PMID- 22580605
TI  - Inhibition of autophagy and tumor growth in colon cancer by miR-502.
AB  - Autophagy is a catabolic process that allows cellular macromolecules to be broken
      down and recycled as metabolic precursors. The influence of non-coding microRNAs
      in autophagy has not been explored in colon cancer. In this study, we discover a
      novel mechanism of autophagy regulated by hsa-miR-502-5p (miR-502) by suppression
      of Rab1B, a critical mediator of autophagy. A number of other miR-502 suppressed
      mRNA targets (for example, dihydroorotate dehydrogenase) are also identified by
      microarray analysis. Ectopic expression of miR-502 inhibited autophagy, colon
      cancer cell growth and cell-cycle progression of colon cancer cells in vitro. miR
      502 also inhibited in-vivo colon cancer growth in a mouse tumor xenografts model.
      In addition, the expression of miR-502 was regulated by p53 via a negative
      feedback regulatory mechanism. The expression of miR-502 was downregulated in
      colon cancer patient specimens compared with the paired normal control samples.
      These results suggest that miR-502 may function as a potential tumor suppressor
      and therefore be a novel candidate for developing miR-502-based therapeutic
      strategies.

PMID- 22580607
TI  - The genesis and unique properties of the lymphovascular tumor embolus are because
      of calpain-regulated proteolysis of E-cadherin.
AB  - The genesis and unique properties of the lymphovascular tumor embolus are poorly
      understood largely because of the absence of an experimental model that
      specifically reflects this important step of tumor progression. The
      lymphovascular tumor embolus is a blastocyst-like structure resistant to
      chemotherapy, efficient at metastasis and overexpressing E-cadherin (E-cad).
      Conventional dogma has regarded E-cad as a metastasis-suppressor gene involved in
      epithelial-mesenchymal transition. However, within the lymphovascular embolus, E
      cad and its proteolytic processing by calpain and other proteases have a dominant
      oncogenic rather than suppressive role in metastasis formation and tumor cell
      survival. Studies using a human xenograft model of inflammatory breast cancer,
      MARY-X, demonstrated the equivalence of xenograft-generated spheroids with
      lymphovascular emboli in vivo with both structures demonstrating E-cad
      overexpression and specific proteolytic processing. Western blot revealed full
      length (FL) E-cad (120 kDa) and four fragments: E-cad/NTF1 (100 kDa), E-cad/NTF2
      (95 kDa), E-cad/NTF3 (85 kDa) and E-cad/NTF4 (80 kDa). Compared with MARY-X, only
      E-cad/NTF1 was present in the spheroids. E-cad/NTF1 was produced by calpain, E
      cad/NTF2 by gamma-secretase and E-cad/NTF3 by a matrix metalloproteinase (MMP).
      Spheroidgenesis and lymphovascular emboli formation are the direct result of
      calpain-mediated cleavage of E-cad and the generation of E-cad/NTF1 from membrane
      associated E-cad rather than the de novo presence of either E-cad/NTF1 or E
      cad/CTF1. E-cad/NTF1 retained the p120ctn-binding site but lost both the beta
      catenin and alpha-binding sites, facilitating its disassembly from traditional
      cadherin-based adherens junctions and its 360 degrees  distribution around the
      embolus. This calpain-mediated proteolysis of E-cad generates the formation of
      the lymphovascular embolus and is responsible for its unique properties of
      increased homotypic adhesion, apoptosis resistance and budding.

PMID- 22580606
TI  - LASS2 enhances chemosensitivity of breast cancer by counteracting acidic tumor
      microenvironment through inhibiting activity of V-ATPase proton pump.
AB  - A main obstacle to overcome during the treatment of tumors is drug resistance to
      chemotherapy; emerging studies indicate that a key factor contributing to this
      problem is the acidic tumor microenvironment. Here, we found that LASS2
      expression was significantly lower in drug-resistant Michigan Cancer Foundation
      7/adriamycin (MCF-7/ADR) human breast cancer cells than the drug-sensitive MCF-7
      cells, and low expression of LASS2 was associated with poor prognosis in patients
      with breast cancer. Our results showed that the overexpression of LASS2 in MCF
      7/ADR cells increased the chemosensitivity to multiple chemotherapeutic agents,
      including doxorubicin (Dox), whereas LASS2 knockdown in MCF-7 cells decreased the
      chemosensitivity. Cell-cycle analysis revealed a corresponding increase in
      apoptosis in the LASS2-overexpressing cells following Dox exposure, showing that
      the overexpression of LASS2 increased the susceptibility to Dox cytotoxicity.
      This effect was mediated by a significant increase in pHe (extracellular pH) and
      lysosomal pH, and more Dox entered the cells and stayed in the nuclei of cells.
      In nude mice, the combination of LASS2 overexpression and Dox significantly
      inhibited the growth of xenografts. Our findings suggest that LASS2 is involved
      in chemotherapeutic outcomes and low LASS2 expression may predict
      chemoresistance.

PMID- 22580608
TI  - Expression of Id proteins is regulated by the Bcl-3 proto-oncogene in prostate
      cancer.
AB  - B-cell leukemia 3 (Bcl-3) is a member of the inhibitor of kappaB family, which
      regulates a wide range of biological processes by functioning as a
      transcriptional activator or as a repressor of target genes. As high levels of
      Bcl-3 expression and activation have been detected in different types of human
      cancer, Bcl-3 has been labeled a proto-oncogene. Our study uncovered a markedly
      upregulated Bcl-3 expression in human prostate cancer (PCa), where inflammatory
      cell infiltration was observed. Elevated Bcl-3 expression in PCa was dependent on
      the proinflammatory cytokine interleukin-6-mediated STAT3 activation. Microarray
      analyses, using Bcl-3 knockdown in PCa cells, identified the inhibitor of DNA
      binding (Id) family of helix-loop-helix proteins as potential Bcl-3-regulated
      genes. Bcl-3 knockdown reduced the abundance of Id-1 and Id-2 proteins and
      boosted PCa cells to be more receptive to undergoing apoptosis following
      treatment with anticancer drug. Our data imply that inactivation of Bcl-3 may
      lead to sensitization of cancer cells to chemotherapeutic drug-induced apoptosis,
      thus suggesting a potential therapeutic strategy in PCa treatment.

PMID- 22580609
TI  - The human Lgl polarity gene, Hugl-2, induces MET and suppresses Snail
      tumorigenesis.
AB  - Lethal giant larvae proteins have key roles in regulating polarity in a variety
      of cell types and function as tumour suppressors. A transcriptional programme
      initiated by aberrant Snail expression transforms epithelial cells to potentially
      aggressive cancer cells. Although progress in defining the molecular determinants
      of this programme has been made, we have little knowledge as to how the Snail
      induced phenotype can be suppressed. In our studies we identified the human
      lethal giant larvae homologue 2, Hugl-2, (Llgl2/Lgl2) polarity gene as
      downregulated by Snail. Snail binds E-boxes in the Hugl-2 promoter and represses
      Hugl-2 expression, whereas removal of the E-boxes releases Hugl-2 from Snail
      repression. We demonstrate that inducing Hugl-2 in cells with constitutive Snail
      expression reverses the phenotype including changes in morphology, motility,
      tumour growth and dissemination in vivo, and expression of epithelial markers.
      Hugl-2 expression reduced the nuclear localization of Snail and thus binding of
      Snail to its target promoters. Our results placing Hugl-2 within the Snail
      network as well as its ability to suppress Snail carcinogenesis identifies Hugl-2
      as a target molecule driving cascades, which may have preventative and
      therapeutic promise to minimize cancer progression.

PMID- 22580610
TI  - miR-34a functions as a tumor suppressor modulating EGFR in glioblastoma
      multiforme.
AB  - Chromosome 1p36.23 is frequently deleted in glioblastoma multiforme (GBM). miR
      34a localizes in this region. Our experiments found that miR-34a was often
      deleted and epidermal growth factor receptor (EGFR) was frequently amplified in
      genomic DNA of 55 GBMs using single-nucleotide polymorphism DNA microarray.
      Notably, we found that the mean survival time was significantly shortened for
      patients whose GBMs had both EGFR amplification and miR-34a deletion. Expression
      of miR-34a was significantly lower in GBM samples compared with normal brain
      tissue. Forced expression of miR-34a in GBM cells decreased their ability to
      migrate and profoundly decreased their levels of cyclin-A1, -B1, -D1, and -D3, as
      well as cyclin-dependent kinase and increased expression of cyclin kinase
      inhibitor proteins (p21, p27). Also, human GBM cells (U251) stable overexpressing
      mir-34a formed smaller tumors when growing as xenografts in immunodeficient mice
      compared with wild-type U251 GBM cells. Furthermore, the protein expression of
      EGFR decreased in the cells with forced overexpression of miR-34a. Additional
      studies showed that mir-34a targeted Yin Yang-1 (YY1) and YY1 is a transcription
      factor that can stimulate the expression of EGFR. Thus, our data suggest that miR
      34a acts as a tumor suppressor by inhibiting growth of GBM cells in vitro and in
      vivo associated with moderating the expression of cell-cycle proteins and EGFR.
      Moreover, we discovered for the first time that both deletion of miR-34a and
      amplification of EGFR were associated with significantly decreased overall
      survival of GBM patients.

PMID- 22580611
TI  - PGE2 promotes renal carcinoma cell invasion through activated RalA.
AB  - Incidence of kidney cancer is on the rise, and a better understanding of
      molecular mechanisms involved in the cancer invasion and metastasis is required
      for the development of curative therapeutics. In this study, we report that the
      proinflammatory cytokine prostaglandin E2 (PGE2) induces the malignant SN12C, but
      not benign HK2 kidney cell invasion. The PGE2 increases SN12C cell invasion
      through a signal pathway that encompasses EP2 and EP4, Akt, small GTPase RalA and
      Ral.GTP inactivator RGC2. The results support the idea that targeted interference
      of EP2/EP4 signal to RalA.GTP may provide benefit to patients diagnosed with
      advanced kidney cancer.

PMID- 22580614
TI  - Endoplasmic reticulum stress triggers autophagy in malignant glioma cells
      undergoing cyclosporine a-induced cell death.
AB  - Autophagy is a conserved, self-digestion process that is activated in response to
      nutrient limitation but acting also as an alternative death mechanism under
      certain conditions. It is accompanied by the progressive formation of vesicle
      structures from autophagosomes to autophagolysosomes orchestrated by autophagy
      effectors (Atg proteins) and modulators (that is, mTOR-mammalian target of
      rapamycin as a negative regulator). Malignant gliomas are highly resistant to
      current therapies that induce apoptosis, thus induction of the alternative cell
      death is an attractive strategy. We demonstrate that cyclosporine A (CsA, an
      immunophilin/calcineurin inhibitor) induces cell death with some apoptotic
      features but also accompanied by the appearance of numerous cytoplasmic vacuoles,
      immunostained for endoplasmic reticulum (ER) and autophagy markers. The induction
      of ER stress in glioma cells by CsA was evidenced by detection of unfolded
      protein response activation (phosphorylation of PERK, accumulation of IRE1alpha)
      and accumulation of ER stress-associated proteins (BIP and CHOP). Formation of
      the acidic vesicular organelles, increase of autophagic vacuoles, GFP-LC3
      punctation (microtubule-associated protein light chain 3) and LC3-II accumulation
      upon CsA treatment confirmed activation of autophagy. Decrease of phosphorylation
      of 4E-BP1, p70S6K1 and its downstream target S6 ribosomal protein demonstrate
      inhibition of mTOR signaling by CsA. Salubrinal and silencing of PERK and
      IRE1alpha partially blocked CsA-induced accumulation of LC3-II. It suggests that
      ER stress precedes CsA-induced autophagy. Surprisingly, silencing of autophagy
      effectors ULK1, Atg5 or Atg7 increased the level of active caspases 3, 7 and PARP
      degradation in CsA-treated cells. Our results demonstrate that CsA induces both
      apoptosis and autophagy in malignant glioma cells via induction of ER stress and
      inhibition of mTOR/p70S6K1 pathway, however autophagy is cytoprotective in this
      context.

PMID- 22580612
TI  - MUC1-C oncoprotein as a target in breast cancer: activation of signaling pathways
      and therapeutic approaches.
AB  - Mucin 1 (MUC1) is a heterodimeric protein formed by two subunits that is
      aberrantly overexpressed in human breast cancer and other cancers. Historically,
      much of the early work on MUC1 focused on the shed mucin subunit. However, more
      recent studies have been directed at the transmembrane MUC1-C-terminal subunit
      (MUC1-C) that functions as an oncoprotein. MUC1-C interacts with EGFR (epidermal
      growth factor receptor), ErbB2 and other receptor tyrosine kinases at the cell
      membrane and contributes to activation of the PI3K?AKT and mitogen-activated
      protein kinase kinase (MEK)?extracellular signal-regulated kinase (ERK) pathways.
      MUC1-C also localizes to the nucleus where it activates the Wnt/beta-catenin,
      signal transducer and activator of transcription (STAT) and NF (nuclear factor)
      kappaB RelA pathways. These findings and the demonstration that MUC1-C is a
      druggable target have provided the experimental basis for designing agents that
      block MUC1-C function. Notably, inhibitors of the MUC1-C subunit have been
      developed that directly block its oncogenic function and induce death of breast
      cancer cells in vitro and in xenograft models. On the basis of these findings, a
      first-in-class MUC1-C inhibitor has entered phase I evaluation as a potential
      agent for the treatment of patients with breast cancers who express this
      oncoprotein.

PMID- 22580613
TI  - On the TRAIL to successful cancer therapy? Predicting and counteracting
      resistance against TRAIL-based therapeutics.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and agonistic
      antibodies against TRAIL death receptors (DR) kill tumor cells while causing
      virtually no damage to normal cells. Several novel drugs targeting TRAIL
      receptors are currently in clinical trials. However, TRAIL resistance is a common
      obstacle in TRAIL-based therapy and limits the efficiency of these drugs. In this
      review article we discuss different mechanisms of TRAIL resistance, and how they
      can be predicted and therapeutically circumvented. In addition, we provide a
      brief overview of all TRAIL-based clinical trials conducted so far. It is
      apparent that although the effects of TRAIL therapy are disappointingly modest
      overall, a small subset of patients responds very well to TRAIL. We argue that
      the true potential of targeting TRAIL DRs in cancer can only be reached when we
      find efficient ways to select for those patients that are most likely to benefit
      from the treatment. To achieve this, it is crucial to identify biomarkers that
      can help us predict TRAIL sensitivity.

PMID- 22580615
TI  - Grosmannia and Leptographium spp. associated with conifer-infesting bark beetles
      in Finland and Russia, including Leptographium taigense sp. nov.
AB  - Species of Grosmannia with Leptographium anamorphs include important forest
      pathogens and agents of blue stain in timber. They are commonly found in
      association with forest pests, such as bark beetles. During a survey of
      ophiostomatoid fungi in eastern parts of Finland and neighboring Russia, species
      belonging to the genus Grosmannia were isolated from 12 different bark beetle
      species infesting Picea abies and Pinus sylvestris, the most economically
      important conifers in the region. Identification of these fungi was based on
      morphology, DNA sequence comparisons for three gene regions and phylogenetic
      analyses. A total of ten taxa were identified. These belonged to six different
      species complexes in Grosmannia. The phylogenetic analyses provided an
      opportunity to redefine the G. galeiformis-, L. procerum-, L. lundbergii-, G.
      piceiperda-, G. olivacea- and G. penicillata-complexes, and to consider the
      species emerging from the survey within the context of these complexes. The
      species included G. galeiformis, G. olivacea, L. chlamydatum, L. lundbergii, L.
      truncatum and a novel taxon, described here as L. taigense sp. nov. In addition,
      species closely related to G. cucullata, G. olivaceapini comb. nov., G.
      piceiperda and L. procerum were isolated but their identity could not be
      resolved. The overall results indicate that the diversity of Grosmannia species
      in the boreal forests remains poorly understood and that further studies are
      needed to clarify the status of several species or species complexes.

PMID- 22580616
TI  - Is uvulopalatopharyngoplasty still an option for the treatment of obstructive
      sleep apnea?
AB  - Uvulopalatopharyngoplasty (UPPP) has been widely described as a surgical option
      for the treatment of obstructive sleep apnea syndrome. Several studies have
      demonstrated variable success rates, and different criteria have been used to
      define success of surgery. The aim of the present study was to assess the
      efficiency of UPPP by polysomnography and to correlate it to the clinical
      findings. Also, we correlated to the various studies dealing with this topic,
      considering the different criteria adopted in each of this. Sixty-four patients
      were included in the study. The efficiency of surgery for UPPP was analyzed to
      the variables such as body mass index, age, preoperative polysomnography results
      and follow-up period. Based on the criteria for postoperative cure, the success
      rate was 44 %. Younger patients presented a better success rate than older ones.
      No other correlation was found between clinical findings and UPPP success. UPPP
      can be curative in some patients, but combination with other treatment modalities
      must be considered. This should be mentioned to the patients, since in many cases
      the sites of airway collapse may be multiple and no clinical aspect (except for
      age) is indicative of good prognosis.

PMID- 22580617
TI  - Objective measures of vestibular function during an acute vertigo attack in a
      very young child.

PMID- 22580618
TI  - Prognostic significance of nodal ratio in cutaneous squamous cell carcinoma of
      the head and neck.
AB  - The TNM classification is not specific for head and neck skin cancer and makes no
      allowance for disease extent. Studies have shown that the relative number of
      metastatic-to-examined lymph nodes, termed the Nodal ratio, is a reliable
      independent prognosticator in several types of cancer. The study was designed as
      a retrospective analysis in a university affiliated tertiary care center setting.
      The files of all patients (n = 71) with cutaneous head and neck squamous cell
      carcinoma and regional lymph node metastasis who attended a tertiary medical
      center between 1990 and 2008 were reviewed for clinical variables and outcome,
      and Nodal ratio was calculated. Data were analyzed for impact on survival. On
      multivariate analysis Nodal ratio and age were found to be significant predictors
      of overall survival. The N-ratio was the only significant predictor of disease
      specific survival. Age, type of treatment (selective/modified neck dissection),
      pathologic N stage, and radiotherapy had no effect. The Nodal ratio is a
      potentially valuable prognostic index in cutaneous squamous cell carcinoma. The
      minimal number of nodes that need to be excised has to be determined.

PMID- 22580619
TI  - Optical coherence tomography for biofilm detection in chronic rhinosinusitis with
      nasal polyposis.
AB  - Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a multifactorial disease
      that seems to be associated with the presence of microbial biofilms and
      corresponding subepithelial inflammatory reactions. Optical coherence tomography
      (OCT) might be applied to detect bacterial and fungal biofilms in patients with
      CRSwNP. A total of 27 patients with CRSwNP undergoing endoscopic sinus surgery
      (ESS) were analyzed. The negative control group consisted of six patients
      undergoing septoplasty for nasal obstruction without CRSwNP. The nasal polyps and
      inferior turbinate mucosa specimens applied as negative controls were processed
      to OCT analysis and H.E. and Gram staining. Biofilm was detected in 22 of 27
      patients (81.5 %) with CRSwNP and in none of six negative controls. In our
      series, OCT scan showed an obvious association with the findings of H.E. and Gram
      staining and was allocated to be a good predictor of biofilm existence. On OCT
      images, biofilms were displayed as distinct superficial layers with high optical
      density. It was found that microscopic architecture of biofilms was strongly
      associated with the integrity of nasal mucosa and to the cellular pattern of
      subepithelial inflammatory reaction. This study confirmed the presence of
      microbial biofilms in patients with CRSwNP according to OCT scans and
      histological analysis. Since biofilms may affect the severity and recurrence rate
      of CRS treated by ESS they should be detected preoperatively. In conclusion,
      single application of OCT analysis or combination with conventional histological
      protocols provides a robust and reliable method for the detection of bacterial
      and fungal biofilms in CRSwNP. Level of evidence 3b, individual case-control
      study.

PMID- 22580620
TI  - Alzheimer's disease and type 2 diabetes: the association study of polymorphisms
      in tumor necrosis factor-alpha and apolipoprotein E genes.
AB  - Type 2 diabetes (T2D) and Alzheimer's disease (AD) are two progressive disorders
      with high prevalence worldwide. Polymorphisms in tumor necrosis factor-alpha (TNF
      alpha) and apolipoprotein E (ApoE) genes might be associated with both T2D and
      AD, representing possible genetic markers for the development of the AD in
      subjects with T2D. The aim was to determine ApoE and G-308A TNF-alpha gene
      polymorphisms in unrelated Croatian Caucasians: 207 patients with sporadic AD,
      196 T2D patients and 456 healthy controls. Patients with AD had higher frequency
      of ApoE4 allele compared to T2D patients and controls. The significant
      association, observed between ApoE2 allele and T2D, disappeared after the data
      were adjusted for age and sex. The genotype or allele frequencies of G-308A TNF
      alpha gene polymorphism were similar among the patients with AD, T2D and healthy
      controls. In conclusion, these results do not support the hypothesis that the A
      allele of G-308A TNF-alpha gene polymorphism is associated either with AD or T2D.
      Our data confirm the association between the ApoE4 allele and AD, and point out
      the E2 allele of ApoE gene as the possible risk factor for T2D.

PMID- 22580621
TI  - Arsenic-induced health crisis in peri-urban Moyna and Ardebok villages, West
      Bengal, India: an exposure assessment study.
AB  - Drinking of arsenic (As)-contaminated groundwater has adverse effects on health
      of millions of people worldwide. This study aimed to determine the degree of
      severity of As exposure from drinking water in peri-urban Moyna and Ardebok
      villages, West Bengal, India. Arsenic concentrations in hair, nail and urine samp
      les of the individuals were determined. Arsenical dermatosis, keratosis and
      melanosis were investigated through medical evaluation. We have evaluated the
      association between As exposure from drinking water, and keratosis and melanosis
      outcomes. The results showed that 82.7 % of the sampled tube wells contain As
      concentrations above 10 MUg/L, while 57.7 % contain As concentrations above 50
      MUg/L. The hair, nail and urine As concentrations were positively correlated with
      As concentrations in drinking water. In our study population, we observed a
      strong association between As concentrations ranging 51-99 MUg/L and keratosis
      and melanosis outcomes, although the probability decreases at higher
      concentration ranges perhaps due to switching away from the use of As
      contaminated tube wells for drinking and cooking purposes. High As concentrations
      in hair, nail and urine were observed to be associated with the age of the study
      population. The level of As concentrations in hair, nail and urine samples of the
      study population indicated the degree of severity of As exposure in the study
      region.

PMID- 22580622
TI  - The effects of siRNA against RPL22 on ET-1-induced proliferation of human
      pulmonary arterial smooth muscle cells.
AB  - The aim of this study was to investigate the effects of small interference RNA
      (siRNA) against ribosomal protein L22 (RPL22) on ET-1-induced proliferation of
      human pulmonary arterial smooth muscle cells (HPASMCs). HPASMCs were transfected
      with siRNA against RPL22, incubated in smooth muscle cell culture medium (SMCM)
      and ET-1. RPL22 gene expression and protein levels of HPASMCs were measured by
      real-time PCR and western blotting, respectively. PCNA, CCK-8
      immunohistochemistry and flow cytometry analysis were used to evaluate HPASMC
      proliferation. Cyclin D1 (CCND1) expression was also assayed. Following
      transfection with siRNA against RPL22, RPL22 expression was significantly
      inhibited in the control and ET-1 groups. HPASMC proliferation was significantly
      suppressed by transfection with siRNA against RPL22. Moreover, CCND1 was also
      downregulated by inhibiting RPL22 expression. In conclusion, these data suggest
      that inhibition of RPL22 expression can suppress HPASMC proliferation and CCND1
      expression. The effects of siRNA against RPL22 on HPASMC proliferation are
      considered to be mediated through inhibition of CCND1 expression.

PMID- 22580624
TI  - Is "teach-back" associated with knowledge retention and hospital readmission in
      hospitalized heart failure patients?
AB  - BACKGROUND: Heart failure (HF) is a chronic and costly condition that affects
      approximately 5.8 million people in the United States, with an additional 670,000
      diagnosed yearly. With high 30-day hospital readmission rates, the importance of
      determining effective means of preventing readmissions is imperative. Despite
      published guidelines emphasizing the importance of education in preventing
      readmissions, the most effective means of educating hospitalized patients with HF
      about their self-care remains unknown. OBJECTIVE: The aim of this study was to
      determine if hospitalized HF patients educated with the teach-back method retain
      self-care educational information and whether it is associated with fewer
      hospital readmissions. METHODS: A prospective cohort study design included 276
      patients older than 65 years hospitalized with HF over a 13-month period.
      Patients were educated and evaluated using the teach-back method as part of usual
      care. Data on ability to recall educational information while hospitalized and
      during follow-up approximately 7 days after hospital discharge were collected.
      Readmissions were confirmed through follow-up telephone calls and review of
      medical records. RESULTS: Patients correctly answered 3 of 4, or 75%, of self
      care teach-back questions 84.4% of the time while hospitalized and 77.1% of the
      time during follow-up telephone call. Greater time spent teaching was
      significantly associated with correctly answered questions (P < .001). Patients
      who answered teach-back questions correctly while hospitalized and during follow
      up had nonsignificant (P = .775 and .609) reductions in all-cause 30-day hospital
      readmission rates, but a trend toward significance (P = .15) was found in
      patients who had readmissions for HF. CONCLUSIONS: The teach-back method is an
      effective method used to educate and assess learning. Patients educated longer
      retained significantly more information than did patients with briefer teaching.
      Correctly answered HF-specific teach-back questions were not associated with
      reductions in 30-day hospital readmission rates. Future studies that include
      patients randomized to receive usual care or teach-back education to compare
      readmissions and knowledge acquisition would provide further comparison of teach
      back effectiveness.

PMID- 22580625
TI  - To be under control: a qualitative study of patients' experiences living with the
      diagnosis of abdominal aortic aneurysm.
AB  - BACKGROUND: Abdominal aortic aneurysm can be treated using 3 different methods:
      open repair, endovascular aortic repair, or conservative treatment with regular
      monitoring and postponement of surgery until the aneurysm is greater than 55 mm.
      Conservative treatment entails living with the knowledge that an aneurysm is
      present while undergoing annual outpatient follow-up. AIM: This study describes
      patients' experiences of living with the knowledge that they have an aneurysm for
      which they are receiving conservative treatment. METHODS: A qualitative,
      phenomenological-hermeneutic approach was used. Interviews were conducted between
      April 2007 and December 2008 with 10 patients diagnosed with abdominal aortic
      aneurysm less than 55 mm. The interpretation and analysis process involved 3
      steps: (1) naive reading and understanding, (2) structural analysis, and (3)
      comprehensive understanding. FINDINGS: Five themes based on subthemes were
      identified: (a) sudden knowledge of a hitherto undetected condition, (b) putting
      your life in someone else's hands, (c) waiting in limbo-feeling secure despite
      concerns, (d) life is at stake, and (e) feeling obliged not to cause worry.
      CONCLUSION: Living with a diagnosis of abdominal aortic aneurysm implies
      awareness of having an invisible, life-threatening disease and a sense of being
      subjected to suffering. We found that patients searched for answers about how to
      influence the growth of the aneurysm in their everyday life. They avoided
      thoughts about the aneurysm and struggled to live life as usual.

PMID- 22580623
TI  - Methods for estimating the site of origin of locoregional recurrence in head and
      neck squamous cell carcinoma.
AB  - PURPOSE: Methods to estimate the likely origin of recurrences after radiation
      therapy for head and neck squamous cell carcinoma are compared. METHODS AND
      MATERIALS: A total of 25 patients meeting the following inclusion criteria were
      randomly selected: curatively intended intensity-modulated radiotherapy planned
      on a positron emission tomography-computed tomography (PET/CT) scan during the
      period 2005-2009; squamous cell carcinoma in the oral cavity, pharynx or larynx;
      complete clinical response followed by locoregional recurrence; and a CT scan at
      recurrence before any salvage therapy. Exclusion criteria were previous cancer in
      the area, surgery prior to radiotherapy, or a synchronous cancer. Three methods
      of estimating focal points of recurrence origin and two volume overlap methods
      assigning the recurrences to the most central target volumes encompassing at
      least 50% or 95% of the recurrence volumes were tested. Treatment planning and
      recurrence scans were rigid and deformable co-registered in order to transfer
      focal points to the treatment planning scan. Double determinations of all
      volumes, points, and co-registrations were made. RESULTS: The volume overlap
      methods assigned the recurrences to significantly more peripheral target volumes
      than focal methods (p < 0.0001 for all comparisons of 95% overlap vs. focal
      methods, p < 0.028 for all comparisons of 50% overlap vs. focal methods).
      Repeated registrations of the same point had higher reproducibility with
      deformable registration than with rigid registration (median distance 0.31 vs.
      0.35 cm, p = 0.015). No significant differences were observed among the focal
      methods. CONCLUSION: Significant differences between methods were found which may
      affect strategies to improve radiotherapy based on pattern of failure analyses.

PMID- 22580626
TI  - Nurse-led group visits support shared decision making in stable coronary artery
      disease.
AB  - OBJECTIVE: The aim of this study was to develop and evaluate a nurse-led
      educational group visit (GV) as part of a multifaceted intervention, shared
      decision making (SDM) guidance reminders in practice, to prompt SDM in primary
      care about angiography in stable coronary artery disease. METHODS: A process
      evaluation designed to test the feasibility of a nurse-led educational GV was
      conducted. The evaluation used retrospective pre-post surveys. RESULTS: Nurse-led
      GV was well received and logistically feasible. Patients gained knowledge of
      options and confidence in doing SDM with providers. However, recruitment at the
      point of the educational GV was below the threshold of 12 patients per group that
      would support sustaining this approach in fee-for-service clinical practice.
      CONCLUSIONS: Nurse-led GV can produce gains in knowledge and confidence required
      for patients to participate in SDM. However, the constraints of time and
      personnel required to bring groups of patients together require new approaches.
      Future development will focus on adapting the content of the GV for SDM as an
      electronic teaching module associated with integrated personal health records.

PMID- 22580627
TI  - Disease-specific quality of life-patient acceptance: racial and gender
      differences in patients with implantable cardioverter defibrillators.
AB  - BACKGROUND: Despite its established effectiveness, living with an implantable
      cardioverter defibrillator (ICD) is associated with ongoing physical and
      psychosocial distress. Little is known about which factors impact the patients'
      adjustment to living with the device and whether there are racial or gender
      differences related to these factors. The purpose of this study was to
      investigate factors (demographic, clinical, psychosocial, and religiosity)
      related to patients' ICD acceptance and to examine racial and gender differences
      in ICD acceptance. METHODS: A total of 101 ICD patients (mean age, 65 +/- 12.8
      years, 34% female, 42% African American [AA]) seen in a cardiology clinic between
      January and August 2010 completed the Florida Patient Acceptance Survey (FPAS),
      Florida shock anxiety scale, ENRICHD social support instrument, hospital anxiety
      and depression scale, Hoge Religiosity Scale, and a demographic sheet during
      their clinic visit. RESULTS: All multiple-item scales demonstrated good internal
      consistency reliability, with Cronbach alpha values ranging from .77 to .89.
      Overall patient acceptance of the ICD was high, with an average FPAS acceptance
      score of 80.9 on the 0-to-100 point scale. The FPAS subscale scores indicated
      that the group was very positive about the benefits of having the device (mean,
      90.3) and had few body image concerns (mean, 10.6), low device-related distress
      (mean, 15.6), and moderate return to function scores (mean, 63.0). White ICD
      participants were more accepting of their device than AA ICD patients were,
      scoring statistically significantly higher than AA patients on total patient
      acceptance and return to function and significantly lower than AA patients on
      device-related distress and shock anxiety. Controlling for ethnicity (beta = .10,
      P = .15), age (beta = .01, P = .90), and number of comorbidities (beta = .19, P =
      .003) in a hierarchical multiple regression, shock anxiety (beta = .31, P <
      .001), knowledge of the device (beta = .23, P = .001), social support (beta =
      .13, P = .08), Hospital Anxiety and Depression Scale anxiety (beta = .06, P =
      .51) and depression (beta = .25, P = .01), and importance of religion (beta =
      .17, P = .01) explained 46.8% of the variance in FPAS scores. CONCLUSIONS:
      Although overall patient acceptance was high, AAs in the study had statistically
      significant lower mean total Florida Patient Acceptance Scale scores and Return
      to Function scores than whites did and higher Device-Related Distress scores. The
      strongest predictors of patient acceptance for the total group were shock
      anxiety, depressive symptoms, and device knowledge. African Americans had
      significantly lower device knowledge scores and higher shock anxiety scores than
      whites did. These findings suggest that ICD patients, especially AA ICD patients,
      may require education and psychosocial measures to enhance acceptance of their
      device. This study supports a holistic and culturally sensitive approach to
      focused clinical and psychological assessment and interventions for those living
      with this life-saving technology.

PMID- 22580628
TI  - Association of comorbidities with home care service utilization of patients with
      heart failure while receiving telehealth.
AB  - BACKGROUND: Comorbidities adversely impact heart failure (HF) outcomes.
      Telehealth can assist healthcare providers, especially nurses, in guiding their
      patients to follow the HF regimen. However, factors, including comorbidity
      patterns, that act in combination with telehealth to reduce home care nursing
      utilization are still unclear. PURPOSE: The purpose of this article was to
      examine the association of the comorbidity characteristics of HF patients with
      nursing utilization along with withdrawal from telehealth service during an
      episode of tele-home care. METHODOLOGY: A descriptive, correlational study design
      using retrospective chart review was used. The sample comprised Medicare patients
      admitted to a New England home care agency who had HF as a diagnosis and had used
      telehealth from 2008 to 2010. The electronic documentation at the home care
      agency served as the data source, which included Outcome and Assessment
      Information Set data of patients with HF. Logistic and multiple regression
      analyses were used to analyze data. RESULTS: The sample consisted of 403
      participants, of whom 70% were older than 75 years, 55% were female, and 94% were
      white. Comorbidities averaged 5.19 (SD, 1.92), ranging from 1 to 11, and nearly
      40% of the participants had 5 or more comorbidities. The mean (SD) nursing
      contacts in the sample was 9.9 (4.7), ranging from 1 to 26, and 52 (12.7%)
      patients withdrew from telehealth service. For patients with HF on telehealth,
      comorbidity characteristics of anemia, anxiety, musculoskeletal, and depression
      were significantly associated with nursing utilization patterns, and renal
      failure, cancer, and depression comorbidities were significantly associated with
      withdrawal from telehealth service. CLINICAL IMPLICATIONS: Knowledge of the
      association of comorbidity characteristics with the home care service utilization
      patterns of patients with HF on telehealth can assist the home health nurse to
      develop a tailored care plan that attains optimal patient outcomes. Knowledge of
      such associations would also focus home care resources, avoiding redundancy of
      resource utilization in this era of strained healthcare resources.

PMID- 22580629
TI  - Patterns of symptom recognition, interpretation, and response in heart failure
      patients: an integrative review.
AB  - BACKGROUND: Heart failure (HF) is a chronic illness affecting more than 5 million
      Americans, and it continues to lead healthcare-related expenditures in the United
      States. Hospitalization rates remain high and are caused by many factors,
      including poor self-care behaviors. Self-care research is growing, and a
      situation-specific theory for the HF population is now published. Self-care
      management, which is part of self-care, includes a series of responses and
      actions that the individual living with HF assumes in response to a change in
      baseline health. A critical aspect of enacting a self-care management plan is the
      ability to recognize changes in baseline health as being related to HF. PURPOSE:
      This integrative review examined research to date on self-reported patterns of
      symptom recognition, an antecedent to self-care management, and treatment-seeking
      behaviors in HF patients. CONCLUSIONS: Descriptive research strategies were
      predominantly used to examine symptom recognition, interpretation, and response
      in HF patients. Seven studies used retrospective approaches, such as chart review
      or patient recall, to collect data, and 7 studies collected data from the patient
      prospectively. The quantitative portion of 2 mixed-methods study was also
      analyzed. Dyspnea was the most frequently reported symptom across all studies
      reviewed. Dyspnea was characterized in terms of duration and was defined
      inconsistently across studies. In some studies, duration of dyspnea was
      associated with treatment-seeking delays. Elderly patients and newly diagnosed HF
      patients are more likely to delay treatment seeking for onset of symptoms.
      CLINICAL IMPLICATIONS: Research is limited on symptom recognition and treatment
      seeking behaviors in HF patients. Evidence suggests that symptom recognition may
      be impaired in the elderly population. Research studies to date on symptom
      recognition have largely been descriptive; no studies in this review followed
      patients' ability to recognize and respond to symptoms prospectively in their
      home environment. Symptoms may vary and their pattern may influence patients'
      recognition and/or response patterns.

PMID- 22580630
TI  - The relationships among satisfaction with social support, quality of life, and
      survival 5 to 10 years after heart transplantation.
AB  - BACKGROUND: Despite the fact that social support has been found to be important
      to cardiovascular health, there is a paucity of information regarding the
      relationship between social support and outcomes long-term after heart
      transplantation (HT). OBJECTIVES: Therefore, the purposes of our retrospective
      analyses of a prospective, longitudinal study were to examine (1) the
      relationship between satisfaction with social support and post-HT health-related
      quality of life (HRQOL) and survival and (2) whether 2 types of social support
      (emotional and tangible) were predictors of survival and HRQOL. METHODS: Data
      were collected from 555 HT patients over a 5-year period (78% male, 88% white;
      mean age, 53.8 years at time of transplantation) at 4 US medical centers using
      the following instruments: Social Support Index, Quality of Life Index, Heart
      Transplant Stressor Scale, Jalowiec Coping Scale, and medical records review.
      Statistical analyses included t tests, correlations, Kaplan-Meier survival
      actuarials, and linear and multivariable regression. RESULTS: Patients were very
      satisfied with overall social support from 5 to 10 years after HT (0 = very
      satisfied, 1 = very dissatisfied), which was stable across time (P = .74).
      Satisfaction with emotional social support (P = .53) and tangible social support
      (P = .61) also remained stable over time. When stratified into low, medium, and
      high levels of satisfaction, satisfaction with social support was not related to
      survival (P = .24). At 5 years, overall satisfaction with social support was a
      predictor of HRQOL (r = 0.59, P < .0001), and satisfaction with emotional social
      support was a predictor of HRQOL at 10 years after HT (r = 0.66, P < .0001).
      CONCLUSIONS: Patients were very satisfied over time with emotional and tangible
      social support. While social support explained quality of life outcomes, it did
      not predict survival. Knowledge of relationships among social support, stress,
      and outcomes may assist clinicians to address social support needs and resources
      long-term after HT.

PMID- 22580632
TI  - Gender differences in accessory connections location: an Israeli study.
AB  - BACKGROUND: Recent studies have shown that the pathogenesis of accessory
      connections (AC) formation may have a genetic component. OBJECTIVE: The purpose
      of the study was to examine whether AC location differs by gender in a large
      cohort of patients with AC undergoing radiofrequency ablation (RFA) in two
      Israeli electrophysiology (EP) laboratories. METHODS: All consecutive patients
      who underwent RFA of single ACs in Tel Aviv Sourasky Medical Center between 1992
      and 2009 (n = 574) as well as the first consecutive 230 patients who underwent
      RFA in Sheba Medical Center between 1992 and 2001 were included in this study.
      RESULTS: The 804 patients in the two centers included 511 males (63.6 %) and 293
      (36.4 %) females, mean age 34 + 16 years old. The AC was located in the left free
      wall, posteroseptal, right free wall, right anteroseptal, and in other areas in
      57.8, 22.8, 9.3, 7 and 3.1 % of patients, respectively. The anatomical AC
      distribution was similar in the two EP laboratories. A right free wall location
      was more frequent in females (13 %) than in males (7.2 %; p = 0.008). A right
      anteroseptal location was more frequent in males (8.4 %) than in females (4.4 %)
      (p = 0.043). The left free wall and posteroseptal locations were similarly
      encountered in males (58.1 and 23.1 %, respectively) and in females (57.3 and
      22.2 %, respectively). CONCLUSIONS: In our Israeli population, females more
      commonly have right free wall ACs and males more commonly have right anteroseptal
      ACs. These findings support the possible role of a genetic component in the
      pathogenesis of AC formation.

PMID- 22580631
TI  - Aging might augment reactive oxygen species (ROS) formation and affect reactive
      nitrogen species (RNS) level after myocardial ischemia/reperfusion in both humans
      and rats.
AB  - Previous studies indicate aging results in significantly decreased cardiac
      function and increased myocardial apoptosis after myocardial ischemia/reperfusion
      (MI/R) in humans or rats. The underlying mechanisms of aging-exacerbated effects
      remain unknown. Reactive oxygen species (ROS) and reactive nitrogen species (RNS)
      are known to play vital roles in aging-related MI/R injury. Heretofore, the
      effects of aging upon ROS and RNS formation were not investigated in humans,
      which is the focus of the current study. Due to experimental limitations with
      clinical trials, an additional animal experiment was performed. All enrolled
      acute myocardial infarction (AMI) patients received percutaneous coronary
      intervention (PCI) therapy. AMI patients were assigned into two groups: adult
      (age <65, n = 34) and elderly (age >=65, n = 45) AMI patients. Blood samples were
      obtained from all study participants at 24 h and 3 days post-PCI. Plasma/white
      blood cell (WBC) ROS and RNS markers (malondialdehyde (MDA), myeloperoxidase
      (MPO), reduced glutathione (GSH), inducible nitric oxide synthase (iNOS)
      activity, NOx, and nitrotyrosine) were determined. The same markers were
      determined in rat cardiac tissue after 24 h MI/R. Compared to the adult group,
      elderly patients manifested increased plasma MDA and MPO and decreased plasma GSH
      concentrations. No significant differences in plasma NOx or nitrotyrosine
      concentration existed between adult and elderly patients. Furthermore, WBC iNOS
      activity in elderly patients was significantly decreased compared to the adult
      group. The measurement of ROS markers in the rat experiments was consistent and
      supported human study data. Surprisingly, RNS markers (NOx and nitrotyrosine) in
      blood and heart tissue increased from young to middle-aged rats but decreased
      from middle age to old age. Aging augments ROS, which might exacerbate MI/R
      injury. Additionally, our data support aging-induced changes of RNS levels in
      humans and rats in vivo.

PMID- 22580633
TI  - Reuse of infected cardiac rhythm management devices in the same individual.
AB  - PURPOSE: Infected device explantation is increasingly necessary given the rapid
      growth in cardiac rhythm management device (CRMD) implantation in China. However,
      some patients with CRMD infection are unlikely to be capable of paying for a new
      device. Reassuringly, evidence suggests that reuse of cardiac devices can be safe
      and feasible. In this study, we evaluated whether explanted cardiac devices, due
      to infection, can be reimplanted safely within the same individuals. METHODS: All
      patients with CRMD infection between 2007 and 2010 were entered into a computer
      database. From these, patients that had need for CRMD implantation and
      reimplantation of their infected device were analyzed for safety and
      complications. RESULTS: Sixty patients had CRMD implantation after the infected
      device removal, and 44 (73.3 %) patients underwent procedures for reimplantation
      of their infected device. The mean age of the patients was 64.8 +/- 16.5 years,
      and 32 (72.7 %) were male. Indications for device explantation were: pocket
      infection (86.6 %) and endocarditis (11.4 %). The average follow-up was 20.4 +/-
      9.0 months. Endocarditis recurred in one (2.3 %) patient with Brugada syndrome at
      17 months after reimplantation of a refurbished implantable cardioverter
      defibrillator. There were three deaths during the follow-up period secondary to
      myocardial infarction and cerebral vascular accident. No early battery depletion
      or device malfunction was identified during follow-up. CONCLUSIONS: Our data
      emphasize that reimplantation of explanted CRMDs, due to infection, within the
      same individual is feasible, safe, and effective. Reuse of explanted CRMDs is an
      alternative choice for people in developing countries.

PMID- 22580634
TI  - Treatment of renal stones in infants: comparing extracorporeal shock wave
      lithotripsy and mini-percutaneous nephrolithotomy.
AB  - The objective of the study is to compare the efficacy and safety of
      extracorporeal shock wave lithotripsy (ESWL) and mini-percutaneous
      nephrolithotomy (MPCNL) in treating renal stones sizing 15-25 mm in infants <3
      years. Forty-six infants with renal stones sizing 15-30 mm were treated by either
      ESWL (22 renal units in 22 infants) using Dornier compact delta lithotripter or
      MPCNL (25 renal units in 24 infants) using 14F-18F renal access under general
      anesthesia. The operation time, stone-free rate, re-treatment rate, and
      complications between the two groups were compared with the chi(2), Mann-Whitney
      U, and Student's t tests. No significant differences in mean age and stone size
      were observed between the two groups. The 1- and 3-month postoperative stone-free
      rates were 84 and 96% in MPCNL group and were 31.8 and 86.4% in ESWL group. The
      re-treatment and complication rates were significantly higher in ESWL group than
      in MPCNL group (50 vs. 12%, P = 0.004; 16.0 vs. 45.5%, P = 0.028). The stone
      recurrence rate was similar between the two groups. No significant changes of
      serum creatinine (Cr) level and glomerular filtration rate were observed in both
      groups. In conclusion, MPCNL is an effective and feasible alternative monotherapy
      for large renal stones (15-25 mm) in infants, with a higher stone-free rate and a
      lower complication rate when compared with ESWL.

PMID- 22580636
TI  - Management of ejaculatory disorders in infertile men.
AB  - Ejaculatory dysfunction is a highly prevalent clinical condition that may be
      classified along a continuum that ranges from premature ejaculation (PE), through
      retarded or delayed ejaculation (DE), to complete anejaculation (AE). Retrograde
      ejaculation (RE) represents a distinct entity in which ejaculate is expelled
      either partially or completely into the bladder. While DE and PE are significant
      sources of sexual dissatisfaction among men and their partners, patients with
      these disorders retain normal fertility in most cases. Conversely, men with AE
      and RE are unable to deliver sperm into the female genital tract and are
      therefore rendered subfertile. Therefore, in reviewing ejaculatory disorders as
      they relate to fertility, this paper will primarily focus on the diagnosis and
      management of AE and RE. Physiology, diagnostic strategies, pharmacological
      treatments, and procedural interventions relevant to AE and RE are discussed.

PMID- 22580635
TI  - A pilot study of the association between genetic polymorphisms involved in
      estrogen signaling and infant male genital phenotypes.
AB  - Single nucleotide polymorphisms (SNPs) in genes that influence development of the
      male reproductive tract have been associated with male genitourinary
      abnormalities. However, no studies have tested the relationship between SNPs and
      intermediate phenotypes such as anogenital distance (AGD), anoscrotal distance
      (ASD) and penile width (PW). We tested whether 24 common SNPs in eight genes that
      influence male genital development were associated with intermediate phenotypes
      in 106 healthy male infants from the Study for Future Families. We used DNA from
      buccal smears and linear regression models to assess the relationship between
      anogenital measurements and SNP genotypes with adjustment for covariates. We
      found that the rs2077647 G allele, located in the coding region of estrogen
      receptor alpha (ESR1), was associated with a shorter AGD (P=0.02; -7.3 mm, 95%
      confidence interval (CI): -11.6 to -3.1), and the rs10475 T allele, located in
      the 3' untranslated region of activating transcription factor 3 (ATF3), was
      associated with a shorter ASD (-4.3 mm, 95% CI: -7.2 to -1.4), although this
      result was not significant (P=0.07) after controlling for multiple comparisons.
      We observed no association between PW and the SNPs tested. Minor alleles for two
      SNPs in genes that regulate estrogen signaling during male genital development
      were associated with AGD and ASD, although the significance of the association
      was marginal. Our findings suggest that AGD and ASD are influenced by heritable
      factors in genes known to be associated with frank male genital abnormalities
      such as hypospadias and cryptorchidism.

PMID- 22580638
TI  - Combining active immunotherapy with immune checkpoint blockade for the treatment
      of advanced prostate cancer.

PMID- 22580639
TI  - Genetic marker of torsades de pointes risk following myocardial infarction.

PMID- 22580637
TI  - Plasmid-based Survivin shRNA and GRIM-19 carried by attenuated Salmonella
      suppresses tumor cell growth.
AB  - Persistent activation of Survivin and its overexpression contribute to the
      formation, progression and metastasis of several different tumor types.
      Therefore, Survivin is an ideal target for RNA interference mediated-growth
      inhibition. Blockade of Survivin using specific short hairpin RNAs (shRNA) can
      significantly reduce prostate tumor growth. RNA interference does not fully
      ablate target gene expression, owing to the idiosyncrasies associated with shRNAs
      and their targets. To enhance the therapeutic efficacy of Survivin-specific
      shRNA, we employed a combinatorial expression of Survivin-specific shRNA and gene
      associated with retinoid-interferon-induced mortality-19 (GRIM-19). Then, the
      GRIM-19 coding sequences and Survivin-specific shRNAs were used to create a dual
      expression plasmid vector and were carried by an attenuated strain of Salmonella
      enteric serovar typhimurium (S. typhimurium) to treat prostate cancer in vitro
      and in vivo. We found that the co-expressed Survivin-specific shRNA and GRIM-19
      synergistically and more effectively inhibited prostate tumor proliferation and
      survival, when compared with treatment with either single agent alone in vitro
      and in vivo. This study has provided a novel cancer gene therapeutic approach for
      prostate cancer.

PMID- 22580640
TI  - Incorporating intraspecific variation in tests of trait-based community assembly.
AB  - Environmental filtering and niche differentiation are processes proposed to drive
      community assembly, generating nonrandom patterns in community trait
      distributions. Despite the substantial intraspecific trait variation present in
      plant communities, most previous studies of trait-based community assembly have
      used species mean trait values and therefore not accounted for intraspecific
      variation. Using a null model approach, I tested for environmental filtering and
      niche differentiation acting on three key functional traits--vegetative height,
      specific leaf area (SLA), and leaf dry matter content (LDMC)-in old-field plant
      communities. I also examined how accounting for intraspecific variation at the
      among-plot and individual levels affected the detection of nonrandom assembly
      patterns. Tests using fixed species mean trait values provided evidence of
      environmental filtering acting on height and SLA and niche differentiation acting
      on SLA. Including plot-level intraspecific variation increased the strength of
      these patterns, indicating an important role of intraspecific variation in
      community assembly. Tests using individual trait data indicated strong
      environmental filtering acting on all traits, but provided no evidence of niche
      differentiation, although these signals may have been obscured by the effects of
      dispersal limitation and spatial aggregation of conspecific individuals. There
      was also strong evidence of nonrandom assembly of individuals within single
      species, with the strength of environmental filtering varying among species. This
      study demonstrates that, while analyses using fixed species mean trait values can
      provide insights into community assembly processes, accounting for intraspecific
      variation provides a more complete view of communities and the processes driving
      their assembly.

PMID- 22580641
TI  - Facially-selective thymine-thymine photodimerization in TTT triads.
AB  - Irradiation of alkane-linked DNA hairpins possessing TTT steps with flanking
      purine bases yields products identified as the cis-syn (2 + 2) dimers formed
      between the central thymine and its 3'- and 5'-neighbors. Selective formation of
      the 3'-dimer is attributed to ground state conformational effects and electron
      transfer quenching by purine bases.

PMID- 22580642
TI  - Diagnostic yield of capsule endoscopy vs. double-balloon endoscopy for patients
      who have undergone total enteroscopy with obscure gastrointestinal bleeding.
AB  - BACKGROUND/AIMS: The usefulness of capsule endoscopy (CE) and of double-balloon
      endoscopy (DBE) for detection of small-bowel lesions is widely accepted. We
      compared CE- and DBE-based detection of small-bowel lesions in patients with
      obscure gastrointestinal bleeding (OGIB) who underwent total enteroscopy by both
      CE and DBE. METHODOLOGY: One hundred eighteen consecutive patients (70 men, 48
      women; mean age 62.9+/-18.4 years) with OGIB underwent both CE and DBE. CE was
      performed and DBE was then performed within 1 week by both retrograde and
      antegrade approaches. Differences in detection rates were analyzed. RESULTS:
      Overall, small-bowel lesions were detected by CE in 53 patients (44.9%) and by
      DBE in 63 patients (53.4%) (p=0.01); agreement between CE and DBE findings was
      good (kappa statistic=0.76). Total enteroscopy was achieved by both modalities in
      54 patients; CE detected small-bowel lesions in 25 of these patients (46.3%), and
      DBE detected lesions in 28 of these patients (51.9%) (p=0.25); agreement between
      CE and DBE findings was very good (kappa statistic=0.88). CONCLUSIONS: Our data
      support preferential use of noninvasive CE for patients with OGIB and subsequent
      DBE examination in most cases.

PMID- 22580643
TI  - Intraperitoneal and intravenous chemotherapy in peritoneal carcinomatosis.
AB  - BACKGROUND/AIMS: We conducted a phase I trial of IP oxaliplatin and paclitaxel
      with IV paclitaxel and bevacizumab in patients with peritoneal carcinomatosis.
      METHODOLOGY: Patients received IV bevacizumab (2.5mg/kg) over 1 hour (day 1),
      then IV paclitaxel (110 mg/m2) 24-hr-infusion (day 1) and IP oxaliplatin (25-40
      mg/m2) (day 2), and IP paclitaxel (30-60 mg/m2) (day 8 from cycle 2 onwards). A
      '3+3' design was used. RESULTS: Nineteen patients were treated (median age 60
      years; 10 women, 9 men; median number of prior therapies 3). Primary tumors were
      colorectal (n=9), signet ring carcinoma (n=2), gastric (n=2), ovarian (n=2) and
      others (n=4). The maximum tolerated doses (MTD) of IP oxaliplatin and IP
      paclitaxel were 25mg/m2 and 60 mg/ m2, respectively. Nine (47%) patients reported
      no toxicities >grade 2. Two patients receiving IP oxaliplatin 40 mg/m2 and IP
      paclitaxel 60 mg/m2 had dose limiting toxicities (DLT) of grade 3
      diarrhea/dehydration and febrile neutropenia. Toxicities included abdominal pain
      (n=14), nausea (n=10) and constipation (n=7). Of 12 patients restaged at 2
      months, 7 (58%) had stable disease (SD) including 2 (17%) who had SD for >4
      months. CONCLUSIONS: IP paclitaxel and IP oxaliplatin can be given safely at 60
      mg/m2 and 25mg/m2, respectively.

PMID- 22580644
TI  - Prediction of genetic polymorphisms of DNA repair genes XRCC1 and XRCC3 in the
      survival of colorectal cancer receiving chemotherapy in the Chinese population.
AB  - BACKGROUND/AIMS: We aimed to detect the distribution of DNA repair genes XRCC1
      and XRCC3 genotypes in the survival of colorectal cancer patients receiving
      chemotherapy in the Chinese population. METHODOLOGY: The prospective study was
      conducted with 432 cases treated with 5-FU and oxaliplatin as first-line
      chemotherapy. All the patients were followed-up from May 2006 to May 2011 and 168
      patients died during follow-up. XRCC1 and XRCC3 genotype polymorphisms were based
      upon the PCR-CTPP method. RESULTS: It was shown that the XRCC1 Arg399Gln and
      XRCC3 Thr241Met gene polymorphisms were associated with increased death risk of
      colorectal cancer. Individuals carrying XRCC1 Gln/Gln, Thr/Met and Met/Met
      genotypes positively associated with 2.78-, 2.86- and 3.0-fold death risk of
      colorectal cancer. Moreover, the combination of XRCC1 399Gln allele and XRCC3
      241Met allele showed a significantly strong association with death risk of
      colorectal cancer (OR=3.46, 95%CI=1.65- 5.48). CONCLUSIONS: This study is first
      to report that the XRCC1 and XRCC3 gene polymorphisms are useful as a surrogate
      marker of clinical outcome in colorectal cancer with 5-FU/oxaliplatin combination
      chemotherapy in the Chinese population.

PMID- 22580645
TI  - Evaluation of relation of RAD51 and the effect of chemo-radiation therapy for
      advanced rectal cancer.
AB  - BACKGROUND/AIMS: Chemo-radiation therapy (CRT) has been used to improve local
      control and survival in patients with advanced rectal carcinoma. However, a
      significant proportion of patients shows poor response to adjuvant CRT. We thus
      investigated the usefulness of RAD51 expressions as a predictive maker of the CRT
      response. METHODOLOGY: Forty two patients who suffered from lower rectal cancer
      were investigated. All patients received preoperative CRT consisting of TS-1,
      concurrent with 40Gy of pelvic irradiation before having curative radical
      resection. The relationship between pathological responses of the tumors after
      therapy and expression of RAD51 was evaluated by immunostaining of resected
      specimen. RESULTS: Positive expression of RAD51 was observed in 24 of 42 patients
      (57.1%). RAD51 positively expressed in 68.2% (15 of 22 cases) of SD and 42.2% (9
      of 20 cases) of PR and CR. There is a tendency of reverse correlation between
      clinical response and expression of RAD51. Regarding the correlation between
      pathological response and RAD51 expression, positive expression of RAD51 was
      recognized in 75.0% (15 of 20 cases) of Grade 1, 47.1% (8 of 17 cases) of Grade 2
      and 20.0% (1 of 5 cases) of Grade 3. A significant reverse correlation was
      recognized between RAD51 expression and pathological responses. CONCLUSIONS:
      RAD51 expression could be one of the most important predictive factors of
      preoperative CRT for advanced lower rectal cancer.

PMID- 22580646
TI  - Co-treatment of dichloroacetate, omeprazole and tamoxifen exhibited
      synergistically antiproliferative effect on malignant tumors: in vivo experiments
      and a case report.
AB  - BACKGROUND/AIMS: Omeprazole (OPZ) and tamoxifen (TAM) strengthen the effects of
      anticancer drugs and dichloroacetate (DCA) inhibits tumor growth. This study
      assesses the synergistic effects of these drugs. METHODOLOGY: HT1080 human
      fibrosarcoma cells and WI-38 human fibroblasts were used as test and control
      cells, respectively. DCA, OPZ and TAM alone or in combination were applied and
      cells were counted after a one week culture. The combination of these drugs was
      prescribed to a cholangiocarcinoma patient and serum CA19-9 was monitored.
      RESULTS: DCA combined with OPZ and TAM exhibited more potent antitumor activity
      than DCA alone in HT1080 fibrosarcoma cells, but did not influence proliferation
      of WI-38 human fibroblasts. All these drugs induce caspase-dependent cell growth
      inhibition through superoxide production. Since they can be taken orally and have
      been used clinically without major side effects, it was thought that this
      combination therapy would be a readily translated strategy to treat malignant
      tumors. Under the patient's consent these three drugs were prescribed to a 51
      year old female cholangiocarcinoma patient to whom neither gemcitabine+S-1 nor
      adoptive immunotherapy with natural killer cells was effective. Disease
      progression was successfully blocked (the rise of serum CA19-9 value) for three
      months, also confirmed by CT. CONCLUSIONS: Although findings are preliminary,
      this study is a sample of translational research. Since there is no consensus
      regarding treatment strategy of cholangiocarcinoma and chemotherapy has only
      limited efficacy, it is expected that it might open a new possibility of
      treatment.

PMID- 22580647
TI  - Laparoscopic single-branch resection of the pancreas for intraductal papillary
      mucinous neoplasm.
AB  - Although laparoscopic pancreatic resections have become more common, laparoscopic
      minimally invasive and function-preserving pancreatic resections have not been
      widely accepted. Branch-type intraductal papillary mucinous neoplasm (IPMN) has a
      low-grade malignant potential and shows a favorable prognosis. In branch-type
      IPMN, minimal resection techniques with preservation of the pancreatic functional
      reserve have advantages over the more conventional pancreaticoduodenectomy. We
      describe herein laparoscopic single-branch resection of the pancreas for
      branchtype IPMN. This surgical procedure is a novel and an ideal minimally
      invasive method for the resection of branch-type IPMN. In addition, our
      endoscopic nasopancreatic drainage (ENPD) tube-guided technique is useful for
      precise resection of the tumor and for the prevention of pancreatic fistula.

PMID- 22580648
TI  - The efficacy of intraoperative ultrasonography during laparoscopic
      cholecystectomy.
AB  - BACKGROUND/AIMS: Intraoperative ultrasonography (IOUS) has been used to delineate
      anatomy during laparoscopic cholecystectomy (LapC) and screen for common bile
      duct stones (CBDS), however no consensus about its efficacy has been reached in
      Japan. In this study, we compared and evaluated the performance of intraoperative
      cholangiography(IOC) and IOUS during LapC. METHODOLOGY: We evaluated 295 cases of
      cholecystolithiasis that underwent surgery from 2005- 2009 at our hospital.
      Frequency of CBDS and duration of surgery was examined in cases with IOC alone or
      IOC and IOUS in combination. RESULTS: There were 5 cases (1.7%) in which IOUS or
      IOC detected CBDS that had not been detected by preoperative evaluation using
      abdominal CT, abdominal ultrasonography or MRCP. Out of 62 LapC cases involving
      both IOC and IOUS, 60 cases showed the same findings, i.e. no false-negative
      results, indicating that IOUS is a trustworthy examination method. The mean
      duration of surgery involving IOUS alone was 135 minutes while a longer mean time
      of 163 minutes was found for that involving IOC alone or IOC and IOUS in
      combination. CONCLUSIONS: This study shows that IOC can be considered useful as
      it did not produce any false-negative results in screening CBDS and it also
      shortened the operation time. We also found some problems associated with IOC,
      such as small calculi falling within the gallbladder during examination
      procedures and the irradiation of patients and staff.

PMID- 22580649
TI  - Laparoscopic cholecystectomy techniques with special care treatment in acute
      cholecystitis patients regardless of operation timing.
AB  - BACKGROUND/AIMS: The optimal timing for laparoscopic cholecystectomy (LC) in
      acute cholecystitis (AC) remains controversial. In this study, we aggressively
      performed three types of LC techniques in AC patients at different time with our
      care procedure. METHODOLOGY: Forty-three patients with AC were retrospectively
      divided into two groups: Group one (n=16, within 72 hrs at the onset of symptoms)
      and Group two (n=27, beyond 72 hrs after the onset of symptoms). Standard,
      subtotal or prograde cholecystectomy were performed for all cases, depending on
      the fragility of gallbladder wall, difficulty of gallbladder dissection,
      assurance of Calot's triangle and quality of retraction over Hartman pouch.
      RESULTS: There were no statistical differences between both groups with regards
      to age, operation time, length of hospital stay and complications. Gangrenous
      cholecystitis was found in 6.3% of cases in Group one and 26.9% in Group two,
      although not statistically different. Four cases (two in each of groups)
      underwent prograde cholecystectomy and four cases in the group 2 received
      subtotal cholecystectomy; all with longer operation time and length of stay, as
      compared to standard cholecystectomy. None of the 43 patients was converted to
      open procedure. Complications in this study were minor. CONCLUSIONS: LC can be
      safely performed in patients with AC with special care, regardless of the
      duration between the onset of symptoms and operation. In addition to standard
      procedures, subtotal and prograde cholecystectomy could help to manage
      inflammatory gallbladder and obscured Calot's triangle.

PMID- 22580650
TI  - Long-term outcome of surgical treatment for ampullary carcinoma.
AB  - BACKGROUND/AIMS: We aimed to clarify the surgical indication and describe the
      long-term surgical outcome for ampullary carcinoma. METHODOLOGY: The long-term
      outcomes of 23 patients who underwent pancreaticoduodenectomy were
      retrospectively reviewed. The prognostic factors for cancer-specific survival and
      overall survival after surgery were investigated. RESULTS: The cancer-specific 5
      , 10- and 20-year survival rates after resection of the ampullary carcinoma were
      52%, 43% and 43%, respectively, while the corresponding overall survival rates
      were 52%, 32% and 24%, respectively. Ten of the 11 patients with recurrent
      ampullary carcinoma died within 5 years after surgery. Four patients died because
      of pancreatic cancer, colon cancer, old age after curative resection of gastric
      cancer, and pneumonia at later than 5 years after the surgery. The risk factors
      for the short cancer-specific survival period were pancreatic invasion and lymph
      node metastasis, while those for the short overall survival period were
      pancreatic invasion and the tumor grade. CONCLUSIONS: Our study indicates that
      recurrence of ampullary carcinoma within 5 years after its resection, especially
      in patients with pancreatic invasion or lymph node metastasis and development of
      other diseases after more than 5 years after the surgery should be carefully
      investigated.

PMID- 22580651
TI  - Comparative study of gastric emptying and nutritional status after pylorus
      preserving vs. subtotal stomach-preserving pancreaticoduodenectomy.
AB  - BACKGROUND/AIMS: Delayed gastric emptying (DGE) is a specific, worrisome
      complication after pancreaticoduodenectomy (PPPD), whereas subtotal stomach
      preserving pancreaticoduodenectomy (SSPPD) that excises the pylorus ring seems to
      be effective in reducing DGE. This study compared gastric emptying and
      nutritional status between PPPD and SSPPD over 1 year. METHODOLOGY: From June
      2003 to December 2007, 41 patients (PPPD: 33, SSPPD: 8) were enrolled in this
      study to evaluate differences in gastric emptying and nutritional status at 1, 3,
      6, 9 and 12 months after pancreaticoduodenectomy. Gastric emptying was evaluated
      by 13C-acetate breath test. Nutritional status (body weight, serum levels of
      total protein, albumin and total cholesterol) was similarly assessed. RESULTS: At
      1 month, gastric emptying evaluated at T1/2 (half-emptying time) was
      significantly prolonged in the PPPD but not in the SSPPD compared to the
      preoperative level. Thereafter, T1/2 was decreased and showed function
      significantly better preserved at 3, 6 and 12 months after PPPD than after SSPPD.
      Body weight recovery was significantly better at 6 and 12 months after PPPD than
      after SSPPD. Other nutritional parameters were better preserved in the PPPD
      during 1-year follow-up. CONCLUSIONS: PPPD seems to be a more suitable surgical
      procedure than SSPPD in regard to gastric emptying and nutritional status.

PMID- 22580652
TI  - Intrahepatic cholangiojejunostomy (Longmire procedure) for recurrent bilioenteric
      anastomotic stricture with hepatolithiasis.
AB  - Interventional procedure via percutaneous transhepatic route is often performed,
      as an initial treatment, in patients with benign bilioenteric anastomotic
      stricture. However, surgical management is required in most cases in which
      radiological intervention is unsuccessful. In this report, we describe a case of
      a 67-year-old woman with recurrent bilioenteric anastomotic stricture,
      accompanying bilateral hepatolitiasis after several times of transhepatic
      interventions. The patient underwent intrahepatic cholangiojejunostomy (Longmire
      procedure) and cholangioscopic lithotomy after resection of an atrophic left
      lateral segment resulting from hepatolithiasis. Although the damaged hilar bile
      duct had to be isolated and divided from the corresponding vasculature for re
      anastomosis, it was quite impossible due to severe inflammatory change at the
      hepatic hilus. We, therefore, anastomosed the intact biliary stump on the cut
      surface of the left lateral segment to the jejunal loop with a stent tube. The
      patient's postoperative course was uneventful and she exhibited no evidence of
      cholangitis during follow-up period of 1 year after surgery. At present, the
      indications for intrahepatic cholangiojejunostomy for biliary obstruction, are
      quite limited, but biliary surgeons should keep this procedure in mind at the
      time of biliary reconstruction for benign proximal bile duct stricture,
      particularly in cases of multiply operated hilum.

PMID- 22580653
TI  - Thrombocytosis following splenectomy: with or without additional organ resection.
AB  - BACKGROUND/AIMS: Splenectomy is one of the main causes of reactive
      thrombocytosis. In most cases, thrombocytosis found incidentally is harmless and
      resolves spontaneously; however, extreme thrombocytosis may result in thrombotic
      events such as acute myocardial infarction, mesenteric vein thrombosis and
      pulmonary embolism. Thus, there are no clear indications for determining which
      patients with reactive thrombocytosis require treatment. In this study, we
      evaluated reactive thrombocytosis that developed after splenectomy with or
      without additional organ resection. METHODOLOGY: We retrospectively studied 70
      patients who underwent splenectomy. These patients were divided into 2 groups:
      the only splenectomy group (group A) and the splenectomy with additional organ
      resection group (group B). RESULTS: Both the platelet count at 1 week and 1 month
      after the operation (p<0.01 and p<0.001, respectively) and the incidence rate of
      thrombocytosis at 1 week and 1 month (p<0.4089 and p<0.0007, respectively) were
      significantly higher in group A than in group B. All patients in both groups
      recovered from thrombocytosis without any platelet reduction therapy and there
      was no postoperative thrombosis. CONCLUSIONS: Splenectomy often results in
      reactive thrombocytosis; however, platelet reduction therapy is not required for
      treating postsplenectomy reactive thrombocytosis.

PMID- 22580654
TI  - Terlipressin in the treatment of late phase catecholamine-resistant septic shock.
AB  - BACKGROUND/AIMS: Norepinephrine, but also dopamine and epinephrine are
      recommended as first line vasopressors in the treatment of septic shock. In some
      patients, septic shock deteriorates and becomes to be resistant to
      catecholamines. In this situation, addition of vasopressin or terlipressin can be
      advantageous. The aim of our pilot study was to evaluate the impact of
      terlipressin on open label norepinephrine requirements and mortality.
      METHODOLOGY: In a randomized, controlled, single centre study we assigned
      patients with late advanced septic shock refractory to catecholamines
      (norepinephrine >0.6ug/kg/min for more than 24h) to receive either continuously
      terlipressin 4mg/24h for 72 hours in addition to open label norepinephrine (TERLI
      group) or to continue therapy only with catecholamines (CON group). All
      vasopressor infusions were titrated to maintain a target blood pressure. RESULTS:
      We enrolled 30 patients, of whom 13 were assigned to terlipressin and in 17 we
      continued in catecholamine therapy. There was no significant difference in
      norepinephrine consumption between the groups. Open label norepinephrine infusion
      rates decreased significantly in the TERLI group as compared with initial
      consumption, but the decrease we observed only in 7 (54%) patients. There was no
      significant difference between groups in the rate of death at day 28 (77% in
      TERLI group and 94% in CON group; p=0.18) or at day 90 (91% vs. 94%; p=0.85).
      CONCLUSIONS: Continuous terlipressin infusion was not effective in reducing
      norepinephrine consumption or in the mortality of patients, if administered in
      late phase of catecholamine refractory septic shock.

PMID- 22580655
TI  - Thymidylate synthase (TS) protein expression as a prognostic factor in advanced
      colorectal cancer: a comparison with TS mRNA expression.
AB  - BACKGROUND/AIMS: The role of intratumoral thymidylate synthase (TS) mRNA or
      protein expression is still controversial and little has been reported regarding
      relation of them in colorectal cancer. METHODOLOGY: Forty-six patients with
      advanced colorectal cancer who underwent surgical resection were included. TS
      mRNA expression was determined by the Danenberg tumor profile method based on
      laser-captured micro-dissection of the tumor cells. TS protein expression was
      evaluated using immunohistochemical staining. RESULTS: TS mRNA expression tended
      to relate TS protein expression. Statistical significance was not found in
      overall survival between the TS mRNA high group and low group regardless of
      performing adjuvant chemotherapy. The overall survival in the TS protein negative
      group was significantly higher than that in positive group in all and the
      patients without adjuvant chemotherapy. Multivariate analysis showed TS protein
      expression was as an independent prognostic factor. CONCLUSIONS: TS protein
      expression tends to be related TS mRNA expression and is an independent
      prognostic factor in advanced colorectal cancer.

PMID- 22580656
TI  - Surgical technique for the transperineal approach of anterior levatorplasty and
      recto-vaginal septum reinforcement in rectocele patients with soiling and
      postoperative clinical outcomes.
AB  - BACKGROUND/AIMS: To clarify the significance of a transperineal approach of
      anterior levatorplasty (ALP) and recto-vaginal septum reinforcement in rectocele
      patients with soiling, we reported the surgical technique and clinical outcomes
      two years after this operation. METHODOLOGY: Twelve female patients (33-82 years,
      average 63.3) complaining of defecation disorders (disturbed defecation including
      excessive straining during defecation, sensation of incomplete defecation and
      manual assistance of digitation of the vagina) with soiling underwent the
      following surgical technique: under spinal anesthesia, rectal wall was opened up
      to the end of the rectal wall weakness. Rectocele in the weak rectal wall was
      horizontally sutured. Before closing wound ALP was fashioned. RESULTS: In
      clinical outcomes, excessive straining during defecation, sensation of incomplete
      evacuation and defecation by manual assistance were statistically significantly
      reduced postoperatively after a follow-up of 2 years (p<0.01, p<0.01, p<0.0001,
      p<0.01, respectively). As an early postoperative complication, perineal wound
      infection was noted in one patient. Late postoperative complications were not
      noted in any patient. In overall patient satisfaction 2 years after operation,
      half of the patients were excellent and no patients were poor. CONCLUSIONS:
      Combined repair of rectocele and ALP by transperineal approach may be a useful
      procedure for correcting rectocele with soiling. This procedure is also easy and
      safe.

PMID- 22580657
TI  - Can immunohistochemistry of multidrug-resistant proteins replace the histoculture
      drug response assay in colorectal adenocarcinomas?
AB  - BACKGROUND/AIMS: To investigate 1) whether immunohistochemistry of multidrug
      resistant (MDR) proteins (MDR1, MRP1, MRP2 and BCRP) in colorectal
      adenocarcinomas can substitute for histoculture drug response assays (HDRA) and
      2) whether chemosensitivity as indicated by HDRA and MDR protein expression is
      related to prognostic parameters in colorectal cancers. METHODOLOGY:
      Chemosensitivity of cancer tissues to 5-FU, irinotecan and oxaliplatin was
      assessed by HDRA. Immunohistochemical staining of MDR proteins was quantified by
      image analysis in 76 colorectal adenocarcinoma patients. RESULTS: Inhibition
      rates (IRs) of the anticancer drugs by HDRA were not related to MDR protein
      expression. However, the IR of 5-FU was significantly decreased with lymph node
      metastasis (p=0.03) and advanced clinical stages (p=0.047). The IRs of irinotecan
      and oxaliplatin were not associated with clinicopathological parameters.
      Immunohistochemically, positive scores for MRP2 and BCRP protein were
      paradoxically related to lower clinical stages (p=0.043) and male gender
      (p=0.019), respectively. CONCLUSIONS: Immunohistochemical staining of MDR
      proteins can not predict tumor responses to anticancer drugs in colorectal
      cancers. Chemoresistance to 5-FU as indicated by HDRA was highly associated with
      aggressive prognostic factors.

PMID- 22580659
TI  - Time trend and risk factors for reoperation in Crohn's disease in Japan.
AB  - BACKGROUND/AIMS: We aimed to evaluate time changes in reoperation rate after
      initial surgery in Crohn's disease (CD) over the last five decades in Japan and
      to assess the risk factors for reoperation, given that a decrease in the
      reoperation rate for CD remains controversial. METHODOLOGY: CD patients (n-476)
      who underwent initial intestinal surgery were examined. Case records were
      collected from 13 institutions and scrutinized retrospectively. The primary
      outcome measure was the reoperation rate needing intestinal surgery. To evaluate
      the time changes, we compared medical treatment and reoperation rate in patients
      from two different periods of time; before and after 2002 when infliximab became
      available in Japan (1963-2002 and 2003-2008 groups). Univariate and multivariate
      analyses were performed to examine the influence of independent variables on the
      cumulative reoperation rate. RESULTS: A total of 201 patients underwent
      reoperation. Overall 5-year and 10-year cumulative reoperation rates were 31.4%
      and 61.2%, respectively. In multivariate analysis, an onset of the disease
      between 1963-2002 (p=0.0199) and postoperative administration of infliximab
      (p=0.0003) and immunosuppressants (p<0.0001) were significant risk factors for
      reoperation. The cumulative 5-year reoperation rate decreased significantly in
      the 2003-2008 group compared to the 1963-2002 group (6.3% vs. 32.9%, p<0.05).
      CONCLUSIONS: The reoperation rate for CD has decreased significantly in recent
      years in Japan. However, to further confirm this time trend, we need to evaluate
      CD patients with a longer follow-up period.

PMID- 22580658
TI  - Central venous port system-related complications in outpatient chemotherapy for
      colorectal cancer.
AB  - BACKGROUND/AIMS: The current standard chemotherapy for metastatic colorectal
      cancer is the FOLFOX or the FOLFIRI regimen. Although these regimens include the
      continuous infusion of an anticancer agent, chemotherapy is possible by using
      implantable central venous port systems with a portable disposable pump in an
      outpatient setting. This study is an evaluation of the usefulness of implantable
      central venous port systems for colorectal cancer chemotherapy. METHODOLOGY: An
      implantable central venous port system was placed in 93 consecutive patients with
      metastatic colorectal cancer. All patients received modified FOLFOX6 +/-
      bevacizumab or FOLFIRI +/- bevacizumab regimens via the port system. Follow-up
      continued for each patient until removal of the port system, death or
      unavailability of further information. The incidence and details of the
      complications were investigated retrospectively. RESULTS: Out of 1,246
      treatments, a total of 16 incidents of port system-related complications were
      identified (1.28%). Incidents involved infections (n=12), catheter pinch off
      (n=2), fibrin sheath (n=1) and drug leakage (n=1). A port system removal was
      required in 14 cases. CONCLUSIONS: Implantable central venous port systems are
      safe and have a low long-term complication rate. We consider port systems, such
      as modified FOLFOX6 +/- bevacizumab or FOLFIRI +/- bevacizumab regimens, useful
      for colorectal cancer patients receiving chemotherapy.

PMID- 22580660
TI  - Cytomegalovirus infection in patients with new onset ulcerative colitis: a
      prospective study.
AB  - BACKGROUND/AIMS: Immunosuppressive therapy in ulcerative colitis (UC) may induce
      cytomegalovirus (CMV) infection or reactivation in the colonic mucosa and in turn
      exacerbate UC. However, it is unclear whether colonic inflammation itself affects
      CMV infection in UC. This prospective study evaluated the prevalence and clinical
      outcome of CMV infection in patients with new onset UC who have not been exposed
      to UC medication. METHODOLOGY: A prospective, multi-center study was conducted in
      65 patients with new onset UC. The presence of CMV was evaluated by a serology
      test and a histopathological examination including immunohistochemical staining.
      The assessment of clinical outcome was performed based on CMV positivity.
      RESULTS: Evidence of CMV infection was found in three (4.5%) patients with UC.
      Two patients with moderate disease activity improved with 5-aminosalicylate or
      steroid treatment. One patient with severe active colitis, however, required
      antiviral therapy. CONCLUSIONS: CMV infection is rare in new onset UC, which
      suggests that use of immunosuppressive medications is an important risk factor
      for CMV infection in UC. However, CMV evaluation is necessary for severe active
      UC, even with new onset of the disease.

PMID- 22580661
TI  - Anti-angiogenic therapy for colorectal cancer: on the way to getting better!
AB  - Based on the theory that tumor growth and metastasis depend on vessels to provide
      oxygen and nutrients, antiangiogenic therapy was thought as a promising approach
      to cure cancer. Bevacizumab is the first validated angiogenesis inhibitor, when
      combined with conventional treatments, which can enhance antitumor effects and
      prolong survival for patients with colorectal cancer. However, recent years,
      bevacizumab and other angiogenesis inhibitors are more discussed with drug
      resistance and the diverse test results. Fortunately, antiangiogenic strategy is
      more than bevacizumab and more than anti-vascular endothelial growth factor.
      Dozens of compounds that potently inhibit neoplastic blood vessels formation with
      different mechanisms have been developed, and many of them are being tested
      clinically for colorectal cancer. This review will numerate the principal
      antiangiogenic drugs with various mechanisms, recapitulate the information of
      studying these drugs for colorectal cancer treatment and try to clue better usage
      of antiangiogenic therapy for patients with colorectal cancer in the future.

PMID- 22580662
TI  - Patients with partial gastrectomy and Barrett esophagus are in higher risk to
      develop esophageal adenocarcinoma than those with Barretts without gastrectomy.
AB  - BACKGROUND/AIMS: Duodenogastric reflux is a possible risk factor for esophageal
      adenocarcinoma (CA) development. Gastric surgery that destroys or distorts the
      pylorus is a good model to study the effects of duodenogastric reflux. To define
      the consequences of gastrectomy in patients with Barrett esophagus (BE).
      METHODOLOGY: Records of all BE/CA patients examined in Blackpool-Wyre-Fylde area
      were reviewed. All surviving patients completed validated questionnaires.
      RESULTS: Gastrectomy was more prevalent in CA patients (14 (3.6%) BE vs. 15
      (13.3%) CA, p=0.0002). Partial gastrectomy was more prevalent in CA patients, (7
      (1.8%) BE vs. 10 (8.8%) CA, p=0.0004), while there was no difference in total
      gastrectomy between the two groups. Persistence of H. pylori infection after
      gastrectomy and smoking were more frequent among CA patients with gastrectomy.
      Mean follow-up time in patients with prior gastrectomy was 78 (SD=76.4) months
      for BE patients and 119.3 (SD=72.9) months for CA patients (p=0.07). In logistic
      regression analysis gastrectomy, in addition to old age, long-term reflux,
      absence of hiatal hernia and H. pylori infection were risk factors for CA.
      CONCLUSIONS: Gastrectomy and especially partial gastrectomy was more prevalent in
      CA patients.

PMID- 22580663
TI  - Heterotopic gastric mucosa in the upper and middle esophagus: 126 cases of
      gastroscope and clinical characteristics.
AB  - BACKGROUND/AIMS: In this retrospective study, we aimed to investigate the
      prevalence of heterotopic gastric mucosa (HGM) in the upper and middle esophagus,
      to identify its macroscopic characteristics and evaluate clinical features.
      METHODOLOGY: One hundred and twenty-six patients (82 males, 44 females; mean age
      43.08 +/- 12.84 years, range 15-81) with HGM in the upper and middle esophagus
      diagnosed by gastroscopy and biopsies were admitted to this retrospective study.
      Disease histories of all patients were carefully inquired, especially the
      associated complaints including discomfort of throat, heartburn or dysphagia,
      etc. RESULTS: The prevalence was 0.21%. Patch size ranged between 5-20mm, mean
      diameter was 7.5 +/- 3.7mm; 80 cases appeared as a single patch; 96.83% had the
      patch in the upper esophagus. Male gender was predominant (male:female ratio,
      1.86), but age was not significant. The mean distance from the incisors to the
      patch was 18.83 +/- 2.23cm and 17.20 +/- 2.48cm in the male and the female
      respectively, with a significant difference (t=3.749, p<0.001). In 39 of 126
      patients (26 male, 13 female), the esophageal and laryngopharyngeal symptoms were
      remarkable. Twelve were associated with other diseases of the esophagus. There
      were no correlations to esophageal symptom, gender, age, location, quantity or
      diameter. Among the 126 cases, 29 patients were associated with other esophageal
      diseases. CONCLUSIONS: HGM patches in the esophagus should not be overlooked
      during endoscopy because they may lead to esophageal symptoms and even important
      complications in relation to their acid secretions.

PMID- 22580664
TI  - Natural orifice transluminal endoscopic surgery in surgical oncology: analysis of
      indications and feasibility in cancer patients.
AB  - BACKGROUND/AIMS: Natural orifice endoscopic surgery (NOTES) is an emerging
      technique that has been postulated as a promising alternative to laparoscopy in
      the field of minimal invasive surgery. Until now appropriate indications, safe
      access routes and general feasibility of this approach have not been defined
      exactly in surgical oncology. METHODOLOGY: A total of 474 patients undergoing
      cancer surgery were analyzed regarding possible applications of transluminal
      endoscopic surgery. Patient with potential indications underwent intraoperative
      endoscopy to evaluate technical aspects, indications and intraoperative
      feasibility. RESULTS: A potential indication for transluminal surgery was found
      in 54 of 474 patients (11%) undergoing abdominal cancer surgery. Staging of
      gastrointestinal tumors was considered the main indication (45%) followed by
      splenectomy (11%) and diagnostic excision (11%). As a potential access route the
      transgastric approach was considered in 42 patients (66%) and the transcolonic
      approach in 18 patients (28 %). Of these 42 patients, 19 (30%) presented with
      significant intra-abdominal adhesions which would have resulted in a more
      complicated procedure. Accurate transluminal orientation was considered
      impossible in 13 cases (20%). CONCLUSIONS: Although some indications for NOTES
      procedures in surgical oncology have been identified in this study these
      techniques have to be assessed cautiously. Implementation of NOTES in surgical
      oncology is currently difficult because of technical problems, lack of
      intraoperative orientation and abdominal adhesions.

PMID- 22580665
TI  - Early results of laparoscopic resection of the stomach.
AB  - BACKGROUND/AIMS: In this study we present our experiences and results in patients
      who underwent laparoscopic resection of the stomach. METHODOLOGY: Our study
      presents five patients that underwent laparoscopy in the period 2006-2008, at the
      surgical department of the General hospital Djordje Joanovic in Zrenjanin,
      Serbia. Four of them were verified with stomach cancer and one with benign
      stenosis of the pylorus region. All patients underwent identical preoperational
      preparation. The most sophisticated laparoscopic equipment was used. All patients
      were monitored pre- and postoperatively. RESULTS: Laparoscopic resection of the
      stomach was performed in 5 patients (3 men and 2 women), 39 to 66 yrs old (mean:
      55 years); in four patients using the Billroth II procedure and in one patient as
      total gastrectomy with splenectomy in accordance to oncological principles. In
      four patients there was a malignant lesion of the stomach in the antral region
      and in one patient benign pyloric stenosis. Intraoperational complications
      occurred in two patients. Intraoperational bleeding of 350mL occurred in one
      patient, and in one patient there was jamming the stapler head in the esophagus
      during the creation of esophagojejunal anastomosis. Postoperatively, fistula
      anastomosis occurred in one patient and vomiting occurred in another. One patient
      died 11 months after the operation while 4 patients are still being monitored.
      CONCLUSIONS: Early results are satisfying. Laparoscopic gastrectomy has
      indisputable advantages for treatment of benign stomach diseases. Technical
      equipment and good operational techniques enables radicality of operational
      procedures in malignant diseases.

PMID- 22580666
TI  - Standardized laparoscopy-assisted distal gastrectomy with a novel surgical
      technique for lifting the liver.
AB  - BACKGROUND/AIMS: It is very important to achieve a sufficient field and space in
      laparoscopic assisted distal gastrectomy (LADG) for a less-experienced surgeon.
      In this study, the usefulness of a novel surgical technique to lift the liver was
      evaluated in LADG. METHODOLOGY: Fifty-four patients who underwent standardized
      LADG for gastric cancer using the novel technique of lifting the liver were
      retrospectively evaluated based on video records. Patient characteristics, the
      time required to lift the liver and for gastrectomy, total operation time, blood
      loss and complications were analyzed. RESULTS: The mean time necessary to lift
      the liver using this novel technique was 240.1+/-86.1 seconds and that for
      gastrectomy was 167.6+/-50.4 minutes. Blood loss was 72.5+/-59.6mL. The morbidity
      rate was 4/54 (7.4%). CONCLUSIONS: Standardized LADG using this novel technique
      is feasible and possible in a period of time.

PMID- 22580667
TI  - Comparison of postoperative morbidity in elderly patients who underwent
      pancreatic resection.
AB  - BACKGROUND/AIMS: Operative indications for pancreatectomy in elderly patients
      with pancreatic disease remain controversial. We examined clinicopathological
      characteristics and early outcomes in each generation of 147 patients who
      underwent pancreatectomy. METHODOLOGY: Patients were divided into four groups:
      Group 1 (n=15, 10%), young patients <50 years old; Group 2 (n=65; 44%), patients
      at 50- 69 years old; Group 3 (n=61, 42%), patients at 70-79 years old and Group 4
      (n=6, 4%), elderly patients >80 years old. Clinicopathological and surgical
      parameters were examined, including estimation of physiological ability and
      surgical stress consisting of preoperative risk score (PRS), surgical stress
      score (SSS) and comprehensive risk score (CRS). RESULTS: Prevalence of co
      morbidity and American Society of Anesthesiologists (ASA) score increased
      significantly with increasing patient age (p<0.05). Extent of pancreatectomy and
      lymphadenectomy did not differ between groups and surgical records were similar.
      Tumor stage, postoperative course and complications were similar between groups.
      PRS and CRS increased significantly with increasing patient age (p<0.05) but SSS
      did not. Univariate analysis identified presence of systemic comorbidity, ASA
      score =2 and PRS =0.32 as factors associated with postoperative complications,
      but no independent predictive parameters were identified on multivariate
      analysis. CONCLUSIONS: Careful management and adequate decisions regarding
      pancreatectomy upon identification of co-morbidity, ASA score and PRS are
      important in elderly patients with pancreatic disease before pancreatectomy.

PMID- 22580668
TI  - Endoscopic and pathological aspects of gastric polyps: a Turkish referral center
      study.
AB  - BACKGROUND/AIMS: The aim of the present study was to retrospectively analyze all
      the polyps of patients undergoing endoscopic polypectomy or forceps biopsy
      according to their types, frequency, localization, number and gender
      distribution. METHODOLOGY: Data from patients who underwent upper endoscopy in
      the Turkiye Yuksek Ihtisas Postgraduate Research Hospital between March 2007 and
      November 2009 were analyzed retrospectively. Forceps biopsy or polypectomy were
      performed for all polypoid lesions that were identified during the endoscopy.
      RESULTS: In the study period, 14,935 patients underwent 18,522 upper endoscopies.
      After excluding cirrhotic patients, and patients with a history of prior
      gastrectomy, chronic gastritis and edema or congestion, the remaining 124 (0.83%)
      patients with gastric polyps were included in the study. Histopathologically, the
      most frequently diagnosed polyps were hyperplastic polyps (55.6%). Fundic gland
      polyps (9.7%), foveolar hyperplasia (8.1%) and inflammatory polyps (7.3%) were
      also frequent. Adenocarcinoma was more frequently seen in males, whereas
      hyperplastic polyps and carcinoid tumors were found more often in females, and
      this difference was statistically significant (p<0.009). CONCLUSIONS: Results of
      the present study indicate that hyperplastic polyps make up the largest group.
      Although there is widespread PPI use, no increases in the frequency of fundic
      gland polyps were observed. However, increases in the ratio of carcinoid tumors
      suggest a suspicion of tumor development with PPI use.

PMID- 22580669
TI  - Combined splenectomy does not improve survival in radical total gastrectomy for
      advanced gastric cardia cancer.
AB  - BACKGROUND/AIMS: Splenectomy is the most common combined organ resection in the
      surgical management for gastric cardia cancer. The role of combined splenectomy
      is still controversial. METHODOLOGY: From January 1998 to December 2006, a total
      of 174 patients received radical total gastrectomy for advanced adenocarcinoma of
      cardia. Patients with previous gastric surgery or tumor invasion of pancreas or
      spleen were excluded. Among them, 115 patients were enrolled in this study.
      Patients were divided into group 1 (splenectomy, n=47) and group 2 (spleen
      preservation, n=68). Their clinicopathological characteristics were compared.
      RESULTS: Multivariate analysis showed that only tumor size and lymphovascular
      invasion were two independent indicators of survival. The surgically-related
      morbidity and mortality rates were similar between the two groups. Among the 3
      patients with splenic hilar lymph nodes metastasis, all of them had large tumor
      size (=4cm), advanced stage (stage III and IV) and tumor center located at the
      posterior wall of stomach. The 5-year overall survival for advanced cancer was
      similar (57.1% vs. 60.2%, p=0.681). CONCLUSIONS: Splenectomy does not improve
      overall survival in the management of advanced gastric cardia cancer. Splenectomy
      has limited clinical benefits except for large advanced tumors located at the
      posterior wall of stomach.

PMID- 22580670
TI  - Primary vs. secondary anastomosis for superior mesenteric arterial occlusion.
AB  - BACKGROUND/AIMS: Superior mesenteric arterial occlusion (SMAO) often requires
      massive bowel resection. We compared primary anastomosis with open abdominal
      surgery and secondary anastomosis after enterostomy creation for the management
      of SMAO. METHODOLOGY: We retrospectively studied 27 patients who underwent
      massive bowel resection for SMAO; the patients were divided into 2 groups
      depending on the operative procedure: primary anastomosis with open abdominal
      surgery (P group) and secondary anastomosis after enterostomy creation (S group).
      RESULTS: The mean duration from the initial operation to final operation (closure
      of open abdomen or closure of enterostomy) was significantly shorter in the P
      group (4.6+/-0.9 days) than in the S group (26.8+/-9.4 days) (p<0.0001). No
      disease recurrence was observed in either group; however, 2 patients died of
      multiple organ failure in the S group. CONCLUSIONS: Primary anastomosis with open
      abdominal surgery is useful for patients with low acute physiology and chronic
      health evaluation (APACHE) II scores and secondary anastomosis should be
      performed in patients with high APACHE II scores. Further, it is important to
      perform timely enterostomy closure on the basis of precise examination of blood
      flow in the remnant bowel to avoid deterioration in the patients' quality of
      life.

PMID- 22580671
TI  - Study of perioperative liver function by dynamic monitoring of ICG-clearance.
AB  - BACKGROUND/AIMS: To investigate the impact of liver resection on the
      perioperative hepatic function by evaluation of ICG-clearance. METHODOLOGY:
      Twenty-five patients underwent major hepatic resection (Group A) and 36 underwent
      minor hepatic resection (Group B). Thirteen patients who received no liver
      surgery, acted as control group (Group C). ICG-clearance measured by a non
      invasive technique was expressed in terms of plasma disappearance rate (PDR-ICG
      %/min) and retention rate of ICG 15 min (ICG-R15-%) after administration ICG
      (0.5mg/kg) before anesthesia induction (T0), immediately after the surgery (T1)
      and 24h after (T2). RESULTS: There was statistically significant differences
      between the three groups: ICG-PDR (p<0.004) and ICG-R15 (p<0.040). These
      differences were observed between groups A and C at T1, between A and B, or A and
      C, at T2 for ICG-PDR and between groups A and B at T2 for ICG-R15. There were no
      differences between groups for hemoglobin, platelets, PT, creatinine, albumin,
      total protein, bilirubin and ALP. CONCLUSIONS: ICG clearance is a safe non
      invasive dynamic tool to quantify the liver function in patients following
      hepatic surgery. It also can be used to evaluate the liver surgery impact on
      hepatic function which can help to diagnose early hepatic dysfunction and guide
      the therapeutic decision making process.

PMID- 22580672
TI  - Intensive pulmonary support using extracorporeal membrane oxygenation in adult
      patients undergoing liver transplantation.
AB  - BACKGROUND/AIMS: Adult liver transplantation (LT) recipients occasionally show
      serious acute cardiopulmonary dysfunction, requiring intensive care. We have
      assessed the feasibility of extracorporeal membrane oxygenation (ECMO) support in
      adult LT recipients facing acute pulmonary failure and refractory to conventional
      mechanical ventilation and concurrent nitric oxide gas inhalation. METHODOLOGY:
      From January 2008 to June 2009, 9 adult LT recipients required ECMO support due
      to pneumonia (n=5) and adult respiratory distress syndrome (n=4). Mean age was
      52.6 +/- 5.9 years and mean model for end-stage liver disease score was 29.0 +/-
      7.5. Five patients underwent living-donor LT and four underwent deceased-donor
      LT. RESULTS: Veno-venous access mode was used and continuous veno-venous
      hemodiafiltration was performed concurrently in all 9 patients. No procedure
      related complications occurred. Successful ECMO weaning was achieved in 4
      patients (44.4%) at the first attempt, after mean ECMO support of 12.0 +/- 6.8
      days but the other five died due to overwhelming infection prior to ECMO weaning.
      Univariate analysis revealed no significant risk factors for failing ECMO support
      before ECMO start. CONCLUSIONS: ECMO as rescue therapy seems beneficial to be
      considered as a final therapeutic option for LT recipients with refractory
      pulmonary dysfunction who would otherwise die due to hypoxemia.

PMID- 22580673
TI  - Adjuvant transarterial chemoembolization after curative resection of
      hepatocellular carcinoma: a non-randomized comparative study.
AB  - BACKGROUND/AIMS: Prevention of recurrence is the most important strategy to
      improve long-term survival after resection of hepatocellular carcinoma (HCC).
      This comparative study aimed to evaluate the outcome of adjuvant transarterial
      chemoembolization (TACE) after hepatectomy. METHODOLOGY: From February 1996 and
      September 2001, 721 consecutive patients (adjuvant TACE treatment vs. control
      group; 145 vs. 576) with R0 resection for HCC were analyzed. The prospective data
      was analyzed retrospectively. RESULTS: After a median follow-up of 75 months, 89
      patients (61.4%) in the adjuvant TACE group and 355 patients (61.6%) in the
      control group had recurrent disease. There was no significant difference in the
      tumor recurrence rate between the 2 groups. There was significant difference in
      the tumor recurrence time between the 2 groups. The 1-, 3- and 5-year overall
      survival rates were 96.5%, 70.0% and 55.9%, respectively, for the adjuvant TACE
      group and 80.8%, 49.7% and 38.8%, respectively, for the control group. The 1-, 3-
      and 5-year disease-free survival rates were 79.9%, 54.9% and 48.4%, respectively,
      for the adjuvant TACE group and 60.2%, 39.8% and 31.5%, respectively, for the
      control group. The differences in the disease-free survival rates and the overall
      survival rates between the 2 groups were significant. In subgroup analysis, there
      was significant survival benefit in the adjuvant TACE group in the subgroup of
      patients with risk factors of recurrence - large tumor size, presence of
      satellite tumor nodules and narrow resection margin. CONCLUSIONS: Adjuvant TACE
      improved surgical outcome in those patients with risk factors of HCC recurrence.

PMID- 22580674
TI  - Amount of operative blood loss affects the long-term outcome after liver
      resection for hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Numerous prognostic factors for HCC have been reported. Few
      literatures have reported clinical significance of amount of intraoperative blood
      loss (ABL) for the outcome after surgery for HCC. The aim of this study is to
      analyze the significance of ABL for outcome after surgery for HCC. METHODOLOGY: A
      total of 301 patients who underwent liver resection for HCC between January 1998
      and June 2007 were included. Clinical and surgical characteristics were collected
      and prognostic factors were identified using univariate and multivariate
      analysis. RESULTS: Impaired liver function (liver damage B), large tumor (>36mm),
      multiple tumors, existence of macroscopic vessel invasion, large ABL (=700mL) and
      replacement of red blood cells were identified as independent prognostic factors
      for overall survival (OS). For disease free survival (DFS), old age (>66), male
      gender, impaired liver function, large tumor, multiple tumors, existence of
      macroscopic vessel invasion and large ABL were extracted. Limited to the patients
      without blood transfusion, large ABL is associated with poor OS and DFS.
      CONCLUSIONS: Large ABL could result in poor OS and DFS after liver resection of
      HCC in patients without blood transfusion. Surgeons have to make the best effort
      to reduce ABL.

PMID- 22580675
TI  - Evaluation of mass-forming intrahepatic cholangiocarcinoma with viral hepatitis.
AB  - BACKGROUND/AIMS: The correlation between the mass-forming type of intrahepatic
      cholangiocarcinoma (ICC) and the infection of the hepatitis B virus and hepatitis
      C virus are poorly understood. In this study, the clinical features of 34
      patients with the mass-forming type ICC were reviewed to evaluate prognostic
      determinants. METHODOLOGY: Between January 1997 and December 2007, 34 patients
      underwent surgical resection for the mass-forming type of ICC in Kumamoto
      University Hospital. The significance of 14 clinicopathological factors
      consisting of age, gender, CA19-9 levels, CEA levels, size, intrahepatic
      metastases, portal vein invasion, bile duct invasion, histological
      differentiation, lymph node involvement, type B or C hepatitis, lymph node
      dissection, Sirius Red score of the tumor and platelet count in peripheral blood
      were analyzed, with regard to prognostic aspect. RESULTS: Univariate analysis
      showed that significant risk factors for poor survival included age =65 years,
      CEA levels =1.6ng/mL and pathological lymph node involvement. Multivariate
      analysis revealed that age, CEA levels and lymph node involvement were
      independent and significant poor prognostic factors. CONCLUSIONS: It was
      concluded that age, CEA levels and lymph node involvement were significantly poor
      prognostic factors. However, the infection with type B or C hepatitis was not a
      prognostic factor of the mass forming type ICC.

PMID- 22580676
TI  - Role of autophagy in monokine induced by interferon gamma (Mig) production during
      adenovirus-hepatitis B virus infection.
AB  - BACKGROUND/AIMS: The aim of this study was to investigate the effect of HBV
      induced Mig and role of autophagy in the process. METHODOLOGY: Adxsi-1.3 x HBV
      plasmid was constructed and identified. The three cell lines (L02, HepG2, SMMC
      7721) were infected with adenovirus-HBV. HBsAg and HBeAg were assessed by
      electrochemiluminescence immunoassay. HBV DNA, HBx, Beclin 1 and Mig expression
      were detected by quantitative real-Time PCR, western blotting and ELISA. The
      level of autophagy was evaluated by transmission electron microscope. RESULTS:
      Human fetal liver cells and hepatocellular carcinoma cells were successfully
      transfected with overlength HBV genome using an adenovirus vector (Ad-HBV). Ad
      HBV induced Mig production and cell autophagy through up-regulation of Beclin 1
      expression. We further demonstrated that the increased autophagy extent was in
      association with HBV-induced Mig expression. CONCLUSIONS: Autophagy may be a
      crucial intracellular mechanism of Mig induction in response to HBV infection.
      The results provide new insights into the pathogenesis of HBV.

PMID- 22580677
TI  - Exacerbation of chronic hepatitis B during chemotherapy due to testicular
      seminoma.
AB  - Chronic hepatitis B is often asymptomatic until it progresses to advanced stage.
      The natural course of disease includes flares and periods of decreased
      inflammatory activity. Immune decline status is proven risk factor for
      exacerbation of viral hepatitis. Anticancer chemotherapy in chronic HBsAg
      carriers is known to promote viral replication. Return of immunocompetence after
      withdrawal of immunosuppressant might result in liver damage. We describe case of
      a patient with chronic HBV infection who developed hepatitis flare subsequently
      to the cessation of anti-viral treatment and introduction of chemotherapy due to
      testicular seminoma. Patients with history of HBV infection who receive
      immunosuppressive treatment are at risk of HBV reactivation or exacerbation of
      hepatitis. During immunosuppressive treatment enhanced HBV replication and
      inhibition of CTL without evident liver injury is observed. Restoration of immune
      system after withdrawal of immunosuppressant allows recognizing increased
      expression of HBV antigens in hepatocytes. Intensive elimination of infected
      hepatocytes could occur resulting in liver tissue necrosis, active hepatitis and
      liver decompensation. It is recommended for HBV infected patients on
      immunosuppressive treatment to receive antiviral therapy, particularly with the
      lowest risk for the selection of mutations, regardless the stage of infection.

PMID- 22580678
TI  - Ciliated hepatic foregut cyst: two further cases with an immunohistochemical
      analysis.
AB  - The objective of the present study is to report two cases of a rare entity, which
      is being increasingly recognized in recent years. A 35-year-old woman and a 33
      year old man were incidentally discovered to have bilocular cystic hepatic masses
      affecting segment IV. In both cases the cystic mass was excised and the
      histopathological analysis revealed an inner lining of the cyst wall with a
      pseudostratified epithelium showing prominent cilia. The cyst wall contained some
      muscular fibers but no cartilage or other tissue types and diagnosis was ciliated
      hepatic cyst. Both patients recovered uneventfully after surgery and are well and
      disease free. Ciliated hepatic cysts are rare cystic hepatic masses derived from
      remnants of the embryonal foregut that are embedded inside the hepatic bud during
      embryological development. Fewer than 100 cases of this tumor have been reported
      in the world literature, many of them in Japan, and most cases have behaved in a
      benign fashion, although there are at least three reported cases of malignancy
      within the cyst wall to a squamous cell carcinoma. We herein report two further
      cases of this entity, highlight the diagnostic usefulness of immunohistochemistry
      and comment on the possible therapeutic alternatives.

PMID- 22580679
TI  - Surgical treatment of pain in patients with chronic pancreatitis.
AB  - BACKGROUND/AIMS: The objectives of the research were to compare the outcomes of
      pancreatoduodenectomy (PD) (Kausch-Whipple or Traverso-Longmire) and resection
      with drainage operations (RDO) (Frey or Partingtone-Rochelle) in patients
      suffering from chronic pancreatitis (CP), in management of pain syndrome and
      quality of life provided by these kinds of surgical procedures. METHODOLOGY: From
      2002 to 2008 sixteen patients suffering from CP underwent PD and 16 underwent
      RDO. Treatment results for the two groups were analyzed with respect to
      postoperative complications and results of the questionnaire MOS SF-36 v.2(TM).
      RESULTS: In the immediate postoperative period more complications were observed
      in the PD group (a<0.05). In both groups a positive effect on removing the
      painful syndrome and improvement of the quality of life (p<0.01) were observed.
      In the PD group there were the best results of management by General Health
      difference criterion (a<0.01). A greater improvement of Physical Functiong value
      (a<0.01) was noticed in patients who underwent RDO. CONCLUSIONS: Both PD and RDO
      adequately remove pain syndrome and improve the quality of life in patients
      suffering from CP. Under equal conditions the preference should be given to RDO,
      as improvement in life quality of operated patients is greater.

PMID- 22580680
TI  - Antecolic and retrocolic route on delayed gastric emptying after MSSPPD.
AB  - BACKGROUND/AIMS: Previously, we developed a modified subtotal stomach-preserving
      pancreaticoduodenectomy for preventing delayed gastric emptying and achieved a
      decrease in the incidence of delayed gastric emptying. In this study, we compared
      the antecolic and retrocolic routes to determine which reconstruction route is
      better for decreasing the incidence of delayed gastric emptying in modified
      subtotal stomachpreserving pancreaticoduodenectomy. METHODOLOGY: We
      retrospectively analyzed 42 patients who underwent modified subtotal stomach
      preserving pancreaticoduodenectomy with pancreaticogastrostomy. The patients were
      divided into 2 groups based on type of reconstruction: the antecolic
      reconstruction group and the retrocolic reconstruction group. The incidence of
      delayed gastric emptying was determined and compared between the 2 groups.
      RESULTS: The mean time during nasogastric suction and before initiation of a diet
      after surgery was shorter in the retrocolic reconstruction group (without
      significant difference); however, the mean time before oral ingestion of solid
      food could be safely resumed was significantly shorter in the retrocolic
      reconstruction group (9.7+/-1.2 days) than in the antecolic reconstruction group
      AC group (11.4+/-3.0 days; p<0.0112). CONCLUSIONS: We consider retrocolic
      reconstruction preferable to antecolic reconstruction for preventing delayed
      gastric emptying in patients who have undergone modified subtotal-stomach
      preserving pancreaticoduodenectomy with pancreaticogastrostomy.

PMID- 22580681
TI  - Vagus nerve preservation results in visceral fat maintenance after distal
      gastrectomy.
AB  - BACKGROUND/AIMS: Although preservation of the vaguas nerve is recommended in
      surgery for earlystage gastric cancer, the physiological effect of vagotomy on
      the postoperative course has not been well documented. We assessed the effect of
      vagotomy on the change in fat volume after gastrectomy. METHODOLOGY: Subcutaneous
      fat area (SFA) and visceral fat area (VFA) were separately measured in computed
      tomographic images taken before and more than 6 months after surgery, using Fat
      Scan software. The ratios of postoperative/ preoperative values of these two fat
      areas as well as body weight were calculated in 45 patients who underwent DG with
      (n=24) or without (n=21) vagotomy. RESULTS: Vagotomy did not affect the change in
      body weight (91.3+/-1.7% vs. 92.1+/-1.7%). In patients with vagotomy, VFA was
      reduced to 59.0+/-5.1%, which was significantly greater than the reduction in SFA
      (74.3+/-8.7%, p=0.042). In contrast, the reduction ratios of VFA and SFA were
      equal in vagus nerve-preserved patients (78.4+/-6.7% vs. 78.2+/-6.9%, p=0.97).
      CONCLUSIONS: The vagus nerve may have a function to locally regulate the intra
      abdominal fat volume and preservation of the vagus nerve results in the
      maintenance of visceral fat after DG.

PMID- 22580682
TI  - Transarterial embolization with cyanoacrylate for severe arterioportal shunt
      complicated by hepatocellular carcinoma.
AB  - PURPOSE: To evaluate the efficacy and safety of cyanoacrylate glue embolization
      in the treatment of severe arterioportal shunt (APS) presenting with hepatofugal
      portal venous flow in hepatocellular carcinoma (HCC) patients. MATERIALS AND
      METHODS: Between July 2000 and January 2010, 27 HCC patients with severe APS
      presenting with hepatofugal portal venous flow underwent transarterial
      angiography and treatment. Among them, four patients were excluded from the
      study. Twelve patients underwent transarterial chemoperfusion and embolization of
      APS with cyanoacrylate glue between January 2006 and January 2010 (Emb group),
      and the other 11 patients undergoing only transarterial chemoperfusion without
      embolization of APS between July 2000 and December 2005 served as a control group
      (non-Emb group). The change of APS, survival rates, and procedure related
      complications were analyzed. RESULTS: In the Emb group, APS was improved in all
      of the 12 patients after initial glue embolization; long-term APS improvement
      with hepatopetal portal flow was achieved in 80 % (8 of 10) patients who
      underwent follow-up angiography. Survival rates in the Emb group were 67 % at 6
      months, 33 % at 1 year, and 8 % at 2 years, whereas those in the non-Emb group
      were 0 % at 6 months (P < 0.05). Median survival time in the Emb group was 275
      days, which was longer than that of 107 days in the non-Emb group (P = 0.001).
      There were no major complications in both groups. CONCLUSION: The preliminary
      experience suggests that glue embolization may be an effective and safe therapy
      in the management of severe APS accompanied by HCC and also improve patient
      survival.

PMID- 22580683
TI  - Intra-arterial autologous bone marrow cell transplantation in a patient with
      upper-extremity critical limb ischemia.
AB  - Induction of therapeutic angiogenesis by autologous bone marrow mononuclear cell
      transplantation has been identified as a potential new option in patients with
      advanced lower-limb ischemia. There is little evidence of the benefit of intra
      arterial cell application in upper-limb critical ischemia. We describe a patient
      with upper-extremity critical limb ischemia with digital gangrene resulting from
      hypothenar hammer syndrome successfully treated by intra-arterial autologous bone
      marrow mononuclear cell transplantation.

PMID- 22580684
TI  - Why nature chose Mn for the water oxidase in Photosystem II.
AB  - Nature performs a vital but uniquely energetic reaction within Photosystem II (PS
      II), resulting in the oxidation of two water molecules to yield O(2) and bio
      energetic electrons, as reducing equivalents. Almost all life on earth ultimately
      depends on this chemistry, which occurs with remarkable efficiency within a
      tetramanganese and calcium cluster in the photosystem. The thermodynamic
      constraints for the operation of this water oxidising Mn(4)/Ca cluster within PS
      II are discussed. These are then examined in the light of the known redox
      chemistry of hydrated Mn-oxo systems and relevant model compounds. It is shown
      that the latest high resolution crystal structure of cyanobacterial PS II
      suggests an organization of the tetra-nuclear Mn cluster that naturally
      accommodates the stringent requirements for successive redox potential constancy
      with increasing total oxidation state, which the enzyme function imposes. This
      involves one region of the Mn(4)/Ca cluster being dominantly involved with
      substrate water binding, while a separate, single Mn is principally responsible
      for the redox accumulation function. Recent high level computational chemical
      investigations by the authors strongly support this, with a computed pattern of
      Mn oxidation states throughout the catalytic cycle being completely consistent
      with this interpretation. Strategies to design synthetic, bio-mimetic constructs
      utilising this approach for efficient electrolytic generation of hydrogen fuel
      within Artificial Photosynthesis are briefly discussed.

PMID- 22580685
TI  - PirB restricts neuronal regeneration in developing rat brain following hypoxia
      ischemia.
AB  - The inhibitors of axonal regeneration in the myelin sheath are considered to be
      major contributors to the lack of regeneration in the central nervous system
      (CNS) following hypoxic-ischemic (HI) brain damage. As well as the Nogo receptor
      (NgR), the paired-immunoglobulin-like receptor B (PirB) is a functional receptor
      for the myelin inhibitors of axonal regeneration. The inhibition of PirB and NgR
      activities may block most of the inhibitory effects of myelin inhibitors on nerve
      regeneration. We observed the PirB protein and mRNA expression in HI-damaged rat
      cortical neurons using immunohistochemistry and reverse transcription-polymerase
      chain reaction assays. In addition, we treated the HI-damaged rat cortical
      neurons using PirB antibodies to observe the regeneration of injured neurons.
      Moreover, the Rock II activity in HI-damaged rat cortical neurons treated with
      PirB antibodies was observed using western blot analysis. The mRNA and protein
      levels of PirB increased in newborn rat cortical neurons following HI damage.
      Treatment with PirB antibodies is able to improve axonal regeneration following
      HI damage compared with normal axonal growth. Rock II activity also increased in
      the HI-damaged rat brain. The inhibition of PirB is therefore a potential
      therapeutic method to promote the regeneration of HI-damaged axons and the
      inhibitory signal may be transduced through the Rho-ROCK signaling pathway.

PMID- 22580686
TI  - The bps signal: embryonic arrest from an auxin-independent mechanism in bypass
      triple mutants.
AB  - Long-distance signaling is essential for coordination of plant development and
      environmental responses. We originally isolated a tiny mutant named bypass1
      (bps1), which has defects in shoot and root development. The bps1 roots
      overproduce a mobile signal (bps signal) that arrests both root and shoot
      development. Our recent study demonstrated that all three BPS gene family members
      prevent ectopic synthesis of the same bps signal.bps multiple mutants show
      progressively more severe developmental defects. An embryogenesis analysis
      revealed abnormal cell divisions in all meristem lineages of bps triple mutants.
      These defects appear to be auxin independent, and arise prior to changes in PLT1
      and PLT2 expression.

PMID- 22580687
TI  - Inhibition of strigolactones promotes adventitious root formation.
AB  - Roots that form from non-root tissues (adventitious roots) are crucial for
      cutting propagation in the forestry and horticulture industries. Strigolactone
      has been demonstrated to be an important regulator of these roots in both
      Arabidopsis and pea using strigolactone deficient mutants and exogenous hormone
      applications. Strigolactones are produced from a carotenoid precursor which can
      be blocked using the widely available but broad terpenoid biosynthesis blocker,
      fluridone. We demonstrate here that fluridone can be used to promote adventitious
      rooting in the model species Pisum sativum (pea). In addition, in the garden
      species Plumbago auriculata and Jasminium polyanthum fluridone was equally as
      successful at promoting roots as a commercial rooting compound containing NAA and
      IBA. Our findings demonstrate that inhibition of strigolactone signaling has the
      potential to be used to improve adventitious rooting in commercially relevant
      species.

PMID- 22580688
TI  - SymRK and the nodule vascular system: an underground connection.
AB  - Symbiotic legume-rhizobia relationship leads to the formation of nitrogen-fixing
      nodules. Successful nodulation depends on the expression and cross-talk of a
      batttery of genes, among them SymRK (symbiosis receptor-like kinase), a leucine
      rich repeat receptor-like kinase. SymRK is required for the rhizobia invasion of
      root hairs, as well as for the infection thread and symbiosome formation. Using
      immunolocalization and downregulation strategies we have recently provided
      evidence of a new function of PvSymRK in nodulation. We have found that a tight
      regulation of PvSymRK expression is required for the accurate development of the
      vascular bundle system in Phaseolus vulgaris nodules.

PMID- 22580689
TI  - Plant-growth promoting effect of newly isolated rhizobacteria varies between two
      Arabidopsis ecotypes.
AB  - Various rhizobacteria are known for their beneficial effects on plants, i. e.
      promotion of growth and induction of systemic resistance against pathogens. These
      bacteria are categorized as plant growth promoting rhizobacteria (PGPR) and are
      associated with plant roots. Knowledge of the underlying mechanisms of plant
      growth promotion in vivo is still very limited, but interference of bacteria with
      plant hormone metabolism is suggested to play a major role. To obtain new growth
      promoting bacteria, we started a quest for rhizobacteria that are naturally
      associated to Arabidopsis thaliana. A suite of native root-associated bacteria
      were isolated from surface-sterilized roots of the Arabidopsis ecotype Gol-1
      derived from a field site near Golm (Berlin area, Germany). We found several
      Pseudomonas and a Microbacterium species and tested these for growth promotion
      effects on the Arabidopsis ecotypes Gol-1 and Col-0, and for growth-promotion
      associated traits, such as auxin production, ACC deaminase activity and phosphate
      solubilization capacity. We showed that two of the bacteria strains promote plant
      growth with respect to rosette diameter, stalk length and accelerate development
      and that the effects were greater when bacteria were applied to Col-0 compared
      with Gol-1. Furthermore, the capability of promoting growth was not explained by
      the tested metabolic properties of the bacteria, suggesting that further
      bacterial traits are required. The natural variation of growth effects, combined
      with the extensive transgenic approaches available for the model plant
      Arabidopsis, will build a valuable tool to augment our understanding of the
      molecular mechanisms involved in the natural Arabidopsis - PGPR association.

PMID- 22580690
TI  - The epigenetic machinery controlling transgenerational systemic acquired
      resistance.
AB  - Progeny from diseased Arabidopsis shows enhanced resistance, which is associated
      with priming of defense genes. This transgenerational systemic acquired
      resistance (SAR) is effective against biotrophic pathogens, such as the downy
      mildew pathogen Hyaloperonospora arabidopsidis. In this study, we have examined
      mutants in RNA-directed DNA methylation (RdDM) for transgenerational SAR. Our
      analysis suggests that transgenerational SAR is regulated by the RdDM pathway and
      transmitted by hypomethylation at CpNpG sites.

PMID- 22580691
TI  - Looking for the hub in Fe signaling.
AB  - Recently we could demonstrate that FIT is post-translationally regulated in way
      of protein turnover and that such turnover can be counteracted by the signaling
      compound NO. Here we summarize findings about FIT regulation and point out which
      signals and post-translational modifications could act on FIT activity to
      regulate iron uptake from the soil.

PMID- 22580692
TI  - N-rich protein (NRP)-mediated cell death signaling: a new branch of the ER stress
      response with implications for plant biotechnology.
AB  - Upon disruption of ER homeostasis, plant cells activate at least two branches of
      the unfolded protein response (UPR) through IRE1-like and ATAF6-like transducers,
      resulting in the upregulation of ER-resident molecular chaperones and the
      activation of the ER-associated degradation protein system. Here, we discuss a
      new ER stress response pathway in plants that is associated with an osmotic
      stress response in transducing a cell death signal. Both ER and osmotic stress
      induce the expression of the novel transcription factor GmERD15, which binds and
      activates N-rich protein (NRP) promoters to induce NRP expression and cause the
      upregulation of GmNAC6, an effector of the cell death response. In contrast to
      this activation mechanism, the ER-resident molecular chaperone binding protein
      (BiP) attenuates the propagation of the cell death signal by modulating the
      expression and activity of components of the ER and osmotic stress-induced NRP
      mediated cell death signaling. This interaction attenuates dehydration-induced
      cell death and promotes a better adaptation of BiP-overexpressing transgenic
      lines to drought.

PMID- 22580693
TI  - The role of jasmonic acid in root mitochondria disruption.
AB  - Methyl jasmonate (MeJA) produces an important reduction in the accumulation of
      proteins related to energy metabolism. The treatment of hairy roots (HR) with
      MeJA increased the accumulation of H2O2 during the first 48 h and this H2O2
      accumulation was also observed in isolated mitochondria. Peroxidase and catalase
      activities decreased in the presence of MeJA, and this decrease directly
      correlated with the increase of H2O2 in HR treated with MeJA. This suggests that
      the H2O2 burst due to MeJA is the initial response to mitochondria disruption in
      the roots.

PMID- 22580694
TI  - Tomato responds to green peach aphid infestation with the activation of trehalose
      metabolism and starch accumulation.
AB  - The disaccharide trehalose and trehalose-6-phosphate that are present in trace
      amounts are suggested to have a signaling function in plants. Recently, it was
      demonstrated that trehalose metabolism contributes to Arabidopsis thaliana
      defense against the green peach aphid (GPA; Myzus persicae Sulzer), an important
      insect pest of a large variety of plants. TPS11 (TREHALOSE PHOSPHATE SYNTHASE11)
      dependent trehalose metabolism was shown to curtail GPA infestation by promoting
      starch accumulation and expression of the PAD4 (PHYTOALEXIN-DEFICIENT4) gene,
      which has important roles in regulating antibiosis and antixenosis against GPA.
      Here we show that trehalose metabolism is similarly activated in leaves of GPA
      infested tomato (Solanum lycopersicum) plants and likely contributes to tomato
      defense against GPA. GPA-infested leaves of tomato accumulated trehalose, which
      was accompanied by the transient upregulation of SlTPS11, a homolog of the
      Arabidopsis TPS11. GPA-infestation was also accompanied by starch accumulation
      and the upregulation of SlPAD4, the tomato homolog of Arabidopsis PAD4.
      Furthermore, trehalose application induced SlPAD4 expression and starch
      accumulation, and curtailed GPA infestation, suggesting that like in Arabidopsis
      trehalose contributes to tomato defense against GPA.

PMID- 22580695
TI  - Calcium promotes activity and confers heat stability on plant peroxidases.
AB  - In this paper we demonstrate how peroxidase (PO) activities and their heat
      stability correlate with the availability of free Ca(2+) ions. Calcium ions work
      as a molecular switch for PO activity and exert a protective function, rendering
      POs heat stable. The concentration ranges of these two activities differ
      markedly. POs are activated by uM Ca(2+) concentration ranges, whereas heat
      stabilization is observed in the nM range. This suggests the existence of
      different Ca(2+) binding sites. The heat stability of POs depends on the source
      plant species. Terrestrial plants have POs that exhibit higher temperature
      stability than those POs from limnic and marine plants. Different POs from a
      single species can differ in terms of heat stability. The abundance of different
      POs within a plant is dependent on age and developmental stage. The heat
      stability of a PO does not necessarily correlate with the maximum temperature the
      source species is usually exposed to in its natural habitat. This raises
      questions on the role of POs in the heat tolerance of plants. Consequently,
      detailed investigations are needed to identify and characterize individual POs,
      with regard to their genetic origin, subcellular expression, tissue abundance,
      developmental emergence and their functions in innate and acquired heat
      tolerance.

PMID- 22580696
TI  - HD2 proteins interact with RPD3-type histone deacetylases.
AB  - HD2 proteins were previously identified as plant specific histone deacetylases
      (HDACs). The molecular mechanism of the function of HD2 proteins is still
      unclear. Using Bimolecular fluorescence complementation assay, we demonstrated
      that Arabidopsis HD2 proteins, HD2A, HD2C and HD2D, can interact with RPD3-type
      HDACs, HDA6 and HDA19, suggesting that that these proteins may act in the same
      protein complex. Our study indicates that HD2 proteins may functionally associate
      with RPD3-type HDACs to regulate gene expression in plants.

PMID- 22580697
TI  - The role of flavonoids in the establishment of plant roots endosymbioses with
      arbuscular mycorrhiza fungi, rhizobia and Frankia bacteria.
AB  - Flavonoids are a group of secondary metabolites derived from the phenylpropanoid
      pathway. They are ubiquitous in the plant kingdom and have many diverse functions
      including key roles at different levels of root endosymbioses. While there is a
      lot of information on the role of particular flavonoids in the Rhizobium-legume
      symbiosis, yet their exact role during the establishment of arbuscular mycorrhiza
      and actinorhizal symbioses still remains unclear. Within the context of the
      latest data suggesting a common symbiotic signaling pathway for both plant-fungal
      and plant bacterial endosymbioses between legumes and actinorhiza-forming
      fagales, this mini-review highlights some of the recent studies on the three
      major types of root endosymbioses. Implication of the molecular knowledge of
      endosymbioses signaling and genetic manipulation of flavonoid biosynthetic
      pathway on the development of strategies for the transfer and optimization of
      nodulation are also discussed.

PMID- 22580698
TI  - Perspectives in PDK1 evolution: insights from photosynthetic and non
      photosynthetic organisms.
AB  - Protein kinases belonging to the AGC group modulate many diverse cellular
      processes in all eukaryotes. One important way to regulate AGC kinases is through
      phosphorylation by the upstream kinase PDK1. PDK1 localization and activity
      usually depend on interactions with phospholipids, which are mediated by a
      conserved lipid-binding pleckstrin homology (PH) domain. We recently analyzed
      putative PDK1 sequences from 17 photosynthetic organisms, finding that PDK1s from
      vascular and nonvascular species seem to be distinguished by the presence or
      absence of a PH domain, respectively. The only other reported PDK1 lacking a PH
      domain is from yeast (Saccharomyces cerevisiae). These observations raise
      questions about how plant PDK1s and their lipid-binding capabilities have evolved
      in relation to other eukaryotes, and what this means for PDK1 function. Here we
      use 100 PDK1 sequences from diverse organisms to discuss possible evolutionary
      aspects of plant PDK1 structure and lipid binding.

PMID- 22580699
TI  - ATI1, a newly identified atg8-interacting protein, binds two different Atg8
      homologs.
AB  - Autophagy is a mechanism used for the transport of macromolecules to the vacuole
      for degradation. It can be either non-selective or selective, resulting from the
      specific binding of target proteins to Atg8, an essential autophagy-related
      protein. Nine Atg8 homologs exist in the model plant Arabidopsis thaliana,
      suggesting possible different roles for different homologs. In a previous report
      published in the Plant Cell, our group identified two plant-specific proteins,
      termed ATI1 and ATI2, which bind Atg8f, as a representative of the nine Atg8
      homologs. The proteins were shown to associate with novel starvation-induced
      bodies that move on the ER network and reach the lytic vacuole. Altered
      expression level of the proteins was also shown to affect the ability of seeds to
      germinate in the presence of the germination inhibiting hormone ABA. In the
      present addendum article, we demonstrate that, in addition to Atg8f, ATI1 binds
      Atg8h, an Atg8 homolog from a different sub-family, indicating that ATI1 is not a
      specific target of Atg8f.

PMID- 22580700
TI  - Integrating two patterning processes in the flower.
AB  - Spatial organ arrangement plays an important role in flower development. The
      position and the identity of floral organs is influenced by various processes, in
      particular the expression of MADS-box transcription factors for identity and
      dynamics of the plant hormone auxin for positioning. We are currently integrating
      patterning processes of MADS and auxin into our computational models, based on
      interactions that are known from experiments, in order to get insight in how
      these define the floral body plan. The resulting computational model will help to
      explore hypothetical interactions between the MADS and auxin regulation networks
      in floral organ patterning.

PMID- 22580701
TI  - Apoplastic calcium executes a shut-down function on plant peroxidases: a
      hypothesis.
AB  - Recently it was demonstrated that PO activity is switched by calcium within the
      typical range of apoplastic free calcium concentrations (Plieth and Vollbehr,
      Plant Signal Behav 2012;7: 650-660). The heat stability of POs is also dependent
      on calcium. Here, a scenario is put forward which assigns calcium a switch-off
      function under heat: Peroxidases are switched off by heat stress-triggered
      apoplastic calcium depletion. It is assumed that this initiates apoplastic
      accumulation of reactive oxygen species (ROS) and eventually triggers a self
      amplifying cascade of cellular events involving plasma membrane ion transport.
      Calcium depletion-initiated ROS accumulation (CaDIRA) may also trigger signal
      percolation and the formation of systemic responses to many different stress
      factors in plants. This hypothesis can explain some as yet unexplained
      observations.

PMID- 22580702
TI  - Epigenetic interplay of histone modifications and DNA methylation mediated by
      HDA6.
AB  - One of the most fundamental questions in the control of gene expression is how
      epigenetic patterns of DNA methylation and histone modifications are established.
      Our recent studies demonstrate that histone deacetylase HDA6 integrates DNA
      methylation and histone modifications in gene silencing by interacting with DNA
      methyltransferase MET1 and histone demethylase FLD, suggesting that regulatory
      crosstalk between histone modifications and DNA methylation could be mediated by
      the interaction of various epigenetic modification proteins.

PMID- 22580703
TI  - TOR pathway activation in Zea mays L. tissues: conserved function between animal
      and plant kingdoms.
AB  - In most non-photosynthetic eukaryotes it has been demonstrated a conserved signal
      transduction pathway, namely TOR-S6K, that coordinates growth and cell
      proliferation. This pathway targets the translational apparatus to induce
      selective translation of ribosomal mRNAs as well as stimulate the cell cycle
      transition through the G1/S phase. Thus, by activation of this pathway through
      environmental signals, nutrients, stress, or specific growth factors, such as
      insulin or insulin-like growth factors (IGF), this pathway allows organisms to
      regulate growth and cell division. In plants, evidence has shown that TOR protein
      has been highly conserved through evolution, being involved in growth and cell
      proliferation control as well. Particularly in maize, a peptide named ZmIGF has
      been found in actively growing tissues. It targets the maize TOR pathway at the
      same extent as insulin and, by doing so it induces growth, as well as ribosomal
      proteins and DNA synthesis. Thus, higher metazoans and plants seem to conserve
      similar biochemical paths to regulate cell growth through equivalent targets that
      conduce to activation of the TOR-S6K pathway. Recent research shows evidence that
      supports this proposal by uncovering the ZmIGF receptor in maize, providing
      further means for analyzing the role of the conserved TOR signaling pathway in
      this plant.

PMID- 22580704
TI  - Toward a unified model of the action of CLP/HSP100 chaperones in chloroplasts.
AB  - In chloroplasts, Hsp70 and Hsp100 chaperones have been long suspected to be the
      motors that provide the necessary energy for the import of precursor proteins
      destined to the organelle. The chaperones associate with the import translocon
      and meet the transit peptides as they emerge through the channel. After decades
      of active research, recent findings demonstrated that Hsp100 chaperones recognize
      transit peptides both in vitro and in vivo. Moreover, Hsp70 also plays a part in
      precursor import. The updated model of protein translocation into chloroplasts
      now presents new questions about the role of the chaperones in the process.

PMID- 22580705
TI  - Plastids and pathogens: mechanosensitive channels and survival in a hypoosmotic
      world.
AB  - In bacteria, MscS-type mechanosensitive channels serve to protect cells from
      lysis as they swell during extreme osmotic stress. We recently showed that two
      MscS homologs from Arabidopsis thaliana serve a similar purpose in the epidermal
      plastids of the leaf, indicating that the plant cell cytoplasm can present a
      dynamic osmotic challenge to the plastid. MscS homologs are predicted to be
      targeted to both plastids and mitochondrial envelopes and have been found in the
      genomes of intracellular pathogens. Here we discuss the implications of these
      observations, and propose that MS channels provide an essential mechanism for
      osmotic adaptation to both intracellular and the extracellular environments.

PMID- 22580706
TI  - CBSXs are sensor relay proteins sensing adenosine-containing ligands in
      Arabidopsis.
AB  - We recently determined that CBSX proteins, which have only one pair of
      cystathionine beta-synthase (CBS) domains, directly regulate the activation of
      thioredoxins and thereby control cellular H2O2 levels and modulate both plant
      development and growth. The Arabidopsis genome contains six CBSXs, and these are
      localized to different subcellular compartments- CBSX1 and CBSX2 in the
      chloroplast, CBSX3 in the mitochondria, CBSX4 in the cytosol, and CBSX5 and CBSX6
      in the endoplasmic reticulum. The CBSXs have been identified in prokaryotes and
      plants, but not in animals. The considerable differences in length and amino acid
      sequence between CBSX members may result in variations in protein structure and
      in their specificity to interact with ligands and/or target proteins. Here, we
      discuss the possibility that the CBSXs are novel sensor relay proteins that use
      adenosine-containing molecules as a ligand.

PMID- 22580707
TI  - Regulation of reactive oxygen species generation under drought conditions in
      Arabidopsis.
AB  - Reactive oxygen species (ROS) are produced when plants are exposed to
      environmental stresses, such as drought and heat conditions. Oxidative stress
      imposed by ROS under drought conditions profoundly affects plant growth and
      development. However, ROS production and scavenging mechanisms under adverse
      environmental conditions are largely unknown. We have recently reported that a
      NAM/ATAF1/2/CUC2 (NAC) transcription factor NTL4 is required for generation of
      ROS under drought conditions in Arabidopsis. 35S:4DeltaC transgenic plants
      overexpressing a truncated NTL4 form (4DeltaC) lacking the C-terminal
      transmembrane (TM) motif were hypersensitive to drought stress, and ROS
      accumulated to a high level in the transgenic plants. In contrast, NTL4-deficient
      ntl4 mutants were less sensitive to drought stress and contained reduced levels
      of ROS. Furthermore, the plasma membrane-associated NTL4 transcription factor is
      proteolytically activated by treatments with drought and abscisic acid (ABA) and
      nuclear-localized, where it induces expression of NADPH oxidase genes involved in
      ROS biosynthesis. Notably, the 35S:4DeltaC transgenic plants showed accelerated
      leaf senescence and cell death under drought conditions. Taken together, these
      observations indicate that NTL4 regulation of ROS generation underlies the
      drought-induced leaf senescence.

PMID- 22580708
TI  - Illuminating the wall: using click chemistry to image pectins in Arabidopsis cell
      walls.
AB  - Plant cell walls are the most abundant biomaterials on Earth and serve a
      multitude of purposes in human society. These complex extracellular matrices are
      mainly composed of polysaccharides, including cellulose, hemicelluloses, and
      pectins, which cannot be cytologically examined using conventional techniques.
      Click chemistry, which exploits a bio-orthogonal cycloaddition reaction between
      alkynyl and azido groups, has proven to be useful for the metabolic incorporation
      and detection of modified sugars in polysaccharides in animals, fungi, and
      bacteria, but its use to interrogate the biosynthesis or dynamics of plant cell
      walls has not been previously reported. Recently, we found that an alkynylated
      analog of fucose can be metabolically incorporated into Arabidopsis thaliana cell
      walls and click labeled with fluorescent probes, facilitating imaging of cell
      wall carbohydrates. Despite the presence of fucose in several classes of wall
      polysaccharides, fucose-alkyne was primarily incorporated into rhamnogalacturonan
      I, a type of pectin. Using timecourse and pulse-labeling experiments, we observed
      the dynamics of pectin delivery and reorganization in expanding cell walls. The
      use of click chemistry to investigate plant cell wall architecture should help
      bridge the gap between biochemical characterization of isolated cell wall
      components and an understanding of how those components interact in intact cell
      walls.

PMID- 22580709
TI  - Analysis of adaptive ribosomal gene diversity in wild plant populations from
      contrasting climatic environments.
AB  - Plant populations may contain variation that reflects adaptation to local
      environmental conditions. Clues to adaptive evolution of plants may be found in
      the genomes of species growing in diverse environments or across steep
      environmental gradients, and under stress. We have examined populations of wild
      relatives of barley and rice across diverse environmental gradients. Greater
      diversity, in a nuclear biotic stress defense gene and in chloroplast genes, was
      found in the more stressed, hotter and dryer environments. This may reflect the
      greater heterogeneity of these environments. Adaptation of plants to different
      abiotic stresses (temperatures and levels of water availability) may also require
      significant adaptation to the different biotic (pest and disease) pressures in
      these environments.

PMID- 22580711
TI  - FTY720 induces cell cycle arrest and apoptosis of rat glomerular mesangial cells.
AB  - The present study aimed to examine the effect of FTY720, a new immunosuppressive
      agent, on the proliferation and apoptosis of glomerular mesangial cells (GMC),
      and investigate the underlying mechanisms. Cultured rat GMC were treated by
      FTY720, and the cell viability, apoptosis and cell cycle progression were
      examined. Furthermore, cell cycle related gene expression profile was analyzed by
      cDNA microarray, and the protein expression of cell cycle related genes as well
      as Bax and Bcl-2 were examined by Western blot. The results showed that FTY720
      inhibited GMC proliferation and induced apoptosis of GMC in a dose- and time
      dependent manner, and induced G(1) phase cell cycle arrest in GMC in a dose
      dependent manner as well. cDNA microarray analysis revealed that FTY720 regulated
      the expression of cell cycle-related gene. Western blot analysis showed that
      FTY720 induced the downregulation of cyclin D1, cyclin E, CDK2, CDK4, Bcl-2 and
      E2F1 and the upregulation of Kip1/p27, Cip1/p21, Bax and Rb in GMC in a dose
      dependent manner. These results demonstrated that FTY720 could inhibit the
      proliferation of GMC through inducing cell cycle arrest and apoptosis, probably
      via the regulation of the expression of cell cycle-related genes and Bax/Bcl-2.

PMID- 22580710
TI  - The DTNBP1 (dysbindin-1) gene variant rs2619522 is associated with variation of
      hippocampal and prefrontal grey matter volumes in humans.
AB  - DTNBP1 is one of the most established susceptibility genes for schizophrenia, and
      hippocampal volume reduction is one of the major neuropathological findings in
      this severe disorder. Consistent with these findings, the encoded protein
      dysbindin-1 has been shown to be diminished in glutamatergic hippocampal neurons
      in schizophrenic patients. The aim of this study was to investigate the effects
      of two single nucleotide polymorphisms of DTNBP1 on grey matter volumes in human
      subjects using voxel-based morphometry. Seventy-two subjects were included and
      genotyped with respect to two single nucleotide polymorphisms of DTNBP1
      (rs2619522 and rs1018381). All participants underwent structural magnetic
      resonance imaging (MRI). MRI data were preprocessed and statistically analysed
      using standard procedures as implemented in SPM5 (Statistical Parametric
      Mapping), in particular the voxel-based morphometry (VBM) toolbox. We found
      significant effects of the DTNBP1 SNP rs2619522 bilaterally in the hippocampus as
      well as in the anterior middle frontal gyrus and the intraparietal cortex.
      Carriers of the G allele showed significantly higher grey matter volumes in these
      brain regions than T/T homozygotes. Compatible with previous findings on a role
      of dysbindin in hippocampal functions as well as in major psychoses, the present
      study provides first direct in vivo evidence that the DTNBP1 SNP rs2619522 is
      associated with variation of grey matter volumes bilaterally in the hippocampus.

PMID- 22580712
TI  - Influences of charcoal and bamboo charcoal amendment on soil-fluoride fractions
      and bioaccumulation of fluoride in tea plants.
AB  - High levels of fluoride in tea plants pose a potential health risk to humans who
      drink tea. It has been demonstrated that tea plant fluoride is closely related to
      the available fluoride in soil. But approaches that could be used to regulate the
      availability of fluoride in soil have been rarely seen. This study aims to
      investigate how the addition of charcoal and bamboo charcoal affected soil
      fluoride availability and bioaccumulation of fluoride in tea plants. In a
      microcosm experiment, tea plants were grown in the tea garden soil mixed with
      different amounts of charcoal and bamboo charcoal [that is, 0.5, 1.0, 2.5, and
      5.0 % (w/w)]. Soil-fluoride fractions and fluoride accumulated in tea plants were
      determined using the sequential extraction and ion selective electrode method.
      Obtained results showed that both charcoal and bamboo charcoal additions
      significantly enhanced the concentrations of Fe/Mn oxide-bound fluoride, but
      significantly reduced the concentrations of water-soluble and exchangeable
      fluoride (p < 0.05) in soil. Charcoal and bamboo charcoal additions also
      significantly decreased the amounts of fluoride in tea roots and tea leaves (p <
      0.05). However, the additions of charcoal and bamboo charcoal had no impacts on
      the tea quality, as indexed by the concentrations of polysaccharides,
      polyphenols, amino acids, and caffeine in tea leaves. These results suggested
      that application of charcoal and bamboo charcoal may provide a useful method to
      reduce the availability of fluoride in soil and the subsequent fluoride uptake by
      tea plants.

PMID- 22580713
TI  - Novel quercetin glucosides from Helminthostachys zeylanica root and acceleratory
      activity of melanin biosynthesis.
AB  - Two novel quercetin glucosides, namely 4'-O-beta-D-glucopyranosyl-quercetin-3-O
      beta-D-glucopyranosyl-(1->4)-beta-D-glucopyranoside (compound 1) and 4'-O-beta-D
      glucopyranosyl-(1->2)-beta-D-glucopyranosyl-quercetin-3-O-beta-D-glucopyranosyl
      (1->4)-beta-D-glucopyranoside (compound 2), were isolated from Helminthostachys
      zeylanica root 50 % EtOH extract. Structural analysis of isolated compounds was
      achieved mainly by 600 MHz and 800 MHz NMR, UPLC-TOFMS and GC-MS. Of the two
      quercetin glucosides, compound 1 showed a high melanogenic acceleratory effect,
      2.7 times higher than control, at 10 MUM concentration in murine B16 melanoma
      cells, with no cytotoxic effect.

PMID- 22580714
TI  - Canine left ventricle electromechanical behavior under different pacing modes.
AB  - BACKGROUND: Cardiac resynchronization therapy may improve survival and quality of
      life in patients suffering from heart failure with left ventricular (LV)
      contraction dyssynchrony. While several studies have investigated electrical or
      mechanical determinants of synchronous contraction, few have focused on
      activation contraction coupling at a macroscopic level. OBJECTIVE: The objective
      of the study was to characterize LV electromechanical behavior and response to
      pacing in a heart failure model. METHODS: We analyzed data from 3D
      electroanatomic non-contact mapping and blood pool SPECT for 12 dogs with right
      ventricular (RV) tachycardia pacing-induced dilated cardiomyopathy. Surfaces
      generated by the two modalities were registered. Electrical signals were
      analyzed, and endocardial wall displacement curves were portrayed. RESULTS: Rapid
      pacing decreased the mean LV ejection fraction (LVEF) to 20.9 % and prolonged the
      QRS duration to 79 +/- 10 ms (normal range: 40-50 ms). QRS duration remained
      unchanged with biventricular pacing (88.5 ms), while single site pacing further
      prolonged the QRS duration (113.3 ms for RV pacing and 111.6 ms for LV pacing).
      No trend was observed in LV systolic function. Activation duration time was
      significantly increased with all pacing modes compared to baseline. Finally,
      electromechanical delay, as defined by the delay between electrical activation
      and mechanical response, was increased by single site pacing (172.9 ms for RV
      pacing and 174.6 ms for LV pacing) but not by biventricular pacing (162.4 ms).
      CONCLUSIONS: Combined temporal and spatial coregistration electroanatomic maps
      and baseline gated blood pool SPECT imaging allowed us to quantify activation
      duration time, electromechanical delay, and LVEF for different pacing modes. Even
      if pacing modes did not significantly modify LVEF or activation duration, they
      produced alterations in electromechanical delay, with biventricular pacing
      significantly decreasing the electromechanical delay as measured by surface
      tracings and endocardial non-contact mapping.

PMID- 22580715
TI  - Pacing polarity and left ventricular mechanical activation sequence in cardiac
      resynchronization therapy.
AB  - OBJECTIVE: The aim of this study is to evaluate the relationship between polarity
      of left ventricular (LV) pacing and the resultant regional, global, and
      transmural mechanical sequence of contraction. BACKGROUND: Cardiac
      resynchronization therapy (CRT) is widely utilized in patients with drug
      refractory congestive heart failure with systolic dysfunction (EF <35 %) and
      intraventricular conduction delay (QRS duration >120 ms). However, little is
      known about polarity of pacing stimulation and the resultant differences in LV
      mechanics. METHODS: The polarity of pacing was altered sequentially in 20
      patients (73 +/- 13, 16 males) with preexisting biventricular devices with
      potential choice of multiple vectors for pacing stimulation. Initial unipolar or
      extended bipolar configurations were switched to bipolar configuration or vice
      versa, and echocardiographic images were acquired for off-line analysis. Regional
      and global LV longitudinal and radial mechanics were assessed selectively from
      the subendocardial and subepicardial regions with 2D speckle-tracking
      echocardiography. Left ventricular capture by each vector configuration was
      confirmed by local lead capture and appropriate QRS alteration. RESULTS: Unipolar
      pacing resulted in increased dispersion of LV regional endocardial strains with a
      higher base-to-apex gradients of longitudinal shortening strains (P < 0.05). LV
      longitudinal shortening strain magnitude was higher at LV base with bipolar
      stimulation in comparison with unipolar stimulation (-10.5 +/- 10.5 vs. -4.2 +/-
      6.3, P = 0.02). CONCLUSION: There is a difference in the mechanical activation
      sequence of the LV between unipolar vs. bipolar pacing stimulation. This may have
      important implications for CRT.

PMID- 22580716
TI  - Innate immune activation in neonatal tracheal aspirates suggests endotoxin-driven
      inflammation.
AB  - BACKGROUND: Tracheal aspirates (TAs) from critically ill neonates accumulate
      bacterial endotoxin and demonstrate mobilization of endotoxin-binding proteins,
      but the potential bioactivity of endotoxin in TAs is unknown. We characterized
      innate immune activation in TAs of mechanically ventilated neonates. METHODS:
      Innate immune activation in TAs of mechanically ventilated neonates was
      characterized using a targeted 84-gene quantitative real-time (qRT) PCR array.
      Protein expression of cytokines was confirmed by multiplex assay. Expression and
      localization of the endotoxin-inducible antimicrobial protein Calgranulin C
      (S100A12) was assessed by flow cytometry. Endotoxin levels were measured in TA
      supernatants using the Limulus amoebocyte lysate assay. RESULTS: Analyses by qRT
      PCR demonstrated expression of pattern recognition receptors, Toll-like receptor
      nuclear factor kappaB and inflammasome pathways, cytokines/chemokines and their
      receptors, and anti-infective proteins in TA cells. Endotoxin positivity
      increased with postnatal age. As compared with endotoxin-negative TAs, endotoxin
      positive TAs demonstrated significantly greater tumor necrosis factor (TNF),
      interleukin (IL)-6, IL-10, and serpin peptidase inhibitor, clade E, member 1
      (SERPINE1) mRNA, and IL-10, TNF, and IL-1beta protein. Expression of S100A12
      protein was localized to TA neutrophils. CONCLUSION: Correlation of endotoxin
      with TA inflammatory responses suggests endotoxin bioactivity and the possibility
      that endotoxin antagonists could mitigate pulmonary inflammation and its sequelae
      in this vulnerable population.

PMID- 22580717
TI  - Evolution of the urinary proteome during human renal development and maturation:
      variations with gestational and postnatal age.
AB  - BACKGROUND: Low birth weight is associated with deficits in nephron number in the
      infant kidney and increased risk of adulthood hypertension and renal dysfunction.
      Urinary biomarkers may be potential indicators of renal reserve, but little is
      known about the influence of gestational and postnatal age on the expression of
      urinary proteins. The aims of this study were to determine the relationships
      between selected urinary proteins and renal maturation. We hypothesized that
      urinary protein patterns would change over time during late nephrogenesis and
      renal maturation. METHODS: Urine samples were collected at birth and over 12 mo
      from preterm (33-35 wk) and term (38-40 wk) infants. Candidate urinary proteins
      were identified by antibody array and quantified with enzyme-linked immunosorbent
      assay. RESULTS: Preterm infants at birth were found to have relatively elevated
      levels of insulin-like growth factor binding protein-1, -2, and -6, monocyte
      chemotactic protein-1, CD14, and sialic acid-binding Ig-like lectin 5. These
      markers gradually decline to levels similar to those of full-term infants by 2-6
      mo of life. In contrast, many urinary markers in healthy full-term infants remain
      stable over the first year of life. CONCLUSION: Gestational and postnatal age
      must be considered when evaluating the utility of urinary biomarkers.

PMID- 22580718
TI  - Neurally adjusted ventilatory assist improves patient-ventilator interaction in
      infants as compared with conventional ventilation.
AB  - BACKGROUND: Neurally adjusted ventilatory assist (NAVA) is a mode of ventilation
      controlled by the electrical activity of the diaphragm (Edi). The aim was to
      evaluate patient-ventilator interaction in infants during NAVA as compared with
      conventional ventilation. METHODS: Infants were successively ventilated with
      NAVA, pressure control ventilation (PCV), and pressure support ventilation (PSV).
      Edi and ventilator pressure (Pvent) waveforms were compared and their variability
      was assessed by coefficients of variation. RESULTS: Ten patients (mean age 4.3 +/
      2.4 mo and weight 5.9 +/- 2.2 kg) were studied. In PCV and PSV, 4 +/- 4.6% and
      6.5 +/- 7.7% of the neural efforts failed to trigger the ventilator. This did not
      occur during NAVA. Trigger delays were shorter with NAVA as compared with PCV and
      PSV (93 +/- 20 ms vs. 193 +/- 87 ms and 135 +/- 29 ms). During PCV and PSV, the
      ventilator cycled off before the end of neural inspiration in 12 +/- 13% and 21
      +/- 19% of the breaths (0 +/- 0% during NAVA). During PCV and PSV, 24 +/- 11% and
      25 +/- 9% of the neural breath cycle was asynchronous with the ventilator as
      compared with 11 +/- 3% with NAVA. A large variability was observed for Edi in
      all modes, which was transmitted into Pvent during NAVA (coefficient of
      variation: 24 +/- 8%) and not in PCV (coefficient of variation 2 +/- 1%) or PSV
      (2 +/- 2%). CONCLUSION: NAVA improves patient-ventilator interaction and delivers
      adequate ventilation with variable pressure in infants.

PMID- 22580719
TI  - UGT1A1, SLCO1B1, and SLCO1B3 polymorphisms vs. neonatal hyperbilirubinemia: is
      there an association?
AB  - BACKGROUND: Jaundice is a physiological phenomenon; however, severe
      hyperbilirubinemia occurs in only 5 to 6% of the healthy newborn population. It
      has been suggested that genetic variation could enhance the risk of
      hyperbilirubinemia when coexpressed with other icterogenic conditions. METHODS:
      The study included newborns with a gestational age of greater than 35 wk and
      weights greater than 2,000 g with indications for phototherapy. The polymorphisms
      from UGT1A1 (rs8175347), SLCO1B1 (rs4149056 and rs2306283), and SLCO1B3
      (rs17680137 and rs2117032) were analyzed by capillary electrophoresis and
      hydrolysis probes. RESULTS: A total of 167 hyperbilirubinemic infants and 247
      control subjects were enrolled. The gender, ABO incompatibility, birth weight,
      and gestational age differed between the groups, but the allelic and genotypic
      frequency of the polymorphisms from SLCO1B genes did not. In logistic regression,
      the ABO incompatibility, gestational age, and polymorphic T allele of rs2117032
      remained in the model. The presence of this polymorphism seemed to provide
      protection from hyperbilirubinemia. The individuals who were homozygous for the G
      allele of rs2306283 and who were glucose 6-phosphate-dehydrogenase deficient were
      more frequent among the cases. CONCLUSION: Although genetic variation accounts
      for a good part of this condition, the association between different
      polymorphisms and environmental factors has yet to be explained.

PMID- 22580720
TI  - Intrauterine fetal demise can be remote from the inciting insult in an animal
      model of hypoxia-ischemia.
AB  - BACKGROUND: Fetal hypoxia-ischemia (H-I) results in significant morbidity and
      mortality. Little is known about the timing of death in human stillbirths. The
      vulnerability of the fetus varies with age at the time of insult, but it is
      unknown what happens to the timing of fetal death in relation to a fetal insult.
      We asked the question of whether the timing of fetal death was influenced by the
      age at which the insult occurred. METHODS: Fetal H-I was achieved at three ages
      by sustained uterine ischemia in rabbits, mimicking the acute placental
      insufficiency of placental abruption. RESULTS: H-I at 22 d gestation (E22)
      resulted in fewer perinatal deaths than at E25 and E29. Fetal deaths were grouped
      into early and late perinatal deaths. Early perinatal death mostly occurred
      immediately after H-I and these fetuses delivered before term. Late perinatal
      death occurred between the insult and delivery at term gestation. Early perinatal
      death occurred more often in the E25 hypoxic-ischemic group as compared with
      those of the E22 hypoxic-ischemic group. CONCLUSION: There is an increasing
      vulnerability to hypoxia with increasing gestational age. Perinatal deaths may
      occur long after the episode of H-I. The timing of an intrauterine hypoxic
      ischemic event cannot be inferred from the detection of fetal death.

PMID- 22580721
TI  - Neonatal seizures and postneonatal epilepsy: a 7-y follow-up study.
AB  - BACKGROUND: Seizures are one of the most common symptoms of acute neurological
      disorders in newborns. This study aimed at evaluating predictors of epilepsy in
      newborns with neonatal seizures. METHODS: We recruited consecutively 85 neonates
      with repeated neonatal video-electroencephalogram (EEG)-confirmed seizures
      between January 1999 and December 2004. The relationship between clinical, EEG,
      and ultrasound (US) data in the neonatal period and the development of
      postneonatal epilepsy was investigated at 7 y of age. RESULTS: Fifteen patients
      (17.6%) developed postneonatal epilepsy. Partial or no response to anticonvulsant
      therapy (odds ratio (OR) 16.7, 95% confidence interval (CI): 1.8-155.8, P = 0.01;
      OR 47, 95% CI: 5.2-418.1, P < 0.01, respectively), severely abnormal cerebral US
      scan findings (OR: 5.4; 95% CI: 1.1-27.4; P < 0.04), severely abnormal EEG
      background activity (OR: 9.5; 95% CI: 1.6-54.2; P = 0.01), and the presence of
      status epilepticus (OR: 6.1; 95% CI: 1.8-20.3; P < 0.01) were found to be
      predictors of epilepsy. However, only the response to therapy seemed to be an
      independent predictor of postneonatal epilepsy. CONCLUSION: Neonatal seizures
      seem to be related to postneonatal epilepsy. Recurrent and prolonged neonatal
      seizures may act on an epileptogenic substrate, causing further damage, which is
      responsible for the subsequent clinical expression of epilepsy.

PMID- 22580722
TI  - Effect of light exposure on metalloporphyrin-treated newborn mice.
AB  - BACKGROUND: Neonatal hyperbilirubinemia arises from increased bilirubin
      production and decreased bilirubin elimination. Although phototherapy safely and
      effectively reduces bilirubin levels, recent evidence shows that it has adverse
      effects. Therefore, alternative treatments are warranted. Metalloporphyrins,
      competitive inhibitors of heme oxygenase (HO), the rate-limiting enzyme in
      bilirubin production, effectively reduce bilirubin formation; however, many are
      photoreactive. Here, we investigated possible photosensitizing effects of
      chromium mesoporphyrin (CrMP) and zinc deuteroporphyrin bis-glycol (ZnBG).
      METHODS AND RESULTS: Administration of CrMP or ZnBG to 3-d-old mouse pups (3.75
      30.0 MUmol/kg intraperitoneally) and exposure to cool white (F20T12CW) and blue
      (TL20W/52) fluorescent lights (+L) for 3 h, resulted in a dose-dependent
      mortality (50% lethal dose (LD50) = 21.5 and 19.5 MUmol/kg, respectively). In
      contrast to ZnBG, there was no significant difference in survival between the
      CrMP+L and CrMP groups. Following 30 MUmol/kg ZnBG+L, we found significant weight
      loss, decreased liver antioxidant capacities, and increased aspartate
      aminotransaminase levels. At 6-d post-light exposure, ZnBG+L-treated pups showed
      gross and histologic skin changes at doses >7.5 MUmol/kg. No lethality was
      observed following treatment with 30 MUmol ZnBG/kg plus exposure to blue light
      emitting diodes. Phototoxicity of ZnBG was dependent on light source, emission
      spectrum, and irradiance. CONCLUSION: Low doses of ZnBG (<3.75 MUmol/kg) retained
      maximal HO inhibitory potency without photosensitizing effects, and therefore are
      potentially useful in treating neonatal hyperbilirubinemia.

PMID- 22580723
TI  - The role of taurine in renal disorders.
AB  - This article examines the actions of taurine on models of renal dysfunction, the
      potential mechanisms of taurine action and the possible clinical significance of
      these findings. Our laboratory has written previously on the role of taurine in
      renal function and we have focused upon the normal physiology of the kidney and
      on the mechanisms and regulation of the renal transport of taurine. This review
      is a distinct change of emphasis in that we describe a number of studies which
      have evaluated various aspects of renal dysfunction, including hypertension and
      proteinuria, specific glomerular and tubular disorders, acute and chronic renal
      conditions, urinary tract conditions including infection and nephrolithiasis, and
      diabetic nephropathy. The subject of chronic kidney disease and renal
      transplantation will also be examined relative to beta amino acid. The studies
      evaluated will be mainly recent ones, recognizing that older reviews of the role
      of this taurine in the kidney are available.

PMID- 22580724
TI  - [Adrenal gland surgery: tailored approach].

PMID- 22580725
TI  - [Function-preserving adrenalectomy for adrenal tumors].
AB  - Organ preserving resection (subtotal adrenalectomy) or adrenocortical
      autotransplantation can preserve adrenocortical stress capacity in bilateral
      adrenal surgery. After adrenocortical autotransplantation approximately 30% of
      patients do not need exogenous steroids. Organ preserving surgery avoids steroid
      supplementation in more than 80% of cases. After organ preserving resections in
      secondary or familial diseases, however, there is a relevant risk of recurrent
      disease: the rate of ipsilateral recurrence in familial pheochromocytoma is
      approximately 20% during a follow-up of 20 years. Routine administration of
      exogenous steroids should be avoided after subtotal adrenalectomy as functional
      restitution of the residual tissue might be disturbed. Approximately 80% of
      patients, however, present with impaired adrenocortical stress capacity directly
      after surgery. Within a few weeks some 80% of patients show a sufficient
      functional restitution of the adrenocortical stress capacity. Organ preserving
      adrenal surgery should be performed endoscopically. The adrenal remnant should
      not be devascularized; the adrenal vein, however, can be divided without
      functional consequences. About one third of a normal adrenal gland usually
      provides sufficient adrenocortical function.

PMID- 22580726
TI  - Beta-cell preservation...Is weight loss the answer?
AB  - Obesity is associated with an increased risk of type 2 diabetes (T2D). Pancreatic
      beta-cell failure is an early event in the development of glucose dysregulation
      and diabetes. Interventions to halt beta-cell failure in T2D include diet
      modification, exercise, and use of pharmacologic agents. There is evidence that
      abdominal obesity may contribute to diabetes through insulin resistance and beta
      cell impairment. Pivotal long-term studies into the prevention of T2D have shown
      the importance of weight loss beside diet, lifestyle, and medication. The Finnish
      Diabetes Prevention Program (DPP) showed that weight loss gradually reduces the
      risk of diabetes, and that even modest weight loss can significantly reduce the
      incidence of T2D. Similarly, in the US DPP, weight loss as part of intensive
      lifestyle modification was the major factor in reducing the incidence of T2D in
      high-risk subjects, being more effective than drug intervention. While
      understanding the relationship between obesity and diabetes is complex, we know
      that weight loss has positive effects on adipose tissue. It causes an increase in
      the beneficial fat cell hormone adiponectin, and a decrease in adipose tissue
      inflammation. Also, it is associated with reduced insulin resistance and a
      consequential reduction in glucolipotoxicity, which can improve beta-cell
      function. In summary, weight loss improves glycemic control and thereby mitigates
      diabetes symptoms and complications, possibly through the preservation of beta
      cell function. Therefore, efforts to prevent diabetes and preserve beta-cell
      function in patients with T2D should more consequently emphasize and target
      weight loss.

PMID- 22580728
TI  - Health care access and prevalence of the metabolic syndrome among elders living
      in high-altitude areas of the Mediterranean islands: the MEDIS study.
AB  - AIM: The aim of the present work was to evaluate the relationships between
      sociodemographic, clinical, and lifestyle characteristics and the presence of
      metabolic syndrome, among high and low altitude living elderly individuals
      without known CVD. METHODS: During 2005-2011, 1959 elderly (aged 65 to 100 years)
      individuals from 13 Mediterranean islands were enrolled. Sociodemographic,
      clinical, and lifestyle factors were assessed using standard procedures.
      Metabolic syndrome was defined according to the (Adult Treatment Panel) ATP III
      criteria. Mountainous areas were defined those more than 400 meters in height.
      RESULTS: For the present analysis 713 men and 596 women were studied; the
      prevalence of the metabolic syndrome was 29% (24% in men, 35% in women, p <
      0.001). Furthermore, the prevalence of metabolic syndrome was 55% in the elders
      living in mountainous areas, as compared with 26% among those living at sea-level
      (p = 0.01). Similarly, the prevalence of hypertension, hypercholesterolemia, and
      obesity were higher in high altitude as compared with low altitude areas (all p
      values < 0.01). After adjusting for various confounders, elders living in high
      altitude areas were 3.06-times more likely to have the metabolic syndrome than
      those living at sea-level (OR = 3.06, 95%CI 2.02-4.65). However, when the annual
      number of visits to health care centers was taken into account, the effect of
      altitude of living was not associated with the presence of the syndrome.
      CONCLUSIONS: A considerable proportion of mountainous living elderly had the
      metabolic syndrome. Public health actions need to be taken to reduce the burden
      of cardiometabolic disorders by enabling better access to health care, especially
      in remote mountainous rural areas.

PMID- 22580727
TI  - Hepatic steatosis in type 1 diabetes.
AB  - Islet autoimmunity in type 1 diabetes results in the loss of the pancreatic beta
      cells. The consequences of insulin deficiency in the portal vein for liver fat
      are poorly understood. Under normal conditions, the portal vein provides 75% of
      the liver blood supply. Recent studies suggest that non-alcoholic fatty liver
      disease (NAFLD) may be more common in type 1 diabetes than previously thought,
      and may serve as an independent risk marker for some chronic diabetic
      complications. The pathogenesis of NAFLD remains obscure, but it has been
      hypothesized that hepatic fat accumulation in type 1 diabetes may be due to
      lipoprotein abnormalities, hyperglycemia-induced activation of the transcription
      factors carbohydrate response element-binding protein (ChREBP) and sterol
      regulatory element-binding protein 1c (SREBP-1c), upregulation of glucose
      transporter 2 (GLUT2) with subsequent intrahepatic fat synthesis, or a
      combination of these mechanisms. Novel approaches to non-invasive determinations
      of liver fat may clarify the consequences for liver metabolism when the pancreas
      has ceased producing insulin. This article aims to review the factors potentially
      contributing to hepatic steatosis in type 1 diabetes, and to assess the
      feasibility of using liver fat as a prognostic and/or diagnostic marker for the
      disease. It provides a background and a case for possible future studies in the
      field.

PMID- 22580730
TI  - Normal fasting plasma glucose and risk of prediabetes and type 2 diabetes: the
      Isfahan Diabetes Prevention Study.
AB  - AIM: To determine the association of fasting plasma glucose (FPG) level within
      normal range and the risk of prediabetes and type 2 diabetes in an Iranian
      population. METHODS: A total of 806 first-degree relatives (FDRs) of patients
      with type 2 diabetes who had FPG levels less than 5.6 mmol/l (100 mg/dl) in 2003
      to 2005, and who did not have diabetes or impaired fasting glucose (IFG), were
      followed through 2010 for the occurrence of prediabetes or type 2 diabetes. At
      baseline and through follow-ups, participants underwent a standard 75 g 2-hour
      oral glucose tolerance test (OGTT). RESULTS: The incidence of type 2 diabetes,
      impaired glucose tolerance (IGT), and IFG was 9.6 (95% confidence interval (CI):
      6.8-12.4), 28.7 (23.8-33.6), and 33.0 (27.7-38.2) per 1,000 person-years based on
      4,489 person-years of follow-up, respectively. FPG was associated with the
      incidence of diabetes, IGT, and IFG. The multivariate-adjusted hazard ratios (95%
      CI) for diabetes, IGT, and IFG were 1.36 (1.01-1.84), 1.45 (1.10-1.91) and 1.31
      (1.00-1.71), for the highest quintile of FPG compared with the lowest quintile,
      respectively. CONCLUSIONS: An increase in FPG in the normal range is associated
      with an increase in the incidence of IGT, IFG, and type 2 diabetes. These results
      prove FPG in the normal range to be useful in identifying apparently healthy FDRs
      of patients with type 2 diabetes at risk of developing prediabetes and diabetes.

PMID- 22580731
TI  - Proliferating bloodstream-form Trypanosoma brucei use a negligible part of
      consumed glucose for anabolic processes.
AB  - Our quantitative knowledge of carbon fluxes in the long slender bloodstream form
      (BSF) Trypanosoma brucei is mainly based on non-proliferating parasites, isolated
      from laboratory animals and kept in buffers. In this paper we present a carbon
      balance for exponentially growing bloodstream form trypanosomes. The cells grew
      with a doubling time of 5.3h, contained 46 MU mol of carbon (10(8) cells)(-1) and
      had a glucose consumption flux of 160 nmol min(-1) (10(8) cells)(-1). The molar
      ratio of pyruvate excreted versus glucose consumed was 2.1. Furthermore, analysis
      of the (13)C label distribution in pyruvate in (13)C-glucose incubations of
      exponentially growing trypanosomes showed that glucose was the sole substrate for
      pyruvate production. We conclude that the glucose metabolised in glycolysis was
      hardly, if at all, used for biosynthetic processes. Carbon flux through
      glycolysis in exponentially growing trypanosomes was 10 times higher than the
      incorporation of carbon into biomass. This biosynthetic carbon is derived from
      other precursors present in the nutrient rich growth medium. Furthermore, we
      found that the glycolytic flux was unaltered when the culture went into
      stationary phase, suggesting that most of the ATP produced in glycolysis is used
      for processes other than growth.

PMID- 22580729
TI  - Acute effects of dietary fat on inflammatory markers and gene expression in first
      degree relatives of type 2 diabetes patients.
AB  - BACKGROUND: Subjects with type 2 diabetes (T2D) and their relatives (REL) carry
      an increased risk of cardiovascular disease (CVD). Low-grade inflammation, an
      independent risk factor for CVD, is modifiable by diet. Subjects with T2D show
      elevated postprandial inflammatory responses to fat-rich meals, while information
      on postprandial inflammation in REL is sparse. AIM: To clarify whether medium
      chain saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) have
      differential acute effects on low-grade inflammation in REL compared to controls
      (CON). METHODS: In randomized order, 17 REL and 17 CON ingested two fat-rich
      meals, with 72 energy percent from MUFA and 79 energy percent from mainly medium
      chain SFA, respectively. Plasma high sensitivity C-reactive protein (hs-CRP),
      interleukin-6 (IL-6), adiponectin, and leptin were measured at baseline, 15 min,
      60 min, and 240 min postprandially. Muscle and adipose tissue biopsies were taken
      at baseline and 210 min after the test meal, and expression of selected genes was
      analyzed. RESULTS: Plasma IL-6 increased (p < 0.001) without difference between
      REL and CON and between the meals, whereas plasma adiponectin and plasma hs-CRP
      were unchanged during the 240 min observation period. Plasma leptin decreased
      slightly in response to medium-chain SFA in both groups, and to MUFA in REL.
      Several genes were differentially regulated in muscle and adipose tissue of REL
      and CON. CONCLUSIONS: MUFA and medium-chain SFA elicit similar postprandial
      circulating inflammatory responses in REL and CON. Medium-chain SFA seems more
      proinflammatory than MUFA, judged by the gene expression in muscle and adipose
      tissue of REL and CON.

PMID- 22580732
TI  - Invasion and initial replication of ultraviolet irradiated waterborne infective
      stages of Myxobolus cerebralis results in immunity to whirling disease in rainbow
      trout.
AB  - Myxobolus cerebralis is a microscopic metazoan parasite (Phylum Myxozoa:
      Myxosporea) associated with salmonid whirling disease. There are currently no
      vaccines to minimise the serious negative economical and ecological impacts of
      whirling disease among populations of salmonid fish worldwide. UV irradiation has
      been shown to effectively inactivate the waterborne infective stages or
      triactinomyxons of M. cerbralis in experimental and hatchery settings but the
      mechanisms by which the parasite is compromised are unknown. Treatments of
      triactinomyxons with UV irradiation at doses from 10 to 80 mJ/cm(2) either
      prevented (20-80 mJ/cm(2)) or significantly inhibited (10 mJ/cm(2)) completion of
      the parasite life cycle in experimentally exposed juvenile rainbow trout
      (Oncorhynchus mykiss). However, even the highest doses of UV irradiation examined
      (80 mJ/cm(2)) did not prevent key steps in the initiation of parasite infection,
      including attachment and penetration of the epidermis of juvenile rainbow trout
      as demonstrated by scanning electron and light microscopy. Furthermore,
      replication of UV-treated parasites within the first 24h following invasion of
      the caudal fin was suggested by the detection of concentrations of parasite DNA
      by quantitative PCR comparable to that among fish exposed to an equal
      concentration of untreated triactinomyxons. Subsequent development of parasites
      treated with an 80 mJ/cm(2) dose of UV irradiation however, was impaired as
      demonstrated by the decline and then lack of detection of parasite DNA; a trend
      beginning at 10 days and continuing thereafter until the end of the study at 46
      days post parasite exposure. Treatments of triactinomyxons with a lower dose of
      UV irradiation (20 mJ/cm(2)) resulted in a more prolonged survival with parasite
      DNA detected, although at very low concentrations, in fish up to 49 days post
      parasite exposure. The successful invasion but only short-term survival of
      parasites treated with UV in rainbow trout resulted in a protective response to
      challenges with fully infective triactinomyxons. Prior treatments of juvenile
      rainbow trout with UV-treated triactinomyxons (10 and 20 mJ/cm(2)) resulted in a
      reduced prevalence of infection and significantly lower concentrations of cranial
      myxospores (two direct measures of the severity of whirling disease) compared
      with trout receiving no prior treatments when assessed 5 months post parasite
      exposure to fully infective triactinomyxons.

PMID- 22580734
TI  - Retention of autism spectrum diagnoses by community professionals:  findings from
      the autism and developmental disabilities monitoring network, 2000 and 2006.
AB  - OBJECTIVE: Past research is inconsistent in the stability of autism spectrum
      disorder (ASD) diagnoses. The authors therefore sought to examine the proportion
      of children identified from a population-based surveillance system that had a
      change in classification from ASD to non-ASD and factors associated with such
      changes. METHODS: Children with a documented age of first ASD diagnosis noted in
      surveillance records by a community professional (n = 1392) were identified from
      the Autism and Developmental Disabilities Monitoring Network. Children were
      considered to have a change in classification if an ASD was excluded after the
      age of first recorded ASD diagnosis. Child and surveillance factors were entered
      into a multivariable regression model to determine factors associated with
      diagnostic change. RESULTS: Only 4% of our sample had a change in classification
      from ASD to non-ASD noted in evaluation records. Factors associated with change
      in classification from ASD to non-ASD were timing of first ASD diagnosis at 30
      months or younger, onset other than developmental regression, presence of
      specific developmental delays, and participation in a special needs classroom
      other than autism at 8 years of age. CONCLUSIONS: Our results found that children
      with ASDs are likely to retain an ASD diagnosis, which underscores the need for
      continued services. Children diagnosed at 30 months or younger are more likely to
      experience a change in classification from ASD to non-ASD than children diagnosed
      at 31 months or older, suggesting earlier identification of ASD symptoms may be
      associated with response to intervention efforts or increased likelihood for
      overdiagnosis.

PMID- 22580735
TI  - Breastfeeding and its relation to maternal sensitivity and infant attachment.
AB  - OBJECTIVE: To examine the association of breastfeeding with maternal sensitive
      responsiveness and infant-mother attachment security and disorganization.
      METHODS: We included 675 participants of a prospective cohort study.
      Questionnaires about breastfeeding practices were administered at 2 and 6 months
      postpartum. At 14 months, maternal sensitive responsiveness was assessed in a 13
      minute laboratory procedure using Ainsworth's sensitivity scales, and attachment
      quality was assessed with the Strange Situation Procedure. Mothers were genotyped
      for oxytocin receptor genes OXTR rs53576 and OXTR rs2254298. Linear regressions
      and analyses of covariance adjusted for various background variables were
      conducted. We tested for mediation and moderation by maternal sensitive
      responsiveness and maternal oxytocin receptor genotype. RESULTS: Continuous
      analyses showed that longer duration of breastfeeding was associated with more
      maternal sensitive responsiveness (B = 0.11, 95% confidence interval [CI] 0.02;
      0.20, p < .05), more attachment security (B = 0.24, 95% CI = 0.02; 0.46, p <
      .05), and less attachment disorganization (B = -0.20, 95% CI -0.36; -0.03, p <
      .05). Duration of breastfeeding was not related to the risk of insecure-avoidant
      or insecure-resistant versus secure attachment classification, but longer
      duration of breastfeeding predicted a lower risk of disorganized versus secure
      attachment classification (n = 151; odds ratio [OR] = 0.81, 95% CI 0.66 to 0.99,
      p = .04). Maternal sensitive responsiveness did not mediate the associations, and
      maternal oxytocin receptor genotype was not a significant moderator. CONCLUSIONS:
      Although duration of breastfeeding was not associated with differences in infant
      mother attachment classifications, we found subtle positive associations between
      duration of breastfeeding and sensitive responsiveness, attachment security, and
      disorganization.

PMID- 22580736
TI  - Disclosure of diagnosis:  to tell or not to tell?
AB  - CASE: Jimmy is an 8-year-old boy with hepatitis B, e antigen (HBeAg)-positive,
      HIV and hepatitis C negative, who was adopted from Vietnam when he was 5 years
      and has been followed in your primary care practice since that time. Before
      adoption, he lived in an orphanage, where he was placed soon after birth. Jimmy
      currently lives with his adoptive mother and grandparents. His adoptive father
      has amyotrophic lateral sclerosis and recently moved to a nursing home due to a
      need for more intensive care. Jimmy continues to see him regularly.Jimmy's mother
      presents today upset about a recent encounter with his hepatologist. During this
      visit, Jimmy's doctor was insistent that Jimmy should be told about his illness
      immediately. He felt that Jimmy "had a right to know" and that it was important
      for the protection of other children. Jimmy's family practices universal
      precautions and Jimmy is compliant with these safety measures. Jimmy's mother has
      chosen not to share his diagnosis with the school and in addition has not felt
      the time was right to disclose the diagnosis to Jimmy. He is asymptomatic, takes
      no medications, and is followed yearly by a hepatologist. His mother is concerned
      that Jimmy would have difficulty managing this information and maintaining a
      "secret." However, she also worries that he may feel his trust has been violated
      if she delays telling him.Jimmy is currently 8 years old, in second grade, and is
      struggling academically with math and reading. Socially, he is reported to have
      difficulty making friends and reading social cues. For example, he displays
      inappropriate boundaries, often standing too close or touching others, which has
      resulted in children avoiding him. During your annual visit, Jimmy presented as a
      friendly and engaging boy. He maintained conversation about school and some of
      his interests, but he was often distractible, impulsive, at times grabbing
      things, and fidgety, frequently standing up and then sitting back down. Jimmy's
      mother reports that this behavior is similar to what he exhibits in the
      classroom. He is currently receiving English as a Second Language services and is
      enrolled in a weekly "lunch bunch." What advice would you give the family?

PMID- 22580737
TI  - Mercury concentration in the spectacled caiman and black caiman (Alligatoridae)
      of the Amazon: implications for human health.
AB  - Mercury (Hg) concentrations in the Amazon are generally high, but no studies have
      been published on Hg concentrations in caimans (Alligatoridae) from the region.
      Aiming for sizes representative of caimans traded for food in the Amazon, we
      measured Hg concentration in tail muscle of spectacled caiman (Caiman crocodilus
      crocodilus) and black caiman (Melanosuchus niger) from the Purus River basin. The
      information on Hg concentration in caimans from this area is important because of
      the potential health risk to humans and other animals that eat them as well as
      the potential use of these top-level predators as bioindicators. There were no
      significant interspecific or sex differences in Hg concentrations. The mean Hg
      concentration was 291.2 MUg/kg in C. c. crocodilus and 193.9 MUg/kg in M. niger.
      A significant positive correlation between Hg concentration and size was found
      for M. niger (p = 0.005) but not for C. c. crocodilus. Our Hg sample from M.
      niger corresponded to the size of M. niger collected for commercial trade, but
      our Hg sample from C. c. crocodilus turned out to be significantly smaller than
      the trade samples (p = 0.004), but this difference is not pertinent in the
      absence of a correlation between size and Hg concentration for this species.
      Although there are no standards for reptile meat, both species had mean Hg
      concentrations lower than the maximum allowable level of 500 MUg/kg Hg
      recommended by the World Health Organization and by the Brazilian Health Ministry
      for fish. However, by calculating daily consumptions limits and number of meals
      per month that can be safely consumed, we found that consumers who eat caimans
      frequently may be at risk for Hg-related health problems.

PMID- 22580738
TI  - Enhancement of cellular uptake and cytotoxicity of curcumin-loaded PLGA
      nanoparticles by conjugation with anti-P-glycoprotein in drug resistance cancer
      cells.
AB  - AIM: To compare the anti-cancer activity and cellular uptake of curcumin (Cur)
      delivered by targeted and non-targeted drug delivery systems in multidrug
      resistant cervical cancer cells. METHODS: Cur was entrapped into poly (DL-lactide
      co-glycolide) (PLGA) nanoparticles (Cur-NPs) in the presence of modified-pluronic
      F127 stabilizer using nano-precipitation technique. On the surface of Cur-NPs,
      the carboxy-terminal of modified pluronic F127 was conjugated to the amino
      terminal of anti-P-glycoprotein (P-gp) (Cur-NPs-APgp). The physical properties of
      the Cur-NPs, including particle size, zeta potential, particle morphology and Cur
      release kinetics, were investigated. Cellular uptake and specificity of the Cur
      NPs and Cur-NPs-APgp were detected in cervical cancer cell lines KB-V1 (higher
      expression of P-gp) and KB-3-1 (lower expression of P-gp) using fluorescence
      microscope and flow cytometry, respectively. Cytotoxicity of the Cur-NPs and Cur
      NPs-APgp was determined using MTT assay. RESULTS: The particle size of Cur-NPs
      and Cur-NPs-APgp was 127 and 132 nm, respectively. The entrapment efficiency and
      actual loading of Cur-NPs-APgp (60% and 5 MUg Cur/mg NP) were lower than those of
      Cur-NPs (99% and 7 MUg Cur/mg NP). The specific binding of Cur-NPs-APgp to KB-V1
      cells was significantly higher than that to KB-3-1 cells. Cellular uptake of Cur
      NPs-APgp into KB-V1 cells was higher, as compared to KB-3-1 cells. However, the
      cellular uptake of Cur-NPs and Cur-NPs-IgG did not differ between the two types
      of cells. Besides, the cytotoxicity of Cur-NPs-APgp in KB-V1 cells was higher
      than those of Cur and Cur-NPs. CONCLUSION: The results demonstrate that Cur-NPs
      APgp targeted to P-gp on the cell surface membrane of KB-V1 cells, thus enhancing
      the cellular uptake and cytotoxicity of Cur.

PMID- 22580739
TI  - Combined administration of anisodamine and neostigmine produces anti-shock
      effects: involvement of alpha7 nicotinic acetylcholine receptors.
AB  - AIM: To evaluate the anti-effects of anisodamine and neostigmine in animal models
      of endotoxic and hemorrhagic shock. METHODS: Kunming mice were injected with
      lipopolysaccharide (LPS 30 mg/kg, ip) to induce endotoxic shock. Anisodamine
      (12.5, 25, and 50 mg/kg, ip) and neostigmine (12.5, 25, and 50 MUg/kg, ip) were
      administered immediately after LPS injection. Survival rate was monitored, and
      the serum levels of TNF-alpha and IL-1beta were analyzed using ELISA assays. The
      effects of anisodamine and neostigmine were also examined in alpha7 nicotinic
      acetylcholine receptor (alpha7 nAChR) knockout mice with endotoxic shock and in
      Beagle dogs with hemorrhagic shock. RESULTS: In mice with experimental
      endotoxemia, combined administration of anisodamine and neostigmine significantly
      increased the survival rate and decreased the serum levels of inflammatory
      cytokines, as compared to those produced by either drug alone. The anti-shock
      effect of combined anisodamine and neostigmine was abolished in alpha7 nAChR
      knockout mice. On the other hand, intravenous injection of the combined
      anisodamine and neostigmine, or the selective alpha7 nAChR agonist PNU282987
      exerted similar anti-shock effects in dogs with hemorrhagic shock. CONCLUSION:
      The results demonstrate that combined administration of anisodamine and
      neostigmine produces significant anti-shock effects, which involves activation of
      alpha7 nAChRs.

PMID- 22580740
TI  - Pirarubicin inhibits multidrug-resistant osteosarcoma cell proliferation through
      induction of G2/M phase cell cycle arrest.
AB  - AIM: Pirarubicin (THP) is recently found to be effective in treating patients
      with advanced, relapsed or recurrent high-grade osteosarcoma. In this study, the
      effects of THP on the multidrug-resistant (MDR) osteosarcoma cells were assessed,
      and the underlying mechanisms for the disruption of cell cycle kinetics by THP
      were explored. METHODS: Human osteosarcoma cell line MG63 and human MDR
      osteosarcoma cell line MG63/DOX were tested. The cytotoxicity of drugs was
      examined using a cell proliferation assay with the Cell Counting Kit-8 (CCK-8).
      The distribution of cells across the cell cycle was determined with flow
      cytometry. The expression of cell cycle-regulated genes cyclin B1 and Cdc2
      (CDK1), and the phosphorylated Cdc2 and Cdc25C was examined using Western blot
      analyses. RESULTS: MG63/DOX cells were highly resistant to doxorubicin (ADM) and
      gemcitabine (GEM), but were sensitive or lowly resistant to THP, methotrexate
      (MTX) and cisplatin (DDP). Treatment of MG63/DOX cells with THP (200-1000 ng/mL)
      inhibited the cell proliferation in time- and concentration-dependent manners.
      THP (50-500 ng/mL) induced MG63/DOX cell cycle arrest at the G(2)/M phase in time
      and concentration-dependent manners. Furthermore, the treatment of MG63/DOX
      cells with THP (200-1000 ng/mL) downregulated cyclin B1 expression, and decreased
      the phosphorylated Cdc2 at Thr(161). Conversely, the treatment increased the
      phosphorylated Cdc2 at Thr(14)/Tyr(15) and Cdc25C at Ser(216), which led to a
      decrease in Cdc2-cyclin B1 activity. CONCLUSION: The cytotoxicity of THP to
      MG63/DOX cells may be in part due to its ability to arrest cell cycle progression
      at the G(2)/M phase, which supports the use of THP for managing patients with MDR
      osteosarcoma.

PMID- 22580741
TI  - Urate in Parkinson's disease: more than a biomarker?
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disease with
      characteristic motor manifestations. Although appreciation of PD as a multisystem
      disorder has grown, loss of dopaminergic neurons in the substantia nigra remains
      a pathological and neurochemical hallmark, accounting for the substantial
      symptomatic benefits of dopamine replacement therapies. However, currently no
      treatment has been shown to prevent or forestall the progression of the disease
      in spite of tremendous efforts. Among multiple environmental and genetic factors
      that have been implicated in the pathogenesis of PD, oxidative stress is proposed
      to play a critical role. A recent confluence of clinical, epidemiological, and
      laboratory evidence identified urate, an antioxidant and end product of purine
      metabolism, as not only a molecular predictor for both reduced risk and favorable
      progression of PD but also a potential neuroprotectant for the treatment of PD.
      This review summarizes recent findings on urate in PD and their clinical
      implications.

PMID- 22580743
TI  - Establishment of a canine model of human type 2 diabetes mellitus by
      overexpressing phosphoenolypyruvate carboxykinase.
AB  - Dogs are useful models for studying human metabolic diseases such as type 2
      diabetes mellitus due to similarities in physiology, anatomy and life styles with
      humans. Somatic cell nuclear transfer (SCNT) facilitates the production of
      transgenic dogs. In this study, we generated transgenic dogs expressing the
      phosphoenolpyruvate carboxykinase (PEPCK) gene, which is closely involved in the
      pathogenesis of type 2 diabetes mellitus. In addition, we assessed the cloning
      efficiency associated with adult or fetal (cloned or natural mating) fibroblasts
      as a nuclear source. Cloning efficiency was determined by the fusion, pregnancy
      and cloning rates. The fusion rates were significantly high for fibroblasts from
      cloned fetuses, but the pregnancy and cloning rates were relatively high for
      cells from normal fetuses. Based on these data, fetal fibroblasts were selected
      as the nuclear donor for SCNT and genetically engineered to overexpress the PEPCK
      gene and dual selection marker genes controlled by the PEPCK promoter. The
      transgenic cells were introduced into oocytes and transferred into five recipient
      dogs, resulting in two pregnancies. Finally, three puppies were born and
      confirmed by microsatellite analysis to be genetically identical to the donor.
      One puppy successfully overexpressed PEPCK mRNA and protein in the liver. This
      canine disease model may be useful for studying the pathogenesis and/or
      therapeutic targets of type 2 diabetes mellitus.

PMID- 22580744
TI  - Improving the efficiency of enzyme utilization for sugar beet pulp hydrolysis.
AB  - Sugar beet pulp (SBP) is a carbohydrate-rich residue of table sugar processing.
      It shows promise as a feedstock for fermentable sugar and biofuel production via
      enzymatic hydrolysis and microbial fermentation. This research focused on the
      enzymatic hydrolysis of SBP and examined the effects of solid loading (2-10 %,
      dry basis), enzyme preparation, and enzyme recycle on the production of
      fermentable sugars. The enzyme partitioning to the solid and liquid phases during
      SBP enzymatic hydrolysis and loss during recycling were investigated using SDS
      PAGE and Zymogram analysis. Without considering product inhibition, the cellulase
      added initially to the SBP hydrolysis lost only 6 % filter paper activity and
      negligible carboxymethyl cellulose activity upon multiple cycles of SBP
      hydrolysis. It was found that enzyme dosage can be reduced by 50 % while
      maintaining similar, and in some cases higher fermentable sugar yield. The
      removal of hydrolysis products will further improve enzymatic hydrolysis of SBP
      for biofuel production.

PMID- 22580742
TI  - Neuroinflammation and non-motor symptoms: the dark passenger of Parkinson's
      disease?
AB  - Generally speaking, inflammation as a key piece to the Parkinson's disease (PD)
      puzzle is a relatively new concept. Acceptance of this concept has gained ground
      as studies by various researchers have demonstrated the potential of mitigating
      nigral cell death by curtailing inflammation in animal models of PD. We propose
      that the significance of inflammation in PD pathology may extend beyond the
      nigrostriatal region. In the current review, we present an argument for this
      based on the Braak staging and discuss how inflammation might contribute to the
      development of non-motor PD symptoms.

PMID- 22580745
TI  - Azadirachtin production by hairy root cultivation of Azadirachta indica in a
      modified stirred tank reactor.
AB  - Present investigation involves hairy root cultivation of Azadirachta indica in a
      modified stirred tank reactor under optimized culture conditions for maximum
      volumetric productivity of azadirachtin. The selected hairy root line (Az-35) was
      induced via Agrobacterium rhizogenes LBA 920-mediated transformation of A. indica
      leaf explants (Coimbatore variety, India). Liquid culture of the hairy roots was
      developed in a modified Murashige and Skoog medium (MM2). To further enhance the
      productivity of azadirachtin, selected growth regulators (1.0 mg/l IAA and 0.025
      mg/l GA(3)), permeabilizing agent (0.5 % v/v DNBP), a biotic elicitor (1 % v/v
      Curvularia (culture filtrate)) and an indirectly linked biosynthetic precursor
      (50 mg/l cholesterol) were added in the growth medium on 15th day of the hairy
      root cultivation period in shake flask. Highest azadirachtin production (113
      mg/l) was obtained on 25th day of the growth cycle with a biomass of 21 g/l DW.
      Further, batch cultivation of hairy roots was carried out in a novel liquid-phase
      bioreactor configuration (modified stirred tank reactor with polyurethane foam as
      root support) to investigate the possible scale-up of the established A. indica
      hairy root culture. A biomass production of 15.2 g/l with azadirachtin
      accumulation in the hairy roots of 6.4 mg/g (97.28 mg/l) could be achieved after
      25 days of the batch cultivation period, which was ~27 and ~14 % less biomass and
      azadirachtin concentration obtained respectively, in shake flasks. An overall
      volumetric productivity of 3.89 mg/(l day) of azadirachtin was obtained in the
      bioreactor.

PMID- 22580746
TI  - Calibration and validation of a regionally and seasonally stratified
      macroinvertebrate index for West Virginia wadeable streams.
AB  - Multimetric indices (MMIs) are routinely used by federal, state, and tribal
      entities to assess the quality of aquatic resources. Because of their diversity,
      abundance, ubiquity, and sensitivity to environmental stress, benthic
      macroinvertebrates are well suited for MMIs. West Virginia has used a statewide
      family-level stream condition index (WVSCI) since 2002. We describe the
      development, validation, and application of a geographically- and seasonally
      partitioned genus-level index of most probable stream status (GLIMPSS) for West
      Virginia wadeable streams. Natural classification strata were evaluated with
      reference site communities using mean similarity analysis and non-metric
      multidimensional scaling ordination. Forty-one metrics spanning six ecological
      categories (richness, composition, tolerance, dominance, trophic groups, and
      habits) were evaluated for sensitivity, responsiveness, redundancy, range and
      variability across seasonal (spring and summer) and regional (mountains and
      plateau) strata. Through a step-wise metric selection process, 8-10 metrics were
      aggregated to comprise four stratum-specific GLIMPSS models (mountain/plateau and
      spring/summer). A comparison of GLIMPSS with WVSCI exhibited marked improvements
      where GLIMPSS detecting greater stream impacts. A variation of the GLIMPSS, which
      differs only in the family-level taxonomic identification of Chironomidae
      (GLIMPSS (CF)), was comparable to the full GLIMPSS. These MMIs are robust yet
      practical tools for evaluating impacts to water quality, instream and riparian
      habitat, and aquatic wildlife in wadeable riffle-run streams based on
      sensitivity, responsiveness, precision, and independent validation. These models
      may be used effectively to detect degradation of the naturally occurring benthic
      community, assess causes of biological degradation, and plan and evaluate
      remediation of damaged stream ecosystems.

PMID- 22580747
TI  - Screening for Stockholm Convention persistent organic pollutants in the Bosna
      River (Bosnia and Herzogovina).
AB  - The Stockholm Convention, which aspires to manage persistent organic pollutants
      (POPs) at the international level, was recently ratified in Bosnia and
      Herzegovina (BiH). Despite this fact, there is in general a paucity of data
      regarding the levels of POPs in the environment in BiH. In the present study,
      screening for POPs was conducted in one of the country's major rivers, the Bosna.
      A two-pronged approach was applied using passive samplers to detect the freely
      dissolved and bioavailable concentrations in the water phase and sediment
      analysis to provide an integrated measure of historical contamination. At several
      places along the river, the concentrations of polycyclic aromatic hydrocarbons
      (PAH) were high and exhibited potential for both chronic and acute effects to
      biota. River water also showed elevated concentrations of PAH, up to 480 ng L(-1)
      near the city of Doboj, and diagnostic ratios suggested combustion sources for
      the contamination present in both types of sample. The levels of the other
      contaminants measured-polychlorinated biphenyls (PCBs), organochlorine pesticides
      (OCPs) and polybrominated diphenyl ethers--were generally low in the water phase.
      However, PCBs and some OCPs were present in river sediments at levels which
      breach the international criteria and thus suggest potential for ecological
      damage. Additionally, the levels of heptachlor breached these criteria in many of
      the sites investigated. This study presents the first screening data for some of
      these Stockholm Convention relevant compounds in BiH and reveals both low
      concentrations of some chemical groups, but significant point sources and
      historic contamination for others.

PMID- 22580748
TI  - Distributions, sources, and ecological risks of DDT-related contaminants in
      water, suspended particulate matter, and sediments from Haihe Plain, Northern
      China.
AB  - The residual levels of dichlorodiphenyltrichloroethane (DDT) and its metabolites
      (DDXs, including p,p'-DDT, DDD, and DDE) in water, suspended particulate matter
      (SPM), and sediments from major rivers, lakes, and reservoirs in Haihe Plain were
      measured with a gas chromatograph equipped with a (63)Ni microelectron capture
      detector. In the fall of 2004, the contents of the total DDXs in the water and
      SPM were 0.29 +/- 0.69 ng L(-1) and 423.13 +/- 577.85 ng g(-1) dry wt.,
      respectively. In the spring of 2005, the total DDXs were 0.36 +/- 0.91 ng L(-1)
      for water and 35.93 +/- 62.65 ng g(-1) dry wt. for SPM. The average concentration
      of DDXs for sediments was 7.10 +/- 7.57 ng g(-1) dry wt. during the two seasons.
      The Eastern-Hebei-Province Coastland River System was the most polluted, which
      was mainly attributable to the extensive use of DDT pesticide and dicofol in that
      system. Recent DDT inputs still occur in some regions, as indicated by DDT/(DDD +
      DDE) > 1 at 29-36 % of the sites for water and 55-61 % of the sites for SPM. The
      potential ecological risks of DDT in the water were assessed using a species
      sensitivity distribution model. Only shrimp and crabs were found to have
      potentially affected fraction values of 1.63 * 10(-3) to 2.27 * 10(-4), with
      probabilities beyond the hazardous concentration for 5 % of species (HC5) values
      of 1.90-2.56 %, suggesting only slight risks. DDXs in the sediments of some sites
      were also of potential risk to benthic organism based on consensus-based sediment
      quality guidelines.

PMID- 22580749
TI  - The effects of meteorological parameters in ambient noise modelling studies in
      Delhi.
AB  - The acoustic environment in urban areas has gained prominence in recent times due
      to rapid industrial and commercial development in metropolitan cities. Various
      attempts have been made to predict and model the trends in urban ambient noise
      levels using different statistical and dynamic models. The present study makes an
      attempt to examine the role of meteorological parameters affecting the ambient
      noise levels in Delhi. The results show significant improvement in overall noise
      scenario of Delhi since the introduction of compressed natural gas vehicles in
      public transport of Delhi. The noise level is significantly reduced by high
      vegetation cover as well as by low relative humidity over Delhi. The regression
      models developed for the present study clearly show the significant contribution
      of meteorological parameters in governing the ambient noise levels in Delhi.

PMID- 22580750
TI  - Effects of aging and methionine restriction applied at old age on ROS generation
      and oxidative damage in rat liver mitochondria.
AB  - It is known that a global decrease in food ingestion (dietary restriction, DR)
      lowers mitochondrial ROS generation (mitROS) and oxidative stress in young
      immature rats. This seems to be caused by the decreased methionine ingestion of
      DR animals. This is interesting since isocaloric methionine restriction in the
      diet (MetR) also increases, like DR, rodent maximum longevity. However, it is not
      known if old rats maintain the capacity to lower mitROS generation and oxidative
      stress in response to MetR similarly to young immature animals, and whether MetR
      implemented at old age can reverse aging-related variations in oxidative stress.
      In this investigation the effects of aging and 7 weeks of MetR were investigated
      in liver mitochondria of Wistar rats. MetR implemented at old age decreased
      mitROS generation, percent free radical leak at the respiratory chain and mtDNA
      oxidative damage without changing oxygen consumption. Protein oxidation,
      lipoxidation and glycoxidation increased with age, and MetR in old rats partially
      or totally reversed these age-related increases. Aging increased the amount of
      SIRT1, and MetR decreased SIRT1 and TFAM and increased complex IV. No changes
      were observed in the protein amounts of PGC1, Nrf2, MnSOD, AIF, complexes I, II
      and III, and in the extent of genomic DNA methylation. In conclusion, treating
      old rats with isocaloric short-term MetR lowers mitROS production and free
      radical leak and oxidative damage to mtDNA, and reverses aging-related increases
      in protein modification. Aged rats maintain the capacity to lower mitochondrial
      ROS generation and oxidative stress in response to a short-term exposure to
      restriction of a single dietary substance: methionine.

PMID- 22580751
TI  - Over-expression of RPL23 in myelodysplastic syndromes is associated with
      apoptosis resistance of CD34+ cells and predicts poor prognosis and distinct
      response to CHG chemotherapy or decitabine.
AB  - Ribosomal protein (RP) L23 has been suggested to be a negative regulator of cell
      apoptosis. In the present study, we analyzed RPL23 expression in 169 patients
      with myelodysplastic syndrome (MDS) by using real-time PCR. The apoptosis of
      CD34(+) marrow cells was examined by flow cytometry, and the correlation between
      RPL23 expression levels and apoptosis in CD34(+) cells was assessed. We then
      analyzed the clinical significance of RPL23 expression for predicting disease
      progression and patient survival as well as therapeutic response in patients
      administered with a cytarabine, homoharringtonine, and G-CSF (CHG) regimen or
      decitabine therapy. Increased RPL23 expression was found in patients with higher
      risk MDS than in patients with lower-risk disease (p = 0.004). RPL23 expression
      levels were found being inversely correlated with decreased apoptotic ratio of
      CD34(+) cells in higher-risk patients (r = -0.672, p < 0.001). Compared to
      patients with normal RPL23 expression levels, those with increased RPL23
      expression presented higher rates of transformation to acute myeloid leukemia (p
      = 0.005) and reduced 2-year survival rates (p = 0.012). Multivariate regression
      analysis showed that RPL23 expression level was an independent predictor of
      prognosis, regardless of patient age, IPSS score, or hemoglobin level. Moreover,
      patients with RPL23 over-expression appeared to have lower response rates to CHG
      chemotherapy (p = 0.027) but similar response rates to decitabine treatment. In
      conclusion, the over-expression of RPL23 might confer apoptosis resistance in
      CD34(+) cells, which may lead to disease progression and adverse prognosis in
      MDS. Increased RPL23 expression was an inverse indicator for CHG regimen, but not
      for decitabine treatment.

PMID- 22580752
TI  - Postfunctionalization of periodic mesoporous silica SBA-1 with magnesium(II) and
      iron(II) silylamides.
AB  - Magnesium silylamide complexes Mg[N(SiHMe(2))(2)](2)(THF)(2) and
      Mg[N(SiPhMe(2))(2)](2) were synthesized according to transsilylamination and
      alkane elimination protocols, respectively, utilizing
      Mg[N(SiMe(3))(2)](2)(THF)(2) and [Mg(n-Bu)](2) as precursors. Cage-like periodic
      mesoporous silica SBA-1 was treated with donor solvent-free dimeric
      [Mg{N(SiHMe(2))(2)}(2)](2), [Mg{N(SiMe(3))(2)}(2)](2) and monomeric
      Mg[N(SiPhMe(2))(2)](2), producing hybrid materials [Mg(NR(2))(2)]@SBA-1 with
      magnesium located mainly at the external surface. Consecutive grafting of
      [Mg{N(SiHMe(2))(2)}(2)](2) and [Fe(II){N(SiHMe(2))(2)}(2)](2) onto SBA-1 led to
      heterobimetallic hybrid materials which exhibit complete consumption of the
      isolated surface silanol groups, evidencing intra-cage surface functionalization.
      All materials were characterized by DRIFT spectroscopy, nitrogen physisorption
      and elemental analysis.

PMID- 22580753
TI  - New kind of polarotaxis governed by degree of polarization: attraction of tabanid
      flies to differently polarizing host animals and water surfaces.
AB  - Aquatic insects find their habitat from a remote distance by means of horizontal
      polarization of light reflected from the water surface. This kind of positive
      polarotaxis is governed by the horizontal direction of polarization (E-vector).
      Tabanid flies also detect water by this kind of polarotaxis. The host choice of
      blood-sucking female tabanids is partly governed by the linear polarization of
      light reflected from the host's coat. Since the coat-reflected light is not
      always horizontally polarized, host finding by female tabanids may be different
      from the established horizontal E-vector polarotaxis. To reveal the optical cue
      of the former polarotaxis, we performed choice experiments in the field with
      tabanid flies using aerial and ground-based visual targets with different degrees
      and directions of polarization. We observed a new kind of polarotaxis being
      governed by the degree of polarization rather than the E-vector direction of
      reflected light. We show here that female and male tabanids use polarotaxis
      governed by the horizontal E-vector to find water, while polarotaxis based on the
      degree of polarization serves host finding by female tabanids. As a practical by
      product of our studies, we explain the enigmatic attractiveness of shiny black
      spheres used in canopy traps to catch tabanids.

PMID- 22580754
TI  - Preparation and characterization of nanoparticles based on histidine-hyaluronic
      acid conjugates as doxorubicin carriers.
AB  - Histidine-hyaluronic acid (His-HA) conjugates were synthesized using hyaluronic
      acid (HA) as a hydrophilic segment and histidine (His) as hydrophobic segment by
      1-ethyl-3(3-dimethylaminopropyl)carbodiimide (EDC) mediated coupling reactions.
      The structural characteristics of the His-HA conjugates were investigated using
      (1)H NMR. His-HA nanoparticles (HH-NPs) were prepared based on His-HA conjugates,
      and the characteristics of HH-NPs were investigated using dynamic light
      scattering, transmission electron microscopy (TEM), scanning electron microscopy
      (SEM), and fluorescence spectroscopy. The particles were between 342 and 732 nm
      in size, depending on the degree of substitution (DS) of the His. TEM and SEM
      images indicated that the morphology of HH-NPs was spherical in shape. The
      critical aggregation concentrations of HH-NPs ranged from 0.034 to 0.125 mg/ml,
      which decreased with an increase in the DS of the His. Images of fluorescence
      microscopy indicate that HH-NPs were taken up by the cancer cell line (MCF-7),
      and significantly decreased by competition inhibition of free HA. From the
      cytotoxicity test, it was found that DOX-loaded HH-NPs exhibited similar dose and
      time-dependent cytotoxicity against MCF-7 cells with free DOX.

PMID- 22580755
TI  - Sol-gel derived 45S5 bioglass: synthesis, microstructural evolution and thermal
      behaviour.
AB  - In this work, the 45S5 bioactive glass was synthesized through an aqueous sol-gel
      method. Characteristic functional groups were evidenced by Fourier transform
      infrared spectroscopy, the thermal behaviour was investigated by
      thermogravimetric and differential thermal analysis, crystallization kinetics and
      phase evolution were followed by X-ray diffraction measurements. The sintering
      behaviour of the sol-gel derived 45S5 was then studied by dilatometry and the
      microstructural evolution was followed step-by-step, interrupting the thermal
      cycle at different temperatures. In vitro dissolution tests were performed in
      order to assess the degradation behaviour of sol-gel derived 45S5 samples
      thermally treated at different temperatures. A relevant influence of the
      calcination conditions (namely, dwelling time and temperature) of the as-prepared
      powder on the phase appearance and its sintering behaviour as well as on the
      porosity features, in terms of pore dimension and interconnectivity, of the fired
      materials was stated.

PMID- 22580756
TI  - Significance of molecular identification and antifungal susceptibility of
      clinically significant yeasts and moulds in a global antifungal surveillance
      programme.
AB  - The increasing diversity of opportunistic fungi causing serious invasive fungal
      infections (IFI) has been documented. Accurate identification (ID) is important
      in guiding therapy, determining prognosis for IFIs and in epidemiological
      surveys. We assessed the utility of PCR-based methods for the ID of yeasts and
      moulds that either were uncommon, failed conventional ID, or represented unusual
      biochemical or phenotypic profiles of common species. Among 1,790 viable fungal
      clinical isolates received during the SENTRY Program in 2010, 322 strains from 40
      study sites had ID confirmed by molecular methods. Isolates were previously
      identified in participant institutions. Yeasts that were not confirmed by
      morphology on CHROMagar, growth at 45  degrees C (Candida albicans/dubliniensis),
      or assimilation of trehalose (C. glabrata) as well as non-Candida yeasts and all
      moulds were amplified and sequenced using primers amplifying one or more of the
      following genes: ITS, 28S, beta-tubulin (Aspergillus spp.), TEF (Fusarium spp.),
      IGS (Trichosporon spp.). The isolates selected for molecular ID included 149
      isolates of Candida species, 77 of Aspergillus species, 73 non-Candida yeasts,
      and 23 other moulds (a total of 41 different species). Overall, the ID determined
      by the submitting site was confirmed for 189 isolates (58.7 %): Aspergillus spp.
      (64.1 % correct); Candida spp. (60.1 % correct); non-Candida yeasts (58.9 %
      correct); non-Aspergillus moulds (30.4 % correct). Species with high levels of
      concordance between conventional and molecular ID included A. fumigatus (95.0 
      %), C. lusitaniae (100 %), C. dubliniensis (92.3 %), C. kefyr (100 %), and C.
      neoformans (90.2 %). Only 50.0 % of isolates of C. albicans and 59.1 % of C.
      glabrata selected due to unusual phenotypic or biochemical features were found to
      be correctly identified by the submitting site. Molecular methods for the
      identification of fungal pathogens are an important adjunct to the conventional
      identification of many less common clinically relevant yeasts and moulds
      including species of Candida with unusual or erroneous phenotypic or biochemical
      profiles. Molecular confirmation of fungal identification is essential in
      epidemiological surveys such as SENTRY.

PMID- 22580758
TI  - Differential effects of mechanical strain on osteoclastogenesis and osteoclast
      related gene expression in RAW264.7 cells.
AB  - Mechanical strain plays a critical role in the formation, proliferation and
      maturation of bone cells. However, little is known about the direct effects of
      different magnitudes of mechanical strain on osteoclast differentiation. The aim
      of the present study was to investigate how the fusion and activation of
      osteoclasts can be regulated by mechanical strain magnitude using the RAW264.7
      mouse monocyte/macrophage cell line as an osteoclast precursor. Mechanical strain
      (substrate stretching) was applied via a 4-point bending system when RAW cells
      were treated with macrophage colony-stimulating factor (M-CSF) and receptor
      activator of nuclear factor-kappaB (RANK) ligand (RANKL) for an indicated period
      of time. The numbers of tartrate-resistant acid phosphatase-positive (TRAP+) and
      apoptotic cells were counted. The expression of TRAP, matrix metalloproteinase-9
      (MMP-9), RANK, cathepsin K and carbonic anhydrase II (CAII) was measured by semi
      quantitative RT-PCR, and immunocytochemistry staining for RANK was performed. We
      found that the number of nuclei per osteoclast derived from RAW cells decreased
      under low magnitude mechanical strain and increased under high magnitude strain
      within physiological load with an enhanced fusion of TRAP+ osteoclasts, compared
      to the control with no mechanical strain. The expression of RANK mRNA was
      downregulated by low magnitude strain and beyond physiological load, while it was
      upregulated by high magnitude strain within physiological load, correlating with
      the increased expression of RANK examined by immunocytochemistry, suggesting the
      mechanical regulation of RANK expression. There was also an increase in the
      expression of MMP-9 mRNA in the groups subjected to a mechanical strain of 2,000
      and 2,500 uepsilon. No significant differences were detected in the expression of
      TRAP mRNA, cathepsin K and CAII under mechanical strain compared to the control
      under no strain (0 uepsilon). These findings indicate that low-magnitude strain
      suppresses osteoclast fusion and activation, while high-magnitude strain within
      physiological load promotes osteoclast fusion and activation related to a
      mechanical magnitude-dependent response of RANK expression. These data,
      therefore, provide a deeper understanding of how different magnitudes of
      mechanical strains exert their effects on osteoclastogenesis.

PMID- 22580757
TI  - Impact of prenatal immune system disturbances on brain development.
AB  - As research into various aging-associated neurodegenerative disorders reveals
      their immense pathophysiological complexity, the focus is currently shifting from
      studying changes in an advanced disease state to investigations involving pre
      symptomatic periods, possible aberrations in early life, and even abnormalities
      in brain development. Recent studies on the etiology of schizophrenia and autism
      spectrum disorders revealed a profound impact of neurodevelopmental disturbances
      on disease predisposition, onset and progression. Here, we discuss how a prenatal
      immune challenge can affect the developing brain-with a selective focus on the
      impact on microglia, the brain's immune cells-and the implications for brain
      aging and its associated risk of developing Alzheimer's disease.

PMID- 22580759
TI  - Prediction of tolerance in children with IgE mediated cow's milk allergy by
      microarray profiling and chemometric approach.
AB  - The sera of a retrospective cohort (n=41) composed of children with well
      characterized cow's milk allergy collected from multiple visits were analyzed
      using a protein microarray system measuring four classes of immunoglobulins. The
      frequency of the visits, age and gender distribution reflected real situation
      faced by the clinicians at a pediatric reference center for food allergy in Sao
      Paulo, Brazil. The profiling array results have shown that total IgG and IgA
      share similar specificity whilst IgM and in particular IgE are distantly related.
      The correlation of specificity of IgE and IgA is variable amongst the patients
      and this relationship cannot be used to predict atopy or the onset of tolerance
      to milk. The array profiling technique has corroborated the clinical selection
      criteria for this cohort albeit it clearly suggested that 4 out of the 41
      patients might have allergies other than milk origin. There was also a good
      correlation between the array data and ImmunoCAP results, casein in particular.
      By using qualitative and quantitative multivariate analysis routines it was
      possible to produce validated statistical models to predict with reasonable
      accuracy the onset of tolerance to milk proteins. If expanded to larger study
      groups, the array profiling in combination with the multivariate techniques show
      potential to improve the prognostic of milk allergic patients.

PMID- 22580760
TI  - Autoantibodies directed against labile epitopes on cell surface proteins in
      autoimmune disease patients: proposal of a novel ELISA for the detection of anti
      endothelial cell antibodies.
AB  - This article describes a novel method for detecting anti-endothelial cell
      antibodies (AECAs). Sera from patients with systemic vasculitis or inflammatory
      conditions have been reported to contain antibodies (Abs) that bind to
      endothelial cells (EC), i.e., AECAs. AECAs are known to play immunogenic effects
      by triggering EC activation and vascular damage, but the immunopathological role
      of AECAs is not clear. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE) and Western blotting have previously been used for detecting target
      antigens of AECAs. However, we assumed that these methods are not appropriate for
      searching genuine target antigens (Ags) on cell surface, and developed a novel
      solubilized cell surface protein-capture ELISA (CSP-ELISA). Ags were obtained as
      cell surface proteins from the plasma membrane of human umbilical vein
      endothelial cells (HUVECs); these cell surface proteins were biotinylated,
      solubilized with detergent, and captured on ELISA wells coated with NeutrAvidinTM
      biotin binding protein (NeuAvi). AECA titers in serum from 126 autoimmune disease
      patients and 122 healthy donors were tested. AECAs were detected in 28 of 36
      (78%) of systemic lupus erythematosus (SLE) patients; in 13 of 16 (81%) of mixed
      connective tissue disease (MCTD) patients; and in 5 of 9 (56%) of systemic
      sclerosis (SSc) patients. Relatively weak denaturation of antigens on ELISA wells
      caused loss of binding of these autoantibodies (autoAbs). Thus, this newly
      developed CSP-ELISA method enables the detection of Abs to the labile epitopes of
      autoantigens (autoAgs) such as membrane proteins, and this method is generally
      applicable to various kinds of membrane proteins and the Abs against them. We
      propose CSP-ELISA for measuring AECAs in serum samples for routine laboratory
      testing.

PMID- 22580761
TI  - Serum LBP levels reflect the impaired synthetic capacity of the remnant liver
      after partial hepatectomy in rats.
AB  - Lipopolysaccharide (LPS) binding protein (LBP) is up-regulated in inflammation
      and infection. Its use as a biomarker of severe infection and sepsis is currently
      discussed controversially. Here a novel LBP-ELISA was established to assess serum
      LBP-levels after various degree of in a rat partial hepatectomy (PH) model. The
      LBP enzyme-linked immunosorbent assay (ELISA) was designed based on the binding
      between LPS and LBP. LPS was employed as capture molecule. An anti-LBP antibody
      was used as detection antibody. Serum LBP levels were measured in serum obtained
      24h after 30% PH, 70% PH and 90% PH in rats using newly established LBP ELISA
      method. Expression of hepatic LBP mRNA was measured by real-time quantitative
      reverse transcription polymerase chain reaction (RT-PCR). The detection range of
      the ELISA was from 0.1 MUg/ml to 60 MUg/ml. The correlation between ELISA and
      western blotting was strong (r=0.885, p<0.0001). Hepatic LBP mRNA expression was
      upregulated after PH. Of note, elevations of serum LBP protein levels were
      positively correlated to the remnant liver mass (R=0.821, p<0.0001), serum
      albumin levels (R=0.532, p<0.05) and total protein levels(R=0.813, p<0.0001). In
      conclusion, we established an economic and rapid ELISA assay for rat serum LBP
      quantification. Our results speak against using LBP as diagnostic marker of the
      acute phase response after liver resection as its elevation is related to the
      size and thereby the synthetic capacity of the small remnant liver.

PMID- 22580762
TI  - Towards a xeno-free and fully chemically defined cryopreservation medium for
      maintaining viability, recovery, and antigen-specific functionality of PBMC
      during long-term storage.
AB  - Analysis of cryopreserved peripheral mononuclear cells (PBMC) is important for
      evaluating new vaccines in immune based therapies and in pathogenesis studies. To
      ensure comparable assay results from different laboratories and points of time,
      collaborative research in multicenter trials needs reliable and reproducible
      cryopreservation protocols that maintain cell viability and functionality.
      Current cryomedia consist largely of fetal bovine serum (FBS), a natural mix of
      growth factors, cytokines, and undefined compounds. Standardized procedures are
      not possible, as FBS can affect the antigen-specific T-cell response, the most
      important parameter in functionality assays. Also, worldwide sample exchange is
      complicated by the strict import restrictions on FBS, because of transfection
      risk. After establishing a serum-free cryopreservation protocol that maintains
      cell viability, recovery and antigen-specific T-cell response of PBMC comparably
      to FBS-based cryomedia (Germann et al., 2011), the aim of this study was the
      complete avoidance of animal proteins and products in combination with efficient
      cryopreservation. As long-term stability of the cryopreservation process is
      crucial for retrospective evaluation of samples at different points of time, PBMC
      were analyzed after storage for maximal four weeks and again after approximately
      six months. The cryopreservation efficiency of the protein-free and fully
      chemically defined cryomedium was comparable to FBS-medium after storage for few
      weeks and several months. Directly after thawing, this medium yielded viabilities
      over 97% and recovery values over 84%. Also, the specific T-cell functionality
      was preserved. Additionally, short-term and six month cryopreservation gave
      comparable results. The fully chemically defined medium presented here will
      increase standardization and reproducibility of analysis in multicenter-studies
      or in retrospective evaluation.

PMID- 22580763
TI  - Serine protease inhibitor A3 in atherosclerosis and aneurysm disease.
AB  - Remodeling of extracellular matrix (ECM) plays an important role in both
      atherosclerosis and aneurysm disease. Serine protease inhibitor A3 (serpinA3) is
      an inhibitor of several proteases such as elastase, cathepsin G and chymase
      derived from mast cells and neutrophils. In this study, we investigated the
      putative role of serpinA3 in atherosclerosis and aneurysm formation. SerpinA3 was
      expressed in endothelial cells and medial smooth muscle cells in human
      atherosclerotic lesions and a 14-fold increased expression of serpinA3n mRNA was
      found in lesions from Apoe-/- mice compared to lesion-free vessels. In contrast,
      decreased mRNA expression (-80%) of serpinA3 was found in biopsies of human
      abdominal aortic aneurysm (AAA) compared to non-dilated aortas. Overexpression of
      serpinA3n in transgenic mice did not influence the development of atherosclerosis
      or CaCl2-induced aneurysm formation. In situ zymography analysis showed that the
      transgenic mice had lower cathepsin G and elastase activity, and more elastin in
      the aortas compared to wild-type mice, which could indicate a more stable aortic
      phenotype. Differential vascular expression of serpinA3 is clearly associated
      with human atherosclerosis and AAA but serpinA3 had no major effect on
      experimentally induced atherosclerosis or AAA development in mouse. However,
      serpinA3 may be involved in a phenotypic stabilization of the aorta.

PMID- 22580764
TI  - Expectations of pain and accompanying symptoms during cancer treatment.
AB  - Patients' experience of cancer pain varies throughout the course of the disease.
      It is important to recognize that patients may experience more than one type of
      pain, and pain often occurs in the presence of other symptoms. Controlling pain
      requires a multi-faceted approach to assessing and treating the underlying
      mechanisms. This article reviews the pain mechanisms responsible for pain during
      cancer treatment and how expectations of pain and associated symptoms contribute
      to the pain experience.

PMID- 22580766
TI  - Chronic GVHD: Where are we? Where do we want to be? Will immunomodulatory drugs
      help?
AB  - Chronic GVHD (cGVHD) is an important problem after allotransplants. Some risk
      factors for cGVHD are similar to those of acute GVHD (aGVHD) but others are
      distinct indicating sometimes overlapping but unique pathogeneses. Precise
      incidence and prevalence data of cGVHD are lacking because of diverse diagnostic
      criteria but a 50% risk is a reasonable estimate. Incidence and prevalence of
      cGVHD are probably growing because of increased use of unrelated donors, blood
      rather than bone marrow (BM) grafts, decreased early transplant-related mortality
      (TRM) and increasing frequency of allotransplants. Pathophysiology of cGVHD is
      complex and poorly understood. Notably, no reliable surrogate end point to
      predict mechanism(s) of cGVHD has been identified. Therapy of cGVHD is
      unsatisfactory. Corticosteroids are effective but other drugs are controversial
      and few are rigorously tested in randomized trials. Highly variable response
      rates are reported because of small sample sizes and inconsistencies in
      eligibility, diagnostic and response criteria. We focus on the possible role of
      immunomodulatory drugs (IMiDs), thalidomide lenalidomide and pomalidomide, in
      preventing and treating cGVHD. The data suggest activity of thalidomide but at
      doses not clinically practical in many instances. There are few data with
      lenalidomide. Trials of pomalidomide, which has immune activities like
      thalidomide but with fewer adverse effects, are beginning. Because cGVHD is not
      recently reviewed in Bone Marrow Transplantation, we give a brief background and
      discuss challenges in diagnosing, understanding and treating cGVHD including the
      recently proposed National Institutes of Health consensus criteria for cGVHD.

PMID- 22580768
TI  - Defects in lymphocyte subsets and serological memory persist a median of 10 years
      after high-dose therapy and autologous progenitor cell rescue for malignant
      lymphoma.
AB  - The number of survivors having undergone high-dose therapy (HDT) followed by auto
      SCT continues to increase, although some of the long-term sequelae remain
      incompletely understood. The immunological status and quality of life of 37
      HDT/auto-SCT survivors with lymphoma in continuous remission of >=3 years were
      assessed alongside 14 age-matched controls. At a median follow-up of 10.5 years
      (range 2.2-20.2) following HDT/auto-SCT, the proportion of CD4(+) cells remained
      significantly reduced in patients compared with controls (median 43.4% vs 62.5%,
      respectively; P = < 0.001), predominantly a result of sustained reduction in the
      naive CD4(+) component (P < 0.001). Naive CD8(+) lymphocytes (P = 0.014) and
      transitional B cells (P = 0.008) were also significantly reduced, but differences
      in other lymphocyte subsets were not observed. Uptake of revaccination following
      HDT/auto-SCT was sporadic; between 11% and 33% of patients had serological titres
      outside the protective ranges for five of six routinely used vaccines. In the
      main, patients were found to have a good quality of life, although their EORTC
      QLQ-C30 questionnaire scores were significantly lower for the physical and social
      functioning domains compared with controls. Ten years after HDT/auto-SCT
      immunological deficits persist; to avoid excess risk of preventable disease,
      serological immunity should be assessed post HDT/auto-SCT followed by appropriate
      revaccination.

PMID- 22580767
TI  - Anti-thymocyte globulin for conditioning in matched unrelated donor hematopoietic
      cell transplantation provides comparable outcomes to matched related donor
      recipients.
AB  - Rabbit anti-thymocyte globulin (ATG) is used as prophylaxis against GVHD
      following allogeneic hematopoietic cell transplantation (HCT). At our
      institution, ATG is exclusively used in the conditioning of matched unrelated
      donor (URD) transplant recipients. A total of 50 URD HCT recipients who received
      ATG (ATG group) were retrospectively compared with 48 matched related donor (MRD)
      HCT recipients who did not receive ATG (no ATG group). There were no significant
      differences between the groups in rates of day 100 mortality, acute GVHD or
      relapse. Chronic GVHD incidence was significantly lower in the ATG group (P =
      0.007). At a median follow-up of 36 months in the entire cohort, 50% patients are
      alive in the ATG group and 63% of the patients are alive in the no ATG group (P =
      0.13). We conclude that the administration of ATG to patients undergoing URD HCT
      preserves the anti-leukemia benefit of the transplant, while reducing the risk of
      developing GVHD, resulting in OS rates that are comparable to MRD HCT recipients.

PMID- 22580769
TI  - Successful response to infliximab of recurrent pericardial graft versus host
      disease in a pediatric patient.

PMID- 22580770
TI  - Increased alpha1-antitrypsin levels in acute-phase Kawasaki disease as shown by
      SELDI-TOF MS analysis.
AB  - Various agents have been suggested as causal or associated factors in the
      pathogenesis of Kawasaki disease (KD); however, the underlying factors of KD
      remain unknown. Plasma exchange is one of the most effective treatments for the
      acute phase of KD. This indicates that plasma may contain factors associated with
      the pathogenesis of KD. To search for proteins that may be involved in KD
      pathogenesis, we analyzed serum proteins with surface-enhanced laser
      desorption/ionization time of flight mass spectrometry (SELDI-TOF MS). Serum
      samples were obtained from 17 KD patients. Serum from six of the patients was
      collected during acute phase before acetylsalicylic acid (ASA) and intravenous
      immunoglobulin administration (phase A1), during remission with ASA (phase A2),
      and during remission without any medication (phase A3). Serum from the remaining
      11 patients was collected for phases A1 and A2 only. There were two age- and sex
      matched control groups comprising 8 afebrile healthy children (group B) and 8
      febrile children with several infectious diseases (group C). There were no
      statistical differences in laboratory examination between phase A1 and group C
      except for albumin level, alanine aminotransferase, or sodium level. Serum
      samples were analyzed by SELDI-TOF MS after purification. We detected five peaks,
      i.e., those were specifically increased or decreased during phase A1, and
      identified 1 of these as alpha1-antitrypsin (alpha1-AT). alpha1-AT can inhibit
      neutrophil elastase activity. This elastase is thought to play a role in coronary
      artery damage. Our findings present an interesting starting point for further
      investigations into the pathophysiology of KD.

PMID- 22580771
TI  - Surgical removal of pulmonary arteriovenous malformations subsequent to total
      cavopulmonary connection conversion long after a Bjork procedure.
AB  - Because the cavopulmonary shunt procedure is widely used for palliation of
      complex congenital heart diseases, pulmonary arteriovenous malformations (PAVMs)
      are relatively well-known complications. The reported patient was a 23-year-old
      woman who experienced PAVMs in the right lower lobe after a classical Glenn
      anastomosis and Bjork procedure for tricuspid atresia. Her arterial oxygen
      saturation (SaO2) 14 years after the Bjork procedure was ~80 %. She then
      underwent a total cavopulmonary connection (TCPC) conversion to reduce her PAVMs
      in the right lower lobe using the "hepatic factor." However, her situation
      remained unchanged, and she experienced severe systemic cyanosis (SaO2, 70 %) and
      dyspnea during physical exertion without hemoptysis due to increased blood flow
      to the PAVMs. Although interventional embolization was considered, it was
      impossible due to considerable dilation of the main PAVM. Thus, right lower lung
      lobectomy was performed. After surgery, the patient's SaO2 increased to 90 %. To
      the authors' knowledge, this is the first case report of a lung resection for
      residual PAVMs after TCPC conversion.

PMID- 22580772
TI  - Transcatheter ventricular septal defect (VSD) creation for restrictive VSD in
      double-outlet right ventricle.
AB  - BACKGROUND: Double-outlet right ventricle (DORV) with a restrictive ventricular
      septum is a rare but highly morbid phenomenon that can be complicated by
      progressive left ventricular hypertrophy, arrhythmias, aneurysm formation, severe
      pulmonary hypertension, and death in the newborn. Surgical creation or
      enlargement of a ventricular septal defect (VSD) is palliative but may damage the
      conduction system or the atrioventricular valves in the newborn. This report
      presents a transcatheter approach to palliation for a newborn that had DORV with
      a restrictive ventricular septum. METHODS/RESULTS: A full-term infant girl (2.9
      kg) referred for hypoxia (80% with room air) and murmur was found to have DORV,
      interrupted inferior vena cava, and restrictive VSD (95-mmHg gradient).
      Transhepatic access was performed, and an internal mammary (IM) catheter was
      advanced through the atrial septal defect and into the left ventricle. By
      transesophageal echocardiographic guidance, a Baylis radiofrequency perforation
      wire was used to cross the ventricular septum, and the defect was enlarged using
      a 4-mm cutting balloon. A bare metal stent then was deployed to maintain the
      newly created VSD. The patient did well after the procedure but required
      pulmonary artery banding 4 days later. She returned 5 months later with cyanosis
      and the development of obstructing right ventricle muscle bundles, requiring
      further surgical palliation. CONCLUSIONS: This report describes the first
      transcatheter creation of VSD in DORV with a restrictive ventricular septum in a
      newborn infant. Use of the radiofrequency catheter in combination with cutting
      balloon dilation and stent implantation is an efficient method for creating a VSD
      in such a patient.

PMID- 22580773
TI  - A rare case of left lung hypoplasia associated with congenital pulmonary artery
      aneurysm and ventricular septal defect.
AB  - This report describes a 3-year-old boy who presented with hemoptysis and a
      history of congenital heart disease detected at the age of 3 months. Clinical and
      laboratory evaluation showed a large true congenital pulmonary artery aneurysm of
      the left main pulmonary artery occupying the entire left hemithorax and two small
      aneurysms in the right lung. In addition, a restricted ventricular septal defect
      was detected. It was evident on clinical and histologic grounds that the multiple
      aneurysms seen in this child stemmed from congenital weakness of the arterial
      wall in conjunction with increased pulmonary blood flow and elevated pulmonary
      artery pressure.

PMID- 22580774
TI  - Anomalous drainage of the inferior caval vein to the left atrium diagnosed by
      enhanced multidetector computed tomography.

PMID- 22580775
TI  - Aortic regurgitation associated with critical aortic stenosis in a fetus.
AB  - Aortic regurgitation in association with aortic stenosis is rare in the fetus.
      Findings have shown that severe aortic regurgitation is worsened by the increase
      in systemic vascular resistance after birth, resulting in low cardiac output,
      hypoxemia, and neonatal death. This report describes a unique case of aortic
      regurgitation with aortic stenosis, severe mitral regurgitation, retrograde flow
      in the aortic arch, and an enormous left atrium with a restrictive foramen ovale
      in a fetus. In this case, aortic regurgitation was diminished immediately after
      birth, indicating that spontaneous improvement in aortic regurgitation after
      birth should be taken into account when the final prognosis is predicted.

PMID- 22580776
TI  - Congenital aneurysm of the right atrial appendage in a fetus.

PMID- 22580777
TI  - Bilateral absence of superior vena cava.
AB  - The absence of a right superior vena cava (SVC) in situs solitus is very rare,
      and even then it is usually associated with left SVC. There have been few case
      reports in the literature of isolated bilateral absence of SVC. Bilateral absent
      SVC can have clinical implication, including pacemaker placements, central venous
      line placement, monitoring, and occasionally associated anomalies. We describe a
      case detected on fetal echocardiogram with bilateral absent SVC and structurally
      normal heart.

PMID- 22580779
TI  - Patient specific implants for amputation prostheses: design, manufacture and
      analysis.
AB  - OBJECTIVES: To design, manufacture and analyze custom implants with functional
      gradation in macrostructure for attachment of amputation prostheses. METHODS: The
      external shape of the implant was designed by extracting geometrical data of
      canine cadavers from computed tomography (CT) scans to suit the bone cavity.
      Three generations of implant designs were developed and were optimized with the
      help of fit/fill and mechanical performance of implant-cadaver bone assembly
      using CT analysis and compression testing, respectively. A final optimized,
      custom Ti6Al4V alloy amputation implant, with approximately 25% porosity in the
      proximal region and approximately zero percent porosity in the distal region, was
      fabricated using Laser Engineered Net Shaping (LENSTM)--a laser based additive
      manufacturing technology. RESULTS: The proposed design changes in the second
      generation designs, in terms of refining thresholds, increased the average fill
      of the bone cavity from 58% to 83%. Addition of a flange between the stem and the
      head in the second generation designs resulted in more than a seven-fold increase
      in the compressive load carrying capacity of the assembly. Application of LENSTM
      in the fabrication of present custom fit Ti6Al4V alloy implants enabled
      incorporation of 20 to 30% porosity in the proximal region and one to two percent
      residual porosity in the distal portion of the implant. CLINICAL SIGNIFICANCE:
      Patient specific prostheses having direct connection to the skeletal structure
      can potentially aid in problems related to load transfer and proprioception in
      amputees. Furthermore, application of LENSTM in the fabrication of custom
      implants can be faster to incorporate site specific porosity and gradients for
      improving long-term stability.

PMID- 22580780
TI  - Radiographic evaluation of Gustafson's criteria for the purpose of forensic age
      diagnostics.
AB  - The main criteria used in dental age estimation in living young individuals are
      mineralisation and eruption of the third molars. In order to further diversify
      the spectrum of characteristics after completion of third molar development,
      tests were undertaken to determine whether the characteristics studied by
      Gustafson can be ascertained with the required forensic certainty with the aid of
      the orthopantomogram and whether the evaluation of these could render forensic
      odontological age diagnoses possible beyond the 18th year of life. For this
      purpose, 1,299 conventionally produced orthopantomograms of 650 female and 649
      male Germans aged from 15 to 40 years were studied. The characteristics of
      secondary dentin formation, cementum apposition, periodontal recession and
      attrition were evaluated in all the mandibular premolars. The correlation of the
      individual characteristics with chronological age was studied with the aid of a
      multiple regression analysis in which chronological age formed the dependent
      variable. Depending on the tooth studied, the R values amounted to 0.65 to 0.73;
      the standard error of estimate was 5.3 to 5.7 years. Basically, the regression
      equations calculated can be recommended for age estimation in living individuals,
      although it should be borne in mind that the applicability of the new method
      presented is limited by the quality of the X-ray images.

PMID- 22580782
TI  - Bully renal cysts knock down urine-concentrating capacity in the early rounds.

PMID- 22580781
TI  - Murine toxicology and pharmacokinetics evaluation of retinoic acid metabolism
      blocking agent (RAMBA), VN/12-1.
AB  - PURPOSE: Novel retinoic acid metabolism blocking agent (RAMBA), VN/12-1, is a
      highly potent anti-cancer agent that induces autophagy. Its combination with
      autophagy inhibitor chloroquine (CHL) has been shown to synergistically enhance
      apoptosis in breast cancer cells. The purpose of this study was to determine the
      toxicity and pharmacokinetic profile of VN/12-1 and its combination with CHL.
      METHODS: Preliminary toxicology of VN/12-1 was determined using female SCID mice
      (n = 4 for each group). ATRA was used for comparison. We selected four different
      doses of VN/12-1 and ATRA. Two of the doses were low and less frequent (2.5 and 5
      mg/kg twice a week), and the remaining doses were high and more frequent (10 and
      20 mg/kg every day). The dose of CHL was 50 mg/kg twice a week. For
      pharmacokinetic (PK) study, 20 mg/kg of VN/12-1 was injected subcutaneously
      (s.c.) into the mice, and their plasma was collected at various intervals (n = 2)
      and analyzed by HPLC. RESULTS: The lower and less frequent doses of VN/12-1 and
      ATRA were found to be least toxic. However, high and more frequent doses of these
      compounds were toxic to the mice. PK results showed that VN/12-1 has a half-life
      of 6 h. The area under the curve (AUC) for VN/12-1 was 83.78 h MUg/ml.
      CONCLUSIONS: VN/12-1 and ATRA are non-toxic when used as 5 mg/kg twice a week as
      single agents or in combination with CHL. The favorable PK properties of VN/12-1
      can potentially be used for its further advanced pre-clinical and clinical
      development.

PMID- 22580783
TI  - Subclinical cardiac abnormalities and kidney function decline: the multi-ethnic
      study of atherosclerosis.
AB  - BACKGROUND AND OBJECTIVES: Clinical heart failure (HF) is associated with CKD and
      faster rates of kidney function decline. Whether subclinical abnormalities of
      cardiac structure are associated with faster kidney function decline is not
      known. The association between cardiac concentricity and kidney function decline
      was evaluated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a
      longitudinal study of 3866 individuals from the Multi-Ethnic Study of
      Atherosclerosis (2000-2007) who were free of clinical cardiovascular disease,
      with an estimated GFR (eGFR) >=60 ml/min per 1.73 m(2) at baseline and 5 years of
      follow-up. Concentricity, a measurement of abnormal cardiac size, was assessed by
      magnetic resonance imaging and evaluated as a continuous measurement and in
      quartiles. GFR was estimated by creatinine (eGFRcr) and cystatin C (eGFRcys). The
      association of concentricity with annual eGFR decline, incident CKD, and rapid
      kidney function decline (>5% per year) was investigated using linear mixed models
      as well as Poisson and logistic regression, respectively. Analyses adjusted for
      demographics, BP, diabetes, and inflammatory markers. RESULTS: Median decline was
      -0.8 (interquartile range, -3.1, -0.5) by eGFRcr. Compared with the lowest
      quartile of concentricity, persons in the highest quartile had an additional 21%
      (9%-32%) decline in mean eGFRcr in fully adjusted models. Concentricity was also
      associated with incident CKD and with rapid kidney function decline after
      adjustment. CONCLUSIONS: Subclinical abnormalities in cardiac structure are
      associated with longitudinal kidney function decline independent of diabetes and
      hypertension. Future studies should examine mechanisms to explain these
      associations.

PMID- 22580784
TI  - Nephrology quiz and questionnaire: renal replacement therapy.
AB  - Presentation of the Nephrology Quiz and Questionnaire has become an annual
      "tradition" at the meetings of the American Society of Nephrology. It is a very
      popular session judged by consistently large attendance. Members of the audience
      test their knowledge and judgment on a series of case-oriented questions prepared
      and discussed by experts. They can also compare their answers in real time, using
      audience response devices, with those of program directors of nephrology training
      programs in the United States, acquired through an Internet-based questionnaire.
      Topics presented here include fluid and electrolyte disorders, transplantation,
      and ESRD and dialysis. Cases representing each of these categories along with
      single best answer questions were prepared by a panel of experts (Drs. Palmer,
      Hricik, and Golper, respectively). After the audience responses, the "correct"
      and "incorrect" answers then were briefly discussed and the results of the
      questionnaire were displayed. This article aims to recapitulate the session and
      reproduce its educational value for a larger audience-readers of the Clinical
      Journal of the American Society of Nephrology. Have fun.

PMID- 22580785
TI  - Detected renal cysts are tips of the iceberg in adults with ADPKD.
AB  - BACKGROUND AND OBJECTIVES: In autosomal dominant polycystic kidney disease,
      progressive renal enlargement secondary to expanding cysts is a hallmark. The
      total cyst load and range of cyst diameters are unknown. The purpose of this
      study was to quantify the total number and range of diameters of individual cysts
      in adults with preserved GFR. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A
      retrospective, morphometric analysis of renal cyst number and diameter using
      magnetic resonance images from eight adult autosomal dominant polycystic kidney
      disease patients was performed at baseline and after 6.9 years. Cyst number and
      diameter were measured in microscopic sections of nephrectomy specimens from five
      different adults. RESULTS: The diameters of 1010 cysts ranged from 0.9 to 77.1 mm
      in baseline T2 magnetic resonance images, and the mean total number of cysts
      increased from 682 to 1002 in 6.9 years. However, magnetic resonance imaging
      detects only cysts above the lower limit of detection. In 405 cysts measured in
      nephrectomy specimens, 70% had diameters <0.9 mm. Cyst counts by magnetic
      resonance in eight subjects compared with histology revealed approximately 62
      times more cysts below the limit of magnetic resonance imaging detection than
      above it. CONCLUSIONS: This study presents quantitative data indicating that
      renal cysts develop in a minority of renal tubules. Increased numbers detected by
      magnetic resonance imaging are caused primarily by cysts below detection at
      baseline enlarging to a detectable diameter over time. The broad range of
      diameters, with a heavy concentration of microscopic cysts, may be most
      appropriately explained by a formation process that operates continuously
      throughout life.

PMID- 22580786
TI  - Circulating and urinary microRNAs in kidney disease.
AB  - microRNAs are small, noncoding RNAs that control gene/protein expression through
      target messengerRNA degradation and/or inhibition of protein synthesis. An array
      of experimental studies has shown the importance of microRNAs for disease
      initiation/progression. microRNAs are generally considered to act as
      intracellular modulators of gene expression. However, first studies in the cancer
      and cardiovascular field have elucidated that microRNAs are remarkably stable in
      the extracellular compartment (e.g., in blood or urine). The detection and
      quantification of circulating microRNAs may, thus, represent a novel noninvasive
      tool to detect and monitor disease activity. In addition, there might be a
      potential biologic relevance of circulating microRNAs for cell/cell
      communication. The aim of the present article is to give an outline of recent
      work on circulating and urinary microRNAs as well as their potential paracrine
      activity in kidney disease.

PMID- 22580787
TI  - Female sexual dysfunction in ESRD: an underappreciated epidemic?

PMID- 22580788
TI  - Nephrology quiz and questionnaire: electrolytes.
AB  - Presentation of the Nephrology Quiz and Questionnaire has become an annual
      tradition at the meetings of the American Society of Nephrology. It is a very
      popular session judged by consistently large attendance. Members of the audience
      test their knowledge and judgment on a series of case-oriented questions prepared
      and discussed by experts. They can also compare their answers in real time using
      audience response devices with the answers of program directors of nephrology
      training programs in the United States through an Internet-based questionnaire.
      Topics presented here include fluid and electrolyte disorders, transplantation,
      and ESRD and dialysis. Cases representing each of these categories along with
      single best-answer questions were prepared by a panel of experts (the authors).
      The correct and incorrect answers then were briefly discussed after the audience
      responses and the results of the questionnaire were displayed. This article tries
      to recapitulate the session and reproduce its educational value for a larger
      audience-the readers of the Clinical Journal of the American Society of
      Nephrology. Have fun.

PMID- 22580789
TI  - Metal pollution and ecological risk assessment in marine sediments of Karachi
      Coast, Pakistan.
AB  - Concentrations of 12 metals (Fe, Mn, Cr, Mo, Ni, Pb, Se, Sr, U, V, Zn, and Zr) in
      surface sediments of Karachi Coast, Pakistan were determined to evaluate their
      distribution and pollution assessment. The measured metals in the sediments were
      found to be in the range of Fe, 0.84-6.96 %; Mn, 300-1,300 MUg/g; Cr, 12.0-319.84
      MUg/g; Mo, 0.49-2.03 MUg/g; Ni, 1.53-58.86 MUg/g; Pb, 9.0-49.46 MUg/g; Se, 0.25
      .86 MUg/g; Sr, 192-1185 MUg/g; U, 0.19-1.66 MUg/g; V, 15.80-118.20 MUg/g; Zn,
      15.60-666.28 MUg/g; and Zr, 44.02-175.26 MUg/g. The mean contents of the metal
      studied were: Fe, 3.07 %, Mn, 0.05 %; Cr, 96.75 MUg/g; Mo, 1.34 MUg/g; Ni, 31.39
      MUg/g; Pb, 23.24 MUg/g; Se, 0.61 MUg/g; Sr, 374.83 MUg/g; U, 0.64 MUg/g; V, 61.75
      MUg/g; Zn, 204.75 MUg/g; and Zr:76.27 MUg/g, and arrangement of the metals from
      higher to lower mean content in this area is: Fe > Zn > Mn > Sr > Zn > Cr > Zr >
      V > Ni > Pb > Mo > U > Se. There is no significant correlation among most of
      these metals, indicating different anthropogenic and natural sources. To assess
      ecotoxic potential of marine sediments, Numerical Sediment Quality Guidelines
      were also applied. The concentration of Pb in all the sediments except one was
      lower than the threshold effect concentration (TECs) showing that there are no
      harmful effects to marine life from Pb. On the other hand, the concentrations of
      Cr, Ni, and Zn exceeded TEC in three stations, indicating their potential risk.
      The degree of pollution in sediments for metals was assessed by calculating
      enrichment factor (EF) and pollution load index (PLI). The results indicated that
      sediments of Layari River Mouth Area, Fish Harbour, and KPT Boat Building Area
      are highly enriched with Cr and Zn (EF > 5). Sediments of Layari River Outfall
      Zone were moderately enriched with Ni and Pb (EF > 2). The pollution load index
      was found in the range of 0.98 to 1.34. Lower values of PLI (<= 1) at most of
      sampling locations imply no appreciable input from anthropogenic sources.
      However, relatively higher PLI values (>1) at Layari River Mouth Area, Fish
      Harbour, and KPT Boat Building Area are attributed to increased human activity in
      the area.

PMID- 22580790
TI  - Flow injection online spectrophotometric determination of uranium after
      preconcentration on XAD-4 resin impregnated with nalidixic acid.
AB  - In this work, spectrophotometer was used as a detector for the determination of
      uranium from water, biological, and ore samples with a flow injection system
      coupled with solid phase extraction. In order to promote the online
      preconcentration of uranium, a minicolumn packed with XAD-4 resin impregnated
      with nalidixic acid was utilized. The system operation was based on U(VI) ion
      retention at pH 6 in the minicolumn at flow rate of 15.2 mL min(-1). The uranium
      complex was removed from the resin by 0.1 mol dm(-3) HCl at flow rate of 3.2 mL
      min(-1) and was mixed with arsenazo III solution (0.05 % solution in 0.1 mol dm(
      3) HCl, 3.2 mL min(-1)) and driven to flow through cell of spectrophotometer
      where its absorbance was measured at 651 nm. The influence of chemical (pH and
      HCl (as eluent and reagent medium) concentration) and flow (sample and eluent
      flow rate and preconcentration time) parameters that could affect the performance
      of the system as well as the possible interferents was investigated. At the
      optimum conditions for 60 s preconcentration time (15.2 mL of sample volume), the
      method presented a detection limit of 1.1 MUg L(-1), a relative standard
      deviation (RSD) of 0.8 % at 100 MUg L(-1), enrichment factor of 30, and a sample
      throughput of 42 h(-1), whereas for 300 s of the preconcentration time (76 mL of
      sample volume), a detection limit of 0.22 MUg L(-1), a RSD of 1.32 % at 10 MUg L(
      1), enrichment factor of 150, and a sampling frequency of 11 h(-1) were reported.

PMID- 22580792
TI  - Visitor impact on rocky shore communities of Qeshm Island, the Persian Gulf,
      Iran.
AB  - The influence of visitors on macroinvertebrates of rocky intertidal shores was
      investigated in southern coasts of the Qeshm Island, the Persian Gulf, Iran.
      Qeshm Island located at the Strait of Hormuz, with an area of 1,491 km(2), is the
      largest island in the region. This island consists of a number of important
      natural habitat types including creeks, mangroves, corals, and sandy, muddy, and
      rocky shores that accommodate diverse marine flora and fauna communities. Two
      rocky shores were selected at the touristic beaches being visited regularly, and
      further two control locations selected at pristine shores. Intertidal
      macroinvertebrates were collected from six microhabitats including rock
      platforms, cobbles, boulders, crevices, sea walls, and rock pools during two
      different periods representing high and low tourist seasons. Species richness,
      density, and assemblage structure in heavily visited shores were compared with
      that of control locations. Striped barnacles (Balanus amphitrite) were present on
      platforms of all locations, thus the changes in their size were used as the
      obvious contrast associated with visitor's impact. A total of 70
      macroinvertebrate species from 11 phyla were recorded. Significant differences
      were detected in taxonomic richness, density, and assemblage structure of
      macroinvertebrates between heavily visited and pristine shores, suggesting that
      macroinvertebrates were adversely affected by visitors' impact at heavily visited
      shores. The test of changes in species richness, density, and assemblage
      structure from high to low seasons yielded mixed results. The significant changes
      in density and assemblage structure from high to low seasons were only observed
      in one heavily visited shore. A significant reduction in size of striped
      barnacles was observed only in one heavily visited shore. The opportunistic or
      fugitive species (e.g., small macroalgae and barnacles) were dominant
      macroinvertebrates on heavily visited shores indicating early succession stage.
      The results presented here showed that macroinvertebrates were adversely affected
      by human activities in subtropical rocky shore.

PMID- 22580791
TI  - Blood lead levels, delta-ALAD inhibition, and hemoglobin content in blood of
      giant toad (Rhinella marina) to assess lead exposure in three areas surrounding
      an industrial complex in Coatzacoalcos, Veracruz, Mexico.
AB  - The Coatzacoalcos Region in Veracruz, Mexico houses one of the most important
      industrial complexes in Mexico and Latin America. Lead is an ubiquitous
      environmental pollutant which represents a great risk to human health and
      ecosystems. Amphibian populations have been recognized as biomonitors of changes
      in environmental conditions. The purpose of this research is to measure exposure
      to lead and evaluate hematological and biochemical effects in specimens of giant
      toads (Rhinella marina) taken from three areas surrounding an industrial complex
      in the Coatzacoalcos River downstream. Lead levels in toads' blood are between
      10.8 and 70.6 MUg/dL and are significantly higher in industrial sites. We have
      found a significant decrease in the delta-aminolevulinic acid dehydratase (delta
      ALAD) activity in blood from 35.3 to 78 % for the urban-industrial and industrial
      sites, respectively. In addition, we have identified a strong inverse
      relationship between the delta-ALAD activity and the blood lead levels (r = 
      0.84, p < 0.001). Hemoglobin and mean corpuscular hemoglobin levels, as well as
      the condition factor, are found to be lower at industrial sites compared with the
      reference sites. Our results suggest that the R. marina can be considered a good
      biomonitor of the delta-ALAD activity inhibition and hematological alterations at
      low lead concentrations.

PMID- 22580793
TI  - Polymorphisms of intron 1 and the promoter region at the PRNP gene in BSE-free
      Caracu cattle.
AB  - The infectious prion protein PrP(Sc) is encoded by the PRNP gene. In cattle,
      insertion/deletion (indel) polymorphisms are among the changes that occur in this
      gene, the most studied of which are within intron 1 (12 bp) and the promoter
      region (23 bp). Sequence variants in this gene may affect the formation of
      PrP(Sc). In the present study, nucleotide variability in specific regions of the
      PRNP gene in Caracu cattle free of bovine spongiform encephalopathy was
      investigated to determine the genotypic profile of each animal within the group.
      Caracu cattle exhibited high allele frequency for the two polymorphic regions
      studied, 12ins (70 %) and 23ins (72.5 %), genotype frequencies of 50 % for
      12ins/ins and 50 % for 23ins/del, and a high frequency of the 12ins-23ins
      haplotype (57.5 %). Of the 40 animals sampled, 15 had the 12ins-23ins/12ins-23ins
      diplotype.

PMID- 22580794
TI  - Genotype frequencies of drug-metabolizing enzymes responsible for purine and
      pyrimidine antagonists in a healthy Asian-Indian population.
AB  - Purine and pyrimidine antimetabolites are used to treat leukemias, autoimmune
      diseases, and solid tumors. Detection of slow metabolizers before administration
      of the drugs is necessary to prevent any subsequent drug toxicity. With this aim,
      we determined the frequencies of normal and slow alleles in our population.
      Polymorphisms in genes encoding cytidine deaminase (CDA), dihydropyrimidine
      dehydrogenase (DPYD), and thiopurine-S-methyltransferase (TPMT) were documented
      in 225 healthy volunteers. The polymorphisms typed included CDA*3, DPYD*2A,
      TPMT*2A, TPMT*3B, and TPMT*3C. Methods used for genotyping included standard PCR
      RFLP and allele-specific PCR reactions. The frequencies were 0.44 % for DPYD*2A,
      0.67 % for TPMT*3B, and 0.89 % for TPMT*3C. The CDA*3 and TPMT*2A alleles were
      not detected. Although these polymorphisms have been demonstrated to be
      associated with drug toxicity in other populations, they appear to be very rare
      in the adult Indian population.

PMID- 22580795
TI  - Molecular characterization of prolactin cDNA and its expression pattern in skin
      tissue of Liaoning Cashmere goat.

PMID- 22580796
TI  - Removal and recovery of uranium (VI) from aqueous solutions by immobilized
      Aspergillus niger powder beads.
AB  - The immobilized Aspergillus niger powder beads were obtained by entrapping
      nonviable A. niger powder into Ca-alginate gel. The effects of pH, contact time,
      initial uranium (VI) concentration and biomass dosage on the biosorption of
      uranium (VI) onto the beads from aqueous solutions were investigated in a batch
      system. Biosorption equilibrium data were agreeable with Langmuir isotherm model
      and the maximum biosorption capacity of the beads for uranium (VI) was estimated
      to be 649.4 mg/g at 30  degrees C. The biosorption kinetics followed the pseudo
      second-order model and intraparticle diffusion equation. The variations in
      enthalpy (26.45 kJ/mol), entropy (0.167 kJ/mol K) and Gibbs free energy were
      calculated from the experimental data. SEM and EDS analysis indicated that the
      beads have strong adsorption capability for uranium (VI). The adsorbed uranium
      (VI) on the beads could be released with HNO(3) or HCl. The results showed that
      the immobilized A. niger powder beads had great potential for removing and
      recovering uranium (VI) from aqueous solutions.

PMID- 22580797
TI  - Communities of different plant diversity respond similarly to drought stress:
      experimental evidence from field non-weeded and greenhouse conditions.
AB  - Accelerating rate of species loss has prompted researchers to study the role of
      species diversity in processes that control ecosystem functioning. Although
      negative impact of species loss has been documented, the evidence concerning its
      impact on ecosystem stability is still limited. Here, we studied the effects of
      declining species and functional diversity on plant community responses to
      drought in the field (open to weed colonization) and greenhouse conditions. Both
      species and functional diversity positively affected the average yields of field
      communities. However, this pattern was similar in both drought-stressed and
      control plots. No effect of diversity on community resistance, biomass recovery
      after drought and resilience was found because drought reduced biomass production
      similarly at each level of diversity by approximately 30%. The use of
      dissimilarity (characterized by Euclidean distance) revealed higher variation
      under changing environments (drought-stressed vs. control) in more diverse
      communities compared to less species-rich assemblages. In the greenhouse
      experiment, the effect of species diversity affected community resistance,
      indicating that more diverse communities suffered more from drought than species
      poor ones. We conclude that our study did not support the insurance hypothesis
      (stability properties of a community should increase with species richness)
      because species diversity had an equivocal effect on ecosystem resistance and
      resilience in an environment held under non-weeded practice, regardless of the
      positive relationship between sown species diversity and community biomass
      production. More species-rich communities were less resistant against drought
      stressed conditions than species-poor ones grown in greenhouse conditions.

PMID- 22580798
TI  - Zeolitic Imidazolate framework-8 as efficient pH-sensitive drug delivery vehicle.
AB  - Zeolitic Imidazolate Framework-8 (ZIF-8), for the first time for ZIFs, exhibits a
      remarkable capacity for the anticancer drug 5-fluorouracil (5-FU), around 660 mg
      of 5-FU/g of ZIF-8, and presents a pH-triggered controlled drug release property.
      These prove ZIF-8 to be a valuable candidate for delivery of anticancer agents
      and reveal its potential applications in the treatment of cancer.

PMID- 22580799
TI  - Stereotactic iodine-125 brachytherapy for treatment of inoperable focal brainstem
      gliomas of WHO grades I and II: feasibility and long-term outcome.
AB  - Microsurgical resection is the most frequently suggested treatment option for
      accessible focal brainstem gliomas (F-BSG) of World Health Organization (WHO)
      grades I and II. Because of their location in the highly eloquent brain, however,
      resection is associated with permanent postoperative morbidity, ranging from 12
      to 33 %. Only a few reports have suggested stereotactic brachytherapy (SBT) with
      implantation of iodine-125 seeds as a local treatment alternative. Between 1993
      and 2010, 47 patients were treated with SBT (iodine-125 seeds; cumulative surface
      dose 50-65 Gy) for inoperable F-BSG, WHO grades I and II, in one of the largest
      reported patient series. We evaluated procedure-related complications, clinical
      outcome, and progression-free and overall survival (PFS, OS). Median follow-up
      was 81.6 months. Procedure-related mortality was zero. Within 30 days of seed
      implantation six patients (12.8 %) had transient neurological deficits. Two
      patients (4.3 %) deteriorated permanently. Space-occupying cysts occurred in six
      patients (12.8 %) after a median of 28.5 months, and required surgical
      intervention. Nine patients (19.1 %) presented with tumor relapse after a median
      of 56.6 months (range 7.9-118.0 months). For the remaining 38 patients complete
      response was observed for 23.4 %, partial response for 29.8 %, and stable disease
      for 27.7 %. Actuarial PFS was 97.7 +/- 2.2, 92.8 +/- 4.0, 81.2 +/- 6.5, and 62.0
      +/- 10.4 % after 1, 2, 5, and 10 years, respectively. Corresponding OS was 100 +/
      0.0 % (1 and 2 years), 97.4 +/- 2.6 % (5 years), and 87.6 +/- 7.0 % (10 years).
      SBT is a comparatively safe, minimally invasive, and highly effective local
      treatment option for patients with inoperable F-BSG WHO grades I and II; it
      merits further evaluation in prospective randomized trials.

PMID- 22580800
TI  - Acute stroke treatment using the Penumbra endovascular mechanical thrombolysis
      device: a single-centre experience.
AB  - PURPOSE: Ischaemic stroke due to occlusion of large cerebral vessels has a poor
      prognosis. The clinical outcome is related to efficacy and timing of
      recanalisation of the occluded arteries. We report our experience with a thrombus
      aspiration device (Penumbra), and focus on pre- and postprocedural management.
      MATERIALS AND METHODS: We retrospectively reviewed 18 consecutive patients with
      acute ischaemic stroke due to the occlusion of large cerebral vessels who were
      treated with mechanical thrombolysis at our centre between September 2009 and
      July 2010. Preprocedural symptoms were quantified using the National Institutes
      of Health Stroke Scale (NIHSS). Mechanical thrombolysis was performed with the
      Penumbra system. Intravenous thrombolysis was done only if <3 h had elapsed since
      symptom onset. Associated vessel stenoses were treated with stenting. All
      patients underwent neurological examination and postprocedural magnetic resonance
      angiography (MRA) at 3 and 6 months. RESULTS: Mechanical thrombolysis using the
      Penumbra system was performed in all cases. A total of 83% of treated vessels had
      a value of 2/3 according to the Thrombolysis in Cerebral Infarction (TICI) scale.
      In seven patients (39%) intravenous thrombolysis was unsuccessful, and salvage
      mechanical thrombolysis followed. Three patients died after the procedure
      (16.7%). Five patients (27.8%) required a stenting procedure. All patients
      reported a significant improvement in symptoms (mean baseline NIHSS 19.6+/-5.6;
      mean postprocedural NIHSS, 7.8+/-5.5 p<0.0001) CONCLUSIONS: Our preliminary
      experience with the Penumbra mechanical thrombolysis system confirms previously
      reported results showing the efficacy and safety of the device in treating acute
      stroke caused by the occlusion of large intracranial vessels.

PMID- 22580801
TI  - A computed tomography-based comparative cephalometric analysis of the Italian
      craniofacial pattern through 2,700 years.
AB  - The aim of our study was to define the changes in morphovolumetric features of
      neurocranium, basicranium and splanchnocranium in the population of Campania,
      southern Italy, over the last 2,700 years. This was a very intense period for
      this region from both historical and evolutionary perspectives and was marked by
      the succession of colonisations, dominations and invasions by several European
      and non-European peoples, events that profoundly influenced the original genetic
      heritage, which subsequently became more complex. Unlike most previous authors,
      we based our craniometric comparative analysis on multidetector computed
      tomography (MDCT) studies of contemporary and ancient series dating to between
      the seventh and fifth centuries B.C. of skulls found in the Etruscan necropolis
      of Pompei and Pontecagnano. MDCT is extremely reliable in identifying landmarks
      and measuring linear and angular indices through the use of multiplanar and
      tridimensional reformations. While highlighting a remarkable stability of 22/32
      of the indices considered, as an effect of the role of the genetic heritage in
      preserving morphovolumetric features in a given population, statistical analysis
      showed some interesting results: the main changes concerned the splanchnocranium
      and the occlusion, indicating a higher sensitivity of these districts to
      environmental factors, mainly related to diet. Conversely, neurobasicranial
      complex morphovolumetric features remained amazingly intact. In particular, the
      neurocranium increased in overall capacity in response to the growing brain and
      changed shape with a progressive shift to a dolichocranic, flattened frontal
      pattern; the basicranium shape was preserved, as indicated by the stability of
      the cranial base (NSBa) angle over time. The splanchnocranium, on the contrary,
      has undergone a dramatic involution, even conditioning gnathic structures with
      changes in palatal shape (more acute) and in the relationship between the jaws on
      the sagittal plane, resulting in increased prevalence of Angle's class I and III
      malocclusions.

PMID- 22580802
TI  - Endovascular treatment in postpartum haemorrhage.
AB  - PURPOSE: Postpartum haemorrhage (PPH) is one of the main causes of maternal
      mortality and occurs in 5% of total deliveries. In this study we consider the
      indications for and technique and results of endovascular treatment for this
      serious event. MATERIALS AND METHODS: Between January 2004 and December 2010, we
      conducted a nonrandomised prospective study on ten women with severe PPH who were
      treated endovascularly in an emergency setting. The procedure was considered to
      be clinically successful when the PPH resolved completely without the need for
      further surgical intervention. Laboratory values and the number of transfused
      blood packs were assessed for each patient. RESULTS: The endovascular procedure
      completely stopped the bleeding in 8/10 women. After embolisation, the remaining
      two patients underwent a second laparotomy, which completely arrested the
      bleeding. No patient died as a result of PPH, and no patient with PPH who avoided
      hysterectomy before endovascular treatment underwent it after the procedure.
      CONCLUSIONS: In keeping with the literature, our study indicates that
      endovascular therapy can significantly help reduce the rates of hysterectomy and
      mortality due to PPH. This treatment, when performed in the angiography room, is
      safe and effective and is probably relatively uncommon and underused.

PMID- 22580803
TI  - CT and MRI diagnosis of silent sinus syndrome.
AB  - PURPOSE: The purpose of this study was to determine computed tomography (CT) and
      magnetic resonance (MR) findings of silent sinus syndrome (SSS) - a rare clinical
      entity with the constellation of progressive enophthalmos and hypoglobus, facial
      asymmetry and possible diplopia - due to otherwise asymptomatic maxillary sinus
      disease. MATERIALS AND METHODS: We reviewed the pre- and postoperative CT and MR
      images of six patients with a definitive diagnosis of SSS and compared the
      radiological and clinical findings with those reported in the literature.
      RESULTS: The CT and MR studies demonstrated in all cases the most characteristic
      imaging features of SSS reported in the literature. CONCLUSIONS: Both CT and MR
      imaging enable a diagnosis of SSS to be made, but CT provides a better depiction
      of all features of SSS necessary for diagnosis and differentiation from other
      sinus conditions, even in patients without a clinical suspicion of SSS.

PMID- 22580804
TI  - Target registration errors with surface imaging system in conformal radiotherapy
      for prostate cancer: study on 19 patients.
AB  - PURPOSE: Accurate patient setup is a prerequisite for conformal radiotherapy (3D
      CRT) and is based on various methods, including surface imaging systems. To
      evaluate the validity of a surface imaging system (AlignRT), we analysed setup
      reproducibility of a cohort of patients. MATERIALS AND METHODS: Nineteen patients
      affected by prostate adenocarcinoma were enrolled in this study. We acquired 653
      surface images and 99 digital portal images (DPI). Setup errors were found by
      matching surface images with computed tomography (CT) and DPI images. RESULTS:
      The setup errors from the threshold of 5 mm detected by AlignRT along the Y, Z
      and X axes occurred in 47.4%, 42.1% and 5.3% of patients, respectively. For the
      threshold of 3 mm, shifts along the Y, Z and X axes were observed in 68%, 69% and
      10%, respectively. Comparing AlignRT and DPI, we found a statistically
      significant difference in the detection of shifts along the Y and Z axes. For a
      threshold >= 5 mm, the two systems provided corresponding setup errors along the
      Y and Z axes, whereas along the X axis, the threshold was not necessary.
      CONCLUSIONS: AlignRT is an accurate technique for setup in 3D-CRT prostate cancer
      patients, especially along the lateral direction.

PMID- 22580805
TI  - Violence against radiologists. II: Psychosocial factors.
AB  - PURPOSE: Violence against radiologists is a growing problem. This study evaluated
      the psychosocial factors associated with this phenomenon. MATERIALS AND METHODS:
      A questionnaire was administered to 992 Italian radiologists. RESULTS: Physical
      violence experienced in the previous 12-month period was associated with the
      radiologist's poor mental health [odds ratio (OR) 1.11] and overcommitment to
      work (OR 1.06), whereas radiologists in good physical health (OR 0.64), with job
      satisfaction (OR 0.96) and with overall happiness (OR 0.67) were less exposed.
      Nonphysical abuse was equally associated with the radiologist's poor mental
      health (OR 1.10) and overcommitment (OR 1.14) and negatively associated with
      physical health (OR 0.54), job satisfaction (OR 0.96), happiness (OR 0.81),
      organisational justice (OR 0.94) and social support (OR 0.80). CONCLUSIONS:
      Preventive intervention against violence in the workplace should improve
      workplace organisation and relationships between workers.

PMID- 22580806
TI  - Violence against radiologists. I: Prevalence and preventive measures.
AB  - PURPOSE: Violence in the workplace is a specific risk for healthcare workers.
      Radiologists, especially when involved in emergency services, share that risk.
      Very few studies in the literature have researched this topic. This study aimed
      to evaluate the prevalence of violent behaviour in a large sample of Italian
      radiologists and analyse the phenomenon and its consequences with a view to
      proposing preventive measures. MATERIALS AND METHODS: A total of 992 radiologists
      (61.5% men) taking part in a national radiology congress agreed to respond to a
      questionnaire on violence that contained the Violent Incident Form by Arnetz for
      the description of violent incidents in healthcare practice. RESULTS: Some 6.8%
      of radiologists in public hospitals experienced physical abuse in the previous 12
      months, for the most part from patients or their companions. The prevalence of
      physical abuse is greatest among younger healthcare individuals with less
      clinical experience, with no differences between sexes. Among younger
      radiologists, one in five suffered at least one act of physical abuse in a
      working year. Nonphysical violence is more widespread and throughout
      radiologists' working lives affects 65.2% of them. In this case, almost half of
      the violent incidents originate from colleagues. A total of 5.5% of respondents
      stated that they were victims of abuse at the time of the survey. In most cases,
      the violent incidents remain unreported. The immediate consequences of violence
      in the workplace are emotions such as anger, disappointment, humiliation,
      anxiety, fear, distress, a feeling of helplessness and isolation, occasionally a
      feeling of guilt or of having done wrong and a desire to take revenge, change
      behaviour or change workplace. CONCLUSIONS: The extent of the problem calls for
      the adoption of a series of measures aimed at eliminating the causes of the
      various forms of workplace violence.

PMID- 22580807
TI  - Emergency stent-graft implantation for iatrogenic peripheral arterial rupture.
AB  - PURPOSE: We evaluated the experience with and efficacy of stent-grafting for
      iatrogenic peripheral arterial ruptures. MATERIALS AND METHODS: From 2005 to 2009
      we performed stent-grafting on four male patients (age 38-67 years) with
      iatrogenic peripheral arterial ruptures. In patient 1, grointissue necrosis
      followed a subcutaneous injection and led to femoral arterial rupture.
      Pseudoaneurysms ruptured in patients 2 and 3 who were undergoing femoral
      arteriotomy. Patient 1 experienced a ruptured carotid artery during neck surgery.
      Shock occurred in three of the four patients. Four patients underwent self
      expanding stent-grafting (8 mm*60 mm or 8 mm*80 mm) under local anaesthesia.
      RESULTS: Haemorrhages were controlled in all patients. No procedure-related
      complications occurred. Patient 1 died of lung metastases 13 months after stent
      grafting. Follow-up examinations showed that the stent-graft remained patent in
      patients 1, 2 and 4, whereas stent occlusion occurred after 15 months in patient
      3; in this case, a pseudoaneurysm proximal to the stent was identified, and
      although repeat stent-grafting successfully stopped the bleeding, the patient
      died of multiple organ failure 1 week later. CONCLUSIONS: Emergency stent
      grafting is a technically feasible and therapeutically effective modality for
      treating high-risk patients who experience iatrogenic peripheral arterial
      ruptures. The efficient treatment of hypotension and early endovascular
      intervention will improve the prognosis.

PMID- 22580808
TI  - Follow-up in pulmonary sarcoidosis: comparison between HRCT and pulmonary
      function tests.
AB  - PURPOSE: The authors assessed the clinical usefulness of high-resolution computed
      tomography (HRCT) for monitoring sarcoidosis by comparing changes on HRCT with
      those on pulmonary function test (PFT) results over time. MATERIALS AND METHODS:
      The baseline and follow-up (after 13 months, range 15-63 months) HRCT scans of 14
      consecutive patients with sarcoidosis were reviewed by a single observer. Each
      follow-up HRCT examination was assessed as stable, improved (when the extent of
      HRCT findings was reduced compared with baseline) and worsened (when the extent
      of HRCT findings was increased and/or when HRCT pattern had become fibrotic
      compared with baseline). Any increase or decrease in forced vital capacity
      (FVC)>=10% from baseline was considered significant. Changes on HRCT were then
      compared with those on FVC. RESULTS: During a median follow-up of 33 (range 15
      63) months, HRCT findings worsened in 8/14 (58%) cases, improved in 3/14 (21%)
      and remained stable in 3/14 (21%). Agreement between changes on HRCT and FVC was
      moderate (kappa=0.49). In 9/14 (64%) cases, HRCT changes were in line with those
      on FVC. In 4/5 discordant cases, the worsened HRCT findings were not mirrored by
      FVC changes. CONCLUSIONS: Despite the small size of our study population, our
      results suggest that HRCT may provide clinicians with additional information
      about the evolution of sarcoidosis.

PMID- 22580809
TI  - Densitometric CT evaluation of acute and chronic thromboembolic filling defects
      of the pulmonary arteries before and after contrast injection.
AB  - PURPOSE: The aim of this study was to assess the baseline computed tomography
      (CT) attenuation of acute and chronic pulmonary thromboemboli, their contrast
      enhancement (CE), correlation with haematocrit (Ht) levels and the presence of
      hypertrophic bronchial arteries. MATERIALS AND METHODS: From January 2006 to
      October 2009, we measured the baseline and postcontrast attenuation values of
      acute pulmonary thrombi emboli on CT angiograms of 86 patients with acute
      pulmonary embolism (PE) and those of chronic thrombi in 29 patients with
      pulmonary hypertension of various origins. The attenuation of acute thrombi was
      correlated with Ht and CE of chronic thrombi with the presence of hypertrophic
      bronchial arteries. RESULTS: Acute emboli had a mean baseline attenuation of 54.9
      Hounsfield units (HU) and showed no CE. The attenuation of acute thrombi was not
      dependent on Ht. Chronic thrombi had a mean baseline attenuation of 33.8 HU, and
      54% of thrombi showed significant CE. In 57% of cases, a collateral circulation
      had developed. In 76.5% of cases, CE and hypertrophic bronchial arteries
      coexisted (p=0.026). Neither thrombotic CE nor bronchial artery hypertrophy
      predominated in any one of the diseases associated with chronic thrombosis.
      CONCLUSIONS: Before contrast administration, acute emboli coare prevalently
      hyperattenuating and therefore more conspicuous. Only chronic thrombi exhibit CE,
      and CE is significantly associated with the development of collateral
      circulation, which may be involved in the process of thrombotic recanalisation.

PMID- 22580810
TI  - Assessment of response to chemoradiation therapy in rectal cancer using MR
      volumetry based on diffusion-weighted data sets: a preliminary report.
AB  - PURPOSE: This study evaluated the feasibility of magnetic resonance (MR)
      volumetry using a diffusion-weighted data set (V(DWI)) and compared it with
      conventional T2-weighted volumetry (V(C)) in patients affected by rectal cancer
      treated with chemoradiation therapy (CHRT). MATERIALS AND METHODS: Fourteen
      patients with a biopsy diagnosis of rectal cancer underwent MR examination before
      and after CHRT. T2-weighted images were used to extrapolate V(C). A diffusion
      weighted (DW) sequence was acquired [spin-echo diffusion-weighted echo-planar
      imaging (SE-DW-EPI)] with a b-value of 800 s/mm(2) and volume (V(DWI)) was
      calculated by semiautomatic segmentation of tumour hyperintensity. Two
      radiologists independently assessed volumes and analysed data in order to
      establish interobserver agreement and compare and correlate volumes to tumour
      regression grade (TRG), as evaluable at pathological examination of the surgical
      specimen. RESULTS: Interobserver agreement was 0.977 [(95% confidence interval
      (CI) 0.954-0.989) and 0.956 (95% CI 0.905-0.980) for V(C) and V(DWI) and 0.964
      (95% CI 0.896-0.988) and 0.271 (95% CI-0.267 to 0.686) between V(C) and V(DWI)
      before and after CHRT. The correlation between TRG and V(C) and V(DWI) was,
      respectively, rho = 0.597 (p<0.05) and r(2)=0.156 (p=0.162) and rho=0.847
      (p<0.001). CONCLUSIONS: V(DWI) seems to be a promising tool for assessing
      response to CHRT in rectal cancer. Further studies on large series of patients
      are needed to refine the technique and evaluate its potential predictive value.

PMID- 22580811
TI  - Contrast-enhanced ultrasound evaluation of peripheral microcirculation in
      diabetic patients: effects of cigarette smoking.
AB  - PURPOSE: Cigarette smoking and diabetes mellitus predisposes to vascular disease.
      Our study aimed to evaluate the chronic effects of cigarette smoking on
      peripheral microcirculation assessed with contrast-enhanced ultrasound (CEUS) in
      diabetic patients. MATERIALS AND METHODS: The study population comprised ten
      smoker (7/3 M/W, age 42-76 years) and 16 nonsmoker (8/8 men/women, age 47-80
      years) diabetic patients. The ankle-brachial index (ABI) was determined, and
      colour Doppler ultrasound (CDUS) of the lower legs was performed to determine the
      presence of peripheral arteriopathy disease (PAD). Microvascular blood flow in
      the gastrocnemius muscle was evaluated with CEUS. RESULTS: No differences were
      observed in ABI and CDUS examination between smokers and nonsmokers. Smoking had
      a significant effect on microcirculatory function. Timeto-peak (TTP), arrival
      time in tissue (ATt) and artery/ tissue transit time (A/Ttt) were significantly
      prolonged in smokers (TTP 43.76 +/- 9.38 s vs. 34.12 +/- 6.8 s, p=0.011, ATt 28.9
      +/- 7.5s vs. 22.4 +/- 6.4 s, p=0.017 and A/Ttt 6.81 +/- 4.52 s vs. 3.25 +/- 3.27
      s, p=0.02), with no significant differences between patients with and without
      PAD. CONCLUSIONS: The long-term exposure to cigarette smoke affects
      microcirculatory function. Contrast imaging is a noninvasive technique that can
      document these effects.

PMID- 22580812
TI  - Diffusion tensor magnetic resonance imaging of the normal breast: reproducibility
      of DTI-derived fractional anisotropy and apparent diffusion coefficient at 3.0 T.
AB  - PURPOSE: Diffusion-weighted imaging (DWI) may improve the diagnostic performance
      of conventional breast magnetic resonance imaging (MRI). Diffusion tensor imaging
      (DTI) is an extension of DWI. If DTI-derived measurements are to be clinically
      useful, particularly for predicting and/or monitoring therapeutic effects, they
      must be robust and reliable. The purpose of this study was to assess intra- and
      interobserver reproducibility of DTI-derived fractional anisotropy (FA) and
      apparent diffusion coefficient (ADC) at 3.0 T. MATERIALS AND METHODS: This
      prospective study was approved by the Institutional Review Board, and
      participants provided written informed consent. Sixty normal contralateral
      breasts of 60 patients (28-85 years, median 57) were analysed with a DWI sequence
      following a standard MRI protocol. Four authors performed all postprocessing and
      analyses independently and in different sessions. The same authors, blinded to
      the initial results, repeated the image postprocessing and analysis 4 weeks after
      the initial session. RESULTS: Mean ADC and FA for DTI sequences were,
      respectively, 1.92+/-0.30 and 0.32+/-0.09. Intra- and interobserver agreement of
      the four radiologists for ADC and FA were good (acceptable). Kappa values for ADC
      were intra-R1=0.82; intra-R2=0.84; intra-R3=0.89; intra-R4=0.88; inter-R1
      R2=0.73; inter-R1-R3=0.74; inter-R1-R4=0.81; inter-R2-R3=0.76; inter-R2-R4=0.77;
      inter-R3-R4=0.83. Kappa values for FA were intra-R1=0.60; intra-R2=0.72; intra
      R3=0.84; intra-R4 = 0.66; inter-R1-R2=0.64; inter-R1-R3=0.69; inter-R1-R4=0.72;
      inter-R2-R3=0.80; inter-R2-R4=0.71; inter-R3-R4=0.73. Within-subject coefficient
      of variation was 15% for ADC and 30% for FA. Repeatability with alpha=0.05 was
      0.37*10-3 mm(2)/s for ADC and 0.112 for FA. CONCLUSIONS: ADC and FA measurements
      obtained with DTI are reproducible and may be valid, reliable and sensitive to
      change. ADC values obtained with DTI are more reproducible than FA.

PMID- 22580813
TI  - Role of diffusion-weighted magnetic resonance imaging in prostate cancer
      evaluation.
AB  - PURPOSE: The authors analysed the role of diffusion-weighted imaging (DWI) as an
      additional tool in magnetic resonance (MR) evaluation of prostate cancer.
      MATERIALS AND METHODS: Forty-one patients with suspected prostate cancer
      underwent MR imaging (1.5 Tesla). A DWI sequence was added to the standard
      morphological protocol, with a maximum b value of 1,000 s/mm(2). Diffusion maps
      were obtained, and the apparent diffusion coefficient (ADC) was calculated by
      drawing a region of interest (ROI) over healthy tissue and areas suspicious for
      malignancy. Histology was considered the gold standard. RESULTS: The areas
      correctly classified by MR imaging (42/51) had a low signal intensity on T2
      weighted imaging and low ADC value (0.99 +/- 0.15 mm(2)/s; p<0.01) compared with
      the healthy peripheral zone (PZ) (1.73 +/- 0.27 mm(2)/s; p<0.01). Nine areas
      classified as suspicious for malignancy on T2-weighted sequences showed high ADC
      (1.44 +/- 0.06 mm(2)/s; p<0.01) and were confirmed to be disease free by
      subsequent histological examination. The accuracy of morphofunctional MR imaging
      was 81.6% compared with 73.7% of the morphological analysis alone. CONCLUSIONS:
      The addition of DWI to the standard protocol increases the overall diagnostic
      performance of MR imaging in detecting prostatic cancer. Thus, DWI can help the
      clinician determine the most appropriate management strategy for the patient.

PMID- 22580814
TI  - External-beam radiotherapy and/or HDR brachytherapy in postoperative endometrial
      cancer patients: clinical outcomes and toxicity rates.
AB  - PURPOSE: The objectives of this study were to evaluate local disease control,
      overall survival (OS), disease-free survival (DFS) and local relapse-free
      survival (LRFS) in patients with endometrial cancer undergoing adjuvant vaginal
      brachytherapy (VBT )+/- external-beam radiotherapy (EBRT). MATERIALS AND METHODS:
      From September 2007 to February 2011, 40 patients with endometrial cancer were
      retrospectively analysed. Surgery consisted of total hysterectomy and bilateral
      salpingo-oophorectomy without node dissection (16 patients) or with bilateral
      pelvic node dissection (24 patients). The stage distribution was as follows: two
      IA, nine IB, 12 IC, five IIA, eight IIB, two IIIA and two IIIC. Thirty-four
      patients underwent EBRT and VBT. Six patients received VBT alone. RESULTS: Median
      follow-up was 26 months. The 5-year OS and DFS were 96.4% and 86.9%,
      respectively. No local recurrence was observed. Four patients presented distant
      disease (three had lung metastases and one had hepatic node metastases). Acute
      EBRT-related toxicities were seen in 15 (38%) patients. We recorded late
      toxicities in 14 patients (35%). There was no evidence of grade 3-4 toxicity.
      CONCLUSIONS: Adjuvant EBRT and/or VBT in patients with endometrial cancer showed
      good outcomes in terms of local disease control, with an acceptable toxicity
      profile.

PMID- 22580815
TI  - Rapid palliative radiotherapy unit: multidisciplinary management of bone
      metastases.
AB  - PURPOSE: The aim of this study was to highlight the advantages of rapid access to
      a palliative radiotherapy unit adopting a multidisciplinary approach to symptom
      management to relieve pain and improve quality of life in patients with bone
      metastases. MATERIALS AND METHODS: From January 2007 to December 2008, 142
      oncological patients were treated with linear accelerator radiotherapy (RT)
      administered in a single 8-Gy fraction. The European Organization for Research
      and Treatment Quality of Life Questionnaire (EORTC QLQ-C30) was administered to
      each patient at admission and at subsequent intervals. A traditional simulator
      was used to define the correct patient setup, and all treatment plans were
      performed with a two-dimensional technique.. RESULTS: Ninety-six patients agreed
      to fill in the EORTC QLQ-C30 questionnaire; 80 actually completed it. Twelve
      weeks after RT, a reduction in pain level compared with baseline (T0) was
      recorded, which was classified as 1 in 36 patients (45%) and 2 in 44 patients
      (55%). Pain interference with daily activities was also recorded, with
      significantly reduced scores with respect to T0: 1 in eight patients (10%), 2 in
      28 patients (35%) and 3 in 44 patients (55%); quality of life scores also
      improved with respect to T0: 2 in 28 patients (35%), 3 in 23 patients (29%), 4 in
      22 patients (27%) and 5 in seven patients (9%). CONCLUSIONS: The proposal for
      treating patients with painful bone metastases with a single 8-Gy fraction of RT,
      with all the procedures being performed on the same day, offers many advantages
      in terms of pain relief, quality of life and clinical management.

PMID- 22580816
TI  - Comorbidity assessment and adjuvant radiochemotherapy in elderly affected by
      glioblastoma.
AB  - To assess the role of comorbidity on outcome in elderly patients with
      glioblastoma treated with radiotherapy plus concomitant and adjuvant
      Temozolomide, patients over 65 years with glioblastoma, who underwent surgical
      resection or biopsy and radiochemotherapy, were evaluated. The Adjusted-Age
      Charlson Comorbidity Index and the Adult Comorbidity Evaluation-27 were used to
      assess comorbidity. From April 2005 to January 2011, 35 patients (median age 72
      years) were treated in our Institution. Thirteen patients had a Charlson score
      more than 3, while, according to the Adult Comorbidity Evaluation-27, 21 patients
      had mild or severe comorbid conditions. Patients with low Charlson comorbidity
      score experienced a longer survival time than those with higher score (22 vs. 10
      months, respectively). The Adjusted-Age Charlson Comorbidity Index influenced
      survival at univariate and multivariate analysis (p = 0.004, p = 0.001,
      respectively). No comorbidity index was a predictor for progression-free
      survival. Our data suggested that the association of radiotherapy with TMZ was
      safe and effective. Perhaps, the comorbidity assessment could be an appropriate
      tool in the treatment decision for elderly patients with glioblastoma.

PMID- 22580817
TI  - Prognostic value of tumor growth factor levels during chemotherapy in patients
      with metastatic colorectal cancer.
AB  - Tumor growth and angiogenic factors are usually overexpressed in colorectal
      carcinomas. We aimed to assess the prognostic role of VEGF, bFGF, PDGF-AA, EGF,
      HGF, and E-selectin in patients with metastatic colorectal cancer treated with
      capecitabine and oxaliplatin (XELOX) chemotherapy protocol. Thirty-eight
      colorectal cancer patients who had evidence of distant metastasis were enrolled
      in the study. Angiogenic factors were measured before and after third cycle of
      chemotherapy. Patients were randomized into three groups, partial response (PR),
      stable disease (SD), and progressive disease (PD) groups, according to their
      clinical and radiologic evaluation after three cycles of XELOX chemotherapy.
      Eighteen patients (47.3 %) achieved partial response, 10 (26.3 %) stable disease,
      and 10 (26.3 %) progressive disease. VEGF (63.20 Pg/ml vs. 19,79 Pg/ml; p <
      0.001), EGF (7.29 +/- 3.08 Pg/ml vs. 4.79 +/- 2.05 Pg/ml; p < 0.011), HGF (618.16
      +/- 340.39 Pg/ml vs. 452.02 +/- 217.18 Pg/ml; p < 0.049), and PDGF-AA (691.68 +/-
      187.10 Pg/ml vs. 404.89 +/- 168.47 Pg/ml; p < 0.001) were significantly decreased
      in PR group. PDGF-AA levels were also decreased in SD group (706.66 +/- 206.66
      Pg/ml vs. 389.79 +/- 143.16 Pg/ml; p < 0,001). HGF levels were significantly
      increased in PD disease group (449.99 Pg/ml vs. 682.22 Pg/ml; p < 0.046). The
      baseline E-selectin levels were inversely proportional with overall survival that
      could be an important prognostic factor at the time of diagnosis. This study
      demonstrated that tumor growth factors can be helpful to determine colorectal
      cancer prognosis and overall survival in patients with metastatic disease. VEGF,
      HGF, EGF, and PDGF-AA levels were decreased in PR group. However, meaningful
      increment was seen HGF levels in PD group. Angiogenic factors and E-selectin
      provided unique prognostic information in advanced colorectal carcinoma patients.

PMID- 22580818
TI  - Bone marrow-derived cells contribute to cell turnover in aging murine hearts.
AB  - The paradigm that cardiac myocytes are non-proliferating, terminally
      differentiated cells was recently challenged by studies reporting the ability of
      bone marrow-derived cells (BMCs) to differentiate into cardiomyocytes after
      myocardial damage. However, little knowledge exists about the role of BMCs in the
      heart during physiological aging. Twelve-week-old mice (n=36) were sublethally
      irradiated and bone marrow from littermates transgenic for enhanced green
      fluorescent protein (eGFP) was transplanted. After 4 weeks, 18 mice were
      sacrificed at the age of 4 months and served as controls (group A); the remaining
      mice were sacrificed at the age of 18 months (group B). Group A did not exhibit a
      significant number of eGFP+ cells, whereas 9.4+/-2.8 eGFP+ cells/mm2 was
      documented in group B. In total, only five eGFP+ cardiomyocytes were detected in
      20 examined hearts, excluding a functional role of BM differentiation in
      cardiomyocytes. Similarly, a relevant differentiation of BMCs in endothelial or
      smooth muscle cells was excluded. In contrast, numerous BM-derived fibroblasts
      and myofibroblasts were observed in group B, but none were detected in group  A.
      The present study demonstrates that BMCs transdifferentiate into fibroblasts and
      myofibroblasts in the aging murine myocardium, suggesting their contribution to
      the preservation of the structural integrity of the myocardium, while they do not
      account for regenerative processes of the heart.

PMID- 22580819
TI  - Regioselectivity of substrate hydroxylation versus halogenation by a nonheme
      iron(IV)-oxo complex: possibility of rearrangement pathways.
AB  - Several nonheme iron enzymes and biomimetic model complexes catalyze a substrate
      halogenation reaction. Recent computational studies (Borowski et al. J Am Chem
      Soc 132:12887-12898, 2010) on alpha-ketoglutarate dependent halogenase proposed
      an initial isomerization reaction that is important to give halogenated products.
      We present here a series of density functional theory calculations on a
      biomimetic model complex-[Fe(IV)(O)(TPA)Cl](+), where TPA is tris(2
      pyridylmethyl)amine-and investigate the mechanisms of substrate halogenation
      versus hydroxylation using the reactant and its isomer where the oxo and chloro
      groups have changed positions. We show here that the reactions occur on a
      dominant quintet spin state surface, although the reactants are in a triplet
      state. Despite the fact that the reactants can exist in two stable isomers with
      the oxo group either trans or cis to the axial ligand, they react differently
      with substrates, where one gives dominant hydroxylation and the other gives
      dominant chlorination of substrates. The ligand in the cis position of the oxo
      group is found to be active in the reaction mechanism and donated to the
      substrate during the reaction. A detailed thermochemical analysis of possible
      reaction mechanisms reveals that the strengths of the Fe-OH and Fe-Cl bonds in
      the radical intermediates are the key reasons for this regioselectivity switch of
      hydroxylation over halogenation. This study highlights the differences between
      enzymatic and biomimetic halogenases, where the former only react after an
      essential isomerization step, which is not necessary in model complexes.

PMID- 22580820
TI  - Effects of acupuncture on the gene expression profile of lung tissue from normal
      rats.
AB  - Acupuncture has been demonstrated to be an effective treatment for various
      diseases. However, little attention has been paid to its physiological
      influences, especially on the changes in protein and mRNA levels following
      acupuncture treatment under normal conditions. In this study, we investigated the
      gene expression profile of lung tissue from acupuncture-treated normal rats and
      attempted to characterize the underlying mechanisms of the changes in expression.
      Three common acupoints, Dazhui (GV14), fengmen (BL12) and feishu (BL13) were
      selected for analysis, and 2 serial analyses of gene expression (SAGE) tag
      libraries of the lung tissues that were derived from the normal and acupuncture
      treated rats were established. Bioinformatic analyses were carried out using the
      functional annotation tools of the database for annotation, visualization and
      integrated discovery (DAVID), the gene ontology (GO) Tree Machine and the Kyoto
      encyclopedia of genes and genomes (KEGG) pathway analysis. In total, 144 tags
      were differentially expressed (P<0.05), and the DAVID functional classification
      of genes demonstrated that the genes were divided into 6 types. Furthermore, GO
      Tree Machine analysis of the gene categories indicated that 10 enriched GO
      categories had become enriched after acupuncture, and that 15 KEGG pathways
      matched the differentially expressed tags of the 2 SAGE libraries. Our results
      show that the essential effects of acupuncture on normal rats include the
      regulation of macromolecular biosynthesis, transportation and metabolism.
      Cellular biosynthesis and cellular lipid metabolism are the common biological
      processes that occur in response to acupuncture under normal and morbid
      conditions, which may be the general physiological effects of acupuncture.

PMID- 22580821
TI  - The KDEL receptor couples to Galphaq/11 to activate Src kinases and regulate
      transport through the Golgi.
AB  - Membrane trafficking involves large fluxes of cargo and membrane across separate
      compartments. These fluxes must be regulated by control systems to maintain
      homoeostasis. While control systems for other key functions such as protein
      folding or the cell cycle are well known, the mechanisms that control secretory
      transport are poorly understood. We have previously described a signalling
      circuit operating at the Golgi complex that regulates intra-Golgi trafficking and
      is initiated by the KDEL receptor (KDEL-R), a protein previously known to mediate
      protein recycling from the Golgi to the endoplasmic reticulum (ER). Here, we
      investigated the KDEL-R signalling mechanism. We show that the KDEL-R is
      predicted to fold like a G-protein-coupled receptor (GPCR), and that it binds and
      activates the heterotrimeric signalling G-protein Galpha(q/11) which, in turn,
      regulates transport through the Golgi complex. These findings reveal an
      unexpected GPCR-like mode of action of the KDEL-R and shed light on a core
      molecular control mechanism of intra-Golgi traffic.

PMID- 22580822
TI  - DNA methylation in an intron of the IBM1 histone demethylase gene stabilizes
      chromatin modification patterns.
AB  - The stability of epigenetic patterns is critical for genome integrity and gene
      expression. This highly coordinated process involves interrelated positive and
      negative regulators that impact distinct epigenetic marks, including DNA
      methylation and dimethylation at histone H3 lysine 9 (H3K9me2). In Arabidopsis,
      mutations in the DNA methyltransferase MET1, which maintains CG methylation,
      result in aberrant patterns of other epigenetic marks, including ectopic non-CG
      methylation and the relocation of H3K9me2 from heterochromatin into gene-rich
      chromosome regions. Here, we show that the expression of the H3K9 demethylase
      IBM1 (increase in BONSAI methylation 1) requires DNA methylation. Surprisingly,
      the regulatory methylated region is contained in an unusually large intron that
      is conserved in IBM1 orthologues. The re-establishment of IBM1 expression in met1
      mutants restored the wild-type H3K9me2 nuclear patterns, non-CG DNA methylation
      and transcriptional patterns at selected loci, which included DNA demethylase
      genes. These results provide a mechanistic explanation for long-standing puzzling
      observations in met1 mutants and reveal yet another layer of control in the
      interplay between DNA methylation and histone modification, which stabilizes DNA
      methylation patterns at genes.

PMID- 22580823
TI  - 3'-processing and strand transfer catalysed by retroviral integrase in crystallo.
AB  - Retroviral integrase (IN) is responsible for two consecutive reactions, which
      lead to insertion of a viral DNA copy into a host cell chromosome. Initially, the
      enzyme removes di- or trinucleotides from viral DNA ends to expose 3'-hydroxyls
      attached to the invariant CA dinucleotides (3'-processing reaction). Second, it
      inserts the processed 3'-viral DNA ends into host chromosomal DNA (strand
      transfer). Herein, we report a crystal structure of prototype foamy virus IN
      bound to viral DNA prior to 3'-processing. Furthermore, taking advantage of its
      dependence on divalent metal ion cofactors, we were able to freeze trap the viral
      enzyme in its ground states containing all the components necessary for 3'
      processing or strand transfer. Our results shed light on the mechanics of
      retroviral DNA integration and explain why HIV IN strand transfer inhibitors are
      ineffective against the 3'-processing step of integration. The ground state
      structures moreover highlight a striking substrate mimicry utilized by the
      inhibitors in their binding to the IN active site and suggest ways to improve
      upon this clinically relevant class of small molecules.

PMID- 22580824
TI  - ARF6 GTPase protects the post-mitotic midbody from 14-3-3-mediated
      disintegration.
AB  - In cytokinesis, there is a lengthy interval between cleavage furrow ingression
      and abscission, during which the midbody microtubule bundle provides both
      structural support for a narrow intercellular bridge and a platform that
      orchestrates the biochemical preparations for abscission. It is currently unclear
      how the midbody structure is stably maintained during this period. Here, we
      report a novel role for the ADP-ribosylation factor 6 (ARF6) GTPase in the post
      mitotic stabilisation of midbody. Centralspindlin kinesin-6/RhoGAP complex, a
      midbody component critical for both the formation and function of the midbody,
      assembles in a sharp band at the centre of the structure in a manner antagonised
      by 14-3-3 protein. We show that ARF6 competes with 14-3-3 for binding to
      centralspindlin such that midbodies formed by centralspindlin mutants that can
      bind 14-3-3 but not ARF6 frequently collapse before abscission. These data
      indicate a novel mechanism for the regulation of midbody dynamics in which ARF6
      protects the compacted centralspindlin assembly from dissipation by 14-3-3.

PMID- 22580826
TI  - Intestinal stem cells: no longer immortal but ever so clever....
AB  - To maintain tissue homeostasis, stem cells must balance self-renewal with
      differentiation. In some stem cell lineages this process is 'hard-wired' by the
      asymmetric partitioning of determinants at division, such that one stem cell
      daughter always remains pluripotent and other differentiates. But in a dynamic
      tissue like the intestinal epithelium, which might need to repair itself
      following an infection or expand to digest the fall harvest, this balancing act
      requires more flexibility. Recent studies of intestinal stem cell (ISC) lineages
      in the fruit fly and mouse provide new insights into how this plasticity is
      achieved. The mechanisms in these two homologous but rather different organs have
      remarkable similarities, and so are likely relevant to how stem cell pools are
      controlled in organs other than the intestine.

PMID- 22580825
TI  - Notch and Mef2 synergize to promote proliferation and metastasis through JNK
      signal activation in Drosophila.
AB  - Genetic analyses in Drosophila revealed a synergy between Notch and the
      pleiotropic transcription factor Mef2 (myocyte enhancer factor 2), which
      profoundly influences proliferation and metastasis. We show that these
      hyperproliferative and invasive Drosophila phenotypes are attributed to
      upregulation of eiger, a member of the tumour necrosis factor superfamily of
      ligands, and the consequent activation of Jun N-terminal kinase signalling, which
      in turn triggers the expression of the invasive marker MMP1. Expression studies
      in human breast tumour samples demonstrate correlation between Notch and Mef2
      paralogues and support the notion that Notch-MEF2 synergy may be significant for
      modulating human mammary oncogenesis.

PMID- 22580827
TI  - NURDs are required for diversity.

PMID- 22580828
TI  - A MatP-divisome interaction coordinates chromosome segregation with cell division
      in E. coli.
AB  - Initiation of chromosome segregation in bacteria is achieved by proteins acting
      near the origin of replication. Here, we report that the precise choreography of
      the terminus region of the Escherichia coli chromosome is also tightly
      controlled. The segregation of the terminus (Ter) macrodomain (MD) involves the
      structuring factor MatP. We characterized that migration of the Ter MD from the
      new pole to mid-cell and its subsequent persistent localization at mid-cell
      relies on several processes. First, the replication of the Ter DNA is concomitant
      with its recruitment from the new pole to mid-cell in a sequential order
      correlated with the position on the genetic map. Second, using a strain carrying
      a linear chromosome with the Ter MD split in two parts, we show that replisomes
      are repositioned at mid-cell when replication of the Ter occurs. Third, we
      demonstrate that anchoring the Ter MD at mid-cell depends on the specific
      interaction of MatP with the division apparatus-associated protein ZapB. Our
      results reveal how segregation of the Ter MD is integrated in the cell-cycle
      control.

PMID- 22580829
TI  - Untangling the mysteries of maternal inheritance with polycomb.

PMID- 22580830
TI  - Homonymous hemimacular thinning:  a unique presentation of optic tract injury in
      neuromyelitis optica.
AB  - A 42-year-old African American woman with a 5-year history of neuromyelitis
      optica was found to have an incongruous homonymous hemianopia. Optical coherence
      tomography (OCT) showed corresponding left homonymous hemimacular thinning.
      Magnetic resonance imaging of the brain demonstrated a demyelinating lesion in
      the left optic tract (OT) just anterior to the lateral geniculate nucleus and
      diffusion tensor magnetic resonance tractography confirmed axonal fiber loss in
      the left OT. This case illustrates the complementary and confirmatory roles of
      visual field testing, macular OCT, and neuroimaging in an OT lesion, which caused
      selective hemimacular thinning through retrograde degeneration.

PMID- 22580831
TI  - Hypertrophic cardiomyopathy: role of current recommendations by the american
      heart association for infective endocarditis.
AB  - In the past decade, there has been evolution in the diagnosis, management, and
      long-term care of patients with infective endocarditis and its complications.
      This includes the relatively new but contentious prophylactic antibiotic regimen.
      However, these cases still continue to pose a challenge in the adult and
      pediatric populations. We present a case of a teenager with hypertrophic
      cardiomyopathy that had an atypical presentation of infective endocarditis.

PMID- 22580832
TI  - Synthesis and properties novel polyurethane-hexafluorobutyl methacrylate
      copolymers.
AB  - Novel physically crosslinked polyurethane-hexafluorobutyl methacrylate (PU-M)
      copolymers were prepared by the macroiniferter-controlled radical polymerization
      method. The chemical structures of the PU-M copolymers were characterized by FT
      IR, (1)H-NMR, GPC, DSC, and XPS. The self-assembly and surface properties of the
      PU-M copolymers have been investigated. The results revealed that PU-M copolymers
      have good hydrophobility, so the hydrophobility of polyurethane could be easily
      adjusted by controlling the content of the hydrophobic vinyl monomers. The
      mechanical evaluation shows that PU-M copolymers exhibit good mechanical
      properties. The effects of the fluorine content on the surface properties and
      self-assembly of the PU-M copolymers were investigated. The morphology of the PU
      M copolymers' self-assembly was observed by transmission electron microscopy
      (TEM) and scanning electron microscopy (SEM), and the mechanism of self-assembly
      was investigated. Antimicrobial property of the chlorinated PU-M copolymers
      against both Escherichia coli and Bacillus subtilis bacteria was examined and
      showed increase compared to that of pure polyurethane.

PMID- 22580833
TI  - The depression treatment cascade in primary care: a public health perspective.
AB  - Major depressive disorder (MDD) is common and costly. Primary care remains a
      major access point for depression treatment, yet the successful clinical
      resolution of depression in primary care is uncommon. The clinical response to
      depression suffers from a "treatment cascade": the affected individual must
      access health care, be recognized clinically, initiate treatment, receive
      adequate treatment, and respond to treatment. Major gaps currently exist in
      primary care at each step along this treatment continuum. We estimate that 12.5%
      of primary care patients have had MDD in the past year; of those with MDD, 47%
      are recognized clinically, 24% receive any treatment, 9% receive adequate
      treatment, and 6% achieve remission. Simulations suggest that only by targeting
      multiple steps along the depression treatment continuum (e.g. routine screening
      combined with collaborative care models to support initiation and maintenance of
      evidence-based depression treatment) can overall remission rates for primary care
      patients be substantially improved.

PMID- 22580834
TI  - Cross-cultural aspects of depression management in primary care.
AB  - Major depressive disorder (MDD) is a prevalent illness in minority populations.
      Minority patients with MDD are often unrecognized and untreated. This review
      examines promising interventions to address MDD in primary care settings, where
      minority groups are more likely to seek care. Since 2010, eleven interventions
      have been developed to address patient-specific and provider-specific barriers,
      many of which are adaptations of the collaborative care model. Other promising
      interventions include cultural tailoring of the collaborative care model, as well
      as the addition of telepsychiatry, motivational interviewing, cultural
      consultation, and innovations in interpreting. Overall, collaborative care was
      found feasible and improved satisfaction and treatment engagement of depressed
      minority patients in primary care. It remains inconclusive whether these newer
      intervention models improve MDD treatment outcomes. Future research will be
      needed to establish the effectiveness of these intervention models in improving
      the treatment outcomes of minority populations with MDD.

PMID- 22580836
TI  - [Colorectal cancer: new challenges for radiologists].

PMID- 22580835
TI  - From genome-wide association studies to disease mechanisms: celiac disease as a
      model for autoimmune diseases.
AB  - Celiac disease is characterized by a chronic inflammatory reaction in the
      intestine and is triggered by gluten, a constituent derived from grains which is
      present in the common daily diet in the Western world. Despite decades of
      research, the mechanisms behind celiac disease etiology are still not fully
      understood, although it is clear that both genetic and environmental factors are
      involved. To improve the understanding of the disease, the genetic component has
      been extensively studied by genome-wide association studies. These have uncovered
      a wealth of information that still needs further investigation to clarify its
      importance. In this review, we summarize and discuss the results of the genetic
      studies in celiac disease, focusing on the "non-HLA" genes. We also present novel
      approaches to identifying the causal variants in complex susceptibility loci and
      disease mechanisms.

PMID- 22580837
TI  - [Magnetic resonance-guided high intensity focused ultrasound (MR-HIFU). The all
      round therapy of the future?].

PMID- 22580838
TI  - Contactin 1 (CNTN1) expression associates with regional lymph node metastasis and
      is a novel predictor of prognosis in patients with oral squamous cell carcinoma.
AB  - The contactin 1 (CNTN1) gene exerts oncogene-like activities and its expression
      has been linked to several human malignancies. In this study, a possible
      association between CNTN1 expression and clinicopathological parameters and
      clinical outcomes in patients with oral squamous cell carcinoma (OSCC) was
      examined. CNTN1 protein expression was evaluated by immunohistochemistry in OSCC
      tissues of 45 patients. For the immunohistochemical assessment of CNTN1
      expression, the cytoplasmic staining labeling index was analyzed using a
      semiquantitative score. The association between CNTN1 protein levels and
      clinicopathological factors was analyzed using the Mann-Whitney U test for
      categorical variables and the Kruskal-Wallis test for continuous variables. The
      effects of CNTN1 expression on overall and disease-free survival were assessed by
      using univariate survival analysis. The transcript levels of CNTN1 were detected
      in OSCC cell lines. In addition, specific siRNA against CNTN1 was applied to
      investigate the effect exerted by CNTN1 ablation on OSCC cell lines by
      proliferation and invasion assays in vitro. During follow-up, 16 patients
      (35.56%) had succumbed to OSCC; the median follow-up of patients was 5.0 years
      (range, 0.2-8.3). A high expression of CNTN1 was markedly associated with the
      regional lymph node metastasis of patients with OSCC (P=0.006). CNTN1 expression
      was significantly associated with overall survival of patients with OSCC
      (P=0.032; log-rank test) and disease-free survival of patients with OSCC
      (P=0.038; log-rank test). In addition, CNTN1 ablation notably suppressed the
      invasion potential of OSCC cell lines, but there was no significant change in the
      proliferation of OSCC cell lines by CNTN1 knockdown in vitro. The study supports
      CNTN1 as a novel predictor of regional lymph node metastasis in patients with
      OSCC and a prognostic marker for OSCC in patients.

PMID- 22580839
TI  - Frey procedure in patients with chronic pancreatitis: short and long-term outcome
      from a prospective study.
AB  - BACKGROUND: The aim of this prospective study was to determine the short- and
      long-term results of the Frey procedure in the treatment of chronic pancreatitis.
      METHODS: From September 2000 to November 2009, 44 consecutive patients underwent
      the Frey procedure. Patients were included in the study before surgery and
      followed prospectively with assessment of pain relief, weight gain and
      exocrine/endocrine insufficiency. Twenty-one patients (47.7%) were followed for
      more than 5 years. RESULTS: This study included 40 men (91 %) and four women (9
      %) (mean age: 49 years) with a mean follow-up of 51.5 months. The primary
      etiology of chronic pancreatitis was chronic alcohol abuse in 38 patients (86.4
      %). The major indication for surgery was disabling pain (95.5 %). There was no
      postoperative mortality. Postoperative morbidity occurred in 15 patients (34.1
      %), with specific surgical complications in 11 patients (25 %). The percentage of
      pain-free patients after surgery was 68.3 %. Eight patients (18.1 %) and seven
      patients (16 %) developed diabetes de novo and exocrine insufficiency,
      respectively. The Body Mass Index showed statistically significant improvement
      during follow-up. Similar beneficial results concerning pain relief and weight
      gain persisted after the initial 5-year follow-up. CONCLUSIONS: The Frey
      procedure is an appropriate, safe and effective technique for management of
      patients with chronic pancreatitis in the absence of neoplasia, based on long
      term follow-up.

PMID- 22580840
TI  - Antimesenteric functional end-to-end handsewn (Kono-S) anastomosis.
AB  - INTRODUCTION: Anastomotic recurrence is a frequent event after bowel resection
      for Crohn's disease. To date, no anastomotic technique has been proven to be
      superior in reducing surgical recurrence rates in this setting. In this article,
      we describe our technique in performing a new antimesenteric functional end-to
      end handsewn (Kono-S) anastomosis. METHODS: The segment of bowel to be resected
      is identified and mobilized. The bowel is then divided transversely with a linear
      stapler-cutter device. The intervening mesentery is divided close to the bowel.
      The corners of the two stapled lines are sutured together, and the two stapled
      lines are approximated with interrupted sutures. An antimesenteric longitudinal
      enterotomy is performed on both sides, starting no more than 1 cm away from the
      staple line, to allow a transverse lumen of 7-8 cm. The openings are closed
      transversely in two layers. RESULTS: From May 1, 2010 to July 31, 2011 we
      performed 46 Kono-S anastomoses. One patient had a contained anastomotic leak
      successfully treated conservatively. Currently, 18 patients (43 %) have undergone
      follow-up endoscopic surveillance with an average Rutgeert's score of 0.7 (0-3)
      at a mean of 6.8 months. CONCLUSION: The Kono-S anastomosis is a safe anastomotic
      technique. Long-term studies are needed to confirm its efficacy in preventing
      surgical recurrence.

PMID- 22580841
TI  - Single-incision laparoscopic cholecystectomy vs. conventional laparoscopic
      cholecystectomy: a meta-analysis of randomized controlled trials.
AB  - INTRODUCTION: We analyzed different morbidity parameters between single-incision
      laparoscopic cholecystectomy (SILC) and conventional laparoscopic cholecystectomy
      (CLC). METHODS: Pubmed, Ovid, Embase, SCI database, Cochrane, and Google Scholar
      were searched. The primary endpoints analyzed were cosmetic result and the
      postoperative pain (at 6 and 24 h) and the secondary endpoints were operating
      time, hospital stay, incidence of overall postoperative complications, wound
      related complications, and port-site hernia. RESULTS: Six hundred fifty-nine
      patients (SILC-349, CLC-310) were analyzed from nine randomized controlled
      trials. The objective postoperative pain scores at 6 and 24 h and the hospital
      stay were similar in both groups. The total postoperative complications, wound
      related problems, and port-site hernia formation, though higher in SILC, were
      also comparable in both groups. SILC had significantly favorable cosmetic scoring
      compared to CLC [weighted mean difference = 1.0, p = 0.0001]. The operating time
      was significantly longer in SILC [weighted mean difference = 15.63, p = 0.0001].
      CONCLUSIONS: Single-incision laparoscopic cholecystectomy does not confer any
      benefit in postoperative pain (6 and 24 h) and hospital stay as compared to
      conventional laparoscopic cholecystectomy while having significantly better
      cosmetic results at the same time. Postoperative complications, though higher in
      SILC, were statistically similar in both the groups.

PMID- 22580843
TI  - "Venous cut-off sign" as an adjunct to the "whirl sign" in recognizing acute
      small bowel volvulus via CT scan.
AB  - INTRODUCTION: A young adult patient was admitted for signs and symptoms of acute
      abdomen. MATERIALS AND METHODS: Urgent CT scan was performed and small bowel
      volvulus was confirmed. The "whirl sign" diagnostic of small bowel volvulus was
      present. RESULTS: Furthermore, the accompanying superior mesenteric vein was
      noted to be truncated at the point of torsion. CONCLUSION: The "venous cut-off
      sign" can be a useful adjunct sign to the diagnosis.

PMID- 22580842
TI  - Topically applied 2-octyl cyanoacrylate (Dermabond) for prevention of
      postoperative pancreatic fistula after pancreaticoduodenectomy.
AB  - OBJECTIVE: We examined whether 2-octyl cyanoacrylate (Dermabond) topically
      applied to the pancreaticojejunostomy (PJ) anastomotic site after
      pancreaticoduodenectomy (PD) reduces the rate of postoperative pancreatic fistula
      (POPF). METHODS: Patients who underwent PD with duct-to-mucosa PJ were evaluated
      (n = 124). Outcome was compared between patients who received Dermabond (n = 75)
      after PD and historic patients who did not (n = 49). Risk factors for POPF were
      identified. RESULTS: Overall and clinically relevant rates of POPF were
      significantly lower in patients who received Dermabond than in patients who did
      not (2.6 % and 1.3 % vs. 22 % and 12 %, respectively; p = 0.001). In univariate
      analysis, pancreatic duct diameter <=3 mm, low serum albumin level, and no
      Dermabond were independent risk factors for POPF; in multivariate analysis, no
      Dermabond was an independent risk factor for POPF. In patients with pancreatic
      duct diameter <=3 mm, the rate of POPF was significantly lower in patients who
      received Dermabond than in patients who did not (3.5 % versus 36 %, respectively;
      p = 0.0001). Patients who received Dermabond had significantly shorter hospital
      stays and lower re-operation and re-admission rates. CONCLUSIONS: Topical
      application of Dermabond to the PJ anastomotic site after PD significantly
      reduced the rate of POPF, particularly in patients at risk.

PMID- 22580844
TI  - Should cognition be screened in new-onset epilepsies? A study in 247 untreated
      patients.
AB  - The aim of our study was to assess cognition in newly diagnosed and untreated
      patients with epilepsy in order to determine the prevalence and the determinants
      of cognitive deficits at this early stage of the disease. A total of 247
      untreated patients with newly diagnosed epilepsy underwent a brief test battery
      focusing on attention and executive functions (EpiTrack((r))) and memory (short
      form of the VLMT). In addition, the assessment included ratings of self-perceived
      deficits in attention and memory. Impairments in attention and executive
      functions were seen in 49.4 % of the patients and memory deficits in 47.8 %.
      Unimpaired performance in both domains was observed in 27.9 % of the cases. Self
      perceived deficits in attention were only reported by 28.7 % of the patients, and
      25.1 % of the patients complained of memory impairments. Lower education and a
      symptomatic, i.e., lesional, cause of epilepsy were associated with worse
      performance in attention and executive functions, whereas worse memory
      performance was related to generalized tonic-clonic seizures. Results indicate a
      high prevalence of cognitive deficits at an early stage of epilepsy, which calls
      for consideration in the daily clinical care. Patients appear to underreport
      cognitive deficits. Thus, a routine application of a brief standardized
      neuropsychological screening before the initiation of a pharmacological treatment
      would be appreciated to provide a baseline to evaluate subsequent treatment
      success, to eventually initiate countermeasures, and to monitor the course of the
      disease.

PMID- 22580845
TI  - Sporadic transthyretin amyloidosis with a novel TTR gene mutation misdiagnosed as
      primary amyloidosis.

PMID- 22580846
TI  - POLG and PEO1 (Twinkle) mutations are infrequent in PSP-like atypical
      parkinsonism: a preliminary screening study.

PMID- 22580847
TI  - A series of novel lanthanide carboxyphosphonates with a 3D framework structure:
      synthesis, structure, and luminescent and magnetic properties.
AB  - By introduction of 1,4-benzenedicarboxylic acid as the second organic ligand, a
      series of novel lanthanide carboxyphosphonates with a 3D framework structure,
      namely, [Ln(3)(H(2)L)(HL)(2)(bdc)(2)(H(2)O)].7H(2)O (Ln = La (1), Ce (2), Pr (3),
      Nd (4), Sm (5), Eu (6), Gd (7), Tb (8); H(3)L = H(2)O(3)PCH(2)NC(5)H(9)COOH;
      H(2)bdc = HOOCC(6)H(4)COOH) have been synthesized under hydrothermal conditions.
      Compounds are isostructural and feature a 3D framework in which Ln(III) polyhedra
      are interconnected by bridging {CPO(3)} tetrahedra into 2D inorganic layers
      parallel to the ab plane. The organic groups of H(2)L(-) are grafted on the two
      sides of the layer. These layers are further cross-linked by the bdc(2-) ligands
      from one layer to the Ln atoms from the other into a pillared-layered
      architecture with one-dimensional channel system along the a axis. The thermal
      stability of compounds has been investigated. Luminescent properties of compounds
      , and the magnetic properties of compound have also been studied.

PMID- 22580848
TI  - Clastogenicity of landfarming soil treated with sugar cane vinasse.
AB  - The addition of nutrients and/or soil bulking agents is used in bioremediation to
      increase microbial activity in contaminated soils. For this purpose, some studies
      have assessed the effectiveness of vinasse in the bioremediation of soils
      contaminated with petroleum waste. The present study was aimed at investigating
      the clastogenic/aneugenic potential of landfarming soil from a petroleum refinery
      before and after addition of sugar cane vinasse using the Allium cepa bioassay.
      Our results show that the addition of sugar cane vinasse to landfarming soil
      potentiates the clastogenic effects of the latter probably due the release of
      metals that were previously adsorbed into the organic matter. These metals may
      have interacted synergistically with petroleum hydrocarbons present in the
      landfarming soil treated with sugar cane vinasse. We recommend further tests to
      monitor the effects of sugar cane vinasse on soils contaminated with organic
      wastes.

PMID- 22580849
TI  - Context memory in Korsakoff's syndrome.
AB  - Memory for contextual information and target-context integration are crucial for
      successful episodic memory formation and are impaired in patients with
      Korsakoff's syndrome. In this paper we review the evidence for the notion that a
      context memory deficit makes an important contribution to the amnesia in these
      patients. First, we focus on anterograde memory for contextual (spatial and
      temporal) information. Next, the use of contextual cues in memory retrieval is
      examined and their role in retrograde amnesia and confabulation. Evidence on the
      role of contextual cues and associations in working memory is discussed in
      relation to the underlying neurocognitive mechanisms and their dissociation from
      long-term encoding. Finally, we focus on implicit learning of contextual
      information in Korsakoff patients. It can be concluded that Korsakoff patients
      are impaired in the explicit processing of contextual information and in target
      context binding, both in long-term (retrograde and anterograde) memory and in
      working memory. These results extend the context memory deficit hypothesis. In
      contrast, implicit contextual learning is relatively preserved in these patients.
      These findings are discussed in relation to evidence of dysfunction of the
      extended diencephalic-hippocampal memory circuit in Korsakoff's syndrome.

PMID- 22580850
TI  - Transfection efficiency along the regenerating soleus muscle of the rat.
AB  - We investigated the efficiency of a single plasmid transfection along the
      longitudinal axis of the regenerating soleus of young rats. This also reflected
      transfection efficiency along the fibers because the soleus is a nearly fusiform
      muscle in young animals. The complete regeneration was induced by notexin and the
      transfection was made by intramuscular injection of enhanced green fluorescent
      protein- or Discosoma red-coding plasmids after 4 days. One week after
      transfection the number of transfected fibers was higher at the place of
      injection (i.e., in the muscle belly) and lower or absent at the ends of the
      muscle. The inspection of longitudinal sections and neuromuscular endplates
      indicated that one of the reasons of uneven transfection might be the shortness
      of transfected myotubes and the other reason might be the limit of diffusion of
      transgenic proteins from the expressing nuclei. As a result, the efficiency of
      transfection in the whole regenerating muscle was much lower than it could be
      estimated from the most successfully transfected part.

PMID- 22580851
TI  - Use of intramedullary fully-threaded pins in the fixation of feline and canine
      humeral, femoral and tibial fractures.
AB  - Intramedullary fully-threaded pins were manufactured from an alloy of titanium,
      aluminium and vanadium in a fully-threaded style. Pins were produced in various
      diameters, ranging from 4 mm to 11 mm. Pin lengths varied from 5 cm to 22 cm. The
      proximal end of the pins was designed to fit into a hexagonal screwdriver, while
      the distal end was slightly tapered to allow for ease of entry into cancellous
      bone. Treatment using the fully-threaded intra- medullary pin was carried out in
      a total of 175 fractures of the humerus, femur, and tibia in 95 cats (bilateral
      femur in 1 case) and 77 dogs (bilateral femur in 2 cases). Radiographic follow-up
      for the cases was performed at monthly intervals. Non-union developed in one dog
      with a femoral fracture in which cerclage wire had also been used. Delayed
      healing and lameness were observed in two other dogs. Healing with excessive
      callus formation was observed in 16 dogs. However, there were not any problems
      noted in these dogs in regards to limb usage. Clinical and radiological results
      obtained for the remaining cases were found to be very good. Normal, complete
      fracture healing occurred between four to 14 weeks in dogs, and between four to
      12 weeks in cats. Pins were removed upon observation of satisfactory functional
      and radiographic recovery. Pins could not be removed from 26 cats and 21 dogs as
      the owners had declined pin removal, or because the owners were lost to follow
      up.

PMID- 22580852
TI  - Disseminated tumor cells in bone marrow and the natural course of resected
      esophageal cancer.
AB  - OBJECTIVE: To assess the impact of disseminated tumor cells (DTC) in bone marrow
      on recurrence and survival in complete resected esophageal cancer (EC).
      BACKGROUND: Current modalities to predict tumor recurrence and survival in EC are
      insufficient. Here, we evaluated in a prospective study the prognostic relevance
      of DTC in bone marrow for the natural postoperative course of EC. METHODS: We
      enrolled 370 consecutive EC patients (1995-2009). All tumors, 189 squamous cell
      carcinomas and 181 adenocarcinomas, were completely surgically resected (R0), and
      patients received neither neoadjuvant nor adjuvant therapy. Disseminated tumor
      cells were detected by an immunocytochemical cytokeratin assay in preoperatively
      taken bone marrow aspirates. The results were correlated with clinic-pathological
      parameters and clinical outcome. RESULTS: Overall 120 (32.4%) patients harbored
      DTC in their bone marrow. Presence of DTC significantly correlated with
      aggressive tumor biology as indicated by increased tumor size (P = 0.026),
      regional (P = 0.002) and distant (P = 0.012) lymph node metastases, and higher
      relapse rate (P < 0.001, chi test). A gradual decrease in disease-free (P <
      0.001) and overall (P < 0.001, log-rank test) survival was observed between DTC
      negative and DTC-positive patients and was evident in subgroup analysis
      stratified for nodal status, lymph node yield, lymph node ratio, and tumor
      subtypes. Disseminated tumor cells were identified as a strong independent
      prognosticator of tumor recurrence (hazard ratio [HR] 4.0, 95% confidence
      interval [CI]: 2.96-5.45, P < 0.001) and overall survival (HR 3.1, 95% CI: 2.37
      4.09, P < 0.001, Cox regression analysis). CONCLUSIONS: The presence of DTC in
      bone marrow is a strong and independent prognostic factor in patients with
      resectable EC.

PMID- 22580854
TI  - BLIMP1alpha, the master regulator of plasma cell differentiation is a tumor
      supressor gene in B cell lymphomas.
AB  - AIMS: The aim of this review was to summarize recent knowledge of the structure
      and function of a transcriptional repressor, B lymphocyte induced maturation
      protein 1 (BLIMP1) and its participation in the pathogenesis of B lymphomas.
      METHODS AND RESULTS: This review summarizes the structure and function of BLIMP1,
      its major target genes and its role as a tumour suppressor in B cell lymphomas.
      We review our recent data implicating the loss of BLIMP1alpha as an important
      step in the pathogenesis of the Epstein-Barr virus (EBV) associated B cell
      lymphomas. CONCLUSIONS: BLIMP1 is a transcriptional repressor essential for the
      differentiation of germinal centre (GC) B cells to plasma cells. The loss of
      BLIMP1 in GC B cells could contribute to the pathogenesis of EBV-associated
      lymphomas by preventing plasma cell differentiation and viral replication.

PMID- 22580855
TI  - The in vitro antimicrobial activity of silicone oils used in ophthalmic surgery.
AB  - BACKGROUND: The aim of the study was in vitro assessment and comparison of the
      antimicrobial activity of three types of silicone oils used in ophthalmic
      surgery. METHODS: The silicone oils (Arciolane 1300 centistokes, Arciolane 5500
      centistokes and Oxane Hd, heavy silicone oil) were inoculated with microbes
      common in endophthalmitis and their growth was observed continuously. Control
      tests of microbial growth were performed on silicone oil-free media, i.e. saline
      and standard enrichment media. In both tested oils and control media, the
      microbes were cultured aerobically for 21 days, bacteria at 37  degrees C and
      yeasts and fungi at 30  degrees C. Prior to and during incubation at given
      intervals (days 0, 2, 4, 7, 9, 11, 14, 16, 18 and 21), 10 MUl samples were taken
      from all test tubes. These were diluted in saline in a series of test tubes, with
      the minimum concentration reaching 10(-8). From each dilution, 25 MUl were
      inoculated onto agar media. After 24 h of aerobic incubation at 37  degrees C
      (bacteria) and 48 h at 30  degrees C (yeasts and fungi), the grown colonies were
      counted and the numbers of colony-forming units in 1 ml (CFU/ml) were determined.
      RESULTS: In vitro, the highest antimicrobial effect was observed for the Oxane Hd
      silicone oil. CONCLUSIONS: If endophthalmitis is treated by pars plana
      vitrectomy, the application of Oxane Hd silicone oil into the vitreous cavity at
      the end of surgery may contribute to the elimination of microorganisms from the
      intraocular space but clinical trials are needed to assess its safety.

PMID- 22580856
TI  - In vivo oxidized low-density lipoprotein (ox-LDL) aopp and tas after kidney
      transplantation: a prospective, randomized one year study comparing cyclosporine
      A and tacrolimus based regiments.
AB  - AIMS: Restoration of renal function after kidney transplantation (KT) is expected
      to improve oxidative stress (OS). However, little is known about the influence of
      calcineurin inhibitors on oxidized low-density lipoproteins (ox-LDL) after KT.
      The aim of this study was to evaluate ox-LDLs and related markers of OS, advanced
      oxidation protein products (AOPP) and total antioxidant status (TAS) in patients
      after KT on either cyclosporin A (CyA) or tacrolimus (Tac) treatment. METHODS:
      This was a prospective, randomized, single-center 12 month study evaluating time
      dependent changes in biomarkers of OS before and after KT. Twenty nine patients
      (mean age 54.4 +/- 11.1; 55% male and 45% female) were treated with CyA (Group A)
      and twenty four patients (mean age 52.9 +/- 9.9; 75% male and 25% female) were
      treated with Tac (Group B). The ox-LDL, AOPP, TAS, lipid metabolism parameters,
      creatinine and glomerular filtration were assessed on day 1 before KT and on days
      1 and 7, and in months 1, 3, 6 and 12 after KT. RESULTS: Over the 12 months, the
      ox-LDL for group A changed from 69.2+/-32.9 to 65.1+/-17.1 U/L (P=0.665), while
      AOPP significantly decreased from 233.0+/-159.6 to 156.5+/-90.1 MUmol/L (P=0.025)
      and TAS from 1.87+/-0.31 to 1.68+/-0.20 mmol/L (P=0.030). For group B the ox-LDL
      changed from 62.9+/-29.7 to +/- 61.4+/-14.6 U/L (P=0.168) and TAS from 1.87+/
      0.51 to 1.68+/-0.20 mmol/L (P=0.168), while AOPP significantly decreased from
      180.5+/-90.0 to 123.9+/-37.7 MUmol/L (P=0.019). CONCLUSION: AOPP is more
      sensitive than ox-LDL for assessing OS after KT. TAS values appear to be
      insufficiently sensitive for monitoring OS in patients after KT.

PMID- 22580857
TI  - Gender differences in total cholesterol levels in patients with acute heart
      failure and its importance for short and long time prognosis.
AB  - AIM: The purpose of this study was to evaluate whether there are gender
      differences in total cholesterol levels in patients with acute heart failure and
      if there is an association of this parameter with short and long time mortality.
      METHODS: The AHEAD MAIN registry is a database conducted in 7 university
      hospitals, all with 24 h cath lab service, in 4 cities in the Czech Republic. The
      database included 4 153 patients hospitalised for acute heart failure in the
      period 2006-2009. 2 384 patients had a complete record of their total cholesterol
      levels. 946 females and 1437 males were included in this analysis. According to
      the admission total cholesterol levels, patients were divided into 5 groups: <
      4.50 mmol/l (group A), 4.50-4.99 mmol/l (group B), 5.0-5.49 mmol/l (group C),
      5.50-5.99 mmol/l (group D) and > 6.0 mmol/l (group E). The median total
      cholesterol levels were 4.24 in males and 4.60 in females (P<0.001). There were
      differences in the distribution of total cholesterol levels between men and
      women: group A 57.6 vs 45.0%, group B 13.8 vs 16.3%, group C 9.8 vs 12.5%, group
      D 7.7 vs 11.4%, group E 11.1 vs 14.8% respectively (all P<0.001). The median age
      of men was 68.7 vs 77.3 years in women (P<0.001). In all total cholesterol
      categories women were older than men: group A 77.7 vs 69.5 years, group B 78.6 vs
      69.1 years, group C 77.3 vs 68.8 years, group D 76.8 vs 64.2 years, group E 75.6
      vs 64.4 years (all P<0.001). For the calculation of long term mortality, the
      cohort was divided into three groups: total cholesterol levels below 4.50 mmol/l,
      4.50-5.49 mmol/l and above 5.50 mmol/l. The log rank test was used for the
      analysis. RESULTS: There were no differences in hospital mortality between male
      and female in general (9.2 vs 10.8%, P<0.202), or in total cholesterol levels in
      subgroups. Total cholesterol levels were associated with in-hospital mortality
      (P<0.002). In the long-term follow up (78 months) patients with total cholesterol
      levels below 4.5 mmol/l had the worst prognosis (P<0.001). An independent
      influence of total cholesterol level on mortality and survival was confirmed in
      the multivariate model as well. CONCLUSIONS: Women with acute heart failure had
      higher total cholesterol levels than men in all ages. There was a higher
      percentage of women with total cholesterol levels above 6 mmol/l and lower
      percentage in the group below 4.5 mmol/l than in men. In all, total cholesterol
      categories women were older than men. Total cholesterol levels are important for
      in- hospital mortality and long term survival of patients admitted for acute
      heart failure.

PMID- 22580858
TI  - Experience with the systemic treatment of severe forms of psoriasis.
AB  - INTRODUCTION: Severe forms of psoriasis are indicated for systemic treatment with
      conventional and biological preparations. The former includes methotrexate,
      cyclosporin, acitretin and narrow-band ultraviolet B phototherapy but toxicity
      may limit the dose and duration of treatment. Currently used less toxic
      biological preparations include inhibitors of TNF-alpha (etanercept, adalimumab,
      infliximab) and the monoclonal antibody against IL 12/23 ustekinumab. We present
      our own more than five-year experience with the systemic treatment of severe
      forms of psoriasis using these preparations. METHODS: A total of 66 patients
      treated with systemic therapy (except for phototherapy) were divided into groups
      based on treatment. Therapeutic doses were administered according to the
      recommendations of the manufacturer and dermatological societies. Standard PASI
      and BSA indexes were used to evaluate clinical condition at weeks 0, 12 and 24.
      RESULTS: Differences in PASI score reduction and BSA index between patient groups
      treated with different preparations were statistically significant at monitored
      intervals. At week 12, PASI score was reduced by 75% or more in a significantly
      greater number of patients treated with infliximab + methotrexate than those
      treated with acitretin. At week 24, identical comparison showed a significantly
      greater number of patients treated with etanercept or adalimumab than those
      receiving methotrexate. For BSA index reduction by 50% or more, no statistically
      significant differences were found between patient groups during the follow-up
      period. CONCLUSION: Systemic therapy provides a significant benefit to patients
      with severe psoriasis. Biological preparations are more effective than
      conventional medications which are often limited by severe side-effects and
      generally less tolerated than biological treatments.

PMID- 22580859
TI  - Estimation of botulinum toxin type A efficacy on spasticity and functional
      outcome in children with spastic cerebral palsy.
AB  - AIM: We evaluated the effects of botulinum toxin type A (BTA) -
      abobotulinumtoxinA on passive motion resistance (PMR) values of lower limbs
      affected muscles and on the functional motor status in children with spastic
      cerebral palsy (CP). METHODS: In Group I (28 lower limbs with spastic muscles),
      and in Group II (14 lower limbs with dynamic spastic equinus) BTA was
      administered. Physical therapy was prescribed for 16 weeks. We estimated PMR
      using the Modified Ashworth Scale. Achieved functional motor level was evaluated
      by Gross Motor Function Classification System (GMFCS) and Gross Motor Function
      Measure (GMFM). Parameters were assessed before treatment and after 3,8,16 weeks
      and 6 months respectively. RESULTS: In Group I, PMR was significantly lower for
      hip adductors and knee extensors over 3-16 weeks, and for ankle joint extensors
      in both groups. There were significant differences for both groups in frequencies
      of GMFCS values after 16 weeks from BTA application. There was a significant
      increase in GMFM scores after 8 and 16 weeks from BTA application in both groups
      of patients. CONCLUSIONS: BTA treatment in CP children is followed by reduction
      in PMR values and improvement in functional motor status.

PMID- 22580860
TI  - Comparative study of intravenous opioid consumption in the postoperative period.
AB  - BACKGROUND: Intravenous patient-controlled analgesia (IV PCA) using opiods is an
      accepted method for delivering postoperative analgesia. The aim of this study was
      to compare fentanyl and tramadol with IV PCA after spinal anesthesia (SA) and
      general anesthesia (GA) following cesarean section (C/S). METHODS: Ninety women
      were randomly assigned to three groups (n=30). Group 1 was treated with IV
      fentanyl PCA after SA. Groups 2 and 3 were treated with IV fentanyl PCA and IV
      tramadol PCA after GA. Outcome measures were recorded for the first 24 h post
      anesthesia. RESULTS: PCA use was significantly lower after SA (P<0.05). Eighteen
      patients in the SA Group and 27 patients and 24 patients from the GA groups
      required additional opioid. Opioid consumption and patient satisfaction were
      similar for groups after GA (P>0.05). 638.4 +/- 179.1 MUg fentanyl was consumed
      by patients of Group 2, 356.3 +/- 87.0 MUg fentanyl and 559.5 +/- 207.0 mg
      tramadol was consumed by Group 1 and Group 3 respectively. There was no
      significant difference in the overall severity and incidence of nausea,
      drowsiness or pruritus. CONCLUSION: Our study shows that analgesic consumption
      and post-operative pain scores after SA in C/S decreased, without increase in
      adverse reactions.

PMID- 22580861
TI  - Comparison of imaging methods in POEMS syndrome.
AB  - BACKGROUND: POEMS syndrome is a clinical condition with a very heterogeneous
      clinical manifestation. Its presentation as well as monitoring is complex and
      dependent on the clinician's experience. One of the leading presenting symptoms
      is based on evaluation of skeletal damage with typical osteosclerotic or mixed
      lesions. AIMS AND METHODS: Our aim was to compare the usefulness of different
      imaging methods in the diagnostics of POEMS syndrome, such as conventional
      radiography, densitometry, technetium scintigraphy, PET/CT scan, MRI and
      angiography on a series of three patients with POEMS syndrome with different
      clinical manifestations and course of disease. RESULTS: Our series demonstrates
      different types of skeletal involvement in POEMS syndrome. Although conventional
      X-ray is the imaging method mostly used for the evaluation, its sensitivity and
      specificity is low. Under specific conditions, other imaging methods should be
      considered, giving a more complex outlook of the disease's skeletal involvement.
      Nevertheless, FDG-PET/CT confirmed its superiority in defining both skeletal
      lesions as well as the activity of the neoplastic process. CONCLUSIONS: We
      conclude that the different manifestation of the disease implies the necessity of
      a complex evaluation of imaging methods in mutual concordance. FDG-PET/CT emerges
      as the most contributive method for the evaluation of both the extent and
      activity of the disease.

PMID- 22580862
TI  - Treatment of obstructive sleep apnea with continuous positive airway pressure
      decreases adipocyte fatty acid-binding protein levels.
AB  - AIM: Obstructive sleep apnea (OSA) can be associated with the metabolic syndrome.
      Adipocyte fatty acid-binding protein (A-FABP) may play a role in OSA. The aim of
      this study was to determine whether continuous positive airway pressure (CPAP)
      treatment results in decreased serum A-FABP levels. SUBJECTS AND METHODS: 81
      patients (70 males, a mean age of 53.9+/-10.3 years) were evaluated by
      polysomnography, diagnosed with OSA and indicated for CPAP treatment.
      Anthropometric, clinical and laboratory investigations were carried out and
      repeated after 1 month/ 1 year of CPAP treatment. The data were analyzed using
      the SPSS Statistics 15 software (SPSS Inc., Chicago, USA). RESULTS: Patients had
      significantly decreased A-FABP levels (34.4 ng/ml, 31.2 ng/ml, 24.8 ng/ml,
      P=0.048, P=0.001) and improved OSA parameters: AHI (53.9, 5.0, 5.6, P<0.0001),
      mean nocturnal oxygen saturation (91%, 93%, 94%, P<0.0001), ODI (55, 9, 8,
      P<0.0001), and percentage of sleep time with oxygen saturation below 90% (28.2,
      0.2, 0, P<0.0001). BMI, waist, neck circumference, and blood pressure did not
      statistically significantly change. CONCLUSION: CPAP therapy in OSA patients has
      a positive effect on A-FABP levels. Decreased A-FABP levels play an important
      role in regulating glucose metabolism and affect the regulation of lipid
      metabolism and thus may contribute to decrease in the cardiovascular
      complications of OSA.

PMID- 22580863
TI  - Clinical anatomy aspects of functional 3D training -- case study.
AB  - INTRODUCTION: Functional 3D training originating in rehabilitation and
      physiotherapy routines, is modelled on the basis of a patient's functional
      impairment and muscle function test results. 3-D functional rehabilitation
      comprises two key components. The first is three-dimensional movements of the
      body and the second is restoration of function, The aim of 3D training is not
      only to improve physical fitness and muscular coordination, it is recommended for
      all age groups regardless of health status. The aim of this review is to
      highlight the main principles, roles and methods of 3D functional training from a
      clinically-anatomical perspective and its application in clinical practice.
      Second, we present a case study of 3d training in an obese boy. METHODS: Database
      search using the lemmatization method and data bases: Web of Knowledge, Web of
      Science, UpToDate, PubMed and Google Scholar for the years 2005-2011. RESULTS AND
      CONCLUSIONS: Functional 3D training is an effective method for, among others,
      strengthening the postural muscles of the human body, increasing articular
      stability, strengthening the ligaments and stability of muscle groups,especially
      the back muscles and for improving lung capacity. The method of functional
      training is of considerable significance in activating the pelvic floor muscles
      and the pelvic-trochanteric muscles for gynegymnastics and incontinence
      prevention. It has application in the prevention of falls in patients with
      neurodegenerative diseases and, as shown below, in the therapy of obesity.

PMID- 22580864
TI  - Principles of supervision in cognitive behavioural therapy.
AB  - BACKGROUND: Psychotherapy requires clinical supervision. This is systematic
      guidance of a therapist by a supervisor. Inevitably, there is a question of
      training new high-quality therapists. This is related to supervision of their
      basic training. Later, it is important to provide an opportunity for lifelong
      supervision throughout the entire psychotherapeutic practice. METHOD: PUBMED data
      base was searched for articles using the key words "supervision in CBT",
      "therapeutic relations", "transference", "countertransference", "schema therapy",
      "dialectical behavioral therapy". The search was repeated by changing the key
      word. No language or time constraints were applied. The lists of references of
      articles detected by this computer data base search were examined manually to
      find additional articles. We also used the original texts of A. T. Beck, J. Beck,
      M. Linehan, R. Leahy, J. Young and others. Basically this is a review with
      conclusions about supervision in cognitive behavioral therapy. RESULTS: The task
      of supervision is obvious - to increase the value of the therapeutic process in
      the client's best interest. At the same time, supervision is an educational
      process in the truest sense of the word, including an opportunity to select one's
      own supervisor. This is a very important procedural aspect since the therapist
      identifies with his/her supervisor, either consciously or unconsciously.
      Establishing the supervisor-supervisee relationship is based on principles
      similar to those in the therapeutic relationship. There is an important parallel
      reflecting the therapist-client relationship. This is because any changes in the
      supervisory process are analogically transferred onto the therapist-client
      relationship. Additionally, supervision is oriented towards increasing the
      therapist's competencies. The CBT therapist's basic skills involve good
      theoretical knowledge, professional behaviour towards clients, ability to use
      specific therapeutic strategies for maintaining the therapeutic relationship,
      sensitivity to parallel processes and accomplishment of changes, and adherence to
      ethical norms. Given the fact that during supervision, the supervisee may be in
      any stage of his/ her training, supervision must take into consideration where
      the therapist is in his/her training and development and what he/she has or has
      not learnt. CONCLUSIONS: Both the literature and our experience underscore the
      importance of careful supervision of cognitive behavioral therapy. The
      supervisory relationship is similar to a therapeutic relationship and the
      supervisee also needs security, acceptance and appreciation for his/her
      professional growth. However, there is more freedom in the relationship.
      Supervision may only lead to the supervisee's professional growth if it supports
      his/her individuality and helps him/her to discover things. Therefore, numerous
      approaches are used in supervision which are associated with the abilities to
      self-reflect and to realize transference and countertransference mechanisms.

PMID- 22580865
TI  - Evaluation of magnetic resonance imaging and clinical outcome after tissue
      engineered cartilage implantation: prospective 6-year follow-up study.
AB  - BACKGROUND: Autologous chondrocyte implantation (ACI) is an important procedure
      when repairing cartilage defects of the knee. We previously reported several
      basic studies on tissue-engineered cartilage, and conducted a multicenter
      clinical study in 2009. In this clinical study, we evaluated the patients'
      clinical scores and MRI findings before and after tissue-engineered cartilage
      implantation, and compared the data obtained at 1 year and approximately 6 years
      post-implantation. METHODS: Fourteen patients who underwent implantation of
      tissue-engineered cartilage to repair cartilage defects of the knee were
      evaluated. Tissue-engineered cartilage was produced by culturing autologous
      chondrocytes three dimensionally in atelocollagen gel. The patients were
      evaluated clinically using the Lysholm score, and the original knee-function
      score at pre-implantation and at 1 year and approximately 6 years post
      implantation. MRI scans were obtained at the same observation periods. A modified
      magnetic resonance observation of cartilage repair tissue (MOCART) system was
      used to quantify clinical efficacy based on the MRI findings. RESULTS: In
      approximately 6 years of follow-up, none of the 14 patients reported any
      subjective symptoms of concern. The mean Lysholm score and the original knee
      function score (63.0 +/- 10.1, 59.9 +/- 5.7) significantly improved at 1 year
      after implantation (86.4 +/- 11.8, 94.1 +/- 9.2), and were maintained until 6
      years after implantation (89.8 +/- 6.2, 89.9 +/- 11.2), although some patients
      showed deterioration of Lysholm and original knee scores between 1 year post
      implantation and the final follow-up. The mean MOCART score was 13.2 +/- 12.0 pre
      implantation, and 62.5 +/- 24.7 at 1 year and 70.7 +/- 22.7 at approximately 6
      years post-implantation. The MOCART scores at 1 year and 6 years were
      significantly higher than the pre-implantation score, but there was no
      significant difference between the scores at 1 and 6 years, indicating that the
      MRI results at 1 year after implantation were maintained for the next 5 years.
      CONCLUSIONS: The clinical scores and MRI findings after implantation of tissue
      engineered cartilage were improved at 1 year after implantation and were
      maintained until 6 years after implantation.

PMID- 22580866
TI  - Clinico-radiological factors affecting the joint space narrowing after
      transtrochanteric anterior rotational osteotomy for osteonecrosis of the femoral
      head.
AB  - PURPOSE: The purpose of this study was to investigate the factors that affect the
      joint space narrowing after transtrochanteric anterior rotational osteotomy (ARO)
      for osteonecrosis of the femoral head (ONFH). METHODS: We reviewed 39 cases (43
      hips) of ONFH in patients who underwent ARO between 2000 and 2004. Their mean age
      was 42 years (23-61) at the time of surgery. The mean follow-up period was 7.3
      years (3-10). The following clinical and radiological factors were investigated:
      the preoperative stage, localization and extent of the necrotic lesion, and the
      postoperative intact ratio (transposed intact articular surface of the femoral
      head to the weight-bearing surface of the acetabulum). The 43 hips were divided
      into two groups: a joint space narrowing (JSN) group and a non-joint space
      narrowing (non-JSN) group. RESULTS: Thirty-seven hips (86 %) were categorized as
      non-JSN and six (14 %) as having JSN. The preoperative Japanese Orthopaedic
      Association score was significantly higher in the non-JSN group than in the JSN
      group (P = 0.01). In the non-JSN group, the rate of early stage disease was
      significantly higher than in the JSN group (P = 0.03). The postoperative intact
      ratio was significantly higher in the non-JSN group than in the JSN group (P =
      0.002). A multivariate analysis revealed that the postoperative intact ratio was
      an independent predictor of the progression of joint space narrowing after ARO,
      and the cutoff point was 39.2 %. CONCLUSION: The results of this study suggest
      that the postoperative intact ratio is one of factors determining the progression
      of joint space narrowing after ARO and that an approximately 40 % or higher
      postoperative intact ratio is recommended to prevent joint space narrowing.

PMID- 22580867
TI  - Total hip arthroplasty combined with double-chevron subtrochanteric osteotomy.
AB  - BACKGROUND: Subtrochanteric femoral shortening and corrective osteotomy are
      regarded as an integral part of total hip arthroplasty for a completely
      dislocated hip or severe deformity of the proximal femur. Alternative femoral
      osteotomy techniques-transverse, oblique, step-cut, and V-shaped, have been
      described. METHODS: In this series, we performed 22 cementless total hip
      arthroplasties combined with double-chevron subtrochanteric osteotomies between
      1997 and 2002. There were 17 females and 2 males. Their average age at the time
      of the operation was 59 years (range 41-74 years). Thirteen hips were completely
      dislocated, 8 hips needed treatment after a proximal femoral osteotomy, and there
      was 1 case of hip ankylosis. RESULTS: The mean length of the operation was 128
      min (range 80-215 min). Mean total blood loss was 1442 g (range 809-2007 g),
      which included both the intraoperative blood loss and postoperative blood loss.
      After an average of 7.6 years of follow-up, the Japanese Orthopaedic Association
      Hip Score improved from 48 to 79. Three types of complication were observed.
      There were 4 early dislocations, 3 proximal splits, and 1 nonunion at the
      osteotomy site. CONCLUSIONS: Our study shows that acceptable results are obtained
      from double-chevron subtrochanteric osteotomy for subtrochanteric femoral
      shortening and corrective osteotomy. However, total hip arthroplasty combined
      with subtrochanteric osteotomy is a technically demanding treatment option.

PMID- 22580868
TI  - Physicochemical property space of hepatobiliary transport and computational
      models for predicting rat biliary excretion.
AB  - Biliary excretion (BE) is a major elimination pathway, and its prediction is
      particularly important for optimization of systemic and/or target-site exposure
      of new molecular entities. The objective is to characterize the physicochemical
      space associated with hepatobiliary transport and rat BE and to develop in silico
      models. BE of 123 in-house compounds was obtained using the bile-duct cannulated
      rat model. Human and rat hepatic uptake transporters (hOATP1B1, hOATP1B3,
      hOATP2B1, and rOatp1b2) substrates (n = 183) were identified using transfected
      cells. Furthermore, the datasets were extended by adding BE of 163 compounds and
      97 organic anion transporting polypeptide (OATP) substrates from the literature.
      Approximately 60% of compounds showing percentage of BE (%BE) >= 10 are anions,
      with mean BE of anions (36%) more than 3-fold higher than that of nonacids (11%).
      Compounds with %BE >= 10 are found to have high molecular mass, large polar
      surface area, more rotatable bonds, and high H-bond count, whereas the
      lipophilicity and passive membrane permeability are lower compared with compounds
      with %BE < 10. According to statistical analysis and principal component
      analysis, hOATPs and rOatp1b2 substrates showed physicochemical characteristics
      that were similar to those of the %BE >= 10 dataset. We further build categorical
      in silico models to predict rat BE, and the models (gradient boosting machine and
      scoring function) developed showed 80% predictability in identifying the rat BE
      bins (%BE >= 10 or < 10). In conclusion, the significant overlap of the property
      space of OATP substrates and rat BE suggests a predominant role of sinusoidal
      uptake transporters in biliary elimination. Categorical in silico models to
      predict rat BE were developed, and successful predictions were achieved.

PMID- 22580869
TI  - Description of a novel approach for intraperitoneal drug delivery and the related
      device.
AB  - BACKGROUND: Two significant limitations of intraperitoneal drug therapy are
      limited drug distribution and poor penetration into peritoneal nodules. A
      possible solution is the application of the so-called "therapeutic
      pneumoperitoneum," taking advantage of the gaseous nature and the pressure of
      capnoperitoneum during laparoscopy. Our objective was to develop a device able to
      apply such therapeutic pneumoperitoneum. METHODS: The technology presented here
      is a spraying device and can be introduced through a trocar. It is driven by
      mechanical pressure and consists of an injector, a line, and a nozzle. An in vivo
      experimental study was performed in five pigs. A transvaginal cholecystectomy was
      performed. At the end of the procedure, a standard dose of methylene blue was
      sprayed/infused into the abdominal cavity for 30 min (4 test animals
      w/therapeutic pneumoperitoneum (12 mmHg CO(2)) and 1 control animal
      w/conventional lavage (2 l intra-abdominal volume with extracorporeal
      circulation)). At the end of the procedure, all animals were autopsied and the
      peritoneum was analyzed. Outcome criteria were: (1) drug distribution (as
      assessed by the stained peritoneal surface at autopsy), and (2) diffusion into
      the peritoneum (presence or not of macroscopic staining of the outer aspect of
      the peritoneum immediately after surgery). RESULTS: Stained peritoneal surface
      was larger after aerosol application compared with peritoneal lavage, and
      staining more intense. Hidden peritoneal surfaces and the anterior abdominal wall
      were stained only in the aerosol group. In contrast to peritoneal lavage, the
      outer aspect of peritoneal membrane was immediately stained after pressurized
      spraying. CONCLUSIONS: This device and the related approach significantly improve
      both distribution and penetration of a test substance into the peritoneal cavity
      in a large animal model. This might be a significant progress in treating
      intraperitoneal disease, in particular peritoneal carcinomatosis.

PMID- 22580870
TI  - Comparative treatment and literature review for laparoscopic splenectomy alone
      versus preoperative splenic artery embolization splenectomy.
AB  - BACKGROUND: Although laparoscopic splenectomy has been gradually regarded as an
      acceptable therapeutic approach for patients with massive splenomegaly,
      intraoperative blood loss remains an important complication. In an effort to
      evaluate the most effective and safe treatment of splenomegaly, we compared three
      methods of surgery for treating splenomegaly, including open splenectomy,
      laparoscopic splenectomy, and a combination of preoperative splenic artery
      embolization plus laparoscopic splenectomy. METHODS: From January 2006 to August
      2011, 79 patients underwent splenectomy in our hospital. Of them, 20 patients
      underwent a combined treatment of preoperative splenic artery embolization and
      laparoscopic splenectomy (group 1), 30 patients had laparoscopic splenectomy
      alone (group 2), and 29 patients underwent open splenectomy (group 3). Patients'
      demographics, perioperative data, clinical outcome, and hematological changes
      were analyzed. RESULTS: Preoperative splenic artery embolization plus
      laparoscopic splenectomy was successfully performed in all patients in group 1.
      One patient in group 2 required an intraoperative conversion to traditional open
      splenectomy because of severe blood loss. Compared with group 2, significantly
      shorter operating time, less intraoperative blood loss, and shorter postoperative
      hospital stay were noted in group 1. No marked significant differences in
      postoperative complications of either group were observed. Compared with group 3,
      group 1 had less intraoperative blood loss, shorter postoperative stay, and fewer
      complications. No significant differences were found in operating time. There was
      a marked increase in platelet count and white blood count in both groups during
      the follow-up period. CONCLUSIONS: Preoperative splenic artery embolization with
      laparoscopic splenectomy reduced the operating time and decreased intraoperative
      blood loss when compared with laparoscopic splenectomy alone or open splenectomy.
      Splenic artery embolization is a useful intraoperative adjunctive procedure for
      patients with splenomegaly because of the benefit of perioperative outcomes.

PMID- 22580871
TI  - Laparoscopic splenectomy: experience of a single center in a series of 300 cases.
AB  - BACKGROUND: Laparoscopic splenectomy (LS) has gradually become the technique of
      choice for surgical removal of the spleen. The aim of this study was to evaluate
      the efficacy of LS in a large cohort of patients from a single center. METHODS:
      From March 1992 to June 2010, 300 patients underwent LS at our hospital for
      predominantly hematologic disorders. The first 92 cases were performed using an
      anterior approach, whereas in the remaining 208 cases a lateral approach with a
      four-trocar technique was used. Patient demographics, diagnosis, and outcomes
      were reviewed. RESULTS: Spleen volume was similar between the anterior (350 ml)
      and the lateral (370 ml) approaches. The lateral approach was associated with
      shorter operative time (60 vs. 80 min), less blood loss (30 vs. 110 ml), and no
      conversion (0 vs. 2.2 %) compared to the anterior approach. Reoperations were
      required in three patients (1.0 %) because of bleeding, subphrenic abscess, and
      intestinal ischemia. Postoperative complications were significantly fewer for the
      lateral (4.8 %) than for the anterior (31.5 %) approach and the hospital stay was
      shorter (3.1 vs. 5.2 days) and there was less postoperative pain. Splenectomy for
      hematologic malignancies resulted in a higher morbidity rate, more postoperative
      pain, and longer hospital stay. Overall mortality rate was 0.3 %. No late
      complications were observed during the 1-5-year follow-up. CONCLUSIONS: LS using
      the lateral approach with the placement of four trocars can be considered the
      procedure of choice for both benign and malignant diseases affecting the spleen.
      Extensive experience and technical standardization help to avoid surgical
      pitfalls, providing an adequate control of hemostasis, the excision of accessory
      spleens (AS), and the avoidance of parenchymal rupture.

PMID- 22580872
TI  - A comparative study of surgery and endoscopy for the treatment of bile duct
      stricture in patients with chronic pancreatitis.
AB  - BACKGROUND: This study aimed to compare the outcomes of endoscopic treatment (ET)
      and surgical treatment (ST) for common bile duct (CBD) stricture in patients with
      chronic pancreatitis (CP). METHODS: From 2004 to 2009, 39 patients (35 men and 4
      women; median age, 52 years; range, 38-66 years) were referred for CBD stricture
      in CP. Of these 39 patients, 33 (85 %) underwent primary ET, and 6 underwent
      primary ST. Treatment success was defined in both groups as the absence of signs
      denoting recurrence, with normal serum bilirubin and alkaline phosphatase levels
      after permanent stent removal in ET group. The follow-up period was longer than
      12 months for all the patients. RESULTS: For the patients treated with ET, the
      mean number of biliary procedures was 3 (range, 1-10) per patient including
      extractible metallic stents in 35 % and multiple plastic stents in 65 % of the
      patients. The mean duration of stent intubation was 11 months. The surgical
      procedure associated with biliary drainage (4 choledochoduodenostomies, 1
      choledochojejunostomy, and 1 biliary decompression within the pancreatic head)
      was a Frey procedure for five patients and a pancreaticojejunostomy for one
      patient. The overall morbidity rate was higher in the ST group. The total
      hospital length of stay was similar in the two groups (16 vs 24 days,
      respectively; p = 0.21). In terms of intention to treat, the success rates for ST
      and ET did not differ significantly (83 % vs 76 %; p = 0.08). Due to failure, 17
      patients required ST after ET. Event-free survival was significantly longer in
      the ST group (16.9 vs 5.8 months; p = 0.01). The actuarial success rates were 74
      % at 6 months, 74 % at 12 months, and 65 % at 24 months in the ST group and
      respectively 75 %, 69 %, and 12 % in the ET group (p = 0.01). After more than
      three endoscopic procedures, the success rates were 27 % at 6 months and 18 % at
      18 months. CONCLUSION: For bile duct stricture in CP, surgery is associated with
      better long-term outcomes than endoscopic therapy. After more than three
      endoscopic procedures, the success rate is low.

PMID- 22580873
TI  - Radiofrequency versus ultrasonic energy in laparoscopic colorectal surgery: a
      metaanalysis of operative time and blood loss.
AB  - BACKGROUND: Various energy sources are available for tissue dissection and vessel
      sealing in laparoscopic colorectal surgery. The electrothermal bipolar vessel
      sealing system (EBVS) and ultrasonic energy (UE) devices are widely used to
      provide hemostatic dissection in laparoscopic procedures. Nevertheless, available
      evidenced-based data comparing their operative results still are scarce. This
      study conducted a metaanalysis of controlled clinical trials comparing EBVS and
      UE in terms of operative time and intraoperative blood losses in laparoscopic
      colorectal surgery. METHODS: The MEDLINE and Embase databases were searched using
      medical subject headings and free text words. All randomized controlled trials
      (RCTs) and controlled clinical trials using EBVS and UE in laparoscopic
      colorectal surgery were considered for inclusion in the study. Random effects
      models were used in case of heterogeneity to obtain summary statistics for the
      overall difference in operating time and blood loss between instruments. RESULTS:
      Four studies comparing EBVS with UE for 397 patients (200 EBVS vs. 197 UE
      patients) were included in the study. The findings showed that EBVS was
      associated with a significantly shorter operative time and less intraoperative
      blood loss than UE (p < 0.05). CONCLUSIONS: The metaanalysis indicated that EBVS
      is associated with a shorter operative time and less blood loss than UE in
      laparoscopic colorectal surgery. However, these results should be interpreted
      with caution due to the high heterogeneity of the included trials and the limited
      number of studies with a high level of evidence. More adequately designed RCTs
      with a larger number of patients are required to confirm the results of this
      metaanalysis.

PMID- 22580874
TI  - Three-dimensional vision enhances task performance independently of the surgical
      method.
AB  - BACKGROUND: Within the next few years, the medical industry will launch
      increasingly affordable three-dimensional (3D) vision systems for the operating
      room (OR). This study aimed to evaluate the effect of two-dimensional (2D) and 3D
      visualization on surgical skills and task performance. METHODS: In this study, 34
      individuals with varying laparoscopic experience (18 inexperienced individuals)
      performed three tasks to test spatial relationships, grasping and positioning,
      dexterity, precision, and hand-eye and hand-hand coordination. Each task was
      performed in 3D using binocular vision for open performance, the Viking 3Di
      Vision System for laparoscopic performance, and the DaVinci robotic system. The
      same tasks were repeated in 2D using an eye patch for monocular vision,
      conventional laparoscopy, and the DaVinci robotic system. RESULTS: Loss of 3D
      vision significantly increased the perceived difficulty of a task and the time
      required to perform it, independently of the approach (P < 0.0001-0.02). Simple
      tasks took 25 % to 30 % longer to complete and more complex tasks took 75 %
      longer with 2D than with 3D vision. Only the difficult task was performed faster
      with the robot than with laparoscopy (P = 0.005). In every case, 3D robotic
      performance was superior to conventional laparoscopy (2D) (P < 0.001-0.015).
      CONCLUSIONS: The more complex the task, the more 3D vision accelerates task
      completion compared with 2D vision. The gain in task performance is independent
      of the surgical method.

PMID- 22580875
TI  - Endoscopic muscularis dissection for upper gastrointestinal subepithelial tumors
      originating from the muscularis propria.
AB  - BACKGROUND AND AIMS: Based on our experience with endoscopic submucosal
      dissection (ESD) and new endoscopic techniques for endoscopic closure of
      iatrogenic upper gastrointestinal (upper-GI) perforations, we developed methods
      to remove upper-GI subepithelial tumors (SETs) originating from the muscularis
      propria by endoscopic muscularis dissection (EMD). The aim of this study is to
      evaluate the clinical feasibility and safety of EMD. METHODS: 31 patients with
      upper-GI SETs originating from the muscularis propria were treated by EMD. The
      EMD differed from ESD in (1) precutting the overlying mucosa above the lesion by
      using snare or longitudinal incision instead of circumferential incision, (2)
      dissecting the complete tumors away from submucosal and muscularis propria tissue
      by electrical dissection combined with blunt dissection, and (3) closing the
      wound with clips. Perforations occurring during dissection were closed by
      endoscopic methods. RESULTS: 30 of 31 tumors were resected completely (96.8 %).
      One esophageal lesion was resected partially because of severe adhesions with
      surrounding tissue. Mean resected tumor size was 22.1 mm * 15.5 mm, and mean
      operation time was 76.8 min (range 15-330 min). Histological diagnosis was
      gastrointestinal stromal tumor (GIST) in 16 lesions [6 esophageal, 3 cardial, 7
      gastric; 6 very low risk and 10 low risk according to the National Institutes of
      Health (NIH) risk classification] and leiomyoma in 15 lesions (8 esophageal, 4
      cardial, 3 gastric). No patient developed delayed hemorrhage. Perforation
      occurred in four patients (12.9 %), all of which were managed successfully by
      endoscopic techniques. The mean follow-up time was 17.7 months (range 7-35
      months). Follow-up found no tumor recurrence in any patient. CONCLUSIONS: In this
      early experience, EMD appears to be a feasible and minimally invasive treatment
      for some patients with upper-GI SETs originating from the muscularis propria.
      Although there is a higher risk of perforation than with ESD, this will improve
      with extended practice, and perforations have become manageable endoscopically.

PMID- 22580876
TI  - Is it worthwhile to preserve adult spleen in laparoscopic distal pancreatectomy?
      Perioperative and patient-reported outcome analysis.
AB  - BACKGROUND: Despite the emphasis on its role, the spleen has commonly been
      removed in distal pancreatectomy. We designed this study to evaluate the efficacy
      of spleen salvage during laparoscopic distal pancreatectomy for patients with
      benign and borderline malignant tumors. MATERIALS AND METHODS: From February 2005
      to December 2010, 40 patients underwent spleen-preserving laparoscopic distal
      pancreatectomy (Sp-Lap DP) and 32 patients underwent laparoscopic distal
      pancreatosplenectomy (Lap DPS). Medical records were retrospectively reviewed,
      and a specially designed questionnaire was administered to the patients for the
      follow-up study. RESULTS: The demographics and final diagnoses were similar
      between the two groups. The operative time was significantly longer in the Sp-Lap
      DP group (303.9 +/- 136.0 versus 239.0 +/- 94.9 min, p = 0.024). Patients in the
      Lap DPS group had more postoperative pancreatic fistulas of higher grade (p =
      0.026). A higher grade of postoperative complications occurred more frequently in
      the Lap DPS group (p = 0.003). Consequently, postoperative hospital stay was
      significantly shorter for Sp-Lap DP than for Lap DPS patients (7.1 +/- 2.3 versus
      12.5 +/- 10.8 days, p = 0.004). On the follow-up survey, episodes of common cold
      or flu were apparently more frequent in the Lap DPS group (p = 0.026). Despite
      the similar recovery period between the two groups, significantly more patients
      who underwent Lap DPS felt fatigue (p = 0.014) and poorer health condition (p =
      0.042). CONCLUSIONS: In addition to frequent higher-grade complications and
      prolonged hospital stays, Lap DPS appeared to impair patient quality of life
      based on follow-up survey. Even an effort to preserve adult spleen in distal
      pancreatectomy is worthwhile.

PMID- 22580877
TI  - Deep sedation in natural orifice transluminal endoscopic surgery (NOTES): a
      comparative study with dogs.
AB  - BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) has been
      mostly performed with the animal under general and inhalational anesthesia (IA
      NOTES). To date, NOTES using propofol sedation (PS-NOTES) has not been
      investigated. This study aimed to assess the feasibility and safety of PS-NOTES
      for transgastric oophorectomy with carbon dioxide insufflation and to compare its
      success rates with those of conventional IA-NOTES. METHODS: In this prospective
      randomized study, NOTES oophorectomy was performed for 19 female dogs randomized
      to two conditions: PS (study group) and IA (control group). Sedation success
      rates (ability to visualize and resect ovaries without converting to IA),
      operative success rates (ability to resect and retrieve both ovaries in full
      using only NOTES), and vital parameters including hemodynamic and respiratory
      changes were documented. RESULTS: In the PS-NOTES group (n = 9), the sedation
      success rate was 100 %. The operative success rate was 67 % (6 of 9 animals)
      compared with 80 % (8 of 10 animals) in the IA-NOTES group. No purposeful
      movement occurred during surgical manipulation and no respiratory or
      cardiovascular complications in occurred the PS group. Heart rate (HR) and end
      tidal carbon dioxide (ETCO(2)) were significantly higher in the PS group than in
      the IA group. Blood pressure (BP) was significantly higher in the PS group only
      during the middle part of the procedure. Only mild respiratory depression was
      noted in the PS group, as indicated by elevated but acceptable ETCO(2).
      Elevations in BP and HR are thought to be related to elevated CO(2) but did not
      appear to have an adverse impact on the course of the procedure. Recovery was
      uneventful for all the animals. CONCLUSION: The use of PS-NOTES appears to be
      feasible, resulting in outcomes comparable with those for IA in dogs. Further
      studies are needed to determine the applicability of this concept in human NOTES.

PMID- 22580878
TI  - High incidence of symptomatic incisional hernia after midline extraction in
      laparoscopic colon resection.
AB  - BACKGROUND: The incidence of incisional hernia has not decreased despite the use
      of laparoscopy for colon resections. The objective of this study is to evaluate
      the impact of the incision used for specimen extraction on the incidence of
      incisional hernia after laparoscopic colectomy. METHODS: Patients who underwent
      laparoscopic colectomy without stoma at a single university tertiary-care centre
      from 2003 to 2009 were identified from an operating room database. Patients were
      contacted by telephone for participation, and underwent physical examination +/-
      ultrasonography for incisional hernia at the specimen extraction site and
      completed the Body Image Questionnaire. Specimen extraction incisions were
      classified into midline, transverse and Pfannenstiel groups. RESULTS: Out of a
      total of 251 patients, 99 patients agreed to participate (68 midline, 7
      transverse, 24 Pfannenstiel), while 73 patients refused consent and 79 patients
      could not be contacted. Patients who refused consent were older (69.8 vs 62.4
      years, p = 0.001) but otherwise were similar to participants with respect to
      gender, malignant disease, postoperative complications and extraction site. Mean
      length of follow-up was 37.0 months. The overall incidence of incisional hernia
      was 21% (21/99), being 29 % (20/68) after midline incision compared with 14 %
      (1/7) after transverse and 0 % (0/24) after Pfannenstiel incisions (p = 0.002).
      Of patients with incisional hernia, 47 % (10/21) were symptomatic. Patients with
      incisional hernia had lower cosmetic score (14.4 vs 17.7, p = 0.02) compared with
      those without, but there was no difference in body image score. There were no
      differences in body image or cosmesis between the three incisions. CONCLUSIONS:
      There is a high incidence of symptomatic incisional hernia after midline specimen
      extraction in laparoscopic colectomy, which negatively impacts cosmesis. The risk
      of hernia may be lower with the use of a transverse or Pfannenstiel incision for
      specimen extraction.

PMID- 22580879
TI  - Radiofrequency energy antenna coupling to common laparoscopic instruments:
      practical implications.
AB  - BACKGROUND: Electromagnetic coupling can occur between the monopolar "Bovie"
      instrument and other laparoscopic instruments without direct contact by a
      phenomenon termed antenna coupling. The purpose of this study was to determine
      if, and to what extent, radiofrequency energy couples to other common
      laparoscopic instruments and to describe practical steps that can minimize the
      magnitude of antenna coupling. METHODS: In a laparoscopic simulator, monopolar
      radiofrequency energy was delivered to an L-hook. The tips of standard,
      nonelectrical laparoscopic instruments (either an unlit 10 mm telescope or a 5 mm
      grasper) were placed adjacent to bovine liver tissue and were never in contact
      with the active electrode. Thermal imaging quantified the change in tissue
      temperature nearest the tip of the telescope or grasper at the end of a 5 s
      activation of the active electrode. RESULTS: A 5 s activation (30 watts,
      coagulation mode, 4 cm separation between instruments) increased tissue
      temperature compared with baseline adjacent to the grasper tip (2.2 +/- 2.2 
      degrees C; p = 0.013) and telescope tip (38.2 +/- 8.0  degrees C; p < 0.001). The
      laparoscopic telescope tip increased tissue temperature more than the
      laparoscopic grasper tip (p < 0.001). Lowering the generator power from 30 to 15
      Watts decreased the heat generated at the telescope tip (38.2 +/- 8.0 vs. 13.5 +/
      7.5  degrees C; p < 0.001). Complete separation of the camera/light cords and
      the active electrode cord decreased the heat generated near the telescope tip
      compared with parallel bundling of the cords (38.2 +/- 8.0 vs. 15.7 +/- 11.6 
      degrees C; p < 0.001). CONCLUSIONS: Commonly used laparoscopic instruments couple
      monopolar radiofrequency energy without direct contact with the active electrode,
      a phenomenon that results in heat transfer from a nonelectrically active
      instrument tip to adjacent tissue. Practical steps to minimize heat transfer
      resulting from antenna coupling include reducing the monopolar generator power
      setting and avoiding of parallel bundling of the telescope and active electrode
      cords.

PMID- 22580880
TI  - Laparoscopic splenectomy for massive splenomegaly in benign hematological
      diseases.
AB  - BACKGROUND: Laparoscopic splenectomy has become the standard of care for benign
      hematological disease affecting the spleen; its role in massive splenomegaly
      remains controversial. In this study, we evaluated the outcome of laparoscopic
      splenectomies in terms of spleen size in a group of 83 patients of benign
      hematological diseases. METHODS: From July 2003 to December 2009, 83 patients
      underwent laparoscopic splenectomy for various benign hematological diseases. The
      data were recorded and analyzed in a retrospective manner. The patients were
      divided in to two groups according to the spleen weight; group I < 2,000 g (n =
      54) and group II > 2,000 g (n = 29). Age, sex, hematological condition, operative
      time, estimated blood loss, conversion to open surgery, splenic weight, length of
      hospital stay, time to liquid diet, and morbidity were all recorded. RESULTS:
      Laparoscopic splenectomy was completed in 79 patients (95.2 %). Operative time (p
      = 0.01) and estimated blood loss (p = 0.001) was more in group II. The length of
      hospital stay (p = 0.05) and the postoperative morbidity (p = 0.001) also were
      significantly more in the second group. There was no mortality. CONCLUSIONS:
      Laparoscopic splenectomy is possible and safe for massive splenomegaly in
      hematological disease (>2,000 g), but it needs longer operative time and hospital
      stay.

PMID- 22580881
TI  - Intrahepatic choledochoscopy during trans-cystic common bile duct exploration;
      technique, feasibility and value.
AB  - BACKGROUND: Transcystic laparoscopic common bile duct exploration (TC-LCBDE) is
      advantageous for exploring the bile duct. Choledochoscopy, however, may be quite
      challenging to perform transcystically because the cystic duct is usually narrow,
      duct anatomy may be unfavorable, and not all stones are amenable to transcystic
      extraction. Convention suggests that it is technically very difficult to
      visualize the intrahepatic bile ducts with transcystic choledochoscopy, due to
      the angle of insertion of the cystic into the common bile duct (CBD). However, we
      have performed intrahepatic choledochoscopy successfully, moving the
      choledochoscope from the CBD into the common hepatic duct by using what we have
      termed a "wiper blade maneuver". The purpose of this study was to confirm how
      often this was possible. METHODS: A search of a prospectively collected database
      of patients undergoing routine intraoperative cholangiography (IOC) and
      laparoscopic CBD exploration under the care of a single consultant surgeon was
      performed. RESULTS: A total of 592 LCBDEs were performed between September 1992
      and January 2011; 325 were transcystic explorations. Of these, 72.5 % were female
      and 56 % were admitted acutely. Exploration and duct clearance was performed by
      blind Dormia basket trawling in 63 %. The choledochoscope was utilized in 120
      cases (37 %). The 3-mm choledochoscope was used in 66 (55 %) and the 5-mm scope
      in 54 (45 %). Intrahepatic choledochoscopy was performed in 49 patients (40.8 %).
      Length of surgery was 40-350 min (median 90 min; standard deviation 49 min).
      CONCLUSIONS: It is technically challenging to perform intrahepatic
      choledochoscopy with a 3-mm choledochoscope due to its narrow gauge. The more
      rigid 5-mm scope is thus preferred, but is limited in TCE because its effective
      use depends on the presence of a dilated cystic duct. Despite the technical
      limitations of both caliber scopes, we have demonstrated that intrahepatic
      choledochoscopy during TCE is possible, with each, in 40 % of cases.

PMID- 22580882
TI  - Short-term outcomes of laparoscopic intersphincteric resection from a phase II
      trial to evaluate laparoscopic surgery for stage 0/I rectal cancer: Japan Society
      of Laparoscopic Colorectal Surgery Lap RC.
AB  - BACKGROUND: Laparoscopic intersphincteric resection (Lap ISR) is not yet an
      established technique and its safety and feasibility are unclear. Our aim was to
      clarify the safety and feasibility of Lap ISR for clinical stage 0/I rectal
      cancer (Lap RC) in a prospective multicenter study of laparoscopic surgery in
      Japan. METHODS: To examine the technical and oncological feasibility of
      laparoscopic surgery for rectal cancer, we conducted a confirmatory phase II
      trial to evaluate laparoscopic surgery for preoperative clinical stage 0/I rectal
      cancer. Eligibility criteria included histologically proven carcinoma, size <= 8
      cm, age 20-75 years, no bowel obstruction, and no prior chemotherapy or
      radiotherapy. Between February 2008 and September 2010, 495 patients with rectal
      cancer underwent laparoscopic surgery at 43 institutions. Patients' background
      characteristics and operative and postoperative outcomes were recorded
      prospectively. RESULTS: Seventy-seven patients (15.6 %) underwent Lap ISR. A
      diverting stoma was created in 69 patients (89.6 %). Conversion to open surgery
      occurred in 4 patients (5.2 %): 2 patients were converted because of
      uncontrollable bleeding, and the other 2 patients because of the need for pelvic
      side wall lymphadenectomy. There was no mortality. Median operative time was 345
      min (range = 198-565), median amount of blood loss was 100 ml (range = 0-1760),
      and three patients (3.9 %) were transfused intraoperatively. The median number of
      dissected lymph nodes was 14 (range = 3-33), and all (proximal, distal, and
      vertical) pathological cut margins were negative. Postoperative complications of
      grade 2 or more were detected in 17 patients (22.1 %), including anastomotic
      leakage in 5 (6.4 %), bowel obstruction in 5 (6.5 %), and surgical site infection
      in 2 (2.6 %). Abdominal drainage and diverting stoma were necessary in two
      patients (2.6 %) due to anastomotic leakage. Median length of postoperative
      hospital stay was 13 days (range = 7-167). CONCLUSION: Lap ISR was feasible and
      safe for clinical stage 0/I rectal cancer with favorable short-term outcome.

PMID- 22580884
TI  - Retraction note: Reduction of postoperative nausea, vomiting, and analgesic
      requirement with dexamethasone for patients undergoing laparoscopic
      cholecystectomy.

PMID- 22580883
TI  - Trends in adolescent bariatric surgery evaluated by UHC database collection.
AB  - BACKGROUND: With increasing childhood obesity, adolescent bariatric surgery has
      been increasingly performed. We used a national database to analyze current
      trends in laparoscopic bariatric surgery in the adolescent population and related
      short-term outcomes. METHODS: Discharge data from the University Health System
      Consortium (UHC) database was accessed using International Classification of
      Disease codes during a 36 month period. UHC is an alliance of more than 110
      academic medical centers and nearly 250 affiliate hospitals. All adolescent
      patients between 13 and 18 years of age, with the assorted diagnoses of obesity,
      who underwent laparoscopic adjustable gastric banding (LAGB), sleeve gastrectomy
      (SG), and laparoscopic Roux-en-Y gastric bypass (LRYGB) were evaluated. The main
      outcome measures analyzed were morbidity, mortality, length of hospital stay
      (LOS), overall cost, intensive care unit (ICU) admission rate, and readmission
      rate. These outcomes were compared to those of adult bariatric surgery. RESULTS:
      Adolescent laparoscopic bariatric surgery was performed on 329 patients. At the
      same time, 49,519 adult bariatric surgeries were performed. One hundred thirty
      six adolescent patients underwent LAGB, 47 had SG, and 146 patients underwent
      LRYGB. LAGB has shown a decreasing trend (n = 68, 34, and 34), while SG has shown
      an increasing trend (n = 8, 15, and 24) over the study years. LRYGB remained
      stable (n = 44, 60, and 42) throughout the study period. The individual and
      summative morbidity and mortality rates for these procedures were zero. Compared
      to adult bariatric surgery, 30 day in-hospital morbidity (0 vs. 2.2 %, p < 0.02),
      the LOS (1.99 +/- 1.37 vs. 2.38 +/- 3.19, p < 0.03), and 30 day readmission rate
      (0.30 vs. 2.02 %, p < 0.05) are significantly better for adolescent bariatric
      surgery, while the ICU admission rate (9.78 vs. 6.30 %, p < 0.02) is higher and
      overall cost ($9,375 +/- 6,452 vs. $9,600 +/- 8,016, p = 0.61) is comparable.
      CONCLUSION: Trends in adolescent laparoscopic bariatric surgery reveal the
      increased use of sleeve gastrectomy and adjustable gastric banding falling out of
      favor.

PMID- 22580885
TI  - Efficacy of the over-the-scope clip (OTSC) for treatment of colorectal
      postsurgical leaks and fistulas.
AB  - BACKGROUND: Colorectal postsurgical leaks and fistulas are severe complications
      that dramatically increase morbidity and mortality. The aim of this study was to
      evaluate the clinical impact of over-the-scope clip (OTSC) closure to seal the
      visceral wall in the management of acute and chronic colorectal postsurgical
      leaks and fistulas. METHODS: We reviewed our prospective series of acute and
      chronic colorectal postsurgical leaks and fistulas observed between April 2008
      and September 2011 and treated by OTSC. Indications were all cases with an
      orifice <15 mm in maximum diameter with no extraluminal abscess and luminal
      stenosis. RESULTS: Endoscopic OTSC closure was performed in 14 consecutive
      patients (mean defect = 9.1 mm in diameter) by means of 10.5- or 12-mm clips,
      depending on the wall defect diameter. In eight cases, the indication was an
      acute leak and in six cases a chronic leak, mainly after anterior rectal
      resection; two cases were complicated by a rectovaginal fistula and in two other
      cases by a colocutaneous fistula. OTSC treatment was used to complete endoscopic
      vacuum-assisted closure of a large defect in three cases. The overall success
      rate was 86 % (12/14): 87 % (7/8) in acute and 83 % (5/6) in chronic cases. No
      OTSC-related complications occurred. Further surgery was required in one case.
      CONCLUSION: Endoscopic OTSC closure of colorectal postsurgical leaks and fistulas
      is a safe technique, with a high success rate in both acute and chronic cases,
      including rectovaginal and colocutaneous fistulas.

PMID- 22580886
TI  - Interleukin gene polymorphisms in pneumoconiosis.
AB  - Inhaled asbestos fibres are known to cause inflammation processes with the result
      of lung or pleural fibrosis and malignancies. Interleukins (IL), such as IL
      1beta, IL-6 and IL-10, have various functions in the regulation of the
      inflammatory response and in proliferative processes after inhalation of silica
      dust and can, therefore, influence the pathogenesis of asbestos-induced fibrosis
      and carcinogenesis. Polymorphisms within these genes may be associated with
      susceptibility to silica and asbestos-induced lung diseases. Thus, IL-1beta, IL-6
      and IL-10 polymorphisms were examined to determine an association with asbestos
      or silica-induced fibrosis or malignancies. Association studies were performed in
      1180 individuals, using control subjects (n=177), fibrosis patients (n=605), lung
      cancer (LC) patients (n=364) and malignant mesothelioma (MM) patients (n=34). IL
      1beta (C-511T; C+3954T), IL-6 (G-174C) as well as IL-10 (G-1082A) polymorphisms
      were investigated. Compared to a healthy (control) group, a higher risk was seen
      for malignant mesothelioma patients in all investigated polymorphisms. The IL-6 
      174C allele showed a tendency towards a higher risk for fibrosis or asbestos
      induced lung cancer (ORasbestosis, 1.338; 95% CI, 0.71-2.53; ORsilicosis, 1.226;
      95% CI, 0.54-2.81; ORfibrosis other aetiology, 1.313; 95% CI, 0.58-2.98 and ORLC
      asbestos, 2.112; 95% CI, 0.75-5.92). The IL-10 -1082A carrier seemed to be at
      higher risk for silicosis (ORsilicosis, 2.064; 95% CI, 0.78-5.49) but not for
      asbestosis. In summary, this study did not reveal sufficient evidence for a
      significant association of the investigated interleukin polymorphisms with
      asbestos or silica-induced diseases in the population studied.

PMID- 22580887
TI  - Identification of antifungal compounds produced by Lactobacillus casei AST18.
AB  - Lactobacillus casei AST18 was screened as an antifungal lactic acid bacteria
      which we have reported before. In this research, the antifungal properties of
      cell-free culture filtrate (CCF) from L. casei AST18 were detected, and the
      antifungal compounds of CCF were prepared by ultrafiltration, and semi
      preparative HPLC, and then determined by GC-MS. CCF was sensitive to pH and heat
      treatment but it was not affected by the treatment of trypsin and pepsin. Through
      the treatment of ultrafiltration and semi-preparative HPLC there were two parts
      of CCF which showed antifungal activities: part 1 and part 4. Lactic acid was
      identified as the main antifungal compound in part 1. In part 4, three small
      molecular substances were detected with GC-MS. The three potential antifungal
      substances were cyclo-(Leu-Pro), 2,6-diphenyl-piperidine, and 5,10-diethoxy
      2,3,7,8-tetrahydro-1H,6H-dipyrrolo[1,2-a;1',2'-d]pyrazine. The antifungal
      activity of L. casei AST18 was a synergistic effect of lactic acid and
      cyclopeptides.

PMID- 22580888
TI  - Combined effect of enterocin and lipase from Enterococcus faecium NCIM5363
      against food borne pathogens: mode of action studies.
AB  - Food borne diseases have a major impact on public health whose epidemiology is
      rapidly changing. The whole cells of pathogens involved or their
      toxins/metabolites affect the human health apart from spoiling sensory properties
      of the food products finally affecting the food industry as well as consumer
      health. With pathogens developing mechanisms of antibiotic resistance, there has
      been an increased need to replace antibiotics as well as chemical additives with
      naturally occurring bacteriocins. Bacteriocins are known to act mainly against
      Gram-positive pathogens and with little or no effect towards Gram-negative
      enteric bacteria. In the present study, combination effect of lipase and
      bacteriocin produced by Enterococcus faecium NCIM5363, a highly lipolytic lactic
      acid bacterium against various food pathogens was assessed. The lipase in
      combination with enterocin exhibited a lethal effect against Gram-negative
      pathogens. Scanning electron microscopy studies carried out to ascertain the
      constitutive mode of action of lipase and enterocin revealed that the lipase
      degrades the cell wall of Gram-negative bacteria and creates a pore through which
      enterocin enters thereby resulting in cell death. The novelty of this work is the
      fact that this is the first report revealing the synergistic effect of lipase
      with enterocin against Gram-negative bacteria.

PMID- 22580889
TI  - Pseudomonas kuykendallii sp. nov.: a novel gamma-proteobacteria isolated from a
      hexazinone degrading bioreactor.
AB  - Three strains of Gram-negative bacteria designated strains H2(T), H6, and H7 were
      isolated from bioreactors that degraded the herbicide hexazinone. Similar
      morphological characteristics, cellular fatty acid profiles, and 16S rRNA gene
      sequences show that the isolates are members of the same species. These
      characteristics also show that the isolates belong to the genus Pseudomonas with
      P. graminis, P. putida, and P. stutzeri as close relatives. The 16S rRNA gene of
      the H2(T) strain differed from that of type strains for P. graminis, P. putida,
      and P. stutzeri by 1.9, 2.5, and 2.7 %, respectively, indicating that the H2(T),
      H6, and H7 strains are related to P. graminis, P. putida, and P. stutzeri but are
      different enough to represent a novel species. The G+C content of the three
      strains averaged 61.2 +/- 0.8 mol% which is similar to the values reported for P.
      graminis (61), P. putida (61.6), and P. stutzeri (62.2-65.5). The major cellular
      fatty acids present in the H2(T) strain were C(18:1) omega7c/C (18:1) omega6c
      (34.3 %), C(16:1) omega6c/C(16:1) omega7c (27.4 %), C(16:0) (20.6 %), C(12:0)
      (7.9 %), C(12:0) 3-OH (4.5 %), and C(10:0) 3-OH (3.1 %). The name Pseudomonas
      kuykendallii sp. nov. is proposed for these bacteria.

PMID- 22580890
TI  - A dynamical model of the spindle position checkpoint.
AB  - The orientation of the mitotic spindle with respect to the polarity axis is
      crucial for the accuracy of asymmetric cell division. In budding yeast, a
      surveillance mechanism called the spindle position checkpoint (SPOC) prevents
      exit from mitosis when the mitotic spindle fails to align along the mother-to
      daughter polarity axis. SPOC arrest relies upon inhibition of the GTPase Tem1 by
      the GTPase-activating protein (GAP) complex Bfa1-Bub2. Importantly, reactions
      signaling mitotic exit take place at yeast centrosomes (named spindle pole
      bodies, SPBs) and the GAP complex also promotes SPB localization of Tem1. Yet,
      whether the regulation of Tem1 by Bfa1-Bub2 takes place only at the SPBs remains
      elusive. Here, we present a quantitative analysis of Bfa1-Bub2 and Tem1
      localization at the SPBs. Based on the measured SPB-bound protein levels, we
      introduce a dynamical model of the SPOC that describes the regulation of Bfa1 and
      Tem1. Our model suggests that Bfa1 interacts with Tem1 in the cytoplasm as well
      as at the SPBs to provide efficient Tem1 inhibition.

PMID- 22580891
TI  - 4D non-uniformly sampled HCBCACON and 1J(NCalpha)-selective HCBCANCO experiments
      for the sequential assignment and chemical shift analysis of intrinsically
      disordered proteins.
AB  - A pair of 4D NMR experiments for the backbone assignment of disordered proteins
      is presented. The experiments exploit (13)C direct detection and non-uniform
      sampling of the indirectly detected dimensions, and provide correlations of the
      aliphatic proton (H(alpha), and H(beta)) and carbon (C(alpha), C(beta)) resonance
      frequencies to the protein backbone. Thus, all the chemical shifts regularly used
      to map the transient secondary structure motifs in the intrinsically disordered
      proteins (H(alpha), C(alpha), C(beta), C', and N) can be extracted from each
      spectrum. Compared to the commonly used assignment strategy based on matching the
      C(alpha) and C(beta) chemical shifts, inclusion of the H(alpha) and H(beta)
      provides up to three extra resonance frequencies that decrease the chance of
      ambiguous assignment. The experiments were successfully applied to the original
      assignment of a 12.8 kDa intrinsically disordered protein having a high content
      of proline residues (26 %) in the sequence.

PMID- 22580892
TI  - An improved algorithm for MFR fragment assembly.
AB  - A method for generating protein backbone models from backbone only NMR data is
      presented, which is based on molecular fragment replacement (MFR). In a first
      step, the PDB database is mined for homologous peptide fragments using
      experimental backbone-only data i.e. backbone chemical shifts (CS) and residual
      dipolar couplings (RDC). Second, this fragment library is refined against the
      experimental restraints. Finally, the fragments are assembled into a protein
      backbone fold using a rigid body docking algorithm using the RDCs as restraints.
      For improved performance, backbone nuclear Overhauser effects (NOEs) may be
      included at that stage. Compared to previous implementations of MFR-derived
      structure determination protocols this model-building algorithm offers improved
      stability and reliability. Furthermore, relative to CS-ROSETTA based methods, it
      provides faster performance and straightforward implementation with the option to
      easily include further types of restraints and additional energy terms.

PMID- 22580893
TI  - NMR structure note: the ferrous iron transport protein C (FeoC) from Klebsiella
      pneumoniae.

PMID- 22580894
TI  - Data quality challenges in systemic lupus erythematosus trials: how can this be
      optimized?
AB  - Major scientific advances in basic science, pharmacology, and translational
      medicine have allowed the discovery of new molecular targets whose manipulation
      by new chemical entities has led to treatments for inflammatory diseases,
      including rheumatoid arthritis, multiple sclerosis, and inflammatory bowel
      disease. Development of new agents for systemic lupus erythematosus (SLE) has
      lagged, however, because the protean manifestations of SLE present challenges for
      measuring therapeutic effects in a consistent manner. Composite end points
      combining several Disease Activity Indices (DAIs) are being used in ongoing
      global studies, but the uniform application of these complex DAIs across large
      numbers of clinical sites has proven difficult. We describe herein approaches
      that are being utilized to facilitate collection, review, and analysis of the
      clinical measures utilizing independent central adjudication committees.

PMID- 22580895
TI  - Antithrombotic potential of blockers of store-operated calcium channels in
      platelets.
AB  - OBJECTIVE: Platelet Orai1 channels mediate store-operated Ca(2+) entry (SOCE),
      which is required for procoagulant activity and arterial thrombus formation.
      Pharmacological blockage of these channels may provide a novel way of
      antithrombotic therapy. Therefore, the thromboprotective effect of SOCE blockers
      directed against platelet Orai1 is determined. METHODS AND RESULTS: Candidate
      inhibitors were screened for their effects on SOCE in washed human platelets.
      Tested antagonists included the known compounds, SKF96365, 2-aminoethyl
      diphenylborate, and MRS1845 and the novel compounds, Synta66 and GSK-7975A. The
      potency of SOCE inhibition was in the order of Synta66>2-aminoethyl
      diphenylborate>GSK-7975A>SKF96365>MRS1845. The specificity of the first 3
      compounds was verified with platelets from Orai1-deficient mice. Inhibitory
      activity on procoagulant activity and high-shear thrombus formation was assessed
      in plasma and whole blood. In the presence of plasma, all 3 compounds suppressed
      platelet responses and restrained thrombus formation under flow. Using a murine
      stroke model, arterial thrombus formation was provoked in vivo by transient
      middle cerebral artery occlusion. Postoperative administration of 2-aminoethyl
      diphenylborate markedly diminished brain infarct size. CONCLUSIONS: Plasma
      soluble SOCE blockers such as 2-aminoethyl diphenylborate suppress platelet
      dependent coagulation and thrombus formation. The platelet Orai1 channel is a
      novel target for preventing thrombotic events causing brain infarction.

PMID- 22580896
TI  - Impact of sphingomyelin synthase 1 deficiency on sphingolipid metabolism and
      atherosclerosis in mice.
AB  - OBJECTIVE: Sphingomyelin synthase (SMS) catalyzes the conversion of ceramide to
      sphingomyelin and sits at the crossroads of sphingolipid biosynthesis. SMS has 2
      isoforms: SMS1 and SMS2. Although they have the same SMS activity, they are
      different enzymes with distinguishable subcellular localizations and cell
      expression patterns. It is conceivable that these differences could yield
      different consequences, in terms of sphingolipid metabolism and its related
      atherogenesis. METHODS AND RESULTS: We created Sms1 gene knockout mice and found
      that Sms1 deficiency significantly decreased plasma, liver, and macrophage
      sphingomyelin (59%, 45%, and 54%, respectively), but only had a marginal effect
      on ceramide levels. Surprisingly, we found that Sms1 deficiency dramatically
      increased glucosylceramide and GM3 levels in plasma, liver, and macrophages (4-
      to 12-fold), whereas Sms2 deficiency had no such effect. We evaluated the total
      SMS activity in tissues and found that Sms1 deficiency causes 77% reduction in
      SMS activity in macrophages, indicating SMS1 is the major SMS in macrophages.
      Moreover, Sms1-deficient macrophages have a significantly higher glucosylceramide
      synthase activity. We also found that Sms1 deficiency significantly attenuated
      toll-like 4 receptor-mediated nuclear factor-kappaB and mitogen-activated protein
      kinase activation after lipopolysaccharide treatment. To evaluate atherogenicity,
      we transplanted Sms1 knockout mouse bone marrow into low-density lipoprotein
      receptor knockout mice (Sms1(-/-)->Ldlr(-/-)). After 3 months on a western diet,
      these animals showed a significant decrease of atherosclerotic lesions in the
      root and the entire aorta (35% and 44%, P<0.01, respectively) and macrophage
      content in lesions (51%, P<0.05), compared with wild-type->Ldlr(-/-) mice.
      CONCLUSIONS: Sms1 deficiency decreases sphingomyelin, but dramatically increases
      the levels of glycosphingolipids. Atherosclerosis in Sms1(-/-)->Ldlr(-/-) mice is
      significantly decreased.

PMID- 22580898
TI  - Leptin potentiates endothelium-dependent relaxation by inducing endothelial
      expression of neuronal NO synthase.
AB  - OBJECTIVE: Obesity is associated with hyperleptinemia but it is not clear whether
      leptin protects vascular function or promotes dysfunction. We therefore studied
      the consequences of hyperleptinemia in lean mice. METHODS AND RESULTS: Wild-type
      and endothelial NO synthase (eNOS)(-/-) mice were infused with leptin (0.4 mg/kg
      per day, 7 days), and endothelium-dependent relaxation was studied in aortic
      segments. Leptin had no effect on acetylcholine-induced endothelium-dependent
      relaxation in normal wild-type mice but restored endothelium-dependent relaxation
      in wild-type mice treated with angiotensin II (0.7 mg/kg per day, 7 days) to
      induce endothelial dysfunction. Leptin also sensitized aortae from eNOS(-/-) mice
      to acetylcholine, an effect blocked by neuronal NOS (nNOS) inhibition and not
      observed in eNOS-nNOS double(-/-) mice. Consistent with these findings, leptin
      induced nNOS expression in murine and human vessels and human endothelial but not
      smooth muscle cells. Aortic nNOS expression was also induced in mice by a high
      fat diet. Mechanistically, leptin increased endothelial Janus kinase 2 and signal
      transducer and activator of transcription 3 phosphorylation, and inhibition of
      Janus kinase 2 prevented nNOS induction in cultured cells and leptin-induced
      relaxations in eNOS(-/-) mice. CONCLUSIONS: Leptin induces endothelial nNOS
      expression, which compensates, in part, for a lack of NO production by eNOS to
      maintain endothelium-dependent relaxation.

PMID- 22580897
TI  - Toll-like receptor 4 deficiency decreases atherosclerosis but does not protect
      against inflammation in obese low-density lipoprotein receptor-deficient mice.
AB  - OBJECTIVE: Obesity is associated with insulin resistance, chronic low-grade
      inflammation, and atherosclerosis. Toll-like receptor 4 (TLR4) participates in
      the cross talk between inflammation and insulin resistance, being activated by
      both lipopolysaccharide and saturated fatty acids. The present study was
      undertaken to determine whether TLR4 deficiency has a protective role in
      inflammation, insulin resistance, and atherosclerosis induced by a diabetogenic
      diet. METHODS AND RESULTS: TLR4 and low-density lipoprotein (LDL) receptor double
      knockout mice and LDL receptor-deficient mice were fed either a normal chow or a
      diabetogenic diet for 24 weeks. TLR4 and LDL receptor double knockout mice fed a
      diabetogenic diet showed improved plasma cholesterol and triglyceride levels but
      developed obesity, hyperinsulinemia, and glucose intolerance equivalent to obese
      LDL receptor-deficient mice. Adipocyte hypertrophy, macrophage accumulation, and
      local inflammation were not attenuated in intraabdominal adipose tissue in TLR4
      and LDL receptor double knockout mice. However, TLR4 deficiency led to markedly
      decreased atherosclerosis in obese TLR4 and LDL receptor double knockout mice.
      Compensatory upregulation of TLR2 expression was observed both in obese TLR4
      deficient mice and in palmitate-treated TLR4-silenced 3T3-L1 adipocytes.
      CONCLUSIONS: TLR4 deficiency decreases atherosclerosis without affecting obesity
      induced inflammation and insulin resistance in LDL receptor-deficient mice.
      Alternative pathways may be responsible for adipose tissue macrophage
      infiltration and insulin resistance that occurs in obesity.

PMID- 22580899
TI  - Proprotein convertase subtilisin/kexin type 9 interacts with apolipoprotein B and
      prevents its intracellular degradation, irrespective of the low-density
      lipoprotein receptor.
AB  - OBJECTIVE: proprotein convertase subtilisin/kexin type 9 (PCSK9) negatively
      regulates the low-density lipoprotein (LDL) receptor (LDLR) in hepatocytes and
      therefore plays an important role in controlling circulating levels of LDL
      cholesterol. To date, the relationship between PCSK9 and metabolism of
      apolipoprotein B (apoB), the structural protein of LDL, has been controversial
      and remains to be clarified. METHODS AND RESULTS: We assessed the impact of PCSK9
      overexpression (~400-fold above baseline) on apoB synthesis and secretion in 3
      mouse models: wild-type C57BL/6 mice and LDLR-null mice (Ldlr(-/-) and Ldlr(-/
      )Apobec1(-/-)). Irrespective of LDLR expression, mice transduced with the PCSK9
      gene invariably exhibited increased levels of plasma cholesterol,
      triacylglycerol, and apoB. Consistent with these findings, the levels of very-low
      density lipoprotein and LDL were also increased whereas high-density lipoprotein
      levels were unchanged. Importantly, we demonstrated that endogenous PCSK9
      interacted with apoB in hepatocytes. The PCSK9/apoB interaction resulted in
      increased production of apoB, possibly through the inhibition of intracellular
      apoB degradation via the autophagosome/lysosome pathway. CONCLUSIONS: We propose
      a new role for PCSK9 that involves shuttling between apoB and LDLR. The present
      study thus provides new insights into the action of PCSK9 in regulating apoB
      metabolism. Furthermore, our results indicate that targeting PCSK9 expression
      represents a new paradigm in therapeutic intervention against hyperlipidemia.

PMID- 22580900
TI  - Liver X receptor agonist modulation of cholesterol efflux in mice with intestine
      specific deletion of microsomal triglyceride transfer protein.
AB  - OBJECTIVE: Previous work demonstrated that intestinal cholesterol absorption and
      regulated expression of intestinal Niemann-Pick C1-like 1 and ATP-binding
      cassette protein A1 are required for liver X receptor (LXR) agonist-mediated
      increases in high-density lipoprotein biogenesis. We re-examined those
      conclusions in mice with intestine-specific deletion of the microsomal
      triglyceride transfer protein (MTTP-IKO), where chylomicron formation is
      eliminated. METHODS AND RESULTS: MTTP-IKO mice demonstrated sustained ~90%
      reduction in cholesterol absorption and >80% reduction in Niemann-Pick C1-like 1
      expression, yet LXR agonist treatment increased serum high-density lipoprotein
      and upregulated intestinal ATP-binding cassette protein A1 expression. Hepatic
      lipogenesis and triglyceride content increased with LXR agonist treatment in both
      genotypes. Biliary cholesterol secretion was increased in MTTP-IKO mice without
      further increase upon LXR agonist administration. LXR agonist treatment caused a
      paradoxical increase in cholesterol absorption in MTTP-IKO mice and decreased
      fecal neutral sterol excretion, but to levels that still exceeded fecal neutral
      sterol excretion in LXR agonist-treated control mice. Finally, MTTP-IKO mice
      demonstrated indistinguishable patterns of increased cholesterol turnover and
      efflux after intravenous radiolabeled cholesterol administration, with or without
      LXR agonist treatment. CONCLUSIONS: Both intestinal and hepatic cholesterol
      efflux pathways are basally upregulated in MTTP-IKO mice. Moreover, LXR-dependent
      pathways modulate intestinal cholesterol absorption, transport, efflux, and high
      density lipoprotein production independent of chylomicron assembly and secretion.

PMID- 22580901
TI  - Voiding urosonography including urethrosonography: high-quality examinations with
      an optimised procedure using a second-generation US contrast agent.
AB  - BACKGROUND: Voiding urosonography (VUS) is established as a technique for
      detecting vesicoureteral reflux in children. OBJECTIVE: To evaluate the quality
      of images of the entire urinary tract when using a second-generation US contrast
      agent and a modified VUS technique. MATERIALS AND METHODS: We evaluated 307 VUS
      examinations performed using SonoVue(r) in 591 pelvi-ureter units in 295 children
      of mean age, 27.1 (S.D., 42.5) months, with 154 (50.2%) of the examinations
      performed in boys; 58 children also underwent VUS using Levovist(r). Three
      criteria were used for quality assessment of the bladder image: (1) progressive
      incorporation of contrast material in the bladder, (2) homogeneous bladder
      filling to maximum capacity, and (3) visualisation of the posterior bladder wall.
      RESULTS: Criterion 1 was fulfilled in 305 (99.3%), criterion 2 in 304 (99%) and
      criterion 3 in 304 (99%) studies. In children who underwent VUS with both
      contrast agents, the concordance between the two techniques was moderate for
      findings in the bladder (Cohen K = 0.487; P < 0001) and perfect for findings in
      the male urethra. CONCLUSION: By a modified technique we obtained high-quality
      images of the bladder with the second-generation contrast agent.

PMID- 22580903
TI  - Obstructive sleep apnea and primary snoring in children with epilepsy.
AB  - Sleep-related breathing disruptions in children with epilepsy are common and can
      range from primary snoring to obstructive sleep apnea. Untreated obstructive
      sleep apnea can lead to significant morbidity. This study aimed to identify
      factors associated with its occurrence and severity in children with epilepsy.
      Children with epilepsy and sleep disruption were evaluated with polysomnography
      and diagnosed with obstructive sleep apnea or primary snoring. Statistical
      analyses were done to identify differences within both the groups and among the
      subjects in the obstructive sleep apnea group. Uncontrolled epilepsy was a risk
      factor for obstructive sleep apnea (80%) compared with primary snoring (47%, P =
      .02). Obstructive index increased with increasing number of antiepileptic drugs.
      In children with epilepsy and disturbed sleep, obstructive sleep apnea is
      associated with uncontrolled epilepsy and is more severe with polytherapy use.
      Children with uncontrolled seizures on antiepileptic polytherapy should be
      routinely screened for obstructive sleep apnea.

PMID- 22580902
TI  - Dietary lysine imbalance affects muscle proteome in zebrafish (Danio rerio): a
      comparative 2D-DIGE study.
AB  - Lysine (Lys) is an indispensable amino acid (AA) and generally the first limiting
      AA in vegetable protein sources in fish feeds. Inadequate dietary Lys
      availability may limit protein synthesis, accretion and growth of fish. This
      experiment aimed to further elucidate the role of Lys imbalance on growth by
      examining the myotomal muscle proteome of juvenile zebrafish (Danio rerio).
      Quadruplicate groups of 8 fish were fed either a low-Lys [Lys(-), 1.34 g kg(-1)],
      medium/control (Lys, 2.47 g kg(-1)) or high-Lys [Lys(+), 4.63 g kg(-1)] diet.
      Fish growth was monitored from 33 to 49 days post-fertilization (dpf) and trunk
      myotomal muscle proteome of Lys(-) and Lys(+) treatments were screened by 2D-DIGE
      and MALDI ToF tandem mass spectrometry. Growth rate was negatively affected by
      diet Lys(-). Out of 527 +/- 11 (mean +/- S.E.M.) protein spots detected (~10-150
      kDa and 4-7 pI value), 30 were over-expressed and 22 under-expressed in Lys(-)
      fish (|fold-change| >1.2, p value <0.05). Higher myosin light chains abundance
      and other myofibrillar proteins in Lys(-) fish pointed to increased sarcomeric
      degradation, indicating a higher protein turnover for supplying basal energy
      saving metabolism rather than growth and muscle protein accretion. The Lys
      deficiency also possibly induced a higher feeding activity, reflected in the over
      expression of beta enolase and mitochondrial ATP synthase. Contrarily, in the
      faster growing fish [Lys(+)], over-expression of apolipoprotein A-I, F-actin
      capping protein and Pdlim7 point to increased energy storage as fat and enhanced
      muscle growth, particularly by mosaic hyperplasia. Thus using an exploratory
      approach, this study pinpoints interesting candidates for further elucidating the
      role of dietary Lys on growth of juvenile fish.

PMID- 22580905
TI  - pH-Induced precipitation behavior of weakly basic compounds: determination of
      extent and duration of supersaturation using potentiometric titration and
      correlation to solid state properties.
AB  - PURPOSE: To examine the precipitation and supersaturation behavior of ten weak
      bases in terms of the relationship between pH-concentration-time profiles and the
      solid state properties of the precipitated material. METHODS: Initially the
      compound was dissolved at low pH, followed by titration with base to induce
      precipitation. Upon precipitation, small aliquots of acid or base were added to
      induce slight subsaturation and supersaturation respectively and the resultant pH
      gradient was determined. The concentration of the unionized species was
      calculated as a function of time and pH using mass and charge balance equations.
      RESULTS: Two patterns of behavior were observed in terms of the extent and
      duration of supersaturation arising following an increase in pH and this behavior
      could be rationalized based on the crystallization tendency of the compound. For
      compounds that did not readily crystallize, an amorphous precipitate was formed
      and a prolonged duration of supersaturation was observed. For compounds that
      precipitated to crystalline forms, the observed supersaturation was short-lived.
      CONCLUSION: This study showed that supersaturation behavior has significant
      correlation with the solid-state properties of the precipitate and that pH-metric
      titration methods can be utilized to evaluate the supersaturation behavior.

PMID- 22580904
TI  - Unimanual and bimanual intensive training in children with hemiplegic cerebral
      palsy and persistence in time of hand function improvement: 6-month follow-up
      results of a multisite clinical trial.
AB  - This study aims to compare in hemiplegic children the effectiveness of intensive
      training (unimanual and bimanual) versus standard treatment in improving hand
      function, assessing the persistence after 6 months. A multicenter, prospective,
      cluster-randomized controlled clinical trial was designed comparing 2 groups of
      children with hemiplegic cerebral palsy, treated for 10 weeks (3 h/d 7 d/wk;
      first with unimanual constraint-induced movement therapy, second with intensive
      bimanual training) with a standard treatment group. Children were assessed before
      and after treatment and at 3 and 6 months postintervention using Quality of Upper
      Extremity Skills Test (QUEST) and Besta Scales. One hundred five children were
      recruited (39 constraint-induced movement therapy, 33 intensive bimanual
      training, 33 standard treatment). Constraint-induced movement therapy and
      intensive bimanual training groups had significantly improved hand function,
      showing constant increase in time. Grasp improved immediately and significantly
      with constraint-induced movement therapy, and with bimanual training grasp
      improved gradually, reaching the same result. In both, spontaneous hand use
      increased in long-term assessment.

PMID- 22580906
TI  - Development of cell lines from the cactophagous insect: Cactoblastis cactorum
      (Lepidoptera: Pyralidae) and their susceptibility to three baculoviruses.
AB  - The unintentional introduction of the cactus moth, Cactoblastis cactorum, a
      successful biological control agent formerly employed in the control of invasive
      prickly pear cactus species (Opuntia spp.) in Australia, Hawaii, South Africa,
      and various Caribbean islands, has posed great concern as to the possible threat
      to native, endangered species of cactus in the southeastern USA as well as with
      the potential to cause a major infestation of commercial and agricultural cactus
      crops in Mexico. A number of control measures have been investigated with varying
      degrees of success including, field exploration for cactus moth-specific
      parasitoids, insecticides, fungal, bacterial, and nematode agents. Current
      tactics used by the USA-Mexico binational program to eradicate cactus moth from
      Mexico and mitigate its westward movement in the USA include host plant removal,
      the manual removal and destruction of egg sticks and infected cacti stems, and
      the Sterile Insect Technique. One other approach not taken until now is the
      development of a cactus moth cell line as a tool to facilitate the investigation
      of baculoviruses as an alternative biocontrol method for the cactus moth.
      Consequently, we established C. cactorum cell lines derived from adult ovarian
      tissue designated as BCIRL-Cc-AM and BCIRL-Cc-JG. The mean cell population
      doubling time was 204.3 and 112 h for BCIRL-Cc-AM and BCIRL-Cc-JG, respectively,
      with weekly medium change, while the doubling time was 176.6 and 192.6 h for
      BCIRL-Cc-AM and BCIRL-Cc-JG, respectively, with a daily change of medium. In
      addition, the daily versus weekly change in medium was reflected in the
      percentage viability with both cell lines showing higher levels with a daily
      medium change. Of the three baculoviruses tested, only the recombinant AcMNPV
      hsp70Red and GmMNPV at a multiplicity of infection (MOI) of 1.0 were able to
      demonstrate significant production of extracellular virus (ECV) in each of the
      cell lines, whereas both cell lines were refractive to an HzSNPV challenge at an
      MOI of 10. In this study, we have demonstrated both the successful development of
      a C. cactorum cell line and its ability to support a complete baculovirus
      infection. The potential is also there to pursue further investigations to
      determine the susceptibility of the cactus moth cell line to other viruses.
      Additionally, the availability of a cactus moth cell line will facilitate the
      analysis of viruses prior to using the more expensive bioassay test. Finally, it
      is hoped with the knowledge presented here that baculoviruses may also be
      considered as an alternative biocontrol method for the cactus moth.

PMID- 22580907
TI  - Strategies to detect interdigital cell death in the frog, Xenopus laevis: T3
      accerelation, BMP application, and mesenchymal cell cultivation.
AB  - Fates of digits in amniotes, i.e., free or webbed digits, are determined by the
      size of programmed interdigital cell death (ICD) area. However, no (or very few)
      cell death has thus far been observed in developing limb buds of non-amniotic
      terrestrial vertebrates including other anuran or urodela amphibians. We
      speculate that the undetectable situation of amphibian ICD is the result of their
      less frequency due to slow developmental speed characteristic to most amphibian
      species. Here, we present three strategies for detecting difficult-to-find ICD in
      the frog, Xenopus laevis. (1) Addition of triiodo-L-thyronine (T(3)) accelerated
      two to three times the limb development and increased two to four times the
      appearance frequency of vital dye-stainable cells in limb buds of the accelerated
      tadpoles (stage 54 to 55). (2) Application of human bone morphogenetic protein-4
      to the autopods of tadpoles at stage 53 to 54 enhanced digital cartilage
      formation and induced vital dye-stainable cells around the enhanced digital
      cartilages within 2 d. (3) In cell culture, T(3) increased the chondrogenic and
      cell death activities of limb mesenchymal cells. The augmentation of both
      activities by T(3) was stronger in the forelimb cells than in the hindlimb cells.
      This situation is well coincided with the limb fates of non-webbed forelimbs and
      webbed hindlimbs in X. laevis adulthood. Collectively, all three approaches
      showed that it become possible to detect X. laevis ICD with appropriate
      strategies.

PMID- 22580908
TI  - A tribute to Richard G. Ham (1932-2011).

PMID- 22580909
TI  - Real-time confocal imaging of trafficking of nestin-expressing multipotent stem
      cells in mouse whiskers in long-term 3-D histoculture.
AB  - We have previously demonstrated that nestin-expressing multipotent hair follicle
      stem cells are located above the hair follicle bulge and can differentiate into
      neurons and other cell types in vitro. The nestin-expressing hair follicle stem
      cells promoted the recovery of pre-existing axons when they were transplanted to
      the severed sciatic nerve or injured spinal cord. We have also previously
      demonstrated that the whisker hair follicle contains nestin-expressing stem cells
      in the dermal papilla (DP) as well as in the bulge area (BA), but that their
      origin is in the BA. In the present study, we established the technique of long
      term Gelfoam(r) histoculture of whiskers isolated from transgenic mice in which
      nestin drives green fluorescent protein (ND-GFP). Confocal imaging was used to
      monitor ND-GFP-expressing stem cells trafficking in real time between the BA and
      DP to determine the fate of the stem cells. It was observed over a 2-week period
      that the stem cells trafficked from the BA toward the DP area and extensively
      grew out onto Gelfoam(r) forming nerve-like structures. This new method of long
      term histoculture of whiskers from ND-GFP mice will enable the extensive study of
      the behavior of nestin-expressing multipotent stem cells of the hair follicle.

PMID- 22580910
TI  - Histopathological changes in Poecilia latipinna male gonad due to Tribulus
      terrestris administration.
AB  - Tribulus terrestris is a traditionally known non-toxic aphrodisiac herb for
      maleness. It was experimented recently to understand the effect and mechanism on
      mono sex production in Poecilia latipinna. It would help to develop a new eco
      friendly way to masculinize P. latipinna, since males have higher commercial
      value than females. The different concentration (100, 150, 200, 250 and 300 mg/L)
      of T. terrestris extract and a control were tested for their effect on sex
      transformation/reversal in P. latipinna by immersing the newly born young ones in
      the respective concentrations for 2 mo. The obtained results indicate that a dose
      dependant masculinization is obtained due to T. terrestris administration, which
      improved the male proportion. Histological results revealed that the testes of
      fish treated with T. terrestris extract contained all stages of spermatogenesis,
      clearly demonstrating that the administration of T. terrestris extract to P.
      latipinna stimulated spermatogenesis. Thus, it is discernible that 0-d-old
      hatchlings of P. latipinna exposed to T. terrestris extract orient/reverse their
      sex more towards maleness besides yielding better growth and spermatogenesis
      which is a mandate for fancy fish industry.

PMID- 22580912
TI  - Molecular typing and antifungal susceptibility of Exophiala isolates from
      patients with cystic fibrosis.
AB  - The black yeast Exophiala dermatitidis is a frequent agent of colonization of the
      lungs of patients with cystic fibrosis (CF). A total of 71 clinical isolates of
      Exophiala from 13 patients were identified at the species level by sequencing the
      internal transcribed spacer (ITS) regions 1 and 2 of the rDNA genes and typed by
      random amplification of polymorphic DNA (RAPD), using two different primers, BG-2
      and ERIC-1. In vitro susceptibility of these isolates to some systemic antifungal
      drugs was investigated using the CLSI method. Almost all the isolates were
      identified as E. dermatitidis, but long-term colonization with the closely
      related species E. phaeomuriformis was observed in one patient. No clustering was
      found according to the geographical origin of the isolates, the isolation date or
      the antifungal susceptibility. Variations were seen in the susceptibility of
      studied isolates to antifungals but most of them exhibited low susceptibility to
      amphotericin B and although some patients were successively colonized by two
      distinct genotypes, most of the isolates were distributed in patient-specific
      clusters. This phenomenon may be due to genomic variations of E. dermatitidis in
      the lung environment of CF patients. These results are typical of colonization of
      the airways of patients by a poorly distributed environmental fungus, which
      occupies particular reservoirs that need to be defined.

PMID- 22580911
TI  - Comparative in vitro efficacies of ethanol-, EDTA- and levofloxacin-based
      catheter lock solutions on eradication of Stenotrophomonas maltophilia biofilms.
AB  - The aim of this study was to compare the in vitro activity of ethanol, EDTA and
      levofloxacin (Levo), alone or in combination, on biofilms of Stenotrophomonas
      maltophilia recovered from patients with catheter-related bloodstream infections
      (CRBSIs) at a university hospital in Argentina. First, 24 and 48 h biofilms were
      formed in microtitre plates and challenged with 25 or 40 % ethanol for 1 h.
      Biofilms, of the 14 local isolates and from the reference strain K279a, were
      eradicated after both treatments as shown by plate counts and the regrowth
      technique. Second, 24 h biofilms of all isolates were established in silicone
      catheter segments and challenged with 25 or 40 % ethanol, Levo (2.5 mg ml(-1)),
      EDTA (30 mg ml(-1)), 25 % ethanol-EDTA or Levo-EDTA for 1, 3 and 24 h. Viable
      counts of biofilms treated for 1 h with 25 or 40 % ethanol or 25 % ethanol-EDTA
      were under the limit of detection. Killing of biofilms by Levo or Levo-EDTA was
      gradual and it was only after 24 h of treatment that no differences could be seen
      between the effects of these catheter lock solutions (CLSs) and those of ethanol
      (P>0.05). Levo-EDTA, in combination, did not act synergistically against
      biofilms. After 24 h of exposure, EDTA did not eradicate biofilms but reduced
      biofilm survival rates to 1-5 %. The effect of the different CLSs on biomass
      reduction, estimated by crystal violet staining, was highly dependent on the
      isolate, and the most effective agents were 25 and 40 % ethanol. Our results
      suggest that when used as a CLS for short periods, ethanol at low concentrations,
      alone or in combination with a chelator, can decontaminate the line from S.
      maltophilia in cases of CRBSI and help, in conjunction with systemic antibiotics,
      in the retention of precious vascular catheters.

PMID- 22580913
TI  - Adhesion to the yeast cell surface as a mechanism for trapping pathogenic
      bacteria by Saccharomyces probiotics.
AB  - Recently, much attention has been given to the use of probiotics as an adjuvant
      for the prevention or treatment of gastrointestinal pathology. The great
      advantage of therapy with probiotics is that they have few side effects such as
      selection of resistant bacteria or disturbance of the intestinal microbiota,
      which occur when antibiotics are used. Adhesion of pathogenic bacteria onto the
      surface of probiotics instead of onto intestinal receptors could explain part of
      the probiotic effect. Thus, this study evaluated the adhesion of pathogenic
      bacteria onto the cell wall of Saccharomyces boulardii and Saccharomyces
      cerevisiae strains UFMG 905, W303 and BY4741. To understand the mechanism of
      adhesion of pathogens to yeast, cell-wall mutants of the parental strain of
      Saccharomyces cerevisiae BY4741 were used because of the difficulty of mutating
      polyploid yeast, as is the case for Saccharomyces cerevisiae and Saccharomyces
      boulardii. The tests of adhesion showed that, among 11 enteropathogenic bacteria
      tested, only Escherichia coli, Salmonella Typhimurium and Salmonella Typhi
      adhered to the surface of Saccharomyces boulardii, Saccharomyces cerevisiae UFMG
      905 and Saccharomyces cerevisiae BY4741. The presence of mannose, and to some
      extent bile salts, inhibited this adhesion, which was not dependent on yeast
      viability. Among 44 cell-wall mutants of Saccharomyces cerevisiae BY4741, five
      lost the ability to fix the bacteria. Electron microscopy showed that the
      phenomenon of yeast-bacteria adhesion occurred both in vitro and in vivo (in the
      digestive tract of dixenic mice). In conclusion, some pathogenic bacteria were
      captured on the surface of Saccharomyces boulardii, Saccharomyces cerevisiae UFMG
      905 and Saccharomyces cerevisiae BY4741, thus preventing their adhesion to
      specific receptors on the intestinal epithelium and their subsequent invasion of
      the host.

PMID- 22580914
TI  - Natural and experimental Helicobacter pullorum infection in Brown Norway rats.
AB  - Helicobacter pullorum is an enterohepatic Helicobacter species (EHS) that was
      recently reported as a naturally acquired infection in mice. Faecal samples from
      18 out of 20 Brown Norway (BN) rats, housed in the same barrier as the H.
      pullorum-infected mice, were positive for H. pullorum using species-specific PCR.
      In addition, we determined whether H. pullorum was able to persistently colonize
      the gastrointestinal tract and/or biliary tree and elicit tissue inflammation as
      well as a serum IgG response in BN rats. Six (four male, two female) 6-week-old,
      H. pullorum-negative BN rats were orally dosed with 4*10(8) c.f.u. of H. pullorum
      every other day for a total of three doses. At 2 weeks post-infection, all rats
      were H. pullorum-positive by faecal PCR. Five out of the six BN rats remained H.
      pullorum-positive for the entire 30 week study. PCR analysis of tissue collected
      at necropsy confirmed that the colon and caecum were the primary sites of H.
      pullorum colonization. Rats that were persistently colonized by H. pullorum had a
      sustained H. pullorum-specific IgG response measured by ELISA. Intestinal or
      hepatic pathology associated with H. pullorum infection was not noted. To our
      knowledge, this is the first report documenting that rats can be persistently
      colonized with an EHS that also infects humans.

PMID- 22580915
TI  - Evidence for the predominance of a single tet(M) gene sequence type in
      tetracycline-resistant Ureaplasma parvum and Mycoplasma hominis isolates from
      Tunisian patients.
AB  - Resistance to tetracyclines in genital mycoplasmas is due mainly to acquisition
      of the tet(M) determinant, which is frequently associated with conjugative
      transposon elements of the Tn916/Tn1545 family. The aim of the present work was
      to evaluate the prevalence of tet(M) in Tunisian isolates and to gain an insight
      into its origin and evolution. Twenty Ureaplasma parvum, two Ureaplasma
      urealyticum and 48 Mycoplasma hominis isolates, recovered from Tunisian patients
      with urogenital and infertility disorders, were evaluated for their resistance to
      tetracyclines and interrogated by PCR amplification for the presence of tet(M)
      and int-Tn, the gene encoding the integrase of Tn916/Tn1545-like transposons. The
      resistance rates to tetracyclines were 22.72 and 25.0 % among U. parvum and M.
      hominis isolates, respectively, with high-level resistance observed in 11 of the
      12 resistant M. hominis isolates. All resistant isolates harboured both tet(M)
      and int-Tn sequences. Nucleotide sequence analysis of the tet(M) amplicon
      revealed a unique sequence shared by all tetracycline-resistant clinical isolates
      of both species. Molecular typing indicated that the tetracycline-resistant U.
      parvum and M. hominis isolates were not clonal. Taken together, these data
      indicate that a single tet(M) gene sequence type, most probably transmitted via a
      Tn916/Tn1545-like transposon, contributes to most of the tetracycline resistance
      in U. parvum and M. hominis isolates in Tunisia. Because this tet(M) gene
      sequence type was harboured by different Mycoplasma spp. and by phylogenetically
      distinct isolates within these species, one could reasonably argue that it may
      have benefited from an efficient horizontal transfer context, making it highly
      competent to spread.

PMID- 22580916
TI  - Carriage of Clostridium difficile in outpatients with irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is a common, typically chronic and sometimes
      disabling gastrointestinal condition of uncertain aetiology. Recently, a variety
      of links to gastrointestinal infections have been described including the onset
      of IBS following exposure to enteric pathogens and an apparent predisposition to
      gastrointestinal infection. The prevalence of Clostridium difficile in a
      population of IBS outpatients (n = 87) in the absence of established risk factors
      for the acquisition of C. difficile infection was examined. Overall, 5.7 % of
      patients (n = 5) carried culturable C. difficile and 4.6 % (n = 4) of isolates
      were toxigenic, belonging to toxinotype group 0, compared with 1.1 % (n = 1) for
      the healthy control group (n = 88). These isolates were members of toxigenic PCR
      ribotype groups 005 and 050 (IBS group) and 062 (control group) and were
      identified further as three individual strains by PFGE. Although no significant
      difference was observed between IBS patients and healthy volunteers, these
      findings support the concept that a subpopulation of IBS patients may be
      susceptible to gastrointestinal infection.

PMID- 22580917
TI  - Life-threatening Escherichia coli cellulitis in patients with haematological
      malignancies.
AB  - Cellulitis due to Escherichia coli is rare and usually secondary to a cutaneous
      portal of entry. Skin and soft tissue infections (SSTI) secondary to E. coli
      bacteraemia have been reported exclusively in immunodeficient patients. Here, we
      report two cases of serious cellulitis secondary to E. coli bacteraemia in
      patients with haematological malignancies. Both isolated strains belonged to
      phylogenetic group B2 and harboured some of the main virulence factor genes
      commonly found in extra-intestinal pathogenic E. coli (ExPEC), including neuC,
      iro and fimH. Cellulitis due to E. coli seems to be linked to the
      immunocompromised status of patients rather than to a highly virulent clone.
      Nevertheless, some of the virulence factors appear to be important because both
      isolates belong to phylogenetic group B2. This aetiology should be considered in
      SSTI in patients with haematological malignancies.

PMID- 22580918
TI  - An indirect reduction technique for ventral stabilization of atlantoaxial
      instability in miniature breed dogs.
AB  - OBJECTIVE: To describe an indirect reduction method for ventral fixation of
      atlantoaxial instability. STUDY: Retrospective study. ANIMALS: Miniature dogs (n
      = 5) with atlanto-axial instability. MATERIALS AND METHODS: For surgery, the
      anaesthetized dogs were positioned in dorsal recumbency. A standard ventral
      midline cranial cervical approach was used. The median part of the cervical (C)
      vertebral bodies of C1, C2 and C3 were exposed. After excision of the
      atlantoaxial joint capsule, a fenestration was performed at the C2-C3
      intervertebral disc with a narrow slot in the ventral cranial endplate of C3. A
      midline incision of the atlanto-occipital membrane at the intercondyloid incisure
      was made to provide access to the spinal canal. Longitudinal distraction and
      realignment of C1-C2 were obtained by placing the tips of a Gelpi retractor in
      the two openings created. Overdistraction allowed removal of articular cartilage
      between C1-C2. Closing of the C1-C2 articular gap was finally achieved by
      applying lateral distraction with a second Gelpi retractor placed between the
      paired longus colli muscles. Fixation could then be performed without further
      stabilization. RESULTS: No intraoperative complications were observed. Recovery
      was uneventful. CONCLUSIONS: The described technique offered good surgical
      visibility and permitted safe reduction of atlantoaxial subluxation. CLINICAL
      RELEVANCE: By reducing manipulation and instrumentation necessary for reduction
      of atlantoaxial instability, the described technique may be advantageous in toy
      breed dogs.

PMID- 22580919
TI  - New half sandwich Ru(II) coordination compounds for anticancer activity.
AB  - With the aim of expanding the structure-activity relationship investigation, the
      series of Ru(II) half sandwich coordination compounds of the type
      [Ru([9]aneS3)(chel)(L)](n+) previously described by us (where [9]aneS3 is the
      neutral face-capping ligand 1,4,7-trithiacyclononane, chel is a neutral or anonic
      chelating ligand, L = Cl(-) or dmso-S, n = 0-2) was extended to 1,4,7
      triazacyclononane ([9]aneN3). In addition, new neutral N-N, and anionic N-O and O
      O chelating ligands, i.e. dach (trans-1,2-diaminocyclohexane), pic(-)
      (picolinate), and acac(-) (acetylacetonate), were investigated in combination
      with both [9]aneS3 and [9]aneN3. Overall, ten new half-sandwich complexes were
      prepared and fully characterized and their chemical behaviour in aqueous solution
      was established. The single-crystal X-ray structures of eight of them, including
      the versatile precursor [Ru([9]aneN3)(dmso-S)(2)Cl]Cl (9), were also determined.
      The results of in vitro antiproliferative tests performed on selected compounds
      against MDA-MB-231 human mammary carcinoma cells confirmed that, in this series,
      only compounds that hydrolyse the monodentate ligand at a reasonable rate show
      moderate activity, provided that the chelate ligand is a hydrogen bond donor.

PMID- 22580920
TI  - Development of a new method for genetic transformation of the green alga
      Chlorella ellipsoidea.
AB  - Chlorella ellipsoidea is a single-celled eukaryotic green microalgae with high
      nutritional value. Its value may be further increased if a simple, reliable and
      cost-effective transformation method for C. ellipsoidea can be developed. In this
      paper, we describe a novel transformation method for C. ellipsoidea . This system
      is based on treatment of C. ellipsoidea cells with cellulolytic enzymes to weaken
      their cell walls, making them become competent to take up foreign DNA. To
      demonstrate the usefulness and effectiveness of this method, we treated C.
      ellipsoidea cells with a cell wall-degrading enzyme, cellulase, followed by
      transformation with plasmid pSP-Ubi-GUS harbouring both the zeocin resistance
      gene and the beta-glucuronidase (GUS) reporter gene that serve as selective
      makers for transformation. Transformants were readily obtained on zeocin
      selection medium, reaching transformation efficiency of 2.25 * 10(3)
      transformants/MUg of plasmid DNA. PCR analysis has also demonstrated the presence
      of the GUS reporter gene in the zeocin-resistant transformants. Histochemical
      assays further showed the expression of the GUS activity in both primary
      transformants and transformants after long-term growth (10 months) with
      antibiotic selection on and off. Availability of a simple and efficient
      transformation system for C. ellipsoidea will accelerate the exploration of this
      microalga for a broader range of biotechnological applications, including its use
      as a biologic factory for the production of high-value human therapeutic
      proteins.

PMID- 22580921
TI  - Twenty-Second Meeting of the European Neurological Society. June 9-12, 2012.
      Prague, Czech Republic.

PMID- 22580922
TI  - Expression of podoplanin in salivary gland adenoid cystic carcinoma and its
      association with distant metastasis and clinical outcomes.
AB  - Distant metastasis is a common cause of mortality in patients with salivary gland
      adenoid cystic carcinoma (SACC). However, presently, the development of distant
      metastasis is unable to be predicted in clinical practice. Recent studies have
      shown that overexpression of podoplanin is associated with metastasis and
      survival in patients with several cancer types. The purpose of the present study
      was to determine whether podoplanin is overexpressed in SACC and whether such
      overexpression is associated with distant metastasis and survival. Podoplanin
      expression was determined using immunohistochemistry (IHC) in tumors from 40 SACC
      patients. The expression status was analyzed in regards to patient
      clinicopathological parameters and survival rates. Overexpression of podoplanin
      was detected in 13 (32.5%) of the 40 tumors. Overexpression was significantly
      associated with disease-free survival (P=0.025) and distant metastasis (P=0.015),
      although it was not associated with recurrence and overall survival. In
      conclusion, podoplanin is overexpressed in a subset of SACCs and may be a
      biomarker predicting distant metastasis in patients with SACC.

PMID- 22580923
TI  - [Recurrent bladder cancer after BCG instillation therapy. Local therapy
      options?].
AB  - Patients with a so-called BCG failure (Bacillus Calmette-Guerin) constitute an
      inhomogeneous group of patients. Patients with BCG recurrence or BCG refractive
      tumors are real BCG failures. Therapeutic options are radical cystectomy and a
      conservative approach, depending on the individual risk of recurrence and
      progression. Intravesical chemotherapy with docetaxel or gemcitabine after BCG
      failure shows some promise whereas second line immunotherapy, the combination of
      BCG and interferon (INF)-alpha, is an effective regimen but results need to be
      confirmed. Device-assisted intravesical strategies, such as mitomycin-EMDA or
      chemohyperthermia are candidates to keep in mind for the near future. Finally,
      cystectomy results in the best disease-specific survival in patients with BCG
      failure.

PMID- 22580924
TI  - Alteration in haematological and biochemical parameters of Catla catla exposed to
      sub-lethal concentration of cypermethrin.
AB  - A 60-day experiment was carried out to study the effect of sub-lethal
      concentration of cypermethrin (1/10th of LC(50)) exposure on haematological and
      biochemical parameters of the Indian major carp, Catla catla fingerlings. Under
      exposure, the total erythrocyte count, total leucocyte count, haemoglobin content
      and haematocrit were decreased. All the studied serum parameters viz. total serum
      protein, albumin, globulin contents and albumin-globulin ratio were significantly
      decreased in cypermethrin-exposed fishes. A marked increase was recorded in
      alanine aminotransferase and aspartate aminotransferase activities in liver,
      whereas lactate dehydrogenase activity of muscle and acetylcholine esterase
      activity in brain were inhibited in cypermethrin-exposed fish. The membrane
      transport enzymes (total adenosine triphosphatase, sodium-potassium adenosine
      triphosphatase and magnesium adenosine triphosphatase) activities were decreased
      significantly in the gills of C. catla exposed to sub-lethal concentration of
      cypermethrin. The present study indicates that sub-lethal exposure of C. catla
      fingerlings to cypermethrin alters the haematological and biochemical parameters.

PMID- 22580925
TI  - Presence of 11-ketotestosterone in pre-differentiated male gonads of Odontesthes
      bonariensis.
AB  - The involvement of androgens during sex differentiation period was investigated
      in the pejerrey Odontesthes bonariensis, by classic biochemical studies and
      gonadal histology. We studied in particular whether the enzyme activities
      involved in 11-oxygenated androgen production were active in a gonadal/peritoneum
      complex (GPC) of very small larvae exposed to masculinizing temperatures previous
      to morphological sex differentiation (5 weeks post-hatching). The GPC was
      incubated with 17-hydroxyprogesterone ((3)H-17P), and the presence of 11-KT as
      major metabolite in early gonads undergoing masculine pathway after temperature
      treatment exposure is reported. 11-KT was identified by thin-layer chromatography
      and high-pressure liquid chromatography. The present results show that 11-KT is
      produced at very early stages of testis development in pejerrey, being this
      androgen one of the main mediators of the masculinization induced by temperature
      treatment at the gonad level.

PMID- 22580926
TI  - Genetic modification of iron metabolism in mice affects the gut microbiota.
AB  - The composition of the gut microbiota is affected by environmental factors as
      well as host genetics. Iron is one of the important elements essential for
      bacterial growth, thus we hypothesized that changes in host iron homeostasis, may
      affect the luminal iron content of the gut and thereby the composition of
      intestinal bacteria. The iron regulatory protein 2 (Irp2) and one of the genes
      mutated in hereditary hemochromatosis Hfe , are both proteins involved in the
      regulation of systemic iron homeostasis. To test our hypothesis, fecal metal
      content and a selected spectrum of the fecal microbiota were analyzed from Hfe-/
      , Irp2-/- and their wild type control mice. Elevated levels of iron as well as
      other minerals in feces of Irp2-/- mice compared to wild type and Hfe-/- mice
      were observed. Interestingly significant variation in the general fecal-bacterial
      population-patterns was observed between Irp2-/- and Hfe-/- mice. Furthermore the
      relative abundance of five species, mainly lactic acid bacteria, was
      significantly different among the mouse lines. Lactobacillus (L.) murinus and L.
      intestinalis were highly abundant in Irp2-/- mice, Enterococcus faecium species
      cluster and a species most similar to Olsenella were highly abundant in Hfe-/-
      mice and L. johnsonii was highly abundant in the wild type mice. These results
      suggest that deletion of iron metabolism genes in the mouse host affects the
      composition of its intestinal bacteria. Further studying the relationship between
      gut microbiota and genetic mutations affecting systemic iron metabolism in human
      should lead to clinical implications.

PMID- 22580927
TI  - Comparison of biogenerically reconstructed and waxed-up complete occlusal
      surfaces with respect to the original tooth morphology.
AB  - OBJECTIVES: Recently, it has become possible to reconstruct complete occlusal
      surfaces using the biogeneric tooth model. This study aimed to mathematically
      assess and compare the morphologic agreement between original morphology and CAD
      reconstructed, waxed-up and CAM partial crowns. MATERIALS AND METHODS: Thirty
      nine intact first permanent molars (39 participants) were included. Impressions,
      bite registrations and three gypsum replicas were made. Preparations for CAD/CAM
      partial crowns were performed and scanned. The restorations were biogenerically
      reconstructed (CEREC(r) v3.80) and milled. Wax-ups of these preparations were
      scanned as well as the milled restorations and original teeth. Discrepancies were
      evaluated by matching the scans with the original morphologies (Match3D, output:
      volume/area, z difference) and by contact patterns. The discrepancies were
      compared between CAD-reconstructions and either wax-ups or milled restorations
      (paired t test, alpha = 0.025 for two multiple tests). RESULTS: The mean
      differences between natural tooth morphology (triangular stabilisation 71.8%) and
      biogeneric reconstructions, wax-ups and milled restorations (triangular
      stabilisation 87.2%) were: 184 +/- 36 MUm (volume/area), 187 +/- 41 MUm (z
      difference); 263 +/- 40 MUm (volume/area), 269 +/- 45 MUm (z difference) and 182
      +/- 40 MUm (volume/area), 184 +/- 41 MUm (z difference). Differences associated
      with biogeneric reconstructions were significantly less than those of wax-ups
      (volume/area and z difference, p < 0.0001), but not significantly different than
      those of milled restorations (p = 0.423 (volume/area), p = 0.110 (z difference)).
      CONCLUSIONS: CAD software enables a closer reconstruction of teeth than do wax
      ups, even when no cusps remain. The milling device is precise enough to transfer
      CAD into the final restoration. CLINICAL RELEVANCE: This study shows that state
      of the art CAD/CAM can effectively produce natural tooth morphology and may be
      ideal for fixed partial dentures.

PMID- 22580928
TI  - On the origin of why static or breakloose friction is larger than kinetic
      friction, and how to reduce it: the role of aging, elasticity and sequential
      interfacial slip.
AB  - We discuss the origin of static friction and show how it can be reduced towards
      kinetic friction by the appropriate design of the sliding system. The basic idea
      is to use  elastically soft solids and apply the external forces in such a way
      that different parts of the contacting interface start to slip at different times
      during the (tangential) loading process. In addition, the local slip must be
      large enough in order to result in a strong drop in the static friction force. We
      illustrate the theoretical predictions with the results of a simple model
      experiment.

PMID- 22580929
TI  - Hyponatremia in a child with Takayasu arteritis: questions.

PMID- 22580931
TI  - Effect of supervised exercise program including balance exercises on the balance
      status and clinical signs in patients with fibromyalgia.
AB  - The objective of this study is to investigate whether the supervised exercise
      program including balance exercises was superior to home exercise programs in
      improving clinical parameters and balance status in patients with FM. Fifty women
      who were diagnosed with primary FM were assigned into supervised exercise group
      (Group 1) and home exercise group (Group 2). Evaluation parameters were clinical
      parameters [pain, number of tender points (NTP), Beck Depression Scale (BDS),
      Fibromyalgia Impact Questionnaire (FIQ)], and parameters associated with balance
      [timed up and go test (TUGT), four square step test (FSST), Berg Balance Scale
      (BBS), Activities-Specific Balance Confidence Scale (ABC), and static balance
      measurements]. Significant differences were determined between all pre- and post
      exercise clinical follow-up parameters at 12th week in Group 1. There was a
      significant difference only in the BDS score between baseline and at the 24th
      week. When the changes in balance parameters in Group 1 were investigated, a
      significant difference was noted at the 12th week in terms of TUGT, FSST, and ABC
      scale scores compared to baseline; however, the significant change maintained
      only in ABC scale at the 24th week compared to baseline. Significant differences
      were noted in all clinical parameters in Group 2 at the 12th week, whereas no
      difference was observed at the 24th week. Evaluation of balance parameters in
      Group 2 at the 12th week revealed significant differences in terms of the TUGT,
      FSST, BBS, and ABC scale scores compared to baseline, whereas 24th week
      evaluation revealed significant differences only in the BBS and ABC scale scores.
      When the two groups were compared, a significant difference was observed in favor
      of Group 2 only for the BBS at the 12th week evaluation. Exercise programs had
      short-term beneficial effects on either clinical signs or dynamic balance.

PMID- 22580932
TI  - Raynaud's phenomenon and vitamin D.
AB  - To our knowledge, there have not been studies to evaluate the effect of vitamin D
      supplementation on Raynaud's phenomenon (RP). To test in a randomized, placebo
      controlled, double blind, and prospective way whether 8 weeks of 600,000 IU
      monthly supplementation of oral vitamin D3 would contribute to improvements in
      RP, 53 patients describing RP were recruited during winter 2010-2011. 42 patients
      were deficient in vitamin D dosage and randomly assigned into either the vitamin
      D group or placebo group. Every 4 weeks (for a total of 3 doses), patients
      received their treatment and answered on a visual analogue scale (VAS) basis
      about their RP. In the vitamin D group, baseline average blood vitamin D level
      was 20.9 ng/mL. VAS 0, VAS 1, and VAS 2 were 58.33, 48.09, and 36.2,
      respectively. At the end of the study, the average blood vitamin D level was 32.9
      ng/mL. In the placebo group, baseline average blood vitamin D level was 21.8
      ng/mL. VAS 0, VAS 1, and VAS 2 were 58.33, 51.19, and 64.28, respectively. At the
      end of the study, the average blood vitamin D level was 23.2 ng/mL. Following our
      observations, we concluded to an objective augmentation of vitamin D blood level
      and RP self-judgment improvement after 8 weeks of monthly supplementation of
      vitamin D3. One can ask whether vitamin D has as a vasodilator effect in patients
      with RP who are deficient in vitamin D. Other studies and researches are needed
      to answer these questions.

PMID- 22580934
TI  - Defining a successful esophagectomy.

PMID- 22580933
TI  - Antitumor activity of MEK and PI3K inhibitors against malignant pleural
      mesothelioma cells in vitro and in vivo.
AB  - Malignant pleural mesothelioma (MPM) is an aggressive malignancy for which there
      is no approved targeted therapy. We examined the therapeutic efficacy of the
      mitogen-activated protein kinase kinase (MEK) and phosphatidylinositol 3-kinase
      (PI3K) inhibitors against human MPM cell lines both in vitro and orthotopically
      inoculated into severe combined immunodeficient (SCID) mice. In addition, the
      molecular mechanisms of these agents were confirmed in vitro and in vivo. The MEK
      or the PI3K inhibitor suppressed MPM cell growth in vitro in a dose-dependent
      manner via induction of G1 cell cycle arrest and apoptosis. In addition, combined
      use of the MEK and PI3K inhibitors showed an additive or synergistic inhibitory
      effect on MPM cell growth compared to treatment with either individual drug.
      Treatment with MEK or PI3K inhibitor suppressed the production of thoracic tumors
      and pleural effusion and prolonged the survival time of EHMES-10 cell-bearing
      SCID mice. The combination therapy more effectively prolonged the survival time
      compared to treatment with either individual drug. Immunohistochemical and
      western blot analysis of thoracic tumors suggested that these agents induced cell
      cycle arrest, apoptosis and inhibition of tumor angiogenesis. Our results suggest
      that a combination of MEK and PI3K inhibitors is a promising therapeutic strategy
      for MPM.

PMID- 22580935
TI  - Prospective, randomized assessment of the acquisition, maintenance, and loss of
      laparoscopic skills.
AB  - BACKGROUND: Laparoscopic skills are difficult to learn. We, therefore, assessed
      the factors involved in skill acquisition, maintenance, and loss in 2
      prospective, randomized studies. METHODS: In study 1, 24 laparoscopic novices
      were randomly assigned to a control condition who performed the laparoscopic
      assessment task; Massed condition who trained on virtual reality (VR) simulation
      during 1 day or Interval condition who had the same amount of VR training
      distributed over 3 consecutive days. All groups also completed a novel
      laparoscopic box-trainer task on 5 consecutive days. In study 2, 16 laparoscopic
      novices were randomly assigned to a Practice or a No-practice condition. All
      subjects were required to train on a VR simulation curriculum for the same
      duration and skill attainment level. The week after completion of training,
      subjects in the Practice condition were allowed 1 complete practice trial on the
      simulator. Both groups completed the same tasks 2 weeks after completion of the
      training. RESULTS: In study 1, the Interval trained group showed the fastest rate
      of learning and on completion of training significantly outperformed both the
      Massed and Control groups (P < 0.0001). In study 2, both groups showed
      significant skills improvement from training trial T1 to T3 (P < 0.0001). The
      subjects in the Practice group maintained or improved their skills at 1 week but
      those in the No practice group showed significant decline of skills at 2 weeks
      after training completion (P < 0.0001). CONCLUSIONS: Laparoscopic skills are
      optimally acquired on an Interval training schedule. They significantly decline
      with 2 weeks of nonuse.

PMID- 22580936
TI  - Cholangiocarcinoma or IgG4-associated cholangitis: how feasible it is to avoid
      unnecessary surgical interventions?
AB  - OBJECTIVE: To evaluate the experience of a tertiary hepatopancreaticobiliary
      (HPB) center in the diagnostic approach and management of patients with suspicion
      of cholangiocarcinoma (CCa), focusing on excluding patients with IgG4-associated
      cholangitis (IAC) from unnecessary major surgical interventions. METHODS: Between
      January 2008 and September 2010, a total number of 152 patients with suspicion of
      CCa underwent evaluation through a HPB multidisciplinary team meeting. Patients
      without tissue diagnosis were managed surgically or medically on the basis of
      probable presence of IAC as underlying pathology. Serology, immunostaining, and
      imaging were reviewed and analyzed according to the HISORt (Histology, Imaging,
      Serology, Other organ involvement, Response to therapy) criteria for IAC.
      RESULTS: Tissue diagnosis during the diagnostic workup was achieved in 104
      patients (68%), whereas the remaining 48 were classified as "highly suspicious
      for CCa" (n = 35) or as "probable IAC" (n = 13). Among 16 "highly suspicious for
      CCa" patients who underwent surgery, pathology revealed 2 patients harboring IAC
      (n = 1) and a benign chronic inflammatory biliary stricture (n = 1),
      respectively. Among the 13 patients with primarily medical management as
      "probable IAC," final diagnosis was CCa (n = 3) and IAC (n = 9), while 1 patient
      had no proven diagnosis. The accuracy of serum IgG4 for diagnosis of IAC reached
      60%. Sensitivity and specificity of immunostaining for IAC in biopsy specimens
      were 56% and 89%, respectively. Imaging features suggesting IAC yielded
      sensitivity, specificity, and accuracy of 75%, 89%, and 83%, respectively.
      Initial imaging was revised at the referral institute in 75% of IAC patients (P =
      0.009), while an isolated stricture (P = 0.038), a biliary mass (P = 0.006), and
      normal pancreas on computed tomography (P = 0.01) were statistically significant
      parameters for distinguishing between CCa and IAC. The mean time for establishing
      a diagnosis of IAC was 12.4 months (range: 2.5-32 months). CONCLUSIONS:
      Differential diagnosis between CCa and IAC mandates high index of suspicion and
      low threshold for referral in high volume institutes. The delayed establishment
      of diagnosis particularly for CCa needs to be balanced versus avoiding
      unnecessary surgery for IAC. Imaging features may be most helpful for optimal
      management.

PMID- 22580937
TI  - Partial pancreaticoduodenectomy can provide cure for duodenal gastrinoma
      associated with multiple endocrine neoplasia type 1.
AB  - OBJECTIVE: To evaluate the outcome of pancreaticoduodenectomy (PD) versus non-PD
      resections for the treatment of gastrinoma in multiple endocrine neoplasia type
      1. BACKGROUND: Gastrinoma in MEN1 is considered a rarely curable disease and its
      management is highly controversial both for timing and extent of surgery.
      METHODS: Clinical characteristics, complications and outcomes of 27 prospectively
      collected MEN1 patients with biochemically proven gastrinoma, who underwent
      surgery, were analyzed with special regard to the gastrinoma type and the initial
      operative procedure. RESULTS: Twenty-two (81%) patients with gastrinoma in MEN1
      had duodenal gastrinomas and 5 patients (19%) had pancreatic gastrinomas. At the
      time of diagnosis, 21 (77%) gastrinomas were malignant (18 duodenal, 3
      pancreatic), but distant metastases were only present in 4 (15%) patients.
      Patients with pancreatic gastrinomas underwent either distal pancreatic
      resections or gastrinoma enucleation with lymphadenectomy, 2 patients also had
      synchronous resections of liver metastases. One of these patients was
      biochemically cured after a median of 136 (77-312) months. Thirteen patients with
      duodenal gastrinomas underwent PD resections (group 1, partial PD [n = 11], total
      PD [n = 2]), whereas 9 patients had no-PD resections (group 2) as initial
      operative procedure. Perioperative morbidity and mortality, including
      postoperative diabetes, differed not significantly between groups (P > 0.5). All
      patients of group 1 and 5 of 9 (55%) patients of group 2 had a negative secretin
      test at hospital discharge. However, after a median follow-up of 136 (3-276)
      months, 12 (92%) patients of group 1 were still normogastrinemic compared to only
      3 of 9 (33%) patients of group 2 (P = 0.023). Three (33%) patients of group 2 had
      to undergo up to 3 reoperations for recurrent or metastatic disease compared to
      none of group 1. CONCLUSIONS: Duodenal gastrinoma in MEN1 should be considered a
      surgically curable disease. PD seems to be the adequate approach to this disease,
      providing a high cure rate and acceptable morbidity compared to non-PD
      resections.

PMID- 22580938
TI  - Human equilibrative nucleoside transporter 1 expression predicts survival of
      advanced cholangiocarcinoma patients treated with gemcitabine-based adjuvant
      chemotherapy after surgical resection.
AB  - OBJECTIVE: The aim of this study was to evaluate whether intratumoral human
      equilibrative nucleoside transporter 1 (hENT1) expression can predict the
      survival of advanced cholangiocarcinoma patients treated with adjuvant
      gemcitabine-based chemotherapy (AGC) after surgical resection. BACKGROUND: There
      have been no reports concerning a useful predictive biomarker in patients with
      cholangiocarcinoma treated with adjuvant gemcitabine chemotherapy. METHODS:
      Intratumoral hENT1 expression was investigated immunohistochemically in 105
      patients with resected advanced cholangiocarcinoma. Relationships between
      intratumoral hENT1 expression and clinicopathological factors were evaluated by
      univariate and multivariate analyses. This study was a retrospective analysis on
      retrospectively collected tissue and data. RESULTS: Fifty-one patients received
      AGC, and 54 did not. High and low intratumoral hENT1 expression was found in 74
      (70%) and 31 patients (30%), respectively. There were no significant differences
      in clinicopathological factors between patients with high hENT1 expression and
      those with low hENT1 expression. Survival patients with high hENT1 expression
      were significantly better than those with low hENT1 expression among patients who
      received AGC (P = 0.008), but not among patients who did not (P = 0.894).
      Moreover, a significant difference in survival between patients who received AGC
      and those who did not was observed among patients with high hENT1 expression (P =
      0.002), but not among patients with low hENT1 expression (P = 0.525).
      Intratumoral hENT1 expression was only an independent predictive factor for
      patients treated with AGC by multivariate analysis (P = 0.027). CONCLUSIONS:
      Intratumoral hENT1 expression may be a potent predictive marker for advanced
      cholangiocarcinoma patients treated with AGC.

PMID- 22580939
TI  - Propranolol induces regression of hemangioma cells through HIF-1alpha-mediated
      inhibition of VEGF-A.
AB  - OBJECTIVE: To investigate the mechanism of propranolol on regression of infantile
      hemangiomas. BACKGROUND: Propranolol has been found to be effective in treatment
      of severe hemangiomas of infancy. However, its mechanism of action is as yet
      unknown. METHODS: Cultured proliferating and involuting hemangioma endothelial
      cells were treated with varying concentrations of propranolol for up to 4 days.
      Analysis was performed using cell viability, migration, and tubulogenesis assays,
      as well as quantitative RT-PCR and flow cytometry. Western blots and ELISA assays
      were used to assess protein expression. RESULTS: Treatment with propranolol led
      to a dose dependent cytotoxic effect in hemangioma endothelial cells with
      decreased cell viability, migration, and tubulogenesis. This cytotoxic effect was
      VEGF (vascular endothelial growth factor) dependent, as demonstrated by decreased
      VEGF, VEGF-R1, and VEGF-R2 production. Decreased signaling through the VEGF
      pathway resulted in downregulation of PI3/Akt and p38/MAPK activity. Decreased
      VEGF activity was mediated through the hypoxia inducible factor (HIF)-1alpha
      pathway but not through NF-kappabeta signaling. CONCLUSIONS: Collectively, these
      data suggest that propranolol exerts its suppressive effects on hemangiomas
      through the HIF-1alpha-VEGF-A angiogenesis axis, with effects mediated through
      the PI3/Akt and p38/MAPK pathways. These findings provide a plausible mechanism
      of action of propranolol on regression of infantile hemangiomas.

PMID- 22580940
TI  - Patient selection for cytoreductive surgery in colorectal peritoneal
      carcinomatosis using serum tumor markers: an observational cohort study.
AB  - OBJECTIVE: There were 2 objectives: first, to investigate how many patients were
      excluded from surgery on the basis of the radiological extent of the peritoneal
      carcinomatosis (PC) or the clinical examination; and second, to develop a score
      based primarily on serum tumor markers (STMs) that could predict short cancer
      specific survival (<12 months). BACKGROUND: Patient selection and prediction of
      prognosis is crucial for successful treatment of colorectal PC. METHODS: All
      patients with colorectal PC referred for cytoreductive surgery and
      intraperitoneal chemotherapy (2005-2008) at Uppsala University hospital were
      included. Patients were divided into 2 groups-nonsurgery and surgery.
      Clinicopathological and laboratory parameters were collected in the surgery
      group. A Corep (COloREctal-Pc) score was developed using hazard ratios from
      histology, hematological status, serial serum tumor markers (STMs), and STM
      changes over time. Sensitivity, specificity, positive predicted value (PPV), and
      negative predicted value (NPV) were calculated in a second validating dataset (n
      = 24) with a survival cutoff of less than 12 months. RESULTS: A total of 107
      patients were included in the study, 42 in the nonsurgery group and 65 in the
      surgery group. In the nonsurgery group, 2 patients were excluded solely on the
      basis of the radiological extent of PC and 7 patients on clinical examination.
      The Corep score ranged from 0 to 18. A score of 6 or more showed a validated
      sensitivity of 80%, specificity 100%, PPV 1.0, and NPV 0.93. CONCLUSIONS:
      Radiological extent of PC was not a main deciding factor for treatment decisions
      and had less impact than the clinical examination. The Corep score identified
      patients with short cancer-specific survival that may not be suitable for
      treatment.

PMID- 22580941
TI  - Reoperation versus clinical recurrence rate after ventral hernia repair.
AB  - OBJECTIVE: To compare the clinical recurrence rate with reoperation rate for
      recurrence after ventral hernia repair. BACKGROUND: Reoperation is often used as
      an outcome measure after ventral hernia repair, but it is unknown whether
      reoperation rate reflects the overall clinical risk for recurrence. METHODS: The
      study cohort was recruited from the Danish Ventral Hernia Database and the Danish
      National Patient Registry during January 1, 2007, to December 31, 2007. Inclusion
      criteria were primary umbilical/epigastric (umb/epi) or incisional hernia repair
      from a regional area of 2 million inhabitants. A prospective clinical follow-up
      was conducted in January 2011 using a validated questionnaire on reoperation and
      possible recurrence. Suspicion of recurrence was the criterion for clinical
      examination. A telephone interview and/or patients' hospital files confirmed
      reoperation. RESULTS: A total of 945 patients were eligible, and 902 patients
      responded to the questionnaire (response rate 95%) with a median postoperative
      follow-up of 41 months (range 0-48 months). The analysis comprised 646 patients
      with umb/epi and 256 patients with incisional hernia repair. Clinical examination
      was required in 241 patients. After umb/epi and incisional hernia repair, the
      cumulative risks of reoperation and overall recurrence (reoperation + clinical)
      were 4% and 15% (fourfold underestimation), and 8% and 37% (fivefold
      underestimation) (P < 0.001), respectively. CONCLUSIONS: Reoperation rate for
      recurrence 41 months after primary umbilical/epigastric or incisional hernia
      repair underestimated overall risk of recurrence by four- to fivefolds. This
      study was registered in www.clinicaltrials.gov (NCT01325246).

PMID- 22580942
TI  - Progression following neoadjuvant systemic chemotherapy may not be a
      contraindication to a curative approach for colorectal carcinomatosis.
AB  - OBJECTIVE: The objective of this retrospective study was to evaluate the
      influence of neoadjuvant systemic chemotherapy on patients with colorectal
      carcinomatosis before a curative procedure. BACKGROUND: Peritoneal carcinomatosis
      (PC) from colorectal cancer may be treated with a curative intent by
      cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy
      (HIPEC). The role of perioperative systemic chemotherapy for this particular
      metastatic disease remains unclear. METHODS: One hundred twenty patients with PC
      from colorectal cancer were consecutively treated by 131 procedures combining CRS
      with HIPEC. The response to neoadjuvant systemic chemotherapy was assessed on
      data from previous explorative surgery and/or radiological imaging. RESULTS:
      Ninety patients (75%) were treated with neoadjuvant systemic chemotherapy in whom
      32 (36%) were considered to have responded, 19 (21%) had stable disease, and 19
      (21%) developed diseases progression. Response could not be evaluated in 20
      patients (22%). On univariate analysis, the use of neoadjuvant systemic
      chemotherapy had a significant positive prognostic influence (P = 0.042). On
      multivariate analysis, the completeness of CRS and the use of adjuvant systemic
      chemotherapy were the only significant prognostic factors (P < 0.001 and P =
      0.049, respectively). Response to neoadjuvant systemic chemotherapy had no
      significant prognostic impact with median survival of 31.4 months in patients
      showing disease progression. CONCLUSIONS: In patients with PC from colorectal
      cancer without extraperitoneal metastases, failure of neoadjuvant systemic
      chemotherapy should not constitute an absolute contraindication to a curative
      procedure combining CRS and HIPEC.

PMID- 22580943
TI  - Factors predictive of 30-day postoperative mortality in HIV/AIDS patients in the
      era of highly active antiretroviral therapy.
AB  - BACKGROUND: Factors that predict HIV (human immunodeficiency virus)/AIDS patient
      postoperative mortality have remained poorly defined. OBJECTIVES: The primary
      objective of this study was to identify factors predictive of short-term,
      postoperative mortality in HIV/AIDS patients. The secondary objective of this
      study was to develop a scoring system that would predict short-term postoperative
      mortality in HIV/AIDS patients. METHODS: We retrospectively reviewed all HIV/AIDS
      patients who underwent surgical procedures in British Columbia, Canada, between
      April 1995 and March 2002. The primary outcome evaluated was 30-day postoperative
      mortality. Demographic, clinical, and hospitalization-related data were obtained
      and utilized to predict outcomes using a logistic regression model. RESULTS: A
      total of 2305 procedures were carried out on 1322 patients during the study
      period. Admissions were classified as urgent/emergent for 1311 procedures (57%)
      and the overall 30-day postoperative mortality was 9.5% (126 deaths).
      Urgent/emergent admission, older age, prior surgery, a CD4 cell count of <= 50
      cells/mm, a hemoglobin level <= 120 g/L, and a white blood cell count >11 g/L
      within 90 days before the surgical procedure was predictive of an increased 30
      day postoperative mortality in a multivariate model. Using these variables, we
      formulated the HIV Surgical Mortality Score (HSMS) to obtain the median-estimated
      probability of postoperative death. CONCLUSIONS: For accurate preoperative
      mortality risk stratification for HIV/AIDS patients, we have found that several
      clinical and laboratory variables must be evaluated. If appropriately validated,
      our proposed HSMS could be utilized to estimate the probability of short-term
      postoperative death among HIV/AIDS patients.

PMID- 22580944
TI  - A randomized, controlled, double-blind crossover study on the effects of 2-L
      infusions of 0.9% saline and plasma-lyte(r) 148 on renal blood flow velocity and
      renal cortical tissue perfusion in healthy volunteers.
AB  - OBJECTIVE: We compared the effects of intravenous infusions of 0.9% saline ([Cl]
      154 mmol/L) and Plasma-Lyte 148 ([Cl] 98 mmol/L, Baxter Healthcare) on renal
      blood flow velocity and perfusion in humans using magnetic resonance imaging
      (MRI). BACKGROUND: Animal experiments suggest that hyperchloremia resulting from
      0.9% saline infusion may affect renal hemodynamics adversely, a phenomenon not
      studied in humans. METHODS: Twelve healthy adult male subjects received 2-L
      intravenous infusions over 1 hour of 0.9% saline or Plasma-Lyte 148 in a
      randomized, double-blind manner. Crossover studies were performed 7 to 10 days
      apart. MRI scanning proceeded for 90 minutes after commencement of infusion to
      measure renal artery blood flow velocity and renal cortical perfusion. Blood was
      sampled and weight recorded hourly for 4 hours. RESULTS: Sustained hyperchloremia
      was seen with saline but not with Plasma-Lyte 148 (P < 0.0001), and fall in
      strong ion difference was greater with the former (P = 0.025). Blood volume
      changes were identical (P = 0.867), but there was greater expansion of the
      extravascular fluid volume after saline (P = 0.029). There was a significant
      reduction in mean renal artery flow velocity (P = 0.045) and renal cortical
      tissue perfusion (P = 0.008) from baseline after saline, but not after Plasma
      Lyte 148. There was no difference in concentrations of urinary neutrophil
      gelatinase-associated lipocalin after the 2 infusions (P = 0.917). CONCLUSIONS:
      This is the first human study to demonstrate that intravenous infusion of 0.9%
      saline results in reductions in renal blood flow velocity and renal cortical
      tissue perfusion. This has implications for intravenous fluid therapy in
      perioperative and critically ill patients. NCT01087853.

PMID- 22580945
TI  - Trauma center quality improvement programs in the United States, Canada, and
      Australasia.
AB  - OBJECTIVE: To compare quality improvement (QI) programs of trauma centers in 4
      high-income countries. BACKGROUND: Injury is a leading cause of morbidity and
      mortality in countries around the world, but patient outcomes vary among
      countries with similar systems of trauma care. METHODS: We surveyed medical
      directors and program managers from 330 trauma centers verified by professional
      trauma organizations in the United States (n = 263), Canada (n = 46), and
      Australasia (Australia, n = 18; New Zealand, n = 3) regarding their QI programs.
      Quality indicators were requested from all centers that measured quality of care.
      Follow-up interviews were performed with 75 centers purposively sampled across 6
      baseline criteria. RESULTS: A total of 251 centers (76% response rate) responded
      to the survey, with a similar distribution across countries. Trauma centers in
      the United States were more likely than those in Canada and Australasia to report
      measuring quality indicators (100% vs 94% vs 93%, P = 0.008), using report cards
      (53% vs 33% vs 31%, P = 0.033) and benchmarking (81% vs 61% vs 69%, P = 0.019).
      Centers in all 3 regions primarily used hospital process and outcome measures
      designed to establish whether care was safe (98% vs 97% vs 75%, P = 0.008),
      effective (97% vs 97% vs 92% P = 0.399), timely (88% vs 100% vs 92%, P = 0.055),
      and efficient (95% vs 100% vs 83%, P = 0.082). QI programs were largely local in
      nature, used different criteria to identify patients under QI purview, and
      employed diverse quality indicators and improvement strategies. Few centers
      evaluated the effectiveness of their QI program. CONCLUSIONS: This study provides
      the first international comparison of trauma center QI programs and demonstrates
      broad implementation in verified trauma centers in the United States, Canada, and
      Australasia. Significant variation exists in how trauma centers perform QI
      activities. Opportunities exist for improving and standardizing QI processes.

PMID- 22580946
TI  - Identification of a subgroup of patients at highest risk for complications after
      surgical cytoreduction and hyperthermic intraperitoneal chemotherapy.
AB  - OBJECTIVE: To assess the influence of parietal and visceral peritonectomy
      procedures on moderate/severe morbidity in patients undergoing surgical
      cytoreducion and hyperthermic intraperitoneal chemotherapy (HIPEC) and to
      identify subgroups of patients at highest operative risk. BACKGROUND:
      Cytoreducion with HIPEC is an effective but potentially morbid treatment option
      for peritoneal surface malignancies. Although complication rates have recently
      decreased with increasing experience, risk-factors for adverse operative outcome
      are still poorly understood. METHODS: A prospective database of 426 combined
      procedures was reviewed. Multivariate analysis tested the correlation between
      major morbidity and 6 peritonectomies (greater and lesser omentectomy, pelvic,
      parietal anterior, left and right diaphragmatic peritonectomy), 14 visceral
      resections, 5 other operative factors, and 12 clinical variables. The extent of
      peritoneal involvement was quantified by peritoneal cancer index (PCI). RESULTS:
      Mortality and major morbidity were 2.6% and 28.2%. PCI, number of visceral
      resections, poor performance status, and cisplatin dose more than 240 mg
      independently correlated to morbidity. The type and number of parietal
      peritonectomies and the type of visceral resections did not correlated to
      complications. Major morbidity rate was 65.7% in 35 (8.2%) patients with at least
      2 of the following factors: PCI greater than 30, more than 5 visceral resections,
      poor performance status. Morbidity was 100% in 9 patients presenting all the risk
      factors. CONCLUSIONS: Acceptable morbidity and low mortality may be achieved in
      high-volume centers. Operative outcome is mainly affected by a complex interplay
      of tumor, patient, and treatment-related factors. Preoperative and early
      intraoperative assessment of operative risk may identify a subset of patients
      unlikely to tolerate aggressive management.

PMID- 22580947
TI  - Controlled solvothermal synthesis of novel organic functionalized
      polyoxovanadates.
AB  - Four novel organic functionalized polyoxovanadates are solvothermally synthesized
      by altering the reaction temperature and using different organoarsonic acids.
      These POVs are fully characterized and the phase transitions between different
      POVs structures are confirmed by X-ray diffraction analyses. Such a transition is
      temperature-dependent and thus controlled synthesis of new POVs can be achieved.

PMID- 22580948
TI  - Confocal scanning laser ophthalmoscope in the retromode imaging modality in
      exudative age-related macular degeneration.
AB  - PURPOSE: To evaluate the ability of confocal scanning laser ophthalmoscope (cSLO)
      in the retromode imaging modality in detecting retinal changes secondary to
      exudative age-related macular degeneration (AMD). METHODS: Seventeen eyes of 13
      consecutive patients affected by CNV secondary to AMD were evaluated with optical
      coherence tomography (OCT) to detect neuroretinal detachment (NRD), pigment
      epithelial detachment (PED), cystoid macular edema (CME), and epiretinal
      membranes (ERM). All eyes were examined with a cSLO equipped with infrared
      retromode (RM) imaging modality. Infrared and fundus autofluorescence images were
      also obtained (IR and FAF). The intermethod agreement between OCT and cSLO was
      evaluated considering single cSLO imaging modality separately (IR, FAF, and RM),
      and all imaging modalities together. RESULTS: Eight eyes (47 %) had NRD at OCT;
      intermethod agreement was poor for any single cSLO imaging modality considered
      separately (k: 0.14, 0.01, and 0.29 for cSLO IR, FAF, and RM, respectively). Four
      eyes had PED at OCT (24 %); intermethod agreement was mild for cSLO RM, poor for
      IR and FAF (k: 0.51, 0.16, and 0.00, respectively). CME was present in eight eyes
      (47 %); intermethod agreement was excellent for cSLO RM, poor for IR and FAF (k:
      0.88, 0.38, and 0.26, respectively). ERM was present in three eyes (18 %);
      intermethod agreement was mild for cSLO IR, poor for FAF, and excellent for RM
      (k: 0.59, 0.00, and 0.76, respectively). CONCLUSIONS: cSLO RM imaging is a useful
      and reproducible technique in detecting retinal features associated with CNV,
      particularly CME.

PMID- 22580949
TI  - Waves on Reissner's membrane: a mechanism for the propagation of otoacoustic
      emissions from the cochlea.
AB  - Sound is detected and converted into electrical signals within the ear. The
      cochlea not only acts as a passive detector of sound, however, but can also
      produce tones itself. These otoacoustic emissions are a striking manifestation of
      the cochlea's mechanical active process. A controversy remains of how these
      mechanical signals propagate back to the middle ear, from which they are emitted
      as sound. Here, we combine theoretical and experimental studies to show that
      mechanical signals can be transmitted by waves on Reissner's membrane, an elastic
      structure within the cochlea. We develop a theory for wave propagation on
      Reissner's membrane and its role in otoacoustic emissions. Employing a scanning
      laser interferometer, we measure traveling waves on Reissner's membrane in the
      gerbil, guinea pig, and chinchilla. The results are in accord with the theory and
      thus support a role for Reissner's membrane in otoacoustic emissions.

PMID- 22580950
TI  - Genome sequence of foxtail millet (Setaria italica) provides insights into grass
      evolution and biofuel potential.
AB  - Foxtail millet (Setaria italica), a member of the Poaceae grass family, is an
      important food and fodder crop in arid regions and has potential for use as a
      C(4) biofuel. It is a model system for other biofuel grasses, including
      switchgrass and pearl millet. We produced a draft genome (~423 Mb) anchored onto
      nine chromosomes and annotated 38,801 genes. Key chromosome reshuffling events
      were detected through collinearity identification between foxtail millet, rice
      and sorghum including two reshuffling events fusing rice chromosomes 7 and 9, 3
      and 10 to foxtail millet chromosomes 2 and 9, respectively, that occurred after
      the divergence of foxtail millet and rice, and a single reshuffling event fusing
      rice chromosome 5 and 12 to foxtail millet chromosome 3 that occurred after the
      divergence of millet and sorghum. Rearrangements in the C(4) photosynthesis
      pathway were also identified.

PMID- 22580952
TI  - The challenge of erectile dysfunction in the man with chronic prostatitis/chronic
      pelvic pain syndrome.
AB  - Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), also known as NIH
      category III prostatitis, is common and has significant impact on quality of life
      through pain and lower urinary tract symptoms. A high proportion of men with
      CP/CPPS suffer from some form of sexual dysfunction including erectile
      dysfunction, premature ejaculation, and painful ejaculation. While well
      described, the pathophysiology of these sexual symptoms has not been well
      studied. This review will focus on what we know regarding the incidence and
      potential mechanisms for sexual dysfunction in CP/CPPS and discuss diagnostic and
      therapeutic options.

PMID- 22580953
TI  - A computer-controlled near-field electrospinning setup and its graphic user
      interface for precision patterning of functional nanofibers on 2D and 3D
      substrates.
AB  - Electrospinning is a versatile technique for production of nanofibers. However,
      it lacks the precision and control necessary for fabrication of nanofiber-based
      devices. The positional control of the nanofiber placement can be dramatically
      improved using low-voltage near-field electrospinning (LV-NFES). LV-NFES allows
      nanofibers to be patterned on 2D and 3D substrates. However, use of NFES requires
      low working distance between the electrospinning nozzle and substrate, manual jet
      initiation, and precise substrate movement to control fiber deposition.
      Environmental factors such as humidity also need to be controlled. We developed a
      computer-controlled automation strategy for LV-NFES to improve performance and
      reliability. With this setup, the user is able to control the relevant sensor and
      actuator parameters through a custom graphic user interface application
      programmed on the C#.NET platform. The stage movement can be programmed as to
      achieve any desired nanofiber pattern and thickness. The nanofiber generation
      step is initiated through a software-controlled linear actuator. Parameter
      setting files can be saved into an Excel sheet and can be used subsequently in
      running multiple experiments. Each experiment is automatically video recorded and
      stamped with the pertinent real-time parameters. Humidity is controlled with +/
      3% accuracy through a feedback loop. Further improvements, such as real-time
      droplet size control for feed rate regulation are in progress.

PMID- 22580954
TI  - A gain-of-function mutation in IAA16 confers reduced responses to auxin and
      abscisic acid and impedes plant growth and fertility.
AB  - Auxin regulates many aspects of plant development, in part, through degradation
      of the Aux/IAA family of transcriptional repressors. Consequently, stabilizing
      mutations in several Aux/IAA proteins confer reduced auxin responsiveness.
      However, of the 29 apparent Aux/IAA proteins in Arabidopsis thaliana, fewer than
      half have roles established through mutant analysis. We identified iaa16-1, a
      dominant gain-of-function mutation in IAA16 (At3g04730), in a novel screen for
      reduced root responsiveness to abscisic acid. The iaa16-1 mutation also confers
      dramatically reduced auxin responses in a variety of assays, markedly restricts
      growth of adult plants, and abolishes fertility when homozygous. We compared
      iaa16-1 phenotypes with those of dominant mutants defective in the closely
      related IAA7/AXR2, IAA14/SLR, and IAA17/AXR3, along with the more distantly
      related IAA28, and found overlapping but distinct patterns of developmental
      defects. The identification and characterization of iaa16-1 provides a fuller
      understanding of the IAA7/IAA14/IAA16/IAA17 clade of Aux/IAA proteins and the
      diverse roles of these repressors in hormone response and plant development.

PMID- 22580955
TI  - De novo transcriptome sequencing of Momordica cochinchinensis to identify genes
      involved in the carotenoid biosynthesis.
AB  - The ripe fruit of Momordica cochinchinensis Spreng, known as gac, is featured by
      very high carotenoid content. Although this plant might be a good resource for
      carotenoid metabolic engineering, so far, the genes involved in the carotenoid
      metabolic pathways in gac were unidentified due to lack of genomic information in
      the public database. In order to expedite the process of gene discovery, we have
      undertaken Illumina deep sequencing of mRNA prepared from aril of gac fruit. From
      51,446,670 high-quality reads, we obtained 81,404 assembled unigenes with average
      length of 388 base pairs. At the protein level, gac aril transcripts showed about
      81.5% similarity with cucumber proteomes. In addition 17,104 unigenes have been
      assigned to specific metabolic pathways in Kyoto Encyclopedia of Genes and
      Genomes, and all of known enzymes involved in terpenoid backbones biosynthetic
      and carotenoid biosynthetic pathways were also identified in our library. To
      analyze the relationship between putative carotenoid biosynthesis genes and
      alteration of carotenoid content during fruit ripening, digital gene expression
      analysis was performed on three different ripening stages of aril. This study has
      revealed putative phytoene synthase, 15-cis-phytone desaturase, zeta-carotene
      desaturase, carotenoid isomerase and lycopene epsilon cyclase might be key
      factors for controlling carotenoid contents during aril ripening. Taken together,
      this study has also made availability of a large gene database. This unique
      information for gac gene discovery would be helpful to facilitate functional
      studies for improving carotenoid quantities.

PMID- 22580956
TI  - Alkane biodegradation genes from chronically polluted subantarctic coastal
      sediments and their shifts in response to oil exposure.
AB  - Although sediments are the natural hydrocarbon sink in the marine environment,
      the ecology of hydrocarbon-degrading bacteria in sediments is poorly understood,
      especially in cold regions. We studied the diversity of alkane-degrading
      bacterial populations and their response to oil exposure in sediments of a
      chronically polluted Subantarctic coastal environment, by analyzing alkane
      monooxygenase (alkB) gene libraries. Sequences from the sediment clone libraries
      were affiliated with genes described in Proteobacteria and Actinobacteria, with
      67 % amino acid identity in average to sequences from isolated microorganisms.
      The majority of the sequences were most closely related to uncultured
      microorganisms from cold marine sediments or soils from high latitude regions,
      highlighting the role of temperature in the structuring of this bacterial guild.
      The distribution of alkB sequences among samples of different sites and years,
      and selection after experimental oil exposure allowed us to identify ecologically
      relevant alkB genes in Subantarctic sediments, which could be used as biomarkers
      for alkane biodegradation in this environment. 16 S rRNA amplicon pyrosequencing
      indicated the abundance of several genera for which no alkB genes have yet been
      described (Oleispira, Thalassospira) or that have not been previously associated
      with oil biodegradation (Spongiibacter-formerly Melitea-, Maribius,
      Robiginitomaculum, Bizionia and Gillisia). These genera constitute candidates for
      future work involving identification of hydrocarbon biodegradation pathway genes.

PMID- 22580958
TI  - HMGB1 in development and diseases of the central nervous system.
AB  - High mobility group box 1 (HMGB1) is widely expressed in cells of vertebrates in
      two forms: a nuclear "architectural" factor and a secreted inflammatory factor.
      During early brain development, HMGB1 displays a complex temporal and spatial
      distribution pattern in the central nervous system. It facilitates neurite
      outgrowth and cell migration critical for processes, such as forebrain
      development. During adulthood, HMGB1 serves to induce neuroinflammation after
      injury, such as lesions in the spinal cord and brain. Receptor for advanced
      glycation end products and Toll-like receptors signal transduction pathways
      mediate HMGB1-induced neuroinflammation and necrosis. Increased levels of
      endogenous HMGB1 have also been detected in neurodegenerative diseases. However,
      in Huntington's disease, HMGB1 has been reported to protect neurons through
      activation of apurinic/apyrimidinic endonuclease and 5'-flap endonuclease-1,
      whereas in other neurodegenerative diseases, such as Alzheimer's disease,
      Parkinson's disease, and multiple sclerosis, HMGB1 serves as a risk factor for
      memory impairment, chronic neurodegeneration, and progression of
      neuroinflammation. Thus, HMGB1 plays important and double-edged roles during
      neural development and neurodegeneration. The HMGB1-mediated pathological
      mechanisms have remained largely elusive. Knowledge of these mechanisms is likely
      to lead to therapeutic targets for neurological diseases.

PMID- 22580960
TI  - Stifle arthrodesis in two cats.
AB  - Two Domestic Shorthaired cats were admitted after sustaining multiligamentous
      injuries of the stifle joint. In one cat, prosthetic ligamentous reconstruction
      was unsuccessful at maintaining normal stifle stability. Both cats were treated
      with stifle arthrodesis using internal fixation with a plate and screws without
      external coaptation. In one case, arthrodesis was achieved using a 2.7 mm 16-hole
      dynamic compression plate placed medially. In the second case, a 2.7 mm 14-hole
      dynamic compression plate was placed cranially. No major complications were
      noted, and both cats were able to return to good levels of activity in the medium
      term.

PMID- 22580957
TI  - Auxin and ABA act as central regulators of developmental networks associated with
      paradormancy in Canada thistle (Cirsium arvense).
AB  - Dormancy in underground vegetative buds of Canada thistle, an herbaceous
      perennial weed, allows escape from current control methods and contributes to its
      invasive nature. In this study, ~65 % of root sections obtained from greenhouse
      propagated Canada thistle produced new vegetative shoots by 14 days post
      sectioning. RNA samples obtained from sectioned roots incubated 0, 24, 48, and 72
      h at 25 degrees C under 16:8 h light-dark conditions were used to construct four
      MID-tagged cDNA libraries. Analysis of in silico data obtained using Roche 454 GS
      FLX pyrosequencing technologies identified molecular networks associated with
      paradormancy release in underground vegetative buds of Canada thistle. Sequencing
      of two replicate plates produced ~2.5 million ESTs with an average read length of
      362 bases. These ESTs assembled into 67358 unique sequences (21777 contigs and
      45581 singlets) and annotation against the Arabidopsis database identified 15232
      unigenes. Among the 15232 unigenes, we identified processes enriched with
      transcripts involved in plant hormone signaling networks. To follow-up on these
      results, we examined hormone profiles in roots, which identified changes in
      abscisic acid (ABA) and ABA metabolites, auxins, and cytokinins post-sectioning.
      Transcriptome and hormone profiling data suggest that interaction between auxin-
      and ABA-signaling regulate paradormancy maintenance and release in underground
      adventitious buds of Canada thistle. Our proposed model shows that sectioning
      induced changes in polar auxin transport alters ABA metabolism and signaling,
      which further impacts gibberellic acid signaling involving interactions between
      ABA and FUSCA3. Here we report that reduced auxin and ABA-signaling, in
      conjunction with increased cytokinin biosynthesis post-sectioning supports a
      model where interactions among hormones drives molecular networks leading to cell
      division, differentiation, and vegetative outgrowth.

PMID- 22580959
TI  - Deregulation of BRCA1 leads to impaired spatiotemporal dynamics of gamma-H2AX and
      DNA damage responses in Huntington's disease.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder of
      mid-life onset characterized by involuntary movements and progressive cognitive
      decline caused by a CAG repeat expansion in exon 1 of the Huntingtin (Htt) gene.
      Neuronal DNA damage is one of the major features of neurodegeneration in HD, but
      it is not known how it arises or relates to the triplet repeat expansion mutation
      in the Htt gene. Herein, we found that imbalanced levels of non-phosphorylated
      and phosphorylated BRCA1 contribute to the DNA damage response in HD. Notably,
      nuclear foci of gamma-H2AX, the molecular component that recruits various DNA
      damage repair factors to damage sites including BRCA1, were deregulated when DNA
      was damaged in HD cell lines. BRCA1 specifically interacted with gamma-H2AX via
      the BRCT domain, and this association was reduced in HD. BRCA1 overexpression
      restored gamma-H2AX level in the nucleus of HD cells, while BRCA1 knockdown
      reduced the spatiotemporal propagation of gamma-H2AX foci to the nucleoplasm. The
      deregulation of BRCA1 correlated with an abnormal nuclear distribution of gamma
      H2AX in striatal neurons of HD transgenic (R6/2) mice and BRCA1(+/-) mice. Our
      data indicate that BRCA1 is required for the efficient focal recruitment of gamma
      H2AX to the sites of neuronal DNA damage. Taken together, our results show that
      BRCA1 directly modulates the spatiotemporal dynamics of gamma-H2AX upon genotoxic
      stress and serves as a molecular maker for neuronal DNA damage response in HD.

PMID- 22580951
TI  - Reference genome sequence of the model plant Setaria.
AB  - We generated a high-quality reference genome sequence for foxtail millet (Setaria
      italica). The ~400-Mb assembly covers ~80% of the genome and >95% of the gene
      space. The assembly was anchored to a 992-locus genetic map and was annotated by
      comparison with >1.3 million expressed sequence tag reads. We produced more than
      580 million RNA-Seq reads to facilitate expression analyses. We also sequenced
      Setaria viridis, the ancestral wild relative of S. italica, and identified
      regions of differential single-nucleotide polymorphism density, distribution of
      transposable elements, small RNA content, chromosomal rearrangement and
      segregation distortion. The genus Setaria includes natural and cultivated species
      that demonstrate a wide capacity for adaptation. The genetic basis of this
      adaptation was investigated by comparing five sequenced grass genomes. We also
      used the diploid Setaria genome to evaluate the ongoing genome assembly of a
      related polyploid, switchgrass (Panicum virgatum).

PMID- 22580962
TI  - Acupuncture for postdural puncture headache: report of two cases.

PMID- 22580963
TI  - Drug-induced acute psychosis in an adolescent first-time user of 4-HO-MET.

PMID- 22580961
TI  - Substrate metabolism during basal and hyperinsulinemic conditions in adolescents
      and young-adults with Barth syndrome.
AB  - BACKGROUND: Barth syndrome (BTHS) is a rare X-linked disorder that is
      characterized by mitochondrial abnormalities, infantile or childhood onset of
      cardioskeletal myopathy, and high mortality rates. It is currently unknown if
      BTHS related mitochondrial dysfunction results in substrate metabolism
      abnormalities and thereby contributes to cardioskeletal myopathy in patients with
      BTHS. METHODS: Adolescents and young adults with BTHS (n = 5, 20 +/- 4 yrs) and
      age and activity matched healthy controls (n = 5, 18 +/- 4 yrs) underwent an
      hyperinsulinemic-euglycemic clamp procedure with stable isotopically labeled
      tracers for measurement of lipolysis, fatty acid oxidation, glucose disposal, and
      whole-body proteolysis rates; dual energy x-ray absorptiometry for measurement of
      body composition and 2-D and strain echocardiography for measurement of left
      ventricular function. RESULTS: Participants with BTHS had lower fat-free mass
      (FFM) (BTHS: 31.4 +/- 6.9 vs. CONTROL: 46.7 +/- 5.3 kg, p < 0.005), lower
      systolic function (strain, BTHS: -15.2 +/- 2.4 vs. CONTROL: -19.0 +/- 2.4 %, p <
      0.05), greater insulin-stimulated glucose disposal rate per kg FFM (BTHS: 96.5 +/
      16.3 vs. CONTROL: 67.4 +/- 17.6 MUmol/kgFFM/min, p < 0.05), lower basal (BTHS:
      4.6 +/- 2.7 vs. CONTROL: 11.9 +/- 4.4 MUmol/kgFM/min, p < 0.05) and
      hyperinsulinemic (BTHS: 1.6 +/- 0.4 vs. CONTROL: 3.6 +/- 1.6 MUmol/kgFM/min, p <
      0.05) lipolytic rate per kg fat mass (FM), and a trend towards higher basal
      leucine rate of appearance per kg FFM (BTHS: 271.4 +/- 69.3 vs. CONTROL: 193.1 +/
      28.7 MUmol/kgFFM/hr, p = 0.07) compared to controls. Higher basal leucine rate
      of appearance per kg FFM (i.e. whole-body proteolytic rate) tended to be
      associated with lower left ventricular systolic strain (r = -0.57, p = 0.09).
      CONCLUSION: Whole-body fatty acid, glucose and amino acid metabolism kinetics
      when expressed per unit of body composition are altered and appear to be related
      to cardioskeletal myopathy in humans with BTHS. Further studies examining
      myocardial substrate metabolism and whole-body substrate metabolism during
      increased energy demands (e.g., exercise) and their relationships to skeletal and
      cardiac function are recommended.

PMID- 22580964
TI  - In vitro labeling of endothelial progenitor cells isolated from peripheral blood
      with superparamagnetic iron oxide nanoparticles.
AB  - The transplantation of endothelial progenitor cells (EPCs) provides a novel
      method for the treatment of human tumors or vascular diseases. Magnetic resonance
      imaging (MRI) has proven to be effective in tracking transplanted stem cells by
      labeling the cells with superparamagnetic iron oxide (SPIO) nanoparticles. The
      SPIO has been used to label and track the EPCs; however, the effect of SPIO upon
      EPCs remains unclear on a cellular level. In the present study, EPCs were labeled
      with home-synthesized SPIO nanoparticles in vitro and the biological
      characteristics of the labeled EPCs were evaluated. The EPCs were isolated from
      the peripheral blood of New Zealand rabbits and cultured in fibronectin-coated
      culture flasks. The EPCs were labeled with home-synthesized SPIO nanoparticles at
      a final iron concentration of 20 ug/ml. Labeled EPCs were confirmed with
      transmission electron microscopy and Prussian blue staining. The quantity of
      iron/cell was detected by atomic absorption spectrometry. The membranous antigens
      of EPCs were detected by cytofluorimetric analysis. Cell viability and
      proliferative capability between the labeled and unlabeled EPCs were compared.
      The rabbit EPCs were effectively labeled and the labeling efficiency was
      approximately 95%. The SPIO nanoparticles were localized in the endosomal
      vesicles of the EPCs, which were confirmed by transmission electron microscopy.
      No significant differences were found in cell viability and proliferative
      capability between labeled and unlabeled EPCs (P>0.05). In conclusion, rabbit
      peripheral blood EPCs were effectively labeled by home-synthesized SPIO
      nanoparticles, without influencing their main biological characteristics.

PMID- 22580965
TI  - Effects of an evaporative cooling system on plasma cortisol, IGF-I, and milk
      production in dairy cows in a tropical environment.
AB  - Access to an evaporative cooling system can increase production in dairy cows
      because of improved thermal comfort. This study aimed to evaluate the impact of
      ambient temperature on thermoregulation, plasma cortisol, insulin-like growth
      factor 1 (IGF-I), and productive status, and to determine the efficiency of an
      evaporative cooling system on physiological responses under different weather
      patterns. A total of 28 Holstein cows were divided into two groups, one with and
      the other without access to a cooling system with fans and mist in the free
      stall. The parameters were analyzed during morning (0700 hours) and afternoon
      milking (1430 hours) under five different weather patterns throughout the year
      (fall, winter, spring, dry summer, and rainy summer). Rectal temperature (RT),
      body surface temperature (BS), base of tail temperature (TT), and respiratory
      frequency (RF) were lower in the morning (P < 0.01). The cooling system did not
      affect RT, and both the groups had values below 38.56 over the year (P = 0.11).
      Cortisol and IGF-I may have been influenced by the seasons, in opposite ways.
      Cortisol concentrations were higher in winter (P < 0.05) and IGF-I was higher
      during spring-summer (P < 0.05). The air temperature and the temperature humidity
      index showed positive moderate correlations to RT, BS, TT, and RF (P < 0.001).
      The ambient temperature was found to have a positive correlation with the
      physiological variables, independent of the cooling system, but cooled animals
      exhibited higher milk production during spring and summer (P < 0.01).

PMID- 22580966
TI  - Placebo by proxy: the effect of parents' beliefs on therapy for children's temper
      tantrums.
AB  - A placebo by proxy effect occurs when a patient's response to therapy, assessed
      either objectively or subjectively, is affected by the behavior of other people
      who know that the patient is undergoing therapy. We recruited 58 children aged 2
      5 years who reported frequent tantrums and examined the effect of a
      pharmacologically inert substance (flower essence) that is purported by the
      manufacturers to reduce temper tantrums. Tantrum frequency, tantrum severity, and
      parental mood were measured on 5 occasions over 8 days before treatment and on a
      further 5 occasions over 10 days after the start of treatment. Compared to the
      period before treatment, there was a continuing reduction in tantrum frequency (p
      = .002) and severity (p = .003) over the 8 days of placebo treatment. There were
      significant day-to-day correlations between parents' mood and tantrum frequency
      (r = .23) and severity (r = .19). Children's response to treatment for tantrums
      is associated with the beliefs and mood of the adult carer. We cannot say whether
      tantrum reduction was due to objective changes in child behavior, changes in
      parental perception, or both, but both are clinically important changes. 

PMID- 22580967
TI  - Inheritance of resistance to Ug99 stem rust in wheat cultivar Norin 40 and
      genetic mapping of Sr42.
AB  - Stem rust, caused by Puccinia graminis f. sp. tritici, is a devastating disease
      of wheat. The emergence of race TTKSK (Ug99) and new variants in Africa threatens
      wheat production worldwide. The best method of controlling stem rust is to deploy
      effective resistance genes in wheat cultivars. Few stem rust resistance (Sr)
      genes derived from the primary gene pool of wheat confer resistance to TTKSK.
      Norin 40, which carries Sr42, is resistant to TTKSK and variants TTKST and TTTSK.
      The goal of this study was to elucidate the inheritance of resistance to Ug99 in
      Norin 40 and map the Sr gene(s). A doubled haploid (DH) population of LMPG
      6/Norin 40 was evaluated for resistance to the race TTKST. Segregation of 248 DH
      lines fitted a 1:1 ratio (chi (2) 1:1= 0.58, p = 0.45), indicating a single gene
      in Norin 40 conditioned resistance to Ug99. This was confirmed by an independent
      F(2:3) population also derived from the cross LMPG-6/Norin 40 where a 1:2:1 ratio
      (chi (2)1:2:1 = 0.69, p = 0.71) was observed following the inoculation with race
      TTKSK. Mapping with DNA markers located this gene to chromosome 6DS, the known
      location of Sr42. PCR marker FSD_RSA co-segregated with Sr42, and simple sequence
      repeat (SSR) marker BARC183 was closely linked (0.5 cM) to Sr42. A previous study
      found close linkage between FSD_RSA and SrCad, a temporarily designated gene that
      also confers resistance to Ug99, thus Sr42 may be the same gene or allelic.
      Marker FSD_RSA is suitable for marker-assisted selection (MAS) in wheat breeding
      programs to improve stem rust resistance, including Ug99.

PMID- 22580968
TI  - Genetic components and major QTL confer resistance to bean pyralid (Lamprosema
      indicata Fabricius) under multiple environments in four RIL populations of
      soybean.
AB  - Bean pyralid (BP; Lamprosema indicata Fabricius) is one of the major leaf-feeding
      insects that affect soybean crops in central and southern China. Four recombinant
      inbred line populations (KY, WT, XG and SX) were tested during 2004-2006 in
      Nanjing, China, to identify quantitative trait loci (QTL) for resistance to BP on
      the basis of data for rolled leaflet percentage under field infestation
      conditions. The mapping was performed using QTL Network V2.0 and checked with
      Windows QTL Cartographer V2.5 and IciMapping V2.2. The results showed that 81-92
      % of the phenotypic variation was accounted for by additive QTL (27-43 %),
      epistatic QTL pairs (5-13 %), and collective unmapped minor QTL (38-58 %). In
      total, 17 QTL were detected on 11 linkage groups, of which two had additive
      effects, six had both additive and epistatic effects, and nine had only epistatic
      effects. Eight epistatic QTL pairs were observed, of which three pairs involved
      two QTL with additive effects, one involved one QTL with additive effect, and
      four involved no QTL with additive effects. Different genetic structures for BP
      resistance were found among the populations. Eight QTL (five additive and three
      epistatic pairs) were detected in KY, ten QTL (four additive and five epistatic
      pairs) were detected in WT, and only one additive QTL was detected in both the XG
      and the SX populations. BP12-1 and BP1-1 are major QTL, with the former
      accounting for 15, 31, and 50 % of the total genetic variation (including
      epistasis) in KY, WT, and XG, respectively, and the latter accounting for 13 and
      32 % of the total genetic variation in KY and SX, respectively. The additive *
      year and epistasis * year interaction effects were negligible, indicating that
      the QTL were stable over the years. Because 41-68 % of the total genetic
      variation could not be accounted for by these QTL, the use of both identified QTL
      and unmapped minor QTL in breeding for BP resistance should be considered.

PMID- 22580970
TI  - The structure of MgO-SiO2 glasses at elevated pressure.
AB  - The magnesium silicate system is an important geophysical analogue and neutron
      diffraction data from glasses formed in this system may also provide an initial
      framework for understanding the structure-dependent properties of related liquids
      that are important during planetary formation. Neutron diffraction data collected
      in situ for a single composition (38 mol% SiO(2)) magnesium silicate glass sample
      shows local changes in structure as pressure is increased from ambient conditions
      to 8.6 GPa at ambient temperature. A method for obtaining the fully corrected,
      total structure factor, S(Q), has been developed that allows accurate structural
      characterization as this weakly scattering glass sample is compressed. The
      measured S(Q) data indicate changes in chemical ordering with pressure and the
      real-space transforms show an increase in Mg-O coordination number and a
      distortion of the local environment around magnesium ions. We have used reverse
      Monte Carlo methods to compare the high pressure and ambient pressure structures
      and also compare the high pressure form with a more silica-poor glass
      (Mg(2)SiO(4)) that represents the approach to a more dense, void-free and
      topologically ordered structure. The Mg-O coordination number increases with
      pressure and we also find that the degree of continuous connectivity of Si-O
      bonds increases via a collapse of interstices.

PMID- 22580969
TI  - Evidence of selection on fatty acid biosynthetic genes during the evolution of
      cultivated sunflower.
AB  - The identification of genes underlying the phenotypic transitions that took place
      during crop evolution, as well as the genomic extent of resultant selective
      sweeps, is of great interest to both evolutionary biologists and applied plant
      scientists. In this study, we report the results of a molecular evolutionary
      analysis of 11 genes that underlie fatty acid biosynthesis and metabolism in wild
      and cultivated sunflower (Helianthus annuus). Seven of these 11 genes showed
      evidence of selection at the nucleotide level, with 1 (FAD7) having experienced
      selection prior to domestication, 2 (FAD2-3 and FAD3) having experienced
      selection during domestication, and 4 (FAB1, FAD2-1, FAD6, and FATB) having
      experienced selection during the subsequent period of improvement. Sequencing of
      a subset of these genes from an extended panel of sunflower cultivars revealed
      little additional variation, and an analysis of the genomic region surrounding
      one of these genes (FAD2-1) revealed the occurrence of an extensive selective
      sweep affecting a region spanning at least ca. 100 kb. Given that previous
      population genetic analyses have revealed a relatively rapid decay of linkage
      disequilibrium in sunflower, this finding indicates the occurrence of strong
      selection and a rapid sweep.

PMID- 22580971
TI  - Bilateral dissemination of malignant pleural mesothelioma via iatrogenic buffalo
      chest: a rare route of disease progression.
AB  - Buffalo chest refers to the pleuro-pleural communication that results in a single
      pleural cavity. Iatrogenic buffalo chest can occur following heart or heart-lung
      transplantation and other major thoracic surgeries. We present the case of
      malignant pleural mesothelioma in which iatrogenic buffalo chest after extended
      thymectomy caused bilateral pneumothoraces and contralateral dissemination of the
      disease. The free communication between bilateral pleural cavities had
      facilitated the rapid progression of tumor and the consequent bilateral malignant
      pleural effusions had made the management of disease much more difficult, leading
      to the early fatal outcome. To our knowledge, this is the first case of buffalo
      chest that was associated with bilateral malignant pleural effusions.

PMID- 22580972
TI  - Five-year tumor-free survival after aggressive trimodality therapy for T3N0M1b
      non-small cell lung cancer with synchronous solitary brain metastasis.
AB  - Several recent studies have demonstrated that some patients might benefit from
      aggressive therapy for thoracic stage I lung cancer and synchronous solitary
      brain metastasis. However, the indication for the patients with advanced T-stage
      is still unclear. We herein present a patient with synchronous solitary brain
      metastasis from non-small cell lung cancer who survived without recurrence for 5
      years following surgery after chemotherapy, even though the primary tumor was
      T3N0 thoracic stage II. Aggressive treatment for both the primary site and brain
      metastasis may therefore be an effective treatment for locally advanced non-small
      cell lung cancer patients with synchronous solitary brain metastasis.

PMID- 22580973
TI  - Is the mid-term outcome of free right internal thoracic artery with a proximal
      anastomosis modification inferior to in situ right internal thoracic artery?
AB  - BACKGROUND: We investigated the mid-term results of free right internal thoracic
      artery (RITA) grafts used in an aorto-coronary fashion with a modified proximal
      anastomosis. METHODS: The subjects were 214 patients who underwent coronary
      artery bypass grafting with anastomosis to the left circumflex arteries using the
      RITA as a free graft (Group A: 158 patients) or an in situ graft (Group B: 56
      patients). In Group A, the proximal end of the free RITA was anastomosed onto the
      ascending aorta interposing free graft tissue or to part of its own tissue as a
      cuff. RESULTS: The number of RITA anastomoses was 1.38 +/- 0.50 in Group A and
      1.04 +/- 0.19 in Group B (P < 0.001). The relationship between perioperative
      variables and mid-term outcomes was assessed using Cox proportional hazard
      models. Survival was not associated with the way the RITA graft was performed
      (Hazard Ratio 5.26, 95 % CI 0.52-53.1, P = 0.159), however, the number of cardiac
      events was decreased in Group A (Hazard Ratio 2.55, 95 % CI 1.03-6.33, P =
      0.043). The graft patency was evaluated in 187 of 214 patients, and at 1, 3 and 5
      years was 97.0, 97.0 and 97.0 % in Group A, and 97.9, 92.5 and 80.5 % in Group B
      (P = 0.378), respectively. CONCLUSION: By modifying the proximal anastomosis of
      the free RITA, cardiac events may be decreased, while survival and graft patency
      comparable with in situ RITA can be obtained, and a significantly larger number
      of targets can be revascularized.

PMID- 22580974
TI  - Strategies to reduce dietary sodium intake.
AB  - OPINION STATEMENT: Excess sodium intake has an important, if not predominant,
      role in the pathogenesis of elevated blood pressure, one of the most important
      modifiable determinants of cardiovascular disease (CVD). In the United States,
      almost 80 % of sodium in the diet comes from packaged and restaurant foods. Given
      the current food environment, educational efforts such as clinician counseling
      are useful, but a comprehensive public health approach is necessary to achieve
      meaningful reductions in sodium intake. A successful approach includes several
      key strategies, which together will both promote positive decisions by
      individuals and change the context in which they make those decisions. The
      strategies include 1) public education, 2) individual dietary counseling, 3) food
      labeling, 4) coordinated and voluntary industry sodium reduction, 5) government
      and private sector food procurement policies, and 6) FDA regulations, as
      recommended by the Institute of Medicine, to modify sodium's generally regarded
      as safe (GRAS) status. Population-wide reduction in sodium intake has the
      potential to substantially reduce the public burden of preventable CVD and reduce
      health care costs.

PMID- 22580975
TI  - Editorial: pediatric solid tumors.

PMID- 22580976
TI  - An integrated approach to change the outcome part I: neuromuscular screening
      methods to identify high ACL injury risk athletes.
AB  - An important step for treatment of a particular injury etiology is the
      appropriate application of a treatment targeted to the population at risk. An
      anterior cruciate ligament (ACL) injury risk algorithm has been defined that
      employs field-based techniques in lieu of laboratory-based motion analysis
      systems to identify athletes with high ACL injury risk landing strategies. The
      resultant field-based assessment techniques, in combination with the developed
      prediction algorithm, allow for low-cost identification of athletes who may be at
      increased risk of sustaining ACL injury. The combined simplicity and accuracy of
      the field-based tool facilitate its use to identify specific factors that may
      increase risk of injury in female athletes. The purpose of this report is to
      demonstrate novel algorithmic techniques to accurately capture and analyze
      measures of knee valgus motion, knee flexion range of motion, body mass, tibia
      length and quadriceps to hamstrings ratio with video analysis software typically
      used by coaches, strength and conditioning specialists, and athletic trainers.
      The field-based measurements and software analyses were used in a prediction
      algorithm to identify those at potential risk of noncontact ACL injury that may
      directly benefit from neuromuscular training.

PMID- 22580977
TI  - An acute bout of self-myofascial release increases range of motion without a
      subsequent decrease in muscle activation or force.
AB  - Foam rolling is thought to improve muscular function, performance, overuse, and
      joint range of motion (ROM); however, there is no empirical evidence
      demonstrating this. Thus, the objective of the study was to determine the effect
      of self-myofascial release (SMR) via foam roller application on knee extensor
      force and activation and knee joint ROM. Eleven healthy male (height 178.9 +/-
      3.5 cm, mass 86.3 +/- 7.4 kg, age 22.3 +/- 3.8 years) subjects who were
      physically active participated. Subjects' quadriceps maximum voluntary
      contraction force, evoked force and activation, and knee joint ROM were measured
      before, 2 minutes, and 10 minutes after 2 conditions: (a) 2, 1-minute trials of
      SMR of the quadriceps via a foam roller and (b) no SMR (Control). A 2-way
      analysis of variance (condition * time) with repeated measures was performed on
      all dependent variables recorded in the precondition and postcondition tests.
      There were no significant differences between conditions for any of the
      neuromuscular dependent variables. However, after foam rolling, subjects' ROM
      significantly (p < 0.001) increased by 10 degrees  and 8 degrees  at 2 and 10
      minutes, respectively. There was a significant (p < 0.01) negative correlation
      between subjects' force and ROM before foam rolling, which no longer existed
      after foam rolling. In conclusion, an acute bout of SMR of the quadriceps was an
      effective treatment to acutely enhance knee joint ROM without a concomitant
      deficit in muscle performance.

PMID- 22580978
TI  - Meta-analysis of postactivation potentiation and power: effects of conditioning
      activity, volume, gender, rest periods, and training status.
AB  - There is no clear agreement regarding the ideal combination of factors needed to
      optimize postactivation potentiation (PAP) after a conditioning activity.
      Therefore, a meta-analysis was conducted to evaluate the effects of training
      status, volume, rest period length, conditioning activity, and gender on power
      augmentation due to PAP. A total of 141 effect sizes (ESs) for muscular power
      were obtained from a total of 32 primary studies, which met our criteria of
      investigating the effects of a heavy preconditioning activity on power in
      randomized human trials. The mean overall ES for muscle power was 0.38 after a
      conditioning activity (p < 0.05). Significant differences were found between
      moderate intensity (60-84%) 1.06 and heavy intensity (>85%) 0.31 (p < 0.05).
      There were overall significant differences found between single sets 0.24 and
      multiple sets 0.66 (p < 0.05). Rest periods of 7-10 minutes (0.7) after a
      conditioning activity resulted in greater ES than 3-7 minutes (0.54), which was
      greater than rest periods of >10 minutes (0.02) (p < 0.05). Significant
      differences were found between untrained 0.14 and athletes 0.81 and between
      trained 0.29 and athletes. The primary findings of this study were that a
      conditioning activity augmented power output, and these effects increased with
      training experience, but did not differ significantly between genders. Moreover,
      potentiation was optimal after multiple (vs. single) sets, performed at moderate
      intensities, and using moderate rest periods lengths (7-10 minutes).

PMID- 22580979
TI  - Variants of the ankyrin repeat domain 6 gene (ANKRD6) and muscle and physical
      activity phenotypes among European-derived American adults.
AB  - Ankyrin repeat domain 6 (ANKRD6) is a ubiquitous protein that associates with
      early development in mammals and is highly expressed in the brain, spinal cord,
      and heart of humans. We examined the role of 8 ANKRD6 single-nucleotide
      polymorphisms (SNPs) on muscle performance and habitual physical activity (PA).
      Single-nucleotide polymorphisms were 545 T>A (rs9362667), 485 M>L (rs61736690),
      233 T>M (rs2273238), 128 I>L (rs3748085), 631 P>L (rs61739327), 122 Q>E
      (rs16881983), 197805 G>A (rs9344950), and 710 L>X (NOVEL). This study consisted
      of 922 healthy, untrained, European-derived American men (n = 376, 23.6 +/- 0.3
      years, 25.0 +/- 0.2 kg.m(-2)) and women (n = 546, 23.2 +/- 0.2 years, 24.0 +/-
      0.2 kg.m(-2)). Muscle strength (maximum voluntary contraction [MVC] and 1
      repetition maximum [1RM]) and size (cross-sectional area [CSA]) were assessed
      before and after 12 weeks of unilateral resistance training (RT). A subsample (n
      = 536, 23.4 +/- 0.2 years, 24.6 +/- 0.2 kg.m(-2)) completed the Paffenbarger
      Physical Activity Questionnaire. Associations among ANKRD6 genotypes and muscle
      phenotypes were tested with repeated measure analysis of covariance (ANCOVA) and
      PA phenotypes with multivariate ANCOVA, with age and body mass index as
      covariates. ANKRD6 122 Q>E was associated with increased baseline biceps CSA.
      ANKRD6 545 A>T and ANKRD6 710 L>X were associated with increased 1RM and MVC in
      response to RT, respectively. ANKRD6 631 P>L was associated with increased biceps
      CSA response to RT and time spent in moderate-intensity PA among the total sample
      and women. ANKRD6 genetic variants were associated with the muscle size and
      strength response to RT and habitual PA levels. Further research is needed to
      validate our results and explore mechanisms for the associations we observed.

PMID- 22580980
TI  - An integrated approach to change the outcome part II: targeted neuromuscular
      training techniques to reduce identified ACL injury risk factors.
AB  - Prior reports indicate that female athletes who demonstrate high knee abduction
      moments (KAMs) during landing are more responsive to neuromuscular training
      designed to reduce KAM. Identification of female athletes who demonstrate high
      KAM, which accurately identifies those at risk for noncontact anterior cruciate
      ligament (ACL) injury, may be ideal for targeted neuromuscular training. Specific
      neuromuscular training targeted to the underlying biomechanical components that
      increase KAM may provide the most efficient and effective training strategy to
      reduce noncontact ACL injury risk. The purpose of the current commentary is to
      provide an integrative approach to identify and target mechanistic underpinnings
      to increased ACL injury in female athletes. Specific neuromuscular training
      techniques will be presented that address individual algorithm components related
      to high knee load landing patterns. If these integrated techniques are employed
      on a widespread basis, prevention strategies for noncontact ACL injury among
      young female athletes may prove both more effective and efficient.

PMID- 22580981
TI  - Kettlebell swing training improves maximal and explosive strength.
AB  - The aim of this study was to establish the effect that kettlebell swing (KB)
      training had on measures of maximum (half squat-HS-1 repetition maximum [1RM])
      and explosive (vertical jump height-VJH) strength. To put these effects into
      context, they were compared with the effects of jump squat power training (JS
      known to improve 1RM and VJH). Twenty-one healthy men (age = 18-27 years, body
      mass = 72.58 +/- 12.87 kg) who could perform a proficient HS were tested for
      their HS 1RM and VJH pre- and post-training. Subjects were randomly assigned to
      either a KB or JS training group after HS 1RM testing and trained twice a week.
      The KB group performed 12-minute bouts of KB exercise (12 rounds of 30-second
      exercise, 30-second rest with 12 kg if <70 kg or 16 kg if >70 kg). The JS group
      performed at least 4 sets of 3 JS with the load that maximized peak power
      Training volume was altered to accommodate different training loads and ranged
      from 4 sets of 3 with the heaviest load (60% 1RM) to 8 sets of 6 with the
      lightest load (0% 1RM). Maximum strength improved by 9.8% (HS 1RM: 165-181% body
      mass, p < 0.001) after the training intervention, and post hoc analysis revealed
      that there was no significant difference between the effect of KB and JS training
      (p = 0.56). Explosive strength improved by 19.8% (VJH: 20.6-24.3 cm) after the
      training intervention, and post hoc analysis revealed that the type of training
      did not significantly affect this either (p = 0.38). The results of this study
      clearly demonstrate that 6 weeks of biweekly KB training provides a stimulus that
      is sufficient to increase both maximum and explosive strength offering a useful
      alternative to strength and conditioning professionals seeking variety for their
      athletes.

PMID- 22580982
TI  - Gender-specific influences of balance, speed, and power on agility performance.
AB  - The quick change of direction (i.e., agility) is an important athletic ability in
      numerous sports. Because of the diverse and therefore hardly predictable
      manifestations of agility in sports, studies noted that the improvement in speed,
      power, and balance should result in an improvement of agility. However, there is
      evident lack of data regarding the influence of potential predictors on different
      agility manifestations. The aim of this study was to determine the gender
      specific influence of speed, power, and balance on different agility tests. A
      total of 32 college-aged male athletes and 31 college-aged female athletes (age
      20.02 +/- 1.89 years) participated in this study. The subjects were mostly
      involved in team sports (soccer, team handball, basketball, and volleyball; 80%
      of men, and 75% of women), martial arts, gymnastics, and dance. Anthropometric
      variables consisted of body height, body weight, and the body mass index. Five
      agility tests were used: a t-test (T-TEST), zig-zag test, 20-yard shuttle test,
      agility test with a 180-degree turn, and forward-backward running agility test
      (FWDBWD). Other tests included 1 jumping ability power test (squat jump, SQJ), 2
      balance tests to determine the overall stability index and an overall limit of
      stability score (both measured by Biodex Balance System), and 2 running speed
      tests using a straight sprint for 10 and 20 m (S10 and S20, respectively). A
      reliability analysis showed that all the agility tests were reliable. Multiple
      regression and correlation analysis found speed and power (among women), and
      balance (among men), as most significant predictors of agility. The highest
      Pearson's correlation in both genders is found between the results of the FWDBWD
      and S10M tests (0.77 and 0.81 for men and women, respectively; p < 0.05). Power,
      measured using the SQJ, is significantly (p < 0.05) related to FWDBWD and T-TEST
      results but only for women (-0.44; -0.41). The balance measures were
      significantly related to the agility performance for men but not for women. In
      addition to demonstrating a known relationship between speed and agility in both
      genders, and a small but statistically significant relationship between power and
      agility in women, these results indicate that balance should be considered as a
      potential predictor of agility in trained adult men.

PMID- 22580983
TI  - Integration core exercises elicit greater muscle activation than isolation
      exercises.
AB  - The American College of Sports Medicine and the United States Department of
      Health and Human Services advocate core training as a means to improve stability,
      reduce injury, and maintain mobility. There are countless exercises that target
      the primary core trunk muscles (abdominal and lumbar) with the aim of providing
      these benefits. However, it is unknown as to which exercises elicit the greatest
      activation thereby maximizing functional gains and peak performance. Thus, our
      purpose was to determine whether integration core exercises that require
      activation of the distal trunk muscles (deltoid and gluteal) elicit greater
      activation of primary trunk muscles in comparison with isolation core exercises
      that only require activation of the proximal trunk muscles. Twenty participants,
      10 men and 10 women, completed 16 randomly assigned exercises (e.g., crunch,
      upper body extension, and hover variations). We measured muscle activity with
      surface electromyography of the anterior deltoid, rectus abdominus, external
      abdominal oblique, lumbar erector spinae, thoracic erector spinae, and gluteus
      maximus. Our results indicate that the activation of the abdominal and lumbar
      muscles was the greatest during the exercises that required deltoid and gluteal
      recruitment. In conclusion, when completing the core strength guidelines, an
      integrated routine that incorporates the activation of distal trunk musculature
      would be optimal in terms of maximizing strength, improving endurance, enhancing
      stability, reducing injury, and maintaining mobility.

PMID- 22580984
TI  - Loss of 15-hydroxyprostaglandin dehydrogenase indicates a tumor suppressor role
      in pituitary adenomas.
AB  - 15-hydroxyprostaglandin dehydrogenase (15-PGDH) may function as a tumor
      suppressor that antagonizes the action of the cyclooxygenase-2 (COX-2) oncogene
      in several types of tumors. However, it is unknown if it has a role in the
      pituitary. Recently, our group found that 15-PGDH expression was low in prolactin
      (PRL) secreting adenomas (prolactinomas) and growth hormone (GH) secreting
      adenomas (GHomas) using fiber-optic BeadArray technology. In this study, we
      examined the relative expression of 15-PGDH and COX-2 mRNA in clinical specimens
      and examined the effects of 15-PGDH on GH3 rat pituitary tumor cell
      proliferation, apoptosis and hormone secretion. 15-PGDH expression was lower and
      COX-2 expression was higher in prolactinomas and GHomas compared with normal
      controls. Overexpressed 15-PGDH inhibited tumor cell proliferation and induced
      apoptosis. It had a significant suppressive effect on mRNA levels and on the
      secretion of PRL and GH in GH3 cells. The inhibition of cell proliferation was
      accompanied by the decreased expression of cox-2, matrix metalloproteinase-9 (MMP
      9) and B cell leukemia/lymphoma-2 (Bcl-2). These data are suggestive of a
      previously unrecognized pathway in pituitary tumorigenesis, and this novel
      observation may shed light on therapeutic strategies for pituitary tumors.

PMID- 22580985
TI  - Radiographic findings of the medial humeral epicondyle in 200 canine elbow
      joints.
AB  - OBJECTIVES: To determine the frequency and radiographic aspect of medial humeral
      epicondylar lesions as a primary or concomitant finding and to evaluate the
      association with osteoarthritis. METHODS: Medical records of dogs diagnosed with
      elbow lameness were reviewed. Inclusion criteria for this study were a complete
      clinical examination, a complete set of digital radiographs and a final diagnosis
      made by computed tomography or magnetic resonance imaging and arthroscopy.
      Changes of the medial humeral epicondyle were recorded and correlated with the
      radiographic osteoarthritis and final diagnosis. RESULTS: Eighty of the 200
      elbows showed changes of the medial humeral epicondyle. In 12 of these 80 elbows,
      changes of the medial epicondyle were the only findings within the joint, and
      these elbows were diagnosed with primary flexor enthesopathy. In the remaining 68
      elbows, other concomitant elbow pathologies were found. In those cases of
      concomitant epicondylar changes, high grades of osteoarthritis were recorded,
      while most elbows with primary flexor enthesopathy showed a low grade of
      osteoarthritis. CLINICAL SIGNIFICANCE: Changes of the medial humeral epicondyle
      are often considered clinically unimportant and are regarded as an expression of
      osteoarthritis. This study showed the relatively frequent presence of epicondylar
      changes of which the majority were considered concomitant to a primary elbow
      problem. If changes of the medial humeral epicondyle are the only pathologic
      finding (primary flexor enthesopathy) they should be considered as the cause of
      lameness and not as a sign of osteoarthritis.

PMID- 22580986
TI  - Development and characterization of a preclinical ovarian carcinoma model to
      investigate the mechanism of acquired resistance to trastuzumab.
AB  - Trastuzumab (Herceptin(r)) is a humanized monoclonal antibody designed to bind
      and inhibit the function of the human epidermal growth factor receptor 2
      (HER2)/erbB2 receptor. Trastuzumab has demonstrated clinical activity in several
      types of HER2-overexpressing epithelial tumors, such as breast and metastatic
      gastric or gastroesophageal junction cancer. Relapse and therapeutic resistance,
      however, still occur in a subset of patients treated with regimens including
      trastuzumab, despite significant improvements in response rates, survival and
      quality of life. To investigate the potential mechanisms of acquired therapeutic
      resistance to trastuzumab, we developed a preclinical model of human ovarian
      cancer cells, SKOV-3 Herceptin-resistant (HR), and examined the corresponding
      changes in gene expression profiles. SKOV-3 HR cells were developed by in vivo
      serial passaging of parental trastuzumab-sensitive SKOV-3 cells. Following four
      rounds of serial transplantation of 'break-through' xenograft tumors under
      trastuzumab treatment, significant and reproducible differences in the effects of
      trastuzumab treatment between SKOV-3 HR and SKOV-3 cells in vivo and in vitro
      were revealed. SKOV-3 HR cells retained HER2 protein expression but were
      unaffected by the antiproliferative effects of trastuzumab. The trastuzumab
      binding affinity for SKOV-3 HR cells was diminished, despite these cells having
      more binding sites for trastuzumab. Microarray expression profiling (MEP) was
      performed to determine the genes involved in the resistance mechanism. Functional
      analysis revealed the differential expression of genes potentially involved in
      angiogenesis, metastasis, differentiation and proliferation, such as mucin1
      (MUC1). Immunohistochemical staining of SKOV-3 HR cells demonstrated a marked
      overexpression of MUC1. Based on these data, we hypothesize that the
      overexpression of MUC1 may hinder trastuzumab binding to HER2 receptors,
      abrogating the antitumor effects of trastuzumab and thus could contribute to
      resistance to therapy. Moreover, the resultant MEP preclinical gene signature in
      this preclinical model system may provide the basis for further investigation of
      potential clinical mechanisms of resistance to trastuzumab.

PMID- 22580987
TI  - How useful are screening instruments for toddlers to predict outcome at age 4?
      General development, language skills, and symptom severity in children with a
      false positive screen for autism spectrum disorder.
AB  - Screening instruments for autism spectrum disorder (ASD) often generate many
      false positives. It is argued that these children may have other developmental
      difficulties and are also in need of thorough assessment and early intervention.
      The current study looked at the predictive validity of positive screens on the
      Checklist for Early Signs of Developmental Disorders (CESDD) and the Early
      Screening of Autistic Traits questionnaire (ESAT) at age 2 towards language,
      cognitive function, and symptom severity at age 4. Children who screened positive
      on the ESAT scored lower for both language and cognitive functioning at age 4
      compared with children who screened negative on the ESAT. Also, the more signs of
      ASD that were recognized on the CESDD or ESAT, the lower the scores for language
      and cognitive functioning at age 4. False positive screens could be
      differentiated from true positive screens on the CESDD only in symptom severity
      score on the Autism Diagnostic Observation Schedule (ADOS). It seems that early
      screeners for ASD also detect children with other developmental disorders and
      that diagnostic instruments such as the ADOS are warranted to differentiate
      between children with ASD and other developmental problems.

PMID- 22580988
TI  - Bilateral middle cerebral artery aneurysms: a comparative study of unilateral and
      bilateral approaches.
AB  - The best surgical method for the treatment of patients with bilateral middle
      cerebral artery (bMCA) aneurysms has not been fully determined yet. The main
      purpose of this study is to compare the surgical results of unilateral and
      bilateral approaches to bMCA aneurysms including mean operation time, mean
      hospital stay, and mean cost, in the experience of the same neurosurgical team.
      Between January 2001 and June 2010, 22 patients with bMCA aneurysms were
      surgically treated in our institution. In 12 cases (54.5 %), ipsilateral and
      contralateral MCA aneurysms were successfully clipped via unilateral approach. In
      the remaining 10 cases, bilateral approach was necessary because of some
      technical difficulties. Although the surgical results were almost the same, mean
      operation time and mean hospital stay were, respectively, 46 and 37 % shorter and
      mean cost per person was 23 % lower for the patients in the unilateral group. In
      addition, the severity of brain edema, total length of the contralateral (A1+M1)
      segment, and the configuration of contralateral aneurysm were found to be the
      determinant parameters affecting the feasibility of the unilateral approach. To
      our knowledge, this is the first study in the literature that compares the
      clinical outcomes of unilateral and bilateral approaches to bMCA aneurysms. The
      results of surgery for both approaches are almost the same. However, the
      unilateral approach has certain advantages compared to the bilateral approach.
      Therefore, the unilateral approach may be a good alternative in surgical
      management of patients with bMCA aneurysms in selected cases and the
      abovementioned parameters can help the neurosurgeon in patient selection.

PMID- 22580989
TI  - The Ex Vivo Eye Irritation Test (EVEIT) in evaluation of artificial tears: Purite
      preserved versus unpreserved eye drops.
AB  - OBJECTIVE: Preservatives in artificial tears cause controversy. New developments
      such as the Purite system have been introduced into the market, with the promise
      of little damage to the corneal surface. We wanted to give insight into the
      differences in the effect of preserved and unpreserved artifical tears on rabbit
      corneas cultured with the Ex Vivo Eye Irritation Test (EVEIT) system. MATERIALS:
      We compared the two artifical tears products Hylo Comod and Optive being dropped
      for 72 hours each hour one drop onto the corneal surface. METHODS: Each cornea
      was mechanically wounded with four epithelial defects on each cornea with a size
      of 3 to 4.5 mm(2). With n = 4 corneas in the Hylo-Comod and n = 4 corneas in the
      Optive group, we exposed the corneal surfaces to repeated doses of these
      artificial tears for 3 days. We observed healing of corneal erosions and surface
      epithelial integrity with sodium-fluoresceine staining under cobalt blue light
      illumination. RESULTS: We found nearly complete healing of epithelial defects
      with both artificial tears. The Hylo-Comod group healed significantly faster.
      After 72 hours, the vast majority of epithelial defects were closed. All corneas
      exposed to Purite showed superficial stippling, whereas the HyloComod group did
      not show any stippling of the cornea; this difference was significant.
      DISCUSSION: Epithelial healing and recovery in the EVEIT system is observed in
      both groups, confirming the concept of artificial tears as a supporting factor of
      corneal health and healing. The superficial stippling of the corneal epithelium
      was observed only in the Optive group. This effect is considered as a marker of
      dry eye syndrome, and should be prevented by the application of artificial tears.
      Preservative-free eye drops such as HyloComod improve healing, and prevent
      symptoms of dry eye syndrome in the EVEITsystem. Compared to EVEIT results of
      former experiments with benzalconium chloride-preserved eye drops, Optive
      promoted healing of corneal erosions.

PMID- 22580990
TI  - Outcome of iris fixation of subluxated intraocular lenses.
AB  - BACKGROUND: The aim of this study was to evaluate the efficacy of iris fixation
      of subluxated intraocular lenses (IOLs). METHODS: A retrospective study of 44
      consecutive cases of subluxated IOLs that underwent iris fixation of the IOL.
      Demographic information, data regarding surgery, and follow-up were retrieved
      from patient files. All eyes were operated on in a similar fashion by the same
      anterior segment surgeon (A.M.) utilizing the McCannel suture technique and/or
      the Siepser slipknot technique. The main outcome measures were visual acuity
      improvement, surgically induced astigmatism, and assessment of complications.
      RESULTS: Ten eyes had a documented complication during primary cataract
      extraction. Pseudoexfoliation was present in 11 eyes (25 %). History of ocular
      trauma and high myopia were present in six eyes (each). Excluding eyes with
      macular disease and very low visual acuity, visual acuity improved from 0.4 (+/-
      0.05) logMAR to 0.24 (+/- 0.05) logMAR (p = 0.047). Eyes with low pre-operative
      astigmatism did not worsen post-operatively (R square linear = 0.8, p < 0.01).
      Pupil ovalization was a major aesthetic complication (21 of 44 eyes). Major
      hemorrhagic complications were uncommon. One patient developed intermediate
      uveitis 1 year after IOL fixation. CONCLUSIONS: In this study of 44 eyes, iris
      fixation was proven to be a an effective method for treating subluxated IOLs.

PMID- 22580991
TI  - HbA(1c) variability and the development of microalbuminuria in type 2 diabetes:
      Tsukuba Kawai Diabetes Registry 2.
AB  - AIMS/HYPOTHESIS: The aim of this study was to examine the association between
      HbA(1c) variability and the development of microalbuminuria as defined by an
      albumin/creatinine ratio >= 3.4 mg/mmol (>= 30 mg/g) in at least two of three
      consecutive urine samples in Japanese patients with type 2 diabetes. METHODS:
      HbA(1c) level was measured in 812 serially registered normoalbuminuric adults
      aged 21-79 years with type 2 diabetes. After registration, a 1-year period to
      establish baseline values for mean HbA(1c) and HbA(1c) variability (measured as
      the intrapersonal SD of serially collected HbA(1c)) was decided upon. The
      association between HbA(1c) variability and the development of microalbuminuria
      was determined by Cox regression analysis after adjustment for other risk factors
      for microalbuminuria. RESULTS: Microalbuminuria occurred in 193 patients during
      the observation period of (mean +/- SD) 4.3 +/- 2.7 years. Even after adjustment
      for mean HbA(1c), HbA(1c) variability was a significant predictor of
      microalbuminuria independently of the mean HbA(1c); the HR for every 1% (95% CI)
      increase in mean HbA(1c) was 1.22 (1.06, 1.40) (p = 0.005), and that for HbA(1c)
      variability was 1.35 (1.05, 1.72) (p = 0.019). The effects of these two variables
      were quite similar when 1 SD was used; the HR for every 1 SD increase (95% CI) in
      HbA(1c) was 1.23 (1.07, 1.43) (p = 0.005), and that for HbA(1c) variability was
      1.20 (1.03, 1.39) (p = 0.019). CONCLUSIONS/INTERPRETATION: HbA(1c) variability
      affects the development of microalbuminuria independently of mean HbA(1c) in type
      2 diabetes. Further studies should be performed to evaluate the influence of
      HbA(1c) variability on other complications and in individuals of other
      ethnicities with type 2 diabetes.

PMID- 22580992
TI  - Angelika Bierhaus, 1962-2012.

PMID- 22580993
TI  - A thiol-mediated active membrane transport of selenium by erythroid anion
      exchanger 1 protein.
AB  - In this paper, we describe a thiol-mediated and energy-dependent membrane
      transport of selenium by erythroid anion exchanger 1 (AE1, also known as band 3
      protein). The AE1 is the most abundant integral protein of red cell membranes and
      plays a critical role in the carbon dioxide transport system in which carbon
      dioxide is carried as bicarbonate in the plasma. This protein mediates the
      membrane transport of selenium, an essential antioxidant micronutrient, from red
      cells to the plasma in a manner that is distinct from the already known anion
      exchange mechanism. In this pathway, selenium bound to the cysteine 93 of the
      hemoglobin beta chain (Hb-Cysbeta93) is transported by the relay mechanism to the
      Cys317 of the amino-terminal cytoplasmic domain of the AE1 on the basis of the
      intrinsic interaction between the two proteins and is subsequently exported to
      the plasma via the Cys843 of the membrane-spanning domain. The selenium export
      did not occur in plain isotonic buffer solutions and required thiols, such as
      albumin, in the outer medium. Such a membrane transport mechanism would also
      participate in the export pathways of the nitric oxide vasodilator activity and
      other thiol-reactive substances bound to the Hb-Cysbeta93 from red cells to the
      plasma and/or peripherals.

PMID- 22580994
TI  - Touchless gesture user interface for interactive image visualization in
      urological surgery.
AB  - PURPOSE: In the operating room (OR) a touchless interface is an ideal solution
      since it does not demand any physical contact and still can provide the necessary
      control features in a cleansed and sterilized environment. METHODS: Using open
      source software libraries and image processing techniques, we implemented a hand
      tracking and gesture recognition system based on the Kinect device that enables
      surgeon to successfully touchlessly navigate through the image in the
      intraoperative setting through a personal computer. We used the InVesalius
      software, which provides high-quality 3D reconstruction of medical images.
      RESULTS: Computed tomography data were intraoperatively fruitfully accessed
      through a simple and cheap solution in 4 tumor enucleations in 3 male patients in
      whom elective nephron-sparing surgeries were performed for small non-exophitic
      tumors. Mean tumor length was 2.7 cm (2.1, 2.7, 2.9 and 3.1 cm), and real-time
      ultrasound was not necessary for intraoperative identification in 3 of 4
      endorenal tumors. All pathological reports revealed renal cell carcinoma, Fuhrman
      grade I, and negative inked surgical margins. No intra- or postoperative
      complication was reported. CONCLUSIONS: For the first time in the literature, a
      touchless user interface solution applying the Kinect device showed to be very
      efficient and enabled a low-cost and accurate control of the software InVesalius
      intraoperative, just using hand gestures. It can be used with any mouse
      controlled software, opening an avenue for potential applications in many other
      areas, such as data visualization, augmented reality, accessibility, and
      robotics. The further validation and advancement of this technology are underway.

PMID- 22580995
TI  - Analysis of KLLN as a high-penetrance breast cancer predisposition gene.
AB  - KLLN is a p53 target gene with DNA binding function and represents a highly
      plausible candidate breast cancer predisposition gene. We screened for
      predisposing variants in 860 high-risk breast cancer families using high
      resolution melt analysis. A germline c.339_340delAG variant predicted to cause
      premature termination of the protein after 57 alternative amino acid residues was
      identified in 3/860 families who tested negative for BRCA1 and BRCA2 mutations
      and in 1/84 sporadic breast cancer cases. However, the variant was also detected
      in 2/182 families with known BRCA1 or BRCA2 mutations and in 2/464 non-cancer
      controls. Furthermore, loss of the mutant allele was detected in 2/2 breast
      tumors. Our data suggest that pathogenic mutations in KLLN are rare in breast
      cancer families and the c.339_340delAG variant does not represent a high
      penetrance breast cancer risk allele.

PMID- 22580996
TI  - Erythropoietin-driven signaling ameliorates the survival defect of DMT1-mutant
      erythroid progenitors and erythroblasts.
AB  - BACKGROUND: Hypochromic microcytic anemia associated with ineffective
      erythropoiesis caused by recessive mutations in divalent metal transporter 1
      (DMT1) can be improved with high-dose erythropoietin supplementation. The aim of
      this study was to characterize and compare erythropoiesis in samples from a DMT1
      mutant patient before and after treatment with erythropoietin, as well as in a
      mouse model with a DMT1 mutation, the mk/mk mice. DESIGN AND METHODS: Colony
      assays were used to compare the in vitro growth of pre-treatment and post
      treatment erythroid progenitors in a DMT1-mutant patient. To enable a comparison
      with human data, high doses of erythropoietin were administered to mk/mk mice.
      The apoptotic status of erythroblasts, the expression of anti-apoptotic proteins,
      and the key components of the bone marrow-hepcidin axis were evaluated. RESULTS:
      Erythropoietin therapy in vivo or the addition of a broad-spectrum caspase
      inhibitor in vitro significantly improved the growth of human DMT1-mutant
      erythroid progenitors. A decreased number of apoptotic erythroblasts was detected
      in the patient's bone marrow after erythropoietin treatment. In mk/mk mice,
      erythropoietin administration increased activation of signal transducer and
      activator of transcription 5 (STAT5) and reduced apoptosis in bone marrow and
      spleen erythroblasts. mk/mk mice propagated on the 129S6/SvEvTac background
      resembled DMT1-mutant patients in having increased plasma iron but differed by
      having functional iron deficiency after erythropoietin administration. Co
      regulation of hepcidin and growth differentiation factor 15 (GDF15) levels was
      observed in mk/mk mice but not in the patient. CONCLUSIONS: Erythropoietin
      inhibits apoptosis of DMT1-mutant erythroid progenitors and differentiating
      erythroblasts. Ineffective erythropoiesis associated with defective erythroid
      iron utilization due to DMT1 mutations has specific biological and clinical
      features.

PMID- 22580997
TI  - Development and validation of a predictive model for death in acquired severe
      ADAMTS13 deficiency-associated idiopathic thrombotic thrombocytopenic purpura:
      the French TMA Reference Center experience.
AB  - BACKGROUND: Acquired thrombotic thrombocytopenic purpura is still associated with
      a 10-20% death rate. It has still not been possible to clearly identify early
      prognostic factors of death. This study involved thrombotic thrombocytopenic
      purpura patients with acquired severe (<10% of normal activity) ADAMTS13
      deficiency and aimed to identify prognostic factors associated with 30-day death.
      DESIGN AND METHODS: The study involved a prospective cohort of patients and was
      carried out between October 2000 and August 2010. A validation cohort of patients
      was set up from September 2010 to August 2011. Altogether, 281 (analysis cohort)
      and 66 (validation cohort) consecutive adult thrombotic thrombocytopenic purpura
      patients with acquired severe ADAMTS13 deficiency were enrolled. The study
      evaluated 30-day mortality after treatment initiation according to
      characteristics at inclusion. RESULTS: Non-survivors (11%) were older (P=10(-6))
      and more frequently presented arterial hypertension (P=5.10(-4)) and ischemic
      heart disease (P=0.013). Prognosis was increasingly poor with age (P=0.004). On
      presentation, cerebral manifestations were more frequent in non-survivors
      (P=0.018) and serum creatinine level was higher (P=0.008). The most significant
      independent variables determining death were age, severe cerebral involvement and
      LDH level 10 N or over. A 3-level risk score for early death was defined and
      confirmed in the validation cohort using these variables, with higher values
      corresponding to increased risk of early death. CONCLUSIONS: A risk score for
      early death was defined in patients with thrombotic thrombocytopenic purpura and
      validated on an independent cohort. This score should help to stratify early
      treatment and identify patients with a worse prognosis.

PMID- 22580999
TI  - Excellent prognosis of late relapses of ETV6/RUNX1-positive childhood acute
      lymphoblastic leukemia: lessons from the FRALLE 93 protocol.
AB  - BACKGROUND: The prognosis of patients with relapses of ETV6/RUNX1-positive acute
      lymphoblastic leukemia remains to be evaluated, particularly with regards to the
      frequency of late relapses. We performed a long-term, follow-up retrospective
      study to address the outcome of patients with ETV6/RUNX1-positive leukemia
      relapses. DESIGN AND METHODS: Among the 713 children tested for ETV6/RUNX1
      enrolled into the FRALLE 93 protocol, 43 ETV6/RUNX1-positive patients relapsed
      (19.4%). Most were initially stratified in the low or intermediate risk groups.
      The median follow-up after relapse was 54.2 months. All but three received second
      line salvage therapy and 16 underwent allogeneic transplantation. RESULTS:
      ETV6/RUNX1 had a strong effect on overall survival after relapse (3-year
      survival= 64.7% for positive cases versus 46.5% for negative cases) (P=0.007).
      The 5-year cumulative incidence of relapse was 19.4% and testes were more
      frequently involved in ETV6/RUNX1-positive relapses (P=0.04). In 81.4% of cases
      the relapses were late, early combined or isolated extramedullary relapses. The 5
      year survival rate of patients with ETV6-RUNX1-positive acute lymphoblastic
      leukemia relapses reached 80.8% when the relapse occurred after 36 months (versus
      31.2% when the relapse occurred earlier). In univariate analysis, female gender
      was associated with a poor survival, whereas site of relapse, age at diagnosis,
      leukocytosis and consolidation strategy had no effect. In multivariate analysis,
      only the duration of first remission remained associated with outcome.
      CONCLUSIONS: We found an excellent outcome for patients with ETV6/RUNX1-positive
      leukemia relapses that occurred more than 36 months after diagnosis. The duration
      of first complete remission may, therefore, be a guide to define the treatment
      strategy for patients with relapsed ETV6/RUNX1- positive leukemia.

PMID- 22580998
TI  - DangER: protein ovERload. Targeting protein degradation to treat myeloma.
AB  - Myeloma is a malignancy of the antibody-producing plasma cells and, as such,
      these cells synthesize large quantities of unfolded or misfolded immunoglobulin.
      The build-up of excess protein triggers a number of downstream signal
      transduction cascades, including endoplasmic reticulum stress and autophagy. As a
      result, myeloma cells are uniquely reliant on these and other protein handling
      pathways for their survival. Strategies aimed at targeting this vulnerability
      have proved successful with the proteasome inhibitor, bortezomib, already
      licensed for clinical use. In addition to the proteasome, various other points
      within the protein handling pathways are also the subject of drug discovery
      projects, with some already progressing into clinical trials. These include
      compounds directed against heat shock proteins, the unfolded protein response and
      pathways both upstream and downstream of the proteasome. More recently, the role
      of autophagy has been recognized in myeloma. In this review, we discuss the
      various pathways used by myeloma cells for survival, with particular emphasis on
      the emerging role and conundrum of autophagy, as well as highlighting pre
      clinical research on novel inhibitors targeting protein handling pathways.

PMID- 22581000
TI  - Intensive chemotherapy with thiotepa, busulfan and cyclophosphamide and
      hematopoietic stem cell rescue in relapsed or refractory primary central nervous
      system lymphoma and intraocular lymphoma: a retrospective study of 79 cases.
AB  - BACKGROUND: Relapsing primary central nervous system lymphoma carries a poor
      prognosis when treated with conventional chemotherapy with a one-year overall
      survival of 25-40%. Encouraging results have been shown with intensive
      chemotherapy followed by autologous hematopoietic stem cell rescue. We report the
      results of a large multicenter retrospective analysis of intensive chemotherapy
      followed by hematopoietic stem cell rescue in immunocompetent adult patients with
      primary central nervous system lymphoma or intraocular lymphoma after the failure
      of high-dose methotrexate-based treatment. DESIGN AND METHODS: Patients were
      included if they received intensive chemotherapy with a combination of thiotepa,
      busulfan and cyclophosphamide. Seventy-nine patients (median age 52.4 years,
      range 23-67 years) were identified. All of the patients except 5 received a
      salvage treatment after the failure of high-dose methotrexate. After salvage
      treatment and just before intensive chemotherapy followed by hematopoietic stem
      cell rescue, 32 patients were in complete response, 26 patients were in partial
      response, 2 patients had stable disease and 19 patients had progressive disease.
      RESULTS: With a median follow up of 56 months, the 5-year overall survival
      probability was 51% in the whole population and 62% among patients who were
      chemosensitive to the salvage treatment. The 5-year event-free survival
      probability was 37.8% in the whole population and 43.7% in the chemosensitive
      subpopulation. Neurocognitive assessments in a subset of patients suggest no
      evidence of intensive chemotherapy-induced neurocognitive decline. CONCLUSIONS:
      Thiotepa, busulfan and cyclophosphamide-based intensive chemotherapy is an
      effective treatment for refractory and recurrent primary central nervous system
      lymphoma in chemosensitive patients up to 65 years of age. The role of intensive
      chemotherapy followed by hematopoietic stem cell rescue in chemorefractory
      patients needs to be more accurately defined.

PMID- 22581001
TI  - Time point-dependent concordance of flow cytometry and real-time quantitative
      polymerase chain reaction for minimal residual disease detection in childhood
      acute lymphoblastic leukemia.
AB  - BACKGROUND: Flow cytometric analysis of leukemia-associated immunophenotypes and
      polymerase chain reaction-based amplification of antigen-receptor genes
      rearrangements are reliable methods for monitoring minimal residual disease. The
      aim of this study was to compare the performances of these two methodologies in
      the detection of minimal residual disease in childhood acute lymphoblastic
      leukemia. DESIGN AND METHODS: Polymerase chain reaction and flow cytometry were
      simultaneously applied for prospective minimal residual disease measurements at
      days 15, 33 and 78 of induction therapy on 3565 samples from 1547 children with
      acute lymphoblastic leukemia enrolled into the AIEOP-BFM ALL 2000 trial. RESULTS:
      The overall concordance was 80%, but different results were observed according to
      the time point. Most discordances were found at day 33 (concordance rate 70%) in
      samples that had significantly lower minimal residual disease. However, the
      discordance was not due to different starting materials (total versus
      mononucleated cells), but rather to cell input number. At day 33, cases with
      minimal residual disease below or above the 0.01% cut-off by both methods showed
      a very good outcome (5-year event-free survival, 91.6%) or a poor one (5-year
      event-free survival, 50.9%), respectively, whereas discordant cases showed
      similar event-free survival rates (around 80%). CONCLUSIONS: Within the current
      BFM-based protocols, flow cytometry and polymerase chain reaction cannot simply
      substitute each other at single time points, and the concordance rates between
      their results depend largely on the time at which they are used. Our findings
      suggest a potential complementary role of the two technologies in optimizing risk
      stratification in future clinical trials.

PMID- 22581002
TI  - Clinical, immunophenotypic, cytogenetic, and molecular genetic features in 117
      adult patients with mixed-phenotype acute leukemia defined by WHO-2008
      classification.
AB  - Among 4,780 consecutive adult acute lymphoblastic/myeloblastic leukemia patients,
      we identified 117 (2.4%) patients with mixed-phenotype acute leukemia fulfilling
      WHO 2008 criteria; these were classified as: Blymphoid+ myeloid (n=64), T
      lymphoid+myeloid (n=38), B+T-lymphoid (n=14) and trilineage (n=1). Of 92 patients
      karyotyped, 59 were abnormal and were classified as: complex (22 of 92),
      t(9;22)(q34;q11) (14 of 92), monosomy 7 (7 of 92), polysomy 21 (7 of 92),
      t(v;11q23) (4 of 92), t(10;11)(p15;q21) (3 of 92), while STIL-TAL1 fusion was
      detected in one (T+My) patient. After investigating common acute leukemia-related
      mutations in 17 genes, 12 of 31 (39%) patients were found to have at least one
      mutation, classified with: IKZF1 deletion (4 of 31), and EZH2 (3 of 31), ASXL1 (3
      of 31), ETV6 (2 of 31), NOTCH1 (1 of 31), and TET2 (1 of 31) mutations. Array-CGH
      revealed genomic deletions of CDKN2A (4 of 12), IKZF1 (3 of 12), MEF2C (2 of 12),
      BTG1 (2 of 12), together with BCOR, EBF1, K-RAS, LEF1, MBNL1, PBX3, and RUNX1
      (one of 12 each). Our results indicate that mixed-phenotype acute leukemia is a
      complex entity with heterogeneous clinical, immunophenotypic, cytogenetic, and
      molecular genetic features.

PMID- 22581003
TI  - Molecular characterization of identical, novel MLL-EPS15 translocation and
      individual genomic copy number alterations in monozygotic infant twins with acute
      lymphoblastic leukemia.

PMID- 22581004
TI  - A novel deletion of beta-globin promoter causing high HbA2 in an Indian
      population.

PMID- 22581005
TI  - ETS1 encoding a transcription factor involved in B-cell differentiation is
      recurrently deleted and down-regulated in classical Hodgkin's lymphoma.

PMID- 22581006
TI  - Late stage erythroid precursor production is impaired in mice with chronic
      inflammation.
AB  - BACKGROUND: We and others have shown previously that over-expression of hepcidin
      antimicrobial peptide, independently of inflammation, induces several features of
      anemia of inflammation and chronic disease, including hypoferremia, sequestration
      of iron stores and iron-restricted erythropoiesis. Because the iron-restricted
      erythropoiesis evident in hepcidin transgenic mice differs from the normocytic,
      normochromic anemia most often observed in anemia of inflammation, we tested the
      hypothesis that chronic inflammation may contribute additional features to anemia
      of inflammation which continue to impair erythropoiesis following the acute phase
      of inflammation in which hepcidin is active. DESIGN AND METHODS: We compared
      erythropoiesis and iron handling in mice with turpentine-induced sterile
      abscesses with erythropoiesis and iron handling in hepcidin transgenic mice. We
      compared erythrocyte indices, expression of genes in the hepcidin regulatory
      pathway, tissue iron distribution, expression of heme and iron transport genes in
      splenic macrophages, the phenotype of erythroid maturation and chloromethyl
      dichlorodihydrofluorescein diacetate, acetyl ester fluorescence. RESULTS: Mice
      with sterile abscesses exhibited an intense, acute inflammatory phase followed by
      a mild to moderate chronic inflammatory phase. We found that erythrocytes in mice
      with sterile abscesses were normocytic and normochromic in contrast to those in
      hepcidin transgenic mice. We also observed that although hypoferremia resolved in
      the late phases of inflammation, erythropoiesis remained suppressed, with
      evidence of inefficient maturation of erythroid precursors in the bone marrow of
      mice with sterile abscesses. Finally, we observed increased oxidative stress in
      erythroid progenitors and circulating erythrocytes of mice with sterile abscesses
      which was not evident in hepcidin transgenic mice. CONCLUSIONS: Our results
      suggest that chronic inflammation inhibits late stages of erythroid production in
      the turpentine-induced sterile abscess model and induces features of impaired
      erythropoiesis which are distinct from those in hepcidin transgenic mice.

PMID- 22581007
TI  - Depletion of T regulatory cells through selection of CD127-positive cells results
      in a population enriched in memory T cells: implications for anti-tumor cell
      therapy.
AB  - BACKGROUND: Donor lymphocyte infusions can induce remissions in patients with
      relapse after allogeneic hematopoietic stem cell transplantation. Nevertheless,
      some grafted patients never display any signs of alloreactivity, either following
      allogeneic hematopoietic stem cell transplantation or after donor lymphocyte
      infusions. Consequently, they do not develop graft-versus-host disease and
      frequently do not respond to donor lymphocyte infusions. In a recently published
      clinical trial, we observed that elimination of CD4(+)CD25(+)Foxp3(+) natural
      regulatory T cells from the donor lymphocyte product could improve alloreactivity
      and the associated anti-tumor effect in a small proportion of patients with
      relapsed hematologic malignancies. Here, we aimed to improve the effect of donor
      lymphocyte infusion by modifying the procedure for depletion of T regulatory
      cells. DESIGN AND METHODS: We directly compared depletion of regulatory T cells
      from human peripheral blood mononuclear cells achieved by selection of CD127
      positive cells or by selection of CD25-negative cells. We tested the manipulated
      products (i) in vitro in mixed lymphocyte reactions and against pathogen-derived
      recall antigens and (ii) in vivo in experimental graft-versus-host disease.
      RESULTS: In vitro, we found that depletion of regulatory T cells through CD127
      positive selection improved both alloreactive and pathogen-specific immune
      responses. In vivo, we observed accelerated donor T-cell division and enhanced
      graft-versus-host disease due to efficient regulatory T-cell depletion
      accompanied by enrichment in memory T cells. CONCLUSIONS: Our results show that
      the strategy of CD127 positive selection is an efficient way of eliminating
      regulatory T cells from donor lymphocyte infusions and improves alloreactivity.
      This supports the investigation of CD127 positive selection in place of
      elimination of CD25-positive cells for clinical applications.

PMID- 22581009
TI  - Global transcriptional analysis of primitive thymocytes reveals accelerated
      dynamics of T cell specification in fetal stages.
AB  - T cell development constitutes a multistage process allowing the dissection of
      events resulting in cellular commitment and functional specification in a
      specialized microenvironment. This process is guided by the appropriate
      expression of regulatory genetic factors like transcriptional activators or
      repressors which are, in part, dependent on instructive signals of the
      microenvironment. To date, it remains unclear whether exactly the same genetic
      mechanism acts in adult compared to fetal T cell development. In order to
      directly compare T cell commitment during adult and fetal differentiation, we
      isolated subsequent stages of intrathymic subpopulations starting with early
      canonical T cell progenitors up to irreversibly committed T cell precursors. The
      genome-wide analysis revealed several distinct gene clusters with a specific
      pattern of gene regulation for each subset. The largest cluster contained genes
      upregulated after transition through the most primitive pool into the next
      transitory population with a consistently elevated expression of elements
      associated with ongoing T cell fate specification, like Gata3 and Tcf7, in fetal
      progenitors. Furthermore, adult and fetal T cell progenitors occupied distinct
      "transcriptional territories" revealing a precise land map of the progression to
      final T cell commitment operating in different developmental windows. The
      presence and/or elevated expression of elements associated with an ongoing
      establishment of a T cell signature in the most primitive fetal subset is highly
      suggestive for an extrathymic initiation of T cell specification and underlines
      the fundamental differences in fetal versus adult lymphopoiesis.

PMID- 22581010
TI  - Infantile spasms: treatment challenges.
AB  - OPINION STATEMENT: Infantile spasms (IS) represent a major therapeutic challenge,
      as cessation of spasms and normalization of the electroencephalogram (elimination
      of hypsarrhythmia) are mandatory to prevent cognitive deterioration in previously
      healthy infants, or to preserve neurocognitive function among those
      neurologically affected prior to onset of IS. Traditionally, this epilepsy
      syndrome has been considered a "catastrophic" epilepsy, not only for its frequent
      refractoriness, but mostly due to its effect on cognition. Nevertheless, a change
      of attitude among pediatric epileptologists is probably warranted, as enough
      evidence and clinical experience demonstrate that early, aggressive therapy,
      especially with adrenocorticotropic hormone (ACTH), may not only lead to
      cessation of spasms, but often leads to the cure of infants with
      idiopathic/cryptogenic IS. Some ACTH protocols such as that prescribed in Israel
      (tetracosactide ACTH) appear to be highly efficacious in guarantying a good or
      even excellent prognosis in idiopathic IS. Moreover, oral prednisolone is a
      promising and much less expensive alternative to IM ACTH. Vigabatrin does have a
      role as a first-line agent, especially for tuberous sclerosis patients, but
      evidence supports hormonal therapy as the initial treatment. The role of
      pyridoxine and the ketogenic diet still needs to be established; given the
      efficacy of a much shorter tetracosactide ACTH protocol, there may be no need for
      the long-term diet, despite its efficacy. Finally, a very promising drug has been
      developed (CP-115) that may altogether replace the current therapeutic regimens
      in the near future.

PMID- 22581008
TI  - Apoplastic and cytoplasmic location of harpin protein Hpa1Xoo plays different
      roles in H2O2 generation and pathogen resistance in Arabidopsis.
AB  - Harpin proteins secreted by phytopathogenic bacteria have been shown to activate
      the plant defense pathway, which involves transduction of a hydrogen peroxide
      (H(2)O(2)) signal generated in the apoplast. However, the way in which harpins
      are recognized in the pathway and what role the apoplastic H(2)O(2) plays in
      plant defenses are unclear. Here, we examine whether the cellular localization of
      Hpa1(Xoo), a harpin protein produced by the rice bacterial leaf blight pathogen,
      impacts H(2)O(2) production and pathogen resistance in Arabidopsis thaliana.
      Transformation with the hpa1 (Xoo) gene and hpa1 (Xoo) fused to an apoplastic
      localization signal (shpa1 (Xoo)) generated h pa1 (Xoo)- and sh pa1 (Xoo)
      expressing transgenic A . t haliana (HETAt and SHETAt) plants, respectively.
      Hpa1(Xoo) was associated with the apoplast in SHETAt plants but localized inside
      the cell in HETAt plants. In addition, Hpa1(Xoo) localization accompanied
      H(2)O(2) accumulation in both the apoplast and cytoplasm of SHETAt plants but
      only in the cytoplasm of HETAt plants. Apoplastic H(2)O(2) production via
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) located in the
      plasma membrane is a common feature of plant defenses. In SHETAt plants, H(2)O(2)
      was generated in apoplasts in a NOX-dependent manner but accumulated to a greater
      extent in the cytoplasm than in the apoplast. After being applied to the wild
      type plant, Hpa1(Xoo) localized to apoplasts and stimulated H(2)O(2) production
      as in SHETAt plants. In both plants, inhibiting apoplastic H(2)O(2) generation
      abrogated both cytoplasmic H(2)O(2) accumulation and plant resistance to
      bacterial pathogens. These results suggest the possibility that the apoplastic
      H(2)O(2) is subject to a cytoplasmic translocation for participation in the
      pathogen defense.

PMID- 22581011
TI  - Communicating the risks of medicines: time to move forward.

PMID- 22581012
TI  - Warnings without guidance: patient responses to an FDA warning about ezetimibe.
AB  - BACKGROUND: In January 2008, the Food and Drug Administration (FDA) communicated
      concerns about the efficacy of ezetimibe, but did not provide clear clinical
      guidance, and substantial media attention ensued. We investigated the proportion
      of patients who discontinued therapy and switched to a clinically appropriate
      alternative after the FDA communication. METHODS: Using claims data from a
      national pharmacy benefits manager, we created a rolling cohort of new users of
      ezetimibe between January 2006 and August 2008 and created a supply diary for
      each patient in the year after cohort entry. A patient was identified as
      nonpersistent if a gap of 90 days was seen in the diary. Using segmented linear
      regression, we compared rates of nonpersistence before and after the FDA
      communication and assessed patient-level characteristics associated with
      discontinuation. Among nonpersistent patients, we determined whether a patient
      made a clinically appropriate switch in the subsequent 90 days by adding a new
      cholesterol-lowering medication or by increasing the dose of an existing one. We
      used a weighted t test to compare the rates of appropriate switching before and
      after the communication. RESULTS: Among 867,027 new ezetimibe users, 407,006
      (46.9%) were nonpersistent in the first year. After the FDA communication, the
      monthly level of ezetimibe nonpersistence increased by 5.7 percentage points
      (P<0.0001). Younger patients, those who lived in low-income zip codes, and female
      patients were less likely to discontinue therapy (P<0.0001 for all). Among
      nonpersistent patients, rates of clinically appropriate switching increased from
      10.8% before to 16.5% after the FDA warning (P = 0.004). CONCLUSIONS: A
      substantial increase in ezetimibe nonpersistence rates was seen after an FDA
      communication regarding its efficacy and following associated media attention,
      and a small proportion of patients made a clinically appropriate switch after
      discontinuation. Further consideration is needed to deliver messages that promote
      appropriate use of chronic therapy rather than simply reduce use.

PMID- 22581013
TI  - A comparison and cross-validation of models to predict basic activity of daily
      living dependency in older adults.
AB  - BACKGROUND: A simple method of identifying elders at high risk for activity of
      daily living (ADL) dependence could facilitate essential research and
      implementation of cost-effective clinical care programs. OBJECTIVE: We used a
      nationally representative sample of 9446 older adults free from ADL dependence in
      2006 to develop simple models for predicting ADL dependence at 2008 follow-up and
      to compare the models to the most predictive published model. Candidate predictor
      variables were those of published models that could be obtained from interview or
      medical record data. METHODS: Variable selection was performed using logistic
      regression with backward elimination in a two-third random sample (n = 6233) and
      validated in a one-third random sample (n = 3213). Model fit was determined using
      the c-statistic and evaluated vis-a-vis our replication of a published model.
      RESULTS: At 2-year follow-up, 8.0% and 7.3% of initially independent persons were
      ADL dependent in the development and validation samples, respectively. The best
      fitting, simple model consisted of age and number of hospitalizations in past 2
      years, plus diagnoses of diabetes, chronic lung disease, congestive heart
      failure, stroke, and arthritis. This model had a c-statistic of 0.74 in the
      validation sample. A model of just age and number of hospitalizations achieved a
      c-statistic of 0.71. These compared with a c-statistic of 0.79 for the published
      model. Sensitivity analyses demonstrated model robustness. CONCLUSIONS: Models
      based on a widely available data achieve very good validity for predicting ADL
      dependence. Future work will assess the validity of these models using medical
      record data.

PMID- 22581014
TI  - The impact of threshold language assistance programming on the accessibility of
      mental health services for persons with limited English proficiency in the Medi
      Cal setting.
AB  - BACKGROUND: Title VI of the 1964 Civil Rights Act prohibits federal funds
      recipients from providing care to limited English proficiency (LEP) persons more
      limited in scope or lower in quality than care provided to others. In 1999, the
      California Department of Mental Health implemented a "threshold language access
      policy" to meet its Title VI obligations. Under this policy, Medi-Cal agencies
      must provide language assistance programming in a non-English language where a
      county's Medical population contains either 3000 residents or 5% speakers of that
      language. RESEARCH DESIGN: We examine the impact of threshold language policy
      required language assistance programming on LEP persons' access to mental health
      services by analyzing the county-level penetration rate of services for Russian,
      Spanish, and Vietnamese speakers across 34 California counties, over 10 years of
      quarterly data. Exploiting a time series with nonequivalent control group study
      design, we studied this phenomena using linear regression with random county
      effects to account for trends over time. RESULTS: Threshold language policy
      required assistance programming led to an immediate and significant increase in
      the penetration rate of mental health services for Russian (8.2, P < 0.01) and
      Vietnamese (3.3, P < 0.01) language speaking persons. CONCLUSIONS: Threshold
      language assistance programming was effective in increasing mental health access
      for Russian and Vietnamese, but not for Spanish-speaking LEP persons.

PMID- 22581015
TI  - Psychosocial health care needs assessment of adult cancer patients: a consensus
      based guideline.
AB  - PURPOSE: Although recommended as an essential part of cancer care, there is
      limited evidence regarding the optimum approach to psychosocial health care needs
      assessment in this setting. To address this gap, the Cancer Journey Action Group
      of the Canadian Partnership Against Cancer (CPAC) and the Canadian Association of
      Psychosocial Oncology (CAPO) partnered to develop consensus-based recommendations
      regarding the routine assessment of psychosocial and supportive care needs. The
      purpose of this paper is to summarize the evidence that informed the guideline
      and disseminate the recommendations developed by the expert panel. METHODS:
      Clinical practice recommendations were developed by a panel comprised of
      psychosocial and interdisciplinary experts. Recommendations were informed by a
      review of oncology clinical practice guidelines, systematic reviews, and primary
      research, through to May 2008. Following expert consensus on the recommendations,
      the clinical practice guideline was externally reviewed by a purposively selected
      sample of national and international interdisciplinary experts. RESULTS: A total
      of nine clinical practice guidelines, three systematic reviews, and 14 primary
      studies were included in the review. Overall, this body of literature suggested
      that routine collection of psychosocial health care data has an influence on
      communication with oncologists and other study specific outcomes, but the
      evidence was limited by heterogeneity and methodological limitations. Based on
      the interpretation of this body of evidence by clinical experts, research
      methodologists, and external reviewers, 12 substantive recommendations were
      developed regarding the process and parameters of psychosocial needs assessment
      in adult cancer patients. CONCLUSION: Given the limitations in the current body
      of evidence, there remains a need for rigorous empirical research regarding the
      optimal approach to psychosocial needs assessment, including the specific
      characteristics that influence effectiveness on patient outcomes. This guideline
      fills an important gap in psychosocial care, regarding the routine assessment of
      psychosocial health care needs.

PMID- 22581016
TI  - Heritability of alcohol dependence is similar in women and men.

PMID- 22581017
TI  - Review: antidepressants are effective for the treatment of major depressive
      disorder in individuals aged 55 years or older.

PMID- 22581018
TI  - Review: methylphenidate and atomoxetine have similar efficacy and acceptability
      in children and adolescents with ADHD.

PMID- 22581019
TI  - Long working hours are associated with incident depressive and anxiety symptoms
      in women.

PMID- 22581020
TI  - Distribution and risk assessment of organochlorine contaminants in surface water
      from River Chenab, Pakistan.
AB  - Concentrations in surface waters (including particulate phase) of the River
      Chenab ranged from 27-1100 ng L(-1) and 25-1200 ng L(-1) for OCPs and 7.7-110 ng
      L(-1) and 13-99 ng L(-1) for PCBs during summer and winter, respectively from
      2007-2009. DDTs exhibited the highest concentration, followed by HCHs > chlordane
      > ?(24)PCBs > ?other OCPs. Different indicative ratios for organochlorines
      suggest that current use, long range transport and also past application of these
      chemicals contribute to the total burden. Statistical analysis highlighted
      agricultural and industrial activities and municipal waste disposal as main
      sources of OCPs and PCBs in the riverine ecosystem of the River Chenab. Risk
      Quotients (RQ(CCCs)) > 10 for DDTs and PCBs levels in collected water samples
      from the River Chenab suggest that risk from DDTs and PCBs is moderate to severe
      and fluxes calculated for OCPs and PCBs from the River Chenab to the Indus River
      were 7.5 tons per year and 1.0 tons per year, respectively.

PMID- 22581021
TI  - Mortality meets: learning beyond life.

PMID- 22581023
TI  - First-principles study of bandgap effects in graphene due to hydrogen adsorption.
AB  - Hydrogen adsorption on graphene in commensurate periodic arrangements leads to
      bandgap opening at the Dirac point and the emergence of dispersionless midgap
      bands. We study these bandgap effects and their dependence on periodicity for a
      single hydrogen adsorbate on periodic graphene supercells using spin-polarized
      density-functional theory calculations. Our results show that for certain
      periodicities, marked by a scale factor of three, the bandgap is suppressed to a
      great extent, and has a special level structure around the neutrality point. We
      present explanations for the origin of the changes to the band structure in terms
      of the ab initio Hamiltonian matrix. This method may be used to obtain a more
      accurate tight-binding description of single hydrogen adsorption on graphene.

PMID- 22581022
TI  - Effect of nutritional status on Tuberculin skin testing.
AB  - OBJECTIVES: To evaluate Tuberculin skin test (TST) results in a population of
      immigrants and internationally adopted children from several geographical areas;
      to analyze whether nutritional status can modify TST results. METHODS: This cross
      sectional observational study included adopted children and immigrants evaluated
      in the authors' unit between January 2003 and December 2008. Children diagnosed
      with tuberculosis, or vaccinated with live attenuated virus 2 mo earlier, HIV
      infected, chronically ill or under treatment with immunosuppressive agents were
      excluded. TST was considered as dependent variable. Independent variables were
      gender, age, geographical origin, BCG scar, nutritional status, immune status and
      intestinal parasitism. RESULTS: One thousand seventy four children were included;
      69.6 % were girls. There was a BCG scar in 79 % of children. Mantoux = 0 mm was
      found in 84.4 %, <10 mm in 4.1 %, and >=10 mm in 11.4 % of children. Nutrition
      (McLaren's classification) was normal (>=90 %) in 26.7 % of the subjects, with
      mild malnutrition (80-89 %) in 36 %, moderate (70-79 %) in 23.2 % and severe
      (<=69 %) in 14.1 %. There was no difference in TST results among different
      nutritional status children. CONCLUSIONS: The nutritional status, measured by
      McLaren's classification, does not changes the results of TST. McLaren's
      classification only grades protein-caloric malnutrition, so in authors'
      experience this type of malnutrition does not interfere with TST results.
      Implementing other nutritional parameters could help to determine whether
      nutritional status should be taken into account when interpreting TST results.

PMID- 22581024
TI  - Late-onset fracture-associated osteosarcoma in a cat.
AB  - An 18-year-old male, castrated Domestic Shorthaired cat was presented with the
      complaint of acute severe lameness of the left pelvic limb. There was no history
      of trauma, apart from a distal physeal left femoral fracture that had been
      repaired 17 years previously. Radiology revealed a displaced distal metaphyseal
      femoral fracture with marked areas of bone lysis and periosteal proliferations. A
      pathological fracture due to a bone neoplasia was suspected. An amputation with
      coxofemoral disarticulation was performed. Histopathology confirmed the tentative
      diagnosis of appendicular osteo-sarcoma. No postoperative complications were
      encountered and the cat made a full recovery. This case shows an unusual
      presentation of a late-onset fracture-associated feline osteosarcoma.

PMID- 22581025
TI  - Isolation and characterization of proliferative, migratory and multidrug
      resistant endometrial carcinoma-initiating cells from human type II endometrial
      carcinoma cell lines.
AB  - Although the highly proliferative, migratory and multidrug resistant phenotype of
      human type II endometrial carcinoma (EC) is well characterized, improved clinical
      treatments have not yet been developed. In this study, CD44 and CD133 were used
      as markers to screen, isolate and enrich carcinoma-initiating cells (CICs) from
      the human type II EC cell lines KLE and ANCA3. Using flow cytometry, we
      identified a subpopulation of KLE and ANCA3 cells which express high levels of
      both CD44 and CD133 on the cell membrane. CD44+/CD133+ EC-CICs exhibited high
      levels of stemness marker genes, and possessed a higher migratory and invasive
      ability than CD44-/CD133- endometrial carcinoma cells (EC-CCs). CD44+/CD133+ EC
      CICs were also more resistant to growth inhibition induced by the
      chemotherapeutic drugs cisplatin and paclitaxel. Additionally, CD44+/CD133+ EC
      CICs readily established tumors in vivo in a relatively short time. In
      conclusion, CD44+/CD133+ cells possessing the characteristics of CICs can be
      reliably sorted from KLE and ANCA3 human type II EC cell lines, and represent a
      valuable model for studying cancer cell physiology and multidrug resistance.
      Further characterization of CD44+/CD133+ KLE and ANCA3 cells may have a profound
      impact on the selection of individual treatment strategies, clinical outcomes and
      design of the next generation of chemotherapeutic agents for type II EC.

PMID- 22581026
TI  - Recognizing recurrent neural networks (rRNN): Bayesian inference for recurrent
      neural networks.
AB  - Recurrent neural networks (RNNs) are widely used in computational neuroscience
      and machine learning applications. In an RNN, each neuron computes its output as
      a nonlinear function of its integrated input. While the importance of RNNs,
      especially as models of brain processing, is undisputed, it is also widely
      acknowledged that the computations in standard RNN models may be an over
      simplification of what real neuronal networks compute. Here, we suggest that the
      RNN approach may be made computationally more powerful by its fusion with
      Bayesian inference techniques for nonlinear dynamical systems. In this scheme, we
      use an RNN as a generative model of dynamic input caused by the environment, e.g.
      of speech or kinematics. Given this generative RNN model, we derive Bayesian
      update equations that can decode its output. Critically, these updates define a
      'recognizing RNN' (rRNN), in which neurons compute and exchange prediction and
      prediction error messages. The rRNN has several desirable features that a
      conventional RNN does not have, e.g. fast decoding of dynamic stimuli and
      robustness to initial conditions and noise. Furthermore, it implements a
      predictive coding scheme for dynamic inputs. We suggest that the Bayesian
      inversion of RNNs may be useful both as a model of brain function and as a
      machine learning tool. We illustrate the use of the rRNN by an application to the
      online decoding (i.e. recognition) of human kinematics.

PMID- 22581027
TI  - Notch receptor-ligand interactions during T cell development, a ligand
      endocytosis-driven mechanism.
AB  - Notch signaling plays an important role during the development of different cell
      types and tissues. The role of Notch signaling in lymphocyte development, in
      particular in the development and commitment to the T cell lineage, has been the
      focus of research for many years. Notch signaling is absolutely required during
      the commitment and early stages of T cell development. Activation of the Notch
      signaling pathway is initiated by ligand-receptor interactions and appears to
      require active endocytosis of Notch ligands. Studies addressing the mechanism
      underlying endocytosis of Notch ligands have helped to identify the main players
      important and necessary for this process. Here, we review the Notch ligands, and
      the proposed models of Notch activation by Notch ligand endocytosis, highlighting
      key molecules involved. In particular, we discuss recent studies on Notch ligands
      involved in T cell development, current studies aimed at elucidating the
      relevance of Notch ligand endocytosis during T cell development and the
      identification of key players necessary for ligand endocytosis in the thymus and
      during T cell development.

PMID- 22581028
TI  - Screening of significantly hypermethylated genes in breast cancer using
      microarray-based methylated-CpG island recovery assay and identification of their
      expression levels.
AB  - To screen candidate methylation markers for early detection of breast cancer and
      to explore the relationship between methylation and gene expression, we performed
      methylated-CpG island recovery assay (MIRA) combined with CpG island array on
      61982 CpG sites across 4162 genes in 10 cancerous and 10 non-cancerous breast
      tissues. Direct bisulfite sequencing and combined bisulfite restriction analysis
      (COBRA) were carried out in independent cancerous and non-cancerous samples. Gene
      expression was analyzed by microarrays and validated using RT-PCR. We detected 70
      significantly hypermethylated genes in breast cancer tissues, including many
      novel hypermethylated genes such as ITGA4, NFIX, OTX2 and FGF12. Direct bisulfite
      sequencing showed widespread methylation occurring in intragenic regions of the
      WT1, PAX6 and ITGA4 genes and in the promoter region of the OTX2 gene in breast
      cancer tissues. COBRA assay confirmed that the WT1, OTX2 and PAX6 genes were
      hypermethylated in breast cancer tissues. Clustering analysis of the gene
      expression of 70 significantly hypermethylated genes revealed that most
      hypermethylated genes in breast cancer were not expressed in breast tissues. RT
      PCR assay confirmed that WT1 and PITX2 were only weakly expressed in the breast
      cancer tissues and were not expressed in most non-cancerous breast tissues. OTX2
      and PAX6 were not expressed in either breast cancer or non-cancerous tissues. In
      conclusion, these results will expand our knowledge of hypermethylated genes and
      methylation sites for early detection of breast cancer and deepen our
      understanding of the relationship between methylation and gene expression. The
      MIRA approach can screen candidate methylated genes for further clinical
      validation more effectively than gene expression microarray-based strategy.

PMID- 22581030
TI  - Seven essential strategies for promoting and sustaining systemic cultural
      competence.
AB  - Racial and ethnic disparities are disturbing facets of the American healthcare
      system that document the reality of unequal treatment. Research consistently
      shows that patients of color experience poorer quality of care and health
      outcomes contributing to increased risks and accelerated mortality rates relative
      to their white counterparts. While initially conceptualized as an approach for
      increasing the responsiveness of children's behavioral health care, cultural
      competence has been adopted as a key strategy for eliminating racial and ethnic
      health disparities across the healthcare system. However, cultural competence
      research and practices largely focus on improving provider competencies, while
      agency and system level approaches for meeting the service needs of diverse
      populations are given less attention. In this article we offer seven essential
      strategies for promoting and sustaining organizational and systemic cultural
      competence. These strategies are to: (1) Provide executive level support and
      accountability, (2) Foster patient, community and stakeholder participation and
      partnerships, (3) Conduct organizational cultural competence assessments, (4)
      Develop incremental and realistic cultural competence action plans, (5) Ensure
      linguistic competence, (6) Diversify, develop, and retain a culturally competent
      workforce, and (7) Develop an agency or system strategy for managing staff and
      patient grievances. For each strategy we offer several recommendations for
      implementation.

PMID- 22581029
TI  - Differences in seclusion rates between admission wards: does patient compilation
      explain?
AB  - Comparison of seclusion figures between wards in Dutch psychiatric hospitals
      showed substantial differences in number and duration of seclusions. In the
      opinion of nurses and ward managers, these differences may predominantly be
      explained by differences in patient characteristics, as these are expected to
      have a large impact on these seclusion rates. Nurses assume more admissions of
      severely ill patients are related to higher seclusion rates. In order to test
      this hypothesis, we investigated differences in patient and background
      characteristics of 718 secluded patients over 5,097 admissions on 29 different
      admission wards over seven Dutch psychiatric hospitals. We performed an extreme
      group analysis to explore the relationship between patient and ward
      characteristics and the wards' number of seclusion hours per 1,000 admission
      hours. In a multivariate and a multilevel analysis, various characteristics
      turned out to be related to the number of seclusion hours per 1,000 admission
      hours as well as to the likelihood of a patient being secluded, confirming the
      nurses assumptions. The extreme group analysis showed that seclusion rates
      depended on both patient and ward characteristics. A multivariate and multilevel
      analyses revealed that differences in seclusion hours between wards could
      partially be explained by ward size next to patient characteristics. However, the
      largest deal of the difference between wards in seclusion rates could not be
      explained by characteristics measured in this study. We concluded ward policy and
      adequate staffing may, in particular on smaller wards, be key issues in reduction
      of seclusion.

PMID- 22581031
TI  - The status of antimicrobial resistance of Helicobacter pylori in Eastern
      Azerbaijan, Iran: comparative study according to demographics.
AB  - Helicobacter pylori-associated infections are extremely common in Iran, but few
      data about antibiotic sensitivity of H. pylori are available for this region. The
      purpose of this study was to investigate the prevalence of resistance in isolates
      against commonly used antibiotics in Eastern Azerbaijan, Iran, and the dependence
      of prevalence on the sex and age of patients. H. pylori isolates were collected
      by culture from gastric biopsies. Antibiotic susceptibility of isolates was
      determined by use of the disk agar diffusion test, and the minimum inhibitory
      concentration of clarithromycin was established by use of the Etest. A total 395
      of biopsy specimens were studied; 112 samples of H. pylori were isolated (28.3
      %), 55 (49 %) from males and 57 (51 %) from females. The prevalence of resistance
      to clarithromycin, metronidazole, erythromycin, amoxicillin, ciprofloxacin,
      rifampin, nitrofurantoin, and tetracycline were 16 (14.3 %), 86 (76.8 %), 29
      (26.0 %), 32 (28.6 %), 37 (33.0 %), 32 (28.6 %), 13 (11.6 %), and 21 (18.7 %),
      respectively. Antimicrobial resistance was not statistically significantly
      associated with sex or age. Furthermore, the prevalence of resistance to
      metronidazole was high and that to clarithromycin was reasonable, consistent with
      reported low success in H. pylori treatment in this area. Therefore, continuous
      surveillance of antibiotic resistance of H. pylori is essential.

PMID- 22581032
TI  - Personal hair dye use and the risk of bladder cancer: a case-control study from
      The Netherlands.
AB  - BACKGROUND: Several studies have suggested an increased risk of bladder cancer
      among hairdressers, who are occupationally exposed to hair dyes. There has also
      been concern about a possible increased risk of bladder cancer among users of
      hair dyes. However, the association between personal hair dye use and bladder
      cancer risk remains inconclusive. OBJECTIVE: In this study, we examined
      associations between personal use of permanent and temporary hair dyes and
      bladder cancer risk in a population-based case-control study involving 1,385
      cases (n = 246 women) and 4,754 controls (n = 2,587 women). METHODS: Participants
      filled out a questionnaire with regard to history of personal hair dye use and
      risk factors for bladder cancer. Unconditional logistic regression was used to
      calculate odds ratios (OR) and 95 % confidence intervals (CI), adjusted for age,
      smoking status, duration of smoking and intensity of smoking. RESULTS: Analyses
      were restricted to women as less than 5 % of all men in the study ever used hair
      dyes. About 50 % of the women ever used hair dyes. Use of temporary hair dyes
      (OR, 0.77; 95 % CI, 0.58-1.02) or use of permanent hair dyes (OR, 0.87; 95 % CI,
      0.65-1.18) was not associated with bladder cancer risk. No clear association
      between hair dyes and bladder cancer risk was found when dye use was defined by
      type, duration or frequency of use, dye color, or extent of use. Also, results
      were similar for aggressive- and non-aggressive bladder cancer. Age, educational
      level, and smoking status did not modify the association between hair dye use and
      bladder cancer risk. CONCLUSIONS: The present study does not support an
      association between personal hair dye use and bladder cancer risk. Also, various
      types of hair dye, intensity of exposure to hair dyes or dye color do not appear
      to be important factors for bladder cancer development.

PMID- 22581033
TI  - Hyperoxia management during deep hypothermia for cerebral protection in
      circulatory arrest rabbit model.
AB  - As a brain protection strategy, antegrade selective cerebral perfusion (ASCP) is
      widely used in thoracic aorta surgery with deep hypothermic circulatory arrest
      (DHCA), yet the oxygen management for ASCP has never been standardized. The aim
      of this study was to investigate the possible neuroprotective effects of
      hyperoxia management during deep hyperthermia for ASCP combined with DHCA in a
      rabbit model. Rabbits were assigned into four groups: sham group, without
      cardiopulmonary bypass (CPB); DHCA group, DHCA for 80 minutes; ASCP group, ASCP
      combined with DHCA; and SH group, hyperoxia management combined with ASCP and
      DHCA. Hyperoxia management was performed when the nasopharyngeal temperature was
      below 22 degrees C. Deep hypothermic circulatory arrest was initiated when
      nasopharyngeal temperature reached 16-18 degrees C. Blood samples were withdrawn
      to determine blood gas indexes and neurobiochemical markers of damage, and brain
      tissues were stored for biochemical analysis. Cerebral oxygen balance was
      performed better in the SH group compared with the DHCA group and the ASCP group.
      Hyperoxia management did not increase lipid peroxidation with lower
      malondialdehyde levels in the SH group compared with the DHCA group and the ASCP
      group (p < 0.05). S100 calcium binding protein B in the SH group was lower
      compared with the DHCA group and the ASCP group (p < 0.05). There was no
      significant difference of neuron-specific enolase in the SH group compared with
      the sham group. Hyperoxia management during deep hypothermia provided substantial
      dissolved oxygen and demonstrated better cerebral protection over normoxia
      management.

PMID- 22581034
TI  - Hemodynamic design requirements for in-series thoracic artificial lung attachment
      in a model of pulmonary hypertension.
AB  - Recent thoracic artificial lung (TAL) prototypes have impedances lower than the
      natural lung. With these devices, proximal pulmonary artery (PA) to distal PA TAL
      attachment may be possible in patients without right ventricular dysfunction.
      This study examined the relationship between pulmonary system impedance and
      cardiac output (CO) to create TAL design constraints. A circuit with adjustable
      resistance and compliance (C) was attached in a PA-PA fashion with the pulmonary
      circulation of seven sheep with chronic pulmonary hypertension. The pulmonary
      system zeroth harmonic impedance modulus (Z(0)) was increased by 1, 2.5, and 4
      mmHg/(L/min) above baseline. At each Z(0), C was set to 0, 0.34, and 2.1 ml/mmHg.
      The change in pulmonary system zeroth and first harmonic impedance moduli
      (DeltaZ(0) and DeltaZ(1)), the percent change in CO (%DeltaCO), and the inlet and
      outlet anastomoses resistances were calculated for each situation. Results
      indicate that DeltaZ(0) (p < 0.001) but not DeltaZ(1) (p = 0.5) had a significant
      effect on %DeltaCO and that %DeltaCO = -7.45*DeltaZ(0) (R(2) = 0.57). Inlet and
      outlet anastomoses resistances averaged 0.77 +/- 0.16 and 0.10 +/- 0.19
      mmHg/(L/min), respectively, and the relationship between %DeltaCO and TAL
      resistance, R(T), in mmHg/(L/min) was determined to be %DeltaCO = -(7.45f)*(R(T)
      + 0.87), in which f = the fraction of CO through the TAL. Thus, newer TAL designs
      can limit %DeltaCO to less than 10% if f < 0.75.

PMID- 22581035
TI  - Femur mass in a 43-year-old woman.

PMID- 22581036
TI  - Effect of impurities in biodiesel-derived waste glycerol on the performance and
      feasibility of biotechnological processes.
AB  - The rapid development of biodiesel production technology has led to the
      generation of tremendous quantities of glycerol wastes, as the main by-product of
      the process. Stoichiometrically, it has been calculated that for every 100 kg of
      biodiesel, 10 kg of glycerol are produced. Based on the technology imposed by
      various biodiesel plants, glycerol wastes may contain numerous kinds of
      impurities such as methanol, salts, soaps, heavy metals, and residual fatty
      acids. This fact often renders biodiesel-derived glycerol unprofitable for
      further purification. Therefore, the utilization of crude glycerol though
      biotechnological means represents a promising alternative for the effective
      management of this industrial waste. This review summarizes the effect of various
      impurities-contaminants that are found in biodiesel-derived crude glycerol upon
      its conversion by microbial strains in biotechnological processes. Insights are
      given concerning the technologies that are currently applied in biodiesel
      production, with emphasis to the impurities that are added in the composition of
      crude glycerol, through each step of the production process. Moreover, extensive
      discussion is made in relation with the impact of the nature of impurities upon
      the performances of prokaryotic and eukaryotic microorganisms, during crude
      glycerol bioconversions into a variety of high added-value metabolic products.
      Finally, aspects concerning ways of crude glycerol treatment for the removal of
      inhibitory contaminants as reported in the literature are given and
      comprehensively discussed.

PMID- 22581037
TI  - Yeast cells as microcapsules. Analytical tools and process variables in the
      encapsulation of hydrophobes in S. cerevisiae.
AB  - Yeast cells can be used as biocompatible and biodegradable containers for the
      microencapsulation of a variety of actives. Despite the wide application of this
      process, e.g. in the food industry, mechanism and controlling factors are yet
      poorly known. In this study we have studied kinetics and mechanistic aspects of
      the spontaneous internalization of terpenes (as model hydrophobic compounds) in
      Saccharomyces cerevisiae, quantifying their encapsulation through HPLC analysis
      and fluorescent staining of lipidic bodies with Nile Red, while in parallel
      monitoring cell viability. Our results showed that this encapsulation process is
      essentially a phenomenon of passive diffusion with negligible relevance of active
      transport. Further, our evidence shows that the major determinant of the
      encapsulation kinetics is the solubility of the hydrophobe in the cell wall,
      which is inversely related to partition coefficient (log P).

PMID- 22581038
TI  - Decision support for optimized blood glucose control and nutrition in a
      neurotrauma intensive care unit: preliminary results of clinical advice and
      prediction accuracy of the Glucosafe system.
AB  - Assessment of glycemic control with model-based decision support ("Glucosafe") in
      neurotrauma intensive care patients in an ongoing randomized controlled trial
      with a blood glucose (BG) target of 5-8 mmol/L. Assessment of BG prediction
      accuracy of the model and assessment of the effect that two potential model
      extensions would have on prediction accuracy in this trial. In the intervention
      group insulin infusion rates and nutrition are varied based on Glucosafe's
      decision support. In the control group, the caloric target is 25-30 kcal/kg per
      day and insulin is regulated according to department rules. BG concentrations,
      insulin infusion rates, and feed rates are compared from the data of 12
      consecutive patients. BG measurements are predicted retrospectively and the mean
      relative prediction error is calculated using (1) the current model from the
      trial, (2) the current model modified by using a BG-dependent variable endogenous
      insulin appearance rate, (3) the current model modified by a patient-specific
      carbohydrate absorption factor. BG control was improved by Glucosafe. 76 % of BG
      measurements in Glucosafe patients were in the 5-8 mmol/L band (Controls: 51 %).
      BG means (log-normal) +/- SD were 7.0 +/- 1.19 mmol/L in Glucosafe patients
      compared to 8.0 +/- 1.24 mmol/L in controls (P = 0.05). Mean caloric intake was
      93.5 +/- 15 % of resting energy expenditure in Glucosafe patients (Controls: 129
      +/- 29 %). The BG-dependent variable insulin appearance rate had no measurable
      effect on prediction accuracy. The patient-specific carbohydrate absorption
      factor improved prediction accuracy significantly (P = 0.001). Glucosafe advice
      reduces hyperglycemia in neurotrauma intensive care patients. Further
      parameterization can improve model prediction accuracy.

PMID- 22581039
TI  - Validation of the new intubation detector device: a manikin study.
AB  - This study was done to validate the utility of Umesh's intubation detector in
      detection of tracheal or oesophageal intubation in manikin using volunteers with
      different levels of experience in tracheal intubation (including novices). The
      Sim Man II, (Laerdal Medical AS, Norway) manikin was used. Two cuffed tracheal
      tubes of size 6.5 mm ID were used. One was passed into the trachea and the other
      into oesophagus. The device was connected to one of the two tubes as per
      randomisation table and three high quality chest compressions were performed.
      Each volunteer participated in the study twice. Their opinion regarding the tube
      position (in trachea or oesophagus or could not determine) was noted. A total of
      50 volunteers participated in the study. Eleven of them had not observed
      intubation (novice), 29 had either only observed or had experience of <10
      tracheal intubations (less experienced) and 10 had experience of >10 intubations
      or >1 year experience in tracheal intubation (experienced). Out of a total 100
      performances, 99 were correctly identified. On one instance, a tube placed in
      trachea was incorrectly interpreted to be in the oesophagus by a novice. Umesh's
      intubation detector helps in rapid and reliable confirmation of tracheal
      intubation in manikin irrespective of the experience level of the assessor in
      tracheal intubation.

PMID- 22581040
TI  - Critical role of c-Kit in beta cell function: increased insulin secretion and
      protection against diabetes in a mouse model.
AB  - AIMS/HYPOTHESIS: The receptor tyrosine kinase, c-Kit, and its ligand, stem cell
      factor, control a variety of cellular processes, including pancreatic beta cell
      survival and differentiation as revealed in c-Kit ( Wv ) mice, which have a point
      mutation in the c-Kit allele leading to loss of kinase activity and develop
      diabetes. The present study further investigated the intrinsic role of c-Kit in
      beta cells, especially the underlying mechanisms that influence beta cell
      function. METHODS: We generated a novel transgenic mouse model with c-KIT
      overexpression specifically in beta cells (c-KitbetaTg) to further examine the
      physiological and functional roles of c-Kit in beta cells. Isolated islets from
      these mice were used to investigate the underlying molecular pathway of c-Kit in
      beta cells. We also characterised the ability of c-Kit to protect animals from
      high-fat-diet-induced diabetes, as well as to rescue c-Kit ( Wv ) mice from early
      onset of diabetes. RESULTS: c-KitbetaTg mice exhibited improved beta cell
      function, with significantly improved insulin secretion, and increased beta cell
      mass and proliferation in response to high-fat-diet-induced diabetes. c-KitbetaTg
      islets exhibited upregulation of: (1) insulin receptor and IRSs; (2) Akt and
      glycogen synthase kinase 3beta phosphorylation; and (3) transcription factors
      important for islet function. c-KIT overexpression in beta cells also rescued
      diabetes observed in c-Kit ( Wv ) mice. CONCLUSIONS/INTERPRETATION: These
      findings demonstrate that c-Kit plays a direct protective role in beta cells, by
      regulating glucose metabolism and beta cell function. c-Kit may therefore
      represent a novel target for treating diabetes.

PMID- 22581041
TI  - Central nervous system endoplasmic reticulum stress in a murine model of type 2
      diabetes.
AB  - AIMS/HYPOTHESIS: Type 2 diabetes is associated with complications in the central
      nervous system (CNS), including learning and memory, and an increased risk for
      neurodegenerative diseases. The mechanism underlying this association is not
      understood. The aim of this study was to gain greater insight into the possible
      mechanisms of diabetes-induced cognitive decline. METHODS: We used microarray
      technology to identify and examine changes in gene expression in the hippocampus
      of a murine model of type 2 diabetes, the db/db mouse. Bioinformatics approaches
      were then used to investigate the biological significance of these genes. To
      validate the biological significance we evaluated mRNA and protein levels.
      RESULTS: At 8 and 24 weeks, 256 and 822 genes, respectively, were differentially
      expressed in the db/db mice. The most significantly enriched biological functions
      were related to mitochondria, heat shock proteins, or the endoplasmic reticulum
      (ER), the majority of which were downregulated. The ER-enriched cluster was one
      of the clusters that contained the highest number of differentially expressed
      genes. Several of the downregulated genes that were differentially expressed at
      24 but not at 8 weeks are directly involved in the unfolded protein response
      (UPR) pathway and include two heat shock proteins (encoded by Hspa5 and Hsp90b1),
      a transcriptional factor (x-box binding protein 1, encoded by Xbp1), and an
      apoptotic mediator (DNA-damage inducible transcript 3, encoded by Ddit3).
      CONCLUSIONS/INTERPRETATION: The changes that we observed in the UPR pathway due
      to ER stress may play a role in the pathogenesis of CNS complications in
      diabetes. The results of this study are a foundation for the development of
      pharmacological targets to reduce ER stress in diabetic hippocampi.

PMID- 22581042
TI  - Interferon-gamma modulates the functional profile of in-vitro-cultured porcine
      microglia.
AB  - Microglia are the most important immune cells within the highly specialized
      environment of the central nervous system. Upon activation, they transform from a
      resting 'ramified' into a fully functional 'amoeboid' phenotype with the ability
      to perform phagocytosis and generate free radicals. A combined flow cytometric
      assay for the simultaneous measurement of these two functions in porcine
      microglia in vitro is presented: reactive oxygen species are detected using
      hydroethidine; phagocytosis is assessed using fluorescein isothiocyanate-labeled
      latex beads. The combination of these two probes allowed us to distinguish four
      subpopulations within cultured porcine microglia on the basis of their functional
      activity. The effect of several exogenous stimuli [phorbol myristate acetate,
      conditioned medium, interferon gamma (IFN-gamma)] on the in-vitro functional
      properties of porcine microglia is investigated using this test. In particular
      for IFN-gamma, a significant modulatory effect on the intracellular reactive
      oxygen species production and phagocytic activity was observed. This result
      suggests an alternative role of IFN-gamma acting on cultured porcine microglia.

PMID- 22581043
TI  - Expression of P2X3 and TRPV1 receptors in primary sensory neurons from estrogen
      receptors-alpha and estrogen receptor-beta knockout mice.
AB  - In women, pain symptoms and nociceptive thresholds vary with the reproductive
      cycle, suggesting the role of estrogen receptors (ERs) in modulating nociception.
      Our previous data strongly suggest an interaction between ERs and ATP-induced
      purinergic (P2X3) as well as ERs and capsaicin-induced vanilloid (TRPV1)
      receptors at the level of dorsal root ganglion (DRG) neurons. In this study, we
      investigated the expression of P2X3 and TRPV1 receptors by western blotting and
      immunohistochemistry in lumbosacral DRGs from wild type, ERalpha, and ERbeta
      knockout mice. We found a significant decrease for both P2X3 and TRPV1 in
      ERalphaKO and ERbetaKO. This phenomenon was visualized in L1, L2, L4, and L6
      levels for P2X3 receptors and in L1, L2, and S2 levels for TRPV1 receptors. This
      tan interaction between P2X3/TRPV1 and ERs expression in sensory neurons may
      represent a novel mechanism that can explain the sex differences in nociception
      observed in clinical practice. The DRG is an important site of visceral afferent
      convergence and cross-sensitization and a potential target for designing new anti
      nociceptive therapies.

PMID- 22581044
TI  - alpha-Synuclein expression is modulated at the translational level by iron.
AB  - Several studies have suggested an interaction between alpha-synuclein protein and
      iron in Parkinson's disease. The presence of iron together with alpha-synuclein
      in Lewy bodies, the increase of iron in the substantia nigra and the correlation
      between polymorphism of the several genes implicated in iron metabolism and
      Parkinson's disease, support a role for iron in the neurodegeneration. Analysis
      of post mortem brains revealed increased amount of insoluble alpha-synuclein
      protein despite unchanged/reduced levels of alpha-synuclein mRNA in Parkinson's
      disease. Interestingly, on the basis of the presence of a putative iron
      responsive element in the 5'-UTR, it has been suggested that there is a possible
      iron-dependent translational control of human alpha-synuclein mRNA. Considering
      the similarity between the sequences present in human alpha-synuclein mRNA and
      the ferritin iron responsive element, we postulated that iron deficiency would
      decrease the translation of alpha-synuclein mRNA. Here we used HEK293 cells
      treated with iron chelator deferoxamine or ferric ammonium citrate to verify the
      possible iron-dependent translational control of human alpha-synuclein
      biosynthesis. We show that the amount of polysome-associated endogenous human
      alpha-synuclein mRNA decreases in presence of deferoxamine. Our data demonstrate
      that human alpha-synuclein expression is regulated by iron mainly at the
      translational level. This result not only supports a role for iron in the
      translational control of alpha-synuclein expression, but also suggests that iron
      chelation may be a valid approach to control alpha-synuclein levels in the brain.

PMID- 22581045
TI  - [Blepharoplasty].

PMID- 22581046
TI  - [Results with the Boston keratoprosthesis].
AB  - BACKGROUND: The Boston keratoprosthesis (BKP) is a surgical therapeutic option in
      patients with corneal disease and poor prognosis for penetrating keratoplasty.
      The purpose of this study was to summarize our results with this surgical
      technique which we have employed at our institution since November 2009. METHODS:
      All patients who underwent the BKP procedure at our institution between November
      2009 and August 2011 were identified retrospectively and the data were analyzed.
      The surgical procedure and postoperative treatment were performed following the
      recommendations of the developers of the BKP. RESULTS: A total of 14 patients
      were included in the study and the patient age ranged from 36 to 78 years. All
      patients had superficial and stromal corneal opacification with loss of the
      normal corneal surface (conjunctivalization). In 13 patients the BKP was
      implanted after at least 1 penetrating keratoplasty (including 3 matched grafts)
      and in 1 patient it was performed as a primary procedure. The underlying diseases
      were Stevens-Johnson syndrome, chemical injury, chronic atopic dermatitis in
      neurodermitis, keratoconus, granulomatous uveitis, congenital glaucoma and
      eyeball injury/burn. The follow-up ranged from 1 to 21 months. Postoperative
      complications consisted of prolonged inflammatory anterior chamber reaction with
      synechia, deposits on the intraocular lens, posterior capsule opacification,
      secondary glaucoma, hypotension, conjunctival growth over the keratoprosthesis
      and cystoid macular edema. All cases had overall improvement of visual acuity at
      the last follow-up visit. The maximum improvement was from counting fingers to
      0.7. CONCLUSION: Until now all BKPs have been preserved. At our institution the
      BKP is becoming increasingly more important even in such cases with a (very) poor
      prognosis for matched limbal and/or corneal grafts. Reimbursement for the BKP
      must, however be organized on a case by case basis.

PMID- 22581047
TI  - [Cataract surgery outcomes by temporal small incision techniques with and without
      phacoemulsification. Results of a prospective study from Kenya].
AB  - BACKGROUND: The present outcomes of cataract surgery in Africa do not meet the
      recommendations of the World Health Organization. Superior manual small incision
      cataract surgery (SICS) is the operation of choice in many developing countries.
      However, there is good evidence that temporal incisions are more stable and cause
      less surgically induced astigmatism (SIA). METHODS: In a prospective, non
      randomized study in an anterior segment clinic in the southeastern part of Kenya,
      405 eyes were operated on using either temporal phacoemulsification (n = 288) or
      temporal SICS (n = 117) with implantation of a rigid intraocular lens (IOL). The
      main outcome variables were preexisting corneal astigmatism, SIA, visual outcomes
      and complication rates. RESULTS: Preoperatively, the mean astigmatism in all eyes
      was 1.1 diopters (D) ranging from 0 to 6.28 D. Against-the-rule astigmatism (ATR)
      (mean 1.18 D) was most common with 60.4%. After 8 weeks following  surgery the
      mean SIA was 1.13 D (SD +/-0.63 D) at 92 degrees  for phacoemulsification and
      1.11 D (SD +/-0.56 D) at 102 degrees  for SICS. Of the eyes 89.6% reached a best
      corrected visual acuity (BCVA)  >= 0.3 and 82.7% reached this visual acuity also
      uncorrected. The main reasons for not reaching BCVA >= 0.3 were ocular
      comorbidities. CONCLUSIONS: In the population studied most patients had
      preexisting ATR astigmatism and a switch to routine temporal incisions appeared
      beneficial. The World Health Organization recommends that poor (BCVA below 0.1)
      or borderline (BCVA below 0.3) outcomes after cataract surgery should not be more
      than 10-20%. This goal has been achieved in this study with the techniques
      presented.

PMID- 22581048
TI  - [Individualization of IOL constants for two hydrophobic intraocular lenses. SRK
      II, SRK/T, Hoffer-Q, Holladay 1 and Haigis formula].
AB  - AIM: The aim of the study was an assessment of refraction error after
      implantation of two types of hydrophobic acrylic intraocular lenses and
      derivation of customized IOL constants for the SRK II, SRK/T, Hoffer Q, Holladay
      1 and Haigis formula. PURPOSE: The purpose of the present study was to analyze
      the refractive outcome of two hydrophobic acrylic intraocular lenses and to
      present a computerized calculation scheme for customization of lens-specific
      parameters provided by the lens manufacturers based on the refractive results of
      a surgeon or study center. METHODS: In this prospective monocentric study 100
      consecutive cataract eyes were treated at the Eye Hospital of the Barmherzige
      Bruder (Compassionate Brothers) in Linz/Austria with a hydrophobic acrylic
      aspherical intraocular lens (Polytech Y10AS, n = 50) or a hydrophobic acrylic
      spherical intraocular lens (Hoya PC-60R, n = 50). The biometrical data were
      assessed preoperatively together with the refractive outcome 8-10 weeks after
      treatment in order to analyze the deviation of postoperative refraction
      (spherical equivalent) from target refraction (DeltaREF) and to customize the
      lens constants for the SRK II, SRK/T, Hoffer Q, Holladay 1 and Haigis formula.
      RESULTS: Based on this data set it could be demonstrated that using the lens
      constant provided by the manufacturer (DeltaREF) the Polytech lens showed a
      systematic trend to myopia in contrast to the Hoya lens which ranged around zero.
      This trend could be compensated by selecting appropriate lens specific constants.
      For the Polytech/Hoya lens median lens constants of: A = 118.0/118.6 (SRK II), A
      = 117.9/118.6 (SRK/T), pACD = 4.8/5.1 (Hoffer Q), SF = 1.1/1.5 (Holladay I) and d
      = 4.2/4.6 (Haigis) were extracted and using linear regression a lens constant
      triplet for the Haigis formula of a(0) = 4.39, a(1) = 0.29, a(2) = 0.11/a0 =
      4.73, a(1) = 0.30, a(2) = -0.01 could be derived. CONCLUSIONS: Ophthalmic
      surgeons or surgical centers are encouraged to check (refractive) outcomes after
      cataract surgery permanently in terms of quality control. If a systematic trend
      in DeltaREF could be extracted from the data set a customization of the lens
      specific constants is recommended to eliminate systematic errors. Such
      customization is only valid for a dedicated environment (e.g. for one surgical
      center with standardized surgical techniques and measurement equipment) and
      cannot be generalized.

PMID- 22581049
TI  - [Access to healthcare services for elderly patients with neovascular age-related
      macular degeneration].
AB  - BACKGROUND: Neovascular (nv) age-related macular degeneration (AMD) is the
      leading cause of blindness in Germany and is usually treated with monthly
      injections of anti-VEGF agents. The current level and the estimated need of
      service provision for nv-AMD were assessed. METHODS: Current levels of service
      provision with ranibizumab (Lucentis) were documented in 3,633 patients in the
      WAVE study, the currently largest observational study in Germany on the use of
      anti-VEGF agents. The expected need was calculated using German population
      figures for 2010 and available prevalence data. Both were stratified by age and
      gender and descriptively analyzed. RESULTS: A larger number of younger patients
      with nv-AMD (< 75 years) than expected were treated in the WAVE study. Expected
      need in the age groups 75-84 years and 84 years and older was much higher than
      the proportion of patients actually treated in these age groups (up to 3 times).
      Based on expected need, women accessed treatment less often than men. CONCLUSION:
      In the WAVE study, less elderly persons and in particular elderly women seemed to
      access treatment for nv-AMD than expected. Future studies should investigate
      barriers in accessing treatment for nv-AMD and how to address these problems.

PMID- 22581050
TI  - [A 2-year-old patient with acute proptosis].
AB  - Hemorrhage into an orbital lymphangioma can cause acute proptosis. A lymphangioma
      must be distinguished from acute threatening causes of rapidly developing
      proptosis in childhood, such as orbital cellulitis or malignant tumors
      (rhabdomyosarcoma). Imaging (magnetic resonance imaging, ultrasound, computed
      tomography) and histopathological evaluation are required for the final
      diagnosis. Immunohistochemical staining of lymphatic vessels with podoplanin can
      be useful for confirmation of the diagnosis.

PMID- 22581051
TI  - [Retinitis pigmentosa - a review. Pathogenesis, guidelines for diagnostics and
      perspectives].
AB  - Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of
      hereditary retinal disorders, being one of the most common types of retinal
      degeneration with a prevalence of 1:4,000. More than 45 genes have so far been
      associated with RP and defects cause a progressive loss of rod photoreceptor
      function, followed by cone photoreceptor dysfunction often leading to complete
      blindness. Enormous progress has been made in research in recent years and the
      new therapeutic approaches are promising. Furthermore, with the help of improved
      molecular genetic and functional diagnostic tools an early recognition and
      differentiation has become possible. However, at present no established therapy
      is available, therefore, social and professional consequences are essential tasks
      to deal with. This paper summarizes the basic principles of retinal
      pathophysiology, clinical findings, diagnostics and therapeutic perspectives,
      furthermore, the implications for general ophthalmologists are provided.

PMID- 22581052
TI  - High-throughput biophysical measurement of human red blood cells.
AB  - This paper reports a microfluidic system for biophysical characterization of red
      blood cells (RBCs) at a speed of 100-150 cells s(-1). Electrical impedance
      measurement is made when single RBCs flow through a constriction channel that is
      marginally smaller than RBCs' diameters. The multiple parameters quantified as
      mechanical and electrical signatures of each RBC include transit time, impedance
      amplitude ratio, and impedance phase increase. Histograms, compiled from 84,073
      adult RBCs (from 5 adult blood samples) and 82,253 neonatal RBCs (from 5 newborn
      blood samples), reveal different biophysical properties across samples and
      between the adult and neonatal RBC populations. In comparison with previously
      reported microfluidic devices for single RBC biophysical measurement, this system
      has a higher throughput, higher signal to noise ratio, and the capability of
      performing multi-parameter measurements.

PMID- 22581053
TI  - Disparidad en Salud: Un Fenomeno Multidimensional.
AB  - La Disparidad en Salud (DS) ha llamado la atencion publica desde el siglo pasado,
      ha sido analizada desde diversas perspectivas y enfoques incluso variados
      terminos han sido utilizados como sinonimos pudiendo llevar a confusion e
      inequidades al momento de su operacionalizacion. Sin embargo es importante
      senalar que las publicaciones coinciden en que la DS es uno de las determinantes
      esenciales a considerar al momento de definir pollticas publicas. El proposito de
      esta publicacion es analizar la disparidad en salud incorporando; a) los aspectos
      claves de su conceptualizacion, b) la evolucion historica del concepto, c) las
      estrategias que se han generado para enfrentarla, d) los factores considerados
      determinantes, y e) los aspectos eticos y la contribucion de la investigacion en
      la disminucion de la DS.Health Disparities (HD) have been at the center of public
      attention for the past century. They have been analyzed from diverse perspectives
      utilizing various terms as synonyms that can lead to confusion and inequality at
      the moment of operationalization. Despite this, it is important to indicate that
      publications agree that HD are essential determinants that must be considered in
      the definition of public policy. The objective of this publication is to analyze
      health disparities incorporating; (a) key aspects in their conceptualization, (b)
      the historic evolution of the concept, (c) strategies that have been generated to
      confront them, (d) determining factors, and (e) ethical aspects and the
      contribution of research in decreasing HD.

PMID- 22581054
TI  - MYC suppresses cancer metastasis by direct transcriptional silencing of alphav
      and beta3 integrin subunits.
AB  - Overexpression of MYC transforms cells in culture, elicits malignant tumours in
      experimental animals and is found in many human tumours. We now report the
      paradoxical finding that this powerful oncogene can also act as a suppressor of
      cell motility, invasiveness and metastasis. Overexpression of MYC stimulated
      proliferation of breast cancer cells both in culture and in vivo as expected, but
      inhibited motility and invasiveness in culture, and lung and liver metastases in
      xenografted tumours. We show further that MYC represses transcription of both
      subunits of alphavbeta3 integrin, and that exogenous expression of beta3 integrin
      in human breast cancer cells that do not express this integrin rescues
      invasiveness and migration when MYC is downregulated. These data uncover an
      unexpected function of MYC, provide an explanation for the hitherto puzzling
      literature on the relationship between MYC and metastasis, and reveal a variable
      that could influence the development of therapies that target MYC.

PMID- 22581056
TI  - Tumoral epithelial and stromal expression of SMAD proteins in pancreatic ductal
      adenocarcinomas.
AB  - BACKGROUND: SMAD proteins, intracellular mediators of the transforming growth
      factor (TGF)-beta pathway, function within two axes, the SMAD1/5/8 and SMAD2/3,
      connected to TGF-beta and bone morphogenetic protein (BMP) ligands. The SMAD
      proteins of these two axes dimerize with SMAD4 and translocate to the nucleus.
      SMAD signaling is characterized by a dichotomic functioning, with tumor
      suppressive functions and with loss of normal growth inhibitory responses,
      depending on the carcinogenesis stage. SMAD proteins also have pro-tumor effects
      including abnormal extracellular matrix production. Among tumors, pancreatic
      cancers harbor SMAD4 inactivation the most frequently and the SMAD proteins are
      considered to be key factors in pancreatic carcinogenesis. METHODS: Our aims were
      to study the expression patterns of the different types of SMAD proteins in
      pancreatic ductal adenocarcinomas treated by surgical resection (without
      neoadjuvant treatment) and their correlations with morphological and clinical
      characteristics. We examined the immunohistochemical expression of SMAD4,
      SMAD1/5/8, and SMAD2/3 in 99 pancreatic ductal adenocarcinomas. Antibodies
      directed against the activated, phosphorylated forms of proteins were used when
      appropriate (SMAD1/5/8, SMAD2/3). Protein expression in the epithelial tumor
      cells and in stromal fibroblasts was analyzed with regard to morphological and
      clinical data. RESULTS: Epithelial tumor cells showed SMAD1/5/8, SMAD2/3, and,
      SMAD4 expression in 13, 93, and 45 tumors, respectively, and stromal fibroblast
      expression in 5, 11, and 22 tumors, respectively. Epithelial SMAD4 was associated
      with a low, T1 or T2, TNM stage, and with the presence of an abundant stroma (p =
      0.05 and <0.01, respectively). Activated stromal fibroblast SMAD2/3 expression
      was correlated with the presence of a fibrotic focus (p = 0.01), whereas
      fibroblast SMAD4 was related to a tendency for shorter postsurgical overall
      survival (p = 0.07). The relationship of stromal, fibroblast SMAD4 to a worse
      outcome attained statistical significance in the group of patients with T1 and
      with N1 stage tumors (p < 0.01 and p = 0.04, respectively). CONCLUSION: In
      pancreatic ductal adenocarcinomas, SMAD protein expression in epithelial tumor
      cells or in stromal fibroblasts was related to stromal features and to a shorter
      postsurgical overall survival. Our results point out that the SMAD proteins play
      a role in the microenvironment of this highly fibrotic tumor type.

PMID- 22581055
TI  - Recruitment of the human Cdt1 replication licensing protein by the loop domain of
      Hec1 is required for stable kinetochore-microtubule attachment.
AB  - Cdt1, a protein critical for replication origin licensing in G1 phase, is
      degraded during S phase but re-accumulates in G2 phase. We now demonstrate that
      human Cdt1 has a separable essential mitotic function. Cdt1 localizes to
      kinetochores during mitosis through interaction with the Hec1 component of the
      Ndc80 complex. G2-specific depletion of Cdt1 arrests cells in late prometaphase
      owing to abnormally unstable kinetochore-microtubule (kMT) attachments and Mad1
      dependent spindle-assembly-checkpoint activity. Cdt1 binds a unique loop
      extending from the rod domain of Hec1 that we show is also required for kMT
      attachment. Mutation of the loop domain prevents Cdt1 kinetochore localization
      and arrests cells in prometaphase. Super-resolution fluorescence microscopy
      indicates that Cdt1 binding to the Hec1 loop domain promotes a microtubule
      dependent conformational change in the Ndc80 complex in vivo. These results
      support the conclusion that Cdt1 binding to Hec1 is essential for an extended
      Ndc80 configuration and stable kMT attachment.

PMID- 22581057
TI  - Endoscopic biliary drainage for children with persistent or exacerbated symptoms
      of choledochal cysts.
AB  - BACKGROUND: Symptoms of choledochal cysts sometimes persist or become
      exacerbated. As preoperative management for patients with these cysts, we
      prospectively employed endoscopic drainage, based on the theory that protein
      plugs cause symptoms by obstructing the pancreatobiliary ducts. METHODS: Children
      with choledochal cysts underwent endoscopic retrograde cholangiopancreatography
      (ERCP). When ERCP showed compaction with filling defects in patients with
      persistent or worsening symptoms (study patients), the placement of a short
      biliary stent tube was attempted for drainage. The clinical and ERCP findings of
      the study patients were compared with those of patients who were asymptomatic at
      ERCP (asymptomatic patients). RESULTS: There were 13 study patients (median age
      2.9 years) and 41 asymptomatic patients (4.7 years) enrolled in the study between
      August 2005 and February 2011. Study patients more frequently had jaundice and
      elevated transaminase levels. ERCP showed that all study patients had obstruction
      or compacted filling defects in the common channel or the narrow segment distal
      to the cyst. Insertion of a stent tube was successful in 11 patients. Symptoms
      were relieved soon after biliary drainage. Surgery revealed that the obstructing
      materials were protein plugs, except in one case, which involved fatty acid
      calcium stones. CONCLUSIONS: These results support the protein plug theory.
      Endoscopic short-tube stenting is adequate and effective as preoperative
      management.

PMID- 22581058
TI  - Combined effects of EGFR and Hedgehog signaling pathway inhibition on the
      proliferation and apoptosis of pancreatic cancer cells.
AB  - In the present study, we established a new experimental model to investigate the
      effects of EGFR targeting by RNAi, and the synergistic actions between the
      hedgehog (Hh) and EGFR signaling pathways on the proliferation and apoptosis in
      pancreatic cancer cells. Three human pancreatic cancer cell lines expressing EGFR
      shRNA were established, and gene expression inhibition was assessed in these
      lines using RT-PCR and western blot analysis. The effects of EGFR RNAi and Hh
      inhibition on cell proliferation and apoptosis were explored in vitro and in
      vivo. We observed that EGFR RNAi notably inhibited cell proliferation and colony
      formation, induced apoptosis and markedly decreased xenograft tumor growth.
      Furthermore, EGFR RNAi significantly enhanced cyclopamine sensitivity both in
      vitro and in vivo, and a synergistic decrease of both AKT and ERK phosphorylation
      was observed. The present study demonstrates that combined inhibition of both
      EGFR and Hh signaling pathways could establish a more promising antitumor
      approach than inhibiting each singly, and that there is a possible synergistic
      effect for Hh and EGFR signaling pathways on ERK and AKT phosphorylation.

PMID- 22581059
TI  - Fully relativistic rovibrational energies and spectroscopic constants of the
      lowest X:(1)0(+)g, A':(1)2( u ), A:(1)1 ( u ), B':(1)0(-)u and B:(1)0(+)u states
      of molecular chlorine.
AB  - The main goal of this paper is to present the rovibrational energies and
      spectroscopic constants of the Cl(2) molecular system in the relativistic states
      [Formula: see text], A':(1)2( u ), A:(1)1( u ), [Formula: see text] and [Formula:
      see text]. More precisely, we have evaluated the Cl(2) omega ( e ), omega ( e ) x
      ( e ), omega ( e ) y ( e ), alpha ( e ), gamma ( e ) and B ( e ) rovibrational
      spectroscopic constants using two different procedures. The first was obtained by
      combining the rovibrational energies, calculated through solving Schrodinger's
      nuclear equation and the diatomic rovibrational energy equation. The second was
      obtained by using the Dunham method. The calculated properties are in good
      agreement with available experimental data.

PMID- 22581060
TI  - Solvent effect on cation-pi interactions with Al3+.
AB  - Cation-pi interactions are known to be one of the strongest noncovalent forces in
      the gas phase, but they rarely occur in a fully solvated environment. The present
      work used two different ab initio molecular dynamics-based approaches to describe
      the correlation between the strength of the cation-pi interactions and the number
      of water molecules surrounding the cation. Five different complexes between an
      aluminum cation and different molecules containing aromatic rings were studied,
      and the degree of hydration of each complex was varied. Results indicated that
      cation-pi interactions vanish when the aluminum cation is surrounded by more than
      three water molecules. The results also highlighted the influence of -OH ligands
      on the interaction strength.

PMID- 22581061
TI  - Mechanical stretch down-regulates expression of the Smad6 gene in cultured rat
      mesangial cells.
AB  - BACKGROUND: Glomerular hypertension aggravates glomerular sclerosis by inducing
      growth factors, e.g., transforming growth factor-beta (TGF-beta) to mesangial
      matrix expansion. Smads are intracellular proteins that transmit signals from TGF
      beta to nucleus, and Smads are also negatively regulated by inhibitory Smads (I
      Smads), Smad6 and Smad7. However, little is known about the role of I-Smads in
      glomerular hypertension. We studied I-Smad expression in cultured mesangial cells
      subjected to mechanical stretch as an in vitro model of glomerular hypertension.
      METHODS: Rat mesangial cells were cultured under cyclic mechanical stretch
      conditions using the Flexercell Strain Unit. Phosphorylated Smad1 and Smad2 were
      determined by Western blots. The expression of Smad6 and Smad7 mRNAs was
      determined by Northern blots. Stretch-mediated I-Smad mRNAs of cells pre-treated
      with MAPK-ERK kinase inhibitor, U0126, were also determined. Localization of
      phospho-Smad1, Smad6 and Smad7 proteins in the glomerulus of Dahl salt-sensitive
      rats was determined by immunohistochemistry. RESULTS: Stretch stress increased
      phospho-Smad1 levels, and significantly decreased Smad6 mRNA to 32 % of control,
      and increased Smad7 mRNA to 136 % of control. U0126 significantly attenuated
      stretch-mediated decreases in Smad6 mRNA, but had no effect on stretch-mediated
      increases in Smad7 mRNA. Phospho-Smad1, Smad6 and Smad7 proteins were localized
      in podocytes and mesangial cells of Dahl rats. CONCLUSION: Mechanical stretch
      increases phospho-Smad1 levels and down-regulates Smad6 mRNA expression in
      mesangial cells. Stretch-mediated down-regulation of Smad6 is partially involved
      in ERK1/2 activation. These results indicate that glomerular hypertension might
      augment Smad1 signaling with concomitant attenuation of Smad6-mediated negative
      feedback.

PMID- 22581062
TI  - Development of lymphatic vasculature and morphological characterization in rat
      kidney.
AB  - BACKGROUND: The mechanisms and morphological characteristics of lymphatic
      vascular development in embryonic kidneys remain uncertain. METHODS: We examined
      the distribution and characteristics of lymphatic vessels in developing rat
      kidneys using immunostaining for podoplanin, prox-1, Ki-67, type IV collagen
      (basement membrane: BM), and alpha-smooth muscle actin (alphaSMA: pericytes or
      mural cells). We also examined the expression of VEGF-C. RESULTS: At embryonic
      day 17 (E17), podoplanin-positive lymphatic vessels were observed mainly in the
      kidney hilus. At E20, lymphatic vessels extended further into the developing
      kidneys along the interlobar vasculature. In 1-day-old pups (P1) to P20,
      lymphatic vessels appeared around the arcuate arteries and veins of the kidneys,
      with some reaching the developing cortex via interlobular vessels. In 8-week-old
      adult rats, lymphatic vessels were extensively distributed around the blood
      vasculature from the renal hilus to cortex. Only lymphatic capillaries lacking
      continuous BM and alphaSMA-positive cells were present within adult kidneys, with
      none observed in renal medulla. VEGF-C was upregulated in the developing kidneys
      and expressed mainly in tubules. Importantly, the developing lymphatic vessels
      were characterized by endothelial cells immunopositive for podoplanin, prox-1,
      and Ki-67, with no surrounding BM or alphaSMA-positive cells. CONCLUSION: During
      nephrogenesis, lymphatic vessels extend from the renal hilus into the renal
      cortex along the renal blood vasculature. Podoplanin, prox-1, Ki-67, type IV
      collagen, and alphaSMA immunostaining can detect lymphatic vessels during
      lymphangiogenesis.

PMID- 22581063
TI  - Morning blood pressure is useful for detection of left ventricular hypertrophy in
      hemodialysis patients.
AB  - BACKGROUND: When diagnosing hypertension (HT) it is essential to determine not
      only the level of raised blood pressure (BP), but also how the condition relates
      to organ damage. The best time to measure BP for diagnosing HT in patients on
      hemodialysis (HD) remains unclear. METHODS: A total of 100 HD patients (mean age
      63.8 years, 60 males) were studied. Left ventricular hypertrophy (LVH) was
      detected by echocardiography and BP monitored for 1 week at 20 different times in
      the morning and night, before and after dialysis. We also checked for masked HT,
      i.e., patients with weekly morning HT, but not pre-dialysis HT. RESULTS: Average
      BP for the week was 141.9 +/-19.0/79.6 +/- 10.6 mmHg, with 68 patients classified
      as hypertensive. Average morning BP was 144.6 +/- 19.8/81.7 +/- 11.3 mmHg, and 71
      patients had weekly morning HT. In addition, 62 patients had LVH and 51 patients
      had relative morning HT. Multiple logistic analyses showed that LVH was
      associated with weekly morning HT, morning HT on HD and non-HD days, average HT,
      and relative morning HT. However, evening, pre-dialysis, and post-dialysis HT
      showed no association with LVH. Masked HT was found in 20 % of patients. If HT
      had been diagnosed using only pre-dialysis BP, 20 of the 71 patients with weekly
      morning HT would not have been detected. CONCLUSION: Morning BP is useful for
      detecting LVH in HD patients. Monitoring of morning BP may be superior to
      measurements taken at other times for diagnosing HT.

PMID- 22581065
TI  - Characterization of an organic solvent-tolerant alpha-amylase from a halophilic
      isolate, Thalassobacillus sp. LY18.
AB  - A halophilic isolate Thalassobacillus sp. LY18 producing extracellular amylase
      was isolated from the saline soil of Yuncheng Salt Lake, China. Production of the
      enzyme was synchronized with bacterial growth and reached a maximum level during
      the early stationary phase. The amylase was purified to homogeneity with a
      molecular mass of 31 kDa. Major products of soluble starch hydrolysis were
      maltose and maltotriose, indicating an alpha-amylase activity. Optimal enzyme
      activity was found to be at 70 degrees C, pH 9.0, and 10 % NaCl. The alpha
      amylase was highly stable over broad temperature (30-90 degrees C), pH (6.0
      12.0), and NaCl concentration (0-20 %) ranges, showing excellent thermostable,
      alkalistable, and halotolerant nature. The enzyme was stimulated by Ca(2+), but
      greatly inhibited by EDTA, indicating it was a metalloenzyme. Complete inhibition
      by diethyl pyrocarbonate and beta-mercaptoethanol revealed that histidine residue
      and disulfide bond were essential for enzyme catalysis. The surfactants tested
      had no significant effects on the amylase activity. Furthermore, it showed high
      activity and stability in the presence of water-insoluble organic solvents with
      log P (ow) >= 2.13.

PMID- 22581064
TI  - Effects of sevelamer hydrochloride on mortality, lipid abnormality and arterial
      stiffness in hemodialyzed patients: a propensity-matched observational study.
AB  - BACKGROUND: Cause-and-effect associations between sevelamer hydrochloride (HCl)
      and mortality have yet to be clarified. The effects of sevelamer HCl on
      mortality, lipid abnormality and arterial stiffness were examined in patients
      with chronic kidney disease stage 5D. METHODS: The effects of sevelamer HCl were
      studied by a single-center cohort study that was conducted from January 1, 2005
      to December 31, 2008 (n = 483). By the end of the study, 172 patients (Sevelamer
      group) had succeeded in continuing sevelamer HCl for >6 months (median 37
      months), and 300 patients (Control group) had received calcium carbonate (n =
      264) or no phosphate binder (n = 36). The mortality and other outcomes were
      compared between these two groups after matching by a propensity score calculated
      using age, gender, diabetes prevalence, and dialysis vintage. RESULTS: All-cause
      [hazard ratio (HR) 0.4, P = 0.02] and cardiovascular (CV)-cause [HR 0.29, P =
      0.03] cumulative mortality were significantly lower in the matched Sevelamer
      group than in the matched Control group. The matched Sevelamer group showed
      increased high-density lipoprotein cholesterol (P = 0.003) and no change in pulse
      wave velocity (PWV) and ankle-brachial index (ABI), whereas the matched Control
      group showed increased serum low-density lipoprotein (LDL) cholesterol (P =
      0.003), increased PWV (P = 0.03), and decreased ABI (P = 0.0009). Change in serum
      LDL cholesterol level correlated inversely with sevelamer HCl dosage (P = 0.02).
      CONCLUSIONS: Reduced mortality in patients with sevelamer HCl may, at least in
      part, be explained by an improvement in dyslipidemia and arterial stiffness by
      sevelamer HCl.

PMID- 22581066
TI  - Development of a bioprocess to convert PET derived terephthalic acid and
      biodiesel derived glycerol to medium chain length polyhydroxyalkanoate.
AB  - Sodium terephthalate (TA) produced from a PET pyrolysis product and waste
      glycerol (WG) from biodiesel manufacture were supplied to Pseudomonas putida GO16
      in a fed-batch bioreactor. Six feeding strategies were employed by altering the
      sequence of TA and WG feeding. P. putida GO16 reached 8.70 g/l cell dry weight
      (CDW) and 2.61 g/l PHA in 48 h when grown on TA alone. When TA and WG were
      supplied in combination, biomass productivity (g/l/h) was increased between 1.3-
      and 1.7-fold and PHA productivity (g/l/h) was increased 1.8- to 2.2-fold compared
      to TA supplied alone. The monomer composition of the PHA accumulated from TA or
      WG was predominantly composed of 3-hydroxydecanoic acid. PHA monomers 3
      hydroxytetradeeanoic acid and 3-hydroxytetradecenoic acid were not present in PHA
      accumulated from TA alone but were present when WG was supplied to the
      fermentation. When WG was either the sole carbon source or the predominant carbon
      source supplied to the fermentation the molecular weight of PHA accumulated was
      lower compared to PHA accumulated when TA was supplied as the sole substrate.
      Despite similarities in data for the properties of the polymers, PHAs produced
      with WG present in the PHA accumulation phase were tacky while PHA produced where
      TA was the sole carbon substrate in the polymer accumulation phase exhibited
      little or no tackiness at room temperature. The co-feeding of WG to fermentations
      allows for increased utilisation of TA. The order of feeding of WG and TA has an
      effect on TA utilisation and polymer properties.

PMID- 22581067
TI  - Novel whole-cell biocatalysts with recombinant hydroxysteroid dehydrogenases for
      the asymmetric reduction of dehydrocholic acid.
AB  - Ursodeoxycholic acid is an important pharmaceutical so far chemically synthesized
      from cholic acid. Various biocatalytic alternatives have already been discussed
      with hydroxysteroid dehydrogenases (HSDH) playing a crucial role. Several whole
      cell biocatalysts based on a 7alpha-HSDH-knockout strain of Escherichia coli
      overexpressing a recently identified 7beta-HSDH from Collinsella aerofaciens and
      a NAD(P)-bispecific formate dehydrogenase mutant from Mycobacterium vaccae for
      internal cofactor regeneration were designed and characterized. A strong pH
      dependence of the whole-cell bioreduction of dehydrocholic acid to 3,12-diketo
      ursodeoxycholic acid was observed with the selected recombinant E. coli strain.
      In the optimal, slightly acidic pH range dehydrocholic acid is partly undissolved
      and forms a suspension in the aqueous solution. The batch process was optimized
      making use of a second-order polynomial to estimate conversion as function of
      initial pH, initial dehydrocholic acid concentration, and initial formate
      concentration. Complete conversion of 72 mM dehydrocholic acid was thus made
      possible at pH 6.4 in a whole-cell batch process within a process time of 1 h
      without cofactor addition. Finally, a NADH-dependent 3alpha-HSDH from Comamonas
      testosteroni was expressed additionally in the E. coli production strain
      overexpressing the 7beta-HSDH and the NAD(P)-bispecific formate dehydrogenase
      mutant. It was shown that this novel whole-cell biocatalyst was able to convert
      50 mM dehydrocholic acid directly to 12-keto-ursodeoxycholic acid with the
      formation of only small amounts of intermediate products. This approach may be an
      efficient process alternative which avoids the costly chemical epimerization at C
      7 in the production of ursodeoxycholic acid.

PMID- 22581068
TI  - Membrane interaction and antibacterial properties of chensinin-1, an
      antimicrobial peptide with atypical structural features from the skin of Rana
      chensinensis.
AB  - Many antimicrobial peptides from amphibian skin have been purified and
      structurally characterized and may be developed as therapeutic agents. Here we
      describe the antibacterial properties and membrane interaction of chensinin-1, a
      cationic arginine/histidine-rich antimicrobial peptide, from the skin secretions
      of Rana chensinensis. The amino acid composition, sequence, and atypical
      structure of chensinin-1 differ from other known antimicrobial peptides from
      amphibian skin. Chensinin-1 exhibited selective antimicrobial activity against
      Gram-positive bacteria, was inactive against Gram-negative bacteria, and had no
      hemolytic activity on human erythrocytes. The CD spectra for chensinin-1
      indicated that the peptide adopted an aperiodic structure in water and a
      conformational structure with 20 % beta-strands, 8 % alpha-helices, and the
      remaining majority of random coils in the trifluoroethanol or SDS solutions. Time
      kill kinetics against Gram-positive Bacillus cereus demonstrated that chensinin-1
      was rapidly bactericidal at 2* MIC and PAE was found to be >5 h. Chensinin-1
      caused rapid and large dye leakage from negatively charged model vesicles.
      Furthermore, membrane permeation assays on intact B. cereus indicated that
      chensinin-1 induced membrane depolarization in less than 1 min and followed to
      damage the integrity of the cytoplasmic membrane and resulted in efflux of
      molecules from cytoplasma. Hence, the primary target of chensinin-1 action was
      the cytoplasmic membrane of bacteria. Chensinin-1 was unable to overcome
      bacterial resistance imposed by the lipopolysaccharide leaflet, the major
      constituent of the outer membrane of Gram-negative bacteria. Lipopolysaccharide
      induced oligomerization of chensinin-1, thus preventing its translocation across
      the outer membrane.

PMID- 22581069
TI  - Maximally localized Wannier functions in LaMnO3 within PBE + U, hybrid
      functionals and partially self-consistent GW: an efficient route to construct ab
      initio tight-binding parameters for eg perovskites.
AB  - Using the newly developed VASP2WANNIER90 interface we have constructed maximally
      localized Wannier functions (MLWFs) for the e(g) states of the prototypical Jahn
      Teller magnetic perovskite LaMnO(3) at different levels of approximation for the
      exchange-correlation kernel. These include conventional density functional theory
      (DFT) with and without the additional on-site Hubbard U term, hybrid DFT and
      partially self-consistent GW. By suitably mapping the MLWFs onto an effective
      e(g) tight-binding (TB) Hamiltonian we have computed a complete set of TB
      parameters which should serve as guidance for more elaborate treatments of
      correlation effects in effective Hamiltonian-based approaches. The method
      dependent changes of the calculated TB parameters and their interplay with the
      electron-electron (el-el) interaction term are discussed and interpreted. We
      discuss two alternative model parameterizations: one in which the effects of the
      el-el interaction are implicitly incorporated in the otherwise 'noninteracting'
      TB parameters and a second where we include an explicit mean-field el-el
      interaction term in the TB Hamiltonian. Both models yield a set of tabulated TB
      parameters which provide the band dispersion in excellent agreement with the
      underlying ab initio and MLWF bands.

PMID- 22581070
TI  - Combined cognitive remediation and functional skills training for schizophrenia:
      effects on cognition, functional competence, and real-world behavior.
AB  - OBJECTIVE: Cognitive remediation is an efficacious treatment for schizophrenia
      and, when used within broader psychosocial treatments, improves transfer to real
      world behavior change. The authors examined whether cognitive remediation
      effectively generalizes to functional competence and real-world functioning as a
      standalone treatment and when combined with a functional skills treatment.
      METHOD: Outpatients with schizophrenia (N=107) were randomly assigned to receive
      cognitive remediation, functional adaptation skills training, or combined
      treatment, with cognitive remediation preceding functional skills training.
      Clinical symptoms, neurocognition, social competence, functional competence, and
      case-manager-rated real-world behavior were assessed at baseline, at end of
      treatment, and at a 12-week durability assessment. RESULTS: Neurocognition
      improved, with durable effects, after cognitive remediation but not after
      functional skills training. Social competence improved both with functional
      skills training and with combined treatment but not with cognitive remediation
      alone. Improvements in functional competence were greater and more durable with
      combined treatment. Cognitive remediation alone did not produce significant
      improvements in real-world behavior, but when combined with functional skills
      training, statistically significant improvements from baseline to end of
      treatment and follow-up were observed in community or household activities and
      work skills. Number-needed-to-treat analyses suggest that as few as three cases
      are required for treatment to induce a meaningful improvement in functional
      skills. CONCLUSIONS: In a short intervention, cognitive remediation produced
      robust improvements in neurocognition. Generalization to functional competence
      and real-world behavior was more likely when supplemental skills training and
      cognitive remediation were combined.

PMID- 22581071
TI  - Impacts of ocean acidification on respiratory gas exchange and acid-base balance
      in a marine teleost, Opsanus beta.
AB  - The oceanic carbonate system is changing rapidly due to rising atmospheric CO(2),
      with current levels expected to rise to between 750 and 1,000 MUatm by 2100, and
      over 1,900 MUatm by year 2300. The effects of elevated CO(2) on marine calcifying
      organisms have been extensively studied; however, effects of imminent CO(2)
      levels on teleost acid-base and respiratory physiology have yet to be examined.
      Examination of these physiological processes, using a paired experimental design,
      showed that 24 h exposure to 1,000 and 1,900 MUatm CO(2) resulted in a
      characteristic compensated respiratory acidosis response in the gulf toadfish
      (Opsanus beta). Time course experiments showed the onset of acidosis occurred
      after 15 min of exposure to 1,900 and 1,000 MUatm CO(2), with full compensation
      by 2 and 4 h, respectively. 1,900-MUatm exposure also resulted in significantly
      increased intracellular white muscle pH after 24 h. No effect of 1,900 MUatm was
      observed on branchial acid flux; however, exposure to hypercapnia and HCO(3)(-)
      free seawater compromised compensation. This suggests branchial HCO(3)(-) uptake
      rather than acid extrusion is part of the compensatory response to low-level
      hypercapnia. Exposure to 1,900 MUatm resulted in downregulation in branchial
      carbonic anhydrase and slc4a2 expression, as well as decreased Na(+)/K(+) ATPase
      activity after 24 h of exposure. Infusion of bovine carbonic anhydrase had no
      effect on blood acid-base status during 1,900 MUatm exposures, but eliminated the
      respiratory impacts of 1,000 MUatm CO(2). The results of the current study
      clearly show that predicted near-future CO(2) levels impact respiratory gas
      transport and acid-base balance. While the full physiological impacts of
      increased blood HCO(3)(-) are not known, it seems likely that chronically
      elevated blood HCO(3)(-) levels could compromise several physiological systems
      and furthermore may explain recent reports of increased otolith growth during
      exposure to elevated CO(2).

PMID- 22581072
TI  - Temperature-dependent toxicity in mammals with implications for herbivores: a
      review.
AB  - Diet selection in mammalian herbivores is thought to be primarily governed by
      intrinsic properties of food, such as nutrient and plant secondary compound (PSC)
      contents, and less so by environmental factors. However, several independent
      lines of evidence suggest that the toxicity of PSCs is mediated, in part, by
      ambient temperature and that the effect of small changes in ambient temperature
      is on par with several fold changes in PSC concentration. This review describes
      the disparate lines of evidence for temperature-dependent toxicity and the
      putative mechanisms causing this phenomenon. A model is described that integrates
      thermal physiology with temperature-dependent toxicity to predict maximal dietary
      intake of plant secondary compounds by mammalian herbivores. The role of
      temperature-dependent toxicity is considered with respect to the observed changes
      in herbivorous species attributed to climate change. Possible future
      investigations and the effects of temperature-dependent toxicity on other
      endotherms are presented. Temperature-dependent toxicity has the potential to
      apply to all endotherms that consume toxins. The effects of temperature-dependent
      toxicity will likely be exacerbated with increasing ambient temperatures caused
      by climate change.

PMID- 22581073
TI  - Reduced global longitudinal and radial strain with normal left ventricular
      ejection fraction late after effective repair of aortic coarctation: a CMR
      feature tracking study.
AB  - We sought to determine whether global and regional left ventricular (LV) strain
      parameters were altered in repaired coarctation of the aorta (COA) with normal LV
      ejection fraction (EF) when compared with healthy adult controls, and whether
      such alterations were related to LV hypertrophy (LVH). We identified 81 patients
      after COA repair (31 female, age 25 +/- 8.5 years) with inclusion criteria at
      follow-up CMR of: age >=13 years, time post-repair >=10 years, no aortic valve
      disease, LV-EF >50%). LV deformation indices derived using CMR-feature tracking
      and volumetric EF were compared between COA patients and normal controls (n = 20,
      10 female, age 37 +/- 7 years), and between COA with versus without LVH. In
      repaired COA versus controls, LV-EF (%) was 62 +/- 7.2 versus 58 +/- 3.0 (p =
      0.01), and LV mass (g/m(2)) 66 +/- 16.8 versus 57.7 +/- 6.0 (p = 0.0001). LV
      global longitudinal strain (GLS) was decreased to -17.0 +/- 4.7% in COA (-20 +/-
      5% in controls, p = 0.02), and global radial strain (GRS) reduced to 40 +/- 15%
      (50 +/- 12.4% in controls, p = 0.003). The global circumferential strain (GCS)
      was preserved in COA at -23 +/- 4.7% (-24.6 +/- 2.4% in controls, p = 0.14).
      Regionally, LS decrease was marked in the basal segments (septal, p = 0.005,
      lateral, p = 0.013). In COA with LVH (n = 45, mass 76.3 +/- 12.8 g/m(2)) versus
      without LVH (n = 36, mass 52.2 +/- 10 g/m(2)), GLS was more markedly decreased (
      15.7 +/- 4.8 vs. -18.5 +/- 4.2%, p = 0.016, but GRS and GCS were similar (p =
      0.49 and 0.27). In post-repair COA with normal LV-EF, GLS and GRS are reduced
      whilst GCS is preserved. GLS reduction is more pronounced in the presence of LVH.
      GLS may qualify as indicator of early LV dysfunction.

PMID- 22581076
TI  - Evaluation of amino acid O-phosphoserine as ligand for the capture of
      immunoglubulin G from human serum.
AB  - The amino acid ortho-phosphoserine (OPS) immobilized on agarose gel was evaluated
      as a ligand for adsorption of polyclonal human immunoglobulin G (IgG) from human
      serum in the presence of low ionic strength buffers. Screening of buffer systems
      showed sodium phosphate as the buffer that exhibited higher IgG purity values.
      Through breakthrough curve analysis for agarose-OPS (feeding of 31.93 mg of total
      protein per mL of gel), a purification factor of 5.4 with an IgG purity of 89 %
      was obtained (based on IgG, IgM, IgA, HSA, and Trf nephelometric analysis). IgG
      adsorption equilibrium studies showed that these data followed the Langmuir
      Freundlich model, with cooperativity parameter (n) equal to 1.74, indicating the
      presence of positive cooperativity, probably due to multipoint interactions. The
      maximum IgG binding capacity was 24.2 mg mL(-1), near the value for the
      bioaffinity ligand protein A. The agarose-OPS adsorbent provides an attractive
      alternative for capturing of IgG from human serum.

PMID- 22581074
TI  - Impulse control disorders in Parkinson's disease: a psychosocial perspective.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disease primarily
      characterised by motor symptoms. However, another feature of PD which is
      receiving increasing attention is the phenomenon of impulse control disorders
      (ICDs), such as pathological gambling. To date, research into ICDs in PD has
      centred on a biomedical model of cause, related to the effects of dopamine
      replacement therapy. However, there are several areas of discrepancy in the
      current biomedical account of ICDs in PD. In addition, we argue that social and
      psychological factors also need to be considered to achieve a more complete
      understanding of the phenomenon. We present a novel conceptual model which
      combines biomedical and psychosocial factors in the genesis of ICDs in PD and use
      the model to identify a number of potential treatment intervention points and to
      highlight important outstanding questions concerning the inter-relationship
      between psychosocial and biomedical factors in the genesis of ICDs in PD.

PMID- 22581075
TI  - Health-related quality of life and perceived need for mental health services in
      adolescent solid organ transplant recipients.
AB  - The purpose of the current investigation was to assess interest in mental health
      services among parents of adolescent solid organ transplant recipients and the
      relationship between parent perceived need for mental health services and patient
      health-related quality of life (HRQOL). Sixty-three parents rated interest in
      receiving 10 mental health services, and patient HRQOL ratings were gathered from
      adolescent transplant recipients and their parents. Ninety-four percent of
      parents expressed some level of interest in at least one of the proposed
      services, with over 40 % indicating maximum interest. Parents' perceived need for
      mental health services was inversely related to adolescent and parent reports of
      HRQOL on the behavior, mental health, family cohesion, and parental impact
      emotional domains. Results suggest that parents of adolescent solid organ
      transplant recipients are interested in receiving mental health services for
      their families. Assessment of need for mental health services and HRQOL may
      inform the medical team of families requiring intervention.

PMID- 22581077
TI  - Network-based identification of novel connections among apoptotic signaling
      pathways in cancer.
AB  - MicroRNAs (miRNAs), highly conserved, non-coding endogenous RNA and nearly ~22
      nucleotides (nt) in length, are well-known to regulate several apoptotic pathways
      in cancer. In this study, we computationally constructed the initial human
      apoptotic PPI network by several online databases, and further integrated these
      high-throughput datasets into a Naive Bayesian model to predict protein
      functional connections. Based on the modified apoptotic network, we identified
      several apoptotic hub proteins such as TP53, SRC, M3K3/5/8, cyclin-dependent
      kinase2/6, TNFR16/19, and TGF-beta receptor 1/2. Subsequently, we identified some
      microRNAs that could target the aforementioned apoptotic hub proteins by using
      TargetScan, PicTar, and Diana-MicroH. In conclusion, these results demonstrate
      the PPI network-based identification of new connections amongst apoptotic
      pathways in cancer, which may shed new light on the intricate relationships
      between core apoptotic pathways and some targeted miRNAs in human cancers.

PMID- 22581078
TI  - Coenzyme regeneration in hexanol oxidation catalyzed by alcohol dehydrogenase.
AB  - The enzymatic ways of coenzyme regeneration include the addition of a second
      enzyme to the system or the addition of the co-substrate. In the present study,
      both methods of enzymatic coenzyme (NAD(+)) regeneration were studied and
      compared in the reaction of hexanol oxidation catalyzed by alcohol dehydrogenase
      (ADH). As a source of ADH, commercial isolated enzyme and the whole baker's yeast
      cells were used. First, coenzyme regeneration was employed in the reaction of
      acetaldehyde reduction catalyzed by the same enzyme that catalyzed the main
      reaction, and then NAD(+) regeneration was applied in the reaction of pyruvate
      reduction catalyzed by L-lactate dehydrogenase (L-LDH). Hexanal was obtained as
      the product of hexanol oxidation catalyzed by isolated ADH while hexaonic acid
      was detected as a product of the same reaction catalyzed by baker's yeast cells.
      All of the used biocatalysts were kinetically characterized. The mass reactions
      were described by the mathematical models. All models were validated in the batch
      reactor. One hundred percent hexanol conversion was obtained using permeabilized
      yeast cells using both methods of cofactor regeneration. By using isolated enzyme
      ADH, the higher conversion was achieved in a system with cofactor regeneration
      catalyzed by L-LDH.

PMID- 22581079
TI  - Manipulation of the conformation and enzymatic properties of T1 lipase by site
      directed mutagenesis of the protein core.
AB  - In silico and experimental investigations were conducted to explore the effects
      of substituting hydrophobic residues, Val, Met, Leu, Ile, Trp, and Phe into Gln
      114 of T1 lipase. The in silico investigations accurately predicted the enzymatic
      characteristics of the mutants in the experimental studies and provided
      rationalization for some of the experimental observations. Substitution with Leu
      successfully improved the conformational stability and enzymatic characteristics
      of T1 lipase. However, replacement of Gln114 with Trp negatively affected T1
      lipase and resulted in the largest disruption of protein stability, diminished
      lipase activity and inferior enzymatic characteristics. These results suggested
      that the substitution of a larger residue in a densely packed area of the protein
      core can have considerable effects on the structure and function of an enzyme.
      This is especially true when the residue is next to the catalytic serine as
      demonstrated with the Phe and Trp mutation.

PMID- 22581080
TI  - Orlistat, a novel potent antitumor agent for ovarian cancer: proteomic analysis
      of ovarian cancer cells treated with Orlistat.
AB  - Orlistat is an orally administered anti-obesity drug that has shown significant
      antitumor activity in a variety of tumor cells. To identify the proteins involved
      in its antitumor activity, we employed a proteomic approach to reveal protein
      expression changes in the human ovarian cancer cell line SKOV3, following
      Orlistat treatment. Protein expression profiles were analyzed by 2-dimensional
      polyacrylamide gel electrophoresis (2-DE) and protein identification was
      performed on a MALDI-Q-TOF MS/MS instrument. More than 110 differentially
      expressed proteins were visualized by 2-DE and Coomassie brilliant blue staining.
      Furthermore, 71 proteins differentially expressed proteins were positively
      identified via mass spectrometry (MS)/MS analysis. In particular, PKM1/2, a key
      enzyme involved in tumorigenesis, was found to be significantly downregulated in
      SKOV3 cells following treatment with Orlistat. Moreover, PKM1/2 was proved to be
      downregulated in SKOV3 cells by western blot analysis after treatment with
      Orlistat. Taken together, using proteomic tools, we identified several
      differentially expressed proteins that underwent Orlistat-induced apoptosis,
      particularly PKM2. These changes confirmed our hypothesis that Orlistat is a
      potential inhibitor of ovarian cancer and can be used as a novel adjuvant
      antitumor agent.

PMID- 22581081
TI  - Combined transcranial-orbital approach for resection of optic nerve gliomas:  a
      clinical and anatomical study.
AB  - PURPOSE: To describe a combined transcranial-orbital approach for en bloc
      resection of optic nerve gliomas with preservation of the annulus of Zinn that
      minimizes recurrence and prevents postoperative paralytic ptosis. METHODS: 
      DESIGN: A retrospective, noncomparative, interventional case series. STUDY
      POPULATION: All patients who underwent optic nerve glioma resections using this
      technique with the authors between 1994 and 2010. PROCEDURE: A transcranial
      orbital approach is used to resect the intracranial segment of the optic nerve
      glioma from 2 mm anterior to the chiasm to the posterior extent of annulus of
      Zinn. The proximal transected edge of the nerve is examined intraoperatively for
      tumor margin clearance. Through a superior orbitotomy exposure, the entire
      retrobulbar segment of the tumor is transected from the globe to the annulus of
      Zinn. A simulation of the procedure in a cadaver and en bloc resection of the
      orbital apex are performed to demonstrate the subdural plane of dissection within
      the annulus of Zinn. MAIN OUTCOME MEASURES: Postoperative outcome measures
      include: health of the ipsilateral globe, paralytic ptosis, postoperative
      complications, and tumor recurrence. RESULTS: Eleven patients underwent resection
      of optic nerve gliomas using this technique. No patients had tumor recurrence or
      developed postoperative paralytic ptosis. CONCLUSIONS: The combined transcranial
      orbital approach with preservation of the annulus of Zinn is a safe and effective
      way to remove optic nerve gliomas and ensure tumor clearance while avoiding
      paralytic ptosis.

PMID- 22581082
TI  - Postoperative application of mitomycin-C in endocanalicular laser
      dacryocystorhinostomy.
AB  - PURPOSE: To determine the safety and efficacy of the multiple postoperative
      applications of mitomycin-C (MMC) after endocanalicular laser
      dacryocystorhinostomy. METHODS: Prospective interventional case series of 125
      endocanalicular laser dacryocystorhinostomies using the diode laser. Mitomycin-C
      was placed intra-operatively in all cases. Application of MMC was also done
      postoperatively at 1 week, 2 weeks, and 3 weeks. The main outcome measure for
      success was resolution or improvement of epiphora, the patency of the osteum and
      the presence or absence of complications from the MMC application. Patients were
      followed up for at least 12 months. RESULTS: A total of 125 consecutive
      endocanalicular laser dacryocystorhinostomies on 114 patients (102 women, 12 men,
      mean age 60 years) were done from January 2002 to January 2005. The success rate
      at 12 months postoperatively was 92.8%. All failures were due to cicatricial
      closure of the osteum. No significant intra-operative and postoperative nasal
      complications from the MMC were recorded. CONCLUSION: Multiple postoperative
      applications of MMC appears to be a safe and effective adjunctive modality after
      endocanalicular laser dacryocystorhinostomy in primary acquired nasolacrimal duct
      obstruction.

PMID- 22581083
TI  - Entropion-ectropion:  the influence of axial globe length on lower eyelid
      malposition.
AB  - PURPOSE: To evaluate the effect of axial globe length and other biometry
      parameters on age-related lower eyelid malposition. METHODS: Consecutive patients
      with involutional lower eyelid malposition underwent preoperative biometry with
      Zeiss IOL Master and Hertel's exophthalmometer prior to surgery. Patients with
      other causes of eyelid malposition and thyroid eye disease were excluded.
      GraphPad InStat was used for t test and chi-square statistical analysis. RESULTS:
      Data on 57 eyelids of 52 Caucasian patients were collected. There were 28
      ectropions and 29 entropions. The mean axial globe length in the ectropion group
      (23.5 mm, standard deviation +/- 0.9) was significantly longer than in the
      entropion group (22.7 mm, standard deviation +/- 1.03) (p = 0.008). There was
      significant sex predilection, with entropion more common in women and ectropion
      more common in men (p = 0.03). The mean axial globe projection in the ectropion
      group was 16.6 mm (standard deviation +/- 2.4) and in the entropion group was
      14.6 mm (standard deviation +/- 2.7) (p = 0.002). There was no statistical
      difference in age, keratometry, amount of astigmatism, and cylinder axis.
      CONCLUSION: Involutional eyelid malposition directly correlates with axial globe
      length with the ectropion group having lengthier eyes compared with the entropion
      group. Hence, axial globe length could be an influential factor in the onset of
      involutional eyelid malposition.

PMID- 22581084
TI  - Cosmetic orbital inferomedial decompression:  quantifying the risk of diplopia
      associated with extraocular muscle dimensions.
AB  - PURPOSE: To quantify the risk of new diplopia in inferomedial orbital
      decompression performed for cosmetic reasons. METHODS: Retrospective analysis of
      114 patients with Graves orbitopathy who underwent an inferomedial orbital
      decompression. No patient had diplopia in any of the gaze positions or optic
      neuropathy. A single coronal slice 9 mm posterior to the lateral orbital rim was
      employed to quantify the muscular index of the extraocular recti and of the
      superior complex. A control group of 56 patients imaged for other reasons were
      also measured. After surgery the oculomotor status of all patients who complained
      of diplopia and of 51 patients free of diplopia was measured with the prism and
      cover test in the primary and secondary gaze positions. RESULTS: The rate of new
      onset diplopia was 14.0% (16 patients). Eye deviations were confirmed in 14
      patients. Of these, 10 had significant strabismus that warranted surgical or
      prism treatment. Most patients had esotropia associated with small vertical
      deviations. The size of the medial and inferior recti was significantly
      associated with the development of diplopia. The estimated odds for the
      appearance of diplopia in patients with muscle enlargement was 12.76 (medial
      rectus) and 5.21 (inferior rectus). Small-angle deviations were also detected in
      27.4% of patients who did not experience diplopia. CONCLUSIONS: Medial and
      inferior recti enlargement is a strong predictor of new-onset diplopia. A large
      number of patients who do not report diplopia also present with small-angle
      deviations.

PMID- 22581085
TI  - Management of radiation-induced severe anophthalmic socket contracture in
      patients with uveal melanoma.
AB  - PURPOSE: High-dose radiotherapy can cause contracture of the anophthalmic socket,
      but the incidence of this complication in patients with enucleation for uveal
      melanoma has not been reported previously. The authors reviewed the surgical
      management and outcomes in terms of successful prosthesis wear in patients with
      severe contracture of the anophthalmic socket treated with high-dose radiotherapy
      for high-risk uveal melanoma, and they estimated the relative risk of this
      complication. METHODS: The medical records of all consecutive patients enrolled
      in a prospective uveal-melanoma tissue-banking protocol at the authors'
      institution who underwent enucleation between January 2003 and December 2010 were
      reviewed. Patients who underwent adjuvant radiotherapy of the enucleated socket
      were further studied. RESULTS: Of the 68 patients enrolled in the prospective
      tissue-banking protocol, 12 had high-risk histologic features (e.g., extrascleral
      spread or vortex vein invasion) and were treated with 60 Gy of external beam
      radiotherapy after enucleation. Five of these patients (41.7%) experienced severe
      socket contracture precluding prosthesis wear. The median time to onset of
      contracture following completion of radiotherapy was 20 months. Three patients
      underwent surgery, which entailed scar tissue release, oral mucous membrane
      grafting, and socket reconstruction; 2 patients declined surgery. All 3 patients
      who had surgery experienced significant improvement of socket contracture that
      enabled patients to wear a prosthesis again. CONCLUSION: High-dose radiotherapy
      after enucleation in patients with uveal melanoma caused severe socket
      contracture and inability to wear a prosthesis in approximately 40% of patients.
      Surgical repair of the contracted socket using oral mucous membrane grafting can
      allow resumption of prosthesis wear.

PMID- 22581086
TI  - Re: "The effect of orbital decompression surgery on lid retraction in thyroid eye
      disease".

PMID- 22581088
TI  - Re: "Intradioploic epidermoid cyst of frontal bone with spontaneous fistulization
      to eyelid".

PMID- 22581090
TI  - Re: "Fibromyxoma masquerading as dacryocystitis".

PMID- 22581092
TI  - Re: "Re: Muscle prolapse after harvesting autogenous fascia lata for frontalis
      suspension in children," by Fry and Naugle.

PMID- 22581093
TI  - "The Inverse Shoe Shine Sign" in transconjunctival lower blepharoplasty with fat
      repositioning.

PMID- 22581094
TI  - Re: "Retinoblastoma associated orbital cellulitis".

PMID- 22581095
TI  - Response to hydroxychloroquine in Japanese patients with lupus-related skin
      disease using the cutaneous lupus erythematosus disease area and severity index
      (CLASI).
AB  - BACKGROUND: Hydroxychloroquine (HCQ) is not available in Japan. To design a
      clinical trial of HCQ, we evaluated the response to HCQ in Japanese patients with
      lupus-related skin disease using the cutaneous lupus erythematosus disease area
      and severity index (CLASI). METHODS: Twenty-seven patients with lupus-related
      skin disease who started HCQ at four hospitals were included. Patients were
      categorized into responders by the CLASI response criteria. The points and the
      rate of improvement in the CLASI activity score after 16 weeks of treatment were
      analyzed, focusing on six parameters: systemic lupus erythematosus (SLE), skin
      manifestations, disease duration, prednisolone, smoking, and severity. RESULTS:
      Twenty-seven patients, including 17 with SLE (6 with SLE/Sjogren's syndrome),
      were analyzed retrospectively. Twenty-three patients (85 %) were categorized as
      responders. The mean CLASI activity score improved from 10.1 to 4.5 (p < 0.0001).
      The improvement rate did not differ in these parameters except for that of
      annular erythema (81.6 versus 34.3 %, p = 0.036). On multivariate analysis, the
      baseline CLASI activity score (CLASI >=9) correlated with the greatest decrease
      in CLASI activity score (F = 69.7, p < 0.0001). CONCLUSIONS: CLASI is a reliable
      indicator to evaluate the efficacy of the drug, and HCQ is an effective treatment
      for Japanese patients with lupus-related skin disease.

PMID- 22581096
TI  - Peribulbar block in patients scheduled for eye procedures and treated with
      clopidogrel.
AB  - Our hypothesis was that the continuation of clopidogrel does not increase the
      risk of eye hemorrhage, compared to patients not treated with clopidogrel, when a
      peribulbar anesthesia is required. Our prospective case-control study enrolled
      two groups of 1,000 patients scheduled for intraocular eye surgery requiring a
      peribulbar block. Patients treated with clopidogrel were included in group A
      (1,000 patients). Patients who had never been treated with clopidogrel
      constituted the control group (group B, 1,000 patients). Hemorrhages were graded
      as follows: 1 = spot ecchymosis of eyelid and or subconjunctival hemorrhage; 2 =
      eyelid ecchymosis involving half the lid surface area; 3 = eyelid ecchymosis all
      around the eye, no increase in intraocular pressure; 4 = retrobulbar hemorrhage
      with increased intraocular pressure. Grade 1 hemorrhages were observed in 30
      patients (3.0 %) in group A and in 20 patients (2.0 %) in group B. No grade 2, 3,
      or 4 hemorrhage was encountered. There was no significant difference in the
      grading of hemorrhage between the groups (p = 0.017). Clopidogrel was not
      associated with a significant increase in potentially sight-threatening local
      anesthetic complications.

PMID- 22581098
TI  - Poisonings and clinical toxicology: a template for Ireland.
AB  - BACKGROUND: Poisons information is accessed around the clock in the British Isles
      from six centres of which two are in Ireland at Dublin and Belfast accompanied by
      consultant toxicologist advisory service. The numbers of calls in Ireland are
      down to about 40 per day due to easy access to online data bases. Access to
      Toxbase, the clinical toxicology database of the National Poisons Information
      Service is available to National Health Service (NHS) health professionals and to
      Emergency Departments and Intensive Care units in the Republic of Ireland. There
      are 59 Toxbase users in the Republic of Ireland and 99 % of activity originates
      in Emergency Departments. All United States Poison Control Centres primarily use
      Poisindex which is a commercial database from Thomson Reuters. RESULTS:
      Information on paracetamol, diazepam, analgesics and psycho-active compounds are
      the commonest queries. Data from telephone and computer accesses provide an
      indicator of future trends in both licit and illicit drug poisons which may
      direct laboratory analytical service developments. Data from National Drug
      Related Deaths Index is the most accurate information on toxicological deaths in
      Ireland. Laboratory toxicology requirements to support emergency departments are
      listed. CONCLUSIONS: Recommendations are made for a web-based open access Toxbase
      or equivalent; for a co-location of poisons information and laboratory clinical
      toxicology; for the establishment of a National Clinical Toxicology Institute for
      Ireland; for a list of accredited medical advisors in clinical toxicology; for
      multidisciplinary case conferences in complex toxicology cases for coroners; for
      the establishment of a national clinical toxicology referral out-patients service
      in Ireland.

PMID- 22581099
TI  - First ladies in laying the foundation of neuroendocrinology.
AB  - Although women were welcomed into medical practice in increasing numbers by the
      close of the nineteenth century, it was not until the second quarter of the
      twentieth century that they were recognised as valuable collaborators and
      contributors in the nascent field of neuroendocrinology, wherein they soon made
      advances that have stood the test of time. Mary Pickford at Edinburgh measured
      the action of acetyl choline in the supraoptic nucleus of the hypothalamus and
      helped to establish that vasopressin and oxytocin are formed in separate and
      distinct neurons. Berta Scharrer, like her future husband Ernest Scharrer, was
      born in Munich. Their great contribution was the proof that the posterior
      pituitary is not a gland, but the location of the release into the circulation of
      vasopressin and oxytocin from fibres in the hypothalamico-hypophysial tract.
      Their work succeeded in establishing against high-powered, vehement opposition
      the value of histological evidence in elucidating synthesis, storage and release
      of secretion from neuro-endocrine cells. A Rockefeller travelling fellowship
      allowed Marthe Vogt to move from Berlin in 1932 to London and then to Cambridge.
      The relations between the cortex and medulla of the suprarenal gland and the
      control of adrenocorticotropin were her main concerns. Dora Jacobsohn emigrated
      to Sweden after graduating in Berlin in 1934. She investigated control of the
      anterior pituitary gland by the hypothalamus, and co-operated with Geoffrey
      Harris in establishing the role of the hypothalamico-hypophysial portal venous
      system that conveys the releasing factors that preside over anterior pituitary
      cells. Laboratory discoveries do not constitute the whole of science, for the
      interpretation of evidence and recognition of general principles deserve
      attention. Dorothy Price, from Aurora, Illinois, received her BS in 1922 at the
      University of Chicago, and was glad to find employment as a histology technician
      in the zoology laboratory, where she was quietly appropriated by Carl Moore (1892
      1955), an investigator seeking the key to hormonal control of gonadal function.
      The burning question was the part played by what was (then) called hormone
      antagonism in the biology of the testis. Price recognised that the common factor
      in explaining the deleterious effects of oestrin and testosterone on the testes
      could be traced to the anterior pituitary: the pituitary controlled testicular
      secretion, and the male hormone in turn controlled gonadotropin release in the
      pituitary. This seesaw balance explained the problem, and was the first of many
      regulatory systems to be recognised as ensuring stability--and later became known
      as negative feedback. The contributions of these five women helped place neuro
      endocrinology on a firm foundation for its later expansion.

PMID- 22581100
TI  - Molecular mechanism of the enhanced virulence of 2009 pandemic influenza A (H1N1)
      virus from D222G mutation in the hemagglutinin: a molecular modeling study.
AB  - D222G mutation of the hemagglutinin (HA) is of special interest because of its
      close association with the enhanced virulence of 2009 pandemic influenza A (H1N1)
      virus through the increased binding affinity to alpha2,3-linked sialylated glycan
      receptors. However, there is still a lack of detailed understanding about the
      molecular mechanism of this enhanced virulence. Here, molecular dynamics
      simulation and binding free energy calculation were performed to explore the
      altered glycan receptor binding mechanism of HA upon the D222G mutation by
      studying the interaction of one alpha2,3-linked sialylglycan (sequence: SIA-GAL
      NAG) with the wild type and D222G mutated HA. The binding free energy calculation
      based on the molecular mechanics generalized Born surface area (MM-GBSA) method
      indicates that the D222G mutated HA has a much stronger binding affinity with the
      studied alpha2,3-linked glycan than the wild type. This is consistent with the
      experimental result. The increased binding free energy of D222G mutant mainly
      comes from the increased energy contribution of Gln223. The structural analysis
      proves that the altered electrostatic potential of receptor binding domain (RBD)
      and the increased flexibility of 220-loop are the essential reasons leading to
      the increased affinity of HA to alpha2,3-linked sialic acid glycans. The obtained
      results of this study have allowed a deeper understanding of the receptor
      recognition mechanism and the pathogenicity of influenza virus, which will be
      valuable to the structure-based inhibitors design targeting influenza virus entry
      process.

PMID- 22581101
TI  - Response surface methodology in docking study of small molecule BACE-1
      inhibitors.
AB  - Computational evaluation of ligand-receptor binding via docking strategy is a
      well established approach in structure-based drug design. This technique has been
      applied frequently in developing molecules of biological interest. However, any
      procedure would require an optimization set up to be more efficient, economic and
      time-saving. Advantages of modern statistical optimization methods over
      conventional one-factor-at-a-time studies have been well revealed. The
      optimization by experimental design provides a combination of factor levels
      simultaneously satisfying the requirements considered for each of the responses
      and factors. In this study, response surface method was applied to optimize the
      prominent factors (number of genetic algorithm runs, population size, maximum
      number of evaluations, torsion degrees for ligand and number of rotatable bonds
      in ligand) in AutoDock4.2-based binding study of small molecule beta-secretase
      inhibitors as anti-alzheimer agents. Results revealed that a number of rotatable
      bonds in ligand and maximum number of docking evaluations were determinant
      variables affecting docking outputs. The interference between torsion degrees for
      ligand and number of genetic algorithm runs for docking procedure was found to be
      the significant interaction term in our model. Optimized docking outputs
      exhibited a high correlation with experimental fluorescence resonance energy
      transfer-based IC50s for beta-secretase inhibitors (R2 = 0.9133).

PMID- 22581102
TI  - Air quality status during Diwali festival of India: a case study.
AB  - The PM(2.5) and PM(10) samples were collected during Diwali celebration from
      study area and characterized for ionic concentration of four anions (NO(3) (-),
      NO(2) (-), Cl(-), SO(4) (2-)) and five cations (K(+), Mg(2+), NH(4) (+), Ca(2+),
      Na(+)). The results showed that the ionic concentrations were three times
      compared to those on pre and post Diwali days. Predominant ions for PM(2.5) were
      K(+) 33.7 MUg/m(3), Mg(+) 31.6 MUg/m(3), SO(4) (2-) 22.1 MUg/m(3), NH(4) (+) 17.5
      MUg/m(3) and NO(3) (-) 18 MUg/m(3) and for PM(10) the ionic concentrations were
      Mg(+) 29.6 MUg/m(3), K(+) 26 MUg/m(3), SO(4) (2-) 19.9 MUg/m(3), NH(4) (+) 16.8
      MUg/m(3) and NO(3) (-) 16 MUg/m(3). While concentration of SO(2) and NO(2) were
      17.23, 70.33 MUg/m(3) respectively.

PMID- 22581103
TI  - Microvessel density is high in clear-cell renal cell carcinomas of Ukrainian
      patients exposed to chronic persistent low-dose ionizing radiation after the
      Chernobyl accident.
AB  - During the 25-year period subsequent to the Chernobyl accident, the morbidity of
      malignant renal tumors in Ukraine has increased from 4.7 to 10.7 per 100,000 of
      the total population. Recent studies of our group have shown that increases in
      morbidity, aggressiveness, and proliferative activity of renal cell carcinomas
      (RCCs), especially clear-cell renal cell carcinoma (CCRCC), in Ukrainian patients
      continuously inhabiting the radio-contaminated areas could be explained by
      specific molecular changes influenced by the so-called "chronic persistent low
      dose ionizing radiation" (CPLDIR) exposure. This study aimed to examine the role
      of angiogenesis in CCRCC carcinogenesis associated with CPLDIR in patients living
      more than 20 years in cesium 137 ((137)Cs) contaminated areas after the Chernobyl
      accident in Ukraine. Paraffin-embedded specimens of 106 CCRCs were studied:
      Control cases were 18 tumors from Spanish patients (group 1), 25 tumors from
      Ukrainian patients from so-called clean areas without known radio-contamination
      (group 2), and 63 tumors from Ukrainian patients from radio-contaminated areas
      (group 3). For intratumoral microvessel density (MVD) determination, anti-CD31
      antibody was used. A computerized image analysis program was used to
      quantitatively calculate the vascular density. Seventy-three percent of group 3
      and 72 % of group 2 CCRCCs displayed the highest MVD. A striking increase in MVD
      was seen in group 3 CCRCCs, in comparison with groups 1 and 2 (p < 0.001). The
      majority of the hot spot vessels in group 3 was poorly differentiated. Moreover,
      MVD values for total vessels as well as for capillaries and tumor grade were
      strongly correlated. When we compared only tumor-node-metastasis tumor stages I
      and II, the differences remained statistically significant (p < 0.1). The ratio
      of the average total vessels and capillaries in the Ukrainian groups combined was
      1.65:1 in comparison to the Spanish group. Our results provide evidence that
      CPLDIR exposure increases MVD (particularly capillary) in CCRCCs and is
      associated with a higher histological grade.

PMID- 22581104
TI  - Antidepressants may mitigate the effects of prenatal maternal anxiety on infant
      auditory sensory gating.
AB  - OBJECTIVE: Prenatal maternal anxiety has detrimental effects on the offspring's
      neurocognitive development, including impaired attentional function.
      Antidepressants are commonly used during pregnancy, yet their impact on offspring
      attention and their interaction with maternal anxiety has not been assessed. The
      authors used P50 auditory sensory gating, a putative marker of early attentional
      processes measurable in young infants, to assess the impact of maternal anxiety
      and antidepressant use. METHOD: A total of 242 mother-infant dyads were
      classified relative to maternal history of anxiety and maternal prenatal
      antidepressant use. Infant P50 auditory sensory gating was recorded during active
      sleep at a mean age of 76 days (SD=38). RESULTS: In the absence of prenatal
      antidepressant exposure, infants whose mothers had a history of anxiety diagnoses
      had diminished P50 sensory gating. Prenatal antidepressant exposure mitigated the
      effect of anxiety. The effect of maternal anxiety was limited to amplitude of
      response to the second stimulus, while antidepressant exposure had an impact on
      the amplitude of response to both the first and second stimulus. CONCLUSIONS:
      Maternal anxiety disorders are associated with less inhibition during infant
      sensory gating, a performance deficit mitigated by prenatal antidepressant
      exposure. This effect may be important in considering the risks and benefits of
      antidepressant use during pregnancy. Cholinergic mechanisms are hypothesized for
      both anxiety and antidepressant effects, although the cholinergic receptors
      involved are likely different for anxiety and antidepressant effects.

PMID- 22581105
TI  - A platform for characterizing therapeutic monoclonal antibody breakdown products
      by 2D chromatography and top-down mass spectrometry.
AB  - With the growing commercialization of therapeutic monoclonal antibodies developed
      for the treatment of various diseases comes the need for increased analytical
      scrutiny of the impurity components contained within such drug products.
      Traditionally, relatively low performance and throughput analytical techniques
      were employed for elucidating the product-related breakdown components derived
      from the original molecule, including N-terminal Edman sequencing and matrix
      assisted laser desorption time-of-flight (MALDI-TOF) mass spectrometry. Although
      N-terminal sequencing provides a definitive starting point of an unknown
      breakdown product, the resolution and mass accuracy of MALDI-TOF instruments are
      often insufficient for unambiguous sequence characterization. Described here is
      the implementation of existing advanced analytical technologies, including high
      performance mass spectrometry (LTQ-Orbitrap XL-ETD) and a chip-based
      nanoelectrospray autosampling robot (TriVersa NanoMate), for the thorough
      identification and characterization of breakdown products derived from a force
      degraded monoclonal antibody. Many anticipated breakdown products were
      identified, including Fab fragment (48,325 Da) and heavy chain polypeptide
      hydrolysis product (15,521 Da). Using high-resolution collisionally induced and
      electron transfer dissociation methods, additional identifications were made with
      specific localization of unpredicted modifications. As examples, a modified Fab
      fragment (N- and C-terminal cyclization, 47,902 Da) and a hydrolyzed free light
      chain impurity components (23,191 Da) were identified with a high degree of
      confidence (E value, <1e-5). This work describes the approach for top-down
      characterization of breakdown products and is readily applicable to additional
      monoclonal antibodies (mAb) characterization experiments, including charge
      isoform characterization and aggregate analysis, for a more thorough
      understanding of therapeutic mAb drug products.

PMID- 22581106
TI  - Selenium-vitamin E combination modulates endometrial lipid peroxidation and
      antioxidant enzymes in streptozotocin-induced diabetic rat.
AB  - Diabetes mellitus is associated with diabetic impairment of uterine function,
      ultimately leading to reduced fertility. Its etiology may involve oxidative
      damage by reactive oxygen substances, and protection against this damage can be
      offered by antioxidant supplementation. In the present study, the effects of a
      vitamin E-plus-selenium (VESe) combination on lipid peroxidation (MDA) and the
      scavenging enzyme activity in the uterine endometrium of streptozotocin (STZ)
      induced diabetic rats were investigated. Twenty-four female rats were equally
      divided into three groups as follows: group I (control); group II (diabetic);
      group III (diabetic + VESe), STZ + vitamin E (60 mg/kg over 1 day) + selenium
      treated (Na2SeO3, 1 mg/kg over 1 day). After 4 weeks of receiving the VESe
      treatment, endometrium samples were taken from the uterus. Although the VESe
      treatment decreased the MDA and blood glucose levels in the STZ group, the
      observed values remained significantly higher than in the controls. Catalase,
      superoxide dismutase, and glutathione peroxidase activities and body weight gain
      were significantly (p < 0.01) lower in STZ groups as compared to control group,
      whereas their activities were (p < 0.01) increased by VESe treatment. However,
      there was no significant difference on body weight gain and uterine weights
      between control and STZ + VESe groups. In conclusion, the endometrial
      complications caused by oxidative stress, and the abnormal blood glucose levels
      in diabetic of rats, can be alleviated by strengthening the physiological
      antioxidative defense through the administration of vitamin E and Se.

PMID- 22581107
TI  - Impact of depression and anxiety on the quality of life of constipated patients.
AB  - Constipation negatively affects quality of life (QOL), however, the specific
      mechanisms through which this relationship occurs are unclear. The present study
      examined anxiety and depression as potential mediators of the relationship
      between constipation severity and QOL in a sample of 142 constipated patients.
      Results indicated that depression symptom severity mediated the relationship
      between constipation severity and mental health-related QOL. For patients meeting
      diagnostic criteria for Major Depressive Disorder, indirect effects were observed
      in the relationship between constipation severity and both physical and mental
      health-related QOL. Anxiety did not contribute to this model. Treating depression
      may be useful in improving QOL in severely constipated patients, which highlights
      the importance of psychological screening and treatment referrals in primary care
      settings.

PMID- 22581108
TI  - Health-related quality of life is associated with positive affect in patients
      with coronary heart disease entering cardiac rehabilitation.
AB  - Health-related quality of life (QoL) is an important and widely used outcome
      measure in cardiac populations. We examined the relationship between positive
      affect and health-related quality of life, controlling for traditional
      cardiovascular risk factors, clinical variables and negative affect. We further
      investigated the role of gender in this relationship given the well-known gender
      differences in cardiovascular health. We enrolled 746 patients with coronary
      heart disease (CHD) before they entered outpatient cardiac rehabilitation. All
      patients completed the Global Mood Scale and the SF-36 Health Survey. Positive
      affect was independently associated with mental (p < .001) and physical QoL (p <
      .001) after controlling for control variables. Gender moderated the relationship
      between positive affect and physical QoL (p = .009) but not mental QoL (p = .60).
      Positive affect was positively associated with physical QoL in men (p < .001) but
      not in women (p = .44). The health-related QoL of patients with CHD is associated
      with a person's level of positive affect.

PMID- 22581109
TI  - Characterization of a high-resolution hybrid DOI detector for a dedicated breast
      PET/CT scanner.
AB  - The aim of this study is to design and test a new high-resolution hybrid depth of
      interaction (DOI) detector for a dedicated breast PET/CT scanner. Two detectors
      have been designed and built. The completed detectors are based on a 14 * 14
      array of 1.5 * 1.5 * 20 mm(3) unpolished lutetium orthosilicate scintillation
      crystals, with each element coated in a 50 MUm layer of reflective material. The
      detector is read out from both ends using a position-sensitive photomultiplier
      tube (PSPMT) and a large active area (20 * 20 mm(2)) avalanche photodiode (APD)
      to enable acquisition of DOI information. Nuclear instrumentation modules were
      used to characterize the detectors' performances in terms of timing, intrinsic
      spatial resolution (ISR) and energy resolution, as well as DOI resolution with a
      dual-ended readout configuration. Measurements with the APD were performed at a
      temperature of 10  degrees C. All crystals were identified at all depths, even
      though the signal amplitude from the PSPMT decreases with depth away from it. We
      measured a timing resolution of 2.4 ns, and an average energy resolution of 19%.
      The mean ISR was measured to be 1.2 mm for crystals in the central row of the
      array for detectors in the face-to-face position. Two off-center positions were
      measured corresponding to 26 degrees  and 51 degrees  oblique photon incidence,
      and the mean ISR at these positions was 1.5 and 1.7 mm, respectively. The average
      DOI resolution across all crystals and depths was measured to be 2.9 mm
      (including the beam width of 0.6 mm). This detector design shows good promise as
      a high-resolution detector for a dedicated breast PET/CT scanner.

PMID- 22581110
TI  - Modulation of lysozyme activity by lead administered by different routes. In
      vitro study and analysis in blood, kidney, and lung.
AB  - Modifications in the enzyme activity of lysozyme, a protein implied in the
      defence barrier of the organism, can be a good biomarker of alterations in the
      immune system as a result of exposure to toxic metal, such as lead. The aim of
      this work was to evaluate the effect of a 200 ppm dose of lead on lysozyme
      activity in blood, kidney, and lung, and also on tissue structure. Previously,
      the effect of lead acetate on lysozyme activity in vitro was determined; the in
      vitro results indicated that lead produced a decrease in enzyme activity. The
      activity loss was 16 % at 200 ppm of lead. Lead acetate was administered to
      Wistar rats by oral and intraperitoneal injections. An increase in lysozyme
      activity was observed in blood when lead was administered by introperitoneal
      route and in kidney by the oral route. The possible immunostimulation in kidney
      was discarded because of the structural alterations observed in the tissue. In
      lung, the decrease in specific lysozyme activity, for both routes of lead
      exposure, seems to indicate immunosupression, which was in accordance with the
      structural alterations observed in this tissue.

PMID- 22581111
TI  - Effects of green tea supplementation on elements, total antioxidants, lipids, and
      glucose values in the serum of obese patients.
AB  - The consumption of green tea has been associated with cardiovascular and
      metabolic diseases. There have been some studies on the influence of green tea on
      the mineral status of obese subjects, but they have not yielded conclusive
      results. The aim of the present study is to examine the effects of green tea
      extract on the mineral, body mass, lipid profile, glucose, and antioxidant status
      of obese patients. A randomized, double-blind, placebo-controlled study was
      conducted. Forty-six obese patients were randomly assigned to receive either 379
      mg of green tea extract, or a placebo, daily for 3 months. At baseline, and after
      3 months of treatment, the anthropometric parameters, blood pressure, and total
      antioxidant status were assessed, as were the levels of plasma lipids, glucose,
      calcium, magnesium, iron, zinc, and copper. We found that 3 months of green tea
      extract supplementation resulted in decreases in body mass index, waist
      circumference, and levels of total cholesterol, low-density cholesterol, and
      triglyceride. Increases in total antioxidant level and in zinc concentration in
      serum were also observed. Glucose and iron levels were lower in the green tea
      extract group than in the control, although HDL-cholesterol and magnesium were
      higher in the green tea extract group than in the placebo group. At baseline, a
      positive correlation was found between calcium and body mass index, as was a
      negative correlation between copper and triglycerides. After 3 months, a positive
      correlation between iron and body mass index and between magnesium and HDL
      cholesterol, as well as a negative correlation between magnesium and glucose,
      were observed. The present findings demonstrate that green tea influences the
      body's mineral status. Moreover, the results of this study confirm the beneficial
      effects of green tea extract supplementation on body mass index, lipid profile,
      and total antioxidant status in patients with obesity.

PMID- 22581112
TI  - Regulated chemokine gene expression in mouse mesothelioma and mesothelial cells:
      TNF-alpha upregulates both CC and CXC chemokine genes.
AB  - Many cancers express an array of chemokines which have the capacity to modulate
      the nature and function of intratumoural leukocyte infiltrates. In malignant
      mesothelioma (MM) neither the chemokine signalling networks nor their regulation
      have been investigated despite the prominence of leucocytic infiltrates in both
      clinical and experimental tumours. In this study, we examined constitutive and
      cytokine-regulated expression of CC and CXC chemokine genes in mesothelioma and
      mesothelial cell cultures derived from two different mouse strains (BALB/C and
      CBA/CaH). In mouse MM and mesothelial cells MCP-1/JE, GRO-alpha/KC and RANTES
      were expressed whereas MIP-1alpha and MIP-2 were infrequently expressed.
      Comparison of basal chemokine expression showed that GRO-alpha/KC mRNA was
      overexpressed in the malignant cells whereas MCP-1 gene expression and release
      was downregulated. Treatment of mesothelioma cells with IL-4, IFN-gamma or TNF
      alpha revealed that chemokine genes could be more responsive to cytokines in the
      malignant compared to their mesothelial cells. TNF-alpha was consistently the
      most potent positive regulator of both CC and CXC chemokine expression and MCP-1
      release. The present study for the first time provides a mechanistic insight into
      the differential regulation of chemokine expression in malignant mesothelioma
      cells and has implications for mesothelial chemokine signalling in mouse models.

PMID- 22581113
TI  - Molecular hydrogelators of peptoid-peptide conjugates with superior stability
      against enzyme digestion.
AB  - We report on molecular hydrogelators based on peptoid-peptide conjugates with
      good biocompatibility to different cells and superior stability against
      proteinase K digestion.

PMID- 22581114
TI  - Painful subcutaneous nodule of the arm. Extradigital glomus tumor (subcutaneous
      glomus tumor of the arm).

PMID- 22581115
TI  - An IL-12/Shh-C domain fusion protein-based IL-12 autocrine loop for sustained
      natural killer cell activation.
AB  - The dependency of activated natural killer (NK) cells on the continuous support
      of exogenous interleukin (IL)-2 for their in vivo survival, tumor localization
      and consequently, their antitumor effect, is a major obstacle for NK cell
      mediated tumor therapy. In the present study, a fusion gene between IL-12 and
      mouse sonic hedgehog C-terminal domain (Shh-C) was constructed. The fusion
      protein was autocatalytically processed to form cholesterol-modified IL-12
      molecules and an autocrine loop of IL-12 was established for the sustained
      activation of NK cells. The transduced NK cells matured more rapidly in vitro
      with the enhanced expression of granule-related proteins. NKIL-12/Shh-C cells
      reached the same proliferation rate as NK cells transduced with enhanced green
      fluorescent protein (EGFP)/Shh-C (NKEGFP/Shh-C) with <10-fold IL-2
      supplementation, suggesting that the fusion protein reduced the dependency of NK
      cells on IL-2. The amount of interferon-gamma (IFN-gamma) in the supernatants of
      NKIL-12/Shh-C cells 5 and 7 days after transduction was significantly higher than
      that in the supernatants of NKIL-12 cells. Immunofluorescent staining of lung
      tissues from B16-bearing mice which had received an intravenous injection of
      lentivirus-transduced NK cells without exogenous IL-2 confirmed that donor NK
      cells successfully infiltrated into the lung tissues. The survival time of the
      mice which had received NKIL-12/Shh-C cells was significantly prolonged compared
      to the mice which had received NKEGFP/Shh-C cells.

PMID- 22581116
TI  - Accuracy and repeatability of self-measurement of interpupillary distance.
AB  - PURPOSE: To determine the accuracy and repeatability of participants determining
      their own interpupillary distance (PD). METHODS: Fifty-two healthy and naive
      participants were enrolled and analyzed. All participants analyzed were without
      strabismus. Participants had PD measurements taken by a trained examiner using
      both a PD rule and an optical pupillometer. Participants then, following online
      instructions measured their own PD in a mirror, measured a friend's PD and used
      an online application downloaded to an IPod. Measurements were repeated twice for
      each type, and the pupillometer results were considered the gold standard
      (referent). RESULTS: The mean difference between the examiner PD rule measurement
      and the pupillometer were +0.59 mm [95% limits of agreement (LoA) -0.69 to
      +1.88], pupillometer-self +0.46 mm (-5.22 to +6.14), pupillometer-friend +2.00 mm
      (-3.80 to +7.81), and pupillometer-App -3.24 mm (-3.09 to +9.57). Measurements of
      repeatability using the 95% LoA for the examiner are -0.79 to 0.73 mm for the
      pupillometer and -1.04 to +1.20 mm for the PD rule. Participants' repeatability
      for the self-measurement (mirror) was -3.61 to +4.75 mm, employing a friend was 
      3.74 to +3.94 mm, and using the IPod application was -6.63 to +6.51 mm.
      CONCLUSIONS: Participants' ability to measure their own PD using techniques and
      applications available via the Internet result in poor accuracy and poor
      repeatability.

PMID- 22581117
TI  - Corneal staining and cell shedding during the development of solution-induced
      corneal staining.
AB  - PURPOSE: This non-dispensing cross-over study was conducted to determine if
      lenses presoaked in Opti-Free RepleniSH (OFR) or ReNu MultiPlus (RMP) cause
      solution-induced corneal staining (SICS) and subsequent cell sloughing before the
      typical 2 h in vivo examination point. METHODS.: Study lenses (PureVision) were
      worn bilaterally by 13 participants for periods of 15, 30, 60, and 120 min using
      two different contralateral care regimen pairings. The lens worn on the test eye
      was soaked overnight in either OFR or RMP and the control eye in Clear Care (CC).
      After lens removal, corneal staining was rated on a scale of 0 (negligible) to
      100 (severe) for four peripheral quadrants and the central region, and the
      differential global staining score was calculated by subtracting baseline
      staining scores. Following the staining assessment, corneal cells were collected
      from the ocular surface using a non-contact irrigation system to determine ocular
      cell shedding rates. RESULTS: Differential global staining score with OFR was
      greater than CC with the differences being statistically significant at 30 and 60
      min (p < 0.01). Maximum staining with RMP was significantly greater than OFR and
      peaked after 60 and 120 min of lens wear (p < 0.01). On average, 710 +/- 470
      ocular cells were collected after lens wear, with similar shedding seen
      independent of solution or lens wear duration (p > 0.05). CONCLUSIONS: SICS
      occurred earlier but to a significantly lower degree when PureVision lenses were
      presoaked in OFR compared with RMP, while lenses presoaked in CC did not cause
      SICS. Ocular surface cell shedding after lens removal was not impacted by lens
      wear durations of <=2 h.

PMID- 22581118
TI  - The impact of tear film components on in vitro lipid uptake.
AB  - PURPOSE: To analyze the influence of various tear film components on in vitro
      deposition of two lipids (cholesterol and phosphatidylcholine) on three contact
      lens materials. METHODS: Etafilcon A, balafilcon A, and senofilcon A were
      incubated in four different incubation solutions for 3 or 14 days: an artificial
      tear solution containing lipids and proteins, a protein tear solution containing
      proteins and the lipid of interest, a lipid tear solution containing lipids and
      no proteins, and a single lipid tear solution containing the lipid of interest
      only. Each incubation solution contained one of the two radiolabeled lipids: C
      cholesterol (C) or C-phosphatidylcholine (PC). After soaking, lenses were removed
      from the incubation solution, the lipids were extracted and quantified using a
      beta counter, and masses of lipid were calculated using standard calibration
      curves. RESULTS: This experiment examined several different parameters
      influencing lipid deposition on contact lenses, including lens material, length
      of incubation, and the composition of the incubation solution. Overall, lipid
      deposited differently on different lens materials (p < 0.0005), with the order of
      deposition most commonly being balafilcon > senofilcon > etafilcon. Incubation
      solution had a large impact on how much lipid was deposited (p < 0.00001),
      although cholesterol and phosphatidylcholine demonstrated different deposition
      patterns. Lipid deposition after 14 days of incubation was consistently greater
      than after 3 days (p < 0.02). CONCLUSIONS: This in vitro study demonstrates that
      C and PC deposition are cumulative over time and that silicone hydrogel materials
      deposit more lipid than group IV conventional hydrogel materials. It also clearly
      demonstrates that deposition of C and PC is influenced by the composition of the
      incubation solution and that in vitro models must use more physiologically
      relevant incubation solutions that mimic the natural tear film if in vitro data
      is to be extrapolated to the in vivo situation.

PMID- 22581119
TI  - Prentice award lecture 2011:  removing the brakes on plasticity in the amblyopic
      brain.
AB  - Experience-dependent plasticity is closely linked with the development of sensory
      function. Beyond this sensitive period, developmental plasticity is actively
      limited; however, new studies provide growing evidence for plasticity in the
      adult visual system. The amblyopic visual system is an excellent model for
      examining the "brakes" that limit recovery of function beyond the critical
      period. While amblyopia can often be reversed when treated early, conventional
      treatment is generally not undertaken in older children and adults. However, new
      clinical and experimental studies in both animals and humans provide evidence for
      neural plasticity beyond the critical period. The results suggest that perceptual
      learning and video game play may be effective in improving a range of visual
      performance measures and importantly the improvements may transfer to better
      visual acuity and stereopsis. These findings, along with the results of new
      clinical trials, suggest that it might be time to reconsider our notions about
      neural plasticity in amblyopia.

PMID- 22581122
TI  - Chinese herbal therapy for the treatment of food allergy.
AB  - Traditional Chinese medicine (TCM) has been widely used in China to treat various
      diseases for thousands of years. Given its reputed effectiveness, low cost, and
      favorable safety profile, TCM is attracting great interest in Western societies
      as a source of therapy for an array of illnesses, including allergies and asthma.
      Although food allergy has not been described in the TCM literature, a novel
      treatment for food allergy, named the food allergy herbal formula-2 (FAHF-2), was
      developed using TCM principles. Using a well-characterized murine model of peanut
      allergy, FAHF-2 has been shown to be highly effective in providing long-term
      protection against peanut-induced anaphylaxis, with a high safety margin. Phase 1
      human trials have demonstrated the safety of FAHF-2 in food allergic individuals.
      Currently, a phase 2 trial examining efficacy of FAHF-2 is on-going. Other TCMs
      also show a potential for treating food allergies in preclinical studies.

PMID- 22581123
TI  - Management strategies in atrial fibrillation in patients with heart failure.
AB  - Atrial fibrillation (AF) and heart failure (HF) frequently occur together, and
      their coexistence is associated with a poor prognosis. AF and HF share risk
      factors, but their relationship involves complex hemodynamic, neurohormonal,
      inflammatory, ultrastructural, and electrophysiologic processes that extend
      beyond epidemiological associations. The shared mechanisms underlying AF and HF
      have important implications for the treatment of AF in patients with HF. This
      article focuses on reviewing contemporary data as it pertains to AF management in
      patients with HF and provides insight into investigational therapies currently
      under development.

PMID- 22581121
TI  - Domain organization differences explain Bcr-Abl's preference for CrkL over CrkII.
AB  - CrkL is a key signaling protein that mediates the leukemogenic activity of Bcr
      Abl. CrkL is thought to adopt a structure that is similar to that of its CrkII
      homolog. The two proteins share high sequence identity and indistinguishable
      ligand binding preferences, yet they have distinct physiological roles. Here we
      show that the structures of CrkL and phosphorylated CrkL are markedly different
      than the corresponding structures of CrkII. As a result, the binding activities
      of the Src homology 2 and Src homology 3 domains in the two proteins are
      regulated in a distinct manner and to a different extent. The different
      structural architecture of CrkL and CrkII may account for their distinct
      functional roles. The data show that CrkL forms a constitutive complex with Abl,
      thus explaining the strong preference of Bcr-Abl for CrkL. The results also
      highlight how the structural organization of the modular domains in adaptor
      proteins can control signaling outcome.

PMID- 22581124
TI  - Inheritance of the VATER/VACTERL association.
AB  - VATER/VACTERL association refers to the non-random co-occurrence of the following
      component features: vertebral defects, anal atresia, cardiac malformations,
      tracheoesophageal atresia, renal abnormalities, and limb defects. Recently,
      Solomon et al. (Hum Genet 127:731-733, 2010) observed an increased prevalence of
      component features among first-degree relatives of VATER/VACTERL patients
      suggesting that in some patients, the disorder may be inherited. To replicate
      these findings, we investigated 87 VATER/VACTERL patients with the presence of a
      minimum of three component features and their first-degree relatives (n = 271).
      No increase in the overall prevalence of component features was observed in first
      degree relatives compared to the general population (chi2 = 2.68, p = 0.10).
      Separate analysis for the prevalence of single component features showed a higher
      prevalence of tracheoesophageal fistula/atresia among first-degree relatives
      compared to the general population (OR 17.65, 95% CI 2.47-126.05). However, this
      was based on occurrence in one family only. Our findings suggest that although
      familial occurrence renders a genetic contribution likely, the overall risk of
      recurrence among the first-degree relatives of patients with VATER/VACTERL
      association is probably very low. Since the patients in the present study were
      young and no offspring could be studied, estimation of the role of de novo
      mutations in the development of VATER/VACTERL was not possible.

PMID- 22581126
TI  - The unidirectional testicular tunneller: a simple, safe and novel device for
      orchidopexy in patients with palpable undescended testes.
AB  - PURPOSE: Inguinal orchidopexy is already considered a safe procedure, this paper
      describes a simple new surgical instrument designed to make the operation easier,
      simpler and quicker, whilst reducing tissue trauma, in particular to the deep
      ring. The result of its use in two centres is presented. METHODS: A
      unidirectional testicular tunneller has been developed comprising a head, shaft
      and eye. At operation, following testicular mobilisation, the tunneller is passed
      through the groin incision into the scrotum and a dartos pouch created by cutting
      against the head of the instrument. This allows more of a "no-touch" technique
      with less back and forth movement through the inguinal canal. The testis is
      attached to the eye of the instrument and pulled into the scrotum before
      fixation. RESULTS: From November 2000 to December 2011, two surgeons operated on
      592 boys using the instrument. 93 procedures were bilateral. All operations
      proceeded without incident and a healthy testis was safely and permanently placed
      in the scrotum. There were no complications related to the use of the tunneller.
      All were treated as day cases. CONCLUSION: The instrument described in this paper
      simplifies inguinal orchidopexy, improves procedural safety and is felt to reduce
      surgical trauma. In view of these advantages and the absence of complications
      related to this instrument, its use in inguinal orchidopexy is recommended.

PMID- 22581127
TI  - Magnetic control system targeted for capsule endoscopic operations in the stomach
      -design, fabrication, and in vitro and ex vivo evaluations.
AB  - This paper presents a novel solution of a hand-held external controller to a
      miniaturized capsule endoscope in the gastrointestinal (GI) tract. Traditional
      capsule endoscopes move passively by peristaltic wave generated in the GI tract
      and the gravity, which makes it impossible for endoscopists to manipulate the
      capsule endoscope to the diagnostic disease areas. In this study, the main
      objective is to present an endoscopic capsule and a magnetic field navigator
      (MFN) that allows endoscopists to remotely control the locomotion and viewing
      angle of an endoscopic capsule. The attractive merits of this study are that the
      maneuvering of the endoscopic capsule can be achieved by the external MFN with
      effectiveness, low cost, and operation safety, both from a theoretical and an
      experimental point of view. In order to study the magnetic interactions between
      the endoscopic capsule and the external MFN, a magnetic-analysis model is
      established for computer-based finite-element simulations. In addition,
      experiments are conducted to show the control effectiveness of the MFN to the
      endoscopic capsule. Finally, several prototype endoscopic capsules and a
      prototype MFN are fabricated, and their actual capabilities are experimentally
      assessed via in vitro and ex vivo tests using a stomach model and a resected
      porcine stomach, respectively. Both in vitro and ex vivo test results demonstrate
      great potential and practicability of achieving high-precision rotation and
      controllable movement of the capsule using the developed MFN.

PMID- 22581125
TI  - Improved outcomes in paediatric anaesthesia: contributing factors.
AB  - PURPOSE: To discuss developments in paediatric anaesthesia and explore the
      factors which have contributed to improved anaesthetic-related patient outcomes.
      METHODS: Narrative review of findings in the literature retrieved from
      MEDLINE/Pubmed and manual search. RESULTS: Adverse perioperative outcomes related
      to anaesthesia have been extensively debated over the past few decades, with
      studies implicating factors such as major human error and equipment failure. Case
      series and event registries have enlightened physicians on sources of error and
      patient risk factors such as extremes of age, comorbidity and emergent
      circumstances. Anaesthetic-related deaths in children fell from 6.4 per 10,000
      anaesthetics in the early 1950s to as low as 0.1 per 10,000 anaesthetics by the
      end of the century. Advances in anaesthetic agents, techniques, monitoring
      technologies and training programmes in paediatric anaesthesia play a vital role
      in driving this downward trend. CONCLUSION: Despite substantial progress, there
      is still much room for improvement in areas such as adverse-event reporting,
      anaesthetic-related risk and late neurocognitive outcomes. Systematic reviews
      comparing paediatric patient outcomes after neuroaxial block versus general
      anaesthesia are currently unavailable. The future of paediatric anaesthesia will
      most likely be influenced by much-needed large prospective studies, which can
      provide further insight into patient safety and service delivery.

PMID- 22581128
TI  - Robust smoothing of quantitative genomic data using second-generation wavelets
      and bivariate shrinkage.
AB  - Recent high-throughput nucleotide sequencing technologies provide large amounts
      of quantitative genomic data, and thus, biologists currently need to process vast
      quantities of the data on a regular basis. The first step of the process is
      almost always smoothing of the data because biomedical data generally tend to
      contain a lot of noise. In this first step, classical wavelet transforms are
      widely used; however, the second-generation wavelet transform has not been used
      in biomedical studies. Smoothing based on the second-generation wavelets is more
      effective than classical wavelets-based methods because it employs data-dependent
      wavelet functions and does not require predefined explicit base functions. Since
      biomedical data usually lack regularity, it is more useful in biomedical research
      to use the second-generation wavelets than to use the classical wavelets.
      Therefore, we propose a novel smoothing method based on the second-generation
      wavelets and bivariate shrinkage, which enables to determine robust thresholds
      for wavelet-based smoothing, and apply it to synthetic and real genomic data.
      Experimental results demonstrate the effectiveness of the proposed method.

PMID- 22581129
TI  - Uncertainty analysis of ventricular mechanics using the probabilistic collocation
      method.
AB  - Uncertainty and variability in material parameters are fundamental challenges in
      computational biomechanics. Analyzing and quantifying the resulting uncertainty
      in computed results with parameter sweeps or Monte Carlo methods has become very
      computationally demanding. In this paper, we consider a stochastic method named
      the probabilistic collocation method, and investigate its applicability for
      uncertainty analysis in computing the passive mechanical behavior of the left
      ventricle. Specifically, we study the effect of uncertainties in material input
      parameters upon response properties such as the increase in cavity volume, the
      elongation of the ventricle, the increase in inner radius, the decrease in wall
      thickness, and the rotation at apex. The numerical simulations conducted herein
      indicate that the method is well suited for the problem of consideration, and is
      far more efficient than the Monte Carlo simulation method for obtaining a
      detailed uncertainty quantification. The numerical experiments also give
      interesting indications on which material parameters are most critical for
      accurately determining various global responses.

PMID- 22581130
TI  - O-Glycosylation of snails.
AB  - The glycosylation abilities of snails deserve attention, because snail species
      serve as intermediate hosts in the developmental cycles of some human and cattle
      parasites. In analogy to many other host-pathogen relations, the glycosylation of
      snail proteins may likewise contribute to these host-parasite interactions. Here
      we present an overview on the O-glycan structures of 8 different snails (land and
      water snails, with or without shell): Arion lusitanicus, Achatina fulica,
      Biomphalaria glabrata, Cepaea hortensis, Clea helena, Helix pomatia, Limax
      maximus and Planorbarius corneus. The O-glycans were released from the purified
      snail proteins by beta-elimination. Further analysis was carried out by liquid
      chromatography coupled to electrospray ionization mass spectrometry and - for the
      main structures - by gas chromatography/mass spectrometry. Snail O-glycans are
      built from the four monosaccharide constituents: N-acetylgalactosamine,
      galactose, mannose and fucose. An additional modification is a methylation of the
      hexoses. The common trisaccharide core structure was determined in Arion
      lusitanicus to be N-acetylgalactosamine linked to the protein elongated by two 4
      O-methylated galactose residues. Further elongations by methylated and
      unmethylated galactose and mannose residues and/or fucose are present. The
      typical snail O-glycan structures are different to those so far described.
      Similar to snail N-glycan structures they display methylated hexose residues.

PMID- 22581131
TI  - X-ray vector radiography for bone micro-architecture diagnostics.
AB  - The understanding of large biophysical systems at the systems level often depends
      on a precise knowledge of their microstructure. This is difficult to obtain,
      especially in vivo, because most imaging methods are either limited in terms of
      achievable field of view, or make use of penetrating ionizing radiations such as
      x-rays, in which case the resolution is severely limited by the deposited dose.
      Here, we describe a new method, x-ray vector radiography (XVR), which yields
      various types of information about the local orientation, anisotropy and average
      size of the sample microstructures. We demonstrate the feasibility by showing
      first experimental XVRs of human vertebra bone samples, giving information on the
      trabecular structures even with a pixel resolution of half a millimetre, much
      larger than the structures themselves. This last point is critical for the
      development of low-dose measurement methods which will allow for in vivo studies
      and potentially in the future for new medical diagnostics methods of bone
      metabolic disorder diseases such as osteoporosis.

PMID- 22581132
TI  - Adaptive reconstruction of millimeter-wave radiometric images.
AB  - We present a robust method to reconstruct a millimeter-wave image from a passive
      sensor. The method operates directly on the raw samples from the radiometer. It
      allocates for each pixel to be estimated a patch in the space formed by all the
      raw samples of the image. It then estimates the noise in the patch by measuring
      some distances that reflect how far the samples are from forming a piecewise
      smooth surface. It then allocates a weight for each sample that defines its
      contribution in the pixel reconstruction. This is done via a smoothing Kernel
      that enforces the distances to have a piecewise smooth variation inside the
      patch. Results on real datasets show that our scheme leads to more contrast and
      less noise and the shape of an object is better preserved in a constructed image
      compared to state-of-the-art schemes. The proposed scheme produces better results
      even with low integration times, i.e., 10% of the total integration time used in
      our experiments.

PMID- 22581133
TI  - Constant time joint bilateral filtering using joint integral histograms.
AB  - In this brief, we present a constant time method for the joint bilateral
      filtering. First, we propose an image data structure, coined as joint integral
      histograms (JIHs). Extending the classic integral images and the integral
      histograms, it represents the global information of two correlated images. In a
      JIH, the value at each bin indicates an integral determined by the two images.
      Then, the joint bilateral filtering is transformed to computation and
      manipulation of histograms. Utilizing the JIHs, we are capable of joint bilateral
      filtering in constant time. Its performance is validated in a digital photography
      approach using Flash-noFlash image pairs. Compared with the brute-force method,
      the proposed method achieves a speedup factor of 2-3 orders of magnitude while
      producing similar filtering results.

PMID- 22581134
TI  - Oriented modulation for watermarking in direct binary search halftone images.
AB  - In this paper, a halftoning-based watermarking method is presented. This method
      enables high pixel-depth watermark embedding, while maintaining high image
      quality. This technique is capable of embedding watermarks with pixel depths up
      to 3 bits without causing prominent degradation to the image quality. To achieve
      high image quality, the parallel oriented high-efficient direct binary search
      (DBS) halftoning is selected to be integrated with the proposed orientation
      modulation (OM) method. The OM method utilizes different halftone texture
      orientations to carry different watermark data. In the decoder, the least-mean
      square-trained filters are applied for feature extraction from watermarked images
      in the frequency domain, and the naive Bayes classifier is used to analyze the
      extracted features and ultimately to decode the watermark data. Experimental
      results show that the DBS-based OM encoding method maintains a high degree of
      image quality and realizes the processing efficiency and robustness to be adapted
      in printing applications.

PMID- 22581135
TI  - Improvements on "Fast space-variant elliptical filtering using box splines".
AB  - It is well-known that box filters can be efficiently computed using pre
      integration and local finite-differences. By generalizing this idea and by
      combining it with a nonstandard variant of the central limit theorem, we had
      earlier proposed a constant-time or  O(1) algorithm that allowed one to perform
      space-variant filtering using Gaussian-like kernels. The algorithm was based on
      the observation that both isotropic and anisotropic Gaussians could be
      approximated using certain bivariate splines called box splines. The attractive
      feature of the algorithm was that it allowed one to continuously control the
      shape and size (covariance) of the filter, and that it had a fixed computational
      cost per pixel, irrespective of the size of the filter. The algorithm, however,
      offered a limited control on the covariance and accuracy of the Gaussian
      approximation. In this paper, we propose some improvements of our previous
      algorithm.

PMID- 22581136
TI  - Multiresolution motion planning for autonomous agents via wavelet-based cell
      decompositions.
AB  - We present a path- and motion-planning scheme that is "multiresolution" both in
      the sense of representing the environment with high accuracy only locally and in
      the sense of addressing the vehicle kinematic and dynamic constraints only
      locally. The proposed scheme uses rectangular multiresolution cell
      decompositions, efficiently generated using the wavelet transform. The wavelet
      transform is widely used in signal and image processing, with emerging
      applications in autonomous sensing and perception systems. The proposed motion
      planner enables the simultaneous use of the wavelet transform in both the
      perception and in the motion-planning layers of vehicle autonomy, thus
      potentially reducing online computations. We rigorously prove the completeness of
      the proposed path-planning scheme, and we provide numerical simulation results to
      illustrate its efficacy.

PMID- 22581137
TI  - Understanding Discrete Facial Expressions in Video Using an Emotion Avatar Image.
AB  - Existing video-based facial expression recognition techniques analyze the
      geometry-based and appearance-based information in every frame as well as explore
      the temporal relation among frames. On the contrary, we present a new image-based
      representation and an associated reference image called the emotion avatar image
      (EAI), and the avatar reference, respectively. This representation leverages the
      out-of-plane head rotation. It is not only robust to outliers but also provides a
      method to aggregate dynamic information from expressions with various lengths.
      The approach to facial expression analysis consists of the following steps: 1)
      face detection; 2) face registration of video frames with the avatar reference to
      form the EAI representation; 3) computation of features from EAIs using both
      local binary patterns and local phase quantization; and 4) the classification of
      the feature as one of the emotion type by using a linear support vector machine
      classifier. Our system is tested on the Facial Expression Recognition and
      Analysis Challenge (FERA2011) data, i.e., the Geneva Multimodal Emotion Portrayal
      Facial Expression Recognition and Analysis Challenge (GEMEP-FERA) data set. The
      experimental results demonstrate that the information captured in an EAI for a
      facial expression is a very strong cue for emotion inference. Moreover, our
      method suppresses the person-specific information for emotion and performs well
      on unseen data. 

PMID- 22581138
TI  - Global bounded consensus of multiagent systems with nonidentical nodes and time
      delays.
AB  - This paper investigates the global bounded consensus problem of networked
      multiagent systems consisting of nonlinear nonidentical node dynamics with the
      communication time-delay topology. We derive globally bounded controlled
      consensus conditions for both delay-independent and delay-dependent conditions
      based on the Lyapunov-Krasovskii functional method. The proposed consensus
      criteria ensure that all agents eventually move along the desired trajectory in
      the sense of boundedness. Meanwhile, the bounded consensus criteria can be viewed
      as an extension of the case of identical agent dynamics to the case of
      nonidentical agent dynamics. We finally demonstrate the effectiveness of the
      theoretical results by means of a numerical simulation.

PMID- 22581120
TI  - Italian guidelines for primary headaches: 2012 revised version.
AB  - The first edition of the Italian diagnostic and therapeutic guidelines for
      primary headaches in adults was published in J Headache Pain 2(Suppl. 1):105-190
      (2001). Ten years later, the guideline committee of the Italian Society for the
      Study of Headaches (SISC) decided it was time to update therapeutic guidelines. A
      literature search was carried out on Medline database, and all articles on
      primary headache treatments in English, German, French and Italian published from
      February 2001 to December 2011 were taken into account. Only randomized
      controlled trials (RCT) and meta-analyses were analysed for each drug. If RCT
      were lacking, open studies and case series were also examined. According to the
      previous edition, four levels of recommendation were defined on the basis of
      levels of evidence, scientific strength of evidence and clinical effectiveness.
      Recommendations for symptomatic and prophylactic treatment of migraine and
      cluster headache were therefore revised with respect to previous 2001 guidelines
      and a section was dedicated to non-pharmacological treatment. This article
      reports a summary of the revised version published in extenso in an Italian
      version.

PMID- 22581139
TI  - In the Pursuit of Effective Affective Computing: The Relationship Between
      Features and Registration.
AB  - For facial expression recognition systems to be applicable in the real world,
      they need to be able to detect and track a previously unseen person's face and
      its facial movements accurately in realistic environments. A highly plausible
      solution involves performing a "dense" form of alignment, where 60-70 fiducial
      facial points are tracked with high accuracy. The problem is that, in practice,
      this type of dense alignment had so far been impossible to achieve in a generic
      sense, mainly due to poor reliability and robustness. Instead, many expression
      detection methods have opted for a "coarse" form of face alignment, followed by
      an application of a biologically inspired appearance descriptor such as the
      histogram of oriented gradients or Gabor magnitudes. Encouragingly, recent
      advances to a number of dense alignment algorithms have demonstrated both high
      reliability and accuracy for unseen subjects [e.g., constrained local models
      (CLMs)]. This begs the question: Aside from countering against illumination
      variation, what do these appearance descriptors do that standard pixel
      representations do not? In this paper, we show that, when close to perfect
      alignment is obtained, there is no real benefit in employing these different
      appearance-based representations (under consistent illumination conditions). In
      fact, when misalignment does occur, we show that these appearance descriptors do
      work well by encoding robustness to alignment error. For this work, we compared
      two popular methods for dense alignment-subject-dependent active appearance
      models versus subject-independent CLMs-on the task of action-unit detection.
      These comparisons were conducted through a battery of experiments across various
      publicly available data sets (i.e., CK+, Pain, M3, and GEMEP-FERA). We also
      report our performance in the recent 2011 Facial Expression Recognition and
      Analysis Challenge for the subject-independent task. 

PMID- 22581140
TI  - An effective feature selection method via mutual information estimation.
AB  - This paper proposes a new feature selection method using a mutual information
      based criterion that measures the importance of a feature in a backward selection
      framework. It considers the dependency among many features and uses either one of
      two well-known probability density function estimation methods when computing the
      criterion. The proposed approach is compared with existing mutual information
      based methods and another sophisticated filter method on many artificial and real
      world problems. The numerical results show that the proposed method can
      effectively identify the important features in data sets having dependency among
      many features and is superior, in almost all cases, to the benchmark methods.

PMID- 22581142
TI  - A feasibility study of enhancing independent task performance for people with
      cognitive impairments through use of a handheld location-based prompting system.
AB  - An autonomous task-prompting system is presented to increase workplace and life
      independence for people with cognitive impairments such as traumatic brain
      injury, intellectual disability, schizophrenia, and Down syndrome. This paper
      describes an approach to providing distributed cognition support of work
      engagement for persons with cognitive disabilities. In the pilot study, a
      prototype was built and tested in a community-based rehabilitation program
      involving pre-service food preparation training of 8 participants with cognitive
      impairments. The results show improvement in helping with task engagement is
      statistically significant compared to the oral-instruction method. A follow-up
      comparative study with 2 participants evaluated the shadow-team approach against
      the proposed system. Although the number of participants was few, the
      participants were studied in depth and the findings were very promising. The
      results in the autonomous task prompting without staff intervention indicate that
      the performance is statistically as good as the shadow-team approach. Our
      findings suggest that acquisition of job skills may be facilitated by the
      proposed system in conjunction with operant conditioning strategies. 

PMID- 22581141
TI  - A system for seismocardiography-based identification of quiescent heart phases:
      implications for cardiac imaging.
AB  - Seismocardiography (SCG), a representation of mechanical heart motion, may more
      accurately determine periods of cardiac quiescence within a cardiac cycle than
      the electrically derived electrocardiogram (EKG) and, thus, may have implications
      for gating in cardiac computed tomography. We designed and implemented a system
      to synchronously acquire echocardiography, EKG, and SCG data. The device was used
      to study the variability between EKG and SCG and characterize the relationship
      between the mechanical and electrical activity of the heart. For each cardiac
      cycle, the feature of the SCG indicating Aortic Valve Closure was identified and
      its time position with respect to the EKG was observed. This position was found
      to vary for different heart rates and between two human subjects. A color map
      showing the magnitude of the SCG acceleration and computed velocity was derived,
      allowing for direct visualization of quiescent phases of the cardiac cycle with
      respect to heart rate.

PMID- 22581143
TI  - Superior recovery profiles of propofol-based regimen as compared to isoflurane
      based regimen in patients undergoing craniotomy for primary brain tumor excision:
      a retrospective study.
AB  - PURPOSE: Studies comparing the recovery profiles of isoflurane- and propofol
      based anesthesia for major intracranial surgery have reported contradictory
      results. The aim of our study was to clarify the emergence status in both
      regimens by investigating uniformly managed neuroanesthesia cases. METHODS: The
      anesthesia database at Yamagata University Hospital covering the period 2002-2005
      was retrospectively investigated for adult patients who underwent craniotomy for
      primary brain tumor excision. General anesthesia was provided by an isoflurane-
      (ISO group) or propofol-based (PROP group) regimen. Times to extubation and
      operating room (OR) discharge, perioperative consciousness levels, and
      perioperative variables were compared. RESULTS: Of the 202 surgeries performed
      during the study period, 77 and 82 patients were anesthetized with isoflurane and
      propofol, respectively. Demographic data were comparable between the two groups,
      although the American Society of Anesthesiology grade was worse in the PROP
      group. Extubation times [39.5 +/- 14.6 min (ISO) vs. 29.5 +/- 14.9 min (PROP); P
      < 0.001] and OR discharge times [67.2 +/- 18.0 (ISO) vs. 53.9 +/- 17.6 min
      (PROP); P < 0.001] were significantly shorter in the PROP, with significantly
      better immediate consciousness levels. The differences in levels of consciousness
      persisted for several hours postoperatively. PROP patients had significantly
      higher urine outputs and lower body temperatures during anesthesia. The
      incidences of shivering, nausea, vomiting, and convulsions were not significantly
      different between the groups. The time to discharge was similar between the
      groups. CONCLUSIONS: Propofol was associated with a better recovery profile and
      neurological condition than isoflurane, as indicated by shorter extubation and OR
      discharge times and better postoperative consciousness.

PMID- 22581144
TI  - [Minimally invasive hip arthroplasty].

PMID- 22581145
TI  - [Minimally invasive hip arthroplasty - what must be spared?].
AB  - The classical surgical approach to the hip joint has been modified in recent
      years. The development of minimally invasive surgical techniques promised a
      particularly gentle soft-tissue preparation with significant benefits in
      postoperative recovery and intraoperative blood loss for patients undergoing
      total hip arthroplasty (THA). Exact knowledge of the anatomy of the hip joint and
      the surrounding structures at risk are essential to avoid complications. Each of
      the main minimally invasive approaches for THA implicates very specific
      advantages and disadvantages. Knowing these factors, minimally invasive hip
      surgery can be performed in a soft tissue-friendly manner. The resulting
      advantages have to be checked for significant clinical evidence.

PMID- 22581146
TI  - [Nerve lesions after minimally invasive total hip arthroplasty].
AB  - Although there is no clear evidence, minimally invasive hip arthroplasty seems to
      be associated with slightly higher complication rates compared to standard
      procedures. Major nerve palsy is one of the least common but most distressing
      complications. The key for minimizing the incidence of nerve lesions is to
      analyze preoperative risk factors, accurate knowledge of the anatomy and
      minimally invasive techniques. Once clinical signs of nerve injury are evident,
      the first diagnostic steps are localization of the lesion and quantification of
      the damage pattern. Therefore, clinical assessment of the neurological deficits
      should be performed as soon as possible. Apart from rare cases of isolated
      transient conduction blockade or complete transection, the damage pattern is
      mostly combined. Thus, there can be evidence for dysfunction of nerve conduction
      (neuropraxia) and structural nerve damage (axonotmesis or neurotmesis)
      simultaneously. Because the earliest signs of denervation are detectable via
      electromyography after 1 week, it is not possible to make any reliable prognosis
      within the first days after nerve injury using electrophysiological methods. This
      review article should serve as a guideline for prevention, diagnostics and
      therapy of neural lesions in minimally invasive hip arthroplasty.

PMID- 22581147
TI  - [The minimally invasive anterolateral approach. A review of the literature].
AB  - The minimally invasive anterolateral approach for total hip arthroplasty (THA) is
      used with modifications on the basis of the Watson Jones approach and the
      approach by Hardinge. Compared to other approaches no disadvantages were found in
      the majority of studies concerning surgical time, blood loss, pain and
      complications concerning this approach. Laboratory studies described less damage
      to the gluteus muscles. These results are supported by magnetic resonance imaging
      (MRI) studies and seem to be more important in older patients. The functional
      results are partially contradictory although there are no indications of any
      disadvantages. Increased complications in the form of fractures or malpositioning
      of implants can be interpreted as a result of a learning curve. A shorter stay in
      hospital has to be interpreted in the context of the local requirements of the
      respective health service. The evaluation of minimally invasive techniques
      carried out in reviews and meta-analyses does not distinguish between different
      approaches and is based on different time periods and selection criteria. Thus,
      the conclusions drawn cannot be absolutely applied to the minimally invasive
      anterolateral approach.

PMID- 22581148
TI  - [Minimally invasive posterior approach for total hip arthroplasty].
AB  - The mini-posterior approach for total hip arthroplasty (THA) belongs to the mini
      incision approaches. In comparison to standard approaches, less muscle trauma
      resulting in less pain, less blood loss and faster rehabilitation in the early
      postoperative period are attributed to this approach, as known for all other
      minimally invasive approaches. In a prospective study of 100 cases of THA it
      could be shown that this is true when comparing the mini-posterior approach with
      the posterolateral approach. Lower levels of muscle enzymes as a parameter for
      muscle trauma, could not be seen.

PMID- 22581149
TI  - [Minimally invasive anterior approach].
AB  - The minimally invasive direct anterior approach for total hip arthroplasty (THA)
      was first published in 1985. Since then the technique has been further improved
      and the indications have been extended. The approach utilizes the muscle gap
      between the tensor fasciae latae muscle on the lateral side and the sartorius
      muscle on the medial side. This muscle gap allows a direct and quick approach to
      the hip joint with good muscle preservation. During preparation of the femur the
      tensor fasciae latae muscle is at risk of being damaged. The lateral cutaneous
      nerve of the thigh (NCFL) and its branches are also in danger of being damaged
      during skin incision and dissection of the subcutaneous tissue. In this article
      the technique, risks and current clinical results of THA using the minimally
      invasive direct anterior approach are described. The results from the literature,
      as well as own results are compared to the traditional transgluteal lateral Bauer
      approach and discussed. Reviewing the literature, special attention has been
      given to the incidence of NCFL lesions, damage of the tensor fasciae latae muscle
      and positioning of the cup. Especially for the latter, the general view is
      hindered in the minimally invasive technique.

PMID- 22581150
TI  - [Clinical results of minimally invasive total hip arthroplasty].
AB  - AIM: This article presents an analysis and review of recent literature with a
      focus on clinical results after minimally invasive (MIS) total hip arthroplasty
      (THA) and with special attention to the different approaches currently used.
      METHODS: An online database (Medline) search for clinical trials after THA
      between 2007 and 2011 was performed with a special focus on prospective
      controlled randomized trials focusing on THA with a MIS approach. The data were
      analyzed for pain, blood loss, complications, gait analysis, Harris hip and other
      scores. RESULTS: A total of 24 studies (19 comparative studies) were included in
      this study with a total of 801 MIS THA cases and 695 conventionally operated
      hips. Almost every study showed superior results for the MIS group with respect
      to postoperative pain, blood loss and rehabilitation but these advantages almost
      totally disappeared after 3-6 months. The complication rate was comparable in
      both groups. After 3-6 months the clinical scores, such as the Harris hip score
      did not show any differences between conventional and MIS groups. CONCLUSIONS: In
      this present study all MIS approaches showed advantages over the conventional
      surgical approach but these benefits disappeared after 3-6 months. With
      comparable risks for complications, MIS surgical approaches are superior in the
      early postoperative phase and rehabilitation.

PMID- 22581151
TI  - [Postoperative rehabilitation after minimally invasive total hip arthroplasty].
AB  - Currently more than 150,000 total hip arthroplasties (THA) are performed in
      Germany each year. Despite limited financial resources approximately 50% of these
      patients participate in a standardized inpatient rehabilitation program. This
      report reflects own experiences with patients after a minimally invasive approach
      for THA compared to others with conventional procedures, in context with findings
      from the literature. Rehabilitation and convalescence in patients with a
      minimally invasive approach for THA seem to have advantages especially in the
      first weeks after surgery, with manageable complications and socioeconomic
      improvements compared to conventional approaches.

PMID- 22581153
TI  - [Not Available].

PMID- 22581154
TI  - [Cell-based therapy options for osteochondral defects. Autologous mesenchymal
      stem cells compared to autologous chondrocytes].
AB  - Cartilage defects are multifactorial and site-specific and therefore need a clear
      analysis of the underlying pathology as well as an individualized therapy so that
      cartilage repair lacks a one-for-all therapy. The results of comparative clinical
      studies using cultured chondrocytes in autologous chondrocyte implantation (ACI)
      have shown some superiority over conventional microfracturing under defined
      conditions, especially for medium or large defects and in long-term durability.
      Adult mesenchymal stem cells can be isolated from bone marrow, have the potency
      to proliferate in culture and are capable of differentiating into the
      chondrogenic pathway. They represent a promising versatile cell source for
      cartilage repair but the ideal conditions for cultivation and application in
      cartilage repair are not yet known or have not yet been characterized. Adding a
      scaffold offers mechanical stability and advances chondrogenic differentiation
      for both possible cell sources.

PMID- 22581155
TI  - Millipedes that smell like bugs: (E)-alkenals in the defensive secretion of the
      julid diplopod Allajulus dicentrus.
AB  - The secretions from serial defensive glands of the Austrian diplopod Allajulus
      dicentrus (Julidae, Cylindroiulini) were extracted and analyzed by means of gas
      chromatography - mass spectrometry. In adults, 13 components from two chemical
      classes were detected: 1) The common juliform benzoquinones were represented by
      four compounds (2-hydroxy-3-methyl-1,4-benzoquinone, 2-methoxy-3-methyl-1,4
      benzoquinone, 2,3-dimethoxy-1,4-benzoquinone, and 2,3-dimethoxy-5-methyl-1,4
      benzoquinone). From this series, 2-methoxy-3-methyl-1,4-benzoquinone was most
      abundant, comprising about 40 % of the whole secretion. 2) All remaining
      compounds were identified as aliphatic (E)-alkenals [(E)-2-heptenal, (E)-2
      octenal, (E)-2-nonenal, (E)-2-decenal)] along with their corresponding alcohols.
      (E)-2-Octenal was most abundant, roughly accounting for another 35 % of the
      secretion. In juveniles, different stages in the ontogenetic development of the
      secretion were observed, with early instars (stadium III and IV) exclusively
      containing the benzoquinone fraction. Alkenols and alkenals were added in later
      instars (stadium V and VI), with secretions of stadium VI-juveniles being already
      similar to those of adults. Representatives of Spirostreptida, Spirobolida, and
      Julida traditionally have been considered to produce benzoquinonic secretions
      only ("quinone millipedes"), and information on secretion components from other
      chemical classes is still scarce. We here provide evidence for the participation
      of non-quinonic compounds in the defensive exudates of the Cylindroiulini. The
      occurrence of additional, non-quinonic compounds in certain species within a
      chemically homogenous, benzoquinone-producing taxon indicates the rapid adoption
      of novel exocrine compounds, possibly in order to meet the demands in a changed
      ecological environment.

PMID- 22581156
TI  - Renal protective effects of extracts from guava fruit (Psidium guajava L.) in
      diabetic mice.
AB  - This study analyzed the content of phenolic acids and flavonoids in extracts of
      guava fruit (Psidium guajava L.), and examined the renal protective effects of
      guava aqueous extract (GAE) and ethanol extract (GEE) in diabetic mice. GAE had
      more caffeic acid, myricetin, and quercetin; and GEE had more cinnamic, coumaric
      and ferulic acids. GAE or GEE at 1 and 2 % was supplied in diet for 12 weeks. GAE
      or GEE intake at 2 % significantly reduced glucose and blood urea nitrogen
      levels, increased insulin level in plasma of diabetic mice (p < 0.05). GAE or GEE
      treatments dose-dependently reserved glutathione content, retained activity of
      catalase and glutathione peroxidase, and decreased reactive oxygen species,
      interleukin (IL)-6, tumor necrosis factor-alpha and IL-1beta levels in kidney (p
      < 0.05). GAE and GEE treatments at 2 % significantly declined renal N (epsilon)
      (carboxymethyl)lysine, pentosidine and fructose levels (p < 0.05), and suppressed
      renal activity of aldose reductase (p < 0.05). These findings support that guava
      fruit could protect kidney against diabetic progression via its anti-oxidative,
      anti-inflammatory and anti-glycative effects.

PMID- 22581157
TI  - Dialectical behavior therapy compared with general psychiatric management for
      borderline personality disorder: clinical outcomes and functioning over a 2-year
      follow-up.
AB  - OBJECTIVE: The authors conducted a 2-year prospective naturalistic follow-up
      study to evaluate posttreatment clinical outcomes in outpatients who were
      randomly selected to receive 1 year of either dialectical behavior therapy or
      general psychiatric management for borderline personality disorder. METHOD:
      Patients were assessed by blind raters 6, 12, 18, and 24 months after treatment.
      The clinical effectiveness of treatment was assessed on measures of suicidal and
      nonsuicidal self-injurious behaviors, health care utilization, general symptom
      distress, depression, anger, quality of life, social adjustment, borderline
      psychopathology, and diagnostic status. The authors conducted between-group
      comparisons using generalized estimating equation, mixed-effects models, or chi
      square statistics, depending on the distribution and nature of the data. RESULTS:
      Both treatment groups showed similar and statistically significant improvements
      on the majority of outcomes 2 years after discharge. The original effects of
      treatment did not diminish for any outcome domain, including suicidal and
      nonsuicidal self-injurious behaviors. Further improvements were seen on measures
      of depression, interpersonal functioning, and anger. However, even though two
      thirds of the participants achieved diagnostic remission and significant
      increases in quality of life, 53% were neither employed nor in school, and 39%
      were receiving psychiatric disability support after 36 months. CONCLUSIONS: One
      year of either dialectical behavior therapy or general psychiatric management was
      associated with long-lasting positive effects across a broad range of outcomes.
      Despite the benefits of these specific treatments, one important finding that
      replicates previous research is that participants continued to exhibit high
      levels of functional impairment. The effectiveness of adjunctive rehabilitation
      strategies to improve general functioning deserves additional study.

PMID- 22581158
TI  - Mechanism(s) of alteration of micro RNA expressions in Huntington's disease and
      their possible contributions to the observed cellular and molecular dysfunctions
      in the disease.
AB  - To identify the mechanism of deregulation of micro RNAs (miRNAs) altered in
      Huntington's disease (HD) and their possible contributions to the altered
      cellular and molecular functions observed in the disease, we analyzed the altered
      miRNAs in the postmortem brains of HD patients. There are 54 miRNAs
      differentially expressed in HD brains of which 30 are upregulated and 24
      downregulated. Some of these miRNAs were also altered in various models of the
      disease. Regulation of these miRNAs was attributed to transcription factors and
      the host genes to which these miRNAs reside. We observed that transcription
      regulators TP53, E2F1, REST, and GATA4 together could regulate expressions of 26
      miRNAs in HD. Altered expressions of 13 intronic miRNAs were correlated with the
      expressions of their host genes. From literature, we further collected 287
      experimentally validated targets of miRNAs upregulated in HD, while 304 validated
      targets of downregulated miRNAs in HD. Analysis of these validated target genes
      of altered miRNAs by gene ontology (GO) revealed that these genes are
      significantly enriched in GO terms belonging to (1) apoptosis, (2)
      differentiation and development, (3) fatty acid, cholesterol, lipid, glucose, and
      carbohydrate metabolism, (4) cell cycle and growth, and (5) transcription
      regulation. Experimental evidences that these processes are altered in HD are
      provided from published reports. In conclusion, altered miRNAs in HD might target
      many genes and may contribute to the altered cellular and molecular functions
      observed in HD.

PMID- 22581159
TI  - Surgical management of the N0 neck in early stage T1-2 oral cancer; a personal
      perspective of early and late impalpable disease.
AB  - INTRODUCTION: The management of the N0 neck in early stage oral cancer remains
      controversial. The evidence in the literature for elective neck dissection, which
      is reviewed in this paper, is conflicting. My personal view is that most papers
      mistakenly assume that the N0 equates to an "early stage" neck whereas a neck
      with palpable nodes represents disease at a "late" stage. DISCUSSION: I believe
      that this is the same mindset that prevented us from realizing that depth rather
      than size was the important prognostic determinant for the primary tumor; because
      the T stage was based on tumor size. The N stage is also based on size and number
      of nodes and by these criteria N0 would be the earliest stage. However, although
      an N0 neck with impalpable intra-nodal disease may be regarded as early
      impalpable disease an N0 neck with microscopic extra-capsular spread (ECS) would
      be "late/advanced" impalpable disease. Likewise, a clinically positive neck with
      intra-nodal disease still represents early disease compared to a clinically
      positive neck with ECS. CONCLUSION: The lack of trials and studies stratifying NO
      and N +ve necks into early and late disease and comparing outcomes between these
      cohorts may explain the lack of clear-cut evidence regarding the role for
      elective neck dissection.

PMID- 22581160
TI  - Ipsilateral, isolated amaurosis after inferior alveolar nerve block: report of
      two rare cases.
AB  - BACKGROUND: Local anesthetics are utilized all over the world for performing
      painless dental procedures. Usually, the administration of local anesthetic is an
      uncomplicated process that passes off uneventfully. Complications, when seen, are
      not usually serious. However, blindness is an alarming complication both for the
      patient and for the dentist. Amaurosis can occur with both maxillary and
      mandibular nerve blocks. Amaurosis is usually associated with other ocular
      complications like ptosis, diplopia, and periorbital blanching. CASE REPORT: We
      report two rare cases of transient isolated amaurosis. Both the instances of
      amaurosis were seen after inferior alveolar nerve blocks. The condition was
      transient and resolved without any active intervention. DISCUSSION: Though
      permanent amaurosis has been reported, it is usually transient in nature. Various
      causes have been proposed like intravascular injection, sympathetic impulse
      generation, and embolism. The etiology in the present case was believed to be
      intravascular injection.

PMID- 22581161
TI  - Odontoma associated with calcifying cystic odontogenic tumor in deciduous
      dentition: case report.
AB  - BACKGROUND: Initially described by Gorlin et al. in 1962, the calcifying cystic
      odontogenic tumor (CCOT) may be associated with unerupted teeth, ameloblastomas,
      adenomatoid odontogenic tumors, and, in many cases, with odontomas. It is rare in
      patients in the first decade of life, particularly involving deciduous teeth.
      Surgery is the treatment of choice, with low recurrence rates. CASE REPORT: We
      present a clinical case of CCOT associated with odontoma and a missing deciduous
      tooth in a 3-year-old female patient. The lesion was removed under general
      anesthesia. The patient has been followed up for 1 year, and no recurrence was
      found. This appears to be the first report in such a young age.

PMID- 22581162
TI  - A graphene oxide (GO)-based molecular beacon for DNA-binding transcription factor
      detection.
AB  - A GO-based molecular beacon assay was developed for rapid, sensitive and cost
      efficient detection of transcription factor proteins. Furthermore, this assay can
      be employed for screening inhibitors of transcription factor proteins.

PMID- 22581163
TI  - Interventional closure of paravalvular leakage after transcatheter aortic valve
      implantation.

PMID- 22581164
TI  - Pseudo-mitral regurgitation 20 years after mitral valve replacement: a subannular
      left ventricular pseudoaneurysm with rupture into the left atrium.

PMID- 22581165
TI  - Imaging proliferation of 18F-FLT PET/CT correlated with the expression of
      microvessel density of tumour tissue in non-small-cell lung cancer.
AB  - PURPOSE: The aim of this study was to analyse the correlation between (18)F
      labelled 3'-deoxy-3'-fluorothymidine ((18)F-FLT) PET/CT proliferation images and
      tumour angiogenesis as reflected by intratumoral microvessel density (MVD) in non
      small-cell lung cancer (NSCLC) to provide a noninvasive method to predict the
      response to antiangiogenic therapy. METHODS: A total of 68 patients with proven
      or suspected NSCLC underwent FLT PET/CT scans followed by surgery. PET/CT images
      were compared with pathology. Tumour proliferation was evaluated in terms of a Ki
      67 labelling index (Ki-67 LI). MVD was determined using an anti-CD31 mAb (CD31
      MVD), anti-CD34 mAb (CD34-MVD) and an anti-CD105 mAb (CD105-MVD) for each
      resected tumour. RESULTS: Tumour FLT maximum standardized uptake values (SUVmax)
      were significantly correlated with the Ki-67 LI and CD105-MVD (r = 0.550 and
      0.633, P = 0.000 and 0.000, respectively), but were only marginally correlated
      with the CD31-MVD and CD34-MVD (r = 0.228 and 0.235, P = 0.062 and 0.054,
      respectively). The FLT PET false-negative patients had a longer median survival
      time than the FLT PET true-positive patients (log rank test, P = 0.012). The
      patients with a lower CD105-MVD had a longer median survival time than those with
      a higher CD105-MVD (P = 0.046), while patients with a lower CD31-MVD and CD34-MVD
      did not have a longer median survival time than those with a higher value (P =
      0.438 and 0.187, respectively). CONCLUSION: FLT PET/CT imaging correlated with
      tumour angiogenesis as reflected by CD105-MVD and prognosis, and may be helpful
      in assessing antiangiogenic therapy of NSCLC.

PMID- 22581166
TI  - Risk stratification and timing of revascularization: which patients benefit from
      early versus later revascularization?
AB  - In acute coronary syndromes, risk stratification is essential, particularly in
      patients without ST elevation, and is based upon clinical, electrocardiogram
      (ECG), and biological markers. Among them, recent and repeated attacks of angina,
      ST-segment deviation from baseline on the admission ECG as well as elevated
      markers of myonecrosis (particularly increased troponin levels), myocardial
      dysfunction (B-type natriuretic peptide [BNP]; N-terminal prohormone of BNP[NT
      proBNP]), and inflammation (high-sensitivity C-reactive protein) are predictors
      of an adverse outcome. These variables can be incorporated into broader risk
      predictive scores, among which the TIMI (Thrombolysis in Myocardial Infarction)
      and GRACE (Global Registry of Acute Coronary Events) scores are the most widely
      used. Two general therapeutic strategies (routine invasive vs conservative or
      selective invasive) are employed in the treatment of non-ST-segment elevation
      acute coronary syndrome (NSTEACS). Evidence-based analysis and the current
      American College of Cardiology/American Heart Association/Society for Cardiac
      Angiography and Interventions clinical practice guidelines recommend an early
      invasive treatment strategy (8-24 h) for intermediate or high clinical risk
      patients with NSTEACS.

PMID- 22581168
TI  - Effect of two cleaning processes for bone allografts on gentamicin impregnation
      and in vitro antibiotic release.
AB  - Bone allografts are a useful and sometimes indispensable tool for the surgeon to
      repair bone defects. Microbial contamination is a major reason for discarding
      allografts from bone banks. To improve the number of safe allografts, we suggest
      chemical cleaning of the grafts followed by antibiotic impregnation. Comparison
      of two chemical cleaning processes for bone allografts aiming for antibiotic
      impregnation and consequently delivery rates in vitro. Bone chips of 5-10 mm were
      prepared from human femoral heads. Two cleaning methods (cleaning A and cleaning
      B) based on solutions containing hydrogen peroxide, paracetic acid, ethanol and
      biological detergent were carried out and compared. After the cleaning processes,
      the bone chips were impregnated with gentamicin. Bacillus subtilis bioassay was
      used to determine the gentamicin release after intervals of 1-7 days. Differences
      were compared with non-parametric Mann-Whitney U tests. The zones of inhibition
      obtained from the bone grafts cleaned with both cleaning processes were similar
      between the groups. The concentration of the released antibiotic was decreasing
      gradually over time, following a similar pattern for both groups. The cleaning
      procedure A as well as the cleaning procedure B for bone allografts allowed the
      impregnation with gentamicin powder in the same concentrations in both groups.
      The delivery of gentamicin was similar for both groups. Both cleaning procedures
      were easy to be carried out, making them suitable for routine use at the bone
      banks.

PMID- 22581167
TI  - Coronary stent choice in patients with acute myocardial infarction.
AB  - A prompt reperfusion with primary percutaneous coronary intervention represents
      the current gold standard treatment for patients with acute myocardial
      infarction. In this setting, coronary stents have been shown to improve outcomes
      compared to plain angioplasty and are routinely used. However, the stent
      selection among patients with acute myocardial infarction is still a matter of
      some debate. An increased risk of very late (>1-year) stent thrombosis has been
      associated with the use of early-generation drug-eluting stents (DES), leading to
      concerns regarding the long-term safety of these devices. Newer-generation DES
      were developed with the aim of addressing this safety issue, and were recently
      investigated in a few randomized studies in patients with acute myocardial
      infarction. The objective of the present review is to summarize the accumulated
      evidence, to guide the stent selection in patients with acute myocardial
      infarction.

PMID- 22581169
TI  - Origin of the inhibitory activity of 4-O-substituted sialic derivatives of human
      parainfluenza virus.
AB  - Human parainfluenza virus (hPIV) is a serious human pathogen causing upper and
      lower respiratory tract disease, yet there are no effective vaccines or therapies
      to control parainfluenza virus infections. Recently, we found that 4-O
      substituted sialic derivatives have potent inhibitory activity against hPIV-1,
      whereas the anti-influenza inhibitor Zanamivir was less inhibitory. To elucidate
      the origin of the high potency inhibitory activities of these 4-O-substituted
      derivatives, we performed correlated fragment molecular orbital (FMO)
      interfragment interaction energy (IFIE) analysis for hemagglutinin-neuraminidase
      (HN) glycoprotein complexes of hPIV with the derivatives and compared them with
      those for Zanamivir. We found key interactions between the inhibitors and the
      hPIV HN glycoprotein and identified important factors for the inhibitory
      activity. These theoretical results will be useful for the development of novel
      anti-hPIV drugs.

PMID- 22581170
TI  - ZGDHu-1 promotes apoptosis of chronic lymphocytic leukemia cells.
AB  - Chronic lymphocytic leukemia (CLL) is a low-grade lymphoid malignancy incurable
      with conventional modalities of chemotherapy. We aimed to examine the
      proapoptotic effects of a novel proteasome inhibitor, N,N'-di-(m-methylphenyi)
      3,6- dimethyl-1,4-dihydro-1,2,4,5-tetrazine-1,4-dicarboamide (ZGDHu-1), on CLL
      cells. B lymphocytes were isolated from CLL patients and normal healthy controls,
      and treated with various concentrations of ZGDHu-1 for different days. CLL cell
      viability was detected by MTT assay. The apoptosis, mitochondrial membrane
      potential (?psim) and reactive oxidative species (ROS) were examined by flow
      cytometry. The expression of caspase-3 and Bcl-2/Bax ratio was detected by
      western blotting. ZGDHu-1 significantly reduced the viability of CLL cells and
      induced apoptosis in comparison to the control cells (both P<0.05). Normal
      peripheral B cells were resistant to the apoptosis-inducing effects of ZGDHu-1.
      Apoptosis induced by ZGDHu-1 was accompanied with generation of ROS, loss of
      ?psim, downregulation of Bcl-2 and increase of caspase-3 cleavage. Results of
      this study indicate that ZGDHu-1 is a promising specific treatment for CLL in the
      clinic.

PMID- 22581171
TI  - Brachytelephalangic chondrodysplasia punctata:  a case series to further
      delineate the phenotype.
AB  - Chondrodysplasia punctata (CDP) is a heterogenous group of skeletal dysplasias
      characterized by aberrant bone mineralization, manifesting radiologically as
      epiphyseal stippling. Among this group, brachytelephalangic dysplasia, a benign
      form of CDP (CDPX1), is probably under-reported. It is an X-linked recessive
      disorder and is characterized by a flat nasal tip, short columella and maxillary
      hypoplasia, involvement of terminal phalanges, and stippled chondrodystrophy.
      This paper presents a clinical series of 13 patients with brachytelephalangic
      dysplasia. These patients enrolled during 2002-2006 were re-evaluated and their
      dysmorphic features were compiled in a predesigned proforma. Skeletal survey,
      karyotype, cardiac evaluation, and ophthalmic evaluation were planned for all the
      cases. Out of 13 patients, 10 were males and three were females. All patients had
      flat facies, a depressed nasal bridge, a hypoplastic nose, a short philtrum,
      notched alae nasi, brachydactyly, and hypoplastic terminal phalanges. In
      addition, congenital heart disease, optic nerve hypoplasia, and developmental
      delay were found in a few patients. Radiography showed hypoplastic terminal
      phalanges, delayed bone age (1/13), epiphyseal stippling in carpal (3/13) and
      tarsal bones (2/13), sacral bone (1/13), and bullet-shaped lumbar vertebra
      (1/13). Cranial neuroimaging, thyroid profile, and karyotype carried out in a few
      were normal. The present paper discusses various clinical features and associated
      abnormalities in patients with brachytelephalangic dysplasia (CDPX1) to further
      delineate the phenotype. The presence of a similar phenotype in females suggests
      the possibility of another locus or manifestation of disease in heterozygous
      females. Arylsulfatase E gene analysis would further help in establishing the
      genotype-phenotype correlation.

PMID- 22581172
TI  - Extracorporeal membrane oxygenation promotes survival in children with trauma
      related respiratory failure.
AB  - Extracorporeal membrane oxygenation (ECMO), which is used for cardiopulmonary
      support in many non-trauma settings, may also be of use in pediatric patients
      with traumatic lung injury by allowing the lung to rest and heal. We have
      utilized ECMO to support three multitrauma pediatric patients with posttraumatic
      respiratory failure in the past 2 years. We sought to review our experience at a
      level 1 tertiary care children's hospital in this patient population. Our
      outcomes along with the limited number of pediatric trauma patients previously
      reported in the literature suggest that ECMO may be safely and effectively used
      to manage respiratory failure in this patient population.

PMID- 22581173
TI  - Correlation between corpus callosum shape and cognitive performance in healthy
      young adults.
AB  - Corpus callosum (CC) might be related to cognitive performance because of its
      role in interhemispheric communication. Previous research has focused mainly on
      volumetric analyses of the CC, yielding contradictory results to some extent.
      Shape is an approach that integrates and extends the data obtained with the
      volumetric methodology. Here, we analyze the relationships between midsagittal CC
      shape variation and several cognitive measures. 2D coordinates from 102 MRI
      scanned young adult human CCs were superimposed through a Procrustes approach.
      The residual variation was regressed onto 21 cognitive measures completed by the
      participants. Most of these measures (including general intelligence, working
      memory, executive functioning, and mental speed) were unrelated to midsagittal CC
      morphology. However, attentional control did show consistent and significant
      correlations with CC shape variation. Slower responses in attentional control
      were systematically associated with more curved and thinner CC, with consequent
      rotation of the splenium and the genu. Although the magnitude of the correlations
      suggests a small relationship of midsagittal CC geometry and attention, the
      results provide interesting clues regarding the links between brain anatomical
      configuration and human cognitive function.

PMID- 22581174
TI  - Fast and sensitive mapping of bisulfite-treated sequencing data.
AB  - MOTIVATION: Cytosine DNA methylation is one of the major epigenetic modifications
      and influences gene expression, developmental processes, X-chromosome
      inactivation, and genomic imprinting. Aberrant methylation is furthermore known
      to be associated with several diseases including cancer. The gold standard to
      determine DNA methylation on genome-wide scales is 'bisulfite sequencing': DNA
      fragments are treated with sodium bisulfite resulting in the conversion of
      unmethylated cytosines into uracils, whereas methylated cytosines remain
      unchanged. The resulting sequencing reads thus exhibit asymmetric bisulfite
      related mismatches and suffer from an effective reduction of the alphabet size in
      the unmethylated regions, rendering the mapping of bisulfite sequencing reads
      computationally much more demanding. As a consequence, currently available read
      mapping software often fails to achieve high sensitivity and in many cases
      requires unrealistic computational resources to cope with large real-life
      datasets. RESULTS: In this study, we present a seed-based approach based on
      enhanced suffix arrays in conjunction with Myers bit-vector algorithm to
      efficiently extend seeds to optimal semi-global alignments while allowing for
      bisulfite-related substitutions. It outperforms most current approaches in terms
      of sensitivity and performs time-competitive in mapping hundreds of millions of
      sequencing reads to vertebrate genomes. AVAILABILITY: The software segemehl is
      freely available at http://www.bioinf.uni-leipzig.de/Software/segemehl.

PMID- 22581175
TI  - Robustness and accuracy of functional modules in integrated network analysis.
AB  - MOTIVATION: High-throughput molecular data provide a wealth of information that
      can be integrated into network analysis. Several approaches exist that identify
      functional modules in the context of integrated biological networks. The
      objective of this study is 2-fold: first, to assess the accuracy and variability
      of identified modules and second, to develop an algorithm for deriving highly
      robust and accurate solutions. RESULTS: In a comparative simulation study
      accuracy and robustness of the proposed and established methodologies are
      validated, considering various sources of variation in the data. To assess this
      variation, we propose a jackknife resampling procedure resulting in an ensemble
      of optimal modules. A consensus approach summarizes the ensemble into one final
      module containing maximally robust nodes and edges. The resulting consensus
      module identifies and visualizes robust and variable regions by assigning support
      values to nodes and edges. Finally, the proposed approach is exemplified on two
      large gene expression studies: diffuse large B-cell lymphoma and acute
      lymphoblastic leukemia.

PMID- 22581176
TI  - Software support for SBGN maps: SBGN-ML and LibSBGN.
AB  - MOTIVATION: LibSBGN is a software library for reading, writing and manipulating
      Systems Biology Graphical Notation (SBGN) maps stored using the recently
      developed SBGN-ML file format. The library (available in C++ and Java) makes it
      easy for developers to add SBGN support to their tools, whereas the file format
      facilitates the exchange of maps between compatible software applications. The
      library also supports validation of maps, which simplifies the task of ensuring
      compliance with the detailed SBGN specifications. With this effort we hope to
      increase the adoption of SBGN in bioinformatics tools, ultimately enabling more
      researchers to visualize biological knowledge in a precise and unambiguous
      manner. AVAILABILITY AND IMPLEMENTATION: Milestone 2 was released in December
      2011. Source code, example files and binaries are freely available under the
      terms of either the LGPL v2.1+ or Apache v2.0 open source licenses from
      http://libsbgn.sourceforge.net. CONTACT: sbgn-libsbgn@lists.sourceforge.net.

PMID- 22581177
TI  - Exhaustive database searching for amino acid mutations in proteomes.
AB  - MOTIVATION: Amino acid mutations in proteins can be found by searching tandem
      mass spectra acquired in shotgun proteomics experiments against protein sequences
      predicted from genomes. Traditionally, unconstrained searches for amino acid
      mutations have been accomplished by using a sequence tagging approach that
      combines de novo sequencing with database searching. However, this approach is
      limited by the performance of de novo sequencing. RESULTS: The Sipros algorithm
      v2.0 was developed to perform unconstrained database searching using high
      resolution tandem mass spectra by exhaustively enumerating all single non
      isobaric mutations for every residue in a protein database. The performance of
      Sipros for amino acid mutation identification exceeded that of an established
      sequence tagging algorithm, Inspect, based on benchmarking results from a
      Rhodopseudomonas palustris proteomics dataset. To demonstrate the viability of
      the algorithm for meta-proteomics, Sipros was used to identify amino acid
      mutations in a natural microbial community in acid mine drainage. AVAILABILITY:
      The Sipros algorithm is freely available at?newline
      http://code.google.com/p/sipros.

PMID- 22581178
TI  - iFad: an integrative factor analysis model for drug-pathway association
      inference.
AB  - MOTIVATION: Pathway-based drug discovery considers the therapeutic effects of
      compounds in the global physiological environment. This approach has been gaining
      popularity in recent years because the target pathways and mechanism of action
      for many compounds are still unknown, and there are also some unexpected off
      target effects. Therefore, the inference of drug-pathway associations is a
      crucial step to fully realize the potential of system-based pharmacological
      research. Transcriptome data offer valuable information on drug-pathway targets
      because the pathway activities may be reflected through gene expression levels.
      Hence, it is of great interest to jointly analyze the drug sensitivity and gene
      expression data from the same set of samples to investigate the gene-pathway-drug
      pathway associations. RESULTS: We have developed iFad, a Bayesian sparse factor
      analysis model to jointly analyze the paired gene expression and drug sensitivity
      datasets measured across the same panel of samples. The model enables direct
      incorporation of prior knowledge regarding gene-pathway and/or drug-pathway
      associations to aid the discovery of new association relationships. We use a
      collapsed Gibbs sampling algorithm for inference. Satisfactory performance of the
      proposed model was found for both simulated datasets and real data collected on
      the NCI-60 cell lines. Our results suggest that iFad is a promising approach for
      the identification of drug targets. This model also provides a general
      statistical framework for pathway-based integrative analysis of other types of 
      omics data. AVAILABILITY: The R package 'iFad' and real NCI-60 dataset used are
      available at http://bioinformatics.med.yale.edu/group.

PMID- 22581179
TI  - Strelka: accurate somatic small-variant calling from sequenced tumor-normal
      sample pairs.
AB  - MOTIVATION: Whole genome and exome sequencing of matched tumor-normal sample
      pairs is becoming routine in cancer research. The consequent increased demand for
      somatic variant analysis of paired samples requires methods specialized to model
      this problem so as to sensitively call variants at any practical level of tumor
      impurity. RESULTS: We describe Strelka, a method for somatic SNV and small indel
      detection from sequencing data of matched tumor-normal samples. The method uses a
      novel Bayesian approach which represents continuous allele frequencies for both
      tumor and normal samples, while leveraging the expected genotype structure of the
      normal. This is achieved by representing the normal sample as a mixture of
      germline variation with noise, and representing the tumor sample as a mixture of
      the normal sample with somatic variation. A natural consequence of the model
      structure is that sensitivity can be maintained at high tumor impurity without
      requiring purity estimates. We demonstrate that the method has superior accuracy
      and sensitivity on impure samples compared with approaches based on either
      diploid genotype likelihoods or general allele-frequency tests. AVAILABILITY: The
      Strelka workflow source code is available at ftp://strelka@ftp.illumina.com/.
      CONTACT: csaunders@illumina.com

PMID- 22581180
TI  - Anonymous nuclear loci in non-model organisms: making the most of high-throughput
      genome surveys.
AB  - MOTIVATION: When working with non-model organisms, few if any species-specific
      markers are available for phylogenetic, phylogeographic and population studies.
      Therefore, researchers often try to adapt markers developed in distantly related
      taxa, resulting in poor amplification and ascertainment bias in their target
      taxa. Markers can be developed de novo and anonymous nuclear loci (ANL) are
      proving to be a boon for researchers seeking large numbers of fast-evolving,
      independent loci. However, the development of ANL can be laboratory intensive and
      expensive. A workflow is described to identify suitable low-copy anonymous loci
      from high-throughput shotgun sequences, dramatically reducing the cost and time
      required to develop these markers and produce robust multilocus datasets.
      RESULTS: By successively removing repetitive and evolutionary conserved sequences
      from low coverage shotgun libraries, we were able to isolate thousands of
      potential ANL. Empirical testing of loci developed from two reptile taxa
      confirmed that our methodology yields markers with comparable amplification rates
      and nucleotide diversities to ANLs developed using other methodologies. Our
      approach capitalizes on next-generation sequencing technologies to enable the
      development of phylogenetic, phylogeographic and population markers for taxa
      lacking suitable genomic resources.

PMID- 22581181
TI  - SRMA: an R package for resequencing array data analysis.
AB  - Sequencing by hybridization to oligonucleotides has evolved into an inexpensive,
      reliable and fast technology for targeted sequencing. Hundreds of human genes can
      now be sequenced within a day using a single hybridization to a resequencing
      microarray. However, several issues inherent to these arrays (e.g. cross
      hybridization, variable probe/target affinity) cause sequencing errors and have
      prevented more widespread applications. We developed an R package for
      resequencing microarray data analysis that integrates a novel statistical
      algorithm, sequence robust multi-array analysis (SRMA), for rare variant
      detection with high sensitivity (false negative rate, FNR 5%) and accuracy (false
      positive rate, FPR 1*10-5). The SRMA package consists of five modules for quality
      control, data normalization, single array analysis, multi-array analysis and
      output analysis. The entire workflow is efficient and identifies rare DNA single
      nucleotide variations and structural changes such as gene deletions with high
      accuracy and sensitivity. AVAILABILITY: http://cran.r-project.org/,
      http://odin.mdacc.tmc.edu/~wwang7/SRMAIndex.html

PMID- 22581182
TI  - Angiotensin II type 1 receptor (AT-1R) expression correlates with VEGF-A and VEGF
      D expression in invasive ductal breast cancer.
AB  - Recent studies point to the involvement of angiotensin II (Ang II) receptor type
      1 (AT-1R) on processes of metastasing, stimulation of invasiveness and
      angiogenesis in tumours. In this study, the correlation between intensity of AT
      1R expression and expression of lymph- and angiogenesis markers in invasive
      ductal breast cancers (IDC) was examined. Immunohistochemical studies (IHC) were
      performed on archival material of 102 IDC cases. Only 28 (27.5%) cases manifested
      low AT-1R expression while 74 (72.5%) cases demonstrated a moderate or pronounced
      AT-1R expression. Expression intensity of AT-1R was found to correlate with
      expressions of VEGF-A (r = 0.26; p = 0.008) and VEGF-D (r = 0.24; p = 0.015). Out
      of the examined markers of angiogenesis and lymphangiogenesis only the pronounced
      expression of VEGF-C was found to correlate with patient poor clinical outcome (p
      = 0.009). The positive correlation between AT-1R and VEGF-A and VEGF-D could
      point to stimulatory action of Ang II on their expression what might result in
      augmented lymph- and angiogenesis in IDC.

PMID- 22581184
TI  - Nonlinear analysis of macaque V1 color tuning reveals cardinal directions for
      cortical color processing.
AB  - Understanding color vision requires knowing how signals from the three classes of
      cone photoreceptor are combined in the cortex. We recorded from individual
      neurons in the primary visual cortex (V1) of awake monkeys while an automated,
      closed-loop system identified stimuli that differed in cone contrast but evoked
      the same response. We found that isoresponse surfaces for half the neurons were
      planar, which is consistent with linear processing. The remaining isoresponse
      surfaces were nonplanar. Some were cup-shaped, indicating sensitivity to only a
      narrow region of color space. Others were ellipsoidal, indicating sensitivity to
      all color directions. The major and minor axes of these nonplanar surfaces were
      often aligned to a set of three color directions that were previously identified
      in perceptual experiments. These results suggest that many V1 neurons combine
      cone signals nonlinearly and provide a new framework in which to decipher color
      processing in V1.

PMID- 22581183
TI  - Activation of adult-born neurons facilitates learning and memory.
AB  - Thousand of local interneurons reach the olfactory bulb of adult rodents every
      day, but the functional effect of this process remains elusive. By selectively
      expressing channelrhodopsin in postnatal-born mouse neurons, we found that their
      activation accelerated difficult odor discrimination learning and improved
      memory. This amelioration was seen when photoactivation occurred simultaneously
      with odor presentation, but not when odor delivery lagged by 500 ms. In addition,
      learning was facilitated when light flashes were delivered at 40 Hz, but not at
      10 Hz. Both in vitro and in vivo electrophysiological recordings of mitral cells
      revealed that 40-Hz stimuli produced enhanced GABAergic inhibition compared with
      10-Hz stimulation. Facilitation of learning occurred specifically when
      photoactivated neurons were generated during adulthood. Taken together, our
      results demonstrate an immediate causal relationship between the activity of
      adult-born neurons and the function of the olfactory bulb circuit.

PMID- 22581186
TI  - Experimental determination of the effective point of measurement for cylindrical
      ionization chambers in 60Co gamma radiation.
AB  - The displacement effect of cylindrical ionization chambers is taken into account
      either by an effective point of measurement (EPOM) or, alternatively, by using a
      displacement perturbation factor. The dependence of these effects in water was
      examined as a function of the cavity radius using cylindrical chambers with
      different radii and a plane-parallel chamber, whose EPOM is well known. Depth
      dose curves were measured in terms of absolute absorbed dose in water and
      evaluated according to the international protocol IAEA TRS-398 as well as the
      German protocol DIN 6800-2. As expected, evaluation of absorbed dose under
      reference conditions following both protocols agreed well within a standard
      uncertainty of 0.1%. However, values of absorbed dose at depths beyond the dose
      maximum showed deviations up to 0.3% and 0.5% for IAEA TRS-398 and DIN 6800-2,
      respectively. Values in the build-up and maximum region did not agree very well.
      Deviations of more than 1% were found for both protocols. It was concluded that
      the corrections recommended in both protocols are not fully appropriate. A
      procedure is suggested to measure the absorbed depth-dose distribution including
      the build-up region with an improved accuracy by means of cylindrical chambers.

PMID- 22581185
TI  - Channel properties reveal differential expression of TARPed and TARPless AMPARs
      in stargazer neurons.
AB  - Dynamic regulation of calcium-permeable AMPA receptors (CP-AMPARs) is important
      for normal synaptic transmission, plasticity and pathological changes. Although
      the involvement of transmembrane AMPAR regulatory proteins (TARPs) in trafficking
      of calcium-impermeable AMPARs (CI-AMPARs) has been extensively studied, their
      role in the surface expression and function of CP-AMPARs remains unclear. We
      examined AMPAR-mediated currents in cerebellar stellate cells from stargazer
      mice, which lack the prototypical TARP stargazin (g-2). We found a marked
      increase in the contribution of CP-AMPARs to synaptic responses, indicating that,
      unlike CI-AMPARs, these can localize at synapses in the absence of g-2. In
      contrast with CP-AMPARs in extrasynaptic regions, synaptic CP-AMPARs displayed an
      unexpectedly low channel conductance and strong block by intracellular spermine,
      suggesting that they were 'TARPless'. As a proof of principle that TARP
      association is not an absolute requirement for AMPAR clustering at synapses,
      miniature excitatory postsynaptic currents mediated by TARPless AMPARs were
      readily detected in stargazer granule cells following knockdown of their only
      other TARP, g-7.

PMID- 22581188
TI  - 31P-magnetic resonance spectra of ovarian cancer cells exposed to chemotherapy
      within a three-dimensional Matrigel construct.
AB  - We aimed to determine the metabolic profile and effects of chemotherapy on
      ovarian cancer cell metabolism in a three-dimensional (3D) vs. a two-dimensional
      (2D) construct using 31P-magnetic resonance spectroscopy (MRS). Three ovarian
      cancer cell lines were embedded in a 3D perfused Matrigel construct or grown in a
      2D monolayer. Metabolic differences between the three cell lines were determined
      using 31P-MRS both in the 3D and in the 2D constructs. Cells were incubated with
      three different cytotoxic drugs at LC50 for 44 h and evaluated for metabolic
      changes using 31P-MRS. While the 3D construct allowed MRS assessment of viable
      cells, the 2D monolayer permitted evaluation of non-viable cell extracts. In both
      cells embedded in Matrigel (CEM) and cells grown in monolayers (CGM) different
      cancer cell lines showed characteristic metabolic fingerprints, which differed
      significantly between CEM and CGM. In contrast to the cell monolayer, CEM allowed
      continuous monitoring of the changes in 31P-MRS spectra over time following
      exposure to chemotherapy, demonstrating a progressive decrease in specific
      phosphorylated metabolites. The metabolic response of CEM and CGM to various
      antimitotic agents was significantly different. We conclude that different
      ovarian cancer cell lines show characteristic 31P-MRS fingerprints and specific
      metabolic changes in response to cytotoxic drug treatment. The perfused 3D
      Matrigel construct is superior to the 2D tissue monolayer for 31P-MRS studies,
      because it simulates the in vivo conditions more closely and facilitates MRS
      evaluation of viable cells as well as continuous monitoring of metabolic changes
      in response to chemotherapy over time.

PMID- 22581187
TI  - Validation of criterion-based patient assignment and treatment effectiveness of a
      multidisciplinary modularized managed care program for headache.
AB  - This prospective observational study evaluates the validity of an algorithm for
      assigning patients to a multidisciplinary modularized managed care headache
      treatment program. N = 545 chronic headache sufferers [migraine (53.8 %),
      migraine + tension type (30.1 %), tension type (8.3 %) or medication overuse
      headache (6.2 %), other primary headaches (1.5 %)] were assigned to one of four
      treatment modules differing with regard to the number and types of interventions
      entailed (e.g., medication, psychological intervention, physical therapy, etc.).
      A rather simple assignment algorithm based on headache frequency, medication use
      and psychiatric comorbidity was used. Patients in the different modules were
      compared with regard to the experienced burden of disease. 1-year follow-up
      outcome data are reported (N = 160). Headache frequency and analgesic consumption
      differed significantly among patients in the modules. Headache-related disability
      was highest in patients with high headache frequency with/without medication
      overuse or psychiatric comorbidity (modules 2/3) compared to patients with low
      headache frequency and medication (module 0). Physical functioning was lowest in
      patients with chronic headache regardless of additional problems (modules 1/2/3).
      Psychological functioning was lowest in patients with severe chronicity
      with/without additional problems (module 2/3) compared to headache suffers with
      no/moderate chronicity (module 0/1). Anxiety or depression was highest in
      patients with severe chronicity. In 1-year follow-up, headache frequency (minus
      45.3 %), consumption of attack-aborting drugs (minus 71.4 %) and headache-related
      disability decreased (minus 35.9 %). Our results demonstrate the clinical
      effectiveness and the criterion validity of the treatment assignment algorithm
      based on headache frequency, medication use and psychiatric comorbidity.

PMID- 22581189
TI  - Treatment strategies for severe C1C2 luxation due to congenital os odontoideum
      causing tetraplegia.
AB  - PURPOSE: High-grade C1C2 luxation is a rare pathology. There is no clear evidence
      as to how to treat this deformity. There is only limited evidence about the
      different surgical techniques and possible approaches including advantages,
      disadvantages, and complications. METHODS: This is an uncommon case of a 13-year
      old child with progressive, tetraplegia due to congenital os odontoideum with
      translational instability between C1 and C2, and progressive luxation of C2. An
      irreducible dislocation of the C0/C1 complex caused significant compression at
      the cervicomedullary junction and neurologic deficit. In this paper we highlight
      the different types of os odontoideum, a review of existing evidence of surgical
      correction. We will discuss the different treatment strategies which could be
      applied and the current solution will be described. RESULTS: Continuous skeletal
      traction and translational reduction was achieved by a specially designed halo
      traction system including continuous skeletal traction in a wheelchair for 6
      weeks. The surgical treatment consisted of a posterior only release,
      translational reduction and posterior instrumentation from C0 to C4 with a Y
      plate and homologous bone graft. Neurological deficits started to improve during
      halo traction. After surgery the patient was ambulatory without any assistance
      and reached a Frankel stage E. Postoperative X-rays and CT scan revealed complete
      reduction at the C1/C2 level and a decompressed cervicomedullary junction.
      CONCLUSION: Treatment of severe C1C2 luxation is difficult with limited evidence
      in the literature. The current case shows a successful treatment strategy to
      reduce the deformity and lists alternative approaches.

PMID- 22581190
TI  - Drug therapy in spinal tuberculosis.
AB  - Although the discovery of effective anti-tuberculosis drugs has made
      uncomplicated spinal tuberculosis a medical disease, the advent of multi-drug
      resistant Mycobacterium tuberculosis and the co-infection of HIV with
      tuberculosis have led to a resurgence of the disease recently. The principles of
      drug treatment of spinal tuberculosis are derived from our experience in treating
      pulmonary tuberculosis. Spinal tuberculosis is classified to be a severe form of
      extrapulmonary tuberculosis and hence is included in Category I of the WHO
      classification. The tuberculosis bacilli isolated from patients are of four
      different types with different growth kinetics and metabolic characteristics.
      Hence multiple drugs, which act on the different groups of the mycobacteria, are
      included in each anti-tuberculosis drug regimen. Prolonged and uninterrupted
      chemotherapy (which may be 'short course' and 'intermittent' but preferably
      'directly observed') is effective in controlling the infection. Spinal Multi-drug
      resistant TB and spinal TB in HIV-positive patients present unique problems in
      management and have much poorer prognosis. Failure of chemotherapy and emergence
      of drug resistance are frequent due to the failure of compliance hence all
      efforts must be made to improve patient compliance to the prescribed drug
      regimen. 

PMID- 22581191
TI  - Reviewer's comment concerning "The influence of preoperative MRI findings on
      lumbar fusion clinical outcomes" (doi:10.1007/s00586-012-2244-9 Mladen
      Djurasovic, Leah Y. Carreon, Charles H. Crawford III, Jason Zook, Kelly Bratcher,
      Steven D. Glassman).

PMID- 22581192
TI  - Primary spinal cord tumors: review of 678 surgically treated patients in Japan. A
      multicenter study.
AB  - PURPOSE: To clarify the relative frequency of various histopathological primary
      spinal cord tumors and their features in Japanese people and to compare this data
      with other reports. METHODS: Primary spinal cord tumor surgical cases from 2000
      to 2009, which were registered in our affiliated hospital database were
      collected. We examined age at surgery, sex, anatomical location, vertebral level
      of the tumor, and pathological diagnosis in each case. RESULTS: Of the 678
      patients in our study, 377 patients (55.6 %) were males and 301 patients (44.4 %)
      were females (male/female ratio 1.25). The mean age at surgery was 52.4 years. Of
      these tumors, 123 cases (18.1 %) were intramedullary, 371 cases (54.7 %) were
      intradural extramedullary, 28 cases (4.1 %) were epidural, and 155 cases (22.9 %)
      were dumbbell tumors. The pathological diagnoses included 388 schwannomas (57.2
      %), 79 meningiomas (11.6 %), 54 ependymomas (8.0 %), 27 hemangiomas (4.0 %), 23
      hemangioblastomas (3.4 %), 23 neurofibromas (3.4 %), and 9 astrocytomas (1.3 %).
      The male/female ratios for schwannomas, meningiomas, ependymomas, hemangiomas,
      hemangioblastomas, neurofibromas, malignant lymphomas, and lipomas are 1.4, 0.34,
      1.3, 1.5, 2.3, 1.3, 2.7 and 2.3, respectively. CONCLUSION: This is the first
      published research in English on the epidemiology of primary spinal cord tumors
      in Japanese people. Similar to other reports from Asian countries, our data
      indicates a higher male/female ratio overall for spinal cord tumors, a higher
      proportion of nerve sheath cell tumors, and a lower proportion of meningiomas and
      neuroepithelial tumors compared to reports from non-Asian countries. Data in the
      current study represent the characteristics of primary spinal cord tumors in
      Asian countries.

PMID- 22581193
TI  - Does adding heavy load eccentric training to rehabilitation of patients with
      unilateral subacromial impingement result in better outcome? A randomized,
      clinical trial.
AB  - PURPOSE: To investigate superior value of adding heavy load eccentric training to
      conservative treatment in patients with subacromial impingement. METHODS: Sixty
      one patients with subacromial impingement were included and randomly allocated to
      the traditional rotator cuff training (TT) group (n = 30, mean age = 39.4 +/-
      13.1 years) or traditional rotator training combined with heavy load eccentric
      training (TT + ET) group (n = 31, mean age = 40.2 +/- 12.9 years). Isometric
      strength was measured to abduction at 0 degrees , 45 degrees  and 90 degrees  of
      scapular abduction and to internal and external rotation. The SPADI questionnaire
      was used to measure shoulder pain and function. Patients rated subjective
      perception of improvement. Outcome was assessed at baseline, at 6 and 12 weeks
      after start of the intervention. Both groups received 9 physiotherapy treatments
      over 12 weeks. At home, the TT group performed traditional rotator cuff
      strengthening exercises 1x/day. The TT + ET group performed the same exercises
      1x/day and a heavy load eccentric exercise 2x/day. RESULTS: After treatment,
      isometric strength had significantly increased in all directions, and SPADI score
      had significantly decreased. The TT + ET group showed a 15% higher gain in
      abduction strength at 90 degrees  of scapular abduction. Chi-square tests showed
      patients' self-rated perception of improvement was similar in both groups.
      CONCLUSION: Adding heavy load eccentric training resulted in a higher gain in
      isometric strength at 90 degrees  of scapular abduction, but was not superior for
      decreasing pain and improving shoulder function. This study showed that the
      combination of a limited amount of physiotherapy sessions combined with a daily
      home exercise programme is highly effective in patients with impingement. LEVEL
      OF EVIDENCE: II.

PMID- 22581194
TI  - Assessment of functional performance after anterior cruciate ligament
      reconstruction: a systematic review of measurement procedures.
AB  - PURPOSE: The purpose of this systematic review was to identify the measurements
      that are used in clinical practice to assess the quantity and quality of
      functional performance in men and women more than 2 years after ACL
      reconstruction with bone patellar-tendon bone (BPTB) or semitendinosus/gracilis
      (STG) graft. METHODS: A systematic literature search was performed in Medline
      (Pubmed), EMBASE (OVID), the Cochrane Library and PEDro to identify relevant
      articles from 1990 up to 2010. Articles were included if they described
      functional performance after BPTB or STG reconstruction and had a follow-up of
      more than 2 years. Two authors screened the selected articles for title, abstract
      and full-text in accordance with predefined inclusion and exclusion criteria. The
      methodological quality of all articles was assessed by checklists of the Cochrane
      Library by two authors. Only the articles with good methodological quality were
      considered for further analysis. RESULTS: A total of 27 studies were included by
      full-text. According to their methodological quality six were rated as good.
      Different authors used different study designs for muscle testing which led to
      different outcomes that could not be compared. Besides strength, a single-leg hop
      for distance was used as a measurement for quantity of functional performance. No
      measurements for quality of functional performance were reported. CONCLUSIONS:
      Measurement of functional performance more than 2 years after ACL reconstruction
      consists of concentric or isometric strength, the single-leg hop for distance or
      a combination. The Limb Symmetry Index is used as the main outcome parameter to
      compare the involved leg with the uninvolved. In all studies the results of men
      and woman are combined. Based on our findings and previous studies that discussed
      additional important parameters a more extensive test battery to assess
      functional performance is suggested.

PMID- 22581195
TI  - Arthroscopic refixation of a combined fracture of the greater and lesser
      tuberosity of the proximal humerus.
AB  - Combined fractures of the greater and the lesser tuberosity are very rare
      injuries. This is a case report on arthroscopic treatment using suture anchors
      and one distal fixation screw. Clinical and radiographic follow-up showed
      recovery of active motion and consolidation of the fragments in anatomic
      positions. LEVEL OF EVIDENCE: V.

PMID- 22581196
TI  - Games and gambling involvement among casino patrons.
AB  - A growing literature is addressing the nature of the relationships among gambling
      activity, gambling involvement, and gambling-related problems. This research
      suggests that among the general population, compared to playing any specific
      game, gambling involvement is a better predictor of gambling-related problems. To
      date, researchers have not examined these relationships among casino patrons, a
      population that differs from the general population in a variety of important
      ways. A survey of 1160 casino patrons at two Las Vegas resort casinos allowed us
      to determine relationships between the games that patrons played during the 12
      months before their casino visit, the games that patrons played during their
      casino visit, and patrons' self-perceived history of gambling-related problems.
      Results indicate that playing specific gambling games onsite predicted (i.e.,
      statistically significant odds ratios ranging from .5 to 4.51) self-perceived
      gambling-related problems. However, after controlling for involvement,
      operationally defined as the number of games played during the current casino
      visit and self-reported gambling frequency during the past 12 months, the
      relationships between games and gambling-related problems disappeared or were
      attenuated (i.e., odds ratios no longer statistically significant). These results
      extend the burgeoning literature related to gambling involvement and its
      relationship to gambling-related problems.

PMID- 22581197
TI  - Professional and pathological gamblers: similarities and differences.
AB  - Although much recent research has focused on the gambling practices and
      psychosocial functioning of pathological gamblers, few investigations have
      examined the characteristics of professional gamblers. The current project sought
      to address this gap in the literature by conducting a quantitative comparison of
      professional and pathological gamblers. Pathological gamblers were recruited and
      balanced with professional gamblers on demographic variables and preferred
      gambling activity. A total of 22 professional gamblers and 13 pathological
      gamblers completed an extensive self-report battery including instruments
      assessing demographics, gambling behaviors and problems, other psychiatric
      disorders, current psychosocial functioning, recent stressful events, personality
      characteristics, and intelligence. Pathological and professional gamblers
      reported similar rates of gambling frequency and intensity and types of games
      played. Pathological gamblers endorsed poor psychosocial functioning, whereas
      professional gamblers reported a rate of psychiatric distress within a normative
      range. Pathological gamblers also reported lower gambling self-efficacy, greater
      impulsivity, and more past-year DSM-IV Axis I disorders than professional
      gamblers. The results of the present study shed light on the unique circumstances
      of professional gamblers, as well as underscore important differences between
      such individuals and pathological gamblers that could prove fruitful in future
      research and intervention and prevention efforts.

PMID- 22581198
TI  - Segmentation in low-penetration and low-involvement categories: an application to
      lottery games.
AB  - Market segmentation is accepted as a fundamental concept in marketing and several
      authors have recently proposed a segmentation model where personal and
      environmental variables intersect with each other to form motivating conditions
      that drive behavior and preferences. This model of segmentation has been applied
      to packaged goods. This paper extends this literature by proposing a segmentation
      model for low-penetration and low involvement (LP-LI) products. An application to
      the lottery games in Chile supports the proposed model. The results of the study
      show that in this type of products (LP-LI), the attitude towards the product
      category is the most important factor that distinguishes consumers from non
      consumers, and heavy users from light users, and consequently, a critical
      segmentation variable. In addition, a cluster analysis shows the existence of
      three segments: (1) the impulsive dreamers, who believe in chance, and in that
      lottery games can change their life, (2) the skeptical, that do not believe in
      chance, nor in that lottery games can change their life and (3) the willing, who
      value the benefits of playing. 

PMID- 22581199
TI  - Comparison of eligible non-enrolled patients and the randomised TWENTE trial
      population treated with Resolute and Xience V drug-eluting stents.
AB  - AIMS: The TWENTE trial recently enrolled more than 80% of all eligible patients,
      who were randomised to zotarolimus-eluting Resolute or everolimus-eluting XIENCE
      V stents. In the present study, we investigated whether eligible, non-enrolled
      patients differed from the randomised TWENTE trial population in baseline
      characteristics and one-year outcome. METHODS AND RESULTS: Characteristics of
      1,709 eligible patients were analysed. Independent external adjudication of
      clinical events was likewise performed for non-enrolled (n=318) and randomised
      patients (n=1,391). Non-enrolled and randomised patients did not differ in gender
      distribution, diabetes mellitus, and clinical presentation, but differed
      significantly in age and cardiovascular history. Nevertheless, clinical outcome
      after one year did not differ in the primary composite endpoint target-vessel
      failure (TVF; 9.8% vs. 8.1%; p=0.34), and its components cardiac death (1.6% vs.
      1.2%; p=0.61), target vessel-related myocardial infarction (4.7% vs. 4.6%;
      p=0.92), and target-vessel revascularisation (3.8% vs. 3.0%; p=0.48). Previous
      bypass surgery predicted TVF in non-enrolled patients (p=0.001); removal of these
      patients resulted in identical TVF rates for non-enrolled and randomised patients
      (7.3% vs. 7.3%; p=0.99). CONCLUSIONS: Despite some differences in baseline
      characteristics, non-enrolled and randomised patients did not differ in one-year
      outcome, which was favourable for both populations and may be related to the drug
      eluting stents used.

PMID- 22581201
TI  - A technique for placement of a bioabsorbable prosthesis with fibrin glue fixation
      for reinforcement of the crural closure during hiatal hernia repair.
AB  - INTRODUCTION: Level 1 data suggest that mesh reinforcement of the crural closure
      for hiatal hernia repair decreases the recurrence of hernia. The fear of erosion
      of the prosthetic into the esophagus has kept the use of mesh for hiatal hernia
      repair from becoming routine. A recent study found several cases of esophageal
      stenosis/erosion from the use of a biologic mesh. For these reasons, we evaluated
      a new resorptive prosthetic and new method of fixation of the prosthetic for
      crural reinforcement during hiatal hernia repair. METHODS: From February 2009
      until December 2010, 70 patients underwent hiatal hernia repair using a synthetic
      bioabsorbable prosthetic made of polglycolide and teimethylene carbonate (Gore
      BioA Tissue ReinforcementTM, Flagstaff, AZ). There were 48 patients with
      paraesophageal hiatal hernias and 22 with large sliding hiatal hernias. In this
      study, a square piece of mesh just the size to cover the crural closure only was
      utilized. Fibrin glue (TisseelTM) was applied over the suture closure of the
      crura, the mesh was then placed over the glue and held in place for several
      seconds, and then more fibrin glue was applied on top of the mesh. RESULTS: The
      new bioabsorbable polymer mesh was readily placed through a 10-mm trocar, had
      good handling characteristics laparoscopically, and no pre-operative preparation
      was required of the prosthetic. The material and the fibrin glue created a very
      substantial reinforcement of the crural closure, and the average time to place
      and fix the mesh was approximately 5 min. There were no short-term complications
      from the mesh, and no patient has had any significant post-operative sequelae.
      CONCLUSION: Crural closure reinforcement during hiatal hernia repair can be done
      readily with this new bioabsorbable polymer-based mesh. Fibrin glue fixation of
      this new prosthetic can be done quickly and it creates a strong, fixed barrier
      that may decrease the chance of erosion. Further studies will need to be done to
      evaluate long-term efficacy and complications associated with its use.

PMID- 22581200
TI  - Cortical thinning in psychopathy.
AB  - OBJECTIVE: Psychopathy is a personality disorder associated with severely
      antisocial behavior and a host of cognitive and affective deficits. The
      neuropathological basis of the disorder has not been clearly established.
      Cortical thickness is a sensitive measure of brain structure that has been used
      to identify neurobiological abnormalities in a number of psychiatric disorders.
      The authors assessed cortical thickness and corresponding functional connectivity
      in psychopathic prison inmates. METHOD: Using T1 MRI data, the authors computed
      cortical thickness maps in a sample of adult male prison inmates selected on the
      basis of psychopathy diagnosis (21 psychopathic inmates and 31 nonpsychopathic
      inmates). Using restingstate functional MRI data from a subset of these inmates
      (20 psychopathic inmates and 20 nonpsychopathic inmates), the authors then
      computed functional connectivity within networks exhibiting significant thinning
      among psychopaths. RESULTS: Relative to nonpsychopaths, psychopaths had
      significantly thinner cortex in a number of regions, including the left insula
      and dorsal anterior cingulate cortex, the left and right precentral gyri, the
      left and right anterior temporal cortices, and the right inferior frontal gyrus.
      These neurostructural differences were not due to differences in age, IQ, or
      substance use. Psychopaths also exhibited a corresponding reduction in functional
      connectivity between the left insula and the left dorsal anterior cingulate
      cortex. CONCLUSIONS: Psychopathy is associated with a distinct pattern of
      cortical thinning and reduced functional connectivity.

PMID- 22581202
TI  - Single-port hernia repair: a prospective cohort of 102 patients.
AB  - BACKGROUND: Single-port laparoscopic surgery (SPLS) for totally extraperitoneal
      (TEP) groin hernia repair is a novel procedure, ensuring safe and effective
      repairs. The aim of this study was to assess the intra-operative and post
      operative outcome for 102 patients undergoing SPLS TEP inguinal hernia repair at
      the Royal Surrey County Hospital in Guildford, UK. This follows on from our
      previously published series of 16 patients, demonstrating the safety and
      feasibility of SPLS in our cohort (Agrawal et al. in Surg Endosc 24:952-956,
      2010). METHODS: Between October 2008 and August 2010, we performed hernia repairs
      on 102 patients (98 men, 4 women) aged between 21 and 89 years (median 60).
      Patient demographics, type of hernia, incision length, operating time,
      complications, post-operative hospital stay, and recurrence were collected
      prospectively. Post-operative outcome was measured in terms of days to return to
      normal activities, work, and analgesia required. RESULTS: Sixty patients had
      unilateral and 39 bilateral hernias, with 2 femoral hernias and one lipoma of
      cord. Operating time was 15-120 min (median 35 for unilateral and 45 for
      bilateral repairs). The incision length ranged between 15 and 40 mm (median 25).
      There was 1 intra-operative complication (major peritoneal incursion) and 13
      minor post-operative complications, with 8 urinary retentions. There were no
      mortalities and one recurrence at follow-up (up to 713 days). CONCLUSION: The
      authors' experience has shown that SPLS TEP groin hernia repair is a feasible and
      safe alternative to three-port laparoscopic hernia repairs in a large patient
      cohort. There were minimal post-operative complications and good post-operative
      outcome. Recurrence rate was 0.98 %. Further studies are required to assess the
      long-term outcome of SPLS hernia repairs in direct comparison with three-port
      technique.

PMID- 22581203
TI  - COPD and osteoporosis: something more than a comorbidity.

PMID- 22581204
TI  - Androgens for postmenopausal women's health?
AB  - Obesity, metabolic syndrome, and diabetes are becoming a leading health concern
      in the developed Countries, due to their link to cardiovascular disease. These
      conditions are common in women in the post-menopausal period. Unfortunately,
      actual lifestyle change strategy fail to prevent cardiovascular events for
      several reasons, thus specific medications are needed. In addition, it was showed
      an increased cardiovascular diseases and breast cancer risk in postmenopausal
      women taking estrogens alone or with progestin, thus the optimal therapy for the
      prevention of chronic disease in women is still lacking. Androgens exert
      different actions on organs like adipose tissue, brain, bone, and on
      cardiovascular system. However, a debate still exists on the positive role of
      androgens on human health, especially in women. Furthermore, the vascular effects
      of androgens remain poorly understood and have been controversial for a long
      time. Sex hormones are important determinants of body composition. Aging is,
      often, accompanied by a decrease in free testosterone levels, a concomitant
      reduction in muscle mass and an increase in fat mass. Furthermore, numerous
      studies showed that total serum testosterone levels were inversely related to the
      atherosclerosis disease incidence in postmenopausal women. New therapeutic
      targets may, therefore, arise understanding how androgen could influence the fat
      distribution, the metabolic disease onset, the vascular reactivity and
      cardiovascular risk, in both sex.

PMID- 22581205
TI  - Diagnostic value of antithyroid peroxidase antibody for incidental autoimmune
      thyroiditis based on histopathologic results.
AB  - Detection of antithyroid peroxidase antibody (TPOAb) is widely used in the
      diagnosis of autoimmune thyroiditis (AIT), but no research has evaluated the
      diagnostic accuracy of TPOAb detection using histopathologic reference standards.
      To fill this research gap, this study assessed the diagnostic accuracy of
      detection of TPOAb and that of other serological markers in asymptomatic patients
      who had been diagnosed with AIT by histopathologic analysis after thyroid
      surgery. After review of patient records, 598 patients who had undergone thyroid
      nodule surgery were enrolled for examination for thyroid parenchyma by a
      pathologist and classification into no co-existing lymphocytic thyroiditis,
      Hashimoto thyroiditis, or non-Hashimoto type of lymphocytic thyroiditis (NHLT).
      The correlation between patient serological data and thyroid parenchyma pathology
      was analyzed. Statistically significant differences (P < 0.05) were found between
      co-existing lymphocytic thyroiditis and no co-existing lymphocytic thyroiditis
      groups regarding thyroid-stimulating hormone (TSH) and TPOAb levels. And, TPOAb
      titer was significantly associated with the degree of inflammation. An abnormal
      TPOAb titer was found in 86 of the 598 patients (14.4 %) and the specificity of
      TPOAb detection for AIT diagnosis was found to be 96.9 %. The prevalence of
      Hashimoto thyroiditis and NHLT in the 560 papillary thyroid cancer (PTC) patients
      was found to be 7.9 and 17.9 %, respectively. The results indicate that TPOAb
      titer is associated with the degree of thyroid inflammation and that detection of
      TPOAb is a very specific means of diagnosing AIT. The results also indicate that
      the incidence of AIT and PTC coexistence is relatively high.

PMID- 22581206
TI  - Corticosteroid use for diabetic macular edema: old fad or new trend?
AB  - Diabetic retinopathy is the leading cause of blindness in working age individuals
      in developed countries. Most cases of diabetes related vision loss result from
      breakdown of the blood-retinal barrier with resultant diabetic macular edema
      (DME). For over 30 years, laser photocoagulation has been the standard therapy
      for DME, but most eyes do not experience significant improvements in visual
      acuity. Intravitreal injections of drugs that inhibit the action of vascular
      endothelial growth factor (VEGF) lead to gains in vision, but can be expensive
      and need to be repeated frequently. In addition to VEGF-mediated breakdown of the
      blood-retinal barrier, recent evidence suggests that inflammation plays an
      important role in the development of DME. Recognizing this, physicians have
      injected steroids into the vitreous and developers have created sustained release
      implants. Intravitreal injections of triamcinolone acetonide lead to rapid
      resolution of macular edema and significant short-term improvements in visual
      acuity, but unfortunately, visual acuities diminish when treatment is continued
      through 2 years. However, intravitreal triamcinolone remains an attractive
      treatment option for eyes that are pseudophakic, scheduled to undergo cataract
      surgery, resistant to laser photocoagulation, or require urgent panretinal
      photocoagulation for proliferative retinopathy. In controlled trials, intraocular
      implants that slowly release dexamethasone and fluocinolone show promise in
      reducing macular edema and improving visual acuity. The high incidences of drug
      related cataracts and glaucoma, however, require that corticosteroids be used
      cautiously and that patients be selected carefully. The increasing number of
      patients with DME, the burgeoning cost of medical care and the continuing
      development of intravitreal steroids suggest that the use of these agents will
      likely increase in coming years.

PMID- 22581208
TI  - Impact of pasteurization on the antibacterial properties of human milk.
AB  - Growing evidence favours the use of human milk for the feeding of preterm
      newborns based on its many beneficial effects. Despite the many benefits, human
      milk has been associated as a possible vehicle of transmission for a number of
      infections. Although pasteurization of human milk can diminish the risk of
      neonatal infection, it also significantly reduces the concentrations of
      immunological components in human milk due to thermal damage. In order to
      evaluate the impact of pasteurization on the antibacterial properties of human
      milk, we aimed to compare the capacity of raw and pasteurized human milk to
      inhibit bacterial proliferation. Therefore, a single milk sample was collected
      from ten healthy lactating mothers. Each sample was divided into two aliquots;
      one aliquot was pasteurized, while the other was kept raw. Both aliquots were
      inoculated either with Escherichia coli or Staphylococcus aureus and incubated at
      37  degrees C during 8 h. Viable colony counts from the inoculated samples were
      performed at regular time points to compare the bacterial growth in both forms of
      breast milk. Relative to the tryptic soy broth control sample, both raw and
      pasteurized milk samples exhibited an inhibitory effect on the growth of E. coli
      and S. aureus. Compared with the raw portion, growth inhibition was significantly
      lower in the pasteurized milk at every time point beyond T0 (after 2, 4 and 8 h
      of incubation) (p = 0.0003 for E. coli and p < 0.0001 for S. aureus). CONCLUSION:
      Our study shows that pasteurization adversely affects the antibacterial
      properties of human milk.

PMID- 22581209
TI  - Microbiological spectrum of the intraperitoneal surface after elective right
      sided colon cancer: are there differences in the peritoneal contamination after
      performing a stapled or a handsewn anastomosis?
AB  - BACKGROUND: Although colonic surgery is performed with strict aseptic measures,
      some contamination is nearly impossible to avoid. In stapled anastomosis, the
      hole opened in the colon is minimum, just necessary for introducing the parts of
      the mechanical devices. In handsewn anastomosis, the colonic lumen is more
      exposed to the peritoneum, despite colonic occlusion with clamps while the suture
      is performed. PATIENTS AND METHODS: A prospective, randomized study was performed
      between October 2009 and June 2011. Inclusion criteria were a diagnosis of right
      sided colon cancer and having undergone an elective surgery with curative aims.
      The patients were divided into two groups: those patients undergoing a stapled
      ileocolonic anastomosis (group 1) and those undergoing a handsewn anastomosis
      (group 2). A microbiological sample was obtained from the peritoneal surface
      before opening the colon and after finishing the anastomosis in each group. Data
      were correlated with the wound infection and intra-abdominal infection rates.
      RESULTS: Eighty-four patients were included in the study: 42 patients in each
      group. There were two intra-abdominal abscesses (5 %) in each group (NS). Wound
      infection rate was 10 % in group 1 and 7 % in group 2 (NS). Mean operative time
      was 98.8 min in the stapled group and 105.2 min in the handsewn one (P = 0.013).
      Positive cultures were obtained in 79 % of the cases after stapled anastomosis
      and 73 % after handsewn ones (NS). CONCLUSION: Peritoneal contamination appears
      in over 70 % of cases after ileocolonic anastomosis. Significant differences in
      peritoneal contamination, wound infection, and intra-abdominal abscess between
      stapled and handsewn anastomoses could not be demonstrated.

PMID- 22581207
TI  - Prospective and parallel assessments of cystic fibrosis newborn screening
      protocols in the Czech Republic: IRT/DNA/IRT versus IRT/PAP and IRT/PAP/DNA.
AB  - Cystic fibrosis (CF) is a life-threatening disease for which early diagnosis
      following newborn screening (NBS) improves the prognosis. We performed a
      prospective assessment of the immunoreactive trypsinogen (IRT)/DNA/IRT protocol
      currently in use nationwide, versus the IRT/pancreatitis-associated protein (PAP)
      and IRT/PAP/DNA CF NBS protocols. Dried blood spots (DBS) from 106,522 Czech
      newborns were examined for IRT concentrations. In the IRT/DNA/IRT protocol, DNA
      testing was performed for IRT >= 65 ng/mL. Newborns with IRT >= 200 ng/mL and no
      detected cystic fibrosis transmembrane conductance regulator gene (CFTR)
      mutations were recalled for a repeat IRT. In the same group of newborns, for both
      parallel protocols, PAP was measured in DBS with IRT >= 50 ng/mL. In PAP-positive
      newborns (i.e., >=1.8 if IRT 50-99.9 or >=1.0 if IRT >= 100, all in ng/mL), DNA
      testing followed as part of the IRT/PAP/DNA protocol. Newborns with at least one
      CFTR mutation in the IRT/DNA/IRT and IRT/PAP/DNA protocols; a positive PAP in
      IRT/PAP; or a high repeat IRT in IRT/DNA/IRT were referred for sweat testing.
      CONCLUSION: the combined results of the utilized protocols led to the detection
      of 21 CF patients, 19 of which were identified using the IRT/DNA/IRT protocol, 16
      using IRT/PAP, and 15 using IRT/PAP/DNA. Decreased cut-offs for PAP within the
      IRT/PAP protocol would lead to higher sensitivity but would increase false
      positives. Within the IRT/PAP/DNA protocol, decreased PAP cut-offs would result
      in high sensitivity, an acceptable number of false positives, and would reduce
      the number of DNA analyses. Thus, we concluded that the IRT/PAP/DNA protocol
      would represent the most suitable protocol in our conditions.

PMID- 22581210
TI  - Association between increased tumor necrosis factor alpha levels and acquired
      activated protein C resistance in patients with metastatic colorectal cancer.
AB  - PURPOSE: The purpose of this study was to investigate the possible association
      between tumor necrosis factor-alpha (TNF-alpha) levels and defects in the
      activated protein C (APC) system as a determinant of venous thromboembolism (VTE)
      in metastatic colorectal cancer patients (mCRC) undergoing chemotherapy. METHODS:
      TNF-alpha levels (measured by immunoassay) and abnormalities in the APC system
      [evaluated by an APC-dependent thrombin generation assay (ThromboPath-ThP)] were
      evaluated in 45 mCRC patients undergoing chemotherapy. VTE events were recorded
      during follow-up. RESULTS: TNF-alpha levels were increased (p < 0.01), and APC
      functionality was decreased (p < 0.0001) in mCRC patients compared to age- and
      sex-matched controls. An inverse correlation was observed between TNF-alpha and
      APC impairment in mCRC (p < 0.0001). TNF-alpha was confirmed as an independent
      predictor (p = 0.007) for APC abnormalities at multivariate regression analysis.
      Nine (20 %) of 45 mCRC patients experienced VTE during chemotherapy. Bayesian
      analysis of combined ThP/TNF-alpha showed a positive predictive value of 0.67 in
      predicting VTE (p = 0.01). Cox proportional hazards survival analysis confirmed
      the predictive value of combined ThP/TNF-alpha determination in VTE risk
      assessment of mCRC patients (either negative vs. both positive: HR = 0.02; p =
      0.001), and Kaplan-Meier analysis demonstrated that mCRC patients with either
      negative TNF-alpha or ThP values prior to chemotherapy were less likely to
      experience VTE (13 %) than patients with abnormalities of both markers (67 %, p =
      0.002). CONCLUSIONS: These results suggest that the host inflammatory response to
      cancer cells and/or tumor-derived cytokines could be responsible for an
      impairment of the APC system and a switch toward a pro-thrombotic state, which
      might predispose to the occurrence of VTE in mCRC patients undergoing
      chemotherapy.

PMID- 22581211
TI  - Conotoxin engineering: dual pharmacophoric noradrenaline transport
      inhibitor/integrin binding peptide with improved stability.
AB  - A dual-pharmacophoric peptide was engineered by grafting the integrin binding RGD
      motif between the C- and N-termini of a disulfide-rich noradrenaline transporter
      inhibiting chi-conotoxin resulting in a stable backbone cyclized peptide. The
      construct maintained two independent biological activities and showed increased
      plasma stability with no adverse effects observed following administration to
      rats, highlighting the potential value of pharmacophore grafting into constrained
      peptide scaffolds.

PMID- 22581215
TI  - A tumor-derived population (SCCOHT-1) as cellular model for a small cell ovarian
      carcinoma of the hypercalcemic type.
AB  - The small cell ovarian carcinoma of the hypercalcemic type (SCCOHT) represents an
      aggressive tumor with poor prognosis predominantly affecting young women and so
      far, no cell line or animal model is available to investigate this devastating
      disease. Biopsy material from a recurrent SCCOHT was subjected to an explant
      culture to obtain an adherent and continuously proliferating cell population.
      Morphological and functional characterization revealed a heterogeneous population
      (SCCOHT-1) of about 13 um in diameter and approximately 36 h of doubling time.
      Flow cytometric analysis of surface markers demonstrated the expression of CD15,
      CD29, CD44 and CD90 paralleled by the presence of cytokeratins and vimentin.
      Cytogenetic analysis and high-resolution oligo-array comparative genomic
      hybridization (aCGH) demonstrated a stable karyotype including deletions of the
      PARK2, CSMD1, GRIN2B and ATF7IP genes. Following lentiviral transduction with a
      GFP vector, the labeled SCCOHT-derived cells were subjected to CCE to separate
      distinct subpopulations as evidenced by cell cycle analysis. Subcutaneous
      injection of these subpopulations into NOD/SCID mice exhibited hypercalcemia and
      a tumor development in 100% of the mice. Re-cultivation of the mouse tumors
      revealed an outgrowth of SCCOHT-derived phenotypes and all cell populations
      expressed high telomerase activity. Moreover, histopathological evaluation
      demonstrated close similarities between the mouse tumors and the original patient
      tumor. In conclusion, SCCOHT-1 cells provide a study platform to investigate this
      rare disease and to examine effective and sufficient therapeutic strategies for
      this rather unknown type of cancer.

PMID- 22581216
TI  - Predicting the risk of multiple endocrine neoplasia type 1 for patients with
      commonly occurring endocrine tumors.
AB  - OBJECTIVE: Endocrine diseases that can be part of the rare inheritable syndrome
      multiple endocrine neoplasia type 1 (MEN1) commonly occur in the general
      population. Patients at risk for MEN1, and consequently their families, must be
      identified to prevent morbidity through periodic screening for the detection and
      treatment of manifestations in an early stage. The aim of the study was to
      develop a model for predicting MEN1 in individual patients with sporadically
      occurring endocrine tumors. DESIGN: Cross-sectional study. METHODS: In a
      nationwide study in The Netherlands, patients with sporadically occurring
      endocrine tumors in whom the referring physician suspected the MEN1 syndrome were
      identified between 1998 and 2011 (n=365). Logistic regression analysis with
      internal validation using bootstrapping and external validation with a cohort
      from Sweden was used. RESULTS: A MEN1 mutation was found in 15.9% of 365
      patients. Recurrent primary hyperparathyroidism (pHPT; odds ratio (OR) 162.40);
      nonrecurrent pHPT (OR 25.78); pancreatic neuroendocrine tumors (pNETs) and
      duodenal NETs (OR 17.94); pituitary tumor (OR 4.71); NET of stomach, thymus, or
      bronchus (OR 25.84); positive family history of NET (OR 4.53); and age (OR 0.96)
      predicted MEN1. The c-statistic of the prediction model was 0.86 (95% confidence
      interval (95% CI) 0.81-0.90) in the derivation cohort and 0.77 (95% CI 0.66-0.88)
      in the validation cohort. CONCLUSION: With the prediction model, the risk of MEN1
      can be calculated in patients suspected for MEN1 with sporadically occurring
      endocrine tumors.

PMID- 22581218
TI  - Iterative image reconstruction in helical cone-beam x-ray CT using a stored
      system matrix approach.
AB  - We present a stored system matrix (SM) approach for iterative x-ray CT image
      reconstruction with helical cone-beam geometry. Because of the symmetry of a
      helical source trajectory, it is sufficient to calculate and store the SM entries
      for one transaxial slice only and for all source positions illuminating the
      slice. This is made possible by (1) selecting the reconstruction slice thickness
      to be an integer multiple of the source translation per projection view, and (2)
      discretizing the 3D reconstruction volume on a rotated stack of slices. Using the
      proposed method, the memory requirement for reconstructing a full field-of-view
      of clinical scanners is manageable on current computing platforms. The same
      storage principle can be generalized and applied to volume-of-interest (VOI)
      image reconstruction for helical cone-beam CT. In this case, the stored SM
      entries correspond to a partial- or full-ring region on one transaxial slice, and
      for all source positions illuminating the ring. The size and location of the ring
      depend on the size and the location of the VOI and the scan geometry. We
      demonstrate by both computer simulations and clinical patient data the speed and
      efficacy of iterative image reconstruction using the stored SM approach.

PMID- 22581222
TI  - Medical treatment failure and complete left pneumonectomy after Legionella
      pneumophila pneumonia in a bone marrow transplant recipient.
AB  - Legionnaire disease (LD) is infrequently considered in the differential diagnoses
      for hospital- and community-acquired pneumonia in pediatrics. We report a case of
      Legionnaire disease in a 19-year-old male with aplastic anemia after bone marrow
      transplant, who was being treated in a children's hospital. Severe, refractory
      pulmonary disease necessitated pneumonectomy to control the infection.

PMID- 22581220
TI  - Virus load kinetics and resistance development during oseltamivir treatment in
      infants and children infected with Influenza A(H1N1) 2009 and Influenza B
      viruses.
AB  - BACKGROUND: Infants and small children are the most effective transmitters of
      influenza, while bearing a high risk of hospitalization and adverse disease
      outcomes. This study aims to investigate virus load kinetics and resistance
      development during oseltamivir therapy in infants and children infected with
      influenza A(H1N1) 2009 and influenza B viruses. METHODS: Virus load in
      nasopharyngeal samples and phenotypic/genotypic neuraminidase inhibitor
      resistance were determined at baseline, at day 5 and in additional follow-up
      samples, if available. Patient-specific viral clearance indices CLnu(i) were
      determined along with estimates of the time required to achieve nondetectable
      virus load. RESULTS: No evidence of baseline oseltamivir resistance was detected
      in 36 patients infected with influenza A(H1N1) 2009 (n = 27) or influenza B
      (Victoria, Yamagata; n = 9) before oseltamivir therapy. On average, viral loads
      were lower for influenza type B (median = 5.9.10/mL) than for drug-resistant
      (median = 2.6.10/mL) and sensitive A(H1N1) 2009 (median = 4.8.10/mL), P = 0.04
      and P = 0.09, respectively. Time required to achieve nondetectable virus load was
      significantly longer in drug-resistant A(H1N1) 2009 (median 15.4 days) compared
      with drug-sensitive A(H1N1) 2009 (P = 0.003; median 7.7 days) and drug-sensitive
      influenza B (P = 0.001; median 5 days). No evidence of viral rebound was observed
      once viral clearance was achieved. CONCLUSIONS: Our data indicate that influenza
      subtyping in combination with baseline viral load measurements might help to
      optimize the duration of antiviral therapy in the individual child. Lower than
      expected virologic response rates in patients without malabsorption or compliance
      issues may suggest resistance development.

PMID- 22581217
TI  - Current management and future directions for the treatment of patients
      hospitalized for heart failure with low blood pressure.
AB  - Although patients hospitalized with heart failure have relatively low in-hospital
      mortality, the post-discharge rehospitalization and mortality rates remain high
      despite advances in treatment. Most patients admitted for heart failure have
      normal or high blood pressure, but 15-25 % have low systolic blood pressure with
      or without signs and/or symptoms of hypoperfusion. All pharmacological agents
      known to improve the prognosis of patients with heart failure also reduce blood
      pressure, and this limits their use in patients with heart failure and low blood
      pressure (HF-LBP). However, patients with HF-LBP have much higher in-hospital and
      post-discharge mortality. In these patients, a conceptually important therapeutic
      target is to improve cardiac output in order to alleviate signs of hypoperfusion.
      Accordingly, the majority of these patients will require an inotrope as cardiac
      dysfunction is the cause of their low cardiac output. However, the short-term use
      of currently available inotropes has been associated with further decreases in
      blood pressure and increases in heart rate, myocardial oxygen consumption and
      arrhythmias. Agents that improve cardiac contractility without this undesirable
      effects should be developed. To the best of our knowledge, the epidemiology,
      pathophysiology and therapy of patients with HF-LBP have not been addressed
      thoroughly. In June 2010, a workshop that included scientists and clinicians was
      held in Rome, Italy. The objectives of this meeting were to (1) develop a working
      definition for HF-LBP, (2) describe its clinical characteristics and
      pathophysiology, (3) review current therapies and their limitations, (4) discuss
      novel agents in development and (5) create a framework for the design and conduct
      of future clinical trials.

PMID- 22581223
TI  - Prospective long-term outcomes of a cohort of Ugandan children with laboratory
      monitoring during antiretroviral therapy.
AB  - BACKGROUND: Treatment of HIV-1 infected Ugandan children with antiretroviral
      therapy (ART) is increasing, but few prospective long-term studies evaluating the
      treatment process have been reported. In this study, we sought to determine
      prospectively how consistent monitoring of HIV-1 RNA levels affects the ART
      treatment process. METHODS: One hundred eight children initiating ART were
      enrolled into this study. These children had comprehensive laboratory monitoring,
      including HIV-1 RNA level determination and genotype analysis (where
      appropriate), CD4% plus absolute counts and safety laboratory measurements
      performed before starting therapy and at regular intervals after receiving ART.
      Kaplan-Meier statistics were used to examine predictors of survival and virologic
      failure. Viral genotype analysis was performed on samples obtained from children
      having virologic failure to determine the emergence of mutations. RESULTS:
      Clinically, there was no difference in the 3-year survival between our cohort
      receiving consistent laboratory monitoring and a matched historical clinic cohort
      not routinely receiving laboratory monitoring. However, 34% of children receiving
      ART demonstrated virologic failure. Eleven of these children received second-line
      ART, and all responded with an undetectable HIV-1 RNA level and an increase in
      CD4 count. Children remaining on a failing antiretroviral regimen accumulated
      resistance mutations. CONCLUSIONS: Our prospective long-term findings support the
      general use of monitoring HIV-1 RNA levels for the management of children on ART
      and the adoption of a clearer definition for virologic failure and better
      guidelines for managing children with unsuppressed HIV-1 RNA levels.

PMID- 22581224
TI  - Vaccine-derived human-bovine double reassortant rotavirus in infants with acute
      gastroenteritis.
AB  - We describe 3 cases of acute gastroenteritis in healthy infants after vaccination
      with RotaTeq, shedding a G1P[8] human-bovine double reassortant rotavirus in
      stools. Such a double reassortant virus appears stable in vitro and may explain
      diarrheal symptoms in a small percentage of RotaTeq recipients, and might also be
      transmitted to contacts in the environment.

PMID- 22581225
TI  - Risk factors of amphotericin B toxicty in the nonneonatal pediatric population.
AB  - BACKGROUND: Amphotericin B (AmB) traditionally has been the mainstay of therapy
      for children with candidemia but is associated with drug-related toxicities
      (DRT). Studies investigating the risk factors for AmB DRT in children are
      limited. METHODS: A retrospective review of patients aged 6 months to <=18 years
      with candidemia who received >=1 dose of AmB from 2003 to 2009 was conducted at
      Texas Children's Hospital, Houston, TX. Patient demographics, risk factors, drug
      dosages, laboratory adverse effects and infusion-related side effects (INFRT)
      were recorded. RESULTS: A total of 223 episodes of candidemia occurred in 179
      patients. AmB was administered in 172 (77%) episodes. Amphotericin B
      deoxycholate, Amphotericin B lipid complex and liposomal Amphotericin B were
      administered in 65 (38%), 96 (55%) and 11 (6.4%) episodes, respectively. When the
      first episode of AmB use was analyzed separately (n = 138), DRT occurred in 83%
      (n = 114); nephrotoxicity occurred in 45% (n = 62), hypokalemia in 47% (n = 62)
      and INFRT in 31 % (n = 41). The most common INFRT was chills and rigors (80%, n =
      33) followed by fever (31.7%, n = 13) and hypotension (9.7%, n = 4). Patients
      with lower baseline creatinine clearance were at increased risk of having
      nephrotoxicity than those with higher baseline creatinine clearance (P = 0.004).
      Nephrotoxicity was less likely in patients who received immunosuppressants (P =
      0.02). Neutropenia (P = 0.02) and prior hypokalemia (P = 0.001) were
      independently associated with hypokalemia. The receipt of premedication was
      independently associated with a lower likelihood of INFRT (P <= 0.0001). It is
      important to note that most AmB-related DRT was quickly reversible. CONCLUSIONS:
      AmB-associated DRT was common and reversible in our nonneonatal pediatric
      population. Prospective studies are required to further evaluate risk factors and
      determine whether they are modifiable.

PMID- 22581226
TI  - Early detection of HIV infection among Kenyan infants using a reverse
      transcriptase activity assay.
AB  - Two hundred HIV-exposed Kenyan infants were tested for HIV infection at birth and
      at age 6, 12, 24 and 48 weeks, by DNA polymerase chain reaction (PCR) and Cavidi
      reverse transcriptase (RT) assays and after age 18 months by HIV antibody test.
      Eleven (5.5%) infants became HIV infected. In 6 infants, positive RT preceded
      positive DNA PCR. The use of RT assay may facilitate earlier HIV diagnosis in
      infants.

PMID- 22581227
TI  - Drug expenditure of high-cost patients and their characteristics in Finland.
AB  - BACKGROUND: Little information exists on how constantly growing pharmaceutical
      expenditures are distributed in large representative samples of national
      populations in Western countries. OBJECTIVE: This study analyzes the distribution
      of pharmaceutical expenditures in ambulatory care and explores the basic
      characteristics of the high-cost drug users. METHOD: Reimbursed prescription drug
      purchases in 2009 were derived from the National Prescription Register for a 50%
      sample of the adult Finnish population. The high-cost users who were among the
      top 5% in terms of drug expenditures were identified based on annual drug costs.
      RESULTS: The distribution of pharmaceutical costs is strongly skewed in Finland;
      only 5% of the population accounts for about half of the costs. These high-cost
      drug users were older than the low-cost drug users, with more than one-fourth of
      them being over 75 years old. The high-cost drug users used, on average, more
      drugs than the low-cost drug users, but approximately 15% of them used only 1-5
      drugs. Almost 50% of the high-cost drug users used more than 10 drugs per year.
      They had chronic diseases more often than the low-cost drug users, especially
      uremia requiring dialysis, post-transplant conditions, severe anemia associated
      with chronic renal failure and multiple sclerosis were common among the high-cost
      users. CONCLUSION: The skewness of the cost distribution indicates a need for
      more patient-specific cost-containment methods, and the high number of drugs in
      the high-cost group calls for exploring the possibilities of disease management
      and patient monitoring techniques in cost containment.

PMID- 22581229
TI  - CCDC103 mutations cause primary ciliary dyskinesia by disrupting assembly of
      ciliary dynein arms.
AB  - Cilia are essential for fertilization, respiratory clearance, cerebrospinal fluid
      circulation and establishing laterality. Cilia motility defects cause primary
      ciliary dyskinesia (PCD, MIM244400), a disorder affecting 1:15,000-30,000 births.
      Cilia motility requires the assembly of multisubunit dynein arms that drive
      ciliary bending. Despite progress in understanding the genetic basis of PCD,
      mutations remain to be identified for several PCD-linked loci. Here we show that
      the zebrafish cilia paralysis mutant schmalhans (smh(tn222)) encodes the coiled
      coil domain containing 103 protein (Ccdc103), a foxj1a-regulated gene product.
      Screening 146 unrelated PCD families identified individuals in six families with
      reduced outer dynein arms who carried mutations in CCDC103. Dynein arm assembly
      in smh mutant zebrafish was rescued by wild-type but not mutant human CCDC103.
      Chlamydomonas Ccdc103/Pr46b functions as a tightly bound, axoneme-associated
      protein. These results identify Ccdc103 as a dynein arm attachment factor that
      causes primary ciliary dyskinesia when mutated.

PMID- 22581230
TI  - Mutations in IRX5 impair craniofacial development and germ cell migration via
      SDF1.
AB  - Using homozygosity mapping and locus resequencing, we found that alterations in
      the homeodomain of the IRX5 transcription factor cause a recessive congenital
      disorder affecting face, brain, blood, heart, bone and gonad development. We
      found through in vivo modeling in Xenopus laevis embryos that Irx5 modulates the
      migration of progenitor cell populations in branchial arches and gonads by
      repressing Sdf1. We further found that transcriptional control by Irx5 is
      modulated by direct protein-protein interaction with two GATA zinc-finger
      proteins, GATA3 and TRPS1; disruptions of these proteins also cause craniofacial
      dysmorphisms. Our findings suggest that IRX proteins integrate combinatorial
      transcriptional inputs to regulate key signaling molecules involved in the
      ontogeny of multiple organs during embryogenesis and homeostasis.

PMID- 22581231
TI  - Parallel domestication of the Shattering1 genes in cereals.
AB  - A key step during crop domestication is the loss of seed shattering. Here, we
      show that seed shattering in sorghum is controlled by a single gene, Shattering1
      (Sh1), which encodes a YABBY transcription factor. Domesticated sorghums harbor
      three different mutations at the Sh1 locus. Variants at regulatory sites in the
      promoter and intronic regions lead to a low level of expression, a 2.2-kb
      deletion causes a truncated transcript that lacks exons 2 and 3, and a GT-to-GG
      splice-site variant in the intron 4 results in removal of the exon 4. The
      distributions of these non-shattering haplotypes among sorghum landraces suggest
      three independent origins. The function of the rice ortholog (OsSh1) was
      subsequently validated with a shattering-resistant mutant, and two maize
      orthologs (ZmSh1-1 and ZmSh1-5.1+ZmSh1-5.2) were verified with a large mapping
      population. Our results indicate that Sh1 genes for seed shattering were under
      parallel selection during sorghum, rice and maize domestication.

PMID- 22581232
TI  - Plasticity and banking potential of cultured adipose tissue derived mesenchymal
      stem cells.
AB  - The present day research on stem cells is yet not filled to the gunwales. The
      correlation of stem cell technology with tissue repair still has a long way to
      go. Since Embryonic stem cells are a kind of thorn inside when it comes to
      therapeutics, there emerged few potent contemporary sources of stem cells. Though
      bone marrow proves to be the pioneer among these, they lose themselves to adipose
      tissue in various aspects. The major shortcoming of bone marrow lies in lieu of
      its loss in potency with age. Adipose tissue puts up a tough competition among
      leading edge stem cell sources like cord blood and cord matrix. Adipose tissue
      wins over its counterparts in that it possesses astounding proliferation potency
      in vitro and holds a prominent stand in showcasing in vivo tissue repair
      efficacy. In spite of its precedence, the whole enchilada of adipose derived stem
      cells is still in its salad days. In our work we aim at excogitating the
      Mesenchymal stem cell population present in cultured adipose derived stem cells,
      in a wide perspective. Furthermore, the coalition of cell adhesion molecules with
      the proliferation potency of MSC and analysis of growth curve of ADSC was also
      paid accolade. The presence of robust MSC with immense differentiation and
      transdifferentiation potency was endorsed by lucrative differentiation of P3
      cells into mesodermal and neuronal lineages. Additionally, mesenchymal stem cells
      exhibiting coherent expression of surface markers at P3 in all samples can be
      cryopreserved for therapeutic applications.

PMID- 22581233
TI  - Therapeutic targeting of oncogenic transforming growth factor-beta1 signaling by
      antisense oligonucleotides in oral squamous cell carcinoma.
AB  - The transforming growth factor-beta1 (TGF-beta1) signaling pathway is important
      in human oral squamous cell carcinoma (OSCC). Accordingly, the aims of this study
      were to evaluate the effect of antisense TGF-beta1 oligonucleotides (ODNs) on
      OSCC in cell culture and in a xenograft model, as well as to evaluate any effects
      ODNs have on proliferating cell nuclear antigen (PCNA) and matrix
      metalloproteinase-2 (MMP-2) expression in the xenograft model. We performed real
      time cell electronic sensing (RT-CES) to determine the effect of antisense TGF
      beta1 ODNs on SCC-9 cell growth. To examine the in vivo effect of antisense TGF
      beta1 ODN therapy, SCC-9 cells were grafted into nude mice. Antisense ODNs were
      injected into the mass daily. Tumor size, body weight and duration of survival
      were assessed daily. Specimens from the main mass were used for
      immunohistochemical staining to analyze PCNA and MMP-2 expression. In vitro
      treatment with antisense TGF-beta1 ODNs decreased TGF-beta1 expression and growth
      of SCC-9 cells. In the xenograft model, the antisense TGF-beta1 ODN group
      exhibited a significantly decreased tumor growth rate compared to the control,
      which received Dulbecco's modified Eagle's medium (DMEM) (P=0.022). However, mean
      survival time and body weights were not significantly different between the
      groups (P>0.05). Immunohistochemistry showed that tumors from animals that
      received antisense TGF-beta1 ODNs had significantly lower expression levels of
      PCNA and MMP-2 compared to tumors from animals in the DMEM group (P<0.05). In
      conclusion, antisense TGF-beta1 ODN therapy significantly inhibits tumor growth
      compared to controls, however, there are no significant differences between
      groups with respect to changes in body weight.

PMID- 22581234
TI  - Dual-energy CT of the urinary tract.
AB  - With the ability to provide structural- and material-specific information with
      single phase of image acquisition, dual-energy CT has several useful applications
      in urinary tract imaging such as evaluation of renal mass, CT urography, and
      characterization of urinary calculi. Although the underlying principle of dual
      energy scanning is similar, there are several important differences in the
      currently available dual-energy scanners and the image processing algorithms used
      for these scanners. Knowledge of the principle of dual-energy data acquisition
      and image processing is essential to understand the advantages and limitations of
      dual-energy CT in urinary tract imaging.

PMID- 22581235
TI  - CT of gallbladder cancer and its mimics: a pattern-based approach.
AB  - On computed tomography (CT), gallbladder pathology may be detected incidentally
      or as the etiology of symptoms that prompted imaging. Accurate pathologic
      diagnosis can be challenging, however, due to overlapping appearances of
      malignant and benign gallbladder disease. This pictorial essay takes a pattern
      based approach to CT of the gallbladder, to help the radiologist formulate the
      proper differential diagnosis.

PMID- 22581236
TI  - Examining transcranial direct-current stimulation (tDCS) as a treatment for
      hallucinations in schizophrenia.
AB  - OBJECTIVE: Some 25%-30% of patients with schizophrenia have auditory verbal
      hallucinations that are refractory to antipsychotic drugs. Outcomes in studies of
      repetitive transcranial magnetic stimulation suggest the possibility that
      application of transcranial direct-current stimulation (tDCS) with inhibitory
      stimulation over the left temporo-parietal cortex and excitatory stimulation over
      the left dorsolateral prefrontal cortex could affect hallucinations and negative
      symptoms, respectively. The authors investigated the efficacy of tDCS in reducing
      the severity of auditory verbal hallucinations as well as negative symptoms.
      METHOD: Thirty patients with schizophrenia and medication-refractory auditory
      verbal hallucinations were randomly allocated to receive 20 minutes of active 2
      mA tDCS or sham stimulation twice a day on 5 consecutive weekdays. The anode was
      placed over the left dorsolateral prefrontal cortex and the cathode over the left
      temporo-parietal cortex. RESULTS: Auditory verbal hallucinations were robustly
      reduced by tDCS relative to sham stimulation, with a mean diminution of 31%
      (SD=14; d=1.58, 95% CI=0.76-2.40). The beneficial effect on hallucinations lasted
      for up to 3 months. The authors also observed an amelioration with tDCS of other
      symptoms as measured by the Positive and Negative Syndrome Scale (d=0.98, 95%
      CI=0.22-1.73), especially for the negative and positive dimensions. No effect was
      observed on the dimensions of disorganization or grandiosity/excitement.
      CONCLUSIONS: Although this study is limited by the small sample size, the results
      show promise for treating refractory auditory verbal hallucinations and other
      selected manifestations of schizophrenia.

PMID- 22581237
TI  - Clinical relevance of occult stress urinary incontinence (OSUI) following vaginal
      prolapse surgery: long-term follow-up.
AB  - INTRODUCTION AND HYPOTHESIS: Patients with genital prolapse and occult stress
      urinary incontinence (OSUI) are typically treated with prolapse surgery and anti
      incontinence surgery based on either a one-step approach or a two-step approach.
      The aim of our study was to determine whether anti-incontinence surgery is
      necessary based on the occurrence of OSUI in a study cohort with a long follow-up
      period. METHODS: Prolapse surgery was performed using a vaginal approach.
      Preoperatively, a stress test, a pad test and an assessment of the urodynamics
      were performed with and without prolapse reduction. Over a follow-up period of 2
      8 years, the patients with preoperative evidence of OSUI underwent
      urogynaecological examinations, stress tests and pad tests. RESULTS: Of 113
      patients with preoperative evidence of OSUI, 57 (50.4 %) were followed up for an
      average of 5.7 years (range 2-8) after prolapse surgery. Of 57 patients, 16 (28.1
      %) had objective and/or subjective stress urinary incontinence (SUI) during the
      follow-up period, but only 3 patients (5.3 %) required subsequent tension-free
      vaginal tape (TVT) surgery. In 17 of 57 patients (29.8 %), prolapse recurred.
      CONCLUSIONS: Despite the preoperative evidence of OSUI, the manifestation of SUI
      rarely occurs, with 28.1 % of patients experiencing SUI over long-term follow-up
      after vaginal prolapse surgery. Anti-incontinence surgery was necessary in only
      three cases (5.3 %). These results indicate that with the one-step approach, 54
      of 57 patients (94.7 %) would have received prophylactic anti-incontinence
      surgery unnecessarily. In conclusion, we recommend the two-step approach in the
      management of vaginal prolapse surgery in patients with OSUI.

PMID- 22581228
TI  - A genome-wide approach accounting for body mass index identifies genetic variants
      influencing fasting glycemic traits and insulin resistance.
AB  - Recent genome-wide association studies have described many loci implicated in
      type 2 diabetes (T2D) pathophysiology and beta-cell dysfunction but have
      contributed little to the understanding of the genetic basis of insulin
      resistance. We hypothesized that genes implicated in insulin resistance pathways
      might be uncovered by accounting for differences in body mass index (BMI) and
      potential interactions between BMI and genetic variants. We applied a joint meta
      analysis approach to test associations with fasting insulin and glucose on a
      genome-wide scale. We present six previously unknown loci associated with fasting
      insulin at P < 5 * 10(-8) in combined discovery and follow-up analyses of 52
      studies comprising up to 96,496 non-diabetic individuals. Risk variants were
      associated with higher triglyceride and lower high-density lipoprotein (HDL)
      cholesterol levels, suggesting a role for these loci in insulin resistance
      pathways. The discovery of these loci will aid further characterization of the
      role of insulin resistance in T2D pathophysiology.

PMID- 22581238
TI  - Sexual function following outside-in transobturator midurethral sling procedures:
      a prospective study.
AB  - INTRODUCTION AND HYPOTHESIS: Midurethral tapes have shown favorable clinical
      outcomes for treating stress urinary incontinence (SUI), but the effects of
      outside-in transobturator midurethral sling procedures (TOT) on women's sexual
      function are unclear. We hypothesized that TOT might improve sexual function in
      women with SUI and therefore conducted this study to investigate sexual function
      alteration among women who underwent TOT for urodynamic stress incontinence
      (USI). METHODS: From November 2009 to October 2010, we recruited 102 women
      scheduled for correction of USI by TOT procedures in a tertiary hospital. In
      addition to urogynecologic history, pelvic examination, and urodynamic testing,
      participants were required to complete three validated questionnaires:
      Incontinence Impact Questionnaire (IIQ-7), Urogenital Distress Inventory (UDI-6),
      and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12).
      Preoperative and postoperative results of these validated questionnaires were
      evaluated. RESULTS: Eighty-three patients comprising 57 sexually active and 26
      sexually inactive patients participated in the 12-month evaluation. Of the 83
      patients undergoing TOT, six (7.2 %) had postoperative SUI 12 months
      postoperatively. Both UDI-6 and IIQ-7 scores were significantly improved
      postoperatively. The total PISQ-12 score did not change significantly after
      surgery. Postoperatively, the individual incontinence-related items of the PISQ
      12 improved, but climax with intercourse and negative emotional reactions during
      intercourse worsened (both with p <0.001). There was a negative correlation
      between SUI-related items on UDI-6 and those on PISQ-12 preoperatively.
      CONCLUSIONS: TOT procedures for correcting USI had favorable clinical outcomes
      and did not alter overall sexual function; however, climax during sexual
      intercourse and emotional response worsened postoperatively.

PMID- 22581239
TI  - Vaginal incisional wound healing in a rabbit menopause model: a histologic
      analysis.
AB  - INTODUCTION AND HYPOTHESIS: The vaginal wound healing process is a major
      determinant of surgical outcome following pelvic reconstructive surgery. Since
      the majority of these surgeries are performed in peri- and postmenopausal women,
      it is essential to understand how estrogen deficiency affects this process. We
      aimed to histologically evaluate the vaginal incisional wound healing process in
      a rabbit menopause model. METHODS: Sixty three rabbits were utilized and divided
      into 3 groups: Twenty one underwent bilateral oophorectomy, 21 underwent a sham
      surgery, and 21 served as controls. Eight weeks later, standardized full
      thickness 6 mm circular segments were excised from the vagina of all rabbits and
      spontaneous healing was recorded. Animals were euthanized sequentially, before
      wounding, and at 0, 4, 7, 14, 21 and 35 days after wounding, and their wounds
      were harvested and assessed histologically for wound healing using a validated
      scoring system. RESULTS: Oophorectomized rabbits showed significantly delayed
      wound closure (p < 0.02), neovascularization (p < 0.01), granulation tissue
      accumulation and maturation (p < 0.02), collagen deposition (p < 0.01) and re
      epithelialization (p < 0.01), however acute and chronic inflammation were
      significantly enhanced (p < 0.02). CONCLUSION: Oophorectomized rabbits show
      protracted incisional vaginal wound healing by all histologic criteria, however,
      inflammation is significantly enhanced.

PMID- 22581240
TI  - Vaginal reconstruction with sigmoid colon in patients with congenital absence of
      vagina and menses retention: a report of treatment experience in 22 young women.
AB  - INTRODUCTION AND HYPOTHESIS: We evaluated the surgical feasibility, sexual
      satisfaction and complications of vaginal reconstruction with sigmoid colon in
      patients with congenital absence of vagina and menses retention. METHODS:
      Retrospective analysis of surgical techniques and long-term postoperative follow
      up was performed for 22 patients who underwent vaginal reconstruction with
      sigmoid colon at a single hospital between 1977 and 2011 to treat congenital
      absence of vagina with menses retention. RESULTS: All patients achieved
      satisfactory sexual function after marriage. No patients experienced
      enterospastic abdominal pain during sexual intercourse. The neovaginas
      accommodated two or more fingers and had depths >10 cm. The mucous membranes were
      soft and flexible, and secretions of the sigmoid mucosa provided adequate and
      acceptable lubrication. No patient required vaginal stents, and none developed
      vaginal stenosis or reported pain with vaginal expansion. Fifteen of the 22
      patients underwent hysterectomies due to cervical agenesis; seven retained their
      uterus and had onset of normal menses postoperatively. Two patients became
      pregnant 1 year after marriage; one achieved 38-week gestation, underwent
      cesarean section due to premature rupture of membranes, and delivered a healthy
      boy. The other experienced natural incomplete abortion and underwent curettage at
      her local hospital. CONCLUSION: This study confirms that sigmoid colon vaginal
      reconstruction is a good choice for treating congenital absence of vagina and
      menses retention and results in the closest approximation to the physical
      function of a normal female vagina. Reproductive ability can be retained in many
      cases for patients with a well-developed uterus and cervix.

PMID- 22581243
TI  - "Don't worry, it's just poker!"--experience, self-rumination and self-reflection
      as determinants of decision-making in on-line poker.
AB  - On-line poker is a game of chance and skill. The construct of poker playing skill
      has both a technical (game strategy-related) and an emotional (emotion regulation
      related) aspect. A correlational on-line study (N = 354) was conducted to assess
      differences in technical skills and emotional characteristics related to poker
      playing style between experienced and inexperienced poker players. Results
      suggest that, with respect to emotional characteristics, experienced poker
      players engage in less self-rumination and more self-reflection, as compared to
      inexperienced players. Experienced poker players are also able to make better
      decisions, by mathematical standards, in a poker decision-making environment, as
      assessed by two fictitious on-line poker decision-making scenarios. Furthermore,
      this study provides supportive evidence that experienced poker players
      conceptualize the construct of "luck" differently from inexperienced players. A
      new poker playing experience scale (PES) for accurately measuring poker playing
      experience is presented in this paper.

PMID- 22581241
TI  - Diagnosing pubovisceral avulsions: a systematic review of the clinical relevance
      of a prevalent anatomical defect.
AB  - The aims of this systematic literature review were to assess whether the
      detection of pubovisceral avulsions using magnetic resonance (MR) imaging or
      perineal ultrasonography was clinically relevant in women with pelvic floor
      dysfunction and to evaluate the relation with anatomy, symptoms, and recurrence
      after surgery. We performed a systematic literature review using three
      bibliographical databases (PubMed, Embase, and CINAHL) as data sources. Clinical
      studies were included in which pubovisceral avulsions were studied in relation to
      pelvic organ prolapse (POP) stage, pelvic floor symptoms, and/or recurrence of
      POP after surgery. Ultimately, 21 studies met the inclusion criteria. POP stage
      and recurrence of POP after surgery were strongly associated with pubovisceral
      avulsions. Contradictory results were found regarding the relation between
      pubovisceral avulsions and urinary symptoms and symptoms of anorectal
      dysfunction. Pubovisceral avulsions, as diagnosed by MR imaging or perineal
      ultrasonography, are associated with higher stages of POP and recurrence of POP
      after surgery.

PMID- 22581244
TI  - Orientobilharzia Dutt & Srivastava, 1955 (Trematoda: Schistosomatidae), a junior
      synonym of Schistosoma Weinland, 1858.
AB  - In the last few decades, phylogenetic studies of the family Schistosomatidae
      based on molecular markers have revealed that members of the genus
      Orientobilharzia Dutt & Srivastava, 1955 belong within Schistosoma Weinland,
      1858. In this study, the original descriptions and redescriptions of
      Orientobilharzia species and related revisions are reviewed, and it is confirmed
      that the morphological characters correspond with the results of the molecular
      studies. The two genera differ only in the number of testes; however, this
      character varies to a large extent within particular genera of the subfamily
      Schistosomatinae and cannot be used to justify the separation of Orientobilharzia
      from Schistosoma. Also, we have verified claims suggesting the synonymy of
      certain species of Orientobilharzia; the four valid species of this genus are
      transferred to Schistosoma and two new synonymies are formally presented. The
      following nomenclatural changes are made: Schistosoma Weinland, 1858 [syn.
      Orientobilharzia Dutt & Srivastava, 1955 (syn. nov.)]; Schistosoma bomfordi
      Montgomery, 1906 (comb. restit.); S. turkestanicum Skrjabin, 1913 (comb. restit.)
      [syns Ori. turkestanica var. tuberculata (Bhalerao, 1932) (syn. nov.) and Ori.
      cheni Hsu & Yang, 1957 (syn. nov.)]; S. dattai (Dutt & Srivastava, 1952) n.
      comb.; and S. harinasutai (Kruatrachue, Bhaibulaya & Harinasuta, 1965) n. comb.
      The generic diagnosis of Schistosoma is amended and a revised key to the
      subfamily Schistosomatinae Stiles & Hassall, 1898 is presented.

PMID- 22581245
TI  - Ultrastructural characteristics of the protonephridial terminal organ and
      associated ducts of adult specimens of the Aspidogastrea, Digenea and Monogenea,
      with comments on the relationships between these groups.
AB  - Transmission electron microscopical observations were made on the protonephridial
      terminal organ and associated ducts of three adult trematodes, the aspidogastrean
      Aspidogaster limacoides Diesing, 1835 and the digeneans Azygia lucii (Muller,
      1776) and Phyllodistomum angulatum Linstow, 1907, and the monogenean
      Ancyrocephalus paradoxus Creplin, 1839. Previously unreported ultrastructural
      details of the terminal organ of adult trematodes include multiple contact sites
      (septate junctions and zonulae adherentes) between the membranes of the terminal
      and adjacent canal cells. Septate junctions traverse the epithelial cytoplasm of
      the canal wall, and the same type of septate junctions are observed within the
      cytoplasmic cord at the level of the tip of the flame tuft in both longitudinal
      and oblique sections of all three trematode species studied. In the
      monopisthocotylean Ancyrocephalus paradoxus, the absence of any junctions in the
      cytoplasmic cord and the presence of septate junction within all of the
      protonephridial ducts are reported. On the basis of the small number of
      monogenean species in which these features have been studied, in relation to the
      size of the group, there seems to be a high diversity in some characters of the
      protonephridial terminal organ. The study confirms that the Aspidogastrea and
      Digenea possess the same morphology of their protonephridial terminal organ and,
      although this differs slightly from that of most members of the Monogenea so far
      studied, it supports previous views on the close relationship of these groups.

PMID- 22581246
TI  - A new acanthocephalan family, the Isthmosacanthidae (Acanthocephala:
      Echinorhynchida), with the description of Isthmosacanthus fitzroyensis n. g., n.
      sp. from threadfin fishes (Polynemidae) of northern Australia.
AB  - Isthmosacanthus fitzroyensis n. g., n. sp. is described from two species of
      protandrous fish, Eleutheronema tetradactylum (Shaw) and Polydactylus macrochir
      (Gunther), from the waters around the coast of northern Australian. The new
      species can be distinguished from all others by the following combination of
      characters: proboscis shape and armature (22 rows of 13-14 hooks), short neck,
      trunk spined anteriorly and having two swellings (one bulbous) with a narrow
      isthmus in between, long tubular lemnisci and six tubular cement glands. Although
      I. fitzroyensis has been confused with a species of Pomphorhynchus Monticelli,
      1905 in the literature, it can be distinguished from all pomphorhynchids,
      including species of Longicollum Yamaguti, 1935 and Pyriproboscis Amin, Abdullah
      & Mhaisen, 2003, by the suite of characters listed above. The placement of the
      species of Pyriproboscis in the Pomphorhynchidae Yamaguti, 1939 is problematical,
      because it has a short neck, two distinct hook types comprising the proboscis
      armature and only two rather than six cement glands. A new family, the
      Isthmosacanthidae n. fam., is erected to contain Isthmosacanthus together with
      Gorgorhynchoides Cable & Linderoth, 1963 and Golvanorhynchus Noronha, Fabio &
      Pinto, 1978, genera having an elongate to clavate proboscis, anterior trunk
      spines, elongate lemnisci, and six tubular cement glands. The validity of this
      determination, based on the importance of cement gland number and phylogenetic
      analysis, is argued.

PMID- 22581247
TI  - A new species of Euryhaliotrematoides Plaisance & Kritsky, 2004 (Monogenea:
      Dactylogyridae) from the gills of the spotted rose snapper Lutjanus guttatus
      (Steindachner) (Perciformes: Lutjanidae).
AB  - Euryhaliotrematoides mehen n. sp. (Monogenea: Dactylogyridae) is described based
      on specimens collected from the gills of the spotted rose snapper Lutjanus
      guttatus (Steindachner) off Mazatlan, Sinaloa, on the northwestern coast of
      Mexico. The synapomorphy of this genus is the presence of a funnel-shaped base of
      the male copulatory organ. This new species differs from all other species of the
      genus by possessing a male copulatory organ with a base with a thickened margin
      and a membranous accessory piece resembling a scarf and covering about 60% of its
      distal region. PCR products of the 28S rRNA (831 bp) and 18S rRNA (662 bp) genes
      were sequenced and submitted to GenBank (accession numbers HQ615997 and JF938069,
      respectively). BLASTn searches revealed no 100% identical hits with the
      previously registered monogenean sequences.

PMID- 22581248
TI  - Description of a new species of Eimeria Schneider, 1875 (Apicomplexa: Eimeriidae)
      from the western Derby eland Taurotragus derbianus derbianus Gray (Artiodactyla:
      Bovidae) in Senegal.
AB  - Examination of faecal samples from semi-captive western Derby elands Taurotragus
      derbianus derbianus Gray, in the Bandia and Fathala Reserves of Senegal, revealed
      the presence of oocysts of the genus Eimeria Schneider, 1875 that we considered
      to represent a new species, Eimeria derbiani n. sp. The new species possesses
      nearly ellipsoidal oocysts (length/width ratio 1.3) with a bi-layered wall and an
      average size of 27.6 * 21.5 MUm. E. derbiani possesses a micropyle covered by a
      micropylar cap and ovoidal, single-layered sporocysts with an average size of
      14.9 * 7.7 MUm, each with a Stieda body. Sporozoites of E. derbiani possess a
      large refractile body and a nucleus. Sporulation lasted for 2 days at 23 degrees
      C. The new species is differentiated from the two species parasitising
      Taurotragus oryx Pallas, E. canna Triffitt, 1924 and E. triffittae Yakimoff,
      1934.

PMID- 22581249
TI  - Sciadicleithrum juruparii n. sp. (Monogenea: Ancyrocephalidae) from the gills of
      Satanoperca jurupari (Heckel) (Osteichthyes: Cichlidae) in the Guama River,
      Amazon Delta, Brazil.
AB  - Sciadicleithrum juruparii n. sp. is described from the gills of the Neotropical
      cichlid fish Satanoperca jurupari (Heckel) caught in the Guama River, in the
      delta of the Amazon River, at Belem, Para State, Brazil. Diagnostic characters of
      the new species are a basally articulated male copulatory organ with clockwise
      coils and an accessory piece; a ventral bar with a median process; similar
      hooklets; vagina in the form of a sclerotised tube; and a sinistral vaginal
      aperture with a sclerotised papilla lying in a small surface depression. It is
      the only species of Sciadicleithrum Kritsky, Thatcher & Boeger, 1989 with a
      medial projection on the ventral bar.

PMID- 22581250
TI  - Rhabdias esculentarum n. sp. (Nematoda: Rhabdiasidae) from green frogs of the
      Rana esculenta species complex in Italy: molecular evidence, morphological
      description and genetic differentiation from its congeners in frogs and toads.
AB  - A new taxon, Rhabdias esculentarum n. sp., is described based on DNA sequence
      analysis at multiple loci (i.e. mtDNA cox-1, 12S rRNA, ITS-1 and partial ITS-2
      regions of the nuclear rDNA) and morphometric analysis carried out on specimens
      collected from the green frogs of the Rana esculenta species complex in Italy
      (i.e. R. lessonae Camerano and R. esculenta Linnaeus, identified genetically by
      diagnostic allozyme loci). Rhabdias esculentarum n. sp. was differentiated
      genetically, at both mitochondrial and nuclear levels, from Rh. bufonis (Schrank,
      1788) (sensu Hartwich, 1972) and Rh. sphaerocephala Goodey, 1924 recovered from
      the toad Bufo bufo Linnaeus collected sympatrically with the specimens of Rana
      lessonae and R. esculenta examined in the present study. Moreover, the new taxon
      proved to be different from the other species of Rhabdias from anurans, which had
      previously been sequenced using the same genes and deposited in GeneBank.
      Phylogenetic analyses (MP and ML) inferred from mitochondrial (mtDNA cox-1 and
      12S ribosomal RNA) and nuclear (ITS-1 and ITS-2 of the rDNA regions) sequences
      datasets were congruent in depicting Rh. esculentarum n. sp. as forming a highly
      supported clade distinct from the sympatric species Rh. bufonis, as well as from
      Rh. sphaerocephala, characterised on the basis of the same loci. Morphometric
      analysis and the differential diagnosis of genetically characterised specimens of
      the new species have revealed differences in several features in comparison with
      the type-species, Rh. bufonis. Material of the latter species included voucher
      specimens from Germany deposited by Hartwich (1972) and other specimens collected
      from B. bufo in Italy. Among the diagnostic characters, the particular cup-shaped
      buccal capsule characterising Rh. esculentarum is clearly different from the tear
      shaped buccal capsule observed in material of R. bufonis obtained from Berlin
      Museum and collected in the same geographical area as the green frogs under
      study. Rh. esculentarum was also found to differ in some measurements and
      allometric characters from Rh. bufonis (sensu Moravec et al., 1997). The data so
      far collected appear to indicate a host-preference of Rh. esculentarum for Rana
      lessonae and R. esculenta, which belong to the R. esculenta hybridogenetic
      species complex in Italy.

PMID- 22581251
TI  - Cavearhynchus, a new genus of tapeworm (Cestoda: Trypanorhyncha: Pterobothriidae)
      from Himantura lobistoma Manjaji-Matsumoto & Last, 2006 (Rajiformes) off Borneo,
      including redescriptions and new records of species of Pterobothrium Diesing,
      1850.
AB  - A new genus of trypanorhynch cestode is described from the tubemouth whipray
      Himantura lobistoma Manjaji-Matsumoto & Last, 2006 in the South China Sea off
      Malaysian Borneo. Cavearhynchus foveatus n. g., n. sp. possesses four pedicellate
      bothria in a cruciform arrangement, a heteroacanthous, heteromorphous metabasal
      tentacular armature with five hooks per principle row and an alternating
      longitudinal file of intercalary hooks on the bothrial surface of each tentacle,
      but lacks prebulbar organs and gland-cells within the bulbs. It, thus, closely
      resembles taxa belonging to the lacistorhynchoid family Pterobothriidae Pintner,
      1931. However, the new genus differs from other genera within this family in the
      possession of bothrial pits. Although a distinguishing characteristic of the
      superfamily Otobothrioidea Dollfus, 1942, representatives of this group exhibit
      two bothria and the bothrial pits are lined with spiniform microtriches, whereas
      the pit-like structures.of C. foveatus n. g., n. sp. entirely lack microtriches.
      Redescriptions of two species of Pterobothrium, namely P. lesteri Campbell &
      Beveridge, 1996 and P. platycephalum (Shipley & Hornell, 1906) Dollfus, 1930 are
      provided from material collected off Borneo and several localities off Australia.
      Moreover, new host and locality records are added for P. australiense Campbell &
      Beveridge, 1996 and P. pearsoni (Southwell, 1929) Beveridge & Campbell, 1989.

PMID- 22581252
TI  - Three new species of Merizocotyle Cerfontaine, 1894 (Monogenea: Monocotylidae)
      from the nasal tissues of dasyatid rays collected off Malaysian and Indonesian
      Borneo.
AB  - Three new species of Merizocotyle Cerfontaine, 1894 (Monogenea: Monocotylidae)
      are described from the nasal tissues of stingrays collected off Borneo.
      Merizocotyle macrostrobus n. sp. is described from the dwarf whipray Himantura
      walga (Muller & Henle) collected in shallow waters off Sematan, Sarawak,
      Malaysia. This species can be distinguished from the other members of the genus
      by the morphology of the sclerotised male copulatory organ, which is long with
      many twists and loops. The vaginae of this species are also long and looped.
      Merizocotyle papillae n. sp. is described from the roughnose stingray Pastinachus
      solocirostris Last, Manjaji & Yearsley collected off Sematan and Mukah, Sarawak,
      Malaysia. It is distinguished from the other species of Merizocotyle by the
      morphology of the male copulatory organ, which is a sclerotised tube that expands
      slightly and then tapers at the distal end, and by the presence of papillae on
      the dorsal edge of the haptor. Merizocotyle rhadinopeos n. sp. is described from
      the whitenose whip ray Himantura uarnacoides (Bleeker) collected off Manggar,
      East Kalimantan, Indonesia. It can be differentiated by the male copulatory
      organ, which is a short, narrow, curved, sclerotised tube tapering distally, and
      the path of the ovary, which runs anteriorly to the base of the ootype. We also
      provide details of new host and/or locality records for M. australensis (Beverley
      Burton & Williams, 1989) Chisholm, Wheeler & Beverley-Burton, 1995, M. icopae
      Beverley-Burton & Williams, 1989 and M. pseudodasybatis (Hargis, 1955) Chisholm,
      Wheeler & Beverley-Burton, 1995.

PMID- 22581253
TI  - Dissecting the clinical phenotype associated with mosaic type-2 NF1
      microdeletions.
AB  - Patients with large deletions of the NF1 gene and its flanking regions (termed
      NF1 microdeletions) generally exhibit more severe clinical manifestations of
      neurofibromatosis type-1 (NF1). Here, we have investigated the clinical phenotype
      displayed by eight patients harbouring mosaic type-2 NF1 microdeletions. These
      patients did not exhibit facial dysmorphism, attention deficit hyperactivity
      disorder, delayed cognitive development and/or learning disabilities, cognitive
      impairment, congenital heart disease, hyperflexibility of joints, large hands and
      feet, muscular hypotonia or bone cysts. All these features have previously been
      reported to be disproportionately associated with germline (i.e. non-mosaic) type
      1 NF1 microdeletions as compared with the general NF1 population. Plexiform
      neurofibromas were also less prevalent in patients with mosaic type-2 NF1
      microdeletions as compared with patients carrying constitutional (germline) type
      1 NF1 microdeletions. Five of the eight patients with mosaic type-2 deletions
      investigated here had 20-250 cutaneous neurofibromas, but only one of them
      exhibited a high load of cutaneous neurofibromas (N > 1,000). By contrast, a
      previous study indicated a high burden of cutaneous neurofibromas (N > 1,000) in
      50% of adult patients with germline type-1 NF1 deletions. Patients with germline
      type-1 NF1 microdeletions have been reported to have an increased lifetime risk
      of 16-26% for a malignant peripheral nerve sheath tumour (MPNST). In this study,
      one of the eight investigated mosaic type-2 microdeletion patients developed an
      MPNST. We conclude that patients with mosaic type-2 NF1 microdeletions may also
      be at an increased risk of MPNSTs despite their generally milder disease
      manifestations as compared with germline type-1 NF1 microdeletions.

PMID- 22581254
TI  - Association between chronic hepatitis C virus infection and high levels of
      circulating N-terminal pro-brain natriuretic peptide.
AB  - The association between HCV infection and myocardial disorders remains unclear.
      This study aimed to assess whether or not HCV infection influences myocardial
      dysfunction by the use of NT-proBNP, a sensitive marker of myocardial
      dysfunction. A total of 198 participants [99 patients with chronic HCV infection
      (aged 46-68 years) and 99 anti-HCV-negative sex and age matched controls] were
      examined. Serum HCV-RNA level and HCV genotype were tested and liver biopsy was
      done only for the patient group. The NT-proBNP concentration of the HCV patients
      (mean 71.6 +/- 79.1 pg/ml; median 46.0 pg/ml, range 5.0-400.0) was significantly
      higher than that of the controls (mean 39.8 +/- 24.4 pg/ml; median 35.8 pg/ml,
      range 7.0-108.0) (P < 0.05). 20.0 % of the HCV patients and 0.6 % of the controls
      had high NT-proBNP (higher than 125 pg/ml; the single cut off point for patients
      under 75 years of age) (P < 0.05). Stepwise multiple regression analysis revealed
      that chronic HCV infection was independently correlated with NT-proBNP level
      after adjustment for parameters that might influence NT-proBNP (P = 0.005). Our
      data suggest that chronic HCV infection is associated with increased NT-proBNP,
      indicating that chronic HCV infection might induce myocardial dysfunction.

PMID- 22581255
TI  - Skeletal and extraskeletal actions of denosumab.
AB  - Osteoclasts and osteoblasts define skeletal mass, structure and strength through
      their respective actions in resorbing and forming bone. This remodeling process
      is orchestrated by the actions of hormones and growth factors, which regulate a
      cytokine system comprising the receptor activator of nuclear factor kappaB ligand
      (RANKL), its receptor RANK and the soluble decoy receptor osteoprotegerin (OPG).
      Bone resorption depends on RANKL, which determines osteoclast formation, activity
      and survival. Importantly, cells of the osteoblastic lineage mainly provide RANKL
      and therefore, are central in the regulation of osteoclast functions. Catabolic
      effects of RANKL are inhibited by OPG, a TNF receptor family member that binds
      RANKL, thereby preventing the activation of its receptor RANK, which is expressed
      by osteoclast precursors. Because this cytokine network is pivotal for the
      regulation of bone mass in health and diseases, including osteoporosis,
      rheumatoid arthritis and malignant bone conditions, it has been successfully used
      for the generation of a targeted therapy to block osteoclast actions. The
      clinical approval of denosumab, a fully monoclonal antibody against RANKL,
      provides a novel option to treat bone diseases with a potent, targeted and
      reversible inhibitor of bone resorption. Although RANKL is also expressed by
      endothelial cells, T lymphocytes, synovial fibroblasts and various tumor cells,
      no meaningful clinical extraskeletal effects have been reported after
      administration of denosumab. This article summarizes the molecular and cellular
      basis of the RANKL/RANK/OPG system and presents preclinical and clinical studies
      on the skeletal actions of denosumab.

PMID- 22581256
TI  - Fish oil positively regulates anabolic signalling alongside an increase in whole
      body gluconeogenesis in ageing skeletal muscle.
AB  - PURPOSE: Fish oil, containing mainly long-chain n-3 polyunsaturated fatty acids
      (LCn-3PUFA), has been found to acutely stimulate protein synthesis and insulin
      mediated glucose metabolism. However, the underlying mechanism and more prolonged
      effect of fish oil during ageing remain to be determined. METHODS: Fish oil
      (EPAX6000; 49.6 % eicosapentaenoic acid, 50.4 % docosahexaenoic acid) or control
      oil (60 % olive, 40 % soy) supplementation was delivered, via chocolate-derived
      sweets, to rats for 8 weeks. Throughout the study, food intake and body weight
      were recorded and body composition was investigated using EchoMRI. During the
      last 40 min of a 6 h infusion, with labelled dextrose ([U-(13)C]glucose) and
      amino acids ([1-(13)C]phenylalanine), blood samples were collected to assess
      glucose and phenylalanine kinetics. Soleus and longissimus dorsi muscles were
      extracted for protein and mRNA analyses. RESULTS: Fish oil had no effect on food
      intake or body composition. An increased whole-body glucose turnover, mainly
      accounted for via an increase in endogenous glucose production, was observed with
      fish oil feeding. No effects on whole-body phenylalanine turnover were observed.
      In longissimus dorsi, fish oil augmented the phosphorylation of phosphoinositide
      3-kinase (PI3K)([Tyr458]) (P = 0.04) and 70 kDa ribosomal protein S6 kinase
      (p70s6k)([Thr389]) (P = 0.04). There were no differences in protein kinase B
      (Akt)([Ser473]), mammalian target of rapamycin (mTOR)([Ser2448]), protein
      phosphatase 2A (PP2A) 56 kDa regulatory B subunit gamma (PP2A-B56-gamma),
      forkhead box containing proteins O-subclass 3a (FOX03a)([Ser253]) or inflammatory
      markers (Interleukin-6, Interleukin-1 beta, tumour necrosis factor-alpha, and
      cyclooxygenase-2). CONCLUSIONS: Our data suggest that the fish oil may stimulate
      endogenous glucose production and increase anabolic signalling in ageing rats.

PMID- 22581257
TI  - Sacroiliac joint pain after lumbar/lumbosacral fusion: current knowledge.
AB  - Recently, the sacroiliac joint (SIJ) has gained increased attention as a source
      of persistent or new pain after lumbar/lumbosacral fusion. The underlying
      pathophysiology of SIJ pain may be increased mechanical load, iliac crest bone
      grafting, or a misdiagnosis of SIJ syndrome. Imaging studies show more frequent
      degeneration of the SIJ in patients with lumbar/lumbosacral fusion than in
      patients without such fusion. Using injection tests, it has been shown that SIJ
      pain is the cause of persistent symptoms in a considerable number of patients
      after fusion surgery. Recent articles reporting on surgical outcomes of SIJ
      fusion include a high percentage of patients who had lumbar/lumbosacral fusion or
      surgery before, although well-controlled clinical studies are necessary to assess
      the efficacy of surgical treatment. Taking these findings into consideration, the
      possibility that the SIJ is the source of pain should be considered in patients
      with failed back surgery syndrome after lumbar/lumbosacral fusion.

PMID- 22581258
TI  - The effect of omega-3 fatty-acid supplements on perioperative bleeding following
      posterior spinal arthrodesis.
AB  - PURPOSE: To investigate the effect of omega-3 fatty-acid supplements (n-3FA) on
      bleeding during posterior spinal arthrodesis. METHODS: We reviewed all one- or
      two-level posterolateral lumbar decompression/fusions with or without interbody
      fusion by five surgeons within 3 years. Patients taking n-3FA preoperatively were
      matched 1:2 with controls based on procedure, surgeon and operative time.
      Patients with abnormal coagulation parameters, known bleeding disorders or other
      medications that could affect surgical blood loss were excluded. RESULTS: Twenty
      eight patients met inclusion criteria. The n-3FA and control groups were similar
      with respect to gender, age, body mass index, operative time, and preoperative
      use of non-steroidal anti-inflammatory drugs. The n-3FAs were stopped an average
      of 5.2 days before surgery (range 1-10). Mean estimated blood loss (EBL) was 697
      ml in the n-3FA group and 771 ml in the control group (p = 0.36). Mean transfused
      volume of Cell Saver (CS) was 282 ml in the n-3FA group and 321 ml in the control
      group (p = 0.30). A post hoc power analysis showed that the study was powered to
      detect a minimum difference of 105 ml for EBL and 50 ml for CS. The multivariate
      generalized estimating equation did not show a significant difference between
      groups for EBL or CS (p = 0.35 and p = 0.29, respectively). Secondary outcomes
      including drop in postoperative hemoglobin, transfusion requirement,
      complications and surgical drain output were similar between the two groups.
      CONCLUSIONS: The n-3FA use did not contribute to higher perioperative blood loss
      during spinal arthrodesis.

PMID- 22581260
TI  - Porphyrin dyads linked by a rotatable 3,3'-biphenyl scaffold: a new binding motif
      for small ditopic molecules.
AB  - Synthetic access to a set of metallo- and free base bis-porphyrins has been
      provided by a stepwise approach involving sequential peptide and Suzuki
      couplings. Linking these porphyrins through a 3,3'-biphenyl bridge enables
      cooperative binding to ditopic ligands such as the bipyridyls. Association
      constants and binding stoichiometry has been determined by
      spectroscopic/spectrophotometric means and the differences in the binding
      affinities of a small series of diaza ligands is discussed in the context of
      structural fit and microscopic association constants.

PMID- 22581259
TI  - Neuroprotection in diabetic retinopathy.
AB  - Diabetic retinopathy (DR) has been considered to be a microcirculatory disease of
      the retina. However, there is emerging evidence to suggest that retinal
      neurodegeneration is an early event in the pathogenesis of DR, which may
      antedate, and also participates in, the microcirculatory abnormalities that occur
      in DR. Therefore, the study of the underlying mechanisms that lead to
      neurodegeneration will be essential for identifying new therapeutic targets in
      the early stages of DR. Elevated levels of glutamate, oxidative stress, the
      overexpression of the renin-angiotensin system and the upregulation of RAGE play
      an essential role in the retinal neurodegeneration induced by diabetes. Finally,
      the balance between the neurotoxic and neuroprotective factors is crucial in
      determining the survival of retinal neurons. In this review we will focus on
      neurotrophic factors already synthesized by the retina in physiological
      conditions as a new therapy strategy for neuroprotection.

PMID- 22581262
TI  - Triptolide triggers the apoptosis of pancreatic cancer cells via the
      downregulation of Decoy receptor 3 expression.
AB  - PURPOSE: Triptolide (TPL) is a diterpenoid triepoxide that effectively induces
      apoptosis in a wide variety of cancer cells. However, the detailed mechanism by
      which TPL activates caspase cascade remains elusive. This study aimed to examine
      the antitumor effects of TPL against pancreatic cancer and investigate the
      underlying mechanism. METHODS: Cell proliferation was evaluated by sulforhodamine
      B assay. The apoptosis was evaluated by caspase activity assay, Western blot and
      flow cytometry. DcR3 level was measured by ELISA. AsPC-1 xenografts were
      established to compare the in vivo antitumor effects of TPL and Gemcitabine.
      RESULTS: TPL inhibited the proliferation and induced the apoptosis of pancreatic
      cancer cells in a dose- and time-dependent manner. TPL also inhibited DcR3
      expression in a dose- and time-dependent manner. siRNA-mediated DcR3 knockdown
      sensitized pancreatic cancer cells to TPL-induced apoptosis. In vivo, DcR3 siRNA
      significantly enhanced TPL-induced apoptosis and tumor growth inhibition.
      Moreover, TPL showed less toxicity compared to Gemcitabine in mice model.
      CONCLUSIONS: TPL induces the apoptosis of pancreatic cancer cells via the
      downregulation of DcR3 expression and has the potential as an effective agent
      against pancreatic cancer.

PMID- 22581263
TI  - Cutaneous metastasis as a initial presentation in advanced non-small cell lung
      cancer and its poor survival prognosis.
AB  - AIM: Cutaneous metastases in primary advanced non-small cell lung cancer (NSCLC)
      rarely occur in comparison with other site involvement. The incidence of
      cutaneous metastases and its prognosis is not well known. Data from a 2,130
      patients with advanced NSCLC were analyzed, in order to assess the incidence and
      survival prognosis of cutaneous metastases in primary advanced NSCLC. METHODS:
      The clinical data of 2,130 patients with advanced NSCLC who were admitted to
      Zhejiang cancer Hospital from January 1998 to December 2007 were retrospectively
      analyzed. Data pertaining to their presentation, diagnosis treatment, pathology,
      follow-up, and clinical course were documented. Clinical characteristics were
      investigated based on the clinical and pathologic records. All of the cutaneous
      metastases were confirmed by cytology or biopsy. Survival analysis was made by
      Kaplan-Meier method. The Cox regression model was performed to analyze the
      relationship between the influential factors and the overall survival. RESULTS:
      Among the 2,130 advanced NSCLC patients as initial diagnosis, 60 (2.8 %)
      demonstrated abnormally cutaneous metastases. Fifteen patients with only
      cutaneous metastases, forty-five subjects combined with other site metastasis.
      There were 56 patients who received chemotherapy, and the first-line disease
      control rate was 33.9 %, the median free progression survival time was 1.9
      months. There were significant differences in overall survival between cutaneous
      metastases and non-cutaneous metastases arms (3.9 vs. 10.0 months, P < 0.001).
      Multivariate analyses revealed that performance status and chemotherapy efficacy
      statistically associated with overall survival. CONCLUSIONS: This retrospective
      study indicated that 2.8 % of advanced NSCLC patients showed cutaneous metastases
      as an initial presentation. Cutaneous metastases of lung cancer are of poor
      prognosis.

PMID- 22581261
TI  - DOCK8 functions as an adaptor that links TLR-MyD88 signaling to B cell
      activation.
AB  - The adaptors DOCK8 and MyD88 have been linked to serological memory. Here we
      report that DOCK8-deficient patients had impaired antibody responses and
      considerably fewer CD27(+) memory B cells. B cell proliferation and
      immunoglobulin production driven by Toll-like receptor 9 (TLR9) were considerably
      lower in DOCK8-deficient B cells, but those driven by the costimulatory molecule
      CD40 were not. In contrast, TLR9-driven expression of AICDA (which encodes the
      cytidine deaminase AID), the immunoglobulin receptor CD23 and the costimulatory
      molecule CD86 and activation of the transcription factor NF-kappaB, the kinase
      p38 and the GTPase Rac1 were intact. DOCK8 associated constitutively with MyD88
      and the tyrosine kinase Pyk2 in normal B cells. After ligation of TLR9, DOCK8
      became tyrosine-phosphorylated by Pyk2, bound the Src-family kinase Lyn and
      linked TLR9 to a Src-kinase Syk-transcription factor STAT3 cascade essential for
      TLR9-driven B cell proliferation and differentiation. Thus, DOCK8 functions as an
      adaptor in a TLR9-MyD88 signaling pathway in B cells.

PMID- 22581264
TI  - Proteomics and systems biology for understanding diabetic nephropathy.
AB  - Like many diseases, diabetic nephropathy is defined in a histopathological
      context and studied using reductionist approaches that attempt to ameliorate
      structural changes. Novel technologies in mass spectrometry-based proteomics have
      the ability to provide a deeper understanding of the disease beyond classical
      histopathology, redefine the characteristics of the disease state, and identify
      novel approaches to reduce renal failure. The goal is to translate these new
      definitions into improved patient outcomes through diagnostic, prognostic, and
      therapeutic tools. Here, we review progress made in studying the proteomics of
      diabetic nephropathy and provide an introduction to the informatics tools used in
      the analysis of systems biology data, while pointing out statistical issues for
      consideration. Novel bioinformatics methods may increase biomarker
      identification, and other tools, including selective reaction monitoring, may
      hasten clinical validation.

PMID- 22581265
TI  - Differential response to EGFR- and VEGF-targeted therapies in patient-derived
      tumor tissue xenograft models of colon carcinoma and related metastases.
AB  - Heterogeneity in primary tumors and related metastases may result in failure of
      antitumor therapies, particularly in targeted therapies for the treatment of
      cancer. In this study, patient-derived tumor tissue (PDTT) xenograft models of
      colon carcinoma with lymphatic and hepatic metastases were used to evaluate the
      response to EGFR- and VEGF-targeted therapies. Our results showed that primary
      colon carcinoma and its corresponding lymphatic and hepatic metastases have a
      different response rate to anti-EGFR (cetuximab) and anti-VEGF (bevacizumab)
      therapies. However, the underlying mechanism of these types of phenomenon is
      still unclear. To investigate whether such phenomena may result from the
      heterogeneity in primary colon carcinoma and related metastases, we compared the
      expression levels of cell signaling pathway proteins using immunohistochemical
      staining and western blotting, and the gene status of KRAS using pyrosequencing
      in the same primary colon carcinoma and its corresponding lymphatic and hepatic
      metastatic tissues which were used for establishing the PDTT xenograft models.
      Our results showed that the expression levels of EGFR, VEGF, Akt/pAkt, ERK/pERK,
      MAPK/pMAPK, and mTOR/pmTOR were different in primary colon carcinoma and matched
      lymphatic and hepatic metastases although the KRAS gene status in all cases was
      wild-type. Our results indicate that the heterogeneity in primary colon carcinoma
      and its corresponding lymphatic and hepatic metastases may result in differences
      in the response to dual-inhibition of EGFR and VEGF.

PMID- 22581266
TI  - Toll-like receptor-induced inflammatory cytokines are suppressed by gain of
      function or overexpression of Galpha(i2) protein.
AB  - Previous studies have implicated a role of Galpha(i) proteins as co-regulators of
      Toll-like receptor (TLR) activation. These studies largely derived from examining
      the effect of Galpha(i) protein inhibitors or genetic deletion of Galpha(i)
      proteins. However, the effect of increased Galpha(i) protein function or
      Galpha(i) protein expression on TLR activation has not been investigated. We
      hypothesized that gain of function or increased expression of Galpha(i) proteins
      suppresses TLR2- and TLR4-induced inflammatory cytokines. Novel transgenic mice
      with genomic "knock-in" of a regulator of G protein signaling (RGS)-insensitive
      Gnai2 allele (Galpha(i2)(G184S/G184S) ; GS/GS) were employed. These mice express
      essentially normal levels of Galpha(i2) protein; however, the Galpha(i2) is
      insensitive to its negative regulator RGS thus rendering more sustained
      Galpha(i2) protein activation following ligand/receptor binding. In subsequent
      studies, we generated Raw 264.7 cells that stably overexpress Galpha(i2) protein
      (Raw Galpha(i2)). Peritoneal macrophages, splenocytes, and mouse embryonic
      fibroblasts (MEF) were isolated from WT and GS/GS mice and were stimulated with
      LPS, Pam3CSK4, or Poly (I:C). We also subjected WT and GS/GS mice to endotoxic
      shock (LPS, 25 mg/kg i.p.) and plasma tumor necrosis factor alpha (TNF-alpha) and
      interleukin (IL)-6 production were determined. We found that in vitro LPS and
      Pam3CSK4-induced TNF-alpha, and IL-6 production are decreased in macrophages from
      GS/GS mice compared with WT mice (p < 0.05). In vitro, LPS and Pam3CSK4 induced
      IL-6 production in splenocytes, and in vivo, LPS-induced IL-6 were suppressed in
      GS/GS mice. Poly (I:C)-induced TNF-alpha, and IL-6 in vitro demonstrated no
      difference between GS/GS mice and WT mice. LPS-induced IL-6 production was
      inhibited in MEFs from GS/GS mice similarly to macrophage and splenocytes. In
      parallel studies, Raw Galpha(i2) cells also exhibit decreased TNF-alpha and IL-6
      production in response to LPS and Pam3CSK4. These studies support our hypothesis
      that Galpha(i2) proteins are novel negative regulators of TLR activation.

PMID- 22581267
TI  - Systems GMM estimates of the health care spending and GDP relationship: a note.
AB  - This paper utilizes the systems generalized method of moments (GMM) [Arellano and
      Bover (1995) J Econometrics 68:29-51; Blundell and Bond (1998) J Econometrics
      87:115-143], and panel Granger causality [Hurlin and Venet (2001) Granger
      Causality tests in panel data models with fixed coefficients. Mime'o, University
      Paris IX], to investigate the health care spending and gross domestic product
      (GDP) relationship for organisation for economic co-operation and development
      countries over the period 1960-2007. The system GMM estimates confirm that the
      contribution of real GDP to health spending is significant and positive. The
      panel Granger causality tests imply that a bi-directional causality exists
      between health spending and GDP. To this end, policies aimed at raising health
      spending will eventually improve the well-being of the population in the long
      run.

PMID- 22581268
TI  - Early identification of leptospirosis as an ignored cause of multiple organ
      dysfunction syndrome.
AB  - Leptospirosis is the most common zoonosis in the world but remains underreported,
      owing to protean manifestations and ignorance about the disease among health care
      providers in Taiwan. From September 2000 to March 2006, surveillance of 455
      patients with multiple organ dysfunction syndrome with unclear cause or clinical
      suspicion of leptospirosis was performed. Diagnosis was further confirmed by
      microscopic agglutination test or isolation of Leptospira. Cases were classified
      as excluded based on confirmed etiology other than leptospirosis or negative
      paired serologic test. Forty-two patients were confirmed as having leptospirosis,
      which accounted for 9.2% of total patients with multiple organ dysfunction
      syndrome. Forty-nine excluded cases were identified for a case-control analysis
      for clinical distinction. The most common presentations of leptospirosis were
      fever (97.6%), acute kidney injury (85.7%), and jaundice (61.9%). The
      leptospirosis group showed lower urine specific gravity (cutoff value, 1.0145)
      and enlarged kidney size (cutoff value, 11.05 cm) as compared with the excluded
      cases by multivariate logistics regression. Delayed antibiotic administration
      prolongs the duration of hospitalization (R2 = 0.486, P < 0.01). No mortality has
      been found in the leptospirosis group after initiation in 2003 of rapid
      immunoglobulin M serology assay that showed considerably high sensitivity and
      specificity. Leptospirosis accounts for a salient cause of multiple organ
      dysfunctions in Taiwan. Early awareness of leptospirosis by distinct
      presentations, followed by prompt antibiotics therapy, can dramatically save the
      patients. The easily performed rapid immunoglobulin M serology assay is suitable
      as a rapid screening test for the diagnosis of leptospirosis.

PMID- 22581269
TI  - A finite element method to correct deformable image registration errors in low
      contrast regions.
AB  - Image-guided adaptive radiotherapy requires deformable image registration to map
      radiation dose back and forth between images. The purpose of this study is to
      develop a novel method to improve the accuracy of an intensity-based image
      registration algorithm in low-contrast regions. A computational framework has
      been developed in this study to improve the quality of the 'demons' registration.
      For each voxel in the registration's target image, the standard deviation of
      image intensity in a neighborhood of this voxel was calculated. A mask for high
      contrast regions was generated based on their standard deviations. In the masked
      regions, a tetrahedral mesh was refined recursively so that a sufficient number
      of tetrahedral nodes in these regions can be selected as driving nodes. An
      elastic system driven by the displacements of the selected nodes was formulated
      using a finite element method (FEM) and implemented on the refined mesh. The
      displacements of these driving nodes were generated with the 'demons' algorithm.
      The solution of the system was derived using a conjugated gradient method, and
      interpolated to generate a displacement vector field for the registered images.
      The FEM correction method was compared with the 'demons' algorithm on the
      computed tomography (CT) images of lung and prostate patients. The performance of
      the FEM correction relating to the 'demons' registration was analyzed based on
      the physical property of their deformation maps, and quantitatively evaluated
      through a benchmark model developed specifically for this study. Compared to the
      benchmark model, the 'demons' registration has the maximum error of 1.2 cm, which
      can be corrected by the FEM to 0.4 cm, and the average error of the 'demons'
      registration is reduced from 0.17 to 0.11 cm. For the CT images of lung and
      prostate patients, the deformation maps generated by the 'demons' algorithm were
      found unrealistic at several places. In these places, the displacement
      differences between the 'demons' registrations and their FEM corrections were
      found in the range of 0.4 and 1.1 cm. The mesh refinement and FEM simulation were
      implemented in a single thread application which requires about 45 min of
      computation time on a 2.6 GHz computer. This study has demonstrated that the FEM
      can be integrated with intensity-based image registration algorithms to improve
      their registration accuracy, especially in low-contrast regions.

PMID- 22581271
TI  - Beyond renal cell carcinoma: rare and unusual renal masses.
AB  - The vast majority of primary renal masses represent clear cell or papillary renal
      cell carcinomas, angiomyolipomas, or transitional cell carcinomas. However, a
      number of more rare masses can also be encountered, many of which can be very
      difficult to differentiate from these more common entities based on their imaging
      features. These uncommon entities include metanephric adenoma, epithelioid
      angiomyolipoma, medullary renal cell carcinomas, multilocular cystic nephroma,
      hemangiopericytoma, hemangioma, leiomyoma, leiomyosarcoma, solitary fibrous
      tumor, renal plasmacytomas, and mixed epithelial and stromal tumors. In some
      cases, certain clinical and imaging features can allow one of these unusual
      entities to be placed in the differential diagnosis, including patient age,
      degree of tumor enhancement, presence of underlying sickle cell trait or sickle
      cell disease, the presence of a cystic component to the tumor, and tumor
      morphology. Even if a radiologist is unable to make a specific diagnosis,
      knowledge of these entities is important, as it allows radiologists to guide post
      surgical follow-up, as well to understand the most common sites of metastatic
      disease.

PMID- 22581270
TI  - Social functioning in youth with anxiety disorders: association with anxiety
      severity and outcomes from cognitive-behavioral therapy.
AB  - Social functioning was assessed using the Child Behavior Checklist and Teacher
      Report Form for children with anxiety disorders who participated in a randomized
      clinical trial (N = 161, aged 7-14). Significant relationships were found between
      severity of children's principal anxiety disorder and most measures of social
      functioning, such that poorer social functioning was associated with more severe
      anxiety. Among youth who received cognitive-behavioral therapy (n = 111),
      significant associations were found between parent-reported social competence and
      both absence of principal anxiety disorder and lower anxiety severity at
      posttreatment and 1-year follow-up, controlling for the severity of the child's
      principal anxiety disorder at pretreatment. Findings support a relationship
      between anxiety severity and social difficulties, and suggest the importance of
      social competence for a favorable treatment response.

PMID- 22581272
TI  - Synchronous small bowel and atypical primary leiomyosarcoma of inferior vena cava
      in a patient with RB1 mutation.
AB  - A 72-year-old Caucasian man presenting with non-specific upper abdominal pain had
      asymmetric soft tissue thickening of the small bowel wall on computed tomography
      (CT), which was pathologically proven to be leiomyosarcoma (LMS). At the same
      time point patient had incidentally but retrospectively detected lesion in IVC on
      CT scan which was subsequently imaged with PET/CT and MRI and was histologically
      proven to be also LMS. We present clinical and imaging features along with
      pedigree of this unique case of synchronous primary LMS involving the small bowel
      and inferior vena cava in a patient with RB1 gene mutation and a significant
      family history of multiple malignancies. To our knowledge, the synchronous
      primary LMS at two different sites has not been described. Clinicians and
      radiologists should keep in mind the possibility of a synchronous primary LMS in
      patients with genetic predisposition before making the diagnosis of a metastatic
      lesion or other malignancy as localized primary tumors remain potentially
      curable, whereas metastatic sarcoma is most often incurable. 

PMID- 22581273
TI  - If you don't look, you won't see: intravital multiphoton imaging of primary and
      metastatic breast cancer.
AB  - A fundamental hallmark of cancer is progression to metastasis and the growth of
      breast cancer metastases in lung, bone, liver and/or brain causes fatal
      complications. Unfortunately, the cellular and biochemical mechanisms of the
      metastatic process remain ill-defined. Recent application of intravital
      multiphoton microscopy (MP-IVM) to image fluorescently labeled cells in mouse
      models of cancer has allowed dynamic observation of this multi-step process at
      the cellular and subcellular levels. In this article, we discuss the use of MP
      IVM in studies of breast cancer metastasis, as well as surgical techniques for
      exposing tumors prior to imaging. We also describe a versatile multiphoton
      microscope for imaging tumor-stroma interactions.

PMID- 22581274
TI  - Risk adjustment in health insurance exchanges for individuals with mental
      illness.
AB  - OBJECTIVE: In 2014, an estimated 15 million individuals who currently do not have
      health insurance, including many with chronic mental illness, are expected to
      obtain coverage through state insurance exchanges. The authors examined how two
      mechanisms in the Affordable Care Act (ACA), namely, risk adjustment and
      reinsurance, might perform to ensure the financial solvency of health plans that
      have a disproportionate share of enrollees with mental health conditions. Risk
      adjustment is an ACA provision requiring that a federal or state exchange move
      funds from insurance plans with healthier enrollees to plans with sicker
      enrollees. Reinsurance is a provision in which all plans in the state contribute
      to an overall pool of money that is used to reimburse costs to individual market
      plans for expenditures of any individual enrollee that exceed a high
      predetermined level. METHOD: Using 2006--2007 claims data from a sample of
      private and public health plans, the authors compared expected health plan
      compensation under diagnosis-based risk adjustment with actual health care
      expenditures, under different assumptions for chronic mental health and medical
      conditions. Analyses were conducted with and without the addition of $100,000
      reinsurance. RESULTS: Risk adjustment performed well for most plans. For some
      plans with a high share of enrollees with mental health conditions, underpayment
      was substantial enough to raise concern. Reinsurance appeared to be helpful in
      addressing the most serious underpayment problems remaining after risk
      adjustment. Risk adjustment performed similarly for health plan cohorts that had
      a disproportionate share of enrollees with chronic mental health and medical
      conditions. CONCLUSIONS: Cost models indicate that the regulatory provisions in
      the ACA requiring risk adjustment and reinsurance can help protect health plans
      covering treatment for mentally ill individuals against risk selection. This
      model analysis may be useful for advocates for individuals with mental illness in
      considering their own state's insurance exchange.

PMID- 22581275
TI  - Long-term treatment with methanandamide attenuates LPS-induced periodontitis in
      rats.
AB  - OBJECTIVE: Evidence exists of the anti-inflammatory and immunological properties
      of endocannabinoids in various tissues; the aim of the present study was
      therefore to assess the effect of long-term treatment with the synthetic
      cannabinoid methanandamide (Meth-AEA) on the progression of periodontitis in
      rats. MATERIALS AND METHODS: Periodontitis was induced by injecting LPS (1 mg/ml)
      into the gingiva around the neck of the first upper and lower molars, and into
      the inter-dental space between the first and second molars. This protocol was
      repeated for 6 weeks on days 1, 3, and 5 of each week. RESULTS: Long-term
      treatment with topical Meth-AEA (500 ng/ml), applied daily to gingival tissue of
      rats induced with periodontitis, significantly diminished the alveolar bone loss,
      measured as the distance between the cemento-enamel junction and the alveolar
      crest, in both maxillary and mandibular first molars, compared to rats without
      treatment (P < 0.05). The treatment also reduced the production of some
      biological mediators of periodontal disease augmented by LPS, such as tumor
      necrosis factor alpha (from 119.4 +/- 9.9 pg/mg protein to 75.1 +/- 10.8, P <
      0.05) and nitric oxide produced by inducible nitric oxide synthase (from 507.7 +/
      107.1 pmol/min/mg protein to 163.1 +/- 53.9, P < 0.01). CONCLUSION: These
      results demonstrate the beneficial effects of treatment with Meth-AEA on gingival
      tissue of rats with periodontitis.

PMID- 22581276
TI  - Probiotics for the treatment of inflammatory bowel disease.
AB  - Probiotics are organisms which provide a desired and beneficial effect on human
      health. With recent evidence implicating a disruption in the balance of the
      gastrointestinal microbiome and intestinal immunity as a potential trigger for
      inflammatory bowel disease (IBD), there has been growing interest in using
      probiotics as an adjunct to standard anti-inflammatory and immune suppressing
      therapy. Animal models describe potential and plausible mechanisms of action for
      probiotics to counter inflammation of colonic mucosa. Although there are
      insufficient data to recommend probiotics in ulcerative colitis or Crohn's
      disease, good evidence supports the use of specific probiotics for maintenance of
      remission in pouchitis. Although there are limited regulatory standards for the
      agents, probiotics are relatively safe with minimal reported side effects or
      contraindications. More rigorous studies need to be published supporting efficacy
      and safety of these agents before they become a mainstay of IBD medical
      treatment.

PMID- 22581277
TI  - Association between metabolic syndrome, BMI, and serum vitamin D concentrations
      in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is the most common autoimmune arthritis. The impact of
      chronic inflammation on atherosclerosis and insulin resistance has been observed
      in several autoimmune diseases. On the other hand, metabolic syndrome (MetS); a
      cluster of traditional risk factors for atherosclerosis and diabetes seems to be
      prevalent in RA patients. It is reasonable to think that protective factors
      against inflammation can protect patients against atherosclerosis and diabetes,
      too. Vitamin D (Vit D), a novel immunomodulator, is recently considered to play a
      protective role against cardiovascular diseases, insulin resistance, and obesity.
      This cross-sectional study was designed to evaluate the impact of serum Vit D on
      MetS and body mass index (BMI). One hundred twenty RA patients were enrolled.
      MetS was assessed according to Adult Treatment Panel III criteria. All patients
      with known confounders influencing Vit D serum levels were excluded. Serum value
      of 25-hydroxyvitamin D (25(OH)D) was measured using a commercial ELISA kit. Data
      were analyzed by SPSS software. A logistic regression analysis stated that
      prednisolone dosage [p = 0.028, beta = 0.177, odds ratio (OR) = 1.194, confidence
      interval (CI, 1.09-1.32)], age [p = 0.002, beta = 0.146, OR = 1.57, CI (1.05
      1.27)] and Vit D serum levels [p = 0.049, beta = -3.766, OR = 0.023, CI (0.001
      0.978)] are all significant predictors of MetS occurrence in RA patients. It was
      shown that 25(OH)D is a protective factor against MetS. It was also shown that
      there is a negative correlation between BMI and 25(OH)D serum levels (P = 0.037,
      r (s) = -0.266). In summary, this study suggested that 25(OH)D plays a protective
      role against MetS in RA patients. However, this cross-sectional study did not
      permit a power calculation on the causal relationship between Vit D and metabolic
      syndrome. On the other hand, Vit D has a negative correlation with BMI in these
      patients.

PMID- 22581278
TI  - A randomized controlled trial of 8-form Tai chi improves symptoms and functional
      mobility in fibromyalgia patients.
AB  - Previous researchers have found that 10-form Tai chi yields symptomatic benefit
      in patients with fibromyalgia (FM). The purpose of this study was to further
      investigate earlier findings and add a focus on functional mobility. We conducted
      a parallel-group randomized controlled trial FM-modified 8-form Yang-style Tai
      chi program compared to an education control. Participants met in small groups
      twice weekly for 90 min over 12 weeks. The primary endpoint was symptom reduction
      and improvement in self-report physical function, as measured by the Fibromyalgia
      Impact Questionnaire (FIQ), from baseline to 12 weeks. Secondary endpoints
      included pain severity and interference (Brief Pain Inventory (BPI), sleep
      (Pittsburg sleep Inventory), self-efficacy, and functional mobility. Of the 101
      randomly assigned subjects (mean age 54 years, 93 % female), those in the Tai chi
      condition compared with the education condition demonstrated clinically and
      statistically significant improvements in FIQ scores (16.5 vs. 3.1, p = 0.0002),
      BPI pain severity (1.2 vs. 0.4, p = 0.0008), BPI pain interference (2.1 vs. 0.6,
      p = 0.0000), sleep (2.0 vs. -0.03, p = 0.0003), and self-efficacy for pain
      control (9.2 vs. -1.5, p = 0.0001). Functional mobility variables including timed
      get up and go (-.9 vs. -.3, p = 0.0001), static balance (7.5 vs. -0.3, p   
      0.0001), and dynamic balance (1.6 vs. 0.3, p = 0.0001) were significantly
      improved with Tai chi compared with education control. No adverse events were
      noted. Twelve weeks of Tai chi, practice twice weekly, provided worthwhile
      improvement in common FM symptoms including pain and physical function including
      mobility. Tai chi appears to be a safe and an acceptable exercise modality that
      may be useful as adjunctive therapy in the management of FM patients.
      (ClinicalTrials.gov Identifier, NCT01311427).

PMID- 22581279
TI  - Expression of prostaglandin F receptor in scleral and subconjunctival tissue.

PMID- 22581280
TI  - Epimacular membrane secondary to an optic nerve head lesion.

PMID- 22581281
TI  - Palladium(II) acetate mediated oxidative cyclization of omega-unsaturated alpha
      cyano ketones for facile construction of methylenecyclohexane ring system.
AB  - A highly efficient annulative approach towards the construction of the
      structurally attractive methylenecyclohexane ring was developed through a
      convenient 1,4-addition of 4-pentenylmagnesium bromide to 2-cyano-2
      cycloalkenones followed by a Pd(II)-mediated oxidative cyclization of the
      resulting omega-unsaturated alpha-cyano ketones. Based on this newly developed
      protocol, polycyclic adducts bearing various ring sizes and substitutions can be
      prepared in moderate to high yields.

PMID- 22581282
TI  - Incidence of venous thromboembolism among chemotherapy-treated patients with lung
      cancer and its association with mortality: a retrospective database study.
AB  - Cancer patients, especially those with lung cancer and undergoing chemotherapy,
      have an elevated risk for venous thromboembolism (VTE). This study assessed
      incidence, timing, and risk factors for VTE (specifically receipt of
      chemotherapy), along with the association between VTE and survival among lung
      cancer patients receiving chemotherapy. Using Florida Medicaid administrative
      claims data (2000-2008), patients with any diagnosis of primary lung cancer were
      selected. Patients with recent prior VTE and those enrolled in Medicare or an HMO
      were excluded. Crude rates of VTE per 100 person years were estimated, and Cox
      proportional hazards models were developed to assess risk factors for VTE in the
      lung cancer population, and the association between VTE and survival among
      patients undergoing chemotherapy. Of 15,749 lung cancer patients, 7,052 (2,242
      receiving chemotherapy and 4,810 not receiving chemotherapy) met cohort selection
      criteria. The incidence of VTE was 10.8 per 100 person-years (PYs) in the
      chemotherapy cohort and 6.8 per 100 PYs in the non-chemotherapy cohort. Among
      patients on chemotherapy developing VTE, median time to occurrence was 109 days,
      with 61 and 82 % of patients experiencing an event within six and 12 months,
      respectively. In multivariate analyses, the adjusted risk of VTE was 30 % higher
      among patients undergoing chemotherapy. Comorbidity and the presence of a central
      venous catheter also were significantly associated with a greater risk of
      developing VTE. Moreover, patients in the chemotherapy cohort who developed VTE
      had a significantly faster time-to-death (adjusted hazard ratio [HR] = 1.97; 95 %
      CI 1.69-2.29).VTE was common among lung cancer patients, especially among
      patients receiving chemotherapy, with the majority of VTE events occurring within
      6 months of initiation of chemotherapy. The presence of a VTE event was
      significantly associated with an increased risk of mortality.

PMID- 22581283
TI  - The ABCs of left ventricular assist device echocardiography: a systematic
      approach.
AB  - Echocardiography is an important imaging modality used to determine the
      indication of left ventricular assist device (LVAD) implantation for patients
      with advanced heart failure (HF) and for serial follow-up to make management
      decisions in patient care post-implant. Continuous axial-flow LVAD therapy
      provides effective haemodynamic support for the failing left ventricle, improving
      both the clinical functional status and quality of life. Echocardiographers must
      develop a systematic approach to echocardiographic assessment of LVAD
      implantation and post-LVAD implant cardiac morphology and physiology. This
      approach must include the evaluation of left and right heart chamber morphology
      and physiology and the anatomy and physiology of the inflow and outflow cannulas
      and the rotor pump, and the determination of the degree of tricuspid
      regurgitation and the presence of interatrial shunts and aortic regurgitation.
      Collaboration among the echocardiography and HF/transplant teams is essential to
      obtain this comprehensive evaluation. We outline a systematic approach to
      evaluating patients with HF who have failed conventional therapy and require LVAD
      therapy as a bridge to cardiac transplantation or destination therapy.

PMID- 22581284
TI  - Incremental value of three-dimensional strain imaging in Danon disease.

PMID- 22581285
TI  - Methylglyoxal modification of Nav1.8 facilitates nociceptive neuron firing and
      causes hyperalgesia in diabetic neuropathy.
AB  - This study establishes a mechanism for metabolic hyperalgesia based on the
      glycolytic metabolite methylglyoxal. We found that concentrations of plasma
      methylglyoxal above 600 nM discriminate between diabetes-affected individuals
      with pain and those without pain. Methylglyoxal depolarizes sensory neurons and
      induces post-translational modifications of the voltage-gated sodium channel
      Na(v)1.8, which are associated with increased electrical excitability and
      facilitated firing of nociceptive neurons, whereas it promotes the slow
      inactivation of Na(v)1.7. In mice, treatment with methylglyoxal reduces nerve
      conduction velocity, facilitates neurosecretion of calcitonin gene-related
      peptide, increases cyclooxygenase-2 (COX-2) expression and evokes thermal and
      mechanical hyperalgesia. This hyperalgesia is reflected by increased blood flow
      in brain regions that are involved in pain processing. We also found similar
      changes in streptozotocin-induced and genetic mouse models of diabetes but not in
      Na(v)1.8 knockout (Scn10(-/-)) mice. Several strategies that include a
      methylglyoxal scavenger are effective in reducing methylglyoxal- and diabetes
      induced hyperalgesia. This previously undescribed concept of metabolically driven
      hyperalgesia provides a new basis for the design of therapeutic interventions for
      painful diabetic neuropathy.

PMID- 22581287
TI  - NF-kappaB-inducing kinase (NIK) promotes hyperglycemia and glucose intolerance in
      obesity by augmenting glucagon action.
AB  - The canonical inhibitor of nuclear factor kappaB kinase subunit beta (IKK-beta)
      nuclear factor of kappa light polypeptide gene enhancer in B cells 1 (NF-kappaB1)
      pathway has been well documented to promote insulin resistance; however, the
      noncanonical NF-kappaB-inducing kinase (NIK)-NF-kappaB2 pathway is not well
      understood in obesity. Additionally, the contribution of counter-regulatory
      hormones, particularly glucagon, to hyperglycemia in obesity is unclear. Here we
      show that NIK promotes glucagon responses in obesity. Hepatic NIK was abnormally
      activated in mice with dietary or genetic obesity. Systemic deletion of Map3k14,
      encoding NIK, resulted in reduced glucagon responses and hepatic glucose
      production (HGP). Obesity is associated with high glucagon responses, and liver
      specific inhibition of NIK led to lower glucagon responses and HGP and protected
      against hyperglycemia and glucose intolerance in obese mice. Conversely,
      hepatocyte-specific overexpression of NIK resulted in higher glucagon responses
      and HGP. In isolated mouse livers and primary hepatocytes, NIK also promoted
      glucagon action and glucose production, at least in part by increasing cAMP
      response element-binding (CREB) stability. Therefore, overactivation of liver NIK
      in obesity promotes hyperglycemia and glucose intolerance by increasing the
      hyperglycemic response to glucagon and other factors that activate CREB.

PMID- 22581286
TI  - ApoB-containing lipoproteins regulate angiogenesis by modulating expression of
      VEGF receptor 1.
AB  - Despite the clear major contribution of hyperlipidemia to the prevalence of
      cardiovascular disease in the developed world, the direct effects of lipoproteins
      on endothelial cells have remained obscure and are under debate. Here we report a
      previously uncharacterized mechanism of vessel growth modulation by lipoprotein
      availability. Using a genetic screen for vascular defects in zebrafish, we
      initially identified a mutation, stalactite (stl), in the gene encoding
      microsomal triglyceride transfer protein (mtp), which is involved in the
      biosynthesis of apolipoprotein B (ApoB)-containing lipoproteins. By manipulating
      lipoprotein concentrations in zebrafish, we found that ApoB negatively regulates
      angiogenesis and that it is the ApoB protein particle, rather than lipid moieties
      within ApoB-containing lipoproteins, that is primarily responsible for this
      effect. Mechanistically, we identified downregulation of vascular endothelial
      growth factor receptor 1 (VEGFR1), which acts as a decoy receptor for VEGF, as a
      key mediator of the endothelial response to lipoproteins, and we observed VEGFR1
      downregulation in hyperlipidemic mice. These findings may open new avenues for
      the treatment of lipoprotein-related vascular disorders.

PMID- 22581288
TI  - A note on Cudrania cochinchinensis.

PMID- 22581289
TI  - Preoperative carbohydrate loading for elective surgery: a systematic review and
      meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: It is unclear whether the preoperative administration
      of oral carbohydrates (CHO) is safe and effective, and therefore we herein
      evaluated the efficacy and adverse events associated with CHO for elective
      surgery. METHODS: Comprehensive searches were conducted to identify randomized
      controlled trials (RCTs), which evaluated preoperative CHO for elective surgery.
      Two reviewers independently selected the trials, extracted data, and assessed the
      methodological qualities and evidence levels. The data were analyzed by the
      RevMan 5.0 software program. RESULT: CHO increased the insulin and glucose levels
      on the first day after surgery higher than those in overnight fasting group
      (fifteen RCTs) and i.v. glucose infusion group (three RCTs). The pooled results
      of thirteen RCTs showed greater declines in the insulin level at the induction of
      anesthesia and a smaller increase in the glucose level at the end of surgery, and
      fewer decreases in the postoperative insulin sensitivity index in the CHO group
      were observed as compared to the placebo group. No aspiration was observed in any
      of the included studies. CONCLUSION: CHO appears to be safe, and may attenuate
      postoperative insulin resistance as compared to placebo. However, the quality of
      most of the published trials has been poor, and the evidence levels for most
      outcomes were low, so rigorous and larger RCTs are needed in the future.

PMID- 22581291
TI  - Lack of response to teriparatide therapy for bisphosphonate-associated
      osteonecrosis of the jaw: reply to Subramanian and Quek.

PMID- 22581290
TI  - Comment on Narvaez et al.: lack of response to teriparatide therapy for
      bisphosphonate-associated osteonecrosis of the jaw.

PMID- 22581292
TI  - Does frequency of resistance training affect tibial cortical bone density in
      older women? A randomized controlled trial.
AB  - SUMMARY: This randomized controlled trial evaluated the effect of resistance
      training frequency (0, 1, and 2 times/week) on cortical volumetric bone mineral
      density (vBMD) at the tibia in older women. There was no mean difference in
      change in tibial cortical vBMD in older women who engaged in resistance training
      (RT) one or two times/week compared with the control group over 12 months after
      adjusting for baseline values. INTRODUCTION: National guidelines recommend RT two
      to three times/week to optimize bone health. Our objective was to determine the
      effect of a 12-month intervention of three different RT frequencies on tibial
      volumetric cortical density (CovBMD) in healthy older women. METHODS: We
      randomized participants to the following groups: (1) 2*/week balance and tone
      group (i.e., no resistance beyond body weight, BT), (2) 1*/week RT (RT1), and (3)
      2*/week RT (RT2). Treatment allocation was concealed, and measurement team and
      the bone data analyst were blinded to group allocation. We used peripheral
      quantitative computed tomography to acquire one 2.3-mm scan at the 50 % tibia,
      and the primary outcome was CovBMD. Data were collected at baseline, 6 and 12
      months, and we used linear mixed modeling to assess the effect at 12 months.
      RESULTS: We assessed 147 participants; 100 women provided data at all three
      points. Baseline unadjusted mean (SD) tibial CovBMD (in milligrams per cubic
      centimeter) at the 50 % site was 1,077.4 (43.0) (BT), 1,087.8 (42.0) (RT1), and
      1,058.7 (60.4) (RT2). At 12 months, there were no statistically significant
      differences (-0.45 to -0.17 %) between BT and RT groups for mean difference in
      change in tibial CovBMD for exercise interventions (BT, RT1, RT2) after adjusting
      for baseline tibial CovBMD. CONCLUSION: We note no mean difference in change in
      tibial CovBMD in older women who engaged in RT one or two times/week compared
      with the control group over 12 months. It is unknown if RT of 3* or 4*/week would
      be enough to promote a statistically significant difference in change of bone
      density.

PMID- 22581293
TI  - Significant inverse relationship between serum undercarboxylated osteocalcin and
      glycemic control in maintenance hemodialysis patients.
AB  - SUMMARY: Increased levels of serum undercarboxylated osteocalcin, which were
      associated with bone metabolism markers, correlated inversely with indices of
      glucose metabolism (plasma glucose, hemoglobin A1C, and glycated albumin) in
      hemodialysis patients with abnormalities of bone metabolism. INTRODUCTION:
      Undercarboxylated osteocalcin (ucOC), a possible marker of bone metabolism and
      one of the osteoblast-specific secreted proteins, has recently been reported to
      be associated with glucose metabolism. We tested the hypothesis that ucOC levels
      are associated with indices of glucose metabolism in chronic hemodialysis
      patients with abnormalities of bone metabolism. METHODS: Serum ucOC, bone
      alkaline phosphatase (BAP, a bone formation marker), and tartrate-resistant acid
      phosphatase-5b (TRACP-5b, a bone resorption marker) were measured in 189
      maintenance hemodialysis patients (96 diabetics and 93 non-diabetics), and their
      relationships with glucose metabolism were examined. RESULTS: ucOC correlated
      positively with BAP (rho = 0.489, p < 0.0001), TRACP-5b (rho = 0.585, p < 0.0001)
      and intact parathyroid hormone (iPTH; rho = 0.621, p < 0.0001). Serum ucOC levels
      in the diabetic patients were lower than those of non-diabetic patients (p <
      0.001), although there were no significant differences in serum BAP or TRACP-5b
      between diabetic and non-diabetic patients. Serum ucOC correlated negatively with
      plasma glucose (rho = -0.303, p < 0.0001), hemoglobin A1C (rho = -0.214, p <
      0.01), and glycated albumin (rho = -0.271, p < 0.001), although serum BAP or
      TRACP-5b did not. In multiple linear regression analysis, log [plasma glucose],
      log [hemoglobin A1C], and log [glycated albumin] were associated significantly
      with log [ucOC] after adjustment for age, gender, hemodialysis duration, and body
      mass index but were not associated with log [BAP], log [TRACP-5b], or log [intact
      PTH]. CONCLUSION: Increased levels of serum ucOC, which were associated with bone
      metabolism markers, were inversely associated with indices of glucose metabolism
      in hemodialysis patients.

PMID- 22581294
TI  - Differences in regional bone metabolism at the spine and hip: a quantitative
      study using (18)F-fluoride positron emission tomography.
AB  - SUMMARY: This study showed that regional bone blood flow and (18)F-fluoride bone
      plasma clearance measured by positron emission tomography are three times lower
      at the hip than the lumbar spine. INTRODUCTION: Measurements of effective bone
      plasma flow (K (1)), bone plasma clearance (K ( i )) and standardised uptake
      values (SUV) using (18)F-fluoride positron emission tomography ((18)F-PET)
      provide a useful means of studying regional bone metabolism at different sites in
      the skeleton. This study compares the regional (18)F-fluoride kinetics and SUV at
      the hip and lumbar spine (LS). METHODS: Twelve healthy postmenopausal women with
      no history of metabolic bone disease apart from two with untreated osteoporosis
      were recruited. Each subject underwent 60-min dynamic (18)F-PET scans at the LS
      and proximal femur two weeks apart. K (1), K ( i ) and SUV were measured at the
      LS (mean of L(1)-L(4)), femoral neck (FN), total hip (TH) and femoral shaft (FS).
      Differences between sites were assessed using the nonparametric Kruskal-Wallis
      test with a Bonferroni correction for multiple comparisons. RESULTS: Values of K
      (1), K ( i ) and SUV at the FN, TH and FS were three times lower than at the LS
      (p = 0.003). Amongst the proximal femur sites, K ( i ) and SUV were lower at the
      FS compared with the FN and TH, and SUV was lower at the TH compared with the FN
      (all p < 0.05). The volume of distribution was lower at the TH and FS compared
      with the LS (p < 0.05). CONCLUSION: The lower values of K (1), K ( i ) and SUV at
      the hip suggest that lower bone blood flow in the proximal femur is an important
      factor explaining the principal reason for the differences in bone fluoride
      kinetics between the LS and hip sites.

PMID- 22581295
TI  - Is bone microarchitecture status of the lumbar spine assessed by TBS related to
      femoral neck fracture? A Spanish case-control study.
AB  - Bone mineral density (BMD) as assessed by dual energy X-ray absorptiometry (DXA)
      constitutes the gold standard for osteoporosis diagnosis. However, DXA does not
      take into account bone microarchitecture alterations. INTRODUCTION: The aim of
      our study was to evaluate the ability of trabecular bone score (TBS) at lumbar
      spine to discriminate subjects with hip fracture. METHODS: We presented a case
      control study of 191 Spanish women aged 50 years and older. Women presented
      transcervical fractures only. BMD was measured at lumbar spine (LS-BMD) using a
      Prodigy densitometer. TBS was calculated directly on the same spine image.
      Descriptive statistics, tests of difference and univariate and multivariate
      backward regressions were used. Odds ratio (OR) and the ROC curve area of
      discriminating parameters were calculated. RESULTS: The study population
      consisted of 83 subjects with a fracture and 108 control subjects. Significant
      lower spine and hip BMD and TBS values were found for subjects with fractures (p
      < 0.0001). Correlation between LS-BMD and spine TBS was modest (r = 0.41, p <
      0.05). LS-BMD and TBS independently discriminate fractures equally well (OR =
      2.21 [1.56-3.13] and 2.05 [1.45-2.89], respectively) but remain lower than BMD at
      neck or at total femur (OR = 5.86 [3.39-10.14] and 6.06 [3.55-10.34],
      respectively). After adjusting for age, LS-BMD and TBS remain significant for
      transcervical fracture discrimination (OR = 1.94 [1.35-2.79] and 1.71 [1.15
      2.55], respectively). TBS and LS-BMD combination (OR = 2.39[1.70-3.37]) improved
      fracture risk prediction by 25 %. CONCLUSION: This study shows the potential of
      TBS to discriminate subjects with and without hip fracture. TBS and LS-BMD
      combination improves fracture risk prediction. Nevertheless, BMD at hip remains
      the best predictor of hip fracture.

PMID- 22581296
TI  - Impaired bone mineralization accompanied by low vitamin D and secondary
      hyperparathyroidism in patients with femoral neck fracture.
AB  - SUMMARY: Although it is well established that a decrease in bone mass increases
      the risk of osteoporotic fractures, the proportion of fractures attributable to
      areal bone mineral density (BMD) is rather low. Here, we have identified bone
      mineralization defects together with low serum 25-hydroxyvitamin D (25-(OH) D)
      levels as additional factors associated with femoral neck fractures.
      INTRODUCTION: Osteoporotic fractures of the femoral neck are associated with
      increased morbidity and mortality. Although it is well established that a
      decrease in bone mass increases the risk of osteoporotic fractures, the
      proportion of fractures attributable to areal BMD is rather low. To identify
      possible additional factors influencing femur neck fragility, we analyzed
      patients with femoral neck fracture. METHODS: We performed a detailed clinical
      and histomorphometrical evaluation on 103 patients with femoral neck fracture
      including dual-energy X-ray absorptiometry, laboratory parameters, and
      histomorphometric and bone mineral density distribution (BMDD) analyses of
      undecalcified processed biopsies of the femoral head and set them in direct
      comparison to skeletal healthy control individuals. RESULTS: Patients with
      femoral neck fracture displayed significantly lower serum 25-(OH) D levels and
      increased serum parathyroid hormone (PTH) compared to controls. Histomorphometric
      analysis revealed not only a decreased bone volume and trabecular thickness in
      the biopsies of the patients, but also a significant increase of osteoid indices.
      BMDD analysis showed increased heterogeneity of mineralization in patients with
      femoral neck fracture. Moreover, patients with femoral neck fracture and serum 25
      (OH) D levels below 12 MUg/l displayed significantly thinner trabecular bone.
      CONCLUSION: Taken together, our data suggest that impaired bone mineralization
      accompanied by low serum 25-(OH) D levels is of major importance in the etiology
      of femoral neck fractures. Therefore, balancing serum 25-(OH) D levels and
      thereby normalizing PTH serum levels may counteract pronounced mineralization
      defects and might decrease the incidence of femoral neck fractures.

PMID- 22581297
TI  - Acaricidal activity of the essential oils from three Lamiaceae plant species on
      Rhipicephalus turanicus Pom. (Acari: Ixodidae).
AB  - Acaricidal effects of three Labiatae essential oils extracted from ariel parts of
      Thymus sipyleus Boiss. subsp. sipyleus, Mentha longifolia L., and Dorystoechas
      hastata Boiss. & Heldr. ex Bentham on 10-day-old Rhipicephalus turanicus Pom.
      (Acari: Ixodidae) larvae were evaluated by using the larval packet test bioassay.
      Serial dilutions of the three essential oils were tested from a starting
      concentration of 1-0.1% (1.0, 0.5, 0.25, and 0.1% w/v). Results showed that all
      essential oils had very similar activity, producing complete mortality (100%) in
      all tested concentrations on 10-day-old R. turanicus tick larvae.

PMID- 22581298
TI  - Is the micro-agar larval development test reliable enough to detect ivermectin
      resistance?
AB  - To aid the diagnosis of anthelmintic resistance, a range of in vivo and in vitro
      techniques have been developed. Amongst in vitro techniques, the larval
      development test is the most widely employed. Six lambs were infected with
      susceptible (three) and ivermectin-resistant (three) isolates of Haemonchus
      contortus. The micro-agar larval development test (MALDT) was able to easily
      distinguish between susceptible and resistant isolates. Different proportions of
      resistant and susceptible eggs were subsequently incubated, i.e. development to
      the third larval stage occurred only in the resistant isolate. The percentage of
      resistant eggs ranged from 2 to 20.0 % of all eggs in the wells. In all cases,
      the MALDT was able to detect the presence of a minimum of 10 % of resistant worms
      amongst a susceptible background population. The probability was approximately 87
      % of positively diagnosing a proportion of resistant worms of only 2-4 % within
      the population.

PMID- 22581299
TI  - A prospective, randomised trial of transapical transcatheter aortic valve
      implantation vs. surgical aortic valve replacement in operable elderly patients
      with aortic stenosis: the STACCATO trial.
AB  - AIMS: In a prospective randomised trial we aimed to compare transapical
      transcatheter aortic valve implantation (a-TAVI) with surgical aortic valve
      replacement (SAVR) in operable elderly patients. METHODS AND RESULTS: The study
      was designed as a randomised controlled trial of a-TAVI (Edwards SAPIEN heart
      valve system; Edwards Lifesciences, Irvine, CA, USA) vs. SAVR. Operable patients
      with isolated aortic valve stenosis and an age >=75 years were included. The
      primary endpoint was the composite of all-cause mortality, cerebral stroke and/or
      renal failure requiring haemodialysis at 30 days. After advice from the Data
      Safety Monitoring Board, the study was prematurely terminated after the inclusion
      of 70 patients because of an excess of events in the a-TAVI group. The primary
      endpoint was met in five a-TAVI patients (two deaths, two strokes, and one case
      of renal failure requiring dialysis) vs. one stroke in the SAVR group (p=0.07).
      In the a-TAVI group, one patient was converted to SAVR because of an abnormally
      positioned heart, and four patients were re-operated with open heart surgery
      because of annulus rupture (n=1), severe paravalvular leakage (n=2), and blockage
      of the left coronary artery (n=1). In the SAVR group, one patient was converted
      to TAVI because of a large intra-thoracic goitre. CONCLUSIONS: Given the
      limitations of a small prematurely terminated study, our results suggest that a
      TAVI in its present form may be associated with complications and device success
      rates in low-risk patients similar or even inferior to those found in high-risk
      patients with aortic valve stenosis. This will probably change in the near future
      with improved catheter based devices and better pre-procedural assessment.

PMID- 22581300
TI  - Promoter methylation of RASSF1A modulates the effect of the microtubule-targeting
      agent docetaxel in breast cancer.
AB  - Docetaxel is one of the most commonly used chemotherapeutic agents in breast
      cancer. To avert from significant toxicities with no clinical benefit,
      identification of predictive markers for response is one of the most important
      unsolved clinical needs. Therefore, the potential associations of RASSF1A
      hypermethylation and response to docetaxel-based chemotherapy were evaluated, and
      the underlying mechanism was studied. The expression of RASSF1A in breast cancer
      cell lines and tissues of normal breast, ductal carcinoma in situ (DCIS), and
      breast cancer (n=45) was analyzed by immunohistochemistry and western blot
      analysis. Immunohistochemical staining showed that the expression of RASSF1A was
      frequently lost in primary breast cancers and human breast cancer cell lines,
      while normal breast tissues or DCIS displayed moderate to strong expression.
      Furthermore, quantitative methylation analysis of the RASSF1A promoter region in
      45 primary breast cancers revealed that RASSF1A was frequently methylated in
      primary breast cancers (>=20% methylation in 53% of the patients), and
      prospective analysis in patients with locally advanced or recurrent breast cancer
      showed that the mean level of methylation of RASSF1A was significantly higher in
      patients who did not respond to docetaxel-based chemotherapy (30.6+/-8.5%) than
      patients with partial or complete response (20.1+/-11.2%, p=0.042). Finally, in
      vitro studies showed that RASSF1A had cooperative activity in suppression of
      cancer cell growth and proliferation by enhancing docetaxel-induced cell cycle
      arrest. Our results suggest that hypermethylated RASSF1A is an important
      modulating factor for the efficacy of docetaxel-based chemotherapy in breast
      cancer.

PMID- 22581301
TI  - Clinical perspective: statins and the liver--harmful or helpful?

PMID- 22581302
TI  - A mystery wrapped in an enigma: Matrigel enhancement of mammary cell growth and
      morphogenesis.
AB  - The analysis of normal mammary morphogenesis is facilitated by the use of mammary
      fat pad transplantation. The recent experiments on analysis of normal mammary
      epithelial stem cell activity rely heavily on this technique. In this review, we
      discuss the known and unknown attributes of using Matrigel in the injection of
      the mammary epithelial cell suspension. Matrigel greatly increases the "take"
      frequency of the injected cell suspension; however, there is some uncertainty
      regarding the interpretation of some of the results. After consideration of these
      issues, our conclusion is that Matrigel is important in order to obtain rigorous
      and reproducible results.

PMID- 22581303
TI  - Saccade movements effect on the intravitreal drug delivery in vitreous
      substitutes: a numerical study.
AB  - In this study, the distributions of intravitreal injected drugs in post
      vitrectomy human eyes, which are subjected to periodic saccade movements, are
      investigated. The computational model for the vitreous cavity of human eye is a
      sphere with one side truncated by the eye lens. A dynamic mesh technique was used
      to model the eye motion and the unsteady 3-D forms of continuity; Navier-Stokes
      and concentration transport of drug equations were solved numerically. The
      numerical model was validated earlier for the vitreous liquid flow field. The
      predicted drug concentration for idealized geometry was compared with the
      available analytic solution and excellent agreement was observed. The validated
      computer model was then used to simulate a real vitreous cavity filled with
      Balanced Salt Solution or aqueous humor as a vitreous substitute in order to
      obtain distribution of drugs in the post-vitrectomy eyes or liquefied vitreous.
      Additionally, effects of locations of drug injection, drug diffusion coefficients
      and saccade amplitude on the drug distribution and its uniformity were
      investigated. Although the earlier findings in the literature reported a day or a
      week as a needed time for drug uniform distribution in the vitreous substitutes,
      the present work depicts that saccade movements augment the transport of the drug
      in a way that the uniformity of the drug distribution can be achieved in a matter
      of minutes. Furthermore, in a vitreous cavity subjected to the saccade movements,
      the diffusion coefficient of drugs does not significantly affect their
      distribution after a few minutes. Even the injection location does not matter as
      uniform distribution is achieved after some time.

PMID- 22581305
TI  - Bioelectromagnetic forward problem: isolated source approach revis(it)ed.
AB  - Electro- and magnetoencephalography (EEG and MEG) are non-invasive modalities for
      studying the electrical activity of the brain by measuring voltages on the scalp
      and magnetic fields outside the head. In the forward problem of EEG and MEG, the
      relationship between the neural sources and resulting signals is characterized
      using electromagnetic field theory. This forward problem is commonly solved with
      the boundary-element method (BEM). The EEG forward problem is numerically
      challenging due to the low relative conductivity of the skull. In this work, we
      revise the isolated source approach (ISA) that enables the accurate,
      computationally efficient BEM solution of this problem. The ISA is formulated for
      generic basis and weight functions that enable the use of Galerkin weighting. The
      implementation of the ISA-formulated linear Galerkin BEM (LGISA) is first
      verified in spherical geometry. Then, the LGISA is compared with conventional
      Galerkin and symmetric BEM approaches in a realistic 3-shell EEG/MEG model. The
      results show that the LGISA is a state-of-the-art method for EEG/MEG forward
      modeling: the ISA formulation increases the accuracy and decreases the
      computational load. Contrary to some earlier studies, the results show that the
      ISA increases the accuracy also in the computation of magnetic fields.

PMID- 22581306
TI  - Autologous cytokine-induced killer cell immunotherapy in lung cancer: a phase II
      clinical study.
AB  - OBJECTIVE: Cytokine-induced killer (CIK) cells have the ability to kill tumor in
      vitro and in vivo. This study was designed to evaluate the clinical efficacy of
      CIK cell immunotherapy following regular chemotherapy in patients with non-small
      cell lung cancer (NSCLC) after surgery. METHODS: A paired study, with 87 stage I
      IV NSCLC patients in each group, was performed. Patients received either
      chemotherapy (arm 2) or chemotherapy in combination with autologous CIK cell
      immunotherapy (arm 1). Progression-free survival (PFS) and overall survival (OS)
      were evaluated. RESULTS: Of the 87 paired patients, 50 had early-stage disease
      (stage I-IIIA) and 37 had advanced-stage disease (stage IIIB-IV). Among early
      stage patients, the distribution of 3-year PFS rate and median PFS time showed no
      statistical difference between the two groups (p = 0.259 and 0.093,
      respectively); however, the 3-year OS rate and median OS time in arm 1 were
      significantly higher than those in arm 2 (82 vs. 66 %; p = 0.049 and 73 vs. 53
      months; p = 0.006, respectively). Among the advanced-stage patients, the 3-year
      PFS and OS rates of arm 1 were significantly higher than those of arm 2 (6 vs. 3
      %; p < 0.001 and 31 vs. 3 %; p < 0.001, respectively); the median PFS and OS
      times in arm 1 were also significantly longer than those in arm 2 (13 vs. 6
      months; p = 0.001 and 24 vs. 10 months; p < 0.001, respectively). Multivariate
      analyses indicated that the frequency of CIK cell immunotherapy was significantly
      associated with prolonged PFS (HR = 0.91; 95 % CI 0.85-0.98; p = 0.012) and OS
      (HR = 0.83; 95 % CI, 0.74-0.93; p = 0.001) in the arm 1. CONCLUSIONS: The data
      suggested that CIK cell immunotherapy could improve the efficacy of conventional
      chemotherapy in NSCLC patients, and increased frequency of CIK cell treatment
      could further enhance the beneficial effects. A multi-center randomized trial is
      being carried out in our hospital to further validate these findings.

PMID- 22581304
TI  - The effect of biomaterials and antifungals on biofilm formation by Candida
      species: a review.
AB  - Candida albicans, C. glabrata, C. parapsilosis, and C. tropicalis are able to
      form biofilms on virtually any biomaterial implanted in a human host. Biofilms
      are a primary cause of mortality in immunocompromised and hospitalized patients,
      as they cause recurrent and invasive candidiasis, which is difficult to
      eradicate. This is due to the fact that the biofilm cells show high resistance to
      antifungal treatments and the host defense mechanisms, and exhibit an excellent
      ability to adhere to biomaterials. Elucidation of the mechanisms of antifungal
      resistance in Candida biofilms is of unquestionable importance; therefore, this
      review analyzes both the chemical composition of biomaterials used to fabricate
      the medical devices, as well as the Candida genes and proteins that confer drug
      resistance.

PMID- 22581307
TI  - Relationship between vision-related quality of life and different types of
      existing visual fields in Japanese patients.
AB  - To investigate the vision-related quality of life (VRQOL) in relation to the type
      of existing visual field (EVF) in the presence of visual field defect. We
      evaluated the VRQOL of 95 patients by using Visual Function Questionnaire-25 (NEI
      VFQ-25). Patients fulfilled the following criteria: (1) they underwent a Goldmann
      perimetry (GP) test within 3 months of the initial visit, (2) the results of the
      GP test could be classified into three categories, and (3) the best-corrected
      decimal visual acuity (VA) was <=0.3. The EVF was assessed by composite
      measurement of both eyes for the V-4e or I-4e isopters, as obtained using the GP
      test. We compared the VFQ-25 scores between three groups: (1) the "center and
      peripheral" group in which the EVF of the V-4e area was >30o and the I-4e area
      was <30o, (2) the "central VF" group in which the EVF of the V-4e area was <20o,
      and (3) the "central VF loss" group in which the central scotoma was >5o and the
      EVF of the V-4e area was >30o in peripheral vision. There were significant
      differences between the three groups (P = 0.02, ANOVA). The total score of the
      "central VF loss" group was significantly lower than those of the "center and
      peripheral" and "central VF" groups. The central vision influenced the VRQOL to a
      greater extent than peripheral vision.

PMID- 22581308
TI  - Implantable collamer lenses after intracorneal ring segments for keratoconus.
AB  - To report the clinical characteristics and visual outcomes of patients with
      keratoconus treated with posterior chamber phakic intraocular lenses after
      implantation of intracorneal ring segments (ICRS). This retrospective study
      included 11 eyes of eight patients diagnosed with keratoconus treated with ICRS
      and posterior chamber phakic intraocular lenses. The preoperative and
      postoperative uncorrected distance visual acuity (UDVA), corrected distance
      visual acuity (CDVA), preoperative and postoperative keratometric data, manifest
      refraction and spherical equivalent were recorded. No complications were
      observed. At 38.18 +/- 18.7 months of follow-up, the mean spherical error was 
      0.06 +/- 0.46 D (+0.75 to -0.75 D) and cylindrical error of -1.22 +/- 0.65 D (
      0.25 to -1.5 D). The preoperative spherical equivalent was -10.52 +/- 5.88 D (
      3.12 to -22.75 D) and the postoperative spherical equivalent was -0.68 +/- 0.45 D
      (0 to -1.25 D), p < 0.001. The preoperative and postoperative UDVA were 1.31 +/-
      0.37 logMAR (mean 20/400 Snellen, 0.69-1.77 logMAR) and 0.14 +/- 0.04 (mean 20/30
      Snellen, 0.09-0.47 logMAR), with a p value <0.001. The preoperative and
      postoperative CDVA were 0.289 +/- 0.14 logMAR (mean 20/40 Snellen, 0-0.477
      logMAR) and 0.16 +/- 0.08 (mean 20/25 Snellen, 0.09-0.39 logMAR), with a p value
      of 0.007. Combined treatment of keratoconus with ICRS and posterior chamber
      phakic intraocular lenses was a safe and effective procedure for high refractive
      errors induced by keratoconus in these selected patients.

PMID- 22581310
TI  - Strategies for the enantioselective synthesis of spirooxindoles.
AB  - Oxindoles and spirooxindoles are important synthetic targets that are often
      considered to be prevalidated with respect to their biological activity and
      applications for pharmaceutical lead discovery. This review features efficient
      strategies for the enantioselective synthesis of spirocyclic oxindoles, focusing
      on reports in 2010 and 2011. Although enantioselective synthesis remains an
      ongoing challenge, exciting recent advances in this area feature spirooxindoles
      with greater complexity, up to eight stereogenic centers, more practical
      synthetic methods, and new catalytic activation strategies. Developments in
      catalyst systems and reaction conditions have shown that many reactions can be
      optimized to control selectivity and provide access to isomeric products, which
      are important for biological testing. This review is organized based on two
      primary disconnection strategies, and then further subdivided into the type and
      ring size of the spirocycle that is generated. Strategies are also compared for
      the synthesis of non-spirocyclic 3,3'-disubstituted oxindoles.

PMID- 22581309
TI  - Carrageenan-induced transient inflammation in a rabbit knee model: molecular
      changes consistent with an early osteoarthritis phenotype.
AB  - OBJECTIVE: Inflammation following a knee injury is one of the factors associated
      with initiation of cartilage degeneration leading to osteoarthritis (OA). The
      hypothesis tested was that inflammation results in elevated expression of
      proteinases implicated in OA. METHODS: Mature female rabbits received a single
      carrageenan injection to the right hind knee and the left knee served as the
      control. Five animals were killed at time points of 1, 2 and 4 weeks. The
      synovium and cartilage from both knees were collected and analysed for specific
      mRNA levels. RESULTS: Interleukin (IL)-1beta and IL-6 mRNA levels peaked at 2
      weeks and returned to normal levels in tissues by 4 weeks post-carrageenan
      treatment. Matrix metalloproteinase (MMP)-13, MMP-1, MMP-3 and cathepsin K
      followed the trend set by the inflammatory cytokines. Both synovium and cartilage
      tissues exhibited similar patterns of molecular expression, with cartilage from
      the tibial plateau responding more strongly than the femoral condyles.
      CONCLUSIONS: The acute inflammatory milieu controls the transient expression of
      many degradative proteinases in the knee. However, a single acute exposure to
      inflammation in the rabbit knee is insufficient to create a chronic inflammatory
      environment and other complementary factors, such as persistent mechanical
      instability and/or injury, may contribute to the establishment of OA.

PMID- 22581311
TI  - Neuropathology and its meetings: a difficult relationship between evolving
      partners.

PMID- 22581312
TI  - A developmental study of the neural circuitry mediating motor inhibition in
      bipolar disorder.
AB  - OBJECTIVE: Despite increased interest in the developmental trajectory of the
      pathophysiology mediating bipolar disorder, few studies have compared adults and
      youths with bipolar disorder. Deficits in motor inhibition are thought to play an
      important role in the pathophysiology of the illness across the age spectrum. The
      authors compared the neural circuitry mediating this process in bipolar youths
      relative to bipolar adults and in healthy volunteers. METHOD: Participants were
      pediatric (N=16) and adult (N=23) patients with bipolar disorder and healthy
      child (N=21) and adult (N=29) volunteers. Functional MRI (fMRI) data were
      acquired while participants performed the stop-signal task. RESULTS: During
      failed inhibition, an age group-by-diagnosis interaction manifested in the
      anterior cingulate cortex, with bipolar youths exhibiting hypoactivation relative
      to both healthy youths and bipolar adults, and bipolar adults exhibiting
      hyperactivation relative to healthy adults. During successful inhibition, a main
      effect of diagnosis emerged in the right nucleus accumbens and the left ventral
      prefrontal cortex, with bipolar patients in both age groups showing less
      activation than healthy subjects. CONCLUSIONS: Anterior cingulate cortex
      dysfunction during failed motor inhibition was observed in both bipolar youths
      and adults, although the nature of this dysfunction differed between the two
      groups. Adults and youths with bipolar disorder exhibited similar deficits in
      activation of the nucleus accumbens and the ventral prefrontal cortex during
      successful inhibition. Therefore, while subcortical and ventral prefrontal cortex
      hypoactivation was present in bipolar patients across the lifespan, anterior
      cingulate cortex dysfunction varied developmentally, with reduced activation in
      youths and increased activation in adults during failed inhibition. Longitudinal
      fMRI studies of the developmental trajectory of the neural circuitry mediating
      motor inhibition in bipolar disorder are warranted.

PMID- 22581313
TI  - Blue-phase templated fabrication of three-dimensional nanostructures for photonic
      applications.
AB  - A promising approach to the fabrication of materials with nanoscale features is
      the transfer of liquid-crystalline structure to polymers. However, this has not
      been achieved in systems with full three-dimensional periodicity. Here we
      demonstrate the fabrication of self-assembled three-dimensional nanostructures by
      polymer templating blue phase I, a chiral liquid crystal with cubic symmetry.
      Blue phase I was photopolymerized and the remaining liquid crystal removed to
      create a porous free-standing cast, which retains the chiral three-dimensional
      structure of the blue phase, yet contains no chiral additive molecules. The cast
      may in turn be used as a hard template for the fabrication of new materials. By
      refilling the cast with an achiral nematic liquid crystal, we created templated
      blue phases that have unprecedented thermal stability in the range -125 to 125 
      degrees C, and that act as both mirrorless lasers and switchable electro-optic
      devices. Blue-phase templated materials will facilitate advances in device
      architectures for photonics applications in particular.

PMID- 22581314
TI  - A search model for topological insulators with high-throughput robustness
      descriptors.
AB  - Topological insulators (TI) are becoming one of the most studied classes of novel
      materials because of their great potential for applications ranging from
      spintronics to quantum computers. To fully integrate TI materials in electronic
      devices, high-quality epitaxial single-crystalline phases with sufficiently large
      bulk bandgaps are necessary. Current efforts have relied mostly on costly and
      time-consuming trial-and-error procedures. Here we show that by defining a
      reliable and accessible descriptor , which represents the topological robustness
      or feasibility of the candidate, and by searching the quantum materials
      repository aflowlib.org, we have automatically discovered 28 TIs (some of them
      already known) in five different symmetry families. These include peculiar
      ternary halides, Cs{Sn,Pb,Ge}{Cl,Br,I}(3), which could have been hardly
      anticipated without high-throughput means. Our search model, by relying on the
      significance of repositories in materials development, opens new avenues for the
      discovery of more TIs in different and unexplored classes of systems.

PMID- 22581315
TI  - Co-silencing of Birc5 (survivin) and Hspa5 (Grp78) induces apoptosis in hepatoma
      cells more efficiently than single gene interference.
AB  - Birc5 (previously known as survivin) is a cancer-specific protein. Due to the
      upregulation of its expression in various human malignancies and its key role in
      apoptosis, proliferation and angiogenesis, Birc5 has attracted attention as a
      target for anticancer therapies. In this study, when Birc5 was silenced in HepG2
      cells, 29.7+/-3.3% cells underwent apoptosis as expected. It was found that the
      expression levels of glucose-regulated protein 78 (Hspa5, previously known as
      Grp78) was increased by almost 3-fold in Birc5-silenced HepG2 cells. Hspa5, a
      master regulator of the anti-apoptotic unfolded protein response signalling
      network, can also promote tumor proliferation, survival and metastasis. Hence, we
      hypothesized that the co-silencing of Birc5 and Hspa5 may exert a stronger
      apoptosis-inducing effect than single gene interference. To verify this, the
      expression levels of Birc5 and Hspa5 in human hepatocellular carcinoma tissues
      were determined. Immunohistochemical staining showed that the expression of Birc5
      and Hspa5 was elevated in 28 out of 31 samples. Additionally, plasmid-based siRNA
      against Birc5 and/or Hspa5 were constructed and transfected into the human
      hepatocellular liver carcinoma cell line, HepG2. Compared with the HepG2 cells,
      in which Birc5 or Hspa5 were silenced alone, only 44.2+/-3.4% of the co-silenced
      cells proliferated, and 40.3+/-3.7% co-silenced cells underwent apoptosis
      (p<0.05). Furthermore, tumor formation from inoculated subcutaneous co-silenced
      cells in nude mice was inhibited significantly. The current study suggests that
      Birc5 and Hspa5 could be important survival factors for hepatoma carcinoma cells
      and that the simultaneous knockdown of Birc5 and Hspa5 is more effective in
      inducing apoptosis in HepG2 cells than the knockdown of Birc5 or Hspa5 alone. The
      co-silencing of Birc5 and Hspa5 could be warranted for cancer therapy.

PMID- 22581316
TI  - A serological survey of Akabane virus infection in cattle and sheep in northwest
      China.
AB  - PURPOSE: Akabane disease characterized mainly by fetal damage is a ruminant
      disease caused by insect-transmitted Akabane virus infection. METHODS: We
      investigated Akabane disease using serum neutralization tests in 446 blood
      samples collected from 187 cattle and 259 sheep of Xinjiang province, northwest
      China. RESULTS: (1) The overall prevalence rate of neutralizing antibody was
      19.06 % (85/446), (2) the prevalence rates of Akabane disease in cattle and sheep
      were 20.32 % (38/187) and 18.15 % (47/259), respectively, (3) the disease
      prevalence rates were not significantly different between cattle and sheep, but
      significantly different among samples collected from different sampling months,
      (4) the disease was most prevalent in July when mosquitoes and culicoides were
      most active, and (5) the disease prevalence rates were significantly different
      between individuals with abortion experience and without abortion experience (P <
      0.05), suggesting that Akabane virus infection may significantly increase
      abortion risk in cattle and sheep. CONCLUSIONS: To our knowledge, this is the
      first report confirming that Akabane virus infection is common in cattle and
      sheep of Xinjiang province, northwest China and providing useful epidemiological
      information for cattle and sheep abortion prevention and control.

PMID- 22581317
TI  - Patterns of religious coping among bereaved college students.
AB  - Contemporary research has suggested that bereavement is a paramount issue in
      college populations, a group which has historically been underrepresented in
      grief research (Balk. in Death studies 25:67-84, 2001; Balk et al. in Death
      Studies 34:459-468, 2010). Indeed, there has been a call to generate new research
      on grief with specific populations and age groups (Center for the Advancement of
      Health. in Death Studies 28:568-575, 2004). Religion is often described as a
      primary way that individuals cope with bereavement in particular (Frantz et al.
      in Pastor Psychol 44(3):151-163, 1996) and has been shown to effect college
      student reactions to stress in general (Merrill et al. in Mental Health, Religion
      & Culture 12(5):501-511, 2009). The RCOPE (Pargament et al. in J Clin Psychol
      56(4):519-543, 2000, J Health Psychol 9:713-730, 2004) is a frequently used
      measure of religious coping, but has not been evaluated with a bereaved
      undergraduate population. Given that emerging adulthood is a critical
      developmental phase of religious identity (Fowler. in New Directions for Child
      Development 3(52):27-45, 1991), the current study examined the factor structure
      of the RCOPE within a sample of bereaved college students. An exploratory factor
      analysis was performed, which approximated the factor structure proposed by
      Pargament et al. (J Clin Psychol 56(4):519-543, 2000). However, a high
      correlation between the positive and negative religious coping subscales (r =
      0.71) detracted from the predictive utility of Pargament et al.'s (2000) two
      overarching subscales. Therefore, an exploratory factor analysis with an
      orthogonal rotation was used to identify two uncorrelated subscales (adaptive
      religious coping and maladaptive religious coping). This new two-factor, 39-item
      version of the RCOPE was found to demonstrate good internal consistency (alpha >
      0.8) as well as convergent and discriminant validity. The interaction between
      religious coping strategies and core beliefs about the predictability of the
      world is explored, and directions for future research and clinical practice are
      suggested. 

PMID- 22581318
TI  - Post-mortem computed tomography and 3D imaging: anthropological applications for
      juvenile remains.
AB  - Anthropological examination of defleshed bones is routinely used in medico-legal
      investigations to establish an individual's biological profile. However, when
      dealing with the recently deceased, the removal of soft tissue from bone can be
      an extremely time consuming procedure that requires the presence of a trained
      anthropologist. In addition, due to its invasive nature, in some disaster victim
      identification scenarios the maceration of bones is discouraged by religious
      practices and beliefs, or even prohibited by national laws and regulations.
      Currently, three different radiological techniques may be used in the
      investigative process; plain X-ray, dental X-ray and fluoroscopy. However, recent
      advances in multi-detector computed tomography (MDCT) mean that it is now
      possible to acquire morphological skeletal information from high resolution
      images, reducing the necessity for invasive procedures. This review paper
      considers the possible applications of a virtual anthropological examination by
      reviewing the main juvenile age determination methods used by anthropologists at
      present and their possible adaption to MDCT.

PMID- 22581319
TI  - Fatal positional asphyxia.

PMID- 22581320
TI  - Secondary intraocular uveal involvement by primary paranasal sinus lymphoma.
AB  - To report an unusual case of primary paranasal sinus lymphoma associated with
      intraocular secondary uveal involvement. Retrospective case report emphasizing
      the histopathologic diagnosis as well as imaging studies, and review of the
      pertinent literature. The diagnosis of ophthalmologic lymphoma can be difficult
      due to the infrequency of the disease, the diverse presentation, and the need for
      biopsy for definitive diagnosis. Prior clinical history and systemic testing may
      be important confirmations in diagnosing such cases.

PMID- 22581321
TI  - Visual loss related to macular subretinal fluid and cystoid macular edema in HIV
      related optic neuropathy.
AB  - Optic nerve involvement may occur in various infectious diseases, but is rarely
      reported after infection by the human immunodeficiency virus (HIV). We report the
      atypical case of a 38-year-old patient in whom the presenting features of HIV
      infection were due to a bilateral optic neuropathy associated with macular
      subretinal fluid and cystoid macular edema, which responded well to
      antiretroviral therapy.

PMID- 22581322
TI  - Ocular surface squamous neoplasia in an immunosuppressed patient with atopic
      keratoconjunctivitis.
AB  - We describe a patient with severe atopic dermatitis and keratoconjunctivitis, who
      was prescribed both systemic and topical ciclosporin and who developed ocular
      surface squamous neoplasia (OSSN). To provide additional information on the
      incidence of the association between topical ciclosporin use and OSSN, we counted
      the total prescriptions for topical ciclosporin issued in our hospital between
      2003 and 2006 (804 patients) and, for the same period, we reviewed the records of
      patients with OSSN for a history of treatment with ciclosporin or a history of
      atopy. No other case of OSSN in a patient with a history of topical ciclosporin
      use was identified, which makes it difficult to implicate topical ciclosporin as
      the causative factor.

PMID- 22581324
TI  - Alfred Russel Wallace and the elimination of the unfit.

PMID- 22581323
TI  - Lymphohematopoietic licence: sterol C-14 reductase activity of lamin B receptor
      (Lbr) is essential for neutrophil differentiation.

PMID- 22581325
TI  - NR Moudgal - a pioneer in the development of immunocontraceptive approaches.

PMID- 22581326
TI  - From aneuploidy to cancer: the evolution of a new species?

PMID- 22581327
TI  - Molecular typing of fecal eukaryotic microbiota of human infants and their
      respective mothers.
AB  - The micro-eukaryotic diversity from the human gut was investigated using
      universal primers directed towards 18S rRNA gene, fecal samples being the source
      of DNA. The subjects in this study included two breast-fed and two formula-milk
      fed infants and their mothers. The study revealed that the infants did not seem
      to harbour any microeukaryotes in their gut. In contrast, there were distinct
      eukaryotic microbiota present in the mothers. The investigation is the first of
      its kind in the comparative study of the human feces to reveal the presence of
      micro-eukaryotic diversity variance in infants and adults from the Indian
      subcontinent. The micro-eukaryotes encountered during the investigation include
      known gut colonizers like Blastocystis and some fungi species. Some of these
      micro-eukaryotes have been speculated to  be involved in clinical manifestations
      of various diseases. The study is an attempt to highlight the importance of micro
      eukaryotes  in the human gut.

PMID- 22581328
TI  - Neuropeptide Y gene expression around meal time in the Brazilian flounder
      Paralichthys orbignyanus.
AB  - Neuropeptide Y (NPY) is considered the major stimulant for food intake in mammals
      and fish. Previous  results indicate that NPY is involved in the feeding
      behaviour of the Brazilian flounder, Paralichthys orbignyanus. In this study, we
      evaluated hypothalamic NPY expression before (-2 h), during (0 h) and after
      feeding (+2 h) in two independent experiments: (1) during a normal feeding
      schedule and (2) in fish fasted for 2 weeks. During normal feeding, changes in
      the levels of NPY mRNA were periprandial, with expression levels being
      significantly elevated at meal time (P less than 0.05) and significantly reduced
      2 h later (P less than 0.05). Comparing the fasting and unfasted groups, NPY mRNA
      levels were significantly higher (P less than 0.05) at -2 h and +2 h in the
      fasting group, but there was no difference at 0 h. In addition, the higher NPY
      mRNA levels that were observed in the fasting group were maintained throughout
      the sampling period. In summary, our results show that NPY expression was
      associated with meal time (0 h) in food intake regulation.

PMID- 22581329
TI  - Effect of LNA- and OMeN-modified oligonucleotide probes on the stability and
      discrimination of  mismatched base pairs of duplexes.
AB  - Locked nucleic acid (LNA) and 2'-O-methyl nucleotide (OMeN) are the most
      extensively studied nucleotide analogues. Although both LNA and OMeN are
      characterized by the C3'-endo sugar pucker conformation, which is dominant in A
      form DNA and RNA nucleotides, they demonstrate different binding behaviours.
      Previous studies have focused attention on their properties of duplex
      stabilities, hybridization kinetics and resistance against nuclease digestion;
      however, their ability to discriminate mismatched hybridizations has been
      explored much less. In this study, LNA- and OMeN-modified oligonucleotide probes
      have been prepared and their effects on the DNA duplex stability have been
      examined: LNA modifications can enhance the duplex stability, whereas OMeN
      modifications reduce the duplex stability. Next, we studied how the LNA:DNA and
      OMeN:DNA mismatches reduced the duplex stability. Melting temperature measurement
      showed that different LNA:DNA or OMeN:DNA mismatches indeed influence the duplex
      stability differently. LNA purines can discriminate LNA:DNA mismatches more
      effectively than LNA pyrimidines as well as DNA nucleotides. Furthermore, we
      designed five LNA- and five OMeN-modified oligonucleotide probes to simulate
      realistic situations where target-probe duplexes contain a complementary LNA:DNA
      or OMeN:DNA base pairs and a DNA:DNA mismatch simultaneously. The measured
      collective effect showed that the duplex stability was enhanced by the
      complementary LNA:DNA base pair but decreased by the DNA:DNA mismatch in a
      position-dependent manner regardless of the chemical identity and position of the
      complementary LNA:DNA base pair. On the other hand, the OMeN-modified probes also
      showed that the duplex stability was reduced by both the OMeN modification and
      the OMeN:DNA mismatch in a position-dependent manner.

PMID- 22581330
TI  - STAT3 mutations correlated with hyper-IgE syndrome lead to blockage of IL-6/STAT3
      signalling pathway.
AB  - Of all the causes identified for the disease hyper-immunoglobulinemia E syndrome
      (HIES), a homozygous  mutation in tyrosine kinase2 (TYK2) and heterozygous
      mutations in STAT3 are implicated the defects in Jak/STAT signalling pathway in
      the pathogenesis of HIES. Mutations of STAT3 have been frequently clinically
      identified in autosomaldominant (AD) HIES patients' cells, and therefore, the
      genotype of STAT3 has been associated with the phenotype of HIES. Here, we
      conducted studies on the functional loss of the seven specific STAT3 mutations
      correlated with ADHIES. Using STAT3-null human colon carcinoma cell line A4
      cells, we generated seven mutants of STAT3 bearing single mutations  clinically
      identified in AD-HIES patients' cells and studied the functional loss of these
      mutants in IL- 6-Jak/STAT3 signalling pathway. Our results show that five STAT3
      mutants bearing mutations in the DNA-binding domain maintain the phosphorylation
      of Tyr705 and the ability of dimerization while the other two with mutations in
      SH2 domain are devoid of the phosphorylation of Try705 and abrogate the
      dimerization in response to IL-6. The phosphorylation of Ser727 in these mutants
      shows diversity in response to IL-6. These mutations eventually converge on the
      abnormalities of the IL-6/Gp130/Jak2-mediated STAT3 transactivation on target
      genes, indicative of the dysregulation of JAK/STAT signalling present in HIES.

PMID- 22581331
TI  - Characterization of P1 promoter activity of the beta-galactoside alpha2,6
      sialyltransferase I gene  (siat 1) in cervical and hepatic cancer cell lines.
AB  - The level of beta-galactoside alpha2,6-sialyltransferase I (ST6Gal I) mRNA,
      encoded by the gene siat1,  is increased in malignant tissues. Expression is
      regulated by different promoters - P1, P2 and P3 - generating three mRNA isoforms
      H, X and YZ. In cervical cancer tissue the mRNA isoform H, which results from P1
      promoter activity, is increased. To study the regulation of P1 promoter,
      different constructs from P1 promoter were evaluated by luciferase assays in
      cervical and hepatic cell lines. Deletion of a fragment of 1048 bp (-89 to +24
      bp) increased 5- and 3-fold the promoter activity in C33A and HepG2 cell lines,
      respectively. The minimal region with promoter activity was a 37 bp fragment in
      C33A cells. The activity of this region does not require the presence of an
      initiator sequence. In HepG2 cells the minimal promoter activity was detected in
      the 66 bp fragment. Sp1 (-32) mutation increased the promoter activity only in
      HepG2 cells. HNF1 mutation decreased promoter activity in HepG2 cell line but not
      in C33A cells. We identified a large region that plays a negative regulation
      role. The regulation of promoter activity is cell type specific. Our study
      provides new insights into the complex transcriptional regulation of siat1 gene.

PMID- 22581332
TI  - In vivo and in vitro effect of Acacia nilotica seed proteinase inhibitors on
      Helicoverpa armigera (Hubner) larvae.
AB  - Acacia nilotica proteinase inhibitor (AnPI) was isolated by ammonium sulphate
      precipitation followed by  chromatography on DEAE-Sephadex A-25 and resulted in a
      purification of 10.68-fold with a 19.5 percentage yield. Electrophoretic analysis
      of purified AnPI protein resolved into a single band with molecular weight of
      approximately 18.6+1.00 kDa. AnPI had high stability at different pH values (2.0
      to 10.0) except at pH 5.0 and are thermolabile beyond 80 degree C for 10 min.
      AnPI exhibited effective against total proteolytic activity and trypsin-like
      activity, but did not show any inhibitory effect on chymotrypsin activity of
      midgut of Helicoverpa armigera. The inhibition kinetics studies against H.
      armigera gut trypsin are of non-competitive type. AnPI had low affinity for H.
      armigera gut trypsin when compared to SBTI. The partially purified and purified
      PI proteins-incorporated test diets showed significant reduction in mean larval
      and pupal weight of H. armigera. The results provide important clues in designing
      strategies by using the proteinase inhibitors (PIs) from the A. nilotica that can
      be expressed in genetically engineered plants to confer resistance to H.
      armigera.

PMID- 22581333
TI  - Quercetin modulates activities of Taiwan cobra phospholipase A2 via its effects
      on membrane structure and membrane-bound mode of phospholipase A2.
AB  - The goal of the present study is to elucidate the mechanism of quercetin on
      modulating Naja naja atra phospholipase A2 (PLA2) activities. Sphingomyelin
      inhibited PLA2 enzymatic activity and membrane-damaging activity against egg yolk
      phosphatidylcholine (EYPC), while cholesterol and quercetin abrogated the
      sphingomeyelin inhibitory effect. Quercetin incorporation led to a reduction in
      PLA2 enzymatic activity and membrane-damaging activity toward
      EYPC/sphingomyelin/cholesterol vesicles. Both cholesterol and quercetin increased
      detergent resistance and reduced membrane fluidity of EYPC/sphingomyelin
      vesicles. Quercetin reduced detergent insolubility but increased ordered lipid
      packing of EYPC/sphingomyelin/cholesterol vesicles. Acrylamide quenching studies
      and trinitrophenylation of Lys residues revealed that quercetin altered the
      membrane-bound mode of PLA2 differently upon absorption onto the membrane
      bilayers of different lipid compositions. However, 8-anilinonaphthalene
      sulphonate-binding assay revealed that quercetin marginally affected the
      interaction between active site of PLA2 with phospholipid vesicles. Collectively,
      our data indicate that membrane-inserted quercetin modulates PLA2 interfacial
      activity and membrane-damaging activity via its effects on membrane structure and
      membrane-bound mode of PLA2.

PMID- 22581334
TI  - Adipokine leptin in obesity-related pathology of breast cancer.

PMID- 22581335
TI  - Insights into eisosome assembly and organization.
AB  - Eisosomes, large protein complexes that are predominantly composed of BAR-domain
      containing proteins Pil1 and its homologs, are situated under the plasma membrane
      of ascomycetes. A successful targeting of Pil1 onto the future site of eisosome
      accompanies maturation of eisosome. During or after recruitment, Pil1 undergoes
      self-assembly into filaments that can serve as scaffolds to induce membrane
      furrows or invaginations. Although a consequence of the invagination is likely to
      redistribute particular proteins and lipids to a different location, the precise
      physiological role of membrane invagination and eisosome assembly awaits further
      investigation. The present review summarizes recent research findings within the
      field regarding the detailed structural and functional significance of Pil1 on
      eisosome organization.

PMID- 22581336
TI  - Nucleic acids in circulation: are they harmful to the host?
AB  - It has been estimated that 10(11) -10(12) cells, primarily of haematogenous
      origin, die in the adult human body daily, and a similar number is regenerated to
      maintain homeostasis. Despite the presence of an efficient scavenging system for
      dead cells, considerable amounts of fragmented genetic material enter the
      circulation in healthy individuals. Elevated blood levels of extracellular
      nucleic acids have been reported in various disease conditions; such as ageing
      and age-related degenerative disorders, cancer; acute and chronic inflammatory
      conditions, severe trauma and autoimmune disorders. In addition to genomic DNA
      and nucleosomes, mitochondrial DNA is also found in circulation, as are RNA and
      microRNA. There is extensive literature that suggests that extraneously added
      nucleic acids have biological actions. They can enter into cells in vitro and in
      vivo and induce genetic transformation and cellular and chromosomal damage; and
      experimentally added nucleic acids are capable of activating both innate and
      adaptive immune systems and inducing a sterile inflammatory response. The
      possibility as to whether circulating nucleic acids may, likewise, have
      biological activities has not been explored. In this review we raise the question
      as to whether circulating nucleic acids may have damaging effects on the host and
      be implicated in ageing and diverse acute and chronic human pathologies.

PMID- 22581337
TI  - Pyrroloquinoline-quinone and its versatile roles in biological processes.
AB  - Pyrroloquinoline-quinine (PQQ) was initially characterized as a redox cofactor
      for membrane-bound dehydrogenases in the bacterial system. Subsequently, PQQ was
      shown to be an antioxidant protecting the living cells from oxidative damage in
      vivo and the biomolecules from artificially produced reaction oxygen species in
      vitro. The presence of PQQ has been documented from different biological samples.
      It functions as a nutrient and vitamin for supporting the growth and protection
      of living cells under stress. Recently, the role of PQQ has also been shown as a
      bio-control agent for plant fungal pathogens, an inducer for proteins kinases
      involved in cellular differentiation of mammalian cells and as a redox sensor
      leading to development of biosensor. Recent reviews published on PQQ and enzymes
      requiring this cofactor have brought forth the case specific roles of PQQ. This
      review covers the comprehensive information on various aspects of PQQ known till
      date. These include the roles of PQQ in the regulation of cellular growth and
      differentiation in mammalian system, as a nutrient and vitamin in stress
      tolerance, in crop productivity through increasing the availability of insoluble
      phosphate and as a bio-control agent, and as a redox agent leading to the
      biosensor development. Most recent findings correlating the exceptionally high
      redox recycling ability of PQQ to its potential as anti-neurodegenerative,
      anticancer and pharmacological agents, and as a signalling molecule have been
      distinctly brought out. This review discusses different findings suggesting the
      versatility in PQQ functions and provides the most plausible intellectual basis
      to the ubiquitous roles of this compound in a large number of biological
      processes, as a nutrient and a perspective vitamin.

PMID- 22581338
TI  - Invertebrate lysozymes: diversity and distribution, molecular mechanism and in
      vivo function.

PMID- 22581339
TI  - Mammary gland stem cells: more puzzles than explanations.
AB  - Mammary gland stem cells (MaSC) have not been identified in spite of extensive
      research spanning over several decades. This has been primarily due to the
      complexity of mammary gland structure and its development, cell heterogeneity in
      the mammary gland and the insufficient knowledge about MaSC markers. At present,
      Lin (-) CD29 (i) CD49f (i) CD24 (+/mod) Sca- 1 (-) cells of the mammary  gland
      have been reported to be enriched with MaSCs. We suggest that the inclusion of
      stem cell markers like Oct4, Sox2,  Nanog and the mammary gland differentiation
      marker BRCA-1 may further narrow down the search for MaSCs. In addition, we have
      discussed some of the other unresolved puzzles on the mammary gland stem cells,
      such as their similarities and/or differences with mammary cancer stem cells, use
      of milk as source of mammary stem cells and the possibility of in vitro
      differentiation of embryonic stem (ES) cells into functional mammary gland
      structures in this review. Nevertheless, it is the lack of identity for a MaSC
      that is curtailing the advances in some of the above and other related areas.

PMID- 22581341
TI  - Hood colonoscopy in trainees: a useful adjunct to improve the performance.
AB  - BACKGROUND: The use of a transparent hood to improve colonoscopic performance has
      recently been proposed. AIMS: The purpose of this study was to evaluate whether
      using the hood might improve the cecal intubation rate, cecal intubation time,
      number of attempts needed to intubate the ileo-cecal valve, and polyp detection
      rate in trainees. METHODS: Patients undergoing colonoscopy (n = 378) were
      randomized in two groups, one studied with hood colonoscopy (n = 179) and the
      other (n = 199) with standard examination. RESULTS: No differences were found
      between hood and standard colonoscopy with respect to cecal intubation rate (95
      vs 92 %), whereas hood colonoscopy significantly shortened the cecal intubation
      time, the number of attempts needed to intubate the ileo-cecal valve, and the
      overall polyp detection rate (p < 0.01 for all these variables). CONCLUSIONS:
      Hood colonoscopy might represent a useful adjunct to standard colonoscopy,
      especially improving the performance of endoscopic trainees.

PMID- 22581342
TI  - Effects of Helicobacter pylori gamma-glutamyltranspeptidase on apoptosis and
      inflammation in human biliary cells.
AB  - BACKGROUND: Several studies have reported the presence of H. pylori in
      individuals with hepatobiliary diseases, but in vitro and in vivo studies are
      still needed. Here, we determined the effects of H. pylori gamma
      glutamyltranspeptidase (GGT) on the induction of apoptosis and IL-8 production in
      a human cholangiocarcinoma cell line (KKU-100 cells). METHODS: Cell viability and
      DNA synthesis were examined by MTT and BrdU assays, respectively. RT-PCR and
      western blot analysis were performed to assess gene and protein expression,
      respectively. IL-8 secretion in KKU-100 cells was measured by ELISA. RESULTS:
      Exposure to the H. pylori ggt (+) strain decreased KKU-100 cell survival and DNA
      synthesis when compared with cells exposed to the H. pylori ggt mutant strain.
      Treatment with recombinant H. pylori GGT (rHP-GGT) dramatically decreased cell
      survival and DNA synthesis, and stimulated apoptosis; these features corresponded
      to an increased level of iNOS gene expression in KKU-100 cells treated with rHP
      GGT. RT-PCR and western blot analyses revealed that rHP-GGT treatment enhanced
      the expression of pro-apoptotic molecules (Bax, Caspase-9, and Caspase-3) and
      down-regulated the expression of anti-apoptotic molecules (Bcl-2 and Bcl-xL). The
      extrinsic-mediated apoptosis molecules, including Fas and activated Caspase-8,
      were not expressed after treatment with rHP-GGT. Furthermore, rHP-GGT
      significantly stimulated IL-8 secretion in KKU-100 cells. CONCLUSION: Our data
      indicate that H. pylori GGT might be involved in the development of cancer in
      hepatobiliary cells by altering cell kinetics and promoting inflammation.

PMID- 22581340
TI  - Behavioural reproductive isolation and speciation in Drosophila.
AB  - The origin of premating reproductive isolation continues to help elucidate the
      process of speciation and is the central event in the evolution of biological
      species. Therefore, during the process of species formation the diverging
      populations must acquire some means of reproductive isolation so that the genes
      from one gene pool are prevented from dispersing freely into a foreign gene pool.
      In the genus Drosophila, the phenomenon of behavioural reproductive isolation,
      which is an important type of premating (prezygotic) reproductive isolating
      mechanisms, has been extensively studied and interesting data have been
      documented. In many cases incomplete sexual isolation has been observed and the
      pattern and degree of isolation within and between the species have often been
      used to elucidate the phylogenetic relationships. The present review documents an
      overview of speciation mediated through behavioural incompatibility in different
      species groups of Drosophila with particular reference to the models proposed on
      the basis of one-sided ethological isolation to predict the direction of
      evolution. This study is crucial for understanding the mechanism of speciation
      through behavioural incompatibility and also for an understanding of speciation
      genetics in future prospects.

PMID- 22581343
TI  - Detection of microcalcification clusters using Hessian matrix and foveal
      segmentation method on multiscale analysis in digital mammograms.
AB  - Mammography is the most efficient technique for detecting and diagnosing breast
      cancer. Clusters of microcalcifications have been mainly targeted as a reliable
      early sign of breast cancer and their earliest detection is essential to reduce
      the probability of mortality rate. Since the size of microcalcifications is very
      tiny and may be overlooked by the observing radiologist, we have developed a
      Computer Aided Diagnosis system for automatic and accurate cluster detection. A
      three-phased novel approach is presented in this paper. Firstly, regions of
      interest that corresponds to microcalcifications are identified. This can be
      achieved by analyzing the bandpass coefficients of the mammogram image. The
      suspicious regions are passed to the second phase, in which the nodular
      structured microcalcifications are detected based on eigenvalues of second order
      partial derivatives of the image and microcalcification pixels are segmented out
      by exploiting the foveal segmentation in multiscale analysis. Finally, by
      combining the responses coming out from the second order partial derivatives and
      the foveal method, potential microcalcifications are detected. The detection
      performance of the proposed method has been evaluated by using 370 mammograms.
      The detection method has a TP ratio of 97.76 % with 0.68 false positives per
      image. We have examined the performance of our computerized scheme using free
      response operating characteristics curve.

PMID- 22581344
TI  - Neospora caninum infection dynamics in dairy cattle.
AB  - Neospora caninum is considered in many countries as one of the key abortion
      agents in cattle. This study aims to investigate the parasite behavior in dairy
      cattle in the municipality of Avare, SP, Brazil, where abortions frequently
      occur. An ELISA was performed to compare two samplings on a total of 615 animals;
      tests were performed in the same herds with a gap of 3 years. An increase in the
      percentage of reactive animals was observed, ranging from 21.6% at the first
      sampling to 38.9% at the second sampling. Of the 176 animals tested at both
      samplings, 61.93% retained a non-reactive status, 15.9% retained a reactive
      status, 19.88% switched from non-reactive to reactive and 2.27% switched from
      reactive to non-reactive. Of the 100 animals with reproductive disturbances, 50%
      presented anti-Neospora antibodies, thereby indicating the presence of the
      protozoa. When comparing cows and their respective female offspring, a
      predominance of horizontal infection was observed. Moreover, considering the
      significant percentage of animals that switched from non-reactive to reactive and
      the abundant presence of dogs among the herds, the N. caninum transmission may be
      attributed to presence of carnivores.

PMID- 22581345
TI  - How photoperiods affect the immature development of forensically important
      blowfly species Chrysomya albiceps (Calliphoridae).
AB  - The purpose of this study was to verify the influence of different photoperiods
      on larval body weight, post-embryonic development, and viability of Chrysomya
      albiceps. The bioassays were performed in acclimatized chamber at 27 +/- 1 
      degrees C and 60 +/- 10 % relative humidity regulated by three different light
      and dark cycles for a period of 24 h-12:12, 24:00, and 00:24. Four replications
      with 50 newly hatched larvae each were used per photoperiod. The larvae were
      placed in container containing bovine ground meat (50 g). When mature larvae
      spontaneously abandoned the diet, they were individually weighed and separated
      into glass tubes until emergence. The larvae that did not abandon the diet were
      not weighed. The larvae from 24 h of photophase did not abandon the diet and
      pupated inside, so these larvae were not weighed and the larval and pupal
      developments were not registered. The mean of larval body weight did not vary
      between the 24 h scotophase and 12 h photophase. The mean duration of larval
      developmental time varied significantly when comparing the 24 h scotophase and
      the 12 h photophase, and the pupal developmental time also varied for the same
      photoperiods; in both stages, the duration of development was faster in the 24 h
      scotophase. The developmental time of neo-larvae to adult was verified in all
      photoperiods and gradually increased as photophase increased. There was a trend
      to augment of viability with the reduction of photophase length.

PMID- 22581346
TI  - Phylogenetic relationships in Demodex mites (Acari: Demodicidae) based on
      mitochondrial 16S rDNA partial sequences.
AB  - To confirm phylogenetic relationships in Demodex mites based on mitochondrial 16S
      rDNA partial sequences, mtDNA 16S partial sequences of ten isolates of three
      Demodex species from China were amplified, recombined, and sequenced and then
      analyzed with two Demodex folliculorum isolates from Spain. Lastly, genetic
      distance was computed, and phylogenetic tree was reconstructed. MEGA 4.0 analysis
      showed high sequence identity among 16S rDNA partial sequences of three Demodex
      species, which were 95.85 % in D. folliculorum, 98.53 % in Demodex canis, and
      99.71 % in Demodex brevis. The divergence, genetic distance, and
      transition/transversions of the three Demodex species reached interspecies level,
      whereas there was no significant difference of the divergence (1.1 %), genetic
      distance (0.011), and transition/transversions (3/1) of the two geographic D.
      folliculorum isolates (Spain and China). Phylogenetic trees reveal that the three
      Demodex species formed three separate branches of one clade, where D.
      folliculorum and D. canis gathered first, and then gathered with D. brevis. The
      two Spain and five China D. folliculorum isolates did not form sister clades. In
      conclusion, 16S mtDNA are suitable for phylogenetic relationship analysis in low
      taxa (genus or species), but not for intraspecies determination of Demodex. The
      differentiation among the three Demodex species has reached interspecies level.

PMID- 22581347
TI  - Golimumab for the treatment of refractory juvenile idiopathic arthritis
      associated uveitis.

PMID- 22581348
TI  - Autocrine effect of EGFR ligands on the pro-inflammatory response induced by
      PM(2.5) exposure in human bronchial epithelial cells.
AB  - Human exposure to PM(2.5) (particulate matter with an aerodynamic diameter below
      2.5 MUm) is known to be responsible for airway inflammation and may also induce
      airway remodelling. In respiratory epithelial cells exposed to PM(2.5), releases
      of pro-inflammatory cytokines such as granulocyte macrophage-colony stimulating
      factor (GM-CSF) and growth factor ligands of the epidermal growth factor receptor
      (EGFR) are increased. The present study aimed at determining the involvement of
      EGFR ligands by autocrine effects in PM(2.5)-induced GM-CSF release. PM(2.5)
      exposure triggers GM-CSF release by human bronchial epithelial (HBE) cells. This
      release is dependent on EGFR activation by ligand binding as it is inhibited by
      AG1478, an inhibitor of EGFR tyrosine kinase activity as well as by a
      neutralizing anti-EGFR antibody. The use of conditioned medium from cells
      previously exposed to PM(2.5) demonstrates that PM(2.5)-exposed cells release
      soluble EGFR ligands able to induce GM-CSF release by an autocrine manner. It was
      further demonstrated by inhibiting tumour-necrosis factor-alpha converting enzyme
      (TACE) that is involved in some EGFR ligand shedding. TAPI-2 and GM-6001, two
      TACE inhibitors, prevented the PM(2.5)-induced GM-CSF release as well as the
      silencing of TACE by siRNA. We provide evidence that the pro-inflammatory
      response induced by PM(2.5) exposure on HBE cells, results from an autocrine
      effect of EGFR ligands released by TACE activity. This autocrine loop by
      eliciting and sustaining inflammation could contribute to exacerbation of airway
      remodelling in respiratory-compromised individuals.

PMID- 22581349
TI  - Regioselective synthesis of pyrimido[1,2-a][1,3,5]triazin-6-ones via reaction of
      1-(6-oxo-1,6-dihydropyrimidin-2-yl)guanidines with triethylorthoacetate:
      observation of an unexpected rearrangement.
AB  - A novel thermal rearrangement, involving pyrimidine ring opening and subsequent
      ring closure leading to recyclization of the system, was identified in the
      reaction of (6-oxo-1,6-dihydropyrimidin-2-yl)guanidines 3 (where NR(1)R(2) =
      NH(2), NH alkyl, NH aralkyl, NHCH(2)Ph(R)) with triethyl orthoacetate, affording
      4-substituted-2-methyl-6H-pyrimido[1,2-a][1,3,5]triazin-6-ones 6 and their ring
      opened products. However, no such rearrangement was observed with (6-oxo-1,6
      dihydropyrimidin-2-yl)guanidines 3 bearing a tertiary amino or anilino
      substituent (i.e. where NR(1)R(2) = N(CH(3))(2), indoline, morpholino, NHAr). As
      expected, 2-substituted-4-methyl-6H-pyrimido[1,2-a][1,3,5]triazin-6-ones 4 were
      obtained as the final products. Experimental structural determination and
      theoretical studies were carried out to get an understanding of the observed
      thermal rearrangement. In addition, an attempt to obtain similar pyrimido[1,2
      a][1,3,5]triazin-6-ones using N,N-dimethylacetamide dimethyl acetal (DMA-DMA) as
      one carbon inserting synthon had furnished triazine ring annulated product 14
      bearing N,N-dimethyl enamino substituent at position 4 as a result of further
      reaction with a second molecule of DMA-DMA.

PMID- 22581350
TI  - Bridging knee arthrodesis for limb salvage using an intramedullary cemented nail:
      a retrospective outcome analysis of a case series.
AB  - INTRODUCTION: Failed total knee replacement with compromised bone and soft
      tissues can be challenging. In these situations, arthrodesis remains a treatment
      option of a limb-saving procedure. METHODS: We investigated the outcome of
      treatment with an intramedullary cemented knee arthrodesis nail implanted in 22
      consecutive patients with forlorn situations after failed total knee replacement.
      RESULTS: There were three major complications due to re-infection and two minor
      complications due to wound-healing disturbances that healed with the implant
      retained after an average follow-up of 3.4 years. Clinical examination, Short
      Form-36 and Oxford knee scores revealed low pain levels, safe implant anchorage,
      and improved stability of the knee, whilst autonomous mobility utilizing walking
      aids was still possible. CONCLUSION: Bridging knee arthrodesis with an
      intramedullary nail is a valuable salvage procedure with acceptable clinical
      results. As recurring infection remains the most challenging complication,
      regular clinical and radiological follow-up examinations are necessary following
      implant-related knee arthrodesis to allow timely intervention in case of
      loosening.

PMID- 22581351
TI  - A new method to measure ligament balancing in total knee arthroplasty: laxity
      measurements in 100 knees.
AB  - BACKGROUND: Ligament balancing is considered a prerequisite for good function and
      survival in total knee arthroplasty (TKA). However, there is no consensus on how
      to measure ligament balance intra-operatively and the degree of stability
      obtained after different balancing techniques is not clarified. PURPOSE: This
      study presents a new method to measure ligament balancing in TKA and reports on
      the results of a try-out of this method and its inter-observer reliability.
      METHODS: After the implantation of the prosthesis, spatulas of different
      thickness were used to measure medial and lateral condylar lift-off in flexion
      and extension in 70 ligament-balanced knees and in 30 knees were ligament
      balancing was considered unnecessary. Inter-observer reliability for the new
      method was estimated and the degree of medial-lateral symmetry in extension and
      in flexion, and the equality of the extension gaps and flexion gaps were
      calculated. RESULTS: The method was feasible in all operated knees, and found to
      be very reliable (intraclass correlation coefficient = 0.88). We found no
      statistically significant difference in condylar lift-off between the ligament
      balanced and the non ligament-balanced group, however, there was a tendency to
      more outliers in flexion in the ligament-balanced group. CONCLUSIONS: Our method
      for measuring ligament balance is reliable and provides valuable information in
      assessing laxity intra-operatively. This method may be a useful tool in further
      research on the relationship between ligament balance, function and survival of
      TKA.

PMID- 22581352
TI  - Utility of tibial tubercle osteotomy in the setting of periprosthetic infection
      after total knee arthroplasty.
AB  - PURPOSE: This study reports radiographic and clinical treatment outcomes of
      tibial tubercle osteotomy (TTO) used for two-stage revision total knee
      arthroplasty (TKA) in the setting of periprosthetic infection. METHODS: Thirty
      six patients with 51 TTOs used for infected TKA were retrospectively analysed
      from 2000 to 2010. In 15 of 36 patients, TTO was used in a sequential manner
      during both first and second stage procedures. The mean follow-up period was 57
      months (range seven-126 months). RESULTS: The mean pre-operative range of knee
      motion was 40 degrees  (range 10-90 degrees ), and at latest follow-up it was 92
      degrees  (range 50-140 degrees ). The Knee Society knee scores and function
      scores were 47 and 9 pre-operatively and 82 and 72 at latest follow-up,
      respectively. Bony union was achieved in all cases except one nonunion of an
      avulsion fragment of the osteotomy segment without functional deterioration.
      CONCLUSIONS: TTO can be a useful extensile surgical approach for treatment of
      infected TKA with satisfactory clinical and radiographic outcomes.

PMID- 22581353
TI  - Long bone reconstruction using multilevel lengthening of bone defect fragments.
AB  - PURPOSE: This paper presents experimental findings to substantiate the use of
      multilevel bone fragment lengthening for managing extensive long bone defects
      caused by diverse aetiologies and shows its clinical introduction which could
      provide a solution for the problem of reducing the total treatment time. METHODS:
      Both experimental and clinical multilevel lengthening to bridge bone defect gaps
      was performed with the use of the Ilizarov method only. RESULTS: The experimental
      findings and clinical outcomes showed that multilevel defect fragment lengthening
      could provide sufficient bone formation and reduction of the total osteosynthesis
      time in one stage as compared to traditional Ilizarov bone transport. The method
      of multilevel regeneration enabled management of critical-size defects that
      measured on average 13.5 +/- 0.7 cm in 78 patients. CONCLUSIONS: The experimental
      and clinical results proved the efficiency of the Ilizarov non-free multilevel
      bone plasty that can be recommended for practical use.

PMID- 22581354
TI  - RANKL, denosumab, and giant cell tumor of bone.
AB  - PURPOSE OF REVIEW: Giant cell tumor (GCT) of bone is a benign, osteolytic
      neoplasm of bone. The receptor activator of NF-KB ligand (RANKL) pathway has
      recently been shown to play a key role in the pathogenesis of GCT. RECENT
      FINDINGS: Treatment for refractory, recurrent, or metastatic GCT remains
      challenging. The recent development of a monoclonal antibody to RANKL, denosumab,
      offers promise in the management of these patients. A recent phase 2 study
      suggested denosumab offers disease and symptom control for patients with advanced
      or refractory disease. In this population, denosumab appears to be well
      tolerated. There are key questions which remain to be addressed, including
      patient selection, optimal scheduling, use as an adjuvant, and application to
      other giant cell-rich disorders. SUMMARY: Denosumab offers a new treatment option
      for a subset of patients with previously untreatable GCT. The role of denosumab
      in curative treatment is the subject of ongoing studies.

PMID- 22581355
TI  - Anal margin cancer:  current situation and ongoing trials.
AB  - PURPOSE OF REVIEW: To summarize the current treatment approach in managing anal
      margin cancer and to discuss potential emerging new strategies. RECENT FINDINGS:
      The management of anal margin cancer has been evolving over the past three
      decades. The treatment paradigm has been shifted from radical surgical resection
      to an organ-preservation approach. Multimodality strategies incorporating
      radiation or even chemoradiation are frequently considered in some cases.
      However, because of the rarity of the disease, the disease frequently remains an
      overlooked topic. At present, there is no prospective trial addressing the best
      clinical management of the disease. SUMMARY: The clinical course of squamous cell
      carcinoma of the anal margin is very different from that of the anal canal. The
      biology of anal margin cancer has not been actively explored and fully
      understood. There is a need to formulate a consensus approach for the clinical
      management of the disease. In addition, incorporation of new therapeutics in this
      disease especially in those with advanced stages should be explored.

PMID- 22581356
TI  - Robotic surgery in gynecologic oncology.
AB  - PURPOSE OF REVIEW: The objective of this article is to review the recently
      published literature on the use of robotic surgery in the management of
      gynecologic malignancies. RECENT FINDINGS: Retrospective data collected from many
      institutions support the use of robotic surgery in the management of cervical,
      endometrial, and early-stage ovarian cancer. Benefits to robotic surgery include
      decreased blood loss, fewer perioperative complications, and decreased length of
      hospital stay, especially when compared to an open cohort. Disadvantages include
      costs associated with the robotic system and disposable equipment, accessibility
      to robotic surgical systems, loss of haptic sensation with the device, and lack
      of prospective trials validating its use in gynecologic oncology. SUMMARY:
      Current evidence establishes a role for the use of robotic surgery in the
      treatment of gynecologic malignancies. Further research should be implemented to
      validate the use of robotic surgery in gynecologic malignancies and to compare
      its outcomes to those of open and laparoscopic surgery.

PMID- 22581357
TI  - Molecular targets and targeted therapeutics in endometrial cancer.
AB  - PURPOSE OF REVIEW: Endometrial cancer is the most common gynaecological
      malignancy in the western world. Two clinicopathological subtypes are recognized:
      type I (endometrioid) and type II (nonendometrioid) carcinomas. This review
      describes the molecular alterations in endometrial cancer and how this knowledge
      is leading to the development of novel treatments in this area. RECENT FINDINGS:
      Molecularly targeted agents have entered clinical trials in endometrial cancer.
      So far, mechanistic target of rapamycin (mTOR) inhibitors and antiangiogenic
      agents appear promising and are being pursued further in addition to other
      targeted approaches. SUMMARY: The clinicopathological and molecular heterogeneity
      of endometrial cancer needs to be taken into account in the design of future
      clinical trials as well as the incorporation of robust biomarkers for the success
      of therapeutic strategies in endometrial cancer.

PMID- 22581358
TI  - Chemotherapy during pregnancy.
AB  - PURPOSE OF REVIEW: Cancer during pregnancy is uncommon, although not rare. As
      women in developed societies defer childbearing and the incidence of most
      malignancies rises with increasing age, the situation in which cancer complicates
      pregnancy is expected to become more common. Cancer staging and treatment can be
      performed during pregnancy and should be defined in a multidisciplinary setting.
      Here, we describe the potential to use chemotherapy during pregnancy. RECENT
      FINDINGS: New insights add to the practice of administering chemotherapy from 14
      weeks gestational age onwards. The placental barrier function protects the fetus.
      The physiologic gestational changes reduce the maternal serum levels of
      chemotherapy, although the pharmacodynamic impact remains unknown. Comedication
      to chemotherapy can be administered on strict indications. Chemotherapy after 35
      weeks is not recommended as an interval of at least 3 weeks is preferred between
      chemotherapy administration and delivery. Recent data show that the long-term
      outcome of children antenatally exposed to chemotherapy is comparable to children
      of the same age. Nevertheless, a higher rate of neurodevelopmental problems was
      encountered after preterm birth, also in this selected patient population.
      SUMMARY: Administration of chemotherapy during pregnancy may decrease the need
      for early delivery, and thus prematurity.

PMID- 22581359
TI  - Osteoporosis and bone health in HIV.
AB  - Patients with HIV can develop several complications that involve bone including
      low bone mineral density and osteoporosis, osteonecrosis, and rarely
      osteomalacia. Low bone mineral density leading to osteoporosis is the most common
      bone pathology. This may result from HIV infection (directly or indirectly),
      antiretroviral toxicity, or as a consequence of other co-morbidities. The
      clinical relevance of osteoporosis in HIV infection has been uncertain; however,
      fragility fractures are increasingly reported in HIV-infected patients. Further
      research is required to understand the pathogenesis of osteoporosis in HIV
      infected patients and determine effective management; however, initiation of
      antiretroviral therapy seems to accelerate (in the short-term) bone
      demineralization. Tenofovir may be associated with a greater degree of short-term
      loss of bone density than other antiviral agents and the potential long-term bone
      dysfunction is unclear. As the HIV-infected population ages, screening for low
      bone mineral density will become increasingly important.

PMID- 22581360
TI  - Treatment of latent tuberculosis infection in HIV: shorter or longer?
AB  - Nine months of daily isoniazid is efficacious in treating latent M. tuberculosis
      infection, but completion rates are low, limiting treatment effectiveness. In
      2011, three important studies were published involving novel regimens for the
      treatment of latent M. tuberculosis infection. At least 36 months of isoniazid
      was more effective than 6 months of isoniazid in one study, but not in another
      both of which were conducted among tuberculin skin test positive HIV-infected
      adults living in high tuberculosis incidence settings. Three months of once
      weekly isoniazid plus rifapentine or twice-weekly isoniazid plus rifampin (both
      given under direct observation) resulted in tuberculosis rates similar to those
      seen with 6 months of isoniazid among HIV-infected persons in high tuberculosis
      incidence settings. Three months of once-weekly, directly-observed isoniazid plus
      rifapentine was at least as effective as 9 months of daily isoniazid among
      predominantly HIV-uninfected persons living in low and medium tuberculosis
      incidence countries. The 3-month once-weekly isoniazid plus rifapentine regimen
      demonstrates promise for treatment of latent M. tuberculosis infection in HIV
      infected persons.

PMID- 22581361
TI  - Picroside II protects cardiomyocytes from hypoxia/reoxygenation-induced apoptosis
      by activating the PI3K/Akt and CREB pathways.
AB  - Picroside II, an iridoid glucoside found in the root of Picrorhiza
      scrophulariiflora Pennell (Scrophulariaceae), has been demonstrated to reduce
      apoptosis in neuronal cells and other cell types. However, whether picroside II
      has a protective effect against cardiomyocyte apoptosis is poorly understood. In
      the present study, we investigated the cardioprotective role of picroside II and
      the underlying mechanisms in hypoxia/reoxygenation-induced cardiomyocyte
      apoptosis. The pretreatment with picroside II markedly attenuated
      hypoxia/reoxygenation-induced cell damage dose-dependently, which was evident by
      the increased cell viability and the corresponding decrease in lactate
      dehydrogenase release (LDH). The pretreatment with picroside II inhibited
      apoptosis confirmed by Annexin V-FITC staining, Hoechst 33258 nuclear staining
      and by assessment of caspase-3 activity. In addition, we found that picroside II
      not only increased the expression of Bcl-2, while decreasing Bax expression, but
      also augmented Akt and cAMP response element-binding protein (CREB)
      phosphorylation and ultimately inhibited hypoxia/reoxygenation-induced apoptosis.
      Furthermore, the protective effects of picroside II were abrogated by
      pretreatment of the cells with wortmannin or LY294002, a specific PI3K inhibitor.
      The present study suggests that picroside II inhibits hypoxia/reoxygenation
      induced apoptosis in cardiomyocytes by activating the PI3K/Akt and CREB pathways
      and modulating expression of Bcl-2 and Bax.

PMID- 22581362
TI  - Bacteremia with Streptococcus pneumoniae: sepsis and other risk factors for 30
      day mortality--a hospital-based cohort study.
AB  - We conducted a hospital-based cohort study among adult patients with first-time
      Streptococcus pneumoniae bacteremia (SPB) from 2000 through 2008. Patients were
      identified in a population-based bacteremia database and followed up for
      mortality through the Danish Civil Registration System (CRS). The aim of the
      study was to determine the focal diagnosis of SPB, the severity of sepsis at
      presentation, demographics and comorbidity characteristics of the patients, and
      to determine the 30-day mortality rate and factors related to mortality. We
      identified 481 patients, of which 238 were males. The mean age of the patients
      was 65 years. The focal diagnosis of the SPB was pneumonia in 381 (79 %)
      patients, followed in frequency by meningitis in 33 (7 %) patients. Of the 481
      patients, 390 (81 %) had community-acquired SPB. Of these, 23 (6 %) did not have
      sepsis, 132 (34 %) had sepsis, 224 (57 %) had severe sepsis, and 11 (3 %) were in
      septic shock. Overall, the 30-day mortality was 16 %. Mortality increased with
      the severity of sepsis. There was no association between the focal diagnosis of
      SPB or the number of diagnoses and mortality. Nosocomial infection, male sex,
      increasing age, and increasing comorbidity were all associated with an increased
      30-day mortality rate.

PMID- 22581363
TI  - Poly(ADP-ribose) polymerase-2: emerging transcriptional roles of a DNA-repair
      protein.
AB  - Poly(ADP-ribose) polymerase (PARP)-2 is a nuclear enzyme that belongs to the PARP
      family and PARP-2 is responsible for 5-15 % of total cellular PARP activity. PARP
      2 was originally described in connection to DNA repair and in physiological and
      pathophysiological processes associated with genome maintenance (e.g., centromere
      and telomere protection, spermiogenesis, thymopoiesis, azoospermia, and
      tumorigenesis). Recent reports have identified important rearrangements in gene
      expression upon the knockout of PARP-2. Such rearrangements heavily impact
      inflammation and metabolism. Metabolic effects are mediated through modifying
      PPARgamma and SIRT1 function. Altered gene expression gives rise to a complex
      phenotype characterized primarily by enhanced mitochondrial activity that results
      both in beneficial (loss of fat, enhanced insulin sensitivity) and in
      disadvantageous (pancreatic beta cell hypofunction upon high fat feeding)
      consequences. Enhanced mitochondrial biogenesis provides protection in oxidative
      stress-related diseases. Hereby, we review the recent developments in PARP-2
      research with special attention to the involvement of PARP-2 in transcriptional
      and metabolic regulation.

PMID- 22581364
TI  - NOX enzymes: potential target for the treatment of acute lung injury.
AB  - Acute lung injury (ALI) and its more severe form, acute respiratory distress
      syndrome (ARDS), is characterized by acute inflammation, disruption of the
      alveolar-capillary barrier, and in the organizing stage  by alveolar pneumocytes
      hyperplasia and extensive lung fibrosis. The cellular and molecular mechanisms
      leading to the development of ALI/ARDS are not completely understood, but there
      is evidence that reactive oxygen species (ROS) generated by inflammatory cells as
      well as epithelial and endothelial cells are responsible for inflammatory
      response, lung damage, and abnormal repair. Among all ROS-producing enzymes, the
      members of NADPH oxidases (NOXs), which are widely expressed in different lung
      cell types, have been shown to participate in cellular processes involved in the
      maintenance of lung integrity. It is not surprising that change in NOXs'
      expression and function is involved in the development of ALI/ARDS. In this
      context, the use of NOX inhibitors could be a possible therapeutic perspective in
      the management of this syndrome. In this article, we summarize the current
      knowledge concerning some cellular aspects of NOXs localization and function in
      the lungs, consider their contribution in the development of ALI/ARDS and discuss
      the place of NOX inhibitors as potential therapeutical target.

PMID- 22581366
TI  - Targeting NADPH oxidases for the treatment of cancer and inflammation.
AB  - NADPH oxidases are a family of oxidases that utilize molecular oxygen to generate
      hydrogen peroxide and superoxide, thus indicating physiological functions of
      these highly reactive and short-lived species. The regulation of these NADPH
      oxidases (nox) enzymes is complex, with many members of this family exhibiting
      complexity in terms of subunit composition, cellular location, and tissue
      specific expression. While the complexity of the nox family (Nox1-5, Duox1, 2) is
      daunting, the complexity also allows for targeting of NADPH oxidases in disease
      states. In this review, we discuss which inflammatory and malignant disorders can
      be targeted by nox inhibitors, as well as clinical experience in the use of such
      inhibitors.

PMID- 22581365
TI  - Targeting microglia-mediated neurotoxicity: the potential of NOX2 inhibitors.
AB  - Microglia are key sentinels of central nervous system health, and their
      dysfunction has been widely implicated in the progressive nature of
      neurodegenerative diseases. While microglia can produce a host of factors that
      are toxic to neighboring neurons, NOX2 has been implicated as a common and
      essential mechanism of microglia-mediated neurotoxicity. Accumulating evidence
      indicates that activation of the NOX2 enzyme complex in microglia is neurotoxic,
      both through the production of extracellular reactive oxygen species that damage
      neighboring neurons as well as the initiation of redox signaling in microglia
      that amplifies the pro-inflammatory response. More specifically, evidence
      supports that NOX2 redox signaling enhances microglial sensitivity to pro
      inflammatory stimuli, and amplifies the production of neurotoxic cytokines, to
      promote chronic and neurotoxic microglial activation. Here, we describe the
      evidence denoting the role of NOX2 in microglia-mediated neurotoxicity with an
      emphasis on Alzheimer's and Parkinson's disease, describe available inhibitors
      that have been tested, and detail evidence of the neuroprotective and therapeutic
      potential of targeting this enzyme complex to regulate microglia.

PMID- 22581367
TI  - Molecular insights into the regulation of iron metabolism during the prenatal and
      early postnatal periods.
AB  - Molecular iron metabolism and its regulation are least well understood in the
      fetal and early postnatal periods of mammalian ontogenic development. The scope
      of this review is to summarize recent progress in uncovering the molecular
      mechanisms of fetal iron homeostasis, introduce the molecules involved in iron
      transfer across the placenta, and briefly explain the role of iron transporters
      in the absorption of this microelement during early postnatal life. These issues
      are discussed and parallels are drawn with the relatively well-established system
      for elemental and heme iron regulation in adult mammals. We conclude that
      detailed investigations into the regulatory mechanisms of iron metabolism at
      early stages of development are required in order to optimize strategies to
      prevent neonatal iron deficiency. We propose that newborn piglets represent a
      suitable animal model for studies on iron deficiency anemia in neonates.

PMID- 22581369
TI  - Transcriptional silencing of the inhibin-alpha gene in human gastric carcinoma
      cells.
AB  - Although inhibin was first identified as a hormone regulating pituitary FSH
      secretion, it was later recognized to act as a tumor suppressor in the gonad and
      adrenal glands. Recently, the alpha subunit of this dimeric hormone (inhibin
      alpha) was reported to be involved in prostate tumorigenesis. To identify
      additional roles outside the reproductive axis, we investigated inhibin-alpha
      gene activity and subsequent cell fate in human gastric cancer cells. The results
      were as follows: all the gastric cancer cells had at least one of a set of
      abnormalities including hypermethylation of the promoter, mutation of the 5'-UTR
      or allelic imbalance including LOH in the inhibin-alpha gene. Hypermethylation of
      the promoter and mutation of the 5'-UTR in inhibin-alpha were observed in SNU-1,
      SNU-5 and SNU-484 cells. LOH was observed in AGS, KATO III, SNU-5, SNU-484 and
      SNU-668 cells. Treatment with 5-AzaC, a demethylating agent, induced
      demethylation of the inhibin-alpha promoter in the SNU-1, SNU-5 and SNU-484 cell
      lines, with the CpG5 site being strongly influenced by 5-AzaC. In addition,
      inhibin-alpha mRNA and protein were maintained at low levels in most of the
      gastric cancer cell lines. These low levels of mRNA and protein expression could
      be increased in most lines by treatment with 5-AzaC. These increased inhibin
      alpha expression levels seemed to be closely associated with apoptosis and
      suppression of cell growth. Taken together, our results reveal that the inhibin
      alpha gene is transcriptionally silenced in human gastric cancer cells, and that
      reactivation of the gene suppresses their growth characteristics. This suggests
      that inhibin-alpha may have a more general tumor suppressor activity outside the
      reproductive axis.

PMID- 22581368
TI  - Are Rab proteins the link between Golgi organization and membrane trafficking?
AB  - The fundamental separation of Golgi function between subcompartments termed
      cisternae is conserved across all eukaryotes. Likewise, Rab proteins, small
      GTPases of the Ras superfamily, are putative common coordinators of Golgi
      organization and protein transport. However, despite sequence conservation, e.g.,
      Rab6 and Ypt6 are conserved proteins between humans and yeast, the fundamental
      organization of the organelle can vary profoundly. In the yeast Saccharomyces
      cerevisiae, the Golgi cisternae are physically separated from one another, while
      in mammalian cells, the cisternae are stacked one upon the other. Moreover, in
      mammalian cells, many Golgi stacks are typically linked together to generate a
      ribbon structure. Do evolutionarily conserved Rab proteins regulate secretory
      membrane trafficking and diverse Golgi organization in a common manner? In
      mammalian cells, some Golgi-associated Rab proteins function in coordination of
      protein transport and maintenance of Golgi organization. These include Rab6,
      Rab33B, Rab1, Rab2, Rab18, and Rab43. In yeast, these include Ypt1, Ypt32, and
      Ypt6. Here, based on evidence from both yeast and mammalian cells, we speculate
      on the essential role of Rab proteins in Golgi organization and protein
      transport.

PMID- 22581370
TI  - Rational design of true monomeric and bright photoactivatable fluorescent
      proteins.
AB  - Monomeric (m)Eos2 is an engineered photoactivatable fluorescent protein widely
      used for super-resolution microscopy. We show that mEos2 forms oligomers at high
      concentrations and forms aggregates when labeling membrane proteins, limiting its
      application as a fusion partner. We solved the crystal structure of tetrameric
      mEos2 and rationally designed improved versions, mEos3.1 and mEos3.2, that are
      truly monomeric, are brighter, mature faster and exhibit higher photon budget and
      label density.

PMID- 22581371
TI  - M-Track: detecting short-lived protein-protein interactions in vivo.
AB  - We developed a protein-proximity assay in yeast based on fusing a histone lysine
      methyltransferase onto a bait and its substrate onto a prey. Upon binding, the
      prey is stably methylated and detected by methylation-specific antibodies. We
      applied this approach to detect varying interaction affinities among proteins in
      a mitogen-activated protein kinase pathway and to detect short-lived interactions
      between protein phosphatase 2A and its substrates that have so far escaped direct
      detection.

PMID- 22581372
TI  - Resolution doubling in live, multicellular organisms via multifocal structured
      illumination microscopy.
AB  - We demonstrate three-dimensional (3D) super-resolution in live multicellular
      organisms using structured illumination microscopy (SIM). Sparse multifocal
      illumination patterns generated by a digital micromirror device (DMD) allowed us
      to physically reject out-of-focus light, enabling 3D subdiffractive imaging in
      samples eightfold thicker than had been previously imaged with SIM. We imaged
      samples at one 2D image per second, at resolutions as low as 145 nm laterally and
      400 nm axially. In addition to dual-labeled, whole fixed cells, we imaged GFP
      labeled microtubules in live transgenic zebrafish embryos at depths >45 MUm. We
      captured dynamic changes in the zebrafish lateral line primordium and observed
      interactions between myosin IIA and F-actin in cells encapsulated in collagen
      gels, obtaining two-color 4D super-resolution data sets spanning tens of time
      points and minutes without apparent phototoxicity. Our method uses commercially
      available parts and open-source software and is simpler than existing SIM
      implementations, allowing easy integration with wide-field microscopes.

PMID- 22581373
TI  - Critical thresholds for cerebrovascular reactivity: fact or fiction?

PMID- 22581374
TI  - Anger and irritability symptoms among youth with ODD: cross-informant versus
      source-exclusive syndromes.
AB  - We examined differences in co-occurring psychological symptoms and background
      characteristics among clinically referred youth with oppositional defiant
      disorder (ODD) with and without anger/irritability symptoms (AIS) according to
      either parent or teacher (source-exclusive) and both informants (cross
      informant), youth with noncompliant symptoms (NS) of ODD, and non-ODD clinic
      controls. Parents and teachers evaluated 1127 youth (ages 6-18) with a DSM-IV
      referenced rating scale to assess ODD and co-occurring psychological symptoms.
      Parents also completed a background questionnaire (demographic, developmental,
      treatment, relationship, and academic characteristics) and teachers rated school
      functioning. Source-exclusive AIS groups were associated with different clinical
      features, and there was some evidence that cross-informant youth had more mental
      health concerns than source-exclusive groups. Findings varied to some extent
      among older (12-18 years) versus younger (6-11 years) youth. In general, the NS
      group (youth without AIS) was the most similar to clinic controls. AIS and NS are
      likely candidates for component phenotypes in ODD and continued research into
      their pathogenesis may have important implications for nosology, etiology, and
      intervention.

PMID- 22581375
TI  - Parent-reported Attention Deficit/Hyperactivity symptomatology in preschool-aged
      children: factor structure, developmental change, and early risk factors.
AB  - Although Attention Deficit/Hyperactivity Disorder (ADHD) has increasingly been
      studied in preschool-aged children, relatively few studies have provided a
      comprehensive evaluation of the factor structure and patterns of developmental
      changes in parent-reported ADHD symptomatology across the early childhood period.
      This study used confirmatory factor analyses to test for longitudinal measurement
      invariance of ADHD symptoms and semi-parametric finite mixture models to identify
      prototypic patterns of developmental changes in ADHD symptomatology from 3 to 5
      years of age. Participants were 1155 children and their parents who participated
      in a prospective longitudinal study involving a representative sample of children
      who resided in six non-metropolitan counties in the United States. Results
      indicated that (1) ADHD symptomatology was best represented by a single latent
      factor that exhibited partial measurement invariance from 3 to 5 years of age,
      (2) 8.5 % of children exhibited sustained high levels of ADHD symptoms from age 3
      5 years, and (3) a variety of risk factors differentiated children with sustained
      high from those with sustained low levels of ADHD, relatively few (most notably
      caregiver education) were able to differentiate children with sustained high
      levels of ADHD symptoms from all other groups. Children who exhibit persistent
      ADHD symptomatology across the early childhood period may define a clinically
      important group for etiologic research and/or early intervention efforts.

PMID- 22581376
TI  - Evaluation of multifocal visual evoked potentials in patients with Graves'
      orbitopathy and subclinical optic nerve involvement.
AB  - Dysthyroid optic neuropathy is the most serious, although infrequent (8-10 %)
      complication in Graves' orbitopathy (GO). It is known that early stages of
      compressive optic neuropathy may produce reversible visual field defects,
      suggesting axoplasmic stasis rather than ganglion cell death. This observational,
      cross-sectional, case-control study assessed 34 consecutive patients (65 eyes)
      with Graves' hyperthyroidism and longstanding GO and 31 age-matched control
      subjects. The patients' multifocal visual evoked potentials (mfVEP) were compared
      to their clinical and psychophysical (standard automated perimetry [SAP]) and
      structural (optic coherence tomography [OCT]) diagnostic test data. Abnormal
      cluster defects were found in 12.3 % and 3.1 % of eyes on the interocular and
      monocular amplitude analysis mfVEP probability plots, respectively. As well,
      mfVEP latencies delays were found in 13.8 and 20 % of eyes on the interocular and
      monocular analysis probability plots, respectively. Interestingly, 19 % of
      patients with GO had ocular hypertension, and a strong correlation between
      intraocular pressure measured at upgaze and mfVEP latency was found. MfVEP
      amplitudes and visual acuity were significantly related to each other (P < 0.05),
      but not with the latencies delays. However, relationships between the interocular
      or monocular mfVEP amplitudes and latencies analysis and SAP indices or OCT data
      were not statistically significant. One-third of our patients with GO showed
      changes in the mfVEP, indicating significant subclinical optic nerve dysfunction.
      In this sense, the mfVEP may be a useful diagnostic tool in the clinic for early
      diagnosis and monitoring of optic nerve function abnormalities in patients with
      GO.

PMID- 22581377
TI  - Stimulus chromatic properties affect period doubling in the human cone flicker
      ERG.
AB  - Period doubling in the full-field cone flicker electroretinogram (ERG) refers to
      an alternation in waveform amplitude and/or shape from cycle to cycle, presumably
      owing to the operation of a nonlinear gain control mechanism. This study examined
      the influence of stimulus chromatic properties on the characteristics of period
      doubling in order to better understand the underlying mechanism. ERGs were
      acquired from 5 visually normal subjects in response to sinusoidally modulated
      flicker presented at frequencies from 25 to 100 Hz. The test stimuli and the pre
      stimulus adaptation were either long wavelength (R), middle wavelength (G), or an
      equal combination of long and middle wavelengths (Y), all equated for photopic
      luminance. Fourier analysis was used to obtain the response amplitude at the
      stimulus frequency F and at a harmonic frequency of 3F/2, which was used as the
      index of period doubling. The frequency-response function for 3F/2 typically
      showed two peaks, occurring at approximately 33.3 and 50 Hz. However, the
      magnitude of period doubling within these frequency regions was dependent on the
      chromatic properties of both the test stimulus and the pre-stimulus adaptation.
      Period doubling was generally smallest when an R test was used, even though the
      stimuli were luminance-equated and the amplitude of F did not differ between the
      various conditions. The pattern of results indicates that the mechanism that
      generates period doubling is influenced by chromatic signals from both the test
      stimulus and the pre-stimulus adaptation, even though the high stimulus
      frequencies presumably favor the achromatic luminance system.

PMID- 22581378
TI  - Social support during the postpartum period: mothers' views on needs,
      expectations, and mobilization of support.
AB  - Research has indicated that social support is a major buffer of postpartum
      depression. Yet little is known concerning women's perceptions on social support
      during the postpartum period. The objective of this study was to explore
      postpartum women's views and experiences with social support following
      childbirth. Four focus groups were conducted with an ethnically diverse sample of
      women (n = 33) in a large urban teaching hospital in New York City. Participants
      had completed participation in a postpartum depression randomized trial and were
      6-12 months postpartum. Data transcripts were reviewed and analyzed for themes.
      The main themes identified in the focus group discussions were mother's major
      needs and challenges postpartum, social support expectations and providers of
      support, how mothers mobilize support, and barriers to mobilizing support. Women
      across all groups identified receipt of instrumental support as essential to
      their physical and emotional recovery. Support from partners and families was
      expected and many women believed this support should be provided without asking.
      Racial/ethnic differences existed in the way women from different groups
      mobilized support from their support networks. Instrumental support plays a
      significant role in meeting women's basic needs during the postpartum period. In
      addition, women's expectations surrounding support can have an impact on their
      ability to mobilize support among their social networks. The results of this
      study suggest that identifying support needs and expectations of new mothers is
      important for mothers' recovery after childbirth. Future postpartum depression
      prevention efforts should integrate a strong focus on social support.

PMID- 22581379
TI  - Disparate patterns of prenatal care utilization stratified by medical and
      psychosocial risk.
AB  - To evaluate patterns of prenatal care utilization stratified by medical and
      psychosocial risk. A retrospective cohort of 786 pregnant women who subsequently
      delivered live births from 1999 to 2003 at the University of Michigan were
      classified into high medical, high psychosocial, high medical and high
      psychosocial (dual high risk) and low-risk pregnancies. Chi-square and logistic
      regression analyses assessed the association between risk and prenatal care
      utilization using the Kotelchuck Index. Of 786 pregnancies, 202 (25.7%) were high
      medical risk, 178 (22.7%) were high psychosocial risk, 227 (28.9%) were dual high
      risk and 179 (22.8%) were low-risk. Over 31% of dual high risk and 25% of high
      medical risk pregnancies received "adequate plus" prenatal care versus 10% of
      high psychosocial risk pregnancies. In multivariate analyses, adjusted for risk,
      race and insurance, high psychosocial risk pregnancies (OR = 1.69; 95% CI 1.06
      2.72) were significantly more likely to receive inadequate prenatal care than
      care of greater intensity. Many high psychosocial risk pregnancies do not receive
      adequate prenatal care.

PMID- 22581380
TI  - Parthenolide-induced apoptosis of hepatic stellate cells and anti-fibrotic
      effects in an in vivo rat model.
AB  - Parthenolide (PT), a sesquiterpene lactone derived from the plant feverfew, has
      pro-apoptotic activity in a number of cancer cell types. We assessed whether PT
      induces the apoptosis of hepatic stellate cells (HCSs) and examined its effects
      on hepatic fibrosis in an in vivo model. The effects of PT on rat HSCs were
      investigated in relation to cell growth inhibition, apoptosis, NF-kappaB binding
      activity, intracellular reactive oxygen species (ROS) generation, and glutathione
      (GSH) levels. In addition, the anti-fibrotic effects of PT were investigated in a
      thioacetamide-treated rat model. PT induced growth inhibition and apoptosis in
      HSCs, as evidenced by cell growth inhibition and apoptosis assays. PT increased
      the expression of Bax proteins during apoptosis, but decreased the expression of
      Bcl-2 and Bcl-X(L) proteins. PT also induced a reduction in mitochondrial
      membrane potential, poly(ADP-ribose) polymerase cleavage, and caspase-3
      activation. PT inhibited TNF-alpha-stimulated NF-kappaB binding activity in HSCs.
      The pro-apoptotic activity of PT in HSCs was associated with increased
      intracellular oxidative stress as evidenced by increased intracellular ROS levels
      and depleted intracellular GSH levels. Furthermore, PT ameliorated hepatic
      fibrosis significantly in a thioacetamide- treated rat model. In conclusion, PT
      exhibited pro-apoptotic effects in rat HSCs and ameliorated hepatic fibrosis in a
      thioacetamide-induced rat model.

PMID- 22581381
TI  - Localization of breast cancer resistance protein (Bcrp) in endocrine organs and
      inhibition of its transport activity by steroid hormones.
AB  - Breast cancer resistance protein (BCRP) is known for its protective function
      against the toxic effects of exogenous compounds. In addition to this, a role in
      the transport of endogenous compounds has been described. Since BCRP in the
      plasma membrane was shown to be regulated by sex steroids, we investigated the
      presence and possible role of BCRP in steroid hormone-producing organs.
      Therefore, the presence and localization of Bcrp was investigated in endocrine
      organs of wild-type mice. Furthermore, the interaction of various steroid
      hormones with human BCRP activity was studied. Quantitative PCR revealed Bcrp
      mRNA in the pituitary and adrenal glands, pancreas, ovary, testis and adipose
      tissue. Immunohistochemistry revealed the presence of Bcrp in the cortex of the
      adrenal gland and in plasma membranes of adipocytes. In the pituitary gland,
      pancreas, ovary and testis, Bcrp was mainly located in the capillaries. The
      interaction between BCRP and 12 steroid hormones was studied using membrane
      vesicles of HEK293-BCRP cells. Estradiol, testosterone, progesterone and
      androstenedione inhibited BCRP-mediated uptake of (3)H-estrone sulphate (E(1)S)
      most potently, with calculated inhibitory constant (Ki) values of 5.0 +/- 0.2, 36
      +/- 14, 14.7 +/- 1.3 and 217 +/- 13 MUM, respectively. BCRP function was
      attenuated non-competitively, which implies an allosteric inhibition of BCRP
      mediated E(1)S transport by these steroids. In conclusion, localization of Bcrp
      in endocrine organs together with the efficient allosteric inhibition of the
      efflux pump by steroid hormones are suggestive for a role for BCRP in steroid
      hormone regulation.

PMID- 22581383
TI  - VACM-1/cul5 expression in vascular tissue in vivo is induced by water deprivation
      and its expression in vitro regulates aquaporin-1 concentrations.
AB  - VACM-1, a cul5 gene product, when overexpressed in vitro, has an
      antiproliferative effect. In vivo, VACM-1/cul5 is present in tissues involved in
      the regulation of water balance. Neither proteins targeted for VACM-1/cul5
      specific degradation nor factors that may regulate its expression in those
      tissues have been studied. To identify genes that may be misregulated by VACM-1
      cDNA, we performed microarray analysis. Our results indicate that in cos-1 cells
      transfected with VACM-1 cDNA, mRNA levels for several genes, including AQP1, were
      decreased when compared to the control group. Our results also indicate that in
      cos-1 cells transfected with VACM-1 cDNA, endogenous AQP1 protein was decreased
      about 6-fold when compared to the controls. To test the hypothesis that VACM
      1/cul5 may be regulated by conditions that compromise water homeostasis in vivo,
      we determined if 24 h of water deprivation affects VACM-1/cul5 levels or the
      effect of VACM-1/cul5 on AQP1. VACM-1 mRNA and protein levels were significantly
      higher in rat mesenteric arteries, skeletal muscle and the heart ventricle but
      not in the heart atrium from 24-h water-deprived rats when compared to the
      controls. Interestingly, 24 h of water deprivation increased modification of VACM
      1 by an ubiquitin-like protein, Nedd8, essential for cullin-dependent E3 ligase
      activity. Although water deprivation did not significantly change AQP1 levels in
      the mesenteric arteries, AQP1 protein concentrations were inversely correlated
      with the ratio of the VACM-1 to Nedd8-modified VACM-1. These results suggest that
      VACM-1/cul5 may regulate endothelial AQP1 concentration both in vivo and in
      vitro.

PMID- 22581384
TI  - Role of phospholipase A2s and lipid mediators in secondary damage after spinal
      cord injury.
AB  - Inflammation is considered to be an important contributor to secondary damage
      after spinal cord injury (SCI). This secondary damage leads to further
      exacerbation of tissue loss and functional impairments. The immune responses that
      are triggered by injury are complex and are mediated by a variety of factors that
      have both detrimental and beneficial effects. In this review, we focus on the
      diverse effects of the phospholipase A(2) (PLA(2)) superfamily and the downstream
      pathways that generate a large number of bioactive lipid mediators, some of which
      have pro-inflammatory and demyelinating effects, whereas others have anti
      inflammatory and pro-resolution properties. For each of these lipid mediators, we
      provide an overview followed by a discussion of their expression and role in SCI.
      Where appropriate, we have compared the latter with their role in other
      neurological conditions. The PLA(2) pathway provides a number of targets for
      therapeutic intervention for the treatment of SCI and other neurological
      conditions.

PMID- 22581382
TI  - Immunohistochemical localization of the NH(2)-terminal and COOH-terminal
      fragments of dentin sialoprotein in mouse teeth.
AB  - Dentin sialoprotein (DSP) is a major non-collagenous protein in dentin. Mutation
      studies in human, along with gene knockout and transgenic experiments in mice,
      have confirmed the critical role of DSP for dentin formation. Our previous study
      reported that DSP is processed into fragments in mouse odontoblast-like cells. In
      order to gain insights into the function of DSP fragments, we further evaluated
      the expression pattern of DSP in the mouse odontoblast-like cells using
      immunohistochemistry and western blot assay with antibodies against the NH(2)
      terminal and COOH-terminal regions of DSP. Then, the distribution profiles of the
      DSP NH(2)-terminal and COOH-terminal fragments and osteopontin (OPN) were
      investigated in mouse teeth at different ages by immunohistochemistry. In the
      odontoblast-like cells, multiple low molecular weight DSP fragments were
      detected, suggesting that part of the DSP protein was processed in the
      odontoblast-like cells. In mouse first lower molars, immunoreactions for anti-DSP
      NH(2) antibody were intense in the predentin matrix but weak in mineralized
      dentin; in contrast, for anti-DSP-COOH antibody, strong immunoreactions were
      found in mineralized dentin, in particular dentinal tubules but weak in
      predentin. Therefore, DSP NH(2)-terminal and COOH-terminal fragments from
      odontoblasts were secreted to different parts of teeth, suggesting that they may
      play distinct roles in dentinogenesis. Meanwhile, both DSP antibodies showed weak
      staining in reactionary dentin (RD), whereas osteopontin (OPN) was clearly
      positive in RD. Therefore, DSP may be less crucial for RD formation than OPN.

PMID- 22581385
TI  - A review of the elements of human well-being with an emphasis on the contribution
      of ecosystem services.
AB  - Natural ecosystems perform fundamental life-support services upon which human
      civilization depends. However, many people believe that nature provides these
      services for free and therefore, they are of little or no value. While we do not
      pay for them, we pay significantly for their loss in terms of wastewater
      treatment facilities, moratoriums on greenhouse gases, increased illnesses,
      reduced soil fertility and losses in those images of nature that contribute to
      our basic happiness. Little is understood about the well-being benefits of the
      natural environment and its ecosystem services. The interwoven relationship of
      ecosystems and human well-being is insufficiently acknowledged in the wider
      philosophical, social, and economic well-being literature. In this article, we
      discuss an approach to examine human well-being and the interactions of its four
      primary elements-basic human needs, economic needs, environmental needs, and
      subjective well-being-and ecosystem services.

PMID- 22581386
TI  - Even-aged and uneven-aged forest management in boreal Fennoscandia: a review.
AB  - Since WWII, forest management in Fennoscandia has primarily been based on even
      aged stand management, clear cut harvesting and thinning from below. As an
      alternative, uneven-aged management, based on selection cutting of individual
      trees or small groups of trees, has been proposed. In this review we discuss the
      theoretical aspects of ecology and economics of the two management approaches. We
      also review peer-reviewed studies from boreal Fennoscandia, which have aimed at
      comparing the outcomes of uneven-aged and the conventional even-aged forest
      management. According to a common view the main obstacle of practicing uneven
      aged forestry is its low economic performance. However, the reviewed studies did
      not offer any straightforward support for this view and several studies have
      found uneven-aged management to be fully competitive with existing even-aged
      management. Studies on the ecological aspects indicated that selection cuttings
      maintain mature or late-successional forest characteristics and species
      assemblages better than even-aged management, at least at the stand scale and in
      the short term. We conclude that although the number of relevant studies has
      increased in recent years, the ecological and economic performance of alternative
      management methods still remains poorly examined, especially for those stands
      with multiple tree species and also at wider spatial and temporal scales. For
      future research we advocate a strategy that fully takes into consideration the
      interdisciplinary nature of forest management and is better connected to social
      goals and latest theoretical and methodological developments in ecology and
      economics.

PMID- 22581387
TI  - Clinical significance of amphiregulin and epidermal growth factor in colostrum.
AB  - BACKGROUND: Colostrum contains a wide variety of crucial nutritional elements
      including growth factors for newborn infants to adapt to the extrauterine
      environment. OBJECTIVE: To investigate the clinical significance of epidermal
      growth factor receptor ligands in milk during the first month of lactation.
      METHODS: The concentrations of epidermal growth factor (EGF), amphiregulin (AR)
      and transforming growth factor-alpha (TGF-alpha) in milk sampled from a total of
      31 normal mothers at days 1-3, 5, and 30 postpartum were examined using ELISA.
      RESULTS: At days 1-3, the concentration of EGF was extremely high [131.6 +/- 20.4
      (mean +/- SEM) ng/ml] compared to that of AR (4,197.2 +/- 1,055.2 pg/ml) or TGF
      alpha (261.7 +/- 33.6 pg/ml), while the concentration of AR was significantly
      elevated compared to that of TGF-alpha. At days 5 and 30, the concentration of
      EGF was significantly elevated compared to that of AR or TGF-alpha. In 16 mothers
      among the same 31 subjects, samples were longitudinally obtained on days 1, 2, 5,
      and 30 postpartum. Concentrations of AR were higher on days 1 and 2 and rapidly
      declined to below 1 ng/ml on day 5, and were maintained at lower levels on day
      30. Concentrations of EGF were high on day 1 (greater than 10 ng/ml) but
      gradually declined by days 2, 5, and 30. Concentrations of TGF-alpha remained at
      lower levels of below 1 ng/ml throughout the lactation period from days 1 to 30.
      CONCLUSION: These results suggested that EGF and amphiregulin in colostrum might
      contribute to the early stage of development of neonatal gastrointestinal
      function.

PMID- 22581388
TI  - Nifedipine versus labetalol in the treatment of hypertensive disorders of
      pregnancy.
AB  - PURPOSE: To assess the maternal and fetal outcomes of pregnancies affected by
      hypertensive disorders treated with nifedipine versus labetalol. METHODS: A
      retrospective study in hypertensive patients treated during pregnancy with
      nifedipine or labetalol was conducted. After the charts review the patients were
      divided in the four groups: gestational hypertension (113 patients); mild
      preeclampsia (77 patients); severe preeclampsia (31 patients); HELLP syndrome (21
      patients). The pregnancy and neonatal records were analyzed by paired and
      unpaired t test. RESULTS: We found that there was an higher rate of intrauterine
      growth restriction infants among women treated with labetalol compared with those
      treated with nifedipine (38.8 vs. 15.5 %; p < 0.05), but only in the subgroup of
      women affected by Gestational Hypertension and Mild Preeclampsia. In this group
      was also higher the rate of fetal worsening assessed by fetal heart rate tracing
      (33.3 vs. 14.2 %; p < 0.05). No neonatal malformations and no differences in the
      rate of adverse side effects were observed. CONCLUSIONS: Antihypertensive therapy
      in pregnancy with Labetalol may have the potential to impair fetal behavior in
      low degrees hypertensive diseases of pregnancy. Optimal care must balance the
      potentially conflicting risks and benefits to mother and fetus.

PMID- 22581389
TI  - Controlled synthesis, characterization, and application of iron oxide
      nanoparticles for oral delivery of insulin.
AB  - Impurity-free, controlled synthesis of iron oxide nanoparticle, in ultrapure
      water and chitosan, using laser ablation technique and its application for type
      II diabetes management through oral delivery of insulin-loaded iron oxide
      chitosan nanocomposite is presented. The purity of the nanoparticle is monitored
      by laser-induced breakdown spectroscopy technique. The synthesized iron oxide
      nanoparticle was characterized by UV/Vis absorption spectroscopy, and
      morphological study was performed by scanning electron microscope. The intensity
      of absorption peak and wavelength corresponding to peak of the nanoparticle
      prepared in water and chitosan is dependent on the laser energy used for ablation
      purpose. Red shift in the absorption peak wavelength was observed by increasing
      laser energy. In addition to red shift, an increase in intensity of absorption
      peak was also seen when ablating laser energy was increased. The appearance of a
      weak peak around 295 nm was observed in iron oxide-chitosan nanocomposite. The
      spherical shape of the nanoparticle synthesized at the lower laser energy has
      gradually changed to triangular and irregular shaped structures as ablating laser
      energy was increased. The spherical nanoparticles loaded with insulin were used
      for oral delivery for diabetic management. The iron oxide-chitosan nanocomposite
      loaded with insulin has resulted in reduction in blood glucose level in mild
      diabetic, subdiabetic, and severely diabetic rats; more than 51 % reduction in
      blood glucose level, compared to the control group, has been achieved in the
      present work.

PMID- 22581390
TI  - Laser light activation of a second-generation photosensitiser and its use as a
      potential photomodulatory agent in skin rejuvenation.
AB  - Photodynamic rejuvenation therapy (PDRT) is a growing field in cosmetic
      dermatology. In this study, different sources of light (a yellow laser, a red
      laser and ultraviolet A (UVA) lamps) were used to activate a second-generation
      photosensitiser, hypericin. Uptake of hypericin was monitored over 24 h and
      efficacy of PDRT was assessed using cell viability and reactive oxygen species
      (ROS) quantification assays. In addition, we show for the first time, a
      quantifiable assay for ROS production in human dermal fibroblasts incubated with
      hypericin and exposed to yellow laser light or UVA lamps. Furthermore, we
      optimised a protocol with regard to hypericin concentration and irradiation
      parameters using the XTT cell viability kit. This study showed that this
      photosensitiser, hypericin, was taken up by the cells in a concentration
      dependent manner over 24 h with cell saturation occurring after approximately 16
      h. The uptake seemed to be localised to the cell cytoplasm with no hypericin
      appearing in the nucleus. The levels of ROS increased in the cell when irradiated
      with the yellow laser (561 nm) however, it did not increase further with the
      addition of hypericin. Hypericin and UVA showed a significant increase in the
      amount of ROS produced. The results also show that cell viability is not affected
      by low power light (2 mW) from the yellow laser irrespective of the dose used.
      However, an increase to 10 mW power with 5 J/cm(2) light dose, resulted in a
      significant drop (p < 0.05) in cell viability at both 0.5 (77.53 +/- 9.67 %) and
      1 MUM (48.51 +/- 13.27 %) hypericin concentrations. In contrast, a 20 % increase
      in cell viability was seen with 1 J/cm(2) and 20 mW and 0.25 MUM hypericin.
      Overall, this study highlights an optimised protocol for hypericin-induced
      photorejuvenative therapy using laser light and proposes that parameters of 0.25
      MUM hypericin as a photosensitiser activated via a dosage of 1 J/cm(2) yellow
      laser light produces an effective in vitro outcome to be considered as an
      important contribution towards optimising PDRT.

PMID- 22581391
TI  - A placebo-controlled study to assess Standardized Field Sobriety Tests
      performance during alcohol and cannabis intoxication in heavy cannabis users and
      accuracy of point of collection testing devices for detecting THC in oral fluid.
AB  - RATIONALE: Standardized Field Sobriety Tests (SFST) and oral fluid devices are
      used to screen for driving impairment and roadside drug detection, respectively.
      SFST have been validated for alcohol, but their sensitivity to impairment induced
      by other drugs is relatively unknown. The sensitivity and specificity for
      Delta(9)-tetrahydrocannabinol (THC) of most oral fluid devices have been low.
      OBJECTIVE: This study assessed the effects of smoking cannabis with and without
      alcohol on SFST performance. Presence of THC in oral fluid was examined with two
      devices (Drager Drug Test(r) 5000 and Securetec Drugwipe(r) 5). METHODS: Twenty
      heavy cannabis users (15 males and 5 females; mean age, 24.3 years) participated
      in a double-blind, placebo-controlled study assessing percentage of impaired
      individuals on the SFST and the sensitivity of two oral fluid devices.
      Participants received alcohol doses or alcohol placebo in combination with 400
      MUg/kg body weight THC. We aimed to reach peak blood alcohol concentration values
      of 0.5 and 0.7 mg/mL. RESULTS: Cannabis was significantly related to performance
      on the one-leg stand (p = 0.037). Alcohol in combination with cannabis was
      significantly related to impairment on horizontal gaze nystagmus (p = 0.029). The
      Drager Drug Test(r) 5000 demonstrated a high sensitivity for THC, whereas the
      sensitivity of the Securetec Drugwipe(r) 5 was low. CONCLUSIONS: SFST were mildly
      sensitive to impairment from cannabis in heavy users. Lack of sensitivity might
      be attributed to tolerance and time of testing. SFST were sensitive to both doses
      of alcohol. The Drager Drug Test(r) 5000 appears to be a promising tool for
      detecting THC in oral fluid as far as correct THC detection is concerned.

PMID- 22581393
TI  - [2]Pseudorotaxanes, [2]rotaxanes and metal-organic rotaxane frameworks containing
      tetra-substituted dibenzo[24]crown-8 wheels.
AB  - [2]Pseudorotaxanes, [2]rotaxanes and metal-organic rotaxane framework materials
      that utilise DB24C8 as the wheel component are well known and structural
      variations based on changing the axle component are common. Studies in which the
      DB24C8 wheel is structurally modified are much more limited. Herein, is described
      the synthesis of symmetrical DB24C8 analogues containing four CH(2)OR (R =
      CH(2)CH(2)CH(3), CH(2)(C(6)H(5)), C(6)H(5) and C(6)H(4)(4-COOEt)) substituents on
      the 4 and 5 positions of the aromatic rings. The effect of these molecular
      appendages on the stability and structures of the interpenetrated and interlocked
      molecules derived from these new wheels is described. The major effects are an
      increase in association constants for the formation of [2]pseudorotaxanes
      relative to DB24C8, the crystal packing of [2]rotaxanes and a change on the
      internal structure of a 2D MORF (R = C(6)H(5)) compared to DB24C8.

PMID- 22581392
TI  - Increased drinking after intra-striatal injection of the dopamine D2/D3 receptor
      agonist quinpirole in the rat.
AB  - RATIONALE: Dopamine D2 receptor hyperactivity has been implicated in the
      development of psychogenic polydipsia in schizophrenic patients. Repeated
      treatment with dopamine agonists, including the D2/D3 agonist quinpirole, has
      been shown to induce hyperdipsia in a number of animal models. Despite these
      observations, obtained with systemic administrations, little attempt has been
      made to investigate where in the brain dopamine agonists act to induce
      hyperdipsia. OBJECTIVE: The present study investigates the effects of repeated
      intra-caudate infusions of quinpirole on the intake of water by rats tested under
      free-drinking conditions. MATERIALS AND METHODS: Rats with bilateral cannulae
      placed into the anterior, central or posterior caudate received quinpirole
      microinfusions (1 MUg/side) for five consecutive days in their home cage. Water
      intake was measured 15 and 60 min after the treatment. RESULTS: When injected in
      the central caudate, quinpirole increased water intake, and this effect
      progressively increased over sessions, indicating the development of
      sensitization. When injected in the posterior caudate, the dipsogenic effect of
      quinpirole was less intense and did not undergo sensitization. The infusion of
      quinpirole in the anterior caudate did not affect drinking. CONCLUSION: The
      present study shows that caudate D2/3 receptors play an important role in the
      development of quinpirole-induced hyperdipsia, an animal model of psychotic
      polydipsia.

PMID- 22581394
TI  - Ultrasonographic studies on ovarian dynamics and associated estrus manifestations
      of jennies under controlled management, Ethiopia.
AB  - A serial ultrasonographic study was conducted on nine jennies aged 5-15 years
      from January to April 2008 with the objective of studying ovarian follicular
      dynamics and estrus manifestations under controlled management. Ovarian
      follicular activity was determined from the number and size distribution of
      follicles, length of interovulatory interval (IOI), growth rate of preovulatory
      follicles, diameter of follicles at the onset of estrus, and incidence of
      ovulation. Estrus manifestations were characterized using length of estrus and
      estrous cycle. The mean (+/- SD) number of follicle detected per ovary was 5.45
      +/- 2.3 (range, 1-16) with sizes ranging from 2.9 to 44 mm. The mean (+/- SD)
      size of follicle encountered at the onset of estrus was 25.9 +/- 3.7 mm (range,
      20.9-34.4) while that of the preovulatory follicles at -1 day before ovulation
      was 36.81 +/- 3.78 mm. The mean (+/- SD) IOI, estrus, and estrous cycle length
      were 25.4 +/- 33.6, 7.9 +/- 32.9, and 24.2 +/- 37.4 days, respectively. The mean
      (+/- SD) growth rate of the preovulatory follicle after the day of divergence was
      1.9 +/- 30.3 mm/day. Serum progesterone profile followed the same patterns of
      ovarian dynamics with maximum values being detected during midluteal phase. Serum
      progesterone assay revealed blood progesterone profiles of <1.0 ng/ml during
      estrus and up to 11 ng/ml during midluteal phase with a pattern following
      follicular dynamics. Body condition of the study jennies steadily increased and
      was positively correlated (r = 0.52, p < 0.001) with the diameter of the
      preovulatory follicle. In conclusion, the ultrasonic evaluation has revealed that
      follicular dynamics of jennies were generally related with body condition which
      might have been influenced by the type of management.

PMID- 22581395
TI  - Antihypertensive treatment and sexual dysfunction.
AB  - Sexual dysfunction is frequently encountered in hypertensive patients. Available
      data indicates that sexual dysfunction is more frequent in treated than in
      untreated patients, generating the hypothesis that antihypertensive therapy might
      be associated with sexual dysfunction. Several lines of evidence suggest that
      differences between antihypertensive drugs exist regarding their effects on
      sexual function. Older antihypertensive drugs (diuretics, beta blockers) exert
      detrimental effects on erectile function whereas newer drugs (nebivolol,
      angiotensin receptor blockers) have neutral or even beneficial effects.
      Phosphodiesterase (PDE)-5 inhibitors are effective in hypertensive patients and
      can be safely administered even when multidrug regimes are used. Precautions need
      to be taken with alpha blockers or patients with uncontrolled high-risk
      hypertension, while co-administration with nitrates is contraindicated.

PMID- 22581398
TI  - Comment on Tong et al.: Two-stage procedure protocol for minimally invasive plate
      osteosynthesis technique in the treatment of the complex pilon fracture.

PMID- 22581397
TI  - A distal femoral supra-condylar plate: biomechanical comparison with condylar
      plate and first clinical application for treatment of supracondylar fracture.
AB  - PURPOSE: An anatomical supra-condylar plate is designed and analysed by
      biomechanical testing. METHODS: The biomechanical properties of the supra
      condylar and condylar plate were compared in six matched pairs of cadaveric
      femurs. A transverse osteotomy gap was created to simulate an OTA/AO type A3
      supracondylar fracture. The left and right specimens were fitted with supra
      condylar and condylar plate, respectively. Nondestructive axial compression,
      three-point bending and torsion tests were performed, and the peak load of the
      bone-implant construction was measured. The fracture site suitable for supra
      condylar plate application and its correlation with femoral length were
      calculated. The gender influence on it was also discussed. RESULTS: The
      difference of stiffness between the supra-condylar and condyle groups were not
      significant (P > 0.05) at 363.4 and 362.5 N/mm for compression, 229.5 and 237.6
      N/mm in the sagittal plane and 195.5 and 188.4 N/mm in the coronal plane for
      three-point bending, and 7.5 and 7.9 Nm/deg for axial torsion, respectively. The
      peak load was 4438 +/- 136.15 N and 5215 +/- 174.33 N, respectively, for the two
      groups. The average extent of the fracture site suitable for the application of
      the supra-condylar plate was 70.86 +/- 4.61 mm. The femoral length and gender
      showed no influence on it. CONCLUSION: Despite the limited bone contact area
      provided by the supra-condylar plate, its construct stiffness is comparable to
      the condylar plate. The supra-condylar plate can be used to treat carefully
      selected extra-articular supracondylar fractures.

PMID- 22581399
TI  - Prominent corneal nerves: a novel sign of lipoid proteinosis.
AB  - AIM: Detailed longitudinal evaluation of corneal and other ophthalmological
      features of patients with lipoid proteinosis (LP). METHODS: Ophthalmological
      examinations, chart review, ultrasound biomicroscopy, corneal confocal
      microscopic examinations with Nidek confoScan 4 and direct sequencing of the
      extracellular matrix protein 1 gene in individuals from three consanguineous
      Saudi families with LP. RESULTS: Seven individuals affected with LP (four female
      and three male subjects) were evaluated together with nine unaffected parents and
      siblings. All affected individuals had homozygous mutations in extracellular
      matrix protein 1. Four patients were examined frequently (every 6 months)
      beginning in infancy and early childhood. Globe and vision were normal in all
      individuals, and moniliform blepharosis always appeared after the age of 4 years.
      Prominent corneal nerves were detected in all patients regardless of age and were
      more apparent in patients with more severe genetic mutations. Conversely, the
      severity of moniliform blepharosis seemed age-dependent rather than genotype
      related. CONCLUSION: Prominent corneal nerves can be helpful in the early
      diagnosis of LP and should be added to the list of LP ophthalmological diagnostic
      features.

PMID- 22581400
TI  - Cyclodeviation of the retinal vascular arcades: an accessory sign of ocular
      torsion.
AB  - Assessment of ocular torsion via fundus examination is an important tool for
      diagnosis and management of cyclorotational disorders. The widely used disc
      macula relationship for quantification of ocular torsion possesses inherent
      limitations, which restricts its use in some clinical scenarios. An accessory
      technique of fundus examination for assessing torsion is hereby proposed using
      vascular cues. Retinal blood vessels share common guidance signals with ganglion
      cell axons and are now recognised to follow retinal axonal pathways.
      Identification of the axis of the retinal vascular arcades can serve as a direct
      and accessory means to provide additional pertinent information regarding ocular
      cyclorotations.

PMID- 22581401
TI  - Valproic acid treatment may be harmful in non-dominant forms of retinitis
      pigmentosa.

PMID- 22581403
TI  - Abstracts of the 99th Annual Congress of the Swiss Society of Surgery. June 20
      22, 2012. Davos, Switzerland.

PMID- 22581402
TI  - Glucose released by hydrolytic activity of amylase influences the pigment
      synthesis in Penicillium sp NIOM-02.
AB  - Carbon catabolite repression is generally considered as a regulatory mechanism to
      ensure sequential synthesis of secondary metabolites. In this study we made an
      attempt to understand the influence of amylase activity on pigment synthesis in
      Penicillium sp NIOM-02. The amylase activity is inversely proportional to pigment
      production. The high performance liquid chromatography analysis of amylase
      reaction revealed glucose as the major product of starch hydrolysis. The fungus
      grown in acarbose (inhibitor of amylase) incorporated media produced higher
      quantities of pigments. Apparently, glucose released due to amylase activity
      influenced the pigment synthesis by cAMP signaling pathway.

PMID- 22581404
TI  - Protein isolation from blue mussels (Mytilus edulis) using an acid and alkaline
      solubilisation technique--process characteristics and functionality of the
      isolates.
AB  - BACKGROUND: The pH shift method was developed to isolate proteins from low-value
      raw materials by solubilisation at high or low pH followed by precipitation. In
      this paper the application of the pH shift method on isolated mussel (Mytilus
      edulis) meat and whole mussels is reported. RESULTS: Highest protein
      solubilisation was achieved at pH values of 2.6 and 12. The optimum precipitation
      pH values were established as around 5.8 following acid solubilisation and 5.2
      following alkaline solubilisation. Protein recoveries were 430 and 580 g kg(-1)
      with the acid and alkaline processes respectively. Using whole crushed mussels,
      the corresponding recoveries were 310 and 480 g kg(-1). Process modifications to
      further improve protein recovery resulted in only a marginal increase. Lipid
      oxidation was not induced during pH shift processing, but heavy proteolysis
      occurred during the acid process version. Proteolysis could not be prevented by
      porcine plasma protein. Alkali-produced proteins performed better in all
      functionality tests compared with acid-produced proteins. The acid process
      removed slightly more lipids, recovered relatively more cysteine, methionine and
      lysine and resulted in whiter isolates. CONCLUSION: The pH shift method can be
      successfully used to extract functional proteins from mussels and add value to
      blue mussels unsuitable for human consumption (with or without shells).

PMID- 22581405
TI  - A cross-lagged model of the development of ADHD inattention symptoms and rapid
      naming speed.
AB  - Although previous research has identified contemporaneous associations between
      cognitive deficits and symptom phenotypes in Attention Deficit/Hyperactivity
      Disorder, no studies have as yet attempted to identify direction of effect. The
      present study used cross-lagged path modeling to examine competing hypotheses
      about longitudinal associations between rapid naming speed and symptoms of
      inattention in children. 1,506 school-age twins from Australia and the U.S. were
      tested for inattention, hyperactivity/impulsivity, and rapid naming speed at
      three and four time points, respectively. Symptom severity of inattention from
      Kindergarten to fourth grade is consistently predicted by previous rapid naming,
      over and above auto-regressive and correlational associations in the model.
      Likewise, inattention symptoms have a small but significant predictive effect on
      subsequent rapid naming. The findings support a reciprocal relationship between
      naming speed and ADHD inattentive symptoms.

PMID- 22581406
TI  - Virus-based piezoelectric energy generation.
AB  - Piezoelectric materials can convert mechanical energy into electrical energy, and
      piezoelectric devices made of a variety of inorganic materials and organic
      polymers have been demonstrated. However, synthesizing such materials often
      requires toxic starting compounds, harsh conditions and/or complex procedures.
      Previously, it was shown that hierarchically organized natural materials such as
      bones, collagen fibrils and peptide nanotubes can display piezoelectric
      properties. Here, we demonstrate that the piezoelectric and liquid-crystalline
      properties of M13 bacteriophage (phage) can be used to generate electrical
      energy. Using piezoresponse force microscopy, we characterize the structure
      dependent piezoelectric properties of the phage at the molecular level. We then
      show that self-assembled thin films of phage can exhibit piezoelectric strengths
      of up to 7.8 pm V(-1). We also demonstrate that it is possible to modulate the
      dipole strength of the phage, hence tuning the piezoelectric response, by
      genetically engineering the major coat proteins of the phage. Finally, we develop
      a phage-based piezoelectric generator that produces up to 6 nA of current and 400
      mV of potential and use it to operate a liquid-crystal display. Because
      biotechnology techniques enable large-scale production of genetically modified
      phages, phage-based piezoelectric materials potentially offer a simple and
      environmentally friendly approach to piezoelectric energy generation.

PMID- 22581407
TI  - Piezoelectric devices: Squeezed virus produces electricity.

PMID- 22581409
TI  - Bladder capacity on preoperative urodynamics may impact outcomes on
      transobturator male slings.
AB  - AIMS: Stress incontinence is frequently seen after prostate surgery. We sought to
      evaluate preoperative urodynamic (UDS) parameters on functional outcomes after
      transobturator male sling placement. METHODS: 49 male patients with stress
      urinary incontinence (SUI) after radical prostatectomy or transurethral resection
      of the prostate underwent transobturator sling (TOS) placement from December 2008
      through June 2011 (AdVance(r) and Virtue(r)). A retrospective review was
      performed of those patients who underwent preoperative UDS and had a minimum of 6
      weeks of follow up. In total 38 patients were identified. There were 28 patients
      considered a success and 10 patients considered a failure. We then evaluated the
      preoperative UDS parameters between these two groups to identify potential
      adverse parameters. RESULTS: Overall success rate was 74% (28/38) with an average
      follow up of 3 months. Comparing the success and failure groups there was no
      difference between the pre-operative parameters. On pre-operative UDS, only
      bladder capacity was found to be significantly lower in those who failed TOS.
      Univariate comparisons of sling outcomes stratified by bladder capacity tertiles
      was performed. These values were chosen as they represented the 25th, 50th, and
      75th percentiles, respectively. All patients (10/10) with bladder capacities in
      the top tertile experienced success with the sling, compared to only 62% and 50%
      of patients in the 50th and 25th tertiles, respectively; these differences were
      significant (Fisher's exact P-value = 0.044). CONCLUSION: TOS is an effective
      therapy for men with SUI. Bladder capacity based on pre-operative UDS may impact
      the success of the procedure.

PMID- 22581408
TI  - Implementation of a biotechnological process for vat dyeing with woad.
AB  - The traditional process for vat dyeing with woad (Isatis tinctoria L.) basically
      relies on microbial reduction of indigo to its soluble form, leucoindigo, through
      a complex fermentative process. In the 19th century, cultivation of woad went
      into decline and use of synthetic indigo dye and chemical reduction agents was
      established, with a consequent negative impact on the environment due to the
      release of polluting wastewaters by the synthetic dyeing industry. Recently, the
      ever-growing demand for environmentally friendly dyeing technologies has led to
      renewed interest in ecological textile traditions. In this context, this study
      aims at developing an environmentally friendly biotechnological process for vat
      dyeing with woad to replace use of polluting chemical reduction agents. Two
      simple broth media, containing yeast extract or corn steep liquor (CSL), were
      comparatively evaluated for their capacity to sustain the growth and reducing
      activity of the strain Clostridium isatidis DSM 15098(T). Subsequently, the
      dyeing capacity of the CSL medium added with 140 g L-1 of woad powder, providing
      2.4 g L-1 of indigo dye, was evaluated after fermentation in laboratory
      bioreactors under anaerobic or microaerophilic conditions. In all fermentations,
      a sufficiently negative oxidation/reduction potential for reduction of indigo was
      reached as early as 24 h and maintained up to the end of the monitoring period.
      However, clearly faster indigo dye reduction was seen in the broth cultures
      fermented under strict anaerobiosis, thus suggesting the suitability of the N2
      flushing strategy for enhancement of bacterial-driven indigo reduction.

PMID- 22581410
TI  - One-pot fabrication of noble-metal nanoparticles that are encapsulated in hollow
      silica nanospheres: dual roles of poly(acrylic acid).
AB  - An efficient and facile one-pot method was developed to fabricate noble-metal
      nanoparticles (NMNs; Au, Pt, PdO and Ag) that were encapsulated within hollow
      silica nanospheres (HSNs; NMNs@HSNs) with a size of about 100 nm. NMNs@HSNs were
      afforded in very high yields between 85-95 %. Poly(acrylic acid) (PAA)
      polyelectrolyte played a dual role in the fabrication process, both as a core
      template of the HSNs and as a captor of the NMNs through coordination
      interactions between the COO(-) groups on the ammonium polyacrylate (APA)
      polyanionic chains and the empty orbital of the Au atom. The amount of Au loading
      in Au@HSNs was easily regulated by varying the volume of the HAuCl(4) solution
      added. In addition, these rattle-type particles were successfully applied in the
      catalytic reduction of 2-nitroaniline (2-NA) as a model reaction, thus indicating
      that the micropores in the silica shell could achieve the transport of small
      species--with a size smaller than that of the micropores--into the cavity. Thus,
      these fabricated NMNs@HSNs have promising applications in catalysis.

PMID- 22581411
TI  - Gadoxetic acid-enhanced T1-weighted MR cholangiography in primary sclerosing
      cholangitis.
AB  - PURPOSE: To investigate the value of gadoxetic acid-enhanced three-dimensional T1
      weighted MR cholangiography (T1w-MRC) in comparison to three-dimensional T2
      weighted MR cholangiopancreaticography (T2w-MRCP) in patients with primary
      sclerosing cholangitis (PSC). MATERIALS AND METHODS: Thirty-four MR exams in 29
      patients (46.0 +/- 16.1 years; 19 men, 10 women) scanned within a 14-month period
      were retrospectively included. Two abdominal radiologists independently evaluated
      image quality regarding image contrast, image quality degradation due to
      artifacts, and visualization quality of ducts. The order of biliary tree branches
      that were visualized and reader preference toward each method were recorded.
      Helpfulness of T1w-MRC was scored in consensus. Confirmatory endoscopic
      retrograde cholangiopancreaticography (ERCP) performed within 3 months of the MR
      examination was available in 8 patients. RESULTS: Image quality of T1w-MRC and
      T2w-MRCP was graded good to excellent in all cases. There were advantages for
      both T1w-MRC (functional information, less degradation due to artifacts) and T2w
      MRCP (higher order of visualized branches, better branch depiction). Both readers
      showed preference for T2w-MRCP; however, both readers found gadoxetic acid
      enhanced T1w-MRC helpful in the majority of cases. CONCLUSION: Gadoxetic acid
      enhanced T1w-MRC is complementary to, but should not replace, T2w-MRCP. T1w-MRC
      is a useful adjunct to T2w-MRCP for morphologic evaluation and provides
      additional diagnostic information.

PMID- 22581412
TI  - Associations between household and neighborhood income and anxiety symptoms in
      young adolescents.
AB  - BACKGROUND: A better understanding of the role of both family- and neighborhood
      level socioeconomic characteristics in the development of anxiety disorders is
      important for identifying salient target populations for intervention efforts.
      Little research has examined the question of whether associations between anxiety
      and socioeconomic status (SES) differ depending upon the level at which SES is
      measured or way in which anxiety manifests. We studied associations between both
      household- and neighborhood-level income and four different manifestations of
      anxiety in a community sample of young adolescents. METHODS: We conducted a cross
      sectional analysis of data on 498 subjects aged 11-13 from a cohort study of
      Seattle-area middle school students. Generalized estimating equations were used
      to examine the association between both annual household income and neighborhood
      median income and each of four anxiety subscale scores from the multidimensional
      anxiety scale for children (MASC): physical symptoms, harm avoidance, social
      anxiety, and separation/panic anxiety. RESULTS: A negative association was found
      between household income and scores on two of the four MASC subscales--physical
      symptoms and separation/panic anxiety. In contrast, at equivalent levels of
      household income, adolescents living in higher income neighborhoods reported
      higher physical and harm avoidance symptom scores. CONCLUSION: The role that SES
      plays in the development of childhood anxiety appears to be complex and to differ
      depending on the specific type of anxiety that is manifest and whether income is
      evaluated at the household or neighborhood level.

PMID- 22581414
TI  - Non-invasive fractional flow reserve: scientific basis, methods and perspectives.

PMID- 22581415
TI  - Oxidative stress in the cardiorenal metabolic syndrome.
AB  - Excess visceral adiposity contributes to inappropriate activation of the renin
      angiotensin-aldosterone system despite a state of volume expansion and of salt
      retention that contributes to subclinical elevations of pro-oxidant mechanisms.
      These adverse effects are mediated by excess generation of reactive oxygen
      species (ROS) and diminished antioxidant defense mechanisms. Excess tissue (i.e.,
      skeletal muscle, liver, heart) free oxygen radicals contribute to impairments in
      the insulin-dependent metabolic signaling pathways that regulate glucose
      utilization/disposal and systemic insulin sensitivity. The generation of ROS is
      required for normal cell signaling and physiological responses. It is a loss of
      redox homeostasis that results in a proinflammatory/profibrotic milieu that
      promotes impairments in insulin metabolic signaling, reduced endothelial-mediated
      vasorelaxation, and associated cardiovascular and renal structural and functional
      abnormalities. These maladaptive processes are increasingly recognized as
      important in the progression of hypertension in the cardiorenal metabolic
      phenotype. There is increasing evidence to support a critical role for Ang II
      signaling through the AT(1)R and aldosterone actions through the MR in
      conjunction with an altered redox-mediating impaired endothelial, cardiac and
      renal function in this metabolic phenotype. There are emerging clinical data that
      indicate that therapies that target the renin angiotensin-aldosterone system
      (RAAS) also attenuate oxidative stress, and improve endothelial, cardiac and
      renal functions, which collectively contribute to reductions in hypertension.

PMID- 22581416
TI  - Interpregnancy intervals and the risk for infant mortality: a case control study
      of Arizona infants 2003-2007.
AB  - There is well-documented evidence on how interpregnancy interval (IPI) is
      associated with adverse perinatal outcomes and how short and long IPIs are
      associated with increased risk for preterm birth, low birth weight, and intra
      uterine growth restriction. However, the extremes of IPI on infant mortality are
      less well documented. The current study builds on the existing evidence on IPI to
      examine if extremes of IPI are associated with infant mortality, and also
      examines if IPI is associated with both neonatal and post-neonatal mortality
      after adjusting for several known confounders. Matched birth and death
      certificate data for Arizona resident infants was drawn for 2003-2007 cohorts.
      The analysis was restricted to singleton births among resident mothers with a
      previous live birth (n = 1,466) and a randomly selected cohort of surviving
      infants during the same time-frame was used as a comparison group (n = 2,000).
      Logistic regression models were utilized to assess the odds for infant mortality
      at monthly interpregnancy intervals (<6, 6-11, 12-17, 18-23, 24-59, >=60), while
      adjusting for established predictors of infant mortality (i.e., preterm birth,
      low birth weight, and small for gestational age), and other potential
      confounders. Unadjusted analysis showed greater clustering at extreme IPIs of <6
      months and >=60 months for infants that died (32%) compared to infants that
      survived (24.7%). Shorter IPI (i.e., <6 months, 6-11 months, and 12-17 months)
      compared to 'ideal' IPI (i.e., 18-23 months), were associated with infant
      mortality even after adjusting for confounders. Short intervals were
      significantly associated with neonatal, but not post-neonatal deaths. IPI above
      23 months were not associated with infant mortality in our analyses. Shorter IPIs
      (18 months or less) significantly increases the risk for neonatal infant
      mortality even after controlling for known confounders, and our study adds to the
      existing evidence on adverse perinatal outcomes. Counseling women of reproductive
      age on the benefits of spacing pregnancies to at least 18 months addresses one
      preventable risk for early infant mortality.

PMID- 22581417
TI  - Colorectal Cancer in Pregnancy: Driven by Pregnancy-Associated Growth Factors?

PMID- 22581419
TI  - Giant hepatic hydatid cyst.

PMID- 22581418
TI  - Safety of bivalirudin in percutaneous coronary intervention following
      thrombolytic therapy.
AB  - OBJECTIVES: This study was undertaken to evaluate the safety of bivalirudin (BIV)
      use during percutaneous coronary intervention (PCI), following thrombolytic
      therapy in patients with ST-segment elevation myocardial infarction (STEMI).
      BACKGROUND: BIV has emerged as a safer anticoagulant than unfractionated heparin
      (UFH) during primary PCI; however, its use in patients who receive thrombolytic
      therapy has not been established. METHODS: A consecutive series of 104 patients
      who presented with STEMI treated with full-dose thrombolytics and who
      subsequently received PCI within 6 hr was identified and analyzed. BIV use was
      compared with UFH for in-hospital bleeding and ischemic events. The primary end
      points were the rate of major bleeding and the rate of net adverse clinical
      events as defined in the Harmonizing Outcomes with Revascularization and Stents
      in Acute Myocardial Infarction trial. The study cohort consisted of 104 patients,
      of whom 47 (45%) received BIV and 57 (55%) received UFH. RESULTS: Patients on BIV
      were more frequently preloaded with clopidogrel, while intraprocedural
      glycoprotein IIb/IIIa inhibitors were used only in UFH patients. In-hospital
      death, ischemic events, and thrombolysis in myocardial infarction major bleeding
      occurred more frequently in patients treated with UFH. The net adverse clinical
      events rate was lower in the intraprocedural BIV group (3 [6.4%] vs. 12 [21.1%]
      UFH, P = 0.034). CONCLUSIONS: The use of BIV in patients presenting with STEMI
      who were pretreated with thrombolytic therapy and who subsequently underwent PCI
      is safe and is associated with less ischemic and bleeding events when compared
      with UFH, and should be considered as the first line anticoagulant for these
      patients during PCI.

PMID- 22581420
TI  - Ambiguous genitalia: what prenatal genetic testing is practical?
AB  - Concern for ambiguous genitalia or chromosome-phenotype discordance detected in a
      prenatal setting has increased over the last two decades. Practitioners faced
      with this prenatal finding have a variety of genetic tests available to them;
      however, it is unclear to what extent prenatal testing for disorders of sex
      development (DSD) is useful or practical. We undertook a retrospective review of
      the medical records of 140 individuals evaluated through the DSD clinic at
      Seattle Children's Hospital with birthdates from 01/01/1994 through 08/16/2011 to
      determine the rate of prenatal detection of ambiguous genitalia in individuals
      with DSD, what prenatal diagnostic workup was undertaken, and the postnatal
      outcome, including whether a postnatal genetic diagnosis was confirmed. Of all
      140 subjects, 34 (24%) were identified prenatally. The most common postnatal
      diagnoses were penoscrotal hypospadias with transposition of the scrotum with no
      known genetic cause (24/140; 17%) and 21-hydroxylase deficiency (20/140; 14%).
      Apart from these, no single diagnosis comprised more than a few cases. Prenatal
      diagnostic testing varied widely, from no tests to multiple molecular tests with
      amniotic fluid hormone concentrations. In the absence of other fetal anomalies or
      growth retardation on ultrasound, prenatal karyotype with fluorescence in situ
      hybridization for the SRY gene is the most useful test when ambiguous genitalia
      is suspected. Further prenatal testing for Smith-Lemli-Opitz syndrome in 46,XY
      individuals and congenital adrenal hyperplasia in 46,XX individuals may be
      considered. However, targeted molecular testing for rare DSD conditions in the
      absence of a family history of DSD has a low yield.

PMID- 22581421
TI  - Glycemic control and survival in peritoneal dialysis patients with diabetes
      mellitus.
AB  - PURPOSE: The optimal target for glycated hemoglobin (HbA1c) has not been well
      defined in peritoneal dialysis (PD) patients with diabetes mellitus. METHODS: The
      objective of our study was to examine the predictive value of predialysis and
      time-averaged follow-up HbA1c values on technique and patient survival in
      diabetic PD patients treated in the Toronto General Hospital Home Peritoneal
      Dialysis Unit, between January 1, 2003 and December 31, 2008 with a median follow
      up period of 30+/-23 months. RESULTS: Ninety-one patients (mean age 64+/-13 years
      old) were included in this retrospective study. Patients were followed between 3
      and 91 months (mean duration 30+/-23 months). During this period, 40 patients
      died. We found no statistically significant correlation between baseline
      predialysis HbA1c values and technique and patient survival. Time-averaged follow
      up HbA1c in increments<6.5%, 6.5-8%, and >8% showed no significant survival
      difference among groups. CONCLUSIONS: There was no significant correlation of
      baseline and time-averaged follow-up HbA1c values with patient and PD technique
      survival.

PMID- 22581422
TI  - Electrocardiographic P-wave characteristics in patients with end-stage renal
      disease: P-index and interatrial block.
AB  - PURPOSE: P-wave parameters including P-wave dispersion (P d) have been examined
      in general population to predict development of atrial fibrillation (AF). But
      data on end-stage renal disease (ESRD) population are limited. P index (Pi) and
      interatrial block (IAB) as novel parameters may more accurately predict AF and
      have not been previously investigated in ESRD patients. We aimed to evaluate
      these novel ECG parameters in ESRD patients. METHODS: Eighty-six HD, 47 CAPD, and
      43 age- and gender-matched control subjects were enrolled in the study. P-wave
      duration was measured in all 12-leads of the surface ECG. The standard deviation
      of the P-wave duration across the 12 ECG leads was accepted as a Pi. P-wave
      duration above and equal to 110 ms was defined as IAB. All P-wave parameters were
      evaluated digitally by two observers. RESULTS: Pi was found to be significantly
      different among the groups in ANOVA. In post hoc analysis, P i was increased in
      HD group compared with the control group (p = 0.01). Also, P i tended to increase
      in CAPD group compared with controls (p = 0.06). The effect of ESRD on P i was
      independent of age, gender, and systolic blood pressure in univariate covariant
      analysis. The prevalence of IAB was 61, 55, and 32 % in patients with HD, CAPD,
      and controls, respectively (p = 0.001). P d was significantly higher in HD group
      compared with healthy controls. However, Pd values of CAPD patients did not show
      significant difference compared with controls. CONCLUSION: The present study
      demonstrated that IAB frequency and Pi were increased in patients with ESRD.

PMID- 22581423
TI  - Diagnostic utility of attenuation measurement (Hounsfield units) in computed
      tomography stonogram in predicting the radio-opacity of urinary calculi in plain
      abdominal radiographs.
AB  - OBJECTIVE: (1) To determine the best cut-off level of Hounsfield units (HU) in
      the CT stonogram that would predict the appearance of a urinary calculi in plain
      KUB X-ray; (2) to estimate the sensitivity and specificity of the best cut-off
      HU; and (3) to determine whether stone size and location affect the in vivo
      predictability. METHODS: A prospective cross-sectional study of patients aged 18
      85 diagnosed with urolithiases on CT stonogram with concurrent plain KUB
      radiograph was conducted. Appearance of stones was recorded, and significant
      difference between radiolucent and radio-opaque CT attenuation level was
      determined using ANOVA. Receiver operating characteristics (ROC) curve determined
      the best HU cut-off value. Stone size and location were used for factor
      variability analysis. RESULTS: A total of 184 cases were included in this study,
      and the average urolithiasis size on CT stonogram was 0.84 cm (0.3-4.9 cm). On
      KUB X-ray, 34.2 % of the urolithiases were radiolucent and 65.8 % were radio
      opaque. Mean value of CT Hounsfield unit for radiolucent stones was 358.25 (+/
      156), and that for radio-opaque stones was 816.51 (+/-274). ROC curve determined
      the best cut-off value of HU at 498.5, with the sensitivity of 89.3 % and
      specificity of 87.3 %. For >4 mm stones, the sensitivity was 91.3 % and the
      specificity was 81.8 %. On the other hand, for =<4 mm stones, the sensitivity was
      60 % and the specificity was 89.5 %. CONCLUSIONS: Based on the constructed ROC
      curve, a threshold value of 498.5 HU in CT stonogram was established as cut-off
      in determining whether a calculus is radio-opaque or radiolucent. The determined
      overall sensitivity and specificity of the set cut-off HU value are optimal.
      Stone size but not location affects the sensitivity and specificity.

PMID- 22581424
TI  - The effect of citrate replacement in hypocitraturic cases on the results of SWL:
      a preliminary prospective randomized study.
AB  - PURPOSE: To evaluate the possible effects of citrate replacement on the efficacy
      of shockwave lithotripsy (SWL) in the management of kidney stones in cases with
      hypocitraturia. METHODS: Forty hypocitraturic cases with renal pelvic stones were
      randomized into two groups; while citrate replacement has been done before and at
      the time of SWL in Study Group I (n: 20), SWL was performed without any
      additional specific management for hypocitraturia in Study Group II (n: 20).
      Twenty normocitraturic cases were also chosen as the control group (Group III).
      Data of the patients were evaluated comparatively. RESULTS: Patient, stone, and
      urinary pH characteristics of the groups were similar. Pre-SWL urinary citrate
      levels were 0.71 (0.1-1.3), 0.86 (0.1-1.4), and 3.12 (1.8-4.4) mmol/24 h in Group
      I, II, and III, respectively. Urinary citrate value increased from 0.71 (0.1-1.3)
      to 1.96 (1.6-4.1) mmol/24 h following replacement therapy (before and at the time
      of SWL) in Group I. Mean number of SW (p = 0.461), rate of stone-street formation
      (p = 0.146), and Double-J placement (p = 0.291) were similar in Group I and Group
      II. While the mean number of SWL sessions (2.27 +/- 0.71 in Group I vs. 2.94 +/-
      0.59 in Group II; p = 0.027), and time to stone-free status [29.1 (16-47) days in
      Group I vs. 38.4(21-63) days in Group II; p = 0.043], was significantly different
      between study groups, these parameters were found similar between Group I and
      Group III. CONCLUSIONS: In our study, the patients with hypocitraturia, who did
      receive replacement therapy, tended to require lower number of SWL sessions and
      became stone free in a shorter period than the others who underwent SWL without
      any specific management of hypocitraturia.

PMID- 22581425
TI  - Intrarenal pressures remain low with placement of a dual lumen catheter for
      retrograde irrigation to induce renal hypothermia.
AB  - OBJECTIVE: To determine whether placement of a 10 French dual lumen catheter
      produces a low-pressure collecting system during retrograde irrigation to induce
      renal hypothermia. Indication for the study is as a potential adjunct for partial
      nephrectomy. METHODS: Ex vivo porcine kidneys underwent harvest, and a ureteral
      catheter (either single lumen or dual lumen) was placed in the ureter within the
      renal pelvis. Pressure measurements (n = 1,080) were recorded at 1-s intervals.
      Irrigant flow rates were initiated at gravity and subsequently increased at 10
      cc/min increments to a maximum of 100 cc/min. RESULTS: During retrograde infusion
      without a dual lumen catheter, every 10 cc/min rate increase resulted in an 8 cm
      H(2)O rise in intrarenal pressure. The maximum flow rate obtained was 20 cc/min
      before urinary extravasation or intrarenal drainage occurred. Maximum pressure
      obtained before urinary extravasation or collecting system perforation was 16 cm
      H(2)O. Placement of a dual lumen catheter within the renal pelvis allowed
      intrarenal pressures to remain less than 5 cm H(2)O (when infusion rates <80
      cc/min). The maximum flow rate while maintaining pressures <20 cm H(2)O was 90
      cc/min. Flow rates above 100 cc/min resulted in urinary extravasation. The
      maximal flow rate that is safe for collecting systems with a dual lumen catheter
      is 80 cc/min, and without a dual lumen catheter rates greater than 20 cc/min
      resulted in collecting system perforations. CONCLUSION: Using an ex vivo porcine
      model, application of a 10 French ureteral dual lumen catheter produced adequate
      retrograde drainage that resulted in low intrarenal pressures at high infusion
      rates (up to 80 cc/min).

PMID- 22581426
TI  - Parechovirus infection preceding Guillain-Barre syndrome.

PMID- 22581427
TI  - Direct evidence that HSV DNA damaged by ultraviolet (UV) irradiation can be
      repaired in a cell type-dependent manner.
AB  - Infection of permissive cells, in tissue culture, with herpes simplex virus (HSV)
      has been reported to induce host DNA damage repair responses that are necessary
      for efficient viral replication. However, direct repair of the damaged viral DNA
      has not, to our knowledge, been shown. In this report, we detect and determine
      the amount of damaged HSV-1 DNA, following introduction of experimentally damaged
      HSV genomes into tissue cultures of permissive Vero, NGF differentiated PC12
      cells and primary rat neurons, using a method of detection introduced here. The
      results show that HSV-1 strain 17 DNA containing UV-induced DNA damage is
      efficiently repaired, in Vero, but not NGF differentiated PC12 cells. The primary
      rat neuronal cultures were capable of repairing the damaged viral DNA, but with
      much less efficiency than did the permissive Vero cells. Moreover, by conducting
      the experiments with either an inhibitor of the HSV polymerase (phosphonoacetic
      acid [PAA]) or with a replication defective DNA polymerase mutant virus, HP66,
      the results suggest that repair can occur in the absence of a functional viral
      polymerase, although polymerase function seems to enhance the efficiency of the
      repair, in a replication independent manner. The possible significance of varying
      cell type mediated repair of viral DNA to viral pathogenesis is discussed.

PMID- 22581429
TI  - Linking bacterial metabolism to graphite cathodes: electrochemical insights into
      the H(2) -producing capability of Desulfovibrio sp.
AB  - Microbial biocathodes allow converting and storing electricity produced from
      renewable sources in chemical fuels (e.g., H(2) ) and are, therefore, attracting
      considerable attention as alternative catalysts to more expensive and less
      available noble metals (notably Pt). Microbial biocathodes for H(2) production
      rely on the ability of hydrogenase-possessing microorganisms to catalyze proton
      reduction, with a solid electrode serving as direct electron donor. This study
      provides new chemical and electrochemical data on the bioelectrocatalytic
      activity of Desulfovibrio species. A combination of chronoamperometry, cyclic
      voltammetry, and impedance spectroscopy tests were used to assess the performance
      of the H(2) -producing microbial biocathode and to shed light on the involved
      electron transfer mechanisms. Cells attached onto a graphite electrode were found
      to catalyze H(2) production for cathode potentials more reducing than -900 mV vs.
      standard hydrogen electrode. The highest obtained H(2) production was 8 mmol L(
      1) per day, with a Coulombic efficiency close to 100 %. The electrochemical
      performance of the biocathode changed over time probably due to the occurrence of
      enzyme activation processes induced by extended electrode polarization.
      Remarkably, H(2) (at least up to 20 % v/v) was not found to significantly inhibit
      its own production.

PMID- 22581428
TI  - Specific protein profile in cerebrospinal fluid from HIV-1-positive cART-treated
      patients affected by neurological disorders.
AB  - Cytokines/chemokines are involved in the immune response of infections, including
      HIV-1. We defined the profile of 48 cytokines/chemokines in cerebrospinal fluid
      from 18 cART patients with chronic HIV-1 infection by Luminex technology. Nine
      patients were affected with leukoencephalopathies: five with John Cunningham
      virus (JCV) + progressive multifocal leukoencephalopathy (PML) and four with JCV
      not determined leukoencephalopathy (NDLE). In addition, nine HIV-1-positive
      patients with no neurological signs (NND) and five HIV-1-negative patients
      affected with acute disseminated encephalomyelitis (ADEM) were enrolled. Ten
      cytokines (IL-15, IL-3, IL-16, IL-18, CTACK, GRO1, SCF, MCP-1, MIF, SDF) were
      highly expressed in HIV-1-positive patients while IL-1Ra and IL-17 were present
      at a lower level. In addition, the levels of IL-17, IL-9, FGF-basic, MIP-1beta,
      and MCP-1 were significantly higher (p < 0.05) in patients with neurological
      diseases (PML, NDLE, ADEM) with respect to NND. Focusing the attention to the
      cytokine profile in JCV + PML patients with respect to JCV-NDLE patients, only
      TNF-beta was significantly downregulated (p < 0.05) in JCV + PML patients. This
      pilot study emphasized the role of immunoregulation in HIV-1-related neurological
      disorders during cART treatment.

PMID- 22581430
TI  - Preimplantation genetic diagnosis for chromosome rearrangements - one blastomere
      biopsy versus two blastomere biopsy.
AB  - PURPOSE: Preimplantation Genetic Diagnosis (PGD) has proven to be a useful
      reproductive option for carriers of some chromosome rearrangements. The data
      presented in this study compares the impact of one versus two blastomere biopsy
      on the likelihood of achieving a PGD result, as well as the effect on subsequent
      embryo development and clinical outcomes. METHODS: IVF-PGD couples had either one
      or two blastomeres biopsied from all embryos with >=7 blastomeres on day 3 post
      oocyte collection. These blastomeres were assessed for the specific chromosome
      rearrangement using Fluorescent In-situ Hybridisation (FISH). Further embryo
      development was monitored on days 4 and 5. Clinical outcomes were assessed
      retrospectively. RESULTS: The data shows that statistically more embryos achieved
      a PGD result following two blastomere biopsy, compared with one blastomere biopsy
      (92 % versus 88 %, respectively). Furthermore it was found that embryo
      development and clinical outcomes were similar between the two biopsy groups.
      CONCLUSIONS: Based on this analysis it appears that the biopsy of two blastomeres
      from embryos with >=7 blastomeres on day 3 is a valid and successful approach for
      couples presenting for IVF-PGD for a chromosome rearrangement.

PMID- 22581431
TI  - Chromosomal abnormalities in men with pregestational and gestational infertility
      in northeast China.
AB  - PURPOSE: To detect incidences and the types of chromosomal abnormalities in
      Chinese men with infertility and determine chromosomal factors association with
      various phenotypes. METHODS: Semen analysis and karyotype analysis by G-banding
      were carried out in 4,659 idiopathic infertile males; additionally, multiplex PCR
      using nine specific sequence-tagged sites (STSs) was used to detect azoospermia
      factor (AZF) microdeletions in 412 patients with Y chromosomal abnormalities.
      RESULTS: Male infertility was divided into pregestational infertility,
      characterized by failure to produce a fertilized ovum, and gestational
      infertility, characterized by embryo loss after fertilization. The former can
      result from azoospermia, oligozoospermia or oligoasthenozoospermia syndrome,
      while the latter is associated with developmental early pregnancy loss, habitual
      miscarriage and stillbirth. Among 4,659 male patients, 412 (8.84 %) showed
      abnormal chromosomal karyotypes, including 314 (6.74 %) with sex chromosomal
      abnormalities and 98 (2.10 %) with autosomal abnormalities. The prevalences of
      numerical and structural abnormalities among patients with chromosomal
      abnormalities were 259/412 (62.86 %) and 153/412 (37.14 %), respectively.
      Furthermore, structural sex chromosomal abnormalities were represented by various
      phenotypic profiles (46,XX, 47,XYY and 45,X/46,XY), and a prevalence of AZF
      microdeletions of 19/79 (24.05 %). AZF microdeletions were highly associated with
      Y chromosomal abnormalities (P = 0.018). CONCLUSION: Various chromosomal
      abnormalities that result in male infertility could affect spermatogenesis or
      embryonic development at different levels. Sex chromosomal and autosomal
      abnormalities were highly associated with pregestational and gestational
      infertility, respectively. AZF microdeletions may play an important role in
      lowering the stability of the Y chromosome.

PMID- 22581432
TI  - The beginnings of Acta Neurochirurgica and the work of Fritz Loew, chief editor
      from 1958 - 1997. An historical vignette.
AB  - Acta Neurochirurgica was founded in 1950, in the difficult time after World War
      II, by Mario Milletti (Bologna) and Wolfram Sorgo (Innsbruck), and published by
      Springer press, Vienna. From the beginning the new journal was conceived as an
      international journal with an impressive list of outstanding neurosurgeons in the
      editorial board. Only a few years later the issues appeared at irregular
      intervals due to individual problems of both editors. Wilhelm Tonnis took the
      initiative to keep the journal alive, when he asked-in consent with Springer
      press-his staff member Fritz Loew to continue the editorial work and to assemble
      a new prestigious editorial board. Loew succeeded with both tasks and remained
      editor-in-chief for nearly 38 years. Initially, all papers were published in the
      native languages of the authors: English, French, German, Italian and Spanish.
      With ongoing time the journal accepted manuscripts in English only. The slow
      progress of this process exemplifies the slow integration of the European
      countries. In 1971, at the founding meeting of the European Association of
      Neurosurgical Societies (EANS) in Prague, Acta Neurochirurgica became the
      official organ of the EANS. Right from the beginning of Acta Neurochirurgica,
      Supplement volumes were added. Also, the book series Advances and Technical
      Standards in Neurosurgery is an offspring of Acta Neurochirurgica. Acta
      Neurochirurgica has become one of the most important neurosurgical journals
      worldwide. This historical sketch is based on an interview with Fritz Loew, now
      91 years old, to which data from the available literature and the Archives of
      German Neurosurgery, as well as personal information by several colleagues were
      added.

PMID- 22581433
TI  - Neuropsychological outcome after extra-temporal epilepsy surgery.
AB  - BACKGROUND: The neuropsychological results of temporal lobe epilepsy surgery are
      well reported in the literature. The aim of this study was to analyse the
      neuropsychological outcome in a consecutive series of patients with extra
      temporal epilepsy. METHODS: We retrospectively analysed the data of patients
      operated between 1996 and 2008 for extra-temporal epilepsy. Standard
      neuropsychological tests were applied. We assessed the neuropsychological outcome
      after surgery and the correlation of the neuropsychological outcome with (1) side
      and localisation of surgery, (2) Engel scale for seizure outcome and (3) timing
      of surgery. FINDINGS: Patients had a better neuropsychological outcome when
      undergoing non-frontal resection [chi2 (2) =6.66, p = 0.036]. Subjects who had
      undergone left or right resection showed no difference in outcome [chi2 (2)
      =0.533, p = 0.766]. The correlation between the Engel scale for seizure re
      occurence and the neuropsychological scores showed only a tendency for better
      outcome (Spearman rho = -0.437; p = 0.069). The global measure of change did not
      correlate significantly with delay of surgery (Spearman rho = -0.163; p = 0.518).
      CONCLUSIONS: Resective epilepsy surgery improves neuropsychological status
      outcome in patients with extra-temporal epilepsy even if the patient did not
      become seizure free. The outcome is better for non-frontal localisation.

PMID- 22581434
TI  - Antihyperglycemic, hypolipidemic and antioxidant activities of ethanolic extract
      of Commiphora mukul gum resin in fructose-fed male Wistar rats.
AB  - High fructose feeding (66 % of fructose) induces type-2 diabetes in rats, which
      is associated with the insulin resistance, hyperinsulinemia, hypertriglyceridemia
      and oxidative stress. The present study was undertaken to evaluate the effect of
      ethanol extract of Commiphora mukul gum resin (CMEE) on blood glucose, plasma
      insulin, lipid profiles, reduced glutathione, lipid peroxidation, protein
      oxidation and enzymatic antioxidants like superoxide dismutase, catalase,
      glutathione reductase, glutathione peroxidase, glutathione-S-transferase in
      fructose-induced type-2 diabetic rats. A significant gain in body weight,
      hyperglycemia, hyperinsulinemia, increased lipid profiles, lipid peroxidation,
      protein oxidation and decreased reduced glutathione, activities of enzymatic
      antioxidants and insulin sensitivity (increased homeostasis assessment assay)
      were observed in high-fructose-induced diabetic rats. The administration of CMEE
      (200 mg/kg/day) daily for 60 days in high-fructose-induced diabetic rats reversed
      the above parameters significantly. CMEE has the ability to improve insulin
      sensitivity and delay the development of insulin resistance, aggravate
      antioxidant status in diabetic rats and may be used as an adjuvant therapy for
      patients with insulin resistance.

PMID- 22581435
TI  - Oleuropein prevents ethanol-induced gastric ulcers via elevation of antioxidant
      enzyme activities in rats.
AB  - Purified oleuropein from olive leaf extract has been shown to have antioxidant
      effects in our recent studies. Thus, the aim of this study was to assess the
      antioxidant abilities of oleuropein in comparison with ranitidine in ethanol
      induced gastric damages via evaluation of ulcer index inhibition, antioxidant
      enzyme activities, and lipid peroxidation level. Fifty-six adult male Sprague
      Dawley rats were divided into seven equal groups as follows: control group,
      ethanol group (absolute ethanol 1 ml/rat), oleuropein group (12 mg/kg), and
      oleuropein (6, 12, and 18 mg/kg) plus ethanol groups, as well as ranitidine (50
      mg/kg) plus ethanol group. Pretreatment with oleuropein (12 and 18 mg/kg)
      significantly increased the ulcer index inhibition (percent), in comparison with
      oleuropein (6 mg/kg). Glutathione peroxidase (GPx) activity was significantly
      lower in the ethanol group when compared with the other groups whereas, treatment
      of rats with oleuropein (12 mg/kg) significantly increased glutathione content in
      gastric tissue when compared with the other groups, and lipid peroxidation was
      significantly reduced in the oleuropein- (12 and 18 mg/kg) and ranitidine-treated
      animals. Superoxide dismutase (SOD) and catalase (CAT) activities were both much
      higher in oleuropein-treated rats than the ethanol group, and although there was
      a moderate increase in SOD and CAT activities in ranitidine-treated rats, the
      differences were not significant. These findings suggest that oleuropein has
      beneficial antioxidant properties against ethanol-induced gastric damages in the
      rat. Therefore, it seems that a combination regimen including both antioxidant
      and antisecretory drugs may be beneficial in prevention of ethanol-mediated
      gastric mucosal damages.

PMID- 22581436
TI  - PYK-2 is tyrosine phosphorylated after activation of pituitary adenylate cyclase
      activating polypeptide receptors in lung cancer cells.
AB  - The signal transduction mechanisms of pituitary adenylate cyclase activating
      polypeptide (PACAP) were investigated in lung cancer cells. Previously, PACAP-27
      addition to NCI-H838 cells increased phosphatidylinositol turnover and
      intracellular cAMP leading to proliferation of lung cancer cells. Also, PACAP
      receptors (PAC1) regulated the tyrosine phosphorylation of ERK, focal adhesion
      kinase, and paxillin. In this communication, the effects of PACAP on cytosolic
      Ca(2+) and PYK-2 tyrosine phosphorylation were investigated. PACAP-27 increased
      cytosolic Ca(2+) within seconds after addition to FURA-2 AM loaded NCI-H838
      cells. The increase in cytosolic Ca(2+) caused by PACAP was inhibited by PACAP(6
      38) (PAC1 antagonist), U73122 (phospholipase C inhibitor), or BAPTA (calcium
      chelator), but not H89 (PKA inhibitor). PACAP-38, but not vasoactive intestinal
      peptide (VIP), addition to NCI-H838 or H1299 cells significantly increased the
      tyrosine phosphorylation of PYK-2 after 2 min. The increase in PYK-2 tyrosine
      phosphorylation caused by PACAP was inhibited by PACAP(6-38), U73122, or BAPTA,
      but not H89. The results suggest that PAC1 regulates PYK-2 tyrosine
      phosphorylation in a calcium-dependent manner.

PMID- 22581437
TI  - Regulation by L-type calcium channels of endocytosis: an overview.
AB  - The exocytotic neurotransmitter release process is tightly coupled to the
      membrane retrieval (endocytosis) process since both are calcium-dependent
      processes. For instance, at the adrenal chromaffin cells, catecholamine release
      is regulated by Ca(2+) entry through L, N and PQ subtypes of voltage-dependent
      calcium channels (VDCC). The contribution of a given VDCC subtype to exocytosis
      may differ according to the animal species studied, with L channels contributing
      only about 20 % to the total Ca(2+) entry in bovine chromaffin cells. However,
      data from electrophysiological experiments with membrane capacitance measurements
      and fluorescence imaging with FM dyes indicate that Ca(2+) entry through the L
      type channels seems to selectively regulate the endocytotic response after the
      application of a single depolarizing pulse to voltage-clamped bovine chromaffin
      cells. How do L-type channels control endocytosis remains to be fully clarified.
      By using specific antibodies against VDCC subtypes and endocytic proteins (i.e.
      dynamin and clathrin), it has been demonstrated that VDCC subtypes do not co
      localise with these proteins. On the other hand, electrophysiological data
      suggest that the particular mode of sustained Ca(2+) entry through slow
      inactivating L-type channels could be responsible for the activation of the
      endocytotic machinery. Here, we present an overview of the current understanding
      of the contribution of L-type channels during endocytosis.

PMID- 22581438
TI  - Role of ROS/RhoA/PI3K/PKB signaling in NS1619-mediated blood-tumor barrier
      permeability increase.
AB  - The calcium-activated potassium channel (K (Ca) channel) activator, NS1619, has
      been shown to selectively and time-dependently increase the permeability of the
      blood-tumor barrier (BTB) by downregulating the expression of tight junction (TJ)
      protein. However, the role of signaling cascades in this process has not been
      precisely elucidated. This study was performed to determine the role of signaling
      cascades involving reactive oxygen species (ROS)/RhoA/PI3K/PKB in increasing the
      permeability of the BTB induced by NS1619. Using an in vitro BTB model and
      selective inhibitors of signaling pathways, we investigated whether
      ROS/RhoA/PI3K/PKB pathway plays a key role in the process of the increase in BTB
      permeability induced by NS1619. The results revealed that the BTB permeability
      was increased and the expression of TJ proteins were significantly decreased by
      NS1619, and selective inhibitors of identified signaling pathways reversed the
      observed alterations. Moreover, the significant increases in ROS, RhoA activity,
      and PKB phosphorylation after NS1619 administration were observed, which were
      partly inhibited by N-2-mercaptopropionyl glycine or C3 exoenzyme or LY294002
      pretreatment. The present study demonstrates that the activation of signaling
      cascades involving ROS/RhoA/PI3K/PKB in rat brain microvascular endothelial cells
      was required for the increase in BTB permeability induced by NS1619.

PMID- 22581440
TI  - Retracted article: miR-598 induces replicative senescence in human adipose tissue
      derived mesenchymal stem cells via silent information regulator 1.

PMID- 22581439
TI  - Immunohistochemical distribution of somatostatin and somatostatin receptor
      subtypes (SSTR1-5) in hypothalamus of ApoD knockout mice brain.
AB  - In the present study, the expression of somatostatin (SST) and somatostatin
      receptor subtypes (SSTR1-5) was determined in the hypothalamus of wild-type (wt)
      and apolipoprotein D knockout (ApoD(-/-)) mice brain. SST-like immunoreactivity,
      while comparable in most regions of hypothalamus, diminished significantly in
      arcuate nucleus of ApoD(-/-) mice. SSTR1 strongly localized in all major
      hypothalamic nuclei as well as in the median eminence and ependyma of the third
      ventricle of wt mice brain. SSTR1-like immunoreactivity increases in hypothalamus
      except in paraventricular nucleus of ApoD(-/-) mice. SSTR2 was well expressed in
      most of the hypothalamic regions whereas it decreases significantly in
      ventromedial and arcuate nucleus of ApoD(-/-) mice. SSTR3 and SSTR4-like
      immunoreactivity increases in ApoD(-/-) mice in all major nuclei of hypothalamus,
      median eminence, and ependymal cells of third ventricle. SSTR5 is well expressed
      in ventromedial and arcuate nucleus whereas weakly expressed in paraventricular
      nucleus. In comparison to wt, ApoD(-/-) mice exhibit increased SSTR5-like
      immunoreactivity in paraventricular nuclei and decreased receptor expression in
      ventromedial hypothalamus and arcuate nucleus. In conclusion, the changes in
      hypothalamus of ApoD(-/-) mice may indicate potential role of ApoD in regulation
      of endocrine functions of somatostatin in a receptor-dependent manner.

PMID- 22581441
TI  - Twist expression associated with the epithelial-mesenchymal transition in gastric
      cancer.
AB  - This study aimed to investigate the expression of Twist in gastric cancer tissues
      and its correlation between Twist and the epithelial-mesenchymal transition
      (EMT). By means of RT-PCR and Western blot, the mRNA and protein expressions of
      Twist, E-cadherin, and Vimentin in 61 gastric cancer tissues and adjacent normal
      tissues were detected. The positive rates of Twist, E-cadherin, and Vimentin mRNA
      expression in gastric cancer tissues were 73.9. 40.6, and 60.9 %, respectively;
      compared to the expression of these genes in adjacent normal tissues (2.9, 75.4,
      and 27.5 %), the differences were significant (p < 0.05). The E-cadherin protein
      expression level in gastric cancer tissues was significantly lower than that in
      the adjacent normal tissues (p < 0.05). After the transfection of Twist siRNA
      into the MKN45 cells, the protein expression of Twist was significantly reduced
      (p < 0.05), the protein expression of E-cadherin was significantly increased, and
      the number of cells that passed through the Transwell chamber was significantly
      lower than that in the non-transfected control group as well as the transfected
      control group (p < 0.05). Twist may be associated with the epithelial-mesenchymal
      transition in gastric cancer and the tumorigenesis, invasion, and metastasis of
      gastric cancer.

PMID- 22581442
TI  - Esculetin promotes type I procollagen expression in human dermal fibroblasts
      through MAPK and PI3K/Akt pathways.
AB  - Type I collagen is the major constituent of the skin and the reduction of dermal
      type I collagen content is closely associated with the intrinsic skin aging. We
      here found that esculetin, 6,7-dihydroxycoumarin, strongly induces type I
      procollagen expression in human dermal fibroblasts. Esculetin not only increased
      protein levels of type I procollagen but also increased mRNA levels of COL1A1 but
      not COL1A2. Esculetin activated the MAPKs (ERK1/2, p38, JNK) and PI3K/Akt
      pathways, through which it promoted the type I procollagen expression. We also
      demonstrated that the binding motifs for transcription factor Sp1 occur with the
      highest frequency in the COL1A1 promoter and that esculetin increases the Sp1
      expression through the MAPK and PI3K/Akt pathways. These results suggest that
      esculetin promotes type I procollagen expression through the MAPK and PI3K/Akt
      pathways and that Sp1 might be involved in the esculetin-induced type I
      procollagen expression via activation of the COL1A1 transcription.

PMID- 22581443
TI  - Evaluation of a mobile NMR sensor for determining skin layers and locally
      estimating the T(2eff) relaxation time in the lower arm.
AB  - OBJECT: The nuclear magnetic resonance (NMR) mobile-universal-surface-explorer
      (MOUSE) was evaluated in a pilot study to determine its ability to detect
      physiological changes in human skin caused by physical or pharmacological
      interventions. MATERIALS AND METHODS: The left lower arm skin thicknesses of ten
      male subjects were measured five times using a Profile NMR-MOUSE((r)) ((1)H, 19
      MHz) before and after a venous occlusion manoeuvre. In five of the subjects, the
      T(2eff) relaxation times were derived from a bi-exponential fitting and were
      determined in the dermis and subcutis before and after applying a salve
      containing capsaicin. RESULTS: The dermis (including the epidermis) showed rather
      homogeneous signal amplitudes. The subcutis was characterised by higher and more
      variable amplitudes. The full-skin thickness values were affirmed by ultrasound
      imaging. The NMR profiles did not show significant skin swelling due to venous
      occlusion. In the dermis, capsaicin caused significant (p < 0.05) decreases in
      both components of T(2eff) (100 +/- 19 ms-19 +/- 10 ms; 9.5 +/- 0.5 ms-7.2 +/-
      1.6 ms). In the subcutis, the T(2eff) was not affected. CONCLUSION: In principle,
      NMR-MOUSE profiles are capable of detecting skin structure. However, precise
      measurements are jeopardised by poor reproducibility, long acquisition times, and
      incompatibility between the geometries of the sensitive area of the instrument
      and the non-planar structure of the skin. In the dermis, T(2eff) contrast could
      be used to detect the changes in tissue composition caused by inflammatory
      reactions.

PMID- 22581444
TI  - Identification and genomic analysis of two duck-origin Tembusu virus strains in
      southern China.
AB  - Egg-laying duck flocks in Guangdong province, southern China, have been suffering
      a widely spreading infectious disease with abrupt egg drops and death since the
      winter of 2010. However, the causative pathogen was not known. We obtained two
      independent virus isolates named FS and JM from the diseased layer duck flocks
      and identified them as duck-origin Tembusu virus by PCR detection, sequencing the
      entire length of the open reading frames (ORFs). The two isolates FS and JM
      shared high sequence similarity to the isolates of duck-origin Tembusu virus that
      was first emerged in eastern China in April 2010. Blast analysis shows that the
      whole ORF sequences of FS and JM have the highest similarity (>99 %) to BYD-1(the
      first reported duck-origin Tembusu virus) and JS804 (the first reported goose
      origin Tembusu virus), indicating that the full-length genomes were highly
      conserved in waterfowl-origin Tembusu viruses. The present study suggests that
      duck-origin Tembusu viruses have spread fast from eastern China to southern
      China, causing widely spreading infections. The high conservation of duck-origin
      Tembusu virus strains provides the genomic basis for choosing the strains for
      vaccine preparation for better protection against this new virus infection.

PMID- 22581445
TI  - Helicoverpa armaigera nucleopolyhedrovirus ORF50 is an early gene not essential
      for virus propagation in vitro and in vivo.
AB  - Homologs of Helicoverpa armigera nucleopolyhedrovirus ORF50 (HA50) are found in
      most alphabaculoviruses, but their functions remain unknown. Here, we
      characterized whether Ha50 is indispensable for virus progration. Ha50 transcript
      was first detected at 3 h post-infection from HearNPV-infected HzAM1 cells.
      3'RACE analysis showed that Ha50 transcript was polyadenlylated. 5'RACE analysis
      revealed two transcription initiation sites, one of which was mapped to the
      canonical baculovirus early transcription initiator motif CAGT. HA50 protein
      could be detected from infected cells harvested at 12 h post-infection. Transient
      expression assays showed that GFP-fused HA50 localized in the cytoplasm and
      nucleus of HzAM1 cells with or without superinfection. To further examine the
      role of Ha50 in the virus life cycle, a Ha50 knockout bacmid and a repair bacmid
      carrying Ha50 under the control of its native promoter elements were constructed
      using bacmid technology. One-step growth curve analysis showed that the kinetics
      of infectious budded virus production of Ha50 knockout virus was similar to that
      of the parental virus or the repair virus. Analysis of the expression of viral
      early protein IE-1, late protein VP39 and very late protein suggested that viral
      protein expression was not affected by Ha50 inactivation. Electron microscopy
      revealed that HaBacDelta50-PH-G occluded viruses (ODVs) and occlusion bodies were
      indistinguishable from those of the wild-type virus. Similarly, bioassays showed
      no significant difference in the LC(50) values between Ha50 deletion virus and
      wild-type virus. Our results together demonstrate that Ha50 is an early gene
      dispensable for virus propagation in vitro and in vivo.

PMID- 22581446
TI  - Genomic aberrations relate early and advanced stage ovarian cancer.
AB  - BACKGROUND: Because of the distinct clinical presentation of early and advanced
      stage ovarian cancer, we aim to clarify whether these disease entities are solely
      separated by time of diagnosis or whether they arise from distinct molecular
      events. METHODS: Sixteen early and sixteen advanced stage ovarian carcinomas,
      matched for histological subtype and differentiation grade, were included.
      Genomic aberrations were compared for each early and advanced stage ovarian
      cancer by array comparative genomic hybridization. To study how the aberrations
      correlate to the clinical characteristics of the tumors we clustered tumors based
      on the genomic aberrations. RESULTS: The genomic aberration patterns in advanced
      stage cancer equalled those in early stage, but were more frequent in advanced
      stage (p = 0.012). Unsupervised clustering based on genomic aberrations yielded
      two clusters that significantly discriminated early from advanced stage (p =
      0.001), and that did differ significantly in survival (p = 0.002). These clusters
      however did give a more accurate prognosis than histological subtype or
      differentiation grade. CONCLUSION: This study indicates that advanced stage
      ovarian cancer either progresses from early stage or from a common precursor
      lesion but that they do not arise from distinct carcinogenic molecular events.
      Furthermore, we show that array comparative genomic hybridization has the
      potential to identify clinically distinct patients.

PMID- 22581447
TI  - Inherited thrombophilia in children with venous thromboembolism and the familial
      risk of thromboembolism: an observational study.
AB  - Screening for inherited thrombophilia (IT) is controversial; persons at high risk
      for venous thromboembolism (VTE) who benefit from screening need to be
      identified. We tested 533 first- and second-degree relatives of 206 pediatric VTE
      patients for IT (antithrombin, protein C, protein S, factor V G1691A, factor II
      G20210A) and determined the incidence of symptomatic VTE relative to their IT
      status. The risk for VTE was significantly increased among family members with,
      versus without, IT (hazard ratio = 7.6; 95% confidence interval [CI], 4.0-14.5; P
      < .001) and highest among carriers of antithrombin, protein C, or protein S
      deficiency (hazard ratio = 25.7; 95% CI, 12.2-54.2; P < .001). Annual incidences
      of VTE were 2.82% (95% CI, 1.63%-4.80%) among family members found to be carriers
      of antithrombin, protein C, or protein S deficiency, 0.42% (0.12%-0.53%) for
      factor II G202010A, 0.25% (0.12%-0.53%) for factor V G1691A, and 0.10% (0.06%
      0.17%) in relatives with no IT. Given the high absolute risk of VTE in relatives
      with protein C, protein S, and antithrombin deficiency, we suggest screening for
      these forms of hereditary thrombophilia in children with VTE and their relatives.
      Interventional studies are required to assess whether thromboembolism can be
      prevented in this high-risk population.

PMID- 22581448
TI  - Targeting antiapoptotic A1/Bfl-1 by in vivo RNAi reveals multiple roles in
      leukocyte development in mice.
AB  - Gene-targeting studies in mice have identified the essential roles of most
      prosurvival Bcl-2 family members in normal physiology and under conditions of
      stress. The function of one member, Bcl2a1/Bfl-1/A1, is only poorly understood
      because of quadruplication of its gene locus in mice, hindering conventional
      knockout studies. To overcome this problem, we generated mouse models allowing
      traceable constitutive or reversible ablation of A1 in the hematopoietic system
      by RNA interference. Knockdown of A1 impaired early stages of T-cell
      differentiation, B-cell homeostasis, and sensitized transitional as well as
      follicular B cells to apoptosis induced by ligation of the B-cell receptor. As a
      consequence, B-cell proliferation in response to mitogens was severely impaired,
      whereas that of T cells appeared unaffected. Furthermore, depending on the extent
      of A1 knockdown, granulocytes showed increased spontaneous death in culture or
      failed to accumulate in significant numbers in vivo. These models highlight the
      critical role of A1 in leukocyte development and homeostasis, constituting
      valuable tools for investigating presumed roles of this Bcl-2 family member in
      immunity, tumorigenesis, and drug resistance.

PMID- 22581451
TI  - Prediction of free energies of hydration with COSMO-RS on the SAMPL3 data set.
AB  - The COSMO-RS method has been used for the prediction of free energies of
      hydration on the dataset of 36 chlorinated ethanes, biphenyls and dioxins
      considered in the SAMPL3 challenge. Straight application of the latest version of
      the COSMOtherm software yields an overall predictive accuracy of 1.05 kcal/mol
      (RMSE). The predictions for the chlorinated ethanes and dioxins are much better
      with 0.40 and 0.49 kcal/mol RMSE, respectively. The predictions for the
      chlorinated biphenyls show a systematic shift of approximately 1 kcal/mol, but
      the large RMSE of 1.59 kcal/mol mainly arises from two exceptional outliers.
      Possible reasons for this observation are discussed.

PMID- 22581450
TI  - Differential BDNF responses of triple versus dual reuptake inhibition in neuronal
      and astrocytoma cells as well as in rat hippocampus and prefrontal cortex.
AB  - Monoamine reuptake inhibitors increase brain-derived neurotrophic factor (BDNF)
      activity, and this growth factor is regarded as an interesting target for
      developing new antidepressant drugs. The aims of this study were to evaluate
      whether monoaminergic reuptake inhibition increases BDNF in vivo and in vitro as
      predicted by the neurotrophic hypothesis of depression, and whether triple
      reuptake inhibition has a superior BDNF response compared to dual reuptake
      inhibition. Twenty-one days of oral treatment (30 mg/kg) with the dual
      serotonin/noradrenaline reuptake inhibitor duloxetine or the triple
      serotonin/noradrenaline/dopamine reuptake inhibitor DOV 216,303 restored BDNF
      protein levels in the rat hippocampus, which were initially decreased due to
      injection stress. The prefrontal cortex contained increased BDNF levels only
      after DOV 216,303 treatment. In vitro, neither duloxetine nor DOV 216,303 altered
      intracellular BDNF levels in murine HT22 neuronal cells. In contrast, BDNF
      release was more effectively decreased following treatment with DOV 216,303 in
      these cells. In rat C62B astrocytomas, both antidepressants increased
      intracellular BDNF levels at their highest nontoxic concentration. C62B
      astrocytomas did not release BDNF, even after antidepressant treatment. Increased
      BDNF levels support the neurotrophic hypothesis of depression, but our findings
      do not clearly evidence that the BDNF response after triple reuptake inhibitors
      is more effective than after dual reuptake inhibitors. Moreover, the data suggest
      that the role of BDNF in neurons and astrocytes is complex and likely depends on
      factors including specificity of cell types in different brain regions, cell-cell
      interactions, and different mechanisms of action of antidepressants used.

PMID- 22581452
TI  - A mathematical model of utility for single screening of asymptomatic unruptured
      intracranial aneurysms at the age of 50 years.
AB  - BACKGROUND: Although rupture of intracranial aneurysms carries high mortality and
      morbidity rates, the clinical and financial benefit of screening certain high
      risk groups is uncertain. We designed a mathematical model to interrogate the
      clinical benefit and cost-effectiveness of screening. METHODS: A decision tree
      analysis model was used to calculate the outcome and cost of two scenarios
      applied to the same population: one-off screening for intracranial aneurysms
      versus not screening. Each scenario had an associated gain or loss of Quality
      Adjusted Life Years (QALY) and cost; the difference between the two scenarios was
      calculated. The variable inputs were the aneurysm prevalence and risk of rupture
      after 5 years. Sensitivity analyses were performed to determine the effects of
      altering various factors on outcomes. RESULTS: Screening of the asymptomatic
      general population results in a QALY loss, equating to a negative clinical
      impact. The threshold 5-year risk of rupture at which screening resulted in a
      gain in QALYs was 13 %. This held true for any prevalence between 1 and 25 %.
      Risk of rupture had a greater impact on outcome than prevalence. Halving the risk
      of intervention (either surgery or coiling) reduced the threshold 5-year risk of
      rupture at which screening results in gain of QALYs to 6 %. The age of screening
      also had important effects on outcome. CONCLUSIONS: The QALY benefit and cost
      effectiveness of screening are most sensitive to the 5-year risk of rupture.
      Screening is beneficial only in populations with a high risk of rupture; this
      should be the focus of future research.

PMID- 22581449
TI  - Role of neurotrophins in the development and function of neural circuits that
      regulate energy homeostasis.
AB  - Members of the neurotrophin family, including nerve growth factor, brain-derived
      neurotrophic factor, neurotrophin-3, and neurotrophin-4/5, and other neurotrophic
      growth factors such as ciliary neurotrophic factor and artemin, regulate
      peripheral and central nervous system development and function. A subset of the
      neurotrophin-dependent pathways in the hypothalamus, brainstem, and spinal cord,
      and those that project via the sympathetic nervous system to peripheral metabolic
      tissues including brown and white adipose tissue, muscle and liver, regulate
      feeding, energy storage, and energy expenditure. We briefly review the role that
      neurotrophic growth factors play in energy balance, as regulators of neuronal
      survival and differentiation, neurogenesis, and circuit formation and function,
      and as inducers of critical gene products that control energy homeostasis.

PMID- 22581453
TI  - 17-Alpha-estradiol ameliorating oxygen-induced retinopathy in a murine model.
AB  - PURPOSE: Our aim was to explore the effects and mechanism of 17-alpha-estradiol
      (17alpha-E2) on oxygen-induced retinopathy (OIR) in a murine model. METHODS:
      Newborn mice exposed to hyperoxia underwent subcutaneous injections of different
      doses of 17alpha-E2 from postnatal days (PND) 7 to 17. The retinal flat mounts
      were scored for avascular/total retinal area on PND 17. Vascular endothelial
      growth factor (VEGF), malondialdehyde (MDA) concentrations, and intensity,
      activity, and quality of reduced nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase in the retina were determined on PND 9, 13 (14), and 17. RESULTS:
      The avascular area, which is found in retinas of hyperoxia-exposed pups but not
      in retinas of normoxia-exposed ones, was significantly smaller in retinas of
      17alpha-E2-treated pups. MDA and VEGF concentrations and intensity, activity, and
      quality of NADPH oxidase were stable in retinas of normoxia pups on PND 9, 13
      (14), and 17, whereas in retinas of hyperoxia-exposed and 17alpha-E2-treated
      pups, they fluctuated markedly. VEGF concentrations were lower in retinas of
      hyperoxia-exposed pups than in those of normoxia ones on PND 9. Elevated VEGF
      concentrations were found in retinas of 17alpha-E2-treated pups on PND 9 and in
      hyperoxia-exposed pups on PND 14 and 17. Low VEGF concentrations were found in
      retinas of 17alpha-E2-treated pups on PND 14 and 17. MDA concentrations and NADPH
      oxidase concentration and activity, which were higher in retinas of hyperoxia
      exposed pups, were lower in retinas of 17alpha-E2-treated pups on PND 9, 13, and
      17. The most effective outcome in retinas of 1.0 MUg 17alpha-E2-treated pups was
      markedly reversed by ICI182780. CONCLUSIONS: We found that 17alpha-E2 mitigates
      oxidative stress reactions and ameliorates OIR severity by decreasing NADPH
      oxidase expression and activity via the receptor and other pathways.

PMID- 22581454
TI  - Efficacy and safety of switching to travoprost/timolol fixed-combination therapy
      from latanoprost monotherapy.
AB  - PURPOSE: To prospectively assess the efficacy of switching to a
      travoprost/timolol fixed-combination (TTFC) therapy from latanoprost monotherapy.
      METHODS: This was a prospective, open-label study in which patients with either
      primary open-angle glaucoma or ocular hypertension who had been undergoing
      latanoprost monotherapy for at least 3 months were enrolled. Baseline was defined
      as the time when the subjects were started on latanoprost monotherapy.
      Examination periods were defined as 1, 2, and 3 months the switch to TTFC
      therapy, and 1-2 months after the switch back to latanoprost monotherapy. The
      parameters examined were intraocular pressure (IOP), conjunctival hyperemia, and
      corneal erosion, as well as blood pressure and heart rate. A survey was conducted
      1 and 3 months after the switch to TTFC therapy with a focus on each subject's
      impressions. RESULTS: Among the 70 enrolled subjects, the 58 (29 men, 29 women)
      who completed the protocol were analyzed. The IOP before and at 1, 2, and 3
      months after the switch to TTFC therapy was measured and again after the switch
      back to latanoprost monotherapy. The results indicated that TTFC therapy
      significantly reduced the IOP (P < 0.001) and significantly decreased the heart
      rate, but it did not significantly change either the systolic or diastolic blood
      pressure. TTFC therapy also did not significantly change either the conjunctival
      hyperemia or corneal erosion. In the questionnaire, the patients indicated that
      their impression was that there was no significant difference between the two
      ophthalmic solutions. CONCLUSIONS: Compared to latanoprost monotherapy, TTFC
      therapy significantly reduced IOP and decreased the heart rate in the patient
      cohort. No differences were found in terms of patients' impressions.

PMID- 22581457
TI  - Differential abilities of chicken Pit1 isoforms to regulate the GH promoter:
      evidence for synergistic activation.
AB  - Pit1, pituitary-specific transcription factor 1, regulates differentiation of
      cells of the Pit1 lineage in the anterior pituitary and the synthesis of peptide
      hormones by these cell types, including GH. Pit1 is characterized by an N
      terminal transactivation domain and a C-terminal POU domain. Alternative forms of
      Pit1, differing from each other in the N-terminal domain, have been reported in
      several species, but the functional implication of having multiple isoforms is
      not known. Several PIT1 mRNA transcripts exist in chickens that have not been
      characterized. This study was conducted to determine which, if any, of the
      chicken Pit1 isoforms regulate the chicken GH (cGH) promoter. During the course
      of this work, Pit1beta2, a novel isoform of chicken Pit1, was discovered. Effects
      of known and novel isoforms (Pit1alpha, Pit1beta1, Pit1beta2, and Pit1gamma) on
      cGH promoter activity were characterized in chicken Leghorn male hepatoma cells.
      Three of the isoforms, Pit1alpha, Pit1beta1, and Pit1beta2, activated the cGH
      promoter, whereas Pit1gamma did not. Results from gel-shift assays indicated that
      Pit1gamma does not bind to the proximal Pit1-bindng site of the cGH promoter,
      suggesting a possible mechanism underlying its inactivity. We found a functional
      advantage for having multiple isoforms expressed. When Pit1beta1 was coexpressed
      with Pit1alpha or Pit1beta2, significantly greater activation of the cGH promoter
      occurred than with any one isoform alone, with synergistic activation occurring
      when Pit1alpha and Pit1beta1 were coexpressed. Whether this increased activation
      required, or was facilitated by, heterodimerization of two isoforms is not known.
      Identification of isoforms with specific functions will facilitate identification
      of their respective interacting partners that are essential for GH gene
      expression.

PMID- 22581458
TI  - Inhibitor of G protein-coupled receptor kinase 2 normalizes vascular endothelial
      function in type 2 diabetic mice by improving beta-arrestin 2 translocation and
      ameliorating Akt/eNOS signal dysfunction.
AB  - In type 2 diabetes, although Akt/endothelial NO synthase (eNOS) activation is
      known to be negatively regulated by G protein-coupled receptor kinase 2 (GRK2),
      it is unclear whether the GRK2 inhibitor would have therapeutic effects. Here we
      examined the hypotensive effect of the GRK2 inhibitor and its efficacy agonist
      both vascular (aortic) endothelial dysfunction (focusing especially on the
      Akt/eNOS pathway) and glucose intolerance in two type 2 diabetic models (ob/ob
      mice and nicotinamide+streptozotocin-induced diabetic mice). Mice were treated
      with a single injection of the GRK2 inhibitor or vehicle, and the therapeutic
      effects were compared by examining vascular function and by Western blotting. The
      GRK2 inhibitor lowered blood pressure in both diabetic models but not in their
      age-matched controls. The GRK2 inhibitor significantly improved clonidine-induced
      relaxation only in diabetic (ob/ob and DM) mice, with accompanying attenuations
      of GRK2 activity and translocation to the plasma membrane. These protective
      effects of the GRK2 inhibitor may be attributable to the augmented Akt/eNOS
      pathway activation (as evidenced by increases in Akt phosphorylation at Ser(473)
      and at Thr(308), and eNOS phosphorylation at Ser(1177)) and to the prevention of
      the GRK2 translocation and promotion of beta-arrestin 2 translocation to the
      membrane under clonidine stimulation. Moreover, the GRK2 inhibitor significantly
      improved the glucose intolerance seen in the ob/ob mice. Our work provides the
      first evidence that in diabetes, the GRK2 inhibitor ameliorates vascular
      endothelial dysfunction via the Akt/eNOS pathway by inhibiting GRK2 activity and
      enhancing beta-arrestin 2 translocation under clonidine stimulation, thereby
      contributing to a blood pressure-lowering effect. We propose that the GRK2
      inhibitor may be a promising therapeutic agent for cardiovascular complications
      in type 2 diabetes.

PMID- 22581459
TI  - Inactivation of AMPKalpha1 induces asthenozoospermia and alters spermatozoa
      morphology.
AB  - AMP-activated protein kinase (AMPK), a key regulator of cellular energy
      homeostasis, is present in metabolic tissues (muscle and liver) and has been
      identified as a modulator of the female reproductive functions. However, its
      function in the testis has not yet been clearly defined. We have investigated the
      potential role of AMPK in male reproduction by using transgenic mice lacking the
      activity of AMPK catalytic subunit alpha1 gene [alpha1AMPK knockout (KO)]. In the
      testis, the alpha1AMPK subunit is expressed in germ cells and also in somatic
      cells (Sertoli and Leydig cells). alpha1AMPK KO male mice show a decrease in
      fertility, despite no clear alteration in the testis morphology or sperm
      production. However, in alpha1AMPK(-/-) mice, we demonstrate that spermatozoa
      have structural abnormalities and are less motile than in control mice. These
      spermatozoa alterations are associated with a 50% decrease in mitochondrial
      activity, a 60% decrease in basal oxygen consumption, and morphological defects.
      The alpha1AMPK KO male mice had high androgen levels associated with a 5- and 3
      fold increase in intratesticular cholesterol and testosterone concentrations,
      respectively. High concentrations of proteins involved in steroid production
      (3beta-hydroxysteroid dehydrogenase, cytochrome steroid 17 alpha
      hydroxylase/17,20 lysate, and steroidogenic acute regulatory protein) were also
      detected in alpha1AMPK(-/-) testes. In the pituitary, the LH and FSH
      concentrations tended to be lower in alpha1AMPK(-/-) male mice, probably due to
      the negative feedback of the high testosterone levels. These results suggest that
      total alpha1AMPK deficiency in male mice affects androgen production and quality
      of spermatozoa, leading to a decrease in fertility.

PMID- 22581460
TI  - Worsened outcome from middle cerebral artery occlusion in aged rats receiving
      17beta-estradiol.
AB  - Although estrogens are neuroprotective in young adult animal models of stroke,
      clinical trials demonstrate that estrogens increase the incidence and severity of
      stroke in aged women. We have previously shown that experimental stroke
      pathophysiology differs between young adult and aged rats. The aim of this study
      was to determine the effects of 17beta-estradiol after middle cerebral artery
      occlusion and reperfusion in young adult and aged female rats. Focal embolic
      stroke was performed by middle cerebral artery occlusion with fibrin clot
      followed by reperfusion with i.v. human recombinant tissue plasminogen activator.
      Histological and functional outcomes were measured at 24 h after middle cerebral
      artery occlusion with fibrin clot. Aged rats treated with 17beta-estradiol had
      significantly increased infarct volumes compared with placebo-treated aged rats.
      Young adult rats treated with 17beta-estradiol had significantly decreased
      infarct volumes and improved functional outcome compared with ovariectomized
      young adult rats. Our results suggest that 17beta-estradiol may act in an age
      dependent manner in the postischemic rat brain. In young adult rats, it is
      neuroprotective; chronic treatment with 17beta-estradiol during aging leads to
      worsened ischemic brain injury in aged female rats.

PMID- 22581461
TI  - Genotypic intraspecies heterogeneity of Enterococcus italicus: data from dairy
      environments.
AB  - The diversity of a collection of 19 Enterococcus italicus strains isolated from
      different dairy sources was explored using a molecular polyphasic approach,
      comprising random amplification of polymorphic DNA (RAPD-PCR), repetitive element
      PCR (REP-PCR), plasmid profiling and ribotyping. The data obtained showed a high
      level of biodiversity, not always correlated to the niche of isolation.
      Particularly, REP-PCR with primer BOXA1R and plasmid profiling allowed the best
      discrimination at strain level. Exploiting the genome shotgun sequence of the
      type strain of the species, available in public database, genes related to
      insertion sequences present on enterococcal Pathogenic Islands (ISEf1, IS905),
      determinants related to virulence factors (codifying for hemolysin and cell wall
      surface proteins), exogenously DNA (conjugal transfer protein, replication
      plasmid protein, pheromone shutdown protein, phage integrase/recombinase) and
      penicillin binding proteins system were detected. The presence of most of these
      genes seemed a common genetic trait in the Enterococcus genus, sur gene (cell
      wall surface protein) was only detected in strains of E. italicus. To our
      knowledge, this is the first time that specific primers, with the expection of
      the species-specific probe targeted to 16S rRNA gene, have been designed for this
      species.

PMID- 22581462
TI  - [Cu(dap)2Cl] as an efficient visible-light-driven photoredox catalyst in carbon
      carbon bond-forming reactions.
AB  - Copper sees the light of day: [Cu(dap)(2)Cl] proved to be an excellent photoredox
      catalyst for atom-transfer radical addition reactions, as well as for allylation
      reactions (see scheme), providing an attractive alternative to commonly used
      iridium- and ruthenium-based catalysts.

PMID- 22581463
TI  - Switching antiplatelet regimens: alternatives to clopidogrel in patients with
      acute coronary syndrome undergoing PCI: a review of the literature and practical
      considerations for the interventional cardiologist.
AB  - Dual antiplatelet therapy with aspirin plus a P2Y(12) receptor inhibitor is the
      cornerstone of treatment for patients with acute coronary syndrome and in those
      undergoing percutaneous coronary intervention. Clopidogrel is the most widely
      used P2Y(12) receptor inhibitor. Despite the clinical benefits associated with
      adjunctive clopidogrel therapy, a considerable number of patients continue to
      experience recurrent cardiovascular events. Importantly, the interindividual
      response to clopidogrel is variable and is affected by multiple factors,
      including genetic polymorphisms and drugs that interfere with the conversion of
      clopidogrel to its active metabolite. The individual variability to clopidogrel
      induced antiplatelet effects has significant clinical implications that can
      result in an increased risk of atherothrombotic recurrences, including stent
      thrombosis. The introduction of novel P2Y(12) receptor inhibitors, such as
      prasugrel or ticagrelor, characterized by more potent and consistent platelet
      inhibitory effects, represents an opportunity for clinicians to consider these
      alternative therapies to overcome the limitations of clopidogrel. Understanding
      the strategies and implications of switching antiplatelet treatment regimens is,
      therefore, key in the clinical setting. This article provides an overview of the
      literature on switching antiplatelet treatment strategies and practical
      considerations for the interventional cardiologist.

PMID- 22581464
TI  - The role of a medical toxicologist for assistance in the treatment of alcohol
      withdrawal syndrome.

PMID- 22581465
TI  - Understanding how data triangulation identifies acute toxicity of novel
      psychoactive drugs.
AB  - Over the last decade, there has been an increase in the availability and use of
      novel psychoactive substances (also known as "legal highs"). There is limited
      information available on the potential acute toxicity (harms) associated with the
      use of these novel psychoactive substances. Gold standard evidence, such as
      animal studies or human clinical trials, is rarely available to users or
      healthcare professionals. However, it is possible to use triangulation of data on
      the acute toxicity from multiple sources to describe the overall pattern of
      toxicity associated with a novel psychoactive substance. In this review, we will
      describe these potential data sources, which include self-reported toxicity on
      internet discussion fora, data from sub-population user surveys, data from
      regional and national poisons information services and published case reports and
      case series. We will then describe how pattern of acute toxicity associated with
      the use of the cathinone mephedrone (4-methylmethcathinone) was established using
      triangulation of these different data sources.

PMID- 22581466
TI  - Reproducibility of single-subject fMRI language mapping with AMPLE normalization.
AB  - PURPOSE: To evaluate the reproducibility of presurgical functional MRI (fMRI)
      language mapping based on test-retest scans, comparing traditional activation t
      maps to relative activation maps normalized by activation mapping as percentage
      of local excitation (AMPLE). MATERIALS AND METHODS: Language fMRI scans were
      performed by 12 healthy volunteer subjects undergoing a standard clinical
      presurgical mapping protocol in multiple independent scan sessions. Objective
      relative AMPLE activation maps were generated automatically by normalizing
      statistical t-value maps to the local peak activation amplitude within each
      functional brain region. The spatial distribution of activation was quantified
      and compared across mapping algorithms, subjects, scanners, and pulse sequences.
      RESULTS: The spatial distribution of traditional blood oxygen level-dependent
      (BOLD) t-value statistical activation maps was highly variable in test-retest
      scans of single subjects, whereas AMPLE normalized maps were highly reproducible
      in terms of the location, hemispheric laterality, and spatial extent of relative
      activation. AMPLE map reproducibility was good regardless of scanner, field
      strength, or pulse sequence used, but reproducibility was best for scans acquired
      on the same scanner using the same pulse sequence. CONCLUSION: Reproducibility of
      the spatial pattern of BOLD activation makes relative amplitude fMRI mapping a
      useful normalization tool for clinical imaging of language function, where
      reproducibility and quantitative measurements are critical concerns.

PMID- 22581467
TI  - Study of the mechanism of catalytic activity of G. sulfurreducens biofilm anodes
      during biofilm growth.
AB  - The number of investigations involving bioelectrochemical systems (BES),
      processes in which microorganisms catalyze electrode reactions, is increasing
      while their mechanisms remain unresolved. Geobacter sulfurreducens strain DL1 is
      a model electrode catalyst that forms multimicrobe-thick biofilms on anodes that
      catalyze the oxidation of acetate to result in an electric current. Here, we
      report the characterization by cyclic voltammetry (CV) of DL1 biofilm-modified
      anodes (biofilm anodes) performed during biofilm development. This
      characterization, based on our recently reported model of biofilm anode catalytic
      activity, indicates the following. 1) As a biofilm grows, catalytic activity
      scales linearly with the amount of anode-accessible redox cofactor in the
      biofilm. This observation is consistent with a catalytic activity that is limited
      during biofilm growth by electron transport from within cells to the
      extracellular redox cofactor. 2) Distinct voltammetric features are exhibited
      that reflect the presence of a redox cofactor expressed by cells that initially
      colonize an anode that is not involved in catalytic current generation.

PMID- 22581468
TI  - Extracellular matrix and platelet function in patients with musculocontractural
      Ehlers-Danlos syndrome caused by mutations in the CHST14 gene.
AB  - We report on a consanguineous, Afghani family with two sisters affected with
      characteristic facial features, multiple contractures, progressive joint and skin
      laxity, hemorrhagic diathesis following minor trauma and multisystem fragility
      related manifestations suggestive of a diagnosis of musculocontractural Ehlers
      Danlos syndrome (EDS). This novel form of connective tissue disorder was recently
      reported in patients of Japanese, Turkish, and Indian descent who were formerly
      classified as having EDS type VIB and has now been recognized to be a part of
      spectrum including patients previously classified as having adducted thumb
      clubfoot syndrome. We identified a previously unreported mutation in the CHST14
      gene, which codes for the enzyme dermatan 4-O-sulfotransferase. We discuss the
      prenatal presentation, detailed clinical manifestations, and neurological
      findings in two sisters with this newly described musculocontractural EDS-CHST14
      type. We demonstrate that fibroblasts from one of our patients produce more
      chondroitin sulfate than normal and show lower than normal deposition of
      collagens I and II and fibrillin 1-containing microfibrills. These findings
      suggest that the imbalance in the glycosaminoglycan content in developing tissues
      might interfere with normal deposition of other extracellular matrix components
      and ultimately contribute to the development of the phenotype observed in these
      patients. Furthermore, we ruled out the contribution of intrinsic platelet
      factors to the bleeding diathesis observed in some affected individuals.

PMID- 22581469
TI  - Development strategies for IVIVC in an industrial environment.
AB  - Product development is typically challenging. There is a strong desire to
      understand critical performance factors early in order to optimize formulations
      for Phase III trials or marketing approval. However, over 90% of drugs entering
      development in humans do not make it to the market. Thus there is a tremendous
      risk that resources spent early in development will be wasted as candidates
      attrite. To overcome this apparent dilemma, a Bayesian approach is suggested. In
      'traditional' product development, clinical study designs are typically
      relatively assumption free and often do not consider learning from earlier
      investigations. A Bayesian approach is one in which prior information is
      considered when interpreting the results of the current study. A candidate IVIVC
      can be developed at the earliest stage of clinical development. Subsequently
      there are multiple opportunities within a typical development program to assess
      the performance of the preliminary IVIVC as new formulations are introduced. With
      each introduction, there is an opportunity to either confirm the adequacy of the
      IVIVC or to identify the need for development of a more predictive dissolution
      test and IVIVC.

PMID- 22581470
TI  - The transradial versus the transfemoral approach for primary percutaneous
      coronary intervention in patients with acute myocardial infarction: a systematic
      review and meta-analysis.
AB  - AIMS: There is an increasing amount of data suggesting that transradial approach
      is associated with lower incidence of complications in vascular access site and
      improved clinical outcomes compared with transfemoral approach in the setting of
      ST-segment elevation myocardial infarction (STEMI). The objective of this study
      was to assess the safety and efficacy of radial versus femoral percutaneous
      coronary intervention (PCI) for patients with STEMI. METHODS AND RESULTS: We
      searched MEDLINE, EMBASE, and Cochrane databases for randomised, case-control,
      and cohort studies comparing access-related complications and clinical outcomes
      from January 2001 to October 2011. Twenty-one studies involving 8,534 patients
      were identified. Transradial approach was associated with a significant
      reductions in major adverse cardiac events (odds ratio [OR] 0.56, 95% confidence
      interval [CI] 0.44-0.72, p<0.001), mortality (OR 0.55, 95% CI 0.42-0.72,
      p<0.001), and major bleeding (OR 0.32, 95% CI 0.22-0.48, p<0.001) compared to
      transfemoral approach. There was a shorter hospital length of stay with
      transradial access with a weighted mean difference of 2.23 days (95% CI -3.32-
      1.14, p<0.001) compared to transfemoral access. There were no differences in
      fluoroscopic time, door-to-balloon time, and procedure time between the two
      access routes (p=0.09, p=0.38, p=0.82, respectively). The rate of access site
      crossover tended to be higher with transradial access (p=0.06). CONCLUSIONS: This
      updated meta-analysis demonstrates that transradial PCI reduces the risk of
      significant periprocedural bleeding and improve clinical outcomes in patients
      with STEMI.

PMID- 22581471
TI  - The shape of a hole and that of the surface-with-hole cannot be analyzed
      separately.
AB  - Figure-ground organization has a central role in visual perception, since it
      creates the regions to which properties, such as shape descriptions, are then
      assigned. However, there is disagreement on how much shape analysis is
      independent of figure-ground. The reversal of figure-ground of a single closed
      region is the purest form of figure-ground organization, and the two resulting
      percepts are that of an object and that of a hole. Both object and hole are
      nonaccidental regions and can share an identical outline. We devised a test of
      how figure-ground and contour ownership dramatically affect how shape is
      processed. Observers judged the shape of a contour that could be either the same
      as or different from an irrelevant surrounding contour. We report that different
      (incongruent) inside and outside contours produce a stronger interference effect
      when they form a single object-with-hole, as compared with a hierarchical set of
      surfaces or a single hole separating different surfaces (a trench). We conclude
      that (1) which surface owns the contour constrains the interference between
      shapes and that (2) despite some recent claims, holes do not display objectlike
      properties.

PMID- 22581472
TI  - Personal views about aging among Korean American older adults: the role of
      physical health, social network, and acculturation.
AB  - Given the importance of a positive attitude towards one's own aging, we examined
      its predictors in a sample of 230 Korean American older adults (M (age) = 69.8
      years, SD = 7.05). Personal views about aging, measured with a subscale of the
      Philadelphia Geriatric Center Morale Scale (PGCMS), were regressed on demographic
      variables, physical health-related factors, and psychosocial attributes (social
      network and acculturation). Results from the hierarchical regression analysis
      showed that better physical health conditions (fewer chronic conditions, less
      functional disability, and better vision) were associated with more positive
      personal views about aging. Other significant contributors included larger social
      networks and higher levels of acculturation. Findings suggest that personal views
      about aging among immigrant elderly populations can be enhanced by promoting
      physical health, social connectedness, and acculturation. Ways to maintain and
      improve positive attitudes about personal aging are discussed in a cultural
      context.

PMID- 22581473
TI  - A truncating mutation of Alms1 reduces the number of hypothalamic neuronal cilia
      in obese mice.
AB  - Primary cilia are ubiquitous cellular antennae whose dysfunction collectively
      causes various disorders, including vision and hearing impairment, as well as
      renal, skeletal, and central nervous system anomalies. One ciliopathy, Alstrom
      syndrome, is closely related to Bardet-Biedl syndrome (BBS), sharing amongst
      other phenotypic features morbid obesity. As the cellular and molecular links
      between weight regulation and cilia are poorly understood, we used the obese
      mouse strain foz/foz, bearing a truncating mutation in the Alstrom syndrome
      protein (Alms1), to help elucidate why it develops hyperphagia, leading to early
      onset obesity and metabolic anomalies. Our in vivo studies reveal that Alms1
      localizes at the base of cilia in hypothalamic neurons, which are implicated in
      the control of satiety. Alms1 is lost from this location in foz/foz mice,
      coinciding with a strong postnatal reduction (~70%) in neurons displaying cilia
      marked with adenylyl cyclase 3 (AC3), a signaling protein implicated in obesity.
      Notably, the reduction in AC3-bearing cilia parallels the decrease in cilia
      containing two appetite-regulating proteins, Mchr1 and Sstr3, as well as another
      established Arl13b ciliary marker, consistent with progressive loss of cilia
      during development. Together, our results suggest that Alms1 maintains the
      function of neuronal cilia implicated in weight regulation by influencing the
      maintenance and/or stability of the organelle. Given that Mchr1 and Sstr3
      localization to remaining cilia is maintained in foz/foz animals but known to be
      lost from BBS knockout mice, our findings suggest different molecular etiologies
      for the satiety defects associated with the Alstrom syndrome and BBS
      ciliopathies.

PMID- 22581474
TI  - Highly enantioselective epoxidation of multisubstituted enones catalyzed by non
      heme iron catalysts.
AB  - Iron(II) efficiency: The iron complexes of N(4) ligands, derived from proline and
      benzimidazole, exhibited an unprecedented activity and enantioselectivity for the
      epoxidation of a variety of di- and trisubstituted enones (see scheme). This
      system, based on synthetic non-heme iron catalysts, provides ready access to a
      wide range of epoxyketones of high enantiomeric purity.

PMID- 22581475
TI  - Typical renal-coloboma syndrome phenotype in a patient with a submicroscopic
      deletion of the PAX2 gene.
AB  - We present a patient with optic nerve hypoplasia, secondary strabismus, mild
      deafness, abnormal external ear helices, and renal hypoplasia. The clinical
      phenotype was consistent with renal-coloboma syndrome, but no point mutation in
      the PAX2 gene could be identified. High-resolution array comparative genomic
      hybridization (aCGH) analysis showed that this patient has a submicroscopic
      deletion on chromosome 10, affecting the entire coding region of the PAX2 gene.
      This finding provided the molecular confirmation of the patient's clinical
      diagnosis and showed that, in addition to point mutations, deletions of the PAX2
      gene contribute to the etiology of the renal-coloboma syndrome.

PMID- 22581476
TI  - Collaborative gaze channelling for improved cooperation during robotic assisted
      surgery.
AB  - The use of multiple robots for performing complex tasks is becoming a common
      practice for many robot applications. When different operators are involved,
      effective cooperation with anticipated manoeuvres is important for seamless,
      synergistic control of all the end-effectors. In this paper, the concept of
      Collaborative Gaze Channelling (CGC) is presented for improved control of
      surgical robots for a shared task. Through eye tracking, the fixations of each
      operator are monitored and presented in a shared surgical workspace. CGC permits
      remote or physically separated collaborators to share their intention by
      visualising the eye gaze of their counterparts, and thus recovers, to a certain
      extent, the information of mutual intent that we rely upon in a vis-a-vis working
      setting. In this study, the efficiency of surgical manipulation with and without
      CGC for controlling a pair of bimanual surgical robots is evaluated by analysing
      the level of coordination of two independent operators. Fitts' law is used to
      compare the quality of movement with or without CGC. A total of 40 subjects have
      been recruited for this study and the results show that the proposed CGC
      framework exhibits significant improvement (p < 0.05) on all the motion indices
      used for quality assessment. This study demonstrates that visual guidance is an
      implicit yet effective way of communication during collaborative tasks for
      robotic surgery. Detailed experimental validation results demonstrate the
      potential clinical value of the proposed CGC framework.

PMID- 22581477
TI  - Estimating electrical conductivity tensors of biological tissues using
      microelectrode arrays.
AB  - Finding the electrical conductivity of tissue is highly important for
      understanding the tissue's structure and functioning. However, the inverse
      problem of inferring spatial conductivity from data is highly ill-posed and
      computationally intensive. In this paper, we propose a novel method to solve the
      inverse problem of inferring tissue conductivity from a set of transmembrane
      potential and stimuli measurements made by microelectrode arrays (MEA). We first
      formalize the discrete forward model of transmembrane potential propagation,
      based on a reaction-diffusion model with an anisotropic inhomogeneous electrical
      conductivity-tensor field. Then, we propose a novel parallel optimization
      algorithm for solving the complex inverse problem of estimating the electrical
      conductivity-tensor field. Specifically, we propose a single-step approximation
      with a parallel block-relaxation optimization routine that simplifies the joint
      tensor field estimation problem into a set of computationally tractable
      subproblems, allowing the use of efficient standard optimization tools. Finally,
      using numerical examples of several electrical conductivity field topologies and
      noise levels, we analyze the performance of our algorithm, and discuss its
      application to real measurements obtained from smooth-muscle cardiac tissue,
      using data collected with a high-resolution MEA system.

PMID- 22581478
TI  - Stress state and strain rate dependence of the human placenta.
AB  - Maternal trauma (MT) in automotive collisions is a source of injury, morbidity,
      and mortality for both mothers and fetuses. The primary associated pathology is
      placental abruption in which the placenta detaches from the uterus leading to
      hemorrhaging and termination of pregnancy. In this study, we focused on the
      differences in placental tissue response to different stress states (tension,
      compression, and shear) and different strain rates. Human placentas were obtained
      (n = 11) for mechanical testing and microstructure analysis. Specimens (n = 4+)
      were tested in compression, tension, and shear, each at three strain rates (nine
      testing protocols). Microstructure analysis included scanning electron
      microscopy, histology, and interrupted mechanical tests to observe tissue
      response to various loading states. Our data showed the greatest stiffness in
      tension, followed by compression, and then by shear. The study concludes that
      mechanical behavior of human placenta tissue (i) has a strong stress state
      dependence and (ii) behaves in a rate dependent manner in all three stress
      states, which had previously only been shown in tension. Interrupted mechanical
      tests revealed differences in the morphological microstructure evolution that was
      driven by the kinematic constraints from the different loading states.
      Furthermore, these structure-property data can be used to develop high fidelity
      constitutive models for MT simulations.

PMID- 22581479
TI  - The influence of mixing methods and disinfectant on the physical properties of
      alginate impression materials.
AB  - The aims of this in vitro study were to quantify the effect of manual versus
      automatic mixing and of using a disinfectant on mechanical properties of three
      different alginate impression materials. Two of the three alginates tested were
      especially developed for orthodontic use: Orthotrace(r) and Orthofine(r) while
      the third was a conventional alginate CA37FS(r). Alginates were mixed by hand or
      automatically using a Cavex alginate mixer II(r). Mixing was performed at room
      temperature using tap water. The material was allowed to set in a water bath at
      35 degrees C (+/-1 degrees C), simulating intra-oral setting conditions, and half
      of the samples were disinfected before testing. For each tested material, 10
      standardized samples were used. The disinfectant used was the CavexImpreSafe(r)
      that has a bactericide, virucide, and fungicide function. The specimens were
      exposed for 3 minutes in a 3% solution and were then tested according to the ISO
      1563: 1990 (E) standard specifications. Descriptive statistics and three-way
      analysis of variance were performed, and a 5% significance level was used for
      statistical analysis. Evaluation of tensile strength and elastic recovery of
      different alginate samples, hand versus automatical mixing or disinfected versus
      not disinfected, resulted in significant differences for all materials except for
      Orthofine(r). Considering detail reproduction, all three alginates evaluated
      reproduced the 50-MUm line successfully without interruption. The mixing method
      can significantly affect the elastic recovery and tensile strength of the
      alginates tested while the effect of using a disinfectant is less explicit.

PMID- 22581480
TI  - Theory-informed health promotion: seeing the bigger picture by looking at the
      details.

PMID- 22581481
TI  - Triacylglycerol accumulation and change in fatty acid content of four marine
      oleaginous microalgae under nutrient limitation and at different culture ages.
AB  - Alteration of lipid biosynthesis is one of important biochemical changes when
      oleaginous microalgae grow under varied environmental conditions. The effects of
      culture age and nutrient limitation on triacylglycerol (TAG) accumulation and
      fatty acid content were investigated in four eicosapentaenoic acid (EPA)-rich
      marine microalgae. The amounts of TAGs in Chaetoceros sp., Phaeodactylum
      tricornutum and Nannochloropsis oculata increased sharply from day 4 to day 11,
      and then the former two remained nearly unchanged while the latter declined
      gradually during the batch culture. In contrast, no marked increase in TAG
      accumulation was observed in Pavlova viridis during the culture. Changes in total
      fatty acid (TFA) content mirrored those observed for TAG accumulation, while the
      EPA content reached a maximum generally at day 7 or 11 in the range of 11 - 32 mg
      g(-1) dry cell weight (DCW) and then declined. Nitrogen limitation led to a
      gradual increase in the amounts of TAGs from N. oculata pronouncedly but almost
      no change in other three species. The TFA content of the cultures after 5 days of
      nitrogen limitation was nearly twice that after 1 day in Chaetoceros sp., P.
      tricornutum and P. viridis, while the lowest increase (220 - 283 mg g(-1) DCW)
      was observed in N. oculata. TAGs increased gradually under phosphorus limitation
      in all four species but not sharply compared with that under nitrogen limitation
      in N. oculata. The TFA content increased gradually under phosphorus limitation
      and after 5 days of phosphorus limitation it was 1.5 - 2 times that after 1 day.
      The EPA content was generally not significantly affected by nitrogen or
      phosphorus limitation. Culture age and nutrient limitation could be useful
      variables for optimizing TAG accumulation and fatty acid content with potential
      for biodiesel production.

PMID- 22581482
TI  - Avoidance, safety behavior, and reassurance seeking in generalized anxiety
      disorder.
AB  - BACKGROUND: The behavioral symptoms of Generalized Anxiety Disorder (GAD) are not
      well characterized. This study examines behavioral symptoms in patients with GAD
      compared to healthy participants, their change during behavioral therapy, and
      their role for predicting short- and long-term outcome. METHODS: Secondary data
      analysis of 56 patients with DSM-IV GAD from a randomized controlled trial
      testing worry exposure (n = 29) and applied relaxation (n = 27), compared to 33
      demographically matched healthy participants. Participants reported on attempts
      to control or prevent worry, specifically cognitive and behavioral avoidance,
      safety behavior, and reassurance, along with other GAD symptoms. The Hamilton
      Anxiety Scale served as immediate (post therapy) and the Penn State Worry
      Questionnaire as immediate and long-term (6-/12-month follow-up) treatment
      outcome measure. RESULTS: GAD patients engage significantly more in attempts to
      control or prevent worry as reflected in cognitive and behavioral avoidance,
      safety behavior, and reassurance seeking than healthy comparison participants.
      Behavior therapy significantly reduces these behavioral strategies without
      substantial indication of differential effects of treatment type. However, only
      patients remitting from GAD reach the low symptom level of healthy participants.
      The initial level of behavioral symptoms is irrelevant for immediate treatment
      success, but higher degrees of cognitive and behavioral avoidance and safety
      behavior at the end of treatment predict worse long-term outcome. CONCLUSIONS:
      Behavioral symptoms appear to be relevant features in GAD that improve with
      successful treatment. Further research is warranted to examine whether inclusion
      of behavioral symptoms in the definition of GAD would have beneficial effects on
      diagnostic recognition and treatment.

PMID- 22581483
TI  - Accuracy of computer algorithms and the human eye in scoring actigraphy.
AB  - PURPOSE: The purpose of this study is to determine the optimal scoring method and
      parameter settings of actigraphy by comparison to simultaneous polysomnography
      (PSG). METHODS: Fifteen studies of simultaneous PSG and actigraphy were completed
      in adolescents (mean age = 16.3 years) and analyzed. Scoring actigraphy by the
      human eye was compared to a commercial computerized algorithm using various
      parameters. The PSG was considered the reference standard. RESULTS: There was a
      better correlation between actigraphy and PSG sleep start/end, total sleep time,
      wake after sleep onset, and sleep efficiency when the rest period was determined
      by the human (mean r = 0.640) rather than auto-set by the software (r = 0.406).
      The best results came when the rest intervals were set based on the PSG (r =
      0.694). Scoring the printed actogram by the human eye was superior to the auto
      analyses as well (r = 0.575). Higher correlations and lower biases were obtained
      from lower wake threshold settings (low and medium) and higher immobility times
      (10 and 15 min). CONCLUSIONS: Visual scoring by simple inspection of the
      actigraphy tracing had a reasonable correlation with the gold standard PSG.
      Accurate determination of the rest interval is important in scoring actigraphy.
      Scoring actigraphy by the human eye is superior to this computer algorithm when
      auto-setting major rest periods. A low wake threshold and 10-15 min of immobility
      for sleep onset and sleep end yield the most accurate computerized results. Auto
      setting major rest intervals should be avoided to set start/end of rest
      intervals; adjustments for artifacts and/or a sleep diary for comparison are
      helpful.

PMID- 22581484
TI  - Case-control studies of novel hemoglobin anomalies as differential diagnosis in
      sleep apnea syndrome.
AB  - PURPOSE: Pulse oximetry plays an essential role in the diagnosis of sleep apnea
      syndrome. We discovered two novel hemoglobin anomalies, Hb Bonn and Hb Venusberg,
      which initially resulted in avoidable sleep disorder examinations and therapeutic
      consequences due to their low oxygen saturation levels as measured by pulse
      oximetry. METHODS: Hematological as well as clinical chemical diagnosis was
      carried out. Hemoglobin anomalies were detected through electrophoresis,
      chromatography, spectrophotometry, and pulse oximetry as well as hemoglobin gene
      sequencing. RESULTS: Hb Bonn is a novel hemoglobin mutation of the proximal
      alpha1 globin with an additional absorption maximum of the oxyhemoglobin at 668
      nm. This results in pulse oximetry measurements of false low oxygen saturation
      due to incorrect calculations at the pulse oximetry measuring point 660 m. Hb
      Venusberg is a novel oxygen-affine hemoglobin mutation of the beta-globin which
      is electrophoretically silent. Clinical symptoms include intermittent low oxygen
      saturation levels, cyanosis of lips and nail beds, and limited physical
      resistance to stress. CONCLUSIONS: Hemoglobin anomalies, such as Hb Bonn and Hb
      Venusberg, should be included in differential diagnosis as potential causes of
      low oxygen saturation especially in case of nonspecific or conflicting findings.

PMID- 22581485
TI  - Treatment of obstructive sleep apnea using a custom-made titratable duobloc oral
      appliance: a prospective clinical study.
AB  - PURPOSE: This prospective clinical study investigates the efficacy of a specific
      custom-made titratable mandibular advancement device (MAD) for the treatment of
      obstructive sleep apnea (OSA). This MAD has attachments in the frontal teeth area
      that allow for progressive titration of the mandible. METHODS: Sixty-one adult
      OSA patients were included (age, 46.7 +/- 9.0 years; male/female ratio, 45/16;
      apnea-hypopnea index (AHI), 23.2 +/- 15.4 events/h sleep; body mass index, 27.9
      +/- 4.1 kg/m2). After an adaptation period, titration started based on a protocol
      of symptomatic benefit or upon reaching the physiological limits of protrusion.
      As a primary outcome, treatment response was defined as an objective reduction in
      AHI following MAD treatment of >=50 % compared to baseline, and treatment success
      as a reduction in AHI with MAD to less than 5 and 10 events/h sleep. Compliance
      failure was defined as an inability to continue treatment. RESULTS: A
      statistically significant decrease was observed in AHI, from 23.4 +/- 15.7 at
      baseline to 8.9 +/- 8.6 events/h with MAD (p < 0.01). Treatment response was
      achieved in 42 out of 61 patients (68.8 %), whereas 42.6 % met criteria of AHI <
      5 and 63.9 % achieved an AHI < 10 events/h sleep, respectively. Four patients
      (6.6 %) were considered as "compliance failures." CONCLUSIONS: The present study
      has evaluated the efficacy of a specific custom-made titratable MAD in terms of
      sleep apnea reduction.

PMID- 22581486
TI  - Integrating drug permeability with dissolution profile to develop IVIVC.
AB  - In this review article, three different approaches to predict in vivo oral
      absorption based on the in vitro data of drug permeability, solubility and
      dissolution were introduced. At the drug discovery stage, the absorption
      potential of each candidate is most important to select better compounds for
      further development. The concept of maximum absorbable dose is applied widely,
      not only to evaluate the absorption potential but also to elucidate the rate
      limiting process of oral absorption that helps us to understand the cause of poor
      absorption. To integrate the permeability of the drug with its dissolution
      profile, two different approaches, in vitro dissolution/permeation system (D/P
      system) and in silico model and simulation method, are proposed. In the D/P
      system, by mimicking the in vivo process of drug absorption, the permeated amount
      of drugs, that is the total output of dissolution and permeation processes, are
      correlated with the fraction absorbed in human (F(a)). This system is powerful
      for evaluating the improved absorption by various formulations and the effect of
      food intake. On the other hand, in the model and simulation approach, an
      intrinsic dissolution parameter of drug particle, z, was extracted from the small
      scale in vitro test and the process of intestinal absorption was re-constructed
      in silico by incorporating the physiological parameters in human. The effective
      use of these approaches for the development of oral drug products is discussed
      through various case studies.

PMID- 22581487
TI  - Using entertainment-education to promote cervical cancer screening in Thai women.
AB  - Southeast Asian women in California have high cervical cancer incidence and
      mortality rates, but low levels of Pap screening. No published reports have
      addressed screening among Thai women. Entertainment-education (EE) is a useful
      strategy for low-literacy, culturally diverse populations. This quasi
      experimental study determined whether a soap-opera-themed, Thai-language EE video
      was superior to a print handout for increasing knowledge, attitudes, and
      behavioral intention toward Pap testing. No uniform differences were found
      between the intervention group (video) and the control group (brochure). Both
      educational modalities appeared to result in selected increases in knowledge and
      attitudes.

PMID- 22581488
TI  - Nine-month results of the REFORM study: a prospective, single-arm, multicenter
      clinical study of the safety and effectiveness of the FormulaTM balloon
      expandable stent for treatment of renal artery stenosis.
AB  - OBJECTIVES: To evaluate the 9-month safety and effectiveness outcomes of the
      FormulaTM balloon-expandable renal stent (Cook Medical, Bloomington, IN) for the
      treatment of atherosclerotic renal artery stenosis (RAS) following suboptimal
      angioplasty. BACKGROUND: Atherosclerotic RAS can cause hypertension and ischemic
      nephropathy. When clinically indicated, an interventional approach with renal
      angioplasty and stent implantation is the preferred method for revascularization
      of atherosclerotic renal artery stenoses. METHODS: The REFORM study is a
      prospective, multicenter, single-arm study of stent implantation following
      suboptimal PTRA using the Formula stent. One hundred patients with
      atherosclerotic ostial renal artery lesions =18 mm in length with a >50% residual
      stenosis following PTA were enrolled. The primary endpoint was 9-month primary
      patency. RESULTS: The 9-month primary patency rate was 91.7%. The 9-month major
      adverse event rate was 2.2%. Mean systolic blood pressure was significantly
      decreased at follow-up (from 150 +/- 21 mm Hg at baseline to 141 +/- 21 mm Hg at
      9 months; P = 0.003). Mean serum creatinine (SCr) level and mean estimated
      glomerular filtration rate (eGFR) were not significantly different at 9 months. A
      clinically meaningful improvement in renal function (i.e., =25% increase in eGFR
      or =0.5 mg/dl decrease in SCr) was observed in 9% of patients at 1 month and 12%
      of patients at 9 months. A clinically meaningful decline in renal function (i.e.,
      =25% decrease in eGFR or =0.5 mg/dl increase in SCr) was observed in only 3% of
      patients at 1 month and 7% of patients at 9 months. CONCLUSIONS: The Formula
      stent was safe and effective in treating atherosclerotic RAS following suboptimal
      angioplasty.

PMID- 22581489
TI  - Optical coherence tomography for guidance of distal cell recrossing in
      bifurcation stenting: choosing the right cell matters.
AB  - AIMS: The aim of this study was to assess the ability of optical coherence
      tomography (OCT) to guide recrossing during percutaneous coronary interventions
      in bifurcations and to reduce strut malapposition. METHODS AND RESULTS: Fifty-two
      patients undergoing elective treatment of bifurcation lesions using provisional
      stenting as default strategy were included in the study. Patients were divided
      into two groups: OCT-guided stent recrossing (group 1, n=12), and angiography
      guided recrossing (group 2, n=40). Malapposition in the various bifurcation
      segments was compared in the two groups, using propensity score analysis to
      correct for confounders. In 4/12 patients (33%) of the OCT-guided group after the
      first attempt to recross the stent towards the SB the wire was found to have
      crossed in a proximal cell, requiring a second and in one case a third attempt to
      successfully cross through a distal cell. Patients who were treated using OCT
      guided recrossing had a significantly lower number of malapposed stent struts,
      especially in the quadrants towards the SB ostium (9.5%[7.5-17.4%] vs 42.3%[31.2
      54.7%] in the angiography-guided group, p<0.0001). CONCLUSIONS: The rate of strut
      malapposition was significantly reduced when OCT was used to confirm that wire
      recrossing was performed in a distal cell of the SB ostium.

PMID- 22581490
TI  - Ex vivo pharmacology of surgical samples of the uterosacral ligament. Part I:
      Effects of carbachol and oxytocin on smooth muscle.
AB  - AIMS: In a previous study we observed impaired smooth muscle in the uterosacral
      ligament (USL) of patients with pelvic organ prolapse. The aims of the study were
      to describe the method of the novel microperfusion system and to determine normal
      function and pharmacology of smooth muscle in the USL. METHODS: Samples from the
      USL were obtained during hysterectomy for benign reasons. Small stretches of
      connective tissue were mounted in a perfusion chamber under the stereomicroscope.
      Isotonic contractions of smooth muscle were monitored by digital time-lapse video
      and quantified by image processing. RESULTS: Constant perfusion with carbachol
      elicited tonic and pulse stimulation with carbachol and oxytocin rhythmic
      contractions of smooth muscle in the ground reticulum. Under constant perfusion
      with relaxin the tonic contraction after carbachol was abolished. CONCLUSIONS:
      With the novel microperfusion system, isotonic contractions of smooth muscle in
      the USL can be recorded and quantified in the tissue microenvironment on the
      microscopic level. The USL smooth muscle is cholinergic, stimulated by oxytocin
      and modulated by relaxin.

PMID- 22581491
TI  - A fundamental principle governing populations.
AB  - Proposed here is that an overriding principle of nature governs all population
      behavior; that a single tenet drives the many regimes observed in nature
      exponential--like growth, saturated growth, population decline, population
      extinction, and oscillatory behavior. The signature of such an all embracing
      principle is a differential equation which, in a single statement, embraces the
      entire panoply of observations. In current orthodox theory, this diverse range of
      population behaviors is described by many different equations-each with its own
      specific justification. Here, a single equation governing all the regimes is
      proposed together with the principle from which it derives. The principle is: The
      effect on the environment of a population's success is to alter that environment
      in a way that opposes the success. Experiments are suggested which could validate
      or refute the theory. Predictions are made about population behaviors.

PMID- 22581492
TI  - Age of acquisition estimates for 3,000 disyllabic words.
AB  - Age of acquisition (AoA) ratings based on a 1-7 scale for 3,000 disyllabic words
      were obtained from 32 participants. We demonstrate that these estimates are both
      reliable and valid. These estimates add to those collected on monosyllabic words
      and are of value to researchers interested in factors that contribute to word
      processing. They also can be used in regression analyses on measures obtained
      from large databases, and can be used in conjunction with imageability ratings
      for the same word corpus to differentiate AoA from imageability.

PMID- 22581493
TI  - Age-of-acquisition ratings for 30,000 English words.
AB  - We present age-of-acquisition (AoA) ratings for 30,121 English content words
      (nouns, verbs, and adjectives). For data collection, this megastudy used the Web
      based crowdsourcing technology offered by the Amazon Mechanical Turk. Our data
      indicate that the ratings collected in this way are as valid and reliable as
      those collected in laboratory conditions (the correlation between our ratings and
      those collected in the lab from U.S. students reached .93 for a subsample of
      2,500 monosyllabic words). We also show that our AoA ratings explain a
      substantial percentage of the variance in the lexical-decision data of the
      English Lexicon Project, over and above the effects of log frequency, word
      length, and similarity to other words. This is true not only for the lemmas used
      in our rating study, but also for their inflected forms. We further discuss the
      relationships of AoA with other predictors of word recognition and illustrate the
      utility of AoA ratings for research on vocabulary growth.

PMID- 22581494
TI  - Computer-based assessment of student-constructed responses.
AB  - Student-constructed responses, such as essays, short-answer questions, and think
      aloud protocols, provide a valuable opportunity to gauge student learning
      outcomes and comprehension strategies. However, given the challenges of grading
      student-constructed responses, instructors may be hesitant to use them. There
      have been major advances in the application of natural language processing of
      student-constructed responses. This literature review focuses on two dimensions
      that need to be considered when developing new systems. The first is type of
      response provided by the student-namely, meaning-making responses (e.g., think
      aloud protocols, tutorial dialogue) and products of comprehension (e.g., essays,
      open-ended questions). The second corresponds to considerations of the type of
      natural language processing systems used and how they are applied to analyze the
      student responses. We argue that the appropriateness of the assessment protocols
      is, in part, constrained by the type of response and researchers should use
      hybrid systems that rely on multiple, convergent natural language algorithms.

PMID- 22581495
TI  - A rich history of scientific and educational contributions: celebrating 125 years
      of the American Association of Anatomists.

PMID- 22581496
TI  - The anatomical school of Padua.
AB  - The University of Padua is one of the most ancient in the world, being founded in
      1222, and the most important anatomists of the XVI, XVII, and XVIII centuries
      studied and taught here. Probably, the first professor of anatomy and surgery was
      Bruno da Longobucco (c. 1200-c. 1286), who had previously studied at the Salerno
      School of Medicine. While professor in Padua, Andreas Vesalius (1514-1564)
      published De Humani Corporis Fabrica (1543), which is considered as the birth of
      the modern anatomy. Following professors were Realdo Colombo (c. 1516-1559),
      Gabriel Fallopius (1523-1562), Hieronymus Fabricius ab Aquapendente (1533-1619),
      Iulius Casserius (1552-1616), Johann Wesling (1598-1649), and Johann Georg
      Wirsung (1589-1643). Many other foreign scholars studied in the University of
      Padua, such as Thomas Linacre (c. 1460-1524), the founder of the Royal College of
      Physicians, Werner Rolfinck (1599-1673), and Olof Rudbeck (1630-1702), who
      created anatomical theatres in Germany and Sweden, respectively, on the basis of
      the Paduan model. The anatomy of the XVII century characteristically widened the
      scope of its enquiry to function, as in the Exercitatio Anatomica De Motu Cordis
      et Sanguinis in Animalibus (1628) by William Harvey (1578-1657). Further
      evolution was then given by the anatomy in the XVIII century, which tried to
      correlate alterations of structure with clinical symptoms. The most important
      anatomist of this century is Giovanni Battista Morgagni (1682-1771), whose
      masterpiece De Sedibus et Causis Morborum per Anatomen Indagatis (1761) is a
      landmark contribution that is viewed as the beginning of modern pathologic
      anatomy. This year falls the 300th anniversary of Morgagni's inaugural lecture on
      medical education, Nova Institutionum Medicarum Idea (1712), which is still
      relevant in its effort to stress the importance of a deep knowledge of all the
      preclinical and clinical aspects of medical science.

PMID- 22581498
TI  - Complex 9p rearrangement in an XY patient with ambiguous genitalia and features
      of both 9p duplication and deletion.

PMID- 22581499
TI  - Molecular characterization of protein p50 of Dendrolimus punctatus cytoplasmic
      polyhedrosis virus.
AB  - Genome segment 7 of the 10-segmented RNA genomes of Dendrolimus punctatus
      cytoplasmic polyhedrosis virus (DpCPV) comprises 1502 nucleotides with one ORF of
      1347 bp. This ORF was predicted to encode a protein of 448 amino acids with a
      molecular mass of 49,756 Da (p50). Antisera against both p50 and an antigen
      domain (AD) near the N-terminus of p50 specifically bound to a viral structural
      protein of ca. 33 kDa (V5), indicating that V5 was an N-terminal product of p50.
      Immunoblotting analysis with anti-p50 antibodies detected p50 and V5 molecules in
      the host midguts three days and five days post infection, respectively. The
      intracellular localization of p50 protein was examined by expressing truncations
      of p50 fused with GFP in recombinant baculovirus-infected Sf9 cells. The p50
      protein was present in the cytoplasm of the cells, and the N-terminal portion (67
      135 aa) of the protein played a key role in this localization.

PMID- 22581500
TI  - Symptom profiles of DSM-IV-defined remission, recovery, relapse, and recurrence
      of depression: the role of the core symptoms.
AB  - BACKGROUND: Depression outcomes in research and clinical practice are commonly
      defined by the concepts of remission, recovery, relapse, and recurrence. Despite
      their widespread use, there has been little empirical examination of these
      concepts. Therefore, we investigated profiles of individual symptoms during each
      of these phases of depression. METHODS: In a 3-year prospective study of 267
      depressed primary care patients, we established the presence or absence of the
      individual DSM-IV depressive symptoms week-by-week during DSM-IV-defined
      remissions, recoveries, relapses, and recurrences. We measured symptoms in 12
      quarterly assessments using the Composite International Diagnostic Interview.
      RESULTS: Remissions were characterized by double the proportion of time that the
      core symptoms were present compared to the initial phase of recoveries after a
      major depressive episode (MDE; 59 versus 32%; Z = -3.03; P = .002). Before a
      relapse, remissions again showed elevated levels of core symptoms in comparison
      to the final phase of recoveries before a recurrence (58 versus 26%; Z = -2.99; P
      = .003). CONCLUSIONS: Compared with the initial and final phases of recoveries,
      remissions showed a consistently higher level of core symptoms. Clinically, this
      means that unresolved core symptoms in the direct aftermath of a MDE seem to
      constitute a risk for relapse and should be the target of preventive or augmented
      interventions.

PMID- 22581501
TI  - Tools to analyse and display variations in anatomical delineation.
AB  - Variations in anatomical delineation, principally due to a combination of inter
      observer contributions and image-specificity, remain one of the most significant
      impediments to geometrically-accurate radiotherapy. Quantification of spatial
      variability of the delineated contours comprising a structure can be made with a
      variety of metrics, and the availability of software tools to apply such metrics
      to data collected during inter-observer or repeat-imaging studies would allow
      their validation. A suite of such tools have been developed which use an
      Extensible Markup Language format for the exchange of delineated 3D structures
      with radiotherapy planning or review systems. These tools provide basic
      operations for manipulating and operating on individual structures and related
      structure sets, and for deriving statistics on spatial variations of contours
      that can be mapped onto the surface of a reference structure. Use of these tools
      on a sample dataset is demonstrated together with import and display of results
      in the SWAN treatment plan review system.

PMID- 22581502
TI  - Acknowledging small acts of kindness.

PMID- 22581503
TI  - Reflections on nursing ethics.

PMID- 22581504
TI  - Nurses' experiences of violation of their dignity.
AB  - Dignity is a human right and a base for human health. This right must be observed
      in work environments as a moral obligation. This qualitative study aimed to
      understand nurses' experiences of violation of their dignity at work and to
      explore its dimensions. The participants were 15 nurses working in two hospitals
      in Tehran. The data were collected through 26 unstructured interviews and
      analyzed using content analysis. The dimensions of violation were 'irreverence',
      including experiences of abuse and violence, humiliation, and being ignored;
      'coercion and violation of autonomy', consisting of the control of relationships,
      lack of privacy, rigidness, and imposition; 'ignoring professional and scientific
      ability', indicating impossibilities in applying nurses' knowledge; and 'denying
      the value of nurse/care', being the theme that verified the dominance of
      treatment/cure and lack of recognition of care value. Health systems should take
      the promotion of the nurses' dignity into account through providing a dignified
      work environment.

PMID- 22581505
TI  - Recognition as a valued human being: perspectives of mental health service users.
AB  - The acknowledgement of basic human vulnerability in relationships between mental
      health service users and professionals working in community-based mental health
      services (in Norway) was a starting point. The purpose was to explore how users
      of these services describe and make sense of their meetings with other people.
      The research is collaborative, with researcher and person with experienced-based
      knowledge cooperating through the research process. Data is derived from 19
      interviews with 11 people who depend on mental health services for assistance at
      least three times a week. Data is analysed according to the Interpretative
      Phenomenological Analysis (IPA). Results confirm that reciprocity is fundamental
      for relationships, and that recognizing the individual entails personal
      involvement. The participants describe a struggle, and recognizing this struggle
      may help the professional to achieve a deeper understanding of the individual.

PMID- 22581506
TI  - Patients' and nurses' perceptions of respect and human presence through caring
      behaviours: a comparative study.
AB  - Although respect and human presence are frequently reported in nursing
      literature, these are poorly defined within a nursing context. The aim of this
      study was to examine the differences, if any, in the perceived frequency of
      respect and human presence in the clinical care, between nurses and patients. A
      convenience sample of 1537 patients and 1148 nurses from six European countries
      (Cyprus, Czech Republic, Finland, Greece, Hungary and Italy) participated in this
      study during autumn 2009. The six-point Likert-type Caring Behaviours Inventory
      24 questionnaire was used for gathering appropriate data. The findings showed
      statistically significant differences of nurses' and patients' perception of
      frequency on respect and human presence. These findings provide a better
      understanding of caring behaviours that convey respect and assurance of human
      presence to persons behind the patients and may contribute to close gaps in
      knowledge regarding patients' expectations.

PMID- 22581507
TI  - Personal and professional values grading among midwifery students.
AB  - The purpose of this study was to determine the professional and personal values
      among midwifery students in Turkey and to identify whether the years of study
      affected these values. A total of 192 participants were asked to prioritize 16
      professional and 36 personal values. The relationship between the year of study
      and value ranking was analyzed by Kruskal-Wallis test. The first three of the
      professional values were justice, equality, and human dignity. Equality ranked
      sixth among the personal terminal values, and it increased with the years of
      study. Of personal instrumental values, responsibility and cleanliness ranked
      second and fifth, which are of central importance for the profession of
      midwifery. However, the other two important values, privacy and preventing
      unnecessary suffering, ranked lower when the years of study increased, in other
      words when the students confront clinics. Since these values are important for
      midwifery, ethics courses should be given throughout the midwifery education to
      prepare students for the challenges they face in the clinical environment.

PMID- 22581509
TI  - Identification of human cytochrome P450 enzymes involved in the metabolism of a
      novel k-opioid receptor agonist, nalfurafine hydrochloride.
AB  - Nalfurafine hydrochloride (TRK-820) exhibits strong k-opioid agonistic activity
      and is a new antipruritic agent for uremic pruritus. This study was performed to
      identify the human hepatic cytochrome P450 isoforms involved in the metabolic
      conversion of nalfurafine to the decyclopropylmethylated form, de-CPM, using
      human liver microsomes and E. coli membrane fractions expressing human P450
      isoforms. Samples were analysed by liquid chromatography with a radioactivity
      detector and liquid chromatography-tandem mass spectrometry. The metabolism of
      nalfurafine by human liver microsomes exhibited a biphasic kinetic profile.
      Experiments examining the metabolism by E. coli membrane fractions expressing
      human P450 isoforms indicated that CYP1A1, 2C8, 2C19 and 3A4 had the ability to
      produce de-CPM. In experiments with human liver microsomes that examined the
      inhibition of nalfurafine metabolism by anti-human P450 antibodies, anti-CYP3A4
      antibody predominantly, and anti-CYP2C8 and 2C19 antibodies moderately, inhibited
      de-CPM formation. From these results, CYP3A4 appeared to be the major isoform
      involved in the metabolic decyclopropylmethylation of nalfurafine, while CYP2C8
      and 2C19 most likely play a minor role in the formation of de-CPM.

PMID- 22581510
TI  - Two-stage percutaneous closure of paravalvular leak in a patient with stentless
      aortic bioprosthesis.
AB  - We report a case of successful 2-stage percutaneous closure of severe
      paravalvular leak (PVL) in a patient with stentless aortic bioprosthesis. Threat
      of pliable prosthesis compression and long course of PVL posed main
      considerations. Accordingly, Amplatzer vascular plug (AVP) 2 was chosen as
      occluder. It was delivered transfemorally under fluoroscopy and transesophageal
      echocardiography guidance. No prosthesis distortion was provoked at the expense
      of moderate residual leak. Its symptoms after 3 months spurred another AVP 2
      implantation, which lead to PVL closure with no effect on valve area. Marked
      reduction of left ventricle cavity size and NT-proBNP plasma concentration was
      promptly noted and remains stable in 12-month follow-up.

PMID- 22581511
TI  - Effectiveness of percutaneous posterior tibial nerve stimulation for overactive
      bladder: a systematic review and meta-analysis.
AB  - AIM: To evaluate the effectiveness of posterior percutaneous tibial nerve
      stimulation (PTNS) in treating overactive bladder (OAB) symptoms by systematic
      review of the literature. METHODS: Systematic literature search was carried out
      (up to April 2011) using relevant search terms in Medline, EMBASE, CINAHL,
      CENTRAL, National Library for Health, MetaRegister of controlled trials, LILACS,
      and Google Scholar. Relevant randomized controlled trials (RCTs) and prospective
      studies were selected and then analyzed by two-independent reviewers. Meta
      analysis was performed with random effects model using STATA 8 for non-randomized
      prospective studies and with Review Manager 5.1 for RCTs. RESULTS: The studies
      report variable initial success rates (37-82%) for treating OAB symptoms with
      PTNS. Four randomized trials compared PTNS with Sham treatment showing a
      significant difference favoring PTNS [RR 7.02 95% confidence interval (CI) 1.69
      29.17]. Two randomized trials compared PTNS with antimuscarinic medication with
      no significant difference in the change in bladder diary parameters between the
      treatments. Ten prospective non-randomized studies were included. The definitions
      of success were varied. The pooled subjective success rate was 61.4% (95% CI 57.5
      71.8) and objective success rate was 60.6% (95% CI 49.2-74.7). CONCLUSION: There
      is evidence of significant improvement in OAB symptoms using PTNS which is
      comparable to the effect of antimuscarinics but with a better side effect
      profile. The studies included in the review only considered short-term outcomes
      after initial treatment. In order to recommend PTNS as a practical treatment
      option, long-term data and health economic analysis are needed.

PMID- 22581512
TI  - Organ accumulation in mice after inhalation of single or mixed essential oil
      compounds.
AB  - Essential oils are composed of multiple components. It is thought that the effect
      of essential oils is due to specific component ratios, which may differ from the
      original ratio when the essential oil is absorbed. However, very little detailed
      research exists in this area. We studied the distribution of essential oil
      components after inhalation of single and mixed components in mice. This research
      was done using four main components of Alpinia zerumbet (Pers.) B. L. Burtt. and
      R. M. Sm.: alpha-pinene, p-cymene, 1,8-cineole, and limonene. After inhalation of
      single or mixed components for 90 min, component levels in the brain and liver of
      mice were measured. The results indicated that the amount of alpha-pinene in the
      brain and liver was twofold greater after mixed-component inhalation than that
      after single-component inhalation. In a comparison of the components of the mixed
      inhalation, the ratio of alpha-pinene increased to about three times that of 1,8
      cineole. It is thought that the absorption via the nasal mucus greatly influences
      this phenomenon. The results of this investigation of the bodily distribution of
      essential oil volatile components may provide clues for elucidating their action.

PMID- 22581513
TI  - Fat-referenced MR thermometry in the breast and prostate using IDEAL.
AB  - PURPOSE: To demonstrate a three-echo fat-referenced MR thermometry technique that
      estimates and corrects for time-varying phase disturbances in heterogeneous
      tissues. MATERIALS AND METHODS: Fat protons do not exhibit a temperature
      dependent frequency shift. Fat-referenced thermometry methods exploit this
      insensitivity and use the signal from fat to measure and correct for magnetic
      field disturbances. In this study, we present a fat-referenced method that uses
      interpolation of the fat signal to correct for phase disturbances in fat free
      regions. Phantom and ex vivo tissue cool-down experiments were performed to
      evaluate the accuracy of this method in the absence of motion. Non-heated in vivo
      imaging of the breast and prostate was performed to demonstrate measurement
      robustness in the presence of systemic and motion-induced field disturbances.
      Measurement accuracy of the method was compared to conventional proton resonance
      frequency shift MR thermometry. RESULTS: In the ex vivo porcine tissue
      experiment, maximum measurement error of the fat-referenced method was reduced
      42% from 3.3 to 1.9 degrees C when compared to conventional MR thermometry. In
      the breasts, measurement errors were reduced by up to 70% from 6.4 to 1.9 degrees
      C. CONCLUSION: Ex vivo and in vivo results show that the proposed method reduces
      measurement errors in the heterogeneous tissue experiments when compared to
      conventional MR thermometry.

PMID- 22581514
TI  - Screening for autism in Mexico.
AB  - In order to conduct the screening phase of the first epidemiological survey of
      autism spectrum disorders (ASDs) in Mexico, we needed a screening tool to detect
      autistic symptomatology in a large sample of school-age children. We used the
      Spanish version of the Social Responsiveness Scale (SRS). We recruited a clinical
      sample of 200 children (81% males; mean age: 7.4 years) with a confirmed
      diagnosis of ASDs and a sample of 363 control children (59.5% males; mean age:
      8.5 years) without ASDs. Three-way analyses of variance (ANOVAs) identified a
      main effect of clinical status (ASDs vs. controls) for both parent and teacher
      scales, but no gender or age effect. The mean total and subscale raw scores were
      significantly different between the clinical and control groups for the parent
      and for the teacher SRS (P < 0.001). The internal consistency of the SRS was
      excellent. Receiver operating characteristic (ROC) analyses showed excellent
      discriminant validity of the SRS in the Mexican sample (area under the curve:
      0.962 for the parent, 0.960 for the teacher). ROC curves were also used to
      determine which cutoff would provide the best trade-off between sensitivity and
      specificity. Mexican SRS scores were significantly higher than in the U.S. and
      German population for typically developing children but comparable for clinically
      referred subjects. The SRS is an acceptable screening instrument for
      epidemiological studies of ASDs in Mexico. Its psychometric properties are
      excellent and comparable to those derived from North American and other samples.

PMID- 22581515
TI  - Relationship between plasma metalloproteinase-9 levels and volume and severity of
      infarct in patients with acute ischemic stroke.
AB  - Matrix metalloproteinases (MMP) constitute an endopeptidase family involved in
      various physiological and pathological processes. It was demonstrated that plasma
      MMP-9 level was increased in patients with acute ischemic stroke. In this study,
      it was investigated whether there was a relationship between the levels of plasma
      MMP-9 and the severity of stroke and infarct volume in patients with acute
      ischemic stroke. A total of 32 patients with acute ischemic stroke, (16 males and
      16 females) and 30 healthy controls were included in the study. Plasma MMP-9
      levels were measured using ELISA method. Computed tomography was performed at
      48th hour and infarct volume was calculated using the Cavalieri method. The
      National Institute of Health Stroke Scale (NIHSS) was checked at baseline, 12,
      24, and 48th hour. Plasma MMP-9 levels of the patient group at baseline, 12, 24,
      and 48th hour were found significantly higher compared to the control group (p <
      0.05). An important correlation between MMP-9 levels and the infarct volume was
      observed at baseline, 12, 24, and 48th hour (p < 0.001). Furthermore, a positive
      correlation was recorded between plasma MMP-9 levels and NIHSS scores at
      baseline, 12, 24, and 48th hour (p < 0.001). Plasma MMP-9 levels of those of
      suffering medium and heavy damages were found significantly higher when compared
      to those of having slight damage (p < 0.05). A significant relationship was also
      observed between infarct volumes and neurological deficits (p < 0.05). Plasma MMP
      9 levels of the patients at 48th hour were found to be significantly lower in
      recovered patients compared to those who did not improved or worsened (p < 0.05).
      A positive correlation was recorded between the infarct volume and infarct
      progression (p < 0.05). In conclusion, this study showed that plasma MMP-9 level
      substantially increased during the acute period of ischemic cerebrovascular
      disease and correlated with the severity of the disease and infarct volume. The
      definition of the exact role of plasma MMP-9 after ischemic stroke will have
      important diagnostic implications for stroke and for the development of
      therapeutic strategies aimed at modulating plasma MMP-9.

PMID- 22581516
TI  - Posterior leukoencephalopathy in NARP syndrome.

PMID- 22581517
TI  - Dual action of TGF-beta induces vascular growth in vivo through recruitment of
      angiogenic VEGF-producing hematopoietic effector cells.
AB  - The role of Transforming growth factor beta (TGF-beta) as a regulator of blood
      vessel endothelium is complicated and controversial, and the mechanisms by which
      TGF-beta is able to induce angiogenesis in vivo are not well understood. Here we
      show that TGF-beta causes in vivo a massive recruitment of tissue infiltrating
      hematopoietic cells. Concurrently, TGF-beta induces strong vascular endothelial
      growth factor (VEGF) production in the recruited hematopoietic cells, resulting
      in activated angiogenesis and vascular remodeling. TGF-beta also promoted
      abnormalities of alpha-smooth muscle actin-expressing pericytes on angiogenic
      capillaries. TGF-beta-induced angiogenic effect was inhibited by a systemic
      treatment with VEGF-neutralizing antibodies. When studied in isolated human
      hematopoietic cells, physiological concentrations of TGF-beta stimulated VEGF
      mRNA and protein expression in a dose- and time-dependent manner. This induction
      was p38 and p44/p42 mitogen activated kinase dependent. p38 and p44/p42
      activation was also observed in vivo in TGF-beta-treated angiogenic murine
      tissues. Taken together, our results provide a dual action mechanism by which TGF
      beta promotes angiogenesis in vivo via recruitment of paracrine VEGF-expressing
      hematopoietic effector cells. This mechanism may activate vascular growth and
      remodeling during inflammatory conditions and tumor growth when TGF-beta activity
      is upregulated.

PMID- 22581518
TI  - Almanac 2012: cardiovascular risk scores. The national society journals present
      selected research that has driven recent advances in clinical cardiology.

PMID- 22581519
TI  - Diagnosis and management of patients with acute cardiac symptoms, troponin
      elevation and culprit-free angiograms.
AB  - Patients with acute cardiac symptoms, elevated cardiac troponin and culprit-free
      angiograms comprise a significant proportion of patients admitted with presumed
      acute coronary syndromes (ACS). International guidelines recommend that these
      patients receive lifelong secondary prevention under the presumption that
      angiographically undetectable coronary artery disease is the likeliest cause for
      their presentation. Recent studies using cardiac MRI suggest myocarditis to be
      the most common cause of these presentations. Emerging data also suggest that
      myocarditis presenting like an ACS may not be benign. In this article the current
      literature on patients presenting with acute cardiac symptoms, elevated cardiac
      troponins but culprit-free angiograms is reviewed, focusing on the diagnostic
      utility of cardiac MRI in this cohort, and the importance of diagnosing acute
      myocarditis. The development of higher sensitivity troponin assays will
      undoubtedly lead to an increase in the number of patients with presumed ACS but
      culprit free angiography. Robust management pathways including cardiac MRI are
      vital for cardiac centres dealing with these patients in order to achieve cost
      effective, individualised patient care.

PMID- 22581520
TI  - Physiological responses of soil crust-forming cyanobacteria to diurnal
      temperature variation.
AB  - The optimum growth of soil crust-forming cyanobacterial species occurs between 21
      and 30  degrees C. When the temperature decreases below -5  degrees C, the liquid
      water in the cyanobacterial cells may freeze. In the natural environment, the
      temperature gradually decreases from autumn to winter, and the diurnal
      temperatures fluctuate enormously. It was hypothesized that the physiology of
      cyanobacterial cells changes in later autumn to acclimatize the cells to the
      upcoming freezing temperatures. In the present study, an incubation experiment in
      growth chambers was designed to stimulate the responses of cyanobacterial cells
      to diurnal temperature variations before freezing in late autumn. The results
      showed that "light" cyanobacterial soil crusts are more tolerant to diurnal
      temperature fluctuations than "dark" cyanobacterial soil crusts. After the first
      diurnal temperature cycle between 24 and -4  degrees C, the malondialdehyde (MDA)
      contents increased and the photosynthetic activity decreased. The superoxide
      dismutase activity increased, more extracellular polysaccharides (EPS) were
      secreted and the ratios of the light-harvesting and light-screening pigments
      decreased. With increasing numbers of diurnal temperature cycles, the MDA
      contents and photosynthetic activity gradually returned to their initial levels.
      Our results suggest that there are at least three pathways by which crust-forming
      cyanobacteria acclimate to the diurnal temperature cycles in the late autumn in
      the Hopq Desert, Northwest China. These three pathways include increased
      secretion of EPS, regulation of the ratios of light-harvesting and light
      screening pigments, and activation of the antioxidant system. The results also
      indicate that late autumn is a critical period for the protection and restoration
      of the cyanobacterial soil crusts in the Hopq Desert.

PMID- 22581521
TI  - The prognostic significance of tumor-associated stroma in invasive breast
      carcinoma.
AB  - Fibroblasts in the stromal component of a tumor may influence tumor progression
      in various organs. The prognostic significance of tumor-infiltrating lymphocytes
      is also frequently reported. However, the prognostic significance of the stromal
      component in breast cancers, particularly those of high grade, has not been
      established. In this study, we analyzed surgically resected specimens from 545
      patients with breast carcinoma, including 193 high-grade tumors, for tumor-stroma
      ratio, dominant stroma type [collagen (C), fibroblast (F), or lymphocyte (L)
      dominant type], and central fibrosis on hematoxylin-eosin-stained histological
      sections. We correlated these features with clinical prognosis. Among the 533
      specimens examined, 127 (23.3 %) were of C type, 292 (53.6 %) of F type, and 114
      (20.9 %) of L type. Central fibrosis was found in 99 tumors (18 %). The dominant
      stroma type was a significant prognostic factor on univariate and multivariate
      analyses, together with T classification, nodal status, and Bloom-Richardson
      grade. Tumor-stroma ratio and central fibrosis did not predict survival on
      multivariate analysis. Even in high-grade tumors, relapse-free intervals differed
      significantly according to dominant stroma type. Thus, conventional hematoxylin
      eosin-stained tumor slides may contain more prognostic information than
      previously thought; in particular, the dominant stroma type in invasive breast
      cancer may potentially be used to predict outcome.

PMID- 22581522
TI  - MicroRNA-181a promotes gastric cancer by negatively regulating tumor suppressor
      KLF6.
AB  - MicroRNAs have emerged as crucial regulators of tumorigenesis. However, it
      remains unknown whether miR-181a is involved in the pathogenesis of gastric
      cancer. In this study, we found that miR-181a is overexpressed in human gastric
      cancer tissues. Ectopic expression of miR-181a mimic promoted the proliferation,
      colony formation, migration, and invasion and inhibited the apoptosis of SGC-7901
      gastric cancer cells, whereas ectopic expression of miR-181a inhibitor inhibited
      the malignant phenotypes of SGC-7901 cells. Site-directed mutagenesis and
      luciferase reporter assay demonstrated that miR-181a repressed KLF6 expression by
      targeting its 3'-UTR. Western blot analysis further showed that KLF6 protein was
      significantly decreased or increased when miR-181a mimic or inhibitor was
      transfected into SGC-7901 cells, respectively. In summary, these data suggest
      that KLF6 gene is a direct target of miR-181a and miR-181a functions as an
      oncomir in gastric cancer by repressing the expression of tumor suppressor KLF6.

PMID- 22581523
TI  - Refining of plant oils to chemicals by olefin metathesis.
AB  - Plant oils are attractive substrates for the chemical industry. Their scope for
      the production of chemicals can be expanded by sophisticated catalytic
      conversions. Olefin metathesis is an example, which also illustrates generic
      issues of "biorefining" to chemicals. Utilization on a large scale requires high
      catalyst activities, which influences the choice of the metathesis reaction. The
      mixture of different fatty acids composing a technical-grade plant oil substrate
      gives rise to a range of products. This decisively determines possible process
      schemes, and potentially provides novel chemicals and intermediates not employed
      to date.

PMID- 22581524
TI  - Approaches for dislodged stent retrieval during transradial percutaneous coronary
      interventions.
AB  - Transradial percutaneous coronary intervention (PCI) has been associated with a
      lower incidence of major access site related complications. With the increased
      implementation of transradial approach in complex PCI, stent dislodgement is
      unavoidable in any interventionalists' career. Stent retrieval is different in a
      transradial approach as compared to a transfemoral approach because of the
      former's smaller arterial size. In this review, we outline the different stent
      retrieval techniques with considerations from transradial access.

PMID- 22581525
TI  - ENVOY is a major determinant in regulation of sexual development in Hypocrea
      jecorina (Trichoderma reesei).
AB  - Light is one crucial environmental signal which can determine whether a fungus
      reproduces asexually or initiates sexual development. Mating in the ascomycete
      Hypocrea jecorina (anamorph Trichoderma reesei) occurs preferentially in light.
      We therefore investigated the relevance of the light response machinery for
      sexual development in H. jecorina. We found that the photoreceptors BLR1 and BLR2
      and the light-regulatory protein ENV1 have no effect on male fertility, while
      ENV1 is essential for female fertility. BLR1 and BLR2 were found to impact
      fruiting body formation although they are not essential for mating. Quantitative
      reverse transcription-PCR (qRT-PCR) analyses revealed that BLR1, BLR2, and ENV1
      negatively regulate transcript levels of both pheromone receptors as well as
      peptide pheromone precursors in light but not in darkness and in a mating type
      dependent manner. The effect of BLR1 and BLR2 on regulation of pheromone
      precursor and receptor genes is less severe than that of ENV1 as strains lacking
      env1 show 100-fold (for ppg1) to more than 100,000-fold (for hpp1) increased
      transcript levels of pheromone precursor genes as well as more than 20-fold
      increased levels of hpr1, the pheromone receptor receiving the HPP1 signal in a
      MAT1-1 strain. ENV1 likely integrates additional signals besides light, and our
      results indicate that its function is partially mediated via regulation of mat1-2
      1. We conclude that ENV1 is essential for balancing the levels of genes regulated
      in a mating-type-dependent manner, which contributes to determination of sexual
      identity and fruiting body formation.

PMID- 22581529
TI  - Corticosteroids and Duchenne muscular dystrophy: does earlier treatment really
      matter?

PMID- 22581526
TI  - Identification and functional characterization of Rca1, a transcription factor
      involved in both antifungal susceptibility and host response in Candida albicans.
AB  - The identification of novel transcription factors associated with antifungal
      response may allow the discovery of fungus-specific targets for new therapeutic
      strategies. A collection of 241 Candida albicans transcriptional regulator
      mutants was screened for altered susceptibility to fluconazole, caspofungin,
      amphotericin B, and 5-fluorocytosine. Thirteen of these mutants not yet
      identified in terms of their role in antifungal response were further
      investigated, and the function of one of them, a mutant of orf19.6102 (RCA1), was
      characterized by transcriptome analysis. Strand-specific RNA sequencing and
      phenotypic tests assigned Rca1 as the regulator of hyphal formation through the
      cyclic AMP/protein kinase A (cAMP/PKA) signaling pathway and the transcription
      factor Efg1, but also probably through its interaction with a transcriptional
      repressor, most likely Tup1. The mechanisms responsible for the high level of
      resistance to caspofungin and fluconazole observed resulting from RCA1 deletion
      were investigated. From our observations, we propose that caspofungin resistance
      was the consequence of the deregulation of cell wall gene expression and that
      fluconazole resistance was linked to the modulation of the cAMP/PKA signaling
      pathway activity. In conclusion, our large-scale screening of a C. albicans
      transcription factor mutant collection allowed the identification of new
      effectors of the response to antifungals. The functional characterization of Rca1
      assigned this transcription factor and its downstream targets as promising
      candidates for the development of new therapeutic strategies, as Rca1 influences
      host sensing, hyphal development, and antifungal response.

PMID- 22581527
TI  - Topological and mutational analysis of Saccharomyces cerevisiae Fks1.
AB  - Fks1, with orthologs in nearly all fungi as well as plants and many protists,
      plays a central role in fungal cell wall formation as the putative catalytic
      component of beta-1,3-glucan synthase. It is also the target for an important new
      antifungal group, the echinocandins, as evidenced by the localization of
      resistance-conferring mutations to Fks1 hot spots 1, 2, and 3 (residues 635 to
      649, 1354 to 1361, and 690 to 700, respectively). Since Fks1 is an integral
      membrane protein and echinocandins are cyclic peptides with lipid tails, Fks1
      topology is key to understanding its function and interaction with echinocandins.
      We used hemagglutinin (HA)-Suc2-His4C fusions to C-terminally truncated
      Saccharomyces cerevisiae Fks1 to experimentally define its topology and site
      directed mutagenesis to test function of selected residues. Of the 15 to 18
      transmembrane helices predicted in silico for Fks1 from evolutionarily diverse
      fungi, 13 were experimentally confirmed. The N terminus (residues 1 to 445) is
      cytosolic and the C terminus (residues 1823 to 1876) external; both are essential
      to Fks1 function. The cytosolic central domain (residues 715 to 1294) includes
      newly recognized homology to glycosyltransferases, and residues potentially
      involved in substrate UDP-glucose binding and catalysis are essential. All three
      hot spots are external, with hot spot 1 adjacent to and hot spot 3 largely
      embedded within the outer leaflet of the membrane. This topology suggests a model
      in which echinocandins interact through their lipid tails with hot spot 3 and
      through their cyclic peptides with hot spots 1 and 2.

PMID- 22581530
TI  - The thoracic outlet syndromes.
AB  - The term thoracic outlet syndrome (TOS) refers to a heterogeneous group of
      disorders, all of which have in common compression of one or more neurovascular
      elements at some point within the thoracic outlet. Of the five disorders
      comprising this group, four have all of the features expected of a syndrome-a
      recognized constellation of clinical features; an anatomic derangement accounting
      for these features; and a method of testing that identifies the anatomic
      derangement. Consequently, their recognition and management are relatively
      straightforward. Conversely, one of these five disorders (nonspecific TOS) lacks
      these correlations, which has generated considerable debate in the literature and
      caused some experts to doubt its existence altogether. The primary focus in this
      study is on the neurologic forms of TOS. However, for completeness and a better
      understanding of these neurologic manifestations, the vascular forms are also
      reviewed.

PMID- 22581531
TI  - Early corticosteroid treatment in 4 Duchenne muscular dystrophy patients: 14-year
      follow-up.
AB  - INTRODUCTION: Corticosteroid treatment is the standard of care in Duchenne
      muscular dystrophy (DMD), but the optimal age to initiate treatment and dosage
      pattern remain a matter of discussion. METHODS: We performed a long-term study of
      alternate-day corticosteroids in five 2- to 4-year-old DMD patients. The primary
      outcome measure was prolongation of the ability to walk. RESULTS: One patient
      lost ambulation at age 10. Four patients, aged 16 to 18 were fully ambulant, and
      3 of them could still climb stairs. Respiratory function was moderately reduced
      in 2. Left ventricular ejection fraction was > 45%. Short stature and delayed
      puberty were the most relevant side effects. Although the negative impact of
      corticosteroid treatment on growth rate remained their major concern, parents and
      patients stated that they preferred corticosteroid therapy. CONCLUSIONS: Long
      term corticosteroid treatment is effective in prolonging function but not in
      recovering lost function, and its early use seems appropriate.

PMID- 22581532
TI  - A new model of experimental fibrosis in hindlimb skeletal muscle of adult mdx
      mouse mimicking muscular dystrophy.
AB  - INTRODUCTION: Duchenne Muscular Dystrophy (DMD) is characterized by the lack of
      dystrophin that leads to severe myofiber degeneration. We have shown that
      endomysial fibrosis is correlated with age at ambulation loss in DMD patients.
      However, the dystrophin-deficient mdx mouse does not have fibrotic lesions in
      adult limb muscles. Here, we describe a model of chronic mechanical muscle injury
      that triggers chronic lesions in mdx hindlimb muscle. METHODS: Micromechanical
      injuries were performed daily in tibialis anterior muscles for 2 weeks. RESULTS:
      Endomysial fibrosis appeared beginning 1 week post-injury, remained stable for 3
      months and was associated with loss of specific maximal force. Fibrosis was
      associated with an increased expression of factors involved in fibrogenesis
      including alpha-smooth muscle actin, connective tissue growth factor, and lysyl
      oxidase, which colocalized with collagen deposits. CONCLUSIONS: This induced
      fibrotic dystrophic model may be useful to study mechanisms of fibrosis in
      dystrophinopathies and to evaluate antifibrotic treatments.

PMID- 22581533
TI  - Geographical distribution of a seropositive myasthenia gravis population.
AB  - INTRODUCTION: To assess age- and sex-specific myasthenia gravis (MG) occurrence
      and incidence in the different geographical regions in Norway and thereby to
      identify factors that may contribute to the development of MG. METHODS: Multiple
      Poisson regression analysis was used to assess variation in incidence dependent
      on year, gender and onset age in five geographically defined health regions.
      RESULTS: The study population comprised 419 individuals with first time
      seropositive tests from 1995 to 2007. Annual MG incidence ranged from < 1 to 14
      per million, with an average of 7.04 per million for all five health regions
      combined. CONCLUSIONS: This is the first nation-wide epidemiological study of
      seropositive MG that elucidates the geographical differences within a country.
      The incidence of seropositive MG did not vary significantly between the regions.
      Mid-Norway tended to have a higher incidence, and North tended to have a lower
      incidence.

PMID- 22581534
TI  - Psychometric evaluation of the myasthenia gravis composite using Rasch analysis.
AB  - INTRODUCTION: The MG Composite (MGC) is a validated outcome measure of the
      clinical manifestations of myasthenia gravis. METHODS: We performed Rasch
      analyses of the MGC to investigate additional properties, including its
      unidimensionality and the appropriateness of the weights assigned to the response
      categories for the MGC items. RESULTS: The fit statistics indicated that the 10
      items belong together and can be summated for a total score. There was an overall
      absence of item order distortion between response categories. The Rasch model's
      expected category response values were compatible with item weights previously
      assigned. CONCLUSIONS: Our analysis suggests that: (1) the score can be summated
      to estimate an overall disease severity score; (2) the response options of the 10
      items are not significantly distorted; and (3) the assigned weights of the
      response options are appropriate.

PMID- 22581535
TI  - Glial S100B is elevated in serum across the spectrum of West Nile virus
      infection.
AB  - INTRODUCTION: We previously reported that protein biomarkers of neuronal death
      and glial pathology were elevated in the cerebrospinal fluid of patients with
      West Nile virus (WNV) infection, including WNV fever. Therefore, we hypothesized
      that the glial biomarker S100B would also be elevated in serum across the
      spectrum of WNV disease. METHODS: Serum levels of S100B were measured by enzyme
      linked immunoassay (ELISA) in 90 WNV patients (35 with neuroinvasive disease and
      55 with WNV fever) and compared with 34 healthy controls. RESULTS: Serum S100B
      was significantly higher in patients (median 0.17 ng/ml) than in controls (0.09
      ng/ml, P < 0.0001). Serum S100B was elevated in 16 cases (46%) with neuroinvasive
      disease and in 19 cases (35%) with WNV fever. CONCLUSIONS: The increase in serum
      S100B reaffirms pathological changes across the spectrum of WNV disease. The
      elevated S100B in over one third of WNV fever cases implies that neuroinvasion
      occurs in a much greater proportion of patients than anticipated by clinical and
      epidemiological data.

PMID- 22581536
TI  - New motor outcome function measures in evaluation of late-onset Pompe disease
      before and after enzyme replacement therapy.
AB  - INTRODUCTION: The clinical course of late-onset Pompe disease is heterogeneous,
      and new clinical outcome measures are needed to evaluate enzyme replacement
      therapy (ERT). METHODS: We correlated the 6-Minute Walk Test (6MWT), Walton and
      Gardner-Medwin (WGM) score, and GSGC (Gait, Stairs, Gower, Chair) scores in 40
      patients. RESULTS: At baseline, the GSGC score correlated with both WGM (P <
      0.001, n = 33) and 6MWT (P < 0.001, n = 26). After 1 year of ERT, we observed a
      significant change in gait, stairs and chair performance on the GSGC scale. The
      6MWT significantly increased from 319 to 371 meters in 32 patients, and the WGM
      score was reduced. CONCLUSIONS: GSGC is a group of functional tests that requires
      only a few minutes to perform, therefore, this score might be a good indicator to
      be used in future studies.

PMID- 22581537
TI  - Prediction of time-to-exhaustion in the first dorsal interosseous muscle from
      early changes in surface electromyography parameters.
AB  - INTRODUCTION: In this study we evaluated the precision of the time-to-exhaustion
      (T(lim)) prediction from the early changes in surface electromyography (sEMG) of
      the first dorsal interosseous muscle. METHODS: Thirty subjects performed an index
      finger isometric abduction at 35% of maximal voluntary contraction (MVC) until
      exhaustion. Ten participants performed the same exercise at 50% MVC 1 week later.
      Changes in sEMG parameters across time were modeled using the area-ratio and the
      linear regression slope. T(lim) was plotted as a function of each of these
      indices of change, and the coefficient of determination (R(2)) was determined.
      RESULTS: Null to moderate R(2) (0.22 and 0.56 at 35% and 50% MVC, respectively)
      values were calculated. The best T(lim) estimation led to a high prediction error
      (21.6 +/- 15.0% of T(lim) for the 50% MVC task). CONCLUSIONS: Although the
      prediction of time-to-exhaustion is an appealing research topic, these results
      suggest that it cannot be done solely from sEMG.

PMID- 22581538
TI  - Effect of stimulation intensity on assessment of voluntary activation.
AB  - INTRODUCTION: The interpolated twitch technique is often used to assess voluntary
      activation (VA) of skeletal muscles. We investigated VA and the voluntary torque
      superimposed torque relationship using either supramaximal nerve stimulation or
      better tolerated submaximal muscle stimulation, which is often used with
      patients. METHODS: Thirteen healthy subjects performed maximal and submaximal
      isometric knee extensions with superimposed maximal or submaximal doublets (100
      Hz). RESULTS: Superimposed torque relative to potentiated resting doublets was
      smaller with maximal nerve than with submaximal muscle stimulation. Maximal VA
      was 87 +/- 7% and 93 +/- 5% for submaximal muscle and maximal nerve stimulation,
      respectively. The individual voluntary torque-superimposed torque relationships
      were more linear for submaximal muscle stimulation, possibly leading to less
      overestimation of VA. CONCLUSIONS: Submaximal muscle stimulation can be used to
      estimate VA in the knee extensors. It is less painful, and overestimation of VA
      may be less compared with maximal nerve stimulation.

PMID- 22581539
TI  - Using submaximal contractions to predict the maximum force-generating ability of
      muscles.
AB  - INTRODUCTION: Muscle weakness can be caused by decreases in either the maximum
      force-generating ability of a muscle (MFGA) or neural drive from the nervous
      system (e.g., after a stroke). Presently, there is no agreed-upon practical
      method for calculating the MFGA in individuals with central nervous system
      pathology. The purpose of this study was to identify the best method for
      determining MFGA. METHODS: The predicted and estimated MFGA of the muscles of 23
      non-neurologically impaired subjects (13 males, 21.9 +/- 1.9 years) were compared
      using the burst superimposition, twitch interpolation, doublet interpolation,
      twitch-to-tetanus ratio, and the adjusted burst superimposition methods. RESULTS:
      The adjusted burst superimposition test was the most accurate predictor of MFGA.
      CONCLUSIONS: Further testing is needed to validate the use of the adjusted burst
      superimposition test in a neurologically impaired population.

PMID- 22581540
TI  - Unexpected neuroimaging abnormalities in patients with apparent C8 radiculopathy:
      broadening the clinical spectrum.
AB  - INTRODUCTION: C8-root impingement by C7/T1 lesions on neuroimaging studies is not
      consistently observed in C8 radiculopathy. We hypothesized that C7 or T1 root
      lesions (with a pre- or postfixed plexus) or cervical myelopathy might explain
      some "C8 radiculopathies" without C8 root compression. METHODS: Retrospective
      analysis of cervical neuroimaging in 31 consecutive patients with EMG-confirmed
      C8 radiculopathy. RESULTS: Five patients (16%) had C8-root compression at C7/T1.
      Of those without C8-root compression, 5 (16%) had C7-root compression at C6/7,
      one (3%) had T1-root compression at T1/T2, 7 (23%) had cervical cord compression
      at or above the C6/7 level, 4 (13%) had intramedullary cervical lesions, and 9
      (29%) had mild or nonspecific findings. CONCLUSIONS: C8 radiculopathy without C8
      root compression may be due to C7-root compression in the setting of a "prefixed"
      brachial plexus, upper cervical cord compression with vascular compromise of the
      distal cervical spinal cord ("myelopathic hand"), or intramedullary cervical cord
      lesions.

PMID- 22581541
TI  - Clinical and laboratory features of neuropathies with serum IgM binding to TS
      HDS.
AB  - INTRODUCTION: In this investigation we studied clinical and laboratory features
      of polyneuropathies in patients with serum IgM binding to the trisulfated
      disaccharide IdoA2S-GlcNS-6S (TS-HDS). METHODS: We retrospectively compared 58
      patients with selective IgM binding to TS-HDS to 41 consecutive patients with
      polyneuropathies without TS-HDS binding. RESULTS: Patients with IgM vs. TS-HDS
      commonly had distal, sensory, axonal neuropathies. Weakness was associated with
      IgM M-proteins. Hand pain and serum IgM M-proteins were more common than in
      control neuropathy patients. TS-HDS antibody binding was often selectively kappa
      class. Biopsies showed capillary pathology with thickened basal lamina and C5b9
      complement deposition. IgM in sera with TS-HDS antibodies often bound to
      capillaries. CONCLUSIONS: Serum IgM binding to TS-HDS is associated with painful,
      sensory > motor, polyneuropathies with an increased frequency of persistent hand
      discomfort, serum IgM M-proteins, and capillary pathology. Serum IgM binding to
      TS-HDS suggests a possible immune etiology underlying some otherwise idiopathic
      sensory polyneuropathies.

PMID- 22581542
TI  - Surface electromyography features in manual workers affected by carpal tunnel
      syndrome.
AB  - INTRODUCTION: Alterations in surface electromyographic (sEMG) signals of the
      abductor pollicis brevis muscle were evaluated in 24 non-manual workers and 40
      manual workers (25 asymptomatic and 15 reporting CTS symptoms). METHODS: The
      initial value (IV) and the normalized rate of change (NRC) of average rectified
      value (ARV), mean frequency of the power spectrum (MNF), and muscle fiber
      conduction velocity (MFCV) were calculated during contractions at 20% and 50% of
      maximal voluntary contraction (MVC). Neuromuscular efficiency (NME) and kurtosis
      of the sEMG amplitude distribution were estimated. RESULTS: With respect to
      controls, manual workers showed higher NME, lower ARV IV, and reduced myoelectric
      manifestations of fatigue (lower MNF NRC for both contraction levels, and lower
      MFCV NRC at 50% MVC). Kurtosis at 20% MVC showed higher values in symptomatic
      manual workers than in the other two groups. CONCLUSIONS: Kurtosis seems to be a
      promising parameter for use in monitoring individuals who develop CTS.

PMID- 22581543
TI  - Neuropathic pain in post-burn hypertrophic scars: a psychophysical and
      neurophysiological study.
AB  - INTRODUCTION: Pain complicates hypertrophic post-burn pathologic scars (PPS)
      METHODS: To investigate the possible neuropathic origin of pain, 13 patients with
      painful PPS involving at least 1 hand underwent clinical examination, including
      the Douleur Neuropathique en 4 questions (DN4) questionnaire; median, ulnar, and
      radial nerve conduction studies (NCS); cold- (CDT) and heat-induced pain
      threshold evaluation by quantitative sensory testing; and cutaneous silent period
      (CSP) testing of the abductor pollicis brevis. Controls included 9 patients with
      non-painful PPS, 52 healthy subjects, and 28 patients with carpal tunnel syndrome
      (CTS). RESULTS: All patients with painful PPS had possible neuropathic pain (DN4
      score >=4). NCS signs of CTS were similarly present in PPS subjects with or
      without pain. Hands with painful PPS had lower CDT and CSP duration, more
      frequent cold- and heat-pain hypesthesia, and more thermal allodynia than
      controls. CONCLUSIONS: In PPS, possible neuropathic pain is associated with
      psychophysical and neurophysiological abnormalities suggestive of small-fiber
      damage.

PMID- 22581544
TI  - The electrodiagnostic sensitivity of proximal lower extremity muscles in the
      diagnosis of L5 radiculopathy.
AB  - The aim of this study was to assess the electrodiagnostic (EDx) sensitivity of
      proximal lower extremity muscles, including tensor fascia lata (TFL) and gluteus
      medius (GMED), in the diagnosis of L5 radiculopathy.Eleven EDx recordings with L5
      radiculopathy were collected. The motor unit action potentials were assessed for
      morphology, stability, and firing characteristics. A descriptive analysis was
      performed. In proximal L5-supplied muscles, 4 of 11 recordings were abnormal in
      TFL only, with normal GMED; 4 of 11 recordings had similar findings in both
      muscles; 2 of 11 had abnormal findings in both muscles, but TFL had more
      noticeable findings; and 1 had abnormal findings in both muscles, but GMED
      findings were more noticeable. No patient had abnormalities limited to GMED. TFL
      was more sensitive than GMED in detecting L5 radiculopathy. Knowing which muscles
      are more likely to show abnormalities can improve the efficiency of EMG and
      reduce patient discomfort. Muscle Nerve 45: 891-893, 2012.

PMID- 22581545
TI  - Prognosis of acute compressive radial neuropathy.
AB  - INTRODUCTION: Small published case series suggest that compressive radial
      neuropathy is often a self-limited phenomenon with a favorable prognosis. Due to
      paucity of data, we sought to clearly define prognosis. METHODS: To define
      clinical and electrodiagnostic features in this condition, we retrospectively
      reviewed consecutive cases of compressive radial neuropathy confirmed using
      electrodiagnostic studies at a large tertiary center over a 10-year period.
      RESULTS: A total of 51 patients (26 men, 25 women, mean age 46 years +/- 15;
      range, 19-83 years) with compressive radial neuropathy were identified and
      reviewed. All patients in whom clinical follow-up was available (23 [45%] of the
      51 patients identified) experienced complete recovery. Mean duration from onset
      to resolution of symptoms was 3.4 months. CONCLUSIONS: Our results support a good
      prognosis in essentially all patients with acute compressive radial neuropathies.
      This report provides valuable information to assist in counseling patients who
      may present with profound clinical deficits.

PMID- 22581546
TI  - Does the presence of the palmaris longus tendon influence median nerve function?
AB  - INTRODUCTION: The objective of this study was to determine if the presence or
      absence of a palmaris longis tendon influenced the function of the median nerve
      across the wrist. The primary hypothesis was that the presence of a palmaris
      longus tendon would be associated with more median nerve entrapment at the wrist.
      METHODS: This was a cross-sectional study. Subjects were recruited at a screening
      of dental professionals. The median and ulnar sensory nerve latencies across the
      wrist (relative prolongation of the median compared with the ulnar) and the
      presence or absence of the palmaris longus tendon were the primary outcome
      measures. RESULTS: A total of 462 subjects were recruited into the study of which
      16.2% lacked a palmaris longus tendon. There was no difference in the median
      nerve function or the percentage with a 0.5 ms prolongation of the median sensory
      latency when comparing subjects with and without a palmaris longus tendon.
      CONCLUSIONS: The presence of a palmaris longus tendon does not influence the
      median nerve function across the wrist.

PMID- 22581547
TI  - Myotonia associated with caveolin-3 mutation.
AB  - INTRODUCTION: Caveolin-3 is a major component of the caveolae in skeletal and
      cardiac muscle. Mutations in the caveolin-3 gene (CAV3) lead to a spectrum of
      clinical phenotypes including limb-girdle muscular dystrophy 1C, distal myopathy,
      rippling muscle disease, isolated hyperCKemia, and cardiomyopathy. CASE REPORT: A
      24-year-old man with myalgia, muscle stiffness, and fatigue has normal strength
      and prominent myotonic discharges in the gastrocnemius. He also has epilepsy. He
      harbors a heterozygous CAV3 mutation, p.V57M. He has no mutations in CLCN1 and
      SCN4A, and he had normal genetic testing for myotonic dystrophy type 1 and type
      2. CONCLUSIONS: Mutations in CAV3, and in particular p.V57M in CAV3, previously
      reported in isolated familial hyperCKemia, can be associated with electrical
      myotonia.

PMID- 22581548
TI  - Subacute brachial diplegia associated with West Nile virus myelitis.
AB  - INTRODUCTION: Brachial diplegia is a clinical term used to describe weakness
      restricted to the upper extremities. We report a case of brachial diplegia
      associated with West Nile virus infection. METHODS: A 48-year-old man developed
      severe painless bilateral upper extremity weakness within a few weeks of a flu
      like illness. RESULTS: Clinical examination revealed marked periscapular,
      shoulder girdle, and humeral muscle atrophy and bilateral scapular winging, with
      near symmetrical bilateral hypotonic upper extremity weakness. This was
      associated with clinical signs of an encephalomyelopathy without cognitive or
      sensory deficits. Electrophysiological studies demonstrated a subacute disorder
      of motor neurons, their axons or both, involving the cervical and thoracic
      myotomes, with ongoing denervation. Serological studies confirmed recent West
      Nile virus (WNV) infection. Gradual improvement occurred following conservative
      supportive therapies. CONCLUSIONS: Progressive brachial diplegia is a rare
      neuromuscular presentation of WNV neuroinvasive disease. This case report adds to
      the clinical spectrum of WNV-induced neurologic sequelae.

PMID- 22581549
TI  - Myopathy in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.
AB  - INTRODUCTION: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy
      (APECED) is a rare autosomal recessive disorder caused by monogenic mutations in
      the autoimmune regulator (AIRE) gene. No attention has been paid to muscle
      manifestations in this disorder. We aimed to uncover whether progressive myopathy
      is a component of this disorder. METHODS: A case description and literature
      search for APECED cases presenting with myopathy and analysis of AIRE gene
      expression in biopsied muscles from 4 healthy volunteers and the patient by
      reverse transcriptase polymerase chain reaction. RESULTS: A 52-year-old woman
      with APECED caused by AIRE gene mutations developed progressive myopathy
      involving proximal limb and paraspinal muscles. Muscle biopsy specimens showed
      myopathic changes without inflammatory cell infiltrate. We detected AIRE gene
      expression in all muscle tissues examined. An extensive literature search
      uncovered 5 cases of APECED with myopathy, all of whom had similar features.
      CONCLUSIONS: Progressive myopathy involvement could be a hitherto unknown
      manifestation of APECED.

PMID- 22581550
TI  - Recommendations for myasthenia gravis clinical trials.
AB  - The recommendations for clinical research standards published in 2000 by a task
      force of the Medical Scientific Advisory Board (MSAB) of the Myasthenia Gravis
      Foundation of America (MGFA) were largely successful in introducing greater
      uniformity in the recording and reporting of MG clinical trials. Recognizing that
      changes in clinical trial design and implementation may increase the likelihood
      that new therapies are developed for MG, the MGFA MSAB Task Force here presents
      updated recommendations for the design and implementation of clinical trials in
      MG, including (a) the use of a quantitative measure, such as the MG-Composite,
      that is weighted for clinical significance and incorporates patient reported
      outcomes; (b) consideration of nontrial strategies; and (c) development of
      biomarkers that support mechanistic studies of pharmacotherapies. The hope is
      that these updated task force recommendations will expedite the development and
      acceptance of more effective and less noxious therapies for MG.

PMID- 22581551
TI  - Amyloid polyneuropathy following domino liver transplantation.

PMID- 22581552
TI  - The p.Arg416Cys mutation in SPG3a gene associated with a pure form of spastic
      paraplegia.

PMID- 22581553
TI  - Sonographic features in hereditary neuropathy with liability to pressure palsies.

PMID- 22581555
TI  - High-resolution ultrasonography in the assessment of meralgia paresthetica: some
      clarifications are needed.

PMID- 22581563
TI  - Lineage tracing of the endoderm during oral development.
AB  - BACKGROUND: The contribution of the endoderm to the oral tissues of the head has
      been debated for many years. With the arrival of Cre/LoxP technology endoderm
      progenitor cells can now be genetically labeled and tissues derived from the
      endoderm traced. Using Sox17-2A-iCre/Rosa26 reporter mice we have followed the
      fate of the endoderm in the teeth, glands, and taste papillae of the oral cavity.
      RESULTS: No contribution of the endoderm was observed at any stage of tooth
      development, or in development of the major salivary glands, in the reporter
      mouse during development. In contrast, the minor mucous glands of the tongue were
      found to be of endodermal origin, along with the circumvallate papilla and
      foliate papillae. The mucous minor salivary glands of the palate, however, were
      of mixed ectodermal and endodermal origin. CONCLUSIONS: In contrast to urodele
      studies, the epithelium of murine teeth is derived solely from the ectoderm. The
      border between the ectoderm- and endoderm-derived epithelium may play a role in
      determining the position of the lingual glands and taste buds, and may explain
      differences observed between taste buds in the anterior and posterior part of the
      tongue.

PMID- 22581564
TI  - Use of abatacept in rheumatoid arthritis.
AB  - Abatacept (CTLA-Ig), a modulator of T-lymphocyte activation, has been approved by
      the Swiss health regulatory agency Swissmedic for the treatment of active
      rheumatoid arthritis (RA). This article summarises the key trial findings for
      this biologic agent in RA in different situations such as early erosive
      rheumatoid arthritis (RA), biologic-naive RA, RA before and after the use of
      methotrexate or TNF-inhibitors and includes safety information from these trials.
      Based on these data, recommendations for clinical practice in Switzerland are
      made by a panel of experts.

PMID- 22581566
TI  - Safety and immediate effect of noninvasive transcranial pulsed current
      stimulation on gait and balance in Parkinson disease.
AB  - BACKGROUND: Noninvasive electrical stimulation of the brain (ESB) is being
      investigated as a valued intervention to enhance motor performance. OBJECTIVE: To
      ascertain the safety and ability of transcranial pulsed current stimulation
      (tPCS) to modulate variables of protective stepping and gait of individuals with
      Parkinson's disease. METHOD: Ten patients participated in a pilot study. During
      the first session, a tPCS delivered current for 20 minutes via a positive
      electrode placed over the primary motor area (M1). In week 2, participants walked
      for 20 minutes on a treadmill. In week 3, tPCS and treadmill for 20 minutes were
      combined. Pre-testing and post-testing of gait and protective stepping were
      administered, comparing post-intervention (tPCS alone, treadmill alone, tPCS +
      treadmill) with pre-intervention data. The 3 interventions were compared by
      calculating the difference between post-intervention and pre-intervention data. A
      significance level of P < .05 was adopted. RESULTS: Stride length increased from
      102.1 +/- 24.4 to 111.2 +/- 22.1 cm, and gait velocity increased from 0.90 +/-
      0.23 to 0.985 +/- 0.19 m/s after tPCS. Treadmill or treadmill + tPCS did not
      result in changes in the studied gait parameters. The tPCS session increased gait
      velocity and stride length significantly compared with treadmill or tPCS +
      treadmill. Overall, the number of steps needed to recover balance decreased after
      tPCS and tPCS + treadmill. CONCLUSION: Noninvasive tPCS over the primary motor
      cortex had no adverse effects on those with long-standing Parkinson's disease and
      may lead to acute improvement of gait and balance recovery.

PMID- 22581567
TI  - Seeing the same thing differently: mechanisms that contribute to assessor
      differences in directly-observed performance assessments.
AB  - Assessors' scores in performance assessments are known to be highly variable.
      Attempted improvements through training or rating format have achieved minimal
      gains. The mechanisms that contribute to variability in assessors' scoring remain
      unclear. This study investigated these mechanisms. We used a qualitative approach
      to study assessors' judgements whilst they observed common simulated videoed
      performances of junior doctors obtaining clinical histories. Assessors commented
      concurrently and retrospectively on performances, provided scores and follow-up
      interviews. Data were analysed using principles of grounded theory. We developed
      three themes that help to explain how variability arises: Differential Salience
      assessors paid attention to (or valued) different aspects of the performances to
      different degrees; Criterion Uncertainty-assessors' criteria were differently
      constructed, uncertain, and were influenced by recent exemplars; Information
      Integration-assessors described the valence of their comments in their own unique
      narrative terms, usually forming global impressions. Our results (whilst not
      precluding the operation of established biases) describe mechanisms by which
      assessors' judgements become meaningfully-different or unique. Our results have
      theoretical relevance to understanding the formative educational messages that
      performance assessments provide. They give insight relevant to assessor training,
      assessors' ability to be observationally "objective" and to the educational value
      of narrative comments (in contrast to numerical ratings). 

PMID- 22581565
TI  - Systems pharmacology, pharmacogenetics, and clinical trial design in network
      medicine.
AB  - The rapidly growing disciplines of systems biology and network science are now
      poised to meet the fields of clinical medicine and pharmacology. Principles of
      systems pharmacology can be applied to drug design and, ultimately, testing in
      human clinical trials. Rather than focusing exclusively on single drug targets,
      systems pharmacology examines the holistic response of a phenotype-dependent
      pathway or pathways to drug perturbation. Knowledge of individual pharmacogenetic
      profiles further modulates the responses to these drug perturbations, moving the
      field toward more individualized ('personalized') drug development. The speed
      with which the information required to assess these system responses and their
      genomic underpinnings is changing and the importance of identifying the optimal
      drug or drug combinations for maximal benefit and minimal risk require that
      clinical trial design strategies be adaptable. In this paper, we review the
      tenets of adaptive clinical trial design as they may apply to an era of expanding
      knowledge of systems pharmacology and pharmacogenomics, and clinical trail design
      in network medicine.

PMID- 22581568
TI  - Feedback sandwiches affect perceptions but not performance.
AB  - The feedback sandwich technique-make positive comments; provide critique; end
      with positive comments-is commonly recommended to feedback givers despite scant
      evidence of its efficacy. These two studies (N = 20; N = 350) of written peer
      feedback with third-year medical students on clinical patient note-writing
      assignments indicate that students think feedback sandwiches positively impact
      subsequent performance when there is no evidence that they do. The effort
      necessary to produce feedback sandwiches and students' unwarranted confidence in
      their performance impact have implications for teaching about how to give
      feedback. 

PMID- 22581569
TI  - Familial distal monosomy 3p26.3-pter with trisomy 4q32.2-qter, presenting with
      progressive ataxia, intellectual disability, and dysmorphic features.
AB  - We present a boy diagnosed with partial 3p monosomy and partial 4q trisomy. The
      patient was 9 years of age with intellectual disability, dysmorphic features, and
      ataxia. A family history and medical evaluation showed that the father manifested
      similar facial dysmorphic features, intellectual disability, quadriparesis, and
      progressive cerebrospinal ataxia. The chromosomal aberration found in the proband
      was inherited from his father who was found to have a balanced reciprocal
      translocation of chromosomes 3p and 4q, which was in turn inherited from the
      paternal grandfather. The final cytogenetic diagnosis according to microarray was
      46,XY,der(3)t(3;4)(p26.1;q32.2)arr 3p26.1(39,066
      5,363,502)x1,4q32.2q35.2(162,555,236-191,173,881)x3. We describe the cytogenetic
      investigations that led to the identification of the breakpoints. In addition, we
      present an overview of the clinical features found in patients with partial 3p
      monosomies and partial 4q trisomies as reported in the literature.

PMID- 22581570
TI  - Characterization of the microbial diversity in production waters of mesothermic
      and geothermic Tunisian oilfields.
AB  - The microbial diversity of production waters of five Tunisian oilfields was
      investigated using Single Strand Conformation Polymorphism (SSCP) technique
      followed by cloning-sequencing. Dynamics of bacterial populations in production
      waters collected from four wellheads were also evaluated. For all production
      water samples collected, DNA from Archaea and Eucarya was not sufficiently
      abundant to permit detection rRNA genes from these groups by PCR-SSCP. In
      contrast, the bacterial rRNA genes were detected in all samples, except for
      samples from DOULEB12 and RAMOURA wells. SSCP profiles attested that two of the
      studied geothermic wells (ASHTART47 and ASHTART48) had shown a clear change over
      time, whereas a stable diversity was found with the mesophilic DOULEB well (DL3).
      PCR amplification of rRNA genes was unsuccessful with samples from DOULEB (DL12)
      at all three sampling time. The bacterial diversity present in production waters
      collected from pipelines of SERCINA and LITAYEM oilfields was high, while
      production waters collected from wellheads (ASHTART and DOULEB) exhibited lower
      diversity. The partial study of the biodiversity showed a dominance of uncultured
      bacteria and Pseudomonas genus (class of the Gammaproteobacteria) in three of the
      studied oilfields (ASHTART47, ASHTART48 and DOULEB3). However, for LITAYEM
      oilfield, a significant dominance of 5 phyla (Proteobacteria, Thermotogae,
      Firmicutes, Synergistetes, Bacteroidetes) was shown. Our study gives a real
      picture of the microbiology of some Tunisian oilfield production waters and shows
      that some of the sequenced bacterial clones have a great similarity to previous
      sequenced clones described from other oilfields all over the world, indicating
      that these ecosystems harbour specific microbial communities. These findings can
      be considered as an indirect indication of the indigenous origin of these clones.

PMID- 22581571
TI  - A sinister cause of back pain in a young man.

PMID- 22581572
TI  - Familial hypercholesterolaemia.

PMID- 22581573
TI  - US hospitals face shortages of anaesthesia drug as supplies are diverted for
      executions.

PMID- 22581574
TI  - Better training is needed to deal with increasing multimorbidity.

PMID- 22581575
TI  - Minsters use veto to stop publication of register of risks posed by NHS changes.

PMID- 22581576
TI  - Abbott pays $1.6bn for promoting off label use of valproic acid.

PMID- 22581577
TI  - Coexpression of molecular chaperone enhances activity and export of
      organophosphorus hydrolase in Escherichia coli.
AB  - Periplasmic secretion has been used in attempts to construct an efficient whole
      cell biocatalyst with greatly reduced diffusion limitations. Previously, we
      developed recombinant Escherichia coli that express organophosphorus hydrolase
      (OPH) in the periplasmic space using the twin-arginine translocation (Tat)
      pathway to degrade environmental toxic organophosphate compounds. This system has
      the advantage of secreting protein into the periplasm after folding in the
      cytoplasm. However, when OPH was expressed with a Tat signal sequence in E. coli,
      we found that the predominant OPH was an insoluble premature form in the
      cytoplasm, and thus, the whole-cell OPH activity was significantly lower than its
      cell lysate activity. In this work, we, for the first time, used a molecular
      chaperone coexpression strategy to enhance whole-cell OPH activity by improving
      the periplasmic translocation of soluble OPH. We found that the effect of GroEL
      GroES (GroEL/ES) assistance on the periplasmic localization of OPH was secretory
      pathway dependent. We observed a significant increase in the amount of soluble
      mature OPH when cytoplasmic GroEL/ES was expressed; this increase in the amount
      of mature OPH might be due to enhanced OPH folding in the cytoplasm. Importantly,
      the whole-cell OPH activity of the chaperone-coexpressing cells was ~5.5-fold
      greater at 12 h after induction than that of cells that did not express the
      chaperone as a result of significant Tat-based periplasmic translocation of OPH
      in the chaperone-coexpressing cells. Collectively, these data suggest that
      molecular chaperones significantly enhance the whole-cell activity of periplasmic
      OPH-secreting cells, yielding an effective whole-cell biocatalyst system with
      highly reduced diffusion limitations.

PMID- 22581578
TI  - An efficient protocol for isolating melanised chaetothyrialean anamorphic fungi
      associated with plant-ants.
AB  - Because of their ecological characteristics, slow growth rates and the presence
      of contaminants, Chaetothyriales fungi associated with structures built by
      tropical plant-ants can be difficult to isolate with standard procedures. Here,
      we describe an easy-to-use protocol for obtaining pure cultures by using cotton
      as a first substrate. We have further found by means of fluorescent stains that
      nuclei concentrate either in young hyphae or in the tips of the hyphae.

PMID- 22581579
TI  - Accuracy of self-reported weight in a high risk geriatric population in the
      emergency department.
AB  - QUESTIONS UNDER STUDY/PRINCIPLES: Weight is important information in the
      emergency department (ED). Weight loss leads to an increase of mortality and is
      suggestive of morbidity. Correct weight is important for dosing of drugs to avoid
      toxicity and lack of effectiveness. Objective body weight measurement is often
      not possible in the emergency department. Especially in elderly ED patients,
      acute disease might have an impact on weight reporting. The objective of this
      study was to determine whether body weight reported by elderly patients
      presenting to the ED with non-specific symptoms is accurate. METHODS: In 233
      patients, measured weight was detected within patients' medical record and was
      compared to reported weight at presentation in the ED. RESULTS: The median age of
      the observed population was 74 years (IQR 72, 86). Comparison between estimated
      and measured weight showed a good agreement between the two measures (Pearson's
      correlation coefficient r = 0.94). The mean difference between estimated and
      measured weight was small (+0.1 kg) whereas the range of the estimation error was
      between -10.9 and 11.1 kg. Age had no influence on the accuracy to predict the
      measured weight. Also, the correlation did not differ in patients with and
      without acute morbidity or between men and women. CONCLUSIONS: Neither old age
      nor acute disease status impaired the strong correlation of reported and measured
      weight. Therefore, self reported weight can be used as approximation for real
      body weight in elderly ED patients presenting with non-specific complaints.

PMID- 22581580
TI  - The face signature of fibrodysplasia ossificans progressiva.
AB  - Fibrodysplasia ossificans progressiva (FOP) causes extensive heterotopic bone
      formation due to heterozygous mutations in the glycine-serine activation domain
      of ACVR1 (ALK2), a bone morphogenetic protein type I receptor. Anecdotal
      observations of facial similarity have been made by clinicians and parents, but
      no objective quantitative analysis of the faces of FOP patients has ever been
      undertaken. We delineated the common facial characteristics of 55 individuals
      with molecularly confirmed FOP by analyzing their face signature (face shape
      difference normalized against age and sex matched controls) and associated face
      signature graphs (with face signatures as vertices and adjacency corresponding to
      greatest similarity). Our analysis identified 10 affected individuals whose face
      signature is more homogeneous than others with FOP. This distinct subgroup showed
      the previously identified reduced mandible as well as newly identified features:
      underdevelopment of the upper orbit/supra-orbital ridge; infra-orbital
      prominence; and, low-set ears. These findings strongly suggest that the canonical
      FOP mutation variably affects the postnatal morphogenesis of the normotopic
      cranial skeleton in the upper midface and mandible and may have important
      diagnostic and functional implications.

PMID- 22581581
TI  - Renal artery intervention using a virtual 4.5-Fr guiding catheter.
AB  - A 6.5-Fr guiding catheter (Parent Plus 45, Medikit, Tokyo, Japan), composed of a
      hydrophilic sheathless guiding catheter and a dilator, has recently been
      developed for the treatment of renal artery stenosis. Because of its unique
      sheathless configuration, its outer diameter is comparable to that of a
      conventional 4.5-Fr introducer sheath, with the inner diameter being close in
      size to a 6.5-Fr guiding catheter. These features allow this sheathless system to
      be used as the sole guiding catheter while the arterial damage at the puncture
      site remains equivalent to that of a 4.5-Fr introducer sheath. We thus call this
      novel sheathless guiding catheter a virtual 4.5-Fr system. To demonstrate the
      potential of this virtual 4.5-Fr system, we report a case of renal artery
      stenosis successfully treated via the transradial route. This virtual 4.5-Fr
      system may become a viable alternative to conventional guiding catheters, and
      provide a favorable impact upon vascular access complications and patient
      morbidity.

PMID- 22581582
TI  - Facile preparation of indoles and 1,2-benzothiazine 1,1-dioxides: nucleophilic
      addition of sulfonamides to bromoacetylenes and subsequent palladium-catalyzed
      cyclization.
AB  - Bromine as a double agent: The bromine atom in 1-bromo-1-alkynes works as an
      electron-withdrawing group to effect the nucleophilic addition of sulfonamides.
      It again plays a pivotal role in the palladium-catalyzed cyclization of the
      resultant (Z)-2-(sulfonylamino)-1-bromoalkenes into nitrogen heterocycles (see
      scheme).

PMID- 22581583
TI  - Neurotrophin therapy improves recovery of the neuromuscular continence mechanism
      following simulated birth injury in rats.
AB  - AIMS: Stress urinary incontinence (SUI) affects women both acutely and
      chronically after vaginal delivery. Current SUI treatments assume the
      neuromuscular continence mechanism, comprised of the pudendal nerve (PN) and
      external urethral sphincter (EUS), is either intact or irreparable. This study
      investigated the ability of neurotrophin therapy to facilitate recovery of the
      neuromuscular continence mechanism. METHODS: Virgin, Sprague Dawley rats received
      simulated childbirth injury or sham injury and treatment with continuous infusion
      of brain-derived neurotrophic factor (BDNF) or saline placebo to the site of PN
      injury. Continence was assessed by leak point pressure (LPP) and EUS
      electromyography (EMG) 14 and 21 days after injury. Structural recovery was
      assessed histologically. Molecular assessment of the muscular and
      neuroregenerative response was determined via measurement of EUS BDNF and PN
      beta(II) -tubulin expression respectively, 4, 8, and 12 days after injury.
      RESULTS: Following injury, LPP was significantly reduced with saline compared to
      either BDNF treatment or sham injury. Similarly, compared to sham injury, resting
      EUS EMG amplitude and firing rate, as well as amplitude during LPP were
      significantly reduced with saline but not BDNF treatment. Histology confirmed
      improved EUS recovery with BDNF treatment. EUS BDNF and PN beta(II)-tubulin
      expression demonstrated that BDNF treatment improved the neurogenerative response
      and may facilitate sphincteric recovery. CONCLUSIONS: Continuous targeted
      neurotrophin therapy accelerates continence recovery after simulated childbirth
      injury likely through stimulating neuroregeneration and facilitating EUS recovery
      and re-innervation. Neurotrophins or other therapies targeting neuromuscular
      regeneration may be useful for treating SUI related to failure of the
      neuromuscular continence mechanism.

PMID- 22581584
TI  - ADAM10 overexpression confers resistance to doxorubicin-induced apoptosis in
      hepatocellular carcinoma.
AB  - Chemoresistance represents a major obstacle to successful treatment of
      hepatocellular carcinoma (HCC). A disintegrin and metalloproteinase 10 (ADAM10)
      is known to be frequently upregulated in many cancers. We aimed to determine the
      biological function of ADAM10 in the chemoresistance of HCC cells. Overexpression
      of ADAM10 in three HCC cell lines (HepG2, Hep3B, and Huh7) conferred protection
      against doxorubicin-induced apoptosis, as determined by Annexin V staining.
      Western blot analysis revealed that ADAM10-overexpressing cells had a
      significantly lower amount of cleaved caspase-3 and an elevated expression of
      myeloid cell leukemia-1 (Mcl-1), a prosurvival member of the Bcl-2 family.
      Conversely, RNA interference-mediated silencing of endogenous ADAM10 potentiated
      doxorubicin-induced apoptosis in HepG2 and Hep3B cells, which was coupled with
      increased cleavage of caspase-3 and decreased expression of Mcl-1. Ectopic
      expression of ADAM10 resulted in a marked increase in the phosphorylation of
      phosphatidylinositol 3-kinase (PI3-K) and Akt. Most interestingly, the
      pretreatment with the PI3-K inhibitor LY294002 significantly enhanced doxorubicin
      induced apoptosis and diminished the Mcl-1 expression in ADAM10-overexpressing
      Huh7 cells. Our data provide evidence that ADAM10 plays an important role in
      modulating the chemosensitivity of HCC cells, which, at least partially, involves
      the activation of the PI3-K/Akt pathway. ADAM10 may be a promising target for the
      improvement of chemotherapeutic efficacy in HCC.

PMID- 22581586
TI  - Instrumental activities of daily living: more than just piano-playing?

PMID- 22581585
TI  - Life-sustaining treatment decisions in the ICU for patients with ESLD: a
      prospective investigation.
AB  - We conducted a prospective study in the ICU of life-sustaining treatment and
      comfort care decisions over time in patients with end-stage liver disease (ESLD)
      from the perspectives of patients, family members, and healthcare professionals.
      Six patients with ESLD, 19 family members, and 122 professionals participated.
      The overarching theme describing the decision-making process was "on the train."
      Four sub-themes positioned patients and family members as passengers with limited
      control, unable to fully understand the decision-making process. Findings suggest
      that including patients and family members in non-immediate life-saving decisions
      and verifying early on their understanding may help to improve the decision
      making process.

PMID- 22581587
TI  - Characterization of six novel patients with MECP2 duplications due to unbalanced
      rearrangements of the X chromosome.
AB  - Males with duplication of the Xq28 region, including methyl CpG-binding protein 2
      (MECP2), exhibit a characteristic phenotype, including developmental delay,
      intellectual disability, limited or absent speech, limited or absent ambulation,
      and recurrent respiratory infections. We report six males with MECP2 duplications
      identified using array comparative genomic hybridization. The minimal sizes of
      these duplications range from ~0.08 to 14.13 Mb, which, to the best of our
      knowledge, are respectively the smallest and largest minimal size duplications
      molecularly characterized to date. Adjunct metaphase fluorescence in situ
      hybridization analysis further classified these duplications as tandem or as
      products of complex chromosomal rearrangements. Specifically, one complex
      rearrangement was described as a der(12)t(X;12)(q28;q24.33), which is the first
      report of a translocation involving MECP2 on Xq and chromosome 12. The other
      complex rearrangement was described as a rec(X)dup(Xq)inv(X)(p22.32q28)mat.
      Synthesis of the dysmorphic features identified in individuals with rec(X)
      chromosomes, including deletions in the pseudoautosomal region 1 (PAR1) at
      Xp22.33/Yp11.3 and duplications of the distal Xq region including MECP2, revealed
      a high prevalence of undescended testes (7/8) and micropenis (3/8) in this
      cohort. Given that micropenis is rare in the general population, but present in
      38% of individuals in this cohort, a dosage anomaly at one or both loci may be a
      significant risk factor for this condition. Therefore, we recommend microarray
      testing for patients with unexplained micropenis, particularly when accompanied
      by other phenotypic anomalies.

PMID- 22581588
TI  - A challenging case of late-onset gastroschisis.

PMID- 22581589
TI  - The ultrasound-assisted extraction and identification of antifungal substances
      from B. amyloliquefaciens strain NJN-6 suppressing Fusarium oxysporum.
AB  - The primary mechanism underlying antagonism among microorganisms is the
      production of antagonistic substances called antibiotics that inhibit the growth
      of pathogens. In this study, the antagonistic substances produced by the Bacillus
      amyloliquefaciens strain NJN-6 that had antifungal activity against Fusarium
      oxysporum were extracted and identified. The active antifungal substance was
      extracted from dried leavening with ultrasound-assisted extraction (UAE), using n
      -butanol as the extractant. HPLC/ESI-MS was performed to investigate the
      components of the extracts. The results of the study showed that the
      antimicrobial substances consisted of three homologues of the iturin A family
      with molecular weights of 1043, 1057 and 1071 Da and of two homologues of the
      fengycin family with molecular weights of 1477 and 1491 Da. The effects of
      ultrasonic treatment time, extraction time and extractant volume, three major
      methodological parameters, were also studied to determine the optimal conditions
      for extraction. Compared with traditional extraction techniques, UAE is a simple,
      cheap and environmentally friendly method that represents a new option for the
      isolation and identification of lipopeptides and other active compounds. These
      antifungal substances extracted and identified from Bacillus amyloliquefaciens
      NJN-6 will help us to understand its biocontrol mechanism against Fusarium
      oxysporum.

PMID- 22581591
TI  - Optimization of a Saccharomyces cerevisiae fermentation process for production of
      a therapeutic recombinant protein using a multivariate Bayesian approach.
AB  - Various approaches have been applied to optimize biological product fermentation
      processes and define design space. In this article, we present a stepwise
      approach to optimize a Saccharomyces cerevisiae fermentation process through risk
      assessment analysis, statistical design of experiments (DoE), and multivariate
      Bayesian predictive approach. The critical process parameters (CPPs) were first
      identified through a risk assessment. The response surface for each attribute was
      modeled using the results from the DoE study with consideration given to
      interactions between CPPs. A multivariate Bayesian predictive approach was then
      used to identify the region of process operating conditions where all attributes
      met their specifications simultaneously. The model prediction was verified by
      twelve consistency runs where all batches achieved broth titer more than 1.53 g/L
      of broth and quality attributes within the expected ranges. The calculated
      probability was used to define the reliable operating region. To our knowledge,
      this is the first case study to implement the multivariate Bayesian predictive
      approach to the process optimization for the industrial application and its
      corresponding verification at two different production scales. This approach can
      be extended to other fermentation process optimizations and reliable operating
      region quantitation.

PMID- 22581590
TI  - Investigating the impact of chronic atrazine exposure on sexual development in
      zebrafish.
AB  - Atrazine (ATZ) is a selective triazine herbicide used primarily for preemergent
      weed control in corn, sorghum, and sugar cane production. It is one of the most
      widely used herbicides in North America. Some research published over the last
      decade suggests that chronic exposure to environmentally relevant ATZ
      concentrations can adversely impact gonadal development and/or sexual
      differentiation in amphibians and fish, while other studies report no effect, or
      moderate effects. As a result, contrasting conclusions have been published
      regarding the potential effects of the herbicide ATZ on aquatic species. Two near
      identical 4-month studies in 2009 (Study I) and 2010 (Study II) were performed
      investigating the potential for chronic ATZ exposure to affect zebrafish (Danio
      rerio) sexual development and differentiation. Zebrafish were chronically exposed
      to 0, 0.1, 1, 10 MUM ATZ or 1 nM 17beta-estradiol (E2). Fish were histologically
      examined to assign gender and to evaluate potential impacts of E2 or ATZ on
      gonadal development. Exposure to E2 consistently resulted in a significantly
      higher proportion of female fish to normal male fish when compared to unexposed
      fish (both studies). In both studies, ATZ exposure did not significantly
      influence the percentage of female or male fish when compared to unexposed fish.
      A greater percentage of abnormally developed male fish and fish lacking
      differentiated gonadal tissue was observed in Study II E2 exposures but not in
      ATZ exposures. Together, these studies indicate that long-term exposure to ATZ at
      or above environmentally relevant concentrations does not significantly impact
      zebrafish gonadal development or sexual differentiation.

PMID- 22581592
TI  - Rapid detection of large expansions in progressive myoclonus epilepsy type 1,
      myotonic dystrophy type 2 and spinocerebellar ataxia type 8.
AB  - BACKGROUND AND PURPOSE: Human genetic disorders associated with multiple unstable
      repeats resulting in long DNA expansions are difficult to identify by
      conventional polymerase chain reaction (PCR) in routine molecular testing, and
      therefore require time-consuming hybridisation. To improve and expedite the
      diagnostic methods for progressive myoclonus epilepsy (EPM1), myotonic dystrophy
      2 (DM2) and spinocerebellar ataxia 8 (SCA8) caused by dynamic mutations, we
      adapted a repeat primed PCR (RP-PCR) assay which was previously developed for
      testing of other triplet repeat disorders. MATERIAL AND METHODS: The new
      algorithm for molecular analysis was to run a standard PCR to yield alleles in an
      amplifiable range and then run a RP-PCR to detect larger expansions.
      Electrophoresis and visualisation of PCR products on an automatic sequencer were
      applied to determine normal and pathogenic alleles comprising (C4GC4GCG)n in EPM1
      in 44 subjects, (CCTG)n in DM2 in 76 individuals and (CTG)n in SCA8 in 378
      patients. RESULTS: The protocol combining conventional PCR and RP-PCR proved to
      be a rapid and reliable test to diagnose the above named disorders. Among 44
      individuals tested for EPM1, two expanded alleles were identified in 7 patients.
      Out of 76 apparently homozygous subjects, RP-PCR allowed us to detect 56
      expansions specific to DM2, and out of 378 ataxia patients, a large allele of the
      ATXN8OS gene (SCA8) was found in 25 subjects. CONCLUSIONS: Here, for the first
      time, we report detection of large expansions in EPM1 and SCA8 patients. This RP
      PCR assay is high throughput, reproducible and sensitive enough to be
      successfully used for diagnostic purposes.

PMID- 22581594
TI  - Clinical application of the Polish adaptation of the Montreal Cognitive
      Assessment (MoCA) test in screening for cognitive impairment.
AB  - MATERIAL AND METHODS: A group of 115 subjects (36 meeting DSM-IV criteria for
      Alzheimer disease (AD) [Clinical Dementia Rating (CDR) = 1], 42 meeting
      Petersen's criteria for MCI [CDR = 0.5], and 37 cognitively intact controls [CDR
      = 0]) was recruited for the study in the university-based Alzheimer out-patient
      clinic. All participants underwent general medical, neurological, and psychiatric
      examinations. The MoCA, the MMSE, CDR and the short (15-item) version of the
      Geriatric Depression Scale were also applied. RESULTS: Both MCI and AD groups
      exhibited impaired performance on MoCA compared to controls. Polish versions of
      the MMSE and MoCA tests were comparable in discriminating mild dementia from both
      MCI and control groups. The Polish version of the MoCA test performed marginally
      better than MMSE in discriminating MCI from controls. We propose to use the MoCA
      test to screen for MCI using an optimal cut-off score of 24 and to screen for
      dementia using a cut-off score of 19. CONCLUSIONS: The Polish version of the MoCA
      seems effective in the detection of deteriorated cognitive performance and
      appropriate for differentiating impaired from preserved cognitive function in a
      Polish population.

PMID- 22581593
TI  - Factors affecting the quality of life in hemifacial spasm patients.
AB  - BACKGROUND AND PURPOSE: Hemifacial spasm (HFS), a movement disorder manifested by
      unilateral spasms of the muscles innervated by the facial nerve, interferes with
      social life in about 90% of patients, causing social isolation and depression and
      having a significant impact on the quality of life. The aim of the study was to
      assess factors affecting the quality of life in patients with HFS in respect of
      influence of the severity of depression symptoms and botulinum toxin type A (BTX
      A) therapy. MATERIAL AND METHODS: Eighty-five out of 129 patients included in the
      HFS database of the Movement Disorders Outpatient Clinic, Department of
      Neurology, University Hospital, Cracow who fulfilled the inclusion criteria and
      had no exclusion criteria (suffering from concomitant movement disorders, other
      severe chronic diseases or cognitive impairment) were studied. Demographic and
      clinical data (age at onset, disease duration and accompanying symptoms) were
      collected. Severity of HFS was assessed by the five-point clinical scale and
      seven-point Clinical Global Impression scale. Quality of life was assessed with
      the HFS-36 questionnaire and severity of depressive symptoms was evaluated with
      the Beck Depression Inventory. HFS-36 was performed twice, before BTX-A injection
      and two weeks later. RESULTS: The mean global score of HFS-36 was 47 +/- 31
      (maximum: 140 pts). Decreased HFS-36 score resulted from divergent deterioration
      in all subscales included in the questionnaire. Independent risk factors of
      deterioration in HFS-36 were increased severity of HFS and depressive symptoms as
      well as accompanying trismus. The HFS-36 score depended on the number and type of
      accompanying symptoms as well. Botulinum toxin type A therapy led to a
      significant improvement of HFS-36, particularly high in patients with multiple (>
      4) HFS-related symptoms. CONCLUSIONS: The HFS-36 score depends mostly on severity
      of HFS, depressive symptoms and occurrence of accompanying trismus. It improves
      after BTX-A treatment.

PMID- 22581595
TI  - A single-fibre electromyography study of neuromuscular transmission in patients
      with cluster headache.
AB  - BACKGROUND AND PURPOSE: Mutations of CACNA1A, which encodes a neuronal P/Q Ca2+
      channel, are present in patients with familial hemiplegic migraine, and possibly
      in other types of migraine as well. This calcium channel is also involved in
      neuromuscular transmission. In our previous study we confirmed that the single
      fibre electromyography (SFEMG) method can demonstrate a neuromuscular
      transmission deficit in migraine with aura. The aim of our present study was to
      estimate the neurotransmitter dysfunction in cluster headache and to compare the
      results between patients with cluster headache and those with migraine with aura.
      MATERIAL AND METHODS: We selected 6 patients with cluster headache and 6 patients
      with migraine with typical aura. SFEMG of the voluntarily activated extensor
      digitorum communis muscle was performed. RESULTS: The SFEMG results were in the
      normal range in the cluster headache group and in the healthy controls. Slight
      neuromuscular transmission disturbances were present in patients with migraine
      with aura. CONCLUSIONS: The abnormal neuromuscular transmission detectable by
      SFEMG may reflect a genetically determined dysfunction of the P/Q Ca2+ channels
      in a group of migraineurs with aura. Conversely, absence of neuromuscular
      abnormalities in cluster headache patients could be explained by different
      aetiology not resulting in channelopathy. Single-fibre electromyography could be
      a helpful tool in clinically questionable cases in differentiating between
      cluster headache and migraine with aura.

PMID- 22581596
TI  - The usefulness of accelerometric registration with assessment of tremor
      parameters and their symmetry in differential diagnosis of parkinsonian,
      essential and cerebellar tremor.
AB  - BACKGROUND AND PURPOSE: The aim of the study was to perform an analysis of the
      recorded tremor using accelerometry and select those parameters that are the most
      useful in differentiation of tremor types. MATERIAL AND METHODS: We examined 45
      patients with parkinsonian tremor (PT), 39 patients with essential tremor (ET)
      and 35 patients with cerebellar tremor (CT). The control group consisted of 52
      healthy persons. The analysis included tremor intensity, frequency of spectral
      peaks, centre frequency, standard deviation of the centre frequency, and harmonic
      index. Parameters of tremor were compared between particular groups of patients
      with pathological tremor and with the control group. The side-to-side symmetry of
      these parameters was also analysed. RESULTS: Tremor intensity was significantly
      higher in patients than in controls. There was a significant side-to-side
      asymmetry of intensity in all patient groups. Significantly lower peak frequency,
      centre frequency and standard deviation of centre frequency were found in
      patients compared to the control group. The frequency was symmetric in ET and in
      controls, but asymmetric in other subjects. The differences between hands
      regarding the standard deviation of centre frequency were significantly greater
      in all patient groups than in controls, who revealed no difference of this
      parameter between sides. Harmonic index was significantly greater and asymmetric
      in all groups of patients when compared to the control group. CONCLUSIONS:
      Standard deviation of centre frequency and harmonic index are the most valuable
      variables in differentiation of tremor. The assessment of symmetry of tremor
      parameters is useful in discrimination of various types of pathological tremor.

PMID- 22581597
TI  - Intraoperative magnetic resonance-guided frameless stereotactic biopsies -
      initial clinical experience.
AB  - BACKGROUND AND PURPOSE: We present our early experience in intraoperative
      magnetic resonance (iMRI)-guided stereotactic frameless biopsies with special
      regard to its safety, efficacy and diagnostic value. MATERIAL AND METHODS: The
      records of patients who underwent frameless stereotactic iMRI-guided biopsies
      between June 2009 and April 2011 were analysed prospectively. All the operations
      were performed under local anaesthesia, with the use of a passive side-cutting
      biopsy needle. The needle was introduced into the pathological lesion with the
      help of optic neuronavigation system guidance. The iMRI scans served as reference
      images. We analysed the patients' demographic and epidemiological data, the
      preparation and surgery times, diagnostic values of collected specimens, lengths
      of the hospital stay (LOS) and the complication rate. RESULTS: Fifteen iMRI
      guided stereotactic biopsies were performed in the analysed period. The mean
      patient age was 52 +/- 18 yrs, the median WHO score was 2 (range: 1-3), there
      were 9 (60%) males in the study group. The average preparation time was 53 +/- 24
      minutes and the operation time 69 +/- 25 minutes. No major complications were
      noted. The median total length of hospital stay was 5 days. The histopathological
      diagnoses were as follows: glioblastoma multiforme - 6 cases, low-grade gliomas -
      4 cases, lymphomas - 3 cases, and other pathologies - 2 cases. In all the cases
      biopsy material allowed specified histopathological diagnoses to be obtained.
      CONCLUSIONS: Frameless stereotactic iMRI-guided brain tumour biopsy is a safe and
      diagnostically effective procedure. The use of iMRI might increase the diagnostic
      value and safety of stereotactic biopsy and positively influence its economic
      balance.

PMID- 22581598
TI  - [Cryptogenic stroke - patent foramen ovale - migraine with aura: incidental triad
      or significant relationship? Part I].
AB  - In the first part of the paper we discuss the association between patent foramen
      ovale (PFO) and cryptogenic stroke. Patent foramen ovale is a remnant of the
      fetal circulation, found in about quarter of the general population. According to
      many authors, this common anatomical anomaly is of no or limited clinical
      significance. However, the results of some clinical studies suggest higher
      prevalence of PFO among subjects with either cryptogenic stroke or migraine with
      aura. To date, the answer to the question whether PFO is an independent risk
      factor for stroke remains equivocal. The purpose of this review is to discuss the
      role of PFO in pathophysiology of both symptomatic and asymptomatic ischaemic
      lesions and to analyze the coexisting factors that increase the risk of stroke.
      We also discuss the effectiveness of either pharmacological treatment or PFO
      closure in secondary stroke prevention.

PMID- 22581599
TI  - [Cryptogenic stroke - patent foramen ovale - migraine with aura: incidental triad
      or significant relationship? Part II].
AB  - In the second part of the paper, we discuss the relationship between migraine
      with aura and either patent foramen ovale (PFO) or stroke. The results of the
      studies suggest that PFO with right-to-left shunt is more prevalent among
      patients suffering from migraine with aura. Moreover, migraine with aura is a
      risk factor for ischaemic stroke in women and the risk increases when they have
      additional vascular risk factors such as taking oral contraception and smoking.
      However, the pathophysiology of these phenomena remains hypothetical. The most
      frequently reported theory suggests paradoxical embolism as a mechanism of the
      above-mentioned pathologies. In this paper we compare the pros and cons of the
      general theories. We discuss the percutaneous closure of PFO in patients with
      migraine, regarding the benefit/risk ratio.

PMID- 22581600
TI  - [Pathogenetic justification of statin use in ischaemic stroke prevention
      according to inflammatory theory in development of atherosclerosis].
AB  - There is an inflammatory component in the pathogenesis of ischaemic stroke, which
      plays an important role in inducing atherothrombotic and embolic stroke. Statins,
      HMG-CoA (3-hydroxy-3-methyl-glutaryl-coenzyme A) reductase inhibitors are widely
      used in the primary and secondary prevention of ischaemic stroke. It has been
      proved that beyond their main effect on inhibition of endogenous cholesterol,
      they also modify the inflammatory process. Additional benefits from the use of
      statins result from their effect on the immune system.  Increased risk of
      recurrent vascular episodes and risk of death after statin withdrawal in patients
      with vascular disorders is connected with termination of the anti-inflammatory
      effect of these drugs. The authors highlight that because of the anti
      inflammatory effect of statins it is reasonable to use them in all patients at
      risk of ischaemic stroke, including those with atrial fibrillation.

PMID- 22581601
TI  - Perfusion sensitive contrast-enhanced magnetic resonance imaging of
      dysembryoplastic neuroepithelial tumour: a new neuroimaging finding.
AB  - Dysembryoplastic neuroepithelial tumours (DNTs) are benign lesions affecting
      young people and are associated with epilepsy. There have been described more
      than 300 cases in the literature and the clinical, pathological and radiological
      findings are well known. Recent advances in neuroimaging allow the acquisition of
      cerebral microcirculation parameters by perfusion weighted imaging, giving
      additional diagnostic information improving the diagnostic accuracy. The aim of
      this study is to show the perfusion sensitive contrast-enhanced magnetic
      resonance imaging findings of a case of DNT as an additional neuroradiological
      finding. Further investigation of microcirculation parameters may be helpful to
      establish the correct diagnosis of such tumours.

PMID- 22581602
TI  - Development of Guillain-Barre syndrome in a patient with multiple sclerosis
      during treatment with glatiramer acetate.
AB  - Some observations suggest that in some patients with multiple sclerosis
      demyelination may affect the central and peripheral nervous systems at the same
      time. The influence of immunomodulatory therapy on peripheral nervous system
      damage in these patients is still unknown. We present a 43-year-old male patient
      with multiple sclerosis diagnosed at the age of 35 in whom flaccid tetraparesis
      with dysaesthesia preceded by paraesthesias of four limbs occurred one year after
      starting glatiramer acetate. The course of peripheral nervous system disease and
      results of cerebrospinal fluid examination and electromyography confirmed
      Guillain-Barre syndrome. Interfering in the immunological system, glatiramer
      acetate may have contributed to the development of the symptoms of Guillain-Barre
      syndrome in our patient. The final improvement of the patient's condition may
      have resulted not only from the applied treatment and the natural course of the
      disease, but may have also been associated with the discontinuation of glatiramer
      acetate.

PMID- 22581603
TI  - Intraventricular dysembryoplastic neuroepithelial tumour: case report.
AB  - Dysembryoplastic neuroepithelial tumour (DNT) is located in the cerebral cortex
      with very few exceptions. In this article, an extremely rare case of
      intraventricular DNT originating from the septum pellucidum is reported.  A 25
      year-old woman presented with 5-month history of headache. Cranial magnetic
      resonance imaging (MRI) scans revealed a mass in the right lateral and third
      ventricle which was hypointense on T1-weighted image, and hyperintense on T2
      weighted images. No contrast enhancement was detected. The lesion was excised
      totally using a transcallosal-transventricular approach. Immunohistochemical
      examination revealed DNT. The patient was discharged without any neurological
      deficits.  Intraventricular DNT presents with symptoms of increased intracranial
      pressure rather than seizures. Distinguishing DNT from other intraventricular
      tumours is essential as DNT is characterized by benign clinical course and does
      not require adjuvant therapy.

PMID- 22581604
TI  - Large cerebellopontine angle tuberculoma: a case report.
AB  - Tuberculoma involving the cerebellopontine angle is very rare. Preoperative
      neuroradiological features of such lesions may mimic neoplastic lesions and
      postoperative histopathological study brings the ultimate diagnosis. Here we
      present a patient with a large tuberculoma at the cerebellopontine angle who had
      another small lesion at the right fronto-basal region and was managed by surgical
      excision of the cerebellopontine angle lesion along with post-surgical
      antitubercular therapy for 18 months. On the 14th postoperative day, the patient
      developed status epilepticus, left hemiplegia and left-sided complete hearing
      loss. Computed tomography showed right frontal oedema. Then he recovered his
      motor function slowly and incompletely but left-sided hearing loss remained
      unchanged. Magnetic resonance imaging of the brain at 18 months after surgery
      showed no residual lesion with right frontal cortical atrophy.

PMID- 22581605
TI  - Onion grating as an alternative to pilocarpine drops in a patient with Adie
      pupil.

PMID- 22581607
TI  - Retracted: Prediction of posttranslational modification sites from sequences with
      kernel methods.

PMID- 22581606
TI  - Simulation of patella alta and the implications for in vitro patellar tracking in
      the ovine stifle joint.
AB  - Patella alta is associated with adverse cartilage adaptations, patellofemoral
      pain, and instability. It is defined by a relatively long patellar tendon and
      patella positioned in a more proximal location within the patellar groove of the
      femur. This study used the ovine stifle joint model to investigate the effect of
      patellar tendon lengthening on the 3D passive kinematics of the patellofemoral
      and tibiofemoral joints. Eight patellar tendons were lengthened in 2 mm
      increments up to a maximum of 12 mm (20%) using a device placed in series with
      the transected patellar tendon. Three-dimensional kinematics were measured in the
      intact joint and at each increment of patellar tendon length (L(T)) during
      passively induced tibiofemoral flexion. Patellar flexion angle was linearly
      correlated with tibial flexion angle in the intact joint, and this correlation
      persisted after tendon lengthening (R = 0.897-0.965, p < 0.01). Patellofemoral
      kinematics expressed as a function of tibial flexion angle were significantly
      altered by L(T) increases >9%. In contrast, when patellofemoral kinematics were
      expressed as a function of patellar flexion angle they were not significantly
      altered by increases in L(T). Tibiofemoral kinematics were not affected by the
      L(T) increases. These results demonstrate that for a given tibial flexion angle,
      patellar tendon lengthening alters the patellar flexion angle. However, for a
      given patellar flexion angle, the orientation of the patella in the remaining
      five degrees of freedom is unchanged, implying a repeatable path of patellar
      motion.

PMID- 22581609
TI  - Bacteria from Ips sexdentatus (Coleoptera: Curculionidae) and their biocontrol
      potential.
AB  - Ips sexdentatus (Coleoptera: Curculionidae) is one of the most destructive pests
      of the spruce trees in Europe. In this study, we have isolated and characterized
      culturable bacteria from I. sexdentatus and tested their insecticidal activity
      against the last instar larvae of the pest as a possible biocontrol agent. A
      total of eight bacterial isolates was determined and four of them were identified
      at species level, and the others were identified at genus level. Isolates were
      identified as Stenotrophomonas maltophilia (Is1), Rahnella sp. (Is2), Pseudomonas
      sp. (Is3), Bacillus sp. (Is4), Alcaligenes faecalis (Is5), Panteoea agglomerans
      (Is6), Pseudomonas fluorescens (Is7) and Serratia sp. (Is8) based on their
      morphological, biochemical and molecular characteristics. Insecticidal effects of
      bacterial isolates were performed on the last instar larvae of the pest. The
      highest insecticidal activity was obtained from P. fluorescens (Is7) with 73%
      mortality within 10 days after inoculation (p < 0.05). Mortality values of the
      other isolates ranged from 20 to 53%. This study suggests that Pseudomonas
      fluorescens (Is7) seems to be a good candidate as a possible biocontrol agent
      against I. sexdentatus, and provides suitable strains that can be modified to
      express insecticidal toxins and/or other detrimental substances to develop new
      control methods for I. sexdentatus.

PMID- 22581610
TI  - Long-term survival with diaphanospondylodysostosis (DSD): survival to 5 years and
      further phenotypic characteristics.
AB  - We report on the natural history of diaphanospondylodysostosis (DSD) in the
      longest known survivor. DSD is a rare form of autosomal recessive vertebral
      dysotosis recently identified to be caused by a mutation in the BMPER gene. This
      condition is characterized by absent or severely delayed ossification of
      vertebral bodies, short broad thorax, short neck, protuberant abdomen, marked
      respiratory insufficiency, and normal appendicular skeleton. It is one of a
      number of spinal dysostoses, which are a heterogeneous group of axial skeletal
      malformations occurring during blastogenesis with continued evolution after
      birth. Significant medical intervention and at-home support contributed to the
      long-term survival of our patient. The patient had tracheomalacia, which resulted
      in respiratory insufficiency with thoracic insufficiency syndrome (TIS).
      Tracheostomy and vertical expandable prosthetic titanium rib (VEPTR) insertion
      operations ameliorated his symptoms. In addition, comprehensive physical and
      occupational therapy was performed due to chronic hypotonia. A consistent feature
      of all described DSD cases thus far are renal findings of dysplasia, nephrogenic
      rests or nephroblastomatosis, and/or cysts. The patient's renal cysts were
      monitored with serial ultrasounds at approximately 6-month intervals. The patient
      was diagnosed with bilateral renal cysts by ultrasound as a neonate, with
      eventual diagnosis at approximately 20 months of age with nephroblastoma
      suggesting this maybe an intrinsic part of DSD. The lack of other cases with
      nephroblastoma is likely related to the previously reported short period of
      survival.

PMID- 22581612
TI  - Biodegradation behavior of silk fibroin membranes in repairing tympanic membrane
      perforations.
AB  - Silk fibroin (SF) from silkworms has been widely studied as a biomaterial. The
      degradation behavior of silk biomaterials is important for medical applications,
      but few studies have examined long-term degradation behavior in vivo. In this
      study, we investigated the degradation behavior of SF membranes in vitro and in
      vivo. For the in vitro assay, we observed degradation of silk membranes in
      phosphate buffered saline, culture media, and an enzyme (proteinase K) solution.
      In the proteinase K solution, 80% of the silk membranes degraded within 10 days.
      Silk membranes exhibited no cytotoxicity toward L929 cells and rat tissues. To
      investigate the degradation of silk membranes in vivo, they were implanted
      subcutaneously in rats and harvested 19 months after surgery. Scanning electron
      microscopy imaging and histological analysis of silk membrane explants showed
      that they broke into several pieces after 16 months. Results show that silk
      membranes are biocompatible and display excellent long-term degradation behavior
      when used as biomaterials.

PMID- 22581611
TI  - Maternal hemodynamics at 11-13 weeks of gestation and preterm birth.
AB  - OBJECTIVE: Women who experience preterm birth (PTB) are at increased risk of
      cardiovascular morbidity and mortality in the subsequent decades. Individuals
      with cardiovascular disorders have increased central aortic systolic blood
      pressure (SBP(Ao)) and arterial stiffness, assessed by pulse wave velocity (PWV)
      and augmentation index (AIx). The aim of this screening study was to evaluate
      SBP(Ao), PWV and AIx at 11-13 weeks' gestation in women who delivered preterm.
      METHODS: This was a prospective study in singleton pregnancies at 11 + 0 to 13 +
      6 weeks' gestation. Maternal history and characteristics were recorded, and PWV,
      AIx and SBP(Ao) were measured. We compared these parameters in women who had
      spontaneous (n = 244) or iatrogenic (n = 110) PTB before 37 weeks' gestation and
      before 34 weeks with those in women who had term delivery (n = 7489). RESULTS:
      Compared with women who had term delivery, women who had iatrogenic PTB had
      significantly higher AIx (1.08 (interquartile range (IQR), 0.91-1.27) multiples
      of the median (MoM), vs. 1.00 (IQR, 0.86-1.16) MoM) and SBP(Ao) (1.06 (IQR, 0.98
      1.15) MoM vs. 1.00 (IQR, 0.93-1.07) MoM). However, there was no significant
      difference in AIx, PWV or SBP(Ao) between those who had spontaneous PTB and those
      who had term delivery. These findings were similar for those who had PTB at < 34
      and < 37 weeks' gestation. CONCLUSION: Women who had iatrogenic PTB, but not
      those who had spontaneous PTB, have increased SBP(Ao) and arterial stiffness that
      is apparent from as early as the first trimester of pregnancy.

PMID- 22581613
TI  - [Tattoos - harmless decoration or health hazard?].

PMID- 22581614
TI  - Structural and catalytic role of two conserved tyrosines in Delta-class
      glutathione S-transferase from Locusta migratoria.
AB  - Glutathione S-transferases (GSTs) are an important family of detoxifying enzymes
      and play a key role in pesticide resistance in the insect. Tyrosine is essential
      for its detoxification function. In the present study, two conserved tyrosine
      residues are located at positions 108 and 116 in H-site of LmGSTD1. To elucidate
      how the two residues participate in the catalytic process and keeping structural
      stability, four mutants, Y108A, Y108E, Y116A, and Y116E, were generated. It was
      found that the four mutants affected the specific activity of LmGSTD1 in various
      degrees, depending on the types of substrate and reaction mechanism. Steady-state
      kinetics assay revealed that Y108E and Y116E had a significant influence on GSH
      binding ability, which indicates the two tyrosine residues of H-site contribute
      to topology rearrangement of G-site. Both Y116A and Y116E exhibited lower CDNB
      binding affinity, suggesting that Y116 takes part in hydrophobic substrate
      binding. The thermostability assay, intrinsic, and 8-anilino-1
      naphthalenesulfonic acid (ANS) florescence results showed that the two tyrosine
      residues were involved in regulation of active-site conformation. Finally,
      homology modeling provided evidence that the two tyrosines in H-site participate
      in hydrophobic substrate binding. Furthermore, Y108 is closer to the S atom of S
      hexylglutathione. In conclusion, the two tyrosines in LmGSTD1 are important
      residues in both the catalytic process and protein stability.

PMID- 22581615
TI  - Effect of initial bacteria concentration on hydrogen gas production from cheese
      whey powder solution by thermophilic dark fermentation.
AB  - Dark fermentative hydrogen gas production from cheese whey powder solution was
      realized at 55 degrees C. Experiments were performed at different initial biomass
      concentrations varying between 0.48 and 2.86 g L(-1) with a constant initial
      substrate concentration of 26 +/- 2 g total sugar (TS) per liter. The highest
      cumulative hydrogen evolution (633 mL, 30 degrees C), hydrogen yield (1.56 mol
      H(2) mol(-1) glucose), and H(2) formation rate (3.45 mL h(-1) ) were obtained
      with 1.92 g L(-1) biomass concentration. The specific H(2) production rate
      decreased with increasing biomasss concentration from the highest value (47.7 mL
      g(-1) h(-1) ) at 0.48 g L(-1) biomass concentration. Total volatile fatty acid
      concentration varied beetween 10 and 14 g L(-1) with the highest level of 14.2 g
      L(-1) at biomass concentration of 0.48 g L(-1) and initial TS content of 28.4 g
      L(-1) . The experimental data were correlated with the Gompertz equation and the
      constants were determined. The most suitable initial biomass to substrate ratio
      yielding the highest H(2) yield and formation rate was 0.082 g biomass per gram
      of TS.

PMID- 22581616
TI  - Application of epigenome-modifying small molecules in induced pluripotent stem
      cells.
AB  - Recent breakthroughs in generating induced pluripotent stem cells (iPSCs) using
      four defined factors have revealed the potential utility of stem cells in
      biological research and clinical applications. However, the low efficiency and
      slow kinetics of reprogramming related to producing these cells and underlying
      safety issues, such as viral integration and genetic and epigenetic abnormalities
      of iPSCs, hamper the further application of iPSCs in laboratory and clinical
      settings. Previous studies have suggested that reprogramming efficiency can be
      enhanced and that reprogramming kinetics can be accelerated by manipulating
      epigenetic status. Herein, we review recent studies on the application of
      epigenome-modifying small molecules in enhancing reprogramming and functionally
      replacing some reprogramming factors. We mainly focus on studies that have used
      small molecules to interfere with epigenome-modifying enzymes, such as DNA
      methyltransferase, histone acetyltransferase, and histone methyltransferase. The
      potential use of these small molecules in inducing iPSCs and new ways to identify
      small molecules of higher potency and fewer side effects are also discussed.

PMID- 22581617
TI  - Synthesis of dual-mesoporous silica using non-ionic diblock copolymer and
      cationic surfactant as co-templates.

PMID- 22581618
TI  - Are old males still good males and can females tell the difference? Do hidden
      advantages of mating with old males off-set costs related to fertility, or are we
      missing something else?
AB  - Sperm function generally declines with male age. Paradoxically, females of many
      species still choose to mate with old males rather than young males. Females
      choosing old mates may suffer reduced fertilization rates and an increased
      incidence of birth defects in offspring, lowering fitness which may in turn lead
      to conflict between the sexes. This apparent paradox has generated much interest
      from theorists, but whether this paradox presents in nature remains equivocal.
      Empirical studies have found mixed support for both a decline in fertility with
      male age and age-based female mate preference. Here, we examine recent evidence
      for this paradox, identify confounding variables, highlight areas that deserve
      further investigation, and suggest avenues for future research.

PMID- 22581619
TI  - Variability in expression of a familial 2.79 Mb microdeletion in chromosome
      14q22.1-22.2.
AB  - Deletions in chromosome 14q22-23 have been associated with variable
      manifestations including malformations of the eye, limbs, palate, and brain, and
      with developmental and growth delay. Haploinsufficiency of BMP4, OTX2 and
      possibly SIX6 are thought to contribute to the phenotype. We present a three
      generation family with four individuals carrying a 2.79 Mb microdeletion 14q22.1
      22.2 encompassing BMP4 but not OTX2 nor SIX6. The highly variable manifestations
      in this family range from multiple congenital malformations with Robin sequence,
      microphthalmia, postaxial polydactyly, and developmental delay in the index
      patient to cleft uvula, growth delay, and mild developmental delay in her sister.
      The adults have a normal intelligence, postaxial polydactyly, and short stature
      or early cataract. Genotype-phenotype correlations suggest that the severity of
      eye manifestations in 14q22 deletions are influenced by the size of the deletion,
      but the marked intrafamilial variability observed in this family, as well as in
      familial BMP4 or OTX2 intragenic mutations points to additional modifiers outside
      this region.

PMID- 22581620
TI  - An investigation into the effect of amphiphilic siloxane oligomers on dermal
      fibroblasts.
AB  - This study investigates the effect of well-defined poly(dimethylsiloxane)
      poly(ethylene glycol) (PDMS-PEG) ABA linear block co-oligomers on the
      proliferation of human dermal fibroblasts. The co-oligomers assessed ranged in
      molecular weight (MW) from 1335 to 5208 Da and hydrophilic-lipophilic balance
      (HLB) from 5.9 to 16.6 by varying the number of both PDMS and PEG units. In
      general, it was found that co-oligomers of low MW or intermediate hydrophilicity
      significantly reduced fibroblast proliferation. A linear relationship between
      down-regulation of fibroblast proliferation, and the ratio HLB/MW was observed at
      concentrations of 0.1 and 1.0 wt % of the oligomers. This enabled the structures
      with highest efficiency to be determined. These results suggest the possible use
      of the PEG-PDMS-PEG block co-oligomers as an alternative to silicone gels for
      hypertrophic scar remediation.

PMID- 22581621
TI  - Does three-dimensional power Doppler ultrasound predict histopathological
      findings of uterine fibroids? A preliminary study.
AB  - OBJECTIVES: To compare three-dimensional (3D) power Doppler sonographic
      characteristics of fibroids with histopathological parameters. METHODS: We
      evaluated sonographically 73 fibroids before myomectomy or hysterectomy. For
      each, the total fibroid volume, a shell of 3 mm and a 1-cm(3) spherical sample
      from the most vascularized area on subjective assessment were captured. 3D power
      Doppler vascularization index (VI), flow index (FI) and vascularization flow
      index (VFI) were generated in the acquired volumes. The degree of cellularity,
      ischemic necrosis and fibrosclerosis, as well as CD31 and Ki-67 staining for
      vascular density and proliferation index, respectively, were estimated using the
      surgical sample. Pathological data were considered as dependent variables and
      ultrasound data as independent variables in multivariable logistic regression
      models including patients' characteristics. RESULTS: A high histological
      'cellular activity score', combining hypercellularity, a fibrosclerosis rate <
      25% and positive Ki-67 staining, was statistically related in multivariate
      analyses to high 3D power Doppler VI in spherical samples (odds ratio (OR), 1.1
      (95% CI, 1.0-1.3), P < 0.05) and VFI (OR, 1.3 (95% CI, 1.0-1.8), P < 0.05).
      Positive CD31 staining was statistically related to high 3D power Doppler VI in
      spherical samples (OR, 1.1 (95% CI, 1.0-1.3), P < 0.05). In contrast, ischemic
      necrosis was statistically related to low 3D power Doppler VI in the total volume
      (OR, 0.6 (95% CI, 0.4-1.0), P < 0.05) and VFI (OR, 0.4 (95% CI, 0.1-1.1), P <
      0.05). CONCLUSION: Vascular density, ischemic necrosis and histological cellular
      activity score are statistically significantly associated with some 3D power
      Doppler indices.

PMID- 22581622
TI  - Genome-wide association mapping with longitudinal data.
AB  - Many genome-wide association studies have been performed on population cohorts
      that contain phenotype measurements at multiple time points. However, standard
      association methodologies only consider one time point. In this paper, we propose
      a mixed-model-based approach for performing association mapping which utilizes
      multiple phenotype measurements for each individual. We introduce an analytical
      approach to calculate statistical power and show that this model leads to
      increased power when compared to traditional approaches. Moreover, we show that
      by using this model we are able to differentiate the genetic, environmental, and
      residual error contributions to the phenotype. Using predictions of these
      components, we show how the proportion of the phenotype due to environment and
      genetics can be predicted and show that the ranking of individuals based on these
      predictions is very accurate. The software implementing this method may be found
      at http://genetics.cs.ucla.edu/longGWAS/.

PMID- 22581623
TI  - Multiple morphologies of ventricular tachycardia assessed by implantable
      cardioverter-defibrillator electrograms in a patient with Chagas disease,
      successfully treated with catheter ablation: modern problems, old solutions.

PMID- 22581624
TI  - Radiotherapy and pacemaker: 80 Gy to target close to the device may be feasible.

PMID- 22581625
TI  - A cross-sectional study of quality of life in an elderly population (75 years and
      over) with atrial fibrillation: secondary analysis of data from the Birmingham
      Atrial Fibrillation Treatment of the Aged study.
AB  - AIMS: To compare the quality of life (QoL) of those in atrial fibrillation (AF)
      aged 75 years and over with that of the general population, to explore what
      factors affect the QoL of those with AF, and to assess the sensitivity of the
      EuroQol (EQ-5D) and Short-Form 12 (SF-12) generic health questionnaires in
      detecting differences in health status in those with AF in this age group.
      METHODS AND RESULTS: The study population was 1762 men and women aged 75 years
      and over with confirmed AF who attended a randomization clinic for the Birmingham
      Atrial Fibrillation Treatment of the Aged (BAFTA) study, a primary care based
      trial of stroke prevention. Patients self-completed the EQ-5D and SF-12
      questionnaires, and a simple measure of disability (Rankin). Cardiovascular co
      morbidities were collected and number of drugs used as an additional proxy for co
      morbidity. Quality-of-life outcomes were compared with general population samples
      of the same age. On multiple regression, female gender, greater medication use,
      and disability were independently associated with lower QoL scores in AF. Those
      in AF with a Rankin score >=2 had lower QoL scores, while those with a Rankin
      score <2 had higher scores than the general population. Increasing co-morbidity
      was associated with reduced QoL scores, with the EQ-5D and SF-12 Physical
      Component Score showing similar sensitivity to these associations, and the SF-12
      Mental Component Score showing less sensitivity. CONCLUSION: In the absence of co
      morbidity, chronic AF has little impact on generic QoL in an elderly non-acutely
      ill population.

PMID- 22581626
TI  - [Data quality or differences in oncological care? - standards of reporting for
      cancer survival analyses based on registry data].
AB  - BACKGROUND: The results of population-based cancer survival analyses are
      essential criteria with regard to the evaluation of oncological care. Their use
      and their interpretation as such require knowledge and transparency with regard
      to the data basis in order to avoid inadequate conclusions. METHOD: The working
      group 'survival analysis' of the Association of Population-Based Cancer
      Registries in Germany (GEKID) has identified factors within cancer registration
      and data evaluation which may distort population-based cancer survival analyses
      to a relevant degree. Recommendations in terms of standards of reporting were
      developed by mutual consent following empirical studies and discussions within
      GEKID. RESULTS: We provide a list of 17 indicators to be taken into account and
      to be presented within the scope of population-based survival analyses.
      CONCLUSIONS: Referring to the "standards of reporting concerning population-based
      cancer survival analyses" introduced by GEKID there is a proposal on data
      transparency on hand, which might contribute substantially to the assessability
      of outcome quality in oncological care.

PMID- 22581627
TI  - Tenofovir: quo vadis anno 2012 (where is it going in the year 2012)?
AB  - Twenty years after its original discovery, tenofovir has acquired a crucial
      position in the fight against human immunodeficiency virus (HIV). First,
      tenofovir disoproxil fumarate (TDF) is not only efficacious against, and has been
      licensed for the treatment of HIV (AIDS), but also HBV (hepatitis B). Second, for
      the treatment of HIV infections, TDF can be used in combination with other anti
      HIV drugs, such as emtricitabine (combination termed Truvada((r))) and Truvada
      can be further combined with efavirenz, rilpivirine, elvitegravir, atazanavir, or
      darunavir, as a single once-daily oral pill. Third, Truvada can be used
      prophylactically to prevent transmission of HIV infection. And fourth, to prevent
      sexual HIV transmission, tenofovir could also be used topically (i.e., as a
      vaginal gel).

PMID- 22581628
TI  - Isolation of the magic-size CdSe nanoclusters [(CdSe)13(n-octylamine)13] and
      [(CdSe)13(oleylamine)13].

PMID- 22581630
TI  - How Kizer healed the VA.

PMID- 22581629
TI  - Phage-derived fully human antibody scFv fragment directed against human vascular
      endothelial growth factor receptor 2 blocked its interaction with VEGF.
AB  - Vascular endothelial growth factor receptor 2 (VEGFR-2) plays a critical role in
      tumor angiogenesis. None therapeutic antibodies targeting VEGFR-2 are available
      in clinical use. Herein, we describe the screening of a new single-chain antibody
      fragment (scFv) targeting extracellular domain 3 of human VEGFR-2 (kinase insert
      domain-containing receptor [KDR]3) from Griffin phage display scFv library. A
      comprehensive sequence analysis was performed to assign the framework and
      complementary-determining regions. The scFv exerted particular binding sites to
      KDR3 on molecular docking, and the binding affinity was further convinced by
      binding analysis both in quantitative ELISA and real-time kinetic determination
      by biosensors (K(D) = 40 nM). Finally, the scFv was revealed to inhibit VEGF
      stimulated proliferation of human umbilical vein endothelial cells (HUVECs;
      IC(50) = 5 nM) and to inhibit HUVEC migration significantly at 17 nM. Taken
      together, our results indicate that we have successfully isolated a scFv which
      differentially recognizes KDR3 and has potential clinical applications in the
      treatment of angiogenesis related diseases.

PMID- 22581631
TI  - US efforts to limit marketing of unhealthy food to children are delayed.

PMID- 22581632
TI  - Another doctor should investigate all hospital deaths.

PMID- 22581633
TI  - More psychiatrists attack plans for DSM-5.

PMID- 22581634
TI  - Endoscopic dacryocystorhinostomy with double posteriorly based nasal and lacrimal
      flaps: a prospective randomized controlled trial.
AB  - OBJECTIVES: To conduct the first prospective randomized controlled trial
      assessing and comparing the safety and efficacy of endoscopic
      dacryocystorhinostomy (DCR) with double posteriorly based nasal and lacrimal
      flaps to conventional endoscopic DCR in adult patients with acquired complete
      nasolacrimal obstruction. STUDY DESIGN: A prospective randomized controlled
      study. SETTING: General hospital. SUBJECTS AND METHODS: Seventy-four adult
      patients with a total of 80 procedures were recruited to undergo endoscopic DCR.
      They were prospectively equally randomized into 2 groups: endoscopic DCR with
      flaps (group I) and conventional endoscopic DCR (group II). Regular follow-up
      settings were done to document the patient's subjective improvement, judge ostium
      patency on irrigation, and record any complications. RESULTS: Endoscopic DCR with
      flaps had a higher (92.1%) but nonsignificant difference in success rate when
      compared with conventional endoscopic DCR (87.4%). There was no significant
      difference between the 2 techniques in operative time, adverse events, and
      tolerability of the technique to be done under local anesthesia with minimal
      sedation. Group I demonstrated a significantly lower number of debridement
      sessions than did group II. CONCLUSION: Endoscopic DCR with double posteriorly
      based nasal and lacrimal flaps provides a viable alternative to conventional
      endoscopic DCR in managing acquired nasolacrimal duct obstructions in adults. It
      has a comparable success rate, operative time, and safety profile, with a
      suggestion of a better healing profile in terms of mucosal recovery, wound
      healing, and less need for debridement sessions.

PMID- 22581635
TI  - Recurrent laryngeal nerve monitoring during thyroid surgery: normative vagal and
      recurrent laryngeal nerve electrophysiological data.
AB  - OBJECTIVE: Injury to the recurrent laryngeal nerve (RLN) remains a significant
      cause of morbidity during thyroid surgery. Intraoperative nerve monitoring (IONM)
      is being applied in many centers to facilitate nerve identification. The aim of
      this study was to elucidate normative human vagal and recurrent laryngeal nerve
      electromyograhic (EMG) parameters during standard IONM application. STUDY DESIGN:
      A prospective IONM study conducted over an 8-month period. Internal review board
      (IRB) approval was obtained. SETTINGS: Department of Otolaryngology, Division of
      Thyroid and Parathyroid Surgery, Massachusetts Eye and Ear Infirmary, Boston.
      SUBJECTS AND METHODS: All patients who were scheduled for routine thyroid,
      parathyroid, or neck exploration surgery were invited to participate. All
      patients had a preoperative and postoperative laryngeal examination to assess
      vocal cord function. Any patient with an abnormal preoperative laryngeal
      examination was excluded. RESULTS: Fifty-eight patients participated in this
      study. The right and left RLN latencies were similar. The left vagus latency was
      greater than the right vagus but was not significant. The RLN latency was
      significantly less than the vagus nerve. The right vagus nerve amplitude was
      significantly greater than the left. There was no difference between male and
      female amplitudes for either the RLN or vagus nerve. CONCLUSION: This study
      highlights the electrophysiological/EMG differences and similarities between the
      RLN and vagus nerve. Normative amplitude measurements for bilateral RLN and vagus
      nerve stimulation are presented. There are limited data available in the
      literature on normal RLN and vagal EMG signals generated during thyroid surgery.

PMID- 22581636
TI  - Sleep apnea in children with laryngomalacia: diagnosis via sedated endoscopy and
      objective outcomes after supraglottoplasty.
AB  - OBJECTIVE: The authors study the contribution of laryngomalacia to obstructive
      sleep apnea syndrome (OSAS) in children older than 12 months. The clinical and
      polysomnographic outcomes in patients with OSAS who underwent a supraglottoplasty
      were also studied. SETTING: Tertiary care children's hospital. STUDY DESIGN: A
      case series with chart review. SUBJECTS AND METHODS: A review of consecutive
      pediatric patients diagnosed with both OSAS and state-dependant laryngomalacia
      (SDL) between 2005 and 2008. The diagnosis of SDL was made via laryngoscopy under
      light general anesthesia (sleep endoscopy). All subjects underwent a
      supraglottoplasty. RESULTS: A total of 43 patients met inclusion criteria, and 36
      patients had complete pre- and postoperative data available for review. The apnea
      hypopnea index (AHI) score decreased following supraglottoplasty for 33 (92%; 95%
      confidence interval [CI], 78%-98%) of the 36 patients. The mean (SD) change in
      AHI score (calculated as the postoperative minus the preoperative measure) was 
      9.2 (11.2), representing a statistically significant reduction (95% CI, -13.0 to 
      5.5; P < .0001). The mean (SD) preoperative AHI was 13.3 (12.9). The minimum
      oxygen saturation increased following supraglottoplasty for 21 (58%; 95% CI, 41%
      74%). The mean (SD) change in the minimum oxygen saturation was 3.5 (8.3), which
      was a statistically significant increase (95% CI, 0.7-6.3; P = .015). CONCLUSION:
      Laryngomalacia may contribute significantly to OSAS in some children who are 12
      months and older. Sleep endoscopy appears to be an effective method in the
      diagnosis of SDL. When present, a supraglottoplasty can be an effective procedure
      and may significantly improve symptoms of OSAS.

PMID- 22581637
TI  - Distant metastases and survival prediction in head and neck squamous cell
      carcinoma.
AB  - OBJECTIVE: This study was designed to identify the risk factors associated with
      distant metastases (DM) and survival outcomes in patients with head and neck
      squamous cell carcinoma (HNSCC). STUDY DESIGN: Database analysis plus chart
      review. SETTING: Tertiary care academic medical center. SUBJECTS AND METHODS:
      Four hundred four eligible patients were involved who were treated with a minimum
      2-year follow-up from January 2005 through August 2009. Confirmation of DM was
      performed by histopathology or follow-up imaging. Univariate and multivariate
      analyses were used for factors predictive of DM. The survival of patients was
      calculated by the Kaplan-Meier method. RESULTS: Thirty-six of the 404 eligible
      patients (8.9%) developed DM, most frequently in the lungs (80.6%). Univariate
      analyses revealed that T and N classifications, lymphovascular invasion and
      perineural invasion of the primary tumor, and locoregional recurrences were each
      significantly associated with the development of DM (P < .05). Multivariate
      analyses showed that T and N classifications and locoregional recurrences were
      independent predictors of DM (P < .05). The overall 1- and 2-year survival rates
      of the 36 patients with DMs were 40.6% and 13.5%, respectively. Metastases to
      more than 1 organ negatively affected patient survival (P < .001). CONCLUSION:
      Patients with advanced tumors, nodal involvement, or locoregional recurrences may
      require more frequent surveillance for the development of DMs.

PMID- 22581638
TI  - Association of cadherin23 single nucleotide polymorphism with age-related hearing
      impairment in Han Chinese.
AB  - OBJECTIVE: Genetic variation of cadheri23 (cdh23; 753G>A in exon 7) has been
      implicated with age-related hearing impairment (ARHI) in mice. This study aimed
      to test the association of the CDH23 tag single nucleotide polymorphism (SNP) in
      intron 7 with ARHI in Han Chinese. STUDY DESIGN: Individual cohort study.
      SETTING: Tertiary medical center. SUBJECTS AND METHODS: A total of 1175 Han
      Chinese subjects were divided into the case group (n = 310, 26% with poorest
      hearing) and the control group (n = 308, the 26% with best hearing) according to
      the Z(high) score converted from the original frequency-specific hearing
      thresholds. The CDH23 SNP locus (rs7087735: C/T) in intron 7 (coordinate:
      72996763) shown in the HapMap was genotyped with correlation to the hearing
      phenotype. RESULTS: The genotype distributions of CDH23 (CC/CT/TT) were not
      significantly different between the case and control group (P = .489). Compared
      with genotype CC, the odds ratios of the genotypes CT and TT for ARHI were not
      significantly different after adjustment for other environmental factors (P =
      .299 for CT; P = .610 for TT). CONCLUSIONS: Despite that the Ahl allele of Cdh23
      had been implicated with ARHI in mice, we found no positive association of the
      CDH23 tag SNP in intron 7 with ARHI in Han Chinese.

PMID- 22581639
TI  - Surveillance low-dose chest computed tomography for head and neck cancer
      patients.
AB  - Based on the recent results of the National Lung Cancer Screening Trial, the
      National Comprehensive Cancer Network now recommends annual screening with low
      dose computed tomography for high-risk individuals (generally defined as 45- to
      60-year-old current or former smokers). As head and neck cancer patients are at a
      high risk for (second) lung cancers, annual surveillance computed tomography
      should be considered for head and neck cancer patients.

PMID- 22581640
TI  - Expanding the phenotypic and mutational spectrum in microcephalic osteodysplastic
      primordial dwarfism type I.
AB  - Mutations in the RNU4ATAC gene cause microcephalic osteodysplastic primordial
      dwarfism type I. It encodes U4atac, a small nuclear RNA that is a component of
      the minor spliceosome. Six distinct mutations in 30 patients diagnosed as
      microcephalic osteodysplastic primordial dwarfism type I have been described. We
      report on three additional patients from two unrelated families presenting with a
      milder phenotype of microcephalic osteodysplastic primordial dwarfism type I and
      metopic synostosis. Patient 1 had two novel heterozygous mutations in the 3'
      prime stem-loop, g.66G > C and g.124G > A while Patients 2 and 3 had a homozygous
      mutation g.55G > A in the 5' prime stem-loop. Although they manifested the known
      spectrum of clinical features of microcephalic osteodysplastic primordial
      dwarfism type I, they lacked evidence of severe developmental delay and
      neurological symptoms. These findings expand the mutational and phenotypic
      spectrum of this syndrome.

PMID- 22581641
TI  - First annual meeting of the EpiGeneSys Network of Excellence: moving epigenetics
      towards systems biology.
AB  - This meeting united participants from the fields of experimental epigenetics,
      mathematics and computational biology, to discuss results and challenges in the
      endeavour to explore points of synergy between these fields. The design shown
      here expresses the idea of moving complex biological phenomena (left nucleosome)
      towards precise mathematical descriptions (right nucleosome).

PMID- 22581642
TI  - HIF1A induces expression of the WASF3 metastasis-associated gene under hypoxic
      conditions.
AB  - The WASF3 (WAVE3) gene is an important mediator of cell motility, invasion and
      metastasis and is expressed at high levels in some advanced stage tumors. In our
      survey of breast cancer cells, we now demonstrate that exposure to hypoxic
      conditions increases WASF3 expression levels in MDA231, SKBR3 and MCF7 cells. The
      WASF3 promoter region contains HIF1A response elements (HRE). ChIP assays
      demonstrate that HIF1A binds to these HRE elements in the promoter region, and
      luciferase reporter assays using the WASF3 gene minimal promoter shows that
      hypoxia results in its upregulation. Phosphorylation of WASF3 is required for its
      ability to affect invasion and increased phosphoactivation of WASF3 is also seen
      in cells challenged with hypoxia. These cells also show increased motility in the
      scratch wound assay. Cells in which WASF3 has been knocked down show no response
      to hypoxia as expected, implicating the specificity of the hypoxic response to
      WASF3. Overall, these experiments demonstrate WASF3 is a HIF1A-regulated gene and
      suggests a mechanism to explain the observation of elevated expression of WASF3
      in advanced stage tumors.

PMID- 22581643
TI  - Scoring protein interaction decoys using exposed residues (SPIDER): a novel
      multibody interaction scoring function based on frequent geometric patterns of
      interfacial residues.
AB  - Accurate prediction of the structure of protein-protein complexes in
      computational docking experiments remains a formidable challenge. It has been
      recognized that identifying native or native-like poses among multiple decoys is
      the major bottleneck of the current scoring functions used in docking. We have
      developed a novel multibody pose-scoring function that has no theoretical limit
      on the number of residues contributing to the individual interaction terms. We
      use a coarse-grain representation of a protein-protein complex where each residue
      is represented by its side chain centroid. We apply a computational geometry
      approach called Almost-Delaunay tessellation that transforms protein-protein
      complexes into a residue contact network, or an undirectional graph where vertex
      residues are nodes connected by edges. This treatment forms a family of
      interfacial graphs representing a dataset of protein-protein complexes. We then
      employ frequent subgraph mining approach to identify common interfacial residue
      patterns that appear in at least a subset of native protein-protein interfaces.
      The geometrical parameters and frequency of occurrence of each "native" pattern
      in the training set are used to develop the new SPIDER scoring function. SPIDER
      was validated using standard "ZDOCK" benchmark dataset that was not used in the
      development of SPIDER. We demonstrate that SPIDER scoring function ranks native
      and native-like poses above geometrical decoys and that it exceeds in performance
      a popular ZRANK scoring function. SPIDER was ranked among the top scoring
      functions in a recent round of CAPRI (Critical Assessment of PRedicted
      Interactions) blind test of protein-protein docking methods.

PMID- 22581644
TI  - Charge-conversional poly(amino acid)s derivatives as a drug delivery carrier in
      response to the tumor environment.
AB  - A charge-converting and pH-dependent nanocarrier was achieved by conjugating 2,3
      dimethylmaleic anhydride (DMMA) to the amino group of an octadecyl grafted poly
      (2-hydroxyethyl aspartamide) (PHEA-g-C(18)-NH(2)) backbone, thereby forming a
      spherical micelle. PHEA, a poly(amino acid)s derivative, was derived from
      poly(succinimide), which is biocompatible and biodegradable. DMMA, a detachable
      component at the tumor site, was added, preventing aggregation with negative
      blood serum and enhancing the nanocarrier's cellular uptake. The polymeric
      micelle was comprehensively characterized and doxorubicin was encapsulated
      successively. The cellular uptake and anticancer therapeutic effect were
      evaluated by flow cytometry, confocal laser scanning microscopy, and a MTT assay.
      The properties of the nanocarrier can further be exploited to develop an early
      detection module for cancer. The present work is also expected to advance the
      study of designing smart carriers for drug and gene delivery.

PMID- 22581645
TI  - Isolation and characterization of a phenol-degrading Rhodococcus sp. strain
      AQ5NOL 2 KCTC 11961BP.
AB  - In this work, we report on the isolation of a phenol-degrading Rhodococcus sp.
      with a high tolerance towards phenol. The isolate was identified as Rhodococcus
      sp. strain AQ5NOL 2, based on 16S rDNA analysis. The strain degraded phenol using
      the meta pathway, a trait shared by many phenol-degraders. In addition to phenol
      biodegradation, the strain was also capable of degrading diesel. Strain AQ5NOL 2
      exhibited a broad optimum temperature for growth on phenol at between 20  degrees
      C and 35  degrees C. The best nitrogen sources were ammonium sulphate, glycine or
      phenylalanine, followed by proline, nitrate, leucine, and alanine (in decreasing
      efficiency). Strain AQ5NOL 2 showed a high tolerance and degradation capacity of
      phenol, for it was able to register growth in the presence of 2000 mg l(-1)
      phenol. The growth of this strain on phenol as sole carbon and energy source were
      modeled using Haldane kinetics with a maximal specific growth rate (MU(max)) of
      0.1102 hr(-1), a half-saturation constant (K(s) ) of 99.03 mg l(-1) or 1.05 mmol
      l(-1), and a substrate inhibition constant (K(i)) of 354 mg l(-1) or 3.76 mmol l(
      1). Aside from phenol, the strain could utilize diesel, 2,4-dinitrophenol and rho
      cresol as carbon sources for growth. Strain AQ5NOL 2 exhibited inhibition of
      phenol degradation by Zn(2+), Cu(2+), Cr(6+), Ag(+) and Hg(2+) at 1 mg l(-1).

PMID- 22581647
TI  - High circulating sclerostin is present in patients with thalassemia-associated
      osteoporosis and correlates with bone mineral density.
AB  - Osteoporosis is a severe complication of thalassemia. Sclerostin is a Wnt
      signaling inhibitor, which is produced by osteocytes and inhibits osteoblast
      function. Sclerostin is implicated in the pathogenesis of osteoporosis of
      different etiology. The aim of the study was to evaluate circulating sclerostin
      in 66 patients (median age 42 years) with thalassemia and osteoporosis who
      participated in a phase 2, randomized study (zoledronic acid vs. placebo) and the
      results were compared with those of 30 healthy controls (median age 44 years)
      without osteopenia/osteoporosis and 62 women with postmenopausal osteoporosis
      (median age 63 years). At baseline, thalassemic patients with osteoporosis had
      elevated circulating levels of sclerostin (median: 605 pg/ml, range: 22-1,227
      pg/ml) compared to healthy controls without osteopenia/osteoporosis (250 pg/ml, 0
      720 pg/ml, p<0.001) and reduced levels of sclerostin compared with postmenopausal
      women with osteoporosis (840 pg/ml, 181-1,704 pg/ml, p<0.001). Thalassemia
      patients had also increased serum dickkopf-1 (Dkk-1) and high bone turnover.
      Circulating sclerostin levels correlated with bone mineral density in lumbar
      spine (r=0.619, p<0.001), distal radius (r=0.401, p=0.001) and femoral neck
      (r=0.301, p=0.021). Zoledronic acid did not alter sclerostin levels after 12
      months of therapy, although it reduced circulating Dkk-1. We conclude that
      circulating sclerostin is elevated in thalassemia patients with osteoporosis and
      correlated with their BMD, but it was not reduced post zoledronic acid
      administration. These findings suggest that high sclerostin may serve as a marker
      of increased osteocyte activity in thalassemia patients. Drugs targeting
      sclerostin may also be used in this difficult to treat disorder associated with
      bone loss.

PMID- 22581648
TI  - Glucose-dependent insulinotropic polypeptide (GIP) inhibits signaling pathways of
      advanced glycation end products (AGEs) in endothelial cells via its antioxidative
      properties.
AB  - Glucose-dependent insulinotropic polypeptide (GIP) is one of the incretins, a gut
      hormone secreted from K cells in the intestine in response to food intake. It
      could be a potential therapeutic target for the treatment of patients with type 2
      diabetes. However, effects of GIP on vascular injury remain unknown. Since
      interaction of advanced glycation end products (AGEs) with their receptor RAGE
      has been shown to play a crucial role in vascular damage in diabetes, this study
      investigated whether and how GIP blocked the deleterious effects of AGEs on human
      umbilical vein endothelial cells (HUVECs). GIP receptor was expressed in HUVECs.
      GIP, an analogue of cyclic AMP or inhibitors of NADPH oxidase inhibited the AGE
      induced reactive oxygen species (ROS) generation in HUVECs. Furthermore, GIP
      reduced both RAGE mRNA and protein levels in HUVECs. GLP-1 also blocked the AGE
      induced increase in mRNA levels of vascular cell adhesion molecule-1 (VCAM-1) and
      plasminogen activator inhibitor-1 in HUVECs. In addition, an antioxidant N
      acetylcysteine mimicked the effects of GIP on RAGE and VCAM-1 gene expression in
      HUVECs. Our present study suggests that GIP could block the signal pathways of
      AGEs in HUVECs by reducing ROS generation and subsequent RAGE expression probably
      via GIP receptor-cyclic AMP axis.

PMID- 22581646
TI  - Sex, stress, and mood disorders: at the intersection of adrenal and gonadal
      hormones.
AB  - The risk for neuropsychiatric illnesses has a strong sex bias, and for major
      depressive disorder (MDD), females show a more than 2-fold greater risk compared
      to males. Such mood disorders are commonly associated with a dysregulation of the
      hypothalamo-pituitary-adrenal (HPA) axis. Thus, sex differences in the incidence
      of MDD may be related with the levels of gonadal steroid hormone in adulthood or
      during early development as well as with the sex differences in HPA axis
      function. In rodents, organizational and activational effects of gonadal steroid
      hormones have been described for the regulation of HPA axis function and, if
      consistent with humans, this may underlie the increased risk of mood disorders in
      women. Other developmental factors, such as prenatal stress and prenatal
      overexposure to glucocorticoids can also impact behaviors and neuroendocrine
      responses to stress in adulthood and these effects are also reported to occur
      with sex differences. Similarly, in humans, the clinical benefits of
      antidepressants are associated with the normalization of the dysregulated HPA
      axis, and genetic polymorphisms have been found in some genes involved in
      controlling the stress response. This review examines some potential factors
      contributing to the sex difference in the risk of affective disorders with a
      focus on adrenal and gonadal hormones as potential modulators. Genetic and
      environmental factors that contribute to individual risk for affective disorders
      are also described. Ultimately, future treatment strategies for depression should
      consider all of these biological elements in their design.

PMID- 22581649
TI  - PDE4 control on cAMP/PKA compartmentation revealed by biosensor imaging in
      neurons.
AB  - Electrophysiological recordings (using the slow-AHP potassium current) together
      with novel biosensor imaging methods (with AKAR and Epac sensors) were used in
      preparations of rodent brain slices to record PKA activation in real time and in
      individual neurons. The experiments revealed the propagation of the PKA signal
      from the membrane to the cytosol and eventually to the nucleus. The experiments
      show how the geometry of the neurons combined with phosphodiesterase activities
      (mostly rolipram-sensitive PDE4) contributes to a functional compartmentation of
      the cAMP in subcellular domains.

PMID- 22581651
TI  - 3,4-dihydroxy-L-phenylalanine as a cell adhesion molecule in serum-free cell
      culture.
AB  - In this article, we examined the feasibility of using 3,4-dihydroxy-L
      phenylalanine (DOPA) as a cell adhesion molecule in serum-free cultures of
      anchorage-dependent mammalian cells. DOPA is a critical, functional element in
      mussel adhesive proteins and is known to bind strongly to various natural or
      synthetic materials. DOPA coating on culture plates was confirmed using X-ray
      photoelectron spectroscopy and energy-dispersive spectroscopy. Human dermal
      fibroblasts (HDFs) were cultured on DOPA-coated, fibronectin-coated, or no
      material-coated culture plates in serum-free medium. HDFs cultured on DOPA showed
      the highest cell adhesion ratio, spreading, and viability but the lowest
      apoptotic activity. Therefore, DOPA may be a useful cell-adhesion molecule for
      serum-free culture.

PMID- 22581652
TI  - Challenges in cardiac resynchronization therapy-defibrillator upgrade in a
      patient with right pneumonectomy.

PMID- 22581653
TI  - Paralogous annotation of disease-causing variants in long QT syndrome genes.
AB  - Discriminating between rare benign and pathogenic variation is a key challenge in
      clinical genetics, particularly as increasing numbers of nonsynonymous single
      nucleotide polymorphisms (SNPs) are identified in resequencing studies. Here, we
      describe an approach for the functional annotation of nonsynonymous variants that
      identifies functionally important, disease-causing residues across protein
      families using multiple sequence alignment. We applied the methodology to long QT
      syndrome (LQT) genes, which cause sudden death, and their paralogues, which
      largely cause neurological disease. This approach accurately classified known LQT
      disease-causing variants (positive predictive value = 98.4%) with a better
      performance than established bioinformatic methods. The analysis also identified
      1078 new putative disease loci, which we incorporated along with known variants
      into a comprehensive and freely accessible long QT resource
      (http://cardiodb.org/Paralogue_Annotation/), based on newly created Locus
      Reference Genomic sequences (http://www.lrg-sequence.org/). We propose that
      paralogous annotation is widely applicable for Mendelian human disease genes.

PMID- 22581654
TI  - Familial Xp22.33-Xp22.12 deletion delineated by chromosomal microarray analysis
      causes proportionate short stature.
AB  - Patients with Xp deletions have short stature and may have some somatic traits
      typical of Turner syndrome (TS), whereas gonadal function is generally preserved.
      In most studies of these patients, microsatellites have been used to determine
      the break point of the Xp deletion. In the present study, we describe the
      clinical, cytogenetic, and chromosomal microarray (CMA) analysis of a family with
      an Xp22.33-Xp22.12 deletion. Two female siblings, aged 8 years 9 months and 11
      years 10 months, presented with short stature. The older sibling's height (index
      case) was 137.9 cm (-1.81 SDS) and the younger sibling's height was 118.6 cm (
      2.13 SDS). The mother and both daughters had only a short stature; a skeletal
      survey showed normal findings except for mildly shortened 4th and 5th metacarpal
      bones. No features of TS were present. The deletion appeared terminal with a
      breakpoint within Xp22.2 located about 19.9 Mb from the Xp telomere. The deletion
      contained 102 protein-coding genes. A probe of the end breakage point was located
      at the 19,908,986th base of the X chromosome, and a probe of the marginal normal
      region near the breakage point was located at the 19,910,848th base of the X
      chromosome. Therefore, the breakage point was concluded to be located between
      these two probes. In summary, we report a familial case of an Xp deletion. The
      findings of our study may be helpful in further analyzing the phenotypes
      associated with Xp deletions.

PMID- 22581655
TI  - Enantioselective separations using chiral supported liquid crystalline membranes.
AB  - Porous and nonporous supported liquid crystalline membranes were produced by
      impregnating porous cellulose nitrate supports with cholesteric liquid crystal
      (LC) materials consisting of 4-cyano-4'-pentylbiphenyl (5CB) mixed with a
      cholesterol-based dopant (cholesteryl oleyl carbonate [COC], cholesteryl
      nonanoate [CN], or cholesteryl chloride [CC]). The membranes exhibit selectivity
      for R-phenylglycine and R-1-phenylethanol because of increased interactions
      between the S enantiomers and the left-handed cholesteric phase. The selectivity
      of both phenylglycine and 1-phenylethanol in 5CB/CN membranes decreases with
      effective pore diameter while the permeabilities increase, as expected.
      Phenylglycine, which is insoluble in the LC phase, exhibits no transport in the
      nonporous (completely filled) membranes; however, 1-phenylethanol, which is
      soluble in the LC phase, exhibits transport but negligible enantioselectivity.
      The enantioselectivity for 1-phenylethanol was higher (1.20 in 5CB/COC and 5CB/CN
      membranes) and the permeability was lower in the cholesteric phase than in the
      isotropic phase. Enantioselectivity was also higher in the 5CB/COC cholesteric
      phase than in the nematic phase of undoped 5CB (1.03). Enantioselectivity in the
      cholesteric phase of 5CB doped with CC (1.1), a dopant lacking hydrogen bonding
      groups, was lower than in the 5CB/COC phases. Finally, enantioselectivity
      increases with the dopant concentration up to a plateau value at approximately 17
      mol%.

PMID- 22581656
TI  - Targeted therapy for triple-negative breast cancer: where are we?
AB  - Breast cancers that are negative for estrogen receptor (ER), progesterone
      receptors (PR) and HER2, using standard clinical assays, have been dubbed triple
      negative (TN). Unlike other molecular subtypes of invasive breast cancer,
      validated targeted therapies are currently unavailable for patients with TN
      breast cancer. Preclinical studies however, have identified several potential
      targets such as epidermal growth factor receptor (EGFR), SRC, MET and poly ADP
      ribose polymerase 1/2 (PARP1/2). Because of tumor heterogeneity, it is unlikely
      that any single targeted therapy will be efficacious in all patients with TN
      breast cancer. The rational way forward for treating these patients is likely to
      be biomarker-driven, combination targeted therapies or combination of targeted
      therapy with cytotoxic chemotherapy.

PMID- 22581657
TI  - Indirect coating of RGD peptides using a poly-L-lysine spacer enhances jaw
      periosteal cell adhesion, proliferation, and differentiation into osteogenic
      tissue.
AB  - The aim of our study was to generate a biofunctionalized, three-dimensional (3D)
      biomaterial to enhance jaw periosteal cell (JPC) adhesion and differentiation
      into osteogenic tissue. Therefore, open-cell polylactic acid (OPLA) scaffolds
      were coated covalently with different RGD peptides (a conserved recognition
      sequence of the most ECM proteins--arginine-glycine-asparagine) and different
      coating variants. The linear and cyclic RGD peptides were either applied directly
      or indirectly via a poly-L-lysine (PLL) spacer. JPCs were analyzed on coated
      constructs in 2D and 3D cultures and showed enhanced rates for indirectly coated
      scaffolds using the PLL spacer. By gene expression, we detected significantly
      increased levels of osteogenic marker genes, such as alkaline phosphatase, RUNX2,
      and AMELY in JPCs seeded onto PLL/linear RGD constructs compared to the otherwise
      coated constructs. An analysis of the JPC mineralization capacity revealed the
      highest amounts of calcium-phosphate precipitates in cells growing within the
      PLL/linear scaffolds. Additionally, the JPC adhesion behavior on OPLA scaffolds
      seems to be mediated by ITGB3, ITGB1, and ITGAV, as shown by blocking assays. We
      concluded that coating of OPLA constructs with linear RGD peptides via PLL
      represents a suitable approach for functionalizing the polymer surface and
      enhancing adhesion, proliferation, and mineralization of JPCs.

PMID- 22581658
TI  - Compensatory enlargement of a solitary functioning kidney during fetal
      development.
AB  - OBJECTIVE: To determine the degree of compensatory enlargement, and its time of
      onset, of the solitary functioning kidney (SFK) in fetuses with unilateral renal
      agenesis (URA) or unilateral multicystic kidney dysplasia (MCKD). METHODS: This
      was a retrospective study of fetuses with URA or MCKD diagnosed prenatally and
      confirmed postnatally in the period from January 1999 to May 2011. Fetuses with
      any other congenital anomalies were excluded. Measurements of kidney length were
      retrieved from our prenatal ultrasound database and a nomogram was established
      and compared with that for normal kidney length. RESULTS: In total, 67 fetuses
      were identified, 60 with MCKD and seven with URA, for which we obtained 147
      kidney length measurements from our database. Mean gestational age at time of
      measurement was 29.7 (range, 18.4-36.7) weeks. Compensatory enlargement, defined
      as renal length >95(th)  percentile for gestational age, was demonstrated in 87%
      of the MCKD cases and 100% of the URA cases (88% of cases overall). We estimated
      the mean enlargement for an SFK (defined as difference from 50(th)  percentile
      for normal renal length) at 36 weeks' gestation to be 23.1% (9.25 mm), with the
      mean value being 11.4% (5.04 mm) greater than the 95(th)  percentile for a normal
      kidney at this gestational age. Compensatory enlargement of SFKs was evident from
      the 20(th)  week of gestation onwards. CONCLUSION: Compensatory enlargement of
      SFKs occurs in almost 90% of fetuses with MCKD or URA, and may be observed from
      the 20(th)  week of gestation onwards.

PMID- 22581659
TI  - Retracted publications in the drug literature.
AB  - Recent studies have suggested an increase in the number of retracted scientific
      publications. It is unclear how broadly the issue of misleading and fraudulent
      publications pertains to retractions of drug therapy studies. Therefore, we
      sought to determine the trends and factors associated with retracted publications
      in drug therapy literature. A PubMed search was conducted to identify retracted
      drug therapy articles published from 2000-2011. Articles were grouped according
      to reason for retraction, which was classified as scientific misconduct or error.
      Scientific misconduct was further divided into data fabrication, data
      falsification, questions of data veracity, unethical author conduct, and
      plagiarism. Error was defined as duplicate publication, scientific mistake,
      journal error, or unstated reasons. Additional data were extracted from the
      retracted articles, including type of article, funding source, author
      information, therapeutic area, and retraction issue. A total of 742 retractions
      were identified from 2000-2011 in the general biomedical literature, and 102 drug
      studies met our inclusion criteria. Of these, 73 articles (72%) were retracted
      for a reason classified as scientific misconduct, whereas 29 articles (28%) were
      retracted for error. Among the 73 articles classified as scientific misconduct,
      those classified as unethical author conduct (32 articles [44%]) and data
      fabrication (24 articles [33%]) constituted the majority. The median time from
      publication of the original article to retraction was 31 months (range 1-130).
      Fifty percent of retracted articles did not state a funding source, whereas
      pharmaceutical manufacturer funding accounted for only 13 articles (13%)
      analyzed. Many retractions were due to repeat offenses by a small number of
      authors, with nearly 40% of the retracted studies associated with two
      individuals. We found that a greater proportion of drug therapy articles were
      retracted for reasons of misconduct and fraud compared with other biomedical
      studies. It is important for health care practitioners to monitor the literature
      for retractions so that recommendations for drug therapy and patient management
      may be modified accordingly.

PMID- 22581661
TI  - Preliminary investigation of residual limb plantarflexion and dorsiflexion muscle
      activity during treadmill walking for trans-tibial amputees.
AB  - BACKGROUND: Novel powered prosthetic ankles currently incorporate finite state
      control, using kinematic and kinetic sensors to differentiate stance and swing
      phases/sub-phases and control joint impedance and position or torque. For more
      intuitive control, myoelectric control of the ankle using the remnant residual
      limb dorsiflexors and plantarflexors, perhaps in concert with kinetic and
      kinematic sensors, may be possible. OBJECTIVE: The specific research objective
      was to assess the feasibility of using myoelectric control of future active or
      powered prosthetic ankle joints for trans-tibial amputees. STUDY DESIGN: The
      project involved human subject trials to determine whether current techniques of
      myoelectric control of upper extremity prostheses might be readily adapted for
      lower extremity prosthetic control. METHODS: Gait analysis was conducted for
      three unilateral trans-tibial amputee subjects during ambulation on an
      instrumented split belt treadmill. Data included ankle plantarflexor and
      dorsiflexor activity for the residual limb, as well as lower limb kinematics and
      ground reaction forces and moments of both the sound and prosthetic limbs.
      RESULTS: These data indicate that: 1) trans-tibial amputees retain some
      independent ankle plantarflexor and dorsiflexor muscle activity of their residual
      limb; 2) it is possible to position surface electromyographic electrodes within a
      trans-tibial socket that maintain contact during ambulation; 3) both the
      plantarflexors and dorsiflexors of the residual limb are active during gait; 4)
      plantarflexor and dorsiflexor activity is consistent during multiple gait cycles;
      and 5) with minimal training, trans-tibial amputees may be able to activate their
      plantarflexors during push-off. CONCLUSIONS: These observations demonstrate the
      potential for future myoelectric control of active prosthetic ankles. Clinical
      relevance This study demonstrated the feasibility of applying upper extremity
      prosthetic myoelectric signal acquisition, processing and control techniques to
      future myoelectric control of active prosthetic ankles for trans-tibial amputees.

PMID- 22581662
TI  - [First clinical experiences with an endoscope manipulator system in endo- and
      transnasal surgery].
AB  - BACKGROUND: Endo- and transnasal surgery needs optical support. The use of a
      microscope allows bimanual manipulation. More often the endoscopic technique is
      used which needs one hand for endoscope guidance "loosing" it for manipulation or
      demanding an assistant for endoscope guidance. In this work the use of a
      miniature endoscope manipulator system for endonasal and transnasal surgery was
      evaluated. MATERIAL AND METHODS: 31 FESS with manipulator-assisted endoscope
      guidance were performed. The used endoscope positions, the number of position
      changes and conditional interruptions were documented. In addition, a
      transsphenoidal approach to the pituitary gland was performed in a cadaver trial.
      RESULTS: Non-inferiority was shown for the use of the endoscope manipulator with
      reference to time and accuracy of manipulator-assisted endoscope guidance. There
      were 6.4 position changes for each side. Bimanual manipulation was possible in
      all cases. In the region of high-risk structures (lamina papyracea, frontal
      recess) we conceptual switched to manual endoscope guidance. CONCLUSION: The
      evaluated endoscope manipulator fulfills the minimum requirements to be
      integrated into the surgical workflow of endo- and transnasal surgery. The number
      of required endoscope position changes is small allowing bimanual
      instrumentation. Still a disadvantage is the need for interrupting the workflow
      to remote the endoscope manipulator with the joystick console. Further
      development potential would be a forced-feedback function and hands-free
      navigated-controlled guidance.

PMID- 22581663
TI  - [First experience in endonasal surgery using a new 3D-Chipendoscope].
AB  - BACKGROUND: Endoscopic surgery for treatment of nasal, paranasal and anterior
      skull base pathologies is an established treatment modality. Available rigid
      endoscopes with angled views provide a 2-dimensional view with restriction of
      depth perception. In this study we report about our first experience with a new
      3D-Chipendoscope in surgery at the nose, paranasal sinuses und anterior skull
      base. MATERIAL AND METHODS: 30 patients were enrolled in this study with chronic
      rhinosinusitis, inverted papilloma, frontal sinus mucocele, frontal sinus
      osteoma, chronic dacryocystitis and pituitary adenoma. All patients were
      subjected to standard endonasal endoscopic surgery using 3D-endoscopes. RESULTS:
      Surgery was performed by the use of the 3D-endoscope in all patients. The
      operative handling of the 3D-endoscopes was user friendly in regard to design and
      weight of the endoscopes. The problem of fogging during endoscopic surgery
      diminishing the quality of view was not observed. Blood crusts on the endoscope
      tip however was able to changed the 3D-view to a 2D-view. To close positioning of
      the 3D-endoscopes to the surgical field reduced image quality. The visualisation
      of the frontal sinus was limited. CONCLUSION: 3D-endoscopic surgery is an
      interesting development in endonasal surgery of pathologies at the nose,
      paranasal sinuses and anterior skull base.

PMID- 22581664
TI  - Expression of chitinase genes of Metarhizium anisopliae isolates in lepidopteran
      pests and on synthetic media.
AB  - Pathogenecity of the well characterized entomopathogenic fungus Metarhizium
      anisopliae used for biocontrol of a wide range of insect pests secretes
      hydrolytic enzymes that degrade the host cuticle. The chitinolytic activity of
      high and low virulent isolates of M. anisopliae was assayed on minimal medium
      (MM) + colloidal chitin and MM supplemented with insect cuticles. Ex- pression
      pattern of four chitinase genes (chitinase (chi), chi 1, chi 2, chi 3) was
      profiled during pathogenic stages of the entomopathogen under in vitro and in
      vivo conditions. Reverse-transcription polymerase chain reaction (RT-PCR)
      analysis confirmed that chitinase cDNAs were expressed during the germination of
      fungus under nutrient-deprived conditions. RT-PCR analysis performed for the four
      chitinase genes on the two insect hosts Spodoptera litura and Helicoverpa
      armigera at six developmental stages of the pathogen displayed up-regulation in
      S. litura at mycosed and conidiated condition while with H. armigera there was
      expression only after 48 h of incubation. Differential expression of chi, chi 1
      and chi 2 genes in vitro (nitrogen rich and nitrogen limiting media) and in vivo
      (live insect hosts S. litura and H. armigera) implicate the role of substrate
      differences in pathogenesis.

PMID- 22581665
TI  - The lactate conundrum in wound healing: clinical and experimental findings
      indicate the requirement for a rapid point-of-care diagnostic.
AB  - The increasing prevalence of chronic wounds has significant financial
      implications for nations with advanced healthcare provision. Although the
      diseases that predispose to hard-to-heal wounds are recognized, their etiology is
      less well understood, partly because practitioners in wound management lack
      specialized diagnostic support. Prognostic indicators for healing may be inherent
      to wound biochemistry but remain invisible under routine clinical investigation;
      lactate is an example of this. In this study, lactate concentration in exudate
      obtained from 20 patients undergoing wound management in hospital was variable
      but in some cases approached or exceeded 20 mM. In vitro viability studies
      indicated that fibroblasts and endothelial cells tolerated low levels of lactate
      (1-10 mM), but cell viability was severely compromised by high lactate
      concentrations (=20 mM). Scratched monolayer experiments revealed that cell
      migration was affected earlier than viability in response to increasing lactate
      dose, and this was shown by immunocytochemistry to be associated with
      cytoskeletal disruption. A prototype enzyme-based colorimetric assay for lactate
      generating a color change that was rapid in the context of clinical practise, and
      capable of functioning within a gel vehicle, was developed with point-of-care
      dipstick applications in mind. A randomized single-blinded trial involving 30
      volunteers and using a color chart to calibrate the assay demonstrated that
      lactate concentration could be reliably estimated with 5 mM precision; this
      suggesting that "physiological" and "pathological" lactate concentration could be
      distinguished. The present data suggest that a dipstick-type colorimetric assay
      could comprise a viable diagnostic tool for identifying patients at-risk from
      high-wound lactate.

PMID- 22581666
TI  - Enantioselective degradation of indoxacarb in cabbage and soil under field
      conditions.
AB  - The enantioselective degradation of indoxacarb in cabbage and soil has been
      investigated in Beijing and Anhui under open conditions. Indoxacarb enantiomers
      in samples were extracted with acetonitrile, cleaned up by florisil SPE column,
      separated on high performance liquid chromatography with a cellulose-tris-(3, 5
      dimethylphenylcarbamate)-based chiral stationary phase (CDMPC-CSP), and
      determined by a photodiode array detector. The validation of the developed method
      by fortification rac-indoxcarb in cabbage and soil showed good accuracy and
      precision. The results of field trials indicated that the dissipation of
      indoxacarb enantiomers followed pseudo-first-order kinetics or first-order
      kinetics in cabbage and soil at two locations. The half-lives of two enantiomers
      in cabbage ranged from 2.8 to 4.6 d which were shorter than those in soil ranging
      from 23 to 35 d. The changes of enantiomeric fraction values proved that
      enantioselective degradation of indoxacarb happened in cabbage and soil. The (-)
      indoxacarb showed faster degradation in the Beijing cabbage, whereas in the Anhui
      cabbage, (+)-indoxacarb preferentially degraded. In soil, preferential
      degradation of (+)-indoxacarb was observed at two locations.

PMID- 22581667
TI  - Inactive matriptase-2 mutants found in IRIDA patients still repress hepcidin in a
      transfection assay despite having lost their serine protease activity.
AB  - Mutations of the TMPRSS6 gene, which encodes Matriptase-2, are responsible for
      iron-refractory iron-deficiency anemia. Matriptase-2 is a transmembrane protease
      that downregulates hepcidin expression. We report one frameshift
      (p.Ala605ProfsX8) and four novel missense mutations (p.Glu114Lys, p.Leu235Pro,
      p.Tyr418Cys, p.Pro765Ala) found in IRIDA patients. These mutations lead to
      changes in both the catalytic and noncatalytic domains of Matriptase-2. Analyses
      of the mutant proteins revealed a reduction of autoactivating cleavage and the
      loss of N-Boc-Gln-Ala-Arg-p-nitroanilide hydrolysis. This resulted either from a
      direct modification of the active site or from the lack of the autocatalytic
      cleavage that transforms the zymogen into an active protease. In a previously
      described transfection assay measuring the ability of Matriptase-2 to repress the
      hepcidin gene (HAMP) promoter, all mutants retained some, if not all, of their
      transcriptional repression activity. This suggests that caution is called for in
      interpreting the repression assay in assessing the functional relevance of
      Matriptase-2 substitutions. We propose that Matriptase-2 activity should be
      measured directly in the cell medium of transfected cells using the chromogenic
      substrate. This simple test can be used to determine whether a sequence variation
      leading to an amino acid substitution is functionally relevant or not.

PMID- 22581668
TI  - Germline mosaicism in Cornelia de Lange syndrome.
AB  - Cornelia de Lange syndrome (CdLS) is a genetic disorder associated with delayed
      growth, intellectual disability, limb reduction defects, and characteristic
      facial features. Germline mosaicism has been a described mechanism for CdLS when
      there are several affected offspring of apparently unaffected parents. Presently,
      the recurrence risk for CdLS has been estimated to be as high as 1.5%; however,
      this figure may be an underrepresentation. We report on the molecularly defined
      germline mosaicism cases from a large CdLS database, representing the first large
      case series on germline mosaicism in CdLS. Of the 12 families, eight have been
      previously described; however, four have not. No one specific gene mutation,
      either in the NIPBL or the SMC1A gene, was associated with an increased risk for
      germline mosaicism. Suspected or confirmed cases of germline mosaicism in our
      database range from a conservative 3.4% up to 5.4% of our total cohort. In
      conclusion, the potential reproductive recurrence risk due to germline mosiacism
      should be addressed in prenatal counseling for all families who have had a
      previously affected pregnancy or child with CdLS.

PMID- 22581670
TI  - Accuracy of concurrent visual and cytology screening in detecting cervical cancer
      precursors in rural India.
AB  - The high burden of cervical cancer and inadequate/suboptimal cytology screening
      in developing countries led to the evaluation of visual screening tests, like
      visual inspection with acetic acid (VIA) and Lugol's iodine (VILI). We describe
      the performance of VIA, VILI and cytology, carried out in a multinational project
      called "Screening Technologies to Advance Rapid Testing" in 5,519 women aged 30
      49 years, in detecting cervical intraepithelial neoplasia (CIN). VIA, VILI and
      cytology were positive in 16.9%, 15.6% and 6.1% women, respectively. We found 57
      cases of CIN2, 55 of CIN3 and 12 of cervical cancer; 90% of CIN3 and 43% CIN2
      cases were positive for p16 overexpression and high-risk HPV infection,
      indicating a high validity of histological diagnosis. The sensitivity of VIA,
      VILI and cytology to detect high-grade CIN were 64.5%, 64.5% and 67.7%,
      respectively; specificities were 84.2%, 85.5% and 95.4%. A high proportion of p16
      positive CIN 3 (93.8%) and 2 (76.9%) were positive on cytology compared with
      visual tests (68.8% and 53.8%, respectively) indicating a higher sensitivity of
      cytology to detect p16 positive high-grade CIN. However, the immediate
      availability of the results from the visual tests permits diagnosis and/or
      treatment to be performed in the same sitting, which can potentially reduce loss
      to follow-up when women must be recalled following positive cytology. Organizing
      visual screening services in low-resource countries may facilitate the gradual
      building of an infrastructure committed to screening allowing the eventual
      introduction of more sensitive, highly objective, reproducible and affordable
      human papillomavirus screening tests in future.

PMID- 22581669
TI  - Effect of macrophage classical (M1) activation on implant-adherent macrophage
      interactions with Staphylococcus epidermidis: A murine in vitro model system.
AB  - A model in vitro system was developed for eliciting classical (M1) activation of
      surface-adherent murine macrophages, which was then used to study the interaction
      of the M1 macrophages with Staphylococcus epidermidis. Glass substrata were first
      covalently grafted with a mixture of methoxy- and biotin-terminated silanated
      polyethylene glycol. Interferon (IFN)-gamma and/or lipopolysaccharide (LPS),
      ligands known to induce the highly microbicidal M1 activation state in
      macrophages, were biotinylated and immobilized by way of a streptavidin
      intermediate to the biotin-PEG base substratum. Assessment of mouse bone marrow
      derived macrophage (BMDM) interleukin (IL)-12(p40) and nitric oxide response to
      the fabricated surfaces confirmed that the model system achieved activation of
      adherent macrophage: IFN-gamma-presenting surfaces primed cells for M1
      activation, LPS-presenting surfaces elicited innate activation, and surface
      presenting a combination of IFN-gamma and LPS induced M1 activation. The
      phagocytic and microbicidal capacity of activated, surface-adherent BMDM was
      evaluated using S. epidermidis, a bacterial species prevalent in implant
      associated infections. Results indicate that M1 activation of implant-adherent
      macrophages trends towards diminishing their phagocytic capacity, but enhances
      their microbicidal capacity for S. epidermidis.

PMID- 22581671
TI  - Size and volume charts of fetal kidney, renal pelvis and adrenal gland.
AB  - OBJECTIVE: To establish reference curves for size and volume of the fetal kidney,
      renal pelvis and adrenal gland, as measured using ultrasound from the 15(th) 
      week of gestation. METHODS: This was a prospective, longitudinal study of 96
      fetuses in low-risk singleton pregnancies, in which we performed serial
      ultrasound examinations at 4-week intervals. The length and anteroposterior and
      transverse diameters of both kidneys, the anteroposterior and transverse
      diameters of the renal pelvises and the length of the adrenal glands were
      measured three times at each examination, with the average being used for further
      analysis. Reference charts were constructed using multilevel statistical analysis
      and comparisons were made with previously published charts derived from cross
      sectional data. RESULTS: We present nomograms for fetal kidney dimensions and
      volume, renal pelvis dimensions and adrenal gland length. The new charts show
      differences in shape and have narrower percentile bands in comparison to
      previously published reference ranges. CONCLUSIONS: These new charts of
      measurements of the fetal kidney, renal pelvis and adrenal gland, from a
      prospective, longitudinal study, may be useful in the diagnosis and assessment of
      pathology of the kidney and adrenal gland.

PMID- 22581673
TI  - Resveratrol and health: the starting point.
AB  - Cascade of youth? Resveratrol, the celebrated phytoalexin of red wine, was known
      to activate AMPK indirectly, but how this happened was unclear. In a paper
      recently published in Cell, S.-J. Park, J. H. Chung and co-workers identify the
      signalling cascade, which begins with the inhibition of phosphodiesterases, in
      particular PDE4. But questions remain, even while new perspectives open up.

PMID- 22581672
TI  - Neonatal exposure to antiepileptic drugs disrupts striatal synaptic development.
AB  - OBJECTIVE: Drug exposure during critical periods of brain development may
      adversely affect nervous system function, posing a challenge for treating
      infants. This is of particular concern for treating neonatal seizures, as early
      life exposure to drugs such as phenobarbital is associated with adverse
      neurological outcomes in patients and induction of neuronal apoptosis in animal
      models. The functional significance of the preclinical neurotoxicity has been
      questioned due to the absence of evidence for functional impairment associated
      with drug-induced developmental apoptosis. METHODS: We used patch-clamp
      recordings to examine functional synaptic maturation in striatal medium spiny
      neurons from neonatal rats exposed to antiepileptic drugs with proapoptotic
      action (phenobarbital, phenytoin, lamotrigine) and without proapoptotic action
      (levetiracetam). Phenobarbital-exposed rats were also assessed for reversal
      learning at weaning. RESULTS: Recordings from control animals revealed increased
      inhibitory and excitatory synaptic connectivity between postnatal day (P)10 and
      P18. This maturation was absent in rats exposed at P7 to a single dose of
      phenobarbital, phenytoin, or lamotrigine. Additionally, phenobarbital exposure
      impaired striatal-mediated behavior on P25. Neuroprotective pretreatment with
      melatonin, which prevents drug-induced neurodevelopmental apoptosis, prevented
      the drug-induced disruption in maturation. Levetiracetam was found not to disrupt
      synaptic development. INTERPRETATION: Our results provide the first evidence that
      exposure to antiepileptic drugs during a sensitive postnatal period impairs
      physiological maturation of synapses in neurons that survive the initial drug
      insult. These findings suggest a mechanism by which early life exposure to
      antiepileptic drugs can impact cognitive and behavioral outcomes, underscoring
      the need to identify therapies that control seizures without compromising
      synaptic maturation.

PMID- 22581674
TI  - Liquid-liquid extraction for recovery of paclitaxel from plant cell culture:
      solvent evaluation and use of extractants for partitioning and selectivity.
AB  - A major challenge in the production of metabolites by plant cells is the
      separation and purification of a desired product from a number of impurities. An
      important application of plant cell culture is the biosynthesis of the anticancer
      agent paclitaxel. Liquid-liquid extraction plays a critical role in the recovery
      of paclitaxel and other valuable plant-derived products from culture broth. In
      this study, the extraction of paclitaxel and a major unwanted by-product,
      cephalomannine, from plant cell culture broth into organic solvents is
      quantified. Potential solvent mixtures show varying affinity and selectivity for
      paclitaxel over cephalomannine. The partition coefficient of paclitaxel is
      highest in ethyl acetate and dichloromethane, with measured values of 28 and 25,
      respectively; however, selectivity coefficients are less than 1 for paclitaxel
      over cephalomannine for both solvents. Selectivity coefficient increases to 1.7
      with extraction in n-hexane, but the partition coefficient decreases to 1.9.
      Altering the pH of the aqueous phase results in an increase in both recovery and
      selectivity using n-hexane but does not change the results for other solvents
      significantly. The addition of extractants trioctylamine (TOA) or
      tributylphosphate (TBP) to n-hexane gives significantly higher partition
      coefficients for paclitaxel (8.6 and 23.7, respectively) but no selectivity.
      Interestingly, when 20% hexafluorobenzene (HFB) is added to n-hexane, the
      partition coefficient remains approximately constant, but the selectivity
      coefficient for paclitaxel over cephalomannine improves to 4.5. This significant
      increase in selectivity early in the purification process has the potential to
      simplify downstream processing steps and significantly reduce overall
      purification costs.

PMID- 22581675
TI  - [Actual care and funding situation with regard to mother-child units for psychic
      disorders associated with pregnancy in Germany].
AB  - CONCERN: The current care and financial situation of mother-child units for
      psychic disorders associated with pregnancies in Germany should be documented in
      preparation for the development of the new reimbursement system for psychiatry
      and psychosomatics. METHOD: In accordance with the last survey of 2005, a brief
      questionnaire was developed and a nationwide poll was conducted. RESULTS: The
      survey revealed severe (10 fold) service deficits for severely and gravely
      mentally ill mothers, who require an inpatient treatment with specific
      professional competence. Compared with the last poll, these service deficits have
      increased. This is due to continued insufficient funding and unresolved financing
      in the new reimbursement system. With the establishment of an additional code for
      mother-child treatment the precondition for ensuring the funding of this
      important care form in the new reimbursement system was created. CONCLUSION: It
      is to be hoped that the decision-makers of health policy will finally face up to
      their social responsibility and ensure adequate funding of the additional
      diagnostic and therapeutic expenditure of mother-child treatment. The health care
      providers have an obligation to implement a transparent record of services of the
      additional expenditure and to augment the national evaluation approaches to
      inpatient mother-child treatments.

PMID- 22581676
TI  - Osmotic stress adaptations in rhizobacteria.
AB  - Rhizobacteria have been reported to be beneficial to the plants in many different
      ways. Increasing salinity in the coastal agricultural zones has been shown to be
      a threat to the plant and microbial life in the area. Exposure of microorganisms
      to high-osmolality environments triggers rapid fluxes of cell water along the
      osmotic gradient out of the cell, thus causing a reduction in turgor and
      dehydration of the cytoplasm. The microorganisms have developed various
      adaptations to counteract the outflow of water. The first response to osmotic up
      shifts and the resulting efflux of cellular water is uptake of K+ and cells start
      to accumulate compatible solutes. Yet another mechanism is by altering the cell
      envelope composition resulting in changes in proteins, periplasmic glucans, and
      capsular, exo and lipopolysaccharides. Bacteria also initiate a program of gene
      expression in response to osmotic stress by high NaCl concentrations, which are
      manifested as a set of proteins produced in increased amounts in response to the
      stress. Genomics, transcriptomics and proteomics approaches have revealed the key
      components in molecular basis of bacteria salt adaptation. Understanding the
      mechanisms of osmo-adaptation in rhizobacteria would also be relevant from an
      ecological and an applicative point of view.

PMID- 22581677
TI  - Intelligence, birth order, and family size.
AB  - The analysis of the National Child Development Study in the United Kingdom (n =
      17,419) replicates some earlier findings and shows that genuine within-family
      data are not necessary to make the apparent birth-order effect on intelligence
      disappear. Birth order is not associated with intelligence in between-family data
      once the number of siblings is statistically controlled. The analyses support the
      admixture hypothesis, which avers that the apparent birth-order effect on
      intelligence is an artifact of family size, and cast doubt on the confluence and
      resource dilution models, both of which claim that birth order has a causal
      influence on children's cognitive development. The analyses suggest that birth
      order has no genuine causal effect on general intelligence.

PMID- 22581679
TI  - Some aspects of the host response to methacrylic acid containing beads in a mouse
      air pouch.
AB  - Exudate analysis indicated that both hydroxamated methacrylic acid-based (HX-MAA)
      and methacrylic acid-based (MAA) beads without hydroxamation, implanted in an air
      pouch with gelatin discs, elicited similar biological responses, with both
      resulting in high cell counts and chemokine (MCP3) levels, relative to control,
      poly(methyl methacrylate) (PMMA) beads. HX-MAA beads had been used elsewhere to
      restore homeostatic levels of extracellular matrix degrading enzymes, matrix
      metalloproteases, whereas the MAA beads (without hydroxamation) promoted
      angiogenesis in wound healing models. Furthermore, both beads appeared to
      activate exudate macrophages in the classical manner (high IL12/IL10 ratio) at
      day 4. Exudate macrophages, which were isolated by a magnetic bead protocol and
      analyzed by RT-PCR, showed a mixed response: elevated levels of an alternative
      marker (mannose receptor C type lectin) and a classical marker (IL6) were seen,
      in macrophages from the HX-MAA and MAA group compared to the PMMA group at day 4.
      A partial shift to an alternatively activated phenotype was seen by day 10.

PMID- 22581678
TI  - Locus-specific mutation databases for neurodegenerative brain diseases.
AB  - The Alzheimer disease and frontotemporal dementia (AD&FTLD) and Parkinson disease
      (PD) Mutation Databases make available curated information of sequence variations
      in genes causing Mendelian forms of the most common neurodegenerative brain
      disease AD, frontotemporal lobar degeneration (FTLD), and PD. They are
      established resources for clinical geneticists, neurologists, and researchers in
      need of comprehensive, referenced genetic, epidemiologic, clinical,
      neuropathological, and/or cell biological information of specific gene mutations
      in these diseases. In addition, the aggregate analysis of all information
      available in the databases provides unique opportunities to extract mutation
      characteristics and genotype-phenotype correlations, which would be otherwise
      unnoticed and unexplored. Such analyses revealed that 61.4% of mutations are
      private to one single family, while only 5.7% of mutations occur in 10 or more
      families. The five mutations with most frequent independent observations occur in
      21% of AD, 43% of FTLD, and 48% of PD families recorded in the Mutation
      Databases, respectively. Although these figures are inevitably biased by a
      publishing policy favoring novel mutations, they probably also reflect the
      occurrence of multiple rare and few relatively common mutations in the inherited
      forms of these diseases. Finally, with the exception of the PD genes PARK2 and
      PINK1, all other genes are associated with more than one clinical diagnosis or
      characteristics thereof.

PMID- 22581680
TI  - ALDH1 immunohistochemical expression and its significance in salivary adenoid
      cystic carcinoma.
AB  - BACKGROUND: Adenoid cystic carcinoma (ACC) cells with a high level of ALDH1, a
      known cancer stem cell (CSC) marker, had higher tumorigenic, invasive, and
      metastatic abilities. We examined the immunohistochemical expression of ALDH1 in
      ACC and its correlation with survival. METHODS: Archival paraffin blocks of ACC
      were analyzed. A tissue microarray was constructed and immunohistochemical
      expression of ALDH1 was analyzed using anti-ALDH1 monoclonal antibody.
      Correlations between ALDH1 expression and clinical and histological parameters
      were assessed by chi-square tests. Survival was assessed by the Kaplan-Meier
      method and log-rank test. RESULTS: Most of the tumors (63%) showed stromal
      staining only, 11% of the tumors showed both epithelial and stromal expression,
      and 26% of the tumors did not show either epithelial or stromal staining.
      Statistical analyses did not show any correlation between the pattern of ALDH1
      expression and tumor histology, tumor size, or perineural invasion. There were no
      significant differences in survival among the 3 patterns of ALDH1 expression.
      CONCLUSION: Other factors, besides CSCs, may play important roles in
      tumorigenesis, cell differentiation, and tumor progression in these tumors.

PMID- 22581681
TI  - On the electrochemistry and spectroelectrochemistry of small model star-shaped
      compounds: 1,3,5-triaryl-1-methoxybenzenes and 2,4,6-triaryl-1,3,5
      trimethoxybenzenes.
AB  - Model structures of 1,3,5-triarylbenzenes with a substituted benzene core linked
      to thienyl or 3,4-ethylenedioxythienyl (EDOT) terminal groups are studied by
      electrochemical and in situ ESR/UV/Vis/NIR spectroelectrochemical techniques.
      Oxidative polymerization of the monomers results in C-C coupling of the thiophene
      moieties in the 5-position, forming dimeric structures with bithiophene linkers
      as the first step. Both the doubly charged protonated dimer and the new dimer
      formed after proton release are studied in detail for 2,4,6-tris[2-(3,4
      ethylenedioxythienyl)]-1-methoxybenzene. Quite high stability of the doubly
      charged sigma dimer formed on oxidation with unusual redox behavior at the
      electrode is observed. Density functional calculations of the molecular structure
      as well as spectroscopic and electronic properties of charged states in 1,3,5
      triarylbenzene derivatives in the monomeric, dimeric, and oligomeric form are
      presented. The complex spectroelectrochemical response of a thin solid film
      formed on the electrode surface upon potentiodynamic polymerization indicates the
      existence of different charge states of oligomeric structures within the solid
      matrix.

PMID- 22581683
TI  - Stroke volume does not plateau in female endurance athletes.
AB  - It has been a long-lasting debate whether the heart's stroke volume (SV)
      increases at high aerobic intensities or plateau. Further, sex and level of
      aerobic power are shown to influence the response. The purpose of this study was
      to investigate the SV at increasing intensities in elite female athletes and
      moderately trained females. 13 elite athletes and 11 moderately trained controls
      with maximal oxygen consumption (VO(2max)) of 67.1 +/- 6.1 and 49.5 +/- 2.3 mL ?
      min (- 1) ? kg (- 1), respectively, were recruited. SV was measured at rest, and
      running on a treadmill at 40%, 60%, 80% and 100% of VO(2max) using the single
      breath acetylene uptake (SB) technique. Both groups showed a significant (p<0.05)
      increase in SV from 40% of VO2max to VO(2max), with increases from 105.3 +/- 19.0
      to 129.1 +/- 16.3 mL? beat(-1) for the elite females and from 68.7 +/- 21.7 to
      82.7 +/- 14.0 mL ? beat (- 1) for the moderately trained. No differences were
      observed between groups in these increases, but the elite athletes displayed a
      larger (p<0.05) SV at all intensities. It is concluded that the SV increases at
      high aerobic intensities both in elite athlete females and moderately trained
      females.

PMID- 22581684
TI  - Response of salivary markers of autonomic activity to elite competition.
AB  - We investigated the response of salivary total protein (TP), alpha-amylase (sAA)
      and chromogranin A (CgA) to sporting competition and their relation with positive
      and negative affect. 11 professional swimmers were examined during the first day
      of a national contest and on a recreated event that matched time-of-the-day and
      day-of-the-week assessments 2 weeks later. Total protein was determined by the
      Bradford method and sAA and CgA by Western blotting upon awakening, 30 and 60 min
      post awakening, immediately before warming up for competition and 5, 20 and 60
      min after competition. Psychometric instruments included the Positive Affect and
      Negative Affect Schedule-X. The concentrations of TP, sAA and CgA differed from
      controls only prior to and 5 min after the event. We observed positive
      correlations between higher negative affect scores with higher levels of TP, sAA
      and CgA prior to the event on the competition day. All 3 markers showed a similar
      reactivity to sporting competition, which may be attributed to the mechanisms
      responsible for protein secretion into saliva when collection is performed with
      no exogenous stimulation. TP is an attractive marker in sports psychology since
      its determination is faster and cheaper than traditional kinetic or immune
      assays.

PMID- 22581685
TI  - Nanoporous walls on macroporous foam: rational design of electrodes to push areal
      pseudocapacitance.

PMID- 22581682
TI  - Halofuginone prevents estrogen-deficient osteoporosis in mice.
AB  - Osteoporosis is characterized by enhanced activity of osteoclasts relative to
      that of osteoblasts. Thus, the principal means of treating the most common form
      of osteoporosis, namely that attending menopause, is inhibition of osteoclast
      formation or function. We have demonstrated that the inflammatory cytokine, IL
      17, mediates estrogen-deficient osteoporosis, in mice, and that genetic blockade
      of its function prevents ovariectomy-induced bone loss. We herein report that the
      febrifugine derivative, halofuginone, a small molecule drug, reduces abundance of
      Th-17 cells in mice and prevents estrogen-deficient osteoporosis by diminishing
      bone resorption without impacting osteogenesis. In keeping with IL-17 mediating
      its osteoclastogenic effects by promoting RANK ligand expression by osteoblasts,
      halofuginone does not directly inhibit the bone resorptive cell. Thus,
      halofuginone, which is presently FDA-approved for treatment of scleroderma, is a
      candidate therapeutic for post-menopausal osteoporosis.

PMID- 22581686
TI  - Construction of a genetically engineered microorganism for phenanthrene
      biodegradation.
AB  - The bacterium Pseudomonas sp. CGMCC2953, isolated from oil-polluted soil, was
      used as a recipient for a biodegradative gene encoding catechol 2,3-dioxygenase
      (C23O), which was successfully cloned into the plasmid pK4 derived from pRK415
      with a broad host range. The apparent phenanthrene biodegradation parameters of
      the recombinant microorganism (Pseudomonas sp. CGMCC2953-pK) were determined and
      compared with those of the wild type. As the key enzyme of phenanthrene
      degradation, C23O, could be expressed constitutively in the recombinant strain,
      Pseudomonas sp. CGMCC2953-pK showed an increased ability to degrade phenanthrene.
      The excessive production of C23O in Pseudomonas sp. CGMCC2953-pK could serve as
      an effective approach to construct genetically engineered microorganisms for the
      bioremediation of environmental contaminations.

PMID- 22581687
TI  - Distribution and functional organization of glomeruli in the olfactory bulbs of
      zebrafish (Danio rerio).
AB  - Odor molecules are transduced by thousands of olfactory sensory neurons (OSNs)
      located in the nasal cavity. Each OSN expresses a single functional odorant
      receptor protein and projects an axon from the sensory epithelia to an olfactory
      bulb glomerulus, which is selectively innervated by only one or a few OSN types.
      We used whole-mount immunocytochemistry to study the neurochemistry and
      anatomical organization of glomeruli in the zebrafish olfactory system. By
      employing combinations of antibodies against G-protein alpha subunits, calcium
      binding proteins, and general neuronal markers, we selectively labeled various
      OSN types, their axonal projections to glomeruli, and the detailed anatomical
      distributions of individual glomeruli in different regions of the olfactory bulb.
      In this way we identified ~140 glomeruli in each olfactory bulb of mature
      zebrafish. A small subset (27) of these glomeruli was unambiguously identifiable
      in nearly all animals examined. These units were large and, located mainly in the
      medial olfactory bulbs. Most glomeruli, however, were comparatively small,
      anatomically indistinguishable, and located in coarsely circumscribed regions;
      almost all of these latter glomeruli were innervated by OSNs that were labeled
      with anti-G(alpha s/olf) and/or anti-calretinin antibodies. Collectively, our
      results provide a uniquely detailed description of a vertebrate olfactory system
      and highlight anatomically distinct parallel neural pathways that mediate early
      aspects of olfactory processing in the zebrafish.

PMID- 22581688
TI  - Astrocytes in the rat medial amygdala are responsive to adult androgens.
AB  - The posterodorsal medial amygdala (MePD) exhibits numerous sex differences
      including differences in volume and in the number and morphology of neurons and
      astroctyes. In adulthood, gonadal hormones, including both androgens and
      estrogens, have been shown to play a role in maintaining the masculine character
      of many of these sex differences, but whether adult gonadal hormones maintain the
      increased number and complexity of astrocytes in the male MePD was unknown. To
      answer this question we examined astrocytes in the MePD of male and female Long
      Evans rats that were gonadectomized as adults and treated for 30 days with either
      testosterone or a control treatment. At the end of treatment brains were
      collected and immunostained for glial fibrillary acidic protein. Stereological
      analysis revealed that adult androgen levels influenced the number and complexity
      of astrocytes in the MePD of both sexes, but the specific effects of androgens
      were different in males and females. However, sex differences in the number and
      complexity of adult astrocytes persisted even in the absence of gonadal hormones
      in adulthood, suggesting that androgens also act earlier in life to determine
      these adult sex differences. Using immunofluorescence and confocal microscopy, we
      found robust androgen receptor immunostaining in a subpopulation of MePD
      astrocytes, suggesting that testosterone may act directly on MePD astrocytes to
      influence their structure and function.

PMID- 22581691
TI  - Design of injectable organic-inorganic hybrid for bone tissue repair.
AB  - Injectable bone substitutes are rapidly gained success in tissue engineering
      applications for their less invasive surgical aspect. Here, the design and the
      characterization of a novel degradable paste of PCL reinforced with nanocrystals
      of hydroxyapatite have been presented aiming to mimic natural tissue.
      Nanohydroxyapatite has been successfully synthesized via sol-gel technique.
      Dynamic and steady state viscoelastic properties of the solutions and paste were
      investigated to control the kinetic of phase transition. Correspondingly, the
      morphology and composition were characterized via TEM, EDAX, and thermal
      analysis. Injection test underlines the completely ability of the paste of being
      injected without altering its features. Preliminary biological study showed that
      the composite paste is not cytotoxic. The synergistic rheological and biological
      properties, combined with the positive effect of chemical synthesis method
      indicate that the composite paste is very suitable as local bone substitute in
      low-load areas.

PMID- 22581690
TI  - Toward a mtDNA locus-specific mutation database using the LOVD platform.
AB  - The Human Variome Project (HVP) is a global effort to collect and curate all
      human genetic variation affecting health. Mutations of mitochondrial DNA (mtDNA)
      are an important cause of neurogenetic disease in humans; however, identification
      of the pathogenic mutations responsible can be problematic. In this article, we
      provide explanations as to why and suggest how such difficulties might be
      overcome. We put forward a case in support of a new Locus Specific Mutation
      Database (LSDB) implemented using the Leiden Open-source Variation Database
      (LOVD) system that will not only list primary mutations, but also present the
      evidence supporting their role in disease. Critically, we feel that this new
      database should have the capacity to store information on the observed phenotypes
      alongside the genetic variation, thereby facilitating our understanding of the
      complex and variable presentation of mtDNA disease. LOVD supports fast queries of
      both seen and hidden data and allows storage of sequence variants from high
      throughput sequence analysis. The LOVD platform will allow construction of a
      secure mtDNA database; one that can fully utilize currently available data, as
      well as that being generated by high-throughput sequencing, to link genotype with
      phenotype enhancing our understanding of mitochondrial disease, with a view to
      providing better prognostic information.

PMID- 22581692
TI  - Physical morbidity by surgical approach and tumor location in skull base surgery.
AB  - BACKGROUND: Skull base tumors are associated with physical symptoms that vary
      depending on location and surgical approach. METHODS: Skull base surgery patients
      (n = 138) were retrospectively reviewed and physical symptoms were quantified.
      Patients were divided into 4 groups by surgical approach (open, endoscopic) and
      tumor location (anterior, central). Multivariate analyses determined odds for
      symptom development. RESULTS: Patients with anterior lesions presented with more
      nasal symptoms compared to those with central lesions (63% vs 6.8%; p < .001).
      Those with central lesions presented with more neurologic (41.1% vs 12.3%; p <
      .001) and endocrine symptoms (19.2% vs 0%; p < .001). Three of 4 groups
      experienced a reduction in neurologic and visual symptoms after surgery. One
      group (endoscopic/central) experienced a reduction in endocrine and an increase
      in nasal symptoms. Anterior tumors (p = .02) and endoscopic approaches (p = .002)
      predicted increased nasal morbidity. CONCLUSION: Physical morbidity from skull
      base tumors may vary based on tumor location and surgical approach.

PMID- 22581693
TI  - Percutaneous treatment of a post-TAVI ventricular septal defect: a successful
      combined procedure for an unusual complication.
AB  - In this report, we present the successful percutaneous ventricular septal defect
      (VSD) closure, just 1 week post-transcatheter aortic valve implantation (TAVI).
      Periprocedurally, after implantation of the 31-mm CoreValve in an intentionally
      "high" position, we balloon postdilated, with an excellent result. A week post
      TAVI, the patient started to deteriorate. Echocardiogram revealed a good working
      prosthesis; however, a perimembranous VSD was evident, causing significant shunt.
      We proceeded with interventional treatment of the defect, using an Amplatzer
      multifenestrated--"Cribriform"--septal occluder. Six months after the combined
      procedure, the patient showed marked improvement in symptoms and no shunt was
      observed.

PMID- 22581695
TI  - A review of mechanical and electromechanical properties of piezoelectric
      nanowires.
AB  - Piezoelectric nanowires are promising building blocks in nanoelectronic, sensing,
      actuation and nanogenerator systems. In spite of great progress in synthesis
      methods, quantitative mechanical and electromechanical characterization of these
      nanostructures is still limited. In this article, the state-of-the art in
      experimental and computational studies of mechanical and electromechanical
      properties of piezoelectric nanowires is reviewed with an emphasis on size
      effects. The review covers existing characterization and analysis methods and
      summarizes data reported in the literature. It also provides an assessment of
      research needs and opportunities. Throughout the discussion, the importance of
      coupling experimental and computational studies is highlighted. This is crucial
      for obtaining unambiguous size effects of nanowire properties, which truly
      reflect the effect of scaling rather than a particular synthesis route. We show
      that such a combined approach is critical to establish synthesis-structure
      property relations that will pave the way for optimal usage of piezoelectric
      nanowires.

PMID- 22581694
TI  - Alternation of extracellular matrix remodeling and apoptosis by activation of the
      aryl hydrocarbon receptor pathway in human periodontal ligament cells.
AB  - It is well known that the aryl hydrocarbon receptor (AhR) is involved in the
      toxicity of halogenated aromatic hydrocarbons (HAH) and polycyclic aromatic
      hydrocarbons (PAH). Recent experiments have shown the induction of impaired tooth
      and hard-tissue formation by AhR pathway activation, however, the effect on
      periodontal ligament (PDL) tissue remains unclear. Here, we investigated the
      effects of benzo(a)pyrene (BaP), a member of PAH, on the extracellular matrix
      (ECM) remodeling-related molecules, collagen type I (COL-I), matrix
      metalloproteinase-1 (MMP-1), alpha-smooth muscle actin (alpha-SMA) expression,
      and apoptosis in two different human periodontal ligament cells (HPDLCs). The
      transduction of AhR from the cytoplasm to the nucleus and the increase of AhR
      responsive genes; that is, cytochrome P450 1A1 (CYP1A1), cytochrome P450 1B1
      (CYP1B1), and aryl-hydrocarbon receptor repressor (AhRR), expression was induced
      by BaP exposure in both HPDLCs. BaP treatment significantly enhanced MMP-1 mRNA
      expression and MMP-1 protein production, while markedly suppressing COL-I and a
      SMA mRNA expression in both HPDLCs. Furthermore, these BaP-treated HPDLCs fell
      into apoptotic cell death as evidenced by induction in annexin V and caspase-3/7
      staining and reduction of total cell number and Bcl-2 mRNA expression. Thus, BaP
      exposure altered the expression of ECM-related molecules and induced apoptosis in
      HPDLCs through activation of the AhR pathway. Overactivity of the AhR pathway may
      induce an inappropriate turnover of PDL tissue via disordered ECM remodeling and
      apoptosis in PDL cells.

PMID- 22581696
TI  - Fe protein over-expression can enhance the nitrogenase activity of Azotobacter
      vinelandii.
AB  - The effects of over-expression of NifH (Fe protein) on nitrogenase activity in
      Azotobacter vinelandii UW cells were studied by expressing an extra nifH gene
      under the control of the inducible meta-toluic acid pathway promoter Pm. The
      total amount of protein in UW/pJB654-N reacting to anti-NifH antibody was 2-3
      fold of that in control UW when both the strains were grown to exponential phase
      in the presence of 4 MUM m-toluic acid. As a consequence UW/pJB654-N showed two
      fold higher acetylene reduction activity and released 70% higher amounts of
      ammonium into the growth medium than the control. Concomitant changes were
      observed also in the cellular levels of siderophores and iron superoxide
      dismutase (FeSOD). Thus, our results indicating that increased level of Fe
      protein in the cell can enhance nitrogen fixation activity of A. vinelandii may
      have biotechnological significance.

PMID- 22581697
TI  - Treatment results of chronic hepatitis C genotype 5 and 6 infections in Germany.
AB  - Chronic hepatitis C due to HCV genotype 5 and 6 infection is infrequently
      reported and patients are usually not included in trials. As boceprevir and
      telaprevir are not approved for these genotypes, pegylated interferon plus
      ribavirin will remain the treatment of choice for the coming years. Patients
      infected with HCV genotype 5 or 6 were identified by data base search from an
      ongoing observational cohort study in Germany. Of the total 23 893 patients, 39
      patients (0.2 %) carried a HCV genotype 5 and 39 patients a HCV genotype 6 (0.2
      %). Compared to other genotypes patients with genotype 5 were older and more
      often had a history of blood transfusion. Patients with genotype 6 were more
      often Asian and showed higher baseline alanine transaminase. Therapy with
      pegylated interferon alfa-2a and ribavirin was initiated in 24 patients with HCV
      genotype 5 and 27 patients with HCV genotype 6. After completion of 48 weeks of
      therapy an end of treatment response was achieved in 79 % and 81 % of treated
      patients, respectively. Sustained virological response was achieved in 58 % of
      patients with genotype 5 and in 59 % genotype 6 patients. HCV genotype 5 and 6
      infections are rare in Germany. Our findings suggest that most HCV genotype 6
      infections are seen in migrants from Asia, whereas HCV genotype 5 infections seem
      more due to spontaneous local infections. Sustained virological response seems to
      be better than for patients with genotype 1 or 4 with similar treatment duration.

PMID- 22581698
TI  - CO2 versus air insufflation for private practice routine colonoscopy: results of
      a randomized double blind trial.
AB  - BACKGROUND: Pain and bloating following colonoscopy are an underestimated
      problem, with 30 - 60 % of patients complaining of such symptoms. The use of CO2
      has been shown to significantly decrease pain after colonoscopy in academic
      hospital-based studies. The aim of the present study was to evaluate whether such
      an effect can also be seen during private practice routine colonoscopy. PATIENTS
      AND METHODS: In a prospective double-blind randomized trial, one experienced
      colonoscopist (> 12,000 examinations) used either air or CO2 insufflation for
      diagnostic or screening colonoscopy in consecutive patients presenting for
      diagnostic and screening colonoscopy in private practice. Outcome parameters were
      occurrence and duration of pain and bloating after colonoscopy based on a patient
      questionnaire. RESULTS: Of 180 randomized patients, 156 replies were analyzed
      (43.3 % male, mean age 61.7 +/- 9.7 years). There were no significant differences
      between the two groups with respect to age and sex distribution, indication,
      sedation, examination times and polypectomy rates. Both pain and abdominal
      bloating were significantly lower in the CO2 group. Abdominal pain and bloating
      in the CO2 vs. air group were absent in 84.4 vs. 64.6 % (p = 0.005) and 66.2 vs.
      32.9 % (p < 0.001). Moderate/strong symptoms were also significantly lower with
      CO2. CONCLUSIONS: The use of CO2 appears to be as effective in daily routine in
      private practice colonoscopy as reported in previous hospital-based studies.

PMID- 22581699
TI  - [CEUS as a tool to uncover an unusual cause of obstructive jaundice].
AB  - Aneurysms within the visceral arteries are rare. Among these, aneurysms of the
      splenic artery occur most frequently followed by aneurysms of the hepatic
      arteries. An early diagnosis is easily missed and almost all patients become
      symptomatic with an acute rupture associated with high mortality. Here we
      demonstrate the case of a 76-year-old patient who presented with acute upper
      abdominal pain accompanied by a single episode of vomiting and pyrexia of 39 
      degrees C. Laboratory results presented the picture of an obstructive jaundice
      without evidence for accompanying pancreatitis. Inflammatory markers were within
      normal limits at onset, but increased dramatically within the next few days. An
      acute calculous cholecystitis was diagnosed on abdominal ultrasound whereas
      gastroscopy revealed no relevant changes. Computed tomography was suspicious for
      pancreatitis of the head with obstruction of the bile duct. Choledocholithiasis
      was ruled out by ERCP, but symptoms persisted despite papillotomy. Due to raising
      inflammatory markers and an ongoing impairment of the patients condition, an
      abdominal CT scan was repeated which revealed the suspicion of a ruptured
      aneurysm of the common hepatic artery. At the time of transferral we were able to
      confirm the diagnosis by contrast-enhanced ultrasound and angiography. The
      patient was immediately forwarded to surgery due to lack of satisfactory
      endovascular procedures. In summary, the patient suffered from a ruptured spurial
      aneurysm of the right gastric artery thereby obstructing the common bile duct.
      Beside CT scans and angiography, this case documents a pivotal role for contrast
      enhanced ultrasound in the work-up of visceral artery aneurysms.

PMID- 22581700
TI  - [EHEC-associated colon stenosis after ulcerous-chronic haemorrhagic colitis and
      consecutive resulting ileus].
AB  - We report on the case of a segmentally emphasised, ulcerous chronic haemorrhagic
      colitis with the development of granulation tissue und scarred fibrosis with
      consecutive resulting stenosis of the colon. A 49-year-old male patient was
      infected with enterohaemorrhagic Escherichia coli bacteria during the EHEC
      epidemic in northern Germany in early summer 2011. In the course of the infection
      the patient suffered from haemolytic uraemic syndrome (HUS) with acute renal
      failure and neurological symptoms. Haemodialysis and plasmapheresis had become
      mandatory. A simultaneous ileus was estimated to be of paralytic origin. One
      month after treatment of the acute phase of the infection a CT scan of the
      abdomen was performed and discovered a symptomatic stenosis of the proximal colon
      transversum. This obstruction needed to be treated by performing a right
      hemicolectomy with an ileo-transverso anastomosis. After surgery the patient
      recovered continuously. The histopathological examination verified an ulcerous
      chronic haemorrhagic colitis on the background of an EHEC infection.

PMID- 22581701
TI  - Imaging of gastrointestinal stromal tumours with modern ultrasound techniques - a
      pictorial essay.
AB  - Gastrointestinal stromal tumours (GIST) are rare tumours of the gastrointestinal
      tract. Dealing with these tumours requires a profound knowledge of the nature of
      the lesions and their malignant potentials. Modern ultrasound techniques provide
      the necessary tools to give the clinician the information he needs to diagnose
      and treat the patient. This article reviews the actual pathophysiological
      knowledge of GIST and provides a broad spectrum of ultrasound findings to
      introduce the reader into modern ultrasound investigation methods of
      subepithelial tumours. It covers the transcutaneous as well as the endoscopic
      ultrasound approach. Different conditions of GIST like the low risk or high risk
      form as well as the metastatic form will be discussed in diagnosis and treatment
      with plenty of examples. Special attention is paid to contrast-enhanced
      ultrasound techniques and elastography from the transcutaneous as well as the
      endoscopic route. Other diagnostic methods like CT, MRI and PET CT are
      additionally reviewed and their role in clinical practice is compared with that
      of ultrasound. The aim of the article is to introduce the reader into the new
      ultrasound techniques and special diagnostic behaviour of GIST and outline
      clinical pathways to deal correctly with different stages of the disease.

PMID- 22581702
TI  - Aspects in the interdisciplinary decision-making for surgical intervention in
      ulcerative colitis and its complications.
AB  - Ulcerative colitis (UC) is a chronic inflammation of the large bowel,
      predominantly affecting young adults of 20 to 30 years of age. Even though the
      majority of patients with limited and extensive UC can be managed medically, 20
      to 30 % will require surgical intervention at some point in their life to gain
      control of the inflammatory process. The most common reason for urgent and
      emergency surgery is a lack of response to maximal medical inpatient therapy
      after five to ten days. Other indications include hemorrhage, free perforation,
      sepsis, and toxic megacolon. Procedure of choice for the majority of surgeons is
      open or laparoscopic subtotal colectomy and end ileostomy, with or without
      exteriorization of the rectal stump. The laparoscopic approach requires more
      time, but allows for faster return of bowel function and discharge from the
      hospital. Creation of a definite restoration in form of a J pouch should be
      delayed for at least three months. Indications for elective surgical intervention
      include cancer, dysplasia associated lesion or mass, and stricture. Preferably,
      the J pouch and Brooke ileostomy are performed in two stages, with a takedown of
      the ileostomy several months later. A single-stage operation is associated with
      increased anastomotic dehiscence, sepsis, and long-term pouch failure. The
      laparoscopic creation of a J pouch is largely dependent on the surgeon's
      experience, but results in a number of advantages, including faster return of
      bowel function, tolerance of diet, and discharge. Regardless of emergency,
      urgent, or elective surgical intervention, early involvement of a team of
      gastroenterologist, surgeon, nutritionist, and stoma nurse is essential in the
      management of severe UC to maximize a satisfactory patient outcome.

PMID- 22581703
TI  - Mismatch repair analysis of inherited MSH2 and/or MSH6 variation pairs found in
      cancer patients.
AB  - Mismatch repair (MMR) malfunction causes the accumulation of mismatches in the
      genome leading to genomic instability and cancer. The inactivation of an MMR gene
      (MSH2, MSH6, MLH1, or PMS2) with an inherited mutation causes Lynch syndrome
      (LS), a dominant susceptibility to cancer. MMR gene variants of uncertain
      significance (VUS) may be pathogenic mutations, which cause LS, may result in
      moderately increased cancer risks, or may be harmless polymorphisms. Our study
      suggests that an inherited MMR VUS individually assessed as proficient may,
      however, in a pair with another MMR VUS found in the same colorectal cancer (CRC)
      patient have a concomitant contribution to the MMR deficiency. Here, eight pairs
      of MMR gene variants found in cancer patients were functionally analyzed in an in
      vitro MMR assay. Although the other pairs do not suggest a compound deficiency,
      the MSH2 VUS pair c.380A>G/c.982G>C (p.Asn127Ser/p.Ala328Pro), which nearly
      halves the repair capability of the wild-type MSH2 protein, is presumed to
      increase the cancer risk considerably. Moreover, two MSH6 variants, c.1304T>C
      (p.Leu435Pro) and c.1754T>C (p.Leu585Pro), were shown to be MMR deficient. The
      role of one of the most frequently reported MMR gene VUS, MSH2 c.380A>G
      (p.Asn127Ser), is especially interesting because its concomitant defect with
      another variant could finally explain its recurrent occurrence in CRC patients.

PMID- 22581704
TI  - Physicochemical properties of epidermal growth factor receptor inhibitors and
      development of a nanoliposomal formulation of gefitinib.
AB  - Inhibitors of epidermal growth factor (EGF) receptor (EGFR) tyrosine kinases show
      efficacy in cancers that are highly addicted to nonmutated EGF signaling, but off
      target effects limit therapy. Carrier-based formulations could reduce drug
      deposition in normal tissues, enhance tumor deposition, and reduce free drug
      concentrations, thereby reducing the side effects. Therefore, the feasibility of
      developing nanoliposomal formulations of EGFR inhibitors was investigated.
      Gefitinib and erlotinib fluorescence was characterized as a tool for formulation
      development. Peak excitation was 345 nm and peak emission was 385-465 nm,
      depending upon the environment polarity. Emission was negligible in water but
      intense in nonpolar solvents, membranes, or bound to serum proteins. Cellular
      uptake and distribution could also be imaged by fluorescence in drug-resistant
      tumor spheroids. Gefitinib fluorescence characteristics enabled facile
      optimization of formulations. Although 4-6 mol % gefitinib could be incorporated
      in the liposome bilayer, 40-60 mol % could be encapsulated in stable, remote
      loaded liposomes consisting of distearoylphosphatidylcholine-polyethylene glycol
      distereoylphosphatidylethanolamine-cholesterol (9:1:5 mol:mol:mol). Drug leakage
      in serum, monitored by fluorescence, was minimal over 24 h at 37 degrees C. The
      results provide both promising lead formulations as well as novel tools for
      evaluating new formulations of structurally similar receptor tyrosine kinase
      inhibitors and their cellular uptake and tissue biodistribution.

PMID- 22581705
TI  - Layer-by-layer assembly of antibacterial coating on interbonded 3D fibrous
      scaffolds and its cytocompatibility assessment.
AB  - Bonded fibrous matrices have shown great potential in tissue engineering because
      of their unique 3D structures and pore characteristics. For some applications,
      bacterial infections must be taken into account, and antibacterial function is
      highly desired. In this study, an antibacterial polymer, polyhexamethylene
      biguanide (PHMB), was applied onto the fiber surface of a bonded poly(epsilon
      caprolactone) (PCL) fibrous matrix with the objective to achieve both strong
      antibacterial effect and good cell compatibility. The coatings were prepared by
      using an electrostatic layer-by-layer (LbL) assembly technique, which allowed the
      control of PHMB loading and coating uniformity on the fiber surface. The PHMB
      coating provided antibacterial activities, but had no toxicity on mammalian
      cells. This bonded PCL fibrous matrix with electrostatically self-assembled PHMB
      may provide a new antiinfective tissue scaffold for various biomedical
      applications.

PMID- 22581706
TI  - Stem cells: a view from the roots.
AB  - In both plants and animals, regeneration requires the activation of stem cells.
      This is possibly related to the origin and requirements of multicellularity.
      Although long diverged from a common ancestry, plant and animal models such as
      Arabidopsis, Drosophila and mouse share considerable similarities in stem cell
      regulation. This includes stem cell niche organisation, epigenetic modification
      of DNA and histones, and the role of small RNA machinery in differentiation and
      pluripotency states. Dysregulation of any of these can lead to premature ageing,
      patterning and specification defects, as well as cancers. Moreover, emerging
      basal animal and plant systems are beginning to provide important clues
      concerning the diversity and evolutionary history of stem cell regulatory
      mechanisms in eukaryotes. This review provides a comparative framework,
      highlighting both the commonalities and differences among groups, which should
      promote the intelligent design of artificial stem cell systems, and thereby fuel
      the field of biomaterials science.

PMID- 22581707
TI  - Ipsilateral neck nodal status as predictor of contralateral nodal metastasis in
      carcinoma of tongue crossing the midline.
AB  - BACKGROUND: In squamous cell carcinoma of the tongue, when lesions reach or cross
      the midline, there is a higher risk of contralateral nodal metastasis.
      Identifying factors that are associated with higher risk of nodal metastasis may
      help in optimizing the treatment. METHODS: A retrospective analysis was conducted
      of all patients with squamous cell carcinoma of the tongue who had undergone
      bilateral neck dissection at Tata Memorial Hospital between January 2007 and June
      2010 for a lesion crossing or reaching the midline. RESULTS: Contralateral nodal
      metastases were present in 71 of 243 patients (29%) who underwent bilateral neck
      dissection. Of these 71 patients, 69 patients (97%) had ipsilateral nodal
      metastasis. CONCLUSION: In carcinoma of the tongue, where lesions reach or cross
      the midline, the chance of contralateral nodal metastases without ipsilateral
      nodal metastasis is extremely rare. Frozen section of ipsilateral neck dissection
      can be a pointer for addressing the contralateral neck.

PMID- 22581708
TI  - Longitudinal compression of the platinum-chromium everolimus-eluting stent during
      coronary implantation: predisposing mechanical properties, incidence, and
      predictors in a large patient cohort.
AB  - OBJECTIVES: To assess the longitudinal compression behavior of platinum-chromium
      everolimus-eluting stents, evaluate frequency of inadvertent longitudinal
      compression during percutaneous intervention, and define patient- and lesion
      related predictors of this complication. BACKGROUND: Platinum-chromium stents of
      Element family have unique design features to improve flexibility that may,
      however, impair longitudinal stability. Incidence of longitudinal stent
      compression during implantation and predictors for this complication are not well
      understood. METHODS: Five contemporary stent platforms were longitudinally
      compressed in a bench test experiment, and spring constant, yield force, and
      ultimate strength were calculated from force-strain curves. We also evaluated all
      coronary cases treated with an Element stent from January 1, 2010, to October 31,
      2011, for documented longitudinal compression. We compared baseline
      characteristics and periprocedural data between patients with and without
      longitudinal stent compression and assessed predictors for this event by multiple
      logistic regression models. RESULTS: Yield force and ultimate strength were
      significantly lower for the Element compared with all other tested stents. In 20
      patients (1.4%) and 20 lesions (0.7%) from 1,392 cases with 2,839 atherosclerotic
      lesions longitudinal stent compression was reported. Ostial segments, number of
      stents, and the presence of a bifurcation were significant predictors (adjusted
      odds ratios [95% confidence intervals]: 8.33 [3.30-21.28], 1.57 [1.01-2.45], 3.57
      [1.36-9.35], respectively). CONCLUSION: The Element stent exhibits the lowest
      overall longitudinal strength compared with four contemporary platforms.
      Longitudinal compression of the Element stent is a rare complication and occurs
      more frequently in ostial or bifurcation lesions and with multiple stents.

PMID- 22581709
TI  - An insertion in loop L7 of human eosinophil-derived neurotoxin is crucial for its
      antiviral activity.
AB  - The human eosinophil granule ribonuclease, eosinophil-derived neurotoxin (EDN)
      has been shown to have antiviral activity against respiratory syncytial virus-B
      (RSV-B). Other closely related and more active RNases such as RNase A, onconase,
      and RNase k6 do not have any antiviral activity. A remarkable unique feature of
      EDN is a nine-residue insertion in its carboxy-terminal loop, L7 which is not
      present in RNase A, and differs in sequence from the corresponding loop in
      another eosinophil RNase, eosinophil cationic protein (ECP). ECP has a much lower
      antiviral activity as compared to EDN. The current study probed the role of loop
      L7 of EDN in its antiviral activity. Three residues in loop L7, Arg117, Pro120,
      and Gln122, which diverge between EDN, ECP, and RNase A, were mutated to alanine
      alone and in combination to generate single, double, and triple mutants. These
      mutants, despite having RNase activity had decreased antiviral activity towards
      RSV suggesting the involvement of loop L7 in the interaction of EDN with RSV. It
      appears that the mutations in loop L7 disrupt the interaction of protein with the
      viral capsid, thereby inhibiting its entry into the virions. The study
      demonstrates that besides the RNase activity, loop L7 is another important
      determinant for the antiviral activity of EDN.

PMID- 22581710
TI  - Hybrid materials and polymer electrolytes for electrochromic device applications.
AB  - Electrochromic (EC) materials and polymer electrolytes are the most imperative
      and active components in an electrochromic device (ECD). EC materials are able to
      reversibly change their light absorption properties in a certain wavelength range
      via redox reactions stimulated by low direct current (dc) potentials of the order
      of a fraction of volts to a few volts. The redox switching may result in a change
      in color of the EC materials owing to the generation of new or changes in
      absorption band in visible region, infrared or even microwave region. In ECDs the
      electrochromic layers need to be incorporated with supportive components such as
      electrical contacts and ion conducting electrolytes. The electrolytes play an
      indispensable role as the prime ionic conduction medium between the electrodes of
      the EC materials. The expected applications of the electrochromism in numerous
      fields such as reflective-type display and smart windows/mirrors make these
      materials of prime importance. In this article we have reviewed several examples
      from our research work as well as from other researchers' work, describing the
      recent advancements on the materials that exhibit visible electrochromism and
      polymer electrolytes for electrochromic devices. The first part of the review is
      centered on nanostructured inorganic and conjugated polymer-based organic
      inorganic hybrid EC materials. The emphasis has been to correlate the structures,
      morphologies and interfacial interactions of the EC materials to their electronic
      and ionic properties that influence the EC properties with unique advantages. The
      second part illustrates the perspectives of polymer electrolytes in
      electrochromic applications with emphasis on poly (ethylene oxide) (PEO), poly
      (methyl methacrylate) (PMMA) and polyvinylidene difluoride (PVDF) based polymer
      electrolytes. The requirements and approaches to optimize the formulation of
      electrolytes for feasible electrochromic devices have been delineated.

PMID- 22581711
TI  - Isolation and screening of strains producing high amounts of rutin degrading
      enzymes from Fagopyrum tataricum seeds.
AB  - The rutin degrading enzyme (RDE) was isolated and purified from tartary buckwheat
      seeds. The RDE was purified about 11.34-fold and its final yield was 3.5%, which
      was very low, due to our purification strategy of giving priority to purity over
      yield. The RDE molecular weight was estimated to be about 60 kDa. When rutin was
      used as substrate, an optimal enzyme activity was seen at around pH 5.0 and 40 
      degrees C. Strains isolation strategy characterized by the use of rutin as sole
      carbon source in enrichment cultures was used to isolate RDE-producing strains.
      Then the active strains were identified by morphology characterization and 18s
      rDNA-ITS (Internal Transcribed Spacer) gene sequencing. Three isolates coded as
      B3, W2, Y2 were successfully isolated from fusty Fagopyrum tataricum flour
      cultures. Strain B3 possessed the highest unit activity among these three
      strains, and its total activity reached up to 171.0 Unit. The active isolate (B3)
      could be assigned to Penicillium farinosum. When the Penicillium farinosum
      strains were added to tartary buckwheat flour cultures at pH 5.0, 30  degrees C
      after 5 days fermentation, the quercetin production raised up to 1.78 mg/l,
      almost 5.1 times higher than the fermentation without the above active strains.
      Hence, a new approach was available to utilize microorganism-aided fermentation
      for effective quercetin extraction from Fagopyrum tataricum seeds.

PMID- 22581712
TI  - The role of breast MRI in planning the surgical treatment of breast cancer.
AB  - PURPOSE: To determine the frequency by which breast magnetic resonance imaging
      (MRI) provides information that influences the surgical management of patients
      with breast cancer. MATERIALS AND METHODS: From August 2006 to December 2008,
      contrast-enhanced bilateral breast MRI was performed on 68 patients, all of whom
      exhibited highly suspicious imaging findings (BI-RADS category 4 or 5). Patients
      were grouped according to their histopathological diagnosis and type of breast
      parenchyma. All of the enrolled patients were believed to be candidates for
      breast conservation on the basis of physical examination, mammography, and
      ultrasonography. The patients were reevaluated with the MRI examination as to
      whether they were still candidates for breast conservation therapy. RESULTS: The
      MRI findings changed the previous management plans in 19.1% of the 68 patients.
      With respect to the surgical approach, no statistically significant difference
      was observed between the histopathology groups (P = 0.403). In terms of the
      breast parenchymal pattern, however, surgical planning was changed in 53.8% of
      the patients who exhibited a dense pattern, which was significantly different
      from the rates of the other groups (P = 0.006). The sensitivity, specificity,
      positive predictive value, and negative predictive value of the MRI for
      additional malignant lesion detection and identification were 85%, 98%, 92%, and
      96%, respectively. The agreement test revealed 86% agreement (very good) between
      the additional findings observed on the MRI and the histopathological results.
      CONCLUSION: If breast-conserving surgery is planned, an MRI should be performed
      in all women with suspected breast cancer, especially those exhibiting dense or
      heterogeneously dense breast parenchyma, for which the sensitivity of both
      ultrasonography and mammography is low.

PMID- 22581713
TI  - Optimal preservation of the shark retina for ultrastructural analysis: an
      assessment of chemical, microwave, and high-pressure freezing fixation
      techniques.
AB  - Recent advances in microwave chemical fixation (MCF) and/or high pressure
      freezing (HPF) combined with transmission electron microscopy have resulted in
      superior ultrastructural detail in a variety of tissue types. To date, selachian
      tissue has been fixed and processed using only standard chemical fixation (CF)
      methods, and the resulting ultrastructure has been less than ideal. In this
      study, we compared the ultrastructure of the fragile retinal tissue from the
      brown banded bamboo shark, Chiloscyllium punctatum, obtained using CF, MCF, and
      HPF methods. For all fixation protocols, ultrastructural preservation was
      improved by keeping the tissue in oxygenated Ringer solution until the time of
      fixation. Both MCF and HPF produced superior retinal ultrastructure compared to
      conventional CF. Although HPF occasionally resulted in very high quality
      ultrastructure, microwave fixation was almost comparable, quicker and far more
      consistent.

PMID- 22581714
TI  - Excipients differentially influence the conformational stability and
      pretransition dynamics of two IgG1 monoclonal antibodies.
AB  - Since immunoglobulins are conformationally dynamic molecules in solution, we
      studied the effect of stabilizing and destabilizing excipients on the
      conformational stability and dynamics of two IgG1 monoclonal antibodies (mAbs;
      mAb-A and mAb-B) using a variety of biophysical approaches. Even though the two
      mAbs are of the same IgG1 subtype, the unfolding patterns, aggregation behavior,
      and pretransition dynamics of these two antibodies were strikingly different in
      response to external perturbations such as pH, temperature, and presence of
      excipients. Sucrose and arginine were identified as stabilizers and
      destabilizers, respectively, on the basis of their influence on conformational
      stability for both the IgG1 mAbs. The two excipients, however, had distinct
      effective concentrations and different effects on the conformational stability
      and pretransition dynamics of the two mAbs as measured by a combination of
      differential scanning calorimetry, high-resolution ultrasonic spectroscopy, and
      red-edge excitation shift fluorescence studies. Stabilizing concentrations of
      sucrose were found to decrease the internal motions of mAb-B, whereas arginine
      marginally increased its adiabatic compressibility in the pretransition region.
      Both sucrose and arginine did not influence the pretransition dynamics of mAb-A.
      The potential reasons for such differences in excipient effects between two IgG1
      mAbs are discussed.

PMID- 22581715
TI  - Copolymer nanoparticles composed of sulfobetaine and poly(epsilon-caprolactone)
      as novel anticancer drug carriers.
AB  - Novel ABA type amphiphilic copolymers (PCL-APS-PCL) consisting of
      polycaprolactone (PCL) (A) as hydrophobic block and N,N'-bis (2-hydroxyethyl)
      methylamine ammonium propane sulfonate (APS) (B) as hydrophilic segment, self
      assembled into nanoparticles (NPs) with solvent evaporation method. The sizes and
      size distributions of NPs were characterized by dynamic light scattering. The
      morphology of NPs was observed by scanning electron microscopy (SEM). The
      critical micelle concentration (CMC) was determined by fluorescent probe. The
      drug loading content (DLC) and the drug release amount were characterized by UV
      visible spectrophotometer. The cytotoxicity of the NPs was measured by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenylte-trazoliumbromide (MTT) assay. It was found
      that the NPs were spherical in shape with sizes around 100 nm. The CMCs of the
      copolymers were quite low (*10(-4) mg/mL). The DLC decreased with lengthening of
      hydrophobic PCL block. In vitro drug release experiment demonstrated that the
      release rate of paclitaxel sped with the decrease of PCL length. MTT results
      showed that NPs were nontoxic to osteoblast and human epithelial carcinoma (hela)
      cells. After drug loading, NPs could restrain the growth of hela or even kill
      hela cells. Therefore, these preliminary studies suggest that the novel PCL-APS
      PCL NPs have a great potential application as anticancer drug-delivery carriers.

PMID- 22581716
TI  - Dermal metastases in squamous cell carcinomas of the head and neck.
AB  - BACKGROUND: Dermal metastases in squamous cell carcinomas of the head and neck
      are rare. The purpose of this study was to evaluate incidence, site, prognostic
      significance, and treatment modalities of dermal metastases of squamous cell
      carcinoma of the head and neck. METHODS: Medical records were retrospectively
      analyzed. Statistical analysis was performed using Fisher exact test, Cox
      regression, and Kaplan-Meier curves. RESULTS: Fifty-one patients with dermal
      metastases were evaluated. Dermal metastases were located in the neck, face,
      chest wall, and upper extremities. The median time from diagnosis of the primary
      tumor to the occurrence of dermal metastases was 16 months. Survival after
      manifestation of dermal metastases ranged from 1 to 65 weeks. Localization and
      treatment of dermal metastases did not significantly correlate with survival.
      CONCLUSION: Dermal metastases indicate the terminal phase of disease. No positive
      effect of certain therapy modalities could be validated. Therefore, invasive
      therapies should be abandoned in favor of best supportive care.

PMID- 22581718
TI  - Nanoribbon plasmonic gratings and their anomalous interaction with
      electromagnetic waves.

PMID- 22581717
TI  - Succinobucol-eluting stents increase neointimal thickening and peri-strut
      inflammation in a porcine coronary model.
AB  - OBJECTIVE: The aim of this study was to assess the efficacy of stent-based
      delivery of succinobucol alone and in combination with rapamycin in a porcine
      coronary model. BACKGROUND: Current drugs and polymers used to coat coronary
      stents remain suboptimal in terms of long term efficacy and safety. Succinobucol
      is a novel derivative of probucol with improved antioxidant and anti-inflammatory
      properties. METHODS: Polymer-free Yukon stents were coated with 1% succinobucol
      (SucES), 2% rapamycin (RES), or 1% succinobucol plus 2% rapamycin solutions
      (SucRES) and compared with a bare metal stent (BMS). RESULTS: The in vivo release
      profile of SucES indicated drug release up to 28 days (60% drug released at 7
      days); 41 stents (BMS, n = 11; SucES, n =10; RES, n = 10; SucRES, n = 10) were
      implanted in the coronary arteries of 17 pigs. After 28 days, mean neointimal
      thickness was 0.31 +/- 0.14 mm for BMS, 0.51 +/- 0.14 mm for SucES, 0.19 +/- 0.11
      mm for RES, and 0.36 +/- 0.17 mm for SucRES (P < 0.05 for SucES vs. BMS). SucES
      increased inflammation and fibrin deposition compared with BMS (P < 0.05),
      whereas RES reduced inflammation compared with BMS (P < 0.05). CONCLUSION: In
      this model, stent-based delivery of 1% succinobucol using a polymer-free stent
      platform increased neointimal formation and inflammation following coronary
      stenting.

PMID- 22581719
TI  - Branched-chain amino acid deficiency stabilizes insulin-induced vascular
      endothelial growth factor mRNA in hepatocellular carcinoma cells.
AB  - Abnormal sugar metabolism is closely related to chronic liver diseases, including
      hepatocellular carcinoma (HCC). We previously reported that fasting
      hyperinsulinemia is a poor prognostic factor for HCC patients. A recent large
      scale study has shown that long-term administration of branched chain amino acids
      (BCAA) reduces the risk of HCC development in obese cirrhotic patients who have
      been diagnosed with diabetes mellitus, although the mechanism by which it does so
      is unclear. In this study, we analyzed the expression of vascular endothelial
      growth factor (VEGF) in HepG2 cells under high-insulin culture conditions, and
      examined the effect of BCAA on VEGF expression. VEGF secretion was significantly
      increased by 200 nM of insulin under BCAA deficient conditions, but it was
      repressed by the addition of BCAA. BCAA activated the mTOR pathway and increase
      HIF-1alpha expression under high-insulin culture conditions, however quantitative
      PCR analysis showed that insulin-induced expression of VEGF mRNAs (VEGF121 and
      VEGF165) decreased 2 h after the addition of BCAA. The half-lives of both VEGF121
      and 165 mRNAs were shortened in the presence of BCAA compared to the absence of
      BCAA. Therefore it is thought that BCAA regulate VEGF expression mainly at the
      post-transcriptional level. We also examined which of the Valine, Leucine, and
      Isoleucine components of BCAA were essential for VEGF mRNA degradation. All three
      BCAA components were required for acceleration of insulin-induced VEGF mRNA
      degradation. These results suggest that administration of BCAA may downregulate
      VEGF expression in patients who have hyperinsulinemia and are in the process of
      developing HCC.

PMID- 22581720
TI  - Proliferative and apoptotic effects of gastric epithelial cells induced by
      coccoid Helicobacter pylori.
AB  - Helicobacter pylori exhibit morphology convertion in a spiral or coccoid form.
      This study aims to reveal the impact of coccoid H. pylori on the proliferation
      and apoptosis of gastric epithelial cells. The cagA and vacA genes of H. pylori
      were detected by semi-quantitative RT-PCR. Proliferation and apoptosis were
      analyzed by the CCK-8 colorimetric method and TUNEL assay, respectively. Egr-1
      mRNA and PCNA expression affected by the ERK1/2-specific inhibitor were detected
      by RT-PCR and immunochemistry. At low density of infection (MOI < 125:1), coccoid
      H. pylori exerted a stronger effect on proliferation and a weaker effect on
      apoptosis than did spiral form. The ERK1/2-specific inhibitor significantly
      blocked the increased expression in Egr-1 and PCNA induced by coccoid H. pylori.
      Expression of vacA and cagA in coccoid H. pylori decreased compared with the
      spiral form, whereas vacA decreased more than cagA. The difference of
      proliferation and apoptosis may be related to the unequal decreased expression of
      vacA and cagA in coccoid H. pylori. Activation of the ERK1/2-Egr-1-PCNA signal
      transduction pathway may play an important role in coccoid H. pylori-induced cell
      proliferation. Long latency of the coccoid form of H. pylori in gastric tissue
      may be associated with gastric cancer caused by H. pylori.

PMID- 22581721
TI  - Minimally invasive abdominal and thoracic surgery: principles and
      instrumentation.
AB  - Minimally invasive surgery, including laparoscopy, thoracoscopy, and endoscopic
      assisted procedures, is becoming more common in veterinary medicine. The basic
      principles of laparoscopy and thoracoscopy involve gaining access to a cavity
      through small incisions, creating a workspace, and maneuvering extracorporeally
      activated instruments within that workspace.

PMID- 22581722
TI  - Minimally invasive abdominal and thoracic surgery: techniques.
AB  - Laparoscopy, thoracoscopy, and other endoscopic-assisted procedures have many
      uses in veterinary medicine. Diagnosis and biopsy are currently the most common
      uses of minimally invasive techniques, but popularity for procedures such as
      ovariectomy, cancer staging, lung lobectomy, and pericardectomy is rising. This
      article touches on basic surgical procedures and describes some more advanced
      techniques.

PMID- 22581723
TI  - Hypercoagulability in dogs: treatment.
AB  - Hypercoagulability is a state in which the hemostatic balance shifts toward
      excessive platelet activation and fibrin deposition, leading to thrombosis.
      Although a definitive diagnosis is often difficult to make, identifying patients
      at risk for thromboembolism is critical. By identifying these patients and
      understanding mechanisms that contribute to hypercoagulability, clinicians can
      select protocols that aid in thrombus prevention. Several therapeutic options
      exist, including antiplatelet, anticoagulant, and fibrinolytic drugs.

PMID- 22581725
TI  - Respiratory distress due to retropharyngeal and neck swelling in a horse with
      mediastinal lymphosarcoma.
AB  - A 9-year-old, 1494-lb (679-kg) Quarter horse gelding in good body condition was
      admitted to the Veterinary Teaching Hospital, Western College of Veterinary
      Medicine (WCVM), University of Saskatchewan, for evaluation and treatment of
      acute respiratory distress. On a trail ride 26 days before presentation, the
      gelding had been exposed to a horse with clinical signs of an upper respiratory
      tract infection. The gelding performed well on the trail ride but, 4 days later,
      developed a mild swelling in the retropharyngeal area and a slight bilateral
      mucoid nasal discharge. The gelding was examined at the farm by its primary
      veterinarian, who made a presumptive diagnosis of strangles. Treatment was
      initiated using a combination of trimethoprim/sulfamethoxazole (30 mg/kg PO q12h
      for 1 week) and phenylbutazone (6 mg/kg PO q24h for the first 2 days, followed by
      3.5 mg/kg PO q24h for 5 more days). The gelding did not respond satisfactorily to
      antimicrobial and antiinflammatory therapy. During the following 2 weeks, the
      retropharyngeal swelling gradually became more pronounced and extended to the
      upper portion of the neck. Two days before presentation at WCVM, the gelding also
      developed a dry cough with difficult breathing, and the retropharyngeal and neck
      swelling extended to the pectoral region and ventral pectoral area extending to
      the cranial ventral abdomen. Because of progressing clinical signs and poor
      response to treatment, the horse was referred to WCVM for further evaluation.

PMID- 22581724
TI  - Nutritional management of osteoarthritis.
AB  - There is growing evidence of the role that nutrition can play in the management
      of veterinary patients with osteoarthritis. Current evidence supports nutritional
      management of body weight and dietary fortification with the long-chain omega-3
      fatty acids eicosapentaenoic acid and docosahexaenoic acid. Additional studies
      suggest that supplements and diet additives such as glucosamine, chondroitin
      sulfate, antioxidants, and green-lipped mussel may also have some benefit in
      managing osteoarthritis. Additional research evaluating pets with naturally
      occurring disease, using validated owner questionnaires and objective
      measurements, is needed.

PMID- 22581726
TI  - An application of ultraviolet spectroscopy to study interactions in proteins
      solutions at high concentrations.
AB  - Studies of protein-protein interactions (PPIs), especially in high-concentration
      solutions, have become increasingly important from a pharmaceutical perspective.
      Analytical methods used to study protein interactions, however, rely primarily on
      the detection of nonideality in relatively dilute (<50 mg/mL) solutions. We
      present here an application of variable-pathlength ultraviolet (UV)-visible
      absorption spectroscopy to examine and better understand such interactions over a
      wide concentration range (5-240 mg/mL) using several representative proteins. In
      this study, the change in UV absorption (or extinction coefficient) was monitored
      by determining delta absorbance (DeltaAbs), the difference between the measured
      absorbance and the corresponding theoretical absorbance (calculated from
      gravimetric dilution), over a wide range of protein concentrations. The DeltaAbs,
      corrected for light scattering, was found to increase with protein concentration
      for three model proteins (bovine serum albumin, lysozyme, and monoclonal
      antibody). Because PPIs influence solution viscosity, we studied the correlation
      between DeltaAbs measurements and viscosity as a function of protein
      concentration. The magnitude of DeltaAbs and solution viscosity followed similar
      trends with increasing protein concentration, albeit to different extents for
      different proteins. These data support the use of such DeltaAbs measurements as
      an alternative approach to monitor and evaluate interactions in protein solutions
      at high concentration.

PMID- 22581727
TI  - Phospholipid nanodisc engineering for drug delivery systems.
AB  - Biocompatible mesoscale nanoparticles (5-100 nm in diameter) are attractive tools
      for drug delivery. Among them are several types of liposomes and polymer micelles
      already in clinical trial or use. Generally, biocompatibility of such particles
      is achieved by coating them with polyethylene glycol (PEG). Without PEG coating,
      particles are quickly trapped in the reticuloendothelial system when
      intravenously administered. However, recent studies have revealed several
      potential problems with PEG coating, including antigenicity and restriction of
      cellular uptake. This has motivated the development of alternative drug and gene
      delivery vehicles, including chemically and genetically engineered high-density
      lipoprotein (HDL)-like nanodiscs or "bicelles". HDL is a naturally occurring
      mesoscale nanoparticle that normally ferries cholesterol around in the body. Its
      initial "nascent" form is thought to be a simple 10 nm disc of phospholipids in a
      bilayer, and can be easily synthesized in vitro by mixing recombinant apoA-I
      proteins with various phospholipids. In this review, the use of synthetic HDL
      like phospholipid nanodiscs as biocompatible drug carriers is summarized,
      focussing on manufacturing, size-control, drug loading and cell targeting.

PMID- 22581728
TI  - Investigating the role of substrate stiffness in the persistence of valvular
      interstitial cell activation.
AB  - During heart valve remodeling and in many disease states, valvular interstitial
      cells (VICs) shift to an activated myofibroblast phenotype characterized by
      enhanced synthetic and contractile activity. Pronounced alpha smooth muscle actin
      (alphaSMA)-positive stress fibers, the hallmark of activated myofibroblasts, are
      also observed in VICs cultured on stiff substrates especially in the presence of
      transforming growth factor-beta1 (TGF-beta1), however, the detailed relationship
      between stiffness and VIC phenotype has not been explored. The goal of this study
      was to characterize VIC activation as a function of substrate stiffness over a
      wide range of stiffness levels including that of diseased valves (stiff), normal
      valves (compliant), and hydrogels for heart valve tissue engineering (very soft).
      VICs obtained from porcine aortic valves were cultured on stiff tissue culture
      plastic to activate them, then, cultured on collagen-coated polyacrylamide
      substrates of predefined stiffness in a high-throughput culture system to assess
      the persistence of activation. Metrics extracted from regression analysis
      demonstrate that relative to a compliant substrate, stiff substrates result in
      higher cell numbers, more pronounced expression of alphaSMA-positive stress
      fibers, and larger spread area which is in qualitative agreement with previous
      studies. Our data also indicate that VICs require a much lower substrate
      stiffness level to "deactivate" them than previously thought. The high
      sensitivity of VICs to substrate stiffness demonstrates the importance of the
      mechanical properties of materials used for valve repair or for engineering valve
      tissue.

PMID- 22581729
TI  - Follow-up of parotid pleomorphic adenomas treated by extracapsular dissection.
AB  - BACKGROUND: This study was carried out to evaluate tumor recurrence following
      extracapsular dissection of pleomorphic adenomas of the parotid gland. METHODS:
      We conducted a retrospective evaluation and clinical follow-up of the patients
      who underwent extracapsular dissection of a pleomorphic adenoma as primary
      surgery in the otolaryngologic department of the Erlangen University Clinics
      during the period from 2000 to 2005. RESULTS: In all, 601 surgical interventions
      on benign parotid tumors were carried out from 2000 to 2005, 219 of which were
      primary operations for removal of a pleomorphic adenoma. In 76 patients (34.7%),
      extracapsular dissection of a primary pleomorphic adenoma was carried out. Tumor
      recurrence has not been observed in any of these patients to date after an
      average monitoring period of 7.38 years (range, 5.05-10.52 years). CONCLUSIONS:
      Extracapsular dissection is a conservative and safe surgical procedure for
      extirpation of pleomorphic adenomas that should be firmly established in the
      repertoire of parotid gland surgery.

PMID- 22581730
TI  - Multicompartmental particles for combined imaging and siRNA delivery.

PMID- 22581731
TI  - Plasma asymmetric dimethylarginine in patients with acute decompensation of
      chronic heart failure.

PMID- 22581732
TI  - Identifying the patient who FADES away prior to appropriate ICD intervention.

PMID- 22581733
TI  - Newly diagnosed glucose intolerance and prognosis after acute myocardial
      infarction: comparison of post-challenge versus fasting glucose concentrations.
AB  - BACKGROUND: Recent studies have demonstrated that newly diagnosed glucose
      intolerance is common among patients with acute myocardial infarction (AMI). The
      purpose of this study was to assess the long-term clinical cardiovascular
      outcomes in participants with AMI with abnormal fasting glucose compared with
      normal fasting glucose and an abnormal oral glucose tolerance test (OGTT)
      compared with a normal OGTT. METHODS: A prospective study was performed in 275
      consecutive patients with AMI, 85 of whom had pre-diagnosed diabetes mellitus
      (DM). Those without DM were divided into two groups based on the 75 g OGTT at the
      time of discharge. Abnormal glucose tolerance (AGT) was defined as 2 h glucose
      >=140 mg/dl; 78 patients had normal glucose tolerance (NGT) and 112 had AGT. The
      same patients were also reclassified into the normal fasting glucose group (NFG;
      n=168) or the impaired fasting glucose group (IFG; n=22). The association between
      the glucometabolic status and long-term major adverse cardiovascular event rates
      was evaluated. RESULTS: Kaplan-Meier survival curves showed that the AGT group
      had a worse prognosis than the NGT group and an equivalent prognosis to the DM
      group (p<0.0005). Cox proportional hazard model analysis showed that the HR of
      AGT to NGT for major adverse cardiovascular event rates was 2.65 (95% CI 1.37 to
      5.15, p=0.004) while the HR of DM to NGT was 3.27 (1.68 to 6.38, p=0.0005).
      However, Cox HR of IFG to NFG for major adverse cardiovascular event rates was
      1.83 (0.86 to 3.87), which was not significant. CONCLUSION: In patients with AMI,
      an abnormal OGTT is a better risk factor for future adverse cardiovascular events
      than impaired fasting blood glucose.

PMID- 22581734
TI  - Adenosine plasma level and A2A adenosine receptor expression: correlation with
      laboratory tests in patients with neurally mediated syncope.
AB  - OBJECTIVES: The purpose of this study was to investigate the hypothesis that
      responses to the ATP test and head-up tilt test (HUT) may be correlated with
      different purinergic profiles. DESIGN AND SETTING: The ATP and HUT identify
      distinct subsets of patients with neurally mediated syncope (NMS). Adenosine and
      its A(2A) receptors (A(2A)R) may be implicated in the pathophysiology of NMS in
      patients with positive HUT. Nothing is known about the purinergic profile of
      patients with positive ATP.   PATIENTS AND MEASURES:  This prospective study
      includes a consecutive series of patients with suspected NMS. All patients
      underwent both HUT and ATP. Before testing, samples were collected for
      measurement of baseline adenosine plasma level (APL) and expression. RESULTS: A
      total of 46 patients (25 men and 21 women) with a mean age of 57+/-18 years were
      enrolled. The HUT test was positive in 27 patients and the ATP test in 20. Both
      tests were positive in 9 and negative in 8. High APL was associated with high
      probability of positive HUT while low APL was associated with high probability of
      positive ATP. Expression of A(2A)R was lower in patients with positive ATP than
      in those with positive HUT. CONCLUSION: These findings indicate that patients
      with NMS present different purinergic profiles and that responses to HUT and ATP
      are correlated with these profiles.

PMID- 22581735
TI  - ASPIRE-2-PREVENT: a survey of lifestyle, risk factor management and
      cardioprotective medication in patients with coronary heart disease and people at
      high risk of developing cardiovascular disease in the UK.
AB  - OBJECTIVE: To determine in patients with coronary heart disease (CHD) and people
      at high risk of developing cardiovascular disease (CVD) whether the Joint British
      Societies' guidelines on CVD prevention (JBS2) are followed in everyday clinical
      practice. DESIGN: A cross-sectional survey was undertaken of medical records and
      patient interviews and examinations at least 6 months after the recruiting event
      or diagnosis using standardised instruments and a central laboratory for
      measurement of lipids and glucose. SETTINGS: The ASPIRE-2-PREVENT survey was
      undertaken in 19 randomly selected hospitals and 19 randomly selected general
      practices in 12 geographical regions in England, Northern Ireland, Wales and
      Scotland. PATIENTS: In hospitals, 1474 consecutive patients with CHD were
      identified and 676 (25.6% women) were interviewed. In general practice, 943
      people at high CVD risk were identified and 446 (46.5% women) were interviewed.
      RESULTS: The prevalence of risk factors in patients with CHD and high-risk
      individuals was, respectively: smoking 14.1%, 13.3%; obesity 38%, 50.2%; not
      reaching physical activity target 83.3%, 85.4%; blood pressure >=130/80 mm Hg
      (patients with CHD and self-reported diabetes) or >=140/85 mm Hg (high-risk
      individuals) 46.9%, 51.3%; total cholesterol >=4 mmol/l 52.6%, 78.7%; and
      diabetes 17.8%, 43.8%. CONCLUSIONS: The potential among patients with CHD and
      individuals at high risk of developing CVD in the UK to achieve the JBS2
      lifestyle and risk factor targets is considerable. CVD prevention needs a
      comprehensive multidisciplinary approach, addressing all aspects of lifestyle and
      risk factor management. The challenge is to engage and motivate cardiologists,
      physicians and other health professionals to routinely practice high quality
      preventive cardiology in a healthcare system which must invest in prevention.

PMID- 22581737
TI  - Heart transplantation: organisational aspects and current trends in
      immunosuppression--a view from Spain.

PMID- 22581736
TI  - Clinical prediction model for death prior to appropriate therapy in primary
      prevention implantable cardioverter defibrillator patients with ischaemic heart
      disease: the FADES risk score.
AB  - OBJECTIVES: To construct a risk score out of baseline variables to estimate the
      risk of death without prior implantable cardioverter defibrillator (ICD) in
      primary prevention ICD patients with ischaemic heart disease. DESIGN:
      Retrospective cohort study. SETTING: Tertiary care facility in The Netherlands.
      PATIENTS: All patients with ischaemic heart disease who received an ICD for
      primary prevention of sudden cardiac death at the Leiden University Medical
      Center, Leiden, The Netherlands in the period 1996-2009. MAIN OUTCOME MEASURE:
      All-cause mortality without prior appropriate ICD therapy (anti-tachycardia
      pacing or shock). RESULTS: 900 patients (87% men, mean age 64+/-10 years) were
      included in the analysis. During a median follow-up of 669 days (IQR 363-1322
      days), 150 patients (17%) died and 191 (21%) patients received appropriate device
      therapy. 114 (13%) patients died without prior appropriate therapy.
      Stratification of the risk for death without prior appropriate therapy resulted
      in risk categorisation of patients as low, intermediate or high risk. NYHA >=III,
      advanced age, diabetes mellitus, left ventricular ejection fraction <=25% and a
      history of smoking were significant independent predictors of death without
      appropriate ICD therapy. 5-year cumulative incidence for death without prior
      appropriate therapy ranged from 10% (95% CI 6% to 16%) in low-risk patients to
      41% (95% CI 33% to 51%) in high-risk patients. CONCLUSIONS: The risk of death
      without prior appropriate ICD therapy can be predicted in primary prevention ICD
      patients with ischaemic heart disease, which facilitates patient-tailored risk
      estimation.

PMID- 22581739
TI  - Balloons and atrial fibrillation.

PMID- 22581741
TI  - Left ventricular guidewire pacing for transcatheter aortic valve implantation.
AB  - Previous reports prove the safety and efficacy of cardiac pacing employing a
      guidewire in the left ventricle as unipolar pacing electrode. We describe the use
      of left ventricular guidewire pacing as an alternative to conventional
      transvenous temporary right ventricular pacing in the context of transcatheter
      aortic valve implantation.

PMID- 22581742
TI  - Biodegradation of keratinous waste by Chryseobacterium sp. RBT isolated from soil
      contaminated with poultry waste.
AB  - In the present study, a feather degrading bacterial strain was isolated from
      poultry waste disposal site, Kolhapur, India. The bacterium was identified as
      Chryseobacterium sp. RBT using 16S rRNA gene sequence analysis. Chryseobacterium
      sp. RBT showed rapid hydrolysis of native feathers within 30 h and produced the
      highest level of keratinase activity (98.3 U/ml). Keratin containing wastes viz.
      silk, human hair, wool and chicken feathers were tested for keratin degrading
      ability of the bacterium. Amongst the tested substrates, the Chryseobacterium sp.
      RBT showed more specificity towards chicken feathers (98.6% degradation) with
      maximum keratinase activity (98.3 U/ml) and solubilized protein concentration
      (3.84 mg/ml). Effect of various physico-chemical parameters (temperature, pH,
      carbon and nitrogen sources) on keratinase production was monitored. The maximum
      keratinase activity was observed at pH (8.6) and temperature (50  degrees C).
      Molasses (1.0% w/v) acted as an inducer and enhanced the keratinolytic activity
      by two fold, while starch worked as an inhibitor. The goat skin when treated with
      crude keratinase enzyme (2% v/v), showed complete dehairing within 12 h. Hence,
      Chryseobacterium sp. RBT shows potential as a candidate for treating the
      keratinous waste in an ecofriendly manner.

PMID- 22581743
TI  - Gastric emptying, intestinal absorption of electrolytes and exercise performance
      in electrolyte-supplemented horses.
AB  - Horses lose considerably more electrolytes through sweating during prolonged
      exercise than can be readily replaced through feeds. The present study tested an
      oral electrolyte supplement (ES) designed to replace sweat electrolyte losses. We
      measured gastric emptying of 3 litres of ES (using gamma imaging of (99)Tc
      sulfide colloid), the absorption of Na(+) and K(+) from the gastrointestinal
      tract using (24)Na(+) and (42)K(+), and the distribution of these ions in the
      body by measuring radioactivity within plasma and sweat during exercise. Three
      litres of ES emptied from the stomach as fast as water, with a half-time of 47
      min, and appeared in plasma by 10 min after administration (n = 4 horses). Peak
      values of plasma (24)Na(+) and (42)K(+) radioactivity occurred at 20-40 min, and
      a more rapid disappearance of K(+) radioactivity from plasma was indicative of
      movement of K(+) into cells (n = 3 horses). In a randomized crossover experiment
      (n = 4 horses), 1 h after administration of placebo (water), 1 or 3 litres of ES
      containing (24)Na(+), horses exercised on a treadmill at 30% of peak oxygen
      uptake until voluntary fatigue. The (24)Na(+) appeared in sweat at 10 min of
      exercise, and when horses received 3 litres of ES the duration to voluntary
      fatigue was increased in all horses by 33 +/- 10%. It is concluded that an oral
      ES designed to replace sweat ion losses was rapidly emptied from the
      gastrointestinal tract, rapidly absorbed in the upper intestinal tract and
      rapidly distributed within the body. The ES clearly served as a reservoir to
      replace sweat ion losses during exercise, and administration of ES prior to
      exercise resulted in increased duration of submaximal exercise.

PMID- 22581744
TI  - Individual differences in the cardiovascular responses to tonic muscle pain:
      parallel increases or decreases in muscle sympathetic nerve activity, blood
      pressure and heart rate.
AB  - We recently showed that acute muscle pain, induced by bolus intramuscular
      injection of hypertonic saline, causes a sustained increase in muscle sympathetic
      nerve activity (MSNA) and a modest increase in blood pressure and heart rate.
      However, it is not known whether long-lasting (tonic) pain, which more closely
      resembles chronic pain, causes a sustained increase in MSNA and blood pressure.
      We tested this hypothesis by recording MSNA in 12 healthy subjects. Tonic pain
      was induced for ~60 min by slow intramuscular infusion of hypertonic saline (7%)
      into the ipsilateral tibialis anterior muscle. Pain was sustained at a tolerable
      level (5/10 to 6/10 on a visual analog scale). Seven subjects showed progressive
      increases in mean MSNA amplitude during tonic pain, increasing to 154 +/- 17%
      (SEM) at 45 min and remaining essentially constant for the duration of the
      infusion. In these subjects, blood pressure and heart rate also increased.
      Conversely, for the other five subjects MSNA showed a progressive decline, with a
      peak fall of 67 +/- 11% at 40 min; blood pressure and heart rate also fell in
      these subjects. We conclude that tonic muscle pain has long-lasting effects on
      the sympathetic control of blood pressure, causing a sustained increase in some
      subjects yet a sustained decrease in others. This may have implications for
      individual differences in the cardiovascular consequences of chronic pain.

PMID- 22581745
TI  - Shortening and intracellular Ca2+ in ventricular myocytes and expression of genes
      encoding cardiac muscle proteins in early onset type 2 diabetic Goto-Kakizaki
      rats.
AB  - There has been a spectacular rise in the global prevalence of type 2 diabetes
      mellitus. Cardiovascular complications are the major cause of morbidity and
      mortality in diabetic patients. Contractile dysfunction, associated with
      disturbances in excitation-contraction coupling, has been widely demonstrated in
      the diabetic heart. The aim of this study was to investigate the pattern of
      cardiac muscle genes that are involved in the process of excitation-contraction
      coupling in the hearts of early onset (8-10 weeks of age) type 2 diabetic Goto
      Kakizaki (GK) rats. Gene expression was assessed in ventricular muscle with real
      time RT-PCR; shortening and intracellular Ca(2+) were measured in ventricular
      myocytes with video edge detection and fluorescence photometry, respectively. The
      general characteristics of the GK rats included elevated fasting and non-fasting
      blood glucose and blood glucose at 120 min following a glucose challenge.
      Expression of genes encoding cardiac muscle proteins (Myh6/7, Mybpc3, Myl1/3,
      Actc1, Tnni3, Tnn2, Tpm1/2/4 and Dbi) and intercellular proteins (Gja1/4/5/7, Dsp
      and Cav1/3) were unaltered in GK ventricle compared with control ventricle. The
      expression of genes encoding some membrane pumps and exchange proteins was
      unaltered (Atp1a1/2, Atp1b1 and Slc8a1), whilst others were either upregulated
      (Atp1a3, relative expression 2.61 +/- 0.69 versus 0.84 +/- 0.23) or downregulated
      (Slc9a1, 0.62 +/- 0.07 versus 1.08 +/- 0.08) in GK ventricle compared with
      control ventricle. The expression of genes encoding some calcium (Cacna1c/1g,
      Cacna2d1/2d2 and Cacnb1/b2), sodium (Scn5a) and potassium channels (Kcna3/5,
      Kcnj3/5/8/11/12, Kchip2, Kcnab1, Kcnb1, Kcnd1/2/3, Kcne1/4, Kcnq1, Kcng2, Kcnh2,
      Kcnk3 and Kcnn2) were unaltered, whilst others were either upregulated (Cacna1h,
      0.95 +/- 0.16 versus 0.47 +/- 0.09; Scn1b, 1.84 +/- 0.16 versus 1.11 +/- 0.11;
      and Hcn2, 1.55 +/- 0.15 versus 1.03 +/- 0.08) or downregulated (Hcn4, 0.16 +/-
      0.03 versus 0.37 +/- 0.08; Kcna2, 0.35 +/- 0.03 versus 0.80 +/- 0.11; Kcna4, 0.79
      +/- 0.25 versus 1.90 +/- 0.26; and Kcnj2, 0.52 +/- 0.07 versus 0.78 +/- 0.08) in
      GK ventricle compared with control ventricle. The amplitude of ventricular
      myocyte shortening and the intracellular Ca(2+) transient were unaltered;
      however, the time-to-peak shortening was prolonged and time-to-half decay of the
      Ca(2+) transient was shortened in GK myocytes compared with control myocytes. The
      results of this study demonstrate changes in expression of genes encoding various
      excitation-contraction coupling proteins that are associated with disturbances in
      myocyte shortening and intracellular Ca(2+) transport.

PMID- 22581747
TI  - Mitogen-activated protein kinase is required for the behavioural desensitization
      that occurs after repeated injections of angiotensin II.
AB  - Angiotensin II (Ang II) acts on central angiotensin type 1 (AT(1)) receptors to
      increase water and saline intake. Prolonged exposure to Ang II in cell culture
      models results in a desensitization of the AT(1) receptor that is thought to
      involve receptor internalization, and a behavioural correlate of this
      desensitization has been shown in rats after repeated central injections of Ang
      II. Specifically, rats given repeated injections of Ang II drink less water than
      control animals after a subsequent test injection of Ang II. In the same
      conditions, however, repeated injections of Ang II have no effect on Ang II
      induced saline intake. Given earlier studies indicating that separate
      intracellular signalling pathways mediate Ang II-induced water and saline intake,
      we hypothesized that the desensitization observed in rats may be incomplete,
      leaving the receptor able to activate mitogen-activated protein (MAP) kinases
      (ERK1/2), which play a role in Ang II-induced saline intake without affecting
      water intake. In support of this hypothesis, we found no difference in MAP kinase
      phosphorylation after an Ang II test injection in rats given prior treatment with
      repeated injections of vehicle, Ang II or Sar(1),Ile(4),Ile(8)-Ang II (SII), an
      Ang II analogue that activates MAP kinase without G protein coupling. In
      addition, we found that pretreatment with the MAP kinase inhibitor U0126
      completely blocked the desensitizing effect of repeated Ang II injections on
      water intake. Furthermore, Ang II-induced water intake was reduced to a similar
      extent by repeated injections of Ang II or SII. The results suggest that G
      protein-independent signalling is sufficient to produce behavioural
      desensitization of the angiotensin system and that the desensitization requires
      MAP kinase activation.

PMID- 22581746
TI  - A role for nitric oxide within the nucleus tractus solitarii in the development
      of muscle mechanoreflex dysfunction in hypertension.
AB  - Evidence suggests that the muscle mechanoreflex, a circulatory reflex that raises
      blood pressure and heart rate (HR) upon activation of mechanically sensitive
      afferent fibres in skeletal muscle, is overactive in hypertension. However, the
      mechanisms underlying this abnormal reflex function have yet to be identified.
      Sensory input from the mechanoreflex is processed within the nucleus tractus
      solitarii (NTS) in the medulla oblongata. Within the NTS, the enzymatic activity
      of nitric oxide synthase produces nitric oxide (NO). This centrally derived NO
      has been shown to modulate muscle reflex activity and serves as a viable
      candidate for mediating the mechanoreflex dysfunction that develops in
      hypertension. We hypothesized that mechanoreflex dysfunction in hypertension is
      mediated by abnormal alterations in NO production in the NTS. Mechanically
      sensitive afferent fibres were stimulated by passively stretching hindlimb muscle
      before and after blocking the endogenous production of NO within the NTS via
      microdialysis of the NO synthase inhibitor L-NAME (1 and 5 mM) in normotensive
      Wistar-Kyoto rats and spontaneously hypertensive rats (SHRs). Changes in HR and
      mean arterial pressure in response to stretch were significantly larger in SHRs
      compared with Wistar-Kyoto rats prior to L-NAME dialysis. Attenuating NO
      production via L-NAME in normotensive rats recapitulated the exaggerated
      cardiovascular response to stretch observed in SHRs. Dialysing L-NAME in SHRs
      further accentuated the increases in HR and mean arterial pressure elicited by
      stretch. These findings support the contention that reductions in NO production
      within the NTS contribute to the generation of abnormal cardiovascular control by
      the skeletal muscle mechanoreflex in hypertension.

PMID- 22581748
TI  - Lipopolysaccharide enhances FcepsilonRI-mediated mast cell degranulation by
      increasing Ca2+ entry through store-operated Ca2+ channels: implications for
      lipopolysaccharide exacerbating allergic asthma.
AB  - Lipopolysaccharide (LPS) can exacerbate asthma; however, the mechanisms are not
      fully understood. This study investigated the effect of LPS on antigen-stimulated
      mast cell degranulation and the underlying mechanisms. We found that LPS enhanced
      degranulation in RBL-2H3 cells and mouse peritoneal mast cells upon FcepsilonRI
      activation, in a dose- and time-dependent manner. Parallel to the alteration of
      degranulation, LPS increased FcepsilonRI-activated Ca(2+) mobilization, as well
      as Ca(2+) entry through store-operated calcium channels (SOCs) evoked by
      thapsigargin. Blocking Ca(2+) entry through SOCs completely abolished LPS
      enhancement of mast cell degranulation. Consistent with functional alteration of
      SOCs, LPS increased mRNA and protein levels of Orai1 and STIM1, two major
      subunits of SOCs, in a time-dependent manner. In addition, LPS increased the mRNA
      level of Toll-like receptor 4 (TLR4) in a time-dependent manner. Blocking TLR4
      with Cli-095 inhibited LPS, increasing transcription and expression of SOC
      subunits. Concomitantly, the effect of LPS enhancement of Ca(2+) mobilization and
      mast cell degranulation was largely reduced by Cli-095. Administration of LPS (1
      MUg) in vivo aggravated airway hyperreactivity and inflammatory reactions in
      allergic asthmatic mice. Histamine levels in serum and bronchoalveolar lavage
      fluid were increased by LPS treatment. In addition, Ca(2+) mobilization was
      enhanced in peritoneal mast cells isolated from LPS-treated asthmatic mice. Taken
      together, these results imply that LPS enhances mast cell degranulation, which
      potentially contributes to LPS exacerbating allergic asthma. Lipopolysaccharide
      increases Ca(2+) entry through SOCs by upregulating transcription and expression
      of SOC subunits, mainly through interacting with TLR4 in mast cells, resulting in
      enhancement of mast cell degranulation upon antigen stimulation.

PMID- 22581749
TI  - Autonomic neuroimmunomodulation in chagasic cardiomyopathy.
AB  - Chagas disease is an endemic parasitic disease, caused by the flagellate
      protozoan Trypanosoma cruzi, with a high prevalence in Latin America. During its
      chronic phase, chronic chagasic cardiomyopathy is the most apparent clinical
      form, affecting 25-30% of patients. This clinical form may present as congestive
      heart failure, thromboembolic phenomena, cardiac arrhythmias and sudden death.
      Pathological findings in the heart include mononuclear inflammatory infiltrate,
      focal myocarditis, epicarditis and neuroganglionitis, associated with variable
      focal fibrosis and widely variable autonomic dysfunction. The immune-inflammatory
      response has been considered to be the cause of the autonomic dysfunction, which
      may trigger life-threatening arrhythmias and sudden death. In the last few years,
      several reports in the literature have described the marked role played by the
      autonomic nervous system in the modulation of the immune-inflammatory response in
      some experimental models of infectious, ischaemic and autoimmune diseases.
      However, nothing is known about this autonomic neural modulation of the immune
      response in Chagas disease. In the present report, we discuss several sets of
      evidence suggesting that changes in the autonomic drive directed towards the
      heart could modify blood and tissue parasitism, as well as inflammatory
      infiltration, in chagasic cardiomyopathy. The pathogenic implications of these
      potential neural immune manipulations are also discussed.

PMID- 22581750
TI  - Noxious somatic stimuli diminish respiratory-sympathetic coupling by selective
      resetting of the respiratory rhythm in anaesthetized rats.
AB  - Noxious somatic stimulation evokes respiratory and autonomic responses. The
      mechanisms underlying the responses and the manner in which they are co-ordinated
      are still unclear. The effects of activation of somatic nociceptive fibres on
      lumbar sympathetic nerve activity at slow (2-10 Hz) and fast frequency bands (100
      1000 Hz) and the effects on respiratory-sympathetic coupling are unknown. In
      anaesthetized, artificially ventilated Sprague-Dawley rats under neuromuscular
      blockade, ensemble averaging of sympathetic activity following high-intensity
      single-pulse stimulation of the sciatic nerve revealed two peaks (~140 and ~250
      ms) that were present at similar latencies whether or not slow or fast band
      filtering was used. Additionally, in the slow band of both lumbar and splanchnic
      sympathetic nerve activity, a third peak with a very slow latency (~650 ms) was
      apparent. In the respiratory system, activation of the sciatic nerve decreased
      the expiratory period when the stimulus occurred during the first half of
      expiration, but increased the expiratory period if the stimulus was delivered in
      the second half of the expiratory phase. The phase shifting of the respiratory
      cycle also impaired the respiratory-sympathetic coupling in both splanchnic and
      lumbar sympathetic nerve activity in the subsequent respiratory cycle. The
      findings suggest that noxious somatosympathetic responses reduce the co
      ordination between respiration and perfusion by resetting the respiratory pattern
      generator.

PMID- 22581752
TI  - Apparent transmission distortion of a pericentric chromosome one inversion in a
      large multi-generation pedigree.
AB  - Pericentric chromosome inversions are often associated with infertility,
      recurrent pregnancy loss, and an increased risk for offspring with congenital
      anomalies. We report on a chromosome 1 inversion between 1p36.21 and 1q42.13, one
      of the largest described familial pericentric inversions of chromosome 1. The
      inversion was ascertained following the birth of a female with multiple
      congenital anomalies due to a recombinant chromosome 1. The inversion was
      subsequently detected or inferred in 16 healthy individuals over five
      generations. Interestingly, with a ratio of 16 carriers to 6 noncarriers, there
      appears to be transmission distortion of the inverted chromosome 1 within the
      family. Although there is no reported difficulty conceiving in the family, the
      risk of miscarriage is higher than predicted at 34% (13/38). The recurrence risk
      of a recombinant chromosome also appears to be lower than expected based on the
      mode of ascertainment. This case contributes to the spectrum of clinical features
      of chromosome 1 recombinants and raises the question of whether or not there is a
      selective advantage of the inverted chromosome at meiosis, conception, or post
      zygotically that has contributed to transmission distortion of the inverted
      chromosome.

PMID- 22581751
TI  - Prevalidation of a human cornea construct as an alternative to animal corneas for
      in vitro drug absorption studies.
AB  - The use of ophthalmic drugs has increased consistently over the past few decades.
      Currently, most research is conducted using in vivo and ex vivo animal
      experiments; however, they have many disadvantages, including ethical concerns,
      high costs, the questionable extension of animal results to humans, and poor
      standardization. Although several cell culture-based cornea models have been
      developed, none have been validated and accepted for general use. In this study,
      a standardized, three-dimensional model of the human cornea (Hemicornea, HC)
      based on immortalized human corneal cells and cultivated in serum-free conditions
      was developed for drug absorption studies and prevalidated using compounds with a
      wide range of molecular characteristics (sodium fluorescein, rhodamine B,
      fluorescein isothiocyanate-labeled dextran, aciclovir, bimatoprost,
      dexamethasone, and timolol maleate). The HC model was independently cultured in
      three different laboratories, and the intralaboratory and interlaboratory
      reproducibility was analyzed and compared with the rabbit cornea. This analysis
      showed that the HC has a barrier in the same range as excised animal corneas,
      although with a higher reproducibility and lower variability. Because of the
      demonstrated transferability, the HC represents a promising in vitro alternative
      to the use of ex vivo tissue and offers a well-defined and standardized system
      for drug absorption studies.

PMID- 22581753
TI  - Discovery of 3H-imidazo[4,5-b]pyridines as potent c-Met kinase inhibitors:
      design, synthesis, and biological evaluation.
AB  - To identify novel c-Met inhibitors, sequences and crystal structures of the human
      kinome were analyzed to find interesting hinge binders that have been
      underexplored within the tyrosine kinase subfamily. Through this study, the
      imidazolopyridine ring was selected as a novel c-Met hinge-binding inhibitor
      scaffold. A series of derivatives was prepared, and the structure-activity
      relationships were studied. Among these, one compound in particular showed
      excellent activities in enzymatic and cellular assays, good in vitro metabolic
      stability, and favorable pharmacokinetic parameters. When administered orally,
      the compound inhibited tumor growth in an NIH-3T3/TPR-Met xenograft model and did
      not show adverse effects on body weight. The present work not only conceptually
      demonstrates a new route for designing novel kinase inhibitors by using known
      structural information of ligand-hinge interactions but also provides a series of
      imidazolopyridine derivatives as potent c-Met inhibitors.

PMID- 22581754
TI  - Subject movement during multislice interleaved MR acquisitions: prevalence and
      potential effect on MRI-derived brain pathology measurements and multicenter
      clinical trials of therapeutics for multiple sclerosis.
AB  - PURPOSE: To show the prevalence of inter-packet motion in clinical trial magnetic
      resonance imaging (MRI) data and the effect of inter-packet motion on MRI-derived
      brain pathology measurements. MATERIALS AND METHODS: We present a method to
      detect and quantify inter-packet motion, apply it to 2384 MRIs to determine the
      prevalence of inter-packet motion in clinical trial data, and show the effect of
      inter-packet motion on measuring multiple sclerosis (MS) lesion volumes. RESULTS:
      Experiments with simulated data showed that the detection procedure was accurate
      at measuring the amount of movement between packets and quantifying the amount of
      missing data. Application to clinical trial data demonstrated that a large number
      of MRIs had missing data due to inter-packet motion; 20% of the images had
      greater than 10% of the data missing and 10% of the images had greater than 15%
      of the data missing. These levels corresponded to thresholds where lesions were
      difficult to visually identify or disappeared completely. Lesion volume
      measurement errors ranged from 1.3 +/- 0.5% to 9.9 +/- 6.3%. CONCLUSION: Inter
      packet motion can introduce substantial errors to MRI-derived brain pathology
      measurements. The prevalence of inter-packet motion is substantial in MS clinical
      trial data. Automated detection procedures should be implemented to increase the
      fidelity of MRI-derived measurements.

PMID- 22581755
TI  - Differential catalytic action of Brevibacillus laterosporus on two dissimilar azo
      dyes Remazol red and Rubine GFL.
AB  - This comparative study disclosed the diverse catalytic activities of
      Brevibacillus laterosporus on two different azo dyes. It decolorized 100% of
      Remazol red and 95% of Rubine GFL within 30 and 48 h respectively, under static
      condition at 50 mg l-1 dye concentration. Significant increase was observed in
      azo reductase, NADH-DCIP reductase, veratryl alcohol oxidase and tyrosinase in
      cells obtained after decolorization of Remazol red; whereas these values were
      much different with complete inhibition of azo reductase during decolorization of
      Rubine GFL. The plausible pathway of dye degradation obtained from Gas
      chromatography-Mass spectroscopy (GC-MS) data confirmed the different metabolic
      fate of these structurally unidentical dyes. FTIR and HPTLC analysis of extracted
      metabolites confirmed the biodegradation, while phytotoxicity study assured the
      detoxification of both the dyes studied. The results obtained in this study
      suggests, i) sulpho and hydroxyl group present at ortho position to azo group
      stimulated reduction of azo bond by azo reductase in Remazol red, ii) the same
      reduction was totally hampered due to presence of ethyl-amino propanenitrile
      group at para position to azo group in Rubine GFL.

PMID- 22581756
TI  - Macroscopic and microscopic analysis of the tongue of the common opossum
      (Didelphis marsupialis).
AB  - We performed a macroscopic and microscopic study of the tongues of common
      opossums, Didelphis marsupialis, from South America. We studied two males and two
      females. We collected morphometric data on the tongue with precision calipers.
      For the light microscopy and scanning electron microscopy analyses, we fixed
      tissue fragments in 10% formaldehyde and 2.5% glutaraldehyde, respectively. The
      opossum tongues averaged 5.87 +/- 0.20 cm in length, 3.27 +/- 0.15 cm in width at
      the lingual body, and 3.82 +/- 0.15 cm in width at the root. The mean thickness
      of the lingual body was 1.8 +/- 0.1 cm, and the thickness of the root was 3.82 +/
      0.15 cm. Sharp filiform papillae were scattered across the entire tongue;
      conical filiform papillae occurred on the lingual body and tongue tip; fungiform
      papillae were scattered among the filiform papillae on the lingual body and
      tongue tip; and there were three vallate papillae at the root of the tongue. We
      found two strands of papillary projections in the tongue root. Despite the low
      variability observed in the lingual papillae, the morphological data obtained in
      this study may be related to the opossum's diverse food habits and the extensive
      geographic distribution of the species throughout America.

PMID- 22581758
TI  - Two-dimensional nanostructured growth of nanoclusters and molecules on insulating
      surfaces.
AB  - Noncontact atomic force microscopy (nc-AFM), Kelvin probe force microscopy (KPFM)
      and first principle calculations show that the nanostructured (001) Suzuki
      surface of Cd(2+) doped NaCl can be used to confine the growth of palladium
      clusters and functionalized brominated pentahelicene molecules into only the
      Suzuki regions, which contain the impurities. The Suzuki surface is an ideal
      model surface for nanostructuring metal clusters and molecules.

PMID- 22581757
TI  - Acute and medium-term outcomes of endovascular therapy of obstructive disease of
      diverse etiology of the common femoral artery.
AB  - BACKGROUND: Common femoral endarterectomy is regarded as the standard
      revascularization strategy for the treatment of common femoral artery (CFA)
      disease. The availability of a variety of endovascular tools has resulted in an
      increased number of patients with CFA disease being treated using an endovascular
      strategy. We sought to evaluate clinical outcomes in a contemporary series of
      patients who were treated for CFA disease using an endovascular-first approach.
      METHODS: All patients with obstructive CFA disease who were treated using
      endovascular therapy were retrospectively identified from a peripheral
      interventional database. Baseline patient characteristics, anatomic details,
      procedural data, and clinical outcomes were assessed. Kaplan-Meier (KM) curves
      for mortality, amputation-free survival, and primary and secondary patency were
      generated. RESULTS: Between 2006 and 2011, a total of 30 patients underwent 31
      CFA procedures. The primary etiologies of CFA obstruction were atherosclerosis
      (58%), access-site-related complication (32%), and thromboembolism (10%).
      Patients presented with severe claudication (60%), critical limb ischemia (13%),
      or acute limb ischemia (27%). The procedure was technically successful in 90% of
      cases with major complications in two (7%) patients. There was no procedure
      related mortality. The KM estimate of survival and amputation-free survival at 1
      year was 96% (+/- 4%) and 96% (+/- 4%), respectively. In those patients who had a
      successful revascularization, the overall 1-year estimate for primary and
      secondary patency was 88% (+/- 6) and 92% (+/- 5%), respectively. There was a
      nonsignificant trend toward lower patency in patients treated for atherosclerotic
      disease compared to those with access-site-related complications and
      thromboembolic disease at 2-year follow-up (76 vs. 100%, P = 0.08). CONCLUSIONS:
      Endovascular therapy for treatment of obstructive disease of the CFA is
      associated with a high rate of acute technical success. Primary patency rates in
      the cohort treated for access-site-related complications and thromboembolic
      disease are excellent and support an endovascular-first approach for this patient
      subset. Based on lower patency rates, surgical endarterectomy for the treatment
      of atherosclerotic disease in the CFA remains the gold standard in patients with
      normal surgical risk.

PMID- 22581759
TI  - Comparative canine pharmacokinetics-pharmacodynamics of fospropofol disodium
      injection, propofol emulsion, and cyclodextrin-enabled propofol solution
      following bolus parenteral administration.
AB  - The pharmacokinetics and pharmacodynamics of fospropofol (FP) disodium injection,
      propofol emulsion (PE), and cyclodextrin-enabled propofol (CDP) solution
      following bolus parenteral administration in dogs was evaluated. Three healthy
      male beagle dogs were treated in a three-way cross-over study (14 day washout
      period) with 6 mg/kg propofol equivalents. Blood samples were collected predose
      and at 16 points postdose through 1440 min and analyzed for propofol and FP, when
      appropriate. From 5 min predose to 30 min postdose, brain electrical activity
      [electroencephalography (EEG)] was recorded and analyzed by power spectrum
      analysis techniques. Each formulation appeared to be well tolerated with
      transient discomfort observed in the PE and CDP animals and minor excitability in
      the FP animals prior to loss of consciousness. Blood propofol followed three
      compartment pharmacokinetic behavior and derived parameters were not
      statistically different except for elimination half-life from the CDP formulation
      and onset, and duration of anesthesia from the FP formulation. The effect site
      concentrations at 50% the maximum EEG effect for the FP and CDP formulations were
      approximately one-half that of the PE formulation. Onset and duration of
      anesthesia are correlated with modeled effect site propofol concentrations. The
      implications of formulation on pain on injection and propofol activity are
      discussed.

PMID- 22581760
TI  - Hornstein-Birt-Hogg-Dube syndrome: a renaming and reconsideration.
AB  - The so-called Birt-Hogg-Dube syndrome, an autosomal dominant trait characterized
      by multiple fibrofolliculomas and extracutaneous cancer proneness, was not first
      recognized by Birt, Hogg, and Dube. Hence, the presently used eponymic
      designation reflects a historical error. In fact, the disorder was discovered in
      the following way. In 1975, Hornstein and Knickenberg described a "distinct
      nosological entity" in two sibs with multiple perifollicular fibromas, multiple
      skin tags, and polyps of the colon with a tendency to malignancy. The father had
      similar skin lesions and "bilateral kidney cysts" and unilateral lung cysts. In
      1976, Hornstein et al. informed, in two additional articles, both geneticists and
      gastroenterologists about the new autosomal dominant trait. When Birt et al.
      presented their report in 1977, they knew of Hornstein's first publication but
      were convinced that they had discovered "a previously unrecognized hereditary
      pilar hamartoma." This was a misconception because what they called
      "fibrofolliculoma" has turned out to be identical with "perifollicular fibroma"
      as described by Hornstein et al. Moreover, Birt et al. failed to mention any
      associated extracutaneous cancer proneness, whereas Hornstein et al. had
      delineated the complete syndrome. For all of these reasons, the new term
      "Hornstein-Birt-Hogg-Dube syndrome" appears to be appropriate.

PMID- 22581761
TI  - Extract of white button mushroom affects skin healing and angiogenesis.
AB  - White button mushroom extract was examined in this study on (1) its potential
      effect on angiogenesis in chorioallantoic culture and (2) its recovering effect
      on the skin after injury in the ICR mice. Methods used included TUNEL assay on
      apoptosis, immunohistochemistry for vascular endothelial growth factor (VEGF),
      proliferative cell nuclear antigen (PCNA), epidermal growth factor (EGF),
      transforming growth factor beta (TGF-beta), and immune factor CD4 and western
      blotting. The results of chorioallantoic culture showed that the mushroom
      treatment led to significant increase in densities of VEGF sites. In the skin
      injury, ICR mice model increased EGF, PCNA, and collagen fibers, along with
      decrease of TUNEL positive apoptotic cells and limited reaction of TGF-beta and
      CD4 indicated that white button mushroom extract appeared to have beneficial
      effects on skin in regeneration and after injury.

PMID- 22581762
TI  - Correlation of volume transfer coefficient Ktrans with histopathologic grades of
      gliomas.
AB  - PURPOSE: To evaluate the roles of dynamic contrast-enhanced magnetic resonance
      imaging (DCE-MRI) and optimum tracer kinetic parameters in the noninvasive
      grading of the glial brain tumors with histopathological grades (I-IV). MATERIALS
      AND METHODS: Twenty-eight patients with histopathologically graded gliomas were
      imaged. Images with five flip angles were acquired before injection of gadolinium
      DTPA and were processed to calculate the T(1) value of each region of interest
      (ROI). All the DCE-MRI data acquired during the injection were processed based on
      the MRI signal and pharmacokinetic models to establish concentration-time curves
      in the ROIs drawn within the tumors, contralateral normal areas, and area of the
      individual artery input functions (iAIF) of each patient. A nonlinear least
      square-fitting method was used to obtain tracer kinetic parameters. Kruskal
      Wallis H-test and Mann-Whitney U-test were applied to these parameters in
      different histopathological grade groups for statistical differences (P < 0.05).
      RESULTS: Volume transfer coefficient (K(trans) ) and extravascular extracellular
      space volume fraction (V(e) ) calculated using iAIFs can be used not only to
      distinguish the low (ie, I and II) from the high (ie, III and IV) grade gliomas
      (P( Ktrans) < 0.001 and P(Ve) < 0.001), but also grade II from III (P( Ktrans) =
      0.016 and P(Ve) = 0.033). CONCLUSION: K(trans) is the most sensitive and specific
      parameter in noninvasive grading, distinguishing the high (III and IV) from the
      low (I and II) grade and high grade III from low grade II gliomas.

PMID- 22581763
TI  - Assessment of safety, accuracy, and human CD34+ cell retention after
      intramyocardial injections with a helical needle catheter in a porcine model.
AB  - OBJECTIVES: Assess accuracy of Helix injections via fluoroscopic-mapping and
      evaluate delivery safety. BACKGROUND: Percutaneous intramyocardial-delivery of
      agents must be safe and accurate; retention is also important. A delivery system
      (Helical Infusion/Morph Guide-Catheter, Biocardia Inc) has been developed to
      improve maneuverability and stability of catheter-needle-myocardium intersection.
      METHODS: Accuracy and safety: 12 swine underwent LV and coronary angiography via
      8F sheath. Targeted delivery was assigned into LAD, LCX, or RCA. System was
      advanced into LV and 6 targeted intramyocardial dye injections (5 mm apart)
      delivered using fluoroscopy. After euthanization, hearts underwent gross and
      histologic evaluation. Retention was assessed by iron-oxide and fluorochrome
      labeled CD34+ cells. Cells were injected into 6 swine using same techniques.
      Delivery system was advanced into LV, and injections delivered using fluoroscopy.
      Euthanization was performed at 2 hr and hearts formalin fixed. MRI was performed
      on 6 treated hearts and 4 untreated controls. Blinded analysis performed by 2
      radiologists. Two treated hearts underwent immunohistological analysis. RESULTS:
      Accuracy and safety evaluation: 71/72 injections (98.6%) were within prespecified
      zone; 7/72 (9.7%) less than 5 mm apart. No adverse events occurred. MRI-presence
      of iron-oxide labeled CD34+ cells were correctly identified in 95% (19/20) of
      imaged injections. Anti-CD34+ antibody staining and fluorescence microscopy
      confirmed CD34+ cells in myocardium. Histology confirmed cell viability at
      fixation. CONCLUSIONS: Helix system was accurate and safe. Retention of CD34+
      cells was confirmed by MRI and immunohistology. Further preclinical studies are
      needed to characterize retention over time and quantify efficiency. Studies are
      needed to confirm accuracy, safety, and retention in humans.

PMID- 22581764
TI  - Bioavailability of pharmaceuticals in waters close to wastewater treatment
      plants: use of fish bile for exposure assessment.
AB  - Pharmaceuticals are ubiquitous in surface waters as a consequence of discharges
      from municipal wastewater treatment plants. However, few studies have assessed
      the bioavailability of pharmaceuticals to fish in natural waters. In the present
      study, passive samplers and rainbow trout were experimentally deployed next to
      three municipal wastewater treatment plants in Finland to evaluate the degree of
      animal exposure. Pharmaceuticals from several therapeutic classes (in total 15)
      were analyzed by liquid chromatography-tandem mass spectrometry in extracts of
      passive samplers and in bile and blood plasma of rainbow trout held at polluted
      sites for 10 d. Each approach indicated the highest exposure near wastewater
      treatment plant A and the lowest near that of plant C. Diclofenac, naproxen, and
      ibuprofen were found in rainbow trout, and their concentrations in bile were 10
      to 400 times higher than in plasma. The phase I metabolite hydroxydiclofenac was
      also detected in bile. Hence, bile proved to be an excellent sample matrix for
      the exposure assessment of fish. Most of the monitored pharmaceuticals were found
      in passive samplers, implying that they may overestimate the actual exposure of
      fish in receiving waters. Two biomarkers, hepatic vitellogenin and cytochrome
      P4501A, did not reveal clear effects on fish, although a small induction of
      vitellogenin mRNA was observed in trout caged near wastewater treatment plants B
      and C.

PMID- 22581765
TI  - The prospect of FKBP51 as a drug target.
AB  - The FK506 binding protein 51 (FKBP51) is best known as an Hsp90-associated co
      chaperone that regulates the responsiveness of steroid hormone receptors. In
      human genetic association studies, FKBP51 has repeatedly been associated with
      emotion processing and numerous stress-related affective disorders. It has also
      been implicated in contributing to the glucocorticoid hyposensitivity observed in
      New World primates. More recently, several research groups have consistently
      shown a protective effect of FKBP51 knockout or knockdown on stress endocrinology
      and stress-coping behavior in animal models of depression and anxiety. The
      principal druggability of FKBP51 is exemplified by the prototypic FKBP ligands
      FK506 and rapamycin. Moreover, FKBP51 is highly suited for X-ray co
      crystallography, which should facilitate the rational drug design of improved
      FKBP51 ligands. In summary, FKBP51 has emerged as a promising new drug target for
      stress-related disorders that should be amenable to drug discovery.

PMID- 22581766
TI  - Thiazole-based organic semiconductors for organic electronics.
AB  - Over the past two decades, organic semiconductors have been the subject of
      intensive academic and commercial interests. Thiazole is a common electron
      accepting heterocycle due to electron-withdrawing nitrogen of imine (C=N),
      several moieties based on thiazole have been widely introduced into organic
      semiconductors, and yielded high performance in organic electronic devices. This
      article reviews recent developments in the area of thiazole-based organic
      semiconductors, particularly thiazole, bithiazole, thiazolothiazole and
      benzobisthiazole-based small molecules and polymers, for applications in organic
      field-effect transistors, solar cells and light-emitting diodes. The remaining
      problems and challenges, and the key research direction in near future are
      discussed.

PMID- 22581767
TI  - Molecular epidemiology of carbapenem-resistant Acinetobacter spp. from XiangYa
      Hospital, in Hunan Province, China.
AB  - Carbapenem-resistant Acinetobacter baumannii has been known as an opportunistic
      pathogen that causes a variety of illness worldwide. In this study, we
      characterize the molecular epidemiology of 174 non-repetitive clinical isolates
      of A. baumannii collected from January to June 2009 from Xiangya Hospital, in
      Hunan Province, China, including an outbreak period of A. baumannii. These 174
      isolates harbored A. baumannii intrinsic gene OXA-51. They were resistant to
      multiple antibiotics with resistance rates as 49.4% to imipenem, 48.3% to
      meropenem, 46.6% to ampicillin-sulbactam, 6.9% to cefoperazone-sulbactam, and
      6.3% to minocycline. 74 out of 174 isolates were identified as carbapenemase
      producing strains, among which bla(OXA-23)  gene was found in 71 isolates. These
      74 carbapenemase expression strains could be divided into four genotypes by
      enterobacterial repetitive intergenic consensus (ERIC)-PCR, with 19, 17, 33 and 5
      clones in each group. We also found four imipenem resistant isolates carrying OXA
      23 gene without showing carbapenemase phenotype. Our findings show that the
      bla(OXA-23)  gene is the common carbapenemase gene among carbapenem-resistant
      Acinetobacter spp. isolates, suggesting that clonal spread of carbapenemase
      producing isolates may be one important factor which results in the high
      carbapenem resistance rate in the local hospital in Hunan Province, China.

PMID- 22581768
TI  - PEP-FOLD: an updated de novo structure prediction server for both linear and
      disulfide bonded cyclic peptides.
AB  - In the context of the renewed interest of peptides as therapeutics, it is
      important to have an on-line resource for 3D structure prediction of peptides
      with well-defined structures in aqueous solution. We present an updated version
      of PEP-FOLD allowing the treatment of both linear and disulphide bonded cyclic
      peptides with 9-36 amino acids. The server makes possible to define disulphide
      bonds and any residue-residue proximity under the guidance of the biologists.
      Using a benchmark of 34 cyclic peptides with one, two and three disulphide bonds,
      the best PEP-FOLD models deviate by an average RMS of 2.75 A from the full NMR
      structures. Using a benchmark of 37 linear peptides, PEP-FOLD locates lowest
      energy conformations deviating by 3 A RMS from the NMR rigid cores. The evolution
      of PEP-FOLD comes as a new on-line service to supersede the previous server. The
      server is available at: http://bioserv.rpbs.univ-paris-diderot.fr/PEP-FOLD.

PMID- 22581770
TI  - Bulged DNA substrates for identifying poxvirus resolvase inhibitors.
AB  - Resolvase enzymes that cleave DNA four-way (Holliday) junctions are required for
      poxvirus replication, but clinically useful inhibitors have not been developed.
      Here, we report an assay for resolvase cleavage activity based on fluorescence
      polarization (FP) for high-throughput screening and mechanistic studies. Initial
      analysis showed that cleavage of a fluorescently labeled Holliday junction
      substrate did not yield an appreciable change in FP, probably because the
      cleavage product did not have sufficiently increased mobility to yield a strong
      FP signal. Iterative optimization yielded a substrate with an off-center DNA
      bulge, which after cleavage released a labeled short stand and yielded a greatly
      reduced FP signal. Using this assay, 133,000 compounds were screened, identifying
      1-hydroxy-1,8-naphthyridin-2(1H)-one compounds as inhibitors. Structure-activity
      studies revealed functional parallels to Food and Drug Administration (FDA)
      approved drugs targeting the related human immunodeficiency virus integrase
      enzyme. Some 1-hydroxy-1,8-naphthyridin-2(1H)-one compounds showed anti-poxvirus
      activity.

PMID- 22581769
TI  - Topological characterization of the DnaA-oriC complex using single-molecule
      nanomanipuation.
AB  - In most bacteria, the timing and synchrony of initiation of chromosomal
      replication are determined by the binding of the AAA(+) protein DnaA to a set of
      high- and low-affinity sites found within the origin of chromosomal replication
      (oriC). Despite the large amount of information on the role and regulation of
      DnaA, the actual structure of the DnaA-oriC complex and the mechanism by which it
      primes the origin for the initiation of replication remain unclear. In this
      study, we have performed magnetic tweezers experiments to investigate the
      structural properties of the DnaA-oriC complex. We show that the DnaA-ATP-oriC
      complex adopts a right-handed helical conformation involving a variable amount of
      DNA and protein whose features fit qualitatively as well as quantitatively with
      an existing model based on the crystal structure of a truncated DnaA tetramer
      obtained in the absence of DNA. We also investigate the topological effect of
      oriC's DNA unwinding element.

PMID- 22581771
TI  - Endogenous formation and repair of oxidatively induced G[8-5 m]T intrastrand
      cross-link lesion.
AB  - Exposure to reactive oxygen species (ROS) can give rise to the formation of
      various DNA damage products. Among them, d(G[8-5 m]T) can be induced in isolated
      DNA treated with Fenton reagents and in cultured human cells exposed to gamma
      rays, d(G[8-5m]T) can be recognized and incised by purified Escherichia coli
      UvrABC nuclease. However, it remains unexplored whether d(G[8-5 m]T) accumulates
      in mammalian tissues and whether it is a substrate for nucleotide excision repair
      (NER) in vivo. Here, we found that d(G[8-5 m]T) could be detected in DNA isolated
      from tissues of healthy humans and animals, and elevated endogenous ROS
      generation enhanced the accumulation of this lesion in tissues of a rat model of
      Wilson's disease. Additionally, XPA-deficient human brain and mouse liver as well
      as various types of tissues of ERCC1-deficient mice contained higher levels of
      d(G[8-5 m]T) but not ROS-induced single-nucleobase lesions than the corresponding
      normal controls. Together, our studies established that d(G[8-5 m]T) can be
      induced endogenously in mammalian tissues and constitutes a substrate for NER in
      vivo.

PMID- 22581772
TI  - The magnitude and colour of noise in genetic negative feedback systems.
AB  - The comparative ability of transcriptional and small RNA-mediated negative
      feedback to control fluctuations or 'noise' in gene expression remains
      unexplored. Both autoregulatory mechanisms usually suppress the average (mean) of
      the protein level and its variability across cells. The variance of the number of
      proteins per molecule of mean expression is also typically reduced compared with
      the unregulated system, but is almost never below the value of one. This relative
      variance often substantially exceeds a recently obtained, theoretical lower limit
      for biochemical feedback systems. Adding the transcriptional or small RNA
      mediated control has different effects. Transcriptional autorepression robustly
      reduces both the relative variance and persistence (lifetime) of fluctuations.
      Both benefits combine to reduce noise in downstream gene expression.
      Autorepression via small RNA can achieve more extreme noise reduction and
      typically has less effect on the mean expression level. However, it is often more
      costly to implement and is more sensitive to rate parameters. Theoretical lower
      limits on the relative variance are known to decrease slowly as a measure of the
      cost per molecule of mean expression increases. However, the proportional
      increase in cost to achieve substantial noise suppression can be different away
      from the optimal frontier-for transcriptional autorepression, it is frequently
      negligible.

PMID- 22581774
TI  - Using a priori knowledge to align sequencing reads to their exact genomic
      position.
AB  - The use of a priori knowledge in the alignment of targeted sequencing data is
      investigated using computational experiments. Adapting a Needleman-Wunsch
      algorithm to incorporate the genomic position information from the targeted
      capture, we demonstrate that alignment can be done to just the target region of
      interest. When in addition use is made of direct string comparison, an
      improvement of up to a factor of 8 in alignment speed compared to the fastest
      conventional aligner (Bowtie) is obtained. This results in a total alignment time
      in targeted sequencing of around 7 min for aligning approximately 56 million
      captured reads. For conventional aligners such as Bowtie, BWA or MAQ, alignment
      to just the target region is not feasible as experiments show that this leads to
      an additional 88% SNP calls, the vast majority of which are false positives (~
      92%).

PMID- 22581773
TI  - The FleQ protein from Pseudomonas aeruginosa functions as both a repressor and an
      activator to control gene expression from the pel operon promoter in response to
      c-di-GMP.
AB  - Bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) modulates the
      transition between planktonic and biofilm life styles. In response to c-di-GMP,
      the enhancer binding protein FleQ from Pseudomonas aeruginosa derepresses the
      expression of Pel exopolysaccharide genes required for biofilm formation when a
      second protein, FleN is present. A model is that binding of c-di-GMP to FleQ
      induces its dissociation from the pelA promoter allowing RNA polymerase to access
      this site. To test this, we analyzed pelA DNA footprinting patterns with various
      combinations of FleQ, FleN and c-di-GMP, coupled to in vivo promoter activities.
      FleQ binds to two sites called box 1 and 2. FleN binds to FleQ bound at these
      sites causing the intervening DNA to bend. Binding of c-di-GMP to FleQ relieves
      the DNA distortion but FleQ remains bound to the two sites. Analysis of wild type
      and mutated versions of pelA-lacZ transcriptional fusions suggests that FleQ
      represses gene expression from box 2 and activates gene expression in response to
      c-di-GMP from box 1. The role of c-di-GMP is thus to convert FleQ from a
      repressor to an activator. The mechanism of action of FleQ is distinct from that
      of other bacterial transcription factors that both activate and repress gene
      expression from a single promoter.

PMID- 22581775
TI  - Codon usage bias in prokaryotic pyrimidine-ending codons is associated with the
      degeneracy of the encoded amino acids.
AB  - Synonymous codons are unevenly distributed among genes, a phenomenon termed codon
      usage bias. Understanding the patterns of codon bias and the forces shaping them
      is a major step towards elucidating the adaptive advantage codon choice can
      confer at the level of individual genes and organisms. Here, we perform a large
      scale analysis to assess codon usage bias pattern of pyrimidine-ending codons in
      highly expressed genes in prokaryotes. We find a bias pattern linked to the
      degeneracy of the encoded amino acid. Specifically, we show that codon-pairs that
      encode two- and three-fold degenerate amino acids are biased towards the C-ending
      codon while codons encoding four-fold degenerate amino acids are biased towards
      the U-ending codon. This codon usage pattern is widespread in prokaryotes, and
      its strength is correlated with translational selection both within and between
      organisms. We show that this bias is associated with an improved correspondence
      with the tRNA pool, avoidance of mis-incorporation errors during translation and
      moderate stability of codon-anticodon interaction, all consistent with more
      efficient translation.

PMID- 22581776
TI  - Engineering synthetic TAL effectors with orthogonal target sites.
AB  - The ability to engineer biological circuits that process and respond to complex
      cellular signals has the potential to impact many areas of biology and medicine.
      Transcriptional activator-like effectors (TALEs) have emerged as an attractive
      component for engineering these circuits, as TALEs can be designed de novo to
      target a given DNA sequence. Currently, however, the use of TALEs is limited by
      degeneracy in the site-specific manner by which they recognize DNA. Here, we
      propose an algorithm to computationally address this problem. We apply our
      algorithm to design 180 TALEs targeting 20 bp cognate binding sites that are at
      least 3 nt mismatches away from all 20 bp sequences in putative 2 kb human
      promoter regions. We generated eight of these synthetic TALE activators and
      showed that each is able to activate transcription from a targeted reporter.
      Importantly, we show that these proteins do not activate synthetic reporters
      containing mismatches similar to those present in the genome nor a set of
      endogenous genes predicted to be the most likely targets in vivo. Finally, we
      generated and characterized TALE repressors comprised of our orthogonal DNA
      binding domains and further combined them with shRNAs to accomplish near complete
      repression of target gene expression.

PMID- 22581778
TI  - The histone demethylase Kdm3a is essential to progression through
      differentiation.
AB  - Histone demethylation has important roles in regulating gene expression and forms
      part of the epigenetic memory system that regulates cell fate and identity by
      still poorly understood mechanisms. Here, we examined the role of histone
      demethylase Kdm3a during cell differentiation, showing that Kdm3a is essential
      for differentiation into parietal endoderm-like (PE) cells in the F9 mouse
      embryonal carcinoma model. We identified a number of target genes regulated by
      Kdm3a during endoderm differentiation; among the most dysregulated were the three
      developmental master regulators Dab2, Pdlim4 and FoxQ1. We show that
      dysregulation of the expression of these genes correlates with Kdm3a H3K9me2
      demethylase activity. We further demonstrate that either Dab2 depletion or Kdm3a
      depletion prevents F9 cells from fully differentiating into PE cells, but that
      ectopic expression of Dab2 cannot compensate for Kdm3a knockdown; Dab2 is thus
      necessary, but insufficient on its own, to promote complete terminal
      differentiation. We conclude that Kdm3a plays a crucial role in progression
      through PE differentiation by regulating expression of a set of endoderm
      differentiation master genes. The emergence of Kdm3a as a key modulator of cell
      fate decision strengthens the view that histone demethylases are essential to
      cell differentiation.

PMID- 22581781
TI  - Flightless I is a focal adhesion-associated actin-capping protein that regulates
      cell migration.
AB  - The role of adhesion-associated actin-binding proteins in cell migration is not
      well defined. In mouse fibroblasts we screened for focal adhesion-associated
      proteins that were isolated with collagen-coated beads and detected by tandem
      mass spectrometry. We identified flightless I (FliI) as an actin-binding protein
      in focal adhesion fractions, which was verified by immunoblotting. By confocal
      microscopy most FliI was distributed throughout the cytosol and in focal
      adhesions. By sedimentation assays and in vitro binding assays, we found that
      FliI associates with actin filaments and actin monomers. Assays using purified
      proteins showed that FliI inhibits actin polymerization and caps but does not
      sever actin filaments. Cells with FliI knockdown or cells overexpressing FliI
      migrated more or less rapidly, respectively, than wild-type controls. Compared
      with controls, cells with FliI knockdown were less adherent than wild-type cells,
      exhibited reduced numbers of focal adhesions containing activated beta1 integrins
      and vinculin, and exhibited increased incorporation of actin monomers into
      nascent filaments at focal adhesions. These data indicate that FliI regulates
      cell migration through its localization to focal adhesions and its ability to cap
      actin filaments, which collectively affect focal adhesion maturation.

PMID- 22581779
TI  - Neuronal expression of Fig4 is both necessary and sufficient to prevent
      spongiform neurodegeneration.
AB  - FIG4 is a ubiquitously expressed phosphatase that, in complex with FAB1/PIKFYVE
      and VAC14, regulates the biosynthesis of the signaling lipid PI(3,5)P(2). Null
      mutation of Fig4 in the mouse results in spongiform degeneration of brain and
      peripheral ganglia, defective myelination and juvenile lethality. Partial loss-of
      function of human FIG4 results in a severe form of Charcot-Marie-Tooth
      neuropathy. Neurons from null mice contain enlarged vacuoles derived from the
      endosome/lysosome pathway, and astrocytes accumulate proteins involved in
      autophagy. Other cellular defects include astrogliosis and microgliosis. To
      distinguish the contributions of neurons and glia to spongiform degeneration in
      the Fig4 null mouse, we expressed Fig4 under the control of the neuron-specific
      enolase promoter and the astrocyte-specific glial fibrillary acidic protein
      promoter in transgenic mice. Neuronal expression of Fig4 was sufficient to rescue
      cellular and neurological phenotypes including spongiform degeneration, gliosis
      and juvenile lethality. In contrast, expression of Fig4 in astrocytes prevented
      accumulation of autophagy markers and microgliosis but did not prevent spongiform
      degeneration or lethality. To confirm the neuronal origin of spongiform
      degeneration, we generated a floxed allele of Fig4 and crossed it with mice
      expressing the Cre recombinase from the neuron-specific synapsin promoter. Mice
      with conditional inactivation of Fig4 in neurons developed spongiform
      degeneration and the full spectrum of neurological abnormalities. The data
      demonstrate that expression of Fig4 in neurons is necessary and sufficient to
      prevent spongiform degeneration. Therapy for patients with FIG4 deficiency will
      therefore require correction of the deficiency in neurons.

PMID- 22581780
TI  - Mutant superoxide dismutase 1 (SOD1), a cause of amyotrophic lateral sclerosis,
      disrupts the recruitment of SMN, the spinal muscular atrophy protein to nuclear
      Cajal bodies.
AB  - Spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) are among
      the most common motor neuron diseases to afflict the human population. A
      deficiency of the survival of motor neuron (SMN) protein causes SMA and is also
      reported to be an exacerbating factor in the development of ALS. However,
      pathways linking the two diseases have yet to be defined and it is not clear
      precisely how the pathology of ALS is aggravated by reduced SMN or whether mutant
      proteins underlying familial forms of ALS interfere with SMN-related biochemical
      pathways to exacerbate the neurodegenerative process. In this study, we show that
      mutant superoxide dismutase-1 (SOD1), a cause of familial ALS, profoundly alters
      the sub-cellular localization of the SMN protein, preventing the formation of
      nuclear 'gems' by disrupting the recruitment of the protein to Cajal bodies.
      Overexpressing the SMN protein in mutant SOD1 mice, a model of familial ALS,
      alleviates this phenomenon, most likely in a cell-autonomous manner, and
      significantly mitigates the loss of motor neurons in the spinal cord and in
      culture dishes. In the mice, the onset of the neuromuscular phenotype is delayed
      and motor function enhanced, suggestive of a therapeutic benefit for ALS patients
      treated with agents that augment the SMN protein. Nevertheless, this finding is
      tempered by an inability to prolong survival, a limitation most likely imposed by
      the inexorable denervation that characterizes ALS and eventually disrupts the
      neuromuscular synapses even in the presence of increased SMN.

PMID- 22581777
TI  - Identification of novel NRF2-regulated genes by ChIP-Seq: influence on retinoid X
      receptor alpha.
AB  - Cellular oxidative and electrophilic stress triggers a protective response in
      mammals regulated by NRF2 (nuclear factor (erythroid-derived) 2-like; NFE2L2)
      binding to deoxyribonucleic acid-regulatory sequences near stress-responsive
      genes. Studies using Nrf2-deficient mice suggest that hundreds of genes may be
      regulated by NRF2. To identify human NRF2-regulated genes, we conducted chromatin
      immunoprecipitation (ChIP)-sequencing experiments in lymphoid cells treated with
      the dietary isothiocyanate, sulforaphane (SFN) and carried out follow-up
      biological experiments on candidates. We found 242 high confidence, NRF2-bound
      genomic regions and 96% of these regions contained NRF2-regulatory sequence
      motifs. The majority of binding sites were near potential novel members of the
      NRF2 pathway. Validation of selected candidate genes using parallel ChIP
      techniques and in NRF2-silenced cell lines indicated that the expression of about
      two-thirds of the candidates are likely to be directly NRF2-dependent including
      retinoid X receptor alpha (RXRA). NRF2 regulation of RXRA has implications for
      response to retinoid treatments and adipogenesis. In mouse, 3T3-L1 cells' SFN
      treatment affected Rxra expression early in adipogenesis, and knockdown of Nrf2
      delayed Rxra expression, both leading to impaired adipogenesis.

PMID- 22581782
TI  - Lhx2-dependent specification of olfactory sensory neurons is required for
      successful integration of olfactory, vomeronasal, and GnRH neurons.
AB  - Inactivation of the LIM-homeodomain 2 gene (Lhx2) results in a severe defect in
      specification of olfactory sensory neurons (OSNs). However, the ramifications of
      lack of Lhx2-dependent OSN specification for formation of the primary olfactory
      pathway have not been addressed, since mutant mice die in utero. We have analyzed
      prenatal and postnatal consequences of conditionally inactivating Lhx2
      selectively in OSNs. A cell-autonomous effect is that OSN axons cannot innervate
      their target, the olfactory bulb. Moreover, the lack of Lhx2 in OSNs causes
      unpredicted, non-cell-autonomous phenotypes. First, the olfactory bulb shows
      pronounced hypoplasia in adults, and the data suggest that innervation by
      correctly specified OSNs is necessary for adult bulb size and organization.
      Second, absence of an olfactory nerve in the conditional mutant reveals that the
      vomeronasal nerve is dependent on olfactory nerve formation. Third, the lack of a
      proper vomeronasal nerve prevents migration of gonadotropin-releasing hormone
      (GnRH) cells the whole distance to their final positions in the hypothalamus
      during embryo development. As adults, the conditional mutants do not pass
      puberty, and these findings support the view of an exclusive nasal origin of GnRH
      neurons in the mouse. Thus, Lhx2 in OSNs is required for functional development
      of three separate systems.

PMID- 22581783
TI  - Microtubule and male sterility in a gene-cytoplasmic male sterile line of non
      heading Chinese cabbage.
AB  - BACKGROUND: Microtubules are the basic components of the cytoskeleton in
      eukaryotic cells and are made up of 13 parallel protofilaments, each composed of
      alpha- and beta-tubulin unit molecules aligned along the longitudinal axis of the
      microtubule. RESULTS: alpha-Tubulin gene TUBA2 from non-heading Chinese cabbage
      (Brassica campestris ssp. chinensis Makino) was expressed at the highest level in
      stamens and at lower levels in other organs. In addition, it was expressed at a
      much lower level in the cytoplasmic male sterile (CMS) line than in the
      maintainer line. Furthermore, at the microsporocyte stage of development in the
      CMS line the microtubule bundles were knitted together in random organisation,
      which differed significantly from the radiate microtubule bundles running
      circumferentially around the nucleus in the maintainer line. Also, large vacuoles
      appeared within the cytoplasm in the CMS line with no dyed microtubules.
      CONCLUSION: TUBA2 was very important to pollen development, which might be
      closely related to male sterility. Large vacuoles might replace the nuclei close
      to the cell walls and lead to a lack of microtubules when the cells abort.
      Abnormalities and defects in the organisation and composition of microtubules in
      the male sterile line highlighted the complex interaction between microtubules
      and cytoplasmic male sterility.

PMID- 22581784
TI  - The effects of Fabp7 and Fabp5 on postnatal hippocampal neurogenesis in the
      mouse.
AB  - New neurons are continually produced after birth from neural stem/progenitor
      cells (NSCs/NPCs) in the hippocampal dentate gyrus (DG). Recent studies have
      reported that fatty acid binding protein 7 (Fabp7/brain lipid binding protein
      (BLBP)) is required for the maintenance of embryonic NSCs/NPCs and have
      identified an association between the Fabp7 gene and behavioral paradigms that
      correlate with hippocampal functions. However, the specific roles of Fabps in
      postnatal neurogenesis remain unknown. Herein, we demonstrate the effects of
      Fabp7, and another Fabp, Fabp5, on postnatal neurogenesis. Fabp7 and Fabp5 were
      detected in the subgranular zone (SGZ) of the DG, and Fabp7+ cells were less
      differentiated than Fabp5+ cells. We analyzed the differentiation state of
      NSCs/NPCs in the SGZ of 4-week-old (4w) Fabp7 knockout (7KO), Fabp5 KO (5KO), and
      Fabp7/Fabp5 double KO (7/5KO) mice and found that the number of NSCs/NPCs was
      dramatically reduced compared with wild-type mice. Although the uptake of BrdU 1
      day after injection was decreased in all KO mice, the survival of BrdU+ cells 1
      month after injection was increased in the 7/5KO mice compared to other three
      genotypes. We also observed an enhancement of neuronal differentiation in all
      Fabp KO mice. In addition, the proliferation and survival of NSCs/NPCs differed
      along the anterior-posterior axis (A-P axis). A greater number of newborn cells
      in the posterior region became extinct, but this tendency was not apparent in the
      Fabps KO mice. These data suggest that Fabp7 and Fabp5 have differential roles
      for proliferation and survival of the NSCs/NPCs during postnatal DG neurogenesis.

PMID- 22581785
TI  - 14q13.1-21.1 deletion encompassing the HPE8 locus in an adolescent with
      intellectual disability and bilateral microphthalmia, but without
      holoprosencephaly.
AB  - Interstitial deletions involving 14q13.1q21.1 are rare. In the literature at
      least 10 cases involving this region have been described and all patients showed
      a phenotype within the holoprosencephaly (HPE) spectrum. Previous studies
      suggested the HPE8 region as a candidate locus for HPE at 14q13. We report an
      adolescent with a 14q13.1q21.1 deletion encompassing the HPE8 region associated
      with intellectual disability (ID), bilateral microphthalmia, and coloboma,
      without cerebral anomalies typical of HPE. Except for ocular defects (i.e.,
      microphthalmia, coloboma) consistent with HPE-type anomalies, the minor facial
      dysmorphia was not suggestive for HPE and the absence of cerebral anomalies
      should rule out this diagnosis. The deletion of the potential HPE candidate genes
      NPAS3, EAPP, SNX6, and TULIP1, raises doubts about their pathologic role in
      determining HPE. It is likely that deletions of HPE genes are not sufficient to
      cause HPE, and that multiple genetic, chromosomal, and environmental factors
      interact to determine the variable clinical expression of HPE. This is the first
      case of a 14q deletion encompassing the HPE8 locus with the only features
      consistent with HPE-type anomalies affecting the ocular system (i.e.,
      microphthalmia, coloboma), and without cerebral anomalies specific for HPE. The
      inclusion of potential HPE candidate genes in the deletion raises the question
      whether this patient is affected by a less severe form of HPE (HPE microform), or
      whether he has a new ID/MCA deletion syndrome.

PMID- 22581786
TI  - Device closure of paravalvular defects following transcatheter aortic valve
      replacement with the Edwards Sapien valve.
AB  - Paravalvular aortic insufficiency (AI) is observed in the majority of patients
      undergoing transcatheter aortic valve replacement (TAVR). While paravalvular AI
      is most commonly modest following TAVR, moderate or severe AI was seen in 10.5%
      and 6.8% of the PARTNER inoperable and high-risk cohorts at 1 year and has been
      reportedly associated with dyspnea and diminished survival. We report two cases
      of transcatheter heart valve (THV) associated paravalvular defects closed using
      catheter delivered devices. Both patients derived hemodynamic and symptomatic
      improvement from device closure. Additional research is warranted to define the
      adverse consequences of THV associated AI, indications for treatment, and risks
      associated with device closure of these defects.

PMID- 22581787
TI  - MR spectroscopic imaging and diffusion-weighted imaging of prostate cancer with
      Gleason scores.
AB  - PURPOSE: To investigate functional changes in prostate cancer patients with three
      pathologically proven different Gleason scores (GS) (3+3, 3+4, and 4+3) using
      magnetic resonance spectroscopic imaging (MRSI) and diffusion-weighted imaging
      (DWI). MATERIALS AND METHODS: In this study MRSI and DWI data were acquired in 41
      prostate cancer patients using a 1.5T MRI scanner with a body matrix combined
      with an endorectal coil. The metabolite ratios of (Cho+Cr)/Cit were calculated
      from the peak integrals of total choline (Cho), creatine (Cr), and citrate (Cit)
      in MRSI. Apparent diffusion coefficient (ADC) values were derived from DWI for
      three groups of Gleason scores. The sensitivity and specificity of MRSI and DWI
      in patients were calculated using receiver operating characteristic curve (ROC)
      analysis. RESULTS: The mean and standard deviation of (Cho+Cr)/Cit ratios of GS
      3+3, GS 3+4, and GS 4+3 were: 0.44 +/- 0.02, 0.56 +/- 0.06, and 0.88 +/- 0.11,
      respectively. For the DWI, the mean and standard deviation of ADC values in GS
      3+3, GS 3+4, and GS 4+3 were: 1.13 +/- 0.11, 0.97 +/- 0.10, and 0.83 +/- 0.08
      mm(2) /sec, respectively. Statistical significances were observed between the GS
      and metabolite ratio as well as ADC values and GS. CONCLUSION: Combined MRSI and
      DWI helps identify the presence and the proportion of aggressive cancer (ie,
      Gleason grade 4) that might not be apparent on biopsy sampling. This information
      can guide subsequent rebiopsy management, especially for active surveillance
      programs.

PMID- 22581788
TI  - The expression of LytM is down-regulated by RNAIII in Staphylococcus aureus.
AB  - LytM is one kind of autolysin expressed in Staphylococcus aureus. It can
      hydrolyze peptide bond of pentaglycine, which is the component of cell wall.
      Until now, the regulation on the expression of LytM is still unclear. Here, we
      found that the level of LytM in the RNAIII mutant was increased. RNAIII is an
      important small regulatory RNA in S. aureus. Our further investigation revealed
      that RNAIII can interact with the 5'UTR of lytM mRNA and block the ribosome
      binding sites [RBS]. So our results identified that LytM was the new target of
      RNAIII.

PMID- 22581789
TI  - Evidence of higher complexes between cucurbit[7]uril and cationic surfactants.
AB  - The host-guest assembly of CB7 with a series of alkyl(trimethyl)ammonium
      (C(n)TA(+)) surfactants of different chain lengths (n=6-18) has been studied. The
      complexation behaviour was investigated by NMR spectroscopy, isothermal titration
      calorimetry and kinetics measurements. The combined results of these techniques
      provided evidence for the formation of 1:1 inclusion and 2:1 external complexes
      in the cases of C(n)TA(+) with n=12-18. The binding constants for the 1:1
      complexes are independent of the alkyl chain length of the surfactant, whereas a
      relationship between K(2:1) and the chain length of the surfactant was found for
      the 2:1 complexes.

PMID- 22581790
TI  - Effect of IL12A and IL12B polymorphisms on the risk of Chlamydia trachomatis
      induced tubal factor infertility and disease severity.
AB  - BACKGROUND: Interleukin-12 (IL-12) and related cytokines induce activation and
      differentiation of T cells. Our aim was to investigate the associations between
      genetic differences in IL-12-family cytokines and the pathogenesis of chlamydial
      disease. METHODS: The final study population consisted of 100 women with
      Chlamydia trachomatis-induced tubal factor infertility (TFI) and 125 pregnant
      women as controls. Three single nucleotide polymorphisms (SNPs) of IL12A and
      seven SNPs of IL12B genes were determined from isolated DNA using the Sequenom
      system with matrix-assisted laser desorption/ionization time-of-flight (MALDI
      TOF) mass spectrometry. RESULTS: We found that the IL12B SNP rs3212227 was
      associated with both susceptibility and severity of TFI. The minor allele C was
      rare and only one CC homozygote was found among the controls. AC heterozygotes
      were more common among TFI cases than among controls (P = 0.009) and were
      associated with increased risk of TFI [odds ratios (OR) = 2.44, 95% confidence
      intervals (CI) = 1.23-4.87]. Carrying the minor allele C was also associated with
      disease severity (P for trend = 0.008) and moderate (OR = 2.51, 95% CI = 1.06
      5.95) and severe tubal damage (OR = 2.73, 95% CI = 1.15-6.52). CONCLUSIONS: The
      results suggest that variation in the IL12B gene partly explains inter-individual
      differences in disease susceptibility and severity.

PMID- 22581791
TI  - Pneumatocoele in a neonate with perinatal tuberculosis.

PMID- 22581792
TI  - Drugs used for comfort care after withdrawal of intensive treatment in tertiary
      neonatal units in the UK.

PMID- 22581793
TI  - Strategies to increase influenza vaccination rates: outcomes of a nationwide
      cross-sectional survey of UK general practice.
AB  - OBJECTIVE: To identify practice strategies associated with higher flu vaccination
      rates in primary care. DESIGN: Logistic regression analysis of data from a cross
      sectional online questionnaire. SETTING: 795 general practices across England.
      PARTICIPANTS: 569 practice managers, 335 nursing staff and 107 general
      practitioners. PRIMARY OUTCOME MEASURES: Flu vaccination rates achieved by each
      practice in different groups of at-risk patients. RESULTS: 7 independent factors
      associated with higher vaccine uptake were identified. Having a lead staff member
      for planning the flu campaign and producing a written report of practice
      performance predicted an 8% higher vaccination rate for at-risk patients aged <65
      years (OR 1.37, 95% CI 1.10 to 1.71). These strategies, plus sending a personal
      invitation to all eligible patients and only stopping vaccination when Quality
      and Outcomes Framework targets are reached, predicted a 7% higher vaccination
      rate (OR 1.45, 95% CI 1.10 to 1.92) in patients aged >=65 years. Using a lead
      member of staff for identifying eligible patients, with either a modified
      manufacturer's or in-house search programme for interrogating the practice IT
      system, independently predicted a 4% higher vaccination rate in patients aged
      >=65 years (OR 1.22, 95% CI 1.06 to 1.41/OR 1.20, 95% CI 1.03 to 1.40). The
      provision of flu vaccine by midwives was associated with a 4% higher vaccination
      rate in pregnant women (OR 1.19, 95% CI 1.02 to 1.40). CONCLUSIONS: Clear
      leadership, effective communication about performance and methods used to
      identify and contact eligible patients were independently associated with
      significantly higher rates of flu vaccination. Financial targets appear to
      incentivise practices to work harder to maximise seasonal influenza vaccine
      uptake. The strategies identified here could help primary care providers to
      substantially increase their seasonal flu vaccination rates towards or even above
      the Chief Medical Officer's targets.

PMID- 22581794
TI  - Public health concerns for anti-obesity medicines imported for personal use
      through the internet: a cross-sectional study.
AB  - OBJECTIVE: To explore the circulation of anti-obesity medicines via the internet
      and their quality. DESIGN: Cross-sectional study. SETTING: Internet pharmacies
      and pharmaceutical suppliers accessible from Japan. PARTICIPANTS: Anti-obesity
      medicines were purchased using relevant keywords on Japanese Google search
      engine. Blogs and advertisement-only sites were excluded. PRIMARY AND SECONDARY
      OUTCOME MEASURES: The authenticity of the samples was investigated in
      collaboration with the manufacturers of the samples and medicine regulatory
      authorities. Quality of the samples was assessed by pharmacopoeial analyses using
      high-performance liquid chromatography. RESULTS: 82 samples were purchased from
      36 internet sites. Approximately half of the sites did not mention a physical
      address, and 45% of the samples did not contain a package insert. A variety of
      custom declarations were made for the shipments of the samples: personal health
      items, supplement, medicines, general merchandise, tea and others. Among 82
      samples, 52 samples were analysed to check their pharmacopoeial quality.
      Authenticity responses were received from only five of 20 manufacturing
      companies. According to the pharmacopoeial analyses and authenticity
      investigation, three of the samples were identified as counterfeits and did not
      contain any active ingredients. Two of these samples were confirmed as
      counterfeits by the manufacturer of the authentic products. The manufacturer of
      the other sample did not respond to our request for an authenticity check even
      after several communication attempts. These counterfeit cases have been reported
      at the rapid alert system of Western Pacific Region of the WHO. CONCLUSIONS: Many
      counterfeit and unapproved anti-obesity medicines may be easily bypassing
      regulatory checks during shipping and are widely circulated through the internet.
      Regulatory authorities should take measures to prevent these medicines from
      entering countries to safeguard their citizens.

PMID- 22581795
TI  - The relationship between walking speed and changes in cardiovascular risk factors
      during a 12-day walking tour to Santiago de Compostela: a cohort study.
AB  - OBJECTIVES: Physical exercise has beneficial effects on cardiovascular risk
      factors. Knowledge about the effect of exercise intensity, specifically walking
      speed, on cardiovascular risk factors is limited. We report the relationship
      between walking speed and changes in cardiovascular risk factors in participants
      of a 12-day walking tour to Santiago de Compostela. DESIGN: Prospective cohort
      study. SETTING: Single-centre study with healthy middle-aged volunteers.
      PARTICIPANTS: Healthy middle-aged men (n=15) and women (n=14). Subjects using
      lipid-lowering medication were excluded. INTERVENTION: Participants walked 281+/
      10 km of the classical route to Santiago de Compostela in 12 days in 2009.
      PRIMARY AND SECONDARY OUTCOME MEASURES: Walking speed was recorded and blood
      pressure, weight, waist circumference, lipids and glucose were measured every
      other day. Changes in risk factors were compared between gender-pooled groups
      with faster and slower walking speed. Second, the relationship between walking
      speed and changes in risk factors was quantified using a linear mixed effects
      model. RESULTS: In the faster walking speed (4.6+/-0.2 km/h) group, high-density
      lipoprotein cholesterol (HDL-c) increased more than in the slower walking speed
      (4.1+/-0.2 km/h) group (difference in change between groups: 0.20; 95% CI -0.02
      to 0.42 mmol/l), while low-density lipoprotein cholesterol (LDL-c) and total
      cholesterol decreased more in the slower walking speed group (differences in
      changes between groups: LDL-c: -0.50; 95% CI -0.88 to -0.12 mmol/l and total
      cholesterol: -0.75; 95% CI -1.19 to -0.31 mmol/l). A 1 km/h higher walking speed
      was related to an increase in HDL-c (0.24; 95% CI 0.12 to 0.30 mmol/l), LDL-c
      (0.18; 95% CI -0.16 to 0.42 mmol/l) and total cholesterol (0.36; 95% CI 0.12 to
      0.60 mmol/l), adjusted for age, gender, smoking, body mass index and heart rate,
      during the whole walking tour. CONCLUSIONS: Walking the same distance faster
      improves HDL-c more, while LDL-c and total cholesterol decrease more with lower
      walking speed independent of changes in body weight in healthy middle-aged
      subjects.

PMID- 22581796
TI  - Antidopaminergic drugs and acute pancreatitis: a population-based study.
AB  - OBJECTIVES: To evaluate the suggested association between antidopaminergic drugs
      and acute pancreatitis. DESIGN: A large population-based nested case-control
      study. SETTING: Swedish nationwide study from 2006 to 2008. PARTICIPANTS: The
      Patient Register was used to identify 6161 cases of acute pancreatitis. The 61
      637 control subjects were randomly selected from the Register of the Total
      Population by frequency-based density sampling, matched for age, sex and calendar
      year. EXPOSURE: Exposure data were extracted from the Prescribed Drug Register.
      Antidopaminergic drugs were grouped into antiemetic/anxiolytic and other
      antipsychotics. Current use of antidopaminergic drugs was defined as filling a
      prescription 1-114 days before index date, while previous use was 115 days to 3.5
      years before index date. MAIN OUTCOME MEASURES: Cases were defined as being
      diagnosed as having acute pancreatitis. ORs and 95% CIs were calculated using
      unconditional logistic regression. RESULTS: The unadjusted OR indicated an
      increased risk of acute pancreatitis among current users of
      antiemetic/anxiolytics (OR 1.9, 95% CI 1.4 to 2.6), but not in the multivariable
      model adjusting for alcohol-related comorbidity, chronic obstructive lung
      disease, ischaemic heart disease, obesity, diabetes, opioid use, gallstone
      disease, educational level, marital status and number of concomitant medications
      (OR 0.9, 95% CI 0.6 to 1.2). Similarly, among current users of other
      antipsychotics, the unadjusted OR was 1.4 (95% CI 1.1 to 1.6), while the adjusted
      OR was 0.8 (95% CI 0.6 to 0.9). Results regarding previous use of
      antidopaminergic drugs followed a similar risk pattern as for current use.
      CONCLUSIONS: The lack of association between antidopaminergic drugs and acute
      pancreatitis after adjustment for confounding factors in this study suggests that
      the previously reported positive associations might be explained by confounding.

PMID- 22581797
TI  - Impact of obesity, overweight and underweight on life expectancy and lifetime
      medical expenditures: the Ohsaki Cohort Study.
AB  - OBJECTIVES: People who are obese have higher demands for medical care than those
      of the normal weight people. However, in view of their shorter life expectancy,
      it is unclear whether obese people have higher lifetime medical expenditure. We
      examined the association between body mass index, life expectancy and lifetime
      medical expenditure. DESIGN: Prospective cohort study using individual data from
      the Ohsaki Cohort Study. SETTING: Miyagi Prefecture, northeastern Japan.
      PARTICIPANTS: The 41 965 participants aged 40-79 years. PRIMARY AND SECONDARY
      OUTCOME MEASURES: The life expectancy and lifetime medical expenditure aged from
      40 years. RESULTS: In spite of their shorter life expectancy, obese participants
      might require higher medical expenditure than normal weight participants. In men
      aged 40 years, multiadjusted life expectancy for those who were obese
      participants was 41.4 years (95% CI 38.28 to 44.70), which was 1.7 years non
      significantly shorter than that for normal weight participants (p=0.3184).
      Multiadjusted lifetime medical expenditure for obese participants was L112 858.9
      (94 954.1-131 840.9), being 14.7% non-significantly higher than that for normal
      weight participants (p=0.1141). In women aged 40 years, multiadjusted life
      expectancy for those who were obese participants was 49.2 years (46.14-52.59),
      which was 3.1 years non-significantly shorter than for normal weight participants
      (p=0.0724), and multiadjusted lifetime medical expenditure was L137 765.9 (123
      672.9-152 970.2), being 21.6% significantly higher (p=0.0005). CONCLUSIONS:
      According to the point estimate, lifetime medical expenditure might appear to be
      higher for obese participants, despite their short life expectancy. With weight
      control, more people would enjoy their longevity with lower demands for medical
      care.

PMID- 22581798
TI  - Dopamine acts through Cryptochrome to promote acute arousal in Drosophila.
AB  - The fruit fly, Drosophila melanogaster, is generally diurnal, but a few mutant
      strains, such as the circadian clock mutant Clk(Jrk), have been described as
      nocturnal. We report here that increased nighttime activity of Clk mutants is
      mediated by high levels of the circadian photoreceptor CRYPTOCHROME (CRY) in
      large ventral lateral neurons (l-LN(v)s). We found that CRY expression is also
      required for nighttime activity in mutants that have high dopamine signaling. In
      fact, dopamine signaling is elevated in Clk(Jrk) mutants and acts through CRY to
      promote the nocturnal activity of this mutant. Notably, dopamine and CRY are
      required for acute arousal upon sensory stimulation. Because dopamine signaling
      and CRY levels are typically high at night, this may explain why a chronic
      increase in levels of these molecules produces sustained nighttime activity. We
      propose that CRY has a distinct role in acute responses to sensory stimuli: (1)
      circadian responses to light, as previously reported, and (2) noncircadian
      effects on arousal, as shown here.

PMID- 22581799
TI  - Changes in descending motor pathway connectivity after corticospinal tract lesion
      in macaque monkey.
AB  - Damage to the corticospinal tract is a leading cause of motor disability, for
      example in stroke or spinal cord injury. Some function usually recovers, but
      whether plasticity of undamaged ipsilaterally descending corticospinal axons
      and/or brainstem pathways such as the reticulospinal tract contributes to
      recovery is unknown. Here, we examined the connectivity in these pathways to
      motor neurons after recovery from corticospinal lesions. Extensive unilateral
      lesions of the medullary corticospinal fibres in the pyramidal tract were made in
      three adult macaque monkeys. After an initial contralateral flaccid paralysis,
      motor function rapidly recovered, after which all animals were capable of
      climbing and supporting their weight by gripping the cage bars with the
      contralesional hand. In one animal where experimental testing was carried out,
      there was (as expected) no recovery of fine independent finger movements. Around
      6 months post-lesion, intracellular recordings were made from 167 motor neurons
      innervating hand and forearm muscles. Synaptic responses evoked by stimulating
      the unlesioned ipsilateral pyramidal tract and the medial longitudinal fasciculus
      were recorded and compared with control responses in 207 motor neurons from six
      unlesioned animals. Input from the ipsilateral pyramidal tract was rare and weak
      in both lesioned and control animals, suggesting a limited role for this pathway
      in functional recovery. In contrast, mono- and disynaptic excitatory post
      synaptic potentials elicited from the medial longitudinal fasciculus
      significantly increased in average size after recovery, but only in motor neurons
      innervating forearm flexor and intrinsic hand muscles, not in forearm extensor
      motor neurons. We conclude that reticulospinal systems sub-serve some of the
      functional recovery after corticospinal lesions. The imbalanced strengthening of
      connections to flexor, but not extensor, motor neurons mirrors the extensor
      weakness and flexor spasm which in neurological experience is a common limitation
      to recovery in stroke survivors.

PMID- 22581801
TI  - Genetic variants in TEX15 gene conferred susceptibility to spermatogenic failure
      in the Chinese Han population.
AB  - This study aimed to analyze the distribution of single-nucleotide polymorphisms
      (SNPs) of testis-expressed 15 (TEX15) gene in the Chinese Han infertile men and
      fertile men. This case-control study comprised 309 infertile men with
      nonobstructive azoospermia (NOA, n = 199) or severe oligozoospermia (SO, n = 110)
      and 377 fertile controls. Six SNPs were genotyped by Sequenom iplex technology.
      The results showed that the variants rs323346 and rs323347 contributed to the
      increasing risk of SO (P = .041, odds ratio [OR] = 1.635, 95% confidence interval
      [CI] = 1.018-2.628 and P = .046, OR = 1.616, 95% CI = 1.006-2.597). The haplotype
      AT of the SNPs rs323347 and rs323346 could reduce risk in the patients with SO (P
      = .040, OR = 0.616, and 95% CI = 0.383-0.990). The haplotype GC of the variants
      rs323347 and rs323346 conferred a significantly increased risk of SO (P = .040,
      OR = 1.624, 95% CI = 1.010-2.610). Thus, the polymorphisms rs323346 and rs323347
      of the TEX15 gene could be considered the genetic risk factors for spermatogenic
      failure in the Chinese Han population.

PMID- 22581800
TI  - BRAFV600E remodels the melanocyte transcriptome and induces BANCR to regulate
      melanoma cell migration.
AB  - Aberrations of protein-coding genes are a focus of cancer genomics; however, the
      impact of oncogenes on expression of the ~50% of transcripts without protein
      coding potential, including long noncoding RNAs (lncRNAs), has been largely
      uncharacterized. Activating mutations in the BRAF oncogene are present in >70% of
      melanomas, 90% of which produce active mutant BRAF(V600E) protein. To define the
      impacts of oncogenic BRAF on the melanocyte transcriptome, massively parallel
      cDNA sequencing (RNA-seq) was performed on genetically matched normal human
      melanocytes with and without BRAF(V600E) expression. To enhance potential disease
      relevance by verifying expression of altered genes in BRAF-driven cancer tissue,
      parallel RNA-seq was also undertaken of two BRAF(V600E)-mutant human melanomas.
      BRAF(V600E) regulated expression of 1027 protein-coding transcripts and 39
      annotated lncRNAs, as well as 70 unannotated, potentially novel, intergenic
      transcripts. These transcripts display both tissue-specific and multi-tissue
      expression profiles and harbor distinctive regulatory chromatin marks and
      transcription factor binding sites indicative of active transcription. Coding
      potential analysis of the 70 unannotated transcripts suggested that most may
      represent newly identified lncRNAs. BRAF-regulated lncRNA 1 (BANCR) was
      identified as a recurrently overexpressed, previously unannotated 693-bp
      transcript on chromosome 9 with a potential functional role in melanoma cell
      migration. BANCR knockdown reduced melanoma cell migration, and this could be
      rescued by the chemokine CXCL11. Combining RNA-seq of oncogene-expressing normal
      cells with RNA-seq of their corresponding human cancers may represent a useful
      approach to discover new oncogene-regulated RNA transcripts of potential clinical
      relevance in cancer.

PMID- 22581802
TI  - Nature of light: spectroscopic techniques in obstetrics and gynecology
      applications.
AB  - In recent years, advances in spectroscopic techniques led to an increase in their
      medical applications. In medical sciences, emphasis is increasingly placed on
      instrumental techniques and accurate, quantitative measurements. It is especially
      apparent in diagnosis, where imaging techniques and laboratory results have
      became invaluable and compulsory. Breakthroughs in biochemistry made it possible
      to characterize physiological processes and living organisms at the molecular
      level. This led to a proliferation of new methods such as DNA tests and the use
      of biomarkers in daily clinical practice. Characterization of molecular structure
      and determination of the composition of a mixture are the fields of analytical
      chemistry and analytical biochemistry.

PMID- 22581803
TI  - Elevated prevalence of 35-44 FMR1 trinucleotide repeats in women with diminished
      ovarian reserve.
AB  - INTRODUCTION: Fragile X premutations are associated with primary ovarian
      insufficiency when the patient presents with amenorrhea, but the fragile X mental
      retardation 1 (FMR1) CGG repeat count among cycling women with low ovarian
      reserve (diminished ovarian reserve [DOR]) is not yet established. PATIENTS AND
      METHODS: Sixty-two infertile DOR patients were recruited from 4 US private and
      academic fertility centers. RESULTS: The prevalence of 35-44 FMR1 CGG repeats was
      14.5%. Compared with the general female population estimate from the literature,
      infertile women with DOR were more likely to have 35-44 FMR1 CGG repeats (14.5%
      and 3.9%, respectively, P = .0003). Similar findings were noted by 5-repeat
      bandwidth: 35-39 CGG repeats (9.7% DOR vs 3.2% comparison, P = .012) or 40-44 CGG
      repeats (4.8% DOR vs 0.7% comparison, P = .024). CONCLUSIONS: These data suggest
      that CGG repeats of 35-44 may be markedly overrepresented in women with DOR,
      whereas the current FMR1 reference range indicates that there is no clinical
      phenotype with <45 CGG repeats.

PMID- 22581804
TI  - Psychological experience of parents of children with type 1 diabetes: a
      systematic mixed-studies review.
AB  - PURPOSE: The purpose of this review is to describe the prevalence of
      psychological distress in parents of children with type 1 diabetes (T1DM), the
      relationship between parental psychological distress and health outcomes, and
      parents' psychological experience of having a child with T1DM. Clinical and
      research implications are presented. METHOD: A systematic mixed-studies review
      was undertaken to review the quantitative and qualitative research on the
      parental experience of having a child with T1DM. A total of 34 articles met the
      inclusion criteria and were included in the review. RESULTS: The prevalence of
      parental psychological distress across all studies ranged from 10% to 74%, with
      an average of 33.5% of parents reporting distress at diagnosis and 19% of parents
      reporting distress 1 to 4 years after diagnosis. Parental psychological distress
      in parents of children with T1DM, regardless of how it was defined, was
      associated with higher child self-report of stress and depressive symptoms, more
      problematic child behavior, and lower child self-report of quality of life.
      Parental psychological distress also had negative effects on diabetes management.
      Themes of the qualitative synthesis indicated that parents perceived T1DM as a
      difficult diagnosis that contributed to significant family disruption. Adjustment
      occurred over time; however, ongoing stress was experienced. CONCLUSIONS:
      Screening for psychological distress in parents of children with T1DM is
      indicated, and preventive interventions are needed.

PMID- 22581806
TI  - Systemic local anaesthetic toxicity from continuous thoracic paravertebral block.
AB  - Continuous paravertebral block is commonly used for post-thoracotomy analgesia
      and compares favourably with other systemic and regional methods with regard to
      safety and efficacy. No major complications of continuous paravertebral block for
      post-thoracotomy analgesia have been reported previously. We report here a case
      of systemic local anaesthetic toxicity from continuous paravertebral block
      administration after thoracotomy and lobectomy leading to seizure, aspiration,
      and ultimately, death. Potential contributing factors in this case included small
      patient size, concomitant antifungal therapy, extensive surgical disruption of
      the pleurae, and inappropriate paravertebral bolus administration. Postoperative
      delirium was a diagnostic confounder. We discuss the potential causes and means
      of avoiding similar complications in the future.

PMID- 22581807
TI  - Long-term and spatial memory effects of selective beta1-antagonists after
      transient focal ischaemia in rats.
AB  - BACKGROUND: Although various reports have shown that beta-antagonists provide
      neuroprotective effects after cerebral ischaemia, their effect on spatial memory
      after transient focal ischaemia is not known. We investigated the treatment of
      beta1-antagonists on neurological outcome spatial memory for 1 month after focal
      cerebral ischaemia in rats. METHODS: Male rats randomly received an i.v. infusion
      of saline 0.5 ml h(-1), esmolol 200 MUg kg(-1) min(-1), or landiolol 50 MUg kg(
      1) min(-1). Infusion was initiated 30 min before middle cerebral artery occlusion
      and continued for 24 h. The infarct areas in the hippocampus and striatum were
      measured after the final retention trial and neurological examinations. RESULTS:
      Neurological deficit scores in the landiolol- and esmolol-treated rats were
      significantly lower than in the control rats at 1, 4, 7, and 11 days after
      ischaemia (P<0.05). Using the Morris water maze to assess spatial memory, we
      found that escape latency and swimming path length to the platform were
      significantly shorter in the landiolol-treated rats, compared with the saline
      treated rats at 4 and 11 days after ischaemia (P<0.05). The mean (SD) infarct
      area was 19.1 (8.0)% in the striatum and 18.6 (10.0)% in the hippocampus of the
      landiolol-treated rats, and 16.8 (14.0)% and 16.8 (15.0)% in the striatum and
      hippocampus, respectively, of esmolol-treated rats. This was significantly less
      than in control rats [striatum 31.7 (14.0)% and hippocampus 29.8 (13.0)%,
      P<0.05]. CONCLUSIONS: The current study indicates that although esmolol and
      landiolol provided long-term neuroprotection in terms of histological outcome,
      they had no effect on neurological outcome and spatial memory retention.

PMID- 22581805
TI  - Detailed O-glycomics of the Muc2 mucin from colon of wild-type, core 1- and core
      3-transferase-deficient mice highlights differences compared with human MUC2.
AB  - The heavily O-glycosylated mucin MUC2 constitutes the major protein in the
      mucosal layer that acts as a physical barrier protecting the epithelial layer in
      the colon. In this study, Muc2 was purified from mucosal scrapings from the colon
      of wild-type (WT) mice, core 3 transferase knockout (C3Gnt(-/-)) mice and
      intestinal epithelial cell-specific core 1 knockout (IEC C1Galt1(-/-)) mice. The
      Muc2 O-glycans were released by reductive beta-elimination and analyzed with
      liquid chromatography-mass spectrometry in the negative-ion mode. Muc2 from the
      distal colon of WT and C3Gnt(-/-) knockout mice carried a mixture of core 1- or
      core 2-type glycans, whereas Muc2 from IEC C1Galt1(-/-) mice carried highly
      sialylated core 3- and core 4-type glycans. A large portion of NeuAc in all mouse
      models was positioned on disialylated N-acetyllactosamine units, an epitope not
      reported on human colonic MUC2. Mass spectra and proton NMR spectroscopy revealed
      an abundant NeuAc linked to internally positioned N-acetylglucosamine on colonic
      murine Muc2, which also differs markedly from human MUC2. Our results highlight
      that murine colonic Muc2 O-glycosylation is substantially different from human
      MUC2, which could be one explanation for the different commensal microbiota of
      these two species.

PMID- 22581808
TI  - Non-technical skills of anaesthetic assistants in the perioperative period: a
      literature review.
AB  - Non-technical skills (NTS), which include communication, teamwork, leadership,
      decision-making, and situation awareness, are important in the maintenance of
      patient safety. NTS frameworks have been developed for anaesthetists, surgeons,
      and scrub practitioners. Most studies of NTS in operating theatres to date have
      focused on anaesthetists and surgeons. We have attempted to identify the NTS used
      by anaesthetic assistants in the perioperative period. An electronic search of
      the NHS e-library, PubMed, BioMed Central, ScienceDirect, and Scopus databases
      was performed in December 2010. The abstracts of the papers identified were
      checked for relevance and the article examined. Out of 308 papers initially
      identified, there were only three papers describing the use of NTS by anaesthetic
      assistants. Communication and situation awareness were described in three papers,
      teamwork and decision-making in two, and leadership in one. This search did not
      reveal any comprehensive description of the NTS required by anaesthetic
      assistants. The benefits of developing an NTS taxonomy for anaesthetic assistants
      are discussed.

PMID- 22581809
TI  - Database of the radioactivity of norm used as industrial raw materials.
AB  - Most ores used as industrial raw materials are imported mainly because Japan has
      poor natural resources. The activity concentrations in these materials should be
      investigated to evaluate the radiation exposure of workers. In this study,
      imported industrial raw materials were collected, and the activity concentrations
      in these resources were measured by using inductively coupled plasma mass
      spectrometry and gamma ray spectrometry. Furthermore,  a database of activity
      concentrations of NORMs was developed by referring to the measured results as
      well as referring to the literature, and a database on the web was published. The
      purpose of the database is to relieve anxieties among the general public and to
      provide extensive data regarding NORM for researchers and regulators. The
      database provides more than 900 activity concentrations in worldwide NORMs at no
      fee. (NORM database; http://www.nirs.go.jp/db/anzendb/NORMDB/ENG/index.php).

PMID- 22581810
TI  - Evaluation of novel acute urinary rat kidney toxicity biomarker for subacute
      toxicity studies in preclinical trials.
AB  - Novel urinary protein biomarkers for the detection of acute renal damage,
      recently accepted by the U.S. Food and Drug Administration, European Medicines
      Agency, and Pharmaceuticals and Medical Devices Agency (Japan), now have to be
      validated in practice. Limited data regarding the performance of these acute
      markers after subacute or subchronic treatment are publicly available. To
      increase the area of applicability of these markers, it is important to evaluate
      the ability to detect them after 28 days of treatment or even longer. Wistar rats
      were treated with three doses of cisplatin, vancomycin, or puromycin to induce
      renal damage. Twelve candidate proteins were measured by Luminex xMAP-based
      WideScreen assays, MesoScale Discovery-based MULTI-SPOT technology, or RENA-strip
      dipstick assay after 28 days. Treatment with all three model compounds resulted
      in a dose-dependent increase in urinary biomarkers, specific for the observed
      areas within the nephron, determined histopathologically. The most promising
      biomarkers in this study were NGAL, Kim-1, osteopontin, clusterin, RPA-1, and
      GSTYb1, detected by multiplexing technologies. The RENA-strip dipstick assay
      delivered good diagnostic results for vancomycin-treated but not for cisplatin-
      or puromycin-treated rats. Taken together, the data show that these new
      biomarkers are robust and measurable for longer term studies to predict different
      types of kidney toxicities.

PMID- 22581811
TI  - Tissue Kim-1 and urinary clusterin as early indicators of cisplatin-induced acute
      kidney injury in rats.
AB  - The kidney is one of the main targets of drug toxicity, and early detection of
      renal damage is critical in preclinical drug development. A model of cisplatin
      induced nephrotoxicity in male Sprague Dawley rats treated for 1, 3, 5, 7, or 14
      days at 1 mg/kg/day was used to monitor the spatial and temporal expression of
      various indicators of kidney toxicity during the progression of acute kidney
      injury (AKI). As early as 1 day after cisplatin treatment, positive kidney injury
      molecule-1 (Kim-1) immunostaining, observed in the outer medulla of the kidney,
      and changes in urinary clusterin indicated the onset of proximal tubular injury
      in the absence of functional effects. After 3 days of treatment, Kim-1 protein
      levels in urine increased more than 20-fold concomitant with a positive clusterin
      immunostaining and an increase in urinary osteopontin. Tubular basophilia was
      also noted, while serum creatinine and blood urea nitrogen levels were elevated
      only after 5 days, together with tubular degeneration. In conclusion, tissue Kim
      1 and urinary clusterin were the most sensitive biomarkers for detection of
      cisplatin-induced kidney damage. Thereafter, urinary Kim-1 and osteopontin, as
      well as clusterin immunostaining accurately correlated with the histopathological
      findings. When AKI is suspected in preclinical rat studies, Kim-1, clusterin, and
      osteopontin should be part of urinalysis and/or IHC can be performed.

PMID- 22581812
TI  - Smooth muscle adaptation and recovery of contractility after massive small bowel
      resection in rats.
AB  - Previous studies have suggested that massive small bowel resection (mSBR)
      compromises the normal intestinal processes of digestion and absorption, and
      requires an adaptive response to regain full function and reinstate coordinated
      contractile activity of the circular smooth muscle. This study was designed to
      investigate spontaneous contractile activity of circular smooth muscle using the
      mSBR rat model and to determine the functional role of M(2) and M(3) muscarinic
      acetylcholine receptors (mAChR) in this process. Male Sprague-Dawley rats
      underwent an 80% proximal SBR or sham operation. Markers of adaptation, including
      villus and microvillus height, were analyzed by hematoxylin and eosin staining
      and transmission electron microscopy. Contractility was measured by attaching the
      distal ileum strips to strain gauge transducers and exposing the tissue to
      varying doses of the cholinergic agonist carbachol. Protein expressions of M(2)-
      and M(3)-mAChR in intestinal smooth muscle (ISM) were detected by Western blot.
      Following mSBR, the ISM showed perturbed spontaneous rhythmic contraction,
      irregular amplitude and slow frequency by muscle strip test. However, by two
      weeks after mSBR, the contractile function of circular smooth muscle was found to
      have returned to normal levels. Protein expression of M(2)-mAChR was down
      regulated following mSBR but up-regulated during the adaptive process when
      contractile activity of circular smooth muscle was regained. These results
      indicate that smooth muscle contractility was spontaneously restored in rats
      following mSBR, and involved the acetylcholine receptors M(2) and M(3). Thus, the
      disrupted contractile response of smooth muscle in short bowel syndrome may be
      corrected by therapeutic intervention to restore the expressions of M(2)- and
      M(3)-mAChR to pre-mSBR levels.

PMID- 22581813
TI  - Effects of RNA interference-induced Smad3 gene silencing on pulmonary fibrosis
      caused by paraquat in mice.
AB  - Paraquat (PQ) poisoning induces many physiological and histological changes in
      the human body, but PQ-induced pulmonary fibrosis is most often associated with
      death. The signaling pathway associated with pulmonary fibrosis is reliant on
      transforming growth factor-beta 1 (tgf-beta(1)) activation of Smad3, as evidenced
      by Smad3-deficient mice being resistant to tgf-beta(1)-induced pulmonary
      fibrosis. Thus, we sought to determine whether targeted silencing of Smad3 gene
      expression could inhibit PQ-induced pulmonary fibrosis in mice. We developed an
      RNA interference (RNAi) method using short hairpin RNAs (shRNAs) targeting Smad3.
      The shRNA expression cassettes capable of effectively silencing Smad3 in L929
      mouse fibroblasts were transferred to an adenovirus vector and intratracheally
      administered into mouse lung. Treated mice presented with inhibited Smad3 mRNA
      and protein and were resistant to PQ-induced pulmonary fibrosis, as evidenced by
      suppressed expressions of procollagen type I mRNA and hydroxyproline amino acid.
      Thus, silencing of Smad3 appears to be a promising alternative strategy for the
      treatment of PQ-induced pulmonary fibrosis.

PMID- 22581814
TI  - Insulin-like growth factor and fibroblast growth factor expression profiles in
      growth-restricted fetal sheep pancreas.
AB  - Placental insufficiency results in intrauterine growth restriction (IUGR),
      impaired fetal insulin secretion and less fetal pancreatic beta-cell mass, partly
      due to lower beta-cell proliferation rates. Insulin-like growth factors (IGFs)
      and fibroblast growth factors (FGFs) regulate fetal beta-cell proliferation and
      pancreas development, along with transcription factors, such as pancreatic and
      duodenal homeobox 1 (PDX-1). We determined expression levels for these growth
      factors, their receptors and IGF binding proteins in ovine fetal pancreas and
      isolated islets. In the IUGR pancreas, relative mRNA expression levels of IGF-I,
      PDX-1, FGF7 and FGFR2IIIb were 64% (P < 0.01), 76% (P < 0.05), 76% (P < 0.05) and
      52% (P < 0.01) lower, respectively, compared with control fetuses. Conversely,
      insulin-like growth factor binding protein 2 (IGFBP-2) mRNA and protein
      concentrations were 2.25- and 1.2-fold greater (P < 0.05) in the IUGR pancreas
      compared with controls. In isolated islets from IUGR fetuses, IGF-II and IGFBP-2
      mRNA concentrations were 1.5- and 3.7-fold greater (P < 0.05), and insulin mRNA
      was 56% less (P < 0.05) than control islets. The growth factor expression
      profiles for IGF and FGF signaling pathways indicate that declines in beta-cell
      mass are due to decreased growth factor signals for both pancreatic progenitor
      epithelial cell and mature beta-cell replication.

PMID- 22581816
TI  - Assessing individual breast cancer risk within the U.K. National Health Service
      Breast Screening Program: a new paradigm for cancer prevention.
AB  - The aim of this study is to determine breast cancer risk at mammographic
      screening episodes and integrate standard risk factors with mammographic density
      and genetic data to assess changing the screening interval based on risk and
      offer women at high risk preventive strategies. We report our experience of
      assessing breast cancer risk within the U.K. National Health Service Breast
      Screening Program using results from the first 10,000 women entered into the
      "Predicting Risk Of breast Cancer At Screening" study. Of the first 28,849 women
      attending for screening at fifteen sites in Manchester 10,000 (35%) consented to
      study entry and completed the questionnaire. The median 10-year Tyrer-Cuzick
      breast cancer risk was 2.65% (interquartile range, 2.10-3.45). A total of 107
      women (1.07%) had 10-year risks 8% or higher (high breast cancer risk), with a
      further 8.20% having moderately increased risk (5%-8%). Mammographic density
      (percent dense area) was 60% or more in 8.3% of women. We collected saliva
      samples from 478 women for genetic analysis and will extend this to 18% of
      participants. At time of consent to the study, 95.0% of women indicated they
      wished to know their risk. Women with a 10-year risk of 8% or more or 5% to 8%
      and mammographic density of 60% or higher were invited to attend or be telephoned
      to receive risk counseling; 81.9% of those wishing to know their risk have
      received risk counseling and 85.7% of these were found to be eligible for a risk
      reducing intervention. These results confirm the feasibility of determining
      breast cancer risk and acting on the information in the context of population
      based mammographic screening.

PMID- 22581815
TI  - Dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced
      prostate carcinogenesis in CYP1A-humanized mice.
AB  - To develop a relevant mouse model for prostate cancer prevention research, we
      administered a dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine (PhIP), to CYP1A-humanized mice. In comparison with mouse Cyp1a2,
      human CYP1A2 preferentially activates PhIP to a proximate carcinogen. Following a
      single oral dose of PhIP (200 mg/kg body weight), we observed inflammation,
      atrophy of acini, low-grade prostatic intraepithelial neoplasia (PIN; after 20
      weeks), and high-grade PIN (HgPIN; after 30 to 50 weeks) in dorsolateral,
      ventral, and coagulating anterior prostate glands of these mice. These lesions
      were androgen receptor positive and featured the loss of expression of the basal
      cell marker p63 and the tumor suppressor PTEN. Similar to human prostate
      carcinogenesis, glutathione S-transferase P1 (GSTP1) expression was lost or
      partially lost in HgPIN. E-Cadherin expression was also lost in HgPIN. The
      expression of DNA methyltransferase 1 was elevated, possibly to enhance promoter
      hypermethylation for the silencing of GSTP1 and E-cadherin. Prostate
      carcinogenesis was promoted by a high-fat stress diet, resulting in HgPIN that
      developed earlier and in advanced lesions displayed features consistent with
      carcinoma in situ. This dietary carcinogen-induced prostate cancer model,
      recapitulating important features of early human prostate carcinogenesis,
      constitutes a new experimental system for prostate cancer research.

PMID- 22581817
TI  - Citicoline enhances neuroregenerative processes after experimental stroke in
      rats.
AB  - BACKGROUND AND PURPOSE: The neuroprotective potential of citicoline in acute
      ischemic stroke has been shown in many experimental studies and, although the
      exact mechanisms are still unknown, a clinical Phase III trial is currently
      underway. Our present study was designed to check whether citicoline also
      enhances neuroregeneration after experimental stroke. METHODS: Forty Wistar rats
      were subjected to photothrombotic stroke and treated either with daily injections
      of citicoline (100 mg/kg) or vehicle for 10 consecutive days starting 24 hours
      after ischemia induction. Sensorimotor tests were performed after an adequate
      training period at Days 1, 10, 21, and 28 after stroke. Then brains were removed
      and analyzed for infarct size, glial scar formation, neurogenesis, and ligand
      binding densities of excitatory and inhibitory neurotransmitter receptors.
      RESULTS: Animals treated with citicoline showed a significantly better
      neurological outcome at Days 10, 21, and 28 after ischemia, which could not be
      attributed to differences in infarct volumes or glial scar formation. However,
      neurogenesis in the dentate gyrus, subventricular zone, and peri-infarct area was
      significantly increased by citicoline. Furthermore, enhanced neurological outcome
      after citicoline treatment was associated with a shift toward excitation in the
      perilesional cortex. CONCLUSIONS: Our present data demonstrate that, apart from
      the well-known neuroprotective effects in acute ischemic stroke, citicoline also
      possesses a substantial neuroregenerative potential. Thanks to its multimodal
      effects, easy applicability, and history as a well-tolerated drug, promising
      possibilities of neurological treatment including chronic stroke open up.

PMID- 22581818
TI  - High-dose statins should only be used in atherosclerotic strokes.

PMID- 22581820
TI  - Distributional impact of brain microbleeds on global cognitive function in adults
      without neurological disorder.
AB  - BACKGROUND AND PURPOSE: Brain microbleeds (MBs) are considered to be associated
      with cognitive decline and can be pathologically and topographically classified
      as cerebral amyloid angiopathy-related (located in lobar regions) and
      hypertensive microangiopathy-related (located in deep regions). We examined
      whether different effects on global cognitive function might be seen with
      different distributions of MBs. METHODS: A total of 1279 adults without
      neurological disorders were studied prospectively. Subjects were divided into 4
      groups: without-MBs group; lobar group; deep group; and with in both areas
      (diffuse group). The Mini-Mental State Examination was administered to determine
      global cognitive functions, with scores<27 regarded as subnormal. RESULTS: MBs
      were detected in 98 subjects (8%): 36 subjects (3%) classified as lobar group, 48
      subjects (4%) as deep group, and 14 subjects (1%) as diffuse group. Subnormal
      scores were found in 76 subjects (5.9%), associated with age, education,
      hypertension, severe white matter hyperintensities, and distribution and number
      of MBs. In the final model of logistic regression analysis, the deep group (OR,
      2.79; 95% CI, 1.14-6.79) was associated with subnormal scores, whereas the lobar
      group (OR, 0.77; 95% CI, 0.17-3.44) was not. Trend for the diffuse group did not
      reach the level of significance (OR, 5.01; 95% CI, 0.88-28.41). These trends were
      also seen in analysis using another cut-off point for subnormal score. Scores for
      total Mini-Mental State Examination and attention and calculation were
      significantly lower in the deep group and the diffuse groups compared with the
      without-MBs group. CONCLUSIONS: This Japanese cross-sectional study demonstrated
      that MB-related global cognitive dysfunction seems to occur based on hypertensive
      pathogenesis rather than on cerebral amyloid angiopathy.

PMID- 22581819
TI  - Leukoaraiosis predicts parenchymal hematoma after mechanical thrombectomy in
      acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to determine whether
      leukoaraiosis (LA) predicts hemorrhagic transformation and poor outcome in
      patients with acute ischemic stroke treated by mechanical thrombectomy. METHODS:
      We retrospectively analyzed patients with anterior circulation stroke treated
      with Merci devices and identified LA in the deep white matter (DWM) and
      periventricular white matter on the preintervention MR images. We dichotomized
      patients into those with moderate or severe LA in the DWM versus those without.
      Hemorrhage rates and outcomes were evaluated between 2 groups. We analyzed the
      association of moderate or severe LA with hemorrhagic transformation and poor
      outcome. RESULTS: Twenty-six of 105 patients had moderate or severe LA in the
      DWM. Patients with moderate or severe LA in the DWM were older, had more severe
      neurological deficits and worse outcome, had higher rates of hemorrhagic
      transformation and parenchymal hematoma, but had equivalent rates of hemorrhagic
      infarct and subarachnoid hemorrhage when compared with those without. Patients
      with only periventricular LA did not have a higher rate of parenchymal hematoma.
      Moderate or severe LA in the DWM was an independent predictor of hemorrhagic
      transformation (OR, 3.4; P=0.019) and parenchymal hematoma (OR, 6.3; P=0.005).
      Patients with parenchymal hematoma were less often independent (modified Rankin
      Scale<=2, 3.8% versus 32.5%; P=0.003) and had greater in-hospital mortality (50%
      versus 10.4%; P<0.001). CONCLUSIONS: Moderate or severe LA in the DWM increases
      the risk of parenchymal hematoma after Merci thrombectomy for patients with acute
      stroke. These findings require validation in a larger prospective study.

PMID- 22581821
TI  - Theta burst stimulation over the right Broca's homologue induces improvement of
      naming in aphasic patients.
AB  - BACKGROUND AND PURPOSE: Improvements of language production in aphasic patients
      have been reported following repeated 1-Hz transcranial magnetic stimulation over
      the nondamaged right hemisphere. Most studies examined aphasic patients in the
      chronic phase. The effect of transcranial magnetic stimulation application in
      acute or subacute patients has not been systematically studied. We aimed to
      evaluate whether continuous theta burst stimulation, an inhibitory protocol with
      a shorter application time than the common 1-Hz protocol, is able to improve
      naming performance in aphasic patients in different poststroke phases. METHODS:
      Eighteen right-handed aphasic patients performed a picture naming task and a
      language independent alertness test before and after the application of theta
      burst stimulation over the intact right Broca's homologue localized by the 10-20
      electroencephalogram system in a randomized, sham-controlled, crossover trial.
      RESULTS: We found that naming performance was significantly better, and naming
      latency was significantly shorter, after theta burst stimulation than after the
      sham intervention. Patients who responded best were in the subacute phase after
      stroke. CONCLUSIONS: This setting with the short theta burst stimulation
      application time and the simple stimulation localization procedure is suitable
      for clinical purposes.

PMID- 22581822
TI  - Quality of life with gefitinib in patients with EGFR-mutated non-small cell lung
      cancer: quality of life analysis of North East Japan Study Group 002 Trial.
AB  - BACKGROUND: For non-small cell lung cancer (NSCLC) patients with epidermal growth
      factor receptor (EGFR) mutations, first-line gefitinib produced a longer
      progression-free survival interval than first-line carboplatin plus paclitaxel
      but did not show any survival advantage in the North East Japan 002 study. This
      report describes the quality of life (QoL) analysis of that study. METHODS:
      Chemotherapy-naive patients with sensitive EGFR-mutated, advanced NSCLC were
      randomized to receive gefitinib or chemotherapy (carboplatin and paclitaxel).
      Patient QoL was assessed weekly using the Care Notebook, and the primary endpoint
      of the QoL analysis was time to deterioration from baseline on each of the
      physical, mental, and life well-being QoL scales. Kaplan-Meier probability curves
      and log-rank tests were employed to clarify differences. RESULTS: QoL data from
      148 patients (72 in the gefitinib arm and 76 in the carboplatin plus paclitaxel
      arm) were analyzed. Time to defined deterioration in physical and life well-being
      significantly favored gefitinib over chemotherapy (hazard ratio [HR] of time to
      deterioration, 0.34; 95% confidence interval [CI], 0.23-0.50; p < .0001 and HR,
      0.43; 95% CI, 0.28-0.65; p < .0001, respectively). CONCLUSION: QoL was maintained
      much longer in patients treated with gefitinib than in patients treated with
      standard chemotherapy, indicating that gefitinib should be considered as the
      standard first-line therapy for advanced EGFR-mutated NSCLC in spite of no
      survival advantage.

PMID- 22581823
TI  - Clinical management and outcome of refractory asthma in the UK from the British
      Thoracic Society Difficult Asthma Registry.
AB  - Refractory asthma represents a significant unmet clinical need. Data from a
      national online registry audited clinical outcome in 349 adults with refractory
      asthma from four UK specialist centres in the British Thoracic Society Difficult
      Asthma Network. At follow-up, lung function improved, with a reduction in
      important healthcare outcomes, specifically hospital admission, unscheduled
      healthcare visits and rescue courses of oral steroids. The most frequent
      therapeutic intervention was maintenance oral corticosteroids and most steroid
      sparing agents (apart from omalizumab) demonstrated minimal steroid sparing
      benefit. A significant unmet clinical need remains in this group, specifically a
      requirement for therapies which reduce systemic steroid exposure.

PMID- 22581824
TI  - IL-10 directly activates and expands tumor-resident CD8(+) T cells without de
      novo infiltration from secondary lymphoid organs.
AB  - The presence of activated intratumoral T cells correlates clinically with better
      prognosis in patients with cancer. Although tumor vaccines can increase the
      number of tumor-specific CD8(+) T cells in systemic circulation, they frequently
      fail to increase the number of active and tumor reactive T cells within the
      tumor. Here we show that treatment with the pleiotropic cytokine interleukin-10
      (IL-10) induces specific activation of tumor-resident CD8(+) T cells as well as
      their intratumoral expansion in several mouse tumor models. We found that
      inhibition of T-cell trafficking from lymphoid organs did not impair IL-10
      induced tumor rejection or the activation of tumor-resident CD8(+) T cells. Tumor
      resident CD8(+) T cells expressed elevated levels of the IL-10 receptor and were
      directly activated by IL-10, resulting in prominent phosphorylation of STAT3 and
      STAT1. Although CD4(+) T cells, regulatory T cells, NK cells, and dendritic cells
      have been reported as prominent targets of IL-10 in the tumor microenvironment,
      we found that expression of the IL-10R was required only on CD8(+) T cells to
      facilitate IL-10-induced tumor rejection as well as in situ expansion and
      proliferation of tumor-resident CD8 T cells. Together, our findings indicate that
      IL-10 activates CD8(+) T-cell-mediated tumor control and suggest that IL-10 may
      represent a potential tumor immunotherapy in human patients with cancer.

PMID- 22581825
TI  - Ultrasensitive measurement of hotspot mutations in tumor DNA in blood using error
      suppressed multiplexed deep sequencing.
AB  - Detection of cell-free tumor DNA in the blood has offered promise as a cancer
      biomarker, but practical clinical implementations have been impeded by the lack
      of a sensitive and accurate method for quantitation that is also simple,
      inexpensive, and readily scalable. Here we present an approach that uses next
      generation sequencing to quantify the small fraction of DNA molecules that
      contain tumor-specific mutations within a background of normal DNA in plasma.
      Using layers of sequence redundancy designed to distinguish true mutations from
      sequencer misreads and PCR misincorporations, we achieved a detection sensitivity
      of approximately 1 variant in 5,000 molecules. In addition, the attachment of
      modular barcode tags to the DNA fragments to be sequenced facilitated the
      simultaneous analysis of more than 100 patient samples. As proof-of-principle, we
      showed the successful use of this method to follow treatment-associated changes
      in circulating tumor DNA levels in patients with non-small cell lung cancer. Our
      findings suggest that the deep sequencing approach described here may be applied
      to the development of a practical diagnostic test that measures tumor-derived DNA
      levels in blood.

PMID- 22581827
TI  - FOXM1 mediates Dox resistance in breast cancer by enhancing DNA repair.
AB  - Transcription factors are direct effectors of altered signaling pathways in
      cancer and frequently determine clinical outcomes in cancer patients. To uncover
      new transcription factors that would determine clinical outcomes in breast
      cancer, we systematically analyzed gene expression data from breast cancer
      patients. Our results revealed that Forkhead box protein M1 (FOXM1) is the top
      ranked survival-associated transcription factor in patients with triple-negative
      breast cancer. Surprisingly, silencing FOXM1 expression led breast cancer cells
      to become more sensitive to doxorubicin (Dox). We found that FOXM1-dependent
      resistance to Dox is mediated by regulating DNA repair genes. We further
      demonstrated that NFkappaB1 interacts with FOXM1 in the presence of Dox to
      protect breast cancer cells from DNA damage. Finally, silencing FOXM1 expression
      in breast cancer cells in a mouse xenograft model significantly sensitized the
      cells to Dox. Our systematic approaches identified an unexpected role of FOXM1 in
      Dox resistance by regulating DNA repair genes, and our findings provide
      mechanistic insights into how FOXM1 mediates resistance to Dox and evidence that
      FOXM1 may be a promising therapeutic target for sensitizing breast cancer cells
      to Dox.

PMID- 22581828
TI  - Activation of the Notch1/STAT3/Twist signaling axis promotes gastric cancer
      progression.
AB  - Gastric carcinoma is one of the most common malignancies and a lethal cancer in
      the world. Notch signaling and transcription factors STAT3 (signal transducer and
      activator of transcription 3) and Twist regulate tumor development and are
      critical regulators of gastric cancer progression. Herein, the relationship among
      Notch, STAT3 and Twist pathways in the control of gastric cancer progression was
      studied. We found that Twist and phosphorylated STAT3 levels were promoted by the
      activated Notch1 receptor in human stomach adenocarcinoma SC-M1, embryonic kidney
      HEK293 and erythroleukemia K562 cells. Notch1 signaling dramatically induced
      Twist promoter activity through a C promoter binding factor-1-independent manner
      and STAT3 phosphorylation. Overexpression of Notch1 receptor intracellular domain
      (N1IC) enhanced the interaction between nuclear STAT3 and Twist promoter in
      cells. Gastric cancer progression of SC-M1 cells was promoted by N1IC through
      STAT3 phosphorylation and Twist expression including colony formation, migration
      and invasion. STAT3 regulated gastric cancer progression of SC-M1 cells via
      Twist. N1IC also elevated the progression of other gastric cancer cells such as
      AGS and KATO III cells through STAT3 and Twist. The N1IC-promoted tumor growth
      and lung metastasis of SC-M1 cells in mice were suppressed by the STAT3 inhibitor
      JSI-124 and Twist knockdown. Furthermore, Notch1 and Notch ligand Jagged1
      expressions were significantly associated with phosphorylated STAT3 and Twist
      levels in gastric cancer tissues of patients. Taken together, these results
      suggest that Notch1/STAT3/Twist signaling axis is involved in progression of
      human gastric cancer and modulation of this cascade has potential for the
      targeted combination therapy.

PMID- 22581829
TI  - MicroRNA-93 inhibits tumor growth and early relapse of human colorectal cancer by
      affecting genes involved in the cell cycle.
AB  - PURPOSE: Colorectal cancer (CRC) is associated with high recurrence and
      mortality. Because deregulation of microRNAs is associated with CRC development
      and recurrence, the expression levels of microRNAs can be a simple and reliable
      biomarker to detect postoperative early relapse, thereby helping physicians to
      treat high-risk patients more efficiently. EXPERIMENTAL DESIGN: We used microRNA
      arrays and observed that microRNA-93 had substantially different expression
      levels in early (recurrence within 12 months after surgery) and non-early relapse
      CRC patients. The replication study, which included 35 early relapse and 42 non
      early relapse subjects, further confirmed overexpression of microRNA-93 in non
      early relapse samples. The in vitro and in vivo effects of microRNA-93 were
      investigated by examining cell proliferation, migration and invasion, as well as
      cell cycles, target-gene expression and xenograft in null mice. RESULTS: Cellular
      studies showed that the overexpression of microRNA-93 inhibited colon cancer cell
      proliferation and migration but not invasion. The cell cycle studies also
      revealed that microRNA-93 caused an accumulation of the G2 population. However,
      microRNA-93 could not induce cell apoptosis or necrosis. Functional studies
      showed that microRNA-93 could suppress CCNB1 protein expression leading to cell
      cycle arrest in the G2 phase. Moreover, microRNA-93 repressed expression of
      ERBB2, p21 and VEGF, all of which are involved in cell proliferation. MicroRNA-93
      also suppressed tumor growth in null mice. CONCLUSIONS: This study showed that
      microRNA-93 can inhibit tumorigenesis and reduce the recurrence of CRC; these
      findings may have potential clinical applications for predicting the recurrence
      of CRC.

PMID- 22581830
TI  - Subchronic exposure to arsenic inhibits spermatogenesis and downregulates the
      expression of ddx3y in testis and epididymis of mice.
AB  - Arsenic (As) is a ubiquitous environmental contaminant. Excess As exposure is
      considered one of the top health threats worldwide. As-induced Male reproductive
      toxicity is causing wide concern. The goal of this study is to determine whether
      subchronic As exposure inhibits Ddx3y expression, an Y-linked gene important in
      spermatogenesis and sperm maturation, and whether the inhibited expression of
      Ddx3y is closely associated with As-induced male reproductive toxicity Adult mice
      were given drinking water alone or water containing 1, 2, and 4mg/l arsenic
      trioxide (As(2)O(3)) for 60 days. After the treatment, the weights of testis and
      epididymis were analyzed. The sperm quality, spermatogenesis, and histological
      alteration of the testis and epididymis were observed by microscope. Furthermore,
      the expressions of Ddx3y gene and its protein in the testis and epididymis were
      examined by real-time reverse transcription PCR, Western blotting, and
      immunohistochemistry. Compared with untreated mice, the weights of testis and
      epididymis were reduced, sperm motility and the number of stage VII cells in the
      seminiferous epithelium section were decreased, sperm malformation ratio was
      increased, and histopathological alterations were observed in As-treated mice.
      The gene and protein expression of Ddx3y in testis and epididymis were
      significantly downregulated in As-exposed mice. Subchronic As exposure has
      detrimental effects on spermatogenesis and sperm development. It also
      downregulates Ddx3y expressions in testis and epididymis. Our results indicated
      that Ddx3y may be an important target gene of As and the downregulated expression
      of Ddx3y may be closely related to male reproductive toxicity induced by As.

PMID- 22581831
TI  - Ninety-day inhalation toxicity study with a vapor grown carbon nanofiber in rats.
AB  - A subchronic inhalation toxicity study of inhaled vapor grown carbon nanofibers
      (CNF)  (VGCF-H) was conducted in male and female Sprague Dawley rats. The CNF
      test sample was composed of > 99.5% carbon with virtually no catalyst metals;
      Brunauer, Emmett, and Teller (BET) surface area measurements of 13.8 m2/g; and
      mean lengths and diameters of 5.8 um and 158 nm, respectively.Four groups of rats
      per sex were exposed nose-only, 6 h/day, for 5 days/week to target concentrations
      of 0, 0.50, 2.5, or 25 mg/m3 VGCF-H over a 90-day period and evaluated 1 day
      later. Assessments included conventional clinical and histopathological methods,
      bronchoalveolar lavage fluid (BALF) analysis, and cell proliferation (CP) studies
      of the terminal bronchiole (TB), alveolar duct (AD), and subpleural regions of
      the respiratory tract. In addition, groups of  0 and 25 mg/m3 exposed rats were
      evaluated at 3 months postexposure (PE). Aerosol exposures of rats to 0.54 (4.9
      f/cc), 2.5 (56 f/cc), and 25 (252 f/cc) mg/m(3) of VGCF-H CNFs produced
      concentration-related small, detectable accumulation of extrapulmonary fibers
      with no adverse tissue effects. At the two highest concentrations, inflammation
      of the TB and AD regions of the respiratory tract was noted wherein fiber-laden
      alveolar macrophages had accumulated. This finding was characterized by minimal
      infiltrates of inflammatory cells in rats exposed to 2.5mg/m(3) CNF, inflammation
      along with some thickening of interstitial walls, and hypertrophy/hyperplasia of
      type II epithelial cells, graded as slight for the 25mg/m(3) concentration. At 3
      months PE, the inflammation in the high dose was reduced. No adverse effects were
      observed at 0.54mg/m(3). BALF and CP endpoint increases versus controls were
      noted at 25mg/m(3) VGCF-H but not different from control values at 0.54 or
      2.5mg/m(3). After 90 days PE, BALF biomarkers were still increased at 25mg/m(3),
      indicating that the inflammatory response was not fully resolved. Greater than
      90% of CNF-exposed, BALF-recovered alveolar macrophages from the 25 and
      2.5mg/m(3) exposure groups contained nanofibers (> 60% for 0.5mg/m(3)). A
      nonspecific inflammatory response was also noted in the nasal passages. The no
      observed-adverse-effect level for VGCF-H nanofibers was considered to be
      0.54mg/m(3) (4.9 fibers/cc) for male and female rats, based on the minimal
      inflammation in the terminal bronchiole and alveolar duct areas of the lungs at
      2.5mg/m(3) exposures. It is noteworthy that the histopathology observations at
      the 2.5mg/m(3) exposure level did not correlate with the CP or BALF data at that
      exposure concentration. In addition, the results with CNF are compared with
      published findings of 90-day inhalation studies in rats with carbon nanotubes,
      and hypotheses are presented for potency differences based on CNT physicochemical
      characteristics. Finally, the (lack of) relevance of CNF for the high aspect
      ratio nanomaterials/fiber paradigm is discussed.

PMID- 22581832
TI  - MicroRNAs: Synthesis, Gene Regulation and Osteoblast Differentiation.
AB  - The central dogma of transfer of genetic information from DNA to protein via mRNA
      is now challenged by small fragment of non coding RNAs typically 19-25
      nucleotides in length namely microRNAs (miRNAs). miRNAs regulate expression of
      the protein coding genes by interfering in their mRNAs and, thus, act as key
      regulators of diverge cellular activities. Osteoblast differentiation, a key step
      in skeletal development involves activation of several signalling pathways
      including TGFb, BMP, Wnt and transcription factors, which are tightly regulated
      by miRNAs. In this review, we provide information on recent developments of the
      synthesis and gene regulation of miRNAs as well as the potential nature of miRNAs
      that regulate mesenchymal stem cell towards osteoblast differentiation for
      therapeutic purpose.

PMID- 22581835
TI  - Stromal adipocyte PPARgamma protects against breast tumorigenesis.
AB  - Peroxisome proliferator-activated receptor (PPAR)gamma regulates the expression
      of genes essential for fat storage, primarily through its activity in adipocytes.
      It also has a role in carcinogenesis. PPARgamma normally stops the in vivo
      progression of 7,12-dimethylbenz[a]anthracene (DMBA)-mediated breast tumours as
      revealed with PPARgamma haploinsufficient mice. Since many cell types associated
      with the mammary gland express PPARgamma, each with unique signal patterns, this
      study aimed to define which tissues are required for PPARgamma-dependent
      antitumour effects. Accordingly, adipocyte-specific PPARgamma knockout (PPARgamma
      A KO) mice and their wild-type (PPARgamma-WT) controls were generated, and
      treated with DMBA for 6 weeks to initiate breast tumorigenesis. On week 7, mice
      were randomized to continue on normal chow diet or one supplemented with
      rosiglitazone (ROSI), and followed for 25 weeks for tumour outcomes. In PPARgamma
      A KO versus PPARgamma-WT mice, malignant mammary tumour incidence was
      significantly higher and mammary tumour latency was decreased. DMBA + ROSI
      treatment reduced average mammary tumour volumes by 50%. Gene expression analyses
      of mammary glands by quantitative real-time polymerase chain reaction and
      immunofluorescence indicated that untreated PPARgamma-A KOs had significantly
      decreased BRCA1 expression in mammary stromal adipocytes. Compared with PPARgamma
      WT mice, serum leptin levels in PPARgamma-A KOs were also significantly higher
      throughout the study. Together, these data are the first to suggest that in vivo
      PPARgamma expression in mammary stromal adipocytes attenuates breast
      tumorigenesis through BRCA1 upregulation and decreased leptin secretion. This
      study supports a protective effect of activating PPARgamma as a novel
      chemopreventive therapy for breast cancer.

PMID- 22581836
TI  - Polymorphisms in miRNA-binding sites of nucleotide excision repair genes and
      colorectal cancer risk.
AB  - Reduced DNA repair capacity and DNA damage accumulation may lead to cancer
      development. Regulation of and coordination between genes involved in DNA repair
      pathways is fundamental for maintaining genome stability, and post
      transcriptional gene regulation by microRNAs (miRNAs) may therefore be of
      particular relevance. In this context, the presence of single nucleotide
      polymorphisms (SNPs) within the 3'untranslated regions of target DNA repair genes
      could alter the binding with specific miRNAs, modulating gene expression and
      ultimately affecting cancer susceptibility. In this study, we investigated the
      role of genetic variations in miRNA-binding sites of nucleotide excision repair
      (NER) genes in association with colorectal cancer (CRC) risk. From 28 NER genes,
      we screened among SNPs residing in their 3'untranslated regions and
      simultaneously located in miRNA-binding sites, with an in silico approach.
      Through the calculation of different binding free energy according to both
      alleles of identified SNPs, and with global binding free energies median
      providing a threshold, we selected nine NER gene variants. We tested those SNPs
      in 1098 colorectal cancer cases and 1469 healthy controls from the Czech
      Republic. Rs7356 in RPA2 and rs4596 in GTF2H1 were associated with colorectal
      cancer risk. After stratification for tumor location, the association of both
      SNPs was significant only for rectal cancer (rs7356: OR 1.52, 95% CI 1.02-2.26, P
      = 0.04 and rs4596: OR 0.69, 95% CI 0.50-0.94, P = 0.02; results not adjusted for
      multiple testing). Variation in miRNA target binding sites in the 3'untranslated
      region of NER genes may be important for modulating colorectal cancer risk, with
      a different relevance according to tumor location.

PMID- 22581837
TI  - Nuclear epidermal growth factor receptor interacts with transcriptional
      intermediary factor 2 to activate cyclin D1 gene expression triggered by the
      oncoprotein latent membrane protein 1.
AB  - The epidermal growth factor receptor (EGFR), a ubiquitously expressed receptor
      tyrosine kinase, is an important factor in carcinogenesis. Transcriptional
      intermediary factor 2 (TIF2), a member of the p160 nuclear receptor co-activator
      gene family, is linked to the proliferation of cancer cells. However, the direct
      interplay between the EGFR and the nuclear receptors remains unclear. Our
      previous study demonstrated that nuclear EGFR could directly bind to the cyclin
      D1 promoter under the regulation of the oncoprotein latent membrane protein 1
      (LMP1), but it also indicated that other factors are involved in the activation
      of target genes. In this study, we found that LMP1 upregulated the expression of
      TIF2 and promoted the interaction of EGFR with TIF2 in nasopharyngeal carcinoma.
      Furthermore, we demonstrated that the intact complex was linked with cyclin D1
      promoter activity in an LMP1-dependent manner. The physiological functions of the
      intact complex were associated with cell proliferation and cell cycle
      progression. These findings suggest that TIF2 is a novel binding partner for
      nuclear EGFR and is involved in regulating its target gene expression.

PMID- 22581838
TI  - A population-based study of DNA repair gene variants in relation to non-melanoma
      skin cancer as a marker of a cancer-prone phenotype.
AB  - For unknown reasons, non-melanoma skin cancer (NMSC) is associated with increased
      risk of other malignancies. Focusing solely on DNA repair or DNA repair-related
      genes, this study tested the hypothesis that DNA repair gene variants contribute
      to the increased cancer risk associated with a personal history of NMSC. From the
      parent CLUE II cohort study, established in 1989 in Washington County, MD, the
      study consisted of a cancer-free control group (n 5 2296) compared with three
      mutually exclusive groups of cancer cases ascertained through 2007: (i) Other
      (non-NMSC) cancer only (n 5 2349); (ii) NMSC only (n 5 694) and (iii) NMSC plus
      other cancer (n 5 577). The frequency of minor alleles in 759 DNA repair gene
      single nucleotide polymorphisms (SNPs) was compared in these four groups.
      Comparing those with both NMSC and other cancer versus those with no cancer, 10
      SNPs had allelic trend P-values <0.01. The two top-ranked SNPs were both within
      the thymine DNA glycosylase gene (TDG). One was a non-synonymous coding SNP
      (rs2888805) [per allele odds ratio (OR) 1.40, 95% confidence interval (CI) 1.16
      1.70; P-value 5 0.0006] and the other was an intronic SNP in high linkage
      disequilibrium with rs2888805 (rs4135150). None of the associations had a P-value
      <6.6310(-5), the threshold for statistical significance after correcting for
      multiple comparisons. The results pinpoint DNA repair genes most likely to
      contribute to the NMSC cancer-prone phenotype. A promising lead is genetic
      variants in TDG, important not only in base excision repair but also in
      regulating the epigenome and gene expression, which may contribute to the NMSC
      associated increase in overall cancer risk.

PMID- 22581839
TI  - The TFG-TEC fusion gene created by the t(3;9) translocation in human
      extraskeletal myxoid chondrosarcomas encodes a more potent transcriptional
      activator than TEC.
AB  - The t(3;9)(q11-q12;q22) translocation associated with human extraskeletal myxoid
      chondrosarcomas results in a chimeric molecule in which the N-terminal domain
      (NTD) of the TFG (TRK-fused gene) is fused to the TEC (Translocated in
      Extraskeletal Chondrosarcoma) gene. Little is known about the biological function
      of TFG-TEC. Because the NTDs of TFG-TEC and TEC are structurally different, and
      the TFG itself is a cytoplasmic protein, the functional consequences of this
      fusion in extraskeletal myxoid chondrosarcomas were examined. The results showed
      that the chimeric gene encoded a nuclear protein that bound DNA with the same
      sequence specificity as the parental TEC protein. Comparison of the
      transactivation properties of TFG-TEC and TEC indicated that the former has
      higher transactivation activity for a known target reporter containing TEC
      binding sites. Additional reporter assays for TFG (NTD) showed that the TGF (NTD)
      of TFG-TEC induced a 12-fold increase in the activation of luciferase from a
      reporter plasmid containing GAL4 binding sites when fused to the DNA-binding
      domain of GAL4, indicating that the TFG (NTD) of the TFG-TEC protein has
      intrinsic transcriptional activation properties. Finally, deletion analysis of
      the functional domains of TFG (NTD) indicated that the PB1 (Phox and Bem1p) and
      SPYGQ-rich region of TFG (NTD) were capable of activating transcription and that
      full integrity of TFG (NTD) was necessary for full transactivation. These results
      suggest that the oncogenic effect of the t(3;9) translocation may be due to the
      TFG-TEC chimeric protein and that fusion of the TFG (NTD) to the TEC protein
      produces a gain-of-function chimeric product.

PMID- 22581840
TI  - Chemopreventive sphingadienes downregulate Wnt signaling via a PP2A/Akt/GSK3beta
      pathway in colon cancer.
AB  - Sphingadienes (SDs) derived from soy and other natural sphingolipids are
      cytotoxic to colon cancer cells via an Akt-dependent mechanism and reduce adenoma
      formation in Apc(Min/+) mice. Wnt signaling is fundamental to colon
      carcinogenesis and is the basis for spontaneous tumorigenesis in Apc(Min/+) mice
      and patients with familial adenomatous polyposis. In the present study, we
      investigated the impact of SDs on Wnt signaling. Oral SD administration reduced
      levels of active beta-catenin and Wnt targets c-Myc and cyclin D1 in Apc(Min/+)
      mouse intestinal tissues. Colon cancer cells treated with SDs exhibited reduced
      Wnt transcriptional activity, as well as reduced nuclear beta-catenin
      localization and subsequent reduction in active-beta-catenin levels. Further, we
      observed a decrease in phosphorylated (inactive) GSK3beta in SD-treated mice and
      colon cancer cells. Expression of constitutively active myristoylated-Akt or
      inactivation of GSK3beta using LiCl attenuated SD-mediated inhibition of Wnt
      transcriptional activity and active-beta-catenin levels. SDs exhibited additive
      effects with inhibitors of the phosphatidylinositol-3-kinase/Akt/mTOR pathway to
      induce cytotoxicity. Further, a combination regime of SDs and low-dose rapamycin
      decreased visible polyps in Apc(Min/+) mice and reduced the levels of Wnt target
      gene expression and mTOR target activation. SD-mediated inhibition of Akt and Wnt
      pathways and cytotoxicity in colon cancer cells was dependent upon the activity
      of protein phosphatase 2A, as shown by reversal of these effects by pretreatment
      with okadaic acid or calyculin A. Our cumulative findings indicate that SDs
      inhibit Wnt signaling through a protein phosphatase 2A/Akt/GSK3beta-dependent
      mechanism that may contribute to their chemopreventive effects in intestinal
      tumorigenesis.

PMID- 22581842
TI  - Variation in HMA4 gene copy number and expression among Noccaea caerulescens
      populations presenting different levels of Cd tolerance and accumulation.
AB  - There is huge variability among populations of the hyperaccumulator Noccaea
      caerulescens (formerly Thlaspi caerulescens) in their capacity to tolerate and
      accumulate cadmium. To gain new insights into the mechanisms underlying this
      variability, we estimated cadmium fluxes and further characterized the N.
      caerulescens heavy metal ATPase 4 (NcHMA4) gene in three populations (two
      calamine, Saint-Felix-de-Pallieres, France and Prayon, Belgium; one serpentine,
      Puente Basadre, Spain) presenting contrasting levels of tolerance and
      accumulation. Cadmium uptake and translocation varied among populations in the
      same way as accumulation; the population with the highest cadmium concentration
      in shoots (Saint Felix-de-Pallieres) presented the highest capacity for uptake
      and translocation. We demonstrated that the four NcHMA4 copies identified in a
      previous study are not fixed at the species level, and that the copy truncated in
      the C-terminal part encodes a functional protein. NcHMA4 expression and gene copy
      number was lower in the serpentine population, which was the least efficient in
      cadmium translocation compared to the calamine populations. NcHMA4 expression was
      associated with the vascular tissue in all organs, with a maximum at the crown.
      Overall, our results indicate that differences in cadmium translocation ability
      of the studied populations appear to be controlled, at least partially, by
      NcHMA4, while the overexpression of NcHMA4 in the two calamine populations may
      result from convergent evolution.

PMID- 22581841
TI  - Global DNA methylation levels in white blood cells as a biomarker for
      hepatocellular carcinoma risk: a nested case-control study.
AB  - Global DNA hypomethylation is associated with genomic instability and human
      cancer and blood DNAs collected at the time of cancer diagnosis have been used to
      examine the relationship between global methylation and cancer risk. To test the
      hypothesis that global hypomethylation is associated with increased risk of
      hepatocellular carcinoma (HCC), we conducted a prospective case-control study
      nested within a community-based cohort with 16 years of follow-up. We measured
      methylation levels in Satellite 2 (Sat2) by MethyLight and LINE-1 by
      pyrosequencing using baseline white blood cell DNA from 305 HCC cases and 1254
      matched controls. We found that Sat2 hypomethylation was associated with HCC risk
      [odds ratio (OR) per unit decrease in natural log Sat2 methylation = 1.77, 95%
      confidence interval (CI) = 1.06-2.95]. The association was significant among
      individuals diagnosed with HCC before age 62 (OR per unit decrease in natural log
      Sat2 methylation = 2.47, 95% CI = 1.06-5.73) but not after (OR = 1.67, 95% CI =
      0.84-3.32). We did not observe an association of LINE-1 with HCC overall risk by
      age at diagnosis. Among carriers of hepatitis B virus surface antigen (HBsAg),
      with each 1U decrease in natural log Sat2 methylation level, the OR for HCC
      increased by 2.19 (95% CI = 1.00-4.89). LINE-1 hypomethylation was associated
      with about a 2-fold increased risk of HCC, with ORs (95% CI) of 2.39 (1.06-5.39),
      2.09 (0.91-4.77) and 2.28 (0.95-5.51, P(trend) = 0.14) for HBsAg carriers in the
      third, second and lowest quartile of LINE-1 methylation, respectively compared
      with carriers in the fourth. These results suggest that global hypomethylation
      may be a useful biomarker of HCC susceptibility.

PMID- 22581844
TI  - Reproductive biology of the Cape honeybee: a critique of Beekman et al.
AB  - Laying workers of the Cape honeybee parthenogenetically produce female offspring,
      whereas queens typically produce males. Beekman et al. confirm this observation,
      which has repeatedly been reported over the last 100 years including the notion
      that natural selection should favor asexual reproduction in Apis mellifera 
      capensis. They attempt to support their arguments with an exceptionally
      surprising finding that A. m. capensis queens can parthenogenetically produce
      diploid homozygous queen offspring (homozygous diploid individuals develop into
      diploid males in the honeybee). Beekman et al. suggest that these homozygous
      queens are not viable because they did not find any homozygous individuals beyond
      the third larval instar. Even if this were true, such a lethal trait should be
      quickly eliminated by natural selection. The identification of sex (both with
      molecular and morphological markers) is possible but notoriously difficult in
      honeybees at the early larval stages. Ploidy is however a reliable indicator, and
      we therefore suggest that these "homozygous" larvae found in queen cells are
      actually drones reared from unfertilized eggs, a phenomenon well known by
      honeybee queen breeders.

PMID- 22581846
TI  - Auditory-motor processing of speech sounds.
AB  - The motor regions that control movements of the articulators activate during
      listening to speech and contribute to performance in demanding speech recognition
      and discrimination tasks. Whether the articulatory motor cortex modulates
      auditory processing of speech sounds is unknown. Here, we aimed to determine
      whether the articulatory motor cortex affects the auditory mechanisms underlying
      discrimination of speech sounds in the absence of demanding speech tasks. Using
      electroencephalography, we recorded responses to changes in sound sequences,
      while participants watched a silent video. We also disrupted the lip or the hand
      representation in left motor cortex using transcranial magnetic stimulation.
      Disruption of the lip representation suppressed responses to changes in speech
      sounds, but not piano tones. In contrast, disruption of the hand representation
      had no effect on responses to changes in speech sounds. These findings show that
      disruptions within, but not outside, the articulatory motor cortex impair
      automatic auditory discrimination of speech sounds. The findings provide evidence
      for the importance of auditory-motor processes in efficient neural analysis of
      speech sounds.

PMID- 22581847
TI  - Sports concussions and aging: a neuroimaging investigation.
AB  - Recent epidemiological and experimental studies suggest a link between cognitive
      decline in late adulthood and sports concussions sustained in early adulthood. In
      order to provide the first in vivo neuroanatomical evidence of this relation, the
      present study probes the neuroimaging profile of former athletes with concussions
      in relation to cognition. Former athletes who sustained their last sports
      concussion >3 decades prior to testing were compared with those with no history
      of traumatic brain injury. Participants underwent quantitative neuroimaging
      (optimized voxel-based morphometry [VBM], hippocampal volume, and cortical
      thickness), proton magnetic resonance spectroscopy ((1)H MRS; medial temporal
      lobes and prefrontal cortices), and neuropsychological testing, and they were
      genotyped for APOE polymorphisms. Relative to controls, former athletes with
      concussions exhibited: 1) Abnormal enlargement of the lateral ventricles, 2)
      cortical thinning in regions more vulnerable to the aging process, 3) various
      neurometabolic anomalies found across regions of interest, 4) episodic memory and
      verbal fluency decline. The cognitive deficits correlated with neuroimaging
      findings in concussed participants. This study unveiled brain anomalies in
      otherwise healthy former athletes with concussions and associated those
      manifestations to the long-term detrimental effects of sports concussion on
      cognitive function. Findings from this study highlight patterns of decline often
      associated with abnormal aging.

PMID- 22581848
TI  - Methylphenidate effects on neural activity during response inhibition in healthy
      humans.
AB  - Methylphenidate (MPH) is a catecholamine transporter blocker, with dopamine
      agonistic effects in the basal ganglia. Response inhibition, error detection, and
      its mediating frontostriatal brain activation are improved by MPH in patients
      with attention-deficit/hyperactivity disorder. However, little is known about the
      effects of MPH on response inhibition and error processing or its underlying
      brain function in healthy individuals. Therefore, this study employed functional
      magnetic resonance imaging (fMRI) and 2 response inhibition tasks in 52 healthy
      males. Subjects underwent fMRI during a go/no-go task and a tracking stop-signal
      task after administration of 40 mg MPH and placebo in a double-blind, placebo
      controlled, repeated-measures design. Results revealed task- and condition
      specific neural effects of MPH: it increased activation in the putamen only
      during inhibition errors but not during successful inhibition and only in the
      go/no-go task. We speculate that task specificity of the effect might be due to
      differences in the degree of error saliency in the 2 task designs, whereas errors
      were few in the go/no-go task and thus had high saliency and the stop-signal task
      was designed to elicit 50% of errors in all subjects, diminishing the error
      saliency effect. The findings suggest that neural MPH effects interact with the
      saliency of the behavior under investigation.

PMID- 22581845
TI  - Calpains, mitochondria, and apoptosis.
AB  - Mitochondrial activity is critical for efficient function of the cardiovascular
      system. In response to cardiovascular injury, mitochondrial dysfunction occurs
      and can lead to apoptosis and necrosis. Calpains are a 15-member family of Ca(2+)
      activated cysteine proteases localized to the cytosol and mitochondria, and
      several have been shown to regulate apoptosis and necrosis. For example, in
      endothelial cells, Ca(2+) overload causes mitochondrial calpain 1 cleavage of the
      Na(+)/Ca(2+) exchanger leading to mitochondrial Ca(2+) accumulation. Also,
      activated calpain 1 cleaves Bid, inducing cytochrome c release and apoptosis. In
      renal cells, calpains 1 and 2 promote apoptosis and necrosis by cleaving
      cytoskeletal proteins, which increases plasma membrane permeability and cleavage
      of caspases. Calpain 10 cleaves electron transport chain proteins, causing
      decreased mitochondrial respiration and excessive activation, or inhibition of
      calpain 10 activity induces mitochondrial dysfunction and apoptosis. In
      cardiomyocytes, calpain 1 activates caspase 3 and poly-ADP ribose polymerase
      during tumour necrosis factor-alpha-induced apoptosis, and calpain 1 cleaves
      apoptosis-inducing factor after Ca(2+) overload. Many of these observations have
      been elucidated with calpain inhibitors, but most calpain inhibitors are not
      specific for calpains or a specific calpain family member, creating more
      questions. The following review will discuss how calpains affect mitochondrial
      function and apoptosis within the cardiovascular system.

PMID- 22581849
TI  - Opposing alterations in excitation and inhibition of layer 5 medial prefrontal
      cortex pyramidal neurons following neonatal ventral hippocampal lesion.
AB  - Cognitive abnormalities in schizophrenia reflect deficits in prefrontal cortical
      function, which could be related to attrition of dendritic structures of
      prefrontal cortical neurons. Schizophrenia-related prefrontal deficits have been
      modeled in postpubertal neonatal ventral hippocampal lesioned (NVHL) rats, which
      displayed a loss of dendritic complexity and spines in layer 3 pyramidal neurons
      in the medial prefrontal cortex (mPFC). The influence of dendritic attrition on
      synaptic function and neuronal excitability in the mPFC remains poorly
      understood. Here, we performed electrophysiological recordings of layer 5 mPFC
      pyramidal neurons from postpubertal (postnatal 40-60 days) NVHL rats and sham
      operated controls. We found that the dendritic length, complexity, and spine
      density of neurobiotin-labeled layer 5 mPFC pyramidal neurons in NVHL rats were
      significantly lower than those in sham-operated rats. However, the excitability
      of layer 5 mPFC pyramidal neurons remained unchanged after NVHL. We found no
      significant changes in the expression of vesicular glutamate and gamma
      aminobutyric acid transporters after NVHL. Intriguingly, NVHL increased the
      amplitude of action potential-independent miniature excitatory postsynaptic
      currents and decreased the frequency of miniature inhibitory postsynaptic
      currents. These opposing alterations in excitatory and inhibitory synapses,
      possibly shifting basal synaptic activity toward increased excitation, could be
      cellular substrates for mPFC functional deficits reported in NVHL rats.

PMID- 22581850
TI  - Astrocyte calcium signal and gliotransmission in human brain tissue.
AB  - Brain function is recognized to rely on neuronal activity and signaling processes
      between neurons, whereas astrocytes are generally considered to play supportive
      roles for proper neuronal function. However, accumulating evidence indicates that
      astrocytes sense and control neuronal and synaptic activity, indicating that
      neuron and astrocytes reciprocally communicate. While this evidence has been
      obtained in experimental animal models, whether this bidirectional signaling
      between astrocytes and neurons occurs in human brain remains unknown. We have
      investigated the existence of astrocyte-neuron communication in human brain
      tissue, using electrophysiological and Ca(2+) imaging techniques in slices of the
      cortex and hippocampus obtained from biopsies from epileptic patients. Cortical
      and hippocampal human astrocytes displayed spontaneous Ca(2+) elevations that
      were independent of neuronal activity. Local application of transmitter receptor
      agonists or nerve electrical stimulation transiently elevated Ca(2+) in
      astrocytes, indicating that human astrocytes detect synaptic activity and respond
      to synaptically released neurotransmitters, suggesting the existence of neuron-to
      astrocyte communication in human brain tissue. Electrophysiological recordings in
      neurons revealed the presence of slow inward currents (SICs) mediated by NMDA
      receptor activation. The frequency of SICs increased after local application of
      ATP that elevated astrocyte Ca(2+). Therefore, human astrocytes are able to
      release the gliotransmitter glutamate, which affect neuronal excitability through
      activation of NMDA receptors in neurons. These results reveal the existence of
      reciprocal signaling between neurons and astrocytes in human brain tissue,
      indicating that astrocytes are relevant in human neurophysiology and are involved
      in human brain function.

PMID- 22581851
TI  - Increased cortical and thalamic excitability in freely moving APPswe/PS1dE9 mice
      modeling epileptic activity associated with Alzheimer's disease.
AB  - Amyloid precursor protein transgenic mice modeling Alzheimer's disease display
      frequent occurrence of seizures peaking at an age when amyloid plaques start to
      form in the cortex and hippocampus. We tested the hypothesis that numerous
      reported interactions of amyloid-beta with cell surface molecules result in
      altered excitation-inhibition balance in brain-wide neural networks, eventually
      leading to epileptogenesis. We examined electroencephalograms (EEGs) and auditory
      evoked potentials (AEPs) in freely moving 4-month-old APPswe/PS1dE9 (APdE9) and
      wild-type (WT) control mice in the hippocampus, cerebral cortex, and thalamus
      during movement, quiet waking, non-rapid eye movement sleep, and rapid eye
      movement (REM) sleep. Cortical EEG power was higher in APdE9 mice than in WT mice
      over a broad frequency range (5-100 Hz) and during all 4 behavioral states.
      Thalamic EEG power was also increased but in a narrower range (10-80 Hz).
      Furthermore, APdE9 mice displayed augmented cortical and thalamic AEPs. While
      power and theta-gamma modulation were preserved in the APdE9 hippocampus, REM
      sleep-related phase shift of theta-gamma modulation was altered. Our data suggest
      that at the early stage of amyloid pathology, cortical principal cells become
      hyperexcitable and via extensive cortico-thalamic connection drive thalamic
      cells. Minor hippocampal changes are most likely secondary to abnormal entorhinal
      input.

PMID- 22581853
TI  - Negative feedback regulation of antigen receptors through calmodulin inhibition
      of E2A.
AB  - Signaling from the BCR is used to judge Ag-binding strengths of the Abs of B
      cells. BCR signaling enables the selection for successive improvements in the Ag
      affinity over an extremely broad range of affinities during somatic
      hypermutation. We show that the mouse BCR is subject to general negative feedback
      regulation of the receptor proteins, as well as many coreceptors and proteins in
      signal pathways from the receptor. Thus, the BCR can downregulate itself, which
      can enable sensitive detection of successive improvements in the Ag affinity over
      a very large span of affinities. Furthermore, the feedback inhibition of the BCR
      signalosome and most of its proteins, as well as most other regulations of genes
      by BCR stimulation, is to a large extent through inhibition of the transcription
      factor E2A by Ca(2+)/calmodulin.

PMID- 22581852
TI  - Advance directives in community patients with heart failure.
AB  - BACKGROUND: Although it is recommended that all patients with heart failure (HF)
      have advance directives (AD) in place before the end of life is imminent, the use
      of AD in HF has not been well studied. METHODS AND RESULTS: We enrolled
      consecutive Olmsted County residents presenting with HF from October 2007 through
      October 2011 into a longitudinal study. Information from AD completed before
      enrollment and hospitalizations in the month before death were abstracted. Among
      608 patients (mean age, 74.0 years; 54.9% men; 65.3%; New York Heart Association
      functional class 3 or 4), 164 (27.0%) patients died after a mean follow-up of 1.8
      years. At enrollment, only 249 (41.0%) patients had an AD. Although most AD
      appointed a proxy decision-maker (90.4%), less than half addressed wishes
      regarding use of cardiopulmonary resuscitation (41.4%), mechanical ventilation
      (38.6%), or hemodialysis (10.0%) at the end of life. The independent predictors
      of AD completion were older age (adjusted odds ratio [OR] per 10-year increase,
      1.82; 95% confidence interval [CI], 1.51-2.20), malignancy (OR, 1.58; 95% CI,
      1.05-2.37), and renal dysfunction (OR for estimated glomerular filtration rate
      <60 mL/min 1.55; 95% CI, 1.05-2.29). At the end of life, patients with AD
      specifying limits in the aggressiveness of care less frequently received
      mechanical ventilation (OR, 0.26; 95% CI, 0.07-0.88), with a trend toward
      decreased intensive care unit admission (OR, 0.45; 95% CI, 0.16-1.29).
      CONCLUSIONS: Despite a high mortality rate, over half of patients with HF do not
      have an AD, and existing AD fail to address important end-of-life medical
      decisions.

PMID- 22581854
TI  - Decoy receptor 3 suppresses TLR2-mediated B cell activation by targeting NF
      kappaB.
AB  - Decoy receptor 3 (DcR3) is a soluble protein in the TNFR superfamily. Its known
      ligands include Fas ligand, homologous to lymphotoxin, showing inducible
      expression, and competing with HSV glycoprotein D for herpes virus entry
      mediator, a receptor expressed by T lymphocytes, TNF-like molecule 1A, and
      heparan sulfate proteoglycans. DcR3 has been reported to modulate the functions
      of T cells, dendritic cells, and macrophages; however, its role in regulating B
      cell activation is largely unknown. In this study, we found that the DcR3.Fc
      fusion protein bound to human and mouse B cells and suppressed the activation of
      B cells. DcR3.Fc attenuated Staphylococcus aureus, IgM-, Pam(3)CSK(4)-, and LPS
      mediated B cell proliferation but did not affect cytokine-induced B cell growth.
      In the presence of these mitogens, DcR3.Fc did not induce B cell apoptosis,
      suggesting that DcR3 may inhibit the signal(s) important for B cell activation.
      Because the combination of Fas.Fc, LT-betaR.Fc (homologous to lymphotoxin,
      showing inducible expression, and competing with HSV glycoprotein D for herpes
      virus entry mediator, a receptor expressed by T lymphocytes receptor), and DR3.Fc
      (TNF-like molecule 1A receptor) did not suppress B cell proliferation and because
      the biological effect of DcR3.Fc on B cells was not blocked by heparin, we
      hypothesize that a novel ligand(s) of DcR3 mediates its inhibitory activity on B
      cells. Moreover, we found that TLR2-stimulated NF-kappaB p65 activation and NF
      kappaB-driven luciferase activity were attenuated by DcR3.Fc. The TLR2-induced
      cytokine production by B cells was consistently reduced by DcR3. These results
      imply that DcR3 may regulate B cell activation by suppressing the activation of
      NF-kappaB.

PMID- 22581855
TI  - Leukemia inhibitory factor signaling is required for lung protection during
      pneumonia.
AB  - Lung infections represent a tremendous disease burden and a leading cause of
      acute lung injury. STAT3 signaling is essential for controlling lung injury
      during pneumonia. We previously identified LIF as a prominent STAT3-activating
      cytokine expressed in the airspaces of pneumonic lungs, but its physiological
      significance in this setting has never been explored. To do so, Escherichia coli
      was intratracheally instilled into C57BL/6 mice in the presence of neutralizing
      anti-LIF IgG or control IgG. Anti-LIF completely eliminated lung LIF detection
      and markedly exacerbated lung injury compared with control mice as evidenced by
      airspace albumin content, lung liquid accumulation, and histological analysis.
      Although lung bacteriology was equivalent between groups, bacteremia was more
      prevalent with anti-LIF treatment, suggestive of compromised barrier function
      rather than impaired antibacterial defense as the cause of dissemination.
      Inflammatory cytokine expression was also exaggerated in anti-LIF-treated lungs,
      albeit after injury had ensued. Interestingly, alveolar neutrophil recruitment
      was modestly but significantly reduced compared with control mice despite
      elevated cytokine levels, indicating that inflammatory injury was not a
      consequence of excessive neutrophilic alveolitis. Lastly, the lung transcriptome
      was dramatically remodeled during pneumonia, but far more so following LIF
      neutralization, with gene changes implicating cell death and epithelial
      homeostasis among other processes relevant to tissue injury. From these findings,
      we conclude that endogenous LIF facilitates tissue protection during pneumonia.
      The LIF-STAT3 axis is identified in this study as a critical determinant of lung
      injury with clinical implications for pneumonia patients.

PMID- 22581856
TI  - Kv1.3 deletion biases T cells toward an immunoregulatory phenotype and renders
      mice resistant to autoimmune encephalomyelitis.
AB  - Increasing evidence suggests ion channels have critical functions in the
      differentiation and plasticity of T cells. Kv1.3, a voltage-gated K(+) channel,
      is a functional marker and a pharmacological target for activated effector memory
      T cells. Selective Kv1.3 blockers have been shown to inhibit proliferation and
      cytokine production by human and rat effector memory T cells. We used Kv1.3
      knockout (KO) mice to investigate the mechanism by which Kv1.3 blockade affects
      CD4(+) T cell differentiation during an inflammatory immune-mediated disease.
      Kv1.3 KO animals displayed significantly lower incidence and severity of myelin
      oligodendrocyte glycoprotein (MOG) peptide-induced experimental autoimmune
      encephalomyelitis. Kv1.3 was the only K(V) channel expressed in MOG 35-55
      specific CD4(+) T cell blasts, and no K(V) current was present in MOG-specific
      CD4(+) T cell-blasts from Kv1.3 KO mice. Fewer CD4(+) T cells migrated to the CNS
      in Kv1.3 KO mice following disease induction, and Ag-specific proliferation of
      CD4(+) T cells from these mice was impaired with a corresponding cell-cycle
      delay. Kv1.3 was required for optimal expression of IFN-gamma and IL-17, whereas
      its absence led to increased IL-10 production. Dendritic cells from Kv1.3 KO mice
      fully activated wild-type CD4(+) T cells, indicating a T cell-intrinsic defect in
      Kv1.3 KO mice. The loss of Kv1.3 led to a suppressive phenotype, which may
      contribute to the mechanism by which deletion of Kv1.3 produces an
      immunotherapeutic effect. Skewing of CD4(+) T cell differentiation toward Ag
      specific regulatory T cells by pharmacological blockade or genetic suppression of
      Kv1.3 might be beneficial for therapy of immune-mediated diseases such as
      multiple sclerosis.

PMID- 22581857
TI  - HIV-1 capture and antigen presentation by dendritic cells: enhanced viral capture
      does not correlate with better T cell activation.
AB  - During HIV-1 infection, dendritic cells (DC) facilitate dissemination of HIV-1
      while trying to trigger adaptive antiviral immune responses. We examined whether
      increased HIV-1 capture in DC matured with LPS results in more efficient Ag
      presentation to HIV-1-specific CD4(+) and CD8(+) T cells. To block the DC
      mediated trans-infection of HIV-1 and maximize Ag loading, we also evaluated a
      noninfectious integrase-deficient HIV-1 isolate, HIV(NL4-3DeltaIN). We showed
      that higher viral capture of DC did not guarantee better Ag presentation or T
      cell activation. Greater HIV(NL4-3) uptake by fully LPS-matured DC resulted in
      higher viral transmission to target cells but poorer stimulation of HIV-1
      specific CD4(+) and CD8(+) T cells. Conversely, maturation of DC with LPS during,
      but not before, viral loading enhanced both HLA-I and HLA-II HIV-1-derived Ag
      presentation. In contrast, DC maturation with the clinical-grade mixture
      consisting of IL-1beta, TNF-alpha, IL-6, and PGE(2) during viral uptake only
      stimulated HIV-1-specific CD8(+) T cells. Hence, DC maturation state, activation
      stimulus, and time lag between DC maturation and Ag loading impact HIV-1 capture
      and virus Ag presentation. Our results demonstrate a dissociation between the
      capacity to capture HIV-1 and to present viral Ags. Integrase-deficient HIV(NL4
      3DeltaIN) was also efficiently captured and presented by DC through the HLA-I and
      HLA-II pathways but in the absence of viral dissemination. HIV(NL4-3DeltaIN)
      seems to be an attractive candidate to be explored. These results provide new
      insights into DC biology and have implications in the optimization of DC-based
      immunotherapy against HIV-1 infection.

PMID- 22581858
TI  - IL-15-dependent upregulation of GITR on CD8 memory phenotype T cells in the bone
      marrow relative to spleen and lymph node suggests the bone marrow as a site of
      superior bioavailability of IL-15.
AB  - CD8 memory T cells are enriched in the bone marrow, a site where these cells are
      thought to receive homeostatic signals. However, the primary site where CD8
      memory T cells receive their cytokine-induced homeostatic signals has recently
      come under debate. In this study, we demonstrate that the bone marrow contains a
      fraction of CD8 memory phenotype T cells with elevated expression of
      glucocorticoid-induced TNFR-related protein (GITR). In contrast, splenic and
      lymph node memory phenotype T cells have GITR levels similar to those on naive T
      cells. The bone marrow GITR(hi) memory T cells have a phenotype indicative of
      cytokine activation, with higher CD122 and lower CD127 than do the GITR(basal)
      memory T cells. Remarkably, these bone marrow-specific GITR(hi) cells are almost
      completely ablated in the absence of IL-15, whereas TNFR2 and 4-1BB expression on
      the CD8 memory T cells are IL-15 independent. Furthermore, adoptively transferred
      splenic CD8 memory phenotype T cells show IL-15-dependent GITR upregulation upon
      entry into the bone marrow. This result implies that the selective appearance of
      GITR(hi) memory phenotype T cells in the bone marrow reflects the local
      microenvironment rather than a different subset of memory T cells. GITR(-/-) mice
      have a lower frequency of CD8 memory phenotype cells in the bone marrow, yet the
      GITR(-/-) cells hyperproliferate compared with those in wild-type mice. Taken
      together, these data suggest that GITR plays a role in the survival of CD8 memory
      phenotype T cells and that GITR upregulation represents a precise marker of cells
      that have responded to IL-15.

PMID- 22581859
TI  - EVI1 acts as an inducible negative-feedback regulator of NF-kappaB by inhibiting
      p65 acetylation.
AB  - Inflammation is a hallmark of many important human diseases. Appropriate
      inflammation is critical for host defense; however, an overactive response is
      detrimental to the host. Thus, inflammation must be tightly regulated. The
      molecular mechanisms underlying the tight regulation of inflammation remain
      largely unknown. Ecotropic viral integration site 1 (EVI1), a proto-oncogene and
      zinc finger transcription factor, plays important roles in normal development and
      leukemogenesis. However, its role in regulating NF-kappaB-dependent inflammation
      remains unknown. In this article, we show that EVI1 negatively regulates
      nontypeable Haemophilus influenzae- and TNF-alpha-induced NF-kappaB-dependent
      inflammation in vitro and in vivo. EVI1 directly binds to the NF-kappaB p65
      subunit and inhibits its acetylation at lysine 310, thereby inhibiting its DNA
      binding activity. Moreover, expression of EVI1 itself is induced by nontypeable
      Haemophilus influenzae and TNF-alpha in an NF-kappaB-dependent manner, thereby
      unveiling a novel inducible negative feedback loop to tightly control NF-kappaB
      dependent inflammation. Thus, our study provides important insights into the
      novel role for EVI1 in negatively regulating NF-kappaB-dependent inflammation,
      and it may also shed light on the future development of novel anti-inflammatory
      strategies.

PMID- 22581860
TI  - Contact-dependent interference with invariant NKT cell activation by herpes
      simplex virus-infected cells.
AB  - Invariant CD1d-restricted NKT (iNKT) cells play important roles in generating
      protective immune responses against infections. In this study, we have
      investigated the role of human iNKT cells in HSV-1 infection and their
      interaction with epidermal keratinocytes. These cells express CD1d and are the
      primary target of the virus. Keratinocytes loaded with alpha-galactosyl ceramide
      (alpha-GalCer) could stimulate IFN-gamma production and CD25 upregulation by iNKT
      cells. However, both alpha-GalCer-dependent and cytokine-dependent activation of
      iNKT cells was impaired after coculture with HSV-1-infected cells. Notably, CD1d
      downregulation was not observed on infected keratinocytes, which were also found
      to inhibit TCR-independent iNKT cell activation. Further examination of the
      cytokine profile of iNKT-keratinocyte cocultures showed inhibition of IFN-gamma,
      IL-5, IL-10, IL-13, and IL-17 secretion but upregulation of IL-4 and TNF-alpha
      after the infection. Moreover, cell-to-cell contact between infected
      keratinocytes and iNKT cells was required for the inhibition of activation, as
      the cell-free supernatants containing virus did not affect activation. Productive
      infection of iNKT cells was however not required for the inhibitory effect. After
      coculture with infected cells, iNKT cells were no longer responsive to further
      stimulation with alpha-GalCer-loaded CD1d-expressing cells. We found that
      exposure to HSV-1-infected cells resulted in impaired TCR signaling downstream of
      ZAP70. Additionally, infected cells upregulated the expression of the negative T
      cell regulator, galectin-9; however, blocking experiments indicated that the
      impairment of iNKT cell responses was independent of galectin-9. Thus,
      interference with activation of human iNKT cells by HSV-1 may represent a novel
      immunoevasive strategy used by the virus to avoid immune clearance.

PMID- 22581862
TI  - L-plastin regulates polarization and migration in chemokine-stimulated human T
      lymphocytes.
AB  - Chemokines such as SDF-1alpha play a crucial role in orchestrating T lymphocyte
      polarity and migration via polymerization and reorganization of the F-actin
      cytoskeleton, but the role of actin-associated proteins in this process is not
      well characterized. In this study, we have investigated a role for L-plastin, a
      leukocyte-specific F-actin-bundling protein, in SDF-1alpha-stimulated human T
      lymphocyte polarization and migration. We found that L-plastin colocalized with F
      actin at the leading edge of SDF-1alpha-stimulated T lymphocytes and was also
      phosphorylated at Ser(5), a site that when phosphorylated regulates the ability
      of L-plastin to bundle F-actin. L-plastin phosphorylation was sensitive to
      pharmacological inhibitors of protein kinase C (PKC), and several PKC isoforms
      colocalized with L-plastin at the leading edge of SDF-1alpha-stimulated
      lymphocytes. However, PKC zeta, an established regulator of cell polarity, was
      the only isoform that regulated L-plastin phosphorylation. Knockdown of L-plastin
      expression with small interfering RNAs demonstrated that this protein regulated
      the localization of F-actin at the leading edge of chemokine-stimulated cells and
      was also required for polarization, lamellipodia formation, and chemotaxis.
      Knockdown of L-plastin expression also impaired the Rac1 activation cycle and Akt
      phosphorylation in response to SDF-1alpha stimulation. Furthermore, L-plastin
      also regulated SDF-1alpha-mediated lymphocyte migration on the integrin ligand
      ICAM-1 by influencing velocity and persistence, but in a manner that was
      independent of LFA-1 integrin activation or adhesion. This study, therefore,
      demonstrates an important role for L-plastin and the signaling pathways that
      regulate its phosphorylation in response to chemokines and adds L-plastin to a
      growing list of proteins implicated in T lymphocyte polarity and migration.

PMID- 22581861
TI  - IL-7 functionally segregates the pro-B cell stage by regulating transcription of
      recombination mediators across cell cycle.
AB  - Ag receptor diversity involves the introduction of DNA double-stranded breaks
      during lymphocyte development. To ensure fidelity, cleavage is confined to the
      G(0)-G(1) phase of the cell cycle. One established mechanism of regulation is
      through periodic degradation of the RAG2 recombinase protein. However, there are
      additional levels of protection. In this paper, we show that cyclical changes in
      the IL-7R signaling pathway functionally segregate pro-B cells according to cell
      cycle status. In consequence, the level of a downstream effector of IL-7
      signaling, phospho-STAT5, is inversely correlated with cell cycle expression of
      Rag, a key gene involved in recombination. Higher levels of phopho-STAT5 in S
      G(2) correlate with decreased Rag expression and Rag relocalization to
      pericentromeric heterochromatin. These cyclical changes in transcription and
      locus repositioning are ablated upon transformation with v-Abl, which renders
      STAT5 constitutively active across the cell cycle. We propose that this activity
      of the IL-7R/STAT5 pathway plays a critical protective role in development,
      complementing regulation of RAG2 at the protein level, to ensure that
      recombination does not occur during replication. Our data, suggesting that pro-B
      cells are not a single homogeneous population, explain inconsistencies in the
      role of IL-7 signaling in regulating Igh recombination.

PMID- 22581863
TI  - CIKS/Act1-mediated signaling by IL-17 cytokines in context: implications for how
      a CIKS gene variant may predispose to psoriasis.
AB  - Psoriasis is a relapsing skin disease characterized by abnormal keratinocyte
      proliferation and differentiation and by an influx of inflammatory immune cells.
      Recently, IL-17 cytokines have been strongly implicated as critical for the
      pathogenesis of this disease. IL-17A (also known as IL-17) and IL-17F are the
      signature cytokines of Th17 cells, but are also produced by innate cells,
      including gammadelta T cells present in skin, whereas epithelial cells, including
      keratinocytes, may produce IL-17C. IL-17 cytokines signal via the adaptor protein
      connection to IkappaB kinase and stress-activated protein kinases (CIKS)/Act1.
      Psoriasis is a disease with a strong genetic predisposition, and the gene
      encoding CIKS has recently been identified as a susceptibility locus.
      Unexpectedly, one predisposing gene variant features a mutation that impairs
      rather than enhances CIKS-mediated IL-17 cytokine signaling, counter to the
      predicted role for IL-17 cytokines in psoriatic inflammation. In this study, we
      demonstrate, however, that this mutant adaptor does not impair the IL-17-specific
      contributions to the genetic response when combined with TNF-alpha, a cytokine
      also prominent in psoriatic inflammation. Interestingly, TNF-alpha signals
      compensate IL-17 signaling defects imposed by this mutant adaptor even for genes
      that are not induced by TNF-alpha alone, including the transcription factors
      CCAAT/enhancer binding protein delta and IkappaBzeta, which help regulate
      secondary gene expression in response to IL-17. Based on these findings we
      discuss a scenario in which the mutant adaptor may interfere with homeostatic
      maintenance of epithelial barriers, thereby potentially enabling the initiation
      of inflammatory responses to insults, whereas this same mutant adaptor would
      still be able to mediate IL-17-specific contributions to inflammation once TNF
      alpha is present.

PMID- 22581864
TI  - Is radiofrequency ablation more effective than stereotactic ablative radiotherapy
      in patients with early stage medically inoperable non-small cell lung cancer?
AB  - A best evidence topic in thoracic surgery was written according to a structured
      protocol. The question addressed was 'is radiofrequency ablation more effective
      than stereotactic ablative radiotherapy in patients with early stage medically
      inoperable non-small cell lung cancer?' Altogether, over 219 papers were found,
      of which 16 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. Radiofrequency
      ablation (RFA) and stereotactic ablative radiotherapy (SABR) offer a clear
      survival benefit compared with conventional radiotherapy in the treatment of
      early stage non-small cell lung cancer (NSCLC) in medically inoperable patients.
      Overall survival at 1 year (68.2-95% vs. 81-85.7%) and 3 years (36-87.5% vs. 42.7
      56%) was similar between patients treated with RFA and SABR. However, 5-year
      survival was higher in SABR (47%) than RFA (20.1-27%). Local progression rates
      were lower in patients treated with SABR (3.5-14.5% vs. 23.7-43%). Both
      treatments were associated with complications. Pneumothorax (19.1-63%) was the
      most common complication following RFA. Fatigue (31-32.6%), pneumonitis (2.1
      12.5%) and chest wall pain (3.1-12%) were common following SABR. Although tumours
      <= 5 cm in size can be effectively treated with RFA, results are better for
      tumours <= 3 cm. One study documented increased recurrence rates with larger
      tumours and advanced disease stage following RFA. Another study found increasing
      age, tumour size, previous systemic chemotherapy, previous external beam
      radiotherapy and emphysema increased the risk of toxicity following SABR and
      suggested that risk factors should be used to stratify patients. RFA can be
      performed in one session, whereas SABR is more effective if larger doses of
      radiation are given over two to three fractions. RFA is not recommended for
      centrally based tumours. Patients with small apical tumours, posteriorly
      positioned tumours, peripheral tumours and tumours close to the scapula where it
      may be difficult to position an active electrode are more optimally treated with
      SABR. Treatment for early stage inoperable NSCLC should be tailored to individual
      patients, and under certain circumstances, a combined approach may be beneficial.

PMID- 22581865
TI  - Primary cardiac diffuse large B-cell lymphoma, non-germinal centre B-cell type in
      an immunocompetent woman.
AB  - Primary cardiac lymphomas are extremely rare and always occur in immunodeficient
      persons. Here, we report a very rare case of a primary cardiac diffuse large B
      cell lymphoma in an immunocompetent 41-year old woman. Echocardiography and
      computed tomography revealed a mass measuring 74 mm 49 mm in the right atrium. No
      tumour formations were recognized in other organs. Laboratory data did not reveal
      immunosuppression, and the human immunodeficiency virus was negative.
      Histological and immunohistochemical studies showed that the cardiac tumour was
      diffuse large B-cell lymphoma, non-germinal centre B-cell type. Epstein-Barr
      Virus-encoded small RNA was negative by in situ hybridization. The patient died 6
      months after the operation.

PMID- 22581866
TI  - Biological basis for the protective effect conferred by male circumcision against
      HIV infection.
AB  - Here we provide an up-to-date review of research that explains why uncircumcised
      men are at higher risk of HIV infection. The inner foreskin is a mucosal
      epithelium deficient in protective keratin, yet rich in HIV target cells. Soon
      after sexual exposure to infected mucosal secretions of a HIV-positive partner,
      infected T-cells from the latter form viral synapses with keratinocytes and
      transfer HIV to Langerhans cells via dendrites that extend to just under the
      surface of the inner foreskin. The Langerhans cells with internalized HIV migrate
      to the basal epidermis and then pass HIV on to T-cells, thus leading to the
      systemic infection that ensues. Infection is exacerbated in inflammatory states
      associated with balanoposthitis, the presence of smegma and ulceration -
      including that caused by infection with herpes simplex virus type 2 and some
      other sexually transmitted infections (STIs). A high foreskin surface area and
      tearing of the foreskin or associated frenulum during sexual intercourse also
      facilitate HIV entry. Thus, by various means, the foreskin is the primary
      biological weak point that permits HIV infection during heterosexual intercourse.
      The biological findings could explain why male circumcision protects against HIV
      infection.

PMID- 22581867
TI  - Assessing adherence in Thai patients taking combination antiretroviral therapy.
AB  - In settings where medications and viral load (VL) monitoring are limited by cost,
      clinicians need reliable ways to assess patient adherence to therapy. We assessed
      sensitivity and specificity of two self-reported adherence tools (a visual
      analogue scale [VAS] and the CASE [Center for Adherence Support Evaluation]
      adherence index), against a standard of detectable VL, with 288 patients from
      three sites in Thailand. We also assessed predictors of non-adherence. The
      sensitivity and specificity of the VAS <95% and CASE adherence index <=11 against
      a VL >50 copies/mL were 26% and 90%, 19% and 95%, respectively. Against a VL
      >=1000 copies/mL sensitivities increased to 55% and 36%, respectively, and
      specificities were unchanged. Attending a clinic not staffed by HIV specialists
      (odds ratio [OR] 3.14; 95% confidence interval [CI] 1.19-8.34) and being educated
      to primary school level or less (OR 2.24; 95% CI 1.01-4.94) were associated with
      self-reported adherence <95% on the VAS in multivariate analysis. Adherence
      assessed by the VAS was a more accurate predictor of detectable VL. Policy-makers
      in resource-limited settings should ensure that treatment centres are staffed
      with well-trained personnel aware of the importance of good patient adherence.

PMID- 22581868
TI  - Identification of potential drug-drug interactions between antiretroviral drugs
      from prescriptions in the private health-care sector in South Africa.
AB  - The aim of this study was to identify potential drug-drug interactions (DDIs)
      between antiretroviral drugs (ARVs) and to determine whether prescribed daily
      doses (PDDs) from prescriptions can be used in the evaluation of these
      interactions. A quantitative, retrospective drug utilization study was performed
      on 49,995 and 81,096 ARV prescriptions from a South African pharmacy benefit
      management company, which were prescribed to 7664 and 10,162 HIV patients for
      2005 and 2006, respectively. Potential DDIs identified across different age
      groups were 778 for 2005 and 1155 for 2006; the majority occurred in patients
      aged 19 to <=45 years. The potential DDIs identified between ARVs were all
      interacting at clinical significance level 2 according to guidelines indicated by
      Tatro. These results demonstrate that potential DDIs were identified between ARVs
      mostly in three ARV combinations: Kaletra((r)) (lopinavir/ritonavir) and
      efavirenz, lopinavir/ritonavir and nevirapine and combinations of indinavir and
      ritonavir. There is a need for more education on the prescribing protocols for
      ARVs in the treatment of HIV-infected patients in the private health-care sector
      in South Africa.

PMID- 22581869
TI  - Adolescents' agreement to test for HIV when different testing methods are
      offered.
AB  - Offering rapid HIV testing improves rates of testing in adults, but little is
      known about whether offering adolescents a choice of testing methods increases
      rates of testing. The aims of the study were to determine rates of HIV testing in
      adolescents when different testing methods were offered and explore factors
      associated with agreement to be tested for HIV. Participants (n= 200, sexually
      experienced 13-22 year olds) were recruited from an urban adolescent clinic,
      completed a 99-item theory-based survey and were offered their choice of
      venipuncture, rapid fingerstick or rapid oral fluid HIV testing. Approximately
      half (49.5%) agreed to HIV testing. Male gender, parental completion of high
      school, intention to test for HIV if offered by clinician and higher perceived
      likelihood of current HIV infection were independently associated with agreement
      to test. Combining new strategies, such as opt-out testing, with routine testing
      may be needed to improve rates of adolescent HIV testing.

PMID- 22581870
TI  - Persons at high risk for HIV infection in Kisumu, Kenya: identifying recruitment
      strategies for enrolment in HIV-prevention studies.
AB  - A combination of in-depth interviews (n = 38) and surveys (n = 203) were used to
      (1) identify strategies to recruit persons at high risk for HIV infection; (2)
      determine whether one strategy was more successful than others; and (3) describe
      motivators and barriers to participation in HIV-prevention studies. From in-depth
      interviews, four main recruitment strategies were identified: (1) use of a person
      with specific knowledge of a target population (link person mobilization); (2)
      use of co-workers or contemporaries (peer mobilization); (3) use of group or
      association leaders (leader mobilization); and (4) contacting persons by study
      staff directly (staff contact mobilization). The odds of inconsistently using
      condoms during sex were greater among those recruited using the peer mobilization
      (adjusted odds ratio [AOR] = 3.59; 95% confidence interval [CI] = 1.35-9.54) and
      the leader mobilization strategies (AOR = 2.76; 95% CI = 1.04-7.38) compared with
      the link person mobilization strategy. The main motivators for taking part in an
      HIV research study were receiving HIV-prevention education, HIV information or
      counselling, and receiving compensation for study participation. The main
      barriers were fear of lack of confidentiality and HIV testing concerns. Using
      evaluated strategies to recruit persons at high risk for HIV infection and
      addressing barriers to participation will improve the conduct and outcome of HIV
      prevention studies.

PMID- 22581872
TI  - Human papillomavirus in the oral cavity of children and mode of delivery: a
      retrospective study.
AB  - Our study aimed to examine the relationship between the presence of human
      papillomavirus (HPV) in the oral cavity of children and their mode of delivery.
      We investigated the presence of HPV infection in oral biopsies from 190 children
      (mean age: 7 years, range: 2-14 years) using the polymerase chain reaction (PCR)
      technique. Sixteen of 190 children (8.4%) were HPV-positive, with no significant
      difference between those delivered vaginally and by Caesarean section (C
      section). The majority of the HPV-positive children were infected with type 16,
      whereas in the younger age group HPV type 11 was detected more frequently in
      children delivered by normal vaginal delivery (NVD) than by C-section. Our
      findings demonstrate the presence of HPV in the oral cavity of children delivered
      by both C-section as well as NVD. Further research on the possible modes of
      transmission of oral HPV infection will enable us to understand the natural
      history of HPV infection in childhood.

PMID- 22581871
TI  - Implementing bathhouse-based voluntary counselling and testing has no adverse
      effect on bathhouse patronage among men who have sex with men.
AB  - Implementing HIV voluntary counselling and testing (VCT) in bathhouses is a
      proven public health strategy for reaching high-risk men who have sex with men
      (MSM) and efficiently identifying new HIV cases. However, some bathhouse managers
      are concerned that VCT programmes could adversely affect business. This study
      examined whether offering VCT on the premises of a bathhouse changed patterns of
      patron visits. A collaborating bathhouse provided electronic anonymized patron
      data from their entire population of attendees. VCT was offered on premises with
      varying frequencies over the course of three years. Club entrances and exits were
      modelled as a function of intensity of VCT programming. Club entrances did not
      differ as a function of how many days per week testing was being offered in a
      given month. Additionally, club entrances did not decrease, nor did club exits
      increase, during specific half-hour time periods when testing was offered.
      Implementing bathhouse-based VCT did not have any demonstrable impact on
      patronage. Public health officials can leverage these results to help alleviate
      club managers' concerns about patron reactions to providing testing on site, and
      to support expanding sexual health programmes for MSM in these venues.

PMID- 22581873
TI  - The cost of managing genital warts in the UK.
AB  - The national cost of managing genital warts (GWs) in the UK has not been fully
      estimated, yet is required to inform decisions on vaccination against human
      papillomavirus. This study estimated the 2010 UK costs based on secondary
      genitourinary (GU) medicine clinic data from the Health Protection Agency (HPA)
      and primary care data from the Health Improvement Network database. Extrapolating
      data to 2010 resulted in 173,077 GU medicine clinic and 16,782 primary care GW
      episodes. Using treatment patterns obtained from key opinion leaders and tariffs
      from National Health Service Payment by Results (NHS PbR), the national costs
      were estimated at L52.4 million: L276 per treated GW episode.

PMID- 22581874
TI  - Anal human papillomavirus infection in a street-based sample of drug using HIV
      positive men.
AB  - HIV facilitates an increase in human papillomavirus (HPV)-associated conditions.
      HIV-positive men living in a substance use context in Los Angeles, USA, were
      recruited using respondent-driven sampling, completed a questionnaire and had
      biological samples including an anal HPV swab taken. A total of 316 evaluable men
      were enrolled in the study. The prevalence of any HPV, high-risk (HR) infection
      and multiple-type infection was highest for men who have sex with men (MSM)
      (93.9%, 64.6% and 29.7%, respectively). When any HPV and HR-HPV prevalence in all
      men was stratified by age, the youngest group had 100% and 68.2% prevalence,
      respectively, with similarly high rates maintained up to age 49 years. The
      individual's use of alcohol, marijuana, cocaine, methamphetamine or heroin was
      not significantly associated with anal HPV detection. In this marginalized
      population, high prevalence rates of anal HPV and HR-HPV occurring over a wide
      age range may increase the individual's risk for anal dysplasia and anal cancer.

PMID- 22581876
TI  - UK national re-audit of sexual history-taking.
AB  - A focused repeat national audit of sexual history-taking was conducted in
      genitourinary (GU) medicine clinics in the UK in 2010, addressing several areas
      of practice under-performance identified in the baseline 2008 national audit. The
      case-notes of 4285 patients were audited. An increase in documentation was
      observed for all measures, except legibility which was unchanged. Despite the
      overall improvement, several measures (chaperone offer, condom usage and four of
      five aspects of HIV risk assessment) remained below target.

PMID- 22581875
TI  - Are there benefits to starting antiretroviral therapy during primary HIV
      infection? Conclusions from the Seattle Primary Infection Cohort vary by control
      group.
AB  - It is controversial whether starting combination antiretroviral therapy (cART)
      during primary HIV infection (PHI) is beneficial. Subjects in this observational
      cohort began cART <30 days (group 1: acute treatment, n = 40), 31-180 days (group
      2: early treatment, n = 82) or >180 days (group 3: delayed treatment, n = 35)
      after HIV infection, and were compared with 27 historical and 60 contemporary
      controls. Time to HIV-related diagnoses did not differ for group 1 (adjusted
      hazard ratio [aHR] 1.44, P = 0.3) or group 2 (aHR 1.17, P = 0.5) compared with
      contemporary controls, but it was delayed for both treated groups (aHR 0.38 for
      group 1, P = 0.01; and aHR 0.28 for group 2, P < 0.0001) compared with historical
      controls. Although rates of HIV-related diagnoses were similar in acutely treated
      subjects and contemporary controls, results were confounded by associations
      between higher CD4 counts, lower HIV RNA levels and delayed disease progression
      as reasons for deferring treatment. Randomized trials are needed to address
      benefits of cART during PHI.

PMID- 22581877
TI  - Sulphadiazine-induced obstructive renal failure complicating treatment of HIV
      associated toxoplasmosis.
AB  - A patient with newly-diagnosed HIV infection and biopsy-proven cerebral
      toxoplasmosis was treated with sulphadiazine and pyrimethamine. Despite adequate
      hydration and daily examination of urine for sulphadiazine crystals obstructive
      uropathy due to bilateral ureteric stones with hydronephrosis occurred, resulting
      in rapid onset renal failure. Sulphadiazine was discontinued and clindamycin was
      substituted. With intravenous fluid hydration and bilateral nephrostomies the
      urolithiasis resolved. This case serves to remind clinicians of the need for
      vigilance when treating cerebral toxoplasmosis with sulphadiazine, in order to
      avoid this potentially serious complication of treatment.

PMID- 22581878
TI  - Transient bone marrow oedema syndrome in an HIV-infected patient on highly active
      antiretroviral therapy.
AB  - Bone marrow oedema syndrome (BMES, also known as transient osteoporosis) is an
      uncommon, self-limiting condition characterized by disabling pain, reversible
      osteopaenia on X-rays and by bone marrow oedema pattern on magnetic resonance
      imaging (MRI). Here we describe the first reported case of BMES in an HIV
      positive patient on highly active antiretroviral therapy.

PMID- 22581879
TI  - Nodal cryptococcal immune reconstitution inflammatory syndrome masquerading as
      tuberculosis in an HIV-infected patient.
AB  - An African HIV-infected patient presented with widespread necrotic
      lymphadenopathy five months after starting combination antiretroviral therapy
      (cART) and was thought to have disseminated tuberculosis in the context of an
      immune reconstitution inflammatory syndrome (IRIS) on the basis of typical
      imaging appearances and suggestive appearances from a fine needle aspirate of a
      nodal mass. The patient deteriorated despite empirical antituberculosis therapy
      and the correct diagnosis of nodal cryptococcal infection was subsequently
      established by histological examination of a core biopsy from a lymph node. IRIS
      should be borne in mind when considering the differential diagnosis in a patient
      who has recently started cART.

PMID- 22581880
TI  - Complicated lymphogranuloma venereum infection mimicking deep vein thrombosis in
      an HIV-positive man.
AB  - A 41-year-old HIV-positive man who has sex with men (MSM) with a family history
      of deep vein thrombosis (DVT) presented to the emergency department with an
      acutely swollen lower limb. The initial clinical diagnosis was of a possible DVT
      and the patient was anticoagulated. However, investigations subsequently excluded
      DVT and sexually acquired reactive arthropathy (SARA) was eventually diagnosed.
      This complication followed an earlier attendance at the emergency department,
      where proctitis due to lymphogranuloma venereum (LGV) infection went
      unrecognized. This is the first reported case of LGV infection mimicking a DVT.
      Prompt recognition and treatment of the initial proctitis may have prevented the
      development of SARA.

PMID- 22581881
TI  - AIDS-associated Kaposi's sarcoma of the conjunctiva in a woman.
AB  - Conjunctival involvement by AIDS-associated Kaposi's sarcoma (KS) is rare, more
      so in women. We present a case of a 34-year-old African-American woman with AIDS,
      who was admitted to our hospital and diagnosed with KS of the conjunctiva. To
      date there are only a few reported cases of AIDS-associated conjunctival KS in
      the literature. This case is the first case of AIDS-associated conjunctival KS in
      an African-American woman and emphasizes the importance of considering KS as a
      differential diagnosis of the conjunctival mass in HIV-positive patients.

PMID- 22581882
TI  - HIV-positive mothers attending an HIV clinic in south Wales.

PMID- 22581883
TI  - Untreated Trichomonas vaginalis for 20 years: lessons to be learnt?

PMID- 22581884
TI  - Testing the children of HIV-positive mothers.

PMID- 22581885
TI  - Three-year evaluation of neuropsychiatric adverse events in the MONET trial of
      darunavir/ritonavir, with or without nucleoside analogues.

PMID- 22581886
TI  - Do not forget schistosomiasis: a rare cause of changes in ejaculate.

PMID- 22581887
TI  - Cervical cytology screening in HIV-positive women: do samples from genitourinary
      medicine departments have high inadequacy rates?

PMID- 22581888
TI  - Human papillomavirus infections in women with clinical gynaecological diseases in
      southwest China.
AB  - The aim of this study was to determine the prevalence of human papillomavirus
      (HPV) infections in women with different gynaecological diseases (GDs) and ages
      in southwest China. With the assay of reverse dot blot, a total of 5544 cervical
      samples, including 1008 normal and 4536 abnormal specimens from women with GDs,
      were assayed for HPV detection. For the normal group, 20.2% (204/1008) tested
      positive for HPV, of which 40.2% (82/204) were high-risk (HR-HPV) genotypes. In
      the 4536 abnormal samples, 1569 women (34.6%) tested positive for HPV: 73.5%
      (1153/1569) had a single infection, 17.7% (277/1569) dual infection and 8.8%
      (138/1569) multiple HPV infection. Of 1569 HPV-positive specimens, 58.7%
      (921/1569) were infected with only HR-HPV genotypes. Significant differences in
      HPV infections were found among women of different ages (P < 0.01), number of
      pregnancies (P < 0.01), GDs (P < 0.01) and age at first sex (P < 0.01). In the
      present study, we found a high prevalence of HPV infection in women with GDs in
      southwest China. In addition to HPV types 16 and 18, a significant proportion of
      other HR-HPV genotypes were detected in this population.

PMID- 22581889
TI  - Assessment of non-marital sexual behaviours of men in Bangladesh: a
      methodological experiment using a modified confidential ballot-box method.
AB  - This study assessed the effectiveness of a modified ballot-box method (MBBM) in
      eliciting non-marital sexual behaviours compared with face-to-face interview
      (FTFI). A cross-sectional survey collected data from men aged 18-49 years in
      Bangladesh using a multistage cluster sampling method. In total, 3499 and 3623
      respondents were interviewed by MBBM and FTFI, respectively. In the MBBM, pre
      recorded questions were administered using a portable audio-cassette player with
      two pairs of headphones used concurrently by the respondent and the interviewer.
      Overall, 18% of the respondents had non-marital sexual exposure in the past year.
      The MBBM elicited higher responses of non-marital sex (adjusted odds ratio (aOR)
      1.3, 95% confidence interval [CI]: 1.1, 1.5) compared with FTFI. The interview
      methods did not, however, revealed significant differences in response to condom
      use rates and the number of non-marital sexual partners. The MBBM is more
      effective than the FTFI method in eliciting higher responses rates of non-marital
      sexual contacts and may be recommended for reliable estimates of sexual
      behaviours.

PMID- 22581890
TI  - Long-term efficacy and safety of once-daily fosamprenavir 1400 mg boosted by
      ritonavir 100 mg: the BOLD100 study.
AB  - In a retrospective database study at two HIV treatment centres, medical records
      were accessed to evaluate long-term efficacy and safety parameters in all HIV
      infected adults who had achieved HIV-1 RNA <50 copies/mL following the initiation
      of fosamprenavir (FPV)/ritonavir (RTV) 1400 mg/100 mg once-daily (QD)-containing
      regimens between January 2004 and January 2006. Data were available for 20
      antiretroviral (ARV)-naive patients (baseline median HIV-1 RNA 5.0 log(10)
      copies/mL; CD4+ cell count 307 cells/mm(3)), 30 protease inhibitor (PI)-naive,
      ARV-experienced patients (HIV-1 RNA 3.6 log(10) copies/mL; CD4+ count 348
      cells/mm(3)) and 25 PI-experienced patients switching to FPV/RTV100 for reasons
      other than virological failure (HIV-1 RNA 2.7 log(10) copies/mL; CD4+ count 328
      cells/mm(3)). HIV-1 RNA <50 copies/mL was achieved in 100% of the ARV-naive
      cohort (median monitoring period, 2.4 years; range, 1.4-3.2 years), 87% of the PI
      naive cohort (2.4 years; range, 1.2-3.4 years) and 88% of the PI-experienced
      cohort (2.2 years; range, 1.0-3.2 years). Virological failure occurred in 0%, 7%
      and 8% of the cohorts, respectively, and median CD4+ count increased above
      baseline by 224, 155 and 115 cells/mm(3), respectively. Change from baseline in
      median fasting lipids was: total cholesterol +12, -6, -2 mg/dL; low-density
      lipoprotein-cholesterol 0, -5, +12 mg/dL; high-density lipoprotein-cholesterol
      +4, +2, +7 mg/dL; triglycerides +9, -21, -65 mg/dL, respectively. In conclusion,
      FPV/RTV 1400/100 mg QD-containing regimens remained effective long-term in all
      ARV-naive and most PI-naive and PI-experienced HIV-infected patients.

PMID- 22581891
TI  - Condom use, intervention service utilization and HIV knowledge among female sex
      workers in China: results of three consecutive cross-sectional surveys in
      Shandong Province with historically low HIV prevalence.
AB  - Heterosexual transmission of HIV through contact with female sex workers (FSWs)
      is a growing concern for the HIV/AIDS epidemic in China. Using consecutive cross
      sectional surveys, we examined the prevalence of HIV and sexually transmitted
      infections (STIs), risk behaviours, HIV knowledge and the utilization of
      intervention services among FSWs in Shandong Province. Of 3460 participants, half
      reported ever having STI-related symptoms, 57.8% had >=7 clients in the last
      week, half reported inconsistent use of condoms with clients and 11.2% reported
      ever using illicit drugs. Consistent use of condoms with clients was associated
      with higher education, being 20-24 years of age, being recruited from hotels,
      having ever received free condoms and was inversely associated with STI-related
      symptoms. HIV-related knowledge was associated with higher education, ever
      testing for HIV and inversely associated with self-reported STI-related symptoms.
      The low rates of condom use, high number and frequent turnover of clients, high
      prevalence of self-reported STIs and drug use highlight the urgency for more
      effective intervention in these FSWs.

PMID- 22581892
TI  - Management of Neisseria gonorrhoeae infection over 12 months in a genitourinary
      medicine setting against British Association for Sexual Health and HIV auditable
      outcome measures.
AB  - Audit of gonorrhoea management resulted in recognition of a need to change the
      clinic protocol for first-line antibiotic therapy and also in improvements in
      clinic recording of written information given to patients and the outcome of
      contact tracing.

PMID- 22581893
TI  - Upper gastrointestinal bleeding in a young female with AIDS: a case report.
AB  - Upper gastrointestinal haemorrhage (UGIH) is a surprisingly common condition in
      patients with AIDS (PWAs), affecting at least 6%. With the growing number of PWAs
      and their increasing life span, UGIH will certainly gain importance as a
      diagnostic and therapeutic challenge to health-care professionals, especially in
      central and eastern Europe because of the AIDS epidemics rapidly developing in
      that region. With the scarcity of reported cases, lack of management guidelines
      of UGIH in PWAs, and limited therapeutic possibilities in developing countries,
      important therapeutic problems should be anticipated. We present a case of UGIH
      in a female PWA due to ketoprofen overuse, successfully managed with conservative
      treatment.

PMID- 22581894
TI  - Atypical progressive multifocal leukoencephalopathy in HIV with a high CD4 count:
      the use of magnetic resonance imaging plus spectrometry studies.
AB  - Progressive multifocal leukoencephalopathy (PML) is still a underinvestigated
      central nervous system infection, often linked to HIV-related immunodeficiency.
      We present an unusual case report characterized by motor involvement, which
      occurred as the first AIDS-defining event in the absence of appreciable
      immunodeficiency in a patient with previously undiagnosed HIV infection, who was
      also assessed by a functional-metabolic magnetic resonance imaging technique (MRI
      spectrometry). A 45-year-old patient had HIV infection detected after the
      appearance of motor abnormalities, in the absence of other signs or symptoms. No
      significant immunodeficiency was found (initial CD4+ lymphocyte count of 566
      cells/uL), and HIV viral load was 24,000 RNA copies/mL. Combination
      antiretroviral therapy was started with lamivudine, abacavir and
      lopinavir/ritonavir, with subsequent addition of efavirenz and enfuvirtide.
      Elevated cerebrospinal fluid levels of JC virus (JCV) (11,668 copies/uL) and
      consistent neuroradiological findings at contrast-enhanced computed tomography
      and MRI scans confirmed a diagnosis of PML. Despite the aggressive therapeutic
      approach, which achieved undetectable HIV viraemia, a CD4+ count above 700
      cells/uL and disappearance of JCV after 20 days, the neurological motor
      involvement rapidly deteriorated, yet associated cognitive impairment never
      occurred. Clinical and neuroradiological deterioration occurred, and our patient
      died five months after the diagnosis due to respiratory failure. Combined MRI
      spectrometry studies performed 10 days before death included proton ((1)H)
      spectrometry, and an MRI study-calculation of water diffusion and anisotropy:
      through this innovative technique combining morphological and metabolic findings,
      multiple abnormalities involving the subtentorial white matter were detected
      (with multiple encephalic trunk and ponto-bulbar lesions), which usually are not
      part of the PML course.

PMID- 22581895
TI  - Acute gonococcal Fitz-Hugh-Curtis syndrome: a case report.
AB  - A case of acute Fitz-Hugh-Curtis syndrome in a young woman with purulent
      peritonitis and acute purulent appendicitis and oophoritis is presented. Open
      emergency appendectomy was performed and peritoneal pus was drained. Neisseria
      gonorrhoeae was cultured from the peritoneal pus. The hepatic enzymes were found
      to be raised. The patient was successfully managed and is asymptomatic after
      three months follow-up. To our knowledge, this is the first case of Fitz-Hugh
      Curtis syndrome reported from Kuwait.

PMID- 22581896
TI  - Development of primary central nervous system lymphoma in an HIV-infected patient
      after multiple opportunistic infections.
AB  - A 35-year-old Chinese man presented to medical attention with fever, cough and
      shortness of breath and HIV infection. His CD4+ lymphocyte count was 28 cells/MUL
      and his HIV viral load was 386,891 copies/mL. Diagnosis of tuberculosis,
      Pneumocystis jiroveci pneumonia, mycobacterium avium complex, fungal infection
      and cytomegalovirus retinitis were confirmed according to the symptoms,
      laboratory results and radiology. After therapy for all these opportunistic
      infections, his symptoms were relieved. In addition, highly active antiretroviral
      therapy (HAART) was also initiated two weeks after his admission. The patient had
      a headache two months after admission and the magnetic resonance image of the
      brain showed left frontal lobe hypodensity. The patient then accepted brain
      biopsy and the pathological result proved to be primary central nervous system
      lymphoma). The patient refused further therapy and lost in our follow-up.

PMID- 22581897
TI  - Long-term stabilized immunological-virological parameters of HIV infection in an
      AIDS presenter followed for 20 years, with irregular or no antiretroviral
      therapy.
AB  - We report the case of an HIV-infected patient who has been followed for 20 years,
      and despite presenting with AIDS (due to three episodes of cryptococcosis plus
      one of Pneumocystis jirovecii pneumonia) who during subsequent years missed,
      refused or took with limited compliance all recommended medications, including
      combination antiretroviral therapy, and primary and secondary antimicrobial
      chemoprophylaxis against opportunistic infections. The unexpected clinical and
      laboratory stabilization of our patient paralleled a progressive increase in his
      peripheral CD4+ T-lymphocyte count (range 410-825 cells/mL) and a relatively
      controlled HIV viraemia (5970-44,000 HIV-RNA copies/mL). Such a recovery of
      sufficient immune competency after experiencing four episodes of severe AIDS
      associated opportunistic infections, without reliable antiretroviral and
      antimicrobial support raises several questions.

PMID- 22581898
TI  - Spontaneous clearance of chronic hepatitis C infection in a patient with a 20
      year-old HIV-hepatitis C co-infection and chronic active hepatitis.
AB  - We report a case of spontaneous clearance of hepatitis C virus (HCV) in a patient
      co-infected for 20 years with HCV and HIV, and with an chronic active hepatitis C
      never treated with anti-HCV regimens. We review the literature of eight anecdotal
      reports describing the spontaneous resolution of chronic HCV infection among HIV
      infected patients, and discuss the virological, immunological, pathogenetic and
      therapeutic implications of this observation.

PMID- 22581899
TI  - Detection of the Treponema pallidum gene and variation of treponemal DNA load
      before and after therapy.
AB  - We explored a genetic detection method for Treponema pallidum (TP) in the
      peripheral blood of infected patients to compare the loads of treponemal DNA
      before and after therapy and to see if this new technique enabled assessment of
      therapeutic effect and detection of serum resistance. Polymerase chain reaction
      was used for a qualitative detection of TP DNA in peripheral blood and then a
      semiquantitative method was adopted to estimate the load of TP DNA in blood, both
      before and after treatment of syphilis. Among 30 untreated patients, three cases
      were TP DNA-positive. Among 42 treated patients with demonstrated serum
      resistance, three cases were TP DNA-positive. Five cases in which the rapid
      plasma reagin had become negative had no detectable TP DNA in their peripheral
      blood. The TP DNA load in blood after treatment was significantly lower than that
      before therapy. We conclude that the detection of TP DNA in peripheral blood of
      TP-infected patients is not yet sufficiently sensitive, but we observed that TP
      DNA load declines significantly after treatment.

PMID- 22581900
TI  - Study of HIV/AIDS-related knowledge among junior high-school students in
      Shanghai, China.
AB  - The aim of this study was to assess the HIV/AIDS-related knowledge among junior
      high-school students in Shanghai, China, and the factors influencing this
      knowledge. A cross-sectional study was conducted in 20 middle schools of two
      districts by a cluster-stratified selection procedure in Shanghai, China. The
      2432 sampled students, aged from 11.1 to 16.7 years, completed a self
      administered questionnaire of HIV/AIDS prevention. The results showed that the
      overall correct rate of HIV/AIDS-related knowledge was 62%. Using multivariable
      logistic regression analysis, we found that the main factors influencing HIV/AIDS
      related knowledge among junior high school students were the type of school (odds
      ratio [OR] = 1.641), age (OR = 1.727), whether the student was a single child in
      the family (OR = 1.389), whether the student had previous HIV/AIDS-related
      education experience (OR = 2.003) and whether the student had ever discussed
      HIV/AIDS with their parents (OR = 1.282). The results indicate that HIV/AIDS
      related knowledge among Shanghai junior high school students is not high enough,
      and more attention needs to be paid to enhance HIV/AIDS-related knowledge,
      especially among younger students from common type schools without HIV/AIDS
      related education experience. We encourage Chinese parents to get involved in
      their children's HIV/AIDS prevention education.

PMID- 22581901
TI  - Desulfatitalea tepidiphila gen. nov., sp. nov., a sulfate-reducing bacterium
      isolated from tidal flat sediment.
AB  - A novel sulfate-reducing bacterium, strain S28bF(T), was isolated from tidal flat
      sediment from Tokyo Bay, Japan. Cells of strain S28bF(T) were rod-shaped (0.5
      0.6*1.7-3.8 um), motile and Gram-stain-negative. For growth, the optimum pH was
      pH 6.8-7.3 and the optimum temperature was 34-42  degrees C. Strain S28bF(T) used
      sulfate and thiosulfate as electron acceptors, but not nitrate. The G+C content
      of the genomic DNA was 56.6 mol%. The fatty acid profile of strain S28bF(T) was
      characterized by the presence of anteiso-C(15 : 0) and C(16 : 0) as the major
      components. Phylogenetic analyses based on genes for 16S rRNA, the alpha subunit
      of dissimilatory sulfite reductase (dsrA) and adenosine-5'-phosphosulfate
      reductase (aprA) revealed that the isolated strain belonged to the class
      Deltaproteobacteria. Its closest relative was Desulfosarcina cetonica DSM 7267(T)
      with a 16S rRNA gene sequence similarity of 93.3 %. Two other strains, S28OL1 and
      S28OL2 were also isolated from the same sediment. These strains were closely
      related to S28bF(T) with 16S rRNA gene sequence similarities of 99 %, and the
      same physiological characteristics were shared with strain S28bF(T). On the basis
      of phylogenetic and phenotypic characterization, a novel species in a new genus,
      Desulfatitalea tepidiphila gen. nov., sp. nov., is proposed to accommodate the
      strains obtained in this study. The type strain is S28bF(T) ( = NBRC 107166(T) =
      DSM 23472(T)).

PMID- 22581902
TI  - Magnetococcus marinus gen. nov., sp. nov., a marine, magnetotactic bacterium that
      represents a novel lineage (Magnetococcaceae fam. nov., Magnetococcales ord.
      nov.) at the base of the Alphaproteobacteria.
AB  - Magnetotactic bacteria are a morphologically, metabolically and phylogenetically
      disparate array of bacteria united by the ability to biomineralize membrane
      encased, single-magnetic-domain mineral crystals (magnetosomes) that cause the
      cell to orientate along the Earth's geomagnetic field. The most commonly observed
      type of magnetotactic bacteria is the ubiquitous magnetotactic cocci, which
      comprise their own phylogenetic group. Strain MC-1(T), a member of this group,
      was isolated from water collected from the oxic-anoxic interface of the
      Pettaquamscutt Estuary in Rhode Island, USA, and cultivated in axenic culture.
      Cells of strain MC-1(T) are roughly spherical, with two sheathed bundles of
      flagella at a single pole (bilophotrichous). Strain MC-1(T) uses polar
      magnetotaxis, and has a single chain of magnetite crystals per cell. Cells grow
      chemolithoautotrophically with thiosulfate or sulfide as the electron donors, and
      chemo-organoheterotrophically on acetate. During autotrophic growth, strain MC
      1(T) relies on the reductive tricarboxylic acid cycle for CO2 fixation. The DNA
      G+C content is 54.2 mol%. The new genus and species Magnetococcus marinus gen.
      nov., sp. nov. are proposed to accommodate strain MC-1(T) ( = ATCC BAA-1437(T)  =
      JCM 17883(T)), which is nominated as the type strain of Magnetococcus marinus. A
      new order (Magnetococcales ord. nov.) and family (Magnetococcaceae fam. nov.) are
      proposed for the reception of Magnetococcus and related magnetotactic cocci,
      which are provisionally included in the Alphaproteobacteria as the most basal
      known lineage of this class.

PMID- 22581903
TI  - Comamonas guangdongensis sp. nov., isolated from subterranean forest sediment,
      and emended description of the genus Comamonas.
AB  - A facultatively anaerobic bacterium, strain CY01(T), isolated from subterranean
      forest sediment collected from Guangdong Province, China, was investigated using
      a polyphasic taxonomic approach. The cells were short rods, Gram-negative, non
      sporulating and motile. Phylogenetic analysis based on 16S rRNA gene sequences
      showed that strain CY01(T) showed highest sequence similarities to Comamonas
      thiooxydans S23(T) (98.0 %), Comamonas testosteroni JCM 5832(T) (97.9 %),
      Comamonas koreensis KCTC 12005(T) (97.7 %) and Comamonas odontotermitis LMG
      23579(T) (97.0 %). The major respiratory quinone was ubiquinone-8. The major
      cellular fatty acids were summed feature 3 (C16 : 1omega6c and/or C16 :
      1omega7c), C16 : 0 and summed feature 8 (C18 : 1omega6c and/or C18 : 1omega7c).
      Based on the phylogenetic analysis, DNA-DNA hybridization, whole-cell fatty acid
      composition as well as biochemical characteristics, strain CY01(T) was clearly
      distinguishable from all recognized species of the genus Comamonas and should be
      classified as a representative of a novel species of the genus, for which the
      name Comamonas guangdongensis sp. nov. is proposed. The type strain is CY01(T) (
      = CCTCC AB 2011133(T) = KACC 16241(T)).

PMID- 22581904
TI  - Paenibacillus vulneris sp. nov., isolated from a necrotic wound.
AB  - A Gram-positive-staining, aerobic, endospore-forming bacterium, isolated from a
      necrotic wound of a 35-year-old man was studied in detail to determine its
      taxonomic position. Based on 16S rRNA gene sequence similarity comparisons,
      strain CCUG 53270(T) was grouped into the genus Paenibacillus, most closely
      related to the type strains of Paenibacillus rigui (97.2 %), Paenibacillus
      xylanisolvens (96.3 %) and Paenibacillus chinjuensis (96.1 %). The 16S rRNA gene
      sequence similarity to strains of other Paenibacillus species was <=96 %.
      Chemotaxonomic characterization supported the allocation of the strain to the
      genus Paenibacillus. The major menaquinones were MK-7 (85 %) and MK-6 (15 %). The
      polar lipid profile contained the major compounds diphosphatidylglycerol,
      phosphatidylmonomethylethanolamine, phosphatidylethanolamine and
      phosphatidylglycerol. The polyamine pattern contained predominantly spermidine.
      The major fatty acids were iso- and anteiso-branched fatty acids. The results of
      physiological and biochemical tests allowed phenotypic differentiation of strain
      CCUG 53270(T) from closely related species. Thus,  strain CCUG 53270(T)
      represents a novel species of the genus Paenibacillus, for which the name
      Paenibacillus vulneris sp. nov. is proposed, with CCUG 53270(T) ( = JCM 18268(T))
      as the type strain.

PMID- 22581905
TI  - Spencermartinsiella ligniputridi sp. nov., a yeast species isolated from rotten
      wood.
AB  - Four strains of a novel heterothallic yeast species were isolated from rotten
      wood samples collected at different locations in Hungary. Analysis of sequences
      of the D1/D2 domain of the large subunit rRNA gene placed the novel species in
      the genus Spencermartinsiella. The novel species can be distinguished from
      Spencermartinsiella europaea, the single species of the genus, and from Candida
      cellulosicola, the only recognized anamorphic species of the Spencermartinsiella
      clade, on the basis of standard phenotypic characteristics. The relatedness among
      the four strains of the novel species and two closely related strains
      representing undescribed yeast species is discussed. The name Spencermartinsiella
      ligniputridi sp. nov. is proposed to accommodate the four novel strains. The type
      and isotype strains of Spencermartinsiella ligniputridi sp. nov. are NCAIM
      Y.01992(T) (=CBS 12585(T)=NRRL Y-48818(T)) and NCAIM Y.01936(I) (=CBS
      12586(I)=NRRL Y-48819(I)), respectively. Two additional strains are NCAIM Y.01991
      and NCAIM Y.01993.

PMID- 22581906
TI  - High prevalence of triazole resistance in Aspergillus fumigatus, especially
      mediated by TR/L98H, in a French cohort of patients with cystic fibrosis.
AB  - OBJECTIVES: Triazole resistance in Aspergillus fumigatus due to a single azole
      resistance mechanism (TR/L98H) is increasingly reported in European countries.
      Data from patients with cystic fibrosis (CF) are limited. Our study aimed to
      investigate the prevalence and molecular mechanisms of azole resistance in A.
      fumigatus in a cohort of patients with CF. METHODS: Eighty-five A. fumigatus
      isolates from 50 CF patients, collected between January 2010 and April 2011, were
      retrospectively analysed for azole resistance using agar plates containing 4 mg/L
      itraconazole. MICs of itraconazole, voriconazole and posaconazole were determined
      according to EUCAST methodology for each isolate able to grow on this medium.
      Species identification was performed by sequencing of the beta-tubulin gene.
      Sequencing analysis of the cyp51A gene and its promoter region was conducted.
      RESULTS: Nine isolates (four patients, 8% prevalence) were able to grow on
      itraconazole-containing agar plates. Itraconazole resistance was confirmed by
      EUCAST methodology (MICs >2 mg/L). All isolates had mutations in the cyp51A gene
      at residues previously involved in azole resistance: L98H (n = 5), M220T (n = 4)
      and G54R (n = 1). One patient had three genetically distinct azole-resistant
      isolates identified during the study. The isolates with L98H that were recovered
      from three patients (6% prevalence) also had the 34 bp tandem repeat in the
      promoter region of cyp51A (TR/L98H) and displayed multiazole resistance.
      CONCLUSIONS: We report an 8% prevalence of itraconazole resistance in CF patients
      in our centre, mostly driven by TR/L98H (6%). Our data confirm that TR/L98H
      occurs in France and can be highly prevalent in CF patients.

PMID- 22581907
TI  - Novel immunomodulatory function of 1,3,4-thiadiazole derivatives with
      leishmanicidal activity.
AB  - OBJECTIVES: Previously, some nitroheteroaryl-1,3,4-thiadiazole derivatives were
      identified to have potent activity against Leishmania sp. The present aim was to
      complete the in vitro analysis, thereby investigating the in vivo efficiency of
      the analogues 15a, 21a and 21b against infected BALB/c mice. METHODS: Following
      parasite inoculation and intraperitoneal drug administration (5 and 20 mg/kg/day)
      for 5 days, the course and size of cutaneous lesions, histopathology of the
      liver, parasite loads in the spleen through limiting dilution assay as well as
      spleen cell activation assays through cytokine secretion profiles were studied in
      BALB/c mice, over a period of 23 and 30 days post-drug injections. RESULTS: The
      analogues significantly decreased lesion size and progression of infection in the
      liver and spleen, and were associated with granuloma formation, which correlates
      with disease regression in the liver of murine hosts. Moreover, the analogues had
      immunomodulatory effects, stimulating interferon-gamma expression and suppressing
      interleukin-10 and interleukin-5 production, favouring type-1 immune responses
      and resolution of the parasitic infection. CONCLUSIONS: Our results highlight
      marked differences between the responses of key anatomical organs to the
      thiadiazole derivatives in comparison with the current antileishmanial drug,
      meglumine antimoniate. The in vivo observations provide further evidence on the
      efficiency of the compounds for Leishmania treatment. The immunomodulatory
      function plays an essential role in enhancing cell-mediated immunity for complete
      clearance of the pathogen.

PMID- 22581908
TI  - Reformulated tenofovir gel for use as a dual compartment microbicide.
AB  - OBJECTIVES: Coital use of 1% tenofovir gel was shown to be modestly effective at
      preventing HIV transmission when applied vaginally in the CAPRISA 004 trial.
      Because the gel is hyperosmolar, which would reduce the integrity of the
      epithelium and induce fluid movement into the lumen, rectal use may not be
      acceptable. This study evaluated the pre-clinical safety and efficacy of a
      reformulated (reduced osmolality) tenofovir gel product. METHODS: Reduced
      glycerine (RG)-tenofovir gel was compared with the original tenofovir gel for
      physiochemical characteristics, product safety and anti-HIV-1 activity. RESULTS:
      The formulations were similar in all characteristics except for osmolality and
      spreadability/firmness. The RG-tenofovir gel had a 73% lower osmolality, a 29.6%
      increase in spreadability and a 27% decrease in firmness as compared with the
      original tenofovir gel. When applied to epithelial cell monolayers, tenofovir gel
      showed a transient reduction in the transepithelial resistance while the RG
      tenofovir gel did not. Both gels retained ectocervical and colorectal explant
      viability. However, tenofovir gel treatment resulted in epithelial stripping that
      was absent after RG-tenofovir gel treatment of the polarized explants. Anti-HIV-1
      activity was confirmed by lack of HIV-1 infection in polarized explants treated
      with either gel as compared with the control explants. CONCLUSIONS: Reducing the
      osmolality of the tenofovir gel resulted in improved epithelial integrity, which
      suggests better safety upon rectal use. The improved gel safety did not
      compromise drug release or anti-HIV-1 activity. These data support the use of
      this gel as a dual compartment microbicide.

PMID- 22581909
TI  - Only surgical resection can identify the second primary lung cancer out of the
      metastasis after gastric cancer surgery.
AB  - OBJECTIVE: Solitary pulmonary lesions (SPLs) in patients with a history of
      malignancy require not only the distinction between benign and malignant, but
      also that between metastatic and primary lesions. We aim to establish the
      clinical strategy for the treatment of a solitary pulmonary lesion that is
      detected during the postoperative surveillance for gastric cancer. METHODS: We
      retrospectively examined the clinical records of the patients who underwent
      curative resection for gastric cancer between January 1999 and December 2009.
      Patients who were diagnosed with solitary pulmonary lesion during the
      postoperative surveillance underwent pulmonary resection, and were reviewed with
      regard to their histological diagnosis and prognosis. RESULTS: Out of a total of
      1017 patients who underwent gastric resections during this period, 13 patients
      with solitary pulmonary lesion underwent pulmonary resection. These tumors were
      shown to be eight primary lung cancers, four metastatic tumors (three from
      gastric cancer) and one benign nodule. Of the eight patients with primary lung
      cancer, seven remained alive after pulmonary resection, including one liver
      metastasis case, and the other died without recurrence. In contrast, the other
      three patients with metastasis from gastric cancer died with distant metastasis,
      despite undergoing curative pulmonary resection. One of these three metastatic
      patients was misdiagnosed as primary lung cancer by transbronchial biopsy before
      surgery. CONCLUSIONS: Solitary pulmonary lesions detected during postoperative
      gastric cancer surveillance should undergo surgical resection to distinguish
      between primary and metastatic disease because of the quite different prognosis
      of these two entities.

PMID- 22581910
TI  - Contactin-1 (CNTN-1) overexpression is correlated with advanced clinical stage
      and lymph node metastasis in oesophageal squamous cell carcinomas.
AB  - OBJECTIVE: Oesophageal squamous cell carcinoma is one of the deadliest
      malignancies worldwide. Contactin-1, a neural adhesion molecule, is implicated in
      tumour invasion and metastasis. The purpose of this study was to investigate the
      expression of CNTN-1 in normal and cancerous oesophageal tissue, and the
      potential relevance to clinicopathological features. METHODS: Thirty normal
      oesophageal tissue samples and 82 primary oesophageal squamous cell carcinoma
      tissue samples were included in this study. The expression levels of CNTN-1, VEGF
      C and HIF-1alpha messenger RNA were determined using reverse transcriptase
      polymerase chain reaction and quantitative real-time polymerase chain reaction.
      The expression of the CNTN-1 protein was measured using immunohistochemistry.
      RESULTS: The expression of CNTN-1 messenger RNA was significantly increased in
      the tumour tissue compared with the normal oesophageal tissue (P=0.001). The
      oesophageal squamous cell carcinoma tissue consistently showed higher CNTN-1
      protein levels. The CNTN-1 expression correlated with the oesophageal squamous
      cell carcinoma stage (P=0.006), lymph node metastasis (P=0.018) and lymphatic
      invasion (P=0.035). The messenger RNA level of CNTN-1 correlated significantly
      with those of VEGF-C and HIF-1alpha. CONCLUSIONS: The expression of CNTN-1 is
      upregulated in the oesophageal squamous cell carcinoma tissue and related to
      stage, lymph node metastasis and lymphatic invasion. Thus, CNTN-1 may be involved
      in the progression and pathogenesis of oesophageal squamous cell carcinoma.

PMID- 22581911
TI  - A case of delayed massive hemothorax caused by the rupture of a pulmonary artery
      pseudoaneurysm after radiofrequency ablation of lung tumors.
AB  - Radiofrequency ablation has been applied as a minimally invasive therapy for the
      local control of lung tumors, including primary and metastatic neoplasms.
      Hemorrhagic complications after radiofrequency ablation can usually be treated
      conservatively, but such complications can be massive and fatal in some cases. In
      this paper, we report the rare case of delayed massive hemothorax caused by the
      rupture of a pulmonary artery pseudoaneurysm after lung radiofrequency ablation
      that was treated using transcatheter coil embolization followed by a left lower
      lobectomy. A 75-year-old woman underwent radiofrequency ablation for the
      treatment of a metastatic lung tumor in the left lower lobe arising from a
      colorectal carcinoma located close to a branch of the pulmonary artery. Thirty
      six hours later, hemothorax and hemorrhagic shock occurred as a result of a
      ruptured pulmonary artery pseudoaneurysm and radiofrequency ablation-induced
      damage to the interlobular pleura. After transcatheter coil embolization of the
      pulmonary artery pseudoaneurysm, she recovered from a state of shock and a left
      lower lobectomy was performed. Histological findings revealed the presence of
      residual tumor cells in the ablated lung tumor. The postoperative course was
      uneventful, and no evidence of recurrence of the primary disease was seen at 1
      year after the surgery. Although hemothorax secondary to the rupture of a
      pulmonary artery pseudoaneurysm after lung radiofrequency ablation is a rare
      complication, it should be recognized as a serious potential complication of lung
      radiofrequency ablation for a tumor located close to the pulmonary artery branch.

PMID- 22581912
TI  - Perceived needs, psychological distress and quality of life of elderly cancer
      patients.
AB  - OBJECTIVE: Very few findings regarding the perceived needs of elderly cancer
      patients have been reported. This study investigated needs and psychological
      distress perceived by and/or quality of life of elderly cancer patients. METHODS:
      Randomly selected ambulatory patients with cancer participated in this study. The
      patients were asked to complete the Short-form Supportive Care Needs Survey
      questionnaire, which covers five domains of need (health system and information,
      psychological, physical, care and support, and sexual); the Hospital Anxiety and
      Depression Scale and the European Organization for Research and Treatment of
      Cancer QLQ-C 30. RESULTS: Complete data were available for 619 cancer patients,
      including 113 subjects who were over 70 years old. The needs and the
      psychological distress perceived by the elderly patients were comparable with
      those perceived by relatively younger patients, although elderly patients
      perceived fewer sexual needs. Regarding the quality of life global health status,
      most symptom-related quality of life parameters were not significantly different
      between the two groups, while significant differences were observed with regard
      to several functional domains, including physical, emotional and social domains
      in addition to financial difficulties. CONCLUSIONS: Only a few differences in the
      needs and the psychological distress perceived by patients existed between the
      elderly and the younger subjects, although some differences in the quality of
      life domains were noted, probably as a result of the influence of aging itself.
      Medical staff should provide elderly cancer patients with good clinical care
      similar to that provided to younger patients while considering the different
      impacts of aging on each quality of life dimension.

PMID- 22581913
TI  - Robotic versus open radical cystectomy: prospective comparison of perioperative
      and pathologic outcomes in Japan.
AB  - OBJECTIVE: In Japan, no study has compared the perioperative outcomes observed
      between robot-assisted radical cystectomy (RARC) and open radical cystectomy
      (ORC). This study aimed at a prospective comparison of the perioperative outcomes
      between RARC and ORC performed by a single surgeon. METHODS: Between 2008 and
      2011, 26 bladder cancer patients underwent radical cystectomy by one surgeon, 11
      robotically and 15 by open procedure. We prospectively collected perioperative
      and pathological data for these 26 patients, and retrospectively compared these
      two different surgical procedures. RESULTS: The RARC cohort had a significant
      decrease in both estimated blood loss (656.9 vs. 1788.7 ml, P=0.0015) and
      allogeneic transfusion requirement (0 vs. 40%, P=0.0237). The total operative
      time was almost the same (P=0.2306) but increased duration of bladder removal and
      lymphadenectomy was observed in the RARC cohort (P=0.0049). Surgery-related
      complication rates within 30 days were not significantly different (P=0.4185).
      Positive surgical margin was observed in three patients in the ORC cohort and in
      one patient in the RARC cohort (P=0.4664). The RARC cohort had a larger number of
      removed lymph nodes than the ORC cohort, and the difference was statistically
      significant (20.7 vs. 13.8, P=0.0421). CONCLUSIONS: We confirmed that RARC is
      safe and yields acceptable outcomes in comparison with ORC for the treatment of
      bladder cancer if it is performed by a surgeon who has experience of over 60
      cases of robot-assisted radical prostatectomy. It is hoped that RARC will gain
      acceptance in Japan as a minimally invasive surgery for muscle-invasive bladder
      cancer.

PMID- 22581914
TI  - Six cases of primary colorectal cancer after living-donor liver transplantation:
      a single-institution experience in Japan.
AB  - OBJECTIVE: Liver-transplant patients have an increased risk of developing primary
      malignancies, possibly due to prolonged immunosuppression. However, no
      information on the incidence and biological characteristics of colorectal cancer
      after living-donor liver transplantation is available. METHODS: The medical
      records of 392 consecutive adult patients who had undergone living-donor liver
      transplantation were retrospectively analyzed. RESULTS: Colorectal cancer
      developed in 6 (1.5%) patients; 3 of 204 (1.5%) presented with hepatic cirrhosis,
      2 of 77 (2.5%) with primary biliary cirrhosis and 1 (2.6%) of 39 with subacute
      fulminant hepatitis, but none of 13 patients with primary sclerosing cholangitis.
      Four patients were successfully treated with curative surgery and one with
      endoscopic resection, while another patient died 3 months after palliative
      surgery because of the progression of peritoneal metastasis. A pathological study
      revealed vessel invasion in all the five cases of surgically removed colorectal
      cancer and nodal metastasis in four (80%) cases. CONCLUSIONS: Colorectal cancer
      develops at a relatively high frequency after living-donor liver transplantation,
      even in non-primary sclerosing cholangitis cases, and might have high malignant
      potential. The screening program for colorectal cancer should be more intensified
      after living-donor liver transplantation compared with that in the general
      population.

PMID- 22581915
TI  - A case of acute adrenal insufficiency unmasked during sunitinib treatment for
      metastatic renal cell carcinoma.
AB  - Sunitinib has recently become a standard treatment for metastatic renal cell
      carcinoma. However, various adverse events have been reported. We present the
      first case of clinically evident adrenal insufficiency during sunitinib therapy.
      A 72-year-old man began sunitinib therapy for bilateral lung and adrenal
      metastases of renal cell carcinoma. His adrenocorticotrophic hormone level was
      93.6 pg/ml (7.2-63.3 pg/ml) before sunitinib treatment, indicating that
      subclinical adrenal insufficiency already existed. Fatigue, which is a frequently
      seen adverse effect of sunitinib treatment, emerged acutely on Day 24 of the
      second cycle. Adrenocorticotrophic hormone and free T4 were high and thyroid
      stimulating hormone was suppressed. Under the clinical diagnosis of acute adrenal
      insufficiency with thyrotoxicosis, a low dose of steroid was administered.
      Fatigue was completely ameliorated by the following morning, although free T4 was
      still high and thyroid-stimulating hormone was still low. Therefore,
      hypermetabolism due to thyrotoxicosis unmasked adrenal insufficiency in our case.
      Physicians should be aware of this rare but potentially fatal complication when
      severe acute fatigue develops in patients with subclinical adrenal insufficiency.

PMID- 22581916
TI  - Protective role for myeloid specific KLF2 in atherosclerosis.

PMID- 22581917
TI  - Myocardial Isl(+)land: a place with lots of rhythm, but no beat.

PMID- 22581918
TI  - An ACE up your sleeve: 2 is better than 1.

PMID- 22581919
TI  - Why don't macrophages leave atherosclerotic lesions?

PMID- 22581920
TI  - Autophagy mediates the metabolic benefits of endurance training.

PMID- 22581921
TI  - Cardiac side population cells: moving toward the center stage in cardiac
      regeneration.
AB  - Over the past decade, extensive work in animal models and humans has identified
      the presence of adult cardiac progenitor cells, capable of cardiomyogenic
      differentiation and likely contributors to cardiomyocyte turnover during normal
      development and disease. Among cardiac progenitor cells, there is a distinct
      subpopulation, termed "side population" (SP) progenitor cells, identified by
      their unique ability to efflux DNA binding dyes through an ATP-binding cassette
      transporter. This review highlights the literature on the isolation,
      characterization, and functional relevance of cardiac SP cells. We review the
      initial discovery of cardiac SP cells in adult myocardium as well as their
      capacity for functional cardiomyogenic differentiation and role in cardiac
      regeneration after myocardial injury. Finally, we discuss recent advances in
      understanding the molecular regulators of cardiac SP cell proliferation and
      differentiation, as well as likely future areas of investigation required to
      realize the goal of effective cardiac regeneration.

PMID- 22581923
TI  - The future of optical mapping is bright: RE: review on: "Optical Imaging of
      Voltage and Calcium in Cardiac Cells and Tissues" by Herron, Lee, and Jalife.

PMID- 22581924
TI  - Extragonadal seminoma presenting as a large mass in the pelvic cavity without c
      kit-activating mutations.
AB  - Extragonadal germ cell tumors are relatively rare tumors, which usually occur in
      the mediastinum or retroperitoneum. In this report, we present a case of primary
      seminoma arising in the pelvic cavity. A 58-year-old man with urinary retention
      and abdominal distension was admitted to our hospital. Computed tomography and
      magnetic resonance imaging demonstrated a large mass in the pelvic cavity.
      Histological examination of the specimens obtained by open biopsy revealed
      seminomatous malignant cells. Immunohistochemical studies detected vimentin,
      placental alkaline phosphatase and c-kit. Taking these results together with the
      patient's other clinical manifestations, this case was diagnosed as extragonadal
      seminoma without c-kit-activating mutations, and chemotherapy followed by
      radiation therapy was successful. Primary seminoma in the pelvic cavity is
      extremely rare, but should be considered a cause of pelvic mass formation.

PMID- 22581925
TI  - Higher volume endovascular stroke centers have faster times to treatment, higher
      reperfusion rates and higher rates of good clinical outcomes.
AB  - BACKGROUND AND PURPOSE: Technological advances have helped to improve the
      efficiency of treating patients with large vessel occlusion in acute ischemic
      stroke. Unfortunately, the sequence of events prior to reperfusion may lead to
      significant treatment delays. This study sought to determine if high-volume (HV)
      centers were efficient at delivery of endovascular treatment approaches. METHODS:
      A retrospective review was performed of nine centers to assess a series of time
      points from obtaining a CT scan to the end of the endovascular procedure.
      Demographic, radiographic and angiographic variables were assessed by
      multivariate analysis to determine if HV centers were more efficient at delivery
      of care. RESULTS: A total of 442 consecutive patients of mean age 66 +/- 14 years
      and median NIH Stroke Scale score of 18 were studied. HV centers were more likely
      to treat patients after intravenous administration of tissue plasminogen
      activator and those transferred from outside hospitals. After adjusting for
      appropriate variables, HV centers had significantly lower times from CT
      acquisition to groin puncture (OR 0.991, 95% CI 0.989 to 0.997, p=0.001) and
      total procedure times (OR 0.991, 95% CI 0.986 to 0.996, p=0.001). Additionally,
      patients treated at HV centers were more likely to have a good clinical outcome
      (OR 1.86, 95% CI 1.11 to 3.10, p<0.018) and successful reperfusion (OR 1.82, 95%
      CI 1.16 to 2.86, p<0.008). CONCLUSIONS: Significant delays occur in treating
      patients with endovascular therapy in acute ischemic stroke, offering
      opportunities for improvements in systems of care. Ongoing prospective clinical
      trials can help to assess if HV centers are achieving better clinical outcomes
      and higher reperfusion rates.

PMID- 22581926
TI  - Sonic hedgehog-modified human CD34+ cells preserve cardiac function after acute
      myocardial infarction.
AB  - RATIONALE: Ischemic cardiovascular disease represents one of the largest
      epidemics currently facing the aging population. Current literature has
      illustrated the efficacy of autologous, stem cell therapies as novel strategies
      for treating these disorders. The CD34+ hematopoetic stem cell has shown
      significant promise in addressing myocardial ischemia by promoting angiogenesis
      that helps preserve the functionality of ischemic myocardium. Unfortunately, both
      viability and angiogenic quality of autologous CD34+ cells decline with advanced
      age and diminished cardiovascular health. OBJECTIVE: To offset age- and health
      related angiogenic declines in CD34+ cells, we explored whether the therapeutic
      efficacy of human CD34+ cells could be enhanced by augmenting their secretion of
      the known angiogenic factor, sonic hedgehog (Shh). METHODS AND RESULTS: When
      injected into the border zone of mice after acute myocardial infarction, Shh
      modified CD34+ cells (CD34(Shh)) protected against ventricular dilation and
      cardiac functional declines associated with acute myocardial infarction.
      Treatment with CD34(Shh) also reduced infarct size and increased border zone
      capillary density compared with unmodified CD34 cells or cells transfected with
      the empty vector. CD34(Shh) primarily store and secrete Shh protein in exosomes
      and this storage process appears to be cell-type specific. In vitro analysis of
      exosomes derived from CD34(Shh) revealed that (1) exosomes transfer Shh protein
      to other cell types, and (2) exosomal transfer of functional Shh elicits
      induction of the canonical Shh signaling pathway in recipient cells. CONCLUSIONS:
      Exosome-mediated delivery of Shh to ischemic myocardium represents a major
      mechanism explaining the observed preservation of cardiac function in mice
      treated with CD34(Shh) cells.

PMID- 22581927
TI  - Neurohormonal regulation of cardiac histone deacetylase 5 nuclear localization by
      phosphorylation-dependent and phosphorylation-independent mechanisms.
AB  - RATIONALE: Myocyte enhancer factor 2 (MEF2) transcription factors drive the
      genetic reprogramming that precipitates pathological cardiac hypertrophy and
      remodeling. Class II histone deacetylase (HDAC) isoforms, such as HDAC5, act as
      signal-responsive repressors of MEF2 activity in cardiac myocytes and their
      nuclear export provides a key mechanism for the neurohormonal induction of such
      activity. OBJECTIVE: To delineate the mechanism(s) through which 2 clinically
      relevant neurohormonal stimuli, endothelin-1 (ET1) and the beta-adrenergic
      receptor (beta-AR) agonist isoproterenol (ISO), may regulate HDAC5 nuclear
      localization in adult cardiac myocytes. METHODS AND RESULTS: ET1 induced HDAC5
      phosphorylation and nuclear export in ventricular myocytes from the adult rat
      heart. Use of a novel, highly selective protein kinase D (PKD) inhibitor and a
      nonphosphorylatable HDAC5 mutant revealed that PKD-mediated phosphorylation was
      necessary for ET1-induced HDAC5 nuclear export. In contrast, ISO reduced HDAC5
      phosphorylation in the presence or absence of ET1 but still induced HDAC5 nuclear
      export. ISO-induced HDAC5 nuclear export occurred through a beta(1)-AR-mediated
      oxidative process that was independent of PKD, protein kinase A, and
      Ca(2+)/calmodulin-dependent kinase II activities. Although ET1 and ISO shared a
      similar ability to induce HDAC5 nuclear export, albeit through distinct
      phosphorylation-dependent versus phosphorylation-independent mechanisms, ISO
      induced a significantly greater increase in MEF2 activity. CONCLUSIONS: PKD
      mediated HDAC5 phosphorylation and nuclear export are unlikely to be of major
      importance in regulating MEF2-driven cardiac remodeling in the presence of
      sympathetic activity with intact beta(1)-AR signaling, which would not only
      counteract HDAC5 phosphorylation but also induce HDAC5 nuclear export through a
      novel phosphorylation-independent, oxidation-mediated mechanism. Inhibition of
      this mechanism may contribute to the therapeutic efficacy of beta(1)-AR
      antagonists in heart failure.

PMID- 22581928
TI  - Inefficient reprogramming of fibroblasts into cardiomyocytes using Gata4, Mef2c,
      and Tbx5.
AB  - RATIONALE: Direct reprogramming of fibroblasts into cardiomyocytes is a novel
      strategy for cardiac regeneration. However, the key determinants involved in this
      process are unknown. OBJECTIVE: To assess the efficiency of direct fibroblast
      reprogramming via viral overexpression of GATA4, Mef2c, and Tbx5 (GMT). METHODS
      AND RESULTS: We induced GMT overexpression in murine tail tip fibroblasts (TTFs)
      and cardiac fibroblasts (CFs) from multiple lines of transgenic mice carrying
      different cardiomyocyte lineage reporters. We found that the induction of GMT
      overexpression in TTFs and CFs is inefficient at inducing molecular and
      electrophysiological phenotypes of mature cardiomyocytes. In addition,
      transplantation of GMT infected CFs into injured mouse hearts resulted in
      decreased cell survival with minimal induction of cardiomyocyte genes.
      CONCLUSIONS: Significant challenges remain in our ability to convert fibroblasts
      into cardiomyocyte-like cells and a greater understanding of cardiovascular
      epigenetics is needed to increase the translational potential of this strategy.

PMID- 22581929
TI  - A touch of MS: therapeutic mislabeling.
AB  - When psychogenic symptomatology is at play, a spectrum of ethical problems and
      considerations arise when patients want, and at times, insist on being given an
      inaccurate neurologic diagnosis. We use the example of multiple sclerosis (MS) to
      highlight the value considerations for clinicians when they face these types of
      cases. Given the ambiguities involved in its diagnosis and the significant risks
      of its treatment, MS represents a rich case study. This discussion highlights the
      potential harms of mislabeling such patients with MS when the neurologist is
      confident they do not have MS and offers suggestions about how to approach and
      manage these patients. Despite being expedient and well-intentioned, labeling
      psychogenic symptoms with a medically inaccurate diagnosis, such as a "touch of
      MS," constitutes a "therapeutic mislabeling" and sacrifices ethically important
      values incommensurate with the benefits gained.

PMID- 22581930
TI  - "Undiagnosing" multiple sclerosis: the challenge of misdiagnosis in MS.
AB  - OBJECTIVE: To describe the clinical characteristics of encounters with patients
      misdiagnosed with multiple sclerosis (MS). METHODS: A cross-sectional Internet
      based physician survey of MS specialists was performed. RESULTS: The response
      rate for the survey was 50.4%. Of those who responded, the majority (95%)
      reported having evaluated 1 or more patients who had been diagnosed with MS, but
      who they strongly felt did not have MS, within the last year. The majority of
      respondents (>90%) also reported the use of disease-modifying therapy in a
      proportion of these patients. Most respondents (94%) found clinical encounters
      with these patients equally or more challenging than giving a new diagnosis of
      MS. Fourteen percent of respondents reported that they did not always inform such
      patients of their opinion that they did not have MS. CONCLUSIONS: The
      misdiagnosis of MS is common and has significant consequences for patient care
      and health care system costs. Caring for a patient with a misdiagnosis of MS is
      challenging, and at times honest disclosure of a misdiagnosis represents an
      important ethical concern for neurologists. More data are needed on this patient
      population to improve diagnostic acumen and the care of these patients.

PMID- 22581922
TI  - Biochemistry, physiology, and pathophysiology of NADPH oxidases in the
      cardiovascular system.
AB  - The NADPH oxidase (Nox) enzymes are critical mediators of cardiovascular
      physiology and pathophysiology. These proteins are expressed in virtually all
      cardiovascular cells, and regulate such diverse functions as differentiation,
      proliferation, apoptosis, senescence, inflammatory responses and oxygen sensing.
      They target a number of important signaling molecules, including kinases,
      phosphatases, transcription factors, ion channels, and proteins that regulate the
      cytoskeleton. Nox enzymes have been implicated in many different cardiovascular
      pathologies: atherosclerosis, hypertension, cardiac hypertrophy and remodeling,
      angiogenesis and collateral formation, stroke, and heart failure. In this review,
      we discuss in detail the biochemistry of Nox enzymes expressed in the
      cardiovascular system (Nox1, 2, 4, and 5), their roles in cardiovascular cell
      biology, and their contributions to disease development.

PMID- 22581931
TI  - Multiple sclerosis or multiple possibilities: the continuing problem of
      misdiagnosis.

PMID- 22581932
TI  - Sublytic concentrations of Staphylococcus aureus Panton-Valentine leukocidin
      alter human PMN gene expression and enhance bactericidal capacity.
AB  - CA-MRSA infections are often caused by strains encoding PVL, which can cause
      lysis of PMNs and other myeloid cells in vitro, a function considered widely as
      the primary means by which PVL might contribute to disease. However, at sublytic
      concentrations, PVL can function as a PMN agonist. To better understand this
      phenomenon, we investigated the ability of PVL to alter human PMN function. PMNs
      exposed to PVL had enhanced capacity to produce O(2)(-) in response to fMLF, but
      unlike priming by LPS, this response did not require TLR signal transduction. On
      the other hand, there was subcellular redistribution of NADPH oxidase components
      in PMNs following exposure of these cells to PVL--a finding consistent with
      priming. Importantly, PMNs primed with PVL had an enhanced ability to bind/ingest
      and kill Staphylococcus aureus. Priming of PMNs with other agonists, such as IL-8
      or GM-CSF, altered the ability of PVL to cause formation of pores in the plasma
      membranes of these cells. Microarray analysis revealed significant changes in the
      human PMN transcriptome following exposure to PVL, including up-regulation of
      molecules that regulate the inflammatory response. Consistent with the microarray
      data, mediators of the inflammatory response were released from PMNs after
      stimulation with PVL. We conclude that exposure of human PMNs to sublytic
      concentrations of PVL elicits a proinflammatory response that is regulated in
      part at the level of gene expression. We propose that PVL-mediated priming of
      PMNs enhances the host innate immune response.

PMID- 22581933
TI  - miRNA-125b regulates TNF-alpha production in CD14+ neonatal monocytes via post
      transcriptional regulation.
AB  - Neonates, although deficient in cell immunity, frequently reveal sepsis with
      augmented proinflammatory reactions. Here, we found that neonatal monocytes
      produced significantly higher TNF-alpha mRNA and protein than adult monocytes.
      Assessment of the transcriptional factor found no significant difference of NF
      kappaB p65 level between neonatal and adult monocytes. Addition of Act D to
      access the half-life of TNF-alpha mRNA revealed no significant difference of the
      LPS-induced TNF-alpha mRNA half-life between them, whereas CHX increased neonatal
      TNF-alpha mRNA significantly. This suggests that a post-transcriptional mechanism
      involves the augmentation of TNF-alpha production by neonatal monocytes. To
      examine whether miRNA was involved in the post-transcriptional regulation,
      differential displays of miRNA array between neonatal and adult MNCs were
      performed, along with the discovery of hsa-miR-103, hsa-miR-125b, hsa-miR-130a,
      hsa-miR-454-3p, and hsa-miR-542-3p, which were greater than a twofold decrease or
      increase after LPS treatment for 4 h. The functional validation identified that
      miR-125b decreased significantly in association with higher TNF-alpha expression
      by neonatal monocytes after LPS stimulation. Transfection of the miR-125b
      precursor into neonatal monocytes significantly repressed the TNF-alpha mRNA and
      protein expression, suggesting that miR-125b negatively regulates TNF-alpha
      expression in neonatal monocytes. Modulation of miRNA expression may be used to
      regulate TNF-alpha production in newborns with altered proinflammatory reactions.

PMID- 22581935
TI  - Targeted metabolomics for discrimination of systemic inflammatory disorders in
      critically ill patients.
AB  - The occurrence of systemic inflammatory response syndrome (SIRS) remains a major
      problem in intensive care units with high morbidity and mortality. The
      differentiation between noninfectious and infectious etiologies of this disorder
      is challenging in routine clinical practice. Many biomarkers have been suggested
      for this purpose; however, sensitivity and specificity even of high-ranking
      biomarkers remain insufficient. Recently, metabolic profiling has attracted
      interest for biomarker discovery. The objective of this study was to identify
      metabolic biomarkers for differentiation of SIRS/sepsis. A total of 186 meta
      bolites comprising six analyte classes were determined in 143 patients (74 SIRS,
      69 sepsis) by LC-MS/MS. Two markers (C10:1 and PCaaC32:0) revealed significantly
      higher concentrations in sepsis. A classification model comprising these markers
      resulted in 80% and 70% correct classifications in a training set and a test set,
      respectively.This study demonstrates that acylcarnitines and
      glycerophosphatidylcholines may be helpful for differentiation of infectious from
      noninfectious systemic inflammation due to their significantly higher
      concentration in sepsis patients. Considering the well known pathophysiological
      relevance of lipid induction by bacterial components, metabolites as identified
      in this study are promising biomarker candidates in the differential diagnosis of
      SIRS and sepsis.

PMID- 22581934
TI  - NLRs, inflammasomes, and viral infection.
AB  - NLR proteins are innate immune sensors that respond to microbial infection. Upon
      pathogen infection, some NLR proteins form large complexes, called inflammasomes,
      which activate caspase-1 and induce the production of active IL-1beta and IL-18.
      Activation of inflammasomes can also lead to an inflammatory cell death program,
      named pyroptosis. In this review, we will discuss the role of various NLR
      proteins in sensing different viral infections, as well as the strategies used by
      several RNA and DNA viruses to counteract the antiviral effects of NLR-dependent
      inflammasomes.

PMID- 22581937
TI  - Continuation of high-dose vancomycin despite nephrotoxicity.

PMID- 22581936
TI  - Clinical application of exome sequencing in undiagnosed genetic conditions.
AB  - BACKGROUND: There is considerable interest in the use of next-generation
      sequencing to help diagnose unidentified genetic conditions, but it is difficult
      to predict the success rate in a clinical setting that includes patients with a
      broad range of phenotypic presentations. METHODS: The authors present a pilot
      programme of whole-exome sequencing on 12 patients with unexplained and apparent
      genetic conditions, along with their unaffected parents. Unlike many previous
      studies, the authors did not seek patients with similar phenotypes, but rather
      enrolled any undiagnosed proband with an apparent genetic condition when
      predetermined criteria were met. RESULTS: This undertaking resulted in a likely
      genetic diagnosis in 6 of the 12 probands, including the identification of
      apparently causal mutations in four genes known to cause Mendelian disease (TCF4,
      EFTUD2, SCN2A and SMAD4) and one gene related to known Mendelian disease genes
      (NGLY1). Of particular interest is that at the time of this study, EFTUD2 was not
      yet known as a Mendelian disease gene but was nominated as a likely cause based
      on the observation of de novo mutations in two unrelated probands. In a seventh
      case with multiple disparate clinical features, the authors were able to identify
      homozygous mutations in EFEMP1 as a likely cause for macular degeneration (though
      likely not for other features). CONCLUSIONS: This study provides evidence that
      next-generation sequencing can have high success rates in a clinical setting, but
      also highlights key challenges. It further suggests that the presentation of
      known Mendelian conditions may be considerably broader than currently recognised.

PMID- 22581939
TI  - Tobacco smoking, quitting, and relapsing among adult males in Mainland China: the
      China Seven Cities Study.
AB  - INTRODUCTION: Despite an estimated 1 million tobacco-related deaths annually in
      China, public health officials face overwhelming barriers to implementing
      effective tobacco control policies and programs. Models of effective tobacco
      control can be adapted for Chinese tobacco use and culture based on reliable and
      valid data regarding predictors of smoking and abstaining. METHODS: As part of
      the China Seven Cities Study to assess the role of rapid social, economic, and
      cultural change on tobacco use and related health practices and outcomes, 4,072
      adult male smokers provided data in 3 annual waves. Measures included current
      smoking, nicotine dependence, readiness for quitting, perceived stress,
      hostility, depressive symptoms, as well as covariates (e.g., age, marital status,
      educational attainment, and family income). RESULTS: Odds of being abstinent at
      Wave 3 were increased by: lower nicotine dependence at Wave 1 and becoming less
      dependent between Waves 1 and 3; progressing beyond the contemplation stage
      between Waves 1 and 3; perceiving less stress, whether initially at Wave 1 or
      over time from Wave 1 to Wave 3; and lower hostility scores at Wave 1 and
      decreased hostility from Wave 1 to Wave 3. Among those who quit, odds of
      remaining abstinent rather than relapsing by Wave 3 were higher among those who
      were less dependent at Wave 1 and who became less dependent from Wave 1 to Wave
      3; and those who showed decreases in hostility from Wave 1 to Wave 3.
      CONCLUSIONS: The public health challenge posed by very high prevalence of male
      smoking in China can be met by policies and programs that lead to successful long
      term cessation. This can only be done successfully by designing interventions
      based on knowledge of the country's smokers and the current study suggests
      several elements.

PMID- 22581940
TI  - Sexual-orientation disparities in cigarette smoking in a longitudinal cohort
      study of adolescents.
AB  - INTRODUCTION: Youths with a minority sexual orientation (i.e., gay, lesbian,
      bisexual, and mostly heterosexual) are at high risk for cigarette smoking. We
      examined sexual-orientation disparities in smoking during adolescence and
      emerging adulthood and investigated the role of age at first smoking in
      contributing to smoking disparities. METHODS: We used data from the Growing Up
      Today Study, a large longitudinal cohort of adolescents followed from ages 12 to
      24 years (N = 13,913). Self-administered questionnaires filled out annually or
      biennially assessed age at first smoking, current smoking, frequency of smoking,
      number of cigarettes smoked daily, and nicotine dependence. Proportional hazards
      survival analysis and repeated measures regression estimated sexual-orientation
      differences in smoking. RESULTS: Compared with completely heterosexuals,
      lesbian/gay, bisexual, and mostly heterosexual youths smoked their first
      cigarette at younger ages, were more likely to be current smokers, and had higher
      frequency of smoking. Among past-year smokers, sexual-minority females smoked
      more cigarettes daily and scored higher on nicotine dependence than completely
      heterosexual females. In some instances, gender and age modified relationships
      between sexual orientation and smoking, with relative risk accentuated in female
      sexual minorities and in sexual minorities during younger ages. Younger age of
      smoking onset contributed to elevated smoking in mostly heterosexuals and
      bisexuals, and to a lesser extent in lesbians, but not in gay males. CONCLUSIONS:
      Sexual-orientation minorities are at greater risk for smoking during adolescence
      and emerging adulthood than heterosexuals. Disparities are larger in females and
      evident in early adolescence. Prevention and cessation efforts should target this
      population, preferably beginning in early adolescence.

PMID- 22581941
TI  - The association between implicit and explicit attitudes toward smoking and
      support for tobacco control measures.
AB  - INTRODUCTION: This study examined the association between implicit and explicit
      attitudes toward smoking and support for tobacco control policies. METHODS:
      Participants were from an ongoing longitudinal study of the natural history of
      smoking who also completed a web-based assessment of implicit attitudes toward
      smoking (N = 1,337). Multiple regression was used to test the association between
      covariates (sex, age, educational attainment, parent status, and smoking status),
      implicit attitude toward smoking, and explicit attitude toward smoking and
      support for tobacco control policies. The moderating effect of the covariates on
      the relation between attitudes and support for policies was also tested. RESULTS:
      Females, those with higher educational attainment, parents, and nonsmokers
      expressed more support for tobacco control policy measures. For nonsmokers, only
      explicit attitude was significantly associated with support for policies. For
      smokers, both explicit and implicit attitudes were significantly associated with
      support. The effect of explicit attitude was stronger for those with lower
      educational attainment. CONCLUSIONS: Both explicit and implicit smoking attitudes
      are important for building support for tobacco control policies, particularly
      among smokers. More research is needed on how to influence explicit and implicit
      attitudes to inform policy advocacy campaigns.

PMID- 22581942
TI  - Attitudes of business people to proposed smokefree shopping streets.
AB  - OBJECTIVE: To investigate the attitudes of business people toward a possible
      smokefree policy along a route of major shopping streets, the "Golden Mile" (GM)
      in central Wellington, New Zealand. METHODS: Businesses on the GM (n = 303) were
      visited in June-July 2011. Either the owner or manager from each business was
      surveyed. RESULTS: A response rate of 65.6% (n = 198) was achieved, with 13.3%
      declining to participate, and further contact not being productive for 21.2%.
      Support for making the GM smokefree was 43.4% (95% CI = 36.7%-50.4%), with the
      remainder opposed. There was significantly higher support among business people
      who were nonsmokers versus smokers (relative risk = 2.95; 95% CI = 1.48-5.89).
      Overall, 83.3% (95% CI = 77.0%-88.0%) of respondents stated that a smokefree GM
      would have either a positive or negligible impact on their business (nonconcern),
      compared with a negative impact (at 16.7%). Nonconcern about the business impact
      of a smokefree GM was significantly greater for nonfood businesses (89.9%) versus
      food businesses (64.0%; p < .001), after adjusting for respondent age, smoking
      status, and gender in logistic regression models. CONCLUSIONS: The modest support
      for introducing a smokefree streets policy by GM business people may reflect the
      negligible promotion of the idea in this setting. Nevertheless, the likely
      business impact of a smokefree streets policy was not a concern for the large
      majority of these business people, so this may not be a significant barrier to
      policy development. This type of study can contribute to the process for
      developing smokefree streets and other outdoor areas, by gauging sector support.

PMID- 22581943
TI  - Tobacco consumption in Mozambique: use of distinct types of tobacco across urban
      and rural settings.
AB  - INTRODUCTION: Monitoring tobacco consumption patterns is essential to define and
      evaluate strategies to control the tobacco epidemic. We aimed to quantify the use
      of smoked (manufactured/hand-rolled cigarettes) and smokeless (snuff/chew)
      tobacco, according to sociodemographic characteristics, in adult Mozambicans.
      METHODS: A national representative sample (n = 3,323) of subjects aged 25-64
      years was evaluated in 2005 following the World Health Organization Stepwise
      Approach to Chronic Disease Risk Factor Surveillance (STEPS), which included the
      assessment of tobacco consumption with the quantification of each type of tobacco
      used daily. We computed prevalences, and age- and education-adjusted prevalence
      ratios (PRs), with 95% CIs. RESULTS: Daily smoking was reported by 9.1% (95% CI =
      5.0-13.1) of women (manufactured, 3.4%; hand-rolled, 5.6%) and 33.6% (95% CI =
      29.3-38.0) of men (manufactured, 18.7%; hand-rolled, 14.8%). Daily manufactured
      cigarette smoking was significantly more frequent in men (urban: PR = 14.62, 95%
      CI = 7.59-28.55; rural: PR = 4.32, 95% CI = 2.42-7.71). Daily hand-rolled
      cigarette smoking was three- to fourfold more frequent among men and nearly 80%
      less frequent in urban areas, regardless of sex. The prevalence of daily
      smokeless tobacco use was 7.4% (95% CI = 4.6-10.2) in women (chew, 6.4%; snuff,
      1.0%) and 3.4% (95% CI = 1.7-5.2) in men (chew, 1.6%; snuff, 1.8%). Daily
      smokeless tobacco consumption was significantly less frequent in urban areas only
      among men (PR = 0.05, 95% CI = 0.01-0.33). CONCLUSIONS: Despite the relatively
      low levels of manufactured cigarette smoking, traditional forms of tobacco
      consumption are frequent, especially among women and in rural settings, showing
      the need for control measures to target specifically different patterns of
      consumption.

PMID- 22581944
TI  - Condom use among female sex workers and their non-commercial partners: effects of
      a sexual risk intervention in two Mexican cities.
AB  - The purpose of this study was to examine whether a brief behavioural intervention
      promoting condom use among female sex workers (FSWs) and their clients had the
      added benefit of increasing condom use among FSWs and their steady, non
      commercial partners (e.g. husbands, boyfriends). Participants were 362 FSWs, aged
      >=18 years, living in Tijuana or Ciudad Juarez, Mexico, who received a
      behavioural intervention to promote condom use with clients. Repeated-measures
      negative binomial regression was used to assess FSWs' condom use with steady
      partners versus clients across time. Results showed that FSWs engaged in
      unprotected sex with steady partners more than with their clients, and that the
      intervention changed FSWs' condom use with clients but not their steady partners.
      HIV-prevention interventions for FSWs should promote consistent condom use across
      partner type. Targeting couples rather than individuals may also be necessary.

PMID- 22581945
TI  - Use of conjoint analysis to assess HIV vaccine acceptability: feasibility of an
      innovation in the assessment of consumer health-care preferences.
AB  - Engaging consumers in prospectively shaping strategies for dissemination of
      health-care innovations may help to ensure acceptability. We examined the
      feasibility of using conjoint analysis to assess future HIV vaccine acceptability
      among three diverse communities: a multiethnic sample in Los Angeles, CA, USA (n
      = 143); a Thai resident sample in Los Angeles (three groups; n = 27) and an
      Aboriginal peoples sample in Toronto (n = 13). Efficacy had the greatest impact
      on acceptability for all three groups, followed by cross-clade protection, side
      effects and duration of protection in the Los Angeles sample; side-effects and
      duration of protection in the Thai-Los Angeles sample; and number of doses and
      duration of protection in the Aboriginal peoples-Toronto sample. Conjoint
      analysis provided insights into universal and population-specific preferences
      among diverse end users of future HIV vaccines, with implications for evidence
      informed targeting of dissemination efforts to optimize vaccine uptake.

PMID- 22581947
TI  - A systematic review and meta-analysis of the prevalence of chlamydia, gonorrhoea
      and syphilis in incarcerated persons.
AB  - Communicable diseases are common in people who are incarcerated. We aimed to
      define the prevalence of chlamydia, gonorrhoea and syphilis in people who are
      incarcerated and to identify subgroups with the highest risk of infection. We
      searched for prevalence studies of chlamydia, gonorrhoea or syphilis in
      incarcerated populations. Pooled estimates were generated, and meta-regression
      was conducted. Random effects models yielded pooled prevalence estimates of 5.75%
      (95% confidence interval [CI] 5.01, 6.48) and 12.31% (95% CI 10.61, 14.01) for
      chlamydia in men and women, 1.4% (95% CI 1.09, 1.70) and 5.73% (4.76, 6.69) for
      gonorrhoea in men and women, and 2.45% (95% CI 2.08, 2.82) and 6.10% (95% CI
      4.75, 7.46) for syphilis in men and women, respectively. Each infection was
      associated with female gender in meta-regression models. Chlamydia, gonorrhoea
      and syphilis are highly prevalent in these populations. Primary and secondary
      prevention efforts could improve individual and population health.

PMID- 22581946
TI  - Human papillomavirus prevalence, cervical abnormalities and risk factors among
      female sex workers in Lima, Peru.
AB  - Female sex workers (FSWs) are at high risk of human papillomavirus (HPV)
      infection. Questionnaires were administered to 200 FSWs aged 18-26 years in Lima,
      Peru, to gather risk behaviours, and cervical swab samples were collected for Pap
      smears and HPV DNA testing as part of a longitudinal study. Participants reported
      a median of 120 clients in the past month, and 99.2% reported using condoms with
      clients. The prevalence of any HPV in cervical samples was 66.8%; 34 (17.1%)
      participants had prevalent HPV 16 or 18, and 92 (46.2%) had one or more oncogenic
      types. Fifteen women had abnormal Pap smears, 13 of which were HPV DNA positive.
      Fewer years since first sex was associated with oncogenic HPV prevalence in a
      model adjusted for previous sexually transmitted infection (STI) status and
      condom use with partners (prevalence ratio = 0.77, 95% confidence interval [CI] =
      0.60-0.97). Our data confirm the high rates of HPV transmission among FSWs in
      Peru, highlighting the need for early and effective strategies to prevent
      cervical cancer.

PMID- 22581948
TI  - Pruritus in HIV-infected patients in the era of combination antiretroviral
      therapy: a study of its prevalence and causes.
AB  - Pruritus is a common symptom in HIV-infected patients. However, there is a lack
      of studies examining this symptom. We investigated the prevalence of pruritus and
      its causes in this population by offering the possibility of participating in a
      skin health programme to all HIV-infected patients who attended our service in
      Alicante, Spain. Those who accepted (n = 303) underwent an interview and a
      detailed physical examination by specialists from the Dermatology Department.
      Between May 2003 and October 2003, 94 patients (31%) reported pruritus: xerosis,
      seborrhoeic eczema and interdigital tinea pedis were the most frequent
      dermatological entities responsible for this symptom. Patients with pruritus had
      higher viral loads (P = 0.006). We conclude that pruritus is still a frequent
      symptom in HIV-infected patients. To the best of our knowledge this is the first
      prevalence study of pruritus in an HIV population in the combination
      antiretroviral therapy (cART) era.

PMID- 22581949
TI  - Adeno-associated virus may play a protective role against human papillomavirus
      induced cervical lesions independent of HIV serostatus.
AB  - This study investigated the prevalence of adeno-associated virus (AAV) and human
      papillomavirus (HPV) DNA in cervical samples of HIV-seropositive and 
      seronegative women attending a clinic in south-eastern Brazil. Both viruses were
      investigated by polymerase chain reaction (PCR) and cytological exams were
      performed. AAV was typed by PCR and restriction fragment length polymorphism
      analysis. AAV prevalence was 19.7% (56/284), with 18.7% (21/112) and 20.3%
      (35/172) in HIV-positive and -negative women, respectively. AAV type 2 was the
      single virus type detected. AAV was detected with higher frequency in HPV
      infected women (P < 0.05) as was HPV in HIV-positive women (P < 0.05). The AAV
      HPV co-infected women showed a lower rate of atypical squamous cells of
      undetermined significance or cervical intraepithelial neoplasia development
      compared with those infected only with HPV. The prevalence of AAV2 confirms this
      type as the most common in human samples. This is the first report examining AAV
      in cervical samples of HIV-infected women and indicates that HIV infection does
      not appear to influence AAV prevalence or AAV-HPV co-infection.

PMID- 22581950
TI  - The relationship between HIV testing and CD4 counts at HIV diagnosis among newly
      diagnosed HIV-1 patients in Japan.
AB  - The aim of this study was to investigate the factors relating to CD4 level at HIV
      diagnosis and HIV testing behaviour. Participants were newly diagnosed patients
      (n = 654) in Japan from 2000 to 2005. Around 75% of participants were diagnosed
      at hospital and clinics. Mean CD4 counts at diagnosis through voluntary HIV
      testing, screening tests and testing due to concomitant sexually transmitted
      infection (STI) were 368, 336 and 316 cells/MUL, respectively. In contrast, the
      mean CD4 count where testing was due to the presence of HIV-related clinical
      symptoms was 151 cells/MUL (P < 0.0001). Compared with those diagnosed at their
      first HIV test, those who had undertaken multiple HIV tests prior to diagnosis
      showed CD4 counts that increased significantly (P < 0.0001) in relation to the
      number of tests undertaken: CD4 count at first test was 232 cells/MUL, second
      test 346 cells/MUL and third or additional tests 439 cells/MUL. According to our
      results, HIV testing policy that promotes HIV testing in medical settings and
      among STI patients is needed to facilitate earlier HIV diagnosis in Japan.

PMID- 22581951
TI  - Sexual risk behaviours, condom use and sexually transmitted infection treatment
      seeking behaviours among female sex workers and truck drivers in Uganda.
AB  - We assessed sexual risk behaviours, condom use and sexually transmitted infection
      (STI) treatment-seeking behaviours among truckers and female sex workers (FSWs)
      operating at 12 hotspots along two major transport corridors in Uganda.
      Participants were identified through local contact persons: 261 truckers and 259
      FSWs were interviewed. FSWs reported a mean number of 28 partners in the past 30
      days while truckers reported a mean of seven partners. Ninety-four percent of
      FSWs and 87% of truckers reported condom use in the past month; however, only 21%
      of truckers and 45% of FSWs reported using condoms consistently during that time.
      More than half of truckers (n = 261) and 77% of FSWs (n = 259) reported that they
      suffered from STIs in the past year, and 93% of FSWs and 92.9% of truckers sought
      treatment for STIs in the past year. Of these, 78% of truckers and 86% of FSWs
      sought treatment at least three days following recognition of symptoms. These
      findings suggest that FSWs and truckers engage in high-risk sexual behaviours
      characterized by multiple sexual partnerships, low consistent condom use and
      delayed treatment-seeking behaviours.

PMID- 22581952
TI  - HIV prevalence among men who have sex with men in New Zealand 1985-2009: 25 years
      of public health monitoring.
AB  - Annual population-based estimates of the number of men who have sex with men
      (MSM) with diagnosed HIV infection (HIV prevalence pool), and the proportion of
      all MSM this represents (HIV prevalence), have been insufficiently described over
      the long term. We investigated the dynamic effects of ongoing HIV diagnoses,
      lower mortality due to treatment and growth in the MSM population over time on
      these two epidemic indicators using national HIV/AIDS surveillance data in New
      Zealand, 1985-2009. The diagnosed HIV prevalence pool rose 79% between 1989 and
      1999, and 137% between 1999 and 2009. Estimates of diagnosed HIV prevalence as a
      proportion of MSM were 0.2% of MSM in 1985, and were between 1.5% and 5.0% of MSM
      by 2009. New Zealand continues to have a relatively low-prevalence HIV epidemic
      among MSM; however, the number of MSM living with diagnosed infection is growing
      rapidly 25 years after HIV testing was introduced.

PMID- 22581953
TI  - Survey of lactation suppression in HIV-positive pregnant women.
AB  - The risk of HIV transmission via breastfeeding is well reported. We conducted a
      national survey in the UK to look at the current knowledge and postpartum
      practice of HIV physicians caring for HIV-positive pregnant women. In total, 167
      questionnaires were distributed, 85 (51%) questionnaires were returned. All the
      respondents advised their patients against breastfeeding, 17 (23%) respondents
      routinely prescribed drugs for postpartum lactation suppression and 32 (43%)
      detailed awareness of interactions between antiretroviral therapy and
      dopaminergic lactation suppression agents. Thirteen respondents reported
      awareness of guidance on lactation suppression. The knowledge and use of
      lactation suppression agents appears to be low. However, its use will not only
      reduce postnatal mastitis and breast engorgement but will also help women deal
      with social pressures to breastfeed. Increased use in specific circumstances will
      improve the postnatal care of HIV-positive pregnant women in the UK.

PMID- 22581954
TI  - A survey of the sexual and reproductive health of HIV-positive women in
      Leicester.
AB  - This project reports results from a questionnaire survey of sexual practices,
      contraception use and pregnancy plans in HIV-positive women in Leicester, UK, in
      order to establish the need for a dedicated sexual and reproductive health (SRH)
      clinic. The majority (96%) of women were aware of the benefits of antiretroviral
      therapy (ART) in pregnancy and 39% were planning a future pregnancy. Most (74%)
      used condoms consistently but their use decreased with the addition of another
      contraceptive method. Condoms were mostly obtained from non-National Health
      Service (NHS) settings. Long-acting reversible contraception (LARC) use was
      higher in this group of women than the general population and mainly provided by
      family planning services. A dedicated SRH clinic was thought to be useful by 79%
      of women. Data also identified some limitations of the existing service and need
      to provide holistic and integrated care.

PMID- 22581955
TI  - HIV-associated neurocognitive disorder: rate of referral for neurorehabilitation
      and psychiatric co-morbidity.
AB  - Despite advances in antiretroviral therapy, HIV-infected patients continue to
      present with HIV-associated neurocognitive disorder (HAND) which may be
      associated with significant psychiatric co-morbidity. We audited our patients
      with HAND referred for psychiatric assessment against the National Service
      Framework guidelines that they should receive neurorehabilitation. We found that
      despite these patients posing a risk to themselves and others due to poor insight
      and medication adherence, high rates of psychiatric co-morbidity and severely
      challenging behaviour, few were referred for neurorehabilitation. We recommend
      that clear referral pathways for psychiatric intervention and neurorehabilitation
      are established in HIV treatment centres.

PMID- 22581956
TI  - Medical ward admissions among HIV-positive patients in Winnipeg, Canada, 2003-10.
AB  - Canadian data regarding the characteristics of HIV-positive patients admitted to
      hospital as well as the causes and patterns of admissions remain limited. Chart
      reviews were performed to ascertain admission diagnosis, co-morbidities and CD4
      counts among this sub-population, which had an over-representation of Aboriginal
      persons. Infectious diseases, particularly pneumonia, represent the most common
      admission diagnosis for HIV-positive persons in Winnipeg. Further, individuals
      presenting to hospital often have very low CD4 counts, representing significant
      immune suppression. Earlier HIV diagnosis and treatment in an effort to delay the
      onset of advanced disease and hospitalization is needed.

PMID- 22581957
TI  - Successful therapeutic splenectomy in an HIV patient with relapsing visceral
      leishmaniasis.
AB  - A 43-year-old HIV-positive Ethiopian immigrant presented with persistent
      diarrhoea, hepatosplenomegaly and pancytopaenia. Visceral leishmaniasis was
      diagnosed by multiple gastrointestinal tract biopsies. Blood polymerase chain
      reaction (PCR) was positive for Leishmania donovani. Despite highly active
      antiretroviral therapy (HAART) and multiple courses of antileishmanial
      treatments, including liposomal amphotericin and sodium stibogluconate, the
      patient had multiple relapses. CD4 counts remained at 40-60 cells/uL although
      viral loads were undetectable. Splenectomy resulted in resolution of the
      patient's pancytopaenia and in rising CD4 levels, which enabled a long-lasting
      remission.

PMID- 22581958
TI  - Shared care approach to managing ophthalmological disease in patients with
      positive treponemal serology: a case series.
AB  - Ocular syphilis presenting initially as various manifestations of intraocular
      inflammation is a rare but an important manifestation of syphilis. Ocular
      phenotypes are varied and mimic other infectious and non-infectious ocular
      diseases. Uncertainties exist in optimal management of ocular manifestations of
      syphilis due to a lack of evidence from randomized controlled trials. In this
      article we report seven cases of syphilis representing a spectrum of ophthalmic
      manifestations and highlight key issues around diagnosis and management. We
      underscore the importance of interdisciplinary approach by ophthalmologists and
      genitourinary (GU) physicians in improving the outcome of this subgroup of
      patients in the absence of robust evidence.

PMID- 22581959
TI  - Imiquimod use in adolescents: off-label but effective.
AB  - Genital warts are very common in the under-18 years old population, yet treatment
      with imiquimod is currently off-label. We looked at 50 cases of genital warts in
      patients aged under 18 years who had been treated with Imiquimod to see if this
      treatment was effective, and it was.

PMID- 22581960
TI  - Do not forget to examine the genitals: a case of anal cancer and anogenital
      intraepithelial neoplasia in an immunocompetent man.
AB  - A 46-year-old Caucasian heterosexual male was referred to a dedicated AIN clinic
      from colorectal multidisciplinary meeting (MDM) with AIN 3 following complete
      resection of anal squamous cell carcinoma (SCC). On further questioning, he
      revealed that he also had a lesion on his penis. Histology of the penile lesion
      demonstrated full thickness penile intraepithelial neoplasia (PIN 3). This case
      illustrates the importance of thorough genital examination in patients found to
      have one genital pathology.

PMID- 22581961
TI  - A positive Fast Alcohol Screening Test score may not be associated with sexually
      transmitted infection rates in differing populations.

PMID- 22581962
TI  - Increasing HIV testing in non-genitourinary settings: a follow-up study in
      general practice and a new study in a hospital setting.

PMID- 22581963
TI  - Can self-reported height and weight be used among people living with HIV/AIDS?
AB  - To assess the reliability and validity of self-reported height and weight in
      adults living with HIV/AIDS (ALWHA) we assessed 508 ALWHA of both genders on
      antiretroviral therapy. Height and weight were directly measured in a subsample.
      Sensitivity and specificity analysis were performed to determine the validity of
      self-reported measures. Bland-Altman's method was used to calculate the limits of
      agreement between values while reliability was assessed using intraclass
      coefficients. Regression equations were devised to determine actual measures from
      self-reported values. Mean differences among measured and self-reported weight
      were -0.96 kg for men and -0.54 kg for women. Mean height differences were less
      than 2 cm, yielding good reliability for body mass index (BMI). Overweight (BMI
      >= 25 kg/m(2)) diagnosis sensitivity was 90.6% and specificity was 81.2%.
      Corrected measures determined by regression equations had stronger correlation
      with self-reported values (r > 0.980). Self-reported height and weight showed
      good reliability and validity compared with directly measured height and weight.
      However, measures should be corrected whenever possible to achieve higher
      accuracy.

PMID- 22581964
TI  - Migration/mobility and risk factors for HIV among female sex workers in Andhra
      Pradesh, India: implications for HIV prevention.
AB  - We examined the relation between high mobility/migration (sex work in three or
      more villages/towns within the past year) and HIV risk factors among a sample of
      female sex workers (FSWs) in Andhra Pradesh, India. We recruited FSWs aged >=18
      years (n = 673) through respondent-driven sampling for a survey on HIV risk.
      Adjusted logistic and linear regression models assessed high mobility in relation
      to sexual and physical victimization, sexually transmitted infection (STI)
      symptoms and treatment, condom use and negotiation, number and/or types of sex
      trades, number of clients and number of days worked. Twelve percent (n = 82) of
      FSWs were highly mobile; those with high mobility were more likely to report
      recent HIV risk factors: sexual violence (adjusted odds ratio [AOR] = 5.2; 95%
      confidence interval [CI]: 3.0-8.9), physical violence (AOR = 1.7; 95% CI: 1.1
      2.7), unprotected sex for more money (AOR = 1.7; 95% CI: 1.1-3.0), at least one
      STI symptom (AOR = 1.9; 95% CI: 1.1-3.1), a greater number of vaginal sex trades
      (beta = 3.9, P = 0.003), a greater number of clients (beta = 2.5, P = 0.02) and
      anal sex with clients (AOR = 2.4; 95% CI: 1.4-4.1). Findings from this study
      underscore the violence and HIV-related vulnerability faced by mobile/migrant
      FSWs and highlight the need to inform and tailor related prevention strategies.

PMID- 22581965
TI  - Increased lung cancer mortality among chrysotile asbestos textile workers is more
      strongly associated with exposure to long thin fibres.
AB  - BACKGROUND: Animal data and physical models suggest that the carcinogenicity of
      asbestos fibres is related to their size and shape. OBJECTIVES: To investigate
      the influence of fibre length and diameter on lung cancer risk in workers at
      asbestos textile mills in North Carolina and South Carolina, USA. METHODS: Men
      and women (n=6136) who worked >=30 days in production and were employed between
      1940 and 1973 were enumerated and followed for vital status through 2003. A
      matrix of fibre size-specific exposure estimates was constructed using
      determinations of fibre numbers and dimensions through analysis of 160 historical
      dust samples by transmission electron microscopy. Associations of lung cancer
      mortality with metrics of fibre exposure were estimated by Poisson regression
      with adjustment for age, sex, race and calendar year. RESULTS: Exposure to fibres
      throughout the range of length and diameter was significantly associated with
      increased risk of lung cancer. Models for fibres >5 MUm long and <0.25 MUm in
      diameter provided the best fit to the data, while fibres 5-10 MUm long and <0.25
      MUm in diameter were associated most strongly with lung cancer mortality (log
      rate about 4% per IQR, p<0.001). When indicators of mean fibre length and
      diameter were modelled simultaneously, lung cancer risk increased as fibre length
      increased and diameter decreased. CONCLUSIONS: The findings support the
      hypothesis that the occurrence of lung cancer is associated most strongly with
      exposure to long thin asbestos fibres. The relationship of cancer risk and fibre
      dimensions should be examined in cohorts exposed to other types of fibres.

PMID- 22581966
TI  - Office workers' risk factors for the development of non-specific neck pain: a
      systematic review of prospective cohort studies.
AB  - The purpose of this study was to systematically review prospective cohort studies
      to gain insights into risk factors for the development of non-specific neck pain
      in office workers as well as to assess the strength of evidence. Publications
      were systematically searched from 1980 - March 2011 in several databases. The
      following key words were used: neck pain paired with risk or prognostic factors
      and office or computer or visual display unit or visual display terminal.
      Relevant studies were retrieved and assessed for methodological quality by two
      independent reviewers. The strength of the evidence was based on methodological
      quality and consistency of the results. Five high-quality and two low-quality
      prospective cohort studies investigating the predictive value of 47 individual,
      work-related physical and work-related psychosocial factors for the onset of non
      specific neck pain in office workers were included in this review. Strong
      evidence was found for female gender and previous history of neck complaints to
      be predictors of the onset of neck pain. Interestingly, for a large number of
      factors that have been mentioned in the literature as risk factors for neck pain,
      such as high physical leisure activity, low social support, and high psychosocial
      stress, we found no predictive value for future neck pain in office workers.
      Literature with respect to the development of non-specific neck pain in office
      workers is scant. Only female gender and previous history of neck complaints have
      been identified as risk factors that predict the onset of neck pain.

PMID- 22581967
TI  - The immunogenetics of immune dysregulation, polyendocrinopathy, enteropathy, X
      linked (IPEX) syndrome.
AB  - Immune dysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome
      is a rare disorder in humans caused by germ-line mutations in the FOXP3 gene, a
      master transcriptional regulator for the development of CD4 regulatory T (Treg)
      cells. This T cell subset has global inhibitory functions that maintain immune
      homeostasis and mediate self-tolerance. Treg developmental deficiency or
      dysfunction is a hallmark of IPEX. It leads to severe, multi-organ, autoimmune
      phenomena including enteropathy, chronic dermatitis, endocrinopathy and other
      organ-specific diseases such as anaemia, thrombocytopenia, hepatitis and
      nephritis. In this review, the genetic, immunological and clinical
      characteristics of IPEX syndrome are described, and the impact of heritable
      mutations on the function of Treg cells highlighted.

PMID- 22581968
TI  - A novel defect of peroxisome division due to a homozygous non-sense mutation in
      the PEX11beta gene.
AB  - BACKGROUND: Peroxisomes are organelles that proliferate continuously and play an
      indispensable role in human metabolism. Consequently, peroxisomal gene defects
      can cause multiple, often severe disorders, including the peroxisome biogenesis
      disorders. Currently, 13 different PEX proteins have been implicated in various
      stages of peroxisome assembly and protein import. Defects in any of these
      proteins result in a peroxisome biogenesis disorder. The authors present here a
      novel genetic defect specifically affecting the division of peroxisomes. METHODS:
      The authors have studied biochemical and microscopical peroxisomal parameters in
      cultured patient fibroblasts, sequenced candidate PEX genes and determined the
      consequence of the identified PEX11beta gene defect on peroxisome biogenesis in
      patient fibroblasts at different temperatures. RESULTS: The patient presented
      with congenital cataracts, mild intellectual disability, progressive hearing
      loss, sensory nerve involvement, gastrointestinal problems and recurrent migraine
      like episodes. Although microscopical investigations of patient fibroblasts
      indicated a clear defect in peroxisome division, all biochemical parameters
      commonly used for diagnosing peroxisomal disorders were normal. After excluding
      mutations in all PEX genes previously implicated in peroxisome biogenesis
      disorders, it was found that the defect was caused by a homozygous non-sense
      mutation in the PEX11beta gene. The peroxisome division defect was exacerbated
      when the patient's fibroblasts were cultured at 40 degrees C, which correlated
      with a marked decrease in the expression of PEX11gamma. CONCLUSIONS: This novel
      isolated defect in peroxisome division expands the clinical and genetic spectrum
      of peroxisomal disorders and indicates that peroxisomal defects exist, which
      cannot be diagnosed by standard laboratory investigations.

PMID- 22581969
TI  - First PEX11beta patient extends spectrum of peroxisomal biogenesis disorder
      phenotypes.
AB  - Among the human PEX genes associated with peroxisome biogenesis disorders, only
      the PEX11 family genes had not previously been associated with human disease. A
      new study identifies the first patient with a mutation in PEX11beta. The patient
      presents with symptoms atypical for peroxisome biogenesis disorders. Peroxisomes
      in cells derived from this patient appear enlarged and undivided, complying with
      the role of PEX11 proteins in peroxisome proliferation and division. These new
      findings widen the spectrum of clinical and cellular phenotypes of diseases
      associated with defective peroxisome formation.

PMID- 22581970
TI  - A paradigm shift in the delivery of services for diagnosis of inherited retinal
      disease.
AB  - OBJECTIVES: Current technologies for delivering gene testing are labour-intensive
      and expensive. Over the last 3 years, new high-throughput DNA sequencing
      techniques (next generation sequencing; NGS), with the capability to analyse
      multiple genes or entire genomes, have been rapidly adopted into research. This
      study examines the possibility of incorporating NGS into a clinical UK service
      context. METHODS: The study applied NGS of 105 genes to 50 patients known to be
      affected by inherited forms of blindness in the setting of a UK National Health
      Service-accredited diagnostic molecular genetics laboratory. The study assessed
      the ability of an NGS protocol to identify likely disease-causing genetic
      variants when compared with current methodologies available through UK diagnostic
      laboratories. RESULTS: Conventional testing is only applicable to the minority of
      patients with inherited retinal disease and identifies mutations in fewer than
      one in four of those patients tested. By contrast, the NGS assay is directed at
      all patients with such disorders and identifies disease-causing mutations in 50-
      55%, which is a dramatic increase. This includes patients with apparently
      'sporadic' disease, and those for whom clinical management and prognosis are
      altered as a consequence of defining their disease at a molecular level.
      CONCLUSIONS: The new NGS approach delivers a step change in the diagnosis of
      inherited eye disease, provides precise diagnostic information and extends the
      possibility of targeted treatments including gene therapy. The approach
      represents an exemplar that illustrates the opportunity that NGS provides for
      broadening the availability of genetic testing. The technology will be applied to
      many conditions that are associated with high levels of genetic heterogeneity.

PMID- 22581971
TI  - Mutations in WNT10A are present in more than half of isolated hypodontia cases.
AB  - BACKGROUND: Dental agenesis is the most common, often heritable, developmental
      anomaly in humans. Mutations in MSX1, PAX9, AXIN2 and the ectodermal dysplasia
      genes EDA, EDAR and EDARADD have been detected in familial severe tooth agenesis.
      However, until recently, in the majority of cases (~90%) the genetic factor could
      not be identified, implying that other genes must be involved. Recent insights
      into the role of Wnt10A in tooth development, and the finding of hypodontia in
      carriers of the autosomal recessive disorder, odontooncychodermal dysplasia, due
      to mutations in WNT10A (OMIM 257980; OODD), make WNT10A an interesting candidate
      gene for dental agenesis. METHODS: In a panel of 34 patients with isolated
      hypodontia, the candidate gene WNT10A and the genes MSX1, PAX9, IRF6 and AXIN2
      have been sequenced. The probands all had isolated agenesis of between six and 28
      teeth. RESULTS: WNT10A mutations were identified in 56% of the cases with non
      syndromic hypodontia. MSX1, PAX9 and AXIN2 mutations were present in 3%, 9% and
      3% of the cases, respectively. CONCLUSION: The authors identified WNT10A as a
      major gene in the aetiology of isolated hypodontia. By including WNT10A in the
      DNA diagnostics of isolated tooth agenesis, the yield of molecular testing in
      this condition was significantly increased from 15% to 71%.

PMID- 22581973
TI  - Prostate cancer risk assessment model: a scoring model based on the Swedish
      Family-Cancer Database.
AB  - BACKGROUND: Many prostate cancer (PC) risk assessment models have been developed,
      however almost none include familial history. AIM: To produce a risk assessment
      model for PC based on familial background of related cancers. METHOD: 976 859
      independent index men aged >=30 in year 1998 and their family members in the
      Swedish Family-Cancer Database (FCD2010) were randomly divided into development
      (60%) and validation (40%) datasets (follow-up=10 years). The HR from Cox model
      was used to extrapolate risk scores. Results Specified scores were: for PC in
      situ at age <60 years in index man, 5; for PC at age <60 years in each first
      degree relative (FDR), 15; for PC at age >=60 years in each FDR, 10; for PC at
      age <60 years in each second-degree relative, 5; for breast cancer in each FDR,
      2; for oesophageal carcinoma in situ in index man, 2; and for oesophagus cancer
      in each FDR, 2. Based on the findings, if the milestone age for a PC screening
      programme was 60 years or more, the recommended starting age for the men with the
      score-group 6-10 would be 54 years; score-group 11-15, 52 years; score-group 16
      20, 50 years; score-group 21-25, 44 years; and for the score-group 26+ it should
      start before age 40. The concordance index in development and validation sets was
      0.885 (95% CI 0.883 to 0.888). No significant difference was found between curves
      from development and validation datasets (internally validated using twofold
      validation and bootstrapping). CONCLUSION: Familial history of relevant
      malignancies can be used as risk factors to estimate a man's prior risk of
      developing PC. The prostate cancer risk assessment model could satisfactorily
      assess risk of developing prostate cancer.

PMID- 22581972
TI  - Disruption of RAB40AL function leads to Martin--Probst syndrome, a rare X-linked
      multisystem neurodevelopmental human disorder.
AB  - BACKGROUND AND AIM: Martin--Probst syndrome (MPS) is a rare X-linked disorder
      characterised by deafness, cognitive impairment, short stature and distinct
      craniofacial dysmorphisms, among other features. The authors sought to identify
      the causative mutation for MPS. METHODS AND RESULTS: Massively parallel
      sequencing in two affected, related male subjects with MPS identified a RAB40AL
      (also called RLGP) missense mutation (chrX:102,079,078-102,079,079AC->GA p.D59G;
      hg18). RAB40AL encodes a small Ras-like GTPase protein with one suppressor of
      cytokine signalling box. The p.D59G variant is located in a highly conserved
      region of the GTPase domain between beta-2 and beta-3 strands. Using RT-PCR, the
      authors show that RAB40AL is expressed in human fetal and adult brain and kidney,
      and adult lung, heart, liver and skeletal muscle. RAB40AL appears to be a primate
      innovation, with no orthologues found in mouse, Xenopus or zebrafish. Western
      analysis and fluorescence microscopy of GFP-tagged RAB40AL constructs from
      transiently transfected COS7 cells show that the D59G missense change renders
      RAB40AL unstable and disrupts its cytoplasmic localisation. CONCLUSIONS: This is
      the first study to show that mutation of RAB40AL is associated with a human
      disorder. Identification of RAB40AL as the gene mutated in MPS allows for further
      investigations into the molecular mechanism(s) of RAB40AL and its roles in
      diverse processes such as cognition, hearing and skeletal development.

PMID- 22581974
TI  - Re: predictability of adjuvant trastuzumab benefit in N9831 patients using the
      ASCO/CAP HER2-positivity criteria.

PMID- 22581976
TI  - Type I and Type II errors: what are they and why do they matter?

PMID- 22581977
TI  - Endovenous laser ablation of great saphenous veins.

PMID- 22581980
TI  - MODELING OF GENE REGULATORY PROCESSES BY POPULATION MEDIATED SIGNALING. NEW
      APPLICATIONS OF POPULATION BALANCES.
AB  - Population balance modeling is considered for cell populations in gene regulatory
      processes in which one or more intracellular variables undergo stochastic
      dynamics as determined by Ito stochastic differential equations. This paper
      addresses formulation and computational issues with sample applications to the
      spread of drug resistance among bacterial cells. It is shown that predictions
      from population balances can display qualitative differences from those made with
      single cell models which are usually encountered in the literature. Such
      differences are deemed to be important.

PMID- 22581979
TI  - Cumulative Disadvantage and Health: Long-Term Consequences of Obesity?
AB  - Drawing from cumulative disadvantage theory, the health consequences of obesity
      are considered in light of the accumulation of risk factors over the life course.
      Two forms of compensation are also examined to determine if the risk due to
      obesity is persistent or modifiable. Analyses make use of data from a national
      survey to examine the consequences of obesity on disability among respondents 45
      years of age or older, tracked across 20 years (N = 4,106). Results from tobit
      models indicate that obesity, especially when experienced early in life, is
      consistently related to lower-body disability. The results also show that obesity
      has long-term health consequences during adulthood, altering the life course in
      an enduring way. Compensation was not manifest from risk-factor elimination
      (weight loss), but rather through regular exercise. Although there is evidence
      for long-term consequences of risk factors on health, the findings suggest that
      more attention should be given to compensatory mechanisms in the development of
      cumulative disadvantage theory.

PMID- 22581981
TI  - Outcomes in a Sample of Opiod-Dependent Clients Treated Under California's
      Proposition 36.
AB  - This study evaluated treatment outcomes for the reduction of criminal justice
      involvement and substance use among opioid dependent clients in a therapeutic
      community setting under California's Proposition 36. We compared treatment
      outcomes between those mandated to treatment under Proposition 36 (n = 24) and
      those on probation but not involved in Proposition 36 (n = 61) over 12 months.
      Over time, both groups showed significant improvement on drug use and employment
      measures, were more likely to be involved in job training and less likely to be
      engaged in work activity, and had similar retention in treatment. There was no
      evidence that treatment outcomes were different between the two groups. These
      findings may be helpful in guiding policy makers and clinicians in states where
      similar initiatives are under consideration.

PMID- 22581982
TI  - Mate Availability and Women's Sexual Experiences in China.
AB  - Data from the 1999-2000 Chinese Health and Family Life Survey were merged with
      community-level data from the 1982, 1990, and 2000 Chinese censuses to examine
      the relationship between the local sex ratio (number of men per 100 women) and
      sexual outcomes among women (N = 1,369). Consistent with hypotheses derived from
      demographic-opportunity theory, multilevel logistic regression analyses showed
      that women are more likely to be sexually active, to have had premarital sexual
      intercourse, to have been forced to have sex, and to test positive for a sexually
      transmitted infection when there is a relative abundance of age-matched men in
      their local community. Education, birth cohort, and geographic location also
      emerged as significant predictors of women's sexual experiences.

PMID- 22581983
TI  - The potential of Pathfinder AVHRR data for providing surrogate climatic variables
      across Africa and Europe for epidemiological applications.
AB  - Surface climatic conditions are key determinants of arthropod vector distribution
      and abundance and consequently affect transmission rates of any diseases they may
      carry. Remotely sensed observations by satellite sensors are the only feasible
      means of obtaining regional and continental scale measurements of climate at
      regular intervals for real-time epidemiological applications such as disease
      early warning systems. The potential of Pathfinder AVHRR Land (PAL) data to
      provide surrogate variables for near-surface air temperature and vapour pressure
      deficit (VPD) over Africa and Europe were assessed in this context. For the years
      1988-1990 and 1992, correlations were examined between meteorological ground
      measurements (monthly mean air temperature and VPD(grd)) and variables derived
      from Advanced Very High Resolution Radiometer (AVHRR) data (LST and VPD(sat)).
      The AVHRR indices were derived from both daily and composite PAL data so that
      their relative performance could be determined. Furthermore, the ground
      observations were divided into African and European subsets, so that the relative
      performance of the satellite data at tropical/sub-tropical and temperate
      latitudes could be assessed.Significant correlations were shown between air
      temperature and LST in all months. Temporal variability existed in the strength
      of correlations throughout any twelve-month period, with the pattern of
      variability consistent between years. The adjusted r(2) values increased when
      elevation and the Normalised Difference Vegetation Index (NDVI) were included, in
      addition to LST, as predictor variables of air temperature. Attempts to derive
      monthly estimates of atmospheric moisture availability resulted in an over
      estimation of VPD(sat) compared to ground observations, VPD(grd). The use of
      daily PAL data to derive monthly mean climatic indices was shown to be more
      accurate than those obtained using monthly maximum values from 10-day composite
      data. A subset of the 1992 data was then used to build linear regression models
      for the direct retrieval of monthly mean air temperature from PAL data. The
      accuracy of retrieved estimates was greatest when NDVI was included with LST as
      predictor variables, with root mean square errors varying from 1.83 degrees C to
      3.18  degrees C with a mean of 2.38  degrees C over the twelve months.

PMID- 22581984
TI  - Defining approaches to settlement mapping for public health management in Kenya
      using medium spatial resolution satellite imagery.
AB  - This paper presents an appraisal of satellite imagery types and texture measures
      for identifying and delineating settlements in four Districts of Kenya chosen to
      represent the variation in human ecology across the country. Landsat Thematic
      Mapper (TM) and Japanese Earth Resources Satellite-1 (JERS-1) synthetic aperture
      radar (SAR) imagery of the four districts were obtained and supervised per-pixel
      classifications of image combinations tested for their efficacy at settlement
      delineation. Additional data layers including human population census data, land
      cover, and locations of medical facilities, villages, schools and market centres
      were used for training site identification and validation. For each district, the
      most accurate approach was determined through the best correspondence with known
      settlement and non-settlement pixels. The resulting settlement maps will be used
      in combination with census data to produce medium spatial resolution population
      maps for improved public health planning in Kenya.

PMID- 22581985
TI  - Assessing the accuracy of satellite derived global and national urban maps in
      Kenya.
AB  - Ninety percent of projected global urbanization will be concentrated in low
      income countries (United-Nations, 2004). This will have considerable
      environmental, economic and public health implications for those populations.
      Objective and efficient methods of delineating urban extent are a cross-sectoral
      need complicated by a diversity of urban definition rubrics world-wide. Large
      area maps of urban extents are becoming increasingly available in the public
      domain, as are a wide-range of medium spatial resolution satellite imagery. Here
      we describe the extension of a methodology based on Landsat ETM and Radarsat
      imagery to the production of a human settlement map of Kenya. This map was then
      compared with five satellite imagery-derived, global maps of urban extent at
      Kenya national-level, against an expert opinion coverage for accuracy assessment.
      The results showed the map produced using medium spatial resolution satellite
      imagery was of comparable accuracy to the expert opinion coverage. The five
      global urban maps exhibited a range of inaccuracies, emphasising that care should
      be taken with use of these maps at national and sub-national scale.

PMID- 22581986
TI  - Flexible semiparametric analysis of longitudinal genetic studies by reduced rank
      smoothing.
AB  - In family-based longitudinal genetic studies, investigators collect repeated
      measurements on a trait that changes with time along with genetic markers. Since
      repeated measurements are nested within subjects and subjects are nested within
      families, both the subject-level and measurement-level correlations must be taken
      into account in the statistical analysis to achieve more accurate estimation. In
      such studies, the primary interests include to test for quantitative trait locus
      (QTL) effect, and to estimate age-specific QTL effect and residual polygenic
      heritability function. We propose flexible semiparametric models along with their
      statistical estimation and hypothesis testing procedures for longitudinal genetic
      designs. We employ penalized splines to estimate nonparametric functions in the
      models. We find that misspecifying the baseline function or the genetic effect
      function in a parametric analysis may lead to substantially inflated or highly
      conservative type I error rate on testing and large mean squared error on
      estimation. We apply the proposed approaches to examine age-specific effects of
      genetic variants reported in a recent genome-wide association study of blood
      pressure collected in the Framingham Heart Study.

PMID- 22581987
TI  - Differences in trouble per litre of different alcoholic beverages - A global
      comparison with the GENACIS dataset.
AB  - Different alcoholic beverages are seen as causing more or less trouble, with
      spirits historically often seen as the most troublesome. Differences in the
      "trouble per litre" could reflect differences in the beverages themselves (e.g.,
      faster effect of stronger beverages, additives/contaminants in informal
      beverages), or could reflect characteristics of those drinking each beverage.
      Using two alternative definitions of beverage choice and measures of personal and
      of social consequences of drinking, the paper examines trouble per litre among
      beer, wine and spirits drinkers in 19 different societies represented in the
      GENACIS dataset. There is no general pattern which holds across cultures of more
      or less trouble being associated with a particular beverage type. Wine seems to
      be less associated with trouble than beer or spirits in a number of societies,
      but there are counter-instances in other societies. There is no overall trend
      across cultures in comparing trouble associated with beer and with spirits. In a
      number of societies, drinkers with no predominant beverage report more problems
      than those mainly drinking beer or wine. Controlling for gender and age reduces
      the tilt towards less trouble from wine drinking, particularly for social
      consequences of drinking.

PMID- 22581988
TI  - Reactive and self-regulatory dimensions of temperament: Interactive relations
      with symptoms of general distress and anhedonia.
AB  - Converging evidence indicates that shared temperamental diatheses partly underlie
      the covariance between anxiety and depression. Although developmental
      psychopathology research suggests that self-regulatory temperament (e.g.,
      effortful control or EC) mitigates reactive risks associated with negative
      affectivity (NA) and positive affectivity (PA), and their respective
      counterparts, behavioral inhibition- and activation sensitivity (BIS and BAS), no
      studies have established EC's protective effects in adulthood. This study
      examined concurrent relations between temperament and distress symptoms shared by
      anxiety and depression, and anhedonic symptoms unique to depression, in young
      adults. Anticipated two- and three-way interactions emerged supporting EC's
      moderating effect between reactive temperament (i.e., high BIS and low BAS) and
      both symptom dimensions. However, no interactive relations emerged between
      symptoms and NA, PA, and EC.

PMID- 22581989
TI  - Tsetse Fly Control in Kenya's Spatially and Temporally Dynamic Control
      Reservoirs: A Cost Analysis.
AB  - Human African trypanosomiasis (HAT) and animal African trypanosomiasis (AAT) are
      significant health concerns throughout much of sub-Saharan Africa. Funding for
      tsetse fly control operations has decreased since the 1970s, which has in turn
      limited the success of campaigns to control the disease vector. To maximize the
      effectiveness of the limited financial resources available for tsetse control,
      this study develops and analyzes spatially and temporally dynamic tsetse
      distribution maps of Glossina subgenus Morsitans populations in Kenya from
      January 2002 to December 2010, produced using the Tsetse Ecological Distribution
      Model. These species distribution maps reveal seasonal variations in fly
      distributions. Such variations allow for the identification of "control
      reservoirs" where fly distributions are spatially constrained by fluctuations in
      suitable habitat and tsetse population characteristics. Following identification
      of the control reservoirs, a tsetse management operation is simulated in the
      control reservoirs using capital and labor control inputs from previous studies.
      Finally, a cost analysis, following specific economic guidelines from existing
      tsetse control analyses, is conducted to calculate the total cost of a nationwide
      control campaign of the reservoirs compared to the cost of a nationwide campaign
      conducted at the maximum spatial extent of the fly distributions from January
      2002 to December 2010. The total cost of tsetse management within the reservoirs
      sums to $14,212,647, while the nationwide campaign at the maximum spatial extent
      amounts to $33,721,516. This savings of $19,508,869 represents the importance of
      identifying seasonally dynamic control reservoirs when conducting a tsetse
      management campaign, and, in the process, offers an economical means of fly
      control and disease management for future program planning.

PMID- 22581990
TI  - INTERNATIONAL MIGRATION AND THE EDUCATION OF CHILDREN: EVIDENCE FROM LIMA, PERU.
AB  - The issue of whether emigration has consequences for the education of children
      who remain behind in the country of origin occupies an increasingly prominent
      place in the agendas of both scholars and policy makers. The conventional wisdom
      is that the emigration of family members may benefit children by relaxing budget
      constraints through remittances that can be used to cover educational expenses.
      However, the empirical evidence on the overall effect of migration is
      inconclusive. This is due in part to a substantive emphasis on remittances in the
      literature, as well as the inability of some studies to deal satisfactorily with
      the endogeneity of household migration decisions in comparing outcomes across
      migrant and non-migrant households. Using Peruvian data from the Latin American
      Migration Project (LAMP), we apply an innovative instrumental variable technique
      to evaluate the overall effect of migration on educational attainment and
      schooling disruption among the children of immigrants. In contrast to
      conventional wisdom, our results suggest that a higher household risk of
      immigration has deleterious consequences for the education of children who remain
      behind.

PMID- 22581991
TI  - Home and Where the Heart Is: Marriage Timing and Joint Home Purchase.
AB  - This article evaluates the relationship between the timing of marriage and the
      purchase of a jointly owned home among Swedish cohabiting couples. Data for this
      analysis come from the Swedish Housing and Life Course Cohort Study (N = 1,596
      couples; 2,006 cohabiting spells). The author develops models to proxy for
      simultaneity and intentions and test hypotheses about positive and negative and
      long- and short-run relationships between the two life-course events. The author
      uses a novel modeling approach, allowing for differences in the risk before,
      concurrently and after the conditioning event. Results indicate a positive
      relationship between marriage and joint home purchase and suggest the possibility
      of an ordering of events: For some couples, formalizing their union through
      marriage may be a prerequisite for a joint home purchase.

PMID- 22581992
TI  - Rituximab in steroid-resistant nephrotic syndrome in children: a (false) glimmer
      of hope?

PMID- 22581993
TI  - Human AKI and heme oxygenase-1.

PMID- 22581995
TI  - A photo shoot of proteinuria: zebrafish models of inducible podocyte damage.

PMID- 22581994
TI  - Rituximab in children with resistant idiopathic nephrotic syndrome.
AB  - Idiopathic nephrotic syndrome resistant to standard treatments remains a
      therapeutic dilemma in pediatric nephrology. To test whether the anti-CD20
      monoclonal antibody rituximab may benefit these patients, we conducted an open
      label, randomized, controlled trial in 31 children with idiopathic nephrotic
      syndrome unresponsive to the combination of calcineurin inhibitors and
      prednisone. All children continued prednisone and calcineurin inhibitors at the
      doses prescribed before enrollment, and one treatment group received two doses of
      rituximab (375 mg/m(2) intravenously) as add-on therapy. The mean age was 8 years
      (range, 2-16 years). Rituximab did not reduce proteinuria at 3 months (change, 
      12% [95% confidence interval, -73% to 110%]; P=0.77 in analysis of covariance
      model adjusted for baseline proteinuria). Additional adjustment for previous
      remission and interaction terms (treatment by baseline proteinuria and treatment
      by previous remission) did not change the results. In conclusion, these data do
      not support the addition of rituximab to prednisone and calcineurin inhibitors in
      children with resistant idiopathic nephrotic syndrome.

PMID- 22581996
TI  - Calcium deficiency reduces circulating levels of FGF23.
AB  - Fibroblast growth factor (FGF) 23 inhibits calcitriol production, which could
      exacerbate calcium deficiency or hypocalcemia unless calcium itself modulates
      FGF23 in this setting. In Wistar rats with normal renal function fed a diet low
      in both calcium and vitamin D, the resulting hypocalcemia was associated with low
      FGF23 despite high parathyroid hormone (PTH) and high calcitriol levels. FGF23
      correlated positively with calcium and negatively with PTH. Addition of high
      dietary phosphorus to this diet increased FGF23 except in rats with hypocalcemia
      despite high PTH levels. In parathyroidectomized rats, an increase in dietary
      calcium for 10 days increased serum calcium, with an associated increase in
      FGF23, decrease in calcitriol, and no change in phosphorus. Also in
      parathyroidectomized rats, FGF23 increased significantly 6 hours after
      administration of calcium gluconate. Taken together, these results suggest that
      hypocalcemia reduces the circulating concentrations of FGF23. This decrease in
      FGF23 could be a response to avoid a subsequent reduction in calcitriol, which
      could exacerbate hypocalcemia.

PMID- 22581997
TI  - Increasing Opportunities for Inner-City Youth: The Feasibility of an Economic
      Empowerment Model in East Harlem and the South Bronx, New York.
AB  - Youth of color are disproportionately likely to grow-up in poor, disadvantaged
      neighborhoods characterized by high levels of psychosocial stressors and
      inadequate supportive resources. Poverty and racial minority status correlate
      with an increased risk of high-school dropout, teen pregnancy, substance abuse,
      and sexually transmitted infections (STIs). Given these trends, child welfare
      researchers are developing various interventions to increase the protective
      resources and social opportunities available to youth of color. This article
      reports results of a preliminary, qualitative study that investigated the
      feasibility and acceptability of an economic empowerment intervention in the
      South Bronx and East Harlem, New York. Using focus groups and brief
      questionnaires with youth and their parents/guardians (N=24 dyads), we explored
      attitudes toward youth educational savings accounts, financial planning classes,
      and mentorship for inner-city youth. Findings indicate a strong interest in an
      economic empowerment intervention among adolescents and their caregivers in these
      communities. These findings have implications for the design of larger-scale
      research programs that aim to improve inner-city youth's socio-economic wellbeing
      using economic empowerment models.

PMID- 22581998
TI  - Maternal Re-Partnering and New-Partner Fertility: Associations with Nonresident
      Father Investments in Children.
AB  - Research suggests that paternal re-partnering and new-partner fertility are
      associated with decreased nonresident father investments in children. Few
      studies, however, have examined the influence of maternal re-partnering and new
      partner births on nonresident father investments. We use data from the National
      Longitudinal Survey of Youth to examine associations of maternal re-partnering
      (through cohabitation or marriage with a new partner) and new-partner births with
      nonresident father visitation and child support payments. Results suggest that
      maternal re-partnering is associated with a decrease in both yearly father-child
      contact and child support received by the mother. New-partner fertility for
      mothers who are co-residing with a partner is associated with an additional
      decrease in monthly father-child contact, but does not have an additional
      influence on yearly father-child contact or child support receipt.

PMID- 22581999
TI  - An Exploratory Study of Staff Capture at the South African Inspectorate of
      Prisons.
AB  - When prison inspectorates are co-opted or "captured" by those they are
      monitoring, their ability to bring transparency, accountability, and a human
      rights culture to prisons becomes harder. Using survey data from 102 staff at the
      South African Judicial Inspectorate of Prisons (JIOP), this exploratory study
      measured the severity of staff capture (i.e. they were not protecting the
      exclusive interests of prisoners) and potential correlates of capture. Overall,
      study participants exhibited significant levels of capture with Ordinary Least
      Squares regression indicating higher levels of capture among staff that were
      African, thought about someday working for the Department of Correctional
      Services, felt powerless when prison officials ignored them, and if prison
      officials respected their work (p's < .05). Length of JIOP employment was not
      associated with capture. These findings suggest that the JIOP's policy of not
      renewing many staffs' three year contracts could ironically be putting them at
      risk for capture.

PMID- 22582000
TI  - The Revised Commitment Inventory: Psychometrics and Use with Unmarried Couples.
AB  - The Commitment Inventory (Stanley & Markman, 1992) measures interpersonal
      commitment (dedication) and constraint commitment. Since it was first published,
      substantial revisions have been made, but there are no published data on the
      psychometric properties of the new version. Further, little information is
      available on measuring commitment for unmarried couples. This study examined the
      psychometric properties of the Commitment Inventory in 320 premarital or
      cohabiting couples (N = 640). Dyadic confirmatory factor analyses revealed that
      the hypothesized factor structure of six constraint subscales and one dedication
      subscale fit the data well for both men and women. Internal consistency
      coefficients were within acceptable range for most subscales. Within-couple
      correlations as well as correlations among subscales and with relationship
      quality, negative communication, and religiosity are presented. Implications for
      future research are discussed.

PMID- 22582001
TI  - Use of Community and School Mental Health Services by Custodial Grandchildren.
AB  - We examined patterns and predictors of the perceived need, use, and unmet need
      for mental health services by custodial grandchildren within both the school
      based and community-based delivery sectors. Data were self-reported by a national
      sample of 610 custodial grandmothers providing full-time care to grandchildren
      ages 6 to 17 in the absence of biological parents. Although overlapping use of
      services across both sectors was common, the overall use of school-based services
      (51%) was higher than that of community-based services (37%). Using theAndersen
      Social and Behavioral Model (1995) the following shared predictors of mental
      health service use across both sectors by custodial grand-families emerged:
      grandchildren's externalizing symptoms, having other grandchildren in the
      household with medical or psychiatric diagnoses and corresponding use of services
      in the other sector. Predictors were largely the same regardless of whether
      analyses were conducted with families recruited by probability or convenience
      based sampling methods. Findings suggest the necessity to coordinate and
      integrate the availability and implementation of mental health services for
      custodial grandchildren across different delivery sectors.

PMID- 22582002
TI  - A comparison of drill- and communication-based treatment for aphasia.

PMID- 22582003
TI  - Water Diffusion In And Out Of The beta-Barrel Of GFP and The Fast Maturing
      Fluorescent Protein, TurboGFP.
AB  - The chromophore of fluorescent proteins is formed by an internal cyclization of
      the tripeptide 65SYG67 fragment and a subsequent oxidation. The oxidation is slow
      - the kinetics of this step is presumably improved in fast maturing GFPs. Water
      molecules can aid in the chromophore formation. We have used 50ns molecular
      dynamics simulations of the mature and immature forms of avGFP and TurboGFP to
      examine the diffusion of water molecules in-and-out of the protein beta-barrel.
      Most crystal structures of GFPs have well-structured waters within hydrogen
      bonding distance of Glu222 and Arg96. It has been proposed that they have an
      important role in chromophore formation. Stable waters are found in similar
      positions in all simulations conducted. The simulations confirm the existence of
      a pore that leads to the chromophore in the rapidly maturing TurboGFP; decreased
      water diffusion upon chromophore formation; and increased water diffusion due to
      the pore formation.

PMID- 22582004
TI  - A Comparison of EPI Sampling, Probability Sampling, and Compact Segment Sampling
      Methods for Micro and Small Enterprises.
AB  - Finding an efficient method for sampling micro- and small-enterprises (MSEs) for
      research and statistical reporting purposes is a challenge in developing
      countries, where registries of MSEs are often nonexistent or outdated. This lack
      of a sampling frame creates an obstacle in finding a representative sample of
      MSEs. This study uses computer simulations to draw samples from a census of
      businesses and non-businesses in the Tshwane Municipality of South Africa, using
      three different sampling methods: the traditional probability sampling method,
      the compact segment sampling method, and the World Health Organization's Expanded
      Programme on Immunization (EPI) sampling method. Three mechanisms by which the
      methods could differ are tested, the proximity selection of respondents, the at
      home selection of respondents, and the use of inaccurate probability weights. The
      results highlight the importance of revisits and accurate probability weights,
      but the lesser effect of proximity selection on the samples' statistical
      properties.

PMID- 22582005
TI  - Workflow and radiation safety implications of (18)F-FDG PET/CT scans for
      radiotherapy planning.
AB  - The use of (18)F-FDG PET/CT for radiotherapy planning may lead to better tumor
      volume definition. Reproduction of the patient's position when setting up an
      (18)F-FDG PET/CT scan for radiotherapy planning is more accurate if a radiation
      therapist is involved. The aim of this study was to compare setup time and staff
      radiation dose between radiation therapists and nuclear medicine technologists.
      METHODS: Forty patients with newly diagnosed head and neck or non-small cell lung
      cancer were prospectively recruited into this study. Twenty patients (10 with
      head and neck cancer and 10 with non-small cell lung cancer) underwent (18)F-FDG
      PET/CT for radiotherapy planning, and 20 patients (10 with head and neck cancer
      and 10 with non-small cell lung cancer) underwent (18)F-FDG PET/CT for staging.
      Setup time was measured, and a radiation monitor recorded the highest dose
      (MUSv/h) to staff during setup. RESULTS: For radiation therapists, the mean setup
      time for a lung scan (in min:s) was 5:22 +/- 2:11 (range, 2:22-9:23), with a
      highest dose of 4.94 +/- 3.78 MUSv (range, 2.02-15.23 MUSv), and the mean setup
      time for a head and neck scan was 4:49 +/- 1:45 (range, 2:03-8:21), with a
      highest dose of 3.93 +/- 1.45 MUSv (range, 1.19-6.83 MUSv). For nuclear medicine
      technologists, the mean setup time for a lung scan was 1:58 +/- 0:24 (range, 1:17
      2:38), with a highest dose of 3.30 +/- 1.28 MUSv (range, 1.92-5.47 MUSv), and the
      mean setup time for a head and neck scan was 2:12 +/- 0:38 (range, 1:03-3:16),
      with a highest dose of 3.10 +/- 1.78 MUSv (range, 1.56-7.49 MUSv). CONCLUSION:
      This study showed that setup time and operator radiation dose were greater for
      radiation therapists setting up planning (18)F-FDG PET/CT scans than for nuclear
      medicine technologists setting up routine (18)F-FDG PET/CT scans. These results
      have implications for scheduling of radiotherapy planning PET/CT; however, the
      additional radiation dose was not considered to be significant.

PMID- 22582006
TI  - Small-animal PET: what is it, and why do we need it?
AB  - Small-animal PET refers to imaging of animals such as rats and mice using
      dedicated PET scanners. Small-animal PET has been used extensively in modern
      biomedical research. It provides a quantitative measure of the 3-dimensional
      distribution of a radiopharmaceutical administered to a live subject
      noninvasively. In this article, we will discuss the operational and technical
      aspects of small-animal PET; make some comparisons between small-animal PET and
      human PET systems; identify the challenges of, opportunities for, and ultimate
      limitations in applying small-animal PET; and discuss some representative small
      animal PET applications. Education objectives: After reading this article, the
      technologist will be able to explain the requirements and benefits of small
      animal PET in biomedical research, describe the design and general
      characteristics of a small-animal PET system, list and describe some of the
      challenges of imaging small animals, and discuss several small-animal PET
      applications.

PMID- 22582007
TI  - Prolonged Exposure Therapy for PTSD among Individuals in a Residential Substance
      Use Treatment Program: A Case Series.
AB  - Clients with co-occurring posttraumatic stress disorder (PTSD) and substance use
      disorders present a unique challenge for clinicians in substance use treatment
      settings. Substance dependent individuals with PTSD tend to improve less during
      substance use treatment and relapse more quickly following abstinence attempts
      compared to those without PTSD. Recent scientific efforts have focused on
      understanding the potential benefit of providing PTSD treatment concurrent with
      substance use treatment. The current case study describes 4 individuals with PTSD
      in a residential substance use facility who received prolonged exposure therapy
      for treatment of PTSD, in addition to the substance use treatment. These
      individuals completed 9 bi-weekly 60-minute sessions of prolonged exposure, as
      well as in vivo and imaginal exposure homework between sessions. None of the
      clients met criteria for PTSD at the end of treatment, with these gains being
      maintained at 3- and 6-months post-treatment. Additionally, the clients did not
      relapse in response to undergoing exposure therapy. Implications for delivery of
      PTSD treatment in substance use treatment facilities are discussed.

PMID- 22582008
TI  - Recall Latencies, Confidence, and Output Positions of True and False Memories:
      Implications for Recall and Metamemory Theories.
AB  - Recall latency, recall accuracy rate, and recall confidence were examined in free
      recall as a function of recall output serial position using a modified Deese
      Roediger-McDermott paradigm to test a strength-based theory against the dual
      retrieval process theory of recall output sequence. The strength theory predicts
      the item output sequence to be in the descending order of memory strength. The
      dual-retrieval process theory postulates two phases in a free recall, a first
      direct access phase in which items are output verbatim in the weakest-to
      strongest order (cognitive triage) and a second reconstructive phase in which
      reconstructed items are output in the strongest-to-weakest order. In three
      experiments, all three indicators of memory strength (latency, accuracy, and
      confidence) consistently showed a descending-strength order of recall both for
      true and false memories. Additionally, false memory was found to be output in two
      phases and subjects' confidence judgment of their own memory to be unaccountable
      by retrieval fluency (recall latency).

PMID- 22582009
TI  - A Run-time System for Efficient Execution of Scientific Workflows on Distributed
      Environments.
AB  - Scientific workflow systems have been introduced in response to the demand of
      researchers from several domains of science who need to process and analyze
      increasingly larger datasets. The design of these systems is largely based on the
      observation that data analysis applications can be composed as pipelines or
      networks of computations on data. In this work, we present a runtime support
      system that is designed to facilitate this type of computation in distributed
      computing environments. Our system is optimized for data-intensive workflows, in
      which efficient management and retrieval of data, coordination of data processing
      and data movement, and check-pointing of intermediate results are critical and
      challenging issues. Experimental evaluation of our system shows that linear
      speedups can be achieved for sophisticated applications, which are implemented as
      a network of multiple data processing components.

PMID- 22582010
TI  - Intermittent neural synchronization in Parkinson's disease.
AB  - Motor symptoms of Parkinson's disease are related to the excessive synchronized
      oscillatory activity in the beta frequency band (around 20Hz) in the basal
      ganglia and other parts of the brain. This review explores the dynamics and
      potential mechanisms of these oscillations employing ideas and methods from
      nonlinear dynamics. We present extensive experimental documentation of the
      relevance of synchronized oscillations to motor behavior in Parkinson's disease,
      and we discuss the intermittent character of this synchronization. The reader is
      introduced to novel time-series analysis techniques aimed at the detection of the
      fine temporal structure of intermittent phase locking observed in the brains of
      parkinsonian patients. Modeling studies of brain networks are reviewed, which may
      describe the observed intermittent synchrony, and we discuss what these studies
      reveal about brain dynamics in Parkinson's disease. The parkinsonian brain
      appears to exist on the boundary between phase-locked and nonsynchronous
      dynamics. Such a situation may be beneficial in the healthy state, as it may
      allow for easy formation and dissociation of transient patterns of synchronous
      activity which are required for normal motor behavior. Dopaminergic degeneration
      in Parkinson's disease may shift the brain networks closer to this boundary,
      which would still permit some motor behavior while accounting for the associated
      motor deficits. Understanding the mechanisms of the intermittent synchrony in
      Parkinson's disease is also important for biomedical engineering since efficient
      control strategies for suppression of pathological synchrony through deep brain
      stimulation require knowledge of the dynamics of the processes subjected to
      control.

PMID- 22582011
TI  - The heliosphere's interstellar interaction: no bow shock.
AB  - As the Sun moves through the local interstellar medium, its supersonic, ionized
      solar wind carves out a cavity called the heliosphere. Recent observations from
      the Interstellar Boundary Explorer (IBEX) spacecraft show that the relative
      motion of the Sun with respect to the interstellar medium is slower and in a
      somewhat different direction than previously thought. Here, we provide combined
      consensus values for this velocity vector and show that they have important
      implications for the global interstellar interaction. In particular, the velocity
      is almost certainly slower than the fast magnetosonic speed, with no bow shock
      forming ahead of the heliosphere, as was widely expected in the past.

PMID- 22582012
TI  - Vitamin K2 is a mitochondrial electron carrier that rescues pink1 deficiency.
AB  - Human UBIAD1 localizes to mitochondria and converts vitamin K(1) to vitamin K(2).
      Vitamin K(2) is best known as a cofactor in blood coagulation, but in bacteria it
      is a membrane-bound electron carrier. Whether vitamin K(2) exerts a similar
      carrier function in eukaryotic cells is unknown. We identified Drosophila
      UBIAD1/Heix as a modifier of pink1, a gene mutated in Parkinson's disease that
      affects mitochondrial function. We found that vitamin K(2) was necessary and
      sufficient to transfer electrons in Drosophila mitochondria. Heix mutants showed
      severe mitochondrial defects that were rescued by vitamin K(2), and, similar to
      ubiquinone, vitamin K(2) transferred electrons in Drosophila mitochondria,
      resulting in more efficient adenosine triphosphate (ATP) production. Thus,
      mitochondrial dysfunction was rescued by vitamin K(2) that serves as a
      mitochondrial electron carrier, helping to maintain normal ATP production.

PMID- 22582014
TI  - Astronomy. Evidence of things not seen.

PMID- 22582013
TI  - Secreted kinase phosphorylates extracellular proteins that regulate
      biomineralization.
AB  - Protein phosphorylation is a fundamental mechanism regulating nearly every aspect
      of cellular life. Several secreted proteins are phosphorylated, but the kinases
      responsible are unknown. We identified a family of atypical protein kinases that
      localize within the Golgi apparatus and are secreted. Fam20C appears to be the
      Golgi casein kinase that phosphorylates secretory pathway proteins within S-x-E
      motifs. Fam20C phosphorylates the caseins and several secreted proteins
      implicated in biomineralization, including the small integrin-binding ligand, N
      linked glycoproteins (SIBLINGs). Consequently, mutations in Fam20C cause an
      osteosclerotic bone dysplasia in humans known as Raine syndrome. Fam20C is thus a
      protein kinase dedicated to the phosphorylation of extracellular proteins.

PMID- 22582015
TI  - Microbiology. Virulence or competition?

PMID- 22582017
TI  - Geophysics. A rogue earthquake off Sumatra.

PMID- 22582016
TI  - Regulated virulence controls the ability of a pathogen to compete with the gut
      microbiota.
AB  - The virulence mechanisms that allow pathogens to colonize the intestine remain
      unclear. Here, we show that germ-free animals are unable to eradicate Citrobacter
      rodentium, a model for human infections with attaching and effacing bacteria.
      Early in infection, virulence genes were expressed and required for pathogen
      growth in conventionally raised mice but not germ-free mice. Virulence gene
      expression was down-regulated during the late phase of infection, which led to
      relocation of the pathogen to the intestinal lumen where it was outcompeted by
      commensals. The ability of commensals to outcompete C. rodentium was determined,
      at least in part, by the capacity of the pathogen and commensals to grow on
      structurally similar carbohydrates. Thus, pathogen colonization is controlled by
      bacterial virulence and through competition with metabolically related
      commensals.

PMID- 22582018
TI  - The detection and characterization of a nontransiting planet by transit timing
      variations.
AB  - The Kepler mission is monitoring the brightness of ~150,000 stars, searching for
      evidence of planetary transits. As part of the Hunt for Exomoons with Kepler
      (HEK) project, we report a planetary system with two confirmed planets and one
      candidate planet discovered with the publicly available data for KOI-872. Planet
      b transits the host star with a period P(b) = 33.6 days and exhibits large
      transit timing variations indicative of a perturber. Dynamical modeling uniquely
      detects an outer nontransiting planet c near the 5:3 resonance (P(c) = 57.0 days)
      with a mass 0.37 times that of Jupiter. Transits of a third planetary candidate
      are also found: a 1.7-Earth radius super-Earth with a 6.8-day period. Our
      analysis indicates a system with nearly coplanar and circular orbits, reminiscent
      of the orderly arrangement within the solar system.

PMID- 22582019
TI  - Evidence for Purinergic Receptors in Vestibular Dark Cell and Strial Marginal
      Cell Epithelia of Gerbil.
AB  - Purinergic receptors have been found to modulate ion transport in several types
      of epithelial cells as well as excitable cells. It was of interest to determine
      whether vestibular dark cells and strial marginal cells contain purinergic
      receptors in either the apicalor basolateral membrane which modulate
      transepithelial ion transport. Vestibular dark cell and strial marginal cell
      epithelia were mounted in a micro-Ussing chamber for the measurement of the
      transepithelial voltage and resistance from which the equivalent short circuit
      current (I(sc)) was obtained. The apical and basolateral sides were independently
      perfused with adenosine and adenosine 5'-triphosphate (ATP). Adenosine (10(-5) M)
      had no effect on I(sc) at either the apical or basolateral side of vestibular
      dark cells and strial marginal cells, suggesting either the absence of P(1)
      receptors or the absence of coupling of P(1) receptors to vectorial ion transport
      by these epithelia. Apical perfusion of ATP (10(-8) to 10(-4) M) caused a
      decrease in I(sc) of both vestibular dark cells and strial marginal cells. Apical
      perfusion of the nucleotides uridine 5'-triphosphate (UTP), 2-methylthioadenosine
      triphosphate (2-meS-ATP), adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS) and
      alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-meth-ATP) caused
      qualitatively similar responses with different magnitudes of response. The
      sequence of the magnitude of response of each compound at 10(-6) or 10(-5) M was
      assessed from the fractional change of I(sc). The sequence for vestibular dark
      cells was UTP = ATP = ATPgammaS ? 2-meS-ATP > alpha,beta-meth-ATP, and for strial
      marginal cells it was UTP = ATP ? 2-meS-ATP, corresponding to the sequence for
      the P(2U) receptor. The effect of agonist on the apical membrane was reduced by
      the antagonist 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) but not
      cibacron blue or suramin. DIDS in the absence of exogenous purinergic agonist
      caused a sustained increase in I(sc). The effect of ATP on the apical membrane
      was greater in the absence of divalent cations. Basolateral perfusion of ATP led
      to a biphasic response of I(sc) in vestibular dark cell and strial marginal cell
      epithelia, consisting of an initial rapid increase followed by a slower decrease.
      Perfusion of the perilymphatic surface of the stria vascularis (basal cell layer)
      with ATP had no acute effect on I(sc). The initial increase of I(sc) in
      vestibular dark cell epithelium during basolateral perfusion had a sequence of 2
      meS-ATP > ATP ? UTP = alpha,beta-meth-ATP = ATPgammaS, corresponding to the
      sequence for the P(2Y) receptor. Subsequently, the agonists caused a sustained
      decrease in I(sc) with a sequence of ATPgammaS > 2-meS-ATP > ATP > UTP
      >alpha,beta-meth-ATP. This sequence is most simply interpreted as the result of
      the coexistence of P(2U) and P(2Y) receptors in the basolateral membrane. Both
      the increase and decrease of I(sc) by ATP at the basolateral membrane were
      reduced by the antagonist suramin. These findings provide evidence for the
      regulation of transepithelial ion transport by P(2U) receptors in the apical
      membrane and by coexisting P(2U) and P(2Y) receptors in the basolateral membrane
      of K(+)-secretory epithelial cells in the inner ear and are consistent with the
      hypothesis that the apical receptors are part of an autocrine negative feedback
      system in these cells.

PMID- 22582020
TI  - I(sK) Channel in Strial Marginal Cells. Voltage-Dependence, Ion-Selectivity,
      Inhibition by 293B and Sensitivity to Clofilium.
AB  - Strial marginal cells (SMC) and vestibular dark cells (VDC) are known to secrete
      K(+) into endolymph. Slowly-activating, voltage-dependent K(+) channels
      (KCNQ1/KCNE1; IsK; min K) have been identified in the apical membrane of these
      cells. Several experimental maneuvers known to increase or decrease
      transepithelial K(+) secretion have been found in VDC to change the current
      through these channels in the same ways. In both SMC and VDC the kinetics of
      activation and deactivation resemble those of the I(sK) channel exogenously
      expressed in Xenopus oocytes and endogenous to heart myocytes. The present study
      sought evidence that this current is indeed carried by I(sK) channels and that
      this current is the basis for transepithelial K(+) secretion. Both on-cell macro
      patch recordings of the apical membrane and perforated-patch whole-cell
      recordings were made on SMC from gerbil in order to measure macroscopic cell
      currents. The on-cell current was found to 1) be K(+)-selective, 2) have a cation
      permeability sequence of K(+) ~ Rb(+) > Cs(+) >> Li(+) = Na(+), 3) be activated
      with a time constant of 1764 +/- 413 ms by voltage steps from 0 to +40 mV, 4) be
      deactivated with a time constant of 324 +/- 57 ms by voltage steps from 0 to -40
      mV and 5) be reduced 84 +/- 5% by bumetanide (10(-5) M), an inhibitor of K(+)
      secretion. The single-channel conductance of the apical currents in the
      homologous VDC was estimated by fluctuation analysis to be 1.6 pS. The potent
      inhibitor of I(sK) channels, chromanol 293B (10(-5) M), reduced the whole-cell
      current in SMC by 72 +/- 10 %. Clofilium (10(-4) M), a putative I(sK) channel
      inhibitor known to have additional non-specific effects, led to a stimulation of
      both on-cell (by 598 +/- 177%) and whole-cell (by 162 +/- 18%) currents in gerbil
      SMC but to a decrease of whole-cell currents (by 39 +/- 12%) in rat SMC. Taken
      together with other findings reviewed here, these results strongly argue that the
      slowly-activating, voltage-dependent conductance in the apical membrane of SMC is
      the I(sK) channel and provide additional evidence for the poor specificity of
      clofilium.

PMID- 22582021
TI  - Co-occurring Psychiatric and Substance Dependence Disorders as Predictors of
      Parolee Time to Rearrest.
AB  - An estimated 500,000-plus people are on parole each year, many with serious co
      occurring psychiatric and substance use disorders. Using cross sectional, self
      report data this study examined the relationships between parolee time to
      rearrest, serious mental illnesses, and substance dependency (n = 1,121).
      Regression analyses indicated that after controlling for demographic and criminal
      justice variables, parolees with serious psychiatric and substance dependence
      disorders were rearrested faster than non-dually diagnosed parolees (p < .05). An
      explanation is that compared with parolees without dual diagnoses, parole
      violations by dually diagnosed parolees are detected and punished more quickly
      because of closer parole supervision.

PMID- 22582022
TI  - A Prospective Examination of the Association of Stimulant Medication History and
      Drug Use Outcomes among Community Samples of ADHD Youths.
AB  - A continuing debate in the child psychopathology literature is the extent to
      which pharmacotherapy for children with attention-deficit/hyperactivity disorder
      (ADHD), in particular stimulant treatment, confers a risk of subsequent drug
      abuse. If stimulant treatment for ADHD contributes to drug abuse, then the risk
      versus therapeutic benefits of such treatment is greatly affected. We have
      prospectively followed an ADHD sample (N = 149; 81% males) for approximately 15
      years, beginning at childhood (ages 8 to 10 years) and continuing until the
      sample has reached young adulthood (ages 22 to 24 years). The sample was
      originally recruited via an epidemiologically derived community procedure, and
      all youths were diagnosed with ADHD during childhood. We report on the
      association of childhood psychostimulant medication and subsequent substance use
      disorders and tobacco use. The substance use outcomes were based on data
      collected at three time points when the sample was in late adolescence and young
      adulthood (age range approximately 18 to 22 years old). We did not find evidence
      to support that childhood treatment with stimulant medication, including the
      course of stimulant medication, was associated with any change in risk for
      adolescent or young adulthood substance use disorders and tobacco use. These
      results from a community-based sample extend the growing body of literature based
      on clinically derived samples indicating that stimulant treatment does not create
      a significant risk for subsequent substance use disorders.

PMID- 22582023
TI  - Midlife sexuality among Thai adults: Adjustment to aging in the Thai family
      context.
AB  - The objective of the study is to assess views of age related changes in sexual
      behavior among married Thai adults age 53 to 57. Results are viewed in the
      context of life course theory. In-depth interviews were conducted with 44 Thai
      adults in Bangkok and the four regions of Thailand. Topics covered include
      changing sexual behavior with age, adjustment to this change, gender differences
      in behavior, attitudes toward commercial sex and other non-marital sexual
      partners, and condom use. Most respondents were aware of this change and saw a
      decrease in sexual activity and desire more often among women compared to men. At
      the same time, many respondents viewed sexuality as important to a marriage. Some
      respondents accepted the decrease in sexual activity and focused more on work,
      family and temple activities. Thai Buddhism was seen as an important resource for
      people who were dealing with changes due to aging. Other persons turned to other
      partners including both commercial and non-commercial partners. The influence of
      the HIV epidemic that began in the 1990s was seen in concerns about disease
      transmission with extramarital partners and consequent attitudes toward condom
      use. The acceptability of extramarital partners in the family and community
      ranged from acceptance to strong disapproval of extramarital relationships.

PMID- 22582024
TI  - Histone Deacetylase Inhibitors and Mithramycin A Impact a Similar Neuroprotective
      Pathway at a Crossroad between Cancer and Neurodegeneration.
AB  - Mithramycin A (MTM) and histone deacetylase inhibitors (HDACi) are effective
      therapeutic agents for cancer and neurodegenerative diseases. MTM is a FDA
      approved aureolic acid-type antibiotic that binds to GC-rich DNA sequences and
      interferes with Sp1 transcription factor binding to its target sites (GC box).
      HDACi, on the other hand, modulate the activity of class I and II histone
      deacetylases. They mediate their protective function, in part, by regulating the
      acetylation status of histones or transcription factors, including Sp1, and in
      turn chromatin accessibility to the transcriptional machinery. Because these two
      classes of structurally and functionally diverse compounds mediate similar
      therapeutic functions, we investigated whether they act on redundant or
      synergistic pathways to protect neurons from oxidative death. Non-protective
      doses of each of the drugs do not synergize to create resistance to oxidative
      death suggesting that these distinct agents act via a similar pathway.
      Accordingly, we found that protection by MTM and HDACi is associated with
      diminished expression of the oncogene, Myc and enhanced expression of a tumor
      suppressor, p21(waf1/cip1). We also find that neuroprotection by MTM or Myc
      knockdown is associated with downregulation of class I HDAC levels. Our results
      support a model in which the established antitumor drug MTM or canonical HDACi
      act via distinct mechanisms to converge on the downregulation of HDAC levels or
      activity respectively. These findings support the conclusion that an imbalance in
      histone acetylase and HDAC activity in favor of HDACs is key not only for
      oncogenic transformation, but also neurodegeneration.

PMID- 22582025
TI  - Beta-Cell Injury in Ncb5or-null Mice is Exacerbated by Consumption of a High-Fat
      Diet.
AB  - NADH-cytochrome b5 oxidoreductase (Ncb5or) in endoplasmic reticulum (ER) is
      involved in fatty acid metabolism, and Ncb5or(-/-) mice fed standard chow (SC)
      are insulin-sensitive but weigh less than wild type (WT) littermates. Ncb5or(-/-)
      mice develop hyperglycemia at about age 7 weeks due to beta-cell dysfunction and
      loss associated with saturated fatty acid accumulation and manifestations of ER
      and oxidative stress. Here we report that when Ncb5or(-/-) mice born to
      heterozygous mothers fed a high fat (HF) diet continue to ingest HF, they weigh
      as much as SC-fed WT at age 5 weeks. By age 7 weeks, diabetes mellitus develops
      in all HF-fed vs. 68% of SC-fed Ncb5or(-/-) mice. Islet beta-cell content in age
      5-week Ncb5or(-/-) mice fed HF for 7 days is lower (53%) than for those fed SC
      (63%), and both are lower than for WT (75%, SC, vs. 69%, HF). Islet transcript
      levels for markers of mitochondrial biogenesis (PGC-1alpha) and ER stress
      (ATF6alpha) are higher in Ncb5or(-/-) than WT mice but not significantly affected
      by diet. Consuming a HF diet exacerbates Ncb5or(-/-) beta-cell accumulation of
      intracellular saturated fatty acids and increases the frequency of ER distention
      from 11% (SC) to 47% (HF), thus accelerates beta-cell injury in Ncb5or(-/-) mice.

PMID- 22582026
TI  - Correlates of schizophrenia spectrum disorders in children and adolescents cared
      for in community settings.
AB  - BACKGROUND: This study examined the prevalence and correlates of schizophrenia
      spectrum disorders (SSD) among a national sample of 9006 children.  METHODS:
      Clinician-assigned diagnoses were used to divide the sample into two groups:
      children with SSD and children with other Axis I disorders.  RESULTS: Three
      percent of the sample had a SSD diagnosis. African American (OR=1.71, 95% CI:
      1.11, 2.65) and Hispanic race/ethnicity (OR=1.96, 95% CI: 1.31, 2.94), a greater
      number of comorbid psychiatric diagnoses (three diagnoses, OR=2.22, 95% CI: 1.49,
      3.31), a history of attempting suicide (OR=1.45; 95% CI: 1.05, 2.02), and past
      residential treatment (OR=1.59; 95% CI: 1.11, 2.28) were all associated with
      increased odds of SSD diagnosis.  CONCLUSIONS: Although schizophrenia spectrum
      disorders in youth are rare, children with these disorders present with a
      distinct risk profile that may inform service planning and delivery and assist in
      identifying individuals early in the course of their illness.

PMID- 22582027
TI  - DRUG MARKET RECONSTITUTION AFTER HURRICANE KATRINA: LESSONS FOR LOCAL DRUG ABUSE
      CONTROL INITIATIVES.
AB  - Hurricane Katrina accomplished what no law enforcement initiative could ever
      achieve: It completely eradicated the New Orleans drug market. However, Katrina
      did little to eliminate the demand for drugs. This article documents the process
      of the drug market reconstitution that occurred 2005-2008 based on in-depth
      interviews and focus groups with predominately low-income drug users and sellers.
      Before Katrina, the drug market was largely characterized by socially-bonded
      participants involved with corporate style distribution. After Katrina, a violent
      freelance market emerged. The conclusion draws recommendations for law
      enforcement for dealing with drug markets after a major disaster.This article
      uses New Orleans as a case study to chart the process of drug market
      reconstitution following an extreme disaster, namely Hurricane Katrina. On August
      29, 2005, Hurricane Katrina made landfall and engulfed the New Orleans area,
      overwhelming levees and causing extensive flooding and destruction across the
      city. The storm generated 30- to 40-foot waves, which demolished many cities and
      small towns in Southern Mississippi and Alabama and caused considerable wind
      damage further inland. Although the hurricane eye missed central New Orleans by
      about 30 miles, the wave action in Lake Pontchartrain caused several levees to
      break and flood most of eastern New Orleans, which was under sea level. The storm
      had an impact on practically all New Orleans residents and almost destroyed New
      Orleans (Cooper & Block, 2006; Levitt & Whitaker, 2009; Lee, 2006).Our research
      focused on the impact of this storm on the drug markets in New Orleans. Katrina
      destroyed the physical environment and organizational structure that sustained
      the drug trade, yet drug use and sales did not disappear. During and soon after
      the storm, improvised sales and distribution organizations provided a wide range
      of illicit drugs to users (see Dunlap, Johnson, Kotarba, & Fackler, 2009; Dunlap
      & Golub, 2010; Dunlap, Johnson & Morse, 2007). This article examines the next
      historical period, the continuation of drug use among those returning to New
      Orleans and the rebuilding of drug market structures. The analysis provides a
      short review of drug markets before Katrina. Our main focus is the reconstitution
      process during the three years following the disaster. We pay special attention
      to street-level dealers and the end users' lived experiences in primarily poorer
      neighborhoods, illustrating elements of continuity and change as various actors
      reconstituted New Orleans' drug market.

PMID- 22582028
TI  - Photomorphogenesis.
AB  - As photoautotrophs, plants are exquisitely sensitive to their light environment.
      Light affects many developmental and physiological responses throughout plants'
      life histories. The focus of this chapter is on light effects during the crucial
      period of time between seed germination and the development of the first true
      leaves. During this time, the seedling must determine the appropriate mode of
      action to best achieve photosynthetic and eventual reproductive success. Light
      exposure triggers several major developmental and physiological events. These
      include: growth inhibition and differentiation of the embryonic stem (hypocotyl);
      maturation of the embryonic leaves (cotyledons); and establishment and activation
      of the stem cell population in the shoot and root apical meristems. Recent
      studies have linked a number of photoreceptors, transcription factors, and
      phytohormones to each of these events.

PMID- 22582029
TI  - Shade avoidance.
AB  - The presence of neighboring vegetation modifies the light environment experienced
      by plants, generating signals that are perceived by phytochromes and
      cryptochromes. These signals cause large changes in plant body form and function,
      including enhanced growth of the hypocotyl and petioles, a more erect position of
      the leaves and early flowering in Arabidopsis thaliana. Collectively, these so
      called shade-avoidance responses tend to reduce the degree of current or future
      shade by neighbors. Shade light signals increase the abundance of PHYTOCHROME
      INTERACTING FACTOR 4 (PIF4) and PIF5 proteins, promote the synthesis and
      redirection of auxin, favor the degradation of DELLA proteins and increase the
      expression of auxin, gibberellins and brassinosteroid-promoted genes, among other
      events downstream the photoreceptors. Selectively disrupting these events by
      genetic or pharmacological approaches affects shade-avoidance responses with an
      intensity that depends on the developmental context and the environment. Shade
      avoidance responses provide a model to investigate the signaling networks used by
      plants to take advantage of the cues provided by the environment to adjust to the
      challenges imposed by the environment itself.

PMID- 22582031
TI  - Routine Microsecond Molecular Dynamics Simulations with AMBER on GPUs. 1.
      Generalized Born.
AB  - We present an implementation of generalized Born implicit solvent all-atom
      classical molecular dynamics (MD) within the AMBER program package that runs
      entirely on CUDA enabled NVIDIA graphics processing units (GPUs). We discuss the
      algorithms that are used to exploit the processing power of the GPUs and show the
      performance that can be achieved in comparison to simulations on conventional CPU
      clusters. The implementation supports three different precision models in which
      the contributions to the forces are calculated in single precision floating point
      arithmetic but accumulated in double precision (SPDP), or everything is computed
      in single precision (SPSP) or double precision (DPDP). In addition to
      performance, we have focused on understanding the implications of the different
      precision models on the outcome of implicit solvent MD simulations. We show
      results for a range of tests including the accuracy of single point force
      evaluations and energy conservation as well as structural properties pertainining
      to protein dynamics. The numerical noise due to rounding errors within the SPSP
      precision model is sufficiently large to lead to an accumulation of errors which
      can result in unphysical trajectories for long time scale simulations. We
      recommend the use of the mixed-precision SPDP model since the numerical results
      obtained are comparable with those of the full double precision DPDP model and
      the reference double precision CPU implementation but at significantly reduced
      computational cost. Our implementation provides performance for GB simulations on
      a single desktop that is on par with, and in some cases exceeds, that of
      traditional supercomputers.

PMID- 22582033
TI  - Improving Internal Peptide Dynamics in the Coarse-Grained MARTINI Model: Toward
      Large-Scale Simulations of Amyloid- and Elastin-like Peptides.
AB  - We present an extension of the coarse-grained MARTINI model for proteins and
      apply this extension to amyloid- and elastin-like peptides. Atomistic simulations
      of tetrapeptides, octapeptides, and longer peptides in solution are used as a
      reference to parametrize a set of pseudodihedral potentials that describe the
      internal flexibility of MARTINI peptides. We assess the performance of the
      resulting model in reproducing various structural properties computed from
      atomistic trajectories of peptides in water. The addition of new dihedral angle
      potentials improves agreement with the contact maps computed from atomistic
      simulations significantly. We also address the question of which parameters
      derived from atomistic trajectories are transferable between different lengths of
      peptides. The modified coarse-grained model shows reasonable transferability of
      parameters for the amyloid- and elastin-like peptides. In addition, the improved
      coarse-grained model is also applied to investigate the self-assembly of beta
      sheet forming peptides on the microsecond time scale. The octapeptides SNNFGAIL
      and (GV)(4) are used to examine peptide aggregation in different environments, in
      water, and at the water-octane interface. At the interface, peptide adsorption
      occurs rapidly, and peptides spontaneously aggregate in favor of stretched
      conformers resembling beta-strands.

PMID- 22582034
TI  - Optimizing Populations of SAI Tactile Mechanoreceptors to Enable Activities of
      Daily Living.
AB  - At present, the dense network of peripheral afferents between finger and brain
      and the large size of engineered sensors preclude the recreation of biologically
      observed afferent populations. This work uses a validated computational model of
      cutaneous skin and tactile afferents to evaluate sparse populations in performing
      tasks required in activities of daily living. Using a model (3D finite element
      representation of fingertip skin, linear bi-phasic transduction function, and
      leaky-integrate-and-fire neuronal model), we systematically varied populations of
      tactile receptors in dimensions of density (100, 45, 20, and 10 sensors/cm(2))
      and size (diameter 0.1, 0.2, 0.5, and 1.0 mm) to determine if a given modeled
      population can discriminate spheres and cylinders representative of objects used
      in activities of daily living. Using a scoring system which allows for direct
      comparisons between the populations, our results indicate that a population must
      have at least 20 sensors per cm(2) to maintain response resolution in these
      activities of daily living and that larger-sized sensors do not degrade response
      resolution.

PMID- 22582032
TI  - The Structure, Thermodynamics and Solubility of Organic Crystals from Simulation
      with a Polarizable Force Field.
AB  - An important unsolved problem in materials science is prediction of the
      thermodynamic stability of organic crystals and their solubility from first
      principles. Solubility can be defined as the saturating concentration of a
      molecule within a liquid solvent, where the physical picture is of solvated
      molecules in equilibrium with their solid phase. Despite the importance of
      solubility in determining the oral bioavailability of pharmaceuticals, prediction
      tools are currently limited to quantitative structure-property relationships that
      are fit to experimental solubility measurements. For the first time, we describe
      a consistent procedure for the prediction of the structure, thermodynamic
      stability and solubility of organic crystals from molecular dynamics simulations
      using the polarizable multipole AMOEBA force field. Our approach is based on a
      thermodynamic cycle that decomposes standard state solubility into the sum of
      solid-vapor sublimation and vapor-liquid solvation free energies [Formula: see
      text], which are computed via the orthogonal space random walk (OSRW) sampling
      strategy. Application to the n-alkylamides series from aeetamide through
      octanamide was selected due to the dependence of their solubility on both amide
      hydrogen bonding and the hydrophobic effect, which are each fundamental to
      protein structure and solubility. On average, the calculated absolute standard
      state solubility free energies are accurate to within 1.1 kcal/mol. The
      experimental trend of decreasing solubility as a function of n-alkylamide chain
      length is recapitulated by the increasing stability of the crystalline state and
      to a lesser degree by decreasing favorability of solvation (i.e. the hydrophobic
      effect). Our results suggest that coupling the polarizable AMOEBA force field
      with an orthogonal space based free energy algorithm, as implemented in the
      program Force Field X, is a consistent procedure for predicting the structure,
      thermodynamic stability and solubility of organic crystals.

PMID- 22582030
TI  - Carotenoid biosynthesis in Arabidopsis: a colorful pathway.
AB  - Plant carotenoids are a family of pigments that participate in light harvesting
      and are essential for photoprotection against excess light. Furthermore, they act
      as precursors for the production of apocarotenoid hormones such as abscisic acid
      and strigolactones. In this review, we summarize the current knowledge on the
      genes and enzymes of the carotenoid biosynthetic pathway (which is now almost
      completely elucidated) and on the regulation of carotenoid biosynthesis at both
      transcriptional and post-transcriptional levels. We also discuss the relevance of
      Arabidopsis as a model system for the study of carotenogenesis and how metabolic
      engineering approaches in this plant have taught important lessons for carotenoid
      biotechnology.

PMID- 22582035
TI  - Mixed Methods for the Interpretation of Longitudinal Gerontologic Data: Insights
      From Philosophical Hermeneutics.
AB  - This article's main objective is to demonstrate that data analysis, including
      quantitative data analysis, is a process of interpretation involving basic
      hermeneutic principles that philosophers have identified in the interpretive
      process as applied to other, mainly literary, creations. Such principles include
      a version of the hermeneutic circle, an insistence on interpretive
      presuppositions, and a resistance to reducing the discovery of truth to the
      application of inductive methods. The importance of interpretation becomes
      especially evident when qualitative and quantitative methods are combined in a
      single clinical research project and when the data being analyzed are
      longitudinal. Study objectives will be accomplished by showing that three major
      hermeneutic principles make practical methodological contributions to an
      insightful, illustrative mixed methods analysis of a qualitative study of changes
      in functional disability over time embedded in the Precipitating Events Project-a
      major longitudinal, quantitative study of functional disability among older
      persons. Mixed methods, especially as shaped by hermeneutic insights such as the
      importance of empathetic understanding, are potentially valuable resources for
      scientific investigations of the experience of aging: a practical aim of this
      article is to articulate and demonstrate this contention.

PMID- 22582037
TI  - 22q11.2 Distal Deletion Syndrome: Description of a New Case with Truncus
      Arteriosus Type 2 and Review.
AB  - 22q11.2 deletion syndrome is mainly characterized by conotruncal congenital heart
      defects, velopharyngeal insufficiency, hypocalcemia and a characteristic
      craniofacial appearance. The etiology in the majority of patients is a 3-Mb
      recurrent deletion in region 22q11.2. Nevertheless, recently some cases of
      infrequent deletions with various sizes have been reported with a different
      phenotype. We report on a patient with congenital heart disease (truncus
      arteriosus type 2) in whom a de novo 1.3-Mb 22q11.2 deletion was detected by
      array comparative genomic hybridization. The deletion described corresponds to an
      atypical and distal deletion which spans low copy repeat (LCR) 4 and is
      associated with breakpoint sites that do not correspond to known LCRs of 22q11.2.
      We examine the clinical phenotype of our case and compare our findings with those
      published in the literature. The most prevalent clinical features in this type of
      deletion are a history of prematurity, pre-natal and post-natal growth
      retardation, slight facial dysmorphic features, microcephaly and developmental
      delay, with a speech defect in particular. These are clearly different from those
      found in the classic 22q11.2 deletion syndrome, and we believe that the main
      differential diagnosis should be with Silver-Russel syndrome. In our case we
      observe the cardiac phenotype with truncus arteriosus communis usually seen in
      the classic 22q11.2 deletion syndrome, and so far associated with the TBX1 gene.
      Significantly, however, TBX1 is not included in our patient's deletion. The
      possible roles of a position effect or other genes are discussed.

PMID- 22582036
TI  - Adrenomedullin Function in Vascular Endothelial Cells: Insights from Genetic
      Mouse Models.
AB  - Adrenomedullin is a highly conserved peptide implicated in a variety of
      physiological processes ranging from pregnancy and embryonic development to tumor
      progression. This review highlights past and present studies that have
      contributed to our current appreciation of the important roles adrenomedullin
      plays in both normal and disease conditions. We provide a particular emphasis on
      the functions of adrenomedullin in vascular endothelial cells and how
      experimental approaches in genetic mouse models have helped to drive the field
      forward.

PMID- 22582039
TI  - Psychophysical properties of odor processing can be quantitatively described by
      relative action potential latency patterns in mitral and tufted cells.
AB  - Electrophysiological and population imaging data in rodents show that olfactory
      bulb (OB) activity is profoundly modulated by the odor sampling process while
      behavioral experiments indicate that odor discrimination can occur within a
      single sniff. This paper addresses the question of whether action potential (AP)
      latencies occurring across the mitral and tufted cell (M/TC) population within an
      individual sampling cycle could account for the psychophysical properties of odor
      processing. To determine this we created an OB model (50,000 M/TCs) exhibiting
      hallmarks of published in vivo properties and used a template-matching algorithm
      to assess stimulus separation. Such an AP latency-based scheme showed high
      reproducibility and sensitivity such that odor stimuli could be reliably
      separated independent of concentration. As in behavioral experiments we found
      that very dissimilar odors ("A vs. B") were accurately and rapidly discerned
      while very similar odors (binary mixtures, 0.4A/0.6B vs. 0.6A/0.4B) required up
      to 90 ms longer. As in lesion studies we find that AP latency-based
      representation is rather insensitive to disruption of large regions of the OB.
      The AP latency-based scheme described here, therefore, captures both temporal and
      psychophysical properties of olfactory processing and suggests that the onset
      patterns of M/TC activity in the OB represent stimulus specific features of
      olfactory stimuli.

PMID- 22582038
TI  - Auditory object salience: human cortical processing of non-biological action
      sounds and their acoustic signal attributes.
AB  - Whether viewed or heard, an object in action can be segmented as a distinct
      salient event based on a number of different sensory cues. In the visual system,
      several low-level attributes of an image are processed along parallel
      hierarchies, involving intermediate stages wherein gross-level object form and/or
      motion features are extracted prior to stages that show greater specificity for
      different object categories (e.g., people, buildings, or tools). In the auditory
      system, though relying on a rather different set of low-level signal attributes,
      meaningful real-world acoustic events and "auditory objects" can also be readily
      distinguished from background scenes. However, the nature of the acoustic signal
      attributes or gross-level perceptual features that may be explicitly processed
      along intermediate cortical processing stages remain poorly understood. Examining
      mechanical and environmental action sounds, representing two distinct non
      biological categories of action sources, we had participants assess the degree to
      which each sound was perceived as object-like versus scene-like. We re-analyzed
      data from two of our earlier functional magnetic resonance imaging (fMRI) task
      paradigms (Engel et al., 2009) and found that scene-like action sounds
      preferentially led to activation along several midline cortical structures, but
      with strong dependence on listening task demands. In contrast, bilateral foci
      along the superior temporal gyri (STG) showed parametrically increasing
      activation to action sounds rated as more "object-like," independent of sound
      category or task demands. Moreover, these STG regions also showed parametric
      sensitivity to spectral structure variations (SSVs) of the action sounds-a
      quantitative measure of change in entropy of the acoustic signals over time-and
      the right STG additionally showed parametric sensitivity to measures of mean
      entropy and harmonic content of the environmental sounds. Analogous to the visual
      system, intermediate stages of the auditory system appear to process or extract a
      number of quantifiable low-order signal attributes that are characteristic of
      action events perceived as being object-like, representing stages that may begin
      to dissociate different perceptual dimensions and categories of every-day, real
      world action sounds.

PMID- 22582040
TI  - Visual categorization and the parietal cortex.
AB  - The primate brain is adept at rapidly grouping items and events into functional
      classes, or categories, in order to recognize the significance of stimuli and
      guide behavior. Higher cognitive functions have traditionally been considered the
      domain of frontal areas. However, increasing evidence suggests that parietal
      cortex is also involved in categorical and associative processes. Previous work
      showed that the parietal cortex is highly involved in spatial processing,
      attention, and saccadic eye movement planning, and more recent studies have found
      decision-making signals in lateral intraparietal area (LIP). We recently found
      that a subdivision of parietal cortex, LIP, reflects learned categories for
      multiple types of visual stimuli. Additionally, a comparison of categorization
      signals in parietal and frontal areas found stronger and earlier categorization
      signals in parietal cortex arguing that, in trained animals, parietal abstract
      association or category signals are unlikely to arise via feedback from
      prefrontal cortex (PFC).

PMID- 22582041
TI  - Minimalist approach to perceptual interactions.
AB  - WORK AIMED AT STUDYING SOCIAL COGNITION IN AN INTERACTIONIST PERSPECTIVE OFTEN
      ENCOUNTERS SUBSTANTIAL THEORETICAL AND METHODOLOGICAL DIFFICULTIES: identifying
      the significant behavioral variables; recording them without disturbing the
      interaction; and distinguishing between: (a) the necessary and sufficient
      contributions of each individual partner for a collective dynamics to emerge; (b)
      features which derive from this collective dynamics and escape from the control
      of the individual partners; and (c) the phenomena arising from this collective
      dynamics which are subsequently appropriated and used by the partners. We propose
      a minimalist experimental paradigm as a basis for this conceptual discussion: by
      reducing the sensory inputs to a strict minimum, we force a spatial and temporal
      deployment of the perceptual activities, which makes it possible to obtain a
      complete recording and control of the dynamics of interaction. After presenting
      the principles of this minimalist approach to perception, we describe a series of
      experiments on two major questions in social cognition: recognizing the presence
      of another intentional subject; and phenomena of imitation. In both cases, we
      propose explanatory schema which render an interactionist approach to social
      cognition clear and explicit. Starting from our earlier work on perceptual
      crossing we present a new experiment on the mechanisms of reciprocal recognition
      of the perceptual intentionality of the other subject: the emergent collective
      dynamics of the perceptual crossing can be appropriated by each subject. We then
      present an experimental study of opaque imitation (when the subjects cannot see
      what they themselves are doing). This study makes it possible to characterize
      what a properly interactionist approach to imitation might be. In conclusion, we
      draw on these results, to show how an interactionist approach can contribute to a
      fully social approach to social cognition.

PMID- 22582042
TI  - Neuroimaging of voice hearing in non-psychotic individuals: a mini review.
AB  - Auditory verbal hallucinations (AVH) or "voices" are a characteristic symptom of
      schizophrenia, but can also be observed in healthy individuals in the general
      population. As these non-psychotic individuals experience AVH in the absence of
      other psychiatric symptoms and medication-use they provide an excellent model to
      study AVH in isolation. Indeed a number of studies used this approach and
      investigated brain structure and function in non-psychotic individuals with AVH.
      These studies showed that increased sensitivity of auditory areas to auditory
      stimulation and aberrant connectivity of language production and perception areas
      is associated with AVH. This is in concordance with investigations that observed
      prominent activation of these areas during the state of AVH. Moreover, while
      effortful attention appears not to be related to AVH, individuals prone to
      hallucinate seem to have an enhanced attention bias to auditory stimuli which may
      stem from aberrant activation of the anterior cingulated regions. Furthermore, it
      was observed that decreased cerebral dominance for language and dopamine
      dysfunction, which are consistently found in schizophrenia, are most likely not
      specifically related to AVH as these abnormalities were absent in healthy voice
      hearers. Finally, specific aspects of AVH such as voluntary control may be
      related to the timing of the supplementary motor area and language areas in the
      experience of AVH.

PMID- 22582043
TI  - Does the brain know who is at the origin of what in an imitative interaction?
AB  - Brain correlates of the sense of agency have recently received increased
      attention. However, the explorations remain largely restricted to the study of
      brains in isolation. The prototypical paradigm used so far consists of
      manipulating visual perception of own action while asking the subject to draw a
      distinction between self- versus externally caused action. However, the recent
      definition of agency as a multifactorial phenomenon combining bottom-up and top
      down processes suggests the exploration of more complex situations. Notably there
      is a need of accounting for the dynamics of agency in a two-body context where we
      often experience the double faceted question of who is at the origin of what in
      an ongoing interaction. In a dyadic context of role switching indeed, each
      partner can feel body ownership, share a sense of agency and altogether alternate
      an ascription of the primacy of action to self and to other. To explore the brain
      correlates of these different aspects of agency, we recorded with dual EEG and
      video set-ups 22 subjects interacting via spontaneous versus induced imitation
      (II) of hand movements. The differences between the two conditions lie in the
      fact that the roles are either externally attributed (induced condition) or
      result from a negotiation between subjects (spontaneous condition). Results
      demonstrate dissociations between self- and other-ascription of action primacy in
      delta, alpha and beta frequency bands during the condition of II. By contrast a
      similar increase in the low gamma frequency band (38-47 Hz) was observed over the
      centro-parietal regions for the two roles in spontaneous imitation (SI). Taken
      together, the results highlight the different brain correlates of agency at play
      during live interactions.

PMID- 22582044
TI  - Aldose reductase, oxidative stress, and diabetic mellitus.
AB  - Diabetes mellitus (DM) is a complex metabolic disorder arising from lack of
      insulin production or insulin resistance (Diagnosis and classification of
      diabetes mellitus, 2007). DM is a leading cause of morbidity and mortality in the
      developed world, particularly from vascular complications such as
      atherothrombosis in the coronary vessels. Aldose reductase (AR; ALR2; EC
      1.1.1.21), a key enzyme in the polyol pathway, catalyzes nicotinamide adenosine
      dinucleotide phosphate-dependent reduction of glucose to sorbitol, leading to
      excessive accumulation of intracellular reactive oxygen species (ROS) in various
      tissues of DM including the heart, vasculature, neurons, eyes, and kidneys. As an
      example, hyperglycemia through such polyol pathway induced oxidative stress, may
      have dual heart actions, on coronary blood vessel (atherothrombosis) and
      myocardium (heart failure) leading to severe morbidity and mortality (reviewed in
      Heather and Clarke, 2011). In cells cultured under high glucose conditions, many
      studies have demonstrated similar AR-dependent increases in ROS production,
      confirming AR as an important factor for the pathogenesis of many diabetic
      complications. Moreover, recent studies have shown that AR inhibitors may be able
      to prevent or delay the onset of cardiovascular complications such as
      ischemia/reperfusion injury, atherosclerosis, and atherothrombosis. In this
      review, we will focus on describing pivotal roles of AR in the pathogenesis of
      cardiovascular diseases as well as other diabetic complications, and the
      potential use of AR inhibitors as an emerging therapeutic strategy in preventing
      DM complications.

PMID- 22582045
TI  - Feasibility and dosimetry studies for 18F-NOS as a potential PET
      radiopharmaceutical for inducible nitric oxide synthase in humans.
AB  - Nitric oxide (NO), the end product of the inducible form of NO synthase (iNOS),
      is an important mediator of a variety of inflammatory diseases. Therefore, a
      radiolabeled iNOS radiopharmaceutical for assessing iNOS protein concentration as
      a marker for its activity would be of value to the study and treatment of NO
      related diseases. We recently synthesized an (18)F-radiolabeled analog of the
      reversible NOS inhibitor, 2-amino-4-methylpyridine ((18)F-NOS), and confirmed its
      utility in a murine model of lung inflammation. To determine its potential for
      use in humans, we measured (18)F-NOS myocardial activity in patients after
      orthotopic heart transplantation (OHT) and correlated it with pathologic
      allograft rejection, tissue iNOS levels, and calculated human radiation
      dosimetry. METHODS: Two groups were studied-a kinetic analysis group and a
      dosimetry group. In the kinetic analysis group, 10 OHT patients underwent dynamic
      myocardial (18)F-NOS PET/CT, followed by endomyocardial biopsy. Myocardial (18)F
      NOS PET was assessed using volume of distribution; standardized uptake values at
      10 min; area under the myocardial moment curve (AUMC); and mean resident time at
      5, 10, and 30 min after tracer injection. Tissue iNOS levels were measured by
      immunohistochemistry. In the dosimetry group, the biodistribution and radiation
      dosimetry were calculated using whole-body PET/CT in 4 healthy volunteers and 12
      OHT patients. The combined time-activity curves were used for residence time
      calculation, and organ doses were calculated with OLINDA. RESULTS: Both AUMC at
      10 min (P < 0.05) and tissue iNOS (P < 0.0001) were higher in patients exhibiting
      rejection than in those without rejection. Moreover, the (18)F-NOS AUMC at 10 min
      correlated positively with tissue iNOS at 10 min (R(2) = 0.42, P < 0.05). (18)F
      NOS activity was cleared by the hepatobiliary system. The critical organ was the
      bladder wall, with a dose of 95.3 MUGy/MBq, and an effective dose of 15.9
      MUSv/MBq was calculated. CONCLUSION: Myocardial (18)F-NOS activity is increased
      in organ rejection (a condition associated with increased iNOS levels) and
      correlates with tissue iNOS measurements with acceptable radiation exposure.
      Although further modifications to improve the performance of (18)F-NOS are
      needed, these data show the feasibility of PET of iNOS in the heart and other
      tissues.

PMID- 22582046
TI  - PET of HER2-positive pulmonary metastases with 18F-ZHER2:342 affibody in a murine
      model of breast cancer: comparison with 18F-FDG.
AB  - Targeted therapies often depend on the expression of the target present in the
      tumor. This expression can be difficult to ascertain in widespread metastases.
      (18)F-FDG PET/CT, although sensitive, is nonspecific for particular tumor
      markers. Here, we compare the use of a human epidermal growth factor receptor 2
      (HER2)-specific (18)F-Z(HER2)(:342)-Affibody and (18)F-FDG in HER2-expressing
      pulmonary metastases in a murine model of breast cancer. METHODS: The lung
      metastasis model was established by intravenous injection of MDA-MB-231(HER2)-Luc
      human breast cancer cells into the tail vein. Bioluminescence imaging was used to
      evaluate metastasis progression. Uptake of (18)F-Z(HER2)(:342)-Affibody and (18)F
      FDG was confirmed by coregistration of the PET images with MR and CT images. At
      the end of the study, the presence of neoplastic cells and HER2 expression in
      lung tissues, and distribution of the tracer, were assessed ex vivo by
      immunohistochemistry and autoradiography. RESULTS: (18)F-Z(HER2)(:342)-Affibody
      successfully targeted HER2-positive lesions in the lung and allowed detection of
      metastases as early as 9 wk after injection of cells. In contrast, (18)F-FDG
      uptake was often masked by surrounding inflammatory changes and was nonspecific
      for HER2 expression. HER2 expression at a cellular level correlated well with
      tracer uptake on autoradiography. CONCLUSION: (18)F-Z(HER2)(:342)-Affibody is a
      promising tracer for evaluation of HER2 status of breast cancer metastases and is
      more specific for detecting HER2-positive lesions than (18)F-FDG.

PMID- 22582047
TI  - 18F-FDG PET/CT has a high impact on patient management and provides powerful
      prognostic stratification in the primary staging of esophageal cancer: a
      prospective study with mature survival data.
AB  - The aim of this study is to evaluate the incremental staging information,
      management impact, and prognostic stratification of PET/CT in the primary staging
      of esophageal cancer in a cohort of patients with mature survival data. METHODS:
      Between July 2002 and June 2005, 139 consecutive patients with newly diagnosed
      esophageal cancer underwent conventional staging investigations (CSI), followed
      by PET/CT. Disease stage was classified according to the American Joint Committee
      on Cancer staging system (6th edition) and grouped as stage I-IIA, stage IIB-III,
      and stage IV reflecting broad groupings that determine therapeutic choice.
      Validation of results was performed when PET/CT and CSI stage groups were
      discordant and in those patients where PET/CT changed management. Management
      impact was determined by comparing prospectively recorded pre-PET/CT management
      plans with post-PET/CT management plans. Survival after follow-up of at least 5 y
      in patients was analyzed using the Kaplan-Meier product limit method and the Cox
      proportional hazards regression model. RESULTS: PET/CT changed the stage group in
      56 of 139 (40%) patients and changed management in 47 of 139 (34%) patients. In
      22 patients, therapy was changed from curative to palliative and in 3 from
      palliative to curative; in 11, treatment modality was changed without a change in
      treatment intent, and in 11 the delivery of therapy or diagnostic procedure was
      changed. Of the 47 patients with management change, imaging results could be
      validated in 31 patients, and PET/CT correctly changed management in 26 (84%) of
      these. Of the remaining 5 patients, CSI stage was also incorrect in 4 and correct
      in 1. Median survival was 23 mo. PET/CT stages I-IIA, IIB-III, and IV had a 5-y
      survival of 40%, 38%, and 6%, respectively. Post-PET/CT stage group and treatment
      intent were both strongly associated with survival (P < 0.001). CONCLUSION:
      PET/CT provides incremental staging information compared with CSI, changes
      management in one third of patients, and has powerful prognostic stratification
      in the primary staging of esophageal cancer.

PMID- 22582048
TI  - Oncologic PET/MRI, part 1: tumors of the brain, head and neck, chest, abdomen,
      and pelvis.
AB  - In oncology, staging forms the basis for prognostic consideration and directly
      influences patient care by determining the therapeutic approach. Cross-sectional
      imaging techniques, especially when combined with PET information, play an
      important role in cancer staging. With the recent introduction of integrated
      whole-body PET/MRI into clinical practice, a novel metabolic-anatomic imaging
      technique is now available. PET/MRI seems to be highly accurate in T-staging of
      tumor entities for which MRI has traditionally been favored, such as squamous
      cell carcinomas of the head and neck. By adding functional MRI to PET, PET/MRI
      may further improve diagnostic accuracy in the differentiation of scar tissue
      from recurrence of tumors such as rectal cancer. This hypothesis will have to be
      assessed in future studies. With regard to N-staging, PET/MRI does not seem to
      provide a considerable benefit as compared with PET/CT but provides similar N
      staging accuracy when applied as a whole-body staging approach. M-staging will
      benefit from MRI accuracy in the brain and the liver. The purpose of this review
      is to summarize the available first experiences with PET/MRI and to outline the
      potential value of PET/MRI in oncologic applications for which data on PET/MRI
      are still lacking.

PMID- 22582049
TI  - Evaluation of response to neoadjuvant chemotherapy for esophageal cancer: PET
      response criteria in solid tumors versus response evaluation criteria in solid
      tumors.
AB  - Recently, PET response criteria in solid tumors (PERCIST) have been proposed as a
      new standardized method to assess chemotherapeutic response metabolically and
      quantitatively. The aim of this study was to evaluate therapeutic response to
      neoadjuvant chemotherapy for locally advanced esophageal cancer, comparing
      PERCIST with the currently widely used response evaluation criteria in solid
      tumors (RECIST). METHODS: Fifty-one patients with locally advanced esophageal
      cancer who received neoadjuvant chemotherapy (5-fluorouracil, adriamycin, and
      cisplatin), followed by surgery were studied. Chemotherapeutic lesion responses
      were evaluated using (18)F-FDG PET and CT according to the RECIST and PERCIST
      methods. The PET/CT scans were obtained before chemotherapy and about 2 wk after
      completion of chemotherapy. Associations were statistically analyzed between
      survival (overall and disease-free survival) and clinicopathologic results
      (histology [well-, moderately, and poorly differentiated squamous cell
      carcinoma], lymphatic invasion, venous invasion, clinical stage, pathologic
      stage, resection level, reduction rate of tumor diameter, reduction rate of tumor
      uptake, chemotherapeutic responses in RECIST and PERCIST, and pathologic
      response). RESULTS: There was a significant difference in response classification
      between RECIST and PERCIST (Wilcoxon signed-rank test, P < 0.0001). Univariate
      analysis showed that lymphatic invasion, venous invasion, resection level,
      pathologic stage, and PERCIST were significant factors associated with disease
      free or overall survival in this study. Although multivariate analysis
      demonstrated that venous invasion (disease-free survival: hazard ratio [HR] =
      4.519, P = 0.002; overall survival: HR = 5.591, P = 0.003) and resection level
      (disease-free survival: HR = 11.078, P = 0.001) were the significant predictors,
      PERCIST was also significant in noninvasive therapy response assessment before
      surgery (disease-free survival: HR = 4.060, P = 0.025; overall survival: HR =
      8.953, P = 0.034). CONCLUSION: RECIST based on the anatomic size reduction rate
      did not demonstrate the correlation between therapeutic responses and prognosis
      in patients with esophageal cancer receiving neoadjuvant chemotherapy. However,
      PERCIST was found to be the strongest independent predictor of outcomes. Given
      the significance of noninvasive radiologic imaging in formulating clinical
      treatment strategies, PERCIST might be considered more suitable for evaluation of
      chemotherapeutic response to esophageal cancer than RECIST.

PMID- 22582050
TI  - Spontaneous body movements in spatial cognition.
AB  - People often perform spontaneous body movements during spatial tasks such as
      giving complex directions or orienting themselves on maps. How are these
      spontaneous gestures related to spatial problem-solving? We measured spontaneous
      movements during a perspective-taking task inspired by map reading. Analyzing the
      motion data to isolate rotation and translation components of motion in specific
      geometric relation to the task, we found out that most participants executed
      spontaneous miniature rotations of the head that were significantly related to
      the main task parameter. These head rotations were as if participants were trying
      to align themselves with the orientation on the map either in the image plane or
      on the ground plane, but with tiny amplitudes, typically below 1% of the actual
      movements. Our results are consistent with a model of sensorimotor prediction
      driving spatial reasoning. The efference copy of planned movements triggers this
      prediction mechanism. The movements themselves may then be mostly inhibited; the
      small spontaneous gestures that we measure are the visible traces of these
      planned but inhibited actions.

PMID- 22582051
TI  - Ammonia inactivation of Ascaris ova in ecological compost by using urine and ash.
AB  - Viable ova of Ascaris lumbricoides, an indicator organism for pathogens, are
      frequently found in feces-derived compost produced from ecological toilets,
      demonstrating that threshold levels of time, temperature, pH, and moisture
      content for pathogen inactivation are not routinely met. Previous studies have
      determined that NH(3) has ovicidal properties for pathogens, including Ascaris
      ova. This research attempted to achieve Ascaris inactivation via NH(3) under
      environmental conditions commonly found in ecological toilets and using materials
      universally available in an ecological sanitation setting, including compost
      (feces and sawdust), urine, and ash. Compost mixed with stored urine and ash
      produced the most rapid inactivation, with significant inactivation observed
      after 2 weeks and with a time to 99% ovum inactivation (T(99)) of 8 weeks.
      Compost mixed with fresh urine and ash achieved a T(99) of 15 weeks, after a 4
      week lag phase. Both matrices had relatively high total-ammonia concentrations
      and pH values of >9.24 (pK(a) of ammonia). In compost mixed with ash only, and in
      compost mixed with fresh urine only, inactivation was observed after an 11-week
      lag phase. These matrices contained NH(3) concentrations of 164 to 173 and 102 to
      277 mg/liter, respectively, when inactivation occurred, which was below the
      previously hypothesized threshold for inactivation (280 mg/liter), suggesting
      that a lower threshold NH(3) concentration may be possible with a longer contact
      time. Other significant results include the hydrolysis of urea to ammonia between
      pH values of 10.4 and 11.6, above the literature threshold pH of 10.

PMID- 22582052
TI  - Novel phytases from Bifidobacterium pseudocatenulatum ATCC 27919 and
      Bifidobacterium longum subsp. infantis ATCC 15697.
AB  - Two  novel phytases have been characterized from Bifidobacterium
      pseudocatenulatum and Bifidobacterium longum subsp. infantis. The enzymes belong
      to a new subclass within the histidine acid phytases, are highly specific for the
      hydrolysis of phytate, and render myo-inositol triphosphate as the final
      hydrolysis product. They represent the first phytases characterized from this
      group of probiotic microorganisms, opening the possibilities for their use in the
      processing of high-phytate-content foods.

PMID- 22582053
TI  - Biochemical characterization of a novel haloalkane dehalogenase from a cold
      adapted bacterium.
AB  - A haloalkane dehalogenase, DpcA, from Psychrobacter cryohalolentis K5,
      representing a novel psychrophilic member of the haloalkane dehalogenase family,
      was identified and biochemically characterized. DpcA exhibited a unique
      temperature profile with exceptionally high activities at low temperatures. The
      psychrophilic properties of DpcA make this enzyme promising for various
      environmental applications.

PMID- 22582055
TI  - Production of the antimicrobial secondary metabolite indigoidine contributes to
      competitive surface colonization by the marine roseobacter Phaeobacter sp. strain
      Y4I.
AB  - Members of the Roseobacter lineage of marine bacteria are prolific surface
      colonizers in marine coastal environments, and antimicrobial secondary metabolite
      production has been hypothesized to provide a competitive advantage to colonizing
      roseobacters. Here, we report that the roseobacter Phaeobacter sp. strain Y4I
      produces the blue pigment indigoidine via a nonribosomal peptide synthase (NRPS)
      based biosynthetic pathway encoded by a novel series of genetically linked genes:
      igiBCDFE. A Tn5-based random mutagenesis library of Y4I showed a perfect
      correlation between indigoidine production by the Phaeobacter strain and
      inhibition of Vibrio fischeri on agar plates, revealing a previously unrecognized
      bioactivity of this molecule. In addition, igiD null mutants (igiD encoding the
      indigoidine NRPS) were more resistant to hydrogen peroxide, less motile, and
      faster to colonize an artificial surface than the wild-type strain. Collectively,
      these data provide evidence for pleiotropic effects of indigoidine production in
      this strain. Gene expression assays support phenotypic observations and
      demonstrate that igiD gene expression is upregulated during growth on surfaces.
      Furthermore, competitive cocultures of V. fischeri and Y4I show that the
      production of indigoidine by Y4I significantly inhibits colonization of V.
      fischeri on surfaces. This study is the first to characterize a secondary
      metabolite produced by an NRPS in roseobacters.

PMID- 22582056
TI  - Phylomark, a tool to identify conserved phylogenetic markers from whole-genome
      alignments.
AB  - The sequencing and analysis of multiple housekeeping genes has been routinely
      used to phylogenetically compare closely related bacterial isolates. Recent
      studies using whole-genome alignment (WGA) and phylogenetics from >100
      Escherichia coli genomes has demonstrated that tree topologies from WGA and
      multilocus sequence typing (MLST) markers differ significantly. A
      nonrepresentative phylogeny can lead to incorrect conclusions regarding important
      evolutionary relationships. In this study, the Phylomark algorithm was developed
      to identify a minimal number of useful phylogenetic markers that recapitulate the
      WGA phylogeny. To test the algorithm, we used a set of diverse draft and complete
      E. coli genomes. The algorithm identified more than 100,000 potential markers of
      different fragment lengths (500 to 900 nucleotides). Three molecular markers were
      ultimately chosen to determine the phylogeny based on a low Robinson-Foulds (RF)
      distance compared to the WGA phylogeny. A phylogenetic analysis demonstrated that
      a more representative phylogeny was inferred for a concatenation of these markers
      compared to all other MLST schemes for E. coli. As a functional test of the
      algorithm, the three markers (genomic guided E. coli markers, or GIG-EM) were
      amplified and sequenced from a set of environmental E. coli strains (ECOR
      collection) and informatically extracted from a set of 78 diarrheagenic E. coli
      strains (DECA collection). In the instances of the 40-genome test set and the
      DECA collection, the GIG-EM system outperformed other E. coli MLST systems in
      terms of recapitulating the WGA phylogeny. This algorithm can be employed to
      determine the minimal marker set for any organism that has sufficient genome
      sequencing.

PMID- 22582054
TI  - Syntrophic oxidation of propionate in rice field soil at 15 and 30 degrees C
      under methanogenic conditions.
AB  - Propionate is one of the major intermediary products in the anaerobic
      decomposition of organic matter in wetlands and paddy fields. Under methanogenic
      conditions, propionate is decomposed through syntrophic interaction between
      proton-reducing and propionate-oxidizing bacteria and H(2)-consuming methanogens.
      Temperature is an important environmental regulator; yet its effect on syntrophic
      propionate oxidation has been poorly understood. In the present study, we
      investigated the syntrophic oxidation of propionate in a rice field soil at 15
      degrees C and 30 degrees C. [U-(13)C]propionate (99 atom%) was applied to anoxic
      soil slurries, and the bacteria and archaea assimilating (13)C were traced by DNA
      based stable isotope probing. Syntrophobacter spp., Pelotomaculum spp., and
      Smithella spp. were found significantly incorporating (13)C into their nucleic
      acids after [(13)C]propionate incubation at 30 degrees C. The activity of
      Smithella spp. increased in the later stage, and concurrently that of
      Syntrophomonas spp. increased. Aceticlastic Methanosaetaceae and hydrogenotrophic
      Methanomicrobiales and Methanocellales acted as methanogenic partners at 30
      degrees C. Syntrophic oxidation of propionate also occurred actively at 15
      degrees C. Syntrophobacter spp. were significantly labeled with (13)C, whereas
      Pelotomaculum spp. were less active at this temperature. In addition,
      Methanomicrobiales, Methanocellales, and Methanosarcinaceae dominated the
      methanogenic community, while Methanosaetaceae decreased. Collectively,
      temperature markedly influenced the activity and community structure of
      syntrophic guilds degrading propionate in the rice field soil. Interestingly,
      Geobacter spp. and some other anaerobic organisms like Rhodocyclaceae,
      Acidobacteria, Actinobacteria, and Thermomicrobia probably also assimilated
      propionate-derived (13)C. The mechanisms for the involvement of these organisms
      remain unclear.

PMID- 22582057
TI  - Natural transformation of Gallibacterium anatis.
AB  - Gallibacterium anatis is a pathogen of poultry. Very little is known about its
      genetics and pathogenesis. To enable the study of gene function in G. anatis, we
      have established methods for transformation and targeted mutagenesis. The genus
      Gallibacterium belongs to the Pasteurellaceae, a group with several naturally
      transformable members, including Haemophilus influenzae. Bioinformatics analysis
      identified G. anatis homologs of the H. influenzae competence genes, and natural
      competence was induced in G. anatis by the procedure established for H.
      influenzae: transfer from rich medium to the starvation medium M-IV. This
      procedure gave reproducibly high transformation frequencies with G. anatis
      chromosomal DNA and with linearized plasmid DNA carrying G. anatis sequences.
      Both DNA types integrated into the G. anatis chromosome by homologous
      recombination. Targeted mutagenesis gave transformation frequencies of >2 * 10(
      4) transformants CFU(-1). Transformation was also efficient with circular plasmid
      containing no G. anatis DNA; this resulted in the establishment of a self
      replicating plasmid. Nine diverse G. anatis strains were found to be naturally
      transformable by this procedure, suggesting that natural competence is common and
      the M-IV transformation procedure widely applicable for this species. The G.
      anatis genome is only slightly enriched for the uptake signal sequences
      identified in other pasteurellaceaen genomes, but G. anatis did preferentially
      take up its own DNA over that of Escherichia coli. Transformation by
      electroporation was not effective for chromosomal integration but could be used
      to introduce self-replicating plasmids. The findings described here provide
      important tools for the genetic manipulation of G. anatis.

PMID- 22582058
TI  - Proteomic phenotyping of Novosphingobium nitrogenifigens reveals a robust
      capacity for simultaneous nitrogen fixation, polyhydroxyalkanoate production, and
      resistance to reactive oxygen species.
AB  - Novosphingobium nitrogenifigens Y88(T) (Y88) is a free-living, diazotrophic
      Alphaproteobacterium, capable of producing 80% of its biomass as the biopolymer
      polyhydroxybutyrate (PHB). We explored the potential utility of this species as a
      polyhydroxybutyrate production strain, correlating the effects of glucose,
      nitrogen availability, dissolved oxygen concentration, and extracellular pH with
      polyhydroxybutyrate production and changes in the Y88 proteomic profile. Using
      two-dimensional differential in-gel electrophoresis and tandem mass spectrometry,
      we identified 217 unique proteins from six growth conditions. We observed
      reproducible, characteristic proteomic signatures for each of the physiological
      states we examined. We identified proteins that changed in abundance in
      correlation with either nitrogen fixation, dissolved oxygen concentration, or
      acidification of the growth medium.  The proteins that correlated with nitrogen
      fixation were identified either as known nitrogen fixation proteins or as novel
      proteins that we predict play roles in aspects of nitrogen fixation based on
      their proteomic profiles. In contrast, the proteins involved in central carbon
      and polyhydroxybutyrate metabolism were constitutively abundant, consistent with
      the constitutive polyhydroxybutyrate production that we observed in this species.
      Three proteins with roles in detoxification of reactive oxygen species were
      identified in this obligate aerobe. The most abundant protein in all experiments
      was a polyhydroxyalkanoate granule-associated protein, phasin. The full-length
      isoform of this protein has a long, intrinsically disordered Ala/Pro/Lys-rich N
      terminal segment, a feature that appears to be unique to sphingomonad phasins.
      The data suggest that Y88 has potential as a PHB production strain due to its
      aerobic tolerance and metabolic orientation toward polyhydroxybutyrate
      accumulation, even in low-nitrogen growth medium.

PMID- 22582059
TI  - Identification of a novel dihydrodaidzein racemase essential for biosynthesis of
      equol from daidzein in Lactococcus sp. strain 20-92.
AB  - Equol is metabolized from daidzein, a soy isoflavone, by the gut microflora. In
      this study, we identified a novel dihydrodaidzein racemase (L-DDRC) that is
      involved in equol biosynthesis in a lactic acid bacterium, Lactococcus sp. strain
      20-92, and confirmed that histidine-tagged recombinant L-DDRC (L-DDRC-His) was
      able to convert both the (R)- and (S)-enantiomers of dihydrodaidzein to the
      racemate. Moreover, we showed that recombinant L-DDRC-His was essential for in
      vitro equol production from daidzein by a recombinant enzyme mixture and that
      efficient in vitro equol production from daidzein was possible using at least
      four enzymes, including L-DDRC. We also proposed a model of the metabolic pathway
      from daidzein to equol in Lactococcus strain 20-92.

PMID- 22582060
TI  - Associations of yeasts with spotted-wing Drosophila (Drosophila suzukii; Diptera:
      Drosophilidae) in cherries and raspberries.
AB  - A rich history of investigation documents various Drosophila-yeast mutualisms,
      suggesting that Drosophila suzukii similarly has an association with a specific
      yeast species or community. To discover candidate yeast species, yeasts were
      isolated from larval frass, adult midguts, and fruit hosts of D. suzukii.
      Terminal restriction fragment length polymorphism (TRFLP) technology and decimal
      dilution plating were used to identify and determine the relative abundance of
      yeast species present in fruit juice samples that were either infested with D.
      suzukii or not infested. Yeasts were less abundant in uninfested than infested
      samples. A total of 126 independent yeast isolates were cultivated from frass,
      midguts, and fruit hosts of D. suzukii, representing 28 species of yeasts, with
      Hanseniaspora uvarum predominating. This suggests an association between D.
      suzukii and H. uvarum that could be utilized for pest management of the highly
      pestiferous D. suzukii.

PMID- 22582061
TI  - Development of a double-crossover markerless gene deletion system in
      Bifidobacterium longum: functional analysis of the alpha-galactosidase gene for
      raffinose assimilation.
AB  - Functional analysis of Bifidobacterium genes is essential for understanding host
      Bifidobacterium interactions with beneficial effects on human health; however,
      the lack of an effective targeted gene inactivation system in bifidobacteria has
      prevented the development of functional genomics in this bacterium. Here, we
      report the development of a markerless gene deletion system involving a double
      crossover in Bifidobacterium longum. Incompatible plasmid vectors were used to
      facilitate a second crossover step. The conditional replication vector pBS423
      DeltarepA, which lacks the plasmid replication gene repA, was integrated into the
      target gene by a first crossover event. Subsequently, the replicative plasmid
      pTBR101-CM, which harbors repA, was introduced into this integrant to facilitate
      the second crossover step and subsequent elimination of the excised conditional
      replication vector from the cells by plasmid incompatibility. The proposed system
      was confirmed to work as expected in B. longum 105-A using the chromosomal full
      length beta-galactosidase gene as a target. Markerless gene deletion was tested
      using the aga gene, which encodes alpha-galactosidase, whose substrates include
      raffinose. Almost all the pTBR101-CM-transformed strains became double-crossover
      recombinants after subculture, and 4 out of the 270 double-crossover recombinants
      had lost the ability to assimilate raffinose. Genotype analysis of these strains
      revealed markerless gene deletion of aga. Carbohydrate assimilation analysis and
      alpha-galactosidase activity measurement were conducted using both the
      representative mutant and a plasmid-based aga-complemented strain. These
      functional analyses revealed that aga is the only gene encoding a functional
      alpha-galactosidase enzyme in B. longum 105-A.

PMID- 22582062
TI  - Sensitive quantification of Clostridium difficile cells by reverse transcription
      quantitative PCR targeting rRNA molecules.
AB  - We established a sensitive and accurate quantification system for Clostridium
      difficile in human intestines, based on rRNA-targeted reverse transcription
      quantitative PCR (RT-qPCR). We newly developed a species-specific primer set for
      C. difficile targeting 23S rRNA gene sequences. Both the vegetative cells and the
      spores of C. difficile in human feces were quantified by RT-qPCR, with a lower
      detection limit of 10(2.4) cells/g of feces. In an analysis of the feces of
      residents (n = 83; age, 85 +/- 8 years) and staff (n = 19; age, 36 +/- 10 years)
      at a care facility for the elderly, C. difficile was detected by RT-qPCR in 43%
      of the residents (average count, log(10) 4.0 +/- 2.0 cells/g of feces) and 16% of
      the staff (average count, log(10) 2.2 +/- 0.1 cells/g of feces); these rates were
      far higher than those detected by qPCR (residents, 19%; staff, 0%) or selective
      cultivation (residents, 18%; staff, 5%). Another analysis of healthy adults (n =
      63; age, 41 +/- 11 years) also revealed the significant carriage rate of C.
      difficile in the intestines (detection rate, 13%; average count, log(10) 4.9 +/-
      1.2 cells/g of feces). From these results, it was suggested that rRNA-targeted RT
      qPCR should be an effective tool for analyzing population levels of C. difficile
      in the human intestine.

PMID- 22582063
TI  - Galacturonic acid inhibits the growth of Saccharomyces cerevisiae on galactose,
      xylose, and arabinose.
AB  - The efficient fermentation of mixed substrates is essential for the microbial
      conversion of second-generation feedstocks, including pectin-rich waste streams
      such as citrus peel and sugar beet pulp. Galacturonic acid is a major constituent
      of hydrolysates of these pectin-rich materials. The yeast Saccharomyces
      cerevisiae, the main producer of bioethanol, cannot use this sugar acid. The
      impact of galacturonic acid on alcoholic fermentation by S. cerevisiae was
      investigated with anaerobic batch cultures grown on mixtures of glucose and
      galactose at various galacturonic acid concentrations and on a mixture of
      glucose, xylose, and arabinose. In cultures grown at pH 5.0, which is well above
      the pK(a) value of galacturonic acid (3.51), the addition of 10 g . liter(-1)
      galacturonic acid did not affect galactose fermentation kinetics and growth. In
      cultures grown at pH 3.5, the addition of 10 g . liter(-1) galacturonic acid did
      not significantly affect glucose consumption. However, at this lower pH,
      galacturonic acid completely inhibited growth on galactose and reduced galactose
      consumption rates by 87%. Additionally, it was shown that galacturonic acid
      strongly inhibits the fermentation of xylose and arabinose by the engineered
      pentose-fermenting S. cerevisiae strain IMS0010. The data indicate that
      inhibition occurs when nondissociated galacturonic acid is present
      extracellularly and corroborate the hypothesis that a combination of a decreased
      substrate uptake rate due to competitive inhibition on Gal2p, an increased energy
      requirement to maintain cellular homeostasis, and/or an accumulation of
      galacturonic acid 1-phosphate contributes to the inhibition. The role of
      galacturonic acid as an inhibitor of sugar fermentation should be considered in
      the design of yeast fermentation processes based on pectin-rich feedstocks.

PMID- 22582064
TI  - Fluorescence-based reporter for gauging cyclic di-GMP levels in Pseudomonas
      aeruginosa.
AB  - The increased tolerance toward the host immune system and antibiotics displayed
      by biofilm-forming Pseudomonas aeruginosa and other bacteria in chronic
      infections such as cystic fibrosis bronchopneumonia is of major concern.
      Targeting of biofilm formation is believed to be a key aspect in the development
      of novel antipathogenic drugs that can augment the effect of classic antibiotics
      by decreasing antimicrobial tolerance. The second messenger cyclic di-GMP is a
      positive regulator of biofilm formation, and cyclic di-GMP signaling is now
      regarded as a potential target for the development of antipathogenic compounds.
      Here we describe the development of fluorescent monitors that can gauge the
      cellular level of cyclic di-GMP in P. aeruginosa. We have created cyclic di-GMP
      level reporters by transcriptionally fusing the cyclic di-GMP-responsive cdrA
      promoter to genes encoding green fluorescent protein. We show that the reporter
      constructs give a fluorescent readout of the intracellular level of cyclic di-GMP
      in P. aeruginosa strains with different levels of cyclic di-GMP. Furthermore, we
      show that the reporters are able to detect increased turnover of cyclic di-GMP
      mediated by treatment of P. aeruginosa with the phosphodiesterase inducer nitric
      oxide. Considering that biofilm formation is a necessity for the subsequent
      development of a chronic infection and therefore a pathogenicity trait, the
      reporters display a significant potential for use in the identification of novel
      antipathogenic compounds targeting cyclic di-GMP signaling, as well as for use in
      research aiming at understanding the biofilm biology of P. aeruginosa.

PMID- 22582065
TI  - Improvement of FK506 production in Streptomyces tsukubaensis by genetic
      enhancement of the supply of unusual polyketide extender units via utilization of
      two distinct site-specific recombination systems.
AB  - FK506 is a potent immunosuppressant that has a wide range of clinical
      applications. Its 23-member macrocyclic scaffold, mainly with a polyketide
      origin, features two methoxy groups at C-13 and C-15 and one allyl side chain at
      C-21, due to the region-specific incorporation of two unusual extender units
      derived from methoxymalonyl-acyl carrier protein (ACP) and allylmalonyl-coenzyme
      A (CoA), respectively. Whether their intracellular formations can be a bottleneck
      for FK506 production remains elusive. In this study, we report the improvement of
      FK506 yield in the producing strain Streptomyces tsukubaensis by the duplication
      of two sets of pathway-specific genes individually encoding the biosyntheses of
      these two extender units, thereby providing a promising approach to generate high
      FK506-producing strains via genetic manipulation. Taking advantage of the fact
      that S. tsukubaensis is amenable to two actinophage (PhiC31 and VWB) integrase
      mediated recombination systems, we genetically enhanced the biosyntheses of
      methoxymalonyl-ACP and allylmalonyl-CoA, as indicated by transcriptional
      analysis. Together with the optimization of glucose supplementation, the maximal
      FK506 titer eventually increased by approximately 150% in comparison with that of
      the original strain. The strategy of engineering the biosynthesis of unusual
      extender units described here may be applicable to improving the production of
      other polyketide or nonribosomal peptide natural products that contain pathway
      specific building blocks.

PMID- 22582066
TI  - Microbial degradation of 2,4-dichlorophenoxyacetic acid on the Greenland ice
      sheet.
AB  - The Greenland ice sheet (GrIS) receives organic carbon (OC) of anthropogenic
      origin, including pesticides, from the atmosphere and/or local sources, and the
      fate of these compounds in the ice is currently unknown. The ability of
      supraglacial heterotrophic microbes to mineralize different types of OC is likely
      a significant factor determining the fate of anthropogenic OC on the ice sheet.
      Here we determine the potential of the microbial community from the surface of
      the GrIS to mineralize the widely used herbicide 2,4-dichlorophenoxyacetic acid
      (2,4-D). Surface ice cores were collected and incubated for up to 529 days in
      microcosms simulating in situ conditions. Mineralization of side chain- and ring
      labeled [(14)C]2,4-D was measured in the samples, and quantitative PCR targeting
      the tfdA genes in total DNA extracted from the ice after the experiment was
      performed. We show that the supraglacial microbial community on the GrIS contains
      microbes that are capable of degrading 2,4-D and that they are likely present in
      very low numbers. They can mineralize 2,4-D at a rate of up to 1 nmol per m(2)
      per day, equivalent to ~26 ng C m(-2) day(-1). Thus, the GrIS should not be
      considered a mere reservoir of all atmospheric contaminants, as it is likely that
      some deposited compounds will be removed from the system via biodegradation
      processes before their potential release due to the accelerated melting of the
      ice sheet.

PMID- 22582067
TI  - Involvement of PatE, a prophage-encoded AraC-like regulator, in the
      transcriptional activation of acid resistance pathways of enterohemorrhagic
      Escherichia coli strain EDL933.
AB  - Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a lethal human intestinal
      pathogen that causes hemorrhagic colitis and the hemolytic-uremic syndrome. EHEC
      is transmitted by the fecal-oral route and has a lower infectious dose than most
      other enteric bacterial pathogens in that fewer than 100 CFU are able to cause
      disease. This low infectious dose has been attributed to the ability of EHEC to
      survive in the acidic environment of the human stomach. In silico analysis of the
      genome of EHEC O157:H7 strain EDL933 revealed a gene, patE, for a putative AraC
      like regulatory protein within the prophage island, CP-933H. Transcriptional
      analysis in E. coli showed that the expression of patE is induced during
      stationary phase. Data from microarray assays demonstrated that PatE activates
      the transcription of genes encoding proteins of acid resistance pathways. In
      addition, PatE downregulated the expression of a number of genes encoding heat
      shock proteins and the type III secretion pathway of EDL933. Transcriptional
      analysis and electrophoretic mobility shift assays suggested that PatE also
      activates the transcription of the gene for the acid stress chaperone hdeA by
      binding to its promoter region. Finally, assays of acid tolerance showed that
      increasing the expression of PatE in EHEC greatly enhanced the ability of the
      bacteria to survive in different acidic environments. Together, these findings
      indicate that EHEC strain EDL933 carries a prophage-encoded regulatory system
      that contributes to acid resistance.

PMID- 22582068
TI  - Cold atmospheric air plasma sterilization against spores and other microorganisms
      of clinical interest.
AB  - Physical cold atmospheric surface microdischarge (SMD) plasma operating in
      ambient air has promising properties for the sterilization of sensitive medical
      devices where conventional methods are not applicable. Furthermore, SMD plasma
      could revolutionize the field of disinfection at health care facilities. The
      antimicrobial effects on Gram-negative and Gram-positive bacteria of clinical
      relevance, as well as the fungus Candida albicans, were tested. Thirty seconds of
      plasma treatment led to a 4 to 6 log(10) CFU reduction on agar plates. C.
      albicans was the hardest to inactivate. The sterilizing effect on standard
      bioindicators (bacterial endospores) was evaluated on dry test specimens that
      were wrapped in Tyvek coupons. The experimental D(23)( degrees )(C) values for
      Bacillus subtilis, Bacillus pumilus, Bacillus atrophaeus, and Geobacillus
      stearothermophilus were determined as 0.3 min, 0.5 min, 0.6 min, and 0.9 min,
      respectively. These decimal reduction times (D values) are distinctly lower than
      D values obtained with other reference methods. Importantly, the high
      inactivation rate was independent of the material of the test specimen. Possible
      inactivation mechanisms for relevant microorganisms are briefly discussed,
      emphasizing the important role of neutral reactive plasma species and pointing to
      recent diagnostic methods that will contribute to a better understanding of the
      strong biocidal effect of SMD air plasma.

PMID- 22582069
TI  - A straightforward DOPE (double labeling of oligonucleotide probes)-FISH
      (fluorescence in situ hybridization) method for simultaneous multicolor detection
      of six microbial populations.
AB  - Fluorescence in situ hybridization (FISH) with rRNA-targeted oligonucleotide
      probes is an essential tool for the cultivation-independent identification of
      microbes within environmental and clinical samples. However, one of the major
      constraints of conventional FISH is the very limited number of different target
      organisms that can be detected simultaneously with standard epifluorescence or
      confocal laser scanning microscopy. Recently, this limitation has been overcome
      via an elegant approach termed combinatorial labeling and spectral imaging FISH
      (CLASI-FISH) (23). This technique, however, suffers compared to conventional FISH
      from an inherent loss in sensitivity and potential probe binding biases caused by
      the competition of two differentially labeled oligonucleotide probes for the same
      target site. Here we demonstrate that the application of multicolored, double
      labeled oligonucleotide probes enables the simultaneous detection of up to six
      microbial target populations in a straightforward and robust manner with higher
      sensitivity and less bias. Thus, this newly developed technique should be an
      attractive option for all researchers interested in applying conventional FISH
      methods for the study of microbial communities.

PMID- 22582070
TI  - Detection of imported wild polioviruses and of vaccine-derived polioviruses by
      environmental surveillance in Egypt.
AB  - Systematic environmental surveillance for poliovirus circulation has been
      conducted in Egypt since 2000. The surveillance has revealed three independent
      importations of wild-type poliovirus. In addition, several vaccine-derived
      polioviruses have been detected in various locations in Egypt. In addition to
      acute flaccid paralysis (AFP) surveillance, environmental surveillance can be
      used to monitor the wild poliovirus and vaccine-derived poliovirus circulation in
      populations in support of polio eradication initiatives.

PMID- 22582071
TI  - Epoxy Coenzyme A Thioester pathways for degradation of aromatic compounds.
AB  - Aromatic compounds (biogenic and anthropogenic) are abundant in the biosphere.
      Some of them are well-known environmental pollutants. Although the aromatic
      nucleus is relatively recalcitrant, microorganisms have developed various
      catabolic routes that enable complete biodegradation of aromatic compounds. The
      adopted degradation pathways depend on the availability of oxygen. Under oxic
      conditions, microorganisms utilize oxygen as a cosubstrate to activate and cleave
      the aromatic ring. In contrast, under anoxic conditions, the aromatic compounds
      are transformed to coenzyme A (CoA) thioesters followed by energy-consuming
      reduction of the ring. Eventually, the dearomatized ring is opened via a
      hydrolytic mechanism. Recently, novel catabolic pathways for the aerobic
      degradation of aromatic compounds were elucidated that differ significantly from
      the established catabolic routes. The new pathways were investigated in detail
      for the aerobic bacterial degradation of benzoate and phenylacetate. In both
      cases, the pathway is initiated by transforming the substrate to a CoA thioester
      and all the intermediates are bound by CoA. The subsequent reactions involve
      epoxidation of the aromatic ring followed by hydrolytic ring cleavage. Here we
      discuss the novel pathways, with a particular focus on their unique features and
      occurrence as well as ecological significance.

PMID- 22582072
TI  - Detection of Coxiella burnetii DNA in inhalable airborne dust samples from goat
      farms after mandatory culling.
AB  - Coxiella burnetii is thought to infect humans primarily via airborne
      transmission. However, air measurements of C. burnetii are sparse. We detected C.
      burnetii DNA in inhalable and PM10 (particulate matter with an aerodynamic size
      of 10 MUm or less) dust samples collected at three affected goat farms,
      demonstrating that low levels of C. burnetii DNA are present in inhalable size
      fractions.

PMID- 22582073
TI  - Diversity of gene cassette promoters in class 1 integrons from wastewater
      environments.
AB  - The diversity of gene cassette promoters in class 1 integrons was investigated in
      47 strains isolated from wastewaters. The weak PcW and PcH1 variants
      predominated, suggesting that, similar to clinical environments, high rates of
      gene cassette recombination, rather than high expression of gene cassettes, have
      been preferentially selected in wastewaters.

PMID- 22582074
TI  - Quantitative estimation of the viability of Toxoplasma gondii oocysts in soil.
AB  - Toxoplasma gondii oocysts spread in the environment are an important source of
      toxoplasmosis for humans and animal species. Although the life expectancy of
      oocysts has been studied through the infectivity of inoculated soil samples, the
      survival dynamics of oocysts in the environment are poorly documented. The aim of
      this study was to quantify oocyst viability in soil over time under two rain
      conditions. Oocysts were placed in 54 sentinel chambers containing soil and 18
      sealed water tubes, all settled in two containers filled with soil. Containers
      were watered to simulate rain levels of arid and wet climates and kept at stable
      temperature for 21.5 months. At nine sampling dates during this period, we
      sampled six chambers and two water tubes. Three methods were used to measure
      oocyst viability: microscopic counting, quantitative PCR (qPCR), and mouse
      inoculation. In parallel, oocysts were kept refrigerated during the same period
      to analyze their detectability over time. Microscopic counting, qPCR, and mouse
      inoculation all showed decreasing values over time and highly significant
      differences between the decreases under dry and damp conditions. The proportion
      of oocysts surviving after 100 days was estimated to be 7.4% (95% confidence
      interval [95% CI] = 5.1, 10.8) under dry conditions and 43.7% (5% CI = 35.6,
      53.5) under damp conditions. The detectability of oocysts by qPCR over time
      decreased by 0.5 cycle threshold per 100 days. Finally, a strong correlation
      between qPCR results and the dose infecting 50% of mice was found; thus, qPCR
      results may be used as an estimate of the infectivity of soil samples.

PMID- 22582075
TI  - Enhanced tolerance to naphthalene and enhanced rhizoremediation performance for
      Pseudomonas putida KT2440 via the NAH7 catabolic plasmid.
AB  - In this work, we explore the potential use of the Pseudomonas putida KT2440
      strain for bioremediation of naphthalene-polluted soils. Pseudomonas putida
      strain KT2440 thrives in naphthalene-saturated medium, establishing a complex
      response that activates genes coding for extrusion pumps and cellular damage
      repair enzymes, as well as genes involved in the oxidative stress response. The
      transfer of the NAH7 plasmid enables naphthalene degradation by P. putida KT2440
      while alleviating the cellular stress brought about by this toxic compound,
      without affecting key functions necessary for survival and colonization of the
      rhizosphere. Pseudomonas putida KT2440(NAH7) efficiently expresses the Nah
      catabolic pathway in vitro and in situ, leading to the complete mineralization of
      [(14)C]naphthalene, measured as the evolution of (14)CO(2), while the rate of
      mineralization was at least 2-fold higher in the rhizosphere than in bulk soil.

PMID- 22582076
TI  - Accessing the inaccessible: molecular tools for bifidobacteria.
AB  - Bifidobacteria are an important group of the human intestinal microbiota that
      have been shown to exert a number of beneficial probiotic effects on the health
      status of their host. Due to these effects, bifidobacteria have attracted strong
      interest in health care and food industries for probiotic applications and
      several species are listed as so-called "generally recognized as safe" (GRAS)
      microorganisms. Moreover, recent studies have pointed out their potential as an
      alternative or supplementary strategy in tumor therapy or as live vaccines. In
      order to study the mechanisms by which these organisms exert their beneficial
      effects and to generate recombinant strains that can be used as drug delivery
      vectors or live vaccines, appropriate molecular tools are indispensable. This
      review provides an overview of the currently available methods and tools to
      generate recombinant strains of bifidobacteria. The currently used protocols for
      transformation of bifidobacteria, as well as replicons, selection markers, and
      determinants of expression, will be summarized. We will further discuss
      promoters, terminators, and localization signals that have been used for
      successful generation of expression vectors.

PMID- 22582077
TI  - Lactobacillus reuteri protects epidermal keratinocytes from Staphylococcus aureus
      induced cell death by competitive exclusion.
AB  - Recent studies have suggested that the topical application of probiotic bacteria
      can improve skin health or combat disease. We have utilized a primary human
      keratinocyte culture model to investigate whether probiotic bacteria can inhibit
      Staphylococcus aureus infection. Evaluation of the candidate probiotics
      Lactobacillus reuteri ATCC 55730, Lactobacillus rhamnosus AC413, and
      Lactobacillus salivarius UCC118 demonstrated that both L. reuteri and L.
      rhamnosus, but not L. salivarius, reduced S. aureus-induced keratinocyte cell
      death in both undifferentiated and differentiated keratinocytes. Keratinocyte
      survival was significantly higher if the probiotic was applied prior to (P <
      0.01) or simultaneously with (P < 0.01) infection with S. aureus but not when
      added after infection had commenced (P > 0.05). The protective effect of L.
      reuteri was not dependent on the elaboration of inhibitory substances such as
      lactic acid. L. reuteri inhibited adherence of S. aureus to keratinocytes by
      competitive exclusion (P = 0.026). L. salivarius UCC118, however, did not inhibit
      S. aureus from adhering to keratinocytes (P > 0.05) and did not protect
      keratinocyte viability. S. aureus utilizes the alpha5beta1 integrin to adhere to
      keratinocytes, and blocking of this integrin resulted in a protective effect
      similar to that observed with probiotics (P = 0.03). This suggests that the
      protective mechanism for L. reuteri-mediated protection of keratinocytes was by
      competitive exclusion of the pathogen from its binding sites on the cells. Our
      results suggest that use of a topical probiotic prophylactically could inhibit
      the colonization of skin by S. aureus and thus aid in the prevention of
      infection.

PMID- 22582079
TI  - Transgenerational epigenetic inheritance in animals.

PMID- 22582078
TI  - TCR Nanoclusters as the Framework for Transmission of Conformational Changes and
      Cooperativity.
AB  - Increasing evidence favors the notion that, before triggering, the T cell antigen
      receptor (TCR) forms nanometer-scale oligomers that are called nanoclusters. The
      organization of the TCR in pre-existing oligomers cannot be ignored when
      analyzing the properties of ligand (pMHC) recognition and signal transduction. As
      with other membrane receptors, the existence of TCR oligomers points out to
      cooperativity phenomena. We review the data in support of conformational changes
      in the TCR as the basic principle to transduce the activation signal to the
      cytoplasm and the incipient data suggesting cooperativity within nanoclusters.

PMID- 22582081
TI  - Dual color multiplex TTF-1 + Napsin A and p63 + CK5 immunostaining for
      subcategorizing of poorly differentiated pulmonary non-small carcinomas into
      adenocarcinoma and squamous cell carcinoma in fine needle aspiration specimens.
AB  - BACKGROUND: The distinction of lung adenocarcinoma (ADC) from squamous cell
      carcinoma (SCC) has important therapeutic implications. Napsin A is a recently
      developed marker, which has shown high specificity for lung tissue in the
      surgical pathology specimens. In this study, we have evaluated whether the use of
      a panel of novel multiplex cocktails of TTF-1 + Napsin A and p63 + CK5 for dual
      color immunostaining will improve the diagnostic accuracy of lung adenocarcinoma
      and squamous cell carcinoma in fine needle aspiration (FNA) specimens, usually
      with relatively scant microfragments of diagnostic material. MATERIALS AND
      METHODS: Formalin-fixed, paraffin-embedded, adequately cellular FNA cell blocks
      with a confirmed diagnosis of either ADC (n = 22), SCC (n = 20) or poorly
      differentiated carcinoma (PDC; n = 7), from a total of 49 consecutive cases, were
      studied. All these cases had subsequently confirmed diagnosis in biopsies or
      resection specimens. The sections were immunostained with two color methods of
      TTF-1 + Napsin A and p63 + CK5 multiplex cocktails. The presence of one or more
      unequivocal individual tumor cells with convincing brown nuclear TTF-1 and red
      cytoplasmic Napsin A staining, and cells with brown nuclear p63 and membranous /
      cytoplasmic CK5 staining were interpreted as 'positive'. RESULTS: All 20 FNA cell
      blocks from SCC cases were positive for dual stain p63 + CK5 and negative for
      dual stain TTF-1 + Napsin A. The sensitivity and specificity of the dual
      immunoexpressions of p63 + CK5 for SCC of lung FNAs were both 100%. All 22 ADC
      cases were positive with dual stain of TTF-1 + Napsin A and negative for dual
      stain of p63 + CK5. On follow-up of the surgical pathology specimens, 22 cases
      were confirmed as ADC. The sensitivity of the dual immunoexpression of TTF-1 +
      Napsin A for ADC of lung FNAs was 100% and the specificity was also 100%. Of the
      seven PDC cases, five cases that were positive for dual stain p63 + CK5 and
      negative for dual stain TTF-1 + Napsin A could be categorized as SCC. Two of the
      seven (2 / 7) PDC cases were positive for dual stain TTF-1 + Napsin A and
      negative for dual stain p63 + CK5, consistent with ADC. CONCLUSIONS: Simultaneous
      coordinate or individual immunostaining for Napsin A / TTF-1 in ADC and p63 / CK5
      in SCC demonstrated high sensitivity and specificity. The panel with multiplex
      Napsin A / TTF-1 and p63 / CK5 dual color immunostains could specifically
      subcategorize PDC into ADC and SCC in lung FNA specimens. Multiplex dual color
      Napsin A / TTF-1 and p63 / CK5 immunostaining is especially recommended for
      evaluation of FNA specimens with relatively scant cellularity.

PMID- 22582082
TI  - Force field evolution during human blood platelet activation.
AB  - Contraction at the cellular level is vital for living organisms. The most
      prominent type of contractile cells are heart muscle cells, a less-well-known
      example is blood platelets. Blood platelets activate and interlink at injured
      blood vessel sites, finally contracting to form a compact blood clot. They are
      ideal model cells to study the mechanisms of cellular contraction, as they are
      simple, having no nucleus, and their activation can be triggered and synchronized
      by the addition of thrombin. We have studied contraction using human blood
      platelets, employing traction force microscopy, a single-cell technique that
      enables time-resolved measurements of cellular forces on soft substrates with
      elasticities in the physiological range (~4 kPa). We found that platelet
      contraction reaches a steady state after 25 min with total forces of ~34 nN.
      These forces are considerably larger than what was previously reported for
      platelets in aggregates, demonstrating the importance of a single-cell approach
      for studies of platelet contraction. Compared with other contractile cells, we
      find that platelets are unique, because force fields are nearly isotropic, with
      forces pointing toward the center of the cell area.

PMID- 22582080
TI  - MicroRNAs and Gastroenterological Cancers.
AB  - MicroRNAs are small noncoding RNAs that control gene expression. In doing so,
      they functionally contribute to the maintenance of cellular processes as well as
      several important features related to cancer development and progression such as
      cell growth control, differentiation and apoptosis. In fact, recent studies have
      shown that microRNAs are suitable and effective cancer-related biomarkers since
      they display altered expression profiles in cancers versus normal tissue. In
      addition, microRNAs have been associated with cancer progression and outcome. In
      this review, the current state of knowledge microRNA expression and function in
      relation to gastroenterological cancers will be addressed. Moreover, the
      mechanisms to alter their expression and the potential application of microRNAs
      in clinical settings will also be highlighted. Finally, the challenges involved
      in translating microRNA research to the clinic will be discussed.

PMID- 22582083
TI  - Agreement on Web-based Diagnoses and Severity of Mental Health Problems in
      Norwegian Child and Adolescent Mental Health Services.
AB  - OBJECTIVE: This study examined the agreement between diagnoses and severity
      ratings assigned by clinicians using a structured web-based interview within a
      child and adolescent mental health outpatient setting. METHOD: Information on 100
      youths was obtained from multiple informants through a web-based Development and
      Well-Being Assessment (DAWBA). Based on this information, four experienced
      clinicians independently diagnosed (according to the International Classification
      of Diseases Revision 10) and rated the severity of mental health problems
      according to the Health of the Nation Outcome Scales for Children and Adolescents
      (HoNOSCA) and the Children's Global Assessment Scale (C-GAS). RESULTS: Agreement
      for diagnosis was kappa=0.69-0.82. Intra-class correlation for single measures
      was 0.78 for HoNOSCA and 0.74 for C-GAS, and 0.93 and 0.92, respectively for
      average measures. CONCLUSIONS: Agreement was good to excellent for all diagnostic
      categories. Agreement for severity was moderate, but improved to substantial when
      the average of the ratings given by all clinicians was considered. Therefore, we
      conclude that experienced clinicians can assign reliable diagnoses and assess
      severity based on DAWBA data collected online.

PMID- 22582085
TI  - Cancer patients' experiences of using an Interactive Health Communication
      Application (IHCA).
AB  - Interactive Health Communication Applications (IHCAs) are increasingly used in
      health care. Studies document that IHCAs provide patients with knowledge and
      social support, enhance self- efficacy and can improve behavioural and clinical
      outcomes. However, research exploring patients' experiences of using IHCAs has
      been scarce. The aim of this study was to explore cancer patients' perspectives
      and experiences related to the use of an IHCA called WebChoice in their homes.
      Qualitative interviews were conducted with infrequent, medium and frequent IHCA
      users-six women and four men with breast and prostate cancer. The interviews were
      transcribed and analyzed inspired by interactionistic perspectives. We found that
      some patients' perceived WebChoice as a "friend," others as a "stranger." Access
      to WebChoice stimulated particularly high frequency users to position themselves
      as "information seeking agents," assuming an active patient role. However, to
      position oneself as an "active patient" was ambiguous and emotional. Feelings of
      "calmness", "normalization of symptoms", feelings of "being part of a community",
      feeling "upset" and "vulnerable", as well as "feeling supported" were identified.
      Interaction with WebChoice implied for some users an increased focus on illness.
      Our findings indicate that the interaction between patients and an IHCA such as
      WebChoice occurs in a variety of ways, some of which are ambivalent or
      conflicting. Particularly for frequent and medium frequency users, it offers
      support, but may at the same time reinforce an element of uncertainty in their
      life. Such insights should be taken into consideration in the future development
      of IHCAs in healthcare in general and in particular for implementation into
      patients' private sphere.

PMID- 22582084
TI  - CXCR2 signaling and host defense following coronavirus-induced encephalomyelitis.
AB  - Inoculation of the neurotropic JHM strain of mouse hepatitis virus (JHMV) into
      the central nervous system (CNS) of susceptible strains of mice results in wide
      spread replication within glial cells accompanied by infiltration of virus
      specific T lymphocytes that control virus through cytokine secretion and
      cytolytic activity. Virus persists within white matter tracts of surviving mice
      resulting in demyelination that is amplified by inflammatory T cells and
      macrophages. In response to infection, numerous cytokines/chemokines are secreted
      by resident cells of the CNS and inflammatory leukocytes that participate in both
      host defense and disease. Among these are the ELR-positive chemokines that are
      able to signal through CXC chemokine receptors including CXCR2. Early following
      JHMV infection, ELR-positive chemokines contribute to host defense by attracting
      CXCR2-expressing cells including polymorphonuclear cells to the CNS that aid in
      host defense through increasing the permeability the blood-brain-barrier (BBB).
      During chronic disease, CXCR2 signaling on oligodendroglia protects these cells
      from apoptosis and restricts the severity of demyelination. This review covers
      aspects related to host defense and disease in response to JHMV infection and
      highlights the different roles of CXCR2 signaling in these processes.

PMID- 22582086
TI  - Differences in substance-related risk behavior between dual and triple diagnosed
      severely mentally ill adults.
AB  - OBJECTIVES: The purpose of this study was to determine if differences exist
      between adults with dual and triple diagnoses with regard to substance-related
      risk behaviors.  METHODS: This secondary analysis was a cross-sectional study.
      There were 252 subjects with dual and triple diagnoses recruited from residential
      crisis programs in San Francisco. Using descriptive and logistic regression
      analyses, subjects in the two groups were compared with regard to demographic
      data, types of substances, and routes of administration used in the previous 30
      days to determine risk for exposure and/or transmission of HIV/HCV.  RESULTS:
      When compared to the dual diagnosis group, subjects with triple diagnoses were
      four times more likely to have engaged in IDU (p=.001) and 2.6 times more likely
      to use amphetamines (p=.05). They also reported using more types of substances
      over the lifetime (p<.0001). But with regard to other risk behaviors such as
      alcohol use to intoxication and cocaine/crack use, there were no significant
      differences.  CONCLUSION: Though many substance-related risk behaviors occurred
      in both groups, adults with triple diagnoses were more likely to engage in IDU,
      amphetamine use, and to use more types of substances over the lifetime. This
      information has the potential to inform interventions that might prevent/reduce
      substance-related risk in this population.

PMID- 22582087
TI  - Physiological aspects of cardiac tissue engineering.
AB  - Cardiac tissue engineering aims at repairing the diseased heart and developing
      cardiac tissues for basic research and predictive toxicology applications. Since
      the first description of engineered heart tissue 15 years ago, major development
      steps were directed toward these three goals. Technical innovations led to
      improved three-dimensional cardiac tissue structure and near physiological
      contractile force development. Automation and standardization allow medium
      throughput screening. Larger constructs composed of many small engineered heart
      tissues or stacked cell sheet tissues were tested for cardiac repair and were
      associated with functional improvements in rats. Whether these approaches can be
      simply transferred to larger animals or the human patients remains to be tested.
      The availability of an unrestricted human cardiac myocyte cell source from human
      embryonic stem cells or human-induced pluripotent stem cells is a major
      breakthrough. This review summarizes current tissue engineering techniques with
      their strengths and limitations and possible future applications.

PMID- 22582088
TI  - Bridging experiments, models and simulations: an integrative approach to
      validation in computational cardiac electrophysiology.
AB  - Computational models in physiology often integrate functional and structural
      information from a large range of spatiotemporal scales from the ionic to the
      whole organ level. Their sophistication raises both expectations and skepticism
      concerning how computational methods can improve our understanding of living
      organisms and also how they can reduce, replace, and refine animal experiments. A
      fundamental requirement to fulfill these expectations and achieve the full
      potential of computational physiology is a clear understanding of what models
      represent and how they can be validated. The present study aims at informing
      strategies for validation by elucidating the complex interrelations among
      experiments, models, and simulations in cardiac electrophysiology. We describe
      the processes, data, and knowledge involved in the construction of whole
      ventricular multiscale models of cardiac electrophysiology. Our analysis reveals
      that models, simulations, and experiments are intertwined, in an assemblage that
      is a system itself, namely the model-simulation-experiment (MSE) system. We argue
      that validation is part of the whole MSE system and is contingent upon 1)
      understanding and coping with sources of biovariability; 2) testing and
      developing robust techniques and tools as a prerequisite to conducting
      physiological investigations; 3) defining and adopting standards to facilitate
      the interoperability of experiments, models, and simulations; 4) and
      understanding physiological validation as an iterative process that contributes
      to defining the specific aspects of cardiac electrophysiology the MSE system
      targets, rather than being only an external test, and that this is driven by
      advances in experimental and computational methods and the combination of both.

PMID- 22582089
TI  - Maximizing the Power of Genome-Wide Association Studies: A Novel Class of
      Powerful Family-Based Association Tests.
AB  - For genome-wide association studies in family-based designs, a new, universally
      applicable approach is proposed. Using a modified Liptak's method, we combine the
      p-value of the family-based association test (FBAT) statistic with the p-value
      for the Van Steen-statistic. The Van Steen-statistic is independent of the FBAT
      statistic and utilizes information that is ignored by traditional FBAT
      approaches. The new test statistic takes advantages of all available information
      about the genetic association, while, by virtue of its design, it achieves
      complete robustness against confounding due to population stratification. The
      approach is suitable for the analysis of almost any trait type for which FBATs
      are available, e.g. binary, continuous, time to-onset, multivariate, etc. The
      efficiency and the validity of the new approach depend on the specification of a
      nuisance/tuning parameter and the weight parameters in the modified Liptak's
      method. For different trait types and ascertainment conditions, we discuss
      general guidelines for the optimal specification of the tuning parameter and the
      weight parameters. Our simulation experiments and an application to an Alzheimer
      study show the validity and the efficiency of the new method, which achieves
      power levels that are comparable to those of population-based approaches.

PMID- 22582091
TI  - Mindful awareness and non-judging in relation to posttraumatic stress disorder
      symptoms.
AB  - The objective of this cross-sectional study was to assess group differences
      between veterans with and without posttraumatic stress disorder (PTSD) in mindful
      awareness and mindful non-judging. The relationships between mindfulness and PTSD
      symptom clusters were also evaluated. Three age and gender-matched groups, 1)15
      combat veterans with PTSD, 2)15 combat veterans without PTSD, and 3) 15 non
      combat veterans without PTSD, completed the Mindful Attention Awareness Scale and
      the Accept without Judgment scale. PTSD status was determined with the Clinician
      Administered PTSD Scale and excluded disorders screened with the Structured
      Clinical Interview for DSM-IV. Mindfulness scale group differences were assessed
      with analysis of variance. Mindfulness and the PTSD symptom clusters
      relationships were assessed with hierarchical regression analysis. There were
      group differences on mindful non-judging (F(2,44)=7.22, p=.002) but not mindful
      awareness (p>.05). Combat exposure accounted for significant variation in PTSD
      symptoms (hyper-arousal 47%; numbing-avoiding 32%; re-experiencing 23%).
      Mindfulness accounted for a significant percentage variance of PTSD symptoms (re
      experiencing 32%; numbing-avoiding 19%, hyper-arousal 16%), beyond combat
      exposure effects, although only mindful non-judging was significant in the model.
      This study confirms in a clinical sample that mindful non-judging is associated
      with PTSD symptoms and could represent a meaningful focus for treatment.

PMID- 22582092
TI  - A Three-Dimensional Computational Fluid Dynamics Model of Regurgitant Mitral
      Valve Flow: Validation Against in vitro Standards and 3D Color Doppler Methods.

PMID- 22582090
TI  - Regenerating proteins and their expression, regulation and signaling.
AB  - The regenerating (Reg) protein family comprises C-type lectin-like proteins
      discovered independently during pancreatitis and pancreatic islet regeneration.
      However, an increasing number of studies provide evidence of participation of Reg
      proteins in the proliferation and differentiation of diverse cell types.
      Moreover, Reg family members are associated with various pathologies, including
      diabetes and forms of gastrointestinal cancer. These findings have led to the
      emergence of key roles for Reg proteins as anti-inflammatory, antiapoptotic and
      mitogenic agents in multiple physiologic and disease contexts. Yet, there are
      significant gaps in our knowledge regarding the regulation of expression of
      different Reg genes. In addition, the pathways relaying Reg-triggered signals,
      their targets and potential cross-talk with other cascades are still largely
      unknown. In this review, the expression patterns of different Reg members in the
      pancreas and extrapancreatic tissues are described. Moreover, factors known to
      modulate Reg levels in different cell types are discussed. Several signaling
      pathways, which have been implicated in conferring the effects of Reg ligands to
      date, are also delineated. Further efforts are necessary for elucidating the
      biological processes underlying the action of Reg proteins and their involvement
      in various maladies. Better understanding of the function of Reg genes and
      proteins will be beneficial in the design and development of therapies utilizing
      or targeting this protein group.

PMID- 22582094
TI  - Regulation and functional effects of ZNT8 in human pancreatic islets.
AB  - Zinc ions are essential for the formation of insulin crystals in pancreatic beta
      cells, thereby contributing to packaging efficiency of stored insulin. Zinc
      fluxes are regulated through the SLC30A (zinc transporter, ZNT) family. Here, we
      investigated the effect of metabolic stress associated with the prediabetic state
      (zinc depletion, glucotoxicity, and lipotoxicity) on ZNT expression and human
      pancreatic islet function. Both zinc depletion and lipotoxicity (but not
      glucotoxicity) downregulated ZNT8 (SLC30A8) expression and altered the glucose
      stimulated insulin secretion index (GSIS). ZNT8 overexpression in human islets
      protected them from the decrease in GSIS induced by tetrakis-(2-pyridylmethyl)
      ethylenediamine and palmitate but not from cell death. In addition, zinc
      supplementation decreased palmitate-induced human islet cell death without
      restoring GSIS. Altogether, we showed that ZNT8 expression responds to variation
      in zinc and lipid levels in human beta cells, with repercussions on insulin
      secretion. Prospects for increasing ZNT8 expression and/or activity may prove
      beneficial in type 2 diabetes in humans.

PMID- 22582093
TI  - Novel Role of Soluble Epoxide Hydrolase in Regulating Cholesterol in Mammalian
      Cells.
AB  - Soluble epoxide hydrolase (sEH) is becoming an attractive therapeutic target in
      cardiovascular disease. Recently, known human sEH polymorphisms were associated
      with elevated plasma cholesterol and atherosclerosis. In this study we evaluated
      the potential role of sEH in regulating cholesterol metabolism through modulating
      the levels of fatty acid epoxide substrates and/or their corresponding diol
      products known to activate peroxisome proliferator activated receptors (PPARs).
      We measured changes in cholesterol levels induced by expressing sEH proteins in
      mammalian cell lines and in response to treatment with various sEH-related
      compounds. Our results indicate that sEH has a cholesterol lowering effect that
      is mediated at least in part through its C-terminal hydrolase activity. In
      addition, several fatty acid epoxides and their corresponding diols showed
      cholesterol lowering effects in the current study. In conclusion, this study
      provides evidence that fatty acid epoxides and diols are endogenous cholesterol
      lowering molecules and that sEH may be involved in cholesterol regulation by
      modulating their levels.

PMID- 22582095
TI  - Enhancement of homocysteine toxicity to insulin-secreting BRIN-BD11 cells in
      combination with alloxan.
AB  - Previous studies have shown that homocysteine (HC) has a detrimental impact on
      insulin secretion and pancreatic beta cell function. The aim of the present study
      was to determine the role of reactive oxygen species (ROS) in the in vitro toxic
      effects of HC on insulin secretion and function of BRIN-BD11 insulin-secreting
      cells. In this study, insulin secretion from BRIN-BD11 cells was determined
      radioimmunologically, cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide assay and glucokinase activity by a glucose phosphorylation
      assay following culture with HC plus alloxan (Alx). Treatment with HC resulted in
      concentration-dependent inhibition of insulin secretion induced by glucose and
      other insulinotropic agents. HC in combination with Alx resulted in a more
      pronounced decline in insulin secretion, including that induced by 20  mM
      alanine, by 43% (P<0.001) and 30  mM KCl by 60% (P<0.001), compared with control
      culture. The glucokinase phosphorylating capacity in cells cultured with HC plus
      Alx was significantly lower, compared with control cells. The cells also
      displayed a significant 84% (P<0.001) decline in cell viability. Prolonged, 72-h
      culture of insulin-secreting cells with HC followed by 18-h culture without HC
      did not result in full restoration of beta cell responses to insulinotropic
      agents. In vitro oxygen consumption was enhanced by a combination of Alx with HC.
      The study arrived at the conclusion that HC generates ROS in a redox-cycling
      reaction with Alx that explains the decline in viability of insulin-secreting
      cells, leading to reduced glucokinase phosphorylating ability, diminished insulin
      secretory responsiveness and cell death.

PMID- 22582097
TI  - Hypothetical two-step initiation of experimental carcinogenesis by polycyclic
      aromatic hydrocarbons and aminoazo dyes.
AB  - A new hypothesis is discussed, which describes the initiation of the
      carcinogenesis through polycyclic aromatic hydrocarbons (PAHs) and aminoazo dyes
      (AZOs) as a two-step process: the oncogenic proteins of the ras or ras-like on
      cogenes activated by mutation ("initiation A ") co-operate with the complexes in
      the plasma membrane formed during the "initiation B " stage from the parent
      compounds of the PAHs or AZOs with cholesterol and apolipoprotein A-I. The final
      result of this co-operation, or the "complete initiation", is an irreversibly
      modified membrane architecture with negative consequences for growth control.

PMID- 22582096
TI  - Adiponectin inhibits KISS1 gene transcription through AMPK and specificity
      protein-1 in the hypothalamic GT1-7 neurons.
AB  - Adiponectin secreted from adipose tissues plays a role in the regulation of
      energy homeostasis, food intake, and reproduction in the hypothalamus. We have
      previously demonstrated that adiponectin significantly inhibited GNRH secretion
      from GT1-7 hypothalamic GNRH neuron cells. In this study, we further investigated
      the effect of adiponectin on hypothalamic KISS1 gene transcription, which is the
      upstream signal of GNRH. We found that globular adiponectin (gAd) or AICAR, an
      artificial AMPK activator, decreased KISS1 mRNA transcription and promoter
      activity. Conversely, inhibition of AMPK by Compound C or AMPKalpha1-SiRNA
      augmented KISS1 mRNA transcription and promoter activity. Additionally, gAd and
      AICAR decreased the translocation of specificity protein-1 (SP1) from cytoplasm
      to nucleus; however, Compound C and AMPKalpha1-siRNA played an inverse role. Our
      experiments in vivo demonstrated that the expression of Kiss1 mRNA was stimulated
      twofold in the Compound C-treated rats and decreased about 60-70% in gAd- or
      AICAR-treated rats compared with control group. The numbers of kisspeptin
      immunopositive neurons in the arcuate nucleus region of Sprague Dawley rats
      mimicked the same trend seen in Kiss1 mRNA levels in animal groups with different
      treatments. In conclusion, our results provide the first evidence that
      adiponectin reduces Kiss1 gene transcription in GT1-7 cells through activation of
      AMPK and subsequently decreased translocation of SP1.

PMID- 22582098
TI  - Survey of Virulence Determinants among Vancomycin Resistant Enterococcus faecalis
      and Enterococcus faecium Isolated from Clinical Specimens of Hospitalized
      Patients of North west of Iran.
AB  - Recent data indicates an increasing rate of vancomycin resistance in clinical
      enterococcal isolates worldwide. The nosocomial enterococci are likely to harbor
      virulence elements that increase their ability to colonize hospitalized patients.
      The aim of this study was to characterize virulence determinants in vancomycin
      resistant enterococci (VRE) obtained from various clinical sources.During the
      years 2008 to 2010, a total of 48 VRE isolates were obtained from three
      University teaching hospitals in Northwest, Iran. Initially, phenotypic
      speciation was done and minimum inhibitory concentrations (MICs) of vancomycin
      were determined by agar dilution method and E-test. Then, species identification
      and resistance genotypes along with detection of virulence genes (asa1, esp,
      gelE, ace and cpd) of the isolates were performed by multiplex PCR.Thirty eight
      isolates were identified as vancomycin-resistant Enterococcus faecium (VREfm) and
      ten as E. faecalis (VREfs). Irrespective of the species, vanA gene (89.58%) was
      dominant and three phenotypically vancomycin susceptible E. faecium isolates
      carried the vanB gene. Among virulence genes investigated, the esp was found in
      27(71%) VREfm strains, but did not in any VREfs. Other virulence determinants
      were highly detected in VREfs strains. Our data indicate a high prevalence of E.
      faecium harboring vancomycin resistance with vanA genotype and the two VRE
      species displayed different virulence genes.

PMID- 22582099
TI  - Assembly of synthetic locked phycocyanobilin derivatives with phytochrome in
      vitro and in vivo in Ceratodon purpureus and Arabidopsis.
AB  - Phytochromes are photoreceptors with a bilin chromophore in which light triggers
      the conversion between the red light-absorbing form, Pr, and the far-red-light
      absorbing form, Pfr. Here we performed in vitro and in vivo studies using locked
      phycocyanobilin derivatives, termed 15 Z anti phycocyanobilin (15ZaPCB) and 15 E
      anti PCB (15EaPCB). Recombinant bacterial and plant phytochromes incorporated
      either chromophore in a noncovalent or covalent manner. All adducts were
      photoinactive. The absorption spectra of the 15ZaPCB and 15EaPCB adducts were
      comparable with those of the Pr and Pfr form, respectively. Feeding of 15EaPCB,
      but not 15ZaPCB, to protonemal filaments of the moss Ceratodon purpureus resulted
      in increased chlorophyll accumulation, modulation of gravitropism, and induction
      of side branches in darkness. The effect of locked chromophores on phytochrome
      responses, such as induction of seed germination, inhibition of hypocotyl
      elongation, induction of cotyledon opening, randomization of gravitropism, and
      gene regulation, were investigated in wild-type Arabidopsis thaliana and the
      phytochrome-chromophore-deficient long hypocotyl mutant hy1. All phytochrome
      responses were induced in darkness by 15EaPCB, not only in the mutant but also in
      the wild type. These studies show that the 15Ea stereochemistry of the
      chromophore results in the formation of active Pfr-like phytochrome in the cell.
      Locked chromophores might be used to investigate phytochrome responses in many
      other organisms without the need to isolate mutants. The induction of phytochrome
      responses in the hy1 mutant by 15EaPCB were however less efficient than by red
      light irradiation given to biliverdin-rescued seeds or seedlings.

PMID- 22582100
TI  - A vacuolar beta-glucosidase homolog that possesses glucose-conjugated abscisic
      acid hydrolyzing activity plays an important role in osmotic stress responses in
      Arabidopsis.
AB  - The phytohormone abscisic acid (ABA) plays a critical role in various
      physiological processes, including adaptation to abiotic stresses. In Arabidopsis
      thaliana, ABA levels are increased both through de novo biosynthesis and via beta
      glucosidase homolog1 (BG1)-mediated hydrolysis of Glc-conjugated ABA (ABA-GE).
      However, it is not known how many different beta-glucosidase proteins produce ABA
      from ABA-GE and how the multiple ABA production pathways are coordinated to
      increase ABA levels. Here, we report that a previously undiscovered beta
      glucosidase homolog, BG2, produced ABA by hydrolyzing ABA-GE and plays a role in
      osmotic stress response. BG2 localized to the vacuole as a high molecular weight
      complex and accumulated to high levels under dehydration stress. BG2 hydrolyzed
      ABA-GE to ABA in vitro. In addition, BG2 increased ABA levels in protoplasts upon
      application of exogenous ABA-GE. Overexpression of BG2 rescued the bg1 mutant
      phenotype, as observed for the overexpression of NCED3 in bg1 mutants. Multiple
      Arabidopsis bg2 alleles with a T-DNA insertion in BG2 were more sensitive to
      dehydration and NaCl stress, whereas BG2 overexpression resulted in enhanced
      resistance to dehydration and NaCl stress. Based on these observations, we
      propose that, in addition to the de novo biosynthesis, ABA is produced in
      multiple organelles by organelle-specific beta-glucosidases in response to
      abiotic stresses.

PMID- 22582101
TI  - Phosphorylation of FAR-RED ELONGATED HYPOCOTYL1 is a key mechanism defining
      signaling dynamics of phytochrome A under red and far-red light in Arabidopsis.
AB  - Emerging plants have to adapt to a high ratio of far-red light (FR)/red light (R)
      light in the canopy before they reach the R-enriched direct sunlight. Phytochrome
      A (phyA) is the single dominant photoreceptor in young Arabidopsis thaliana
      seedlings that initiates photomorphogenesis in response to a FR-enriched
      environment and transduces increasing R signals to early responsive genes. To
      date, how phyA differentially transmits FR and R signals to downstream genes
      remains obscure. Here, we present a phyA pathway in which FAR-RED ELONGATED
      HYPOCOTYL1 (FHY1), an essential partner of phyA, directly guides phyA to target
      gene promoters and coactivates transcription. Furthermore, we identified two
      phosphorylation sites on FHY1, Ser-39 and Thr-61, whose phosphorylation by phyA
      under R inhibits phyA signaling at each step of its pathway. Deregulation of FHY1
      phosphorylation renders seedlings colorblind to FR and R. Finally, we show that
      the weaker phyA response resulting from FHY1 phosphorylation ensures the seedling
      deetiolation process in response to a R-enriched light condition. Collectively,
      our results reveal FHY1 phosphorylation as a key mechanism for FR/R spectrum
      specific responses in plants and an essential event for plant adaption to
      changing light conditions in nature.

PMID- 22582102
TI  - Efficacy of etoricoxib, celecoxib, lumiracoxib, non-selective NSAIDs, and
      acetaminophen in osteoarthritis: a mixed treatment comparison.
AB  - OBJECTIVE: To compare the efficacy of etoricoxib, lumiracoxib, celecoxib, non
      selective (ns) NSAIDs and acetaminophen in the treatment of osteoarthritis (OA) 
      METHODS: Randomized placebo controlled trials investigating the effects of
      acetaminophen 4000mg, diclofenac 150mg, naproxen 1000mg, ibuprofen 2400mg,
      celecoxib 100-400mg, lumiracoxib 100-400mg, and etoricoxib 30-60mg with treatment
      duration of at least two weeks were identified with a systematic literature
      search. The endpoints of interest were pain, physical function and patient global
      assessment of disease status (PGADS). Pain and physical function reported on
      different scales (VAS or LIKERT) were translated into effect sizes (ES). An ES
      0.2 - 0.5 was defined as a "small" treatment effect, whereas ES of 0.5 - 0.8 and
      > 0.8 were defined as "moderate" and "large", respectively. A negative effect
      indicated superior effects of the treatment group compared to the control group.
      Results of all trials were analyzed simultaneously with a Bayesian mixed
      treatment comparison. RESULTS: There is a >95% probability that etoricoxib (30 or
      60mg) shows the greatest improvement in pain and physical function of all
      interventions compared. ESs of etoricoxib 30mg relative to placebo, celecoxib
      200mg, ibuprofen 2400mg, and diclofenac 150mg were -0.66 (95% Credible Interval 
      0.83; -0.49), -0.32 (-0.50; -0.14), -0.25 (-0.53; 0.03), and -0.17 (-0.41; 0.08),
      respectively. Regarding physical functioning, ESs of etoricoxib 30mg relative to
      placebo, celecoxib 200mg, ibuprofen 2400mg, and diclofenac 150mg were -0.61 (
      0.76; -0.46), -0.27 (-0.43; -0.10), -0.20 (-0.47; 0.07), and -0.09 (- 0.33; 0.14)
      respectively. The greatest improvements in PGADS were expected with either
      etoricoxib or diclofenac. CONCLUSION: The current study estimated the efficacy of
      acetaminophen, nsNSAIDs, and COX-2 selective NSAIDs in OA and found that
      etoricoxib 30 mg is likely to result in the greatest improvements in pain and
      physical function. Differences in PGADS between interventions were smaller.

PMID- 22582103
TI  - Cost-effectiveness modelling of sequential biologic strategies for the treatment
      of moderate to severe rheumatoid arthritis in Finland.
AB  - OBJECTIVE: The main objective was to compare the cost-effectiveness of
      therapeutic options in moderate or severe rheumatoid arthritis (RA) when a
      clinical response to a first TNF-blocker, either etanercept (ETA), adalimumab
      (ADA), or infliximab (INF), is insufficient. METHODS: Effectiveness criteria were
      defined as remission (RS), low disease activity (LDAS), and moderate to high
      disease activity (MHDAS). Cost-effectiveness was derived as cost per day in RS
      and in LDAS using simulation modelling to assess six sequential biologic
      strategies over 2 years. Each sequential treatment strategy was composed of three
      biologic agents and included a first anti-TNF agent, ETA, ADA or INF, followed by
      either abatacept (ABA) or rituximab (RTX) as a second therapeutic option in case
      of an insufficient response, followed by another anti-TNF agent in case of
      further insufficient response. RESULTS: Over two years and taking into account
      biologic costs, the following estimated mean costs per day in RS and LDAS were
      respectively of ?829 and ?428 for the biologic sequence composed of ADA-ABA-ETA,
      ?1292 and ?516 for the sequence ADA-RTX-ETA, ?829 and ?429 for the sequence ETA
      ABA-ADA, ?1292 and ?517 for the sequence ETARTX- ADA, ?840 and ?434 for the
      sequence INF-ABA-ETA, and ?1309 and ?523 for the sequence INF-RTX-ETA.
      CONCLUSION: The treatment sequences including ABA as the second biologic option
      appear more cost-effective than those including RTX in a patients with moderate
      to severe RA and an insufficient response to a first anti-TNF agent.

PMID- 22582104
TI  - Ceramic femoral components in total knee arthroplasty - two year follow-up
      results of an international prospective multi-centre study.
AB  - BACKGROUND: Total knee arthroplasty can be considered as a reliable surgical
      procedure with a good long-term clinical result. However, implant failure due to
      particle induced aseptic loosening as well as the aspect of hypersensitivity to
      metal ions still remains an emerging issue. METHODS: The purpose of this
      prospective international multi-centre study was to evaluate the clinical and
      radiological outcomes and the reliability of the unconstrained Multigen Plus
      Total Knee System with a new BIOLOX(r) delta ceramic femoral component. Cemented
      total knee arthroplasty was performed on 108 patients (110 knees) at seven
      hospitals in three countries. Clinical and radiological evaluations were
      performed preoperatively, and after 3, 12 and 24 months postoperatively using the
      HSS-, WOMAC-, SF-36-score and standardised X-rays. RESULTS: The mean preoperative
      HSS-Score amounted to 55.5 +/- 11.5 points and improved significantly in all
      postoperative evaluations (85.7 +/- 11.7 points at 24 months). Furthermore,
      improvements in WOMAC- and SF-36-score were evaluated as significant at all
      points of evaluation. Radiolucent lines around the femoral ceramic component at
      24 months were found in four cases. Progression of radiolucent lines was not seen
      and no implant loosening was observed. During the 24 month follow-up eight
      patients underwent subsequent surgery due to reasons unrelated to the implant
      material. CONCLUSIONS: The observed clinical and radiological results are
      encouraging for a long-term survival of the ceramic femoral component. Therefore,
      ceramic implants could be a promising solution not only for patients with
      allergies against metallic implant materials, but also for the osteoarthritic
      knee joint. Long-term follow-up is necessary to draw conclusions regarding the
      superiority of the ceramic knee implants concerning in vivo wear and long-term
      survivorship.

PMID- 22582106
TI  - Genome Stability of Pandemic Influenza A (H1N1) 2009 Based on Analysis of
      Hemagglutinin and Neuraminidase Genes.
AB  - Influenza A virus (H1N1), which arose in 2009, constituted the fourth pandemic
      after the cases of 1918, 1957, and 1968. This new variant was formed by a triple
      reassortment, with genomic segments from swine, avian, and human influenza
      origins. The objective of this study was to analyze sequences of hemagglutinin
      (n=2038) and neuraminidase (n=1273) genes, in order to assess the extent of
      diversity among circulating 2009-2010 strains, estimate if these genes evolved
      through positive, negative, or neutral selection models of evolution during the
      pandemic phase, and analyze the worldwide percentage of detection of important
      amino acid mutations that could enhance the viral performance, such as
      transmissibility or resistance to drugs. A continuous surveillance by public
      health authorities will be critical to monitor the appearance of new influenza
      variants, especially in animal reservoirs such as swine and birds, in order to
      prevent the potential animal-human transmission of viruses with pandemic
      potential.

PMID- 22582105
TI  - Chronically HIV-1 Infected Patients Exhibit Low Frequencies of CD25+ Regulatory T
      Cells.
AB  - The characterization of regulatory T cells (Treg) during HIV infection has become
      of particular interest considering their potential role in the pathogenesis of
      the acquired immunodeficiency syndrome. Different reports on Tregs in HIV
      infected patients vary greatly, depending on the state of disease progression,
      anatomical compartment, and the phenotypic markers used to define this cell
      subpopulation. To determine the frequency of Tregs we included paired samples
      from peripheral blood and rectal biopsies from controls and chronic HIV patients
      with or without detectable viral load. Tregs were determined by flow cytometry
      using three different protocols: CD4(+)Foxp3(+); CD4(+)Foxp3(+)CD127(Low/-), and
      CD4(+)CD25(+)CD127(Low/-). In addition, and with the purpose to compare the
      different protocols we also characterized Tregs in peripheral blood of HIV
      negative individuals with influenza like symptoms. Here, we report that Treg
      characterization in HIV-infected patients as CD4(+)Foxp3(+) and
      CD4(+)Foxp3(+)CD127(Low/-) cells was similar, indicating that both protocols
      represent a suitable method to determine the frequency of Tregs in peripheral
      blood mononuclear cells (PBMC) and gut associated lymphoid tissue (GALT). In
      contrast, in HIV but not in flu-like patients, detection of Tregs as
      CD4(+)CD25(+)CD127(Low/- )cells resulted in a significantly lower percentage of
      these cells. In both, HIV patients and controls the frequency of Treg was
      significantly higher in GALT compared to PBMC. The frequency of Tregs in PBMC and
      GALT using CD4(+)Foxp3(+) and CD4(+)Foxp3(+)CD127(Low/-) was higher in HIV
      patients than in controls. Similarly, the frequency of Treg using any protocol
      was higher in flu-like patients compared to controls. The results suggest that
      relying on the expression of CD25 could be unsuitable to characterize Tregs in
      PBMC and GALT samples from a chronic infection such as HIV.

PMID- 22582107
TI  - Inverse cutting of posterior lamellar corneal grafts by a femtosecond laser.
AB  - PURPOSE: Posterior lamellar grafting of the cornea has become the preferred
      technique for treatment of corneal endothelial dysfunction. Posterior lamellar
      grafts are usually cut by a micro-keratome or a femto-second laser after the
      epithelial side of the donor cornea has been applanated. This approach often
      results in variable central graft thickness in different grafts and an increase
      in graft thickness towards the periphery in every graft. The purpose of this
      study was to evaluate if posterior lamellar grafts can be prepared from the
      endothelial side by a femto-second laser, resulting in reproducible, thin grafts
      of even thickness. METHODS: A CZM 500 kHz Visumax femto-second laser was used.
      Organ cultured donor grafts were mounted in an artifical anterior chamber with
      the endothelial side up and out. Posterior grafts of 7.8 mm diameter and 130
      micron thickness were prepared by femto-second laser cutting. A standard DSAEK
      procedure was performed in 10 patients with Fuchs endothelial dystrophy. Patients
      were followed-up regularly and evaluated by measurement of complications, visual
      acuity, corneal thickness (Pentacam HR), and endothelial cell density. RESULTS:
      Femto-laser cutting of grafts and surgery was uncomplicated. Rebubbling was
      necessary in 5 of 10 cases (normally only in 1 of 20 cases). All grafts were
      attached and cleared up during the first few weeks. After six months, the average
      visual acuity was 0.30 (range: 0.16 to 0.50), corneal thickness was 0.58 mm
      (range 0.51 to 0.63), and endothelial cell density was 1.570 per sq. mm (range:
      1.400 to 2.000 cells per sq. mm). The grafts were of uniform thickness, but
      substantial interface haze was present in most grafts. CONCLUSIONS: Posterior
      lamellar corneal grafts can be prepared from the endothelial side using a femto
      second laser. All grafts were clear after 6 months with satisfying endothelial
      cell counts. Poor visual acuity caused by interface scatter was observed in most
      patients. Femto-second laser cutting parameters needs to be optimised to enable
      smooth cutting in the posterior stroma.

PMID- 22582108
TI  - Information retrieval - Swedish specialist student nurses' strategies for finding
      clinical evidence.
AB  - The care that intra-operative nurses perform has to be based on scientific
      knowledge. It is therefore vitally important that they have access to different
      databases and the Internet, as well as knowledge of the search procedure to find
      evidence for best practice. This means that specialist nurses should be
      proficient in the search procedure, interpretation of data, and implementation of
      available knowledge.The aim of this study was therefore to highlight the search
      strategies of specialist student nurses for finding scientific knowledge with
      regard to specific clinical issues. An additional aim was to assess their ability
      to critically evaluate scientific articles. METHODS: The participants, n 16, all
      students enrolled in a university programme for specialist nursing in anaesthesia
      care, were required to find support for six questions, by using scientific
      knowledge databases. The tasks that required support are related to their future
      profession and were divided into three main areas: pre-, intra-, and post
      operative care. Two distinct questions for each main area had to be answered. The
      data was analysed quantitatively using manifest content analysis as a basis.
      RESULT: This study reveals that the student nurses mostly used the CINAHL and
      PubMed databases to search for answers related to the areas in focus. The
      keywords the participants used differed between the individuals and were applied
      more frequently than MESH terms. In addition, the critical evaluation of articles
      of scientific value that were found was not optimal. The study demonstrated that
      most of the participants were unable to complete all the required tasks. With
      regard to the initial questions, all 16 participants provided answers, while only
      eight student nurses completed the final questions. CONCLUSIONS: The specialist
      student nurses in this study used the databases Chinal and PubMed to find
      scientific knowledge with the help of MESH-terms and keywords. Further research
      is needed to understand how education of the specialist student nurses should be
      carried out, in order to optimise their search strategies and critical evaluation
      of scientific articles.

PMID- 22582109
TI  - Ready or Not: Predicting High and Low School Readiness Among Teen Parents'
      Children.
AB  - Past research has documented compromised development for teenage mothers'
      children compared to others, but less is known about predictors of school
      readiness among these children or among teenage fathers' children. Our
      multidimensional measures of high and low school readiness incorporated math,
      reading, and behavior scores and parent-reported health. Using parent interviews
      and direct assessments from the Early Childhood Longitudinal Study-Birth Cohort,
      we predicted high and low school readiness shortly before kindergarten among
      children born to a teenage mother and/or father (N~800). Factors from five
      structural and interpersonal domains based on the School Transition Model were
      measured at two time points, including change between those time points, to
      capture the dynamic nature of early childhood. Four domains (socioeconomic
      resources, maternal characteristics, parenting, and exposure to adults) predicted
      high or low school readiness, but often not both. Promising factors associated
      with both high and low readiness among teen parents' children came from four
      domains: maternal education and gains in education (socioeconomic), maternal age
      of at least 18 and fewer depressive symptoms (maternal characteristics),
      socioemotional parenting quality and home environment improvements (parenting),
      and living with fewer children and receiving nonparental child care in infancy
      (exposure to adults). The findings preliminarily suggest policies that might
      improve school readiness: encouraging maternal education while supplying child
      care, focusing teen pregnancy prevention efforts on school-age girls, basic
      socioeconomic supports, and investments in mental health and high-quality home
      environments and parenting.

PMID- 22582110
TI  - Real and hypothetical rewards.
AB  - Laboratory studies of choice and decision making among real monetary rewards
      typically use smaller real rewards than those common in real life. When
      laboratory rewards are large, they are almost always hypothetical. In applying
      laboratory results meaningfully to real-life situations, it is important to know
      the extent to which choices among hypothetical rewards correspond to choices
      among real rewards and whether variation of the magnitude of hypothetical rewards
      affects behavior in meaningful ways. The present study compared real and
      hypothetical monetary rewards in two experiments. In Experiment 1, participants
      played a temporal discounting game that incorporates the logic of a repeated
      prisoner's-dilemma (PD) type game versus tit-for-tat; choice of one alternative
      ("defection" in PD terminology) resulted in a small-immediate reward; choice of
      the other alternative ("cooperation" in PD terminology) resulted in a larger
      reward delayed until the following trial. The larger-delayed reward was greater
      for half of the groups than for the other half. Rewards also differed in type
      across groups: multiples of real nickels, hypothetical nickels or hypothetical
      hundred-dollar bills. All groups significantly increased choice of the larger
      delayed reward over the 40 trials of the experiment. Over the last 10 trials,
      cooperation was significantly higher when the difference between larger and
      smaller hypothetical rewards was greater. Reward type (real or hypothetical) made
      no significant difference in cooperation. In Experiment 2, real and hypothetical
      rewards were compared in social discounting - the decrease in value to the giver
      of a reward as social distance increases to the receiver of the reward. Social
      discount rates were well described by a hyperbolic function. Discounting rates
      for real and hypothetical rewards did not significantly differ. These results add
      to the evidence that results of experiments with hypothetical rewards validly
      apply in everyday life.

PMID- 22582111
TI  - Overgrowth of Rhodium on Gold Nanorods.
AB  - This study focuses on the deposition and growth mode of rhodium (Rh) on gold (Au)
      seed nanorods (NRs). Using a combination of scanning transmission electron
      microscopy imaging, energy-dispersive X-ray spectroscopy, and UV-visible
      absorption spectroscopy, we show that Rh deposition results in an uneven
      overlayer morphology on the Au NR seeds, with a tendency for Rh deposition to
      occur preferentially on the Au NR ends. The results suggest that complex and
      kinetically driven metal-metal interactions take place in this system.

PMID- 22582112
TI  - Glc-6-PD and PKG contribute to hypoxia-induced decrease in smooth muscle cell
      contractile phenotype proteins in pulmonary artery.
AB  - Persistent hypoxic pulmonary vasoconstriction (HPV) plays a significant role in
      the pathogenesis of pulmonary hypertension, which is an emerging clinical problem
      around the world. We recently showed that hypoxia-induced activation of glucose-6
      phosphate dehydrogenase (Glc-6-PD) in pulmonary artery smooth muscle links
      metabolic changes within smooth muscle cells to HPV and that inhibition of Glc
      6PD reduces acute HPV. Here, we demonstrate that exposing pulmonary arterial
      rings to hypoxia (20-30 Torr) for 12 h in vitro significantly (P < 0.05) reduces
      (by 30-50%) SM22alpha and smooth muscle myosin heavy chain expression and evokes
      HPV. Glc-6-PD activity was also elevated in hypoxic pulmonary arteries.
      Inhibition of Glc-6-PD activity prevented the hypoxia-induced reduction in
      SM22alpha expression and inhibited HPV by 80-90% (P < 0.05). Furthermore, Glc-6
      PD and protein kinase G (PKG) formed a complex in pulmonary artery, and Glc-6-PD
      inhibition increased PKG-mediated phosphorylation of VASP (p-VASP). In turn,
      increasing PKG activity upregulated SM22alpha expression and attenuated HPV
      evoked by Glc-6-PD inhibition. Increasing passive tension (from 0.8 to 3.0 g) in
      hypoxic arteries for 12 h reduced Glc-6-PD, increased p-VASP and SM22alpha
      levels, and inhibited HPV. The present findings indicate that increases in Glc-6
      PD activity influence PKG activity and smooth muscle cell phenotype proteins, all
      of which affect pulmonary artery contractility and remodeling.

PMID- 22582114
TI  - Therapeutic hypercapnia prevents bleomycin-induced pulmonary hypertension in
      neonatal rats by limiting macrophage-derived tumor necrosis factor-alpha.
AB  - Bleomycin-induced lung injury is characterized in the neonatal rat by
      inflammation, arrested lung growth, and pulmonary hypertension (PHT), as observed
      in human infants with severe bronchopulmonary dysplasia. Inhalation of CO(2)
      (therapeutic hypercapnia) has been described to limit cytokine production and to
      have anti-inflammatory effects on the injured lung; we therefore hypothesized
      that therapeutic hypercapnia would prevent bleomycin-induced lung injury.
      Spontaneously breathing rat pups were treated with bleomycin (1 mg/kg/d ip) or
      saline vehicle from postnatal days 1-14 while being continuously exposed to 5%
      CO(2) (Pa(CO(2)) elevated by 15-20 mmHg), 7% CO(2) (Pa(CO(2)) elevated by 35
      mmHg), or normocapnia. Bleomycin-treated animals exposed to 7%, but not 5%,
      CO(2), had significantly attenuated lung tissue macrophage influx and PHT, as
      evidenced by normalized pulmonary vascular resistance and right ventricular
      systolic function, decreased right ventricular hypertrophy, and attenuated
      remodeling of pulmonary resistance arteries. The level of CO(2) neither prevented
      increased tissue neutrophil influx nor led to improvements in decreased lung
      weight, septal thinning, impaired alveolarization, or decreased numbers of
      peripheral arteries. Bleomycin led to increased expression and content of lung
      tumor necrosis factor (TNF)-alpha, which was found to colocalize with tissue
      macrophages and to be attenuated by exposure to 7% CO(2). Inhibition of TNF-alpha
      signaling with the soluble TNF-2 receptor etanercept (0.4 mg/kg ip from days 1-14
      on alternate days) prevented bleomycin-induced PHT without decreasing tissue
      macrophages and, similar to CO(2), had no effect on arrested alveolar
      development. Our findings are consistent with a preventive effect of therapeutic
      hypercapnia with 7% CO(2) on bleomycin-induced PHT via attenuation of macrophage
      derived TNF-alpha. Neither tissue macrophages nor TNF-alpha appeared to
      contribute to arrested lung development induced by bleomycin. That 7% CO(2)
      normalized pulmonary vascular resistance and right ventricular function without
      improving inhibited airway and vascular development suggests that vascular
      hypoplasia does not contribute significantly to functional changes of PHT in this
      model.

PMID- 22582113
TI  - Osteopontin is an endogenous modulator of the constitutively activated phenotype
      of pulmonary adventitial fibroblasts in hypoxic pulmonary hypertension.
AB  - Increased cell proliferation and migration, of several cell types are key
      components of vascular remodeling observed in pulmonary hypertension (PH). Our
      previous data demonstrate that adventitial fibroblasts isolated from pulmonary
      arteries of chronically hypoxic hypertensive calves (termed PH-Fibs) exhibit a
      "constitutively activated" phenotype characterized by high proliferative and
      migratory potential. Osteopontin (OPN) has been shown to promote several cellular
      activities including growth and migration in cancer cells. We thus tested the
      hypothesis that elevated OPN expression confers the "activated" highly
      proproliferative and promigratory/invasive phenotype of PH-Fibs. Our results
      demonstrate that, both in vivo and ex vivo, PH-Fibs exhibited increased
      expression of OPN, as well as its cognate receptors, alpha(V)beta(3) and CD44,
      compared with control fibroblasts (CO-Fibs). Augmented OPN expression in PH-Fibs
      corresponded to their high proliferative, migratory, and invasive properties and
      constitutive activation of ERK1/2 and AKT signaling. OPN silencing via small
      interfering RNA or sequestering OPN production by specific antibodies led to
      decreased proliferation, migration, invasion, and attenuated ERK1/2, AKT
      phosphorylation in PH-Fibs. Furthermore, increasing OPN levels in CO-Fibs via
      recombinant OPN resulted in significant increases in their proliferative,
      migratory, and invasive capabilities to the levels resembling those of PH-Fibs.
      Thus our data suggest OPN as an essential contributor to the activated (highly
      proliferative, migratory, and proinvasive) phenotype of pulmonary adventitial
      fibroblasts in hypoxic PH.

PMID- 22582115
TI  - Activity and inhibition of prostasin and matriptase on apical and basolateral
      surfaces of human airway epithelial cells.
AB  - Prostasin is a membrane-anchored protease expressed in airway epithelium, where
      it stimulates salt and water uptake by cleaving the epithelial Na(+) channel
      (ENaC). Prostasin is activated by another transmembrane tryptic protease,
      matriptase. Because ENaC-mediated dehydration contributes to cystic fibrosis
      (CF), prostasin and matriptase are potential therapeutic targets, but their
      catalytic competence on airway epithelial surfaces has been unclear. Seeking
      tools for exploring sites and modulation of activity, we used recombinant
      prostasin and matriptase to identify substrate t-butyloxycarbonyl-l-Gln-Ala-Arg-4
      nitroanilide (QAR-4NA), which allowed direct assay of proteases in living cells.
      Comparisons of bronchial epithelial cells (CFBE41o-) with and without functioning
      cystic fibrosis transmembrane conductance regulator (CFTR) revealed similar
      levels of apical and basolateral aprotinin-inhibitable activity. Although
      recombinant matriptase was more active than prostasin in hydrolyzing QAR-4NA,
      cell surface activity resisted matriptase-selective inhibition, suggesting that
      prostasin dominates. Surface biotinylation revealed similar expression of
      matriptase and prostasin in epithelial cells expressing wild-type vs. DeltaF508
      mutated CFTR. However, the ratio of mature to inactive proprostasin suggested
      surface enrichment of active enzyme. Although small amounts of matriptase and
      prostasin were shed spontaneously, prostasin anchored to the cell surface by
      glycosylphosphatidylinositol was the major contributor to observed QAR-4NA
      hydrolyzing activity. For example, the apical surface of wild-type CFBE41o-
      epithelial cells express 22% of total, extractable, aprotinin-inhibitable, QAR
      4NA-hydrolyzing activity and 16% of prostasin immunoreactivity. In conclusion,
      prostasin is present, mature and active on the apical surface of wild-type and CF
      bronchial epithelial cells, where it can be targeted for inhibition via the
      airway lumen.

PMID- 22582117
TI  - A comparison of survival and secondary contraction in expanded versus
      conventional full-thickness skin grafts: an experimental study in rats.
AB  - AIM: The aim of this experimental study is based on a comparison between the
      effect of expanded versus nonexpanded full-thickness skin grafts (FTSGs) on
      survival and secondary wound contraction. METHODS: A total of 20 quadrangular
      shaped, full-thickness skin defects with dimensions of 2 * 3 cm were created on
      the backs of 10 rats. Two groups were specified in this study depending on the
      coverage of the aforementioned defect areas using expanded versus conventional
      full-thickness grafts (n = 10 per group). The survival area of each graft and the
      amount of graft/wound contraction (secondary contraction) were measured by
      computerized planimetry on days 0, 7, 30, and 90. RESULTS: The mean graft areas
      achieved were 5.8 +/- 0.6, 4.2 +/- 1.5, and 1.2 +/- 1.1 cm(2) (P < .001) in the
      expanded FTSGs group and 5.3 +/- 0.9, 3.3 +/- 1.3, and 0.98 +/- 0.8 cm(2) (P <
      .001) in the nonexpanded FTSGs group on days 7, 30, and 90, respectively. Graft
      area reductions (secondary contraction) were 1.7 +/- 0.9 and 2.1 +/- 1.2 cm(2) (P
      = .8) on day 30 and 2.1 +/- 1.3 and 2.86 +/- 0.8 cm(2) (P = .3) on day 90 in the
      expanded and nonexpanded groups, respectively. CONCLUSION: According to this
      study, FTSGs that were harvested from tissue expansion revealed biological
      behaviors that were comparable with those of conventional grafts.

PMID- 22582116
TI  - Ca2+ responses of pulmonary arterial myocytes to acute hypoxia require release
      from ryanodine and inositol trisphosphate receptors in sarcoplasmic reticulum.
AB  - In pulmonary arterial smooth muscle cells (PASMC), acute hypoxia increases
      intracellular Ca(2+) concentration ([Ca(2+)](i)) by inducing Ca(2+) release from
      the sarcoplasmic reticulum (SR) and Ca(2+) influx through store- and voltage
      operated Ca(2+) channels in sarcolemma. To evaluate the mechanisms of hypoxic
      Ca(2+) release, we measured [Ca(2+)](i) with fluorescent microscopy in primary
      cultures of rat distal PASMC. In cells perfused with Ca(2+)-free Krebs Ringer
      bicarbonate solution (KRBS), brief exposures to caffeine (30 mM) and
      norepinephrine (300 MUM), which activate SR ryanodine and inositol trisphosphate
      receptors (RyR, IP(3)R), respectively, or 4% O(2) caused rapid transient
      increases in [Ca(2+)](i), indicating intracellular Ca(2+) release. Preexposure of
      these cells to caffeine, norepinephrine, or the SR Ca(2+)-ATPase inhibitor
      cyclopiazonic acid (CPA; 10 MUM) blocked subsequent Ca(2+) release to caffeine,
      norepinephrine, and hypoxia. The RyR antagonist ryanodine (10 MUM) blocked Ca(2+)
      release to caffeine and hypoxia but not norepinephrine. The IP(3)R antagonist
      xestospongin C (XeC, 0.1 MUM) blocked Ca(2+) release to norepinephrine and
      hypoxia but not caffeine. In PASMC perfused with normal KRBS, acute hypoxia
      caused a sustained increase in [Ca(2+)](i) that was abolished by ryanodine or
      XeC. These results suggest that in rat distal PASMC 1) the initial increase in
      [Ca(2+)](i) induced by hypoxia, as well as the subsequent Ca(2+) influx that
      sustained this increase, required release of Ca(2+) from both RyR and IP(3)R, and
      2) the SR Ca(2+) stores accessed by RyR, IP(3)R, and hypoxia functioned as a
      common store, which was replenished by a CPA-inhibitable Ca(2+)-ATPase.

PMID- 22582118
TI  - Versatility of the anterolateral thigh free flap: the four seasons flap.
AB  - Presented at the following academic meetings:? 56th Meeting of the Italian
      Society of Plastic, Reconstructive and Aesthetic Surgery (SICPRE) Fasano
      (Brindisi), Italy, September 26-29, 2007? 42nd Meeting of the European Society
      for Surgical Research (ESSR), Warsaw, Poland, May 21-24, 2008? Winter Meeting,
      British Association of Plastic, Reconstructive and Aesthetic Surgeons, (BAPRAS)
      London, December 1-3, 2009BACKGROUND: The anterolateral free flap has become
      increasingly popular at our institution year on year. We decided to review our
      experience with this flap and study the reasons for this trend. METHODS: A
      retrospective review of all anterolateral thigh free flaps performed at
      Addenbrooke's University Hospital from the available charts was carried out. This
      chart review included patients' demographics, indications, flap size, recipient
      vessels used, ischemia time, flap, and donor site outcomes. All flap perforator
      vessels were located preoperatively using a handheld Doppler ultrasound probe.
      RESULTS: From October 1999 to December 2008, 55 anterolateral thigh flaps were
      performed in 55 patients to reconstruct a variety of soft-tissue defects (upper
      and lower limbs, chest wall, skull base, head and neck). Flap size ranged 12 to
      35 cm in length and 4 to 11 cm in width. During flap elevation, the main supply
      to the flap was found to be a direct septocutaneous perforator in 41% (n = 23) of
      the cases as opposed to a musculocutaneous perforator, which was found in 59% (n
      = 32). The mean ischemia time was 82 minutes (range, 62-103). The overall flap
      success rate was 100%. Two flaps were successfully salvaged after reexploration
      for venous congestion. The donor site morbidity was minimal. The mean follow-up
      time was 18 months (range, 2-48). DISCUSSION AND CONCLUSION: The anterolateral
      thigh free flap was found to be a very reliable flap (100% success) across a wide
      range of clinical indications. It facilitates microvascular anastomoses as
      evidenced by the short ischemia time. It provided ample skin with volume that
      could be tailored to the defect. These advantages have led to its widespread use
      by different consultants and trainees in our department.

PMID- 22582119
TI  - Patient satisfaction and surgeon experience: a follow-up to the reduction
      mammaplasty learning curve study.
AB  - BACKGROUND: While it is known that increasing surgeon experience is correlated
      with improved efficiency and safety in the reduction mammaplasty procedure, it is
      unclear whether these improvements lead to an erosion in patient satisfaction.
      METHODS: The authors distributed the Breast-Q questionnaire to all patients who
      underwent bilateral reduction mammaplasty at their institution between 1995 and
      2007. Univariate and multivariate analyses were performed to assess the
      relationship between postoperative patient satisfaction scores and surgeon
      experience, as well as to characterize those patients with particularly high or
      low satisfaction scores, in general. RESULTS: A total of 279 (26.1%) completed
      surveys were analyzed. No statistically significant erosion in either
      Satisfaction with Breasts (SWB) or Satisfaction with Outcomes (SWO) scores were
      witnessed with increasing surgeon experience or efficiency. Patients older than
      40 years demonstrated significantly higher SWB scores than younger patients (P =
      .004), while patients who suffered postoperative soft tissue necrosis
      demonstrated significantly lower SWB (P = .003) and SWO (P = .010) scores.
      CONCLUSIONS: Gains in operative efficiency with increasing surgeon experience do
      not appear to come at the expense of patient satisfaction in the reduction
      mammaplasty procedure. Younger patients and those who experience postoperative
      soft tissue necrosis appear to be at higher risk for reporting lower
      postoperative patient satisfaction scores.

PMID- 22582120
TI  - "The Times They Are a-Changin'".

PMID- 22582121
TI  - Bevacizumab-mediated interference with VEGF signaling is sufficient to induce a
      preeclampsia-like syndrome in nonpregnant women.
AB  - Preeclampsia (gestational proteinuric hypertension) complicates 5% to 8% of all
      pregnancies, and is a major cause of maternal and perinatal morbidity and
      mortality. It is a multisystem disorder specific to human pregnancy and the
      puerperium. Although the etiology is unknown, increasing evidence from both
      animal and human studies suggests that an imbalance in circulating pro-(vascular
      endothelial growth factor [VEGF], placental growth factor) and anti-angiogenic
      factors (soluble fms-like tyrosine kinase 1, soluble endoglin) may be important.
      Bevacizumab (Avastin(r); Genentech, South San Francisco, CA), a humanized
      recombinant monoclonal IgG antibody that binds VEGF, has been shown to inhibit
      endothelial cell proliferation, suppress angiogenesis, and shrink a variety of
      solid tumors. We present two cases of bevacizumab toxicity that mimic
      preeclampsia with a reversible syndrome characterized by acute-onset severe
      hypertension, proteinuria, central nervous system irritability (headache,
      photophobia, blurred vision, seizures), abnormal laboratory tests (elevated liver
      function tests, thrombocytopenia), and evidence of reversible posterior
      leukoencephalopathy on neuroimaging. In both cases, the clinical and laboratory
      manifestations returned to normal with discontinuation of bevacizumab therapy and
      supportive care. Bevacizumab toxicity can mimic preeclampsia in nonpregnant
      women. These data suggest that interference with VEGF signaling is sufficient to
      induce a preeclampsia-like syndrome in nonpregnant patients. VEGF signaling
      therefore appears to play a central role-perhaps the central role-in the
      pathogenesis of preeclampsia, and provides a potential biomarker for the
      prediction, prevention, and treatment of this dangerous disorder.

PMID- 22582122
TI  - Urinary spot albumin:creatinine ratio for documenting proteinuria in women with
      preeclampsia.
AB  - AIM: To assess whether a single urinary spot urinary albumin:creatinine ratio
      (ACR) can be used to estimate 24-hour urinary protein excretion in women with
      preeclampsia. METHODS: ACR and 24-hour urinary protein excretion were measured in
      50 consecutive patients with preeclampsia. ACR was determined in a spot midstream
      urine sample and the amount of protein excretion was quantified in a 24-hour
      urine collection performed the following day. The correlation between the spot
      ACR and 24-hour urine protein excretion was assessed, and the diagnostic value of
      ACR was expressed in terms of specificity and sensitivity. Receiver operating
      characteristic curve analysis was used to determine the best cutoff values of the
      spot ACR for mild preeclampsia (proteinuria >= 0.3 g/24 h) and severe
      preeclampsia (defined in China as proteinuria >= 2 g/24 h). RESULTS: A strong
      correlation was evident between the spot ACR and 24-hour urinary protein
      excretion (r = .938; P < .001). The optimal spot ACR cutoff point was 22.8
      mg/mmol for 0.3 g/24 h of protein excretion (mild preeclampsia) with a
      sensitivity and specificity of 82.4% and 99.4%, respectively, and 155.6 mg/mmol
      for 2 g/24 h of protein excretion (severe preeclampsia) with a sensitivity and
      specificity of 90.6% and 99.6%, respectively. CONCLUSIONS: Compared with 24-hour
      urinary protein excretion, the spot urinary ACR may be a simple, convenient, and
      accurate indicator of significant proteinuria in women with preeclampsia.

PMID- 22582123
TI  - Sexual function in elderly women: a review of current literature.
AB  - Although sexuality remains an important component of emotional and physical
      intimacy that most men and women desire to experience throughout their lives,
      sexual dysfunction in women is a problem that is not well studied. The prevalence
      of sexual dysfunction among all women is estimated to be between 25% and 63%; the
      prevalence in postmenopausal women is even higher, with rates between 68% and
      86.5%. Increasing recognition of this common problem and future research in this
      field may alter perceptions about sexuality, dismiss taboo and incorrect thoughts
      on sexual dysfunction, and spark better management for patients, allowing them to
      live more enjoyable lives.

PMID- 22582124
TI  - Comprehensive surgical staging for endometrial cancer.
AB  - Despite a shift from clinical to surgical staging of endometrial cancer in 1988,
      performance of comprehensive surgical staging for clinically early-stage
      endometrial cancer remains controversial. Low-, intermediate-, and high-risk
      groups have been defined pathologically. Herein, we describe the risks and
      benefits of comprehensive surgical staging. Comprehensive surgical staging is
      encouraged in high-risk histologies, whereas a method of triage should be used to
      determine who among the low-grade endometrioid histology may benefit from
      comprehensive staging.

PMID- 22582125
TI  - An In Vitro Diagnostic Multivariate Index Assay (IVDMIA) for Ovarian Cancer:
      Harvesting the Power of Multiple Biomarkers.
AB  - In this review, OVA1(r) (Vermillion, Inc., Austin, TX), the first in vitro
      diagnostic multivariate index assay (IVDMIA) of protein biomarkers cleared by the
      US Food and Drug Administration (FDA), is used to explain the concept behind
      IVDMIA, the use of multiple markers to improve clinical performance of a
      diagnostic tool, and the key considerations in the development of IVDMIA.

PMID- 22582126
TI  - Genetic testing for lynch syndrome, an inherited cancer of the bowel,
      endometrium, and ovary.
AB  - Genetic screening for the mismatch repair genes found in patients with Lynch
      syndrome leads to improvements in health outcomes among carriers and members of
      their family. Clinicians now have a simple and easily employed means of
      determining if an individual carries the genetic mutations found with Lynch
      syndrome. This article reviews the background and incidence of Lynch syndrome and
      presents screening criteria, including the use of Web-based algorithms to
      estimate the likelihood of an individual having inherited Lynch mutations.
      Comprehensive management plans based on individual risk and family history plus
      appropriate preventive measures are recommended. Primary care providers including
      obstetrician-gynecologists are encouraged to adopt a proactive, evidence-based
      approach to address patients and their relatives with Lynch syndrome.

PMID- 22582128
TI  - Cervical screening routines.

PMID- 22582127
TI  - New Success With Microbicides and Pre-Exposure Prophylaxis for Human
      Immunodeficiency Virus (HIV): Is Female-Controlled Prevention the Answer to the
      HIV Epidemic?
AB  - Women who cannot negotiate condom use with their partners, often due to
      socioeconomic factors and sexual abuse, have no means of preventing themselves
      from acquiring the human immunodeficiency virus (HIV). There is a need to develop
      HIV-preventive methods initiated and controlled by women. Microbicides and other
      pre-exposure prophylaxis may help fill that need. Although two decades of
      research on broad-spectrum microbicides have generally been disappointing, recent
      trials with HIV-specific agents have yielded promising initial results. A new era
      of clinical research involves novel biochemical prevention methods, including HIV
      specific vaginal microbicides and oral antiretroviral chemoprophylaxis drugs (pre
      exposure prophylaxis; PrEP) that may help provide more control for women.

PMID- 22582129
TI  - Alcohol and breast cancer.

PMID- 22582130
TI  - Antihypertensives in pregnancy.

PMID- 22582131
TI  - Snippets.

PMID- 22582132
TI  - Barley metallothioneins: MT3 and MT4 are localized in the grain aleurone layer
      and show differential zinc binding.
AB  - Metallothioneins (MTs) are low-molecular-weight, cysteine-rich proteins believed
      to play a role in cytosolic zinc (Zn) and copper (Cu) homeostasis. However,
      evidence for the functional properties of MTs has been hampered by methodological
      problems in the isolation and characterization of the proteins. Here, we document
      that barley (Hordeum vulgare) MT3 and MT4 proteins exist in planta and that they
      differ in tissue localization as well as in metal coordination chemistry.
      Combined transcriptional and histological analyses showed temporal and spatial
      correlations between transcript levels and protein abundance during grain
      development. MT3 was present in tissues of both maternal and filial origin
      throughout grain filling. In contrast, MT4 was confined to the embryo and
      aleurone layer, where it appeared during tissue specialization and remained until
      maturity. Using state-of-the-art speciation analysis by size-exclusion
      chromatography inductively coupled plasma mass spectrometry and electrospray
      ionization time-of-flight mass spectrometry on recombinant MT3 and MT4, their
      specificity and capacity for metal ion binding were quantified, showing a strong
      preferential Zn binding relative to Cu and cadmium (Cd) in MT4, which was not the
      case for MT3. When complementary DNAs from barley MTs were expressed in Cu- or Cd
      sensitive yeast mutants, MT3 provided a much stronger complementation than did
      MT4. We conclude that MT3 may play a housekeeping role in metal homeostasis,
      while MT4 may function in Zn storage in developing and mature grains. The
      localization of MT4 and its discrimination against Cd make it an ideal candidate
      for future biofortification strategies directed toward increasing food and feed
      Zn concentrations.

PMID- 22582135
TI  - Reexamining the Impact of Family Planning Programs on US Fertility: Evidence from
      the War on Poverty and the Early Years of Title X().
AB  - Almost 50 years after domestic US family planning programs began, their effects
      on childbearing remain controversial. Using the county-level roll-out of these
      programs from 1964 to 1973, this paper reevaluates their shorter and longer term
      effects on US fertility rates. I find that the introduction of family planning is
      associated with significant and persistent reductions in fertility driven both by
      falling completed childbearing and childbearing delay. Although federally funded
      family planning accounted for a small portion of the post-baby boom US fertility
      decline, my estimates imply that they reduced childbearing among poor women by 19
      to 30 percent. (JEL I38, J12, J13, J18).

PMID- 22582133
TI  - Analysis of Arabidopsis glucose insensitive growth mutants reveals the
      involvement of the plastidial copper transporter PAA1 in glucose-induced
      intracellular signaling.
AB  - Sugars play important roles in many aspects of plant growth and development,
      acting as both energy sources and signaling molecules. With the successful use of
      genetic approaches, the molecular components involved in sugar signaling have
      been identified and their regulatory roles in the pathways have been elucidated.
      Here, we describe novel mutants of Arabidopsis (Arabidopsis thaliana), named
      glucose insensitive growth (gig), identified by their insensitivity to high
      glucose (Glc)-induced growth inhibition. The gig mutant displayed retarded growth
      under normal growth conditions and also showed alterations in the expression of
      Glc-responsive genes under high-Glc conditions. Our molecular identification
      reveals that GIG encodes the plastidial copper (Cu) transporter PAA1 (for P(1B)
      type ATPase 1). Interestingly, double mutant analysis indicated that in high Glc,
      gig is epistatic to both hexokinase1 (hxk1) and aba insensitive4 (abi4), major
      regulators in sugar and retrograde signaling. Under high-Glc conditions, the
      addition of Cu had no effect on the recovery of gig/paa1 to the wild type,
      whereas exogenous Cu feeding could suppress its phenotype under normal growth
      conditions. The expression of GIG/PAA1 was also altered by mutations in the
      nuclear factors HXK1, ABI3, and ABI4 in high Glc. Furthermore, a transient
      expression assay revealed the interaction between ABI4 and the GIG/PAA1 promoter,
      suggesting that ABI4 actively regulates the transcription of GIG/PAA1, likely
      binding to the CCAC/ACGT core element of the GIG/PAA1 promoter. Our findings
      indicate that the plastidial Cu transporter PAA1, which is essential for plastid
      function and/or activity, plays an important role in bidirectional communication
      between the plastid and the nucleus in high Glc.

PMID- 22582136
TI  - Hydrophobic Interactions Improve Selectivity to ERalpha for Ben-zothiophene
      SERMs.
AB  - The discovery, pharmacology, and biophysical characterization of an ERalpha
      selective benzothiophene (BTPalpha) is described. BTPalpha (4) is a high affinity
      ligand with 140-fold greater selectivity for ERalpha (K(i)=0.25 nM) over ERbeta
      (K(i)=35 nM). In rodent models of estrogen action, BTPalpha blocks the effects of
      estrogen in the uterus but mimics the effects estrogen on bone. The basis of
      ERalpha selectivity for BTPalpha was evaluated by using protein crystallography
      and hydrogen/deuterium exchange (HDX) mass spectrometry. HDX data supports that
      the n-butyl chain of BTPalpha stabilizes helix 7 in ERalpha relative to that of
      ERbeta which we propose leads to an enhancement of affinity to the alpha receptor
      sub-type.

PMID- 22582134
TI  - Gene silencing in Arabidopsis spreads from the root to the shoot, through a
      gating barrier, by template-dependent, nonvascular, cell-to-cell movement.
AB  - Upward long-distance mobile silencing has been shown to be phloem mediated in
      several different solanaceous species. We show that the Arabidopsis (Arabidopsis
      thaliana) seedling grafting system and a counterpart inducible system generate
      upwardly spreading long-distance silencing that travels not in the phloem but by
      template-dependent reiterated short-distance cell-to-cell spread through the
      cells of the central stele. Examining the movement of the silencing front
      revealed a largely unrecognized zone of tissue, below the apical meristem, that
      is resistant to the silencing signal and that may provide a gating or protective
      barrier against small RNA signals. Using a range of auxin and actin transport
      inhibitors revealed that, in this zone, alteration of vesicular transport
      together with cytoskeleton dynamics prevented or retarded the spread of the
      silencing signal. This suggests that small RNAs are transported from cell to cell
      via plasmodesmata rather than diffusing from their source in the phloem.

PMID- 22582137
TI  - Anti-inflammatory Effect of a Cell-Penetrating Peptide Targeting the Nrf2/Keap1
      Interaction.
AB  - Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is increasingly recognized as
      a central regulator of multiple signaling pathways in inflammation and cancer,
      and the ability to use chemical biological tools to investigate its biological
      effects is very attractive. A peptide comprising a TAT-conjugated Nrf2 sequence
      is shown to activate Nrf2 and its downstream target gene heme-oxygenase-1 (HO-1)
      in a dose-dependent manner in intact human THP-1 monocytes. Levels of Nrf2
      protein peak after 3 h, whereas HO-1 mRNA and protein peak after 6 and 12 h,
      respectively. The peptide is also shown to inhibit the production of the pro
      inflammatory cytokine TNF. The TAT-14mer constitutes a useful chemical biology
      tool with potential therapeutic applications.

PMID- 22582139
TI  - Small Molecule Induction of Human Umbilical Stem Cells into MBP-positive
      Oligodendrocytes in a Defined Three-Dimensional Environment.
AB  - Stem cells from umbilical cord would be a favorable alternative to embryonic stem
      cells for therapeutic applications. In this study, human multipotent progenitor
      cells (MLPCs) from umbilical cord were differentiated into oligodendrocytes by
      exposure to a range of microenvironmental chemical and physical cues. Chemical
      cues were represented by a novel defined differentiation medium containing the
      neurotransmitter norepinephrine (NE). In traditional 2 dimensional (2D)
      conditions, the MLPCs differentiated into oligodendrocyte precursors, but did not
      progress further. However, in a 3 dimensional (3D) environment, the MLPCs
      differentiated into committed oligodendrocytes that expressed MBP. The apparent
      method of interaction of NE in stimulating the differentiation process was
      identified to occur through the adenergic pathway while all prior differentiation
      methods have used other routes. This novel method of obtaining functional human
      oligodendrocytes from MLPCs would eliminate many of the difficulties associated
      with their differentiation from embryonic stem cells.

PMID- 22582138
TI  - Neonatal citalopram treatment inhibits the 5-HT depleting effects of MDMA
      exposure in rats.
AB  - Neonatal exposure to 3,4-methylenedioxymethamphetamine (MDMA) produces long-term
      learning and memory deficits and increased anxiety-like behavior. The mechanism
      underlying these behavioral changes is unknown but we hypothesized that it
      involves perturbations to the serotonergic system as this is the principle mode
      of action of MDMA in the adult brain. During development 5-HT is a neurotrophic
      factor involved in neurogenesis, synaptogenesis, migration, and target region
      specification. We have previously showed that MDMA exposure (4*10 mg/kg/day) from
      P11-20 (analogous to human third trimester exposure) induces ~50% decreases in
      hippocampal 5-HT throughout treatment. To determine whether MDMA-induced 5-HT
      changes are determinative, we tested if these changes could be prevented by
      treatment with a selective serotonin reuptake inhibitor (citalopram: CIT). In a
      series of experiments we evaluated the effects of different doses and dose
      regimens of CIT on MDMA-induced 5-HT depletions in three brain regions
      (hippocampus, entorhinal cortex, and neostriatum) at three time-points (P12, P16,
      P21) during the treatment interval (P11-20) known to induce behavioral
      alterations when animals are tested as adults. We found that 5 mg/kg CIT
      administered twice daily significantly attenuated MDMA-induced 5-HT depletions in
      all three regions at all three ages but that the protection was not complete at
      all ages. Striatal dopamine was unaffected. We also found increases in
      hippocampal NGF and plasma corticosterone following MDMA treatment on P16 and
      P21, respectively. No changes in BDNF were observed. CIT treatment may be a
      useful means of interfering with MDMA-induced 5-HT reductions and thus permit
      tests of the hypothesis that the drug's cognitive and/or anxiety effects are
      mediated through early disruptions to 5-HT dependent developmental processes.

PMID- 22582140
TI  - Biomolecular surface construction by PDE transform.
AB  - This work proposes a new framework for the surface generation based on the
      partial differential equation (PDE) transform. The PDE transform has recently
      been introduced as a general approach for the mode decomposition of images,
      signals, and data. It relies on the use of arbitrarily high-order PDEs to achieve
      the time-frequency localization, control the spectral distribution, and regulate
      the spatial resolution. The present work provides a new variational derivation of
      high-order PDE transforms. The fast Fourier transform is utilized to accomplish
      the PDE transform so as to avoid stringent stability constraints in solving high
      order PDEs. As a consequence, the time integration of high-order PDEs can be done
      efficiently with the fast Fourier transform. The present approach is validated
      with a variety of test examples in two-dimensional and three-dimensional
      settings. We explore the impact of the PDE transform parameters, such as the PDE
      order and propagation time, on the quality of resulting surfaces. Additionally,
      we utilize a set of 10 proteins to compare the computational efficiency of the
      present surface generation method and a standard approach in Cartesian meshes.
      Moreover, we analyze the present method by examining some benchmark indicators of
      biomolecular surface, that is, surface area, surface-enclosed volume, solvation
      free energy, and surface electrostatic potential. A test set of 13 protein
      molecules is used in the present investigation. The electrostatic analysis is
      carried out via the Poisson-Boltzmann equation model. To further demonstrate the
      utility of the present PDE transform-based surface method, we solve the Poisson
      Nernst-Planck equations with a PDE transform surface of a protein. Second-order
      convergence is observed for the electrostatic potential and concentrations.
      Finally, to test the capability and efficiency of the present PDE transform-based
      surface generation method, we apply it to the construction of an excessively
      large biomolecule, a virus surface capsid. Virus surface morphologies of
      different resolutions are attained by adjusting the propagation time. Therefore,
      the present PDE transform provides a multiresolution analysis in the surface
      visualization. Extensive numerical experiment and comparison with an established
      surface model indicate that the present PDE transform is a robust, stable, and
      efficient approach for biomolecular surface generation in Cartesian meshes.

PMID- 22582141
TI  - Thermal controls on the Asian summer monsoon.
AB  - The Asian summer monsoon affects more than sixty percent of the world's
      population; understanding its controlling factors is becoming increasingly
      important due to the expanding human influence on the environment and climate and
      the need to adapt to global climate change. Various mechanisms have been
      suggested; however, an overarching paradigm delineating the dominant factors for
      its generation and strength remains debated. Here we use observation data and
      numerical experiments to demonstrates that the Asian summer monsoon systems are
      controlled mainly by thermal forcing whereas large-scale orographically
      mechanical forcing is not essential: the South Asian monsoon south of 20 degrees
      N by land-sea thermal contrast, its northern part by the thermal forcing of the
      Iranian Plateau, and the East Asian monsoon and the eastern part of the South
      Asian monsoon by the thermal forcing of the Tibetan Plateau.

PMID- 22582143
TI  - P190B RhoGAP Regulates Chromosome Segregation in Cancer Cells.
AB  - Rho GTPases are overexpressed and hyperactivated in many cancers, including
      breast cancer. Rho proteins, as well as their regulators and effectors, have been
      implicated in mitosis, and their altered expression promotes mitotic defects and
      aneuploidy. Previously, we demonstrated that p190B Rho GTPase activating protein
      (RhoGAP) deficiency inhibits ErbB2-induced mammary tumor formation in mice. Here
      we describe a novel role for p190B as a regulator of mitosis. We found that p190B
      localized to centrosomes during interphase and mitosis, and that it is
      differentially phosphorylated during mitosis. Knockdown of p190B expression in
      MCF-7 and Hela cells increased the incidence of aberrant microtubule-kinetochore
      attachments at metaphase, lagging chromosomes at anaphase, and micronucleation,
      all of which are indicative of aneuploidy. Cell cycle analysis of p190B deficient
      MCF-7 cells revealed a significant increase in apoptotic cells with a concomitant
      decrease in cells in G1 and S phase, suggesting that p190B deficient cells die at
      the G1 to S transition. Chemical inhibition of the Rac GTPase during mitosis
      reduced the incidence of lagging chromosomes in p190B knockdown cells to levels
      detected in control cells, suggesting that aberrant Rac activity in the absence
      of p190B promotes chromosome segregation defects. Taken together, these data
      suggest that p190B regulates chromosome segregation and apoptosis in cancer
      cells. We propose that disruption of mitosis may be one mechanism by which p190B
      deficiency inhibits tumorigenesis. 

PMID- 22582142
TI  - Statistical organelle dissection of Arabidopsis guard cells using image database
      LIPS.
AB  - To comprehensively grasp cell biological events in plant stomatal movement, we
      have captured microscopic images of guard cells with various organelles markers.
      The 28,530 serial optical sections of 930 pairs of Arabidopsis guard cells have
      been released as a new image database, named Live Images of Plant Stomata (LIPS).
      We visualized the average organellar distributions in guard cells using
      probabilistic mapping and image clustering techniques. The results indicated that
      actin microfilaments and endoplasmic reticulum (ER) are mainly localized to the
      dorsal side and connection regions of guard cells. Subtractive images of open and
      closed stomata showed distribution changes in intracellular structures, including
      the ER, during stomatal movement. Time-lapse imaging showed that similar ER
      distribution changes occurred during stomatal opening induced by light
      irradiation or femtosecond laser shots on neighboring epidermal cells, indicating
      that our image analysis approach has identified a novel ER relocation in stomatal
      opening.

PMID- 22582144
TI  - An Exploration of the Effect of Community Engagement in Research on Perceived
      Outcomes of Partnered Mental Health Services Projects().
AB  - Mental health research projects address sensitive issues for vulnerable
      populations and are implemented in complex environments. Community-Based
      Participatory Research approaches are recommended for health research on
      vulnerable populations, but little is known about how variation in participation
      affects outcomes of partnered research projects. We developed a conceptual model
      demonstrating the impact of community engagement in research on outcomes of
      partnered projects. We collected data on key constructs from community and
      academic leaders of 21 sampled partnered research projects in two cycles of an
      NIMH research center. We conducted empirical analyses to test the model. Our
      findings suggest that community engagement in research is positively associated
      with perceived professional development, as well as political and community
      impact.

PMID- 22582145
TI  - On-Bead Two-Color (OBTC) Cell Screen for Direct Identification of Highly
      Selective Cell Surface Receptor Ligands.
AB  - Combinatorial library screens can identify a suitable ligand for a biological
      target of interest out of thousands or even millions of compounds, and can play a
      key role in the modern drug development process. While conventional high
      throughput cell screens based on functional assays require expensive robotics,
      simple on-bead combinatorial assays for ligand binding to the target protein can
      be done far more cheaply. This article describes one such assay, developed using
      combinatorial peptoid libraries for targeting integral membrane receptors or
      other cell surface-exposed molecules. In addition to the reduced cost, a unique
      advantage of this assay is the direct identification of the most selective
      ligands for a cell surface receptor that is expressed in its natural environment.

PMID- 22582148
TI  - Transformation and analysis of tobacco plant var Petit havana with T-urf13 gene
      under anther-specific TA29 promoter.
AB  - T-urf13, a well-documented cms-associated gene from maize, has been shown to
      render methomyl sensitivity to heterologous systems like rice, yeast and bacteria
      when expressed constitutively. Since these transgenic plants were fertile, it was
      hypothesized that T-urf13 gene if expressed in anthers may result in male
      sterility that could be used for hybrid seed production. Hence, this work was
      aimed at analysing whether T-urf13 gene when expressed in anthers can result in
      male sterile plants or requires methomyl treatment to cause male sterility
      (controllable). This is the first report of transformation of tobacco with T
      urf13 gene under anther-specific promoter (TA29) with or without mitochondrial
      targeting sequence. Most of the transgenic plants obtained were fertile; this was
      surprising as many male sterile plants were expected as T-urf13 gene is a cms
      associated gene. Our results suggest that it may not be possible to obtain male
      sterility by expressing URF13 in the anther by itself or by methomyl application.

PMID- 22582146
TI  - Developing genetically engineered mouse models to study tumor suppression.
AB  - Since the late 1980s, the tools to generate mice with deletions of tumor
      suppressors have made it possible to study such deletions in the context of a
      whole animal. Deletion of some tumor suppressors results in viable mice while
      deletion of others yield embryo lethal phenotypes cementing the concept that
      genes that often go awry in cancer are also of developmental importance. More
      sophisticated mouse models were subsequently developed to delete a gene in a
      specific cell type at a specific time point. Additionally, incorporation of point
      mutations in a specific gene as observed in human tumors has also revealed their
      contributions to tumorigenesis. On the other hand, some models never develop
      cancer unless combined with other deletions suggesting a modifying role in
      tumorigenesis. This review will describe the technical aspects of generating
      these mice and provide examples of the outcomes obtained from alterations of
      different tumor suppressors.

PMID- 22582149
TI  - Alkalistable endo-beta-1,4-xylanase production from a newly isolated
      alkalitolerant Penicillium sp. SS1 using agro-residues.
AB  - Thermostable and alkalitolerant xylanases have got intense research focus due to
      their vast applications in various industries including pulp and paper, food,
      feed, textile, biofuel, etc. In the present investigation, a Penicillum sp. SS1
      isolated from degrading woody material was found to produce moderately
      thermoactive and alkalistable endo-beta-1,4-xylanase (xylanase). Maximum xylanase
      production was observed after fourth day of fermentation (43.84 IU/ml). The
      organism produced substantial quantities of xylanase using agricultural residues
      like wheat bran (20.6 IU/ml), rice bran (21.8 IU/ml) and sawdust (10.7 IU/ml) as
      carbon sources. The enzyme preparation was totally free of filter paper activity
      (FPase) and possessed negligible carboxymethyl cellulase (CMCase) activity; this
      could be an important feature of enzyme if the intended application of enzyme is
      in pulp and paper industries. Among nitrogen sources examined, yeast extract
      supported maximum xylanase production (45.74 IU/ml), and was followed by soybean
      meal (22.2 IU/ml) and ammonium sulphate (20 IU/ml). Maximum xylanase production
      was observed at initial medium pH 9 (25.6 IU/ml); however, at pH 8 and 10 also
      significantly high enzyme titre was observed (24 and 21.2 IU/ml, respectively).
      Thus, Penicillium sp. SS1 displayed capability of growing and producing xylanase
      at high alkaline pH (8-10). Maximum xylanase activity was reported at 50  degrees
      C, however, significantly high activity was observed at 60  degrees C (65.4%),
      however, at 70-80  degrees C activity was lost considerably. At 50-60  degrees C
      the enzyme retained very high activity up to 30-60 min (91-100%), however,
      prolonged incubation (90 min) caused considerable activity reduction (residual
      activity 63-68%).

PMID- 22582150
TI  - New microsatellite markers for assessment of genetic diversity in date palm
      (Phoenix dactylifera L.).
AB  - New primer pairs of genomic DNA microsatellite markers were tested to assess the
      genetic diversity of eleven date palm genotypes. The results indicated that out
      of thirty, only seven primers (23.3%) failed to amplify the expected PCR
      fragments, while thirteen primers (43.3%) amplified monomorphic banding patterns
      and the remaining ten primers (33.4%) generated polymorphic banding patterns. A
      total of 77 alleles have been observed with a mean of 7.7 alleles per locus. The
      average of gene diversity was 0.80 ranging from 0.6 (in marker DP168) to 0.9 (in
      two markers DP157 and DP175). These new co-dominant markers will be a starting
      point for researchers making use of the markers for genetic mapping and diversity
      analysis of date palm.

PMID- 22582147
TI  - Partner in fat metabolism: role of KLFs in fat burning and reproductive behavior.
AB  - The abnormalities caused by excess fat accumulation can result in pathological
      conditions which are linked to several interrelated diseases, such as
      cardiovascular disease and obesity. This set of conditions, known as metabolic
      syndrome, is a global pandemic of enormous medical, economic, and social concern
      affecting a significant portion of the world's population. Although genetics,
      physiology and environmental components play a major role in the onset of disease
      caused by excessive fat accumulation, little is known about how or to what extent
      each of these factors contributes to it. The worm, Caenorhabditis elegans offers
      an opportunity to study disease related to metabolic disorder in a developmental
      system that provides anatomical and genomic simplicity relative to the vertebrate
      animals and is an excellent eukaryotic genetic model which enable us to answer
      the questions concerning fat accumulation which remain unresolved. The stored
      triglycerides (TG) provide the primary source of energy during periods of food
      deficiency. In nature, lipid stored as TGs are hydrolyzed into fatty acids which
      are broken down through beta-oxidation to yield acetyl-CoA. Our recent study
      suggests that a member of C. elegans Kruppel-like factor, klf-3 regulates lipid
      metabolism by promoting FA beta-oxidation and in parallel may contribute in
      normal reproduction and fecundity. Genetic and epigenetic factors that influence
      this pathway may have considerable impact on fat related diseases in human.
      Increasing number of studies suggest the role of mammalian KLFs in adipogenesis.
      This functional conservation should guide our further effort to explore C.
      elegans as a legitimate model system for studying the role of KLFs in many
      pathway components of lipid metabolism.

PMID- 22582151
TI  - Removal of gaseous toluene using immobilized Candida tropicalis in a fluidized
      bed bioreactor.
AB  - A pure yeast strain Candida tropicalis was immobilized on the matrix of powdered
      activated carbon, sodium alginate, and polyethylene glycol (PSP beads). The
      immobilized beads were used as fluidized material in a bioreactor to remove
      toluene from gaseous stream. Applied toluene loadings were 15.4 and 29.8 g/m(3) h
      in Step 1 and Step 2, respectively, and toluene removal was found above 95%
      during the entire operation. A continuous pH decline was observed and pH of the
      suspension was just above 6 in Step 2 but no adverse effects on treatment
      efficiency were observed. The CO(2) yield values were found to be 0.57 and 0.62 g
      [Formula: see text] in Step 1 and Step 2, respectively. These values indicate
      that a major portion of toluene-carbon was channeled to yeast respiration even at
      higher toluene loading. In conclusion, immobilized C. tropicalis can be used as a
      fluidized material for enhanced degradation of gaseous toluene.

PMID- 22582152
TI  - Recent developments in mushrooms as anti-cancer therapeutics: a review.
AB  - From time immemorial, mushrooms have been valued by humankind as a culinary
      wonder and folk medicine in Oriental practice. The last decade has witnessed the
      overwhelming interest of western research fraternity in pharmaceutical potential
      of mushrooms. The chief medicinal uses of mushrooms discovered so far are as anti
      oxidant, anti-diabetic, hypocholesterolemic, anti-tumor, anti-cancer,
      immunomodulatory, anti-allergic, nephroprotective, and anti-microbial agents. The
      mushrooms credited with success against cancer belong to the genus Phellinus,
      Pleurotus, Agaricus, Ganoderma, Clitocybe, Antrodia, Trametes, Cordyceps,
      Xerocomus, Calvatia, Schizophyllum, Flammulina, Suillus, Inonotus, Inocybe,
      Funlia, Lactarius, Albatrellus, Russula, and Fomes. The anti-cancer compounds
      play crucial role as reactive oxygen species inducer, mitotic kinase inhibitor,
      anti-mitotic, angiogenesis inhibitor, topoisomerase inhibitor, leading to
      apoptosis, and eventually checking cancer proliferation. The present review
      updates the recent findings on the pharmacologically active compounds, their anti
      tumor potential, and underlying mechanism of biological action in order to raise
      awareness for further investigations to develop cancer therapeutics from
      mushrooms. The mounting evidences from various research groups across the globe,
      regarding anti-tumor application of mushroom extracts unarguably make it a fast
      track research area worth mass attention.

PMID- 22582153
TI  - Typing of Salmonella Typhi strains isolated from Egypt by RAPD PCR.
AB  - PCR-based fingerprinting using random amplified polymorphic DNA (RAPD) has been
      used widely for genome identification. In this study, 13 Salmonella Typhi strains
      were isolated from typhoid patients from Aswan, Cairo, Fayoum, and Monofya
      Governorates of Egypt. The isolates, along with three reference strains, i.e.,
      O901, H901, and Ty2 were subjected to whole genome typing by RAPD PCR. Three RAPD
      PCR 10-mer primers generated a total of 85 RAPD bands (81 polymorphic bands), 12
      distinct PCR profiles, and proved to be useful for discriminating the isolates
      and strains studied. Interestingly, the B(1) and C(1) PCR profile were found only
      in Cairo and Monofya, respectively; and some PCR types appeared only in certain
      Governorates of Egypt. By combining the profiles obtained with the primer trio
      used in this study, an excellent discrimination index (D) of 0.942 was reached.
      Pairwise comparisons of Jaccard's similarity coefficients calculated among the 12
      PCR types identified three major clusters; i.e., O901 branch and Ty2 and H901 sub
      branches. Principal component analysis adequately resolved each of these three
      major clusters. Three principal components accounted for about 72% of the
      variation, with the first two components accounting for about 62% of the total
      variance among the genotypes studied. Biclustering improved the display of groups
      of RAPD amplicons (markers) that cluster similarly across the genomes and could
      delineate features pertaining to genome structure. In conclusion, RAPD PCR
      provided a fast method with high potentials in surveillance and epidemiological
      investigations of Salmonella Typhi infections.

PMID- 22582154
TI  - Microwave assisted extraction of mangiferin from Curcuma amada.
AB  - Mangiferin present in Curcuma amada was extracted with the help of microwave
      assisted extraction (MAE). The extraction solvent used was ethanol, which is eco
      friendly and reduced the risk of environmental hazard. The mangiferin content was
      found to increase until 500 W, but decreased as the microwave power was increased
      further. A similar threshold was also obtained for microwave irradiation time.
      Following a mathematical analysis, an optimal mangiferin yield of 41 MUg/mL was
      obtained from an extraction time of 15.32 s for a microwave power of 500 W.

PMID- 22582155
TI  - In vitro plantlet regeneration from nodal segments and shoot tips of Capsicum
      chinense Jacq. cv. Naga King Chili.
AB  - An in vitro regeneration protocol was developed for Capsicum chinense Jacq. cv.
      Naga King Chili, a very pungent chili cultivar and an important horticultural
      crop of Nagaland (Northeast India). Maximum number of shoot (13 +/- 0.70) was
      induced with bud-forming capacity (BFC) index of 10.8, by culturing nodal
      segments in Murashige and Skoog (MS) medium supplemented with 18.16 MUM
      Thidiazuron (TDZ) followed by 35.52 MUM 6-benzylaminopurine (BAP). Using shoot
      tips as explants, multiple shoot (10 +/- 0.37) (BFC 8.3) was also induced in MS
      medium fortified with either 18.16 MUM TDZ or 35.52 MUM BAP. Elongated shoots
      were best rooted in MS medium containing 5.70 MUM indole-3-acetic acid (IAA).
      Rooted plantlets thus developed were hardened in 2-3 weeks time in plastic cups
      containing potting mixture of a 1:1 mix of soil and cow dung manure and then
      subsequently transferred to earthen pots. The regenerated plants did not show any
      variation in the morphology and growth as compared to the parent plant.

PMID- 22582156
TI  - Comparative studies of glycosylphosphatidylinositol-anchored high-density
      lipoprotein-binding protein 1: evidence for a eutherian mammalian origin for the
      GPIHBP1 gene from an LY6-like gene.
AB  - Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1
      (GPIHBP1) functions as a platform and transport agent for lipoprotein lipase
      (LPL) which functions in the hydrolysis of chylomicrons, principally in heart,
      skeletal muscle and adipose tissue capillary endothelial cells. Previous reports
      of genetic deficiency for this protein have described severe chylomicronemia.
      Comparative GPIHBP1 amino acid sequences and structures and GPIHBP1 gene
      locations were examined using data from several mammalian genome projects.
      Mammalian GPIHBP1 genes usually contain four coding exons on the positive strand.
      Mammalian GPIHBP1 sequences shared 41-96% identities as compared with 9-32%
      sequence identities with other LY6-domain-containing human proteins (LY6-like).
      The human N-glycosylation site was predominantly conserved among other mammalian
      GPIHBP1 proteins except cow, dog and pig. Sequence alignments, key amino acid
      residues and conserved predicted secondary structures were also examined,
      including the N-terminal signal peptide, the acidic amino acid sequence region
      which binds LPL, the glycosylphosphatidylinositol linkage group, the Ly6 domain
      and the C-terminal alpha-helix. Comparative and phylogenetic studies of mammalian
      GPIHBP1 suggested that it originated in eutherian mammals from a gene duplication
      event of an ancestral LY6-like gene and subsequent integration of exon 2, which
      may have been derived from BCL11A (B-cell CLL/lymphoma 11A gene) encoding an
      extended acidic amino acid sequence. ELECTRONIC SUPPLEMENTARY MATERIAL: The
      online version of this article (doi:10.1007/s13205-011-0026-4) contains
      supplementary material, which is available to authorized users.

PMID- 22582157
TI  - Bioreactor-based bioremediation of hydrocarbon-polluted Niger Delta marine
      sediment, Nigeria.
AB  - Crude oil-polluted marine sediment from Bonny River loading jetty Port Harcourt,
      Nigeria was treated in seven 2.5 l stirred-tank bioreactors designated BNPK,
      BNK5, BPD, BNO(3), BUNa, BAUT, and BUK over a 56-day period. Five bioreactors
      were biostimulated with either K(2)HPO(4), NH(4)NO(3), (NH(4))(2)SO(4), NPK, urea
      or poultry droppings while unamended (BUNa) and heat-killed (BAUT) treatments
      were controls. For each bioreactor, 1 kg (wet weight) sediment amended with 1 l
      seawater were spiked with 20 ml and 20 mg of crude oil and anthracene which gave
      a total petroleum hydrocarbons (TPH) range of 106.4-116 ppm on day 0. Polycyclic
      aromatic hydrocarbons (PAH) in all spiked sediment slurry ranged from 96.6 to
      104.4 ppm. TPH in each treatment was <=14.9 ppm while PAH was <=6.8 ppm by day
      56. Treatment BNO(3) recorded highest heterotrophic bacterial count (9.8 * 10(8)
      cfu/g) and hydrocarbon utilizers (1.15 * 10(8) cfu/g). By day 56, the percentages
      of biodegradation of PAHs, as measured with GC-FID were BNK5 (97.93%), BNPK
      (98.38%), BUK (98.82%), BUNa (98.13%), BAUT (93.08%), BPD (98.92%), and BNO(3)
      (98.02%). BPD gave the highest degradation rate for PAH. TPH degradation rates
      were as follows: BNK5 (94.50%), BNPK (94.77%), BUK (94.10%), BUNa (94.77%), BAUT
      (75.04%), BPD (95.35%), BNO(3) (95.54%). Fifty-six hydrocarbon utilizing
      bacterial isolates obtained were Micrococcus spp. 5 (9.62%), Staphylococcus spp.
      3 (5.78%), Pseudomonas spp. 7 (13.46%), Citrobacter sp. 1 (1.92%), Klebsiella sp.
      1 (1.92%), Corynebacterium spp. 5 (9.62%), Bacillus spp. 5 (9.62%), Rhodococcus
      spp. 7 (13.46%), Alcanivorax spp. 7 (13.46%), Alcaligenes sp. 1 (1.92%), Serratia
      spp. 2 (3.85%), Arthrobacter spp. 7 (13.46%), Nocardia spp. 2 (3.85%),
      Flavobacterium sp. 1 (1.92%), Escherichia sp. 1 (1.92%), Acinetobacter sp. 1
      (1.92%), Proteus sp. 1 (1.92%) and unidentified bacteria 10 (17%). These results
      indicate that the marine sediment investigated is amenable to bioreactor-based
      bioremediation and that abiotic factors also could contribute to hydrocarbon
      attenuation as recorded in the heat-killed (BAUT) control.

PMID- 22582158
TI  - Decolorization and partial mineralization of a polyazo dye by Bacillus firmus
      immobilized within tubular polymeric gel.
AB  - The degradation of C.I. Direct red 80, a polyazo dye, was investigated using
      Bacillus firmus immobilized by entrapment in tubular polymeric gel. This
      bacterial strain was able to completely decolorize 50 mg/L of C.I. Direct red 80
      under anoxic conditions within 12 h and also degrade the reaction intermediates
      (aromatic amines) during the subsequent 12 h under aerobic conditions. The
      tubular gel harboring the immobilized cells consisted of anoxic and aerobic
      regions integrated in a single unit which was ideal for azo dye degradation
      studies. Results obtained show that effective dye decolorization (97.8%),
      chemical oxygen demand (COD) reduction (91.7%) and total aromatic amines removal
      were obtained in 15 h with the immobilized bacterial cell system whereas for the
      free cells, a hydraulic residence time of 24 h was required for an equivalent
      performance in a sequential anoxic and aerobic process. Repeated-batch
      experiments indicate the immobilized cells could decolorize C.I. Direct red 80
      and reduce medium COD in five successive batch runs with enhanced activity
      obtained after each consecutive run, thus suggesting its stability and potential
      for repeated use in wastewater treatment. UV-visible spectrophotometry and HPLC
      analysis were used to confirm the partial mineralization of the dye. Data from
      this study could be used as a reference for the development of effective
      industrial scale biotechnological process for the removal of dyes and their
      metabolites in textile wastewater.

PMID- 22582159
TI  - Reduction of hexavalent chromium by Ochrobactrum intermedium BCR400 isolated from
      a chromium-contaminated soil.
AB  - Hexavalent chromium-resistant Ochrobactrum intermedium BCR400 was isolated from
      chromium contaminated soil collected from Vadodara, Gujarat. It reduced 100 mg
      Cr(VI)/L completely in 52 h with initial Cr(VI) reduction rate of 1.98 mg/L/h.
      The Cr(VI) reduction rate decreased with increase in Cr(VI) concentration from
      100 to 500 mg/L. The addition of anthraquinone-2-sulphonic acid (AQS) to culture
      O. intermedium BCR400 significantly enhanced its chromium reduction rate. The
      activation energy of AQS-mediated Cr(VI) reduction (120.69 KJ/mol) was 1.1-fold
      lower than non-mediated Cr(VI) reduction. An increase in the activities of
      quinone reductase and chromate reductase in cells grown in presence of AQS/AQS +
      Cr(VI) suggests their role in reduction of Cr(VI) by O. intermedium. Both
      chromate reductase and quinone reductase activities were FAD independent,
      required NADH as reductant, displayed maximum activity at pH (7.0) and
      temperature (30  degrees C). Thus Cr(VI) bioremediation potential of O.
      intermedium can be enhanced by augmentation of system with AQS as redox mediator.

PMID- 22582160
TI  - Mitogen-activated protein kinase phosphatase-1 modulates regional effects of
      injurious mechanical ventilation in rodent lungs.
AB  - RATIONALE: Mechanical ventilation induces heterogeneous lung injury by mitogen
      activated protein kinase (MAPK) and nuclear factor-kappaB. Mechanisms regulating
      regional injury and protective effects of prone positioning are unclear.
      OBJECTIVES: To determine the key regulators of the lung regional protective
      effects of prone positioning in rodent lungs exposed to injurious ventilation.
      METHODS: Adult rats were ventilated with high (18 ml/kg, positive end-expiratory
      pressure [PEEP] 0) or low Vt (6 ml/kg; PEEP 3 cm H(2)O; 3 h) in supine or prone
      position. Dorsal-caudal lung mRNA was analyzed by microarray and MAPK
      phosphatases (MKP)-1 quantitative polymerase chain reaction. MKP-1(-/-) or wild
      type mice were ventilated with very high (24 ml/kg; PEEP 0) or low Vt (6-7 ml/kg;
      PEEP 3 cm H(2)O). The MKP-1 regulator PG490-88 (MRx-108; 0.75 mg/kg) or phosphate
      buffered saline was administered preventilation. Injury was assessed by lung
      mechanics, bronchioalveolar lavage cell counts, protein content, and lung injury
      scoring. Immunoblotting for MKP-1, and IkappaBalpha and cytokine ELISAs were
      performed on lung lysates. MEASUREMENTS AND MAIN RESULTS: Prone positioning was
      protective against injurious ventilation in rats. Expression profiling
      demonstrated MKP-1 20-fold higher in rats ventilated prone rather than supine and
      regional reduction in p38 and c-jun N-terminal kinase activation. MKP-1(-/-) mice
      experienced amplified injury. PG490-88 improved static lung compliance and injury
      scores, reduced bronchioalveolar lavage cell counts and cytokine levels, and
      induced MKP-1 and IkappaBalpha. CONCLUSIONS: Injurious ventilation induces MAPK
      in an MKP-1-dependent fashion. Prone positioning is protective and induces MKP-1.
      PG490-88 induced MKP-1 and was protective against high Vt in a nuclear factor
      kappaB-dependent manner. MKP-1 is a potential target for modulating regional
      effects of injurious ventilation.

PMID- 22582162
TI  - Abnormal lung aging in chronic obstructive pulmonary disease and idiopathic
      pulmonary fibrosis.
AB  - Aging is a natural process characterized by progressive functional impairment and
      reduced capacity to respond appropriately to environmental stimuli and injury.
      The incidence of two common chronic respiratory diseases (chronic obstructive
      pulmonary disease [COPD] and idiopathic pulmonary fibrosis [IPF]) increases with
      advanced age. It is plausible, therefore, that abnormal regulation of the
      mechanisms of normal aging may contribute to the pathobiology of both COPD and
      IPF. This review discusses the available evidence supporting a number of aging
      mechanisms, including oxidative stress, telomere length regulation, cellular and
      immunosenescence, as well as changes in a number of antiaging molecules and the
      extracellular matrix, which are abnormal in COPD and/or IPF. A better
      understanding of these abnormalities may help in the design of novel and better
      therapeutic interventions for these patients.

PMID- 22582161
TI  - Prenatal and postnatal maternal stress and wheeze in urban children: effect of
      maternal sensitization.
AB  - RATIONALE: Critical periods for programming early wheeze risk may include
      pregnancy and infancy. Effects of timing remain poorly understood. OBJECTIVES:
      Associations among prenatal and postnatal maternal stress and children's wheeze
      were prospectively examined in 653 families. Effect modification by maternal
      sensitization was also examined. METHODS: Stress was indexed by a maternal
      negative life events (NLEs) score (range, 0-9) ascertained during pregnancy and
      between 1 and 2 years postpartum. Mothers reported child wheeze every 3 months up
      to age 2 years. Relationships of prenatal and postnatal maternal NLEs with
      repeated wheeze (>=2 episodes) were examined using logistic regression adjusting
      for covariates. Penalized splines were implemented to explore possible nonlinear
      associations. We also examined the interaction between prenatal stress and
      maternal sensitization indexed by allergen-specific IgE from maternal prenatal
      serum. MEASUREMENTS AND MAIN RESULTS: Adjusted models considering prenatal or
      postnatal NLEs alone both showed an exposure-response relationship between higher
      stress and child wheeze. When considering prenatal and postnatal stress
      concurrently, only children of mothers with high stress in both periods were
      significantly more likely to wheeze (adjusted odds ratio, 3.04; 95% confidence
      interval, 1.67-5.53) than children of mothers reporting low stress in both
      periods. Associations between high prenatal stress and wheeze were significant in
      children born to nonsensitized mothers (any IgE <0.35 kU/L) but not in the
      sensitized group (P for interaction = 0.03). CONCLUSIONS: Although children have
      heightened sensitivity to maternal stress in utero and in early childhood, those
      with higher stress in both periods were particularly at risk for wheeze. The
      prenatal maternal immune milieu modified effects.

PMID- 22582163
TI  - The case for increased funding for research in pulmonary and critical care.
AB  - The current economic and political climate places future funding of the National
      Institutes of Health (NIH) and other federal biomedical research programs in
      jeopardy. This Pulmonary Perspective seeks to arm the diverse membership of the
      American Thoracic Society with the information necessary to understand and
      articulate the value of biomedical research in their respective communities. We
      provide a historical overview of NIH funding in general and of allocations
      directed at respiratory-related research in particular. We argue that this is in
      fact an opportune time to expand investments in biomedical research and that
      doing so makes sense from the perspectives of improving health, curtailing health
      care expenditures, and job creation and economic growth. We further argue that
      current levels of allocation toward respiratory research are incommensurate with
      the medical, economic, and societal burden of respiratory disease in the United
      States. Respiratory disease currently is the only leading cause of death that has
      risen, rather than fallen, in recent decades. Declines in the burden of
      cardiovascular disease and cancer followed substantial increases in research
      funding, and slowing the rising burden of respiratory disease will likewise
      require a greatly expanded investment in pulmonary, critical care, and sleep
      research.

PMID- 22582164
TI  - Genomics and proteomics of vertebrate cholesterol ester lipase (LIPA) and
      cholesterol 25-hydroxylase (CH25H).
AB  - Cholesterol ester lipase (LIPA; EC 3.1.1.13) and cholesterol 25-hydroxylase
      (CH25H; EC 1.14.99.48) play essential role in cholesterol metabolism in the body
      by hydrolysing cholesteryl esters and triglycerides within lysosomes (LIPA) and
      catalysing the formation of 25-hydroxycholesterol from cholesterol (CH25H) which
      acts to repress cholesterol biosynthesis. Bioinformatic methods were used to
      predict the amino acid sequences, structures and genomic features of several
      vertebrate LIPA and CH25H genes and proteins, and to examine the phylogeny of
      vertebrate LIPA. Amino acid sequence alignments and predicted subunit structures
      enabled the identification of key sequences previously reported for human LIPA
      and CH25H and transmembrane structures for vertebrate CH25H sequences. Vertebrate
      LIPA and CH25H genes were located in tandem on all vertebrate genomes examined
      and showed several predicted transcription factor binding sites and CpG islands
      located within the 5' regions of the human genes. Vertebrate LIPA genes contained
      nine coding exons, while all vertebrate CH25H genes were without introns.
      Phylogenetic analysis demonstrated the distinct nature of the vertebrate LIPA
      gene and protein family in comparison with other vertebrate acid lipases and has
      apparently evolved from an ancestral LIPA gene which predated the appearance of
      vertebrates. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this
      article (doi:10.1007/s13205-011-0013-9) contains supplementary material, which is
      available to authorized users.

PMID- 22582166
TI  - Beyond pancreatic carcinoma: The close relationship between survivin levels and
      prognosis in systemic malignancies.
AB  - I read with great interest the recent article by Liu and Wang in a recent issue
      of your esteemed journal. The article is highly thought provoking. Interestingly,
      the past few years have seen a number of studies that have established a close
      relationship between survivin expression and tumor prognosis in systemic
      malignancies besides pancreatic carcinomas. For instance, a poor prognosis is
      seen in patients with bladder carcinomas which exhibit survivin over expression.
      A higher recurrence rate is seen following radio-chemotherapy in bladder
      carcinomas which exhibit increased survivin expression. Similarly, up regulation
      of survivin expression is seen in non-small cell lung cancers. In fact, Yamashita
      et al have shown that when used in combination with p53AIP1, survivin is a
      powerful prognostic indicator in non-small cell lung carcinomas. Similarly in
      breast carcinomas, increased survivin expression is more commonly seen in
      estrogen receptor negative carcinomas and is associated with a poor overall
      prognosis.

PMID- 22582165
TI  - A complete compilation of matrix metalloproteinase expression in human malignant
      gliomas.
AB  - Glioblastomas are characterized by an aggressive local growth pattern, a marked
      degree of invasiveness and poor prognosis. Tumor invasiveness is facilitated by
      the increased activity of proteolytic enzymes which are involved in destruction
      of the extracellular matrix of the surrounding healthy brain tissue. Elevated
      levels of matrix metalloproteinases (MMPs) were found in glioblastoma (GBM) cell
      lines, as well as in GBM biopsies as compared with low-grade astrocytoma (LGA)
      and normal brain samples, indicating a role in malignant progression. A careful
      review of the available literature revealed that both the expression and role of
      several of the 23 human MMP proteins is controversely discussed and for some
      there are no data available at all. We therefore screened a panel of 15 LGA and
      15 GBM biopsy samples for those MMPs for which there is either no, very limited
      or even contradictory data available. Hence, this is the first complete
      compilation of the expression pattern of all 23 human MMPs in astrocytic tumors.
      This study will support a better understanding of the specific expression
      patterns and interaction of proteolytic enzymes in malignant human glioma and may
      provide additional starting points for targeted patient therapy.

PMID- 22582167
TI  - FOXC1-associated phenotypes in humans may not always exhibit corneal
      neovascularization.

PMID- 22582168
TI  - Variability in encoding precision accounts for visual short-term memory
      limitations.
AB  - It is commonly believed that visual short-term memory (VSTM) consists of a fixed
      number of "slots" in which items can be stored. An alternative theory in which
      memory resource is a continuous quantity distributed over all items seems to be
      refuted by the appearance of guessing in human responses. Here, we introduce a
      model in which resource is not only continuous but also variable across items and
      trials, causing random fluctuations in encoding precision. We tested this model
      against previous models using two VSTM paradigms and two feature dimensions. Our
      model accurately accounts for all aspects of the data, including apparent
      guessing, and outperforms slot models in formal model comparison. At the neural
      level, variability in precision might correspond to variability in neural
      population gain and doubly stochastic stimulus representation. Our results
      suggest that VSTM resource is continuous and variable rather than discrete and
      fixed and might explain why subjective experience of VSTM is not all or none.

PMID- 22582169
TI  - Subpixel colocalization reveals amyloid precursor protein-dependent kinesin-1 and
      dynein association with axonal vesicles.
AB  - Intracellular transport of vesicles and organelles along microtubules is powered
      by kinesin and cytoplasmic dynein molecular motors. Both motors can attach to the
      same cargo and thus must be coordinated to ensure proper distribution of
      intracellular materials. Although a number of hypotheses have been proposed to
      explain how these motors are coordinated, considerable uncertainty remains, in
      part because of the absence of methods for assessing motor subunit composition on
      individual vesicular cargos. We developed a robust quantitative
      immunofluorescence method based on subpixel colocalization to elucidate relative
      kinesin-1 and cytoplasmic dynein motor subunit composition of individual,
      endogenous amyloid precursor protein (APP) vesicles in mouse hippocampal cells.
      The resulting method and data allow us to test a key in vivo prediction of the
      hypothesis that APP can recruit kinesin-1 to APP vesicles in neuronal axons. We
      found that APP levels are well-correlated with the amount of the light chain of
      kinesin-1 (KLC1) and the heavy chain of cytoplasmic dynein (DHC1) on vesicles. In
      addition, genetic reduction of APP diminishes KLC1 and DHC1 levels on APP cargos.
      Finally, our data reveal that reduction of KLC1 leads to decreased levels of DHC1
      on APP vesicles, suggesting that KLC1 is necessary for the association of DHC1 to
      these cargos, and help to explain previously reported retrograde transport
      defects generated when kinesin-1 is reduced.

PMID- 22582170
TI  - Distinct contributions of the amygdala and parahippocampal gyrus to suspicion in
      a repeated bargaining game.
AB  - Humans assess the credibility of information gained from others on a daily basis;
      this ongoing assessment is especially crucial for avoiding exploitation by
      others. We used a repeated, two-person bargaining game and a cognitive hierarchy
      model to test how subjects judge the information sent asymmetrically from one
      player to the other. The weight that they give to this information is the result
      of two distinct factors: their baseline suspicion given the situation and the
      suspicion generated by the other person's behavior. We hypothesized that human
      brains maintain an ongoing estimate of the credibility of the other player and
      sought to uncover neural correlates of this process. In the game, sellers were
      forced to infer the value of an object based on signals sent from a prospective
      buyer. We found that amygdala activity correlated with baseline suspicion,
      whereas activations in bilateral parahippocampus correlated with trial-by-trial
      uncertainty induced by the buyer's sequence of suggestions. In addition, the less
      credible buyers that appeared, the more sensitive parahippocampal activation was
      to trial-by-trial uncertainty. Although both of these neural structures have
      previously been implicated in trustworthiness judgments, these results suggest
      that they have distinct and separable roles that correspond to their theorized
      roles in learning and memory.

PMID- 22582171
TI  - Remote activation of biomolecules in deep tissues using near-infrared-to-UV
      upconversion nanotransducers.
AB  - Controlled activation or release of biomolecules is very crucial in various
      biological applications. Controlling the activity of biomolecules have been
      attempted by various means and controlling the activity by light has gained
      popularity in the past decade. The major hurdle in this process is that
      photoactivable compounds mostly respond to UV radiation and not to visible or
      near-infrared (NIR) light. The use of UV irradiation is limited by its toxicity
      and very low tissue penetration power. In this study, we report the exploitation
      of the potential of NIR-to-UV upconversion nanoparticles (UCNs), which act as
      nanotransducers to absorb NIR light having high tissue penetration power and
      negligible phototoxicity and emit UV light locally, for photoactivation of caged
      compounds and, in particular, used for photo-controlled gene expression. Both
      activation and knockdown of GFP was performed in both solution and cells, and
      patterned activation of GFP was achieved successfully by using upconverted UV
      light produced by NIR-to-UV UCNs. In-depth photoactivation through tissue
      phantoms and in vivo activation of caged nucleic acids were also accomplished.
      The success of this methodology has defined a unique level in the field of photo
      controlled activation and delivery of molecules.

PMID- 22582172
TI  - Variations in methanobactin structure influences copper utilization by methane
      oxidizing bacteria.
AB  - Methane-oxidizing bacteria are nature's primary biological mechanism for
      suppressing atmospheric levels of the second-most important greenhouse gas via
      methane monooxygenases (MMOs). The copper-containing particulate enzyme is the
      most widespread and efficient MMO. Under low-copper conditions methane-oxidizing
      bacteria secrete the small copper-binding peptide methanobactin (mbtin) to
      acquire copper, but how variations in the structures of mbtins influence copper
      metabolism and species selection are unknown. Methanobactins have been isolated
      from Methylocystis strains M and hirsuta CSC1, organisms that can switch to using
      an iron-containing soluble MMO when copper is limiting, and the nonswitchover
      Methylocystis rosea. These mbtins are shorter, and have different amino acid
      compositions, than the characterized mbtin from Methylosinus trichosporium OB3b.
      A coordinating pyrazinedione ring in the Methylocystis mbtins has little
      influence on the Cu(I) site structure. The Methylocystis mbtins have a sulfate
      group that helps stabilize the Cu(I) forms, resulting in affinities of
      approximately 10(21) M(-1). The Cu(II) affinities vary over three orders of
      magnitude with reduction potentials covering approximately 250 mV, which may
      dictate the mechanism of intracellular copper release. Copper uptake and the
      switchover from using the iron-containing soluble MMO to the copper-containing
      particulate enzyme is faster when mediated by the native mbtin, suggesting that
      the amino acid sequence is important for the interaction of mbtins with
      receptors. The differences in structures and properties of mbtins, and their
      influence on copper utilization by methane-oxidizing bacteria, have important
      implications for the ecology and global function of these environmentally vital
      organisms.

PMID- 22582173
TI  - Calpain inhibition preserves talin and attenuates right heart failure in acute
      pulmonary hypertension.
AB  - Right heart failure from right ventricular (RV) pressure overload is a major
      cause of morbidity and mortality, but its mechanism is incompletely understood.
      We tested the hypothesis that right heart failure during 4 hours of RV pressure
      overload is associated with alterations of the focal adhesion protein talin, and
      that the inhibition of calpain attenuates RV dysfunction and preserves RV talin.
      Anesthetized open-chest pigs treated with the calpain inhibitor MDL-28170 (n =
      20) or inactive vehicle (n = 23) underwent 4 hours of RV pressure overload by
      pulmonary artery constriction (initial RV systolic pressure, 64 +/- 1 and 66 +/-
      1 mm Hg in MDL-28170 and vehicle-treated pigs, respectively). Progressive RV
      contractile dysfunction was attenuated by MDL-28170: after 4 hours of RV pressure
      overload, RV systolic pressure was 44 +/- 4 mm Hg versus 49 +/- 6 mm Hg (P =
      0.011), and RV stroke work was 72 +/- 5% of baseline versus 90 +/- 5% of
      baseline, (P = 0.027), in vehicle-treated versus MDL-28170-treated pigs,
      respectively. MDL-28170 reduced the incidence of hemodynamic instability (death
      or systolic blood pressure of < 85 mm Hg) by 46% (P = 0.013). RV pressure
      overload disrupted talin organization. MDL-28170 preserved talin abundance in the
      RV free wall (P = 0.039), and talin abundance correlated with the maintenance of
      RV free wall stroke work (r = 0.58, P = 0.0039). alpha-actinin and vinculin
      showed similar changes according to immunohistology. Right heart failure from
      acute RV pressure overload is associated with reduced talin abundance and
      disrupted talin organization. Calpain inhibition preserves the abundance and
      organization of talin and RV function. Calpain inhibition may offer clinical
      utility in treating acute cor pulmonale.

PMID- 22582176
TI  - Advances in materials for room temperature hydrogen sensors.
AB  - Hydrogen (H(2)), as a source of energy, continues to be a compelling choice in
      applications ranging from fuel cells and propulsion systems to feedstock for
      chemical, metallurgical and other industrial processes. H(2), being a clean,
      reliable, and affordable source, is finding ever increasing use in distributed
      electric power generation and H(2) fuelled cars. Although still under 0.1%, the
      distributed use of H(2) is the fastest growing area. In distributed H(2) storage,
      distribution, and consumption, safety continues to be a critical aspect.
      Affordable safety systems for distributed H(2) applications are critical for the
      H(2) economy to take hold. Advances in H(2) sensors are driven by specificity,
      reliability, repeatability, stability, cost, size, response time, recovery time,
      operating temperature, humidity range, and power consumption. Ambient temperature
      sensors for H(2) detection are increasingly being explored as they offer
      specificity, stability and robustness of high temperature sensors with lower
      operational costs and significantly longer operational lifetimes. This review
      summarizes and highlights recent developments in room temperature H(2) sensors.

PMID- 22582174
TI  - Cellular FLICE-like inhibitory protein deviates myofibroblast fas-induced
      apoptosis toward proliferation during lung fibrosis.
AB  - A prominent feature of fibrotic tissue in general and of lungs in particular is
      fibroblast proliferation and accumulation. In patients overcoming fibrosis,
      apoptosis limits this excessive cell growth. We have previously shown resistance
      to Fas-induced apoptosis of primary lung fibroblasts from mice with bleomycin
      induced lung fibrosis, their escape from immune surveillance, and continued
      accumulation in spite of overexpression of the Fas death receptor. Cellular FLICE
      like inhibitory protein (c-FLIP) is a regulator of cell death receptor-induced
      apoptosis in many cell types. We aimed to determine c-FLIP levels in
      myofibroblasts from fibrotic lungs and to directly assess c-FLIP's role in
      apoptosis and proliferation of primary lung myofibroblasts. c-FLIP levels were
      determined by apoptosis gene array, flow cytometry, Western blot, and
      immunofluorescence before and after down-regulation with a specific small
      interfering RNA. Apoptosis was assessed by caspase cleavage in Western blot and
      by Annexin V affinity labeling after FACS and tissue immunofluorescence.
      Proliferation was assessed by BrdU uptake, also using FACS and
      immunofluorescence. We show that myofibroblasts from lungs of humans with
      idiopathic pulmonary fibrosis and from bleomycin-treated versus normal saline
      treated mice up-regulate c-FLIP levels. Using the animal model, we show that
      fibrotic lung myofibroblasts divert Fas signaling from apoptosis to proliferation
      and that this requires signaling by TNF receptor-associated factor (TRAF) and NF
      kappaB. c-FLIP down-regulation reverses the effect of Fas activation, causing
      increased apoptosis, decreased proliferation, and diminished recruitment of TRAF
      to the DISC complex. This indicates that c-FLIP is essential for myofibroblast
      accumulation and may serve as a potential target to manipulate tissue fibrosis.

PMID- 22582177
TI  - NSI and NSMT: usages of MS/MS fragment ion intensity for sensitive differential
      proteome detection and accurate protein fold change calculation in relative label
      free proteome quantification.
AB  - Although widely applied in the label-free quantification of proteomics, spectral
      count (SC)-based abundance measurements suffer from the narrow dynamic range of
      attainable ratios, leading to the serious underestimation of true protein
      abundance fold changes, especially when studying biological samples that exhibit
      very large fold changes in protein expression. MS/MS fragment ion intensity, as
      an alternative to SC, has recently gained acceptance as the abundance feature of
      protein in label-free proteomic studies. Herein, we implemented two formats of
      MS/MS fragment ion intensity, Spectral Index (SI) and Summed MS/MS TIC (SMT), to
      alleviate this particular deficiency arising from SC. Both were in forms of
      replacing SC in the Normalized Spectral Abundance Factor (NSAF) formula,
      resulting in two algorithms, abbreviated as NSI and NSMT, respectively. The
      necessity of the normalization process was validated using a publicly available
      dataset. Furthermore, when applied to another well characterized benchmark
      dataset, both NSI and NSMT showed improved overall accuracy over NSAF for the
      relative quantification of proteomes. Hereinto, NSI enabled the sensitive
      detection of differentially expressed proteins, while NSMT ensured accurate
      calculation for protein abundance fold change. Therefore, the selective use of
      both algorithms might facilitate the screening and quantification of potential
      biomarkers on the proteome scale.

PMID- 22582178
TI  - Porphyrin nanochannels reinforced by hydrogen bonding.
AB  - Carboxyl groups were introduced at the peripheral positions of
      dodecaphenylporphyrin to link nanochannel structures with intermolecular hydrogen
      bonds to make the supramolecular structures robust.

PMID- 22582179
TI  - Dissemination of systematic reviews in a hospital setting: a comparative survey
      for spreading use of the Cochrane Library.
AB  - INTRODUCTION: The Cochrane Library is the most important online evidence
      retrieval database of systematic reviews. Since 2007, the National Health
      Research Institutes has offered Taiwan's regional hospitals free access to the
      Cochrane Library. This study investigated how these hospitals disseminate its
      utilisation. METHODS: The usage rate of Cochrane reviews was measured in the
      participating hospitals from January 2008 to December 2009. Thereafter, a
      questionnaire survey was conducted for each regional hospital disseminator at the
      beginning of 2010 to analyse their methods of disseminating Cochrane reviews.
      RESULTS: The hospitals were stratified into three groups according to the
      relative rate of access: high (n=15), medium (n=16) and low (n=13). In comparison
      with the low-usage hospitals, the high-usage hospitals tended to assign a
      disseminator of evidence-based medicine to take charge of the dissemination of
      Cochrane reviews (p<0.001). In addition, the high-usage hospitals more often used
      the following six methods: providing relevant information via email (p<0.05),
      investing in early adopters (p<0.05), using assistance from designated personnel
      (p<0.05), highlighting the activity of early adopters (p<0.05), conducting
      workshops (p=0.001), and inviting experts to speak (p<0.001). There was no
      significant difference between high- and low-usage hospitals in organisational
      barriers. CONCLUSION: This study has identified several helpful strategies used
      by Taiwan's hospitals to enhance dissemination of the Cochrane Library, including
      raising of awareness, active delivery of information, mentoring relationships,
      and educational training. The data suggest that disseminating evidence-based
      medicine simultaneously is a key element.

PMID- 22582175
TI  - Protein kinase C-alpha and arginase I mediate pneumolysin-induced pulmonary
      endothelial hyperpermeability.
AB  - Antibiotics-induced release of the pore-forming virulence factor pneumolysin
      (PLY) in patients with pneumococcal pneumonia results in its presence days after
      lungs are sterile and is a major factor responsible for the induction of
      permeability edema. Here we sought to identify major mechanisms mediating PLY
      induced endothelial dysfunction. We evaluated PLY-induced endothelial
      hyperpermeability in human lung microvascular endothelial cells (HL-MVECs) and
      human lung pulmonary artery endothelial cells in vitro and in mice instilled
      intratracheally with PLY. PLY increases permeability in endothelial monolayers by
      reducing stable and dynamic microtubule content and modulating VE-cadherin
      expression. These events, dependent upon an increased calcium influx, are
      preceded by protein kinase C (PKC)-alpha activation, perturbation of the
      RhoA/Rac1 balance, and an increase in myosin light chain phosphorylation. At
      later time points, PLY treatment increases the expression and activity of
      arginase in HL-MVECs. Arginase inhibition abrogates and suppresses PLY-induced
      endothelial barrier dysfunction by restoring NO generation. Consequently, a
      specific PKC-alpha inhibitor and the TNF-derived tonoplast intrinsic protein
      peptide, which blunts PLY-induced PKC-alpha activation, are able to prevent
      activation of arginase in HL-MVECs and to reduce PLY-induced endothelial
      hyperpermeability in mice. Arginase I (AI)(+/-)/arginase II (AII)(-/-) C57BL/6
      mice, displaying a significantly reduced arginase I expression in the lungs, are
      significantly less sensitive to PLY-induced capillary leak than their wild-type
      or AI(+/+)/AII(-/-) counterparts, indicating an important role for arginase I in
      PLY-induced endothelial hyperpermeability. These results identify PKC-alpha and
      arginase I as potential upstream and downstream therapeutic targets in PLY
      induced pulmonary endothelial dysfunction.

PMID- 22582180
TI  - Who makes prescribing decisions in hospital inpatients? An observational study.
AB  - PURPOSE OF THE STUDY: Errors involving drug prescriptions are a key target for
      patient safety initiatives. Recent studies have focused on error rates across
      different grades of doctors in order to target interventions. However, many
      prescriptions are not instigated by the doctor who writes them. It is important
      to clarify how often this occurs in order to interpret these studies and create
      interventions. This study aimed to provisionally quantify and describe
      prescriptions where the identity of the decision maker and prescription writer
      differed. DESIGN OF THE STUDY: Observational data was collected in six wards, 2
      weeks per ward, at a single large UK teaching hospital over a 12-week period from
      January to April 2011. RESULTS: In 112/183 (61%) cases where a new medicine was
      prescribed, the decision maker was not the prescription writer. CONCLUSIONS:
      Decision making and the writing of prescriptions are generally not undertaken by
      the same doctor. Moreover, communication about prescriptions is poor. Further
      research in a larger sample of hospitals is required to confirm generalisability
      of the results, and to inform educational interventions to reduce error rates.

PMID- 22582181
TI  - In situ synthesis of stable mixed ligand Fe2+ complexes on bipyridinyl
      functionalized electrodes and nanotube supports.
AB  - A simple method is presented to synthesize asymmetric mixed ligand iron(II)
      diimine complexes using bipyridinyl functionalized carbon nanotubes. The
      synthesis of these complexes was realized using subsequent dip coating processes.
      The in situ formed mixed ligand complexes were used in aqueous media to act as
      building blocks in biosensor devices.

PMID- 22582182
TI  - Reactions of a methylzirconocene cation with phosphinoalkynes: an alternative
      pathway for generating Cp2Zr(II) systems.
AB  - A methylzirconocene cation (with a [B(C(6)F(5))(4)](-) counterion) transfers a
      methyl cation equivalent to diphenylphosphino-alkynes to generate (eta(2)
      alkyne)ZrCp(2) complexes bearing the [RC=CPPh(2)Me](+) ligand. Two examples of
      the PMe(3) ligand stabilized [(Me(3)P)Cp(2)Zr(eta(2)
      RC=CPPh(2)Me)(+)][B(C(6)F(5))(4)(-)] salts were characterized by X-ray
      diffraction.

PMID- 22582183
TI  - Impairments of prepulse inhibition of the startle response in abstinent alcoholic
      male patients.
AB  - AIMS: Prepulse inhibition (PPI) of the startle reflex, which refers to the
      ability of innocuous sensory events to reduce the startle reflex, has been
      described as an operational measure of sensorimotor gating that is reduced in
      several neuropsychiatric disorders, such as schizophrenia, but experience is
      lacking in addictions and alcoholism. The aim of this study was to examine the
      existence of impairments in the startle response and PPI in abstinent alcoholic
      men. METHODS: Testing for PPI was conducted on 60 abstinent alcoholic men aged 18
      65 years (mean 46.37) who met DSM-IV criteria for alcohol dependence and had been
      abstinent for more than a month at the time of testing. The comparison group were
      compared with 37 sex- age- and education-matched controls without alcohol
      dependence. RESULTS: Magnitudes of the startle reflex were lower in patients than
      in controls. The differences were statistically significant (P < 0.05) in trials
      with prepulses presented 30 and 120 ms before the onset of the startle stimulus.
      There was also a statistically significant (P < 0.05) reduced percentage of PPI
      when the prepulse was presented 30 ms before the startle stimulus. CONCLUSIONS:
      These data suggest that sensory information processing mechanisms could be
      damaged in abstinent alcoholic patients. The fact that these findings are common
      to other psychiatric disorders could indicate the existence of a common
      vulnerability marker and explain the high degree of comorbidity between
      alcoholism and other mental illnesses.

PMID- 22582184
TI  - Impaired generalization of associative learning in patients with alcohol
      dependence after intermediate-term abstinence.
AB  - AIMS: We used an associative learning task in order to investigate cognitive
      dysfunctions in alcohol dependence. This test is suitable for the assessment of
      stimulus-response learning and memory generalization (acquired equivalence),
      which is related to medial temporal lobe functioning. METHODS: Twenty patients
      with alcohol dependence (abstinence: >6 months) and 20 matched healthy controls
      participated in the study. In the task, antecedent stimuli were cartoon faces
      (girl, boy, man and woman) and consequent stimuli were color cartoon fishes. The
      task was to learn face-fish associations using feedback. In the transfer phase,
      the fish-face pairs were generalized to new associations. RESULTS: There was no
      significant difference between patients and controls during the acquisition phase
      of fish-face associations. In the transfer phase, patients were impaired relative
      to controls. We found no association between task performance and intelligence
      quotient. CONCLUSION: These results suggest that abstinent patients with alcohol
      dependence show marked dysfunctions in the generalization of associations, which
      may indicate the dysfunction of the medial temporal lobe.

PMID- 22582185
TI  - DRD2 C957T and TaqIA genotyping reveals gender effects and unique low-risk and
      high-risk genotypes in alcohol dependence.
AB  - AIMS: As recent conflicting reports describe a genetic association between both
      the C- and the T-alleles of the dopamine D2 receptor (DRD2) C957T polymorphism
      (rs6277) in alcohol-dependent subjects, our aim was to examine this polymorphism
      and TaqIA (rs1800497) in Australian alcohol-dependent subjects. METHODS: The
      C957T polymorphism was genotyped in 228 patients with alcohol dependence (72
      females and 156 males) and 228 healthy controls. RESULTS: The C-allele and C/C
      genotype of C957T was associated with alcohol dependence, whereas the TaqIA
      polymorphism was not. When analysed separately for C957T, males showed an even
      stronger association with the C-allele and females showed no association. The
      C957T and TaqIA haplotyping revealed a strong association with alcohol dependence
      and a double-genotype analysis (combining C957T and TaqIA genotypes) revealed
      that the relative risk of different genotypes varied by up to 27-fold with the
      TT/A1A2 having an 8.5-fold lower risk of alcohol dependence than other genotypes.
      CONCLUSION: Decreased DRD2 binding associated with the C-allele of the DRD2 C957T
      polymorphism is likely to be important in the underlying pathophysiology of at
      least some forms of alcohol dependence, and this effect appears to be limited to
      males only.

PMID- 22582186
TI  - N-Latex CDT results in liver diseases.
AB  - AIMS: The aim of this study was to test whether liver diseases of alcoholic and
      non-alcoholic origin cause false-positive carbohydrate-deficient transferrin
      (CDT) results when the particle-enhanced immunonephelometry for CDT assays is
      used and to assess the effect of liver disease severity on N-Latex CDT results.
      METHODS: Blood was sampled from 245 newly admitted patients suffering from liver
      diseases: alcoholic and non-alcoholic cirrhosis (AC), chronic viral (B and C) and
      non-viral hepatitis, toxic and autoimmune hepatitis (AIH), hepatocellular
      carcinoma and primary biliary cirrhosis (PBC). CDT was determined by particle
      enhanced imunononephelometry using the N-Latex CDT test. RESULTS: There were
      significant differences in %CDT levels between liver diseases of various
      etiologies. The %CDT level in AC was higher than that in chronic hepatitis (non
      viral and viral C). In turn, the %CDT level in chronic hepatitis C was lower than
      that in toxic hepatitis. The frequency of false-positive %CDT results in liver
      diseases of non-alcoholic origin was 13/146, and was highest in AIH (4/14). There
      were no CDT-positive results in PBC and chronic hepatitis B. The frequency of CDT
      positive results in alcoholic liver diseases was 24/59 in cirrhosis and 10/34 in
      hepatitis. Serum levels of %CDT in cirrhotic patients are correlated with the
      severity of the disease assessed by the Child-Pugh score. CONCLUSION: We
      concluded that the liver diseases affect the relative but not absolute values of
      CDT when using the assay with the monoclonal antibodies directed against CDT. The
      CDT results from N-Latex CDT test reflect the severity of liver dysfunction.

PMID- 22582187
TI  - One-step synthesis of silica@resorcinol-formaldehyde spheres and their
      application for the fabrication of polymer and carbon capsules.
AB  - Core@shell spheres made up of a thin layer of resorcinol-formaldehyde enveloping
      a silica core were prepared by means of a one-step method under Stober
      conditions. These spheres are used as a platform for the synthesis of carbon or
      polymeric capsules, and functionalized nanocomposites.

PMID- 22582188
TI  - Interface reactions and stability of a hydride composite (NaBH4 + MgH2).
AB  - The use of the interaction of two hydrides is a well-known concept used to
      increase the hydrogen equilibrium pressure of composite mixtures in comparison to
      that of pure systems. The thermodynamics and reaction kinetics of such hydride
      composites are reviewed and experimentally verified using the example NaBH(4) +
      MgH(2). Particular emphasis is placed on the measurement of the kinetics and
      stability using thermodesorption experiments and measurements of pressure
      composition isotherms, respectively. The interface reactions in the composite
      reaction were analysed by in situ X-ray photoelectron spectroscopy and by
      simultaneously probing D(2) desorption from NaBD(4) and H(2) desorption from
      MgH(2). The observed destabilisation is in quantitative agreement with the
      calculated thermodynamic properties, including enthalpy and entropy. The results
      are discussed with respect to kinetic limitations of the hydrogen desorption
      mechanism at interfaces. General aspects of modifying hydrogen sorption
      properties via hydride composites are given.

PMID- 22582191
TI  - EHR boat not ready to sail in United States.

PMID- 22582192
TI  - Osteopathic medical students' beliefs about osteopathic manipulative treatment at
      4 colleges of osteopathic medicine.

PMID- 22582193
TI  - Thanks, but no thanks: how denial of osteopathic service in the world wars shaped
      the profession-1.

PMID- 22582194
TI  - Thanks, but no thanks: how denial of osteopathic service in the world wars shaped
      the profession-2.

PMID- 22582196
TI  - Cardiac computed tomographic angiography and the primary care physician.
AB  - Through advancements in computer processing speed and storage capacity, new
      cardiac imaging modalities have become clinically feasible and useful. Cardiac
      computed tomographic angiography, a new diagnostic imaging modality, is capable
      of assessing coronary artery disease and left ventricular function on a par with
      invasive coronary arteriography in selected patients who meet appropriate use
      criteria. This imaging modality is of clinical value in the assessment of
      patients with chest pain who have an intermediate risk of coronary
      atherosclerosis. The purpose of the present report is to educate primary care
      physicians about the basic principles of advanced cardiac imaging techniques and
      to convey a useful strategy for their appropriate use in the current environment
      of medical economics.

PMID- 22582197
TI  - Efficacy of osteopathic manipulative treatment for low back pain in euhydrated
      and hypohydrated conditions: a randomized crossover trial.
AB  - CONTEXT: Low back pain (LBP) affects up to 85% of all persons at some time in
      life and is a condition for which osteopathic manipulative treatment (OMT) has
      been shown to be beneficial. Measures that can improve the efficacy of OMT would
      further benefit patients; one such measure, hydration status, was explored in
      this study. OBJECTIVE: To determine whether there is a relationship between a
      patient's hydration status before OMT for LBP and the outcome of that treatment.
      DESIGN: A randomized, single-blind crossover study conducted from March to
      December 2010. SETTING: Outpatient academic center. PARTICIPANTS: Eight women and
      11 men with LBP of 1 to 12 months duration. INTERVENTIONS: Both euhydrated and
      hypohydrated conditions were achieved in each participant by modifying water
      consumption for 36 hours before OMT sessions. PARTICIPANTS received 2 sessions of
      OMT, each in a different hydration condition and with a 1-week washout period in
      between. MAIN OUTCOME MEASURES: Pre- and posttreatment visual analog scale scores
      for pain, number and severity of somatic dysfunction as scored on the somatic
      dysfunction severity scale, and number of asymmetric landmarks found on the
      osteopathic standing structural examination. RESULTS: Improvements in total and
      severe number of lumbar somatic dysfunction (P=.001 and P=.013, respectively) and
      number of asymmetric landmarks on standing structural examination (P=.002) were
      found to be greater in the euhydrated vs the hypohydrated condition. PARTICIPANTS
      had a mean of 2 fewer areas of posttreatment somatic dysfunction when euhydrated
      than when hypohydrated, and they had a mean decrease of 2 asymmetric landmarks on
      the standing structural examination when euhydrated but none when hypohydrated.
      Osteopathic manipulative treatment improved self-reported pain immediately after
      treatment regardless of hydration status. CONCLUSION: Outcome measures improved
      for all participants, with greater improvement observed after participants were
      treated in the euhydrated condition than when in the hypohydrated condition. It
      is reasonable for clinicians to recommend that patients increase their hydration
      to optimize treatment.

PMID- 22582198
TI  - Iliacus tender points in young adults: a pilot study.
AB  - CONTEXT: Recent studies have assessed iliacus tender point prevalence in
      outpatient clinics. However, studies on the prevalence of iliacus tender points
      in the young adult population and the correlation of its prevalence with daily
      activities are lacking. OBJECTIVES: (1) To determine the prevalence of low back
      pain, iliacus tender points, and positive results of Thomas tests (ie, hypertonic
      iliopsoas muscles) in young adult participants. (2) To evaluate daily activities
      including prolonged sitting, exercise, and running or biking as predictive
      factors for low back pain, iliacus tender points, and positive Thomas test
      results. (3) To examine the relationship between iliacus tender points and
      positive Thomas test results. METHODS: Healthy students aged 18 to 30 years at
      Edward Via College of Osteopathic Medicine-Virginia Campus were recruited using e
      mail, class announcements, and flyers. Data were collected for age, sex, amount
      of time spent sitting in a 24-hour period, type and frequency of exercise
      performed, and low back pain in the past 7 days. Patients underwent an iliacus
      tender point assessment and a Thomas test; results of each were recorded for the
      right and left sides. RESULTS: Twenty-five women and 24 men aged 22 to 30 years
      (mean, 24.39 years) were analyzed. Twenty-four participants (49%) had low back
      pain, 46 (94%) had an iliacus tender point, and 25 (51%) had a positive Thomas
      test result. There was no statistically significant difference between men and
      women with regard to low back pain, tender point presence, or a positive Thomas
      test result (P=.26, .99, and .78, respectively). Participants who reported
      sitting for 8 or more hours in a 24-hour period or who reported running or biking
      more than 3 times per week were more likely to have an iliacus tender point
      (P=.001 and .028, respectively). CONCLUSION: The prevalence of iliacus tender
      points was high in the study population. Prolonged sitting and running or biking
      was associated with an increased risk of developing low back pain or an iliacus
      tender point.

PMID- 22582199
TI  - Fatal venous thromboembolism after splenectomy: pathogenesis and management.
AB  - Venous thromboembolism (VTE) occurs in approximately 10% of patients after
      splenectomy, particularly splenectomy performed for hematologic abnormalities.
      Clinicians often fail to recognize this potential complication in the
      postoperative period, leading to inappropriate anticoagulation prophylaxis and
      treatment for these patients. The authors discuss the pathophysiologic mechanisms
      of VTE in patients who undergo splenectomy and offer management strategies for
      this complication. A case report of a patient who underwent splenectomy for
      idiopathic thrombocytopenia purpura, with subsequent fatal VTE, highlights the
      importance of this issue. The authors also review current guidelines for managing
      venous thromboprophylaxis in patients who undergo general, laparoscopic, and
      cancer-related surgical procedures, and they compare these patients to those who
      undergo splenectomy.

PMID- 22582200
TI  - Efficacy of a physician's words of empathy: an overview of state apology laws.
AB  - Apology laws are gaining traction in the United States, prompting health care
      professionals to offer words of condolence for adverse medical outcomes without
      the fear of being sued for malpractice. Although these laws vary by jurisdiction,
      they have been shown to reduce the financial consequences of a medical
      malpractice lawsuit. The authors provide an overview of the laws regarding this
      issue and discuss apologies as a means to reduce medical malpractice claims.

PMID- 22582201
TI  - Erythema chronicum migrans.

PMID- 22582202
TI  - Development and evaluation of a crowdsourcing methodology for knowledge base
      construction: identifying relationships between clinical problems and
      medications.
AB  - OBJECTIVE: We describe a novel, crowdsourcing method for generating a knowledge
      base of problem-medication pairs that takes advantage of manually asserted links
      between medications and problems. METHODS: Through iterative review, we developed
      metrics to estimate the appropriateness of manually entered problem-medication
      links for inclusion in a knowledge base that can be used to infer previously
      unasserted links between problems and medications. RESULTS: Clinicians manually
      linked 231,223 medications (55.30% of prescribed medications) to problems within
      the electronic health record, generating 41,203 distinct problem-medication
      pairs, although not all were accurate. We developed methods to evaluate the
      accuracy of the pairs, and after limiting the pairs to those meeting an estimated
      95% appropriateness threshold, 11,166 pairs remained. The pairs in the knowledge
      base accounted for 183,127 total links asserted (76.47% of all links).
      Retrospective application of the knowledge base linked 68,316 medications not
      previously linked by a clinician to an indicated problem (36.53% of unlinked
      medications). Expert review of the combined knowledge base, including inferred
      and manually linked problem-medication pairs, found a sensitivity of 65.8% and a
      specificity of 97.9%. CONCLUSION: Crowdsourcing is an effective, inexpensive
      method for generating a knowledge base of problem-medication pairs that is
      automatically mapped to local terminologies, up-to-date, and reflective of local
      prescribing practices and trends.

PMID- 22582203
TI  - Impact of a web-based personally controlled health management system on influenza
      vaccination and health services utilization rates: a randomized controlled trial.
AB  - OBJECTIVE: To assess the impact of a web-based personally controlled health
      management system (PCHMS) on the uptake of seasonal influenza vaccine and primary
      care service utilization among university students and staff. MATERIALS AND
      METHODS: A PCHMS called Healthy.me was developed and evaluated in a 2010 CONSORT
      compliant two-group (6-month waitlist vs PCHMS) parallel randomized controlled
      trial (RCT) (allocation ratio 1:1). The PCHMS integrated an untethered personal
      health record with consumer care pathways, social forums, and messaging links
      with a health service provider. RESULTS: 742 university students and staff met
      inclusion criteria and were randomized to a 6-month waitlist (n=372) or the PCHMS
      (n=370). Amongst the 470 participants eligible for primary analysis, PCHMS users
      were 6.7% (95% CI: 1.46 to 12.30) more likely than the waitlist to receive an
      influenza vaccine (waitlist: 4.9% (12/246, 95% CI 2.8 to 8.3) vs PCHMS: 11.6%
      (26/224, 95% CI 8.0 to 16.5); chi(2)=7.1, p=0.008). PCHMS participants were also
      11.6% (95% CI 3.6 to 19.5) more likely to visit the health service provider
      (waitlist: 17.9% (44/246, 95% CI 13.6 to 23.2) vs PCHMS: 29.5% (66/224, 95% CI:
      23.9 to 35.7); chi(2)=8.8, p=0.003). A dose-response effect was detected, where
      greater use of the PCHMS was associated with higher rates of vaccination
      (p=0.001) and health service provider visits (p=0.003). DISCUSSION: PCHMS can
      significantly increase consumer participation in preventive health activities,
      such as influenza vaccination. CONCLUSIONS: Integrating a PCHMS into routine
      health service delivery systems appears to be an effective mechanism for
      enhancing consumer engagement in preventive health measures. TRIAL REGISTRATION:
      Australian New Zealand Clinical Trials Registry ACTRN12610000386033.
      http://www.anzctr.org.au/trial_view.aspx?id=335463.

PMID- 22582204
TI  - An improved model for predicting postoperative nausea and vomiting in ambulatory
      surgery patients using physician-modifiable risk factors.
AB  - OBJECTIVE: Postoperative nausea and vomiting (PONV) is a frequent complication in
      patients undergoing ambulatory surgery, with an incidence of 20%-65%. A
      predictive model can be utilized for decision support and feedback for
      practitioner practice improvement. The goal of this study was to develop a better
      model to predict the patient's risk for PONV by incorporating both non-modifiable
      patient characteristics and modifiable practitioner-specific anesthetic
      practices. MATERIALS AND METHODS: Data on 2505 ambulatory surgery cases were
      prospectively collected at an academic center. Sixteen patient-related, surgical,
      and anesthetic predictors were used to develop a logistic regression model. The
      experimental model (EM) was compared against the original Apfel model (OAM),
      refitted Apfel model (RAM), simplified Apfel risk score (SARS), and refitted
      Sinclair model (RSM) by examining the discriminating power calculated using area
      under the curve (AUC) and by examining calibration curves. RESULTS: The EM
      contained 11 input variables. The AUC was 0.738 for the EM, 0.620 for the OAM,
      0.629 for the RAM, 0.626 for the SARS, and 0.711 for the RSM. Pair-wise
      discrimination comparison of models showed statistically significant differences
      (p<0.05) in AUC between the EM and all other models, OAM and RSM, RAM and RSM,
      and SARS and RSM. DISCUSSION: All models except the OAM appeared to have good
      calibration for our institution's ambulatory surgery data. Ours is the first
      model to break down risk by anesthetic technique and incorporate risk reduction
      due to PONV prophylaxis. CONCLUSION: The EM showed statistically significant
      improved discrimination over existing models and good calibration. However, the
      EM should be validated at another institution.

PMID- 22582205
TI  - Machine learning-based coreference resolution of concepts in clinical documents.
AB  - OBJECTIVE: Coreference resolution of concepts, although a very active area in the
      natural language processing community, has not yet been widely applied to
      clinical documents. Accordingly, the 2011 i2b2 competition focusing on this area
      is a timely and useful challenge. The objective of this research was to collate
      coreferent chains of concepts from a corpus of clinical documents. These concepts
      are in the categories of person, problems, treatments, and tests. DESIGN: A
      machine learning approach based on graphical models was employed to cluster
      coreferent concepts. Features selected were divided into domain independent and
      domain specific sets. Training was done with the i2b2 provided training set of
      489 documents with 6949 chains. Testing was done on 322 documents. RESULTS: The
      learning engine, using the un-weighted average of three different measurement
      schemes, resulted in an F measure of 0.8423 where no domain specific features
      were included and 0.8483 where the feature set included both domain independent
      and domain specific features. CONCLUSION: Our machine learning approach is a
      promising solution for recognizing coreferent concepts, which in turn is useful
      for practical applications such as the assembly of problem and medication lists
      from clinical documents.

PMID- 22582206
TI  - An offline mobile nutrition monitoring intervention for varying-literacy patients
      receiving hemodialysis: a pilot study examining usage and usability.
AB  - OBJECTIVE: Design and evaluation of the dietary intake monitoring application
      (DIMA) to assist varying-literacy patients receiving hemodialysis to adhere to
      their prescribed dietary regimen. METHODS: An iterative, user-centered design
      process informed by Bandura's social cognitive theory was employed to design DIMA
      -a mobile application that utilizes touch-screen, visual interfaces; barcode
      scanning; and voice recording to assist varying-literacy patients receiving
      hemodialysis to self-monitor their diet. A pilot field study was conducted where
      18 patients receiving hemodialysis were recruited face-to-face from two dialysis
      facilities to use DIMA for 6 weeks. Subjects recorded their dietary intake using
      DIMA and met with research assistants three times each week. All interactions
      with DIMA were logged. Subjects' interdialytic weight gain was recorded
      throughout the study. At the end of the study, two face-to-face questionnaires
      were administered to assess usability and context of use. RESULTS: Subjects were
      able to use DIMA successfully--12 subjects used DIMA as much or more at the end
      of the study as they did at the beginning and reported that DIMA helped them
      change their diet. Subjects had difficulty using the barcode scanner. Viewing
      past meals was the most used of the reflection mechanisms in DIMA. CONCLUSION:
      Results suggest that while many design features were useful, some could be
      improved. In particular, future versions of DIMA will be on a smartphone using a
      camera for barcode scanning, integrate feedback and past meal reflection into the
      normal flow of the application, and support visual cues when selecting food
      items.

PMID- 22582207
TI  - Surveillance for adverse events following receipt of pandemic 2009 H1N1 vaccine
      in the Post-Licensure Rapid Immunization Safety Monitoring (PRISM) System, 2009
      2010.
AB  - The Post-Licensure Rapid Immunization Safety Monitoring (PRISM) system is a
      cohort-based active surveillance network initiated by the US Department of Health
      and Human Services to supplement preexisting and other vaccine safety monitoring
      systems in tracking the safety of monovalent pandemic 2009 H1N1 influenza vaccine
      in the United States during 2009-2010. PRISM investigators conducted
      retrospective analysis to determine whether 2009 H1N1 vaccination was associated
      with increased risk of any of 14 prespecified outcomes. Five health insurance and
      associated companies with 38 million members and 9 state/city immunization
      registries contributed records on more than 2.6 million doses of 2009 H1N1
      vaccine. Data on outcomes came from insurance claims. Complementary designs (self
      controlled risk interval, case-centered, and current-vs.-historical comparison)
      were used to optimize control for confounding and statistical power. The self
      controlled risk interval analysis of chart-confirmed Guillain-Barre syndrome
      found an elevated but not statistically significant incidence rate ratio
      following receipt of inactivated 2009 H1N1 vaccine (incidence rate ratio = 2.50,
      95% confidence interval: 0.42, 15.0) and no cases following live attenuated 2009
      H1N1 vaccine. The study did not control for infection prior to Guillain-Barre
      syndrome, which may have been a confounder. The risks of other health outcomes of
      interest were generally not significantly elevated after 2009 H1N1 vaccination.

PMID- 22582208
TI  - Invited commentary: Influenza vaccine and Guillain-Barre syndrome--is there a
      risk?
AB  - After a new reassortant swine influenza A H1N1 virus caused outbreaks in Mexico
      and the United States in 2009, a vaccine was prepared from this virus to immunize
      the entire US population. Surveillance for Guillain-Barre syndrome (GBS) after
      receipt of this vaccine was carried out in 3 populations: the Vaccine Safety
      Datalink Project, the 10 Centers for Disease Control and Prevention Emerging
      Infections Program sites, and a network of large insurance companies. These
      studies found a small increase of approximately 1 case of GBS per million
      vaccinees above the baseline rate, which is similar to that observed after
      administration of seasonal influenza vaccines over the past several years.
      Enhanced surveillance for GBS was conducted in 2009-2010 because of the
      experience in 1976 of 362 GBS cases' occurring during the 6 weeks after influenza
      vaccination of 45 million persons, an 8.8-fold increase over background rates.
      The 1976 mass immunization had been conducted to prevent an influenza epidemic
      from another swine influenza A H1N1 recombinant virus. It can be concluded from
      these recent studies that influenza vaccination overall is of public health
      benefit, helping to reduce mortality and prevent the thousands of deaths that
      occur from annual seasonal influenza outbreaks, despite the possibility of a
      small increased risk of GBS associated with influenza vaccines.

PMID- 22582209
TI  - Guillain-Barre syndrome during the 2009-2010 H1N1 influenza vaccination campaign:
      population-based surveillance among 45 million Americans.
AB  - Because of widespread distribution of the influenza A (H1N1) 2009 monovalent
      vaccine (pH1N1 vaccine) and the prior association between Guillain-Barre syndrome
      (GBS) and the 1976 H1N1 influenza vaccine, enhanced surveillance was implemented
      to estimate the magnitude of any increased GBS risk following administration of
      pH1N1 vaccine. The authors conducted active, population-based surveillance for
      incident cases of GBS among 45 million persons residing at 10 Emerging Infections
      Program sites during October 2009-May 2010; GBS was defined according to
      published criteria. The authors determined medical and vaccine history for GBS
      cases through medical record review and patient interviews. The authors used
      vaccine coverage data to estimate person-time exposed and unexposed to pH1N1
      vaccine and calculated age- and sex-adjusted rate ratios comparing GBS incidence
      in these groups, as well as age- and sex-adjusted numbers of excess GBS cases.
      The authors received 411 reports of confirmed or probable GBS. The rate of GBS
      immediately following pH1N1 vaccination was 57% higher than in person-time
      unexposed to vaccine (adjusted rate ratio = 1.57, 95% confidence interval: 1.02,
      2.21), corresponding to 0.74 excess GBS cases per million pH1N1 vaccine doses
      (95% confidence interval: 0.04, 1.56). This excess risk was much smaller than
      that observed during the 1976 vaccine campaign and was comparable to some
      previous seasonal influenza vaccine risk assessments.

PMID- 22582210
TI  - Risk of confirmed Guillain-Barre syndrome following receipt of monovalent
      inactivated influenza A (H1N1) and seasonal influenza vaccines in the Vaccine
      Safety Datalink Project, 2009-2010.
AB  - An increased risk of Guillain-Barre syndrome (GBS) following administration of
      the 1976 swine influenza vaccine led to a heightened focus on GBS when monovalent
      vaccines against a novel influenza A (H1N1) virus of swine origin were introduced
      in 2009. GBS cases following receipt of monovalent inactivated (MIV) and seasonal
      trivalent inactivated (TIV) influenza vaccines in the Vaccine Safety Datalink
      Project in 2009-2010 were identified in electronic data and confirmed by medical
      record review. Within 1-42 days following vaccination, 9 cases were confirmed in
      MIV recipients (1.48 million doses), and 8 cases were confirmed in TIV-only
      recipients who did not also receive MIV during 2009-2010 (1.72 million doses).
      Five cases following MIV and 1 case following TIV-only had an antecedent
      respiratory infection, a known GBS risk factor; furthermore, unlike TIV, MIV
      administration was concurrent with heightened influenza activity. In a self
      controlled risk interval analysis comparing GBS onset within 1-42 days following
      MIV with GBS onset 43-127 days following MIV, the risk difference was 5.0 cases
      per million doses (95% confidence interval: 0.5, 9.5). No statistically
      significant increased GBS risk was found within 1-42 days following TIV-only
      vaccination versus 43-84 days following vaccination (risk difference = 1.1 cases
      per million doses, 95% confidence interval: -3.1, 5.4). Further evaluation to
      assess GBS risk following both vaccination and respiratory infection is
      warranted.

PMID- 22582211
TI  - Noninvasive evaluation of skeletal muscle mitochondrial capacity with near
      infrared spectroscopy: correcting for blood volume changes.
AB  - Near-infrared spectroscopy (NIRS) is a well-known method used to measure muscle
      oxygenation and hemodynamics in vivo. The application of arterial occlusions
      allows for the assessment of muscle oxygen consumption (mVo(2)) using NIRS. The
      aim of this study was to measure skeletal muscle mitochondrial capacity using
      blood volume-corrected NIRS signals that represent oxygenated
      hemoglobin/myoglobin (O(2)Hb) and deoxygenated hemoglobin/myoglobin (HHb). We
      also assessed the reliability and reproducibility of NIRS measurements of resting
      oxygen consumption and mitochondrial capacity. Twenty-four subjects, including
      four with chronic spinal cord injury, were tested using either the vastus
      lateralis or gastrocnemius muscles. Ten healthy, able-bodied subjects were tested
      on two occasions within a period of 7 days to assess the reliability and
      reproducibility. NIRS signals were corrected for blood volume changes using three
      different methods. Resting oxygen consumption had a mean coefficient of variation
      (CV) of 2.4% (range 1-32%). The recovery of oxygen consumption (mVo(2)) after
      electrical stimulation at 4 Hz was fit to an exponential curve, which represents
      mitochondrial capacity. The time constant for the recovery of mVo(2) was
      reproducible with a mean CV of 10% (range 1-22%) only when correcting for blood
      volume changes. We also examined the effects of adipose tissue thickness on
      measurements of mVo(2). We found the mVo(2) measurements using absolute units to
      be influenced by adipose tissue thickness (ATT), and this relationship was
      removed when an ischemic calibration was performed, supporting its use to compare
      mVo(2) between individuals of varying ATT. In conclusion, in vivo oxidative
      capacity can be assessed using blood volume-corrected NIRS signals with a high
      degree of reliability and reproducibility.

PMID- 22582212
TI  - Vectorcardiography analysis of the repolarization response to pharmacologically
      induced autonomic nervous system modulation in healthy subjects.
AB  - Autonomic nervous system activity is essential for regulation of ventricular
      repolarization (VR) and plays an important role in several arrhythmogenic
      conditions. This study in 31 healthy adult subjects (16 men, 15 women) evaluated
      the VR response to pharmacologically modulated autonomic nervous system activity
      applying vectorcardiography (VCG) analysis. During continuous VCG recording, 0.01
      0.1 MUg.kg(-1).min(-1) isoprenaline (Iso) was infused at an increasing flow rate
      until three targeted heart rates (HR) were reached. After Iso washout, one
      intravenous bolus of 0.04 mg/kg atropine was given followed by an intravenous
      bolus of 0.2 mg/kg propranolol. A 5-min steady-state VCG recording was analyzed
      for each of the seven phases (including baseline 1 and 2). Furthermore, during
      the first 4 min following atropine, six periods of 10-s VCG were selected for
      subanalysis to evaluate the time course of change. The analysis included QRS, QT,
      and T-peak to T-end intervals, measures of the QRS and T vectors and their
      relation, as well as T-loop morphology parameters. By increasing HR, Iso infusion
      decreased HR dependent parameters reflecting total heterogeneity of VR (T area)
      and action potential morphology (ventricular gradient). In contrast, Iso
      prolonged QT HR corrected according to Bazett and increased the T-peak to T-end
      to-QT ratio to levels observed in arrhythmogenic conditions. HR acceleration
      after atropine was accompanied by a transient paradoxical QT prolongation and
      delayed HR adaptation of T area and ventricular gradient. In addition to the
      expected HR adaptation, the VR response to beta-adrenoceptor stimulation with Iso
      and to muscarinic receptor blockade with atropine thus included alterations
      previously observed in congenital and acquired long QT syndromes, demonstrating
      substantial overlap between physiological and pathophysiological
      electrophysiology.

PMID- 22582213
TI  - No change in myonuclear number during muscle unloading and reloading.
AB  - Muscle fibers are the cells in the body with the largest volume, and they have
      multiple nuclei serving different domains of cytoplasm. A large body of previous
      literature has suggested that atrophy induced by hindlimb suspension leads to a
      loss of "excessive" myonuclei by apoptosis. We demonstrate here that atrophy
      induced by hindlimb suspension does not lead to loss of myonuclei despite a
      strong increase in apoptotic activity of other types of nuclei within the muscle
      tissue. Thus hindlimb suspension turns out to be similar to other atrophy models
      such as denervation, nerve impulse block, and antagonist ablation. We discuss how
      the different outcome of various studies can be attributed to difficulties in
      separating myonuclei from other nuclei, and to systematic differences in passive
      properties between normal and unloaded muscles. During reload, after hindlimb
      suspension, a radial regrowth is observed, which has been believed to be
      accompanied by recruitment of new myonuclei from satellite cells. The lack of
      nuclear loss during unloading, however, puts these findings into question. We
      observed that reload led to an increase in cross sectional area of 59%, and fiber
      size was completely restored to the presuspension levels. Despite this notable
      growth there was no increase in the number of myonuclei. Thus radial regrowth
      seems to differ from de novo hypertrophy in that nuclei are only added during the
      latter. We speculate that the number of myonuclei might reflect the largest size
      the muscle fibers have had in its previous history.

PMID- 22582214
TI  - Short-term exercise reduces markers of hepatocyte apoptosis in nonalcoholic fatty
      liver disease.
AB  - Increased hepatocyte apoptosis is a hallmark of nonalcoholic fatty liver disease
      (NAFLD) and contributes to the profibrogenic state responsible for the
      progression to nonalcoholic steatohepatitis (NASH). Strategies aimed at reducing
      apoptosis may result in better outcomes for individuals with NAFLD. We therefore
      examined the effect of a short-term exercise program on markers of apoptosis
      plasma cytokeratin 18 (CK18) fragments, alanine aminotransferase (ALT), aspartate
      aminotransferase (AST), soluble Fas (sFas), and sFas ligand (sFasL)-in 13 obese
      individuals with NAFLD [body mass index 35.2 +/- 1.2 kg/m(2), >5% intrahepatic
      lipid (IHL) assessed by (1)H-MR spectroscopy]. Exercise consisted of treadmill
      walking for 60 min/day on 7 consecutive days at ~85% of maximal heart rate.
      Additionally, subjects underwent an oral glucose tolerance test and a maximal
      oxygen consumption (Vo(2max)) test before and after the exercise intervention.
      The Matsuda index was used to assess insulin sensitivity. We observed significant
      decreases in CK18 fragments (558.4 +/- 106.8 vs. 323.4 +/- 72.5 U/l, P < 0.01)
      and ALT (30.2 +/- 5.1 vs. 24.3 +/- 4.8 U/l, P < 0.05), and an increase in whole
      body fat oxidation (49.3 +/- 6.1 vs. 69.4 +/- 7.1 mg/min, P < 0.05), while
      decreases in circulating sFasL approached statistical significance (66.5 +/- 6.0
      vs. 63.0 +/- 5.7 pg/ml, P = 0.06), as did the relationship between percent change
      in circulating CK18 fragments and ALT (r = 0.55, P = 0.05). We also observed a
      significant correlation between changes in fat oxidation and circulating sFasL
      (rho = -0.65, P < 0.05). There was no change in IHL following the intervention
      (18.2 +/- 2.5 vs. 17.5 +/- 2.1%, NS). We conclude that short-term exercise
      reduces a circulatory marker of hepatocyte apoptosis in obese individuals with
      NAFLD and propose that changes in the proapoptotic environment may be mediated
      through improved insulin sensitivity and increased oxidative capacity.

PMID- 22582215
TI  - Involvement of enhanced cardiac sympathetic afferent reflex in sympathetic
      activation in early stage of diabetes.
AB  - Cardiac sympathetic afferent reflex (CSAR) is involved in sympathetic activation.
      The present study was designed to investigate the contribution of enhanced CSAR
      to sympathetic activation in the early stage of diabetes and the involvement of
      AT(1) receptors in the paraventricular nucleus (PVN). Diabetes was induced by a
      single intravenous injection of streptozotocin in rats. Acute experiments were
      carried out under anesthesia after 3 wk. The CSAR was evaluated by the responses
      of renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) to
      epicardial application of capsaicin or bradykinin. Sympathetic activity and CSAR
      were enhanced in diabetic rats. Plasma norepinephrine and angiotensin II were
      increased, but the transient receptor potential vanilloid 1 (TRPV1) in the left
      ventricle wall was not significantly increased in diabetic rats. Pericardial
      injection of resiniferatoxin to desensitize cardiac afferents or PVN
      microinjection of lidocaine attenuated the CSAR and decreased the RSNA and MAP in
      diabetic rats. The AT(1) receptor expression in the PVN increased in diabetic
      rats. Angiotensin II in the PVN caused greater increases in the RSNA and MAP and
      enhancement in the CSAR in diabetic rats, which were abolished by the losartan
      pretreatment. Losartan decreased the RSNA and MAP and attenuated the CSAR in
      diabetic rats but not in control rats. These results indicate that the CSAR is
      enhanced in the early stage of diabetic rats, which contributes to the
      sympathetic activation. AT(1) receptors in the PVN are involved in the enhanced
      CSAR in diabetic rats.

PMID- 22582216
TI  - What can imaging tell us about physiology? Lung growth and regional mechanical
      strain.
AB  - The interplay of mechanical forces transduces diverse physico-biochemical
      processes to influence lung morphogenesis, growth, maturation, remodeling and
      repair. Because tissue stress is difficult to measure in vivo, mechano-sensitive
      responses are commonly inferred from global changes in lung volume, shape, or
      compliance and correlated with structural changes in tissue blocks sampled from
      postmortem-fixed lungs. Recent advances in noninvasive volumetric imaging
      technology, nonrigid image registration, and deformation analysis provide
      valuable tools for the quantitative analysis of in vivo regional anatomy and air
      and tissue-blood distributions and when combined with transpulmonary pressure
      measurements, allow characterization of regional mechanical function, e.g.,
      displacement, strain, shear, within and among intact lobes, as well as between
      the lung and the components of its container-rib cage, diaphragm, and mediastinum
      thereby yielding new insights into the inter-related metrics of mechanical stress
      strain and growth/remodeling. Here, we review the state-of-the-art imaging
      applications for mapping asymmetric heterogeneous physical interactions within
      the thorax and how these interactions permit as well as constrain lung growth,
      remodeling, and compensation during development and following pneumonectomy to
      illustrate how advanced imaging could facilitate the understanding of physiology
      and pathophysiology. Functional imaging promises to facilitate the formulation of
      realistic computational models of lung growth that integrate mechano-sensitive
      events over multiple spatial and temporal scales to accurately describe in vivo
      physiology and pathophysiology. Improved computational models in turn could
      enhance our ability to predict regional as well as global responses to
      experimental and therapeutic interventions.

PMID- 22582218
TI  - A comparison of two Hill-type skeletal muscle models on the construction of
      medial gastrocnemius length-tension curves in humans in vivo.
AB  - Human length-tension curves are traditionally constructed using a model that
      assumes passive tension does not change during contraction (model A) even though
      the animal literature suggests that passive tension can decrease (model B). The
      study's aims were threefold: 1) measure differences in human medial gastrocnemius
      length-tension curves using model A vs. model B, 2) test the reliability of
      ultrasound constructed length-tension curves, and 3) test the robustness of
      fascicle length-generated length-tension curves to variations between the angle
      and fascicle length relationship. An isokinetic dynamometer manipulated and
      measured ankle angle while ultrasound was used to measure medial gastrocnemius
      fascicle length. Supramaximal tibial nerve stimulation was used to evoke resting
      muscle twitches. Length-tension curves were constructed using model A {angle
      torque [A-T((A))], length-torque [L-T((A))]} or model B {length-torque [L
      T((B))]} in three conditions: baseline, heel-lift (where the muscle was shortened
      at each angle), and baseline repeated 2 h later (+2 h). Length-tension curves
      constructed from model B differed from those produced via model A, indicated by a
      significant increase in maximum torque (~23%) when using L-T((B)) vs. L-T((A)).
      No parameter measured was different between baseline and +2 h for any method,
      indicating good reliability when using ultrasound. Length-tension curves were
      unaffected by the heel-lift condition when using L-T((A)) or L-T((B)) but were
      affected when using A-T((A)). Since the muscle model used significantly alters
      human length-tension curves, and given animal data indicate model B to be more
      accurate when passive tension is present, we recommend that model B should be
      used when constructing medial gastrocnemius length-tension curves in humans in
      vivo.

PMID- 22582219
TI  - The need for speed: central command commanding vasodilation in human skeletal
      muscle?

PMID- 22582217
TI  - Imaging for lung physiology: what do we wish we could measure?
AB  - The role of imaging as a tool for investigating lung physiology is growing at an
      accelerating pace. Looking forward, we wished to identify unresolved issues in
      lung physiology that might realistically be addressed by imaging methods in
      development or imaging approaches that could be considered. The role of imaging
      is framed in terms of the importance of good spatial and temporal resolution and
      the types of questions that could be addressed as these technical capabilities
      improve. Recognizing that physiology is fundamentally a quantitative science, a
      recurring emphasis is on the need for imaging methods that provide reliable
      measurements of specific physiological parameters. The topics included
      necessarily reflect our perspective on what are interesting questions and are not
      meant to be a comprehensive review. Nevertheless, we hope that this essay will be
      a spur to physiologists to think about how imaging could usefully be applied in
      their research and to physical scientists developing new imaging methods to
      attack challenging questions imaging could potentially answer.

PMID- 22582220
TI  - Comparison of relative distribution of ketamine and norketamine in decomposed
      skeletal tissues following single and repeated exposures.
AB  - Bone was analyzed for ketamine and norketamine to examine whether different
      patterns of drug exposure could be discriminated. Rats received
      (intraperitoneally) one 75 mg/kg dose (Acute-1 and Acute-2 groups), three 25
      mg/kg doses 1 hour apart (Repeated group), or nine single daily ketamine doses of
      75 mg/kg followed by a 24-h washout period (Chronic group). Following euthanasia,
      all animals decomposed to skeleton outdoors. Ground samples of recovered bone
      underwent methanolic extraction and analysis by gas chromatography-mass
      spectrometry after solid-phase extraction. Drug levels (mass normalized response
      ratios) were compared across bone types and exposure pattern. Bone type
      significantly influenced drug level for the Acute-1 and Repeated dose groups, and
      the drug/metabolite level ratio (DMLR) for the Acute-1 group. Mean ketamine and
      norketamine level and DMLR varied by up to 8-fold, 7-fold and 3-fold,
      respectively, in the Acute-1 group, and by up to 24-fold, 5-fold and 10-fold,
      respectively, in the Repeated group. Drug level and DMLR differed significantly
      between the Acute-1 and Repeated groups for most bone types. In the Chronic
      group, only 1/16 and 4/16 samples were positive for ketamine and norketamine,
      respectively. All Acute-2 samples were positive for ketamine and norketamine. The
      Acute-2 and Chronic groups differed significantly in ketamine and norketamine
      levels, and DMLR.

PMID- 22582221
TI  - Distribution of methylone in four postmortem cases.
AB  - Drugs derived from amphetamine, methamphetamine and their methylenedioxy-
      analogues, although being sold as plant food or bath salts, are being used as
      legal alternatives to scheduled amphetamine stimulants. These products often
      contain methylone, mephedrone and methylenedioxypyrovalerone (MDPV)--three
      amphetamine derivatives shown to have strong pharmacological effects. Four
      postmortem cases were analyzed for methylone, mephedrone and MDPV, with drug
      levels quantitated in multiple biological matrices. All four cases had detectable
      levels of methylone, with heart blood concentrations of 0.740, 0.118, 0.060 and
      1.12 mg/L. Analysis of several tissue samples shows that methylone does not
      sequester in a particular tissue type after death. The average liver-to-blood
      ratio was 2.68. Two cases also had MDPV present, but insufficient data were
      collected to formulate a hypothesis on postmortem sequestration or
      redistribution. Two different extraction methods, as well as analysis of
      derivatized and underivatized methylone, show that the drug is suitable for
      analysis in either method. The cases are believed to show one instance of chronic
      methylone use, with a urine concentration of 38 mg/L.

PMID- 22582222
TI  - Suture-only fixation technique leads to a higher degree of extrusion than bony
      fixation in meniscal allograft transplantation.
AB  - BACKGROUND: Most of the published series of transplanted menisci have
      consistently shown some degree of allograft extrusion. The speculation is that
      this meniscal extrusion may be caused by the soft tissue technique used to fix
      the allograft. HYPOTHESIS: The percentage of extruded meniscal graft would be
      higher if the allograft were only fixed with sutures rather than with associated
      bony fixation. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: We
      performed a prospective series of 88 meniscal allograft transplantations. Thirty
      three of the grafts were fixed with the suture-only technique (group A). The
      remaining 55 cases were performed with the bone plug method (group B). All
      patients were studied with magnetic resonance imaging (MRI) at a minimum 3 years'
      follow-up to determine the degree of meniscal extrusion. The time between surgery
      and MRI evaluation was 40 months (range, 36-48 months) in both groups. Meniscal
      extrusion was measured on coronal MRI. The percentage of the meniscal body width
      that was extruded was calculated. The average percentage of extrusion for each
      group was compared. The Lysholm score was analyzed in relation to the fixation
      method and degree of meniscal extrusion. Tears of the allograft that required
      surgical intervention were also reported. RESULTS: The average percentage of
      meniscal tissue extruded in group A was 36.3% +/- 13.7% without differences
      between the medial (35.9% +/- 18.1%) and lateral (38.3% +/- 14.4%) compartments
      (P = .84). Group B had a mean 28.13% +/- 12.2% of the meniscal body extruded
      without differences between the medial (25.8% +/- 16.2%) and lateral (30.14% +/-
      13.5%) compartments. A higher percentage of extruded meniscal tissue was found in
      group A than in group B (P < .001). No association between the degree of meniscal
      extrusion and the functional score was observed (P = .4). Graft tears were
      observed in 21.4% of the cases in group A and in 7.3% of the cases in group B (P
      = .09). CONCLUSION: A meniscal allograft fixed with the suture-only technique
      showed a significantly higher degree of extruded meniscal body than that fixed
      with the bony fixation method, with no influence on the functional outcome. There
      was also a considerably higher rate of graft tears observed in those menisci
      fixed only with sutures, although this difference was not statistically
      significant with the numbers available.

PMID- 22582223
TI  - Catastrophic injuries in pole vaulters: a prospective 9-year follow-up study.
AB  - BACKGROUND: A prior review of catastrophic pole vaulting injuries from 1982
      through 1998 revealed an average of 2.0 injuries per year, with 69% (1.38 per
      year) of the injuries secondary to athletes landing off the sides or back of the
      landing pad and 25% (0.5 per year) from athletes landing in the vault box. In
      2003, several rule changes for the sport of pole vaulting were mandated,
      including enlarging the minimum dimensions of the landing pad.
      HYPOTHESIS/PURPOSE: Our goals were to (1) identify the post-2003 rule change
      incidence and profile of catastrophic pole vaulting injuries through 2011 and
      compare them, where possible, with the prior incidence and profile and (2)
      determine, via a questionnaire, the frequency with which pole vaulters land in
      the vault box. We hypothesized that the new, larger landing pads would reduce the
      number of catastrophic injuries. STUDY DESIGN: Descriptive epidemiology study.
      METHODS: We prospectively reviewed all catastrophic pole vaulting injuries (ie,
      brain hemorrhage; skull, spine, or pelvic fracture; substantial pulmonary or
      intra-abdominal injury) in the United States from 2003 through 2011, surveyed
      3335 pole vaulters to determine the frequency of landing in the vault box, and
      compared results with those in the literature. RESULTS: From 2003 to 2011, 19
      catastrophic injuries occurred (average of 2.1 per year), with the majority (n =
      14, 74%, 1.55 per year) landing in or around the vault box. Four (21%, 0.44 per
      year) injuries occurred when an athlete landed off the sides or back of the
      landing pad and 1 (5%) when the pole broke. There were 11 (58%) major head
      injuries (1 fatality), 4 (21%) spine fractures (1 with paraplegia), 2 (11%)
      pelvic fractures (both with intra-abdominal injuries), 1 (5%) brain stem injury
      (fatal), and 1 (5%) thoracic injury (rib fractures and pneumothorax). The annual
      fatality rate fell from 1.0 in the prior study to 0.22 in the current study.
      According to the pole vaulters survey, during their careers, 77.12% (n = 2572)
      landed in the vault box 1 to 3 times, 15.92% (n = 531) never landed in the vault
      box, 6.12% (n = 204) landed in the vault box 4 to 6 times, and 0.84% (n = 28)
      landed in the vault box 7 or more times. CONCLUSION: The 2003 rule changes have
      markedly reduced the number of catastrophic injuries, especially fatalities, from
      pole vaulters missing the back or sides of the landing pads; however, the average
      annual rate of catastrophic injuries from pole vaulters landing in the vault box
      has more than tripled over the past decade and remains a major problem.

PMID- 22582224
TI  - Risk factors for medial meniscus posterior root tear.
AB  - BACKGROUND: Medial meniscus posterior root tears (MMPRT) have a different
      clinical effect from other types of meniscal tears. These tears are very common
      among Asian people and may be related to the frequent use of postures such as the
      lotus position or squatting. PURPOSE: The present study was designed to identify
      the risk factors for MMPRT among an Asian sample. STUDY DESIGN: Cohort study;
      Level of evidence, 3. METHODS: An observational study was performed of 476
      consecutive patients undergoing an arthroscopic procedure on their medial
      meniscus from January 2010 to December 2010. One hundred four patients had MMPRT
      (group 1), and the other patients had other types of medial meniscal tears (group
      2). Demographic characteristics (age, sex, body mass index [BMI]), radiographic
      features (mechanical axis angle, tibia vara angle, tibial slope angle, Kellgren
      Lawrence grade [KLG]), and environmental factors (occupation, trauma history,
      sports activity level, table use or not, bed use or not-variables that are
      representative of the oriental lifestyle of lotus position and squatting) were
      surveyed. We assessed the relation of these risk factors to the type of meniscal
      tear (group 1 or 2). RESULTS: In group 1, there were 7 male and 97 female
      patients, with an average age of 58.2 years (range, 39-78 years) and BMI of 26.7
      +/- 3.4 kg/m2. In group 2, there were 136 male and 236 female patients (P < .01
      compared with group 1), with an average age of 54.3 years (range, 17-77 years; P
      < .01) and a BMI of 24.9 +/- 3.1 kg/m2 (P < .01). With regard to radiographic
      features, the mechanical axis angle demonstrated a significantly increased varus
      alignment in group 1 (4.5 degrees  +/- 3.4 degrees ) compared with group 2 (2.4
      degrees  +/- 2.7 degrees ; P < .01), and the KLG was 1.4 +/- 0.8 in group 1 and
      0.9 +/- 0.6 in group 2 (P < .01). Environmental factors showed no differences in
      occupation, table use or not, and bed use or not, except sports activity level.
      There were 41 patients (42.7%) in group 1 and 77 patients (20.6%) in group 2 who
      did not participate in any recreational activity (P < .01). Multiple logistic
      regression analysis showed that female sex was associated with a 5.9-fold
      increase in risk (95% confidence interval [CI], 2.138-16.575), a varus mechanical
      axis angle with a 3.3-fold increase (95% CI, 1.492-7.153), a BMI more than 30
      kg/m2 with a 4.9-fold increase (95% CI, 1.160-20.955), and lower sports activity
      level with a 2.7-fold increase (95% CI, 1.011-7.163) for MMPRT. CONCLUSION:
      Persons with MMPRT had significantly increased age, female sex predominance,
      higher BMI, increased KLG, greater varus mechanical axis angle, and lower sports
      activity level compared with persons with other types of meniscal tear. After
      adjusting for other factors, sex, BMI, mechanical axis angle, and lower sports
      activity level remained strong determinants of MMPRT. Interestingly, oriental
      postural positions including the lotus position and squatting showed no
      contribution to increased risk of MMPRT. This suggests that intrinsic risk
      factors (similar to those that predispose to osteoarthritis) predispose to MMPRT.

PMID- 22582225
TI  - Ulnar collateral ligament reconstruction with gracilis tendon in athletes with
      intraligamentous bony excision: technique and results.
AB  - BACKGROUND: Ulnar collateral ligament (UCL) reconstruction is frequently
      performed in throwing athletes, but outcomes of UCL reconstruction requiring
      excision of bone, either within the substance of or replacing the UCL, have not
      been studied. HYPOTHESIS: Clinical outcome for throwing athletes after UCL
      reconstruction with gracilis tendon will be less favorable for patients requiring
      concurrent excision of bone from within the substance of the UCL than for
      patients with no bone excision within, or replacing, the ligamentous anatomy.
      STUDY DESIGN: Cohort Study; Level of evidence, 3. METHODS: One hundred twenty
      pitchers of competitive levels between high school and major league who underwent
      UCL reconstruction using contralateral gracilis autografts completed a phone
      survey, and their medical charts were reviewed. Follow-up was a minimum of 2
      years. Among the 120 patients, 42 (35%) had bone within, or replacing, the
      substance of the native UCL (bony group), and 78 (65%) had no bony abnormalities
      (nonbony group). The latter group of 78 underwent UCL reconstruction using
      gracilis tendon graft due to the absence of a palmaris longus tendon. Clinical
      outcomes were compared between the 2 study groups using t tests and chi2
      analyses. RESULTS: There were no statistical differences regarding time to return
      to throwing, time to return to competition, postoperative complications, or need
      for additional surgeries. The percentage of patients who returned to the same or
      higher level was higher in the nonbony group (91%) than in the bony group (81%),
      but this trend was not statistically significant (P = .083), likely due to a
      relatively small sample size. Changes in self-reported pitch control were
      different (P = .029) between the 2 groups, with a greater percentage of pitchers
      experiencing decreased control in the bony group. CONCLUSION: The presence of
      bone concomitant with UCL damage can lead to pitch control problems after UCL
      reconstruction and may also decrease the chance of return to play.

PMID- 22582226
TI  - Shortcuts in arthroscopic knot tying: do they affect knot and loop security?
AB  - BACKGROUND: Shortcuts for throwing 3 alternating reversed half-hitches on
      alternating posts (RHAPs), in which the post is switched by alternating strand
      tension to "flip" the knot, have been advocated but never validated in a
      biomechanical study. HYPOTHESIS: Shortcut tying techniques will affect knot
      security or loop security. STUDY DESIGN: Controlled laboratory study. METHODS: A
      single surgeon tied 90 knots using No. 2 FiberWire through an arthroscopic
      cannula. Half had a static "surgeon's base," and half had a Tennessee slider
      base. Three techniques were used to create 3 RHAPs: (1) rethreading, (2) knot
      "flipping" where half-hitches were tensioned by past-pointing, and (3) knot
      "flipping" where half-hitches were tensioned by alternating past-pointing and
      over-pointing. Each knot was subjected to a preload of 5 N, followed by 1000
      cycles of 5 N to 45 N at 1 Hz, and a single load to failure. RESULTS: When
      compared with Tennessee knots, surgeon's knots had a lower incidence of knot
      slippage and catastrophic failure as well as higher loads to clinical and
      ultimate failure. Shortcut techniques did not affect the properties of surgeon's
      knots. However, when used to secure Tennessee knots, past-pointing decreased load
      to clinical failure and ultimate load to failure. Over-pointing increased the
      incidence of knot slippage and catastrophic failure and decreased load to
      clinical failure and ultimate load to failure. Loop security was marginally
      increased by both past-pointing and over-pointing. CONCLUSION: When all tying
      techniques are considered, surgeon's knots outperform Tennessee sliding knots.
      Shortcut techniques do not alter the properties of surgeon's knots. However, when
      used to secure Tennessee sliding knots, shortcuts lead to unacceptably high rates
      of knot slippage and catastrophic failure as well as decreased knot security.
      CLINICAL RELEVANCE: The outcomes of arthroscopic rotator cuff or labral repairs
      can be compromised when using shortcut tying methods to secure sliding Tennessee
      knots.

PMID- 22582227
TI  - The Western Ontario rotator cuff index in rotator cuff disease patients: a
      comprehensive reliability and responsiveness validation study.
AB  - BACKGROUND: The Western Ontario rotator cuff index (WORC) is an increasingly
      applied condition-specific outcome measure for rotator cuff (RC) conditions.
      However, in most WORC validation studies, only a limited number of psychometric
      properties are studied in indistinct patient groups. PURPOSE: To assess
      psychometric properties of the WORC according to the Scientific Advisory
      Committee quality criteria for health questionnaires in 3 patient groups with
      distinct RC conditions. STUDY DESIGN: Cohort study (diagnosis); Level of
      evidence, 2. METHODS: The WORC (range, 0-100; 21 items, 5 domains) was
      administered twice (T1, T2) in 92 patients (35 RC tears, 35 calcific tendinitis,
      22 impingement). Additionally, the Constant score (CS) and the Disabilities of
      the Arm, Shoulder and Hand score (DASH) were recorded. Calcific tendinitis
      patients were reassessed 6 weeks after treatment with needling and lavage or a
      subacromial injection with corticosteroids (T3). We assessed floor and ceiling
      effects, internal consistency, test-retest reliability, precision, construct
      validity, minimally detectable change, and responsiveness in the diagnostic
      subgroups and the total group. RESULTS: Mean age was 55.0 +/- 8.7 years, and 49
      of 92 (53%) patients were female. Mean baseline WORC was 46.8 +/- 20.4, CS was
      63.9 +/- 15.4, and DASH was 40.9 +/- 18.6. Significant differences were found for
      the CS and DASH between RC tear patients (severe symptoms) and the other
      patients, but not for the WORC. There were no floor and ceiling effects. Internal
      consistency was high: the Cronbach alpha coefficient was .95. The intraclass
      correlation coefficient of .89 and standard error of measurement of 6.9 indicated
      high reproducibility. Pearson correlations of the WORC with the CS and DASH were
      .56 and -.65, respectively (both P < .001). At T3, total WORC improved
      significantly (mean change, 18.8; 95% confidence interval, 11.3-26.2).
      Correlations of the WORC change scores with CS and DASH changes were .61 and 
      .84, respectively (both P < .001). Effect size was 0.96, with a standardized
      response mean of 0.91, indicating good responsiveness. CONCLUSION: Applied to a
      variety of RC patients, the WORC had high internal consistency, moderate to good
      construct validity, high test-retest reliability, and good responsiveness. These
      findings support the use of the WORC as a condition-specific self-reported
      outcome measure in RC patients, but its validity in patients with severe symptoms
      needs further investigation.

PMID- 22582228
TI  - Restoration of anterior glenoid bone defects in posttraumatic recurrent anterior
      shoulder instability using the J-bone graft shows anatomic graft remodeling.
AB  - BACKGROUND: The J-bone graft technique has previously been reported for anatomic
      restoration of the bony glenoid surface in cases of posttraumatic recurrent
      anterior shoulder instability with significant glenoid bone loss. PURPOSE: To
      analyze the physiological remodeling process of the J-bone graft over time. STUDY
      DESIGN: Case series; Level of evidence, 4. METHODS: Thirty-one consecutive
      patients treated with anatomic glenoid restoration surgery using the J-bone graft
      for posttraumatic recurrent anterior shoulder instability with a significant bony
      glenoid defect were included in this study. Twenty patients received 3
      dimensional computed tomography scans of the affected shoulder preoperatively,
      postoperatively, and at 1-year follow-up. On "en face" views of the glenoid, the
      change over time of the glenoid diameter, glenoid area, and glenoid defect size
      in relation to a best-fit circle indicating 100% was measured. RESULTS: The
      average glenoid diameter increased from 81.0% preoperatively to 110.4%
      postoperatively (P < .001). At 1-year follow-up, the diameter had decreased
      significantly to 100.6% (P < .001), which is concordant to a theoretical perfect
      glenoid diameter of 100% (P = .73). The average glenoid surface area increased
      from 80.8% preoperatively to 110.0% postoperatively (P < .001). At 1-year follow
      up, a decrease to 102.2% (P < .005) was measured, which again is close to a
      theoretical perfect glenoid surface area of 100% (P = .15). By applying the J
      bone graft, the average missing surface area of the glenoid was reduced from
      19.2% preoperatively to 3.9% postoperatively (P < .001). At 1-year follow-up, an
      average of 3.6% was calculated, indicating no statistically significant change
      over time (P = .90). CONCLUSION: Anatomic glenoid reconstructive surgery using
      the J-bone graft technique benefits from a physiological remodeling process,
      molding the bone graft closely into the original shape of an uninjured anterior
      glenoid rim. While parts of the graft lying inside the projected former surface
      area of the glenoid are preserved, the parts lying outside are resorbed over
      time, suggestive of strain-adapted graft remodeling.

PMID- 22582229
TI  - Tackling human fungal infections.

PMID- 22582234
TI  - Space science. Europe picks Jupiter probe; runners-up vow to press on.

PMID- 22582235
TI  - Lab exposure. Death of California researcher spurs investigation.

PMID- 22582236
TI  - Astronomy. Venus's rare sun crossing may aid search for exoplanets.

PMID- 22582237
TI  - Condensed-matter physics. Reprise of first experiment casts doubt on supersolid
      helium.

PMID- 22582238
TI  - Paleobotany. Primeval land rises from the ashes.

PMID- 22582239
TI  - Invasive species. Researchers set course to blockade ballast invaders.

PMID- 22582240
TI  - Invasive species. A foul problem.

PMID- 22582241
TI  - Chagas disease. With novel paint, chemist aims to vanquish the vinchuca.

PMID- 22582242
TI  - Conservation concerns in the deep.

PMID- 22582244
TI  - Presumed guilt in the anthrax case.

PMID- 22582247
TI  - Research priorities. ELSI 2.0 for genomics and society.

PMID- 22582248
TI  - Cell biology. FGF21 takes a fat bite.

PMID- 22582249
TI  - Geophysics. Understanding earthquakes.

PMID- 22582250
TI  - Structural biology. PARP-1 activation--bringing the pieces together.

PMID- 22582251
TI  - Physics. Intertwining electron tunneling with light.

PMID- 22582252
TI  - Molecular biology. RNA plays meiotic matchmaker.

PMID- 22582253
TI  - Dawn at Vesta: testing the protoplanetary paradigm.
AB  - The Dawn spacecraft targeted 4 Vesta, believed to be a remnant intact protoplanet
      from the earliest epoch of solar system formation, based on analyses of howardite
      eucrite-diogenite (HED) meteorites that indicate a differentiated parent body.
      Dawn observations reveal a giant basin at Vesta's south pole, whose excavation
      was sufficient to produce Vesta-family asteroids (Vestoids) and HED meteorites.
      The spatially resolved mineralogy of the surface reflects the composition of the
      HED meteorites, confirming the formation of Vesta's crust by melting of a
      chondritic parent body. Vesta's mass, volume, and gravitational field are
      consistent with a core having an average radius of 107 to 113 kilometers,
      indicating sufficient internal melting to segregate iron. Dawn's results confirm
      predictions that Vesta differentiated and support its identification as the
      parent body of the HEDs.

PMID- 22582254
TI  - Vesta's shape and morphology.
AB  - Vesta's surface is characterized by abundant impact craters, some with preserved
      ejecta blankets, large troughs extending around the equatorial region, enigmatic
      dark material, and widespread mass wasting, but as yet an absence of volcanic
      features. Abundant steep slopes indicate that impact-generated surface regolith
      is underlain by bedrock. Dawn observations confirm the large impact basin
      (Rheasilvia) at Vesta's south pole and reveal evidence for an earlier, underlying
      large basin (Veneneia). Vesta's geology displays morphological features
      characteristic of the Moon and terrestrial planets as well as those of other
      asteroids, underscoring Vesta's unique role as a transitional solar system body.

PMID- 22582255
TI  - The violent collisional history of asteroid 4 Vesta.
AB  - Vesta is a large differentiated rocky body in the main asteroid belt that
      accreted within the first few million years after the formation of the earliest
      solar system solids. The Dawn spacecraft extensively imaged Vesta's surface,
      revealing a collision-dominated history. Results show that Vesta's cratering
      record has a strong north-south dichotomy. Vesta's northern heavily cratered
      terrains retain much of their earliest history. The southern hemisphere was
      reset, however, by two major collisions in more recent times. We estimate that
      the youngest of these impact structures, about 500 kilometers across, formed
      about 1 billion years ago, in agreement with estimates of Vesta asteroid family
      age based on dynamical and collisional constraints, supporting the notion that
      the Vesta asteroid family was formed during this event.

PMID- 22582256
TI  - The geologically recent giant impact basins at Vesta's south pole.
AB  - Dawn's global mapping of Vesta reveals that its observed south polar depression
      is composed of two overlapping giant impact features. These large basins provide
      exceptional windows into impact processes at planetary scales. The youngest,
      Rheasilvia, is 500 kilometers wide and 19 kilometers deep and finds its nearest
      morphologic analog among large basins on low-gravity icy satellites. Extensive
      ejecta deposits occur, but impact melt volume is low, exposing an unusual spiral
      fracture pattern that is likely related to faulting during uplift and convergence
      of the basin floor. Rheasilvia obliterated half of another 400-kilometer-wide
      impact basin, Veneneia. Both basins are unexpectedly young, roughly 1 to 2
      billion years, and their formation substantially reset Vestan geology and
      excavated sufficient volumes of older compositionally heterogeneous crustal
      material to have created the Vestoids and howardite-eucrite-diogenite meteorites.

PMID- 22582257
TI  - Spectroscopic characterization of mineralogy and its diversity across Vesta.
AB  - The mineralogy of Vesta, based on data obtained by the Dawn spacecraft's visible
      and infrared spectrometer, is consistent with howardite-eucrite-diogenite
      meteorites. There are considerable regional and local variations across the
      asteroid: Spectrally distinct regions include the south-polar Rheasilvia basin,
      which displays a higher diogenitic component, and equatorial regions, which show
      a higher eucritic component. The lithologic distribution indicates a deeper
      diogenitic crust, exposed after excavation by the impact that formed Rheasilvia,
      and an upper eucritic crust. Evidence for mineralogical stratigraphic layering is
      observed on crater walls and in ejecta. This is broadly consistent with magma
      ocean models, but spectral variability highlights local variations, which
      suggests that the crust can be a complex assemblage of eucritic basalts and
      pyroxene cumulates. Overall, Vesta mineralogy indicates a complex magmatic
      evolution that led to a differentiated crust and mantle.

PMID- 22582258
TI  - Color and albedo heterogeneity of Vesta from Dawn.
AB  - Multispectral images (0.44 to 0.98 MUm) of asteroid (4) Vesta obtained by the
      Dawn Framing Cameras reveal global color variations that uncover and help
      understand the north-south hemispherical dichotomy. The signature of deep
      lithologies excavated during the formation of the Rheasilvia basin on the south
      pole has been preserved on the surface. Color variations (band depth, spectral
      slope, and eucrite-diogenite abundance) clearly correlate with distinct
      compositional units. Vesta displays the greatest variation of geometric albedo
      (0.10 to 0.67) of any asteroid yet observed. Four distinct color units are
      recognized that chronicle processes--including impact excavation, mass wasting,
      and space weathering--that shaped the asteroid's surface. Vesta's color and
      photometric diversity are indicative of its status as a preserved, differentiated
      protoplanet.

PMID- 22582259
TI  - Under the hood of the earthquake machine: toward predictive modeling of the
      seismic cycle.
AB  - Advances in observational, laboratory, and modeling techniques open the way to
      the development of physical models of the seismic cycle with potentially
      predictive power. To explore that possibility, we developed an integrative and
      fully dynamic model of the Parkfield segment of the San Andreas Fault. The model
      succeeds in reproducing a realistic earthquake sequence of irregular moment
      magnitude (M(w)) 6.0 main shocks--including events similar to the ones in 1966
      and 2004--and provides an excellent match for the detailed interseismic,
      coseismic, and postseismic observations collected along this fault during the
      most recent earthquake cycle. Such calibrated physical models provide new ways to
      assess seismic hazards and forecast seismicity response to perturbations of
      natural or anthropogenic origins.

PMID- 22582260
TI  - Ancient Maya astronomical tables from Xultun, Guatemala.
AB  - Maya astronomical tables are recognized in bark-paper books from the Late
      Postclassic period (1300 to 1521 C.E.), but Classic period (200 to 900 C.E.)
      precursors have not been found. In 2011, a small painted room was excavated at
      the extensive ancient Maya ruins of Xultun, Guatemala, dating to the early 9th
      century C.E. The walls and ceiling of the room are painted with several human
      figures. Two walls also display a large number of delicate black, red, and
      incised hieroglyphs. Many of these hieroglyphs are calendrical in nature and
      relate astronomical computations, including at least two tables concerning the
      movement of the Moon, and perhaps Mars and Venus. These apparently represent
      early astronomical tables and may shed light on the later books.

PMID- 22582261
TI  - Structural basis for DNA damage-dependent poly(ADP-ribosyl)ation by human PARP-1.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) (ADP, adenosine diphosphate) has a modular
      domain architecture that couples DNA damage detection to poly(ADP-ribosyl)ation
      activity through a poorly understood mechanism. Here, we report the crystal
      structure of a DNA double-strand break in complex with human PARP-1 domains
      essential for activation (Zn1, Zn3, WGR-CAT). PARP-1 engages DNA as a monomer,
      and the interaction with DNA damage organizes PARP-1 domains into a collapsed
      conformation that can explain the strong preference for automodification. The
      Zn1, Zn3, and WGR domains collectively bind to DNA, forming a network of
      interdomain contacts that links the DNA damage interface to the catalytic domain
      (CAT). The DNA damage-induced conformation of PARP-1 results in structural
      distortions that destabilize the CAT. Our results suggest that an increase in CAT
      protein dynamics underlies the DNA-dependent activation mechanism of PARP-1.

PMID- 22582262
TI  - Meiosis-specific noncoding RNA mediates robust pairing of homologous chromosomes
      in meiosis.
AB  - Pairing and recombination of homologous chromosomes are essential for ensuring
      reductional segregation in meiosis. However, the mechanisms by which chromosomes
      recognize their homologous partners are poorly understood. Here, we report that
      the sme2 gene encodes a meiosis-specific noncoding RNA that mediates homologous
      recognition in the fission yeast Schizosaccharomyces pombe. The sme2 locus shows
      robust pairing from early in meiotic prophase. The sme2 RNA transcripts
      accumulate at their respective gene loci and greatly enhance pairing of
      homologous loci: Deletion of the sme2 sequence eliminates this robust pairing,
      whereas transposition to other chromosomal sites confers robust pairing at those
      ectopic sites. Thus, we propose that RNA transcripts retained on the chromosome
      play an active role in recognition of homologous chromosomes for pairing.

PMID- 22582263
TI  - Recent explosive human population growth has resulted in an excess of rare
      genetic variants.
AB  - Human populations have experienced recent explosive growth, expanding by at least
      three orders of magnitude over the past 400 generations. This departure from
      equilibrium skews patterns of genetic variation and distorts basic principles of
      population genetics. We characterized the empirical signatures of explosive
      growth on the site frequency spectrum and found that the discrepancy in rare
      variant abundance across demographic modeling studies is mostly due to
      differences in sample size. Rapid recent growth increases the load of rare
      variants and is likely to play a role in the individual genetic burden of complex
      disease risk. Hence, the extreme recent human population growth needs to be taken
      into consideration in studying the genetics of complex diseases and traits.

PMID- 22582264
TI  - Use of SPME-HS-GC-MS for the analysis of herbal products containing synthetic
      cannabinoids.
AB  - The increasing prevalence and use of herbal mixtures containing synthetic
      cannabinoids presents a growing public health concern and legal challenge for
      society. In contrast to the plant-derived cannabinoids in medical marijuana and
      other cannabinoid-based therapeutics, the commonly encountered synthetic
      cannabinoids in these mendaciously labeled products constitute a structurally
      diverse set of compounds of relatively unknown pharmacology and toxicology.
      Indeed, the use of these substances has been associated with an alarming number
      of hospitalizations and emergency room visits. Moreover, there are already
      several hundred known cannabinoid agonist compounds that could potentially be
      used for illicit purposes, posing an additional challenge for public health
      professionals and law enforcement efforts, which often require the detection and
      identification of the active ingredients for effective treatment or prosecution.
      A solid-phase microextraction headspace gas chromatography-mass spectrometry
      method is shown here to allow for rapid and reliable detection and structural
      identification of many of the synthetic cannabinoid compounds that are currently
      or could potentially be used in herbal smoking mixtures. This approach provides
      accelerated analysis and results that distinguish between structural analogs
      within several classes of cannabinoid compounds, including positional isomers.
      The analytical results confirm the continued manufacture and distribution of
      herbal materials with synthetic cannabinoids and provide insight into the
      manipulation of these products to avoid legal constraints and prosecution.

PMID- 22582265
TI  - The identification of the urinary metabolites of 3-(4-methoxybenzoyl)-1
      pentylindole (RCS-4), a novel cannabimimetic, by gas chromatography-mass
      spectrometry.
AB  - 3-(4-Methoxybenzoyl)-1-pentylindole (RCS-4), a synthetic indole-derived
      cannabimimetic, was first reported to the European Monitoring Centre for Drugs
      and Drug Addiction via the Early Warning System by Hungarian authorities in 2010
      and later identified in head shop test purchases in Ireland. Using gas
      chromatography-mass spectrometry, we have identified a series of RCS-4
      metabolites in urine samples from individuals admitted to hospitals with symptoms
      of drug intoxication. The metabolites were tentatively identified as products of
      (i) aromatic monohydroxylation; (ii) dihydroxylation; (iii) aromatic
      hydroxylation/oxidation of the N-pentyl chain to a ketone; (iv) O-demethylation;
      (v) O-demethylation/monohydroxylation of N-pentyl chain; (vi) O
      demethylation/oxidation of the N-pentyl chain to a ketone; (vii) O
      demethylation/aromatic hydroxylation/oxidation of the N-pentyl chain to a ketone;
      (viii) N-depentylation/aromatic monohydroxylation; and (ix) N and O-dealkylation.
      The parent compound was not detected. The O-demethylated metabolites were found
      to be the most useful metabolic markers for the identification of RCS-4
      ingestion.

PMID- 22582266
TI  - Simultaneous determination of xylazine, free morphine, codeine, 6-acetylmorphine,
      cocaine and benzoylecgonine in postmortem blood by UPLC-MS-MS.
AB  - Xylazine, a veterinary sedative, has been found as an adulterant of heroin in
      street drugs in Puerto Rico. It was found in combination with free morphine and 6
      acetylmorphine, codeine, cocaine and benzoylecgonine in postmortem cases at the
      Puerto Rico Institute of Forensic Sciences (PRIFS). Xylazine is not approved for
      human use because it has been proven harmful. Currently, three separate analyses
      are required to determine all the aforementioned drugs at the PRIFS's toxicology
      laboratory. To reduce analysis time consumption, sample volume, run time, sample
      preparation and cost, a high-throughput ultra-high-pressure liquid chromatography
      tandem mass spectrometry method was developed and validated for the simultaneous
      quantification of xylazine, free morphine, 6-acetylmorphine, codeine, cocaine and
      benzoylecgonine in 0.25 mL postmortem blood by protein precipitation, fulfilling
      confirmation criteria with three transitions for each compound with acceptable
      relative ion intensities. Linearity was established between 10-1,000 ng/mL. Total
      run time was 2.5 min. Limit of detection was 1 ng/mL for cocaine and xylazine, 2
      ng/mL for 6-acetylmorphine and 10 ng/mL for free morphine, codeine and
      benzoylecgonine. The intra-day and inter-day precision and accuracy was less than
      15.6%. Process efficiencies ranged from 35.9 to 123.4% and recoveries from 59.9
      to 110.1%. The developed method was successfully applied to casework.

PMID- 22582267
TI  - Rapid and sensitive analysis of 3,4-methylenedioxypyrovalerone in equine plasma
      using liquid chromatography-tandem mass spectrometry.
AB  - 3,4-Methylenedioxypyrovalerone (MDPV) is a psychoactive drug with potent
      stimulant properties and potential for abuse and drug dependency. MDPV was
      recently classified as a Class I drug by Racing Commissioners International,
      indicating that it is a banned substance in equine athletes because it lacks
      therapeutic value in horses. To enforce this ban, a sensitive and fast liquid
      chromatography-tandem mass spectrometry method was needed. It is for this reason
      that this method was developed for quantification and confirmation of MDPV in
      equine plasma. Sample preparation involved liquid-liquid extraction. The analyte
      was analyzed by a triple-quadrupole linear ion trap mass spectrometer in positive
      multiple-reaction-monitoring and enhanced product ion scan modes. The method was
      validated for precision, accuracy, limit of detection (LOD), limit of
      quantification (LOQ), linearity, stability, extraction recovery, matrix effect,
      dilution accuracy and selectivity. The extraction recovery was >90%. The
      linearity range was from 5 to 15,000 pg/mL. LOD and LOQ were 2 and 5 pg/mL,
      respectively. Intra-day and inter-day accuracies were nearly 100%. The method is
      suitable for screening, quantification and confirmation of MDPV in equine plasma
      and has been successfully used to detect and confirm the presence of MDPV in
      equine plasma obtained post-competition.

PMID- 22582268
TI  - The determination of occupational exposure to polycyclic aromatic hydrocarbons by
      the analysis of 1-hydroxypyrene in urine using a simple automated online column
      switching device and high-performance liquid chromatography.
AB  - An analytical method using a liquid chromatograph combined with a simple online
      column switching sample pre-treatment system was developed for the determination
      of 1-hydroxypyrene (1-HP) in urine. This compound is the metabolite of pyrene and
      is used to assess the exposure of workers to polycyclic aromatic hydrocarbons
      (PAHs). After enzymatic hydrolysis, a urine sample was directly injected into a
      high-performance liquid chromatograph (HPLC) where it automatically underwent a
      sample cleanup using a column switching device. The procedure is simpler than
      previous methods because it uses only one switching valve, one extraction column
      and one HPLC pump. The analyte was retained on a short extraction column and
      after interferences were eluted to waste, was subsequently switched onto the
      analytical column. This allowed a short analysis time of 15 min. The calibration
      graph was found to be linear within the concentration range of 0.5 to 20 ug/L
      with a coefficient of determination exceeding r(2) = 0.99. Recoveries were found
      to be greater than 96% in the range 1 to 10 ug/L with intermediate precision of
      2.5 to 5.8% relative standard deviation. This online method was verified by a
      comparison with an existing manual method by the analysis of 81 urine samples
      from workers exposed to PAHs and showed that the test results from both methods
      were in agreement with a probability obtained from the paired Student's t-test of
      P > 0.76. The proposed online method was found to be simple, fast and suited to
      routine analyses of 1-HP in urine for the assessment of occupational exposure to
      PAHs.

PMID- 22582269
TI  - Comparison of five derivatizing agents for the determination of amphetamine-type
      stimulants in human urine by extractive acylation and gas chromatography-mass
      spectrometry.
AB  - Five acylation reagents have been compared for use as derivatizing agents for the
      analysis of amphetamine-type stimulants (ATS) in urine by gas chromatography-mass
      spectrometry (GC-MS). The evaluated reagents were heptafluorobutyric anhydride,
      pentafluoropropionic anhydride, trifluoroacetic anhydride, acetic anhydride (AA)
      and N-methyl-bis(trifluoroacetamide). The ATS included amphetamine,
      methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4
      methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyethylamphetamine
      (MDEA). A mixture of the ATS was added to urine (1 mL) followed by KOH solution
      and saturated NaHCO(3) solution. The sample was then extracted with
      dichloromethane and the derivatizing agent and 2 uL were injected into the GC-MS
      instrument. The derivatizing agents were compared with reference to the signal-to
      noise (S/N) ratios, peak area values, relative standard deviations (RSDs),
      linearities, limits of detection (LODs) and selectivities. The acetic anhydride
      proved to be the best according to the S/N ratio and peak area results for
      amphetamine, MA, MDMA and MDEA. The best RSD values of peak areas and of S/N
      ratios at 3 ug/mL were also given by AA in cases of MDA, MDMA and MDEA. At 20
      ug/mL, the lowest RSD values of peak areas for MDA and the lowest RSD values of
      S/N ratios for MA, MDA, MDMA and MDEA were again given by AA. Additionally, the
      highest correlation coefficients for MA, MDA, MDMA and MDEA and the lowest LOD
      results for MA, MDMA and MDEA were produced by AA.

PMID- 22582270
TI  - Method comparison of the Ortho Vitros Fusion 5,1 chemistry analyzer and the Roche
      COBAS Integra 400 for urine drug screen testing in the emergency department.
AB  - Exposure to drugs and toxins is a major cause for the rising number of emergency
      department visits each year. Immunoassays are commonly used in the emergency
      department to provide rapid turnaround time for acute care. The purpose of this
      study was to compare two automated immunoassay chemistry analyzers to determine
      which platform produced the fewest number of false positive/negative results.
      Residual patient urine samples were were collected for each of the following
      drugs/drug classes: cocaine (n = 40), opiates (n = 45), and amphetamines (n = 54)
      and confirmed either positive or negative by mass spectrometry. Split sample
      analyses of these specimens were performed on both the Roche COBAS INTEGRA 400
      plus and Ortho Vitros 5,1 FS instruments. The results from the two chemistry
      analyzers were compared to confirmed results. Both immunoassays were prone to
      false positive results for cocaine and false negative results for opiates and
      amphetamines. The Vitros Fusion analyzer generated fewer false positive and false
      negative results for opiate and amphetamine testing than the Roche Integra, but
      the platforms performed comparably for cocaine.

PMID- 22582271
TI  - Distribution of embutramide and mebezonium iodide in a suicide after tanax
      injection.
AB  - Tanax is a veterinary formulation for euthanasia comprising embutramide,
      mebezonium iodide and tetracaine. A 37-year-old female was found dead on her bed,
      with three empty used syringes and a bottle of Tanax beside her body. Three
      needle puncture marks were observed on the body. The aim of this study was to
      evaluate the distribution of embutramide and mebezonium iodide in different
      biological matrices (femoral and cardiac blood, liver, muscle and vitreous humor)
      using a chromatographic method for the simultaneous determination of the two
      drugs. A direct and sensitive liquid chromatography-tandem mass spectrometry
      method was developed in multiple reaction monitoring mode with positive
      ionization. Lidocaine was used as an internal standard. Limits of detection and
      quantitation of 0.01 and 0.05 mg/L, respectively, were reached for both
      compounds. Embutramide levels ranged from 2.74 mg/L in vitreous humor to 5.06
      mg/L in femoral blood, while mebezonium iodide was found at widely differing
      concentrations (ranging from 2.80 mg/kg in muscle to 24.80 mg/kg in liver). The
      chromatographic method developed for this study provides a very simple and
      sensitive means for the simultaneous determination of embutramide and mebezonium
      iodide, the emetic concentrations of which were consistent with suicides reported
      in the literature.

PMID- 22582272
TI  - The mirage of impairing drug concentration thresholds: a rationale for zero
      tolerance per se driving under the influence of drugs laws.
AB  - Motor vehicle crashes are a leading cause of morbidity and mortality in the
      United States. Drivers with measurable quantities of potentially impairing
      illicit or prescription drugs in their body fluids are multiple times more likely
      to be involved in motor vehicle crashes than those without such drugs in their
      bodies. Drug-related impairment, however, cannot be inferred solely on the basis
      of the presence of drugs in biological fluids. Thus, for more than a quarter
      century, there has been a search for drug blood concentrations that are the
      equivalent of the 0.08 g/dL threshold for alcohol-impaired driving in the United
      States. We suggest that such equivalents are a mirage, and cannot be determined
      due to variable drug tolerance, lack of consistent relationships between drug
      blood concentrations and impairment, innumerable drug combinations and multiple
      other factors. Thus, while the idea of determining impairing drug concentrations
      is attractive, it is ultimately unattainable, and withholding drugged driving
      legislation pending the acquisition of such data is tantamount to a plan for
      inaction with regard to an important and growing public health and safety
      problem. We propose specific legislation to address alcohol- and drug-impaired
      driving in the United States.

PMID- 22582274
TI  - Response to "Is THCCOOH a useful determinant for passive inhalation in oral fluid
      THC testing?".

PMID- 22582275
TI  - Electron bifurcation involved in the energy metabolism of the acetogenic
      bacterium Moorella thermoacetica growing on glucose or H2 plus CO2.
AB  - Moorella thermoacetica ferments glucose to three acetic acids. In the oxidative
      part of the fermentation, the hexose is converted to 2 acetic acids and 2 CO(2)
      molecules with the formation of 2 NADH and 2 reduced ferredoxin (Fd(red)(2-))
      molecules. In the reductive part, 2 CO(2) molecules are reduced to acetic acid,
      consuming the 8 reducing equivalents generated in the oxidative part. An open
      question is how the two parts are electronically connected, since two of the four
      oxidoreductases involved in acetogenesis from CO(2) are NADP specific rather than
      NAD specific. We report here that the 2 NADPH molecules required for CO(2)
      reduction to acetic acid are generated by the reduction of 2 NADP(+) molecules
      with 1 NADH and 1 Fd(red)(2-) catalyzed by the electron-bifurcating NADH
      dependent reduced ferredoxin:NADP(+) oxidoreductase (NfnAB). The cytoplasmic iron
      sulfur flavoprotein was heterologously produced in Escherichia coli, purified,
      and characterized. The purified enzyme was composed of 30-kDa (NfnA) and 50-kDa
      (NfnB) subunits in a 1-to-1 stoichiometry. NfnA harbors a [2Fe2S] cluster and
      flavin adenine dinucleotide (FAD), and NfnB harbors two [4Fe4S] clusters and FAD.
      M. thermoacetica contains a second electron-bifurcating enzyme. Cell extracts
      catalyzed the coupled reduction of NAD(+) and Fd with 2 H(2) molecules. The
      specific activity of this cytoplasmic enzyme was 3-fold higher in H(2)-CO(2)
      grown cells than in glucose-grown cells. The function of this electron
      bifurcating hydrogenase is not yet clear, since H(2)-CO(2)-grown cells
      additionally contain high specific activities of an NADP(+)-dependent hydrogenase
      that catalyzes the reduction of NADP(+) with H(2). This activity is hardly
      detectable in glucose-grown cells.

PMID- 22582276
TI  - Flavobacterium johnsoniae RemA is a mobile cell surface lectin involved in
      gliding.
AB  - Cells of Flavobacterium johnsoniae move rapidly over surfaces by a process known
      as gliding motility. Gld proteins are thought to comprise the motor that propels
      the cell surface adhesin SprB. Cells with mutations in sprB are partially
      defective in motility and are also resistant to some bacteriophages. Transposon
      mutagenesis of a strain carrying a deletion spanning sprB identified eight
      mutants that were resistant to additional phages and exhibited reduced motility.
      Four of the mutants had transposon insertions in remA, which encodes a cell
      surface protein that has a lectin domain and appears to interact with
      polysaccharides. Three other genes identified in this screen (remC, wza, and wzc)
      encode proteins predicted to be involved in polysaccharide synthesis and
      secretion. Myc-tagged versions of RemA localized to the cell surface and were
      propelled rapidly along the cell at speeds of 1 to 2 MUm/s. Deletion of gldN and
      gldO, which encode components of a bacteroidete protein secretion system, blocked
      the transport of RemA to the cell surface. Overexpression of RemA resulted in the
      formation of cell aggregates that were dispersed by the addition of galactose or
      rhamnose. Cells lacking RemC, Wza, and Wzc failed to aggregate. Cells of a remC
      mutant and cells of a remA mutant, neither of which formed aggregates in
      isolation, aggregated when they were mixed together, suggesting that
      polysaccharides secreted by one cell may interact with RemA on another cell.
      Fluorescently labeled lectin Ricinus communis agglutinin I detected
      polysaccharides secreted by F. johnsoniae. The polysaccharides bound to cells
      expressing RemA and were rapidly propelled on the cell surface. RemA appears to
      be a mobile cell surface adhesin, and secreted polysaccharides may interact with
      the lectin domain of RemA and enhance motility.

PMID- 22582277
TI  - Autocatalytic maturation of the Tat-dependent halophilic subtilase Nep produced
      by the archaeon Natrialba magadii.
AB  - Halolysins are subtilisin-like extracellular proteases produced by haloarchaea
      that possess unique protein domains and are salt dependent for structural
      integrity and functionality. In contrast to bacterial subtilases, the maturation
      mechanism of halolysins has not been addressed. The halolysin Nep is secreted by
      the alkaliphilic haloarchaeon Natrialba magadii, and the recombinant active
      enzyme has been synthesized in Haloferax volcanii. Nep contains an N-terminal
      signal peptide with the typical Tat consensus motif (GRRSVL), an N-terminal
      propeptide, the protease domain, and a C-terminal domain. In this study, we used
      Nep as a model protease to examine the secretion and maturation of halolysins by
      using genetic and biochemical approaches. Mutant variants of Nep were constructed
      by site-directed mutagenesis and expressed in H. volcanii, which were then
      analyzed by protease activity and Western blotting. The Tat dependence of Nep
      secretion was demonstrated in Nep RR/KK variants containing double lysine (KK) in
      place of the twin arginines (RR), in which Nep remained cell associated and the
      extracellular activity was undetectable. High-molecular-mass Nep polypeptides
      without protease activity were detected as cell associated and extracellularly in
      the Nep S/A variant, in which the catalytic serine 352 had been changed by
      alanine, indicating that Nep protease activity was needed for precursor
      processing and activation. Nep NSN 1-2 containing a modification in two potential
      cleavage sites for signal peptidase I (ASA) was not efficiently processed and
      activated. This study examined for the first time the secretion and maturation of
      a Tat-dependent halophilic subtilase.

PMID- 22582278
TI  - Salmonella biofilm development depends on the phosphorylation status of RcsB.
AB  - The Rcs phosphorelay pathway is a complex signaling pathway involved in the
      regulation of many cell surface structures in enteric bacteria. In response to
      environmental stimuli, the sensor histidine kinase (RcsC) autophosphorylates and
      then transfers the phosphate through intermediary steps to the response regulator
      (RcsB), which, once phosphorylated, regulates gene expression. Here, we show that
      Salmonella biofilm development depends on the phosphorylation status of RcsB.
      Thus, unphosphorylated RcsB, hitherto assumed to be inactive, is essential to
      activate the expression of the biofilm matrix compounds. The prevention of RcsB
      phosphorylation either by the disruption of the phosphorelay at the RcsC or RcsD
      level or by the production of a nonphosphorylatable RcsB allele induces biofilm
      development. On the contrary, the phosphorylation of RcsB by the constitutive
      activation of the Rcs pathway inhibits biofilm development, an effect that can be
      counteracted by the introduction of a nonphosphorylatable RcsB allele. The
      inhibition of biofilm development by phosphorylated RcsB is due to the repression
      of CsgD expression, through a mechanism dependent on the accumulation of the
      small noncoding RNA RprA. Our results indicate that unphosphorylated RcsB plays
      an active role for integrating environmental signals and, more broadly, that RcsB
      phosphorylation acts as a key switch between planktonic and sessile life-styles
      in Salmonella enterica serovar Typhimurium.

PMID- 22582279
TI  - DivIVA-mediated polar localization of ComN, a posttranscriptional regulator of
      Bacillus subtilis.
AB  - ComN (YrzD) is a small, 98-amino-acid protein recently shown to be involved in
      the posttranscriptional control of the late competence comE operon in Bacillus
      subtilis. We show here that ComN localizes to the division site and cell poles in
      a DivIVA-dependent fashion. Yeast two-hybrid and glutathione S-transferase
      pulldown experiments showed that ComN interacts directly with DivIVA. ComN is not
      essential for the polar assembly of the core competence DNA uptake machinery.
      Nevertheless, polar localization of ComN should play some role in competence
      acquisition because delocalization of ComN leads to a small reduction in
      competence efficiency. We found that ComN promotes the accumulation of its target
      comE mRNA to septal and polar sites. Thus, we speculate that localized
      translation of ComE proteins may be required for efficient competence
      development. Our results underscore the versatility of DivIVA as a promoter of
      the differentiation of bacterial poles and demonstrate that the repertoire of
      polarly localized molecules in B. subtilis is broad, including a regulator of
      gene expression and its target mRNA. Moreover, our findings suggest that mRNA
      localization may play a role in the subcellular organization of bacteria.

PMID- 22582280
TI  - Contributions of individual sigmaB-dependent general stress genes to oxidative
      stress resistance of Bacillus subtilis.
AB  - The general stress regulon of Bacillus subtilis comprises approximately 200 genes
      and is under the control of the alternative sigma factor sigma(B). The activation
      of sigma(B) occurs in response to multiple physical stress stimuli as well as
      energy starvation conditions. The expression of the general stress proteins
      provides growing and stationary nonsporulating vegetative cells with nonspecific
      and broad stress resistance. A previous comprehensive phenotype screening
      analysis of 94 general stress gene mutants in response to severe growth
      inhibiting stress stimuli, including ethanol, NaCl, heat, and cold, indicated
      that secondary oxidative stress may be a common component of severe physical
      stress. Here we tested the individual contributions of the same set of 94 mutants
      to the development of resistance against exposure to the superoxide-generating
      agent paraquat and hydrogen peroxide (H(2)O(2)). In fact, 62 mutants displayed
      significantly decreased survival rates in response to paraquat and/or H(2)O(2)
      stress compared to the wild type at a confidence level of an alpha value of <=
      0.01. Thus, we were able to assign 47 general stress genes to survival against
      superoxide, 6 genes to protection from H(2)O(2) stress, and 9 genes to the
      survival against both. Furthermore, we show that a considerable overlap exists
      between the phenotype clusters previously assumed to be involved in oxidative
      stress management and the actual group of oxidative-stress-sensitive mutants. Our
      data provide information that many general stress proteins with still unknown
      functions are implicated in oxidative stress resistance and further support the
      notion that different severe physical stress stimuli elicit a common secondary
      oxidative stress.

PMID- 22582281
TI  - Why we like clinical guidelines.

PMID- 22582283
TI  - Future considerations in poultry nutrition.
AB  - Following is invited commentary on the symposium "A Crystal Ball Look into the
      Future of..." delivered July 16, 2011, at the Poultry Science Association's 100th
      annual meeting, St. Louis, Missouri. The symposium examined various aspects that
      will impact the future of poultry production over the next 10 to 20 yr. Topics
      included genetics, nutrition, incubation, and bird health. This paper deals with
      various aspects of future issues affecting global feeding and nutrition of
      poultry.

PMID- 22582284
TI  - Immune modulation of innate immunity as alternatives-to-antibiotics strategies to
      mitigate the use of drugs in poultry production.
AB  - Following is invited commentary on the symposium "A Crystal Ball Look into the
      Future of..." delivered July 16, 2011, at the Poultry Science Association's 100th
      annual meeting, St. Louis, Missouri. The symposium examined various aspects that
      will impact the future of poultry production over the next 10 to 20 yr. Topics
      included genetics, nutrition, incubation, and bird health. This paper deals with
      various aspects of future issues affecting global feeding and nutrition of
      poultry.

PMID- 22582285
TI  - Genetic parameters of egg defects and egg quality in layer chickens.
AB  - Genetic parameters were estimated for egg defects, egg production, and egg
      quality traits. Eggs from 11,738 purebred brown-egg laying hens were classified
      as salable or as having one of the following defects: bloody, broken, calcium
      deposit, dirty, double yolk, misshapen, pee-wee, shell-less, and soft shelled.
      Egg quality included albumen height, egg weight, yolk weight, and puncture score.
      Body weight, age at sexual maturity, and egg production were also recorded.
      Heritability estimates of liability to defects using a threshold animal model
      were less than 0.1 for bloody and dirty; between 0.1 and 0.2 for pee-wee, broken,
      misshapen, soft shelled, and shell-less; and above 0.2 for calcium deposit and
      double yolk. Quality and production traits were more heritable, with estimates
      ranging from 0.29 (puncture score) to 0.74 (egg weight). High-producing hens had
      a lower frequency of egg defects. High egg weight and BW were associated with an
      increased frequency of double yolks, and to a lesser extent, with more shell
      quality defects. Estimates of genetic correlations among defect traits that were
      related to shell quality were positive and moderate to strong (0.24-0.73),
      suggesting that these could be grouped into one category or selection could be
      based on the trait with the highest heritability or that is easiest to measure.
      Selection against defective eggs would be more efficient by including egg defect
      traits in the selection criterion, along with egg production rate of salable eggs
      and egg quality traits.

PMID- 22582286
TI  - Polymorphisms in Wnt signaling pathway genes are significantly associated with
      chicken carcass traits.
AB  - The Wnt signaling pathway plays a crucial role during embryogenesis in
      vertebrates. In this study, 124 SNP in 31 Wnt signaling pathway genes were
      selected to genotype 764 individuals in an F(2) resource population by
      reciprocally crossing Silkie fowls and Cornish broilers, and 102 SNP were
      polymorphic. Pairwise linkage disequilibrium among the SNP within each gene was
      calculated. Haplotypes were reconstructed from the SNP in strong linkage
      disequilibrium. The associations of SNP and haplotypes with carcass traits were
      analyzed respectively, and the SNP contributions to phenotypic variance were
      estimated. The present study showed that 58 SNP in 24 genes and 8 haplotype
      blocks within 7 genes were significantly (P < 0.05) associated with at least one
      carcass trait. Fourteen SNP (among the 58 SNP) explained >2% phenotypic variance,
      12 of which had significantly (P < 0.01) additive or dominant effects.
      Furthermore, both rs15865526 (Wnt9A) and rs14066777 (MAPK9) as well as their
      corresponding haplotype blocks were significantly associated with shank
      circumference and wing weight, respectively. In addition, 5 muscle-weight-related
      SNP explained >7% phenotypic variance, which was much higher than those of
      others. It was found that the Wnt signaling pathway was strongly associated with
      chicken carcass traits, and 7 genes were particularly important, namely RHOA and
      CHP for breast muscle weight, Wnt3A for breast muscle weight percentage over
      carcass weight, RAC1 for thigh weight percentage and thigh muscle weight
      percentage over carcass weight, Wnt11 for thigh weight percentage over carcass
      weight, Wnt9A for shank length, and MAPK9 for shank circumference. It is evident
      that Wnt signaling plays a major role in regulating carcass characteristics
      important for production traits in chickens.

PMID- 22582287
TI  - An initial safety assessment of hepatotoxic and nephrotoxic potential of
      intramuscular ketoprofen at single repetitive dose level in broiler chickens.
AB  - A study was undertaken to assess the hepatotoxic and nephrotoxic potential of
      ketoprofen in comparison with diclofenac upon short-term intramuscular (i.m.)
      administration in broiler chickens. Eighteen broiler chickens were randomly
      divided into 3 groups of 6 birds each. Group I served as the control and received
      normal saline (0.1 mL, i.m.), group II was the positive control and received
      diclofenac sodium (2.5 mg/kg, i.m.), and group III received ketoprofen (3 mg/kg,
      i.m.) daily at 24-h intervals for 5 consecutive days. Diclofenac sodium-treated
      birds showed severe clinical signs of toxicity with high mortality, a significant
      increase (P < 0.01) in serum concentrations of creatinine, uric acid, alanine
      aminotransferase, and aspartate aminotransferase, and these changes correlated
      well with gross and microscopic examination findings of kidney and liver. In
      contrast, ketoprofen-treated birds did not show any adverse clinical signs and no
      significant increase in concentration of creatinine, uric acid, alanine
      aminotransferase, and aspartate aminotransferase when compared with birds in
      group I. Gross and microscopic examination of kidney and liver showed normal
      organ architecture. Thus, based on the present findings, it was concluded that
      ketoprofen at the dose of 3 mg/kg administered intramuscularly daily for 5 d was
      nontoxic to broiler chickens.

PMID- 22582288
TI  - Differentially expressed genes in aortic smooth muscle cells from atherosclerosis
      susceptible and atherosclerosis-resistant pigeons.
AB  - Susceptibility to spontaneous atherosclerosis in the White Carneau (WC-As) pigeon
      shows autosomal recessive inheritance. Aortic smooth muscle cells (SMC) cultured
      from susceptible WC-As and resistant Show Racer (SR-Ar) pigeons exhibit
      developmental and degenerative features corresponding to the respective SMC at
      atherosclerosis-prone sites in vivo. We used representational difference analysis
      to identify differentially expressed genes between WC-As and SR-Ar aortic SMC.
      Total RNA was extracted from cultured primary SMC of each breed, converted to
      double-stranded cDNA, followed by direct comparison in reciprocal
      representational difference analysis experiments. Difference products were
      cloned, sequenced, and identified by BLAST against the chicken genome. Six
      putative biochemical pathways were distinctly different between breeds with genes
      involved in energy metabolism and contractility exhibiting the most striking
      disparity. Genes associated with glycolysis and a synthetic SMC phenotype were
      expressed in WC-As cells. In contrast, SR-Ar cells expressed genes indicative of
      oxidative phosphorylation and a contractile SMC phenotype. In WC-As cells, the
      alternatives of insufficient ATP production limiting contractile function or the
      lack of functional contractile elements downregulating ATP synthesis cannot be
      distinguished due to the compressed in vitro versus in vivo developmental time
      frame. However, the genetic potential for effectively coupling energy production
      to muscle contraction present in the resistant SR-Ar was lacking in the
      susceptible WC-As.

PMID- 22582289
TI  - Effects of in ovo interleukin-4-plasmid injection on anticoccidia immune response
      in a coccidia infection model of chickens.
AB  - Two experiments were conducted to study the effects of an in ovo interleukin (IL)
      4 plasmid injection in a coccidia infection model. In experiment I, chicks were
      hatched from eggs that had been injected in ovo with an empty vector or with 10
      or 15 MUg of IL-4 plasmid, and then challenged posthatch with coccidia. In
      experiment II, chicks were hatched from eggs that had been vaccinated with
      coccidia and injected in ovo with an empty vector or with 10 or 15 MUg of IL-4
      plasmid, and then challenged posthatch with coccidia. In experiment II, the BW
      gain of birds hatched from eggs vaccinated with live oocysts plus 15 MUg of IL-4
      plasmid was 25% higher than the BW gain of birds hatched from eggs vaccinated
      with live oocysts plus empty plasmid. In both experiments I and II, a 15-MUg IL-4
      plasmid injection decreased fecal oocyst shedding, decreased the number of CD8(+)
      cells in the cecal tonsils, and decreased cecal tonsil lymphocyte cell
      proliferation postcoccidia challenge. In experiment I, splenic macrophages of
      chicks hatched from eggs injected with 15 MUg of IL-4 plasmid had higher nitric
      oxide production than those of chicks hatched from eggs injected with the empty
      plasmid. In experiment II, a 15-MUg IL-4-plasmid injection increased serum
      anticoccidia IgG postcoccidia challenge. It could be concluded that 15 MUg of IL
      4 plasmid improved anticoccidia immune responses synergistically with in ovo
      coccidia vaccination in chickens.

PMID- 22582290
TI  - Quantitative analyses of genes associated with mucin synthesis of broiler
      chickens with induced necrotic enteritis.
AB  - Clostridial infection of the intestine can result in necrotic enteritis (NE),
      compromising production and health of poultry. Mucins play a major role in
      protecting the intestinal epithelium from infection. The relative roles of
      different mucins in gut pathology following bacterial challenge are unclear. This
      study was designed to quantify the expression of mucin and mucin-related genes,
      using intestinal samples from an NE challenge trial where birds were fed diets
      with or without in-feed antimicrobials. A method for quantifying mucin gene
      expression was established using a suite of reference genes to normalize
      expression data. This method was then used to quantify the expression of 11
      candidate genes involved in mucin, inflammatory cytokine, or growth factor
      biosynthesis (IL-18, KGF, TLR4, TFF2, TNF-alpha, MUC2, MUC4, MUC5ac, MUC5b,
      MUC13, and MUC16). The only genes that were differentially expressed in the
      intestine among treatment groups were MUC2, MUC13, and MUC5ac. Expression of MUC2
      and MUC13 was depressed by co-challenge with Eimeria spp. and Clostridium
      perfringens. Antimicrobial treatment prevented an NE-induced decrease in MUC2
      expression but did not affect MUC13. The expression of MUC5ac was elevated in
      birds challenged with Eimeria spp./C. perfringens compared with unchallenged
      controls and antimicrobial treatment. Changes to MUC gene expression in
      challenged birds is most likely a consequence of severe necrosis of the jejunal
      mucosa.

PMID- 22582291
TI  - The composition of egg yolk absorbed by fasted ostrich (Struthio camelus L.)
      chicks from 1 to 7 days posthatching and for ostrich (Struthio camelus L.) chicks
      from 1 to 16 days posthatching on a prestarter broiler diet.
AB  - This study was performed to obtain information on yolk utilization in fasted and
      fed ostrich chicks posthatching. The fasted trial lasted for 7 d, whereas the fed
      trial continued for 16 d. Fasted ostrich chicks showed a decrease of 31.3 g of
      BW, with yolk weight decreasing by 28.9 g daily after hatching. Yolk weight
      comprised 28% of 1-d-old ostrich chick BW and decreased to 12% at 7 d of age.
      Only 44.4% of the fasted ostrich chick yolk was assimilated over the trial
      period. Crude protein content of the yolk decreased by 13.2 g daily. Fat content
      increased by 1.77% daily, whereas total yolk fat weight decreased with 8.91 g
      daily. Slaughter weight of fed ostrich chicks increased, with yolk weight
      decreasing by 16.3 g daily. Yolk content for fed ostrich chicks was 26% of BW at
      2 d of age. Ostrich chicks absorb 30% of yolk over the first 4 d, 67% after 8 d,
      and only deplete the yolk after 14 d posthatch. Fasted ostrich chicks absorbed
      the yolk content at a rate of 28.9 g/d, compared with 22.3 g/d over the first 8 d
      and 16.3 g/d over the 16 d for fed ostrich chicks. The CP content of the yolk
      decreased by 6.84 g daily in fed ostrich chicks, whereas fat content of the yolk
      increased by 1.39% daily, although total yolk fat weight decreased by 6.61 g
      daily. Yolk weight and total CP decreased faster over the first 7 d in the fasted
      ostrich chicks compared with the fed ostrich chicks, which indicated that the
      decrease in yolk weight could be attributed to absorption of protein from the
      yolk. Fat content decreased faster over the first 8 d from the yolk of the fed
      ostrich chicks compared with that from the yolk of the fasted ostrich chicks,
      which could indicate that external feed has a positive influence on the
      absorption of fat from the yolk content.

PMID- 22582292
TI  - Comparison of amino acid digestibility coefficients for soybean meal, canola
      meal, fish meal, and meat and bone meal among 3 different bioassays.
AB  - The objective of this study was to determine amino acid digestibility of 4
      feedstuffs [soybean meal (SBM), canola meal, fish meal, and meat and bone meal
      (MBM)] using the precision-fed cecectomized rooster assay (PFR), the standardized
      ileal assay (SIAAD), and a newly developed precision-fed ileal broiler assay
      (PFC). For the PFR, cecectomized roosters were precision-fed approximately 30 g
      of feed sample, and excreta were collected 48 h postfeeding. For the SIAAD, 16-d
      old broilers were fed a semipurified diet containing the feed samples as the only
      source of protein from 17 to 21 d, with ileal digesta collected at 21 d. For the
      PFC, 22-d-old broilers were precision-fed 10 g of feed sample mixed with chromic
      oxide, and ileal digesta were collected at 4 h postfeeding. Digestibility
      coefficients were standardized using a nitrogen-free diet for the SIAAD and PFC
      and using fasted roosters for the PFR. There were generally no consistent
      differences in standardized amino acid digestibility values among assays, and
      values were in general agreement among assays, particularly for SBM and MBM.
      Differences did occur among methods for amino acid digestibility in fish meal;
      however, these differences were not consistent among methods or amino acids. The
      results of the study indicated that all 3 bioassays are acceptable for
      determining the amino acid digestibility of SBM, canola meal, MBM, and fish meal
      for poultry.

PMID- 22582293
TI  - The effect of reduced calorie diets, with and without fat, and the use of
      xylanase on performance characteristics of broilers between 0 and 42 days.
AB  - When decreasing the energy value of broiler diets, nonstarch polysaccharide
      degrading enzymes, such as xylanase, are often used. In doing so, they are
      assigned an energy value and considered to contribute energy to the diet. The aim
      of this study was to determine the effect of decreasing energy in a broiler diet
      by 100 kCal/kg on performance and whether the expected drop in performance could
      be recovered with the use of xylanase. Two formulations were used to provide
      decreased energy diets, both with and without supplementary fat. Six hundred 1-d
      old male Cobb broilers were placed in a 2 * 3 full factorial design in 5
      randomized complete blocks. The treatments were enzyme dose at 0 or 16,000 U/kg,
      and the 3 different diets [positive control (PC), negative control 1, without fat
      (NC1), and negative control 2 with fat (NC2)]. At no point were there any
      interactions between diet type and enzyme inclusion; where there was an effect of
      xylanase, it was consistent regardless of the diet type. There was a significant
      effect of diet type on feed intake between d 0 to 35; NC1 and NC2 had
      significantly increased feed intake compared with the PC (P = 0.006). The feed
      conversion ratio was significantly increased in birds fed the negative control
      diets during 0 to 35 d and 0 to 42 d (P = 0.003 and P = 0.002, respectively).
      However, feed conversion ratio was significantly improved by the addition of
      enzyme during periods 0 to 35 d and 0 to 42 d. There were no significant main
      effects between d 0 and 21 (all responses P > 0.1). Liveability was not affected
      by any of the treatments (P > 0.1). Decreasing energy in broiler diets results in
      worsened performance. The use of xylanase may improve feed conversion ratio. The
      use of some fat may help, so the whole diet composition should be considered in
      conjunction with enzyme dose to achieve the best advantage.

PMID- 22582294
TI  - Intra-amniotic administration and dietary inulin affect the iron status and
      intestinal functionality of iron-deficient broiler chickens.
AB  - Inulin, a linear beta-fructan, is present in a variety of plants, with relatively
      high levels of up to 20% in chicory root. It exhibits prebiotic properties and
      was shown to enhance mineral absorption. Our objectives were to assess the effect
      of intra-amniotic administration of inulin at 17 d of incubation on the iron
      status of broiler chicks (at hatch, 21 d) and to continue to monitor iron status
      with and without dietary inulin on these hatchlings for 42 d. The study included
      3 prehatch treatment groups (n = 30): 1) inulin, inulin solution (4% inulin/0.85%
      saline); 2) control 1, untreated eggs; and 3) control 2, saline solution (0.85%
      saline). Solutions were injected into the naturally consumed amniotic fluid of 17
      d-old chicken embryos (groups 1, 3). Upon hatch (93% hatchability), and from each
      group, 10 chicks were killed and their small intestine, liver, and cecum were
      removed for mRNA abundance of intestinal iron-related transporters, liver
      ferritin amounts, and bacterial analysis of cecal content, respectively. From the
      remaining chicks of each group, chicks were allocated to a standard corn-based
      diet (+/- 4% inulin, n = 10). During the trial, hemoglobin concentrations and
      body hemoglobin-Fe values were higher in the inulin group versus controls (P <
      0.05). On d 42, birds were anesthetized and their duodenal loops were exposed. A
      nonocclusive catheter was inserted into the duodenal vein for blood sampling. A
      solution containing 58Fe (0.1 mg of Fe/10 mM ascorbic acid) added to the digested
      diet sample was injected into the loop. Blood samples were collected every 5 min
      and for 90 min postinjection and analyzed by inductively coupled argon-plasma
      mass spectrometry for 58Fe concentrations. At the end of the procedure, animals
      were killed and cecum contents and sections of the duodenum and liver were
      removed. Results showed that 58Fe absorption rates were at times higher in the
      inulin group versus the other groups. Also, mRNA abundance of DMT1 (an Fe
      transporter) and ferroportin in addition to liver ferritin amounts were higher (P
      < 0.05) in the inulin group versus controls. Results indicate that intra-amniotic
      administration and dietary inulin improved the iron status of iron-deficient
      broilers.

PMID- 22582295
TI  - Influence of limestone and phytase on broiler performance, gastrointestinal pH,
      and apparent ileal nutrient digestibility.
AB  - An experiment was conducted to determine the influence of 2 levels of dietary Ca
      from limestone and 3 levels of phytase on broiler performance, bone ash,
      gastrointestinal pH, and apparent ileal digestibility (AID) of Ca, P, and amino
      acids. Cobb 500 broilers (n = 576) were allowed access to one of 6 corn-soy diets
      from 0 to 16 d. Experimental diets contained 1.03% or 0.64% Ca from limestone and
      0.61% total P. Each diet was supplemented with 0, 500, or 5,000 FTU/kg of phytase
      to create a 2 * 3 factorial experiment. Broiler feed intake (FI) and BW gain were
      not affected by dietary Ca or phytase. Feed conversion ratio was improved (P <
      0.05) as dietary phytase increased (1.36, 1.34, and 1.31, respectively). Tibia
      ash percent was reduced (P < 0.05) from 41.4 to 40.0% as dietary Ca decreased but
      increased with phytase addition (P < 0.05). Gizzard and ileal pH were reduced (P
      < 0.05) in broilers fed 0.64% Ca compared with broilers fed 1.03% Ca. Phytase at
      5,000 FTU/kg increased (P < 0.05) pH in the gizzard, duodenum, jejunum, and
      ileum. Apparent ileal P digestibility was increased (P < 0.05) in broilers fed
      0.64% Ca compared with broilers fed 1.03% Ca (0.68 vs. 0.73, respectively).
      Apparent ileal Ca digestibility was increased (P < 0.05) in broilers fed 1.03% Ca
      compared with broilers fed 0.64% Ca (0.67 vs. 0.53, respectively). Phytase
      improved AID of CP in broilers fed 1.0% Ca but did not have an effect on AID of
      CP in broilers fed 0.64% Ca, which resulted in a Ca * phytase interaction (P <
      0.05). In conclusion, high dietary Ca increased pH in gizzard and ileum and
      interfered with the AID of P and CP. The interactions between Ca and phytase in
      the gastrointestinal tract are complex, and feeding phytase at doses above
      industry recommendations may allow for reduced-Ca diets while maintaining broiler
      performance, bone ash, and improving amino acid digestibility.

PMID- 22582296
TI  - Performance, egg quality, and immune response of laying hens fed diets
      supplemented with mannan-oligosaccharide or an essential oil mixture under
      moderate and hot environmental conditions.
AB  - In total, 432 thirty-six-week-old laying hens were fed a basal diet supplemented
      with mannan-oligosaccharide (MOS) or an essential oil mixture (EOM) from 36 to 51
      wk of age. Hens were divided into 3 equal groups replicated 6 times with 24 hens
      per replicate. No significant difference was observed among the dietary
      treatments in terms of performance indices. Different from the dietary
      manipulation, high environmental temperatures negatively influenced all of the
      laying performance traits except the feed conversion ratio in association with
      the diminished feed consumption. The MOS, and particularly the EOM, tended to
      alleviate the deleterious effect of heat stress on BW gain. Mortality was higher
      in MOS-fed hens than with other treatments. A supplementation diet with MOS or
      EOM provided increments in eggshell weight (P < 0.01). Relative albumen weight
      was significantly decreased (P < 0.05) in response to EOM or MOS supplementation;
      however, this was not the case in the yolk weight rate. The MOS decreased albumen
      height and Haugh unit (P < 0.05). High environmental temperatures hampered entire
      egg quality characteristics except for the eggshell breaking strength and egg
      yolk weight. These results indicated that heat stress adversely affected both
      productive performance and egg quality. As for the results of this study, neither
      MOS nor EOM was efficacious in improving efficiency of egg production and
      stimulating humoral immune response in laying hens reared under moderate and hot
      climatic conditions. However, the ameliorative effect exerted by MOS and EOM on
      eggshell characteristics is conclusive.

PMID- 22582298
TI  - Using corn starch as basal diet to determine the true metabolizable energy of
      protein feedstuffs in Chinese Yellow chickens.
AB  - Two experiments were conducted to investigate the feasibility of using corn
      starch as the basal diet to determine the ME of protein feedstuffs using the TME
      assay in Chinese Yellow chickens. In the first experiment, the TME of corn starch
      were determined by force-feeding 25 or 40 g of feed. To test the repeatability of
      the bioassay, the same experiment was repeated 4 times. In the second experiment,
      the TME of soybean meal and cottonseed meal was determined by considering corn
      starch as the basal diet, while corn was fed alone to the chickens. To test the
      accuracy of the TME assay for individual ingredients, the additivity was
      evaluated by determining the TME of 3 mixed diets: corn-soybean meal diet, corn
      cottonseed meal diet, and corn-soybean meal-cottonseed meal diet. In experiment
      1, the value of endogenous energy loss was 16.76 to 18.46 kcal/48 h, and no
      significant differences between the 4 assays were noted. The TME and energy
      metabolizability of the 25-g corn starch treatment (4.06 kcal/g and 98.06%) were
      higher than those of the 40-g treatment (3.79 kcal/g and 91.45%; P < 0.01);
      whereas the CV were less than that of the 40-g treatment, indicating that it is
      reasonable to use the TME value of the 25-g treatment in feed formulation. In
      experiment 2, the TME values for corn, soybean meal, and cottonseed meal were
      4.02, 3.39, and 2.92 kcal/g, respectively. The observed and predicted TME values
      of the corn-soybean meal, corn-cottonseed meal, and corn-soybean meal-cottonseed
      meal diets were in high agreement with differences ranging from -0.02 to 0.01
      kcal/g. None of the differences was significant, indicating an accurate measure
      of the TME of the individual ingredients. Thus, using corn starch as the basal
      diet to determine the TME of protein feedstuffs was validated.

PMID- 22582297
TI  - Effects of a xylanase and protease, individually or in combination, and an
      ionophore coccidiostat on performance, nutrient utilization, and intestinal
      morphology in broiler chickens fed a wheat-soybean meal-based diet.
AB  - The effects of 2 single exogenous and monocomponent feed enzymes, and their
      combination, and an ionophore coccidiostat on production performance, feed
      AME(n), nutrient utilization, and intestinal morphology were studied in broiler
      chickens. One-day-old unvaccinated and unsexed Ross 308 birds (n = 320) were kept
      in groups of 8 on wood shavings in pens raised from the floor and fed one of 5
      experimental diets, replicated 8 times, for 36 d. Treatments were 1) a wheat
      soybean meal-based feed with no added coccidiostats or exogenous enzymes (CON),
      2) CON + ionophore coccidiostat (Narasin), 3) CON + xylanase (Ronozyme WX CT;
      XYL), 4) CON + serine protease (Ronozyme ProAct CT; PRO), or 5) CON + xylanase +
      serine protease (XYL+PRO). Enzymes were added on top in the feed formulation.
      Diets contained 0.5% TiO2 to facilitate estimations of total tract apparent
      nutrient utilization. Treatments had no effect on BW gain or feed intake, but
      feed conversion, apparent digestibility of starch and fat, and feed AME(n) were
      improved with all enzyme treatments. The relative length of the ileum was reduced
      with XYL+PRO. For all parameters measured, the effects of XYL+PRO were similar to
      when XYL and PRO were fed individually. Narasin had no effect on production
      performance or nutrient utilization but reduced the relative lengths of jejunum
      and ileum. Relative lengths and weights of duodenum and cecum were unaffected by
      treatments. In conclusion, the improved feed conversion with both a xylanase and
      a protease was reflected in increased nutrient utilization, but their combination
      was not superior to when supplied separately. Narasin did not affect performance
      or nutrient utilization but reduced the relative lengths of the jejunum and
      ileum.

PMID- 22582299
TI  - Effect of crude protein and fat content of diet on productive performance and egg
      quality traits of brown egg-laying hens with different initial body weight.
AB  - A trial was conducted to study the influence of CP and fat content of the diet on
      performance and egg quality traits of brown egg-laying hens from 22 to 50 wk of
      age. The experiment was conducted as a completely randomized design with 8
      treatments arranged factorially with 4 diets and 2 initial BW of the hens (1,592
      vs. 1,860 g). Three of these diets differed in the CP content (16.5, 17.5, and
      18.5%) and included 1.8% added fat. The fourth diet also had 18.5% CP but was
      supplemented with 3.6% fat instead of 1.8% fat. Each treatment was replicated 4
      times, and the experimental unit consisted of 21 hens allocated into groups of 7
      in 3 adjacent cages. All diets were isocaloric (2,750 kcal of AME/kg) and met the
      recommendations of brown egg-laying hens for digestible Arg, Ile, Lys, Met, Thr,
      Trp, TSAA, and Val. Productive performance and egg quality were recorded by
      replicate every 28 d. For the entire experimental period, diet did not affect any
      of the productive performance traits studied, but the heavier hens had higher
      ADFI (120.6 vs. 113.9 g; P < 0.001), egg production (92.5 vs. 89.8%; P < 0.01),
      and egg weight (64.9 vs. 62.4 g; P < 0.001) than the lighter hens. Initial BW did
      not affect feed conversion per kilogram of eggs or hen mortality, but BW gain was
      higher (289 vs. 233 g; P < 0.01) and feed conversion ratio per dozen of eggs was
      better (1.52 vs. 1.57; P < 0.01) for the lighter than for the heavier hens. None
      of the egg quality variables studied was affected by dietary treatment or initial
      BW of the hens. It is concluded that brown egg-laying hens, irrespective of their
      initial BW, do not need more than 16.5% CP to maximize egg production, provided
      that the diet meets the requirements for key indispensable amino acids. Heavier
      hens produce more eggs that are larger than lighter hens but feed efficiency per
      kilogram of eggs is not affected.

PMID- 22582300
TI  - Effect of snack food by-product inclusion on production of laying hens.
AB  - The increased interest in becoming green for consumers and companies is driving
      groups to develop innovative ways to become more efficient and reduce their
      waste. Foods past their expiration dates are large sources of waste and are
      causing food-manufacturing companies to develop waste disposal strategies.
      Integrating by-products from these companies into animal diets, specifically that
      of laying hens, could be significantly more cost effective for both the human
      food manufacturers and the agricultural producers. The study's objective is to
      evaluate laying hen diets containing snack food by-product, consisting mostly of
      expired potato chips, and the effect on hen performance. In total, 192 White
      Leghorn laying hens (45 wk old) were selected from the Michigan State University
      Poultry Farm. Hens were housed in conventional cages (3 birds/cage) and received
      1 of 4 diets for 5 wk: 1) industry control corn-soybean meal, 2) control with 3%
      by-product, 3) control with 6% by-product, and 4) control with 9% by-product.
      Diets were formulated to be isocaloric, isonitrogenous, and balanced for sodium.
      Feed intake was measured for 3 consecutive days each week, and no overall
      differences between treatments were observed. However, during the first week,
      feed intake was significantly higher in birds fed the 6% and 9% diets compared
      with those fed control (P < 0.05). Birds fed the 6% had a higher feed intake than
      that of the control again during the fourth week (P < 0.01). Egg production, egg
      weight, and specific gravity were measured weekly. Hen BW was measured on d 1,
      14, 28, and 35. Egg production, egg weight, specific gravity, and BW were not
      significantly affected by the addition of snack food by-products to the diet. In
      conclusion, the addition of expired snack food by-product into poultry diets does
      not significantly affect laying hen egg production and has the potential to be
      used as an alternative feed stuff in the future.

PMID- 22582301
TI  - Ultrastructural identification of interstitial cells of Cajal in hen oviduct.
AB  - The interstitial cells of Cajal (ICC) are widely believed to be neuroeffector
      cells of smooth muscle activity in all tubular organs, including the oviduct. The
      avian oviduct involves the secretion, sheathing, and transportation of a large
      sized egg, but there is no information available on ICC in this special organ. We
      have demonstrated the presence of ICC in different segments throughout the
      oviduct in the laying hen and provided details on their ultrastructure by
      transmission electron microscopy technique, for the first time. The observed ICC
      appeared bipolar and multipolar cells of different shapes, with varying nuclear
      morphologies, a thin rim of electron-dense cytoplasm, and an infrequent basal
      lamina. They showed moniliform primary processes with one or 2 secondary or
      terminal processes. We found ICC near smooth muscle cells, nerve fibers, and the
      epithelia, where they make specialized contacts in the form of close membrane
      associations or gap-like junctions and peg-and-socket-like junctions. Intricate
      labyrinthine-type networking contacts were also present in ICC processes.
      Moreover, we report for the first time, that ICC in avian oviduct make
      interdigitating contacts with the epithelium. Cytoplasmic organelles identified
      in ICC include numerous well-developed mitochondria, abundant rough endoplasmic
      reticulum, and dispersed intermediate filaments. Many caveolae and vesicles were
      also present. Golgi bodies and centrioles were rare. Fibroblasts, on the other
      hand, were distinct cells with larger cytoplasmic area, more rough endoplasmic
      reticulum, and less mitochondrial content. No basal lamina, intermediate
      filaments, or caveolae were present in fibroblasts. Their processes were shorter
      and showed no contacts with smooth muscle cells or nerves. We conclude that these
      ICC might also have a key role in the regulatory mechanisms of motility and
      transportation in the hen oviduct, as already proved in mammalian oviduct. Such
      role of ICC might also be responsible for the function of the muscular
      infundibulum, where the fertilization takes place, and that moves to surround the
      released ovum, failure of which results in the internal laying.

PMID- 22582303
TI  - The relationship of parthenogenesis in virgin Chinese Painted quail (Coturnix
      chinensis) hens with embryonic mortality and hatchability following mating.
AB  - Unfertilized chicken, turkey, and quail eggs are capable of developing embryos by
      parthenogenesis. However, it is unknown if the physiological mechanisms
      regulating parthenogenesis in virgin hens may actually work against
      fertilization, embryonic development, and hatchability of eggs from these same
      hens following mating. Additionally, because most parthenogenic development
      closely resembles early embryonic mortality in fertilized eggs during the first 2
      to 3 d of incubation, it is possible that many unhatched eggs classified as
      containing early embryonic mortality may actually be unfertilized eggs that
      contain parthenogens. Therefore, the objective of this study was to examine the
      relationship of parthenogenesis before mating with embryonic development and
      hatchability characteristics after mating. Based upon their ability to produce
      unfertilized eggs that contain parthenogens, 372 virgin Chinese Painted quail
      hens were divided into 7 groups, according to their incidence of parthenogenesis:
      0, 10, 20, 30, 40, 50, and greater than 50% parthenogenesis. Males were then
      placed with these hens so that fertility, embryonic mortality, and hatchability
      could be evaluated for each hen. Hatchability of eggs set, hatchability of
      fertile eggs, and late embryonic mortality declined dramatically as the incidence
      of parthenogenesis increased. On the other hand, early embryonic mortality
      increased as parthenogenesis increased. Fertility was not different across the 7
      parthenogenesis hen groups, perhaps because unfertilized eggs that exhibited
      parthenogenesis resembled and were therefore classified as early embryonic
      mortality. In conclusion, virgin quail hens that exhibit parthenogenesis appear
      to have impaired embryonic development and hatchability following mating.
      Additional sperm-egg interaction and embryonic research is needed to determine if
      a large portion of the early embryonic mortality experienced by mated hens that
      exhibit parthenogenesis as virgin hens is in fact embryonic development in
      unfertilized eggs.

PMID- 22582302
TI  - Differential expression of calcium-regulating genes in heat-stressed turkey
      breast muscle is associated with meat quality.
AB  - Aberrant postmortem Ca(2+)-regulation in the early postmortem period is
      associated with the occurrence of inferior meat quality in turkeys, described as
      pale, soft, and exudative (PSE). The objective of the current study was to
      quantify expression of 4 candidate genes responsible for maintaining Ca(2+)
      homeostasis in turkey skeletal muscle as a function of heat stress: alpha and
      beta ryanodine receptors (RYR; Ca(2+)-release channels), the sarco/endoplasmic
      reticulum Ca(2+)-ATPase 1 (SERCA1), and the sarcoplasmic reticulum, Ca(2+)
      storage protein calsequestrin (CASQ1). Two genetic lines of turkeys were used: a
      growth-selected commercial line and a randombred control line. Market-age birds
      were subjected to one of 5 heat stress treatments: no heat, 1 d, 3 d, 5 d, or 7 d
      of heat followed by 7 d of ambient temperature. Breast muscle samples were
      harvested and classified as normal or PSE using the meat quality parameters
      percentage of marinade uptake and percentage of cook loss. These parameters
      differed significantly by line, heat stress treatment, and meat quality status.
      Expression of candidate genes was measured using TaqMan quantitative PCR. Heat
      treatment was associated with significantly enhanced expression of alphaRYR,
      betaRYR, and CASQ1 in normal muscle from both lines. Conversely, mRNA abundance
      of these genes was reduced in PSE muscle from both lines and recovered or
      increased by 7 d + 7 d of rest. Genetic line differences were observed at several
      time points. Expression of SERCA1 in both normal and PSE samples from both lines
      was unchanged or trended downward with heat stress. Taken together, genetic line
      and heat-stress treatment affected the expression of important Ca(2+)-regulating
      genes in association with meat quality status. The data suggest that birds whose
      meat leads to PSE may fail to respond to heat stress appropriately due to a delay
      in the upregulation of the important calcium-regulating genes: alphaRYR, betaRYR,
      and CASQ1.

PMID- 22582304
TI  - Intrapulmonary arteries respond to serotonin and adenosine triphosphate in
      broiler chickens susceptible to idiopathic pulmonary arterial hypertension.
AB  - This study examined factors contributing to increased vascular resistance and
      plexiform lesion formation in broiler chickens susceptible to idiopathic
      pulmonary arterial hypertension (IPAH). A diet supplemented with excess
      tryptophan (high-Trp diet), the precursor for serotonin, was used to accelerate
      the development of IPAH. Broilers fed the high-Trp diet had higher pulmonary
      arterial pressures than broilers fed the control diet, and plexiform lesion
      incidences tended to be higher (P = 0.11) in the high-Trp group than in the
      control group at 30 d of age. The intrapulmonary arteries were assessed for
      vasoconstriction in response to serotonin and adenosine triphosphate (ATP) and
      for activities of key metabolic enzymes for serotonin and ATP. The pulmonary
      artery (defined as the first major branch of the pulmonary artery inside the
      lung) and the primary pulmonary arterial rami (defined as the second major branch
      of the pulmonary artery inside the lung) both exhibited vasoconstriction in
      response to serotonin and ATP. This is the first study to demonstrate purinergic
      mediated vasoconstriction in intrapulmonary arteries from broilers. Arteriole
      responsiveness did not differ between broilers fed the control diet or the high
      Trp diet. Therefore, the high-Trp diet enhanced the development of IPAH but did
      not affect the artery's sensitivity to serotonin or ATP. Monoamine oxidase
      activity, responsible for the breakdown of serotonin, was severely impaired in
      pulmonary arteries from broilers in the high-Trp group. Accordingly, serotonin
      may persist longer and elicit an amplified response in broilers fed the high-Trp
      diet.

PMID- 22582305
TI  - Regional pulmonary blood flow in the lung of the chicken.
AB  - It is known that alterations in respiratory gases in birds can cause a
      nonhomogenous redistribution of pulmonary blood flow between the 2 separate gas
      exchanging regions of the avian lung, the paleopulmo (PALEO) and neopulmo (NEO);
      however, the effect of alterations in respired gas content on the distribution of
      pulmonary blood flow in birds, such as the chicken, that possess a highly
      developed NEO is not known. This study used a colorimetric microsphere method to
      determine the effects of hypoxia and hypercapnia on the relative distribution of
      pulmonary blood flow in anesthetized chickens (Gallus domesticus) during control
      (normoxic) and experimental (hypoxic or hypercapnic) conditions, where the
      relative regional distribution of blood flow in the lung is expressed as the
      ratio NEO/PALEO. Administration of a hypoxic gas mixture (16.0% O(2)) produced a
      13.4% increase in NEO/PALEO, and, administration of a hypercapnic gas mixture
      (5.0% CO(2)) resulted in a 27.8% increase in NEO/PALEO. Our results are
      consistent with a mechanism in which the regional redistribution of pulmonary
      blood flow is mediated by local intrapulmonary factors.

PMID- 22582306
TI  - Maximizing carbon dioxide content of shell eggs by rapid cooling treatment and
      its effect on shell egg quality.
AB  - Rapid cooling of shell eggs using liquid CO2 has been shown to cool eggs to 7
      degrees C within minutes, as opposed to days required by traditional cooling
      treatments. This quick-cooling technique is component in the maintenance of egg
      quality and extended shelf life beyond the current 30- to 45-d period. The
      hypothesis for the current study was that maximizing CO2 content of the eggs
      during cooling may increase Haugh units and thus extend shelf life (physical
      quality factors). The objective of this study was to maximize CO2 content of
      shell eggs during rapid cooling with liquid CO2 and determine its effect on egg
      quality during 12 wk of refrigerated storage. Three cooling conditions selected
      for the study were -45 degrees C for 18 min (treatment A), -60 degrees C for 15
      min (treatment B), and -75 degrees C for 12 min (treatment C). After rapid
      cooling treatment, it took approximately 25 min for the internal temperature of
      eggs to equilibrate to 7 degrees C. The Haugh units of the rapidly cooled eggs
      were significantly higher than the traditionally cooled (control) eggs. After 12
      wk of refrigerated (5-7 degrees C) storage, control eggs were only 37% AA-grade,
      57% A-grade, and 6% B-grade. In comparison, all the rapidly cooled eggs averaged
      to 80% AA-grade and 20% A-grade. After 6 wk, the average quality of control eggs
      reduced to grade A, whereas rapid cooling treatment was able to maintain AA
      quality up to 12 wk. The CO2 content of the rapidly cooled eggs (1.8 mg of CO2/g
      of albumen) showed no difference between treatments A, B, and C, but it was
      significantly higher than the control (1.3 mg of CO2/g of albumen). In addition,
      the vitelline membrane strength of the control decreased 65% during storage and
      was between 30 and 50% of the vitelline membrane strength of CO2-cooled eggs at
      12 wk. Rapid cooling with liquid CO2 extends shelf life of shell eggs.

PMID- 22582307
TI  - Broiler chicken thigh and breast muscle responses to cold stress during simulated
      transport before slaughter.
AB  - The effect of acute cold exposure was assessed on broiler physiology, breast and
      thigh muscle metabolites, and meat quality. In total, 160 male birds at ages of 5
      and 6 wk were exposed to temperatures of -9 to -15 degrees C (cold stressed) and
      +20 degrees C (control) in a simulated transport chamber for 3 h before slaughter
      followed by 0 or 2 h of lairage. Bird physiology parameters, including core body
      temperature, live shrink, blood glucose, and muscle temperature, were assessed.
      Core body temperature was monitored every minute using i-Button data loggers, and
      live shrink and blood glucose were assessed. Total glucose and lactate
      concentrations at 30 h postmortem, as well as ultimate pH (pH(u)), color, and
      water-holding attributes were evaluated on pectoralis major muscle of breast and
      iliotibialis muscle of thigh. Birds were grouped based on their microclimate
      temperature to control and cold-stressed groups (0 to -8, -8 to -11, and -11 to 
      14 degrees C). Significant (P < 0.05) decreases in core body temperature and
      breast and thigh muscle temperatures were observed at simulated transport
      temperatures below 0 degrees C. In addition, higher (P < 0.05) live shrink and
      lower blood glucose values were observed as a result of 3-h exposure to
      temperatures below 0 degrees C, exacerbated as temperature decreased further
      below -8 degrees C. Thigh muscle was almost depleted of glycogen reserve compared
      with a significant but small reduction in breast muscle glycogen when exposure
      temperature was below -8 degrees C. Similarly, much greater effects were observed
      on thigh pH(u) and quality attributes compared with breast. In addition, 84%
      incidence of the dark, firm, dry quality defect was observed in thigh meat (pH(u)
      > 6.4, L* < 44) compared with 42% incidence of dark, firm, dry in breast meat
      (pH(u) > 6.1, L* < 46) when transportation temperature was below 0 degrees C.
      Results of this study showed that thigh muscle was affected more severely than
      breast muscle by exposure to cold temperatures before slaughter.

PMID- 22582308
TI  - Biogenic amine formation in turkey meat under modified atmosphere packaging with
      extended shelf life: Index of freshness.
AB  - The aim of this study was to evaluate the effect of modified atmosphere packaging
      (MAP) on biogenic amine production in turkey meat according to its shelf life
      period, determining an index of freshness. Sliced meat samples of different meat
      quality categories (according to color and pH24) were individually packaged under
      aerobiosis (aerobic package) and in 6 different modified atmospheres containing
      different gas mixtures: MAP1, 50% N2/50% CO2; MAP2, 0.5% CO/50% CO2/49.5% N2;
      MAP3, 50% Ar/50% N2; MAP4, 0.5% CO/80% CO2/19.5% N2; MAP5, 100% N2; and MAP6, 50%
      Ar/50% CO2. All samples were stored at 0 +/- 1 degrees C in the dark for between
      12 and 25 d. Meat samples packaged in aerobic packaging were analyzed for their
      microbial and physicochemical characteristics on d 0, 5, and 12 of storage, and
      then extended to 19 and 25 d when samples were under MAP. The production of
      biogenic amines analyzed in turkey meat increased over time. The values of
      putrescine, cadaverine, and tyramine increased significantly (P < 0.05) during
      storage time in samples packaged under aerobiosis, MAP3, and MAP5. Histamine was
      not detected in turkey meat packaged under study conditions, or when present, the
      levels were below the limit of quantification (1.03 mg/kg). Tyramine in turkey
      meat under MAP was not the best amine indicator of meat deterioration, with
      cadaverine being suggested instead, or the sum of the amines putrescine,
      cadaverine, and tyramine, to characterize and quantify meat freshness. After 25 d
      of storage, the meat packaged under MAP with a mixture containing a higher
      concentration of CO2 and with CO was the one with a lower index value (11.36
      mg/kg), although not significantly different from the indices provided by the
      meat packaged with MAP1, 2, and 6.

PMID- 22582309
TI  - The effect of sodium lactate and lactic acid combinations on the microbial,
      sensory, and chemical attributes of marinated chicken thigh.
AB  - The present study was undertaken to evaluate the chemical, microbiological, and
      sensory effects of different sodium lactate (SL) and lactic acid (LA)
      combinations on marinated chicken thigh. The latter were treated with SL and LA
      combined at various concentrations, namely 0.3 and 0.03; 0.5 and 0.05; 0.6 and
      0.06; 0.75 and 0.075; and 0.9 and 0.09%, respectively. The findings indicated
      that those combinations were efficient (P < 0.05) against the proliferation of
      various spoilage microorganisms, including aerobic plate count, psychrotrophic
      populations, Pseudomonas spp., Staphylococcus aureus, Enterobacteriaceae, and
      Salmonella spp. The results from chemical analyses revealed that the treated
      thigh underwent significant decreases (P < 0.05) in terms of pH values and total
      volatile base nitrogen contents. Significant differences (P < 0.05) were,
      however, detected with regard to their sensory attributes, with SL-LA
      concentrations of 0.9 and 0.09 yielding the highest scores for the color,
      texture, and flavor attributes. Overall, the findings demonstrated that the
      addition of 0.9% SL and 0.09% LA to marinated chicken can help delay the
      proliferation of spoilage microorganisms, prevent the generation of undesirable
      chemicals, improve the levels of sensory attributes, and extend the shelf life of
      products during refrigerated storage.

PMID- 22582310
TI  - A modified Weibull model for growth and survival of Listeria innocua and
      Salmonella Typhimurium in chicken breasts during refrigerated and frozen storage.
AB  - The potential of food-borne pathogens to survive and grow during refrigerated and
      frozen storage has raised serious concerns over the safety of stored poultry
      products. In this study, the effect of refrigeration and freezing temperatures (
      20, -12, 0, 4, and 8 degrees C) on growth and survival of Listeria innocua and
      Salmonella enterica serovar Typhimurium in raw chicken breasts for storage times
      of 3, 7, 10, 14, and 21 d were investigated. A modified Weibull model was also
      developed to analyze the microbial behavior of both microorganisms in raw chicken
      breasts under different refrigerated storage conditions over time. The results
      showed that the bacterial loads of L. innocua at 4 and 8 degrees C and Salmonella
      Typhimurium at 8 degrees C were significantly different (P < 0.05) from those at
      other refrigerated and frozen storage temperatures over storage times. The loads
      of both bacteria at frozen storage temperatures did not change significantly over
      time. At a storage time of 7 d, the increase in bacterial loads of L. innocua at
      4 and 8 degrees C was 2.1 log cfu/g and 3.7 log cfu/g, respectively, and that of
      Salmonella Typhimurium at 8 degrees C was 1.2 log cfu/g. The root mean square
      errors, median relative error, mean absolute relative error, and the plot of
      predicted versus observed bacterial loads showed a good performance of the model.
      The results from this study provided useful information regarding the behavior of
      Listeria and Salmonella in raw chicken breast meat during refrigerated and frozen
      storage, which would be helpful in giving insight over the safety of poultry
      products storage.

PMID- 22582311
TI  - Meat quality and sensory attributes of a conventional and a Label Rouge-type
      broiler strain obtained at retail.
AB  - Some consumers have reported preferences for meat from alternative broiler
      strains as compared with meat from conventional broiler strains relative to taste
      and texture, but relatively few objective measurements have been conducted on
      these particular strains. To directly compare meat quality from a Label Rouge
      type alternative and a conventional broiler strain available at retail, 4 ready
      to-cook conventional and 6 alternative strain carcasses were obtained from retail
      or a processing plant on each of 6 d. Boneless skinless breast fillets and
      boneless thighs were taken from each carcass and weighed. Raw meat was then
      assigned to different testing lots for cooking to evaluate yield, objective
      texture, meat color, sensory profile, and proximate composition (percentage
      protein, moisture, fat, and ash). Analyses of data revealed no significant
      difference (P < 0.05) due to broiler strain for percentage protein, moisture,
      fat, and ash, for either breast or thigh meat. Conventional breast (raw and
      cooked) weights were significantly higher than the alternative strain, but there
      was no difference in cooked yield. There were no differences between strain for
      thigh weights or yield. Both thigh and breast meat from the conventional broilers
      was more tender than meat from alternative broilers. Cooked conventional breast
      meat was darker and yellower, whereas cooked thigh was lighter, less red, and
      more yellow than alternative meat. Sensory analysis found no difference between
      strains for breast meat attributes. Conventional thigh meat scored higher than
      alternative for appearance, tenderness, juiciness, and how well the panelist
      liked the appearance, but there was no difference in aftertaste or overall
      liking. Although minimal differences were observed for cooked breast meat due to
      strain, conventional cooked thigh meat scored higher than the thigh meat from the
      Label Rouge-type alternative for most of the sensory attributes.

PMID- 22582314
TI  - The association between depression and leptin is mediated by adiposity.
AB  - OBJECTIVE: Animal models suggest that impaired leptin production, or leptin
      resistance despite increased leptin levels, may contribute to depression. The
      link between leptin and depression could be mediated by obesity, which is more
      common in depression and increases leptin production. METHODS: We administered
      the Beck Depression Inventory-II (BDI-II) to 537 participants (mean [standard
      deviation (SD)] age = 51 [9] years; female, 61%) enrolled in the Morehouse and
      Emory Team up to Eliminate Health Disparities (META-Health) study. Leptin levels
      were examined as continuous log-transformed values. RESULTS: Participants with
      moderate to severe depression had higher levels of leptin (median [interquartile
      range] 37.7 [17.6-64.9] ng/mL) than those with mild depression (22.9 [7.0-57.9]
      ng/mL) or minimal to no depression (19.8 ng/mL [7.8-39.1], p = .003).
      Participants with moderate to severe depression had higher body mass index (BMI)
      than those with mild or minimal depression (mean [SD] = 33 [8] versus 31 [9]
      versus 29 [7] kg/m(2), p = .001). After multivariate adjustment for age, sex,
      race, smoking status, hypertension, diabetes, blood pressure, lipids, and C
      reactive protein, the BDI-II score remained a significant predictor of leptin
      levels (beta = 0.093, p = .01). Further adjustment for BMI eliminated the
      association between the BDI-II score and leptin (beta = 0.03, p = .3). Adjusting
      for waist circumference in place of BMI revealed similar findings. CONCLUSIONS:
      The association between depression and leptin seems to be mediated by increased
      adiposity in depressed individuals.

PMID- 22582313
TI  - Individual and neighborhood socioeconomic status and inflammation in Mexican
      American women: what is the role of obesity?
AB  - OBJECTIVE: Inflammation may represent a biological mechanism underlying
      associations of socioeconomic status (SES) with cardiovascular disease. We
      examined relationships of individual and neighborhood SES with inflammatory
      markers in Mexican American women and evaluated contributions of obesity and
      related heath behaviors to these associations. METHODS: Two hundred eighty-four
      Mexican American women (mean age = 49.74 years) were recruited from
      socioeconomically diverse South San Diego communities. Women completed measures
      of sociodemographic characteristics and health behaviors, and underwent a
      physical examination with fasting blood draw for assay of plasma C-reactive
      protein (CRP), interleukin 6 (IL-6), and soluble intercellular adhesion molecule
      1 (sICAM-1). Neighborhood SES was extracted from the US Census Bureau 2000
      database. RESULTS: In multilevel models, a 1-standard deviation higher individual
      or neighborhood SES related to a 27.35% and 23.56% lower CRP level (p values <
      .01), a 7.04% and 5.32% lower sICAM-1 level (p values < .05), and a 10.46% (p <
      .05) and 2.40% lower IL-6 level (not significant), respectively. Controlling for
      individual SES, a 1-standard deviation higher neighborhood SES related to a
      18.05% lower CRP level (p = .07). Differences in body mass index, waist
      circumference, and dietary fat consumption contributed significantly to SES
      inflammation associations. CONCLUSIONS: The findings support a link between SES
      and inflammatory markers in Mexican American women and implicate obesity and
      dietary fat in these associations. Additional effects of neighborhood SES were
      not statistically significant; however, these findings should be viewed
      tentatively due to the small sample size to evaluate contextual effects. Trial
      Registration ClinicalTrials.gov identifier: NCT00387166.

PMID- 22582315
TI  - Introduction: Is there a nonverbal period of development?

PMID- 22582316
TI  - Why this question? Commentary on Vivona.

PMID- 22582317
TI  - Is there language disconnected from sensory/bodily experience in speech or
      thought? Commentary on Vivona.

PMID- 22582318
TI  - Does it matter if there is a nonverbal period of development? On the infant's
      understanding the social world and its implications for psychoanalytic therapy.

PMID- 22582319
TI  - More meaning: commentary on Vivona.

PMID- 22582322
TI  - Will patients accept randomization to psychoanalysis? A feasibility study.
AB  - The feasibility of using a randomized design in a psychoanalytic outcome study
      was evaluated. Our hypothesis was that it would be feasible to randomize patients
      to psychoanalysis three or four times weekly on the couch for five years,
      supportive expressive therapy once or twice weekly for up to forty sessions, and
      cognitive behavior therapy once or twice weekly for up to forty sessions.
      Successful randomization was defined as a 30% recruitment rate among eligible
      patients. Recruitment began in September 2009 and closed in April 2010. A total
      of 132 subjects responded to study advertisements, 107 of whom (81%) were triaged
      out. The remaining 25 were scheduled for the first of two clinical interviews,
      and 21 of 25 (88%) completed the interview. Eleven of the 25 (44%) were
      determined to be eligible based on inclusion and exclusion criteria. Eight of the
      11 accepted the idea of randomization and completed the diagnostic assessment
      phase. Calculated on the basis of 8 of 11 eligible patients accepting
      randomization, the 95% confidence interval was that 39% to 92% of eligible
      subjects would participate in a larger study of this design. Our findings support
      the feasibility of implementing an RCT comparing psychoanalysis as defined by the
      American Psychoanalytic Association (three or four times weekly on the couch for
      approximately five years) with shorter-term dynamic or cognitive behavioral
      therapy once or twice a week. Pre-treatment characteristics of these eight
      patients are presented, as are initial reliability data for the treatment
      adherence scales used in this trial.

PMID- 22582321
TI  - The development of a psychoanalytic outcome study: choices, conflicts, and
      consensus.
AB  - This article tells the story of the development of an outcome study of
      psychoanalysis and describes the debate that took place over critical
      methodological issues. The protocol committee included career psychotherapy
      researchers who have conducted rigorous outcome studies, clinical psychoanalysts,
      study methodologists, and a statistician with clinical trial expertise. The
      committee worked for two years to develop the study design. This project is based
      on the premise that clinical psychoanalysis is a treatment. Areas specifically
      addressed are the goals and hypothesis of the study, inclusion and exclusion
      criteria, choice of psychotherapies as comparison treatments, definition of
      treatments and selection of therapists, use of medication, development of a
      treatment adherence measure, randomization of patient assignment vs. patient self
      selection, and primary outcome measures. The execution of this outcome study will
      require significant effort and resources. A positive result would boost the
      standing of psychoanalysis, but the results may not support the primary
      hypothesis that there are therapeutic benefits unique to psychoanalysis and that
      psychoanalysis can effect demonstrable changes in a patient's mental life and
      adaptation that are not achieved by treatments of different orientation and/or
      lesser intensity. However, more important than whatever specific results emerge
      is what executing such a study requires of our field: the process of addressing
      the clinical issues that a study design requires, the creation of a network of
      analysts around the country working on a common project, and the joining of the
      clinical psychoanalytic community with a community of psychodynamic researchers.

PMID- 22582323
TI  - Designs for studying the effectiveness of long-term psychoanalytic treatments:
      balancing level of evidence and acceptability to patients.
AB  - Long-Term Psychoanalytic Treatments (LTPT) include both long-term psychoanalytic
      psychotherapy (LTPP) and psychoanalysis (PsAn). Current opinion seems to be that
      there is some evidence for the effectiveness of LTPP, but none for that of PsAn.
      This may be due in part to researchers not balancing the level of evidence of
      randomized controlled studies (RCTs), cohort studies, and pre-post studies with
      patients' acceptance of these various research designs used in studying the
      effectiveness of LTPT. After a review of the merits of eight possible control
      conditions for LTPT in RCTs and cohort studies, and a consideration of the
      limitations and merits of pre-post studies, it was found that RCTs pair high
      levels of evidence with limited degrees of patient acceptance, especially where
      PsAn is concerned. Cohort studies appear to provide at most a moderate level of
      evidence. Their acceptability is hardly better than that of RCTs, as it depends
      on the acceptability of control conditions similar to those of RCTs. The
      acceptability of pre-post studies is much better, but they can provide, at most,
      a moderate level of evidence. Apart from randomization, they can meet all
      methodological criteria for high-quality research (often they do not, but there
      are ways to correct this). In summary, in the long-term treatment of complex
      mental disorders with LTPT, RCTs often pair a high level of evidence with limited
      patient acceptance of the method. Compared to RCTs, cohort studies show a lower
      level of evidence without much gain in acceptability. Pre-post studies pair the
      highest level of acceptability with the lowest level of evidence of the three
      designs. Limited acceptability is not to be confused with no acceptability, nor
      moderate level of evidence with none.

PMID- 22582325
TI  - Nina Coltart: her life and work.

PMID- 22582326
TI  - Effects of peer-mediated implementation of visual scripts in middle school.
AB  - Although research has investigated the impact of peer-mediated interventions and
      visual scripts on social and communication skills in children with autism
      spectrum disorders, no studies to date have investigated peer-mediated
      implementation of scripts. This study investigated the effects of peer
      implemented scripts on a middle school student with autism, intellectual
      impairments, and speech-language impairment via a multiple baseline single-case
      research design across behaviors. The target student demonstrated improvements in
      three communicative behaviors when implemented by a trained peer; however,
      behaviors did not generalize to use with an untrained typically developing peer.

PMID- 22582327
TI  - Bed-sharing influences, attitudes, and practices: implications for promoting safe
      infant sleep.
AB  - The purpose of this study was to examine the infant bed-sharing practices of
      mothers from the birth of the infant to three months of age. The study was a
      longitudinal descriptive design using a self-report instrument immediately after
      delivery with follow-up phone interviews at one and three months after discharge.
      While no mothers intended to bed-share with their infants immediately after
      delivery, 60 percent reported bed-sharing at some time at one month after
      discharge and 9 percent at three months. Only 19 percent of mothers reported
      receiving information about infant sleeping practices from their physician and 22
      percent from their nurse. One month post discharge was identified as a high-risk
      period for infant bed-sharing. Interventions aimed at teaching new mothers about
      responding to infant cues and ways to manage a fussy infant may minimize the rate
      of bed-sharing.

PMID- 22582328
TI  - Position paper: proposal for a core curriculum for a European Sports Cardiology
      qualification.
AB  - Sports cardiology is a new and rapidly evolving subspecialty. It aims to
      elucidate the cardiovascular effects of regular exercise and delineate its
      benefits and risks, so that safe guidance can be provided to all individuals
      engaging in sports and/or physical activity in order to attain the maximum
      potential benefit at the lowest possible risk. The European Society of Cardiology
      (ESC) advocates systematic preparticipation cardiovascular screening in an effort
      to identify competitive athletes at risk of exercise-related cardiovascular
      events and sudden cardiac death. However, the implementation of preparticipation
      screening is hindered because of lack of structured training and as a result lack
      of sufficient expertise in the field of sports cardiology. In 2008 the European
      Society of Cardiology published a core curriculum for the general cardiologist,
      in which sports cardiology was incorporated within the topic 'Rehabilitation and
      Exercise Physiology'. However, the exponential rise in knowledge and the growing
      demand for expertise in the field of sports cardiology dictates the need to
      systematically structure the knowledge base of sports cardiology into a detailed
      curriculum. We envisage that the curriculum would facilitate more uniform
      training and guideline implementation throughout Europe, and safeguard that
      evaluation and guidance of competitive athletes or individuals who wish to engage
      in leisure-time sports activities is performed by physicians with expertise in
      the field. The current manuscript provides a comprehensive curriculum for sports
      cardiology, which may serve as a framework upon which universities and national
      and international health authorities will develop the training, evaluation and
      accreditation in sports cardiology. 

PMID- 22582329
TI  - Ambulatory monitoring of biobehavioral processes in health and disease.

PMID- 22582331
TI  - Computerized adaptive testing--ready for ambulatory monitoring?
AB  - BACKGROUND: Computerized adaptive tests (CATs) have abundant theoretical
      advantages over established static instruments, which could improve ambulatory
      monitoring of patient-reported outcomes (PROs). However, an empirical
      demonstration of their practical benefits is warranted. METHODS: We reviewed the
      literature and evaluated existing data to discuss the potential of CATs for use
      in ambulatory monitoring outside clinical facilities. RESULTS: Computerized
      adaptive tests are not being used for ambulatory monitoring, but initial results
      from their use in health care research allow for discussion of some issues
      relevant to ambulatory care. Evidence shows that CATs can capture the most
      relevant health outcomes as well as established static tools, with substantially
      decreased respondent burden. They can be more precise than static tools of
      similar length and can reduce floor and ceiling effects. Computerized adaptive
      tests can reliably measure a construct over time with different items, which
      yields the potential of introducing item exposure control in ambulatory
      monitoring. Studies have shown that CATs can be at least as valid as well
      designed static tools in group comparisons, but further investigation is needed
      to determine whether psychometric advantages lead to increased responsiveness of
      CATs. CONCLUSIONS: Ambulatory monitoring of PROs demands short, yet very precise
      measurements, which can be repeated up to many times a day. Computerized adaptive
      tests may address several present shortcomings in ambulatory monitoring of PROs
      efficiently. However, most CAT developments have primarily focused on
      psychometric improvements. To use the full potential of CATs for ambulatory
      monitoring purposes, content must also be carefully considered.

PMID- 22582330
TI  - Trends in ambulatory self-report: the role of momentary experience in
      psychosomatic medicine.
AB  - In this article, we review the differences between momentary, retrospective, and
      trait self-report techniques and discuss the unique role that ambulatory reports
      of momentary experience play in psychosomatic medicine. After a brief historical
      review of self-report techniques, we discuss the latest perspective that links
      ambulatory self-reports to a qualitatively different conscious self-the
      "experiencing self"--which is functionally and neuroanatomically different from
      the "remembering" and "believing" selves measured through retrospective and trait
      questionnaires. The experiencing self functions to navigate current environments
      and is relatively more tied to the salience network and corporeal information
      from the body that regulates autonomic processes. As evidence, we review research
      showing that experiences measured through ambulatory assessment have stronger
      associations with cardiovascular reactivity, cortisol response, immune system
      function, and threat/reward biomarkers compared with memories or beliefs. By
      contrast, memories and beliefs play important roles in decision making and long
      term planning, but they are less tied to bodily processes and more tied to
      default/long-term memory networks, which minimizes their sensitivity for certain
      research questions. We conclude with specific recommendations for using self
      report questionnaires in psychosomatic medicine and suggest that intensive
      ambulatory assessment of experiences may provide greater sensitivity for
      connecting psychological with biologic processes.

PMID- 22582332
TI  - Ambulatory monitoring in the genetics of psychosomatic medicine.
AB  - Psychosomatic disorders are composed of an array of psychological, biologic, and
      environmental features. The existing evidence points to a role for genetic
      factors in explaining individual differences in the development and maintenance
      of a variety of disorders, but studies to date have not shown consistent and
      replicable effects. As such, the attempt to uncover individual differences in the
      expression of psychosomatic disorders as a function of genetic architecture
      requires careful attention to their phenotypic architecture or the various
      intermediate phenotypes that make up a heterogeneous disorder. Ambulatory
      monitoring offers a novel approach to measuring time-variant and situation
      dependent intermediate phenotypes. Recent examples of the use of ambulatory
      monitoring in genetic studies of stress reactivity, chronic pain, alcohol use
      disorders, and psychosocial resilience are reviewed in an effort to highlight the
      benefits of ambulatory monitoring for genetic study designs.

PMID- 22582334
TI  - Exploring dynamics in mood regulation--mixture latent Markov modeling of
      ambulatory assessment data.
AB  - OBJECTIVE: To illustrate how fluctuation patterns in ambulatory assessment data
      with features such as few categorical items, measurement error, and heterogeneity
      in the change pattern can adequately be analyzed with mixture latent Markov
      models. The identification of fluctuation patterns can be of great value to
      psychosomatic research concerned with dysfunctional behavior or cognitions, such
      as addictive behavior or noncompliance. In our application, unobserved subgroups
      of individuals who differ with regard to their mood regulation processes, such as
      mood maintenance and mood repair, are identified. METHODS: In an ambulatory
      assessment study, mood ratings were collected 56 times during 1 week from 164
      students. The pleasant-unpleasant mood dimension was assessed by the two ordered
      categorical items unwell-well and bad-good. Mixture latent Markov models with
      different number of states, classes, and degrees of invariance were tested, and
      the best model according to information criteria was interpreted. RESULTS: Two
      latent classes that differed in their mood regulation pattern during the day were
      identified. Mean classification probabilities were high (>0.88) for this model.
      The larger class showed a tendency to stay in and return to a moderately pleasant
      mood state, whereas the smaller class was more likely to move to a very pleasant
      mood state and to stay there with a higher probability. CONCLUSIONS: Mixture
      latent Markov models are suitable to obtain information about interindividual
      differences in stability and change in ambulatory assessment data. Identified
      mood regulation patterns can serve as reference for typical mood fluctuation in
      healthy young adults.

PMID- 22582333
TI  - Continuous glucose monitoring: a review for behavioral researchers.
AB  - OBJECTIVE: Continuous glucose monitoring (CGM) systems collect and store glucose
      data in an ongoing fashion for several days at a time. The main advantage of CGM
      is that it can help identify fluctuations and trends that would otherwise go
      unnoticed with other glucose measures. Here, we provide a review of CGM for
      behavioral researchers. METHODS: We begin with a brief review of diabetes and
      glucose measurement and then describe what CGM is and reference the commercial
      CGM systems currently available. We discuss the challenges involved in using CGM
      in behavioral research. We then present a broad overview of CGM in behavioral
      research, including data from ours and others' research programs. Finally, we
      cover some practical issues to be considered when using CGM, suggest reporting
      guidelines for the behavioral researcher, and offer suggestions for future
      research. RESULTS: Only a handful of behavioral researchers are using CGM,
      although its use is increasing. The main ways that CGM is being used in
      behavioral research is to investigate basic biobehavioral processes, to assess
      the effects of behavioral interventions on diabetes control, and to use CGM
      itself as a behavior modification and teaching tool in diabetes self-management
      interventions. CONCLUSIONS: Continuous glucose monitoring holds promise to help
      behavioral researchers unravel the complex relationships among glucose and
      intrapersonal, interpersonal, and contextual factors. However, the uptake of CGM
      for this purpose is limited, and the possibilities for its use are largely unmet.
      We encourage behavioral researchers to implement CGM in their protocols and to do
      so in a way that maximizes its explanatory power.

PMID- 22582335
TI  - Revealing causal heterogeneity using time series analysis of ambulatory
      assessments: application to the association between depression and physical
      activity after myocardial infarction.
AB  - OBJECTIVE: Studies in psychosomatic medicine are characterized by analyses that
      typically compare groups. This nomothetic approach leads to conclusions that
      apply to the average group member but not necessarily to individual patients.
      Idiographic studies start at the individual patient and are suitable to study
      associations that differ between time points or between individuals. We
      illustrate the advantages of the idiographic approach in analyzing ambulatory
      assessments, taking the association between depression and physical activity
      after myocardial infarction as an example. METHODS: Five middle-aged men who had
      myocardial infarction with mild to moderate symptoms of depression were included
      in this study. Four of these participants monitored their physical activity and
      depressive symptoms during a period of 2 to 3 months using a daily self
      registration form. The time series of each individual participant were
      investigated using vector autoregressive modeling, which enables the analysis of
      temporal dynamics between physical activity and depression. RESULTS: We found
      causal heterogeneity in the association between depression and physical activity.
      Participants differed in the predominant direction of effect, which was either
      from physical activity to depression (n = 1, 85 observations, unstandardized
      effect size = -0.183, p = .03) or from depression to physical activity (n = 2, 65
      and 59 observations, unstandardized effect sizes = -0.038 and -0.381, p < .001
      and p = .04). Also, the persistency of effects differed among individuals.
      CONCLUSIONS: Vector autoregressive models are suitable in revealing causal
      heterogeneity and can be easily used to analyze ambulatory assessments. We
      suggest that these models might bridge the gap between science and clinical
      practice by translating epidemiological results to individual patients.

PMID- 22582336
TI  - Expanding options for developing outcome measures from momentary assessment data.
AB  - OBJECTIVE: We propose several different patient-reported outcomes (PROs) from
      momentary, real-time collection of symptom data. In addition to the mean of
      momentary reports of symptoms, other types of summaries can reflect different
      aspects of the symptom experience. METHODS: With secondary analyses of two
      studies of patients with chronic pain assessed with real-time methods, we
      demonstrate principles for developing outcomes that summarize symptom experience
      during a 1-week period. These studies focused on pain intensity, which is used to
      demonstrate methods for creating summary momentary measures. RESULTS: Analyses
      from the first study (Pain 2008;139:146-57) yielded outcome measures based on the
      mean, median, 90th percentile, maximum, standard deviation, proportion of reports
      with no pain, proportion of reports with pain more than 50 (on a 0- to 100-point
      scale), and time-contingent measures. The second study examined the performance
      of these measures (and the mean) in a longitudinal study, in which some patients
      changed treatment (n = 78), making pain reduction likely, whereas others had no
      treatment change (n = 27). The measure that best discriminated the groups was the
      proportion of momentary reports without pain (effect size = 0.50), closely
      followed by the mean of all reports (effect size = 0.45). Most measures also
      correlated with patients' global impression of their change (between 0.39 and
      0.55, except for standard deviation [0.13]). CONCLUSIONS: These analyses suggest
      that momentary symptom data can be useful for developing new PROs that reflect
      symptom experience other than the mean. They highlight knowledge gleaned from
      real-time studies, which deepens our understanding of symptoms by demonstrating
      which changes in symptoms are associated with overall perceived change.

PMID- 22582337
TI  - Close relationships and health in daily life: a review and empirical data on
      intimacy and somatic symptoms.
AB  - OBJECTIVE: To review research on close relationships and health in daily life,
      with a focus on physiological functioning and somatic symptoms, and to present
      data on the within-person effects of physical intimacy on somatic symptoms in
      committed couples' daily life. The empirical study tested whether prior change in
      physical intimacy predicted subsequent change in symptoms, over and above their
      concurrent association. In addition, the study tested if increasing and
      decreasing intimacy had asymmetric effects on symptom change. METHODS: In this
      study, 164 participants in 82 committed couples reported physical intimacy and
      somatic symptoms once a day for 33 days. RESULTS: Prior within-person change in
      intimacy predicted a subsequent reduction in symptoms; when a person's intimacy
      increased from one day to the next day, then symptoms decreased over the
      following days (B = -0.098, standard error [SE] = 0.038, p = .013). This lagged
      effect of intimacy held over and above the association of concurrent change in
      intimacy and symptoms (B = -0.122, SE = 0.041, p = .004). The study found
      asymmetric effects of prior increase and decrease in intimacy; prior intimacy
      increase predicted reduced subsequent symptoms (B = -0.189, SE = 0.068, p =
      .047), whereas prior intimacy decrease was unrelated to subsequent symptoms (B = 
      0.003, SE = 0.063, not significant). There was no evidence for asymmetric effects
      of intimacy increase and decrease on concurrent symptom change. CONCLUSIONS:
      Close relationships exert influences on health in daily life, and part of this
      influence is due to intimacy.

PMID- 22582338
TI  - Naturalistic observation of health-relevant social processes: the electronically
      activated recorder methodology in psychosomatics.
AB  - This article introduces a novel observational ambulatory monitoring method called
      the electronically activated recorder (EAR). The EAR is a digital audio recorder
      that runs on a handheld computer and periodically and unobtrusively records
      snippets of ambient sounds from participants' momentary environments. In tracking
      moment-to-moment ambient sounds, it yields acoustic logs of people's days as they
      naturally unfold. In sampling only a fraction of the time, it protects
      participants' privacy and makes large observational studies feasible. As a
      naturalistic observation method, it provides an observer's account of daily life
      and is optimized for the objective assessment of audible aspects of social
      environments, behaviors, and interactions (e.g., habitual preferences for social
      settings, idiosyncratic interaction styles, subtle emotional expressions). This
      article discusses the EAR method conceptually and methodologically, reviews prior
      research with it, and identifies three concrete ways in which it can enrich
      psychosomatic research. Specifically, it can (a) calibrate psychosocial effects
      on health against frequencies of real-world behavior; (b) provide ecological
      observational measures of health-related social processes that are independent of
      self-report; and (c) help with the assessment of subtle and habitual social
      behaviors that evade self-report but have important health implications. An
      important avenue for future research lies in merging traditional self-report
      based ambulatory monitoring methods with observational approaches such as the EAR
      to allow for the simultaneous yet methodologically independent assessment of
      inner, experiential aspects (e.g., loneliness) and outer, observable aspects
      (e.g., social isolation) of real-world social processes to reveal their unique
      effects on health.

PMID- 22582339
TI  - Salivary cortisol in ambulatory assessment--some dos, some don'ts, and some open
      questions.
AB  - The impact of stress on health and disease is an important research topic in
      psychosomatic medicine. Because research on hypothalamic-pituitary-adrenal (HPA)
      axis regulation under controlled laboratory studies lacks ecological validity, it
      needs to be complemented by a research program that includes momentary ambulatory
      assessment. The measurement of salivary cortisol offers the possibility to trace
      the free steroid hormone concentrations in ambulant settings. Therefore, in this
      article, we first discuss the role of salivary cortisol in ambulatory monitoring.
      We start with a brief description of HPA axis regulation, and we then consider
      cortisol assessments in other organic materials, followed by a presentation of
      common salivary markers of HPA axis regulation suitable for ambulatory
      assessment. We further provide an overview on assessment designs and sources of
      variability within and between subjects (intervening variables), acknowledge the
      issue of (non)compliance, and address statistical aspects. We further give an
      overview of associations with psychosocial and health-related variables relevant
      for ambulatory assessment. Finally, we deal with preanalytical aspects of
      laboratory salivary cortisol analysis. The relative simplicity of salivary
      cortisol assessment protocols may lead to an overoptimistic view of the
      robustness of this method. We thus discuss several important issues related to
      the collection and storage of saliva samples and present empirical data on the
      stability of salivary cortisol measurements over time.

PMID- 22582341
TI  - Mapping structural influences on sex and HIV education in church and secular
      schools in Zimbabwe.
AB  - The authors used state-of-the-art concept mapping approaches to examine
      structural institutional effects of church and secular high schools on the types
      of sexual and HIV-prevention education messages transmitted to learners in
      Zimbabwe. Participants were school teachers (n = 26), school counselors (n = 28),
      and pastors involved in student pastoral care (n = 14; males = 27, females = 41).
      They reported on messages perceived to influence sexual decisions of learners in
      their school setting. The self-report data were clustered into message types
      using concept mapping and contrasted for consistency of content and structure
      both between and within type of school. The authors also engaged in curriculum
      document study with member checks in the participant schools to determine
      convergence of the evidence on school-type effects of the messages transmitted to
      students. Church schools prioritized faith-informed sexual and HIV-prevention
      messages, whereas both types of schools prioritized Life skills education and a
      future focus. Secular schools prioritized sex and HIV messages in the context of
      community norms. Facts about HIV and AIDS were relatively underemphasized by
      church schools. The implicit knowledge values that differentiate types of schools
      influence learner access to information important for their sexual decisions.

PMID- 22582340
TI  - Daily psychological demands are associated with 6-year progression of carotid
      artery atherosclerosis: the Pittsburgh Healthy Heart Project.
AB  - OBJECTIVE: We examine associations between the perception of ongoing
      psychological demands by ecological momentary assessment (EMA) and 6-year changes
      in carotid artery atherosclerosis by ultrasonography. METHODS: A total of 270
      initially healthy participants collected ambulatory blood pressure (ABP) and
      recorded their daily experiences, using electronic diaries, during two 3-day
      periods. Mean intima-media thickness (IMT) and plaque were assessed in the
      carotid arteries using B-mode ultrasound at baseline and again during a 6-year
      follow-up (mean follow-up duration = 73 months). RESULTS: Among those who had no
      exposure to antihypertensive medications during the course of follow-up (n =
      192), daily psychological demands were associated with greater progression of IMT
      as well as plaque, after adjusting for demographic and risk factor covariates.
      Associations between demands and plaque change were partially accounted for by
      ABP differences among those reporting high demands. Among those who were employed
      at baseline (n = 117), 6-year IMT changes were more strongly associated with
      ratings of daily demands than with traditional measures of occupational stress.
      CONCLUSIONS: These data support the role of psychological demands as a correlate
      of subclinical atherosclerotic progression, they point to ABP as a potential
      mechanism facilitating these effects, and they highlight the utility of EMA
      measures for capturing daily psychological demands with potential effects on
      health.

PMID- 22582342
TI  - Initial evaluation of a smoking cessation program incorporating physical activity
      promotion to Greek adults in antismoking clinics.
AB  - The purpose of this study was to evaluate an initial application of a smoking
      cessation program that integrated the promotion of physical activity (PA) as a
      cessation aid to Greek adults in antismoking clinics. From an initial pool of 50,
      12 men and 28 women from Central Greece completed the program, and 18 of them
      succeeded in quitting for 1 year after the program. Additionally, after the
      program, they increased their PA. Suggestions for future applications of the
      program are further discussed.

PMID- 22582343
TI  - Children's behavior problems in the United States and Great Britain.
AB  - We analyze the effects of family capital on child behavior problems in the United
      States and Great Britain by comparing a longitudinal survey sample of 5- to 13
      year-old children from the 1994 National Longitudinal Survey of Youth (N = 3,864)
      with a similar sample of children from the 1991 National Child Development Study
      "British Child" (N = 1,430). Findings suggest that in both societies, male
      children, those with health problems, and those whose mothers are divorced are at
      increased risk for behavior problems, while those with stronger home environments
      are at reduced risk. Family structure effects are more pervasive in Great Britain
      than in the United States, although some of these findings are a function of our
      racially diverse U.S. sample. We conclude that parents are important in both
      societies in promoting child social adjustment, and evidence that the more
      developed welfare state in Great Britain may substitute for capital at home is
      weak.

PMID- 22582344
TI  - Clinical-pathological characterization of diabetic foot infections: grading the
      severity of osteomyelitis.
AB  - The present study has 3 aims: (a) to characterize the clinical and pathological
      features of diabetic foot infections, (b) to show the range of clinical
      presentations of moderate infections, and (c) to analyze the different behavior
      of diabetic foot osteomyelitis regarding to its clinical presentation. A
      definitive diagnosis of the type of infection was made based on intraoperative
      findings and histopathology. Diabetic foot infections were classified into 2
      types: soft tissue and bone infections. Mild infections were always superficial.
      Severe infections included 75% of necrotizing soft tissue infections. Moderate
      infections showed ample range of clinical presentations. Eighty-one patients
      presented osteomyelitis. Osteomyelitis was further classified as follows:
      osteomyelitis without ischemia and without soft tissue involvement (class 1),
      osteomyelitis with ischemia without soft tissue involvement (class 2),
      osteomyelitis with soft tissue involvement (class 3), and osteomyelitis with
      ischemia and soft tissue involvement (class 4). Forty-eight patients (59.3%) with
      osteomyelitis underwent conservative surgery, 32 (39.5%) had minor amputations
      including 9 open transmetatarsal amputations, and there was 1 (1.2%) major
      amputation. The characterization of osteomyelitis into 4 classes showed a
      statistically significant trend toward increased severity and increased
      amputation rate and mortality. In conclusion, the clinical presentation of foot
      infections in diabetic patients is very heterogeneous and can be classified into
      soft tissue infections (cellulitis, superficial and deep abscesses, and
      necrotizing soft tissue infections) and osteomyelitis, which was the most
      frequent type of infection found in the author's series. Their division into 4
      classes showed a statistically significant trend toward increased severity,
      amputation rate, and mortality. The diagnosis of deep soft tissue infections
      associated with osteomyelitis may be difficult to achieve before surgery.

PMID- 22582345
TI  - Characterization of TLR4-mediated auto-antibody production in a mouse model of
      histidyl-tRNA synthetase-induced myositis.
AB  - We have previously shown that intramuscular immunization with a recombinant
      fragment of murine histidyl-tRNA synthetase (HRS) in the absence of exogenous
      adjuvant generates Ag-specific, IgG class switched Abs a murine model of
      myositis. Markedly diminished IgG anti-HRS auto-Ab responses in TLR4 signaling
      deficient C3H/HeJ mice indicate that TLR4 is required for auto-Ab formation
      and/or class switching in this system. Comparative time course assessment of HRS
      immunized C3H/HeOuJ (wild type) and C3H/HeJ (TLR4 mutant) mice shows here that
      despite significant impairment of class switched IgG anti-HRS responses in TLR4
      deficient C3H/HeJ mice, production of IgM anti-HRS auto-Abs is relatively
      preserved-suggesting that TLR4-mediated signals modulate IgG class switching
      rather than auto-Ab formation in this genetic background. In C57BL/6-derived
      knockout mice lacking either MyD88 (B6.MyD88(-/-)) or TRIF (B6.TRIF(-/-)) adaptor
      molecules, immunization studies indicate that TRIF exerts a dominant role in the
      generation of HRS-specific IgG auto-Abs. Complementing these analyses, in vitro
      stimulation of unfractionated, as well as T cell-depleted, C3H/HeOuJ splenocytes
      with recombinant murine HRS reveals that TLR4-mediated generation of class
      switched auto-Abs can occur independently of T cell help. Overall, these findings
      support a broader role for TLR4 in the breakdown of immune tolerance and
      development of autoimmunity.

PMID- 22582347
TI  - "Why is this so hard?" A review of detection of malingered ADHD in college
      students.
AB  - OBJECTIVE: The purpose of this article is to review studies that have
      investigated malingered ADHD in college students and offer recommendations for
      assessing effort in clinical evaluations of ADHD in college students. METHOD:
      This article identified and summarized nineteen peer-reviewed, empirical studies
      published between 2002 and 2011 that investigated malingered ADHD in college
      students. RESULTS: Few of the measures examined proved useful for detecting
      malingered ADHD. Most self-report questionnaires were not sensitive to
      malingering. While there is some variability in the usefulness of
      neuropsychological test failure, profiles between malingerers and individuals
      with ADHD are too similar to confidently detect malingered ADHD. Failure of three
      or more symptom validity tests proved most useful at detecting malingered ADHD.
      CONCLUSION: This review suggests that there is substantial need for measures
      designed specifically for detecting malingered ADHD. Simulators are able to
      produce plausible profiles on most tools used to diagnose ADHD.

PMID- 22582346
TI  - Suicide in the absence of mental disorder? A review of psychological autopsy
      studies across countries.
AB  - BACKGROUND: While numerous past reviews of psychological autopsy (PA) studies
      have examined the relationship between mental disorder and suicide, there has
      been little systematic investigation of suicide occurring in the absence of any
      identifiable psychiatric condition. AIM: This article reviews available
      literature on the topic by considering Axis I, sub-threshold, mild disorders and
      personality disorders. METHOD: We conducted a systematic review of PA studies
      from 2000 onwards. Studies included in the review had to clearly describe the
      proportion of suicide cases without a classifiable mental disorder or sub
      threshold condition. RESULTS: Up to 66.7% of suicide cases remained without
      diagnosis in those studies that only examined Axis I disorders (n = 14).
      Approximately 37.1% of suicide cases had no psychiatric condition in research
      papers that assessed personality and Axis I disorders (n = 9), and 37% of
      suicides had no Axis I, sub-threshold/mild conditions (n = 6). In general, areas
      in China and India had a higher proportion of suicides without a diagnosis than
      studies based in Europe, North America or Canada. CONCLUSION: Variation in the
      proportion of suicide cases without a psychiatric condition may reflect cultural
      specificities in the conceptualization and diagnosis of mental disorder, as well
      as methodological and design-related differences between studies.

PMID- 22582348
TI  - Severity of symptoms and quality of life in medical students with ADHD.
AB  - OBJECTIVE: In this study, the authors examined the severity of ADHD symptoms and
      related quality of life in 1st and 2nd year medical students diagnosed with ADHD.
      METHOD: The sample consists of 33 preclinical medical students previously
      diagnosed with ADHD. The Adult ADHD Quality of Life Scale (AAQoL) and Adult ADHD
      Self-Reported Checklist were administered. RESULTS: Participants' ADHD-related
      quality of life and life productivity were negatively correlated with the
      severity of their ADHD symptoms. Students receiving academic accommodations
      reported significantly higher ADHD symptoms. The presence of a comorbid condition
      contributed to significantly lower psychological health scores. Unexpectedly,
      women had significantly lower quality of life (AAQoL total score) and
      significantly lower psychological health scores than men. CONCLUSION: Since the
      majority of the sample reported severe ADHD symptoms while receiving medication
      treatment, the authors have concluded that it is important to develop
      psychosocial treatments to manage the associated distress from residual symptoms
      in medical students with ADHD.

PMID- 22582350
TI  - Blunt polytrauma: evaluation with 64-section whole-body CT angiography.
AB  - Blunt polytrauma remains a leading cause of death and disability worldwide. With
      the major advances in computed tomography (CT) technology over the past decade,
      whole-body CT is increasingly recognized as the emerging standard for providing
      rapid and accurate diagnoses within the narrow therapeutic window afforded to
      trauma victims with multiple severe injuries. With a single continuous
      acquisition, whole-body CT angiography is able to demonstrate all potentially
      injured organs, as well as vascular and bone structures, from the circle of
      Willis to the symphysis pubis. As its use becomes more widespread, the large
      volume of information inherent to whole-body CT poses new challenges to
      radiologists in providing efficient and timely interpretation. An awareness of
      trauma scoring systems and injury mechanisms is essential to maintain an
      appropriate level of suspicion in the search for multiple injuries, and the use
      of multiplanar reformation and three-dimensional postprocessing techniques is
      important to maximize efficiency in the search. Knowledge of the key injuries
      that require urgent surgical or percutaneous intervention, including major
      vascular injuries and active hemorrhage, diaphragmatic rupture, unstable spinal
      fractures, pancreatic injuries with ductal involvement, and injuries to the
      mesentery and hollow viscera, is also necessary.

PMID- 22582349
TI  - Duloxetine in adults with ADHD: a randomized, placebo-controlled pilot study.
AB  - OBJECTIVE: To assess the effect of duloxetine on ADHD in adults. METHOD: In a 6
      week double-blind trial, 30 adults with ADHD received placebo or duloxetine 60 mg
      daily. The Conners' Adult ADHD Rating Scale (CAARS) and the Clinical Global
      Impression Scales (CGI) were used to assess symptom severity and clinical
      improvement. The Hamilton Anxiety Rating Scale (HARS) and the Hamilton Depression
      Rating Scale (HDRS) were used to measure the effect on anxiety and depressive
      symptoms. RESULTS: The Duloxetine group showed lower score on CGI-Severity at
      Week 6 (3.00 vs. 4.07 for placebo, p < .001), greater improvement on CGI
      Improvement (2.89 vs. 4.00 at Week 6, p < .001), and greater decreases on five of
      eight subscales of the CAARS. There was no treatment group effect on HDRS or HARS
      scores. CONCLUSION: Duloxetine may be a therapeutic option for adults with ADHD,
      but further studies are required to replicate these findings in larger samples.

PMID- 22582351
TI  - Imaging patients with cardiac trauma.
AB  - In the United States, trauma is the leading cause of death among those who are 1
      44 years old, with cardiovascular injuries representing the second most common
      cause of traumatic death after central nervous system injuries. Evaluation of
      trauma patients with suspected cardiac injury may be complex and include
      electrocardiography, measurement of cardiac biomarkers, and imaging examinations.
      Contrast material-enhanced computed tomography (CT) has become one of the most
      valuable imaging tools available for evaluating hemodynamically stable patients
      with suspected cardiac injury. The presence of hemopericardium, with or without
      cardiac tamponade, is one of the most significant findings of cardiac injury.
      Other complications that result from blunt cardiac injury, such as pericardial
      rupture and cardiac herniation, may be readily depicted at multidetector CT.
      Assessment of patients with cardiac injuries, particularly those with penetrating
      injuries, is a challenging and time-critical matter, with clinical and imaging
      findings having complementary roles in the formation of an accurate diagnosis.
      Patients who are hemodynamically stable, particularly those with penetrating
      cardiac injuries, also may benefit from a timely imaging examination. In addition
      to chest radiography, other available modalities such as transthoracic and
      transesophageal echocardiography, nuclear medicine, and magnetic resonance
      imaging may play a role in selected cases.

PMID- 22582352
TI  - Emergent pediatric US: what every radiologist should know.
AB  - Appendicitis, intussusception, and hypertrophic pyloric stenosis (HPS) are three
      of the most common reasons for emergent abdominal imaging in pediatric patients.
      Although the use of computed tomography has risen dramatically over the past 2
      decades, children are particularly at risk for the adverse effects of ionizing
      radiation, and even low-dose radiation is associated with a small but significant
      increase in lifetime risk of fatal cancer. In most emergency departments, the use
      of magnetic resonance (MR) imaging as a primary modality for the evaluation of a
      child with abdominal pain remains impractical due to its high cost, its limited
      availability, and the frequent need for sedation. Ultrasonography (US) does not
      involve ionizing radiation and, unlike MR imaging, is relatively inexpensive, is
      widely available, and does not require sedation. Another major advantage of US in
      abdominal imaging is that it allows dynamic assessment of bowel peristalsis and
      compressibility. Delayed diagnosis of any of the aforementioned disease processes
      can lead to serious morbidity and, in some cases, death. The ability to diagnose
      or exclude disease with US should be part of a core radiology skill set for any
      practice that includes a pediatric population.

PMID- 22582353
TI  - Clinical and imaging features of intracranial arterial aneurysms in the pediatric
      population.
AB  - Intracranial arterial aneurysms (IAAs) are rare in children. Nevertheless, IAAs
      account for at least 10%-15% of hemorrhagic strokes during the first 2 decades of
      life. Traditional vascular risk factors, which are common in the adult
      population, are generally absent in the pediatric population, engendering
      distinct modes of IAA pathogenesis. Classification of pediatric IAAs according to
      the pathogenetic mechanism shows eight distinct categories: idiopathic,
      traumatic, those due to excessive hemodynamic stress, vasculopathic, infectious,
      noninfectious inflammatory, oncotic, and familial. Pathogenetic mechanism is the
      best predictor of the clinical course of the disease, response to treatment, and
      long-term prognosis. The pathogenetic subtypes of pediatric IAA show
      characteristic and variably overlapping features. In most cases, IAAs manifesting
      during the first 2 decades of life are idiopathic. IAAs that are idiopathic,
      traumatic (second most common type), or due to excessive hemodynamic stresses
      (third most common type) account for more than 80% of IAAs in the pediatric age
      group. Most of the remaining pediatric IAAs are the result of congenital cerebral
      aneurysmal arteriopathies or infection. Multiple IAAs are unusual in young
      children except in those with acquired (secondary to immune deficiency states) or
      congenital cerebral aneurysmal arteriopathies or infectious IAAs.

PMID- 22582354
TI  - CT and MR imaging of the inner ear and brain in children with congenital
      sensorineural hearing loss.
AB  - Imaging plays an important role in the evaluation of congenital sensorineural
      hearing loss. In children who are candidates for cochlear implantation surgery,
      it provides vital preoperative information about the inner ear, the
      vestibulocochlear nerve, and the brain. High-resolution computed tomography (CT)
      and magnetic resonance (MR) imaging provide excellent delineation of the
      intricate anatomy of the inner ear: CT depicts the minute details of osseous
      structures, and MR imaging allows visualization of the fluid-filled spaces and
      the vestibulocochlear nerve. Together, these complementary modalities can aid
      decision making about the best management strategy by facilitating the
      identification and characterization of inner ear malformations and any associated
      neurologic abnormalities. It is important that the radiologist be familiar with
      the key imaging features when interpreting CT and MR images obtained in this
      patient group. A broad spectrum of inner ear malformations have been described
      and linked to developmental insults at different stages of embryogenesis, and
      various systems have been proposed for classifying them. In this article, these
      malformations are described by using classification systems used by
      otolaryngologists for ease of interpretation. The relevant normal anatomy and
      development of the inner ear are briefly surveyed, standard imaging protocols for
      studying the inner ear are reviewed, and the imaging appearances of frequently
      observed inner ear malformations are described and illustrated. The impact of the
      identification of these malformations and commonly associated brain abnormalities
      on clinical management and prognosis also is discussed.

PMID- 22582355
TI  - Your brain on drugs: imaging of drug-related changes in the central nervous
      system.
AB  - Drug abuse is a substantial problem in society today and is associated with
      significant morbidity and mortality. Various drugs are associated with serious
      complications affecting the brain, and it is critical to recognize the imaging
      findings of these complications to provide prompt medical management. The central
      nervous system (CNS) is a target organ for drugs of abuse as well as specific
      prescribed medications. Drugs of abuse affecting the CNS include cocaine, heroin,
      alcohol, amphetamines, toluene, and cannabis. Prescribed medications or medical
      therapies that can affect the CNS include immunosuppressants, antiepileptics,
      nitrous oxide, and total parenteral nutrition. The CNS complications of these
      drugs include neurovascular complications, encephalopathy, atrophy, infection,
      changes in the corpus callosum, and other miscellaneous changes. Imaging
      abnormalities indicative of these complications can be appreciated at both
      magnetic resonance (MR) imaging and computed tomography (CT). It is critical for
      radiologists to recognize complications related to drugs of abuse as well as
      iatrogenic effects of various medications. Therefore, diagnostic imaging
      modalities such as MR imaging and CT can play a pivotal role in the recognition
      and timely management of drug-related complications in the CNS.

PMID- 22582356
TI  - Unilateral vocal cord paralysis: a review of CT findings, mediastinal causes, and
      the course of the recurrent laryngeal nerves.
AB  - Vocal cord paralysis (VCP) may be caused by a variety of mediastinal disease
      entities, including various neoplastic, inflammatory, and vascular conditions,
      and may be the presenting symptom of an otherwise clinically occult disease.
      Familiarity with the spectrum of thoracic diseases that can result in VCP and
      inclusion of the mediastinum to the level of the aorticopulmonary window (left
      side) or brachiocephalic artery (right side) in computed tomographic (CT) studies
      performed for VCP are essential. VCP can be reliably identified at CT by
      recognizing key findings at the level of the true vocal cords and aryepiglottic
      folds. Although there are a number of VCP mimics and imaging pitfalls, they can
      generally be avoided by carefully assessing the scan plane and level and
      evaluating for additional findings. By understanding and assessing the entire
      course of the vagus and recurrent laryngeal nerves, the radiologist can avoid
      missing causative lesions, many of which have a clinical significance far beyond
      that of the VCP itself.

PMID- 22582357
TI  - Multidetector CT evaluation of the postoperative pancreas.
AB  - Several pancreatic diseases may require surgical treatment, with most of these
      procedures classified as resection or drainage. Resection procedures, which are
      usually performed to remove pancreatic tumors, include pancreatoduodenectomy,
      central pancreatectomy, distal pancreatectomy, and total pancreatectomy. Drainage
      procedures are usually performed to treat chronic pancreatitis after the failure
      of medical therapy and include the Puestow and Frey procedures. The type of
      surgery depends not only on the patient's symptoms and the location of the
      disease, but also on the expertise of the surgeon. Radiologists should become
      familiar with these surgical procedures to better understand postoperative
      changes in anatomic findings. Multidetector computed tomography is the modality
      of choice for identifying normal findings after surgery, postoperative
      complications, and tumor recurrence in patients who have undergone pancreatic
      surgery.

PMID- 22582358
TI  - MR imaging of hypervascular lesions in the cirrhotic liver: a diagnostic dilemma.
AB  - Cirrhosis is characterized by a spectrum of hepatocellular nodules that mark the
      progression from regenerative nodules to low- and high-grade dysplastic nodules,
      followed by small and large hepatocellular carcinomas (HCCs). Characterization of
      small nodules on the basis of imaging and histopathologic findings is complicated
      by an overlap in findings associated with each type of nodule, a reflection of
      their multistep transitions. Vascularity patterns change gradually as the nodules
      evolve, with an increasing shift from predominantly venous to predominantly
      arterial perfusion. Regenerative and low-grade dysplastic nodules demonstrate
      predominantly portal perfusion and contrast enhancement similar to that of
      surrounding parenchyma. Differentiation of high-grade dysplastic nodules and well
      differentiated HCCs on the basis of dynamic imaging and histologic findings is
      challenging, with a high rate of false-negative results. Some small nodules that
      lack hypervascularity may be early HCCs. Progressed small and large HCCs usually
      present no diagnostic difficulty because of their characteristic findings.
      Although characterization of hypervascular lesions in the cirrhotic liver is
      difficult, it is a key step in disease management and is the radiologist's
      responsibility.

PMID- 22582359
TI  - AIRP best cases in radiologic-pathologic correlation: Hepatic epithelioid
      hemangioendothelioma.

PMID- 22582360
TI  - Uncommon primary pelvic retroperitoneal masses in adults: a pattern-based imaging
      approach.
AB  - There is a broad spectrum of primary pelvic retroperitoneal masses in adults that
      demonstrate characteristic epidemiologic and histopathologic features and natural
      histories. These masses may be classified into five distinct subgroups using a
      pattern-based approach that takes anatomic distribution and certain imaging
      characteristics into account, allowing greater accuracy in their detection and
      characterization and helping to optimize patient management. The five groups are
      cystic (serous and mucinous epithelial neoplasms, pelvic lymphangioma, tailgut
      cyst, ancient schwannoma), vascular or hypervascular (solitary fibrous tumor,
      paraganglioma, pelvic arteriovenous malformation, Klippel-Trenaunay-Weber
      syndrome, extraintestinal GIST [gastrointestinal stromal tumor]), fat-containing
      (lipoma, liposarcoma, myelolipoma, presacral teratoma), calcified (calcified
      lymphocele, calcified rejected transplant kidney, rare sarcomas), and myxoid
      (schwannoma, plexiform neurofibroma, myxoma).Cross-sectional imaging modalities
      help differentiate the more common gynecologic neoplasms from more unusual
      masses. In particular, the tissue-specific multiplanar capability of high
      resolution magnetic resonance imaging permits better tumor localization and
      internal characterization, thereby serving as a road map for surgery.

PMID- 22582361
TI  - Imaging-guided prostate biopsy: conventional and emerging techniques.
AB  - Transrectal ultrasonography (US)-guided biopsy is the standard approach for
      histopathologic diagnosis of prostate cancer. However, this technique has
      multiple limitations owing to the operator's inability in most cases to directly
      visualize and target prostate lesions. Magnetic resonance (MR) imaging of the
      prostate overcomes many of these limitations by directly depicting areas of
      abnormality and allowing targeted biopsies. Accuracy in the detection of prostate
      cancer is improved by the combined use of standard T2-weighted MR imaging and
      advanced MR imaging techniques such as diffusion-weighted imaging, dynamic
      contrast-enhanced imaging, and MR spectroscopy. Suspicious-appearing regions of
      the prostate seen on MR images can be targeted at real-time transrectal US-guided
      biopsy to improve the diagnostic yield. MR imaging also can be performed for real
      time guidance of transrectal prostate biopsy. Studies among patients who
      underwent at least one transrectal US-guided biopsy with a negative result before
      undergoing an MR imaging-guided biopsy showed improved detection rates with MR
      imaging-guided biopsy in comparison with the detection rates achieved with a
      repeat transrectal US-guided biopsy; however, MR imaging-guided biopsy is a more
      time-consuming procedure. A technique known as fused MR imaging- and transrectal
      US-guided biopsy, which relies on the coregistration of previously acquired MR
      images with real-time transrectal US images acquired during the procedure, shows
      promise but is limited by deformation of the prostate; this limitation is the
      subject of ongoing investigation. Another technique that is currently under
      investigation, MR imaging-guided prostate biopsy with robotic assistance, may one
      day help improve the accuracy of biopsy needle placement.

PMID- 22582362
TI  - AIRP best cases in radiologic-pathologic correlation: Genitourinary tuberculosis.

PMID- 22582363
TI  - MR imaging of malignancies arising in endometriomas and extraovarian
      endometriosis.
AB  - Cancers that arise in ovarian or extraovarian endometriosis are a distinct
      disease category with a histologic profile different from that of the more common
      epithelial ovarian cancers and with a better prognosis. Because the malignant
      transformation of endometriomas is rarely associated with lymphadenopathy or
      peritoneal carcinomatosis, a high index of suspicion on the part of the
      radiologist is necessary to establish a timely diagnosis of endometriosis-related
      ovarian cancers and allow appropriate oncologic management. Although imaging is
      not currently performed for surveillance of endometriosis, magnetic resonance
      (MR) imaging is often performed when surgical treatment is under consideration.
      An optimal MR imaging protocol for the detection of cancer arising in an
      endometrioma includes a review of subtraction images derived from unenhanced and
      contrast material-enhanced T1-weighted datasets. Subtraction images provide
      improved conspicuity of enhancing mural nodules--which are the most sensitive MR
      imaging sign of malignancy in ovarian endometriosis--against the background of
      the high-signal-intensity endometriotic cyst. Cancers arising in extraovarian
      endometriosis typically manifest as solid lesions with intermediate signal
      intensity on T1- and T2-weighted images, enhancement after the intravenous
      administration of a gadolinium-based contrast material, and restricted diffusion
      on diffusion-weighted images and apparent diffusion coefficient (ADC) maps. The
      signal intensity of myometrium, or, if the uterus is absent, that of the small
      bowel wall, is used as an internal reference standard for lesion signal
      intensity. Lesions are considered to have restricted diffusion if they show
      signal hyperintensity relative to the reference structure on diffusion-weighted
      images and hypointensity or isointensity relative to that structure on ADC maps.
      For definitive diagnosis, histopathologic analysis is required.

PMID- 22582364
TI  - Pediatric osteomyelitis: a scintigraphic case-based review.
AB  - This review presents techniques to optimize bone scintigraphy for evaluation of
      the spectrum of abnormalities associated with pediatric osteomyelitis, with an
      emphasis on the approaches to patient preparation and positioning and to
      interpretation. The diagnosis of pediatric osteomyelitis can be challenging for
      several different reasons. Bone scintigraphy is especially useful when the site
      of osteomyelitis is unclear. Other imaging modalities, including radiography,
      ultrasonography, and magnetic resonance imaging, all have advantages and may have
      a role in evaluating the condition of the child with osteomyelitis.
      Pathophysiologic considerations unique to children contribute to a different
      clinical presentation of osteomyelitis in the pediatric population than that seen
      in adults. In addition, patient movement degrades image quality substantially,
      which is an important consideration for imaging children. Neonates have a higher
      incidence of multifocal osteomyelitis, and they represent a unique subset of the
      pediatric population with separate considerations. Several examples illustrate
      techniques to optimize imaging, as well as show the spectrum of abnormalities
      associated with pediatric osteomyelitis. Careful attention to bone scintigraphic
      technique ensures that high-quality images can be obtained, which will allow
      confident diagnosis of pediatric osteomyelitis.

PMID- 22582365
TI  - Current perspectives on the advantages of 3-T MR imaging of the wrist.
AB  - The use of 3-T magnetic resonance (MR) imaging systems with improved coil designs
      and high-resolution MR imaging sequences allows visualization of the
      musculoskeletal anatomy in exquisite detail and accurate characterization of
      abnormalities both in soft tissues and in bone. Current high-field-strength MR
      systems offer particular advantages for diagnostic imaging of the small joints of
      the extremities, especially the wrists, where multiple overlapping soft-tissue
      structures may be visually inseparable at lower field strengths because of
      limited contrast resolution. Diagnostic accuracy obtained with 3-T MR imaging of
      the wrist performed with an acquisition protocol that includes three-dimensional
      and proton density-weighted imaging sequences is nearly commensurate with that
      obtained with MR arthrography. Abnormalities of the ligaments, tendons,
      cartilage, nerves, blood vessels, and bone are clearly depicted, allowing
      accurate characterization of perforations, tears, and fractures, as well as
      various soft-tissue and intraosseous lesions (eg, ganglion cysts), vascular
      malformations, aneurysms, and neuropathies.

PMID- 22582366
TI  - Challenges encountered and lessons learned in initial experience with the next
      generation of interactive radiology literature in RadioGraphics.

PMID- 22582367
TI  - Re: Inverted "V": a unique variation in the branching pattern of the portal
      venous system.

PMID- 22582368
TI  - Evaluation with cardiovascular MR imaging of baffles and conduits used in
      palliation or repair of congenital heart disease.
AB  - A wide array of baffles and conduits are used in repair or palliation of
      congenital heart disease, which is the most common major birth defect, often with
      complex redirection of blood flow to achieve a more stable physiology.
      Cardiovascular magnetic resonance (CMR) imaging is an increasingly used modality
      for noninvasive assessment of anatomy and physiology both before and after
      surgical intervention, with highly reproducible measurements of ventricular size
      and function, quantification of valvular insufficiency and flow volumes, and
      excellent delineation of intracardiac and extracardiac anatomy. The authors
      review the indications, appearances on CMR images, and potential complications of
      various cardiovascular baffles and conduits: Mustard and Senning procedures,
      venoatrial baffles, intraventricular baffles, ventriculoarterial conduits, and
      baffles and conduits used in functional single-ventricle palliation. CMR imaging
      offers the most complete evaluation of single-ventricle anatomy and physiology,
      demonstrating the anatomy of venous pathways and pulmonary arteries and
      quantifying systemic ventricular size and systolic function, differential
      pulmonary blood flow, ratio of pulmonary to systemic blood flow, and
      aortopulmonary collateral flow. Anatomic and physiologic considerations are
      discussed, and suggested CMR imaging protocols and practical advice for
      performing and interpreting CMR studies are provided. The diversity and
      complexity of baffles and conduits complicates performance and interpretation of
      studies in this population, but a fundamental understanding of the goals of the
      procedure, postoperative physiology, and potential complications allows targeted
      imaging and precise reporting of clinically significant findings. Supplemental
      material available at
      http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.323115096/-/DC1.

PMID- 22582369
TI  - Interactive Web-based learning module on CT of the temporal bone: anatomy and
      pathology.
AB  - An interactive Web-based learning module on the temporal bone has been developed.
      It shows normal temporal bone anatomy in four imaging planes: axial, coronal, and
      parallel and perpendicular to the long axis of the petrous bone. After reviewing
      the normal anatomy, users should be able to identify key imaging features of
      pathologic conditions of the temporal bone. Children with congenital
      abnormalities of the temporal bone may present with conductive or sensorineural
      hearing loss or both and may have a genetic syndrome. Acute otitis media is the
      most common infection of the temporal bone and is most prevalent among children.
      Although imaging is unnecessary in uncomplicated otitis media, it is important
      for evaluation of infectious complications. Classically, temporal bone fractures
      were described as longitudinal or transverse with respect to the long axis of the
      petrous bone. However, it is increasingly recognized that many fractures have
      both longitudinal and transverse components. Patients with temporal bone
      fractures may have conductive or sensorineural hearing loss in addition to other
      complications. The most common tumor of the temporal bone at the cerebellopontine
      angle is the vestibular schwannoma. Paraganglioma is the second most common tumor
      of the temporal bone and the most common tumor of the middle ear. Supplemental
      material available at http://uwmsk.org/temporalbone/atlas.html.

PMID- 22582370
TI  - Genome sequence of Lactobacillus salivarius SMXD51, a potential probiotic strain
      isolated from chicken cecum, showing anti-campylobacter activity.
AB  - We report the draft genome sequence of Lactobacillus salivarius SMXD51, isolated
      from the cecum of healthy chickens showing an activity against Campylobacter--the
      food-borne pathogen that is the most common cause of gastroenteritis in the
      European Union (EU)--and potentially interesting features for a probiotic strain,
      explaining our interest in it.

PMID- 22582371
TI  - Draft genome sequence of a Sphingomonas sp., an endosymbiotic bacterium isolated
      from an arctic lichen Umbilicaria sp.
AB  - Sphingomonas sp. strain PAMC 26617 has been isolated from an Arctic lichen
      Umbilicaria sp. on the Svalbard Islands. Here we present the draft genome
      sequence of this strain, which represents a valuable resource for understanding
      the symbiotic mechanisms between endosymbiotic bacteria and lichens surviving in
      extreme environments.

PMID- 22582372
TI  - Complete genome sequence of the fruiting myxobacterium Corallococcus coralloides
      DSM 2259.
AB  - Corallococcus coralloides, like most other myxobacteria, undergoes a
      developmental program culminating in the formation of fruiting bodies. C.
      coralloides fruiting bodies are morphologically distinct from those of other
      fruiting myxobacteria for which full-length genome sequences are available. The
      genome sequence of the 10.0-Mb C. coralloides genome is presented herein.

PMID- 22582373
TI  - Complete genome sequence of Melissococcus plutonius DAT561, a strain that shows
      an unusual growth profile and is representative of an endemic cluster in Japan.
AB  - We report the complete genome sequence of Melissococcus plutonius DAT561, which
      is a causative agent of European foulbrood. M. plutonius DAT561 is a
      representative of nonfastidious strains isolated in Japan. The addition of
      potassium phosphate was not required for normal growth, unlike for typical M.
      plutonius strain/isolates.

PMID- 22582374
TI  - Genome sequence of the probiotic bacterium Sporolactobacillus vineae SL153T.
AB  - The novel Sporolactobacillus vineae SL153(T) strain has excellent intestinal
      adherence and growth inhibitory effect on pathogenic microorganisms, including
      Vibrio genus microorganisms, and therefore can be effectively used for the
      prevention and treatment of disease caused by pathogenic microorganisms. Here, we
      first report the draft genome sequence of a novel species in the genus
      Sporolactobacillus.

PMID- 22582375
TI  - Genome sequence of Kingella kingae septic arthritis isolate PYKK081.
AB  - Kingella kingae is a human oral bacterium that can cause infections of the
      skeletal system in children. The bacterium is also a cardiovascular pathogen
      causing infective endocarditis in children and adults. We report herein the draft
      genome sequence of septic arthritis K. kingae strain PYKK081.

PMID- 22582376
TI  - Genome sequences of the ethanol-tolerant Lactobacillus vini strains LMG 23202T
      and JP7.8.9.
AB  - We report on the genome sequences of Lactobacillus vini type strain LMG 23202(T)
      (DSM 20605) (isolated from fermenting grape musts in Spain) and the industrial
      strain L. vini JP7.8.9 (isolated from a bioethanol plant in northeast Brazil).
      All contigs were assembled using gsAssembler, and genes were predicted and
      annotated using Rapid Annotation using Subsystem Technology (RAST). The
      identified genome sequence of LMG 23202(T) had 2.201.333 bp, 37.6% G+C, and 1,833
      genes, whereas the identified genome sequence of JP7.8.9 had 2.301.037 bp, 37.8%
      G+C, and 1,739 genes. The gene repertoire of the species L. vini offers promising
      opportunities for biotechnological applications.

PMID- 22582377
TI  - Genome sequence of Pantoea sp. strain Sc 1, an opportunistic cotton pathogen.
AB  - Pantoea is comprised of a broad spectrum of species, including plant pathogens.
      Here, we provide an annotated genome sequence of Pantoea sp. strain Sc 1, which
      was isolated from a diseased cotton boll. This research provides the first genome
      sequence of a bona fide Pantoea sp. insect-vectored cotton pathogen.

PMID- 22582378
TI  - Complete genome sequence of Rahnella aquatilis CIP 78.65.
AB  - Rahnella aquatilis CIP 78.65 is a gammaproteobacterium isolated from a drinking
      water source in Lille, France. Here we report the complete genome sequence of
      Rahnella aquatilis CIP 78.65, the type strain of R. aquatilis.

PMID- 22582379
TI  - Genome sequence of Shigella flexneri serotype 5a strain M90T Sm.
AB  - Bacteria of the genus Shigella are a major cause of death worldwide (L. von
      Seidlein et al., PLoS Med. 3:e353, 2006). We sequenced the genome of Shigella
      flexneri strain M90T Sm (serotype 5a) and compared it to the published genome
      sequence of S. flexneri strain 8401 (serotype 5b).

PMID- 22582380
TI  - Draft genome of a Brazilian avian-pathogenic Escherichia coli strain and in
      silico characterization of virulence-related genes.
AB  - Avian-pathogenic Escherichia coli (APEC) strains cause extraintestinal diseases
      in avian species. Here, we present the draft genome of an APEC strain (SCI-07)
      from Brazil that was isolated from skin lesions (gelatinous edema) on the head
      and periorbital tissues of a laying hen with swollen head syndrome.

PMID- 22582381
TI  - Complete genome sequence of Flavobacterium indicum GPSTA100-9T, isolated from
      warm spring water.
AB  - We report here the complete annotated genome sequence of Flavobacterium indicum
      CIP 109464(T) (= GPTSA100-9(T)), isolated from warm spring water in Assam, India.
      The genome sequence of F. indicum revealed a number of interesting features and
      genes in relation to its environmental lifestyle.

PMID- 22582382
TI  - Draft genome sequences of the diarrheagenic Escherichia coli collection.
AB  - We report the draft genome sequences of the collection referred to as the
      Escherichia coli DECA collection, which was assembled to contain representative
      isolates of the 15 most common diarrheagenic clones in humans
      (http://shigatox.net/new/). These genomes represent a valuable resource to the
      community of researchers who examine these enteric pathogens.

PMID- 22582383
TI  - Genome sequence of Klebsiella oxytoca 11492-1, a nosocomial isolate possessing a
      FOX-5 AmpC beta-lactamase.
AB  - Klebsiella oxytoca strain 11492-1 was isolated from a perianal swab culture from
      a patient at the University of Maryland Medical Center in 2005. The K. oxytoca
      11492-1 draft genome contains multiple antibiotic resistance genes, including a
      FOX-5 AmpC beta-lactamase encoded on a large IncA/C plasmid.

PMID- 22582384
TI  - Genome sequence of Sphingomonas sp. strain PAMC 26621, an Arctic-lichen
      associated bacterium isolated from a Cetraria sp.
AB  - The lichen-associated bacterial strain Sphingomonas sp. PAMC 26621 was isolated
      from an Arctic lichen Cetraria sp. on Svalbard Islands. Here we report the draft
      genome sequence of this strain, which could provide novel insights into the
      molecular principles of lichen-microbe interactions.

PMID- 22582386
TI  - Retraction. Crystal structure of butyrate kinase 2 from Thermotoga maritima, a
      member of the ASKHA superfamily of phosphotransferases.

PMID- 22582385
TI  - Genome sequence of Xanthomonas citri pv. mangiferaeindicae strain LMG 941.
AB  - We report the 5.1-Mb genome sequence of Xanthomonas citri pv. mangiferaeindicae
      strain LMG 941, the causal agent of bacterial black spot in mango. Apart from
      evolutionary studies, the draft genome will be a valuable resource for the
      epidemiological studies and quarantine of this phytopathogen.

PMID- 22582387
TI  - All human granzymes target hnRNP K that is essential for tumor cell viability.
AB  - Granule exocytosis by cytotoxic lymphocytes is the key mechanism to eliminate
      virus-infected cells and tumor cells. These lytic granules contain the pore
      forming protein perforin and a set of five serine proteases called granzymes. All
      human granzymes display distinct substrate specificities and induce cell death by
      cleaving critical intracellular death substrates. In the present study, we show
      that all human granzymes directly cleaved the DNA/RNA-binding protein
      heterogeneous nuclear ribonucleoprotein K (hnRNP K), designating hnRNP K as the
      first known pan-granzyme substrate. Cleavage of hnRNP K was more efficient in the
      presence of RNA and occurred in two apparent proteolysis-sensitive amino acid
      regions, thereby dissecting the functional DNA/RNA-binding hnRNP K domains. HnRNP
      K was cleaved under physiological conditions when purified granzymes were
      delivered into living tumor cells and during lymphokine-activated killer cell
      mediated attack. HnRNP K is essential for tumor cell viability, since knockdown
      of hnRNP K resulted in spontaneous tumor cell apoptosis with caspase activation
      and reactive oxygen species production. This apoptosis was more pronounced at low
      tumor cell density where hnRNP K knockdown also triggered a caspase-independent
      apoptotic pathway. This suggests that hnRNP K promotes tumor cell survival in the
      absence of cell-cell contact. Silencing of hnRNP K protein expression rendered
      tumor cells more susceptible to cellular cytotoxicity. We conclude that hnRNP K
      is indispensable for tumor cell viability and our data suggest that targeting of
      hnRNP K by granzymes contributes to or reinforces the cell death mechanisms by
      which cytotoxic lymphocytes eliminate tumor cells.

PMID- 22582388
TI  - Linear chromosome-generating system of Agrobacterium tumefaciens C58:
      protelomerase generates and protects hairpin ends.
AB  - Agrobacterium tumefaciens C58, the pathogenic bacteria that causes crown gall
      disease in plants, harbors one circular and one linear chromosome and two
      circular plasmids. The telomeres of its unusual linear chromosome are covalently
      closed hairpins. The circular and linear chromosomes co-segregate and are stably
      maintained in the organism. We have determined the sequence of the two ends of
      the linear chromosome thus completing the previously published genome sequence of
      A. tumefaciens C58. We found that the telomeres carry nearly identical 25-bp
      sequences at the hairpin ends that are related by dyad symmetry. We further
      showed that its Atu2523 gene encodes a protelomerase (resolvase) and that the
      purified enzyme can generate the linear chromosomal closed hairpin ends in a
      sequence-specific manner. Agrobacterium protelomerase, whose presence is
      apparently limited to biovar 1 strains, acts via a cleavage-and-religation
      mechanism by making a pair of transient staggered nicks invariably at 6-bp
      spacing as the reaction intermediate. The enzyme can be significantly shortened
      at both the N and C termini and still maintain its enzymatic activity. Although
      the full-length enzyme can uniquely bind to its product telomeres, the N-terminal
      truncations cannot. The target site can also be shortened from the native 50-bp
      inverted repeat to 26 bp; thus, the Agrobacterium hairpin-generating system
      represents the most compact activity of all hairpin linear chromosome- and
      plasmid-generating systems to date. The biochemical analyses of the protelomerase
      reactions further revealed that the tip of the hairpin telomere may be unusually
      polymorphically capable of accommodating any nucleotide.

PMID- 22582389
TI  - Reconstitution of vacuolar-type rotary H+-ATPase/synthase from Thermus
      thermophilus.
AB  - Vacuolar-type rotary H(+)-ATPase/synthase (V(o)V(1)) from Thermus thermophilus,
      composed of nine subunits, A, B, D, F, C, E, G, I, and L, has been reconstituted
      from individually isolated V(1) (A(3)B(3)D(1)F(1)) and V(o)
      (C(1)E(2)G(2)I(1)L(12)) subcomplexes in vitro. A(3)B(3)D and A(3)B(3) also
      reconstituted with V(o), resulting in a holoenzyme-like complexes. However,
      A(3)B(3)D-V(o) and A(3)B(3)-V(o) did not show ATP synthesis and
      dicyclohexylcarbodiimide-sensitive ATPase activity. The reconstitution process
      was monitored in real time by fluorescence resonance energy transfer (FRET)
      between an acceptor dye attached to subunit F or D in V(1) or A(3)B(3)D and a
      donor dye attached to subunit C in V(o). The estimated dissociation constants
      K(d) for V(o)V(1) and A(3)B(3)D-V(o) were ~0.3 and ~1 nm at 25  degrees C,
      respectively. These results suggest that the A(3)B(3) domain tightly associated
      with the two EG peripheral stalks of V(o), even in the absence of the central
      shaft subunits. In addition, F subunit is essential for coupling of ATP
      hydrolysis and proton translocation and has a key role in the stability of whole
      complex. However, the contribution of the F subunit to the association of
      A(3)B(3) with V(o) is much lower than that of the EG peripheral stalks.

PMID- 22582390
TI  - Homeostatic synaptic scaling is regulated by protein SUMOylation.
AB  - Homeostatic scaling allows neurons to alter synaptic transmission to compensate
      for changes in network activity. Here, we show that suppression of network
      activity with tetrodotoxin, which increases surface expression of AMPA receptors
      (AMPARs), dramatically reduces levels of the deSUMOylating (where SUMO is small
      ubiquitin-like modifier) enzyme SENP1, leading to a consequent increase in
      protein SUMOylation. Overexpression of the catalytic domain of SENP1 prevents
      this scaling effect, and we identify Arc as a SUMO substrate involved in the
      tetrodotoxin-induced increase in AMPAR surface expression. Thus, protein
      SUMOylation plays an important and previously unsuspected role in synaptic
      trafficking of AMPARs that underlies homeostatic scaling.

PMID- 22582392
TI  - Regulatory domain determinants that control PKD1 activity.
AB  - The canonical pathway for protein kinase D1 (PKD1) activation by growth factor
      receptors involves diacylglycerol binding to the C1 domain and protein kinase C
      dependent phosphorylation at the activation loop. PKD1 then autophosphorylates at
      Ser(916), a modification frequently used as a surrogate marker of PKD1 activity.
      PKD1 also is cleaved by caspase-3 at a site in the C1-PH interdomain during
      apoptosis; the functional consequences of this cleavage event remain uncertain.
      This study shows that PKD1-Delta1-321 (an N-terminal deletion mutant lacking the
      C1 domain and flanking sequence that models the catalytic fragment that
      accumulates during apoptosis) and PKD1-CD (the isolated catalytic domain) display
      high basal Ser(916) autocatalytic activity and robust activity toward CREBtide (a
      peptide substrate) but little to no activation loop autophosphorylation and no
      associated activity toward protein substrates, such as cAMP-response element
      binding protein and cardiac troponin I. In contrast, PKD1-DeltaPH (a PH domain
      deletion mutant) is recovered as a constitutively active enzyme, with high basal
      autocatalytic activity and high basal activity toward peptide and protein
      substrates. These results indicate that individual regions in the regulatory
      domain act in a distinct manner to control PKD1 activity. Finally, cell-based
      studies show that PKD1-Delta1-321 does not substitute for WT-PKD1 as an in vivo
      activator of cAMP-response element binding protein and ERK phosphorylation.
      Proteolytic events that remove the C1 domain (but not the autoinhibitory PH
      domain) limit maximal PKD1 activity toward physiologically relevant protein
      substrates and lead to a defect in PKD1-dependent cellular responses.

PMID- 22582391
TI  - Zinc metalloproteinase ProA directly activates Legionella pneumophila PlaC
      glycerophospholipid:cholesterol acyltransferase.
AB  - Enzymes secreted by Legionella pneumophila, such as phospholipases A (PLAs) and
      glycerophospholipid:cholesterol acyltransferases (GCATs), may target host cell
      lipids and therefore contribute to the establishment of Legionnaires disease. L.
      pneumophila possesses three proteins, PlaA, PlaC, and PlaD, belonging to the GDSL
      family of lipases/acyltransferases. We have shown previously that PlaC is the
      major GCAT secreted by L. pneumophila and that the zinc metalloproteinase ProA is
      essential for GCAT activity. Here we characterized the mode of PlaC GCAT
      activation and determined that ProA directly processes PlaC. We further found
      that not only cholesterol but also ergosterol present in protozoa was
      palmitoylated by PlaC. Such ester formations were not induced by either PlaA or
      PlaD. PlaD was shown here to possess lysophospholipase A activity, and
      interestingly, all three GDSL enzymes transferred short chain fatty acids to
      sterols. The three single putative catalytic amino acids (Ser-37, Asp-398, and
      His-401) proved essential for all PlaC-associated PLA, lysophospholipase A, and
      GCAT activities. A further four cysteine residues are important for the PLA/GCAT
      activities as well as their oxidized state, and we therefore conclude that PlaC
      likely forms at least one disulfide loop. Analysis of cleavage site and loop
      deletion mutants suggested that for GCAT activation deletion of several amino
      acids within the loop is necessary rather than cleavage at a single site. Our
      data therefore suggest a novel enzyme inhibition/activation mechanism where a
      disulfide loop inhibits PlaC GCAT activity until the protein is exported to the
      external space where it is ProA-activated.

PMID- 22582393
TI  - Regulation of protein kinase C inactivation by Fas-associated protein with death
      domain.
AB  - Protein kinase C (PKC) plays important roles in diverse cellular processes. PKC
      has been implicated in regulating Fas-associated protein with death domain
      (FADD), an important adaptor protein involved in regulating death receptor
      mediated apoptosis. FADD also plays an important role in non-apoptosis processes.
      The functional interaction of PKC and FADD in non-apoptotic processes has not
      been examined. In this study, we show that FADD is involved in maintaining the
      phosphorylation of the turn motif and hydrophobic motif in the activated
      conventional PKC (cPKC). A phosphoryl-mimicking mutation (S191D) in FADD (FADD-D)
      abolished the function of FADD in the facilitation of the turn motif and
      hydrophobic motif dephosphorylation of cPKC, suggesting that phosphorylation of
      Ser-191 negatively regulates FADD. We show that FADD interacts with PP2A, which
      is a major phosphatase involved in dephosphorylation of activated cPKC and FADD
      deficiency abolished PP2A mediated dephosphorylation of cPKC. We show that FADD
      deficiency leads to increased stability and activity of cPKC, which, in turn,
      promotes cytoskeleton reorganization, cell motility, and chemotaxis.
      Collectively, these results reveal a novel function of FADD in a non-apoptotic
      process by modulating cPKC dephosphorylation, stability, and signaling
      termination.

PMID- 22582394
TI  - HER-2/neu-mediated down-regulation of biglycan associated with altered growth
      properties.
AB  - The extracellular matrix protein biglycan (Bgn) is a leucine-rich proteoglycan
      that is involved in the matrix assembly, cellular migration and adhesion, cell
      growth, and apoptosis. Although a distinct expression of Bgn was found in a
      number of human tumors, the role of this protein in the initiation and/or
      maintenance of neoplastic transformation has not been studied in detail. Using an
      in vitro model of oncogenic transformation, a down-regulation of Bgn expression
      as well as an altered secretion of different Bgn isoforms was found both in
      murine and human HER-2/neu oncogene-transformed cells when compared with HER
      2/neu(-) cells. This was associated with a reduced growth, wound closure, and
      migration capacity. Vice versa, silencing of Bgn in HER-2/neu(-) fibroblasts
      increased the growth rate and migration capacity of these cells. Bgn expression
      was neither modulated in HER-2/neu(+) cells by transforming growth factor-beta(1)
      nor by inhibition of the phosphoinositol 3-kinase and MAP kinase pathways. In
      contrast, inhibition of the protein kinase C (PKC) pathway led to the
      reconstitution of Bgn expression. In particular, the PKC target protein cAMP
      response element binding protein (CREB) is a major regulator of Bgn expression as
      the silencing of CREB by RNA interference was accompanied by ~5000-fold increase
      in Bgn-mRNA expression in HER-2/neu(+) cells. Thus, Bgn inhibits the major
      properties of HER-2/neu-transformed cells, which is inversely modulated by the
      PKC signaling cascade.

PMID- 22582395
TI  - Regulatory factor X1-induced down-regulation of transforming growth factor beta2
      transcription in human neuroblastoma cells.
AB  - Regulatory factor X (RFX) proteins are transcription factors. Seven mammalian RFX
      proteins have been identified. RFX1 is the prototype RFX. However, its biological
      functions are not known. Here, RFX1 overexpression reduced fetal bovine serum
      stimulated proliferation of SH-SY5Y cells, a human neuroblastoma cell line. This
      inhibition is associated with decreased transforming growth factor beta2
      (TGFbeta2) and phospho-extracellular signal-regulated kinase (ERK). Exogenous
      TGFbeta2 increased cell proliferation and phospho-ERK in cells overexpressing
      RFX1. An anti-TGFbeta2 antibody and PD98059, an ERK activation inhibitor,
      inhibited SH-SY5Y cell proliferation. TGFbeta2 promoter activity was decreased in
      cells overexpressing RFX1. Chromosome immunoprecipitation assay showed that RFX1
      bound the TGFbeta2 promoter. RFX1 down-regulation increased TGFbeta2 in SH-SY5Y
      and HCN-1A cells, a normal human neuronal cell line. More importantly, TGFbeta2
      concentrations were negatively correlated with RFX1 levels in human
      medulloblastoma tissues with a R(2) of 0.464. These results suggest that RFX1
      reduces cell proliferation through inhibiting the TGFbeta2-ERK signaling pathway.
      RFX1 blocks TGFbeta2 expression through its direct action on TGFbeta2
      transcription. This effect also appears in human brain tumor tissues. Because
      TGFbeta is known to be involved in cancer development, our results provide
      initial evidence to suggest that RFX1 may play an important role in human tumor
      biology.

PMID- 22582396
TI  - Binding of phytopolyphenol piceatannol disrupts beta/gamma subunit interactions
      and rate-limiting step of steady-state rotational catalysis in Escherichia coli
      F1-ATPase.
AB  - In observations of single molecule behavior under V(max) conditions with minimal
      load, the F(1) sector of the ATP synthase (F-ATPase) rotates through continuous
      cycles of catalytic dwells (~0.2 ms) and 120 degrees  rotation steps (~0.6 ms).
      We previously established that the rate-limiting transition step occurs during
      the catalytic dwell at the initiation of the 120 degrees  rotation. Here, we use
      the phytopolyphenol, piceatannol, which binds to a pocket formed by contributions
      from alpha and beta stator subunits and the carboxyl-terminal region of the rotor
      gamma subunit. Piceatannol did not interfere with the movement through the 120
      degrees  rotation step, but caused increased duration of the catalytic dwell. The
      duration time of the intrinsic inhibited state of F(1) also became significantly
      longer with piceatannol. All of the beads rotated at a lower rate in the presence
      of saturating piceatannol, indicating that the inhibitor stays bound throughout
      the rotational catalytic cycle. The Arrhenius plot of the temperature dependence
      of the reciprocal of the duration of the catalytic dwell (catalytic rate)
      indicated significantly increased activation energy of the rate-limiting step to
      trigger the 120 degrees  rotation. The activation energy was further increased by
      combination of piceatannol and substitution of gamma subunit Met(23) with Lys,
      indicating that the inhibitor and the beta/gamma interface mutation affect the
      same transition step, even though they perturb physically separated rotor-stator
      interactions.

PMID- 22582412
TI  - [Collateral damage].

PMID- 22582397
TI  - The Q motif of Fanconi anemia group J protein (FANCJ) DNA helicase regulates its
      dimerization, DNA binding, and DNA repair function.
AB  - The Q motif, conserved in a number of RNA and DNA helicases, is proposed to be
      important for ATP binding based on structural data, but its precise biochemical
      functions are less certain. FANCJ encodes a Q motif DEAH box DNA helicase
      implicated in Fanconi anemia and breast cancer. A Q25A mutation of the invariant
      glutamine in the Q motif abolished its ability to complement cisplatin or
      telomestatin sensitivity of a fancj null cell line and exerted a dominant
      negative effect. Biochemical characterization of the purified recombinant FANCJ
      Q25A protein showed that the mutation disabled FANCJ helicase activity and the
      ability to disrupt protein-DNA interactions. FANCJ-Q25A showed impaired DNA
      binding and ATPase activity but displayed ATP binding and temperature-induced
      unfolding transition similar to FANCJ-WT. Size exclusion chromatography and
      sedimentation velocity analyses revealed that FANCJ-WT existed as molecular
      weight species corresponding to a monomer and a dimer, and the dimeric form
      displayed a higher specific activity for ATPase and helicase, as well as greater
      DNA binding. In contrast, FANCJ-Q25A existed only as a monomer, devoid of
      helicase activity. Thus, the Q motif is essential for FANCJ enzymatic activity in
      vitro and DNA repair function in vivo.

PMID- 22582414
TI  - Museums [from the editor].

PMID- 22582413
TI  - Image of the month: Cystic variant of pancreatic acinar cell carcinoma.

PMID- 22582415
TI  - Guest editorial: special issue on interventional imaging.

PMID- 22582449
TI  - [Programs of cultural and national autonomy: their    making and variations].

PMID- 22582418
TI  - A single vesicle-vesicle fusion assay for in vitro studies of SNAREs and
      accessory proteins.
AB  - SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor)
      proteins are a highly regulated class of membrane proteins that drive the
      efficient merger of two distinct lipid bilayers into one interconnected
      structure. This protocol describes our fluorescence resonance energy transfer
      (FRET)-based single vesicle-vesicle fusion assays for SNAREs and accessory
      proteins. Both lipid-mixing (with FRET pairs acting as lipophilic dyes in the
      membranes) and content-mixing assays (with FRET pairs present on a DNA hairpin
      that becomes linear via hybridization to a complementary DNA) are described.
      These assays can be used to detect substages such as docking, hemifusion, and
      pore expansion and full fusion. The details of flow cell preparation, protein
      reconstituted vesicle preparation, data acquisition and analysis are described.
      These assays can be used to study the roles of various SNARE proteins, accessory
      proteins and effects of different lipid compositions on specific fusion steps.
      The total time required to finish one round of this protocol is 3-6 d.

PMID- 22582450
TI  - Innovative strategies to help Consumer Operated and Oriented Plans (CO-OPs)
      compete in new insurance marketplaces.
AB  - The Affordable Care Act paves the way for groups to develop innovative,
      affordable health insurance and care options known as Consumer Operated and
      Oriented Plans (CO-OPs). These CO-OPs will be nonprofit, consumer-controlled
      entities that are designed to serve individuals and small businesses, especially
      in noncompetitive markets. The CO-OP provision was included in the Affordable
      Care Act to address the lack of affordable health plan alternatives in many state
      and regional markets and to counter a trend toward market concentration. Despite
      their promise, CO-OPs face a number of business challenges that go beyond typical
      start-up hurdles. This issue brief lays out a number of innovative strategies CO
      OP organizers are developing to increase the odds of long-term sustainability and
      economic success. These strategies--aimed at building market share, creating
      integrated provider networks, and achieving cost savings through payment reform-
      could establish CO-OPs as a viable new entrant in the health care field.

PMID- 22582451
TI  - Gaps in health insurance: why so many Americans experience breaks in coverage and
      how the Affordable Care Act will help: findings from the Commonwealth Fund Health
      Insurance Tracking Survey of U.S. Adults, 2011.
AB  - The Commonwealth Fund Health Insurance Tracking Survey of U.S. Adults finds that
      one-quarter of adults ages 19 to 64 experienced a gap in their health insurance
      in 2011, with a majority remaining uninsured for one year or more. Losing or
      changing jobs was the primary reason people experienced a gap. Compared with
      adults who had continuous coverage, those who experienced gaps were less likely
      to have a regular doctor and less likely to be up to date with recommended
      preventive care tests, with rates declining as the length of the coverage gap
      increases. Early provisions of the Affordable Care Act are already helping bridge
      gaps in coverage among young adults and people with preexisting conditions.
      Beginning in 2014, new affordable health insurance options through Medicaid and
      state insurance exchanges will enable adults and their families to remain insured
      even in the face of job changes and other life disruptions.

PMID- 22582452
TI  - Explaining high health care spending in the United States: an international
      comparison of supply, utilization, prices, and quality.
AB  - This analysis uses data from the Organization for Economic Cooperation and
      Development and other sources to compare health care spending, supply,
      utilization, prices, and quality in 13 industrialized countries: Australia,
      Canada, Denmark, France, Germany, Japan, the Netherlands, New Zealand, Norway,
      Sweden, Switzerland, the United Kingdom, and the United States. The U.S. spends
      far more on health care than any other country. However this high spending cannot
      be attributed to higher income, an older population, or greater supply or
      utilization of hospitals and doctors. Instead, the findings suggest the higher
      spending is more likely due to higher prices and perhaps more readily accessible
      technology and greater obesity. Health care quality in the U.S. varies and is not
      notably superior to the far less expensive systems in the other study countries.
      Of the countries studied, Japan has the lowest health spending, which it achieves
      primarily through aggressive price regulation.

PMID- 22582453
TI  - [The social security system for orphans in the postwar    period, 1945-55].

PMID- 22582454
TI  - [The 1802 uprising of the Indians in the history of    Russian America].

PMID- 22582456
TI  - [The ethnic factor in the internal Afghan conflict: a    historical analysis].

PMID- 22582457
TI  - [The growth of megalopolises as one form of contemporary urbanization].

PMID- 22582462
TI  - Death colonized: historical adult mortality in Rhodesia (Zimbabwe).

PMID- 22582463
TI  - Zimbabwe: pre-colonial history, demographic disaster and the university.

PMID- 22582464
TI  - [The wills of Dalmatian patricians in Venice,    15th-18th centuries].

PMID- 22582465
TI  - Untruths about palliative care.

PMID- 22582466
TI  - Factors associated with medical cost among patients with terminal cancer in
      hospice units.
AB  - This study identified factors associated with higher medical costs for patients
      with terminal cancer in hospice units in order to develop a daily payment system
      for hospice services within Korea's National Health Insurance (NHI) program.
      Through chart reviews conducted by staff nurses, medical information and costs
      were obtained for 274 patients with terminal cancer in 20 hospice units in
      October 2007. The daily medical cost per patient was calculated based on the fee
      for-service scheme. The characteristics of the hospice units were examined by
      means of a semistructured questionnaire administered to hospice unit
      coordinators. Higher daily costs were associated with general hospital-based
      hospice units (as compared with free-standing units: p<0.01), low Palliative
      Performance Scale scores (PPS<50, p<0.05), and the presence of fever (p<0.01). In
      multivariate analysis, hospice unit type was found to be the factor most strongly
      associated with medical cost. A hospice payment system based on patient
      characteristics should be thoroughly considered.

PMID- 22582467
TI  - Evaluation of frequency of clinical symptoms and signs within six months prior to
      death in patients with advanced solid cancers.
AB  - This retrospective study documented the frequency of the clinical symptoms and
      signs that increase in advanced cancer patients as they move toward death in
      order to create a sum score and correlate it with survival. Of 572 adult patients
      who were treated in four selected hospitals and who died in 1998 and 1999, data
      at six, three, and one month(s) prior to death was available for 257. The results
      showed that the number of symptoms and certain clinical findings accelerated
      toward death, increasing the sum score. Younger patients obtained higher sum
      scores at one month prior to death than did elderly ones (p=0.014); this suggests
      that elderly patients die at a point where they show less worsening in their
      clinical condition than do younger patients. The score was independent of cancer
      type or gender. The results of this analysis provide data for further development
      of a clinical tool to predict long-term survival in palliative care settings.

PMID- 22582468
TI  - End-of-life discussions and advance care planning for children on long-term
      assisted ventilation with life-limiting conditions.
AB  - Families of children with life-limiting conditions who are on long-term assisted
      ventilation need to undertake end-of-life advance care planning (ACP) in order to
      align their goals and values with the inevitability of their child's condition
      and the risks it entails. To discuss how best to conduct ACP in this population,
      we performed a retrospective analysis of end-of-life discussions involving our
      deceased ventilator-assisted patients between 1987 and 2009. A total of 34 (72
      percent) of 47 study patients were the subject of these discussions; many
      discussions occurred after acute deterioration. They resulted in directives to
      forgo or limit interventions for 21 children (45 percent). We surmise that many
      families were hesitant to discuss end-of-life issues during periods of relative
      stability. By offering anticipatory guidance and encouraging contemplation of
      patients' goals both in times of stability and during worsening illness, health
      care providers can better engage patients' families in ACP. As the child's
      condition progresses, the emphasis can be recalibrated. How families respond to
      such encouragement can also serve as a gauge of their willingness to pursue ACP.

PMID- 22582469
TI  - Opportunities for quality improvement in bereavement care at a children's
      hospital: assessment of interdisciplinary staff perspectives.
AB  - This study examined the current state of bereavement care at a university-based
      children's hospital from the perspective of the interdisciplinary staff. In all,
      60 staff members from multiple disciplines participated in in-depth interviews.
      In at least two-thirds of the interviews, issues related to the bereavement
      experience of both staff and families emerged and were consistently identified.
      Themes included: disparities in bereavement care based on relationship factors;
      logistics of time and space; geographical distances; the different cultures and
      languages of families; continuity in family follow-up; needs of siblings and
      other family members; staff communication, cooperation, and care coordination;
      staff suffering; and education, mentoring, and support for staff. This evidence
      based needs assessment furnishes an empirical basis for the design and
      implementation of bereavement services for both families and staff. It can serve
      as a template for evaluation at other children's hospitals and thus contribute to
      the sound and creative development of the field of pediatric palliative care.

PMID- 22582470
TI  - Paramedics' perceptions of their role in palliative care: analysis of focus group
      transcripts.
AB  - Paramedics play an important role in out-of-hospital health care. They provide
      unscheduled care, assisting both patients with minor injuries and those
      experiencing life-threatening emergencies. Increasingly, paramedics are called on
      to manage chronic and complex health needs, including symptom relief for patients
      at the end of life. However, paramedics may not be well prepared to offer
      palliative care, as practice guidelines and education tend to focus on the
      management of acute medical emergencies and major trauma. Emergency medical
      services that employ paramedics rarely have practice guidelines or protocols that
      deal specifically with palliative care.

PMID- 22582471
TI  - An integrated view of suffering in palliative care.

PMID- 22582472
TI  - Living with the twin mysteries of prognostication and death awareness.

PMID- 22582473
TI  - Development of the Northern Plains Native Family Cancer Caregiver Education
      Program.

PMID- 22582474
TI  - Severe cannabinoid intoxication in a patient with non-small-cell lung cancer.

PMID- 22582475
TI  - Lessons in death and dying on an East African surgical ward.

PMID- 22582476
TI  - A descriptive analysis of 188 liver transplant patient visits to an emergency
      department.
AB  - BACKGROUND: The aim of the study is to seek the causes of application, the
      demographic and clinical characteristics of liver transplant patients and to
      share the experiences of our Emergency Department. MATERIALS AND METHODS: One
      hundred eighty-eight Emergency Department visits of ninety patients who underwent
      liver transplant operations between 2002 and 2009 were evaluated retrospectively.
      RESULTS: The patients applied to the Emergency Department with the complaints of
      fever 28.2% and abdominal pain 30.9%. It was detected that the final diagnosis of
      52.4% of the patient visits was associated with the gastrointestinal system. It
      was observed that the most common treatment was drug therapy by 45.2% and that
      antibiotics treatment was the most applied method in drug treatment. Alanine
      aminotransferase (ALT) median value of hospitalized patients (45.5 U/L) is
      significantly higher than that of discharged patients (35 U/L) (p = 0.04). From
      the records of the patients, positive correlations between the length of
      hospitalization and levels of total bilirubin, direct bilirubin, ALT and fever
      during the visit were detected (p = 0.001, p < 0.001, p = 0.01, p = 0.01,
      respectively). CONCLUSIONS: Most frequently liver transplant recipients visited
      the Emergency Departments with the complaints of fever and abdominal pain. The
      diagnosis was generally associated with gastrointestinal system disorders. The
      percentage of hospitalization was high and the length of stay at the hospital was
      long. The treatment of these patients required a multidisciplinary approach and
      antibiotics constituted the most used drug treatment. Also, fever and liver
      function tests examined at the time of admittance to the Emergency Department
      affected the length of hospitalization.

PMID- 22582477
TI  - Reduced performance of Troponin T for acute coronary syndromes diagnosis in the
      elderly and very elderly patients: a retrospective study of 2688 patients.
AB  - STUDY OBJECTIVE: We evaluated the performance of Troponin T (cTnT) for acute
      coronary syndrome (ACS) diagnosis in elder compared to younger patients.
      MATERIALS AND METHODS: We retrospectively evaluated 2688 patients admitted to our
      Emergency Department for suspected ACS. All patients received ECG, serum
      creatinine determination, and serial cTnT samplings. Patients were considered
      positive for cTnT if they had a cTnT above our reference standard (>0.03
      microg/L) in any determination obtained within 6 hours from admission. ACS
      diagnosis, either acute myocardial infarction or unstable angina, was based on
      reviewed data and discharge diagnosis hospital. Patients were divided in three
      groups according to age: <65-years-old, elders > or =65 and <80 years, and very
      elders > or =80 years. CTnT diagnostic accuracy for ACS was compared in these
      three groups in patients <65 years. RESULTS: Two thousands six and hundred eighty
      eight patients (35.3% female) were enrolled in this study. 1087 patients (40.4%)
      were <65 years old, while 1205 patients (44.8%) were >or =65 and <80 years, and
      396 patients (14.8%) were > or =80 years. The overall sensitivity of cTnT for ACS
      diagnosis was 0.57 (CI 95% 0.54-0.60) with a specificity of 0.71 (CI 95% 0.69
      0.73). In older cohorts cTnT showed a reduced performance for ACS diagnosis. Area
      under the receiver operating characteristic curve of abnormal cTnT for ACS was
      0.70 (0.66-0.73) in <65 years, 0.61 (95% CI 0.60-0.66) in > or =65 and <80 years,
      and 0.59 (0.53-0.65) in > or =80 years. CONCLUSION: Compared to younger patients
      cTnT showed a reduced performance for ACS diagnosis in elders > or =65 and <80
      years; cTnT performance was further reduced in patients > or =80 years.

PMID- 22582478
TI  - Atrioventricular plane displacement: does it predict in-hospital outcome after
      acute myocardial infarction?
AB  - BACKGROUND AND OBJECTIVES: Atrioventricular plane displacement is a well-accepted
      method for assessment of left ventricular systolic function. We explored the
      ability of atrioventricular plane displacement to predict inhospital outcome in
      patients with acute ST-elevation myocardial infarction. MATERIALS AND METHODS:
      Ninety three patients with acute ST-elevation myocardial infarction were
      prospectively included. Each patient underwent trans-thoracic echocardiography
      for measurement of the ejection fraction by the Simpson's method.
      Atrioventricular plane displacement was measured from the apical views, assessed
      in four different regions, namely, the septal, lateral, anterior and inferior
      ones, and the mean value was calculated. We used a cutoff value to classify
      patients into a group with atrioventricular plane displacement <10 mm and another
      with atrioventricular plane displacement > or=10 mm. Similarly, patients were
      classified into those with ejection fraction <40% and others with ejection
      fraction a 40%. All patients were followed-up during their in-hospital stay for
      the occurrence of major adverse cardiac events, namely, death, heart failure,
      complex ventricular arrhythmias, post-infarction angina, or mechanical
      complications. RESULTS: During the follow-up period (3 +/- 1.5 days), major
      adverse cardiac events occurred in 16 (72.7%) patients with atrioventricular
      plane displacement <10 mm, and in 6(8.5%) patients with atrioventricular plane
      displacement > or =10 mm, p < 0.01. An atrioventricular plane displacement below
      10 mm was able to predict the occurrence of major events with a sensitivity
      72.7%, specificity 91.5%, negative predictive value (NPV) 91.5%, positive
      predictive value (PVP) 72.7%. Similarly, an ejection fraction below 40% predicted
      the occurrence of major events with a sensitivity 72.7%, specificity 90.1%, NPV
      91.4%, PVP 69.6%. We found a strong correlation between an atrioventricular plane
      displacement < 10 mm, and an ejection fraction <40%, p < 0.01. CONCLUSION: Left
      atrioventricular plane displacement below 10 mm, can adequately predict the
      occurrence of in-hospital major adverse cardiac events after acute ST-elevation
      myocardial infarction, with a high correlation with ejection fraction below 40%.

PMID- 22582479
TI  - Acute myocardial infarction during the early postpartum period successfully
      treated with tirofiban.
AB  - Acute myocardial infarction (AMI) during the early postpartum period is rare but
      may be associated with poor maternal outcome. We report an inferior AMI in 30
      year-old woman with mitral valve replacement during early postpartum period
      successfully treated with tirofiban. For a patient that has got AMI due to
      massive thrombus and that is not suitable for percutaneous coronary intervention
      and has got contraindication to thrombolytic therapy, glikoprotein IIb-IIIa
      inhibitor (tirofiban) infusion must be kept in mind.

PMID- 22582480
TI  - QT dispersion in carbon monoxide poisoning.
AB  - BACKGROUND: Carbon monoxide (CO) poisoning are serious health problems, and
      effect of reducing the blood's oxygen carrying capacity. Deaths due to CO
      poisoning are mostly related to myocardial injury and central nervous system
      pathologies. AIM: The objective of this study was to determine the relationship
      between carbon monoxide intoxication, QT dispersion, and cardiac markers.
      MATERIALS AND METHODS: Patients with possible CO intoxication symptoms were
      evaluated to be eligible for the study. Patients' demographic data,
      carboxyhemoglobin levels, cardiac markers and QT interval measurements were
      recorded to the study form. RESULTS: A total of 127 patients (79 CO intoxicated
      and 48 controls) were included into the study with a mean age of 38.6 +/- 14.1
      years and 62.2% of them were female. Average levels of patient's
      carboxyhemoglobin were 21.3 +/- 9. QT dispersion (39.0 +/- 10.8 vs 24.4 +/- 6.2;
      p < 0.001) and corrected QT dispersion (46.2 +/- 14.7 vs. 25.3 +/- 6.2; p <
      0.001) were longer than the control group. Both QT dispersion (39.0 +/- 10.8 vs.
      23.6 +/- 7.0; p < 0.001) or corrected QT dispersion (46.2 +/- 14.7 vs. 27.1 +/-
      8.7; p < 0.001) were also decreased after one week later from the admission.
      CONCLUSION: Carbon monoxide intoxication is related to increased QT dispersion.
      Emergency physicians should measure QT dispersion in CO intoxicated patients in
      order to predict the electrical instability in myocardium and future adverse
      events.

PMID- 22582481
TI  - Left kidney: an unusual site of cocaine-related renal infarction. A case report.
AB  - Acute renal infarction is a well known, although relatively unfrequent, cause of
      flank pain resistant to administration of spasmolytic and nonsteroidal anti
      inflammatory drugs. We present an original case of a 41-year-old man, complaining
      of acute severe left flank pain, resistant to common analgesic therapy, who was
      diagnosed of segmental renal infarction of a branch of left renal artery.
      Pathophysiology of renal damage in cocaine users is multifactorial, and it has
      been postulated that the right kidney was more prone to ischaemia. Left kidney
      represents an extremely unusual site of cocaine-related renal infarction.

PMID- 22582482
TI  - Tramadol-induced seizures and trauma.
AB  - BACKGROUND AND OBJECTIVES: To determine the prevalence, type and site of the
      injuries due to tramadol-induced seizures in the patients who had referred after
      its overdose or use of its therapeutic dose. MATERIAL AND METHODS: All patients
      referring to Loghman Hakim Poison Hospital (February 2009 to April 2010) due to
      tramadol-induced seizures were included. The patients' data including age,
      gender, ingested dose by history, route of exposure, manner of poisoning,
      previous history of suicidal attempts, previous history of drug or substance
      abuse, history of tramadol abuse, type of the seizure, number of episodes of
      seizure before presentation or after admission, site of the trauma, and type of
      injury were recorded. RESULTS: A total of 232 patients were included in the
      study. Of them, 185 (79.7%) had referred within the first 6 hours after
      ingestion. The mean dose ingested by the history was 1416 +/- 1124 mg. History of
      tramadol abuse was positive in 114 (49.1%) patients. Seizure episodes had
      occurred once in 207 (89.2%), twice in 21 (9.1%), and three times in 4 (1.7%)
      patients. The prevalence of trauma was 24.6% (in 57 patients) with the most
      frequent site of trauma to the face (9.5%) followed by shoulder (4.3%), head
      (3%), trunk (1.7%), and upper extremities (1.3%). No statistically significant
      difference was found between patients with and without trauma associated with
      tramadol-induced seizures in terms of age, gender, ingested dose by history,
      positive history of addiction to other opioids, and number of episodes of
      seizure. CONCLUSIONS: The only serious injury associated with this type of
      seizure was the head injury, present in approximately 1% of the patients.

PMID- 22582483
TI  - Lipid emulsion improves Glasgow coma scale and decreases blood glucose level in
      the setting of acute non-local anesthetic drug poisoning--a randomized controlled
      trial.
AB  - BACKGROUND: To date, no study has been performed to evaluate the antidotal effect
      of intravenous lipid emulsion on the poisoned patients' level of consciousness
      and routine metabolic profile tests in non-local anesthetic drug overdose.
      OBJECTIVES: Our aim was to evaluate the effect of intravenous intralipid
      administration as an antidote on the poisoned patients' Glasgow Coma Scale (GCS),
      hemodynamic parameters, arterial blood gas analysis, and routine metabolic
      profile tests (i.e., urea, glucose, sodium, and potassium) in the setting of non
      local anesthetic drug overdose. MATERIAL AND METHODS: In this randomized
      controlled trial, a total of 30 patients with non-local anesthetic drug
      intoxication were enrolled and randomly assigned into case (n=15) and control
      (n=15) groups. In the case group, all patients received 10 cc/kg intralipid 10%
      infusion. The patients in the control group just received the supportive care.
      Patients' demographic and clinical characteristics and results of their
      laboratory tests were evaluated at presentation and 6 hours after that. RESULTS:
      Mean age was 23 +/- 5 and 28 +/- 11 years in cases and controls, respectively.
      There were no significant statistical differences between these two groups
      regarding age, gender, elapsed time between intubation and extubation, and need
      for intubation and/or mechanical ventilation (p = 0.70 and p = 1.00,
      respectively). Also, systolic blood pressure, pulse rate, mean rate pressure
      product, respiratory rate, results of arterial blood gas analyses, serum sodium,
      potassium, urea, and creatinine on presentation and six hours later were not
      statistically significantly different between the two study groups. However, a
      significant difference was found between the two groups in terms of GCS
      difference (p = 0.048) and blood glucose six hours after presentation (p = 0.04).
      CONCLUSIONS: In the setting of non-local anesthetic drug overdose, intravenous
      intralipid infusion can increase GCS and interestingly, decrease the blood
      glucose.

PMID- 22582484
TI  - Benefit of hemodialysis in carbamazepine intoxications with neurological
      complications.
AB  - AIM: It is aimed to share the fact that hemodialysis is also useful in
      carbamazepine intoxications with prominent neurological side effects in cases
      hemoperfusion is not available. PATIENTS AND METHOD: Files of 49 patients
      presenting our Emergency Room with a prediagnosis of carbamazepine intoxication
      were analyzed retrospectively. Demographic and laboratory data of patients were
      recorded on study form. Patients were divided into two groups as those applied
      hemodialysis (Group 1) and those not applied hemodialysis (Group 2). Group 1
      included 13 patients while group 2 did 36. RESULTS: Statistically significant
      differences were detected between groups in terms of heart rate, Glasgow Coma
      scale score, presence of convulsions, midriasis and blood carbamazepine levels at
      the time of presentation. It was observed that carbamazepine levels decreased by
      58% via hemodialysis in those receiving hemodialysis. DISCUSSION: Hemodialysis is
      simple, cheap, widespread and easier to apply compared to hemoperfusion. It has
      been shown that acute carbamazepine intoxication can be treated with low flow
      high activity standard hemodialysis and it is a good therapeutic option.

PMID- 22582485
TI  - Venous thrombosis in emergency department: diagnosis, treatment, and disposition.
AB  - AIM: The Authors describe diagnosis, treatment and therapy of deep venous
      thrombosis in Emergency Department following the last guidelines indications.
      DISCUSSION: Deep venous thrombosis of the legs, ranges from asymptomatic,
      incidentally discovered emboli to massive embolism causing immediate death.
      Chronic sequelae of venous thromboembolism (deep venous thrombosis and pulmonary
      embolism) include the post-thrombotic syndrome and chronic thromboembolic
      pulmonary hypertension. Acute pulmonary embolism may occur rapidly and
      unpredictably and may be difficult to diagnose. Diagnosis and treatment can
      reduce the risk of death, and appropriate primary prophylaxis is usually
      effective. Patients treated for acute pulmonary embolism appear to be more times
      as likely to die of recurrent thromboembolism in the next year.

PMID- 22582486
TI  - Chronic systemic inflammatory syndrome in patients with AECOPD presenting to
      emergency department.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the fourth cause of
      dead in the world. Because of high incidence of comorbidities in COPD patients,
      it has been proposed a new hypothesis that inscribe this disease in a complex
      contest named chronic systemic inflammatory syndrome (CSIS). Either COPD and the
      most common comorbidities responsible for its clinical and natural history, like
      hypertension, diabetes, coronary artery disease, heart failure, recognize a pro
      inflammatory state, marked, for example, by elevated C reactive protein (CRP).
      METHODS: 113 consecutive patients presenting to emergency department (ED) with
      acute exacerbated COPD were enrolled. They underwent to full medical history and
      physical examination. CRP was measured at ED arrival, discharge and at 1-6-12
      month follow up. CSIS was diagnosed according to specified criteria. RESULTS:
      CSIS was diagnosed in 84% patients. CRP was maximally increased at admission
      during the exacerbation, but didn't correlate with the severity of it. At
      discharge, CRP values were lowest; during follow up, CRP demonstrated a chaotic
      behavior growing up till 6 month without any correlation with new exacerbation
      events. At 1 year it decreased, never reaching normal values in the majority of
      our patients thus confirming the presence of a persistent inflammation in COPD.
      CONCLUSIONS: CSIS was diagnosed in 84% of our population demonstrating that COPD
      patients need to be approached in a multidisciplinary way.

PMID- 22582487
TI  - Elderly trauma: the two years experience of a university-affiliated emergency
      department.
AB  - OBJECTIVE: The elderly population is steadily increasing in the modern world. The
      aging of the population has led to an increase in geriatric trauma. Elderly
      trauma patients present unique challenges and face more significant obstacles in
      recovery compared to younger patients. This study is designed to determine the
      epidemiologic data of trauma in elderly patients and to contribute to the
      national trauma database. MATERIALS AND METHODS: We prospectively collected the
      data of trauma patients, aged 65 and older, presenting to our Emergency
      Department. Patients' data, including demographic data, diagnosis, prognosis,
      trauma scores [Glasgow coma scale (GCS), injury severity score (ISS)], mortality,
      body regions of injury and outcomes were analyzed. RESULTS: During the study
      period, 407 patients, of whom 63.9% were males and 36.1% females, were admitted
      to our Emergency Department. The mean age of, the patients was 73.14 +/- 7.14
      years. Falls (59%) accounted for the most common cause of injury. The mean GCS
      and mean ISS were 14.39 and 10.69, respectively. Trauma to extremities was the
      most frequent body region of injury (56.3%). A total of 149 patients were
      hospitalized. The mean hospital length of stay was 11.07 +/- 14 days. The
      mortality rate was found to be 6.4%. Head trauma was the most common cause in
      mortality. CONCLUSIONS: The risk of trauma in the elderly population is higher.
      As a result of the decrease in physiological reserve and lack of adaptation to
      trauma, elderly trauma patients require more aggressive management and a
      multidisciplinary approach. Further studies are needed for data of elderly trauma
      patients.

PMID- 22582488
TI  - The medical approaching to a pellet injury of the heart.
AB  - A 55-year-old man with multiple pellet injuries was brought to the Emergency
      room. In his physical examination, there were multiple wounds in face, neck,
      shoulders, arms, thorax and upper abdomen. The therapeutic options include
      pericardial drainage, conservative treatment, and surgical removal of the pellet.
      But, he was successfully managed with conservative medical treatment. This case
      showed that the treatment of heart injuries due to shotgun pellet should be
      individualized.

PMID- 22582489
TI  - A rare cause of syncope: cough.
AB  - BACKGROUND: Syncope is a transient loss of consciousness, associated with loss of
      postural tone, with spontaneous return to baseline neurologic function. Syncope
      is a common complaint in the emergency department. OBJECTIVES: Cough syncope
      occurs immediately after coughing. Cough syncope rapidly recovers in 1-2 second.
      Although cough syncope has been classified in vasovagal syncope, it may differ
      from pathogenetic mechanism. Physicians should be aware of this easily
      recognizable cough induced syncope. CASE REPORT: We present a 59-year-old obese
      man was referred for clinical evaluation because of recurrent syncope without
      seizures following coughing who developed cough syncope. CONCLUSIONS: Physicians
      should be aware of this easily recognizable cough induced syncope in all subjects
      admitted with syncope and should screen possible underlying sources of cough.

PMID- 22582490
TI  - Is the pepper spray a triggering factor in myocardial infarction? A case report.
AB  - Forty-year-old man was admitted to emergency department with complains of chest
      pain and dispnea after exposure the pepper gas that sprayed to environment during
      a social event. Physical examination and electrocardiogram was revealed acute
      myocardial infarction.

PMID- 22582491
TI  - Meeting the challenge of HIV diversity: strategies to mitigate the impact of HIV
      1 genetic heterogeneity on performance of nucleic acid testing assays.

PMID- 22582492
TI  - Study of changes in antioxidant enzymes status in diabetic post menopausal group
      of women suffering from cardiovascular complications.
AB  - BACKGROUND: In type 2 diabetic patients, persistence of hyperglycemia has been
      reported as a cause of increased production of oxygen free radicals (FR), which
      leads to oxidative stress (OS) and becomes the main factor for predisposition to
      the cardiovascular complications in diabetes. Diabetic postmenopausal women are
      prone to cardiovascular disease due to reduced production of estrogen which is a
      potent antioxidant and prevents oxidative stress (OS) in body. The study is being
      aimed to find out the status of antioxidant enzymes (AOEs) and malondialdehyde
      (MDA) in post-menopausal diabetic women. METHODS: The study was conducted with a
      total of 70 cases, which included 35 Type 2 diabetic post-menopausal females (45 
      60 years) with diabetic CVD complication as the study group and 35 age matched
      type 2 diabetic postmenopausal females without CVD complication. RESULTS: All
      diabetic post menopausal females with CVD had significantly higher levels of
      fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), total
      cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C),
      very low density lipoprotein cholesterol (VLDL-C), catalase (CAT), and
      malondialdehyde (MDA) and significantly lower levels of HDL-C, reduced
      glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), and
      superoxide dismutase (SOD) as compared to the levels of control subjects.
      CONCLUSIONS: During menopause, reduced production of estrogen causes
      hypertriglyceridemia, hypercholesterolemia, and hyperlipoproteinemia whose
      oxidation causes the accumulation of FR in the cell, which precipitates OS. Also,
      type 2 diabetic subjects with CVD poor glycemic control and impaired AOEs result
      in increased oxidative injury by failure of protective mechanisms, which further
      leads to oxidative stress.

PMID- 22582493
TI  - Increased urinary type II collagen C-telopeptide levels in Tunisian patients with
      knee osteoarthritis.
AB  - Osteoarthritis is characterized by a progressive degeneration of articular
      cartilage and loss of joint function. Clinical assessment of osteoarthritis is
      hampered by the lack of accurate measures of disease and disease progression,
      especially during the early stage. BACKGROUND: To investigate urinary C
      telopeptide fragments of type II collagen (CTX-II) levels in knee osteoarthritis
      in the Tunisian population compared with controls and to assess the association
      between this biomarker and radiological signs. METHODS: One hundred and twenty
      five female patients with knee osteoarthritis, aged 53.6 +/- 7.6 years with
      disease duration of 3.6 +/- 3.8 years and 57 female age-matched controls
      underwent Lyon Schuss X-ray exams. Two experienced readers independently measured
      the joint space width (JSW) and classified each knee for severity using the
      Kellgren/Lawrence scale. The urinary concentration of CTX-II was measured by a
      competitive ELISA. RESULTS: The levels of urinary CTX-II were significantly
      higher in knee osteoarthritis patients compared with controls (323.98 vs 218.04
      microg/mol creatinine). A weak and non significant association between the CTX-II
      level and JSW was found. The significant correlations were observed between age
      and CTX-II in both groups and between BMI and CTX-II only in controls.
      CONCLUSIONS: Analysis of CTX-II in urine samples of Tunisian patients with knee
      osteoarthritis provided a sensitive method to detect increased degradation of
      collagen type II in patients with osteoarthritis.

PMID- 22582494
TI  - Changes of proteases and proteinase inhibitors in androgen-dependent advanced
      prostate cancer patients with alpha2-macroglobulin deficiency.
AB  - BACKGROUND: It is thought that the quantitative imbalance between proteases and
      their inhibitors is a causative factor in invasion and metastasis of cancer
      cells. We previously reported on a number of androgen-dependent advanced prostate
      cancer (PCa) patients in which serum alpha2-macroglobulin (alpha2M) levels were
      markedly decreased to < 20 mg/dL (defined as alpha2M deficiency). Anti-androgen
      therapy is at first generally very effective for androgen-dependent advanced PCa,
      yielding survival benefits for most patients. In the present study, we evaluated
      serum levels of PSA, matrix metalloproteinases-2 (MMP-2), alpha2M, and alpha2
      plasmin inhibitor (alpha2PI) in advanced PCa patients with or without alpha2M
      deficiency in order to determine the clinical significance of these proteases and
      proteinase inhibitors for PCa progression. METHODS: In this study, 33 PCa
      patients were diagnosed at the Kitasato University Hospital and compared with 10
      healthy controls. PSA and MMP-2 levels were determined by enzyme immunoassay.
      Measurement of alpha2M was performed by laser-nephelometry, alpha2PI levels were
      determined by turbidimetric immunoassay. RESULTS: Serum levels of PSA and MMP-2
      in PCa patients with alpha2M deficiency were significantly higher than in
      patients not alpha2M-deficient. In contrast, serum levels of alpha2M and alpha2PI
      in these patients were significantly lower than in those not alpha2M-deficient.
      PSA and alpha2M levels showed an inverse relationship in androgen-dependent
      advanced PCa with alpha2M deficiency. CONCLUSIONS: Our findings indicate that the
      serum levels of these proteases and proteinase inhibitors, which are involved in
      the invasion and metastasis of PCa, may be indicators of PCa disease progression
      in addition to PSA levels.

PMID- 22582495
TI  - Association of insulin like growth factor-1 (IGF-1) and thyroid hormones in
      patients of acute leukemia.
AB  - BACKGROUND: For many years, several studies have demonstrated a relationship
      between insulin like growth factor-1 (IGF-1), thyroid hormones, and various
      malignancies. IGF-1 plays an important role in tumor proliferation in various
      malignancies. The relationship between IGF-1 and thyroid hormones is complex and
      not fully understood. Therefore we planned to evaluate the level of IGF-1 and
      thyroid hormones in patients of acute leukemia. METHODS: The present study
      included 25 patients with acute leukemia (Acute Myeloid Leukemia, n = 16; Acute
      Lymphoid Leukemia n = 9, mean age 28.16 years). 25 age and gender matched healthy
      individuals were taken as control (mean age 27.17 years). In all the subjects,
      serum IGF-1 was measured by enzyme linked immunosorbent assay (ELISA), serum
      total triiodothyronine (T3), thyroxine (T4) by radioimmunoassay (RIA), thyroid
      stimulating hormone (TSH) by immunoradiometric assay (IRMA), and free T3 (FT3)
      and free T4 (FT4) by chemilluminiscence. These tests were done before starting of
      chemotherapy and either 6 to 8 weeks after chemotherapy or at the time of
      remission, whichever was earlier. RESULTS: At the time of diagnosis, patients
      with acute leukemia showed a significantly increased level of IGF-1 as compared
      to controls (198.32 +/- 67.55 vs 160.64 +/- 45.96; p < 0.01). After 6 to 8 weeks
      of chemotherapy, patients with acute leukemia showed a significant decrease in
      the level of IGF-1 compared to the baseline values (198.32 +/- 67.55 vs 155.6 +/-
      45.96; p < 0.01). Though FT3, FT4, total T3, and total T4 values in these
      patients were within the normal range, these values were still significantly
      higher compared to controls. TSH levels were significantly lower in patients at
      the time of presentation and the levels increased after chemotherapy.
      CONCLUSIONS: The estimation of IGF-1 and thyroid hormones may be helpful in
      assessing the disease activity and predicting the response of chemotherapy.

PMID- 22582496
TI  - Interaction between selenium and arsenic in biological samples of psoriasis
      patients.
AB  - BACKGROUND: Psoriasis is a noncontagious, chronic skin disease affecting 1 in 50
      people worldwide. METHODS: The aim of present study was to compare the levels of
      arsenic (As) and selenium (Se) in samples of whole blood, urine, and scalp hair
      of 418 psoriasis patients of both genders aged 25 - 55 years. All psoriatic
      patients lived in the vicinity of a cement factory, and were categorized as mild,
      moderate, and severe. For comparison purposes, 395 healthy age-matched
      referent/control subjects, residents of industrial and non-industrial areas, were
      selected. The concentrations of essential trace and toxic elements were measured
      by electrothermal atomic absorption spectroscopy after microwave-assisted acid
      digestion. The validity and accuracy of methodology was checked by using
      certified reference materials (CRMs) and the conventional wet acid digestion
      method on the same CRMs and real samples. RESULTS: The observed mean values of As
      were significantly higher in scalp hair, blood, and urine samples of patients
      with mild and severe psoriasis as compared to the controls (p = 0.01 - 0.001),
      while the concentrations of Se were lower in the scalp hair and blood, but higher
      in the urine samples of psoriasis patients of all categories. CONCLUSIONS: The
      deficiency of Se in psoriatic patients may undoubtedly be caused by the toxic
      element exposures via dust produced by the cement factory.

PMID- 22582497
TI  - Differences in initial NSE levels in malignant and benign diseases of the
      thoracic wall.
AB  - BACKGROUND: Neuron-specific enolase (NSE) is widely used to follow-up patients
      with small cell lung cancer (SCLC). Since the NSE level can be influenced by a
      broad range of diseases and disorders a large study should be done to assess its
      level in various lung and non-lung tumors and benign diseases. METHODS: This
      research included 328 SCLC patients, 717 non-small cell lung cancer (NSCLC), 50
      other thoracic cancers such as tumors of the mediastinum and mesothelioma, 35 non
      pulmonary cancers like esophagus, breast and stomach cancer, 205 benign diseases,
      and 37 healthy individuals. The serum level of NSE was measured at initial
      diagnosis prior to therapy using electrochemiluminescence immunoassay (ECLIA,
      Roche Diagnostics). RESULTS: The high levels of NSE in SCLC differed
      significantly from all other groups. The results imply very good sensitivity of
      NSE in SCLC and good discriminatory power of NSE between SCLC and NSCLC.
      CONCLUSIONS: The NSE level in SCLC differs significantly from all other tested
      groups (p < 0.01). The highest values are seen in SCLC extensive disease. ROC
      curves revealed good discriminatory power of the initial NSE levels separating
      SCLC from other lung lesions. NSE can be used as a diagnostic tool for the early
      recognition of the neuroendocrine component of lung tumors and follow-up of SCLC
      patients.

PMID- 22582498
TI  - Relation of interleukin-6, TNF-alpha and interleukin-1alpha with disease activity
      and severity in juvenile idiopathic arthritis patients.
AB  - BACKGROUND: Evaluation of disease activity in children with Juvenile Idiopathic
      Arthritis (JIA) is primarily based on clinical examination and conventional
      parameters of inflammation. But, in daily clinical practice, these two findings
      often fail to be in accord, making therapeutic decisions difficult. The aim of
      our research was to evaluate the potential usefulness of IL-6, IL-1alpha and TNF
      alpha in monitoring disease activity and severity in JIA. METHODS: In a 2-year
      prospective study, IL-6, IL-1alpha, and TNF-alpha levels were measured using
      ELISA in 63 serum samples for 40 JIA patients. The control population consisted
      of 18 healthy children. The data were correlated with disease activity and
      severity (quantified with JADAS-27 composite score). RESULTS: The patients with
      active disease had greater IL-6 levels than did the patients with inactive
      disease [47.2 pg/mL (2 to 578.7) vs. 2.6 pg/mL (2 to 8.3); p = 0.002] and
      controls [47.2 pg/mL (2 to 578.7) vs. 2.25 pg/mL (2 to 4); p = 0.006].
      Differences between active disease and remission were also significant for every
      JIA subgroup. The cutoff value for IL-6 in the diagnosis of active disease
      obtained from the ROC curve analysis was 8.33 pg/mL. Levels of circulating IL-6
      were elevated in patients with severe and moderate disease activity (JADAS-27
      score > 10) compared with those of low disease activity (JADAS-27 score < or =
      10) [80.1 pg/mL (2 to 578.7) vs. 7.41 (2 to 69); p = 0.010]. We found no
      correlation of serum TNF-alpha and IL-1alpha levels with disease activity in our
      patients. The most elevated levels of serum TNF-alpha were found in patients
      during clinical remission with Etanercept. CONCLUSIONS: Serum IL-6 concentrations
      may serve as a biomarker of disease activity and severity in JIA, providing
      additional information in certain clinical situations with great discrepancy
      between clinical assessment and conventional laboratory tests. Upon treatment
      with Etanercept, although many JIA patients reached remission on medication, they
      developed increased circulating TNF-alpha levels.

PMID- 22582499
TI  - Association of BCL-2 polymorphism with the presence and severity of lumbar disc
      degeneration in the Chinese Han population.
AB  - BACKGROUND: Apoptosis is involved in the mechanism of lumbar disc disease (LDD).
      BCL-2 has been shown to play an anti-apoptosis role. The present study aims to
      examine the association of -938C > A polymorphism of the BCL-2 gene with the
      presence and severity of LDD in the Chinese Han population. METHODS: This study
      consisted of 325 patients with LDD and 236 normal controls. The grade of disc
      degeneration was determined according to Schneiderman's classification for MRI. 
      938C > A polymorphism was determined by "slow-down" polymerase chain reaction
      (PCR) method. RESULTS: The genotype frequency of -938C > A polymorphism was
      consistent with Hardy-Weinberg equilibrium (p = 0.136). Higher frequencies of 
      938CA and AA genotypes were found in patients with LDD compared with normal
      controls (p = 0.019). Furthermore, there were higher frequencies of the A allele
      in LDD patients than in normal controls (p = 0.005). Unconditional logistic
      regression analysis revealed that -938CA and AA genotypes were significantly
      associated with the presence of LDD compared with CC genotype (p = 0.041; OR
      1.449; 95% CI 1.015 - 2.067 and p = 0.015; OR 2.102; 95% CI 1.158 - 3.813,
      respectively). The A allele was significantly associated with the susceptibility
      to LDD compared with the C allele (p = 0.005; OR 1.436; 95% CI 1.113 - 1.851). In
      addition, -938CA and AA genotypes, as well as the A allele were found to be
      associated with the risk for higher degenerative grades of LDD compared with the
      CC genotype and C allele, respectively (p = 0.017 and p = 0.003, respectively).
      CONCLUSIONS: The -938C > A polymorphism of BCL-2 may be associated with the
      presence and severity of LDD in the Chinese Han population.

PMID- 22582500
TI  - Association of -592 region of IL-10 polymorphisms with asthma in south-eastern
      Iranian patients.
AB  - BACKGROUND: Cytokines are considered important factors for the pathogenesis of
      asthma as they play a key role in the regulation of immune responses. The aim of
      this study was to investigate the association between this disease and
      polymorphisms in the -592 region of the IL-10 gene. METHODS: This study was
      carried out on 100 asthmatic patients and 100 healthy controls. PCR-RFLP was
      applied to examine the polymorphisms in the -592 region of the IL-10 gene.
      RESULTS: Our results showed a significant difference between patients and
      controls in terms of genotypes and alleles of the -592 region of the IL-10 gene.
      CONCLUSIONS: According to our results, it can be concluded that the IL-10
      promoter polymorphisms may play a crucial role in the pathogenesis of asthma.

PMID- 22582501
TI  - Oxidative stress and antioxidant defense in patients with chronic hepatitis B.
AB  - BACKGROUND: Oxidative stress is defined as a disturbance of balance between free
      radicals and antioxidant defense system. This study investigated oxidative stress
      in patients with chronic hepatitis B. METHODS: Sixty nine patients with chronic
      hepatitis B admitted to the Department of the Infectious Diseases and Clinical
      Microbiology of Medical Faculty of Ondokuz Mayis University were enrolled into
      study. Twenty healthy persons were included as a control group. The study group
      was divided into three groups: healthy controls (group 1), chronic hepatitis B
      (group 2), and inactive hepatitis B carriers (group 3). Antioxidant status of
      plasma, including glutathione, glutathione peroxidase, vitamin E, and vitamin C
      levels were measured. Carbonyl and lipid peroxidation levels were measured as
      parameters of oxidative stress. RESULTS: Glutathione, glutathione peroxidase,
      vitamin E, and vitamin C levels were found to be significantly decreased in the
      chronic hepatitis B group when compared with the control group (9.5 vs. 13.8, p <
      0.05; 22.98 vs. 32.4, p < 0.05; 15.1 vs. 16.4, p < 0.05; 12.9 vs. 18.4, p < 0.05,
      respectively). Carbonyl and lipid peroxidation levels were significantly
      increased in the chronic hepatitis B group compared to controls (0.7 vs. 0.5, p <
      0.05; 2 vs. 0.7, p < 0.05, respectively). However, whereas the glutathione and
      carbonyl level correlation with HBV DNA levels were mild to moderate (glutathione
      vs. HBV DNA, r:-0.288, p < 0.05; carbonyl vs. HBV DNA, r:0.317, p < 0.05), the
      lipid peroxidation levels were strongly related with HBV DNA levels in chronic
      hepatitis B (r:0.545, p < 0.05). CONCLUSIONS: Oxidative stress was significantly
      increased in hepatitis B patients. Consequently, decreases were seen at the level
      of protective antioxidative parameters in the blood of these patients.

PMID- 22582502
TI  - Reference intervals for serum sex hormones in Han Chinese adult men from the
      Fangchenggang Area Male Health and Examination Survey.
AB  - BACKGROUND: The aim was to establish reference intervals for serum sex hormones
      in adult men in the Fangchenggang area of China. METHODS: Serum samples from
      1,191 healthy male subjects, aged 20 - 69 years, were collected from the
      Fangchenggang Area Male Health and Examination Survey (FAMHES). Total
      testosterone (T), estrogen (E2), luteinising hormone (LH), follicle-stimulating
      hormone (FSH), and sex hormone-binding globulin (SHBG) were measured by
      electrochemiluminescence immunoassay (Elecsys). Free testosterone (FTc) was
      calculated from the concentrations of T, SHBG, and albumin. RESULTS: The total
      nonparametric reference intervals for male sex hormones in our study were 12.6 -
      37.0 nmol/L for T, 0.24 - 0.69 nmol/L for FTc, 65.4 - 207.7 pmol/L for E2, 2.2 -
      11.6 IU/L for LH, 1.8 - 16.5 IU/L for FSH, and 18.2 - 95.1 nmol/L for SHBG. Age
      had a significant positive association with LH (r = 0.218), FSH (r = 0.427), and
      SHBG (r = 0.427) and a negative association with FTc (r = -0.383) and E2 (r = 
      0.098), but no significant association with T after adjustment for BMI. The age
      dependent reference intervals were also calculated. Higher T and FTc
      concentrations were found in men who smoke compared with non-smokers, while no
      significant differences were found in E2, LH, FSH, and SHBG. When stratified for
      the number of cigarettes smoked per day, we found that the distributions of serum
      T levels were significantly higher only in the smokers who smoked 11 or more
      cigarettes a day than the non-smokers. Unlike T, the distributions of serum FTc
      levels were significantly higher only in the smokers who smoked less than 11
      cigarettes a day, while the FSH levels were significantly lower. CONCLUSIONS: In
      clinical practice, single reference intervals can be used for men aged 20 - 69
      years for T and E2 measured with the Elecsys method, but separate age-dependent
      reference intervals should be used for FTc, LH, FSH, and SHBG. In addition,
      distinct reference intervals for T should be established for non-smokers or
      smokers (1 - 10 cigarettes/day) and smokers (> or = 11 cigarettes/day).

PMID- 22582503
TI  - Renin inhibitors inhibited the activity of recombinant human renin but not
      activity in healthy human plasma.
AB  - BACKGROUND: Activity of renin substrate cleavage (renin-like activity) was
      measured in vitro in plasma samples obtained from healthy human volunteers.
      METHODS: Renin-like activity was determined using FRET (Fluorescence Resonance
      Energy Transfer) human renin substrate. Recombinant human renin and human plasma
      showed dose-dependent cleavage activity of FRET human renin substrate. RESULTS:
      Activity of recombinant human renin was completely inhibited by either a
      peptidergic or a non-peptidergic renin inhibitor. However, renin-like activity in
      human plasma was not inhibited by these renin inhibitors. In a mixture of
      recombinant renin and human plasma, renin inhibitors inhibited only that part of
      the activity caused by recombinant renin, while the activity in plasma still
      remained. Human plasma did not show cleavage activity of rat FRET renin
      substrate. Native human prorenin showed cleavage activity of human renin
      substrate. This activety was also completely inhibited by renin inhibitors.
      Immunoprecipitation with anti-renin or anti-prorenin antibodies did not reduce
      the activity in human plasma. Renin-like activity in human plasma was abolished
      by degeneration of protein when sample was heated to 95 degrees C. Activity of
      both recombinant renin and human plasma was significantly inhibited by a protease
      inhibitor cocktail. CONCLUSIONS: These results suggest that the activity of renin
      substrate cleavage in human plasma is not mainly caused by the renin or prorenin
      molecule, but probably by other proteases.

PMID- 22582504
TI  - Functional state analysis of phagocytic cells of patients with type 2 diabetes
      and pulmonary tuberculosis.
AB  - BACKGROUND: The phagocytic function in pulmonary tuberculosis (PTB) and Type 2
      diabetes (T2D) has been explored mainly in macrophages but not in
      polymorphonuclears (PMN). The purpose of this study was to determine the
      functional status of PMN leukocytes in patients with pulmonary tuberculosis
      (PTB), Type 2 diabetes (T2D), and in patients with both diseases. METHODS: An
      observational, prospective, and comparative study was carried out. 30 ambulatory
      patients with T2D, 10 with PTB undergoing treatment and 10 patients with PTB and
      T2D, and 44 healthy subjects were studied. PMN leukocytes were separated, the
      capacity of these cells to produce hydrogen peroxide and to reduce nitroblue
      tetrazolium (NBT) in response to stimulus with the phorbolic ester of myristic
      acid (PMA) was measured; and the capacity of PMN leukocytes to adhere to surfaces
      was determined. RESULTS: Concerning the test for adherence, on comparing healthy
      subjects with patients with T2D+PTB, we observed a clear decrease in cellular
      adherence in the group of patients with both diseases; it was statistically
      significant (p = 0.007).With regard to phagocytic function, we observed that in
      NBT reduction as well as in hydrogen peroxide production, statistically
      significant differences were not obtained on comparing healthy subjects with any
      of the three groups of patients. CONCLUSIONS: We observed a clear decrease in
      cellular adherence when both diseases co-exist. These results could indicate the
      need for the co-existence of T2D and TB to cause deterioration in the cells'
      adherence activity. The microtechniques employed permit the evaluation in a
      practical manner of certain phagocytic-activity expressions.

PMID- 22582505
TI  - Quantity and quality assessment of DNA extracted from saliva and blood.
AB  - BACKGROUND: Saliva has been suggested as an attractive resource for evaluating
      physiological and pathological conditions in humans. This study aims to evaluate
      saliva sampling as an alternative to blood sampling for molecular testing.
      METHODS: We compared the yield, purity, and performance of DNA isolated from
      blood to that isolated from saliva using the non-invasive collection kit (Oragene
      DNA OG500 and OG575 kit). Saliva DNA was extracted by manual purification and
      QIAamp DNA mini kit. Blood DNA was isolated by salt-precipitation and DNAzol
      reagent. We also evaluated the quality of saliva DNA by PCR-based analysis.
      RESULTS: We found that the DNA yield from saliva (7.8 microg/0.5 mL saliva
      sample) from the manual purification method was comparable to the DNA yield from
      blood by the salt precipitation method (7.4 ug/0.5 mL blood sample). DNA
      extracted from saliva and blood were both of high purity (A260/280 > 1.70).
      Genotype results (PCR-RFLP and direct sequencing) for all sets of blood-saliva
      DNA samples were in 100% concordance. CONCLUSIONS: Saliva samples, when extracted
      by the manual purification method, provide a similar amount of human DNA as
      compared to the amount obtained from blood. Saliva is a viable alternative DNA
      source for genotyping studies.

PMID- 22582506
TI  - Matrix metalloproteinase-9 silencing by RNA interference promotes the adhesive
      invasive switch in HT1080 human fibrosarcoma cells.
AB  - BACKGROUND: A high level of matrix metalloproteinase-9 (MMP-9) is associated with
      human tumor invasion and/or metastasis. The HT1080 human fibrosarcoma cell line
      is highly invasive and metastatic which constitutively express MMP-9. METHODS:
      HT1080 cells transfected with a double stranded RNA that targeted the MMP-9 mRNA
      and the cellular characteristics were examined before and after interference. The
      inhibition effects of MMP-9 interference on the tumor growth of HT1080 cells in
      nude mice was also tested by xenograft assay. RESULTS: MMP-9 extinction in HT1080
      resulted in the following: (1) inhibited cell mobility; (2) increased cell
      adhesion, and (3) attenuated tumor cell migration. In addition, MMP-9 knockdown
      concomitantly resulted in decreased levels of soluble ICAM-1, leading to an
      adhesion defect and tumor metastasis. Moreover, in vivo assay further
      demonstrated MMP-9 interference affecting the tumorigenesis of HT1080 cells in
      mice as follows (1) inhibition of tumor growth; (2) reduced tumor volume, and (3)
      prolonged survival time. CONCLUSIONS: Our observations defined a novel critical
      role for MMP-9 in the progression of HT1080 fibrosarcoma by changing the inter
      cellular adhesion molecular-1 from membrane-anchored state to a soluble one which
      provides a target for promising tumor therapy in clinics.

PMID- 22582507
TI  - Improvement of pustulosis palmaris et plantaris by periodontal infection control
      in a patient with chronic periodontitis.
AB  - BACKGROUND: Pustulosis palmaris et plantaris (PPP) is a chronic, inflammatory,
      autoimmune-type disease characterized by sterile pustules of skin. The skin
      inflammation is influenced by several factors such as drugs, sunlight, metabolic
      and psychogenic factors as well as metal allergy. Here, we report a rare case
      that intensive periodontal treatment might have contributed to the improvement of
      skin inflammation. RESULTS: Skin inflammation regressed 1 month after intensive
      periodontal treatment. Both CD4/CD8 ratio and % of B cells in the blood sample
      were slightly decreased corresponding to the improvement of periodontal
      inflammation. CONCLUSIONS: Infection control of periodontal lesions might be one
      of attractive therapeutic targets in management of PPP.

PMID- 22582508
TI  - Analysis of a multiple nuclear dots pattern in a large cohort of dermatological
      patients.
AB  - BACKGROUND: Anti-multiple nuclear dots (MND) antibodies are the markers of
      primary biliary cirrhosis (PBC), but can also be found in patients with other
      autoimmune diseases. METHODS: We looked for MND in 9189 sera belonging to 6240
      patients stored for autoimmune diseases with prevalent cutaneous features.
      RESULTS: Fifty sera proved anti-MND-positive and came from 15 different patients:
      6 had lupus erythematosus, 2 dermatomyositis, 2 lichen planus, 1 stroke, 1
      telogen effluvium, 1 autoimmune thrombocytopenia, and 2 undifferentiated
      connective tissue disease. CONCLUSIONS: Anti-MND antibodies can be found not only
      in patients with PBC, but in connective tissue diseases as well. They can be
      associated with other fluoroscopic patterns and their titers can vary over the
      years, never correlating with the disease activity or with particular cutaneous
      features. Although anti-MND antibodies found are directed to the Sp100 antigen of
      the nuclear dots, it remains unclear whether their molecular target is the same
      amino-acid domain as in PBC.

PMID- 22582509
TI  - Influence of hemolysis on routine laboratory cardiac marker testing.
AB  - BACKGROUND: Reliable information on the potential bias arising from processing in
      vitro hemolysis specimens referred for conventional cardiac biomarker testing is
      scarce and controversial as yet. The present investigation was designed to assess
      the influence of low levels of in vitro hemolysis on cardiac biomarker testing.
      METHODS: Three aliquots, prepared by serial dilutions of homologous hemolysed
      samples collected from 14 different subjects and containing final concentrations
      of plasma hemoglobin of 0, 0.3, and 0.6 g/L were tested for the following
      parameters: cardiac troponin I (cTnI) and T (cTnT), myoglobin (Myo), creatine
      kinase isoenzyme-MB (CK-MB), brain natriuretic peptide (BNP) and NT-prohormone
      brain natriuretic peptide (NT-pro BNP). RESULTS: No statistically significant
      differences were observed in any of the parameters tested nor did the bias
      achieve clinical significance. CONCLUSIONS: The results of this study show that
      moderate hemolysis, as low as 0.6 g/L, has no influence on the reliability of
      cardiac biomarker testing.

PMID- 22582510
TI  - Soluble CD40L release as test for functional platelet loss.
AB  - BACKGROUND: During platelet storage, alterations of the platelet function,
      'platelet storage lesion', can be observed resulting in a reduced platelet
      viability. The release of soluble CD40 ligand (sCD40L) by platelets reflects
      different aspects of platelet metabolism and activity. Therefore, we used the
      sCD40L release to test for functional platelet loss in platelet products during
      storage in comparison to the formation of thromboxane (TXB2). METHODS: On day 1,
      3, and 5 in single donor apheresis platelet products (n = 8) under routine
      storage conditions, sCD40L (measured by ELISA) and TXB2 (measured by RIA) were
      determined after platelet stimulation (recalcification and clot formation).
      Results were related to a therapeutic unit (TU = 2 x 10*11 platelets). RESULTS:
      In platelet-rich plasma of the donors, sCD40L release was 42.5 +/- 7.1 ng/TU and
      TXB2 formation 2,183 +/- 576 ng/TU. On day 1, 3, and 5 sCD40L release was reduced
      to 95%, 64%, and 57% and TXB2 formation to 92%, 80%, and 65% of the respective
      control values. CONCLUSIONS: In single donor apheresis PCs, sCD40L release and
      TXB2 formation showed a comparable course over storage time and were reduced to
      about 60% of the respective control values after a storage period of 5 days.
      These findings are in line with literature data indicating that a functional
      platelet loss of about 30% will occur after 5 days of storage. Overall, sCD40L
      release could be easily induced by recalcification and clot formation and can be
      used as a marker for functional platelet loss.

PMID- 22582511
TI  - Proficiency of PCR in hospital settings for nonculture diagnosis of invasive
      meningococcal infections.
AB  - BACKGROUND: Meningococcal meningitis requires rapid diagnosis and immediate
      management which is enhanced by the use of PCR for the ascertainment of these
      infections. However, its use is still restricted to reference laboratories.
      METHODS: We conducted an inter-laboratory study to assess the implementation and
      the performance of PCR in ten French hospital settings in 2010. RESULTS: Our data
      are in favour of this implementation. Although good performance was obtained in
      identifying Neisseria meningitidis positive samples, the main issue was reported
      in identifying other species (Streptococcus pneumoniae and Haemophilus
      influenzae) which are also involved in bacterial meningitis cases. CONCLUSIONS:
      Several recommendations are required and, mainly, PCR should target the major
      etiological agents (N. meningitidis, S. pneumonia, and H. influenzae) of acute
      bacterial meningitis. Moreover, PCR should predict the most frequent serogroups
      of Neisseria meningitidis according to local epidemiology.

PMID- 22582512
TI  - Hba(1c) as a tool for the diagnosis of type 2 diabetes: comparison with fasting
      glucose.
AB  - BACKGROUND: Glycated hemoglobin (HbA(1c)) has been proposed for the diagnosis of
      diabetes. However, several countries have not incorporated its use for this
      purpose yet and there is no consensus on a suitable cut-off point of HbA(1c) for
      the diagnosis of diabetes. Thus, the aim of this study was to evaluate the
      diagnostic characteristics of HbA(1c) and fasting plasma glucose (FPG) for the
      assessment of type 2 diabetes. METHODS: FPG, HbA(1c), and creatinine levels were
      assessed in 47 patients with type 2 diabetes and 46 healthy controls. RESULTS:
      The areas under the curve for HbA(1c) > or = 6.5% and FPG > or = 7.0 mmol/L were
      0.97 and 0.92, respectively. HbA(1c). has a slightly higher ability to
      discriminate type 2 diabetes compared with FPG. The association between HbA(1c)
      and type 2 diabetes was independent of gender, age, hypertension, smoking, and
      body mass index. CONCLUSIONS: HbA(1c) was able to be used for the diagnosis of
      type 2 diabetes.

PMID- 22582513
TI  - Interference studies: focus on blood cell lysates preparation and testing.
AB  - BACKGROUND: Hemolyzed specimens are the most frequent preanalytical problem and a
      serious challenge for clinical laboratories, inasmuch as the presence of
      intracellular components, cellular debris, and stroma in the test sample might
      influence the reliability of clinical chemistry, coagulation, and immunochemistry
      testing. The identification of reliable limits for establishing whether a certain
      degree of hemolysis in the specimen would produce a clinically significant bias
      in the test system is thereby crucial. METHODS: The aim of this article is to
      provide an overview of the current scientific literature about the available
      methods to lysate blood cells and their use in interference studies. RESULTS:
      Several approaches have been proposed for producing the hemolysate (e.g.,
      freezing and thawing the sample, lysis of whole blood by distilled water with or
      without detergents, sonication, passing the blood through a fine collection
      needle, stirring the blood with a metallic bar or applying the blade of a tissue
      homogenizer to the sample), and testing its interference. CONCLUSIONS: A major
      standardization in the approaches for generating the hemolysate is needed in
      order to increase the comparability across interference studies and provide the
      laboratory community with transferable and thereby "usable" information. The
      methods able to produce a lysis of leukocytes and platelets other than
      erythrocytes should however be preferred, since they more reliably mirror the
      spurious hemolysis that is typically found in the specimens received in clinical
      laboratories.

PMID- 22582514
TI  - Combination of copeptin and highly sensitive troponin I for diagnosing acute
      myocardial infarction at emergency department admission.

PMID- 22582515
TI  - [Customer patient].

PMID- 22582516
TI  - [Postoperative care after cataract surgery].
AB  - The postoperative treatment of cataract surgery is an important element for
      success of the surgery. The postoperative therapy primarily aims at the
      prevention of intraocular bacterial infection by administration of antibiotics.
      Anti-inflammatory drugs can suppress the operation-related inflammation. In
      addition to fundamental risks of topical eye drop application, this review
      article discusses the current therapeutic strategies for the prevention of
      postoperative bacterial infection and suppression of surgically induced
      inflammation.

PMID- 22582517
TI  - [Outpatient and inpatient medication - interface problems for patients].

PMID- 22582518
TI  - [Medication safety in hospitals].
AB  - Drug therapy is one of the most common therapeutic interventions in the medical
      care of in-patients. It is a complex risk-associated procedure, which is why risk
      prevention is of top priority in medication safety. Medical care in hospitals is
      organised via various forms of distribution, e.g. the traditional distribution on
      the ward or as computerised unit dose drug dispensing system. In order to improve
      medication safety, the computerised unit dose drug dispensing system was
      introduced in the Ruppiner Kliniken in 2009. The implementation of the system to
      the clinic was scientifically evaluated within the scope of a diploma thesis
      which focused on the examination and analysis of medication safety and its
      evolvement. Amongst others, medication errors were detected and classified (via
      DokuPIK). The thesis showed that the implementation of the computerised unit dose
      system had a positive impact on the reduction of consequences of common and
      clinically relevant medication errors, thereby enhancing medication safety for
      the patient.

PMID- 22582519
TI  - [What are the are the adverse health effects of sweeteners?].

PMID- 22582520
TI  - Exercise explained. What to know to get the most benefit from working out.

PMID- 22582521
TI  - Relieving the pressure. The basics of blood pressure control.

PMID- 22582522
TI  - Ready for anything. How to be prepared in case of severe highs or lows.

PMID- 22582523
TI  - Licensed to thrive. The ADA's view: driving laws should treat people with
      diabetes as individuals.

PMID- 22582524
TI  - Rodeo hero. Boyd Bush tackles his biggest challenge--and that's no bull.

PMID- 22582525
TI  - Plan of action. Customizing your diabetes management puts you in control.

PMID- 22582526
TI  - Test with success. 10 ways to master your meter.

PMID- 22582527
TI  - New hope for ending complications. Working together to protect your body from
      diabetes damage.

PMID- 22582528
TI  - Viva fajitas!

PMID- 22582529
TI  - Herbal melody.

PMID- 22582530
TI  - Driven design. Process improvement tools guide replacement project.

PMID- 22582531
TI  - Elder care. Designs to support aging acute care patients.

PMID- 22582532
TI  - Ready to deliver? Assessing an organization's ability to take on projects.

PMID- 22582533
TI  - Handy solutions. Hygiene compliance monitoring goes high-tech.

PMID- 22582534
TI  - PDC summit shows value of teamwork.

PMID- 22582535
TI  - Developing excellent customer service.

PMID- 22582536
TI  - Steamed up. Revised ANSI/AAMI sterilization standard in practice.

PMID- 22582537
TI  - Utilizing competency-based tools for infection prevention.

PMID- 22582538
TI  - Surface safety. Best practices in surface and medical device disinfection.

PMID- 22582539
TI  - Staying relevant.

PMID- 22582540
TI  - Screening for lung cancer in Malaysia: are we there yet?

PMID- 22582541
TI  - Beta-blockers for heart failure: an evidence based review answering practical
      therapeutic questions.
AB  - Beta-blockers are underutilised in heart failure because clinicians may be unsure
      whether all beta-blockers are useful, how therapy should be initiated and whether
      beta-blockers are contraindicated in some patients. Bisoprolol, carvedilol and
      metoprolol succinate have been clearly proven to reduce mortality and
      hospitalisation in patients with Class II to IV heart failure; limited evidence
      also support short-acting metoprolol tartrate and nebivolol. Initiating dose
      should be very low (1.25 mg bisoprolol, 3.125 mg carvedilol, 12.5 mg metoprolol
      succinate) and increased gradually over weeks. Treatment benefit appears
      proportional to magnitude of heart rate reduction and thus target dose should be
      the maximum tolerated for adequate bradycardia. Even in decompensated heart
      failure or those with coexisting bronchospasm, beta-blockers are not
      contraindicated although the dose may have to be reduced or withheld temporarily.
      The consistent trial data should reassure clinicians and encourage them to
      confidently initiate beta blockers in patients with systolic heart failure.

PMID- 22582542
TI  - Risk factors for typhoid outbreak in Sungai Congkak Recreational Park, Selangor
      2009.
AB  - Typhoid fever continues to pose public health problems in Selangor where cases
      are found sporadically with occasional outbreaks reported. In February 2009,
      Hospital Tengku Ampuan Rahimah (HTAR) reported a cluster of typhoid fever among
      four children in the pediatric ward. We investigated the source of the outbreak,
      risk factors for the infection to propose control measures. We conducted a case
      control study to identify the risk factors for the outbreak. A case was defined
      as a person with S. typhi isolated from blood, urine or stool and had visited
      Sungai Congkak recreational park on 27th January 2010. Controls were healthy
      household members of cases who have similar exposure but no isolation of S. typhi
      in blood, urine or stool. Cases were identified from routine surveillance system,
      medical record searching from the nearest clinic and contact tracing other than
      family members including food handlers and construction workers in the
      recreational park. Immediate control measures were initiated and followed up.
      Twelve (12) cases were identified from routine surveillance with 75 household
      controls. The Case-control study showed cases were 17 times more likely to be 12
      years or younger (95% CI: 2.10, 137.86) and 13 times more likely to have ingested
      river water accidentally during swimming (95% CI: 3.07, 58.71). River water was
      found contaminated with sewage disposal from two public toilets which effluent
      grew salmonella spp. The typhoid outbreak in Sungai Congkak recreational park
      resulted from contaminated river water due to poor sanitation. Children who
      accidentally ingested river water were highly susceptible. Immediate closure and
      upgrading of public toilet has stopped the outbreak.

PMID- 22582543
TI  - Review of ear, nose and throat foreign bodies in Sarawak General Hospital. A five
      year experience.
AB  - OBJECTIVE: Ear, nose and throat foreign bodies are common in ENT clinical
      practice. This study was designed to establish the local data of
      otorhinolaryngeal foreign bodies in term of prevalence among paediatric and adult
      groups, the clinical features, types of foreign body at different sites, and
      laterality of foreign bodies. METHOD: This study was carried out at ENT
      department, Sarawak General Hospital, Malaysia, from 1st January 2005 to 31st
      December 2009. A total of 1084 cases were included and statistically analyzed.
      RESULT: Ear foreign bodies showed the highest incidence which was consisted of
      480 (44.3%) cases, followed by nose in 270 (24.9%) cases, pharynx in 251 (23.2%)
      cases, esophagus in 57 (5.3%) cases and laryngo-tracheobronchial tree in 26
      (2.4%) cases. Otorhinolaryngeal foreign bodies occurred more frequently in 0-10
      year old age group which constituted 651 (60.1%) cases. The descending order of
      frequency for foreign body sites in adult was pharynx (17.2%), ear (12.8%),
      esophagus (3.1%), nose (1.7%) and laryngo-tracheobronchial tree (1.1%). The type
      of foreign bodies varies with age group and site of foreign body lodgement. In
      general, common foreign bodies in both adult and children were food related, with
      the additional of small objects such as plastic toy in paediatric group.
      CONCLUSION: Otorhinolaryngeal foreign bodies were found more frequently in
      children. The types of foreign body were different from age group and sites of
      foreign body lodgement. The local food constituted the highest incidence of ear,
      nose, and throat foreign bodies with additional of plastic toys in paediatric
      group.

PMID- 22582544
TI  - Glycaemic control and cost analysis when changing from gliclazide co-administered
      with metformin to pre-combined glibenclamide-metformin tablets in type 2 diabetes
      mellitus.
AB  - Type-2 diabetes mellitus (T2DM) patients who were on gliclazide co-administered
      with metformin were changed to pre-combined glibenclamide-metformin tablets in
      the Endocrine Clinic, Penang Hospital. We conducted a retrospective study to
      evaluate the differences in glycaemic control and treatment cost following the
      change. Eighty patients (60% females) with a mean age of 55 years old were
      studied. Mean glycosylated haemoglobin (HbAlc) reduction was -0.92% (p<0.01) and 
      0.83% (p<0.01) after three and six months respectively. Patients with baseline
      HbA1c > or =8% had greater reduction in mean HbA1c (-1.36%) after six months. The
      treatment cost per month was reduced by 45% at 3 months (p<0.01)) and 44% at 6
      months (p<0.01). The change to pre-combined glibenclamide-metformin tablets
      resulted in significant improvement in glycaemia and reduction in treatment cost

PMID- 22582545
TI  - Preliminary study on association of beta2-adrenergic receptor polymorphism with
      hypertension in hypertensive subjects attending Balok Health Centre, Kuantan.
AB  - Polymorphisms within the beta2-adrenergic receptor (ADRB2) gene have been
      repeatedly linked to hypertension. Among the ADRB2 polymorphisms detected,
      Arg16Gly and Gln27Glu codons are considered the two most important variations.
      The amino acid substitution at these codons may lead to abnormal regulation of
      ADRB2 activity. The aim of the present study was to assess the association
      between ADRB2 polymorphisms and hypertension. This case-control study consisted
      of 100 unrelated subjects (50 hypertensive and 50 matched normal controls).
      Arg16Gly and the Gln27Glu polymorphisms were analyzed by polymerase chain
      reaction-restriction fragment length polymorphism assay. There were no
      significant evidence of association in allelic and genotypes distribution of
      Arg16Gly and Glu27Gln with blood pressure and hypertension. These findings
      suggest that the variation within codon 16 and 27 of ADRB2 gene were unlikely to
      confer genetic susceptibility for hypertension in our population samples.

PMID- 22582546
TI  - Geographical variation of cardiovascular risk factors in Malaysia.
AB  - The purpose of this study was to describe differences in cardiovascular risk
      factor prevalences and clustering patterns among the states and federal
      territories of Malaysia. Risk factors considered were abdominal obesity,
      diabetes, hypertension, hypercholesterolemia and smoking. Using data from the
      third National Health and Morbidity Survey (NMHS III) in 2006, we estimated the
      states and federal territories risk factor prevalences and clustering patterns to
      map the cardiovascular burden distribution in Malaysia. There was a clear
      geographical variation in the distribution of the individual risk factors as well
      as in its clustering with remarkable impact seen in Peninsular Malaysia. Perlis,
      Kedah and Kelantan were the most affected states overall.

PMID- 22582547
TI  - The association between dyslipidaemia and types of antipsychotic medications
      among patients with chronic schizophrenia.
AB  - This cross sectional study aimed to explore the association between dyslipidaemia
      and types of antipsychotics in 100 patients with chronic schizophrenia. Lipid
      profile, weight, height and waist circumference together with other relevant
      factors were measured. We found there was a high rate of dyslipidaemia among
      patients with chronic schizophrenia treated with antipsychotics (66%), however
      there was no significant difference found between typical or atypical
      antipsychotics (OR=1). All sociodemographic and clinical factors were not
      significantly associated with dyslipidaemia. Only non-Malays were found to have
      significant dyslipidaemia (p<0.1). Effective management is needed to deal with
      the dyslipidaemia in this group.

PMID- 22582548
TI  - Cholangiocarcinoma: a 10-year experience of a single tertiary centre in the multi
      ethnicity-Malaysia.
AB  - Cholangiocarcinoma (CCA) is a rare biliary tract epithelial malignancy. We
      described the clinical features of CCA patients in our institution. A 10-year
      retrospective study of patients with cholangiocarcinoma in University Malaya
      Medical Centre was conducted. Clinical data and outcomes in relation to the three
      anatomical groups of CCA were collected and analysed. Of the 69 patients that
      were included 55% were male. Mean age was 61 years. Twelve (17%) had
      intrahepatic, 38 (55%) perihilar and 19 (28%) distal tumour. Mean age (p=0.043),
      median duration of symptoms (p=0.011), jaundice (p<0.001), total bilirubin level
      (p=0.003), INR (p=0.005) and mean tumour size (p=0.048) were significantly
      related to the site of tumour. Only 12 patients had curative resection with seven
      R0 resections. Cholangiocarcinoma is increasingly diagnosed in our population.
      Despite that, the diagnosis is still often late. Age, jaundice and tumour size
      may predict anatomical location of CCA.

PMID- 22582549
TI  - Publication productivity and citation analysis of the Medical Journal of
      Malaysia: 2004 - 2008.
AB  - We analysed 580 articles (original articles only) published in Medical Journal of
      Malaysia between 2004 and 2008, the resources referenced by the articles and the
      citations and impact received. Our aim was to examine article and author
      productivity, the age of references used and impact of the journal. Publication
      data was obtained from MyAIS database and Google Scholar provided the citation
      data. From the 580 articles analyzed, contributors mainly come from the
      hospitals, universities and clinics. Contributions from foreign authors are low.
      The useful lives of references cited were between 3 to 11 years. ISI derived
      Impact factor for MJM ranged between 0.378 to 0.616. Journal self-citation is
      low. Out of the 580 sampled articles, 76.8% have been cited at least once over
      the 5 years and the ratio of total publications to citations is 1: 2.6.

PMID- 22582550
TI  - Acral melanoma of the extremities: a study of 33 cases Sarawakian patients.
AB  - BACKGROUND: Acral melanoma involve the non-pigmented palmoplantar and subungual
      areas and are commonly seen among Asians. Patients commonly display advanced
      stage of disease at presentation. It may appear unnoticed and mimic benign
      lesions. METHODS: Data for this retrospective study was retrieved from
      Histopathology Unit, Sarawak General Hospital, Malaysia archive from 2003 to
      2009. RESULT: 62.3% cases of malignant melanoma were acral melanoma. The mean age
      of diagnosis was 64.3 +/- 12.1. The involved sites were the heel (39.4%), middle
      and frontal plantar area (24.2%), toe (24.2%) and web spaces (9.1%). The clinical
      presentations were; an enlarging mass (60.6%), non-healing ulcer (24.2%) and
      abnormal pigmented lesion (15.2%). Most cases exhibited Breslow thickness >4.00
      mm (87.9%) and Clark's levels V (50%). The majority showed moderate (non brisk)
      tumour infiltrating lymphocytes (57.6%). Ulceration (84.8%) and lymphovascular
      involvement were seen (24.2%). CONCLUSION: Acral melanoma is the commonest
      malignant melanoma in this Sarawakian cohort. Most of the cases presented with
      advanced stage disease.

PMID- 22582551
TI  - A retrospective review on successful management of Penicillium marneffei
      infections in patients with advanced HIV in Hospital Sungai Buloh.
AB  - Penicillium marneffei is a dimorphic fungus which commonly causes a life
      threatening systemic fungal infection in an immunocompromised host. It has been
      recognized as an AIDS defining illness in Malaysia since the beginning of the HIV
      pandemic. The presence of various non specific clinical presentations, especially
      the characteristic umbilicated papular rashes with central necrosis which lead to
      significant ill health in immunocompromised patients should alarm clinicians to
      the possibility of Penicillium marneffei infection and prompt investigations
      accordingly. Simple investigations like blood culture and fungal staining of the
      skin scrapping can confirm the diagnosis in the majority of cases. Early
      treatment with appropriate systemic antifungal for a definite duration will
      significantly decrease the mortality rate from penicilliosis.

PMID- 22582552
TI  - Reproductive function after treatment of ovarian germ cell malignancy.
AB  - OBJECTIVE: This study was undertaken to evaluate the reproductive and oncologic
      outcomes of patients diagnosed with Ovarian Germ Cell Malignancy (OGCM) who
      underwent fertility preserving surgery and adjuvant chemotherapy treated in
      Gynaecology Oncology Unit, Sultanah Bahiyah Hospital, Kedah, Malaysia. METHODS:
      We retrospectively reviewed 33 patients who had fertility preserving surgery and
      adjuvant chemotherapy in our center from 2000 - 2010. Gynaecology oncology record
      and histopathology database were reviewed. Patients were contacted, assessed and
      interviewed via telephone using standardized questionnaire to assess their
      menstrual, reproductive function and disease status after treatment, post
      therapeutic status of pregnancy or delivery and overall survival. RESULT: Thirty
      three patients diagnosed with OGCM underwent unilateral salphingo oophorectomy
      and staging surgery followed by adjuvant chemotherapy (BEP regimen). The mean age
      at presentation was 19.8 years (range, 9 -34 years). Histological subtypes were
      21.2% dysgerminoma, 21.2% immature teratoma, 42.4% yolk sac tumour and 15.2%
      mixed germ cell tumour. After treatment, 71.4% resumed their menstrual cycles
      within 6 months. During follow up, 5 patients conceived with 5 live birth
      deliveries and 3 miscarriages (3 patients had two pregnancies). The overall
      survival rate was 87.9% with median follow up of 45.2 months. 30.3% of patient
      had disease recurrence with median disease free interval of 5 months while 6.0%
      had disease progression despite of adjuvant chemotherapy. One of the most
      important adverse prognostic factors for recurrence and disease progression is
      Yolk sac tumour (non DSG/IMT) histotype. CONCLUSION: Fertility preserving surgery
      and adjuvant chemotherapy appear to have little effect on fertility and menstrual
      cycle with a good overall survival. Patients diagnosed with histopathological
      yolk sac tumour element had poor outcome and perhaps need more aggressive and
      longer adjuvant therapy.

PMID- 22582553
TI  - Qualitative flow cytometric analysis of Malaysian myelodysplastic syndromes (MDS)
      patients.
AB  - Myelodysplastic syndromes (MDS) are a group of haematological malignancies
      categorized by ineffective hematopoiesis that result in dysplasia. Although
      morphological diagnosis is a traditional and standard technique that is used for
      the diagnosis of MDS, the heterogeneous blood and bone marrow characteristics of
      MDS patients can potentially obscure the right diagnosis. Thus, we have utilized
      flow cytometric immunophenotyping as a supportive mechanism to obtain a more
      accurate and faster method for detection of abnormal markers in MDS. Flow
      cytometry was used for analyzing bone marrow samples from newly diagnosed MDS
      patients to investigate the abnormal antigen expression patterns in granulocytic,
      monocytic, erythroid, lymphoid lineages and myeloid precursors. The results were
      compared with those obtained from cases that had Idiopathic Thrombocytopenic
      Purpura (ITP) as a control. The most common abnormality found in the granulocytic
      lineage was the decrease of CD10. Low expressions of CD13 were the most frequent
      abnormality in the monocytic lineage. The erythroid lineage was found to have low
      expression of CD235A+/CD71+, reduce of CD71 and decreased CD235a. In conclusion,
      this method is useful for confirming cases in which it is difficult to make a
      diagnosis by morphology.

PMID- 22582554
TI  - Hearing loss and contributing factors among airport workers in Malaysia.
AB  - Sensorineural hearing loss is a common and important source of disability among
      the workers and often caused by occupational noise exposure. Aims of the study
      were to determine the prevalence and contributing factors of hearing loss among
      airport workers. A cross-sectional study was carried out at an airport in
      Malaysia. This study used stratified sampling method that involved 358 workers
      who were working in 3 different units between November 2008 and March 2009. Data
      for this study were collected by using questionnaires eliciting sociodemographic,
      occupational exposure history (previous and present), life-style including
      smoking habits and health-related data. Otoscopic and pure-tone audiometric tests
      were conducted for hearing assessment. Noise exposure status was categorize by
      using a noise logging dosimeter to obtain 8-hour Time-Weighted Average (TWA).
      Data was analyzed by using SPSS version 12.0.1 and EpiInfo 6.04. The prevalence
      of hearing loss was 33.5%. Age >40 years old (aOR 4.3, 95%CI 2.2-8.3) is the main
      risk factors for hearing loss followed by duration of noise exposure >5 years
      (aOR 2.5, 95%CI 1.4-4.7), smoking (aOR 2.1, 95%CI 1.2-3.4), duration of service
      >5 years (aOR 2.1, 95%CI 1.1-3.9), exposure to explosion (aOR 6.1, 95%CI 1.3
      29.8), exposure to vibration (aOR 2.2, 95%CI 1.1-4.3) and working in engineering
      unit (aOR 5.9, 95%CI 1.1-30.9). The prevalence rate ratio of hearing loss for
      nonsmokers aged 40 years old and younger, smokers aged 40 years old and younger,
      non-smokers older than 40 years old and smokers older than 40 years old was 1.0,
      1.7, 2.8 and 4.6 respectively. This result contributes towards better
      understanding of risk factors for hearing loss, which is relatively common among
      Malaysian workers.

PMID- 22582555
TI  - Perinatal postmortem: factors influencing uptake and subsequent outcomes in an
      Asian population.
AB  - AIM: To assess uptake of perinatal postmortems (PM) among mothers experiencing
      perinatal deaths. Subjective assessment of factors influencing uptake was
      studied. Analysis of perinatal PM outcomes and its impact on cause analyses of
      intrauterine fetal demise was made. METHOD: 2-year prospective audit on all
      mothers who had experienced stillbirths at a tertiary centre. Couples returning
      for their postnatal consultation following their stillbirths were offered a
      subjective questionnaire on issues pertaining to the request of PM and their
      decisions on the requests. Outcome of their PMs was collated. RESULT: 71 of 87
      (81.6%) women with stillbirths in the 2008-2009 (24 months) period were offered
      PM examination of their babies. The preliminary uptake of perinatal PM was 24
      (33.8%) at counseling and but only 12 (16.9%) finally had PMs performed.
      Perinatal PMs clinched a diagnosis in 5 of 12 cases (42%). Discrepancies existed
      between external examination by on-site obstetric doctors and subsequent
      examination by a perinatal pathologist. CONCLUSION: Perinatal PM is a valuable
      tool in the assessment of intrauterine fetal demise. Increasing the perinatal PM
      uptake may improve care of women with stillbirths. Factors affecting parental
      decisions are discussed.

PMID- 22582556
TI  - Level of knowledge, attitude and practice of night market food outlet operators
      in Kuala Lumpur regarding the usage of repeatedly heated cooking oil.
AB  - Consumption of repeatedly heated oil can be detrimental to health. The objective
      of this study was to determine the level of knowledge, attitude and practice of
      night market food outlet operators in Kuala Lumpur regarding the usage of
      repeatedly heated cooking oil. The quality of cooking oil was also investigated.
      A cross-sectional study involving pretested questionnaire was undertaken in April
      2009. The questionnaire was designed as a tool to collect data from the
      respondents (n=100) by face-to-face interview. The results showed that majority
      of respondents had only moderate (53.0%) or low (18.0%) level of knowledge
      regarding this issue. Most respondents (67.0%) agreed that it is not a good
      practice. The majority (69.0%) agreed that the usage of repeatedly heated cooking
      oil is detrimental to health. Despite that, most respondents (63.0%) admitted
      that they had used cooking oil repeatedly. Most (62.0%) of the cooking oil
      samples taken from the night market food outlets were considered fit for human
      consumption. In conclusion, the level of knowledge of night market food outlet
      operators in Kuala Lumpur regarding this issue needs to be improved in order to
      ensure the safety of fried food purchased from such establishments.

PMID- 22582557
TI  - Isolated optic neuritis secondary to presumed tuberculosis in an immunocompetent
      child.
AB  - Isolated optic neuritis as a presenting sign of tuberculosis in children is
      uncommon. We report a case of an immunocompetent child who displayed features of
      bilateral optic neuritis secondary to presumed tuberculosis. It is essential to
      highlight this alarming presentation in a child, as the presence of tuberculosis
      has re-emerged as a serious public health problem especially in developing
      countries.

PMID- 22582558
TI  - Dapsone syndrome--first Malaysian paediatric case report.
AB  - Dapsone syndrome is a potentially fatal hypersensitivity reaction to sulphone. We
      report a 12-year-old girl who developed high grade fever associated with intense
      jaundice, exfoliative skin rash and hepatomegaly after five weeks of starting the
      multidrug regimen for the treatment of Hansen's disease. Laboratory
      investigations revealed presence of leucocytosis with eosinophilia, deranged
      liver enzymes and an abnormal coagulation profile. Immediate cessation of the
      offending drug and administration of steroid proved successful. A high level of
      clinical awareness is fundamental for early diagnosis of dapsone syndrome as
      initiation of a prompt treatment may lead to rapid recovery.

PMID- 22582559
TI  - Coronary artery spasm (CAS) simulating inferior ST elevation myocardial
      infarction (STEMI).
AB  - Coronary arteries vasospasm (CAS) is commonly seen in invasive cardiology
      laboratory during diagnostic catheterization or coronary intervention. Though the
      incidence of Printzmetal angina is uncommon, coronary vasospasm resulting in
      acute myocardial infarct is rare, especially if there is no significant
      atherosclerotic plaque within the coronary vasculature.

PMID- 22582560
TI  - Ruptured abdominal aortic aneurysm treated by endovascular aneurysm repair under
      local anaesthesia.
AB  - A 68 year old man with significant cardiorespiratory risks factors presented with
      a ruptured thoracic aortic aneurysm (TAA). This was treated by emergency thoracic
      endovascular aneurysm repair (TEVAR) under general anaesthesia (GA). An
      incidental abdominal aortic aneurysm (AAA) was not treated. Eight months later,
      he presented with ruptured AAA. Due to the patient's compromised respiratory
      system, he underwent endovascular aneurysm repair (EVAR) under local anaesthesia
      (LA). He had a smoother post-operation recovery compared to the first repair
      under GA.

PMID- 22582561
TI  - Habitual non-traumatic cricothyroid joint dislocation: a rare case of rotated
      larynx.
AB  - A case of a 21 year old gentleman is described, with no history of preceding
      trauma, presenting with intermittent dysphagia to solids and fluids for 4 years.
      Neck examination at rest was normal. However on deep inspiration, the right
      thyroid lamina protrudes or becomes more prominent. The patient is able to return
      the larynx to its normal position with manual manipulation. Laryngeal examination
      with fibreoptic scope during rest and deep breath shows gross rotation of the
      laryngeal structures for more than 60 degrees on deep breath, with the vocal
      cords axis rotated to the left side. Management was conservative.

PMID- 22582562
TI  - An unusual presentation of latent autoimmune diabetes in adults.
AB  - Latent Autoimmune Diabetes in Adults (LADA) is an autoimmune form of type 1
      diabetes mellitus presenting in adulthood. It is often confused with other types
      of diabetes and therefore the management is frequently inadequate. Acute
      hyperglycemic crisis in the form of diabetic ketoacidosis (DKA) or hyperglycemic
      hyperosmolar state (HHS) are unusual findings. We report a clinical case of a 66
      year-old female who presented for the first time with DKA and was subsequently
      diagnosed as a case of LADA. Presumptive diagnosis of LADA was confirmed with the
      presence of autoantibody to glutamic acid decarboxylase 65 (Anti-GAD65 antibody).

PMID- 22582563
TI  - Gangrenous small bowel obstruction secondary to congenital internal herniation: a
      case report.
AB  - Congenital internal herniation is a rare condition presenting as recurrent
      abdominal pain or acute intestinal obstruction. In cases in which bowel
      incarceration or strangulation develop, rapid progression to bowel ischemia,
      necrosis or perforation is inevitable. Mortality in such cases has been reported
      to be as high as 50%. Despite advances in imaging modalities, arriving at a pre
      operative diagnosis of a congenital internal herniation remains a challenge. We
      report such a case where imaging was unsuccessful in determining the cause of
      intestinal obstruction in a 3 year old child. Congenital internal herniation may
      result in disastrous consequences if not addressed in a timely fashion due to its
      rarity. Hence a high index of clinical suspicion is needed to avoid missing this
      diagnosis in a child presenting with recurrent abdominal pain or acute intestinal
      obstruction.

PMID- 22582564
TI  - Polymodal therapy for high grade gliomas: a case report of favourable outcomes
      following intraoperative radiation therapy.
AB  - High grade gliomas, frequently with their infiltrative nature, often make the
      outcome from neurosurgical intervention alone unsatisfactory. It is recognized
      that adjuvant radiochemotherapy approaches offer an improved prognosis. For these
      reasons, we opted for surgical debulking, intraoperative radiation therapy (IORT)
      in combination with whole brain irradiation therapy and chemotherapy
      (temozolamide cycles) in the management of a 42 year-old lady with Glioblastoma
      Multiforme (GBM). Her troublesome symptoms improved after 3 months of this
      polymodal therapy and remained independently functional for more than two years.

PMID- 22582565
TI  - Longitudinal stent compression: a not so new percutaneous coronary angioplasty
      (PCI) complication.

PMID- 22582566
TI  - Use of newly available febuxostat in a case of chronic tophaceous gout
      contraindicated to allopurinol and probenecid.
AB  - Urate lowering therapy in this country has mainly been achieved by the use of
      allopurinol and probenecid. A new xanthine oxidase inhibitor called febuxostat
      has been approved in 2009 for treatment of hyperuricaemia in gout. In this
      report, we describe the management of a patient with chronic tophaceous gout
      using febuxostat. The reduction in serum uric acid to target levels was rapid,
      and the tophi size had also reduced significantly while on therapy. There was no
      unwanted side effect observed during the therapy. Therefore, febuxostat would be
      a useful alternative drug in the treatment of hyperuricaemia in gout patients who
      have contraindications to allopurinol and probenecid.

PMID- 22582567
TI  - Primary hepatic angiosarcoma: difficulty in clinical, radiological, and
      pathological diagnosis.
AB  - Hepatic angiosarcoma is a rare primary mesenchymal malignancy. Prognosis is poor
      and mortality occurs early. The diagnosis is challenging. Our case was an
      asymptomatic 70 year-old man referred, with incidental ultrasonography finding of
      multiple liver nodules. Diagnostic laparoscopic liver biopsy and the
      histopathological examination reported a haemangioma. Six months later, he became
      symptomatic and his health condition deteriorated rapidly.

PMID- 22582568
TI  - Perioperative very late stent thrombosis treated with thrombosuction.

PMID- 22582569
TI  - Infrasellar craniopharyngioma of the posterior nasal septum: a rare entity.
AB  - OBJECTIVE: To report an unusual location of infrasellar craniopharyngioma in a
      peadiatric patient. CASE REPORT: A six-year-old boy presented with persistent
      bilateral nasal obstruction for one year. Clinical examination revealed a
      posterior choanal mass arising from septum and the finding was confirmed by
      paranasal sinuses computed tomography scan. He then underwent wide local
      excision. Histopathological examination confirmed the diagnosis of
      craniopharyngioma (adamantinomatous type). There were no signs and symptoms of
      recurrence after a year of followup. CONCLUSION: Infracranial craniopharyngioma
      without sellar involvement is extremely rare. Persistent nasal obstruction
      without endocrine dysfunction is the common presentation. Radiological imaging is
      important to diagnose and assess the extent. The mainstay of treatment for
      infrasellar craniopharyngioma is surgery. Regular follow up is mandatory.

PMID- 22582570
TI  - Acute renal failure and posterior reversible encephalopathy syndrome following
      multiple wasp stings: a case report.
AB  - Wasp stings can present in various ways, ranging from mild self-limiting illness
      to severe multi organ failure with a potentially fatal outcome. We report a case
      of multiple wasp stings leading to acute renal failure needing prolonged dialysis
      support and posterior reversible encephalopathy syndrome.

PMID- 22582571
TI  - Takotsubo cardiomyopathy with meperidine.

PMID- 22582572
TI  - Concepts in the management of the overactive bladder in women.
AB  - The 'overactive bladder' is a common problem affecting the elderly female
      population especially after the menopause. Urgency with or without urge
      incontinence accompanied by frequency of micturition and nocturia are presenting
      symptoms. The diagnosis is established after excluding other diseases of the
      lower urinary tract which have similar presenting features. The aetiology is
      multifactorial and this problem often causes physical, psychological and
      emotional distress to the patient. Management can be provided by primary care
      physicians initiating behavioral changes which include life style interventions
      and bladder drills with or without antimuscarinic drugs. The recalcitrant patient
      not responding to conventional therapy should be referred for specialist care.
      Non-conventional treatment using acupressure, neuromodulation and surgical
      methods are only instituted in indicated cases.

PMID- 22582573
TI  - [Ideal direction for official Journal of Japan Surgical Society].

PMID- 22582575
TI  - [Overview of the cancer research].

PMID- 22582574
TI  - [New perspectives of Japan Surgical Society from the point of view of
      International Committee].

PMID- 22582576
TI  - [Intravital imaging of cancer cell dynamics].
AB  - Intravital imaging using two-photon laser scanning microscopy (TPSLM) can
      visualize the cellular dynamics in a living body. By recording spatiotemporal
      images, this technique allows the detection of unknown cell movements and related
      unknown phenomena in an environment in which blood circulation is maintained.
      Because of these advantages, this multidimensional in vivo analytical technique
      has attracted attention from various research fields. TPSLM has also been
      introduced in cancer research and utilized to visualize cancer cell movements. By
      determining cancer dynamics in vivo, it is expected that new cancer movement
      related molecules will be discovered, which could be novel therapeutic targets.
      This article introduces the TPSLM imaging technique and method of molecular
      analysis using this imaging system.

PMID- 22582577
TI  - [Development of minimal residual cancer cell research].
AB  - Micrometastases of cancer cells occur during the early stages of cancer or from
      minimal residual cancer cells with metastatic potential. Recent progress in
      measuring methods has enabled the detection of minimal residual cancer cells in
      areas such as circulating tumor cells (CTCs) in peripheral blood, disseminated
      tumor cells in bone marrow, and free tumor cells in lymph nodes and the
      peritoneal cavity. Recently, it has been reported that the phenotypes of CTCs are
      closely related to cancer stem cells, and thus they may be of interest as new
      biomarkers in cancer patients. The usefulness of CTCs as predictive markers for
      recurrence and prognosis was demonstrated in patients with breast and colorectal
      cancer. Progress in the early diagnosis of the therapeutic effects of
      chemotherapy combined with molecular targeted drugs has also been enhanced by the
      detection of CTCs. Furthermore, individualized, limited surgery based on sentinel
      node navigation surgery has been performed not only in patients with breast
      cancer but also in those with gastric cancer. The clinical significance of free
      tumor cells in the peritoneal cavity of colorectal cancer patients has also
      become an area of interest. These developments in minimal residual cancer cell
      research may lead to a new metastatic cascade concept and novel approaches to
      cancer therapy.

PMID- 22582579
TI  - [Application of epigenetics to cancer diagnosis and therapy].
AB  - Epigenetic modifications are responsible for the stable maintenance of cellular
      phenotypes and consist of DNA methylation and histone modifications. Epigenetic
      abnormalities can be causally involved in cancer development (driver) and can
      also be present as a passenger. Aberrant DNA methylation has unique
      characteristics different from point mutations and is utilized as a diagnostic
      target. First, aberrant DNA methylation can be present at a high level in
      noncancerous tissues, and because its level can correlate with cancer risk, it is
      useful as a cancer risk marker. Second, aberrant DNA methylation can be detected
      with high sensitivity and therefore it is used to detect cancer cells. Third, DNA
      methylation is stable at different time points, such as at biopsy and during
      chemotherapy, and provides a good source of biomarkers. In addition, resistance
      to contaminating cells makes DNA methylation useful in genome-wide screening of
      biomarkers for various clinicopathologic characteristics. From the therapeutic
      viewpoint, DNA demethylating agents have been approved for the treatment of
      myelodysplastic syndrome and histone deacetylase inhibitors for the treatment of
      cutaneous T-cell lymphoma. The next steps include increasing the specificity for
      target genes, the development of biomarkers for dose and response studies, and
      establishing a strategy to select drugs for combination therapy. The further use
      of epigenetics for diagnosis and therapy is warranted.

PMID- 22582578
TI  - [Current topics in mutations in the cancer genome].
AB  - Several oncogenes and tumor suppressor genes are involved in the multistep
      process of carcinogenesis in many cancer types. Recently, global mutational
      analyses have revealed that the cancer genome has far greater numbers of
      mutations than previously thought. Furthermore, the next-generation sequencing
      method, which has a different principle from conventional Sanger sequencing, has
      provided more information on the cancer genome such as new cancer-related genes
      and the existence of many rearrangements in solid cancers. Somatic mutations
      occurring in cancer cells are divided into "driver" and "passenger" mutations.
      Driver mutations confer a growth advantage upon the neoplastic clone and are
      crucial for carcinogenesis. The remaining large majority of mutations are
      passengers, which, by definition, do not confer a growth advantage. Driver genes
      with low-frequency mutation rates (less than 10%) are also involved in
      carcinogenesis along with well-known drivers with high-frequency mutations. There
      are now several celebrated examples of anticancer drugs of which the efficacy in
      cancer patients can be predicted based on the genotype of several driver genes,
      such as EGFR, KRAS, and BRAF on the EGFR signaling pathway. The complete catalogs
      of somatic mutations provided by the sequencing of the cancer genome are expected
      to prompt new approaches to diagnosis, therapy, and potentially prevention.

PMID- 22582580
TI  - [Role of microRNA in cancer development: biology and clinical applications].
AB  - The role of RNA, as commonly understood, is to carry the genetic code for protein
      from the DNA to the sites of protein production. Over the years, however, new
      forms of RNA were discovered, such as microRNA (miRNA) and large intergenic
      noncoding RNA, and the range of RNA function was extended, miRNA constitutes a
      large family of small, approximately 20-nucleotide-long, noncoding RNA which
      controls the expression of target genes at the posttranscriptional level. Recent
      studies have indicated that miRNA plays an essential role in cancer biology by
      affecting cell growth, differentiation, and apoptosis as well as the cell cycle.
      This review summarizes the newly determined role of miRNA in cancer development,
      discusses some controversies regarding different functions of miRNA, and
      highlights the prospects for clinical applications of miRNA, such as therapeutic
      targets and diagnostic markers.

PMID- 22582581
TI  - [The concept and significance of cancer stem cells].
AB  - Functional heterogeneity occurs in tumor withs a hierarchy in which tumor growth
      is driven by a small subset of cancer stem cells (CSCs). Like normal tissue stem
      cells, which are capable of self-renewal and multi-differentiation, CSCs have the
      ability to reconstitute tumors. CSCs also have the ability to resist
      chemoradiotherapy and give rise to cancer metastasis and recurrence. Therefore,
      eradication of CSCs will lead to complete cancer cure. In the process of
      developing CSC-targeted therapy, it is necessary to identify CSC-specific
      molecules, for which it is essential to identify definitive CSC markers and
      isolate CSCs with high accuracy. Although the targeting and regulation of CSCs
      have not yet been fully established, some reports showed that it is possible to
      target CSCs using molecules on which they are highly dependent or using
      differentiation induction similar to the normal tissue differentiation mechanism.
      It is expected that novel therapeutic molecules with high specificity and
      effectiveness will be found in the near future. In addition, the CSC concept has
      itself been evolving. It is necessary to clarify the exact nature of CSCs to
      establish a treatment strategy against them.

PMID- 22582582
TI  - [Significance of genome-wide association study in cancer].
AB  - The single-nucleotide polymorphism (SNP)-based genome-wide association study
      (GWAS) is now widely performed because of the development of new SNP genotyping
      technologies from 2007 onward. The GWAS provides a powerful approach to identify
      regions of the genome that harbor genetic variants conferring risk for disease
      without prior knowledge of location or function. During the past few years, the
      GWAS has identified numerous robust associations between specific chromosomal
      loci and different types of cancer. For nearly all regions identified in the
      GWAS, the per allele effect sizes estimated are < 1.5 and the mechanism of SNP in
      carcinogenesis was not clear. Consequently, GWAS findings underscore the complex
      nature of cancer. The combined effects may be sufficiently great to be useful for
      risk prediction, targeted screening, and prevention, particularly as more loci
      are identified. Some loci, such as 8q24, were identified as a cancer
      susceptibility region for many unrelated cancers, and therefore an investigation
      of those loci may disclose new mechanisms of carcinogenesis or unknown genes
      including noncoding RNA. Furthermore, the development of new strategies for GWAS
      analysis is expected.

PMID- 22582583
TI  - [Perioperative infection control in patients undergoing cardiovascular surgery].

PMID- 22582585
TI  - [Duodenum-preserving pancreatic head resection (DPPHR)].

PMID- 22582584
TI  - [What we can learn from a case of medical malpractice--a case of negligence
      denied on the premise that it is nearly impossible for a doctor on duty who is a
      non-specialist to diagnose at the level of a specialist].

PMID- 22582586
TI  - [Survey for Japanese surgeon's work environment and the response of hospital
      administrators to the increased income of medical service fee by surgeons--report
      from the Committee for the Improvements in Work Environment of Japanese
      Surgeons].

PMID- 22582587
TI  - [Operating room during natural disaster: lessons from the 2011 Tohoku
      earthquake].
AB  - OBJECTIVES: Objective of this study is to clarify damages in operating rooms
      after the 2011 Tohoku Earthquake. METHOD: To survey structural and non-structural
      damage in operating theaters, we sent questionnaires to 155 acute care hospitals
      in Tohoku area. RESULTS: Questionnaires were sent back from 105 hospitals
      (70.3%). Total of 280 patients were undergoing any kinds of operations during the
      earthquake and severe seismic tremor greater than JMA Seismic Intensity 6 hit 49
      hospitals. Operating room staffs experienced life-threatening tremor in 41
      hospitals. Blackout occurred but emergency electronic supply unit worked
      immediately in 81 out of 90 hospitals. However, emergency power plant did not
      work in 9 hospitals. During earthquake some materials fell from shelves in 44
      hospitals and medical instruments fell down in 14 hospitals. In 5 hospitals, they
      experienced collapse of operating room wall or ceiling causing inability to
      maintain sterile operative field. Damage in electric power and water supply plus
      damage in logistics made many operating rooms difficult to perform routine
      surgery for several days. CONCLUSIONS: The 2011 Tohoku earthquake affected
      medical supply in wide area of Tohoku district and induced dysfunction of
      operating room. Supply-chain management of medical goods should be reconsidered
      to prepare severe natural disaster.

PMID- 22582588
TI  - [Cooperation between the Department of Cardiovascular Surgery in University of
      Tsukuba and Cho-Ray Hospital, Ho-Chi-Minh City, Vietnam--for an attractive
      collaboration in international medical education].
AB  - The Department of Cardiac Surgery in Cho-Ray Hospital, Ho-Chi-Minh city stands
      for a representative high volume center in the south of Vietnam. In the
      department about 1,200 cases of open-heart surgery are performed in a year. In
      next era, they wish to improve their surgical quality, focusing on complex and
      low-weight congenital cases, mitral repair, maze operation and off-pump CABG.
      Since 2008, University of Tsukuba has started to collaborate with many
      departments in Cho-Ray Hospital as a project of international medical educations
      in Global 30, and has been establishing meaningful activities in the Department
      of Cardiac Surgery as well. We keep providing opportunities for education,
      research and training for young Vietnamese doctors and investigators as much as
      possible both in Cho-Ray Hospital and University of Tsukuba with some financial
      support. We believe that our steady collaboration with Cho-Ray Hospital will
      bring certain developments not only for Vietnamese but for ourselves.

PMID- 22582589
TI  - [Surgical skill training seminars for young doctors who belong to the multicenter
      -for the purpose of both regional cooperation and of eliminating the surgeon
      shortage].
AB  - Recently the shortage of surgeon is one of the serious problem in our country.
      And the chance to introduce young doctors the surgical world is decreasing
      because of new educational system for intern doctors has started. We plan the
      surgical skill improvement seminar for the intern doctors from various hospitals
      to introduce the surgical world widely with senior doctors from multicenter. The
      aim of this seminar is also to decrease the burden for the education of each
      institutions and to decrease the stress of the senior doctors for education.
      Moreover, this kind of seminar is quite useful from regional cooperation point of
      view, because gathering and doing the cooperation in the seminar makes the senior
      doctors become the familiar faces. The seminar was held twice since 2010.
      According to the questionnaire for both trainer and trainee, almost all trainee
      answered that this seminar is quite useful for the skill up of residents. And
      senior doctors answered that this seminar might contribute to the resolution of
      shortage of surgeons and to progress of the regional cooperation. This kind of
      seminar with senior doctors from multicenter may play an important role to
      improvement of shortage of surgeon and regional cooperation of each hospitals.

PMID- 22582590
TI  - [Retrospect of study on hypoxic physiology].

PMID- 22582591
TI  - [Synaptic vesicle recycling and Alzheimer's disease].
AB  - Loss of synapses correlates well with cognitive decline in Alzheimer's disease
      (AD). However, the molecular mechanisms underlying the synaptic dysfunction and
      loss are not well understood. Synaptic vesicle (SV) recycling is a key process
      for synaptic transmission. A body of evidences suggested that malfunction or loss
      of the machinery for SV recycling occurred in AD, which could result in
      disruption of neuronal circuitry. In this article, we summarized the recent
      progress in the research of synaptic proteins for SV recycling and the
      pathological changes of some proteins in AD.

PMID- 22582592
TI  - [Progress in study on organic anion transporters].
AB  - Organic anion transporters (OATs) belong to a family of poly-specific
      transporters mainly located in barrier epithelia such as renal proximal tubule,
      brain, liver and placenta. OATs interact with endogenous metabolic end products
      such as urate and acidic neutrotransmitter metabolites, as well as with a
      multitude of widely used drugs, including antibiotics, diuretics,
      antihypertensives and anti-inflammatory drugs. Thereby, OATs play an important
      role in renal drug elimination and have an impact on pharmacokinetics. This
      review summarizes current knowledge of the properties and functional roles of the
      cloned OAT family members detailed in tissue differences in expression and
      physiologic function, drug-drug interactions, and finally, gender-dependent
      regulation in health and diseased states.

PMID- 22582593
TI  - [Progress in prolactin receptor research].
AB  - Prolactin (PRL) is secreted by lactotrophs in the anterior pituitary and some
      extra-pituitary tissues such as breast, lacrimal gland, uterus, thymus and
      spleen, etc. Since PRL is closely related to growth hormone (GH) and placental
      lactogens (PL), it has been broadly accepted that PRL, GH and PL are resulted
      from the duplication of an ancestral gene. PRL regulates hundreds of biological
      functions by endocrine, paracrine and autocrine manners. Prolactin initiates its
      effects by binding to its receptor (PRLR). PRLR belongs to the class I cytokine
      receptor superfamily. Up to now, three membrane--PRLRs have been clarified. They
      are long form (LF), intermediate form (IF) and short form (SF) including SFla and
      SFlb. All PRLRs are derived from a primary transcript of common gene through
      alternative splicing mechanism. Although the extracellular domain (ECD) and the
      transmembrane domain (TD) of LF, IF and SF are equal, different isoforms of PRLR
      exert different function through different intracellular domain. It has been well
      documented that abnormity of PRLR is closely related to the pathogenesis,
      progression and prognosis of cancers including breast cancer. Several PRLR
      antagonists have been well designed and evidenced to have the potential to be
      important therapeutics.

PMID- 22582594
TI  - [Redox modification of protein thiols in the regulation of cardiovascular
      functions].

PMID- 22582595
TI  - [Biological effect and cellular mechanism of non-endoplasmic reticulum
      calreticulin].

PMID- 22582596
TI  - [Regulation and biological effect of alternative splicing of VEGF].

PMID- 22582597
TI  - [Research progress of induced pluripotent stem cells].

PMID- 22582598
TI  - [Progress in sarcoplasmic reticulum RyR2 in the regulation of vascular
      reactivity].

PMID- 22582599
TI  - [Musclin and insulin resistance].

PMID- 22582600
TI  - [New progress on epigenetic mechanisms of cardiology diseases].

PMID- 22582601
TI  - [CLC-K chloride channel in the thick ascending limb of kidney and Bartter's
      syndrome].

PMID- 22582602
TI  - [Sperm-specific calcium channel CatSper and its functional regulation].

PMID- 22582603
TI  - [The role of endoplasmic reticulum stress in insulin resistance of type 2
      diabetes].

PMID- 22582604
TI  - [Research developments on non-multidrug resistance function of P-glycoprotein].

PMID- 22582605
TI  - [The effect of psychoactive substances on expression of heat shock protein 70].

PMID- 22582606
TI  - [The role of Wnt/beta-catenin signal pathway in the myelination and
      remyelination].

PMID- 22582607
TI  - [Novel estrogen receptor GPR30/GPER1 and its role in breast cancer].

PMID- 22582608
TI  - [Research on inorganic explosive and its principal component with laser-induced
      breakdown spectroscopy].
AB  - Laser-induced breakdown spectroscopy is a technology that can be used for high
      speed, real time, multi-component, online, remote detection, and it has
      considerable superiority in explosives detection. In the present experiment,
      using 1 064 nm Q-switch laser beam as the resource, the authors investigated a
      common inorganic explosive (black powder) and one of its key components (KNO3),
      while choosing NaNO3 as the reference. We obtained the LIBS spectroscopy of these
      three samples in two surrounding atmospheres (air and Ar gas) at different time
      delay. And we analysed the change in line intensity ratio of N, O along with the
      increase in time delay, and found that the maximum of the value of O/N is
      obtained at time delay 596 ns.

PMID- 22582609
TI  - [Effects of laser wavelength on detection of metal elements in water solution by
      laser induced breakdown spectroscopy].
AB  - In the present paper, aiming at the problem of laser induced breakdown
      spectroscopy (LIBS) applyication in ocean detection, the effects of laser
      wavelength on the detection of Ca in water solution were investigated. The
      evolvement characteriza tion of electron density was studied by analyzing the
      time resolved spectra of the plasma. The experimental results show that the
      lifetime of plasma is about 1 200 and 600 ns respectively induced by 1 064 and
      532 nm laser. Based on the optical transmission characteristic and the LIBS
      experimental results, the dependence of needed laser energy before incidence into
      water E(iopt)(r) for optimal detection effect on the detection distance in water
      was found, and the dependence was simulated by applying to the in situ detection
      in water solution. The simulated results suggest that the needed laser energy of
      1 064 nm laser before incidence into water is about 100 mJ when the detection
      distance is no larger than 5 cm. When the detection distance increases to 10 cm,
      the needed laser energy of 532 nm before incidence into water is only about 30
      mJ. So it should be considered to choose 532 nm laser as the ablation source with
      the increase in the in situ detection distance.

PMID- 22582610
TI  - [Multi-harmonic analysis of quasi-continuous-wave laser modulation absorption
      spectroscopy].
AB  - Numerous harmonic components such as multiple frequency, sum frequency and
      difference frequency of multiple modulation signals were found in quasi
      continuous-wave (QCW) diode laser modulation absorption spectroscopy. Then, the
      authors analyzed these harmonic components' existence in terms of non-linear
      interactions of laser and gas absorption line. And the signals' characteristics
      were studied experimentally. The results shows that there are some sum frequency
      and difference frequency components that have larger amplitudes compared to the
      second harmonic wavelength modulation spectroscopy signal (2f-WMS) commonly used
      in tunable diode laser spectroscopy (TDLAS), and it may improve the detection
      sensitivity of QCW modulation spectroscopy.

PMID- 22582611
TI  - [Vibration-vibration energy transfer between highly vibrational excited RbH and
      H2, N2].
AB  - Rb-H2 mixture was irradiated with pulses of 696.4 nm radiation from a OPO laser,
      populating 6D state by two-photon absorption. The vibrational levels of
      RbH(X1sigma+,v" = 0-2) generated in the reaction of Rb(6D) with H2. Vibrational
      state-specific total-removal relaxation rate coefficients, k(v) (M), for
      RbH(X1sigma+, v" = 15-22) by M = H2 and N2 were investigated in a pump and probe
      configuration. By the overtone pumping with a cw diode laser, highly vibrational
      states v" = 15-22 of RbH in its ground electronic state were obtained. Another
      diode laser was used to probe the prepared vibrational state. The decay signal of
      laser induced time-resolved fluorescence from A 1sigma+ (v') --> X1sigma+ (v")
      transition was monitored. Based on the Stern-Volmer equation, the total
      relaxation rate coefficient k(v) (H2) were yielded. A plot of k(v) (H2 + N2) vs
      alpha (mole fraction H2) yields a line with a slope of k(v) (H2)-k(v) (N2) and an
      intercept of k(v) (N2). The values of k(v) (H2) obtained from the slope of the
      fitted lines compare well with determined values of the k(v) (H2) from the Sern
      Volmer plots. At v" < 18, the rate coefficients k(v) (M) increases linearly with
      vibrational quantum number. This linear region is dominated by single quantum
      relaxation (deltav = 1) collisional propensity rules. The region (v" > or = 18)
      where the dependence is much stronger than linear shows significant contribution
      from multiquantum (deltav > or = 2) relaxation or resonant vibration-vibration
      energy transfer between highly vibrationally excited RbH and H2 or N2. For
      RbH(v") + N2 (0), we measured the time-profile of v" = 16 after preparation of v"
      = 21. A clear bimodal distribution was observed. The first peak is due to
      resonant vibration-vibration energy transfer: RbH (v" = 21) + N2 (0) --> RbH (v"
      = 16) + N2 (1). The much broader second peak, at longer time delays, is due to
      sequential single-quantum relaxation. Although the second process results in a
      distribution that is much more spread out in time, the peak height is in the same
      order of magnitude, indicating that the two processes are at least comparable in
      probability.

PMID- 22582612
TI  - [Fast spectral modeling based on Voigt peaks].
AB  - Indirect hard modeling (IHM) is a recently introduced method for quantitative
      spectral analysis, which was applied to the analysis of nonlinear relation
      between mixture spectrum and component concentration. In addition, IHM is an
      effectual technology for the analysis of components of mixture with molecular
      interactions and strongly overlapping bands. Before the establishment of
      regression model, IHM needs to model the measured spectrum as a sum of Voigt
      peaks. The precision of the spectral model has immediate impact on the accuracy
      of the regression model. A spectrum often includes dozens or even hundreds of
      Voigt peaks, which mean that spectral modeling is a optimization problem with
      high dimensionality in fact. So, large operation overhead is needed and the
      solution would not be numerically unique due to the ill-condition of the
      optimization problem. An improved spectral modeling method is presented in the
      present paper, which reduces the dimensionality of optimization problem by
      determining the overlapped peaks in spectrum. Experimental results show that the
      spectral modeling based on the new method is more accurate and needs much shorter
      running time than conventional method.

PMID- 22582613
TI  - [Investigation of the vibrational temperature and gas temperature in gas
      discharge generated by plasma needle].
AB  - Low temperature plasma generated by plasma needle in atmospheric pressure air has
      extensive application prospects in industry because the vacuum device can be
      dispensable. In the present paper a stable plasma plume was generated in air by
      using a plasma needle device. The vibrational temperature and gas temperature
      were investigated for the plasma plume by optical spectroscopic method. Research
      results show that the plasma plume generated in atmospheric pressure air can be
      distinguished as a strong emission area near the needle followed by a weak
      emission area. The light emission signal from the discharge is a pulse per half
      cycle of the applied voltage with a time width of several microseconds. Results
      also indicate that the vabrational temperature varies from 2 500 to 3 000 K for
      different emission locations. The vibrational temperature increases with
      increasing the distance from the needle point in the strong emission area and it
      reaches a peak value at a distance of about 5mm from the needle point. The
      vibrational temperature decreases with increasing the distance from the needle.
      Similarly, the gas temperature decreases from 640K to 540K with increasing the
      distance from the needle point. These results are of great importance for the
      industrial applications of air discharge at atmospheric pressure.

PMID- 22582614
TI  - [Analysis of software for identifying spectral line of laser-induced breakdown
      spectroscopy based on LabVIEW].
AB  - Self-designed identifying software for LIBS spectral line was introduced. Being
      integrated with LabVIEW, the soft ware can smooth spectral lines and pick peaks.
      The second difference and threshold methods were employed. Characteristic
      spectrum of several elements matches the NIST database, and realizes automatic
      spectral line identification and qualitative analysis of the basic composition of
      sample. This software can analyze spectrum handily and rapidly. It will be a
      useful tool for LIBS.

PMID- 22582615
TI  - [Studies on signal-to-noise ratio standardization for THz time-domain
      spectroscopy].
AB  - In the present article the concept of standard signal-to-noise ratio (StSNR) for
      THz time-domain spectroscopy was introduced, with which different systems could
      be evaluated quantitatively. Based on the characteristics of SNR, a brief method
      was given for acquiring StSNR. With this method for calculating the StSNR, the
      result data of a single test was the only item needed, which eased the users lot
      to compare the capability of various THz time-domain spectrometers. According to
      this method, a number of THz-TDS systems applied in various THz research groups
      were evaluated.

PMID- 22582616
TI  - [Study on the optical properties of ultra-thin metal films in the THz band].
AB  - Thin metal films are good candidates of terahertz detectors, reflectors,
      waveguides and terahertz quantum-cascade lasers (THz-QCLs). The optical parameter
      is the basis not only for designing the THz components but also for developing
      novel optoelectronic materials. In the present paper, the complex refractive
      indices of the ultra-thin metal (Cr, Ni and Ti) films in the THz band were
      obtained by the THz differential time-domain spectroscopy. The reflection spectra
      of the GaAs/metals interface were calculated according to the Fresnel formula.
      The mean reflectance of 25 nm Cr, Ni and Ti are over 80% from 0.3 to 1.5 THz. The
      results show that ultra-thin metal films can be used for reflectors as well as
      the electrodes in the THz band.

PMID- 22582617
TI  - [Luminescence properties of Eu, Dy doped BaAl12 O19 long afterglow phosphors].
AB  - Long afterglow phosphors BaAl12 O19:Eu2+/Eu3+, Dy3+ were synthesized by high
      temperature solid state method under different atmosphere. X-ray powder
      diffraction (XRD) shows that pure BaAl12 O19 phase structure was obtained and the
      do ping ions Eu2+/Eu3+, Dy3+ didn't change the phase structure. By comparison,
      the authors found that the doping ions Eu2+/ Eu3+, Dy3+ caused the XRD
      diffraction peaks moving to the high angle slightly which displayed that the
      inter-planar spacing was changed via Eu and Dy replacing Ba lattice in BaAl12
      O19. Emission spectra show that all the samples prepared under different
      conditions exhibit the 4f6 5d1 --> 4J7 broadband transition which is the features
      emission of Eu2+ and the existence of the features emission of Eu2+ in the sample
      synthesized in air indicates that Eu3+ ions can be reduced to divalent state in
      air. The doping ions Dy3+ can not only enhance the luminous intensity of samples
      but also make the samples to obtain long afterglow characteristics. The afterglow
      decay and thermoluminescence studies of the Eu, Dy co-doped sample synthesized
      under reducing atmosphere reveal that the sample has good long afterglow
      properties at room temperature and high temperature.

PMID- 22582618
TI  - [Spectral analysis of LED excited organic material MPPV].
AB  - By the method of spin-coating, a glass was coated with a layer of organic
      material MPPV dissolved in organic solvent tetrahydrofuran (THF). The radios of
      MPPV: THF were 25 mg: 1 mL, 50 mg: 1 mL, 100 mg: 1 mL and 150 mg: 1 mL. Then we
      irradiated the organic thin film by blue and white LED. The results showed that
      the blue and white LEDs could excite the organic material MPPV to emit red light
      in the region of 600-750 nm. And with the increase in the organic material MPPV,
      the color coordinate moved from (0.265 4, 0.248 9) to (0.395 4, 0.288 0)
      gradually. When the ratio of MPPV: THF was 100 mg: 1 mL, the white LED had the
      best color-rendering index of 86.1. The minimum of color temperature reached
      2609K which was lower than that of white LED obtained by blue LED excited yellow
      YAG phosphor. Therefore, with the method of blue and white LED exciting the
      organic material MPPV, the color-rendering index and luminescence properties of
      LED could be improved significantly.

PMID- 22582619
TI  - [Luminescence properties of sodium chloride activated with Ce under vacuum
      ultraviolet excitation].
AB  - A series of NaCl : Ce3+ phospors were prepared by hydrothermal approach. The
      crystal structure was checked by X-ray diffraction, and the result showed that
      all the samples are of single phase. The VUV excitation and emission spectra were
      measured at room temperature. Two emission peaks at about 309 and 324 nm were
      obsereved and they were ascribed to 5d --> 4f (2F5/2, ZF7/2) transitions of. The
      excitation spectra contain two broad bands at 148 and 247 nm respectively. The
      peak at 148 nm can be attributed to the host related absorption and that at 190,
      205, 216, 232 and 247 nm is due to the 4f --> 5d transitions of Ce3+.

PMID- 22582620
TI  - [Ultraviolet Mie lidar observations of aerosol extinction in a dust storm case
      over Macao].
AB  - Atmospheric aerosol over Macao was monitored by using a 355 nm Mie scattering
      lidar during the dust event on March 22nd, 2010. Vertical profiles of aerosol
      extinction coefficients were obtained and correlated with local PM10
      concentration. The near-surface aerosol extinction coefficients have good
      agreement with PM10 concentration values. The aerosol extinction vertical
      profiles showed that there were distinct layers of dust aerosol concentration.
      The source and tracks of dust aerosol were analyzed by back-trajectory
      simulation. Observations showed that this lidar could run well even in dust storm
      episode, and it would help to further the study on aerosol properties over Macao.

PMID- 22582621
TI  - [FTIR analysis of the impact of covalent coupling on the secondary structure of
      antibody protein].
AB  - The immunolatex was prepared by covalent coupling. FTIR technology combined with
      substractive spectroscopy, deconvolution, derivation and curve-fitting methods
      were used to study the structure of the antibody protein on the immunolatex. The
      result demonstrates that the alpha-helix strcture of antibody increases with the
      increase in the pH value and the concentration of latex. So it is concluded that
      covalent coupling has a great impact on the secondary structure of antibody
      protein.

PMID- 22582622
TI  - [Analysis of the character of film decomposition of methyl methacrylate (MMA)
      coated urea by infrared spectrum].
AB  - The degradability characteristics of film with 4 kinds of methyl methacrylate
      coated urea amended with inhibitors were analyzed by FITR, which was purposed to
      supply theoretical basis for applying the FITR analysis method to film
      decomposition and methyl methacrylate coated urea fertilizers on farming. The
      result showed that the chemical component, molecule structure and material form
      of the membrane were not changed because of adding different inhibitors to urea.
      the main peaks of expressing film degradation process were brought by the -C-H of
      CH3 & CH2, -OH, C-O, C-C, C-O-C, C=O, C=C flexing vibrancy in asymmetry and
      symmetry in 3 479-3 195, 2 993--2 873, 1 741-1 564, 1 461-925 and 850-650 cm(-1).
      The peak value changed from smooth to tip, and from width to narrow caused by
      chemical structural transform of film The infrared spectrum of 4 kinds of
      fertilizers was not different remarkably before 60 days, and the film was slowly
      degraded. But degradation of the film was expedited after 60 days, it was most
      quickened at 120 day, and the decomposition rate of film was decreased at 310
      day. The substantiality change of film in main molecule structure of 4 kinds of
      fertilizers didn't happen in 310 days. The main component of film materials was
      degraded most slowly in brown soil. The speed of film degradation wasn't heavily
      impacted by different inhibitors. The characteristic of film degradation may be
      monitored entirely by infrared spectrum. The degradation dynamic, chemical
      structure change, degradation speed difference of the film could be represented
      through infrared spectrum.

PMID- 22582623
TI  - [Development of human blood glucose noninvasive measurement system based on near
      infrared spectral technology].
AB  - A small non-invasive measurement system for human blood glucose has been
      developed, which can achieve fast, real-time and non invasive measurement of
      human blood glucose. The device is mainly composed of four parts, i. e. fixture,
      light system, data acquisition and processing systems, and spectrometer. A new
      scheme of light source driving was proposed, which can meet the requirements of
      light source under a variety of conditions of spectral acquisition. An integrated
      fixture design was proposed, which not only simplifies the optical structure of
      the system, but also improves the reproducibility of measurement conditions. The
      micro control system mainly achieves control function, dealing with data, data
      storage and so on. As the most important component, microprocessor DSP
      TMS320F2812 has many advantages, such as low power, high processing speed, high
      computing ability and so on. Wavelet denoising is used to pretreat the spectral
      data, which can decrease the loss of incident light and improve the signal-to
      noise ratio. Kernel partial least squares method was adopted to build the
      mathematical model, which can improve the precision of the system. In the
      calibration experiment of the system, the standard values were measured by One
      Touch. The correlation coefficient between standard blood glucose values and
      truth values is 0.95. The root mean square error of measurement is 0.6 mmol x L(
      1). The system has good reproducibility.

PMID- 22582624
TI  - [Using infrared thermal asymmetry analysis for objective assessment of the lesion
      of facial nerve function].
AB  - The skin temperature distribution of a healthy human body exhibits a
      contralateral symmetry. Some lesions of facial nerve function are associated with
      an alteration of the thermal distribution of the human body. Since the
      dissipation of heat through the skin occurs for the most part in the form of
      infrared radiation, infrared thermography is the method of choice to capture the
      alteration of the infrared thermal distribution. This paper presents a new method
      of analysis of the thermal asymmetry named effective thermal area ratio, which is
      a product of two variables. The first variable is mean temperature difference
      between the specific facial region and its contralateral region. The second
      variable is a ratio, which is equal to the area of the abnormal region divided by
      the total area. Using this new method, we performed a controlled trial to assess
      the facial nerve function of the healthy subjects and the patients with Bell's
      palsy respectively. The results show: that the mean specificity and sensitivity
      of this method are 0.90 and 0.87 respectively, improved by 7% and 26% compared
      with conventional methods. Spearman correlation coefficient between effective
      thermal area ratio and the degree of facial nerve function is an average of
      0.664. Hence, concerning the diagnosis and assessment of facial nerve function,
      infrared thermography is a powerful tool; while the effective ther mal area ratio
      is an efficient clinical indicator.

PMID- 22582625
TI  - [Gemology characterization and identification of beryllium diffused, heated and
      untreated bicolor sapphires from Changle City, China].
AB  - Be-diffused, heated and untreated bicolor sapphires (blue and yellow) from
      Changle City, Shandong Province, China were studied by using standard gemological
      methods, ultraviolet-visible (UV-Vis) spectroscopy, infrared (IR) spectroscopy,
      electron microprobe, and laser ablation inductively coupled plasma mass
      spectrometry (LA-ICP-MS) to obtain the spectra characterization, and to suggest
      identification methods for them. Only Fe(3+)-Fe3+ absorption bands formed in
      ultraviolet region appear in Be-diffused bicolor sapphire, which is especially
      strong at 377 nm. In IR absorption spectra, absorption peak at 3 310 cm(-1)
      appears in heated and untreated bicolor sapphires, while it disappears in Be
      diffused bicolor sapphire. Therefore, UV-Vis and IR absorption spectra can be
      used to identify Be-diffused, heated and untreated bicolor sapphires. On the
      other hand, methylene iodide immersion observation also can be used to identify
      Be-diffused bicolor sapphire.

PMID- 22582626
TI  - [Application of near-infrared topology method in the quality analysis of jujube
      of southern Xinjiang].
AB  - In the present paper, both the physical characteristics and spectral signatures
      of southern Xinjiang jujube were studied. With the methods of repetitive
      adjustment and stepwise refinement, the analysis diagram of jujube quality
      subdivision and characteristic factors were obtained. In actual practice, the
      spectra repeatability and quality can be improved by setting an optimum
      acquisition parameter according to different experimental requirements. Through
      experiments the characteristic factors of crack browning, luster and compositions
      were obtained, which demonstrates a distinguishing downing characteristic
      spectral line at the wave number of 10 170 cm(-1). Through characteristic
      analysis of jujube NIR spectra, the correspondence between the jujube spectra and
      their qualities was established, which lays the foundation for jujube qualities'
      characteristic coding in the future. The application of near-infrared topology
      method in the quality analysis of southern Xinjiang jujube is cost saving, which
      has a broad application prospect in establishing the NIR analytical standard and
      model database sharing of the jujube's quality in the future.

PMID- 22582627
TI  - [Analysis of the 4th generation outer space bred Angelica dahurica by FTIR
      spectroscopy].
AB  - The major components of the 4th generation outer space bred angelica and the
      ground group were determined and analyzed by Fourier transform infrared
      spectroscopy (FTIR) and second derivative spectrum, considering the large
      mutation of the plants with space mutagenesis. The results show that the content
      of the coumarin (1741 cm(-1)), which is the main active components of the space
      angelica dahurica increased, and the content of the protein (1 459, 1 419 cm(-1))
      and the fat (930 cm(-1)) increased slightly, whereas the content of the starch
      and the dietary fiber reduced drastically. There are obvious differences between
      the peak values of the second derivative spectra of the plants, revealing that
      the outer space angelica dahurica contained amine component at 1 279 cm(-1).
      Space mutation breeding is favor of breeding angelica with better idiosyncrasy.

PMID- 22582628
TI  - [Research on characteristic of tobaccos from different ecological environments
      base on near infrared spectroscopy].
AB  - Four hundred ninety five samples from 3 parts of tobacco were collected from 11
      different ecological environments in 2010 to analyze the characteristics of
      tobaccos in different ecological environments with near infrared spectroscopy.
      The results indicate that the differences are remarkable both between lower and
      upper parts and between lower and middle parts of tobacco, while negligible
      between upper and middle parts of tobacco under the same ecological environment.
      Good stability and consistency were showed by the similarity of characteristics
      of tobaccos under different ecological environments, and the projection
      correlation coefficient of analysis set and validation set is over 98%. This
      article also proposes a method of measuring the similarity between
      characteristics of tobaccos from different ecological environments. The results
      can provide reference data to quantify tobacco's planting programming, production
      processing and quality management.

PMID- 22582629
TI  - [Research on Raman spectra of oxalic acid during decarboxylation under high
      temperature and high pressure].
AB  - The present research studied the thermal stability of oxalic acid under high
      temperature and pressure and its in-situ transformation by Raman spectroscopy
      using a hydrothermal diamond anvil cell. Raman spectra allow the detection of
      ionic and covalent atomic aggregates through the acquisition of vibrational
      spectra that are characteristic of their structures and molecular bond types. The
      result showed that there was no change in characteristic vibrational Raman peaks
      of oxalic acid in the low-temperature stage. With the increase in temperature and
      pressure, the characteristic vibrational Raman peaks of oxalic acid became weaker
      and the peaks disappeared at a certain high temperature, and decarboxylation
      happened. Oxalic acid decomposes to produce CO2 and H2, according to the
      reaction: C2 H2O4-2CO2 + H2. It was found that the decarboxylation was highly
      related with pressure and that the decarboxylation would be hindered at high
      pressure. Decarboxylation of oxalic acid under high temperature and pressure
      showed a linear relationship between temperature and pressure. The data fitting
      generated the formula: P(MPa) = 12. 839T(K)-5 953.7, R2 = 0.99. The molar volume
      change of decarboxylation of oxalic acid can be described by deltaV(cm(-3) x mol(
      1)) = 16.69-0.002P (MPa) + 0.005 2T(K), R = 0.99.

PMID- 22582630
TI  - [Raman spectroscopic study on the fluid effects in dissolution and phase
      transition mechanisms of gypsum].
AB  - Raman spectroscopic studies on the process of dissolution and phase transition of
      gypsum in different fluids were taken. Gypsum took phase transition to be
      anhydrite in the range from 170 degrees C to 190 degrees C in pure water, and no
      more change happened with decreasing temperature to room temperature. Gypsum took
      phase transition to be anhydrite in the range from 170 degrees C to 190 degrees C
      too in Na2 SO4 solution, but anhydrite can regain to be gypsum when temperature
      decreases to room temperature. The process of phase transition of gypsum in pure
      water is not reversible, but it happens in Na2 SO4 solution. The study shows that
      fluid effects can influence the dissolution and phase transition mechanisms of
      minerals and cannot be ignored.

PMID- 22582631
TI  - [Research on Raman spectra of isooctane at ambient temperature and ambient
      pressure to 1. 2 GPa].
AB  - The experimental study of the Raman spectral character for liquid isooctane
      (2,2,4-trimethylpentane, ATM) was con ducted by moissanite anvil cell at the
      pressure of 0-1.2 GPa and the ambient temperature. The results show that the
      Raman peaks of the C-H stretching vibration shift to higher frenquencies with
      increasing pressures. The relations between the system pressure and peaks
      positions is given as following: v2 873 = 0.002 8P+2 873.3; v2 905 = 0.004 8P+2
      905.4; v2 935 = 0.002 7P+ 2 935.0; v2 960 = 0.012P+2 960.9. The Raman spectra of
      isooctane abruptly changed at the pressure about 1.0 GPa and the liquid-solid
      phase transition was observed by microscope. With the freezing pressure at
      ambient temperature and the melting temperature available at 1 atm, the authors
      got the liquid-solid phase diagram of isooctane. According to Clapeyron equation,
      the authors obtained the differences of volume and entropy for the liquid-solid
      phase transition of isooctane: deltaV(m) = 4.46 x 10(-6) m3 x mol-1 and deltaS = 
      30.32 J x K(-1) x mol(-1).

PMID- 22582632
TI  - [Vibrational spectra of black species of hetian nephrite (tremolite jade) and its
      color genesis].
AB  - Black nephrite is a very uncommon jade type currently found only at Karakashi. In
      order to study the spectral characteristics and color-genetic mechanism of the
      black nephrite, samples collected from Karakashi were studied using EMPA, IR,
      Raman and XRD. The results are as follows: nephrite with different color has
      nearly the same major chemical compostions, while the black ones contain higher
      carbon; nephrite with different color has similar vibration spectrum, while the
      black ones show characteristic peak of graphite. It is speculated that the color
      of black nephrite is not only related with actinolite, but also related with the
      graphite inclusions. Obviously, Raman spectra is a very important nondestructive
      method to identify the color genesis and the origin of the black nephrite.

PMID- 22582633
TI  - [Study of surface enhanced Raman scattering of trace trinitrotoluene based on
      silver colloid nanoparticles].
AB  - Trinitrotoluene (TNT), a representative nitroexplosive, attracts more and more
      attentions because of the urgent demand for trace analysis of explosives in
      recent years. The present study investigated the experiment condition of the
      surface enhanced Raman scattering (SERS) of 10(-6) mol x L(-1) TNT solution,
      especially the influence of NaCl and basic hydrolysis. The results indicate that
      SERS spectra of TNT can not be obtained when preparing the SERS samples without
      NaCl, and it was also shown that the intensity of Raman peaks has a relationship
      with the concentration of NaCl. With the increase in the concentration of NaCl,
      the intensity of Raman peak at 1 392 cm(-1) has a maximum value. This report
      explained the reason why NaCl can affect the intensity of SERS theoretically. It
      was also shown that the SERS spectrum of TNT treated with basic hydrolysis is
      more intense than that without basic hydrolysis.

PMID- 22582634
TI  - [Variation of Raman spectra of oligoclase under 1.0-4.4 GPa].
AB  - Variation of crystal structure of oligoclase with pressure was investigated by
      the approach of diamond anvil cell (DAC) and in situ micro-Raman spectroscopic
      measurement at room temperature and under pressures from 1.0 to 4.4 GPa. At 2.9
      GPa a new peak round 517 cm(-1) appeared, and a new phase was produced. Near 3.4
      GPa a major discontinuity occurs in the pressure dependence of 288 cm(-1) peak
      arising from the stretching mode of M-O, and 517 cm(-1) peak disappeared, it
      implied that the oligoclase underwent triclinic to monoclinic phase transition
      completely at about 3.4 GPa. The peaks at 458 and 516 cm(-1) peaks arising from
      flexural vibrational mode of Si-O-Si shifted linearly with the increasing
      pressures, the pressure-related slopes are 1.667 cm(-1)/GPa and 3.560 cm(-1)/GPa,
      respectively, whereas, the flexural vibrational mode of Al-O-Al at 480 cm(-1) did
      not shifted linearly with the increasing pressures. The position of 288 cm(-1)
      peak did not change obviously in comparision with 458, 516 and 480 cm(-1) peaks,
      which shifted to lower frequency during decompression. The phase transition
      pressure of feldspar relates to the species of cation in the octatomic rings.

PMID- 22582635
TI  - [Analysis of pigments from Rhodotorula glutinis by Raman spectroscopy and thin
      layer chromatography].
AB  - The pigments from Rhodotorula glutinis were separated by using thin layer
      chromatography, and the result showed that Rhodotorula glutinis cells could
      synthesize at least three kinds of pigments, which were beta-carotene, torulene,
      and torularhodin. The Raman spectra based on the three pigments were acquired,
      and original spectra were preprocessed by background elimination, baseline
      correction, and three-point-smoothing, then the averaged spectra from different
      pigments were investigated, and the result indicated that Raman shift which
      represents C-C bond was different, and the wave number of beta-carotene
      demonstrated the largest deviation, finally torulene and torularhodin in
      Rhodotorula glutinis had more content than beta-carotene. Quantitative analysis
      of Raman peak height ratio revealed that peak height ratio of pigments showed
      little difference, which could be used as parameters for further research on
      living cells, providing reference content of pigments. The above results suggest
      that Raman spectroscopy combined with thin layer chromatography can be applied to
      analyze pigments from Rhodotorula glutinis, provides abundant information about
      pigments, and serves as an effective method to study pigments.

PMID- 22582636
TI  - [Study of aspirin and its interaction with DNA by Raman and UV spectroscopies].
AB  - Normal Raman spectroscopy and surface-enhanced Raman spectroscopy of aspirin and
      aspirin tablet were reported, and the vibrational and enhanced peaks were
      assigned; the interaction of aspirin with DNA was investigated by SERS and UV.
      The results showed that NRS and SERS of aspirin and aspirin tablet were
      consistent basically, which indicated that excipient hardly affected the
      detection of aspirin; in SERS, aspirin was absorbed perpendicularly on silver
      colloid through the carboxyl group and the benzene ring; The interaction was
      mainly caused by the inserting-action mode between aspirin and DNA, and the
      benzene ring and C=O of aspirin were inserted between the base pair of the double
      helix structure of DNA, which provided important information and useful reference
      for understanding deeply the mechanism of action of this kind of drug.

PMID- 22582637
TI  - [Optimization of melamine structure using density functional theory and
      vibrational spectra studies].
AB  - Melamine was used in foodstuff and feed industry as a feed additive occasionally.
      In the present work, melamine geometry structure was optimized by density
      functional theory (DFT) method. Raman and infrared spectra were calculated based
      on MP2/6-31G sets and DFT/DGTIVP sets, and then two theoretical Raman spectra
      were carefully compared with other experimental spectra. Good agreements were
      obtained between the theoretical and experimental results. Melamine structure
      parameters were given also in the paper including bond lengths and bond angles.
      Vibrational modes were assigned to all bands in the 550-4 000 cm(-1) range. This
      work will benefit the measurement research of the content of melamine in foods.

PMID- 22582638
TI  - [Excitation-emission matrix fluorescence spectra characteristics of DOM in a
      subsurface constructed wetland for advanced treatment of municipal sewage plant
      effluent].
AB  - Composition and dynamics of dissolved organic matter (DOM) were analyzed in a
      horizontal subsurface constructed wetland for advanced treatment of municipal
      sewage plant effluent using three-dimensional excitation emission matrix fluores
      cence spectroscopy (3D-EEM). The results indicate that the two subsurface
      constructed wetlands performed excellent purification of organic substances, and
      the removal rates of COD(cr), and DOC were 61.6% and 70.1%, respectively. The
      constructed wetland system filled with ceramsite showed slightly greater removal
      efficiency of organic substance than that with zeolite substrate. Four different
      types of peaks such as aromatic protein-like compounds (S), soluble microbial
      byproducts (T), fulvic acid-like compounds, visible fulvic-like (M) and UV fulvic
      like compounds (A) were found in DOM from inflow and outflow of the subsurface
      wetlands based on the three-dimensional fluorescence spectroscopy analysis. The
      fluorescence intensity of the four peaks was significantly decreased in the
      effluent after purification by the subsurface constructed wetlands. Especially,
      the visible fulvic-like compounds and soluble microbial byproducts were
      effectively removed from the sewage plant effluent by the subsurface constructed
      wetland with fluorescence intensity reduction percentages of 16.4% and 11.7%.
      Aromatic structures of humic-like compounds were weakened and organic compounds
      with benzene rings were decreased in the outflow of the subsurface constructed
      wetland. This indicates that the subsurface constructed wetlands can decompose
      the chemically stable and biorefractory humic-like compounds. The fluorescence
      intensity of M and T peaks decreased along distance, while the fluorescence
      intensity of S peaks firstly increased, then decreased along the distance of the
      subsurface constructed wetlands. As compared to zeolite substrate constructed
      wetland system, the constructed wetland system filled with ceramsite was more
      effective to reduce the fluorescence intensity of characterized peaks of DOM from
      the sewage plant effluent.

PMID- 22582639
TI  - [Application of PARAFAC method and 3-D fluorescence spectra in petroleum
      pollutant measurement and analysis].
AB  - A method for identification and concentration measurement of petroleum pollutant
      by combining three-dimensional (3-D) fluorescence spectra with parallel factor
      analysis (PARAFAC) was proposed. The main emphasis of research was the
      measurement of coexisting different kinds of petroleum. The CCl4 solutions of a
      0# diesel sample, a 97# gasoline sample, and a kerosene sample were used as
      measurement objects. The condition of multiple petroleum coexistence was
      simulated by petroleum solutions with different mixed ratios. The character of
      PARAFAC in complex mixture coexisting system analysis was studied. The spectra of
      three kinds of solutions and the spectra of gasoline-diesel mixed samples, diesel
      kerosene mixed samples, and gas oline-diesel mixed with small counts of kerosene
      interference samples were analyzed respectively. The core consistency diagnostic
      method and residual sum of squares method were applied to calculate the number of
      factors in PARAFAC. In gasoline-diesel experiment, gasoline or diesel can be
      identified and measured as a whole respectively by 2-factors parallel factors
      analysis. In diesel-kerosene experiment, 2-factors parallel factors analysis can
      only obtain the characters of diesel, and the 3rd factor is needed to separate
      the kerosene spectral character from the mixture spectrum. When small counts of
      kerosene exist in gasoline-diesel solution, gasoline and diesel still can be
      identified and measured as principal components by a 2-factors parallel factor
      analysis, and the effect of interference on qualitative analysis is not
      significant. The experiment verified that the PARAFAC method can obtain
      characteristic spectrum of each kind of petroleum, and the concentration of
      petroleum in solutions can be predicted simultaneously, with recoveries shown in
      the paper. The results showed the possibility of petroleum pollutant
      identification and concentration measurement based on the 3-D fluorescence
      spectra and PARAFAC.

PMID- 22582640
TI  - [Investigation of interaction between riboflavin and riboflavin binding protein
      by fluorescence spectroscopy].
AB  - The interaction between riboflavin and egg white riboflavin binding protein (RBP)
      was investigated using fluorescence spectroscopy. The binding mode, binding
      constants, thermodynamic parameters between riboflavin and RBP and energy
      transfer were studied. The experimental results showed that riboflavin has the
      ability to quench the intrinsic fluorescence of RBP because of a complex formed,
      and the quenching mechanism is static quenching. The binding constants were 5.35
      x 10(8), 1.54 x 10(8), 0.56 x 10(8) L x mol(-1) at 298, 308 and 318 K,
      respectively. The thermodynamic parameters were calculated, which suggested
      hydrogen bonds and Van der Waals played a major role in the interaction. The
      distance and efficiency of energy transfer between riboflavin and RBP were 0.70
      nm and 0.39, respectively, based on the theory of Forster nonradiative energy
      transfer. Furthermore, the synchronous fluorescence spectroscopy was utilized to
      investigate the conformational transformation.

PMID- 22582641
TI  - [Synthesis and characterization of mixed metal oxide pigments].
AB  - In the present work, aluminum chloride and various soluble salts of doping ions
      were dissolved in water. In addition, urea and polyvinyl pyrrolidone (PVP) were
      also dissolved in the above aqueous solution under supersonic treatments. Then
      the solutions were heated to induce the hydrolysis of urea so that soluble
      aluminum and doping ions convert into insoluble hydroxide or carbonate gels.
      After calcinations, the obtained gels change to mixed metal oxide pigments whose
      color is related to type and concentrations of the doping ions. XRD
      characterization demonstrates that the diffraction patterns of the products are
      the same as that of alpha-alumina. Diffuse reflectance spectra of samples of the
      samples in UV-Vis regions show that the absorption bands for d-d transitions of
      the doping ions undergo considerable change as the coordinate environments
      change. In addition, L*, a* and b* values of the pigments were measured by using
      UV-Vis densitometer. SEM results indicate that the size of the pigment powders is
      in the range 200-300 nm. The pigments are quite stable since no evidence of
      dissolution was observed after the synthesized pigment is soaked for 24 hours.
      ICP test shows that very little amount of doped metal occurs in the corresponding
      filtrate. The above results suggest that these new kinds of mixed metal oxide
      pigments are stable, non-toxic, environmental friendly and they may be applicable
      in molten spinning process and provide a new chance for non-aqueous printing and
      dyeing industry.

PMID- 22582642
TI  - [Partitioning of the suspended particulate spectral scattering coefficient in
      Poyang Lake].
AB  - A model for partitioning the particulate scattering coefficient into the
      contributions of suspended mineral particle and organic particle was proposed
      based on the measured data. The independent variables, i. e. the concentrations
      of mineral particles and organic particles in this study, were used to determine
      the mass-specific scattering cross section with the concurrent total suspended
      particulate scattering coefficients collected during the field trip in Poyang
      Lake 2009. Results show that the scattering spectra of inorganic particles and
      organic particles can be successful derived by the proposed model, and the
      reconstructed total particulate scattering coefficients are in better agreement
      with the measured values by the ordinary least square linear regression. For the
      whole South Poyang Lake, mean absolute percentage errors between the measured
      scattering coefficients and reconstructed value were less than 25% over the main
      remote sensing effective wavebands such as 440, 532, 555 and 676 nm. A remarkable
      lower predicted error, which can be controlled within 15%, were found at all
      stations with higher concentration of total suspended matters, while the spectral
      partitioning is less efficient at stations with total suspended particle
      concentration less than 15 mg x L(-1). Particulate scattering spectrum retrieved
      by RMA shows that illite and montmorillonite are the major constituents of
      inorganic matters which dominate the light scattering properties of Poyang Lake.
      It is possible that scattering spectrum partitioned by the model could infer the
      major effective components in waters, and could be used to predict particulate
      scattering properties for highly turbid waters.

PMID- 22582643
TI  - [Spectral analysis of the reaction of CH4 with CO2 as oxidant under plasma at
      atmospheric pressure].
AB  - The optical emission spectrometry (OES) of methane ranging from 200 to 900 nm
      under plasma with different carbon dioxide contents were recorded and marked.
      Various reactive species in methane plasma such as: CH(n) (n = 3, 2, 1), H, C2,
      C, C+, CO2+, O, CO+, OH and CHO were detected in situ by OES with different CO2
      contents at atmospheric pressure. The relative intensity of reactive species was
      different with different CO2 contents. The relative intensity of O reactive
      specie was increased rapidly and C2 reactive specie was reduced gradually with
      increasing CO2 contents. Reactive O from the dissociation of CO2 had an obvious
      influence on the methane conversion. The mechanism of methane conversion was
      changed when CO2 contents increased. The coupling of methane to C2 hydrocarbons
      was the main reaction when CO2 contents were smaller than 30%, while the
      reforming of methane played a dominant role when CO2 contents higher than 30%.

PMID- 22582644
TI  - [Effect of spectral resolution on black soil organic matter content predicting
      model based on laboratory reflectance].
AB  - Laboratory reflectance of Black soil samples was re-sampled with different
      spectral resolution, and the correlation between soil organic matter (OM) and
      reflectance, spectral variables was analyzed to study the effect of spectral
      resolution on black soil OM predicting model. The results are as follows: the
      spectral response range of black soil OM is between 445 and 1 380 nm, high OM
      content shades the spectral effect of other soil properties. The precision of
      black soil OM predicting models increases and decreases with spectral resolution,
      and the maximum accuracy is at 50 nm, which is wider than hyperspectral
      resolution, and narrower than the bandwidth of multispectral sensors; with the
      derivative of logarithmic reflectance reciprocal as input variables, the optimal
      black soil organic matter predicting model shows high accuracy, with R2 = 0.799
      and RMSE = 0.439; the results can provide the academic and technical support for
      soil organic matter remote sensing reversing and quick instrument developing.

PMID- 22582645
TI  - [Typical plant spectral characteristics analysis in wild duck lake along water
      environment gradient].
AB  - Typical submerged plants, floating plants, emerged plants, hygrophyte plants, and
      mesophyte plants were chosen, and derivative method and continuum removal method
      were used to analyze the spectral characteristics and changing trend of plants
      along water environment gradient. Emerged plants and hygrophyte plants have the
      highest reflectance value; floating plants have lower value, while submerged
      plants take the lowest reflectance value due to the effect of water surface.
      Derivative method could emphasize the changed trends of original spectral curve,
      thus more characteristic bands could take on. Spectral curves reached the fastest
      increasing points around 520 and 710 nm, which could be considered as
      characteristics bands to distinguish submerged plants and others. Emerged plants
      and hygrophyte plants have the peak green value. According to water environment
      gradient from high to low, the red edges of submerged plants, floating plants and
      emerged plants increase, while hygrophyte plants and mesophyte plants have lower
      red edge value. Original spectral curves were translated to absorption curves by
      continuum removal, the absorption depth changes from low to high as follows:
      submerged plants < floating plants < merged plants < hygrophyte plants, while
      that is lower for mesophyte plants compared to hygrophyte plants. Absorption area
      increased along water environment gradient from high to low except mesophyte
      plants.

PMID- 22582646
TI  - [Spectrometric characteristics and underlying mechanisms of protective effects of
      selenium on Spirulina platensis against oxidative stress].
AB  - To investigate the possibility and the underlying mechanisms of sodium selenite
      as antagonist for oxidative stress, the authors examined the effects of
      pretreatment with selenium on the growth, morphology, spectrometric
      characteristics and content of reactive oxygen species (ROS) in Spirulina
      platensis (S. platensis) exposed to H2O2 stress for 24 h in the present study.
      The results showed that H2O2 induced obvious inhibition of growth and serious
      morphological damage. The intensity of absorbance peak at 440 nm increased,
      whereas the peaks at 620 and 680 nm decreased after exposed to H2O2. The emission
      and excitation spectrum of S. platensis decreased dramatically after H2O2
      treatment, and the emission peak from phycocyanin exhibited blue-shift from 660
      to 650 nm. The results of FTIR analysis showed that the positions of transmission
      peaks had no shift, but the relative intensity of characteristic bands from
      protein and polypeptides including amide I and amide II decreased. Furthermore,
      the intracellular ROS generation in S. platensis increased significantly in
      response to H2O2 treatment. In contrast, pretreatments of the cells with selenium
      for 24 h significantly prevented the H2O2-induced oxidative damages in a dose
      dependent manner. Taken together, our results indicate that pretreatments with
      selenium could prevent ROS overproduction in S. platensis and improve its
      antioxidant ability. Moreover, selenium could also reduce the effects of free
      radicals on energy harvest and energy transfer in S. platensis that play vital
      roles in its photosynthesis.

PMID- 22582647
TI  - [Study on detection of changes in tissue structure and composition by using
      virtual internal hyper-spectrum of body surface].
AB  - Purposed to achieve the detection of changes in tissue structure and composition
      simultaneously by virtual internal hyper-spectrum of body surface (VIHBS), we
      designed the VIHBS system containing modulated light, translation stage device
      for data acquisition and spectrometer. In the present study, pork meat as the
      experimental subject was equally divided into three pieces. One piece was used
      for a control study, and the others were separately embedded with red filter and
      injected into highly scattering intralipid to imitate the changes in tissue
      structure and composition. And then, data acquisition of 17 points started at
      source fiber was taken at intervals of 0.5 mm. The results showed that modulated
      light can effectively inhibit the influences of ambient light and dark current
      created by optoelectronic devices. In addition, VIHBS technology achieved the
      locating of red filter by visible-light and the rapid screening of changes in
      tissue composition caused by intralipid with near infrared light. The study
      suggests that it is much feasible to detect the changes in tissue structure and
      composition by VIHBS. And it is concluded that further research will be likely to
      provide a new method to realize the early diagnosis and screening of human skin.

PMID- 22582648
TI  - [Method of fast and automated detection of diabetic retinopathy based on
      mathematical morphology].
AB  - The technology of automated detection of diabetic retinopathy (DR) on fundus
      retinal images can not only make mass screening possible, but also offer a
      powerful adjunct for early diagnosis, treatment of diabetic retinopathy, and
      scientific research on human vision. For this purpose, an algorithm based on
      mathematical morphology for automated detection of diabetic retinopathy was
      proposed. Firstly, the optic disc was segmented by mathematical morphology and
      threshold in order to find candidate regions possibly containing lesions.
      Secondly, some methods such as morphological reconstruction were applied to find
      the exact contours of lesions. Finally, the true lesions were found out exactly.
      Experimental results showed that the algorithm was fast and effective in
      detecting diabetic retinopathy of fundus retinal images.

PMID- 22582649
TI  - [Investigation of the enrichment and separation of lead and lead isotopes in
      simulated blood matrix].
AB  - The enrichment and separation method was used in the present paper to overcome
      the influence of matrix effect on the determination of lead concentration and
      isotope ratios. The patented method was used to enrich and separate the lead in
      simulated blood matrix; the lead concentrations and isotope ratios were
      determined by ICP-MS before and after enrichment and separation. The recovery
      rate of Pb is more than 99% through this method while the removal rate of major
      impurity ions such as Na, K is about 80%. The concentrations of each lead isotope
      decrease with the matrix concentration increasing (p < 0.001), and lead isotope
      ratios show no significant differences in the matrix of different concentrations.
      When the matrix concentration is more than 62.5 microg x mL(-1), the strength
      will decrease with the determination times increasing. It was concluded that the
      characteristics of this method are of high recovery rate (> 99%), fast, simple
      and convenient, and it can raise the accuracy and precision of the concentration
      determination of lead isotopes and has no significant influence on the accuracy
      of lead isotope ratios determination.

PMID- 22582650
TI  - [Study on the experimental application of floating-reference method to
      noninvasive blood glucose sensing].
AB  - Weak signal, low instrument signal-to-noise ratio, continuous variation of human
      physiological environment and the interferences from other components in blood
      make it difficult to extract the blood glucose information from near infrared
      spectrum in noninvasive blood glucose measurement. The floating-reference method,
      which analyses the effect of glucose concentration variation on absorption
      coefficient and scattering coefficient, gets spectrum at the reference point and
      the measurement point where the light intensity variations from absorption and
      scattering are counteractive and biggest respectively. By using the spectrum from
      reference point as reference, floating-reference method can reduce the
      interferences from variation of physiological environment and experiment
      circumstance. In the present paper, the effectiveness of floating-reference
      method working on improving prediction precision and stability was assessed
      through application experiments. The comparison was made between models whose
      data were processed with and without floating-reference method. The results
      showed that the root mean square error of prediction (RMSEP) decreased by 34.7%
      maximally. The floating-reference method could reduce the influences of changes
      of samples' state, instrument noises and drift, and improve the models'
      prediction precision and stability effectively.

PMID- 22582651
TI  - [The monitoring of haze from HJ-1].
AB  - With the urbanizing in China, haze days occur frequently, which have largely
      impacted air quality. In the present paper, based on haze physical properties,
      haze optical properties were calculated by Mie theory and apparent reflectance of
      haze in Environment Satellite 1 (HJ-1) channels was simulated by Radiative
      Transfer (RT) 3. Simulated results show that it is reasonable to extract the haze
      from apparent reflectance in the first and second channels. By Deep Blue
      algorithm, Haze Optical Depth (HOD) was retrieved from HJ-1 data supported by
      reflectance database from MODIS product. From HJ-1 data in 2009 over Beijing
      area, the haze days were monitored and validated by AERONET/PHOTONS Beijing site.
      The validation shows that the correlation coefficient of HOD is greater than 0.9,
      but HOD from HJ-1 is greater than that from ground-based measurements. The
      discussions show that the error from reflectance database is less than 0.1 and
      radiance resolution of HJ-1 needs to advance for haze monitoring.

PMID- 22582652
TI  - [Spatial resolution standardization of payload on board of remote sensing
      satellite based on application requirements].
AB  - Remote sensing application requirements are the starting point for design of
      payload on board earth observation satellite. The generalization, standardization
      and serialization of payload are the future development trend for payload design.
      In the present paper, based on the analysis of remote sensing application
      requirements, the spatial resolution standardization of satellite remote sensing
      payload, which is the main concerned indicator, was investigated. The design
      standards of national payload spatial resolution of earth observation satellite
      are presented, which are important to the promotion of satellite payload
      production and saving in design cost.

PMID- 22582653
TI  - [Analysis of the effect of detector's operating temperature on SNR in space-based
      remote sensor].
AB  - Limb viewing is a new viewing geometry for space-based atmospheric remote
      sensing, but the spectral radiance of atmosphere scattering reduces rapidly with
      limb height. So the signal-noise-ratio (SNR) is a key performance parameter of
      limb remote sensor. A SNR model varying with detector's temperature is proposed,
      based on analysis of spectral radiative transfer and noise' source in
      representative instruments. The SNR at limb height 70 km under space conditions
      was validated by simulation experiment on limb remote sensing spectrometer
      prototype. Theoretic analysis and experiment's results indicate congruously that
      when detector's temperature reduces to some extent, a maximum SNR will be
      reached. After considering the power consumption, thermal conductivity and other
      issues, optimal operating temperature of detector can be decided.

PMID- 22582654
TI  - [Advance in the study of the powdered weathering profile of sandstone on China
      Yungang Grottoes based on VIS/NIR hyperspectral imaging].
AB  - Yungang Grottoes were built in the mid-5th century A. D., and named as a UNESCO
      World Heritage site in 2001. Most of the grottoes were built on the feldspathic
      quartz sandstones. They were seriously damaged due to the environmental impact.
      The main form of the weathering is the powdered weathering. The weathering
      conditions are generally characterized by electrical sounding, penetration
      resistance, molecular spectroscopy, etc. However, although these methods can give
      good results about the weathering conditions for a specified sample or site, they
      are not suitable for providing a global profile of the weathering conditions. The
      present paper provides a method for effectively and roundly assessing the overall
      powdered weathering conditions of the Yungang Grottoes based on hyperspectral
      imaging. Powdered weathering could change the structure and granularity of the
      sandstone, and thus change the spectral reflectance of the sandstone surface.
      Based on the hyperspectral data collected from 400 nm to 1 000 nm and normalized
      by log residuals method, the powdered weathering conditions of the sandstones
      were classified into strong weathering and weak weathering. The weathering
      profile was also mapped in the Envi platform. The mapping images were verified
      using the measured hyperspectal data of the columns in front of the 9th and 10th
      grottoes as the examples. The mapping images were substantially fitted to the
      real observations, showing that hyperspectral imaging can be used to estimate the
      overall powdered weathering of the sandstones.

PMID- 22582655
TI  - [Feasibility of composition analysis of complex mixed solution by hyperspectral
      technique].
AB  - The complex mixed solution is a common material form in all walks of life. It was
      difficult to achieve the desired results if the complex mixed solution was
      detected by the traditional spectral analysis method. The hyperspectral
      technology was taken to detect the complex mixed solution to improve the signal
      to noise ratio of the spectrum by utilizing the absorbing and scattering
      characteristics of the analytes at the same time. A hyperspectral acquisition
      device was designed to collect the diffuse reflectance hyperspectral images of
      the analytes (Intralipid-10%). The Monte Carlo simulation and the diffuse
      approximation were used to validate the experimental device. The authors found
      that the absorption coefficient of the Intralipid-10% at 632 nm was 0.002 0 cm(
      1) and the reduced scattering coefficient was 63.35 cm(-1); the corresponding
      relative error of the standard reference was 11.1% and 6.49%. The inversion
      result of the diffuse approximation validated the exactness of the experimental
      device. Finally, the hyperspectral images of milk and fruit juice from different
      manufacturers were taken, the images show that the differences between different
      samples were more obvious than that of traditional 2-dimensional spectrum. This
      research reveals that the hyperspectral technology is feasible in the component
      analysis of complex mixed solution.

PMID- 22582656
TI  - [Nonlinear spectral imaging of DNA specimens derived from tumor cells based on
      second harmonic generation].
AB  - Second harmonic generation (SHG) is a second-order nonlinear optical process that
      has symmetry constraints confining signal to regions lacking a center of
      symmetry. Using SHG microscopy, a variety of tissue structures have noninvasively
      been imaged by virtue of intrinsic signal generated by structured proteins such
      as collagen fibrils in connective tissues or the actomyosin lattice of muscle
      cells. In biochemistry and structure biology, the high-level structures of DNA
      and protein macro-molecules are similar in constructing mechanism, although DNAs
      consist of deoxynucleotides and proteins of amino acid residues. The principal
      purpose of present work is to detect the SHG signal from different DNA samples by
      spectral imaging technology based on two-photon excited fluorescence (TPEF) and
      SHG. These DNA samples include the solution of genomic DNA and extracted nuclei,
      and cultured living cells. Results show that we can obtain the SHG signal from
      solution of genomic DNA and extracted nuclei in routine condition, but nothing
      from cultured cell nuclei. After adding a little of absolute ethanol (less than
      5% by volume) in culture medium, the SHG signal is detectable in the interested
      region of nuclei. The findings suggest that the interaction between ethanol and
      DNA in living cell gives rise to the shift of molecular conformation, and this
      shift changes some nonlinear optical properties of DNA molecules.

PMID- 22582657
TI  - [Synthesis and spectral studies of nickel(II) complex of 2,6-bis [N-(1,1'
      dimethyl-2'-hydroxy) carbamoyl]pyridine].
AB  - The ligand of 2,6-bis[N-(1,1'-dimethyl-2'-hydroxy)carbamoyl]pyridine and its
      nickel(II) complex were synthesized and characterized by using 1H-NMR, 13C-NMR,
      FTIR, UV-Vis and elemental analysis, and the complex formulae of C15 H21 N3O4 Ni
      x H2O were determined. The spectral property of the free ligand and its
      nickel(II) complex was discussed with the comparison method, and then the
      structure of nickel(II) complex was determined. The spectral analysis results
      show that 2,6-bis[N-(1,1'-dimethyl-2'-hydroxy)carbamoyl] pyridine acts as a
      tridentate ligand, coordinating through two nitrogen atoms of amide anion and one
      nitrogen atom of aromatic pyridine-ring, and the nickel(II) ion is a four
      coordinated geometry with dsp2 hybrid orbitals for bonding these coordinating
      atoms. The target complex is a square planar low-spin nickel(II) coordination
      compound, and a nickel(II) ion coordinates to a tridentate ligand and one
      coordination water molecule.

PMID- 22582658
TI  - [Determination of 9 heavy metal elements in sediment by ICP-MS using microwave
      digestion for sample preparation].
AB  - A method for determining 9 heavy metal elements in soil and sediment was
      developed by using microwave digestion-ICP-MS. The mixture of HNO3-H2O2-HF was
      found to give the best digestion results for soil and sediment of samples. Under
      the optimized conditions, the samples were analyzed by ICP-MS with the triple
      internal standard elements Ge, In and Bi. The results showed that all their
      correlation coefficients were over 0.999. The national standard soil referenee
      material (ESS-1 GSBZ50011-88) was analyzed by the described method and the
      results were accorded with the reference values. The measurement precision range
      was from 0.48% to 5.73% in terms of relative standard deviation. The recoveries
      and the limits of detection were in the ranges of 98.0% to 100.7% and 0.011 to
      0.328 microg x L(-1) respectively, and 11 sediment samples were determined by the
      proposed method. It was indicated that the method was reliable for determining
      heavy metal elements in soil and sediment samples.

PMID- 22582659
TI  - [Determination of arsenic, mercury and selenium in Gynostemma pentaphyllum and
      rhizospheric soil samples collected from different regions by hydride generation
      atomic fluorescence spectrometry].
AB  - The contents of arsenic (As), mercury (Hg) and selenium (Se) in Gynostemma
      pentaphyllum and rhizospheric soil samples collected from seven provinces were
      determined, through the optimization of the hydride generation atomic
      fluorescence spectrometry working conditions. The results show that: the contents
      of As, Hg and Se in Gynostemma pentaphyllum from seven provinces revealed large
      differences, but compared with the limits of the two kinds of heavy metal
      element: As and Hg set by the Green Trade Standards of Importing & Exporting
      Medicinal Plants & Preparations (As < or = 2.0 mg x kg(-1), Hg < or = 0.2 mg kg(
      1)), the As and Hg contents in Gynostemma pentaphyllum samples are both lower
      than them. The Se content in Gynostemma pentaphyllum samples and in rhizospheric
      soil samples revealed significant correlation, and as a result, the Gynostemma
      pentaphyllum from the Fu Xi area Enshi in Hu Bei province had obviously higher Se
      content than others in the 6 provinces. From this study, a preliminary conclusion
      can be drawn that Se in Gynostemma pentaphyllum is mainly from the soil,
      moreover, the As and Hg show the difference from Se, possibly they are still
      affected by the dry and wet deposition of atmospheric aerosols.

PMID- 22582660
TI  - [FI-KR non-separated method coupled with FAAS for the determination of Fe(II) and
      Fe(III) in water].
AB  - An FI-KR non-separated method coupled with FAAS for the determination of Fe(II)
      and Fe(III) was developed. With 60 s of sampling at a flow rate of 6.0 mL x min(
      1), EF of 41 for Fe(III) and 9 for Fe(II) were obtained. The precision (RSD, n =
      11) for Fe(III) and Fe(II) was 2.3% and 3.1% at the 0.04 mg x L(-1) level
      respectively. When 0.1 per thousand phi TEA was used as masking reagent, the
      recovery rate for Fe(III) and Fe(II) was from 97% to 101% and from 96% to 100%
      respectively.

PMID- 22582661
TI  - [In vivo determination of Pb in human bone by using X-ray fluorescence analysis].
AB  - The data of in vivo XRF Pb in human bone were obtained within China by using the
      in vivo XRF set. The K series X-ray of Pb were applied to determine the in vivo
      Pb concentration in tibia and calcaneus among Chinese mainland residents. For
      general population, the weighted average of Pb in bone was 0.4-22.7 microg x
      (lead g bone mineral)(-1). The uncertainty was 7.0-12.5 microg x (lead g bone
      mineral)(-1), and the average minimun detection limit was 20.3 microg x (lead g
      bone mineral)(-1). For residents from pollution area, the maximum Pb in bone
      reached up to 73.9 microg x (lead g bone mineral)(-1).

PMID- 22582662
TI  - [Analysis of heavy metal in soil with portable X-ray fluorescence spectrometry].
AB  - The concentrations of main heavy metal pollutants (Cu, Zn, Pb, Cr and As) in soil
      were tested by NITON XL3 600 portable X-ray fluorescence spectrometry (PXRF). The
      results showed that the minimum? detection limits for elements Cu, Zn, Pb, Cr and
      As were 23.96, 11.69, 8.58, 19.23, 6.24 mg x kg(-1), respectively. The soil
      composition standard material GSS-5 was detected by PXRF for 5 replicate
      measurements, The accuracy was 96%-102% and relative standard deviations (RSD)
      was 1.0%-7.6%. In term of field situ testing, RSD was less than 20%, and accuracy
      was 55%-119%. The performance was assessed by laboratory testing and field situ
      detection, and the results indicated that PXRF is effective for rapid,
      quantitative monitoring of soil metal contamination.

PMID- 22582663
TI  - [Optical system design of plane grating double monochromator].
AB  - The plane grating double monochromator is the important part of the instrument
      for testing diffraction efficiency of plane grating, and in order to accomplish
      the research of the instrument, the optical system design and simulation of the
      plane grating double monochromator was investigated. The instrument mainly
      consists of light source, front monochromator, testing monochromator and
      detector, and combined with the practical requirement, the corresponding light
      source, detector and the structure of the optical path were selected. According
      to the design requirement, the design and simulation of the optical system of the
      front monochromator and testing monochromator were done respectively, and the
      spot diagram of the image surface and the results of real ray trace were given.
      The analysis showed that in the front monochromator the maximum width of the exit
      spot and the maximum height of the exit spot were 0.33 and 1.83 mm respectively.
      On the other hand, in the testing monochromator, the maximum width of the exit
      spot and the maximum height of the exit spot were 0.66 and 7.27 mm, respectively.
      Through selecting the size of the exit slit properly, the system can work without
      luminous flux lost, which guarantees the testing precision of the optical system
      of the instrument.

PMID- 22582664
TI  - [Design of optical system for solar extreme-ultraviolet imaging spectrometer].
AB  - Hyper-spectral imaging observation of the sun in the EUV region is an important
      method of research for solar's upper transition region, corona and plasma's
      physical property. Based on the application objective of solar extreme
      ultraviolet imaging spectrometer (SEUIS), combined with the current states of
      domestic and foreign extreme ultraviolet imaging spectrometer, a few of
      parameters for SEUIS design were drew up in the present paper. The advantages and
      disadvantages of all kinds of optical configurations were discussed,and the
      configuration of combination of telescope and spectrometer was chosen. The
      available main components were also described, off-axis parabolic mirror was
      chosen for telescope, and a high density uniform-line-space toroidal grating for
      dispersion device. The optical system which satisfies the performance parameters
      was designed. The design process, detailed parameters and results were presented
      in the end. The working wavelength of the optics system is 17.0-21.0 nm, the
      field of view is 1 228" x 1 024", the spatial resolution is 0.8 arc sec x pixel(
      1), the spectral resolution is about 0.00198 nm x pixel(-1), and the total length
      of system is about 2.8 m.

PMID- 22582665
TI  - [The integrative design for imaging spectrometer].
AB  - The hyperspectrum imaging spectrometer will achieve miniaturization and high
      spectrum resolution and high space resolution along with development of the
      hyperspectrum imaging technology that is becoming a trend. This trend requires
      the designers to improve and optimize their designing constantly in designing the
      instruments. The present paper carried out a method of integrative design for
      imaging spectrometer. This method suggested that the design and optimization work
      of the disperse systems of imaging spectrometers would take into account the
      whole systems, but not consider themselves only. It would get a perfect result by
      using this method. This paper also explained in details how the method can be
      used in the design course of imaging spectrometer with convex grating which has
      been used widely recently. Finally, this paper validated the method by testing
      the imaging spectrometer with convex grating, which was developed using this
      method.

PMID- 22582666
TI  - [Study on far ultraviolet imaging spectrometer with grating dispersion for
      atmosphere remote sensing].
AB  - The far ultraviolet imaging spectrometer with grating dispersion is mainly used
      in the detection of the ionosphere, thermosphere, auroral zone and glow zone. It
      is important for the study and application of the remote sensing of atmosphere in
      China. We designed two optical systems for the far ultraviolet imaging
      spectrometer, and obtained the plane grating structure prototype based on the
      principles of nadir and limb atmospheric sounding. The prototype working at the
      waveband of 120-180 nm consists of an off-axis parabolic mirror and an advanced
      Czerny-Turner spectral imaging system. The far ultraviolet response back
      illuminating CCD is adopted as the detector. The corresponding experiment system
      was built to calibrate the basic performances of the spectrometer prototype. The
      spectral and spatial resolutions are 2 nm and 0.5 mrad respectively. The far
      ultraviolet imaging spectrometer prototype plays an important role in the study
      and application of atmospheric remote sensing.

PMID- 22582667
TI  - [Position acquiring of signal spots in the echelle spectrograph].
AB  - It is important for the echelle spectrograph to acquire the exact positions of
      the spots in the two-dimension spectra image, which directly influence the
      precision of spectral analysis. With the target of high resolution, which is 15
      000 in the echelle spectrograph being discussed, the acquired positional error
      must be less than 0.03 mm-which equals 2 pixels. According to the characters of
      the two-dimensional spectra, a position-acquiring method for the signal spots
      based on the centroid computing algorithm was put forward. Applying this method,
      the signal spots were distinguished from the noise spots and their positions can
      be acquired accurately and swiftly, with the positional error less than 2 pixels
      and wavelength error 0.02 nm, which satisfy the requirements of the echelle
      spectrograph.

PMID- 22582668
TI  - [Design and experiment of micro biochemical detector based on micro
      spectrometer].
AB  - According to the requirements of rapid detection of important life parameters for
      the sick and wounded, a new micro bio-chemical detection configuration was
      proposed utilizing continuous spectroscopy analysis, which was founded on MOEMS
      and embedded technology. The configuration was developed as so much research work
      was carried out on the detecting objects and methods. Important parameters such
      as stray light, absorbance linearity, absorbance ratability, stability and
      temperature accuracy of the instrument were tested, which are all in good
      agreement with the design requirements. Clinic tests show that it can detect
      multiple life parameters quickly (Na+, GLU, Hb eg.).

PMID- 22582669
TI  - [Design of a controllable low temperature cell and application].
AB  - A new cryogenic cell was developed and could operate at any stabilized
      temperature ranging from room temperature down to 100 K with temperature
      fluctuation less than +/- 1 K. The structure and performance of the cryogenic
      cell was given in detail and the temperature stability of the sample cell was
      evaluated. The methane low temperature absorption spectra at 1.65 microm were
      recorded at 296, 248, 198 and 176 K and while the characteristic of methane low
      temperature absorption spectra at 6 039.70 cm(-1) was given. According to the
      characteristic of our cryogenic cell, we measured the temperature-dependent
      exponent n of self-broadening coefficient at 6 039. 657 9 cm(-1).

PMID- 22582670
TI  - Reading times and adaptive styles among patients diagnosed with psychosis as
      assessed by the Serial Color-Word Test.
AB  - The present study focuses on how patients diagnosed with psychosis deal with a
      conflicting situation. In the study, two groups of patients were assessed. One
      group consisted of patients diagnosed with psychosis (n = 41), while the
      comparison group (n = 135) consisted of inpatients diagnosed either with anorexia
      nervosa or with bulimia nervosa. The groups were assessed using the Serial Color
      Word Test (S-CWT), designed for studying an individual's successive adaptation
      over time to a conflicting situation. The S-CWT differentiated the two groups
      regarding both reading time and adaptive styles. Patients diagnosed with
      psychosis had longer reading times and an adaptive style that was deviant
      throughout the test, indicating poorer cognitive functioning and more serious
      psychopathology. These problems may in turn influence functioning in work or
      study and daily living, all of which are important in treatment planning.

PMID- 22582671
TI  - Twenty-year trends of authorship and sampling in applied biomechanics research.
AB  - This study documented the trends in authorship and sampling in applied
      biomechanics research published in the Journal of Applied Biomechanics and ISBS
      Proceedings. Original research articles of the 1989, 1994, 1999, 2004, and 2009
      volumes of these serials were reviewed, excluding reviews, modeling papers,
      technical notes, and editorials. Compared to 1989 volumes, the mean number of
      authors per paper significantly increased (35 and 100%, respectively) in the 2009
      volumes, along with increased rates of hyperauthorship, and a decline in rates of
      single authorship. Sample sizes varied widely across papers and did not appear to
      change since 1989.

PMID- 22582672
TI  - Metronome rate and walking foot contact time in young adults.
AB  - It is assumed that when people walk guided by an audible constant rate, they
      match foot contact to the external pace. The purpose of this preliminary study
      was to test that assumption by examining the temporal relationship between
      audible signals generated by a metronome and foot contact time during gait. Ten
      healthy young women were tested in walking repetitions guided by metronome rates
      of 60, 110, and 150 beats/min. Metronome beats and foot contact times were
      collected in real time. The findings indicated that foot contact was not fully
      synchronized with the auditory signals; the shortest time interval between the
      metronome beat and foot contact time was at the prescribed rate of 60 beats/min.,
      while the longest interval was at the rate of 150 beats/min. The correlation
      between left and right foot contact times was highest with the slowest rate and
      lowest with the fastest rate.

PMID- 22582673
TI  - Object and size awareness in preschool-age children.
AB  - Self-awareness is a skill developed during the first few years of life. Although
      some research demonstrates that this ability may be incomplete in toddlers, there
      is little to no literature relating to preschoolers. This study tested 44
      preschool-age children on 8 tasks to assess their awareness of the structural
      characteristics of their own size and weight as well as the size and weight of
      external objects. The most frequently observed behavior was for children to make
      an attempt at something that was inappropriate for their size and weight, but
      overall participants showed a better understanding of their own bodies than other
      objects. Both the number of attempts required to solve the problems and accuracy
      of their solutions demonstrated these task differences. These results indicate
      that the development of body awareness skills is far from complete for 3- and 4
      year-olds.

PMID- 22582674
TI  - College students' style of language usage: clues to creativity.
AB  - The current study aimed to provide initial quantitative data on the relationship
      between college students' style of language usage and their creativity.
      Correlation coefficients between Alternative Use Test creativity scores and
      Korean Linguistic Inquiry and Word Counts were calculated from 157 college
      students' stream of consciousness writings. The results showed that people who
      scored as more creative also used more content words to express their thoughts,
      and they did so in a more straightforward manner. The results also showed that
      these people used a greater number of concepts that were more abstract, had a
      more individualistic perspective, and thought in less conventional ways. This
      study provides reference data for future studies on the relationship between
      creativity and language usage.

PMID- 22582675
TI  - Cognitive style in attainment of an upside-down posture in water with and without
      vision.
AB  - It is well known that adopting a posture required by the central nervous system
      takes into account a frame of reference. This frame of reference is built on
      sensory information and, more particularly, on vision, which is often considered
      to be the main input. The contribution of vision varies by participant and
      defines their cognitive style. This study investigates the contribution of visual
      information and cognitive style to postural strategy and, more precisely, to the
      construction of an upside-down posture in an underwater condition. Eight
      synchronized swimmers performed the Rod-and-Frame Test (RFT) to assess their
      cognitive style and practiced upside-down posture in water to measure their body
      inclination. The Rod-and-Frame Test scores did not distinguish the participants,
      as the results of the test showed that most of them were visual-field
      independent. However, in a closed-eyes condition, participants achieved a more
      precise vertical position than when using translucent goggles.

PMID- 22582676
TI  - Development and use of a computerized test, MATH-CPT, to assess attention.
AB  - The present research describes the development of a new measure of attention, the
      Mathematics Continuous Performance Test (MATH-CPT), which uses a sequence of
      simple mathematical questions projected onto a computer screen as visual stimuli.
      A new approach to testing was developed: it has more complicated stimuli and has
      an open reaction time allowing participants to react according to individual
      pace. The development of reliability and validity of the MATH-CPT is described.
      Discriminant function analysis of 240 normal control participants compared with
      63 individuals with ADHD showed correct classification of 91.6% of participants
      in both groups. The MATH-CPT diagnosed a sample of participants with ADHD better
      than another CPT-type test, the Test of Variables of Attention. This is an
      initial step in developing a new measure of attention and to assist with the
      diagnosis of adolescents and young adults with ADHD.

PMID- 22582677
TI  - Psychometric analysis of five measures of spatial ability.
AB  - This study analyzed psychometric properties of five measures of spatial ability
      on 96 young adults, with supplementary analysis for three of the measures on
      another sample of 71 young adults. Two measures were taken from the widely cited
      Kit of Factor-Referenced Cognitive Tests and three other measures were taken from
      a relatively new source originally intended as laboratory demonstrations.
      Previous research provided limited information on the psychometric properties of
      the measures. All five measures yielded adequate reliability and loaded on a
      single factor. Three measures yielded markedly skewed distributions. Two measures
      showed clear sex differences with men scoring higher but this difference seemed
      contaminated by a speed factor; three measures did not show a sex difference.
      Recommendations for use of the measures in future studies are provided.

PMID- 22582678
TI  - Head movements while steering around bends.
AB  - In this study, the determinants of head motions (rotations) when driving around
      bends were investigated when drivers viewed the scene through a head-mounted
      display. The scene camera was either fixed or coupled to head motions along 2 or
      3 axes of rotation. Eight participants drove around a triangular circuit and the
      range and speed of head rotations, the correlations between head rotations and
      lateral acceleration, and the coupling between the different axes of head
      rotation were calculated. Results showed that substantial head rotations were
      made even when head rotations had no influence on the direction of the camera,
      suggesting a strong motor coupling between steering actions and head motion. Head
      roll was determined, at least in part, by the gravito-inertial force,
      contradicting earlier results reported in the literature.

PMID- 22582679
TI  - A comparison of ultra-endurance cyclists in a qualifying ultra-cycling race for
      Paris-Brest-Paris and Race Across America-Swiss cycling marathon.
AB  - Ultra-endurance events test the adaptation of human physiology to extreme
      physical and mental demands, high levels of training, motivation, and physical
      conditioning among participants. To understand basic differences among
      participants according to the severity of the race, participants in qualifying
      events for two ultra-endurance cycling races, differing in length and intensity,
      were compared on measures of anthropometry, training, and support. One race was
      four times longer, required supporting teams, and racers typically had little
      sleep, which should lead to the qualifiers being substantially more highly
      trained than those from the shorter race. The qualifiers in the longer race had
      greater intensity in training while the qualifiers in the shorter race relied
      more on training volume. Different strategies and types of training reflected the
      different demands of the races. Future studies should evaluate personality and
      motivational differences in ultra-endurance events and between these athletes and
      athletes in other sports.

PMID- 22582680
TI  - Effects of lavender aroma on sleep quality in healthy Japanese students.
AB  - This single-blind randomized study investigated the effectiveness of lavender
      aroma on quality of sleep in healthy Japanese students. The data of seven
      participants (2 men, 5 women) in the intervention group and eight participants (3
      men, 5 women) in the control group were analyzed (M age = 19.0 yr., SD = 0.9).
      The total procedure comprised 3 days for pre-intervention assessment, 5 days for
      the intervention, and 3 days for post-intervention assessment. Lavender exposure
      was compared with the absence of lavender (control). Information regarding the
      relaxing effect of aromas was provided to examine expectancy effects. Results
      showed that lavender aroma improved sleepiness at awakening after the
      intervention. Sex differences and daily variation in quality of sleep during the
      intervention period were not observed. The findings suggest that nighttime
      exposure to lavender aroma relieves sleepiness at awakening.

PMID- 22582681
TI  - Anticipating and training for the worst-case metabolic scenario: a comment on Del
      Vecchio, Hirata, and Franchini (2011).
AB  - Del Vecchio, Hirata, and Franchini (2011) studied the effort: pause ratio of
      mixed martial arts by analyzing 26 bouts in two separate mixed martial arts
      events in Sao Paulo, Brazil. They referenced research identifying effort:pause
      ratios from other combat sports ranging from 10:1 (Brazilian Jiu Jitsu), 2:1
      (judo and wrestling), and 1:3/1:4 (taekwondo). The authors identified an
      effort:pause ratio ranging from 1:2 to 1:4 in the bouts they analyzed, and
      suggested and described training programs that resemble this ratio. It is
      important for coaches to anticipate the most challenging metabolic mixed martial
      arts scenario and to create training programs that mimic that profile. Del
      Vecchio and associates' research is an important first step in gathering
      information which can help enhance training programs for injury prevention and
      performance enhancement.

PMID- 22582682
TI  - Sinuosity and the Affect Grid: a method for adjusting repeated mood scores.
AB  - Sinuosity is a measure of how much a travelled pathway deviates from a straight
      line. In this paper, sinuosity is applied to the measurement of mood. The Affect
      Grid is a mood scale that requires participants to place a mark on a 9 x 9 grid
      to indicate their current mood. The grid has two dimensions: pleasure-displeasure
      (horizontal) and arousal-sleepiness (vertical). In studies where repeated
      measurements are required, some participants may exaggerate their mood shifts due
      to faulty interpretation of the scale or a feeling of social obligation to the
      experimenter. A new equation is proposed, based on the sinuosity measure in
      hydrology, a measure of the meandering of rivers. The equation takes into account
      an individual's presumed tendency to exaggerate and meander to correct the score
      and reduce outliers. The usefulness of the equation is demonstrated by applying
      it to Affect Grid data from another study.

PMID- 22582683
TI  - Asymmetrical drawing patterns on the temples by left-handers.
AB  - Twenty-three Japanese genuine left-handers were selected by a Laterality Quotient
      scale and asked to draw the letter S on their own temples and foreheads. The way
      they drew on the temples showed an asymmetry that was the mirror reversal of that
      of right-handers, as found in a previous study. Left-handers drew a reversed
      letter S on their right temple much more often than on the left temple, whereas
      right-handers drew them in reverse more often on the left temple. They also drew
      it in reverse on the forehead irrespective of their handedness.

PMID- 22582684
TI  - Age, training, and previous experience predict race performance in long-distance
      inline skaters, not anthropometry.
AB  - The association of characteristics of anthropometry, training, and previous
      experience with race time in 84 recreational, long-distance, inline skaters at
      the longest inline marathon in Europe (111 km), the Inline One-eleven in
      Switzerland, was investigated to identify predictor variables for performance.
      Age, duration per training unit, and personal best time were the only three
      variables related to race time in a multiple regression, while none of the 16
      anthropometric variables were related. Anthropometric characteristics seem to be
      of no importance for a fast race time in a long-distance inline skating race in
      contrast to training volume and previous experience, when controlled with
      covariates. Improving performance in a long-distance inline skating race might be
      related to a high training volume and previous race experience. Also, doing such
      a race requires a parallel psychological effort, mental stamina, focus, and
      persistence. This may be reflected in the preparation and training for the event.
      Future studies should investigate what motivates these athletes to train and
      compete.

PMID- 22582685
TI  - Trichotomous goals of elementary school students learning English as a foreign
      language: a structural equation model.
AB  - This study applied structural equation modeling (SEM) techniques to define the
      relations among trichotomous goals (mastery goals, performance-approach goals,
      and performance-avoidance goals), self-efficacy, use of metacognitive self
      regulation strategies, positive belief in seeking help, and help-avoidance
      behavior. Elementary school students (N = 105), who were learning English as a
      foreign language, were surveyed using five self-report scales. The structural
      equation model showed that self-efficacy led to the adoption of mastery goals but
      discouraged the adoption of performance-approach goals and performance-avoidance
      goals. Furthermore, mastery goals increased the use of metacognitive self
      regulation strategies, whereas performance-approach goals and performance
      avoidance goals reduced their use. Mastery goals encouraged positive belief in
      help-seeking, but performance-avoidance goals decreased such belief. Finally,
      performance-avoidance goals directly led to help-avoidance behavior, whereas
      positive belief assumed a critical role in reducing help-avoidance. The
      established structural equation model illuminated the potential causal relations
      among these variables for the young learners in this study.

PMID- 22582686
TI  - Effect of verbal cueing on trajectory anticipation in the penalty kick among
      novice football goalkeepers.
AB  - The effect of a cueing technique on novice goalkeepers' anticipation of
      trajectory in penalty kicks was investigated. 28 novice football goalkeepers from
      junior teams were randomly selected and divided into experimental (n = 14) and
      control (n = 14) groups. Following a pre-test, participants performed 30 trials
      of a simulated penalty-kicking task in a spatially occluded condition. They were
      required to react to penalty kicks and were informed of their performance in
      anticipating the direction in which the ball was kicked. The experimental group
      received cues about the position of the non-kicking foot of the kicker, but the
      control group did not. The two-way analysis of variance showed the significant
      main effects of blocks of trials and group, but the interaction was not
      significant. The experimental group more accurately anticipated the direction of
      the penalty kicks than the control group. The cueing technique benefited the
      novice goalkeepers in anticipating the direction of penalty kicks, due to the
      informative nature of the cue for skill execution.

PMID- 22582687
TI  - Asymmetry in human cognition: further replication and extension.
AB  - Vladimir Lefebvre proposed an algebraic model of self-reflexion in the 1980s. He
      viewed reflexion as a product of the structure and computational rules of Gamma
      algebra and his equations are considered metaphors for how consciousness is
      structured. From the framework of this model, Lefebvre hypothesized an asymmetry
      in human cognition. One of the early studies supporting his model was conducted
      by Victorina Lefebvre. Over the years, other studies have been conducted, but not
      all have shown similar support as the original findings of Victorina Lefebvre.
      This study attempted to extend her findings in testing whether or not other
      ambiguous stimuli could be used in support of the model.

PMID- 22582688
TI  - Discrimination of differences in digitally manipulated phoneme length during
      speech.
AB  - The present study investigated differences in the thresholds of phoneme duration
      in word and sentence contexts by participants' sex. In the word condition, 27
      participants listened to two pairs of words in a dual pair discrimination task.
      One pair contained the same durations of /s/, and the other pair contained
      different durations of /s/. Participants were to select the pair which contained
      different durations of /s/ in the words. In the sentence condition, the other set
      of 27 participants listened to two pairs of sentences and selected the pair
      containing different durations of /s/ in the sentences. Throughout these tasks,
      the participants' just-noticeable-difference and trials-to-completion were
      analyzed. The results showed that the participants demonstrated better
      performance in detecting just-noticeable-difference in the sentence condition
      than in the word condition. In addition, a sex difference was found in just
      noticeable-difference in both conditions with better performance in men than
      women. No significant differences in trials-to-completion were found in either
      condition.

PMID- 22582689
TI  - Visual skills and playing positions of Olympic field hockey players.
AB  - Many sports require fine spatiotemporal resolution for optimal performance.
      Previous studies have compared anticipatory skills and the decision-making
      process in athletes; however, there is little information on visual skills of
      elite athletes, particularly hockey players. To assess visual skills of Olympic
      hockey players and analyze differences by playing position, and to analyze
      improvement of visual skills after training, 21 Olympic field hockey players were
      pre- and post-tested on 11 visual tasks following a 10-wk. visual training
      program consisting of computer-based visual exercises. There were no mean
      differences at pre-test between players of different positions, suggesting that
      performance on these visual skills was independent of playing position. However,
      after training, an improvement was seen in all players (when scores were averaged
      across all 11 visual tasks) with goalkeepers improving significantly more than
      any other position. This suggests the possibility of improving visual skills even
      in an elite population.

PMID- 22582690
TI  - Can the 8-coil Shakti alter subjective emotional experience? A randomized,
      placebo-controlled study.
AB  - At present, a commercially available device (the 8-coil Shakti) claims to produce
      weak and complex magnetic fields that alter neurobiological processes. The
      effects of the Shakti on emotional responses to photographs that varied on
      emotional valence were investigated. Participants (N = 37) were exposed to either
      30 min, of magnetic fields or a sham condition and rated their emotional
      reactions to a set of 54 color photographs. Although participants indicated
      significantly different emotional responses to images with distinct emotional
      valences, exposure to magnetic fields did not affect these responses, nor
      significantly interact with image emotional valence. Although the device's
      "amygdala signal" had no effect on the emotive response to images in this study,
      additional investigations examining the effects of weak and complex magnetic
      fields on various aspects of perception and cognition are warranted.

PMID- 22582691
TI  - Predicting perceived image quality: a critique of Lin and Kuo (2011).
AB  - A recent study by Lin and Kuo reported on the image quality of a small mobile
      display under different ambient illumination levels. In this commentary, the
      present author discusses the limitations of their approach with respect to the
      rigorous quantification of image quality and the caveats associated with
      preference studies of new display technologies. Quantitatively predicting image
      quality using preference-based methods can be useful for initial decisions in
      early phases of product development, but provides limited value for the rigorous
      quantification of image quality of display devices.

PMID- 22582692
TI  - Motivational orientations and task autonomy fit: effects on organizational
      attraction.
AB  - The main purpose of this study was to investigate whether there is congruence
      between applicant needs (i.e., motivational orientations) and what is available
      (i.e., task autonomy) from an organizational perspective based on the fit between
      needs and supply. The fit between work motivation and task autonomy was examined
      to see whether it was associated with organizational attraction. This
      experimental study included two phases. Phase 1 participants consisted of 446
      undergraduate students, of whom 228 were recruited to participate in Phase 2. The
      fit relations between task autonomy and intrinsic motivation and between task
      control and extrinsic motivation were characterized. Findings indicated that the
      fit between work motivation and task autonomy was positively associated with
      organizational attraction. Based on these results, it may be inferred that
      employers should emphasize job characteristics such as autonomy or control
      orientations to attract individuals, and focus on the most suitable work
      motivations for their organizations.

PMID- 22582693
TI  - Improved mental representation of space in beginner orienteers.
AB  - The purpose of the present study was to monitor any improvement in orienteering
      skills attributable to acquiring a better mental representation of space. Two
      groups were examined: the experimental group, who attended 6 mo. of orienteering
      lessons, versus the control group, who did jogging training instead. Each group,
      consisting of 20 children, was tested on the Corsi Block-tapping Test, run
      Forward and Backward, and the Star-Butterfly Test. Pre- and post-tests were
      administered. In the experimental group, scores increased in mean complexity from
      pre- to post-test on the Forward and the Backward Corsi tests, while on the Star
      Butterfly Test both time and mistakes had decreased after the training. In the
      control group, mean complexity and Star-Butterfly Test scores were unchanged from
      pre- to post-test. These results showed that after continual training in
      orienteering techniques, the orienteering group was able to remember and repeat
      sequences of events with greater precision than before the training, while these
      skills were unchanged in the control group after training in jogging.

PMID- 22582694
TI  - Age and sex differences in object control skills by children ages 5 to 14.
AB  - Object control skills provide children the tools to be physically active-a major
      societal priority. At the fundamental movement level, object control skills form
      the foundation of further sports skill development. The purpose of this study was
      to examine children's (ages 5 to 14 years, Grades K-8) development of four key
      object control skills: catching, throwing, kicking, and striking. 186 children
      were tested on selected items from the Object Control Subtest of the Test of
      Gross Motor Development-2, using a cross-sectional and correlational design. As
      anticipated, significant differences were found for age on all four skills. These
      improvements were characterized by early, rapid gains at ages 9 to 10, beyond
      which development occurred at a slower rate for catching, throwing, and kicking;
      striking development continued at a steady rate to age 14 years. Contrary to
      previous findings, no overall sex differences were found for catching or kicking.
      Overall sex differences favoring boys were observed for throwing and striking.
      Implications for evolutionary contributions to throwing and striking were
      discussed.

PMID- 22582695
TI  - Racism in soccer? Perception of challenges of black and white players by white
      referees, soccer players, and fans.
AB  - This experiment investigated challenge evaluations in soccer and their relation
      to prejudice: more precisely, whether skin colour may influence judgments of
      soccer tackles. Three groups of participants (soccer players, referees,and soccer
      fans) were asked to evaluate challenges, featuring Black and White players as
      aggressors and victims in a mixed-design study. Results showed that participants
      made some differentiations between Black and White players in a challenge
      evaluation task. Participants were more likely to consider within-group
      challenges as fouls and were faster to consider challenges made by Black players
      as fouls. On the other hand, fouls made by White players were seen as more
      severe. There were no major differences between the participating groups,
      suggesting that the observed effects were independent of how good players were or
      whether the participants were referees or not.

PMID- 22582696
TI  - Effects on modeling sequential body movements when viewed from the front or rear.
AB  - This study investigated the effect of having a model demonstration viewed from
      the rear and/or front on the subsequent acquisition of sequential gross-movement
      patterns, and further examined how participants who observed the bi-angle model
      directed their attention toward the rear view or the front view in mirror. The
      movement pattern consisted of seven pauses. A total of 36 participants was
      divided into three groups: the rear-angle group, which observed the rear view;
      the front-angle group, which observed from the front view and had to change the
      motions into their mirror opposites; and the bi-angle group, which observed the
      rear view and the front view in the mirror. The results showed that (1) all
      groups acquired the movement pattern, (2) the bi-angle and the rear-angle groups
      reproduced the demonstrated movement more accurately than the front-angle group,
      and (3) the bi-angle group tended to focus gaze on viewing the model from the
      rear. These results suggest that rear viewing was more effective than front
      viewing, because the participants could simply copy the motion, the bi-angle
      group members directed their visual attention to the view from the rear without
      any instruction about observational strategy, and modeling effect was the same
      for the rear-angle group and the bi-angle group.

PMID- 22582697
TI  - Coincident orientation of objects and viewpoint-dependence in scene recognition.
AB  - Viewpoint-dependence is a well-known phenomenon in which participants' spatial
      memory is better for previously experienced points of view than for novel ones.
      In the current study, partial-scene-recognition was used to examine the effect of
      coincident orientation of all the objects on viewpoint-dependence in spatial
      memory. When objects in scenes had no clear orientations (e.g., balls),
      participants' recognition of experienced directions was better than that of novel
      ones, indicating that there was viewpoint-dependence. However, when the objects
      in scenes were toy bears with clear orientations, the coincident orientation of
      objects (315 degrees), which was not experienced, shared the advantage of the
      experienced direction (0 degrees), and participants were equally likely to choose
      either direction when reconstructing the spatial representation in memory. These
      findings suggest that coincident orientation of objects may affect egocentric
      representations in spatial memory.

PMID- 22582698
TI  - Physical activity among postpartum adolescents: a preliminary report.
AB  - The purpose of this study was to examine the levels and correlates of physical
      activity among a sample of overweight postpartum adolescents. Postpartum
      adolescents were recruited from a university-based teen mother program and local
      school districts. Adolescents (N = 21) aged 16 to 19 years, with a child between
      6 and 12 months of age, volunteered. Participants wore a pedometer and reported
      their physical activity for seven consecutive days. Descriptive statistics and
      relationships between steps/day and self-reported physical activity, demographic,
      and psychosocial characteristics were calculated. Results indicated that
      participants were insufficiently active. Self-reported walking and pre-pregnancy
      BMI were moderately associated with steps/day. The findings of this preliminary
      study suggest that these postpartum adolescents were insufficiently active to
      attain substantial health benefits from physical activity. Postpartum adolescents
      represent an understudied population that may need to be a priority population
      for physical activity interventions.

PMID- 22582699
TI  - Sex differences in young gymnasts' postural steadiness.
AB  - The present study examined the differences between male and female gymnasts in
      bipedal standing position, back standing scale, and stork standing scale testing.
      29 young gymnasts (13 boys, 16 girls; ages 12 to 15 years) participated. A
      portable posturographic digital platform was used to record foot pressure (Foot
      Checker, Comex SA). Barefoot sole area (cm2), maximal pressure (kPa), center of
      foot pressure (CoP), sway area (mm2), and CoP linear distance displacement (mm)
      were analyzed in an integrated software module (Foot Checker, Version 4.0). The
      intra-class correlation coefficient and the coefficient of variation supported
      the reliability of the measurements. Results indicated no differences between
      boys and girls on height, weight, and Body Mass Index. Differences indicated
      better performance by girls compared to boys in back standing and stork standing.

PMID- 22582700
TI  - Measuring home advantage in Spanish handball.
AB  - Since Pollard established the system for analysing home advantage in 1986, it has
      been demonstrated and quantified in various sports, including many team sports.
      This study aims to assess whether home advantage exists in handball, using a
      sample of more than 19,000 Spanish handball league games. Results of the games
      played at home and away, the sex of the players, and the levels of the
      competition were included as variables. In Spanish handball, there was a home
      advantage of 61%, which means, on average, the team playing at home wins 61% of
      points available. This value varies according to sex and according to competition
      level, increasing as competition level decreases and season rank improves.

PMID- 22582701
TI  - Inhibitory control differentiates rare target search performance in children.
AB  - Age-related differences in rare-target search are primarily explained by the
      speed-accuracy trade-off, primed responses, or decision making. The goal was to
      examine how motor inhibition influences visual search. Children pressed a key
      when a rare target was detected. On no-target trials, children withheld
      reactions. Response time (RT), hits, misses, correct rejection, and false alarms
      were measured. Tapping tests assessed motor control. Older children tapped
      faster, were more sensitive to rare targets (higher d'), and reacted more slowly
      than younger ones. Girls outperformed boys in search sensitivity but not in RT.
      Motor speed was closely associated with hit rate and RT. Results suggest that
      development of inhibitory control plays a key role in visual detection. The
      potential implications for cognitive-motor development and individual differences
      are discussed.

PMID- 22582702
TI  - Current saturation in submicrometer graphene transistors with thin gate
      dielectric: experiment, simulation, and theory.
AB  - Recently, graphene field-effect transistors (FET) with cutoff frequencies (f(T))
      between 100 and 300 GHz have been reported; however, the devices showed very weak
      drain current saturation, leading to an undesirably high output conductance
      (g(ds)= dI(ds)/dV(ds)). A crucial figure-of-merit for analog/RF transistors is
      the intrinsic voltage gain (g(m)/g(ds)) which requires both high g(m) (primary
      component of f(T)) and low g(ds). Obtaining current saturation has become one of
      the key challenges in graphene device design. In this work, we study
      theoretically the influence of the dielectric thickness on the output
      characteristics of graphene FETs by using a surface-potential-based device model.
      We also experimentally demonstrate that by employing a very thin gate dielectric
      (equivalent oxide thickness less than 2 nm), full drain current saturation can be
      obtained for large-scale chemical vapor deposition graphene FETs with short
      channels. In addition to showing intrinsic voltage gain (as high as 34) that is
      comparable to commercial semiconductor FETs with bandgaps, we also demonstrate
      high frequency AC voltage gain and S21 power gain from s-parameter measurements.

PMID- 22582703
TI  - The MEKK1 SWIM domain is a novel substrate receptor for c-Jun ubiquitylation.
AB  - MEKK1 [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal
      regulated kinase) kinase kinase 1] is a MAP3K (MAPK kinase kinase) that regulates
      MAPK activation, and is the only known mammalian kinase that is also a ubiquitin
      ligase. MEKK1 contains a RING domain within its N-terminal regulatory region, and
      MEKK1 has been shown to ubiquitylate the AP-1 (activator protein 1) transcription
      factor protein c-Jun, but the mechanism by which MEKK1 interacts with c-Jun to
      induce ubiquitylation has not been defined. Proximal to the RING domain is a SWIM
      (SWI2/SNF2 and MuDR) domain of undetermined function. In the present study, we
      demonstrate that the MEKK1 SWIM domain, but not the RING domain, directly
      associates with the c-Jun DNA-binding domain, and that the SWIM domain is
      required for MEKK1-dependent c-Jun ubiquitylation. We further show that this
      MEKK1 SWIM-Jun interaction is specific, as SWIM domains from other proteins
      failed to bind c-Jun. We reveal that, although the Jun and Fos DNA-binding
      domains are highly conserved, the MEKK1 SWIM domain does not bind Fos. Finally,
      we identify the sequence unique to Jun proteins required for specific interaction
      with the MEKK1 SWIM domain. Therefore we propose that the MEKK1 SWIM domain
      represents a novel substrate-binding domain necessary for direct interaction
      between c-Jun and MEKK1 that promotes MEKK1-dependent c-Jun ubiquitylation.

PMID- 22582704
TI  - Angiogenesis and lymphangiogenesis in mucoepidermoid carcinoma of minor salivary
      glands.
AB  - BACKGROUND: Mucoepidermoid carcinoma is the most common malignant tumor of
      salivary glands. This tumor is characterized by a great variability in clinical
      behavior, and little is known about the pathological mechanisms involved in its
      variance. Angiogenesis is an important step in tumor progression and is believed
      to be an essential event for metastatic dissemination. METHODS: We aimed to
      investigate angiogenesis and lymphangiogenesis in mucoepidermoid carcinoma
      measuring the density of neoformed and lymphatic vessels using CD105 and D2-40
      antibodies, respectively, and by immunohistochemical evaluation of VEGF-A and
      VEGF-C proteins. It was also investigated the expression of D2-40 in neoplastic
      cells. RESULTS: We studied 26 cases of mucoepidermoid carcinoma, which showed
      great angiogenic activity measured by neoformed vessel density. However, a low
      density of lymphatics was observed. VEGF-A, VEGF-C, and D2-40 were commonly
      detected in mucoepidermoid carcinoma, but only VEGF-A expression correlated with
      neoformed vessel density. Recurrence and nodal metastasis were associated with
      low VEGF-A expression and low neoformed vessel density, indicating that impaired
      angiogenesis could lead to an aggressive phenotype. CONCLUSIONS: Angiogenesis
      seems important in the modulation of mucoepidermoid carcinoma pathogenesis;
      however, none of the parameters analyzed could predict tumor behavior.

PMID- 22582705
TI  - Electrochemical behavior of alpha1/alpha2-[Fe(H2O)P2W17O61](7-) isomers in
      solution: experimental and DFT studies.
AB  - The unusual redox behavior displayed by the two isomers of the Wells-Dawson
      phosphotungstate anion [Fe(H(2)O)P(2)W(17)O(61)](7-) is presented. The
      electrochemical measurements have been performed in aqueous media at different pH
      values from 0.5 up to 8.0. The cyclic voltammetry has also been carried out in
      organic media to get additional experimental data to establish the effect of the
      protonation on the redox properties of both isomers. At high pH values (pH >= 6)
      or in an organic medium, the reduction of the Fe center is easier in the case of
      the alpha-1 isomer, whereas for the alpha-2 isomer such reduction takes place at
      more negative potentials, as expected. In contrast, at lower pH values (pH <= 5),
      an inversion of this trend is observed, and the reduction of the Fe center
      becomes easier for the alpha-2 isomer compared to the alpha-1. We were able to
      highlight the influence of the pH and the pK(a) of the electrolyte on POM-based
      redox potentials given the pK(a) of the latter. A complementary theoretical study
      has also been performed to explain the experimental data obtained. In this sense,
      the results obtained from the DFT study are in good agreement with the
      experimental data mentioned above and have provided additional information for
      the electrochemical behavior of both isomers according to their different
      molecular orbital energies. We have also shown the influence of protonation state
      of the iron derivative on the relative reduction potentials of both isomers.

PMID- 22582706
TI  - Is robot-assisted radical cystectomy justified in the elderly? A comparison of
      robotic versus open radical cystectomy for bladder cancer in elderly >=75 years
      old.
AB  - BACKGROUND AND PURPOSE: Open radical cystectomy (ORC) or minimally invasive
      radical cystectomy with pelvic lymph node (LN) dissection carries significant
      morbidity to the elderly because they often have several medical comorbidities
      that make a surgical approach more challenging. The objective of this study is to
      compare robot-assisted radical cystectomy (RARC) and ORC in elderly patients.
      PATIENTS AND METHODS: A prospective bladder cancer cystectomy database was
      queried to identify all patients age >=75 years. A total of 20 patients were
      identified for each of the RARC and ORC cohorts. A retrospective analysis was
      performed on these 40 patients undergoing radical cystectomy for curative intent.
      RESULTS: Patients in both groups had comparable preoperative characteristics and
      demographics. Patients had significant medical comorbidities with 80% in each
      cohort having American Society of anesthesiologists classification of 3 and 50%
      having had previous abdominal surgery. Complete median operative times for RARC
      was 461 (interquartile range [IQR] 331, 554) vs 370 minutes for ORC (IQR 294,
      460) (P=0.056); however, median blood loss for RARC was 275 mL (IQR 150, 450) vs
      600 mL for ORC (IQR 500, 1925). The median hospital stay for RARC was 7 days (IQR
      5, 8) vs 14.5 days for ORC (IQR 8, 22) (P<0.001). The major complication
      (Clavien>=III) rate for RARC was 10% compared with 35% for ORC (P=0.024). There
      were two positive margins in the ORC group compared with one in the RARC group
      with median LN yields of 15 nodes (IQR 11, 22) and 17 nodes (IQR 10, 25)
      (P=0.560) respectively. CONCLUSIONS: In a comparable cohort of elderly patients,
      RARC can achieve similar perioperative outcomes without compromising pathologic
      outcomes, with less blood loss and shorter hospital stays. For an experienced
      robotic team, RARC should be considered in elderly patients because it may offer
      significant advantage with respect to perioperative morbidity over ORC.

PMID- 22582707
TI  - Pin site allergic contact dermatitis: an unusual complication of halo fixation.
AB  - We report a case of halo pin site allergic contact dermatitis, a rare
      complication of halo vest immobilisation (HVI), necessitating device removal.
      Although uncommon, pin site allergic contact dermatitis should be considered in
      patients who develop an acute dermatitis within hours to days of HVI application.

PMID- 22582708
TI  - Brassica oleracea L. Var. costata DC and Pieris brassicae L. aqueous extracts
      reduce methyl methanesulfonate-induced DNA damage in V79 hamster lung
      fibroblasts.
AB  - Brassica oleracea L. var. costata DC leaves and Pieris brassicae L. larvae
      aqueous extracts were assayed for their potential to prevent/induce DNA damage.
      None of them was mutagenic at the tested concentrations in the Ames test
      reversion assay using Salmonella His(+) TA98 strains, with and without metabolic
      activation. In the hypoxanthine-guanine phosphoribosyltransferase mutation assay
      using mammalian V79 fibroblast cell line, extracts at 500 MUg/mL neither induced
      mutations nor protected against the mutagenicity caused by methyl
      methanesulfonate (MMS). In the comet assay, none of the extracts revealed to be
      genotoxic by itself, and both afforded protection, more pronounced for larvae
      extracts, against MMS-induced genotoxicity. As genotoxic/antigenotoxic effects of
      Brassica vegetables are commonly attributed to isothiocyanates, the extracts were
      screened for these compounds by headspace-solid-phase microextraction/gas
      chromatography-mass spectrometry. No sulfur compound was detected. These findings
      demonstrate that both extracts could be useful against damage caused by genotoxic
      compounds, the larvae extract being the most promising.

PMID- 22582709
TI  - Three-dimensional metal scaffold supported bicontinuous silicon battery anodes.
AB  - Silicon-based lithium ion battery anodes are attracting significant attention
      because of silicon's exceptionally high lithium capacity. However, silicon's
      large volume change during cycling generally leads to anode pulverization unless
      the silicon is dispersed throughout a matrix in nanoparticulate form. Because
      pulverization results in a loss of electric connectivity, the reversible capacity
      of most silicon anodes dramatically decays within a few cycles. Here we report a
      three-dimensional (3D) bicontinuous silicon anode formed by depositing a layer of
      silicon on the surface of a colloidal crystal templated porous nickel metal
      scaffold, which maintains electrical connectivity during cycling due to the
      scaffold. The porous metal framework serves to both impart electrical
      conductivity to the anode and accommodate the large volume change of silicon upon
      lithiation and delithiation. The initial capacity of the bicontinuous silicon
      anode is 3568 (silicon basis) and 1450 mAh g(-1) (including the metal framework)
      at 0.05C. After 100 cycles at 0.3C, 85% of the capacity remains. Compared to a
      foil-supported silicon film, the 3D bicontinuous silicon anode exhibits
      significantly improved mechanical stability and cycleability.

PMID- 22582711
TI  - Merging constitutional and motional covalent dynamics in reversible imine
      formation and exchange processes.
AB  - The formation and exchange processes of imines of salicylaldehyde, pyridine-2
      carboxaldehyde, and benzaldehyde have been studied, showing that the former has
      features of particular interest for dynamic covalent chemistry, displaying high
      efficiency and fast rates. The monoimines formed with aliphatic alpha,omega
      diamines display an internal exchange process of self-transimination type,
      inducing a local motion of either "stepping-in-place" or "single-step" type by
      bond interchange, whose rate decreases rapidly with the distance of the terminal
      amino groups. Control of the speed of the process over a wide range may be
      achieved by substituents, solvent composition, and temperature. These monoimines
      also undergo intermolecular exchange, thus merging motional and constitutional
      covalent behavior within the same molecule. With polyamines, the monoimines
      formed execute internal motions that have been characterized by extensive one
      dimensional, two-dimensional, and EXSY proton NMR studies. In particular, with
      linear polyamines, nondirectional displacement occurs by shifting of the aldehyde
      residue along the polyamine chain serving as molecular track. Imines thus behave
      as simple prototypes of systems displaying relative motions of molecular
      moieties, a subject of high current interest in the investigation of synthetic
      and biological molecular motors. The motional processes described are of dynamic
      covalent nature and take place without change in molecular constitution. They
      thus represent a category of dynamic covalent motions, resulting from reversible
      covalent bond formation and dissociation. They extend dynamic covalent chemistry
      into the area of molecular motions. A major further step will be to achieve
      control of directionality. The results reported here for imines open wide
      perspectives, together with other chemical groups, for the implementation of such
      features in multifunctional molecules toward the design of molecular devices
      presenting a complex combination of motional and constitutional dynamic
      behaviors.

PMID- 22582710
TI  - Ragweed pollen collected along high-traffic roads shows a higher allergenicity
      than pollen sampled in vegetated areas.
AB  - BACKGROUND: Pollutants may affect pollen allergenicity and thus the prevalence of
      allergies. Although a few studies are available in literature, the connection
      between pollution and the allergenic potential of pollen has yet to be clearly
      defined. The objective of this study was to evaluate the effect of traffic
      related pollution on the allergenicity of ragweed (Ambrosia artemisiifolia L.)
      pollen through a field-based experiment. METHODS: Mature pollen grains were
      collected from ragweed plants grown along main roadsides and in vegetated areas
      of Po river plain. The percentage of sub-pollen particle-releasing grains (SPPGs)
      was evaluated immediately after sampling by microscope and image analysis.
      Immunochemistry and LC-MS/MS were applied to assess the whole allergenicity and
      the allergen pattern characterizing the different pollen samples. RESULTS: No
      statistical difference was detected in the percentage of SPPGs among pollen
      samples. Specifically, after hydration, the mean percentage was very low (<4%) in
      all the samples, regardless of the site of origin. On the contrary, pollen
      collected along high-traffic roads showed a higher whole allergenicity than
      pollen from low-traffic roads and vegetated areas which showed a reactivity
      similar to that of the commercial pollen 'Allergon', used as a standard. The
      detected higher allergenicity levels were attributed to both quantitative and
      qualitative differences in allergen pattern. CONCLUSION: Our findings show that
      pollen collected at different sites contains different amount and number of
      allergens and suggest that traffic-related pollution enhances ragweed pollen
      allergenicity, which may contribute to the increasing prevalence of ragweed
      allergy in Lombardy plain.

PMID- 22582713
TI  - Two new steroidal saponins from the biotransformation product of the rhizomes of
      Dioscorea nipponica.
AB  - Two new steroidal saponins, dioscins E (1) and F (2), along with nine known
      steroidal saponins, were isolated from the biotransformation product of the
      rhizomes of Dioscorea nipponica using Aspergillus oryzae. The structures of new
      compounds were established as 25(R)-spirost-5-en-21beta-methyl-3beta-ol-3-O-alpha
      L-rhamnopyranosyl-(1 -> 4)-beta-D-glucopyranoside (1) and (25R)-spirost-5-en
      3beta-ol-7-one 3-O-alpha-L-rhamnopyranosyl-(1 -> 4)-beta-D-glucopyranoside (2) by
      detailed spectroscopic analyses including 1D and 2D NMR spectral data ((1)H-(1)H
      COSY, HSQC, and HMBC) and MS spectrometry.

PMID- 22582714
TI  - The role of family communication in individual health attitudes and behaviors
      concerning diet and physical activity.
AB  - This study explored associations among family communication patterns
      (conversation and conformity orientations), health-specific communication
      variables, health attitudes, and health behaviors in a sample of 433 family dyads
      (N = 866). As expected, results of multilevel models revealed that individuals'
      health attitudes were strongly associated with their self-reported health
      behaviors. Findings also suggested that perceived confirmation from a family
      member during health-specific conversations (a) directly influenced health
      attitudes, (b) partially accounted for the positive relationship between family
      conversation orientation and health attitudes, and (c) partially accounted for
      the inverse relationship between family conformity orientation and health
      attitudes. Similarly, frequency of health-specific communication (a) directly
      influenced health attitudes, (b) partially accounted for the positive
      relationship between family conversation orientation and health attitudes, and
      (c) directly associated with health behaviors. Results from an actor-partner
      interdependence model (APIM) supported the aforementioned within-person
      association between a person's own health attitudes and health behaviors, as well
      as a positive relationship between young adults' health attitudes and their
      influential family member's health behaviors. Implications of these findings are
      discussed as they relate to theory and obesity prevention.

PMID- 22582712
TI  - Sexual dimorphism in rodent models of hypertension and atherosclerosis.
AB  - Approximately one third of all deaths are attributed to cardiovascular disease
      (CVD), making it the biggest killer worldwide. Despite a number of therapeutic
      options available, the burden of CVD morbidity continues to grow indicating the
      need for continued research to address this unmet need. In this respect,
      investigation of the mechanisms underlying the protection that premenopausal
      females enjoy from cardiovascular-related disease and mortality is of interest.
      In this review, we discuss the essential role that rodent animal models play in
      enabling this field of research. In particular, we focus our discussion on models
      of hypertension and atherosclerosis.

PMID- 22582715
TI  - Different mechanisms of decapitation: three classic and one unique case history.
AB  - Three classic cases and one exceptional case are reported. The unique case of
      decapitation took place in a traffic accident, while the others were seen after
      homicide, vehicle-assisted suicide, and after long-jump hanging. Thorough scene
      examinations were performed, and photographs from the scene were available in all
      cases. Through the autopsy of each case, the mechanism for the decapitation in
      each case was revealed. The severance lines were through the neck and the
      cervical vertebral column, except for in the motor vehicle accident case, where
      the base of skull was fractured. This case was also unusual as the mechanism was
      blunt force. In the homicide case, the mechanism was the use of a knife combined
      with a saw, while in the two last cases, a ligature made the cut through the
      neck. The different mechanisms in these decapitations are suggested.

PMID- 22582718
TI  - Transfer, attachment, and formation of biofilms by Escherichia coli O157:H7 on
      meat-contact surface materials.
AB  - Studies examined the effects of meat-contact material types, inoculation
      substrate, presence of air at the liquid-solid surface interface during
      incubation, and incubation substrate on the attachment/transfer and subsequent
      biofilm formation by Escherichia coli O157:H7 on beef carcass fabrication surface
      materials. Materials studied as 2 * 5 cm coupons included stainless steel,
      acetal, polypropylene, and high-density polyethylene. A 6-strain rifampicin
      resistant E. coli O157:H7 composite was used to inoculate (6 log CFU/mL, g, or
      cm2) tryptic soy broth (TSB), beef fat/lean tissue homogenate (FLH), conveyor
      belt-runoff fluids, ground beef, or beef fat. Coupons of each material were
      submerged (4  degrees C, 30 min) in the inoculated fluids or ground beef, or
      placed between 2 pieces of inoculated beef fat with pressure (20 kg) applied.
      Attachment/transfer of the pathogen was surface material and substrate dependent,
      although beef fat appeared to negate differences among surface materials. Beef
      fat was the most effective (P < 0.05) inoculation substrate, followed by ground
      beef, FLH, and TSB. Incubation (15  degrees C, 16 d) of beef fat-inoculated
      coupons in a beef fat homogenate (pH 4.21) allowed the pathogen to survive and
      grow on coupon surfaces, with maximal biofilm formation observed between 2 and 8
      d of storage and when air was present at the liquid-solid interface. The results
      indicated that the process of fabricating beef carcasses may be conducive to the
      attachment of E. coli O157:H7 onto meat-contact surfaces and subsequent biofilm
      formation. Furthermore, it is recommended that substrates found in beef
      fabrication settings, rather than laboratory culture media, be used in studies
      designed to investigate E. coli O157:H7 biofilm development and control in these
      environments. PRACTICAL APPLICATION: Findings of this study provide knowledge on
      the effect of type of beef carcass fabrication surface material, fabrication
      floor fluids and residues, and incubation conditions on attachment/transfer and
      subsequent biofilm formation by E. coli O157:H7. The results highlight the
      importance of thoroughly cleaning soiled surfaces to remove all remnants of beef
      fat or other organic material that may harbor or protect microbial contaminants
      during otherwise lethal antimicrobial interventions.

PMID- 22582719
TI  - Serious gastric ulcer event after stereotactic body radiotherapy (SBRT) delivered
      with concomitant vinorelbine in a patient with left adrenal metastasis of lung
      cancer.

PMID- 22582720
TI  - Assessing coronary disease in symptomatic women by the Morise score.
AB  - BACKGROUND: Early identification of coronary artery disease (CAD) among
      symptomatic women is critical given their worse outcomes as compared to men. We
      evaluated the value of the Morise score, a simple clinical risk score, for the
      assessment for CAD as determined by computed tomography coronary angiography
      (CTCA) and compared it to the Diamond-Forrester risk assessment. METHODS: One
      hundred forty women (mean age, 64+/-11 years) with chest pain syndromes and no
      known CAD referred for CTCA were analyzed. Patients were risk stratified for
      likelihood of CAD by Morise and Diamond-Forrester scores. The presence and degree
      of CAD were determined by CTCA and classified as normal, nonobstructive (<50%
      stenosis), or obstructive (>50% stenosis). Total coronary calcium was calculated
      based on Agatston scores. RESULTS: When risk was assessed by Morise vs. Diamond
      Forrester, 5% vs. 7% of women were stratified as low, 41% vs. 82% as
      intermediate, and 54% vs. 11% as high risk for CAD, respectively. CAD was present
      in 95 (68%) patients; 22 (16%) had obstructive CAD, and 73 (52%) had
      nonobstructive CAD. Morise scores significantly correlated with calcium scores
      (p<0.001) as well as the presence and degree of CAD (p<0.0001). Morise scores
      also demonstrated significantly higher accuracy (66% vs. 48%, p<0.005) and higher
      sensitivity (56% vs. 16%, p<0.001) but lower specificity (82% vs. 97%, p<0.05)
      when compared to Diamond-Forrester risk assessment. CONCLUSIONS: The Morise score
      performed better than Diamond-Forrester for CAD risk assessment, which highlights
      the importance and power of a simple history and physical examination in
      determining women at risk for CAD.

PMID- 22582721
TI  - Spontaneous preterm labor and cardiovascular disease risk: one step closer to a
      better understanding.

PMID- 22582722
TI  - Genome-wide association study of insect bite hypersensitivity in Dutch Shetland
      pony mares.
AB  - Insect bite hypersensitivity (IBH) is the most common allergic disease present in
      horses worldwide. It has been shown that IBH is under genetic control, but the
      knowledge of associated genes is limited. We conducted a genome-wide association
      study to identify and quantify genomic regions contributing to IBH in the Dutch
      Shetland pony population. A total of 97 cases and 91 controls were selected and
      matched on withers height, coat colour and pedigree to minimise the population
      stratification. A blood sample was collected from participating Shetland pony
      mares, their IBH phenotype was scored and the owner filled in a questionnaire. A
      total of 40 021 single-nucleotide polymorphisms (SNPs) were fitted in a
      univariable logistic model fitting an additive effect. Analysis revealed no
      effects of population stratification. Significant associations with IBH were
      detected for 24 SNPs on 12 chromosomes [-log(10) (P-value) > 2.5]. Odds ratios of
      allele substitution effects of the unfavourable allele were between 1.94 and
      5.95. The most significant SNP was found on chromosome 27, with an odds ratio of
      2.31 and with an allele frequency of the unfavourable allele of 0.72 in cases and
      0.53 in controls. Genome-wide association studies on additional horse populations
      are desired to validate the identified associations, to identify the genes
      involved in IBH and to develop genomic tools to decrease IBH prevalence.

PMID- 22582723
TI  - Siansivirga zeaxanthinifaciens gen. nov., sp. nov., a novel zeaxanthin-producing
      member of the family Flavobacteriaceae isolated from coastal seawater of Taiwan.
AB  - A strictly aerobic, Gram-negative, rod-shaped bacterium (strain CC-SAMT-1(T))
      showing gliding motility was isolated from coastal seawater of China Sea, Taiwan.
      Strain CC-SAMT-1(T) synthesizes all-trans-zeaxanthin (6.5 +/- 0.5 mg g(-1) dry
      biomass) as a predominant xanthophyll carotenoid. As determined by 16S rRNA gene
      analysis, strain CC-SAMT-1(T) shared very high sequence similarity to the members
      of the genera Mariniflexile (96.1-95.3%) and Gaetbulibacter (96.0-95.9%);
      however, it formed a distinct phyletic lineage distantly associated with
      Mariniflexile species. Polar lipid profile constitutes phosphatidylethanolamine,
      four unidentified aminolipids, four unidentified lipids, and an unidentified
      glycolipid. Strain CC-SAMT-1(T) contains excessive unidentified aminolipid lipid
      (AL2-4) and glycolipid contents, and therefore clearly distinct from
      Mariniflexile species. Major fatty acids (> 5% of total fatty acids) were iso
      C(15:0) (14.8%), iso-C(17:0) 3-OH (11.8%), iso-C(15:1) G (10.6%), anteiso-C(15:0)
      (9.7%), C(16:0) (8.1%), iso-C(16:0) 3-OH (7.9%), iso-C(15:0) 3-OH (7.5%), and
      summed feature 3 (containing C(16:1) omega6c and/or C(16:1) omega7c) (7.5%).
      Menaquinone-6 (MK-6) was major respiratory quinone. DNA G+C content was 33.7
      mol%. Based on polyphasic taxonomy, strain CC-SAMT-1(T) represents a novel genus
      and species in the family Flavobacteriaceae for which the name Siansivirga
      zeaxanthinifaciens gen. nov., sp. nov. is proposed. The type strain is CC-SAMT
      1(T) (= BCRC 80315(T) = JCM 17682(T)).

PMID- 22582725
TI  - When customers exhibit verbal aggression, employees pay cognitive costs.
AB  - In 4 experimental studies, we show that customer verbal aggression impaired the
      cognitive performance of the targets of this aggression. In Study 1, customers'
      verbal aggression reduced recall of customers' requests. Study 2 extended these
      findings by showing that customer verbal aggression impaired recognition memory
      and working memory among employees of a cellular communication provider. In Study
      3, the ability to take another's perspective attenuated the negative effects of
      customer verbal aggression on participants' cognitive performance. Study 4 linked
      customer verbal aggression to quality of task performance, showing a particularly
      negative influence of aggressive requests delivered by high-status customers.
      Together, these studies suggest that the effects of even minor aggression from
      customers can strongly affect the immediate cognitive performance of customer
      service employees and reduce their task performance. The implications for
      research on aggression and for the practice of customer service are discussed.

PMID- 22582726
TI  - Understanding and estimating the power to detect cross-level interaction effects
      in multilevel modeling.
AB  - Cross-level interaction effects lie at the heart of multilevel contingency and
      interactionism theories. Researchers have often lamented the difficulty of
      finding hypothesized cross-level interactions, and to date there has been no
      means by which the statistical power of such tests can be evaluated. We develop
      such a method and report results of a large-scale simulation study, verify its
      accuracy, and provide evidence regarding the relative importance of factors that
      affect the power to detect cross-level interactions. Our results indicate that
      the statistical power to detect cross-level interactions is determined primarily
      by the magnitude of the cross-level interaction, the standard deviation of lower
      level slopes, and the lower and upper level sample sizes. We provide a Monte
      Carlo tool that enables researchers to a priori design more efficient multilevel
      studies and provides a means by which they can better interpret potential
      explanations for nonsignificant results. We conclude with recommendations for how
      scholars might design future multilevel studies that will lead to more accurate
      inferences regarding the presence of cross-level interactions.

PMID- 22582727
TI  - Test publishers' perspective on "an updated meta-analysis": comment on Van
      Iddekinge, Roth, Raymark, and Odle-Dusseau (2012).
AB  - Van Iddekinge, Roth, Raymark, and Odle-Dusseau's (2012) meta-analysis of pre
      employment integrity test results confirmed that such tests are meaningfully
      related to counterproductive work behavior. The article also offered some
      cautionary conclusions, which appear to stem from the limited scope of the
      authors' focus and the specific research procedures used. Issues discussed in
      this commentary include the following: (a) test publishers' provision of studies
      for meta-analytic consideration; (b) errors and questions in the coding of
      statistics from past studies; (c) debatable corrections for unreliable criterion
      measures; (d) exclusion of laboratory, contrasted-groups, unit-level, and time
      series studies of counterproductive behavior; (e) under-emphasis on the
      prediction of counterproductive workplace behaviors compared with job
      performance, training outcomes, and turnover; (f) overlooking the industry
      practice of deploying integrity scales with other valid predictors of employee
      outcomes; (g) implication that integrity test publishers produce biased research
      results; (h) incomplete presentation of integrity tests' resistance to faking;
      and (i) omission of data indicating applicants' favorable response to integrity
      tests, the tests' lack of adverse impact, and the positive business impact of
      integrity testing. This commentary, therefore, offers an alternate perspective,
      addresses omissions and apparent inaccuracies, and urges a return to the use of
      diverse methodologies to evaluate the validity of integrity tests and other
      psychometric instruments.

PMID- 22582728
TI  - Integrity tests predict counterproductive work behaviors and job performance
      well: comment on Van Iddekinge, Roth, Raymark, and Odle-Dusseau (2012).
AB  - Examination of the Van Iddekinge, Roth, Raymark, and Odle-Dusseau (2012) meta
      analysis reveals a number of problems. They meta-analyzed a partial database of
      integrity test validities. An examination of their coded database revealed that
      measures coded as integrity tests and meta-analyzed as such often included scales
      that are not in fact integrity tests. In addition, there were important
      deficiencies in their analytic approach relating to application of range
      restriction corrections and identification of moderators. We found the absence of
      fully hierarchical moderator analyses to be a serious weakness. We also explain
      why empirical comparisons between test publishers versus non-publishers cannot
      unambiguously lead to inferences of bias, as alternate explanations are possible,
      even likely. In light of the problems identified, it appears that the conclusions
      about integrity test validity drawn by Van Iddekinge et al. cannot be considered
      accurate or reliable.

PMID- 22582729
TI  - The critical role of the research question, inclusion criteria, and transparency
      in meta-analyses of integrity test research: a reply to Harris et al. (2012) and
      Ones, Viswesvaran, and Schmidt (2012).
AB  - We clear up a number of misconceptions from the critiques of our meta-analysis
      (Van Iddekinge, Roth, Raymark, & Odle-Dusseau, 2012). We reiterate that our
      research question focused on the criterion-related validity of integrity tests
      for predicting individual work behavior and that our inclusion criteria flowed
      from this question. We also reviewed the primary studies we could access from
      Ones, Viswesvaran, and Schmidt's (1993) meta-analysis of integrity tests and
      found that only about 30% of the studies met our inclusion criteria. Further,
      analyses of some of the types of studies we had to exclude revealed potentially
      inflated validity estimates (e.g., corrected validities as high as .80 for
      polygraph studies). We also discuss our experience trying to obtain primary
      studies and other information from authors of Harris et al. (2012) and Ones,
      Viswesvaran, and Schmidt (2012). In addition, we address concerns raised about
      certain decisions we made and values we used, and we demonstrate how such
      concerns would have little or no effect on our results or conclusions. Finally,
      we discuss some other misconceptions about our meta-analysis, as well as some
      divergent views about the integrity test literature in general. Overall, we stand
      by our research question, methods, and results, which suggest that the validity
      of integrity tests for criteria such as job performance and counterproductive
      work behavior is weaker than the authors of the critiques appear to believe.

PMID- 22582730
TI  - On reconciling conflicting meta-analytic findings regarding integrity test
      validity.
AB  - We react to the Van Iddekinge, Roth, Raymark, and Odle-Dusseau (2012a) meta
      analysis of the relationship between integrity test scores and work-related
      criteria, the earlier Ones, Viswesvaran, and Schmidt (1993) meta-analysis of
      those relationships, the Harris et al. (2012) and Ones, Viswesvaran, and Schmidt
      (2012) responses, and the Van Iddekinge, Roth, Raymark, and Odle-Dusseau (2012b)
      rebuttal. We highlight differences between the findings of the 2 meta-analyses by
      focusing on studies that used predictive designs, applicant samples, and non-self
      report criteria. We conclude that study exclusion criteria, correction for
      artifacts, and second order sampling error are not likely explanations for the
      differences in findings. The lack of detailed documentation of all effect size
      estimates used in either meta-analysis makes it impossible to ascertain the bases
      for the differences in findings. We call for increased detail in meta-analytic
      reporting and for better information sharing among the parties producing and meta
      analytically integrating validity evidence.

PMID- 22582732
TI  - Cognitive functioning and age at onset in non-affective psychotic disorder.
AB  - OBJECTIVE: Age at psychosis onset has been related to variability in cognitive
      functioning, but its effect may be mediated by demographic and clinical factors.
      The aim of the current study was to study the contribution of age at onset, as
      well as demographic and illness characteristics, to variation in cognitive
      functioning in patients with schizophrenia spectrum disorder. METHOD: Patients (n
      = 1053) and healthy controls (n = 631) underwent comprehensive neuropsychological
      and clinical assessments. The effect of age at onset on age-standardized
      cognitive test scores was assessed with multiple linear regression analyses.
      Mediation by illness and demographic factors was tested using a multiple
      mediation Sobel test. RESULTS: A diagnosis of schizophrenia, higher antipsychotic
      dose, and more negative symptoms were associated with earlier onset of illness,
      while female sex and a more chronic course were associated with later illness
      onset. Furthermore, earlier onset was associated with worse performance on
      immediate recall and sustained attention. However, male sex, more negative
      symptoms, and higher antipsychotic dose mediated the effect of age at onset on
      memory, while negative symptoms explained its association with
      attention/vigilance. CONCLUSION: Greater impairment in memory and attention in
      early-onset psychosis may be explained by features indicative of underlying
      neurodevelopmental vulnerability.

PMID- 22582734
TI  - Genes expression profiling of peripheral blood cells of patients with
      hepatocellular carcinoma.
AB  - HCC (hepatocellular carcinoma) is often diagnosed at an advanced stage with poor
      prognosis. Peripheral blood may be useful in cancer classification, and therefore
      we investigated the gene expression found by Affymetrix HG-U133 Plus2.0
      microarray, with samples from nine HCC patients and five healthy NC (normal
      controls). A total of 726 probe sets showed significant differences based on the
      criteria of P<0.05 and absolute fold change >2. The genes were related to many
      biological functions, including immune response, transcription regulation and
      metabolism processes. Ten genes [IL-8 (interleukin 8), GOS2 (G0 /G1 switch gene
      2), CXCR4 (CXC chemokine receptor 4), FOS, RPS24 (40S ribosomal protein S24),
      HAP90AA1, PFDN5, RPL27, GZMA and PFN1] showing significant differences were
      confirmed by real-time PCR in 54 HCC patients and 56 healthy NC. Seven genes [IL
      8, GOS2, CXCR4, FOS, RPS24, HSP90AA1 (heat shock protein 90AA1) and PFN1] showed
      significant difference both in RT-PCR (reverse transcription-PCR) and microarray.
      Expression of IL-8 and FOS proteins was up-regulated in HCC compared with healthy
      controls. A gene signature in peripheral blood which can distinguish HCC patients
      and healthy controls may have been identified. 

PMID- 22582735
TI  - Different levels of testicular organization during gonadal differentiation in
      B6.Y(Tir) mice manifesting sex reversal.
AB  - B6.Y(Tir) (mice with Y chromosome from a strain in Tirano, Italy, and autosomes
      and X-chromosomes from the B6 strain) mice provide an excellent model for
      analysing sex development that occurs during gonadal differentiation; however,
      the molecular mechanisms that contribute to sex reversal are unclear. Our aim has
      been to establish which molecular events participate in this sex reversal. The
      pattern of gene expression related to testicular [Sry (sex-determining region of
      the Y chromosome), Sox9 (Sry-related high-mobility group box gene 9) and Mis
      (Mullerian-inhibiting substance)] and ovarian [Wnt4 (Wingless-type MMTV (murine
      mammary-tumour virus) integration site family, member 4), Rspo1 (cysteine-rich
      secretory protein containing a thrombospondin type 1 repeat) and Stra8
      (stimulated by retinoic acid gene 8)] differentiation was analysed by applying
      immunofluorescence and real-time RT-PCR (reverse transcription-PCR), focusing on
      XY gonads from the B6.Y(Tir) mouse, but also analysing the normal strains CD-1
      and C57BL/6J (B6). The expression of genes related to the process of sexual
      differentiation was altered in the case of the B6.Y(Tir) strain, both at the
      transcript and protein level, inducing differentiation of ovaries and ovotestes,
      but not the formation of the testes, which were normal. Our results indicate that
      the expression of testicular genes is inhibited at various levels, permitting the
      expression of ovarian genes such as Wnt4, Stra8 and Rspo1. However, their
      activity was not clear when the data were averaged. Correlation analysis
      indicated that an ovary differentiation pathway is activated when the testicular
      differentiation pathway is inhibited. 

PMID- 22582736
TI  - Studies on the relative reactivity of three hydroxyl groups in aconitine.
AB  - The relative reactivity of three hydroxyl groups in aconitine toward acetylation,
      chlorination, sulfonylation, and oxidation has been studied in this paper. The
      reduction of C-3 ketone and C-15 ketone derivatives of aconitine was also
      investigated. It was found that (1) the relative reactivity of three hydroxyl
      groups toward acetylation, chlorination, and sulfonylation is 3-OH>13-OH>>15-OH;
      (2) 3-OH is much more reactive than 15-OH toward oxidation; and (3) reduction of
      the carbonyl group at C-3 with NaBH(4) generated a pair of C-3 epimers, while the
      reduction products of the carbonyl group at C-15 depend largely on the specific
      reducing agent and the absolute configuration of 16-OCH(3). When the substrate
      has 16beta-OCH(3), its carbonyl group at C-15 can be reduced with NaBH(4) to
      yield exclusively the 15alpha-OH-containing product. Upon replacement of reducing
      agent NaBH(4) with LiAlH(4), the C-15 carbonyl group can be reduced to yield a
      pair of C-15 epimers. On the other hand, when the substrate has 16alpha-OCH(3), C
      15 carbonyl group can only be reduced to generate 15alpha-OH-containing product.

PMID- 22582733
TI  - Regulation of synaptic functions in central nervous system by endocrine hormones
      and the maintenance of energy homoeostasis.
AB  - Energy homoeostasis, a co-ordinated balance of food intake and energy
      expenditure, is regulated by the CNS (central nervous system). The past decade
      has witnessed significant advances in our understanding of metabolic processes
      and brain circuitry which responds to a broad range of neural, nutrient and
      hormonal signals. Accumulating evidence demonstrates altered synaptic plasticity
      in the CNS in response to hormone signals. Moreover, emerging observations
      suggest that synaptic plasticity underlies all brain functions, including the
      physiological regulation of energy homoeostasis, and that impaired synaptic
      constellation and plasticity may lead to pathological development and conditions.
      Here, we summarize the current knowledge on the regulation of postsynaptic
      receptors such as AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic
      acid), NMDA (N-methyl-D-aspartate) and GABA (gamma-aminobutyric acid) receptors,
      and the presynaptic components by hormone signals. A detailed understanding of
      the neurobiological mechanisms by which hormones regulate energy homoeostasis may
      lead to novel strategies in treating metabolic disorders.

PMID- 22582737
TI  - Dealing with feeling: a meta-analysis of the effectiveness of strategies derived
      from the process model of emotion regulation.
AB  - The present meta-analysis investigated the effectiveness of strategies derived
      from the process model of emotion regulation in modifying emotional outcomes as
      indexed by experiential, behavioral, and physiological measures. A systematic
      search of the literature identified 306 experimental comparisons of different
      emotion regulation (ER) strategies. ER instructions were coded according to a new
      taxonomy, and meta-analysis was used to evaluate the effectiveness of each
      strategy across studies. The findings revealed differences in effectiveness
      between ER processes: Attentional deployment had no effect on emotional outcomes
      (d(+) = 0.00), response modulation had a small effect (d(+) = 0.16), and
      cognitive change had a small-to-medium effect (d(+) = 0.36). There were also
      important within-process differences. We identified 7 types of attentional
      deployment, 4 types of cognitive change, and 4 types of response modulation, and
      these distinctions had a substantial influence on effectiveness. Whereas
      distraction was an effective way to regulate emotions (d(+) = 0.27),
      concentration was not (d(+) = -0.26). Similarly, suppressing the expression of
      emotion proved effective (d(+) = 0.32), but suppressing the experience of emotion
      or suppressing thoughts of the emotion-eliciting event did not (d(+) = -0.04 and 
      0.12, respectively). Finally, reappraising the emotional response proved less
      effective (d(+) = 0.23) than reappraising the emotional stimulus (d(+) = 0.36) or
      using perspective taking (d(+) = 0.45). The review also identified several
      moderators of strategy effectiveness including factors related to the (a) to-be
      regulated emotion, (b) frequency of use and intended purpose of the ER strategy,
      (c) study design, and (d) study characteristics.

PMID- 22582738
TI  - The psychological effects of meditation: a meta-analysis.
AB  - In this meta-analysis, we give a comprehensive overview of the effects of
      meditation on psychological variables that can be extracted from empirical
      studies, concentrating on the effects of meditation on nonclinical groups of
      adult meditators. Mostly because of methodological problems, almost 3/4 of an
      initially identified 595 studies had to be excluded. Most studies appear to have
      been conducted without sufficient theoretical background. To put the results into
      perspective, we briefly summarize the major theoretical approaches from both East
      and West. The 163 studies that allowed the calculation of effect sizes exhibited
      medium average effects (r = .28 for all studies and r = .27 for the n = 125
      studies from reviewed journals), which cannot be explained by mere relaxation or
      cognitive restructuring effects. In general, results were strongest (medium to
      large) for changes in emotionality and relationship issues, less strong (about
      medium) for measures of attention, and weakest (small to medium) for more
      cognitive measures. However, specific findings varied across different approaches
      to meditation (transcendental meditation, mindfulness meditation, and other
      meditation techniques). Surprisingly, meditation experience only partially
      covaried with long-term impact on the variables examined. In general, the
      dependent variables used cover only some of the content areas about which
      predictions can be made from already existing theories about meditation; still,
      such predictions lack precision at present. We conclude that to arrive at a
      comprehensive understanding of why and how meditation works, emphasis should be
      placed on the development of more precise theories and measurement devices.

PMID- 22582740
TI  - A medical profession in transition: exploring naturopathic physician blogging
      behaviors.
AB  - Naturopathic medicine is a holistic healing approach involving natural remedies,
      wellness, and disease prevention. A literature review shows the discipline is
      attempting to overcome several professional obstacles and expand into new areas.
      Amid this transition, the naturopathic community--like other groups--has adopted
      Web 2.0 technologies such as blogs. This article features interviews with one
      naturopathic medical student and 17 naturopathic physicians and reviews of
      interviewee blogs to understand this group's communication activities. Findings
      suggest blogs are venues for projecting both individual and group credibility to
      stakeholders. I conclude that blogs serve a "represent all of us" group function
      and are new examples of gray or alternative health literature.

PMID- 22582739
TI  - Reconstructing constructivism: causal models, Bayesian learning mechanisms, and
      the theory theory.
AB  - We propose a new version of the "theory theory" grounded in the computational
      framework of probabilistic causal models and Bayesian learning. Probabilistic
      models allow a constructivist but rigorous and detailed approach to cognitive
      development. They also explain the learning of both more specific causal
      hypotheses and more abstract framework theories. We outline the new theoretical
      ideas, explain the computational framework in an intuitive and nontechnical way,
      and review an extensive but relatively recent body of empirical results that
      supports these ideas. These include new studies of the mechanisms of learning.
      Children infer causal structure from statistical information, through their own
      actions on the world and through observations of the actions of others. Studies
      demonstrate these learning mechanisms in children from 16 months to 4 years old
      and include research on causal statistical learning, informal experimentation
      through play, and imitation and informal pedagogy. They also include studies of
      the variability and progressive character of intuitive theory change,
      particularly theory of mind. These studies investigate both the physical and the
      psychological and social domains. We conclude with suggestions for further
      collaborative projects between developmental and computational cognitive
      scientists.

PMID- 22582741
TI  - Interspinous distractor devices for the management of lumbar spinal stenosis: a
      miracle cure for a common problem?
AB  - Neurogenic claudication due to lumbar spinal stenosis is the commonest cause of
      back and leg pain in the elderly. It consumes large amounts of healthcare
      resource and is a common reason for GP consultations. Surgical management by
      decompressive laminectomy is the traditional method used for those patients in
      whom conservative management has failed. However, the advent of minimally
      invasive interspinous distraction devices, which are designed to alleviate
      symptoms of neurogenic intermittent claudication without subjecting the patient
      to a major operation, has potentially revolutionised the management of lumbar
      spinal stenosis. This review describes the principles of interspinous distraction
      devices, the rationale for their use in the management of lumbar spinal stenosis,
      indications and predictors of outcome. Published data on the safety and efficacy
      of the various devices available is encouraging but long term results are
      awaited. The superiority of interspinous distraction devices over conservative
      treatment has already been established, however, the precise indication for this
      new technology and whether the implants can replace conventional decompressive
      surgery in some situations has not been clearly defined.

PMID- 22582742
TI  - Preparation and nuclear magnetic resonance spectra of hydridophosphine complexes
      of ruthenium and rhodium.

PMID- 22582743
TI  - Transport properties of a single-molecule diode.
AB  - Charge transport through single diblock dipyrimidinyl diphenyl molecules
      consisting of a donor and acceptor moiety was measured in the low-bias regime and
      as a function of bias at different temperatures using the mechanically
      controllable break-junction technique. Conductance histograms acquired at 10 mV
      reveal two distinct peaks, separated by a factor of 1.5, representing the two
      orientations of the single molecule with respect to the applied bias. The current
      voltage characteristics exhibit a temperature-independent rectification of up to
      a factor of 10 in the temperature range between 300 and 50 K with single-molecule
      currents of 45-70 nA at +/-1.5 V. The current-voltage characteristics are
      discussed using a semiempirical model assuming a variable coupling of the
      molecular energy levels as well as a nonsymmetric voltage drop across the
      molecular junction, thus shifting the energy levels accordingly. The excellent
      agreement of the data with the proposed model suggests that the rectification
      originates from an asymmetric Coulomb blockade in combination with an electric
      field-induced level shifting.

PMID- 22582744
TI  - Self-renewal and multipotency coexist in a long-term cultured adult rat dental
      pulp stem cell line: an exception to the rule?
AB  - The stemness state is characterized by self-renewal and differentiation
      properties. However, stem cells are not able to preserve these characteristics in
      long-term culture because of the intrinsic fragility of their phenotype easily
      undergoing senescence or neoplastic transformation. Furthermore, although
      isolated from the same original tissue using similar protocols, adult stem cells
      can display dissimilar phenotypes and important cell clone/species contamination.
      Finally, the lack of a clear standardization contributes to complicate the
      comprehension about the stemness condition. In this context, cell lines
      displaying a particularly stable phenotype must be identified to define one or
      multiple benchmarks against which other stem cell lines could be reliably
      assessed. The present paper demonstrates that it is possible to isolate from the
      rat dental pulp a stem cell line (MUR-1) that does not display neoplastic
      transformation in long-term culture. MUR-1 cells stably express a broad range of
      stemness markers and are able to differentiate into adipogenic, osteogenic,
      chondrogenic, neurogenic, and cardiomyogenic lineages independently of the
      culture passages. Moreover, serial in vitro passages have not changed their
      immunophenotype, proliferation capacity, or differentiation potential. The
      uniqueness of these characteristics candidates MUR-1 as a model to reliably
      improve the understanding of the mechanisms governing the stem cell fate in the
      same as well as in other stem cell populations.

PMID- 22582746
TI  - Radical mechanism in the elimination of 2-arylsulfinyl esters.
AB  - The mechanism of the dehydrosulfenylation of 2-arylsulfinyl esters was
      investigated. The reaction was found to follow a homolytic cleavage mechanism as
      verified by electrospray ionization tandem mass spectrometry and experimental
      work. Rearranged sulfoxides are obtained as byproduct during the elimination
      reaction.

PMID- 22582745
TI  - Clinimetrics of measures of oropharyngeal dysphagia for preschool children with
      cerebral palsy and neurodevelopmental disabilities: a systematic review.
AB  - AIM: The aim of this study was to determine the psychometric properties and
      clinical utility of objective measures of oropharyngeal dysphagia (OPD) in
      children with cerebral palsy or neurodevelopmental disabilities aged 12 months to
      5 years. METHOD: Five electronic databases were searched to identify measures of
      OPD. The Consensus-based Standards for the Selection of Measurement Instruments
      (COSMIN) Checklist was used to assess psychometric properties and a Modified
      CanChild Outcome Rating Form was used for clinical utility. RESULTS: Nine
      measures of OPD from 27 papers were assessed: the Brief Assessment of Motor
      Function - Oral Motor Deglutition Scale; the Behavioral Assessment Scale of Oral
      Functions in Feeding; the Dysphagia Disorders Survey; the Feeding Behaviour
      Scale; the Functional Feeding Assessment, modified; the Gisel Video Assessment;
      the Oral Motor Assessment Scale; the Pre-Speech Assessment Scale; and the
      Schedule for Oral Motor Assessment. INTERPRETATION: The Schedule for Oral Motor
      Assessment and the Functional Feeding Assessment, modified, proved to be the
      strongest measures based on published psychometric properties of validity and
      reliability. The Schedule for Oral Motor Assessment and the Dysphagia Disorders
      Survey were found to have the strongest clinical utility. Further studies to test
      the psychometric properties of existing measures, in particular predictive
      validity, responsiveness, and test-retest reliability, would be beneficial for
      selecting an appropriate measure for both clinical and research contexts.

PMID- 22582747
TI  - Reliability and validity of the Chinese version of the chronic oral mucosal
      diseases questionnaire.
AB  - INTRODUCTION: The aim of this study was to evaluate the reliability and validity
      of the Chinese version of the Chronic Oral Mucosal Diseases Questionnaire
      (COMDQ). METHODS: A consecutive sample of 200 patients with chronic oral mucosal
      diseases was enrolled to complete the questionnaire after its translation and
      cross-cultural adaptation. The reliability of the Chinese version of COMDQ was
      determined through internal consistency and test-retest methods. The construct
      validity of COMDQ was analysed by exploratory factor analysis (EFA). RESULTS:
      Cronbach's alpha value for the total COMDQ score was 0.894, and the test-retest
      intraclass correlation coefficient value for the total COMDQ score was 0.83. The
      EFA extracted four factors, which accounted for 67.89% of the variance. All items
      showed adequate factor loadings, ranging from 0.487 to 0.947. CONCLUSION: The
      results suggest that the Chinese version of the COMDQ has satisfactory
      psychometric properties and is applicable to patients with chronic oral mucosal
      diseases in China.

PMID- 22582748
TI  - Polydactyly mutation is linked with chromosome 2p region in Beijing fatty
      chicken.

PMID- 22582749
TI  - Experimental arthritis exacerbates Aggregatibacter actinomycetemcomitans-induced
      periodontitis in mice.
AB  - AIM: This study aimed to investigate whether chronic antigen-induced arthritis
      (AIA) influences infection-induced periodontitis (PD) in mice and whether PD
      modifies the clinical course of AIA. The contribution of anti-TNF-alpha therapy
      was also evaluated. MATERIALS AND METHODS: The PD was induced in C57BL/6 mice by
      oral infection with Aggregatibacter actinomycetemcomitans. AIA was induced after
      infection. Anti-TNF-alpha and chlorhexidine therapies were used to investigate
      the role of TNF-alpha and oral infection on PD and AIA interaction. Maxillae,
      knee joints, lymph nodes and serum samples were used for histomorphometric,
      immunoenzymatic and/or real time-PCR analyses. RESULTS: Antigen-induced arthritis
      exacerbated alveolar bone loss triggered by PD infection. In contrast, PD did not
      influence AIA in the evaluated time-points. PD exacerbation was associated with
      enhanced production of IFN-gamma in maxillae and expression of the Th1
      transcription factor tBET in submandibular lymph nodes. Increased serum levels of
      IL-6 and C-reactive protein were also detected. Anti-TNF-alpha and antiseptic
      therapies prevented the development and exacerbation of infectious-PD. Anti-TNF
      alpha therapy also resulted in reduced expression of IFN-gamma, TNF-alpha and IL
      17 in maxillae. CONCLUSIONS: Altogether, the current results indicate that the
      exacerbation of infection-induced PD by arthritis is associated with an
      alteration in lymphocyte polarization pattern and increased systemic
      immunoreactivity. This process was ameliorated by anti-TNF-alpha and antiseptic
      therapies.

PMID- 22582750
TI  - Perspectives on providing good access to dental services for elderly people:
      patient selection, dentists' responsibility and budget management.
AB  - OBJECTIVES: To suggest a model for organizing and financing dental services for
      elderly people so that they have good access to services. BACKGROUND: There are
      few studies on how dental services for elderly people should be organized and
      financed. This is surprising if we take into consideration the fact that the
      proportion of elderly people is growing faster than any other group in the
      population, and that elderly people have more dental diseases and poorer access
      to dental services than the rest of the adult population. In several countries,
      dental services are characterized by private providers who often operate in a
      market with competition and free price-setting. Private dentists have no
      community responsibility, and they are free to choose which patients they treat.
      MATERIAL AND METHODS: Literature review and critical reasoning. RESULTS: In order
      to avoid patient selection, a patient list system for elderly people is
      recommended, with per capita remuneration for the patients that the dentist is
      given responsibility for. The patient list system means that the dentist assumes
      responsibility for a well-defined list of elderly people. CONCLUSION: Our model
      will lead to greater security in the dentist/patient relationship, and patients
      with great treatment needs will be ensured access to dental services.

PMID- 22582751
TI  - First observations of conjoined twins in newborn seahorses, Hippocampus
      guttulatus Cuvier.

PMID- 22582752
TI  - A new sesquiterpene lactone from Elephantopus tomentosus.
AB  - A new sesquiterpene lactone, named tomenphantopin H (1), together with two known
      germacranolides, 2beta-methoxy-2-deethoxy-8-O-deacylphantomolin-8-O-tiglinate (2)
      and 2-deethoxy-2-hydroxyphantomolin (3), was isolated from the whole plant of
      Elephantopus tomentosus Linn. The new compound was completely elucidated using a
      combination of 1D and 2D NMR techniques (COSY, HMQC, and HMBC) and HR-ESI-MS
      analyses. All compounds exhibited antibacterial activity.

PMID- 22582753
TI  - Application of EPR spectroscopy to identify irradiated Indian medicinal plant
      products.
AB  - A study of gamma-irradiated Indian medicinal plant products was carried out using
      electron paramagnetic resonance (EPR) spectroscopy. Improved approaches like high
      power measurement, microwave saturation, and thermal behavior of the radicals
      were explored for detection of irradiation. Aswagandha (Withania somnifera),
      vairi (Salacia reticulata), amla (Emblica officinalis), haldi (Curcumin longa),
      and guduchi (Tinospora cordifolia) exhibited a weak singlet at g = 2.005 before
      irradiation. Aswagandha, immediately after radiation treatment, revealed a
      complex EPR spectrum characterized by EPR spectrum simulation technique as
      superposition of 3 paramagnetic centers. One group of signal with organic origin
      was carbohydrate and cellulose radical and the other was isotropic signal of
      inorganic origin (g? =2.0044 and g|| = 1.9980). However, other products did not
      exhibit any radiation-specific signal after irradiation. Power saturation and
      thermal behavior techniques were not suitable for these products. However,
      amongst all the 3 approaches, high-power measurement of EPR spectra emerged as a
      suitable technique in identification of the irradiated aswagandha. PRACTICAL
      APPLICATION: Gamma-irradiation confirms hygienic quality and improves shelf life
      of food and other products. However, there is a lack of international consensus
      over considering this as a general application and different regulations are
      being enforced. EPR is one of the most promising techniques to identify
      irradiated foodstuffs for regulatory requirements but it has many limitations.
      Improved approaches based on the EPR technique explained in this study may be
      useful to identify irradiated products and become beneficial to food regulators
      and food irradiation enterprises to enhance confidence in irradiation technology.

PMID- 22582754
TI  - Polymer composition and substrate influences on the adhesive bonding of a
      biomimetic, cross-linking polymer.
AB  - Hierarchical biological materials such as bone, sea shells, and marine
      bioadhesives are providing inspiration for the assembly of synthetic molecules
      into complex structures. The adhesive system of marine mussels has been the focus
      of much attention in recent years. Several catechol-containing polymers are being
      developed to mimic the cross-linking of proteins containing 3,4
      dihydroxyphenylalanine (DOPA) used by shellfish for sticking to rocks. Many of
      these biomimetic polymer systems have been shown to form surface coatings or
      hydrogels; however, bulk adhesion is demonstrated less often. Developing
      adhesives requires addressing design issues including finding a good balance
      between cohesive and adhesive bonding interactions. Despite the growing number of
      mussel-mimicking polymers, there has been little effort to generate structure
      property relations and gain insights on what chemical traits give rise to the
      best glues. In this report, we examine the simplest of these biomimetic polymers,
      poly[(3,4-dihydroxystyrene)-co-styrene]. Pendant catechol groups (i.e., 3,4
      dihydroxystyrene) are distributed throughout a polystyrene backbone. Several
      polymer derivatives were prepared, each with a different 3,4-dihyroxystyrene
      content. Bulk adhesion testing showed where the optimal middle ground of cohesive
      and adhesive bonding resides. Adhesive performance was benchmarked against
      commercial glues as well as the genuine material produced by live mussels. In the
      best case, bonding was similar to that obtained with cyanoacrylate "Krazy Glue".
      Performance was also examined using low- (e.g., plastics) and high-energy (e.g.,
      metals, wood) surfaces. The adhesive bonding of poly[(3,4-dihydroxystyrene)-co
      styrene] may be the strongest of reported mussel protein mimics. These insights
      should help us to design future biomimetic systems, thereby bringing us closer to
      development of bone cements, dental composites, and surgical glues.

PMID- 22582755
TI  - Apple pomace is a good matrix for phytochemical retention.
AB  - Phytochemical content and color changes in dried apple pomace and pulp (mixture
      of Red Delicious and Golden Delicious varieties) were studied during 9 months
      storage in the water activity (a(w)) range 0.11-0.75 at 30  degrees C. Water
      mobility was measured at various a(w) levels by (1)H NMR. During storage,
      antioxidant degradation (including flavonols, flavanols, dihydrochalcones,
      anthocyanins, and hydroxycinnamic acids) followed first-order kinetics, whereas
      color changes followed zero-order kinetics. These changes were accelerated by
      increasing a(w). Phytochemical and color were more stable in the pomace than in
      the pulp over the entire a(w) range, having 2-6 times smaller degradation rates.
      These results were related to the lower water mobility found in apple pomace as
      compared to the pulp. The overall results show that apple pomace can be exploited
      as a food ingredient with good phytochemical retention, and may help in the
      development of new matrices with maximum phytochemical retention.

PMID- 22582756
TI  - High-efficiency ferroelectric-film solar cells with an n-type Cu2O cathode buffer
      layer.
AB  - Because of the existence of interface Schottky barriers and depolarization
      electric field, ferroelectric films sandwiched between top and bottom electrodes
      are strongly expected to be used as a new kind of solar cells. However, the
      photocurrent with a typical order of MUA/cm(2) is too low to be practical. Here
      we demonstrate that the insertion of an n-type cuprous oxide (Cu(2)O) layer
      between the Pb(Zr,Ti)O(3) (PZT) film and the cathode Pt contact in a ITO/PZT/Pt
      cell leads to the short-circuit photocurrent increasing 120-fold to 4.80 mA/cm(2)
      and power conversion efficiency increasing of 72-fold to 0.57% under AM1.5G (100
      mW/cm(2)) illumination. Ultraviolet photoemission spectroscopy and dark J-V
      characteristic show an ohmic contact on Pt/Cu(2)O, an n(+)-n heterojunction on
      Cu(2)O/PZT and a Schottky barrier on PZT/ITO, which provide a favorable energy
      level alignment for efficient electron-extraction on the cathode. Our work opens
      up a promising new method that has the potential for fulfilling cost-effective
      ferroelectric-film photovoltaic.

PMID- 22582757
TI  - Can watching traumatic events on TV cause PTSD symptoms? Evidence from Pakistan.

PMID- 22582758
TI  - Lysophosphatidic acid modulates the association of PTP1B with N-cadherin/catenin
      complex in SKOV3 ovarian cancer cells.
AB  - LPA (lysophosphatidic acid) is a natural phospholipid that plays important roles
      in promoting cancer cell proliferation, invasion and metastases. We previously
      reported that LPA induces ovarian cancer cell dispersal and disruption of AJ
      (adherens junction) through the activation of SFK (Src family kinases). In this
      study, we have investigated the regulatory mechanisms during the early phase of
      LPA-induced cell dispersal. An in vitro model of the ovarian cancer cell line
      SKOV3 for cell dispersal was used. LPA induces rapid AJ disruption by increasing
      the internalization of N-cadherin-beta-catenin. By using immunoprecipitations,
      LPA was shown to induce increased tyrosine phosphorylation of beta-catenin and
      alter the balance of beta-catenin-bound SFK and PTP1B (phosphotyrosine
      phosphatase 1B). The altered balance of tyrosine kinase/phosphatase correlated
      with a concomitant disintegration of the beta-catenin-alpha-catenin, but not the
      beta-catenin-N-cadherin complex. This disintegration of beta-catenin from alpha
      catenin and the cell dispersal caused by LPA can be rescued by blocking SFK
      activity with the chemical inhibitor, PP2. More importantly, PP2 also restores
      the level of PTP1B bound to beta-catenin. We propose that LPA signalling alters
      AJ stability by changing the dynamics of tyrosine kinase/phosphatase bound to AJ
      proteins. This work provides further understanding of the early signalling events
      regulating ovarian cancer cell dispersal and AJ disruption induced by LPA. 

PMID- 22582759
TI  - Assessing the preconditions for communication influence on decision making: the
      North American Quitline Consortium.
AB  - The network of North American quitlines is a loose confederation of telephone
      based smoking cessation professionals, including smoking cessation counseling
      providers, funders, researcher and policy advocates. Each quitline has some
      leeway in the types of services it provides, and the purpose of this article is
      to identify factors that explain such choices. Representatives from quitline
      organizations responded to a survey regarding the importance of several items
      that were hypothesized to influence general intentions to adopt and implement new
      cessation methods. Results indicate that internal (to the quitline) constraints
      are positively associated with consensus processes and that implementation of
      practices in general was more likely if consensus processes were used. Unilateral
      decision making (one person within an organization makes decisions for the
      quitline on his/her own) was unrelated to either internal or external constraints
      and was negatively associated with adoption of quitline practices. Discussion
      focuses on factors that influence consensus decision-making processes beyond
      those investigated in the article.

PMID- 22582760
TI  - The PEDALS stationary cycling intervention and health-related quality of life in
      children with cerebral palsy: a randomized controlled trial.
AB  - AIM: The aim of this study was to assess health-related quality of life (HRQOL)
      following a stationary cycling intervention in children with cerebral palsy (CP).
      METHOD: This was a phase I multisite randomized controlled trial with single
      blinding. HRQOL was evaluated using the Pediatric Quality of Life Inventory SF15
      (PedsQL; children) and Pediatric Outcomes Data Collection Instrument (PODCI;
      parent proxy) before and after a 3-month stationary cycling intervention. Sixty
      two children (29 male, 33 female; mean age 11y; range 7-18y) with spastic
      diplegic CP, classified as levels I to III on the Gross Motor Function
      Classification System, were enrolled. Paired and independent t-tests were used to
      evaluate within- and between-group differences respectively. RESULTS: Between
      group differences, favoring the cycling group, were found for PedsQL emotional
      functioning (p=0.046) and Parental PODCI treatment expectations scores (p=0.006).
      Between-group differences were not found for other scales. Within-group
      improvements were found in the cycling group: PedsQL total score (+5.8; p=0.006),
      psychosocial health summary (+6.9; p=0.008), and school functioning (+8.0;
      p=0.038). PODCI satisfaction with symptoms decreased significantly only in the
      control group (-12.0; p=0.046). INTERPRETATION: A beneficial influence of
      exercise on pediatric emotional well-being and parental treatment expectations
      was found. The evidence was not strong for other aspects of HRQOL. Results
      support the positive relationship between physical fitness and emotional well
      being in the general population. A child's perception is important when examining
      change in his or her emotional well-being due to intervention.

PMID- 22582761
TI  - The surface relaxation of water.
AB  - We examine three possible explanations for the millisecond relaxation time of the
      dynamic surface tension of water: the diffusion of surfactant contaminants from
      the aqueous phase to the surface, the reorientation of surface water molecules'
      dipole moments, and the buildup of a charged surface layer of hydroxide ions. The
      relaxation time expected for hydroxide is by far the closest to the measured
      time. Our model for the surface layer agrees with static equilibrium experiments
      and, as we show here, predicts the relaxation time. The results strongly imply
      that the equilibrium surface of water is highly charged by a flow of hydroxide to
      the surface. The model predicts that neither diffusion nor autolysis dominates
      and shows that both processes are needed to describe the relaxation of the
      surface tension. We find a salt and pH dependence of the relaxation time and
      propose further experiments.

PMID- 22582762
TI  - Usefulness of parathyroid hormone as a predictor of heart failure with preserved
      ejection fraction.
AB  - OBJECTIVE: To investigate the relation between parathyroid hormone (PTH) and
      heart failure with preserved ejection fraction (HF-PEF) in outpatients. METHODS:
      One hundred consecutive patients who had preserved left ventricular (LV) ejection
      fraction and heart failure (HF) symptoms, were enrolled. Echocardiography,
      assessing the diastolic functions was performed. Blood samples were collected for
      intact PTH and brain natriuretic peptide (BNP). RESULTS: Significant correlations
      between PTH level and predictors of advanced HF-PEF were found (p < 0.05). PTH
      level and left atrium diameter were found to be independent predictors of DHF.
      CONCLUSION: Measurement of serum PTH provides complementary information for the
      diagnosis and prognosis of HF-PEF.

PMID- 22582763
TI  - Next-of-kin's conceptions of medical technology in palliative homecare.
AB  - AIMS AND OBJECTIVES: Describe next-of-kin's conceptions of medical technology in
      palliative homecare. BACKGROUND: Next-of-kin to palliative patients are in an
      exposed position with increasing responsibility. The more involved they are in
      the care, the greater caregiver burden they describe. Medical technology has
      become increasingly common in palliative homecare, and previous research suggests
      that the devices transform the homes to a hospital ward, thus shifting
      responsibility from the personnel to the next-of-kin. DESIGN: An explorative
      descriptive design with a phenomenographic approach was chosen to describe
      qualitatively different conceptions of the phenomenon medical technology. METHOD:
      Interviews with 15 next-of-kin to patients in palliative homecare were analysed
      in a seven-step process where 10 conceptions emerged in five description
      categories. RESULTS: Medical technology in palliative homecare required next-of
      kin's responsibility in monitoring or providing practical help. It also implied
      uncertainty among the next-of-kin because of worries about its safety or because
      of an improper handling. The technology trespassed on daily life because it
      restricted and affected the private sphere. Medical technology enabled comfort as
      it implied security and was a prerequisite for the patient to be cared for at
      home. It also required an adjustment to comprehend and manage the medical
      technology. CONCLUSIONS: Medical technology resulted in an increased caregiver
      burden and uncertainty among the next-of-kin. Although it meant restrictions and
      affected their social life, they had great confidence in its possibilities.
      RELEVANCE TO CLINICAL PRACTICE: It is important to limit the amount of personnel
      and materials in the home to avoid trespassing on the family's daily life.
      Medical personnel also have to be sensitive to what next-of-kin have the strength
      to do and not use them as informal caregivers.

PMID- 22582764
TI  - Teacher-implemented joint attention intervention: pilot randomized controlled
      study for preschoolers with autism.
AB  - OBJECTIVE: The vast majority of children with an autism spectrum disorder (ASD)
      attend public preschools at some point in their childhood. Community preschool
      practices often are not evidence based, and almost none target the prelinguistic
      core deficits of ASD. This study investigated the effectiveness of public
      preschool teachers implementing a validated intervention (the Joint Attention and
      Symbolic Play/Engagement and Regulation intervention; JASP/ER) on a core deficit
      of autism, initiating joint attention. METHOD: Sixteen dyads (preschoolers with
      ASD and the public school teachers who worked in the child's classroom) were
      randomly assigned to the 6-week JASP/ER intervention or a control group. RESULTS:
      At the end of the intervention, JASP/ER teachers used more JASP/ER strategies
      than the control teachers, and JASP/ER preschoolers used more joint attention in
      their classroom than control children. Additionally, JASP/ER children spent more
      time in supported engagement and less time in object engagement than control
      preschoolers on a taped play interaction. CONCLUSIONS: Findings suggest that
      teachers were able to improve a core deficit of children with ASD in a public
      preschool context.

PMID- 22582765
TI  - Cognitive reappraisal self-efficacy mediates the effects of individual cognitive
      behavioral therapy for social anxiety disorder.
AB  - OBJECTIVE: To examine whether changes in cognitive reappraisal self-efficacy (CR
      SE) mediate the effects of individually administered cognitive-behavioral therapy
      (I-CBT) for social anxiety disorder (SAD) on severity of social anxiety symptoms.
      METHOD: A randomized controlled trial in which 75 adult patients (21-55 years of
      age; 53% male; 57% Caucasian) with a principal diagnosis of generalized SAD were
      randomly assigned to 16 sessions of I-CBT (n = 38) or a wait-list control (WL)
      group (n = 37). All patients completed self-report inventories measuring CR-SE
      and social anxiety symptoms at baseline and post-I-CBT/post-WL, and I-CBT
      completers were also assessed at 1-year posttreatment. RESULTS: Compared with WL,
      I-CBT resulted in greater increases in CR-SE and greater decreases in social
      anxiety. Increases in CR-SE during I-CBT mediated the effect of I-CBT on social
      anxiety. Gains achieved by patients receiving I-CBT were maintained 1-year
      posttreatment, and I-CBT-related increases in CR-SE were also associated with
      reduction in social anxiety at the 1-year follow-up. CONCLUSIONS: Increasing CR
      SE may be an important mechanism by which I-CBT for SAD produces both immediate
      and long-term reductions in social anxiety.

PMID- 22582766
TI  - MAML2 rearrangement in Warthin's tumour: a fluorescent in situ hybridisation
      study of metaplastic variants.
AB  - BACKGROUND: Warthin's tumour (WT) is a common benign lesion of the major salivary
      glands. The nature of WT remains controversial, with particular regard to the
      presence of clonal chromosomal abnormalities, including the t(11;19)
      translocation involving the CRTC1 and MAML2 genes, that have been identified in
      both WT and mucoepidermoid carcinoma. In this study, we focused our attention on
      metaplastic WT variants, and we conducted a fluorescent in situ hybridisation
      (FISH) analysis for the presence of MAML2 gene rearrangement. METHODS: Dual
      colour FISH analysis was performed on paraffin-embedded sections of eight WTs
      showing metaplastic changes (five with squamous metaplasia, two with mucinous
      metaplasia and one with both) using a MAML2 break-apart probe. RESULTS: Presence
      of split signals indicative of gene rearrangement was identified in a subset of
      cells in areas of squamous metaplasia in two samples of WT. No rearrangement was
      observed in the oncocytic epithelium, in lymphocytes and in areas of mucinous
      metaplasia. CONCLUSIONS: The presence of a small subpopulation of cells carrying
      MAML2 rearrangement in areas of squamous metaplasia within WT could predispose
      these lesions to malignant transformation in mucoepidermoid carcinoma and could
      represent a molecular link between the two entities.

PMID- 22582767
TI  - Importance of fundamental sp, sp2, and sp3 hydrocarbon radicals in the growth of
      polycyclic aromatic hydrocarbons.
AB  - The most basic chemistry of products formation in hydrocarbons pyrolysis has been
      explored via a comparative experimental study on the roles of fundamental sp,
      sp(2), and sp(3) hydrocarbon radicals/intermediates such as ethyne/ethynyl
      (C(2)H(2)/C(2)H), ethene/ethenyl (C(2)H(4)/C(2)H(3)), and methane/methyl
      (CH(4)/CH(3)) in products formations. By using an in situ time-of-flight mass
      spectrometry technique, gas-phase products of pyrolysis of acetylene (ethyne,
      C(2)H(2)), ethylene (ethene, C(2)H(4)), and acetone (propanone, CH(3)COCH(3))
      were detected and found to include small aliphatic products to large polycyclic
      aromatic hydrocarbons (PAHs) of mass 324 amu. Observed products mass spectra
      showed a remarkable sequence of mass peaks at regular mass number intervals of
      24, 26, or 14 indicating the role of the particular corresponding radicals,
      ethynyl (C(2)H), ethenyl (C(2)H(3)), or methyl (CH(3)), in products formation.
      The analysis of results revealed the following: (a) product formation in
      hydrocarbon pyrolysis is dominated by hydrogen abstraction and a vinyl (ethenyl,
      C(2)H(3)) radical addition (HAVA) mechanism, (b) contrary to the existing concept
      of termination of products mass growth at cyclopenta fused species like
      acenaphthylene, novel pathways forming large PAHs were found succeeding beyond
      such cyclopenta fused species by the further addition of C(2)H(x) or CH(3)
      radicals, (c) production of cyclopenta ring-fused PAHs (CP-PAHs) such as
      fluoranthene/corannulene appeared as a preferred route over benzenoid species
      like pyrene/coronene, (d) because of the high reactivity of the CH(3) radical, it
      readily converts unbranched products into products with aliphatic chains
      (branched product), and (e) some interesting novel products such as dicarbon
      monoxide (C(2)O), tricarbon monoxide (C(3)O), and cyclic ketones were detected
      especially in acetone pyrolysis. These results finally suggest that existing
      kinetic models of product formation should be modified to include the reported
      novel species and their formation pathways. It is expected that outcomes of this
      study will be useful to understand the products formation from reactors to
      interstellar atmospheres as well as the growth mechanism of carbon nanomaterials.

PMID- 22582768
TI  - Azepine synthesis from alkyl azide and propargylic ester via gold catalysis.
AB  - An efficient new method was developed to synthesize multisubstituted 4,5-dihydro
      1H-azepine derivatives through the gold-catalyzed reaction of two molecules of
      propargylic esters with one molecule of alkyl azide. It was proposed that vinyl
      gold carbenoid, in situ generated from propargylic ester through gold-catalyzed
      1,2-rearrangement, was trapped by alkyl azide to give vinyl imine intermediate.
      These, in turn, could undergo a formal [4 + 3] cycloaddition with another
      molecule of vinyl gold carbenoid to afford the desired azepine product.

PMID- 22582769
TI  - Association of bovine fatty acid composition with novel missense nucleotide
      polymorphism in the thyroid hormone-responsive (THRSP) gene.

PMID- 22582770
TI  - Prognostic value of the periodontal risk assessment in patients with aggressive
      periodontitis.
AB  - OBJECTIVES: Aim of the study was to evaluate the predictive value of the modified
      periodontal risk assessment (PRA) in patients with aggressive periodontitis (AgP)
      for the first time. MATERIAL AND METHODS: A total of 86 Patients with AgP were re
      examined 5-17 years after active periodontal treatment. Risk profile according to
      the modified PRA was assigned and regularity of maintenance monitored. Tooth
      loss, bone loss and recurrence of periodontitis were analysed in association with
      gender, diagnosis, compliance and risk profile using uni- and multivariate
      parametric regression and Cox proportional hazards models. RESULTS: A total of 14
      patients showed a localized AgP, 60 a high-risk-profile and 19 were compliant
      with the proposed maintenance-interval. Of 2202 teeth 98 were lost. Multivariate
      analysis could not assign a statistically significant impact to risk-profile. By
      excluding Interleukin-1 composite genotype from the modified PRA a significant
      influence (p = 0.003, HR 2.74) was detected. The impact of compliance was shown
      to be nearly significant (p = 0.059, HR 2.0). In patients with generalized AgP a
      tendency for increased tooth loss was found. CONCLUSION: The prognostic value of
      the modified PRA could not be confirmed in patients with AgP. However, exclusion
      of Interleukin-1 composite genotype led to a model with significant influence on
      tooth loss.

PMID- 22582771
TI  - Na+ absorption by Claudius' cells is regulated by purinergic signaling in the
      cochlea.
AB  - CONCLUSION: Claudius' cells absorb Na(+) through the amiloride-sensitive
      epithelial sodium channel (ENaC). Transepithelial ion transport through ENaC and
      possibly a Cl(-) secretory pathway is regulated by P2Y purinergic signaling.
      OBJECTIVES: The purpose of this study was to investigate ion transport in
      Claudius' cells and its purinergic regulation. METHODS: Young adult Sprague
      Dawley rats and gerbils were studied. The Claudius' cell layer on the basilar
      membrane was dissected from the basal turn of the cochlea. A voltage-sensitive
      vibrating probe was used to measure transepithelial short circuit current (I(sc)
      ). The baseline I(sc) of Claudius' cells was measured in the perilymph-like
      control solution and the change of I(sc) after application of amiloride (10 MUM)
      or uridine triphosphate (UTP, 100 MUM). RESULTS: A negative baseline I(sc) was
      observed in the control solution (-12.50 +/- 3.95 MUA/cm(2), n = 8) and the
      addition of amiloride resulted in a decrease of I(sc) by 75.8%. The application
      of UTP, an agonist for P2Y purinergic receptors, led to a partial inhibition of
      I(sc) (by 38.2 +/- 3.2%, n = 5), and subsequent addition of amiloride abolished
      the remaining I(sc).

PMID- 22582772
TI  - Enlarged vestibular aqueduct may precipitate benign paroxysmal positional vertigo
      in children.
AB  - CONCLUSIONS: Enlarged vestibular aqueduct (EVA) may precipitate secondary benign
      paroxysmal positional vertigo (BPPV), especially in pediatric populations, as
      well as paretic dysfunction of the vestibular end organ. OBJECTIVES: EVA is
      characterized by the early onset of sudden or progressive sensorineural hearing
      loss with or without vestibular dysfunction. However, vestibular dysfunction in
      patients with EVA has not been described as frequently as hearing loss, and an
      association with BPPV has not been previously reported. By reviewing the cochleo
      vestibular status of three children and two young adults with EVA who had been
      diagnosed with BPPV, characteristic features of BPPV in EVA patients were
      investigated and possible pathogenetic mechanisms are speculated. METHODS: A
      retrospective review of medical records was conducted for five patients with EVA
      who presented with BPPV from January 2004 to July 2009. Clinical courses,
      characteristics of vertigo and audiovestibular laboratory findings were reviewed.
      RESULTS: Among 26 patients with radiologically confirmed EVA, 5 (19.2%) exhibited
      positional nystagmus compatible with BPPV through Dix-Hallpike and head-roll
      tests. Hearing loss usually accompanied BPPV attacks, and BPPV was recurrent in
      three patients. Multiple semicircular canals were frequently involved in each
      episode, and different canals were also involved in recurrent cases. Canalith
      repositioning procedures were usually successful without difficulty.

PMID- 22582773
TI  - Expression of osmotic stress protein 94 in murine endolymphatic hydrops model.
AB  - CONCLUSION: The up-regulation of osmotic stress protein 94 (OSP94) in the murine
      endolymphatic hydrops (EH) models suggests that OSP94 might be involved in
      cellular adaptation in response to ionic and osmotic stress in the murine inner
      ear. OBJECTIVES: The purpose of the present study was to investigate the
      expression of OSP94 in cochlear tissues of the murine EH models and control
      animals. METHODS: Nine adult BALB/c mice were treated with both intratympanic
      injection of lipopolysaccharide and intraperitoneal administration of aldosterone
      to induce EH. Nine mice were used as control animals. The expression level of
      OSP94 in the EH and control groups was compared using immunohistochemistry and
      real-time RT-PCR. RESULTS: Immunohistochemical staining of tissues in the EH
      group showed an up-regulation of OSP94 expression in the cochlea, especially in
      the stria vascularis and Reissner's membrane. Quantitative real-time PCR analysis
      also showed that transcription of the OSP94 gene in the cochlea was significantly
      up-regulated in the EH group.

PMID- 22582774
TI  - Tracheal growth after airway stenosis surgery: serial radiographic comparative
      study.
AB  - CONCLUSION: The proportion of stenotic area over normal tracheal lumen does not
      decrease over time after airway stenosis surgery regardless of endoscopic or open
      surgery, which suggests that the operated laryngotracheal complex may grow and
      develop similarly to the normal surrounding tissue. OBJECTIVES: To evaluate the
      effect of pediatric airway stenosis surgery on the growth of the laryngotracheal
      complex and to compare the differences between endoscopic and open surgery.
      METHODS: Forty-five successful stoma closures after pediatric airway stenosis
      surgery were performed between 2001 and 2007. Thirty patients had a minimal
      postoperative follow-up time of 3 years and were included in this study.
      Evaluation was based on a retrospective review of the patients' images and data.
      The parameters analyzed were: diameter of tracheal stenosis, diameter of normal
      trachea, and the ratio of stenotic area to normal tracheal lumen. RESULTS: In
      all, 24 patients were treated with the endoscopic technique. Among the six open
      laryngotracheal reconstructions, cricoid splitting and rib cartilage graft were
      performed in four patients and laryngotracheal resection and end-to-end
      anastomosis were performed in two patients. Stenosis to normal ratio tended to
      increase after endoscopic intervention, but it did not show statistical
      significance (p = 0.082). Open surgery did not cause significant narrowing (p =
      0.443).

PMID- 22582775
TI  - Acoustic characteristics of snoring according to obstruction site determined by
      sleep videofluoroscopy.
AB  - CONCLUSION: Acoustic characteristics of snoring sound, such as pitch and formant,
      differed according to the site of upper airway obstruction determined by sleep
      videofluoroscopy (SVF). Snoring sound analysis can complement determination of
      the site of obstruction in snoring and sleep apnea patients. OBJECTIVES: The aim
      of this study was to evaluate the acoustic characteristics of snoring according
      to obstruction site determined by SVF. METHODS: Ninety patients who underwent
      simultaneous snoring sound recording during SVF were included in this study.
      Acoustic parameters of snoring such as pitch (min, mean, max) and formant (1,2)
      were analyzed. Site of obstruction was determined by SVF and classified according
      to anatomic structure and level of obstruction. RESULTS: Mean value of peak
      frequency showed significant difference between soft palate and isolated tongue
      base or epiglottis obstruction and combined obstruction involving soft palate and
      tongue base or epiglottis. Peak frequency of velopharyngeal obstruction showed
      difference only with hypopharyngeal obstruction. First formant showed similar
      results in the structure classification whereas velopharyngeal obstruction showed
      significant difference compared with other levels of obstruction. Other
      parameters (intensity, jitter, shimmer) did not show significance according to
      site of obstruction.

PMID- 22582776
TI  - Increased activity of mitochondrial respiratory chain complex in noise-damaged
      rat cochlea.
AB  - CONCLUSION: Functional changes of mitochondrial respiratory chain (MRC) and
      hearing threshold shifts were observed after noise exposure and the pattern was
      different depending on the extent of the noise damage. OBJECTIVES: The aim of
      this study was to reveal any functional changes of the MRC enzyme in outer hair
      cells after noise damage. METHODS: Sprague-Dawley rats were used and divided into
      three groups including normal control group and noise exposure for 1 h and 5 h.
      White band noise was used with 120 dB SPL. We measured hearing threshold and
      activity of succinate dehydrogenase (SDH) before noise exposure, and immediately
      and 1, 3, 7, and 14 days after noise exposure in each group. Immunostaining using
      monoclonal anti-MRC complex V subunit alpha was performed. Transmission electron
      microscopy (TEM) was carried out. RESULTS: The hearing threshold level changed
      depending on the exposure time in both the noise-exposed groups. In the 1 h
      group, hearing was improved after 1 day, and in the 5 h group, hearing was
      measured after 7 days. Changes in SDH activity were observed at the third day in
      the 1 h group and at the seventh day in the 5 h group. The expression level of
      MRC complex V was increased after noise exposure. TEM showed mitochondrial
      damage.

PMID- 22582777
TI  - Malignant tumors of the sinonasal tract in the pediatric population.
AB  - CONCLUSION: Sarcoma and lymphoma comprised 75% of 20 cases of pediatric sinonasal
      malignancies. As regards treatment, all 20 patients received chemotherapy and 6
      patients (30%) underwent surgery. The overall 5-year survival rate was 52%, with
      favorable outcome for solid tumors compared with lymphoma. OBJECTIVE: We aimed to
      investigate the clinical features and treatment outcomes of sinonasal
      malignancies in 20 pediatric patients. METHODS: Clinical features were evaluated
      and tumors were staged according to the staging system for each histologic type.
      RESULTS: The 20 patients consisted of 12 males and 8 females, ranging in age from
      1 to 16 years, with a median age of 9.6 years at diagnosis. More than half of the
      patients presented with nasal obstruction as the primary symptom, and mean
      symptom duration to diagnosis was 5.4 months. Primary tumor sites included the
      paranasal sinuses alone in four patients, the nasal cavity alone in eight, and
      both in eight. Eight tumors were sarcomas and seven were lymphomas. The remaining
      tumors included three olfactory neuroblastomas and two primitive neuroectodermal
      tumors. The main treatment modality was chemotherapy rather than surgery. The
      overall survival rate was 52%, and patients with solid tumors survived
      significantly longer than those with lymphoma (p = 0.02).

PMID- 22582778
TI  - Distorted olfactory perception: a systematic review.
AB  - The sense of smell provides people with valuable input from the chemical
      environment around them. The human sense of smell generally fails in three ways;
      one is an intensity reduction and the other two are the quality of changes. Smell
      disorders can be classified into central or peripheral depending on their origin.
      Central causes can be related to an area of hyper-functioning brain cells
      generating this odor perception, thus olfactory distortions have also been
      observed with epilepsy and migraine. In this paper, we present a review of the
      current clinical understanding of olfactory distortions and discuss how they can
      be evaluated and therapies to treat this debilitating condition.

PMID- 22582779
TI  - Clinical implications of rhinosinusitis detected by preoperative computed
      tomography for endoscopic endonasal transsphenoidal pituitary surgery.
AB  - CONCLUSIONS: Rhinosinusitis detected by preoperative osteomeatal unit computed
      tomography (OMU CT) may not increase the incidence of postoperative central
      nervous system (CNS) infections. OBJECTIVES: To evaluate the safety of endoscopic
      endonasal transsphenoidal pituitary surgery in patients who had rhinosinusitis
      detected by preoperative OMU CT. METHODS: A total of 107 patients who underwent
      endoscopic endonasal transsphenoidal pituitary surgery were enrolled. The
      presence of rhinosinusitis and the location of involved sinuses were assessed by
      preoperative OMU CT. The extent of pituitary tumors was assessed by preoperative
      sellar MRI. The occurrence of intraoperative cerebrospinal fluid (CSF) leakage
      and postoperative central nervous system (CNS) complications were analyzed using
      the medical records. The correlations between these variables and postoperative
      CNS complications were examined. RESULTS: After pituitary surgery, postoperative
      CNS complications occurred in four patients (3.7%). Twenty-eight patients (26.2%)
      had findings of rhinosinusitis on preoperative OMU CT. Of the 28 patients, 8 had
      rhinosinusitis in the anterior sinuses and 20 in the posterior sinuses.
      Intraoperative CSF leakage occurred in eight patients (7.5%). The occurrence of
      intraoperative CSF leakage showed a significant correlation with the incidence of
      postoperative CNS complications (p = 0.003) but not with the presence of
      rhinosinusitis (p = 0.134). Although not statistically significant, patients with
      rhinosinusitis in the posterior ethmoidal and/or sphenoidal sinuses tended to
      have higher incidences of postoperative CNS complications (p = 0.057).

PMID- 22582780
TI  - Histamine regulates mucin expression through H1 receptor in airway epithelial
      cells.
AB  - CONCLUSION: The data suggest that histamine up-regulates MUC2 gene regulation and
      mucin production in airway epithelial cells through histamine 1 receptor (H1R).
      Histamine appears to play an important role in the early phase of mucin
      regulation, which might be effectively blocked by an H1R antagonist. OBJECTIVE:
      Histamine is an important inflammatory mediator during the early phase of
      allergic response and antihistamine is known to have an ability to reduce mucus
      secretion in inflamed airways. The goal of the present study was to determine the
      effects of histamine on MUC2 gene expression and mucin secretion and to
      investigate the response to histamine 1 receptor (H1R) blocker in NCI-H292 cells
      and HM3-MUC2 cells. METHODS: NCI-H292 cells, a human pulmonary mucoepidermoid
      carcinoma cell line, and HM3-MUC2 cells transfected with MUC2 promoter (
      2,864/+19) pGL2 luciferase construct were used in the study. MUC2 mRNA expression
      was analyzed by RT-PCR for NCI-H292 cells and by luciferase assays for HM3-MUC2
      cells. MUC2 protein production was determined by immunoassay and
      immunofluorescent stain in NCI-H292 cells. RESULTS: Histamine increased MUC2 gene
      expression in a dose- and time-dependent manner. Peak response was reached at 12
      h after histamine administration. MUC2 protein production was also dose
      dependently increased, while it decreased with time in NCI-H292 cells.
      Pretreatment with histamine at a concentration of 1 mM induced MUC2 mRNAand
      protein production, which was equivalent to that caused by 10 ug/ml LPS, but less
      than that of 0.5 uM PMA. Histamine-induced MUC2 mRNA expression and mucin
      secretion were significantly suppressed by pretreatment with H1R antagonist.

PMID- 22582781
TI  - Otorhinolaryngology in Korea: a tribute to Professor Yang-Gi Min.

PMID- 22582782
TI  - Management of post-traumatic combined deviated and saddle nose deformity.
AB  - CONCLUSION: Establishing a straight and firm septum supporting the overlying
      nasal structures is the most important step in correcting the post-traumatic
      combined deviated and saddle nose. OBJECTIVES: To present a surgical algorithm
      and key maneuvers that were successfully applied in the correction of post
      traumatic combined deviated and saddle nose deformity. METHODS: Twenty-five
      patients who had undergone primary rhinoplasty for a post-traumatic combined
      deviated and saddle nose were included. The patterns of deformity, surgical
      maneuvers, surgical results, and complications were analyzed using retrospective
      chart review, telephone interview, and preoperative and postoperative
      photographs. RESULTS: Three distinct groups undergoing different techniques to
      correct the deformity were noted. Eighteen patients (72%) with intact septal
      support were treated by straightening the nose and septum followed by simple
      onlay grafts. Five patients (20%) with loss of septal support needed septal
      reconstruction. In two patients (8%) showing deviation, generalized saddling, and
      loss of septal support, a dorsal graft integrated to an extended columellar strut
      was performed, bypassing the major septal reconstruction. The key maneuvers for
      correction were dorsal onlay graft (100%), septoplasty (92%), and bilateral
      osteotomies (84%). No major complications were found. Objective evaluation showed
      complete correction of the deviation and saddling in 76%.

PMID- 22582783
TI  - Classification and prevalence of nasal septal deformity in Koreans according to
      two classification systems.
AB  - CONCLUSION: Guyuron type 2 and Mladina type 1 were the most common types of nasal
      septal deformity (NSD) in Koreans. The Guyuron classification showed a higher
      concordance rate with computed tomography (CT) findings than the Mladina
      classification. OBJECTIVES: The purpose of this study was to classify the NSD
      according to the Guyuron and Mladina classifications, and to evaluate the
      correlation between anterior rhinoscopy and CT findings. METHODS: Each septum of
      the patients who visited Seoul National University Hospital Health Care Center
      was classified according to the Guyuron and Mladina classifications. For the
      patients who underwent septoplasty, the correlation of NSD between anterior
      rhinoscopy and CT findings was evaluated. RESULTS: Of 970 patients, 50.3% had
      NSD. According to the Guyuron and Mladina classifications, type 2 (41.4%) and
      type 1 (35.4%) were most common, respectively. Among 64 patients who underwent
      septoplasty, the concordance rates with CT findings were 71.9% for the Guyuron
      classification and 50% for the Mladina classification. This difference was
      statistically significant (chi-squared test, p = 0.026).

PMID- 22582784
TI  - The role of mucosal immunity in fungus ball of the paranasal sinuses.
AB  - CONCLUSION: Increased levels of immunoglobulin (Ig)A, plasma cells, and
      lymphocytes without infiltration of other inflammatory cells suggest that mucosal
      immunity may play an important role in paranasal fungus ball. OBJECTIVES: This
      study aimed to examine the nasal mucosal immune responses to fungi to understand
      the pathogenesis of fungus ball. METHODS: Five patients with fungus ball of the
      maxillary sinus were enrolled. Lavage samples were collected from both nasal
      cavities and the maxillary sinus of the affected side. Mucosal samples were taken
      from both inferior turbinates and the maxillary sinus of the affected side.
      Interleukin (IL)-4, interferon (IFN)-gamma, and IgA levels in the lavage samples
      were measured. Cells were counted on the lamina propria of mucosa under an
      electron microscope. RESULTS: No significant differences in levels of IL-4 and
      IFN-gamma were observed between the three groups of lavage samples. However, a
      significant rise in IgA levels was observed in the lavage samples from the nasal
      cavity and maxillary sinus of the affected side compared with that of the
      contralateral nasal cavity. Infiltration of plasma cells and lymphocytes in
      mucosal samples from the inferior turbinate and maxillary sinus of the affected
      side was significantly increased compared with that from the contralateral
      inferior turbinate, but other inflammatory cells were few and showed no
      difference.

PMID- 22582785
TI  - Blocking interleukin-17 attenuates enhanced inflammation by staphylococcal
      enterotoxin B in murine allergic rhinitis model.
AB  - CONCLUSION: The results of this study suggest that staphylococcal enterotoxin B
      (SEB) enhances inflammation in allergic rhinitis (AR) and interleukin (IL)-17 may
      play a significant role in regulation of the inflammatory process induced by SEB.
      OBJECTIVES: Exposure to SEB is associated with severe symptoms in AR patients.
      However, how SEB influences the inflammatory process in AR has not been
      elucidated so far. The aim of this study was to identify the role of SEB and IL
      17 in AR. METHODS: BALB/c and IL-17-deficient mice were divided into three
      groups: control, OVA, and SEB groups. The control group was challenged with
      phosphate-buffered saline, the AR group was challenged with ovalbumin (OVA), and
      the SEB group was treated with SEB before OVA challenge. Nasal symptoms,
      eosinophil infiltration, serum total and OVA-specific immunoglobulin E levels,
      and cytokine levels including IL-1beta, IL-4, IL-6, and interferon (IFN)-gamma in
      splenocyte culture were compared between the groups. RESULTS: The SEB group
      produced significantly greater amounts of cytokines such as IL-1beta, IL-4, IL-6,
      and IFN-gamma than the OVA group in wild-type mice. However, these enhanced
      inflammatory responses in the SEB group compared with the OVA group were not
      observed in IL-17-deficient mice.

PMID- 22582786
TI  - Analysis of genetic expression in the soft palate of patients with obstructive
      sleep apnea.
AB  - CONCLUSION: Genetic dysregulation may be associated with development of
      obstructive sleep apnea (OSA). OBJECTIVES: Genetic expression was investigated in
      the soft palate of patients with OSA to evaluate the biomolecular characteristics
      of the tissue where airway obstruction actually occurs. METHODS: Soft palate
      mucosa was obtained during uvulopalatal flap surgery. Three patients with
      apnea/hypopnea index (AHI) >30/h and three simple snoring patients with AHI < 5/h
      were enrolled. After total RNA was extracted and amplified, gene expression
      levels were determined by microarray analysis, and relative signal intensities
      for each gene were evaluated. RESULTS: Of the 45,034 genes analyzed, 137 were up
      regulated in OSA patients compared with simple snorers and 95 were down
      regulated. Gene network analysis showed that genes related to RNA interference
      and transcription were most commonly involved in the functional pathophysiology
      of OSA. In particular, genes encoding proliferating cell nuclear antigen and
      proteasome 26S subunit ATPase 6 were functionally connected with other genes.

PMID- 22582787
TI  - Feasibility of the nasoseptal flap for reconstruction of large anterior skull
      base defects in Asians.
AB  - CONCLUSION: Reconstruction of a large anterior skull base defect (SBD) with the
      nasoseptal flap (SF) is feasible in Asians. We consider the width of the SF to be
      the determining factor. Increasing flap width by incorporating the mucoperiosteum
      of the nasal floor can compensate for the relatively small septum in Asians.
      OBJECTIVES: To assess the feasibility of the SF for reconstruction of large
      anterior SBD in Koreans, and attempt to provide tips for improving its design.
      METHODS: Radioanatomic measurements and intraoperative findings were analyzed.
      Specific skull base landmarks were measured to estimate the anticipated SBD and
      actual SBD. The length and width of the potential SF dimension was also measured
      and compared with the defect size to assess its feasibility. RESULTS: The lengths
      of the actual SBDs were longer than those of anticipated SBDs in all patients,
      while the width of actual SBDs showed less discrepancy. Length and anterior width
      of the potential SF exceeded the needed SF dimensions in two patients, while the
      posterior width of potential SF fell short of the needed dimension. In both
      patients, the length of harvested SF was long enough to repair the entire length
      of SBD, while shortage of SF width was encountered in one patient.

PMID- 22582788
TI  - Treatment outcomes and predictors for systemic steroids in nasal polyposis.
AB  - CONCLUSION: Systemic steroids improve nasal symptoms such as sneezing, purulent
      rhinorrhea, and nasal obstruction in patients with nasal polyposis, regardless of
      measurable response to systemic steroid. A history of allergic rhinitis is an
      independent prognostic factor for favorable response of nasal polyposis to
      systemic steroid. Overexpression of glucocorticoid receptor beta is associated
      with glucocorticoid resistance. OBJECTIVES: This study was conducted to evaluate
      treatment outcomes and clinically useful predictive factors for systemic steroids
      in nasal polyposis. METHODS: The study involved 47 consecutive patients diagnosed
      with nasal polyposis from December 2008 to May 2010. Twenty milligrams of
      prednisolone were administered daily for 14 days. The following parameters were
      analyzed: subjective nasal symptoms, history of allergic rhinitis and asthma,
      SNOT-20 score, olfactory function test, bronchial hyperreactivity, blood
      eosionophil count, atopy, Lund-Mackay score, tissue eosinophil infiltration
      ratio, and expression of glucocorticoid receptor alpha and beta in the nasal
      polyp epithelium. RESULTS: In all, 62% of the patients were responders, i.e. had
      a decreased polyp size >25% after treatment. SNOT-20 score tended to decrease for
      all patients but significantly only for the responder group (p < 0.01). Eighteen
      of the responders had a medical history of allergic rhinitis, but only five of
      the nonresponders did (p = 0.026, Odds ratio = 4.26). Responder group polyps
      showed significantly less immunoreactivity of glucocorticoid receptor beta than
      polyps from the nonresponder group.

PMID- 22582790
TI  - Intravenous administration of human mesenchymal stem cells after noise- or drug
      induced hearing loss in rats.
AB  - CONCLUSION: Systemic application of human mesenchymal stem cells (hMSCs) may be
      another effective tool for stem cell supply to the inner ear. OBJECTIVES: Most
      researchers have used local application to provide the inner ear with stem cells.
      In spite of their efficacy, these methods can potentially cause irreversible
      damage to the inner ear. A homing phenomenon of systemically administered MSCs to
      the ischemic myocardium and brain was recently reported. Moreover, hMSCs have
      several advantages over conventional neural or embryonic stem cells. Thus we
      hypothesized that intense noise or ototoxic injury to the cochlea could induce
      the homing of hMSCs. METHODS: We harvested hMSCs from bone marrow of the iliac
      crest of five normal individuals. Then hMSCs at a dose of 4 * 10(6) cells were
      given via intravenous injection of cell suspension into rats with cochleae
      damaged by noise or ototoxic drugs. Histological analysis was undertaken 30 days
      later. RESULTS: Systemically delivered hMSCs were usually largely entrapped in
      the lungs. However, we documented the homing of some hMSCs to the cochlea with
      degenerated inner hair cells. The recruitment of hMSCs was limited to the spiral
      ganglion area only. The migration of donor cells into the cochlea was accompanied
      by the expression of brain-derived neurotrophic factor (BDNF).

PMID- 22582789
TI  - Clinical efficacy of sublingual immunotherapy in pediatric patients with allergic
      rhinitis sensitized to house dust mites: comparison to adult patients.
AB  - CONCLUSION: Sublingual immunotherapy (SLIT) with house dust mite (HDM) extracts
      in school-age children and adolescents seems to be as effective as in adults.
      SLIT could be recommended as a therapeutic modality in pediatric allergic
      rhinitis (AR) patients sensitized to HDMs. OBJECTIVES: To investigate the
      efficacy of HDM SLIT in pediatric patients with AR. MATERIALS AND METHODS:
      Seventy-six patients treated with HDM SLIT for at least 1 year between November
      2007 and February 2010 were enrolled in this study. A young age group (n = 54)
      between 6 and 18 years old was compared with an adult group (n = 22).
      Standardized extract of HDM (Pangramin(r) SLIT) was used. Total symptom scores
      (TSS) and anti-allergic medication scores (AMS) were evaluated before and 1 year
      after SLIT. RESULTS: TSS improved in both groups, and the change was comparable
      in the 2 groups (DeltaTSS, 5.1 vs 5.3; p = 0.538). Also among the young age
      group, DeltaTSS did not significantly differ between school-age children and
      adolescents (5.2 vs 4.9, p = 0.429). Thirty-five out of 54 youngsters (64.8%) and
      11 out of 22 adults (50.0%) showed improvement in TSS over 30%. AMS were
      significantly decreased in both groups. DeltaAMS tended to be higher in the young
      age group, but the difference did not reach statistical significance (57.2 vs
      35.7, p = 0.060).

PMID- 22582791
TI  - Alternative interactions define gyrase specificity in the CcdB family.
AB  - Toxin-antitoxin (TA) modules are small operons associated with stress response of
      bacteria. F-plasmid CcdB(F) was the first TA toxin for which its target, gyrase,
      was identified. Plasmidic and chromosomal CcdBs belong to distinct families.
      Conserved residues crucial for gyrase poisoning activity of plasmidic CcdBs are
      not conserved among these families. Here we show that the chromosomal CcdB(Vfi)
      from Vibrio fischeri is an active gyrase poison that interacts with its target
      via an alternative energetic mechanism. Changes in the GyrA14-binding surface of
      the Vibrio and F-plasmid CcdB family members illustrate neutral drift where
      alternative interactions can be used to achieve the same functionality.
      Differences in affinity between V. fischeri and F-plasmid CcdB for gyrase and
      their corresponding CcdA antitoxin possibly reflect distinct roles for TA modules
      located on plasmids and chromosomes.

PMID- 22582792
TI  - Efficacy of Fungiflora Y staining for the diagnosis of oral erythematous
      candidiasis.
AB  - OBJECTIVE: The purpose of this study was to investigate the efficacy of
      Fungiflora Y staining (fluorescent stain) for the diagnosis of erythematous
      candidiasis. SUBJECTS AND METHODS: This study enrolled 48 patients who were
      diagnosed with erythematous candidiasis and who underwent fungal culture and
      microscopic examination of a smear specimen stained with CytoQuick (modification
      of the Giemsa stain) and Fungiflora Y. Fungiflora Y staining was observed using a
      portable fluorescent microscope (CyScope((r))). The sensitivity, specificity and
      positive and negative predictive values were calculated using fungal culture as
      the gold standard test. Accuracy was calculated, and the difference between the
      CytoQuick and Fungiflora Y groups was examined using contingency tables and the
      chi-square test. RESULTS: The sensitivity and specificity of the CytoQuick stain
      was 0.51 and 0.91, respectively; the positive predictive value was 0.95, and the
      negative predictive value was 0.36. The sensitivity and specificity of the
      Fungiflora Y stain was 0.84 and 1.0, respectively; the positive predictive value
      was 1.00, and the negative predictive value was 0.65. The accuracy of Fungiflora
      Y (0.88) was superior to that of CytoQuick (0.60) (p = 0.0052). CONCLUSIONS:
      Microscopic examinations of smear specimens using a combination of Fungiflora Y
      staining and the CyScope((r)) portable fluorescent microscope was found to be
      useful for the diagnosis of oral erythematous candidiasis.

PMID- 22582793
TI  - Persistence of viral RNA in fish infected with VHSV-IVb at 15 degrees C and then
      moved to warmer temperatures after the onset of disease.
AB  - Smallmouth bass, Micropterus dolomieu Lacepede, bluegill, Lepomis macrochirus
      Rafinesque (coppernose strain), koi carp, Cyprinus carpio L., and channel catfish
      Ictalurus punctatus (Rafinesque), were infected by intraperitoneal injection with
      viral haemorrhagic septicaemia virus genotype IVb (VHSV-IVb) at 15  degrees C.
      When clinical signs of disease developed, one-third of the fish was moved to 20
      degrees C and one-third to 25 degrees C. Mortality in challenged fish at all
      three temperatures ranged from 25 to 45% in smallmouth bass and from 70 to 90% in
      bluegill. No koi carp or channel catfish died during the study. Viral copy
      numbers detected by quantitative real-time reverse transcriptase PCR (qrt-RTPCR)
      in fish dying at 20 and 25 degrees C decreased over time. In survivors of the
      challenge, viral copy numbers were higher in the more susceptible species
      (smallmouth bass and bluegill) than in the more VHSV-IVb disease-resistant
      species (koi carp and channel catfish). In fish surviving 28days post-infection,
      prevalence of infection was 66-100% depending on species and temperature, and
      VHSV-IVb was detected at 10(3) -10(5) copies MUg(-1) host RNA. Our results show
      that qrt-RTPCR is a useful tool to investigate fish kills even 28days after
      temperatures are elevated above those known to be permissive for VHSV
      replication.

PMID- 22582794
TI  - Formation of N719 dye multilayers on dye sensitized solar cell photoelectrode
      surfaces investigated by direct determination of element concentration depth
      profiles.
AB  - The structure of the dye layer adsorbed on the titania substrate in a dye
      sensitized solar cell is of fundamental importance for the function of the cell,
      since it strongly influences the injection of photoelectrons from the excited dye
      molecules into the titania substrate. The adsorption isotherms of the N719
      ruthenium-based dye were determined both with a direct method using the depth
      profiling technique neutral impact collision ion scattering spectroscopy (NICISS)
      and with the standard indirect solution depletion method. It is found that the
      dye layer adsorbed on the titania surface is laterally inhomogeneous in thickness
      and there is a growth mechanism already from low coverage levels involving a
      combination of monolayers and multilayers. It is also found that the amount of
      N719 adsorbed on the substrate depends on the titania structure. The present
      results show that dye molecules in dye-sensitized solar cells are not
      necessarily, as presumed, adsorbed as a self-assembled monolayer on the
      substrate.

PMID- 22582795
TI  - Sterilizable gels from thermoresponsive block copolymer worms.
AB  - Biocompatible hydrogels have many applications, ranging from contact lenses to
      tissue engineering scaffolds. In most cases, rigorous sterilization is essential.
      Herein we show that a biocompatible diblock copolymer forms wormlike micelles via
      polymerization-induced self-assembly in aqueous solution. At a copolymer
      concentration of 10.0 w/w %, interworm entanglements lead to the formation of a
      free-standing physical hydrogel at 21  degrees C. Gel dissolution occurs on
      cooling to 4  degrees C due to an unusual worm-to-sphere order-order transition,
      as confirmed by rheology, electron microscopy, variable temperature (1)H NMR
      spectroscopy, and scattering studies. Moreover, this thermo-reversible behavior
      allows the facile preparation of sterile gels, since ultrafiltration of the
      diblock copolymer nanoparticles in their low-viscosity spherical form at 4 
      degrees C efficiently removes micrometer-sized bacteria; regelation occurs at 21 
      degrees C as the copolymer chains regain their wormlike morphology.
      Biocompatibility tests indicate good cell viabilities for these worm gels, which
      suggest potential biomedical applications.

PMID- 22582796
TI  - Microscopy beyond the diffraction limit using actively controlled single
      molecules.
AB  - In this short review, the general principles are described for obtaining
      microscopic images with resolution beyond the optical diffraction limit with
      single molecules. Although it has been known for several decades that single
      molecule emitters can blink or turn on and off, in recent work the addition of
      on/off control of molecular emission to maintain concentrations at very low
      levels in each imaging frame combined with sequential imaging of sparse subsets
      has enabled the reconstruction of images with resolution far below the optical
      diffraction limit. Single-molecule active control microscopy provides a powerful
      window into information about nanoscale structures that was previously
      unavailable.

PMID- 22582797
TI  - Three-dimensional motion tracking for high-resolution optical microscopy, in
      vivo.
AB  - When conducting optical imaging experiments, in vivo, the signal to noise ratio
      and effective spatial and temporal resolution is fundamentally limited by
      physiological motion of the tissue. A three-dimensional (3D) motion tracking
      scheme, using a multiphoton excitation microscope with a resonant galvanometer,
      (512 * 512 pixels at 33 frames s(-1)) is described to overcome physiological
      motion, in vivo. The use of commercially available graphical processing units
      permitted the rapid 3D cross-correlation of sequential volumes to detect
      displacements and adjust tissue position to track motions in near real-time.
      Motion phantom tests maintained micron resolution with displacement velocities of
      up to 200 MUm min(-1), well within the drift observed in many biological tissues
      under physiologically relevant conditions. In vivo experiments on mouse skeletal
      muscle using the capillary vasculature with luminal dye as a displacement
      reference revealed an effective and robust method of tracking tissue motion to
      enable (1) signal averaging over time without compromising resolution, and (2)
      tracking of cellular regions during a physiological perturbation.

PMID- 22582798
TI  - Effects of focused ion beam milling on electron backscatter diffraction patterns
      in strontium titanate and stabilized zirconia.
AB  - This study investigates the effect of focused ion beam (FIB) current and
      accelerating voltage on electron backscatter diffraction pattern quality of
      yttria-stabilized zirconia (YSZ) and Nb-doped strontium titanate (STN) to
      optimize data quality and acquisition time for 3D-EBSD experiments by FIB serial
      sectioning. Band contrast and band slope were used to describe the pattern
      quality. The FIB probe currents investigated ranged from 100 to 5000 pA and the
      accelerating voltage was either 30 or 5 kV. The results show that 30 kV FIB
      milling induced a significant reduction of the pattern quality of STN samples
      compared to a mechanically polished surface but yielded a high pattern quality on
      YSZ. The difference between STN and YSZ pattern quality is thought to be caused
      by difference in the degree of ion damage as their backscatter coefficients and
      ion penetration depths are virtually identical. Reducing the FIB probe current
      from 5000 to 100 pA improved the pattern quality by 20% for STN but only showed a
      marginal improvement for YSZ. On STN, a conductive coating can help to improve
      the pattern quality and 5 kV polishing can lead to a 100% improvement of the
      pattern quality relatively to 30 kV FIB milling. For 3D-EBSD experiments of a
      material such as STN, it is recommended to combine a high kV FIB milling and low
      kV polishing for each slice in order to optimize the data quality and acquisition
      time.

PMID- 22582799
TI  - Automatic measurement of compression wood cell attributes in fluorescence
      microscopy images.
AB  - This paper presents a new automated method for analyzing compression wood fibers
      in fluorescence microscopy. Abnormal wood known as compression wood is present in
      almost every softwood tree harvested. Compression wood fibers show a different
      cell wall morphology and chemistry compared to normal wood fibers, and their
      mechanical and physical characteristics are considered detrimental for both
      construction wood and pulp and paper purposes. Currently there is the need for
      improved methodologies for characterization of lignin distribution in wood cell
      walls, such as from compression wood fibers, that will allow for a better
      understanding of fiber mechanical properties. Traditionally, analysis of
      fluorescence microscopy images of fiber cross-sections has been done manually,
      which is time consuming and subjective. Here, we present an automatic method,
      using digital image analysis, that detects and delineates softwood fibers in
      fluorescence microscopy images, dividing them into cell lumen, normal and highly
      lignified areas. It also quantifies the different areas, as well as measures cell
      wall thickness. The method is evaluated by comparing the automatic with a manual
      delineation. While the boundaries between the various fiber wall regions are
      detected using the automatic method with precision similar to inter and intra
      expert variability, the position of the boundary between lumen and the cell wall
      has a systematic shift that can be corrected. Our method allows for transverse
      structural characterization of compression wood fibers, which may allow for
      improved understanding of the micro-mechanical modeling of wood and pulp fibers.

PMID- 22582800
TI  - The structure of nanocomposite 1D cationic conductor crystal@SWNT.
AB  - Nanocomposites consisting of one-dimensional (1D) crystals of the cationic
      conductors CuI, CuBr and AgBr inside single-walled carbon nanotubes, mainly (n,
      0), were obtained using the capillary technique. 1D crystal structure models were
      proposed based on the high resolution transmission electron microscopy performed
      on a FEI Titan 80-300 at 80 kV with aberration correction. According to the
      models and image simulations there are two modifications of 1D crystal: hexagonal
      close-packed bromine (iodine) anion sublattice (growth direction <001>) and 1D
      crystal cubic structure (growth direction <112>) compressed transversely to the
      nanotube (D(m) ~1.33 nm) axis. Tentatively this kind of 1D crystal can be
      considered as monoclinic. One modification of the anion sublattice reversibly
      transforms into the other inside the nanotube, probably initiated by electron
      beam heating. As demonstrated by micrographs, copper or silver cations can occupy
      octahedral positions or are statistically distributed across two tetrahedral
      positions. A 1DAgBr@SWNT (18, 0; 19, 0) pseudoperiodic 'lattice distortion' is
      revealed resulting from convolution of the nanotube wall function image with 1D
      cubic crystal function image.

PMID- 22582801
TI  - Comment on Yakovlev, S. & Downing, K.H. (2011) Crystalline ice as a
      cryoprotectant: theoretical calculation of cooling speed in capillary tubes. J.
      Microsc. 243, 8-14.

PMID- 22582802
TI  - Use of the pre-operative shuttle walk test to predict morbidity and mortality
      after elective major colorectal surgery.
AB  - High-risk surgery is performed in every acute hospital. These patients often have
      increased peri-operative risk related to their poor cardiorespiratory reserve.
      Formal risk assessment is recommended for such patients; cardiopulmonary exercise
      testing is a well established triage tool, but is unavailable in many hospitals.
      We investigated whether a simple exercise test could predict postoperative
      outcome using a prospective trial of 121 patients undergoing elective major
      abdominal surgery. Each patient completed a shuttle walk test and was followed up
      for 30 days after surgery. There was one postoperative death (0.8%), with 53
      patients (44%) developing complications. The mean (SD) shuttle walk test distance
      was significantly different between patients who suffered complications and those
      who did not (276.6 (134.5) vs 389.6 (138.9) m, respectively; p < 0.001). A cut
      off distance of 250 m had a specificity of 0.88 and a sensitivity of 0.58 to
      predict postoperative complications. Patients unable to complete a shuttle walk
      test above this cut-off distance were three times more likely to have a
      postoperative morbidity. We conclude that the shuttle walk test can help identify
      patients who are at increased peri-operative risk.

PMID- 22582804
TI  - Protective effects of sinomenine against doxorubicin-induced nephrosis in rats.
AB  - Sinomenine (SN, 1) is a pure compound extracted from the Sinomenium acutum plant.
      We investigated the protective effects and mechanism of action of SN in a rat
      model of doxorubicin (DOX)-induced nephrosis. Nephrosis was induced by a single
      dose of 5 mg/kg DOX, and DOX-treated rats received a daily i.p. injection of 10
      or 30 mg/kg SN, or saline (n = 6). Urine and serum biochemical parameters, serum
      TNF-alpha and IL-1beta levels, nephrin, podocin, alpha-actinin-4, and peroxisome
      proliferator-activated receptor-alpha (PPAR-alpha) protein expression, and renal
      ultrastructure were examined at day 28. Compound 1 significantly attenuated the
      effect of DOX on urine and serum biochemical parameters. Electron microscopy
      demonstrated that 1 suppressed DOX-induced increases in foot process width.
      Compared with those in control rats, nephrin, podocin, and PPAR-alpha protein
      expressions decreased in the glomeruli of DOX-treated rats, and this effect was
      significantly attenuated by 1. However, no appreciable alterations were observed
      in the expression level of alpha-actinin-4. DOX significantly increased serum TNF
      alpha and IL-1beta compared with those in control rats, and 1 significantly
      reduced the serum levels of TNF-alpha and IL-1beta. SN ameliorates DOX-induced
      nephrotic syndrome in rats, resulting in a modulation of renal nephrin, podocin
      expression, and thereby protecting podocytes from injury.

PMID- 22582805
TI  - Changes in the level of serum high-temperature requirement A1 (HtrA1) during
      pregnancy and its relationship to preeclampsia.
AB  - OBJECTIVE: To investigate the expression and changes of high-temperature
      requirement A1 (HtrA1) during pregnancy and the use of this value in predicting
      preeclampsia. METHOD: Serum samples were collected from pregnant mothers at
      different gestational weeks, and double-antibody sandwich enzyme-linked
      immunosorbent assay was employed to describe the changes in HtrA1 in serum during
      pregnancy. RESULTS: (i) In Xi'an area of China, the incidence of preeclampsia was
      4.95%, including 0.85% of early-onset type and 4.10% of late-onset type; (ii) the
      HtrA1 showed a lognormal distribution during pregnancy in the maternal serum,
      with the peak at 17-20 weeks of pregnancy; (iii) the HtrA1 levels in preeclampsia
      mothers peaked at 13-16 weeks of pregnancy, followed by acute decline until 21-24
      weeks, then remained stable; (iv) the HtrA1 levels in preeclampsia mothers were
      higher than the control group in 13-16 weeks and lower than that in 21-24 weeks
      (p < 0.05); (v) the criteria using lgHtrA1 level at 1.684 during 13-16 weeks of
      pregnancy could predict hypertension disorders complicating pregnancy (HDCP) with
      sensitivity of 62.1% and specificity of 53.7%. This could be improved to 85 and
      83%, respectively, when combined with body mass index as well as education
      background of the mother. CONCLUSION: (i) HtrA1 showed lognormal distribution
      during pregnancy for all populations; (ii) HtrA1 level peaked at 17-20 weeks in
      normal group of pregnant mothers, and the increase of HtrA1 level in 13-16 weeks
      could predict the risk of preeclampsia; (iii) the risk calculation formula for
      preeclampsia: p (%) = eY/(1 + eY) (Y = -15.87 + 3.706 * lgHtrA1 + 0.134 * mean
      arterial pressure (MAP) - 1.4 * education level code); e = 2.718.

PMID- 22582803
TI  - Photochemically inactivated hepatitis B virus promotes upregulation of Th1-type
      cytokines.
AB  - Photochemical virus inactivation technology is widely used to improve the safety
      of blood products. However, the process by which this inactivation occurs and the
      resulting immunogenicity of treated viruses remain to be elucidated. This study
      aimed to explore the effects of two photochemical inactivation methods (methylene
      and riboflavin, MP and RP) on hepatitis B virus (HBV) immunogenicity. Inactivated
      HBV were incubated with PBMC from six healthy donors. Culture supernatants were
      collected at 0, 24 and 72 h for the analysis of HBsAg and HBeAg expression using
      ELISA. Cytokine expression was analyzed at 72 h using ELISA. Costimulatory and
      cell adhesion molecule mRNA expression was analyzed at 24 h by RT-PCR. No
      significant changes in HBsAg and HBeAg were detected following MP. However, the
      secretion of TNF-alpha and IFN-gamma was upregulated. Expression of CD80, CD86,
      ICAM2 and LFA3 mRNA was also upregulated. In contrast, although RP did not
      significantly alter HBsAg expression, a reduction in HBeAg expression was
      observed. Furthermore, no upregulation of cytokines and intracellular molecule
      expression was observed following RP. These data indicate that the immunogenicity
      of HBV is retained following MP, and the inactivation of HBV could upregulate the
      Th1-type cellular immune responses, which may play significant roles in the
      antiviral process.

PMID- 22582806
TI  - PROLIX: rapid mining of protein-ligand interactions in large crystal structure
      databases.
AB  - A central problem in structure-based drug design is understanding protein-ligand
      interactions quantitatively and qualitatively. Several recent studies have
      highlighted from a qualitative perspective the nature of these interactions and
      their utility in drug discovery. However, a common limitation is a lack of
      adequate tools to mine these interactions comprehensively, since exhaustive
      searches of the protein data bank are time-consuming and difficult to perform.
      Consequently, fundamental questions remain unanswered: How unique or how common
      are the protein-ligand interactions observed in a given drug design project when
      compared to all complexed structures in the protein data bank? Which interaction
      patterns might explain the affinity of a tool compound toward unwanted targets?
      To answer these questions and to enable the systematic and comprehensive study of
      protein-ligand interactions, we introduce PROLIX (Protein Ligand Interaction
      Explorer), a tool that uses sophisticated fingerprint representations of protein
      ligand interaction patterns for rapid data mining in large crystal structure
      databases. Our implementation strategy pursues a branch-and-bound technique that
      enables mining against thousands of complexes within a few seconds. Key elements
      of PROLIX include (i) an intuitive interface that enables users to formulate
      complex queries easily, (ii) exceptional speed for results retrieval, and (iii) a
      sophisticated results summarization. Herein we describe the algorithms developed
      to enable complex queries and fast retrieval of search results, as well as the
      intuitive aspects of the user interface and summarization viewer.

PMID- 22582807
TI  - Hydrophobic moments, shape, and packing in disordered proteins.
AB  - Disordered proteins play a significant role in many biological processes and
      provide an attractive target for biophysical studies under physiological
      conditions. Disordered proteins may be classified as (a) proteins with overall
      well-defined secondary structures, interspersed with regions of missing residues,
      or (b) natively unstructured proteins which lack definite secondary structure.
      The spatial profile of second order hydrophobic moment for disordered proteins
      depicts the distribution of hydrophobic residues from the interior to the surface
      of the protein and indicates the lack of a well-formed hydrophobic core unlike
      that of the globular proteins. This trend is independent of the size or position
      of the disordered region in the sequence. The hydrophobicity profile of the
      ordered regions of the disordered proteins differ considerably from that of
      globular proteins implying the role of disordered parts and the significance of
      hydrophobic interactions in the folding of proteins. The shape asymmetry of the
      two classes of disordered proteins is determined by calculating the asphercity
      and shape parameters, derived from the cartesian components of radius of gyration
      tensor. Disordered proteins of group a are more spherical as compared to the
      natively unstructured proteins (group b), which are more prolate. Both groups of
      proteins exhibit similar types of side-chain backbone contacts, as that of the
      globular proteins. While disordered proteins contains few hydrophobic residues
      natively unstructured proteins are characterized by a residues of low mean
      hydrophobicity and high mean net charge.

PMID- 22582808
TI  - Sfrp5 expression and secretion in adipocytes are up-regulated during
      differentiation and are negatively correlated with insulin resistance.
AB  - We have examined the patterns of Sfrp5 (secreted frizzled-related protein 5) mRNA
      expression and protein secretion during adipocyte differentiation, and
      investigated the potential role of Sfrp5 in IR (insulin resistance) in
      adipocytes. 3T3-L1 pre-adipocytes were induced for differentiation, and RT-PCR
      (reverse transcription-PCR) and ELISA assays were used to determine Sfrp5 mRNA
      expression and protein secretion. The results showed that with the
      differentiation and maturity of pre-adipocytes, transcription and protein
      secretion of Sfrp5 gradually increased, peaking on the 9th day of
      differentiation. Sfrp5 mRNA expression in mature adipocytes was decreased by 20,
      22 and 32 upon treatment with dexamethasone, insulin and TNF (tumour necrosis
      factor) respectively, whereas Sfrp5 protein secretion was decreased by 15, 17 and
      30%, correspondingly. In contrast, Sfrp5 mRNA expression in mature adipose was
      increased by 34 and 19% upon treatment with rosiglitazone and metformin
      respectively, whereas Sfrp5 protein secretion was increased by 10 and 6%,
      correspondingly. In conclusion, Sfrp5 mRNA expression and protein secretion
      depend on the differentiation of adipocytes. The dysregulation of Sfrp5
      expression and secretion is directly correlated with IR. Up-regulation of Sfrp5
      expression and secretion in adipocytes may be one crucial mechanism by which
      rosiglitazone and metformin improve insulin sensitivity. 

PMID- 22582809
TI  - Polymer nanofibers embedded with aligned gold nanorods: a new platform for
      plasmonic studies and optical sensing.
AB  - This paper reports the fabrication and characterization of polymer nanofibers
      embedded with gold nanorods in uniaxial alignment for applications in optical
      waveguiding and sensing. Using a waveguiding approach, we demonstrated highly
      efficient excitation of localized surface plasmon resonance in the embedded gold
      nanorods with a photon-to-plasmon-conversion efficiency as high as 70% for a
      single nanorod at its longitudinal resonance wavelength. On the basis of
      waveguiding polymer nanofibers embedded with gold nanorods, we further
      demonstrated compact optical humidity sensors with a response time of 110 ms and
      an operation optical power as low as 500 pW.

PMID- 22582810
TI  - Genome-wide architecture of reproductive isolation in a naturally occurring
      hybrid zone between Mus musculus musculus and M. m. domesticus.
AB  - Studies of a hybrid zone between two house mouse subspecies (Mus musculus
      musculus and M. m. domesticus) along with studies using laboratory crosses reveal
      a large role for the X chromosome and multiple autosomal regions in reproductive
      isolation as a consequence of disrupted epistasis in hybrids. One limitation of
      previous work has been that most of the identified genomic regions have been
      large. The goal here is to detect and characterize precise genomic regions
      underlying reproductive isolation. We surveyed 1401 markers evenly spaced across
      the genome in 679 mice collected from two different transects. Comparisons
      between transects provide a means for identifying common patterns that likely
      reflect intrinsic incompatibilities. We used a genomic cline approach to identify
      patterns that correspond to epistasis. From both transects, we identified
      contiguous regions on the X chromosome in which markers were inferred to be
      involved in epistatic interactions. We then searched for autosomal regions
      showing the same patterns and found they constitute about 5% of autosomal
      markers. We discovered substantial overlap between these candidate regions
      underlying reproductive isolation and QTL for hybrid sterility identified in
      laboratory crosses. Analysis of gene content in these regions suggests a key role
      for several mechanisms, including the regulation of transcription, sexual
      conflict and sexual selection operating at both the postmating prezygotic and
      postzygotic stages of reproductive isolation. Taken together, these results
      indicate that speciation in two recently diverged (c. 0.5 Ma) house mouse
      subspecies is complex, involving many genes dispersed throughout the genome and
      associated with distinct functions.

PMID- 22582811
TI  - Hydrothermal treatment of water yam starch in a non-granular state: slowly
      digestible starch content and structural characteristics.
AB  - Gelatinized water yam starch was subjected to hydrothermal treatment (25, 30, and
      35% moisture content for 1, 8, 16, and 24 h at 100  degrees C) and characterized
      by X-ray diffractometry, solid-state 13C cross-polarization and magic-angle
      spinning nuclear magnetic resonance, differential scanning calorimetry, and
      digestibility analysis. The slowly digestible starch (SDS) content of the starch
      treated at 30% moisture content for 24 h reached 49.1%, 31.9% higher than that of
      the control starch. The B-type pattern of native starch was re-crystallized to
      the A-type by hydrothermal treatment. The SDS content showed negative
      correlations with T(o), T(p), T(c), and T(r), but showed a positive correlation
      with melting enthalpy. Furthermore, SDS was positively correlated with
      hydrothermal reaction time, moisture content, relative crystallinity, and the
      double-helix proportion. The structural changes in hydrothermally treated water
      yam starches resulted in the enhancement of SDS. PRACTICAL APPLICATION: The
      hydrothermally treated water yam starch could be used as a food ingredient for
      slow-energy supply or dietary fiber.

PMID- 22582812
TI  - Relevance of deterministic structures for modeling of transport: the Lauswiesen
      case study.
AB  - Knowledge of site-specific contaminant transport processes is an essential
      requirement for performing various tasks concerning the protection and management
      of groundwater resources. However, prediction of their behavior is often
      difficult, especially in heterogeneous aquifers because of the lack of
      information about flow- and transport-governing subsurface structures and
      parameters. Hence, stochastic approaches have been developed and frequently used.
      However, extensive modeling studies on sedimentary structures have shown that
      consideration of hydrogeological subunits and their distribution can be essential
      for transport modeling. A case study from the intensely investigated Lauswiesen
      site is used to demonstrate that more accurate predictions are possible with
      improved knowledge of deterministic structures. Results of this case study using
      direct-push injection logging (DPIL) provide a more reliable characterization of
      hydraulic conductivity than sieve and flow meter data.

PMID- 22582813
TI  - Predicting response to reassurances and uncertainties in bioterrorism
      communications for urban populations in New York and California.
AB  - Recent national plans for recovery from bioterrorism acts perpetrated in densely
      populated urban areas acknowledge the formidable technical and social challenges
      of consequence management. Effective risk and crisis communication is one
      priority to strengthen the U.S.'s response and resilience. However, several
      notable risk events since September 11, 2001, have revealed vulnerabilities in
      risk/crisis communication strategies and infrastructure of agencies responsible
      for protecting civilian populations. During recovery from a significant
      biocontamination event, 2 goals are essential: (1) effective communication of
      changing risk circumstances and uncertainties related to cleanup, restoration,
      and reoccupancy; and (2) adequate responsiveness to emerging information needs
      and priorities of diverse populations in high-threat, vulnerable locations. This
      telephone survey study explored predictors of public reactions to uncertainty
      communications and reassurances from leaders related to the remediation stage of
      an urban-based bioterrorism incident. African American and Hispanic adults
      (N=320) were randomly sampled from 2 ethnically and socioeconomically diverse
      geographic areas in New York and California assessed as high threat, high
      vulnerability for terrorism and other public health emergencies. Results suggest
      that considerable heterogeneity exists in risk perspectives and information needs
      within certain sociodemographic groups; that success of risk/crisis communication
      during recovery is likely to be uneven; that common assumptions about public
      responsiveness to particular risk communications need further consideration; and
      that communication effectiveness depends partly on preexisting values and risk
      perceptions and prior trust in leaders. Needed improvements in communication
      strategies are possible with recognition of where individuals start as a
      reference point for reasoning about risk information, and comprehension of how
      this influences subsequent interpretation of agencies' actions and
      communications.

PMID- 22582814
TI  - Transfection of hypoxia-inducible factor-1 decoy oligodeoxynucleotides suppresses
      expression of vascular endothelial growth factor in oral squamous cell carcinoma
      cells.
AB  - Vasculature development is thought to be an important aspect in the growth and
      metastasis of solid tumors. Among the many angiogenic factors produced by tumor
      cells, vascular endothelial growth factor (VEGF) is considered to play a key role
      in angiogenic processes. VEGF synthesis is modulated by hypoxia-inducible factor
      1 (HIF-1) function within the hypoxic microenvironment of growing cancer tissue.
      To inhibit HIF-1 activation, oligodeoxynucleotides (ODNs) were synthesized and
      transferred with either the consensus sequence for HIF-1 binding or a mutated
      form of this sequence. If we could transfer a large number of ODNs into the
      cancer cell nucleus, activated HIF-1 might bind to the ODNs, resulting in
      inhibition of hypoxia-induced VEGF synthesis. We transferred these ODNs into
      cultured oral squamous cell carcinoma cells (SAS cells) using the
      hemagglutinating virus of Japan (HVJ)-liposome method. Hypoxia-mediated
      expression of VEGF by cancer cells was suppressed by transfection of HIF-1 decoy
      ODNs, but not by mutated HIF-1 decoy ODNs. HIF-1 decoy ODN transfection also
      inhibited VEGF protein synthesis. These results suggest that transfection with
      HIF-1 decoy ODNs is effective for regulating tumor growth by reducing VEGF.

PMID- 22582815
TI  - Synovial fluid dynamics with small disc perforation in temporomandibular joint.
AB  - The articular disc plays an important role as a stress absorber in joint
      movement, resulting in stress reduction and redistribution in the
      temporomandibular joint (TMJ). The flow of synovial fluid in the TMJ may follow a
      regular pattern during movement of the jaw. We hypothesised that the regular
      pattern is disrupted when the TMJ disc is perforated. By computed tomography
      arthrography, we studied the upper TMJ compartment in patients with small disc
      perforation during jaw opening-closing at positions from 0 to 3 cm. Finite
      element fluid dynamic modelling was accomplished to analyse the pattern of fluid
      flow and pressure distribution during the movements. The results showed that the
      fluid flow in the upper compartment generally formed an anticlockwise circulation
      but with local vortexes with the jaw opening up to 2 cm. However, when the jaw
      opening-closing reached 3 cm, an abnormal flow field and the fluid pressure
      change associated with the perforation may increase the risk of perforation
      expansion or rupture and is unfavourable for self-repair of the perforated disc.

PMID- 22582816
TI  - Choice behavior of pigeons (Columba livia), college students, and preschool
      children (Homo sapiens) in the Monty Hall dilemma.
AB  - In the Monty Hall dilemma, an individual chooses between three options, only one
      of which will deliver a prize. After the initial choice, one of the nonchosen
      options is revealed as a losing option, and the individual can choose to stay
      with the original choice or switch to the other remaining option. Previous
      studies have found that most adults stay with their initial choice, although the
      chances of winning are 2/3 for switching and 1/3 for staying. Pigeons, college
      students, and preschool children were given many trials on this task to examine
      how their choices might change with experience. The college students began to
      switch on a majority of trials much sooner than the pigeons, contrary to the
      findings by Herbranson and Schroeder (2010) that pigeons perform better than
      people on this task. In all three groups, some individuals approximated the
      optimal strategy of switching on every trial, but most did not. Many of the
      preschoolers immediately showed a pattern of always switching or always staying
      and continued this pattern throughout the experiment. In a condition where the
      probability of winning was 90% after a switch, all college students and all but
      one pigeon learned to switch on nearly every trial. The results suggest that one
      main impediment to learning the optimal strategy in the Monty Hall task, even
      after repeated trials, is the difficulty in discriminating the different
      reinforcement probabilities for switching versus staying.

PMID- 22582817
TI  - Long-term retention of visual tasks by two species of emydid turtles, Pseudemys
      nelsoni and Trachemys scripta.
AB  - Long-lived species are expected to have long-term memory capabilities. In this
      study we tested nine Florida Red-bellied Cooters (Pseudemys nelsoni) on their
      retention for both a procedural food acquisition task and visual discrimination
      task learned in a previous experiment. The turtles were tested and retrained
      after two months, after another 7.5 months, and finally after 36 months of no
      interaction with the test apparatus during the intervening periods. Turtles
      retained memory for the choice task and needed little retraining throughout.
      Furthermore, in a different visual discrimination task, both P. nelsoni and
      Trachemys scripta turtles showed 100% retention after 3.5 months of no testing.
      Odor-controlled tests confirmed that turtles were using visual cues to solve the
      task. Thus, in a laboratory context turtles demonstrate long-term memory of
      visual discrimination tasks, which relates to apparent abilities in natural
      environments.

PMID- 22582818
TI  - Cyclic aza-peptide integrin ligand synthesis and biological activity.
AB  - Aza-peptides are obtained by replacement of the alpha-C-atom of one or more amino
      acids by a nitrogen atom in a peptide sequence. Introduction of aza-residues into
      peptide sequences may result in unique structural and pharmacological properties,
      such that aza-scanning may be used to probe structure-activity relationships. In
      this study, a general approach for the synthesis of cyclic aza-peptides was
      developed by modification of strategies for linear aza-peptide synthesis and
      applied in the preparation of cyclic aza-pentapeptides containing the RGD (Arg
      Gly-Asp) sequence. Aza-amino acid scanning was performed on the cyclic RGD
      peptide Cilengitide, cyclo[R-G-D-f-N(Me)V] 1, and its parent peptide cyclo(R-G-D
      f-V) 2, potent antagonists of the alphavbeta3, alphavbeta5, and alpha5beta1
      integrin receptors, which play important roles in human tumor metastasis and
      tumor-induced angiogenesis. Although incorporation of the aza-residues resulted
      generally in a loss of binding affinity, cyclic aza-peptides containing aza
      glycine retained nanomolar activity toward the alphavbeta3 receptor.

PMID- 22582819
TI  - Fast self-assembly kinetics of quantum dots and a dendrimeric peptide ligand.
AB  - Engineered peptide ligands with exceptionally high affinity for metal can self
      assemble with nanoparticles in biological fluids. A high-affinity dendrimeric
      peptide ligand for CdSe-ZnS quantum dots (QDs) exhibited very fast association
      kinetics with QDs and reached equilibrium within 2 s. Here, we have combined a
      droplet-based microfluidic device with fluorescence detection based on Forster
      resonance energy transfer (FRET) to provide subsecond resolution in dissecting
      this fast self-assembly kinetics in solution. This work represents the first
      application of microfluidic devices to ligand-particle assembly for the
      measurement of fast assembly kinetics in solution.

PMID- 22582820
TI  - Detection of copy number variants in the horse genome and examination of their
      association with recurrent laryngeal neuropathy.
AB  - We used the data from a recently performed genome-wide association study using
      the Illumina Equine SNP50 beadchip for the detection of copy number variants
      (CNVs) and examined their association with recurrent laryngeal neuropathy (RLN),
      an important equine upper airway disease compromising performance. A total of
      2797 CNVs were detected for 477 horses, covering 229 kb and seven SNPs on
      average. Overlapping CNVs were merged to define 478 CNV regions (CNVRs). CNVRs,
      particularly deletions, were shown to be significantly depleted in genes. Fifty
      two of the 67 common CNVRs (frequency >= 1%) were validated by association
      mapping, Mendelian inheritance, and/or Mendelian inconsistencies. None of the 67
      common CNVRs were significantly associated with RLN when accounting for multiple
      testing. However, a duplication on chromosome 10 was detected in 10 cases
      (representing three breeds) and two unphenotyped parents but in none of the
      controls. The duplication was embedded in an 8-Mb haplotype shared across breeds.

PMID- 22582821
TI  - Epithelial cells in culture: injured or differentiated cells?
AB  - Isolation of epithelial cells for cell culture is based on destruction of
      epithelial integrity. The consequences are manifold: cell polarity and specific
      cell functions are lost; cells acquire non-epithelial characteristics and start
      to proliferate. This situation may also occur in situ when parts of the
      epithelium are lost, either by apoptosis or necrosis by organ or tissue injury.
      During recovery from this injury, surviving epithelial cells proliferate and may
      restore epithelial integrity and finally re-differentiate into functional
      epithelial cells. In vitro, this re-differentiation is mostly not complete due to
      sub-optimal culture conditions. Therefore cultured epithelial cells resemble
      wounded or injured epithelia rather than healthy and well differentiated
      epithelia. The value of an in vitro cell model is the extent to which it helps to
      understand the function of the cells in situ. A variety of parameters influence
      the state of differentiation of cultured cells in vitro. Although each of these
      parameters had been studied, the picture how they co-ordinately influence the
      state of differentiation of epithelial cells in vitro is incomplete. Therefore we
      discuss the influence of the isolation method and cell culture on epithelial
      cells, and outline strategies to achieve highly differentiated epithelial cells
      for the use as an in vitro model. 

PMID- 22582822
TI  - Comment on: what goes between the name and the thing: should we rethink VEGF
      denomination in preeclampsia?

PMID- 22582823
TI  - Oil spill environmental forensics: the Hebei Spirit oil spill case.
AB  - After the Hebei Spirit oil spill (HSOS) in December 2007, mixtures of three types
      of Middle East crude oil (total 12,547 kL) were stranded along 375 km of
      coastline in Western Korea. Emergency responses together with 1.3 million
      volunteers' activity rapidly removed ca. 20% of spilled oil but the lingering
      oils have been found along the heavily impacted shorelines for more than 4 years.
      The HSOS was the worst oil spill case in Republic of Korea, and there were many
      issues and lessons to be shared. In this study, we summarized some of the oil
      spill environmental forensic issues that were raised after the HSOS. Rapid
      screening using on-site measurement, long-term monitoring of multimedia,
      fingerprinting challenges and evaluation of the extent of the submerged oil were
      introduced, which supported decision making process of oil spill cleanup,
      mitigation of debates among stakeholders and provided scientific backgrounds for
      reasonable compensation.

PMID- 22582824
TI  - Bi-directional regulation of CaMKIIalpha phosphorylation at Thr286 by NMDA
      receptors in cultured cortical neurons.
AB  - The N-methyl-D-aspartate (NMDA) receptor (NMDAR)-stimulated autophosphorylation
      of calmodulin-dependent kinase IIalpha at Thr286 may regulate many aspects of
      neuroplasticity. Here, we show that low NMDA concentration (20 MUM) up-regulated
      Thr286 phosphorylation, and high concentration (100 MUM) caused
      dephosphorylation. We next modulated the strength of NMDAR activation by
      manipulating NMDAR 2A subunit (NR2A) and NMDAR 2B subunit (NR2B), which represent
      the major NMDAR subtypes in forebrain regions. Pharmacological inhibition and
      molecular knockdown of NR2A or NR2B blocked 20 MUM NMDA-induced phosphorylation.
      Conversely, over-expression of NR2A or NR2B enhanced phosphorylation by 20 MUM
      NMDA. The 100 MUM NMDA-induced dephosphorylation was suppressed by inhibition or
      knockdown of NR2A or NR2B, and enhanced by over-expression of NR2A or NR2B.
      Compared to NR2A, NR2B showed a higher impact on the NMDA-stimulated bi
      directional regulation of Thr286 phosphorylation. We further found that
      activation of NR2A and NR2B by 100 MUM NMDA-induced dephosphorylation through
      protein phosphatases (PP) that are inhibited by high concentration okadaic acid
      (1 MUM), but not by PP2A and PP2B inhibitors. This novel function of NMDAR in
      dynamic regulation of calmodulin-dependent kinase IIalpha activity provides new
      evidence to support the current understanding that, depending on the degree of
      activation, NMDAR may lead to different and even opposing effects on
      intracellular signaling.

PMID- 22582827
TI  - New glycosidic alkaloid from the nearly ripe fruits of Euodia rutaecarpa.
AB  - A new natural product, 10-hydroxyrutaecarpine (1), and a rarely new glycosidic
      alkaloid, rutaecarpine-10-O-rutinoside (2), along with the known compounds
      rutaecarpine (3), evodiamine, wuzhuyuamide-I, and dehydroevodiamine were isolated
      from the butanol fraction of 70% ethanol aqueous extract of the dried and nearly
      ripe fruits of Euodia rutaecarpa (Juss.) Benth. Their structures were elucidated
      on the basis of their spectroscopic data.

PMID- 22582825
TI  - Intrinsic energy landscapes of amino acid side-chains.
AB  - Amino acid side-chain conformational properties influence the overall structural
      and dynamic properties of proteins and, therefore, their biological functions. In
      this study, quantum mechanical (QM) potential energy surfaces for the rotation of
      side-chain chi(1) and chi(2) torsions in dipeptides in the alphaR, beta, and
      alphaL backbone conformations were calculated. The QM energy surfaces provide a
      broad view of the intrinsic conformational properties of each amino acid side
      chain. The extent to which intrinsic energetics dictates side-chain orientation
      was studied through comparisons of the QM energy surfaces with chi(1) and chi(2)
      free energy surfaces from probability distributions obtained from a survey of
      high resolution crystal structures. In general, the survey probability maxima are
      centered in minima of the QM surfaces as expected for sp(3) (or sp(2) for chi(2)
      of Asn, Phe, Trp, and Tyr) atom centers with strong variations between amino
      acids occurring in the energies of the minima indicating intrinsic differences in
      rotamer preferences. High correlations between the QM and survey data were found
      for hydrophobic side-chains except Met, suggesting minimal influence of the
      protein and solution environments on their conformational distributions.
      Conversely, low correlations for polar or charged side-chains indicate a dominant
      role of the environment in stabilizing conformations that are not intrinsically
      favored. Data also link the presence of off-rotamers in His and Trp to favorable
      interactions with the backbone. Results also suggest that the intrinsic
      energetics of the side-chains of Phe and Tyr may play important roles in protein
      folding and stability. Analyses on whether intrinsic side-chain energetics can
      influence backbone preference identified a strong correlation for residues in the
      alphaL backbone conformation. It is suggested that this correlation reflects the
      intrinsic instability of the alphaL backbone such that assumption of this
      backbone conformation is facilitated by intrinsically favorable side-chain
      conformations. Together our results offer a broad overview of the conformational
      properties of amino acid side-chains and the QM data may be used as target data
      for force field optimization.

PMID- 22582826
TI  - Fluence rate-dependent photobleaching of intratumorally administered Pc 4 does
      not predict tumor growth delay.
AB  - We examined effects of fluence rate on the photobleaching of the photosensitizer
      Pc 4 during photodynamic therapy (PDT) and the relationship between
      photobleaching and tumor response to PDT. BALB/c mice with intradermal EMT6
      tumors were given 0.03 mg kg(-1) Pc 4 by intratumor injection and irradiated at
      667 nm with an irradiance of 50 or 150 mW cm(-2) to a fluence of 100 J cm(-2).
      While no cures were attained, significant tumor growth delay was demonstrated at
      both irradiances compared with drug-only controls. There was no significant
      difference in tumor responses to these two irradiances (P = 0.857). Fluorescence
      spectroscopy was used to monitor the bleaching of Pc 4 during irradiation, with
      more rapid bleaching with respect to fluence shown at the higher irradiance. No
      significant correlation was found between fluorescence photobleaching and tumor
      regrowth for the data interpreted as a whole. Within each treatment group, weak
      associations between photobleaching and outcome were observed. In the 50 mW cm(
      2) group, enhanced photobleaching was associated with prolonged growth delay (P =
      0.188), while at 150 mW cm(-2) this trend was reversed (P = 0.308). Thus, it
      appears that Pc 4 photobleaching is not a strong predictor of individual tumor
      response to Pc 4-PDT under these treatment conditions.

PMID- 22582828
TI  - Chemical vapor deposition-derived graphene with electrical performance of
      exfoliated graphene.
AB  - While chemical vapor deposition (CVD) promises a scalable method to produce large
      area graphene, CVD-grown graphene has heretofore exhibited inferior electronic
      properties in comparison with exfoliated samples. Here we test the electrical
      transport properties of CVD-grown graphene in which two important sources of
      disorder, namely grain boundaries and processing-induced contamination, are
      substantially reduced. We grow CVD graphene with grain sizes up to 250 MUm to
      abate grain boundaries, and we transfer graphene utilizing a novel, dry-transfer
      method to minimize chemical contamination. We fabricate devices on both silicon
      dioxide and hexagonal boron nitride (h-BN) dielectrics to probe the effects of
      substrate-induced disorder. On both substrate types, the large-grain CVD graphene
      samples are comparable in quality to the best reported exfoliated samples, as
      determined by low-temperature electrical transport and magnetotransport
      measurements. Small-grain samples exhibit much greater variation in quality and
      inferior performance by multiple measures, even in samples exhibiting high field
      effect mobility. These results confirm the possibility of achieving high
      performance graphene devices based on a scalable synthesis process.

PMID- 22582829
TI  - Cultivation shapes genetic novelty in a globally important invader.
AB  - Acacia saligna is a species complex that has become invasive in a number of
      countries worldwide where it has caused substantial environmental and economic
      impacts. Understanding genetic and other factors contributing to its success may
      allow managers to limit future invasions of closely related species. We used
      three molecular markers to compare the introduced range (South Africa) to the
      native range (Western Australia). Nuclear markers showed that invasive
      populations are divergent from native populations and most closely related to a
      cultivated population in Western Australia. We also found incongruence between
      nuclear and chloroplast data that, together with the long history of cultivation
      of the species, suggest that introgressive hybridization (coupled with
      chloroplast capture) may have occurred within A. saligna. While we could not
      definitively prove introgression, the genetic distance between cultivated and
      native A. saligna populations was comparable to known interspecific divergences
      among other Acacia species. Therefore, cultivation, multiple large-scale
      introductions and possibly introgressive hybridization have rapidly given rise to
      the divergent genetic entity present in South Africa. This may explain the known
      global variation in invasiveness and inaccuracy of native bioclimatic models in
      predicting potential distributions.

PMID- 22582830
TI  - Long-time correlations and hydrophobe-modified hydrogen-bonding dynamics in
      hydrophobic hydration.
AB  - The physical mechanisms behind hydrophobic hydration have been debated for over
      65 years. Spectroscopic techniques have the ability to probe the dynamics of
      water in increasing detail, but many fundamental issues remain controversial. We
      have performed systematic first-principles ab initio Car-Parrinello molecular
      dynamics simulations over a broad temperature range and provide a detailed
      microscopic view on the dynamics of hydration water around a hydrophobic
      molecule, tetramethylurea. Our simulations provide a unifying view and resolve
      some of the controversies concerning femtosecond-infrared, THz-GHz dielectric
      relaxation, and nuclear magnetic resonance experiments and classical molecular
      dynamics simulations. Our computational results are in good quantitative
      agreement with experiments, and we provide a physical picture of the long-debated
      "iceberg" model; we show that the slow, long-time component is present within the
      hydration shell and that molecular jumps and over-coordination play important
      roles. We show that the structure and dynamics of hydration water around an
      organic molecule are non-uniform.

PMID- 22582832
TI  - The effect of food bolus location on jaw movement smoothness and masticatory
      efficiency.
AB  - Masticatory efficiency in individuals with extensive tooth loss has been widely
      discussed. However, little is known about jaw movement smoothness during chewing
      and the effect of differences in food bolus location on movement smoothness and
      masticatory efficiency. The aim of this study was to determine whether
      experimental differences in food bolus location (anterior versus posterior) had
      an effect on masticatory efficiency and jaw movement smoothness. Jaw movement
      smoothness was evaluated by measuring jerk-cost (calculated from acceleration)
      with an accelerometer that was attached to the skin of the mentum of 10
      asymptomatic subjects, and acceleration was recorded during chewing on two-colour
      chewing gum, which was used to assessed masticatory efficiency. Chewing was
      performed under two conditions: posterior chewing (chewing on molars and
      premolars only) and anterior chewing (chewing on canine and first premolar teeth
      only). Jerk-cost and masticatory efficiency (calculated as the ratio of unmixed
      azure colour to the total area of gum, the unmixed fraction) were compared
      between anterior and posterior chewing with the Wilcoxon signed rank test (two
      tailed). Subjects chewed significantly less efficiently during anterior chewing
      than during posterior chewing (P = 0.0051). There was no significant difference
      in jerk-cost between anterior and posterior conditions in the opening phase (P =
      0.25), or closing phase (P = 0.42). This is the first characterisation of the
      effect of food bolus location on jaw movement smoothness at the same time as
      recording masticatory efficiency. The data suggest that anterior chewing
      decreases masticatory efficiency, but does not influence jerk-cost.

PMID- 22582831
TI  - Utilizing afterglow magnetization from cross-polarization magic-angle-spinning
      solid-state NMR spectroscopy to obtain simultaneous heteronuclear
      multidimensional spectra.
AB  - The time required for data acquisition and subsequent spectral assignment are
      limiting factors for determining biomolecular structure and dynamics using solid
      state NMR spectroscopy. While strong magnetic dipolar couplings give rise to
      relatively broad spectra lines, the couplings also mediate the coherent
      magnetization transfer via the Hartmann-Hahn cross-polarization (HH-CP)
      experiment. This mechanism is used in nearly all backbone assignment experiments
      for carrying out polarization transfer between (1)H, (15)N, and (13)C. In this
      Article, we describe a general spectroscopic approach to use the residual or
      "afterglow" magnetization from the (15)N to (13)C selective HH-CP experiment to
      collect a second multidimensional heteronuclear data set. This approach allowed
      for the collection of two commonly used sequential assignment experiments (2D NCA
      and NCO or 3D NCACX and NCOCX) at the same time. Our "afterglow" technique was
      demonstrated with uniformly [(13)C,(15)N] and [1,3-(13)C] glycerol-labeled
      ubiquitin using instrumentation available on all standard solid-state NMR
      spectrometers configured for magic-angle-spinning. This method is compatible with
      several other sensitivity enhancement experiments and can be used as an isotopic
      filtering tool to reduce the spectral complexity and decrease the time needed for
      assignment.

PMID- 22582833
TI  - Moderating effects of teacher-student relationship in adolescent trajectories of
      emotional and behavioral adjustment.
AB  - This study examined relations between effortful control, parent-adolescent
      conflict, and teacher-student relationships and the concurrent and longitudinal
      impact of these factors on adolescent depression and misconduct. In particular,
      we examined whether the risks of low effortful control and parent-adolescent
      conflict could be buffered by positive teacher-student relationships
      characterized by warmth and trust. Data were collected on 1,400 urban youths (52%
      female, 51% Black, 44% White) who reported on their effortful control at age 13
      years and on their depressive symptoms and misconduct from ages 13-18. Teacher
      student relationship data were collected from teacher-report at age 13 and parent
      adolescent conflict data from parent-report at age 13. As hypothesized,
      regardless of gender, both early poor effortful control and conflictive parent
      adolescent relationship were general risks for adolescents' depression and
      misconduct. Positive teacher-student relationships protected adolescents against
      depression and misconduct throughout ages 13-18. In addition, positive teacher
      student relationships moderated the negative influences of adolescents' early
      poor effortful control and conflictive parent-adolescent relationships on
      misconduct and helped such at-risk adolescents to attain less behaviorally
      delinquent developmental trajectories over time.

PMID- 22582834
TI  - Trajectories of attentional development: an exploration with the master
      activation map model.
AB  - The developmental trajectories of several attention components, such as
      orienting, inhibition, and the guidance of selection by relevance (i.e., advance
      knowledge relevant to the task) were investigated in 498 participants (ages 7, 8,
      9, 10, 11, and 20). The paradigm was based on Michael et al.'s (2006) master
      activation map model and consisted of 3 visual search tasks presented in an
      intrasubject Latin square design and differing in terms of the probability with
      which a salient signal was associated with the target or a distractor. The
      results suggest that, whereas computations of salience were already proficient at
      age 7, and the use of advance knowledge was efficient throughout childhood,
      albeit without reaching adult levels, the integration of salience and relevance
      reached its asymptotic level at age 8. Although moving and engaging attention was
      proficient at age 7, disengaging attention started to improve at age 9, reaching
      its adult level at age 11. As regards inhibition of salient distractors, the
      authors found no developmental pattern before adulthood, regardless of whether
      advance knowledge was available about the distractor or not, although all
      participants were able to use such knowledge to reduce overall interference.
      Finally, some results suggest that the control of resources for strengthening
      inhibition becomes efficient between ages 9 and 10. The developmental
      trajectories were compared with the existing literature and discussed.

PMID- 22582835
TI  - Asymmetric aldol reaction catalyzed by the anion of an ionic liquid.
AB  - Herein we report the synthesis of a chiral imidazolium salt derived from trans-L
      hydroxyproline and its applications as a catalyst for the asymmetric aldol
      reaction. By performing the aldol reaction in [Bmim]NTf(2) as a solvent, we
      report excellent isolated yields of the aldol product (up to 99%), as well as
      modest to excellent selectivities (dr superior to 99:1. ee up to 89%).
      Mechanistic insights and the origins of the selectivity of the aldol reaction are
      discussed on the basis of the results obtained with two catalytic imidazolium
      salts having different H-bonding potential.

PMID- 22582837
TI  - Gene polymorphism of interleukin-1 alpha and beta in keratocystic odontogenic
      tumors.
AB  - AIM AND BACKGROUND: Odontogenic keratocysts have a different growth mechanism and
      biologic behavior in comparison with more common dentigerous and radicular cysts.
      It was reclassified as keratocystic odontogenic tumor (KCOT). The proliferative
      activity of the epithelial cells of KCOT has a close relationship with tissue
      levels of interleukin-1 (IL-1). Moreover, IL-1 increases the expression of
      several matrix metalloproteinases in the fibroblasts of adjacent stroma and
      activates the osteoclastogenesis process. So it plays an important role in the
      activity, spread, and local aggressiveness of this tumor. Therefore, it seems
      that the gene polymorphism of the cytokines of the IL-1 family is influential in
      the pathogenesis of KCOT and the patients' susceptibility to disease. METHOD: A
      total of 38 blood samples of patients suffering from KCOT and 150 blood samples
      of healthy patients were assessed using PCR-SSP. The blood samples were assessed
      for the following polymorphisms: interleukin-1 alpha (-889) and interleukin-1
      beta (-511). Following up the patients, we found six recurrent and one syndromic
      cases. FINDINGS: By comparing the case and control groups, we observed the
      significant dominance of allele T over C, and genotype TT over CC and CT in IL
      1alpha, although no significant difference was seen in the allele frequency and
      genotypes regarding IL-1beta. CONCLUSION: The function of IL-1alpha has a
      significant relationship with KCOT. Its effective genotype associated with
      pathogenesis, growth, local invasion, and recurrence is TT.

PMID- 22582838
TI  - Surfactant-mediated electrodeposition of bismuth telluride films and its effect
      on microstructural properties.
AB  - We report the synthesis of highly crystallographically textured films of
      stoichiometric bismuth telluride (Bi(2)Te(3)) in the presence of a surfactant,
      sodium lignosulfonate (SL), that resulted in the improved alignment of films in
      the (110) plane and offered good control over the morphology and roughness of the
      electrodeposited films. SL concentrations in the range 60-80 mg dm(-3) at a
      deposition potential of -0.1 V vs SCE (saturated calomel electrode) were found to
      yield the most improved crystallinity and similar or superior thermoelectric
      properties compared with results reported in the literature.

PMID- 22582839
TI  - Commentary: combination therapy with two nucleos(t)ide analogues in chronic
      hepatitis B.

PMID- 22582840
TI  - Letter: rising incidence of obesity in the coeliac population - a malady or
      maladaptation?

PMID- 22582841
TI  - Letter: third-line rescue therapy with levofloxacin after failure of two
      treatments to eradicate Helicobacter pylori infection.

PMID- 22582844
TI  - Cathepsin H functions as an aminopeptidase in secretory vesicles for production
      of enkephalin and galanin peptide neurotransmitters.
AB  - Peptide neurotransmitters function as key intercellular signaling molecules in
      the nervous system. These peptides are generated in secretory vesicles from
      proneuropeptides by proteolytic processing at dibasic residues, followed by
      removal of N- and/or C-terminal basic residues to form active peptides.
      Enkephalin biosynthesis from proenkephalin utilizes the cysteine protease
      cathepsin L and the subtilisin-like prohormone convertase 2 (PC2). Cathepsin L
      generates peptide intermediates with N-terminal basic residue extensions, which
      must be removed by an aminopeptidase. In this study, we identified cathepsin H as
      an aminopeptidase in secretory vesicles that produces (Met)enkephalin (ME) by
      sequential removal of basic residues from KR-ME and KK-ME, supported by in vivo
      knockout of the cathepsin H gene. Localization of cathepsin H in secretory
      vesicles was demonstrated by immunoelectron microscopy and immunofluorescence
      deconvolution microscopy. Purified human cathepsin H sequentially removes N
      terminal basic residues to generate ME, with peptide products characterized by
      nano-LC-MS/MS tandem mass spectrometry. Cathepsin H shows highest activities for
      cleaving N-terminal basic residues (Arg and Lys) among amino acid fluorogenic
      substrates. Notably, knockout of the cathepsin H gene results in reduction of ME
      in mouse brain. Cathepsin H deficient mice also show a substantial decrease in
      galanin peptide neurotransmitter levels in brain. These results illustrate a role
      for cathepsin H as an aminopeptidase for enkephalin and galanin peptide
      neurotransmitter production.

PMID- 22582845
TI  - The low level laser therapy effect on the remodeling of bone extracellular
      matrix.
AB  - The low level laser therapy (LLLT) has been used as an option to accelerate the
      regeneration of bone tissue. In this study, both femurs of male Wistar rats (30
      animals) were injured with a drill and the effect of LLLT using a laser diode
      (100 mW at 660 nm) in the bone matrix on the left paw measured. LLLT effect on
      the healing bone tissue matrix was evaluated by a combination of
      immunohistochemical histomorphometry, confocal immunofluorescence microscopy and
      isolation and characterization of glycosaminoglycans. Histomorphometric analysis
      showed that LLLT increased bone matrix and showing more organized. Alcian Blue
      and PAS staining seems to suggest differential glycosaminoglycans and
      glycoproteins. The data showed increased expression of chondroitin sulfate and
      hyaluronic acid, after reduction as the LLLT and mature bone, resembling the
      expression of osteonectin and biglycan. The difference in expression of siblings
      (DMP-1, OPN and BSP) is in accordance with the repair accelerated bone formation
      after the application of LLLT as compared with control. The expression of
      osteonectin and osteocalcin supports their role in bone mineralization protein,
      indicating that LLLT accelerates this process. The overall data show that LLLT
      bone changes dynamic array, shortening the time period involved in the bone
      repair.

PMID- 22582846
TI  - Salivary flow rate and risk of malnutrition - a study among dentate, community
      dwelling older people.
AB  - OBJECTIVE: To analyse the relation between unstimulated and stimulated salivary
      secretion and the risk of malnutrition among home-dwelling elderly people.
      BACKGROUND: Saliva has an important role in eating. Despite this, there are only
      a few studies on the role of salivary secretion in the development of
      malnutrition among elderly people. MATERIALS AND METHODS: The study population
      consisted of 157 subjects aged 75 or older. This was a part of GeMS study carried
      out in Kuopio, in eastern Finland. The data used in this study were collected by
      means of interviews and geriatric and oral clinical examinations. The risk of
      malnutrition was measured using the Mini Nutritional Assessment Short-Form.
      Logistic regression models were used to estimate odds ratios (OR) and their 95%
      Confidence Intervals (CI). RESULTS: Subjects with a low unstimulated salivary
      flow rate (<0.1 ml/min) or stimulated salivary flow rate (<1.0 ml/min) had no
      statistically significant increase in risk of malnutrition, OR: 1.3, CI: 0.5-3.9,
      OR: 1.5, CI: 0.5-4.2, respectively, when compared with those with a normal
      unstimulated and stimulated salivary flow rate. CONCLUSION: Our results do not
      support the concept that low salivary secretion is an important risk factor for
      malnutrition among community-dwelling elders.

PMID- 22582847
TI  - Use of the King's Outcome Scale for Childhood Head Injury in the evaluation of
      outcome in childhood traumatic brain injury.
AB  - OBJECTIVE: To examine the inter-rater reliability of The King's Outcome Scale for
      Childhood Head Injury (KOSCHI) with clinicians of varying experience in
      paediatric traumatic brain injury (TBI); and to examine change in outcome during
      long-term follow-up of children following traumatic brain injury (TBI) using
      KOSCHI. METHOD: Retrospective assessment of detailed clinic reports of 97
      children followed-up by a tertiary specialist paediatric brain injury service.
      Investigators were blinded to each other's scores. RESULTS: Inter-rater
      reliability was substantial (weighted kappa 0.71) and similar for investigators
      of varying experience. KOSCHI outcome was strongly associated with markers of
      injury severity (p = 0.028). In longitudinal follow-up, KOSCHI score worsened in
      7 (23%) children who were injured under 8 years but in no older children (p =
      0.02). CONCLUSION: KOSCHI has high inter-rater reliability for investigators of
      different experience. Long-term KOSCHI outcome is associated with injury
      severity. Some young children may develop worse disability over time.

PMID- 22582848
TI  - Repetitive/restricted behaviours and interests in children with cerebral palsy
      and autism spectrum disorder.
AB  - OBJECTIVE: To inspect the presence and severity of deficits in restricted and/or
      repetitive behaviours and interests (RRBIs) in children with cerebral palsy (CP)
      and autism spectrum disorders (ASDs). METHODS: Children studied (18-35 months of
      age) belonged to one of three diagnostic groups: children with CP and autism (n =
      11), children with CP and Pervasive Developmental Disorder-Not Otherwise
      Specified (PDD-NOS; n = 10) and children with a sole diagnosis of CP (n = 15). A
      one-way, between subjects ANOVA was conducted on the Repetitive
      Behaviour/Restricted Interests domain of the Baby and Infant Screen for aUtIsm
      Traits-Part 1 (BISCUIT-Part 1) and followed up with post-hoc tests. Percentage
      endorsements were also calculated for each item of this domain. RESULTS: Children
      with CP + autism had significantly greater impairment. No significant differences
      were found between the CP + PDD-NOS and the CP alone groups. CONCLUSION: The
      implications of these findings are discussed.

PMID- 22582849
TI  - DSM-IV vs DSM-5 diagnostic criteria for toddlers with autism.
AB  - PURPOSE: To evaluate prevalence rates of autism and autism symptomatology in
      toddlers using DSM-IV vs DSM-5 criteria. METHOD: Two thousand seven hundred and
      twenty-one toddlers at risk for a developmental disability participated. DSM-IV
      and DSM-5 criteria were applied and overall prevalence using each set of criteria
      was established. Groups were also compared on BISCUIT-Part 1 scores to determine
      if groups differed on autism symptomatology. RESULTS: DSM-5 resulted in 47.79%
      fewer toddlers being diagnosed with ASD compared to those on the DSM-IV. Toddlers
      diagnosed according to DSM-5 exhibited greater levels of autism symptomatology
      than those diagnosed with DSM-IV, but the latter group still exhibited
      significant levels of autism symptomatology. CONCLUSION: The proposed DSM-5 will
      result in far fewer persons being diagnosed with ASD. These results replicate
      findings from two previous studies, with older children/adolescents and adults.
      As a result of these new criteria, far fewer people will qualify for needed
      autism services.

PMID- 22582850
TI  - From my perspective--perceived participation in mainstream schools in students
      with autism spectrum conditions.
AB  - OBJECTIVES: To examine perceived participation in students with ASC and their
      classmates in mainstream schools and to investigate correlations between
      activities the students wanted to do and actually participated in. METHODS:
      Twenty-two students with ASC and their 382 classmates responded to a 46-item
      questionnaire regarding perceived participation in mainstream schools. RESULTS:
      On 57% of the items, students with ASC perceived lower participation than their
      classmates. These results emphasize the importance of knowledge about students'
      perceived participation. However, positive correlations between what the students
      wanted to do and actually did indicate that students with ASC may be
      participating to the extent that they wanted. CONCLUSION: Students with ASC
      perceived lower overall participation in mainstream school than their classmates.
      The correlations between "I want to" and "I do" statements in students with ASC
      indicated that aspects of autonomy are important to incorporate when studying,
      and interpreting, self-rated participation in mainstream schools.

PMID- 22582851
TI  - Validation of the relation between the type and amount of seating support
      provided and Level of Sitting Scale (LSS) scores for children with neuromotor
      disorders.
AB  - OBJECTIVES: To assess the construct validity of the Level of Sitting Scale (LSS)
      by examining the relationship between LSS scores and the type and amount of
      seating supports. METHODS: Secondary analysis of the data for 114 children <=18
      years, with neuromotor disorders who participated in a responsiveness study of
      the Seated Postural Control Measure. RESULTS: A significant inverse relationship
      (Spearman rho = -0.42, p < 0.05) was found between LSS scores and amount of
      seating support provided. Statistically significant differences were also
      revealed between LSS levels of sitting ability (p < 0.004) and pelvic, thigh,
      trunk and head seating components and type of seating system, using Kruskal
      Wallis test. CONCLUSION: This study provides evidence of construct validity for
      the LSS in use as a discriminative measure of sitting ability in children with
      neuromotor disorders. Further validation is justified. Clinically intuitive
      associations between sitting ability and seating interventions were confirmed.

PMID- 22582852
TI  - Technology-based programs to support forms of leisure engagement and
      communication for persons with multiple disabilities: two single-case studies.
AB  - OBJECTIVE: To extend the assessment of technology-based programs for promoting
      stimulus choice and staff/caregiver calls or radio operation and text messaging.
      METHOD: In Study I, the program involved a portable computer, commercial
      software, and a microswitch to allow a man with motor impairment and moderate
      intellectual disability to choose among preferred stimuli (e.g., songs and film
      clips) and persons to call. In Study II, the programs involved (a) a radio device
      and an electronic control unit or (b) a net-book computer and a global system for
      mobile communication. A woman with blindness and moderate intellectual disability
      used a microswitch to operate the radio or send and listen to text messages.
      RESULTS: The participants succeeded in using the technology-aided programs
      through simple microswitch activations involving partial hand closure (Study I)
      or hand pressure (Study II). CONCLUSION: Technology-based programs can provide
      persons with multiple disabilities relevant leisure and communication
      opportunities.

PMID- 22582853
TI  - Parent goals as outcome measures for children receiving treadmill training: a
      series of case reports.
AB  - BACKGROUND: This series of case reports examined attainment of parents' goals for
      children receiving treadmill training and parents' satisfaction with goal
      attainment. METHODS: Four children with cerebral palsy completed 5-8 weeks of
      standardized training while wearing a body weight support harness. Outcome
      measures were family goals using goal attainment scaling (GAS): a score of 0
      equaled goal attainment, scores of -2 and -1 represented lower-than-expected
      performance and +1 and +2 exceeded expected performance. Parent satisfaction with
      goal attainment was assessed on a Likert scale from 1 (very satisfied) to 5 (very
      unsatisfied). RESULTS: All participants achieved GAS levels of >=0, indicating
      all goals were met. All parents rated their satisfaction with goal attainment as
      'very satisfied'. CONCLUSION: This is the first report using family goals as
      outcome measures to assess effects of treadmill training. Future studies of
      treadmill training should include family- and child-centred goals as potential
      outcomes.

PMID- 22582854
TI  - Treatment of PTSD in people with severe intellectual disabilities: a case series.
AB  - OBJECTIVE: There is a dearth of information regarding the treatment of PTSD in
      people with severe intellectual disabilities (ID). The purpose of the present
      case studies was to assess the applicability and effects of an evidence-based
      treatment method for psychological trauma with this population. METHODS: The
      treatment of four single cases with Eye Movement Desensitization and Reprocessing
      (EMDR) was evaluated. Participants included adults and children with a variety of
      symptoms, as well as different histories of negative life events. RESULTS: In all
      cases PTSD symptoms decreased. In all but one case, the gains were maintained at
      15.5 months to 2.5 years following treatment. Depressive symptoms and physical
      complaints diminished and social and adaptive skills improved. CONCLUSION: EMDR
      seems to be an applicable treatment method for clients with severe ID. Reduction
      and maintenance of PTSD symptoms in individuals with severe ID appears to be both
      desirable and obtainable.

PMID- 22582855
TI  - The psychiatric phenotype in triple X syndrome: new hypotheses illustrated in two
      cases.
AB  - BACKGROUND: Triple X syndrome (47,XXX or trisomy X) is a relatively frequent
      cytogenetic condition with a large variety of physical and behavioural
      phenotypes. METHOD: Two adult patients with a triple X karyotype are described.
      RESULTS: Their karyotype was unknown until some years ago. What these patients
      have in common is that they were diagnosed with a broader autism phenotype, they
      were sexually abused, they suffer from psychotic illness and they show
      challenging behaviour, suicidality and a decline in occupational capacity.
      DISCUSSION: These gene-environment interactions are discussed. Gene-environment
      interactions may explain the variety of behavioural and psychiatric phenotypes in
      triple X syndrome. Ongoing atypical development in adults is hypothesized.
      CONCLUSIONS: Gene-environment interactions and ongoing atypical development in
      adults should be taken into account in research concerning the psychiatric
      phenotype of developmental disorders, especially those involving triple X
      syndrome.

PMID- 22582856
TI  - Humin as an electron mediator for microbial reductive dehalogenation.
AB  - We report that humins extracted as the solid fractions from paddy soils or
      sediment are involved in extracellular electron transfer, coupled with microbial
      reductive dehalogenation of pentachlorophenol (PCP), by serving as both electron
      acceptor and electron donor. In our system, humin is requisite for the
      dechlorination of PCP, and this activity cannot be maintained when humin is
      replaced with soluble humic substances or related compounds, including 0.1 M NaOH
      extracted humic acid from soil, Aldrich humic acid, and anthraquinone-2,6
      disulfonate. The function of humins is stable against treatments with H(2)O(2)
      (30%, 30 min), HCl (0.1 M, 48 h), NH(2)OH . HCl (0.1 M, 48 h), NaBH(4) (0.1 M, 15
      h), and heat (121  degrees C, 30 min). Cyclic voltammograms indicated that humin
      harbors redox-active moieties, and electron spin resonance suggested that quinone
      moieties within humin are the redox-active centers. Fourier-transform infrared
      and nuclear magnetic resonance analyses verified the presence of the aryl
      carbonyl carbon group in humin. Although the proportion of redox-active carbon is
      very small, the potential electron-mediating ability is not negligible. The
      finding that humin, in solid form, is redox active has important implications for
      in situ bioremediation, given the wide distribution of humin and the diversity
      and ubiquity of humic substance-utilizing microorganisms.

PMID- 22582857
TI  - Expression of the chaplin and rodlin hydrophobic sheath proteins in Streptomyces
      venezuelae is controlled by sigma(BldN)  and a cognate anti-sigma factor, RsbN.
AB  - The chaplin and rodlin proteins together constitute the major components of the
      hydrophobic sheath that coats the aerial hyphae and spores in Streptomyces, and
      mutants lacking the chaplins are unable to erect aerial hyphae and differentiate
      on minimal media. We have gained insight into the developmental regulation of the
      chaplin (chp) and rodlin (rdl) genes by exploiting a new model species,
      Streptomyces venezuelae, which sporulates in liquid culture. Using microarrays,
      the chaplin and rodlin genes were found to be highly induced during submerged
      sporulation in a bldN-dependent manner. Using sigma(BldN)  ChIP-chip, we show
      that this dependence arises because the chaplin and rodlin genes are direct
      biochemical targets of sigma(BldN) . sven3186 (here named rsbN for regulator of
      sigma BldN), the gene lying immediately downstream of bldN, was also identified
      as a target of sigma(BldN) . Disruption of rsbN causes precocious sporulation and
      biochemical experiments demonstrate that RsbN functions as a sigma(BldN) 
      specific anti-sigma factor.

PMID- 22582858
TI  - Reactions of deprotonated tyrosine and tryptophan with electronically excited
      singlet molecular oxygen (a1Delta(g)): a guided-ion-beam scattering, statistical
      modeling, and trajectory study.
AB  - The reactions of deprotonated tyrosine ([Tyr-H](-)) and tryptophan ([Trp-H](-))
      with the lowest electronically excited state of molecular oxygen
      O(2)[a(1)Delta(g)] have been studied in the gas phase, including the measurement
      of the effects of collision energy (E(col)) on reaction cross sections over a
      center-of-mass E(col) range from 0.05 to 1.0 eV. [Tyr-H](-) and [Trp-H](-) were
      generated using electrospray ionization, and both have a pure carboxylate anion
      structure in the gas phase. Density functional theory calculations and RRKM
      modeling were used to examine properties of various complexes, transition states,
      and products that might be important along the reaction coordinate. It was found
      that deprotonation of Tyr and Trp results in a large effect on their (1)O(2)
      mediated oxidation. For [Tyr-H](-), the reaction corresponds to the formation of
      a hydroperoxide intermediate, followed by intramolecular H transfer and
      subsequent dissociation to product ion 4-(2-aminovinyl)phenolate, and neutral
      H(2)O(2) and CO(2). Despite that the reaction is 1.83 eV exothermic, the reaction
      cross section shows a threshold-like behavior at low E(col) and increases with
      increasing E(col), suggesting that the reaction bears an activation barrier above
      the reactants. Quasi-classical, direct dynamics trajectory simulations were
      carried out for [Tyr-H](-) + (1)O(2) at E(col) = 0.75 eV, using B3LYP/4-31G*
      level of theory. Trajectories demonstrated the intermediacy of complexes at the
      early stage of the reaction. A similar product channel was observed in the
      reaction of [Trp-H](-) with (1)O(2), yielding product ion 3-(2-aminovinyl)indol-1
      ide, H(2)O(2) and CO(2). However, the reaction cross section of [Trp-H](-) is
      strongly suppressed by E(col) and becoming negligible at E(col) > 1.0 eV,
      indicating that this reaction proceeds without energy barriers above the
      reactants.

PMID- 22582859
TI  - Machine learning methods for property prediction in chemoinformatics: Quo Vadis?
AB  - This paper is focused on modern approaches to machine learning, most of which are
      as yet used infrequently or not at all in chemoinformatics. Machine learning
      methods are characterized in terms of the "modes of statistical inference" and
      "modeling levels" nomenclature and by considering different facets of the
      modeling with respect to input/ouput matching, data types, models duality, and
      models inference. Particular attention is paid to new approaches and concepts
      that may provide efficient solutions of common problems in chemoinformatics:
      improvement of predictive performance of structure-property (activity) models,
      generation of structures possessing desirable properties, model applicability
      domain, modeling of properties with functional endpoints (e.g., phase diagrams
      and dose-response curves), and accounting for multiple molecular species (e.g.,
      conformers or tautomers).

PMID- 22582860
TI  - Genomic profiling to assess the clonal relationship between histologically
      distinct intracranial tumours.

PMID- 22582861
TI  - California almond shelf life: lipid deterioration during storage.
AB  - The effects of storage conditions on the lipid deterioration in California almond
      nuts and sliced were studied. Natural whole almonds with or without polyethylene
      (PE) packaging and blanched whole almonds and sliced with PE packaging were
      stored in 10 different storage conditions which were combinations of different
      temperatures and relative humidity levels. The peroxide values (PVs), iodine
      values (IVs), and free fatty acids (FFAs) were monitored during the storage. The
      PVs in the natural samples did not change noticeably whereas the blanched samples
      changed greatly, indicating that skins may have played a significant role. The
      IVs decreased slightly in the 1st 150 d of storage and then leveled off. The
      slightly faster changes in IVs in the blanched samples coincided with the greater
      changes in PVs in the blanched samples. The natural samples exhibited much higher
      FFA levels than the blanched samples after storage. In general, FFA increased
      with increasing storage time, temperature, and humidity. Highest levels of FFA
      were observed in the samples stored at high temperature and high humidity.
      PRACTICAL APPLICATION: The results reported in this article provide useful
      information that almond producers and processors could use to develop their
      storage and transport processes.

PMID- 22582862
TI  - Probing nucleation pathways for morphological manipulation of platinum
      nanocrystals.
AB  - Understanding the formation process in the controlled synthesis of nanocrystals
      will lead to the effective manipulation of the morphologies and properties of
      nanomaterials. Here, in-situ UV-vis and X-ray absorption spectroscopies are
      combined to monitor the tracks of the nucleation pathways in the solution
      synthesis of platinum nanocrystals. We find experimentally that the control over
      nucleation pathways through changing the strength of reductants can be
      efficiently used to manipulate the resultant nanocrystal shapes. The in-situ
      measurements show that two different nucleation events involving the formation of
      one-dimensional "Pt(n)Cl(x)" complexes from the polymerization of linear "Cl(3)Pt
      PtCl(3)" dimers and spherical "Pt(n)(0)" clusters from the aggregation of Pt(0)
      atoms occur for the cases of weak and strong reductants; and the resultant
      morphologies are nanowires and nanospheres, respectively. This study provides a
      crucial insight into the correlation between the particle shapes and nucleation
      pathways of nanomaterials.

PMID- 22582864
TI  - Three new compounds from the marine-derived fungus Trichoderma atroviride G20-12.
AB  - Three new compounds, 4'-(4,5-dimethyl-1,3-dioxolan-2-yl)methyl-phenol (1), (3'
      hydroxybutan-2'-yl)5-oxopyrrolidine-2-carboxylate (2), and atroviridetide (3),
      have been isolated from the marine-derived fungus Trichoderma atroviride G 20-12.
      Their structures were determined on the basis of chemical and spectroscopic
      methods.

PMID- 22582863
TI  - Equivalency of buffalo (Bubalus bubalis) embryonic stem cells derived from
      fertilized, parthenogenetic, and hand-made cloned embryos.
AB  - This study was aimed at establishing buffalo embryonic stem cells (ESCs) from in
      vitro fertilized (IVF), parthenogenetic, and hand-made cloned (HMC) embryos and
      to check their equivalency in terms of stem cell marker expression, longevity,
      proliferation, and differentiation pattern. ESCs derived from all three sources
      were found by immunofluorescence to express the pluripotency markers SSEA-4, TRA
      1-60, TRA-1-81, OCT4, and SOX2 and were able to form embryoid bodies containing
      cells expressing genes specific to endoderm (AFP, HNF4, and GATA4), mesoderm
      (MSX1, BMP4, and ASA), and ectoderm (cytokeratin 8 and NF68). Reverse
      transcriptase PCR (RT-PCR) showed cells from all sources to be positive for
      pluripotency markers OCT4, SOX2, NANOG, STAT3, REX1, FOXD3, NUCLEOSTEMIN, and
      TELOMERASE. Pluripotency markers OCT4, SOX2, NANOG, and c-MYC were also analyzed
      by real-time PCR. No significant differences were observed among ESCs from all
      three sources for all these genes except NANOG, whose expression was higher
      (p<0.05) in HMC-derived ESCs (6.897+/-2.3) compared to that in parthenogenesis-
      and IVF-derived cells (1.603+/-0.315 and 1+/-0, respectively). Pluripotent,
      stable buffalo ESC lines derived from IVF, parthenogenesis, and HMC embryos may
      be genetically manipulated to provide a powerful tool for studies involving
      embryonic development, genomic imprinting, gene targeting, cloning, chimera
      formation, and transgenic animal production.

PMID- 22582865
TI  - Reactions of brominated naphthalene diimide with bis(tributylstannyl)acetylene: a
      simple approach for conjugated polymers and versatile coupling intermediates.
AB  - A new synthetic approach to 1,4,5,8-naphthalenetetracarboxylic diimide (NDI)
      containing materials and conjugates is described. A simple one-step Stille
      coupling procedure is used to create either novel alkyne-linked NDI polymers or a
      new stannylated diyne synthetic building block that provides a flexible approach
      to new NDI conjugates and polymers.

PMID- 22582866
TI  - A mixed model approach to meta-analysis of diagnostic studies with binary test
      outcome.
AB  - We propose 2 related models for the meta-analysis of diagnostic tests. Both
      models are based on the bivariate normal distribution for transformed
      sensitivities and false-positive rates. Instead of using the logit as a
      transformation for these proportions, we employ the talpha family of
      transformations that contains the log, logit, and (approximately) the
      complementary log. A likelihood ratio test for the cutoff value problem is
      developed, and summary receiver operating characteristic (SROC) curves are
      discussed. Worked examples showcase the methodology. We compare the models to the
      hierarchical SROC model, which in contrast employs a logit transformation. Data
      from various meta-analyses are reanalyzed, and the reanalysis indicates a better
      performance of the models based on the talpha transformation.

PMID- 22582868
TI  - Ag@AgI, core@shell structure in agarose matrix as hybrid: synthesis,
      characterization, and antimicrobial activity.
AB  - A novel in situ core@shell structure consisting of nanoparticles of Ag (Ag Nps)
      and AgI in agarose matrix (Ag@AgI/agarose) has been synthesized as a hybrid, in
      order to have an efficient antibacterial agent for repetitive usage with no
      toxicity. The synthesized core@shell structure is very well characterized by XRD,
      UV-visible, photoluminescence, and TEM. A detailed antibacterial studies
      including repetitive cycles are carried out on Gram-negative Escherichia coli (E.
      coli) and Gram-positive Staphylococcus aureus (S. aureus) bacteria in saline
      water, both in dark and on exposure to visible light. The hybrid could be
      recycled for the antibacterial activity and is nontoxic toward human cervical
      cancer cells (HeLa cells). The water insoluble Ag@AgI in agarose matrix forms a
      good coating on quartz, having good mechanical strength. EPR and TEM studies are
      carried out on the Ag@AgI/agarose and the bacteria, respectively, to elucidate a
      possible mechanism for killing of the bacteria.

PMID- 22582869
TI  - Expression and localization of TLR4 and its negative regulator Tollip in the
      placenta of early-onset and late-onset preeclampsia.
AB  - OBJECTIVE: Toll-like receptor 4 (TLR4) is a key component of the innate arm of
      the immune system that mediates inflammatory responses following exposure to
      bacterial lipopolysaccharides. In doing so, TLR4 may contribute to the
      pathogenesis of preeclampsia (PE). We sought to assess the spatio-temporal
      expression of TLR4 and its negative regulator Toll-interacting protein (Tollip)
      in placental tissues from normal and preeclamptic pregnancies. METHODS: Using
      immunohistochemistry and immunoblotting, we investigated the localization of TLR4
      and its negative regulator Tollip in first- and third-trimester human placenta.
      RESULTS: TLR4 was found to be expressed in the cytoplasm of trophoblasts in both
      first- (n = 6) and third-trimester (n = 24) placental villous samples. Tollip was
      mainly located in the cytoplasm of cytotrophoblasts in the first-trimester
      placental tissues; in contrast, our analyses of third-trimester placental tissues
      demonstrated that Tollip was mainly located in the decidual cells. Using western
      blot analysis, TLR4 expression was shown to be significantly higher in early
      onset PE tissues than control group placentas (n = 8 for each group, p < 0.01).
      However, we were unable to detect a significant difference between late-onset PE
      and normal controls (n = 8 for each group, p = 0.119). CONCLUSION: These data
      demonstrate the novel observation that TLR4 may play a much more important role
      in early-onset PE. Interestingly, the spatial expression of Tollip at different
      stages of gestation may play an important role in the pathophysiology of PE.

PMID- 22582870
TI  - A mass spectrometric multicenter study supports classification of preeclampsia as
      heterogeneous disorder.
AB  - OBJECTIVE: The diagnostic value of affinity-based matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry analysis to distinguish
      preeclampsia (PE) from matched controls was tested in a multicenter setting.
      METHODS: Serum samples of preeclamptic (n = 60) and healthy pregnant women (n =
      66) from four centers were prospectively analyzed with predefined rule sets.
      RESULTS: Overall sample classification reached sensitivity of 0.88 and
      specificity of 0.73. Separate calculations for early-onset PEs only (before 34
      weeks of gestation) revealed sensitivity of 0.88 and specificity of 0.89.
      CONCLUSION: Matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry serum-profiling with center-wise standardization offers a fast and
      robust method to classify PE and contributes to the theory of PE being a
      heterogeneous disorder that ought to be subclassified.

PMID- 22582871
TI  - When "conservative" anionic tracers aren't.

PMID- 22582872
TI  - The effects of loperamide, or loperamide plus simethicone, on the distribution of
      gut water as assessed by MRI in a mannitol model of secretory diarrhoea.
AB  - BACKGROUND: Loperamide (LOP) is an anti-diarrhoeal agent which is thought to act
      largely by slowing transit with an uncertain effect on the fluid content of the
      small and large bowel in humans. Adding simethicone (SIM) to LOP improves its
      efficacy, but the mechanism of interaction is unclear. Novel MRI techniques to
      assess small bowel water content (SBWC) have shown that mannitol solutions
      markedly increase SBWC and can be used as a model of diarrhoea. AIM: We aimed to
      use quantitative MRI techniques to compare the actions in the gut of LOP and LOP
      + SIM in a model of secretory diarrhoea using mannitol. METHODS: A total of 18
      healthy volunteers ingested capsules containing placebo (PLA) or 12 mg LOP or 12
      mg LOP + 125 mg SIM. After 100 min they were given a drink containing 5% mannitol
      in 350 mL of water. They underwent baseline fasting and postprandial serial MRI
      scans at 45 min intervals for 4.5 h after ingesting the drink. A range of MRI
      sequences was acquired to image the gut. RESULTS: LOP and LOP + SIM significantly
      accelerated gastric emptying (P < 0.03) and reduced SBWC during the late phase
      (135-270 min after mannitol ingestion), P < 0.009, while delaying arrival of
      fluid in the ascending colon (AC). The relaxation time T2 of the contents of the
      AC was reduced by both drugs (P < 0.0001). CONCLUSIONS: LOP and LOP + SIM
      accelerate gastric emptying, but reduce small bowel water content which may
      contribute to the delay in oral-caecal transit and overall anti-diarrhoeal
      effect.

PMID- 22582873
TI  - Human salivary cystatin SA exhibits antimicrobial effect against Aggregatibacter
      actinomycetemcomitans.
AB  - BACKGROUND AND OBJECTIVE: Healthy subjects who do not have Aggregatibacter
      actinomycetemcomitans in their oral cavity may possess factors in saliva that
      might demonstrate antibacterial activity against the bacterium. The aim of this
      study was to identify and purify proteins from saliva of healthy subjects that
      might demonstrate antibacterial activity against A. actinomycetemcomitans and
      test the same against the bacteria. MATERIAL AND METHODS: Saliva from 10 healthy
      volunteers was tested individually for its anti-A. actinomycetemcomitans
      activity. Among the 10 subjects, eight demonstrated anti-A. actinomycetemcomitans
      activity. Saliva was collected from one healthy volunteer who demonstrated the
      highest antimicrobial activity against A. actinomycetemcomitans. After clarifying
      the saliva, it was subjected to an affinity chromatography column with A.
      actinomycetemcomitans. The proteins bound to A. actinomycetemcomitans were eluted
      from the column and identified using mass spectrometry (MALDI-TOF/TOF MS). Among
      other proteins that bound to A. actinomycetemcomitans, which included
      lactoferrin, immunoglobulin A and kallikrein, cystatin SA was observed in
      significantly higher concentrations, and this was purified from the eluate. The
      purified cystatin SA was tested at different concentrations for its ability to
      kill A. actinomycetemcomitans in a 2 h cell killing assay. The bacteria were also
      treated with a proteinase inhibitor, leupeptin, to clarify whether the
      antimicrobial effect of cystatin SA was related to its protease inhibitory
      function. Cystatin SA was also tested for its ability to prevent binding of A.
      actinomycetemcomitans to buccal epithelial cells (BECs) in an A.
      actinomycetemcomitans-BEC binding assay. RESULTS: Cystatin SA (0.1 mg/mL)
      demonstrated a statistically significant antimicrobial activity against A.
      actinomycetemcomitans. The effect of cystatin SA decreased with lower
      concentrations, with 0.01 mg/mL showing no effect. The addition of monoclonal
      cystatin SA antibodies to the purified sample completely negated the
      antimicrobial effect. Treatment of A. actinomycetemcomitans with leupeptin
      resulted in no antimicrobial effect, suggesting that the antimicrobial activity
      of cystatin SA is independent of its protease inhibitory function. A.
      actinomycetemcomitans pretreated with cystatin SA showed reduced binding to BECs,
      suggesting a potential role for cystatin SA in decreasing the colonization of A.
      actinomycetemcomitans. CONCLUSION: The present study shows that cystatin SA
      demonstrates antimicrobial activity against the periodontopathogen A.
      actinomycetemcomitans, and future studies determining the mechanism of action are
      necessary. The study also shows the ability of cystatin SA to reduce
      significantly the binding of A. actinomycetemcomitans to BECs.

PMID- 22582867
TI  - Behavioural vs. molecular sources of conflict between nuclear and mitochondrial
      DNA: the role of male-biased dispersal in a Holarctic sea duck.
AB  - Genetic studies of waterfowl (Anatidae) have observed the full spectrum of
      mitochondrial (mt) DNA population divergence, from apparent panmixia to deep,
      reciprocally monophyletic lineages. Yet, these studies often found weak or no
      nuclear (nu) DNA structure, which was often attributed to male-biased gene flow,
      a common behaviour within this family. An alternative explanation for this
      'conflict' is that the smaller effective population size and faster sorting rate
      of mtDNA relative to nuDNA lead to different signals of population structure. We
      tested these alternatives by sequencing 12 nuDNA introns for a Holarctic pair of
      waterfowl subspecies, the European goosander (Mergus merganser merganser) and the
      North American common merganser (M. m. americanus), which exhibit strong
      population structure in mtDNA. We inferred effective population sizes, gene flow
      and divergence times from published mtDNA sequences and simulated expected
      differentiation for nuDNA based on those histories. Between Europe and North
      America, nuDNA F(ST)  was 3.4-fold lower than mtDNA F(ST) , a result consistent
      with differences in sorting rates. However, despite geographically structured and
      monophyletic mtDNA lineages within continents, nuDNA F(ST)  values were generally
      zero and significantly lower than predicted. This between- and within-continent
      contrast held when comparing mtDNA and nuDNA among published studies of ducks.
      Thus, male-mediated gene flow is a better explanation than slower sorting rates
      for limited nuDNA differentiation within continents, which is also supported by
      nonmolecular data. This study illustrates the value of quantitatively testing
      discrepancies between mtDNA and nuDNA to reject the null hypothesis that conflict
      simply reflects different sorting rates.

PMID- 22582874
TI  - Recognition of cello-oligosaccharides by CBM17 from Clostridium cellulovorans :
      molecular dynamics simulation.
AB  - The basic function of carbohydrate binding module (CBM) is believed to enhance
      local concentration of glycosidases on the carbohydrate molecule, and thus
      facilitates the subsequent degradation of carbohydrate. Full understanding of the
      recognition mechanism of carbohydrates by CBM can be helpful to enhance the
      enzyme activity. In this work, the detailed recognition specificity of two
      soluble cello-oligosaccharide substrates, cellotetraose and cellohexaose, by a
      family 17 CBM from  Clostridium cellulovorans  was investigated by molecular
      dynamics simulation. Calculated binding free energies using molecular
      mechanics/generalized Born and surface area (MM/GBSA) approach are in excellent
      agreement with experimental values. Overall, based on the decomposition of total
      binding free energy, nonpolar terms are shown to have favorable contributions to
      the binding, while polar interactions make unfavorable contributions, no matter
      significant hydrogen bond network is formed between substrate and protein. On the
      basis of computational alanine scanning and per-residue free energy
      decomposition, Trp88 and Trp135 are shown to be two most important residues in
      the cellohexaose binding mainly via hydrophobic interactions. The calculated
      subtotal contributions for those polar residues, D54, R92, Q129, and N185, can
      compare very well with experimental data.

PMID- 22582875
TI  - Long-term balanced fertilization decreases arbuscular mycorrhizal fungal
      diversity in an arable soil in North China revealed by 454 pyrosequencing.
AB  - A balanced fertilization can increase crop yields partly due to stimulated
      microbial activities and growths. In this study, we investigated arbuscular
      mycorrhizal fungi (AMF) in arable soils to determine the optimal practices for an
      effective fertilization. We used pyrosequencing-based approach to study AMF
      diversity, as well as their responses to different long-term (>20 years)
      fertilizations, including OM (organic manure) and mix chemical fertilizers of NP
      (nitrogen-phosphorus), NK (nitrogen-potassium), and NPK (nitrogen-phosphorus
      potassium). Results revealed that 124,998 of 18S rRNA gene fragments were
      dominated by Glomeromycota with 59,611 sequences, generating 70 operational
      taxonomic units (OTUs), of which the three largest families were Glomeraceae,
      Gigasporaceae and Acaulosporaceae. In Control and NK plots, AMF diversity and
      richness significantly decreased under long-term P fertilizations, such as NP,
      NPK, and OM. Concomitantly, the AMF community structure shifted. Supported by
      canonical correspondence analysis, we hereby propose that long-term balanced
      fertilization, especially P fertilizer with additional N fertilizer, helps the
      build-up of soil nutrients. Consequently, some AMF community constituents are
      sacrificed, propelled by the self-regulation of plant-AMF-microbes system,
      resulting in an agro-ecosystem with a better sustainability. This knowledge would
      be valuable toward better understandings of AMF community in agro-ecosystem, and
      long-term ecosystem benefits of the balanced fertilization.

PMID- 22582876
TI  - Optimizing the orosensory properties of model functional beverages: the influence
      of novel sweeteners, odorants, bitter blockers, and their mixtures on (+)
      catechin.
AB  - The use of flavor-modifying strategies are important to improving the sensory
      profile of some excessively bitter and astringent functional ingredients, such as
      (+)-catechin (CAT). Two bitter blockers (beta-cyclodextrin [CYCLO],
      homoeriodictyol sodium salt [HED]), two sweeteners (sucrose [SUC], rebaudioside A
      [REB]), and two odorants (vanillin [VAN], black tea aroma [TEA]) were assessed
      for their efficacy at modifying the bitterness and astringency of CAT in model
      aqueous solutions. The intensity of oral sensations elicited by CAT was
      determined in duplicate in binary, ternary, and quaternary mixtures of these
      stimuli by a trained panel (n = 15) using a 15 cm visual analogue scale. Overall,
      bitterness and astringency were most effectively reduced by ternary solutions
      containing CYCLO + REB or CYCLO + SUC (68%, 60%, and 45%, 43% for bitterness and
      astringency, respectively). Odorants were not effective at modifying the
      bitterness or astringency of CAT. We conclude that the use of select bitter
      blockers and sweeteners may be of value in optimizing the flavor and acceptance
      of functional food and beverages fortified with phenolic compounds. PRACTICAL
      APPLICATION: (+)-Catechin is a bitter-tasting plant-derived health-promoting
      phenolic compound of interest to functional food and beverage manufacturers. We
      investigated the efficacy of bitter blockers, plant-based sweeteners, and
      odorants in decreasing the bitterness and astringency elicited by (+)-catechin.
      Some of these additives, both alone and in combination, reduced bitterness and
      astringency, and may therefore assist in optimizing the flavor and consumer
      acceptance of some phenolic-based functional foods and beverages.

PMID- 22582877
TI  - Absence of anionic phospholipids in  Kluyveromyces lactis  cells is fatal without
      F1-catalysed ATP hydrolysis.
AB  - We have shown in previous research that the loss of phosphatidylglycerol and
      cardiolipin caused by disruption of the PGS1 gene is lethal for the petite
      negative yeast  Kluyveromyces lactis . This present study demonstrates the role
      and mechanism of atp2.1 in the suppression of pgs1 lethality in K. lactis cells.
      Phenotypic characterization has shown that a strain lacking the
      phosphatidylglycerolphosphate synthase (atp2.1pgs1Delta) possessed a markedly
      impaired respiratory chain, very low endogenous respiration, and uncoupled
      mitochondria. As a result the mutant strain was unable to generate a sufficient
      mitochondrial membrane potential via respiration. The atp2.1 suppressor mutation
      enabled an increase in the affinity of F(1)-ATPase for ATP in the hydrolytic
      reaction, resulting in the maintenance of sufficient membrane potential for the
      biogenesis of mitochondria and survival of cells lacking anionic phospholipid
      biosynthesis.

PMID- 22582879
TI  - High-intensity 405 nm light inactivation of Listeria monocytogenes.
AB  - The antimicrobial properties of light is an area of increasing interest. This
      study investigates the sensitivity of the significant foodborne pathogen Listeria
      monocytogenes to selected wavelengths of visible light. Results demonstrate that
      exposure to wavelength region 400-450 nm, at sufficiently high dose levels (750 J
      cm(-2)), induced complete inactivation of a 5 log(10) population. Exposure to
      wavelengths longer than 450 nm did not cause significant inactivation. Analysis
      of 10 nm bandwidths between 400 and 450 nm confirmed 405(+/- 5) nm light to be
      most effective for the inactivation of L. monocytogenes, with a lesser
      bactericidal effect also evident at other wavelengths between 400 and 440 nm.
      Identification of the optimum bactericidal wavelength enabled the comparison of
      inactivation using 405(+/- 5) nm filtered light and a 405 nm light-emitting diode
      (LED) array (14 nm FWHM). Results demonstrate similar inactivation kinetics,
      indicating that the applied dose of 405 nm light is the important factor. Use of
      the 405 nm LED array for the inactivation of L. monocytogenes and other Listeria
      species resulted in similar kinetics, with up to 5 log(10) reductions with a dose
      of 185 J cm(-2). Comparative data for the 405 nm light inactivation of L.
      monocytogenes and other important foodborne pathogens, Escherichia coli,
      Salmonella enteritidis and Shigella sonnei, are also presented, with L.
      monocytogenes showing higher susceptibility to inactivation through 405 nm light
      exposure.

PMID- 22582878
TI  - Chromosome demise in the wake of ligase-deficient replication.
AB  - Bacterial DNA ligases, NAD+-dependent enzymes, are distinct from eukaryotic ATP
      dependent ligases, representing promising targets for broad-spectrum
      antimicrobials. Yet, the chromosomal consequences of ligase-deficient DNA
      replication, during which Okazaki fragments accumulate, are still unclear. Using
      ligA251(Ts), the strongest ligase mutant of Escherichia coli, we studied ligase
      deficient DNA replication by genetic and physical approaches. Here we show that
      replication without ligase kills after a short resistance period. We found that
      double-strand break repair via RecA, RecBCD, RuvABC and RecG explains the
      transient resistance, whereas irreparable chromosomal fragmentation explains
      subsequent cell death. Remarkably, death is mostly prevented by elimination of
      linear DNA degradation activity of ExoV, suggesting that non-allelic double
      strand breaks behind replication forks precipitate DNA degradation that enlarge
      them into allelic double-strand gaps. Marker frequency profiling of synchronized
      replication reveals stalling of ligase-deficient forks with subsequent
      degradation of the DNA synthesized without ligase. The mechanism that converts
      unsealed nicks behind replication forks first into repairable double-strand
      breaks and then into irreparable double-strand gaps may be behind lethality of
      any DNA damaging treatment.

PMID- 22582880
TI  - The importance of attractive three-point interaction in enantioselective surface
      chemistry: stereospecific adsorption of serine on the intrinsically chiral
      Cu{531} surface.
AB  - Both enantiomers of serine adsorb on the intrinsically chiral Cu{531} surface in
      two different adsorption geometries, depending on the coverage. At saturation,
      substrate bonds are formed through the two oxygen atoms of the carboxylate group
      and the amino group (MU3 coordination), whereas at lower coverage, an additional
      bond is formed through the deprotonated beta-OH group (MU4 coordination). The
      latter adsorption geometry involves substrate bonds through three side groups of
      the chiral center, respectively, which leads to significantly larger enantiomeric
      differences in adsorption geometries and energies compared to the MU3
      coordination, which involves only two side groups. This relatively simple model
      system demonstrates, in direct comparison, that attractive interactions of three
      side groups with the substrate are much more effective in inducing strong
      enantiomeric differences in heterogeneous chiral catalyst systems than hydrogen
      bonds or repulsive interactions.

PMID- 22582881
TI  - Accumulation of a repulsive axonal guidance molecule RGMa in amyloid plaques: a
      possible hallmark of regenerative failure in Alzheimer's disease brains.
AB  - AIMS: RGMa is a repulsive guidance molecule that induces the collapse of axonal
      growth cones by interacting with the receptor neogenin in the central nervous
      system during development. It remains unknown whether RGMa plays a role in the
      neurodegenerative process of Alzheimer's disease (AD). We hypothesize that RGMa,
      if it is concentrated on amyloid plaques, might contribute to a regenerative
      failure of degenerating axons in AD brains. METHODS: By immunohistochemistry, we
      studied RGMa and neogenin (NEO1) expression in the frontal cortex and the
      hippocampus of 6 AD and 12 control cases. The levels of RGMa expression were
      determined by qRT-PCR and Western blot in cultured human astrocytes following
      exposure to cytokines and amyloid beta (Abeta) peptides. RESULTS: In AD brains,
      an intense RGMa immunoreactivity was identified on amyloid plaques and in the
      glial scar. In the control brains, the glial scar and vascular foot processes of
      astrocytes expressed RGMa immunoreactivity, while oligodendrocytes and microglia
      were negative for RGMa. In AD brains, a small subset of amyloid plaques expressed
      a weak NEO1 immunoreactivity, while some reactive astrocytes in both AD and
      control brains showed an intense NEO1 immunoreactivity. In human astrocytes,
      transforming growth factor beta-1 (TGFbeta1 ), Abeta 1-40 or Abeta 1-42 markedly
      elevated the levels of RGMa, and TGFbeta1 also increased its own levels.
      Coimmunoprecipitation analysis validated the molecular interaction between RGMa
      and the C-terminal fragment beta of amyloid beta precursor protein (APP).
      Furthermore, recombinant RGMa protein interacted with amyloid plaques in situ.
      CONCLUSIONS: RGMa, produced by TGFbeta-activated astrocytes and accumulated in
      amyloid plaques and the glial scar, could contribute to the regenerative failure
      of degenerating axons in AD brains.

PMID- 22582882
TI  - Characterization, optimisation and process robustness of a co-processed mannitol
      for the development of orally disintegrating tablets.
AB  - This is a study to fully assess a commercially available co-processed mannitol
      for its usefulness as an off-the-shelf excipient for developing orally
      disintegrating tablets (ODTs) by direct compression on a pilot scale (up to 4
      kg). This work encompassed material characterization, formulation optimisation
      and process robustness. Overall, this co-processed mannitol possessed favourable
      physical attributes including low hygroscopicity and compactibility. Two design
      of-experiments (DoEs) were used to screen and optimise the placebo formulation.
      Xylitol and crospovidone concentrations were found to have the most significant
      impact on disintegration time (p < 0.05). Higher xylitol concentrations retarded
      disintegration. Avicel PH102 promoted faster disintegration than PH101, at higher
      levels of xylitol. Without xylitol, higher crospovidone concentrations yielded
      faster disintegration and reduced tablet friability. Lubrication sensitivity
      studies were later conducted at two fill loads, three levels for lubricant
      concentration and number of blend rotations. Even at 75% fill load, the design
      space plot showed that 1.5% lubricant and 300 blend revolutions were sufficient
      to manufacture ODTs with <= 0.1% friability and disintegrated within 15 s. This
      study also describes results using a modified disintegration method based on the
      texture analyzer as an alternative to the USP method.

PMID- 22582884
TI  - Stimulus onsets and distraction in younger and older adults.
AB  - Changes in task performance that accompany healthy aging are often attributed to
      age-impaired inhibitory control. For example, Maylor and Lavie (1998)
      demonstrated greater interference in older than younger people for response
      incompatible visual distractors presented peripherally to a central low-load
      task. Here we explore the possible contribution of age-related changes in bottom
      up visual processing in this task, and specifically the effect of the abrupt
      visual onsets associated with the distractors. In Experiment 1, with distractors
      presented as abrupt onsets, we replicated Maylor and Lavie's (1998) effect. In
      Experiment 2, when placeholders preceded the stimuli to eliminate the abrupt
      onsets, response-incompatible distractors had a markedly reduced effect relative
      to neutral distractors, for older participants in particular. Stimuli presented
      as abrupt visual onsets, therefore, capture attention differentially depending
      upon the stimulus identity in combination with the age of the individual, with
      the greatest effects here for response-incompatible distractors in older people.
      We conclude that age-related differences in basic bottom-up processes may
      contribute to many purported declines in higher-level functioning in older
      people. More generally, this study provides further evidence for the interaction,
      and nonadditivity, of stimulus-driven and goal-driven influences in determining
      processing priorities across the age span.

PMID- 22582883
TI  - Partially overlapping mechanisms of language and task control in young and older
      bilinguals.
AB  - The current study tested the hypothesis that bilinguals rely on domain-general
      mechanisms of executive control to achieve language control by asking if
      linguistic and nonlinguistic switching tasks exhibit similar patterns of aging
      related decline. Thirty young and 30 aging bilinguals completed a cued language
      switching task and a cued color-shape switching task. Both tasks demonstrated
      significant aging effects, but aging-related slowing and the aging-related
      increase in errors were significantly larger on the color-shape than on the
      language task. In the language task, aging increased language-switching costs in
      both response times and errors, and language-mixing costs only in response times.
      In contrast, the color-shape task exhibited an aging-related increase in costs
      only in mixing errors. Additionally, a subset of the older bilinguals could not
      do the color-shape task, but were able to do the language task, and exhibited
      significantly larger language-switching costs than matched controls. These
      differences, and some subtle similarities, in aging effects observed across tasks
      imply that mechanisms of nonlinguistic task and language control are only partly
      shared and demonstrate relatively preserved language control in aging. More
      broadly, these data suggest that age deficits in switching and mixing costs may
      depend on task expertise, with mixing deficits emerging for less-practiced tasks
      and switching deficits for highly practiced, possibly "expert" tasks (i.e.,
      language).

PMID- 22582886
TI  - Three new acyclic diterpenoids from Eupatorium lindleyanum DC.
AB  - Three new acyclic diterpenoids were isolated from the whole plant of Eupatorium
      lindleyanum DC. The structures of the compounds were elucidated by means of (1)H
      and (13)C NMR spectroscopic analyses, including 2D NMR experiments.

PMID- 22582885
TI  - Personality, self-rated health, and subjective age in a life-span sample: the
      moderating role of chronological age.
AB  - The present study tested whether chronological age moderates the association
      between subjective age and self-rated health and personality in a community
      dwelling life-span sample (N = 1,016; age range: 18-91 years). Self-rated health,
      extraversion, and openness to experience were associated with a younger
      subjective age at older ages. Conscientious individuals felt more mature early in
      life. Conscientiousness, neuroticism, and agreeableness were not related to
      subjective age at older ages. These findings suggest that with aging self-rated
      health and personality traits are increasingly important for subjective age.

PMID- 22582888
TI  - Zinc(II) mediated imine-enamine tautomerization.
AB  - Reduction of imine-anthracenone compounds selectively produces secondary alcohols
      leaving the external imine group unreacted. Addition of the Zn(II) ion induces a
      metal-mediated imine-enamine tautomerization reaction that is selective for
      Zn(II), a new fluorescence detection method not previously observed for this
      important cation.

PMID- 22582887
TI  - A description of the lumbar interfascial triangle and its relation with the
      lateral raphe: anatomical constituents of load transfer through the lateral
      margin of the thoracolumbar fascia.
AB  - Movement and stability of the lumbosacral region is contingent on the balance of
      forces distributed through the myofascial planes associated with the
      thoracolumbar fascia (TLF). This structure is located at the common intersection
      of several extremity muscles (e.g. latissimus dorsi and gluteus maximus), as well
      as hypaxial (e.g. ventral trunk muscles) and epaxial (paraspinal) muscles. The
      mechanical properties of the fascial constituents establish the parameters
      guiding the dynamic interaction of muscle groups that stabilize the lumbosacral
      spine. Understanding the construction of this complex myofascial junction is
      fundamental to biomechanical analysis and implementation of effective
      rehabilitation in individuals with low back and pelvic girdle pain. Therefore,
      the main objectives of this study were to describe the anatomy of the lateral
      margin of the TLF, and specifically the interface between the fascial sheath
      surrounding the paraspinal muscles and the aponeurosis of the transversus
      abdominis (TA) and internal oblique (IO) muscles. The lateral margin of the TLF
      was exposed via serial reduction dissections from anterior and posterior
      approaches. Axial sections (cadaveric and magnetic resonance imaging) were
      examined to characterize the region between the TA and IO aponeurosis and the
      paraspinal muscles. It is confirmed that the paraspinal muscles are enveloped by
      a continuous paraspinal retinacular sheath (PRS), formed by the deep lamina of
      the posterior layer of the TLF. The PRS extends from the spinous process to
      transverse process, and is distinct from both the superficial lamina of the
      posterior layer and middle layer of the TLF. As the aponeurosis approaches the
      lateral border of the PRS, it appears to separate into two distinct laminae,
      which join the anterior and posterior walls of the PRS. This configuration
      creates a previously undescribed fat-filled lumbar interfascial triangle situated
      along the lateral border of the paraspinal muscles from the 12th rib to the iliac
      crest. This triangle results in the unification of different fascial sheaths
      along the lateral border of the TLF, creating a ridged-union of dense connective
      tissue that has been termed the lateral raphe (Spine, 9,1984, 163). This triangle
      may function in the distribution of laterally mediated tension to balance
      different viscoelastic moduli, along either the middle or posterior layers of the
      TLF.

PMID- 22582890
TI  - Height and survival at older ages among men born in an inland village in Sardinia
      (Italy), 1866-2006.
AB  - This study investigated the relationship between individual height and survival
      at older ages among conscripts born between 1866 and 1915 in an inland village of
      Sardinia, Italy. Individual age at death was related to military height
      measurement at age 20. Differential longevity of conscripts at older ages was
      investigated through the comparison of age-specific mortality rates and life
      expectancy estimates. Results indicated that short conscripts (<161.1 cm)
      generally had higher survival rates than their tall peers (>= 161.1 cm). At 70
      years of age, tall peers were expected to live two years less than short
      conscripts. Biological mechanisms were examined in relation to the greater
      longevity of shorter people.

PMID- 22582889
TI  - Role of active mentoring during flexible ureteroscopy training.
AB  - PURPOSE: To evaluate the outcome of flexible ureteroscopy training with or
      without an active mentor. MATERIALS AND METHODS: Thirty-six flexible ureteroscopy
      naive practicing urologists and urology residents, after an initial introductory
      refreshment course, underwent training under a mentor for 15 minutes each in a
      high-fidelity nonvirtual reality Endo-Urologie-Modell (Karl Storz). The trainees
      were then randomized into two equal groups for training: One under a mentor and
      the other without. These two groups completed the training for 2 hours. Global
      rating scale (GRS) for the performance of flexible ureteroscopy was measured by a
      blinded expert at the beginning and end of the training. A specific task
      completion time (TCT) was noted at the end of the training. The trainees noted
      their own global rating scale at the end of the training. RESULTS: The GRS by the
      expert at the end of the training was significantly higher in the mentor group.
      TCT was significantly lower in the mentor group. TCT correlated well with the GRS
      as measured by the expert rather than the trainee. CONCLUSION: Mentorship during
      flexible ureteroscopy training results in higher GRS and lower TCT at the end of
      the training. Self-assessment GRS by trainee does not correlate well with the
      skills acquired.

PMID- 22582892
TI  - Education and health among U.S. working-age adults: a detailed portrait across
      the full educational attainment spectrum.
AB  - This article presents detailed estimates of relative and absolute health
      inequalities among U.S. working-age adults by educational attainment, including
      six postsecondary schooling levels. We also estimate the impact of several sets
      of mediating variables on the education-health gradient. Data from the 1997-2009
      National Health Interview Survey (N = 178,103) show remarkable health
      differentials. For example, high school graduates have 3.5 times the odds of
      reporting "worse" health than do adults with professional or doctoral degrees.
      The probability of fair or poor health in mid-adulthood is less than 5 percent
      for adults with the highest levels of education but over 20 percent for adults
      without a high school diploma. The probability of reporting excellent health in
      the mid-forties is below 25 percent among high school graduates but over 50
      percent for those adults who have professional degrees. These health differences
      characterize all the demographic subgroups examined in this study. Our results
      show that economic indicators and health behaviors explain about 40 percent of
      the education-health relationship. In the United States, adults with the highest
      educational degrees enjoy a wide array of benefits, including much more favorable
      self-rated health, compared to their less-educated counterparts.

PMID- 22582893
TI  - Social and demographic dimensions of sex selection technologies: review and
      analysis of the research literature.
AB  - Using the Thomson Reuters Web of Science, we analytically reviewed existing
      research from the past 30 years on the social and demographic dimensions of sex
      selection technologies. Through content analysis and bibliometric analysis, we
      investigated publications in four categories: description, attitudes,
      demographics, and policy. Our results leave little doubt that individual choices
      and, in some instances, public policies have the potential to bring about
      significant social and demographic changes on local, national, and international
      levels. More research is warranted on the causal variables that underlie the
      individual and policy decisions that are associated with sex selection
      technologies.   [Supplementary material is available for this article. Go to the
      publisher's online edition of Biodemography and Social Biology for the following
      free supplemental resource(s): Sex Selection References for all references
      reviewed in both the content analysis and the bibliometric analysis not otherwise
      listed in the References section].

PMID- 22582891
TI  - Biodemography of exceptional longevity: early-life and mid-life predictors of
      human longevity.
AB  - This study explores the effects of early-life and middle-life conditions on
      exceptional longevity using two matched case-control studies. The first study
      compares 198 validated centenarians born in the United States between 1890 and
      1893 to their shorter-lived siblings. Family histories of centenarians were
      reconstructed and exceptional longevity validated using early U.S. censuses, the
      Social Security Administration Death Master File, state death indexes, online
      genealogies, and other supplementary data resources. Siblings born to young
      mothers (aged less than 25 years) had significantly higher chances of living to
      100 compared to siblings born to older mothers (odds ratio = 2.03, 95% CI = 1.33
      3.11, p = .001). Paternal age and birth order were not associated with
      exceptional longevity. The second study explores whether people living to 100
      years and beyond differ in physical characteristics at a young age from their
      shorter-lived peers. A random representative sample of 240 men who were born in
      1887 and survived to age 100 was selected from the U.S. Social Security
      Administration database and linked to U.S. World War I civil draft registration
      cards collected in 1917 when these men were 30 years old. These validated
      centenarians were then compared to randomly selected controls who were matched by
      calendar year of birth, race, and place of draft registration in 1917. Results
      showed a negative association between "stout" body build (being in the heaviest
      15 percent of the population) and survival to age 100. Having the occupation of
      "farmer" and a large number of children (4 or more) at age 30 increased the
      chances of exceptional longevity. The results of both studies demonstrate that
      matched case-control design is a useful approach in exploring effects of early
      life conditions and middle-life characteristics on exceptional longevity.

PMID- 22582894
TI  - Topical application of lipopolysaccharide into gingival sulcus promotes
      periodontal destruction in rats immunized with lipopolysaccharide.
AB  - BACKGROUND AND OBJECTIVE: The causes of periodontitis are bacteria and the host
      immune system, but the role of the immune system in the onset and progression of
      periodontal disease is still unclear. Our previous report showed that the
      formation of an immune complex in the gingival sulcus induces periodontal
      destruction. This study was carried out to investigate how the immune system,
      particularly immunization, is involved in periodontal destruction. MATERIAL AND
      METHODS: Animals immunized intraperitoneally with lipopolysaccharide (LPS) were
      used as the immunized group. The nonimmunized group received only phosphate
      buffered saline. LPS was applied daily onto the palatal gingival sulcus in both
      groups 1 d after the booster injection. Serum levels of anti-LPS IgG were
      determined. Loss of attachment and the level of alveolar bone were
      histopathologically and histometrically investigated. RANKL-bearing cells and the
      expression of C1qB were immunohistologically evaluated. RESULTS: The serum levels
      of anti-LPS IgG were elevated in the early experimental period in the immunized
      group. There were significant increases in loss of attachment, level of alveolar
      bone and the number of RANKL-bearing cells in the immunized group. C1qB was
      observed in the junctional epithelium and adjacent connective tissue. The
      nonimmunized group showed similar findings at and after the time when the serum
      level of anti-LPS IgG was elevated. CONCLUSION: Topical application of LPS as an
      antigen induced periodontal destruction when the serum level of anti-LPS IgG was
      elevated in rats immunized with LPS. The presence of C1qB suggests that the
      formation of immune complexes is involved in this destruction.

PMID- 22582895
TI  - Oxidative stress status and DNA damage in saliva of human subjects with oral
      lichen planus and oral squamous cell carcinoma.
AB  - BACKGROUND: The aim of this study was to evaluate oxidative stress status in the
      saliva of patients with oral lichen planus (OLP) and oral squamous cell carcinoma
      (OSCC). METHODS: Thirty-two patients with OLP, 26 patients with OSCC, and 30 non
      involved subjects were enrolled in this study. The study was conducted at the
      Cancer Department, Clinic of Oral Medicine, Tehran University of Medical
      Sciences. The unstimulated whole saliva malondialdehyde (MDA), as an indicator of
      lipid peroxidation, the total antioxidant capacity (TAC), and 8-hydroxy-2'
      deoxyguanosine (8-OHdG) were assayed by thiobarbituric acid, ferric reducing
      antioxidant potential (FRAP), and ELISA method, respectively. The TAC/MDA ratio
      was used as an index of oxidative stress status. Data were analyzed by ANOVA
      followed by the Tukey's post hoc test. RESULTS AND CONCLUSION: There were no
      significant differences in saliva TAC and MDA levels between OLP and control, and
      also between OLP and OSCC patients. MDA and 8-OHdG were significantly higher but
      TAC was lower in OSCC patients than control. TAC/MDA ratio was significantly
      lower in patients with OSCC than both OLP patients and control. TAC/MDA ratio was
      significantly lower but 8-OHdG was higher in patients with OLP compared to
      control. This suggests that patients with OLP and OSCC are more susceptible to an
      imbalance of antioxidant-oxidative stress status.

PMID- 22582896
TI  - Novel function of scutellarin in inhibiting cell proliferation and inducing cell
      apoptosis of human Burkitt lymphoma Namalwa cells.
AB  - Anti-lymphoma therapy continues to present a major challenge. Even though
      cytotoxic therapy, immunotherapy and molecularly targeted therapy have been used
      in the clinic to treat the disease, effective anti-lymphoma drugs are still
      needed. In this study, we explored novel anti-lymphoma agents and found that
      scutellarin, an active component of a traditional Chinese medicinal herb Erigeron
      breviscapus, executed an anti-lymphoma effect. Scutellarin diminished the
      proliferation of B-lymphoma Namalwa cells in vitro and inhibited lymphoma growth
      in Namalwa cell-xenotransplanted mice without obvious toxicity. A mechanism study
      showed that scutellarin at doses of less than 10 MUM induced cell cycle arrest at
      G0/G1 transition without the induction of cell apoptosis, which was accompanied
      by down-regulation of cyclin D1 and CDK4 expression. In contrast, scutellarin at
      concentrations of 15 MUM or above promoted Namalwa cell apoptosis, which was
      partially associated with the activation of caspases. These results suggest that
      scutellarin is a new potential anti-lymphoma candidate.

PMID- 22582897
TI  - Molecular characterization of hot spring cyanobacteria and evaluation of their
      photoprotective compounds.
AB  - Phylogenetic analysis of 4 cyanobacterial strains isolated from hot springs in
      Rajgir, India, was carried out using the 16S rRNA gene (1400 bp). These strains
      were identified as members of Chroococcales ( Cyanothece  sp. strain HKAR-1) and
      Nostocales ( Nostoc  sp. strain HKAR-2,  Scytonema  sp. strain HKAR-3, and 
      Rivularia  sp. strain HKAR-4). Furthermore, we evaluated the presence of
      ultraviolet-screening and (or) photoprotective compounds, such as mycosporine
      like amino acids (MAAs) and scytonemin, in these cyanobacteria by using high
      performance liquid chromatography. Well-characterized MAAs, including the
      critical and highly polar compounds shinorine, porphyra-334, and mycosporine
      glycine, as well as several unknown MAAs, were found in these hot-spring
      inhabiting microorganisms. The presence of scytonemin was detected only in
      Scytonema sp. strain HKAR-3 and Rivularia sp. strain HKAR-4. The results indicate
      that hot spring cyanobacteria, namely Cyanothece, Nostoc, Scytonema, and
      Rivularia, belonging to different groups possess various photoprotective
      compounds to cope up with the negative impacts of damaging radiations.

PMID- 22582898
TI  - Heat shock treatments: a new safe approach against lichen growth on outdoor stone
      surfaces.
AB  - The control of lichen growth, particularly important in the field of stone
      conservation of outdoor monuments, largely depends on the use of biocides, that
      may be dangerous for the users, the environment and the substratum. A new,
      alternative approach is proposed, which makes the most of a poorly known
      peculiarity of poikilohydrous organisms: they are thermo-tolerant (up to 65-70 
      degrees C) when dry, but thermo-sensitive when wet. The efficacy of thermal
      treatments (range: 20-55  degrees C), in parallel to the application of three
      biocides, was verified in the laboratory with six epi- and endolithic lichens.
      Chlorophyll a fluorescence emission was checked in treated and nontreated samples
      of all the species, whereas histochemical observations with a dead cell stain
      were carried out on one of them. The feasibility of the thermal treatments in the
      field was verified with a seventh species. The results confirm that a 6 h
      treatment at 55  degrees C is sufficient to kill the lichens if they are kept
      fully hydrated. At 40  degrees C the organisms are damaged: in this case biocides
      at concentrations 10* lower than in normal applications can profitably be used.
      The new protocol is simple, the field equipment cheap, and the negative effects
      associated with standard biocide treatments are absent.

PMID- 22582899
TI  - Do extraverts get more bang for the buck? Refining the affective-reactivity
      hypothesis of extraversion.
AB  - One of the most robust observations in personality and emotion research is the
      finding that extraverts are happier than introverts. Some theorists have
      attributed this to differential reactivity of the brain reward system, which is
      central to many biologically inspired models of extraversion. This affective
      reactivity hypothesis, which suggests that extraverts should be more susceptible
      to the induction of positive affect, has so far received very mixed empirical
      support. In this article, we consider a more biologically plausible account of
      extraverts' affective-reactivity. Over 5 experiments, we demonstrate that
      extraverts show greater affective-reactivity only in response to clearly
      appetitive stimuli and situations (e.g., where rewards are being pursued).
      Conversely, after merely pleasant stimuli and situations (without any reward
      approach element), extraverts and introverts respond similarly. We also show that
      it is specifically activated affect (e.g., feelings of alertness), rather than
      pleasantly valenced affect (e.g., feelings of contentment), that characterizes
      the affective-reactivity of extraverts. Such reactions may potentially facilitate
      the reward-seeking behavior associated with extraversion, but they seem unlikely
      to explain the broadly happy disposition of extraverts.

PMID- 22582900
TI  - Ovulation leads women to perceive sexy cads as good dads.
AB  - Why do some women pursue relationships with men who are attractive, dominant, and
      charming but who do not want to be in relationships--the prototypical sexy cad?
      Previous research shows that women have an increased desire for such men when
      they are ovulating, but it is unclear why ovulating women would think it is wise
      to pursue men who may be unfaithful and could desert them. Using both college-age
      and community-based samples, in 3 studies we show that ovulating women perceive
      charismatic and physically attractive men, but not reliable and nice men, as more
      committed partners and more devoted future fathers. Ovulating women perceive that
      sexy cads would be good fathers to their own children but not to the children of
      other women. This ovulatory-induced perceptual shift is driven by women who
      experienced early onset of puberty. Taken together, the current research
      identifies a novel proximate reason why ovulating women pursue relationships with
      sexy cads, complementing existing research that identifies the ultimate,
      evolutionary reasons for this behavior.

PMID- 22582901
TI  - So near and yet so far: the mental representation of goal progress.
AB  - In the present article, we explore whether people's mental representation of
      progress level can function as a self-regulation mechanism that helps motivate
      continued effort in the pursuit. We propose that when individuals have just
      started pursuing a goal and have accumulated only limited progress, they
      exaggerate the achieved progress level in their mental representation to signal a
      higher chance of eventual goal attainment and thus elicit greater effort. In
      contrast, when people have made substantial progress and are approaching the goal
      attainment, they downplay the achieved progress in their mental representation to
      create greater perceived discrepancy, hence eliciting greater effort. Empirical
      evidence from 4 studies supported the hypothesis.

PMID- 22582902
TI  - An endohedral single-molecule magnet with long relaxation times: DySc2N@C80.
AB  - The magnetism of DySc(2)N@C(80) endofullerene was studied with X-ray magnetic
      circular dichroism (XMCD) and a magnetometer with a superconducting quantum
      interference device (SQUID) down to temperatures of 2 K and in fields up to 7 T.
      XMCD shows hysteresis of the 4f spin and orbital moment in Dy(III) ions. SQUID
      magnetometry indicates hysteresis below 6 K, while thermal and nonthermal
      relaxation is observed. Dilution of DySc(2)N@C(80) samples with C(60) increases
      the zero-field 4f electron relaxation time at 2 K to several hours.

PMID- 22582903
TI  - Retinal photodamage by endogenous and xenobiotic agents.
AB  - The human eye is constantly exposed to sunlight and artificial lighting. Light
      transmission through the eye is fundamental to its unique biological functions of
      directing vision and circadian rhythm and therefore light absorbed by the eye
      must be benign. However, exposure to the very intense ambient radiation can pose
      a hazard particularly if the recipient is over 40 years of age. There are age
      related changes in the endogenous (natural) chromophores (lipofuscin, A2E and all
      trans-retinal derivatives) in the human retina that makes it more susceptible to
      visible light damage. Intense visible light sources that do not filter short blue
      visible light (400-440 nm) used for phototherapy of circadian imbalance (i.e.
      seasonal affective disorder) increase the risk for age-related light damage to
      the retina. Moreover, many drugs, dietary supplements, nanoparticles and
      diagnostic dyes (xenobiotics) absorb ocular light and have the potential to
      induce photodamage to the retina, leading to transient or permanent blinding
      disorders. This article will review the underlying reasons why visible light in
      general and short blue visible light in particular dramatically raises the risk
      of photodamage to the human retina.

PMID- 22582904
TI  - Optimization of propranolol HCl release kinetics from press coated sustained
      release tablets.
AB  - Press-coated sustained release tablets offer a valuable, cheap and easy
      manufacture alternative to the highly expensive, multi-step manufacture and
      filling of coated beads. In this study, propranolol HCl press-coated tablets were
      prepared using hydroxylpropylmethylcellulose (HPMC) as tablet coating material
      together with carbopol 971P and compressol as release modifiers. The prepared
      formulations were optimized for zero-order release using artificial neural
      network program (INForm, Intelligensys Ltd, North Yorkshire, UK). Typical zero
      order release kinetics with extended release profile for more than 12 h was
      obtained. The most important variables considered by the program in optimizing
      formulations were type and proportion of polymer mixture in the coat layer and
      distribution ratio of drug between core and coat. The key elements found were;
      incorporation of 31-38 % of the drug in the coat, fixing the amount of polymer in
      coat to be not less than 50 % of coat layer. Optimum zero-order release kinetics
      (linear regression r2 = 0.997 and Peppas model n value > 0.80) were obtained when
      2.5-10 % carbopol and 25-42.5% compressol were incorporated into the 50 % HPMC
      coat layer. 

PMID- 22582906
TI  - Home care or long-term care? Setting the balance of care in urban and rural
      Northwestern Ontario, Canada.
AB  - The objective of the study was to determine the extent to which community care
      packages could be provided at a lower cost than facility-based long-term care
      (LTC) for 864 individuals on the LTC waiting list in urban and rural parts of
      Northwestern Ontario, Canada. A sequential mixed methods design was used
      entailing a retrospective chart review, the formation of case vignettes, the
      creation of community care packages with an 'expert panel' of care managers, the
      costing of care packages and the calculation of potential diversion rates from
      LTC. Data collection took place in Northwestern Ontario between the months of
      March and June 2008. Eight per cent of individuals in the urban area and 50% of
      individuals from the rural areas could potentially be safely diverted to the
      community and provided with a community care package at a cost lower than
      facility-based LTC. There is potential for home and community care to substitute
      for more costly long-term care, but doing so requires building capacity in this
      sector, particularly in rural areas, which are currently underserviced.
      Reconfiguring the 'balance of care' may lead to long-term cost efficiencies for
      an ageing population.

PMID- 22582905
TI  - Impaired mouse mammary gland growth and development is mediated by melatonin and
      its MT1G protein-coupled receptor via repression of ERalpha, Akt1, and Stat5.
AB  - To determine whether melatonin, via its MT(1)  G protein-coupled receptor,
      impacts mouse mammary gland development, we generated a mouse mammary tumor virus
      (MMTV)-MT1-Flag-mammary gland over-expressing (MT1-mOE) transgenic mouse.
      Increased expression of the MT(1) -Flag transgene was observed in the mammary
      glands of pubescent MT1-mOE transgenic female mice, with further significant
      increases during pregnancy and lactation. Mammary gland whole mounts from MT1-mOE
      mice showed significant reductions in ductal growth, ductal branching, and
      terminal end bud formation. Elevated MT(1)  receptor expression in pregnant and
      lactating female MT1-mOE mice was associated with reduced lobulo-alveolar
      development, inhibition of mammary epithelial cell proliferation, and significant
      reductions in body weights of suckling pups. Elevated MT(1)  expression in
      pregnant and lactating MT1-mOE mice correlated with reduced mammary gland
      expression of Akt1, phospho-Stat5, Wnt4, estrogen receptor alpha, progesterone
      receptors A and B, and milk proteins beta-casein and whey acidic protein.
      Estrogen- and progesterone-stimulated mammary gland development was repressed by
      elevated MT(1)  receptor expression and exogenous melatonin administration. These
      studies demonstrate that the MT(1)  melatonin receptor and its ligand melatonin
      play an important regulatory role in mammary gland development and lactation in
      mice through both growth suppression and alteration of developmental paradigms.

PMID- 22582907
TI  - A new auronol from Cudrania cochinchinensis.
AB  - A new auronol, cudrauronol (1), was isolated from the roots of Cudrania
      cochinchinensis along with 10 known compounds, 1,3,5-trihydroxy-4-prenylxanthone
      (2), 1,3,7-trihydroxy-4-prenylxanthone (3), 3,4',5,7-tetrahydroxydihydroflavonol
      (4), kaempferol (5), 3,6-dihydroxy-1,5-dimethoxyxanthone (6), 2',4',5,7
      tetrahydroxyflavanolol (7), 3,7-dihydroxy-1-methoxyxanthone (8), 1,3,5
      trihydroxyxanthone (9), cudraflavone B (10), and 2'-oxyresveratrol (11).
      Compounds 1-8 were evaluated for anti-inflammatory activity on lipopolysaccharide
      induced nitric oxide production in RAW 264.7 macrophages. Compounds 2-5 were more
      active than aminoguanidine, with IC(50) values of 8.8, 23.2, 27.1, and 11.9 MUM,
      respectively.

PMID- 22582908
TI  - Hydroxychloroquine and smoking in patients with cutaneous lupus erythematosus.
AB  - Antimalarials, such as chloroquine and hydroxychloroquine, have been used to
      treat cutaneous and systemic lupus erythematosus for decades with excellent
      therapeutic efficacy. Smoking seems to inhibit the therapeutic efficacy of
      antimalarials when treating cutaneous lupus erythematosus (CLE), but the reason
      behind this observation is unclear. In addition, antimalarials have been
      associated with several potentially serious adverse effects, including
      irreversible loss of vision. The aim of this literature review is to discuss the
      evidence for how cigarette smoking interferes with antimalarial efficacy in the
      treatment of CLE. Evidence-based data with long-term follow-up will allow
      determination of the aetiology for diminished antimalarial response, and enable
      selection of the best treatment to maximize long-term remission in CLE.

PMID- 22582909
TI  - Acute generalized exanthematous pustulosis induced by the essential oil of
      Pistacia lentiscus.
AB  - Acute generalized exanthematous pustulosis (AGEP) is an uncommon pustular
      eruption characterized by small nonfollicular pustules on an erythematous
      background, sometimes associated with fever and neutrophilia. Over 90% of cases
      are drug-induced; however, it can be caused in rare cases by other agents. We
      report two cases of AGEP secondary to ingestion of Pistacia lentiscus essential
      oil, the first two such cases to our knowledge. The cutaneous morphology, disease
      course and histological findings were consistent with a definite diagnosis of
      AGEP, based on the criteria of the EuroSCAR study group. These two cases
      highlight the need to consider herbal extracts as a potential rare cause of AGEP
      and to ensure the safety of herbal medicines.

PMID- 22582910
TI  - Narrowband ultraviolet B phototherapy associated with improvement in Netherton
      syndrome.
AB  - Netherton syndrome (NS) is a rare and severe autosomal recessive ichthyosis. We
      report the case of a patient with NS treated successfully with narrowband
      ultraviolet B (NB-UVB) phototherapy after failure of low-dose oral isotretinoin.
      A 16-year-old girl born to consanguineous parents presented with severe
      ichthyosis. On examination of her hair, she was found to have trichorrhexis
      invaginata. Genetic analysis revealed a SPINK5 mutation specific for NS. The
      patient's cousin had the same mutation. The patient developed Cushing syndrome
      after long-term application of topical steroids. She was treated with low-dose
      oral isotretinoin with no benefit. NB-UVB phototherapy was started, which
      resulted in marked improvement after 2 months. In conclusion, we report a case of
      NS with failure of low-dose oral isotretinoin, for which NB-UVB phototherapy,
      through its apoptosis-inducing and immunomodulatory effects, was effective.
      However, long-term use of UVB is limited by its potential side-effects.

PMID- 22582911
TI  - Methyl aminolevulinate plus red light vs. placebo plus red light in the treatment
      of photodamaged facial skin: histopathological findings.
AB  - BACKGROUND: Improvement in the morphological appearance of collagen and elastic
      fibres has been reported after the use of trichloroacetic acid, dermabrasion and
      laser therapy, but the histopathological changes occurring after photodynamic
      therapy are less understood. AIM: To assess the histological changes that occur
      after methyl aminolevulinate (MAL) plus red-light therapy for facial photodamage.
      METHODS: This was a prospective, double-blind, double-arm, randomized, placebo
      controlled trial of MAL plus red light in patients with facial photodamage. A 3
      mm punch biopsy was taken from each side of the face before randomization and
      start of therapy. A dermatopathologist blinded to the treatment assessed
      epidermal and dermal layer thickness, perivascular inflammation, solar elastosis,
      perifollicular fibrosis, telangiectasias, number of elastic and collagen fibres,
      and grade of reticular degeneration. RESULTS: In total, 65 women were initially
      screened for eligibility, but skin samples from only 38 of these were analysed.
      The change in dermal thickness from baseline to postintervention was significant
      (P < 0.01, Wilcoxon signed rank test). Although there was a trend for the
      epidermis to be thinner after MAL plus red light vs. placebo plus red light
      (46.25 MUm vs. 55.50 MUm, respectively), the difference was not significant (P =
      0.64, Mann-Whitney U-test). Similarly, the changes in dermal thickness obtained
      with the two treatments were not significant (P = 0.99, Mann-Whitney test).
      Histological improvement was seen using stains for collagen, elastic tissue, and
      perifollicular fibrosis after MAL plus red light therapy. DISCUSSION: Dermal
      thickness increased after the use of MAL plus red light, and there was
      improvement in collagen, elastic tissue and perifollicular fibrosis. Although
      these differences were not significant, most of the histopathological features
      examined in our study improved after treatment with MAL plus red light. The lack
      of significance might be due either to the low power of this study or to the
      failure of our scoring method to detect significant histopathological
      differences.

PMID- 22582912
TI  - Characterization of the phenotype of high collagen-producing fibroblast clones in
      systemic sclerosis, using a new modified limiting-dilution method.
AB  - BACKGROUND: Overproduction of type I collagen in fibroblasts of systemic
      sclerosis (SSc) is the hallmark of fibrosis. Establishment and characterization
      of the phenotype of SSc fibroblasts has been hindered by the heterogeneity
      between fibroblasts and the lack of adequate cloning methods. AIM: To establish
      and investigate the characteristics of the SSc high collagen-producing fibroblast
      phenotype. METHODS: Primary cultured fibroblasts from skin biopsies of patients
      with SSc and normal controls were cloned by a new modified limiting-dilution
      method. All clones were divided into different subpopulations based on their
      alpha1(I) procollagen (COL1A1) mRNA level detected by real-time reverse
      transcriptase PCR assay. In the different subpopulations, cell growth and cycle
      distribution were analysed by MTT and flow cytometry, COL1A1 promoter activity
      was examined by transient transfection, and the binding activity of Sp1 to the
      COL1A1 proximal promoter was investigated by quantitative chromatin
      immunoprecipitation. RESULTS: The clonogenicities of SSc and normal control
      fibroblasts were similar, but the mean COL1A1 mRNA level of clones and the
      percentage of the subpopulation with a high COL1A1 mRNA level were significantly
      higher in SSc fibroblasts than in controls. There was no significant difference
      on cell growth and cycle between different subpopulations of SSc and control
      fibroblasts. The COL1A1 proximal promoter activity and its binding activity to
      Sp1 in the clones were strongly correlated with their COL1A1 mRNA level.
      CONCLUSION: Overproduction of collagen in an SSc fibroblast subpopulation seems
      to result mainly from the abnormally activated transcription of COL1A1 rather
      than from overproliferation of fibroblasts. The new modified limiting-dilution
      method provides a useful means for characterizing cells with heterogeneous
      phenotypes.

PMID- 22582913
TI  - Bullous pemphigoid associated with the use of topical diclofenac.

PMID- 22582914
TI  - Resolution of pancreatic panniculitis following metastasectomy.

PMID- 22582915
TI  - The use of etanercept in the treatment of peristomal pyoderma gangrenosum.

PMID- 22582916
TI  - Joint destruction and presence of small papules on the palms and soles.

PMID- 22582917
TI  - Papular rash with arthritis.

PMID- 22582918
TI  - Erythrodermic pustular psoriasis triggered by intravesical bacillus Calmette
      Guerin immunotherapy.

PMID- 22582919
TI  - Sudden whitening of the hair in an 82-year-old woman: the 'overnight greying'
      phenomenon.

PMID- 22582920
TI  - Evaluation of the nutraceutical, physiochemical and sensory properties of raisin
      jam.
AB  - This objective of this study was to evaluate the effect of jam processing of
      grape and raisin on the nutraceutical, physiochemical, and sensory properties.
      The results showed that fresh grape had the highest antioxidant activity, and
      total phenolic and anthocyanin content followed by grape jam, raisin, and raisin
      jam, respectively. No significant differences existed in soluble solids, pH, or
      firmness between grape and raisin jams. No significant differences in color
      parameters, DeltaE, and chroma existed between grape and raisin jam. Descriptive
      sensory results showed minor differences in some sensory attributes between grape
      and raisin jams. In terms of consumer evaluation (9-point verbal hedonic scale
      and a 5-point just-about-right scale) the jams made from local raisins were
      parity with those from grape, despite small differences especially in whole
      raisin jam. Although raisin and other dried products are not traditionally
      considered as a raw material for jam processing, they have the same potential as
      fresh fruits.

PMID- 22582921
TI  - Ruthenium(II)-catalyzed synthesis of hydroxylated arenes with ester as an
      effective directing group.
AB  - An unprecedented Ru(II) catalyzed ortho-hydroxylation has been developed for the
      facile synthesis of a variety of multifunctionalized arenes from easily
      accessible ethyl benzoates with ester as an efficient directing group. Both the
      TFA/TFAA cosolvent system and oxidants serve as the critical success factors in
      this transformation. The reaction demonstrates excellent reactivity, good
      functional group tolerance, and high yields.

PMID- 22582922
TI  - Gastrointestinal stromal tumors: evolving role of the multidisciplinary team
      approach in management.
AB  - Gastrointestinal stromal tumors (GISTs) are rare tumors of the GI tract arising
      from mesenchymal cells. Treatment options include surgical resection and medical
      therapy with imatinib. A summary of National Comprehensive Cancer Network and
      European Society of Medical Oncology clinical practice guidelines relating to
      GIST management are presented here. A multidisciplinary team of physicians is
      essential to the successful treatment of GIST. Evidence supports
      multidisciplinary team management with a gastroenterologist, surgeon, medical
      oncologist, pathologist and radiologist. Consultations between them are
      recommended to ensure optimal care of patients with GIST. The role for individual
      core team workers is highlighted. The benefits of multidisciplinary disease
      management of patients include reducing recurrent disease, optimizing timing of
      surgery and organ preservation, prolonging survival for the patient and enhancing
      response to targeted therapies.

PMID- 22582923
TI  - Role of high endothelial postcapillary venules and selected adhesion molecules in
      periodontal diseases: a review.
AB  - Periodontitis is accompanied by the proliferation of small blood vessels in the
      gingival lamina propria. Specialized postcapillary venules, termed periodontal
      high endothelial-like venules, are also present, and demonstrate morphological
      and functional traits similar to those of high endothelial venules (HEVs) in
      lymphatic organs. The suggested role of HEVs in the pathogenesis of chronic
      periodontitis involves participation in leukocyte transendothelial migration and
      therefore proinflammatory effects appear. Recent observations suggest that
      chronic periodontitis is an independent risk factor for systemic vascular disease
      and may result in stimulation of the synthesis of acute phase protein by
      cytokines released by periodontal high endothelial cells (HECs). However, tissue
      expression of HEV-linked adhesion molecules has not been evaluated in the gingiva
      of patients with chronic periodontitis. This is significant in relation to
      potential therapy targeting expression of the adhesion molecules. In this review,
      current knowledge of HEV structure and the related expression of four surface
      adhesion molecules of HECs [CD34, platelet endothelial cell adhesion molecule 1,
      endoglin and intercellular adhesion molecule 1 (ICAM-1)], involved in the key
      steps of the adhesion cascade in periodontal diseases, are discussed. Most
      studies on the expression of adhesion molecules in the development and
      progression of periodontal diseases pertain to ICAM-1 (CD54). Studies by the
      authors demonstrated quantitatively similar expression of three of four selected
      surface markers in gingival HEVs of patients with chronic periodontitis and in
      HEVs of reactive lymph nodes, confirming morphological and functional similarity
      of HEVs in pathologically altered tissues with those in lymphoid tissues.

PMID- 22582924
TI  - Maternal heart rate analysis during labor. Has the time come for computerized
      analysis?

PMID- 22582926
TI  - The NtrY/X two-component system of Brucella spp. acts as a redox sensor and
      regulates the expression of nitrogen respiration enzymes.
AB  - Brucella spp. are facultative intracellular bacteria pathogenic for many
      mammalian species including humans, causing a disease called brucellosis.
      Learning how Brucella adapts to its intracellular niche is crucial for
      understanding its pathogenesis mechanism, allowing for the development of new and
      more effective vaccines and treatments against brucellosis. Brucella pathogenesis
      resides mostly in its ability to adapt to the harsh environmental conditions
      encountered during host infection such as the oxygen depletion. The mechanism by
      which Brucella senses the oxygen tension and triggers its environmental
      adaptation is unknown. In this work we show that the Brucella abortus NtrY/NtrX
      two-component system is involved in oxygen sensing through a haem group contained
      in a Per-ARNT-SIM (PAS) domain of the NtrY histidine kinase. The NtrY haem iron
      can be reduced to the ferrous form and is rapidly oxidized to the ferric form in
      presence of oxygen. Importantly, we show that the oxidation state of the haem
      iron modulates the autokinase activity, being the anoxygenic reduced ferrous form
      the signalling state of NtrY. Also, we show that ntrY gene expression increases
      under low oxygen tension and that NtrY transfers its signal to its cognate
      response regulator NtrX, regulating in this way the expression of nitrogen
      respiration enzymes. Based on these findings, we postulate that NtrY acts as a
      redox sensor in Brucella spp.

PMID- 22582927
TI  - Transformations of nanomaterials in the environment.
AB  - Increasing use of engineered nanomaterials with novel properties relative to
      their bulk counterparts has generated a need to define their behaviors and
      impacts in the environment.  The high surface area to volume ratio of
      nanoparticles results in highly reactive and physiochemically dynamic materials
      in environmental media. Many transformations, e.g. reactions with
      biomacromolecules, redox reactions, aggregation, and dissolution, may occur in
      both environmental and biological systems. These transformations and others will
      alter the fate, transport, and toxicity of nanomaterials.  The nature and extent
      of these transformations must be understood before significant progress can be
      made toward understanding the environmental risks posed by these materials.

PMID- 22582928
TI  - The impact of substituents on the transition states of SN2 and E2 reactions in
      aliphatic and vinylic systems: remarkably facile vinylic eliminations.
AB  - For a series of alpha and beta substituted haloethanes and haloethenes, gas-phase
      experiments and computational modeling have been used to characterize their
      nucleophilic substitution and elimination reactions. Despite being less
      thermodynamically favorable, the vinylic eliminations have rate constants and
      computed barriers that are similar to those of analogous aliphatic eliminations.
      This is the result of the vinylic systems shifting to more E1(cb)-like transition
      states and exploiting the inherent greater acidity of vinylic hydrogens. In
      general, the alpha-substituents have a greater impact on the S(N)2 pathways and
      stabilize the transition states via field and polarizability effects. Substantial
      stabilization is also provided to the E2 transition states by the alpha
      substituents, but they have surprisingly little impact on the geometries of the
      transition states of either pathway. The beta-substituents generally lead to a
      strong bias toward elimination and greatly affect the synchronicity of the
      elimination (more E1(cb)-like) as well as its location on the reaction coordinate
      (early). The experimental and computational data are in good accord, and the full
      data set provides a comprehensive picture of substituent effects on solvent-free
      S(N)2 and E2 processes.

PMID- 22582930
TI  - Tomato fruit continues growing while ripening, affecting cuticle properties and
      cracking.
AB  - Fruit cuticle composition and their mechanical performance have a special role
      during ripening because internal pressure is no longer sustained by the degraded
      cell walls of the pericarp but is directly transmitted to epidermis and cuticle
      which could eventually crack. We have studied fruit growth, cuticle modifications
      and its biomechanics, and fruit cracking in tomato; tomato has been considered a
      model system for studying fleshy fruit growth and ripening. Tomato fruit cracking
      is a major disorder that causes severe economic losses and, in cherry tomato,
      crack appearance is limited to the ripening process. As environmental conditions
      play a crucial role in fruit growing, ripening and cracking, we grow two cherry
      tomato cultivars in four conditions of radiation and relative humidity (RH). High
      RH and low radiation decreased the amount of cuticle and cuticle components
      accumulated. No effect of RH in cuticle biomechanics was detected. However,
      cracked fruits had a significantly less deformable (lower maximum strain) cuticle
      than non-cracked fruits. A significant and continuous fruit growth from mature
      green to overripe has been detected with special displacement sensors. This
      growth rate varied among genotypes, with cracking-sensitive genotypes showing
      higher growth rates than cracking-resistant ones. Environmental conditions
      modified this growth rate during ripening, with higher growing rates under high
      RH and radiation. These conditions corresponded to those that favored fruit
      cracking. Fruit growth rate during ripening, probably sustained by an internal
      turgor pressure, is a key parameter in fruit cracking, because fruits that
      ripened detached from the vine did not crack.

PMID- 22582931
TI  - Meso-tetrakis(p-sulfonatophenyl)N-confused porphyrin tetrasodium salt: a
      potential sensitizer for photodynamic therapy.
AB  - A water-soluble derivative of N-confused porphyrin (NCP) was synthesized, and the
      photodynamic therapeutic (PDT) application was investigated by photophysical and
      in vitro studies. High singlet oxygen quantum yield in water at longer wavelength
      and promising IC(50) values in a panel of cancer cell lines ensure the potential
      candidacy of the sensitizer as a PDT drug. Reactive oxygen species (ROS)
      generation on PDT in MDA-MB 231 cells and the apoptotic pathway of cell death was
      illustrated using different techniques.

PMID- 22582932
TI  - The education science train has left the station: how do I get on board?

PMID- 22582933
TI  - Significant differences in pediatric psychotropic side effects: Implications for
      school performance.
AB  - Some side effects (SEs) of increasingly prescribed psychotropic medications can
      impact student performance in school. SE risk varies, even among drugs from the
      same class (e.g., antidepressants). Knowing which SEs occur significantly more
      often than others may enable school psychologists to enhance collaborative risk
      benefit analysis, medication monitoring, data-based decision-making, and inform
      mitigation efforts. SE data from Full Prescribing Information (PI) on the FDA
      website for ADHD drugs, atypical antipsychotics, and antidepressants with
      pediatric indications were analyzed. Risk ratios (RR) are reported for each drug
      within a category compared with placebo. RR tables and graphs inform the reader
      about SE incidence differences for each drug and provide clear evidence of the
      wide variability in SE incidence in the FDA data. Breslow-Day and Cochran Mantel
      Haenszel methods were used to test for drug-placebo SE differences and to test
      for significance across drugs within each category based on odds ratios (ORs).
      Significant drug-placebo differences were found for each drug compared with
      placebo, when odds were pooled across all drugs in a category compared with
      placebo, and between some drugs within categories. Unexpectedly, many large RR
      differences did not reach significance. Potential explanations are offered,
      including limitations of the FDA data sets and statistical and methodological
      issues. Future research directions are offered. The potential impact of certain
      SEs on school performance, mitigation strategies, and the potential role of the
      school psychologist is discussed, with consideration for ethical and legal
      limitations.

PMID- 22582934
TI  - Relations between resiliency, diabetes-related quality of life, and disease
      markers to school-related outcomes in adolescents with diabetes.
AB  - The current study examined the role that resiliency and diabetes quality of life
      play in school functioning and glucose control among adolescents with diabetes.
      Participants included 45 adolescents with diabetes who participated in a larger
      study evaluating the feasibility of a model of mental health screening,
      assessment, and referral/service coordination. We hypothesized that aspects of
      resiliency (e.g., self-mastery, optimism, interpersonal relations, emotional
      control) would be related to self-reported grades and glucose control Hemoglobin
      A1c (HbA1c). We also hypothesized that the relation between resiliency and HbA1c
      would be mediated by blood glucose monitoring. We found that self-mastery (i.e.,
      the perception that one has the ability to overcome challenges and solve
      problems) predicted self-reported school grades. Fewer diabetes-related worries
      and parental reports of less school-related problems (e.g., absences, problems
      with teacher) also predicted better grades. Females and youth with less
      disruptive behaviors and higher levels of self-mastery were less likely to be
      viewed by parents as having problems in school. Self-mastery, in addition to
      later age of onset and more frequent blood glucose monitoring, predicted lower
      HbA1c. The mediational model could not be tested because the same components of
      resiliency that related to blood glucose monitoring did not relate to HbA1c. This
      study suggests that evaluation of positive attributes of adolescents,
      particularly the self-mastery component of resiliency, and consideration to the
      adolescents' perceptions of how diabetes affects their lives, may assist in
      understanding how these adolescents perform in school and manage their diabetes.

PMID- 22582935
TI  - Direct behavior rating scales as screeners: a preliminary investigation of
      diagnostic accuracy in elementary school.
AB  - This study presents an evaluation of the diagnostic accuracy and concurrent
      validity of Direct Behavior Rating Single Item Scales for use in school-based
      behavior screening of second-grade students. Results indicated that each behavior
      target was a moderately to highly accurate predictor of behavioral risk. Optimal
      universal screening cut scores were also identified for each scale, with results
      supporting reduced false positive rates through the simultaneous use of multiple
      scales.

PMID- 22582936
TI  - Teachers' perspectives on providing support to children after trauma: a
      qualitative study.
AB  - A considerable number of children are exposed to extreme stressors such as the
      sudden loss of a loved one, serious traffic accidents, violence, and disaster. In
      order to facilitate school psychologists' assistance of teachers working with
      traumatized children, this study aimed to explore elementary school teachers'
      perspectives. Using a qualitative design, the study explored the perspectives of
      a purposively varied sample of 21 elementary school teachers (ages 22-55 years;
      with 0.5-30 years of teaching experience; 5 men). The teachers participated in
      semistructured interviews, which were transcribed and analyzed in line with the
      method of "summative analysis" by F. Rapport. Even though some teachers expressed
      confidence in working with children after traumatic exposure and many referred to
      a supportive atmosphere within the school, the most prominent themes in the
      participants' narratives reflected uncertainty about, or a struggle with,
      providing optimal support to children. They searched for a clear role definition
      as well as a good balance in answering conflicting needs of the exposed children
      and classmates, wished for better knowledge and skills, and experienced
      difficulties related to the emotional burden of their work. The findings suggest
      a need for further research into this understudied topic. In addition, the
      identified themes can be used by school psychologists to systematically explore
      individual teachers' strengths and difficulties and to provide them with tailored
      advice and training.

PMID- 22582937
TI  - Pioneer marine biofilms on artificial surfaces including antifouling coatings
      immersed in two contrasting French Mediterranean coast sites.
AB  - Marine biofilm communities that developed on artificial substrata were
      investigated using molecular and microscopic approaches. Polystyrene, Teflon(r)
      and four antifouling (AF) paints were immersed for 2 weeks at two contrasting
      sites near Toulon on the French Mediterranean coast (Toulon military harbour and
      the natural protected area of Porquerolles Island). Biofilms comprising bacteria
      and diatoms were detected on all the coatings. The population structure as well
      as the densities of the microorganisms differed in terms of both sites and
      coatings. Lower fouling densities were observed at Porquerolles Island compared
      to Toulon harbour. All bacterial communities (analysed by PCR-DGGE) showed
      related structure, controlled both by the sites and the type of substrata.
      Pioneer microalgal communities were dominated by the same two diatom species,
      viz. Licmophora gracilis and Cylindrotheca closterium, at both sites,
      irrespective of the substrata involved. However, the density of diatoms followed
      the same trend at both sites with a significant effect of all the AF coatings
      compared to Teflon and polystyrene.

PMID- 22582938
TI  - Aberrant microRNA-182 expression is associated with glucocorticoid resistance in
      lymphoblastic malignancies.
AB  - Glucocorticoid (GC) resistance in lymphoblastic malignancies is related to
      treatment failure and is a marker of poor prognosis. Previous studies have
      suggested that microRNA-182 (miR-182) functions as an oncogene and plays a role
      in tumorigenesis, through regulation of FOXO3A. FOXO3A has been implicated in
      tumor suppression and GC-induced apoptosis, suggesting that FOXO3A has potential
      as a therapeutic target. Herein we investigated the role of miR-182 in GC
      sensitivity in lymphoblastic malignancies. Expression of miR-182 was consistently
      higher in human and mouse GC-resistant cell lines than in GC-sensitive cell
      lines. Furthermore, increased expression of miR-182 reduced total FOXO3A
      expression but had no significant effect on phospho-FOXO3A. Additionally Bim, as
      a downstream target of FOXO3A, was reduced by overexpression of miR-182, and
      increased by down-regulation of miR-182. These results demonstrate that miR-182
      is involved in glucocorticoid resistance, via targeting of FOXO3A, and that
      restoration of miR-182 is a potentially promising therapeutic strategy in
      lymphoblastic malignancies.

PMID- 22582940
TI  - Meditations on fifty years as an apolitical plant pathologist.

PMID- 22582939
TI  - PdCl2-catalyzed oxidative cycloisomerization of 3-cyclopropylideneprop-2-en-1
      ones.
AB  - A novel PdCl(2)-catalyzed oxidative cycloisomerization of 3-cyclopropylideneprop
      2-en-1-ones, providing a facile synthesis of highly strained functionalized 2
      alkylidenecyclobutanones via furan-fused cyclobutene intermediates, is reported.
      An interesting route to 2(3H)-furanones with a spiro-cyclopropane unit from the
      obtained 2-alkylidenecyclobutanones via a ring-contraction rearrangement reaction
      is also realized.

PMID- 22582941
TI  - Debate: idiopathic short stature should be treated with growth hormone.
AB  - In this paper we outline the case for and against the treatment of idiopathic
      short stature with growth hormone. Drs Ambler and Fairchild argue that many of
      those with 'idiopathic' short stature are not 'short, normal children' and will
      ultimately receive molecular diagnoses. They also argue that there is a subset of
      children who suffer negative psychosocial consequences of their stature for whom
      growth hormone therapy is effective. Growth hormone has a very good safety record
      and is likely to be as cost-effective in idiopathic short-stature as in some
      other conditions that are currently funded. Dr Wilkinson counters that short
      stature is not associated with physical or psychological illness, and that there
      is no evidence that growth hormone improves psychological or physical wellbeing.
      Moreover, growth hormone for idiopathic short stature represents a form of
      enhancement rather than treatment, and is not a fair use of resources. Socially
      mediated disadvantage should be treated by attention to prejudice and not by
      hormone treatment.

PMID- 22582943
TI  - Antioxidant and antimicrobial properties of various solvent extracts from
      Impatiens balsamina L. stems.
AB  - The antioxidant and antimicrobial activities as well as the quantity of phenolic
      substances of Impatiens balsamina L. stem extracts obtained with various solvent
      were determined in this study. All of the extracts possessed moderate antioxidant
      potential in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and
      reducing power assays. Antimicrobial activity was estimated using the cylinder
      plate and agar dilution methods against four bacterial and six fungal strains.
      The extracts showed good antimicrobial activity especially antifungal activity
      against all of the tested microorganisms. The total phenolic and flavonoid
      contents ranged from 2.88 to 13.63 mg gallic acid equivalents/g dried extract and
      0.98 to 7.87 mg quercetin equivalents/g dried extract, respectively. The results
      presented here indicate that the I. balsamina stem extracts have antioxidant and
      antimicrobial properties and are therefore a potential source of antioxidant and
      antimicrobial agents for the food and pharmaceutical industries. PRACTICAL
      APPLICATION: Our work indicates that the I. balsamina stem may be a good
      candidate as natural antioxidant and antimicrobial agents. It can be applied in
      food industry for preservation.

PMID- 22582942
TI  - Preterm infants who are prone to distress: differential effects of parenting on
      36-month behavioral and cognitive outcomes.
AB  - BACKGROUND: The differential susceptibility (DS) model suggests that
      temperamentally prone-to-distress infants may exhibit adverse outcomes in
      negative environments but optimal outcomes in positive environments. This study
      explored temperament, parenting, and 36-month cognition and behavior in preterm
      infants using the DS model. We hypothesized that temperamentally prone to
      distress preterm infants would exhibit more optimal cognition and fewer behavior
      problems when early parenting was positive; and less optimal cognition and more
      behavior problems when early parenting was less positive. METHODS: Participants
      included 109 preterm infants (gestation <37 weeks) and their mothers. We assessed
      neonatal risk and basal vagal tone in the neonatal intensive care unit; infant
      temperament and parenting interactions at 9 months post-term; and child behavior
      and cognitive skills at 36 months post-term. Hierarchical regression analyses
      tested study hypotheses. RESULTS: Temperamentally prone-to-distress infants
      exhibited more externalizing problems if they experienced more critical parenting
      at 9 months (beta = -.20, p < 0.05) but fewer externalizing problems with more
      positive parenting. Similarly, variations in maternal positive affect (beta =
      .25, p < .01) and intrusive behaviors (beta = .23, p < .05) at 9 months predicted
      36-month cognition at high but not at low levels of infant temperamental
      distress. Higher basal vagal tone predicted fewer externalizing problems (beta = 
      .19, p < .05). CONCLUSIONS: Early parenting behaviors relate to later behavior
      and development in preterm infants who are temperamentally prone to distress, and
      neonatal basal vagal tone predicts subsequent externalizing behaviors. These
      findings suggest that both biological reactivity and quality of caregiving are
      important predictors for later outcomes in preterm infants and may be considered
      as foci for developmental surveillance and interventions.

PMID- 22582944
TI  - Melatonin inhibits cell proliferation and induces caspase activation and
      apoptosis in human malignant lymphoid cell lines.
AB  - Melatonin exerts strong anti-tumour activity via several mechanisms, including
      anti-proliferative and pro-apoptotic effects in addition to its potent
      antioxidant activity. Several studies have investigated the effects of melatonin
      on haematological malignancies. However, the previous studies investigating
      lymphoid malignancies have been largely restricted to a single type of
      malignancy, Burkitt's lymphoma (BL). Thus, we examined the actions of melatonin
      on the growth and apoptosis in a small panel of cell lines representing different
      human lymphoid malignancies including Ramos (Epstein-Barr virus-negative BL), SU
      DHL-4 (diffuse large B cell lymphoma), DoHH2 (follicular B non-Hodgkin lymphoma)
      and JURKAT (acute T cell leukaemia). We showed that melatonin promotes cell cycle
      arrest and apoptosis in all these cells, although there was marked variations in
      responses among different cell lines (sensitivity; Ramos/DoHH2 > SU-DHL-4 >
      JURKAT). Melatonin-induced apoptosis was relatively rapid, with increased caspase
      3 and PARP cleavage detected within 0.5-1 h following melatonin addition.
      Moreover, there was evidence for rapid processing of both caspase 9, as well as a
      breakdown of the mitochondrial inner transmembrane potential. On the contrary,
      caspase activation was detected only in SU-DHL-4 and Ramos cells following
      melatonin treatment suggesting that the extrinsic pathway does not make a
      consistent contribution to melatonin-induced apoptosis in malignant lymphocytes.
      Although all cell lines expressed the high-affinity melatonin receptors, MT1 and
      MT2, melatonin-induced caspase activation appeared to be independent these
      receptors. Our findings confirm that melatonin could be a potential
      chemotherapeutic/preventive agent for malignant lymphocytes. However, it is
      necessary to take into account that different lymphoid malignancies may differ in
      their response to melatonin.

PMID- 22582945
TI  - Computational study on a HS- sensing reaction utilizing a pyrylium derivative.
AB  - In this paper, we present a comprehensive computational study on the hydrogen
      sulfide sensing mechanism in aqueous solution using a pyrylium derivative. The
      possible sensing mechanisms were investigated under the neutral condition and
      acidic condition in the gas phase and in aqueous solution. The pyrylium
      thiopyrylium transformation under the neutral condition is thermodynamically
      unfavorable, while it is greatly facilitated in the acidic condition catalyzed by
      a hydronium cation. In addition, the UV-vis absorption maxima of pyryliums and
      thiopyryliums were investigated at the TDDFT/B3LYP/6-31G+(d,p) level. The red
      shift of absorption maximum from unsubstituted pyrylium and thiopyrylium to
      dimethylamino-substituted pyrylium and thiopyrylium as well as the red shift seen
      in the pyrylium-thiopyrylium transformation is interpreted in terms of the
      molecular orbital theory.

PMID- 22582946
TI  - Single port laparoscopic surgery: concept and controversies of a new technique.
AB  - LESS, or laparo-endoscopic single site surgery, is a promising new method in
      minimally invasive surgery. An increasing number of surgical procedures are being
      performed using this technique; however, its large-scale adoption awaits results
      of prospective randomized controlled studies confirming potential benefits.
      Theoretically, cosmetic outcomes, postoperative pain and complication rates could
      be improved with use of single site surgery. This study describes introduction of
      the method in a private hospital in Denmark in which 40 women were treated for
      benign gynecologic conditions. Although the operations described are the first of
      their kind reported in Denmark, favorable operating times and very low
      complication rates are seen. It is the authors' opinion that in addition to being
      feasible for hysterectomy, single port laparoscopy may become the preferred
      method for many simple gynecological procedures.

PMID- 22582947
TI  - In vitro interactions of biological nucleophiles with fluorotelomer unsaturated
      acids and aldehydes: fate and consequences.
AB  - Fluorotelomer unsaturated aldehydes and acids (FTUALs and FTUCAs) are
      intermediate metabolites that form from the biotransformation of fluorotelomer
      based chemicals. FTUALs and FTUCAs have been previously suggested to contribute
      to the toxicity associated with human exposure to fluorotelomer compounds by
      covalently binding to biological nucleophiles. However, the extent of their
      reactivity has only been assessed with glutathione. The purpose of the present
      study was to assess the reactivity of these intermediate metabolites with a
      series of nucleophilic amino acids and model proteins. In vitro experiments were
      carried out in an aqueous buffer system to determine the reactivity of
      nucleophilic amino acids with FTUCAs and FTUALs having varying fluorinated chain
      lengths. Using (19)F NMR spectroscopy to monitor the disappearance of the FTUCAs
      and FTUAL signals and the production of a fluoride signal, reaction rate
      constants were determined under pseudo-first-order conditions. The FTUCAs reacted
      only with cysteine with the following second order rate constants: 3.63 (+/-
      1.37) * 10(-5) min(-1) mM(-1) (4:2 FTUCA), 1.19 (+/- 0.91) * 10(-5) min(-1) mM(
      1) (6:2 FTUCA), and 4.56 (+/- 0.94) * 10(-5) min(-1) mM(-1) (8:2 FTUCA). The
      FTUALs were significantly more reactive than any of the FTUCAs with reactivity
      decreasing in the following order: cysteine >> histidine > lysine >> arginine.
      The following second-order rate constants were obtained: 5.7 (+/- 4.2) * 10(-4)
      min(-1) mM(-1) (histidine), 4.3 (+/- 1.4) * 10(-4) min(-1) mM(-1) (lysine), and
      1.4 (+/- 0.73) * 10(-4) min(-1) mM(-1) (arginine). FTUCAs and FTUALs were also
      reacted with model proteins to assess their potential for forming covalent
      adducts. Electrospray ionization mass spectrometry (ESI-MS) was used to
      investigate the stoichiometry of FTUCAs and FTUALs covalently bound to
      apomyoglobin (ApoMg) and human serum albumin (HSA). FTUCAs were not reactive,
      whereas two measurable FTUAL adducts were formed with both ApoMg and HSA at each
      of the FTUAL chain lengths (6:2, 8:2, and 10:2). This is the first study to probe
      the reactivity of FTUALs and FTUCAs with nucleophiles other than glutathione,
      further elucidating possible FTUAL and FTUCA fate within biological systems.

PMID- 22582948
TI  - Presence of iron in segmented heterochromia of the scalp hair without iron
      deficiency anaemia.

PMID- 22582950
TI  - Master triathletes have not reached limits in their Ironman triathlon
      performance.
AB  - The purpose of this study was to analyze the participation and performance trends
      of male triathletes in the "Ironman Switzerland" from 1995 to 2010. Participation
      trends of all finishers aged between 18 and 64 years were analyzed over the 16
      year period by considering four 4-year periods 1995-1998, 1999-2002, 2003-2006,
      and 2007-2010, respectively. The 3.8-km swimming, 180-km cycling, 42-km running
      times, and total race times were analyzed for the top 10 triathletes in each age
      group from 18 to 64 years. The participation of master triathletes (>=40 years
      old) increased over the years, representing on average 23%, 28%, 37%, and 48% of
      total male finishers during the four 4-year periods, respectively. Over the 1995
      2010 period, triathletes older than 40 years significantly improved their
      performance in swimming, cycling, running, and in the total time taken to
      complete the race. The question whether master Ironman triathletes have yet
      reached limits in their performance during Ironman triathlon should be raised.
      Further studies investigating training regimes, competition experience, or socio
      demographic factors are needed to gain better insights into the phenomenon of the
      relative improvement in ultra-endurance performance with advancing age. 

PMID- 22582952
TI  - Living with difference: experiences of adolescent girls with cleft lip and
      palate.
AB  - OBJECTIVE: This study explored the experiences of adolescent girls with cleft lip
      and palate who were preparing for orthognathic surgery. DESIGN: A qualitative
      study, based on a phenomenological approach, explored adolescents' experiences.
      Two 1-hour semistructured interviews were conducted before surgery, and member
      checking was employed to verify findings with each participant. SETTING: A
      tertiary care pediatric hospital in central Canada. PARTICIPANTS: A criterion
      sampling technique was used to recruit a sample of seven participants with cleft
      lip and palate ranging in age from 15 to 20 years who were scheduled for cleft
      orthognathic surgery. RESULTS: PARTICIPANTS described experiencing teasing,
      bullying, and stares. In many cases, participants sought to resist and dismiss
      negative social attitudes about their visible difference while working to combat
      this with a positive view of who they really are. To varying degrees,
      participants felt constricted in engaging in the community as they were worried
      what others thought of their visible difference. They worked at finding ways to
      reduce the impact of social stigma through coping strategies, social supports,
      and reconstructive surgery. CONCLUSIONS: Adolescent girls can experience strain
      associated with living with a facial difference; however, they find strategies to
      cope with the perception of difference. Reconstructive surgery is viewed as a
      means to increase confidence. Further intervention is needed in understanding and
      addressing stigma and fostering resiliency related to female adolescents living
      with a facial difference.

PMID- 22582953
TI  - The journey to mandatory continuing education in Illinois.

PMID- 22582951
TI  - Protein substrate discrimination in the quiescin sulfhydryl oxidase (QSOX)
      family.
AB  - This work explores the substrate specificity of the quiescin sulfhydryl oxidase
      (QSOX) family of disulfide-generating flavoenzymes to provide enzymological
      context for investigation of the physiological roles of these facile catalysts of
      oxidative protein folding. QSOX enzymes are generally unable to form disulfide
      bonds within well-structured proteins. Use of a temperature-sensitive mutant of
      ubiquitin-conjugating enzyme 4 (Ubc4') as a model substrate shows that QSOX
      activity correlates with the unfolding of Ubc4' monitored by circular dichroism.
      Fusion of Ubc4' with the more stable glutathione-S-transferase domain
      demonstrates that QSOX can selectively introduce disulfides into the less stable
      domain of the fusion protein. In terms of intermolecular disulfide bond
      generation, QSOX is unable to cross-link well-folded globular proteins via their
      surface thiols. However, the construction of a septuple mutant of RNase A,
      retaining a single cysteine residue, demonstrates that flexible protein monomers
      can be directly coupled by the oxidase. Steady- and pre-steady-state kinetic
      experiments, combined with static fluorescence approaches, indicate that while
      QSOX is an efficient catalyst for disulfide bond formation between mobile
      elements of structure, it does not appear to have a significant binding site for
      unfolded proteins. These aspects of protein substrate discrimination by QSOX
      family members are rationalized in terms of the stringent steric requirements for
      disulfide exchange reactions.

PMID- 22582954
TI  - Credentialing: understanding the terms.
AB  - Credentialing is an umbrella term that encompasses several categories, many of
      which have an impact when considering professional development for registered
      nurses. This column identifies select categories within the credentialing domain.

PMID- 22582955
TI  - The journey to zero.
AB  - This column explores some of the strategies employed on a journey to zero central
      line infections.

PMID- 22582956
TI  - Role-play revisited.
AB  - This column provides tips for designing and implementing role-play.

PMID- 22582958
TI  - Redox-responsive regulation of denitrification genes in Brucella.
AB  - Brucella strains encounter oxygen deprivation during their intracellular
      replication in host cells, and the capacity of these bacteria to utilize NO(3) as
      an alternative electron acceptor for respiration plays an important role in their
      successful adaption to their intracellular niche. In this issue of Molecular
      Microbiology, Carrica et al (2012). report that NtrY and NtrX comprise a redox
      responsive two-component regulator in Brucella abortus 2308 that responds to
      decreasing levels of O(2) and induces the expression of this strain's
      denitrification genes. Thus, NtrYX joins the increasing number of genetic
      regulators that contribute to the metabolic versatility required for the
      virulence of Brucella strains in their mammalian hosts.

PMID- 22582959
TI  - Bright, color-tunable fluorescent dyes based on pi-expanded
      diketopyrrolopyrroles.
AB  - A synthetic approach to the structurally diverse family of pi-expanded
      diketopyrrolopyrroles is described. A three-step strategy appears to be very
      general and starts with the preparation of diketopyrrolopyrroles followed by N
      alkylation with bromoacetaldehyde diethyl acetal and electrophilic aromatic
      substitution. The final reaction regioselectively furnishes S-shaped, violet and
      blue functional dyes of previously unknown structure. New dyes possess sharp
      absorption and emission peaks, with very high molar absorption coefficients and
      reasonable fluorescence quantum yields. As a proof of principle, cell uptake of
      selected dye was demonstrated.

PMID- 22582960
TI  - Return of the metabolic trajectory to the original area after human bone marrow
      mesenchymal stem cell transplantation for the treatment of fulminant hepatic
      failure.
AB  - Our recent study first demonstrated that human bone marrow mesenchymal stem cell
      (hBMSC) transplantation could prevent death from fulminant hepatic failure (FHF)
      in pigs. To further clarify the metabolic mechanism of hBMSC transplantation in
      FHF, the plasma collected from FHF pigs that received transplantation of hBMSCs
      was examined using metabolic analysis to identify the key molecular markers that
      regulate recovery. The results showed that obvious metabolic disturbance occurred
      during FHF, whereas the hBMSC transplantation group showed less severe liver
      injury. The metabolic trajectory returns to its original state at week 3
      following the hBMSC transplantation. In total, the concentration of 26
      metabolites, including conjugated bile acids, phosphatidylcholines,
      lysophosphatidylcholines, fatty acids, amino acid and sphingomyelin, are
      significantly different between the FHF group and the hBMSC transplantation
      group. Moreover, the time course of changes in the metabolites corresponded with
      that of the biochemical and histological analyses. Real-time PCR further
      confirmed that the gene expression of phospholipase A1, lecithin-cholesterol
      acyltransferase and lysophosphatidylcholine acyltransferase 1 decreased
      significantly, whereas that of phospholipase A2 remained stable, which explains
      the decrease of the phosphatidylcholines and lysophosphatidylcholines. These
      novel results have revealed a metabolic mechanism for the hBMSC transplantation
      in FHF, which could lead to the future development of treatment strategies for
      stem cell therapies. 

PMID- 22582961
TI  - Effect of partial or complete elimination of light-harvesting complexes on the
      surface electric properties and the functions of cyanobacterial photosynthetic
      membranes.
AB  - Influence of the modification of the cyanobacterial light-harvesting complex
      [i.e. phycobilisomes (PBS)] on the surface electric properties and the functions
      of photosynthetic membranes was investigated. We used four PBS mutant strains of
      Synechocystis sp. PCC6803 as follows: PAL (PBS-less), CK (phycocyanin-less), BE
      (PSII-PBS-less) and PSI-less/apcE(-)  (PSI-less with detached PBS). Modifications
      of the PBS content lead to changes in the cell morphology and surface electric
      properties of the thylakoid membranes as well as in their functions, such as
      photosynthetic oxygen-evolving activity, P700 kinetics and energy transfer
      between the pigment-protein complexes. Data reveal that the complete elimination
      of PBS in the PAL mutant causes a slight decrease in the electric dipole moments
      of the thylakoid membranes, whereas significant perturbations of the surface
      charges were registered in the membranes without assembled PBS-PSII macrocomplex
      (BE mutant) or PSI complex (PSI-less mutant). These observations correlate with
      the detected alterations in the membrane structural organization. Using a
      polarographic oxygen rate electrode, we showed that the ratio of the fast to the
      slow oxygen-evolving PSII centers depends on the partial or complete elimination
      of light-harvesting complexes, as the slow operating PSII centers dominate in the
      PBS-less mutant and in the mutant with detached PBS.

PMID- 22582962
TI  - Use of continuous positive airway pressure during stabilisation and retrieval of
      infants with suspected bronchiolitis.
AB  - AIM: Infants with viral bronchiolitis are often hospitalised with a proportion
      requiring respiratory support. The aim of this review was to examine the use of
      nasal prong continuous positive airway pressure (CPAP) as a management strategy
      for infants with a diagnosis of bronchiolitis, who required stabilisation and
      transport to a tertiary centre. METHOD: A retrospective audit of infants with
      bronchiolitis requiring CPAP during transport between January 2003 and June 2007.
      RESULTS: Nasal CPAP was initiated in 54 infants with 51 of these (34 ex-preterm,
      17 term) subsequently continuing on CPAP during retrieval. Mean CPAP pressure was
      7 cmH(2)O. Oxygenation improved between stabilisation and the end of retrieval (P
      < 0.01). During retrieval, there was no significant increase in transcutaneous
      CO(2), no infant required endotracheal ventilation and no adverse events were
      noted. Five infants were intubated within the first 24 h of admission at the
      receiving hospital. CONCLUSION: This review demonstrated that use of nasal prong
      CPAP to transport infants with bronchiolitis was a safe management strategy in
      those with moderate to severe disease severity.

PMID- 22582963
TI  - Do stimulus--action associations contribute to repetition priming?
AB  - Despite evidence that response learning makes a major contribution to repetition
      priming, the involvement of response representations at the level of motor
      actions remains uncertain. Levels of response representation were investigated in
      4 experiments that used different tasks at priming and test. Priming for stimuli
      that required congruent responses across 2 tasks was compared with that for
      stimuli requiring incongruent responses. Congruent responses showed more priming
      than incongruent responses did when congruence involved both decisions and
      actions (Experiment 1), decisions only (Experiment 2), and actions only
      (Experiment 4) but not when decision and action congruence were set in opposition
      (Experiment 3). These results demonstrate response learning with response
      representations at the level of both decisions and actions.

PMID- 22582964
TI  - Serial recall, word frequency, and mixed lists: the influence of item
      arrangement.
AB  - Studies of the effect of word frequency in the serial recall task show that lists
      of high-frequency words are better recalled than lists of low-frequency words;
      however, when high- and low-frequency words are alternated within a list, there
      is no difference in the level of recall for the two types of words, and recall is
      intermediate between lists of pure frequency. This pattern has been argued to
      arise from the development of a network of activated long-term representations of
      list items that support the redintegration of all list items in a nondirectional
      and nonspecific way. More recently, it has been proposed that the frequency
      effect might be a product of the coarticulation of items at word boundaries and
      their influence on rehearsal rather than a consequence of memory representations.
      The current work examines recall performance in mixed lists of an equal number of
      high- and low-frequency items arranged in contiguous segments (i.e., HHHLLL and
      LLLHHH), under quiet and articulatory suppression conditions, to test whether the
      effect is (a) nondirectional and (b) dependent on articulatory processes. These
      experiments demonstrate that neither explanation is satisfactory, although the
      results suggest that the effect is mnemonic. A language-based approach to short
      term memory is favored with emphasis on the role of speech production processes
      at output.

PMID- 22582965
TI  - Inoculation against forgetting: advantages of immediate versus delayed initial
      testing due to superior verbatim accessibility.
AB  - In this study, potential benefits of early memory testing were examined in terms
      of "inoculating" eyewitness memory against forgetting. As predicted by fuzzy
      trace theory (e.g., Reyna & Titcomb, 1997), a larger testing advantage in the
      delayed recall of event details was expected after immediate testing than after
      delayed testing because of the decline in accessibility of verbatim traces over
      time. However, memory for only the gist of these details was expected to be
      relatively stable over time, resulting in a smaller (if any) effect of the timing
      of interpolated testing. After viewing a target event, participants were
      questioned about event items immediately, after a 24-hr delay, or after a 48-hr
      delay and were free to respond at either the gist or the verbatim level. Verbatim
      memory for event details was tested 72 hr after the event. As expected, immediate
      interpolated testing improved verbatim memory performance on the final test more
      than delayed testing did, yielding a larger testing effect. Furthermore, the
      effect of the timing of interpolated testing on the magnitude of the testing
      effect was mediated by verbatim accessibility at interpolated testing. In
      contrast, memory for only the gist of event details was unaffected by the timing
      of interpolated testing, both on the interpolated test and on the final test. The
      findings highlight the role of declining verbatim memory over time in accounting
      for the advantage of immediate over delayed interpolated testing in inoculating
      eyewitness memory against forgetting of detailed information.

PMID- 22582966
TI  - Rapid recollection of foresight judgments increases hindsight bias in a memory
      design.
AB  - One component of hindsight bias is memory distortion. This component is measured
      with a memory design, in which individuals answer questions, learn the correct
      answers, and recall their original answers. Hindsight bias occurs when
      participants' recollections are closer to the correct answers than their original
      judgments actually were. The present study used a memory design to examine the
      relationship between response time in recalling original answers and the
      magnitude of hindsight bias. In Experiment 1, participants' response times were
      negatively correlated with a hindsight bias index. In Experiment 2, half of the
      participants were instructed to recall their original judgments quickly and the
      other participants were instructed to take time to recall their judgments. The
      hindsight bias index was greater among rapidly responding participants than among
      delayed responding participants. These results, in conjunction with other
      findings, support a separate components view of hindsight bias. The memory
      distortion component of hindsight bias appears to occur quickly, and unbiased
      responding requires time for processing. This finding relates the memory
      distortion component of hindsight bias to other cognitive biases, such as the
      belief bias in syllogistic reasoning. The relationship of this hindsight bias
      component to dual-process models of cognition is discussed, and several avenues
      for additional research are suggested.

PMID- 22582967
TI  - Geometry three ways: an fMRI investigation of geometric information processing
      during reorientation.
AB  - The geometry formed by the walls of a room is known to be a potent cue in
      reorientation, yet little is known about the use of geometric information gleaned
      from other contexts. We used functional magnetic resonance imaging to examine
      neural activity in adults while reorienting in 3 different environments: the
      typical rectangular walled room, a rectangular configuration of pillars in an
      open field, and a rectangular floor in an open field. Behavioral response
      patterns for the 3 environments were similar, but pairwise contrasts of brain
      activation revealed differences at the neural level. We observed greater medial
      temporal lobe (MTL) involvement when reorienting with the pillars versus the
      walls and floor. In addition, the walled room selectively engaged areas of
      posterior parahippocampal cortex corresponding to the parahippocampal place area,
      when compared with the floor. Finally, a conjunction analysis of the 3 geometry
      conditions, compared with a control task, revealed activation in the primary
      auditory cortex that was common to all geometry conditions. These findings add to
      growing evidence that adults use verbal processes to encode environment geometry
      and that the reorientation tasks that young children find difficult are
      particularly hippocampus-dependent.

PMID- 22582968
TI  - When and why a failed test potentiates the effectiveness of subsequent study.
AB  - Teachers and trainers often try to prevent learners from making errors, but
      recent findings (e.g., Kornell, Hays, & Bjork, 2009) have demonstrated that tests
      can potentiate subsequent learning even when the correct answer is difficult or
      impossible to generate (e.g., "What is Nate Kornell's middle name?"). In 3
      experiments, we explored when and why a failed test enhances learning. We found
      that failed tests followed by immediate feedback produced greater retention than
      did a presentation-only condition. Failed tests followed by delayed feedback, by
      contrast, did not produce such a benefit-except when the direction of the final
      test was reversed (i.e., the participants were provided with the target and had
      to produce the original cue). Our findings suggest that generating an incorrect
      response to a cue both activates the semantic network associated with the cue and
      suppresses the correct response. These processes appear to have 2 consequences:
      If feedback is presented immediately, the semantic activation enhances the
      mapping of the cue to the correct response; if feedback is presented at a delay,
      the prior suppression boosts the learning of the suppressed response.

PMID- 22582969
TI  - A causal contiguity effect that persists across time scales.
AB  - The contiguity effect refers to the tendency to recall an item from nearby study
      positions of the just recalled item. Causal models of contiguity suggest that
      recalled items are used as probes, causing a change in the memory state for
      subsequent recall attempts. Noncausal models of the contiguity effect assume the
      memory state is unaffected by recall per se, relying instead on the correlation
      between the memory states at study and at test to drive contiguity. We examined
      the contiguity effect in a probed recall task in which the correlation between
      the study context and the test context was disrupted. After study of several
      lists of words, participants were given probe words in a random order and were
      instructed to recall a word from the same list as the probe. The results showed
      both short-term and long-term contiguity effects. Because study order and test
      order are uncorrelated, these contiguity effects require a causal contiguity
      mechanism that operates across time scales.

PMID- 22582970
TI  - Combination of cytarabine and topotecan in patients treated for acute myeloid
      leukemia with persistent disease after frontline induction.
AB  - After a first course of induction chemotherapy, 30-40% of patients with acute
      myeloid leukemia (AML) do not achieve a complete response (CR). A second course
      of an anthracycline and intermediate-dose cytarabine (IDAC) allows a significant
      number of patients with persistent AML at day 14 to finally achieve a CR. We
      hypothesized that use of a topotecan and cytarabine combination in this setting
      might improve tolerance and efficacy. Cytarabine (1000 mg/m(2)/12 h days 1-4) was
      combined with topotecan (TA, 1.25 mg/m(2)/day by continuous intravenous infusion
      [CIV] days 1-4) in 31 consecutive patients with >= 5% marrow blasts by day 14 of
      induction. The median follow-up was 36 months. The CR rate was 81%, and the 2
      year probability of overall survival and cumulative incidence of relapse were 66%
      and 38%, respectively. No unexpected toxicity was observed. Comparison with
      historical controls treated with the combination of a similar schedule of
      cytarabine and an anthracycline showed a better CR rate (p = 0.054), overall
      survival (p = 0.03) and cumulative incidence of relapse (p = 0.03). These results
      were confirmed in a multivariate analysis model. This work shows that the
      substitution of an anthracycline by topotecan is feasible and associated with
      significant efficacy for patients with AML with persistent leukemia at day 14
      after standard-dose anthracycline induction.

PMID- 22582971
TI  - Melatonin-induced autophagy is associated with degradation of MyoD protein in
      C2C12 myoblast cells.
AB  - MyoD is a muscle-specific transcriptional factor that acts as a master switch for
      skeletal muscle differentiation. This protein regulates myoblast proliferation
      and myogenic differentiation and is also a short-lived regulatory protein that is
      degraded by the ubiquitin system. However, the lysosomal pathway of MyoD protein
      degradation remains unknown. In this study, we sought to determine whether
      melatonin (1, 2mm)-induced autophagy causes the degradation of MyoD protein in
      C2C12 myoblast cells. Melatonin induced a significant increase in expression of
      the microtubule-associated protein 1 light chain 3 (LC3)-II and Beclin-1 proteins
      in a dose-dependent manner. Melatonin treatment also significantly increased p
      ERK, Ras, and p-Akt expressions in a dose-dependent manner. However, Bax
      expression was high compared with the absence of melatonin treatment, and Bcl-2
      expression was high in the 0.1-0.5mm melatonin treatments and low in the 1 and
      2mm melatonin treatments. Under the same conditions, cytosolic MyoD protein was
      significantly decreased in a dose-dependent manner and completely eliminated by
      36hr. This decrease in MyoD protein involved ubiquitin-mediated proteasomal
      activity with proteasome inhibitor MG132 or autophagy-dependent lysosomal
      degradation with lysosomal inhibitor bafilomycin A1 (Baf-A1). In the same
      condition, phosphorylation of the mammalian target of rapamycin, p-mTOR, and p
      S6K expression with Baf-A1 or Baf-A1-plus melatonin treatment were significantly
      decreased compared with the levels after treatment with melatonin only. Together,
      these results suggest that melatonin (1, 2mm)-induced autophagy results in
      partial lysosomal degradation of MyoD protein in C2C12 myoblast cells.

PMID- 22582972
TI  - Studies on the encapsulation of F- in single walled nanotubes of different
      chiralities using density functional theory calculations and Car-Parrinello
      molecular dynamics simulations.
AB  - In this study, the encapsulation of F(-) in different nanotubes (NTs) has been
      investigated using electronic structure calculations and Car-Parrinello molecular
      dynamics simulations. The carbon atoms in the single walled carbon nanotube (CNT)
      are systematically doped with B and N atoms. The effect of the encapsulation of
      F(-) in the boron nitride nanotube (BNNT) has also been investigated. Electronic
      structure calculations show that the (7,0) chirality nanotube forms a more stable
      endohedral complex (with F(-)) than the other nanotubes. Evidence obtained from
      the band structure of CNT calculations reveals that the band gap of the CNT is
      marginally affected by the encapsulation. However, the same encapsulation
      significantly changes the band gap of the BNNT. The density of states (DOS)
      derived from the calculations shows significant changes near the Fermi level. The
      snapshots obtained from the CPMD simulation highlight the fluctuation of the
      anion inside the tube and there is more fluctuation in BNNT than in CNT.

PMID- 22582973
TI  - Integrated virtual screening for the identification of novel and selective
      peroxisome proliferator-activated receptor (PPAR) scaffolds.
AB  - We describe a fully customizable and integrated target-specific "tiered" virtual
      screening approach tailored to identifying and characterizing novel peroxisome
      proliferator activated receptor gamma (PPARgamma) scaffolds. Built on structure-
      and ligand-based computational techniques, a consensus protocol was developed for
      use in the virtual screening of chemical databases, focused toward retrieval of
      novel bioactive chemical scaffolds for PPARgamma. Consequent from application,
      three novel PPAR scaffolds displaying distinct chemotypes have been identified,
      namely, 5-(4-(benzyloxy)-3-chlorobenzylidene)dihydro-2-thioxopyrimidine
      4,6(1H,5H)-dione (MDG 548), 3-((4-bromophenoxy)methyl)-N-(4-nitro-1H-pyrazol-1
      yl)benzamide (MDG 559), and ethyl 2-[3-hydroxy-5-(5-methyl-2-furyl)-2-oxo-4-(2
      thienylcarbonyl)-2,5-dihydro-1H-pyrrol-1-yl]-4-methyl-1,3-thiazole-5-carboxylate
      (MDG 582). Fluorescence polarization(FP) and time resolved fluorescence resonance
      energy transfer (TR-FRET) show that these compounds display high affinity
      competitive binding to the PPARgamma-LBD (EC(50) of 215 nM to 5.45 MUM).
      Consequent characterization by a TR-FRET activation reporter assay demonstrated
      agonism of PPARgamma by all three compounds (EC(50) of 467-594 nM). Additionally,
      differential PPAR isotype specificity was demonstrated through assay against
      PPARalpha and PPARdelta subtypes. This work showcases the ability of target
      specific "tiered screen" protocols to successfully identify novel scaffolds of
      individual receptor subtypes with greater efficacy than isolated screening
      methods.

PMID- 22582974
TI  - High frequency tympanometry findings in neonates: does it depend on head
      position?
AB  - OBJECTIVE: The purpose of this study was to investigate the effect of head
      positions on high frequency tympanometry (HFT) results obtained from neonates.
      DESIGN: A cross-sectional study to compare HFT results obtained from neonates in
      two head positions (face sideways and face up). STUDY SAMPLE: One hundred and
      fifty-seven neonates (80 female, 77 male; mean age = 48.3 +/- 26.7 hours)
      participated. RESULTS: The mean uncompensated admittance at 200 daPa obtained in
      the face sideways position was significantly greater than that obtained in the
      face up position (1.02 versus 0.96 mmho). A significant ear effect for baseline
      compensated admittance was found (right/left = 0.64/0.53 mmho). However, there
      were no significant main effects for head positions for the tympanometric peak
      pressure, baseline compensated static admittance, and component compensated
      static admittance measures, indicating that these measures are resilient to head
      positions. CONCLUSION: These findings support the use of HFT normative values
      regardless of the two head positions investigated in the present study.

PMID- 22582975
TI  - The influence of transforming growth factor-alpha, cyclooxygenase-2, matrix
      metalloproteinase (MMP)-7, MMP-9 and CXCR4 proteins involved in epithelial
      mesenchymal transition on overall survival of patients with gastric cancer.
AB  - AIMS: Determination of prognostic parameters that are predictive of survival of
      gastric cancer (GC) may allow better identification of patients who could benefit
      from current chemotherapy regimens. To assess the correlation between tumour
      progression and epithelial-mesenchymal transition (EMT), we assayed the
      expression levels of selected molecules involved in EMT [CD44, transforming
      growth factor (TGF)-alpha, cyclooxygenase-2 (COX-2), matrix metalloproteinase
      (MMP)-7, MMP-9 and C-X-C chemokine receptor (CXCR4)], and correlated these with
      overall patient survival (OS) and disease stage. METHODS AND RESULTS: Medical
      records and pathological biopsy results of 137 patients with GC were evaluated
      retrospectively. Spearman's correlation analysis showed that expression of CXCR4
      was correlated significantly with the expression of all other proteins studied.
      In contrast, COX-2 expression correlated significantly with the expression of
      only MMP-7 (P = 0.011), MMP-9 (P = 0.015) and CXCR4 (P = 0.013). We observed
      significant negative correlations between OS and the expression of TGF-alpha (P =
      0.017), COX-2 (P < 0.001), CXCR4 (P = 0.010), MMP-7 (P = 0.020) and MMP-9 (P =
      0.015). On multivariate analysis, only COX-2 was an independent prognostic factor
      for OS [hazard ratio (HR) = 3.34; 95% confidence interval (CI): 1.43-9.75; P =
      0.002). CONCLUSIONS: COX-2, TGF-alpha, MMP-7, MMP-9 and CXCR4 are associated with
      poor OS in gastric cancer.

PMID- 22582976
TI  - Understanding fluxes as media for directed synthesis: in situ local structure of
      molten potassium polysulfides.
AB  - Rational exploratory synthesis of new materials requires routes to discover novel
      phases and systematic methods to tailor their structures and properties.
      Synthetic reactions in molten fluxes have proven to be an excellent route to new
      inorganic materials because they promote diffusion and can serve as an additional
      reactant, but little is known about the mechanisms of compound formation, crystal
      precipitation, or behavior of fluxes themselves at conditions relevant to
      synthesis. In this study we examine the properties of a salt flux system that has
      proven extremely fertile for growth of new materials: the potassium polysulfides
      spanning K(2)S(3) and K(2)S(5), which melt between 302 and 206  degrees C. We
      present in situ Raman spectroscopy of melts between K(2)S(3) and K(2)S(5) and
      find strong coupling between n in K(2)S(n) and the molten local structure,
      implying that the S(n)(2-) chains in the crystalline state are mirrored in the
      melt. In any reactive flux system, K(2)S(n) included, a signature of changing
      species in the melt implies that their evolution during a reaction can be
      characterized and eventually controlled for selective formation of compounds. We
      use in situ X-ray total scattering to obtain the pair distribution function of
      molten K(2)S(5) and model the length of S(n)(2-) chains in the melt using reverse
      Monte Carlo simulations. Combining in situ Raman and total scattering provides a
      path to understanding the behavior of reactive media and should be broadly
      applied for more informed, targeted synthesis of compounds in a wide variety of
      inorganic fluxes.

PMID- 22582978
TI  - Spatial and temporal nature of reactive oxygen species production and programmed
      cell death in elm (Ulmus pumila L.) seeds during controlled deterioration.
AB  - Seed deterioration is poorly understood and remains an active area for research.
      Seeds of elm (Ulmus pumila L.) were aged at 37  degrees C above water [controlled
      deterioration treatment (CDT)] for various lengths of time to assess programmed
      cell death (PCD) and reactive oxygen species (ROS) product in embryonic tissues
      during a 5 d period. The hallmarks of PCD were identified in the elm seeds during
      CDT including TUNEL experiments, DNA laddering, cytochrome c (cyt c) leakage and
      enzymatic activities. These analyses indicated that PCD occurred systematically
      and progressively in deteriorated elm seeds. Cyt c release and increase in
      caspase-3-like/DEVDase activity occurred during CDT, which could be suppressed by
      ascorbic acid (AsA) and caspase-3 inhibitor Ac-DEVD-CHO, respectively. In situ
      localization of ROS production indicated that the distinct spatial-temporal
      signature of ROS during CDT coincided with the changes in PCD hallmark features.
      Multiple antioxidant elements were activated during the first few days of CDT,
      but were subsequently depleted as PCD progressed. Taken together, our findings
      identify PCD as a key mechanism that occurs asymmetrically during elm seeds CDT
      and suggest an important role for PCD in seeds deterioration.

PMID- 22582977
TI  - Histological diagnosis and evaluation of the Swede score colposcopic system in a
      large cohort of pregnant women with atypical cervical cytology or cervical
      malignancy signs.
AB  - OBJECTIVE: We evaluated the distribution of histological diagnoses in pregnant
      women with atypical cytology or cervical malignancy signs, as well as the
      usefulness of the Swede score colposcopic scoring system to reduce the need for
      diagnostic cervical biopsy. DESIGN: Prospective clinical study. SETTING AND
      POPULATION: The study comprised 261 pregnant women undergoing colposcopic
      investigation because of atypical cervical cytology, dysplastic biopsy changes,
      recurrent non-obstetric bleeding or pathological appearance of the cervix.
      METHODS: Five colposcopic variables (acetowhiteness, margins plus surface, vessel
      patterns, lesion size and iodine staining) were scored with 0, 1 or 2 points.
      Colposcopically directed biopsies or loop electrosurgical excision biopsies were
      taken from all lesions. Histology was compared with the colposcopic score.
      Sensitivity and specificity were calculated for each variable, and the
      combination of all five variables, with high-grade lesions (i.e. cervical
      intraepithelial neoplasia (CIN2, CIN3 or adenocarcinoma-in-situ (AIS)) as
      endpoints. MAIN OUTCOME MEASURES: Colposcopic score (Swede score) and histology
      (CIN1, 2, 3; AIS; cancer). RESULTS: The specimens consisted of normal tissue in
      19.5% of cases, low-grade lesions (i.e. CIN1, koilocytosis, glandular dysplasia
      of lower grade than AIS) in 26.1%, high grade lesions in 52.9% and cancer in
      1.5%. All high grade lesions and cancers had total Swede scores of >= 5 and >= 8,
      respectively. Vessel patterns, lesion size and margins plus surface were most
      important for high grade lesion detection. CONCLUSION: The Swede score seems to
      be a useful tool in evaluating atypical cervical cytology in pregnant women and
      may reduce the need for diagnostic biopsies.

PMID- 22582979
TI  - Cassava starch-based films plasticized with sucrose and inverted sugar and
      reinforced with cellulose nanocrystals.
AB  - Bionanocomposites films of cassava starch plasticized with sucrose and inverted
      sugar and reinforced by cellulose nanocrystals (CNCs) were prepared by solution
      casting method incorporating 0.1 to 5 wt% of eucalyptus CNCs. The nanocrystals
      were characterized using transmission electron microscopy, whereas the
      bionanocomposites properties were studied using Fourier transform infrared
      spectroscopy, tensile measurements, water solubility, swelling behavior, and
      water activity (a(w)). The water resistance properties (solubility and swelling
      behavior) of the nanocomposites were enhanced with the addition of cellulose
      nanofillers. These results were explained in terms of the high crystallinity of
      the nanocrystals and the formation of a rigid network with the nanofillers, which
      provide physical barriers to the permeation of water within the hydrophilic
      cassava matrix. The addition of CNCs in the bionanocomposites decreases a(w)
      linearly, reaching values below 0.5 (for CNCs concentration higher than 4 wt%), a
      reference value for no microbial proliferation for food product design. The
      presence of small concentrations of CNCs (0.1-0.3 wt%) also effectively increased
      the maximum tensile strength (more than 90%) and elastic modulus (more than
      400%), indicating the formation of a suitable percolation network in this
      concentration range. Because the cellulose nanofillers enhanced the mechanical
      and water stability properties of the nanocomposites, the obtained results in
      this work may be applied to the development of biodegradable packaging or
      coatings to enhance shelf life of food products. PRACTICAL APPLICATION: The main
      drawbacks of using starch-based polymers as packaging or coating in the food
      industry are their low mechanical properties and inherent water sensitivity. This
      study demonstrates that cellulose nanocrystals can be used to: (i) obtain better
      mechanical properties (increasing the tensile strength and modulus more than 90%
      and 400%, respectively; (ii) enhance the water stability and (iii) water activity
      of starch-based films. These results indicate that the obtained environmentally
      friendly nanocomposites in this work can be used to the development of films or
      coatings to enhance the shelf life of food products.

PMID- 22582980
TI  - Genetic predisposition to atorvastatin-induced myopathy: a case report.
AB  - WHAT IS KNOWN AND OBJECTIVE: The major clinical complication of statins is a
      variety of muscle complaints ranging from myalgia to rhabdomyolysis. There is
      growing evidence that carriers of genetic polymorphisms in the enzymes and
      transporters implicated in statin disposition, particularly the SLCO1B1 gene, are
      at increased risk of myotoxicity. Our objective is to report on two cases of
      statin-induced myopathy occurring in a family with two patients who are carriers
      of the loss of function SLCO1B1 genetic variant and to briefly review the related
      literature. CASE SUMMARY: Patient 1, a 48-year-old man with history of coronary
      artery disease, experienced rapidly evolving muscle pain and weakness of the
      extremities during treatment with atorvastatin 40 mg. Patient 2, a 65-year-old
      man, father of patient 1, had symptoms similar to those of his son after 2 weeks'
      treatment with the same statin. Atorvastatin was stopped in both cases, and
      symptoms resolved. On the basis of family relationship between the two patients,
      it was possible to hypothesize a genetic basis for the myopathy. Genotyping
      showed the patients to be carriers of the rs4363657 polymorphism of SLCO1B1 gene.
      WHAT IS NEW AND CONCLUSION: The two cases reported here and the brief literature
      review emphasize the impact of genetic factors on the risk of myopathy with
      statins. Although genotyping all patients before initiating therapy is not
      recommended at present, pharmacogenetic testing may be useful for new patients
      who have a family history of statin-induced myopathy.

PMID- 22582981
TI  - Gradual increase in the risk of match injury in Norwegian male professional
      football: a 6-year prospective study.
AB  - The aim of this study was to monitor injury incidence and pattern in Norwegian
      male professional football over six consecutive seasons and compare the risk of
      injury between the preseason and competitive season. All time loss injuries were
      recorded by the medical staff of each club. In total, 2365 injuries were
      recorded. The incidence of acute injuries was 15.9/1000 match hours [95%
      confidence interval (CI): 14.9-16.8], 1.9/1000 training hours (95% CI: 1.7-2.0),
      and 1.4 (95% CI: 1.3-1.5) overuse injuries/1000 h. A linear regression model
      found an annual increase of 1.06 acute match injuries/1000 h (95% CI: 0.40-1.73),
      corresponding to a total increase of 49% during the 6-year study period. When
      accounting for interteam variation and clustering effects using a general
      estimating equation model, the increase in injury incidence was 0.92 (95% CI: 
      0.11-1.95, P = 0.083). No difference in the risk of acute match injuries (rate
      ratio (RR): 0.86, 95% CI: 0.73-1.01), acute training injuries (RR: 1.16, 95% CI:
      0.99-1.36), or overuse injuries (RR: 1.04, 95% CI: 0.89-1.21) was observed
      between the preseason and competitive season. In conclusion, the overall risk of
      acute match injuries in Norwegian male professional football increased by 49%
      during the study period, although this increase was not fully consistent across
      teams. We detected no change in the risk of training and overuse injuries or any
      difference between the preseason and competitive season. 

PMID- 22582982
TI  - Self-tracking: better medicine through pattern recognition.

PMID- 22582985
TI  - Antioxidant and antimicrobial activities of aporphinoids and other alkaloids from
      the bark of Annona salzmannii A. DC. (Annonaceae).
AB  - The antioxidant capacity by oxygen radical absorbance capacity (ORAC)-FL method
      and antimicrobial activity using the broth microdilution method of aporphinoids
      (liriodenine 1, anonaine 2 and asimilobine 3) and other alkaloids (reticuline 4
      and cleistopholine 5) isolated from the bark of Annona salzmannii A. DC.
      (Annonaceae) were evaluated. For antioxidant activity, the most active alkaloid
      was asimilobine with ORAC value of 2.09 relative trolox equivalents. For
      antimicrobial activity, some alkaloids showed significant minimal inhibitory
      concentration (MIC) values in the range of 25-100 ug mL(-1). The most active
      compounds were the aporphinoids liriodenine, anonaine and asimilobine, some of
      them more active than the positive control.

PMID- 22582987
TI  - Vulnerability of recently recharged groundwater in principal [corrected] aquifers
      of the United States to nitrate contamination.
AB  - Recently recharged water (defined here as <60 years old) is generally the most
      vulnerable part of a groundwater resource to nonpoint-source nitrate
      contamination. Understanding at the appropriate scale the interactions of natural
      and anthropogenic controlling factors that influence nitrate occurrence in
      recently recharged groundwater is critical to support best management and policy
      decisions that are often made at the aquifer to subaquifer scale. New logistic
      regression models were developed using data from the U.S. Geological Survey's
      National Water-Quality Assessment (NAWQA) program and National Water Information
      System for 17 principal aquifers of the U.S. to identify important source,
      transport, and attenuation factors that control nonpoint source nitrate
      concentrations greater than relative background levels in recently recharged
      groundwater and were used to predict the probability of detecting elevated
      nitrate in areas beyond the sampling network. Results indicate that dissolved
      oxygen, crops and irrigated cropland, fertilizer application, seasonally high
      water table, and soil properties that affect infiltration and denitrification are
      among the most important factors in predicting elevated nitrate concentrations.
      Important differences in controlling factors and spatial predictions were
      identified in the principal aquifer and national-scale models and support the
      conclusion that similar spatial scales are needed between informed groundwater
      management and model development.

PMID- 22582986
TI  - The role of dialectical self and bicultural identity integration in psychological
      adjustment.
AB  - OBJECTIVE: We applied the concept of naive dialecticism (Peng & Nisbett, ), which
      characterizes East Asians' greater tendency to encompass contradictory, ever
      changing, and interrelated features of an entity, to bicultural contexts and
      examined its effects on psychological well-being across various acculturating
      groups. METHOD: We administered questionnaire measures of the dialectical self,
      bicultural identity integration (BII; Benet-Martinez & Haritatos, 2005), and well
      being to Hong Kong Chinese (N = 213) in Study 1 and Mainland Chinese (N = 239) in
      Study 2. In Study 3, a 4-week longitudinal study was conducted among Hong Kong
      Chinese (N = 173) to test the relationships of these variables over time. We then
      extended similar measures to new immigrants from Mainland China (N = 67) in Study
      4 and Filipino domestic workers in Hong Kong (N = 153) in Study 5. RESULTS: Five
      studies converged to show that psychological adjustment was positively related to
      BII, but negatively related to the dialectical self. In Studies 1-3, dialecticism
      mediated the effect of BII on psychological adjustment among Hong Kong and
      Mainland Chinese bicultural individuals. CONCLUSIONS: Our findings reveal the
      deleterious effects of tolerance for contradiction on well-being and
      differentiate biculturalism patterns of immigration-based and globalization-based
      acculturation.

PMID- 22582988
TI  - A comprehensive proteome of Mycoplasma genitalium.
AB  - Mycoplasma genitalium is a human pathogen associated with several sexually
      transmitted diseases. Proteomic technologies, along with other methods for global
      gene expression analysis, play a key role in understanding the mechanisms of
      bacterial pathogenesis and physiology. The proteome of M. genitalium, model of a
      minimal cell, has been extended using a combination of different proteomic
      approaches and technologies. The total proteome of this microorganism has been
      analyzed using gel-based and gel-free approaches, achieving the identification of
      85.3% of the predicted ORFs. In addition, a comprehensive analysis of membrane
      subproteome has been performed. For this purpose, the TX-114 soluble fraction has
      been analyzed as well as the surface proteins, using cell-surface protein
      labeling with CyDye. Finally, the serological response of M. genitalium-infected
      patients and healthy donors has been analyzed to identify proteins that trigger
      immunological response. Here, we present the most extensive M. genitalium
      proteome analysis (85.3% of predicted ORFs), a comprehensive M. genitalium
      membrane analysis, and a study of the human serological response to M.
      genitalium. 

PMID- 22582989
TI  - A large increase in IAA during development of rice grains correlates with the
      expression of tryptophan aminotransferase OsTAR1 and a grain-specific YUCCA.
AB  - The indole-3-acetic acid (IAA) content of developing grains of Oryza sativa
      subsp. japonica was measured by combined liquid chromatography, tandem mass
      spectrometry in multiple-reaction-monitoring mode. The increase from 50 ng g(-1) 
      fresh weight to 2.9 ug g(-1)  fresh weight from 1 to 14 days after pollination
      was much larger than that previously reported by enzyme-linked immunoassay
      methods. The largest increase in IAA content coincided with the start of the
      major starch deposition phase of grain-fill. The increase in IAA content was
      strongly correlated with the expression of putative IAA biosynthesis genes,
      OsYUC9, OsYUC11 and OsTAR1, measured by quantitative reverse transcriptase
      polymerase chain reaction. These results confirm the importance of the tryptophan
      aminotransferase/YUCCA pathway in this system. All three genes were expressed in
      endosperm; expression of OsYUC11 appeared to be confined to endosperm tissue.
      Phylogenetic analysis indicated that OsYUC11 and AtYUC10 belong to a separate
      clade of YUCCAs, which do not have orthologues outside the Angiosperms. This
      clade may have evolved with a specific role in endosperm. Expression of
      tryptophan decarboxylase in developing rice grains did not correlate with IAA
      levels, indicating that tryptamine is unlikely to be important for IAA synthesis
      in this system. In light of these observations, we hypothesize that IAA
      production in developing rice grains is controlled via expression of OsTAR1,
      OsYUC9, OsYUC11 and that IAA may be important during starch deposition in
      addition to its previously suggested role early in grain development.

PMID- 22582990
TI  - Characteristics of physicians, their migration patterns and distance: a
      longitudinal study in Hiroshima, Japan.
AB  - INTRODUCTION: Although some characteristics of physicians are known to be
      associated with their recruitment in rural and remote areas, the factors that
      predict mobility of physicians, and in particular, their mobility to rural and
      distant areas are largely unknown. METHODS: Flows of all physicians (n=4268)
      among municipalities in Hiroshima Prefecture, Japan, between 2002 and 2008 were
      analysed. Physician data were obtained from the National Physician Census.
      Municipality-level population data derived from the National Basic Resident
      Register were merged with the physician data. Information on the road distances
      of two municipalities measured with a geographic information system (GIS) was
      added to the physician cohort. RESULTS: During the period of study, 24.8% of
      physicians crossed municipal borders, and among them, 66.6% moved distances of
      less than 60 min travel time. The number of migrated physicians decreased as the
      distance increased, which held true for both migration to urban and rural areas.
      In the univariate analysis, female, younger, and hospital physicians were more
      mobile to rural areas than were male, older, and clinic physicians. Male and
      younger (&&num;8804;40 years) physicians moved a longer distance than female and
      older physicians. Multivariate analysis revealed that age was a negative
      predictor (odds ratio [OR] per 10 years 0.62, 95% confidence interval [CI] 0.55
      0.70]), and affiliation with a hospital was a positive predictor of migration to
      rural areas (OR 6.19 [95% CI 4.21-9.10]). Male sex (OR 1.67 [95% CI 1.11-2.50])
      and hospital affiliation (OR 5.61 [95% CI 3.33-9.45]) were positive predictors,
      and age (OR per 10 years 0.39 [95% CI 0.33-0.46]) was a negative predictor of
      migrating a long distance. CONCLUSION: In order to attract physicians to rural
      and remote areas, health workforce policies need to set a target population of
      physicians who are highly mobile to such places. Combining known predictors of
      rural practice, such as physicians with rural background and primary care
      physicians, and the mobility predictors shown in this study (ie young, hospital
      and male physicians) would make the target more appropriate and policies more
      effective.

PMID- 22582991
TI  - Structure-activity relationship (SAR) study of ethyl 2-amino-6-(3,5
      dimethoxyphenyl)-4-(2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (CXL017) and
      the potential of the lead against multidrug resistance in cancer treatment.
AB  - Multidrug resistance (MDR) against standard therapies poses a serious challenge
      in cancer treatment, and there is a clinical need for new anticancer agents that
      would selectively target MDR malignancies. Our previous studies have identified a
      4H-chromene system, CXL017 (4) as an example, that can preferentially kill MDR
      cancer cells. To further improve its potency, we have performed detailed
      structure-activity relationship (SAR) studies at the 3, 4, and 6 positions of the
      4H-chromene system. The results reveal that the 3 and 4 positions prefer rigid
      and hydrophobic functional groups while the 6 position prefers a meta or para
      substituted aryl functional group and the substituent should be small and
      hydrophilic. We have also identified and characterized nine MDR cancer cells that
      acquire MDR through different mechanisms and demonstrated the scope of our new
      lead, 9g, to selectively target different MDR cancers, which holds promise to
      help manage MDR in cancer treatment.

PMID- 22582992
TI  - Dietary combination of fish oil and taurine decreases fat accumulation and
      ameliorates blood glucose levels in type 2 diabetic/obese KK-A(y) mice.
AB  - n-3 Polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA), and taurine are functional compounds abundantly
      present in seafoods. In this study, we examined the combined effects of EPA- and
      DHA-rich fish oil and taurine on white adipose tissue (WAT) weight and blood
      glucose levels in diabetic/obese KK-A(y)  mice. After a 4-wk administration of
      experimental diets (soybean oil or fish oil, supplemented with 0%, 2%, or 4%
      taurine), the increase in WAT weight of the mice fed the "fish oil + 4% taurine"
      diet was significantly suppressed compared to the "soybean oil + 4% taurine" and
      "fish oil only" diets. Serum triglycerides, free fatty acids, and total
      cholesterol levels decreased by fish oil administration. In addition, fish oil
      and taurine increased the activity of acyl-CoA oxidase, which is the rate
      limiting enzyme of peroxisomal beta-oxidation, increased in the liver of KK-A(y) 
      mice. The activity of fatty acid synthase decreased by fish oil diets.
      Furthermore, blood glucose and insulin levels were significantly lower in the
      mice fed fish oil than in the soybean oil-fed mice. In fish oil + 4% taurine
      group, hyperglycemia and hyperinsulinemia were effectively improved in KK-A(y) 
      mice compared to the fish oil only groups. In particular, the combination of fish
      oil and taurine enhanced the glucose transporter 4 (GLUT4) distribution in the
      plasma membrane of muscle tissue. These results suggest that EPA- and DHA-rich
      fish oil, especially in combination with taurine, exhibits preventive effects on
      WAT weight gain and hyperglycemia in diabetic/obese KK-A(y)  mice.

PMID- 22582994
TI  - Resolving the kinetics of lipid, protein and peptide diffusion in membranes.
AB  - Recent developments in the understanding of molecular diffusion phenomena in
      membranes are reviewed. Both model bilayers and biological membranes are
      considered in respect of lateral diffusion, rotational diffusion and transverse
      diffusion (flip-flop). For model systems, particular attention is paid to recent
      data obtained using surface-specific techniques such as sum frequency generation
      vibrational spectroscopy on supported lipid bilayers, and fluorescence
      correlation spectroscopy on giant unilamellar vesicles, both of which have
      yielded new insights into the intrinsic rates of diffusion and the energetic
      barriers to processes such as lipid flip-flop. Advances in single-molecule and
      many-molecule fluorescence methodologies have enabled the observation of
      processes such as anomalous diffusion for some membrane species in biological
      membranes. These are discussed in terms of new models for the role of membrane
      interactions with the cytoskeleton, the effects of molecular crowding in
      membranes, and the formation of lipid rafts. The diffusion of peptides, proteins
      and lipids is considered, particularly in relation to the means by which
      antimicrobial peptide activity may be rationalized in terms of membrane poration
      and lipid flip-flop.

PMID- 22582995
TI  - Factors influencing child mental health: A state-wide survey of Victorian
      children.
AB  - AIMS: This study aims to estimate the prevalence of mental health problems among
      Victorian children and to investigate factors associated with poorer mental
      health. METHOD: Computer-assisted telephone interviews were undertaken with the
      parents of 3370 randomly selected Victorian children aged 4 to 12 years. They
      reported on their child's mental health and special health-care needs as well as
      their own mental health, family functioning and a range of community and socio
      demographic variables. Population estimates and odds ratios (OR) were calculated
      with 95% confidence intervals (95% CI). RESULTS: Overall, 11.6% (95% CI = 10.3
      12.9%) of Victorian children were estimated to be at risk of having mental health
      problems. Factors independently placing children at increased risk of mental
      health problems that were 'of concern' include a child having special health-care
      needs (OR = 7.89, 95% CI 5.16 to 12.08), unhealthy family functioning (OR = 3.84,
      95% CI 2.19 to 6.74), parental mental health problems (OR = 7.89, 95% CI 5.16 to
      12.08), neighbourhood safety (OR = 2.47, 95% CI 1.20 to 5.07) and area of
      residence (OR = 2.01, 95% CI 1.33 to 3.02). CONCLUSIONS: A significant proportion
      of Victorian children are at some risk of mental health problems. These limited
      but important predictors of children's mental health reinforce the need for
      policy solutions that will extend beyond those offered by traditional mental
      health service systems.

PMID- 22582996
TI  - Professionalism in practice.

PMID- 22582997
TI  - Photosynthetic limitations and volatile and non-volatile isoprenoids in the
      poikilochlorophyllous resurrection plant Xerophyta humilis during dehydration and
      rehydration.
AB  - We investigated the photosynthetic limitations occurring during dehydration and
      rehydration of Xerophyta humilis, a poikilochlorophyllous resurrection plant, and
      whether volatile and non-volatile isoprenoids might be involved in desiccation
      tolerance. Photosynthesis declined rapidly after dehydration below 85% relative
      water content (RWC). Raising intercellular CO(2)  concentrations during
      desiccation suggest that the main photosynthetic limitation was photochemical,
      affecting energy-dependent RuBP regeneration. Imaging fluorescence confirmed that
      both the number of photosystem II (PSII) functional reaction centres and their
      efficiency were impaired under progressive dehydration, and revealed the
      occurrence of heterogeneous photosynthesis during desiccation, being the basal
      leaf area more resistant to the stress. Full recovery in photosynthetic
      parameters occurred on rehydration, confirming that photosynthetic limitations
      were fully reversible and that no permanent damage occurred. During desiccation,
      zeaxanthin and lutein increased only when photosynthesis had ceased, implying
      that these isoprenoids do not directly scavenge reactive oxygen species, but
      rather protect photosynthetic membranes from damage and consequent denaturation.
      X. humilis was found to emit isoprene, a volatile isoprenoid that acts as a
      membrane strengthener in plants. Isoprene emission was stimulated by drought and
      peaked at 80% RWC. We surmise that isoprene and non-volatile isoprenoids
      cooperate in reducing membrane damage in X. humilis, isoprene being effective
      when desiccation is moderate while non-volatile isoprenoids operate when water
      deficit is more extreme.

PMID- 22582998
TI  - "Click"-functionalization of [60]fullerene and graphene with an unsymmetrically
      functionalized diketopyrrolopyrrole (DPP) derivative.
AB  - A synthetic strategy is developed that allows for the facile functionalization of
      carbon nanostructures thus providing the possibility of comparing the striking
      different optical and electrochemical properties of ensembles based on the
      diketopyrrolopyrrole (DPP) chromophore covalently attached to either
      [60]fullerene or graphene.

PMID- 22582999
TI  - Decreasing incidence of placental abruption in Finland during 1980-2005.
AB  - OBJECTIVE: To study the incidence trends of placental abruption. DESIGN: Register
      based retrospective study. SETTING: The Finnish Medical Birth Register and
      Hospital Discharge Register. POPULATION: A total of 6231 placental abruption
      cases among 1 576 051 deliveries. METHODS: Data on demographic and pregnancy and
      delivery associated outcomes were collected. Data on overall incidence and
      maternal age were available 1980-2005. Data on other variables were available
      1987-2005. MAIN OUTCOME MEASURE: Placental abruption RESULTS: The overall
      incidence of placental abruption was 395/100 000 (0.4%). The incidence decreased
      31%, from 487/100 000 in 1980 to 337/100 000 in 2005 (p < 0.001). The incidence
      was lowest among women aged 20-24 years (305/100 000) and highest among women
      aged >=45 years (1309/100 000). During 1987-2005 the incidence was lowest among
      women with one or two deliveries (353/100 000) and highest in nulliparous women
      (382/100 000) and in women with three or more deliveries (595/100 000). The
      incidence was nearly double (577/100 000) among smoking compared with non-smoking
      women (341/100 000). The incidence was highest between gestational weeks 26 and
      29. Among newborns weighing <1500 g the incidence was higher (5734/100 000) than
      among those weighing >=2500 g (251/100 000). The incidence was higher in multiple
      (903/100 000) than in singleton pregnancies (374/100 000). CONCLUSION: The
      incidence of placental abruption decreased during 1980-2005. The incidence was
      highest among women aged 45 years or more, multiparous and smoking women, in
      multiple pregnancies and in women with low birthweight newborns.

PMID- 22583000
TI  - Research on the hypersensitive response.

PMID- 22583001
TI  - De novo synthesis of 1,4-dihydropyridines and pyridines.
AB  - An efficient and general method for the synthesis of 1,4-dihydropyridines and
      pyridines based on a lithiation/isomerization/intramolecular carbolithiation
      sequence is reported. This procedure provides an efficient, divergent, and
      straightforward entry to a wide range of polysubstituted dihydropyridines and
      pyridines starting from readily available N-allyl-ynamides.

PMID- 22583002
TI  - Electrogenerated chemiluminescence behavior of graphite-like carbon nitride and
      its application in selective sensing Cu2+.
AB  - This paper reports for the first time the electrogenerated chemiluminescence
      (ECL) behavior of graphite-like carbon nitride (g-C(3)N(4)) with K(2)S(2)O(8) as
      the coreactant. The possible ECL reaction mechanisms are proposed. The spectral
      features of the ECL emission and photoluminescence (PL) of g-C(3)N(4) are
      compared, and their resemblance demonstrates that the excited states of g
      C(3)N(4) from both ECL and photoexcitation are the same. The effects of
      K(2)S(2)O(8) concentration, pH, g-C(3)N(4)/carbon powder ratio, and scan rate on
      the ECL intensity have been studied in detail. Furthermore, it is observed that
      the ECL intensity is efficiently quenched by trace amounts of Cu(2+). g-C(3)N(4)
      is thus employed to fabricate an ECL sensor which shows high selectivity to
      Cu(2+) determination. The limit of detection is determined as 0.9 nM. It is
      anticipated that g-C(3)N(4) could be a new class of promising material for
      fabricating ECL sensors.

PMID- 22582993
TI  - Organotypic liver culture models: meeting current challenges in toxicity testing.
AB  - Prediction of chemical-induced hepatotoxicity in humans from in vitro data
      continues to be a significant challenge for the pharmaceutical and chemical
      industries. Generally, conventional in vitro hepatic model systems (i.e. 2-D
      static monocultures of primary or immortalized hepatocytes) are limited by their
      inability to maintain histotypic and phenotypic characteristics over time in
      culture, including stable expression of clearance and bioactivation pathways, as
      well as complex adaptive responses to chemical exposure. These systems are less
      than ideal for longer-term toxicity evaluations and elucidation of key cellular
      and molecular events involved in primary and secondary adaptation to chemical
      exposure, or for identification of important mediators of inflammation,
      proliferation and apoptosis. Progress in implementing a more effective strategy
      for in vitro-in vivo extrapolation and human risk assessment depends on
      significant advances in tissue culture technology and increasing their level of
      biological complexity. This article describes the current and ongoing need for
      more relevant, organotypic in vitro surrogate systems of human liver and recent
      efforts to recreate the multicellular architecture and hemodynamic properties of
      the liver using novel culture platforms. As these systems become more widely used
      for chemical and drug toxicity testing, there will be a corresponding need to
      establish standardized testing conditions, endpoint analyses and acceptance
      criteria. In the future, a balanced approach between sample throughput and
      biological relevance should provide better in vitro tools that are complementary
      with animal testing and assist in conducting more predictive human risk
      assessment.

PMID- 22583003
TI  - Anxious and angry rejection sensitivity, social withdrawal, and retribution in
      high and low ambiguous situations.
AB  - OBJECTIVE: Rejection sensitivity (RS) is a tendency to expect, perceive, and
      overreact to rejection. Our objective was to examine whether anxious and angry RS
      have specific associations with negative social reactions, and whether responses
      are intensified in situations of high rejection ambiguity. METHOD: In two
      studies, youth (N = 464 and N = 371) reported their RS and anticipated responses
      to social scenarios. In Study 1, all scenarios portrayed overt rejection events.
      In Study 2, participants were randomly assigned to conditions portraying overt or
      ambiguous rejection. RESULTS: Greater rejection expectation was associated with
      more negative reactions to rejection. Moreover, as expected, anxiety about
      rejection was uniquely associated with withdrawal, and anger about rejection was
      uniquely associated with retribution (i.e., reactive aggression). In the second
      study, RS persons responded more negatively than others to both overt and high
      ambiguous rejections, but retribution was intensified among participants high in
      rejection expectation when rejection was ambiguous, and withdrawal was
      intensified among participants high in anxious RS in overt rejection situations.
      CONCLUSIONS: Consistent with the revised RS model, there are different patterns
      of emotions, cognitions, and behaviors in response to high and low ambiguous
      rejection events, which are heightened in youth sensitive to rejection.

PMID- 22583004
TI  - Optimization of cold-adapted lysozyme production from the psychrophilic yeast
      Debaryomyces hansenii using statistical experimental methods.
AB  - Statistical experimental designs were employed to optimize culture conditions for
      cold-adapted lysozyme production of a psychrophilic yeast Debaryomyces hansenii.
      In the first step of optimization using Plackett-Burman design (PBD), peptone,
      glucose, temperature, and NaCl were identified as significant variables that
      affected lysozyme production, the formula was further optimized using a four
      factor central composite design (CCD) to understand their interaction and to
      determine their optimal levels. A quadratic model was developed and validated.
      Compared to the initial level (18.8 U/mL), the maximum lysozyme production (65.8
      U/mL) observed was approximately increased by 3.5-fold under the optimized
      conditions. PRACTICAL APPLICATION: Cold-adapted lysozymes production was first
      optimized using statistical experimental methods. A 3.5-fold enhancement of
      microbial lysozyme was gained after optimization. Such an improved production
      will facilitate the application of microbial lysozyme. Thus, D. hansenii lysozyme
      may be a good and new resource for the industrial production of cold-adapted
      lysozymes.

PMID- 22583005
TI  - Comparative analysis of the oocytes and early development of two species of
      curimatidae teleost fish.
AB  - Curimatella lepidura and Steindachnerina elegans are small forage fish,
      constituting an important link in the food chain, serving as food for larger
      commercial fish. In this study, characteristics of the eggs, of the oocyte's
      surface ultrastructure and of the embryogenesis are first described for these
      species. Absolute fecundity was 40864 +/- 8769 oocytes for C. lepidura and 22089
      +/- 8710 oocytes for S. elegans. Oocytes of both species are yellowish, weakly
      adhesive and with a post-fertilization diameter of 1019.5 +/- 20.6 MUm and 978.75
      +/- 29.16 MUm for C. lepidura and S. elegans, respectively. The ultrastructural
      analysis, using scanning electron microscopy, showed that the oocyte's surface of
      both species has pore canals over the entire surface and a funnel-shaped
      micropyle. At 24 degrees C, the embryonic development of C. lepidura was
      completed 25 h after fertilization, and blastopore closure occurred in 7 h 30
      min. In S. elegans, larvae hatched 20 h after fertilization, and blastopore
      closure occurred in 7 h 15 min. The fertilization rate was 74.5 +/- 7.96 and 71.2
      +/- 10.8% for C. lepidura and S. elegans, respectively. This study provides
      important support for clarifying phylogenetic relationships and in ecological and
      zoological understanding of Neotropical Curimatidae fish.

PMID- 22583006
TI  - Protective effect of polysaccharides on the stability of parenteral emulsions.
AB  - The main purpose of this study is to investigate the influence of two
      polysaccharides (dextran, hydroxyethyl starch) on the stability of parenteral
      emulsions. All parenteral emulsions were prepared by high-pressure
      homogenization. The influence of polysaccharides concentration was studied. The
      stabilities of autoclaving sterilization, centrifugation and freeze-thawing
      process were investigated extensively. Following the addition of polysaccharides,
      the stabilities of the parenteral emulsions were improved. A high-concentration
      polysaccharides solution (13%, w/v) produced better protection than a low one
      (1.3%, w/v), especially during freeze-thawing process. The protective mechanisms
      of polysaccharides were attributed to increasing systematic viscosity, non-frozen
      water absorbed by polysaccharides, formation of a linear bead-like structure and
      thicker mixed emulsifier film. Overall, polysaccharides can offer greatly
      increased protection for parenteral emulsions, and represent a novel protective
      strategy for improving the stability of this delivery system.

PMID- 22583007
TI  - Impact of age, weight and concomitant treatment on lamotrigine pharmacokinetics.
AB  - WHAT IS KNOWN AND OBJECTIVE: Lamotrigine metabolism may be substantially altered
      with concomitant administration of valproic acid and/or carbamazepine. Such
      alterations may require the adjustment of lamotrigine dose to ensure optimal
      treatment efficacy and safety. METHODS: The extent of lamotrigine interactions
      was investigated dependent on age, gender, weight and dose of concomitant
      carbamazepine and/or valproic acid in 65 patients with epilepsy. Lamotrigine
      plasma steady-state oral clearance (CLss/F) and area under the curve (AUCss) were
      calculated from the dose of drug, average steady-state concentration (Css) and
      interval of administration. Multiple regression analysis was used for the
      identification and quantification of factors that influenced lamotrigine
      pharmacokinetics. RESULTS AND DISCUSSION: Age and dose of carbamazepine and
      valproic acid had significant influence on lamotrigine CLss/F and AUCss.
      Carbamazepine was associated with a dose-dependent increase and valproic acid
      with a dose-dependent decrease of lamotrigine metabolism rate. The effect of
      carbamazepine was more pronounced. Younger patients were expected to metabolize
      lamotrigine more rapidly whereas overweight patients may be less susceptible to
      interactions. Gender had no influence on lamotrigine pharmacokinetics. WHAT IS
      NEW AND CONCLUSION: The efficacy and safety of lamotrigine may be altered by
      concomitant administration of carbamazepine and valproic acid. The models
      developed may be useful for estimating doses of lamotrigine for individual
      patients to minimize clinically significant interactions. Therapeutic monitoring
      is advisable when those drugs are used concomitantly.

PMID- 22583008
TI  - Fatty acid composition of the edible sea cucumber Athyonidium chilensis.
AB  - The edible sea cucumber Athyonidium chilensis is a fishery resource of high
      commercial value in Chile, but no information on its lipid and fatty acid
      composition has been previously reported. Phospholipids were the major lipid
      contents of the ethanolic extracts of tubules, internal organs and body wall of
      A. chilensis. Saturated fatty acids predominated in tubule phospholipids
      (40.69%), while in internal organs and body wall phospholipids, the
      monounsaturated fatty acids were in higher amounts (41.99% and 37.94%,
      respectively). The main polyunsaturated fatty acids in phospholipids were C20 :
      2omega-6, arachidonic (C20 : 4omega-6) and eicosapentaenoic (C20 : 5omega-3)
      acids. These results demonstrate for the first time that A. chilensis is a
      valuable food for human consumption in terms of fatty acids.

PMID- 22583009
TI  - Historical development of modern anesthesia.
AB  - Of all milestones and achievements in medicine, conquering pain must be one of
      the very few that has potentially affected every human being in the world. It was
      in 1846 that one of mankind's greatest fears, the pain of surgery, was
      eliminated. This historical review article describes how the various elements of
      anesthesiology (gasses, laryngoscopes, endotracheal tubes, intravenous
      medications, masks, and delivery systems) were discovered and how some brilliant
      entrepreneurs and physicians of the past two centuries have delivered them to
      humanity. One name stands out amongst all others when the founder of modern
      anesthesia is discussed, William T.G. Morton (1819-1868). A young Boston Dentist,
      Dr. Morton had been in the search for a better agent than what had been used by
      many dentists: nitrous oxide. With Dr. Morton's tenacity driven by enthusiasm and
      discovery, he and renowned surgeon at Massachusetts General Hospital, John
      Collins Warren (1778-1856) made history on October 16, 1846 with the first
      successful surgical procedure performed with anesthesia. Dr. Morton had single
      handedly proven to the world that ether is a gas that when inhaled in the proper
      dose, provided safe and effective anesthesia. One of the first accounts of an
      endotracheal tube being used for an airway comes from the pediatrician Joseph
      O'Dwyer (1841-1898). He used the metal "O'dwyer" tubes in diphtheria cases and
      passed them into the trachea blindly. Adding a cuff to the tube is credited to
      Arthur Guedel (1883-1956) and Ralph M. Waters (1883-1979) in 1932. This addition
      suddenly gave the practitioner the ability to provide positive pressure
      ventilation. The anesthesiologist Chevalier Jackson (1865-1958) promoted his
      handheld laryngoscope for the insertion of endotracheal tubes and its popularity
      quickly caught hold. Sir Robert Reynolds Macintosh's (1897-1989) breakthrough
      technique of direct laryngoscopy came after being appointed Nuffield professor of
      anesthetics at the University of Oxford in 1937. He was the first to describe the
      routinely placing of the tip of his newly re-designed laryngoscope in the
      epiglottic vallecula which is attached to the base of the tongue, thus when
      lifted exposed the entire larynx. Macintosh was genuinely astonished at what a
      great view he could achieve with his new blade and technique. The use of
      barbiturates as an intravenous anesthetic began in 1932. Sodium thiopental gained
      popularity after its use was described in detail by a Dr. John Lundy (1894-1973)
      of the Mayo Clinic. Other I.V. medications were tried over the past seventy
      years, but the newest induction drug which provided for a substantially shorter
      recovery period and seemed to actually suppress laryngeal reflexes has brought
      with it many benefits. Propofol, introduced clinically in 1977, demonstrated many
      positive effects even as an anti-emetic compound. Before October of 1846, surgery
      and pain were synonymous but not thereafter. As we entered the information age
      where the infrastructure of evidence based medicine and newer fields of genetics,
      transplantation, imaging radiology and even stem cells became quickly integrated
      into mainstream medicine, we can predict an excellent future on the progress to
      be made in anesthesia.

PMID- 22583010
TI  - Dabigatran versus warfarin after mechanical mitral valve replacement in the swine
      model.
AB  - BACKGROUND: Mechanical heart valve replacement is an absolute indication for
      anticoagulation. We report our experience comparing dabigatran to warfarin as
      thromboembolic prophylaxis after mechanical mitral valve replacement in the swine
      model. METHODS: Nineteen swine underwent mitral valve replacement with a
      regulatory approved, 27 mm mechanical valve. Two control groups consisted of
      three animals receiving no anticoagulation and five animals receiving warfarin (5
      mg once a day [QD], adjusted to maintain international normalized ratio [INR]
      from 2.0 to 2.5). The experimental group consisted of 11 animals receiving
      dabigatran (20 mg/kg twice a day [BID]). The study period was 90 days. The
      primary outcome was animal mortality; secondary outcomes included presence of
      thrombus and bleeding complications. RESULTS: The experimental group had four
      full-term survivors (40.0%); there were no full-term survivors in either control
      group. The average length of survival was 50.3 days in the experimental group
      compared with 18.7 and 15.6 days for the no anticoagulation and warfarin groups,
      respectively (p = .017). Valve thrombus was observed in all study groups.
      Hemorrhagic complications were present in 40% of the warfarin group and 27% of
      the dabigatran group. CONCLUSIONS: There was a significant mortality benefit to
      the use of dabigatran as thromboembolic prophylaxis when compared with warfarin
      in the setting of mechanical heart valve replacement in the swine model. There
      was also a decreased incidence of bleeding complications in the dabigatran group
      compared with the warfarin group. Valve thrombus was observed in all study
      groups. Any conclusions regarding the rate of thrombus formation are outside the
      scope of this study and merit further investigation.

PMID- 22583011
TI  - miR-17-5p as a novel prognostic marker for hepatocellular carcinoma.
AB  - OBJECTIVES: miRNAs are frequently deregulated in cancer and have shown promise as
      tissue-based markers for cancer classification and prognostication. Emerging
      evidence indicates that miR-17-5p plays an important role in carcinogenesis.
      However, the expression of miR-17-5p in HCC tissues and its clinical relevance
      has not been systematically studied yet, and whether miR-17-5p expression has
      influence on prognosis of HCC is still unknown. In this study, we investigate the
      expression and clinical significance of miR-17-5p in human HCC. METHODS: The
      expression levels of miR-17-5p were measured in 120 paired hepatocellular
      carcinoma (HCC) and paracarcinomatous liver tissues (PCLTs) derived from patients
      who underwent hepatic resection by qRT-PCR. Furthermore, the correlation of miR
      17-5p levels with clinicopathologic variables and prognosis was analyzed.
      RESULTS: miR-17-5p was significantly upregulated in HCCs (p < .001). Furthermore,
      HCC with metastasis had higher miR-17-5p levels than that without metastasis (p <
      .001). Importantly, the elevated expression of miR-17-5p correlated with multiple
      tumor nodules (p = .046), worse Edmondson-Steiner grade (p = .024), vein invasion
      (p = .001), shortened overall survival (p = .012), and disease-free survival (p =
      .011) of HCC. Multivariable Cox regression analysis revealed that miR-17-5p was
      an independent risk factor for overall survival and disease-free survival (p =
      .002 and p = .042, respectively). CONCLUSION: miR-17-5p is highly elevated in
      HCC, especially in HCC with metastasis. miR-17-5p can serve as a novel prognostic
      marker for HCC.

PMID- 22583013
TI  - The effect of visceral fat mass on pancreatic fistula after
      pancreaticoduodenectomy.
AB  - BACKGROUND: Obesity is associated with perioperative complications and has been
      considered a risk factor for surgical outcomes of patients undergoing abdominal
      surgery. The aim of this study is to evaluate the impact of the amount of
      visceral fat on postoperative morbidity of patients who underwent
      pancreaticoduodenectomy (PD). METHODS: We reviewed 181 patients who underwent
      surgery for periampullary lesions at the Department of Surgery, Gangnam Severance
      Hospital, Yonsei University Health System between January 2003 and June 2010. The
      visceral fat area (VFA) and subcutaneous fat area were calculated by computed
      tomography software. RESULTS: The mean body mass index (BMI) was 23.4 kg/m(2) (+/
      3.1 kg/m(2)), and the mean VFA was 94.4 cm(2) (+/-49.5 cm(2)). The mean
      intraoperative blood loss, and the incidence of clinically relevant pancreatic
      fistula (grade B/C) and clinically relevant delayed gastric emptying (grade B/C)
      were significantly higher in the high-VFA group (>=100 cm(2)). In univariate
      analysis, the incidence of clinically relevant pancreatic fistula (grade B/C) was
      significantly higher in the high-BMI group (>=25 kg/m(2)), the high-VFA
      group(>=100 cm(2)), the large intraoperative blood loss and transfusion group,
      and in patients with pathology of nonpancreatic origin (ampulla, bile duct, or
      duodenum). In multivariate analysis, the high-VFA group (>=100 cm(2)) and
      patients with pathology of nonpancreatic origin were identified as independent
      factors for clinically relevant pancreatic fistula. CONCLUSION: VFA is a better
      indicator for the development of pancreatic fistula after PD than BMI. High VFA
      (>=100 cm(2)) is a risk factor for developing a pancreatic fistula after PD.

PMID- 22583012
TI  - Ischemia-reperfusion-induced unmeasured anion generation and glycocalyx shedding:
      sevoflurane versus propofol anesthesia.
AB  - INTRODUCTION: Vascular leakage after ischemia-reperfusion (IR) is largely
      attributed to the destruction of the endothelial barrier and its associated
      negatively charged glycocalyx. In vitro, sevoflurane attenuates these changes.
      Therefore, we compared sevoflurane with propofol with regard to the protection of
      the glycocalyx and the release of negatively charged substances in vivo. METHODS:
      After surgical preparation under midazolam-fentanyl, nine pigs each received
      either propofol or sevoflurane. Ischemia of 90 min was induced by a balloon
      catheter in the thoracic aorta. After 120 min of reperfusion, the anesthetics
      were changed back to midazolam-fentanyl. Five animals, each without aortic
      occlusion, served as time controls. Blood electrolyte parameters were measured,
      from which the strong ion gap (SIG) was calculated. Serum heparan sulfate
      concentrations and immunohistology served as a marker of glycocalyx destruction.
      RESULTS: Immediately after reperfusion, SIG increased significantly only in the
      propofol group (+6.7 mEq/l versus baseline; p < .05), remaining stable in
      sevoflurane and both time-controlled groups. Initially, heparan sulfate
      concentration increased comparably in both experimental groups, but after 120
      min, it became stable in sevoflurane-anesthetized animals, while increasing
      further in the propofol group (p < .05). CONCLUSIONS: Unmeasured anions,
      predictive of negative outcome in previous studies, did not increase
      significantly in sevoflurane-anesthetized animals. Additionally, there was less
      heparan sulfate shedding over time, signaling less destruction of the glycocalyx.
      Therefore, in this in-vivo situation, sevoflurane proves to be superior to
      propofol in protecting the endothelium from IR injury.

PMID- 22583014
TI  - Remote efficacy for two different forms of hyaluronate-based adhesion barriers.
AB  - BACKGROUND: Chemically modified sodium hyaluronate and carboxymethylcellulose
      (HA/CMC) membrane clinically reduces adhesion formation following surgery but was
      not designed for laparoscopic use. HA/CMC powder of identical chemical
      composition has been developed to allow for application laparoscopically. We
      compared the adhesion reduction efficacy of HA/CMC powder and film when applied
      directly to or remote from sites of surgical trauma. We also investigated the
      effect of the powder on wound healing. MATERIALS AND METHODS: Two animal models
      of adhesion formation were used to evaluate efficacy: a rat peritoneal sidewall
      defect model and a rabbit cecal abrasion/sidewall defect model. The products were
      applied directly to the defect or the contralateral sidewall. Adhesions were
      examined seven days after surgery. In a separate study, the effect of the powder
      on healing was evaluated at 5, 7, and 28 days using a rat incisional wound
      strength model. RESULTS: HA/CMC powder and film, when applied directly to the
      peritoneal defect, significantly reduced adhesions relative to the untreated
      control in both models. Remote applications of HA/CMC powder also reduced
      adhesions. In contrast, remote applications of HA/CMC film had no effect. HA/CMC
      powder did not significantly alter incisional wound strength at any of the
      timepoints tested. CONCLUSION: In our preclinical models, HA/CMC powder had
      similar adhesion reduction efficacy to HA/CMC film when applied directly to sites
      of trauma. In addition, HA/CMC powder reduced adhesions remote from the
      application site. Importantly, HA/CMC powder did not impair incisional wound
      healing. On the basis of these results, future investigation of HA/CMC powder is
      warranted.

PMID- 22583016
TI  - Implantation and monitoring of a novel telemetry unit in the Syrian golden
      hamster model.
AB  - Radiotelemetry allows for real-time remote monitoring of biological parameters in
      freely moving laboratory animals. The HD-X11 transmitter is a novel telemetry
      device that enables simultaneous collection of body temperature, activity, blood
      pressure, electrocardiogram (ECG), and other biopotentials in small animal
      models. Previously, researchers could only collect either blood pressure or ECG
      parameters; prioritizing the signal of most interest or increasing the number of
      animals on study to capture both signals at one time. This new device eliminates
      the need for separate animal groups for assorted measurements and allows for a
      more complete cardiovascular assessment. Evaluation of the transmitter from both
      surgical and data collection perspectives indicates that the HD-X11 transmitter
      can be a useful tool to researchers in a wide range of scientific and medical
      fields.

PMID- 22583015
TI  - Outcomes of Wilms' tumor in eastern China: 10 years of experience at a single
      center.
AB  - PURPOSE: Wilms' tumor (WT), or nephroblastoma, is the most common renal
      malignancy of childhood, and its outcome varies. We aimed to retrospectively
      review the clinical parameters and outcomes of WT cases treated at our medical
      center to identify factors associated with its prognosis. METHODS: We
      retrospectively reviewed WT patients who had undergone surgery and other therapy
      in our hospital from May 1998 to May 2008. Demographic features, mode of
      presentation, stage of tumor, histopathologic results, and survival rates were
      evaluated. RESULTS: Our study included 67 children with WT; 38 were males and 29
      were females. The mean age at onset was 39 months. Eighteen cases were diagnosed
      as Stage I, 23 as Stage II, 20 as Stage III, and 6 as Stage IV.
      Nephroureterectomy was the initial treatment in 57 children. There were 46
      (68.7%) cases of favorable histology and 21 (31.3%) cases of unfavorable
      (anaplastic) histology. The rates of four-year event-free survival and overall
      survival were 78.3% and 81%, respectively. The four-year overall survival rate
      for cases of favorable histology (85.8%) was higher than for those with
      unfavorable histology (71.4%; p =.028). CONCLUSIONS: The outcomes of WT patients
      in our institution were little poorer than for those of the third National Wilms
      Tumor Study. Advanced clinical stage at presentation, unfavorable histology,
      tumor rupture, relapse, delay of radiotherapy due to ignorance, and premature
      ending of treatment were the important factors that impacted on the outcome of
      WT.

PMID- 22583017
TI  - Assisted ventilation without endotracheal intubation in rats.
AB  - This technique was performed to allow for an additional approach to assist in
      ventilation. A modified ventilation nose cone was placed over the nose, which
      allowed the animal to not require endotracheal intubation. This method was
      effective in ventilating the animals during thoracic and abdominal procedures
      without requiring endotracheal intubation.

PMID- 22583019
TI  - Substrates for efficient fluorometric screening employing the NAD-dependent
      sirtuin 5 lysine deacylase (KDAC) enzyme.
AB  - The class III lysine deacylases (KDACs), also known as the sirtuins, have emerged
      as interesting drug targets for therapeutic intervention in a variety of
      diseases. To gain a deeper understanding of the processes affected by sirtuins,
      the development of selective small molecule modulators of individual isozymes has
      been a longstanding goal. Essential for the discovery of novel modulators,
      however, are good screening protocols and mechanistic insights with regard to the
      targets in question. We therefore evaluated the activities of the seven human
      sirtuin hydrolases against a panel of fluorogenic substrates. Both commonly used,
      commercially available substrates and novel chemotypes designed to address recent
      developments in the field of lysine post-translational modification were
      evaluated. Our investigations led to the discovery of two new fluorogenic epsilon
      N-succinyllysine-containing substrates that enable highly efficient and enzyme
      economical screening employing sirtuin 5 (SIRT5). Furthermore, optimized
      protocols for facile kinetic investigations were developed, which should be
      valuable for enzyme kinetic investigations. Finally, these protocols were applied
      to a kinetic analysis of the inhibition of SIRT5 by suramin, a potent sirtuin
      inhibitor previously shown by X-ray crystallography to bind the substrate pocket
      of the human SIRT5 KDAC enzyme.

PMID- 22583021
TI  - Interaction of barley beta-glucan and tea polyphenols on glucose metabolism in
      streptozotocin-induced diabetic rats.
AB  - Soluble dietary fiber and antioxidants have received much attention as most
      important components of functional foods. However, few data are available on the
      effects of the combination of tea polyphenols (TP) and beta-glucan (BG) on blood
      glucose in a diabetic rat. The effects of administration of barley BG and TP or
      their combination (TP + BG) on blood glucose, lipid profiles, and antioxidant
      parameters on streptozotocin-induced diabetic rats were investigated. Significant
      improvements on the blood glucose level, serum lipid parameters (decreases in
      triglyceride, total cholesterol, LDL-C, and increase in HDL-C), lipid
      peroxidation (decrease in malondiadehyde content), and serum antioxidant status
      (increases in superoxide dismutase, glutathione peroxidase, and total antioxidant
      capacity) resulted in diabetic rats after administering TP + BG. This study,
      therefore, demonstrated that the intake of TP + BG has beneficial effects on
      glucose tolerance, lipid metabolism, and serum antioxidant status. It also
      revealed that TP + BG is better than TP or BG alone in improving glucose
      metabolism and antioxidant status in diabetic rats. Practically, the present
      study suggested that polyphenols-rich cereal foods are help for type 2 diabetes.
      PRACTICAL APPLICATION: Although TP or BG was definitely helpful in the treatment
      and management of diabetes mellitus, synthetic anti-hyperglycemic effects were
      found between TP and BG. The fortification of a BG-rich cereal diet with TP could
      be used as a strategy to maintain health of diabetic subjects.

PMID- 22583023
TI  - Winter survival and deacclimation of perennials under warming climate:
      physiological perspectives.
AB  - Appropriate timing and rate of cold deacclimation and the ability to reacclimate
      are important components of winter survival of perennials in temperate and boreal
      zones. In association with the progressive increase in atmospheric CO2, temperate
      and boreal winters are becoming progressively milder, and temperature patterns
      are becoming irregular with increasing risk of unseasonable warm spells during
      the colder periods of plants' annual cycle. Because deacclimation is mainly
      driven by temperature, these changes pose a risk for untimely/premature
      deacclimation, thereby rendering plant tissue vulnerable to freeze-injury by a
      subsequent frost. Research also indicates that elevated CO2 may directly impact
      deacclimation. Hence, understanding the underlying cellular mechanisms of how
      deacclimation and reacclimation capacity are affected by changes in environmental
      conditions is important to ensure winter survival and the sustainability of plant
      sources under changing climate. Relative to cold acclimation, deacclimation is a
      little studied process, but the limited evidence points to specific changes
      occurring in the transcriptome and proteome during deacclimation. Loss of
      freezing tolerance is additionally associated with substantial changes in
      cell/tissue-water relations and carbohydrate metabolism; the latter also impacted
      by temperature-driven, altered respiratory metabolism. This review summarizes
      recent progress in understanding the physiological mechanisms of deacclimation
      and how they may be impacted by climate change.

PMID- 22583022
TI  - Genetic and functional analysis of HIV type 1 nef gene derived from long-term
      nonprogressor children: association of attenuated variants with slow progression
      to pediatric AIDS.
AB  - Among persons infected by HIV-1, the rate of progression to AIDS is
      multifactorial being affected by host and viral factors, including the HIV
      encoded negative factor (Nef). Our aim was to define whether variations in the
      nef gene as well as its functions may be associated with slower HIV disease
      course in infected children. The proviral HIV-1 nef gene was cloned, sequenced,
      and compared in children with contrasting disease course: 10 long-term
      nonprogressors (LTNP) and six rapid progressor (RP). The CD4 and MHC-I down
      modulation ability of nef alleles derived from LTNP and RP children was analyzed.
      We observed that only one of our 10 LTNP had a protective genetic background, and
      out of them, 40% had defective nef genes, carrying substitutions at the
      (AWLEAQ(56-61)) and the (Rxx(22-24)) domains, and that those alleles were unable
      of down-regulate CD4 and MHC-I. The emergence or presence of Nef L58V
      substitution was associated with viral attenuation, indicated by a reduction in
      HIV viral loads, a persistent preservation of CD4(+) T cell counts, and lack of
      AIDS-related symptoms. Our results demonstrate that HIV-1 perinatally infected
      children carrying functionally defective nef HIV-1 strains have prolonged
      asymptomatic phases without therapy, suggesting a relevant role of CD4 and MHC-I
      down-modulation Nef domains on in vivo HIV-1 pathogenesis and pediatric
      immunodeficiency outcome.

PMID- 22583024
TI  - TOPPAS: a graphical workflow editor for the analysis of high-throughput
      proteomics data.
AB  - Mass spectrometry coupled to high-performance liquid chromatography (HPLC-MS) is
      evolving more quickly than ever. A wide range of different instrument types and
      experimental setups are commonly used. Modern instruments acquire huge amounts of
      data, thus requiring tools for an efficient and automated data analysis. Most
      existing software for analyzing HPLC-MS data is monolithic and tailored toward a
      specific application. A more flexible alternative consists of pipeline-based tool
      kits allowing the construction of custom analysis workflows from small building
      blocks, e.g., the Trans Proteomics Pipeline (TPP) or The OpenMS Proteomics
      Pipeline (TOPP). One drawback, however, is the hurdle of setting up complex
      workflows using command line tools. We present TOPPAS, The OpenMS Proteomics
      Pipeline ASsistant, a graphical user interface (GUI) for rapid composition of
      HPLC-MS analysis workflows. Workflow construction reduces to simple drag-and-drop
      of analysis tools and adding connections in between. Integration of external
      tools into these workflows is possible as well. Once workflows have been
      developed, they can be deployed in other workflow management systems or batch
      processing systems in a fully automated fashion. The implementation is portable
      and has been tested under Windows, Mac OS X, and Linux. TOPPAS is open-source
      software and available free of charge at http://www.OpenMS.de/TOPPAS .

PMID- 22583025
TI  - Nutritional lipid supply can control the heat shock response of B16 melanoma
      cells in culture.
AB  - The in vitro culture of cells offers an extremely valuable method for probing
      biochemical questions and many commonly-used protocols are available. For
      mammalian cells a source of lipid is usually provided in the serum component. In
      this study we examined the question as to whether the nature of the lipid could
      become limiting at high cell densities and, therefore, prospectively influence
      the metabolism and physiology of the cells themselves. When B16 mouse melanoma
      cells were cultured, we noted a marked decrease in the proportions of n-3 and n-6
      polyunsaturated fatty acids (PUFAs) with increasing cell density. This was
      despite considerable quantities of these PUFAs still remaining in the culture
      medium and seemed to reflect the preferential uptake of unesterified PUFA rather
      than other lipid classes from the media. The reduction in B16 total PUFA was
      reflected in changes in about 70% of the molecular species of membrane
      phosphoglycerides which were analysed by mass spectrometry. The importance of
      this finding lies in the need for n-3 and n-6 PUFA in mammalian cells (which
      cannot synthesize their own). Although the cholesterol content of cells was
      unchanged the amount of cholesterol enrichment in membrane rafts (as assessed by
      fluorescence) was severely decreased, simultaneous with a reduced heat shock
      response following exposure to 42 degrees C. These data emphasize the pivotal
      role of nutrient supply (in this case for PUFAs) in modifying responses to stress
      and highlight the need for the careful control of culture conditions when
      assessing cellular responses in vitro.

PMID- 22583026
TI  - Translating evidence-based practices into policy: a case study in Texas.
AB  - Screening and brief intervention (SBI) in health care settings is an evidence
      based practice for substance misuse. The Uniform Accident and Sickness Policy
      Provision Law (UPPL) discourages providers from carrying out SBI by allowing
      insurers in 26 states to refuse coverage for injuries resulting from
      intoxication. This project used a qualitative case study methodology to
      understand how policy-advocacy communication may have impacted the success of
      UPPL repeal efforts in Texas. Results showed bill progress could have been
      impeded due to less-effective communication from advocates. These findings
      suggest the quality of communication may influence the success of evidence-based
      policy-advocacy for UPPL repeal.

PMID- 22583027
TI  - Mothers whose children have ADD/ADHD discuss their children's medication use: an
      investigation of blogs.
AB  - This article presents the results of a frame and discourse analysis of Internet
      blog sites where parents (usually mothers) discuss their concerns about
      medication use by their children with attention deficit disorder or attention
      deficit hyperactivity disorder (ADD/ADHD). This is a particularly important topic
      in an era characterized by powerful circulating discourses around the contentious
      medicalization of, and prevalent pharmaceutical treatments for, ADD/ADHD, as well
      as the mother blame associated with having a child diagnosed with ADD/ADHD. The
      findings document that the mothers see ADD/ADHD as legitimate medical diagnoses
      and view themselves as caretakers of children with brain and neuro-chemical
      anomalies affecting the behavior of their children. They favor pharmaceutical use
      and describe themselves as experts in the difficult and complex issues related to
      pharmaceuticalized parenting. At the same time their adoption of medicalization
      is contingent as they express specific critiques of some doctors, some types of
      doctors, and critically evaluate science.

PMID- 22583028
TI  - Preparing families of children with special health care needs for disasters: an
      education intervention.
AB  - Children with special health care needs pose a special challenge in post-disaster
      response. Current research suggests that the general population is not adequately
      prepared for a major disaster event, with members of vulnerable populations even
      less prepared. The purpose of this study was to determine the short-term
      effectiveness of a brief patient education intervention aimed at increasing
      levels of disaster preparedness among families of special health care needs
      children. One hundred twenty-one families were randomly assigned to either
      intervention or intervention plus incentive group. Families were surveyed prior
      to the intervention using a previously published instrument on family
      preparedness, and at 30-45 days post-intervention. A Preparedness Score was
      assigned to each family based on the number of items completed on the
      preparedness instrument. Significant differences were found between pre- and
      posttest scores for families that received the intervention, regardless of
      whether or not an incentive item was provided. Posttest scores were significantly
      higher than pretest scores, suggesting that the intervention was successful in
      increasing short-term overall levels of family preparedness in this population.

PMID- 22583029
TI  - Effectiveness of community health workers in providing outreach and education for
      colorectal cancer screening in Appalachian Kentucky.
AB  - The purpose of this study was to examine the effectiveness of a community health
      worker (CHW)-delivered cancer education program designed to increase knowledge
      and awareness of colorectal cancer screening options. The study population was an
      extremely vulnerable and medically underserved geographic region in Appalachian
      Kentucky. CHWs enrolled participants in face-to-face visits, obtained informed
      consent, and administered a baseline assessment of knowledge of colorectal cancer
      risks and the benefits of screening and screening history. An educational
      intervention was then provided and participants were re-contacted 6 months later
      when a posttest was administered. The mean score of the 637 participants
      increased from 4.27 at baseline to 4.57 at follow-up (p < .001). Participants who
      reported asking their health care provider about colorectal cancer screening
      increased from 27.6% at baseline to 34.1% at follow-up (p = .013). Results
      suggest that CHWs were very effective at maintaining the study population; no
      loss to follow-up occurred. The results also showed increased knowledge and
      awareness about colorectal cancer screening education. Implications for social
      work practice, policy and research are discussed.

PMID- 22583030
TI  - Assessing an interdisciplinary health care model: the Governor's Wellmobile
      Program.
AB  - This article assesses the applicability of Bronstein's (2003) generic model of
      interdisciplinary collaboration in the context of a newly created collaboration
      providing community-based health care services, the Governor's Wellmobile
      Program. An analysis of the program's quarterly reports and interviews with
      faculty and students involved in the collaboration offers an assessment of the
      model and implications for interdisciplinary social work practice in community
      health care delivery.

PMID- 22583031
TI  - HIV positive Hispanic/Latinos who delay HIV care: analysis of multilevel care
      engagement barriers.
AB  - This article overviews a Health Resources and Services Administration (HRSA)
      study with a sample population consisting of 470 Hispanic/Latino persons living
      with HIV/AIDS who received primary HIV/AIDS medical services from one of five
      HRSA Special Projects of National Significance (SPNS) Border Health demonstration
      projects. The study purpose was to identify multilevel barriers that affect
      delayed entry into HIV/AIDS medical care among Hispanic/Latino persons living
      along the U.S.-Mexico border. Multilevel variables along individual,
      community/cultural, and structural/systems were assessed relative to delayed care
      entry. The results of this examination indicate that individual and
      structural/system-level variables affect delayed care entry, whereas support was
      not found for community/cultural-level barriers. Study findings inform treatment
      engagement strategies aimed to decrease HIV disease progression by bringing
      Hispanic/Latinos into care sooner.

PMID- 22583033
TI  - Public services for children with special needs: discrimination by diagnosis.

PMID- 22583034
TI  - Differential modulations of ipsilateral and contralateral beta
      (de)synchronization during unimanual force production.
AB  - Unilateral movement is usually accompanied by ipsilateral activity in the primary
      motor cortex (M1). It is still largely unclear whether this activity reflects
      interhemispheric 'cross-talk' of contralateral M1 that facilitates movement, or
      results from processes that inhibit motor output. We investigated the role of
      beta power in ipsilateral M1 during unimanual force production. Significant
      ipsilateral beta desynchronization occurred during continuous dynamic but not
      during static force production. Moreover, event-related time-frequency analysis
      revealed bilateral desynchronization patterns, whereas post-movement
      synchronization was confined to the contralateral hemisphere. Our findings
      indicate that ipsilateral activation is not merely the result of interhemispheric
      cross-talk but involves additional processes. Given observations of differential
      blood oxygen level-dependent responses in ipsilateral and contralateral M1, and
      the correlation between beta desynchronization and the firing rate of pyramidal
      tract neurons in contralateral M1 during movement, we speculate that beta
      desynchronization in contra- and ipsilateral M1 arises from distinct neural
      activation patterns.

PMID- 22583035
TI  - On-target labeling of intracellular metabolites combined with chemical mapping of
      individual hyphae revealing cytoplasmic relocation of isotopologues.
AB  - A microscale analytical platform integrating microbial cell culture, isotopic
      labeling, along with visual and mass spectrometric imaging with single-cell
      resolution has been developed and applied in the monitoring of cellular
      metabolism in fungal mycelium. The method implements open chips with a two
      dimensional surface pattern composed of hydrophobic and hydrophilic zones. Two
      hydrophilic islands are used as medium reservoirs, while the hydrophobic area
      constitutes the support for the growing aerial hyphae, which do not have direct
      contact with the medium. The first island, containing (12)C(6)-glucose medium,
      was initially inoculated with the mycelium (Neurospora crassa), and following the
      initial incubation period, the hyphae progressed toward the second medium island,
      containing an isotopically labeled substrate ((13)C(6)-glucose). The (13)C atoms
      were gradually incorporated into cellular metabolites, which was revealed by
      MALDI-MS. The fate of the chitin-biosynthesis precursor, uridine diphosphate N
      acetylglucosamine (UDP-GlcNAc), was monitored by recording mass spectra with
      characteristic isotopic patterns, which indicated the presence of various
      (12)C/(13)C isotopologues. The method enabled mapping the (13)C-labeled UDP
      GlcNAc in fungal mycelium and recording its redistribution in hyphae, directly on
      the chip.

PMID- 22583036
TI  - From the cradle to the grave: age differences in attachment from early adulthood
      to old age.
AB  - OBJECTIVE: Although attachment dynamics are thought to be important across the
      life span, relatively few studies have examined attachment processes beyond young
      adulthood. Extant research on age differences in attachment orientation has
      yielded conflicting results and interpretations. The purpose of this study was to
      provide a more complete picture of age-related differences in attachment anxiety
      and avoidance. METHOD: We examined attachment anxiety and avoidance in 86,555
      Internet respondents (71.8% female) ranging in age from 18 to 70. RESULTS: We
      found that attachment anxiety was highest among younger adults and lowest among
      middle-aged and older adults. Attachment avoidance showed less dramatic age
      differences overall but was highest among middle-aged adults and lowest among
      younger and older adults. In addition, partnered individuals reported lower
      levels of attachment anxiety and avoidance compared to single individuals,
      particularly in younger and older adulthood. Women also reported slightly higher
      anxiety and avoidance compared to men, especially in young adulthood.
      CONCLUSIONS: Findings are discussed in the context of life span changes in social
      roles, normative personality development, and emotion regulation throughout
      adulthood.

PMID- 22583037
TI  - Re: Transventricular edge-to-edge repair of the mitral valve during surgical
      ventricular restoration: review of the literature.

PMID- 22583038
TI  - Thrombopoietin receptor agonists in refractory immune thrombocytopenia:
      differential responses to eltrombopag and romiplostim: a case report and possible
      explanations.
AB  - WHAT IS KNOWN AND OBJECTIVE: Although new thrombopoietin (TPO) receptor agonist
      drugs, such as romiplostim and eltrombopag, are highly effective and well
      tolerated for patients with immune thrombocytopenia (ITP) refractory to first
      line treatments such as prednisolone, the cross-resistance of these two TPO
      receptor agonists is still unknown. CASE SUMMARY: An 84-year-old Japanese female
      patient with steroid-refractory ITP received eltrombopag with a gradually
      increasing dose schedule from 12.5 to 25 mg/day, 37.5 mg/day and finally 50
      mg/day. As no increase in platelet count was observed even at the maximum dose of
      50 mg/day, and eltrombopag-related grade 3 elevation of aspartate
      aminotransferase was observed, another TPO receptor agonist, romiplostim, was
      administered at 1 MUg/kg/week subcutaneously. A rapid increase in platelet count
      was observed 1 week after the first injection. The dose of romiplostim was
      escalated to 4 MUg/kg according to the platelet count and a complete response was
      achieved 7 weeks after the first injection without any adverse events. WHAT IS
      NEW AND CONCLUSION: The successful treatment of ITP refractory to eltrombopag
      with romiplostim strongly suggests that the absence of cross-resistance between
      these two approved TPO receptor agonists and possible differences in mechanism of
      action. Further study of the mechanisms of action of TPO receptor agonists is
      called for along with further exploration of the potential of romiplostim in
      refractory ITP.

PMID- 22583040
TI  - Self-determination: a buffer against suicide ideation.
AB  - Self-determination was examined as a protective factor against the detrimental
      impact of negative life events on suicide ideation in adolescents. It is
      postulated that for highly self-determined adolescents, negative life events have
      a weaker impact on both hopelessness and suicide ideation than for non-self
      determined adolescents. In turn, hopelessness is hypothesized to generate less
      suicide ideation for highly self-determined individuals. Results from multigroup
      analyses confirm that both the direct and indirect links between negative life
      events and suicide ideation were significantly weaker among participants high in
      self-determination. The protective role of self-determination against negative
      life events is discussed.

PMID- 22583039
TI  - Formal [4 + 1]- and [5 + 1]-annulation by an S(N)2-conjugate addition sequence:
      stereoselective synthesis of highly substituted carbocycles.
AB  - K(2)CO(3)-mediated reactions of 6-bromo-2-hexenoates and 7-bromo-2-heptenoate
      with active methylene compounds deliver highly substituted cyclopentane and
      cyclohexane derivatives, respectively via a sequence of S(N)2-conjugate addition
      reactions (formal [4 + 1]- and [5 + 1]-annulation) in a diastereoselective
      manner.

PMID- 22583041
TI  - Analytical traceability of melon (Cucumis melo var reticulatus): proximate
      composition, bioactive compounds, and antioxidant capacity in relation to
      cultivar, plant physiology state, and seasonal variability.
AB  - Two morphologically different cultivars of Italian melons (Baggio and Giusto)
      were characterized considering samples harvested in different times, at the
      beginning (BPP) and at the end of the physiological plant production period
      (EPP). Proximate composition, protein, minerals, pH, phenolic content,
      antioxidant capacity, ascorbic acid, carotenoids, condensed tannins, and
      flavonoids were measured, showing a significant decrease in EPP samples
      (phenolics, antioxidant capacity, condensed tannins, and flavonoids); ascorbic
      acid decreased in Giusto cv, carotenoids in Baggio cv. Mineral content increased
      in either the cultivars (EPP samples). Year-to-year difference was significantly
      highlighted; the plant growing cycle significantly affected the chemotype.
      Despite these effects, the Principal Component Analysis (PCA) permitted the
      discrimination of Baggio from Giusto cv, and the discrimination of BPP from EPP
      samples as well.

PMID- 22583042
TI  - The prevalence of endometrial hyperplasia and endometrial cancer in women with
      polycystic ovary syndrome or hyperandrogenism.
AB  - OBJECTIVE: Polycystic ovary syndrome may be associated with an increased risk of
      endometrial hyperplasia and endometrial cancer, but substantial evidence for this
      remains to be established. We investigated the prevalence of endometrial
      hyperplasia and endometrial cancer in a well characterized group of women with
      polycystic ovary syndrome and/or clinical/biochemical hyperandrogenism. DESIGN:
      Retrospective observational trans-sectional study. SETTING: Out-patient clinic at
      the Departments of Endocrinology and Gynecology, Odense University Hospital,
      Denmark. POPULATION: In all, 963 premenopausal women consecutively referred with
      the diagnoses polycystic ovary syndrome and/or hirsutism during 1997-2008.
      METHODS: All women underwent a standardized evaluation program. In 2011, The
      Danish Data Bank of Pathology was used to identify women with endometrial
      histology diagnoses (year range of diagnosis 1982-2011). Main outcome measures.
      Histology diagnoses, demographic variables. RESULTS: Endometrial hyperplasia was
      diagnosed in 10 (1.0%) women and endometrial cancer in one (0.1%) woman. The
      median body mass index of these women was 30.6 kg/m(2) compared with 26.8 kg/m(2)
      in the total cohort. There were no differences between the cases and total cohort
      in terms of individual Rotterdam Criteria. In Denmark, 70 cases of endometrial
      cancer are diagnosed yearly in women 40-55 years, a prevalence of 0.4% in the
      corresponding period. CONCLUSION: The results of the present study do not suggest
      a higher prevalence of endometrial cancer in women with polycystic ovary syndrome
      and/or clinical/biochemical hyperandrogenism than in the general population.

PMID- 22583043
TI  - 7-Ethyl-10-hydroxycamptothecin proliposomes with a novel preparation method:
      optimized formulation, characterization and in-vivo evaluation.
AB  - CONTEXT: The proliposomes were used to solve the stability of the ordinary
      liposomes. OBJECTIVE: 7-ethyl-10-hydroxycamptothecin (SN-38) proliposomes for
      intravenous (i.v.) administration were prepared successfully by a new method.
      MATERIALS AND METHODS: SN-38 liposomes solution was reconstituting automatically
      from proliposomes on contact with the acetic acid buffer solution (0.2 M, pH
      2.6). The formulation was optimized by the Box-Behnken design. The
      physicochemical characteristics of the SN-38 proliposomes were studied by
      scanning electron microscopy (SEM), transmission electron microscopy (TEM),
      differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The
      stability studies were also carried on. The FLU-HPLC system was served to study
      the concentration of SN-38 in the plasma of Sprague Dawley (SD) rats. RESULTS:
      The optimized formulation was SN-38: 0.03 g; Soybean phospholipid (SP): 0.6 g;
      dextrose: 3.00 g. The entrapment efficiency of the optimized formulation was >85%
      and the mean particle size was about 231 nm. The stability studies showed that SN
      38 proliposomes were stable in dark at 20-25 degrees C for 6 months at least. The
      pharmacokinetic parameters of i.v. administration demonstrated that the half-life
      of SN-38 loaded in the liposomes was prolonged in vivo. DISCUSSION AND
      CONCLUSION: The SN-38 proliposomes was prepared successful by the analysis of
      TEM, SEM, DSC and XRD, and SN-38 liposomes could be reconstituted on contact with
      the hydration medium. SN-38 liposomes circulated for a longer time in the blood
      circulating system than SN-38 solution, which contributed to maintaining the drug
      action.

PMID- 22583044
TI  - Chemical composition of the essential oils of Annona pickelii and Annona
      salzmannii (Annonaceae), and their antitumour and trypanocidal activities.
AB  - The essential oils from the leaves of Annona pickelii and Annona salzmannii
      (Annonaceae) were obtained by hydrodistillation using a Clevenger apparatus, and
      analysed by GC-MS and GC-FID. A total of 21 compounds were identified in the
      essential oil of A. pickelii and 23 in that of A. salzmannii; sesquiterpenes
      predominated in both essential oils. Bicyclogermacrene (38.0%), (E)-caryophyllene
      (27.8%), alpha-copaene (6.9%) and alpha-humulene (4.0%) were the main components
      of A. pickelii, while delta-cadinene (22.6%), (E)-caryophyllene (21.4%), alpha
      copaene (13.3%), bicyclogermacrene (11.3%) and germacrene D (6.9%) were the main
      components of A. salzmannii. The biological activities of the essential oils
      against Trypanosoma cruzi epimastigote forms and cytotoxicity against tumour cell
      lines (antitumour) were investigated. The essential oils showed potent
      trypanocidal and antitumour activities with values of IC50 lower than 100 ug mL(
      1).

PMID- 22583045
TI  - Simple ligand-field theory of d4 and d6 transition metal complexes with a C3
      symmetry axis.
AB  - There have been a number of recent studies reporting high-spin d(4,6) complexes
      with three- and four-coordinate geometry, which exhibit roughly trigonal
      symmetry. These include complexes of Fe(II) with general formula L(3)FeX, where L
      = thioether or dialkylphosphine donors of a tripodal chelating ligand and X is a
      monodentate ligand on the C(3) axis. In these systems, there is unquenched
      orbital angular momentum, which has significant consequences on the
      electronic/magnetic properties of the complexes, including magnetic
      susceptibility, EPR spectra, and magnetic Mossbauer spectra. We describe here a
      simple model using a description of the d orbitals with trigonal symmetry that
      along with the application of the spin-orbit interaction successfully explains
      the magnetic properties of such systems. These d orbitals with 3-fold symmetry
      are complex orbitals with a parameter, a, that is determined by the bond angle,
      alpha, of LFeX. We demonstrate that the E symmetry states in such systems with S
      > 1/2 cannot be properly "simulated by" or be "represented by" the Zeeman and
      second-order zero-field spin Hamiltonian alone because by definition the
      parameters D and E are second-order terms. One must include the first-order spin
      orbit interaction. We also find these systems to be very anisotropic in all their
      magnetic properties. For example, the perpendicular values of g and the hyperfine
      interaction parameter are essentially zero for the ground-state doublet. For
      illustrative purposes, the discussion focuses primarily on two specific Fe(II)
      complexes: one with the bond angle alpha greater than tetrahedral and another
      with the bond angle alpha less than tetrahedral. The nature of the EPR spectra
      and hyperfine interaction of (57)Fe are discussed.

PMID- 22583046
TI  - Inbreeding-stress interactions: evolutionary and conservation consequences.
AB  - The effect of environmental stress on the magnitude of inbreeding depression has
      a long history of intensive study. Inbreeding-stress interactions are of great
      importance to the viability of populations of conservation concern and have
      numerous evolutionary ramifications. However, such interactions are
      controversial. Several meta-analyses over the last decade, combined with omic
      studies, have provided considerable insight into the generality of inbreeding
      stress interactions, its physiological basis, and have provided the foundation
      for future studies. In this review, we examine the genetic and physiological
      mechanisms proposed to explain why inbreeding-stress interactions occur. We
      specifically examine whether the increase in inbreeding depression with
      increasing stress could be due to a concomitant increase in phenotypic variation,
      using a larger data set than any previous study. Phenotypic variation does
      usually increase with stress, and this increase can explain some of the
      inbreeding-stress interaction, but it cannot explain all of it. Overall, research
      suggests that inbreeding-stress interactions can occur via multiple independent
      channels, though the relative contribution of each of the mechanisms is unknown.
      To better understand the causes and consequences of inbreeding-stress
      interactions in natural populations, future research should focus on elucidating
      the genetic architecture of such interactions and quantifying naturally occurring
      levels of stress in the wild.

PMID- 22583047
TI  - The fundamental role of competition in the ecology and evolution of mutualisms.
AB  - Mutualisms are interspecific interactions that yield reciprocal benefits. Here,
      by adopting a consumer-resource perspective, we show how considering competition
      is necessary in order to understand the evolutionary and ecological dynamics of
      mutualism. We first review the ways in which competition shapes the ecology of
      mutualisms, using a graphical framework based on resource flows rather than net
      effects to highlight the opportunities for competition. We then describe the
      known mechanisms of competition and show how it is a critical driver of the
      evolutionary dynamics, persistence, and diversification of mutualism. We argue
      that empirical and theoretical research on the ecology and evolution of
      mutualisms will jointly progress by addressing four key points: (i) the existence
      and shape of physiological trade-offs among cooperation, competition, and other
      life-history and functional traits; (ii) the capacity for individuals to express
      conditional responses to variation in their mutualistic and competitive
      environment; (iii) the existence of heritable variation for mutualistic and
      competitive traits and their potentially conditional expression; and (iv) the
      structure of the network of consumer-resource interactions in which individuals
      are embedded.

PMID- 22583048
TI  - Exploring tropical rice diseases: a reminiscence.

PMID- 22583050
TI  - Cadmium exerts its toxic effects on photosynthesis via a cascade mechanism in the
      cyanobacterium, Synechocystis PCC 6803.
AB  - Despite intense research, the mechanism of Cd(2+)  toxicity on photosynthesis is
      still elusive because of the multiplicity of the inhibitory effects and different
      barriers in plants. The quick Cd(2+)  uptake in Synechocystis PCC 6803 permits
      the direct interaction of cadmium with the photosynthetic machinery and allows
      the distinction between primary and secondary effects. We show that the CO(2) 
      dependent electron transport is rapidly inhibited upon exposing the cells to 40
      um Cd(2+)  (50% inhibition in ~15 min). However, during this time we observe only
      symptoms of photosystem I acceptor side limitation and a build of an excitation
      pressure on the reaction centres, as indicated by light-induced P700 redox
      transients, O(2)  polarography and changes in chlorophyll a fluorescence
      parameters. Inhibitory effects on photosystem II electron transport and the
      degradation of the reaction centre protein D1 can only be observed after several
      hours, and only in the light, as revealed by chlorophyll a fluorescence
      transients, thermoluminescence and immunoblotting. Despite the marked differences
      in the manifestations of these short- and long-term effects, they exhibit
      virtually the same Cd(2+)  concentration dependence. These data strongly suggest
      a cascade mechanism of the toxic effect, with a primary effect in the dark
      reactions.

PMID- 22583051
TI  - Dietary fats and coronary heart disease.
AB  - The relation of dietary fat to risk of coronary heart disease (CHD) has been
      studied extensively using many approaches, including controlled feeding studies
      with surrogate end-points such as plasma lipids, limited randomized trials and
      large cohort studies. All lines of evidence indicate that specific dietary fatty
      acids play important roles in the cause and the prevention of CHD, but total fat
      as a percent of energy is unimportant. Trans fatty acids from partially
      hydrogenated vegetable oils have clear adverse effects and should be eliminated.
      Modest reductions in CHD rates by further decreases in saturated fat are possible
      if saturated fat is replaced by a combination of poly- and mono-unsaturated fat,
      and the benefits of polyunsaturated fat appear strongest. However, little or no
      benefit is likely if saturated fat is replaced by carbohydrate, but this will in
      part depend on the form of carbohydrate. Because both N-6 and N-3 polyunsaturated
      fatty acids are essential and reduce risk of heart disease, the ratio of N-6 to N
      3 is not useful and can be misleading. In practice, reducing red meat and dairy
      products in a food supply and increasing intakes of nuts, fish, soy products and
      nonhydrogenated vegetable oils will improve the mix of fatty acids and have a
      markedly beneficial effect on rates of CHD.

PMID- 22583052
TI  - Solution NMR studies of peptide-lipid interactions in model membranes.
AB  - Many important processes in life take place in or around the cell membranes.
      Lipids have different properties regarding their membrane-forming capacities,
      their mobility, shape, size and surface charge, and all of these factors
      influence the way that proteins and peptides interact with the membrane. In order
      for us to correctly understand these interactions, we need to be able to study
      all aspects of the interplay between lipids and peptides and proteins. Solution
      state NMR offers a somewhat unique possibility to investigate structure, dynamics
      and location of proteins and peptides in bilayers. This review focuses on
      solution NMR as a tool for investigating peptide-lipid interaction, and special
      attention is given to the various membrane mimetics that are used to model the
      membrane. Examples from the field of cell-penetrating peptides and their lipid
      interactions will be given. The importance of studying lipid and peptide
      dynamics, which reflect on the effect that peptides have on bilayers, is
      highlighted, and in this respect, also the need for realistic membrane models.

PMID- 22583053
TI  - The decline of Ockham's razor.

PMID- 22583054
TI  - Self-other knowledge asymmetries in personality pathology.
AB  - OBJECTIVE: Self-reports of personality provide valid information about
      personality disorders (PDs). However, informant reports provide information about
      PDs that self-reports alone do not provide. The current article examines whether
      and when one perspective is more valid than the other in identifying PDs. METHOD:
      Using a representative sample of adults 55 to 65 years of age (N = 991; 45%
      males), we compared the validity of self- and informant (e.g., spouse, family, or
      friend) reports of the Five-Factor Model traits in predicting PD scores (i.e.,
      composite of interviewer, self-, and informant reports of PDs). RESULTS: Self
      reports (particularly of Neuroticism) were more valid than informant reports for
      most internalizing PDs (i.e., PDs defined by high Neuroticism). Informant reports
      (particularly of Agreeableness and Conscientiousness) were more valid than self
      reports for externalizing and/or antagonistic PDs (i.e., PDs defined by low
      Agreeableness and Conscientiousness). Neither report was consistently more valid
      for thought disorder PDs (i.e., PDs defined by low Extraversion). However,
      informant reports (particularly of Agreeableness) were more valid than self
      reports for PDs that were both internalizing and externalizing (i.e., PDs defined
      by high Neuroticism and low Agreeableness). CONCLUSIONS: The intrapersonal and
      interpersonal manifestations of PDs differ, and these differences influence who
      knows more about pathology.

PMID- 22583055
TI  - Comparison of 2 devices in pigs to induce hypothermia in laparoscopic orthotopic
      kidney transplant.
AB  - OBJECTIVES: To laparoscopically compare the effectiveness of 2 cooling devices
      for renal hypothermia and investigate the feasibility of laparoscopic orthotopic
      kidney transplant using a pig model. MATERIALS AND METHODS: Eight pigs were
      divided into 2 groups of 4 animals each. Laparoscopic nephrectomy and
      autotransplant were performed first on only the right kidney. One week later,
      these procedures were performed on the left kidney, while the first transplanted
      autograft was removed. After 1 more week, the left autograft was removed for
      observation. In 1 group, the silicon tube cage was used to induce hypothermia
      during laparoscopic orthotopic kidney transplant (silicon tube cage group), and
      in the other group, the plastic bag jacket was used to induce hypothermia during
      laparoscopic orthotopic kidney transplant (plastic bag jacket group). RESULTS:
      Two pigs in the silicon tube cage group survived for 7 days after the second
      autotransplant with serum creatinine levels of 210 MUmol/L and 1010 MUmol/L. One
      pig in the plastic bag jacket group survived for 5 days. The mean surface
      temperature of the grafts was maintained at 9 degrees C +/- 3 degrees C and 12
      degrees C +/- 3 degrees C in the silicon tube cage and plastic bag jacket groups
      (P = .166). Three of 6 plastic bag jacket devices were ruptured by stitches or
      instruments. The mean venous and arterial anastomotic times in the silicon tube
      cage group were significantly shorter than were those in the plastic bag jacket
      group. CONCLUSIONS: Our study shows that the silicon tube cage may be a reliable
      renal cooling device for use in laparoscopic kidney transplant and indicates the
      feasibility of laparoscopic orthotopic kidney transplant in pigs.

PMID- 22583056
TI  - Oxytocin is expressed in epidermal keratinocytes and released upon stimulation
      with adenosine 5'-[gamma-thio]triphosphate in vitro.
AB  - Oxytocin is a neuropeptide produced primarily in the hypothalamus and is best
      known for its roles in parturition and lactation. It also influences behaviour,
      memory and mental state. Recent studies have suggested a variety of roles for
      oxytocin in peripheral tissues, including skin. Here we show that oxytocin is
      expressed in human skin. Immunohistochemical studies showed that oxytocin and its
      carrier protein, neurophysin I, are predominantly localized in epidermis. RT-PCR
      confirmed the expression of oxytocin in both skin and cultured epidermal
      keratinocytes. We also show that oxytocin is released from keratinocytes after
      application of adenosine 5'-[gamma-thio]triphosphate (ATPgammaS, a stable
      analogue of ATP) in a dose-dependent manner. The ATPgammaS-induced oxytocin
      release was inhibited by removal of extracellular calcium, or by the P2X receptor
      antagonist 2',3'-O-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate (TNP-ATP).
      These results suggest that oxytocin is produced in human epidermal keratinocytes
      and is released in response to calcium influx via P2X receptors.

PMID- 22583058
TI  - Jomthonic acid , a modified amino acid from a soil-derived Streptomyces.
AB  - Jomthonic acid A (1), a new modified amino acid, was isolated from the culture
      broth of a soil-derived actinomycete of the genus Streptomyces. The structure and
      absolute configuration of 1 were determined by spectroscopic analyses and
      chemical conversion. Jomthonic acid A (1) induced differentiation of
      preadipocytes into mature adipocytes at 2-50 MUM.

PMID- 22583057
TI  - An efficient PIFA-mediated synthesis of a directly linked zinc chlorin dimer via
      regioselective oxidative coupling.
AB  - The synthesis of a directly linked zinc chlorin dimer was first achieved by a
      facile and efficient oxidative coupling of zinc chlorin monomers with
      phenyliodine bis(trifluoroacetate) (PIFA). The reaction shows high
      regioselectivity at the 20-position near the hydrogenated pyrrole ring producing
      selective dichlorin in 74% yield.

PMID- 22583059
TI  - (Ni,Mg)3Si2O5(OH)4 solid-solution nanotubes supported by sub-0.06 wt % palladium
      as a robust high-efficiency catalyst for Suzuki-Miyaura cross-coupling reactions.
AB  - (Ni(1-x),Mg(x))(3)Si(2)O(5)(OH)(4) solid-solution nanotubes (NTs) with tunable
      compositions were hydrothermally synthesized by altering the molar ratio of
      Mg(2+) to Ni(2+). The as-synthesized NTs were loaded with sub-0.06 wt % palladium
      (Pd; ~0.045 wt %) for Suzuki-Miyaura (SM) coupling reactions between iodobenzene
      or 4-iodotoluene and phenylboronic acid. The (Ni,Mg)(3)Si(2)O(5)(OH)(4)
      (Mg(2+):Ni(2+) = 1.0:1.0) NTs supported by 0.045 wt % Pd promoted the iodobenzene
      participated coupling reaction with a high yield of >99%, an excellent recycling
      catalytic performance during 10 cycles of catalysis with yields of ~99%, and also
      an extremely low Pd releasing level of ~0.02 ppm. High-activity Pd and PdO
      clusters, multitudes of dislocations, and defects and terraces contained within
      the NTs should contribute to the (Ni,Mg)(3)Si(2)O(5)(OH)(4) (Mg(2+):Ni(2+) =
      1.0:1.0) NTs supported by 0.045 wt % Pd as a robust, reusable, and high
      efficiency catalyst for SM coupling reactions with an extremely low Pd releasing
      level. The present hydrothermally stable (Ni,Mg)(3)Si(2)O(5)(OH)(4)
      (Mg(2+):Ni(2+) = 1.0:1.0) solid-solution silicate NTs provided an ideal
      alternative tubular-structured support for noble- or transition-metal catalysts
      with low Pd loading, good recycling, and extremely low ppb levels of Pd release,
      which could also be extended to some other SM coupling reactions.

PMID- 22583060
TI  - Combining experts' judgments: comparison of algorithmic methods using synthetic
      data.
AB  - Expert judgment (or expert elicitation) is a formal process for eliciting
      judgments from subject-matter experts about the value of a decision-relevant
      quantity. Judgments in the form of subjective probability distributions are
      obtained from several experts, raising the question how best to combine
      information from multiple experts. A number of algorithmic approaches have been
      proposed, of which the most commonly employed is the equal-weight combination
      (the average of the experts' distributions). We evaluate the properties of five
      combination methods (equal-weight, best-expert, performance, frequentist, and
      copula) using simulated expert-judgment data for which we know the process
      generating the experts' distributions. We examine cases in which two well
      calibrated experts are of equal or unequal quality and their judgments are
      independent, positively or negatively dependent. In this setting, the copula,
      frequentist, and best-expert approaches perform better and the equal-weight
      combination method performs worse than the alternative approaches.

PMID- 22583061
TI  - Facilitators and hindrances in the experiences of Ugandans with and without
      disabilities when seeking access to microcredit schemes.
AB  - PURPOSE: This study aimed to identify facilitators and hindrances in the
      experiences of Ugandans with and without disabilities when seeking access to
      microcredit schemes. METHOD: Thirty-five statements were presented to 80 people,
      50 of whom were disabled. Q-methodology was used to identify factors influencing
      access to microcredit schemes. RESULTS: Running a business independently was
      solely identified by people with disabilities (PWD) as an important facilitator
      in accessing microcredit schemes, while relying on business skills was largely
      mentioned by people without disabilities. The disabled identified family-related
      items to be inhibiting factors. Having a group loan was ranked negatively by the
      disabled and ambivalently by the non-disabled. CONCLUSIONS: PWD experience
      different facilitators and barriers to access microcredit schemes compared to the
      non-disabled. PWD prefer individual loans and believe they can more successfully
      run a business on their own, instead of relying on family or having a group loan.
      Furthermore, they would benefit from microcredit schemes that take into account
      disability-specific circumstances. These are important findings to increase
      access to microcredit schemes and to let PWD benefit to the same extend from
      these programmes than do their non-disabled peers.

PMID- 22583063
TI  - Assimilating evidence quality at a glance using graphic display: research
      synthesis on labor induction.
AB  - Evidence profiled in the World Health Organization induction of labor guideline
      extended to 84 tables and 116 pages, which is hard to assimilate. Summarizing
      this evidence graphically can present information on key outcomes succinctly,
      illustrating where the gaps, strengths and weaknesses lie. For induction of
      labor, graphic representation clearly showed that evidence was lacking on
      maternal complications when comparing oxytocin with other agents, evidence was
      strong on birth within 24 h when comparing vaginal prostaglandins with placebo or
      no treatment, but again it was weak on uterine hyperstimulation when comparing
      oxytocin with vaginal prostaglandins. These graphs/plots allow readers to capture
      the essence of the information gathered at a glance. The use of graphical
      displays when interpreting and publishing data on several comparisons and
      outcomes is encouraged.

PMID- 22583064
TI  - Inhibition of beef isolates of E. coli O157:H7 by orange oil at various
      temperatures.
AB  - Plant essential oils have previously been shown to exhibit antimicrobial
      activities against various microorganisms. In this study, cold pressed
      terpeneless Valencia orange oil (CPTVO) was examined at various temperatures (37,
      10, and 4  degrees C) to determine its antimicrobial activity against 3 strains
      of E. coli O157:H7 recovered from beef products. A micro broth dilution method
      using 96 well microtiter plates was used with trypticase soy broth with 0.15%
      agar and 2,3,5 tetrazolium chloride as a growth indicator as the medium. Serial
      dilutions of CPTVO were made, resulting in final concentrations of oil ranging
      from 0.2% to 25% or 0.1% to 10%. Plates were incubated statically at 4, 10, or 37
      degrees C, and sampled hourly. After 6 h at 37  degrees C, all strains were
      inhibited at concentrations ranging from 0.2% to 0.6%, with a mean of 0.4 +/-
      0.01%. At 10  degrees C, all strains were inhibited at concentrations ranging
      from 0.8% to 6.3%, with a mean of 1.1% +/- 0.2%, after 6 h. At 4  degrees C, all
      strains were inhibited after 6 h at concentrations ranging from 2.3% to 4.6%,
      with a mean of 3.5% +/- 2.1%. After 24 h at 4  degrees C the strains were
      inhibited at concentrations ranging from 0.7% to 1% with a mean of 0.8% +/- 0.3%.
      The ranges appear to be the result of effects from the variable nature of a
      complex media and an antimicrobial that presents potential multiple mechanisms
      for inhibition. It appears CPTVO is a viable option to inhibit E. coli O157:H7
      growth at refrigeration temperatures. PRACTICAL APPLICATION: Beef products are
      often the source of foodborne illness from the organism E. coli O157:H7. Orange
      essential oils have been in the human diet for centuries, and the research
      reported here indicates that some of these oils may be used as surface
      applications during cold temperatures to inhibit the foodborne pathogen E. coli
      O157:H7.

PMID- 22583065
TI  - Cost-effectiveness of fingolimod versus interferon beta-1a for relapsing
      remitting multiple sclerosis in the United States.
AB  - OBJECTIVE: Fingolimod has been shown to be more efficacious than interferon (IFN)
      beta-1a, but at a higher drug acquisition cost. The aim of this study was to
      assess the cost-effectiveness of fingolimod compared to IFN beta-1a in patients
      diagnosed with relapsing-remitting multiple sclerosis (RRMS) in the US. METHODS:
      A Markov model comparing fingolimod to intramuscular IFN beta-1a using a US
      societal perspective and a 10-year time horizon was developed. A cohort of 37
      year-old patients with RRMS and a Kurtzke Expanded Disability Status Scale score
      of 0-2.5 were assumed. Data sources included the Trial Assessing Injectable
      Interferon vs FTY720 Oral in Relapsing-Remitting Multiple Sclerosis (TRANSFORMS)
      and other published studies of MS. Outcomes included costs in 2011 US dollars,
      quality-adjusted life years (QALYs), number of relapses avoided, and incremental
      cost-effectiveness ratios (ICERs). RESULTS: Compared to IFN beta-1a, fingolimod
      was associated with fewer relapses (0.41 vs 0.73 per patient per year) and more
      QALYs gained (6.7663 vs 5.9503), but at a higher cost ($565,598 vs $505,234).
      This resulted in an ICER of $73,975 per QALY. Results were most sensitive to
      changes in drug costs and the disutility of receiving IFN beta-1a. Monte Carlo
      simulation demonstrated fingolimod was cost-effective in 35% and 70% of 10,000
      iterations, assuming willingness-to-pay thresholds of $50,000 and $100,000 per
      QALY, respectively. LIMITATIONS: Event rates were primarily derived from a single
      randomized clinical trial with 1-year duration of follow-up and extrapolated to a
      10-year time horizon. Comparison was made to only one disease-modifying drug
      intramuscular IFN beta-1a. CONCLUSION: Fingolimod use is not likely to be cost
      effective compared to IFN beta-1a unless fingolimod cost falls below $3476 per
      month or a higher than normal willingness-to-pay threshold is accepted by
      decision-makers.

PMID- 22583066
TI  - Formation of beta-cyclodextrin inclusion enhances the stability and aqueous
      solubility of natural borneol.
AB  - The aims of this study were to optimize the preparation conditions of natural
      borneol/beta-cyclodextrin (NB/beta-CD) inclusion complex by ultrasound method,
      and to investigate its improvement of stability and solubility. The complex was
      characterized by different various spectroscopic techniques including Fourier
      transform infrared spectroscopy, X-ray diffractometry, and differential scanning
      calorimetry. The results demonstrate that NB could be efficiently loaded into
      beta-CD to form an inclusion complex by ultrasound method at a molar ratio of 1:
      1and mass ratio of 1: 6. The complex exhibited different physicochemical
      characteristics from that of free NB. Typically, formation of beta-CD inclusion
      significantly enhanced the stability and aqueous solubility of NB. PRACTICAL
      APPLICATION: Natural borneol (NB) has the potential to be widely used in the
      fields of medical and functional food, due to its specificity. However, the
      disadvantages of unstability in the preparation and storage process due to its
      easy sublimation and the low water solubility limit its application. This
      research provides an effective way to improve the solubility and stability of NB
      by preparing NB/beta-CD inclusion complex. Furthermore, theoretical basis is also
      provided for the application development of NB.

PMID- 22583067
TI  - The role of risk perception in explaining parental sunscreen use.
AB  - OBJECTIVE: This study assessed: (1) whether risk perceptions about skin cancer
      were related to parent's use of sunscreen on their children; (2) which
      combination of assessments susceptibility and severity best explain parental
      sunscreen protection behaviours and (3) whether risk perceptions influence
      behaviour directly through intentions or through attitudes, subjective norms and
      self-efficacy. DESIGN: Two longitudinal studies assessed sunscreen protection
      behaviours of parents for their toddlers (N = 391) and young children (N = 436).
      MAIN OUTCOME MEASURE: Parent's use of sunscreen on their children. RESULTS: Risk
      perceptions correlated with future sunscreen protection behaviours of parents but
      were lower than those of attitude, social influence and self-efficacy. Treating
      susceptibility and severity as an additive function resulted in the best model
      fit. Risk perceptions were related with future intention and future sunscreen
      protection behaviour, but the effects were mediated through attitude, social
      influence and self-efficacy. CONCLUSIONS: Our path analyses suggest treating
      susceptibility and severity as an additive function. A multiplicative model
      without main effects - although often used - had the poorest fit. Risk
      perceptions influence behaviour by influencing attitudinal and self-efficacy
      beliefs. Addressing risk perceptions in health communication programs is relevant
      when the purpose is to increase awareness and to influence attitudes and self
      efficacy.

PMID- 22583068
TI  - An ICD lead advisory: a plea for more diligence and more data.

PMID- 22583069
TI  - NI-1: a novel canine mastocytoma model for studying drug resistance and IgER
      dependent mast cell activation.
AB  - BACKGROUND: Advanced mast cell (MC) disorders are characterized by uncontrolled
      growth of neoplastic MC in various organs, mediator-related symptoms, and a poor
      prognosis. Kit mutations supposedly contribute to abnormal growth and drug
      resistance in these patients. METHODS: We established a novel canine mastocytoma
      cell line, NI-1, from a patient suffering from MC leukemia. RESULTS: NI-1 cells
      were found to form mastocytoma lesions in NOD/SCID IL-2Rgamma(null) mice and to
      harbor several homozygous Kit mutations, including missense mutations at
      nucleotides 107(C->T) and 1187(A->G), a 12-bp duplication (nucleotide 1263), and
      a 12-bp deletion (nucleotide 1550). NI-1 cells expressed several MC
      differentiation antigens, including tryptase, Kit, and a functional IgE receptor.
      Compared to the C2 mastocytoma cell line harboring a Kit exon 11 mutation, NI-1
      cells were found to be less responsive against the Kit tyrosine kinase inhibitors
      (TKI) masitinib and imatinib, but were even more sensitive against proliferation
      inhibitory effects of the mammalian target of rapamycin (mTOR) blocker RAD001 and
      PI3-kinase/mTOR blocker NVP-BEZ235. The Kit-targeting multikinase inhibitors
      PKC412 and dasatinib were also found to override TKI resistance in NI-1 cells,
      and produced growth inhibition with reasonable IC(50) values (<0.1 MUM).
      CONCLUSION: NI-1 may serve as a useful tool to investigate IgE-dependent
      reactions and mechanisms of abnormal growth and drug resistance in neoplastic MC
      in advanced mastocytosis.

PMID- 22583070
TI  - Treatment with anti-inflammatory drugs in community-acquired pneumonia.
AB  - Pneumonia exhibits a broad range of severity, from mildly symptomatic at one end
      to fulminant septic shock and death at the other. Although an adequate
      inflammatory response is necessary for the clearance of microorganisms, excessive
      inflammation can lead to ongoing local and systemic damage. Because of this
      extended inflammatory response despite appropriate antibiotic therapy, as well as
      increasing antibiotic resistance, adjuvant therapy for pneumonia that can
      favourably modify the immune response has become an increasingly relevant
      approach to improve prognosis. Different adjuvant treatment options for pneumonia
      have recently been proposed. Promising treatment options include corticosteroids,
      statins, macrolides and Toll-like receptor antagonists. The aim of this review is
      to summarize the inflammatory response during pneumonia and discuss the current
      knowledge and future perspectives regarding the anti-inflammatory treatment
      options for patients with pneumonia.

PMID- 22583071
TI  - Hydrogen generation catalyzed by fluorinated diglyoxime-iron complexes at low
      overpotentials.
AB  - Fe(II) complexes containing the fluorinated ligand 1,2-bis(perfluorophenyl)ethane
      1,2-dionedioxime (dAr(F)gH(2); H = dissociable proton) exhibit relatively
      positive Fe(II/I) reduction potentials. The air-stable difluoroborated species
      [(dAr(F)gBF(2))(2)Fe(py)(2)] (2) electrocatalyzes H(2) generation at -0.9 V vs
      SCE with i(cat)/i(p) ~ 4, corresponding to a turnover frequency (TOF) of ~20 s(
      1) [Faradaic yield (FY) = 82 +/- 13%]. The corresponding monofluoroborated,
      proton-bridged complex [(dAr(F)g(2)H-BF(2))Fe(py)(2)] (3) exhibits an improved
      TOF of ~200 s(-1) (i(cat)/i(p) ~ 8; FY = 68 +/- 14%) at -0.8 V with an
      overpotential of 300 mV. Simulations of the electrocatalytic cyclic voltammograms
      of 2 suggest rate-limiting protonation of an Fe("0") intermediate (k(RLS) ~ 200
      M(-1) s(-1)) that undergoes hydride protonation to form H(2). Complex 3 likely
      reacts via protonation of an Fe(I) intermediate that subsequently forms H(2) via
      a bimetallic mechanism (k(RLS) ~ 2000 M(-1) s(-1)). 3 catalyzes production at
      relatively positive potentials compared with other iron complexes.

PMID- 22583073
TI  - Plant pathology at the crossroads.

PMID- 22583072
TI  - Delusional infestation and the specimen sign: a European multicentre study in 148
      consecutive cases.
AB  - BACKGROUND: Systematic studies of delusional infestation (DI), also known as
      delusional parasitosis, are scarce. They lack either dermatological or
      psychiatric detail. Little is known about the specimens that patients provide to
      prove their infestation. There is no study on the current presentation of DI in
      Europe. OBJECTIVES: To determine the number of true infestations, to assess with
      which pathogens patients believe themselves to be infested, and to gather details
      about the frequency and nature of the specimens and the containers used to store
      them, based on European study centres. METHODS: Retrospective study of
      consecutive cases with suspected DI from six centres (Dermatology, Psychiatry,
      Tropical Medicine) in four European countries (U.K., Germany, Italy, France).
      RESULTS: In total, 148 consecutive cases of suspected DI were included, i.e. the
      largest cohort reported. None of the patients had evidence of a genuine
      infestation, as shown by examinations by dermatologists and/or infectious disease
      specialists. Only 35% believed themselves to be infested by parasites; the
      majority reported a large number of other living or inanimate (17%) pathogens.
      Seventy-one patients (48%) presented with what they believed was proof of their
      infestation. These specimens were mostly skin particles or hair, and rarely
      insects (only very few of which were human pathogenic or anthropophilic, and none
      of these could be correlated with the clinical presentation), and only 4% were
      stored in matchboxes (three of 71). CONCLUSIONS: This first multicentre study of
      DI in Europe confirms that the term 'delusional infestation' better reflects
      current and future variations of this entity than 'delusional parasitosis'. The
      presentation of proofs of infestation, commonly referred to as 'the matchbox
      sign', is typical but not obligatory in DI and might better be called 'the
      specimen sign'.

PMID- 22583074
TI  - The two pathways to being an (un-)popular narcissist.
AB  - OBJECTIVE: Narcissism affects social relationships from the very first
      interactions. The overall positivity of social impressions narcissists evoke is,
      however, unclear-with previous research reporting positive, negative, or null
      effects on popularity at short-term acquaintance. Here we postulate a dual
      pathway model, which explains the effects of narcissism on (un-)popularity as the
      result of two opposing behavioral pathways: assertiveness and aggressiveness.
      METHOD: In two studies, unacquainted German college students (N = 100; N = 68)
      met in groups of four to six persons and engaged in group discussions. Afterward,
      they provided ratings of each other's assertiveness, aggressiveness, and
      likeability. In Study 2, we additionally videotaped the sessions and assessed
      participants' actual behavior. RESULTS: Results of both studies confirm our dual
      pathway hypothesis: There was a "positive" and a "negative" path from targets'
      narcissism to being liked or not-dependent upon being seen as assertive or
      aggressive. Behavioral observations showed that expressive and dominant behaviors
      mediated the positive path, whereas arrogant and combative behaviors mediated the
      negative path. CONCLUSIONS: Initial (un-)popularity of narcissists at early
      stages of interpersonal interactions depends on the behavioral pathway that is
      triggered in the given situational context.

PMID- 22583075
TI  - Rural Nevada and climate change: vulnerability, beliefs, and risk perception.
AB  - In this article, we present the results of a study investigating the influence of
      vulnerability to climate change as a function of physical vulnerability,
      sensitivity, and adaptive capacity on climate change risk perception. In
      2008/2009, we surveyed Nevada ranchers and farmers to assess their climate change
      related beliefs, and risk perceptions, political orientations, and socioeconomic
      characteristics. Ranchers' and farmers' sensitivity to climate change was
      measured through estimating the proportion of their household income originating
      from highly scarce water-dependent agriculture to the total income. Adaptive
      capacity was measured as a combination of the Social Status Index and the Poverty
      Index. Utilizing water availability and use, and population distribution GIS
      databases; we assessed water resource vulnerability in Nevada by zip code as an
      indicator of physical vulnerability to climate change. We performed correlation
      tests and multiple regression analyses to examine the impact of vulnerability and
      its three distinct components on risk perception. We find that vulnerability is
      not a significant determinant of risk perception. Physical vulnerability alone
      also does not impact risk perception. Both sensitivity and adaptive capacity
      increase risk perception. While age is not a significant determinant of it,
      gender plays an important role in shaping risk perception. Yet, general beliefs
      such as political orientations and climate change-specific beliefs such as
      believing in the anthropogenic causes of climate change and connecting the
      locally observed impacts (in this case drought) to climate change are the most
      prominent determinants of risk perception.

PMID- 22583076
TI  - Mucormycosis extending from the surgical wound to the transplanted kidney: case
      report and literature review.
AB  - Mucormycosis is an opportunistic, life-threatening infection in organ transplant
      recipients. We report a case of surgical wound mucormycosis that extended to a
      transplanted kidney. The patient was a 59-year-old man who underwent a donation
      after-cardiac-death kidney transplant 10 years after receiving a liver
      transplant. On day 10 after the kidney transplant, he presented with cutaneous
      and subcutaneous tissues necrotizing at his right lower abdominal surgical wound.
      The necrotic tissue biopsy and laboratory culture showed different causes, while
      a polymerase chain reaction quickly identified the causative fungus at the
      species level. Although the combination therapy consisted of immunosuppressant
      withdrawal, intravenous Liposome AmB, and aggressive surgical debridement;
      unfortunately, the cutaneous mucormycosis invaded his transplanted kidney, and
      the patient was given a graft nephrectomy and subsequent hemodialysis.  We review
      the literature and conclude that mucormycosis in organ transplant recipients is a
      rare and extremely severe complication. Polymerase chain reaction provides a
      rapid and accurate diagnostic technique for species identification. Early
      effective antifungal therapy combined with aggressive surgical intervention and
      judicious withdrawal of immunosuppressants appears to be indispensable for a
      favorable outcome.

PMID- 22583077
TI  - Therapy management of cardiovascular adverse events in the context of targeted
      therapy for metastatic renal cell carcinoma.
AB  - Targeted agents have significantly improved outcomes in patients with metastatic
      renal cell carcinoma, and are changing long-term expectations in these patients.
      Experience with these agents highlights a distinct safety and tolerability
      profile, differing from that observed with conventional chemotherapy and
      radiotherapy. Cardiovascular adverse events have been observed when treating with
      targeted agents. This is of particular importance for patients with metastatic
      renal cell carcinoma who are elderly and present with significant comorbidities.
      A multidisciplinary approach and close collaboration between oncologists and
      cardiologists is essential for optimal management of cardiovascular adverse
      events. Strategies for the management of these adverse events include assessment
      of cardiovascular status at baseline and at regular intervals, patient education,
      and the use of supportive medication. Effective therapy management allows
      patients with cardiovascular adverse events to receive and continue targeted
      therapy with careful monitoring. Implementation of therapy management measures
      contributes towards maximizing treatment outcomes with targeted agents in
      patients with metastatic renal cell carcinoma.

PMID- 22583078
TI  - Corticosteroid treatment selectively decreases mast cells in the smooth muscle
      and epithelium of asthmatic bronchi.
AB  - BACKGROUND: Mast cells are important in the pathophysiology of airway
      inflammation and evidence suggests their sub-localisation within the airway is
      altered in asthma. Little is known about the effect of corticosteroids on mast
      cell localisation within the bronchi. METHODS: We therefore performed an
      immunohistochemical analysis of mast cell numbers within the smooth muscle,
      epithelium and submucosa of healthy subjects (n = 10) and well-characterised
      asthmatic patients, using either beta(2)-agonists alone (n = 10) or beta(2)
      agonists and inhaled corticosteroids (n = 10). RESULTS: Patients using inhaled
      corticosteroids displayed significantly lower numbers of mast cells within their
      epithelium and smooth muscle compared to those not treated with inhaled
      corticosteroids. Submucosal mast cells were not affected by corticosteroid
      treatment. Numbers of smooth muscle mast cells correlated with bronchial
      responsiveness and epithelial mast cells with exhaled NO. CONCLUSION: We
      demonstrate that glucocorticosteroids differentially affect mast cell numbers
      within specific airway sub-locations highlighting the importance of mast cell and
      smooth muscle/epithelial interactions in asthma pathogenesis.

PMID- 22583079
TI  - Cytotoxic metabolites from the antarctic psychrophilic fungus Oidiodendron
      truncatum.
AB  - Two new epipolythiodioxopiperazines, named chetracins B and C (1 and 2), and five
      new diketopiperazines, named chetracin D (4) and oidioperazines A-D (5, 10, 12,
      and 13), were isolated from the fungus Oidiodendron truncatum GW3-13, along with
      six known compounds (3, 6, 7, 8, 9, and 11). Their structures were elucidated by
      extensive NMR, MS, and CD analyses, as well as chemical transformation. An in
      vitro MTT cytotoxicity assay revealed potent biological activity for 1 in the
      nanomolar range against a panel of five human cancer lines.

PMID- 22583080
TI  - Carbon-carbon bond formation via the electrophilic addition of carbocations to
      allenes.
AB  - A novel electrophilic addition of aryl-substituted allenes and carbocations
      forming a carbon-carbon bond is described. Stereodefined allylic halides and
      indenes were furnished with excellent regio- and stereoselectivity depending on
      the structure of allenes.

PMID- 22583081
TI  - Childbirth attendance strategies and their impact on maternal mortality and
      morbidity in low-income settings: a systematic review.
AB  - OBJECTIVE: To review quantitative evidence of the effect on maternal health of
      different childbirth attendance strategies in low-income settings. DESIGN:
      Systematic review. METHODS: Studies using quantitative methods, referring to the
      period 1987-2011, written in English and reporting the impact of childbirth
      attendance strategies on maternal mortality or morbidity in low-income settings
      were included. Guidelines developed by the Cochrane collaboration and the Centre
      for Review and Dissemination, University of York were followed. The included
      articles were read and sorted by category of strategy that emerged from the
      reading. RESULTS: The search criteria yielded 29 articles. The following three
      main categories of strategy emerged: (i) those primarily intended to improve
      quality of care; (ii) "centrifugal strategies," which sought to bring services to
      the women; and (iii) "centripetal strategies," which sought to bring the women to
      the services. Few of the studies had a design that provided strong evidence for
      the impact of the strategy concerned. CONCLUSIONS: The evidence emerging from the
      studies was difficult to compare, because concepts were not defined in a
      consistent manner (such as "skilled birth attendance") and many studies examined
      the impact of a package of interventions without ferreting out the impact of
      individual components. Yet, some studies described individual aspects with great
      promise (such as cost, transport, outreach-friendly drugs or targeted training).
      There is a need for clearer conceptual frameworks, including some which permit
      assessment of packages of interventions.

PMID- 22583082
TI  - Walking tests for stroke survivors: a systematic review of their measurement
      properties.
AB  - PURPOSE: To provide an overview of walking tests including their measurement
      properties that have been used in stroke survivors. METHOD: Electronic databases
      were searched using specific search strategies. Retrieved studies were selected
      by using specified inclusion criteria. A modified consensus-based standards for
      the selection of health status measurement instruments (COSMIN) checklist was
      applied for methodological quality assessment of the included studies. A quality
      assessment for statistical outcomes was used to assess measurement properties of
      the walking tests. Tests that were included were categorized according to the
      framework of the international classification of functioning, disability and
      health (ICF). RESULTS: Thirty-two studies, evaluating 23 walking tests, were
      included. The tests assessed walking using the outcome measures of walking speed,
      walking distance, functional ambulation and walking on different surfaces. The
      methodological design and statistical methods of most studies evaluating
      reliability and criterion validity were sufficient, and found the outcome
      measures to be reliable and valid. However, data on measurement error, minimal
      important difference and minimal important change were lacking and responsiveness
      was correctly evaluated in one study only. CONCLUSIONS: Many walking tests have
      been clinimetrically evaluated in stroke survivors. Most walking tests were found
      to be reliable and valid.

PMID- 22583084
TI  - Mediation analysis of the association between use of NRT for smoking reduction
      and attempts to stop smoking.
AB  - OBJECTIVES: Use of nicotine replacement therapy (NRT) for smoking reduction (SR)
      is linked to higher quit attempt rates than SR without NRT. This study aimed to
      assess the possible mediating roles of confidence in ability to quit, enjoyment
      of smoking and motivation to quit in this association. DESIGN: Cross-sectional
      survey. MAIN OUTCOME MEASURES: Smokers were asked if they were currently
      attempting SR, and if they were, whether they were using NRT. Motivation to stop,
      enjoyment of smoking, confidence in ability to stop, and previous quit attempts,
      were also assessed. RESULTS: There was no evidence that confidence in ability to
      quit or enjoyment of smoking mediated the association between the use of NRT for
      SR and attempts to quit. Only motivation to stop partially mediated between the
      use of NRT for SR and attempts to stop (indirect effect: odds ratio 1.08, p <
      0.001). CONCLUSION: Although this study is limited by its cross-sectional design,
      the findings point towards the possibility that the use of NRT to aid SR may
      promote attempts to stop through increasing motivation to quit but not by
      increasing confidence or by reducing enjoyment of smoking. Longitudinal studies
      are required to draw firmer conclusions about the possible mediating effects of
      motivation to quit.

PMID- 22583083
TI  - Regulation of KCNQ1/KCNE1 by beta-catenin.
AB  - beta-catenin, a multifunctional protein expressed in all tissues including the
      heart stimulates the expression of several genes important for cell
      proliferation. Signaling involving beta-catenin participates in directing cardiac
      development and in the pathophysiology of cardiac hypertrophy. Nothing is known,
      however, on the role of beta-catenin in the regulation of cardiac ion channels.
      The present study explored the functional interaction of beta-catenin and
      KCNE1/KCNQ1, the K+ channel complex underlying the slowly activating outwardly
      rectifying K+ current. To this end, KCNE1/KCNQ1 was expressed in Xenopus oocytes
      with and without beta-catenin and the depolarization (up to + 80 mV) induced
      current (I(Ks)) was determined using the two-electrode voltage clamp. As a
      result, beta-catenin enhanced I(Ks) by 30%. The effect of beta-catenin on I(Ks)
      was not affected by actinomycin D (10 MUM), an inhibitor of transcription,
      indicating that beta-catenin was not effective as transcription factor. Confocal
      microscopy revealed that beta-catenin enhanced the KCNE1/KCNQ1 protein abundance
      in the cell membrane. Exposure of the oocytes to brefeldin A (5 MUM), an
      inhibitor of vesicle insertion, was followed by a decline of I(Ks), which was
      then similar in oocytes expressing KCNE1/KCNQ1 together with beta-catenin and in
      oocytes expressing KCNE1/KCNQ1 alone. In conclusion, beta-catenin enhances I(Ks)
      by increasing the KCNE1/KCNQ1 protein abundance in the cell membrane, an effect
      requiring vesicle insertion into the cell membrane.

PMID- 22583085
TI  - Diagnostic and therapeutic dilemma associated with atypical glandular cells on
      liquid-based cervical cytology.
AB  - BACKGROUND: In 2008, the management of women in Ireland with atypical glandular
      cells changed to immediate referral to colposcopy. The optimal management of
      these women is unclear. A balance between the detection of occult disease and
      overtreatment is required. METHODS: Our study aim was to document the experience
      of this policy at the National Maternity Hospital, Dublin. Information from the
      computerized data management system was analysed with the statistical package
      SPSS. RESULTS: In 2009, 156 women attended colposcopy following a single atypical
      glandular cell diagnosis on liquid-based cytology. The mean age was 41 years.
      Thirty (19.2%) women had abnormal vaginal bleeding, 31 (19.9%) were smokers and
      34 (21.8%) had received previous treatment. The colposcopy was satisfactory in
      125 (80.1%) and unsatisfactory in 31 (19.9%). Cervical histology was available
      for 146 (93.6%) women: 57 excisional procedures and 89 diagnostic biopsies.
      Abnormal histology was detected in 46 women (31.5%). Four women (2.7%) had
      invasive cancer, five (3.4%) had adenocarcinoma in situ, 21 (14.4%) had cervical
      intraepithelial neoplasia (CIN) grade 2 or 3 and 16 (11.0%) had CIN1. No
      abnormality was detected in 100 women (68.5%), including 35 (61.4%) of those who
      had undergone excisional procedures. The colposcopic impression in this group was
      unsatisfactory in 10 women (28.6%), glandular abnormalities in six (17.1%), high-
      and low-grade changes in 12 (34.2%) and six (17.1%) women, respectively, and
      normal in one (2.9%). The findings were essentially negative in the remaining 10
      women: overall, 30 (19.2%) of the 156 women referred to colposcopy had at least
      CIN2. CONCLUSION: This study confirmed significant levels of high-grade disease
      in women referred to colposcopy with atypical glandular cells on cytology.
      Concerns about undetected endocervical disease resulted in high levels of
      negative excisional biopsies. Alternative strategies, including endometrial
      sampling, human papillomavirus testing and discussion at clinicopathological
      meeting, should be considered.

PMID- 22583087
TI  - Achievement goals as mediators of the relationship between competence beliefs and
      test anxiety.
AB  - BACKGROUND: Previous work suggests that the expectation of failure is related to
      higher test anxiety and achievement goals grounded in a fear of failure. AIM: To
      test the hypothesis, based on the work of Elliot and Pekrun (2007), that the
      relationship between perceived competence and test anxiety is mediated by
      achievement goal orientations. SAMPLE: Self-report data were collected from 275
      students in post-compulsory education following courses in A Level Psychology.
      RESULTS: Competence beliefs were inversely related to the worry and tension
      components of test anxiety, both directly and indirectly through a performance
      avoidance goal orientation. A mastery-avoidance goal orientation offered an
      indirect route from competence beliefs to worry only. CONCLUSION: These findings
      provide partial support for Elliot and Pekrun's (2007) model. Although
      significant mediating effects were found for mastery-avoidance and performance
      avoidance goals, they were small and there may be other mechanisms to account for
      the relations between competence beliefs and test anxiety.

PMID- 22583086
TI  - Gender differences in teachers' perceptions of students' temperament, educational
      competence, and teachability.
AB  - BACKGROUND: Student's temperament plays a significant role in teacher's
      perception of the student's learning style, educational competence (EC), and
      teachability. Hence, temperament contributes to student's academic achievement
      and teacher's subjective ratings of school grades. However, little is known about
      the effect of gender and teacher's age on this association. AIMS: We examined the
      effect of teacher's and student's gender and teacher's age on teacher-perceived
      temperament, EC, and teachability, and whether there is significant same gender
      or different gender association between teachers and students in this
      relationship. SAMPLE: The participants were population-based sample of 3,212
      Finnish adolescents (M= 15.1 years) and 221 subject teachers. METHODS:
      Temperament was assessed with Temperament Assessment Battery for Children -
      Revised and Revised Dimensions of Temperament Survey batteries and EC with three
      subscales covering Cognitive ability, Motivation, and Maturity. Data were
      analyzed with multi-level modelling. RESULTS: Teachers perceived boys'
      temperament and EC more negatively than girls'. However, the differences between
      boys and girls were not as large when perceived by male teachers, as they were
      when perceived by female teachers. Males perceived boys more positively and more
      capable in EC and teachability than females. They were also stricter regarding
      their perceptions of girls' traits. With increasing age, males perceived boys'
      inhibition as higher and mood lower. Generally, the older the teacher, the more
      mature he/she perceived the student. CONCLUSIONS: Teachers' ratings varied
      systematically by their gender and age, and by students' gender. This bias may
      have an effect on school grades and needs be taken into consideration in teacher
      education.

PMID- 22583088
TI  - Individual and social network predictors of the short-term stability of bullying
      victimization in the United Kingdom and Germany.
AB  - BACKGROUND: There is still relatively little research on the social context
      within which bullying develops and remains stable. AIM: This study examined the
      short-term stability of bullying victimization among primary school students in
      the United Kingdom and Germany (mean age, 8.9 years) and the individual and
      social network factors that contributed to remaining a victim of bullying.
      SAMPLE: The sample consisted of 454 children (247 males and 207 females).
      METHODS: Participants completed questionnaires on bullying victimization at three
      assessment points over a 9-week period. Other measures consisted of self-reported
      demographic, peer, and family relationship characteristics. Social network
      indices of density, reciprocity, and hierarchy were constructed using friendship
      and peer acceptance nominations. RESULTS: Relative risk analyses indicated a six
      fold increased risk of remaining a victim at consequent follow-ups, compared to a
      child not victimized at baseline becoming a victim over the follow-up period.
      Individual characteristics explained substantially more variance in the stability
      of bullying victimization than class-level factors. Hierarchical logistic
      regression analyses revealed that being victimized by siblings and being rejected
      by peers predicted remaining a victim over a 9-week period. CONCLUSIONS: Bullying
      victimization among primary school students proved moderately stable over a 9
      week period. Individual characteristics were more influential in predicting the
      stable victim role than class-level factors. Our findings have implications for
      the identification of stable victims in primary school and early preventative
      bullying programs.

PMID- 22583089
TI  - The influence of norms and social identities on children's responses to bullying.
AB  - BACKGROUND: Research on bullying increasingly focuses on social processes,
      showing that group membership affects children's responses to bullying scenarios.
      Additionally, correlational research has shown links between norms of cooperation
      and prosocial behaviour, and between competition and more aggressive forms of
      behaviour. AIMS: This paper focuses on how children's peer group membership
      affects their group-based emotions in response to an intergroup bullying
      incident, and the action tendencies that these emotions predict, in the context
      of different background norms (for competitive or cooperative behaviour). SAMPLE:
      Italian schoolchildren, 10-13 years old (N= 128, 65 males) took part in this
      study. METHODS: Participants were randomly assigned to the group of a
      perpetrator, target, or third-party group member described in a scenario. Next,
      they played a game designed to induce a cooperative, competitive, or neutral
      norm, and read the scenario. They then answered a questionnaire measuring their
      group-based emotions. RESULTS: Results underscored the role of norms and group
      processes in responses to bullying. In particular, children exposed to a
      cooperative norm expressed less pride and more regret and anger about the
      bullying than those in other conditions. CONCLUSIONS: This study indicates that
      the influence peer groups have on bullying may be tempered by the introduction of
      a cooperative normative context to the school setting.

PMID- 22583090
TI  - Improving text recall with multiple summaries.
AB  - BACKGROUND: QuikScan (QS) is an innovative design that aims to improve
      accessibility, comprehensibility, and subsequent recall of expository text by
      means of frequent within-document summaries that are formatted as numbered list
      items. The numbers in the QS summaries correspond to numbers placed in the body
      of the document where the summarized ideas are discussed in full. AIM: To examine
      the influence of QS summaries on participants' perceptions of text quality (i.e.,
      comprehensibility, structure, and interest) and recall, an experimental - control
      group design compared the effects of a QS text with a structured abstract (SA)
      text. SAMPLE: Forty psychology students participated voluntarily or received
      course credits. METHOD: Students first read a control (SA) or experimental (QS)
      text on flashbulb memory (FBM). Next, their perceptions of text quality were
      measured through a questionnaire. Recall was assessed with an open answer test
      with items for facts, comprehension and higher order information. RESULTS:
      Perceptions of text quality did not vary across conditions. But QS did lead to
      significantly and substantially (d= 1.57) higher overall recall scores.
      Participants with the QS text performed significantly better on all item types
      than participants with the SA text. CONCLUSION: Studying a QS text led to a
      substantial improvement in recall compared to an SA text. Further research is
      needed to examine how readers study QS texts and whether a text model hypothesis
      or a repetition effect hypothesis accounts for the effectiveness. The first
      hypothesis posits that the QS summaries support the reader in constructing a text
      schema. The second attributes the effects of these summaries to their repetition
      of text topics.

PMID- 22583091
TI  - Teacher beliefs, teacher characteristics, and school contextual factors: what are
      the relationships?
AB  - BACKGROUND: There is a plethora of research around student beliefs and their
      contribution to student outcomes. However, there is less research in relation to
      teacher beliefs. Teacher factors are important to consider since beliefs mould
      thoughts and resultant instructional behaviours that, in turn, can contribute to
      student outcomes. AIMS: The purpose of this research was to explore relationships
      between the teacher characteristics of gender and teaching experience, school
      contextual variables (socio-economic level of school and class level), and three
      teacher socio-psychological variables: class level teacher expectations, teacher
      efficacy, and teacher goal orientation. SAMPLE: The participants were 68 male and
      female teachers with varying experience, from schools in a variety of socio
      economic areas and from rural and urban locations within New Zealand. METHOD:
      Teachers completed a questionnaire containing items related to teacher efficacy
      and goal orientation in reading. They also completed a teacher expectation
      survey. Reading achievement data were collected on students. Interrelationships
      were explored between teacher socio-psychological beliefs and the teacher and
      school factors included in the study. RESULTS: Mastery-oriented beliefs predicted
      teacher efficacy for student engagement and classroom management. The socio
      economic level of the school and teacher gender predicted teacher efficacy for
      engagement, classroom management, instructional strategies, and a mastery goal
      orientation. Being male predicted a performance goal orientation. CONCLUSIONS:
      Teacher beliefs, teacher characteristics, and school contextual variables can
      result in differences in teacher instructional practices and differing classroom
      climates. Further investigation of these variables is important since differences
      in teachers contribute to differences in student outcomes.

PMID- 22583092
TI  - Dyslexia, authorial identity, and approaches to learning and writing: a mixed
      methods study.
AB  - BACKGROUND: Dyslexia may lead to difficulties with academic writing as well as
      reading. The authorial identity approach aims to help students improve their
      academic writing and avoid unintentional plagiarism, and could help to understand
      dyslexic students' approaches to writing. AIMS: (1) To compare dyslexic and non
      dyslexic students' authorial identity and approaches to learning and writing; (2)
      to compare correlations between approaches to writing and approaches to learning
      among dyslexic and non-dyslexic students; (3) to explore dyslexic students'
      understandings of authorship and beliefs about dyslexia, writing and plagiarism.
      SAMPLE: Dyslexic (n= 31) and non-dyslexic (n= 31) university students. METHOD:
      Questionnaire measures of self-rated confidence in writing, understanding of
      authorship, knowledge to avoid plagiarism, and top-down, bottom-up and pragmatic
      approaches to writing (Student Authorship Questionnaire; SAQ), and deep, surface
      and strategic approaches to learning (Approaches and Study Skills Inventory for
      Students; ASSIST), plus qualitative interviews with dyslexic students with high
      and low SAQ scores. RESULTS: Dyslexic students scored lower for confidence in
      writing, understanding authorship, and strategic approaches to learning, and
      higher for surface approaches to learning. Correlations among SAQ and ASSIST
      scores were larger and more frequently significant among non-dyslexic students.
      Self-rated knowledge to avoid plagiarism was associated with a top-down approach
      to writing among dyslexic students and with a bottom-up approach to writing among
      non-dyslexic students. All the dyslexic students interviewed described how
      dyslexia made writing more difficult and reduced their confidence in academic
      writing, but they had varying views about whether dyslexia increased the risk of
      plagiarism. CONCLUSIONS: Dyslexic students have less strong authorial identities,
      and less congruent approaches to learning and writing. Knowledge to avoid
      plagiarism may be more salient for dyslexic students, who may benefit from
      specific interventions to increase confidence in writing and understanding of
      authorship. Further research could investigate how dyslexic students develop
      approaches to academic writing, and how that could be affected by perceived
      knowledge to avoid plagiarism.

PMID- 22583093
TI  - Cognitive ability, academic achievement and academic self-concept: extending the
      internal/external frame of reference model.
AB  - BACKGROUND: Marsh's internal/external (I/E) frame of reference model depicts the
      relationship between achievement and self-concept in specific academic domains.
      Few efforts have been made to examine concurrent relationships among cognitive
      ability, achievement, and academic self-concept (ASC) within an I/E model
      framework. AIM: To simultaneously examine the influences of domain-specific
      cognitive ability and grades on domain self-concept in an extended I/E model,
      including the indirect effect of domain-specific cognitive ability on domain self
      concept via grades. SAMPLE: Tenth grade respondents (628 male, 452 female) to a
      national adolescent survey conducted in Taiwan. METHOD: Respondents completed
      surveys designed to measure maths and verbal aptitudes. Data on Maths and Chinese
      class grades and self-concepts were also collected. RESULTS: Statistically
      significant and positive path coefficients were found between cognitive ability
      and self-concept in the same domain (direct effect) and between these two
      constructs via grades (indirect effect). The cross-domain effects of either
      ability or grades on ASC were negatively significant. CONCLUSIONS: Taiwanese 10th
      graders tend to evaluate their ASCs based on a mix of ability and achievement,
      with achievement as a mediator exceeding ability as a predictor. In addition, the
      cross-domain effects suggest that Taiwanese students are likely to view Maths and
      verbal abilities and achievements as distinctly different.

PMID- 22583094
TI  - Is no praise good praise? Effects of positive feedback on children's and
      university students' responses to subsequent failures.
AB  - BACKGROUND: According to Dweck and colleagues, praise can be delivered using
      person ('you are clever') or process terms ('you worked hard'). Research suggests
      that giving people process praise after success can help them deal better with
      subsequent failures because it attributes outcomes to effort rather than fixed
      ability. However, research has thus far inadequately addressed how these types of
      praise compare to receiving no evaluative feedback. AIM: The aim of the present
      research was to examine the effects of person and process praise compared to a
      control group where only objective outcome feedback was given. SAMPLES: In Study
      1, 145 British school children aged 9-11 years took part. In Study 2,
      participants were 114 British university students. METHOD: In both studies,
      participants read three scenarios and were asked to imagine themselves as the
      main character. In each scenario, they succeeded in an educational task and
      received either person, process, or no praise. Participants then read two
      scenarios, where they failed at a task. Following each scenario participants
      evaluated their performance, affect, and persistence. RESULTS: After one failure,
      participants who received person praise reacted most negatively on all dependent
      measures. However, those in the process condition did not differ significantly
      from those in the control group. CONCLUSIONS: These findings suggest that process
      feedback may not be inherently positive; instead person feedback seems
      particularly detrimental.

PMID- 22583095
TI  - The effect of guiding questions on students' performance and attitude towards
      statistics.
AB  - BACKGROUND: In this study, the effect of guidance on students' performance was
      investigated. This effect was hypothesized to be manifested through a reduction
      of cognitive load and enhancement of self-explanations. AIM: The goal of this
      study was to investigate the effect of guiding questions on students'
      understanding of statistics. SAMPLE AND METHOD: In an experimental setting, two
      randomly selected groups of students (N= 49) answered achievement and transfer
      questions on statistics as a measure of performance. Students in the intervention
      condition were given guiding questions to direct their way of reasoning before
      they answered the achievement questions. The students in the control condition
      were asked to write down their way of thinking before they answered the same
      achievement questions. In this way, both groups were stimulated to self-explain,
      but only the reasoning processes of the students in the intervention condition
      were guided. RESULTS AND CONCLUSION: It was found that students in the
      intervention condition performed significantly better on achievement and transfer
      questions and that this effect of guidance was mediated by self-explanations.
      Attitude towards statistics was positively related to performance.

PMID- 22583097
TI  - Screening for plant health.

PMID- 22583096
TI  - The Teddy Bear Hospital in Australia.

PMID- 22583098
TI  - Arterial thromboembolism in senile systemic amyloidosis: report of two cases.
AB  - We describe a rare complication, systemic arterial thromboembolism, seen in two
      patients with senile systemic amyloidosis (SSA). Case 1 was a 73-year-old man who
      was tentatively diagnosed as having cardiac amyloidosis. Five months later, he
      was afflicted by severe left flank pain. CT disclosed renal infarction and then
      he received endomyocardial biopsy and the transthyretin (TTR) gene analysis,
      leading to the final diagnosis of SSA. Case 2 was an 88-year-old woman who had
      been definitively diagnosed as having SSA-related heart failure with atrial
      fibrillation two years before. She was transferred to the emergency room in our
      hospital and enhanced CT revealed complete occlusions of the left internal
      carotid and left vertebral arteries, both subclavian arteries, and the left renal
      and left internal iliac arteries. Paying much attention to intracardiac
      thrombosis might be necessary in taking care of SSA patients.

PMID- 22583099
TI  - Emphasis on autonomy and propensity for suicidal behavior in younger and older
      adults.
AB  - A cognitive style marked by emphasis on autonomy has been linked to negative
      outcomes throughout the life span. Two preliminary studies are presented that
      examined factors on a measure of autonomy (Personal Style Inventory-Revised) in
      relation to propensity for suicidal behavior (Suicidal Behaviors Questionnaire
      14; SBQ-14). Perfectionism, B=.15, SE=0.03, p<.01, and Defensive Separation,
      B=.04, SE=0.01, p <= .01, predicted SBQ-14 in younger adults. Need for Control,
      B=.234, SE=0.10, p<.05, predicted SBQ-14 in older adults. Findings suggest that
      aspects of autonomy may be relevant to understanding suicidal behavior; however,
      more research is needed examining the association between autonomy and suicidal
      behavior in the context of depression. Nonetheless, these studies suggest a
      promising avenue for future research.

PMID- 22583100
TI  - Quality parameters and RAPD-PCR differentiation of commercial baker's yeast and
      hybrid strains.
AB  - Baker's yeast, Saccharomyces cerevisiae, is a key component in bread baking.
      Total of 12 commercial baker's yeast and 2 hybrid strains were compared using
      traditional quality parameters. Total of 5 strains with high leavening power and
      the 2 hybrid strains were selected and evaluated for their alpha-amylase,
      maltase, glucoamylase enzymes, and compared using random amplified polymorphic
      DNA (RAPD). The results revealed that all selected yeast strains have a low level
      of alpha-amylase and a high level of maltase and glucoamylase enzymes. Meanwhile,
      the Egyptian yeast strain (EY) had the highest content of alpha-amylase and
      maltase enzymes followed by the hybrid YH strain. The EY and YH strains have the
      highest content of glucoamylase enzyme almost with the same level. The RAPD
      banding patterns showed a wide variation among commercial yeast and hybrid
      strains. The closely related Egyptian yeast strains (EY and AL) demonstrated
      close similarity of their genotypes. The 2 hybrid strains were clustered to
      Turkish and European strains in 1 group. The authors conclude that the
      identification of strains and hybrids using RAPD technique was useful in
      determining their genetic relationship. These results can be useful not only for
      the basic research, but also for the quality control in baking factories.

PMID- 22583101
TI  - How are curious people viewed and how do they behave in social situations? From
      the perspectives of self, friends, parents, and unacquainted observers.
AB  - OBJECTIVE: People who are open and curious orient their lives around an
      appreciation of novelty and a strong urge to explore, discover, and grow.
      Researchers have recently shown that being an open, curious person is linked to
      healthy social outcomes. METHOD: To better understand the benefits (and
      liabilities) of being a curious person, we used a multimethod design of social
      behavior to assess the perspectives of multiple informants (including self,
      friends, and parents) and behavior coded from direct observations in unstructured
      social interactions. RESULTS: We found an impressive degree of convergence among
      self, friend, and parent reports of curiosity, and observer-rated behavioral
      correlates of curiosity. A curious personality was linked to a wide range of
      adaptive behaviors, including tolerance of anxiety and uncertainty, positive
      emotional expressiveness, initiation of humor and playfulness, unconventional
      thinking, and a nondefensive, noncritical attitude. CONCLUSIONS: This
      characterization of curious people provides insights into mechanisms underlying
      associated healthy social outcomes.

PMID- 22583102
TI  - Cardiac surgery in patients with Fabry's disease: review of literature.
AB  - Fabry's disease is a rare but important cause of structural cardiac disease that
      may influence cardiac surgical decision making. Herein we present a case of
      mitral valve repair in a patient with Fabry's disease and review the cardiac
      related literature on this lysosomal storage disease.

PMID- 22583103
TI  - Evaluation of the H2)dedpa scaffold and its cRGDyK conjugates for labeling with
      64Cu.
AB  - Studies of the acyclic ligand scaffold H(2)dedpa and its derivatives with the
      peptide cRGDyK for application in copper radiopharmaceuticals are described.
      Previously shown to be a superb ligand for (67/68)Ga, the chelate is now shown to
      coordinate (64)Cu in its derivatized and nonderivatized forms rapidly under mild
      reaction conditions (10 min, RT, pH 5.5 10 mM sodium acetate buffered solution).
      The hexadentate, distorted octahedral coordination of H(2)dedpa is confirmed in
      the corresponding solid state X-ray crystal structure of [Cu(dedpa)]. Cyclic
      voltammetry determined the reduction potential of [Cu(dedpa)] to be below values
      found for common bioreductants. Reduction and reoxidation were irreversible but
      reproducible, indicating a potential change of coordination mode upon reduction
      of Cu(II) to Cu(I). The thermodynamic stability constant log K(CuL) was
      determined to be 19.16(5), comparable to other frequently used (64)Cu chelates.
      Serum stability of the (64)Cu labeled chelate revealed only 3%
      transchelation/association to serum proteins after 2 h, while the conjugates
      reveal 10% ([Cu(RGD1)]) and 6% ([Cu(RGD2)]) transchelation at the same time
      point.

PMID- 22583104
TI  - Isolation, fractionation and characterization of melanin-like pigments from
      chestnut (Castanea mollissima) shells.
AB  - Melanins are known as versatile biopolymers, but the utilizations are restricted
      by their poor solubilities. Therefore, well soluble ones or their analogs are
      much desired. In this article, a new procedure was developed for fractionation of
      the pigments isolated from chestnut (Castanea mollissima) shells, and 3 fractions
      (Fr. 1, Fr. 2, and Fr. 3) were obtained. The solubilities of all the fractions in
      waters of different pH and in common organic solvents were studied. The
      physicochemical properties of the fractions were characterized for the first time
      on the basis of combined chemical analyses and spectroscopic methods including
      ultraviolet-visible (UV-Vis), Fourier transform infrared (FT-IR), electron spin
      resonance (ESR), and solid-state 13C nuclear magnetic resonance (13C-NMR). All
      the fractions could be bleached by NaOCl and H2O2 and give a positive reaction
      for polyphenols, which are usually used as typical tests for allomelanins. Their
      UV-Vis, FT-IR, and ESR spectra resembled those of synthetic and some natural
      melanins. Elemental data and quantitative analyses of 13C-NMR spectra revealed
      that pigment-bound proteins and polysaccharides were the most abundant in Fr. 1,
      while Fr. 2 was presented with the highest aromaticity. PRACTICAL APPLICATION: We
      provided a new, simple, and inexpensive method to fractionate the melanin-like
      pigments from chestnut shells. This technique can be used to produce natural
      melanin-like food colorants with different solubilities from chestnut shells.

PMID- 22583105
TI  - Outcome of oral food challenges in children in relation to symptom-eliciting
      allergen dose and allergen-specific IgE.
AB  - BACKGROUND: Oral food challenge (FC) protocols are discussed with reference to
      starting doses, dose increments, safety, and predictability of results. The aim
      of this study was to evaluate the relation of eliciting allergen doses, specific
      IgE levels and predictive factors to the outcome of FCs in children. METHODS: In
      869 children (median age 1.2 years), FCs were performed with cow's milk (n =
      633), hen's egg (n = 456), wheat (n = 265) and/or soy (n = 317) starting at 3-5
      mg of protein. Each of the seven doses was administered every 30 min using semi
      log increases. Severity of symptoms was graded from I to V. IgE was determined
      prior to challenges. RESULTS: Of the children allergic to egg or milk, 9% and
      10%, respectively, experienced reactions already at the first dose. Of these, 14%
      (egg) and 4% (milk) experienced grade IV reactions. In contrast, few children
      reacted to the first doses of wheat or soy, and most reactions occurred after the
      maximum dose. For all allergens, grade V reactions did not occur. However, grade
      IV reactions were seen at all eliciting doses. Elevated specific IgE level, young
      age and a history of atopic dermatitis were associated with a positive challenge
      outcome for milk or egg, and also IgE levels were associated with lower eliciting
      allergen doses and more severe symptoms. CONCLUSION: Oral FCs bear a risk of
      severe reactions at all dose levels. Doses of 3-5 mg protein induced symptoms in
      up to 10% of children allergic to milk or egg. However, food-specific IgE levels
      are of limited clinical value for the estimation of FC reactions.

PMID- 22583106
TI  - Mutation of a cleavage site adjacent to the mature domain leads to increase in
      secreted mature BMP-2 with reduced activity.
AB  - Proteolytic cleavage of precursor bone morphogenetic protein (proBMP) is an
      important step in generating the active mature BMP. ProBMP-2 contains two
      proprotein convertase (PC) recognition sites (S1 and S2) and is postulated to be
      cleaved by PCs at those sites. Cell lines expressing proBMP-2, with a silenced S1
      site (mS1) that inhibited PC cleavage, secreted the 20-kDa form BMP-2, while
      cells expressing wild type (wt) BMP-2 secreted 18- and 20-kDa mature BMP-2 N
      terminal isoforms. The mS1 cells secreted 15-fold more mature BMP-2 than the wt,
      despite their similar mRNA levels. Mutant-secreted BMP-2 demonstrated biological
      activity in vitro; however, its activity was reduced compared with wt. These data
      demonstrate that proBMP-2 can be cleaved at an alternative cleavage site without
      prior S1 site cleavage in cell lines overexpressing BMP-2 and more importantly
      suggest that the presence of the 2-kDa linker peptide can affect activity and
      secretion of the mature protein.

PMID- 22583107
TI  - Ovarian remnant syndrome: comparison of laparotomy, laparoscopy and robotic
      surgery.
AB  - OBJECTIVE: To compare laparotomy, laparoscopy and robotic surgery in the
      management of ovarian remnant syndrome. DESIGN: Retrospective comparative study.
      SETTING: Mayo Clinic Arizona and Mayo Clinic Rochester, USA. POPULATION: Women
      who underwent surgical treatment for ovarian remnant syndrome. METHODS: The
      clinical records of 223 patients with histologically documented residual cortical
      ovarian tissue excised at Mayo Clinic by laparotomy, laparoscopy or a robotic
      approach, from January 1985 through February 2009, were reviewed. Data collected
      included the patient's age, body mass index, previous medical and surgical
      history, symptoms, prior management of ovarian remnant syndrome, preoperative
      imaging study, intraoperative details, postoperative course, complications and
      follow-up data. MAIN OUTCOME MEASURES: Intraoperative and postoperative outcomes.
      RESULTS: One hundred and eighty-seven patients (83.9%) were operated by
      laparotomy, 19 (8.5%) by laparoscopy and 17 (7.6%) by a robotic approach.
      Estimated blood loss and length of stay were significantly lower in the robotic
      and laparoscopic groups compared with laparotomy (p < 0.01). After a mean follow
      up of 21.1 +/- 32.4 months, the rate of pain improvement was 93.1, 94.4 and 71.4%
      for the laparotomy, laparoscopy and robotic surgery group, respectively.
      CONCLUSIONS: Robotic and laparoscopic surgery for the treatment of ovarian
      remnant syndrome offer advantages over laparotomy in terms of reduced blood loss,
      lower postoperative complications and shorter length of stay.

PMID- 22583108
TI  - Cryoprecipitate for transfusion: which patients receive it and why? A study of
      patterns of use across three regions in England.
AB  - BACKGROUND: Despite increasing interest in the use of fibrinogen concentrates,
      cryoprecipitate remains the major source of fibrinogen in England. OBJECTIVES:
      Understand patterns and indications for use of cryoprecipitate in hospitals from
      three English regions. METHOD/MATERIALS: Data collection over 3 months from
      adults, children and neonates receiving cryoprecipitate, including clinical
      scenario, indications, dose and levels of fibrinogen concentrations pre- and post
      transfusion. RESULTS: Four hundred and twenty-three episodes of cryoprecipitate
      transfusion were analysed from 39 hospitals. Use varied from 0.1 to 4.9 units per
      100 red cells transfused. The primary indication was haemorrhage [311 episodes
      (74%)]. The commonest clinical scenario in all age groups was cardiac surgery,
      followed by trauma in adults and critical/neonatal care for children. Pre
      treatment fibrinogen levels were measured in 322 episodes. In 179 episodes, the
      level was >= 1.0 g L(-1) . CONCLUSION: Wide variation in practice and dose
      suggests inconsistent practice and uncertainty in the evidence informing optimal
      use of cryoprecipitate.

PMID- 22583109
TI  - Improved outlook on HIV-1 prevention and vaccine development.
AB  - INTRODUCTION: The development of an effective vaccine against HIV-1 has been
      challenging but recent advances in both the HIV prevention landscape and the
      partial efficacy of the recent RV144 vaccine efficacy trial in Thailand provide
      hope for an improved arsenal of approaches to prevent HIV-1 transmission. AREAS
      COVERED: This review describes recent advances in HIV-1 prevention such as
      circumcision, microbicides and pre-exposure prophylaxis with antiretroviral
      therapy, but focuses mainly on the current state of HIV-1 vaccine development in
      the post-RV144 era. EXPERT OPINION: The field of HIV-1 vaccine development has
      been plagued by the unprecedented challenges involved with designing a vaccine
      effective in preventing transmission of a retrovirus, due in part to sequence
      diversity, retroviral integration into host chromosomes, establishment of
      reservoir sites and glycosylation shielding of the HIV-1 envelope. The partial
      efficacy of the recent RV144 vaccine trial in Thailand may allow for better
      understanding of immune correlates of infection risk, which could enable
      iterative improvements to vaccine regimens in the development pipeline. In
      parallel, a number of promising vaccine strategies incorporating viral vectors,
      novel immunogens, delivery systems and adjuvants are advancing in clinical
      development. Vaccine development must occur in parallel with continued advances
      in HIV-1 prevention.

PMID- 22583110
TI  - Preoperative stenting for ureteroscopic lithotripsy for a large renal stone.
AB  - A large renal stone can be treated ureteroscopically, but the treatment often
      requires more than one procedure. The use of stenting before ureteroscopy was
      recently reported. The present study investigated the effectiveness of
      preoperative stenting before ureteroscopic lithotripsy for large (>15 mm) renal
      stones. A ureteral stent was intentionally inserted in 25 patients undergoing
      ureteroscopic surgery. A group of 36 non-prestented patients was used as control.
      Median stone diameter was 21 mm in both groups. Pre-ureteroscopy stenting
      significantly improved the stone-free rate, defined as stones <2 mm and <4 mm (P
      < 0.05), whereas it did not significantly improve the stone-free rate defined as
      0 mm (P = 0.12). The uretereoscopy success rate was 72.0% in the stented and
      55.6% in the control group (P = 0.09). A 14/16-Fr ureteral access sheath was
      successfully inserted in 94.7% of the stented patients, and 74.2% of the non
      stented patients (P < 0.05). Our findings showed that preoperative stenting is
      effective for dilation of the ureter, and also to facilitate the insertion of a
      ureteral access sheath in patients undergoing ureteroscopic lithotripsy for large
      renal stones.

PMID- 22583111
TI  - Design of an interactive digital nutritional education package for elderly
      people.
AB  - Designing a system for the elderly is crucial, as aging is associated with
      physiological changes that may impair perception, cognition and other social
      aspects; therefore, many aspects need consideration, especially in interface
      design. This study was conducted to develop a digital nutritional education
      package (WE Sihat) by following appropriate guidelines for elderly people to
      achieve better design interface and interaction. Touch-screen technology was used
      as a platform for user interaction. The nutritional content was based on previous
      nutrition studies and a lifestyle education package on healthy aging, which
      contains four modules. The questionnaires were distributed to 31 Malay subjects
      aged 60-76 years old, containing an evaluation about the overall content,
      graphics, design layout, colour, font size, audio/video, user-perceived
      satisfaction and acceptance levels. The findings showed positive feedback and
      acceptance. Most subjects agreed that the digital nutritional education package
      can increase their nutritional knowledge for a healthy lifestyle and is easy to
      use. The touch-screen technology was also well accepted by elderly people and can
      be used as a kiosk for disseminating nutrition education for healthy aging.

PMID- 22583112
TI  - Asymmetric pericyclic cascade approach to spirocyclic oxindoles.
AB  - The reaction of chiral N-arylnitrones with carbocyclic alkylarylketenes generates
      spirocyclic oxindoles in good yields and with excellent levels of
      enantioselectivity (90-99% ee) via a pericyclic cascade process.

PMID- 22583113
TI  - The package approach to growing peanuts.

PMID- 22583115
TI  - Scalable, divergent synthesis of meroterpenoids via "borono-sclareolide".
AB  - A scalable, divergent synthesis of bioactive meroterpenoids has been developed. A
      key component of this work is the invention of "borono-sclareolide", a terpenyl
      radical precursor that enables gram-scale preparation of (+)-chromazonarol.
      Subsequent synthetic operations on this key intermediate permit rapid access to a
      variety of related meroterpenoids, many of which possess important biological
      activity.

PMID- 22583114
TI  - Validation of interobserver agreement in lung cancer assessment: hematoxylin
      eosin diagnostic reproducibility for non-small cell lung cancer: the 2004 World
      Health Organization classification and therapeutically relevant subsets.
AB  - CONTEXT: Precise subtype diagnosis of non-small cell lung carcinoma is
      increasingly relevant, based on the availability of subtype-specific therapies,
      such as bevacizumab and pemetrexed, and based on the subtype-specific prevalence
      of activating epidermal growth factor receptor mutations. OBJECTIVES: To
      establish a baseline measure of interobserver reproducibility for non-small cell
      lung carcinoma diagnoses with hematoxylin-eosin for the current 2004 World Health
      Organization classification, to estimate interobserver reproducibility for the
      therapeutically relevant squamous/nonsquamous subsets, and to examine
      characteristics that improve interobserver reproducibility. DESIGN: Primary,
      resected lung cancer specimens were converted to digital (virtual) slides. Based
      on a single hematoxylin-eosin virtual slide, pathologists were asked to assign a
      diagnosis using the 2004 World Health Organization classification. Kappa
      statistics were calculated for each pathologist-pair for each slide and were
      summarized by classification scheme, pulmonary pathology expertise, diagnostic
      confidence, and neoplastic grade. RESULTS: The 12 pulmonary pathology experts and
      the 12 community pathologists each independently diagnosed 48 to 96 single
      hematoxylin-eosin digital slides derived from 96 cases of non-small cell lung
      carcinoma resection. Overall agreement improved with simplification from the
      comprehensive 44 World Health Organization diagnoses (kappa  =  0.25) to their 10
      major header subtypes (kappa  =  0.48) and improved again with simplification
      into the therapeutically relevant squamous/nonsquamous dichotomy (kappa  = 
      0.55). Multivariate analysis showed that higher diagnostic agreement was
      associated with better differentiation, better slide quality, higher diagnostic
      confidence, similar years of pathology experience, and pulmonary pathology
      expertise. CONCLUSIONS: These data define the baseline diagnostic agreement for
      hematoxylin-eosin diagnosis of non-small cell lung carcinoma, allowing future
      studies to test for improved diagnostic agreement with reflex ancillary tests.

PMID- 22583116
TI  - A delayed presentation of congenital glaucoma.

PMID- 22583118
TI  - Doctor-patient communication and cancer patients' choice of alternative therapies
      as supplement or alternative to conventional care.
AB  - Cancer patients' use of complementary and alternative medicine (CAM) is
      widespread, despite the fact that clinical studies validating the efficacy of CAM
      remain sparse in the Nordic countries. The purpose of this study was to explore
      possible connections between cancer patients' communication experiences with
      doctors and the decision to use CAM as either supplement or alternative to
      conventional treatment (CT). The Regional Committee for Medical and Health
      Research Ethics and the Norwegian Data Inspectorate approved the study. From a
      group of 52 cancer patients with self-reported positive experiences from use of
      CAM, 13 were selected for qualitative interviews. Six used CAM as supplement, and
      seven as alternative to CT, periodically or permanently. Communication
      experiences with 46 doctors were described. The analysis revealed three
      connections between doctor-patient communication and patients' treatment
      decisions: (i) negative communication experiences because of the use of CAM; (ii)
      negative communication experiences resulted in the decision to use CAM, and in
      some cases to decline CT; and (iii) positive communication experiences led to the
      decision to use CAM as supplement, not alternative to CT. The patients, including
      the decliners of CT, wanted to discuss treatment decisions in well-functioning
      interpersonal processes with supportive doctors. In doctors' practices and
      education of doctors, a greater awareness of potential positive and negative
      outcomes of doctor-patient communication that concern CAM issues could be of
      importance. More research is needed to safeguard CAM users' treatment decisions
      and their relationship to conventional health care.

PMID- 22583117
TI  - Macrophages and mesenchymal stromal cells support survival and proliferation of
      multiple myeloma cells.
AB  - Multiple myeloma (MM) is characterized by almost exclusive tropism of malignant
      cells for the bone marrow (BM) milieu. The survival and proliferation of
      malignant plasma cells have been shown to rely on interactions with nonmalignant
      stromal cells, in particular mesenchymal stromal cells (MSCs), in the BM
      microenvironment. However, the BM microenvironment is composed of a diverse array
      of cell types. This study examined the role of macrophages, an abundant component
      of BM stroma, as a potential niche component that supports malignant plasma
      cells. We investigated the proliferation of MM tumour cell lines when cultured
      alone or together with MSCs, macrophages, or a combination of MSCs and
      macrophages, using the carboxyfluorescein succinimidyl ester assay. Consistently,
      we observed increased proliferation of MM cell lines in the presence of either
      MSCs or macrophages compared to cell line-only control. Furthermore, the combined
      co-culture of MSCs plus macrophages induced the greatest degree of proliferation
      of myeloma cells. In addition to increased proliferation, MSCs and macrophages
      decreased the rate of apoptosis of myeloma cells. Our in vitro studies provide
      evidence that highlights the role of macrophages as a key component of the BM
      microenvironment facilitating the growth of malignant plasma cells in MM.

PMID- 22583119
TI  - Changes in selected physical property and enzyme activity of rice and barley koji
      during fermentation and storage.
AB  - Koji are solid-state fermentation products made by inoculating steamed grains
      with the spores of fungi, particularly Aspergillus spp. This research was
      undertaken to identify the fermentation and storage conditions optimal for the
      production and maintenance of selected hydrolytic enzymes, such as alpha-amlyase
      and protease, in koji. Steamed rice and barley were inoculated with 2 * 10 11
      Aspergillus oryzae spores per kilogram of grains and fermented for 118 h in a
      growth chamber at 28 to 32  degrees C with controlled relative humidities.
      Samples were drawn periodically during fermentation and storage at -20, 4, or 32 
      degrees C, and alpha-amylase and protease activity, mold counts, a(w), moisture
      contents, and pH of collected samples were determined. It was observed that the
      a(w), moisture contents, and pH of the koji were influenced by the duration of
      fermentation and temperature of storage. The alpha-amylase activity of both koji
      increased as the populations of A. oryzae increased during the exponential growth
      phase. The enzyme activity of barley koji was significantly higher than that of
      rice koji, reaching a peak activity of 211.87 or 116.57 U at 46 and 58 h,
      respectively, into the fermentation process. The enzyme activity in both products
      started to decrease once the mold culture entered the stationary growth phase.
      The protease activities of both koji were low and remained relatively stable
      during fermentation and storage. These results suggest that rice and barley koji
      can be used as sources of alpha-amylase and desired enzyme activity can be
      achieved by controlling the fermentation and storage conditions. PRACTICAL
      APPLICATION: Amylases and proteases are 2 important hydrolytic enzymes. In the
      food industry, these enzymes are used to break down starches and proteins while
      reducing the viscosity of foods. Although amylases and proteases are found in
      plants and animals, commercial enzymes are often produced using bacteria or molds
      through solid state fermentation, which is designed to use natural microbial
      process to produce enzymes in a controlled environment. A properly produced and
      maintained koji with a high hydrolytic enzyme activity can serve as an important
      source of the enzymes for the food industry.

PMID- 22583120
TI  - Efficacy of fibrinogen/thrombin-coated equine collagen patch in controlling
      lymphatic leaks.
AB  - We report the use of fibrinogen/thrombin-coated equine collagen patch
      (Tachosil((r)) ) as a sealant agent in six patients who underwent heart surgery
      for congenital heart disease (CHD) and developed an intraoperative lymphatic
      leakage detected at the time of surgery. The use of fibrinogen/thrombin-coated
      equine collagen patch proved to be safe and effective in preventing the
      development of postoperative chylothorax.

PMID- 22583121
TI  - Arabidopsis thaliana root growth kinetics and lunisolar tidal acceleration.
AB  - * All living organisms on Earth are continually exposed to diurnal variations in
      the gravitational tidal force due to the Sun and Moon. * Elongation of primary
      roots of Arabidopsis thaliana seedlings maintained at a constant temperature was
      monitored for periods of up to 14 d using high temporal- and spatial-resolution
      video imaging. The time-course of the half-hourly elongation rates exhibited an
      oscillation which was maintained when the roots were placed in the free-running
      condition of continuous illumination. * Correlation between the root growth
      kinetics collected from seedlings initially raised under several light protocols
      but whose roots were subsequently in the free-running condition and the lunisolar
      tidal profiles enabled us to identify that the latter is the probable exogenous
      determinant of the rhythmic variation in root elongation rate. Similar
      observations and correlations using roots of Arabidopsis starch mutants suggest a
      central function of starch metabolism in the response to the lunisolar tide. The
      periodicity of the lunisolar tidal signal and the concomitant adjustments in root
      growth rate indicate that an exogenous timer exists for the modulation of root
      growth and development. * We propose that, in addition to the sensitivity to
      Earthly 1G gravity, which is inherent to all animals and plants, there is another
      type of responsiveness which is attuned to the natural diurnal variations of the
      lunisolar tidal force.

PMID- 22583122
TI  - A tripodal ruthenium-gadolinium metallostar as a potential alpha(v)beta(3)
      integrin specific bimodal imaging contrast agent.
AB  - Gd(III)-containing metallostar contrast agents are gaining increased attention,
      because their architecture allows for a slower tumbling rate, which, in turn,
      results in larger relaxivities. So far, these metallostars find possible
      applications as blood pool contrast agents. In this work, the first example of a
      tissue-selective metallostar contrast agent is described. This RGD-peptide
      decorated Ru(II)(Gd(III))(3)metallostar is synthesized as an alpha(v)beta(3)
      integrin specific contrast agent, with possible applications in the detection of
      atherosclerotic plaques and tumor angiogenesis. The contrast agent showed a
      relaxivity of 9.65 s(-1) mM(-1), which represents an increase of 170%, compared
      to a low-molecular-weight analogue, because of a decreased tumbling rate (tau(R)
      = 470 ps). The presence of the MLCT band (absorption 375-500 nm, emission 525-850
      nm) of the central Ru(II)(Ph-Phen)(3)-based complex grants the metallostar
      attractive luminescent properties. The (3)MLCT emission is characterized by a
      quantum yield of 4.69% and a lifetime of 804 ns, which makes it an interesting
      candidate for time-gated luminescence imaging. The potential application as a
      selective MRI contrast agent for alpha(v)beta(3)-integrin expressing tissues is
      shown by an in vitro relaxometric analysis, as well as an in vitroT(1)-weighted
      MR image.

PMID- 22583123
TI  - Association of TCF7L2 and ADIPOQ with body mass index, waist-hip ratio, and
      systolic blood pressure in an endogamous ethnic group of India.
AB  - Despite the increasing burden of type 2 diabetes (T2D) and its established
      association with anthropometric and physiological traits as a risk factor,
      genetic studies focusing on the association of T2D-related genes with
      quantitative traits like body mass index (BMI), waist-hip ratio (WHR), and
      systolic blood pressure (SBP) are only a few for western populations and rare for
      Indian populations. The present study tested the association of TCF7L2, HHEX,
      KCNJ11, and ADIPOQ with BMI, SBP, and WHR in men and women of the Aggarwal
      population of India and found a differential association of TCF7L2 (rs7903146,
      rs4506565, and rs12256372) and ADIPOQ (rs2241766 and rs1501299) genes with
      increasing BMI, SBP, and WHR between the two sexes. We conclude that TCF7L2 and
      ADIPOQ together might play an important role in explaining these traits and to
      understand the biological and genetic mechanisms underlying T2D, and the role of
      other T2D genes must also be evaluated with these continuous traits.

PMID- 22583124
TI  - Recognition of early myocardial infarction by immunohistochemical staining with
      cardiac troponin-I and complement C9.
AB  - The diagnosis of early myocardial infarction (MI) after death, especially in the
      first few hours (c. 6 h) after the onset of MI, poses a challenge to the forensic
      pathologists. During this time, the damaged myocardium does not show grossly
      identifiable morphological changes and may not be recognized even with routine
      histological microscopic examination. However, the infarcted cardiac tissue
      releases certain chemicals that can be detected microscopically, two of these
      being cardiac troponin-I (CT-I) and complement C9 (C9). This study utilizes the
      importance of these two biomarkers immunohistochemically in an attempt to
      identify this early phase of MI. This study reveals that the early phase of MI of
      <6 h duration may be detected through immunohistochemical staining with CT-I and
      C9. The ischemic/infarcted cardiac myofibers in the <6 h group display
      reduced/absent CT-I staining as well as positive C9 staining.

PMID- 22583125
TI  - Does antenatal physical therapy for pregnant women with low back pain or pelvic
      pain improve functional outcomes? A systematic review.
AB  - OBJECTIVE: A systematic review was undertaken to update the understanding of the
      available evidence for antenatal physical therapy interventions for low back or
      pelvic pain in pregnant women to improve functional outcomes when compared with
      other treatments or no treatment. DATA SOURCES: Seven electronic databases were
      systematically searched and supplemented by hand searching through reference
      lists. METHODS OF STUDY SELECTION: Two reviewers independently selected trials
      for inclusion and independently assessed the internal validity of the included
      trials using the Clinical Appraisal Skills Program tool. RESULTS: Four trials
      with 566 participants were identified that met the inclusion criteria. The
      validity of the trials was moderate. Exercise, pelvic support garments and
      acupuncture were found to improve functional outcomes in pregnant women with low
      back or pelvic pain. No meta-analysis was performed because of the heterogeneity
      of functional outcome measures. CONCLUSIONS: While there is some evidence that
      physical therapy using exercise, acupuncture and pelvic supports may be useful,
      further research needs to consider other treatment modalities used by physical
      therapists and establish an appropriate, reliable and valid functional outcome
      measure to assess low back and pelvic pain in pregnancy.

PMID- 22583126
TI  - Efficient synthesis of gamma-keto sulfones by NHC-catalyzed intermolecular
      Stetter reaction.
AB  - The N-heterocyclic carbene-catalyzed intermolecular Stetter reaction of aldehydes
      with alpha,beta-unsaturated sulfones allows the atom-economic and selective
      formation of gamma-keto sulfones in good yields. Key to the success of this
      unique transition-metal-free carbon-carbon bond-forming reaction is the right
      choice of the NHC precursor and base. The reaction tolerates a broad range of
      different aldehydes.

PMID- 22583127
TI  - Biosimilar insulins.
AB  - Until now most insulin used in developed countries is manufactured and
      distributed by a small number of multinational companies. Other pharmaceutical
      companies - many of these are located in countries such as India or China - are
      also able to manufacture insulin with modern biotechnological methods.
      Additionally, the patents for many insulin formulations have expired or are going
      to expire soon. This enables such companies to produce insulins and to apply for
      market approval of these as biosimilar insulins (BIs) in highly regulated markets
      such as the EU or the US. To understand the complexity of BIs' approval and
      usage, scientific and regulatory aspects have to be discussed. Differences in the
      manufacturing process (none of the insulin-manufacturing procedures are
      identical) result in the fact that all insulin that might become BIs differ from
      the originator insulin to some extent. The question is, have such differences in
      the structure of the insulin molecule and or the purity and so on clinically
      relevant consequences for the biological effects induced or not. The guidelines
      already in place in the EU for market approval require that the manufacturer
      demonstrates that his insulin has a safety and efficacy profile that is similar
      to that of the 'original' insulin formulation. Recently guidelines for
      biosimilars were issued in the US; however, these do not cover insulin. Although
      a challenging approval process for insulins to become BI might be regarded as a
      hurdle to keep companies out of certain markets, it is fair to say that the
      potential safety and efficacy issues surrounding BI are substantial and relevant,
      and do warrant a careful and evidence-driven approval process. Nevertheless, it
      is very likely that in the next years, BIs will come to the market also in highly
      regulated markets.

PMID- 22583128
TI  - Design and characterisation of doxorubicin-releasing chitosan microspheres for
      anti-cancer chemoembolisation.
AB  - The aims of this study were to design and characterise doxorubicin-loaded
      chitosan microspheres for anti-cancer chemoembolisation. Doxorubicin-loaded
      chitosan microspheres were prepared by emulsification and cross-linking methods.
      Doxorubicin-chitosan solution was initially complexed with tripolyphosphate (TPP)
      to improve drug loading capabilities. Doxorubicin-loaded chitosan microspheres
      were highly spherical and had approximately diameters of 130-160 um in size. Drug
      loading amount and loading efficiency were in the range 3.7-4.0% and 68.5-85.8%,
      respectively, and affected by TPP concentration, drug levels and cross-linking
      time. Doxorubicin release was affected by TPP complexation, cross-linking time
      and release medium. Especially, lysozyme in release media considerably increased
      drug release. Synergistic anti-cancer activities of doxorubicin-releasing
      chitosan microspheres were confirmed to VX2 cells in the rabbit auricle model
      compared with blank microspheres. Doxorubicin-loaded chitosan microspheres can
      efficiently be prepared by TPP gelation and cross-linking method and developed as
      multifunctional anti-cancer embolic material.

PMID- 22583129
TI  - Topical delivery of retinol emulsions co-stabilised by PEO-PCL-PEO triblock
      copolymers: effect of PCL block length.
AB  - This article describes enhanced skin permeation and UV/thermal stability of
      retinol emulsions by the co-stabilisation of Tween20 and biodegradable
      poly(ethylene oxide)-block-poly(epsilon-caprolactone)-block-poly(ethylene oxide)
      (PEO-PCL-PEO) triblock copolymers having different lengths of hydrophobic PCL
      block. A triblock copolymer with a longer PCL block has a lower hydrophile
      lipophile balance (HLB) value. Commercial Retinol 50C(r) (BASF Co., Ludwigshafen,
      Germany) was used as the source of retinol. Ultrasonication of the Retinol 50C(r)
      emulsion with the triblock copolymers led to an increase in retinol
      solubilisation and a decrease in average particle size of the resulting retinol
      emulsion. These characteristics improved skin permeation of retinol through the
      stratum corneum of artificial skin and subsequent proliferation of viable
      epidermis cell. Employment of the triblock copolymer with a longer PCL block
      increased both UV and thermal stabilization of the retinol. These results suggest
      that HLB and PCL block length are important factors to enhance the topical
      delivery of retinol into the skin.

PMID- 22583130
TI  - Adverse effects of the anabolic steroid, boldenone undecylenate, on reproductive
      functions of male rabbits.
AB  - This study was conducted to evaluate the adverse effects of the anabolic steroid,
      boldenone undecylenate (BOL) on reproductive functions of male rabbits. Thirty
      white New Zealand mature male rabbits were divided into three groups (10 rabbits
      each). Group A rabbits served as a control group. Group B rabbits received 4.4
      mg/kg body weight (bwt) BOL 5% oily solution. Group C rabbits received 8.8 mg/kg
      bwt BOL. Rabbits were injected intramuscularly twice weekly for two months. BOL
      had no significant effect on the bwt and bwt gain. Testes and epididymis weights
      were decreased significantly in the BOL-treated groups. BOL caused significant
      reduction in serum testosterone level, seminal volume, sperm motility, and sperm
      count. No abnormalities were detected in the sperm morphology of the BOL-treated
      groups. Histopathological alterations in the testes and epididymis were marked in
      the group C rabbits. These results indicate that administration of BOL exerts a
      significant harmful effect on the reproductive functions of male rabbits.

PMID- 22583131
TI  - Oestrogen-deficiency inducing haematopoiesis dysfunction via reduction in
      haematopoietic stem cells and haematopoietic growth factors in rats.
AB  - Haematopoiesis is a self-renewing and multi-directional differentiation process
      of haematopoietic stem cells (HSCs), which is modulated very precisely by the
      haematopoietic microenvironment in bone marrow. Our previous study has
      demonstrated that oestrogen-deficiency leads to haematopoiesis dysfunction which
      manifests as a decrease in haematopoietic tissues and an increase in adipose
      tissues in bone marrow. However, the mechanism involved in the oestrogen
      deficiency effects on haematopoiesis dysfunction is not completely understood. In
      this study, we established an oestrogen-deficiency rat model by ovariectomy (OVX
      group). Haematopoiesis was evaluated at the 12th, 16th, 20th, 24th and 28th weeks
      after operation in the OVX group and its control (Sham group) by pathological
      examination; the number and function of HSCs were evaluated by flow cytometry
      analysis and colony-forming assay respectively. Haematopoietic growth factors
      levels including granulocyte/macrophage-colony-stimulating factor (GM-CSF), stem
      cell factor (SCF) and interleukin-3 (IL-3) were examined by ELISA kits at
      different time points. We found that in the OVX group, haematopoiesis dysfunction
      in bone marrow was observed (P < 0.05) from the 12th week when compared with the
      Sham group, and extramedullary haematopoiesis began to appear in the liver and
      spleen from the 16th week. The number of HSCs and colony-forming units
      granulocyte/macrophage (CFUs-GM) in bone marrow was reduced significantly (P <
      0.05) from the 20th and 16th week respectively. Furthermore, GM-CSF, SCF and IL-3
      in the OVX group decreased significantly (P < 0.05) since the 12th, 16th and 24th
      week respectively. Taken together, these results suggested that oestrogen is
      required for normal haematopoiesis. Oestrogen-deficiency inducing haematopoiesis
      dysfunction may be via reduction in HSCs and haematopoietic growth factors at a
      late stage.

PMID- 22583132
TI  - Reduction of insulin signalling pathway IRS-1/IRS-2/AKT/mTOR and decrease of
      epithelial cell proliferation in the prostate of glucocorticoid-treated rats.
AB  - Previous studies by our research group using a model of insulin resistance
      induced by dexamethasone (DEX) showed that in the rat ventral prostate there was
      epithelial and smooth muscle cell atrophy and there were also alterations in
      fibroblasts. Proteins of the insulin signalling pathway are known to be very
      important for cell proliferation and development. Thus, we investigated the
      insulin signalling pathway and epithelial proliferation in the rat ventral
      prostate in this model and correlated the findings with expression of
      glucocorticoid (GR) and androgen (AR) receptors. Insulin resistance was induced
      in adult male Wistar rats by injection of DEX (1 mg/kg, ip for 5 consecutive
      days), whereas control (CTL) rats received saline. DEX treatment resulted in a
      significant decrease in body weight, but not in prostate weight. Reductions in
      insulin receptor 1 (IRS-1) (CTL 1.11 +/- 0.06; DEX 0.85 +/- 0.03), IRS-2 (CTL
      0.95 +/- 0.05; DEX 0.49 +/- 0.04), AKT (CTL 0.98 +/- 0.03; DEX 0.78 +/- 0.02),
      mammalian target of rapamycin (mTOR; CTL 0.65 +/- 0.08; DEX 0.22 +/- 0.05), GR
      (CTL 1.30 +/- 0.09; DEX 0.57 +/- 0.10) and AR (CTL 1.83 +/- 0.16; DEX 0.55 +/-
      0.08) protein levels were observed in the prostate of DEX-treated rats. The
      expression of the IRalpha-subunit, phosphoinositide 3-kinase, p-AKT, p70(S6K) ,
      extracellular signal-regulated kinase (ERK) and p-ERK was not altered. The
      frequency of AR-positive cells in the epithelium of the prostate decreased in the
      glucocorticoid-treated group, and the intensity of the reaction for this receptor
      in the cell nuclei was lower in this group. Furthermore, the treatment with DEX
      reduced the frequency of proliferating cell nuclear antigen-positive (PCNA) cells
      30-fold. This study suggests that the reduction in the insulin signalling pathway
      proteins IRS-1/IRS-2/AKT/mTOR in the prostate of DEX-treated rats may be
      associated with the morphological alterations observed previously.

PMID- 22583133
TI  - Effects of long-term experimental diabetes on adrenal gland growth and
      phosphoribosyl pyrophosphate formation in growth hormone-deficient dwarf rats.
AB  - The availability of growth hormone (GH)-deficient dwarf rats with otherwise
      normal pituitary function provides a powerful tool to examine the relative role
      of hyperglycaemia and the reordering of hormonal factors in the hypertrophy
      hyperfunction of the adrenal gland that is seen in experimental diabetes. Here,
      we examine the effects of long-term (6 months) experimental diabetes on the
      growth of the adrenal glands; their content of phosphoribosyl pyrophosphate
      (PRPP); and the activity of the PRPP synthetase, G6P dehydrogenase and 6PG
      dehydrogenase enzymes in GH-deficient dwarf rats compared to heterozygous
      controls. These parameters were selected in view of the known role of PRPP in
      both de novo and salvage pathways of purine and pyrimidine synthesis and in the
      formation of NAD, and in view of the role of the oxidative enzymes of the pentose
      phosphate pathway in both R5P formation and the generation of the NADPH that is
      required in reductive synthetic reactions. This study shows that GH deficiency
      prevents the increase in adrenal gland weight, PRPP synthetase, PRPP content and
      G6P dehydrogenase and 6PG dehydrogenase. This contrasts sharply with the
      heterozygous group that showed the expected increase in these parameters. The
      blood glucose levels of the groups of long-term diabetic rats, both GH-deficient
      and heterozygous, remained at an elevated level throughout the experiment. These
      results are fully in accord with earlier evidence from studies with somatostatin
      analogues which showed that the GH-insulin-like growth factor I (IGF-I)-axis
      plays a key role in the adrenal diabetic hypertrophy-hyperfunction syndrome.

PMID- 22583134
TI  - Reovirus type-2 infection in newborn DBA/1J mice reduces the development of late
      allergic asthma.
AB  - The aim of the present study was to determine whether or not the development of a
      helper T (Th) 1 response induced by Reovirus type-2 (Reo-2) infection would
      protect against the development of Th2-mediated late allergic asthma. This
      hypothesis was examined by infecting one day old neonatal DB A/1J mice with Reo-2
      in an ovalbumin (OVA)-induced late asthma model. Compared with the controls
      (either infected or uninfected mice with or without OVA sensitization and/or OVA
      challenge), Reo-2 infection lessened the magnitude of the subsequent allergic Th2
      mediated late asthma. In infected mice with allergic late asthma, there was
      decreased infiltration of interleukin (IL)-4(+), IL-5(+), IL-13(+) and very late
      antigen (VLA)-4(+) lymphocytes, and eotaxin-2(+) and VLA-4(+) eosinophils, in
      both bronchial and bronchiolar lesions. Also the expression of vascular cell
      adhesion molecule (VCAM)-1 and eotaxin-2 on vascular endothelial cells was
      reduced. Moreover, the systemic production of IL-4, IL-5, tumour necrosis factor
      alpha and OVA-specific IgE was reduced, whereas systemic IFN-gamma production was
      increased. In addition, there was no increase in IFN-alpha production. Thus the
      present study suggests that systemic Reo-2 infection at birth may reduce the
      development of subsequent late allergic asthma by the induction of a Th1
      response. Therefore the potential suppressive mechanism(s) that might be induced
      by Reo-2 infection in newborn mice and their effects on the development of late
      allergic asthma are discussed.

PMID- 22583135
TI  - Diagnostic evaluation of patients with nonimmediate cutaneous hypersensitivity
      reactions to iodinated contrast media.
AB  - BACKGROUND: Nonimmediate hypersensitivity reactions to iodinated contrast media
      (CM) are common. Allergological evaluation is necessary to confirm the diagnosis
      and to find a tolerated alternative. The aim of this study was to establish the
      role of skin testing and the drug provocation test (DPT) in the diagnosis of
      nonimmediate reactions to CM. METHODS: Skin intradermal testing and patch testing
      with delayed readings were carried out with different CM (iobitridol, iomeprol,
      iodixanol, iohexol, ioversol, iopramide and ioxaglate). Single-blind placebo
      controlled DPT was carried out in those cases with a negative skin test. In seven
      cases, a skin biopsy was obtained from positive skin tests and positive DPT.
      RESULTS: Of the 161 subjects evaluated, 34 (21.1%) were skin-test positive, 21
      (50%) to Iomeprol, 7 (16.7%) to Iodixanol, 5 (11.9%) to Iobitridol, 4 (9.5%) to
      Ioxaglate, 3 (7.1%) to Iohexol and 1 (2.4%) to Iopramide. DPT was positive in 44
      cases (34.6%) that were skin-test negative, 38 (76%) to Iodixanol, 8 (16%) to
      Iomeprol and 4 (8%) to Iohexol. Of 78 cases (48.4%) with confirmed
      hypersensitivity, 34 (43.6%) were identified by skin testing and 44 (56.4%) by
      DPT. Skin biopsies showed a perivascular mononuclear cell infiltrate, mainly in
      the dermis, with higher levels of CD4 than CD8 T lymphocytes, with expression of
      activation markers and skin homing receptors. CONCLUSION: Patients with
      nonimmediate reactions to CM were identified by skin testing in 43.6% and by DPT
      in 56.4%. The method to confirm the diagnosis differed depending on the CM
      involved.

PMID- 22583136
TI  - Longitudinal assessment of distress and quality of life in the early stages of
      breast cancer treatment.
AB  - BACKGROUND: During breast cancer treatment, a decline in quality of life and the
      patient's psychological well-being is observed. The purpose of this study was to
      assess levels of quality of life and psychological distress during breast cancer
      treatment. METHODS: Utilizing a longitudinal design, patients with breast cancer
      were assessed at three time-points during treatment. The within-subject analysis
      of variance was conducted to compare subscales of quality of life. Linear
      regression analyses were utilized to determine the contribution of psychological
      distress to the quality of life at each time assessment. RESULTS: Significant
      differences between the assessment times on the physical subscale (p < 0.001),
      socio-family (p < 0.01) and emotional well-being (p < 0.001) were showed.
      Specific domain-related breast cancer and psychological distress (p < 0.05) were
      significant during the assessment period. No difference was found on the total
      quality of life score within the three points of reference for treatment. The
      regression analysis revealed that after treatment, psychological distress showed
      a higher percentage of variance of the quality of life (62.6%) compared to other
      treatment time-points. CONCLUSIONS: Significant changes to the quality of life
      and psychological distress subscales are seen during breast cancer treatment. The
      degree to which psychological distress affected quality of life varied over the
      illness continuum. Health professionals should pay attention to the variability
      of the emotional support and care needs of patients with cancer at different
      times of treatment.

PMID- 22583137
TI  - Patterns of trauma induced by motorboat and ferry propellers as illustrated by
      three known cases from Rhode Island.
AB  - Understanding patterns of trauma is important to determining cause and manner of
      death. A thorough evaluation of taphonomy, trauma, and bone fracture mechanisms
      is necessary to reconstruct the circumstances of the death. This study examines
      the skeletal trauma caused by boat propeller strikes in terms of wound
      characteristics and location based on three cases from Rhode Island. These case
      studies review the traumatic characteristics caused by propeller injuries and
      highlight the anatomic regions most likely to sustain skeletal trauma. With this
      information, investigators may be able to identify propeller trauma even in
      severely decomposed remains. The discussion of boat propeller trauma also raises
      issues regarding how forensic anthropologists and forensic pathologists classify
      trauma (specifically blunt force vs. sharp) and highlights semantic issues
      arising in trauma classification. The study also discusses why these propeller
      cases should be classified as blunt trauma rather than sharp or chop/hack trauma.
      Ultimately, the authors urge consistency and communication between pathologist
      and forensic anthropologists performing trauma analyses.

PMID- 22583138
TI  - In vitro activity on human gut bacteria of murta leaf extracts (Ugni molinae
      turcz.), a native plant from Southern Chile.
AB  - Despite the fact that murta infusions have been used to treat gut/urinary
      infections by native Chileans for centuries, the mechanisms promoting such
      effects still remain unclear. As a first attempt to unravel these mechanisms,
      human fecal samples were incubated in a medium containing water extract of murta
      leaves (ML) and the growth of different bacterial groups was evaluated. Control
      incubations were made in media containing fructooligosaccharides (FOS) and
      glucose as a carbon source. Phenolic compounds in the ML extract, likely
      promoters of bioactivity, were identified by HPLC-DAD-MS(n) . Concentrations
      (log10 CFU/mL) of bifidobacteria and lactobacilli in media containing the extract
      and FOS were 7.33 +/- 0.05/4.95 +/- 0.20 and 6.44 +/- 0.22/6.05 +/- 0.06,
      respectively. Clostridia, anaerobes and Enterobacteriaceae grew to a similar
      extent in media containing murta extract and FOS. In vitro tests (disk diffusion)
      showed that Gram-positive (Bacillus and Paenibacillaceae) and Gram-negative
      (Enterobacteriaceae) bacteria isolated from fecal samples were sensitive to both
      water and 50/50 ethanol/water extracts of ML (28.4 MUg gallic acid equivalents).
      At this concentration, the antimicrobial activity of ML extracts was
      significantly (P < 0.05) lower than that of penicillin (10 U), whereas the
      difference between activity of ML extracts and gentamicine (10 MUg) was no
      significant (P > 0.05). No evidence of dependency between the antimicrobial
      activity of ML extracts and the enzymatic capability of the sensitive strains was
      found.

PMID- 22583139
TI  - Rituximab and thalidomide combination therapy for Castleman disease.

PMID- 22583140
TI  - Primary cardiac T cell lymphoma.
AB  - We report a case of primary cardiac T-cell lymphoma. The diagnosis and management
      of this unusual primary tumor is reviewed.

PMID- 22583142
TI  - Centro-facial pigmentation in asymptomatic congenital chikungunya viral
      infection.

PMID- 22583143
TI  - Significant decrease in maternal serum concentrations of angiopoietin-1 and -2
      after delivery.
AB  - OBJECTIVE: To characterize the physiological distribution of angiopoietins (Ang)
      1 and Ang-2 and soluble endothelial cell-specific tyrosine kinase receptor-2 (Tie
      2) at term and following delivery. DESIGN: A prospective, descriptive study.
      SETTING: Helsinki University Central Hospital. POPULATION: Twenty healthy term
      pregnant women undergoing elective cesarean delivery and their newborns. METHODS:
      The concentrations were analysed by enzyme-linked immunosorbent assay in maternal
      antepartum and the first postpartum day sera, umbilical serum, amniotic fluid and
      maternal and newborn urine. MAIN OUTCOME MEASURES: Concentrations of Ang-1, Ang-1
      and Tie-2. Results. Concentrations of maternal serum Ang-1 and Ang-2 decreased
      after delivery {[median (range)]: Ang-1, from 33 (25-51) to 30 (18-49) ng/mL, p=
      0.017; and Ang-2, from 5.4 (1.8-18) to 1.4 (0.7-4.6) ng/mL, p < 0.0001}, whereas
      Tie-2 concentrations remained stable [23 (13-41) vs. 25 (14-29) ng/mL, p= 0.107].
      Compared with maternal antepartum serum, umbilical serum concentrations of Ang-1
      [46 (28-59) ng/mL, p < 0.0001] and Tie-2 [45 (21-71) ng/mL, p < 0.0001] were
      higher and those of Ang-2 similar [5.4 (1.8-18) vs. 4.2 (2.9-6.0) ng/mL; p=
      0.067]. Low concentrations of Ang-1 [1.2 (0.1-2.2) ng/mL], Ang-2 [1.1 (0.3-4.1)
      ng/mL] and Tie-2 [0.4 (0.08-0.9) ng/mL] were observed in amniotic fluid, but they
      were undetectable in newborn urine and in most of the maternal urine samples.
      CONCLUSIONS: Maternal Ang-1 and Ang-2 concentrations decreased following
      delivery. Umbilical concentrations of Ang-1 and Tie-2 were higher than the
      maternal concentrations.

PMID- 22583144
TI  - Editorial comment to clinical and imaging overview of functional adrenal
      neoplasms.

PMID- 22583145
TI  - Anti-T-cell antibodies for the treatment of acute rejection after renal
      transplantation.
AB  - INTRODUCTION: Given the central role of T cells in the alloimmune response, anti
      T-cell antibodies retain a prominent place in the treatment of renal allograft
      rejection. During the past decades, many anti-T-cell antibodies have emerged and
      subsequently left the field of solid organ transplantation, but rabbit
      antithymocyte globulin (ATG) and the humanized anti-CD52 monoclonal rat antibody
      alemtuzumab have remained. AREAS COVERED: This article reviews the literature
      about the use of ATG and alemtuzumab for the treatment of acute rejection after
      renal transplantation. Furthermore, it discusses possible side effects, including
      infusion reactions. A literature search using PubMed and Embase databases was
      undertaken using search words alemtuzumab, antithymocyte globulin, rejection,
      kidney and renal transplantation. EXPERT OPINION: Treatment of severe or steroid
      resistant renal allograft rejections with ATG is very effective, but is also
      associated with frequent infusion reactions and an increased incidence of
      infections and posttransplant lymphoproliferative disease. Alemtuzumab may prove
      to be an attractive alternative. It can be administered easily, is relatively
      cheap and nearly devoid of acute side effects, but the long-term efficacy and
      safety as anti-rejection treatment are currently difficult to judge. The
      increasing knowledge about lymphocyte subsets and their plasticity will drive the
      development of new, specific immunosuppression that lacks side effects of ATG and
      alemtuzumab. TOL101, a monoclonal antibody specifically directed against the
      human alphabeta T cell receptor, might be of potential value.

PMID- 22583146
TI  - Therapeutic potential of Terminalia arjuna in cardiovascular disorders.
AB  - The bark of the tree Terminalia arjuna (Roxb.) is widely used in Indian medicine
      (Ayurveda) for various cardiovascular ailments. The bark has been reported to
      contain several bioactive compounds. Many experimental studies have reported its
      antioxidant, anti-ischemic, antihypertensive, and antihypertrophic effects, which
      have relevance to its therapeutic potential in cardiovascular diseases in humans.
      Several clinical studies have reported its efficacy mostly in patients with
      ischemic heart disease, hypertension, and heart failure. However, a major
      shortcoming in all these experimental and clinical studies is the absence of
      phytochemical standardization of the extracts. In addition, many clinical studies
      are poor in terms of design and methods used for generating safety data. This
      review discusses how to address all these issues for a scientific validation of
      this medicinal plant.

PMID- 22583147
TI  - Epidemiology and management of hypertension in the Hispanic population: a review
      of the available literature.
AB  - Hispanics are the fastest growing ethnic minority in the USA. Among Hispanics,
      lack of hypertension awareness and lack of effective blood pressure (BP) control
      are problematic, as are higher incidence rates of hypertension-related co
      morbidities compared with non-Hispanic populations. Moreover, there are currently
      no hypertension treatment guidelines that address the unique characteristics of
      this ethnic group. This article discusses ethnic differences in hypertension and
      cardiovascular risk factors and reviews the literature on the efficacy of
      antihypertensive agents in Hispanic patients, with a focus on the role of renin
      angiotensin-aldosterone system (RAAS) inhibition in the management of
      hypertension in these patients. Hypertension in Hispanic patients can be
      challenging to manage, in part because this population has a higher prevalence of
      obesity, diabetes, and metabolic syndrome compared with non-Hispanic whites. The
      presence of these co-morbidities suggests that RAAS-inhibitor-based therapies may
      be particularly beneficial in this population. However, few studies have
      evaluated the efficacy of antihypertensive treatments in Hispanic patients. Two
      outcomes studies in hypertensive patients have shown the benefits of treating
      Hispanic patients with antihypertensive therapy and included RAAS inhibitors as
      part of the treatment regimen. In addition, BP-lowering trials have shown the
      antihypertensive efficacy of angiotensin-converting enzyme inhibitors,
      angiotensin II receptor blockers, and direct renin inhibitors, although data on
      the latter are more limited. Additional studies are needed to more thoroughly
      evaluate the effects of RAAS inhibitors (and other drug classes) on outcomes and
      BP lowering in the Hispanic hypertensive population.

PMID- 22583149
TI  - Oxidation state of uranium in A6Cu12U2S15 (A = K, Rb, Cs) compounds.
AB  - Black single crystals of A(6)Cu(12)U(2)S(15) (A = K, Rb, Cs) have been
      synthesized by the reactive flux method. These isostructural compounds
      crystallize in the cubic space group Ia 3d at room temperature. The structure
      comprises a three-dimensional framework built from US(6) octahedra and CuS(3)
      trigonal planar units with A cations residing in the cavities. There are no S-S
      bonds in the structure. To elucidate the oxidation state of U in these compounds,
      various physical property measurements and characterization methods were carried
      out. Temperature-dependent electrical resistivity measurement on a single crystal
      of K(6)Cu(12)U(2)S(15) showed it to be a semiconductor. These three
      A(6)Cu(12)U(2)S(15) (A = K, Rb, Cs) compounds all exhibit small effective
      magnetic moments, < 0.58 MU(B)/U and band gaps of about 0.55(2) eV in their
      optical absorption spectra. From X-ray absorption near edge spectroscopy (XANES),
      the absorption edge of A(6)Cu(12)U(2)S(15) is very close to that of UO(3).
      Electronic band structure calculations at the density functional theory (DFT)
      level indicate a strong degree of covalency between U and S atoms, but theory was
      not conclusive about the formal oxidation state of U. All experimental data
      suggest that the A(6)Cu(12)U(2)S(15) family is best described as an intermediate
      U(5+)/U(6+) sulfide system of (A(+))(6)(Cu(+))(12)(U(5+))(2)(S(2-))(13)(S(-))(2)
      and (A(+))(6)(Cu(+))(12)(U(6+))(2)(S(2-))(15).

PMID- 22583148
TI  - Prasugrel: a guide to its use in patients with acute coronary syndromes
      undergoing percutaneous coronary intervention in the US.
AB  - Oral prasugrel (Effient((r)); Efient((r))) provides rapid, potent inhibition of
      platelet aggregation. It is indicated (in combination with aspirin) for the
      prevention of atherothrombotic events in patients with acute coronary syndromes
      (ACS) undergoing percutaneous coronary intervention (PCI). In the pivotal
      clinical trial in this patient population, prasugrel-based therapy was associated
      with a significantly lower incidence of ischemic events than clopidogrel-based
      therapy. However, the efficacy of prasugrel was offset by a higher risk of
      bleeding than clopidogrel, with patients aged >=75 years, those weighing <60 kg
      and those with a history of stroke or transient ischemic attack at the greatest
      risk. Prasugrel appears to have an overall favorable risk : benefit ratio in ACS
      patients undergoing PCI who do not have these three easily identifiable clinical
      characteristics. Limited pharmacoeconomic analyses suggest that prasugrel-based
      therapy is an economically attractive treatment strategy relative to clopidogrel
      based therapy from a US healthcare payer perspective.

PMID- 22583150
TI  - The early years of Drosophila chemosensory genetics in Mumbai's Tata Institute of
      Fundamental Research.
AB  - Some of the very first chemosensory mutants in Drosophila were generated in
      screens done in the 1970s at Obaid Siddiqi's lab in Tata Institute of Fundamental
      Research (TIFR), Mumbai. This is a personal account of some of the early work
      with these mutants, which led to their physiological and molecular
      characterization. The author also touches upon the significance of these mutants
      for understanding subsequent work in Drosophila chemosensory biology.

PMID- 22583151
TI  - Superoxide dismutase 3 controls adaptive immune responses and contributes to the
      inhibition of ovalbumin-induced allergic airway inflammation in mice.
AB  - AIMS: The extracellular superoxide dismutase 3 (SOD3) is an isoform of SOD.
      Extensive studies have been focused on role of SOD3 as an antioxidant. However,
      the role of SOD3 in the immune responses that contribute to the inhibition of
      allergic lung inflammation has not been investigated. RESULTS: Here, we report
      for the first time that SOD3 specifically inhibits dendritic cell maturation.
      Subsequently, SOD3 controls T cell activation and proliferation, and T helper 2
      (Th2) and Th17 cell differentiation. As a consequence, the administration of SOD3
      into mice alleviated Th2-cell-mediated ovalbumin (OVA)-induced allergic asthma.
      In addition, we demonstrated that SOD3 inhibits OVA-induced airway extracellular
      remodeling and Th2 cell trafficking. Through mass spectrometry analysis, the
      proteins interacting with SOD3 in the lung of asthma were identified. And it was
      revealed that signaling molecules, such as transforming growth factor (TGF) and
      epidermal growth factor (EGF) receptor, adhesion and adaptor molecules, kinases,
      phosphatases, NADPH oxidase, and apoptosis-related factor, were involved, which
      were altered by administration of SOD3. Relatively severe asthma was observed in
      SOD3 KO mice and was ameliorated by both the administration of SOD3 and adoptive
      transfer of SOD3-sufficient CD4 T cells. Moreover, the expression of endogenous
      SOD3 in the lung peaked early in OVA challenge and gradually decreased upon
      disease progression, while both SOD1 and SOD2 expression changed relatively
      little. INNOVATION AND CONCLUSION: Thus, our data suggest that SOD3 is required
      to maintain lung homeostasis and acts, at least in part, as a controller of
      signaling and a decision maker to determine the progression of allergic lung
      disease.

PMID- 22583152
TI  - A clinical tool to measure the components of health-care transition from
      pediatric care to adult care: the UNC TR(x)ANSITION scale.
AB  - OBJECTIVE: To describe the development of the University of North Carolina (UNC)
      TR(x)ANSITION Scale that measures the health-care transition and self-management
      skills by youth with chronic health conditions. METHODS: Item and scale
      development of the UNC TR(x)ANSITION Scale was informed by two theoretical
      models, available literature, and expert opinion interviews and feedback from
      youth with chronic conditions, their parents, and interdisciplinary
      collaboration. Through an iterative process, three versions of the scale were
      piloted on a total of 185 adolescents and emerging adults with different chronic
      illnesses. This clinically administered scale relies on a semi-structured
      interview format of the patient and does not rely solely on patient report, but
      is verified with information from the medical record to validate responses.
      RESULTS: Following the item development and the three iterations of the scale,
      version 3 was examined in a more intensive fashion. The current version of the
      UNC TR(x)ANSITION Scale comprises 33 items scattered across the following 10
      domains: Type of illness, Rx=medications, Adherence, Nutrition, Self-management,
      Informed-reproduction, Trade/school, Insurance, Ongoing support, and New health
      providers. It requires approximately 7-8 min to administer. With a sample of 128
      adolescents and young adults, ranging in age from 12 to 20, inter-rater
      reliability was strong (r = 0.71) and item-total correlation scores were moderate
      to high. Content and construct validity were satisfactory, and the overall score
      was sensitive to advancing age. The univariate linear regression yielded a beta
      coefficient of 1.08 (p < 0.0001), indicating that the total score increased with
      advancing age. Specifically, there was about a one point increase in the total
      score for each year of age. CONCLUSION: The UNC TR(x)ANSITION Scale is a disease
      neutral tool that can be used in the clinical setting. Initial findings suggest
      that it is a reliable and valid tool that has the potential to measure health
      care transition skill mastery and knowledge in a multidimensional fashion.

PMID- 22583154
TI  - Life-sharing experiences of relatives of persons with severe mental illness - a
      phenomenographic study.
AB  - Relatives of those suffering from severe mental illness experience multiple
      challenges and a complex life situation. The aim of this study was to describe
      life-sharing experiences from the perspective of relatives of someone with severe
      mental illness. A qualitative, descriptive study was performed, and interviews
      were carried out with eighteen relatives of persons with severe mental illness. A
      phenomenographic analysis, according to the steps described by Dahlgren and
      Fallsberg, was used to describe the relatives' conceptions of their situation.
      The findings show that the experiences of these relatives can be summarized in
      one main category: 'The art of balancing between multiple concerns'. Two
      descriptive categories emerged: 'Making choices on behalf of others and oneself'
      and 'Constantly struggling between opposing feelings and between reflections'.
      Relatives report that they have to manoeuvre between different ways to act and to
      prioritize between different wishes and needs. In addition, they face a wide
      range of strong feelings and they search for hope and meaning. Relatives of
      someone with severe mental illness have to balance multiple concerns, which
      induce ethical dilemmas. They felt love, compassion or sense of duty towards the
      mentally ill person. The changeable situation made it difficult for the relatives
      to establish a balance in their lives. To be able to prioritize some private time
      was important. Relatives need own support and sufficient follow-up of the
      mentally ill next of kin from the mental health services.

PMID- 22583153
TI  - Prenatal exposure to allergen, DNA methylation, and allergy in grandoffspring
      mice.
AB  - BACKGROUND: Prenatal allergen exposure has been linked to both induction and
      protection of allergic sensitization in offspring. We hypothesized that prenatal
      exposure of mice (F0) to Aspergillus fumigatus (A. fumigatus) would be associated
      with decreased immunoglobulin (Ig) E and airway eosinophilia and alterations in
      CpG methylation of T-helper genes in third-generation mice (F2). METHODS: Female
      BALB/c mice were sensitized to A. fumigatus (62.5, 125, 1250 MUg, or saline) and
      re-exposed to the same dose on days 7 and 14 (early) or days 12 and 17 (late)
      gestation. Grandoffspring were treated with A. fumigatus (62.5 MUg) at 9 weeks.
      IgE, IgG(1) , and IgG(2a) levels and cell counts from bronchoalveolar lavage
      fluid were determined. Lung DNA was pyrosequenced at multiple sites in the
      interferon (IFN)-gamma and interleukin (IL)-4 promoters. RESULTS: Grandoffspring
      of mothers dosed with 1250 MUg early during pregnancy developed increased airway
      eosinophilia (P < 0.05). Grandoffspring of mothers dosed late in pregnancy
      developed lower IgE (P < 0.05) and airway eosinophilia (P < 0.05). Grandoffspring
      of mothers dosed early had lower methylation at IL-4 CpG(-408) and CpG(-393)
      compared to late dosed mice (P < 0.005 across all doses). Few correlations were
      found between methylation levels and airway eosinophilia and IgE. CONCLUSION:
      Prenatal exposure to A. fumigatus late during pregnancy, but not early, was
      associated with lower IgE and airway eosinophilia in grandoffspring. Prenatal
      exposure to A. fumigatus was associated with changes in CpG methylation in the
      IFN-gamma and IL-4 promoters that did not correlate consistently with indicators
      of allergic sensitization.

PMID- 22583155
TI  - Gantenerumab  for the treatment of Alzheimer's disease.
AB  - IMPORTANCE OF THE FIELD: Alzheimer's disease is the leading cause of dementia in
      the elderly, and there is no disease-modifying therapy yet available.
      Immunotherapy directed against the beta-amyloid peptide may be capable of slowing
      the rate of disease progression. Gantenerumab is the first fully human anti-beta
      amyloid monoclonal antibody. AREAS COVERED: To review the efficacy and safety of
      immunotherapy drugs and in particular gantenerumab, we used the database MEDLINE.
      The primary literature on gantenerumab is reviewed in its entirety. We also
      reviewed the English-language, pre-clinical and clinical trials designed to
      evaluate the efficacy or/and safety of immunotherapy drugs, from 1999 through
      2011. Other Alzheimer's disease-passive immunotherapeutics currently in
      development, according to www.clinicaltrials.gov, are also discussed. EXPERT
      OPINION: Gantenerumab appears capable of reducing the cerebral beta-amyloid
      peptide burden in patients with Alzheimer's disease. Its ability to slow disease
      progression remains uncertain because no clinical data are available at present.
      The next step will be to investigate whether removal of brain amyloid translates
      into clinical benefit for patients at doses of gantenerumab that reduce brain
      amyloid and are well tolerated.

PMID- 22583156
TI  - Impact of the emergence of non-vaccine pneumococcal serotypes on the clinical
      presentation and outcome of adults with invasive pneumococcal pneumonia.
AB  - The introduction of the 7-valent pneumococcal conjugate vaccine in children has
      led to a change in the pattern of pneumococcal serotypes causing pneumococcal
      disease. The aim of this study was to compare the clinical presentation and
      outcome of invasive pneumococcal pneumonia (IPP) in adults between the pre and
      post-vaccine era. We have conducted an observational study of all adults
      hospitalized with IPP, from 1996 to 2001 (pre-vaccine period), and from 2005 to
      2009 (post-vaccine period). Incidence, serotype distribution and clinical data
      were compared between both periods. A total of 653 episodes of IPP were
      diagnosed. The overall incidence of IPP increased from 14.2 to 17.9 cases per 100
      000 population-year (p 0.003). In the post-vaccine period IPP caused by vaccine
      serotypes decreased (-36%; 95% CI, -52 to -15) while IPP caused by non-vaccine
      serotypes increased (71%; 95% CI, 41-106). IPP in the post-vaccine period was
      associated with higher rates of septic shock (19.1% vs. 31.1%, p <0.001). Among
      patients aged 50-65 years there was a trend towards a greater proportion of case
      fatalities (11.6-23.5%, p 0.087). Independent risk factors for septic shock were
      IPP caused by serotype 3 (OR 2.38; 95% CI, 1.16-4.87) and serotype 19A (OR 6.47,
      95% CI, 1.55-27). Serotype 1 was associated with a lower risk of death (OR 0.1;
      95% CI, 0.01-0.78). In conclusion, the incidence of IPP in the post-vaccine
      period has increased in our setting, it is caused mainly by non-vaccine serotypes
      and it is associated with higher rates of septic shock.

PMID- 22583157
TI  - Ultrasonographic identification of vascular invasion by adrenal tumors in dogs.
AB  - Adrenalectomy is the treatment of choice for adrenal tumors that are producing
      adverse clinical signs. Surgical planning prior to adrenalectomy is aided by
      identifying tumors with invasion into adjacent vessels or the presence of a tumor
      thrombus extending into the caudal vena cava. In this paper, we evaluated the
      sensitivity and specificity of ultrasound in determining if vascular invasion or
      tumor thrombus is present. Thirty-four dogs with 36 adrenal tumors were reviewed
      retrospectively. Overall, 36% of tumors had vascular invasion. Abdominal
      ultrasound was 100% sensitive and 96% specific in identifying the presence of a
      tumor thrombus in the caudal vena cava. The sensitivity and specificity was 76%
      and 96%, respectively, when all forms of vascular invasion were evaluated and
      included patients with vascular wall invasion without concurrent thrombus.
      Abdominal ultrasound is a good screening tool for identifying vascular invasion
      or tumor thrombus associated with adrenal tumors in dogs.

PMID- 22583159
TI  - Intrathecal shRNA-AAV9 inhibits target protein expression in the spinal cord and
      dorsal root ganglia of adult mice.
AB  - Gene therapy for neurological diseases requires efficient gene delivery to target
      tissues in the central and peripheral nervous systems. Although adeno-associated
      virus is one of the most promising vectors for clinical use against neurological
      diseases, it is difficult to get it across the blood-brain barrier. A clinically
      practical approach to using a vector based on adeno-associated virus to decrease
      the expression of a specific gene in both the central and the peripheral nervous
      system has yet to be established. Here, we analyzed whether upper lumbar
      intrathecal administration of a therapeutic vector incorporating adeno-associated
      virus and short-hairpin RNA against superoxide dismutase-1 bypassed the blood
      brain barrier to target the spinal cord and dorsal root ganglia. The therapeutic
      vector effectively suppressed mRNA and protein expression of endogenous
      superoxide dismutase-1 in the lumbar spinal cord and dorsal root ganglia.
      Moreover, neither neurological side effects nor toxicity due to the incorporated
      short-hairpin RNA occurred after the injection. We propose that this approach
      could be developed into novel therapies for motor neuron diseases and chronic
      pain conditions, such as complex regional pain syndrome, through silencing of the
      genes responsible for pathologies in the spinal cord and dorsal root ganglia.

PMID- 22583160
TI  - Translocation and cross-contamination of E. coli O157 in beef eye-of-round
      subprimal cuts processed with high-pressure needleless injection.
AB  - High-pressure needleless injection (HPNI) is an emerging enhancing process where
      small-diameter, high-velocity bursts of liquid penetrate soft foods at pressures
      up to 69 MPa. The incidence and depth of translocated surface-inoculated E. coli
      O157 in HPNI-processed beef eye-of-round subprimal cuts was determined. HPNI
      translocated E. coli O157 from the surface to the interior of the eye-of-round
      subprimal cuts with incidence of 40% (+/- 7%), 25% (+/- 8%), and 25% (+/- 8)% for
      subprimals that had been surface-inoculated with a 4-strain cocktail at 0.5, 1,
      and 2 log10 CFU/cm2 , respectively. The run-off water was collected and found to
      contain 2, 2, and 3 log10 CFU/mL E. coli O157. The runoff was reused for HPNI of
      additional subprimals, and this resulted in a cross-contamination incidence of
      83% (+/- 4%), 60% (+/- 15%), and 37% (+/- 6)%. Incidence of translocation and
      cross-contamination was similar at 0 to 1, 1 to 2, 2 to 3, 3 to 4, 4 to 6, and 6
      to 8 cm below the inoculated surface. Results indicate that surface microbiota on
      beef will be carried to the interior of HPNI-processed beef by initial
      translocation from the surface with the injected fluid and by cross-contamination
      with recycled fluid. PRACTICAL APPLICATION: This research has practical relevance
      for the beef enhancement process called high-pressure needleless injection. The
      process's effect on surface bacteria on beef was studied.

PMID- 22583161
TI  - Obaid Siddiqi and the justification for giving neuroscience courses in countries
      with little money for research.
AB  - This article deals with the aims and achievements of intensive lecture and
      laboratory courses given in countries with very little money available for
      research in neurobiology.

PMID- 22583164
TI  - Willingness to pay and quality of life in patients with rosacea.
AB  - BACKGROUND: Rosacea is a chronic inflammatory dermatosis affecting >2% of the
      population. Willingness to pay (WTP) is a well established method which reflects
      the individual burden of disease. OBJECTIVES: Evaluation of WTP and quality of
      life (QoL) in patients with rosacea. METHODS: Nationwide postal survey on adult
      patients with rosacea affiliated with the German rosacea patient advocacy group.
      WTP was evaluated by three standardized items and compared to historical data on
      vitiligo (n = 1023). QoL was assessed using the Dermatology Life Quality Index
      (DLQI). RESULTS: Data from n = 475 rosacea patients (79.9% women, mean age 56.3,
      range 26-90) were analysed. On average, patients were willing to pay ? 2880
      (median ? 500) for complete healing compared with ? 7360 (median ? 3000) in
      vitiligo. Relative WTP was higher in women; the highest sums were registered for
      the age group 21-30 years. The extent of facial involvement predicted a higher
      relative WTP, whereas WTP decreased with the duration of symptoms and age. Mean
      DLQI total score was 4.3 compared to 7.0 in vitiligo. In rosacea, the highest
      values were observed in patients <30 years. Severe QoL reductions (DLQI>10) were
      less frequent (11%) than in vitiligo (24.6%). The correlation between WTP and
      DLQI was significant (e.g. r = 0.249, P = 0.000 for relative WTP). CONCLUSION:
      Rosacea patients show a moderate WTP and average QoL reduction is mild. WTP
      proved to be a valid tool to assess patients' burden of disease. Patient
      education and the development of effective treatment options might still improve
      patients' satisfaction.

PMID- 22583165
TI  - Australian emergency doctors' and nurses' acceptance and knowledge regarding
      brain death: a national survey.
AB  - Healthcare staff's acceptance of brain death (BD) being a valid determination of
      death is essential for optimized organ and tissue donation (OTD) rates. Recently,
      resources to increase Australian OTD rates have been aimed at emergency
      departments (ED) as a significant missed donor potential was discovered. A cross
      sectional survey was conducted to assess Australian ED clinicians' acceptance and
      knowledge regarding BD. Most (86%) of the 599 medical and 212 nursing staff
      accepted BD, but only 60% passed a 5-item-validated BD knowledge tool. BD
      knowledge was related to the acceptance of BD. Accepting BD influenced attitudes
      toward OTD, including willingness to donate. BD acceptance and knowledge were
      related to education/training regarding OTD, years of experience in EDs,
      experience with OTD-related tasks, and increased perceived competence and comfort
      with OTD-related tasks. Of concern, more than half of respondents who did not
      pass the BD test reported feeling competent and comfortable explaining BD to next
      of kin; of respondents who had recent experience with this, more than a third
      failed the BD test. Despite being generally positive toward OTD, Australian ED
      clinicians do not have a sound knowledge of BD. This may be hampering efforts to
      increase donation rates from the ED.

PMID- 22583166
TI  - Remodeling of nucleosome-dimer particles with yIsw2 promotes their association
      with ALL-1 SET domain in vitro.
AB  - Functioning of histone lysine methyltransferases (HKMTs) involves interactions of
      their catalytic domain "SET" with the N-termini of histone H3. However, these
      interactions are restricted in canonical nucleosomes due to the limited
      accessibility of H3 termini. Here we investigated whether nucleosome remodeling
      with the yeast Isw2 affects nucleosome affinity to the SET domain of ALL-1 HKMT.
      Reconstitution of mononucleosomes by salt dilutions also produces some nucleosome
      dimer particles (self-associated mononucleosomes, described by: Tatchell and van
      Holde (1977) Biochemistry, 16, 5295-5303). The GST-tagged SET-domain polypeptide
      of ALL-1 was assayed for binding to assembled mononucleosomes and nucleosome
      dimer particles, either intact or remodeled with purified yeast Isw2. Remodeling
      of mononucleosomes does not noticeably affect their affinity to SET domain;
      however, yIsw2 remodeling of nucleosome-dimer particles facilitated their
      association with GST-SET polypeptide. Therefore, it is conceivable that
      nucleosome interactions in trans could be implicated in the maintenance of
      chromatin methylation patterns in vivo.

PMID- 22583167
TI  - Metallopolymeric films based on a biscyclometalated ruthenium complex bridged by
      1,3,6,8-tetra(2-pyridyl)pyrene: applications in near-infrared electrochromic
      windows.
AB  - A biscyclometalated ruthenium complex bridged by the 2,7-deprotonated form of
      1,3,6,8-tetra(2-pyridyl)pyrene was deposited onto indium-tin oxide glass
      electrodes by reductive electropolymerization. The resulting metallopolymeric
      films exhibited tricolor electrochromic behavior in the near-infrared region upon
      switching of the two well-separated Ru(II/III) processes at low potentials. A
      good contrast ratio (35%) at 2050 nm and a long memory time up to 100 min were
      recorded for this electrochromic behavior. The response time is typically of a
      few seconds.

PMID- 22583168
TI  - Influenza A/H1N1 (2009) infection as a cause of unexpected out-of-hospital death
      in the young.
AB  - In March 2009, a new strain of influenza A/H1N1 virus was identified in Mexico,
      responsible for a pandemic. Worldwide, more than 13,500 patients died, most often
      from acute respiratory distress syndrome. Because sudden death cases were rare,
      involving mostly young apparently healthy persons, influenza A/H1N1 (2009)
      related deaths may be misdiagnosed, which can raise medico-legal issues. CASE
      HISTORY: we report on an unexpected out-of-hospital death involving a young male
      with no past medical history and no vaccination. Fever was his only symptom.
      Laboratory tests: histology showed patchy necrotic foci with mononuclear
      inflammation in the lungs. The heart was histologically normal, but virological
      analyses using molecular biology on frozen myocardial samples showed high virus
      load. In conclusion, this case report shows that influenza A/H1N1 (2009) virus
      can be a cause of sudden cardiac death in the young and demonstrates the
      importance of quantitative virological analyses for the diagnosis of myocarditis.

PMID- 22583169
TI  - Renalase, stroke, and hypertension in hemodialyzed patients.
AB  - INTRODUCTION: Hypertension and kidney disease have been associated with increased
      incidence of stroke. Renalase, a newly discovered hormone, is secreted by the
      kidney and circulates in blood. The aim of this study was to assess possible
      correlations between renalase, blood pressure, stroke, and cardiovascular status
      in prevalent hemodialyzed patients. METHODS: Renalase was assessed using
      commercially available assay. Echocardiography was performed in each patient.
      RESULTS: Serum renalase was significantly lower in patients with a history of
      stroke (21%) than in patients without it. Similarly, renalase was significantly
      lower in hypertensive patients (82%) when compared with normotensives. Serum
      renalase correlated with creatinine, residual renal function, and transferrin
      saturation. The only predictor of renalase in multiple regression analysis was
      the presence of hypertension explaining 90% of the renalase variations.
      CONCLUSIONS: Our preliminary results suggest that renalase, probably due to the
      sympathetic nervous system hyperactivity, could be associated with hypertension
      and cardiovascular complications, including stroke in hemodialyzed patients.
      However, further studies are needed to establish the possible role of renalase in
      these complications. Renalase is "a new postulated therapeutic target."

PMID- 22583170
TI  - Traumatic brain injury in Spanish-speaking individuals: research findings and
      clinical implications.

PMID- 22583171
TI  - Preliminary investigation of longitudinal sociodemographic, injury and
      psychosocial characteristics in a group of non-English speaking Latinos with
      brain injury.
AB  - PRIMARY OBJECTIVE: To describe the sociodemographic and injury characteristics
      and psychosocial outcomes at 1 and 10 years post-injury in a group of Spanish
      speaking individuals with traumatic brain injury. RESEARCH DESIGN: Descriptive
      cross-sectional and longitudinal analyses of prospectively collected data.
      METHODS AND PROCEDURES: Assessments were completed on 57 non-English speaking
      Latinos with TBI, injured between March 1991 and January 2008, who were treated
      at a Traumatic Brain Injury Model System of Care acute rehabilitation facility.
      Follow-up data was collected cross-sectionally at 1 year (n = 41) and 10 years (n
      = 23) post-injury. Longitudinal data (both Y1 and Y10) were available for 17 of
      those individuals. MAIN OUTCOMES: Post injury employment and residence,
      Disability Rating Scale, Functional Independence Measure. RESULTS: At 1 year, the
      majority of participants were unemployed (63.4%) and did not require assistance
      of another individual (58.5%) as measured by the DRS Level of Functioning. FIM
      scores showed that the greatest difficulty was in the area of problem-solving and
      memory with over half the sample needing assistance in these areas. At 10 years
      post-injury, 47.8% were unemployed and remained independent of assistance from a
      caretaker (56.5%) as measured by the DRS. FIM results revealed that slightly less
      than half continued to need assistance in areas of problem-solving and memory.
      Longitudinal changes were seen in that, over time, individuals reported more
      difficulties in areas of bathing and dressing, but fewer difficulties in areas
      including social interaction, comprehension and memory. CONCLUSIONS: Non-English
      speaking Latinos with brain injury are at a double disadvantage with regard to
      obtaining much-needed ongoing services, ultimately impacting long-term outcomes
      post-injury. If such issues are not adequately addressed, as the Latino
      population continues to grow, disparities in service delivery and unsuccessful
      outcomes will continue to grow.

PMID- 22583172
TI  - Neurobehavioural symptoms 1 year after traumatic brain injury: a preliminary
      study of the relationship between race/ethnicity and symptoms.
AB  - OBJECTIVE: To investigate whether White, African American and Hispanic
      individuals with a traumatic brain injury (TBI) express differences in
      neurobehavioural symptoms at 1 year post-injury after adjusting for demographic
      and injury characteristics. DESIGN: Retrospective study. PARTICIPANTS: One
      thousand, three hundred and thirty-nine individuals from the TBI Model Systems
      National Database with primarily moderate-to-severe TBI (978 White, 288 African
      American and 73 Hispanic) hospitalized between 1996 and 2001. MAIN OUTCOME
      MEASURES: Neurobehavioural Functioning Inventory (NFI) at 1 year post-injury.
      RESULTS: There were significant differences in NFI scores among the
      races/ethnicities for the depression, somatic, memory/attention, communication
      and motor subscales, after adjusting for demographic and injury characteristics;
      there were not significant differences in the aggression sub-scale. Hispanics had
      higher levels of symptom reporting than African Americans and Whites, while
      differences between African Americans and Whites were not significant.
      CONCLUSIONS: Hispanics scored significantly higher than Whites and African
      Americans on the sub-scales of the NFI, indicating more problems in these areas.
      Future research should focus on identifying factors that may contribute to the
      difference between the groups and treatment interventions should be implemented
      accordingly.

PMID- 22583173
TI  - Health-related quality of life of individuals with traumatic brain injury in
      Barranquilla, Colombia.
AB  - OBJECTIVE: To assess health-related quality of life (HRQoL) of individuals with
      traumatic brain injury (TBI) in Barranquilla, Colombia. PARTICIPANTS/METHODS:
      Thirty-one individuals with TBI and 61 healthy controls completed the SF-36, a
      self-report HRQoL measure composed of eight component areas: physical health
      problems, pain, role limitations due to physical problems or due to emotional
      problems, emotional well-being, social functioning, energy/fatigue and general
      health perceptions. RESULTS: The samples were statistically similar with respect
      to age, gender and education and statistically different with respect to
      depression, SES, social support and cognition. Compared to healthy controls,
      individuals with TBI had significantly lower means on all SF-36 sub-scales.
      However, after adjusting for depression, SES, social support and cognitive
      performance, significant differences remained on three of the SF-36 sub-scales.
      Specifically, individuals with TBI had lower adjusted means on Role-Physical (p
      value < 0.005), Role-Emotional (p-value < 0.005) and Bodily Pain (p-value <
      0.05). CONCLUSION: Even after controlling for depression, SES, social support and
      cognitive performance, individuals with TBI living in Barranquilla Colombia
      report having poorer quality of life across various domains, including Role
      Physical, Role-Emotional and Bodily Pain. These findings suggest the need for
      rehabilitation health professionals to develop and implement culturally
      appropriate interventions to improve quality of life in Colombian individuals
      with TBI.

PMID- 22583174
TI  - Depression and grief in Spanish family caregivers of people with traumatic brain
      injury: the roles of social support and coping.
AB  - PURPOSE: To examine the associations between social support, coping responses and
      depressive and grief symptoms in caregivers of people with traumatic brain injury
      (TBI). METHODS AND PROCEDURES: A cross-sectional study of Spanish primary
      caregivers of individuals with TBI. The study included 223 caregivers (72.2%
      female and 26.9% male). MAIN OUTCOMES: Measures administered included the Family
      Needs Questionnaire, the Texas Revised Inventory of Grief, the Centre for
      Epidemiological Studies Depression Scale and the Responses to Stress
      Questionnaire. RESULTS: A structural equation model indicated that secondary
      control coping (e.g. acceptance and positive thinking) was associated with less
      grief and depressive symptoms, whereas primary control coping (e.g. problem
      solving and emotional expression) and disengagement were associated with more
      symptoms. Emotional and instrumental supports were directly associated with less
      depressive symptoms. In addition, emotional and professional supports were
      associated with symptoms through the use of primary control and disengagement
      coping. CONCLUSIONS: These results indicate that future interventions with
      families should improve social networks of emotional, instrumental and
      professional support, as well as help caregivers to develop adaptive coping
      strategies, such as acceptance and positive thinking.

PMID- 22583175
TI  - Preliminary validation of the Spanish version of the Frontal Systems Behavior
      Scale (FrSBe) using Rasch analysis.
AB  - PRIMARY OBJECTIVE: To explore the construct validity of the Spanish version of
      the Frontal Systems Behavioral Scale (FrSBe) using Rasch modelling. METHODS: Item
      responses of 245 Spanish subjects were analysed using Rasch analysis: self-rating
      of 65 participants with TBI or stroke (sample A), family-rating of the same 65
      participants (sample B) and self-rating of 115 healthy individuals (sample C).
      RESULTS: After removing or grouping several problematic items, the Apathy and the
      Executive Dysfunction sub-scales were found to be valid measures for samples A
      and B and the Disinhibition sub-scale was valid for samples B and C. Person
      Separation Index of reliability of sub-scales was greater than 0.83 for sample B
      and ~0.72 for A and C. All items showed disordered threshold categories in
      samples A and B and five items were ordered in sample C. CONCLUSIONS: With a few
      modifications, the sub-scales of the FrSBe-Spanish version are adequate measures
      for the assessment of the behavioural syndromes derived from frontal systems
      dysfunction in persons with brain injury. The family-rating form is preferable to
      the self-rating form. Only the Disinhibition scale is a valid measure for the
      behavioural assessment of the normal population. A reduction of response
      categories is suggested.

PMID- 22583176
TI  - Assessing sub-optimal performance with the Test of Memory Malingering in Spanish
      speaking patients with TBI.
AB  - PRIMARY OBJECTIVES: To examine the clinical utility of the Test of Memory
      Malingering (TOMM) with US Spanish speaking patients diagnosed with traumatic
      brain injury (TBI). RESEARCH DESIGN: The demographic characteristics and
      neuropsychological functioning of Spanish speaking patients with TBI with valid
      vs suboptimal performance were compared. METHODS AND PROCEDURES: Demographic and
      neuropsychological data were retrospectively collected from charts of patients
      who underwent neurocognitive evaluations for clinical, med-legal and workmen's
      compensation purposes. Slick et al. criteria for malingered neurocognitive
      dysfunction were employed for clinical determination of the validity of
      participants' neuropsychological profiles, resulting in 16 valid and four
      suboptimal performers. MAIN OUTCOMES AND RESULTS: Valid performers obtained
      significantly greater scores than suboptimal performers on all trials of the TOMM
      and generally demonstrated less impairment across neuropsychological domains. The
      traditional cut-off score for the TOMM misclassified 18.8% of participants not
      suspected of malingering and lower levels of education appeared to reduce
      performance on this measure within the valid group. CONCLUSIONS: The current
      findings generally support the use of the TOMM with US primarily Spanish speaking
      patients diagnosed with TBI. However, caution is recommended when utilizing this
      measure with individuals having minimal levels of education. Future research with
      a larger sample and a non-neurological age- and education-matched sample should
      investigate lower cut-off scores for use with such patients.

PMID- 22583177
TI  - Do traditional executive measures tell us anything about daily-life functioning
      after traumatic brain injury in Spanish-speaking individuals?
AB  - PRIMARY OBJECTIVE: To examine the relationship between traditional executive
      function measures and everyday competence in Spanish-speaking individuals with
      moderate-to-severe traumatic brain injury (TBI). METHODS AND PROCEDURES: Thirty
      two TBI patients (24 men, eight women) with an age range of 17-59 years (mean age
      = 30.73 years; SD = 13.34) were administered a battery of performance-based
      executive function measures. Such measures included the Trail Making Test part B,
      Wisconsin Card Sorting Test, Stroop Colour Word Interference Test, Controlled
      Oral Word Association Test and Letter-Number Sequencing. Behavioural
      manifestations of executive deficits were assessed by the Behaviour Rating
      Inventory of Executive Function-Adult version (BRIEF-A). Patient's everyday
      functioning was examined with the Patient Competency Rating Scale (PCRS). MAIN
      OUTCOMES AND RESULTS: Traditional performance-based executive measures correlated
      significantly, although moderately, with the PCRS; this relationship was more
      significant in the Controlled Oral Word Association Test and Trail Making Test
      part B. A significant correlation was obtained between the BRIEF-A clinical
      scales and patient's everyday competence as measured by the PCRS. CONCLUSIONS:
      The current findings suggest that traditional performance-based executive
      measures reveal some degree of ecological validity or real-world relevance,
      providing relevant information for predicting everyday competence after moderate
      to-severe TBI.

PMID- 22583178
TI  - The usefulness of self-generation to improve learning and memory in Spanish
      speaking individuals with traumatic brain injury from Colombia.
AB  - OBJECTIVE: To examine the effect of self-generation on learning and memory in
      Spanish-speaking individuals with traumatic brain injury (TBI). METHOD: Thirty
      Spanish-speaking individuals with moderate-to-severe TBI and 31 healthy controls
      were recruited to read 32 individual sentences and required to remember the last
      word in each sentence. Target words were presented both in a self-generated and
      provided condition for each participant. Recall and recognition of the words were
      examined immediately, after 30 minutes and after 1 week. RESULTS: Findings
      indicated that both healthy controls and individuals with TBI showed
      significantly better recall and recognition for words in the generated condition
      than words that had been provided to them at immediate, 30-minute and 1-week time
      intervals. CONCLUSION: The self-generation technique effectively improves
      learning and memory in Spanish-speaking individuals with TBI. Results should
      encourage researchers and clinicians to use the principles of cognitive
      psychology to adapt (as opposed to simply translate) cognitive rehabilitation
      protocols for use in Spanish-speaking populations with neurological conditions.

PMID- 22583179
TI  - Late-onset social anxiety disorder following traumatic brain injury.
AB  - BACKGROUND: Neuropsychiatric sequelae are the predominant long-term disability
      after traumatic brain injury (TBI). This study reports a case of late-onset
      social anxiety disorder (SAD) following TBI. CASE REPORT: A patient that was
      spontaneous and extroverted up to 18-years-old started to exhibit significant
      social anxiety symptoms. These symptoms became progressively worse and he sought
      treatment at age 21. He had a previous history of traumatic brain injury (TBI) at
      age 17. Neuroimaging investigations (CT, SPECT and MRI) showed a bony
      protuberance on the left frontal bone, with mass effect on the left frontal lobe.
      He had no neurological signs or symptoms. The patient underwent neurosurgery with
      gross total resection of the lesion and the pathological examination was
      compatible with intradiploic haematoma. CONCLUSIONS: Psychiatric symptoms may be
      the only findings in the initial manifestation of slowly growing extra-axial
      space-occupying lesions that compress the frontal lobe from the outside. Focal
      neurological symptoms may occur only when the lesion becomes large. This case
      report underscores the need for careful exclusion of general medical conditions
      and TBI history in cases of late-onset SAD and may also contribute to the
      elucidation of the neurobiology of this disorder.

PMID- 22583180
TI  - Is high PEEP ventilation strategy safe for acute respiratory distress syndrome
      after severe traumatic brain injury?
AB  - PRIMARY OBJECTIVE: To investigate the safety and efficacy of high positive end
      expiratory pressure (PEEP) ventilation strategy for acute respiratory distress
      syndrome (ARDS) after traumatic brain injury. RESEARCH DESIGN: A case report and
      discussion based on literature review. METHODS AND PROCEDURES: This article
      reports the case of a 17-year-old male patient who developed ARDS after severe
      traumatic brain injury. PEEP was applied and adjusted to appropriate levels on
      the basis of information obtained from continuous monitoring of cerebral and
      systemic haemodynamics. Data from medical charts, surgical notes and radiographic
      findings were reviewed and analysed. MAIN OUTCOMES AND RESULTS: With the
      application of high PEEP ventilation, the patient survived ARDS following severe
      traumatic brain injury and achieved a favourable neurological outcome. A
      titration of PEEP levels from 5-15 cm H2O in the patient resulted in acceptable
      changes of cerebral and systemic haemodynamics, including an increase of
      intracranial pressure (ICP) from 15 to 18 mmHg and a decrease of cerebral
      perfusion pressure (CPP) from 78 to 72 mmHg. CONCLUSIONS: With close monitoring
      of cerebral and systemic haemodynamics, PEEP can be safely applied and titrated
      to an optimal level in the management of ARDS following traumatic brain injury.

PMID- 22583181
TI  - Optic radiation injury in a patient with traumatic brain injury.
AB  - PRIMARY OBJECTIVE: This study reports on a patient who showed an optic radiation
      (OR) injury on diffusion tensor imaging (DTI) following head trauma. The patient,
      who had suffered a traffic accident, underwent conservative management for
      diffuse axonal injury and contusions in the left midbrain, temporal lobe and
      anterior to mid-portion of left OR. He complained of right homonymous hemianopsia
      from the onset of TBI and right bilateral homonymous hemianopsia was detected at
      the 6-month Humphrey visual field test. METHODS AND PROCEDURES: A 20 year-old man
      with traumatic brain injury (TBI) and eight age-matched normal subjects were
      recruited for this study. MAIN OUTCOMES AND RESULTS: The left OR of the patient
      showed a discontinuation around the mid-portion. The FA (fractional anisotropy)
      values of the posterior portions of left OR decreased over two standard
      deviations of normal controls, but the ADC (apparent diffusion coefficient)
      values of these sites increased over two standard deviations of normal controls.
      CONCLUSIONS: Consequently, it was assumed that the main injury site of the left
      OR was located around the posterior portion of the left OR. This results suggest
      that DTI may be a useful technique for detection of an OR injury in patients with
      TBI.

PMID- 22583189
TI  - Elevated circulating levels of YKL-40 are a marker of abnormal glucose tolerance
      in women with polycystic ovary syndrome.
AB  - OBJECTIVE: This study investigates human cartilage glycoprotein-39 (YKL-40)
      levels in patients with polycystic ovary syndrome (PCOS) and controls, and tests
      their relationship with metabolic and hormonal parameters. DESIGN: Clinical study
      carried out in a university hospital in Tekirdag, Turkey. PATIENTS: Eighty-five
      women with PCOS and normal glucose tolerance (NGT) and twenty-five women with
      PCOS and abnormal glucose tolerance (AGT), diagnosed according to Rotterdam
      criteria, and fifty-nine healthy women. MEASUREMENTS: YKL-40 levels, fasting
      hormone levels and metabolic parameters were investigated in all subjects.
      RESULTS: We showed increased YKL-40 levels in women with PCOS compared to
      controls. (152.57 +/- 3.96 MUg/l vs 98.16 +/- 1.6 MUg/l, P < 0.000). YKL
      significantly correlated with BMI (r = 0.344; P < 0.000), 2-h glucose (r = 0.193;
      P = 0.012), HOMA-IR (r = 0.268; P < 0.000) and fasting insulin (r = 0.310; P <
      0.000), but not with waist/hip ratio (r = 0.016; P = 0.832) and fasting glucose
      (r = 0.108; P = 0.832). When ROC curve analysis was used to analyse the
      suitability of YKL-40 to identify glucose intolerance in women with PCOS, area
      under curve for YKL-40 was found to be significant (AGT-PCOS: AUC 0.632, P =
      0.046). CONCLUSION: Plasma YKL-40 levels increased in patients with PCOS compared
      to healthy subjects. Moreover, there was a significant difference in YKL-40
      levels between AGT-PCOS and NGT-PCOS subjects. Subsequently, we also found that
      YKL-40 levels above the cut-off point may help the clinician to predict abnormal
      glucose tolerance in patients with PCOS.

PMID- 22583190
TI  - Effect of alpha-tocopherol on lactone formation in marbled beef and changes in
      lactone volatility during storage.
AB  - Dynamic-headspace sampling with a standard-addition method was employed to
      quantitatively analyze aliphatic lactones in rendered fat from marbled beef and
      to evaluate the effect of the matrix on volatility. Further, the effects of
      different levels of the antioxidant alpha-tocopherol on lactone formation were
      examined. The slopes of the linear regression curves from the standard-addition
      method were significantly changed (P < 0.05 or 0.01) for all lactones after
      storage, with the exception of gamma-octalactone, indicating the volatility of
      the longer-chain lactones were increased after storage. The concentrations of
      gamma-lactones were increased after 7 d of storage at 2  degrees C (P < 0.01),
      and the alpha-tocopherol content in the meat affected the formation of gamma
      octalactone (P < 0.05) and gamma-nonalactone (P < 0.01). The greatest increase
      was observed for gamma-nonalactone in the lowest alpha-tocopherol (2.9 ppm)
      group: the concentration of 51.4 ppb was 11.7-fold higher than that before
      storage. Meanwhile, delta-tetradecalactone in the highest alpha-tocopherol (28.8
      ppm) group showed the highest concentration for the lactones at 415.8 ppb, which
      was 2.6-fold higher than the concentration before storage. The effect of alpha
      tocopherol was unclear for the delta-lactones. The results indicate that most of
      the gamma-lactones are produced by oxidation during storage but that the other
      lactones are also generated by other processes as well.

PMID- 22583191
TI  - Transumbilical portal venous catheterization: a useful adjunct in left lobe
      living donor liver transplantation.
AB  - To improve the processes used for perfusion of the explanted graft and measuring
      the portal venous pressure (PVP) in adult living donor transplantation (LDLT), we
      performed transumbilical portal venous catheterization (TPVC) to reopen the
      umbilical vein and insert the catheter for seven adult patients undergoing left
      lobe LDLT. There were no major complications as a result of this procedure. This
      procedure prior to implanting the graft was derived from our experience and is a
      classic diagnostic technique used during liver surgery. It is a simple and
      effective procedure for perfusion and washout of the graft and for the safe
      monitoring of the intraoperative PVP. We hope that this technique for left lobe
      LDLT will be helpful to others using postoperative PVP monitoring, administration
      of therapeutic drugs through the portal vein, and temporal portal decompression
      by preparation of extracorporeal shunting in patients with a small-for-size
      graft.

PMID- 22583192
TI  - Increased expression of IL-19 in the epithelium of patients with chronic
      rhinosinusitis and nasal polyps.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammation of the nose and of
      the paranasal sinuses. The involvement of the respiratory epithelium in the
      mechanisms of CRS is poorly understood. AIMS: Among proteins expressed by nasal
      epithelial cells in CRS, IL-19 may have key functions. We here aimed to determine
      the expression and regulation of IL-19. METHODS: Nasal biopsies from normal
      subjects (n = 12), subjects with CRS but without nasal polyps (NP) (CRSsNP, n =
      12) and with CRS with NP (CRSwNP, n = 15) were collected. Human Asthma Gene Array
      and real-time PCR were used to evaluate gene expression, western blot analysis
      and immunohistochemistry for protein expression. Results for IL-19 were confirmed
      by real-time PCR. The constitutive and stimulated (LPS, TGF beta) expression of
      IL-19 and cell proliferation were evaluated in a nasal epithelial cell line (RPMI
      2650). RESULTS: Human Asthma Gene Array showed an increased IL-19 gene expression
      in NP from patients with CRS in comparison with normal subjects. Real-time PCR
      confirmed the IL-19 mRNA up-regulation in patients with CRSwNP and showed an up
      regulation of IL-19, at lower extent, in patients with chronic rhinosinusitis
      without nasal polyps (CRSsNP) in comparison with normal subjects. Western blot
      analysis confirmed that IL-19 is increased also at protein level in patients with
      CRSwNP in comparison with normal subjects. In NP, IL-19 is highly expressed in
      the metaplastic nasal epithelium when compared to normal or hyperplastic
      epithelium. LPS stimulation increased IL-19 expression, and recombinant IL-19
      increased cell proliferation in nasal epithelial cells. CONCLUSIONS: IL-19 is
      overexpressed in the epithelium in CRSwNP and increases epithelial cell
      proliferation.

PMID- 22583193
TI  - Breast cancer quality care: what is at stake?

PMID- 22583195
TI  - How should we investigate breast implant rupture?
AB  - We aimed to examine a cohort of patients presenting with breast implant
      complications to establish the sensitivity and specificity of clinical
      examination, Ultrasound Scanning (US) and Magnetic Resonance Imaging (MRI) in the
      diagnosis of implant rupture, and to examine the correlation between US and MRI.
      We performed a 26-month retrospective review. Patients underwent US and MRI to
      exclude rupture. Results of US and MRI were compared prospectively for
      concordance, then retrospectively to clinical findings and surgical diagnosis.
      Thirty-four patients with 60 implants were reviewed. The sensitivities of
      clinical diagnosis, US, and MRI for rupture was 42%, 50%, and 83%, respectively,
      while the specificities were 50%, 90%, and 90%. The concordance between US and
      MRI was 87%. MRI is the investigation of choice for implant rupture. US is a
      valuable alternative with good concordance with MRI. When US is positive for
      implant rupture an MRI is not necessary to confirm the diagnosis. Knowledge of
      the sensitivity and specificity as well as the concordance between the two
      investigations is useful to ensure the appropriate use of available resources.

PMID- 22583194
TI  - Pseudoangiomatous stromal hyperplasia (PASH) of the breast: a series of 24
      patients.
AB  - Pseudoangiomatous stromal hyperplasia (PASH) is a benign mesenchymal
      proliferative lesion of the breast. In 2005, only 109 cases had been reported
      since its initial description in 1986 by Vuitch et al. Our 24 cases represent one
      of the largest series to be reported from a single institution. We
      retrospectively reviewed data from 2004 to 2010 of patients diagnosed with PASH
      by surgical excision or image-guided biopsy. All pathological specimens were
      reviewed by a single pathologist. The samples were stained for estrogen and
      progesterone receptors (ER and PR), CD34, and the lymphatic marker D2-40. All but
      one of 24 (96%) patients presented with breast masses either on imaging or
      clinically. Fourteen of the 24 patients (58%) were diagnosed on surgical
      excision, 10 (42%) diagnosed with core needle biopsy, and five (20%) were
      diagnosed using both techniques. The tumors ranged in size from 0.3 cm to 7.0 cm.
      All women except two were premenopausal or perimenopausal at diagnosis. Nineteen
      samples were available for hormonal receptor staining and of these 18 of 19 (95%)
      were ER or PR positive. PASH was diagnosed in two men, a transgender male on
      hormones and the other with gynecomastia. The patients' ages ranged from 18 to 86
      years old. In addition to PASH other benign histopathological findings include
      stromal fibrosis and atypical ductal or lobular hyperplasia. Imaging revealed no
      distinguishing feature for PASH with benign histology. One patient had
      synchronous ductal carcinoma in-situ (DCIS). Patients were treated with local
      excision or observation. This study suggests that PASH is primarily a diagnosis
      of premenopausal and perimenopausal women. Our series supports a hormonal basis
      for its development due to the positive staining for hormonal receptors.
      Management is conservative surgery for larger masses with careful observation
      being an option in patients not at high risk for breast cancer.

PMID- 22583196
TI  - Dose-dense chemotherapy for breast cancer.
AB  - The concept of dose-dense chemotherapy has emerged and is based on the hypothesis
      that maximal chemotherapy effectiveness can be achieved by scheduling the
      interval of chemotherapy to correspond to the period of most rapid tumor growth,
      as predicted by preclinical models. The granulocyte-colony stimulating factor
      support has permitted the safe delivery of chemotherapy at shorter ("dose-dense")
      inter-treatment intervals. Several randomized trials have been conducted to test
      the feasibility and effectiveness of anthracycline and/or taxanes-based dose
      dense strategies. They have been associated with a modest impact on disease
      recurrence and overall survival of patients with early-stage breast cancer.
      Subset analyses have suggested increased benefits for specific tumor subtypes
      such as hormone receptor-negative, highly proliferative or HER2 overexpressing
      tumors. This review article aims to outline the theoretical framework for dose
      dense chemotherapy and summarizes the results of several recent clinical trials
      addressing this concept within neoadjuvant and adjuvant breast cancer treatment
      and discuss their implications for clinical practice. Further studies are needed
      to define the optimal regimen and the patient population that will receive the
      greatest benefit from dose-dense strategy.

PMID- 22583197
TI  - Invasive micropapillary carcinoma of breast: an under-recognized entity. a series
      of eight cases.
AB  - Invasive micropapillary carcinoma (IMPC) of breast is a morphologically distinct
      and relatively uncommon variant of invasive ductal carcinoma. It is characterized
      by small clusters of tumor cells with surrounding clear stromal spaces; a
      tendency for vascular permeation and therefore, an aggressive clinical course.
      This morphologic pattern can be easily missed especially in a small biopsy
      specimen because pathologists may disregard the clear spaces as artifactual. With
      a tendency of presenting at a higher stage, this morphological pattern needs to
      be mentioned in the histopathology report whenever it is encountered, either in
      its pure form or admixed with conventional ductal carcinoma. We describe eight
      cases of IMPC of breast along with their variable clinical presentations.

PMID- 22583199
TI  - Successful treatment of a two centimeter breast pseudoaneurysm with thrombin
      injection.

PMID- 22583198
TI  - Early stage triple negative and HER2 overexpression breast cancers have similar
      survivals in Chinese patients.

PMID- 22583200
TI  - Identification of an IgE reactive peptide in hen egg riboflavin binding protein
      subjected to simulated gastrointestinal digestion.
AB  - Riboflavin binding protein (RfBP) is a minor protein in hen egg; its potential
      involvement in egg allergy has seldom been studied. The aim of this work was to
      investigate the IgE binding capacity of RfBP before and after simulated
      gastrointestinal digestion. It was shown that digestion of RfBP mainly occurred
      during the gastric phase. The protein fragments resulting from the subsequent
      duodenal phase remained linked through disulfide bonds. Both the intact protein
      and its digests were subjected to inhibition ELISA with sera obtained from
      patients allergic to egg. The results revealed significant IgE binding to intact
      RfBP, whereas the digests showed reduced but substantial IgE binding levels, with
      serum-to-serum variability. The RfBP digests were then subjected to immunoblot
      with allergic patients' sera, and the IgE-reactive peptides were further analyzed
      by MALDI-TOF/TOF mass spectrometry for sequence determination. The RfBP sequence
      41-84 was identified as a novel IgE binding peptide in patients allergic to egg.

PMID- 22583202
TI  - Single-ion heat capacities, C(p)(298)ion, of solids: with a novel route to heat
      capacity estimation of complex anions.
AB  - Single-ion heat capacities, C(p)(298)(ion), are additive values for the
      estimation of room-temperature (298 K) heat capacities of ionic solids. They may
      be used for inferring the heat capacities of ionic solids for which values are
      unavailable and for checking reported values, thus complementing our independent
      method of estimation from formula unit volumes (termed volume-based
      thermodynamics, VBT). Analysis of the reported heat-capacity data presented here
      provides a new self-consistent set of heat capacities for both cations and anions
      that is compatible (and thus may be combined) with an extensive set developed by
      Spencer. The addition of a large range of silicate species permits the estimation
      of the heat capacities of many silicate minerals. The single-ion heat capacities
      of individual silicate anions are observed to be strictly proportional to the
      total number of atoms (Si plus O), n, contained within the silicate anion complex
      itself (e.g., for the anion Si(2)O(7)(2-), n = 9, for SiO(4)(2-), n = 5),
      C(p)(silicate anion)/J K(-1) mol(-1) = 13.8n, in a new rule that is an extension
      of the Neumann-Kopp relationship. The same linear relationship applies to other
      homologous anion series (for example, oxygenated heavy-metal anion complexes such
      as niobates, bismuthates, and tantalates), although with a different
      proportionality constant. A similar proportionality, C(p)(complex anion)/J K(-1)
      mol(-1) ~ 17.5n, which may be regarded as a convenient "rule of thumb", also
      applies, although less strictly, to complex anions in general. The
      proportionality constants reflect the rigidity of the complex anion, being always
      less than the Dulong-Petit value of 25 J K(-1) mol(-1). An emergent feature of
      our VBT and single-ion approaches to an estimation of the thermodynamic
      properties is the identification of anomalies in measured values, as is
      illustrated in this paper.

PMID- 22583203
TI  - Communication: spectroscopic measurement of the binding energy of a carboxylic
      acid-water dimer.
AB  - Infrared-ultraviolet two color pump-probe spectroscopy is used to measure the
      binding energy, D(0,) of a carboxylic acid-water dimer where the acid is 9
      hydroxy-9-fluorenecarboxylic acid. The acid-water configuration presents a
      standard structure for the general acid-water interaction where the water bonds
      to the carboxylic acid group through two intermolecular hydrogen bonds.
      Photodissociation studies with product vibrational state resolution have enabled
      an accurate determination of the binding energy for this acid-water system to be
      D(0) = 2975 +/- 30 cm(-1). Quantum chemical calculations are performed to compare
      with the experimental observations and a recent measurement on the water dimer
      (D(0) = 1105 +/- 10 cm(-1)).

PMID- 22583201
TI  - Characterization of the [2Fe-2S] cluster of Escherichia coli transcription factor
      IscR.
AB  - IscR is an Fe-S cluster-containing transcription factor involved in a homeostatic
      mechanism that controls Fe-S cluster biogenesis in Escherichia coli. Although
      IscR has been proposed to act as a sensor of the cellular demands for Fe-S
      cluster biogenesis, the mechanism by which IscR performs this function is not
      known. In this study, we investigated the biochemical properties of the Fe-S
      cluster of IscR to gain insight into the proposed sensing activity. Mossbauer
      studies revealed that IscR contains predominantly a reduced [2Fe-2S](+) cluster
      in vivo. However, upon anaerobic isolation of IscR, some clusters became oxidized
      to the [2Fe-2S](2+) form. Cluster oxidation did not, however, alter the affinity
      of IscR for its binding site within the iscR promoter in vitro, indicating that
      the cluster oxidation state is not important for regulation of DNA binding.
      Furthermore, characterization of anaerobically isolated IscR using resonance
      Raman, Mossbauer, and nuclear magnetic resonance spectroscopies leads to the
      proposal that the [2Fe-2S] cluster does not have full cysteinyl ligation.
      Mutagenesis studies indicate that, in addition to the three previously identified
      cysteine residues (Cys92, Cys98, and Cys104), the highly conserved His107 residue
      is essential for cluster ligation. Thus, these data suggest that IscR binds the
      cluster with an atypical ligation scheme of three cysteines and one histidine, a
      feature that may be relevant to the proposed function of IscR as a sensor of
      cellular Fe-S cluster status.

PMID- 22583204
TI  - Optimizing transition states via kernel-based machine learning.
AB  - We present a method for optimizing transition state theory dividing surfaces with
      support vector machines. The resulting dividing surfaces require no a priori
      information or intuition about reaction mechanisms. To generate optimal dividing
      surfaces, we apply a cycle of machine-learning and refinement of the surface by
      molecular dynamics sampling. We demonstrate that the machine-learned surfaces
      contain the relevant low-energy saddle points. The mechanisms of reactions may be
      extracted from the machine-learned surfaces in order to identify unexpected
      chemically relevant processes. Furthermore, we show that the machine-learned
      surfaces significantly increase the transmission coefficient for an adatom
      exchange involving many coupled degrees of freedom on a (100) surface when
      compared to a distance-based dividing surface.

PMID- 22583205
TI  - Equation-of-motion coupled-cluster method for ionized states with spin-orbit
      coupling.
AB  - We report implementation of the equation of motion coupled-cluster approach for
      ionized states (EOMIP-CC) with spin-orbit coupling (SOC) using closed-shell state
      as reference in this work. Ionization potentials (IPs) are calculated in the
      ionized 1h and 2h1p space with EOM at the CC singles (CCS) as well as the CC
      singles and doubles levels (CCSD). In this EOMIP-CC approach, SOC is included
      either in both the CC and EOM steps or only in the EOM step. It should be noted
      that IPs provided by the EOMIP-CC approach with SOC included only in the EOM step
      are not size-intensive. Time-reversal symmetry and spatial symmetry are exploited
      for D(2h) and its subgroups to reduce computational effort. All these approaches
      have been shown to be able to afford acceptable estimates for SOC splittings. The
      EOMIP-CCSD with SOC included only in the EOM step can provide reasonable IPs for
      systems containing up to 5th row elements. On the other hand, the EOMIP-CCS
      approach with SOC included in both CC and EOM steps could not predict a bounded
      (2)?(g) (+) state for I(2) (+) and should be used with care.

PMID- 22583206
TI  - Doubly hybrid density functional xDH-PBE0 from a parameter-free global hybrid
      model PBE0.
AB  - Following the XYG3 model which uses orbitals and density from B3LYP, an empirical
      doubly hybrid (DH) functional is developed by using inputs from PBE0. This new
      functional, named xDH-PBE0, has been tested on a number of different molecular
      properties, including atomization energies, bond dissociation enthalpies,
      reaction barrier heights, and nonbonded interactions. From the results obtained,
      xDH-PBE0 not only displays a significant improvement with respect to the parent
      PBE0, but also shows a performance that is comparable to XYG3. Arguably, while
      PBE0 is a parameter-free global hybrid (GH) functional, the B3LYP GH functional
      contains eight fit parameters. From a more general point of view, the present
      work points out that reliable and general-purpose DHs can be obtained with a
      limited number of fit parameters.

PMID- 22583207
TI  - Long range excitonic transport in a biomimetic system inspired by the bacterial
      light-harvesting apparatus.
AB  - Photosynthesis, the process by which energy from sunlight drives cellular
      metabolism, relies on a unique organization of light-harvesting and reaction
      center complexes. Recently, the organization of light-harvesting LH2 complexes
      and dimeric reaction center-light-harvesting I-PufX core complexes in membranes
      of purple non-sulfur bacteria was revealed by atomic force microscopy [S.
      Bahatyrova et al., Nature (London) 430, 1058 (2004)]. Here, we discuss optimal
      exciton transfer in a biomimetic system closely modeled on the structure of LH2
      and its organization within the membrane using a Markovian quantum model with
      dissipation and trapping added phenomenologically. In a deliberate manner, we
      neglect the high level detail of the bacterial light-harvesting complex and its
      interaction with the phonon bath in order to elucidate a set of design principles
      that may be incorporated in artificial pigment-scaffold constructs in a
      supramolecular assembly. We show that our scheme reproduces many of the most
      salient features found in their natural counterpart and may be largely explained
      by simple electrostatic considerations. Most importantly, we show that quantum
      effects act primarily to enforce robustness with respect to spatial and spectral
      disorder between and within complexes. The implications of such an arrangement
      are discussed in the context of biomimetic photosynthetic analogs capable of
      transferring energy efficiently across tens to hundreds of nanometers.

PMID- 22583208
TI  - Discontinuous phase transition in a dimer lattice gas.
AB  - I study a dimer model on the square lattice with nearest neighbor exclusion as
      the only interaction. Detailed simulations using tomographic entropic sampling
      show that as the chemical potential is varied, there is a strongly discontinuous
      phase transition, at which the particle density jumps by about 18% of its maximum
      value, 1/4. The transition is accompanied by the onset of orientational order, to
      an arrangement corresponding to the {1/2, 0, 1/2} structure identified by Phares
      et al. [Physica B 409, 1096 (2011)] in a dimer model with finite repulsion at
      fixed density. Using finite-size scaling and Binder's cumulant, the expected
      scaling behavior at a discontinuous transition is verified in detail. The
      discontinuous transition can be understood qualitatively given that the model
      possesses eight equivalent maximum-density configurations, so that its coarse
      grained description corresponds to that of the q = 8 Potts model.

PMID- 22583209
TI  - Large scale polarizability calculations using the approximate coupled cluster
      model CC2 and MP2 combined with the resolution-of-the-identity approximation.
AB  - We present an implementation of static and frequency-dependent polarizabilities
      for the approximate coupled cluster singles and doubles model CC2 and static
      polarizabilities for second-order Moller-Plesset perturbation theory. Both are
      combined with the resolution-of-the-identity approximation for electron repulsion
      integrals to achieve unprecedented low operation counts, input-output, and disc
      space demands. To avoid the storage of double excitation amplitudes during the
      calculation of derivatives of density matrices, we employ in addition a numerical
      Laplace transformation for orbital energy denominators. It is shown that the
      error introduced by this approximation is negligible already with a small number
      of sampling points. Thereby an implementation of second-order one-particle
      properties is realized, which avoids completely the storage of quantities scaling
      with the fourth power of the system size. The implementation is tested on a set
      of organic molecules including large fused aromatic ring systems and the C(60)
      fullerene. It is demonstrated that exploiting symmetry and shared memory
      parallelization, second-order properties for such systems can be evaluated at the
      CC2 and MP2 level within a few hours of calculation time. As large scale
      applications, we present results for the 7-, 9-, and 11-ring helicenes.

PMID- 22583210
TI  - Convergence of the multipole expansions of the polarization and dispersion
      interactions for atoms under confinement.
AB  - The multipole expansion of the polarization interaction between a charged
      particle and an electrically neutral object has long been known to be asymptotic
      in nature, i.e., the multiple expansion diverges at any finite distance from the
      atom. However, the multipole expansion of the polarization potential of a
      confined hydrogen atom is shown to be absolutely convergent at a distance outside
      the confinement radius, R(0), of the atom. The multipole expansion of the
      dispersion potential between two confined hydrogen atoms is also shown to be
      absolutely convergent provided the two atoms satisfy R > 2R(0), where R is the
      inter-nuclear separation. These results were established analytically using
      oscillator strength sum rules and verified numerically using a B-spline
      description of the hydrogen ground state and its excitation spectrum.

PMID- 22583211
TI  - Experiment and theoretical modeling of the luminescence of silver nanoclusters
      dispersed in oxyfluoride glass.
AB  - Density functional theory (DFT) and complete active space perturbation theory
      (CASPT2) have been applied for modeling the configuration, charge, energy states,
      and spin of luminescent Ag nanoclusters dispersed within the bulk of oxyfluoride
      glass host. The excitation spectra of luminescence of the Ag nanoclusters have
      been measured and simulated by means of the DFT and CASPT2. Electron spin
      resonance spectra have been recorded and suggest diamagnetic state of Ag
      nanoclusters. The silver nanoclusters have been argued to consist mostly of pairs
      of Ag(2) (+) dimers, or Ag(4) (2+) tetramers, with different extent of distortion
      along the tetramer diagonal. The sites for the Ag nanoclusters have been
      suggested where the pairs of Ag ions substitute onto metal and hole cation sites
      and are surrounded by fluorine ions within a fluorite-type lattice.

PMID- 22583212
TI  - Van der Waals interactions in solids using the exchange-hole dipole moment model.
AB  - The exchange-hole dipole moment model of dispersion interactions of Becke and
      Johnson [J. Chem. Phys. 127 154108 (2007)] is implemented for calculations in
      solids using the pseudopotentials/plane-waves approach. The resulting functional
      retains the simplicity and efficiency of semilocal functionals while accurately
      treating dispersion interactions via a semiempirical asymptotic expansion. The
      dispersion coefficients are calculated completely ab initio using local
      quantities alone (density, gradient, Laplacian, and kinetic energy density). The
      two empirical parameters in the damping function are calculated by fit to a 65
      molecule training set recalculated under periodic boundary conditions.
      Calculations in simple solids offer good results with minimal computational cost
      compared to electronic relaxation.

PMID- 22583213
TI  - On the representation of coupled adiabatic potential energy surfaces using quasi
      diabatic Hamiltonians: a distributed origins expansion approach.
AB  - In two previous papers we have introduced a method to generate coupled quasi
      diabatic Hamiltonians (H(d)) that are capable of representing adiabatic energies,
      energy gradients, and derivative couplings over a wide range of geometries
      including seams of conical intersection. In this work, two new synergistic
      features are introduced. Firstly, the functional form of H(d) is generalized.
      Rather than requiring there to be a low energy point of high symmetry to serve as
      the unique origin, functions centered on points distributed in nuclear coordinate
      space are used in the polynomials that comprise the matrix elements in H(d). The
      use of functions with distributed origins, allows reproduction of the ab initio
      data with lower order expansions, and offers the possibility of describing
      multichannel dissociation. The fitting algorithm is combined with a three-step
      procedure in which the domain of H(d) is extended from a core set of nuclear
      configurations to a region of nuclear coordinate space appropriate for nuclear
      dynamics, with a prescribed accuracy. This significant extension of the domain of
      definition compared to our original work, which is facilitated by the distributed
      origin approach, is achieved largely through the use of surface hopping
      trajectories. The 1,2(1)A states of NH(3), which provide an archetypical example
      of nonadiabatic dynamics, are used to demonstrate the utility of this approach.
      The representation describes 21 points on the 1(1)A-2(1)A seam of conical
      intersection and their local topography flawlessly and on the entire domain, the
      electronic structure data is represented to an accuracy of 77.00 (46.90) cm(-1),
      as measured by the root mean square (mean unsigned) error for energies lower than
      50 000 cm(-1). This error is a factor of 10 lower than that of the most accurate
      representation of high quality ab initio data, on a comparable domain, previously
      reported for this system.

PMID- 22583214
TI  - The free energy of expansion and contraction: treatment of arbitrary systems
      using the Jarzynski equality.
AB  - Thermodynamic integration, free energy perturbation, and slow change techniques
      have long been utilised in the calculation of free energy differences between two
      states of a system that has undergone some transformation. With the introduction
      of the Jarzynski equality and the Crooks relation, new approaches are possible.
      This paper investigates an important phenomenon - systems undergoing a change in
      volume/density - and derives both the Jarzynski equality and Crooks relation of
      such systems using a statistical mechanical approach. These results apply to
      systems with arbitrary particle interactions and densities. The application of
      this approach to the expansion/compression of particles confined within a vessel
      with a piston and within a periodic system is considered.

PMID- 22583215
TI  - The role of axis embedding on rigid rotor decomposition analysis of variational
      rovibrational wave functions.
AB  - Approximate rotational characterization of variational rovibrational wave
      functions via the rigid rotor decomposition (RRD) protocol is developed for
      Hamiltonians based on arbitrary sets of internal coordinates and axis embeddings.
      An efficient and general procedure is given that allows employing the Eckart
      embedding with arbitrary polyatomic Hamiltonians through a fully numerical
      approach. RRD tables formed by projecting rotational-vibrational wave functions
      into products of rigid-rotor basis functions and previously determined
      vibrational eigenstates yield rigid-rotor labels for rovibrational eigenstates by
      selecting the largest overlap. Embedding-dependent RRD analyses are performed, up
      to high energies and rotational excitations, for the H(2) (16)O isotopologue of
      the water molecule. Irrespective of the embedding chosen, the RRD procedure
      proves effective in providing unambiguous rotational assignments at low energies
      and J values. Rotational labeling of rovibrational states of H(2) (16)O proves to
      be increasingly difficult beyond about 10,000 cm(-1), close to the barrier to
      linearity of the water molecule. For medium energies and excitations the Eckart
      embedding yields the largest RRD coefficients, thus providing the largest number
      of unambiguous rotational labels.

PMID- 22583216
TI  - Exact expressions for ensemble functionals from particle number dependence.
AB  - Some properties of exact ensemble density functionals can be determined by
      examining the particle number dependence of ground state ensemble density
      matrices for systems where the integer ground state energies satisfy a convexity
      condition. The results include the observation that the integral of the product
      of the functional derivative and Fukui function of functionals that can be
      expressed as the trace of an operator is particle number independent for particle
      numbers between successive integers and the integral itself is equal to the
      difference between functionals evaluated at successive integer particle numbers.
      Expressions that must be satisfied by 2nd and higher order functional derivatives
      are formulated and equations that must be satisfied point by point in space are
      derived. Using the analytic Hooke's atom model, it is shown that commonly used
      correlation functional approximations do not bear any resemblance to a spatially
      dependent expression derived from the exact second order functional derivative of
      the correlation functional. It is also shown that two expressions for the mutual
      Coulomb energy are not equal when approximate exchange and correlation
      functionals are used.

PMID- 22583217
TI  - Multicomponent density functional theory study of the interplay between electron
      electron and electron-proton correlation.
AB  - The interplay between electron-electron and electron-proton correlation is
      investigated within the framework of the nuclear-electronic orbital density
      functional theory (NEO-DFT) approach, which treats electrons and select protons
      quantum mechanically on the same level. Recently two electron-proton correlation
      functionals were developed from the electron-proton pair densities obtained from
      explicitly correlated wavefunctions. In these previous derivations, the kinetic
      energy contribution arising from electron-proton correlation was neglected. In
      this paper, an electron-proton correlation functional that includes this kinetic
      energy contribution is derived using the adiabatic connection formula in
      multicomponent DFT. The performance of the NEO-DFT approach using all three
      electron-proton correlation functionals in conjunction with three well
      established electronic exchange-correlation functionals is assessed. NEO-DFT
      calculations with these electron-proton correlation functionals capture the
      increase in the hydrogen vibrational stretching frequencies arising from the
      inclusion of electron-electron correlation in model systems. Electron-proton and
      electron-electron correlation are found to be uncoupled and predominantly
      additive effects to the total energy for the model systems studied. Thus,
      electron-proton correlation functionals and electronic exchange-correlation
      functionals can be developed independently and subsequently combined together
      without re-parameterization.

PMID- 22583218
TI  - The analysis of NMR J-couplings of saturated and unsaturated compounds by the
      localized second order polarization propagator approach method.
AB  - Calculations of NMR J-coupling with polarization propagators are not invariant
      under unitary transformations at second order level of approach, second order
      polarization propagator approach (SOPPA). They are only invariant at first order
      or random phase level of approach (RPA). We performed "localized" SOPPA (Loc
      SOPPA), calculations of J-couplings applying two different schemes for the
      localization of molecular orbitals(LMO): Foster-Boys and Pipek-Mezey. We show
      here that results of such Loc-SOPPA calculations are different though not much:
      they are less than 6% different in the worst case. Therefore it is possible to
      apply them with confidence in the analysis of the transmission of different
      coupling mechanisms within the molecule. We are able now to get reliable
      information on what LMOs are the most important (and so which are not important)
      for a given J-coupling in a molecule. This information can then be used for
      selecting which are the paths that should be described with the highest possible
      accuracy for that J-coupling calculation. A few unsaturated compounds are
      analyzed: ethene, trans-difluoroethene or DiF-ethene, and imine. It is shown that
      different lone pairs (of p(z) or p(x/y) type) are responsible for the vicinal F-F
      J-coupling in DiF-ethene; and also the fact that the main LP contributor is not
      the same for the fermi contact and the spin-dipolar mechanisms. We also studied
      phosphorous containing compounds such as phosphine and cis-propylene phosphine.
      In both cases the analysis of the main LMO contributing to one-bond P-H coupling
      and through-space P-C coupling were performed. The above mentioned unsaturated
      molecular systems have quasiinstability problems that arise at RPA level of
      approach. We show here that they are mostly originated in the antibonding pi*
      LMO, corresponding to the C=C or C=N double bonds. We performed the analysis of
      the origin of quasiinstabilities for the SD mechanism. The contribution of each
      kind of excitation terms to SOPPA calculations were considered, meaning the main
      contributions by single and double excitations. It is shown that one can get more
      than 97% of the total electron correlation contribution when including terms that
      mainly contain single excitations (though double-excitation matrix elements
      should still be calculated).

PMID- 22583219
TI  - The extended Koopmans' theorem: vertical ionization potentials from natural
      orbital functional theory.
AB  - The Piris natural orbital functional, PNOF5, has been used to predict vertical
      ionization potentials of a selected set of 30 organic and inorganic spin
      compensated molecules by means of the extended Koopmans' theorem. Electron
      affinities of 10 selected radicals have also been estimated as the inverse of the
      ionization potentials of the anionic species, calculated at the experimental
      geometries of the neutral radicals. The basis set limit effects have been
      assessed by inspecting the data obtained for the Dunning's basis set series cc
      pVXZ and aug-cc-pVXZ (X = D, T, Q, 5). The performance of the PNOF5 is
      established by carrying out a statistical analysis of the mean absolute errors
      (MAEs) with respect to the experiment values. The calculated PNOF5 ionization
      potentials and electron affinities agree satisfactorily with the corresponding
      experimental data, with MAEs smaller than 0.5 eV.

PMID- 22583220
TI  - Two-dimensional stimulated resonance Raman spectroscopy of molecules with
      broadband x-ray pulses.
AB  - Expressions for the two-dimensional stimulated x-ray Raman spectroscopy (2D-SXRS)
      signal obtained using attosecond x-ray pulses are derived. The 1D- and 2D-SXRS
      signals are calculated for trans-N-methyl acetamide (NMA) with broad bandwidth
      (181 as, 14.2 eV FWHM) pulses tuned to the oxygen and nitrogen K-edges.
      Crosspeaks in 2D signals reveal electronic Franck-Condon overlaps between valence
      orbitals and relaxed orbitals in the presence of the core-hole.

PMID- 22583221
TI  - Non-stationary forward flux sampling.
AB  - We present a method, Non-Stationary Forward Flux Sampling, that allows efficient
      simulation of rare events in both stationary and non-stationary stochastic
      systems. The method uses stochastic branching and pruning to achieve uniform
      sampling of trajectories in phase space and time, leading to accurate estimates
      for time-dependent switching propensities and time-dependent phase space
      probability densities. It is suitable for equilibrium or non-equilibrium systems,
      in or out of stationary state, including non-Markovian or externally driven
      systems. We demonstrate the validity of the technique by applying it to a one
      dimensional barrier crossing problem that can be solved exactly, and show its
      usefulness by applying it to the time-dependent switching of a genetic toggle
      switch.

PMID- 22583222
TI  - Rare switching events in non-stationary systems.
AB  - Physical systems with many degrees of freedom can often be understood in terms of
      transitions between a small number of metastable states. For time-homogeneous
      systems with short-term memory these transitions are fully characterized by a set
      of rate constants. We consider the question how to extend such a coarse-grained
      description to non-stationary systems and to systems with finite memory. We
      identify the physical regimes in which time-dependent rates are meaningful, and
      state microscopic expressions that can be used to measure both externally time
      dependent and history-dependent rates in microscopic simulations. Our description
      can be used to generalize Markov state models to time-dependent Markovian or non
      Markovian systems.

PMID- 22583223
TI  - Synergetic effects of double laser pulses for the formation of mild plasma in
      water: toward non-gated underwater laser-induced breakdown spectroscopy.
AB  - We experimentally study the dynamics of the plasma induced by the double-laser
      pulse irradiation of solid target in water, and find that an appropriate choice
      of the pulse energies and pulse interval results in the production of an
      unprecedentedly mild (low-density) plasma, the emission spectra of which are very
      narrow even without the time-gated detection. The optimum pulse interval and
      pulse energies are 15-30 MUs and about ~1 mJ, respectively, where the latter
      values are much smaller than those typically employed for this kind of study. In
      order to clarify the mechanism for the formation of mild plasma we examine the
      role of the first and second laser pulses, and find that the first pulse produces
      the cavitation bubble without emission (and hence plasma), and the second pulse
      induces the mild plasma in the cavitation bubble. These findings may present a
      new phase of underwater laser-induced breakdown spectroscopy.

PMID- 22583224
TI  - Torsion-wagging tunneling and vibrational states in hydrazine determined from its
      ab initio potential energy surface.
AB  - Geometries, anharmonic vibrations, and torsion-wagging (TW) multiplets of
      hydrazine and its deuterated species are studied using high-level ab initio
      methods employing the second-order Moller-Plesset perturbation theory (MP2) as
      well as the coupled cluster singles and doubles model including connected triple
      corrections, CCSD(T), in conjunction with extended basis sets containing diffuse
      and core functions. To describe the splitting patterns caused by tunneling in TW
      states, the 3D potential energy surface (PES) for the large-amplitude TW modes is
      constructed. Stationary points in the 3D PES, including equivalent local minima
      and saddle points are characterized. Using this 3D PES, a flexible Hamiltonian is
      built numerically and then employed to solve the vibrational problem for TW
      coupled motion. The calculated ground state r(av) structure is expected to be
      more reliable than the experimental one that has been determined using a
      simplified structural model. The calculated fundamental frequencies allowed
      resolution of the assignment problems discussed earlier in the literature. The
      determined energy barriers, including the contributions from the small-amplitude
      vibrations, to the tunneling of the symmetric and antisymmetric wagging mode of
      1997 cm(-1) and 3454 cm(-1), respectively, are in reasonable agreement with the
      empirical estimates of 2072 cm(-1) and 3312 cm(-1), respectively [W. Lodyga et
      al. J. Mol. Spectrosc. 183, 374 (1997)]. However, the empirical torsion barrier
      of 934 cm(-1) appears to be overestimated. The ab initio calculations yield two
      torsion barriers: cis and trans of 744 cm(-1) and 2706 cm(-1), respectively. The
      multiplets of the excited torsion states are predicted from the refined 3D PES.

PMID- 22583225
TI  - Mimicking trimeric interactions in the aromatic side chains of the proteins: a
      gas phase study of indole...(pyrrole)2 heterotrimer.
AB  - Aromatic trimeric interactions are extremely significant in the stabilization of
      the specific structures of the proteins as well as protein-protein, and protein
      ligand interactions. Here we have reported a direct evidence of the observation
      of a cyclic asymmetric structure of indole...(pyrrole)(2) trimer bound by three N
      H...pi hydrogen bonding interactions in a supersonic jet. The experiment has been
      performed by using resonant two-photon ionization (R2PI), IR-UV, and UV-UV double
      resonance spectroscopic techniques. Density functional theory (DFT) calculations
      nicely corroborate the experimental results showing one weakly allowed IR-active
      band due to symmetric stretch of the N-H bonds and two strongly allowed IR-active
      bands due to two types of asymmetric stretches of the N-H bonds in the trimer.
      The present spectroscopic investigation demonstrates that the strength of the
      three N-H...pi bound intermolecular interactions in the cyclic asymmetric trimer
      is quite different unlike the corresponding interactions of similar strength in a
      cyclic symmetric trimer.

PMID- 22583226
TI  - A theoretical investigation of the feasibility of Tannor-Rice type control:
      application to selective bond breakage in gas-phase dihalomethanes.
AB  - Within the B absorption band of CH(2)BrCl, we theoretically analyze the laser
      induced control of the Br/Cl branching ratio, Br + CH(2)Cl <- CH(2)BrCl ->
      CH(2)Br + Cl, with CH(2)BrCl initially in its vibrational ground state. For weak
      field excitation, the Br/Cl branching ratio increases as a function of
      wavelength, however, for wavelengths below 180 nm the branching ratio cannot be
      made smaller than 0.4. Using optimal control theory, we show that the branching
      ratio can be made significantly less than 0.4, only when very strong fields are
      employed. Thus, the present work strongly suggests that a Tannor-Rice type laser
      control mechanism for selective bond breakage in CH(2)BrCl cannot take place
      without accompanying photoionization.

PMID- 22583227
TI  - State-dependent photoionization cross-sections of 3d transition metal atoms.
AB  - Using the saturation method, we measured the absolute photoionization cross
      sections of several excited states of titanium, vanadium, chromium, iron, and
      cobalt. These results are reported for the first time in this paper. The measured
      values range from 0.4 +/- 0.1 Mb to 6.9 +/- 2.0 Mb. The results show that the
      photoionization cross-section depends on the atomic state and not just on the
      electronic configuration.

PMID- 22583228
TI  - Raman spectra of vibrational and librational modes in methane clathrate hydrates
      using density functional theory.
AB  - The sI type methane clathrate hydrate lattice is formed during the process of
      nucleation where methane gas molecules are encapsulated in the form of
      dodecahedron (5(12)CH(4)) and tetrakaidecahedron (5(12)6(2)CH(4)) water cages.
      The characterization of change in the vibrational modes which occur on the
      encapsulation of CH(4) in these cages plays a key role in understanding the
      formation of these cages and subsequent growth to form the hydrate lattice. In
      this present work, we have chosen the density functional theory (DFT) using the
      dispersion corrected B97-D functional to characterize the Raman frequency
      vibrational modes of CH(4) and surrounding water molecules in these cages. The
      symmetric and asymmetric C-H stretch in the 5(12)CH(4) cage is found to shift to
      higher frequency due to dispersion interaction of the encapsulated CH(4) molecule
      with the water molecules of the cages. However, the symmetric and asymmetric O-H
      stretch of water molecules in 5(12)CH(4) and 5(12)6(2)CH(4) cages are shifted
      towards lower frequency due to hydrogen bonding, and interactions with the
      encapsulated CH(4) molecules. The CH(4) bending modes in the 5(12)CH(4) and
      5(12)6(2)CH(4) cages are blueshifted, though the magnitude of the shifts is lower
      compared to modes in the high frequency region which suggests bending modes are
      less affected on encapsulation of CH(4). The low frequency librational modes
      which are collective motion of the water molecules and CH(4) in these cages show
      a broad range of frequencies which suggests that these modes largely contribute
      to the formation of the hydrate lattice.

PMID- 22583229
TI  - Spectroscopic identification of benzyl-type radicals generated by corona
      discharge of 2-chloro-4-fluorotoluene.
AB  - By means of a technique of corona excited supersonic expansion coupled with a
      pinhole-type glass nozzle, we generated vibronically excited but jet-cooled
      benzyl-type radicals from precursor 2-chloro-4-fluorotoluene seeded in a large
      amount of inert carrier gas He. From an analysis of the visible vibronic emission
      spectrum, we found evidence of the formation of the 2-chloro-4-fluorobenzyl and 4
      fluorobenzyl radicals. A possible pathway for the formation of these benzyl-type
      radicals is herein proposed. Also, the electronic energy in the D(1) -> D(0)
      transition and the vibrational mode frequencies of the 2-chloro-4-fluorobenzyl
      radical in the ground electronic state were accurately determined, for the first
      time, by comparison with ab initio calculations and the known vibrational data of
      the precursor.

PMID- 22583230
TI  - Full dimension Rb2He ground triplet potential energy surface and quantum
      scattering calculations.
AB  - We have developed a three-dimensional potential energy surface for the lowest
      triplet state of the Rb(2)He complex. A global analytic fit is provided as in the
      supplementary material [see supplementary material at
      http://dx.doi.org/10.1063/1.4709433 for the corresponding Fortran code]. This
      surface is used to perform quantum scattering calculations of (4)He and (3)He
      colliding with (87)Rb(2) in the partial wave J = 0 at low and ultralow energies.
      For the heavier helium isotope, the computed vibrational relaxation probabilities
      show a broad and strong shape resonance for a collisional energy of 0.15 K and a
      narrow Feshbach resonance at about 17 K for all initial Rb(2) vibrational states
      studied. The broad resonance corresponds to an efficient relaxation mechanism
      that does not occur when (3)He is the colliding partner. The Feshbach resonance
      observed at higher collisional energy is robust with respect to the isotopic
      substitution. However, its effect on the vibrational relaxation mechanism is
      faint for both isotopes.

PMID- 22583231
TI  - Vibrational quenching of excitonic splittings in H-bonded molecular dimers: the
      electronic Davydov splittings cannot match experiment.
AB  - The S(1)/S(2) state exciton splittings of symmetric doubly hydrogen-bonded gas
      phase dimers provide spectroscopic benchmarks for the excited-state electronic
      couplings between UV chromophores. These have important implications for
      electronic energy transfer in multichromophoric systems ranging from
      photosynthetic light-harvesting antennae to photosynthetic reaction centers,
      conjugated polymers, molecular crystals, and nucleic acids. We provide laser
      spectroscopic data on the S(1)/S(2) excitonic splitting Delta(exp) of the doubly
      H-bonded o-cyanophenol (oCP) dimer and compare to the splittings of the dimers of
      (2-aminopyridine)(2), [(2AP)(2)], (2-pyridone)(2), [(2PY)(2)], (benzoic acid)(2),
      [(BZA)(2)], and (benzonitrile)(2), [(BN)(2)]. The experimental S(1)/S(2)
      excitonic splittings are Delta(exp) = 16.4 cm(-1) for (oCP)(2), 11.5 cm(-1) for
      (2AP)(2), 43.5 cm(-1) for (2PY)(2), and <1 cm(-1) for (BZA)(2). In contrast, the
      vertical S(1)/S(2) energy gaps Delta(calc) calculated by the approximate second
      order coupled cluster (CC2) method for the same dimers are 10-40 times larger
      than the Delta(exp) values. The qualitative failure of this and other ab initio
      methods to reproduce the exciton splitting Delta(exp) arises from the Born
      Oppenheimer (BO) approximation, which implicitly assumes the strong-coupling case
      and cannot be employed to evaluate excitonic splittings of systems that are in
      the weak-coupling limit. Given typical H-bond distances and oscillator strengths,
      the majority of H-bonded dimers lie in the weak-coupling limit. In this case, the
      monomer electronic-vibrational coupling upon electronic excitation must be
      accounted for; the excitonic splittings arise between the vibronic (and not the
      electronic) transitions. The discrepancy between the BO-based splittings
      Delta(calc) and the much smaller experimental Delta(exp) values is resolved by
      taking into account the quenching of the BO splitting by the intramolecular
      vibronic coupling in the monomer S(1) <- S(0) excitation. The vibrational
      quenching factors Gamma for the five dimers (oCP)(2), (2AP)(2), (2AP)(2),
      (BN)(2), and (BZA)(2) lie in the range Gamma = 0.03-0.2. The quenched excitonic
      splittings Gamma[middle dot]Delta(calc) are found to be in very good agreement
      with the observed splittings Delta(exp). The vibrational quenching approach
      predicts reliable Delta(exp) values for the investigated dimers, confirms the
      importance of vibrational quenching of the electronic Davydov splittings, and
      provides a sound basis for predicting realistic exciton splittings in
      multichromophoric systems.

PMID- 22583232
TI  - Ab initio calculation of the rotational spectrum of methane vibrational ground
      state.
AB  - In a previous article we have introduced an alternative perturbation scheme to
      the traditional one starting from the harmonic oscillator, rigid rotator
      Hamiltonian, to find approximate solutions of the spectral problem for rotation
      vibration molecular Hamiltonians. The convergence of our method for the methane
      vibrational ground state rotational energy levels was quicker than that of the
      traditional method, as expected, and our predictions were quantitative. In this
      second article, we study the convergence of the ab initio calculation of
      effective dipole moments for methane within the same theoretical frame. The first
      order of perturbation when applied to the electric dipole moment operator of a
      spherical top gives the expression used in previous spectroscopic studies. Higher
      orders of perturbation give corrections corresponding to higher centrifugal
      distortion contributions and are calculated accurately for the first time. Two
      potential energy surfaces of the literature have been used for solving the
      anharmonic vibrational problem by means of the vibrational mean field
      configuration interaction approach. Two corresponding dipole moment surfaces were
      calculated in this work at a high level of theory. The predicted intensities
      agree better with recent experimental values than their empirical fit. This
      suggests that our ab initio dipole moment surface and effective dipole moment
      operator are both highly accurate.

PMID- 22583233
TI  - Importance of semicore states in GW calculations for simulating accurately the
      photoemission spectra of metal phthalocyanine molecules.
AB  - The quasi-particle energy levels of the Zn-Phthalocyanine (ZnPc) molecule
      calculated with the GW approximation are shown to depend sensitively on the
      explicit description of the metal-center semicore states. We find that the
      calculated GW energy levels are in good agreement with the measured experimental
      photoemission spectra only when explicitly including the Zn 3s and 3p semicore
      states in the valence. The main origin of this effect is traced back to the
      exchange term in the self-energy GW approximation. Based on this finding, we
      propose a simplified approach for correcting GW calculations of metal
      phthalocyanine molecules that avoids the time-consuming explicit treatment of the
      metal semicore states. Our method allows for speeding up the calculations without
      compromising the accuracy of the computed spectra.

PMID- 22583234
TI  - Microwave spectroscopy of platinum monofluoride and platinum monochloride in the
      X 2Pi(3/2) states.
AB  - Platinum monofluoride (PtF) and platinum monochloride (PtCl) were detected in the
      gas phase using a source-modulated microwave spectrometer. The PtF and PtCl
      radicals were generated in a free space cell using the sputtering reaction from a
      platinum sheet placed on the inner surface of a stainless steel cathode through a
      dc glow discharge plasma of CF(4) and Cl(2), respectively, diluted with Ar.
      Rotational transitions were measured in the region between 150 and 313 GHz.
      Rotational, centrifugal distortion, and several fine- and hyperfine-structure
      constants were determined by a least-squares analysis. The observed fine
      structure spectral patterns indicate that both PtF and PtCl radicals have the
      (2)Pi(3/2) electronic ground states, while the related cyanide PtCN and hydride
      PtH radicals have the (2)Delta(5/2) electronic ground states.

PMID- 22583235
TI  - Theoretical analysis of photoinduced H-atom elimination in thiophenol.
AB  - The photoinduced hydrogen elimination reaction in thiophenol via the conical
      intersections of the dissociative (1)pisigma* excited state with the bound
      (1)pipi* excited state and the electronic ground state has been investigated with
      ab initio electronic-structure calculations and time-dependent quantum wave
      packet calculations. A screening of the coupling constants of the symmetry
      allowed coupling modes at the (1)pipi*-(1)pisigma* and (1)pisigma*-S(0) conical
      intersection shows that the SH torsional mode is by far the most important
      coupling mode at both conical intersections. A model including three intersecting
      potential-energy surfaces (S(0), (1)pipi*, (1)pisigma*) and two nuclear degrees
      of freedom (SH stretch and SH torsion) has been constructed on the basis of ab
      initio complete-active-space self-consistent field and multireference second
      order perturbation theory calculations. The nonadiabatic quantum wave-packet
      dynamics initiated by optical excitation of the (1)pipi* and (1)pisigma* states
      has been explored for this three-state two-coordinate model. The
      photodissociation dynamics is characterized in terms of snapshots of time
      dependent wave packets, time-dependent electronic population probabilities, and
      the branching ratio of the (2)sigma/(2)pi electronic states of the thiophenoxyl
      radical. The dependence of the timescale of the photodissociation process and the
      branching ratio on the initial excitation of the SH stretching and SH torsional
      vibrations has been analyzed. It is shown that the node structure, which is
      imposed on the nuclear wave packets by the initial vibrational preparation as
      well as by the transitions through the conical intersections, has a profound
      effect on the photodissociation dynamics. The effect of additional weak coupling
      modes of CC twist (nu(16a)) and ring-distortion (nu(16b)) character has been
      investigated with three-dimensional and four-dimensional time-dependent wave
      packet calculations, and has been found to be minor.

PMID- 22583236
TI  - Quantum dynamics of H + LiH reaction and its isotopic variants.
AB  - Time-dependent quantum wave packet dynamics study is carried out to investigate
      the initial state selected channel specific reactivity of H + LiH collisional
      system on a new and more accurate ab initio potential energy surface developed by
      Wernli et al. [J. Phys. Chem. A 113, 1121 (2009)]. The H + LiH reaction proceeds
      through LiH depletion and H-exchange paths. While the former path is highly
      exoergic (by ~2.258 eV), the latter path is thermoneutral. State selected and
      energy resolved integral reaction cross sections and thermal rate constants are
      reported and compared with the literature data. The reactivity of the LiH
      depletion channel is found to be greater than the H-exchange channel. Rotational
      excitation of the reagent LiH molecule causes a decrease of reactivity of both
      the channels. On the other hand, the vibrational excitation of the reagent LiH
      decreases the reactivity of the LiH depletion channel and increases the
      reactivity of the H-exchange channel. The effect of isotopic substitution (H by
      D) on the reaction dynamics is also examined.

PMID- 22583237
TI  - Insight into the vertical detachment energy oscillation of Na(n)C60(-) clusters.
AB  - We have performed a detailed density functional theory study on the structural
      and electronic properties of Na(n)C(60)(-) (n = 1-12) clusters. The calculated
      vertical detachment energies show good agreement with the experimental data,
      which confirms the 3p (n = 3p) oscillation rule. The oscillation can be
      attributed to the combination of the charge depletion distribution induced by
      removing electrons and the number of the sodium atoms in direct contact with the
      fullerene. Based on the structural and electronic properties, the Na atoms can be
      categorized into two groups, one is for the metal atoms directly bonded to the
      fullerene surface, and the other one is for those without bonding to the
      fullerene. The Na atoms in group one would donate electrons to both the fullerene
      and the Na atoms in group two. As the total number of the sodium atoms increases,
      the number of Na atoms in group one would continue increasing till the size n =
      3p - 1 to meet a shoulder from n = 3p - 1 to n = 3p, which accounts for the
      maximum vertical detachment energy at the size of n = 3p as drawn from the
      detailed electronic property studies.

PMID- 22583238
TI  - Effect of Coulomb interactions on the vibronic couplings in C60(-).
AB  - Vibronic couplings in C(60)(-) anion are discussed on the basis of the concept of
      the vibronic coupling density (VCD) [T. Sato, K. Tokunaga, and K. Tanaka, J.
      Chem. Phys. 124, 024314 (2006); K. Tokunaga, T. Sato, and K. Tanaka, J. Chem.
      Phys. 124, 154303 (2006); and T. Sato, K. Tokunaga, and K. Tanaka, J. Phys. Chem.
      A 112, 758 (2008)]. The VCD analysis clearly reveals that the coupling to the
      bending h(g)(2) mode is weaker than the coupling to the stretching h(g)(7) and
      h(g)(8) modes. For the vibronic couplings with the stretching modes,
      polarizations of the electron density difference on the bonds play a crucial role
      in the vibronic couplings. Such a polarized electron density difference appears
      as a result of the Coulomb interactions between the electrons in the lowest
      unoccupied molecular orbital and relevant doubly-occupied orbitals.

PMID- 22583239
TI  - Accurate ab initio potential energy surfaces for the 3A'' and 3A' electronic
      states of the O(3P)+HBr system.
AB  - In this work, we report the construction of potential energy surfaces for the
      (3)A('') and (3)A(') states of the system O((3)P) + HBr. These surfaces are based
      on extensive ab initio calculations employing the MRCI+Q/CBS+SO level of theory.
      The complete basis set energies were estimated from extrapolation of MRCI+Q/aug
      cc-VnZ(-PP) (n = Q, 5) results and corrections due to spin-orbit effects obtained
      at the CASSCF/aug-cc-pVTZ(-PP) level of theory. These energies, calculated over a
      region of the configuration space relevant to the study of the reaction O((3)P) +
      HBr -> OH + Br, were used to generate functions based on the many-body expansion.
      The three-body potentials were interpolated using the reproducing kernel Hilbert
      space method. The resulting surface for the (3)A('') electronic state contains
      van der Waals minima on the entrance and exit channels and a transition state
      6.55 kcal/mol higher than the reactants. This barrier height was then scaled to
      reproduce the value of 5.01 kcal/mol, which was estimated from coupled cluster
      benchmark calculations performed to include high-order and core-valence
      correlation, as well as scalar relativistic effects. The (3)A(') surface was also
      scaled, based on the fact that in the collinear saddle point geometry these two
      electronic states are degenerate. The vibrationally adiabatic barrier heights are
      3.44 kcal/mol for the (3)A('') and 4.16 kcal/mol for the (3)A(') state.

PMID- 22583240
TI  - Observation of infrared free-induction decay and optical nutation signals from
      nitrous oxide using a current modulated quantum cascade laser.
AB  - Free induction decay (FID), optical nutation, and rapid passage induced signals
      in nitrous oxide, under both optically thin and optically thick conditions, have
      been observed using a rapid current pulse modulation, or chirp, applied to the
      slow current ramp of a quantum cascade (QC) laser. The variation in optical depth
      was achieved by increasing the pressure of nitrous oxide in a long path length
      multipass absorption cell. This allows the variation of optical depth to be
      achieved over a range of low gas pressures. Since, even at the highest gas
      pressure used in the cell, the chirp rate of the QC laser is faster than the
      collisional reorientation time of the molecules, there is minimal collisional
      damping, allowing a large macroscopic polarization of the molecular dipoles to
      develop. This is referred to as rapid passage induced polarization. The resultant
      FID signals are enhanced due to the constructive interference between the field
      within the gas generated by the slow ramp of the laser (pump), and that of the
      fast chirp of the laser (probe) signal generated by pulse modulation of the
      continuously operating QC laser. The FID signals obtained at large optical depth
      have not been observed previously in the mid-infrared regions, and unusual
      oscillatory signals have been observed at the highest gas pressures used.

PMID- 22583241
TI  - The ac Stark effect in nitric oxide induced by rapidly swept continuous wave
      quantum cascade lasers.
AB  - A large ac Stark effect has been observed when nitric oxide, at low pressure in a
      long optical path (100 m) Herriot cell, is subjected to infrared radiation from a
      rapidly swept, continuous wave infrared quantum cascade laser. As the frequency
      sweep rate of the laser is increased, an emission signal induced by rapid passage
      occurs after the laser frequency has passed through the resonance of 1-0
      R(11.5)(3/2 /)molecular absorption line. At very high sweep rates a laser field
      induced splitting of the absorptive part of the signal is observed, due to the ac
      Stark effect. This splitting is related to the Autler-Townes mixing of the e, f
      lambda doublet components of the 1-0 R(11.5)(3/2) transition, which lie under the
      Doppler broadened envelope.

PMID- 22583242
TI  - Sub-Doppler spectra of infrared hyperfine transitions of nitric oxide using a
      pulse modulated quantum cascade laser: rapid passage, free induction decay, and
      the ac Stark effect.
AB  - Using a low power, rapid (nsec) pulse-modulated quantum cascade (QC) laser,
      collective coherent effects in the 5 MUm spectrum of nitric oxide have been
      demonstrated by the observation of sub-Doppler hyperfine splitting and also
      Autler-Townes splitting of Doppler broadened lines. For nitrous oxide,
      experiments and model calculations have demonstrated that two main effects occur
      with pulse-modulated (chirped) quantum cascade lasers: free induction decay
      signals, and signals induced by rapid passage during the laser chirp. In the open
      shell molecule, NO, in which both Lambda-doubling splitting and hyperfine
      structure occur, laser field-induced coupling between the hyperfine levels of the
      two Lambda-doublet components can induce a large ac Stark effect. This may be
      observed as sub-Doppler structure, field-induced splittings, or Autler-Townes
      splitting of a Doppler broadened line. These represent an extension of the types
      of behaviour observed in the closed shell molecule nitrous oxide, using the same
      apparatus, when probed with an 8 MUm QC laser.

PMID- 22583243
TI  - Electronic spectroscopy of I(2)-Xe complexes in solid Krypton.
AB  - In the present work, we have studied ion-pair states of matrix-isolated I(2) with
      vacuum-UV absorption and UV-vis-NIR emission, where the matrix environment is
      systematically changed by mixing Kr with Xe, from pure Kr to a more polarizable
      Xe host. Particular emphasis is put on low doping levels of Xe that yield a
      binary complex I(2)-Xe, as verified by coherent anti-Stokes Raman scattering
      (CARS) measurements. Associated with interaction of I(2) with Xe we can observe
      strong new absorption in vacuum-UV, redshifted 2400 cm(-1) from the X -> D
      transition of I(2). Observed redshift can be explained by symmetry breaking of
      ion-pair states within the I(2)-Xe complex. Systematic Xe doping of Kr matrices
      shows that at low doping levels, positions of I(2) ion-pair emissions are not
      significantly affected by complexation with Xe, but simultaneous increase of
      emissions from doubly spin-excited states indicates non-radiative relaxation to
      valence states. At intermediate doping levels ion-pair emissions shift
      systematically to red due to change in the average polarizability of the
      environment. We have conducted spectrally resolved ultrafast pump-probe ion-pair
      emission studies with pure and Xe doped Kr matrices, in order to reveal the
      influence of Xe to I(2) dynamics in solid Kr. Strikingly, relaxed emission from
      the ion-pair states shows no indication of complex presence. It further indicates
      that the complex escapes detection due to a non-radiative relaxation.

PMID- 22583244
TI  - Determination of the solid-fluid coexistence of the n - 6 Lennard-Jones system
      from free energy calculations.
AB  - The solid-fluid coexistence properties of the n - 6 Lennard-Jones system, n from
      7 to 12, are reported. The procedure relies on determining Helmholtz free energy
      curves as a function of volume for each phase independently, from several NVT
      simulations, and then connecting it to points of known absolute free energy. For
      n = 12 this requires connecting the simulated points to states of very low
      densities on the liquid phase, and to a harmonic crystal for the solid phase,
      which involves many extra simulations for each temperature. For the reference
      points of the remaining systems, however, the free energy at a given density and
      temperature can be calculated relative to the n = 12 system. The method presented
      here involves a generalization of the multiple histogram method to combine
      simulations performed with different potentials, provided they visit overlapping
      regions of the phase space, and allows for a precise calculation of relative free
      energies. The densities, free energies, average potential energies, pressure, and
      chemical potential at coexistence are presented for up to T* = 5.0 and new
      estimations of the triple points are given for the n - 6 Lennard-Jones system.

PMID- 22583245
TI  - Medium decoupling of dynamics at temperatures ~100 K above glass-transition
      temperature: a case study with (acetamide + lithium bromide/nitrate) melts.
AB  - Time-resolved fluorescence Stokes shift and anisotropy measurements using a
      solvation probe in [0.78CH(3)CONH(2) + 0.22{f LiBr + (1-f) LiNO(3)}] melts reveal
      a strong decoupling of medium dynamics from viscosity. Interestingly, this
      decoupling has been found to occur at temperatures ~50-100 K above the glass
      transition temperatures of the above melt at various anion concentrations
      (f(LiBr)). The decoupling is reflected via the following fractional viscosity
      dependence (eta) of the measured average solvation and rotation times (<tau(s)>
      and <tau(r)>, respectively): <tau(x)> ? (eta/T)(p) (x being solvation or
      rotation), with p covering the range, 0.20 < p < 0.70. Although this is very
      similar to what is known for deeply supercooled liquids, it is very surprising
      because of the temperature range at which the above decoupling occurs for these
      molten mixtures. The kinship to the supercooled liquids is further exhibited via
      p which is always larger for <tau(r)> than for <tau(s)>, indicating a sort of
      translation-rotation decoupling. Multiple probes have been used in steady state
      fluorescence measurements to explore the extent of static heterogeneity.
      Estimated experimental dynamic Stokes shift for coumarin 153 in these mixtures
      lies in the range, 1000 < Deltanu(t)/cm(-1) < 1700, and is in semi-quantitative
      agreement with predictions from our semi-molecular theory. The participation of
      the fluctuating density modes at various length-scales to the observed solvation
      times has also been investigated.

PMID- 22583246
TI  - Vibrational modes of hydrogens in the proton ordered phase XI of ice: Raman
      spectra above 400 cm(-1).
AB  - Polarized Raman spectra of the proton ordered phase of ice Ih, i.e., ice XI, were
      measured above 400 cm(-1) in the range of librational, bending, and stretching
      vibrations. Vibrational modes in ice XI, of which symmetry is C(2v)
      (12)(Cmc2(1)), were discussed from the group theoretical point of view. In the
      librational mode spectra below 1200 cm(-1), several new peaks and clear
      polarization dependencies were observed. Assignments of the librational modes
      agree reasonably well with the recent MD calculations by Iwano et al. (J. Phys.
      Soc. Jpn. 79, 063601 (2010)). In contrast, the spectra for bands above 1200 cm(
      1) show no distinct polarization dependencies and the spectra resemble those in
      ice Ih. In ice XI, however, fine structure composed of several weak peaks appear
      on the broad bending and the combination band. No direct evidence of the LO-TO
      splitting of the nu(3) anti-symmetric stretching mode was obtained. It is
      contrary to the case of the translational modes Abe and Shigenari (J. Chem. Phys.
      134, 104506 (2011)). Present results suggest that the influence of the proton
      ordering in ice XI is weaker than the effect of inter- and intra-molecular
      couplings in the stretching vibrations of ice Ih.

PMID- 22583247
TI  - Dissipative geometric phase and decoherence in parity-violating chiral molecules.
AB  - Within a generalized Langevin framework for open quantum systems, the cyclic
      evolution of a two-level system is analyzed in terms of the geometric phase
      extended to dissipative systems for Ohmic friction. This proposal is applied to
      the dynamics of chiral molecules where the tunneling and parity violating effects
      are competing. The effect of different system-bath coupling functions in the
      dissipated energy is shown to be crucial to understand the behavior of the
      geometric phase as well as the decoherence displayed by the corresponding
      interference patterns.

PMID- 22583248
TI  - Efficient analysis of highly complex nuclear magnetic resonance spectra of
      flexible solutes in ordered liquids by using molecular dynamics.
AB  - The NMR spectra of n-pentane as solute in the liquid crystal 5CB are measured at
      several temperatures in the nematic phase. Atomistic molecular dynamics
      simulations of this system are carried out to predict the dipolar couplings of
      the orientationally ordered pentane, and the spectra predicted from these
      simulations are compared with the NMR experimental ones. The simulation
      predictions provide an excellent starting point for analysis of the experimental
      NMR spectra using the covariance matrix adaptation evolutionary strategy. This
      shows both the power of atomistic simulations for aiding spectral analysis and
      the success of atomistic molecular dynamics in modeling these anisotropic
      systems.

PMID- 22583249
TI  - Self consistent tight binding model for dissociable water.
AB  - We report results of development of a self consistent tight binding model for
      water. The model explicitly describes the electrons of the liquid self
      consistently, allows dissociation of the water and permits fast direct dynamics
      molecular dynamics calculations of the fluid properties. It is parameterized by
      fitting to first principles calculations on water monomers, dimers, and trimers.
      We report calculated radial distribution functions of the bulk liquid, a phase
      diagram and structure of solvated protons within the model as well as ac
      conductivity of a system of 96 water molecules of which one is dissociated.
      Structural properties and the phase diagram are in good agreement with experiment
      and first principles calculations. The estimated DC conductivity of a
      computational sample containing a dissociated water molecule was an order of
      magnitude larger than that reported from experiment though the calculated ratio
      of proton to hydroxyl contributions to the conductivity is very close to the
      experimental value. The conductivity results suggest a Grotthuss-like mechanism
      for the proton component of the conductivity.

PMID- 22583252
TI  - Transport in nanoporous zeolites: relationships between sorbate size, entropy,
      and diffusivity.
AB  - Molecular dynamics simulations have been performed on monatomic sorbates confined
      within zeolite NaY to obtain the dependence of entropy and self-diffusivity on
      the sorbate diameter. Previously, molecular dynamics simulations by Santikary and
      Yashonath [J. Phys. Chem. 98, 6368 (1994)], theoretical analysis by Derouane et
      al. [J. Catal. 110, 58 (1988)] as well as experiments by Kemball [Adv. Catal. 2,
      233 (1950)] found that certain sorbates in certain adsorbents exhibit unusually
      high self-diffusivity. Experiments showed that the loss of entropy for certain
      sorbates in specific adsorbents was minimum. Kemball suggested that such sorbates
      will have high self-diffusivity in these adsorbents. Entropy of the adsorbed
      phase has been evaluated from the trajectory information by two alternative
      methods: two-phase and multiparticle expansion. The results show that anomalous
      maximum in entropy is also seen as a function of the sorbate diameter. Further,
      the experimental observation of Kemball that minimum loss of entropy is
      associated with maximum in self-diffusivity is found to be true for the system
      studied here. A suitably scaled dimensionless self-diffusivity shows an
      exponential dependence on the excess entropy of the adsorbed phase, analogous to
      excess entropy scaling rules seen in many bulk and confined fluids. The two
      trajectory-based estimators for the entropy show good semiquantitative agreement
      and provide some interesting microscopic insights into entropy changes associated
      with confinement.

PMID- 22583251
TI  - alpha-Scale decoupling of the mechanical relaxation and diverging shear wave
      propagation length scale in triphenylphosphite.
AB  - We have performed depolarized impulsive stimulated scattering experiments to
      observe shear acoustic phonons in supercooled triphenylphosphite (TPP) from ~10
      500 MHz. These measurements, in tandem with previously performed longitudinal and
      shear measurements, permit further analyses of the relaxation dynamics of TPP
      within the framework of the mode coupling theory. Our results provide evidence of
      alpha coupling between the shear and longitudinal degrees of freedom up to a
      decoupling temperature T(c) = 231 K. A lower bound length scale of shear wave
      propagation in liquids verified the exponent predicted by theory in the vicinity
      of the decoupling temperature.

PMID- 22583250
TI  - Determination of the singlet state lifetime of dissolved nitrous oxide from high
      field relaxation measurements.
AB  - Longitudinal spin relaxation due to modulation of dipolar interactions often
      limits the development of hyperpolarized magnetic tracers. Recently, it has been
      demonstrated that transferring spin order to a singlet state significantly
      increases the polarization lifetimes in systems where nitrous oxide is dissolved
      in a liquid solvent. Additionally, previous studies have suggested that the
      longitudinal relaxation of nitrous oxide is largely dominated by the spin
      rotation interaction. Models of spin-relaxation under Brownian motion naively
      predict the angular momentum reorienting correlation time of the spin rotation
      interaction to be inversely proportional to the viscosity of the solution. This
      dependence implies the singlet lifetime can be lengthened by increasing the
      dissolving solvent's viscosity-an extension which is not observed. Our work
      formulates a model which describes the relaxation of nitrous oxide dissolved in
      various solvents. We investigate the effect of altering the temperature of the
      solvent, as well as the effect of varying solute-solvent interactions on the
      singlet state as well as the longitudinal polarization lifetime. We predict the
      singlet lifetime for nitrous oxide dissolved in several solvents by fitting
      rotational and angular momentum correlation times measured at high magnetic
      field, and relate singlet relaxation to translational diffusion constants.

PMID- 22583253
TI  - Controllable transport of water through nanochannel by rachet-like mechanism.
AB  - By using molecular dynamics simulation, we have investigated systematically the
      feasibility of continuous unidirectional water flux across a deformed single
      walled carbon nanotube (SWNT) driven by an oscillating charge outside without
      osmotic pressure or hydrostatic drop. Simulation results indicate that the flux
      is dependent sensitively on the oscillating frequency of the charge, the distance
      of the charge from the SWNT, and the asymmetry of the water-SWNT system. A
      resonance-like phenomenon is found that the water flux is enhanced significantly
      when the period of the oscillation is close to twice the average hopping time of
      water molecules inside the SWNT. These findings are helpful in developing a novel
      design of efficient functional nanofluidic devices.

PMID- 22583254
TI  - Crystal structure of ammonia dihydrate II.
AB  - We have used density-functional-theory (DFT) methods together with a structure
      searching algorithm to make an experimentally constrained prediction of the
      structure of ammonia dihydrate II (ADH-II). The DFT structure is in good
      agreement with neutron diffraction data and verifies the prediction. The
      structure consists of the same basic structural elements as ADH-I, with a modest
      alteration to the packing, but a considerable reduction in volume. The phase
      diagram of the known ADH and ammonia monohydrate + water-ice structures is
      calculated with the Perdew-Burke-Ernzerhof density functional, and the effects of
      a semi-empirical dispersion corrected functional are investigated. The results of
      our DFT calculations of the finite-pressure elastic constants of ADH-II are
      compared with the available experimental data for the elastic strain
      coefficients.

PMID- 22583255
TI  - Bifurcation transitions in a photochemical system under low magnetic fields.
AB  - In the last decades, the effect of low magnetic fields on biochemical and
      chemical systems has been an urgent problem. By now numerous experimental and
      theoretical studies have been conducted to demonstrate that commonly this effect
      is of no essence as it does not exceed 10%. However, there are experimental works
      which testify that in some systems, magnetic field effects are more significant.
      Thus, of great interest is an active search for rather simple but realistic
      models that are based on physically explicit assumptions and able to account for
      a strong effect of low magnetic fields. The present work not only offers a
      theoretical study on the simplest photochemical system, describing a reversible
      reaction of photodissociation, but also shows how a low magnetic field can
      strongly modify its properties under highly nonequilibrium conditions. It is
      assumed that external magnetic field can have effect on the rates of radical
      reactions occurring in a system. This, in turn, leads to bifurcation of the
      nonequilibrium stationary state and, thus, to a drastic change in the properties
      of chemical systems (temperature and reagent concentration).

PMID- 22583256
TI  - Study of the pair correlations between p-nitroaniline molecules in solution by
      depolarized hyper-Rayleigh scattering.
AB  - The concentration dependence of the hyper-Rayleigh scattering depolarization
      ratios of p-nitroaniline in solution was obtained and the results were compared
      with theory. It was found that the experimental data can be theoretically
      accounted for by using a pair distribution function that includes only direct
      correlation, with the molecules interact through a dipolar hard-sphere potential.
      The results show that short-range dipole-dipole interactions are responsible for
      the correlation between pairs of p-nitroaniline molecules in solution.

PMID- 22583257
TI  - Enthalpy recovery in glassy materials: heterogeneous versus homogenous models.
AB  - Models of enthalpy relaxations of glasses are the basis for understanding
      physical aging, scanning calorimetry, and other phenomena that involve non
      equilibrium and non-linear dynamics. We compare models in terms of the nature of
      the relaxation dynamics, heterogeneous versus homogeneous, with focus on the
      Kovacs-Aklonis-Hutchinson-Ramos (KAHR) and the Tool-Narayanaswamy-Moynihan (TNM)
      approaches. Of particular interest is identifying the situations for which
      experimental data are capable of discriminating the heterogeneous from the
      homogeneous scenario. The ad hoc assumption of a single fictive temperature,
      T(f), is common to many models, including KAHR and TNM. It is shown that only for
      such single-T(f) models, enthalpy relaxation of a glass is a two-point
      correlation function in reduced time, implying that experimental results are not
      decisive regarding the underlying nature of the dynamics of enthalpy relaxation.
      We also find that the restriction of the common TNM model to a Kohlrausch
      Williams-Watts type relaxation pattern limits the applicability of this approach,
      as the particular choice regarding the distribution of relaxation times is a more
      critical factor compared with isothermal relaxation experiments. As a result,
      significant improvements in fitting calorimetry data can be achieved with subtle
      adjustments in the underlying relaxation time distribution.

PMID- 22583258
TI  - Fluctuations and micro-heterogeneity in aqueous mixtures.
AB  - The problem as to why water-water density correlations are systematically
      overestimated in computer simulation of aqueous mixtures is examined through an
      extensive molecular dynamics study of mixtures of the extended single point
      charge water model with a fully miscible weaker version of it, obtained by
      scaling down the site partial charges by a factor 2/3, thereby eliminating solute
      solvent size differences. The study reveals that enhanced water correlations is a
      genuine physical effect, and are not an artifact of the simulations or the
      models, as previously suggested in the context of realistic aqueous mixtures.
      Rather, they correspond to the existence of strongly correlated water domains,
      for "weak-water" mole fraction x > 0.4, that modulate the spatial decay of the
      density correlations. These domains produce a prepeak in the structure factor,
      suggesting that simple aqueous mixture might behave just like micro-emulsions.
      The overestimated long range water correlations result from incorrect predictions
      of the asymptote of these correlations, which themselves arise from size
      limitations of the simulation box. However, by requiring consistency between
      thermodynamical and structural expressions of the concentration fluctuations, a
      method to predict the proper decay of the correlation function is obtained
      herein, inspired by the formal analogy with micro-emulsions. This study provides
      a new insight for the large values of the experimental Kirkwood-Buff integrals
      for many aqueous mixtures: these mixtures are in a Lifshitz-type regime, where
      concentration fluctuations compete with water domain formation.

PMID- 22583259
TI  - Local structure of titania decorated double-walled carbon nanotube characterized
      by scanning transmission X-ray microscopy.
AB  - Scanning transmission X-ray microscopy was demonstrated to deliver detailed local
      structure and chemical composition of a complicated system with titania
      nanoparticles dispersed inside and outside the double-walled carbon nanotube
      (DWNT) channels. Areas with inhomogeneous distribution of titania and the
      associated water were particularly investigated at the C K-edge, Ti L-edge, and O
      K-edge. The results show that titania nanoparticles located inside DWNTs are
      present as amorphous, while those unsuccessfully introduced into the channels
      behave more like bulk materials in forms of anatase and rutile. Strong
      interaction was detected between the confined titania and DWNTs, as evidenced by
      up to 0.6 eV energy shift at the Ti L-edge. Strong hydration was observed for the
      as-prepared samples. Functionalization due to reduction and oxidation between
      titania and carbon layer is observed upon heat-treatment. This detailed
      structural information of specific areas cannot be provided by other techniques
      such as HRTEM, XRD, and XANES.

PMID- 22583260
TI  - Motion of a colloidal sphere with interfacial self-electrochemical reactions
      induced by a magnetic field.
AB  - The motion of a spherical colloidal particle with spontaneous electrochemical
      reactions occurring on its surface in an ionic solution subjected to an applied
      magnetic field is analyzed for an arbitrary zeta potential distribution. The
      thickness of the electric double layer adjacent to the particle surface is
      assumed to be much less than the particle radius. The solutions of the Laplace
      equations governing the magnetic scalar potential and electric potential,
      respectively, lead to the magnetic flux and electric current density
      distributions in the particle and fluid phases of arbitrary magnetic
      permeabilities and electric conductivities. The Stokes equations modified with
      the Lorentz force contribution for the fluid motion are dealt by using a
      generalized reciprocal theorem, and closed-form formulas for the translational
      and angular velocities of the colloidal sphere induced by the magnetohydrodynamic
      effect are obtained. The dipole and quadrupole moments of the zeta potential
      distribution over the particle surface cause the particle translation and
      rotation, respectively. The induced velocities of the particle are unexpectedly
      significant, and their dependence on the characteristics of the particle-fluid
      system is physically different from that for electromagnetophoretic particles or
      phoretic swimmers.

PMID- 22583261
TI  - Application of double-hybrid density functionals to charge transfer in N
      substituted pentacenequinones.
AB  - A set of N-heteroquinones, deriving from oligoacenes, have been recently proposed
      as n-type organic semiconductors with high electron mobilities in thin-film
      transistors. Generally speaking, this class of compounds self-assembles in
      neighboring pi-stacks linked by weak hydrogen bonds. We aim at theoretically
      characterizing here the sequential charge transport (hopping) process expected to
      take place across these arrays of molecules. To do so, we need to accurately
      address the preferred packing of these materials simultaneously to single
      molecule properties related to charge-transfer events, carefully employing
      dispersion-corrected density functional theory methods to accurately extract the
      key molecular parameters governing this phenomenon at the nanoscale. This study
      confirms the great deal of interest around these compounds, since controlled
      functionalization of model molecules (i.e., pentacene) allows to efficiently tune
      the corresponding charge mobilities, and the capacity of modern quantum-chemical
      methods to predict it after rationalizing the underlying structure-property
      relationships.

PMID- 22583262
TI  - Nanowelding of carbon nanotube-metal contacts: an effective way to control the
      Schottky barrier and performance of carbon nanotube based field effect
      transistors.
AB  - Schottky barriers formed at carbon nanotube (CNT)-metal contacts have been well
      known to be crucial for the performance of CNT based field effect transistors
      (FETs). Through first principles calculations we show that a nanowelding process
      can drastically reduce the Schottky barriers at CNT-metal interfaces, resulting
      in significantly improved conductivity of CNT-based FETs. The proposed
      nanowelding can be realized by either laser local heating or a heating process
      via a controllable pulse current. Results presented in this paper may have great
      implications in future design and applications of CNT-based electronics.

PMID- 22583263
TI  - Phase ordering of hard needles on a quasicrystalline substrate.
AB  - Quasicrystals possess long-range positional and orientational order. However,
      they cannot be periodic in space due to their non-crystallographic symmetries
      such as a 10-fold rotational axis. We perform Monte Carlo simulations of two
      dimensional hard-needle systems subject to a quasiperiodic substrate potential.
      We determine phase diagrams as a function of density and potential strength for
      two needle lengths. With increasing potential strength short needles tend to form
      isolated clusters that display directional order along the decagonal directions.
      Long needles create interacting clusters that stabilize the nematic phase. At
      large potential strengths the clusters position themselves on two interwoven
      Fibonacci sequences perpendicular to the cluster orientation. Alternatively, one
      obtains extended domains of needle clusters which are aligned along all decagonal
      symmetry directions.

PMID- 22583264
TI  - Adsorption, mobility, and dimerization of benzaldehyde on Pt(111).
AB  - Building on results for the adsorption of benzene on Pt(111), the adsorption of
      benzaldehyde is investigated using density functional theory. Benzaldehyde is
      found to chemisorb preferentially with its aromatic ring in the flat-lying bridge
      geometry that is also preferred for benzene. Across the investigated geometries,
      adsorption is homogeneously weakened compared to corresponding benzene
      geometries. This is found to be true for very different adsorption modes, namely,
      eta(6) and eta(8) modes, the latter having metal atoms inserted in the carbonyl
      bond. Reorientation and diffusion of benzaldehyde is found to have low energy
      barriers. Aggregation of molecules in dimers bound by aryl C-H...O hydrogen bonds
      is investigated, and specific configurations are found to be up to 0.15 eV more
      favorable than optimally configured, separated adsorbates. The binding is
      significantly stronger than what is found for gas phase dimers, suggesting an
      enhancing effect of the metal interaction.

PMID- 22583265
TI  - Self-assembly of model amphiphilic Janus particles.
AB  - We apply molecular dynamics simulations to investigate the structure formation of
      amphiphilic Janus particles in the bulk phase. The Janus particles are modeled as
      (soft) spheres composed of a hydrophilic and hydrophobic part. Their orientation
      is described by a vector representing an internal degree of freedom.
      Investigating energy fluctuations and cluster size distributions, we determine
      the aggregation line in a temperature-density-diagram, where the reduced
      temperature is an inverse measure for the anisotropic coupling. Below this
      aggregation line clusters of various sizes depending on density and reduced
      temperature are found. For low densities in the range rho* <= 0.3, the cluster
      size distribution has a broad maximum, indicating simultaneous existence of
      various cluster sizes between 5 and 10. We find no hint of a condensation
      transition of these clustered systems. In the case of higher densities (rho* =
      0.5 and 0.6), the cluster size distribution shows an extremely narrow peak at
      clusters of size 13. In these icosahedrons, the particles are arranged in a
      closed-packed manner, thereby maximizing the number of bonds. Analyzing the
      translational mean-square displacement we also observe indications of hindered
      diffusion due to aggregation.

PMID- 22583266
TI  - How does water-nanotube interaction influence water flow through the nanochannel?
AB  - Water permeation across various nitrogen-doped double-walled carbon nanotubes (N
      DWCNT) has been studied with molecular dynamics simulations to better understand
      the influence of water-nanopore interaction on the water permeation rate. There
      exists a threshold interaction energy at around -34.1 kJ/mol. Over the threshold
      energy, the water flow through N-DWCNT decreases monotonically with the
      strengthening of the water-nanotube interaction. The effect on the water flow
      across the channel is found to be negligible when the interaction energy is
      weaker than the threshold. The water-nanotube interaction energy can be
      controlled by doping nitrogen atoms into the nanotube walls. Although the van der
      Waals interaction energy is much stronger than the electrostatic interaction
      energy, it is less sensitive to the proportion of doped nitrogen atoms. On the
      other hand, the electrostatic interaction energy weakens after the initial
      strengthening when the percentage of doped nitrogen atoms increases to ~25%. The
      doped nitrogen atoms make less influence on the overall electrostatic interaction
      energy when the proportion is over 25%, due to the repulsions among themselves.
      Thus, the monotonous strengthening of the van der Waals interaction energy seems
      to dominate the overall trend of the total interaction energy, whereas the change
      of the long-range electrostatic interaction energy characterizes the shape of the
      correlation curve, as the percentage of doped nitrogen atoms increases.

PMID- 22583268
TI  - First passage times for a tracer particle in single file diffusion and fractional
      Brownian motion.
AB  - We investigate the full functional form of the first passage time density (FPTD)
      of a tracer particle in a single-file diffusion (SFD) system whose population is:
      (i) homogeneous, i.e., all particles having the same diffusion constant and (ii)
      heterogeneous, with diffusion constants drawn from a heavy-tailed power-law
      distribution. In parallel, the full FPTD for fractional Brownian motion [fBm
      defined by the Hurst parameter, H ? (0, 1)] is studied, of interest here as fBm
      and SFD systems belong to the same universality class. Extensive stochastic (non
      Markovian) SFD and fBm simulations are performed and compared to two analytical
      Markovian techniques: the method of images approximation (MIA) and the Willemski
      Fixman approximation (WFA). We find that the MIA cannot approximate well any
      temporal scale of the SFD FPTD. Our exact inversion of the Willemski-Fixman
      integral equation captures the long-time power-law exponent, when H >= 1/3, as
      predicted by Molchan [Commun. Math. Phys. 205, 97 (1999)] for fBm. When H < 1/3,
      which includes homogeneous SFD (H = 1/4), and heterogeneous SFD (H < 1/4), the
      WFA fails to agree with any temporal scale of the simulations and Molchan's long
      time result. SFD systems are compared to their fBm counter parts; and in the
      homogeneous system both scaled FPTDs agree on all temporal scales including also,
      the result by Molchan, thus affirming that SFD and fBm dynamics belong to the
      same universality class. In the heterogeneous case SFD and fBm results for
      heterogeneity-averaged FPTDs agree in the asymptotic time limit. The non-averaged
      heterogeneous SFD systems display a lack of self-averaging. An exponential with a
      power-law argument, multiplied by a power-law pre-factor is shown to describe
      well the FPTD for all times for homogeneous SFD and sub-diffusive fBm systems.

PMID- 22583267
TI  - Osmotic virial coefficients for model protein and colloidal solutions: importance
      of ensemble constraints in the analysis of light scattering data.
AB  - Protein-protein interactions in solution may be quantified by the osmotic second
      virial coefficient (OSVC), which can be measured by various experimental
      techniques including light scattering. Analysis of Rayleigh light scattering
      measurements from such experiments requires identification of a scattering volume
      and the thermodynamic constraints imposed on that volume, i.e., the statistical
      mechanical ensemble in which light scattering occurs. Depending on the set of
      constraints imposed on the scattering volume, one can obtain either an apparent
      OSVC, A(2,app), or the true thermodynamic OSVC, B(22)(osm), that is rigorously
      defined in solution theory [M. A. Blanco, E. Sahin, Y. Li, and C. J. Roberts, J.
      Chem. Phys. 134, 225103 (2011)]. However, it is unclear to what extent A(2,app)
      and B(22)(osm) differ, which may have implications on the physical interpretation
      of OSVC measurements from light scattering experiments. In this paper, we use the
      multicomponent hard-sphere model and a well-known equation of state to directly
      compare A(2,app) and B(22)(osm). Our results from the hard-sphere equation of
      state indicate that A(2,app) underestimates B(22)(osm), but in a systematic
      manner that may be explained using fundamental thermodynamic expressions for the
      two OSVCs. The difference between A(2,app) and B(22)(osm) may be quantitatively
      significant, but may also be obscured in experimental application by statistical
      uncertainty or non-steric interactions. Consequently, the two OSVCs that arise in
      the analysis of light scattering measurements do formally differ, but in a manner
      that may not be detectable in actual application.

PMID- 22583270
TI  - Communication: electronic band gaps of semiconducting zig-zag carbon nanotubes
      from many-body perturbation theory calculations.
AB  - Electronic band gaps for optically allowed transitions are calculated for a
      series of semiconducting single-walled zig-zag carbon nanotubes of increasing
      diameter within the many-body perturbation theory GW method. The dependence of
      the evaluated gaps with respect to tube diameters is then compared with those
      found from previous experimental data for optical gaps combined with theoretical
      estimations of exciton binding energies. We find that our GW gaps confirm the
      behavior inferred from experiment. The relationship between the electronic gap
      and the diameter extrapolated from the GW values is also in excellent agreement
      with a direct measurement recently performed through scanning tunneling
      spectroscopy.

PMID- 22583269
TI  - Multipartite entanglement in the Fenna-Matthews-Olson (FMO) pigment-protein
      complex.
AB  - We investigate multipartite states in the Fenna-Matthews-Olson (FMO) pigment
      protein complex of the green sulfur bacteria using a Lorentzian spectral density
      of the phonon reservoir fitted with typical parameter estimates of the species,
      Prosthecochloris aestuarii. The evolution of the entanglement measure of the
      excitonic W qubit states is evaluated in the picosecond time range, showing
      increased revivals in the non-Markovian regime. Similar trends are observed in
      the evolution dynamics of the Meyer-Wallach measure of the N-exciton multipartite
      state, with results showing that multipartite entanglement can last from 0.5 to 1
      ps, between the bacteriochlorophylls of the FMO complex. The teleportation and
      quantum information splitting fidelities associated with the Greenberger-Horne
      Zeilinger and W-like resource states formed by the excitonic qubit channels of
      the FMO complex show that revivals in fidelities increase with the degree of non
      Markovian strength of the decoherent environment. Quantum information processing
      tasks involving teleportation followed by the decodification process involving W
      like states of the FMO complex may play a critical role during coherent
      oscillations at physiological temperatures.

PMID- 22583271
TI  - An adaptive stepsize method for the chemical Langevin equation.
AB  - Mathematical and computational modeling are key tools in analyzing important
      biological processes in cells and living organisms. In particular, stochastic
      models are essential to accurately describe the cellular dynamics, when the
      assumption of the thermodynamic limit can no longer be applied. However,
      stochastic models are computationally much more challenging than the traditional
      deterministic models. Moreover, many biochemical systems arising in applications
      have multiple time-scales, which lead to mathematical stiffness. In this paper we
      investigate the numerical solution of a stochastic continuous model of well
      stirred biochemical systems, the chemical Langevin equation. The chemical
      Langevin equation is a stochastic differential equation with multiplicative, non
      commutative noise. We propose an adaptive stepsize algorithm for approximating
      the solution of models of biochemical systems in the Langevin regime, with small
      noise, based on estimates of the local error. The underlying numerical method is
      the Milstein scheme. The proposed adaptive method is tested on several examples
      arising in applications and it is shown to have improved efficiency and accuracy
      compared to the existing fixed stepsize schemes.

PMID- 22583272
TI  - Hyper-generalized-gradient functionals constructed from the Lieb-Oxford bound:
      implementation via local hybrids and thermochemical assessment.
AB  - In 2009 Odashima and Capelle (OC) showed a way to design a correlation-only
      density functional that satisfies a Lieb-Oxford bound on the correlation energy,
      without empirical parameters and even without additional theoretical parameters.
      However, they were only able to test a size-inconsistent version of it that
      employs total energies. Here, we show that their alternative size-consistent form
      that employs energy densities, when combined with exact or semilocal exchange, is
      a local hybrid (lh) functional. We test several variants of this nonempirical OC
      lh functional on standard molecular test sets. Although no variant yields
      enthalpies of formation with the accuracy of the semilocal Tao-Perdew-Staroverov
      Scuseria (TPSS) exchange-correlation, OC-lh correlation with exact exchange
      yields rather accurate energy barriers for chemical reactions. Our purpose here
      is not to advocate for a new density functional, but to explore a previously
      published idea. We also discuss the importance of near-self-consistency for fully
      nonlocal functionals.

PMID- 22583273
TI  - A quantum generalization of intrinsic reaction coordinate using path integral
      centroid coordinates.
AB  - We propose a generalization of the intrinsic reaction coordinate (IRC) for
      quantum many-body systems described in terms of the mass-weighted ring polymer
      centroids in the imaginary-time path integral theory. This novel kind of reaction
      coordinate, which may be called the "centroid IRC," corresponds to the minimum
      free energy path connecting reactant and product states with a least amount of
      reversible work applied to the center of masses of the quantum nuclei, i.e., the
      centroids. We provide a numerical procedure to obtain the centroid IRC based on
      first principles by combining ab initio path integral simulation with the string
      method. This approach is applied to NH(3) molecule and N(2)H(5) (-) ion as well
      as their deuterated isotopomers to study the importance of nuclear quantum
      effects in the intramolecular and intermolecular proton transfer reactions. We
      find that, in the intramolecular proton transfer (inversion) of NH(3), the free
      energy barrier for the centroid variables decreases with an amount of about 20%
      compared to the classical one at the room temperature. In the intermolecular
      proton transfer of N(2)H(5) (-), the centroid IRC is largely deviated from the
      "classical" IRC, and the free energy barrier is reduced by the quantum effects
      even more drastically.

PMID- 22583274
TI  - A temperature behavior of the frustrated translational mode of adsorbate and the
      nature of the "adsorbate-substrate" interaction.
AB  - A temperature behavior of the frustrated translational mode (T-mode) of a light
      particle, coupled by different regimes of ohmicity to the surface, is studied
      within a formalism of the generalized diffusion coefficients. The memory effects
      of the adsorbate motion are considered to be the main reason of the T-mode
      origin. Numerical calculations yield a thermally induced shift and broadening of
      the T-mode, which is found to be linear in temperature for Ohmic and super-Ohmic
      systems and nonlinear for strongly sub-Ohmic ones. We obtain analytical
      expressions for the T-mode shift and width at weak coupling for the systems with
      integer "ohmicity" indexes n = 0/2 in zero temperature and high temperature
      limits. We provide an explanation of the experimentally observed blue- or
      redshifts of the T-mode on the basis of a comparative analysis of two typical
      times of the system evolution: a time of decay of the "velocity-velocity"
      autocorrelation function, and a correlation time of the thermal bath random
      forces. A relation of the T-mode to the multiple jumps of the adsorbate is
      discussed, and generalization of conditions of the multiple hopping to the case
      of quantum surface diffusion is performed.

PMID- 22583275
TI  - Excitation energies from range-separated time-dependent density and density
      matrix functional theory.
AB  - Time-dependent density functional theory (TD-DFT) in the adiabatic formulation
      exhibits known failures when applied to predicting excitation energies. One of
      them is the lack of the doubly excited configurations. On the other hand, the
      time-dependent theory based on a one-electron reduced density matrix functional
      (time-dependent density matrix functional theory, TD-DMFT) has proven accurate in
      determining single and double excitations of H(2) molecule if the exact
      functional is employed in the adiabatic approximation. We propose a new approach
      for computing excited state energies that relies on functionals of electron
      density and one-electron reduced density matrix, where the latter is applied in
      the long-range region of electron-electron interactions. A similar approach has
      been recently successfully employed in predicting ground state potential energy
      curves of diatomic molecules even in the dissociation limit, where static
      correlation effects are dominating. In the paper, a time-dependent functional
      theory based on the range-separation of electronic interaction operator is
      rigorously formulated. To turn the approach into a practical scheme the adiabatic
      approximation is proposed for the short- and long-range components of the
      coupling matrix present in the linear response equations. In the end, the problem
      of finding excitation energies is turned into an eigenproblem for a symmetric
      matrix. Assignment of obtained excitations is discussed and it is shown how to
      identify double excitations from the analysis of approximate transition density
      matrix elements. The proposed method used with the short-range local density
      approximation (srLDA) and the long-range Buijse-Baerends density matrix
      functional (lrBB) is applied to H(2) molecule (at equilibrium geometry and in the
      dissociation limit) and to Be atom. The method accounts for double excitations in
      the investigated systems but, unfortunately, the accuracy of some of them is
      poor. The quality of the other excitations is in general much better than that
      offered by TD-DFT-LDA or TD-DMFT-BB approximations if the range-separation
      parameter is properly chosen. The latter remains an open problem.

PMID- 22583276
TI  - Equivalence between the mechanical model and energy-transfer theory for the
      classical decay rates of molecules near a spherical particle.
AB  - In the classical modeling of decay rates for molecules interacting with a
      nontrivial environment, it is well known that two alternate approaches exist
      which include: (1) a mechanical model treating the system as a damped harmonic
      oscillator driven by the reflected fields from the environment; and (2) a model
      based on the radiative and nonradiative energy transfers from the excited
      molecular system to the environment. While the exact equivalence of the two
      methods is not trivial and has been explicitly demonstrated only for planar
      geometry, it has been widely taken for granted and applied to other geometries
      such as in the interaction of the molecule with a spherical particle. Here we
      provide a rigorous proof of such equivalence for the molecule-sphere problem via
      a direct calculation of the decay rates adopting each of the two different
      approaches.

PMID- 22583277
TI  - Evaluation of the grand-canonical partition function using expanded Wang-Landau
      simulations. I. Thermodynamic properties in the bulk and at the liquid-vapor
      phase boundary.
AB  - The Wang-Landau sampling is a powerful method that allows for a direct
      determination of the density of states. However, applications to the calculation
      of the thermodynamic properties of realistic fluids have been limited so far. By
      combining the Wang-Landau method with expanded grand-canonical simulations, we
      obtain a high-accuracy estimate for the grand-canonical partition function for
      atomic and molecular fluids. Then, using the formalism of statistical
      thermodynamics, we are able to calculate the thermodynamic properties of these
      systems, for a wide range of conditions spanning the single-phase regions as well
      as the vapor-liquid phase boundary. Excellent agreement with prior simulation
      work and with the available experimental data is obtained for argon and CO(2),
      thereby establishing the accuracy of the method for the calculation of
      thermodynamic properties such as free energies and entropies.

PMID- 22583278
TI  - Evaluation of the grand-canonical partition function using expanded Wang-Landau
      simulations. II. Adsorption of atomic and molecular fluids in a porous material.
AB  - We propose to apply expanded Wang-Landau simulations to study the adsorption of
      atomic and molecular fluids in porous materials. This approach relies on a
      uniform sampling of the number of atoms and molecules adsorbed. The method
      consists in determining a high-accuracy estimate of the grand-canonical partition
      function for the adsorbed fluids. Then, using the formalism of statistical
      mechanics, we calculate absolute and excess thermodynamic properties relevant to
      adsorption processes. In this paper, we examine the adsorption of argon and
      carbon dioxide in the isoreticular metal-organic framework (IRMOF-1). We assess
      the reliability of the method by showing that the predicted adsorption isotherms
      and isosteric heats are in excellent agreement with simulation results obtained
      from grand-canonical Monte Carlo simulations. We also show that the proposed
      method is very efficient since a single expanded Wang-Landau simulation run at a
      given temperature provides the whole adsorption isotherm. Moreover, this approach
      provides a direct access to a wide range of thermodynamic properties, such as,
      e.g., the excess Gibbs free energy and the excess entropy of adsorption.

PMID- 22583279
TI  - A master-equation approach to simulate kinetic traps during directed self
      assembly.
AB  - Robust directed self-assembly of non-periodic nanoscale structures is a key
      process that would enable various technological breakthroughs. The dynamic
      evolution of directed self-assemblies towards structures with desired geometries
      is governed by the rugged potential energy surface of nanoscale systems,
      potentially leading the system to kinetic traps. To study such phenomena and to
      set the framework for the directed self-assembly of nanoparticles towards
      structures with desired geometries, the development of a dynamic model involving
      a master equation to simulate the directed self-assembly process is presented.
      The model describes the probability of each possible configuration of a fixed
      number of nanoparticles on a domain, including parametric sensitivities that can
      be used for optimization, as a function of time during self-assembly. An
      algorithm is presented that solves large-scale instances of the model with linear
      computational complexity. Case studies illustrate the influence of several
      degrees of freedom on directed self-assembly. A design approach that
      systematically decomposes the ergodicity of the system to direct self-assembly of
      a targeted configuration with high probability is illustrated. The prospects for
      extending such an approach to larger systems using coarse graining techniques are
      also discussed.

PMID- 22583280
TI  - Comparisons of classical chemical dynamics simulations of the unimolecular
      decomposition of classical and quantum microcanonical ensembles.
AB  - Previous studies have shown that classical trajectory simulations often give
      accurate results for short-time intramolecular and unimolecular dynamics,
      particularly for initial non-random energy distributions. To obtain such
      agreement between experiment and simulation, the appropriate distributions must
      be sampled to choose initial coordinates and momenta for the ensemble of
      trajectories. If a molecule's classical phase space is sampled randomly, its
      initial decomposition will give the classical anharmonic microcanonical (RRKM)
      unimolecular rate constant for its decomposition. For the work presented here,
      classical trajectory simulations of the unimolecular decomposition of quantum and
      classical microcanonical ensembles, at the same fixed total energy, are compared.
      In contrast to the classical microcanonical ensemble, the quantum microcanonical
      ensemble does not sample the phase space randomly. The simulations were performed
      for CH(4), C(2)H(5), and Cl(-)---CH(3)Br using both analytic potential energy
      surfaces and direct dynamics methods. Previous studies identified intrinsic RRKM
      dynamics for CH(4) and C(2)H(5), but intrinsic non-RRKM dynamics for Cl(-)--
      CH(3)Br. Rate constants calculated from trajectories obtained by the time
      propagation of the classical and quantum microcanonical ensembles are compared
      with the corresponding harmonic RRKM estimates to obtain anharmonic corrections
      to the RRKM rate constants. The relevance and accuracy of the classical
      trajectory simulation of the quantum microcanonical ensemble, for obtaining the
      quantum anharmonic RRKM rate constant, is discussed.

PMID- 22583281
TI  - Electron attachment to molecules in a cluster environment.
AB  - Low-energy dissociative electron attachment (DEA) to the CF(2)Cl(2) and CF(3)Cl
      molecules in a water cluster environment is investigated theoretically.
      Calculations are performed for the water trimer and water hexamer. It is shown
      that the DEA cross section is strongly enhanced when the attaching molecule is
      embedded in a water cluster, and that this cross section grows as the number of
      water molecules in the cluster increases. This growth is explained by a trapping
      effect that is due to multiple scattering by water molecules while the electron
      is trapped in the cluster environment. The trapping increases the resonance
      lifetime and the negative ion survival probability. This confirms qualitatively
      existing experiments on electron attachment to the CF(2)Cl(2) molecule placed on
      the surface of H(2)O ice. The DEA cross sections are shown to be very sensitive
      to the position of the attaching molecule within the cluster and the orientation
      of the electron beam relative to the cluster.

PMID- 22583282
TI  - Quantum and classical approaches for rotational relaxation and nonresonant laser
      alignment of linear molecules: a comparison for CO2 gas in the nonadiabatic
      regime.
AB  - A quantum approach and classical molecular dynamics simulations (CMDS) are
      proposed for the modeling of rotational relaxation and of the nonadiabatic
      alignment of gaseous linear molecules by a nonresonant laser field under
      dissipative conditions. They are applied to pure CO(2) and compared by looking at
      state-to-state collisional rates and at the value of <cos(2)[theta(z)(t)]>
      induced by a 100 fs laser pulse linearly polarized along z[overhead arrow]. The
      main results are: (i) When properly requantized, the classical model leads to
      very satisfactory predictions of the permanent and transient alignments under non
      dissipative conditions. (ii) The CMDS calculations of collisional-broadening
      coefficients and rotational state-to-state rates are in very good agreement with
      those of a quantum model based on the energy corrected sudden (ECS)
      approximation. (iii) Both approaches show a strong propensity of collisions,
      while they change the rotational energy (i.e., J), to conserve the angular
      momentum orientation (i.e., M/J). (iv) Under dissipative conditions, CMDS and
      quantum-ECS calculations lead to very consistent decays with time of the
      "permanent" and transient components of the laser-induced alignment. This result,
      expected from (i) and (ii), is obtained only if a properly J- and M-dependent ECS
      model is used. Indeed, rotational state-to-state rates and the decay of the
      "permanent" alignment demonstrate, for pure CO(2), the limits of a M-independent
      collisional model proposed previously. Furthermore, computations show that
      collisions induce a decay of the "permanent" alignment about twice slower than
      that of the transient revivals amplitudes, a direct consequence of (iii). (v) The
      analysis of the effects of reorienting and dephasing elastic collisions shows
      that the latter have a very small influence but that the former play a non
      negligible role in the alignment dynamics. (vi) Rotation-translation
      collisionally induced transfers have also been studied, demonstrating that they
      only slightly change the alignment dissipation for the considered laser energy
      conditions.

PMID- 22583283
TI  - Calibration-quality adiabatic potential energy surfaces for H3(+) and its
      isotopologues.
AB  - Calibration-quality ab initio adiabatic potential energy surfaces (PES) have been
      determined for all isotopologues of the molecular ion H(3)(+). The underlying
      Born-Oppenheimer electronic structure computations used optimized explicitly
      correlated shifted Gaussian functions. The surfaces include diagonal Born
      Oppenheimer corrections computed from the accurate electronic wave functions. A
      fit to the 41,655 ab initio points is presented which gives a standard deviation
      better than 0.1 cm(-1) when restricted to the points up to 6000 cm(-1) above the
      first dissociation asymptote. Nuclear motion calculations utilizing this PES,
      called GLH3P, and an exact kinetic energy operator given in orthogonal internal
      coordinates are presented. The ro-vibrational transition frequencies for H(3)(+),
      H(2)D(+), and HD(2)(+) are compared with high resolution measurements. The most
      sophisticated and complete procedure employed to compute ro-vibrational energy
      levels, which makes explicit allowance for the inclusion of non-adiabatic
      effects, reproduces all the known ro-vibrational levels of the H(3)(+)
      isotopologues considered to better than 0.2 cm(-1). This represents a significant
      (order-of-magnitude) improvement compared to previous studies of transitions in
      the visible. Careful treatment of linear geometries is important for high
      frequency transitions and leads to new assignments for some of the previously
      observed lines. Prospects for further investigations of non-adiabatic effects in
      the H(3)(+) isotopologues are discussed. In short, the paper presents (a) an
      extremely accurate global potential energy surface of H(3)(+) resulting from high
      accuracy ab initio computations and global fit, (b) very accurate nuclear motion
      calculations of all available experimental line data up to 16,000 cm(-1), and (c)
      results suggest that we can predict accurately the lines of H(3)(+) towards
      dissociation and thus facilitate their experimental observation.

PMID- 22583284
TI  - Efficient quantum-classical method for computing thermal rate constant of
      recombination: application to ozone formation.
AB  - Efficient method is proposed for computing thermal rate constant of recombination
      reaction that proceeds according to the energy transfer mechanism, when an
      energized molecule is formed from reactants first, and is stabilized later by
      collision with quencher. The mixed quantum-classical theory for the collisional
      energy transfer and the ro-vibrational energy flow [M. Ivanov and D. Babikov, J.
      Chem. Phys. 134, 144107 (2011)] is employed to treat the dynamics of molecule +
      quencher collision. Efficiency is achieved by sampling simultaneously (i) the
      thermal collision energy, (ii) the impact parameter, and (iii) the incident
      direction of quencher, as well as (iv) the rotational state of energized
      molecule. This approach is applied to calculate third-order rate constant of the
      recombination reaction that forms the (16)O(18)O(16)O isotopomer of ozone.
      Comparison of the predicted rate vs. experimental result is presented.

PMID- 22583285
TI  - Identification of the dimethylamine-trimethylamine complex in the gas phase.
AB  - We have identified the dimethylamine-trimethylamine complex (DMA-TMA) at room
      temperature in the gas phase. The Fourier transform infrared (FTIR) spectrum of
      DMA-TMA in the NH-stretching fundamental region was obtained by spectral
      subtraction of spectra of each monomer. Explicitly correlated coupled cluster
      calculations were used to determine the minimum energy structure and interaction
      energy of DMA-TMA. Frequencies and intensities of NH-stretching transitions were
      also calculated at this level of theory with an anharmonic oscillator local mode
      model. The fundamental NH-stretching intensity in DMA-TMA is calculated to be
      approximately 700 times larger than that of the DMA monomer. The measured and
      calculated intensity is used to determine a room temperature equilibrium constant
      of DMA-TMA of 1.7 * 10(-3) atm(-1) at 298 K.

PMID- 22583286
TI  - Experimental and computational investigation of the group 11-group 2 diatomic
      molecules: first determination of the AuSr and AuBa bond energies and
      thermodynamic stability of the copper- and silver-alkaline earth species.
AB  - The dissociation energies of the intermetallic molecules AuSr and AuBa were for
      the first time determined by the Knudsen effusion mass spectrometry method. The
      two species were produced in the vapor phase equilibrated with apt mixtures of
      the constituent elements, and the dissociation equilibria were monitored mass
      spectrometrically in the temperature range 1406-1971 K (AuSr) and 1505-1971 K
      (AuBa). The third-law analysis of the equilibrium data gives the following
      dissociation energies (D(0) degrees , in kJ/mol): 244.4 +/- 4.8 (AuSr) and 273.3
      +/- 6.3 (AuBa), so completing the series of D(0) degrees s for the AuAE (AE =
      group 2 element) diatomics. The AuAE species were also studied computationally at
      the coupled cluster including single, double and perturbative triple excitation
      [CCSD(T)] level with basis sets of increasing zeta quality, and various complete
      basis set limit extrapolations were performed to calculate the dissociation
      energies. Furthermore, the entire series of the heteronuclear diatomic species
      formed from one group 11 (Cu, Ag) and one group 2 (Be, Mg, Ca, Sr, Ba) metal was
      studied by DFT with the hybrid meta-GGA TPSSh functional and the def2-QZVPP basis
      set, selected after screening a number of functional-basis set combinations using
      the AuAE species as benchmark. Dissociation energies, internuclear distances,
      vibrational frequencies, and anharmonic constants were determined for the CuAE
      and AgAE species and their thermal functions evaluated therefrom. On this basis,
      a thermodynamic evaluation of the formation of these species was carried out
      under various conditions.

PMID- 22583287
TI  - Structural and spectroscopic study of the van der Waals complex of CO with HCO+
      and the isoelectronic complex of CS with HCS+.
AB  - This work reports the results of high level ab initio calculations of the OC
      HCO(+) complex and the SC-HCS(+) complex and their hydrogen migration transition
      states. Geometry optimizations are performed at the CCSD(T)/aug-cc-pV5Z level of
      theory. Subsequent frequency calculations are carried out at the CCSD(T)/aug-cc
      pVQZ level of theory. Additional geometry optimizations and harmonic frequency
      calculations for all the species involved in this study have been done with the
      explicitly correlated CCSD(T)-F12 method with the aug-cc-pVTZ and VTZ-F12 basis
      set. The geometries, rotational constants, harmonic vibrational frequencies, and
      energetics of the species involved in the complex are reported. These methods
      result in accurate computational predictions that have mean deviations for bond
      lengths, rotational constants, and vibrational frequencies of 0.001 A, 163 MHz,
      and 46 cm(-1), respectively. These results provide essential spectroscopic
      properties for the complexes that can facilitate both laboratory and interstellar
      observations, and they also provide a comparison between oxygen and sulfur
      complex observability based on thermodynamic stability.

PMID- 22583288
TI  - Electron impact total cross section for acetylene over an extensive range of
      impact energies (1 eV-5000 eV).
AB  - Comprehensive study on electron impact for acetylene molecule is performed in
      terms of eigenphase diagram, electronic excitation cross sections as well as
      total cross section calculations from 1 eV to 5000 eV in this article.
      Computation of cross section over such a wide range of energy is reported for the
      first time. We have employed two distinct formalisms to derive cross sections in
      these impact energies. From 1 eV to ionization threshold of the target we have
      used the ab initio R-matrix method and then spherical complex optical potential
      method beyond that. At the crossing point of energy, both theories matched quite
      well and hence prove that they are consistent with each other. The results
      presented here expectedly give excellent agreement with other experimental values
      and theories available. The techniques employed here are well established and can
      be used to predict cross sections for other targets where data are scarce or not
      available. Also, this methodology may be integrated to online database such as
      Virtual Atomic and Molecular Data Centre to provide cross section data required
      by any user.

PMID- 22583289
TI  - The absorption spectrum of D2: ultrasensitive cavity ring down spectroscopy of
      the (2-0) band near 1.7 MUm and accurate ab initio line list up to 24,000 cm(-1).
AB  - Eleven very weak electric quadrupole transitions Q(2), Q(1), S(0)-S(8) of the
      first overtone band of D(2) have been measured by very high sensitivity CW-cavity
      ring down spectroscopy (CRDS) between 5850 and 6720 cm(-1). The noise equivalent
      absorption of the recordings is on the order of alpha(min) ~ 3 * 10(-11) cm(-1).
      By averaging a high number of spectra, the noise level was lowered to alpha(min)
      ~ 4 * 10(-12) cm(-1) in order to detect the S(8) transition which is among the
      weakest transitions ever detected in laboratory experiments (line intensity on
      the order of 1.8 * 10(-31) cm/molecule at 296 K). A Galatry profile was used to
      reproduce the measured line shape and derive the line strengths. The pressure
      shift and position at zero pressure limit were determined from recordings with
      pressures ranging between 10 and 750 Torr. A highly accurate theoretical line
      list was constructed for pure D(2) at 296 K. The intensity threshold was fixed to
      a value of 1 * 10(-34) cm/molecule at 296 K. The obtained line list is provided
      as supplementary material. It extends up to 24,000 cm(-1) and includes 201
      transitions belonging to ten v-0 cold bands (v = 0-9) and three v-1 hot bands (v
      = 1-3). The energy levels include the relativistic and quantum electrodynamic
      corrections as well as the effects of the finite nuclear mass. The quadrupole
      transition moments are calculated using highly accurate adiabatic wave functions.
      The CRDS line positions and intensities of the first overtone band are compared
      to the corresponding calculated values and to previous measurements of the S(0)
      S(3) lines. The agreement between the CRDS and theoretical results is found
      within the claimed experimental uncertainties (on the order of 1 * 10(-3) cm(-1)
      and 2% for the positions and intensities, respectively) while the previous S(0)
      S(3) measurements showed important deviations for the line intensities.

PMID- 22583290
TI  - A product branching ratio controlled by vibrational adiabaticity and variational
      effects: kinetics of the H + trans-N2H2 reactions.
AB  - The abstraction and addition reactions of H with trans-N(2)H(2) are studied by
      high-level ab initio methods and density functional theory. Rate constants were
      calculated for these two reactions by multistructural variational transition
      state theory with multidimensional tunneling and including torsional
      anharmonicity by the multistructural torsion method. Rate constants of the
      abstraction reaction show large variational effects, that is, the variational
      transition state yields a smaller rate constant than the conventional transition
      state; this results from the fact that the variational transition state has a
      higher zero-point vibrational energy than the conventional transition state. The
      addition reaction has a classical barrier height that is about 1 kcal/mol lower
      than that of the abstraction reaction, but the addition rates are lower than the
      abstraction rates due to vibrational adiabaticity. The calculated branching ratio
      of abstraction to addition is 3.5 at 200 K and decreases to 1.2 at 1000 K and
      1.06 at 1500 K.

PMID- 22583291
TI  - Electronic spectra of the jet-cooled 1-methylvinylthio radical.
AB  - Electronic spectra of the B-X transition of the 1-methylvinylthio radical were
      observed in a discharged jet of propylene sulfide by laser-induced fluorescence
      spectroscopy. Identification of the spectral carrier was made by comparing the
      observed spectra with results of molecular orbital calculations, in particular,
      for vibrational frequencies, rotational contour simulations, and the Franck
      Condon simulations. Vibrational structures observed in the electronic spectra
      indicate that the 1-methylvinylthio radical can be regarded as a molecule with
      C(s) symmetry at the zero-point levels of both the excited and ground states.

PMID- 22583292
TI  - Probing the structural and electronic properties of Ag(n)H(-) (n = 1-3) using
      photoelectron imaging and theoretical calculations.
AB  - Structural and electronic properties of silver hydride cluster anions (Ag(n)H(-);
      n = 1-3) have been explored by combining the negative ion photoelectron imaging
      spectroscopy and theoretical calculations. The photoelectron spectrum of AgH(-)
      exhibits transitions from AgH(- 2)Sigma(+) to AgH (1)Sigma(+) and AgH
      (3)Sigma(+), with the electron affinity (EA) 0.57(3) eV. For Ag(2)H(-), the only
      observed transition is from Ag(2)H(-) (C(infinityv)) (1)Sigma(+) to Ag(2)H
      (C(2v)) (2)A(') and the electron affinity is 2.56(5) eV. Two obvious electron
      bands are observed in photoelectron imaging of Ag(3)H(-), which are assigned to
      the transitions from Ag(3)H(-) (C(2v)-T, which means C(2v) geometry with top site
      hydrogen) (2)B(2) to Ag(3)H (C(2v)-T) (1)A(1) and Ag(3)H (C(2v)-T) (3)B(2). The
      electron affinity is determined to be 1.61(9) eV. The Ag-H stretching modes in
      the ground states of AgH and Ag(2)H are experimentally resolved and their
      frequencies are measured to be 1710(80) and 1650(100) cm(-1), respectively. Aside
      from the above EAs and the vibrational frequencies, the vertical detachment
      energies to all ground states and some excited states of Ag(n)H (n = 1-3) are
      also obtained. Theoretical calculations reproduce the experimental energies quite
      well, and the results are used to assign the geometries and electronic states for
      all related species.

PMID- 22583293
TI  - Electron impact excitation of the a (3)B(1u) electronic state in C2H4: an
      experimentally benchmarked system?
AB  - We report on differential and integral cross section measurements for the
      electron impact excitation of the lowest-lying triplet electronic state (a
      (3)B(1u)) in ethylene (C(2)H(4)). The energy range of the present experiments was
      9 eV-50 eV, with the angular range of the differential cross section measurements
      being 15 degrees -90 degrees . As the ground electronic state of C(2)H(4) is a
      (1)A(g) state, this singlet -> triplet excitation process is expected to be
      dominated by exchange scattering. The present angular distributions are found to
      support that assertion. Comparison, where possible, with previous experimental
      results from the University of Fribourg group shows very good agreement, to
      within the uncertainties on the measured cross sections. Agreement with the
      available theories, however, is generally marginal with the theories typically
      overestimating the magnitude of the differential cross sections. Notwithstanding
      that, the shapes of the theoretical angular distributions were in fact found to
      be in good accord with the corresponding experimental results.

PMID- 22583294
TI  - Attraction between like-charged monovalent ions.
AB  - Ions with like-charges repel each other with a magnitude given by the Coulomb
      law. The repulsion is also known to persist in aqueous solutions albeit factored
      by the medium's dielectric constant. In this paper, we report results from
      molecular dynamics simulations of alkali halides salt solutions indicating an
      effective attraction between some of the like-charged monovalent ions. The
      attraction is observed between anions, as well as between cations, leading to the
      formation of dimers with lifetimes on the order of few picoseconds. Two
      mechanisms have been identified to drive this counterintuitive attraction. The
      first is exhibited by high-charge density ions, such as fluoride, at low salt
      concentrations, yielding effective attractions with magnitude up to the order of
      1-2 kT. In this case, the stronger local electric field generated when the two
      ions are in contact augments the alignment of neighboring waters toward the ions.
      This results in a gain of substantial favorable ion-water interaction energy. For
      fluorides, this interaction constitutes the major change among the different
      energy components compensating for the anion-anion repulsion, and therefore,
      rendering like-charge association possible. The second mechanism involves
      mediation by counterions, the attractions increase with salt concentration and
      are characterized by small magnitudes. In particular, clusters of ion triplets,
      in which a counterion is either bridging the two like-charged ions or is paired
      to only one of them, are formed. Although these two mechanisms may not yield net
      attractions in many cases, they might still be operational and significant,
      explaining effective repulsions between like-charged ions with magnitudes much
      smaller than expected based on continuum electrostatics.

PMID- 22583295
TI  - Nuclear spin optical rotation and Faraday effect in gaseous and liquid water.
AB  - Nuclear spin optical rotation (NSOR) of linearly polarized light, due to the
      nuclear spins through the Faraday effect, provides a novel probe of molecular
      structure and could pave the way to optical detection of nuclear magnetization.
      We determine computationally the effects of the liquid medium on NSOR and the
      Verdet constant of Faraday rotation (arising from an external magnetic field) in
      water, using the recently developed theory applied on a first-principles
      molecular dynamics trajectory. The gas-to-liquid shifts of the relevant
      antisymmetric polarizability and, hence, NSOR magnitude are found to be -14% and 
      29% for (1)H and (17)O nuclei, respectively. On the other hand, medium effects
      both enhance the local electric field in water and, via bulk magnetization, the
      local magnetic field. Together these two effects partially cancel the solvation
      influence on the single-molecular property. We find a good agreement for the
      hydrogen NSOR with a recent pioneering experiment on H(2)O(l).

PMID- 22583296
TI  - Charge localization in multiply charged clusters and their electrical properties:
      some insights into electrospray droplets.
AB  - The surface composition of charged Lennard-Jones clusters A(N) (n+), composed of
      N particles (55 <= N <= 1169) among which n are positively charged with charge q,
      thus having a net total charge Q = nq, is investigated by Monte Carlo with
      Parallel Tempering simulations. At finite temperature, the surface sites of these
      charged clusters are found to be preferentially occupied by charged particles
      carrying large charges, due to Coulombic repulsions, but the full occupancy of
      surface sites is rarely achieved for clusters below the stability limit defined
      in this work. Large clusters (N = 1169) follow the same trends, with a smaller
      propensity for positive particles to occupy the cluster surface at non-zero
      temperature. We show that these charged clusters rather behave as electrical
      spherical conductors for the smaller sizes (N <= 147) but as spheres uniformly
      charged in their volume for the larger sizes (N = 1169).

PMID- 22583297
TI  - How dominant is the most efficient pathway through the potential energy landscape
      of a slowly diffusing disordered system?
AB  - It has been suggested that the most-efficient pathway taken by a slowly diffusing
      many-body system is its geodesic path through the parts of the potential energy
      landscape lying below a prescribed value of the potential energy. From this
      perspective, slow diffusion occurs just because these optimal paths become
      particularly long and convoluted. We test this idea here by applying it to
      diffusion in two kinds of well-studied low-dimensional percolation problems: the
      2d overlapping Lorentz model, and square and simple-cubic bond-dilute lattices.
      Although the most efficient path should be at its most dominant with the high
      dimensional landscapes associated with many-body problems, it is useful to
      examine simpler, low-dimensional, constant-potential-energy problems such as
      these ones, both because the simpler models lend themselves to more accurate
      geodesic-path-finding approaches, and because they offer a significant contrast
      to many of the models used in the traditional energy-landscape literature.
      Neither the continuum nor the lattice percolation examples are adequately
      described by our geodesic-path formalism in the weakly disordered (relatively
      fast-diffusion) limit, but in both cases the formalism successfully predicts the
      existence of the percolation transition and (to a certain extent) the slow
      diffusion characteristic of near-percolation behavior. The numerical results for
      these models are not nearly accurate enough near their transitions to describe
      critical exponents, but the models do showcase the qualitative validity of the
      geodesic perspective in that they allow us to see explicitly how tortuous and
      sparse the optimal pathways become as the diffusion constants begin to vanish.

PMID- 22583298
TI  - Fourth virial coefficients of asymmetric nonadditive hard-disk mixtures.
AB  - The fourth virial coefficient of asymmetric nonadditive binary mixtures of hard
      disks is computed with a standard Monte Carlo method. Wide ranges of size ratio
      (0.05 <= q <= 0.95) and nonadditivity (-0.5 <= Delta <= 0.5) are covered. A
      comparison is made between the numerical results and those that follow from some
      theoretical developments. The possible use of these data in the derivation of new
      equations of state for these mixtures is illustrated by considering a rescaled
      virial expansion truncated to fourth order. The numerical results obtained using
      this equation of state are compared with Monte Carlo simulation data in the case
      of a size ratio q = 0.7 and two nonadditivities Delta = +/-0.2.

PMID- 22583299
TI  - Semiclassical approach to model quantum fluids using the statistical associating
      fluid theory for systems with potentials of variable range.
AB  - Thermodynamic properties of quantum fluids are described using an extended
      version of the statistical associating fluid theory for potentials of variable
      range (SAFT-VR) that takes into account quantum corrections to the Helmholtz free
      energy A, based on the Wentzel-Kramers-Brillouin approximation. We present the
      theoretical background of this approach (SAFT-VRQ), considering two different
      cases depending on the continuous or discontinuous nature of the particles pair
      interaction. For the case of continuous potentials, we demonstrate that the
      standard Wigner-Kirkwood theory for quantum fluids can be derived from the de
      Broglie-Bohm formalism for quantum mechanics that can be incorporated within the
      Barker and Henderson perturbation theory for liquids in a straightforward way.
      When the particles interact via a discontinuous pair potential, the SAFT-VR
      method can be combined with the perturbation theory developed by Singh and Sinha
      [J. Chem. Phys. 67, 3645 (1977); and ibid. 68, 562 (1978)]. We present an
      analytical expression for the first-order quantum perturbation term for a square
      well potential, and the theory is applied to model thermodynamic properties of
      hydrogen, deuterium, neon, and helium-4. Vapor-liquid equilibrium, liquid and
      vapor densities, isochoric and isobaric heat capacities, Joule-Thomson
      coefficients and inversion curves are predicted accurately with respect to
      experimental data. We find that quantum corrections are important for the global
      behavior of properties of these fluids and not only for the low-temperature
      regime. Predictions obtained for hydrogen compare very favorably with respect to
      cubic equations of state.

PMID- 22583300
TI  - Physics of shell assembly: line tension, hole implosion, and closure catastrophe.
AB  - The self-assembly of perfectly ordered closed shells is a challenging process
      involved in many biological and nanoscale systems. However, most of the aspects
      that determine their formation are still unknown. Here we investigate the growth
      of shells by simulating the assembly of spherical structures made of N identical
      subunits. Remarkably, we show that the formation and energetics of partially
      assembled shells are dominated by an effective line-tension that can be described
      in simple thermodynamic terms. In addition, we unveil two mechanisms that can
      prevent the correct formation of defect-free structures: "hole implosion," which
      leads to a premature closure of the shell; and "closure catastrophe," which
      causes a dramatic production of structural disorder during the later stages of
      the growth of big shells.

PMID- 22583301
TI  - Beyond power laws: a new approach for analyzing single molecule photoluminescence
      intermittency.
AB  - The photoluminescence intermittency (PI) exhibited by single emitters has been
      studied for over a decade. To date, the vast majority of PI analyses involve
      parsing the data into emissive and non-emissive events, constructing histograms
      of event durations, and fitting these histograms to either exponential or power
      law probability distributions functions (PDFs). Here, a new method for analyzing
      PI data is presented where the data are used directly to construct a cumulative
      distribution function (CDF), and maximum-likelihood estimation techniques are
      used to determine the best fit of a model PDF to the CDF. Statistical tests are
      then employed to quantitatively evaluate the hypothesis that the CDF (data) is
      represented by the model PDF. The analysis method is outlined and applied to PI
      exhibited by single CdSe/CdS core-shell nanocrystals and the organic chromophore
      violamine R isolated in single crystals of potassium-acid phthalate. Contrary to
      previous studies, the analysis presented here demonstrates that the PI exhibited
      by these systems is not described by a power law. The analysis developed here is
      also used to quantify heterogeneity within PI data obtained from a collection of
      CdSe/CdS nanocrytals, and for the determination of statistically significant
      changes in PI accompanying perturbation of the emitter. In summary, the analysis
      methodology presented here provides a more statistically robust approach for
      analyzing PI data.

PMID- 22583302
TI  - Constrained dynamics of localized excitations causes a non-equilibrium phase
      transition in an atomistic model of glass formers.
AB  - Recent progress has demonstrated that trajectory space for both kinetically
      constrained lattice models and atomistic models can be partitioned into a liquid
      like and an inactive basin with a non-equilibrium phase transition separating
      these behaviors. Recent work has also established that excitations in atomistic
      models have statistics and dynamics like those in a specific class of kinetically
      constrained models. But it has not been known whether the non-equilibrium phase
      transitions occurring in the two classes of models have similar origins. Here, we
      show that the origin is indeed similar. In particular, we show that the number of
      excitations identified in an atomistic model serves as the order parameter for
      the inactive-active phase transition for that model. In this way, we show that
      the mechanism by which excitations are correlated in an atomistic model - by
      dynamical facilitation - is the mechanism from which the active-inactive phase
      transition emerges. We study properties of the inactive phase and show that it is
      amorphous lacking long-range order. We also discuss the choice of dynamical order
      parameters.

PMID- 22583303
TI  - Temperature dependence of fluid transport in nanopores.
AB  - Understanding the temperature-dependent nanofluidic transport behavior is
      critical for developing thermomechanical nanodevices. By using non-equilibrium
      molecular dynamics simulations, the thermally responsive transport resistance of
      liquids in model carbon nanotubes is explored as a function of the nanopore size,
      the transport rate, and the liquid properties. Both the effective shear stress
      and the nominal viscosity decrease with the increase of temperature, and the
      temperature effect is coupled with other non-thermal factors. The molecular-level
      mechanisms are revealed through the study of the radial density profile and
      hydrogen bonding of confined liquid molecules. The findings are verified
      qualitatively with an experiment on nanoporous carbon.

PMID- 22583304
TI  - Grand canonical-like molecular dynamics simulations: application to anisotropic
      mass diffusion in a nanoporous medium.
AB  - In this work, we describe two grand canonical-like molecular dynamics approaches
      to investigate mass diffusion phenomenon of a simple Lennard-Jones fluid confined
      between solid surfaces and in direct contact with reservoirs. In the first
      method, the density is used as the control variable in the reservoir whereas it
      is the pressure in the second method. Both methods provide consistent results,
      however, the constant density approach is the most efficient with respect to the
      computational time and implementation. Then, employing the constant density
      approach, we have studied the transient behavior of the diffusion process
      associated with the migration of one fluid into another one confined between
      parallel solid walls. Results have shown that the evolution of molar fraction of
      the invading fluid follows roughly a 1D diffusion model when the solid phase is
      weakly or moderately adsorbent with a characteristic time increasing when the
      pore width decreases. However, when the adsorption is high and the pore width
      small (i.e., below ten molecular sizes), the apparent mass diffusion in the
      adsorbed layer is reduced compared to that in the center of the slit pore. Hence,
      this mass diffusion process becomes a two-dimension phenomenon that must take
      into account an effective mass diffusion coefficient varying locally.

PMID- 22583305
TI  - Distance dependent quenching effect in nanoparticle dimers.
AB  - In this paper, we investigate the emission characteristics of a molecule placed
      in the gap of a nanoparticle dimer configuration. The emission process is
      described in terms of a local field enhancement factor and the overall quantum
      yield of the system. The molecule is represented as a dipolar source, with fixed
      length and fed by a constant current. We first describe the coupled dimer
      molecule system and compare these results to a single sphere-molecule system.
      Next, the effect of dimer size is investigated by changing the radius of the
      nanoparticles. We find that when the radius increases, a saturation effect occurs
      that trends towards the case of a radiating dipole between two flat interfaces,
      which we refer to as a parallel plate waveguide geometry. An analytical solution
      for the parallel plate waveguide geometry is presented and compared to the
      results for the spherical dimer configuration. We use this approximation as a
      reference solution, and also, it provides useful guidelines to understand the
      physical mechanism behind the energy transfer between the molecule and the dimer.
      We find that the emission intensity undergoes a quenching effect only when the
      inter-nanoparticle gap distance of the dimer is very small, meaning that strong
      coupling prevails over energy engaged in the heating process unless the molecule
      is extremely close to the metal surface.

PMID- 22583306
TI  - Dual conductance, negative differential resistance, and rectifying behavior in a
      molecular device modulated by side groups.
AB  - We investigate the electronic transport properties for a molecular device model
      constructed by a phenylene ethynylene oligomer molecular with different side
      groups embedding in a carbon chain between two graphene electrodes. Using the
      first-principles method, the unusual dual conductance, negative differential
      resistance (NDR) behavior with large peak to valley ratio, and obvious rectifying
      performance are numerically observed in such proposed molecular device. The
      analysis of the molecular projected self-consistent Hamiltonian and the evolution
      of the frontier molecular orbitals (MOs) as well as transmission coefficients
      under various external voltage biases gives an inside view of the observed
      results, which suggests that the dual conductance behavior and rectifying
      performance are due to the asymmetry distribution of the frontier MOs as well as
      the corresponding coupling between the molecule and electrodes. But the NDR
      behavior comes from the conduction orbital being suppressed at certain bias.
      Interestingly, the conduction properties can be tuned by introducing side groups
      to the molecule and the rectification as well as the NDR behavior (peak to valley
      ratio) can be improved by adding different side groups in the device model.

PMID- 22583307
TI  - Enhanced charge transfer by phenyl groups at a rubrene/C60 interface.
AB  - Exciton dynamics at an interface between an electron donor, rubrene, and a C(60)
      acceptor is studied by nonadiabatic quantum molecular dynamics simulation.
      Simulation results reveal an essential role of the phenyl groups in rubrene in
      increasing the charge-transfer rate by an order-of-magnitude. The atomistic
      mechanism of the enhanced charge transfer is found to be the amplification of
      aromatic breathing modes by the phenyl groups, which causes large fluctuations of
      electronic excitation energies. These findings provide insight into molecular
      structure design for efficient solar cells, while explaining recent experimental
      observations.

PMID- 22583308
TI  - Interplay between intrachain and interchain interactions in semiconducting
      polymer assemblies: the HJ-aggregate model.
AB  - A new model for analyzing the photophysics of polymer aggregates is introduced
      taking into account exciton motion along a polymer chain and across polymer
      chains. Excitonic coupling and vibronic coupling are treated on equal footing
      using a Holstein-based Hamiltonian represented in a multi-particle basis set. In
      the HJ-aggregate model the competition between intrachain (through-bond) coupling
      leading to Wannier-Mott excitons, and interchain (through-space) coupling leading
      to Frenkel excitons, is studied in detail for two model dimers: one composed of
      red-phase polydiacetylene (PDA) chains and the other composed of regioregular
      P3HT chains. The resulting photophysical properties are shown to depend
      critically on the relative magnitudes of the intrachain and interchain exciton
      bandwidths. Dominant intraband (interband) coupling favors a photophysical
      response resembling J-aggregates (H-aggregates). In PDA dimers, where intrachain
      coupling prevails, the absorption spectrum is dominated by the 0-0 peak, as is
      characteristic of J-aggregates. The photoluminescence (PL) spectrum displays
      hybrid character: the ratio of the main (0-0) band to the first vibronic sideband
      intensities is initially zero at T = 0 K due to the forbidden nature of the 0-0
      transition, but then increases with temperature in a manner characteristic of H
      aggregates, peaking when kT ~ DeltaE, where DeltaE is the interchain splitting.
      Further increases in temperature result in a decline of the PL ratio, as in a J
      aggregate. This remarkable H to J transition is also predicted for the
      temperature dependence of the radiative decay rate, k(rad). The maximum (peak)
      rate scales as, k(rad) (max)~(W(intra)/W(inter))(1/2), where W(intra) (W(inter))
      is the intrachain (interchain) exciton bandwidth. Hence, when W(intra) is
      sufficiently larger than W(inter) the dimer displays thermally activated
      superradiance. In P3HT the intrachain coupling is far weaker than in PDA making
      the intrachain and interchain couplings comparable in the crystalline phase.
      Although the absorption spectral line shape is still well-accounted for by the
      conventional H-aggregate model, the photoluminescence is more sensitive, with H
      or J behavior tunable by changes in morphology. Long range intrachain order which
      coincides with weaker interchain interactions induces J-aggregate behavior, while
      short range intrachain order and the resulting stronger interchain coupling
      induces H-aggregate behavior. Our predictions neatly account for the H-like
      dominance exhibited by the PL from spin-cast films and the J-like dominance
      exhibited by the PL from highly ordered P3HT nanofibers self-assembled in
      toluene.

PMID- 22583309
TI  - Distribution of transverse chain fluctuations in harmonically confined
      semiflexible polymers.
AB  - Two different experimental studies of polymer dynamics based on single-molecule
      fluorescence imaging have recently found evidence of heterogeneities in the
      widths of the putative tubes that surround filaments of F-actin during their
      motion in concentrated solution. In one [J. Glaser, D. Chakraborty, K. Kroy, I.
      Lauter, M. Degawa, N. Kirchesner, B. Hoffmann, R. Merkel, and M. Giesen, Phys.
      Rev. Lett. 105, 037801 (2010)], the observations were explained in terms of the
      statistics of a worm-like chain confined to a potential determined self
      consistently by a binary collision approximation, and in the other [B. Wang, J.
      Guan, S. M. Anthony, S. C. Bae, K. S. Schweizer, and S. Granick, Phys. Rev. Lett.
      104, 118301 (2010)], they were explained in terms of the scaling properties of a
      random fluid of thin rods. In this paper, we show, using an exact path integral
      calculation, that the distribution of the length-averaged transverse fluctuations
      of a harmonically confined weakly bendable rod (one possible realization of a
      semiflexible chain in a tube), is in good qualitative agreement with the
      experimental data, although it is qualitatively different in analytic structure
      from the earlier theoretical predictions. We also show that similar path integral
      techniques can be used to obtain an exact expression for the time correlation
      function of fluctuations in the tube cross section.

PMID- 22583310
TI  - From A to B: a ride in the free energy surfaces of protein G domains suggests how
      new folds arise.
AB  - Metamorphic proteins are an extremely intriguing case of protein evolution and a
      golden opportunity to challenge the current simplified models. In a recent work,
      we showed that a coarse-grained Go model can be used to study the thermodynamics
      of lymphotactin, a naturally occurring metamorphic protein. Here, we extend such
      model by including the necessary atomic detail to study the effects of the single
      mutations that artificially bring the GA domain of protein G to fold into the GB
      domain of the same protein. The results of this all-atom Go model show how the
      residual structure of the denatured state is an early indicator of a forthcoming
      fold and function switch. These findings reconcile the results of previous
      studies on similar systems highlighting the different role played by secondary
      and tertiary interactions and suggesting a possible way for new folds to arise.

PMID- 22583311
TI  - Polar solvation dynamics of lysozyme from molecular dynamics studies.
AB  - The solvation dynamics of a protein are believed to be sensitive to its secondary
      structures. We have explored such sensitivity in this article by performing room
      temperature molecular dynamics simulation of an aqueous solution of lysozyme.
      Nonuniform long-time relaxation patterns of the solvation time correlation
      function for different segments of the protein have been observed. It is found
      that relatively slower long-time solvation components of the alpha-helices and
      beta-sheets of the protein are correlated with lower exposure of their polar
      probe residues to bulk solvent and hence stronger interactions with the
      dynamically restricted surface water molecules. These findings can be verified by
      appropriate experimental studies.

PMID- 22583312
TI  - Dynamics of polymer translocation into a circular nanocontainer through a
      nanopore.
AB  - Using Langevin dynamics simulations, we investigate the dynamics of polymer
      translocation into a circular nanocontainer through a nanopore under a driving
      force F. We observe that the translocation probability initially increases and
      then saturates with increasing F, independent of phi, which is the average
      density of the whole chain in the nanocontainer. The translocation time
      distribution undergoes a transition from a Gaussian distribution to an asymmetric
      distribution with increasing phi. Moreover, we find a nonuniversal scaling
      exponent of the translocation time as chain length, depending on phi and F. These
      results are interpreted by the conformation of the translocated chain in the
      nanocontainer and the time of an individual segment passing through the pore
      during translocation.

PMID- 22583313
TI  - Note: gas phase structures of bare Si8 and Si11 clusters from molecular beam
      electric deflection experiments.

PMID- 22583315
TI  - Social media for message testing: a multilevel approach to linking favorable
      viewer responses with message, producer, and viewer influence on YouTube.
AB  - To explore the feasibility of social media for message testing, this study
      connects favorable viewer responses to antismoking videos on YouTube with the
      videos' message characteristics (message sensation value [MSV] and appeals),
      producer types, and viewer influences (viewer rating and number of viewers).
      Through multilevel modeling, a content analysis of 7,561 viewer comments on
      antismoking videos is linked with a content analysis of 87 antismoking videos.
      Based on a cognitive response approach, viewer comments are classified and coded
      as message-oriented thought, video feature-relevant thought, and audience
      generated thought. The three mixed logit models indicate that videos with a
      greater number of viewers consistently increased the odds of favorable viewer
      responses, while those presenting humor appeals decreased the odds of favorable
      message-oriented and audience-generated thoughts. Some significant interaction
      effects show that videos produced by laypeople may hinder favorable viewer
      responses, while a greater number of viewer comments can work jointly with videos
      presenting threat appeals to predict favorable viewer responses. Also, for a more
      accurate understanding of audience responses to the messages, nuance cues should
      be considered together with message features and viewer influences.

PMID- 22583316
TI  - Effects of lipoprotein-associated phospholipase A2 on arginase/nitric oxide
      pathway in hemodialysis patients.
AB  - Lipoprotein-associated phospholipase A2 (Lp-PLA2) and arginase are recently
      described inflammatory biomarkers associated with cardiovascular disease. In this
      study, we aimed to investigate the possible effects of serum Lp-PLA2 mass levels
      on arginase/nitric oxide (NO) pathway as a cardiovascular risk marker in
      hemodialysis (HD) patients. Forty-three HD patients and 15 healthy subjects were
      included in this study. Lipid profile, high sensitivity C-reactive protein (hs
      CRP), albumin, creatinine, body mass index (BMI), Lp-PLA2 and total nitrite
      levels, and arginase activity were determined in serum samples from patients and
      control subjects. Lp-PLA2 levels were found to be positively correlated with
      arginase, triglycerides, total cholesterol, low-density lipoprotein-cholesterol,
      and age and negatively correlated with high-density lipoprotein-cholesterol and
      total nitrite levels, while there was no correlation with BMI and hs-CRP,
      albumin, and creatinine levels in HD patients. We conclude that elevated Lp-PLA2
      mass levels may contribute to impaired arginase/NO pathway in HD patients and
      that increased the arginase activity and Lp-PLA2 mass levels with decreased total
      nitrite levels seem to be useful biochemical markers in terms of reflecting
      endothelial dysfunction and associated cardiovascular risks in HD patients.

PMID- 22583317
TI  - A novel role for the non-catalytic intracellular domain of Neprilysins in muscle
      physiology.
AB  - BACKGROUND INFORMATION: Neprilysins (Neps) are membrane-bound M13 endopeptidases
      responsible for the activation and/or inactivation of peptide signalling events
      on cell surfaces. By hydrolysing their respective substrates, mammalian Neps are
      crucial to the metabolism of numerous bioactive peptides, especially in the
      nervous, immune, cardiovascular and inflammatory systems. On the basis of their
      involvement in essential physiological processes, proteins of the Nep family
      constitute putative therapeutic agents as well as targets in different diseases,
      including Alzheimer's disease. RESULTS: We here demonstrate that overexpression
      of Neprilysin 4 (Nep4) in Drosophila melanogaster leads to a severe muscle
      degeneration phenotype. This phenotype is observed for overexpression of full
      length Nep4 in somatic muscles and is accompanied by severely impaired movement
      of larvae and lethality in late larval development. On the contrary, down
      regulation of expression caused only the latter two effects. By expressing
      several mutated and truncated forms of Nep4 in transgenic animals, we show that
      the intracellular domain is responsible for the observed phenotypes while
      catalytic activity of the enzyme was apparently dispensable. A yeast two-hybrid
      screen identified a yet uncharacterised carbohydrate kinase as a first
      interaction partner of the intracellular domain of Nep4. CONCLUSIONS: These data
      demonstrate that the physiological significance of Nep4 is not limited to its
      function as an active peptidase but that the enzyme's intracellular N-terminus is
      affecting muscle integrity, independent of the protein's enzymatic activity. To
      our knowledge, this is the first report of an intracellular Nep domain being
      involved in muscle integrity.

PMID- 22583319
TI  - Proposal for a British neurosurgical trainee research collaborative.

PMID- 22583320
TI  - Expanding rare-earth oxidation state chemistry to molecular complexes of
      holmium(II) and erbium(II).
AB  - The first molecular complexes of holmium and erbium in the +2 oxidation state
      have been generated by reducing Cp'(3)Ln [Cp' = C(5)H(4)SiMe(3); Ln = Ho (1), Er
      (2)] with KC(8) in the presence of 18-crown-6 in Et(2)O at -35  degrees C under
      argon. Purification and crystallization below -35  degrees C gave isomorphous
      [(18-crown-6)K][Cp'(3)Ln] [Ln = Ho (3), Er (4)]. The three Cp' ring centroids
      define a trigonal-planar geometry around each metal ion that is not perturbed by
      the location of the potassium crown cation near one ring with K-C(Cp') distances
      of 3.053(8)-3.078(2) A. The metrical parameters of the three rings are
      indistinguishable within the error limits. In contrast to Ln(2+) complexes of Eu,
      Yb, Sm, Tm, Dy, and Nd, 3 and 4 have average Ln-(Cp' ring centroid) distances
      only 0.029 and 0.021 A longer than those of the Ln(3+) analogues 1 and 2, a
      result similar to that previously reported for the 4d(1) Y(2+) complex [(18-crown
      6)K][Cp'(3)Y] (5) and the 5d(1) La(2+) complex [K(18-crown-6)(Et(2)O)][Cp"(3)La]
      [Cp" = 1,3-(Me(3)Si)(2)C(5)H(3)]. Surprisingly, the UV-vis spectra of 3 and 4 are
      also very similar to that of 5 with two broad absorptions in the visible region,
      suggesting that 3-5 have similar electron configurations. Density functional
      theory calculations on the Ho(2+) and Er(2+) species yielded HOMOs that are
      largely 5d(z(2)) in character and supportive of 4f(10)5d(1) and 4f(11)5d(1)
      ground-state configurations, respectively.

PMID- 22583321
TI  - Animal breeding and development--South American perspective.

PMID- 22583322
TI  - Bayesian conjugate analysis using a generalized inverted Wishart distribution
      accounts for differential uncertainty among the genetic parameters--an
      application to the maternal animal model.
AB  - Consider the estimation of genetic (co)variance components from a maternal animal
      model (MAM) using a conjugated Bayesian approach. Usually, more uncertainty is
      expected a priori on the value of the maternal additive variance than on the
      value of the direct additive variance. However, it is not possible to model such
      differential uncertainty when assuming an inverted Wishart (IW) distribution for
      the genetic covariance matrix. Instead, consider the use of a generalized
      inverted Wishart (GIW) distribution. The GIW is essentially an extension of the
      IW distribution with a larger set of distinct parameters. In this study, the GIW
      distribution in its full generality is introduced and theoretical results
      regarding its use as the prior distribution for the genetic covariance matrix of
      the MAM are derived. In particular, we prove that the conditional conjugacy
      property holds so that parameter estimation can be accomplished via the Gibbs
      sampler. A sampling algorithm is also sketched. Furthermore, we describe how to
      specify the hyperparameters to account for differential prior opinion on the
      (co)variance components. A recursive strategy to elicit these parameters is then
      presented and tested using field records and simulated data. The procedure
      returned accurate estimates and reduced standard errors when compared with non
      informative prior settings while improving the convergence rates. In general,
      faster convergence was always observed when a stronger weight was placed on the
      prior distributions. However, analyses based on the IW distribution have also
      produced biased estimates when the prior means were set to over-dispersed values.

PMID- 22583323
TI  - A method for the prediction of multitrait breeding values for use in stochastic
      simulation to compare progeny-testing schemes, with large progeny groups for
      proven sires.
AB  - A method of approximating estimated breeding values (EBV) from a multivariate
      distribution of true breeding values (TBV) and EBV is proposed for use in large
      scale stochastic simulation of alternative breeding schemes with a complex
      breeding goal. The covariance matrix of the multivariate distributions includes
      the additive genetic (co)variances and approximated prediction error
      (co)variances at different selection stages in the life of the animal. The
      prediction error (co)variance matrix is set up for one animal at a time,
      utilizing information on the selection candidate and its offspring, the parents,
      as well as paternal and maternal half- sibs. The EBV are a regression on TBV
      taking individual uncertainty into account, but with additional 'free' variation
      drawn at random. With the current information included in the calculation of the
      prediction error variance of a selection candidate, it is concluded that the
      method can be used to optimize progeny-testing schemes, where the progeny-tested
      sires are utilized with large progeny groups, e.g. through artificial
      insemination.

PMID- 22583324
TI  - Pedigree- and marker-based methods in the estimation of genetic diversity in
      small groups of Holstein cattle.
AB  - Genetic diversity is often evaluated using pedigree information. Currently,
      diversity can be evaluated in more detail over the genome based on large numbers
      of SNP markers. Pedigree- and SNP-based diversity were compared for two small
      related groups of Holstein animals genotyped with the 50 k SNP chip, genome-wide,
      per chromosome and for part of the genome examined. Diversity was estimated with
      coefficient of kinship (pedigree) and expected heterozygosity (SNP). SNP-based
      diversity at chromosome regions was determined using 5-Mb sliding windows, and
      significance of difference between groups was determined by bootstrapping. Both
      pedigree- and SNP-based diversity indicated more diversity in one of the groups;
      26 of the 30 chromosomes showed significantly more diversity for the same group,
      as did 25.9% of the chromosome regions. Even in small populations that are
      genetically close, differences in diversity can be detected. Pedigree- and SNP
      based diversity give comparable differences, but SNP-based diversity shows on
      which chromosome regions these differences are based. For maintaining diversity
      in a gene bank, SNP-based diversity gives a more detailed picture than pedigree
      based diversity.

PMID- 22583325
TI  - Evolution of the genetic variability of eight French dairy cattle breeds assessed
      by pedigree analysis.
AB  - A pedigree analysis was performed on eight French dairy cattle breeds to assess
      their change in genetic variability since a first analysis completed in 1996. The
      Holstein, Normande and Montbeliarde breeds are selected internationally with over
      hundreds of thousands cows registered in the performance recording system. Three
      breeds are internationally selected but with limited numbers of cows in France
      (Brown Swiss, French Simmental and French Red Pied). The last two remaining
      breeds (Abondance and Tarentaise) are raised at regional level. The effective
      numbers of ancestors of cows born between 2004 and 2007 varied between 15
      (Abondance and Tarentaise) and 51 (French Red Pied). The effective population
      sizes (classical approach) varied between 53 (Abondance) and 197 (French Red
      Pied). This article also compares the genetic variability of the ex situ
      (collections of the French National Cryobank) and in situ populations. The
      results were commented in regard to the recent history of gene flows in the
      different breeds as well as the existence of more or less stringent bottlenecks.
      Our results showed that whatever the size of the breeds, their genetic diversity
      impoverished quite rapidly since 1996 and they all could be considered as quite
      poor from a genetic diversity point of view. It shows the need for setting up
      cryobanks as gene reservoirs as well as sustainable breeding programmes that
      include loss of genetic diversity as an integrated control parameter.

PMID- 22583326
TI  - Prioritization based on neutral genetic diversity may fail to conserve important
      characteristics in cattle breeds.
AB  - Conservation of the intraspecific genetic diversity of livestock species requires
      protocols that assess between-breed genetic variability and also take into
      account differences among individuals within breeds. Here, we focus on variation
      between breeds. Conservation of neutral genetic variation has been seen as
      promoting, through linkage processes, the retention of useful and potentially
      useful variation. Using public information on beef cattle breeds, with a total of
      165 data sets each relating to a breed comparison of a performance variable, we
      have tested this paradigm by calculating the correlations between pairwise breed
      differences in performance and pairwise genetic distances deduced from
      biochemical and immunological polymorphisms, microsatellites and single
      nucleotide polymorphisms. As already observed in floral and faunal biodiversity,
      significant positive correlations (n=54) were found, but many correlations were
      non-significant (n=100) or significantly negative (n=11). This implies that
      maximizing conserved neutral genetic variation with current techniques may
      conserve breed-level genetic variation in some traits but not in others and
      supports the view that genetic distance measurements based on neutral genetic
      variation are not sufficient as a determinant of conservation priority among
      breeds.

PMID- 22583327
TI  - Sampling method for estimating neutral allele frequency in a pedigreed
      population.
AB  - The estimated allele frequency at neutral DNA marker loci is a fundamental
      parameter for establishing a conservation scheme for a set of livestock breeds.
      In this study, we propose a novel 'minimum distance (MD) method' for estimating
      neutral allele frequencies, which minimizes the error by the use of pedigree
      information. Using computer simulation and actual microsatellite data for a
      pedigreed cattle population, the performance of the proposed method was compared
      with that of conventional random sampling (RND). MD manifests a promising
      superiority to RND, irrespective of the sample size and the depth of pedigree. It
      is theoretically demonstrated that the error of the estimates depends on both the
      sample size and the distance of founder allele frequencies between the sampled
      and the non-sampled individuals. MD samples individuals so as to minimize the
      latter source of estimation error.

PMID- 22583328
TI  - Effects of a 10-year conservation programme on the genetic diversity of the
      Pottoka pony--new clues regarding their origin.
AB  - Here, we present the results of a genetic analysis of 463 Pottoka ponies
      corresponding to four generations, using 17 microsatellite markers. Ten years
      after the beginning of the Pottoka conservation programme, the values for the
      genetic diversity of the breed are still high and stable, indicating the success
      of the programme. We found null alleles in Pottoka for the ASB23, HMS3 and HTG10
      microsatellites. Together with information obtained from other pony breeds from
      the Iberian Peninsula, this finding indicates that these microsatellites should
      not be used for phylogenetic analyses or parentage tests, at least for these
      breeds. The high heterozygosity exhibited by this breed in comparison to other
      ponies, together with its genetic proximity to the centroid of the allele
      frequencies, suggest that Pottoka allele frequencies are close to those initially
      exhibited by the ancestors of current European ponies. The results obtained in
      the current work, together with results from previous studies of ponies and
      horses from the Iberian Peninsula, corroborate the idea of a unique origin of all
      ponies from the European Atlantic Area. In contrast, our results do not
      corroborate the idea that these are derived from a domestication event in the
      Iberian Peninsula, nor that they have incorporated ancient Iberian horse genes
      into their genetic pool to a larger extent than other horse breeds.

PMID- 22583329
TI  - Community-based alternative breeding plans for indigenous sheep breeds in four
      agro-ecological zones of Ethiopia.
AB  - Based on the results of participatory approaches to define traits in the breeding
      objectives, four scenarios of ram selection and ram use were compared via
      deterministic modelling of breeding plans for community-based sheep breeding
      programmes in four diverse agro-ecological regions of Ethiopia. The regions (and
      production systems) were Afar (pastoral/agro-pastoral), Bonga and Horro (both
      mixed crop-livestock) and Menz (sheep-barley). The schemes or scenarios differed
      in terms of selection intensity and duration of ram use. The predicted genetic
      gains per year in yearling weight (kilograms) were comparable across the schemes
      but differed among the breeds and ranged from 0.399 to 0.440 in Afar, 0.813 to
      0.894 in Bonga, 0.850 to 0.940 in Horro, and 0.616 to 0.699 in Menz. The genetic
      gains per year in number of lambs born per ewe bred ranged from 0.009 to 0.010 in
      both Bonga and Horro. The predicted genetic gain in the proportion of lambs
      weaned per ewe joined was nearly comparable in all breeds ranging from 0.008 to
      0.011. The genetic gain per year in milk yield of Afar breed was in the order of
      0.018 to 0.020 kg, while the genetic gain per generation for greasy fleece weight
      (kg) ranged from 0.016 to 0.024 in Menz. Generally, strong selection and shorter
      duration of ram use for breeding were the preferred options. The expected genetic
      gains are satisfactory but largely rely on accurate and continuous pedigree and
      performance recording.

PMID- 22583331
TI  - Sodium glucose co-transporter 2 (SGLT2) inhibitors: novel antidiabetic agents.
AB  - INTRODUCTION: Maintenance of glucose homeostasis in healthy individuals involves
      SGLT2 (sodium glucose co-transporter 2)-mediated recovery of glucose from the
      glomerular filtrate which otherwise would be excreted in urine. Clinical studies
      indicate that SGLT2 inhibitors provide an insulin-independent means to reduce the
      hyperglycemia that is the hallmark of type 2 diabetes mellitus (T2DM) with
      minimal risk of hypoglycemia. AREAS COVERED: The pharmacophore common to the
      SGLT2 inhibitors currently in development is a diarylmethane C-glucoside which is
      discussed in this review. The focus is how this pharmacophore was further
      modified as inferred from the patents publishing from 2009 to 2011. The emphasis
      is on the strategy that each group employed to circumvent the constraints imposed
      by prior art and how the resulting SGLT2 potency and selectivity versus SGLT1
      compared with that of the lead clinical compound dapagliflozin. EXPERT OPINION:
      SGLT2 inhibitors offer a new fundamentally different approach for treatment of
      diabetes. To date, the clinical results suggest that for non-renally impaired
      patients this class of inhibitors could be safely used at any stage of T2DM
      either alone or in combination with other marketed antidiabetic medications.

PMID- 22583332
TI  - Androgen receptor antagonists: a patent review (2008-2011).
AB  - INTRODUCTION: Androgen receptor (AR) antagonists are predominantly used as
      chemical castration to treat prostate cancer (i.e., in conjunction with androgen
      deprivation therapy (ADT)). Unfortunately, castration-resistant prostate cancer
      (CRPC) typically develops that is refractory to targeted therapy. Insights into
      CRPC biology have led to the emergence of a promising clinical candidate MDV3100
      (1) and a resurgence in this field. A pipeline of preclinical competitive (C
      terminally directed) antagonists was discovered using a variety of innovative
      screening paradigms. Some inhibit nuclear translocation, selectively downregulate
      or degrade AR (SARD), antagonize wild-type and escape mutant AR (pan-antagonists)
      and/or antagonize AR target organs in vivo. Separately, the N-terminal domain has
      emerged as a promising novel target for noncompetitive antagonists. AREAS
      COVERED: AR antagonists whose patents published between 2008 and 2011 are
      reviewed. Antagonists are organized based on the screening paradigm reported as
      discussed above. EXPERT OPINION: Novel mechanisms provide a more informed basis
      for selecting a competitive antagonist; however, high potency and favorable in
      vivo properties remain paramount. Noncompetitive antagonists have theoretical
      advantages suggestive of improved clinical efficacy, but no clinical proof of
      concept as of yet.

PMID- 22583333
TI  - Protein-bound water as the determinant of asymmetric functional conversion
      between light-driven proton and chloride pumps.
AB  - Bacteriorhodopsin (BR) and halorhodopsin (HR) are light-driven outward proton and
      inward chloride pumps, respectively. They have similar protein architecture,
      being composed of seven-transmembrane helices that bind an all-trans-retinal. BR
      can be converted into a chloride pump by a single amino acid replacement at
      position 85, suggesting that BR and HR share a common transport mechanism, and
      the ionic specificity is determined by the amino acid at that position. However,
      HR cannot be converted into a proton pump by the corresponding reverse mutation.
      Here we mutated 6 and 10 amino acids of HR into BR-like, whereas such multiple HR
      mutants never pump protons. Light-induced Fourier transform infrared spectroscopy
      revealed that hydrogen bonds of the retinal Schiff base and water are both strong
      for BR and both weak for HR. Multiple HR mutants exhibit strong hydrogen bonds of
      the Schiff base, but the hydrogen bond of water is still weak. We concluded that
      the cause of nonfunctional conversion of HR is the lack of strongly hydrogen
      bonded water, the functional determinant of the proton pump.

PMID- 22583334
TI  - Living donor liver transplantation from an asymptomatic mother who was a carrier
      for ornithine transcarbamylase deficiency.
AB  - Liver transplantation (LT) has been adopted as a radical treatment for ornithine
      transcarbamylase deficiency (OTCD), yielding favorable outcomes. Despite the fact
      that it is an inheritable disease, a blood relative who is heterozygous for the
      disorder must sometimes be used as a liver donor for living donor LT. There is
      ongoing discussion regarding the use of heterozygous donors, however, to our
      knowledge, no cases where donation was determined based on the Ornithine
      transcarbamylase (OTC) activity before LT have been reported. Between May 2001
      and April 2011, 17 patients were indicated for living donor LT because of OTCD at
      our facility. There were three cases with heterozygous donor candidate (17.6%).
      All heterozygous candidates underwent a liver biopsy to measure their OTC
      activity before LT and made efforts to secure the safety of the both donor and
      recipient. Two of 3 candidates had headaches sometimes, and their activity was
      less than 40%, and thus they were not employed as the donor. One candidate with
      104.4% activity was employed, yielding favorable outcomes. Our current experience
      supported the effectiveness of our donation criteria, however it is necessary to
      collect sufficient data on a large number of patients to confirm the safety of
      the procedure.

PMID- 22583335
TI  - Efficacy and safety of the interleukin-1 antagonist rilonacept in Schnitzler
      syndrome: an open-label study.
AB  - BACKGROUND: Schnitzler syndrome (SchS) is a rare disease with suspected
      autoinflammatory background that shares several clinical symptoms, including
      urticarial rash, fever episodes, arthralgia, and bone and muscle pain with
      cryopyrin-associated periodic syndromes (CAPS). Cryopyrin-associated periodic
      syndromes respond to treatment with interleukin-1 antagonists, and single case
      reports of Schnitzler syndrome have shown improvement following treatment with
      the interleukin-1 blocker anakinra. This study evaluated the effects of the
      interleukin-1 antagonist rilonacept on the clinical signs and symptoms of SchS.
      METHODS: Eight patients with SchS were included in this prospective, single
      center, open-label study. After a 3-week baseline, patients received a
      subcutaneous loading dose of rilonacept 320 mg followed by weekly subcutaneous
      doses of 160 mg for up to 1 year. Efficacy was determined by patient-based daily
      health assessment forms, physician's global assessment (PGA), and measurement of
      inflammatory markers including C-reactive protein (CRP), serum amyloid A (SAA),
      and S100 calcium-binding protein A12 (S100A12). RESULTS: Treatment with
      rilonacept resulted in a rapid clinical response as demonstrated by significant
      reductions in daily health assessment scores and PGA scores compared with
      baseline levels (P < 0.05). These effects, which were accompanied by reductions
      in CRP and SAA, continued over the treatment duration. Rilonacept treatment was
      well tolerated. There were no treatment-related severe adverse events and no
      clinically significant changes in laboratory safety parameters. CONCLUSION:
      Rilonacept was effective and well tolerated in patients with SchS and may
      represent a promising potential therapeutic option.

PMID- 22583336
TI  - Coordination versus coupling of dicyanamide in molybdenum and manganese pyrazole
      complexes.
AB  - The reactions of cis-[MoCl(eta(3)-methallyl)(CO)(2)(NCMe)(2)] (methallyl =
      CH(2)C(CH(3))CH(2)) with Na(NCNCN) and pz*H (pzH, pyrazole, or dmpzH, 3,5
      dimethylpyrazole) lead to cis-[Mo(eta(3)-methallyl)(CO)(2)(pz*H)(MU-NCNCN
      kappa(2)N,N)](2) (pzH, 1a; dmpzH, 1b), where dicyanamide is coordinated as
      bridging ligand. Similar reactions with fac-[MnBr(CO)(3)(NCMe)(2)] lead to the
      pyrazolylamidino complexes fac-[Mn(pz*H)(CO)(3)(NH?C(pz*)NCN-kappa(2)N,N)] (pzH,
      2a; dmpzH, 2b), resulting from the coupling of pyrazol with one of the CN bonds
      of dicyanamide. The second CN bond of dicyanamide in 2a undergoes a second
      coupling with pyrazole after addition of 1 equiv of fac-[MnBr(CO)(3)(pzH)(2)],
      yielding the dinuclear doubly coupled complex [{fac-Mn(pzH)(CO)(3)}(2)(MU
      NH?C(pz)NC(pz)=NH-kappa(4)N,N,N,N)]Br (3). The crystal structure of 3 reveals the
      presence of two isomers, cis or trans, depending on whether the terminal
      pyrazoles are coordinated at the same or at different sides of the approximate
      plane defined by the bridging bis-amidine ligand. Only the cis isomer is detected
      in the crystal structure of the perchlorate salt of the same bimetallic cation
      (4), obtained by metathesis with AgClO(4). All the N-bound hydrogen atoms of the
      cations in 3 or 4 are involved in hydrogen bonds. Some of the C-N bonds of the
      pyrazolylamidino ligand have a character intermediate between single and double,
      and theoretical studies were carried out on 2a and 3 to confirm its electronic
      origin and discard packing effects. Calculations also show the essential role of
      bromide in the planarity of the tetradentate ligand in the bimetallic complex 3.

PMID- 22583337
TI  - No metabolic impact of surgical normalization of hyperandrogenism in
      postmenopausal women with ovarian androgen-secreting tumours.
AB  - AIM: To examine the impact of surgical normalization of testosterone on body
      weight and on glucose and lipid metabolism and insulin sensitivity in a group of
      hyperandrogenic women with ovarian androgen-secreting tumours (OAST). METHODS:
      Five consecutive postmenopausal hyperandrogenic patients (aged 63 +/- 5 years)
      with a diagnosis of OAST were prospectively evaluated. Clinical signs, symptoms
      and metabolic and hormonal parameters were collected at the time of the diagnosis
      and at follow-up, 12 months after surgical oophorectomy. A group of 15 age
      matched and body mass index-matched postmenopausal control women served as a
      reference group. RESULTS: At baseline, patients with OAST had very high
      testosterone levels and inappropriately low gonadotrophin levels for their
      menopausal status. All the women were overweight or obese, and one had a history
      of polycystic ovary syndrome and Type 2 diabetes. Twelve months after surgical
      oophorectomy, testosterone and gonadotrophin levels returned to appropriate
      values for menopausal status in all patients; however, no change in body weight
      was found. Fasting glucose levels slightly increased (P < 0.05) without any
      significant change in other metabolic parameters. In the woman with diabetes, a
      moderate decrease in haemoglobin A1c occurred. Red blood cell count and
      haematocrit values were normalized (P < 0.05, respectively). CONCLUSION:
      Normalization of androgen levels achieved after surgical oophorectomy did not
      cause any significant change in body weight and insulin sensitivity. These
      findings may offer a different perspective on the impact of hyperandrogenaemia on
      metabolism.

PMID- 22583338
TI  - Interleukin-2 receptor antagonist does not decrease biopsy-proven acute rejection
      among adult Chinese kidney transplant recipients.
AB  - Induction therapy with interleukin-2 receptor antagonist (IL2RA) is widely used
      for renal transplant recipients and this study aimed to examine the impact of
      IL2RA among Chinese renal transplant recipients. Two hundred and thirty-eight
      Chinese renal transplant recipients aged 18-65 years at the Taichung Veterans
      General Hospital from January 2004 to July 2009 were retrospectively studied to
      assess the influence of IL2RA on biopsy-proven acute rejection (BPAR) within 1
      year. Secondary outcomes included acute rejection rate in the first 3 months,
      delayed graft function, post-transplant diabetes mellitus, and malignancy. Cox
      proportional hazard analysis was used for multivariate analysis. Of all the
      patients, 116 received IL2RA (basiliximab, n = 44; daclizumab, n = 72) and 122
      had no induction therapy. The mean follow-up duration was 43.3 months (range, 1
      79 months). Overall, 227 (95.4%) patients completed the 12-month follow-up period
      with a functioning graft. No difference of BPAR was observed between the two
      groups and the secondary outcomes were also similar. After adjusting potential
      covariates with Cox regression, IL2RA use still provided no benefit on BPAR. In
      conclusion, there is no benefit of IL2RA in decreasing BPAR was observed in our
      study. Routine use of IL2RA for adult Chinese kidney transplant recipients may
      not be as effective as we thought before. More research is still needed to
      elucidate the effect of IL2RA among Chinese kidney transplant recipients.

PMID- 22583339
TI  - Advances in the treatment of melasma: a review of the recent literature.
AB  - BACKGROUND: Melasma is an acquired pigmentary disorder classically manifesting as
      symmetric hyperpigmented macules and patches on the face. It most commonly
      affects women of reproductive age with darker skin tones but may also affect
      adolescents, older women, and men. Although its pathogenesis remains unclear,
      known risk factors include ultraviolet radiation, hormonal variations of
      pregnancy, thyroid disease, oral contraceptives, and antiseizure medications.
      Hydroquinone-containing topical agents are the current standard for melasma
      treatment, but concern about side effects and long-term safety has spurred
      efforts to develop alternative treatment options. OBJECTIVES: To review recent
      advances in melasma treatment. MATERIALS AND METHODS: MEDLINE was searched from
      2006 to the present for randomized controlled trials (RCTs) of melasma
      treatments. RESULTS: Nineteen published RCTs were found covering interventions
      such as topical therapies, chemical peels, and electromagnetic devices. The
      outcomes of the studies were summarized into tabular form for easy reference and
      comparison. CONCLUSIONS: Although melasma is difficult to treat, novel
      therapeutic modalities have emerged. Further RCT need to be performed to better
      assess the safety and efficacy of these novel treatment modalities, especially
      for the long-term maintenance of melasma.

PMID- 22583340
TI  - The critical role of nurturing environments for promoting human well-being.
AB  - The recent Institute of Medicine report on prevention (National Research Council
      & Institute of Medicine, 2009) noted the substantial interrelationship among
      mental, emotional, and behavioral disorders and pointed out that, to a great
      extent, these problems stem from a set of common conditions. However, despite the
      evidence, current research and practice continue to deal with the prevention of
      mental, emotional, and behavioral disorders as if they are unrelated and each
      stems from different conditions. This article proposes a framework that could
      accelerate progress in preventing these problems. Environments that foster
      successful development and prevent the development of psychological and
      behavioral problems are usefully characterized as nurturing environments. First,
      these environments minimize biologically and psychologically toxic events.
      Second, they teach, promote, and richly reinforce prosocial behavior, including
      self-regulatory behaviors and all of the skills needed to become productive adult
      members of society. Third, they monitor and limit opportunities for problem
      behavior. Fourth, they foster psychological flexibility-the ability to be mindful
      of one's thoughts and feelings and to act in the service of one's values even
      when one's thoughts and feelings discourage taking valued action. We review
      evidence to support this synthesis and describe the kind of public health
      movement that could increase the prevalence of nurturing environments and thereby
      contribute to the prevention of most mental, emotional, and behavioral disorders.
      This article is one of three in a special section (see also Munoz Beardslee, &
      Leykin, 2012; Yoshikawa, Aber, & Beardslee, 2012) representing an elaboration on
      a theme for prevention science developed by the 2009 report of the National
      Research Council and Institute of Medicine.

PMID- 22583341
TI  - The effects of poverty on the mental, emotional, and behavioral health of
      children and youth: implications for prevention.
AB  - This article considers the implications for prevention science of recent advances
      in research on family poverty and children's mental, emotional, and behavioral
      health. First, we describe definitions of poverty and the conceptual and
      empirical challenges to estimating the causal effects of poverty on children's
      mental, emotional, and behavioral health. Second, we offer a conceptual framework
      that incorporates selection processes that affect who becomes poor as well as
      mechanisms through which poverty appears to influence child and youth mental
      health. Third, we use this conceptual framework to selectively review the growing
      literatures on the mechanisms through which family poverty influences the mental,
      emotional, and behavioral health of children. We illustrate how a better
      understanding of the mechanisms of effect by which poverty impacts children's
      mental, emotional, and behavioral health is valuable in designing effective
      preventive interventions for those in poverty. Fourth, we describe strategies to
      directly reduce poverty and the implications of these strategies for prevention.
      This article is one of three in a special section (see also Biglan, Flay, Embry,
      & Sandler, 2012; Munoz, Beardslee, & Leykin, 2012) representing an elaboration on
      a theme for prevention science developed by the 2009 report of the National
      Research Council and Institute of Medicine.

PMID- 22583348
TI  - Ethical? Toward whom?
AB  - Comments on the original article, "Nonrational processes in ethical decision
      making" by M. D. Rogerson et al (see record 2011-19198-001). Among the many
      insightful points made by Rogerson, Gottlieb, Handelsman, Knapp, and Younggren
      (October 2011) regarding nonrational processes in ethical decision making, one
      deserves further explication: Many of psychologists' ethical decisions lead to
      actions done to someone. Unfortunately, frameworks and models of ethical decision
      making frequently neglect this fact by implying that the decisions happen in the
      abstract, but in truth, these decisions often affect a specific recipient.
      Importantly, the characteristics of that specific recipient, especially as
      perceived by the psychologist, can have a powerful impact on the process of
      ethical decision making (Caughron et al., 2011). It would be wise to add such a
      hypothetical to the list of specific questions that Rogerson et al recommended
      psychologists ask themselves: Would I make the same ethical decision if the
      person(s) toward whom the decision is directed had different characteristics?

PMID- 22583342
TI  - Major depression can be prevented.
AB  - The 2009 Institute of Medicine report on prevention of mental, emotional, and
      behavioral disorders (National Research Council & Institute of Medicine, 2009b)
      presented evidence that major depression can be prevented. In this article, we
      highlight the implications of the report for public policy and research.
      Randomized controlled trials have shown that the incidence of major depressive
      episodes can be significantly reduced. Meta-analyses suggest that 22% to 38% of
      major depressive episodes could be prevented with currently available methods. We
      argue that if major depressive episodes can be prevented, the health care system
      should provide routine access to evidence-based depression prevention
      interventions, just as it provides inoculations for other common and debilitating
      health problems. At the same time, researchers should pursue the major directions
      advocated by the Institute of Medicine report to increase the enduring
      effectiveness of future prevention interventions. These directions include taking
      a developmental perspective, learning to identify groups at high risk, and
      testing evidence-based interventions that are likely to have the widest reach.
      Scientific evidence has shown that clinical depression can be averted. Our
      societies must take action to reduce clinical depression to the lowest possible
      level. This article is one of three in a special section (see also Biglan, Flay,
      Embry, & Sandler, 2012; Yoshikawa, Aber, & Beardslee, 2012) representing an
      elaboration on a theme for prevention science developed by the 2009 report of the
      National Research Council and Institute of Medicine.

PMID- 22583349
TI  - A plea for virtue in ethics.
AB  - Comments on the original article, "Nonrational processes in ethical decision
      making" by M. D. Rogerson et al (see record 2011-19198-001). The current authors
      suggest that Rogerson, Gottlieb, Handelsman, Knapp, and Younggren (October 2011)
      presumed that the only ethical theories available for grounding decision-making
      models are of the rational, neoliberal variety. Rogerson et al stated,
      "Contextual, interpersonal, and intuitive factors are inextricably linked and
      inexorably influential in the process of ethical decision making. Ethical theory
      would benefit from encompassing these subtle yet powerful forces" (Rogerson et
      al., 2011, p. 616). They sought to augment these models with a cluster of
      contextual considerations, appending to them accounts of emotion, context, and
      intuition. First, notwithstanding the theories attributed to (the caricature of)
      Kant and his ilk, there are several ethical theories that include an account of
      what Rogerson et al. (2011) consider to be "nonrational" processes. From feminist
      theories to narrative ethics, sophisticated contextual theories have been
      developed and are readily available. Second, we question whether thick contextual
      considerations can simply be tacked on to extant models of decision making
      originally built upon a philosophical foundation that assumes a rational,
      autonomous agent who deliberates independently and logically.

PMID- 22583351
TI  - Percutaneous cryoablation of solitary sporadic renal cell carcinomas.

PMID- 22583353
TI  - Synthesis and catalysis of location-specific cobalt nanoparticles supported by
      multiwall carbon nanotubes for Fischer-Tropsch synthesis.
AB  - Cobalt nanoparticles located on the concave internal surface of multiwalled
      carbon nanotubes (Co-in-MW-CNTs) and the convex external surface of MW-CNTs (Co
      on-MW-CNTs) were synthesized. Their catalytic performances in Fischer-Tropsch
      synthesis (FTS) were investigated. A correlation between the location,
      pretreatment, and surface chemistry of the cobalt nanoparticles and the catalytic
      selectivity in FTS was built. It is found that the selectivity in production of
      C(5+) molecules through FTS on cobalt catalysts supported by MW-CNTs depends on
      activation temperatures and surface chemistry of the cobalt nanoparticles. A
      pretreatment at 300  degrees C in H(2) flow results in a different surface
      chemistry for Co-in-MW-CNTs than for Co-on-MW-CNTs, which leads to a difference
      in selectvity to the production of C(5+) molecules. Pretreatment at a relatively
      high temperature, 400  degrees C, in H(2) flow produces completely reduced Co
      nanoparticles in Co-in-MW-CNTs and Co-on-MW-CNTs. There is no signifcant
      difference in catalytic selectivity between the two catalysts upon pretreatment
      at 400  degrees C. The absence of a significant difference in catalytic
      selectivity of metallic Co-on-MW-CNTs and metallic Co-in-MW-CNTs suggests that
      the electronic effect of the MW-CNT support does not significantly affect the
      C(5+) selectivity of cobalt catalysts in FTS.

PMID- 22583352
TI  - Comparison of pulmonary function and respiratory symptoms in water pipe and
      cigarette smokers.
AB  - BACKGROUND AND OBJECTIVE: A major type of smoking in Middle Eastern countries is
      water pipe (WP) smoking. In the present study, pulmonary function tests (PFT) and
      respiratory symptoms (RS) were compared in WP smokers and deep inspiration (S-DI)
      or normal inspiration (S-NI) cigarette smokers. METHODS: Pulmonary function and
      RS were compared among WP smokers, deep or normal inspiration cigarette smokers,
      and non-smokers. RESULTS: All PFT values in WP smokers and S-DI, but only some
      values in S-NI, were lower than those of non-smokers (P < 0.05 to P < 0.001). In
      addition, all PFT values in WP smokers and S-DI were lower than the corresponding
      values in S-NI, except for forced expiratory volume in 1 s and maximal expiratory
      flow at 25% of forced vital capacity (P < 0.05 to P < 0.001). The prevalence of
      RS, except for sputum production, was greater in all three groups of smokers than
      in non-smokers (P < 0.05 to P < 0.001). However, the severity of most RS in WP
      smokers and S-DI, but only the severity of wheezing in S-NI, was greater than
      that in non-smokers (P < 0.05 to P < 0.01). There were inverse correlations for
      PFT values and positive correlations for RS, with duration and total amount of
      smoking (P < 0.05 to P < 0.001). CONCLUSIONS: The results from this study showed
      that there was a profound effect of WP smoking on PFT values and RS, which were
      similar to the effects of deep inspiration cigarette smoking.

PMID- 22583354
TI  - Prostaglandin endoperoxide synthase 2 (PTGS2) and prostaglandins F2alpha and E2
      synthases (PGFS and PGES) expression and prostaglandin F2alpha and E2 secretion
      following oestrogen and/or progesterone stimulation of the feline endometrium.
AB  - Sex steroids in synergy with prostaglandins (PG) are involved in the regulation
      of cyclic ovarian function. In this study, we investigated the mRNA expression of
      three genes involved in arachidonic acid (AA) metabolism and hence PG production
      in domestic cats: PG-endoperoxide synthase (PTGS2), PGF(2alpha) synthase (PGFS)
      and PGE(2) synthase (PGES). Feline endometria (n = 16) were collected at oestrus
      and mid and late phases of pseudopregnancy. In addition, the effects of E(2)
      and/or P(4) on PG secretion and gene expression on endometrial explants were
      studied in an in vitro culture system. Expression levels of all examined genes
      were up-regulated at the mid phase of pseudopregnancy. The effects of E(2) and/or
      P(4) treatment on both PG secretion and expression of the genes were observed
      after 12 h of culture. Expression of PGES was significantly up-regulated by E(2)
      plus P(4) at oestrus and the mid phase of pseudopregnancy and was also up
      regulated by a single treatment with P(4) at late pseudopregnancy (p < 0.05).
      Simultaneous incubation with E(2) and P(4) up-regulated PTGS2 gene expression at
      oestrus and mid-luteal phase (p < 0.05). Progesterone plus E(2) significantly
      increased PGE(2) secretion at oestrus and the mid phase of pseudopregnancy.
      However, treatment with E(2) and/or P(4) affected neither PGF(2alpha) secretion
      nor PGFS expression at any phase after 12 h of culture. The overall findings
      indicate that genes involved in PG synthesis are up-regulated at the mid phase of
      pseudopregnancy. An increase in PGE(2) secretion and up-regulation of PGES and
      PTGS2 are the main responses of the endometrium to treatment with E(2) and P(4)
      at oestrus and the mid phase of pseudopregnancy in the cat. These data support
      the hypothesis that ovarian sex steroids via endometrial PGE(2) are involved in
      endocrine homoeostasis, especially at oestrus and the mid, but not the late,
      phase of pseudopregnancy in cats.

PMID- 22583355
TI  - A clinical-pathological review of hidradenitis suppurativa: using
      immunohistochemistry one disease becomes two.
AB  - We report the results of a re-examination of a series of 57 biopsies from 50
      patients with the clinical diagnosis of hidradenitis suppurativa, submitted to
      the Department of Pathology at the University Hospital of Northern Norway,
      Tromso, Norway. The biopsy material came from hospitals and physicians all over
      northern Norway in the years 2000-2007. All tissue material was resectioned and
      stained with the immunohistochemical reagent, cytokeratin (AE1/AE3/PKC26), and
      that made it possible to divide the material into two different disease
      categories: (1) 36 biopsies from 30 cases had tissue inflammation after rupture
      of keratin-rich epidermal cysts, which we call 'horny cell inflammation',
      followed by extensive cutaneous thrombi and infarcts, and (2) 21 biopsies from 20
      cases had 'apocrinitis' defined here as an inflammatory destruction of apocrine
      skin glands, and partly of close eccrine glands. The two disease populations
      differed: the patients with a diagnosis of horny cell inflammation were younger
      and mainly women; those with a diagnosis of apocrinitis, as defined here, were
      older, men and women equally represented.

PMID- 22583356
TI  - Down-regulation of Notch receptor signaling pathway induces caspase-dependent and
      caspase-independent apoptosis in lung squamous cell carcinoma cells.
AB  - Notch receptor signaling pathway (NRSP) is increasingly linked to carcinogenesis.
      Non-small cell lung cancer (NSCLC) appears to actively utilize this conserved
      developmental pathway. The aims of this study are to determine whether or not
      Notch 1-4 are overexpressed in NSCLC tissues compared with normal lung tissues
      and whether inhibiting NRSP could induce caspase-dependent or caspase-independent
      apoptosis. Immunohistochemistry was used to evaluate the expression of Notch 1-4
      in 101 NSCLC tissue samples and 30 normal lung tissue samples. DAPT was used to
      repress NRSP in SK-MES-1 cells. Apoptosis was determined by Annexin V and PI
      staining. Cleaved poly ADP-ribose polymerase (PARP) was measured by Western blot;
      X-linked inhibitor of apoptosis protein (XIAP) and Survivin were assessed by qRT
      PCR and Western blot; the release of second mitochondria-derived activator of
      caspase (Smac) from mitochondria to cytoplasm was evaluated by Western blot; the
      subcellular locations of endonuclease G (Endo G) and apoptosis inducing factor
      (AIF) were observed by Western blot and indirect immunofluorescence analysis.
      (Mech Dev, 98, 2000, 95) Notch 1-4 are up-regulated in NSCLC tissues and Notch 1,
      2 are positively correlated with lymph node metastasis, (Proc Natl Acad Sci U S
      A, 106, 2009, 22293) DAPT treatment could inhibit NRSP and induce apoptosis, with
      a marked increase in cleaved PARP, decreases in XIAP and Survivin proteins and
      concomitant release of Smac, EndoG, and AIF from mitochondria, indicating that
      inhibiting NRSP by DAPT triggers caspase-dependent and caspase-independent
      apoptosis.

PMID- 22583357
TI  - Oestrogen receptor beta in NSCLC - prevalence, proliferative influence,
      prognostic impact and smoking.
AB  - In non-small-cell lung carcinoma (NSCLC) there are gender differences. The female
      gender is associated with more adenocarcinomas (ADCA), among both smokers and non
      smokers compared to men. Women with NSCLC have a better prognosis compared to
      men, regardless of other factors. A possible role for oestrogen receptor (ER)
      signalling has been proposed. The role for ERbeta in NSCLC is still not clear,
      especially concerning the impact of smoking. In a material of NSCLC (n = 262),
      ERbeta and cyclins A1 and A2 were studied by immunohistochemistry on formalin
      fixed paraffin embedded tissue. In 137 of those cases, frozen material was
      available, on which expression analysis of ESR2 (ERbeta) and cyclin A1 were
      performed. Data were correlated to histology, gender, smoking habits, stage and
      clinical outcome. ERbeta was expressed in 86% of the cases. ERbeta was most
      frequently expressed in Stage I ADCAs, especially in male subjects. A correlation
      between ERbeta expression and cyclins was observed in ADCA, also with a male
      predominance. ERbeta transcripts had a positive prognostic impact in ADCA. ERbeta
      transcripts were increased in NSCLC among smokers compared to non-smokers. In
      conclusion, our data support a role for ERbeta in lung ADCAs, proposing a role
      for ERbeta in lungcarcinogenesis, especially among smokers.

PMID- 22583358
TI  - K-ras mutations are correlated to lymph node metastasis and tumor stage, but not
      to the growth pattern of colon carcinoma.
AB  - In colorectal carcinoma, pathological assessment of tumors is essential for
      determining therapy and prognosis of the disease. Molecular associations of tumor
      complexity index and genetic alternations can be helpful to understand the tumor
      progression mechanism. Oncogenic K-ras is one of the major colorectal cancer
      associated genes, and is mutated in up to 50% of colorectal cancers. In this
      current study, we correlated tumor complexity index with mutations in K-ras codon
      12, 13, and 61 in association with different clinicopathological parameters such
      as TNM stage, localization, sex, and age. Formalin-fixed paraffin embedded tissue
      blocks from colon cancer samples was selected from 88 patients diagnosed with
      adenocarcinoma. Mutations in the K-ras gene were detected using pyrosequencing
      technique. Tumor complexity index was calculated using immunohistochemically
      stained images of the tumor outline of the specimens and then analyzing these
      pictures using Photoshop CS, Fovea Pro, and Image J computer programs.
      Statistical analysis was performed with SPSS. K-ras mutations were detected in 17
      (19.3%) colon cancer samples. Most of the samples were at a lower complexity
      index. No correlation was observed between K-ras mutations and complexity index.
      However, K-ras mutations were correlated with regional lymph node metastasis and
      tumor stages and complexity index with tumor wall penetration. In conclusion,
      complexity index and K-ras mutations are independent events; however, both
      correlate with tumor progression and are important in the biologic development of
      colon carcinoma.

PMID- 22583359
TI  - Knockdown of BDNF suppressed invasion of HepG2 and HCCLM3 cells, a mechanism
      associated with inactivation of RhoA or Rac1 and actin skeleton disorganization.
AB  - Brain-derived neurotrophic factor (BDNF) and its primary receptor tropomysin
      related kinase B (TrkB) mediate critical signalings for supporting survival and
      growth of neurons. Even though we have previously confirmed that more expressions
      of BDNF and TrkB were closely correlated with multiple and advanced
      hepatocellular carcinoma (HCC), the exact mechanisms underlying have not been
      investigated. The expressions of BDNF and TrkB were examined by western blot and
      BDNF secretion was evaluated by ELISA in human HCC cell lines of HepG2 and HCCLM3
      with high metastatic potential. BDNF knockdown was performed by specific BDNF
      siRNA transfection in HCC cells, actin cytoskeleton was shown by FITC-phalloidin
      staining and the activations of RhoA, Rac1 or Cdc42 were determined using western
      blot. Cell apoptosis and invasion were examined by flow cytometry and transwell
      assay, respectively. More expressions of BDNF and TrkB were found in HCCLM3 than
      in HepG2 cells. Inhibited expression of BDNF by specific siRNA showed impaired
      actin polymerization and decreased activations of RhoA or Rac1 in both HepG2 and
      HCCLM3 cells. BDNF knockdown also induced apoptosis and suppressed invasion of
      both HepG2 and HCCLM3 cells. Our results suggested a role of BDNF/TrkB in
      confering HCCLM3 cells advantage of metastasis, and BDNF knockdown inhibited cell
      invasion probably through the blocked actin polymerization and the correlated
      inactivation of RhoA or Rac1. Aiming at BDNF/TrkB signaling interruption may be
      an effective strategy to prevent HCC progression.

PMID- 22583360
TI  - Genital seborrheic keratoses are human papillomavirus-related lesions. A linear
      array genotyping test study.
AB  - Controversy exists about the meaning of human papillomavirus (HPV) detection in
      seborrheic keratosis (SK). To clarify the pathogenic contributing role of HPV in
      the development of genital SK, we have studied 40 genital SKs, 20 extragenital
      SKs, and 20 non-SK genital lesions by polymerase chain reaction for HPV, using a
      Linear Array Genotyping test that detects 37 genital HPV types. Twenty-eight of
      the 40 genital SK specimens (70%) were positive for HPV. Twenty-seven of the 28
      positive cases (96%) contained HPV6, one of them associated to HPV18 and HPV35
      (4%), and the remaining lesion (4%) harbored HPV55. However, HPV was detected in
      only 2/20 extragenital SK samples (10%) and in 1/20 non-SK genital lesions (5%).
      Our results support a pathogenic relationship between HPV and genital SK by
      showing: 1) a high rate of virus detection in these lesions, with a strong
      predilection for HPV6, and 2) scarcity of genital HPV types in most of the
      remaining non-SK cutaneous genital lesions and in the extragenital SKs. HPV
      cannot be found in a minority of genital SKs using highly sensitive techniques,
      and therefore, other presently unknown factors may also be implied in the
      pathogenesis of these lesions.

PMID- 22583361
TI  - Smooth muscle in the human mitral valve: extent and implications for dynamic
      modelling.
AB  - The mitral valve is increasingly been regarded as having dynamic and contractile
      capabilities, but the presence of muscle in the valve has been investigated to a
      limited extent. The aim of this study was to investigate the presence,
      architecture and phenotype of muscle in the human mitral valve. Twelve mitral
      valves were cut into strips, sectioned for histology, and the cut edges examined
      by microscope after staining included immunophenotyping. Smooth muscle bundles
      were present at the atrial side of the leaflets, and distinctly more in the
      anterior leaflet than in the posterior leaflet. The smooth muscle bundles
      extended up to two-thirds the distance from the annulus to the rim of the
      leaflets, and they ran in various directions, but seemingly mainly perpendicular
      to the annulus. The thickness and density of the bundles seemed to decrease with
      the distance from the annulus, and also in a radial direction from the centre
      portion of each leaflets attachment at the annulus towards the rim. Cross
      striation was not detected. Cardiac muscle in the left atrial wall extended into
      the annular base of the leaflets in close proximity to the annular border of the
      smooth muscle bundles in the leaflets. In conclusion, especially the anterior
      leaflet of the mitral valve seems to have a separate smooth muscle formed as a
      meshwork of bundles close to the atrial surface.

PMID- 22583362
TI  - Aminoglycoside resistance in clinical Escherichia coli and Klebsiella pneumoniae
      isolates from Western Norway.
AB  - Resistance to gentamicin in Escherichia coli from blood culture has shown an
      increase over the past decade in Norway. This study was done to investigate
      aminoglycoside resistance in Escherichia coli and Klebsiella pneumoniae in
      Western Norway. The material included 49 blood culture isolates which had shown
      aminoglycoside resistance collected during 2000-2009. To investigate co
      resistance to alternative antibiotics and dynamics involved in aminoglycoside
      resistance 67 isolates (mostly from urine) exhibiting resistance to both
      aminoglycosides and extended spectrum beta-lactam antibiotics were also included.
      MIC values were obtained for amikacin, gentamicin, kanamycin, netilmicin,
      streptomycin and tobramycin and all isolates were screened using PCR for aac(3)
      II and aac(6')-Ib, encoding aminoglycoside modifying enzymes. Resistance to >=3
      aminoglycosides was found in 92% of the isolates and 60.3% showed resistance to
      gentamicin, netilmicin, tobramycin and kanamycin. Amikacin resistance was low. Co
      resistance to ciprofloxacin was found in 88% of the isolates with gentamicin
      resistance. aac(3)-IIa/c was found in 79.3% and aac(6')-Ib in 37.9% of the
      isolates and 28.4% harboured both genes. aac(6')-Ib-cr, possibly contributing to
      ciprofloxacin resistance was found mostly in extended spectrum beta-lactamase
      producers. The aminoglycoside resistance patterns indicate co-existence of
      multiple resistance mechanisms. The use of ciprofloxacin and third generation
      cephalosporins is likely to have contributed to the increase in aminoglycoside
      resistance in Norway.

PMID- 22583363
TI  - Primary drug resistance to anti-tuberculosis drugs in major towns of Amhara
      region, Ethiopia.
AB  - Drug resistance is a major obstacle to effective TB control program performance.
      In this study, we assessed the prevalence of primary drug resistance in
      Mycobacterium tuberculosis (Mtb) isolates in Amhara Region, Ethiopia. A total of
      112 Mtb isolates from cases with newly diagnosed pulmonary TB were subjected to
      drug susceptibility testing (DST) in a cross-sectional study. Isolates were
      tested for sensitivity to isoniazid, rifampicin, ethambutol, and streptomycin
      using the MGIT 960 protocol. A total of 93 Mtb isolates yielded valid DST results
      and 28 (30.1%) were resistant to one or more of first line anti-TB drugs. One
      isolate (1.0%) was multi-drug resistant (MDR), five (5.4%) were classified as
      poly-resistant and 22 showed single drug resistance to either streptomycin (n =
      19) or isoniazid (n = 3). Isolates from HIV-positive patients were more likely to
      be resistant to at least one of the four anti-TB drugs compared with HIV-negative
      individuals (odds ratio 2.76, 95% confidence interval 1.06-7.22; p = 0.03). The
      study showed a high prevalence of primary drug resistance. Even though the
      prevalence of MDR was low, conditions that can contribute to the development of
      MDR are increasing. Therefore, regular monitoring of drug resistance and enhanced
      implementation of TB/HIV collaborative activities in the study region are
      imperative.

PMID- 22583364
TI  - Immunohistochemical verification of ductal differentiation in prostate cancer.
AB  - Recent studies have shown that patients with prostate carcinomas exhibiting
      ductal differentiation have an unfavourable prognosis compared with those with
      purely acinar adenocarcinomas. We studied the expression of nine
      immunohistochemical markers to evaluate their value in delineating carcinomas
      with and without ductal differentiation. Thirteen tumours showing cellular
      characteristics and growth patterns typical of ductal differentiation were
      identified among 110 analysed prostatectomy specimens. The levels of cytoplasmic
      expression of chromogranine A (69% vs 19%, p = 0.0003) and nuclear expression of
      p53 (76% vs 12%, p < 0.0001) as well as nuclear expression of Ki-67 (69% vs 26%,
      p = 0.0047) in the tumour cells, were found to be statistically significantly
      different in the two tumour categories. Assessment of chromogranine A, p53 and Ki
      67 in prostate carcinoma may serve as useful adjunctive diagnostic tools for
      delineating more aggressive prostate cancer cases exhibiting ductal
      differentiation.

PMID- 22583365
TI  - Expressional and mutational analysis of ATRX gene in gastric, colorectal and
      prostate cancers.

PMID- 22583366
TI  - Comparison of bacterial communities in faeces of beef cattle fed diets containing
      corn and wet distillers' grain with solubles.
AB  - AIM: The mammalian intestinal microflora has been shown to impact host
      physiology. In cattle, intestinal bacteria are also associated with faecal
      contamination of environmental sources and human illness via foodborne pathogens.
      Use of wet distillers' grains with solubles (WDGS) in cattle feed creates a
      gastrointestinal environment where some bacterial species are enriched. Here, we
      examine if a diet containing 40% WDGS results in fundamentally different
      microbial community structures. METHODS AND RESULTS: The 20,002 16S r-RNA gene
      sequences from 20 beef cattle were analysed using Sanger sequencing methods. At
      the genus level, Prevotella (Gram negative) and Anaerobacter (Gram positive) were
      the most frequently occurring bacteria in our beef cattle faecal samples. Diet
      associated differences in prevalence were noted for Prevotella but not
      Anaerobacter. CONCLUSIONS: Diet affects community structure. Faecal communities
      of co-housed beef cattle are not identical. SIGNIFICANCE AND IMPACT OF THE STUDY:
      It is known that a diet of 40% corn-based WDGS increases the generic Escherichia
      coli in the faeces and enriches E. coli O157:H7. The results from the current
      study suggest that in addition to previously observed changes in E. coli, the
      entire bacterial community structure is different for animals fed 40% corn-based
      WDGS compared to a traditional corn-finishing diet.

PMID- 22583367
TI  - When biostatistics is a neo-inductionist barrier to science.

PMID- 22583369
TI  - Are peripapillary intrascleral hemorrhages pathognomonic for abusive head trauma?
AB  - The American Academy of Pediatrics' Committee on Child Abuse and Neglect, Section
      on Ophthalmology, acknowledges that searching for retinal hemorrhages (RHs) in
      infants only in cases of suspected of abuse creates selection bias. However, they
      also recommend that postmortem eye removal might not be indicated "in children
      who have clearly died from witnessed severe accidental head trauma or otherwise
      readily diagnosed systemic medical conditions." Although infrequently described
      in the child abuse literature, peripapillary intrascleral hemorrhages (bleeding
      in the sclera at the optic nerve insertion)--putatively from severe repetitive
      acceleration/deceleration forces with or without blunt head trauma--have been
      considered essentially pathognomonic for abusive head trauma (shaken baby
      syndrome). We present two neonates who sustained accidental, severe in utero head
      injuries and had associated extensive RHs and optic nerve sheath hemorrhages with
      peripapillary intrascleral hemorrhages detected at autopsy. Neither neonate had a
      documented clinical fundal examination in the intensive care unit.

PMID- 22583371
TI  - A new index for acute rejection after renal transplant: Notch receptor-1.
AB  - OBJECTIVES: This study aimed at investigating the relation between expression of
      Notch receptor-1 (Notch 1) in peripheral blood mononuclear cells and acute
      rejection after renal transplant. MATERIALS AND METHODS: Ninety-seven patients
      receiving a renal transplant were randomly selected. Peripheral blood samples
      before transplant and days 1, 3, 5, 7, 10, 14, 21, and 30 after transplant were
      retrospectively observed. Expression of Notch 1 was detected by flow cytometry
      and real-time quantitative polymerase chain reaction. RESULTS: Expression of
      Notch 1 was correlated with acute rejection and long-term renal function after
      transplant (as detected by the level of serum creatinine 6 months after
      transplant). Expression of Notch 1 in peripheral blood mononuclear cells
      increased before serum creatinine increased. Expression of Notch 1 can reveal the
      immune state of recipients after transplant, and Notch 1 expression at early time
      points after transplant can predict long-term renal function. CONCLUSIONS: Notch
      1 can serve as an important index for acute rejection and long-term renal
      function after transplant.

PMID- 22583370
TI  - Outside looking in: nanotube transistor intracellular sensors.
AB  - Nanowire-based field-effect transistors, including devices with planar and three
      dimensional configurations, are being actively explored as detectors for extra-
      and intracellular recording due to their small size and high sensitivities. Here
      we report the synthesis, fabrication, and characterization of a new needle-shaped
      nanoprobe based on an active silicon nanotube transistor, ANTT, that enables high
      resolution intracellular recording. In the ANTT probe, the source/drain contacts
      to the silicon nanotube are fabricated on one end, passivated from external
      solution, and then time-dependent changes in potential can be recorded from the
      opposite nanotube end via the solution filling the tube. Measurements of
      conductance versus water-gate potential in aqueous solution show that the ANTT
      probe is selectively gated by potential changes within the nanotube, thus
      demonstrating the basic operating principle of the ANTT device. Studies
      interfacing the ANTT probe with spontaneously beating cardiomyocytes yielded
      stable intracellular action potentials similar to those reported by other
      electrophysiological techniques. In addition, the straightforward fabrication of
      ANTT devices was exploited to prepare multiple ANTT structures at the end of
      single probes, which enabled multiplexed recording of intracellular action
      potentials from single cells and multiplexed arrays of single ANTT device probes.
      These studies open up unique opportunities for multisite recordings from
      individual cells through cellular networks.

PMID- 22583368
TI  - Monothiol CGFS glutaredoxins and BolA-like proteins: [2Fe-2S] binding partners in
      iron homeostasis.
AB  - Monothiol glutaredoxins (Grxs) with a signature CGFS active site and BolA-like
      proteins have recently emerged as novel players in iron homeostasis. Elegant
      genetic and biochemical studies examining the functional and physical
      interactions of CGFS Grxs in the fungi Saccharomyces cerevisiae and
      Schizosaccharomyces pombe have unveiled their essential roles in intracellular
      iron signaling, iron trafficking, and the maturation of Fe-S cluster proteins.
      Biophysical and biochemical analyses of the [2Fe-2S] bridging interaction between
      CGFS Grxs and a BolA-like protein in S. cerevisiae provided the first molecular
      level understanding of the iron regulation mechanism in this model eukaryote and
      established the ubiquitous CGFS Grxs and BolA-like proteins as novel Fe-S cluster
      binding regulatory partners. Parallel studies focused on Escherichia coli and
      human homologues for CGFS Grxs and BolA-like proteins have supported the studies
      in yeast and provided additional clues about their involvement in cellular iron
      metabolism. Herein, we review recent progress in uncovering the cellular and
      molecular mechanisms by which CGFS Grxs and BolA-like proteins help regulate iron
      metabolism in both eukaryotic and prokaryotic organisms.

PMID- 22583372
TI  - Exogenous administration of PACAP alleviates traumatic brain injury in rats
      through a mechanism involving the TLR4/MyD88/NF-kappaB pathway.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is effective in
      reducing axonal damage associated with traumatic brain injury (TBI), and has
      immunomodulatory properties. Toll-like receptor 4 (TLR4) is an important mediator
      of the innate immune response. It significantly contributes to neuroinflammation
      induced by brain injury. However, it remains unknown whether exogenous PACAP can
      modulate TBI through the TLR4/adapter protein myeloid differentiation factor 88
      (MyD88)/nuclear factor-kappaB (NF-kappaB) signaling pathway. In this study, we
      investigated the potential neuroprotective mechanisms of PACAP pretreatment in a
      weight-drop model of TBI. PACAP38 was microinjected intracerebroventricularly
      before TBI. Brain samples were extracted from the pericontusional area in the
      cortex and hippocampus. We found that TBI induced significant upregulation of
      TLR4, with peak expression occurring 24 h post-trauma, and that pretreatment with
      PACAP significantly improved motor and cognitive dysfunction, attenuated neuronal
      apoptosis, and decreased brain edema. Pretreatment with PACAP inhibited
      upregulation of TLR4 and its downstream signaling molecules MyD88, p-IkappaB, and
      NF-kappaB, and suppressed increases in the levels of the downstream inflammatory
      agents interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha),
      in the brain tissue around the injured cortex and in the hippocampus.
      Administration of PACAP both in vitro and in vivo attenuated the ability of the
      TLR4 agonist lipopolysaccharide (LPS) to increase TLR4 protein levels. Therefore,
      PACAP exerts a neuroprotective effect in this rat model of TBI, by inhibiting a
      secondary inflammatory response mediated by the TLR4/MyD88/NF-kappaB signaling
      pathway in microglia and neurons, thereby reducing neuronal death and improving
      the outcome following TBI.

PMID- 22583373
TI  - Topical application of PPARalpha (but not beta/delta or gamma) suppresses atopic
      dermatitis in NC/Nga mice.
AB  - BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) are nuclear
      receptors, which regulate not only adipogenesis and proliferation/differentiation
      but also the immune response of cells. Because topical application of the
      activators of some PPAR isoforms improved clinical symptoms in patients with
      atopic dermatitis (AD), we investigated the role of PPAR activators using a
      murine AD model in NC/Nga mice; to the best of our knowledge, this has not been
      previously reported. METHODS: Activators of three PPAR isoforms (alpha,
      beta/delta, gamma) were topically applied on inflamed skin in a murine AD model
      that was developed by repeated topical application of mite antigen in NC/Nga
      mice. The efficacy of each topical PPAR activator was evaluated immunologically
      and serologically. RESULTS: Topical application of the PPARalpha activator, but
      not of the activators of PPARbeta/delta or PPARgamma, improved clinical
      dermatitis, reduced inflammatory cell infiltration in the dermis, and alleviated
      the elevation of serum IgE levels. In addition, PPARalpha expression was
      downregulated in the epidermis in our murine AD model, as is seen in patients
      with AD. CONCLUSIONS: Topical application of PPARalpha activator could be a
      potent therapeutic agent for patients with AD and could take the place of topical
      steroid treatments.

PMID- 22583374
TI  - Chloride and organic osmolytes: a hybrid strategy to cope with elevated
      salinities by the moderately halophilic, chloride-dependent bacterium
      Halobacillus halophilus.
AB  - Salt acclimation in moderately halophilic bacteria is the result of action of a
      grand interplay orchestrated by signals perceived from the environment. To
      elucidate the cellular players involved in sensing and responding to changing
      salinities we have determined the genome sequence of Halobacillus halophilus, a
      Gram-positive moderate halophilic bacterium that has a strict requirement for the
      anion chloride. Halobacillus halophilus synthesizes a multitude of different
      compatible solutes and switches its osmolyte strategy with the external salinity
      and growth phase. Based on the emerging genome sequence, the compatible solutes
      glutamate, glutamine, proline and ectoine have already been experimentally
      studied. The biosynthetic routes for acetyl ornithine and acetyl lysine are also
      delineated from the genome sequence. Halobacillus halophilus is nutritionally
      very versatile and most compatible solutes cannot only be produced but also used
      as carbon and energy sources. The genome sequence unravelled isogenes for many
      pathways indicating a fine regulation of metabolism. Halobacillus halophilus is
      unique in integrating the concept of compatible solutes with the second
      fundamental principle to cope with salt stress, the accumulation of molar
      concentrations of salt (Cl(-)) in the cytoplasm. Extremely halophilic
      bacteria/archaea, which exclusively rely on the salt-in strategy, have a high
      percentage of acidic proteins compared with non-halophiles with a low percentage.
      Halobacillus halophilus has an intermediate position which is consistent with its
      ability to integrate both principles.

PMID- 22583375
TI  - Differential effects of simvastatin on IL-13-induced cytokine gene expression in
      primary mouse tracheal epithelial cells.
AB  - BACKGROUND: Asthma causes significant morbidity worldwide in adults and children
      alike, and incurs large healthcare costs. The statin drugs, which treat
      hyperlipidemia and cardiovascular diseases, have pleiotropic effects beyond
      lowering cholesterol, including immunomodulatory, anti-inflammatory, and anti
      fibrotic properties which may benefit lung health. Using an allergic mouse model
      of asthma, we previously demonstrated a benefit of statins in reducing
      peribronchiolar eosinophilic inflammation, airway hyperreactivity, goblet cell
      hyperplasia, and lung IL-4 and IL-13 production. OBJECTIVES: In this study, we
      evaluated whether simvastatin inhibits IL-13-induced pro-inflammatory gene
      expression of asthma-related cytokines in well-differentiated primary mouse
      tracheal epithelial (MTE) cell cultures. We hypothesized that simvastatin reduces
      the expression of IL-13-inducible genes in MTE cells. METHODS: We harvested
      tracheal epithelial cells from naive BALB/c mice, grew them under air-liquid
      interface (ALI) cell culture conditions, then assessed IL-13-induced gene
      expression in MTE cells using a quantitative real-time PCR mouse gene array kit.
      RESULTS: We found that simvastatin had differential effects on IL-13-mediated
      gene expression (inhibited eotaxin-1; MCP-1,-2,-3; and osteopontin (SPP1), while
      it induced caspase-1 and CCL20 (MIP-3alpha)) in MTE cells. For other asthma
      relevant genes such as TNF, IL-4, IL-10, CCL12 (MCP-5), CCL5 (RANTES), and CCR3,
      there were no significant IL-13-inducible or statin effects on gene expression.
      CONCLUSIONS: Simvastatin modulates the gene expression of selected IL-13
      inducible pro-inflammatory cytokines and chemokines in primary mouse tracheal
      epithelial cells. The airway epithelium may be a viable target tissue for the
      statin drugs. Further research is needed to assess the mechanisms of how statins
      modulate epithelial gene expression.

PMID- 22583377
TI  - Rhabdomyolysis and severe muscle weakness secondary to colistin therapy.
AB  - Rhabdomyolysis is a clinical condition that causes renal failure up to 40%.
      Rhabdomyolysis may be traumatic or nontraumatic. Colistin (polymyxin E) is an
      effective antibiotic. Nephrotoxicity is a frequently encountered side effect. The
      nephrotoxic effect of colistin is thought to be associated with increased
      membrane permeability, cell swelling and lysis, and the development of acute
      tubular necrosis. Here, we report a case of nontraumatic rhabdomyolysis
      associated with the use of colistin. There is only one report of rhabdomyolysis
      secondary to colistin in the literature, and there is no report of a case
      developing severe tetraparesis, as in our case.

PMID- 22583376
TI  - Cyclic-beta-glucans of Rhizobium (Sinorhizobium) sp. strain NGR234 are required
      for hypo-osmotic adaptation, motility, and efficient symbiosis with host plants.
AB  - Cyclic-beta-glucans (CbetaG) consist of cyclic homo-polymers of glucose that are
      present in the periplasmic space of many Gram-negative bacteria. A number of
      studies have demonstrated their importance for bacterial infection of plant and
      animal cells. In this study, a mutant of Rhizobium (Sinorhizobium) sp. strain
      NGR234 (NGR234) was generated in the cyclic glucan synthase (ndvB)-encoding gene.
      The great majority of CbetaG produced by wild-type NGR234 are negatively charged
      and substituted. The ndvB mutation abolished CbetaG biosynthesis. We found that,
      in NGR234, a functional ndvB gene is essential for hypo-osmotic adaptation and
      swimming, attachment to the roots, and efficient infection of Vigna unguiculata
      and Leucaena leucocephala.

PMID- 22583379
TI  - Zinc finger nucleases for targeted mutagenesis and repair of the sickle-cell
      disease mutation: An in-silico study.
AB  - BACKGROUND: Sickle cell disease (or simply, SCD) is an inherited hemoglobinopathy
      which is mostly prevalent among persons of African descent. SCD results from a
      monogenic (Hemoglobin, beta) point-mutation (substitution of the base Adenine
      with Thymine at position six) that leads to replacement of the amino acid
      glutamic acid (E) with valine (V). Management of SCD within resource-poor
      settings is largely syndromic, since the option of cure offered by bone-marrow
      transplantation (BMT) is risky and unaffordable by most affected individuals.
      Despite previous reports of repair and inhibition of the sickle beta-globin gene
      and messenger ribonucleic acids (mRNAs), respectively in erythrocyte precursor
      cells via gene-targeting using an oligomer-restriction enzyme construct and
      either ribozyme- or RNA-DNA chimeric oligonucleotides (or simply third strand
      binding), gene-therapy to treat SCD still remains largely preclinical. In the
      wake of the advances in target- gene- mutagenesis and repair wrought by zinc
      finger nuclease (ZFN) technology, it was hypothesized that SCD may be cured by
      the same. The goal of this study thus, was constructing a database of zinc finger
      arrays (ZFAs) and engineering ZFNs, that respectively bind and cleave within or
      around specific sequences in the sickle hemoglobin, beta (-betaS) gene. METHODS
      AND RESULTS: First, using the complete 1606 genomic DNA base pair (bp) sequences
      of the normal hemoglobin-beta (betaA) chain gene, and the ZiFiT-CoDA-ZFA software
      preset at default, 57 three-finger arrays (ZFAs) that specifically bind 9 base
      pair sequences within the normal hemoglobin-beta chain, were computationally
      assembled. Second, by serial linkage of these ZFAs to the Flavobacterium
      okeanokoites endonuclease Fok I- four ZFNs with unique specificity to >24 bp
      target-sequences at the genomic contextual positions 82, 1333, 1334, and 1413 of
      the betaA chain-gene were constructed in-silico. Third, localizing the point
      mutation of SCD at genomic contextual position -69-70-71- bp (a position
      corresponding to the 6th codon) of the betaA chain-gene, inspired the final
      design of five more ZFNs specific to >24 bp target-sequences within the 8,954 bp
      that are genomically adjacent to the 5' end of the betaA chain-gene. CONCLUSIONS:
      This set of 57 ZFAs and 9 ZFNs offers us gene-therapeutic precursors for the
      targeted mutagenesis and repair of the SCD mutation or genotype.

PMID- 22583380
TI  - The apes as reservoir of human pathogens.

PMID- 22583378
TI  - Mechanisms of pressure-diuresis and pressure-natriuresis in Dahl salt-resistant
      and Dahl salt-sensitive rats.
AB  - BACKGROUND: Data on blood flow regulation, renal filtration, and urine output in
      salt-sensitive Dahl S rats fed on high-salt (hypertensive) and low-salt
      (prehypertensive) diets and salt-resistant Dahl R rats fed on high-salt diets
      were analyzed using a mathematical model of renal blood flow regulation,
      glomerular filtration, and solute transport in a nephron. RESULTS: The mechanism
      of pressure-diuresis and pressure-natriuresis that emerges from simulation of the
      integrated systems is that relatively small increases in glomerular filtration
      that follow from increases in renal arterial pressure cause relatively large
      increases in urine and sodium output. Furthermore, analysis reveals the minimal
      differences between the experimental cases necessary to explain the observed
      data. It is determined that differences in renal afferent and efferent arterial
      resistances are able to explain all of the qualitative differences in observed
      flows, filtration rates, and glomerular pressure as well as the differences in
      the pressure-natriuresis and pressure-diuresis relationships in the three groups.
      The model is able to satisfactorily explain data from all three groups without
      varying parameters associated with glomerular filtration or solute transport in
      the nephron component of the model. CONCLUSIONS: Thus the differences between the
      experimental groups are explained solely in terms of difference in blood flow
      regulation. This finding is consistent with the hypothesis that, if a shift in
      the pressure-natriuresis relationship is the primary cause of elevated arterial
      pressure in the Dahl S rat, then alternation in how renal afferent and efferent
      arterial resistances are regulated represents the primary cause of chronic
      hypertension in the Dahl S rat.

PMID- 22583382
TI  - The art versus science of predicting prognosis: can a prognostic index predict
      short-term mortality better than experienced nurses do?
AB  - OBJECTIVE: To determine whether a prognostic index could predict one-week
      mortality more accurately than hospice nurses can. METHOD: An electronic health
      record-based retrospective cohort study of 21,074 hospice patients was conducted
      in three hospice programs in the Southeast, Northeast, and Midwest United States.
      Model development used logistic regression with bootstrapped confidence intervals
      and multiple imputation to account for missing data. The main outcome measure was
      mortality within 7 days of hospice enrollment. RESULTS: A total of 21,074
      patients were admitted to hospice between October 1, 2008 and May 31, 2011, and
      5562 (26.4%) died within 7 days. An optimal predictive model included the
      Palliative Performance Scale (PPS) score, admission from a hospital, and gender.
      The model had a c-statistic of 0.86 in the training sample and 0.84 in the
      validation sample, which was greater than that of nurses' predictions (0.72). The
      index's performance was best for patients with pulmonary disease (0.89) and worst
      for patients with cancer and dementia (both 0.80). The index's predictions of
      mortality rates in each index category were within 5.0% of actual rates, whereas
      nurses underestimated mortality by up to 18.9%. Using the optimal index threshold
      (<3), the index's predictions had a better c-statistic (0.78 versus 0.72) and
      higher sensitivity (74.4% versus 47.8%) than did nurses' predictions but a lower
      specificity (80.6% versus 95.1%). CONCLUSIONS: Although nurses can often identify
      patients who will die within 7 days, a simple model based on available clinical
      information offers improved accuracy and could help to identify those patients
      who are at high risk for short-term mortality.

PMID- 22583383
TI  - Corticosteroid-induced diabetes in palliative care.
AB  - BACKGROUND: Corticosteroids are one of the most commonly used medications in
      palliative care. Although the benefit of corticosteroids generally outweighs the
      risk in the palliative population, side effects are common and necessitate
      careful consideration prior to prescribing. In March of 2010, a guideline for
      monitoring blood glucose values was implemented as part of our standard care
      within our two inpatient tertiary palliative care units. METHOD: A retrospective
      study was conducted, the aim of which was twofold. First, we hoped to determine a
      prevalence rate for steroid-induced diabetes mellitus (SDM) in palliative care
      and whether or not screening glucose levels twice weekly was appropriate or
      required. Second, we wanted to determine if possible predictors existed for the
      development of SDM in a palliative population, thereby identifying the patients
      most at risk who would benefit from ongoing glucose monitoring. RESULTS AND
      DISCUSSION: We found that SDM is more common in palliative care patients than
      previously thought. Our study showed a higher likelihood of developing
      hyperglycaemia with higher doses of dexamethasone. But although dose is
      correlated with hyperglycemia, patients without high doses were also at risk.
      Further study is currently underway with slight modifications to the guideline to
      more accurately assess the physical burden, as well as the emotional and
      financial cost of a hyperglycemia screening protocol.

PMID- 22583384
TI  - Low testosterone levels are related to poor prognosis factors in men with
      prostate cancer prior to treatment.

PMID- 22583385
TI  - Effects of polymorphisms in the porcine microRNA MIR206 / MIR133B  cluster on
      muscle fiber and meat quality traits.
AB  - MicroRNAs are a class of small non-coding RNA molecules that repress gene
      expression primarily at the post-transcriptional level. Genetic variations in
      microRNA genes may contribute to phenotypic differences by altering the
      expression of microRNAs and their targets. Here, we identified 12 single
      nucleotide polymorphisms (SNPs) in the genomic region of the porcine MIR206 /
      MIR133B cluster, 10 and 2 of which were associated with MIR206 and MIR133B
      respectively. All 12 SNPs were located within primary microRNAs. Allele frequency
      determination in different pig breeds (Berkshire, n = 153; Landrace, n = 125;
      Yorkshire, n = 173) and association studies of muscle fiber characteristics, lean
      meat production and meat quality traits were performed on the MIR206 and MIR133B
      SNPs. The MIR206 SNPs were associated with the percentage of type IIa and IIb
      fibers for muscle fiber area composition, meat quality traits including drip loss
      and lightness, and backfat thickness, a parameter of lean meat production. In
      addition, we found significant association of the MIR133B SNPs with total muscle
      fiber number, loin eye area, and muscle pH. Furthermore, these SNPs significantly
      affected the levels of mature MIR206 and MIR133B , respectively, primarily by
      regulating the processing of primary microRNAs into precursor microRNAs.
      Interestingly, altered MIR206 levels correlated with phenotypic variability among
      genotypes of the MIR206 SNP. Our data suggest that polymorphisms in the porcine
      MIR206 / MIR133B cluster are a genetic factor affecting muscle and meat quality
      traits.

PMID- 22583386
TI  - Inherited platelet disorders and oral health.
AB  - Platelets play a key role in thrombosis and hemostasis. Accumulation of platelets
      at the site of vascular injury is the first step in the formation of hemostatic
      plugs, which play a pivotal role in preventing blood loss after injury. Platelet
      adhesion at sites of injury results in spreading, secretion, recruitment of
      additional platelets, and formation of platelet aggregates. Inherited platelet
      disorders are rare causes of bleeding syndromes, ranging from mild bruising to
      severe hemorrhage. The defects can reflect deficiency or dysfunction of platelet
      surface glycoproteins, granule contents, cytoskeletal proteins, platelet pro
      coagulant function, and signaling pathways. For instance, Bernard-Soulier
      syndrome and Glanzmann thrombasthenia are attributed to deficiencies of
      glycoprotein Ib/IX/V and GPIIb/IIIa, respectively, and are rare but severe
      platelet disorders. Inherited defects that impair platelet secretion and/or
      signal transduction are among the most common forms of mild platelet disorders
      and include gray platelet syndrome, Hermansky-Pudlak syndrome, and Chediak
      Higashi syndrome. When necessary, desmopressin, antifibrinolytic agents, and
      transfusion of platelets remain the most common treatment of inherited platelet
      disorders. Alternative therapies such as recombinant activated factor VII are
      also available for a limited number of situations. In this review, we will
      discuss the management of patients with inherited platelet disorders in various
      clinical situations related to dental cares, including surgical intervention.

PMID- 22583387
TI  - The impact of aging and atherosclerotic risk factors on transthoracic coronary
      flow reserve in subjects with normal coronary angiography.
AB  - Age may affect coronary flow reserve (CFR) especially in subjects with
      atherosclerotic risk factors (ARFs). The aim of this prospective, multicenter,
      observational study was to determine the effects of aging on CFR in patients with
      normal epicardial coronary arteries and ARFs. Three-hundred-thirty-five subjects
      (mean age = 61 years) with at least one ARF but normal coronary angiography
      underwent high-dose dipyridamole stress-echo with Doppler evaluation of left
      anterior descending artery. CFR was calculated as the ratio between hyperemic and
      resting coronary diastolic peak velocities. Patients were divided in age
      quartiles. CFR was progressively reduced with aging (1st quartile: 3.01 +/- 0.69,
      4th quartile: 2.39 +/- 0.49, p < 0.001). This was mainly due to a gradual
      increase of resting velocities (1st quartile = 26.3 +/- 6.1 cm/s, 4th quartile =
      30.2 +/- 6.4 cm/s, p < 0.001) while the reduction of hyperemic velocities
      remained unaffected (1st quartile = 77.7 +/- 18.9 cm/s, 4th quartile = 70.9 +/-
      18.4 cm/s, NS). When age quartiles and ARFs were entered into a regression model,
      third and fourth age quartile (p < 0.0005 and p < 0.0001 respectively), left
      ventricular mass index (p < 0.0001), diastolic blood pressure (p < 0.001), total
      cholesterol (p < 0.002), fasting blood glucose (p < 0.01) and male gender (p <
      0.05) were independent determinants of CFR in the whole population. Aging reduces
      coronary flow reserve in patients with angiographically normal coronary arteries
      due to a gradual increase of resting coronary flow velocity. CFR is also affected
      by atherosclerotic risk factors and left ventricular hypertrophy.

PMID- 22583388
TI  - Forensic analysis of mtDNA haplotypes from two rural communities in Haiti
      reflects their population history.
AB  - Very little genetic data exist on Haitians, an estimated 1.2 million of whom, not
      including illegal immigrants, reside in the United States. The absence of genetic
      data on a population of this size reduces the discriminatory power of criminal
      and missing-person DNA databases in the United States and Caribbean. We present a
      forensic population study that provides the first genetic data set for Haiti.
      This study uses hypervariable segment one (HVS-1) mitochondrial DNA (mtDNA)
      nucleotide sequences from 291 subjects primarily from rural areas of northern and
      southern Haiti, where admixture would be minimal. Our results showed that the
      African maternal genetic component of Haitians had slightly higher West-Central
      African admixture than African-Americans and Dominicans, but considerably less
      than Afro-Brazilians. These results lay the foundation for further forensic
      genetics studies in the Haitian population and serve as a model for forensic
      mtDNA identification of individuals in other isolated or rural communities.

PMID- 22583389
TI  - Uterine infection influences size and follicular fluid composition of the largest
      follicle in buffalo (Bubalus bubalis).
AB  - The effect of uterine infection on size and follicular fluid composition of the
      largest follicle was studied in buffalo. Reproductive tracts were collected from
      102 graded Murrah buffaloes at an abattoir. Uterine infection was diagnosed by
      physical examination of uterine mucus, white side test and uterine cytology.
      Samples with pus-containing mucus, positive reaction on white side test and/or
      >5% neutrophils were considered to be positive for uterine infection. Diameter of
      the largest follicle was measured, and follicular fluid was aspirated and assayed
      for nitric oxide (NO), ascorbic acid (AA), cholesterol, oestradiol (E(2)) and
      progesterone (P(4)). Infected buffaloes had smaller-sized (p < 0.0001) largest
      follicles than non-infected buffaloes. Follicular fluid collected from the
      largest follicle in infected buffaloes had greater (p < 0.0001) NO and P(4)
      concentrations coincident with lesser AA (p < 0.001), cholesterol (p < 0.0001)
      and E(2) (p < 0.0001) concentrations. Results indicated that uterine infection
      has an inhibitory effect on growth of the largest follicle in buffalo. The
      changes in follicular fluid composition in infected buffaloes suggest that the
      direct effect of uterine infection on ovarian function may be mediated through an
      alteration in the follicular microenvironment. Greater NO and lesser AA
      concentrations in the follicular fluid of infected animals are novel findings.

PMID- 22583390
TI  - Skin and subcutaneous thickness at injecting sites in children with diabetes:
      ultrasound findings and recommendations for giving injection.
AB  - BACKGROUND: Children who inject insulin need clear guidelines as to the length of
      needle best for them. We studied the distance from surface to muscle in children
      in order to make needle choices which are evidence-based. METHODS: One hundred
      one children with type 1 diabetes were divided into three groups according to
      age: 2-6, 7-13, and 14-17 yr. The thickness of skin and subcutaneous (SC) tissue
      was measured by ultrasound in all injection sites. RESULTS: Skin thickness varied
      from 1.58 mm in the arm of the youngest children to 2.29 mm in the buttocks of
      the adolescents. Values decreased progressively based on age (2-6 < 7-13 < 14-17)
      and on body site (arm < thigh < abdomen < buttocks). Skin + SC thickness varied
      in a similar fashion. The skin surface to muscle distances were <4 mm in nearly
      10% of children, especially in the 2-6 yr group. In this group, the rate of
      intramuscular (IM) injections using the 4-mm pen needle when a pinch-up is not
      used would be 20.2%. This rate of IM injections doubles when using the 5-mm
      needle, and when injections are given under similar conditions it triples using
      the 6-mm needle. CONCLUSIONS: It seems medically appropriate for all children to
      use short needles where possible to minimize inadvertent IM injections which may
      increase glycemic variability. Currently, the safest needle for all children
      appears to be the 4-mm pen needle. However, when used in children aged 2-6 yr, it
      should be used with a pinched skin fold.

PMID- 22583391
TI  - Incidence and risk factors for post-traumatic hydrocephalus following
      decompressive craniectomy for intractable intracranial hypertension and
      evacuation of mass lesions.
AB  - There continues to be a considerable interest in decompressive craniectomy in the
      management of severe traumatic brain injury (TBI). Though technically
      straightforward, the procedure is not without significant complications. In this
      study we assessed the incidence and risk factors for the development of subdural
      hygroma and hydrocephalus after decompressive craniectomy. A total of 195
      patients who had had a decompressive craniectomy for severe TBI between 2004 and
      2010 at the two major trauma centers in Western Australia were considered. Of the
      166 patients who survived after the acute hospital stay, 93 (56%; 95% confidence
      interval [CI] 48,63%) developed subdural hygroma; 45 patients (48%) had
      unilateral and 48 patients (52%) had bilateral subdural hygromas. Of the 159
      patients who survived more than 6 months after surgery, 72 (45%; 95% CI 38,53%)
      developed radiological evidence of ventriculomegaly, and 26 of these 72 patients
      (36%; 95% CI 26,48%) developed clinical evidence of hydrocephalus and required a
      ventriculoperitoneal (VP) shunt. Maximum intracranial pressure prior to
      decompression (p=0.005), subdural hygroma (p=0.012), and a lower admission
      Glasgow Coma Scale score (p=0.009), were significant risk factors for
      hydrocephalus after decompressive craniectomy. Hydrocephalus requiring a VP shunt
      was associated with a higher risk of unfavorable neurological outcomes at 18
      months (odds ratio 7.46; 95%CI 1.17,47.4; p=0.033), after adjusting for other
      factors. Our results showed a clear association between injury severity, subdural
      hygroma, and hydrocephalus, suggesting that damage to the cerebrospinal fluid
      drainage pathways contributes to the primary brain injury rather than the margin
      of the craniectomy as the factor responsible for these complications.

PMID- 22583392
TI  - Prediction of organ toxicity endpoints by QSAR modeling based on precise chemical
      histopathology annotations.
AB  - The ability to accurately predict the toxicity of drug candidates from their
      chemical structure is critical for guiding experimental drug discovery toward
      safer medicines. Under the guidance of the MetaTox consortium (Thomson Reuters,
      CA, USA), which comprised toxicologists from the pharmaceutical industry and
      government agencies, we created a comprehensive ontology of toxic pathologies for
      19 organs, classifying pathology terms by pathology type and functional organ
      substructure. By manual annotation of full-text research articles, the ontology
      was populated with chemical compounds causing specific histopathologies.
      Annotated compound-toxicity associations defined histologically from rat and
      mouse experiments were used to build quantitative structure-activity relationship
      models predicting subcategories of liver and kidney toxicity: liver necrosis,
      liver relative weight gain, liver lipid accumulation, nephron injury, kidney
      relative weight gain, and kidney necrosis. All models were validated using two
      independent test sets and demonstrated overall good performance: initial
      validation showed 0.80-0.96 sensitivity (correctly predicted toxic compounds) and
      0.85-1.00 specificity (correctly predicted non-toxic compounds). Later validation
      against a test set of compounds newly added to the database in the 2 years
      following initial model generation showed 75-87% sensitivity and 60-78%
      specificity. General hepatotoxicity and nephrotoxicity models were less accurate,
      as expected for more complex endpoints.

PMID- 22583393
TI  - Mechanism for activation of triosephosphate isomerase by phosphite dianion: the
      role of a hydrophobic clamp.
AB  - The role of the hydrophobic side chains of Ile-172 and Leu-232 in catalysis of
      the reversible isomerization of R-glyceraldehyde 3-phosphate (GAP) to
      dihydroxyacetone phosphate (DHAP) by triosephosphate isomerase (TIM) from
      Trypanosoma brucei brucei (Tbb) has been investigated. The I172A and L232A
      mutations result in 100- and 6-fold decreases in k(cat)/K(m) for the
      isomerization reaction, respectively. The effect of the mutations on the product
      distributions for the catalyzed reactions of GAP and of [1-(13)C]-glycolaldehyde
      ([1-(13)C]-GA) in D(2)O is reported. The 40% yield of DHAP from wild-type Tbb TIM
      catalyzed isomerization of GAP with intramolecular transfer of hydrogen is found
      to decrease to 13% and to 4%, respectively, for the reactions catalyzed by the
      I172A and L232A mutants. Likewise, the 13% yield of [2-(13)C]-GA from
      isomerization of [1-(13)C]-GA in D(2)O is found to decrease to 2% and to 1%,
      respectively, for the reactions catalyzed by the I172A and L232A mutants. The
      decrease in the yield of the product of intramolecular transfer of hydrogen is
      consistent with a repositioning of groups at the active site that favors transfer
      of the substrate-derived hydrogen to the protein or the oxygen anion of the bound
      intermediate. The I172A and L232A mutations result in (a) a >10-fold decrease
      (I172A) and a 17-fold increase (L232A) in the second-order rate constant for the
      TIM-catalyzed reaction of [1-(13)C]-GA in D(2)O, (b) a 170-fold decrease (I172A)
      and 25-fold increase (L232A) in the third-order rate constant for phosphite
      dianion (HPO(3)(2-)) activation of the TIM-catalyzed reaction of GA in D(2)O, and
      (c) a 1.5-fold decrease (I172A) and a larger 16-fold decrease (L232A) in K(d) for
      activation of TIM by HPO(3)(2-) in D(2)O. The effects of the I172A mutation on
      the kinetic parameters for the wild-type TIM-catalyzed reactions of the whole
      substrate and substrate pieces are consistent with a decrease in the basicity of
      the carboxylate side chain of Glu-167 for the mutant enzyme. The data provide
      striking evidence that the L232A mutation leads to a ca. 1.7 kcal/mol
      stabilization of a catalytically active loop-closed form of TIM (E(C)) relative
      to an inactive open form (E(O)).

PMID- 22583395
TI  - Surgical correction of nephrogenic ascites in a renal transplant recipient.
AB  - The unusual development of massive ascites, 3 years after renal transplant,
      caused by undefined, innate renal allograft pathology is described. Challenges of
      surgical correction of this problem, allowing for salvage of the allograft, are
      reviewed.

PMID- 22583396
TI  - Expression of proinflammatory factors in renal cortex induced by methylmalonic
      acid.
AB  - BACKGROUND: Methylmalonic aciduria is an inborn error of metabolism that causes
      renal failure and tubulointerstitial (TI) nephritis as complications. This study
      aimed to examine the levels of expression of several genes related to
      inflammation, oxidative stress, and mitochondrial function in the renal cortex of
      rats receiving methylmalonic acid (MMA). METHODS: Rats received MMA
      subcutaneously for a month. Tumor necrosis factor alpha (TNFalpha), nuclear
      factor-kappa B, interleukin 1 beta (IL-1beta), and cyclooxygenase 2 (COX-2) genes
      were examined by real-time polymerase chain reaction. We also examined
      transforming growth factor beta (TGF-beta) related to TI fibrosis, c-FOS,
      belonging to the immediate early gene family of transcription factors, and
      expression of SIRT1, related to energy production. RESULTS: There was
      significantly higher expression of TNFalpha and a trend toward a higher level of
      TGF-beta transcripts in the methylmalonic model group compared with the controls.
      However, SIRT1 expression was not different among the groups. Urinary MMA
      excretion correlated positively with mRNA level of TGF-beta. The expression of
      COX-2 was positively associated with the expression of c-FOS and inversely
      related to the expression of IL-1beta. CONCLUSIONS: The higher levels of TNFalpha
      and TGF-beta transcripts suggest inflammation and differentiation processes in
      the renal cortex in rats because of MMA. After 1 month of MMA injections,
      expression levels of SIRT1 were not affected, suggesting mitochondrial
      preservation in early stages of the disease.

PMID- 22583397
TI  - Acute fulminant pseudomembranous colitis which developed after ileostomy closure
      and required emergent total colectomy: a case report.
AB  - INTRODUCTION: Pseudomembranous colitis is known to be caused by Clostridium
      difficile; and, in 3% to 8% of patients, it lapses into an aggressive clinical
      course that is described as fulminant. We present here a case of extremely rapid
      and fatal fulminant pseudomembranous colitis that developed after ileostomy
      closure, a minor surgical procedure. To the best of our knowledge, this is the
      first case report of fatal fulminant pseudomembranous colitis after closure of a
      diversion ileostomy in an adult. CASE PRESENTATION: A 69-year-old Japanese man,
      who had previously undergone low anterior resection and creation of a diverting
      ileostomy for stage III rectal carcinoma was admitted for ileostomy closure.
      Preoperatively, he received oral kanamycin and metronidazole along with
      parenteral cefmetazole. His surgery and postoperative course were uneventful
      until the third postoperative day, when fever and watery diarrhea became
      apparent. The next day he presented with epigastric and left lower abdominal
      pain. Computed tomography revealed a slightly distended colon. Later that night,
      his blood pressure fell and intravenous infusion was started. In the early
      morning of the fifth postoperative day, his blood pressure could be maintained
      only with a vasopressor. Follow-up computed tomography demonstrated severe
      colonic dilation. A colonoscopy confirmed the presence of pseudomembranous
      colitis, and so oral vancomycin was administered immediately. However, within
      three hours of the administration, his condition rapidly deteriorated into shock.
      Although an emergent total colectomy with creation of an end ileostomy was
      performed, our patient died 26 hours after the surgery. The histopathological
      examination was consistent with pseudomembranous colitis. CONCLUSION: It is
      important to recognize that, although rare, there is a type of extremely
      aggressive pseudomembranous colitis in which the usual waiting period for medical
      treatment might be lethal. We consider that colonoscopy and computed tomography
      are helpful to decide the necessity of emergent surgical treatment without delay.

PMID- 22583394
TI  - Adiposity, hormone replacement therapy use and breast cancer risk by age and
      hormone receptor status: a large prospective cohort study.
AB  - INTRODUCTION: Associations of hormone-receptor positive breast cancer with excess
      adiposity are reasonably well characterized; however, uncertainty remains
      regarding the association of body mass index (BMI) with hormone-receptor negative
      malignancies, and possible interactions by hormone replacement therapy (HRT) use.
      METHODS: Within the European EPIC cohort, Cox proportional hazards models were
      used to describe the relationship of BMI, waist and hip circumferences with risk
      of estrogen-receptor (ER) negative and progesterone-receptor (PR) negative (n =
      1,021) and ER+PR+ (n = 3,586) breast tumors within five-year age bands. Among
      postmenopausal women, the joint effects of BMI and HRT use were analyzed.
      RESULTS: For risk of ER-PR- tumors, there was no association of BMI across the
      age bands. However, when analyses were restricted to postmenopausal HRT never
      users, a positive risk association with BMI (third versus first tertile HR = 1.47
      (1.01 to 2.15)) was observed. BMI was inversely associated with ER+PR+ tumors
      among women aged <=49 years (per 5 kg/m2 increase, HR = 0.79 (95%CI 0.68 to
      0.91)), and positively associated with risk among women >=65 years (HR = 1.25
      (1.16 to 1.34)). Adjusting for BMI, waist and hip circumferences showed no
      further associations with risks of breast cancer subtypes. Current use of HRT was
      significantly associated with an increased risk of receptor-negative (HRT current
      use compared to HRT never use HR: 1.30 (1.05 to 1.62)) and positive tumors (HR:
      1.74 (1.56 to 1.95)), although this risk increase was weaker for ER-PR- disease
      (Phet = 0.035). The association of HRT was significantly stronger in the leaner
      women (BMI <=22.5 kg/m2) than for more overweight women (BMI >=25.9 kg/m2) for,
      both, ER-PR- (HR: 1.74 (1.15 to 2.63)) and ER+PR+ (HR: 2.33 (1.84 to 2.92))
      breast cancer and was not restricted to any particular HRT regime. CONCLUSIONS:
      An elevated BMI may be positively associated with risk of ER-PR- tumors among
      postmenopausal women who never used HRT. Furthermore, postmenopausal HRT users
      were at an increased risk of ER-PR- as well as ER+PR+ tumors, especially among
      leaner women. For hormone-receptor positive tumors, but not for hormone-receptor
      negative tumors, our study confirms an inverse association of risk with BMI among
      young women of premenopausal age. Our data provide evidence for a possible role
      of sex hormones in the etiology of hormone-receptor negative tumors.

PMID- 22583399
TI  - Polyphenols counteract tumor cell chemoresistance conferred by multidrug
      resistance proteins.
AB  - One of the main reasons of cancer resistance to chemotherapeutic treatment is the
      presence of different ABC multidrug transporters in plasma membranes. The
      transporters extrude wide spectrum of anticancer agents out of cancer cells at
      the expense of energy derived from ATP-hydrolysis. Plant-origin polyphenolic
      compounds, mainly flavonoids and stilbenes or their synthetic derivatives, can
      modulate the main ABC transporters responsible for cancer drug resistance,
      including P-glycoprotein, MRP1 and BCRP. The recent studies on different
      resistant cancer cell lines enabled the discovery of a number of polyphenolic
      compounds able to reverse drug resistance in vitro and these compounds could be
      promising candidates for further clinical trials. The review summarizes the
      recent advances in the field of polyphenols interaction with ATP-binding cassette
      multidrug transporters. The mechanism of flavonoids interactions with the
      multidrug transporters and the structure-activity relationship are also
      discussed.

PMID- 22583398
TI  - Differential requirement of cyclin-dependent kinase 2 for oligodendrocyte
      progenitor cell proliferation and differentiation.
AB  - Cyclin-dependent kinases (Cdks) and their cyclin regulatory subunits control
      cell growth and division. Cdk2-cyclin E complexes, phosphorylating the
      retinoblastoma protein, drive cells through the G1/S transition into the S phase
      of the cell cycle. Despite its fundamental role, Cdk2 was found to be
      indispensable only in specific cell types due to molecular redundancies in its
      function. Converging studies highlight involvement of Cdk2 and associated cell
      cycle regulatory proteins in oligodendrocyte progenitor cell proliferation and
      differentiation. Giving the contribution of this immature cell type to brain
      plasticity and repair in the adult, this review will explore the requirement of
      Cdk2 for oligodendrogenesis, oligodendrocyte progenitor cells proliferation and
      differentiation during physiological and pathological conditions.

PMID- 22583400
TI  - Natural polyphenols properties: chemopreventive and chemosensitizing activities.

PMID- 22583401
TI  - Natural compounds as cancer chemopreventive and chemotherapeutic agents: insights
      gained from mechanistic and pharmacologic studies.

PMID- 22583403
TI  - Chemoprevention of breast cancer by dietary compounds.
AB  - Breast cancer is the leading cause of cancer-related deaths in women in the
      United States and many other countries. There is an immediate need for more
      effective and less toxic therapeutic and preventive strategies for many cancers,
      especially for breast cancer. Natural products are being tested with a hope of
      identifying novel potent molecules as anticancer agents. Phytochemicals and
      dietary compounds have been used for the treatment of various illnesses
      throughout history due to their safety, low toxicity, and general availability.
      Currently, many active phytochemicals are in clinical trials. Preclinical and
      clinical studies have indicated that daily consumption of dietary phytochemicals
      reduces the risk of several cancers. Phytochemicals can inhibit, delay, or
      reverse carcinogenesis by inducing detoxifying and antioxidant enzymes, by
      regulating inflammatory/proliferative signaling pathways, and by inducing
      apoptosis. This review article describes some of the potential natural cancer
      preventive compounds, along with a mechanistic discussion of their interactions
      with key cellular signal transduction pathways as well as their contribution to
      the suppression of breast cancer cell growth.

PMID- 22583405
TI  - Anti-cancer and other bioactivities of Korean Angelica gigas Nakai (AGN) and its
      major pyranocoumarin compounds.
AB  - Korean Angelica gigas Nakai (AGN) is a major medicinal herb used in Asian
      countries such as Korea and China. Traditionally, its dried root has been used to
      treat anemia, pain, infection and articular rheumatism in Korea, most often
      through boiling in water to prepare the dosage forms. The pyranocoumarin compound
      decursin and its isomer decursinol angelate (DA) are the major chemical
      components in the alcoholic extracts of the root of AGN. The in vitro anti-tumor
      activities of decursin and/or DA against prostate cancer, lung cancer, breast
      cancer, colon cancer, bladder cancer, sarcoma, myeloma and leukemia have been
      increasingly reported in the past decade whereas the in vivo efficacy in mouse
      models was established only for a few organ sites. Preliminary pharmacokinetic
      studies by us and others in rodent models indicated that decursinol (DOH), which
      has much less in vitro direct anticancer activities by itself, is the major and
      rapid in vivo hydrolysis metabolite of both decursin and DA. Besides decursin, DA
      and DOH, other chemical components in AGN such as polysaccharides and
      polyacetylenes have been reported to exert anti-cancer and anti-inflammation
      activities as well. We systematically reviewed the published literature on the
      anti-cancer and other bio-activities effects of AGN extract and decursin, DA and
      DOH, as well as other chemicals identified from AGN. Although a number of areas
      are identified that merit further investigation, one critical need is first-in
      human studies of the pharmacokinetics of decursin/DA to determine whether humans
      differ from rodents in absorption and metabolism of these compounds.

PMID- 22583404
TI  - Unifying mechanisms of action of the anticancer activities of triterpenoids and
      synthetic analogs.
AB  - Triterpenoids such as betulinic acid (BA) and synthetic analogs of oleanolic acid
      [2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO)] and glycyrrhetinic acid [2
      cyano-3,11-dioxo-18beta-oleana-1,12-dien-30-oc acid (CDODA)] are potent
      anticancer agents that exhibit antiproliferative, antiangiogenic, anti
      inflammatory and pro-apoptotic activities. Although their effects on multiple
      pathways have been reported, unifying mechanisms of action have not been
      reported. Studies in this laboratory have now demonstrated that several
      triterpenoids including BA and some derivatives, celastrol, methyl ursolate, beta
      boswellic acid derivatives, and the synthetic analogs CDDO, CDODA and their
      esters decreased expression of specificity protein (Sp) transcription factors and
      several pro-oncogenic Sp-regulated genes in multiple cancer cell lines. The
      mechanisms of this response are both compound- and cell context-dependent and
      include activation of both proteasome-dependent and -independent pathways.
      Triterpenoid-mediated induction of reactive oxygen species (ROS) has now been
      characterized as an important proteasome-independent pathway for downregulation
      of Sp transcription factors. ROS decreases expression of microRNA-27a (miR-27a)
      and miR-20a/miR-17-5p and this results in the induction of the transcriptional
      "Sp-repressors" ZBTB10 and ZBTB4, respectively, which in turn downregulate Sp and
      Sp-regulated genes. Triterpenoids also activate or deactive nuclear receptors and
      G-protein coupled receptors, and these pathways contribute to their
      antitumorigenic activity and may also play a role in targeting Sp1, Sp3 and Sp4
      which are highly overexpressed in multiple cancers and appear to be important for
      maintaining the cancer phenotype.

PMID- 22583406
TI  - The cancer preventive effects of edible mushrooms.
AB  - An increasing body of scientific literature suggests that dietary components may
      exert cancer preventive effects. Tea, soy, cruciferous vegetables and other foods
      have been investigated for their cancer preventive potential. Some non-edible
      mushrooms like Reishi (Ganoderma lucidum) have a history use, both alone and in
      conjunction with standard therapies, for the treatment of various diseases
      including cancer in some cultures. They have shown efficacy in a number of
      scientific studies. By comparison, the potential cancer preventive effects of
      edible mushrooms have been less well-studied. With similar content of putative
      effective anticancer compounds such as polysaccharides, proteoglycans, steroids,
      etc., one might predict that edible mushrooms would also demonstrate anticancer
      and cancer preventive activity. In this review, available data for five commonly
      consumed edible mushrooms: button mushrooms (Agaricus bisporus), A. blazei,
      oyster mushrooms (Pleurotus ostreatus), shiitake mushrooms (Lentinus edodes), and
      maitake (Grifola frondosa) mushrooms is discussed. The results of animal model
      and human intervention studies, as well as supporting in vitro mechanistic
      studies are critically evaluated. Weaknesses in the current data and topics for
      future work are highlighted.

PMID- 22583402
TI  - Cancer prevention with promising natural products: mechanisms of action and
      molecular targets.
AB  - Cancer is the second leading cause of death worldwide. There is greater need for
      more effective and less toxic therapeutic and preventive strategies. Natural
      products are becoming an important research area for novel and bioactive
      molecules for drug discovery. Phytochemicals and dietary compounds have been used
      for the treatment of cancer throughout history due to their safety, low toxicity,
      and general availability. Many active phytochemicals are in human clinical
      trials. Studies have indicated that daily consumption of dietary phytochemicals
      have cancer protective effects against carcinogens. They can inhibit, delay, or
      reverse carcinogenesis by inducing detoxifying and antioxidant enzymes systems,
      regulating inflammatory and proliferative signaling pathways, and inducing cell
      cycle arrest and apoptosis. Epidemiological studies have also revealed that high
      dietary intakes of fruits and vegetables reduce the risk of cancer. This review
      discusses potential natural cancer preventive compounds, their molecular targets,
      and their mechanisms of actions.

PMID- 22583409
TI  - Developing phytoestrogens for breast cancer prevention.
AB  - Breast cancer is one of the most common types of cancer in women, and is the
      second leading cause of cancer-related deaths in the United States.
      Chemoprevention using phytoestrogens (PEs) for breast cancer may be a valid
      strategy. PEs are phytochemicals with estrogen-like structures and can be
      classified into four types: isoflavones, lignans, stilbenes and coumestans. They
      are widely distributed in diet and herbs and have shown anti-cancer activity via
      mechanisms including estrogen receptor modulation, aromatase inhibition, and anti
      angiogenesis. Genistein, daidzein and resveratrol are some of the most studied PE
      examples. Quality control in product manufacturing and clinical study design is a
      critical issue in developing them as clinically effective chemopreventive agents
      for breast cancer.

PMID- 22583407
TI  - Bioavailability and pharmacokinetics of genistein: mechanistic studies on its
      ADME.
AB  - Genistein, one of the most active natural flavonoids, exerts various biological
      effects including chemoprevention, antioxidation, antiproliferation and
      anticancer. More than 30 clinical trials of genistein with various disease
      indications have been conducted to evaluate its clinical efficacy. Based on many
      animals and human pharmacokinetic studies, it is well known that the most
      challenge issue for developing genistein as a chemoprevention agent is the low
      oral bioavailability, which may be the major reason relating to its ambiguous
      therapeutic effects and large interindividual variations in clinical trials. In
      order to better correlate pharmacokinetic to pharmacodynamics results in animals
      and clinical studies, an in-depth understanding of pharmacokinetic behavior of
      genistein and its ADME properties are needed. Numerous in vitro/in vivo ADME
      studies had been conducted to reveal the main factors contributing to the low
      oral bioavailability of genistein. Therefore, this review focuses on summarizing
      the most recent progress on mechanistic studies of genistein ADME and provides a
      systemic view of these processes to explain genistein pharmacokinetic behaviors
      in vivo. The better understanding of genistein ADME property may lead to
      development of proper strategy to improve genistein oral bioavailability via
      mechanism-based approaches.

PMID- 22583411
TI  - The nuclear orphan receptors NR4A as therapeutic target in cancer therapy.
AB  - NR4A1 (Nur77), NR4A2 (Nurr1) and NR4A3 (Nor-1) are three members of the orphan
      nuclear receptor (NR) family referred to as NR4A family. This subgroup activates
      gene expression in a constitutive ligand-independent manner. These nuclear
      receptors are classified as early response genes that are induced by a diverse
      range of signals. These orphan NRs have been implicated in cell cycle regulation,
      apoptosis, inflammation, metabolism and more recently in carcinogenesis. The
      ultimate growth of a tumor depends not only on the rate of tumor cell
      proliferation, but also the rate of apoptosis and NR4A1 controls both, survival
      and death of cancer cells. It has been demonstrated that NR4A1 activities are
      regulated through its subcellular localisation. In the nucleus, NR4A1 can
      function in a context dependent manner either as an oncogenic survival factor,
      promoting cancer cell growth or as the opposite through the activation of
      apoptosis. Additionally, in an atypical fashion, it is a potent killer when
      migrating to the mitochondria, where it binds to Bcl-2 and converts its survival
      phenotype, triggering cytochrome c release and apoptosis. The most convincing
      evidence that nuclear orphan receptors function as critical tumor suppressors is
      the observation that the NR4A1 and NR4A3 double knock out mouse develops rapidly
      acute myeloid leukemia. Down regulation of NR4A1 and NR4A3 was a common feature
      in leukemic blasts from human AML patients. In particular, the recent
      identification of pro-apoptotic agents inducing NR4A expression or acting as
      agonists suggests that these members could serve as potential targets for cancer
      therapy.

PMID- 22583412
TI  - Calculation of molecular features with apparent impact on both activity of
      mutagens and activity of anticancer agents.
AB  - The analysis of the influence of molecular features which can be extracted from
      the simplified molecular input line entry system (SMILES) and involved in the
      process of the building up of a series of QSAR models (with different splits into
      training and test sets) by means of the CORAL software for mutagenicity and
      anticancer activity has been performed. The presence of nitrogen (sp3) is
      favorable for decrease of the both endpoints; the presence of only one ring is
      also promotor for decrease of the both endpoints; however the presence of two or
      three rings is favorable for increase of mutagenicity and decrease of anticancer
      activity. These findings provide useful criteria for further experimental and
      computational studies in the search for new anticancer agents.

PMID- 22583413
TI  - Anti-metastatic and anti-angiogenic properties of potential new anti-cancer drugs
      based on metal complexes of selenosemicarbazones.
AB  - Our previous studies showed that zinc (II), cadmium (II) and nickel (II)
      complexes with 2-formylpyridine selenosemicarbazone induce apoptosis in cancer
      cells via activation of mitochondrial pathway. Herein, we reported their
      antimetastatic properties. Nickel (II), and zinc (II) complexes exhibited the
      strongest inhibitory potential towards MMP-2/9, while all investigated compounds
      significantly decreased proteolytic activity of MMP-2/9 in human breast cancer
      MDA-MB-361 cells. As shown by in vitro transmembrane assays, nickel (II) complex
      was the most effective in inhibiting invasion of MDA-MB-361 cells, while the
      cadmium (II) complex was the most active in inhibiting HeLa cells invasion. In
      malignant cells, the complexes inhibited intracellular accumulation of reactive
      oxygen species, known for its pro-angiogenic properties via VEGF signaling, but
      no reduction in total cellular amount of VEGF was found. Furthermore,
      tubulogenesis test showed anti-angiogenic effect of the complexes in treated
      endothelial cells. Data indicate multiple mechanisms of the complexes' anti
      angiogenic properties. In addition, they could modulate metastatic phenotype of
      tumor cells. Nickel (II) complex with 2-formylpyridine selenosemicarbazone
      revealed to be the most potent.

PMID- 22583414
TI  - The role of peroxisome proliferator-activated receptor-gamma in breast cancer.
AB  - Peroxisome Proliferator-Activated Receptor-gamma (PPARgamma) is an extensively
      studied ligand-activated nuclear hormone receptor that functions as transcription
      factor and plays an important role in diverse biological processes, such as lipid
      metabolism and insulin sensitization. Recent studies have demonstrated that
      PPARgamma is over-expressed in many tumor types, including breast cancer,
      suggesting a possible role in tumor development and/or progression and a putative
      prognostic value. Moreover, naturally-occurring and synthetic PPARgamma agonists
      promote growth inhibition, apoptosis and differentiation of tumor cells. The
      present review summarizes the available information on PPARgamma expression in
      breast tumors and the use of PPARgamma ligands as anti-cancer agents for breast
      cancer treatment, both in vitro and in vivo. Considering the data so far,
      specific PPARgamma agonists seem to exert beneficial effects against breast
      cancer and may therefore represent potential therapeutic agents.

PMID- 22583408
TI  - Plants vs. cancer: a review on natural phytochemicals in preventing and treating
      cancers and their druggability.
AB  - Cancer remains to be one of the leading causes of death in the United States and
      around the world. The advent of modern drug-targeted therapies has undeniably
      improved cancer patients' cares. However, advanced metastasized cancer remains
      untreatable. Hence, continued searching for a safer and more effective
      chemoprevention and treatment is clearly needed for the improvement of the
      efficiency and to lower the treatment cost for cancer care. Cancer
      chemoprevention with natural phytochemical compounds is an emerging strategy to
      prevent, impede, delay, or cure cancer. This review summarizes the latest
      research in cancer chemoprevention and treatment using the bioactive components
      from natural plants. Relevant molecular mechanisms involved in the
      pharmacological effects of these phytochemicals are discussed. Pharmaceutical
      developmental challenges and opportunities in bringing the phytochemicals into
      the market are also explored. The authors wish to expand this research area not
      only for their scientific soundness, but also for their potential druggability.

PMID- 22583410
TI  - Prevention of colitis-associated cancer: natural compounds that target the IL-6
      soluble receptor.
AB  - The risk of developing colorectal cancer increases in patients with inflammatory
      bowel disease (IBD) and a growing body of evidence shows the critical role of
      interleukin (IL-6) in this process. IL-6 is both a pro- and anti-inflammatory
      cytokine whose effects are mediated through activation of STAT3. Recent studies
      have also demonstrated that IL-6 trans-signaling through its soluble receptor
      occurs in IBD and cancer. IL-6 trans-signaling therefore is emerging as an
      attractive approach to diminish the inflammatory signals in conditions of chronic
      inflammation. The purpose of cancer chemoprevention is to either delay the onset
      or progression from precancerous lesions. Natural compounds because of their low
      toxicity render themselves excellent candidates that can be administered over the
      lifetime of an individual. With the focus of managing IBD over a long time and
      preventing onset of colitis-associated cancer, we believe that there should be
      increased research focus on identifying chemopreventive compounds that can render
      themselves to long term use possibly for the lifetime of predisposed individuals.
      Here, we review the role of IL-6 signaling in IBD and colitis-associated cancer
      and underscore the importance of searching for natural compounds that would
      target the IL-6 trans-signaling pathway as a way to diminish chronic inflammatory
      conditions in the gastrointestinal tract and possibly hamper the progression to
      colon cancer. We propose that effective screening and identification of natural
      chemopreventive compounds that target IL-6 trans-signaling has important
      implications for the development of optimal strategies against cancer development
      triggered by inflammation.

PMID- 22583415
TI  - Dual roles of sulforaphane in cancer treatment.
AB  - Sulforaphane (SFN), one of naturally occurring isothiocyanates (ITCs), has huge
      cancer chemopreventive potential. It modulates cell death, cell cycle,
      angiogenesis, susceptibility to carcinogens, invasion and metastasis and
      possesses antioxidant activities. It functions as an inhibitor of phase I enzymes
      and also as an inducer of phase II detoxification enzymes through different ways.
      NF-E2- related factor-2(Nrf-2), as well as mitogen-activated protein kinase
      (MAPK), is regulated by SFN. Intriguingly, strong evidence has showed the dark
      side of Nrf-2: stable upregulation of Nrf-2-mediated survival pathway would
      protect cancer cells from a subset of chemotherapeutic agents tested. This
      suggested that overexpression of Nrf-2 resulted in enhanced resistance of cancer
      cells to chemotherapeutic agents. Hence, future studies will focus on clarifying
      the exact time and dose of SFN to modulate the Nrf-2 signal pathway during
      chemotherapy and the efficacy of coadministration of Nrf-2 modulators during
      chemotherapy in order to make full use of the beneficial effect of this agent
      while eliminating the potential side effects.

PMID- 22583416
TI  - Colon adenocarcinoma multidrug resistance reverted by Euphorbia diterpenes:
      structure-activity relationships and pharmacophore modeling.
AB  - Multidrug resistance (MDR) is a limiting step on the success of cancer
      chemotherapy. The drug efflux mediated by P-gp (Pglycoprotein) is one of the best
      studied mechanisms of MDR. This paper focuses on the inhibitory P-gp efflux
      activity, pharmacophore modeling and structure-activity relationships studies of
      sixteen macrocyclic diterpenes and polycyclic derivatives obtained from Euphorbia
      species. The MDR human colon adenocarcinoma cells (COLO 320 MDR) overexpressing P
      gp were used as the biological model to screen for P-gp dependent efflux
      inhibitors. Most of the compounds showed potential as MDR reversal agents.
      Combined analysis of two different statistic algorithms, K-means clustering and
      Principal Component Analysis discriminated two clusters and showed a strong
      correlation between log P and MDR reversal activity for compounds 1-5. The most
      effective compounds (1-4 and 11-12) were tested in combination with doxorubicin
      and all potentiated its activity lowering the ID50. Pharmacophore modeling
      allowed the definition of an aromatic moiety as an additional feature to a
      previous published P-gp pharmacophore, creating a new five-point pharmacophore
      with enhanced selectivity for the most active compounds of the present study.
      Docking results also show the importance of an aromatic moiety, positively
      identifying the most relevant residues that can be linked to an inhibitory
      activity increase.

PMID- 22583417
TI  - CCR5 as a potential target in cancer therapy: inhibition or stimulation?
AB  - Extensive evidence implicates CCR5 and its ligands in the biology of tumors,
      although there is considerable controversy regarding the role of this chemokine
      receptor in cancer progression. The discrepancies between the pro- and anti-tumor
      effects of CCR5 might derive from its expression by cell types with opposing
      functions in tumor progression and the context in which tumors originate. We
      propose that CCR5 is necessary for optimal activation of the adaptive immune
      response to tumors, and for the success of certain immunotherapeutic strategies.
      Since efficient activation of T cell responses has broad implications in the
      success of some chemoand radiotherapy protocols, activation of CCR5, rather than
      its inhibition, might provide new therapeutic opportunities for cancer treatment.

PMID- 22583418
TI  - Targeted therapy for advanced urothelial cancer of the bladder: where do we
      stand?
AB  - The treatment of advanced urothelial cancer of the bladder has evolved
      substantially during recent years. Chemotherapy has been the mainstay of
      treatment and confers survival advantage. Despite such advances, the chemotherapy
      of bladder cancer is far from satisfactory due to severe side effects. Targeted
      therapy with novel drugs directed at specific molecular pathways opens promising
      new avenues to improve patient outcome. A systematic review examined the clinical
      data for novel targeted agents in 10 phase II trials, with a focus on
      bevacizumab, aflibercept, sunitinib, sorafenib, gefitinib, lapatinib and
      trastuzumab. Besides, we present studies on other novel, promising targeted
      agents, including pazopanib, cetuximab and everolimus. Although bevacizumab and
      trastuzumab have shown promising results for patients with advanced bladder
      cancer, other targeted agents have not achieved the same clinical benefit in this
      disease as seen in other common epithelial cancers. Ultimately, combination
      targeted therapy, sequential therapy, adjuvant and neoadjuvant therapy may yield
      the best outcomes.

PMID- 22583419
TI  - Experimental and theoretical advances in functional understanding of flavonoids
      as anti-tumor agents.
AB  - The potential of flavonoids to act as anti-tumor agents has been recognized but
      not fully understood because flavonoids are acting at several stages in cancer
      progression with distinct structure-function relationships. A whole family of
      structurally different flavonoids is herein described by reviewing some critical
      aspects of their pro-oxidant behavior in vitro/vivo and in cell systems by which
      they may work as antioxidants. Different classes of flavonoids (chalcones,
      flavones, isoflavones, flavanols, flavanones and anthocyanins) are synthetically
      mimicked using natural product structure-antioxidant activity relationships that
      are relevant for their enhanced function against cancer as well as severe
      inflammation conditions under which an increased oxidative stress is often
      implicated. In the context of the common mechanisms of flavonoid action, clinical
      data on benefits of flavonoids in fighting against cancer are discussed. A
      structural basis needed to improve antioxidant activity of these agents is
      elaborated in more detail.

PMID- 22583420
TI  - Platinum compounds: a hope for future cancer chemotherapy.
AB  - The discovery of cis-platin and its second and third generation analogues created
      a hope in cancer chemotherapy. Cis-platin and its second generation analogue
      carboplatin have been used for the treatment of some cancers from a long time.
      The third generation analogues have superior anti-cancer profiles for curing a
      few cancers. Unfortunately, certain side effects such as renal impairment,
      neurotoxicity and ototoxicity etc. are associated with these drugs. But,
      combination therapy makes these analogues more effective with fewer side effects.
      In addition, the results of some ongoing clinical trials will make the safety
      profile clear in near future. The present article describes the current status of
      cis-platin and its analogues in cancer chemotherapy. In addition, special
      emphasis has been made on cis-platin discovery, development of second
      (carboplatin, oxaliplatin, nedaplatin) and third (lobaplatin, heptalatin)
      generation analogues, comparison of their chemotherapies, mechanism of action,
      therapeutic status, recent developments and chronology. Moreover, attempts have
      been made to describe the future perspectives of these drugs in the cancer
      treatment.

PMID- 22583421
TI  - Treatment directed to signalling molecules in patients with advanced
      differentiated thyroid cancer.
AB  - Mutation detection in samples from thyroid cancer with the addition of BRAF
      mutation, and also the detection of RAS, RET/PTC, and PAX8/PPARgamma mutations,
      may also contribute to cancer diagnosis. On the other hand, the MAPK/ERK (mitogen
      activated protein kinase/extracellular signal-regulated kinase signaling pathway)
      and PI3K/Akt (lipid kinase phoshoinositid-3-kinase signaling pathway) play an
      important role in the transmission of cell signals. The genes, coding the
      signaling cascade proteins (RET, RAS, BRAF, PI3K, PTEN, AKT), are mutated or
      aberrantly expressed in thyroid cancer derived from follicular thyroid cells.
      Genetic and epigenetic alternations, concerning MAPK/ERK and PI3K/Akt signaling
      pathways, contribute to their activation and interaction as a consequence of
      malignant follicular cell transformation. The understanding of this molecular
      mechanism provides access to novel molecular prognostic and therapeutic
      strategies for inhibiting the oncogenic activity of the signaling pathways. This
      ability to investigate tumour biology allows for the selection of different
      drugs. Nowadays the most relevant are treatments directed to tyrosine kinase
      receptors that bind for a wide variety of ligands and are frequently mutated and
      induce a constitutive activation such that a chimerical protein expression takes
      place in follicular cells in the domain of RET, as well as in other receptors.
      Many molecules such as: motesanib, sorafenib, vandetanib, sunitinib, XL-184,
      imatinib, axitinib, pazopanib, lenvatinib, combretastatin, gefitinib, cetuximab,
      bortezomib and thiazoldonedione have been developed. Some of them also can act in
      receptors of vascular endothelial growth factor and epidermal growth factor
      receptors. Information obtained through cytological or biopsy samples permits the
      study of complex metabolic or genetic pathways, thus providing researchers with a
      high throughput tool for elucidating changes in the global expression patterns
      seen in tumour cells and allowing for different therapeutic strategies in thyroid
      cancer which take into account the predominant altered pathways observed in these
      samples.

PMID- 22583422
TI  - Rational drug design for identifying novel multi-target inhibitors for
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the hard-treating and high mortality
      cancers for which novel therapies are very much in need. Sorafenib is the first
      medication that is now approved for the treatment of patients with advanced HCC
      [1]. Sorafenib is a multikinase inhibitor targeting the Raf serine/ threonine
      kinases and the VEGFR1-3, PDGFR-b, c-Kit, Flt3 and p38 tyrosine kinases [1].
      Here, an in silico approach was directed to identify novel multi-kinase
      inhibitors as potential candidate therapies for HCC. The Molecular Operating
      Environment (MOE) was used for docking studies, pharmacophore building and
      virtual screening of chemical molecules databases. The docking/scoring methods of
      MOE were validated by reproducing the docking interactions and poses of Sorafenib
      with smallest root mean square deviations. The three receptors for which multi
      targeting compounds were screened for were: B-Raf, p38 and VEGFR-2 tyrosine
      kinases. After identifying the main binding sites of the target receptors, we
      started our studies by the docking of Sorafenib in comparison to tyrosine kinase
      inhibitors collected from the literature. A pharmacophore based on the SAR of
      Sorafenib was built using flexible alignment methods. Next, pharmacophore based
      virtual screening on four chemical molecules databases; Open NCI Database [2],
      Zinc [3], Maybridge [4] and drug bank [5] was done resulting in 2928 hit
      compounds that were subsequently subjected to filtration according to their
      binding free energies, interactions exhibited with the receptors, in silico ADMET
      properties and Lipinski's rule of five for molecule drugability [6]. Finally 7
      compounds were selected as they exhibited excellent binding interactions with the
      receptors in addition to their high safety profile that are recommended for
      further development.

PMID- 22583424
TI  - JAK2 inhibitors for myelofibrosis: why are they effective in patients with and
      without JAK2V617F mutation?
AB  - An activating mutation (V617F) in the pseudokinase domain of the Janus kinase
      (JAK)-2 tyrosine kinase has been described in 90% of patients with polycythemia
      vera (PV) and 50% of patients with essential thrombocythemia (ET) and primary
      myelofibrosis (MF). The discovery of JAK2V617F stirred the development of JAK2
      inhibitors for treatment of patients with MF, ET and PV. Similar to other
      tyrosine kinase (TK) inhibitors in current use, JAK2 inhibitors target the
      adenosine triphosphate (ATP) binding site at the TK domain and not the
      pseudokinase domain, thus affecting both mutated and wild-type kinases. In fact,
      clinical trials of these compounds have demonstrated improvements in
      constitutional symptoms and splenomegaly in patients with both mutated and wild
      type JAK2 MF. It is believed that these drugs may act not only through inhibition
      of neoplastic cell proliferation, but also by downregulating signaling through
      proinflammatory cytokine receptors. In this article, we review the current state
      of JAK2 inhibitors and discuss why these drugs could be a valuable addition to
      the treatment armamentarium for patients with and without the JAK2V617F mutation.

PMID- 22583425
TI  - Anti-cancer effects of curcumin on head and neck cancers.
AB  - Head and neck cancer is the sixth large type of cancer in the world. The
      treatment regimens for head and neck cancer encompass surgery, radiotherapy and
      chemotherapy. However, all current treatment regimens for head and neck cancer
      have adverse effects. Therefore, continuing investigations have been undertaken
      to seek less toxic therapies to reduce treatment morbidity for head and neck
      cancer. Substantial evidence has demonstrated that curcumin inhibited
      proliferation, migration, invasion and metastasis and induced apoptosis via
      modulating multiple signaling pathways in head and neck cancer. Curcumin also
      suppressed the growth of xenograft derived from head and neck cancer in vivo in
      animal models. This review summarizes the evidence demonstrating potential use of
      curcumin as a single chemotherapeutic agent or in combination with other
      chemotherapeutic agents and radiation to minimize their toxicity in head and neck
      cancer. Although curcumin has been shown to be safe at doses of 8 g/d in both
      phase I and phase II clinical trials, its bioavailability is poor. Overcoming the
      poor bioavailability of curcumin in the near future would facilitate its clinical
      use.

PMID- 22583426
TI  - Cytoskeletal alterations that confer resistance to anti-tubulin
      chemotherapeutics.
AB  - Drugs that target microtubules are a successful class of anti-cancer agents that
      have been in clinical use for over two decades. Acquired resistance to these
      drugs, however, remains a serious problem. Microtubule alterations, such as
      tubulin mutations and altered beta- tubulin isotype expression, are prominent
      factors in development of resistance. Changes in actin and intermediate filament
      proteins can also mediate sensitivity to microtubule-targeting drugs. This review
      focuses on the mechanisms by which alterations in cytoskeletal proteins lead to
      drug resistance. This information will be helpful for improving the targeting of
      microtubule toxins.

PMID- 22583427
TI  - Anticancer activity of new haloalkyl camptothecin esters against human cancer
      cell lines and human tumor xenografts grown in nude mice.
AB  - All chemotherapeutic agents currently in use have a narrow window of therapeutic
      index of 1 to 1.2. Camptothecin ester compounds are reported to have a wider
      therapeutic index when being used to treat human xenografts in nude mice. As a
      continuous effort in searching for better chemotherapeutic agents for treating
      cancers, new haloalkyl camptothecin and 9-nitrocamptothecin ester derivatives 2a
      b and 3a-d were prepared by respective acylation of camptothecin 1a and 9
      nitrocamptothecin 1b with the corresponding acylating agents. These new
      derivatives were tested in vitro against 8 human cancer cell lines using 7
      different concentrations ranging from 5 to 300 nM and also in vivo against
      various types of human tumor xenografts grown in nude mice. Most of these new
      compounds started showing inhibitory effects on the growth of 8 cancer cell lines
      at concentration of 80 nM and achieved greater than 70% inhibitions against these
      cell lines when the concentration increased to 300 nM. Compound 2a and 3a showed
      good activity against human tumor xenografts in nude mice. Compared to mother
      compound camptothecin, 3a was much less toxic in mice with a better therapeutic
      index, having the potential to be further developed as a safer treatment for
      cancers.

PMID- 22583428
TI  - Current status of tyrosine hydroxylase in management of Parkinson's disease.
AB  - Tyrosine hydroxylase (TH) is the rate limiting enzyme responsible for converting
      tyrosine to L-DOPA in the dopamine synthesis pathway. The pathophysiology of
      Parkinson's disease (PD) is largely due to the nigrostriatal dopaminergic system,
      with a decrease in TH activity, TH synthesis and TH mRNA in the striatum of PD
      and animal experimental models. TH is thus one of the main targets for gene
      therapy in PD. TH activity variations during L-DOPA and new antiparkinsonian
      treatments have been extensively studied. Pharmacological trials with
      neuroprotective treatments could modify these variations, suggesting a direct
      involvement of TH cells in the neurodegenerative process. alpha- Synuclein, the
      main component of Lewy bodies regulates the production of dopamine through its
      interaction with TH. Over-expression of alpha-synuclein reduces the levels of TH
      mRNA and protein in the brain and in this way links the histological description
      of PD and its pathological biochemistry.

PMID- 22583429
TI  - Molecular docking study of catecholamines and [4-(propan-2-yl) phenyl]carbamic
      acid with tyrosine hydroxylase.
AB  - Parkinson's disease is a major age-related neurodegenerative disorder. As the
      classical disease-related motor symptoms are associated with the loss of dopamine
      generating cells within the substantia nigra, tyrosine hydroxylase (TH), the rate
      limiting enzyme in the synthesis of catecholamines has become an important target
      in the development of Parkinson's disease drug candidates, with the focus to
      augment TH levels or its activity. By contrast, TH inhibitors are of relevance in
      the treatment of conditions associated with catecholamine over-production, as
      occurs in pheochromocytomas. To aid characterizing new drug candidates, a
      molecular docking study of catecholamines and a novel hypothetical compound [4
      (propan-2-yl) phenyl]carbamic acid (PPCA) with TH is described. Docking was
      performed using Autodock4.2 and results were analyzed using Chimera1.5.2. All the
      studied ligands were found to bind within a deep narrow groove lined with polar
      aromatic and acidic residues within TH. Our results corroborated a 'hexa
      interacting amino acids unit' located in this deep narrow groove crucial to the
      interaction of PPCA and the studied catecholamines with TH, whereby the 'His361
      His336 dyad' was found to be even more crucial to these binding interactions.
      PPCA displayed a binding interaction with human TH that was comparable to the
      original TH substrate, L-tyrosine. Hence PPCA may warrant in vitro and in vivo
      characterization with TH to assess its potential as a candidate therapeutic.

PMID- 22583430
TI  - A brief overview of tyrosine hydroxylase and alpha-synuclein in the Parkinsonian
      brain.
AB  - Parkinson's disease (PD) is associated with neurodegeneration of the
      nigrostriatal tract and is accompanied with loss of tyrosine hydroxylase (TH) and
      dopamine (DA). Development of neuroprotective strategies targeting PD is often
      undermined by lack of proper understanding of processes contributing to the
      pathology. In this mini review we have tried to briefly outline the involvement
      of TH and alpha-synuclein in PD. Aberrant expression of alpha-synuclein is toxic
      to dopaminergic neurons. It interacts with ubiquitin-proteasomal processing
      system, implicated in oxidative injury and mitochondrial dysfunction which
      ultimately induce neurodegenration and cell death. The contributions of DJ-1 in
      TH regulation have also been discussed. Brain specific TH expression with the
      combined use of the pegylated immunoliposome (PILs) gene transfer technology and
      brain specific promoters as a new approach to treat PD has also been included.

PMID- 22583433
TI  - Pathology of multiple sclerosis.
AB  - Pathological examination of the affected human tissue is key to understanding the
      possible mechanisms operating in the disease. In multiple sclerosis (MS), studies
      of central nervous system (CNS) tissues reveal the inflammatory nature of the
      disease associated with demyelination and axonal damage. Based on the concept of
      a pathogenic adaptive immune response, immunosuppressive therapies have been
      developed in an attempt to block or inhibit the potentially pathogenic T and B
      cells. More recently, re-examination of the neuropathology has led to a
      resurgence of interest in the neurodegenerative aspects of the disease, the
      involvement of cortical damage as well as the role of innate immunity in MS.
      These ideas have led to paradigm shifts from MS being the result of autoimmunity
      to myelin due to initial adaptive immune responses, to that of a
      neurodegenerative disease in which, besides T and B cells, innate immunity may
      play a major role in the disease process. The neuropathological studies have
      undoubtedly influenced pharmaceutical interest in development of neuroprotective
      approaches. Here we review the latest findings from pathological studies of MS
      tissues and discuss the relevance of these findings for future therapeutic
      approaches.

PMID- 22583431
TI  - Alzheimer's disease and type 2 diabetes: exploring the association to obesity and
      tyrosine hydroxylase.
AB  - Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are two debilitating
      health disorders afflicting millions worldwide. Recent research has revealed
      similarities between AD and T2DM. Both these protein conformational disorders are
      associated with obesity, insulin resistance, inflammation and endoplasmic
      reticulum stress, en-route initiation and/or stage aggravation. In this mini
      review we have tried to summarize studies describing obesity, insulin resistance
      and glucocorticoid imbalance as common patho-mechanisms in T2DM and AD. A
      reduction in tyrosine hydroxylase (TH) in the brain has been found to occur in
      Parkinson's disease (PD). AD, T2DM and PD share common risk factors like
      depression. Thus, whether TH is involved in the 'state of cognitive depression'
      that is the hallmark of AD and often accompanies PD and T2DM is also explored.

PMID- 22583432
TI  - Tyrosine hydroxylase gene: another piece of the genetic puzzle of Parkinson's
      disease.
AB  - The tyrosine hydroxylase (TH) gene encodes a monoxygenase that catalyzes the rate
      limiting step in dopamine biosynthesis. A hallmark of Parkinson's disease (PD) is
      the loss of dopaminergic neurons in the substantia nigra. Consistent with the
      essential role of TH in dopamine homeostasis, missense mutations in both alleles
      of TH have been associated with severe Parkinsonism-related phenotypes including
      infantile Parkinsonism. It has been speculated for a long time that genetic
      variants in the TH gene modify adult-onset PD susceptibility but the answer has
      not been clear. Genetic variants (both sequence variations and structural
      variations) can be classified into three categories based on their relative
      frequency in population: common variants (polymorphisms), rare variants and
      mutations. Each of these factors has a different mode in influencing the genetic
      risk and often requires different approaches to decipher their contributions to
      the disease. In the past few years, the revolutionary advances in genomic
      technology have allowed systematic evaluations of these genetic variants in PD,
      such as the genome-wide association study (GWAS, to survey common variants), copy
      number variation analysis (to detect structural variations), and massive parallel
      next generation sequencing (to detect rare variants and mutations). In this
      review, we have summarized the latest evidence on TH genetic variants in PD,
      including our ongoing effort of using whole exome sequencing to search for rare
      variants in PD patients.

PMID- 22583434
TI  - Recent gains in clinical multiple sclerosis research.
AB  - Multiple sclerosis (MS) is a common neurological disease mainly affecting young
      people. Around the world, over 2.5 million people suffer from this central
      nervous system (CNS) disorder. Although the exact disease mechanism is not
      completely clear, it is known that both environmental and genetic factors
      influence the development of MS. Here we aim to summarize a few major highlights
      of recent progress that have been made in clinical MS research. A genetic
      predisposition in combination with Epstein-Barr virus infection seems to be
      essential to get MS. Recently more than 50 susceptibility genetic loci for MS
      have been described. MS prevalence has a latitudinal gradient indicating that
      sunlight exposure and therefore vitamin D are important contributors to MS risk.
      Several studies found an inverse association between MS prevalence and serum
      vitamin D levels. In most cases, MS starts with an acute episode involving one or
      more sites of the CNS. The role of the recently revised McDonald Diagnostic
      Criteria for the diagnosis of MS, which sometimes allow the diagnosis after a
      first attack, is discussed. Most patients with MS suffer from exacerbations and
      remissions of neurological deficits: relapsing-and remitting MS. With time, the
      majority of these patients enter a disease phase characterized by continuous,
      irreversible neurological decline; this is called secondary progressive MS. In 10
      20% of patients, the disease is progressive from onset. Life expectancy of
      patients after diagnosis with MS is around 35 years, and MS patients die 5-10
      years earlier than the general population. A substantial percentage of MS
      patients have their first attack during childhood. Clinics of childhood-onset MS
      versus adult-onset are explained, as are diagnostics, differential diagnoses and
      therapeutic options for children with MS. Also another demyelinating disease of
      the CNS, neuromyelitis optica (NMO) is highlighted. Since NMO has been considered
      as a variant of MS and also has been misdiagnosed as MS, recent insights in the
      pathology of NMO are explained.

PMID- 22583437
TI  - Optical coherence tomography detection of neurodegeneration in multiple
      sclerosis.
AB  - The pathophysiology of multiple sclerosis (MS) is typically characterised by
      inflammation and demyelination leading to neurodegeneration, which is associated
      with disability and the progressive stages of MS. The visual system is a valuable
      tool for studying neurodegeneration and potential neuroprotection in the central
      nervous system due to its ease of accessibility. Optical coherence tomography
      (OCT) is a non-invasive tool, which can be used to measure the thickness of the
      retinal nerve fibre layer (RNFL). The thickness of RNFL is reduced following the
      development of MS and optic neuritis and can therefore be used as a correlate of
      global axonal loss. OCT is currently being investigated as a structural outcome
      measure for neuroprotective clinical trials of MS. This review describes the
      relationship between MS and optic neuritis and the associated RNFL thinning, the
      technology and advancements of OCT, the role of OCT in clinical trials for new
      neuroprotective therapies in MS and the future role of OCT in MS research.

PMID- 22583436
TI  - Endogeneous remyelination: findings in human studies.
AB  - In multiple sclerosis, conduction block in demyelinated axons underlies early
      neurological symptoms, whereas axonal transection is believed to be responsible
      for more permanent later deficits. Approved treatments for the disease are
      immunoregulatory and reduce the rate of lesion formation and clinical
      exacerbation, but are only partially effective in preventing the onset of
      disability. Remyelination is a term for the re-generation of the nerve's myelin
      sheath and is a subject of active medical research. Remyelination capacity varies
      from patient to patient or even from lesion to lesion in one and the same
      patient. Efforts to understand the causes for remyelination failure have prompted
      research into the biology of remyelination and the complex molecular factors that
      regulate remyelination. In the current review article we address challenges of
      remyelination research with a special focus on histo-pathological studies using
      brain biopsy and autopsy material. We summarize our current knowledge about
      extent of remyelination in multiple sclerosis patients and its relation to
      disease duration, lesion type, inflammation, affected brain region and gender.
      Furthermore we will address which step(s) of the oligodendrocyte maturation
      program is impaired and, thus, could be a feasible target for therapeutic
      interventions. Specifically mentioned will be the distribution of oligodendrocyte
      progenitor cells in demyelinated multiple sclerosis plaques and therapeutic
      approaches which aim to boost intrinsic properties of progenitor cells or to
      supply progenitors by cell transplantation approaches. This comprehensive
      overview is complemented by recent findings suggesting that U.S. Food and Drug
      Administration-approved treatment options, such as FTY720 (Gilenya(r)) or
      glatiramer acetate (Copaxone(r)) might boost myelin repair.

PMID- 22583435
TI  - Viruses and multiple sclerosis.
AB  - Multiple sclerosis (MS) is a heterogeneous disease that develops as an interplay
      between the immune system and environmental stimuli in genetically susceptible
      individuals. There is increasing evidence that viruses may play a role in MS
      pathogenesis acting as these environmental triggers. However, it is not known if
      any single virus is causal, or rather several viruses can act as triggers in
      disease development. Here, we review the association of different viruses to MS
      with an emphasis on two herpesviruses, Epstein-Barr virus (EBV) and human
      herpesvirus 6 (HHV-6). These two agents have generated the most impact during
      recent years as possible co-factors in MS disease development. The strongest
      argument for association of EBV with MS comes from the link between symptomatic
      infectious mononucleosis and MS and from seroepidemiological studies. In contrast
      to EBV, HHV-6 has been found significantly more often in MS plaques than in MS
      normal appearing white matter or non-MS brains and HHV-6 re-activation has been
      reported during MS clinical relapses. In this review we also suggest new
      strategies, including the development of new infectious animal models of MS and
      antiviral MS clinical trials, to elucidate roles of different viruses in the
      pathogenesis of this disease. Furthermore, we introduce the idea of using
      unbiased sequence-independent pathogen discovery methodologies, such as next
      generation sequencing, to study MS brain tissue or body fluids for detection of
      known viral sequences or potential novel viral agents.

PMID- 22583438
TI  - Clonal expansion of mitochondrial DNA deletions and the progression of multiple
      sclerosis.
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous
      system (CNS). Mechanisms of disease progression in MS are poorly understood but
      are thought to relate to both focal pathology as well as diffuse inflammation in
      the white and grey matter. Evidence points to neurodegeneration combined with a
      loss of cellular function in the remaining tissue as an important factor to the
      progression of MS. Mitochondria are implicated to play a role in the pathogenesis
      of MS with evidence of loss of mitochondrial respiratory chain activity, down
      regulation of both nuclear DNA and mitochondrial DNA (mtDNA) encoded transcripts
      as well as oxidative damage to, and deletions of, the mitochondrial DNA (mtDNA).
      The double stranded circle of mtDNA (16.6 kb) encompasses genes encoding key
      subunits within the mitochondrial respiratory chain required for the production
      of ATP as well as transfer RNA and ribosomal RNA molecules within the cell. The
      stability of mtDNA is essential for a healthy CNS as highlighted by the patients
      with primary mitochondrial disease. In this review, we focus on the potential
      role of mtDNA mutations, in particular somatic mtDNA deletions, in the
      pathogenesis of the progressive stage of MS. We propose clonal expansion of
      somatic mtDNA deletions as a potential molecular link between early inflammatory
      events and a delayed cellular energy failure, dysfunction and degeneration. The
      high level of somatic mtDNA deletions within single cells in MS is likely to
      cause cellular dysfunction as well as increase the susceptibility of the CNS
      tissue to additional stress.

PMID- 22583439
TI  - Disease modifying drugs in multiple sclerosis: mechanisms of action and new drugs
      in the horizon.
AB  - The term "disease modifying drugs" (DMD) is taken from rheumatologists who coined
      it after the use of immunosuppressive drugs and, more recently, the association
      of "biological drugs" that changed the degenerative course of rheumatic disease.
      In the treatment of multiple sclerosis (MS), the advent of interferon (IFN)-beta,
      which caused a reduction in the number of relapses and possibly improvement in
      disability outcomes, was the first strategy to prevent inflammatory damage in the
      central nervous system (CNS). Soon after, glatiramer acetate showed similar
      results. It would be more than a decade before natalizumab was licensed, showing
      a much better efficiency in relapse reduction than was seen after first-line
      therapies failed. The pipeline is now much larger with several drugs on the
      horizon. Overall, the anti-inflammatory strategy has been mostly successful but
      drugs that have protection and repair mechanisms are still missing.

PMID- 22583440
TI  - Mechanisms in the development of multiple sclerosis lesions: reconciling
      autoimmune and neurodegenerative factors.
AB  - Both immune-mediated and neurodegenerative processes play a role in the
      pathogenesis of multiple sclerosis (MS). There is still considerable debate,
      however, on how to link these two seemingly unrelated elements in disease. It has
      also remained unclear how the immune system can be involved without harboring any
      obvious myelin-directed abnormality in MS patients. Here, we propose that the
      unique properties of a small heat shock protein, HSPB5, can help reconcile the
      role of the immune system with the neurodegenerative element in MS, and explain
      the absence of any peripheral immune abnormality in patients. By being
      selectively induced as a protective stress protein in oligodendrocytes, and
      subsequently triggering activation of nearby microglia, HSPB5 accumulation
      translates neurodegenerative signals into a local innate immune response. The
      immune-regulatory profile of HSPB5-activated microglia, as well as animal model
      data, indicate that the HSPB5-induced innate response is neuroprotective.
      However, the presence of pro-inflammatory HSPB5-reactive memory T cells in the
      human immune repertoire, a unique feature among mammals, can subvert this
      response. Recruited by the innate response, such T cells respond to the
      accumulation of HSPB5 by an adaptive immune response, dominated by IFN-gamma
      production, that ultimately overwhelms the originally protective microglial
      response, and culminates in tissue damage. Thus, HSPB5 accumulation caused by
      neurodegeneration can provoke a destructive local adaptive response of an
      otherwise normal immune system. This scenario is fully consistent with known
      causative factors and the pathology of MS, and with the effects of various
      therapies. It also helps explain why MS develops only in humans.

PMID- 22583441
TI  - Potential control of multiple sclerosis by cannabis and the endocannabinoid
      system.
AB  - For many years, multiple sclerosis (MS) patients have been self-medicating with
      illegal street cannabis to alleviate symptoms associated with MS. Data from
      animal models of MS and clinical studies have supported the anecdotal data that
      cannabis can improve symptoms such as limb spasticity, which are commonly
      associated with progressive MS, by the modulation of excessive neuronal
      signalling. This has lead to cannabis-based medicines being approved for the
      treatment of pain and spasticity in MS for the first time. Experimental studies
      into the biology of the endocannabinoid system have revealed that cannabinoids
      have activity, not only in symptom relief but also potentially in neuroprotective
      strategies which may slow disease progression and thus delay the onset of
      symptoms such as spasticity. This review appraises the current knowledge of
      cannabinoid biology particularly as it pertains to MS and outlines potential
      future therapeutic strategies for the treatment of disease progression in MS.

PMID- 22583442
TI  - Multiple sclerosis: risk factors and their interactions.
AB  - Multiple sclerosis (MS) is a highly debilitating immune mediated disorder of the
      central nervous system and represents a substantial burden to the developed
      world. Despite the recent advances in MS research, which risk factors are
      implicated and how they contribute to MS pathogenesis is largely unknown.
      However, in line with older studies investigating the genetic and geographical
      epidemiology of this complex disease, more recent studies have highlighted how MS
      arises from a combination of genetic susceptibility and environmental exposures
      acting from gestation to early adulthood. Vitamin D deficiency, season of birth,
      Epstein Barr virus infection, and smoking behaviour are strongly implicated and
      able to influence genetic predisposition to MS. Furthermore, these factors appear
      to act synergistically and the risk of MS in individuals exposed to more than one
      factor combines multiplicatively. Current evidence suggests that a large part of
      MS could be prevented and understanding how and when during life risk factors act
      will ultimately aid the development of prevention strategies.

PMID- 22583443
TI  - In vitro and in vivo models of multiple sclerosis.
AB  - Multiple sclerosis (MS) is widely considered to be the result of an aggressive
      autoreactive T cell attack on myelin. How these autoimmune responses arise in MS
      is unclear, but they could result from virus infections. Thus, viral and
      autoimmune diseases in animals have been used to investigate the possible
      pathogenic mechanisms operating in MS. The autoimmune model, experimental
      autoimmune encephalomyelitis, is the most widely-used animal model and has
      greatly influenced therapeutic approaches targeting autoimmune responses. To
      investigate demyelination and remyelination in the absence of the adaptive immune
      response, toxin-induced demyelination models are used. These include using
      cuprizone, ethidium bromide and lysolecithin to induce myelin damage, which
      rapidly lead to remyelination when the toxins are withdrawn. The virus models
      include natural and experimental infections such as canine distemper, visna
      infection of sheep, and infection of non-human primates. The most commonly used
      viral models in rodents are Semliki Forest virus and Theiler's murine
      encephalomyelitis virus. The viral and experimental autoimmune encephalomyelitis
      models have been instrumental in the understanding of how viruses trigger
      inflammation, demyelination and neurodegeneration in the central nervous system.
      However, due to complexity of the animal models, pathological mechanisms are also
      examined in central nervous system cell culture systems including co-cultures,
      aggregate cultures and brain slice cultures. Here we critically review in vitro
      and in vivo models used to investigate MS. Since knowledge gained from these
      models forms the basis for the development of new therapeutic approaches for MS,
      we address the applicability of the models. Finally, we provide guidance for
      using and reporting animal studies with the aim of improving translational
      studies to the clinic.

PMID- 22583444
TI  - Multiple sclerosis - from bench to bedside.

PMID- 22583445
TI  - Commentary: research highlights (Purines, pores and pain: is it in our genes?).

PMID- 22583446
TI  - Conference report: 8th annual meeting of the society for the study of
      neuroprotection and neuroplasticity.

PMID- 22583447
TI  - Editorial: Status of tyrosine hydroxylase in the healthy and Parkinson's brain.

PMID- 22583448
TI  - Beyond the FDA PRO guidance: steps toward integrating meaningful patient-reported
      outcomes into regulatory trials and US drug labels.

PMID- 22583449
TI  - Simulated value-based insurance design applied to statin use by Medicare
      beneficiaries with diabetes.
AB  - OBJECTIVE: To examine cost responsiveness and total costs associated with a
      simulated "value-based" insurance design for statin therapy in a Medicare
      population with diabetes. METHODS: Four-year panels were constructed from the
      1997-2005 Medicare Current Beneficiary Survey selected by self-report or claims
      based diagnoses of diabetes in year 1 and use of statins in year 2 (N = 899). We
      computed the number of 30-day statin prescription fills, out-of-pocket and third
      party drug costs, and Medicare Part A and Part B spending. Multivariate ordinary
      least squares regression models predicted statin fills as a function of out-of
      pocket costs, and a generalized linear model with log link predicted Medicare
      spending as a function of number of fills, controlling for baseline
      characteristics. Estimated coefficients were used to simulate changes in fills
      associated with co-payment caps from $25 to $1 and to compute changes in third
      party payments and Medicare cost offsets associated with incremental fills.
      Analyses were stratified by patient cardiovascular event risk. RESULTS: A
      simulated out-of-pocket price of $25 [$1] increased plan drug spending by $340
      [$794] and generated Medicare Part A/B savings of $262 [$531]; savings for high
      risk patients were $558 [$1193], generating a net saving of $249 [$415].
      CONCLUSIONS: Reducing statin co-payments for Medicare beneficiaries with diabetes
      resulted in modestly increased use and reduced medical spending. The value-based
      insurance design simulation strategy met financial feasibility criteria but only
      for higher-risk patients.

PMID- 22583451
TI  - Cost-effectiveness of aldosterone antagonists for the treatment of post
      myocardial infarction heart failure.
AB  - OBJECTIVE: To assess the cost-effectiveness of eplerenone versus spironolactone
      as an adjunctive therapy to standard care in patients with heart failure (HF)
      following a myocardial infarction (post-MI) from the perspective of the National
      Health Service in the United Kingdom. METHODS: A systematic review was conducted,
      and a Bayesian meta-regression approach was used to establish the relative
      effectiveness of eplerenone and spironolactone by using evidence from randomized
      controlled trials. A decision analytic model was developed to assess the costs
      and consequences associated with the primary outcome of the trials over a
      lifetime time horizon. RESULTS: The incremental cost-effectiveness ratio of
      eplerenone compared with that of standard care alone was L 4457 and L 7893 for
      each additional quality-adjusted life-year when 2-year and lifetime treatment
      duration was assumed, respectively. In both scenarios, spironolactone did not
      appear cost-effective compared with eplerenone. The results were sensitive to the
      higher relative effectiveness estimated for eplerenone compared with
      spironolactone from the meta-regression. When a class effect was assumed for the
      effect on mortality and hospitalizations, spironolactone emerged as the most cost
      effective treatment. CONCLUSIONS: Eplerenone appears more cost-effective than
      spironolactone for the treatment of post-MI HF. These findings, however, remain
      subject to important uncertainties regarding the effects of treatment on major
      clinical events. An adequately powered, well-conducted randomized controlled
      trial that directly compares spironolactone and eplerenone may be required to
      provide more robust evidence on the optimal management of post-MI HF. Despite
      these uncertainties, the use of an aldosterone antagonist was consistently
      demonstrated to be a highly cost-effective strategy for the management of post-MI
      HF in the National Health Service.

PMID- 22583450
TI  - Exploring the relationship between Alzheimer's disease severity and longitudinal
      costs.
AB  - OBJECTIVE: The joint impact of cognitive, functional, and behavioral statuses
      must be measured when exploring the impact of new drugs on Alzheimer's disease
      (AD) costs. There are very few recent studies of AD costs by all dimensions of
      disease severity. Our objective was to improve estimation of the relationship
      between AD severity and costs of AD care by using more comprehensive AD data
      severity and a large sample size. METHODS: Participants were community-dwelling
      AD patients recruited between 2003 and 2005 and followed annually during a 2-year
      period in 50 French memory clinics. We used the Resource Use in Dementia
      questionnaire to estimate costs from a societal perspective. We explored the
      presence of potential endogeneity bias by using instrumental variable
      regressions. RESULTS: Cognitive declines impacted informal costs more than
      medical and nonmedical costs, while functional declines impacted nonmedical costs
      more than medical and informal costs. Both cognitive and function declines
      increased the total costs of care. We found that the endogeneity of these
      variables led to a large underestimation of their impact of AD severity on costs.
      CONCLUSION: Potential endogeneity should be controlled for to prevent biased
      estimations of the impact of AD severity measures on costs.

PMID- 22583452
TI  - Breast and prostate cancer productivity costs: a comparison of the human capital
      approach and the friction cost approach.
AB  - OBJECTIVES: Productivity costs constitute a substantial proportion of the total
      societal costs associated with cancer. We compared the results of applying two
      different analytical methods--the traditional human capital approach (HCA) and
      the emerging friction cost approach (FCA)--to estimate breast and prostate cancer
      productivity costs in Ireland in 2008. METHODS: Data from a survey of breast and
      prostate cancer patients were combined with population-level survival estimates
      and a national wage data set to calculate costs of temporary disability (cancer
      related work absence), permanent disability (workforce departure, reduced working
      hours), and premature mortality. RESULTS: For breast cancer, productivity costs
      per person using the HCA were ? 193,425 and those per person using the FCA were ?
      8,103; for prostate cancer, the comparable estimates were ? 109,154 and ? 8,205,
      respectively. The HCA generated higher costs for younger patients (breast cancer)
      because of greater lifetime earning potential. In contrast, the FCA resulted in
      higher productivity costs for older male patients (prostate cancer) commensurate
      with higher earning capacity over a shorter time period. Reduced working hours
      postcancer was a key driver of total HCA productivity costs. HCA costs were
      sensitive to assumptions about discount and growth rates. FCA costs were
      sensitive to assumptions about the friction period. CONCLUSIONS: The magnitude of
      the estimates obtained in this study illustrates the importance of including
      productivity costs when considering the economic impact of illness. Vastly
      different results emerge from the application of the HCA and the FCA, and this
      finding emphasizes the importance of choosing the study perspective carefully and
      being explicit about assumptions that underpin the methods.

PMID- 22583454
TI  - Reasons for rejection of patient-reported outcome label claims: a compilation
      based on a review of patient-reported outcome use among new molecular entities
      and biologic license applications, 2006-2010.
AB  - OBJECTIVES: Previous analyses of patient-reported outcome (PRO) label claims
      concentrated only on successful label claims. The goal of this research was to
      explore the reasons why PRO label claims were denied and to compile regulatory
      feedback regarding the use of PROs in clinical trials. METHODS: By using the Food
      and Drug Administration's Drug Approval Report Web page, all new molecular
      entities and biologic license applications approved between January 2006 and
      December 2010 were identified. For identified drug products, medical review
      sections from publicly available drug approval packages were reviewed to identify
      PRO end-point status and any Study Endpoints and Label Development team comments.
      RESULTS: Of the 116 new molecular entities and biologic license applications with
      accompanying drug approval packages identified and reviewed, 44.8% of the
      products included PROs as part of the pivotal studies; however, only 24.1%
      received PRO label claims. Primary reasons for denial included issues of fit for
      purpose, issues of study design, data quality or interpretation, statistical
      issues, administrative issues, and lack of demonstrated treatment benefit.
      CONCLUSIONS: Based on drug approval packages, nearly half (45%) of new molecular
      entitity/biologic license application products in the years 2006 to 2010 included
      PROs in the clinical trials supporting their approval, yet this rate is not
      reflected by claims granted. Understanding the nature of PRO claims granted under
      the current regulatory guidance is important. In addition, a clear understanding
      of denied claims yields valuable insight into where sponsors may improve
      implementation of PROs in clinical trials and submission of PRO evidence to
      increase the likelihood of obtaining PRO label claims.

PMID- 22583453
TI  - A review of patient-reported outcome labels in the United States: 2006 to 2010.
AB  - OBJECTIVE: In 2004, Willke and colleagues reviewed the efficacy endpoints
      reported in the labels of new drugs approved in the United States from 1997
      through 2002 to evaluate the use of patient-reported outcome (PRO) endpoints. Of
      the labels reviewed, 30% included PROs. Our study aimed to build on this work by
      describing the current state of PRO label claims granted for new molecular
      entities (and biologic license applications since February 2006 after the release
      of the US Food and Drug Administration (FDA) draft PRO guidance. METHODS: All new
      molecular entities and biologic license applications approved by the FDA from
      January 2006 through December 2010 were identified by using the Web page of the
      FDA Drug Approval Reports. For all identified products, drug approval packages
      and approved product labels were reviewed to identify PRO endpoint status and to
      determine the number and type of PRO claims. RESULTS: Of the 116 products
      identified, 28 (24%) were granted PRO claims; 24 (86%) were for symptoms, and, of
      these, 9 (38%) claims were pain related. Of the 28 products with PRO claims, a
      PRO was a primary endpoint for 20 (71%), all symptom related. CONCLUSIONS: The
      FDA continues to approve PRO claims, with 24% of new molecular entities and
      biologic license applications being granted. Successful PRO label claims over the
      past 5 years have generally supported treatment benefit for symptoms specified as
      primary endpoints.

PMID- 22583455
TI  - The EUROHIS-QOL 8-item index: comparative psychometric properties to its parent
      WHOQOL-BREF.
AB  - OBJECTIVES: To test the psychometric properties of the EUROHIS-QOL 8-item index,
      a shortened version of the World Health Organization Quality of Life Instrument
      Abbreviated Version (WHOQOL-BREF). METHODS: The sample consisted of 2359 subjects
      identified from primary care settings, with 1193 having a confirmed diagnosis of
      depression. Data came from six countries (Australia, Brazil, Israel, Russia,
      Spain, and the United States) involved in a large international study, the
      Longitudinal Investigation of Depression Outcomes. The structure of the EUROHIS
      QOL 8-item index follows that of the WHOQOL-BREF assessment. Internal consistency
      was measured by using Cronbach's alpha. Convergent validity was assessed by using
      correlations with different measures for mental health (Symptom Checklist 90),
      physical health (self-evaluation), and quality of life (WHOQOL-BREF and short
      form 36 health survey). Discriminant group validity was assessed between
      diagnosed depressed and nondepressed patients. Differential item functioning and
      unidimensionality were analyzed by using Rasch analysis. Factor structure was
      assessed with structural equation modeling analyses. RESULTS: Internal
      consistency was acceptable (ranged between 0.72 and 0.81 across countries), and
      the index discriminated well between depression (t = 6.31-20.33; P < 0.001)
      across all countries. Correlations between the EUROHIS-QOL 8-item index and
      different measures--Symptom Checklist 90 (r = -0.42), physical health (r = 
      0.42), WHOQOL-BREF domains (r = 0.61-0.77), and short form 36 health survey (r =
      0.58)--were all significant (P < 0.001). The index is unidimensional with desired
      item fit statistics. Two items ("daily living activities" and "enough money to
      meet your needs") had residuals exceeding 4. Differential item functioning was
      observed with general quality of life, general health, relationships, and home
      items for age. A common one-factor structure with acceptable fit was identified
      in three out of six countries (comparative fit index = 0.85, root mean square
      error of approximation = 0.11). CONCLUSIONS: The EUROHIS-QOL 8-item index showed
      acceptable cross-cultural performance and a satisfactory discriminant validity
      and would be a useful measure to include in studies to assess treatment
      effectiveness.

PMID- 22583456
TI  - Agreement between Internet-based self- and proxy-reported health care resource
      utilization and administrative health care claims.
AB  - OBJECTIVES: Although Internet-based surveys are becoming more common, little is
      known about agreement between administrative claims data and Internet-based
      survey self- and proxy-reported health care resource utilization (HCRU) data.
      This analysis evaluated the level of agreement between self- and proxy-reported
      HCRU data, as recorded through an Internet-based survey, and administrative
      claims-based HCRU data. METHODS: The Child and Household Influenza-Illness and
      Employee Function study collected self- and proxy-reported HCRU data monthly
      between November 2007 and May 2008. Data included the occurrence and number of
      visits to hospitals, emergency departments, urgent care centers, and outpatient
      offices for a respondent's and his or her household members' care. Administrative
      claims data from the MarketScan(r) Databases were assessed during the same time
      and evaluated relative to survey-based metrics. Only data for individuals with
      employer-sponsored health care coverage linkable to claims were included. The
      Kappa (kappa) statistic was used to evaluate visit concordance, and the
      intraclass correlation coefficient was used to describe frequency consistency.
      RESULTS: Agreement for presence of a health care visit and the number of visits
      were similar for self- and proxy-reported HCRU data. There was moderate to
      substantial agreement related to health care visit occurrence between survey
      based and claims-based HCRU data for inpatient, emergency department, and office
      visits (kappa: 0.47-0.77). There was less agreement on health care visit
      frequencies, with intraclass correlation coefficient values ranging from 0.14 to
      0.71. CONCLUSIONS: This study's agreement values suggest that Internet-based
      surveys are an effective method to collect self- and proxy-reported HCRU data.
      These results should increase confidence in the use of the Internet for
      evaluating disease burden.

PMID- 22583457
TI  - Comparison of 7-day recall and daily diary reports of COPD symptoms and impacts.
AB  - OBJECTIVE: Patient reporting of symptoms in a questionnaire with a 7-day recall
      period was expected to differ from symptom reporting in a 7-day symptom diary on
      the basis of cognitive theory of memory processes and several studies of symptoms
      and health behaviors. METHODS: A total of 101 adults with chronic obstructive
      pulmonary disease (COPD) completed a daily diary of items measuring symptoms and
      impacts of COPD for 7 days, and on the seventh day they completed a questionnaire
      of the same items with a 7-day recall period. The analysis examined concordance
      of 7-day recall with summary descriptors of the daily responses, examined the
      magnitude and covariates (patient characteristics and response patterns) of the
      difference between 7-day recall and mean of daily responses, and compared the
      discriminant ability and ability to detect change of 7-day recall and mean of
      daily responses. RESULTS: A 7-day recall was moderately concordant with the mean
      and maximum of daily responses and was 0.34 to 0.50 SDs higher than the mean of
      daily responses. Only the weekly report itself was a covariate of the difference.
      The discriminant ability and ability to detect change were equivalent.
      CONCLUSIONS: In measuring the weeklong experience of COPD symptoms and impacts on
      groups of patients, the 7-day recall scores were higher than the daily diary
      scores, but equivalent in detecting change over time.

PMID- 22583458
TI  - QALY weights for diabetic retinopathy--a comparison of health state valuations
      with HUI-3, EQ-5D, EQ-VAS, and TTO.
AB  - OBJECTIVE: To estimate quality-adjusted life-year weights for patients with
      diabetic retinopathy by using various methods and to investigate the empirical
      validity of the different measures. METHODS: The study population comprised 152
      patients with diabetes in Ostergotland County, Sweden. Participants were
      interviewed by telephone by using the time trade-off (TTO) method and a visual
      analogue scale (EQ-VAS) (direct valuations) as well as the EuroQol five
      dimensional questionnaire (EQ-5D) and the health utilities index mark 3 (HUI-3)
      (indirect valuations). The quality-adjusted life-year weights were adjusted for
      potential confounders by using analysis of covariance. The empirical validity of
      the measures was examined by testing their ability to detect hypothetical
      differences between severity levels of diabetic retinopathy and by investigating
      the correlation between the measures and the 25-item National Eye Institute
      Visual Function Questionnaire (NEI VFQ-25). RESULTS: All measures detected
      significant differences in scores between patient groups classified according to
      visual impairment in the better eye (analysis of covariance, P < 0.05), but only
      HUI-3 and EQ-VAS detected significant differences between patient groups
      classified according to visual impairment or pathological progression in the
      worse eye. HUI-3 recorded a difference of 0.43 in values between normal vision
      and blindness in the better eye, which was more than twice the differences
      captured by the other measures (0.15-0.20). In addition, HUI-3 showed the highest
      correlation with NEI VFQ-25 (r = 0.54; P < 0.001). CONCLUSIONS: In cost-utility
      analyses, the choice of quality-adjusted life-year measure may affect whether an
      intervention is considered cost-effective. Furthermore, if decisions are to be
      based on values from the general public, HUI-3 can be recommended for cost
      utility analyses of interventions directed at diabetic retinopathy.

PMID- 22583459
TI  - Mapping from disease-specific measures to health-state utility values in
      individuals with migraine.
AB  - OBJECTIVE: The objective of this study was to develop empirical algorithms that
      estimate health-state utility values from disease-specific quality-of-life scores
      in individuals with migraine. METHODS: Data from a cross-sectional, multicountry
      study were used. Individuals with episodic and chronic migraine were randomly
      assigned to training or validation samples. Spearman's correlation coefficients
      between paired EuroQol five-dimensional (EQ-5D) questionnaire utility values and
      both Headache Impact Test (HIT-6) scores and Migraine-Specific Quality-of-Life
      Questionnaire version 2.1 (MSQ) domain scores (role restrictive, role preventive,
      and emotional function) were examined. Regression models were constructed to
      estimate EQ-5D questionnaire utility values from the HIT-6 score or the MSQ
      domain scores. Preferred algorithms were confirmed in the validation samples.
      RESULTS: In episodic migraine, the preferred HIT-6 and MSQ algorithms explained
      22% and 25% of the variance (R(2)) in the training samples, respectively, and had
      similar prediction errors (root mean square errors of 0.30). In chronic migraine,
      the preferred HIT-6 and MSQ algorithms explained 36% and 45% of the variance in
      the training samples, respectively, and had similar prediction errors (root mean
      square errors 0.31 and 0.29). In episodic and chronic migraine, no statistically
      significant differences were observed between the mean observed and the mean
      estimated EQ-5D questionnaire utility values for the preferred HIT-6 and MSQ
      algorithms in the validation samples. CONCLUSIONS: The relationship between the
      EQ-5D questionnaire and the HIT-6 or the MSQ is adequate to use regression
      equations to estimate EQ-5D questionnaire utility values. The preferred HIT-6 and
      MSQ algorithms will be useful in estimating health-state utilities in migraine
      trials in which no preference-based measure is present.

PMID- 22583460
TI  - Mapping the Functional Assessment of Cancer Therapy-general or -Colorectal to SF
      6D in Chinese patients with colorectal neoplasm.
AB  - OBJECTIVES: To map Functional Assessment of Cancer Therapy-General (FACT-G) and
      Functional Assessment of Cancer Therapy-Colorectal (FACT-C) subscale scores onto
      six-dimensional health state short form (derived from short form 36 health
      survey) (SF-6D) preference-based values in patients with colorectal neoplasm,
      with and without adjustment for clinical and demographic characteristics. These
      results can then be applied to studies that have used FACT-G or FACT-C to predict
      SF-6D utility values to inform economic evaluation. METHODS: Ordinary least
      square regressions were estimated mapping FACT-G and FACT-C onto SF-6D by using
      cross-sectional data of 537 Chinese subjects with different stages of colorectal
      neoplasm. Mapping functions for SF-6D preference-based values were developed
      separately for FACT-G and FACT-C in four sequential models for addition of
      variables: 1) main-effect terms, 2) squared terms, 3) interaction terms, and 4)
      clinical and demographic variables. Predictive performance in each model was
      assessed by the R(2), adjusted R(2), predicted R(2), information criteria (Akaike
      information criteria and Bayesian information criteria), the root mean square
      error, the mean absolute error, and the proportions of absolute error within the
      threshold of 0.05 and 0.10. RESULTS: Models including FACT variables and clinical
      and demographic variables had the best predictive performance measured by using
      R(2) (FACT-G: 59.98%; FACT-C: 60.43%), root mean square error (FACT-G: 0.086;
      FACT-C: 0.084), and mean absolute error (FACT-G: 0.065; FACT-C: 0.065). The FACT
      C-based mapping function had better predictive ability than did the FACT-G-based
      mapping function. CONCLUSIONS: Models mapping FACT-G and FACT-C onto SF-6D
      reached an acceptable degree of precision. Mapping from the condition-specific
      measure (FACT-C) had better performance than did mapping from the general cancer
      measure (FACT-G). These mapping functions can be applied to FACT-G or FACT-C data
      sets to estimate SF-6D utility values for economic evaluation of medical
      interventions for patients with colorectal neoplasm. Further research assessing
      model performance in independent data sets and non-Chinese populations are
      encouraged.

PMID- 22583461
TI  - Condition-specific preference-based measures: benefit or burden?
AB  - OBJECTIVES: Some argue that generic preference-based measures (PBMs) are not
      sensitive to certain disease-specific improvements. To overcome this problem, new
      condition-specific PBMs (CS-PBMs) are being developed, but it is not yet clear
      how such measures compare with existing generic PBMs. METHOD: We generated CS
      PBMs from three condition-specific questionnaires (Health Assessment
      Questionnaire for arthritis, Quality of Life Questionnaire for Cancer 30 for
      cancer, and Multiple Sclerosis Impact Scale 29 for multiple sclerosis). First,
      the questionnaires were reduced in content, and then, a time trade-off study was
      conducted in the general public (N = 402) to obtain weights associated with the
      dimensions and levels of the new questionnaire. Finally, we compared utilities
      obtained by using the CS-PBMs with utilities obtained by using the EuroQol five
      dimensional (EQ-5D) questionnaire in four data sets. RESULTS: Utility values
      generated by the CS-PBMs were higher than those of the EQ-5D questionnaire. The
      Health Assessment Questionnaire-based measure for arthritis proved to be
      insensitive to comorbidities. Measures based on the Multiple Sclerosis Impact
      Scale 29 and the Quality of Life Questionnaire for Cancer 30 discriminated
      comorbidities and side effect equally well as the EQ-5D questionnaire and were
      more sensitive than the EQ-5D questionnaire for mild impairments. CONCLUSIONS:
      The introduction of PBMs that are specific to a certain disease may have the
      merit of sensitivity to disease-specific effects of interventions. That gain,
      however, is traded off to the loss of comparability of utility values and, in
      some cases, insensitivity to side effects and comorbidity. The use of a CS-PBM
      for cost-utility analysis is warranted only under strict conditions.

PMID- 22583462
TI  - Do general practitioners know patients' preferences? An empirical study on the
      agency relationship at an aggregate level using a discrete choice experiment.
AB  - OBJECTIVES: This study investigated whether general practitioners (GPs) know
      patients' preferences regarding a number of organizational characteristics in
      general practice (i.e., waiting time on the telephone, opening hours, waiting
      time to the appointment, distance to the general practice, waiting time in the
      waiting room, consultation time, and whether the GP or assisting personnel
      performs routine tasks) to examine whether there is a basis for improving the
      agency relationship at an aggregate level. DATA: A total of 698 respondents from
      the Danish population and 969 GPs answered the questionnaire in May and September
      2010. METHODS: In a discrete choice experiment, GPs and patients made both forced
      and unforced choices, allowing us to explore the congruence of preferences 1)
      when patients must choose a new GP and 2) when they can stay with their current
      GP. RESULTS: Results show that in the forced choice, preferences are seen to
      differ. In the unforced choice also, preferences differ--mainly because GPs
      overestimate their own importance to the patients. Rank orders, however, are
      similar for both GPs and patients. CONCLUSIONS: It is concluded that GPs do not
      have a precise knowledge of patients' preferences. However, in the unforced
      choice, GPs do know on which attributes to compete although they underestimate
      the necessity of competition. The overall conclusion is that there is room for
      improving the agency relationship in the organization of general practice.

PMID- 22583463
TI  - Efficacy of once-daily indacaterol relative to alternative bronchodilators in
      COPD: a patient-level mixed treatment comparison.
AB  - OBJECTIVE: Indacaterol was evaluated versus placebo, formoterol, and salmeterol
      in randomized controlled trials. No direct comparisons, however, are available
      for indacaterol 150 MUg with formoterol or indacaterol 300 MUg with salmeterol.
      Indacaterol trial evidence was synthesized to provide coherent estimates of
      indacaterol 150 MUg and indacaterol 300 MUg relative to formoterol, salmeterol,
      and tiotropium. METHODS: Four randomized controlled trials were combined with
      Bayesian mixed treatment comparisons by using individual patient-level data. End
      points of interest were trough forced expiratory volume in 1 second (FEV(1)), St.
      George's Respiratory Questionnaire (SGRQ) total score and response (>= 4 points),
      and Transition Dyspnea Index total score and response (>= 1 point). RESULTS:
      Indacaterol 150 MUg demonstrated a higher FEV(1) than did formoterol at 12 weeks
      and 6 months (0.10 L difference; 95% credible interval [CrI] = 0.06-0.14), as did
      indacaterol 300 MUg versus salmeterol (0.06 L difference at 12 weeks; CrI = 0.02
      0.10; 0.06 L at 6 months; CrI = 0.02-0.11). Regarding SGRQ, indacaterol 150 MUg
      demonstrated a comparable proportion of responders versus formoterol, as did
      indacaterol 300 MUg versus salmeterol. In comparison to tiotropium, indacaterol
      150 MUg demonstrated a greater proportion of responders (odds ratio = 1.52 at 12
      weeks; CrI 1.15-2.00). For Transition Dyspnea Index, indacaterol 150 MUg and
      formoterol showed a similar response. Indacaterol 300 MUg was more efficacious
      than salmeterol (odds ratio = 1.65 at 12 weeks; CrI 1.16-2.34). Overall,
      indacaterol 150 MUg showed the greatest efficacy for SGRQ and indacaterol 300 MUg
      for FEV(1) and Transition Dyspnea Index. CONCLUSION: Indacaterol is expected to
      be comparable to formoterol, salmeterol, and tiotropium, providing higher FEV(1)
      than formoterol and salmeterol and greater improvement in the SGRQ total score
      than tiotropium. Indacaterol 150 MUg provided comparable improvement in dyspnea,
      while indacaterol 300 MUg demonstrated the greatest response overall.

PMID- 22583464
TI  - Decision-making criteria among national policymakers in five countries: a
      discrete choice experiment eliciting relative preferences for equity and
      efficiency.
AB  - BACKGROUND: Worldwide, there is a need for formalization of the priority setting
      processes in health. Recent research has used the term multicriteria decision
      analysis for methods that systematically include preferences for both equity and
      efficiency. The present study compares decision-makers' preferences at the
      country level for a set of equity and efficiency criteria according to a
      multicriteria decision analysis framework. METHODS: Discrete choice experiments
      were conducted for Brazil, Cuba, Nepal, Norway, and Uganda. By using standardized
      methods, we elicited preferences for intervention attributes using a individual
      choice questionnaire. A multinomial logistic regression was applied to estimate
      the coefficients for all single-policy criteria, per country. Attributes were
      assigned to an equity group or to an efficiency group. After testing for scale
      variance, predicted probabilities for interventions with both types of attributes
      were compared across countries. RESULTS: The Norway and Nepal groups showed
      considerable preferences for efficiency criteria over equity criteria with
      percent change in respective predicted sum probabilities of [10%, -84%] and [6%, 
      79%]. Brazil and Uganda also showed preference for the efficiency criteria though
      less convincingly ([-34%, -93%], [-18%, -63%], respectively). The Cuban group
      showed the strongest preferences with equity attributes dominating efficiency ([
      52%, 213%]). CONCLUSIONS: Group preferences of policymakers show explicit but
      varying trade-offs of efficiency and equity in these diverse settings. This
      multicriteria decision analysis approach, using discrete choice experiments,
      indicates that systematic setting of health priorities is possible across a
      variety of countries. It may be a valuable tool to guide health reform
      initiatives.

PMID- 22583465
TI  - Handling input correlations in pharmacoeconomic models.
AB  - OBJECTIVES: Probabilistic uncertainty analysis is a common means of evaluating
      pharmacoeconomic models and exploring decision uncertainty. Uncertain parameters
      are assigned probability distributions and analyses performed by Monte Carlo
      simulation. Correlations between input parameters are rarely accounted for
      despite recommendations from several guidelines. By outlining theoretical reasons
      for including correlations and showing numerous examples of existing
      correlations, we appeal to the analyst to consider input dependencies. Our
      objective is to review the available methods to do so, give technical details on
      implementation and show, by using examples of published studies, the effect input
      correlations have on model outputs. METHODS: A hierarchy of methods for dealing
      with correlations in Monte Carlo simulation is presented and used. The choice of
      method depends on the amount of information available on dependency and consists
      of functional modeling, joint distributions/copulas, and coupling of marginal
      distributions. RESULTS: We induced input correlation with various methods and
      showed that in most cases the choice of optimal decision remained the same as in
      the independent scenario. There was, however, a significant change in the value
      of further information because of inducing input correlations. The results were
      similar for various dependency structures and were mainly a function of the
      strength of correlation, as measured by the linear correlation coefficient.
      CONCLUSION: Probabilistic uncertainty analysis reflects joint uncertainty across
      input parameters only when dependence among input parameters is accounted for.

PMID- 22583466
TI  - Tails from the peak district: adjusted limited dependent variable mixture models
      of EQ-5D questionnaire health state utility values.
AB  - OBJECTIVES: Health utility data generated by using the EuroQol five-dimensional
      (EQ-5D) questionnaire are right bounded at 1 with a substantial gap to the next
      set of observations, left bounded, and multimodal. These features present
      challenges to the estimation of the effect of clinical and socioeconomic
      characteristics on health utilities. Our objective was to develop and demonstrate
      an appropriate method for dealing with these features. METHODS: We developed a
      statistical model that incorporates an adjusted limited dependent variable
      approach to reflect the upper bound and the large gap in feasible EQ-5D
      questionnaire values. Further flexibility was then gained by adopting a mixture
      modeling framework to address the multimodality of the EQ-5D questionnaire
      distribution. We compared the performance of these approaches with that of those
      frequently adopted in the literature (linear and Tobit models) by using data from
      a clinical trial of patients with rheumatoid arthritis. RESULTS: We found that
      three latent classes are appropriate in estimating EQ-5D questionnaire values
      from function, pain, and sociodemographic factors. Superior performance of the
      adjusted limited dependent variable mixture model was achieved in terms of Akaike
      and Bayesian information criteria, root mean square error, and mean absolute
      error. Unlike other approaches, the adjusted limited dependent variable mixture
      model fits the data well at high EQ-5D questionnaire levels and cannot predict
      unfeasible EQ-5D questionnaire values. CONCLUSIONS: The distribution of the EQ-5D
      questionnaire is characterized by features that raise statistical challenges. It
      is well known that standard approaches do not perform well for this reason. This
      article developed an appropriate method to reflect these features by combining
      limited dependent variable and mixture modeling and demonstrated superior
      performance in a rheumatoid arthritis setting. Further refinement of the general
      framework and testing in other data sets are warranted. Analysis of utility data
      should apply methods that recognize the distributional features of the data.

PMID- 22583467
TI  - On discounting of health gains from human papillomavirus vaccination: effects of
      different approaches.
AB  - OBJECTIVES: Discounting has long been a matter of controversy in the field of
      health economic evaluations. How to weigh future health effects has resulted in
      ongoing discussions. These discussions are imminently relevant for health care
      interventions with current costs but future benefits. Different approaches to
      discount health effects have been proposed. In this study, we estimated the
      impact of different approaches for discounting health benefits of human
      papillomavirus (HPV) vaccination. METHODS: An HPV model was used to estimate the
      impact of different discounting approaches on the present value of health
      effects. For the constant discount approaches, we varied the discount rate for
      health effects ranging from 0% to 4%. Next, the impact of relevant alternative
      discounting approaches was estimated, including hyperbolic, proportional,
      stepwise, and time-shifted discounting. RESULTS: The present value of health
      effects gained through HPV vaccination varied strongly when varying discount
      rates and approaches. The application of the current Dutch guidelines resulted in
      a present value of health effects that was eight or two times higher than that
      produced when using the proportional discounting approach or when using the
      internationally more common 4% discount rate for health effects, respectively.
      Obviously, such differences translate into large variations in corresponding
      incremental cost-effectiveness ratios. CONCLUSION: The exact discount rate and
      approach chosen in an economic evaluation importantly impact the projected value
      of health benefits of HPV vaccination. Investigating alternative discounting
      approaches in health-economic analysis is important, especially for vaccination
      programs yielding health effects far into the future. Our study underlines the
      relevance of ongoing discussions on how and at what rates to discount.

PMID- 22583468
TI  - Reflections: NICE, health economics, and outcomes research.

PMID- 22583469
TI  - Coverage with evidence development, only in research, risk sharing, or patient
      access scheme? A framework for coverage decisions.
AB  - BACKGROUND: Until recently, purchasers' options regarding whether to pay for the
      use of medical technologies have been binary in nature: a treatment is either
      covered or not. Policies, however, have emerged that expand the decision options,
      for example, linking coverage to evidence development, an option increasingly
      used for treatments with limited/uncertain evidence. There has been little effort
      to reconcile the features of technologies with the available decision options.
      METHODS: We described a framework within which different decision options can be
      evaluated. We distinguished two sources of value in terms of health: the value of
      the technology per se and the value of reducing decision uncertainty. The costs
      of reversing decisions were also considered. FINDINGS: Purchasers should weigh
      the expected benefits of coverage against the possibility that the decision may
      need to be reversed and the chance that adoption will hinder evidence generation.
      Based on the purchaser's range of authority over access, research, and price and
      on the characteristics of the technology with regard to reversibility and
      evidence, different decisions may be appropriate. The framework clarified the
      assessments needed to establish the appropriateness of different decisions. A
      taxonomy of coverage decisions was suggested. CONCLUSIONS: A range of decision
      options may facilitate paying for the use of promising medical technologies
      despite their uncertain evidence. It is important that the option be chosen on
      the basis of not only the expected value of a technology but also the value of
      further research, the anticipated effect of coverage on further research, and the
      costs associated with reversing the decision.

PMID- 22583470
TI  - Guidelines for health technologies: specific guidance for oncology products in
      Canada.
AB  - OBJECTIVE: Specific methodological challenges are often encountered during cancer
      related economic evaluations. The objective of this study was to provide specific
      guidance to analysts on the methods for the conduct of high-quality economic
      evaluations in oncology by building on the Canadian Agency for Drugs and
      Technologies in Health Guidelines for the Economic Evaluation of Health
      Technologies (third edition). METHODS: Fifteen oncologists, health economists,
      health services researchers, and decision makers from across Canada identified
      sections in Canadian Agency for Drugs and Technologies in Health guidelines that
      would benefit from oncology-specific guidance. Fifteen sections of the guidelines
      were reviewed to determine whether 1) Canadian Agency for Drugs and Technologies
      in Health guidelines were sufficient for the conduct of oncology economic
      evaluations without further guidance specific for oncology products or 2)
      additional guidance was necessary. A scoping review was conducted by using a
      comprehensive and replicable search to identify relevant literature to inform
      recommendations. Recommendations were reviewed by representatives of academia,
      government, and the pharmaceutical industry in an iterative and formal review of
      the recommendations. RESULTS: Major adaptations for guidance related to time
      horizon, effectiveness, modeling, costs, and resources were required.
      Recommendations around the use of final outcomes over intermediate outcomes to
      calculate quality-adjusted life-years and life-years gained, the type of
      evidence, the source of evidence, and the use of time horizon and modeling were
      made. CONCLUSIONS: This article summarizes key recommendations for the conduct of
      economic evaluations in oncology and describes methods required to ensure that
      economic assessments in oncology are conducted in a standardized manner.

PMID- 22583471
TI  - Australian managed entry scheme: a new manageable process for the reimbursement
      of new medicines?
AB  - The global prescription medicines industry argues that it needs high prices for
      new medicines to meet ever-increasing development costs. While many payers are
      prepared to pay high prices if they represent good value for money, they first
      need to feel assured that the value for money estimates are robust. Insofar as
      new medicines enter the market with limited and uncertain data relating to their
      performance in normal clinical practice, the value for money case for some
      medicines may well be driven largely by assumptions than by empirical evidence.
      The concern to manufacturers is that payers respond to this uncertainty by
      listing the product at a lower price (which may not satisfy the producer) or not
      listing the product until more evidence is available (which may not satisfy
      clinicians and patients). Is there a solution that will satisfy all key
      stakeholders? Will clinicians and patients continue to have timely access to new
      medicines and will payers have sustainable reimbursement systems? Will the
      industry continue to be rewarded with high prices for new medicines so long as
      they represent good value for money? In 2011, the Australian Government
      introduced a managed entry scheme whereby the Pharmaceutical Benefits Advisory
      Committee will recommend the listing of a new medicine at a price justified by
      the existing evidence, pending the availability of more conclusive evidence of
      cost-effectiveness to support its continued listing at a higher price. This
      commentary examines the Australian Government's managed entry scheme and issues
      that are likely to arise from its implementation.

PMID- 22583473
TI  - Comment on the use of vignettes and the EQ-5D to value disease-specific health
      states.

PMID- 22583475
TI  - Catalytic asymmetric ring openings of meso and terminal aziridines with halides
      mediated by chiral 1,2,3-triazolium silicates.
AB  - Catalytic asymmetric chloride and bromide ring openings of meso aziridines with
      trimethylsilyl halides have been developed using modular chiral 1,2,3-triazolium
      chlorides as catalysts. Control experiments suggest the reaction pathway
      involving hypervalent silicate ions as reactive intermediates. The application of
      this system to the efficient kinetic resolution of terminal aziridines is also
      reported.

PMID- 22583474
TI  - Dose-specific efficacy of Haemophilus influenzae type b conjugate vaccines: a
      systematic review and meta-analysis of controlled clinical trials.
AB  - Global coverage of infant Haemophilus influenzae type b (Hib) vaccination has
      increased considerably during the past decade, partly due to GAVI Alliance
      donations of the vaccine to low-income countries. In settings where large numbers
      of children receive only one or two vaccine doses rather than the recommended
      three doses, dose-specific efficacy estimates are needed to predict impact. The
      objective of this meta-analysis is to determine Hib vaccine efficacy against
      different clinical outcomes after receiving one, two or three doses of vaccine.
      Studies were eligible for inclusion if a prospective, controlled design had been
      used to evaluate commercially available Hib conjugate vaccines. Eight studies
      were included. Pooled vaccine efficacies against invasive Hib disease after one,
      two or three doses of vaccine were 59%, 92% and 93%, respectively. The meta
      analysis provides robust estimates for use in decision-analytical models designed
      to predict the impact of Hib vaccine.

PMID- 22583476
TI  - Methylated spirit burns: an ongoing problem.
AB  - OBJECTIVE: Despite many educational campaigns we still see burns caused by
      methylated spirit every year. We undertook a retrospective study to analyse the
      impact of this problem. METHODS: We retrospectively collected data of all
      patients with burns caused by methylated spirit over twelve years from 1996 to
      2008. Our main endpoints were: incidence, age, mechanism of injury, total body
      surface area (TBSA) burned, burn depth, need for surgery and length of hospital
      stay. RESULTS: Ninety-seven patients with methylated spirit burns were included.
      During the study period there was no decrease in the number of patients annually
      admitted to the burn unit with methylated spirit burns. 28% of the patients
      (n=27) were younger than eighteen years old, 15% (n=15) were ten years old or
      younger. The most common cause of burns was carelessness in activities involving
      barbecues, campfires and fondues. Mean TBSA burned was 16% (SD 12.4). 70% (n=68)
      had full thickness burns. 66% (n=64) needed grafting. Mean length of hospital
      stay was 23 days (SD 24.7). CONCLUSIONS: The use of methylated spirit is an
      ongoing problem, which continues to cause severe burns in adults and children.
      Therefore methylated spirit should be banned in households. We suggest sale only
      in specialised shops, clear labelling and mandatory warnings.

PMID- 22583477
TI  - Association between carotid intima-media thickness, buccodental status, and
      glycemic control in pediatric type 1 diabetes.
AB  - OBJECTIVE: To evaluate the association between carotid intima-media thickness,
      buccodental status, and glycemic control in patients with type 1 diabetes.
      METHODS: Cross-sectional study with consecutive cases attended in an outpatient
      clinic (n = 69). Medical and clinical dental history, HbA1c, lipid profile,
      treatment period, and daily insulin dosage were recorded. Sociodemographic data
      and anthropometrical measurements were obtained by standardized questionnaire.
      Doppler real-time ultrasound was performed by a single experienced vascular
      radiologist blinded to the study. Assessment of buccodental status was done by
      the Maxillofacial Unit of the Pediatrics Hospital, and an oral scrape culture was
      collected. RESULTS: The mean age was 11.7 +/- 3.0 years, with diabetes 5.1 +/-
      3.3 years. Mean HbA1c was 8.5 +/- 1.7%. Primary teeth were present in 52.2% and
      bacterial plaque in 94.2%. Buccodental conditions featured caries (63.8%),
      gingivitis (84%), and enamel demineralization (26.1%): white spot lesions (18.8%)
      and cavitated lesions (7.3%). Bacteria associated with caries were found in
      44.1%. Patients in the highest HbA1c tertile (>8.5%) had greater frequency of
      buccodental conditions and were positive for Streptococcus mutans and Candida
      albicans; also, cIMT increased and vessel compliance decreased compared to those
      in the lowest tertile (<7.0%) (p < 0.05). CONCLUSIONS: More buccodental
      conditions and carotid intima-media thickness increase appeared in the patients
      with HbA1c level > 8.5%, suggesting onset of atherosclerosis. The correlation
      between buccodental status and HbA1c values may indicate the connection between
      inflammatory states of atherosclerosis and type 1 diabetes.

PMID- 22583478
TI  - Downregulation of the tumor-suppressor miR-16 via progestin-mediated oncogenic
      signaling contributes to breast cancer development.
AB  - INTRODUCTION: Experimental and clinical evidence points to a critical role of
      progesterone and the nuclear progesterone receptor (PR) in controlling mammary
      gland tumorigenesis. However, the molecular mechanisms of progesterone action in
      breast cancer still remain elusive. On the other hand, micro RNAs (miRNAs) are
      short ribonucleic acids which have also been found to play a pivotal role in
      cancer pathogenesis. The role of miRNA in progestin-induced breast cancer is
      poorly explored. In this study we explored progestin modulation of miRNA
      expression in mammary tumorigenesis. METHODS: We performed a genome-wide study to
      explore progestin-mediated regulation of miRNA expression in breast cancer. miR
      16 expression was studied by RT-qPCR in cancer cell lines with silenced PR,
      signal transducer and activator of transcription 3 (Stat3) or c-Myc, treated or
      not with progestins. Breast cancer cells were transfected with the precursor of
      miR-16 and proliferation assays, Western blots or in vivo experiments were
      performed. Target genes of miR-16 were searched through a bioinformatical
      approach, and the study was focused on cyclin E. Reporter gene assays were
      performed to confirm that cyclin E 3'UTR is a direct target of miR-16. RESULTS:
      We found that nine miRNAs were upregulated and seven were downregulated by
      progestin in mammary tumor cells. miR-16, whose function as a tumor suppressor in
      leukemia has already been shown, was identified as one of the downregulated
      miRNAs in murine and human breast cancer cells. Progestin induced a decrease in
      miR-16 levels via the classical PR and through a hierarchical interplay between
      Stat3 and the oncogenic transcription factor c-Myc. A search for miR-16 targets
      showed that the CCNE1 gene, encoding the cell cycle regulator cyclin E, contains
      conserved putative miR-16 target sites in its mRNA 3' UTR region. We found that,
      similar to the molecular mechanism underlying progestin-modulated miR-16
      expression, Stat3 and c-Myc participated in the induction of cyclin E expression
      by progestin. Moreover, overexpression of miR-16 abrogated the ability of
      progestin to induce cyclin E upregulation, revealing that cyclin E is a novel
      target of miR-16 in breast cancer. Overexpression of miR-16 also inhibited
      progestin-induced breast tumor growth in vitro and in vivo, demonstrating for the
      first time, a role for miR-16 as a tumor suppressor in mammary tumorigenesis. We
      also found that the ErbB ligand heregulin (HRG) downregulated the expression of
      miR-16, which then participates in the proliferative activity of HRG in breast
      tumor cells. CONCLUSIONS: In this study, we reveal the first progestin-regulated
      miRNA expression profile and identify a novel role for miR-16 as a tumor
      suppressor in progestin- and growth factor-induced growth in breast cancer.

PMID- 22583481
TI  - Identification of novel polo-like kinase 1 inhibitors by a hybrid virtual
      screening.
AB  - Polo-like kinase 1 is an important and attractive oncological target that plays a
      key role in mitosis and cytokinesis. A combined pharmacophore- and docking-based
      virtual screening was performed to identify novel polo-like kinase 1 inhibitors.
      A total of 34 hit compounds were selected and tested in vitro, and some compounds
      showed inhibition of polo-like kinase 1 and human tumor cell growth. The most
      potent compound (66) inhibited polo-like kinase 1 with an IC(50) value of 6.99
      MUm. The docked binding models of two hit compounds were discussed in detail.
      These compounds contained novel chemical scaffolds and may be used as foundations
      for the development of novel classes of polo-like kinase 1 inhibitors.

PMID- 22583482
TI  - A proprietary topical preparation containing EGCG-stearate and glycerin with
      inhibitory effects on herpes simplex virus: case study.
AB  - The effects of a proprietary topical formulation containing EGCG-stearate in 100%
      glycerin USP were studied in two volunteer patients with recurrent herpes simplex
      (HSV) type 1. Application during early onset (prodromal stage) in a patient with
      herpes labialis prevented lesion progression. In a second patient with herpetic
      stomatitis, application of the formula during a later stage (inflammation stage)
      led to a remarkably shortened duration of symptoms. In contrast, a third patient
      provided 100% glycerin USP only as placebo failed to demonstrate any therapeutic
      or preventive effect against lesion occurrence or duration of lesion and healing
      time. These results suggest that this proprietary topical preparation could be
      used effectively to prevent and treat HSV-induced symptoms, and warrants further
      clinical investigation.

PMID- 22583483
TI  - Non-selective inhibition of cyclooxygenase enzymes by aminoacetylenic isoindoline
      1,3-diones.
AB  - The reported pharmacological activities of acetylenic and phthalimide groups
      promoted our interest to synthesize a novel series of N-[4-(t-amino-yl)-but-2-yn
      1-yl] isoindoline-1,3-diones as anti-inflammatory compounds. The aim of this
      research is to investigate the selectivity of two compounds, ZM4 and ZM5, on
      inhibiting cyclooxygenase (COX) in vitro and in silico as well as reducing
      carrageenan-induced edema in rats. Oral administration of 5-20 mg/kg ZM4 and ZM5
      reduced significantly carrageenan-induced edema in dose-and time dependent
      manner. Furthermore, the IC50 values induced by ZM4 and ZM5 were in the range of
      3.0-3.6 MUM for COX1 and COX 2 but were higher than those induced by Diclofenac
      and Celecoxib, respectively. Docking of ZM4 and ZM5 in both COX enzymes, on the
      other hand, exhibited the conventional binding modes that are usually adopted by
      different non-steroidal anti-inflammatory drugs (NSAIDs). Furthermore, ZM4 and
      ZM5 bind to COX enzymes as strongly as Flurbiprofen and Celecoxib. In conclusion,
      aminoacetylenic isoindoline 1, 3-dione compounds have shown anti-inflammatory
      activity by inhibiting COX-1 and COX-2 enzymes. Interestingly, the best hits
      showed inhibition at low micromolar levels although they are not selective at
      this stage. Further research will be conducted to improve both selectivity and
      potency.

PMID- 22583480
TI  - The prevalence of Chlamydia trachomatis infection in Australia: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Chlamydia trachomatis is a common sexually transmitted infection in
      Australia. This report aims to measure the burden of chlamydia infection by
      systematically reviewing reports on prevalence in Australian populations.
      METHODS: Electronic databases and conference websites were searched from 1997
      2011 using the terms 'Chlamydia trachomatis' OR 'chlamydia' AND 'prevalence' OR
      'epidemiology' AND 'Australia'. Reference lists were checked and researchers
      contacted for additional literature. Studies were categorised by setting and
      participants, and meta-analysis conducted to determine pooled prevalence
      estimates for each category. RESULTS: Seventy-six studies met the inclusion
      criteria for the review. There was a high level of heterogeneity between studies;
      however, there was a trend towards higher chlamydia prevalence in younger
      populations, Indigenous Australians, and those attending sexual health centres.
      In community or general practice settings, pooled prevalence for women <25 years
      in studies conducted post-2005 was 5.0% (95% CI: 3.1, 6.9; five studies), and for
      men <30 years over the entire review period was 3.9% (95% CI: 2.7, 5.1; six
      studies). For young Australians aged <25 years attending sexual health, family
      planning or youth clinics, estimated prevalence was 6.2% (95% CI: 5.1, 7.4; 10
      studies) for women and 10.2% (95% CI: 9.5, 10.9; five studies) for men. Other key
      findings include pooled prevalence estimates of 22.1% (95% CI: 19.0, 25.3; three
      studies) for Indigenous women <25 years, 14.6% (95% CI: 11.5, 17.8; three
      studies) for Indigenous men <25 years, and 5.6% (95% CI: 4.8, 6.3; 11 studies)
      for rectal infection in men who have sex with men. Several studies failed to
      report basic demographic details such as sex and age, and were therefore excluded
      from the analysis. CONCLUSIONS: Chlamydia trachomatis infections are a
      significant health burden in Australia; however, accurate estimation of chlamydia
      prevalence in Australian sub-populations is limited by heterogeneity within
      surveyed populations, and variations in sampling methodologies and data
      reporting. There is a need for more large, population-based studies and
      prospective cohort studies to compliment mandatory notification data.

PMID- 22583479
TI  - Induction of the neural crest state: control of stem cell attributes by gene
      regulatory, post-transcriptional and epigenetic interactions.
AB  - Neural crest cells are a population of multipotent stem cell-like progenitors
      that arise at the neural plate border in vertebrates, migrate extensively, and
      give rise to diverse derivatives such as melanocytes, craniofacial cartilage and
      bone, smooth muscle, peripheral and enteric neurons and glia. The neural crest
      gene regulatory network (NC-GRN) includes a number of key factors that are used
      reiteratively to control multiple steps in the development of neural crest cells,
      including the acquisition of stem cell attributes. It is therefore essential to
      understand the mechanisms that control the distinct functions of such
      reiteratively used factors in different cellular contexts. The context-dependent
      control of neural crest specification is achieved through combinatorial
      interaction with other factors, post-transcriptional and post-translational
      modifications, and the epigenetic status and chromatin state of target genes.
      Here we review the current understanding of the NC-GRN, including the role of the
      neural crest specifiers, their links to the control of "stemness," and their
      dynamic context-dependent regulation during the formation of neural crest
      progenitors.

PMID- 22583484
TI  - Effect of erythropoietin-stimulating agent on uremic inflammation.
AB  - BACKGROUND: The goal of the present study was to explore the effect of
      medications that are commonly prescribed for CKD patients on uremic state.
      METHODS: This was a cross-sectional study. From January 2006 to October 2009,
      1,623 patients with end-stage kidney disease (ESKD) commenced hemodialysis (HD)
      at the 9 participating hospitals. The criteria for exclusion from the database
      were 1) serum C-reactive protein (CRP) > 3 mg/dL, 2) WBC count > 9,000/mm3 or
      <4,000/mm3, and 3) patients with cancer, immune complex disease, or vasculitis. A
      total of 900 patients were entered into the final database. We explored the
      association of serum CRP just before the first HD session with clinical
      characteristics, laboratory data, and medications for CKD in the predialysis
      period. RESULTS: On univariate analysis, age, CTR, eGFR, and WBC were
      significantly correlated with CRP. Systolic and diastolic blood pressure, serum
      albumin, LDL-C, HDL-C, Hb, Cr, and Ca were inversely associated with CRP. Use of
      erythropoietin-stimulating agents (ESA) using (r = -0.111, p = 0.0015), renin
      angiotensin-aldosterone system inhibitors (r = -0.083, p = 0.0154), and calcium
      channel blockers (r = -0.1, p = 0.0039) was also negatively correlated with CRP.
      However, only use of ESA showed a significant negative correlation with CRP that
      was independent of other clinical factors and CKD medications on multiple
      regression analysis. CONCLUSION: ESA may strongly reduce uremic inflammation in
      addition to improving anemia. To confirm this potential effect, a large-scale
      longitudinal study would be required.

PMID- 22583485
TI  - Comparisons of clustered regularly interspaced short palindromic repeats and
      viromes in human saliva reveal bacterial adaptations to salivary viruses.
AB  - Explorations of human microbiota have provided substantial insight into microbial
      community composition; however, little is known about interactions between
      various microbial components in human ecosystems. In response to the powerful
      impact of viral predation, bacteria have acquired potent defences, including an
      adaptive immune response based on the clustered regularly interspaced short
      palindromic repeats (CRISPRs)/Cas system. To improve our understanding of the
      interactions between bacteria and their viruses in humans, we analysed 13 977
      streptococcal CRISPR sequences and compared them with 2 588 172 virome reads in
      the saliva of four human subjects over 17 months. We found a diverse array of
      viruses and CRISPR spacers, many of which were specific to each subject and time
      point. There were numerous viral sequences matching CRISPR spacers; these matches
      were highly specific for salivary viruses. We determined that spacers and viruses
      coexist at the same time, which suggests that streptococcal CRISPR/Cas systems
      are under constant pressure from salivary viruses. CRISPRs in some subjects were
      just as likely to match viral sequences from other subjects as they were to match
      viruses from the same subject. Because interactions between bacteria and viruses
      help to determine the structure of bacterial communities, CRISPR-virus analyses
      are likely to provide insight into the forces shaping the human microbiome.

PMID- 22583486
TI  - Lipopolysaccharide biosynthesis genes discriminate between Rubus- and
      Spiraeoideae-infective genotypes of Erwinia amylovora.
AB  - Comparative genomic analysis revealed differences in the lipopolysaccharide (LPS)
      biosynthesis gene cluster between the Rubus-infecting strain ATCC BAA-2158 and
      the Spiraeoideae-infecting strain CFBP 1430 of Erwinia amylovora. These
      differences corroborate rpoB-based phylogenetic clustering of E. amylovora into
      four different groups and enable the discrimination of Spiraeoideae- and Rubus
      infecting strains. The structure of the differences between the two groups
      supports the hypothesis that adaptation to Rubus spp. took place after species
      separation of E. amylovora and E. pyrifoliae that contrasts with a recently
      proposed scenario, based on CRISPR data, in which the shift to domesticated apple
      would have caused an evolutionary bottleneck in the Spiraeoideae-infecting
      strains of E. amylovora which would be a much earlier event. In the core region
      of the LPS biosynthetic gene cluster, Spiraeoideae-infecting strains encode three
      glycosyltransferases and an LPS ligase (Spiraeoideae-type waaL), whereas Rubus
      infecting strains encode two glycosyltransferases and a different LPS ligase
      (Rubus-type waaL). These coding domains share little to no homology at the amino
      acid level between Rubus- and Spiraeoideae-infecting strains, and this genotypic
      difference was confirmed by polymerase chain reaction analysis of the associated
      DNA region in 31 Rubus- and Spiraeoideae-infecting strains. The LPS biosynthesis
      gene cluster may thus be used as a molecular marker to distinguish between Rubus-
      and Spiraeoideae-infecting strains of E. amylovora using primers designed in this
      study.

PMID- 22583487
TI  - Reports of past alcohol and drug use following participation in a motivation
      enhancing intervention: implications for clinical assessment and program
      evaluation.
AB  - BACKGROUND: There is significant interest in the value of motivational approaches
      that enhance participant readiness to change, but less is known about clients'
      self-reports of problematic behavior when participating in such interventions.
      METHODS: We examined whether participants in a motivationally-based intervention
      for DUI offenders changed their reports of substance use at postintervention
      (when reporting on the same 30 days that they reported on at preintervention).
      Specifically, Study 1 (N = 8,387) tested whether participants in PRIME For Life
      (PFL) changed their reports about baseline substance levels when asked at
      postintervention versus at preintervention. Study 2 (N = 192) compared changes in
      self-reported baseline drinking between PFL and intervention as usual (IAU)
      participants. RESULTS: Many participants in Study 1 did not change their reports
      about how much they used substances during the 30-day period before baseline.
      Among those who did, the most common change was an increase in reported amounts
      of baseline drug use, and typical and peak alcohol use. This sample also showed
      changes in reports of their baseline pattern of high-risk-use (consistent versus
      occasional). At postintervention, participants who were younger, single, or
      endorsing more indicators of alcohol dependence were more likely to later report
      greater frequency of baseline drug use, and greater peak and typical number of
      baseline drinks. Gender, education, and race were also associated with reporting
      inconsistency on some behaviors. In Study 2, PFL participants showed greater
      increases in reports of peak alcohol use compared to IAU, but both conditions
      showed similar increases for drugs and typical alcohol use. CONCLUSIONS: In both
      research and clinical settings, a segment of participants may initially report
      less substance use than they do when asked later about the same baseline period.
      These preliminary findings suggest clinicians and researchers may find
      postintervention evaluations yield reports of greater baseline alcohol or drug
      use for some people. For some behaviors, this may occur more often in
      interventions that target client motivation. Future research should attempt to
      identify which reports - preintervention vs. postintervention - better reflect
      actual baseline substance use.

PMID- 22583489
TI  - Oxidation of dibenzothiophene (DBT) by Serratia marcescens UCP 1549 formed
      biphenyl as final product.
AB  - BACKGROUND: The desulphurization of dibenzothiophene (DBT), a recalcitrant
      thiophenic fossil fuel component by Serratia marcescens (UCP 1549) in order for
      reducing the Sulphur content was investigated. The Study was carried out
      establishing the growth profile using Luria Bertani medium to different
      concentrations of DBT during 120 hours at 28 degrees C, and orbital Shaker at 150
      rpm. RESULTS: The results indicated that concentrations of DBT 0.5, 1.0 and 2.0
      mM do not affected the growth of the bacterium. The DBT showed similar Minimum
      Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MCB) (3.68
      mM). The desulphurization of DBT by S. marcescens was used with 96 hours of
      growth on 2 mM of DBT, and was determined by gas chromatography (GC) and GC-mass
      spectrometry. In order to study the desulphurization process by S. marcescens was
      observed the presence of a sulfur-free product at 16 hours of cultivation.
      CONCLUSIONS: The data suggests the use of metabolic pathway "4S" by S. marcescens
      (UCP 1549) and formed biphenyl. The microbial desulphurization process by
      Serratia can be suggest significant reducing sulphur content in DBT, and showed
      promising potential for reduction of the sulfur content in diesel oil.

PMID- 22583488
TI  - 3DMolNavi: a web-based retrieval and navigation tool for flexible molecular shape
      comparison.
AB  - BACKGROUND: Many molecules of interest are flexible and undergo significant shape
      deformation as part of their function, but most existing methods of molecular
      shape comparison treat them as rigid shapes, which may lead to incorrect measure
      of the shape similarity of flexible molecules. Currently, there still is a
      limited effort in retrieval and navigation for flexible molecular shape
      comparison, which would improve data retrieval by helping users locate the
      desirable molecule in a convenient way. RESULTS: To address this issue, we
      develop a web-based retrieval and navigation tool, named 3DMolNavi, for flexible
      molecular shape comparison. This tool is based on the histogram of Inner Distance
      Shape Signature (IDSS) for fast retrieving molecules that are similar to a query
      molecule, and uses dimensionality reduction to navigate the retrieved results in
      2D and 3D spaces. We tested 3DMolNavi in the Database of Macromolecular Movements
      (MolMovDB) and CATH. Compared to other shape descriptors, it achieves good
      performance and retrieval results for different classes of flexible molecules.
      CONCLUSIONS: The advantages of 3DMolNavi, over other existing softwares, are to
      integrate retrieval for flexible molecular shape comparison and enhance
      navigation for user's interaction. 3DMolNavi can be accessed via
      https://engineering.purdue.edu/PRECISE/3dmolnavi/index.html.

PMID- 22583490
TI  - Balancing the use of guidelines and individualized care.

PMID- 22583494
TI  - Lithium reduces BACE1 overexpression, beta amyloid accumulation, and spatial
      learning deficits in mice with traumatic brain injury.
AB  - Traumatic brain injury (TBI) leads to both acute injury and long-term
      neurodegeneration, and is a major risk factor for developing Alzheimer's disease
      (AD). Beta amyloid (Abeta) peptide deposits in the brain are one of the
      pathological hallmarks of AD. Abeta levels increase after TBI in animal models
      and in patients with head trauma, and reducing Abeta levels after TBI has
      beneficial effects. Lithium is known to be neuroprotective in various models of
      neurodegenerative disease, and can reduce Abeta generation by modulating glycogen
      synthase kinase-3 (GSK-3) activity. In this study we explored whether lithium
      would reduce Abeta load after TBI, and improve learning and memory in a mouse TBI
      model. Lithium chloride (1.5 mEq/kg, IP) was administered 15 min after TBI, and
      once daily thereafter for up to 3 weeks. At 3 days after injury, lithium
      attenuated TBI-induced Abeta load increases, amyloid precursor protein (APP)
      accumulation, and beta-APP-cleaving enzyme-1 (BACE1) overexpression in the corpus
      callosum and hippocampus. Increased Tau protein phosphorylation in the thalamus
      was also attenuated after lithium treatment following TBI at the same time point.
      Notably, lithium treatment significantly improved spatial learning and memory in
      the Y-maze test conducted 10 days after TBI, and in the Morris water maze test
      performed 17-20 days post-TBI, in association with increased hippocampal
      preservation. Thus post-insult treatment with lithium appears to alleviate the
      TBI-induced Abeta load and consequently improves spatial memory. Our findings
      suggest that lithium is a potentially useful agent for managing memory
      impairments after TBI or other head trauma.

PMID- 22583496
TI  - Recognising our emerging researchers.

PMID- 22583495
TI  - Over-seasons analysis of quantitative trait loci affecting phenolic content and
      antioxidant capacity in raspberry.
AB  - This study examined the total phenol content (TPC) and total anthocyanin content
      (TAC) in ripe fruit of progeny of a mapping population generated from a cross
      between the European red raspberry cv. Glen Moy ( Rubus ideaus var. idaeus) and
      the North American red raspberry cv. Latham ( Rubus ideaus var. strigosus) over
      five seasons in two different growing environments. Measurements of antioxidant
      capacity (FRAP and TEAC) were also carried out. TPC was highly correlated with
      TEAC and FRAP across the entire data set. The subset of anthocyanin content was
      genotype-dependent but also correlated with TPC, although the proportion of
      anthocyanin compounds varied between progeny. Quantitative trait locus (QTL)
      analysis was carried out, and key markers were tested for consistency of effects
      over sites and years. Four regions, on linkage groups 2, 3, 5, and 6, were
      identified. These agree with QTLs from a previous study over a single season and
      indicate that QTL effects were robust over seasons.

PMID- 22583497
TI  - Situating forensic traces in time.
AB  - Situating events and traces in time is an essential problem in investigations. To
      date, among the typical questions issued in forensic science, time has generally
      been unexplored. The reason for this can be traced to the complexity of the
      overall problem, addressed by several scientists in very limited projects usually
      stimulated by a specific case. Considering that such issues are recurrent and
      transcending the treatment of each trace separately, the formalisation of a
      framework to address dating issues in criminal investigation is undeniably
      needed. Through an iterative process consisting of extracting recurrent aspects
      discovered from the study of problems encountered by practitioners and reported
      in the literature, common mechanisms were extracted and provide understanding of
      underlying factors encountered in forensic practise. Three complementary
      approaches are thus highlighted and described to formalise a preliminary
      framework that can be applied for the dating of traces, objects, persons and
      indirectly events.

PMID- 22583498
TI  - The fallacy of the two-minute acid phosphatase cut off.
AB  - Research was carried out to determine whether the likelihood of obtaining a
      positive Acid Phosphatase (AP) test result is affected by the make and type of
      paper used. Also, we aimed to investigate the frequency of AP positive reactions
      occurring after 2min using a series of known semen dilutions and to determine
      whether spermatozoa transfer onto the paper during the act of AP screening. In
      this research, most brands of paper tested were able to detect a 1 in 40 semen
      dilution within 2min. Leaving AP test papers for longer will allow the detection
      of greater dilutions of semen and as the amount of ejaculation is not reliably
      known in most casework situations and levels of AP activity can vary in different
      men, this will increase the seminal detection rate in sexual offence allegations.

PMID- 22583499
TI  - Dichroism measurements in forensic fibre examination. Part 4-dyed acrylic and
      acetate fibres.
AB  - A number of dyed acrylic and acetate fibre samples were examined with plane
      polarized light on their dichroic behavior by optical light microscopy (OLM) and
      microspectrophotometry with plane polarized light (MSP-PPL). It was found that
      most of these low birefringent fibres possess weak dichroic effects that are very
      hard to observe with microscopy. However, using MSP-PPL, the linear dichroism
      could be measured. A comparison between the dichroic effects found for the same
      disperse dyes on triacetate (TrAc), diacetate (Ac), polyester (PES) and polyamide
      (PA) shows that the linear dichroism follows the order: PA>PES >>TrAc, Ac.

PMID- 22583501
TI  - A survey of paint flakes on the clothing of persons suspected of involvement in
      crime.
AB  - A survey was undertaken to determine the background level of paint flakes on the
      clothing of persons suspected of involvement in crime. The debris from 100
      garments submitted for casework examination was studied and paint flakes
      recovered where present. Seventy two percent of garments bore one or more flakes.
      A total of 703 flakes were recovered; size, topcoat colour, and number and colour
      of any under-layers were recorded for each. The distribution of paint flakes on
      clothing surfaces and in pockets was also noted. Results were compared with the
      previously published survey of Pearson, May and Dabbs (1971). This survey
      provides scientists with an updated data set for reference when considering the
      strength of paint evidence.

PMID- 22583500
TI  - Forensic identification of urine using the DMAC test: a method validation study.
AB  - Forensic scientists may sometimes be asked to identify the presence of urine in
      cases such as harassment, rape or murder. One popular presumptive test method
      uses para-dimethylaminocinnamaldehyde (DMAC), favoured because it is simple,
      rapid and safe. This paper confirms that DMAC reacts with urea rather than
      creatinine, ammonia or uric acid. Sensitivity studies found that the 0.1% w/v
      DMAC solution currently used for urine identification detects levels of urea
      found in other body fluids, potentially resulting in false positives. A 0.05% w/v
      solution was found to be more appropriate in terms of sensitivity to urea however
      the test is still not specific for urine, giving positive reactions with a number
      of body fluids (saliva, semen, sweat and vaginal material) and other substances
      (foot lotion, hair removal cream and broccoli).

PMID- 22583502
TI  - Black and green tea - luminol false-negative bloodstains detection.
AB  - The antioxidant properties of black and green teas are well known. It is also
      possible to determine their antioxidant capacity by using a chemiluminscent
      method. This method is based on the measurement of the delay in the emission of
      light from the luminol reaction in the presence of the antioxidant. Bloodstains
      which are invisible to the naked eye can also be detected by luminol. Three
      common methods (detection using the Grodsky or Weber formulations and by
      Bluestar(r) Forensic latent bloodstain reagent) are based on the luminol
      chemiluminescence reaction. The bloodstains can be masked by drinks and/or foods
      containing antioxidants. The aim of this work was to compare the ability of black
      and green teas containing antioxidants to cause false negative results during
      chemiluminescent bloodstain detection.

PMID- 22583503
TI  - Acid phosphatase screening - wetting test paper or wetting fabric and test paper?
AB  - Detecting and locating semen stains is addressed by identifying the associated
      acid phosphatase activity of semen. The recovery of semen stains is critical as
      it can, via DNA testing, address the possible source(s) of the semen and may aid
      in the interpretation of a case. The purpose of these experiments, carried out on
      behalf of the Body Fluids Forum, was to consider whether wetting the test paper
      alone or wetting the semen stained fabric and the test paper affected the
      detection and location of the semen stains on various fabric types, or the
      subsequent recovery of spermatozoa from these fabrics. It became evident that the
      preferred approach varied depending on the fabric type being tested but that more
      often than not, wetting both the fabric and the test paper had a detrimental
      effect on the recovery of spermatozoa.

PMID- 22583504
TI  - Determination of the sequence of intersecting lines from laser toner and seal ink
      by Fourier transform infrared microspectroscopy and scanning electron microscope
      / energy dispersive X-ray mapping.
AB  - The aim of this study was to verify that the combination of Fourier transform
      infrared microspectroscopy and scanning electron microscope / energy dispersive X
      ray mapping could be applied to line intersection problems. The spectral data of
      red seal ink, laser toner and their intersections, such as peak location and peak
      intensity, were described. Relative peak height ratios of different chemical
      components in intersecting lines were used to distinguish the sequences. Energy
      dispersive X-ray mapping characteristics of intersecting areas were also
      detailed. The results show that both the laser toner and the seal ink appear on
      the surface of intersections, regardless of the sequence. The distribution of the
      two inks on the surface is influenced not only by the sequence of heterogeneous
      lines but also by diffusion. Fourier transform infrared microspectroscopy and
      scanning electron microscope/energy dispersive X-ray mapping are able to explore
      the chemical components and the corresponding elemental distribution in the
      intersections. The combination of these two techniques has provided a reliable
      method for sequencing intersecting lines of red seal ink and laser toner, and
      more importantly, this method may be a basis for sequencing superimposed lines
      from other writing instruments.

PMID- 22583505
TI  - A competence assessment framework for scientific support within policing in
      England and Wales.
AB  - The Association of Chief Police Officers commissioned Skills for Justice to
      develop a competence assessment framework to support police forces' scientific
      support units evidence the competence of their staff against nationally agreed
      standards of competence. This will also help forces on their journey towards ISO
      17025 and ISO 17020 accreditation. A six point framework has been developed and
      published and is now being implemented across many forces.

PMID- 22583506
TI  - The design of "the first experimental study exploring DNA interpretation".
AB  - This letter explains why a recent study purporting to show that exposure to
      domain-irrelevant information caused DNA analysts to misinterpret a complex
      mixture does not warrant this conclusion on the basis of the data from the study.

PMID- 22583508
TI  - RE. 'subjectivity and bias in forensic DNA mixture interpretation' (Dror and
      Hapikian Volume 51 Issue 4).

PMID- 22583510
TI  - Post-partum pituitary insufficiency and livedo reticularis presenting a
      diagnostic challenge in a resource limited setting in Tanzania: a case report,
      clinical discussion and brief review of existing literature.
AB  - BACKGROUND: Pituitary disorders following pregnancy are an important yet under
      reported clinical entity in the developing world. Conversely, post partum
      panhypopituitarism has a more devastating impact on women in such settings due to
      high fertility rates, poor obstetric care and scarcity of diagnostic and
      therapeutic resources available. CASE PRESENTATION: A 37 year old African female
      presented ten years post partum with features of multiple endocrine deficiencies
      including hypothyroidism, hypoadrenalism, lactation failure and secondary
      amenorrhea. In addition she had clinical features of an underlying autoimmune
      condition. These included a history of post-partum thyroiditis, alopecia areata,
      livedo reticularis and deranged coagulation indices. A remarkable clinical
      response followed appropriate hormone replacement therapy including steroids.
      This constellation has never been reported before; we therefore present an
      interesting clinical discussion including a brief review of existing literature.
      CONCLUSION: Post partum pituitary insufficiency is an under-reported condition of
      immense clinical importance especially in the developing world. A high clinical
      index of suspicion is vital to ensure an early and correct diagnosis which will
      have a direct bearing on management and patient outcome.

PMID- 22583511
TI  - Social contact patterns and leprosy disease: a case-control study in Bangladesh.
AB  - Socioeconomic and culturally defined social contact patterns are expected to be
      an important determinant in the continuing transmission of Mycobacterium leprae
      in leprosy-endemic areas. In a case-control study in two districts in Bangladesh,
      we assessed the association between social contact patterns and the risk of
      acquiring clinical leprosy. Social contacts of 90 recently diagnosed patients
      were compared to those of 199 controls. Leprosy was associated with a more
      intensive social contact pattern in the home [odds ratio (OR) 1.09, 95%
      confidence interval (CI) 1.00-1.19, P = 0.043] and in the nearby neighbourhood
      (OR 1.07, 95% CI 1.03-1.11, P = 0.001). Although it is known that M. leprae
      spreads most easily within households of infected persons, in endemic areas
      social contacts within the neighbourhood, village or urban ward, also appear to
      be important for transmission. We advise that disease control measures in leprosy
      endemic areas should not be limited to households, but include high-risk groups
      in the nearby neighbourhood of patients.

PMID- 22583514
TI  - Despite triple vaccination.

PMID- 22583513
TI  - Biomechanical properties of isolated fascicles of the Iliopsoas and Achilles
      tendons in African American and Caucasian men.
AB  - OBJECTIVES: To investigate biomechanical properties of the Iliopsoas and Achilles
      tendons in young African American (AA) and Caucasian (CC) men, and attempt to
      clarify whether the difference in Achilles tendon ruptures between AA and CC can
      be explained by differences in material properties. METHODS: Tissue from 12 young
      males (AA, n=6; CC, n=6) was obtained from routine forensic autopsies. Iliopsoas
      and Achilles tendon samples were obtained from cadavers that were age, height and
      weight matched. Tendon collagen fascicles were tested micromechanically in a
      Deben mechanical testing rig. RESULTS: Peak failure stress in Iliopsoas tendon
      fascicles was considerably higher (p<0.05) in AA (22.4 +/- 7.2MPa) than CC (6.8
      +/- 2.1MPa) whereas peak strain did not differ (AA: 19.7 +/- 5.2%, CC: 18.3 +/-
      3.5%). Likewise, Young's modulus was greater (p<0.05) in AA (165.3 +/- 67.3MPa)
      than CC (63.6 +/- 23.6MPa). In contrast, peak failure stress in Achilles tendon
      fascicles was similar (p>0.1) in AA (21.9 +/- 9.9MPa) and CC (28.1 +/- 9.8MPa),
      and peak strain did not differ (p>0.1) between AA (16.3 +/- 3.5%) and CC (13.8 +/
      4.4%). Young's modulus was slightly greater in CC (316.8 +/- 110MPa) than AA
      (222.8 +/- 84.6MPa), yet not significantly (p>0.1). CONCLUSIONS: These findings
      indicate that Iliopsoas tendon fascicles are stronger in young AA compared to CC
      males, which is suggested to reflect differences in muscle mass and force
      generating capacity. This could not be confirmed in Achilles tendon fascicles.

PMID- 22583512
TI  - Transthoracic Echocardiography with Doppler Tissue Imaging predicts weaning
      failure from mechanical ventilation: evolution of the left ventricle relaxation
      rate during a spontaneous breathing trial is the key factor in weaning outcome.
AB  - INTRODUCTION: There is growing evidence to suggest that transthoracic
      echocardiography (TTE) should be used to identify the cardiac origin of
      respiratory weaning failure. THE AIMS OF OUR STUDY WERE: first, to evaluate the
      ability of transthoracic echocardiography, with mitral Doppler inflow E velocity
      to annular tissue Doppler Ea wave velocity (E/Ea) ratio measurement, to predict
      weaning failure from mechanical ventilation in patients, including those with
      atrial fibrillation; and second, to determine whether the depressed left ejection
      fraction and/or diastolic dysfunction participate in weaning outcome. METHODS:
      The sample included patients on mechanical ventilation for over 48 hours. A
      complete echocardiography was performed just before the spontaneous breathing
      trial (SBT) and 10 minutes after starting the SBT. Systolic dysfunction was
      defined by a left ventricle ejection fraction under 50% and relaxation impairment
      by a protodiastolic annulus mitral velocity Ea under or equal to 8 cm/second.
      RESULTS: A total of 68 patients were included. Twenty failed the weaning process
      and the other 48 patients succeeded. Before the SBT, the E/Ea ratio was higher in
      the failed group than in the successful group. The E/Ea measured during the SBT
      was also higher in the failed group. The cut-off value, obtained from receiver
      operating characteristics (ROC) curve analysis, to predict weaning failure gave
      an E/Ea ratio during the SBT of 14.5 with a sensitivity of 75% and a specificity
      of 95.8%. The left ventricular ejection fraction did not differ between the two
      groups whereas Ea was lower in the failed group. Ea increased during SBT in the
      successful group while no change occurred in the failed group. CONCLUSIONS:
      Measurement of the E/Ea ratio with TTE could predict weaning failure. Diastolic
      dysfunction with relaxation impairment is strongly associated with weaning
      failure. Moreover, the impossibility of enhancing the left ventricle relaxation
      rate during the SBT seems to be the key factor of weaning failure. In contrast,
      the systolic dysfunction was not associated with weaning outcome.

PMID- 22583515
TI  - ADAM33 polymorphisms, smoking and asthma in Japanese women: the Kyushu Okinawa
      Maternal and Child Health Study.
AB  - SETTING: Multiple A disintegrin and metalloprotease 33 (ADAM33) single nucleotide
      polymorphisms (SNPs) have been shown to be associated with asthma, but results
      have been inconsistent. OBJECTIVES: To examine the association between ADAM33
      SNPs rs2787094, rs628977, rs2280089,  rs2280090, rs2280091, rs2853209, rs528557
      and rs612709 and asthma in young adult Japanese women, and to perform haplotype
      analyses and assess interactions between SNPs and smoking. DESIGN: A total of 89
      cases who met the criteria of the European Community Respiratory Health Survey
      (ECRHS)  for asthma were included in the study. Control subjects were 1281 women
      without asthma, as per ECRHS criteria, who had not been diagnosed with asthma by
      a doctor. Adjustment was made for age, region of residence, presence of older
      siblings, smoking and education. RESULTS: Under a co-dominant  model, the AA
      genotype of the rs612709 SNP was significantly positively associated with asthma
      compared with the GG genotype: the adjusted OR was 4.27 (95%CI 1.49-12.25). A
      significant positive relationship was found between the CCGGAAGA haplotype and
      asthma. Interactions between SNPs  rs628977 and rs528557 and smoking were
      marginally significant (P = 0.09 and 0.095, respectively). CONCLUSIONS: ADAM33
      SNP rs612709 and the CCGGAAGA haplotype may be associated with asthma. Smoking
      may modify the associations between SNPs rs628977 and rs528557 and asthma.

PMID- 22583516
TI  - HLA-DRB, -DQA, and DQB alleles and haplotypes in Iranian patients with diabetes
      mellitus type I.
AB  - Specific alleles at the HLA-DRB1, -DQA1, and -DQB1 loci seem to be associated
      with variable risks of developing type 1 diabetes (T1D). This study assessed the
      distribution of HLA-DR and -DQ alleles among Iranian T1D patients and healthy
      controls. In this study, HLA-DRB1, -DQA1, and -DQB1 alleles were determined in
      100 children with T1D and 100 unrelated healthy controls. The following alleles
      were found to have a strong positive association with T1D: DRB1*0301, DRB1*0401,
      DRB1*0402, DQA1*0301, DQA1*0501, DQB1*0201, and DQB1*0302. Meanwhile, protective
      associations were found for DRB1*1001, DRB1*1101, DRB1*15, DRB1*16, DQA1*0102,
      DQA1*0103, DQB1*0301, DQB1*0501, and DQB1*0602 alleles. The haplotypes found most
      frequently among patients with T1D were DRB1*0301-DQA1*0501-DQB1*0201, DRB1*0401
      DQA1*0301- DQB1*0302, and DRB1*0402-DQA1*0301-DQB1*0302, whereas DRB1*1101
      DQA1*0501-DQB1*0301 and DRB1*16-DQA1*0102- DQB1*0501 haplotypes were negatively
      associated with the disease. These results confirm the previously reported
      association of specific HLA-DR and HLA-DQ alleles and haplotypes with T1D in
      Iranian population. The notable difference was the identification of DRB1*16
      DQA1*0102-DQB1*0501 as a protective haplotype and the absence of a negative
      association of DRB1*1301-DQA1*0103-DRB1*0603 with T1D. 

PMID- 22583517
TI  - Current practices of partner notification among MSM with HIV, gonorrhoea and
      syphilis in the Netherlands: an urgent need for improvement.
AB  - BACKGROUND: Partner notification (PN) among individuals newly diagnosed with
      HIV/STI is seen as a vital tool to identify others at risk of infection. However,
      hardly any data are available on the effectiveness of PN on HIV/STI transmission
      in the Netherlands. This study aims to fill this gap by assessing current PN
      practices, case-finding effectiveness, and determinants of being notified among
      men having sex with men (MSM) in the Netherlands. METHODS: Nurses from five STI
      centers participated in a prospective pilot study on PN outcomes (partners being:
      at risk, notifiable, notified, and tested) for HIV/STI, by completing a newly
      developed PN registration form (PN database). PN outcomes including case-finding
      effectiveness (number of newly diagnosed cases in partners/number of partners
      being tested) for HIV, syphilis, and gonorrhoea were studied among MSM.
      Furthermore, the national STI database was analyzed to identify determinants of
      being notified. The number of infections that remained undetected was estimated
      based on these two databases. RESULTS: In total 105 MSM, newly diagnosed with
      HIV/STI, reported 612 sexual partners at risk of whom 41% were notifiable and 31%
      were notified. Patient referral was the predominant PN method (90%). The overall
      case-finding percentage was 36% (HIV: 15-33%, gonorrhoea: 17-50% and syphilis: 4
      11%). Case-finding percentages were lower in the national STI database: 21% (5%,
      28%, 12%). Persons with one or more sexual partners, known HIV positives, and IDU
      were more likely to be notified to the STI clinic. Notified clients were more
      likely to have HIV/STI than unnotified clients (OR 1.7-2.5). Based on these two
      databases, an estimated 75 to 133 infections remained undetected (HIV: 12-90;
      gonorrhoea: 28-97; syphilis: 5-12 infections). CONCLUSIONS: Partner notification
      among MSM in the Netherlands is suboptimal; an extensive number of STI/HIV
      infections remained undetected mainly due to unnotifiable partners. To enhance PN
      practices, combined and innovative PN interventions such as Internet-based PN
      will be implemented for hard-to-reach MSM and other risk groups.

PMID- 22583518
TI  - Characteristics of a sharp decrease in Vibrio parahaemolyticus infections and
      seafood contamination in Japan.
AB  - Vibrio parahaemolyticus has been one of the most important foodborne pathogens in
      Japan since the 1960s, and a large epidemic was caused by the pandemic serotype
      O3:K6 from 1997 to 2001. V. parahaemolyticus infections, however, have sharply
      declined since that time. Data on serotypes isolated from 977 outbreaks were
      collected and analysed. Total and pathogenic, thermostable direct hemolysin (TDH)
      gene-positive V. parahaemolyticus were qualitatively and quantitatively detected
      in 842 seafood samples from wholesale markets in 2007-2009. Strains isolated from
      patients and seafood were analysed by serotyping, tdh-PCR, group-specific PCR for
      pandemic strains, and pulsed-field gel electrophoresis (PFGE). The sharp decrease
      in the infections from 1999 onwards was noted not only for O3:K6 infections but
      also for other serotypes. The change in the seafood contamination situation from
      2001 to 2007-2009 was characterised by a decrease to three-fourths in the
      frequency of tdh-positive samples, although that decrease was small compared to
      the 18-fold decrease in the cases of V. parahaemolyticus outbreaks. PFGE detected
      the pandemic O3:K6 serotype in the same profile in seafood and patients from 1998
      to the present. Because of no large decrease in seafood contamination by V.
      parahaemolyticus from the production to distribution stages and the presence of
      pandemic O3:K6 serotype in seafood to the present, it was suggested that the
      change of seafood contamination was unrelated to the sharp decrease in V.
      parahaemolyticus infections. V. parahaemolyticus infections might be prevented at
      the stages after the distribution stage.

PMID- 22583519
TI  - The housekeeping gene YWHAZ remains stable in a model of developmentally primed
      non-alcoholic fatty liver disease.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common form of
      chronic liver disease in Western society. Comparative gene expression studies are
      beginning to elucidate the molecular mechanisms underlying NAFLD progression. We
      have previously shown that high fat diets during early life can prime non
      alcoholic steatohepatitis (NASH) in adulthood, through lipogenesis gene
      elevation. To generate accurate results in such studies, appropriate housekeeping
      genes (HKG) which are unaffected by disease processes, are used for data
      normalisation. However, there is little existing data to show the effects of
      NAFLD on HKG expression. AIMS: To identify the HKG in a mouse model of
      developmentally primed NAFLD and NASH, which maintains expression stability.
      METHODS: We determined the expression stability of six candidates HKG (GAPDH,
      YWHAZ, B2M, EIF4A2, ACTB and CYC1) in a mouse model of developmentally primed
      NAFLD in both the day and night, using geNORM qBasePlus software. RESULTS: HKG
      expression differed across dietary groups and time of day. In the majority of
      treatment groups and time points the most stable gene was YWHAZ. Following high
      fat diet interventions CYC1 became notably unstable. Overall the effect of NAFLD
      and NASH on HKG expression was to maintain stability of YWHAZ, but destabilise
      CYC1 and EIF4A2. CONCLUSIONS: Our data clearly shows that HKG expression is
      affected by NAFLD severity and time of day sampling, highlighting the importance
      of suitable HKG gene selection. For comparative gene expression studies
      investigating NAFLD we would recommend use of YWHAZ as a robust, stably expressed
      HKG.

PMID- 22583521
TI  - Multidisciplinary stroke management.

PMID- 22583520
TI  - Online self-administered training for post-traumatic stress disorder treatment
      providers: design and methods for a randomized, prospective intervention study.
AB  - This paper presents the rationale and methods for a randomized controlled
      evaluation of web-based training in motivational interviewing, goal setting, and
      behavioral task assignment. Web-based training may be a practical and cost
      effective way to address the need for large-scale mental health training in
      evidence-based practice; however, there is a dearth of well-controlled outcome
      studies of these approaches. For the current trial, 168 mental health providers
      treating post-traumatic stress disorder (PTSD) were assigned to web-based
      training plus supervision, web-based training, or training-as-usual (control). A
      novel standardized patient (SP) assessment was developed and implemented for
      objective measurement of changes in clinical skills, while on-line self-report
      measures were used for assessing changes in knowledge, perceived self-efficacy,
      and practice related to cognitive behavioral therapy (CBT) techniques. Eligible
      participants were all actively involved in mental health treatment of veterans
      with PTSD. Study methodology illustrates ways of developing training content,
      recruiting participants, and assessing knowledge, perceived self-efficacy, and
      competency-based outcomes, and demonstrates the feasibility of conducting
      prospective studies of training efficacy or effectiveness in large healthcare
      systems.

PMID- 22583522
TI  - Is stroke incidence in low- to middle-income countries driven by economics?
AB  - The incidence of stroke in low- to middle-income countries now exceeds that in
      high-income countries. These low- to middle-income countries also have greater
      case fatality and a younger age of stroke onset, factors that contribute to a
      high stroke burden. Macroeconomic indicators of socioeconomic status, such as
      health expenditure, appear to be inversely associated with stroke incidence.
      However, there are often large socioeconomic gradients between regions such as
      between urban and rural regions. This article emphasizes that macroeconomic
      indicators are likely to mask regional disparities in stroke incidence. Public
      health messages and prevention strategies must therefore be targeted regionally
      rather than nationwide. Without a comprehensive and multifaceted approach to
      prevention, the epidemic of stroke will continue.

PMID- 22583523
TI  - Collateral perfusion: time for novel paradigms in cerebral ischemia.
AB  - Collateral circulation and associated potential compensation in downstream
      perfusion have been recognized long before arterial occlusions were known to
      cause ischemic stroke. Arterial aspects and the venous capacity of collaterals to
      offset potentially devastating effects of blocking a cerebral artery have been
      studied in various animal species and even human populations with stroke,
      providing a framework for translational research. The time has come for
      collaterals to move from the periphery to a central position in stroke
      therapeutics, propelled by the momentum of imaging data and culminating in novel
      paradigms with respect to time, imaging approaches and treatment strategies. It
      is time for a concerted focus on collateral perfusion to harness potential
      therapeutic advances from acute stroke to chronic cerebrovascular disorders.

PMID- 22583524
TI  - Lower incidence of vascular events following small artery ischemic stroke.

PMID- 22583525
TI  - French adaptation of the vascular cognitive impairment harmonization standards:
      the GRECOG-VASC study.

PMID- 22583526
TI  - Trends in the use of intravenous recombinant tissue plasminogen activator from
      northwest India.

PMID- 22583527
TI  - Extracranial color duplex sonography as a first tool in the prognosis after
      thrombolytic therapy.

PMID- 22583528
TI  - Tunable fabrication on iron oxide/Au/Ag nanostructures for surface enhanced Raman
      spectroscopy and magnetic enrichment.
AB  - A facile approach was developed to prepare novel multifunctional Fe(2)O(3)/Au/Ag
      nanostructures integrated with isolated functions involving magnetic and optical
      properties. The Fe(2)O(3)/Au/Ag hybrid nanoparticles with different thicknesses
      of Ag shell were prepared by adjusting the amount of the AgNO(3). Surface
      structures were varied from the rough with pinhole to smooth and pinhole free
      surfaces with increasing amounts of AgNO(3). The surface plasmon resonance was
      tuned in a very wide region from that of Au to Ag. Surface enhanced Raman
      scattering (SERS) effects were also investigated, employing thiophenol (TP) and
      aminothiophenol (PATP) as probe molecules. It was revealed that the SERS
      intensity was strongly depended on the molar ratio of Ag and Au. With an increase
      in the Ag molar fractions, SERS signals were enhanced to the maximum due to the
      surface plasmon resonance of the pinhole structure. The magnetic enrichment for
      on line SERS monitoring the molecules with low concentration was performed based
      on the magnetic core and the SERS activity of the bimetallic shells. This
      enrichment procedure improved efficiently the limits of the SERS detection. It
      was shown that the multicomponent nanoparticles have potential applications in
      the fields of optical devices and magnetic separation.

PMID- 22583529
TI  - Assessment of endothelium and inflammatory response at the onset of reperfusion
      injury in hand surgery.
AB  - BACKGROUND: Activation of the endothelium, complement activation and generation
      of cytokines are known events during ischemia-reperfusion (I/R) that mediate
      tissue injury. Our aim was to elucidate their respective participation at the
      onset of the reperfusion phase. Tourniquet application in hand surgery causes
      short-term ischemia, followed by reperfusion and was therefore used as the model
      in this study. METHODS: Ten patients were included in the study after obtaining
      informed consent. A tourniquet was placed on the upper arm and inflated to 250
      mmHg for 116 +/- 16 min, during which the surgery was performed. Venous blood and
      tissue samples from the surgical area were taken at baseline as well as 0, 2, and
      10 min after reperfusion and analyzed for the following parameters: Endothelial
      integrity and/or activation were analyzed by measuring heparan sulfate and
      syndecan-1 in serum, and vWF, heparan sulfate proteoglycan as well as CD31on
      tissue. Complement activation was determined by C3a and C4d levels in plasma,
      levels of C1-inhibitor in serum, and IgG, IgM, C3b/c, and C4b/c deposition on
      tissue. Cytokines and growth factors IL-5, IL-6, IL-7, IL-8, IL-10, IL-17, G-CSF,
      GM-CSF, MCP-1, TNFalpha, VEGF, and PDGF bb were measured in the serum. Finally,
      CK-MM levels were determined in plasma as a measure for muscle necrosis. RESULTS:
      Markers for endothelial activation and/or integrity as well as complement
      activation showed no significant changes until 10 min reperfusion. Among the
      measured cytokines, IL-6, IL-7, IL-17, TNFalpha, GM-CSF, VEGF, and PDGF bb were
      significantly increased at 10 min reperfusion with respect to baseline. CK-MM
      showed a rise from baseline at the onset of reperfusion (p < 0.001) and dropped
      again at 2 min (p < 0.01) reperfusion, suggesting ischemic muscle damage.
      CONCLUSIONS: In this clinical model of I/R injury no damage to the endothelium,
      antibody deposition or complement activation were observed during early
      reperfusion. However, an increase of pro-inflammatory cytokines and growth
      factors was shown, suggesting a contribution of these molecules in the early
      stages of I/R injury.

PMID- 22583531
TI  - Road traffic crash injuries and fatalities in the city of Kerman, Iran.
AB  - The objective of this study was to investigate road traffic crash injuries and
      fatalities. Cases of 3902 road traffic injuries (1709 drivers, 891 passengers,
      376 pedestrians and 926 motorcyclists) and 1564 road traffic fatalities (RTFs;
      1222 males and 342 females) were collected from 2005 to 2008 using the database
      of the police forces and Department of Forensic Medicine in Kerman, respectively.
      Results showed that 66% of the injuries were related to car occupants (drivers
      and passengers) and men/women ratio was 5:1. The highest men/women ratio was
      (12.2:1) for drivers, while the lowest ratio (1.8:1) was for pedestrians. Most of
      the injuries had taken place at 16:01-20:00 h followed by 08:01-12:00 h. Highest
      numbers of injuries were found in male with the age groups of 18-24 years. The
      highest fatality rate of 79 per 100,000 population occurred in 2007-2008.
      Fatality ratio indicated higher male ratio, four times higher than females. The
      victims were 39% male between 30 and 55 years of age. Head injuries were present
      in 69% of the cases. In our series of forensic autopsy cases, head injuries were
      more frequent in motor vehicle occupants, pedestrians and motorcyclists. On
      average, two people died per day in RTFs in Kerman.

PMID- 22583530
TI  - SIS: a program to generate draft genome sequence scaffolds for prokaryotes.
AB  - BACKGROUND: Decreasing costs of DNA sequencing have made prokaryotic draft genome
      sequences increasingly common. A contig scaffold is an ordering of contigs in the
      correct orientation. A scaffold can help genome comparisons and guide gap closure
      efforts. One popular technique for obtaining contig scaffolds is to map contigs
      onto a reference genome. However, rearrangements that may exist between the query
      and reference genomes may result in incorrect scaffolds, if these rearrangements
      are not taken into account. Large-scale inversions are common rearrangement
      events in prokaryotic genomes. Even in draft genomes it is possible to detect the
      presence of inversions given sufficient sequencing coverage and a sufficiently
      close reference genome. RESULTS: We present a linear-time algorithm that can
      generate a set of contig scaffolds for a draft genome sequence represented in
      contigs given a reference genome. The algorithm is aimed at prokaryotic genomes
      and relies on the presence of matching sequence patterns between the query and
      reference genomes that can be interpreted as the result of large-scale
      inversions; we call these patterns inversion signatures. Our algorithm is capable
      of correctly generating a scaffold if at least one member of every inversion
      signature pair is present in contigs and no inversion signatures have been
      overwritten in evolution. The algorithm is also capable of generating scaffolds
      in the presence of any kind of inversion, even though in this general case there
      is no guarantee that all scaffolds in the scaffold set will be correct. We
      compare the performance of sis, the program that implements the algorithm, to
      seven other scaffold-generating programs. The results of our tests show that sis
      has overall better performance. CONCLUSIONS: sis is a new easy-to-use tool to
      generate contig scaffolds, available both as stand-alone and as a web server. The
      good performance of sis in our tests adds evidence that large-scale inversions
      are widespread in prokaryotic genomes.

PMID- 22583532
TI  - "It's just not cricket", or is it?

PMID- 22583533
TI  - Anti-apoptotic and anti-oxidative mechanisms of minocycline against
      sphingomyelinase/ceramide neurotoxicity: implication in Alzheimer's disease and
      cerebral ischemia.
AB  - Sphingolipids represent a major class of lipids in which selected family members
      act as bioactive molecules that control diverse cellular processes, such as
      proliferation, differentiation, growth, senescence, migration and apoptosis.
      Emerging evidence reveals that sphingomyelinase/ceramide pathway plays a pivotal
      role in neurodegenerative diseases that involve mitochondrial dysfunction,
      oxidative stress and apoptosis. Minocycline, a semi-synthetic second-generation
      tetracycline derivative in clinical use for infection control, is also considered
      an effective protective agent in various neurodegenerative diseases in pre
      clinical studies. Acting via multiple mechanisms, including anti-inflammatory,
      anti-oxidative and anti-apoptotic effects, minocycline is a desirable candidate
      for clinical trials in both acute brain injury as well as chronic
      neurodegenerative disorders. This review is focused on the anti-apoptotic and
      anti-oxidative mechanisms of minocycline against neurotoxicity induced by
      sphingomyelinase/ceramide in relation to neurodegeneration, particularly
      Alzheimer's disease and cerebral ischemia.

PMID- 22583534
TI  - Attentional bias for smoking-related information in pregnant women: relationships
      with smoking experience, smoking attitudes and perceived harm to foetus.
AB  - According to recent models of drug dependence, attentional bias for drug cues
      provides an index of vulnerability to drug-taking and relapse. The present study
      examined attentional bias for smoking-related information in pregnant women and
      its relationship with smoking experience and attitudes. Participants were 71
      pregnant women (35 without smoking experience; 36 with experience of smoking, of
      whom 16 reported currently smoking). Attentional bias was assessed from the
      interference index of smoking-related words on a modified Stroop task. The
      attentional bias for smoking cues was positively associated with smoking
      experience, and with more favourable general attitudes to smoking (i.e. incentive
      related bias). The bias was also greater in women who perceived greater harm of
      passive smoking to their foetus (i.e. threat-related bias), which was independent
      of smoking experience. Results indicate that attentional bias for smoking-related
      cues is independently associated with both incentive-related (reward) and threat
      related (aversive) evaluations of cigarette smoking in pregnant women. This work
      highlights the need for longitudinal research to investigate whether the
      attentional bias provides a cognitive index of vulnerability for persistent
      smoking behaviour both during and after pregnancy.

PMID- 22583535
TI  - Use of treatment strategies in a moderated drinking program for women.
AB  - Little is known about the extent to which individuals participating in drinking
      reduction interventions use the drinking reduction strategies presented during
      treatment. In consideration of this issue, we advanced hypotheses about the
      impact of baseline drinking patterns on strategy use and the relationship of
      strategy use to drinking patterns over time. One hundred forty-four women who
      participated in a 10-week drinking reduction program were monitored over an 18
      month posttreatment follow-up period. Results indicated that the frequency of
      baseline heavy drinking days and the frequency of baseline abstinent/light
      drinking days negatively predicted drinking reduction strategy use during
      treatment. Over the follow-up period, strategy use decreased; however,
      participants who received booster sessions had higher strategy use during the
      initial phase of follow-up. Although cross-lagged panel analysis revealed that
      strategy use during treatment predicted abstinent/light days at the 6-month
      follow-up assessment, this effect was moderated by baseline drinking patterns.
      These data indicated that the use of drinking reduction strategies is predictive
      of subsequent reduced drinking only in the early posttreatment period and only
      for baseline heavier drinkers. Future research is needed to further specify the
      interplay of strategy use and drinking outcomes and to develop interventions
      designed to encourage the continued use of strategies over extended periods of
      time.

PMID- 22583536
TI  - Methionine restriction affects the phenotypic and transcriptional response of
      rainbow trout (Oncorhynchus mykiss) to carbohydrate-enriched diets.
AB  - Mammalian studies report that methionine restriction (MR) as a dietary regimen
      extends life span, delays the onset of age-related diseases and enhances fat
      oxidation in obese subjects with metabolic syndromes. However, the underlying
      cellular signalling pathways are poorly understood. Rainbow trout (Oncorhynchus
      mykiss) is a glucose-intolerant species, providing an excellent model for the
      study of carbohydrate metabolism. MR diets in combination with 12 % (+/-) and 22
      % (+/-) carbohydrate-rich meals were fed to rainbow trout for a period of 8 weeks
      and phenotypic and transcript expression changes in the liver and white muscle
      were assessed. Fish fed MR diets, irrespective of carbohydrate load, were shown
      to abolish the glucose-intolerant phenotype 6 h post-feeding. There was a
      distinct switch in glucose and glycogen content in the liver of fish fed MR
      diets, with a significantly higher concentration of glycogen, suggesting reduced
      glycolytic capacity. Transcriptional responses to MR demonstrated decreased
      expression of hepatic fatty acid synthase, sterol regulatory binding protein 1,
      PPARgamma coactivator 1-alpha and PPARalpha, indicative of a reduction in the de
      novo synthesis of fatty acids and cholesterol, and a potential decrease in
      hepatic fat oxidative capacity. Muscle adenylate charge was depressed under MR,
      and increased expression of AMP-activated protein kinase alpha1 was detected,
      indicative of reduced energy availability. Total DNA methylation showed that
      carbohydrate load, rather than MR, dictated hypomethylation of genomic DNA. This
      is the first study which demonstrates that MR can abolish a glucose-intolerant
      phenotype in trout, and identifies trout as a suitable model for studying
      metabolic syndromes.

PMID- 22583537
TI  - Effects of ionic strength on the enzymatic hydrolysis of diluted and concentrated
      whey protein isolate.
AB  - To identify the parameters that affect enzymatic hydrolysis at high substrate
      concentrations, whey protein isolate (1-30% w/v) was hydrolyzed by Alcalase and
      Neutrase at constant enzyme-to-substrate ratio. No changes were observed in the
      solubility and the aggregation state of the proteins. With increasing
      concentration, both the hydrolysis rate and the final DH decreased, from 0.14 to
      0.015 s(-1) and from 24 to 15%, respectively. The presence of 0.5 M NaCl
      decreased the rate of hydrolysis for low concentrations (to 0.018 s(-1) for 1%
      WPI), resulting in similar rates of hydrolysis for all substrate concentrations.
      The conductivity increase (by increasing the protein concentration, or by
      addition of NaCl) has significant effects on the hydrolysis kinetics, but the
      reason for this is not yet well understood. The results show the importance of
      conductivity as a factor that influences the kinetics of the hydrolysis, as well
      as the composition of the hydrolysates.

PMID- 22583538
TI  - Impact of data source and time reference of functional status on hospital
      mortality prediction.
AB  - BACKGROUND: The study objective was to compare physical function documented in
      the medical records with interview data, and also to evaluate hospital mortality
      predictions using pre-admission and on-admission functional status derived from
      these two data sources. METHODS: A prospective cohort study of 1402 subjects aged
      65 years and older to the general medicine department of an acute care hospital
      was conducted. Patient-reported pre-admission and on-admission functional status
      for impairment in any of the five activities of daily living (ADLs) items
      (feeding, dressing, grooming, toileting and bathing), transferring and walking,
      were compared with those extracted from the medical records. For the purpose of
      mortality prediction, pre-admission and on-admission impairment in transferring
      from the two data sources were included in separate multivariable logistic
      regression models. We used a variable selection method that combines bootstrap
      resampling with stepwise backward elimination. RESULTS: For all ADL categories,
      the agreement between the data sources was good for pre-admission functional
      status (k: 0.53-0.75) but poor for on-admission status (k: 0.18-0.31). On
      admission impairment was higher in the medical records than at interview for all
      basic ADLs. Using interview data as the gold standard, although sensitivity for
      pre- and on-admission ADLs was high (59-93%), specificity for on-admission status
      was poor (30-37%). The pre-admission models using interview data predicted
      mortality better than the model using medical records (c-statistic: 0.83 versus
      0.82). Similar results were found for models incorporating on-admission
      functional status (c-statistic: 0.84 versus 0.81). However, the differences
      between the four models were not statistically significant. CONCLUSION: Medical
      records can be a good source for pre-admission functional status but on-admission
      functional impairment was over-reported in the medical records. The
      discriminatory power of the hospital mortality prediction model was significantly
      improved with the incorporation of functional status information but it was not
      significantly affected by their time reference or source of data.

PMID- 22583542
TI  - Surgery in pregnancy.

PMID- 22583539
TI  - Evaluation of a new pocket echoscopic device for focused cardiac ultrasonography
      in an emergency setting.
AB  - INTRODUCTION: In the emergency setting, focused cardiac ultrasound has become a
      fundamental tool for diagnostic, initial emergency treatment and triage
      decisions. A new ultra-miniaturized pocket ultrasound device (PUD) may be suited
      to this specific setting. Therefore, we aimed to compare the diagnostic ability
      of an ultra-miniaturized ultrasound device (VscanTM, GE Healthcare, Wauwatosa,
      WI) and of a conventional high-quality echocardiography system (Vivid S5TM, GE
      Healthcare) for a cardiac focused ultrasonography in patients admitted to the
      emergency department. METHODS: During 4 months, patients admitted to our
      emergency department and requiring transthoracic echocardiography (TTE) were
      included in this single-center, prospective and observational study. Patients
      underwent TTE using a PUD and a conventional echocardiography system. Each
      examination was performed independently by a physician experienced in
      echocardiography, unaware of the results found by the alternative device. During
      the focused cardiac echocardiography, the following parameters were assessed:
      global cardiac systolic function, identification of ventricular enlargement or
      hypertrophy, assessment for pericardial effusion and estimation of the size and
      the respiratory changes of the inferior vena cava (IVC) diameter. RESULTS: One
      hundred fifty-one (151) patients were analyzed. With the tested PUD, the image
      quality was sufficient to perform focused cardiac ultrasonography in all
      patients. Examination using PUD adequately qualified with a very good agreement
      global left ventricular systolic dysfunction (kappa = 0.87; 95%CI: 0.76-0.97),
      severe right ventricular dilation (kappa = 0.87; 95%CI: 0.71-1.00), inferior vena
      cava dilation (kappa = 0.90; 95%CI: 0.80-1.00), respiratory-induced variations in
      inferior vena cava size in spontaneous breathing (kappa = 0.84; 95%CI: 0.71
      0.98), pericardial effusion (kappa = 0.75; 95%CI: 0.55-0.95) and compressive
      pericardial effusion (kappa = 1.00; 95%CI: 1.00-1.00). CONCLUSIONS: In an
      emergency setting, this new ultraportable echoscope (PUD) was reliable for the
      real-time detection of focused cardiac abnormalities.

PMID- 22583544
TI  - Elderly suicide rates: the importance of a non-linear relationship with distal
      risk and protective factors.

PMID- 22583543
TI  - Efficient subtraction of insect rRNA prior to transcriptome analysis of Wolbachia
      Drosophila lateral gene transfer.
AB  - BACKGROUND: Numerous methods exist for enriching bacterial or mammalian mRNA
      prior to transcriptome experiments. Yet there persists a need for methods to
      enrich for mRNA in non-mammalian animal systems. For example, insects contain
      many important and interesting obligate intracellular bacteria, including
      endosymbionts and vector-borne pathogens. Such obligate intracellular bacteria
      are difficult to study by traditional methods. Therefore, genomics has greatly
      increased our understanding of these bacteria. Efficient subtraction methods are
      needed for removing both bacteria and insect rRNA in these systems to enable
      transcriptome-based studies. FINDINGS: A method is described that efficiently
      removes >95% of insect rRNA from total RNA samples, as determined by
      microfluidics and transcriptome sequencing. This subtraction yielded a 6.2-fold
      increase in mRNA abundance. Such a host rRNA-depletion strategy, in combination
      with bacterial rRNA depletion, is necessary to analyze transcription of obligate
      intracellular bacteria. Here, transcripts were identified that arise from a
      lateral gene transfer of an entire Wolbachia bacterial genome into a Drosophila
      ananassae chromosome. In this case, an rRNA depletion strategy is preferred over
      polyA-based enrichment since transcripts arising from bacteria-to-animal lateral
      gene transfer may not be poly-adenylated. CONCLUSIONS: This enrichment method
      yields a significant increase in mRNA abundance when poly-A selection is not
      suitable. It can be used in combination with bacterial rRNA subtraction to enable
      experiments to simultaneously measure bacteria and insect mRNA in vector and
      endosymbiont biology experiments.

PMID- 22583545
TI  - The single center registry for therapeutic apheresis in Turkey: 11-year activity.
AB  - Therapeutic apheresis (TA) is used as primary and adjunctive therapy in the
      treatment of several diseases and syndromes. We retrospectively evaluated the
      results of therapeutic apheresis (TA) including therapeutic plasma-exchange
      (TPE), double filtration plasmapheresis (DFPP), therapeutic thrombocytapheresis
      and leukocytapheresis as 11-year activity during 2000-2011. A total of 845 TA
      procedures were performed in 114 patients (67 male and 47 female, with mean age
      51+/-17 years). Adverse events (AE) were seen in 8.6% of procedures. None of the
      patients died from any complication. TA is safely carried out in our center in
      several diseases which are similar to previous reports.

PMID- 22583546
TI  - Responses of leaf nitrogen and mobile carbohydrates in different Quercus
      species/provenances to moderate climate changes.
AB  - Global warming and shortage of water have been evidenced in the recent past and
      are predicted for the future. Climate change will inevitably have considerable
      impact on plant physiology, growth, productivity and forest ecosystem functions.
      The present study determined the effects of simulated daytime air warming (+1 to
      1.5  degrees C during the growing season), drought (-40% and -57% of mean
      precipitation of 728 mm during the 2007 and 2008 growing season, respectively)
      and their combination, on leaf nitrogen (N) and non-structural carbohydrates
      (NSC) of two Quercus species (Q. robur and Q. petraea) and provenances (two
      provenances for each species) grown in two soil types in Switzerland across two
      treatment years, to test the hypothesis that leaf N and NSC in the more water
      sensitive species (Q. robur) and provenances (originating from water-rich
      locations) will more strongly respond to global warming and water deficit,
      compared to those in the more drought-tolerant species (Q. petraea) or
      provenances. No species- and provenance-specific responses in leaf N and NSC to
      the climate treatment were found, indicating that the results failed to support
      our hypothesis. The between-species variation of leaf N and NSC concentrations
      mainly reflected differences in biology of the two species, and the between
      provenance variation of N and NSC concentrations apparently mirrored the climate
      of their origins. Hence, we conclude that (i) the two Quercus species studied are
      somewhat insensitive, due to their distribution covering a wide geographical and
      climate range, to moderate climate change within Switzerland, and (ii) a moderate
      global warming of B1 scenario (IPCC 2007) will not, or at least less, negatively
      affect the N and carbon physiology in Q. robur and Q. petraea.

PMID- 22583547
TI  - Antimicrobial activity of Sesbania grandiflora flower polyphenol extracts on some
      pathogenic bacteria and growth stimulatory effect on the probiotic organism
      Lactobacillus acidophilus.
AB  - Polyphenolic extracts (PE) of edible flower of Sesbania grandiflora were tested
      to evaluate its antimicrobial effect against some common pathogenic bacteria and
      growth promoting property against probiotic organism Lactobacillus acidophilus.
      The antimicrobial activity of S. grandiflora flower PE against selected pathogens
      was evaluated using both in vitro and in situ methods. In vitro studies suggested
      that PE has inhibitory effect against Staphylococcus aureus, Shigella flexneri
      2a, Salmonella Typhi, Escherichia coli and Vibrio cholerae. The gram-positive
      organism S. aureus was the most sensitive organism to PE and minimum inhibitory
      concentration (MIC) was found to be 0.013 mg/mL where as the MIC of PE against V.
      cholerae was the highest (0.25 mg/mL). On the other hand PE showed growth
      promoting effect on the common probiotic bacterium L. acidophilus. The major
      finding was that S. grandiflora PE induced a significant biomass increase of L.
      acidophilus grown in liquid culture media. PE showed reduction of S. aureus
      growth in food (fish) during storage at 10 degrees C. High performance liquid
      chromatography analysis showed that rutin, a major flavonoid of the PE diminished
      in the culture medium MRS broth with the growth of L. acidophilus.

PMID- 22583548
TI  - Treatment of burns in the first 24 hours: simple and practical guide by answering
      10 questions in a step-by-step form.
AB  - Residents in training, medical students and other staff in surgical sector,
      emergency room (ER) and intensive care unit (ICU) or Burn Unit face a multitude
      of questions regarding burn care. Treatment of burns is not always
      straightforward. Furthermore, National and International guidelines differ from
      one region to another. On one hand, it is important to understand
      pathophysiology, classification of burns, surgical treatment, and the latest
      updates in burn science. On the other hand, the clinical situation for treating
      these cases needs clear guidelines to cover every single aspect during the
      treatment procedure. Thus, 10 questions have been organised and discussed in a
      step-by-step form in order to achieve the excellence of education and the optimal
      treatment of burn injuries in the first 24 hours. These 10 questions will clearly
      discuss referral criteria to the burn unit, primary and secondary survey,
      estimation of the total burned surface area (%TBSA) and the degree of burns as
      well as resuscitation process, routine interventions, laboratory tests,
      indications of Bronchoscopy and special considerations for Inhalation trauma,
      immediate consultations and referrals, emergency surgery and admission orders.
      Understanding and answering the 10 questions will not only cover the management
      process of Burns during the first 24 hours but also seems to be an interactive
      clear guide for education purpose.

PMID- 22583549
TI  - Upregulation of SATB1 promotes tumor growth and metastasis in liver cancer.
AB  - BACKGROUND: Special AT-rich binding protein-1 (SATB1) reprograms chromatin
      organization and transcription profiles to promote tumour growth and metastasis.
      AIMS: This study aimed to confirm the effects of SATB1 on the growth and
      metastasis of liver cancer and its specific regulation mechanism. METHODS: SATB1
      expression was evaluated in human hepatoma tissue, adjacent noncancerous tissue
      and seven kinds of liver cancer cell lines. Cell cycle, cell proliferation,
      apoptosis and epithelial-mesenchymal transition (EMT) was investigated after
      enhanced or silenced expression of SATB1. The regulatory action of SATB1 on the
      expression of genes that are known to regulate cell cycle progression, apoptosis
      and EMT and the specific apoptotic pathway on which it acts were further
      analysed. Nude mice that received subcutaneous implantation were used to study
      the effects of SATB1 on tumour growth in vivo. RESULTS: Our data show that the
      high expression of SATB1 was observed in the human hepatocellular carcinoma
      tissue (26/45) and liver cancer cell lines with high metastatic potential. SATB1
      upregulated CDK4 and downregulated p16 (INK) (4A) to promote cell cycle
      progression and cell proliferation and prevented apoptosis by inhibiting the FADD
      caspase-8-caspase-3 death receptor-mediated apoptosis pathway. SATB1 also induced
      EMT concomitant with increased expression of Snail1, Slug, Twist and vimentin and
      decreased expression of E-cadherin, tight junction protein ZO-1 and desmoplakin.
      SATB1 promoted the growth of tumour in vivo. CONCLUSION: These data suggest that
      the SATB1 gene may play an important role in the development and progression of
      liver cancer by regulation of genes related to cell cycle progression, apoptosis
      and EMT.

PMID- 22583550
TI  - Consequences of severe visual-spatial deficits for reading acquisition: evidence
      from Williams syndrome.
AB  - To further understand the nature of the visual-spatial representations required
      for successful acquisition of written language skills, we investigated the
      written language abilities of two individuals with Williams syndrome (WS) a
      developmental genetic disorder in which the presence of severe visual-spatial
      developmental delays and deficits has been well established. Using a case study
      approach, we examined the relationship between reading achievement and general
      cognitive ability, phonological skills, and visual-spatial skills for the two
      individuals. We found that, despite the strong similarity between the two
      individuals in terms of their verbal and non-verbal cognitive abilities and their
      phonological abilities (as well as chronological age and educational
      opportunities), their reading and spelling abilities differed by more than 5
      grade levels. We present evidence that the difference in written language
      performance was likely to be due to differences in the severity and nature of
      their visual-spatial impairment. Moreover, we show that specific difficulty
      processing the orientation of visual stimuli is related to the reading
      difficulties of one of the two individuals. These results underscore the
      contribution of visual-spatial abilities to the reading acquisition process and
      identify WS as a potential source of valuable information regarding the role of
      visual-spatial processing in reading development. 

PMID- 22583551
TI  - Prevention and treatment of surgical site infection in HIV-infected patients.
AB  - BACKGROUND: Surgical site infection (SSI) are the third most frequently reported
      nosocomial infection, and the most common on surgical wards. HIV-infected
      patients may increase the possibility of developing SSI after surgery. There are
      few reported date on incidence and the preventive measures of SSI in HIV-infected
      patients. This study was to determine the incidence and the associated risk
      factors for SSI in HIV-infected patients. And we also explored the preventive
      measures. METHODS: A retrospective study of SSI was conducted in 242 HIV-infected
      patients including 17 patients who combined with hemophilia from October 2008 to
      September 2011 in Shanghai Public Health Clinical Center. SSI were classified
      according to Centers for Disease Control and Prevention (CDC) criteria and
      identified by bedside surveillance and post-discharge follow-up. Data were
      analyzed using SPSS 16.0 statistical software (SPSS Inc., Chicago, IL). RESULTS:
      The SSI incidence rate was 47.5% (115 of 242); 38.4% incisional SSIs, 5.4% deep
      incisional SSIs and 3.7% organ/space SSIs. The SSI incidence rate was 37.9% in
      HIV-infected patients undergoing abdominal operation. Patients undergoing
      abdominal surgery with lower preoperative CD4 counts were more likely to develop
      SSIs. The incidence increased from 2.6% in clean wounds to 100% in dirty wounds.
      In the HIV-infected patients combined with hemophilia, the mean preoperative
      albumin and postoperative hemoglobin were found significantly lower than those in
      no-SSIs group (P<0.05). CONCLUSIONS: SSI is frequent in HIV-infected patients.
      And suitable perioperative management may decrease the SSIs incidence rate of HIV
      infected patients.

PMID- 22583552
TI  - Measuring data reliability for preventive services in electronic medical records.
AB  - BACKGROUND: Improvements in the quality of health care services are often
      measured using data present in medical records. Electronic Medical Records (EMRs)
      contain potentially valuable new sources of health data. However, data quality in
      EMRs may not be optimal and should be assessed. Data reliability (are the same
      data elements being measured over time?) is a prerequisite for data validity (are
      the data accurate?). Our objective was to measure the reliability of data for
      preventive services in primary care EMRs during the transition to EMR. METHODS:
      Our data sources were randomly selected eligible patients' medical records and
      data obtained from provincial administrative datasets. Eighteen community-based
      family physicians in Toronto, Ontario that implemented EMRs starting in 2006
      participated in this study. We measured the proportion of patients eligible for a
      service (Pap smear, screening mammogram or influenza vaccination) that received
      the service. We compared the change in rates of selected preventive services
      calculated from the medical record audits with the change in administrative
      datasets. RESULTS: In the first year of EMR use (2006) services decreased by 8.7%
      more (95% CI -11.0%- - 6.4%, p < 0.0001) when measured through medical record
      audits as compared with administrative datasets. Services increased by 2.4% more
      (95% CI 0%-4.9%, p = 0.05) in the medical record audits during the second year of
      EMR use (2007). CONCLUSION: There were differences between the change measured
      through medical record audits and administrative datasets. Problems could include
      difficulties with organizing new data entry processes as well as continued use of
      both paper and EMRs. Data extracted from EMRs had limited reliability during the
      initial phase of EMR implementation. Unreliable data interferes with the ability
      to measure and improve health care quality.

PMID- 22583553
TI  - Content of antioxidative caffeoylquinic acid derivatives in field-grown Ligularia
      fischeri (Ledeb.) Turcz and responses to sunlight.
AB  - Ligularia fischeri (Ledeb.) Turcz, a commercial leafy vegetable, contains
      caffeoylquinic acid derivatives (CQAs) as major phenolic constituents. The HPLC
      chromatograms of leaf extracts collected from different areas in Korea showed a
      significant variation in CQA amount, and two tri-O-caffeoylquinic acids (triCQAs)
      were purified and structurally identified by NMR and MS from this plant. Radical
      scavenging activities among CQAs were found to be increased in proportion to the
      number of caffeoyl groups. Since this plant prefers damp and shady growth
      conditions, the effects of sunlight were investigated by growing plantlets in
      sunlight and shade for four weeks. Greater leaf thickness and higher phenolic
      contents were found for leaves grown in sunlight than in shade. Four major CQAs-5
      mono-O-caffeoylquinic acid (5-monoCQA), and 3,4-, 3,5-, and 4,5-di-O
      caffeoylquinic acid (diCQA)-were induced by solar irradiation, whereas the
      content of these compounds decreased steadily in shade leaves. The leaves of L.
      fischeri clearly showed adaptation responses to sunlight, and these
      characteristics can be exploited for cultivation of this plant for potential use
      as a nutraceutical and functional food.

PMID- 22583554
TI  - We are delighted to have received 273 replies from reviewers specifying their
      subspecialty interests. Introduction.

PMID- 22583555
TI  - Serum metabolomic profile as a means to distinguish stage of colorectal cancer.
AB  - BACKGROUND: Presently, colorectal cancer (CRC) is staged preoperatively by
      radiographic tests, and postoperatively by pathological evaluation of available
      surgical specimens. However, present staging methods do not accurately identify
      occult metastases. This has a direct effect on clinical management. Early
      identification of metastases isolated to the liver may enable surgical resection,
      whereas more disseminated disease may be best treated with palliative
      chemotherapy. METHODS: Sera from 103 patients with colorectal adenocarcinoma
      treated at the same tertiary cancer center were analyzed by proton nuclear
      magnetic resonance (1H NMR) spectroscopy and gas chromatography-mass spectroscopy
      (GC-MS). Metabolic profiling was done using both supervised pattern recognition
      and orthogonal partial least squares-discriminant analysis (O-PLS-DA) of the most
      significant metabolites, which enables comparison of the whole sample spectrum
      between groups. The metabolomic profiles generated from each platform were
      compared between the following groups: locoregional CRC (N = 42); liver-only
      metastases (N = 45); and extrahepatic metastases (N = 25). RESULTS: The serum
      metabolomic profile associated with locoregional CRC was distinct from that
      associated with liver-only metastases, based on 1H NMR spectroscopy (P = 5.10 *
      10-7) and GC-MS (P = 1.79 * 10-7). Similarly, the serum metabolomic profile
      differed significantly between patients with liver-only metastases and with
      extrahepatic metastases. The change in metabolomic profile was most markedly
      demonstrated on GC-MS (P = 4.75 * 10-5). CONCLUSIONS: In CRC, the serum
      metabolomic profile changes markedly with metastasis, and site of disease also
      appears to affect the pattern of circulating metabolites. This novel observation
      may have clinical utility in enhancing staging accuracy and selecting patients
      for surgical or medical management. Additional studies are required to determine
      the sensitivity of this approach to detect subtle or occult metastatic disease.

PMID- 22583556
TI  - Tuberculosis and alcohol misuse in Scotland: a population-based study using
      enhanced surveillance data.
AB  - OBJECTIVE: To identify for the first time in Scotland the epidemiological
      characteristics of tuberculosis (TB) patients who misuse alcohol. DESIGN: A
      retrospective cohort study using Enhanced Surveillance of Mycobacterial
      Infections (ESMI) scheme data for adult (aged >= 18 years) TB cases notified in
      Scotland, 2001-2007. Characteristics and treatment outcomes of TB cases with and
      without recorded alcohol misuse were compared. RESULTS: Of 2419 adult TB cases,
      alcohol misuse was recorded in 426 (18%). Alcohol misuse was associated with male
      sex, White ethnicity, birth in the United Kingdom, unemployment, urban residence
      and socio-economic deprivation. Alcohol misusers were more likely than other TB
      cases to have pulmonary TB (92% vs. 61%, P < 0.001), be sputum smear-positive
      (74% vs. 58%, P < 0.001) and be enrolled on directly observed treatment (30% vs.
      3%, P < 0.001). Treatment completion rates were respectively 77% and 79% (P =
      0.34) in alcohol misusers and other TB cases. CONCLUSION: We have identified
      epidemiological characteristics associated with alcohol misuse among TB patients
      in Scotland, notably socio-economic deprivation. We suggest improvements in data
      collection to allow more robust findings to inform policy decisions to assist the
      prevention and management of alcohol misuse and reduce the TB incidence in
      Scotland.

PMID- 22583557
TI  - How a calculated oxidative stress can yield multiple therapeutic effects.
AB  - It is proposed to discuss how ozonetherapy acts on patients affected by vascular
      and degenerative diseases. Ozone is a strong oxidant but, if used in small
      dosages on human blood ex vivo, acts as an acceptable stressor. By instantly
      reacting with PUFA bound to albumin, ozone is entirely consumed but generates two
      messengers acting in an early and in a late phase: the former is due to hydrogen
      peroxide, which triggers biochemical pathways on blood cells and the latter is
      due to alkenals which are infused into the donor patient. After undergoing a
      partial catabolism, alkenals enter into a great number of body's cells, where
      they react with Nrf2-Keap1 protein: the transfer of activated Nrf2 into the
      nucleus and its binding to antioxidant response element (ARE) is the crucial
      event able to upregulate the synthesis of antioxidant proteins, phase II enzymes
      and HO-1. With the progress of ozonetherapy, these protective enzymes are able to
      reverse the oxidative stress induced by chronic inflammation. Consequently, the
      repetition of graduated stresses induces a multiform adaptive response able to
      block the progress of the disease and to improve the quality of life.

PMID- 22583559
TI  - How metabolic acidosis and oxidative stress alone and interacting may increase
      the risk of fracture in diabetic subjects.
AB  - Subjects with either type 1 or type 2 diabetes are at higher risk for having
      fractures, a risk not necessarily improved by better glucose control. In this
      article, we argue that low grade metabolic acidosis and increased oxidative
      stress occurring in bone disease in part as a result of complications of
      diabetes, reinforce each other, and together constitute a double jeopardy for the
      development of bone fractures in diabetic subjects.

PMID- 22583558
TI  - Exploration of multivariate analysis in microbial coding sequence modeling.
AB  - BACKGROUND: Gene finding is a complicated procedure that encapsulates algorithms
      for coding sequence modeling, identification of promoter regions, issues
      concerning overlapping genes and more. In the present study we focus on coding
      sequence modeling algorithms; that is, algorithms for identification and
      prediction of the actual coding sequences from genomic DNA. In this respect, we
      promote a novel multivariate method known as Canonical Powered Partial Least
      Squares (CPPLS) as an alternative to the commonly used Interpolated Markov model
      (IMM). Comparisons between the methods were performed on DNA, codon and protein
      sequences with highly conserved genes taken from several species with different
      genomic properties. RESULTS: The multivariate CPPLS approach classified coding
      sequence substantially better than the commonly used IMM on the same set of
      sequences. We also found that the use of CPPLS with codon representation gave
      significantly better classification results than both IMM with protein (p <
      0.001) and with DNA (p < 0.001). Further, although the mean performance was
      similar, the variation of CPPLS performance on codon representation was
      significantly smaller than for IMM (p < 0.001). CONCLUSIONS: The performance of
      coding sequence modeling can be substantially improved by using an algorithm
      based on the multivariate CPPLS method applied to codon or DNA frequencies.

PMID- 22583560
TI  - The world epidemic of sleep disorders is linked to vitamin D deficiency.
AB  - An observation of sleep improvement with vitamin D supplementation led to a 2
      year uncontrolled trial of vitamin D supplementation in 1500 patients with
      neurologic complaints who also had evidence of abnormal sleep. Most patients had
      improvement in neurologic symptoms and sleep but only through maintaining a
      narrow range of 25(OH) vitamin D3 blood levels of 60-80 ng/ml. Comparisons of
      brain regions associated with sleep-wake regulation and vitamin D target neurons
      in the diencephalon and several brainstem nuclei suggest direct central effects
      of vitamin D on sleep. We propose the hypothesis that sleep disorders have become
      epidemic because of widespread vitamin D deficiency. The therapeutic effects
      together with the anatomic-functional correspondence warrant further
      investigation and consideration of vitamin D in the etiology and therapy of sleep
      disorders.

PMID- 22583561
TI  - Diacerein: a potential therapeutic drug for periodontal disease.
AB  - Periodontal diseases are chronic inflammatory diseases characterized by the
      destruction of the tooth-supporting structures. They are the most prevalent form
      of bone pathology in humans and act as a modifying factor of the systemic health
      of patients. Accumulating evidence has provided insight into mechanisms of
      periodontal inflammation revealing that oral pathogens induce inflammatory
      cascades, including a variety of cytokines produced by different cell types,
      which promotes host-mediated tissue destruction. Cytokine networks established in
      diseased periodontal tissues are extremely complex, and substances regulating
      immuno-inflammatory reactions and signaling pathways, in addition to traditional
      periodontal treatment, could potentially be targeted as an approach for
      prevention and treatment of periodontal diseases. Diacerein, a purified
      anthraquinone derivative, was derived originally from plants with profound anti
      inflammatory and analgesic activities. Its wide range of biological activities
      have been applied and discussed for several decades; however, studies of
      diacerein have mainly concentrated on effects on joint-derived tissues/cells,
      which suggest a beneficial role in osteoarthritis treatment. Diacerein reduces
      association of the IL-1 receptor to form heterodimer complexes, repressing IL-1
      and its related downstream events and impairing active IL-1 release due to the
      inhibition of the IL-1-converting enzyme (ICE). To date, there are no reports
      describing the therapeutic effect of diacerein for treatment of periodontitis.
      Given the involvement of inflammation and occurrence of tissue destruction in
      periodontal disease, we propose that diacerein might be a promising biological
      drug for periodontal disease due to its therapeutic advantages. In addition, we
      hypothesize that the underlying mechanisms might involve the capacity of
      diacerein to selectively inhibit signal transduction to affect the cytokine
      profiles and, consequently, produce the outcome of ameliorating disease
      breakdown.

PMID- 22583562
TI  - Comparison of the burden of illness for adults with ADHD across seven countries:
      a qualitative study.
AB  - BACKGROUND: The purpose of this study was to expand the understanding of the
      burden of illness experienced by adults with Attention Deficit-Hyperactivity
      Disorder (ADHD) living in different countries and treated through different
      health care systems. METHODS: Fourteen focus groups and five telephone interviews
      were conducted in seven countries in North America and Europe, comprised of
      adults who had received a diagnosis of ADHD. The countries included Canada,
      France, Germany, Italy, The Netherlands, United Kingdom, and United States (two
      focus groups in each country). There were 108 participants. The focus groups were
      designed to elicit narratives of the experience of ADHD in key domains of
      symptoms, daily life, and social relationships. Consonant with grounded theory,
      the transcripts were analyzed using descriptive coding and then themed into
      larger domains. RESULTS: Participants' statements regarding the presentation of
      symptoms, childhood experience, impact of ADHD across the life course, addictive
      and risk-taking behavior, work and productivity, finances, relationships and
      psychological health impacts were similarly themed across all seven countries.
      These similarities were expressed through the domains of symptom presentation,
      childhood experience, medication treatment issues, impacts in adult life and
      across the life cycle, addictive and risk-taking behavior, work and productivity,
      finances, psychological and social impacts. CONCLUSIONS: These data suggest that
      symptoms associated with adult ADHD affect individuals similarly in different
      countries and that the relevance of the diagnostic category for adults is not
      necessarily limited to certain countries and sociocultural milieus.

PMID- 22583564
TI  - Adult congenital heart disease interventions: recommendations from a joint
      working group of the British Congenital Cardiac Association, British
      Cardiovascular Intervention Society, and the British Cardiovascular Society.
AB  - In order to optimise care of the adult patients with complex congenital heart
      disease, there is a need to develop recommendations for interventions. This
      document is the work of representatives of the three relevant societies and
      provides recommendations for institutions and operators performing cardiac
      interventions in these patients.

PMID- 22583563
TI  - Genetic and environmental predictors of serum 25-hydroxyvitamin D concentrations
      among middle-aged and elderly Chinese in Singapore.
AB  - Vitamin D is known for maintaining Ca homeostasis and bone structure, and may
      also decrease susceptibility to chronic and infectious diseases. However, data on
      vitamin D status and its predictors among Southeast Asian populations are
      limited. We evaluated the distribution and determinants (genetic and
      environmental) of serum 25-hydroxyvitamin D (25(OH)D) concentrations among 504
      middle-aged and elderly participants (aged 45-74 years) in the Singapore Chinese
      Health Study. Data on dietary and other lifestyle factors were collected by
      trained interviewers. Serum 25(OH)D concentrations and genetic polymorphisms in
      vitamin D metabolism pathway enzymes (cytochrome P450 (CYP) 2R1, 3A4, 27B1, 24A1;
      vitamin D binding protein (also known as group-specific component, GC); and
      vitamin D receptor) were measured using stored biospecimens. Mean 25(OH)D
      concentration was 68.8 nmol/l. Serum 25(OH)D concentrations were positively
      associated with dietary vitamin D intake, and inversely associated with hours
      spent sitting at work. BMI was not associated with 25(OH)D concentrations. CYP2R1
      rs10741657, rs12794714, rs1993116; CYP3A4 rs2242480; and GC rs4588, rs7041,
      rs16847015, rs2298849 were statistically significantly associated with 25(OH)D
      concentrations. Individuals with the Gc2-2 haplotype (rs4588AA/rs7041TT) had
      statistically significantly lower 25(OH)D concentrations compared to all other Gc
      haplotypes (P-trend < 0.001). The majority of participants (86 %) had 25(OH)D
      concentrations >= 50 nmol/l, which is consistent with the 2011 Institute of
      Medicine (US) recommendation for bone health, and 32 % had concentrations of >=
      75 nmol/l that are thought to be required for broader health effects. Dietary
      vitamin D intake, hours spent indoors at work and genetic variation in CYP2R1,
      CYP3A4 and GC are significant predictors of 25(OH)D concentrations among
      Singapore Chinese.

PMID- 22583565
TI  - Natural antimicrobial peptides from bacteria: characteristics and potential
      applications to fight against antibiotic resistance.
AB  - Because of the emergence of antibiotic-resistant pathogens worldwide, a number of
      infectious diseases have become difficult to treat. This threatening situation is
      worsened by the fact that very limited progress has been made in developing new
      and potent antibiotics in recent years. However, a group of antimicrobials, the
      so-called bacteriocins, have been much studied lately because they hold a great
      potential in controlling antibiotic-resistant pathogens. Bacteriocins are small
      antimicrobial peptides (AMPs) produced by numerous bacteria. They often act
      toward species related to the producer with a very high potency (at pico- to
      nanomolar concentration) and specificity. The common mechanisms of killing by
      bacteriocins are destruction of target cells by pore formation and/or inhibition
      of cell wall synthesis. Several studies have revealed that bacteriocins display
      great potential in the medical sector as bacteriocinogenic probiotics and in the
      clinic as therapeutic agents. In this review, we discuss the emerging antibiotic
      resistance and strategies to control its dissemination, before we highlight the
      potential of AMPs from bacteria as a new genre of antimicrobial agents.

PMID- 22583566
TI  - Evaluation and use of surveillance system data toward the identification of high
      risk areas for potential cholera vaccination: a case study from Niger.
AB  - BACKGROUND: In 2008, Africa accounted for 94% of the cholera cases reported
      worldwide. Although the World Health Organization currently recommends the oral
      cholera vaccine in endemic areas for high-risk populations, its use in Sub
      Saharan Africa has been limited. Here, we provide the principal results of an
      evaluation of the cholera surveillance system in the region of Maradi in Niger
      and an analysis of its data towards identifying high-risk areas for cholera.
      RESULTS: We evaluated the cholera surveillance data using a standard CDC
      protocol, through interviews with heads of the system, and a review of cholera
      data collected between 2006-2009. The surveillance system was found to be
      sufficiently reliable to be able to utilize the data for the detection of high
      risk areas for cholera vaccination. Temporal, geographic and socio-demographic
      analyses of cholera cases indicated that between 2006 and 2009, 433 cholera cases
      were reported in the Maradi region of Niger. Two deprived neighborhoods of the
      region's capital city, Bagalam and Yandaka, represented 1% of the regional
      population and 21% of the cholera cases, reaching a yearly incidence rate of 3
      per 1000 in 2006 and 2008, respectively. CONCLUSIONS: The results of this
      evaluation suggest that the reporting sensitivity of the surveillance system is
      sufficient, to appropriately classify the region as cholera endemic.
      Additionally, two overcrowded neighborhoods in the regional capital met WHO
      criteria for consideration for cholera vaccination.

PMID- 22583567
TI  - Mental health nurses' perceptions of good work in an acute setting.
AB  - Frequently, research and conference papers explore difficult or problematic areas
      of practice that can inadvertently render daily nursing accomplishments invisible
      and create the perception of a discipline in crisis. In this qualitative study,
      we explore the views of registered nurses about achievements in the workplace and
      good nursing work in an acute inpatient mental health setting in Sydney,
      Australia. Mental health nurses were asked a series of questions about their
      experiences and understanding of what constitutes good nursing work as well as
      their sense of optimism about their work. A total of 40 structured face-to-face
      interviews were completed. Among the responses to questions about achievements
      and good nursing practice, five broad themes were identified: i) teamwork; (ii)
      interpersonal interactions with patients; (iii) providing practical and holistic
      support to patients; (iv) patients' mental health improvements; and (v) optimism
      pessimism continuum. Findings contribute to a discussion of good nursing work in
      acute mental health settings, as well as self-perceptions of optimism and
      hopefulness, which are important contributors to positive, supportive health-care
      settings and patient recovery.

PMID- 22583568
TI  - The multiple market-exposure of waste management companies: a case study of two
      Swedish municipally owned companies.
AB  - This paper describes how the business model of two leading Swedish municipally
      owned solid waste management companies exposes them to four different but related
      markets: a political market in which their legitimacy as an organization is
      determined; a waste-as-material market that determines their access to waste as a
      process input; a technical market in which these companies choose what waste
      processing technique to use; and a commercial market in which they market their
      products. Each of these markets has a logic of its own. Managing these logics and
      articulating the interrelationships between these markets is a key strategic
      challenge for these companies.

PMID- 22583569
TI  - Participatory approach, acceptability and transparency of waste management LCAs:
      case studies of Torino and Cuneo.
AB  - The paper summarises the main results obtained from two extensive applications of
      Life Cycle Assessment (LCA) to the integrated municipal solid waste management
      systems of Torino and Cuneo Districts in northern Italy. Scenarios with
      substantial differences in terms of amount of waste, percentage of separate
      collection and options for the disposal of residual waste are used to discuss the
      credibility and acceptability of the LCA results, which are adversely affected by
      the large influence of methodological assumptions and the local socio-economic
      constraints. The use of site-specific data on full scale waste treatment
      facilities and the adoption of a participatory approach for the definition of the
      most sensible LCA assumptions are used to assist local public administrators and
      stakeholders showing them that LCA can be operational to waste management at
      local scale.

PMID- 22583570
TI  - Equine pericardial roll graft replacement of infected pseudoaneurysm of the
      aortic arch.
AB  - Resection of the infected aorta, debridement of the surrounding tissue, in situ
      graft replacement, and omentopexy is the standard procedure for treating infected
      aortic aneurysms, but the question of which graft material is optimal is still a
      matter of controversy. We recently treated a patient with an infected thoracic
      aortic aneurysm. The aneurysm was located in the proximal aortic arch. Because
      the patients had previously undergone abdominal surgery, the aortic arch were
      replaced in situ with a branched equine pericardial roll grafts. The patient is
      alive and well 23 months after the operation.

PMID- 22583571
TI  - Vascular-targeted photothermal therapy of an orthotopic murine glioma model.
AB  - AIM: To develop nanoshells for vascular-targeted photothermal therapy of glioma.
      MATERIALS & METHODS: The ability of nanoshells conjugated to VEGF and/or
      poly(ethylene glycol) (PEG) to thermally ablate VEGF receptor-2-positive
      endothelial cells upon near-infrared laser irradiation was evaluated in vitro.
      Subsequent in vivo studies evaluated therapy in mice bearing intracerebral glioma
      tumors by exposing tumors to near-infrared light after systemically delivering
      saline, PEG-coated nanoshells, or VEGF-coated nanoshells. The treatment effect
      was monitored with intravital microscopy and histology. RESULTS: VEGF-coated but
      not PEG-coated nanoshells bound VEGF receptor-2-positive cells in vitro to enable
      targeted photothermal ablation. In vivo, VEGF targeting doubled the proportion of
      nanoshells bound to tumor vessels and vasculature was disrupted following laser
      exposure. Vessels were not disrupted in mice that received saline. The normal
      brain was unharmed in all treatment and control mice. CONCLUSION: Nanoshell
      therapy can induce vascular disruption in glioma.

PMID- 22583572
TI  - Silver nanoparticles do not influence stem cell differentiation but cause minimal
      toxicity.
AB  - AIMS: To evaluate the toxicity and cellular uptake of both undifferentiated and
      differentiated human adipose-derived stem cells (hASCs) exposed to silver
      nanoparticles (Ag-NPs), and to assess their effect on hASC differentiation.
      MATERIALS & METHODS: hASC were exposed to 10- or 20-nm Ag-NPs at concentrations
      of 0.1, 1.0, 10.0, 50.0 and 100.0 ug/ml either before or after differentiation
      down the adipogenic or osteogenic pathways. RESULTS: Exposure of hASC to either
      10- or 20-nm Ag-NPs resulted in no significant cytotoxicity to hASC, and minimal
      dose-dependent toxicity to adipogenic and osteogenic cells at 10 ug/ml. Each of
      the hASC, adipogenic and osteogenic cells showed cellular uptake of both 10- and
      20-nm Ag-NPs, without causing significant ultrastructural alterations. Exposure
      to 10- or 20-nm Ag-NPs did not influence the differentiation of the cells, and at
      antimicrobial concentrations of Ag-NPs resulted in a minimal decrease in
      viability. CONCLUSION: The biocompatibility of Ag-NPs with both undifferentiated
      and differentiated hASC establishes their suitability for incorporation into
      tissue-engineered graft scaffolds, for the prevention of bacterial contamination
      upon implantation.

PMID- 22583573
TI  - Development of screening assays for nanoparticle toxicity assessment in human
      blood: preliminary studies with charged Au nanoparticles.
AB  - As nanoparticles have found increased use in both consumer and medical
      applications, corresponding increases in possible exposure to humans necessitate
      studies examining the impacts of these nanomaterials in biological systems. This
      article examines the effects of approximately 30-nm-diameter gold nanoparticles,
      with positively and negatively charged surface coatings in human blood. Here, we
      study the exposure effects, with up to 72 h of exposure to 5, 15, 25 and 50 ug/ml
      nanoparticles on hemolysis, reactive oxygen species (ROS) generation and platelet
      aggregation in subsets of cells from human blood. Assessing viability with
      hemolysis, results show significant changes in a concentration-dependent fashion.
      Rates of ROS generation were investigated using the dichlorofluorscein diacetate
      based assay as ROS generation is a commonly suspected mechanism of nanoparticle
      toxicity; herein, ROS was not a significant factor. Optical monitoring of
      platelet aggregation revealed that none of the examined nanoparticles induced
      aggregation upon short-term exposure.

PMID- 22583575
TI  - Modification of plasmid DNA topology by 'histone-mimetic' gold nanoparticles.
AB  - AIMS: Our aim is to explore whether gold nanoparticles (AuNPs) functionalized
      with a carboxylated polyethylene glycol (PEG) and protamine (AuNP@PEG@Prot) can
      modulate - enhance or restrain - DNA condensation, altering DNA conformation and
      inducing structural changes. Understanding how these nanoconjugates modulate DNA
      structure, size and shape of DNA condensates, and enable control over the
      resulting 3D structures is of major biological and therapeutic importance.
      MATERIALS & METHODS: Citrate-AuNPs were covered with a dense layer of a hetero
      functional octa(ethylene glycol) (SH-EG(8)-COOH). Conjugation of protamine to the
      AuNP@PEG was achieved by taking advantage of the carboxylated surface previously
      generated on the surface of the NP and the remaining amino groups from the
      protamine, using carbodiimide and N-hydroxysulfosuccinimide coupling reactions.
      RESULTS & CONCLUSION: AuNP@PEG@Prot modulates the structure and topology of DNA,
      not only for condensation, but also for decondensation, via formation of higher
      quantities of dimers and multimers, when compared with AuNP@PEG and free
      protamine.

PMID- 22583576
TI  - Folate-decorated PLGA nanoparticles as a rationally designed vehicle for the oral
      delivery of insulin.
AB  - AIMS: The present study reports a novel approach for enhancing the oral
      absorption and hypoglycemic activity of insulin via encapsulation in folate-(FA)
      coupled polyethylene glycol (PEG)ylated polylactide-co-glycolide (PLGA)
      nanoparticles (NPs; FA-PEG-PLGA NPs). MATERIALS & METHODS: Insulin-loaded FA-PEG
      PLGA NPs (size ~260 nm; insulin loading ~6.5% [w/w]; encapsulation efficiency:
      87.0 +/- 1.92%) were prepared by double-emulsion solvent evaporation method. The
      bioavailability and hypoglycemic activity of orally administered FA-insulin NPs
      were studied in diabetic rats. RESULTS & CONCLUSION: FA-PEG-PLGA NPs (50 U/kg)
      exhibited a twofold increase in the oral bioavailability (double hypoglycemia)
      without any hypoglycemic shock as compared to subcutaneously administered
      standard insulin solution. Insulin NPs maintained a continual blood glucose level
      for 24 h, which, however, was transient (<8 h) in the case of subcutaneous
      insulin and associated with severe hypoglycemic shock. Overall, we have developed
      a patient-compliant, oral nanoformulation of insulin, once-daily administration
      of which would be sufficient to control diabetes for at least 24 h.

PMID- 22583574
TI  - Prostate-targeted biodegradable nanoparticles loaded with androgen receptor
      silencing constructs eradicate xenograft tumors in mice.
AB  - BACKGROUND: Prostate cancer is the major cause of cancer death in men and the
      androgen receptor (AR) has been shown to play a critical role in the progression
      of the disease. Our previous reports showed that knocking down the expression of
      the AR gene using a siRNA-based approach in prostate cancer cells led to
      apoptotic cell death and xenograft tumor eradication. In this study, we utilized
      a biodegradable nanoparticle to deliver the therapeutic AR shRNA construct
      specifically to prostate cancer cells. MATERIALS & METHODS: The biodegradable
      nanoparticles were fabricated using a poly(dl-lactic-co-glycolic acid) polymer
      and the AR shRNA constructs were loaded inside the particles. The surface of the
      nanoparticles were then conjugated with prostate-specific membrane antigen
      aptamer A10 for prostate cancer cell-specific targeting. RESULTS: A10-conjugation
      largely enhanced cellular uptake of nanoparticles in both cell culture- and
      xenograft-based models. The efficacy of AR shRNA encapsulated in nanoparticles on
      AR gene silencing was confirmed in PC-3/AR-derived xenografts in nude mice. The
      therapeutic property of A10-conjugated AR shRNA-loaded nanoparticles was
      evaluated in xenograft models with different prostate cancer cell lines: 22RV1,
      LAPC-4 and LNCaP. Upon two injections of the AR shRNA-loaded nanoparticles, rapid
      tumor regression was observed over 2 weeks. Consistent with previous reports, A10
      aptamer conjugation significantly enhanced xenograft tumor regression compared
      with nonconjugated nanoparticles. DISCUSSION: These data demonstrated that tissue
      specific delivery of AR shRNA using a biodegradable nanoparticle approach
      represents a novel therapy for life-threatening prostate cancers.

PMID- 22583577
TI  - Drug metabolite heterogeneity in cultured single cells profiled by pico-trapping
      direct mass spectrometry.
AB  - AIM: We investigated the heterogeneity of tafluprost metabolism in primary human
      hepatocytes at a single-cell level by live single-cell mass spectrometry (MS).
      MATERIALS & METHODS: Picoliter volumes of cytoplasm were analyzed by nano
      electrospray ionization MS in order to obtain single-cell metabolite profiles.
      The subcellular components of a single tafluprost-treated human hepatocyte were
      isolated and the single-cell metabolite profile was compared with those of
      traditional bulk hepatocyte analysis. RESULTS: In the bulk hepatocyte analysis,
      liquid chromatography-MS showed the averaged metabolism of tafluprost to
      tafluprost acid (TA) and beta-oxidized metabolites. However, live single-cell MS
      showed that tafluprost metabolism varied among individual cells. In addition,
      there was significant variation in the quantities of TA and a major metabolite,
      dinor-TA, among cells, whereas there was no significant variation in 7
      ethoxycoumarin metabolism. CONCLUSION: Thus, live single-cell MS successfully
      detected the heterogeneity of drug metabolism in individual living hepatocytes.

PMID- 22583578
TI  - Risk-prediction tool for identifying hospitalized children with a predisposition
      for development of venous thromboembolism: Peds-Clot clinical Decision Rule.
AB  - BACKGROUND: The prevalence of VTE is increasing in tertiary pediatric hospitals.
      Identification of high-risk populations using uniform criteria is required to
      develop evidence-based VTE prevention guidelines. OBJECTIVE: To develop a VTE
      risk prediction rule, the Peds-Clot clinical Decision Rule (PCDR), to identify
      high-risk children who were at increased risk of developing VTE. METHODS: This
      retrospective case-control study developed the PCDR using a derivation cohort
      (173 cases, 346 controls) and validated it on a separate validation cohort (100
      cases, 100 controls). A uniform data collection strategy was applied to derive
      both the samples. Conditional logistic regression analyses were used to develop a
      risk-prediction model. Each significant predictor was assigned a score based on
      its beta coefficient and the PCDR was developed. ROC curves were derived to test
      the performance of the PCDR. RESULTS: Characteristics of derivation and
      validation cohorts were comparable. Six risk factors (positive blood stream
      infection, central venous catheter, direct admission to ICU/NICU, hospitalization
      for >= 7 days, immobilization for > 72 h, and use of birth control pills) formed
      the final risk prediction model (risk score range, 0.5-9.5). A risk score of 3 or
      more identified high-risk children at a sensitivity of 70% and specificity of 80%
      and AUC of 0.852 (95% confidence interval, 0.814-0.890). The application of a
      risk score to the validation sample showed sensitivity 57% and specificity 88%
      and an AUC of 0.875 (95% confidence interval, 0.82-0.924). CONCLUSION:
      Incorporation of the PCDR in routine clinical care can be an attractive strategy
      to identify high-risk hospitalized children with a predisposition for VTE. The
      clinical utility of the PCDR needs validation in prospective studies.

PMID- 22583579
TI  - Association between family doctors' practices characteristics and patient
      evaluation of care.
AB  - BACKGROUND: Patients' evaluations of primary care are influenced by three major
      dimensions: patients', family doctors' and practices' characteristics. A lot of
      primary care practices use possibilities of new information technologies, such as
      chronic patients' electronic registers, clinical guideline support systems,
      electronic medical records and clinical decision system. The aim of this study
      was to determine possible effects of quality characteristics of family doctors'
      practices on patients' satisfaction. METHODS: This observational cross-sectional
      study in 36 randomly selected family doctors' practices, stratified to practices'
      size and urbanization was performed between 2008 and 2009. Each practice included
      100 randomly selected adult patients: 30 high-risk patients for CVD, but without
      a history of CVD, 30 patients with an established coronary disease, and 40
      healthy adult patients (aged 18-45 years). Data was collected with a
      questionnaire, used in European Practice Assessment of Cardiovascular risk
      management (EPA Cardio study), and with European Patients Evaluation of general
      practice care (EUROPEP) questionnaire. RESULTS: Final sample consisted of 2482
      patients (68.9% response rate). Higher satisfaction scores were associated with
      worse self-rated patients' health status, with patients visiting practices where
      quality report was provided, where clinical audit in the past 12 months existed,
      where number of population attending practice quarterly was lower, where
      systematic reviewing of prescribed medication was not available, where annual
      report was not provided, where doctor did not have access to medical literature,
      and where patients' attendance rate for preventive check-ups was not available.
      Patients with higher risk for CVD were also more satisfied. CONCLUSION: The
      effect of practice characteristics associated with organisational access to
      services, chronic patients' management and some quality improvement factors is
      unclear and not always in favour of higher satisfaction score. Further studies
      are needed.

PMID- 22583580
TI  - A peaceful man.

PMID- 22583581
TI  - Effects of deflection and archwire dimension on the mechanical performance of two
      self-ligating orthodontic systems.
AB  - OBJECTIVES: To analyze the effects of archwire deflection and dimension on the
      mechanical performance of two self-ligating systems, as passive and active
      ligation designs. MATERIALS AND METHODS: An experimental model was used that was
      designed to resemble the full dental arch and to allow vertical displacement of a
      canine element. Two self-ligating systems were investigated: 1) a passive system;
      and 2) an active system, both in combination with three thermoactive NiTi
      archwires, with round sections of 0.014-in, 0.016-in and 0.018-in. The full
      loading-unloading cycles consisted of either 3mm or 6mm maximum deflection,
      performed at 37  degrees C. During unloading, the deactivation forces and energy
      were recorded. The ratio between the deactivation and activation energies was
      used as representative of the mechanical efficiencies of the systems. RESULTS:
      The deactivation force increased in combination with larger archwires and greater
      deflection. The deactivation energy increased in combination with larger
      archwires only for the 3-mm deflection cycle, while for the 6-mm deflection
      cycle, the deactivation energy was not influenced by the archwire dimension, and
      was not greater than that of the 3-mm deflection cycle. The mechanical efficiency
      decreased in combination with greater deflection and larger archwires, with a
      maximum decrease of about 12%. Only minor comparative differences were seen
      between the systems. CONCLUSIONS: The deflection degree and archwire dimension
      have large effects on the mechanical performance of self-ligating systems.

PMID- 22583582
TI  - In vitro evaluation of the effects of a fluoride-releasing composite on enamel
      demineralization around brackets.
AB  - OBJECTIVES: The aim of this in vitro study was to evaluate the effectiveness of a
      fluoride-releasing bonding agent in inhibiting enamel demineralization around
      orthodontic brackets after the exposure to a demineralizing solution. MATERIALS
      AND METHODS: Twenty-six extracted upper molars were bonded with two different
      composites: Transbond XT (TXT) and Transbond Plus (TPlus), fluoride-releasing
      (both 3M Unitek, Monrovia, CA, USA). The samples were exposed to an acid lactic
      solution for three days and then subjected to Metallographic Optical Microscope
      (MOM) and Scanning Electron Microscope/Energy Dispersive X-Ray (SEM/EDX)
      analyses. Enamel surface was examined in different areas: un-treated, etched and
      primer-painted, un-treated area with no acid exposure, central area with bracket
      bonded. The maximum demineralization depths and the fluoride content at 100, 200
      and 300 MUm depth were evaluated. RESULTS: MOM analysis showed statistically
      significant (p<0.001) differences in demineralization depth for TPlus group
      compared to TXT group with lower values for the first one. EDX analysis confirmed
      the presence of fluoride in TPlus group. CONCLUSIONS: The fluoride content of
      TPlus appeared able to weakly reduce the enamel demineralization.

PMID- 22583583
TI  - Early versus delayed rebonding of orthodontic brackets.
AB  - OBJECTIVES: There are controversial reports regarding the effect of repeated
      bonding on shear bond strength (SBS) of orthodontic attachments. The aim of this
      study was to evaluate the SBS of brackets following early and delayed rebonding,
      and after employing different methods of composite removal. MATERIALS AND
      METHODS: Sixty eight premolars were randomly assigned into 4 groups. After
      initial debonding and recording the SBS, the adhesive remnants in the first group
      were removed by a round bur, in the second group by a green rubber wheel, and in
      the third and fourth groups by 12-fluted tungsten carbide burs, all of them
      connecting to a low speed handpiece. In the fourth group following adhesive
      removal, the teeth were kept in a simulated oral environment for one month. Then,
      rebonding was performed and the second SBS was measured. Two representative
      samples from each group were examined under a scanning electron microscope
      following adhesive removal. The data were analyzed by ANOVA, Paired sample t-test
      and Chi-Square test. RESULTS: In the first group, the rebonding strength was
      decreased significantly (p<0.05), while composite removal with a tungsten carbide
      bur or a green rubber wheel did not affect SBS significantly (p>0.05). Late
      rebonding of brackets had no effect on the SBS (p>0.05). CONCLUSIONS: Postponing
      rebonding to the next visit does not improve the SBS significantly. It is
      recommended to use a tungsten carbide bur or a green rubber wheel, and not a
      round bur for removing adhesive remnants following debonding of orthodontic
      brackets.

PMID- 22583584
TI  - Bleaching effects on shear bond strengths of orthodontic brackets.
AB  - OBJECTIVES: The purpose of this research was to investigate the influence of 35%
      hydrogen peroxide on orthodontic bracket adhesion at zero hour, 24 hours, 7, 21
      and 56 days after dental bleaching. MATERIALS AND METHODS: Ninety bovine incisors
      were prepared for adhesion test and adhesive remnant index (ARI) determination.
      The 35% hydrogen peroxide was used as a bleaching agent and the Transbond XT as a
      bonding agent. RESULTS: Statiscally significant differences were observed between
      all the groups (p<0.001) and were observed in the comparison of zero hour and
      control group (p<0.001) and in the comparison of zero hour and 24 hours
      (p<0.001). ARI scores (0, 1, 2 e 3) also showed statiscally differences between
      all the groups (p=0.011) and at the comparison of all the test groups with the
      control: zero hour (p=0.001), 24 hours (p=0.009), 7 days (p=0.018), 21 days
      (p<0.001) e 56 days (p=0.004). CONCLUSIONS: The shear bond strength values became
      significantly lower when the bracket was bonded immediately after bleaching and
      quickly returned to control level in 24 hours. In seven days, there was a slight
      increase that was not significant and recovered to normal values in the next
      weeks. Different patterns of fractures were observed in bleached enamel when ARI
      scores were analyzed. The control group showed a high frequency of 3 score and
      none of zero score, the opposite behavior was observed in the test groups.

PMID- 22583585
TI  - Soft tissue, skeletal and dentoalveolar changes following conventional anchorage
      molar distalization therapy in class II non-growing subjects: a multicentric
      retrospective study.
AB  - OBJECTIVES: The purpose of this retrospective prolective study is to evaluate
      soft tissue, dentoalveolar and skeletal vertical changes following conventional
      anchorage molar distalization therapy in adult patients. MATERIALS AND METHODS:
      Forty-six patients (34 females, mean age 25 years 6 months; and 12 males, mean
      age 28 years 4 months) were recruited from 4 specialists Board Certified. All
      subjects underwent molar distalization therapy according different distalization
      mechanics. Cephalometric headfilms were available for all subjects before (T0)
      and at the end of comprehensive treatment (T1). The initial and final
      measurements and treatment changes were compared by means of a paired t-test or a
      paired Wilcoxon test. RESULTS: Mean total treatment time was 3 years 3 months +/-
      8 months. Maxillary first and second molars distalized 2.16+/-0.84 mm and 2.01+/
      0.69 mm respectively, but also maintained a slight distal tipping of 1.45 degrees
      (min 2.22 degrees , max -6.45 degrees ) and 3.35 degrees  (min 0.47 degrees ,
      max -15.48 degrees ) at the end of treatment. Distal movement of maxillary first
      molar contributed 57.6% to molar correction, and 42.4% was due to a mesial
      movement of mandibular first molar (1.59+/-0.46 mm). Dentoalveolar changes
      contributed to overjet correction; maxillary incisors retroclined 5.78 degrees +/
      3.17 degrees , lower incisors proclined 7.49 degrees +/-4.52 degrees  and
      occlusal plane rotated down and backward 2.32 degrees +/-2.10 degrees . A
      significant clockwise rotation of the mandible (1.97 degrees +/-1.32 degrees )
      and a significant increase in lower facial height (3.35+/-1.48) mm were observed.
      Upper lip slightly retruded (-1.76+/-1.70 mm) and lower lip protruded (0.96+/
      0.99 mm) but these changes had a negligible impact on clinical appearance.
      CONCLUSIONS: Although maxillary molar distalization therapy can be performed in
      adult patients, significant proclination of the lower incisors, clockwise
      rotation of the occlusal plane and increase in vertical facial dimension should
      be expected. Nevertheless, in absence of maxillary third molars and in presence
      of mandibular third molars this procedure could be recommended.

PMID- 22583586
TI  - A controlled study on diagnostic and prognostic measurements of palatally
      displaced canines on lateral cephalograms.
AB  - OBJECTIVES: The aim of this prospective controlled study was to determine the
      role that the lateral cephalogram can play in the detection of palatally
      displaced canines (PDCs). MATERIALS AND METHODS: The study was comprised of 85
      subjects in the late mixed dentition. Thirty-five subjects had PDCs (either
      unilateral or bilateral) identified on the panoramic radiograph (PDC group), and
      50 subjects presented with a normal pathway of upper permanent canine eruption as
      assessed on panoramic radiographs (No-PDC group). Linear and angular measurements
      on the lateral cephalograms concurrent with panoramic radiographs were compared
      between the PDC and No-PDC group statistically. RESULTS: All angular measurements
      that incorporated the main axis of the canine (to Frankfort horizontal, to the
      palatal plane, or to the axis of the central incisor) were significantly smaller
      in the PDC group (p<0.001). In terms of linear measurements, both the distance
      from the tip of the canine to the vertical axis of the central incisor parallel
      to Frankfort horizontal and the distance from the tip of the canine to the
      anterior alveolar ridge parallel to Frankfort horizontal showed significantly
      larger values in the PDC subjects than in normal controls. On the contrary, the
      vertical distance from the tip of the canine to the functional occlusal plane did
      not reveal any significant difference between the PDC and the No-PDC group.
      CONCLUSIONS: Early diagnosis of PDC is essential in order to avoid the occurrence
      of final canine impaction. If 3-D images of a displaced canine cannot be
      acquired, a lateral cephalogram can be a useful tool for the early detection of
      PDC in the late mixed dentition. The angle between the vertical axis of the
      canine and the palatal plane demonstrate diagnostic value when assessing PDCs.
      Values for this angle smaller than 102 degrees can indicate the presence of PDC.

PMID- 22583587
TI  - An in-vitro assessment of weekly cumulative fluoride release from three glass
      ionomer cements used for orthodontic banding.
AB  - OBJECTIVES: To compare the in-vitro Weekly Cumulative Fluoride Release (WCFR) of
      three Glass Ionomer Cements (GICs) used for orthodontic banding. MATERIALS AND
      METHODS: The GICs tested were Granitec (Confi-Dental, Louisville, CO, USA),
      Bandtite (American Orthodontics, Sheboygan, WI, USA) and Ariadent (Apadana Tak
      Co, Tehran, Iran). Fifteen discs of each GIC were constructed (6mm diameter and
      1.5mm depth). Specimens were immersed in 5 ml of deionised water and the WCFR was
      measured at weekly intervals, on days 1, 8, 15, 22 and 29 after immersion in
      deonised water, using the potentiometery device and single junction saturated
      calomel electrode technique (Jenway, England, UK). To compare the WCFR profile of
      3 GICS, data were subjected to the one-way analysis of variance (ANOVA), and were
      appropriate, the Scheffe or Tamhane multiple comparison tests (post-hoc). For
      assessing the longitudinal changes of average WCFRs in 3 GICs, the repeated
      measures ANOVA were used. Post hoc tests using the Bonferroni correction was also
      used to compare the average WCFRs at different time-points. RESULTS: One-way
      ANOVA and post-hoc multiple comparison tests revealed significant differences in
      WCFR among 3 GICs at five time-points (p<0.05). The post-hoc multiple comparison
      test revealed Bandtite cement had consistently higher WCFR at all time-points,
      compared to Granitec and Ariadent cements (p<0.05). The one-way ANOVA test
      revealed significant differences in WCFR at different time-points for all GIC
      groups (p<0.05). The day 8 exhibited the highest WCFR for all GICs. The repeated
      measures ANOVA test revealed significant differences in WCFR at different time
      points for all GIC groups (p<0.0005). Reviewing average WCFR on days 22 and 29,
      these values for Granitec, Bandtite and Ariadent GICs, were higher (p<0.05), not
      different (p>0.05), and significantly lower (p<0.05) than the day 1 values,
      respectively. CONCLUSIONS: Bandtite followed by Granitec showed higher WCFR
      compared to Ariadent.

PMID- 22583588
TI  - Myofunctional and speech rehabilitation after orthodontic-surgical treatment of
      dento-maxillofacial dysgnathia.
AB  - OBJECTIVES: The lingual dysfunctions play a considerable role in the pathogenesis
      of dentoskeletal dysmorphisms. The treatment of dento-maxillofacial dysgnathia
      implies a functional rehabilitation to re-harmonize the stomatognathic system.
      This study aims to demonstrate the importance of a rehabilitation protocol of
      functional orofacial parameters at the end of a surgical-orthodontic treatment in
      order to achieve long-term success. MATERIALS AND METHODS: After orthognathic
      surgery, facial expression exercises and jaw exercises are prescribed to promote
      the recovery of neuromuscular function. At the end of treatment, a sample of 30
      dysgnathic patients underwent a functional evaluation of the orofacial district
      to identify any lingual or articulatory dysfunctions. The information gathered
      led to an individual re-education program that consisted of an active
      myofunctional-logopedic approach integrated with appliances used as retention.
      RESULTS: 19 patients needed myofunctional therapy to re-educate deglutition and
      tongue posture. Articulatory disorders were found in 7 patients originally
      suffering from Class III and/or open-bite skeletal disharmony; 5 of these
      completed rehabilitation with speech therapy. After rehabilitation the functional
      parameters were completely normalized in 12 patients; in 5 cases, partial
      improvements were obtained, while in 2 cases the therapy was ineffective.
      CONCLUSIONS: In a patient undergoing post-surgical reconsolidation of his/her
      functional equilibrium even an uncontrolled speech defect may lead to an instable
      result. Only through an interdisciplinary approach it is possible to intercept
      and re-educate all the functions that are not compliant with the structural
      changes and to eliminate a tendency to relapse of the dysgnathia.

PMID- 22583589
TI  - Psychological aspects of orthodontics in clinical practice. Part two: general
      psychosocial wellbeing.
AB  - Orthodontists tend to treat/see their patients on a systematic, recurrent basis,
      often during crucial stages of psychological development. Therefore, they have a
      pivotal role in identifying a number of psychological as well as of psychiatric
      disorders. Effective communication is crucial and unfortunately, it is often
      underestimated in a busy clinical practice. Aim of part two of this article it to
      review the role clinical orthodontics and the orthodontist-patient relationship
      have on the patients' psychosocial wellbeing, including effects on self-esteem,
      bullying and harassment by peers, and even several psychiatric disorders, such as
      anorexia/bulimia nervosa, and attention deficit hyperactivity disorders. Due to
      the complexity and importance of these issues, the orthodontist may play a
      dynamic role, not only in the management of dental malocclusions, but at times,
      as "psychologist" and a counselor to the patient.

PMID- 22583590
TI  - Upper molar distalization on palatal miniscrews: an easy to manage palatal
      appliance.
AB  - Upper molar distalization supported by miniscrews has become increasingly popular
      in the last years. A detailed clinical and lab procedure for the realization of a
      distalization appliance (fast back or distal jet) connected to miniscrews
      inserted in the anterior region of the palate is presented. A case report
      illustrates the use of a fast back appliance supported by miniscrews to correct
      the mesial shift of the molars and of the premolars as a consequence of an early
      loss of the maxillary deciduous canines.

PMID- 22583591
TI  - Treatment of an upper impacted cuspid using ultrasonic surgery and a modified
      RPE. A case report.
AB  - This case report describes the possibility to use a modified rapid palatal
      expander like anchorage to reposition an included maxillary cuspid. Moreover it
      is enphasized the use of an ultrasonic device during surgery to expose the
      impacted tooth.

PMID- 22583592
TI  - Congenital macroglossia: surgical and orthodontic management.
AB  - OBJECTIVES: A case of congenital macroglossia is reported. The most important
      sign of macroglossia is tongue protrusion through the lips. Tongue protrusion
      might influence skeletal growth and can cause anterior open bite, proclination of
      upper and lower incisors and development of diastemas. MATERIALS AND METHODS: A 4
      year-old female patient was diagnosed with congenital macroglossia. Parents
      referred an abnormal tongue dimension since birth and the development of a
      progressive anterior open bite. The treatment of macroglossia included tongue
      reduction by partial glossectomy. She was seen regularly and at the age of eight
      years old a lingual frenectomy was performed and an orthodontic treatment was
      planned. RESULTS: At the end of the orthodontic treatment a Class I occlusion was
      obtained with correct overbite and overjet values. CONCLUSIONS: Early
      interception of macroglossia and surgical reduction in combination with
      orthodontic treatment can be seen as preventive measures to avoid the tongue
      influence on the development of malocclusions.

PMID- 22583593
TI  - Inhibitory effects of (-)-epigallocatechin-3-gallate and pterostilbene on
      pancreatic cancer growth in vitro.
AB  - BACKGROUND: It has been previously shown that the naturally occurring antioxidant
      (-)-epigallocatechin-3-gallate (EGCG), found in green tea, and pterostilbene, a
      stilbenoid derived from blueberries, inhibit pancreatic cancer in vitro when used
      individually. We hypothesized that the combination of EGCG and pterostilbene
      would reveal additive effects in vitro. METHODS: Using the pancreatic cancer cell
      lines MIA PaCa-2 and PANC-1, efficacy and synergism were evaluated for cell
      proliferation and viability (3-(4,5-dimethyltiazol-2-y1)-2,5-diphenltetrazolium
      bromide assays, cell cycle analysis) and mitochondrial apoptosis (mitochondrial
      depolarization, cytochrome C release, caspase-3/7 activity, cell death detection
      using enzyme-linked immunosorbent assay). RESULTS: Cell proliferation assays
      revealed significant additive antiproliferative effects with pterostilbene and
      EGCG in both cell lines at the later, 72-h, point (P < 0.05). MIA underwent S
      phase arrest with the combination (10-12% increase); however, cell cycle arrest
      was not observed in PANC. The combination induced mitochondrial depolarization
      and upregulated cytochrome C (P < 0.05) in MIA, but these effects were not
      observed in PANC. EGCG increased caspase-3/7 in MIA; however, the combination did
      not significantly increase the activity in either cell line (P < 0.05). Apoptosis
      was only observed in PANC (P < 0.05). The reduction in proliferation in MIA in
      the 3-(4,5-dimethyltiazol-2-y1)-2,5-diphenltetrazolium bromide assays with the
      combination indicated that cell death occurs, possibly through another mechanism.
      CONCLUSIONS: Our results are encouraging regarding the future use of EGCG and
      pterostilbene to improve traditional pancreatic cancer therapies. In conclusion,
      EGCG and pterostilbene have additive, antiproliferative effects in vitro and
      alter the apoptotic mechanisms in both cell lines by modulation at different
      points in the mechanism.

PMID- 22583594
TI  - Liver transplantation with donation after cardiac death donors: a comprehensive
      update.
AB  - BACKGROUND: Use of donation after cardiac death (DCD) donors has been proposed as
      an effective way to expand the availability of hepatic allografts used in
      orthotopic liver transplantation (OLT); yet, there remains no consensus in the
      medical literature as to how to choose optimal recipients and donors based on
      available information. METHODS: We queried the United Network of Organ
      Sharing/Organ Procurement and Transplantation Network database for hepatic DCD
      allografts used in OLT. As of March 31, 2011, 85,148 patients received hepatic
      allografts from donation-after-brain-death (DBD) donors, and 2351 patients
      received hepatic allografts from DCD donors. We performed survival analysis using
      log-rank and Kaplan-Meier tests. We performed univariate and multivariate
      analyses using the Cox proportional hazards model. All statistics were performed
      with SPSS 15.0. RESULTS: Patients receiving hepatic DCD allografts had
      significantly worse survival compared with patients receiving hepatic DBD
      allografts. Pediatric patients who received a hepatic DCD allograft had similar
      survival to those who received a hepatic DBD allograft. The optimal recipient
      related characteristics were age <50 y, International Normalized Ratio <2.0,
      albumin >3.5 gm/dL, and cold ischemia time <8 h; optimal donor-related
      characteristics included age <50 y and donor warm ischemia time <20 min.
      CONCLUSIONS: By identifying certain characteristics, the transplant clinician's
      decision-making process can be assisted so that similar survival outcomes after
      OLT can be achieved with the use of hepatic DCD allografts.

PMID- 22583595
TI  - Antioxidant activities of curcumin and ascorbyl dipalmitate nanoparticles and
      their activities after incorporation into cellulose-based packaging films.
AB  - Curcumin (Ccm) and ascorbyl dipalmitate (ADP) nanoparticles (NPs) with average
      sizes of ~50 and ~80 nm, respectively, were successfully produced by rapid
      expansion of subcritical solutions into liquid solvents (RESOLV). Pluronic F127
      was employed as a stabilizer for both Ccm- and ADP-NPs in an aqueous receiving
      solution. Antioxidant activities of the Ccm-NPs and ADP-NPs were subsequently
      investigated using four assays, including 2,2-diphenyl-1-picrylhydrazyl (DPPH)
      radical scavenging, ABTS radical cation decolorization, beta-carotene bleaching,
      and ferric reducing antioxidant power. Ccm-NPs and ADP-NPs showed higher
      antioxidant activities than those of Ccm and ADP. Ccm-NPs yielded higher
      antioxidant activities than those of Ccm in ethanol and water (Ccm-EtOH and Ccm
      H(2)O), respectively. ADP-NPs yielded lower antioxidant activities than that of
      ADP in ethanol (ADP-EtOH) but higher activities than that of ADP in water (ADP
      H(2)O). Moreover, incorporation of Ccm-NPs and ADP-NPs into cellulose-based films
      indicated that Ccm-NPs and ADP-NPs significantly enhanced the antioxidant
      activities of Ccm and ADP (p < 0.05). Our results show that the environmentally
      benign supercritical CO(2) technique should be generally applicable to NP
      fabrication of other important bioactive ingredients, especially in liquid form.
      In addition, we suggest that Ccm-NPs and ADP-NPs can be used to reduce the dosage
      of Ccm and ADP and improve their bioavailability, and thus merit further
      investigation for antioxidant packaging film and coating applications.

PMID- 22583596
TI  - Regulation of ROCK1 via Notch1 during breast cancer cell migration into dense
      matrices.
AB  - BACKGROUND: The behaviour of tumour cells depends on factors such as genetics and
      the tumour microenvironment. The latter plays a crucial role in normal mammary
      gland development and also in breast cancer initiation and progression. Breast
      cancer tissues tend to be highly desmoplastic and dense matrix as a pre-existing
      condition poses one of the highest risk factors for cancer development. However,
      matrix influence on tumour cell gene expression and behaviour such as cell
      migration is not fully elucidated. RESULTS: We generated high-density (HD)
      matrices that mimicked tumour collagen content of 20 mg/cm3 that were ~14-fold
      stiffer than low-density (LD) matrix of 1 mg/cm3. Live-cell imaging showed breast
      cancer cells utilizing cytoplasmic streaming and cell body contractility for
      migration within HD matrix. Cell migration was blocked in the presence of both
      the ROCK inhibitor, Y-27632, and the MMP inhibitor, GM6001, but not by the drugs
      individually. This suggests roles for ROCK1 and MMP in cell migration are
      complicated by compensatory mechanisms. ROCK1 expression and protein activity,
      were significantly upregulated in HD matrix but these were blocked by treatment
      with a histone deacetylase (HDAC) inhibitor, MS-275. In HD matrix, the inhibition
      of ROCK1 by MS-275 was indirect and relied upon protein synthesis and Notch1.
      Inhibition of Notch1 using pooled siRNA or DAPT abrogated the inhibition of ROCK1
      by MS-275. CONCLUSION: Increased matrix density elevates ROCK1 activity, which
      aids in cell migration via cell contractility. The upregulation of ROCK1 is
      epigenetically regulated in an indirect manner involving the repression of
      Notch1. This is demonstrated from inhibition of HDACs by MS-275, which caused an
      upregulation of Notch1 levels leading to blockade of ROCK1 expression.

PMID- 22583597
TI  - Granulocytic sarcoma of the urinary bladder in a pediatric patient.
AB  - Granulocytic sarcoma (GS) is a rare tumor consisting of immature cells of
      granulocytic lineage. It is also called chloroma, referring to the green color of
      the tumor caused by high levels of myeloperoxidase in the cells. GS is often
      associated with acute myeloblastic leukemia. We report the case of a 4-year-old
      boy with a diagnosis of acute myeloblastic leukemia. Abdominal ultrasonography
      demonstrated a solid, vascularized, heterogeneous, polypoid formation involving
      the posterior wall of the bladder. Further studies confirmed the etiology of the
      tumor. On control ultrasonography, a marked decrease in tumor size 15 days after
      treatment was revealed. We describe the imaging findings in this patient and
      review the literature about this infrequent entity. Although imaging findings are
      not specific and considering that extramedullary involvement in leukemia is very
      sensitive to treatment, inclusion of GS in the differential diagnosis and
      awareness of the possible sites of occurrence and imaging features is essential
      to avoid unnecessary therapeutic measures.

PMID- 22583598
TI  - Gender difference in carotid intima-media thickness in type 2 diabetic patients:
      a 4-year follow-up study.
AB  - BACKGROUND: Different population studies have reported gender difference in
      carotid intima-media thickness (CIMT), which is proved to be a risk factor of
      cardiovascular diseases. However, few longitudinal researches examine this gender
      difference in type 2 diabetes mellitus (T2DM) patients. Therefore, we
      prospectively analyzed CIMT in T2DM patients over a 4-year follow-up period.
      METHODS: 355 T2DM patients (mean age 59 years; 54.9% women) were included in the
      present study. CIMT were measured using Color Doppler ultrasound. CIMT was
      measured at baseline (CIMT) in 2006 and at follow-up in 2010. Biochemical and
      clinical measurements were collected at baseline. RESULTS: Mean value of CIMT1
      and CIMT2 were 0.740 +/- 0.148 mm and 0.842 +/- 0.179 mm, respectively. Men had
      higher CIMT than women both at baseline and at follow-up (CIMT1: 0.762 +/- 0.149
      vs 0.723 +/- 0.146 mm, P = 0.0149; CIMT2: 0.880 +/- 0.189 vs 0.810 +/- 0.164 mm,
      P = 0.0002). Mean annual progression of CIMT (dCIMT) was 0.025 +/- 0.022 mm/year.
      dCIMT was larger in men than in women (0.030 +/- 0.025 vs 0.022 +/- 0.019 mm, P =
      0.0006). In multiple regression analyses, age was an independent risk factor of
      CIMT in both genders, while dCIMT was associated with age only in men.
      CONCLUSIONS: Gender difference in CIMT was confirmed in T2DM patients. Moreover,
      impact of ageing on CIMT progression only existed in men, which might be the
      reason that gender difference in CIMT increased with age.

PMID- 22583599
TI  - The places to be for neurogastroenterologists.

PMID- 22583601
TI  - Development of an enzyme-linked immunoassay for the quantitation of influenza
      haemagglutinin: an alternative method to single radial immunodiffusion.
AB  - BACKGROUND: The current method used to measure haemagglutinin (HA) content for
      influenza vaccine formulation, single radial immunodiffusion (SRID), is lengthy
      and relies on the availability of matched standardised homologous reagents. The
      2009 influenza pandemic highlighted the need to develop alternate assays that are
      able to rapidly quantitate HA antigen for vaccine formulation. OBJECTIVES: The
      aim of this work was to develop an enzyme-linked immunoassay (EIA) for the rapid
      quantitation of H1, H3, H5 and B influenza HA antigens. METHODS: Monoclonal
      antibodies (mAbs) selected for haemagglutination inhibition (HAI) activity were
      conjugated with horseradish peroxidase and used to establish a capture-detection
      EIA for the quantitation of HA antigen. Results were compared with the
      appropriate reference SRID assays to investigate assay performance and utility.
      RESULTS: Quantitation of HA antigen by EIA correlated well with current reference
      SRID assays. EIA results showed equivalent precision and exhibited a similar
      capacity to detect HA antigen in virus samples that had been used in either
      stability or splitting studies, or subjected to physical or chemical stresses.
      EIA exhibited greater sensitivity than SRID and has the potential to be used in
      high-throughput applications. CONCLUSIONS: We demonstrated the utility of EIA as
      a suitable alternative to SRID for HA antigen quantitation and stability
      assessment. This approach would lead to earlier availability of both seasonal and
      pandemic vaccines, because of the extended cross-reactivity of reagents.

PMID- 22583600
TI  - Intestinal barrier function in health and gastrointestinal disease.
AB  - Defects in intestinal barrier function are associated with diseases of the
      gastrointestinal (GI) tract. There is growing evidence that increases in
      intestinal permeability plays a pathogenic role in diseases, such as inflammatory
      bowel disease (IBD) and celiac disease, and functional bowel disorders, such as
      irritable bowel syndrome (IBS). This review takes a unique translational approach
      to discuss the physiological and pathophysiological mechanisms involved in the
      regulation of intestinal barrier function in IBS. The review summarizes the
      components of the intestinal barrier including the tight junction complex within
      the epithelium, and the methods used to assess gut permeability both in vitro and
      in vivo. Throughout the review, the authors have attempted to critically review
      the latest research from both experimental animal models and human studies to
      appraise whether intestinal barrier dysfunction is a primary cause of functional
      GI disorders, such as IBS....

PMID- 22583602
TI  - Normal tissue anatomy for oropharyngeal cancer: contouring variability and its
      impact on optimization.
AB  - PURPOSE: To evaluate the variability of organ at risk (OAR) delineation and the
      resulting impact on intensity modulated radiation therapy (IMRT) treatment plan
      optimization in head-and-neck cancer. METHODS AND MATERIALS: An expert panel of 3
      radiation oncologists jointly delineated OARs, including the parotid and
      submandibular glands (SM), pharyngeal constrictors (PC), larynx, and glottis
      (GL), in 10 patients with advanced oropharynx cancer in 3 contouring sessions,
      spaced at least 1 week apart. Contour variability and uncertainty, as well as
      their dosimetric impact on IMRT planning for each case, were assessed. RESULTS:
      The mean difference in total volume for each OAR was 1 cm(3) (sigma 0.5 cm(3)).
      Mean fractional overlap was 0.7 (sigma 0.1) and was highest (0.8) for the larynx
      and bilateral SMs and parotids and lowest (0.5) for PC. There were considerable
      spatial differences in contours, with the ipsilateral parotid and PC displaying
      the most variability (0.9 cm), which was most prominent in cases in which tumors
      obliterated fat planes. Both SMs and GL had the smallest differences (0.5 cm).
      The mean difference in OAR dose was 0.9 Gy (range 0.6-1.1 Gy, sigma 0.1 Gy), with
      the smallest difference for GL and largest for both SMs and the larynx.
      CONCLUSIONS: Despite substantial difference in OAR contours, optimization was
      barely affected, with a 0.9-Gy mean difference between optimizations, suggesting
      relative insensitivity of dose distributions for IMRT of oropharynx cancer to the
      extent of OARs.

PMID- 22583603
TI  - Monitoring of circulating tumor cells and their expression of EGFR/phospho-EGFR
      during combined radiotherapy regimens in locally advanced squamous cell carcinoma
      of the head and neck.
AB  - PURPOSE: The numbers of circulating tumor cells (CTCs) and their
      expression/activation of epidermal growth factor receptor (EGFR) during the
      course of combined chemo- or bioradiotherapy regimens as potential biomarkers of
      treatment efficacy in squamous cell carcinoma of the head and neck (SCCHN) were
      determined. METHODS AND MATERIALS: Peripheral blood samples from SCCHN patients
      with locally advanced stage IVA/B disease who were treated with concurrent
      radiochemotherapy or induction chemotherapy followed by bioradiation with
      cetuximab were included in this study. Using flow cytometry, the absolute number
      of CTCs per defined blood volume as well as their expression of EGFR and its
      phosphorylated form (pEGFR) during the course of treatment were assessed.
      RESULTS: Before treatment, we detected >=1 CTC per 3.75 mL blood in 9 of 31
      patients (29%). Basal expression of EGFR was detected in 100% and pEGFR in 55% of
      the CTC+ cases. The frequency of CTC detection was not influenced by induction
      chemotherapy. However, the number of CTC+ samples significantly increased after
      radiotherapy. This radiation-induced increase in CTC numbers was less pronounced
      when radiotherapy was combined with cetuximab compared to its combination with
      cisplatin/5-fluorouracil. The former treatment regimen was also more effective in
      reducing pEGFR expression in CTCs. CONCLUSIONS: Definitive radiotherapy regimens
      of locally advanced SCCHN can increase the number of CTCs and might thus
      contribute to a systemic spread of tumor cells. Further studies are needed to
      evaluate the predictive value of the radiation-induced increase in CTC numbers
      and the persistent activation of the EGFR signalling pathway in individual CTC+
      cases.

PMID- 22583604
TI  - A system for continual quality improvement of normal tissue delineation for
      radiation therapy treatment planning.
AB  - PURPOSE: To implement the "plan-do-check-act" (PDCA) cycle for the continual
      quality improvement of normal tissue contours used for radiation therapy
      treatment planning. METHODS AND MATERIALS: The CT scans of patients treated for
      tumors of the brain, head and neck, thorax, pancreas and prostate were selected
      for this study. For each scan, a radiation oncologist and a diagnostic
      radiologist, outlined the normal tissues ("gold" contours) using Radiation
      Therapy Oncology Group (RTOG) guidelines. A total of 30 organs were delineated.
      Independently, 5 board-certified dosimetrists and 1 trainee then outlined the
      same organs. Metrics used to compare the agreement between the dosimetrists'
      contours and the gold contours included the Dice Similarity Coefficient (DSC),
      and a penalty function using distance to agreement. Based on these scores,
      dosimetrists were re-trained on those organs in which they did not receive a
      passing score, and they were subsequently re-tested. RESULTS: Passing scores were
      achieved on 19 of 30 organs evaluated. These scores were correlated to organ
      volume. For organ volumes <8 cc, the average DSC was 0.61 vs organ volumes >=8
      cc, for which the average DSC was 0.91 (P=.005). Normal tissues that had the
      lowest scores included the lenses, optic nerves, chiasm, cochlea, and esophagus.
      Of the 11 organs that were considered for re-testing, 10 showed improvement in
      the average score, and statistically significant improvement was noted in more
      than half of these organs after education and re-assessment. CONCLUSIONS: The
      results of this study indicate the feasibility of applying the PDCA cycle to
      assess competence in the delineation of individual organs, and to identify areas
      for improvement. With testing, guidance, and re-evaluation, contouring
      consistency can be obtained across multiple dosimetrists. Our expectation is that
      continual quality improvement using the PDCA approach will ensure more accurate
      treatments and dose assessment in radiotherapy treatment planning and delivery.

PMID- 22583605
TI  - Insufficiency fractures after pelvic radiation therapy for uterine cervical
      cancer: an analysis of subjects in a prospective multi-institutional trial, and
      cooperative study of the Japan Radiation Oncology Group (JAROG) and Japanese
      Radiation Oncology Study Group (JROSG).
AB  - PURPOSE: To investigate pelvic insufficiency fractures (IF) after definitive
      pelvic radiation therapy for early-stage uterine cervical cancer, by analyzing
      subjects of a prospective, multi-institutional study. MATERIALS AND METHODS:
      Between September 2004 and July 2007, 59 eligible patients were analyzed. The
      median age was 73 years (range, 37-84 years). The International Federation of
      Gynecologic Oncology and Obstetrics stages were Ib1 in 35, IIa in 12, and IIb in
      12 patients. Patients were treated with the constant method, which consisted of
      whole-pelvic external-beam radiation therapy of 50 Gy/25 fractions and high-dose
      rate intracavitary brachytherapy of 24 Gy/4 fractions without chemotherapy. After
      radiation therapy the patients were evaluated by both pelvic CT and pelvic MRI at
      3, 6, 12, 18, and 24 months. Diagnosis of IF was made when the patients had both
      CT and MRI findings, neither recurrent tumor lesions nor traumatic histories. The
      CT findings of IF were defined as fracture lines or sclerotic linear changes in
      the bones, and MRI findings of IF were defined as signal intensity changes in the
      bones, both on T1- and T2-weighted images. RESULTS: The median follow-up was 24
      months. The 2-year pelvic IF cumulative occurrence rate was 36.9% (21 patients).
      Using Common Terminology Criteria for Adverse Events version 3.0, grade 1, 2, and
      3 IF were seen in 12 (21%), 6 (10%), and 3 patients (5%), respectively. Sixteen
      patients had multiple fractures, so IF were identified at 44 sites. The pelvic IF
      were frequently seen at the sacroileal joints (32 sites, 72%). Nine patients
      complained of pain. All patients' pains were palliated by rest or non-narcotic
      analgesic drugs. Higher age (>70 years) and low body weight (<50 kg) were thought
      to be risk factors for pelvic IF (P=.007 and P=.013, Cox hazard test).
      CONCLUSIONS: Cervical cancer patients with higher age and low body weight may be
      at some risk for the development of pelvic IF after pelvic radiation therapy.

PMID- 22583606
TI  - Normal tissue complication probability modeling of radiation-induced
      hypothyroidism after head-and-neck radiation therapy.
AB  - PURPOSE: To determine the dose-response relationship of the thyroid for radiation
      induced hypothyroidism in head-and-neck radiation therapy, according to 6 normal
      tissue complication probability models, and to find the best-fit parameters of
      the models. METHODS AND MATERIALS: Sixty-five patients treated with primary or
      postoperative radiation therapy for various cancers in the head-and-neck region
      were prospectively evaluated. Patient serum samples (tri-iodothyronine,
      thyroxine, thyroid-stimulating hormone [TSH], free tri-iodothyronine, and free
      thyroxine) were measured before and at regular time intervals until 1 year after
      the completion of radiation therapy. Dose-volume histograms (DVHs) of the
      patients' thyroid gland were derived from their computed tomography (CT)-based
      treatment planning data. Hypothyroidism was defined as increased TSH (subclinical
      hypothyroidism) or increased TSH in combination with decreased free thyroxine and
      thyroxine (clinical hypothyroidism). Thyroid DVHs were converted to 2 Gy/fraction
      equivalent doses using the linear-quadratic formula with alpha/beta = 3 Gy. The
      evaluated models included the following: Lyman with the DVH reduced to the
      equivalent uniform dose (EUD), known as LEUD; Logit-EUD; mean dose; relative
      seriality; individual critical volume; and population critical volume models. The
      parameters of the models were obtained by fitting the patients' data using a
      maximum likelihood analysis method. The goodness of fit of the models was
      determined by the 2-sample Kolmogorov-Smirnov test. Ranking of the models was
      made according to Akaike's information criterion. RESULTS: Twenty-nine patients
      (44.6%) experienced hypothyroidism. None of the models was rejected according to
      the evaluation of the goodness of fit. The mean dose model was ranked as the best
      model on the basis of its Akaike's information criterion value. The D(50)
      estimated from the models was approximately 44 Gy. CONCLUSIONS: The implemented
      normal tissue complication probability models showed a parallel architecture for
      the thyroid. The mean dose model can be used as the best model to describe the
      dose-response relationship for hypothyroidism complication.

PMID- 22583607
TI  - Regional normal lung tissue density changes in patients treated with stereotactic
      body radiation therapy for lung tumors.
AB  - PURPOSE: To describe regional lung tissue density changes in normal lung tissue
      of patients with primary and metastatic lung tumors who received stereotactic
      body radiation therapy (SBRT). METHODS AND MATERIALS: A total of 179 post-SBRT
      follow-up computed tomography (CT) scans of 62 patients who received SBRT between
      2003 and 2009 were studied. Median prescription dose was 54 Gy (range, 30-60 Gy)
      in 3 to 5 fractions. SBRT-induced lung density changes on post-SBRT follow-up CT
      were evaluated at approximately 3, 6, 12, 18, 24, and 30 months after treatment.
      Dose-response curves (DRC) were generated for SBRT-induced lung damage by
      averaging CT number (HU) changes for regions of the lungs receiving the same dose
      at 5-Gy intervals. RESULTS: For all follow-up interval periods, CT numbers
      linearly increased with dose until 35 Gy and were constant thereafter. For 3, 18,
      24, and 30 months, the rate of relative electron density increase with dose was
      approximately 0.24% per Gy. At 6 months, the rate was also similar below 20 Gy
      but then rose to 0.6% per Gy above this threshold. After 6 months, DRCs were
      mostly time-independent. When split between patients treated with 3 fractions of
      12 to 20 Gy (median, 20 Gy; average tumor volume, 12+/-16 cm3) and with >3
      fractions of 6 to 12.5 Gy (median, 9 Gy; average tumor volume, 30+/-40 cm3), DRCs
      differed significantly. In both cases, CT changes at 3, 18, 24, and 30 months
      were identical to those of the population DRC; however, patients who received >3
      fractions showed 6-month CT changes that were more than twice those for the group
      that received 3 fractions. CONCLUSIONS: This analysis of SBRT-induced normal lung
      density changes indicates that lung normal tissue has more pronounced self
      limited acute effects than late effects. Differences in acute CT changes
      following treatments in 3 fractions were considerably less than for treatments in
      >3 fractions.

PMID- 22583608
TI  - [18F]fluoromisonidazole and a new PET system with semiconductor detectors and a
      depth of interaction system for intensity modulated radiation therapy for
      nasopharyngeal cancer.
AB  - PURPOSE: The impact of a new type of positron emission tomography (New PET) with
      semiconductor detectors using 18F-labeled fluoromisonidazole (FMISO)-guided
      intensity modulated radiation therapy (IMRT) was compared with a state-of-the-art
      PET/computed tomography (PET/CT) system in nasopharyngeal cancer (NPC) patients.
      METHODS AND MATERIALS: Twenty-four patients with non-NPC malignant tumors
      (control group) and 16 patients with NPC were subjected to FMISO-PET. The
      threshold of the tumor-to-muscle (T/M) ratio in each PET scan was calculated. The
      hypoxic volume within the gross tumor volume (GTVh) was determined using each PET
      (NewPETGTVh and PET/CTGTVh, respectively). Dose escalation IMRT plans prescribing
      84 Gy to each GTVh were carried out. RESULTS: The threshold of the T/M ratio was
      1.35 for New PET and 1.23 for PET/CT. The mean volume of NewPETGTVh was
      significantly smaller than that of PET/CTGTVh (1.5+/-1.6 cc vs 4.7+/-4.6 cc,
      respectively; P=.0020). The dose escalation IMRT plans using New PET were
      superior in dose distribution to those using PET/CT. Dose escalation was possible
      in all 10 New PET-guided plans but not in 1 PET/CT-guided plan, because the
      threshold dose to the brainstem was exceeded. CONCLUSIONS: New PET was found to
      be useful for accurate dose escalation in FMISO-guided IMRT for patients with
      NPC.

PMID- 22583610
TI  - The evolving epidemic of drug-resistant tuberculosis among children in Cape Town,
      South Africa.
AB  - SETTING: Tygerberg Children's Hospital, Cape Town, South Africa. OBJECTIVE: To
      determine the prevalence and trend of drug resistance and human immunodeficiency
      virus (HIV) co-infection among children with culture-confirmed tuberculosis (TB).
      METHOD: Prospective surveillance from  March 2007 to February 2009, compared to
      three previous surveys (1994-1998, 2003-2005, 2005-2007). Drug susceptibility
      testing (DST) against isoniazid (INH) and rifampicin (RMP) was performed using
      genotypic and phenotypic testing. If multidrug-resistant TB (MDR-TB) was
      detected,  further DST against ethambutol (EMB) and second-line drugs was
      performed. RESULTS: A total of 294 children with a median age of 26 months (range
      3 days-13 years) were diagnosed with culture-confirmed TB. DST results were
      available for 292 (99.3%); 41 (14%) were INH-resistant, including  26 (8.9%) with
      MDR-TB. Four children (1.4%) had RMP monoresistance. EMB resistance was present
      in 12/24 (50%) MDR-TB cases tested. Two isolates were resistant to ofloxacin;
      none had extensively drug-resistant TB. Of those tested, 29% (63/217) were HIV
      infected. Any resistance to RMP increased  between 1994 and 2009 (P < 0.001), as
      did RMP monoresistance (P = 0.009) and MDR-TB (P < 0.001). Sensitivity was 87.5%
      and specificity 100% for genotypic compared to phenotypic testing for INH
      resistance. CONCLUSIONS: RMP, and consequently multidrug, resistance  is
      increasing among children with TB in this setting. EMB resistance is common among
      children with resistance to RMP and INH.

PMID- 22583609
TI  - Hemoglobin A1c improvements and better diabetes-specific quality of life among
      participants completing diabetes self-management programs: a nested cohort study.
AB  - BACKGROUND: Numerous primary care innovations emphasize patient-centered
      processes of care. Within the context of these innovations, greater understanding
      is needed of the relationship between improvements in clinical endpoints and
      patient-centered outcomes. To address this gap, we evaluated the association
      between glycosylated hemoglobin (HbA1c) and diabetes-specific quality of life
      among patients completing diabetes self-management programs. METHODS: We
      conducted a retrospective cohort study nested within a randomized comparative
      effectiveness trial of diabetes self-management interventions in 75 diabetic
      patients. Multiple linear regression models were developed to examine the
      relationship between change in HbA1c from baseline to one-year follow-up and
      Diabetes-39 (a diabetes-specific quality of life measure) at one year. RESULTS:
      HbA1c levels improved for the overall cohort from baseline to one-year follow-up
      (t (74) = 3.09, p = .0029). One-year follow up HbA1c was correlated with worse
      overall quality of life (r = 0.33, p = 0.004). Improvements in HbA1c from
      baseline to one-year follow-up were associated with greater D-39 diabetes control
      (beta = 0.23, p = .04) and D-39 sexual functioning (beta = 0.25, p = .03) quality
      of life subscales. CONCLUSIONS: Improvements in HbA1c among participants
      completing a diabetes self-management program were associated with better
      diabetes-specific quality of life. Innovations in primary care that engage
      patients in self-management and improve clinical biomarkers, such as HbA1c, may
      also be associated with better quality of life, a key outcome from the patient
      perspective.

PMID- 22583611
TI  - A complex microdeletion 17q12 phenotype in a patient with recurrent de novo
      membranous nephropathy.
AB  - BACKGROUND: Microdeletions on chromosome 17q12 cause of diverse spectrum of
      disorders and have only recently been identified as a rare cause of Mayer
      Rokitansky-Kuester-Hauser-Syndrome (MRKH), which is characterized by uterus
      aplasia +/- partial/complete vaginal aplasia in females with a regular karyotype.
      For the first time we report about a patient with a 17q12 microdeletion who is
      affected by MRKH in combination with a vascular and soft tissue disorder.
      Repeatedly she suffered from kidney transplant failure caused by consuming
      membranous nephropathy. CASE PRESENTATION: A 38-year-old female patient had been
      diagnosed with right kidney aplasia, left kidney dysplasia and significantly
      impaired renal function during infancy. Aged 16 she had to start hemodialysis.
      Three years later she received her first kidney transplant. Only then she was
      diagnosed with MRKH. The kidney transplant was lost due to consuming nephrotic
      syndrome caused by de novo membranous nephropathy, as was a second kidney
      transplant years later. In addition, a hyperelasticity syndrome affects the
      patient with congenital joint laxity, kyphoscoliosis, bilateral hip dysplasia,
      persistent hypermobility of both elbows, knees and hips. Her clinical picture
      resembles a combination of traits of a hypermobile and a vascular form of Ehlers
      Danlos-Syndrome, but no mutations in the COL3A1 gene was underlying. Instead,
      array-based comparative genomic hybridisation (CGH) detected a heterozygous 1.43
      Mb deletion on chromosome 17q12 encompassing the two renal developmental genes
      HNF1beta and LHX1. CONCLUSIONS: Deletions of HNF1beta have recently drawn
      significant attention in pediatric nephrology as an important cause of prenatally
      hyperechogenic kidneys, renal aplasia and renal hypodysplasia. In contrast,
      membranous nephropathy represents an often-unaccounted cause of nephrotic
      syndrome in the adult population. A causative connection between theses two
      conditions has never been postulated, but is suggestive enough in this case to
      hypothesize it.

PMID- 22583613
TI  - Global patterns in overweight among children and mothers in less developed
      countries.
AB  - OBJECTIVE: Past research has identified increases in national income and
      urbanization as key drivers of the global obesity epidemic. That work further
      identified educational attainment and urban residence as important moderators of
      the effects of national income. However, such work has tended to assume that
      children and adults respond in the same way to these factors. In the present
      paper, we evaluate how the socio-economic and country-level factors associated
      with obesity differ between children and their mothers. DESIGN: We modelled the
      associations between maternal education, country-level income and urban residence
      with mother's and children's weight status. SETTING: We analysed ninety-five
      nationally representative health and nutrition surveys conducted between 1990 and
      2008 from thirty-three less developed countries. SUBJECTS: Our sample included
      children aged 2-4 years (n 253 442) and their mothers (n 228 655). RESULTS:
      Consistent with prior research, we found that mothers' risk of overweight was
      positively associated with economic development, urban residence and maternal
      education. Additionally, economic development was associated with steeper
      increases in mothers' risk of overweight among those with low (v. high) levels of
      education and among those living in rural (v. urban) areas. However, these
      associations were different for children. Child overweight was not associated
      with maternal education and urban residence, and negatively associated with
      national income. CONCLUSIONS: We speculate that the distinctive patterns for
      children may arise from conditions in low- and middle-income developing countries
      that increase the risk of child underweight and poor nutrition.

PMID- 22583615
TI  - Induction of cell cycle arrest by GL331 via triggering an ATM-dependent DNA
      damage response in HepG2 cells.
AB  - GL331, a topoisomerase II inhibitor, has been found to trigger DNA damage
      response (DDR) to induce cell cycle arrest. However, the underlying mechanism has
      not yet been fully understood. This study investigated the molecular mechanism
      involved in the GL331-induced cell cycle arrest via DDR in human hepatocellular
      carcinoma HepG2 cells. As a result, GL331 could induce S arrest and up-regulate
      the phosphorylation of the histone H2AX variant (gamma-H2AX). Ataxia
      telangiectasia mutated protein kinase (ATM) was activated by GL331 through its
      autophosphorylation at Ser1981, which led to the activation of DNA damage
      signaling pathways including p53/p21 and Chk2/Cdc25A cascades. The DNA damage
      cascades triggered by GL331 finally induced the inactivation of cyclin A/Cdk2
      complexes to some extent. These phenomena could be reversed by ATM siRNA,
      followed by a partial disruption of S arrest. The present results suggested that
      the S arrest induced by GL331 via DDR was in an ATM-dependent manner to some
      degree.

PMID- 22583614
TI  - Leucine-sensitive hyperinsulinaemic hypoglycaemia in patients with loss of
      function mutations in 3-Hydroxyacyl-CoA Dehydrogenase.
AB  - BACKGROUND: Loss of function mutations in 3-Hydroxyacyl-CoA Dehydrogenase (HADH)
      cause protein sensitive hyperinsulinaemic hypoglycaemia (HH). HADH encodes short
      chain 3-hydroxacyl-CoA dehydrogenase, an enzyme that catalyses the penultimate
      reaction in mitochondrial beta-oxidation of fatty acids. Mutations in GLUD1
      encoding glutamate dehydrogenase, also cause protein sensitive HH (due to leucine
      sensitivity). Reports suggest a protein-protein interaction between HADH and GDH.
      This study was undertaken in order to understand the mechanism of protein
      sensitivity in patients with HADH mutations. METHODS: An oral leucine tolerance
      test was conducted in controls and nine patients with HADH mutations. Basal GDH
      activity and the effect of GTP were determined in lymphoblast homogenates from 4
      patients and 3 controls. Immunoprecipitation was conducted in patient and control
      lymphoblasts to investigate protein interactions. RESULTS: Patients demonstrated
      severe HH (glucose range 1.7-3.2 mmol/l; insulin range 4.8-63.8 mU/l) in response
      to the oral leucine load, this HH was not observed in control patients subjected
      to the same leucine load. Basal GDH activity and half maximal inhibitory
      concentration of GTP was similar in patients and controls. HADH protein could be
      co-immunoprecipitated with GDH protein in control samples but not in patient
      samples. CONCLUSIONS: We conclude that GDH and HADH have a direct protein-protein
      interaction, which is lost in patients with HADH mutations causing leucine
      induced HH. This is not associated with loss of inhibitory effect of GTP on GDH
      (as in patients with GLUD1 mutations).

PMID- 22583616
TI  - Identification of benzoxazole analogs as novel, S1P(3) sparing S1P(1) agonists.
AB  - A novel series of benzoxazole-derived S1P(1) agonists were designed based on
      scaffold hopping molecular design strategy combined with computational
      approaches. Extensive SAR studies led to the discovery of compound 17d as a
      selective S1P(1) agonist (over S1P(3)) with high CNS penetration and favorable
      DMPK properties. 17d also demonstrated in vivo pharmacological efficacy to reduce
      blood lymphocyte in mice after oral administration.

PMID- 22583617
TI  - E297G mutated bile salt export pump (BSEP) function enhancers derived from
      GW4064: structural development study and separation from farnesoid X receptor
      agonistic activity.
AB  - Bile salt export pump (BSEP) is a member of the ATP-binding cassette
      transmembrane transporter family and mediates biliary excretion of bile acids
      from hepatocytes. Several BSEP mutants, including Glu297Gly (E297G) and Asp482Gly
      (D482G), cause progressive familial intrahepatic cholestasis type 2. We
      previously found that compounds based on GW4064, a representative farnesoid X
      receptor (FXR) agonist, enhanced E297G BSEP transport activity. Here, we
      conducted a structure-activity relationship analysis of GW4064 derivatives aimed
      at separating E297G BSEP-function-promoting activity and FXR-agonistic activity.
      Among newly synthesized reversed-amide derivatives of previously reported GW4064
      analogs 2a-2f, we identified 7c as a selective BSEP function enhancer.

PMID- 22583619
TI  - Shewanella putrefaciens, a major microbial species related to tetrodotoxin (TTX)
      accumulation of puffer fish Lagocephalus lunaris.
AB  - AIMS: To investigate the major micro-organisms, which were isolated from internal
      organs, related to tetrodotoxin (TTX)-accumulation of puffer fish Lagocephalus
      lunaris. METHODS AND RESULTS: Puffer fish Lagocephalus lunaris around Chang
      Island in the Gulf of Thailand were collected to examine TTX-accumulation and
      microbial load in internal organs. The nine predominant micro-organisms isolated
      from the internal organs were determined TTX and studied in relation to the TTX
      accumulation of the puffer fish. Shewanella putrefaciens, a predominant bacterium
      and related to the TTX-accumulation of the puffer fish, was examined growth and
      TTX-production after culture in modified Zobell medium. The results revealed that
      the average TTX-accumulation of the puffer fish directly varied to the bacterium
      load periodically, year-round. Furthermore, it coincided with the growth and the
      TTX-production of the bacterium, which grew slowly but produced high TTX at low
      temperature. CONCLUSIONS: Shewanella putrefaciens was a major bacterium relating
      to TTX-accumulation of puffer fish L. lunaris. It resulted in high TTX
      accumulation of the puffer fish at low temperatures of seawater. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Temperature affected growth and TTX-production of S.
      putrefaciens that resulted in TTX accumulated in puffer fish L. lunaris.

PMID- 22583618
TI  - Kappa agonist CovX-Bodies.
AB  - Small peptidic kappa agonists were covalently linked to the reactive lysine of
      the CovX antibody to create compounds having potent activity at the kappa
      receptor with greatly extended half-life when compared to the parent peptide as
      exemplified by compound 20.

PMID- 22583620
TI  - Evaluation of obesity as an independent risk factor for medically attended
      laboratory-confirmed influenza.
AB  - BACKGROUND: The relationship between obesity and susceptibility to influenza
      infection in humans is unclear. Morbidly obese people were at an increased risk
      of complications from 2009 pandemic H1N1 influenza [A(H1N1)pdm09]. OBJECTIVE: The
      goal of this study was to determine whether medically attended, laboratory
      confirmed influenza is independently associated with obesity in adults with acute
      respiratory illness. PATIENTS/METHODS:   Adults >=20 years with a medical
      encounter for acute respiratory illness were recruited from a population cohort
      during the 2007-2008 (n = 903), 2008-2009 (n = 869), and 2009 pandemic (n = 851)
      season. Nasopharyngeal swabs were tested for influenza by real-time reverse
      transcription polymerase chain reaction. Body mass index (BMI) was calculated
      using data from the electronic medical record. Logistic regression evaluated the
      association between influenza and obesity, adjusting for gender, vaccination,
      age, and high-risk medical condition. RESULTS: Influenza was detected in 50% of
      patients in 2007-2008, 15% in 2008-2009, and 14% during the 2009 pandemic.
      Predominant seasonal viruses in this population were A/H3N2 in 2007-2008, and
      A/H1N1 and B in 2008-2009. Mean (+/-SD) BMI was 30.58 (+/-7.31) in patients with
      influenza and 30.93 (+/-7.55) in test-negative controls during all seasons. Mean
      BMI of patients with influenza did not vary by season. After adjusting for
      confounders, neither obesity nor extreme obesity were associated with influenza
      by season or for all years combined (OR 0.95: 95% CI 0.75, 1.20 and 1.10: 0.80,
      1.52, respectively, for obesity and extreme obesity, all years). CONCLUSIONS:
      Obesity was not associated with medically attended influenza among adults with
      acute respiratory illness in this population.

PMID- 22583621
TI  - Mouse strain specific gene expression differences for illumina microarray
      expression profiling in embryos.
AB  - BACKGROUND: In the field of mouse genetics the advent of technologies like
      microarray based expression profiling dramatically increased data availability
      and sensitivity, yet these advanced methods are often vulnerable to the
      unavoidable heterogeneity of in vivo material and might therefore reflect
      differentially expressed genes between mouse strains of no relevance to a
      targeted experiment. The aim of this study was not to elaborate on the usefulness
      of microarray analysis in general, but to expand our knowledge regarding this
      potential "background noise" for the widely used Illumina microarray platform
      surpassing existing data which focused primarily on the adult sensory and nervous
      system, by analyzing patterns of gene expression at different embryonic stages
      using wild type strains and modern transgenic models of often non-isogenic
      backgrounds. RESULTS: Wild type embryos of 11 mouse strains commonly used in
      transgenic and molecular genetic studies at three developmental time points were
      subjected to Illumina microarray expression profiling in a strain-by-strain
      comparison. Our data robustly reflects known gene expression patterns during mid
      gestation development. Decreasing diversity of the input tissue and/or increasing
      strain diversity raised the sensitivity of the array towards the genetic
      background. Consistent strain sensitivity of some probes was attributed to
      genetic polymorphisms or probe design related artifacts. CONCLUSION: Our study
      provides an extensive reference list of gene expression profiling background
      noise of value to anyone in the field of developmental biology and transgenic
      research performing microarray expression profiling with the widely used Illumina
      microarray platform. Probes identified as strain specific background noise
      further allow for microarray expression profiling on its own to be a valuable
      tool for establishing genealogies of mouse inbred strains.

PMID- 22583622
TI  - Home birth attendants in low income countries: who are they and what do they do?
AB  - BACKGROUND: Nearly half the world's babies are born at home. We sought to
      evaluate the training, knowledge, skills, and access to medical equipment and
      testing for home birth attendants across 7 international sites. METHODS: Face-to
      face interviews were done by trained interviewers to assess level of training,
      knowledge and practices regarding care during the antenatal, intrapartum and
      postpartum periods. The survey was administered to a sample of birth attendants
      conducting home or out-of-facility deliveries in 7 sites in 6 countries (India,
      Pakistan, Guatemala, Democratic Republic of the Congo, Kenya and Zambia).
      RESULTS: A total of 1226 home birth attendants were surveyed. Less than half the
      birth attendants were literate. Eighty percent had one month or less of formal
      training. Most home birth attendants did not have basic equipment (e.g., blood
      pressure apparatus, stethoscope, infant bag and mask manual resuscitator).
      Reporting of births and maternal and neonatal deaths to government agencies was
      low. Indian auxilliary nurse midwives, who perform some home but mainly clinic
      births, were far better trained and differed in many characteristics from the
      birth attendants who only performed deliveries at home. CONCLUSIONS: Home birth
      attendants in low-income countries were often illiterate, could not read numbers
      and had little formal training. Most had few of the skills or access to tests,
      medications and equipment that are necessary to reduce maternal, fetal or
      neonatal mortality.

PMID- 22583624
TI  - Perceptual learning 2012.

PMID- 22583623
TI  - Decoctions of Bridelia micrantha and Croton macrostachyus may have anticonvulsant
      and sedative effects.
AB  - Bridelia micrantha and Croton macrostachyus are medicinal plants used empirically
      in traditional medicine to treat epilepsy. In vivo mice model (maximal
      electroshock, strychnine, pentylenetetrazol, picrotoxin, isonicotinic hydrazide
      acid)-induced convulsions were used to evaluate the anticonvulsant activities of
      those plants. Diazepam-induced sleep was used for the evaluation of the sedative
      properties. B. micrantha protected 100, 80, 80, and 80% of mice against PIC, STR,
      PTZ and MES-induced seizures, respectively. C. macrostachyus at the doses 34 and
      67 mg/kg protected 80, 80, 80 and 60% of mice from PIC, STR, PTZ and MES-induced
      seizures, respectively. B. micrantha and C. macrostachyus also delayed the onset
      to seizures in INH test. B. micrantha was more potent than C. macrostachyus in
      protecting mice against convulsions. The co-administration of the sub effective
      dose of the decoction of B. micrantha or C. macrostachyus with the sub effective
      dose of diazepam or clonazepam resulted in a synergistic effect. The decoctions
      of B. micrantha and C. macrostachyus also exerted sedative activity by increasing
      the total duration of sleep induced by diazepam and by reducing the latency time
      to sleep. The effect of the decoctions of B. micrantha and C. macrostachyus
      suggests the presence of anticonvulsant activities that might show efficacy
      against secondarily generalized tonic-clonic seizures and primary generalized
      seizures in humans.

PMID- 22583626
TI  - Self-confidence, gender and academic achievement of undergraduate nursing
      students.
AB  - The aim of this study was to determine the self-confidence levels of nursing
      students and the factors related to such self-confidence. Data were obtained via
      a questionnaire for socio-demographic characteristics and a 'Self-Confidence
      Scale' prepared by the researchers. High self-confidence levels were noted in
      78.6% of female students and 92.3% of male students. While 84.5% of second-year
      students had high self-confidence levels, this rate was 76% in fourth-year
      students. Female nursing students were significantly less self-confident than
      male students. Self-confidence should be nurtured in a caring nursing curriculum;
      however, there is a lack of clarity as to what confidence means, how it is
      perceived by students and what educators can do to instil self-confidence in
      nursing students.

PMID- 22583625
TI  - Expression of lignocellulolytic enzymes in Pichia pastoris.
AB  - BACKGROUND: Sustainable utilization of plant biomass as renewable source for
      fuels and chemical building blocks requires a complex mixture of diverse enzymes,
      including hydrolases which comprise the largest class of lignocellulolytic
      enzymes. These enzymes need to be available in large amounts at a low price to
      allow sustainable and economic biotechnological processes.Over the past years
      Pichia pastoris has become an attractive host for the cost-efficient production
      and engineering of heterologous (eukaryotic) proteins due to several advantages.
      RESULTS: In this paper codon optimized genes and synthetic alcohol oxidase 1
      promoter variants were used to generate Pichia pastoris strains which
      individually expressed cellobiohydrolase 1, cellobiohydrolase 2 and beta
      mannanase from Trichoderma reesei and xylanase A from Thermomyces lanuginosus.
      For three of these enzymes we could develop strains capable of secreting gram
      quantities of enzyme per liter in fed-batch cultivations. Additionally, we
      compared our achieved yields of secreted enzymes and the corresponding activities
      to literature data. CONCLUSION: In our experiments we could clearly show the
      importance of gene optimization and strain characterization for successfully
      improving secretion levels. We also present a basic guideline how to correctly
      interpret the interplay of promoter strength and gene dosage for a successful
      improvement of the secretory production of lignocellulolytic enzymes in Pichia
      pastoris.

PMID- 22583627
TI  - Infrapatellar fat pad-derived mesenchymal stem cell therapy for knee
      osteoarthritis.
AB  - PURPOSE: The aim of the study was to determine if isolated mesenchymal stem cells
      (MSCs) derived from the infrapatellar fat pad could effectively improve clinical
      results when percutaneously injected into arthritic knees. LEVEL OF EVIDENCE:
      Therapeutic case-control study; Level III. METHODS: Twenty five stem cell
      injections combined with arthroscopic debridement were administered to patients
      with knee OA. A mean of 1.89 * 10(6) stem cells were prepared with approximately
      3.0 mL of platelet-rich plasma (PRP) and injected in the selected knees of
      patients in the study group. RESULTS: The mean Lysholm, Tegner activity scale,
      and VAS scores of patients in the study group improved significantly by the last
      follow-up visit. No major adverse events related to the injections were observed
      during the treatment and follow-up periods. The results were compared between the
      study and control groups, in which the patients had undergone arthroscopic
      debridement and PRP injection without stem cells. Although the preoperative mean
      Lysholm, Tegner activity scale, and VAS scores of the study group were
      significantly poorer than those of the control group, the clinical results at the
      last follow-up visit were similar and not significantly different between the two
      groups. CONCLUSIONS: The short-term results of our study are encouraging and
      demonstrate that infrapatellar fat pad-derived MSC therapy with intraarticular
      injections is safe, and provides assistance in reducing pain and improving
      function in patients with knee OA.

PMID- 22583628
TI  - Making informed policy decisions about newborn hearing screening.

PMID- 22583629
TI  - And how are the children?

PMID- 22583630
TI  - Obese and hungry in the suburbs: the hidden faces of food insecurity.

PMID- 22583631
TI  - The cost-effectiveness of universal newborn screening for bilateral permanent
      congenital hearing impairment: systematic review.
AB  - OBJECTIVE: Universal newborn hearing screening for bilateral permanent congenital
      hearing impairment is standard practice in many developed economies, but until
      there is clear evidence of cost-effectiveness, it remains a controversial use of
      limited health care resources. We conducted a formal systematic review of studies
      of newborn hearing screening that considered both costs and outcomes to produce a
      summary of the available evidence and to determine whether there was a need for
      further research. METHODS: A search was conducted of medical and nursing
      databases and gray literature websites by the use of multiple keywords. The
      titles and abstracts of studies were examined for preliminary inclusion if
      reference was made to newborn hearing screening, and to both costs and outcomes.
      Studies of potential relevance were independently assessed by 2 health economists
      for final inclusion in the review. Studies that met inclusion criteria were
      appraised by the use of existing guidelines for observational studies, economic
      evaluations and decision analytic models, and reported in a narrative literature
      review. RESULTS: There were 22 distinct observational or modeled evaluations of
      which only 2 clearly compared universal newborn hearing screening to risk factor
      screening for bilateral permanent congenital hearing impairment. Of these, the
      single evaluation that examined long-term costs and outcomes found that universal
      newborn hearing screening could be cost-saving if early intervention led to a
      substantial reduction in future treatment costs and productivity losses.
      CONCLUSIONS: There are only a small number of economic evaluations that have
      examined the long-term cost-effectiveness of universal newborn hearing screening.
      This is partly attributable to ongoing uncertainty about the benefits gained from
      the early detection and treatment of bilateral permanent congenital hearing
      impairment. There is a clear need for further research on long-term costs and
      outcomes to establish the cost-effectiveness of universal newborn hearing
      screening in relation to other approaches to screening, and to establish whether
      it is a good long term investment.

PMID- 22583632
TI  - Inter-agency collaboration in the care of children with complex chronic
      conditions.
AB  - OBJECTIVES: The purpose of this article was to describe the network of
      collaboration among agencies that serve children with complex chronic conditions
      (CCCs) and identify gaps in the network. METHODS: We surveyed representatives
      from agencies that serve children with CCCs in Forsyth County, North Carolina,
      about their agencies' existing and desired collaborations with other agencies in
      the network. We used Social Network Analytical (SNA) methods to describe gaps in
      the network. Mean out-degree and in-degree centrality (number of collaborative
      ties extending from or directed toward an agency) and density (ratio of extant
      ties to all possible ties) were measured. RESULTS: In this network with 3658
      possible collaborative ties, care-coordination agencies and pediatric practices
      reported the highest existing collaborations with other agencies (out-degree
      centrality: 32 and 30, respectively). Pediatric practices reported strong ties
      with subspecialty clinics (density: 73%), but weak ties with family support
      services (density: 3%). Pediatric practices and subspecialty clinics (in-degree:
      26) received the highest collaborative ties from other agencies. Support services
      and durable medical equipment (DME) companies reported low ties with other
      agencies (out-degree: 7 and 10, respectively). Nursing agencies reported the
      highest desired collaborations (out-degree: 18). Support services, pediatric
      practices, and care-coordination programs had the highest in-degree centrality
      (7, 6, and 6, respectively) for desired collaborations. Nursing agencies and
      support services had the greatest gaps in collaboration. CONCLUSION: Although
      collaboration exists among agencies serving children with CCCs, there are many
      gaps in the network. Future studies should explore barriers and facilitators to
      inter-agency collaborations and whether increased collaboration in the network
      improves patient-level outcomes.

PMID- 22583633
TI  - Molecular evolution of pentatricopeptide repeat genes reveals truncation in
      species lacking an editing target and structural domains under distinct selective
      pressures.
AB  - BACKGROUND: Pentatricopeptide repeat (PPR) proteins are required for numerous RNA
      processing events in plant organelles including C-to-U editing, splicing,
      stabilization, and cleavage. Fifteen PPR proteins are known to be required for
      RNA editing at 21 sites in Arabidopsis chloroplasts, and belong to the PLS class
      of PPR proteins. In this study, we investigate the co-evolution of four PPR genes
      (CRR4, CRR21, CLB19, and OTP82) and their six editing targets in Brassicaceae
      species. PPR genes are composed of approximately 10 to 20 tandem repeats and each
      repeat has two alpha-helical regions, helix A and helix B, that are separated by
      short coil regions. Each repeat and structural feature was examined to determine
      the selective pressures on these regions. RESULTS: All of the PPR genes examined
      are under strong negative selection. Multiple independent losses of editing site
      targets are observed for both CRR21 and OTP82. In several species lacking the
      known editing target for CRR21, PPR genes are truncated near the 17th PPR repeat.
      The coding sequences of the truncated CRR21 genes are maintained under strong
      negative selection; however, the 3' UTR sequences beyond the truncation site have
      substantially diverged. Phylogenetic analyses of four PPR genes show that
      sequences corresponding to helix A are high compared to helix B sequences.
      Differential evolutionary selection of helix A versus helix B is observed in both
      plant and mammalian PPR genes. CONCLUSION: PPR genes and their cognate editing
      sites are mutually constrained in evolution. Editing sites are frequently lost by
      replacement of an edited C with a genomic T. After the loss of an editing site,
      the PPR genes are observed with three outcomes: first, few changes are detected
      in some cases; second, the PPR gene is present as a pseudogene; and third, the
      PPR gene is present but truncated in the C-terminal region. The retention of
      truncated forms of CRR21 that are maintained under strong negative selection even
      in the absence of an editing site target suggests that unrecognized function(s)
      might exist for this PPR protein. PPR gene sequences that encode helix A are
      under strong selection, and could be involved in RNA substrate recognition.

PMID- 22583634
TI  - Editorial comment.

PMID- 22583635
TI  - Long-term decrease in bladder cancer recurrence with hexaminolevulinate enabled
      fluorescence cystoscopy.
AB  - PURPOSE: We assessed the impact of hexaminolevulinate fluorescence cystoscopic
      detection of papillary, nonmuscle invasive bladder cancer on the long-term
      recurrence rate. MATERIALS AND METHODS: Long-term followup was assessed in 551
      participants enrolled in a prospective, randomized study of fluorescence
      cystoscopy for Ta or T1 urothelial bladder cancer. In the original study 280
      patients in the white light cystoscopy group and 271 in the fluorescence
      cystoscopy group were followed with cystoscopy for 3, 6 and 9 months after
      initial resection or until recurrence. A study extension protocol was done for
      long-term followup of these patients. RESULTS: Followup information was obtained
      for 261 of the 280 patients (93%) in the white light group and 255 of the 271
      (94%) in the fluorescence group. Median followup in the white light and
      fluorescence groups was 53.0 and 55.1 months, and 83 (31.8%) and 97 patients
      (38%) remained tumor free, respectively. Median time to recurrence was 9.4 months
      in the white light group and 16.4 months in the fluorescence group (p = 0.04).
      The intravesical therapy rate was similar in the 2 groups (46% and 45%,
      respectively). Cystectomy was done in 22 of 280 cases (7.9%) in the white light
      group and in 13 of the 271 (4.8%) in the fluorescence group (p = 0.16).
      CONCLUSIONS: Hexaminolevulinate fluorescence cystoscopy significantly improves
      long-term bladder cancer time to recurrence with a trend toward improved bladder
      preservation.

PMID- 22583637
TI  - Gender specific differences in bladder cancer.

PMID- 22583636
TI  - Detection of previously unidentified metastatic disease as a leading cause of
      screening failure in a phase III trial of zibotentan versus placebo in patients
      with nonmetastatic, castration resistant prostate cancer.
AB  - PURPOSE: Understanding the extent of disease in asymptomatic patients with
      castration resistant prostate cancer is important when making treatment decisions
      and designing clinical trials. The ENTHUSE M0 (ENdoTHelin A USE) trial
      (NCT00626548) was a large phase III study comparing the endothelin A receptor
      antagonist zibotentan with placebo in patients with nonmetastatic, castration
      resistant prostate cancer. The study was stopped prematurely after early efficacy
      review indicated that it was unlikely to meet its co-primary objectives of
      improved overall and progression-free survival vs placebo. Screening failed in an
      unexpectedly high number of patients. We investigated this screening failure rate
      to promote better classification of patients thought to have nonmetastatic
      castration resistant prostate cancer and inform the design of future clinical
      trials in this setting. MATERIALS AND METHODS: The number of patients enrolled in
      and subsequently excluded from study was analyzed by geographic region and by the
      specialty of the investigating clinician (oncology or urology) who enrolled the
      study patients. RESULTS: Of 2,577 patients enrolled in a total of 350 hospital
      based centers in 39 countries screening failed in 1,155 (45%). The most common
      reason for screening failure was the detection of metastatic disease in 32% of
      all screened patients and in 71% of those in whom screening failed. The leading
      reasons for failed screening did not differ between investigator specialties
      overall or by geographic region. CONCLUSIONS: The high frequency of asymptomatic
      metastasis in men thought to have nonmetastatic, castration resistant prostate
      cancer highlights the importance of periodic staging assessments for the
      condition. Optimal treatment modalities may differ for metastatic and
      nonmetastatic disease.

PMID- 22583638
TI  - A new vision for clinical research.

PMID- 22583639
TI  - Injection therapy for reflux: why it works and why it fails.

PMID- 22583640
TI  - Small renal mass with contralateral large renal mass: remove large renal mass
      first in staged fashion. Pro.

PMID- 22583641
TI  - How has genitourinary trauma management changed?

PMID- 22583642
TI  - Imaging calculi in pregnancy--is the future ultra low dose computerized
      tomography with iterative reconstruction technique?

PMID- 22583643
TI  - Editorial comment.

PMID- 22583644
TI  - Small renal mass with contralateral large renal mass: remove large renal mass
      first in staged fashion. Con.

PMID- 22583645
TI  - Community perceptions of infectious diseases, antibiotic use and antibiotic
      resistance in context of environmental changes: a study in Odisha, India.
AB  - BACKGROUND: The public health impact of environmental changes and the faceless
      threat of antibiotic resistance are currently among the top global health
      challenges. Community understanding of health, diseases and medicines in relation
      to the changing environment is necessary to mitigate the impact of these changes
      on health and for prudent use of antibiotics. OBJECTIVE: The objective is to
      explore community perceptions of infectious diseases, antibiotic use and
      antibiotic resistance in the context of environmental changes. METHODS: A
      qualitative study was conducted among community members with various backgrounds
      in education, gender, age and occupation of two districts of Odisha, India. Eight
      focus groups discussions and ten individual interviews were conducted. Data were
      analysed using content analysis. RESULTS: Two themes emerged: 'Interpretation of
      infectious diseases and health hazards in the context of environmental changes',
      and 'Understanding of antibiotic use and its consequences for resistance
      development and the environment'. The participants perceived that nowadays there
      is irregularity in the occurrence of seasons, particularly an increase in average
      temperature, which is influencing health. Participants' perceptions of infectious
      diseases, antibiotic use and resistance varied according to their social
      environment. Furthermore, they perceived that improved sanitation, choice of
      alternative medicine and awareness and education on prudent use of antibiotics
      are probably some ways to prevent antibiotic resistance. CONCLUSIONS: The
      participants perceived that climate variability is increasing and that this has
      health consequences for the community. They also hypothesized an
      interrelationship between the environment, infectious diseases and medicine use,
      particularly antibiotics. This is helpful for further empirical studies.

PMID- 22583647
TI  - Berry morphology and composition in irrigated and non-irrigated grapevine (Vitis
      vinifera L.).
AB  - The present study was carried out in a 5-year-old vineyard (Vitis vinifera L.,
      cv. Aglianico) located in Southern Italy. Half of the plants (IRR) were fully
      irrigated, whereas the other half were not irrigated (NIRR). In both of the
      treatments, plant water status, gas exchange, photosynthetic efficiency and
      productive performance were determined. The arid conditions resulted in
      significant decreases in stem water potential in NIRR (minimum values of -1.34
      and -1.52 MPa in IRR and NIRR, respectively). The values of yield per plant,
      cluster weight and total berry weight were significantly higher in IRR. Grape
      berries were separated into four weight classes, and morphometric and microscopic
      analyses were carried out to measure and calculate berry skin characteristics.
      Irrigation determined a marked shift toward heavier (+23% in the class >= 1.25 g)
      and bigger (336.35 mm3 vs 299.15 mm3) berries, and induced significant changes in
      other morphometric berry parameters. No differences among berry weight classes
      and irrigation treatments were observed for berry skin thickness. In all of the
      berry weight classes, total anthocyanins extracted from berry skins were
      significantly higher in NIRR than in IRR (12301.53 and 9585.52 mg kg-1 fresh
      berry skin, respectively), and appeared to be positively related to berry weight,
      whereas total flavonols were not significantly different between the two
      treatments. Qualitative changes in the levels of single anthocyanin and flavonol
      compounds were detected between IRR and NIRR. In addition, iron, copper and zinc,
      whose high concentration can negatively affect wine quality, were significantly
      higher in the IRR treatment. The results highlighted that the absence of
      irrigation did not determine decreases in grape quality. Such data can be of
      primary importance in environments where water availability is by far the most
      important limiting factor for plant growth.

PMID- 22583646
TI  - Quantitative connection between polyglutamine aggregation kinetics and
      neurodegenerative process in patients with Huntington's disease.
AB  - BACKGROUND: Despite enormous progress in elucidating the biophysics of
      aggregation, no cause-and-effect relationship between protein aggregation and
      neurodegenerative disease has been unequivocally established. Here, we derived
      several risk-based stochastic kinetic models that assess genotype/phenotype
      correlations in patients with Huntington's disease (HD) caused by the expansion
      of a CAG repeat. Fascinating disease-specific aspects of HD include the
      polyglutamine (polyQ)-length dependence of both age at symptoms onset and the
      propensity of the expanded polyQ protein to aggregate. In vitro, aggregation of
      polyQ peptides follows a simple nucleated growth polymerization pathway. Our
      models that reflect polyQ aggregation kinetics in a nucleated growth
      polymerization divided aggregate process into the length-dependent nucleation and
      the nucleation-dependent elongation. In contrast to the repeat-length dependent
      variability of age at onset, recent studies have shown that the extent of
      expansion has only a subtle effect on the rate of disease progression, suggesting
      possible differences in the mechanisms underlying the neurodegenerative process.
      RESULTS: Using polyQ-length as an index, these procedures enabled us for the
      first time to establish a quantitative connection between aggregation kinetics
      and disease process, including onset and the rate of progression. Although the
      complexity of disease process in HD, the time course of striatal
      neurodegeneration can be precisely predicted by the mathematical model in which
      neurodegeneration occurs by different mechanisms for the initiation and
      progression of disease processes. Nucleation is sufficient to initiate neuronal
      loss as a series of random events in time. The stochastic appearance of
      nucleation in a cell population acts as the constant risk of neuronal cell damage
      over time, while elongation reduces the risk by nucleation in proportion to the
      increased extent of the aggregates during disease progression. CONCLUSIONS: Our
      findings suggest that nucleation is a critical step in gaining toxic effects to
      the cell, and provide a new insight into the relationship between polyQ
      aggregation and neurodegenerative process in HD.

PMID- 22583648
TI  - Essential oil of the leaves of Eugenia uniflora L.: antioxidant and antimicrobial
      properties.
AB  - Essential oil (EO) of the leaves of Eugenia uniflora L. (Brazilian cherry tree)
      was evaluated for its antioxidant, antibacterial and antifungal properties. The
      acute toxicity of the EO administered by oral route was also evaluated in mice.
      The EO exhibited antioxidant activity in the DPPH, ABTS and FRAP assays and
      reduced lipid peroxidation in the kidney of mice. The EO also showed
      antimicrobial activity against two important pathogenic bacteria, Staphylococcus
      aureus and Listeria monocytogenes, and against two fungi of the Candida species,
      C. lipolytica and C. guilliermondii. Acute administration of the EO by the oral
      route did not cause lethality or toxicological effects in mice. These findings
      suggest that the EO of the leaves of E. uniflora may have the potential for use
      in the pharmaceutical industry.

PMID- 22583649
TI  - Medium optimization and potential hepatoprotective effect of mycelial
      polysaccharides from Pholiota dinghuensis Bi against carbon tetrachloride-induced
      acute liver injury in mice.
AB  - Response surface methodology was employed to optimize the medium compositions for
      the production of mycelial polysaccharide from Pholiota dinghuensis Bi (PDP). As
      a result, the optimal medium for crude PDP production was determined as follows
      (g/L): glucose 36.0, corn flour 11.8, peptone 3.0, yeast extract 5.4, KH(2)PO(4)
      1.0, and MgSO(4) 1.5. In a verification experiment, a yield of 756 +/- 38 mg/L
      crude PDP was obtained. Furthermore, biochemical assay and histopathological
      analysis showed that crude PDP exerted significant hepatoprotective effect in a
      dose-dependent manner against carbon tetrachloride (CCl(4))-induced acute liver
      injury. Crude PDP prevented the increase of activities of serum alanine
      aminotransferase and aspartate aminotransferase, reduced the formation of
      malondialdehyde and enhanced the activities of superoxide dismutase and
      glutathione peroxidase in CCl(4)-induced hepatotoxicity in mice.

PMID- 22583650
TI  - Suppression of adhesion molecule expression by phenanthrene-containing extract of
      bulbils of Chinese Yam in vascular smooth muscle cells through inhibition of
      MAPK, Akt and NF-kappaB.
AB  - Atherosclerosis is a chronic inflammatory disease associated with increased
      expression of adhesion molecules in vascular smooth muscle cells (VSMCs). The
      objective of this study was to examine the in vitro effects of extract from
      aerial Bulbil of Dioscorea batatas Decne (Db-Ex) on the ability to suppress the
      expression of adhesion molecules induced by TNF-alpha. We also identified
      bioactive components from a methanol extract. VSMCs pre-exposed to Db-Ex (10-100
      MUg/ml) were stimulated with TNF-alpha (10 ng/ml). Preincubation of VSMCs for 2 h
      with Db-Ex dose-dependently inhibited TNF-alpha-induced adhesion of THP-1
      monocytic cells and mRNA and protein expression of vascular cell adhesion
      molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). Db-Ex
      treatment decreased ROS production and the amount of phosphorylated form of p38,
      ERK, JNK and Akt in TNF-alpha-stimulated cells, suggesting that Db-Ex inhibits
      adhesion molecule expression possibly through MAPK and Akt regulation. Db-Ex also
      suppressed TNF-alpha-activation NK-kappaB. This effect was mediated through
      degradation of IkappaBalpha and nuclear translocation of the p65 subunit of NF
      kappaB. These results suggest that Db-Ex inhibits monocyte adhesion and the TNF
      alpha-mediated induction of adhesion molecules in VSMC by downregulating the
      MAPK/Akt/NF-kappaB signaling pathway, which may explain the ability of Db-Ex to
      suppress inflammation within the atherosclerotic lesion.

PMID- 22583651
TI  - Arachidonate-enriched triglyceride oil does not promote tumor development in a
      rat medium-term multi-organ carcinogenesis model.
AB  - The modifying potential on tumor development of arachidonate-enriched
      triglyceride oil (ARA-oil) containing approximately 40% arachidonic acid was
      investigated in a medium-term multi-organ carcinogenesis bioassay using male and
      female F344 rats. The animals were sequentially given five carcinogens with
      different target sites in the first 4 weeks, and then administered ARA-oil for 24
      weeks at dietary levels of 0% (control), 1.25%, 2.5% or 5.0%. No statistically
      significant differences in incidences and multiplicities of hyperplastic and
      neoplastic lesions were showed in the large intestine in either sex. In the
      liver, kidney, and lung in both sexes, and the mammary gland and uterus in
      females, tumor promoting potential was not evident with ARA-oil treatment. ARA
      oil did not affect the quantitative data for glutathione S-transferase placental
      form positive foci of the liver. Increased induction of hyperplastic or
      neoplastic lesions in the urinary bladder and thyroid in ARA-oil-treated groups
      was without dose dependence. In addition, a second experiment with ARA-oil only
      administration for 8-week revealed no effects on cellular proliferation in the
      urinary bladder or thyroid in either sex. These results indicate that ARA-oil has
      no tumor promoting potential in any organs or tissues initiated with the five
      carcinogens applied in the present study.

PMID- 22583652
TI  - Embryonic developmental toxicity of selenite in zebrafish (Danio rerio) and
      prevention with folic acid.
AB  - Selenium (Se) is an essential micronutrient, but also a potential toxin, which
      may be absorbed in excess. Relatively little is known about selenium
      embryotoxicity in zebrafish. In this study, we evaluated the effect of selenite
      exposure in zebrafish embryos. Selenite treatment decreased survival and resulted
      in abnormal development in a dose- and time-dependent manner. We observed
      irregular growth of neurons in selenite treated embryos, characterized by the
      absence of neurons in the brain, trunk and tail. Selenite exposure also induced
      defects in heart function, such as bradycardia and cardiac dysplasia with
      irregular and smaller chamber shape. In addition, selenite exposure caused
      ectopic cell proliferation, apoptosis, and a change in the pattern of DNA
      methylation. Our results suggested that supplementation with folic acid (FA)
      ameliorated the cardiac and neural defects in selenite-treated embryos. In
      conclusion, we demonstrated that selenite exposure caused cardiac and neural
      defects in zebrafish embryos and that folic acid protected against this
      embryotoxicity. It will give insight into the risk assessment and prevention of
      Se-mediated embryotoxicity.

PMID- 22583653
TI  - Dairy food intake of Australian children and adolescents 2-16 years of age: 2007
      Australian National Children's Nutrition and Physical Activity Survey.
AB  - OBJECTIVE: Dairy food consumption is important for Australian children as it
      contributes key nutrients such as protein and Ca. The aim of the present paper is
      to describe dietary intake from dairy foods for Australian children aged 2-16
      years in 2007. DESIGN: Secondary analysis of a quota-sampled survey using
      population-weighted, 1 d (24 h) dietary recall data. SETTING: Australian national
      survey conducted from February to August 2007. SUBJECTS: Children (n 4487) aged 2
      16 years. RESULTS: Most Australian children consumed dairy foods (84-98 %), with
      the proportion consuming tending to decrease with age and males consuming
      significantly more than females from the age of 4 years. Milk was the most
      commonly consumed dairy food (58-88 %) and consumed in the greatest amount (243
      384 g/d). Most children consumed regular-fat dairy products. The contribution of
      dairy foods to total energy intake decreased with age; from 22 % of total energy
      at age 2-3 years to 11 % at age 14-16 years. This trend was similar for all
      nutrients analysed. Dairy food intake peaked between 06.00 and 10.00 hours
      (typical breakfast hours) corresponding with the peak in dairy Ca intake.
      Australian children (older than 4 years) did not reach recommendations for dairy
      food intake, consuming <=2 servings/d. CONCLUSIONS: The under-consumption of
      dairy foods by Australian children has important implications for intake of key
      nutrients and should be addressed by multiple strategies.

PMID- 22583654
TI  - The application of observational data in translational medicine: analyzing
      tobacco-use behaviors of adolescents.
AB  - BACKGROUND: Translational Medicine focuses on "bench to bedside", converting
      experimental results into clinical use. The "bedside to bench" transition remains
      challenging, requiring clinicians to define true clinical need for laboratory
      study. In this study, we show how observational data (an eleven-year data survey
      program on adolescent smoking behaviours), can identify knowledge gaps and
      research questions leading directly to clinical implementation and improved
      health care. We studied gender-specific trends (2000-2010) in Italian students to
      evaluate the specific impact of various anti-smoking programs, including
      evaluation of perceptions of access to cigarettes and health risk. METHODS: The
      study used, ESPAD-Italia(r) (European School Survey Project on Alcohol and other
      Drugs), is a nationally representative sample of high-school students. The
      permutation test for joinpoint regression was used to calculate the annual
      percent change in smoking. Changes in smoking habits by age, perceived
      availability and risk over a 11-year period were tested using a gender-specific
      logistic model and a multinomial model. RESULTS: Gender-stratified analysis
      showed 1) decrease of lifetime prevalence, then stabilization (both genders); 2)
      decrease in last month and occasional use (both genders); 3) reduction of
      moderate use (females); 4) no significant change in moderate use (males) and in
      heavy use (both genders). Perceived availability positively associates with
      prevalence, while perceived risk negatively associates, but interact with
      different effects depending on smoking patterns. In addition, government
      implementation of public policies concerning access to tobacco products in this
      age group during this period presented a unique background to examine their
      specific impact on behaviours. CONCLUSION: Large observational databases are a
      rich resource in support of translational research. From these observations, key
      clinically relevant issues can be identified and form the basis for further
      clinical studies. The ability to identify patterns of behaviour and gaps in
      available data translates into new experiments, but also impacts development of
      public policy and reveals patterns of clinical reality. The observed global
      decrease in use is countered by stabilization in number of heavy smokers.
      Increased cigarette cost has not reduced use. While perceived risk of smoking may
      prevent initial experimentation, how government policies impact the perception of
      risk is not easily quantifiable.

PMID- 22583655
TI  - Validity of assessing people experiencing mental illness who have offended using
      the Camberwell Assessment of Need-Forensic and Health of the Nation Outcome
      Scales-Secure.
AB  - Evidence-based practices for forensic mental health services have been slow to
      develop, and there is a lack of measures that assess the mental health and
      criminogenic needs of people experiencing mental illness who have offended. The
      present study aimed to investigate the interrelationship between a clinician
      rated forensic mental health needs assessment (Health of the Nation Outcomes
      Scales-Secure (HoNOS-S)), a forensic mental health needs assessment that
      considers both clinician and patient perspectives (Camberwell Assessment of Need
      Forensic (CANFOR)), and measures of general and violent recidivism (Level Service
      Case Management Inventory (LS-CMI) and HCR-20 Violence Risk Assessment Scheme
      (HCR-20)). Needs were assessed for 72 forensic patients aged between 20 and 62
      years of age, located in a secure forensic mental health facility. The findings
      revealed significant positive correlations between the HoNOS-S, CANFOR, and HCR
      20. Only the CANFOR was positively correlated with the LS-CMI, and uniquely
      contributed variance to the HCR-20. Patients and nurses differed in the total
      number of needs and met needs they identified as present. The findings suggest
      that the collaborative approach of the CANFOR might be more appropriate for
      measuring outcomes in the treatment of individuals experiencing mental illness
      who have offended.

PMID- 22583656
TI  - Protein tyrosine phosphatase (PTP) inhibition enhances chromosomal stability
      after genotoxic stress: decreased chromosomal instability (CIN) at the expense of
      enhanced genomic instability (GIN)?
AB  - Inappropriate survival signaling after DNA damage may facilitate clonal expansion
      of genetically compromised cells, and it is known that protein tyrosine
      phosphatase (PTP) inhibitors activate key survival pathways. In this study we
      employed the genotoxicant, hexavalent chromium [Cr(VI)], which is a well
      documented carcinogen of occupational and environmental concern. Cr(VI) induces a
      complex array of DNA damage, including DNA double strand breaks (DSBs). We
      recently reported that PTP inhibition bypassed cell cycle arrest and abrogated
      Cr(VI)-induced clonogenic lethality. Notably, PTP inhibition resulted in an
      increase in forward mutations at the HPRT locus, supporting the hypothesis that
      PTP inhibition in the presence of DNA damage may lead to genomic instability
      (GIN), via cell cycle checkpoint bypass. The aim of the present study was to
      determine the effect of PTP inhibition on DNA DSB formation and chromosomal
      integrity after Cr(VI) exposure. Diploid human lung fibroblasts were treated with
      Cr(VI) in the presence or absence of the PTP inhibitor, sodium orthovanadate, for
      up to 24h, and cells were analyzed for DNA DSBs and chromosomal damage. Cr(VI)
      treatment induced a rapid increase in DNA DSBs, and a significant increase in
      total chromosomal damage (chromatid breaks and gaps) after 24h. In sharp
      contrast, PTP inhibition abrogated both DNA DSBs and chromosomal damage after
      Cr(VI) treatment. In summary, PTP inhibition in the face of Cr(VI) genotoxic
      stress decreases chromosomal instability (CIN) but increases mutagenesis, which
      we postulate to be a result of error-prone DNA repair.

PMID- 22583658
TI  - New guidelines for treatment of traumatic dental injuries in the primary
      dentition.

PMID- 22583657
TI  - Prdx1 deficiency in mice promotes tissue specific loss of heterozygosity mediated
      by deficiency in DNA repair and increased oxidative stress.
AB  - The loss of the H(2)O(2) scavenger protein encoded by Prdx1 in mice leads to an
      elevation of reactive oxygen species (ROS) and tumorigenesis of different
      tissues. Loss of heterozygosity (LOH) mutations could initiate tumorigenesis
      through loss of tumor suppressor gene function in heterozygous somatic cells. A
      connection between the severity of ROS and the frequency of LOH mutations in vivo
      has not been established. Therefore, in this study, we characterized in vivo LOH
      in ear fibroblasts and splenic T cells of 3-4 month old Prdx1 deficient mice. We
      found that the loss of Prdx1 significantly elevates ROS amounts in T cells and
      fibroblasts. The basal amounts of ROS were higher in fibroblasts than in T cells,
      probably due to a less robust Prdx1 peroxidase activity in the former. Using Aprt
      as a LOH reporter, we observed an elevation in LOH mutation frequency in
      fibroblasts, but not in T cells, of Prdx1(-/-) mice compared to Prdx1(+/+) mice.
      The majority of the LOH mutations in both cell types were derived from mitotic
      recombination (MR) events. Interestingly, Mlh1, which is known to suppress MR
      between divergent sequences, was found to be significantly down-regulated in
      fibroblasts of Prdx1(-/-) mice. Therefore, the combination of elevated ROS
      amounts and down-regulation of Mlh1 may have contributed to the elevation of MR
      in fibroblasts of Prdx1(-/-) mice. We conclude that each tissue may have a
      distinct mechanism through which Prdx1 deficiency promotes tumorigenesis.

PMID- 22583659
TI  - International Association of Dental Traumatology guidelines for the management of
      traumatic dental injuries: 3. Injuries in the primary dentition.
AB  - Traumatic injuries to the primary dentition present special problems and the
      management is often different as compared with the permanent dentition. The
      International Association of Dental Traumatology (IADT) has developed a consensus
      statement after a review of the dental literature and group discussions.
      Experienced researchers and clinicians from various specialities were included in
      the task group. In cases where the data did not appear conclusive,
      recommendations were based on the consensus opinion or majority decision of the
      task group. Finally, the IADT board members were giving their opinion and
      approval. The primary goal of these guidelines is to delineate an approach for
      the immediate or urgent care for management of primary teeth injuries. The IADT
      cannot and does not guarantee favorable outcomes from strict adherence to the
      guidelines, but believe that their application can maximize the chances of a
      positive outcome.

PMID- 22583660
TI  - Area-based socio-economic disadvantage and tuberculosis incidence.
AB  - OBJECTIVE: To examine neighborhood-level influences on tuberculosis (TB)
      incidence in a multilevel population-based sample. DESIGN: All incident TB cases
      in Washington State, United States (n = 2161), reported between 1 January 2000
      and 31 December 2008 were identified. Multivariate Poisson analysis was used at
      the ZIP Code tabulation area (ZCTA) level, which allowed for further exploration
      of area-specific influences on TB incidence. RESULTS: A significant association
      was found between indices of socio-economic position (SEP) and TB incidence in
      Washington State, with a clear gradient of higher rates observed among lower ZCTA
      socio-economic quartiles. Compared to the wealthiest SEP quartile, the relative
      incidence of TB in successively lower quartiles was respectively 2.7, 4.1 and
      10.4 (P trend <0.001). In multivariate analyses, the addition of area-level race,
      ethnicity and country of birth significantly attenuated this association
      (adjusted incidence rate ratios 2.3, 2.6, 5.7; P trend <0.001). CONCLUSION: This
      study found a significant inverse association between area measures of socio
      economic status (SES) and TB incidence across ZCTAs in Washington State, even
      after adjusting for individual age and sex and area-based race, ethnicity and
      foreign birth. These results emphasize the importance of neighborhood context and
      the need to target prevention efforts to low-SES neighborhoods.

PMID- 22583661
TI  - Pandemic 2009 influenza A (H1N1) infection among 2009 Hajj Pilgrims from Southern
      Iran: a real-time RT-PCR-based study.
AB  - BACKGROUND: Hajj is a mass gathering undertaken annually in Mecca, Saudi Arabia.
      The 2009 Hajj coincided with both the pandemic influenza A/H1N1 2009
      (A(H1N1)pdm09) and seasonal types of influenza A viruses. The interaction between
      pandemic influenza and Hajj could cause both a high level of mortality among the
      pilgrims and the spread of infection in their respective countries upon their
      return home. OBJECTIVE: The present study attempted to determine the point
      prevalence of A(H1N1)pdm09 among returning Iranian pilgrims, most of whom had
      been vaccinated for seasonal influenza but not A(H1N1)pdm09. METHODS: Pharyngeal
      swabs were collected from 305 pilgrims arriving at the airport in Shiraz, Iran.
      RNA was extracted from the samples and A(H1N1)pdm09 and other seasonal influenza
      A viruses were detected using TaqMan real-time PCR. For A(H1N1)pdm09-positive
      samples, the sensitivity to oseltamivir was also evaluated. RESULTS: Subjects
      included 132 (43.3%) men and 173 (56.7%) women, ranging in age from 24 to 65
      years. The A(H1N1)pdm09 virus was detected in five (1.6%) pilgrims and other
      influenza A viruses in eight (2.6%). All the A(H1N1)pdm09 were sensitive to
      oseltamivir. CONCLUSIONS: Only five cases were found to be positive for
      A(H1N1)pdm09, and it seems unlikely that the arrival of infected pilgrims to
      their homelands would cause an outbreak of a new wave of infection there. Thus,
      the low morbidity and mortality rates among the pilgrims could be attributed to
      the characteristics of A(H1N1)pdm09, which causes morbidity and mortality in a
      way similar to the seasonal influenza infections, absence of high-risk
      individuals among the Iranian pilgrims, and the instructions given to them about
      contact and hand hygiene, and respiratory etiquette.

PMID- 22583662
TI  - Prevalence of consanguineous marriages in South Sinai, Egypt.
AB  - A total of 3961 married couples from six major geographical areas representing
      the South Sinai governorates in Egypt were studied to assess the rate of
      consanguineous marriage. The population of six selected areas (St Catherines,
      Nuweiba, Abu Rudeis, Ras Sudr, El Tor and Abu Zenima) were subdivided into
      Bedouin, urban and mixed populations. A questionnaire-based interview was
      conducted showing that the consanguinity rate in this region is 37.5%, with the
      highest rate recorded in Abu Rudeis (52.3%) and lowest rate in Nuweiba (24.1%).
      Consanguinity was significantly higher among the Bedouin population compared with
      the urban population in Abu Rudeis, Ras Sudr, El Tor and Abu Zenima, while in St
      Catherines and Nuweiba there was no statistically significant difference. Among
      consanguineous couples, 5%, 60% and 35% were double first cousins, first cousins
      and second cousins respectively. The mean inbreeding coefficient alpha of the
      studied population was 0.01845.

PMID- 22583663
TI  - PalliPA: How can general practices support caregivers of patients at their end of
      life in a home-care setting? A study protocol.
AB  - BACKGROUND: The care of patients with a life-threatening, progressive and far
      advanced illness in a home-care setting requires appropriate individual care and
      requires the active support of family caregivers. General practice teams are
      usually the primary care givers and first contact and are best placed to offer
      support to family caregivers and to recognise and respond to the burden of care
      giving on family members. The aim of this project is to develop a best practice
      model for engaging with and supporting family caregivers. FINDINGS: The project
      is framed as an exploratory trial for a subsequent implementation study, covering
      phases 0, I and II of the MRC (Medical Research Council) framework for
      development, design and evaluation of complex interventions. The project is a
      multi-method procedure and has two phases. In the first phase, which has already
      been completed, we used a reflective practice procedure where general practice
      teams were asked about how they currently deal with family caregivers. In the
      second phase, a participatory action research approach aims to improve
      identification and response to when support is necessary for family caregivers.
      Ten participating general practice teams each enrol 40 eligible patients and
      their family caregiver, to identify structures and tools feasible for use in
      their practice. Standardised self-reported questionnaires (Burden Scale for
      Family Caregivers and Quality of Life Questionnaire Core 15 Palliative) are being
      applied at study inclusion (prior to or during the implementation period) and
      after 6 and 12 months to explore implementation effects. Qualitative assessment
      of general practice teams' experiences will be triangulated with the quantitative
      evaluation of the implementation. DISCUSSION: This two-step approach, which is
      appropriate to primary palliative care in the German health care context, will
      enable general practice teams to develop feasible, acceptable and successful
      strategies for the implementation of best practice to successfully support family
      caregivers of patients at the end of life.

PMID- 22583665
TI  - Experimental infection of the honeybee (Apis mellifera L.) with the chronic bee
      paralysis virus (CBPV): infectivity of naked CBPV RNAs.
AB  - Chronic paralysis is an infectious and contagious disease of the honeybee (Apis
      mellifera L.) and is caused by the chronic bee paralysis virus (CBPV). This
      disease leads to death in adult bees and is therefore a serious threat for colony
      health. CBPV is a positive single-stranded RNA virus and its genome is composed
      of two RNA segments, RNA 1 and RNA 2, 3674 nt and 2305 nt, respectively. Although
      CBPV shares some characteristics with viruses classified into families
      Nodaviridae and Tombusviridae, it has not been assigned to any viral taxa yet.
      The characterisation of CBPV proteins and their functions are needed to better
      understand the mechanisms of CBPV infection. However, since honeybee cell lines
      are not yet available, experimental infection of adult bees is the only method
      currently available to propagate the virus. With the objective of studying CBPV
      proteins using the viral genome, we used experimental infection in adult bees to
      evaluate the infectivity of naked CBPV RNAs by direct inoculation. Our results
      demonstrated that an injection of naked RNAs, ranging from 10(9) to 10(10) CBPV
      copies, caused chronic paralysis. Bees inoculated with naked RNA showed chronic
      paralysis signs 5 days after inoculation. Moreover, injected RNAs replicated and
      generated viral particles. We therefore provide an in vivo experimental model
      that will be useful tool for further studies by using a reverse genetics system.

PMID- 22583664
TI  - Isolation of Plasmodium falciparum by flow-cytometry: implications for single
      trophozoite genotyping and parasite DNA purification for whole-genome high
      throughput sequencing of archival samples.
AB  - BACKGROUND: Flow cytometry and cell sorting are powerful tools enabling the
      selection of particular cell types within heterogeneous cell mixtures. These
      techniques, combined with whole genome amplification that non-specifically
      amplify small amounts of starting DNA, offer exciting new opportunities for the
      study of malaria genetics. Among them, two are tested in this paper: (1) single
      cell genotyping and (2) parasite DNA purification for subsequent whole genome
      sequencing using shotgun technologies. METHODS: The method described allows
      isolation of Plasmodium falciparum trophozoites, genotyping and whole genome
      sequencing from the blood of infected patients. For trophozoite isolation,
      parasite and host nuclei are stained using propidium iodide (PI) followed by flow
      cytometry and cell sorting to separate trophozoites from host cells. Before
      genotyping or sequencing, whole genome amplification is used to increase the
      amount of DNA within sorted samples. The method has been specifically designed to
      deal with frozen blood samples. RESULTS AND CONCLUSION: The results demonstrate
      that single trophozoite genotyping is possible and that cell sorting can be
      successfully applied to reduce the contaminating host DNA for subsequent whole
      genome sequencing of parasites extracted from infected blood samples.

PMID- 22583666
TI  - The cumulative impacts of reclamation and dredging on the marine ecology and land
      use in the Kingdom of Bahrain.
AB  - This article assesses the ecological and economic impacts of land reclamation and
      dredging through consulting recent environmental impact assessment reports.
      Geographic features of Bahrain during 1963-2008 are produced using Geographical
      Information System. Extensive but inexpensive shallow coastal areas and tidal
      flats have been reclaimed particularly from 1997 to 2007 at a high rate of 21
      km(2)/year. Formal records show the increase in the original land mass by the
      year 2008 to be 91 km(2). An estimated total cumulative loss of major habitats
      resulting from 10 reclamation projects was around 153.58 km(2). Also much larger
      scale impacts should be considered resulting from the borrow areas used for the
      extraction of sand or infill materials. A number of key habitats and species are
      affected in the vicinity of these projects. The study attempts to assign a
      monetary value to the marine ecosystem functions. There is a need for efficient
      coastal zone management to regulate a sustainable use of the marine resources.

PMID- 22583668
TI  - Muscle MRI in female carriers of dystrophinopathy.
AB  - BACKGROUND AND PURPOSE: Duchenne muscular dystrophy carriers represent a rare
      condition that needs to be recognized because of the possible implications for
      prenatal diagnosis. Muscle biopsy is currently the diagnostic instrument of
      choice in sporadic patients. We wanted to verify whether muscle magnetic
      resonance imaging (MRI) could identify a pattern of involvement suggestive of
      this condition and whether it was similar to that reported in Duchenne and Becker
      muscular dystrophy. METHODS: Evaluation of pelvic and lower limb MRI scans of 12
      dystrophinopathy carriers was performed. RESULTS: We found a frequent involvement
      of the quadratus femoris, gluteus maximus and medius, biceps femoris long head,
      adductor magnus, vasti and paraspinal muscles, whilst the popliteus, iliopsoas,
      recti abdominis, sartorius, and gracilis were relatively spared. Asymmetry was a
      major feature on MRI; it could be detected significantly more often than with
      sole clinical examination and even in patients without weakness. CONCLUSIONS: The
      pattern we describe here is similar to that reported in Duchenne and Becker
      muscular dystrophy, although asymmetry represents a major distinctive feature.
      Muscle MRI was more sensitive than clinical examination for detecting single
      muscle involvement and asymmetry. Further studies are needed to verify the
      consistency of this pattern in larger cohorts and to assess whether muscle MRI
      can improve diagnostic accuracy in carriers with normal dystrophin staining on
      muscle biopsy.

PMID- 22583667
TI  - DcR3 binds to ovarian cancer via heparan sulfate proteoglycans and modulates
      tumor cells response to platinum with corresponding alteration in the expression
      of BRCA1.
AB  - BACKGROUND: Overcoming platinum resistance is a major obstacle in the treatment
      of Epithelial Ovarian Cancer (EOC). In our previous work Decoy Receptor 3 (DcR3)
      was found to be related to platinum resistance. The major objective of this work
      was to define the cellular interaction of DcR3 with EOC and to explore its
      effects on platinum responsiveness. METHODS: We studied cell lines and primary
      cultures for the expression of and the cells ability to bind DcR3. Cells were
      cultured with DcR3 and then exposed to platinum. Cell viability was determined by
      MTT assay. Finally, the cells molecular response to DcR3 was studied using real
      time RT-PCR based differential expression arrays, standard RT-PCR, and Western
      blot. RESULTS: High DcR3 in the peritoneal cavity of women with EOC is associated
      with significantly shorter time to first recurrence after platinum based therapy
      (p = 0.02). None-malignant cells contribute DcR3 in the peritoneal cavity. The
      cell lines studied do not secrete DcR3; however they all bind exogenous DcR3 to
      their surface implying that they can be effected by DcR3 from other sources.
      DcR3s protein binding partners are minimally expressed or negative, however, all
      cells expressed the DcR3 binding Heparan Sulfate Proteoglycans (HSPGs) Syndecans
      2, and CD44v3. DcR3 binding was inhibited by heparin and heparinase. After DcR3
      exposure both SKOV-3 and OVCAR-3 became more resistant to platinum with 15% more
      cells surviving at high doses. On the contrary CaOV3 became more sensitive to
      platinum with 20-25% more cell death. PCR array analysis showed increase
      expression of BRCA1 mRNA in SKOV-3 and OVCAR-3 and decreased BRCA1 expression in
      CaOV-3 after exposure to DcR3. This was confirmed by gene specific real time PCR
      and Western blot analysis. CONCLUSIONS: Non-malignant cells contribute to the
      high levels of DcR3 in ovarian cancer. DcR3 binds readily to EOC cells via HSPGs
      and alter their responsiveness to platinum chemotherapy. The paradoxical
      responses seen were related to the expression pattern of HSPGs available on the
      cells surface to interact with. Although the mechanism behind this is not
      completely known alterations in DNA repair pathways including the expression of
      BRCA1 appear to be involved.

PMID- 22583669
TI  - Synthesis, biological evaluation and 3D-QSAR studies of novel 4,5-dihydro-1H
      pyrazole niacinamide derivatives as BRAF inhibitors.
AB  - A series of novel 4,5-dihydropyrazole derivatives containing niacinamide moiety
      as potential V600E mutant BRAF kinase (BRAF(V600E)) inhibitors were designed and
      synthesized. Results of the bioassays against BRAF(V600E) and WM266.4 human
      melanoma cell line showed several compounds to be endowed potent activities with
      IC(50) and GI(50) value in low micromolar range, among which compound 27e, (5-(4
      Chlorophenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)6-methylpyridin-3
      yl methanone (IC(50)=0.20 MUM, GI(50)=0.89 MUM) was bearing the best bioactivity
      comparable with the positive control Sorafenib. Docking simulation was performed
      to determine the probable binding model and 3D-QSAR model was built to provide
      more pharmacophore understanding that could use to design new agents with more
      potent BRAF(V600E) inhibitory activity.

PMID- 22583670
TI  - Radiolabeling of RGD peptide and preliminary biological evaluation in mice
      bearing U87MG tumors.
AB  - 2-[(18)F]Fluoroethyl azide ([(18)F]FEA) and terminal alkynyl modified propioloyl
      RGDfK were selected in this study. [(18)F]FEA was prepared by nucleophilic
      radiofluorination of 2-azidoethyl 4-toluenesulfonate with radiochemical yield of
      71 +/- 4% (n = 5, decay-corrected). We assessed the various conditions of the
      CuAAC reaction between [(18)F]FEA and propioloyl RGDfK, which included peptide
      concentration, reaction time, temperature and catalyst dosage. The (18)F-labeled
      RGD peptide ([(18)F]F-RGDfK) could be obtained in 60 min by a two-step
      radiochemical synthesis route, with total radiochemical yield of 60 +/- 2% (n =
      3, decay-corrected) through click chemistry. [(18)F]F-RGDfK showed high stability
      in phosphate buffered saline and new-born calf serum. Micro-PET imaging at 1 h
      post injection of [(18)F]F-RGDfK showed medium concentration of radioactivity in
      tumors while much decreased concentration in tumors in the blocking group. These
      results showed that [(18)F]F-RGDfK obtained by click chemistry maintained the
      affinity and specificity of the RGDfK peptide to integrin alpha(v)beta(3). This
      study provided useful information for peptide radiofluorination by using click
      chemistry.

PMID- 22583671
TI  - Genetic and environmental influences on individual differences in cortisol level
      and circadian rhythm in middle childhood.
AB  - Individuals differ widely in cortisol output over the day, but the etiology of
      these individual differences remains poorly understood. Twin studies are useful
      for quantifying genetic and environmental influences on the variation in cortisol
      output, lending insight into underlying influences on the components of
      Hypothalamic-Pituitary-Adrenal (HPA) axis functioning. Salivary cortisol was
      assayed on 446 twin pairs (157 monozygotic, 289 dizygotic; ages 7-8). Parents
      helped youth collect saliva 30 min after waking, mid-afternoon, and 30 min prior
      to bedtime across 3 consecutive days. We used hierarchical linear modeling to
      extract predicted cortisol levels and to distinguish cortisol's diurnal rhythm
      using a slopes-as-outcome piecewise growth curve model; two slopes captured the
      morning-to-afternoon and afternoon-to-evening rhythm, respectively. Separate
      genetic models were then fit to cortisol level at waking, mid-afternoon, and
      evening as well as the diurnal rhythm across morning-to-afternoon and afternoon
      to-evening hours. Three results from these analyses are striking. First, morning
      to-afternoon cortisol level showed the highest additive genetic variance
      (heritability), consistent with prior research. Second, cortisol's diurnal rhythm
      had an additive genetic component, particularly across the morning-to-afternoon
      hours. In contrast, additive genetic variation did not significantly contribute
      to variation in afternoon-to-evening slope. Third, the majority of variance in
      cortisol concentration was associated with shared family environments. In
      summary, both genetic and environmental factors influence cortisol's circadian
      rhythm, and they do so differentially across the day.

PMID- 22583672
TI  - Effects of short periods of warm water fluctuations on reproductive endocrine
      axis of the pejerrey (Odontesthes bonariensis) spawning.
AB  - The aim of this study was to assess fluctuations in daily water temperature in
      Chascomus Lagoon during one year, and to evaluate whether the highest temperature
      recorded during pejerrey spawning season can produce an endocrine disruption on
      brain-pituitary-gonads axis. Fish were subjected to daily temperature
      fluctuations: 17  degrees C to 19  degrees C (reproductive control), 19  degrees
      C to 25  degrees C, and 19  degrees C to 27  degrees C. After 8 days, ten fish
      per treatment were sacrificed and gene expression of gonadotropin-releasing
      hormone (GnRH-I, GnRH-II, GnRH-III), gonadotropin subunits-beta (FSH-beta, LH
      beta), glycoprotein hormone-alpha (GPH-alpha), gonadotropin receptors (FSH-R, LH
      R), and gonadal aromatase (cyp19a1a) was analyzed. Also, plasma levels of sexual
      steroids and gonadal reproductive status were studied. Fish exposed to high
      temperature fluctuations quit spawning, presenting clear signs of gonadal
      regression. Fish recovered its spawning activity 11 weeks after heat treatment.
      At endocrine level, GnRH-I and FSH-beta in both sexes, LH-beta and GPH-alpha in
      males and FSH-R, LH-R and cyp19a1a in females decreased significantly in treated
      fish. Also, a strong reduction in plasma sex steroid levels was found for both
      sexes. This study demonstrated that pulses of warm water in natural environment
      during pejerrey spawning season can disrupt all levels of the reproductive axis,
      impairing reproduction.

PMID- 22583673
TI  - Experiences of motherhood when suffering from mental illness: a hermeneutic
      study.
AB  - Being a mother is inseparable from women's existential life. Mothers with mental
      illness struggle with conflicting and distressing feelings related to motherhood.
      They seldom obtain the necessary support to increase their control over the
      determinants of their role as a mother, thus their opportunity of improving their
      own and their children's mental health is weakened. The aim of this study was to
      explore the experiences of being a mother with mental illness. The research
      question was: How can mothers' experiences of motherhood when suffering from
      mental illness be understood? The understanding emerged through a hermeneutical
      interpretation of the empirical material on four different levels of abstraction.
      The inductive-deductive approach, inspired by the philosophy of Gadamer, was
      used. The mothers' experiences were understood in their way of struggling to
      become good enough mothers, managing to become the mother they longed to be,
      being present in the caring relationship with their child, as well as being
      recognized as a mother and living openly and honestly in relationships with
      others. Addressing the existential needs of motherhood is important for their
      improvement and recovery, as well as for promoting their children's mental health
      and well-being.

PMID- 22583675
TI  - Stocking characteristics and perceived increases in sales among small food store
      managers/owners associated with the introduction of new food products approved by
      the Special Supplemental Nutrition Program for Women, Infants, and Children.
AB  - OBJECTIVE: The present study assessed the impact of the 2009 food packages
      mandated by the Special Supplemental Nutrition Program for Women, Infants, and
      Children (WIC) on perceived sales, product selection and stocking habits of
      small, WIC-authorized food stores. DESIGN: A cross-sectional study involving in
      depth interviews with store managers/owners. SETTING: Small, WIC-authorized food
      stores in eight major cities in the USA. SUBJECTS: Fifty-two store
      managers/owners who had at least 1 year of experience in the store prior to study
      participation. RESULTS: The WIC-approved food products (fresh, canned and frozen
      fruits; fresh, canned and frozen vegetables; wholegrain/whole-wheat bread; white
      corn/whole-wheat tortillas; brown rice; lower-fat milk (<2 %)) were acquired in
      multiple ways, although acquisition generally occurred 1-2 times/week. Factors
      such as customer requests (87 %), refrigerator/freezer availability (65 %) and
      profitability (71 %) were rated as very important when making stocking decisions.
      Most managers/owners perceived increases in sales of new WIC-approved foods
      including those considered most profitable (wholegrain/whole-wheat bread (89 %),
      lower-fat milk (89 %), white corn/whole wheat tortillas (54 %)), but perceived no
      changes in sales of processed fruits and vegetables. Supply mechanisms and
      frequency of supply acquisition were only moderately associated with perceived
      sales increases. CONCLUSIONS: Regardless of type or frequency of supply
      acquisition, perceived increases in sales provided some evidence for the
      potential sustainability of these WIC policy efforts and translation of this
      policy-based strategy to other health promotion efforts aimed at improving
      healthy food access in underserved communities.

PMID- 22583674
TI  - Degree of conversion of two-step etch-and-rinse adhesives: In situ micro-Raman
      analysis.
AB  - OBJECTIVES: DC of three commercial two-step etch-and-rinse adhesives across the
      dentine-adhesive interface was investigated using micro-Raman spectroscopy. The
      hypothesis tested was that no difference in DC would exist among the adhesives
      tested. METHODS: Adper Scotchbond 1XT (3M ESPE), Prime&Bond NT (Dentsply DeTrey),
      and Ambar (FGM) were applied on human dentine disks (n=9). Composite increments
      of 2mm were then applied on the adhesive surface. Raman spectra were collected
      along the dentine-adhesive interface. The relative intensities of the peaks
      associated with the mineral (PO(4)(3-) at 960cm(-1)) and the adhesive (CC at
      1640cm(-1); phenyl CC at 1610cm(-1)) were used to identify the adhesive within
      the hybrid layer and calculate its DC. RESULTS: Adper Scotchbond 1XT and Ambar
      showed similar DC (79+/-7% and 77+/-7%, respectively), while a lower DC was found
      for Prime&Bond NT (70+/-7%; p<0.05). CONCLUSIONS: The hypothesis tested was
      rejected because differences were found among the adhesives tested. The
      difference in DC among the three adhesive systems can be attributed to different
      monomer compositions and solvents. Further studies are needed to correlate DC
      with other mechanical properties of these adhesives. CLINICAL SIGNIFICANCE:
      Insufficient polymerization of an adhesive can result in a weak hybrid layer, and
      the presence of unreacted monomers may result in degradation of the polymeric
      network, decreasing the strength and longevity of the bond. In the present study,
      Adper Scotchbond 1XT and Ambar performed significantly better than Prime&Bond NT.

PMID- 22583676
TI  - Phylogeography and dispersal in the velvet gecko (Oedura lesueurii), and
      potential implications for conservation of an endangered snake (Hoplocephalus
      bungaroides).
AB  - BACKGROUND: To conserve critically endangered predators, we also need to conserve
      the prey species upon which they depend. Velvet geckos (Oedura lesueurii) are a
      primary prey for the endangered broad-headed snake (Hoplocephalus bungaroides),
      which is restricted to sandstone habitats in southeastern Australia. We sequenced
      the ND2 gene from 179 velvet geckos, to clarify the lizards' phylogeographic
      history and landscape genetics. We also analysed 260 records from a longterm (3
      year) capture-mark-recapture program at three sites, to evaluate dispersal rates
      of geckos as a function of locality, sex and body size. RESULTS: The genetic
      analyses revealed three ancient lineages in the north, south and centre of the
      species' current range. Estimates of gene flow suggest low dispersal rates,
      constrained by the availability of contiguous rocky habitat. Mark-recapture
      records confirm that these lizards are highly sedentary, with most animals moving
      < 30 m from their original capture site even over multi-year periods. CONCLUSION:
      The low vagility of these lizards suggests that they will be slow to colonise
      vacant habitat patches; and hence, efforts to restore degraded habitats for broad
      headed snakes may need to include translocation of lizards.

PMID- 22583677
TI  - The molecular basis of HIV entry.
AB  - Infection by HIV starts when the virus attaches to a susceptible cell. For viral
      replication to continue, the viral envelope must fuse with a cellular membrane,
      thereby delivering the viral core to the cytoplasm, where the RNA genome is
      reverse-transcribed. The key players in this entry by fusion are the envelope
      glycoprotein, on the viral side, and CD4 and a co-receptor, CCR5 or CXCR4, on the
      cellular side. Here, the interplay of these molecules is reviewed from cell
      biological, structural, mechanistic, and modelling-based perspectives. Hypotheses
      are evaluated regarding the cellular compartment for entry, the transfer of virus
      through direct cell-to-cell contact, the sequence of molecular events, and the
      number of molecules involved on each side of the virus-cell divide. An emerging
      theme is the heterogeneity among the entry mediators on both sides, a diversity
      that affects the efficacy of entry inhibitors, be they small-molecule ligands,
      peptides or neutralizing antibodies. These insights inform rational strategies
      for therapy as well as vaccination.

PMID- 22583678
TI  - A retrospective pooled analysis of response patterns and risk factors in
      recurrent malignant glioma patients receiving a nitrosourea-based chemotherapy.
AB  - BACKGROUND: At recurrence the use of nitrosoureas is widely-used as a therapeutic
      option for glioblastoma (GBM) patients. The efficacy of fotemustine (FTM) has
      been demonstrated in phase II clinical trials; however, these papers report a
      wide range of progression-free-survival (PFS-6 m) rates, ranging from 21% to 52%.
      We investigated whether FTM could have a different response pattern in respect to
      time to adjuvant temozolomide failure, or whether specific independent risk
      factors could be responsible for the wide range of response rates observed.
      METHODS: Recurrent GBM patients have been treated with fotemustine 75-100 mg/sqm
      at day 1, 8, 15 and after 4/5 weeks of rest with 100 mg/sqm every 21 days.
      Patients were stratified in 4 groups according to time to temozolomide failure:
      before starting (B0), during the first 6 months (B1), after more than 6 months of
      therapy (B2), and after a treatment-free interval (B3). Primary endpoint was PFS
      6 m. A multivariable analysis was performed to identify whether gender, time
      after radiotherapy, second surgery and number of TMZ cycles could be independent
      predictors of the clinical benefit to FTM treatment. RESULTS: 163 recurrent GBM
      patients were included in the analysis. PFS-6 m rates for the B0, B1, B2 and B3
      groups were 25%, 28%, 31.1% and 43.8%, respectively. The probability of disease
      control was higher in patients with a longer time after radiotherapy (p = 0.0161)
      and in those who had undergone a second surgery (p = 0.0306). CONCLUSIONS: FTM is
      confirmed as a valuable therapeutic option for patients with recurrent GBM and
      was active in all study patient groups. Time after the completion of radiotherapy
      and second surgery are independent treatment-related risk factors that were
      predictive of clinical benefit.

PMID- 22583679
TI  - Spatial repellents: from discovery and development to evidence-based validation.
AB  - International public health workers are challenged by a burden of arthropod-borne
      disease that remains elevated despite best efforts in control programmes. With
      this challenge comes the opportunity to develop novel vector control paradigms to
      guide product development and programme implementation. The role of vector
      behaviour modification in disease control was first highlighted several decades
      ago but has received limited attention within the public health community. This
      paper presents current evidence highlighting the value of sub-lethal agents,
      specifically spatial repellents, and their use in global health, and identifies
      the primary challenges towards establishing a clearly defined and recommended
      role for spatial repellent products in disease control.

PMID- 22583680
TI  - "Shaping" of cell signaling via AKAP-tethered PDE4D: Probing with AKAR2-AKAP5
      biosensor.
AB  - BACKGROUND: PKA, a key regulator of cell signaling, phosphorylates a diverse and
      important array of target molecules and is spatially docked to members of the A
      kinase Anchoring Protein (AKAP) family. AKAR2 is a biosensor which yields a FRET
      signal in vivo, when phosphorylated by PKA. AKAP5, a prominent member of the AKAP
      family, docks several signaling molecules including PKA, PDE4D, as well as GPCRs,
      and is obligate for the propagation of the activation of the mitogen-activated
      protein kinase cascade from GPCRs to ERK1,2. RESULTS: Using an AKAR2-AKAP5 fusion
      "biosensor", we investigated the spatial-temporal activation of AKAP5 undergoing
      phosphorylation by PKA in response to beta-adrenergic stimulation. The pattern of
      PKA activation reported by AKAR2-AKAP5 is a more rapid and spatially distinct
      from those "sensed" by AKAR2-AKAP12. Spatial-temporal restriction of activated
      PKA by AKAP5 was found to "shape" the signaling response. Phosphatase PDE4D
      tethered to AKAP5 also later reverses within 60 s elevated intracellular cyclic
      AMP levels stimulated by beta-adrenergic agonist. AKAP12, however, fails to
      attenuate the rise in cyclic AMP over this time. Fusion of the AKAP5 PDE4D
      binding-domain to AKAP12 was found to accelerate a reversal of accumulation of
      intracellular cyclic AMP. CONCLUSION: AKAPs, which are scaffolds with tethered
      enzymes, can "shape" the temporal and spatial aspects of cell signaling.

PMID- 22583681
TI  - The effect of herbal, essential oil and chlorhexidine mouthrinse on de novo
      plaque formation.
AB  - BACKGROUND: Brushing and flossing are the most widely accepted procedures, the
      'gold standard', for controlling bacterial plaque, but these mechanical methods
      have limitations. Based on results derived from several clinical trials,
      essential oil (EO) mouthrinse (Listerine((r))) and a chlorhexidine mouthrinse
      have been accepted by ADA to be used as an adjunct to routine mechanical oral
      hygiene measures however, both of them are associated with side effects,
      therefore, the present study was undertaken to evaluate the antiplaque efficacy
      of a new herbal formulation as compared to an EO and chlorhexidine rinse.
      MATERIALS AND METHOD: The study was a single blind parallel randomized controlled
      trial involving four groups. 48 volunteers refrained from all oral hygiene
      measures for 4 days, but rinsed instead twice daily with 10 ml of a herbal (HM),
      EO, chlorhexidine (CHX) or a placebo (PL) solution. Plaque index and plaque area
      (PA) was assessed on Day 4. RESULTS: The HM and EO showed a significant
      inhibition of plaque regrowth compared to PL (P<0.001), but the lowest values of
      PI and PA were obtained with CHX. Statistically significant difference in plaque
      parameters was observed when CHX was compared to HM and EO, and HM to EO rinse.
      CONCLUSION: The new herbal mouthrinse had a promising plaque inhibitory potential
      but it not as efficacious as chlorhexidine in preventing plaque regrowth.

PMID- 22583682
TI  - Germline melanoma susceptibility and prognostic genes: a review of the
      literature.
AB  - In recent years, there have been increasing efforts to identify germline genetic
      variants that may alter melanoma susceptibility and prognosis. The findings of
      these studies have indicated the presence of rare, high-penetrance alleles with
      large effects, such as CDKN2A and CDK4, more common, moderately penetrant genes
      like MC1R, and very common, low-penetrance polymorphisms with small effects that
      are related to pigmentation, nevus count, immune responses, DNA repair,
      metabolism, and the vitamin D receptor. The study of these low-penetrance single
      nucleotide polymorphisms is relatively new; thus many of them are termed
      'candidate melanoma susceptibility or prognostic genes.' This review summarizes
      the research on germline polymorphisms that have been implicated in melanoma
      susceptibility and prognosis in order to provide a framework for additional
      studies to meet the ultimate goal of predicting a patient's risk of, and
      prognosis in, cutaneous malignant melanoma.

PMID- 22583683
TI  - Suppression of autophagy sensitizes Kupffer cells to endotoxin.
AB  - AIM:   Recent evidence suggests that protein degradation system autophagy is
      implicated in a component of innate immunity. We report here that suppression of
      autophagy in Kupffer cells due to hepatic steatosis enhances an inflammatory
      response to endotoxin. METHODS:   Kupffer cells were isolated from C57BL/6J mice
      fed chow diet (control) or high-fat diet (HFD) for 12 weeks, liver-specific
      autophagy-deficient mice (Atg7(F/F) :Mx1-Cre) and wild-type mice (Atg7(F/F) ).
      Kupffer cells were incubated with 100 ng/mL lipopolysaccharide (LPS). The
      concentration of tumor necrosis factor (TNF)-alpha in media was measured by
      enzyme-linked immunoassay. Expression of Toll-like receptor (TLR)4, IkappaB
      kinase (IKK)-alpha/beta, p38, p62 and LC3 in Kupffer cells was evaluated by
      western blot analysis. RESULTS:   Incubation with LPS increased LC3-II expression
      of Kupffer cells from control mice; however, an increase in LC3-II expression due
      to LPS was suppressed in Kupffer cells from HFD mice. Moreover, both p62
      expression and TNF-alpha production in Kupffer cells from HFD mice was higher
      than control mice. On the other hand, LPS exposure increased TNF-alpha production
      from autophagy-deficient Kupffer cells more than wild type. There was no
      significant difference in expression of TLR4 between wild and autophagy-deficient
      Kupffer cells. Nevertheless, activation of p38 or IKK in Kupffer cells due to LPS
      was augmented by autophagy deficiency. The addition of the p38 inhibitor SB203580
      attenuated TNF-alpha production in both wild and autophagy-deficient Kupffer
      cells. CONCLUSION:   These results suggest that suppression of autophagy observed
      in Kupffer cells from steatotic liver sensitizes to endotoxin. In conclusion,
      suppression of autophagy may play a pivotal role on progression of NAFLD.

PMID- 22583684
TI  - Detection of recurrent and primary acquired cholesteatoma with echo-planar
      diffusion-weighted magnetic resonance imaging.
AB  - OBJECTIVE: To evaluate the diagnostic value of echo-planar diffusion-weighted
      magnetic resonance imaging in pre-operative detection of suspected primary
      acquired, residual and/or recurrent cholesteatoma. MATERIALS AND METHODS: Fifty
      eight chronic otitis media patients with suspected cholesteatoma were thus
      evaluated two weeks pre-operatively, and divided into group one (41 patients, no
      previous surgery, suspected primary acquired cholesteatoma) and group two (17
      patients, previous surgery, scheduled 'second-look' or revision surgery for
      suspected residual or recurrent cholesteatoma). Patients' operative,
      histopathology and radiological findings were compared. RESULTS: Cholesteatoma
      was found in 63 per cent of group one patients and 58 per cent of group two
      patients at surgery. Histopathological examination of surgical specimens
      indicated that imaging accurately predicted the presence or absence of
      cholesteatoma in 90 per cent of group one (37/41; 23 true positives, 14 true
      negatives) and 76 per cent of group two (13/17; seven true positives, six true
      negatives). Three patients in both groups were false negative diagnoses and one
      patient in both groups was a false positive. The sensitivity, specificity, and
      positive and negative predictive values of echo-planar diffusion-weighted
      magnetic resonance imaging of cholesteatoma were respectively 88, 93, 95 and 82
      per cent in group one and 70, 85, 87 and 66 per cent in group two. CONCLUSION:
      Echo-planar diffusion-weighted magnetic resonance imaging is a valuable technique
      with high sensitivity and specificity for cholesteatoma imaging.

PMID- 22583685
TI  - The presence and role of bacterial quorum sensing in activated sludge.
AB  - Activated sludge used for wastewater treatment globally is composed of a high
      density microbial community of great biotechnological significance. In this study
      the presence and purpose of quorum sensing via N-acylated-l-homoserine lactones
      (AHLs) in activated sludge was explored. The presence of N-heptanoyl-l-homoserine
      lactone in organic extracts of sludge was demonstrated along with activation of a
      LuxR-based AHL monitor strain deployed in sludge, indicating AHL-mediated gene
      expression is active in sludge flocculates but not in the bulk aqueous phase.
      Bacterial isolates from activated sludge were screened for AHL production and
      expression of phenotypes commonly but not exclusively regulated by AHL-mediated
      gene transcription. N-acylated-l-homoserine lactone and exoenzyme production were
      frequently observed among the isolates. N-acylated-l-homoserine lactone addition
      to sludge upregulated chitinase activity and an AHL- and chitinase-producing
      isolate closely related to Aeromonas hydrophila was shown to respond to AHL
      addition with upregulation of chitinase activity. N-acylated-l-homoserine
      lactones produced by this strain were identified and genes ahyI/R and chiA,
      encoding AHL production and response and chitinase activity respectively, were
      sequenced. These experiments provide insight into the relationship between AHL
      mediated gene expression and exoenzyme activity in activated sludge and may
      ultimately create opportunities to improve sludge performance.

PMID- 22583686
TI  - Factors associated with attention deficit/hyperactivity disorder among US
      children: results from a national survey.
AB  - BACKGROUND: The purpose of this study was to investigate the association between
      Attention Deficit/Hyperactivity Disorder (ADHD) and various factors using a
      representative sample of US children in a comprehensive manner. This includes
      variables that have not been previously studied such as watching TV/playing video
      games, computer usage, family member's smoking, and participation in sports.
      METHODS: This was a cross-sectional study of 68,634 children, 5-17 years old,
      from the National Survey of Children's Health (NSCH, 2007-2008). We performed
      bivariate and multivariate logistic regression analyses with ADHD classification
      as the response variable and the following explanatory variables: sex, race,
      depression, anxiety, body mass index, healthcare coverage, family structure,
      socio-economic status, family members' smoking status, education, computer usage,
      watching television (TV)/playing video games, participation in sports, and
      participation in clubs/organizations. RESULTS: Approximately 10% of the sample
      was classified as having ADHD. We found depression, anxiety, healthcare coverage,
      and male sex of child to have increased odds of being diagnosed with ADHD. One of
      the salient features of this study was observing a significant association
      between ADHD and variables such as TV usage, participation in sports, two-parent
      family structure, and family members' smoking status. Obesity was not found to be
      significantly associated with ADHD, contrary to some previous studies.
      CONCLUSIONS: The current study uncovered several factors associated with ADHD at
      the national level, including some that have not been studied earlier in such a
      setting. However, we caution that due to the cross-sectional and observational
      nature of the data, a cause and effect relationship between ADHD and the
      associated factors can not be deduced from this study. Future research on ADHD
      should take into consideration these factors, preferably through a longitudinal
      study design.

PMID- 22583687
TI  - A semi-quantitative assay of overall DNA methylation status using Methyl-CpG
      binding protein (MBD1).
AB  - BACKGROUND: In mammals, DNA methylation at the 5-position of cytosine is the most
      essential epigenetic modification. Changes in the level of genome-wide DNA
      methylation (also known as overall DNA methylation) are associated with
      alterations in gene expression, thereby contributing to the phenotypic and
      physiological diversity. Current technologies for detecting overall DNA
      methylation either suffer from low sensitivity or require sophisticated
      equipment. Studies on domestic animals are hampered by the lack of complete and
      annotated genomic information. RESULTS: Here we report a rapid slot blot method
      using methyl-CpG binding protein (MBD1) to exam the level of overall DNA
      methylation in pigs and chickens. Using this rapid approach, we determined the
      methylation status in various DNA samples of a Chinese indigenous (Erhualian) and
      a Western (Large White) breed of pigs. We also chose day 18 embryos (E18) and
      newly hatched chicks (D1) of a Chinese indigenous chicken breed (Wen's yellow
      feathered broiler chicken) for genome-wide DNA methylation analysis. The results
      revealed tissue- and breed-specific differences, as well as age-dependent
      variations, in the level of overall DNA methylation. CONCLUSION: The results
      showed that the slot blot assay is a sensitive, highly specific and convenient
      method for semi-quantitative estimation of overall DNA methylation with no
      species specificity. This method does not require sophisticated equipment, such
      as high performance liquid chromatography (HPLC), or expensive technologies like
      sequencing, thus providing a useful tool for overall DNA methylation studies on
      domestic animals.

PMID- 22583688
TI  - Survey of isoniazid preventive therapy in South Africa, 2011.
AB  - SETTING: Public health facilities in South Africa. OBJECTIVE: To assess the
      implementation of isoniazid preventive treatment (IPT) in South Africa in 2011.
      DESIGN: Cross-sectional study of 50 randomly selected facilities in South Africa.
      Trained interviewers administered a standardised  questionnaire at each facility
      on aspects of IPT policy, implementation and recording and reporting. We
      calculated and compared descriptive statistics by province and facility type.
      RESULTS: Of the 49 participating sites, 35 provided IPT (71%). IPT was not
      available in any Western Cape  facility (0%), and it was available at a few
      Mpumalanga (40%) and Limpopo (20%) sites. In February 2011, 46% of eligible human
      immunodeficiency virus (HIV) infected patients at IPT-providing sites had been
      initiated on IPT. Implementation by facility type was 27% among community health
      centres.  Of all facilities with integrated tuberculosis (TB) and HIV committees
      (TB-HIV), 85% offered IPT compared to 59% of those without TB-HIV committees (P =
      0.12). Availability of the 2010 South African National IPT guidelines was
      statistically significantly associated with sites providing  IPT (84% vs. 29%, P
      = 0.006). CONCLUSION: IPT implementation in South Africa began in February 2011.
      The availability of IPT guidelines was strongly associated with IPT uptake. More
      operational studies are needed to improve IPT implementation among HIV-infected
      patients in South  Africa.

PMID- 22583689
TI  - The dietary fatty acid 10E12Z-CLA induces epiregulin expression through COX-2
      dependent PGF(2alpha) synthesis in adipocytes.
AB  - Conjugated linoleic acids (CLAs) are a group of dietary fatty acids that are
      widely marketed as weight loss supplements. The isomer responsible for this
      effect is the trans-10, cis-12 CLA (10E12Z-CLA) isomer. 10E12Z-CLA treatment
      during differentiation of 3T3-L1 adipocytes induces expression of prostaglandin
      endoperoxide synthase-2 (Cyclooxygenase-2; COX-2). This work demonstrates that
      COX-2 is also induced in fully differentiated 3T3-L1 adipocytes after a single
      treatment of 10E12Z-CLA at both the mRNA (20-40 fold) and protein level (7 fold).
      Furthermore, prostaglandin (PG)F(2alpha), but not PGE(2), is significantly
      increased 10 fold. In female BALB/c mice fed 0.5% 10E12Z-CLA for 10 days, COX-2
      was induced in uterine adipose (2 fold). In vitro, pharmacological COX-2
      inhibition did not block the effect of 10E12Z-CLA on adipocyte-specific gene
      expression although PGF(2alpha) was dose-dependently decreased. These studies
      demonstrate that PGF(2alpha) was not by itself responsible for the reduction in
      adipocyte character due to 10E12Z-CLA treatment. However, PGF(2alpha), either
      exogenously or endogenously in response to 10E12Z-CLA, increased the expression
      of the potent mitogen and epidermal growth factor (EGF) receptor (EGFR) ligand
      epiregulin in 3T3-L1 adipocytes. Blocking PGF(2alpha) signaling with the
      PGF(2alpha) receptor (FP) antagonist AL-8810 returned epiregulin mRNA levels back
      to baseline. Although this pathway is not directly responsible for adipocyte
      dependent gene expression, these results suggest that this signaling pathway may
      still have broad effect on the adipocyte and surrounding cells.

PMID- 22583690
TI  - Mechanisms of tumor necrosis factor-alpha-induced leaks in intestine epithelial
      barrier.
AB  - PURPOSE: The aim of this study was to investigate the signaling mechanisms
      surrounding changes in tight junction (TJ) and the permeability of human
      intestinal epithelial cell induced by tumor necrosis factor-alpha (TNF-alpha).
      METHODS: To confirm that TNF-alpha induces epithelial barrier hyperpermeability
      by disrupting tight junction, Caco-2 cells were exposed to TNF-alpha, and changes
      in epithelial permeability (via TER assay), F-actin dynamics (via Rhodamine
      phalloidin staining) and tight junction protein expression (via western blot)
      were monitored. Moreover, to ensure that NF-kappaB participated in the regulatory
      mechanisms, Caco-2 cells were transfected with DNMu-IkappaBalpha or control
      plasmids, the above experiments were repeated and the activation effect of TNF
      alpha on NF-kappaB was detected by luciferase reporter assays. Lastly, we took
      dominant negative plasmid and knockdown approaches to investigate the potential
      importance of the NF-kappaB/myosin light chain kinase (MLCK)/myosin light chain
      phosphorylation (pMLC) pathways in TNF-a-mediated damage. RESULT: TNF-alpha could
      cause NF-kappaB activation, F-actin rearrangement, tight junction disruption and
      barrier dysfunction. These effects were alleviated by inhibiting NF-kappaB. TNF
      alpha induced increase of MLCK transcription and MLC phosphorylation act later
      than NF-kappaB activation, which could be suppressed both by inactivating and
      deleting NF-kappaB. CONCLUSIONS: TNF-alpha induces intestinal epithelial cell
      hyperpermeability by disrupting TJs, in part through MLCK upregulation, in which
      NF-kappaB is the positive upstream regulator for MLCK.

PMID- 22583691
TI  - Alteration of intracellular secretory acute phase response proteins expressed in
      human hepatocyte induced by exposure with interleukin-6.
AB  - Interleukin-6 (IL-6) is a principal proinflammatory cytokine inducing the acute
      phase response in various tissues, including liver. Here, we adopt the FD-LC
      MS/MS method, consisting of fluorogenic derivatization (FD), separation by liquid
      chromatography (LC), and identification of proteins by LC-tandem mass
      spectrometry (MS/MS), to reveal how exposure to IL-6 alters temporally the
      intracellular secretory acute phase response (sAPR) proteins expressed in human
      hepatocytes as compared to non-exposure. Nine altered sAPR proteins were
      identified in cultures in response to IL-6. Seven of them (serum amyloid A
      protein, haptoglobin, fibrinogen alpha chain, fibrinogen beta chain, fibrinogen
      gamma chain, alpha(1)-acid glycoprotein and alpha(1)-antitrypsin) were
      significantly increased and two (beta(2)-glycoprotein 1 and transferrin) were
      significantly decreased in response to IL-6. In addition, the transmission speed
      of transferrin might be much faster than the other sAPR proteins. These results
      suggest a different molecular mechanism for protein synthesis and the secretory
      pathway among the sAPR proteins. In this study, we observed the simultaneously
      and temporally altered expression of sAPR proteins which had been induced by
      exposure to IL-6 in human hepatocytes, in contrast to previous reports, in all of
      which the proteins were tested from the time they were secreted into the medium
      from the cells.

PMID- 22583692
TI  - Cytokine and CXC chemokine expression patterns in aqueous humor of patients with
      presumed tuberculous uveitis.
AB  - Aqueous humor (AH) samples from 14 patients with presumed tuberculous uveitis
      (PTU), and 30 control patients were assayed for the proinflammatory cytokines
      interleukin IL-4, IL-12, IL-15, IL-17, interferon (IFN)-gamma, and tumor necrosis
      factor (TNF)-alpha, the immunosuppressive cytokine IL-10, and the chemokines GRO
      alpha/CXCL1, IL-8/CXCL8, MIG/CXCL9, IP-10/CXCL10 and SDF-1/CXCL12 with the use of
      a multiplex assay. Among cytokines, IL-4 and IL-12 were not detected. IL-15, IL
      17, IFN-gamma, TNF-alpha and IL-10 levels in AH were significantly higher in
      patients than in controls (p<0.001; p=0.004; p<0.001; p<0.001; p<0.001,
      respectively). Among chemokines, SDF-1 levels did not differ significantly
      between patients and controls, whereas GRO-alpha, IL-8, MIG and IP-10 levels were
      significantly higher in patients than in controls (p=0.001; p<0.001; p<0.001;
      p<0.001, respectively). Mean GRO-alpha levels in AH of PTU patients were 6-fold
      higher than IL-8 levels and mean IP-10 levels were 15-fold higher than MIG
      levels. Clinical disease activity correlated significantly with the levels of IL
      15, IFN-gamma, TNF-alpha and IP-10. Logistic regression analysis demonstrated a
      significant positive association between PTU and high levels of IFN-gamma, IL-8,
      MIG and IP-10. These data suggest that both T helper (Th) Th(1) and Th(17) cells
      are involved in PTU and that the cytokine profile is polarized toward a Th(1)
      response. GRO-alpha and IP-10 might be involved in neutrophil and activated T
      lymphocyte chemoattraction in PTU, respectively.

PMID- 22583693
TI  - Fruit and vegetable consumption among migrants in Switzerland.
AB  - OBJECTIVE: To assess the relative risk of low daily fruit and vegetable
      consumption for six large migrant groups in Switzerland. DESIGN: Cross-sectional
      health survey carried out 2007 (Swiss Health Survey) and 2010 (Swiss Migrant
      Health Survey) in Switzerland. Multinomial logistic regression models were used
      to estimate relative risk rates (RRR) of migrants relative to Swiss nationals.
      SETTING: Data obtained from representative samples of Swiss and foreign nationals
      living in Switzerland. SUBJECTS: A random sample (n =14637) of the Portuguese,
      German, Italian, Turkish, Serbian, Kosovan and Swiss permanent resident adult
      population (17-64 years old) was interviewed. RESULTS: The proportion of
      participants who adhered to the recommended fruit and vegetable consumption was
      below one-third in all study populations. Compared with Swiss nationals, the
      relative risk of low daily fruit and vegetable intake relative to recommended
      intake was higher in Turkish nationals (RRR = 2.92, 95 % CI 1.91, 4.48; P =
      0.0000) and Kosovan nationals (RRR = 4.76, 95 % CI 3.01, 7.55; P = 0.0000). The
      respective relative risks of Portuguese, Serbian, German and Italian nationals
      were not significantly different from the Swiss reference group. CONCLUSIONS:
      Initiatives for the promotion of fruit and vegetable consumption should continue
      to address the population at large. At the same time, programmes that are
      tailored to the specific needs of migrants from Turkey and Kosovo should be
      considered.

PMID- 22583694
TI  - Patients' views and experiences of pro re nata medication in acute mental health
      settings.
AB  - In the present study, we interviewed 40 patients in acute inpatient mental health
      settings regarding their experience of, and views about, receiving pro re nata
      (PRN) medication. Patient requests for PRN were primarily to relieve anxiety or
      to aid sleep, and the majority of the participants (80%) could describe a
      situation where this medication was very helpful. From the perspective of
      patients, interactions surrounding the immediate administration of PRN medication
      were inadequate, in that half of the interviewees were simply told to take the
      medication, and three-quarters said that, in their experience, formal consent was
      not commonly sought. Three-quarters of respondents came up with alternatives to
      PRN, and half wanted more information about the medication itself. These findings
      could contribute to improved nursing assessment for PRN medication need,
      administration, and monitoring.

PMID- 22583695
TI  - Increased HOX C13 expression in metastatic melanoma progression.
AB  - BACKGROUND: The process of malignant transformation, progression and metastasis
      of melanoma is not completely understood. Recently, the microarray technology has
      been used to survey transcriptional differences that might provide insight into
      the metastatic process, but the validation of changing gene expression during
      metastatic transition period is poorly investigated. A large body of literature
      has been produced on the role of the HOX genes network in tumour evolution,
      suggesting the involvement of HOX genes in several types of human cancers.
      Deregulated paralogous group 13 HOX genes expression has been detected in
      melanoma, cervical cancer and odonthogenic tumors. Among these, Hox C13 is also
      involved in the expression control of the human keratin genes hHa5 and hHa2, and
      recently it was identified as a member of human DNA replication complexes.
      METHODS: In this study, to investigate HOX C13 expression in melanoma
      progression, we have compared its expression pattern between naevi, primary
      melanoma and metastasis. In addition HOXC13 profile pattern of expression has
      been evaluated in melanoma cell lines. RESULTS: Our results show the strong and
      progressive HOX C13 overexpression in metastatic melanoma tissues and cytological
      samples compared to nevi and primary melanoma tissues and cells. CONCLUSIONS: The
      data presentated in the paper suggest a possible role of HOX C13 in metastatic
      melanoma switch.

PMID- 22583696
TI  - The SET8 H4K20 protein lysine methyltransferase has a long recognition sequence
      covering seven amino acid residues.
AB  - The SET8 histone lysine methyltransferase, which monomethylates the histone 4
      lysine 20 residue plays important roles in cell cycle control and genomic
      stability. By employing peptide arrays we have shown that it has a long
      recognition sequence motif covering seven amino acid residues, viz. R(17)-H(18)
      (R(19)KY)-K(20)-(V(21)ILFY)-(L(22)FY)-R(23). Celluspots peptide array methylation
      studies confirmed specific monomethylation of H4K20 and revealed that the
      symmetric and asymmetric methylation on R(17) of the H4 tail inhibits methylation
      on H4K20. Similarly, dimethylation of the R located at the -3 position also
      reduced methylation of p53 K382 which had been shown previously to be methylated
      by SET8. Based on the derived specificity profile, we identified 4 potential non
      histone substrate proteins. After relaxing the specificity profile, we identified
      several more candidate substrates and showed efficient methylation of 20 novel
      non-histone peptides by SET8. However, apart from H4 and p53 none of the
      identified novel peptide targets was methylated at the protein level. Since H4
      and p53 both contain the target lysine in an unstructured part of the protein, we
      conclude that the long recognition sequence of SET8 makes it difficult to
      methylate a lysine in a folded region of a protein, because amino acid side
      chains essential for recognition will be buried.

PMID- 22583697
TI  - Efficacy and safety of alogliptin added to metformin in Japanese patients with
      type 2 diabetes: a randomized, double-blind, placebo-controlled trial with an
      open-label, long-term extension study.
AB  - AIMS: To evaluate the efficacy and safety of alogliptin added to metformin versus
      metformin monotherapy in Japanese patients with type 2 diabetes who achieved
      inadequate glycaemic control on metformin (500 or 750 mg/day) + diet/exercise.
      METHODS: In a randomized, double-blind trial, 288 patients with type 2 diabetes
      mellitus T2DM received either 12.5 or 25 mg alogliptin once daily + metformin or
      placebo + metformin for 12 weeks. Thereafter, 276 patients continued on one of
      the two alogliptin dosages + metformin in an open-label extension for 40 weeks.
      The primary efficacy endpoint in the randomized, double-blind phase was the
      change in HbA1c from baseline (week 0) to the end of treatment (week 12). The
      primary endpoint during the long-term extension phase was adverse events.
      RESULTS: After 12 weeks both dosages of alogliptin + metformin produced
      significantly greater changes from baseline in HbA1c than placebo (metformin
      monotherapy: with changes in LS means - 0.55 and - 0.64% vs. 0.22%, respectively;
      p < 0.0001). Incidences of adverse effects were comparable between groups, with
      no increases in hypoglycaemia. Over 52 weeks, there were no safety or
      tolerability concerns with alogliptin when added to metformin. CONCLUSIONS:
      Alogliptin 12.5 and 25 mg once daily was safe and effective when added to
      metformin (500 or 750 mg/day) in Japanese patients with inadequately controlled
      type 2 diabetes on metformin alone.

PMID- 22583698
TI  - Morphogengineering roots: comparing mechanisms of morphogen gradient formation.
AB  - BACKGROUND: In developmental biology, there has been a recent focus on the
      robustness of morphogen gradients as possible providers of positional
      information. It was shown that functional morphogen gradients present strong
      biophysical constraints and lack of robustness to noise. Here we explore how the
      details of the mechanism which underlies the generation of a morphogen gradient
      can influence those properties. RESULTS: We contrast three gradient-generating
      mechanisms, (i) a source-decay mechanism; and (ii) a unidirectional transport
      mechanism; and (iii) a so-called reflux-loop mechanism. Focusing on the dynamics
      of the phytohormone auxin in the root, we show that only the reflux-loop
      mechanism can generate a gradient that would be adequate to supply functional
      positional information for the Arabidopsis root, for biophysically reasonable
      kinetic parameters. CONCLUSIONS: We argue that traits that differ in spatial and
      temporal time-scales can impose complex selective pressures on the mechanism of
      morphogen gradient formation used for the development of the particular organism.

PMID- 22583701
TI  - Formation of ring-opened and rearranged products of guanine: mechanisms and
      biological significance.
AB  - DNA damage by endogenous and exogenous agents is a serious concern, as the
      damaged products can affect genome integrity severely. Damage to DNA may arise
      from various factors such as DNA base modifications, strand break, inter- and
      intrastrand crosslinks, and DNA-protein crosslinks. Among these factors, DNA base
      modification is a common and important form of DNA damage that has been
      implicated in mutagenesis, carcinogenesis, and many other pathological
      conditions. Among the four DNA bases, guanine (G) has the smallest oxidation
      potential, because of which it is frequently modified by reactive species, giving
      rise to a plethora of lethal lesions. Similarly, 8-oxo-7,8-dihydroguanine (8
      oxoG), an oxidatively damaged guanine lesion, also undergoes various degradation
      reactions giving rise to several mutagenic species. The various products formed
      from reactions of G or 8-oxoG with different reactive species are mainly 2,6
      diamino-4-oxo-5-formamidopyrimidine, 2,5-diamino-4H-imidazolone, 2,2,4-triamino-5
      (2H)-oxazolone, 5-guanidino-4-nitroimidazole, guanidinohydantoin,
      spiroiminodihydantoin, cyanuric acid, parabanic acid, oxaluric acid, and urea,
      among others. These products are formed from either ring opening or ring opening
      and subsequent rearrangement. The main aim of this review is to provide a
      comprehensive overview of various possible reactions and the mechanisms involved,
      after which these ring-opened and rearranged products of guanine would be formed
      in DNA. The biological significance of oxidatively damaged products of G is also
      discussed.

PMID- 22583700
TI  - Promoter G-quadruplex sequences are targets for base oxidation and strand
      cleavage during hypoxia-induced transcription.
AB  - The G-quadruplex, a non-B DNA motif that forms in certain G-rich sequences, is
      often located near transcription start sites in growth regulatory genes. Multiple
      lines of evidence show that reactive oxygen species generated as second
      messengers during physiologic signaling target specific DNA sequences for
      oxidative base modifications. Because guanine repeats are uniquely sensitive to
      oxidative damage, and G4 sequences are known "hot spots" for genetic mutation and
      DNA translocation, we hypothesized that G4 sequences are targeted for oxidative
      base modifications in hypoxic signaling. Approximately 25% of hypoxia-regulated
      genes in pulmonary artery endothelial cells harbored G4 sequences within their
      promoters. Chromatin immunoprecipitation showed that common base oxidation
      product 8-oxoguanine was selectively introduced into G4s, in promoters of hypoxia
      up-, down-, and nonregulated genes. Additionally, base excision DNA repair (BER)
      enzymes were recruited, and transient strand breaks formed in these sequences.
      Transcription factor Sp1, constitutively bound to G4 sequences in normoxia, was
      evicted as 8-oxoguanine accumulated during hypoxic exposure. Blocking hypoxia
      induced oxidant production prevented both base modifications and decreased Sp1
      binding. These findings suggest that oxidant stress in hypoxia causes oxidative
      base modifications, recruitment of BER enzymes, and transient strand breaks in G4
      promoter sequences potentially altering G4 integrity and function.

PMID- 22583699
TI  - Regulation of innate immunity by NADPH oxidase.
AB  - NADPH oxidase is a critical regulator of both antimicrobial host defense and
      inflammation. Activated in nature by microbes and microbial-derived products, the
      phagocyte NADPH oxidase is rapidly assembled, and generates reactive oxidant
      intermediates (ROIs) in response to infectious threat. Chronic granulomatous
      disease (CGD) is an inherited disorder of the NADPH oxidase characterized by
      recurrent and severe bacterial and fungal infections, and pathology related to
      excessive inflammation. Studies in CGD patients and CGD mouse models indicate
      that NADPH oxidase plays a key role in modulating inflammation and injury that is
      distinct from its antimicrobial function. The mechanisms by which NADPH oxidase
      mediates killing of pathogens and regulation of inflammation have broad relevance
      to our understanding of normal physiological immune responses and pathological
      states, such as acute lung injury and bacterial or fungal infections.

PMID- 22583702
TI  - Heme oxygenase microsatellite polymorphism, oxidative stress, glycemic control,
      and complication development in type 2 diabetes patients.
AB  - Heme oxygenase-1 (HMOX-1) is activated by oxidative stress, and gene
      responsiveness is reportedly determined by the number of dinucleotide (GT(n))
      repeats in its highly polymorphic promoter region. "Short" (S; GT(n)<25) alleles
      reportedly associate with higher response, lower oxidative stress, lower risk of
      type 2 diabetes mellitus (type 2DM), and better glycemic control and outcome, but
      data are conflicting. We investigated GT(n) in type 2DM subjects (all ethnic
      Chinese) in relation to basal glycemic control, oxidative stress, and outcome
      during up to 9 years' follow-up. Fasting blood from 418 type 2 DM subjects was
      collected at entry for GT(n) genotyping, glycated hemoglobin, glucose, lipids,
      and biomarkers of oxidative stress and antioxidants. A subset (n=368) was
      followed for up to 9 years for incident complications or death. GT(n) genotype
      distribution was 128, 182, and 108 for, respectively, S/S, S/L, and L/L. No
      significant differences in glycemic control, lipids, or oxidative stress were
      seen across genotypes. During follow-up, 168/368 subjects developed
      complications. No association was seen with GT(n). No difference in plasma HO-1
      was seen between genotypes in a small substudy (S/S n=21 vs L/L n=23). Glycated
      hemoglobin and lymphocytic DNA damage was higher (p<0.05) at entry in the
      incident complications group. No other significant differences were seen in
      oxidative stress or antioxidants. Data do not support the postulated link between
      HMOX-1 microsatellite polymorphism and type 2 DM or the putative beneficial
      effect of the S allele on glycemic control, oxidative stress, or outcome in type
      2 DM patients, at least in this particular population.

PMID- 22583704
TI  - Artificial neural networks modeling gene-environment interaction.
AB  - BACKGROUND: Gene-environment interactions play an important role in the
      etiological pathway of complex diseases. An appropriate statistical method for
      handling a wide variety of complex situations involving interactions between
      variables is still lacking, especially when continuous variables are involved.
      The aim of this paper is to explore the ability of neural networks to model
      different structures of gene-environment interactions. A simulation study is set
      up to compare neural networks with standard logistic regression models. Eight
      different structures of gene-environment interactions are investigated. These
      structures are characterized by penetrance functions that are based on sigmoid
      functions or on combinations of linear and non-linear effects of a continuous
      environmental factor and a genetic factor with main effect or with a masking
      effect only. RESULTS: In our simulation study, neural networks are more
      successful in modeling gene-environment interactions than logistic regression
      models. This outperfomance is especially pronounced when modeling sigmoid
      penetrance functions, when distinguishing between linear and nonlinear
      components, and when modeling masking effects of the genetic factor. CONCLUSION:
      Our study shows that neural networks are a promising approach for analyzing gene
      environment interactions. Especially, if no prior knowledge of the correct nature
      of the relationship between co-variables and response variable is present, neural
      networks provide a valuable alternative to regression methods that are limited to
      the analysis of linearly separable data.

PMID- 22583703
TI  - Preserving mitochondrial function prevents the proteasomal degradation of GTP
      cyclohydrolase I.
AB  - The development of pulmonary hypertension is a common accompaniment of congenital
      heart disease (CHD) with increased pulmonary blood flow. Our recent evidence
      suggests that asymmetric dimethylarginine (ADMA)-induced mitochondrial
      dysfunction causes endothelial nitric oxide synthase (eNOS) uncoupling secondary
      to a proteasome-dependent degradation of GTP cyclohydrolase I (GCH1) that results
      in a decrease in the NOS cofactor tetrahydrobiopterin (BH(4)). Decreases in NO
      signaling are thought to be an early hallmark of endothelial dysfunction. As l
      carnitine plays an important role in maintaining mitochondrial function, in this
      study we examined the protective mechanisms and the therapeutic potential of l
      carnitine on NO signaling in pulmonary arterial endothelial cells and in a lamb
      model of CHD and increased pulmonary blood flow (Shunt). Acetyl-l-carnitine
      attenuated the ADMA-mediated proteasomal degradation of GCH1. This preservation
      was associated with a decrease in the association of GCH1 with Hsp70 and the C
      terminus of Hsp70-interacting protein (CHIP) and a decrease in its
      ubiquitination. This in turn prevented the decrease in BH(4) levels induced by
      ADMA and preserved NO signaling. Treatment of Shunt lambs with l-carnitine also
      reduced GCH1/CHIP interactions, attenuated the ubiquitination and degradation of
      GCH1, and increased BH(4) levels compared to vehicle-treated Shunt lambs. The
      increases in BH(4) were associated with decreased NOS uncoupling and enhanced NO
      generation. Thus, we conclude that L-carnitine may have a therapeutic potential
      in the treatment of pulmonary hypertension in children with CHD with increased
      pulmonary blood flow.

PMID- 22583705
TI  - Remote sensing-based time series models for malaria early warning in the
      highlands of Ethiopia.
AB  - BACKGROUND: Malaria is one of the leading public health problems in most of sub
      Saharan Africa, particularly in Ethiopia. Almost all demographic groups are at
      risk of malaria because of seasonal and unstable transmission of the disease.
      Therefore, there is a need to develop malaria early-warning systems to enhance
      public health decision making for control and prevention of malaria epidemics.
      Data from orbiting earth-observing sensors can monitor environmental risk factors
      that trigger malaria epidemics. Remotely sensed environmental indicators were
      used to examine the influences of climatic and environmental variability on
      temporal patterns of malaria cases in the Amhara region of Ethiopia. METHODS: In
      this study seasonal autoregressive integrated moving average (SARIMA) models were
      used to quantify the relationship between malaria cases and remotely sensed
      environmental variables, including rainfall, land-surface temperature (LST),
      vegetation indices (NDVI and EVI), and actual evapotranspiration (ETa) with lags
      ranging from one to three months. Predictions from the best model with
      environmental variables were compared to the actual observations from the last 12
      months of the time series. RESULTS: Malaria cases exhibited positive associations
      with LST at a lag of one month and positive associations with indicators of
      moisture (rainfall, EVI and ETa) at lags from one to three months. SARIMA models
      that included these environmental covariates had better fits and more accurate
      predictions, as evidenced by lower AIC and RMSE values, than models without
      environmental covariates. CONCLUSIONS: Malaria risk indicators such as satellite
      based rainfall estimates, LST, EVI, and ETa exhibited significant lagged
      associations with malaria cases in the Amhara region and improved model fit and
      prediction accuracy. These variables can be monitored frequently and extensively
      across large geographic areas using data from earth-observing sensors to support
      public health decisions.

PMID- 22583706
TI  - Complications of radiofrequency ablation for hepatocellular carcinoma in a
      multicenter study: An analysis of 16 346 treated nodules in 13 283 patients.
AB  - AIM:   We surveyed multiple centers to identify types and frequency of
      complications and mortality rate associated with radiofrequency ablation (RFA) of
      hepatocellular carcinoma (HCC). METHODS:   We distributed a questionnaire
      developed by members of the Chugoku-Shikoku Society for the Local Ablation
      Therapy of Hepatocellular Carcinoma to 20 centers and analyzed types and
      frequency of complications and mortality rate. RESULTS:   In total, 16 346
      nodules were treated in 13 283 patients between January 1999 and November 2010.
      Five patients (0.038%) died: two from intraperitoneal hemorrhage, and one each
      from hemothorax, severe acute pancreatitis and perforation of the colon. In 16
      346 treated nodules, 579 complications (3.54%) were observed, including 78
      hemorrhages (0.477%), 276 hepatic injuries (1.69%), 113 extrahepatic organ
      injuries (0.691%) and 27 tumor progressions (0.17%). The centers that treated a
      large number of nodules and performed RFA modifications, such as use of
      artificial ascites, artificial pleural effusion and bile duct cooling, had low
      complication rates. CONCLUSION:   This study confirmed that RFA is a low-risk
      treatment for HCC and that sufficient experience and technical skill can reduce
      complications.

PMID- 22583707
TI  - An assessment of periodontal health in patients with schizophrenia and taking
      antipsychotic medication.
AB  - BACKGROUND AND OBJECTIVE: Severe periodontal disease is prevalent among patients
      with schizophrenia and is caused by the side effect of their medication, poor
      dental hygiene and smoking. The objective of this study was to evaluate whether
      the rate of periodontal disease could be modulated by changing the salivary flow
      rate (SFR) because of the use of antipsychotic medications in patients with
      schizophrenia. METHODS: Group A (n=33) included patients who used medications
      that may cause xerostomia, or dry mouth and Group B (n=20) included patients who
      used medications that may cause sialorrhea, an excessive secretion of saliva. The
      participants' periodontal status was assessed using the plaque index (PI),
      assessing bleeding on probing (BoP), probing pocket depth (PPD) and clinical
      attachment levels (CAL). RESULTS: The mean of PI and BoP was significantly higher
      in Group A than in Group B (P<0.001), but the PPD, CAL and decayed, missing and
      filled teeth (DMFT) scores were not significantly different in the two groups
      according to the statistical results (P>0.05). CONCLUSIONS: The researcher
      concluded that there is a high risk of periodontal disease among patients with
      schizophrenia, and there is an even higher risk of periodontal disease induced by
      medication that increased SFR. Preventive dental protocol should be increased
      during the dental health care of this disadvantaged patient group.

PMID- 22583708
TI  - Cost-effectiveness of family psychoeducation to prevent relapse in major
      depression: results from a randomized controlled trial.
AB  - BACKGROUND: Family psychoeducation is a relatively simple and straightforward
      intervention whose prophylactic effectiveness and cost-effectiveness is well
      established for schizophrenia. We have recently demonstrated its effectiveness
      for unipolar depression, but its cost-effectiveness has never been examined. We
      hereby report a cost-effectiveness analysis alongside a randomized controlled
      trial in order to assess its cost-effectiveness for preventing relapse/recurrence
      in depression. METHODS: Fifty-seven patients diagnosed with major depression and
      undergoing its maintenance treatment, and their primary family members were
      randomized to treatment as usual (TAU) only or to TAU plus family
      psychoeducation, which consisted of four 2-hour multiple-family sessions
      consisting of didactic lectures about depression (30 minutes) and group
      discussion and problem solving (60-90 minutes). The economic analyses were
      undertaken from the perspective of the National Health Insurance (NHI), assuming
      the most reasonable price of US$50 per psychoeducation session per patient. The
      main outcome measures included relapse-free days and direct costs to the NHI.
      RESULTS: The intervention group enjoyed 272 (SD: 7.1) relapse-free days, while
      the control group spent 214 (SD: 90.8) relapse-free days (Cox proportional hazard
      ratio=0.17, 95%CI: 0.04 to 0.75, p=0.002). Cost-effectiveness acceptability
      curves suggested that the family psychoeducation has 90% or more chances of being
      cost-effective if the decision-maker is prepared to pay US$20 for one additional
      relapse-free day. This cost-effectiveness finding was robust when the price for
      family psychoeducation ranged between 50% to 150% of the baseline scenario in
      sensitivity analyses. If a relapse-free day is considered to be worth $30 or
      more, all the pricing scenarios have a close to 100% probability of being cost
      effective. CONCLUSION: Family psychoeducation is effective in the relapse
      prevention of depression and is highly likely to be cost-effective if a relapse
      free day is valued as US$20 or more. TRIAL REGISTRATION: UMIN-CTR
      (UMIN000005555).

PMID- 22583709
TI  - The unsolicited ominous diagnosis: legal, moral, and ethical considerations.

PMID- 22583710
TI  - Calcinosis cutis: an additional therapy to consider.

PMID- 22583711
TI  - Evidence for fractional laser treatment in the improvement of cutaneous scars.

PMID- 22583714
TI  - Stability of sunscreens and sunblocks following exposure to extreme temperatures.

PMID- 22583715
TI  - The infra-auricular fissure: a bedside marker of disease severity in patients
      with atopic dermatitis.

PMID- 22583716
TI  - Refusal of shingles vaccine: implications for public health.

PMID- 22583717
TI  - Association between pediatric psoriasis and the metabolic syndrome.

PMID- 22583718
TI  - Lipodermatosclerosis: improvement noted with hydroxychloroquine and
      pentoxifylline.

PMID- 22583719
TI  - Dermatophytoma: description of 7 cases.

PMID- 22583720
TI  - Human papillomavirus-related genital disease in the immunocompromised host: Part
      I.
AB  - Human papillomavirus (HPV) is responsible for common condyloma acuminata and a
      number of premalignant and malignant anogenital lesions. These conditions are of
      particular concern in immunocompromised individuals who have higher risk of
      malignant transformation and are more difficult to treat. This is part I of a two
      part review that will highlight the cutaneous features of condyloma acuminata and
      vaginal, vulvar, penile, and anal intraepithelial neoplasias, with an emphasis on
      presentation of these HPV-mediated diseases in the immunocompromised host.
      Counseling patients about these conditions requires a thorough understanding of
      the epidemiology, natural history of HPV, transmission and infectivity, risk of
      malignancy, and the role of the host immune response in clearing HPV lesions.
      Part II will provide an updated review of available treatments, with a focus on
      recent advances and the challenges faced in successfully treating HPV lesions in
      immunocompromised patients.

PMID- 22583721
TI  - Human papillomavirus-related genital disease in the immunocompromised host: Part
      II.
AB  - Human papillomavirus is responsible for common condyloma acuminata and a number
      of premalignant and malignant anogenital lesions. The immunocompromised
      population is at particular risk because of a higher incidence of malignant
      transformation. Lesions in this population may prove refractory to standard
      treatment. This is part II of a two-part review that will discuss the treatment
      of condyloma acuminata and vaginal, vulvar, penile, and anal intraepithelial
      neoplasias. This article will provide an updated review of available treatments,
      with a focus on recent advances and the challenges faced in successfully treating
      human papillomavirus lesions in the immunocompromised host.

PMID- 22583724
TI  - Chemical leukoderma after the application of a transdermal methylphenidate patch.

PMID- 22583725
TI  - Blastic plasmacytoid dendritic cell neoplasm in a child.

PMID- 22583726
TI  - Mycosis fungoides-associated follicular mucinosis after bone-marrow
      transplantation.

PMID- 22583727
TI  - Onychopapilloma presenting as longitudinal melanonychia.

PMID- 22583728
TI  - Pemphigus foliaceus clearance status postmyomectomy for an enlarged infarcted
      subserous uterine fibroid.

PMID- 22583729
TI  - Nodular scleroderma presenting as multiple spontaneous keloidal scars.

PMID- 22583730
TI  - Multiple cutaneous metastatic chordomas from the sacrum.

PMID- 22583731
TI  - Mycobacterium celatum skin infection with sporotrichoid spread in an HIV-negative
      immunocompromised man.

PMID- 22583732
TI  - Successful treatment of lamotrigine-associated drug hypersensitivity syndrome
      with intravenous IgG.

PMID- 22583733
TI  - Galli-Galli disease is an acantholytic variant of Dowling-Degos disease:
      additional genetic evidence in a German family.

PMID- 22583734
TI  - A case of rapid improvement of severe psoriasis during molecular-targeted therapy
      using an epidermal growth factor receptor tyrosine kinase inhibitor for
      metastatic lung adenocarcinoma.

PMID- 22583735
TI  - Histone modifications as a pathogenic mechanism of colorectal tumorigenesis.
AB  - Epigenetic regulation of gene expression has provided colorectal cancer (CRC)
      pathogenesis with an additional trait during the past decade. In particular,
      histone post-translational modifications set up a major component of this process
      dictating chromatin status and recruiting non-histone proteins in complexes
      formed to "handle DNA". In CRC, histone marks of aberrant acetylation and
      methylation levels on specific residues have been revealed, along with a plethora
      of deregulated enzymes that catalyze these reactions. Mutations, deletions or
      altered expression patterns transform the function of several histone-modifying
      proteins, further supporting the crucial role of epigenetic effectors in CRC
      oncogenesis, being closely associated to inactivation of tumor suppressor genes.
      Elucidation of the biochemical basis of these new tumorigenic mechanisms allows
      novel potential prognostic factors to come into play. Moreover, the detection of
      these changes even in early stages of the multistep CRC process, along with the
      reversible nature of these mechanisms and the technical capability to detect such
      alterations in cancer cells, places this group of covalent modifications as a
      further potential asset for clinical diagnosis or treatment of CRC. This review
      underlines the biochemistry of histone modifications and the potential regulatory
      role of histone-modifying proteins in CRC pathogenesis, to date. Furthermore, the
      underlying mechanisms of the emerging epigenetic interplay along with the
      chemical compounds that are candidates for clinical use are discussed, offering
      new insights for further investigation of key histone enzymes and new therapeutic
      targets.

PMID- 22583736
TI  - "They don't just disappear": acknowledging death in the long-term care setting.
AB  - OBJECTIVE: The purpose of this study was to describe the value of a formal room
      blessing ritual held within a long-term care facility, from the perspectives of
      staff, residents, and family members. METHOD: A qualitative research study
      involving interviews with staff, residents, and family members was conducted to
      examine the perceived value of a room blessing ritual. RESULTS: Twenty-four room
      blessing attendees participated in the study (nine staff, eight residents, and
      seven family members). Attendees felt that the room blessing provided an
      opportunity to formally acknowledge the death of the resident and their grief;
      the majority felt that this was a positive experience and that it provided an
      element of closure. Staff members and residents expressed their appreciation for
      the opportunity to connect with family members of the deceased to express their
      condolences during the ritual. Participants also identified the inclusivity of
      the ritual (i.e., an open invitation to all staff, residents, and family members)
      as a positive aspect that served as a reminder that others shared in their grief.
      Staff members felt that blessing the room for the new resident was an important
      component of the ritual, helping to bridge the gap between mourning and welcoming
      a new person. Staff, residents, and family members felt that the room blessing
      positively reflected the mission and values of the facility. The most highly
      valued aspect of the ritual for all attendees was the sharing of stories about
      the deceased to celebrate that person's life. SIGNIFICANCE OF RESULTS: Long-term
      care facilities need to recognize that formal supports to manage the bereavement
      needs of staff and residents, such as a room blessing ritual, should be
      incorporated into their model for managing end-of-life care, given the
      relationship between the emotional health of staff and the quality of care
      provided for residents.

PMID- 22583737
TI  - Validation and characterization of Citrus sinensis microRNAs and their target
      genes.
AB  - BACKGROUND: MicroRNAs play vital role in plant growth and development by
      changeable expression of their target genes with most plant microRNAs having
      perfect or near-perfect complementarities with their target genes but miRNAs in
      Citrus sinensis (csi-miRNAs) and their function have not been widely studied.
      FINDINGS: In this study, 15 potential microRNAs in Citrus sinensis (csi-miRNAs)
      were identified and bioinformatically validated using miR-RACE, a newly developed
      method for determination of miRNAs prediction computationally. The expression of
      these fifteen C. sinensis miRNAs can be detected in leaves, stems, flowers and
      fruits of C. sinensis by QRT-PCR with some of them showed tissue-specific
      expression. Six potential target genes were identified for six csi-miRNAs and
      also experimentally verified by Poly (A) polymerase -mediated 3' rapid
      amplification of cDNA ends (PPM-RACE) and RNA ligase-mediated 5' rapid
      amplification of cDNA ends (RLM-RACE) which mapped the cleavage site of target
      mRNAs and detected expression patterns of cleaved fragments that indicate the
      regulatory function of the miRNAs on their target genes. CONCLUSIONS: Our results
      confirm that small RNA-mediated regulation whereby all csi-miRNAs regulate their
      target genes by degradation.

PMID- 22583738
TI  - Bulk movement included in multi-channel mechanomyography: similarity between
      mechanomyography of resting muscle and that of contracting muscle.
AB  - Although mechanomyography (MMG) reflects local vibrations from contracting muscle
      fibers, it also includes bulk movement: deformation in global soft tissue around
      measuring points. To distinguish between them, we compared the multi-channel MMG
      of resting muscle, which dominantly reflected the bulk movement caused by
      arterial pulsations, to that of the contracting muscle. The MMG signals were
      measured at five points around the upper arms of 10 male subjects during resting
      and during isometric ramp contraction from 5% to 85% of maximal voluntary
      contraction (MVC) of the biceps brachii muscle. The characteristics of bulk
      movement were defined as the amplitude distribution and phase relation among the
      five MMG signals. The bulk movement characteristics during the rest state were
      not necessarily the same among the subjects. However, below 30 Hz, each subject's
      characteristics remained the same from the rest state (0% MVC) to the contracting
      state (80% MVC), at which the bulk movement mainly originates from muscle
      contraction activity. Results show that the MMG of the low frequency domain (<30
      Hz) includes bulk movement depending on the mechanical deformation
      characteristics of each subject's body, for a wide range of muscle contraction
      intensities.

PMID- 22583739
TI  - Ocular and cervical vestibular evoked myogenic potentials in response to bone
      conducted vibration in patients with probable inferior vestibular neuritis.
AB  - BACKGROUND AND AIMS: Previous evidence shows that the n10 component of the ocular
      vestibular evoked myogenic potential indicates utricular function, while the p13
      component of the cervical vestibular evoked myogenic potential indicates saccular
      function. This study aimed to assess the possibility of differential utricular
      and saccular function testing in the clinic, and whether loss of saccular
      function affects utricular response. METHODS: Following vibration conduction from
      the mid-forehead at the hairline, the ocular n10 component was recorded by
      surface electromyograph electrodes beneath both eyes, while the cervical p13-n23
      component was recorded by surface electrodes over the tensed sternocleidomastoid
      muscles. RESULTS: Fifty-nine patients were diagnosed with probable inferior
      vestibular neuritis, as their cervical p13-n23 component was asymmetrical (i.e.
      reduced or absent on the ipsilesional side), while their ocular n10 component was
      symmetrical (i.e. normal beneath the contralesional eye). CONCLUSION: The sense
      organ responsible for the cervical and the ocular vestibular evoked myogenic
      potentials cannot be the same, as one response was normal while the other was
      not. Reduced or absent saccular function has no detectable effect on the ocular
      n10 component. On vibration stimulation, the ocular n10 component indicates
      utricular function and the cervical p13-n23 component indicates saccular
      function.

PMID- 22583740
TI  - Magnetic resonance imaging in neonates with total asphyxia.
AB  - Magnetic resonance (MR) findings in cases of total asphyxia, whose lesions are
      mainly in the brainstem and deep nuclei, have not been clarified. In this study,
      we investigated MR images in neonates with total asphyxia. MR images of six
      infants (three males and three females; gestational age, 35-39 weeks; birth
      weights, 1880-3572 g) with total asphyxia were examined. In all subjects,
      neonatal cortical MR lesions were limited to the hippocampus with highlighting on
      T1-weighted imaging (T1-WI). The neonatal MR lesions of the cerebral white matter
      were limited to the white matter between the insula and putamen in four infants,
      and were diffusely involved in two infants. The ventral lateral nucleus of the
      thalamus was hyperintense on T1-WI in all of the subjects. Other nuclei in the
      thalamus, the globus pallidus and the putamen were involved in neonatal MR images
      of all subjects. High intensity areas on T2- weighted imaging were observed at
      the dorsal areas in the midbrain, pons and medulla oblongata in all or most of
      the subjects at the neonatal period. Also, high intensity areas on T1-WI were
      observed in the tegmentum of the pons and the midbrain in five cases. Neonates
      with total asphyxia had lesions mainly in the tegmentem of the brainstem,
      thalamus, putamen and globus palludus. Some of the infants had extensive lesions
      of the white matter.

PMID- 22583742
TI  - Safe campus using wireless managed automated external defibrillator (AED).

PMID- 22583741
TI  - Research evidence uptake in a developing country: a survey of attitudes,
      education and self-efficacy, engagement, and barriers among physical therapists
      in the Philippines.
AB  - RATIONALE AND OBJECTIVE: Use of evidence from systematic research is critical in
      evidence-based physical therapy, yet this has not been described well in
      developing countries where its purported benefits are most needed. This study
      explored research evidence uptake among physical therapists in the Philippines.
      METHOD: A probability survey of practitioners in tertiary hospitals in the
      Philippines' National Capital Region was conducted. RESULTS: Of the 188
      questionnaires distributed, 152 were returned for an 81% response rate. Positive
      attitudes were consistently reported (78-93%), although education and self
      efficacy related to key dimensions such as searching, appraising and integrating
      evidence were varied (53-82%). Less than 50% reported using research evidence
      routinely in five of six dimensions of clinical practice, except in selecting
      treatments (53%). Textbooks, own observations and expert opinion were
      consistently relied upon (74-96%) while average-month approximations of
      engagement in relevant activities such as searching, reading, appraising and
      applying research literature were low (10-18%). Participants faced a number of
      barriers such as lack of time, resources, skills, access to research literature,
      supporting administrative policies, in-service training and authority in decision
      making. CONCLUSIONS: The low research evidence uptake and heavy reliance on
      potentially biased evidence sources strongly indicate the need for effective
      professional education for practitioners to address current barriers as well as
      early intensive undergraduate education for students to ensure adequate
      preparation on being effective research evidence consumers. Given the profile of
      Filipino physical therapists, alternatives to 'from scratch' evidence searching
      and appraisal are required if widespread uptake is envisaged.

PMID- 22583743
TI  - Validation of the Treatment Satisfaction Questionnaire for Medication in patients
      with cystic fibrosis.
AB  - BACKGROUND: Our objective was to confirm the measurement properties of the
      Treatment Satisfaction Questionnaire with Medication (TQSM) in patients with
      cystic fibrosis (CF) receiving inhaled antibiotics. METHODS: The TSQM was
      included in the EAGER study, a clinical trial comparing a nebulized and a dry
      powder device for inhaled tobramycin in a CF population with chronic Pseudomonas
      aeruginosa (Pa) lung infection, aged 6 years and above (N=553). Reliability and
      validity of the questionnaire were investigated using Cronbach's alpha and
      multitrait-multimethod approach. RESULTS: The TSQM demonstrated very good
      reliability and construct validity: all Cronbach's alpha were above 0.86 and all
      items met the convergent and discriminant validity criteria. In multivariate
      regressions, higher patient satisfaction and lower perceived impact of side
      effects were associated with better treatment compliance. CONCLUSIONS: The TSQM
      showed very good measurement properties that strongly support its use to assess
      satisfaction of patients with CF taking inhaled antibiotics.

PMID- 22583744
TI  - Identification of avian W-linked contigs by short-read sequencing.
AB  - BACKGROUND: The female-specific W chromosomes and male-specific Y chromosomes
      have proven difficult to assemble with whole-genome shotgun methods, creating a
      demand for new approaches to identify sequence contigs specific to these sex
      chromosomes. Here, we develop and apply a novel method for identifying sequences
      that are W-specific. RESULTS: Using the Illumina Genome Analyzer, we generated
      sequence reads from a male domestic chicken (ZZ) and mapped them to the existing
      female (ZW) genome sequence. This method allowed us to identify segments of the
      female genome that are underrepresented in the male genome and are therefore
      likely to be female specific. We developed a Bayesian classifier to automate the
      calling of W-linked contigs and successfully identified more than 60 novel W
      specific sequences. CONCLUSIONS: Our classifier can be applied to improve
      heterogametic whole-genome shotgun assemblies of the W or Y chromosome of any
      organism. This study greatly improves our knowledge of the W chromosome and will
      enhance future studies of avian sex determination and sex chromosome evolution.

PMID- 22583745
TI  - The development and application of a single-cell biosensor for the detection of l
      methionine and branched-chain amino acids.
AB  - The detection and quantification of specific metabolites in single bacterial
      cells is a major goal for industrial biotechnology. We have developed a biosensor
      based on the transcriptional regulator Lrp that detects intracellular l
      methionine and branched-chain amino acids in Corynebacterium glutamicum. In
      assays, fluorescence output showed a linear relationship with cytoplasmic
      concentrations of the effector amino acids. In increasing order, the affinity of
      Lrp for the amino acids is l-valine, l-isoleucine, l-leucine and l-methionine.
      The sensor was applied for online monitoring and analysis of cell-to-cell
      variability of l-valine production by the pyruvate dehydrogenase-deficient C.
      glutamicum strain DeltaaceE. Finally, the sensor system was successfully used in
      a high-throughput (HT) FACS screen for the isolation of amino acid-producing
      mutants after random mutagenesis of a non-producing wild type strain. These
      applications illustrate how one of nature's sensor devices - transcriptional
      regulators - can be used for the analysis, directed evolution and HT screening
      for microbial strain development.

PMID- 22583746
TI  - Independent association of younger age with hemoptysis in adults with pulmonary
      tuberculosis.
AB  - BACKGROUND: The risk factors for mild to moderate hemoptysis in patients with
      pulmonary tuberculosis (PTB) are not entirely clear. OBJECTIVE: To evaluate the
      independent association of risk factors with the occurrence of hemoptysis in PTB
      patients. DESIGN: Cross-sectional study  of adult patients newly diagnosed with
      microbiologically proven PTB in a New York City hospital. Patients were
      categorized into subjects with and without hemoptysis and compared using
      univariate analysis. Independent associations of variables with hemoptysis were
      estimated using multivariate  logistic regression. RESULTS: Of 194 subjects with
      PTB, 44 (23%) had hemoptysis. In univariate analysis, subjects with hemoptysis
      were significantly younger (P = 0.003), and more likely to be undocumented
      foreign-born (P = 0.038) compared to subjects without hemoptysis. In 
      multivariate analysis, only younger age was independently associated with
      hemoptysis. This association was significant for a continuous decrease in age per
      year, or per decade (adjusted OR 1.59, P = 0.003). CONCLUSIONS: Younger age is an
      independent risk factor for hemoptysis in  PTB. It is conceivable that a stronger
      inflammatory response in younger than in older age could contribute to pulmonary
      pathogenesis and injury in PTB.

PMID- 22583747
TI  - Polarized recombination of acoustically transported carriers in GaAs nanowires.
AB  - : The oscillating piezoelectric field of a surface acoustic wave (SAW) is
      employed to transport photoexcited electrons and holes in GaAs nanowires
      deposited on a SAW delay line on a LiNbO3 crystal. The carriers generated in the
      nanowire by a focused light spot are acoustically transferred to a second
      location where they recombine. We show that the recombination of the transported
      carriers occurs in a zinc blende section on top of the predominant wurtzite
      nanowire. This allows contactless control of the linear polarized emission by
      SAWs which is governed by the crystal structure. Additional polarization-resolved
      photoluminescence measurements were performed to investigate spin conservation
      during transport.

PMID- 22583748
TI  - Equine subepithelial keratomycosis.
AB  - OBJECTIVE: To describe clinical findings in equine subepithelial keratomycosis
      (SEK). DESIGN: Retrospective medical records study. ANIMALS STUDIED: Medical
      records of horses that had subepithelial keratomycosis (SEK) at the University of
      Florida Veterinary Medical Center from 2007 to 2011 were reviewed. PROCEDURES:
      Data collected from the medical records included signalment, clinical
      descriptions of ocular lesions, diagnostic techniques, and therapeutic outcomes.
      RESULTS: Twenty-one horses, consisting of three Quarter horse geldings, two
      Morgan geldings, one Morgan mare, two Arabian mares, three Arabian geldings, two
      warm blood mares, two warm blood geldings, two Thoroughbred geldings, one
      Thoroughbred mare, one Appaloosa mare, one Holsteiner gelding, and one Holsteiner
      mare with SEK were identified. Multifocal punctate and/or geographic patterns of
      subepithelial opacification were present in all eyes. Intermittent phases of weak
      fluorescein and/or rose Bengal dye were found in 16 eyes. Clinical signs of
      iridocyclitis were absent in all eyes. Cytologic confirmation of fungi was found
      in ten cases, Candida was cultured from one eye, and Aspergillus cultured in
      three eyes. Nineteen of 21 eyes with SEK resolved when topical antifungal therapy
      was initiated. Two of the 19 responding eyes recurred and required additional
      therapy, and two other eyes progressed to ulcerative keratomycosis. CONCLUSIONS:
      This is the first clinical report of a subtle form of keratomycosis in the horse.
      Subepithelial keratomycosis may be a distinct clinical entity or represent a
      continuum in the described forms of equine keratomycosis.

PMID- 22583749
TI  - Citation analysis of mental health nursing journals: how should we rank thee?
AB  - The journal impact factor (JIF), and how best to rate the performance of a
      journal and the articles they contain, are areas of great debate. The aim of this
      paper was to assess various ranking methods of journal quality for mental health
      nursing journals, and to list the top 10 articles that have received the most
      number of citations to date. Seven mental health nursing journals were chosen for
      the analysis of citations they received in 2010, as well as their current impact
      factors from two sources, and other data for ranking purposes. There was very
      little difference in the top four mental health nursing journals and their
      overall rankings when combining various bibliometric indicators. That said, the
      International Journal of Mental Health Nursing is currently the highest ranked
      mental health nursing journal based on JIF, but publishes fewer articles per year
      compared to other journals. Overall, very few articles received 50 or more
      citations. This study shows that researchers need to consider more than one
      ranking method when deciding where to send or publish their research.

PMID- 22583750
TI  - Organizational structure and the periphery of the gene regulatory network in B
      cell lymphoma.
AB  - BACKGROUND: The physical periphery of a biological cell is mainly described by
      signaling pathways which are triggered by transmembrane proteins and receptors
      that are sentinels to control the whole gene regulatory network of a cell.
      However, our current knowledge about the gene regulatory mechanisms that are
      governed by extracellular signals is severely limited. RESULTS: The purpose of
      this paper is three fold. First, we infer a gene regulatory network from a large
      scale B-cell lymphoma expression data set using the C3NET algorithm. Second, we
      provide a functional and structural analysis of the largest connected component
      of this network, revealing that this network component corresponds to the
      peripheral region of a cell. Third, we analyze the hierarchical organization of
      network components of the whole inferred B-cell gene regulatory network by
      introducing a new approach which exploits the variability within the data as well
      as the inferential characteristics of C3NET. As a result, we find a functional
      bisection of the network corresponding to different cellular components.
      CONCLUSIONS: Overall, our study allows to highlight the peripheral gene
      regulatory network of B-cells and shows that it is centered around hub
      transmembrane proteins located at the physical periphery of the cell. In
      addition, we identify a variety of novel pathological transmembrane proteins such
      as ion channel complexes and signaling receptors in B-cell lymphoma.

PMID- 22583751
TI  - Improved methods for haemozoin quantification in tissues yield organ-and parasite
      specific information in malaria-infected mice.
AB  - BACKGROUND: Despite intensive research, malaria remains a major health concern
      for non-immune residents and travelers in malaria-endemic regions. Efficient
      adjunctive therapies against life-threatening complications such as severe
      malarial anaemia, encephalopathy, placental malaria or respiratory problems are
      still lacking. Therefore, new insights into the pathogenesis of severe malaria
      are imperative. Haemozoin (Hz) or malaria pigment is produced during intra
      erythrocytic parasite replication, released in the circulation after schizont
      rupture and accumulates inside multiple organs. Many in vitro and ex vivo
      immunomodulating effects are described for Hz but in vivo data are limited. This
      study aimed to improve methods for Hz quantification in tissues and to
      investigate the accumulation of Hz in different organs from mice infected with
      Plasmodium parasites with a varying degree of virulence. METHODS: An improved
      method for extraction of Hz from tissues was elaborated and coupled to an
      optimized, quantitative, microtiter plate-based luminescence assay with a high
      sensitivity. In addition, a technique for measuring Hz by semi-quantitative
      densitometry, applicable on transmitted light images, was developed. The methods
      were applied to measure Hz in various organs of C57BL/6 J mice infected with
      Plasmodium berghei ANKA, P. berghei NK65 or Plasmodium chabaudi AS. The used
      statistical methods were the Mann-Whitney U test and Pearsons correlation
      analysis. RESULTS: Most Hz was detected in livers and spleens, lower levels in
      lungs and kidneys, whereas sub-nanomolar amounts were observed in brains and
      hearts from infected mice, irrespectively of the parasite strain used.
      Furthermore, total Hz contents correlated with peripheral parasitaemia and were
      significantly higher in mice with a lethal P. berghei ANKA or P. berghei NK65
      infection than in mice with a self-resolving P. chabaudi AS-infection, despite
      similar peripheral parasitaemia levels. CONCLUSIONS: The developed techniques
      were useful to quantify Hz in different organs with a high reproducibility and
      sensitivity. An organ-specific Hz deposition pattern was found and was
      independent of the parasite strain used. Highest Hz levels were identified in
      mice infected with lethal parasite strains suggesting that Hz accumulation in
      tissues is associated with malaria-related mortality.

PMID- 22583752
TI  - High intensity focused ultrasound ablation of goat liver in vivo: Pathologic
      changes of portal vein and the "heat-sink" effect.
AB  - The purpose of this study was to evaluate pathological changes of the portal vein
      (PV) and the effects on main branches of the hepatic PV during HIFU (high
      intensity focused ultrasound) sonication when liver tissue adjacent to the main
      branches of hepatic PV was ablated. Normal liver tissue at 0mm, 5mm, 10mm away
      from the hepatic portal vein in 50 healthy goats was ablated with magnetic
      resonance image-guided HIFU (MRgHIFU). MRI showed a non-perfusion region at the
      target area but did not show any significant changes of the PV immediately after
      HIFU. The histological examination 1 day after HIFU showed coagulative necrosis
      at the target area, revealed deep-dyed swelling collagen (CS) fibers and vessel
      wall fracture (VWF) in the PV adjacent to the target area; however, no CS or VWF
      was observed in the PV 1 week after HIFU ablation. The energy required to ablate
      the foci at 0mm was 21% more than that at 10mm from the PV (p<0.05); the energy
      needed to ablate foci 5mm away from the PV was 10% more than that at 10mm from
      the PV (p<0.05). We concluded that minor injury of the hepatic portal vein may
      occur when ablating the adjacent liver tissue, and the acoustic energy deposition
      is related to the distance to the portal vein.

PMID- 22583755
TI  - When combat prevents PTSD symptoms--results from a survey with former child
      soldiers in Northern Uganda.
AB  - BACKGROUND: Human beings from time immemorial have eradicated neighbouring
      tribes, languages, religions, and cultures. In war and crisis, the cumulative
      exposure to traumatic stress constitutes a predictor of the development of post
      traumatic stress disorder (PTSD). However, homicide has evolved as a profitable
      strategy in man, leading to greater reproductive success. Thus, an evolutionary
      advantage of perpetrating violence would be eliminated if the exposure to
      aggressive acts would traumatize the perpetrator. We argue that perpetrating
      violence could actually 'immunize' a person against adverse effects of traumatic
      stressors, significantly reducing the risk of developing PTSD. METHODS: We
      surveyed 42 former child soldiers in Northern Uganda that have all been abducted
      by the Lord Resistance Army (LRA) as well as 41 non-abducted controls. RESULTS:
      Linear regression analyses revealed a dose-response effect between the exposure
      to traumatic events and the Posttraumatic Diagnostic Scale (PDS) sum score.
      However, the vulnerability to develop trauma related symptoms was reduced in
      those with higher scores on the Appetitive Aggression Scale (AAS). This effect
      was more pronounced in the formerly abducted group. CONCLUSIONS: We conclude that
      attraction to aggression when being exposed to the victim's struggling can lead
      to a substantial risk-reduction for developing PTSD.

PMID- 22583754
TI  - Identification of rutin deglycosylated metabolites produced by human intestinal
      bacteria using UPLC-Q-TOF/MS.
AB  - In this paper, rutin was metabolized by human intestinal bacteria and five
      isolated strains including Bacillus sp. 52, Bacteroides sp. 45, 42, 22 and
      Veillonella sp. 32, the metabolites were identified using ultra performance
      liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC-Q
      TOF/MS). As a result, Bacillus sp. 52 and Bacteroides sp. 45 could metabolize
      rutin to quercetin 3-O-glucoside and leucocyanidin. Bacteroides sp. 42 and
      Veillonella sp. 32 could convert rutin to leucocyanidin. Bacteroides sp. 22 could
      hydrolyze rutin to quercetin-3-O-glucoside. In order to further explain the
      metabolism pathway of rutin, the beta-D-glucosidase and alpha-L-rhamnosidase
      activities of five strains were determined. Bacteroides sp. 22 could produce
      alpha-L-rhamnosidase but did not produce beta-D-glucosidase or beta-D-glucosidase
      activity was too low to be detected. The other four strains all demonstrated
      alpha-L-rhamnosidase and beta-D-glucosidase activities. Furthermore, alpha-L
      rhamnosidase and beta-D-glucosidase activities of Veillonella sp. 32 and
      Bacteroides sp. 42 were higher than those of Bacteroides sp. 45 and Bacillus sp.
      52. Based on these results, we can propose the deglycosylated rout of rutin:
      rutin was metabolized to be quercetin-3-O-glucoside by alpha-L-rhamnosidase
      produced from these bacteria, thereafter, quercetin-3-O-glucoside was further
      metabolized by beta-D-glucosidase to form leucocyanidin. Because of the higher
      enzyme activity in Veillonella sp. 32 and Bacteroides sp. 42, quercetin-3-O
      glucoside was completely metabolized to leucocyanidin by these two bacteria. Due
      to the lack of beta-D-glucosidase activity, Bacteroides sp. 22 could not further
      metabolize quercetin-3-O-glucoside to leucocyanidin. This study will be helpful
      for understanding the deglycosylated rout of rutin and the role of different
      intestinal bacteria on the metabolism of natural compounds.

PMID- 22583753
TI  - The molecular biology of memory: cAMP, PKA, CRE, CREB-1, CREB-2, and CPEB.
AB  - The analysis of the contributions to synaptic plasticity and memory of cAMP, PKA,
      CRE, CREB-1, CREB-2, and CPEB has recruited the efforts of many laboratories all
      over the world. These are six key steps in the molecular biological delineation
      of short-term memory and its conversion to long-term memory for both implicit
      (procedural) and explicit (declarative) memory. I here first trace the background
      for the clinical and behavioral studies of implicit memory that made a molecular
      biology of memory storage possible, and then detail the discovery and early
      history of these six molecular steps and their roles in explicit memory.

PMID- 22583757
TI  - Multiple symmetrical lipomatosis: case report and literature review.
AB  - OBJECTIVE: To discuss the pathophysiology and various treatment methods of
      multiple symmetrical lipomatosis. CASE REPORT: We report a case of multiple
      symmetrical lipomatosis in a middle-aged man. He presented to us with an
      extensive, disfiguring neck mass. Clinical examination and computed tomography
      suggested a lipomatous mass without compression of vital neck structures. The
      proximity of the lipomatous mass to the carotid sheaths attracted our interest.
      We performed surgical excision in this case, because of the deep infiltrative
      behaviour of the lipoma. The benefits and drawbacks of liposuction and surgical
      excision of extensive neck lipomatosis are discussed. CONCLUSION: Surgical
      excision and liposuction are complementary treatments in the management of
      multiple symmetrical lipomatosis. Patients should be aware of the limitations of
      both surgical options, and the risk of lipoma recurrence, before surgery. The
      decision on the mode of surgery relies upon the disease extent, the patient's
      expectations and the surgeon's experience.

PMID- 22583756
TI  - Depression assessment by oncologists and palliative care physicians.
AB  - OBJECTIVE: Depression is a frequent problem in cancer patients, which is known to
      reduce quality of life; however, many cancer patients with depression are not
      treated because of the difficulties in assessing depression in this population.
      Our aim was to evaluate and improve the depression assessment strategies of
      palliative care (PC) physicians and oncologists. METHOD: We invited all medical
      oncologists and PC physicians from three cancer centers to participate in this
      multicenter prospective study. They were asked to classify 22 symptoms (related
      and specific to depression in cancer patients, related but not specific, and
      unrelated) as "very important," "important," "less important," or "not important"
      for the diagnosis of depression in cancer patients, at three different time
      points (at baseline, after a video education program, and after 4 weeks). They
      were also asked to complete a questionnaire exploring physicians' perceptions of
      depression and of their role in its systematic screening. RESULTS: All 34
      eligible physicians participated. Baseline performance was good, with >70% of
      participants correctly classifying at least seven of nine related and specific
      symptoms. We found no significant improvement in scores in the immediate and 4
      week follow-up tests. Additionally, 24 (83%) and 23 (79%) participants expressed
      support for systematic depression screening and a role for oncologists in
      screening, respectively. SIGNIFICANCE OF RESULTS: Oncologists had good baseline
      knowledge about depression's main symptoms in cancer patients and a positive
      attitude toward being involved in screening. Underdiagnosis of depression is
      probably related to problems associated with the oncology working environment
      rather than the physicians' knowledge.

PMID- 22583758
TI  - Canine cutaneous leishmaniasis caused by neotropical Leishmania infantum despite
      of systemic disease: A case report.
AB  - Visceral leishmaniasis is an anthropozoonosis caused by a protozoan Leishmania
      infantum (syn. Leishmania chagasi). Here, we report a typical case of canine
      cutaneous leishmaniasis due to L. infantum infection without any other systemic
      symptom in one dog in the city of Rio de Janeiro, Brazil. A mongrel female dog
      was admitted in a veterinary clinic with reports of chronic wounds in the body.
      Physical examination revealed erosive lesions in the limbs, nasal ulcers,
      presence of ectoparasites and seborrheic dermatitis. Blood samples and fragments
      of healthy and injured skin were collected. The complete hemogram revealed
      aregenerative normocytic normochromic anemia and erythrocyte rouleaux, and
      biochemical analysis revealed normal renal and hepatic functions. Cytology of the
      muzzle and skin lesions suggested pyogranulomatous inflammatory process. The
      histopathology of a skin fragment was performed and revealed suspicion of
      protozoa accompanied by necrotizing dermatitis. The diagnosis of leishmaniasis
      was accomplished by positive serology, isolation of Leishmania from the skin
      lesion, and also by molecular test (PCR targeting the conserved region of
      Leishmania kDNA). Culture was positive for damaged skin samples. PCR targeting a
      fragment of Leishmania hsp70 gene was performed employing DNA extracted from
      damaged skin. RFLP of the amplified hsp70 fragment identified the parasite as L.
      infantum, instead of Leishmania braziliensis, the main agent of cutaneous
      leishmaniasis in Rio de Janeiro. Characterization of isolated promastigotes by
      five different enzymatic systems confirmed the species identification of the
      etiological agent. Serology was positive by ELISA and rapid test. This case warns
      to the suspicion of viscerotropic Leishmania in cases of chronic skin lesions and
      brings the discussion of the mechanisms involved in the parasite tissue tropism.

PMID- 22583759
TI  - Proteomic analysis of the pinworm Syphacia muris (Nematoda: Oxyuridae), a
      parasite of laboratory rats.
AB  - Syphacia muris (Nematoda: Oxyuridae) is a ubiquitous nematode that commonly
      infects rats in the laboratory which can interfere in the development of
      biological assays. The somatic extract of S. muris adults collected from infected
      rats was investigated using a proteomic approach. A shot-gun liquid
      chromatography/tandem mass spectrometry procedure was used. We used the MASCOT
      search engine (Matrix-Science) and ProteinPilot software v2.0 (Applied
      Biosystems) for the database search. A total of 359 proteins were accurately
      identified from the worms. The largest protein families consisted of metabolic
      enzymes and those involved in the nucleic metabolism and cell cycle. Proteins of
      transmembrane receptors and those involved in protein metabolism, chaperones,
      structural and motor, signalling and calcium-binding proteins also were
      identified in the proteome of S. muris. Proteome array of S. muris may contribute
      to further elucidation of biological system of S. muris as well as host-parasite
      relationships.

PMID- 22583760
TI  - Comparison of safety and efficacy of bivalirudin versus unfractionated heparin in
      high-risk patients undergoing percutaneous coronary intervention (from the Anti
      Thrombotic Strategy for Reduction of Myocardial Damage During Angioplasty
      Bivalirudin vs Heparin study).
AB  - Bivalirudin, a direct thrombin inhibitor, is as effective as unfractionated
      heparin (UFH), with decreased bleeding in patients with acute coronary syndromes
      who undergo percutaneous coronary intervention (PCI). The aim of this study was
      to evaluate the effectiveness of bivalirudin versus UFH in selected PCI patients
      at high bleeding risk. Four hundred one consecutive patients who underwent PCI
      fulfilling >= 1 enrollment criterion (age >75 years, chronic renal failure, and
      diabetes mellitus) were randomized to bivalirudin (bolus 0.75 mg/kg followed by
      infusion during the procedure; n = 198) or UFH (75 IU/kg; n = 203). In the
      overall population, 39% were aged >75 years, 22% had renal failure, 63% had
      diabetes, and 29% had acute coronary syndromes. The primary efficacy end point
      was the 30-day incidence of major adverse cardiac events (cardiac death,
      myocardial infarction, stent thrombosis, or target vessel revascularization). The
      primary safety end point was the occurrence of any bleeding or entry-site
      complications after PCI. All patients were preloaded with clopidogrel 600 mg.
      Glycoprotein IIb/IIIa inhibitors were used at the operators' discretion. Thirty
      day major adverse cardiac event rates were 11.1% in the bivalirudin group and
      8.9% in the UFH group (p = 0.56); the primary efficacy end point was reached
      mainly because of periprocedural myocardial infarction; 1 patient in the
      bivalirudin group had stent thrombosis. Occurrence of the primary safety end
      point was 1.5% in the bivalirudin group and 9.9% in the UFH group (p = 0.0001);
      this benefit was essentially driven by the prevention of entry-site hematomas >10
      cm (0.5% vs 6.9%, p = 0.002). In conclusion, Anti-Thrombotic Strategy for
      Reduction of Myocardial Damage During Angioplasty-Bivalirudin vs Heparin (ARMYDA
      7 BIVALVE) indicates that bivalirudin, compared with UFH, causes significantly
      lower bleeding and has a similar incidence of major adverse cardiac events in
      patients with older age, diabetes mellitus, or chronic renal failure who undergo
      PCI.

PMID- 22583761
TI  - Assessing capacity for diagnosing tuberculosis in children in sub-Saharan African
      HIV care settings.
AB  - Research on the prevalence of pediatric-specific tuberculosis (TB) diagnostics in
      sub-Saharan Africa is scarce. We assessed the availability of pediatric TB
      diagnostic tests at 651 pediatric human immunodeficiency virus care and treatment
      sites across nine African countries: 54% of  the sites had access to sputum
      culture capacity and 51% to chest X-ray services. While 87% of sites had access
      to smear microscopy, only 6% had the capacity to perform sputum induction and 5%
      to perform gastric aspirate. These findings confirm that diagnostic resources for
      the accurate diagnosis  of pediatric TB are limited. Capacity-building
      initiatives to improve sputum collection in children are urgently required.

PMID- 22583762
TI  - Divergent selection on locally adapted major histocompatibility complex immune
      genes experimentally proven in the field.
AB  - Although crucial for the understanding of adaptive evolution, genetically
      resolved examples of local adaptation are rare. To maximize survival and
      reproduction in their local environment, hosts should resist their local
      parasites and pathogens. The major histocompatibility complex (MHC) with its key
      function in parasite resistance represents an ideal candidate to investigate
      parasite-mediated local adaptation. Using replicated field mesocosms, stocked
      with second-generation lab-bred three-spined stickleback hybrids of a lake and a
      river population, we show local adaptation of MHC genotypes to population
      specific parasites, independently of the genetic background. Increased allele
      divergence of lake MHC genotypes allows lake fish to fight the broad range of
      lake parasites, whereas more specific river genotypes confer selective advantages
      against the less diverse river parasites. Hybrids with local MHC genotype gained
      more body weight and thus higher fitness than those with foreign MHC in either
      habitat, suggesting the evolutionary significance of locally adapted MHC
      genotypes.

PMID- 22583763
TI  - The dynamic expression of Mash1 in the hippocampal subgranular zone after fimbria
      fornix transection.
AB  - Mash1, a member of the basic helix-loop-helix (bHLH) transcription factor family,
      has previously been considered essential for neuronal differentiation and
      specification in the nervous system. In this study, we investigated the
      expression of Mash1 in the hippocampus after fimbria-fornix (FF) transection.
      Western blot showed that protein of Mash1 increased significantly and peaked at
      day 7 after FF transection. Immunofluorescence indicated that after FF
      transection, more newborn cells differentiated into Mash1 positive cells in the
      deafferented side than that in the normal side, and we investigated that in the
      neurogenic area, subgranular zone (SGZ), a part of Mash1 positive cells were NeuN
      positive, and more Mash1/NeuN double positive neurons were identified in the
      deafferented side than that in the normal side. Additionally, the number of
      Mash1/NeuN double positive neurons in SGZ increased significantly and peaked at
      day 7 after FF transection. In vitro, immunofluorescence revealed that extracts
      of the deafferented hippocampus promoted neuronal differentiation to a greater
      extent than extracts from normal hippocampus. Deafferented extracts also enhanced
      Mash1 expression in MAP-2 positive neurons. This study concludes that after FF
      transection, Mash1 expression in the deafferented hippocampus increased and might
      play an important role in inducing local progenitors to differentiate into
      neurons.

PMID- 22583764
TI  - Interactions between vascular endothelial growth factor and neuroglobin.
AB  - Vascular endothelial growth factor (VEGF) and neuroglobin (Ngb) participate in
      neuronal responses to hypoxia and ischemia, but the relationship between their
      effects, if any, is unknown. To address this issue, we measured Ngb levels in
      VEGF-treated mouse cerebrocortical cultures and VEGF levels in cerebrocortical
      cultures from Ngb-overexpressing transgenic mice. VEGF stimulated Ngb expression
      in a VEGFR2/Flk1 receptor-dependent manner, whereas Ngb overexpression suppressed
      expression of VEGF. These findings provide further insight into hypoxia
      stimulated neuronal signaling pathways.

PMID- 22583765
TI  - Inhibition of glutamate and acetylcholine release in behavioral improvement
      induced by electroacupuncture in parkinsonian rats.
AB  - Prior evidence shows that acupuncture improves symptoms in both Parkinson's
      disease (PD) patients and animal models. We examined the effects of high
      frequency (100 Hz) electroacupuncture (EA) on behavior in a rat PD model induced
      by medial forebrain bundle (MFB) transection. Neurotransmitters levels in the
      striatum were measured using in vivo microdialysis and high performance liquid
      chromatography (HPLC). High-frequency EA stimulation at Dazhui (GV14) and Baihui
      (GV20) acupoints decreased rotational behavior induced by apomorphine (APO) and
      improved motor coordination, protected axotomized dopaminergic neurons from
      degeneration in the substantia nigra (SN), it did not increase striatal dopamine
      (DA) levels. However, EA stimulation at acupoints significantly decreased the
      abnormally elevated glutamate (Glu) and acetylcholine (ACh) levels in the
      lesioned side of striatum. Moreover, the Glu levels correlated significantly with
      survival ratios of dopaminergic neurons in the SNc and rotational bahavior. These
      data suggested that behavioral alleviation with EA stimulation may be associated
      with modulation of neurotransmitters release, such as Glu and ACh in the
      striatum, rather than with DA restoration.

PMID- 22583766
TI  - Nylon filament coated with paraffin for intraluminal permanent middle cerebral
      artery occlusion in rats.
AB  - A variety of intraluminal nylon filament has been used in rat middle cerebral
      artery occlusion (MCAO) models. However the lesion extent and its reproducibility
      vary among laboratories. The properties of nylon filament play a part of reasons
      for these variations. In the present study, we used paraffin-coated nylon
      filament for rat MCAO model, tested the effects and advanced improvement for
      making the rat MCAO. Forty male Sprague-Dawley (SD) rats were randomized into two
      groups, MCAO with traditional uncoated nylon filament (uMCAO) and MCAO with
      paraffin-coated nylon filament (cMCAO), three rats as normal group and sham group
      respectively. Assessment included mortality rates, model success rates,
      neurological deficit evaluation, and infarct volume. The study showed two rats
      died in uMCAO group, no rat died in cMCAO group within the 12h. The model success
      rate of uMCAO was 100%, while the uMCAO group was 55% (n=20, two died within 12h,
      seven rats were excluded as the brain slices showed no TTC staining due to
      subarachanoid hemorrhage). Neurological evaluation demonstrated group cMCAO had
      more worse neurological outcomes than group uMCAO, and the difference was
      statistically signification (p<0.05). TTC staining cMCAO group had significantly
      larger infarct volumes than uMCAO group, and also showed statistically
      significant difference (p<0.05). The result demonstrated that the paraffin-coated
      nylon filament intraluminal occlusion provide better occlusion of middle cerebral
      artery than the uncoated nylon filament, improve the consistent of model, and
      raise the success rate to reduce the number of experimental animals. These
      positive results are much encouraging and interesting.

PMID- 22583767
TI  - Acidic preconditioning protects against ischemia-induced brain injury.
AB  - Ischemic preconditioning protects against cerebral ischemia. Recent
      investigations indicated that acidic preconditioning (APC) protects against
      ischemia-induced cardiomyocytes injury. However, it is not clear whether APC can
      protect against cerebral ischemia. To address this issue, C57BL/6 mice were
      exposed 3 times at 10-min intervals to a normoxic atmosphere containing 20% CO(2)
      for 5 min before being further subjected to bilateral common carotid artery
      occlusion. APC reversed the ischemia-induced brain injury as revealed by improved
      performance in passive avoidance experiments and decreased neuron loss in the
      hippocampal CA1 region. Consistently, both APC-treated brain slices and primary
      cultured neurons were more resistant to oxygen-glucose-deprivation (OGD)-induced
      injury, in a pH- and time-dependent manner, as revealed by reversed cell/tissue
      viability. In addition, the APC treatment prevented OGD-induced mitochondrial
      transmembrane potential loss and apoptosis, which was inhibited by the
      mitochondrial permeability transport pore opener atractyloside. Taken together,
      these findings indicated that APC protects against ischemia-induced neuronal
      injury. The beneficial effects may be attributed, at least in part, to decreased
      mitochondria-dependent neuronal apoptosis.

PMID- 22583768
TI  - CRMP4 mediates MAG-induced inhibition of axonal outgrowth and protection against
      Vincristine-induced axonal degeneration.
AB  - Suppression of inhibition of axonal outgrowth and promotion of axonal protection
      from progressive axonal degeneration are both therapeutic strategies for the
      treatment of neuronal diseases characterized by axonal loss. Myelin-associated
      inhibitors (MAIs) have been shown to suppress axonal outgrowth, but a specific
      MAI, myelin-associated glycoprotein (MAG), has also been shown to protect neurons
      from axonal degeneration through activation of the small GTPase protein RhoA.
      Recent in vitro studies have shown that collapsin response mediator protein 4
      (CRMP4) interacts with RhoA and that the CRMP4b/RhoA complex mediates MAG-induced
      inhibitory signaling against axonal outgrowth. However, whether CRMP4 is involved
      in MAG-mediated axon protection signaling remains unclear. Here, we show
      involvement of CRMP4 in MAG-induced inhibition of axonal outgrowth and axonal
      protection using the CRMP4-/- mouse model. In dorsal root ganglion (DRG) neurons,
      loss of CRMP4 prevents MAG-induced inhibition of axonal outgrowth and growth cone
      collapse and increases sensitivity to microtubule destabilizing factor
      Vincristine (VNC)-induced axonal degeneration. MAG-mediated axon protection
      against VNC is suppressed in CRMP4-/- DRG neurons. Understanding the molecular
      mechanism of MAG-mediated inhibition and protection via CRMP4 may provide novel
      opportunities to control axonal degeneration and regeneration.

PMID- 22583770
TI  - The slow-scale linear noise approximation: an accurate, reduced stochastic
      description of biochemical networks under timescale separation conditions.
AB  - BACKGROUND: It is well known that the deterministic dynamics of biochemical
      reaction networks can be more easily studied if timescale separation conditions
      are invoked (the quasi-steady-state assumption). In this case the deterministic
      dynamics of a large network of elementary reactions are well described by the
      dynamics of a smaller network of effective reactions. Each of the latter
      represents a group of elementary reactions in the large network and has
      associated with it an effective macroscopic rate law. A popular method to achieve
      model reduction in the presence of intrinsic noise consists of using the
      effective macroscopic rate laws to heuristically deduce effective probabilities
      for the effective reactions which then enables simulation via the stochastic
      simulation algorithm (SSA). The validity of this heuristic SSA method is a priori
      doubtful because the reaction probabilities for the SSA have only been rigorously
      derived from microscopic physics arguments for elementary reactions. RESULTS: We
      here obtain, by rigorous means and in closed-form, a reduced linear Langevin
      equation description of the stochastic dynamics of monostable biochemical
      networks in conditions characterized by small intrinsic noise and timescale
      separation. The slow-scale linear noise approximation (ssLNA), as the new method
      is called, is used to calculate the intrinsic noise statistics of enzyme and gene
      networks. The results agree very well with SSA simulations of the non-reduced
      network of elementary reactions. In contrast the conventional heuristic SSA is
      shown to overestimate the size of noise for Michaelis-Menten kinetics,
      considerably under-estimate the size of noise for Hill-type kinetics and in some
      cases even miss the prediction of noise-induced oscillations. CONCLUSIONS: A new
      general method, the ssLNA, is derived and shown to correctly describe the
      statistics of intrinsic noise about the macroscopic concentrations under
      timescale separation conditions. The ssLNA provides a simple and accurate means
      of performing stochastic model reduction and hence it is expected to be of
      widespread utility in studying the dynamics of large noisy reaction networks, as
      is common in computational and systems biology.

PMID- 22583769
TI  - Transcription profiling reveals stage- and function-dependent expression patterns
      in the filarial nematode Brugia malayi.
AB  - BACKGROUND: Brugia malayi is a nematode parasite that causes lymphatic
      filariasis, a disfiguring and disabiling tropical disease. Although a first draft
      genome sequence was released in 2007, very little is understood about
      transcription programs that govern developmental changes required for the
      parasite's development and survival in its mammalian and insect hosts. RESULTS:
      We used a microarray with probes that represent some 85% of predicted genes to
      generate gene expression profiles for seven parasite life cycle stages/sexes.
      Approximately 41% of transcripts with detectable expression signals were
      differentially expressed across lifecycle stages. Twenty-six percent of
      transcripts were exclusively expressed in a single parasite stage, and 27% were
      expressed in all stages studied. K-means clustering of differentially expressed
      transcripts revealed five major transcription patterns that were associated with
      parasite lifecycle stages or gender. Examination of known stage-associated
      transcripts validated these data sets and suggested that newly identified stage
      or gender-associated transcripts may exercise biological functions in development
      and reproduction. The results also indicate that genes with similar transcription
      patterns were often involved in similar functions or cellular processes. For
      example, nuclear receptor family gene transcripts were upregulated in gene
      expression pattern four (female-enriched) while protein kinase gene family
      transcripts were upregulated in expression pattern five (male-enriched). We also
      used pair-wise comparisons to identify transcriptional changes between life cycle
      stages and sexes. CONCLUSIONS: Analysis of gene expression patterns of lifecycle
      in B. malayi has provided novel insights into the biology of filarial parasites.
      Proteins encoded by stage-associated and/or stage-specific transcripts are likely
      to be critically important for key parasite functions such as establishment and
      maintenance of infection, development, reproduction, and survival in the host.
      Some of these may be useful targets for vaccines or new drug treatments for
      filariasis.

PMID- 22583771
TI  - Aldehyde dehydrogenase 1 is associated with recurrence-free survival but not stem
      cell-like properties in hepatocellular carcinoma.
AB  - AIM:   It has been reported that aldehyde dehydrogenase 1 A1 (ALDH1) could be not
      only a normal stem cell marker but also a cancer stem cell marker. ALDH1
      expression could be a predictor of poor prognosis in a wide range of cancers.
      However, the role of ALDH1 in hepatocellular carcinoma (HCC) remains unclear.
      METHOD:   We conducted loss-of-function assays for ALDH1 by using short-hairpin
      RNA in HCC cells and evaluated the correlation between ALDH1 expression and
      clinicopathological features based on immunohistochemical assessment of 49
      primary HCC tissues. RESULTS:   Neither cell proliferation nor the anchorage
      independent sphere formation ability of HCC cells were altered after ALDH1
      knockdown. Flow cytometric analyses revealed that ALDH1 knockdown showed no
      remarkable change in the proportion of epithelial cell adhesion molecule
      (EpCAM)(+)  tumor-initiating cells. Although non-tumor tissues in primary HCC
      samples diffusely and homogenously expressed ALDH1 at low levels, tumor tissues
      contained cells with high levels of ALDH1 expression at varying frequencies.
      Primary HCC samples were categorized as ALDH1-high or ALDH1-low based on the
      percentage of ALDH1-overexpressing cells. ALDH1-high HCC was characterized by low
      serum levels of alpha-fetoprotein (P < 0.01) and well-differentiated pathology (P
      = 0.03). Multivariate analysis showed that high ALDH1 expression was a favorable
      prognostic factor in recurrence-free survival of HCC (P = 0.02). CONCLUSION:  
      Our findings show that ALDH1 expression has little association with stem cell
      like features in HCC cells. ALDH1 might function as a differentiation marker
      rather than a stem cell marker in HCC.

PMID- 22583772
TI  - Different interface orientations of pentacene and PTCDA induce different degrees
      of disorder.
AB  - : Organic polymers or crystals are commonly used in manufacturing of today's
      electronically functional devices (OLEDs, organic solar cells, etc).
      Understanding their morphology in general and at the interface in particular is
      of paramount importance. Proper knowledge of molecular orientation at interfaces
      is essential for predicting optoelectronic properties such as exciton diffusion
      length, charge carrier mobility, and molecular quadrupole moments. Two promising
      candidates are pentacene and 3,4:9,10-perylenetetracarboxylic dianhydride
      (PTCDA). Different orientations of pentacene on PTCDA have been investigated
      using an atomistic molecular dynamics approach. Here, we show that the degree of
      disorder at the interface depends largely on the crystal orientation and that
      more ordered interfaces generally suffer from large vacancy formation.

PMID- 22583773
TI  - The effectiveness of adhering to clinical-practice guidelines for anxiety
      disorders in secondary mental health care: the results of a cohort study in the
      Netherlands.
AB  - BACKGROUND: While studies into the implementation of clinical practice guidelines
      for mental health care are scarce, studies on the effectiveness of implementing
      practice guidelines for anxiety disorders appear to be entirely non-existent.
      OBJECTIVE: To examine whether adherence to anxiety disorder clinical practice
      guidelines in secondary mental health care yields superior treatment results than
      non-adherence. METHOD: A closed-cohort study of 181 outpatients with an anxiety
      disorder or hypochondriasis who were treated in a routine mental health setting.
      Preceding the inclusion of these 181 patients, a start was made on the
      implementation of the Dutch national multidisciplinary practice guidelines for
      anxiety disorders. Patients were asked to complete several questionnaires before
      the start of treatment and again 1 year later. The medical records of these
      patients were reviewed to assess guideline adherence. Ultimately, adherence or
      non-adherence to the different treatment algorithms described in the guidelines
      was related to changes in the severity of psychiatric symptomatology, psychiatric
      functioning, general well-being and satisfaction with treatment. RESULTS:
      Compared with patients whose treatment did not adhere to the guidelines, those
      whose treatment adhered to the guidelines were found to have greater symptom
      reduction after 1 year (P < 0.01). The latter group of patients also rated their
      satisfaction with their treatment significantly higher (P = 0.01). No significant
      differences were found after 1 year with respect to changes in impairment of
      functioning and quality of life in the two groups of patients. CONCLUSIONS:
      Adherence to anxiety disorder guidelines yields superior treatment results and
      increased patient satisfaction with treatment when compared with patients whose
      treatment did not adhere to the clinical guidelines. These results should
      encourage a more widespread implementation of such guidelines in mental health
      care facilities.

PMID- 22583774
TI  - Severe post-renal acute kidney injury, post-obstructive diuresis and renal
      recovery.
AB  - Study Type--Therapy (case series) Level of Evidence 4. What's known on the
      subject? and What does the study add? The pathophysiology of post-renal acute
      kidney injury (PR-AKI), i.e. caused by urinary tract obstruction, has been
      extensively studied in animal models but clinical studies on this subject are
      outdated, and/or have focused on the mechanisms of 'post-obstructive diuresis'
      (POD), a potentially life-threatening polyuria that can develop after the release
      of obstruction. In severe PR-AKI, the risk of occurrence of POD is high. POD
      occurrence predicts renal recovery without the persistence of severe chronic
      kidney failure. In the present study, the occurrence of POD and the persistence
      of chronic renal sequelae could be predicted early from clinical variables at
      admission before the release of obstruction. OBJECTIVE: * To identify predictors
      of post-obstructive diuresis (POD) occurrence or severe chronic renal failure
      (CRF) persistence after the release of urinary tract obstruction in the setting
      of post-renal acute kidney injury (PR-AKI). PATIENTS AND METHODS: * Bi-centre
      retrospective observational study of all patients with PR-AKI treated in two
      intensive care units (ICUs) from 1998 to 2010. * Clinical, biological and imaging
      characteristics on admission and after the release of obstruction were analysed
      with univariate and, if possible, multivariate analysis to search for predictors
      of (i) occurrence of POD (diuresis >4 L/day) after the release of obstruction;
      (ii) persistence of severe CRF (estimated glomerular filtration rate <30
      mL/min/1.73 m(2), including end-stage CRF) at 3 months. RESULTS: * On admission,
      median (range) serum creatinine was 866 (247-3119) umol/L. * POD occurred in 34
      (63%) of the 54 analysable patients. On admission, higher serum creatinine (Odds
      ratio [OR] 1.002 per 1 umol/L, 95% confidence interval [CI] 1.000-1.004, P =
      0.004), higher serum bicarbonate (OR 1.36 per 1 mmol/L, 95% CI 1.13-1.65, P <
      0.001), and urinary retention (OR 6.96, 95% CI 1.34-36.23, P = 0.01)
      independently predicted POD occurrence. * Severe CRF persisted in seven (21%) of
      the 34 analysable patients, including two (6%) cases of end-stage CRF. Predictors
      of severe CRF persistence after univariate analysis were: lower blood haemoglobin
      (P < 0.001) and lower serum bicarbonate (P = 0.03) on admission, longer time from
      admission to the release of obstruction (P = 0.01) and absence of POD (P = 0.04)
      after the release of obstruction. CONCLUSIONS: * In severe PR-AKI treated in ICU,
      POD occurrence was a frequent event that predicted renal recovery without severe
      CRF. * POD occurrence or severe CRF persistence could be predicted early from
      clinical and biological variables at admission before the release of obstruction.

PMID- 22583775
TI  - A measure for quantifying the impact of housing quality on respiratory health: a
      cross-sectional study.
AB  - BACKGROUND: Damp and mould in homes have been established as risk factors for
      respiratory health. There is a need for a relatively straightforward assessment
      of the home that quantifies this risk. METHODS: Using data from 891 New Zealand
      houses, the utility of a Respiratory Hazard Index quantifying key attributes
      related to damp and mould was tested by studying its associations with self
      reported respiratory symptoms. RESULTS: A dose-response relationship was found
      whereby each unit increase in the Respiratory Hazard Index was associated with an
      11% increase in the odds of at least one episode of wheezing/whistling in the
      chest over the last 12 months (relative odds of 1.11 with a 95% CI 1.04%-1.20%).
      An 11% increase in the odds of an asthma attack over the last 12 months was
      estimated (relative odds of 1.11 with a 95% CI 1.01%-1.22%). These estimates were
      adjusted for household crowding levels, age, sex and smoking status. There was
      suggestive evidence of more steeply increasing odds of respiratory symptoms with
      increasing levels of the Respiratory Hazard Index for children aged under 7. In
      the worst performing houses according to the Index, a 33% reduction in the number
      of people experiencing respiratory symptoms (relative risk 0.67 with 95% CI 0.53
      to 0.85) could be expected if people were housed in the best performing houses.
      CONCLUSIONS: This study showed that increased evidence of housing conditions
      supporting dampness and mould was associated with increased odds of respiratory
      symptoms. A valid housing assessment tool can provide a rational basis for
      investment in improved housing quality to improve respiratory health.

PMID- 22583776
TI  - Infected bronchogenic cyst causing dysphagia and retrosternal pain.
AB  - Bronchogenic cysts are congenital. They are typically discovered in infancy or
      early childhood. Secondary infection of the cyst is uncommon. We present the case
      of a 17-year-old female who presented to the emergency department with
      intermediate onset of upper abdominal, and retrosternal chest pain and fever.
      Subsequent X-ray and computerised tomography scan showed a bronchogenic cyst. The
      patient underwent subacute thoracotomy where a bronchogenic cyst filled with pus
      was located and excised. Bronchogenic cysts can be a rare cause of retrosternal
      pain.

PMID- 22583778
TI  - Anticancer and radiosensitizing evaluation of some new pyranothiazole-Schiff
      bases bearing the biologically active sulfonamide moiety.
AB  - The present work reports the synthesis of some new Schiff bases, 5-(substituted
      benzylideneamino)-6-cyano-7H-7-(4-methoxyphenyl)-2-(4-sulphamoylphenylamino)
      pyrano[2,3-d]thiazole (5-15). The design of the structures of these compounds
      complies with the general pharmacophoric requirements for CA inhibiting
      anticancer drugs. The newly synthesized compounds were evaluated for their in
      vitro anticancer activity against human breast cancer cell line (MCF7). Most of
      the screened compounds showed interesting cytotoxic activities compared to
      doxorubicin as a reference drug. Compounds 4, 6-8 and 11 (IC(50): 27.51, 10.25,
      9.55, 9.39 and 9.70 MUM, respectively) exhibited higher cytotoxic activities than
      the reference drug doxorubicin (IC(50): 32.00 MUM). Additionally, the previously
      mentioned compounds were evaluated again for their ability to enhance the cell
      killing effect of gamma-radiation.

PMID- 22583777
TI  - Co-administration phenoxodiol with doxorubicin synergistically inhibit the
      activity of sphingosine kinase-1 (SphK1), a potential oncogene of osteosarcoma,
      to suppress osteosarcoma cell growth both in vivo and in vitro.
AB  - Elucidation of the mechanisms of chemo-resistance and implementation of
      strategies to overcome it will be pivotal to improve the survival for
      osteosarcoma (OS) patients. We here suggest that sphingosine kinase-1 (SphK1)
      might be the key factor contributing to chemo-resistance in OS. Our Western-blots
      and immunohistochemistry results showed that SphK1 is over-expressed in multiple
      clinical OS tissues. Over-expression of SphK1 in OS cell line U2OS promoted its
      growth and endorsed its resistance against doxorubicin, while knocking-down of
      SphK1 by shRNA inhibited U2OS cell growth and increased its sensitivity to
      doxorubicin. Co-administration phenoxodiol with doxorubicin synergistically
      inhibited SphK1 activity to trigger cellular ceramide accumulation, and achieved
      synergistic anti-OS growth effect, accompanied with a significant increased of
      apoptosis and cytotoxicity. Increased cellular level of ceramide by the co
      administration induced the association between Akt and Protein Phosphatase 1
      (PP1) to dephosphorylate Akt, and to introduce a constitutively active Akt (CA
      Akt) restored Akt activation and diminished cell growth inhibition. Further,
      phenoxodiol and doxorubicin synergistically activated apoptosis signal-regulating
      kinase 1(ASK1)/c-jun-NH2-kinase (JNK) signaling, which also contributed to cell
      growth inhibition. Significantly, the role of SphK1 in OS cell growth and the
      synergistic anti-OS effect of phenoxodiol and doxorubicin were also seen in a
      mice OS xenograft model. In conclusion, our data suggest that SphK1 might be a
      critical oncogene of OS and co-administration phenoxodiol with doxorubicin
      synergistically inhibited the activity of SphK1 to suppress osteosarcoma cell
      growth both in vivo and in vitro.

PMID- 22583779
TI  - Synthesis, in vitro and in silico screening of ethyl 2-(6-substituted
      benzo[d]thiazol-2-ylamino)-2-oxoacetates as protein-tyrosine phosphatase 1B
      inhibitors.
AB  - The ethyl 2-(6-substituted benzo[d]thiazol-2-ylamino)-2-oxoacetate derivatives
      (OX 1-9) were prepared using a one-step reaction. The in vitro inhibitory
      activity of the compounds against protein tyrosine phosphatase 1B (PTP-1B) was
      evaluated. Compounds OX-(1, 6 and 7) were rapid reversible (mixed-type)
      inhibitors of PTP-1B with IC(50) values in the low micro-molar range. The most
      active compounds OX-(1, 6 and 7) were docked into the crystal structure of PTP
      1B. Docking results indicate potential hydrogen bond interactions between the
      oxamate group in all compounds and the catalytic amino acid residues Arg221 and
      Ser216. The compounds were evaluated for their in vivo hypoglycemic activity,
      showing significant lowering of plasma glucose concentration in acute
      normoglycemic model and oral glucose tolerance test similarly at the effect
      exerted for hypoglycemic drug glibenclamide.

PMID- 22583780
TI  - Routinization and medicalization of palliative care: losses, gains and
      challenges.
AB  - This article investigates some of the criticisms that have been directed at the
      hospice movement in the process of interaction with the traditional Western
      healthcare system, such as those relative to its routinization and
      medicalization. It also aims to review some of the consequences of this process
      of institutionalisation for the field of end-of-life care: surveillance and
      control over the process of dying, at the expense of decisions preferably based
      on the patient and that patient's ability to decide how to die, with the loss of
      wider objectives originally established by the movement, such as unconditional
      reception for the patient. Based on these criticisms, some considerations are
      made regarding the moral implications and risks related to this specific mode of
      action, the hospice way of care. 

PMID- 22583781
TI  - Case of bilateral pneumolabyrinth presenting as sudden, bilateral deafness,
      without temporal bone fracture, after a fall.
AB  - OBJECTIVE: We report a case of bilateral pneumolabyrinth presenting as sudden,
      bilateral deafness, without temporal bone fracture, after a fall. CASE REPORT: A
      49-year-old man presented with sudden, bilateral deafness and whirling vertigo,
      without any other neurological manifestations. Temporal bone computed tomography
      clearly demonstrated the presence of air in the vestibule and cochlea on both
      sides. However, there was no definite fracture line, ossicular chain anomaly or
      soft tissue density in the temporal bone or middle-ear cavity. The patient was
      treated conservatively. Unfortunately, there was no improvement in his hearing.
      CONCLUSION: Pneumolabyrinth is an uncommon condition in which air is present in
      the vestibule or cochlea. It is rarely found, even with fractures violating the
      otic capsule or with transverse fractures of the temporal bone. In addition, its
      bilateral occurrence is extremely rare. In this article, we describe a case of
      bilateral pneumolabyrinth presenting as sudden, bilateral deafness, without
      temporal bone fracture, an occurrence which has not previously been reported.

PMID- 22583782
TI  - Antibiotic strategy in severe community-acquired pneumococcal pneumonia.
AB  - OBJECTIVE: The authors had for aim to make an inventory of antibiotic treatment
      for severe community-acquired Streptococcus pneumoniae pneumonia and compare
      local practices to the local and national guidelines. PATIENTS AND METHOD: An
      audit was conducted retrospectively in the Versailles hospital ICU between
      January 2006 and April 2009. Forty patients were included. RESULTS: Ninety-three
      percent had major risk factors for pneumonia. Ninety-eight percent were treated,
      with the usual empirical treatment (69%) or treatment active against Pseudomonas
      aeruginosa (31%). Eighty-five percent of empirical treatment complied with the
      French national guidelines issued by the SPILF and 49% with the local ICU
      protocol, more restrictive for the choice of the agent and dose. Early de
      escalation to amoxicillin was applied to 41% of patients after obtaining results
      for pneumococcal and Legionella antigen and results of respiratory sample direct
      examination. For all patients, empirical treatment was reassessed according to
      culture results: 81% were prescribed amoxicillin. Evaluation showed that 92% of
      treatment complied with SPILF guidelines and 65% with the local ICU protocol that
      required adaptation of amoxicillin doses according to MICs; adaptation to
      severity and BMI was necessary for ten patients. Mortality remained high, at 37%,
      despite using antibiotics still effective against S. pneumoniae. CONCLUSIONS:
      This survey revealed a satisfactory adhesion to recommendations and prompt
      responsiveness of the team for adjustment of antibiotic therapy. The audit
      allowed updating the local ICU protocol.

PMID- 22583783
TI  - Environmental impact of flood: the study of arsenic speciation in exchangeable
      fraction of flood deposits of Warta river (Poland) in determination of "finger
      prints" of the pollutants origin and the ways of the migration.
AB  - The paper presents the application of the hyphenated technique - high-performance
      liquid chromatography with atomic absorption spectrometry detection with hydride
      generation (HPLC-HG-AAS) - in the determinations of inorganic forms of arsenic:
      As(III) and As(V) in the exchangeable fraction of flood deposits. The separation
      of analytical signals of the determined arsenic forms was obtained using an ion
      exchange column in a chromatographic system with the atomic absorption
      spectrometer as a detector, at the determination limits of 5 ngg(-1) for As(III)
      and 10 ngg(-1) for As(V). Flood deposits were collected after big flood event in
      valley of the Warta river which took place in summer 2010. Samples of overbank
      deposits were taken in Poznan agglomeration and vicinity (NW Poland). The results
      of determinations of arsenic forms in the exchangeable fraction of flood deposits
      allowed indication of a hypothetical path of deposits migration transported by a
      river during flood and environmental threats posed by their deposition by flood.

PMID- 22583784
TI  - Effectiveness of urease inhibition on the abatement of ammonia, nitrous oxide and
      nitric oxide emissions in a non-irrigated Mediterranean barley field.
AB  - Urea is considered the cheapest and most commonly used form of inorganic N
      fertilizer worldwide. However, its use is associated with emissions of ammonia
      (NH(3)), nitrous oxide (N(2)O) and nitric oxide (NO), which have both economic
      and environmental impact. Urease activity inhibitors have been proposed as a
      means to reduce NH(3) emissions, although limited information exists about their
      effect on N(2)O and NO emissions. In this context, a field experiment was carried
      out with a barley crop (Hordeum vulgare L.) under Mediterranean conditions to
      test the effectiveness of the urease inhibitor N-(n-butyl) thiophosphoric
      triamide (NBPT) on reducing these gaseous N losses from surface applied urea.
      Crop yield, soil mineral N concentrations, dissolved organic carbon (DOC),
      denitrification potential, NH(3), N(2)O and NO fluxes were measured during the
      growing season. The inclusion of the inhibitor reduced NH(3) emissions in the 30
      d following urea application by 58% and net N(2)O and NO emissions in the 95 d
      following urea application by 86% and 88%, respectively. NBPT addition also
      increased grain yield by 5% and N uptake by 6%, although neither increase was
      statistically significant. Under the experimental conditions presented here,
      these results demonstrate the potential of the urease inhibitor NBPT in abating
      NH(3), N(2)O and NO emissions from arable soils fertilized with urea, slowing
      urea hydrolysis and releasing lower concentrations of NH(4)(+) to the upper soil
      layer.

PMID- 22583785
TI  - Influence of Suwannee River humic acid on particle properties and toxicity of
      silver nanoparticles.
AB  - Adsorption of natural organic matter (NOM) on nanoparticles can have dramatic
      impacts on particle dispersion resulting in altered fate and transport as well as
      bioavailability and toxicity. In this study, the adsorption of Suwannee River
      humic acid (SRHA) on silver nanoparticles (nano-Ag) was determined and showed a
      Langmuir adsorption at pH 7 with an adsorption maximum of 28.6 mg g(-1) nano-Ag.
      It was also revealed that addition of <10 mg L(-1) total organic carbon (TOC)
      increased the total Ag content suspended in the aquatic system, likely due to
      increased dispersion. Total silver content decreased with concentrations of NOM
      greater than 10mg TOCL(-1) indicating an increase in nanoparticle agglomeration
      and settling above this concentration. However, SRHA did not have any significant
      effect on the equilibrium concentration of ionic Ag dissolved in solution.
      Exposure of Daphnia to nano-Ag particles (50 MUg L(-1) and pH 7) produced a
      linear decrease in toxicity with increasing NOM. These results clearly indicate
      the importance of water chemistry on the fate and toxicity of nanoparticulates.

PMID- 22583786
TI  - Metal removal from oil sands tailings pond water by indigenous micro-alga.
AB  - This paper reports the removal of ten target metals of environmental concern
      ((53)Cr, Mn, Co, (60)Ni, (65)Cu, (66)Zn, As, (88)Sr, (95)Mo, and Ba) from oil
      sands tailings pond water. The organism responsible for removal was found to be
      an indigenous green micro-alga identified as Parachlorella kessleri by sequencing
      of the 23S rRNA gene. P. kessleri grew in tailings pond water samples taken from
      two oil sands operators (Syncrude Canada Ltd. and Albian Sands Energy Inc.), and
      enriched with low (0.24 mM NO(3)(-) and 0.016 mM PO(4)(-3)) and high (1.98 mM
      NO(3)(-) and 0.20mM PO(4)(-3)) concentrations of nutrient supplements (the most
      realistic scenario). The removal of (60)Ni, (65)Cu, As, (88)Sr, (95)Mo, and Ba
      from Syncrude tailings pond water was significantly enhanced by high
      concentrations of nitrogen and phosphorus, whereas the high nutrient
      concentrations adversely affected the removal of Co, (60)Ni, As, (88)Sr, and Mo
      in samples of Albian tailings pond water. Based on ANOVA two-factor analysis,
      higher nutrient concentration does not always result in higher metal removal, and
      TPW source must also be considered.

PMID- 22583787
TI  - Biomarker responses as indication of contaminant effects in Oreochromis
      niloticus.
AB  - The current study investigated oxidative stress parameters (enzymes activities,
      metallothionein content and lipid peroxidation) in freshwater fish, Oreochromis
      niloticus, tilapia exposure to Monjolinho River (in 4 months of year: January,
      April, July and November). One critical site in Monjolinho River (site B) was
      assessed in comparison to a reference site (site A). Water pH and oxygen
      concentration was lower than that recommended by CONAMA (Brazilian National
      Environmental Committee), resolution 357/2005 for protection of aquatic
      communities, and ammonium and the metals Cu, Zn, Mn and Fe (on all months)
      concentrations were higher than the maximum concentration recommended.
      Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were
      significantly decreased in liver and muscle in tilapia from Monjolinho River,
      throughout the year, in relation to reference except in gills that SOD activity
      increased. Glutathione S-transferase (GST) activity was significantly increased
      in liver of the tilapia from Monjolinho River in all sites, in relation to
      reference except in gills that GST activity increased in July and decreased in
      November, suggesting that GST activity could be induced to neutralize the
      pollutants toxicity. On the other hand, GST activity was significantly decreased
      in white muscle indicating a toxic effect of pollutants, resulting in a decreased
      ability of tilapia to perform defense reactions associated to GSTs. The decrease
      of catalase (CAT) activity in gills of the O. niloticus together with the
      increase of SOD activity, could explain the increased lipid peroxidation (LPO)
      level in this organ. Metallothionein levels in liver and gills were significantly
      high in all sites. Results indicate that the exposure to metals caused severe
      damage to tissues; despite the consensually assumed antioxidant induction as a
      sign of exposure to contaminants the effects seem in part to be mediated by
      suppression of antioxidant system with SOD, CAT and GPx as potential candidates
      for tissues toxicity biomarkers of pollutants.

PMID- 22583788
TI  - Caspases in synaptic plasticity.
AB  - Caspases are a family of cysteine proteases that play key roles in programmed
      cell death (apoptosis). Mounting evidence in recent years shows that caspases
      also have important non-apoptotic functions in multiple cellular processes, such
      as synaptic plasticity, dendritic development, learning and memory. In this
      article, we review the studies on the non-apoptotic functions of caspases in
      neurons, with a focus on their roles in synaptic plasticity, learning and memory
      and neurodegeneration.

PMID- 22583790
TI  - Differential cell adhesion on mesoporous silicon substrates.
AB  - Porous silicon (PSi) is a promising material in several biomedical applications
      because of its biocompatibility and biodegradability. Despite the plethora of
      studies focusing on the interaction of cells with micrometer and submicro
      geometrical features, limited information is available on the response of cells
      to substrates with a quasi-regular distribution of nanoscopic pores. Here, the
      behavior of four different cell types is analyzed on two mesoporous (MeP) silicon
      substrates, with an average pore size of ~5 (MeP1) and ~20 nm (MeP2),
      respectively. On both MeP substrates, cells are observed to spread and adhere in
      a larger number as compared to flat silicon wafers. At all considered time
      points, the surface density of the adhering cells nd is larger on the PSi
      substrate with the smaller average pore size (MeP1). At 60 h, nd is from ~1.5 to
      5 times larger on MeP1 than on MeP2 substrates, depending on the cell type. The
      higher rates of proliferation are observed for the two neuronal cell types, the
      mouse neuroblastoma cells (N2A) and the immortalized human cortical neuronal
      cells (HCN1A). It is speculated that the higher adhesion on MeP1 could be
      attributed to a preferential matching of the substrate topography with the
      recently observed multiscale molecular architecture of focal adhesions. These
      results have implications in the rational development of PSi substrates for
      supporting cell adhesion and controlling drug release in implants and scaffolds
      for tissue engineering applications. 

PMID- 22583791
TI  - The morphology and evolution of the female postabdomen of Holometabola (Insecta).
AB  - In the present article homology issues, character evolution and phylogenetic
      implications related to the female postabdomen of the holometabolan insects are
      discussed, based on an earlier analysis of a comprehensive morphological data
      set. Hymenoptera, the sistergroup of the remaining Holometabola, are the only
      group where the females have retained a fully developed primary ovipositor of the
      lepismatid type. There are no characters of the female abdomen supporting a clade
      Coleopterida + Neuropterida. The invagination of the terminal segments is an
      autapomorphy of Coleoptera. The ovipositor is substantially modified in
      Raphidioptera and distinctly reduced in Megaloptera and Neuroptera. The entire
      female abdomen is extremely simplified in Strepsiptera. The postabdomen is
      tapering posteriorly in Mecopterida and retractile in a telescopic manner
      (oviscapt). The paired ventral sclerites of segments VIII and IX are preserved,
      but valvifers and valvulae are not distinguishable. In Amphiesmenoptera
      sclerotizations derived from the ventral appendages VIII are fused
      ventromedially, forming a solid plate, and the appendages IX are reduced. The
      terminal segments are fused and form a terminal unit which bears the genital
      opening subapically. The presence of two pairs of apophyses and the related
      protraction of the terminal unit by muscle force are additional autapomorphies,
      as is the fusion of the rectum with the posterior part of the genital chamber
      (cloaca). Antliophora are supported by the presence of a transverse muscle
      between the ventral sclerites of segment VIII. Secondary egg laying tubes have
      evolved independently within Boreidae (absent in Caurinus) and in Tipulomorpha.
      The loss of two muscle associated with the genital chamber are likely
      autapomorphies of Diptera. The secondary loss of the telescopic retractability of
      the postabdomen is one of many autapomorphies of Siphonaptera.

PMID- 22583789
TI  - Is the process of delivery of an individually tailored lifestyle intervention
      associated with improvements in LDL cholesterol and multiple lifestyle behaviours
      in people with familial hypercholesterolemia?
AB  - BACKGROUND: More insight in the association between reach, dose and fidelity of
      intervention components and effects is needed. In the current study, we aimed to
      evaluate reach, dose and fidelity of an individually tailored lifestyle
      intervention in people with Familial Hypercholesterolemia (FH) and the
      association between intervention dose and changes in LDL-Cholesterol (LDL-C), and
      multiple lifestyle behaviours at 12-months follow-up. METHODS: Participants (n =
      181) randomly allocated to the intervention group received the PRO-FIT
      intervention consisting of computer-tailored lifestyle advice (PRO-FIT*advice)
      and counselling (face-to-face and telephone booster calls) using Motivational
      Interviewing (MI). According to a process evaluation plan, intervention reach,
      dose delivered and received, and MI fidelity were assessed using the recruitment
      database, website/counselling logs and the Motivational Interviewing Treatment
      Integrity (MITI 3.1.1.) code. Regression analyses were conducted to explore
      differences between participant and non-participant characteristics, and the
      association between intervention dose and change in LDL-C, and multiple lifestyle
      behaviours. RESULTS: A 34% (n = 181) representative proportion of the intended
      intervention group was reached during the recruitment phase; participants did not
      differ from non-participants (n = 623) on age, gender and LDL-C levels. Of the
      participants, 95% received a PRO-FIT*advice log on account, of which 49% actually
      logged on and completed at least one advice module. Nearly all participants
      received a face-to-face counselling session and on average, 4.2 telephone booster
      calls were delivered. None of the face-to-face sessions were implemented
      according to MI guidelines. Overall, weak non-significant positive associations
      were found between intervention dose and LDL-C and lifestyle behaviours.
      CONCLUSIONS: Implementation of the PRO-FIT intervention in practice appears
      feasible, particularly PRO-FIT*advice, since it can be relative easily
      implemented with a high dose delivered. However, only less than half of the
      intervention group received the complete intervention-package as intended.
      Strategies to let participants optimally engage in using web-based computer
      tailored interventions like PRO-FIT*advice are needed. Further, more emphasis
      should be put on more extensive MI training and monitoring/supervision.

PMID- 22583792
TI  - The thoracic skeleto-muscular system of Mengenilla (Strepsiptera: Mengenillidae)
      and its phylogenetic implications.
AB  - The thorax of Mengenilla was examined using traditional morphological techniques
      and its features were documented in detail using scanning electron microscopy and
      computer-based 3D reconstructions. The results were compared to conditions found
      in other holometabolan insects. The implications for the systematic placement of
      Strepsiptera are discussed. The observations are interpreted in the light of the
      recently confirmed sistergroup relationship between Strepsiptera and Coleoptera
      (Coleopterida). The synapomorphies of the thorax of Strepsiptera and Coleoptera
      are partly related with posteromotorism (e.g., increased size of the metathorax),
      partly with a decreased intrathoracic flexibility (e.g., a fused pronotum and
      propleurum), and partly independent from these two character complexes (e.g., not
      connected profurca and propleuron). Strepsiptera are more derived than Coleoptera
      in some thoracic features (e.g., extremely enlarged metathorax) but have also
      preserved some plesiomorphic conditions (e.g., tegulae in both pterothoracic
      segments). All potential apomorphies of Mecopterida are missing in Strepsiptera.
      The last common ancestor of Coleopterida had already acquired posteromotorism but
      the wings were still largely unmodified. Several reductions in the mesothorax
      likely occurred independently.

PMID- 22583793
TI  - Butterfly morphology in a molecular age -- does it still matter in butterfly
      systematics?
AB  - We review morphological characters considered important for understanding
      butterfly phylogeny and evolution in the light of recent large-scale molecular
      phylogenies of the group. A number of the most important morphological works from
      the past half century are reviewed and morphological character evolution is
      reassessed based on the most recent phylogenetic results. In particular, higher
      level butterfly morphology is evaluated based on a very recent study combining an
      elaborate morphological dataset with a similar molecular one. Special attention
      is also given to the families Papilionidae, Nymphalidae and Hesperiidae which
      have all seen morphological and molecular efforts come together in large,
      combined works in recent years. In all of the examined cases the synergistic
      effect of combining elaborate morphological datasets with ditto molecular clearly
      outweigh the merits of either data type analysed on its own (even for 'genome
      size' molecular datasets). It is evident that morphology, far from being obsolete
      or arcane, still has an immensely important role to play in butterfly (and
      insect) phylogenetics. Not least because understanding morphology is essential
      for understanding and evaluating the evolutionary scenarios phylogenetic trees
      are supposed to illustrate.

PMID- 22583794
TI  - The female postabdomen and genitalia of the basal moth family Heterobathmiidae
      (Insecta: Lepidoptera): structure and phylogenetic significance.
AB  - Female Heterobathmia have the segments behind VIII forming a compact 'terminal
      unit' with a large saddle-shaped dorsal plate and a membranous ventroposterior
      surface bearing the separate gonopore and anus. While females of most of the nine
      known species are overall similar, Heterobathmia valvifer is unique amongst
      lepidopterans in possessing paired ventral appendages ('ovipositor valves')
      arising from the intersegmental groove following segment VIII; evidence from
      musculature contradicts an interpretation of these appendages structures as
      'true' ovipositor valves. The ventroposterior wall of the terminal unit in H.
      valvifer bears paired sclerites, possible homologues of the 'ventral rods' in
      basal Lepidoptera-Glossata. In Heterobathmia megadecella sclerites on paired
      longitudinal elevations in comparable positions probably are/include homologues
      of these sclerites. Their similarity with paired sclerotizations in the
      corresponding region of hydrobiosid caddisflies is noted. A prominent frame-like
      sclerotization in the genital chamber, located in front of the spermathecal duct
      origin, is present only in H. megadecella. Putative heterobathmiid autapomorphies
      include an enlarged 'subgenital plate' on venter VIII, absence of apophyses on
      segment VIII, shortened apophyses on the terminal unit, multilobed accessory
      glands (but their 'type 1' secretory epithelium is plesiomorphic at this level),
      a conspicuous papilla in the chamber cuticle bearing the opening of the ductus
      bursae on its apex, and inwards-pointing spines in the ductus bursae. A variably
      developed thickening of the anterior genital chamber intima is another putative
      family autapomorphy, while an extreme thickening of the posterior intima seen in
      Heterobathmia pseuderiocrania is not of general occurrence in heterobathmiids. A
      sistergroup relationship between Heterobathmiidae and Glossata is supported by
      their fully developed '2-compartment section' of the spermathecal duct and losses
      of some likely lepidopteran groundplan muscles.

PMID- 22583795
TI  - Body size and dispersal mode as key traits determining metacommunity structure of
      aquatic organisms.
AB  - Relationships between traits of organisms and the structure of their
      metacommunities have so far mainly been explored with meta-analyses. We compared
      metacommunities of a wide variety of aquatic organism groups (12 groups, ranging
      from bacteria to fish) in the same set of 99 ponds to minimise biases inherent to
      meta-analyses. In the category of passive dispersers, large-bodied groups showed
      stronger spatial patterning than small-bodied groups suggesting an increasing
      impact of dispersal limitation with increasing body size. Metacommunities of
      organisms with the ability to fly (i.e. insect groups) showed a weaker imprint of
      dispersal limitation than passive dispersers with similar body size. In contrast,
      dispersal movements of vertebrate groups (fish and amphibians) seemed to be
      mainly confined to local connectivity patterns. Our results reveal that body size
      and dispersal mode are important drivers of metacommunity structure and these
      traits should therefore be considered when developing a predictive framework for
      metacommunity dynamics.

PMID- 22583796
TI  - Reactive gliosis and neuroinflammation in rats with communicating hydrocephalus.
AB  - Reactive gliosis has been implicated in injury and recovery patterns associated
      with hydrocephalus. The roles that these mechanisms play in the pathophysiology
      of hydrocephalus are still not clear in terms of cytopathology and gene
      expression. In this paper, we investigated the relationship between reactive
      gliosis and neuroinflammation of hydrocephalic rats of different severity at both
      cellular and molecular levels. Therefore 35 adult SD (standard deviation) rats
      were randomly divided into the normal group (n=5), the sham operation group (n=5)
      and the model group (n=25). Hydrocephalic rat models were induced by
      intraventricular injections of 3% kaolin, and the ventricular dilatation was
      examined by MRI (magnetic resonance imaging) at 2-week postoperation. Then the
      model group was subdivided into the mild group (n=5), the moderate group (n=7)
      and the severe group (n=9) according to the degree of ventricular dilatation.
      While IL-18 (interlukin 18), GFAP (glial fibrillary acidic protein), and Iba-1
      (ionized calcium binding adaptor molecule-1) were detected by ELISA (enzyme
      linked immunosorbent assay), RT-PCR, immunohistochemistry, Western blot and
      correlation analysis were conducted at the same time. According to the result
      comparison between the normal group and the sham operation group, the ventricle
      of model group was obviously enlarged (P<0.01). The expression of GFAP and Iba-1
      was increased (P<0.05) in brain tissue of the model group and IL-18 was also
      increased in CSF (cerebrosinal fluid) sample of model group. It was revealed by
      correlation analysis that the increase was positively correlated with the
      severity of ventricular dilatation. CONCLUSION: These results indicate that
      gliosis and inflammation continue to rise dramatically in experimental
      hydrocephalus and can be regarded as the main factors of hydrocephalus.
      Regulating the level of gliosis and alleviating inflammation may provide new
      therapeutic methods of hydrocephalus.

PMID- 22583797
TI  - The soma and proximal dendrites of sympathetic preganglionic neurons innervating
      the major pelvic ganglion in female rats receive predominantly inhibitory inputs.
AB  - Sympathetic preganglionic neurons (SPNs) in the intermediolateral (IML) and
      dorsal commissural nucleus (DCN) of the thoracolumbar segments of the spinal cord
      contribute to the autonomic control of the pelvic visceral organs. We examined
      the morphology of these neurons at the light and electron microscopic level and
      quantified the boutons apposing the soma and proximal dendrites of the SPNs
      innervating the major pelvic ganglion (MPG) in female rats. The majority of these
      cells resided in the DCN (61.6+/-6.2%) and IML (33.2+/-4.4%) nuclei. Measurements
      of cell volume and shape revealed no differences between SPNs sampled from the
      DCN and IML populations. Ultrastructural studies of DCN and IML SPNs revealed
      that coverage of SPNs by synaptic inputs is sparse, with an average of 11.60+/
      2.41% of the soma membrane and 16.33+/-6.18% of proximal dendrites apposed by
      boutons, though some somata exhibited no synaptic coverage. Three distinct types
      of boutons were found to appose the SPN somata and dendrites. The putatively
      inhibitory F-type bouton covered a significantly greater percentage of membrane
      on the soma (8.48+/-2.12%) and dendrites (12.65+/-4.34%), than the S-type bouton,
      a putatively excitatory bouton, which only covered 2.94+/-0.70% of the somatic
      and 3.68+/-2.98% of the dendritic membranes. Boutons with dense-core vesicles
      were rare. Our results demonstrate that SPNs of the DCN and IML of female rats
      are similar morphologically, and that synaptic input on these cells, though
      sparse, is predominantly inhibitory.

PMID- 22583798
TI  - Characterization of a population of tyrosine hydroxylase-containing interneurons
      in the external plexiform layer of the rat olfactory bulb.
AB  - The olfactory bulb (OB) of mammals contains the major endogenous dopamine
      producing system in the forebrain. The vast majority of dopaminergic neurons
      consists of juxtaglomerular cells, which innervate the olfactory glomeruli and
      modulate the entrance of sensory information to the OB. Although dopaminergic
      juxtaglomerular cells have been widely investigated, the presence of dopaminergic
      interneurons other than juxtaglomerular cells has been largely unexplored. In
      this study, we analyze a population of tyrosine hydroxylase (TH)-containing
      interneurons located in the external plexiform layer (EPL) of the rat OB. These
      interneurons are GABAergic and morphologically heterogeneous. They have an axon
      and two to four dendrites running throughout the EPL. Frequently, they have
      appendages similar to spines in the dendrites and, sometimes, the distal portions
      of the dendritic branches show enlargements or swellings similar to varicosities.
      Contrary to other interneurons of the EPL, the TH-containing ones do not form
      dendro-dendritic synapses on principal cells and do not receive dendro-dendritic
      synapses from them. In fact, no synapses were found from the dendrites of these
      interneurons. When their dendrites are involved in synaptic contacts, they are
      always the postsynaptic element. They receive symmetrical and asymmetrical
      synapses from GABAergic and non-GABAergic axons of unidentified origin. Our data
      indicate that the local circuits of the EPL are more complex than previously
      thought. Although most of the interneurons of this layer establish dendro
      dendritic synaptic relationships with principal cells, the TH-containing
      interneurons constitute an exception to this rule, resembling interneurons from
      other cortical areas.

PMID- 22583799
TI  - The genetic architecture of flowering time and photoperiod sensitivity in maize
      as revealed by QTL review and meta analysis.
AB  - The control of flowering is not only important for reproduction, but also plays a
      key role in the processes of domestication and adaptation. To reveal the genetic
      architecture for flowering time and photoperiod sensitivity, a comprehensive
      evaluation of the relevant literature was performed and followed by meta
      analysis. A total of 25 synthetic consensus quantitative trait loci (QTL) and
      four hot-spot genomic regions were identified for photoperiod sensitivity
      including 11 genes related to photoperiod response or flower morphogenesis and
      development. Besides, a comparative analysis of the QTL for flowering time and
      photoperiod sensitivity highlighted the regions containing shared and unique QTL
      for the two traits. Candidate genes associated with maize flowering were
      identified through integrated analysis of the homologous genes for flowering time
      in plants and the consensus QTL regions for photoperiod sensitivity in maize (Zea
      mays L.). Our results suggest that the combination of literature review, meta
      analysis and homologous blast is an efficient approach to identify new candidate
      genes and create a global view of the genetic architecture for maize
      photoperiodic flowering. Sequences of candidate genes can be used to develop
      molecular markers for various models of marker-assisted selection, such as marker
      assisted recurrent selection and genomic selection that can contribute
      significantly to crop environmental adaptation.

PMID- 22583800
TI  - SPICE: discovery of phenotype-determining component interplays.
AB  - BACKGROUND: A latent behavior of a biological cell is complex. Deriving the
      underlying simplicity, or the fundamental rules governing this behavior has been
      the Holy Grail of systems biology. Data-driven prediction of the system
      components and their component interplays that are responsible for the target
      system's phenotype is a key and challenging step in this endeavor. RESULTS: The
      proposed approach, which we call System Phenotype-related Interplaying Components
      Enumerator (SPICE), iteratively enumerates statistically significant system
      components that are hypothesized (1) to play an important role in defining the
      specificity of the target system's phenotype(s); (2) to exhibit a functionally
      coherent behavior, namely, act in a coordinated manner to perform the phenotype
      specific function; and (3) to improve the predictive skill of the system's
      phenotype(s) when used collectively in the ensemble of predictive models. SPICE
      can be applied to both instance-based data and network-based data. When
      validated, SPICE effectively identified system components related to three target
      phenotypes: biohydrogen production, motility, and cancer. Manual results curation
      agreed with the known phenotype-related system components reported in literature.
      Additionally, using the identified system components as discriminatory features
      improved the prediction accuracy by 10% on the phenotype-classification task when
      compared to a number of state-of-the-art methods applied to eight benchmark
      microarray data sets. CONCLUSION: We formulate a problem--enumeration of
      phenotype-determining system component interplays--and propose an effective
      methodology (SPICE) to address this problem. SPICE improved identification of
      cancer-related groups of genes from various microarray data sets and detected
      groups of genes associated with microbial biohydrogen production and motility,
      many of which were reported in literature. SPICE also improved the predictive
      skill of the system's phenotype determination compared to individual classifiers
      and/or other ensemble methods, such as bagging, boosting, random forest, nearest
      shrunken centroid, and random forest variable selection method.

PMID- 22583801
TI  - Development and application of a 6.5 million feature Affymetrix Genechip(r) for
      massively parallel discovery of single position polymorphisms in lettuce (Lactuca
      spp.).
AB  - BACKGROUND: High-resolution genetic maps are needed in many crops to help
      characterize the genetic diversity that determines agriculturally important
      traits. Hybridization to microarrays to detect single feature polymorphisms is a
      powerful technique for marker discovery and genotyping because of its highly
      parallel nature. However, microarrays designed for gene expression analysis
      rarely provide sufficient gene coverage for optimal detection of nucleotide
      polymorphisms, which limits utility in species with low rates of polymorphism
      such as lettuce (Lactuca sativa). RESULTS: We developed a 6.5 million feature
      Affymetrix GeneChip(r) for efficient polymorphism discovery and genotyping, as
      well as for analysis of gene expression in lettuce. Probes on the microarray were
      designed from 26,809 unigenes from cultivated lettuce and an additional 8,819
      unigenes from four related species (L. serriola, L. saligna, L. virosa and L.
      perennis). Where possible, probes were tiled with a 2 bp stagger, alternating on
      each DNA strand; providing an average of 187 probes covering approximately 600 bp
      for each of over 35,000 unigenes; resulting in up to 13 fold redundancy in
      coverage per nucleotide. We developed protocols for hybridization of genomic DNA
      to the GeneChip(r) and refined custom algorithms that utilized coverage from
      multiple, high quality probes to detect single position polymorphisms in 2 bp
      sliding windows across each unigene. This allowed us to detect greater than
      18,000 polymorphisms between the parental lines of our core mapping population,
      as well as numerous polymorphisms between cultivated lettuce and wild species in
      the lettuce genepool. Using marker data from our diversity panel comprised of 52
      accessions from the five species listed above, we were able to separate
      accessions by species using both phylogenetic and principal component analyses.
      Additionally, we estimated the diversity between different types of cultivated
      lettuce and distinguished morphological types. CONCLUSION: By hybridizing genomic
      DNA to a custom oligonucleotide array designed for maximum gene coverage, we were
      able to identify polymorphisms using two approaches for pair-wise comparisons, as
      well as a highly parallel method that compared all 52 genotypes simultaneously.

PMID- 22583802
TI  - Treatment strategies for hepatocellular carcinoma in Japan.
AB  - The main methods of treatment for hepatocellular carcinoma (HCC) in Japan are
      hepatic resection, radiofrequency ablation (RFA) and transcatheter arterial
      chemoembolization (TACE). Meticulous follow up is then undertaken to check for
      recurrence, which is treated using repeated RFA or TACE. Hepatic arterial
      infusion chemotherapy has been introduced as treatment for advanced HCC, and the
      molecular-targeted drug sorafenib is also now available. Rigorous medical care
      using these treatment methods and early diagnosis mean that the prognosis for HCC
      in Japan is the best in the world. This paper reviews the treatment strategies
      for HCC in Japan.

PMID- 22583803
TI  - The human proteome - a scientific opportunity for transforming diagnostics,
      therapeutics, and healthcare.
AB  - A National Institutes of Health (NIH) workshop was convened in Bethesda, MD on
      September 26-27, 2011, with representative scientific leaders in the field of
      proteomics and its applications to clinical settings. The main purpose of this
      workshop was to articulate ways in which the biomedical research community can
      capitalize on recent technology advances and synergize with ongoing efforts to
      advance the field of human proteomics. This executive summary and the following
      full report describe the main discussions and outcomes of the workshop.

PMID- 22583804
TI  - Effects of chewing gum and time-on-task on alertness and attention.
AB  - RATIONALE: Chewing gum has been shown to reliably increase subjective alertness
      whereas the effects on attention are more variable. It has been suggested that
      chewing gum only enhances attention when the person has been performing a task
      for some time. OBJECTIVES: The current research aimed to investigate if time-on
      task trends enhancing effects of chewing gum could be observed in alertness and
      attention during and following chewing. METHODS: Study 1 used tests of reported
      mood, including reported mood, and tests of attention (categoric search, focussed
      attention, simple reaction time, and vigilance). These tasks were performed
      shortly after the start of chewing. Study 2 examined effects of previous and
      current chewing on reported alertness and the attention tests. RESULTS: Study 1
      showed that chewing gum increased reported alertness and hedonic tone and
      improved performance on the categoric search task. Chewing gum maintained
      reported alertness across sessions in study 2. In the first experimental session
      of study 2 gum improved categoric search performance, and during the second
      session gum broadened focus of attention and quickened vigilance reaction time.
      This effect on vigilance reaction time was moderated by time-on-task, with an
      initial negative effect being replaced by a positive effect. DISCUSSION: The
      results confirm the robust effect of chewing gum on reported alertness and show
      that changes in the effects of chewing gum on attention require further
      investigation. Future research may also determine underlying mechanisms for an
      alerting effect.

PMID- 22583805
TI  - New Danish reference values for spirometry.
AB  - INTRODUCTION: International recommendations state that reference values for lung
      function should derive from cross-sectional studies of healthy nonsmokers and be
      renewed from time to time because of cohort effect and newer, more accurate,
      technical equipment. In 1986, the Danish Lung Society published reference values
      for spirometry based on 570 individuals aged 30-70 years. OBJECTIVES: To produce
      new reference values for lung function and to extend the existing values by
      including individuals between 20 and 30 years of age and older than 70 years of
      age. METHODS: Two similar but independent studies was used: The 2001-2003
      examination of the Copenhagen City Heart Study and the 2003-2010 examination of
      the Copenhagen General Population Study. Of a total of 69 822 individuals, we
      included 11 288 healthy never-smoking white individuals to produce the reference
      values: 6307 women and 4981 men, 20 years of age or older with adequate lung
      function. RESULTS: We used sex-stratified multiple linear regression analysis to
      find prediction formulas for forced expiratory volume in 1 s (FEV1), forced vital
      capacity (FVC) and FEV1/FVC adjusted for age and height. The cutoff value of
      normal lung function was defined as the fifth percentile (also named the 5%
      quantile) according to gender, age and height. The robustness of the data was
      tested and validated in several ways. CONCLUSION: Compared with the 1986 data,
      our 2001-2010 material contributes with a substantial number of individuals in
      the more extreme groups of age and height, and in general, our dataset shows that
      in most subgroups, the lung function level has improved during the last two
      decades.

PMID- 22583807
TI  - A bacterial-two-hybrid selection system for one-step isolation of intracellularly
      functional Nanobodies.
AB  - Camel single-domain antibody fragments or Nanobodies, are practical in a wide
      range of applications. Their unique biochemical and biophysical properties permit
      an intracellular expression and antigen targeting. The availability of an
      efficient intracellular selection step would immediately identify the best
      intracellularly performing functional antibody fragments. Therefore, we assessed
      a bacterial-two-hybrid system to retrieve such Nanobodies. With GFP as an antigen
      we demonstrate that antigen-specific Nanobodies of sub-micromolar affinity and
      stability above 30 kJ/mol, at a titer of 10(-4) can be retrieved in a single-step
      selection. This was further proven practically by the successful recovery from an
      'immune' library of multiple stable, antigen-specific Nanobodies of good affinity
      for HIV-1 integrase or nucleoside hydrolase. The sequence diversity, intrinsic
      domain stability, antigen-specificity and affinity of these binders compare
      favorably to those that were retrieved in parallel by phage display pannings.

PMID- 22583806
TI  - Galectin-1, a gene preferentially expressed at the tumor margin, promotes
      glioblastoma cell invasion.
AB  - BACKGROUND: High-grade gliomas, including glioblastomas (GBMs), are recalcitrant
      to local therapy in part because of their ability to invade the normal brain
      parenchyma surrounding these tumors. Animal models capable of recapitulating
      glioblastoma invasion may help identify mediators of this aggressive phenotype.
      METHODS: Patient-derived glioblastoma lines have been propagated in our
      laboratories and orthotopically xenografted into the brains of immunocompromized
      mice. Invasive cells at the tumor periphery were isolated using laser capture
      microdissection. The mRNA expression profile of these cells was compared to
      expression at the tumor core, using normal mouse brain to control for host
      contamination. Galectin-1, a target identified by screening the resulting data,
      was stably over-expressed in the U87MG cell line. Sub-clones were assayed for
      attachment, proliferation, migration, invasion, and in vivo tumor phenotype.
      RESULTS: Expression microarray data identified galectin-1 as the most potent
      marker (p-value 4.0 x 10-8) to identify GBM cells between tumor-brain interface
      as compared to the tumor core. Over-expression of galectin-1 enhanced migration
      and invasion in vitro. In vivo, tumors expressing high galectin-1 levels showed
      enhanced invasion and decreased host survival. CONCLUSIONS: In conclusion, cells
      at the margin of glioblastoma, in comparison to tumor core cells, have enhanced
      expression of mediators of invasion. Galectin-1 is likely one such mediator.
      Previous studies, along with the current one, have proven galectin-1 to be
      important in the migration and invasion of glioblastoma cells, in GBM
      neoangiogenesis, and also, potentially, in GBM immune privilege. Targeting this
      molecule may offer clinical improvement to the current standard of glioblastoma
      therapy, i.e. radiation, temozolomide, anti-angiogenic therapy, and
      vaccinotherapy.

PMID- 22583808
TI  - Regulation of adherens junctions by Rho GTPases and p120-catenin.
AB  - The molecular mechanisms leading to tumor progression and acquisition of a
      metastatic phenotype are highly complex and only partially understood. The
      spatiotemporal regulation of E-cadherin-mediated adherens junctions is essential
      for normal epithelia function and tissue integrity. Perturbation of the E
      cadherin complex assembly is a key event in epithelial-mesenchymal transition and
      is directed by a huge number of mechanisms that differ greatly with regard to
      cell types and tissues. The reduction in intercellular adhesion interferes with
      tissue integrity and allows cancer cells to disseminate from the primary tumor
      thereby initiating cancer metastasis. In the present review we will summarize the
      current findings about the influence of Rho GTPases on the formation and
      maintenance of adherens junction and will then proceed to discuss the involvement
      of p120-catenin on cell-cell adhesion and tumor cell migration.

PMID- 22583809
TI  - Occurrence of pharmaceutical compounds in urban wastewater: removal, mass load
      and environmental risk after a secondary treatment--a review.
AB  - This review focuses on 118 pharmaceuticals, belonging to seventeen different
      therapeutic classes, detected in raw urban wastewater and effluent from an
      activated sludge system, a usual treatment adopted for urban wastewaters
      worldwide prior to final discharge into surface water bodies. Data pertaining to
      244 conventional activated sludge systems and 20 membrane biological reactors are
      analysed and the observed ranges of variability of each selected compound in
      their influent and effluent reported, with particular reference to the substances
      detected most frequently and in higher concentrations. A snapshot of the ability
      of these systems to remove such compounds is provided by comparing their global
      removal efficiencies for each substance. Where possible, the study then evaluates
      the average daily mass load of the majority of detected pharmaceuticals exiting
      the secondary treatment step. The final part of the review provides an assessment
      of the environmental risk posed by their presence in the secondary effluent by
      means of the risk quotient that is the ratio between the average pharmaceutical
      concentration measured in the secondary effluent and the predicted no-effect
      concentration. Finally, mass load rankings of the compounds under review are
      compared with those based on their risk level. This analysis shows that the
      highest amounts discharged through secondary effluent pertain to one
      antihypertensive, and several beta-blockers and analgesics/anti-inflammatories,
      while the highest risk is posed by antibiotics and several psychiatric drugs and
      analgesics/anti-inflammatories. These results are reported with a view to aiding
      scientists and administrators in planning measures aiming to reduce the impact of
      treated urban wastewater discharge into surface water bodies.

PMID- 22583810
TI  - Prostate angiosarcoma: is there any association with previous radiation therapy?
AB  - What's known on the subject? and What does the study add? Angiosarcomas are
      histological subtype of sarcomas and rarely involve the prostate gland. Only ten
      cases of prostate angiosarcoma have been reported in the literature to date.
      Occurrence of post-irradiation prostate angiosarcoma is rare considering the
      frequency of radiotherapy used for treatment of prostate adenocarcinoma. We
      provide a brief review of all cases of prostate angiosarcoma and describe the
      epidemiology, etiology, clinical presentation, histopathology, prognostic factors
      and current treatment options for prostate angiosarcoma. For the current review a
      literature search was carried out using Pubmed, EmBase, and Cochrane databases.
      All cases of prostate angioscaroma reported to date and observational studies
      evaluating the radiation associated cancer occurrence were reviewed. Despite the
      rarity, prostate angiosarcomas display remarkable clinical and pathological
      heterogeneity, and a treatment challenge. We found the association of prostate
      angiosarcoma with radiation therapy to be weak based upon the results from
      observational studies and case reports. Although radiation exposure has been
      suggested etiology of prostate angiosarcomas, assumption of such association is
      not supported by the current literature.

PMID- 22583811
TI  - Co-administration of morphine and oxycodone vaccines reduces the distribution of
      6-monoacetylmorphine and oxycodone to brain in rats.
AB  - Opioid conjugate vaccines have shown promise in animal models as a potential
      treatment for opioid addiction. Individual vaccines are quite specific and each
      targets only a limited number of structurally similar opioids. Since opioid users
      can switch or transition between opioids, we studied a bivalent immunization
      strategy of combining 2 vaccines that could target several of the most commonly
      abused opioids; heroin, oxycodone and their active metabolites. Morphine (M) and
      oxycodone (OXY) haptens were conjugated to keyhole limpet hemocyanin (KLH)
      through tetraglycine (Gly)(4) linkers at the C6 position. Immunization of rats
      with M-KLH alone produced high titers of antibodies directed against heroin, 6
      monoacetylmorphine (6-MAM) and morphine. Immunization with OXY-KLH produced high
      titers of antibodies against oxycodone and oxymorphone. Immunization with the
      bivalent vaccine produced consistently high antibody titers against both
      immunogens. Bivalent vaccine antibody titers against the individual immunogens
      were higher than with the monovalent vaccines alone owing, at least in part, to
      cross-reactivity of the antibodies. Administration of a single concurrent
      intravenous dose of 6-MAM and oxycodone to rats immunized with the bivalent
      vaccine increased 6-MAM, morphine and oxycodone retention in serum and reduced
      the distribution of 6-MAM and oxycodone to brain. Vaccine efficacy correlated
      with serum antibody titers for both monovalent vaccines, alone or in combination.
      Efficacy of the individual vaccines was not compromised by their combined use.
      Consistent with the enhanced titers in the bivalent group, a trend toward
      enhanced pharmacokinetic efficacy with the bivalent vaccine was observed. These
      data support the possibility of co-administering two or more opioid vaccines
      concurrently to target multiple abusable opioids without compromising the
      immunogenicity or efficacy of the individual components.

PMID- 22583812
TI  - Cross-protective immunity against o'nyong-nyong virus afforded by a novel
      recombinant chikungunya vaccine.
AB  - Emerging mosquito-borne alphavirus infections caused by chikungunya virus (CHIKV)
      or o'nyong-nyong virus (ONNV) are responsible for sporadic and sometimes
      explosive urban outbreaks. Currently, there is no licensed vaccine against either
      virus. We have developed a highly attenuated recombinant CHIKV candidate vaccine
      (CHIKV/IRES) that in preclinical studies was demonstrated to be safe, immunogenic
      and efficacious. In this study we investigated the potential of this vaccine to
      induce cross-protective immunity against the antigenically related ONNV. Our
      studies demonstrated that a single dose of CHIKV/IRES elicited a strong cross
      neutralizing antibody response and conferred protection against ONNV challenge in
      the A129 mouse model. Moreover, CHIKV/IRES immune A129 dams transferred
      antibodies to their offspring that were protective, and passively transferred
      anti-CHIKV/IRES immune serum protected AG129 mice, independently of a functional
      IFN response. These findings highlight the potential of the CHIKV/IRES vaccine to
      protect humans against not only CHIKV but also against ONNV-induced disease.

PMID- 22583813
TI  - Student nurse socialisation in compassionate practice: a Grounded Theory study.
AB  - Compassionate practice is expected of Registered Nurses (RNs) around the world
      while at the same time remaining a contested concept. Nevertheless, student
      nurses are expected to enact compassionate practice in order to become RNs. In
      order for this to happen they require professional socialisation within
      environments where compassion can flourish. However, there is concern that
      student nurse socialisation is not enabling compassion to flourish and be
      maintained upon professional qualification. In order to investigate this further,
      a glaserian Grounded Theory study was undertaken using in-depth, digitally
      recorded interviews with student nurses (n=19) at a university in the north of
      England during 2009 and 2010. Interviews were also undertaken with their nurse
      teachers (n=5) and data from National Health Service (NHS) patients (n=72,000)
      and staff (n=290,000) surveys were used to build a contextual picture of the
      student experience. Within the selected findings presented, analysis of the data
      indicates that students aspire to the professional ideal of compassionate
      practice although they have concerns about how compassionate practice might fit
      within the RN role because of constraints on RN practice. Students feel
      vulnerable to dissonance between professional ideals and practice reality. They
      experience uncertainty about their future role and about opportunities to engage
      in compassionate practice. Students manage their vulnerability and uncertainty by
      balancing between an intention to uphold professional ideals and challenge
      constraints, and a realisation they might need to adapt their ideals and conform
      to constraints. This study demonstrates that socialisation in compassionate
      practice is compromised by dissonance between professional idealism and practice
      realism. Realignment between the reality of practice and professional ideals, and
      fostering student resilience, are required if students are to be successfully
      socialised in compassionate practice and enabled to retain this professional
      ideal within the demands of 21st century nursing.

PMID- 22583814
TI  - Master's level education in Jordan: a qualitative study of key motivational
      factors and perceived impact on practice.
AB  - AIM: To explore key motivational factors of Jordanian nurses to undertake a
      Master's degree and explore perceived impact on practice. BACKGROUND: In Jordan,
      there are postgraduate educational programmes offering a Master's degree in
      clinical nursing for registered nurses. These programmes are intended to prepare
      nurses to practise at an advanced level as potential clinical nurse specialists.
      Little is known about the motivation of nurses to undertake such Master's degree
      preparation programmes and their perceived impact on practice. METHODS: Using an
      ethnographic design, narratives from semi-structured interviews with participants
      (n=37) from five Jordanian hospitals and two public universities were collected
      and thematically analysed. FINDINGS: Four main themes emerged from the data: self
      development; broadening career opportunities; developing practice; and the
      perceived impact of Master's level nurses on practice. CONCLUSION: The majority
      of Jordanian nurses chose to undertake a Master's degree because of a desire for
      self and practice development. The majority of participants referred to M-level
      nurses in terms of knowledge transfer, highlighting their clinical teaching and
      in-service education activities. M-level nurses were also associated with
      managerial and supervisory roles in clinical practice. Controversy over the
      impact of M-level nurses in enhancing patient care is not limited to the
      Jordanian setting. Future research needs to focus on comparative studies between
      nurses with M-level qualifications and experienced nurses without either M-level
      qualifications or specialist courses to establish if there is any significant
      relationship between practice performance and educational preparation and
      experience. Evaluation research could be undertaken for the purpose of developing
      measurable and observable criteria related to educational and skill based
      outcomes.

PMID- 22583815
TI  - Tongue cancer in young patients: case report of a 26-year-old patient.
AB  - INTRODUCTION: This article presents the case of a 26-year-old woman with tongue
      cancer. The median age at the diagnosis of the tongue's cancer is 61 years. Only
      approximately 2% of patients are diagnosed before the age of 35. CASE
      PRESENTATION: Our patient survived acute myeloid leukemia (AML) before her second
      year. She had been having recurrent, poorly healing aphtae on the right side of
      the tongue for a period of months before the symptoms of the tongue cancer
      appeared. As a treatment a partial glossectomy was conducted on the right side
      and a neck dissection of levels I-III. Than a reconstruction of the tongue with a
      radialis free vascularised flap from left side was performed. DISCUSSION: It
      should be always looked for the causal factor in young patients with a neoplasm.
      There is strong evidence for second malignant neoplasms in survivors of childhood
      cancer.

PMID- 22583816
TI  - Effect of specific activation of gamma-aminobutyric acid receptor in vivo on
      oxidative stress-induced damage after extended hepatectomy.
AB  - AIM:   gamma-Aminobutyric acid (GABA) is a multifunctional molecule with various
      physiological effects throughout the body. The regulation of GABA receptor
      (GABAR) plays a key role in reducing the damage mediated by oxidative stress
      (OS). Extended hepatectomy causes fatal OS-induced injury in the liver remnant.
      We aimed to investigate the effect of a GABAR agonist in extended hepatectomy.
      METHODS:   Saline or a GABAR agonist (43.56 nmol/g bodyweight of muscimol) was
      administrated intravenously at 4 h preoperatively. C57BL/6 mice were divided into
      three groups: laparotomy only, 90% hepatectomy with saline and 90% hepatectomy
      with a GABAR agonist. Liver samples were obtained at 6 h after surgery. RESULTS: 
      Survival curves were prolonged by the GABAR agonist. Histopathological findings
      and biochemical profiles showed that the GABAR agonist reduced liver damage.
      Immunohistological assessment demonstrated that the GABAR agonist prevented
      apoptotic induction. As shown by 4-hydroxynonenal, which reflects OS-induced
      damage, 90% hepatectomy caused OS and the GABAR agonist reduced OS. We measured
      ataxia-telangiectasia mutated kinase (ATM), H2AX, Akt and free radical scavenging
      enzymes because they may be affected by GABAR regulation, and found that Akt was
      greatly decreased after 90% hepatectomy, but it recovered with the GABAR agonist.
      CONCLUSION:   GABAR is activated by a specific agonist in the liver in vivo. This
      activation reduces OS-mediated damage after extended hepatectomy in vivo, and the
      mechanism via an Akt-dependent pathway may be a key.

PMID- 22583817
TI  - Use of glucometer and fasting blood glucose as screening tools for diabetes
      mellitus type 2 and glycated haemoglobin as clinical reference in rural community
      primary care settings of a middle income country.
AB  - BACKGROUND: Thailand is considered to be a middle income country, and to control
      and prevent type 2 diabetes mellitus (T2DM) is one of the main concerns of the
      Thai Ministry of Public Health (MoPH). Screening for T2DM and care for T2DM
      patients has been integrated into the primary health care system, especially in
      rural areas. The intention of this investigation is to link public health
      research at the academic level with the local health authorities of a district of
      a north-eastern province of the country. METHODS: Epidemiological methods were
      applied to validate the screening tools fasting capillary blood glucose (CBG),
      measured by glucometer and venous blood for the determination of plasma glucose
      (VPG), used for screening for T2DM among asymptomatic villagers. For assessing
      the validity of these two methods glycated haemoglobin (HbA1c) values were
      determined and used as the 'clinical reference'. RESULTS: All together 669
      villagers were investigated. Determinations of CBG and VPG resulted in suspected
      T2DM cases, with 7.3% when assessed by CBG and 6.4% by VPG using a cutoff point
      of 7 mmol/L (126 mg/dl). Taking HbA1c determinations with a cutoff point of 7%
      into account, the proportion of T2DM suspected participants increased to 10.4%.
      By estimating sensitivity, specificity and the positive predictive value of CBG
      and VPG against the 'clinical reference' of HbA1c, sensitivity below 50% for both
      screening methods has been observed. The positive predictive value was determined
      to be 58.5% for CBG and 56.8% for VPG. The specificity of the two screening tests
      was over 96%. CONCLUSIONS: The low sensitivity indicates that using fasting CBG
      or VPG as a screening tool in the field results in a high proportion of diseased
      individuals remaining undetected. The equally low positive predictive values
      (below 60%) indicate a high working load for the curative sector in investigating
      suspected T2DM cases to determine whether they are truly diseased or false
      positive cases according to the screening method. Further implications of the
      results and the controversial discussion related to the use of HbA1c as clinical
      evidence for suffering from T2DM are also discussed.

PMID- 22583818
TI  - Estimating RNA-quality using GeneChip microarrays.
AB  - BACKGROUND: Microarrays are a powerful tool for transcriptome analysis. Best
      results are obtained using high-quality RNA samples for preparation and
      hybridization. Issues with RNA integrity can lead to low data quality and failure
      of the microarray experiment. RESULTS: Microarray intensity data contains
      information to estimate the RNA quality of the sample. We here study the
      interplay of the characteristics of RNA surface hybridization with the effects of
      partly truncated transcripts on probe intensity. The 3'/5' intensity gradient,
      the basis of microarray RNA quality measures, is shown to depend on the degree of
      competitive binding of specific and of non-specific targets to a particular
      probe, on the degree of saturation of the probes with bound transcripts and on
      the distance of the probe from the 3'-end of the transcript. Increasing degrees
      of non-specific hybridization or of saturation reduce the 3'/5' intensity
      gradient and if not taken into account, this leads to biased results in common
      quality measures for GeneChip arrays such as affyslope or the control probe
      intensity ratio. We also found that short probe sets near the 3'-end of the
      transcripts are prone to non-specific hybridization presumable because of
      inaccurate positional assignment and the existence of transcript isoforms with
      variable 3' UTRs. Poor RNA quality is associated with a decreased amount of RNA
      material hybridized on the array paralleled by a decreased total signal level.
      Additionally, it causes a gene-specific loss of signal due to the positional bias
      of transcript abundance which requires an individual, gene-specific correction.
      We propose a new RNA quality measure that considers the hybridization mode.
      Graphical characteristics are introduced allowing assessment of RNA quality of
      each single array ('tongs plot' and 'degradation hook'). Furthermore, we suggest
      a method to correct for effects of RNA degradation on microarray intensities.
      CONCLUSIONS: The presented RNA degradation measure has best correlation with the
      independent RNA integrity measure RIN, and therefore presents itself as a
      valuable tool for quality control and even for the study of RNA degradation. When
      RNA degradation effects are detected in microarray experiments, a correction of
      the induced bias in probe intensities is advised.

PMID- 22583819
TI  - A network perspective on metabolic inconsistency.
AB  - BACKGROUND: Integrating gene expression profiles and metabolic pathways under
      different experimental conditions is essential for understanding the coherence of
      these two layers of cellular organization. The network character of metabolic
      systems can be instrumental in developing concepts of agreement between
      expression data and pathways. A network-driven interpretation of gene expression
      data has the potential of suggesting novel classifiers for pathological cellular
      states and of contributing to a general theoretical understanding of gene
      regulation. RESULTS: Here, we analyze the coherence of gene expression patterns
      and a reconstruction of human metabolism, using consistency scores obtained from
      network and constraint-based analysis methods. We find a surprisingly strong
      correlation between the two measures, demonstrating that a substantial part of
      inconsistencies between metabolic processes and gene expression can be understood
      from a network perspective alone. Prompted by this finding, we investigate the
      topological context of the individual biochemical reactions responsible for the
      observed inconsistencies. On this basis, we are able to separate the differential
      contributions that bear physiological information about the system, from the
      unspecific contributions that unravel gaps in the metabolic reconstruction. We
      demonstrate the biological potential of our network-driven approach by analyzing
      transcriptome profiles of aldosterone producing adenomas that have been obtained
      from a cohort of Primary Aldosteronism patients. We unravel systematics in the
      data that could not have been resolved by conventional microarray data analysis.
      In particular, we discover two distinct metabolic states in the adenoma
      expression patterns. CONCLUSIONS: The methodology presented here can help
      understand metabolic inconsistencies from a network perspective. It thus serves
      as a mediator between the topology of metabolic systems and their dynamical
      function. Finally, we demonstrate how physiologically relevant insights into the
      structure and dynamics of metabolic networks can be obtained using this novel
      approach.

PMID- 22583820
TI  - Guidelines adherence and hypertension control at a tertiary hospital in Malaysia.
AB  - RATIONALE, AIMS AND OBJECTIVES: Existing literature suggests that doctors' poor
      adherence with guidelines is one of the major contributing factors to suboptimal
      control of hypertension. This study aims to evaluate doctors' adherence with
      Malaysian clinical practice guideline (CPG 2008) in a tertiary care hospital, and
      factors associated with guideline adherence and hypertension control. METHODS:
      This was a cross-sectional study conducted at Hospital Pulau Pinang, Penang,
      Malaysia. Prescriptions written by 26 enrolled doctors to 650 established
      hypertensive outpatients (25 prescriptions per enrolled doctor) were noted on
      visit 1 along with patients' demographic and clinical data. The noted
      prescriptions were classified either as compliant or non-compliant to CPG (2008).
      Five hundred twenty (80%) of the enrolled patients (20 patients per enrolled
      doctor) were followed for one more visit. Blood pressure (BP) noted on visit 2
      was related to the prescription written on visit 1. SPSS 16 (SPSS Inc., Chicago,
      IL, USA) was used for data analysis. RESULTS: Three hundred forty-nine (67.1%)
      patients received guidelines compliant pharmacotherapy. In multivariate analysis,
      hypertension clinic had significant negative association with guidelines
      adherence. Two hundred sixty-five patients (51%) were at goal BP on visit 2. In
      multivariate analysis, angiotensin-converting enzyme inhibitors and guidelines
      adherence had significant positive, while renal disease, diabetes mellitus and
      diabetic clinic had significant negative association with hypertension control.
      CONCLUSIONS: An overall fair level of adherence with guidelines and better
      control of hypertension was observed. Guidelines compliant practices resulted in
      better control of hypertension. The gaps between what guidelines recommend and
      clinical practice were especially seen in the pharmacotherapy of uncomplicated
      hypertension and hypertension with diabetes mellitus and renal disease.

PMID- 22583821
TI  - Protein kinase C-delta (PKC-delta) and PKC-alpha mediate Ca(2+)-dependent
      increases in CNP mRNA in human vascular cells.
AB  - C type natriuretic peptide (CNP) functions as a paracrine/autocrine
      vasoprotectant. CNP mRNA is up-regulated in human vascular smooth muscle cells
      (SMC) by PDGF-BB via a protein kinase C (PKC)-dependent pathways, and by general
      PKC activation with phorbol myristate acetate (PMA). In this report we examine
      the calcium dependence and isotype specificity of these PKC/CNP pathways. The PKC
      delta-specific inhibitor rottlerin blocked the increase in CNP mRNA and
      immunoreactive CNP following treatment of aortic SMC (AoSMC) with PDGF-BB. A 300
      400-fold PMA-induced elevation of CNP transcript levels in AoSMC and a ~40-fold
      increase in human aortic endothelial cells (HAEC) were reduced by PKC-alpha- and
      PKC-delta-, but not PKC-beta-specific inhibitors. siRNA silencing of PKC-delta
      reduced PDGF-, but not PMA-stimulated CNP transcript in SMC. Inhibition of
      intracellular Ca(2+) mobilization abolished a PMA-stimulated increase in CNP
      transcript in both SMC and HAEC. The results of this study show that PDGF
      increases CNP in SMC via a protein kinase C-delta-dependent pathway. In contrast,
      PMA increases CNP expression using PKC-alpha- and PKC-delta-pathways in both SMC
      and HAEC. A 8-10-fold greater PMA-induced increase in CNP transcript in SMC than
      in HAEC suggests that smooth muscle cells could be selectively targeted for CNP
      up-regulation by PKC-alpha- and PKC-delta-activators.

PMID- 22583822
TI  - An interview with the authors of "Is there a U-shaped curve of A1c vs.
      mortality?".

PMID- 22583823
TI  - Ectopic expression of a bacterium NhaD-type Na+/H+ antiporter leads to increased
      tolerance to combined salt/alkali stresses.
AB  - AaNhaD, a gene isolated from the soda lake alkaliphile Alkalimonas amylolytica,
      encodes a Na(+) /H(+)  antiporter crucial for the bacterium's resistance to
      salt/alkali stresses. However, it remains unknown whether this type of bacterial
      gene may be able to increase the tolerance of flowering plants to salt/alkali
      stresses. To investigate the use of extremophile genetic resources in higher
      plants, transgenic tobacco BY-2 cells and plants harboring AaNhaD were generated
      and their stress tolerance was evaluated. Ectopic expression of AaNhaD enhanced
      the salt tolerance of the transgenic BY-2 cells in a pH-dependent manner.
      Compared to wild-type controls, the transgenic cells exhibited increased Na(+) 
      concentrations and pH levels in the vacuoles. Subcellular localization analysis
      indicated that AaNhaD-GFP fusion proteins were primarily localized in the
      tonoplasts. Similar to the transgenic BY-2 cells, AaNhaD-overexpressing tobacco
      plants displayed enhanced stress tolerance when grown in saline-alkali soil.
      These results indicate that AaNhaD functions as a pH-dependent tonoplast Na(+)
      /H(+)  antiporter in plant cells, thus presenting a new avenue for the genetic
      improvement of salinity/alkalinity tolerance.

PMID- 22583824
TI  - Investigation on BRCA1 SNPs and its effects on mastitis in Chinese commercial
      cattle.
AB  - The main objective of this study was to investigate whether the bovine breast
      cancer 1 (BRCA1) gene was associated with mastitis resistance in Chinese
      commercial cattle. A total of 51 SNPs were screened from public data resources
      and DNA sequencing. Three SNPs (c.5682G>C,c.26198C>T and c.46126G>T) were
      genotyped by polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) and created restriction site PCR (CRS-PCR) methods and 21 combinations
      of these SNPs were observed. The single SNP and their genetic effects on somatic
      cell score (SCS) were evaluated and a significant association with SCS was found
      in c.46126G>T. The mean SCS of individuals with genotype KK was significantly
      lower than those of genotypes KL and LL. The results of combined genotypes
      analysis of three SNPs showed that HHLLNN genotype with the highest SCS was
      easily for the mastitis susceptibility, whereas GGKKMM genotype with the lowest
      SCS was favorable for the mastitis resistance. The information provided in the
      present study will be very useful for improving mastitis resistance in dairy
      cattle by marker-assisted selection (MAS).

PMID- 22583825
TI  - Association study of microRNA polymorphisms with hepatocellular carcinoma in
      Korean population.
AB  - BACKGROUND: Recent studies have suggested that common genetic polymorphisms alter
      the processing of microRNA (miRNA) and may be associated with the development and
      progression of cancer. PATIENTS AND METHODS: The association of miRNA
      polymorphisms with HCC survival was analyzed in 159 HCC patients and 201 controls
      by the polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP) method. RESULTS: The risk of HCC was significantly lower for the miR
      499A>G, AG+GG in HCC patients (AOR=0.603, 95% CI=0.370-0.984) and hepatitis B
      virus (HBV)-related HCC patients (AOR=0.561, 95% CI 0.331-0.950). In addition,
      the risk of HCC was significantly lower for the miR-149C>T, CT and CT+CC in HCC
      patients (CT; AOR=0.542, 95% CI=0.332-0.886, CT+CC; AOR=0.536, 95% CI=0.335
      0.858) and HBV-related HCC patients (CT: AOR=0.510, 95% CI 0.305-0.854, CT+CC:
      AOR=0.496, 95% CI 0.302-0.813). The miR-149C>T polymorphism was also associated
      with survival rate of HCC patients in OKUDA II stage. CONCLUSIONS: miR-149C>T and
      miR-499A>G were associated with HBV-related HCC. Further studies on larger
      populations will need to be conducted to confirm these results.

PMID- 22583826
TI  - Overexpression of the Qc-SNARE gene OsSYP71 enhances tolerance to oxidative
      stress and resistance to rice blast in rice (Oryza sativa L.).
AB  - OsSYP71 is an oxidative stress and rice blast response gene that encodes a Qc
      SNARE protein in rice. Qc-SNARE proteins belong to the superfamily of SNAREs
      (soluble N-ethylmaleimide-sensitive factor attachment protein receptors), which
      function as important components of the vesicle trafficking machinery in
      eukaryotic cells. In this paper, 12 Qc-SNARE genes were isolated from rice, and
      expression patterns of 9 genes were detected in various tissues and in seedlings
      challenged with oxidative stresses and inoculated with rice blast. The expression
      of OsSYP71 was clearly up-regulated under these stresses. Overexpression of
      OsSYP71 in rice showed more tolerance to oxidative stress and resistance to rice
      blast than wild-type plants. These results indicate that Qc-SNAREs play an
      important role in rice response to environmental stresses, and OsSYP71 is useful
      in engineering crop plants with enhanced tolerance to oxidative stress and
      resistance to rice blast.

PMID- 22583827
TI  - Influence of functional genetic polymorphism (-590C/T) in non-small cell lung
      cancer (NSCLC) development: the paradoxal role of IL-4.
AB  - Lung cancer is the leading cause of death by cancer in the world, originating
      about 17.5% of total deaths from cancer (1.18 million). Inflammation plays an
      important role in the pathogenesis of lung cancer. IL-4 is an anti-inflammatory
      cytokine, which reduces the production of proinflammatory cytokines by monocytes
      and with direct antiproliferative effects in some tumors. The polymorphism 
      590C/T SNP is a C to T transition in the -590 position of the promoter region of
      the IL-4 gene. The aim of this study was to evaluate the influence of this
      polymorphism in the susceptibility to NSCLC. DNA was extracted from peripheral
      blood of 1060 individuals (391 patients diagnosed with NSCLC and a control group
      of 669 individuals without cancer). The characterization of IL-4 -590C/T
      genotypes was performed by PCR-RFLP (BsmFI). The -590C/T polymorphism genotypes
      were classified as low (CC) and high expression (TT). The frequencies obtained
      for the CC and TT genotypes were 90.1% and 9.9%, respectively, in the control
      group and 92.9% and 7.1%, respectively, in the case group. The analysis of the TT
      and CC genotype frequencies in the two groups showed a statistically significant
      difference in its distribution, indicating a protection of 80% for the
      development of NSCLC, type epidermoid in individuals with the TT genotype when
      compared with individuals with CC genotype (P=0.024, OR=0.221: 95% CI=0.053
      0.928). We present for the first time that increased expression of IL-4
      associated with the TT genotype may contribute to immune surveillance during
      NSCLC development.

PMID- 22583828
TI  - Array-CGH characterization of a de novo t(X;Y)(p22;q11) in a female with short
      stature and mental retardation.
AB  - We report the clinical and molecular investigations in a girl with 46,X,
      X,+der(X)t(X;Y)(p22;q11) de novo karyotype who presented an intricate phenotype
      characterized by mental retardation and facial dysmorphisms in combination with
      short stature. The structure of the derivative X chromosome was studied using BAC
      array-CGH which disclosed the Xp22 breakpoint between the STS and the VCX3A gene
      and the presence of the Yq11.1qter chromosome. It is common that females with
      Xp;Yq translocations present only short stature and are normal in every other
      aspect. Thus, this would be the first case in which a girl with Xp;Yq
      translocation presents an unusual phenotype with intermediate male clinical
      features with Xp;Yq translocations. The risk of developing gonadoblastoma in
      females with Y chromosome material is also discussed and, to this effect,
      different explanations related to this apparent variation are also presented.

PMID- 22583829
TI  - Role of toll-like receptor 4 on the immune escape of human oral squamous cell
      carcinoma and resistance of cisplatin-induced apoptosis.
AB  - BACKGROUND: Toll-like receptor 4 (TLR4) is expressed on immune cells as a sensor
      that recognizes lipopolysaccharide (LPS), a microbial conserved component. It has
      recently been determined that the expression of TLR4 is also found in various
      types of tumor cells. Cisplatin is a widely used chemotherapeutic agent for oral
      squamous cell carcinoma (OSCC) treatment. However, the mechanisms responsible for
      cisplatin resistance are not well understood. RESULTS: The present study was
      designed to elucidate the role of TLR4 expression in human OSCC regarding immune
      escape and apoptotic resistance to cisplatin. TLR4 and the myeloid
      differentiation primary response gene 88 (MyD88) were highly expressed in OSCC
      cell lines. Upon LPS stimulation both NF-kappaB and p38 MAPK pathways were
      activated in OSCC cell lines, followed by the production of large quantities of
      IL-6, IL-8 and VEGF compared with human immortalized oral epithelia cells
      (HIOECs). OSCC cell lines were found to be resistant to cisplatin-mediated
      apoptosis after pretreatment with LPS. CONCLUSIONS: Our results suggested that
      TLR4 was functionally expressed in human OSCC cells and development of resistance
      to cisplatin in human OSCC might occur through the mechanism involving TLR4 and
      its signaling pathway. Suppression of TLR4 and its signaling pathway might thus
      elevate sensitivity to cisplatin and potentially help improve the prognosis of
      patients with OSCC.

PMID- 22583830
TI  - Posterior semicircular canal occlusion for intractable benign positional vertigo:
      outcome in 55 ears in 53 patients operated upon over 20 years.
AB  - OBJECTIVE: To report the outcome of posterior semicircular canal occlusion
      surgery for intractable benign positional vertigo, regarding vertigo cure rate
      and hearing and balance outcomes. METHODS: Retrospective review of 53 patients
      presenting with benign positional vertigo, unresponsive to repositioning
      manoeuvres, who eventually underwent posterior canal occlusion, over a 20 year
      period. RESULTS: From 1991 to 2011, 5364 benign positional vertigo patients were
      treated in our balance disorders clinic; 53 of those who failed to respond to
      repositioning underwent posterior canal occlusion. All 53 were cured of their
      benign positional vertigo. Nine suffered some symptomatic permanent hearing loss
      (>20 dB at low and >25 dB at high frequencies). Ten patients suffered caloric
      vestibular function deterioration, with mild but permanent subjective imbalance
      in five; a further 10 patients with no post-operative caloric test changes also
      had some permanent imbalance. Benign positional vertigo later developed in the
      operated ear lateral canal in two patients and in the opposite ear posterior
      canal in eight patients. Two patients needed bilateral sequential posterior canal
      occlusion. CONCLUSION: Posterior canal occlusion is a highly effective treatment
      for intractable benign positional vertigo, with what is probably an acceptable
      risk to hearing and balance: five of six patients will have no hearing problem
      and nine of 10 no balance problem after surgery.

PMID- 22583831
TI  - Adult mice voluntarily progress to nicotine dependence in an oral self-selection
      assay.
AB  - Nicotine has both rewarding and aversive properties in rodents, as shown by
      intravenous self-administration, intracranial self-stimulation, and conditioned
      place preference experiments. However, high throughput models of nicotine reward
      have not been developed in mice. In previous two-bottle studies, mice often chose
      to drink less from the nicotine bottle than from the water bottle, which raises
      the question whether these paradigms provide a model of the reinforcing
      properties of oral nicotine. We hypothesized that previous two-bottle choice
      paradigms included factors (such as the brief duration of trials, the addition of
      flavorings to both bottles, water bottles located relatively close to each other,
      etc.) that may have obstructed the formation of a learned association between the
      taste of nicotine and its delayed pharmacological effects. Here we show that a
      paradigm designed to simplify the acquisition of a learned association resulted
      in nicotine consumption by various strains and sexes that diverged progressively
      over a period of seven weeks. The strain and sex with the highest nicotine
      consumption (C57BL/6J females) showed steady and statistically significant
      increases in nicotine consumption throughout this period. C57BL/6J females were
      clearly responding to the reinforcing properties of nicotine because they chose
      to drink over 70% of their fluids from the nicotine bottle. Moreover, they became
      nicotine dependent, as shown by highly significant nicotine withdrawal symptoms
      after the nicotine bottle was removed. The strain and sex with the lowest
      consumption (A/J males) showed a significant decrease in nicotine consumption,
      and by the end of the experiment were drinking only 24% of their fluids from the
      nicotine bottle.

PMID- 22583832
TI  - Poly(ethylene glycol) diacrylate-supported ionogels with consistent capacitive
      behavior and tunable elastic response.
AB  - Harnessing the many favorable properties of ionic liquids in a solid electrolyte
      thin film form is desirable for a host of electrical energy storage applications,
      including electrochemical double layer capacitors. Using a cross-linked polymer
      matrix to provide structural support, freestanding ionogel materials can be
      achieved with a wide range of polymer weight fractions. Compression testing and
      impedance spectroscopy have been used to characterize the mechanical and
      electrical responses of ionogels containing between 4.9 and 44.7 wt %
      poly(ethylene glycol) diacrylate. Although the elastic modulus of these solid
      electrolyte materials is observed to vary by more than 4 orders of magnitude
      within the composition range studied, concomitant changes in gel ionic
      conductivity and double layer capacitance were much less dramatic. 

PMID- 22583834
TI  - A comparative study of finger pulp reconstruction using arterialised venous
      sensate flap and insensate flap from forearm.
AB  - OBJECTIVE: The aim of this study was to investigate the feasibility of finger
      pulp reconstruction using arterialised venous flaps from forearm and compare the
      outcomes of arterialised venous sensate flap and insensate flap. METHODS: Twenty
      seven arterialised venous flaps were reviewed retrospectively in the
      reconstruction of finger pulp defects in 23 patients, including 15 sensate flaps
      (sensate group) and 12 insensate flaps (insensate group). Nine flaps in this
      series were harvested from the dorsal aspect of the forearm and the other 18 were
      harvested from the volar aspect. Standardised assessment of outcomes in terms of
      objective sensory recovery, pinch power of the reconstructed digits, cold
      intolerance and time of returning to work was completed. RESULTS: All flaps
      survived completely. Twenty-six flaps were available for follow-up of more than 9
      months (mean, 15.4 months). Almost all the flaps in the sensate group obtained
      normal sensation, while most cases of the insensate group only achieved
      protective sensation. Cold intolerance was present in most cases of the insensate
      group in comparison with the sensate group with only one case suffering from
      slight cold intolerance. There was no significant difference of pinch power
      between the two groups. All the patients were contented with the aesthetic
      outcomes of the surgery. CONCLUSION: The arterialised venous sensate flap from
      forearm is a practical alternative for finger pulp reconstruction with
      satisfactory functional and aesthetic outcomes. The forearm region can be an
      acceptable donor site for arterialised venous sensate flap in the reconstruction
      of larger finger pulp defect.

PMID- 22583833
TI  - IOP induces upregulation of GFAP and MHC-II and microglia reactivity in mice
      retina contralateral to experimental glaucoma.
AB  - BACKGROUND: Ocular hypertension is a major risk factor for glaucoma, a
      neurodegenerative disease characterized by an irreversible decrease in ganglion
      cells and their axons. Macroglial and microglial cells appear to play an
      important role in the pathogenic mechanisms of the disease. Here, we study the
      effects of laser-induced ocular hypertension (OHT) in the macroglia, microglia
      and retinal ganglion cells (RGCs) of eyes with OHT (OHT-eyes) and contralateral
      eyes two weeks after lasering. METHODS: Two groups of adult Swiss mice were used:
      age-matched control (naive, n=9); and lasered (n=9). In the lasered animals, both
      OHT-eyes and contralateral eyes were analyzed. Retinal whole-mounts were
      immunostained with antibodies against glial fibrillary acid protein (GFAP),
      neurofilament of 200 kD (NF-200), ionized calcium binding adaptor molecule (Iba
      1) and major histocompatibility complex class II molecule (MHC-II). The GFAP
      labeled retinal area (GFAP-RA), the intensity of GFAP immunoreaction (GFAP-IR),
      and the number of astrocytes and NF-200 + RGCs were quantified. RESULTS: In
      comparison with naive: i) astrocytes were more robust in contralateral eyes. In
      OHT-eyes, the astrocyte population was not homogeneous, given that astrocytes
      displaying only primary processes coexisted with astrocytes in which primary and
      secondary processes could be recognized, the former having less intense GFAP-IR
      (P<0.001); ii) GFAP-RA was increased in contralateral (P<.05) and decreased in
      OHT-eyes (P <0.001); iii) the mean intensity of GFAP-IR was higher in OHT-eyes
      (P<0.01), and the percentage of the retinal area occupied by GFAP+ cells with
      higher intensity levels was increased in contralateral (P=0.05) and in OHT-eyes
      (P<0.01); iv) both in contralateral and in OHT-eyes, GFAP was upregulated in
      Muller cells and microglia was activated; v) MHC-II was upregulated on macroglia
      and microglia. In microglia, it was similarly expressed in contralateral and OHT
      eyes. By contrast, in macroglia, MHC-II upregulation was observed mainly in
      astrocytes in contralateral eyes and in Muller cells in OHT-eyes; vi) NF-200+
      RGCs (degenerated cells) appeared in OHT-eyes with a trend for the GFAP-RA to
      decrease and for the NF-200+RGC number to increase from the center to the
      periphery (r= -0.45). CONCLUSION: The use of the contralateral eye as an internal
      control in experimental induction of unilateral IOP should be reconsidered. The
      gliotic behavior in contralateral eyes could be related to the immune response.
      The absence of NF-200+RGCs (sign of RGC degeneration) leads us to postulate that
      the MHC-II upregulation in contralateral eyes could favor neuroprotection.

PMID- 22583836
TI  - Phylogenetic diversity and the functioning of ecosystems.
AB  - Phylogenetic diversity (PD) describes the total amount of phylogenetic distance
      among species in a community. Although there has been substantial research on the
      factors that determine community PD, exploration of the consequences of PD for
      ecosystem functioning is just beginning. We argue that PD may be useful in
      predicting ecosystem functions in a range of communities, from single-trophic to
      complex networks. Many traits show a phylogenetic signal, suggesting that PD can
      estimate the functional trait space of a community, and thus ecosystem
      functioning. Phylogeny also determines interactions among species, and so could
      help predict how extinctions cascade through ecological networks and thus impact
      ecosystem functions. Although the initial evidence available suggests patterns
      consistent with these predictions, we caution that the utility of PD depends
      critically on the strength of phylogenetic signals to both traits and
      interactions. We advocate for a synthetic approach that incorporates a deeper
      understanding of how traits and interactions are shaped by evolution, and outline
      key areas for future research. If these complexities can be incorporated into
      future studies, relationships between PD and ecosystem function bear promise in
      conceptually unifying evolutionary biology with ecosystem ecology.

PMID- 22583835
TI  - Molecular structures of fluid phase phosphatidylglycerol bilayers as determined
      by small angle neutron and X-ray scattering.
AB  - We have determined the molecular structures of commonly used
      phosphatidylglycerols (PGs) in the commonly accepted biologically relevant fluid
      phase. This was done by simultaneously analyzing small angle neutron and X-ray
      scattering data, with the constraint of measured lipid volumes. We report the
      temperature dependence of bilayer parameters obtained using the one-dimensional
      scattering density profile model - which was derived from molecular dynamics
      simulations - including the area per lipid, the overall bilayer thickness, as
      well as other intrabilayer parameters (e.g., hydrocarbon thickness). Lipid areas
      are found to be larger than their phosphatidylcholine (PC) counterparts, a result
      likely due to repulsive electrostatic interactions taking place between the
      charged PG headgroups even in the presence of sodium counterions. In general, PG
      and PC bilayers show a similar response to changes in temperature and chain
      length, but differ in their response to chain unsaturation. For example, compared
      to PC bilayers, the inclusion of a first double bond in PG lipids results in a
      smaller incremental change to the area per lipid and bilayer thickness. However,
      the extrapolated lipid area of saturated PG lipids to infinite chain length is
      found to be similar to that of PCs, an indication of the glycerol-carbonyl
      backbone's pivotal role in influencing the lipid-water interface.

PMID- 22583837
TI  - Sublethal effects in Atlantic salmon (Salmo salar) exposed to mixtures of copper,
      aluminium and gamma radiation.
AB  - The present study was designed to investigate the effects in presmolt of Atlantic
      salmon (Salmo salar) exposed to copper (Cu), aluminium (Al) and gamma radiation,
      individually or in combination. Fish were exposed for 48 h to metals added to
      lake water; 10, 40 and 80 MUg Cu/L, 250 MUg Al/L and a combination of 40 MUg Cu/L
      and 250 MUg Al/L. In addition, gamma radiation (4-70 mGy delivered over 48 h) was
      added as an additional exposure stressor. Selected endpoints were chosen to
      reveal different toxic mechanisms and included Cu and Al accumulation on gills,
      blood chemistry and haematological variables (plasma sodium and chloride,
      haematocrit, glucose), hepatic levels of reduced and oxidised glutathione (GSH
      and GSSG) and hepatic transcriptional response of glutathione peroxidase (GPx),
      gamma-glutamylcysteine synthetase (GCS), metallothionein (MT) and ubiquitin.
      Exposure to Cu alone resulted in gill accumulation of Cu, reduction of plasma
      ions and increased transcriptional response of GPx, MT and ubiquitin. Exposure to
      Al alone reduced plasma ion levels but did not affect any of the hepatic
      biomarkers except for ubiquitin. The combined metal exposure (Cu + Al) altered
      the GSH levels, however GPx and MT were not affected suggesting a different mode
      of detoxification in the combined exposure. Gamma radiation appeared to influence
      GSH and ubiquitin levels. The observed effects seemed to be both stressor and
      concentration dependent.

PMID- 22583838
TI  - Long-term death and recurrence in patients with acute venous thromboembolism: the
      MASTER registry.
AB  - BACKGROUND: The long-term clinical outcome of VTE has been essentially assessed
      in cohorts of selected patients. The aim of this multicenter registry was to
      prospectively assess the long-term clinical outcome in a cohort of unselected
      patients with objectively confirmed acute VTE. MATERIALS AND METHODS: Death and
      VTE recurrence at 24 months were the main study outcomes. Univariate and
      multivariate survival analyses were performed according to the Kaplan-Meyer and
      Cox proportional hazard model, respectively. RESULTS: 2119 patients with acute
      VTE were included in the registry: 1541 (72.7%) with deep vein thrombosis, 206
      (9.7%) with pulmonary embolism and 372 (17.6%) with both. Information about death
      was available in 2021 patients (95.4%) and about recurrence in 1988 patients
      (93.8%). 167 patients (4.55% patient-year) died during follow-up. After adjusting
      for age, cancer (Hazard ratio [HR]: 7.2; 95%CI 4.8-10.8), long-term heparin
      treatment (HR: 2.5; 95%CI 1.8-3.5), in-hospital management of VTE (HR: 2.0; 95%CI
      1.3-3.0), and ileo-caval thrombosis (HR: 1.7; 95%CI 1.2-2.4) were found to be
      independent predictors of death. 124 (3.63% patient-year) patients had a VTE
      recurrence during follow-up. In-hospital management of VTE (HR: 1.8; 95%CI 1.2
      2.9), male gender (HR: 1.7; 95%CI 1.2-2.4) were independent risk factors for
      recurrent VTE. Cancer (HR: 1.6; 95%CI 1.0-2.8) showed a trend for increased risk
      of VTE recurrence (p=0.056). The reported rate of major bleeding was 2.5%.
      CONCLUSIONS: In a large cohort of unselected VTE patients, cancer, ileo-caval
      thrombosis, long-term heparin treatment and in-hospital management were
      associated with increased mortality during long-term follow-up. In-hospital
      management, male gender were associated with an increased risk of VTE recurrence.

PMID- 22583839
TI  - Zinc diet and Alzheimer's disease: a systematic review.
AB  - OBJECTIVES: This paper reviews evidence of an association between zinc (Zn)
      nutrition and Alzheimer's disease (AD) or age-associated cognitive decline. The
      involvement of zinc in the pathology of AD has been reported hundreds of times.
      It is, however, still a matter of debate  whether the disease progression can be
      influenced by modifying zinc in the diet. METHODS: We searched Medline, Embase,
      Biosis, ALOIS, the Cochrane central register of controlled trials, the Cochrane
      database of systematic reviews, and different publisher databases, and included 
      studies that dealt with zinc in the diet and AD or cognitive decline in elderly
      subjects. RESULTS: Fifty-five studies met the inclusion criteria. Neither
      randomized-controlled trials nor observational studies provide conclusive
      evidence whether Zn in the diet is associated  with cognitive decline or AD. Case
      control and autopsy studies suggest decreased systemic and increased brain Zn
      levels, respectively. DISCUSSION: The current state of evidence does not allow
      conclusions to be drawn on whether supplementation of Zn is beneficial for the 
      prevention or treatment of AD, although a subclinical deficiency appears common
      in the elderly and subjects with AD. Dietary studies with animals suggest that
      the impact of dietary Zn on cognitive performance depend on additional nutrients.
      Further studies are necessary to determine whether  Zn deficiency is a risk
      factor for AD in general terms or under certain dietary circumstances only.

PMID- 22583840
TI  - Testicular histopathology as a predictor of a positive sperm retrieval in men
      with non-obstructive azoospermia.
AB  - WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The management of
      patients with non-obstructive azoospermia (NOA) involves testicular sperm
      extraction (TESE or microdissection TESE) combined with intracytoplasmic sperm
      injection (ICSI). Sperm retrieval is successful in up to 50% of men with NOA;
      however, there is no single clinical finding or investigation that can accurately
      predict a positive outcome. Several studies have concluded that testicular biopsy
      is the best predictor of a successful TESE. The present study shows that the
      strongest predictor of the success of TESE is when tubules with mature
      spermatozoa (Johnsen score >=8) are found in the histopathology specimen,
      irrespective of the overall state of spermatogenesis. The findings suggest that a
      lower limit threshold value of 2% of tubules with spermatogenesis in the
      histopathology specimen will result in a positive sperm retrieval. However, it is
      not practical to perform a diagnostic biopsy before TESE because this would mean
      that patients undergo two surgeries, which adds to the cost and increases the
      complications. The diagnostic biopsy is best coupled with an initial TESE before
      starting the ICSI cycle. Based on the findings of the histopathology specimen,
      patients may be then offered a repeat TESE if more sperm is needed on the day of
      ovum pick-up and ICSI. Also, if the initial TESE was negative, the biopsy result
      will help in the decision to offer a repeat TESE. This regimen is more cost
      effective because the ICSI cycle will be started only if adequate sperm is
      retrieved. OBJECTIVE: To assess whether testicular histopathology can predict the
      outcome of testicular sperm extraction (TESE) in men with non-obstructive
      azoospermia (NOA) and therefore the role of preoperative diagnostic testis
      biopsy. PATIENTS AND METHODS: The study comprised a retrospective analysis of 388
      patients with azoospermia who were referred from 2005 to 2010. Information
      collected included a clinical history and an examination including age and
      testicular size, serum follicle-stimulating hormone, two semen analyses and
      testicular histology collected at the time of surgical sperm retrieval (TESE or
      microdissection TESE). RESULTS: In total, 388 patients with a mean (range) age of
      37 (18-66) years were included in the present study. Based on the history,
      clinical and laboratory findings, 112 patients had obstructive azoospermia and
      276 patients had NOA. All patients in the obstructed group had a positive sperm
      retrieval. The sperm retrieval rate for the NOA group was 50%. An analysis of the
      results showed that the best predictor of a positive sperm retrieval was when
      tubules with mature spermatozoa were seen at biopsy, irrespective of the overall
      state of spermatogenesis (P < 0.001). CONCLUSIONS: The presence of tubules with
      spermatazoa on biospy is the best predictor of a positive surgical sperm
      retrieval in patients with NOA. The diagnostic biopsy is best coupled with an
      initial TESE before starting the intracytoplasmic sperm injection (ICSI) cycle.
      Based on the findings of the histopathology specimen, patients may be offered a
      repeat TESE if more sperm is needed on the day of ovum pick-up and ICSI, or a
      redo TESE if the initial TESE was negative.

PMID- 22583841
TI  - Comparison of clinicians and an artificial neural network regarding accuracy and
      certainty in performance of visual field assessment for the diagnosis of
      glaucoma.
AB  - PURPOSE: To compare clinicians and a trained artificial neural network (ANN)
      regarding accuracy and certainty of assessment of visual fields for the diagnosis
      of glaucoma. METHODS: Thirty physicians with different levels of knowledge and
      experience in glaucoma management assessed 30-2 SITA Standard visual field
      printouts that included full Statpac information from 99 patients with
      glaucomatous optic neuropathy and 66 healthy subjects. Glaucomatous eyes with
      perimetric mean deviation values worsethan -10 dB were not eligible. The fields
      were graded on a scale of 1-10, where 1 indicated healthy with absolute
      certaintyand 10 signified glaucoma; 5.5 was the cut-off between healthy and
      glaucoma. The same fields were classified by a previously trained ANN. The ANN
      output was transformed into a linear scale that matched the scale used in the
      subjective assessments. Classification certainty was assessed using a
      classification error score. RESULTS: Among the physicians, sensitivity ranged
      from 61% to 96% (mean 83%) and specificity from 59% to 100% (mean 90%). Our ANN
      achieved 93% sensitivity and 91% specificity, and it was significantly more
      sensitive than the physicians (p < 0.001) at a similar level of specificity. The
      ANN classification error score was equivalent to the top third scores of all
      physicians, and the ANN never indicated a high degree of certainty for any of its
      misclassified visual field tests. CONCLUSION: Our results indicate that a trained
      ANN performs at least as well as physicians in assessments of visual fields for
      the diagnosis of glaucoma.

PMID- 22583842
TI  - Demonstration of anatomical reentrant tachycardia circuit in verapamil-sensitive
      atrial tachycardia originating from the vicinity of the atrioventricular node.
AB  - BACKGROUND: The anatomical location of the reentry circuit in verapamil-sensitive
      atrial tachycardia originating from the vicinity of atrioventricular node (V-AT)
      is not well clarified. OBJECTIVE: To define the reentry circuit of V-AT. METHODS:
      In 17 patients with V-AT, rapid atrial pacing at a rate 5 beats/min faster than
      the tachycardia rate was delivered from multiple sites of the right atrium (RA)
      during tachycardia to define the direction of the proximity of the slow
      conduction area of the reentry circuit. After identification of manifest
      entrainment and orthodromic capture of the earliest atrial activation site
      (EAAS), radiofrequency energy was delivered starting at a site 2 cm away from the
      EAAS in the direction of the pacing site. Radiofrequency energy application site
      was then gradually advanced toward EAAS until the termination of tachycardia to
      define the entrance of the slow conduction area. RESULTS: The EAAS was
      orthodromically captured by pacing delivered from one of the high anterolateral
      RA (n = 6), high posteroseptal RA (n = 9), and RA appendage (n = 2).
      Radiofrequency energy delivery to the site, 10.1 +/- 2.8 mm away from the EAAS,
      terminated V-AT immediately after the onset of delivery (2.9 +/- 1.0 seconds).
      The successful ablation site located outside the Koch's triangle, being more
      distant from the His bundle site than the EAAS (12.4 +/- 2.9 vs 6.4 +/- 1.9 mm; P
      <.0001). CONCLUSION: The reentry circuit of V-AT located outside the Koch's
      triangle. V-AT was eliminated by the radiofrequency energy delivered to the
      entrance of the reentry circuit, which was more distant from the His bundle site
      than the EAAS, under the navigation of entrainment.

PMID- 22583843
TI  - High-frequency stimulation of the atria increases early recurrence following
      pulmonary vein isolation in patients with persistent atrial fibrillation.
AB  - BACKGROUND: High-frequency stimulation (HFS) of the atria induces atrial
      fibrillation (AF) when applied during sinus rhythm and elicits a parasympathetic
      response when delivered at sites where ganglionated plexi (GPs) are located.
      However, little is known about its impact after an electrophysiological study.
      OBJECTIVE: To evaluate the impact of HFS on the short-term and long-term outcomes
      after the ablation of persistent AF. METHODS: Thirty consecutive patients with
      persistent or long-standing persistent AF were randomly assigned to either
      receive HFS of the left atrium (n = 15) or not (n = 15) during their
      electrophysiological studies. Patients receiving HFS were examined to determine
      whether or not a vagal response was elicited by the HFS at sites where GPs were
      located before and after conventional pulmonary vein isolation without any
      ablation targeting the GPs. Patients not receiving the HFS underwent the ablation
      procedure alone. The rate of recurrence of AF within 3 months of the procedure
      (early recurrence [ER]) and the frequency of that occurring after that period
      (late recurrence) were compared between the patient groups. RESULTS: The
      incidence of ER occurred more frequently in patients with HFS than in those
      without (80% vs 40%; P = .015), whereas the occurrence of late recurrence was
      similar between the 2 groups (27% vs 33%; P = .73). In the HFS group, the number
      of GPs decreased from 3.4 +/- 1.1 to 1.5 +/- 0.8 after the pulmonary vein
      isolation (P < .0001), and the decrease was smaller in the patients experiencing
      ER than in those without. CONCLUSION: HFS increases the incidence of ER in
      patients with persistent AF despite a partial GP modification resulting from the
      pulmonary vein isolation.

PMID- 22583844
TI  - QRS prolongation induced by cardiac resynchronization therapy correlates with
      deterioration in left ventricular function.
AB  - BACKGROUND: The benefits of cardiac resynchronization in inducing reverse
      ventricular remodeling in patients with left ventricular (LV) systolic
      dysfunction have been well established. Still, up to 30% of the patients fail to
      derive significant improvement from this therapy. A subset of "nonresponders"
      experience deterioration in LV function following cardiac resynchronization
      therapy (CRT). Characteristics of this patient population, however, have not been
      studied. OBJECTIVE: To determine characteristics of patients who experience
      deterioration in LV function following CRT. METHODS: Clinical,
      electrocardiographic, and echocardiographic data were collected in 856
      consecutive patients presenting for a new CRT device. For inclusion, all patients
      had an LV ejection fraction '40%, a QRS duration '120 ms, and available baseline
      and follow-up echocardiograms and electrocardiograms. Deterioration in LV
      function was defined as an absolute decrease of 5% or greater in ejection
      fraction from baseline. Multivariate models were constructed to identify
      variables significantly associated with deterioration. RESULTS: A total of 507
      patients met inclusion criteria, of which 60 (11.8%) met criteria for
      deterioration. Patients with deterioration were more likely to be men (86.7% vs
      66.9%; P = .002), have a non-left bundle branch block morphology (41.7% vs 23.7%;
      P = .001), and a history of atrial fibrillation (66.7% vs 51.7%; P = .03). On
      comparing the pre-CRT QRS duration with the first biventricular-paced QRS
      duration post-CRT implant, it was found that patients with LV deterioration had
      significant QRS widening than did those without deterioration (ms) (+3.9 +/- 34.1
      vs -9.0 +/- 27.4, P = .007, respectively). In multivariate analysis, QRS widening
      indexed to the baseline QRS duration was significantly associated with LV
      deterioration (odds ratio 1.14 [1.06-1.23]; P = .001). CONCLUSION: QRS widening
      is associated with deterioration in LV function following CRT.

PMID- 22583845
TI  - Reconstruction of scalp defects with the radial forearm free flap.
AB  - BACKGROUND: Advanced and recurrent cutaneous squamous cell carcinoma of the scalp
      and forehead require aggressive surgical excision often resulting in complex
      defects requiring reconstruction. This study evaluates various microvascular free
      flap reconstructions in this patient population, including the rarely utilized
      radial forearm free flap. PATIENTS AND METHODS: A retrospective review of
      patients undergoing free flap surgeries (n = 47) of the scalp between 1997 and
      2011 were included. Patients were divided primarily into two cohorts: a new
      primary lesion (n = 21) or recurrence (n = 26). Factors examined include patient
      demographics, indication for surgery, defect, type of flap used, complications
      (major and minor), and outcomes. RESULTS: The patients were primarily male (n =
      34), with a mean age of 67 years (25-91). A total of 58 microvascular free flap
      reconstructions were performed (radial forearm free flap: n = 28, latissimus
      dorsi: n = 20, rectus abdominis: n = 9, scapula: n = 1). Following reconstruction
      with a radial forearm free flap, duration of hospitalization was shorter (P =
      0.04) and complications rates were similar (P = 0.46). Donor site selection
      correlated with defect area (P < 0.001), but not with the extent of skull defect
      (P = 0.70). Larger defect areas correlated with higher complications rates (P =
      0.03) and longer hospitalization (P = 0.003). Patients were more likely to
      require multiple reconstructions if referred for a recurrent lesions (P = 0.01)
      or received prior radiation therapy (P = 0.02). CONCLUSION: Advanced and
      recurrent malignancies of the scalp are aggressive and challenging to treat. The
      radial forearm free flap is an underutilized free flap in the reconstruction of
      complex scalp defects.

PMID- 22583846
TI  - Huperzine A-phospholipid complex-loaded biodegradable thermosensitive polymer gel
      for controlled drug release.
AB  - The huperzine A-phospholipid complex loaded biodegradable thermosensitive PLGA
      PEG-PLGA polymer gel was studied as injectable implant system for controlled
      release of huperzine-A (HA). First, HA molecules were successfully incorporated
      into the soybean phosphatidylcholine (SP) molecules to form the huperzine-A
      soybean phosphatidylcholine complexes (HA-SPC), which was proved by FT-IR, DSC,
      XRD, solubility study, TEM, etc. The results indicated that hydrogen bonds and
      electrostatic interaction between HA and SP molecules play an important role in
      the formation of HA-SPC. Secondly, the HA-SPC was loaded into biodegradable PLGA
      PEG-PLGA thermosensitive gel as injectable implant material to control the
      release of HA. The in vitro and in vivo drug release behaviors of the prepared
      products were studied. The in vitro release studies demonstrated that the HA-SPC
      loaded gel significantly reduced the initial burst of drug release and extended
      the release period to about 2 weeks. The in vivo pharmacokinetics study of HA-SPC
      loaded gel in rabbits showed that plasma concentration of HA (2.54-0.15ng/mL) was
      detected for nearly 2 weeks from delivery systems upon single subcutaneous
      injection. What's more, the in vitro release pattern correlated well with the in
      vivo pharmacokinetics profile. The present study indicates that HA-SPC loaded
      PLGA-PEG-PLGA thermal gel may be an attractive candidate vehicle for controlled
      HA release.

PMID- 22583847
TI  - Stabilized terbutaline submicron drug aerosol for deep lungs deposition: drug
      assay, pulmonokinetics and biodistribution by UHPLC/ESI-q-TOF-MS method.
AB  - Terbutaline submicron particles (SMUTBS) were prepared by nanoprecipitation
      technique followed by spray drying for deep lungs deposition. Inhalable SMUTBS
      particles were 645.16 nm of diameter with 0.11MUm of MMAD, suggested for better
      aerosol effects. Both submicron and micron-sized TBS particles were administered
      in rodents administered via major delivery routes, and their biological effects
      were compared by using UHPLC/ESI-q-TOF-MS method. TBS was found stable in all
      exposed conditions with 96.28-99.0% of recovery and <4.34% of accuracy (CV). An
      inhalation device was designed and validated to deliver medicines to lungs, which
      was found best at dose level of 25mg for 30 min of fluidization. Both submicron
      and micron particles were compared for in vivo lung deposition and a 1.67 fold
      increase in concentration was observed for SMUTBS exposed by inhalation.
      Optimized DPI formulation contained lesser fraction of ultrafine particle (<500
      nm) with the major fraction of submicron particles (>500 nm), advocated for
      better targeting to lungs. UHPLC/ESI-q-TOF-MS confirmed that designed submicron
      particles has been successfully delivered to the lungs. From tongue to lungs, the
      landing of pulmonary medicines can be improved by submicronization technology.

PMID- 22583848
TI  - The STEP (safety and toxicity of excipients for paediatrics) database. Part 1-A
      need assessment study.
AB  - Excipients that are commonly used in adult medicines have been associated with
      elevated toxicological risks and safety issues in children. However, the
      information available on their acceptability for paediatric age groups is sparse
      and distributed over various sources. Hence, European (Eu) and United States (US)
      Paediatric Formulation Initiatives (PFIs) are collaboratively creating a STEP
      database. Because the development of database is a costly and time consuming
      venture, it is important to capture the requirements from the potential users and
      identify at an early stage the content and features that will serve the specific
      needs so that they can incorporate into the databases as it is developed. AIM: To
      assess the need of STEP database, to determine the database content and structure
      that meets the needs of the potential users. METHOD: A global survey was
      conducted via EuPFI website and email invitations, targeting a representative
      cross section of industrial, regulatory, academic and clinical professionals, to
      capture the database requirements. RESULT: The survey revealed (1) the potential
      users of this database, (2) the excipients' toxicity and safety information
      needs, (3) the content and structure preferred for the database. Majority of
      respondents favoured the development of STEP database and reported that it would
      be a valuable resource. CONCLUSION AND FUTURE WORK: The survey emphasized the
      need for STEP database and thus leads us to development of pilot database to
      assess the feasibility of developing such a database.

PMID- 22583849
TI  - Formation of ultrafine deferasirox particles via rapid expansion of supercritical
      solution (RESS process) using Taguchi approach.
AB  - The poor water solubility of many drugs is a challenge in pharmaceutical
      research. Recently, there have been great interests in finding environmentally
      friendly methods producing fine particles of pharmaceutical products for
      applications in pharmaceutical engineering. A promising method to improve the
      bioavailability of pharmaceutical agents is the rapid expansion of supercritical
      solutions. Deferasirox (DFS), a tridentate chelator, requires two molecules for
      iron (III) coordination. The bioavailability (the percentage of the drug absorbed
      compared to its initial dosage) is limited by this insolubility. The effect of
      four different RESS parameters including, extraction temperature (308-318K),
      extraction pressure (140-200 bar), effective nozzle diameter (500-1200 MUm), with
      and without cosolvents were investigated on the size and morphology of the
      precipitated particles of deferasirox based on Taguchi design. The results show
      great reduction in the size of the precipitated particles of deferasirox (50 nm-5
      MUm) via RESS process compared with the original particles of deferasirox (5-500
      MUm).

PMID- 22583850
TI  - Encapsulation of azithromycin into polymeric microspheres by reduced pressure
      solvent evaporation method.
AB  - Azithromycin loaded microspheres with blends of poly-l-lactide and ploy-D,L
      lactide-co-glycolide as matrices were prepared by the atmosphere-solvent
      evaporation (ASE) and reduced pressure-solvent evaporation (RSE) method. Both the
      X-ray diffraction spectra and DSC thermographs demonstrated that poly-L-lactide
      existed in a crystalline form in the ASE microspheres, while an amorphous form
      was present in the RSE formulations. Besides, solvent removal at atmosphere gave
      microspheres of porous and rough surfaces, but smooth surfaces appeared in the
      RSE microspheres. The incorporation efficiency as well as the burst release
      (cumulative release in the first 24h) in the ASE formulations was 39.94 +/- 1.18%
      and 23.96 +/- 2.01% respectively, yet the encapsulation efficiency of the
      microspheres fabricated under 385 mmHg was high up to 57.19 +/- 3.81% and the
      burst release was 4.12 +/- 0.15%. The in vitro drug release studies indicated
      that the ASE microspheres presented a zero-order profile; while the RSE
      formulations followed first-order kinetics. Other factors including
      solidification time, temperature, drug to polymer ratio and pH value of the
      continuous phase could also influence the physicochemical characteristics and
      release profiles of microspheres. In conclusion, the overall improvement of
      microspheres in appearance, encapsulation efficiency and controlled drug release
      through the RSE method could be easily fulfilled under optimal preparation
      conditions.

PMID- 22583851
TI  - Miscibility analysis of particulate solid dispersions prepared by electrospray
      deposition.
AB  - Physical characteristics of solid dispersions were investigated using
      carbamazepine (CBZ) and prednisolone (PDN) as model drugs, and poly(vinyl
      pyrrolidone) and Eudragit as polymeric excipients. Electrospray method provided
      particulate formulations, of which the particle size was typically in the order
      of micrometers, when the polymer concentration of the solution used for the
      preparation was below 2% (w/v). Decrease of the solution concentration and flow
      rate resulted in a decrease in the particle diameter, as theoretically expected.
      Also, the particle size could be reduced to 400 nm by increasing the conductivity
      of the solution by the addition of salts. When poly(vinyl pyrrolidone) K90 was
      used as an excipient, CBZ was homogeneously loaded up to ca. 40%, and if a
      greater amount was added, the excess CBZ was separated as a pure crystalline
      phase. PDN was homogeneously loaded up to ca. 60%. However, in contrast to CBZ,
      excess PDN maintained the amorphous state, even when a greater amount was added.
      The separated excess PDN phase was crystallized in the heating process during
      thermal analysis. In addition to the thermodynamic factor, there seems to be a
      dynamic factor to separate drug phase from the excipient phase, depending on
      their molecular weight and miscibility during the electrospray deposition
      process. The mechanism for particle formation by electrospray deposition is
      discussed with emphasis on the miscibility between drug and excipient.

PMID- 22583852
TI  - Analysis of Florida and New York state hospital discharges suggests that carotid
      stenting in symptomatic women is associated with significant increase in
      mortality and perioperative morbidity compared with carotid endarterectomy.
AB  - BACKGROUND: Although large randomized studies have established the efficacy and
      safety of carotid endarterectomy (CEA) and, recently, carotid artery stenting
      (CAS), the under-representation of women in these trials leaves the comparison of
      risks to benefits of performing these procedures on women an open question. To
      address this issue, we reviewed the hospital outcomes and delineated patient
      characteristics predicting outcome in women undergoing carotid interventions
      using New York and Florida statewide hospital discharge databases. METHODS: We
      analyzed in-hospital mortality, postoperative stroke, cardiac postoperative
      complications, and combined postoperative stoke and mortality in 20,613 CEA or
      CAS hospitalizations for the years 2007 to 2009. Univariate and multiple logistic
      regression analyses of variables were performed. RESULTS: CEA was performed in
      16,576 asymptomatic and 1744 symptomatic women and CAS in 1943 asymptomatic and
      350 symptomatic women. Compared with CAS, CEA rates, in asymptomatic vs
      symptomatic, were significantly lower for in-hospital mortality (0.3% vs 0.8% and
      0.4% vs 3.4%), stroke (1.5% vs 2.6% and 3.5% vs 9.4%), and combined
      stroke/mortality (1.7% vs 3.1% and 3.8% vs 10.9%). In cohorts matched by
      propensity scores, the same trend favoring CEA remained significant in
      symptomatic women. There was no difference in cardiac complication rates among
      asymptomatic women, but among symptomatic woman cardiac complications were more
      frequent after CAS (10.6% vs 6.5%; P = .0077). Among symptomatic women, the
      presence of renal disease, coronary artery disease, or age >=80 years increased
      the risk of CAS over CEA threefold for the composite end point of stroke or
      death. For asymptomatic women only in those with coronary artery disease or
      diabetes, there was a statistical difference in the composite mortality/stroke
      rates favoring CEA (1.9% vs 3.3% and 1.7% vs 3.4%, respectively). After adjusting
      for relevant clinical and demographic risk factors and hospital annual volume,
      for CAS vs CEA, the risk of the composite end point of stroke or mortality was
      1.7-fold higher in symptomatic and 3.4-fold higher in asymptomatic patients.
      Medicaid insurance, symptomatic patient, history of cancer, and presence of heart
      failure on admission were among other strong predictors of composite
      stroke/mortality outcome. CONCLUSIONS: Databases reflecting real-world practice
      performance and management of carotid disease in women suggest that CEA compared
      with CAS has overall better perioperative outcomes in women. Importantly, CAS is
      associated with significantly higher morbidity in certain clinical settings and
      this should be taken into account when choosing a revascularization procedure.

PMID- 22583853
TI  - Transcatheter arterial revascularization outcomes at vascular and general surgery
      teaching hospitals and nonteaching hospitals are comparable.
AB  - BACKGROUND: Outcomes following transcatheter interventions at vascular and
      general surgery teaching hospitals (STH) are unknown. We examine whether surgery
      training programs influence clinically relevant outcomes after commonly performed
      endovascular procedures. METHODS: Using an all-payer inpatient care database from
      2008, we selected adults who underwent either endovascular carotid stenting,
      endografting of descending thoracic aortic aneurysm, endovascular abdominal
      aortic aneurysm repair, or peripheral arterial revascularization. Patients were
      stratified by procedures completed at Surgery Teaching (Participate in
      Accreditation Council for Graduate Medical Education [ACGME]-accredited vascular
      and general surgery programs), STH, or nonteaching hospitals (NTH). Hierarchical
      regression models assessed adverse outcomes and in-hospital mortality among
      groups. RESULTS: Of the 175,698 records, 44% of the patients were treated at STH,
      while 56% underwent procedures at NTH. The adjusted odds ratio of any
      complication or mortality at STH and NTH were similar. Transfers, weekend
      admissions, and nonelective cases were higher at STH (P < .001, respectively).
      Paradoxically, STH treated fewer patients with more than three comorbidities
      compared with NTH (STH: 47% vs NTH: 53%; P < .001). Surgical teaching status did
      not lower the adjusted odds of mortality for any procedure. Moreover, the
      occurrence of any complication (adjusted odds ratios, 0.9; 95% confidence
      interval, .82-1.14; P = .69) and mortality (adjusted odds ratios, 0.9; 95%
      confidence interval, .74-1.22; P = .67) were equivalent between vascular and
      general STH. CONCLUSIONS: Following commonly performed transcatheter vascular
      procedures, and despite more transfers, weekend admissions, and nonelective
      procedures completed at STH, complications, and mortality were comparable across
      centers.

PMID- 22583854
TI  - Comparative outcomes of primary autogenous fistulas in elderly, multiethnic Asian
      hemodialysis patients.
AB  - BACKGROUND: The number of elderly (>=65 years) end-stage renal disease (ESRD)
      patients on hemodialysis is rapidly increasing. Vascular access outcomes remain
      contradictory and understudied across different elderly populations. We
      hypothesized age might influence primary autogenous fistula use and outcomes in a
      predominantly diabetic multiethnic Asian ESRD population. METHODS: Demographic
      and clinical factors affecting fistula patency and maturation were
      retrospectively compared among patients with incident ESRD aged <65 and >=65
      years at a single center. Fistula patency was estimated by Kaplan-Meier curves
      with log-rank test comparison. RESULTS: We analyzed 280 primary fistulas (59%
      radiocephalic, 33% brachiocephalic, and 8% brachiobasilic) in this cohort
      consisting of 31.8% aged >=65 years, 50% Chinese, 39% Malay, 42% women, and 70%
      diabetic. One- and 2-year primary and secondary patency in patients aged <65 vs
      >=65 years were comparable: 41.3% vs 36.7% and 28.7% vs 24.4% (P = .547) and
      57.7% vs 56.8% and 47.1% vs 47.2% (P = .990). On multivariate analysis, only non
      Chinese, dialysis initiation with tunneled catheters, and surgical/endovascular
      interventions affected fistula survival hazard ratios (HR): 0.622 (95% confidence
      interval [CI], 0.43-1.00), 0.549 (95% CI, 0.297-0.841), and 2.503 (95% CI, 1.695
      3.697), respectively. Nonmaturation and intervention rates were also similar at
      56.7% vs 61.8% and 34% vs 32.2% at 3 and 6 months and 0.31 vs 0.36 per access
      year, respectively (P > .05). Females and tunneled catheters were the only risk
      factors for nonmaturation (HR, 1.568; 95% CI, 1.148-1.608, and HR, 1.623; 95% CI,
      1.400-1.881, respectively). CONCLUSIONS: A primary fistula strategy in incident
      elderly ESRD is feasible and does not result in inferior outcomes. Age should
      therefore not be a determinant for primary fistula creation.

PMID- 22583855
TI  - Lesional accumulation of CD163+ macrophages/microglia in rat traumatic brain
      injury.
AB  - A robust neuroinflammation, contributing to the development of secondary injury,
      is a common histopathological feature of traumatic brain injury (TBI).
      Characterization of leukocytic subpopulations contributing to the early
      infiltration of the damaged tissue might aid in further understanding of lesion
      development. Reactive macrophages/microglia can exert protective or damaging
      effects in TBI. CD163 is considered a marker of M2 (alternatively activated)
      macrophages. Therefore we investigated the accumulation of CD163(+)
      macrophages/microglia in the brain of TBI rats. TBI was induced in rats using an
      open skull weight-drop contusion model and the accumulation of CD163(+) cells was
      analyzed by immunohistochemistry. In normal rat brains, CD163 was expressed by
      meningeal, choroid plexus and perivascular macrophages. Significant parenchymal
      CD163(+) cell accumulation was observed two days post TBI and continuously
      increased in the investigated survival time. The accumulated CD163(+) cells were
      mainly distributed to the lesional areas and exhibited macrophage phenotypes with
      amoeboid morphologic characteristics but not activated microglial phenotypes with
      hypertrophic morphology and thick processes. Double-labeling experiments showed
      that most CD163(+) cells co-expressed heme oxygenase-1 (HO-1). In addition, in
      vitro incubating of macrophage RAW264.7 cells or primary peritoneal macrophages
      with hemoglobin- haptoglobin (Hb-Hp) complex suppressed LPS-induced inflammatory
      macrophages phenotype and induced CD163 and HO-1 upregulation, indicating that
      CD163(+) macrophages/microglia in TBI might have anti-inflammatory effects. And
      further study is necessary to identify functions of these cells in TBI.

PMID- 22583856
TI  - Neuroprotective effects of selective beta-1 adrenoceptor antagonists, landiolol
      and esmolol, on transient forebrain ischemia in rats; a dose-response study.
AB  - Although selective beta-1 adrenoceptor antagonists are known to provide
      neuroprotective effects after brain ischemia, dose-response relationships of
      their neuroprotective effects have not been examined. The present study was
      conducted to evaluate whether the degree of brain protection against transient
      forebrain ischemia would be influenced by different doses of selective beta-1
      adrenoceptor antagonists, esmolol and landiolol, in rats. Adult male S.D. rats
      received intravenous infusion of saline 0.5 ml/h, esmolol 20, 200, 2,000
      MUg/kg/min, or landiolol 5, 50, 500 MUg/kg/min. Infusion was initiated 30 min
      prior to ischemia and continued for 24h. Ten-minute forebrain ischemia was
      induced by hemorrhagic hypotension and occlusion of the bilateral carotid
      arteries. Neurological and histological examinations were performed. Neurological
      deficit scores at 1, 4 and 7 days were lower, and the number of intact neurons in
      CA1 hippocampal region was larger in the rats treated with esmolol and landiolol
      after ischemia, compared with saline-treated rats (P<0.05), whereas no difference
      was found among different doses of esmolol and landiolol. These results suggested
      that selective beta-1 adrenoceptor antagonists improved neurological and
      histological outcomes following forebrain ischemia in rats, irrespective of their
      doses.

PMID- 22583857
TI  - Analysis of intracranial pressure pulse waveform and brain capillary morphology
      in type 2 diabetes mellitus rats.
AB  - Diabetes mellitus in neurosurgical patients is known to be a disease with high
      risks and severe outcomes. However, the mechanism by which diabetes mellitus
      induces dysfunction of brain tissue is not well known. The hypothesis of this
      study was that the damage to brain microvasculature in diabetes mellitus results
      in impaired compliance of the brain. Pathological changes associated with type II
      diabetes were investigated using a rat model. Pathophysiological changes in
      diabetic brain tissue were also investigated to confirm cerebral compliance by
      analyzing intracranial pressure waveforms. Pathologic findings revealed
      thickening of the basement membrane and fibrous collagen infiltration into the
      inner basement membrane of the brain microvasculature in diabetes mellitus.
      Analysis of intracranial pressure waveforms revealed that the P2 portion
      increased in diabetic rats compared to the control and was increased further with
      the increase in intracranial pressure. Analysis of the differential pressure
      curve, with respect to time, demonstrated that intracranial elasticity showed a
      concomitant increase. Pathologic findings and intracranial pressure waveforms
      were consistent with changes in brain microvasculature in diabetes mellitus. The
      increase of elasticity of brain tissue in diabetes mellitus may exacerbate the
      damage of intracranial disease.

PMID- 22583858
TI  - Relationship between funding sources and outcomes of obesity-related research.
AB  - This study examined the relationship between funding sources and the outcomes of
      published obesity-related research. A list of funded projects for human nutrition
      research linking food intake to obesity in 2001-2005 was drawn from two distinct
      sources: (a) the federal government's semi-public generic commodity promotion or
      "checkoff" programs for Fluid Milk and Dairy and (b) the National Institutes of
      Health (NIH). The Principal Investigator for each funded project was determined.
      Published literature by that individual was located using an Ovid MEDLINE and
      PubMed author search. All articles related to both dairy and obesity were
      included. Financial sponsorship for each article and article conclusions were
      classified by independent groups of co-investigators. Seventy-nine relevant
      articles were included in the study. Of these, 62 were sponsored by the checkoff
      programs and 17 by the NIH. The study did not find consistent evidence that
      checkoff-funded projects were more likely to support an obesity prevention
      benefit from dairy consumption. The study did identify a new research methodology
      for the investigation of bias by source of sponsorship.

PMID- 22583859
TI  - Altered processing of sweet taste in the brain of diet soda drinkers.
AB  - Artificially sweetened beverage consumption has been linked to obesity, and it
      has been hypothesized that considerable exposure to nonnutritive sweeteners may
      be associated with impaired energy regulation. The reward system plays an
      integral role in modulating energy intake, but little is known about whether
      habitual use of artificial sweetener (i.e., diet soda consumption) may be related
      to altered reward processing of sweet taste in the brain. To investigate this, we
      examined fMRI response after a 12-hour fast to sucrose (a nutritive sweetener)
      and saccharin (a nonnutritive sweetener) during hedonic evaluation in young adult
      diet soda drinkers and non-diet soda drinkers. Diet soda drinkers demonstrated
      greater activation to sweet taste in the dopaminergic midbrain (including ventral
      tegmental area) and right amygdala. Saccharin elicited a greater response in the
      right orbitofrontal cortex (Brodmann Area 47) relative to sucrose in non-diet
      soda drinkers. There was no difference in fMRI response to the nutritive or
      nonnutritive sweetener for diet soda drinkers. Within the diet soda drinkers,
      fMRI activation of the right caudate head in response to saccharin was negatively
      associated with the amount of diet sodas consumed per week; individuals who
      consumed a greater number of diet sodas had reduced caudate head activation.
      These findings suggest that there are alterations in reward processing of sweet
      taste in individuals who regularly consume diet soda, and this is associated with
      the degree of consumption. These findings may provide some insight into the link
      between diet soda consumption and obesity.

PMID- 22583860
TI  - Post-weaning social isolation attenuates c-Fos expression in GABAergic
      interneurons in the basolateral amygdala of adult female rats.
AB  - Previous studies have found that adolescent social isolation of rats can lead to
      an increased anxiety state during adulthood, while chronic anxiety states are
      associated with dysregulated local GABAergic inhibition within the basolateral
      amygdala (BL). Therefore, we investigated the effects of post-weaning social
      isolation of female rats, in combination with a challenge with the anxiogenic
      drug, N-methyl-beta-carboline-3-carboxamide (FG-7142), on a subset of GABAergic
      interneurons in the BL in adulthood using dual immunohistochemical staining for c
      Fos and parvalbumin. Juvenile female rats were reared in isolation or in groups
      of three for a 3-week period from weaning to mid-adolescence, after which all
      rats were group-housed for an additional 2 weeks. Group-reared rats and isolation
      reared rats injected with FG-7142 had increased c-Fos expression in GABAergic
      interneurons in the anterior part of the BL compared to group-reared rats and
      isolation-reared rats, respectively, injected with vehicle. Isolation rearing had
      a main effect to decrease c-Fos expression in GABAergic interneurons in the
      anterior part of the BL compared to group-reared rats. These data suggest that
      post-weaning social isolation of female rats leads to dysregulation of a
      parvalbumin-containing subset of local GABAergic interneurons in the anterior
      part of the BL, which have previously been implicated in the pathophysiology of
      chronic anxiety states. These cellular changes may lead to an increased
      vulnerability to stress- and anxiety-related responses in adulthood.

PMID- 22583862
TI  - Effects of testosterone administration and gonadectomy on incentive downshift and
      open field activity in rats.
AB  - Previous research showed that the effects of incentive downshift in male rats are
      attenuated by a pretrial opportunity to ejaculate. Because ejaculation raises
      testosterone (T) levels and has anxiolytic-like effects in male rats, the present
      experiments were designed to assess the role of T and gonadectomy (GDX) on two
      situations involving incentive downshift. In consummatory successive negative
      contrast, a downshift from 32% to 4% sucrose leads to consummatory suppression. T
      alleviates such suppression (Experiment 1), but GDX does not affect it
      (Experiment 3). In consummatory extinction, animals are downshifted from 32%
      sucrose to an empty sipper tube. T enhances consummatory extinction (Experiment
      2), but GDX does not affect it (Experiment 4). In agreement with published
      results, T increases (Experiment 2) and GDX reduces (Experiment 4) activity in
      the central area of an open field, thus behaviorally validating these
      manipulations. The results are discussed in terms of the anxiolytic-like
      properties of androgen hormones.

PMID- 22583863
TI  - Youth in the Netherlands study (JOiN): study design.
AB  - BACKGROUND: Adolescence is a critical developmental period regarding exposure to
      substances. Therefore, it is important to be able to identify those adolescents
      who are most vulnerable to substance abuse in the (near) future. The JOiN study
      was specifically designed to examine two endophenotypes of adolescent substance
      use in a normal risk (NR) and high risk (HR) sample of adolescents: (1)
      behavioural disinhibition, and (2) individual differences in stress sensitivity.
      METHODS: The NR adolescents were part of a longitudinal general population study
      at the Erasmus Medical Center in Rotterdam, the Netherlands of children and
      adolescents initially aged 6 to 18 years old. Three assessment waves have been
      nearly completed, and data are available of N = 711 participants for stress
      sensitivity measures, and of a subsample of N = 110 for electroencephalography
      (EEG) measures. Added to this study, HR adolescents who had at least one parent
      with a substance use disorder and who were treated by an outpatient clinic of a
      primary addiction care provider were approached via their parent(s). In total, N
      = 83 adolescents formed this HR sample. NR and HR adolescents participated in
      standardized stress procedure and EEG procedures in our laboratory.
      Questionnaires were filled out on background variables, behavioural and emotional
      problems, and substance use, and a diagnostic interview was conducted with
      adolescents and parents to assess psychopathology symptoms. DNA was collected
      through saliva or blood samples. DISCUSSION: The design of the JOiN study is
      optimal for examining the predictive role of endophenotypes of adolescent
      substance use. The combination of different methods, i.e. stress physiology,
      electrophysiology, genetics, and questionnaire data from several informants on a
      range of behaviours and environmental factors enables the investigation of the
      multifactorial nature of adolescent substance use.

PMID- 22583861
TI  - Rationale and consequences of reclassifying obesity as an addictive disorder:
      neurobiology, food environment and social policy perspectives.
AB  - The rapid increase in the prevalence of obesity is a priority for investigators
      from across numerous disciplines, including biology, nutritional science, and
      public health and policy. In this paper, we systematically examine the premise
      that common dietary obesity is an addictive disorder, based on the criteria for
      addiction described in the Diagnostic and Statistical Manual (DSM) of Mental
      Disorders of the American Psychiatric Association, version IV, and consider the
      consequences of such a reclassification of obesity for public policy.
      Specifically, we discuss evidence from both human and animal studies
      investigating the effects of various types and amounts of food and the food
      environment in obese individuals. Neurobiological studies have shown that the
      hedonic brain pathways activated by palatable food overlap considerably with
      those activated by drugs of abuse and suffer significant deficits after chronic
      exposure to high-energy diets. Furthermore, food as a stimulus can induce the
      sensitization, compulsion and relapse patterns observed in individuals who are
      addicted to illicit drugs. The current food environment encourages these
      addictive-like behaviors where increased exposure through advertisements,
      proximity and increased portion sizes are routine. Taking lessons from the
      tobacco experience, it is clear that reclassifying common dietary obesity as an
      addictive disorder would necessitate policy changes (e.g., regulatory efforts,
      economic strategies, and educational approaches). These policies could be
      instrumental in addressing the obesity epidemic, by encouraging the food industry
      and the political leadership to collaborate with the scientific and medical
      community in establishing new and more effective therapeutic approaches.

PMID- 22583864
TI  - Genome-scale modeling using flux ratio constraints to enable metabolic
      engineering of clostridial metabolism in silico.
AB  - BACKGROUND: Genome-scale metabolic networks and flux models are an effective
      platform for linking an organism genotype to its phenotype. However, few modeling
      approaches offer predictive capabilities to evaluate potential metabolic
      engineering strategies in silico. RESULTS: A new method called "flux balance
      analysis with flux ratios (FBrAtio)" was developed in this research and applied
      to a new genome-scale model of Clostridium acetobutylicum ATCC 824 (iCAC490) that
      contains 707 metabolites and 794 reactions. FBrAtio was used to model wild-type
      metabolism and metabolically engineered strains of C. acetobutylicum where only
      flux ratio constraints and thermodynamic reversibility of reactions were
      required. The FBrAtio approach allowed solutions to be found through standard
      linear programming. Five flux ratio constraints were required to achieve a
      qualitative picture of wild-type metabolism for C. acetobutylicum for the
      production of: (i) acetate, (ii) lactate, (iii) butyrate, (iv) acetone, (v)
      butanol, (vi) ethanol, (vii) CO2 and (viii) H2. Results of this simulation study
      coincide with published experimental results and show the knockdown of the
      acetoacetyl-CoA transferase increases butanol to acetone selectivity, while the
      simultaneous over-expression of the aldehyde/alcohol dehydrogenase greatly
      increases ethanol production. CONCLUSIONS: FBrAtio is a promising new method for
      constraining genome-scale models using internal flux ratios. The method was
      effective for modeling wild-type and engineered strains of C. acetobutylicum.

PMID- 22583865
TI  - Genetic and genome-wide transcriptomic analyses identify co-regulation of
      oxidative response and hormone transcript abundance with vitamin C content in
      tomato fruit.
AB  - BACKGROUND: L-ascorbic acid (AsA; vitamin C) is essential for all living plants
      where it functions as the main hydrosoluble antioxidant. It has diverse roles in
      the regulation of plant cell growth and expansion, photosynthesis, and hormone
      regulated processes. AsA is also an essential component of the human diet, being
      tomato fruit one of the main sources of this vitamin. To identify genes
      responsible for AsA content in tomato fruit, transcriptomic studies followed by
      clustering analysis were applied to two groups of fruits with contrasting AsA
      content. These fruits were identified after AsA profiling of an F8 Recombinant
      Inbred Line (RIL) population generated from a cross between the domesticated
      species Solanum lycopersicum and the wild relative Solanum pimpinellifollium.
      RESULTS: We found large variability in AsA content within the RIL population with
      individual RILs with up to 4-fold difference in AsA content. Transcriptomic
      analysis identified genes whose expression correlated either positively (PVC
      genes) or negatively (NVC genes) with the AsA content of the fruits. Cluster
      analysis using SOTA allowed the identification of subsets of co-regulated genes
      mainly involved in hormones signaling, such as ethylene, ABA, gibberellin and
      auxin, rather than any of the known AsA biosynthetic genes. Data mining of the
      corresponding PVC and NVC orthologs in Arabidopis databases identified flagellin
      and other ROS-producing processes as cues resulting in differential regulation of
      a high percentage of the genes from both groups of co-regulated genes; more
      specifically, 26.6% of the orthologous PVC genes, and 15.5% of the orthologous
      NVC genes were induced and repressed, respectively, under flagellin22 treatment
      in Arabidopsis thaliana. CONCLUSION: Results here reported indicate that the
      content of AsA in red tomato fruit from our selected RILs are not correlated with
      the expression of genes involved in its biosynthesis. On the contrary, the data
      presented here supports that AsA content in tomato fruit co-regulates with genes
      involved in hormone signaling and they are dependent on the oxidative status of
      the fruit.

PMID- 22583866
TI  - Acute presentation of a plunging ranula causing respiratory distress: case
      report.
AB  - OBJECTIVE: A plunging ranula is an uncommon cause of neck swelling which
      typically presents in a gradually progressive fashion. This report describes a
      rare case of acute presentation of a plunging ranula. The condition progressed
      rapidly to respiratory distress, requiring urgent surgery. CASE REPORT: A 14-year
      old male student presented with a rapidly enlarging neck swelling associated with
      a sublingual swelling. Computed tomography suggested the diagnosis of plunging
      ranula. Several hours after admission, the neck swelling became very tense and
      the sublingual swelling enlarged dramatically. The tongue was pushed upwards and
      backwards by the sublingual swelling, causing respiratory embarrassment and
      requiring urgent surgery. Four months after surgery, there was no evidence of
      recurrence. CONCLUSION: To the best of the author's knowledge, this is the first
      case report of a plunging ranula progressing acutely and rapidly to cause
      respiratory compromise. The literature is reviewed and pertinent features
      concerning the diagnosis and management of plunging ranula are presented.

PMID- 22583867
TI  - T cell independent secondary antibody responses to the envelope protein of simian
      immunodeficiency virus.
AB  - BACKGROUND: During human (HIV) and simian (SIV) immunodeficiency virus infection,
      loss of CD4+ T cells and progression to AIDS are associated with a decline in
      antibody titers to the viral Gag protein, while antibodies to the Env protein
      remain high, suggesting a T cell independent antibody response to Env. RESULTS:
      To explore differential regulation of Gag and Env antibody responses,
      immunocompetent BALB/c and T cell deficient nude mice were immunized with virus
      like particles (VLP) of simian immunodeficiency virus or adenoviral vectors
      expressing SIV Gag and Env. High levels of antibodies against Gag and Env could
      only be induced in immunocompetent mice, but not in the immunodeficient mice.
      Thus, neither cells expressing Env after adenoviral gene transfer nor VLPs induce
      a T cell independent primary anti-Env antibody response. However, secondary B
      cell responses to Env, but not to Gag, were observed in immunodeficient mice
      after transfer of primed B cells and boosting with VLPs or adenoviral vectors
      expressing Gag and Env. This T cell independent secondary antibody response to
      Env was reduced after stimulation with VLPs modified to contain monomeric
      membrane bound gp130 surface subunit of Env and undetectable after injection of
      soluble gp130. CONCLUSIONS: Membrane-bound trimeric Env seems to be responsible
      for the maintenance of high levels of anti-Env antibodies during progression to
      AIDS. This T cell independent secondary antibody response may prevent T cell
      dependent affinity maturation and thus contribute to viral immune escape by
      favoring persistence of non-protective antibodies.

PMID- 22583868
TI  - Protective effect of the poly(ADP-ribose) polymerase inhibitor PJ34 on
      mitochondrial depolarization-mediated cell death in hepatocellular carcinoma
      cells involves attenuation of c-Jun N-terminal kinase-2 and protein kinase B/Akt
      activation.
AB  - BACKGROUND: 2,4-Dimethoxyphenyl-E-4-arylidene-3-isochromanone (IK11) was
      previously described to induce apoptotic death of A431 tumor cells. In this
      report, we investigated the molecular action of IK11 in the HepG2 human
      hepatocellular carcinoma cell line to increase our knowledge of the role of poly
      (ADP-ribose)-polymerase (PARP), protein kinase B/Akt and mitogen activated
      protein kinase (MAPK) activation in the survival and death of tumor cells and to
      highlight the possible role of PARP-inhibitors in co-treatments with different
      cytotoxic agents in cancer therapy. RESULTS: We found that sublethal
      concentrations of IK11 prevented proliferation, migration and entry of the cells
      into their G2 phase. At higher concentrations, IK11 induced reactive oxygen
      species (ROS) production, mitochondrial membrane depolarization, activation of c
      Jun N-terminal kinase 2 (JNK2), and substantial loss of HepG2 cells. ROS
      production appeared marginal in mediating the cytotoxicity of IK11 since N-acetyl
      cysteine was unable to prevent it. However, the PARP inhibitor PJ34, although not
      a ROS scavenger, strongly inhibited both IK11-induced ROS production and cell
      death. JNK2 activation seemed to be a major mediator of the effect of IK11 since
      inhibition of JNK resulted in a substantial cytoprotection while inhibitors of
      the other kinases failed to do so. Inhibition of Akt slightly diminished the
      effect of IK11, while the JNK and Akt inhibitor and ROS scavenger trans
      resveratrol completely protected against it. CONCLUSIONS: These results indicate
      significant involvement of PARP, a marginal role of ROS and a pro-apoptotic role
      of Akt in this system, and raise attention to a novel mechanism that should be
      considered when cancer therapy is augmented with PARP-inhibition, namely the
      cytoprotection by inhibition of JNK2.

PMID- 22583869
TI  - A highly conserved tryptophan in the N-terminal variable domain regulates
      disulfide bond formation and oligomeric assembly of adiponectin.
AB  - Adiponectin is a collagenous adipokine with direct anti-diabetic and anti
      atherogenic properties. It can assume an ensemble of oligomeric states, e.g.
      trimers, hexamers and octadecamers, each being involved in distinct signaling
      pathways relevant to adiponectin's diverse biological function in metabolism,
      immunity, inflammation and cellular homeostasis. Assembly of the active variants
      principally the octadecameric high molecular weight form is achieved via the
      tightly controlled oxidation of cysteine 39 located in the adiponectin hyper
      variable domain (AHD, residues 18-44) between the signal sequence and the
      collagen-like domain. We show that mutation of a highly conserved tryptophan
      (W42A) in the AHD profoundly affects assembly by trapping full-length adiponectin
      in the oxidized trimeric or hexameric states with a concomitant major reduction
      in the high molecular weight form. Our biophysical measurements on synthesized
      analogues of the AHD suggests that the aberrant oligomer distribution can be
      explained based on the fact that the proximity of W42 to C39 causes a reduction
      in the rate of C39 oxidation, an effect that to our knowledge has not been
      documented before. At the biological level, the perturbed oligomer distribution
      of full-length mutant adiponectin leads to a major reduction in the AMP-activated
      protein kinase activation in endothelial cells and liver tissues.

PMID- 22583870
TI  - Children with severe early childhood caries: pilot study examining mutans
      streptococci genotypic strains after full-mouth caries restorative therapy.
AB  - PURPOSE: Genotypic strains of mutans streptococci (MS) may vary in important
      virulence properties and be differentially affected by specific components of
      full-mouth caries restorative therapy. The purpose of this pilot study was to
      identify mutans streptococci strains that predominate  following caries
      restorative therapy. METHODS: Plaque from 7 children with severe early childhood
      caries was collected before and following therapy. MS isolates (N=828) were
      subjected to polymerase chain reaction (PCR) and arbitrarily primed-PCR (AP-PCR)
      for assignment within MS strains.  Determining the longitudinal changes in MS
      strain distribution over time within each patient required the isolation of
      larger numbers of isolates per patient, but from fewer patients. RESULTS: Up to
      39 genotypic strains of Streptococcus mutans and Streptococcus sobrinus, and 7
      genotypic  strains of non-MS streptococci were identified by AP-PCR and 16S
      ribosomal rRNA gene sequencing. The number of MS strains isolated from each
      patient were 3 to 7 prior to treatment, diminishing to 1 to 2 dominant MS strains
      in most patients 6 months following therapy. CONCLUSIONS: Caries  restorative
      therapy resulted in shifts of specific mutans streptococcus and non-mutans
      streptococcus strains. The implications are that caries restorative therapy
      affects the distribution of MS strains, and that well-accepted practices for
      caries prevention should be more closely examined  for efficacy.

PMID- 22583871
TI  - Effect of different concentrations of chlorhexidine on bond strength of primary
      dentin.
AB  - PURPOSE: The purpose of this study was to assess the effect of different
      concentrations of chlorhexidine digluconate on the bond strength to primary tooth
      dentin immediately and after 12 months. METHODS: Twenty-one sound primary molars
      were assigned to 3 groups (N=7). The bonding procedure  was performed in control
      group (A) using 37% phosphoric acid gel (15 seconds), then washed (15 seconds),
      dried with air (30 seconds), and rehydrated with water. Groups B and C had the
      rewetting procedure performed, respectively, with 0.5% and 2% chlorhexidine for
      30 seconds. The tensile bond  strength was tested immediately (IM) or after
      storage in artificial saliva for 12 months (12M). Data were evaluated by 2-way
      repeated measures analysis of variance and Tukey's post-hoc test. RESULTS: There
      was no significant reduction in bond strength values when chlorhexidine was used
      at  concentrations of 0.5% (IM=49.3/2.6 and 12M=32.3/7.9) and 2% (IM=44.0/8.7 and
      12M=34.6/5.1). Conversely, a significantreduction in bond strength was observed
      in the control group (IM=50.8/12.8 and 12M=20.4/3.7). CONCLUSION: The study
      validates the concept that chlorhexidinesolution, at different  concentrations,
      may prevent the degradation of the adhesive interface in primary teeth.

PMID- 22583873
TI  - Vertical transmission of mutans streptococci and lactobacillus in Thai families.
AB  - PURPOSE: The purpose of this study was to investigate the vertical transmission
      of mutans streptococci (MS) and lactobacilli in a group of Thai families.
      METHODS: One hundred eighty-one mother-child pairs were included in this study.
      Unstimulated saliva was collected using  the spatula method and counted for
      evaluating the number of MS and lactobacilli on a selective medium. Genotyping of
      MS and Lactobacillus species were performed in 37 and 22 child-mother pairs,
      respectively. Typically, 3 to 4 isolates of MS and/or Lactobacillus strains from
      each mother and  child were collected for genotyping by an arbitrarily primed
      polymerase chain reaction (OPA-02 primer for MS and enterobacterial repetivive
      intergenic consensus primers for Lactobacillus species). RESULTS: Generally, MS
      and lactobacilli levels in children were associated with their  mothers' levels.
      Genotyping of most isolates of MS and Lactobacillus strains in both mothers and
      children found diversity, and each individual showed a distinct genotypic
      pattern. The presence of matching genotypes of MS and Lactobacillus strains of
      mother-child was approximately 76% and 50%,  respectively. The genotypes acquired
      from the maternal route show effective persistence in the children's oral
      cavities. CONCLUSIONS: In Thai families, mothers can be the source for
      transmission of mutans streptococci and Lactobacillus strains to their children.

PMID- 22583872
TI  - Aciduric microbiota and mutans streptococci in severe and recurrent severe early
      childhood caries.
AB  - PURPOSE: Severe early childhood caries (ECC) results from bacterial acid
      production in an acidic environment. The purpose of this study was to determine
      Streptococcus mutans, Streptococcus sobrinus, and acid-tolerant counts in severe
      early childhood caries. METHODS: Two-  to 6-year-olds with severe-ECC (N=77) or
      who were caries-free (N=40) were examined. Plaque samples from teeth and the
      tongue were cultured anaerobically on blood, acid, and S. mutans selective agars.
      Severe-ECC children were monitored post-treatment for recurrent caries. RESULTS:
      Severe-ECC  and caries-free children were balanced by household income and
      education level. Carious lesions were observed in 75% maxillary incisors and >80%
      molars in severe-ECC. At baseline, S. mutans, and S. sobrinus counts and
      proportions of S mutans were higher in severe-ECC than caries-free children. 
      Acid and blood counts were elevated only in anterior samples of severe-ECC
      children. Baseline counts of S. sobrinus, but not S. mutans, were higher in
      children with recurrent compared with no recurrent caries. S. mutans counts were
      lower following treatment than pretreatment, particularly  for children without
      caries recurrence. Other counts did not differ between before and after therapy.
      CONCLUSIONS: Severe and recurrent early childhood caries was better explained by
      mutans streptococci than the aciduric microbiota. Streptococcus mutans did not
      predict children with  recurrent caries.

PMID- 22583874
TI  - Association among stress, personality traits, and sleep bruxism in children.
AB  - PURPOSE: The purpose of this study was to determine the association among stress
      levels, personality traits, and sleep bruxism in children. METHODS: A population
      based case control study (proportion=1:2) was conducted involving 120 7- to 11
      year-olds with sleep bruxism and 240 children without sleep bruxism. The sample
      was randomly selected from schools in Belo Horizonte, Minas Gerais, Brazil. The
      following instruments were used for data collection: questionnaire administered
      to parents; child stress scale; and neuroticism and responsibility scales of the
      big five questionnaire for children. Psychological tests were administered and
      evaluated by psychologists. Sleep bruxism was diagnosed from parents' reports.
      The chi-square test, as well as binary and multivariate logistic regression, was
      applied for statistical analysis. RESULTS: In the adjusted logistic model,
      children with a high level of stress, due to psychological reactions (odds
      ratio=1.8; confidence interval=1.1-2.9) and a high sense of responsibility
      (OR=1.6; CI=1.0-2.5) vs those with low levels of these psychological traits,
      presented a nearly 2-fold greater chance of exhibiting the habit of sleep
      bruxism. CONCLUSION: High levels of stress and responsibility are key factors in
      the development of sleep bruxism among children.

PMID- 22583875
TI  - Effectiveness of new distraction technique on pain associated with injection of
      local anesthesia for children.
AB  - PURPOSE: Distraction is one of the most commonly used techniques for control of
      pain associated with injection procedures. This study's purpose was to evaluate
      the effect of a distraction technique using audiovisual (A/V) glasses on pain
      perception during administration of local  anesthesia for children. METHODS:
      Forty-eight healthy, cooperative 5- to 7-year-olds were selected on the basis of
      existence of bilateral carious primary mandibular molars, which necessitated an
      inferior alveolar nerve block anesthesia before treatment. Treatment was done on
      2 visits  1 week apart. Children had been randomly assigned to receive the A/V
      glasses at one visit and no distraction during the other visit. Two different
      pain assessment scales were used: the pain faces scale (PFS) and the face, legs,
      activity, cry, and consolability scale (FLACC) scale. Kappa statistics  were
      calculated for the reliability of the observer when using the FLACC scale. A
      comparison between the 2 study techniques was done using the Wilcoxon signed
      ranks test. RESULTS: Kappa values ranged from 0.89 to 1.00. The pain scores in
      both scales were significantly lower when the  A/V glasses were used. CONCLUSION:
      Distraction induced by audiovisual glasses was an effective way to reduce the
      pain associated with injection of local anesthesia.

PMID- 22583876
TI  - A case of Klippel-Feil and Turner syndromes.
AB  - The purpose of this paper was to describe the clinical case of a 12-year-old
      female patient with Klippel-Feil syndrome (KFS) combined with Turner syndrome
      (TS) and a submucous cleft palate (CP). The patient's general appearance was
      characterized by KFS, a clinical triad consisting of congenital fusion of at
      least 2 of 7 cervical vertebrae with a short neck, limited head motion, and a low
      posterior hairline. Three-dimensional images from cone-beam computed tomography
      (CBCT) revealed cervical vertebrae anomalies and submucous CP. It was reported
      that the patient had TS and has been administered growth hormone (GH) therapy.
      Due to a skeletal class III pattern with a steep mandibular plane angle, facial
      asymmetry, and fused cervical vertebrae, GH's effects on the craniofacial complex
      should be considered before orthopedic/orthodontic treatment is started.

PMID- 22583877
TI  - Orthodontic treatment of transposition of permanent mandibular lateral incisor
      and left canine in mixed dentition: a case report.
AB  - The purpose of this study was to present the orthodontic treatment of a
      unilateral transposition of a permanent mandibular left canine and permanent
      mandibular lateral incisor during middle transitional dentition in a 10-year-old
      female. A panoramic radiograph showed the apex of the permanent mandibular left
      lateral incisor to be resting on the mesial corner of the permanent mandibular
      left canine crown, which was ectopically erupted in the proximity of the primary
      mandibular left second molar. A removable appliance was used to upright the
      permanent mandibular left lateral incisor, after which a utility arch was used
      until full eruption of the permanent dentition. Treatment continued with a fixed
      appliance system that included all teeth until the transposition of the canine
      and lateral incisor was corrected and a class I occlusion with a favorable smile
      was obtained (at 36 months).

PMID- 22583879
TI  - Success of Hall technique crowns questioned.
AB  - Hall technique is a method of providing stainless steel crowns for primary molars
      without tooth preparation and requires no local anesthesia. Literature review
      showed inconclusive evidence and therefore this technique should not be used in
      clinical practice.

PMID- 22583880
TI  - Dental trauma occurrence and occlusal characteristics in Brazilian preschool
      children.
AB  - PURPOSE: The purpose of this study was to analyze the association between dental
      trauma and occlusal traits in the primary dentition. METHODS: Five hundred and
      one 24- to 71-month-old children, attending both private and public schools in
      Pelotas, Rio Grande do Sul, Brazil,  were included. Clinical examinations were
      performed at each school. Occurrence of dental trauma was assessed using the
      Andreasen and Andreasen classification. Occlusal characteristics used in this
      study were: overjet; open bite; overbite; anterior crossbite; crowding and
      rotated teeth occurrence;  and canine class. The occlusion type was classified
      according to the World Health Organization. A questionnaire was sent to parents
      to obtain socioeconomic data. Descriptive statistics were used, as well as chi
      square tests (for heterogeneity or linear trend; P <= .05) and Fisher's exact 
      test. RESULTS: The prevalence of dental trauma was 40% (95% confidence
      interval=35-44). Of all children examined, 20% showed normal occlusion, 42% mild
      malocclusion, and 38% moderate/severe malocclusion. Dental trauma was associated
      with overjet >= 3 mm (P=.02), overbite >= 3 mm  (P=.01), and canine class
      (P=.04). Children bearing mild or moderate/severe malocclusion presented greater
      dental trauma (P<.01). CONCLUSION: The findings of this study emphasize the
      importance of preventing dental trauma, especially in children presenting
      increased overjet, overbite,  or canine Class II.

PMID- 22583882
TI  - Radiographic study of prevalence and distribution of hypodontia in a pediatric
      orthodontic population in Venezuela.
AB  - PURPOSE: This study's purpose was to determine prevalence and distribution of
      hypodontia in a pediatric orthodontic population in Caracas, Venezuela. METHODS:
      A total of 607 dental records (radiographs, cast models, and photographs) from 5-
      to 11-year-old patients of an interceptive orthodontics clinic were studied for
      agenesis of permanent teeth. Patients with hypodontia of the third molars and
      syndromes of cleft lip or palate were excluded. Data were analyzed using t tests
      (=.05) and Pearson's chi-square (P=.001). RESULTS: Hypodontia affected 25
      patients (~4%): 13 with unique and 12 with multiple tooth agenesis. Females were
      more affected than males (1.5:1). A total of 40 teeth were missing: permanent
      maxillary lateral incisors (40%); mandibular second premolars (~23%); maxillary
      second premolars (15%); permanent mandibular lateral incisors (15%); and
      permanent mandibular second molars (~8%). The maxilla was more affected (55%) vs.
      the mandible (45%). Symmetrical hypodontia was exhibited by the maxilla, whereas
      the left premolar region was most affected in the mandible. CONCLUSION: The most
      affected tooth was the permanent maxillary lateral incisor, followed by the
      mandibular second premolar; symmetry was noted for hypodontia in the maxilla, and
      an inverse correlation was found between the maxillary and mandibular hypo-
      dontia. The overall results agree with other Latin American studies and differ
      from Caucasian or Asian populations.

PMID- 22583881
TI  - The effect of adenoidectomy or adenotonsillectomy on occlusal features in mouth
      breathing preschoolers.
AB  - PURPOSE: The purpose of this study was to evaluate mouth-breathing and nasal
      breathing children prior to surgical intervention and 28 months postoperatively,
      comparing the occlusal features obtained pre- and postoperatively through
      orthodontic study casts. METHODS: The  mouth-breathing (MB) group consists of 33
      MB children who underwent surgery and presented a nasal-breathing (NB) pattern
      after surgery. The control group comprised 22 NB children. The orthodontic
      examinations were accomplished prior to surgery (T1) and an average of 28 months
      postoperatively  (T2). RESULTS: At T1, the MB and NB children presented no
      statistically significant difference in any analyzed occlusal features and
      measurements. At T2, the MB presented larger overjet comparing to NB children
      (P<.05). MB and NB groups presented statistically similar results (P>.05) 
      concerning intercanine and intermolar distances, second primary molar terminal
      plane and canine relationship, overbite, crossbite, and open bite. From T1 to T2,
      the MB and NB groups showed a statistically significant difference in the molar
      terminal plane. CONCLUSION: Neither the breathing  pattern nor the surgery had
      any effect on occlusal features in 3- to 6- year-olds.

PMID- 22583883
TI  - A longitudinal study of the association between breast-feeding and harmful oral
      habits.
AB  - PURPOSE: The purpose of this paper was to study the pattern of breast-feeding and
      harmful sucking habits (pacifier- and thumb-sucking) from birth to 12-months-old.
      METHODS: A prospective cohort study with 80 newborn infants and their mothers was
      conducted. A semi-structured  questionnaire on breast-feeding and pacifier- and
      thumb-sucking behavior was administered during monthly household visits. Data
      were analyzed using the chi-square test. RESULTS: Exclusive breast-feeding
      occurred in 50% of infants from birth while 69% of participants were completely 
      weaned by 12-months-old. Pacifier-sucking was more prevalent than thumb-sucking
      and was maintained at a higher rate than thumb-sucking throughout the study. The
      incidence of thumb-sucking was highest between the third and sixth month of life.
      There was a significant association between a low  rate of breast-feeding and
      pacifier-sucking at the 12-month visit (chi-square=5.29; P<.05). Thumb-sucking
      did not significantly correlate with breast-feeding behavior. CONCLUSION: The
      rate of exclusive breast-feeding was lower than that recommended by the World
      Health Organization.  More than half the infants had a pacifier- and / or thumb
      sucking habit during the study, and the incidence of breast-feeding was lower in
      those who used a pacifier.

PMID- 22583884
TI  - Assessment of diffusion of hydroxyl and calcium ions of root canal filling
      materials in primary teeth.
AB  - PURPOSE: The purpose of this study was to evaluate the diffusion of hydroxyl (OH
      ) and calcium (Ca+2) of 2 intracanal calcium hydroxide-based medications through
      the root dentin and cementum of primary teeth. METHODS: Forty roots were selected
      and a single operator instrumented the canals. The irrigation was performed with
      a 1% sodium hypochlorite solution, and a final irrigation used 17%
      ethylenediaminetetraacetic acid solution. The teeth were divided into 3 groups:
      (1) group 1 (N=15)- thickened calcium hydroxide paste blended with propylene
      glycol paste; (2) group 2 (N=15)-Calen; and (3) group 3 (N=10)-no medication.
      Diffusion of the OH-ions was determined using a digital pH meter, and diffusion
      of Ca+2 ions was determined through atomic absorption spectrometry at baseline,
      24 hours, 7 days, 15 days, and 30 days later. RESULTS: Two-way analysis of
      variance and Tukey's test revealed that Group 1 achieved significantly higher pH
      values (P<.01), followed by Groups 2 and 3. There was a statistically significant
      difference between groups (P<.01) in the amount of Ca+2 ions released; group 1
      had the highest diffusion values, followed by group 2, both with peak diffusion
      at 7 days. CONCLUSIONS: Thickened calcium hydroxide paste blended with propylene
      glycol paste achieved the greatest diffusion of hydroxyl and calcium through the
      dentin and cementum of primary teeth.

PMID- 22583885
TI  - Caries experience in individuals with cleft lip and palate.
AB  - PURPOSE: The purpose of this study was to assess if children with clefts have an
      increased caries experience. METHODS: Caries data was collected via clinical
      examination of 115 4- to 21-year-olds with clefts and 230 controls. Cleft type
      was confirmed through their medical  records and fluoride exposure history; oral
      hygiene habits and dietary history were obtained though a questionnaire. RESULTS:
      The adherence to the preventive oral health habits (tooth-brushing, use of
      fluoride, and dietary factors) were not different among groups excluding the use
      of  dental floss. The mean DMFT was 1.20 (+/-1.8 SD) for the cleft group and 0.90
      (+/-1.8) for the control group. There was no significant difference in the DMFT
      scores between children with clefts and the control group (P=.16). The mean dmft
      was 1.68 (+/-2.1) for the cleft group  and 2.61 (+/-2.9) for the control group.
      The prevalence of dental caries in primary teeth was significantly lower in the
      cleft-affected children vs the control group (P=.02). The percentage of caries
      free individuals was similar in cleft and control groups (P=.90), and was also
      similar  in different cleft types (P=.67). CONCLUSION: Caries experience in
      children born with clefts is not higher in comparison to control children.

PMID- 22583886
TI  - Conscious sedation attitudes and perceptions: a survey of american academy of
      pediatric dentistry members.
AB  - PURPOSE: The purpose of this study was to assess the attitudes and perceptions of
      the American Academy of Pediatric Dentistry (AAPDM) members regarding conscious
      sedation. METHODS: A 22-item survey was e-mailed to 4,358 active AAPD members to
      identify factors that  influence pediatric dentists' practice of conscious
      sedation in their dental offices. Bivariate and logistic regression models were
      used to analyze data. RESULTS: A total of 1,219 surveys were returned (28%
      response rate); 743 (63%) respondents practiced conscious sedation. Help in 
      providing dental care for patients difficult to manage was the primary reason
      reported for practicing conscious sedation. Conversely, not wanting the liability
      related to conscious sedation was the main reason reported by those who don't
      sedate. Bivariate and multivariate logistic regression  analyses indicated that
      dentists were significantly more likely to perform conscious sedation if they
      practiced more than 3 days a week (P>.03), had 11% or more patients with public
      insurance (P>.02), and rated their sedation training as "good or excellent"
      (P<.001). CONCLUSIONS: Among respondents, the attitudes of those who practice
      conscious sedation varied significantly from those who don't with location of the
      practice and the quality of their sedation training as significant influences on
      this decision.

PMID- 22583887
TI  - Oral intubation in premature infants with and without stabilizing devices.
AB  - PURPOSE: This study evaluated the effects of palatal stabilizing devices (PSDs)
      on accidental extubations (AEs) and other intubation complications in infants
      with breathing tubes at a neonatal intensive care unit (NICU) of a university
      hospital. PSDs are individually crafted  acrylic oral devices for stabilizing
      breathing tubes in neonates. METHODS: Charts of all first admission NICU neonates
      weighing less than 1,500 g were reviewed (N =733); 548 were intubated and had
      information available on birth weight, gender, transfer status, gestational age,
      length  of admission, ventilator type, sedation, dates of intubations and
      extubations, number of accidental extubations, dates of PSD placement, and
      complications. RESULTS: 153 subjects received PSDs, with 19 AEs; 395 received no
      PSDs, with 31 AEs. Non-PSD neonates were intubated for a median  of 3 and PSD
      neonates for 26 days. PSDs were associated with sedation, male gender, longer
      admissions, longer intubation periods, being on a high-frequency ventilator, and
      low birth weight (P<.05). 0.4 accidental extubations over 100 intubated patient
      days were recorded for the PSD vs 0.79  for the non-PSD group. CONCLUSIONS:
      Palatal stabilizing devices were not related to other complications of breathing
      tubes. The PSD group had fewer accidental extubations per days of intubation vs
      the non-PSD group.

PMID- 22583888
TI  - Overdenture for total rehabilitation in a child with early childhood caries.
AB  - The purpose of this case report was to present a clinical case of overdenture in
      a 3-year-old patient with early loss of his primary maxillary teeth, which were
      extracted due to the presence of early childhood caries. The treatment of choice
      was an overdenture using the Dalla Bona retention  system, and the upper right
      canine was used as the retainer. The overdenture was placed to help maintain a
      normal daily diet that was satisfactory for the child and to re-establish
      masticatory function, speech, and facial aesthetics in the patient.

PMID- 22583889
TI  - Solitary median maxillary central incisor: a report of 2 cases.
AB  - A single median maxillary central incisor (SMMCI) is a rare dental anomaly that
      may occur alone or be associated with growth deficiency or other systemic
      abnormalities. The best known association is with holoprosencephaly (HPE). HPE is
      a complex brain malformation that affects both  the forebrain and the face. Early
      diagnosis of SMMCI is important, since it may be a sign of other severe
      congenital or developmental abnormalities. Therefore, systematic follow-up and
      close monitoring of the growth and development of SMMCI patients is crucial. The
      purpose of this paper was  to report the cases of 2 children, each with a single
      median maxillary central incisor, and describe important symptoms of this
      syndrome that have not yet been reported.

PMID- 22583890
TI  - Fifteen-year follow-up of a conservatively managed, root-fractured permanent
      incisor.
AB  - The purpose of this case report was to describe the successful long-term
      conservative management of a root-fractured permanent maxillary right central
      incisor in an 8-year-old patient. After the initial approach of splinting the
      traumatized tooth, the patient was followed on a regular  basis for 15 years.
      Clinically, the crown of the root-fractured incisor showed no displacement or
      discoloration, and thermal tests suggested pulp vitality over the follow-up
      period. Radiographically, an increase in the diastasis was observed between the
      apical and coronal fragments due to  both the growth of the alveolar process and
      the healing with interposition of hard and soft tissue between the fragments and
      confirmed with computed tomography scan in the 15-year follow-up appointment.

PMID- 22583891
TI  - Liquid nitrogen cryosurgery for treatment of mucoceles in children.
AB  - A mucocele is a common benign lesion of the minor salivary gland mucosa that most
      frequently affects children and young adults. Several treatments have been
      described in the literature, including liquid nitrogen cryosurgery--a therapeutic
      alternative for treating mucoceles in children that has many applications in
      clinical oral pathology. The purpose of this paper was to present the treatment
      of lower lip mucoceles in 2 children via liquid nitrogen cryosurgery performed
      without local anesthesia. Also discussed are the mechanisms of action, current
      protocol of cryosurgery recommended in the management of mucoceles, clinical
      advantages and disadvantages, clinical outcomes, and pediatric patients' safety.

PMID- 22583892
TI  - Early complications with flexible intramedullary nailing in childhood fracture:
      100 cases managed with precurved tip and shaft nails.
AB  - BACKGROUND AND PURPOSE: Diaphyseal and metaphyseal fractures in children are
      frequently treated with the flexible intramedullary nailing (FIN) method. The aim
      of this study was to record postoperative complications and outcome in
      consecutive fracture patients treated with the new precurved tip and shaft nails
      and dedicated ergonomic instrumentation. METHODS: We report the analysis of 100
      consecutive fractures followed up for a minimum of 6 months. Ninety-seven
      children were included, comprising 77 shaft and 23 metaphyseal fractures.
      Demographic data, duration of surgery, nail and medullary canal diameter, date of
      nail removal, clinical assessment, follow-up radiographs and all complications
      were recorded. RESULTS: Mean age was 9.7 years, and mean body weight 35.1 kg.
      Twenty-one fractures had associated lesions. Mean duration of surgery was 42.4
      minutes. Nail removal was at a mean 6.1 months. Twelve percent of patients had
      complications, with six insufficient reductions, one delayed union, one non
      union, one iterative fracture, and three skin impingements. Unexpected surgical
      revision was required in seven cases. At follow-up, only one patient showed
      functional impairment, with 20 degrees  pronation loss, and three showed more
      than 10 degrees  axial deviation on X-ray. CONCLUSION: The low rate of skin
      impingement compared with the literature may be due to the new dedicated
      instruments. We believe that other complications can be avoided if one follows
      the FIN principles, avoiding weak assembly due to an insufficient nail/medullary
      canal diameter ratio, which is a limiting factor for indications in adolescents.
      The surgeons reported that precurved shaft nails facilitated the FIN procedure,
      although this subjective judgment may be due simply to the novelty of the nails.
      LEVEL OF EVIDENCE: Level IV. Retrospective study.

PMID- 22583893
TI  - Early correction of paediatric malunited distal metaphyseal radius fractures
      using percutaneous callus osteoclasis ("Calloclasis").
AB  - INTRODUCTION: Closed reduction of secondary displacements of distal metaphyseal
      radius fractures is an easy procedure only when performed within the first ten to
      fifteen days post-trauma, prior to the occurrence of malunion. When a hard bony
      callus prevents proper reduction, an open osteotomy is generally advocated.
      HYPOTHESIS: We suggest the use of a less invasive technique which aims at
      correcting early malunion when closed reduction is made impossible: the
      percutaneous callus osteoclasis. MATERIALS AND METHODS: Callus osteoclasis
      consists in a series of multiple bone-drilling in a postage stamp pattern
      performed under image intensifier using a large diameter pin, at a distance from
      the growth plate. Once the bone has been weakened, reduction is obtained by using
      the pin as an intrafocal lever. The pin is then pushed through the opposite
      cortex to ensure postero-lateral stabilization. RESULTS: Twenty-one patients were
      managed using this technique and reported good results with no complications.
      DISCUSSION: This technique offers a low aggressive management of malunions and
      may be performed within two to six weeks after trauma. LEVEL OF EVIDENCE: Level
      IV. Multicenter retrospective study.

PMID- 22583894
TI  - Early surgical anterior release for congenital and isolated elbow contracture in
      flexion: a case report of a 16-month-old child.
AB  - Isolated congenital elbow contracture is a rare upper-extremity disorder and
      there are few data about management of this condition. Authors report their
      experience after aggressive management of children with isolated congenital elbow
      contracture in flexion. Because of total absence of range of motion (ROM)
      improvement despites physical therapy (ROM 90-120 degrees ) and bone deformity,
      an anterior surgical release of the elbow was performed through an extensive
      lateral approach, at sixteen months of age. After surgery, this child was treated
      by three casts at maximal gained extension followed by sequential Turnbuckles
      splints. After five years of follow-up, the result was excellent with ROM 5-135
      degrees , normal function and absence of growth disturbance. The limiting factor
      of this protocol was excessive traction in elbow extension on the neurovascular
      structures, especially the radial nerve. This treatment represents an aggressive
      management with multiple general anaesthesia, but was found to be a valid option.

PMID- 22583895
TI  - Total shoulder arthroplasty - arthroplasty for glenohumeral arthropathies:
      results and complications after a minimum follow-up of 8 years according to the
      type of arthroplasty and etiology.
AB  - INTRODUCTION: Arthroplasty for glenohumeral arthropathies have specific
      complications and the final results are sometimes more dependent upon the type of
      shoulder arthroplasty than the initial etiology. The aim of our study was to
      evaluate the rate of complications and the functional improvement with different
      types of shoulder arthroplasties after a minimum follow-up of 8 years. MATERIALS
      AND METHODS: This was a multicenter retrospective study of 198 shoulders
      including 85 primary osteoarthritis of the shoulder, 76 cuff tear arthropathies,
      19 avascular necrosis and 18 rheumatoid arthritis. Arthroplasties included 104
      anatomic total shoulder arthroplasties (TSA), 77 reverse arthroplasties and 17
      hemiarthroplasties. Ten patients had their arthroplasty revised, and 134 patients
      with TSA were able to be present at the final follow-up or provide information on
      their case. Function was evaluated by the Constant-Murley score and loosening by
      standard radiographs. RESULTS: In the group with primary osteoarthritis of the
      shoulder, there were eight complications (11%) including six (8.3%) requiring
      implant revision. In the group of rotator cuff arthropathies, there were nine
      (14.7%) complications including four (6.5%) requiring implant revision. In the
      group with rheumatoid arthritis, there was one complication, and no surgical
      revision was necessary. There were no complications in the group with avascular
      necrosis. Glenoid migration occurred in 28.5% of anatomic TSA, and 3.4% of
      reverse arthroplasties. This difference was significant (P<0.001). The Constant
      Murley score was significantly improved in all etiologies. CONCLUSIONS:
      Glenohumeral arthropathies can be successfully treated by arthroplasty. Anatomic
      TSA was shown to be associated with a high risk of glenoid loosening at
      radiographic follow-up, which makes us hesitate to use the cemented polyethylene
      implant, especially in young patients. LEVEL OF EVIDENCE: IV - Retrospective
      study.

PMID- 22583896
TI  - Catalposide is a natural agonistic ligand of peroxisome proliferator-activated
      receptor-alpha.
AB  - Peroxisome proliferator-activated receptor-alpha (PPARalpha) is a nuclear
      receptor that regulates the expression of genes related to cellular lipid uptake
      and oxidation. Thus, PPARalpha agonists may be important in the treatment of
      hypertriglyceridemia and hepatic steatosis. In this study, we demonstrated that
      catalposide is a novel natural PPARalpha agonist, identified from reporter gene
      assay-based activity screening with approximately 900 natural plant and seaweed
      extracts. Results of time-resolved fluorescence resonance energy transfer
      analyses suggested that the compound interacted directly with the ligand-binding
      domain of PPARalpha. Cultured hepatocytes stimulated with catalposide exhibited
      significantly reduced cellular triglyceride concentrations, by 21%, while
      cellular uptake of fatty acids was increased, by 70% (P<0.05). Quantitative PCR
      analysis revealed that the increase in cellular fatty acid uptake was due to
      upregulation of fatty acid transporter protein-4 (+19% vs. the control) in cells
      stimulated with catalposide. Additionally, expression of genes related to fatty
      acid oxidation and high-density lipoprotein metabolism were upregulated, while
      that of genes related to fatty acid synthesis were suppressed. In conclusion,
      catalposide is hypolipidemic by activation of PPARalpha via a ligand-mediated
      mechanism that modulates the expression of in lipid metabolism genes in
      hepatocytes.

PMID- 22583897
TI  - Murine calvaria-derived progenitor cells express high levels of osterix and lose
      their adipogenic capacity.
AB  - Though the mouse is the most widely used biomedical animal model, it is difficult
      to isolate murine mesenchymal stem cells (MSCs) from the bone marrow because of
      contamination by hematopoietic cells. The murine compact bone tissue of long
      bones is considered a novel and reliable source of MSCs with low hematopoietic
      cell contamination. We investigated whether the murine compact bone of the
      calvaria would be a promising source of MSCs due to its low bone marrow content.
      We isolated cells from both long bones and the calvaria using the same method.
      Although they shared morphological features and surface antigens similar to those
      of long bone-derived MSCs, the calvaria-derived cells highly expressed the
      osteogenic transcription factor osterix, lost their adipogenic capacity and
      gained a higher osteogenic capacity. These findings suggest that the cells that
      migrated from the calvaria were progenitor cells rather than MSCs and that the
      differentiation fate of mesenchymal stem/progenitor cells existing in different
      murine compact bone deposits is already committed.

PMID- 22583898
TI  - Protective effect of L-theanine on carbon tetrachloride-induced acute liver
      injury in mice.
AB  - We studied effects of L-theanine, a unique amino acid in tea, on carbon
      tetrachloride (CCl(4))-induced liver injury in mice. The mice were pre-treated
      orally with L-theanine (50, 100 or 200 mg/kg) once daily for seven days before
      CCl(4) (10 ml/kg of 0.2% CCl(4) solution in olive oil) injection. L-theanine dose
      dependently suppressed the increase of serum activity of ALT and AST and
      bilirubin level as well as liver histopathological changes induced by CCl(4) in
      mice. L-theanine significantly prevented CCl(4)-induced production of lipid
      peroxidation and decrease of hepatic GSH content and antioxidant enzymes
      activities. Our further studies demonstrated that L-theanine inhibited metabolic
      activation of CCl(4) through down-regulating cytochrome P450 2E1 (CYP2E1). As a
      consequence, L-theanine inhibited oxidative stress-mediated inflammatory response
      which included the increase of TNF-alpha and IL-1beta in sera, and expression of
      cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in livers.
      CCl(4)-induced activation of apoptotic related proteins including caspase-3 and
      PARP in mouse livers was also prevented by L-theanine treatment. In summary, L
      theanine protects mice against CCl(4)-induced acute liver injury through
      inhibiting metabolic activation of CCl(4) and preventing CCl(4)-induced reduction
      of anti-oxidant capacity in mouse livers to relieve inflammatory response and
      hepatocyte apoptosis.

PMID- 22583899
TI  - Regulation of the FABP7 gene by PAX6 in malignant glioma cells.
AB  - Brain fatty acid-binding protein (FABP7) and PAX6 are both expressed in radial
      glial cells and have been implicated in neurogenesis and glial cell
      differentiation. FABP7 and PAX6 have also been postulated to play a role in
      malignant glioma cell growth and invasion. Here, we address the role of PAX6 in
      regulating FABP7 gene expression in malignant glioma cells. We report that PAX6
      and FABP7 RNA are generally co-expressed in malignant glioma cell lines, tumors
      and tumor neurospheres. Using the CAT reporter gene assay, we show that FABP7
      promoter activity is upregulated by PAX6. Sequential deletion analysis of the
      FABP7 promoter, combined with gel shift and supershift assays demonstrate the
      presence of a PAX6 responsive region located upstream of the FABP7 gene, at -862
      to -1033 bp. Inclusion of sequences between -1.2 and -1.8 kb reduced CAT
      activity, suggesting the presence of a repressor element within this region.
      While PAX6 overexpression did not induce endogenous FABP7 expression in FABP7
      negative cells, knock-down of PAX6 in PAX6-positive malignant glioma cells
      resulted in reduced FABP7 levels. These data provide the first evidence of direct
      transactivation of the FABP7 proximal promoter by PAX6 and suggest a synergistic
      mechanism for PAX6 and other co-factor(s) in regulating FABP7 expression in
      malignant glioma.

PMID- 22583900
TI  - Disruption of the mu-delta opioid receptor heteromer.
AB  - The crystal structure of the mu and kappa opioid receptors has revealed dimeric
      structural arrangements. Mu-delta receptors heteromers also exist and we have
      identified discrete cytoplasmic regions in each receptor required for oligomer
      formation. In the carboxyl tail of the delta receptor we identified three glycine
      residues (-GGG), substitution of any of these residues prevented heteromer
      formation. In intracellular loop 3 of both mu and delta receptors we identified
      three residues (-SVR), substitution of any of these residues prevented heteromer
      formation.

PMID- 22583902
TI  - Formation and mechanical characterization of aminoplast core/shell microcapsules.
AB  - This work aims at establishing a link between process conditions and resulting
      micromechanical properties for aminoplast core/shell microcapsules. The
      investigated capsules were produced by the in situ polymerization of melamine
      formaldehyde resins, which represents a widely used and industrially relevant
      approach in the field of microencapsulation. Within our study, we present a
      quantitative morphological analysis of the capsules' size and shell thickness.
      The diameter of the investigated capsules ranged from 10 to 50 MUm and the shell
      thickness was found in a range between 50 and 200 nm. As key parameter for the
      control of the shell thickness, we identified the amount of amino resin per total
      surface area of the dispersed phase. Mechanical properties were investigated
      using small deformations on the order of the shell thickness by atomic force
      microscopy with a colloidal probe setup. The obtained capsule stiffness increased
      with an increasing shell thickness from 2 to 30 N/m and thus showed the same
      trend on the process parameters as the shell thickness. A simple analytical model
      was adopted to explain the relation between capsules' geometry and mechanics and
      to estimate the elastic modulus of the shell about 1.7 GPa. Thus, this work
      provides strategies for a rational design of microcapsule mechanics. 

PMID- 22583901
TI  - Thrombospondin-1 inhibits osteogenic differentiation of human mesenchymal stem
      cells through latent TGF-beta activation.
AB  - Transforming growth factor-beta (TGF-beta) is a critical regulator of bone
      development and remodeling. TGF-beta must be activated from its latent form in
      order to signal. Thrombospondin-1 (TSP1) is a major regulator of latent TGF-beta
      activation and TSP1 control of TGF-beta activation is critical for regulation of
      TGF-beta activity in multiple diseases. Bone marrow-derived mesenchymal stem
      cells (MSCs) have osteogenic potential and they participate in bone remodeling in
      injury and in response to tumor metastasis. Since both TSP1 and TGF-beta inhibit
      osteoblast differentiation, we asked whether TSP1 blocks osteoblast
      differentiation of MSCs through its ability to stimulate TGF-beta activation.
      TSP1 added to human bone marrow-derived MSCs under growth conditions increases
      active TGF-beta. Cultured MSCs express TSP1 and both TSP1 expression and TGF-beta
      activity decrease during osteoblast differentiation. TSP1 and active TGF-beta
      block osteoblast differentiation of MSCs grown in osteogenic media as measured by
      decreased Runx2 and alkaline phosphatase expression. The inhibitory effect of
      TSP1 on osteoblast differentiation is due to its ability to activate latent TGF
      beta, since a peptide which blocks TSP1 TGF-beta activation reduced TGF-beta
      activity and restored osteoblast differentiation as measured by increased Runx2
      and alkaline phosphatase expression. Anti-TGF-beta neutralizing antibody also
      increased alkaline phosphatase expression in the presence of TSP1. These studies
      show that TSP1 regulated TGF-beta activity is a critical determinant of
      osteoblast differentiation.

PMID- 22583903
TI  - Prognostic factors in patients with idiopathic portal hypertension: Two Japanese
      nationwide epidemiological surveys in 1999 and 2005.
AB  - AIM:   To investigate factors affecting disease prognosis among patients with
      idiopathic portal hypertension (IPH). METHODS:   Two Japanese nationwide
      epidemiological surveys on IPH were conducted in 1999 and 2005. Analyzing data
      from each cross-sectional survey separately, we examined the consistent
      prognostic factors detected from each analysis and assessed the effect of
      treatments for varices on IPH prognosis. Outcome was the disease condition at
      last observation compared with that at diagnosis, categorized into two levels
      (recovered/improved and unchanged/aggravated/deceased). To evaluate the
      association with each characteristic, we calculated adjusted odds ratio (OR) and
      95% confidence interval (CI) using a binary model for logistic regression.
      RESULTS:   Among 160 patients with IPH in 1999 and 85 in 2005, 10% had aggravated
      disease at a mean of 6-7 years after the diagnosis. Statistically significant ORs
      were observed for two factors: esophageal varices, especially of F(2-3)  stage,
      at diagnosis (OR = 6.83, 95% CI = 2.10-22.1 in 1999; OR = 10.7, 95% CI = 1.08-105
      in 2005) ameliorated IPH; and hepatic encephalopathy at diagnosis (OR = 0.19, 95%
      CI = 0.03-1.04 in 1999; crude OR = 0.05, 95% CI = 0.01-0.60 in 2005 using a
      proportional odds model) worsened IPH. Further analyses explained that the
      apparent ameliorating effect of esophageal varices was due to the effect of
      subsequent treatment (OR = 4.59, 95% CI = 0.89-23.7 in 2005). CONCLUSION:   The
      prognosis of IPH would be better if varices were adequately controlled. Patients
      with liver failure at diagnosis would be at high risk for subsequent disease
      aggravation.

PMID- 22583904
TI  - Inhibitory effects of luteolin on titanium particle-induced osteolysis in a mouse
      model.
AB  - Wear particles liberated from the surfaces of an implanted prosthesis are
      associated with peri-implant osteolysis and subsequent aseptic loosening. In the
      latter wear particle-induced inflammation and osteoclastogenesis have been
      identified as critical factors, and their inhibition as important steps in the
      treatment of affected patients, such as those undergoing total hip replacement.
      In this study the ability of luteolin to inhibit both titanium (Ti) particle
      induced osteoclastogenesis in vitro and osteolysis in a murine calvaria Ti
      particle-induced model of osteolysis was examined. The results showed that
      luteolin, a highly potent and efficient inhibitor of tumor necrosis factor alpha
      (TNF-alpha) and interleukin-6 expression, inhibited Ti particle-induced
      inflammatory cytokine release, osteoclastogenesis, and bone resorption in bone
      marrow macrophages. Microcomputed tomography and histological analyses showed
      that the Ti particles caused significant bone resorption and increased TRAP(+)
      multinuclear osteoclasts in the murine calvarial model of osteolysis, whereas
      this was not the case in the luteolin treatment group, in which osteolytic
      suppression was accompanied by a decrease in both TNF-alpha production and serum
      levels of the osteoclast marker the C-terminal telopeptide fragment of type I
      collagen. These results support the use of luteolin as a natural compound in the
      prevention and treatment of aseptic loosening after total replacement
      arthroplasty.

PMID- 22583905
TI  - Climate envelope modelling reveals intraspecific relationships among flowering
      phenology, niche breadth and potential range size in Arabidopsis thaliana.
AB  - Species often harbour large amounts of phenotypic variation in ecologically
      important traits, and some of this variation is genetically based. Understanding
      how this genetic variation is spatially structured can help to understand
      species' ecological tolerances and range limits. We modelled the climate
      envelopes of Arabidopsis thaliana genotypes, ranging from early- to late
      flowering, as a function of several climatic variables. We found that genotypes
      with contrasting alleles at individual flowering time loci differed significantly
      in potential range size and niche breadth. We also found that later flowering
      genotypes had more restricted range potentials and narrower niche breadths than
      earlier flowering genotypes, indicating that local selection on flowering can
      constrain or enhance the ability of populations to colonise other areas. Our
      study demonstrates how climate envelope models that incorporate ecologically
      important genetic variation can provide insights into the macroecology of a
      species, which is important to understand its responses to changing environments.

PMID- 22583906
TI  - Kinematic evaluation of patients with total and reverse shoulder arthroplasty
      during rehabilitation exercises with different loads.
AB  - BACKGROUND: Following shoulder arthroplasty, any well-planned rehabilitation
      program should include muscle strengthening. However, it is not always clear how
      different external loads influence shoulder kinematics in patients with shoulder
      prostheses. The objective of this study was to describe shoulder kinematics and
      determine the contribution of the scapulothoracic joint to total shoulder motion
      of patients with total and reverse shoulder arthroplasties and of healthy
      individuals during rehabilitation exercises (anteflexion and elevation in the
      scapular plane) using different loading conditions (without external load, 1 kg
      and elastic resistance). METHODS: Shoulder motions were measured using an
      electromagnetic tracking device. A force transducer was used to record force
      signals during loaded conditions using elastic resistance. Statistical
      comparisons were made using a three-way repeated-measures analysis of variance
      with a Bonferroni post hoc testing. FINDINGS: The scapula contributed more to
      movement of the arm in subjects with prostheses compared to healthy subjects. The
      same applies for loaded conditions (1 kg and elastic resistance) relative to
      unloaded tasks. For scapular internal rotation, upward rotation and posterior
      tilt no significant differences among groups were found during both exercises.
      Glenohumeral elevation angles during anteflexion were significantly higher in the
      total shoulder arthroplasty group compared to the reverse shoulder arthroplasty
      group. INTERPRETATION: Differences in contribution of the scapula to total
      shoulder motion between patients with different types of arthroplasties were not
      significant. However, compared to healthy subjects, they were. Furthermore,
      scapular kinematics of patients with shoulder arthroplasty was influenced by
      implementation of external loads, but not by the type of load.

PMID- 22583908
TI  - Urinary engrailed-2 (EN2) levels predict tumour volume in men undergoing radical
      prostatectomy for prostate cancer.
AB  - What's known on the subject? and What does the study add? There are a lot of
      potential prostate cancer biomarkers being evaluated. All aim to improve on the
      sensitivity and specificity of PSA. EN2 was recently shown by our group to have
      better sensitivity and specificity than PSA. EN2 is a simple ELISA test and is
      not dependent on other parameters, even PSA, unlike all the other current
      biomarkers under evaluation. To date, no marker correlates with the amount of
      cancer present - the present study shows this positive correlation with EN2 in
      men undergoing prostatectomy. The potential utility of this work is that by
      knowing that the level of EN2 corresponds to the amount of cancer present,
      irrelevant of tumour grade and number of cancer foci, we can define an EN2 level
      corresponding to small cancers, which can then undergo surveillance. We are
      conducting a further study that is aimed at determining whether the levels of EN2
      in urine can indicate 'significant' vs 'non-significant cancer' using the
      threshold of 0.5 mL cancer (after Epstein's work). OBJECTIVES: To evaluate the
      relationship between levels of a recently described prostate cancer biomarker
      engrailed-2 (EN2) in urine and cancer volume in men who had undergone radical
      prostatectomy (RP) for prostate cancer. To date, prostate-specific antigen (PSA)
      levels have not reliably predicted prostate cancer volume. Reliable volume
      indicator biomarker(s) may aid management decisions, e.g. active treatment vs
      active surveillance. PATIENTS AND METHODS: Archived patient samples from the
      Aarhus Prostate Cancer Project, Denmark, were assessed. Pre-treatment mid-stream
      urines, without preceding prostatic massage, were collected and stored at -80 
      degrees C. Urinary EN2 levels were measured by a recently published enzyme-linked
      immunosorbent assay. RESULTS: In all, 88 of the whole cohort of 125 men (70%)
      were positive for EN2 in their urine (>42.5 ug/L); 38/58 (65%) men where cancer
      volume data was available. There was no statistical relationship between urinary
      EN2 levels and serum PSA levels. PSA levels did not correlate with tumour stage,
      combined Gleason grade, total prostatic weight or cancer volume. There was a
      strong statistical relationship between urinary EN2 and prostate cancer volume by
      linear regression (P = 0.006). Higher EN2 levels correlated with tumour stage T1
      vs T2 (P = 0.027). CONCLUSIONS: Pre-surgical urinary EN2 levels were associated
      with increasing tumour stage and closely reflected the volume of cancer in RP
      specimens. Given the ease of collection (no prostatic massage required) and the
      simplicity, low cost and robustness of the assay, EN2 may become a useful
      biomarker in not only identifying which patients have prostate cancer but may
      also facilitate risk stratification by indicating the burden of tumour volume.

PMID- 22583907
TI  - On stabilization of loosened hip stems via cement injection into osteolytic
      cavities.
AB  - BACKGROUND: Cement injection into osteolytic areas around the cement mantle is a
      technique for refixation of loose hip implants for patients who cannot undergo
      standard revision surgery. Preliminary clinical results show the improvement in
      walking distance, patients' independence and pain relief. METHODS: In this study,
      we use a detailed finite element model to analyze whether cement injection into
      osteolytic areas contributes to the overall implant stability. We study the
      effect of various factors, like location and size of osteolytic areas, interface
      conditions and bone stiffness on bone-cement relative motion. FINDINGS: Presented
      results demonstrate that the procedure is most effective for the osteolytic areas
      located in the proximal region of the femur, while factors like a thin layer of
      residual fibrous tissue around the injected cement, that was not removed during
      the surgery, combined with reduced bone stiffness reduce the efficiency of the
      procedure. INTERPRETATION: Cement injection is able to stabilize loosened hip
      prostheses. However, it is important to remove the fibrous tissue layer
      completely, as even a thin layer will negatively influence stabilization. We will
      focus our research efforts on developing fibrous tissue removal techniques in
      order to optimize this minimally invasive treatment.

PMID- 22583909
TI  - Application of the Random Forest method to analyse epidemiological and phenotypic
      characteristics of Salmonella 4,[5],12:i:- and Salmonella Typhimurium strains.
AB  - Salmonella enterica 4,[5],12:i:- is a monophasic variant of S. Typhimurium. In
      the last decade, its prevalence rose sharply. Although S. 4,[5],12:i:- and S.
      Typhimurium are known to pose a considerable public health risk, there is no
      detailed information on the circulation of these serovars in Italy, particularly
      as far as veterinary isolates are concerned. For this reason, a data set of 877
      strains isolated in the north-east of Italy from foodstuffs, animals and
      environment was analysed during 2005-2010. The Random Forests (RF) method was
      used to identify the most important epidemiological and phenotypic variables to
      show the difference between the two serovars. Both descriptive analysis and RF
      revealed that S. 4,[5],12:i:- is less heterogeneous than S. Typhimurium. RF
      highlighted that phage type was the most important variable to differentiate the
      two serovars. The most common phage types identified for S. 4,[5],12:i:- were
      DT20a, U311 and DT193. The same phage types were also found in S. Typhimurium
      isolates, although with a much lower prevalence. DT7 and DT120 were ascribed to
      the two serovars at comparable levels. DT104, DT2 and DT99 were ascribed
      exclusively to S. Typhimurium, and almost all the other phage types identified
      were more related to the latter serovar. Such data confirm that phage typing can
      provide an indication of the biphasic or monophasic state of the strains
      investigated and could therefore support serotyping results. However, phage
      typing cannot be used as the definitive method to differentiate the two serovars,
      as part of the phage types were detected for both serovars and, in particular,
      all phage types found for S. 4,[5],12:i- were found also for S. Typhimurium.

PMID- 22583911
TI  - Aid effectiveness from Rome to Busan: some progress but lacking bottom-up
      approaches or behaviour changes.
AB  - The Busan partnership adopted at the 4th High Level Forum on Aid Effectiveness at
      the end of last year is a significant step forward towards the improvement of aid
      quality and the promotion of development. In particular, the inclusiveness
      achieved in Busan and the shift in discourse from 'aid effectiveness' to
      'development effectiveness' are emblematic. However, key challenges still remain.
      Firstly, decision-making should be more bottom-up, finding ways to take into
      account the populations' needs and experiences and to enhance self-learning
      dynamics during the policy process. Today, it is particularly necessary to define
      what 'development' means at country level, according to the aspirations of
      particular categories of people and meeting operational and local expectations.
      Secondly, changes in language should be followed by a real change in mindset.
      Development stakeholders should further adapt their procedures to the reality of
      complex systems in which development interventions are being dealt with.

PMID- 22583910
TI  - Metabolic syndrome in central Brazil: prevalence and correlates in the adult
      population.
AB  - BACKGROUND: The prevalence of metabolic syndrome (MetS) has increased in
      developing countries in recent decades. This syndrome, a clustering of metabolic
      abnormalities, has been correlated to various socioeconomic and behavioral
      variables. We investigated the prevalence and prevalence ratios (PR) of MetS and
      related factors in an adult population of the Federal District (FD) of Brazil,
      which is located in the central region of the country. METHODS: A cross
      sectional, population-based study conducted in 2007, with 2130 adults (aged 18
      years or older) in the FD of Brazil. Metabolic syndrome was defined according to
      the recently harmonized criteria. The prevalence of MetS and PR were estimated
      for each sex according to the diagnostic components and the overall contribution
      of the selected correlates. RESULTS: The overall prevalence of MetS was 32.0%
      (95%CI: 28.9-35.2), with no gender difference. The single component with the
      greatest contribution to the diagnosis of MetS was hypertension in men (PR 5.10,
      95%CI: 3.17-8.22) and high waist circumference in women (PR 5.02, 95%CI: 3.77
      6.69). The prevalence of MetS increased significantly and progressively with age
      and excess weight. In women, higher education was protective against MetS (PR
      0.66, 95%CI: 0.49-0.89) compared to 8 or less years of education. There was no
      association between the prevalence of MetS and behavioral variables studied.
      CONCLUSIONS: This study provides comprehensive and alarming data about the
      prevalence of MetS among the adult population of Brazil's FD. The results suggest
      that reducing education inequalities may be an important public policy goal to
      improve health outcomes, especially among women.

PMID- 22583912
TI  - Application of hypoiodite-mediated aminyl radical cyclization to synthesis of
      solasodine acetate.
AB  - Solasodine acetate, an anticancer steroidal alkaloid, was synthesized from
      diosgenin in 8 steps with an overall yield of 23%. A key synthetic step involves
      the formation of 5/6-oxazaspiroketal moiety via hypoiodite-mediated aminyl
      radical cyclization of a steroidal primary amine.

PMID- 22583913
TI  - The use of cortical spreading depression for studying the brain actions of
      antioxidants.
AB  - OBJECTIVES: We review the main adverse effects of reactive oxygen species (ROS)
      in the mammalian organism, introducing the reader on the worldwide problem of the
      ROS neurophysiological impact on the developing and the adult brain, and
      discussing the neuroprotective action  of antioxidant molecules. METHODS: We
      briefly present the electrophysiological phenomenon designated as 'cortical
      spreading depression' (CSD), as a parameter of normal brain functioning. We
      highlight recent electrophysiological advances obtained in experimental  studies
      from our laboratory and from others, showing how to investigate the ROS effects
      on the brain by using the CSD phenomenon. RESULTS: Under conditions such as
      aging, ROS production by photo-activation of dye molecules and ethanol
      consumption, we describe the effects,  on CSD, of treating animals with (1)
      antioxidants and (2) with antioxidant-deficient diets. DISCUSSION: The current
      understanding of how ROS affect brain electrophysiological activity and the
      possible interaction between these ROS effects and those effects of altered
      nutritional  status of the organism are discussed.

PMID- 22583915
TI  - Dietary rice bran promotes resistance to Salmonella enterica serovar Typhimurium
      colonization in mice.
AB  - BACKGROUND: Dietary rice bran consists of many bioactive components with disease
      fighting properties; including the capacity to modulate the gut microbiota.
      Studies point to the important roles of the gut microbiota and the mucosal
      epithelium in the establishment of protection against enteric pathogens, such as
      Salmonella. The ability of rice bran to reduce the susceptibility of mice to a
      Salmonella infection has not been previously investigated. Therefore, we
      hypothesized that the incorporation of rice bran into the diet would inhibit the
      colonization of Salmonella in mice through the induction of protective mucosal
      responses. RESULTS: Mice were fed diets containing 0%, 10% and 20% rice bran for
      one week prior to being orally infected with Salmonella enterica serovar
      Typhimurium. We found that mice consuming the 10 and 20% rice bran diets
      exhibited a reduction in Salmonella fecal shedding for up to nine days post
      infection as compared to control diet fed animals (p < 0.05). In addition, we
      observed decreased concentrations of the pro-inflammatory cytokines, TNF-alpha,
      IFN-gamma, and IL-12 (p < 0.05) as well as increased colonization of native
      Lactobacillus spp. in rice bran fed mice (p < 0.05). Furthermore, in vitro
      experiments revealed the ability of rice bran extracts to reduce Salmonella entry
      into mouse small intestinal epithelial cells. CONCLUSIONS: Increasing rice bran
      consumption represents a novel dietary means for reducing susceptibility to
      enteric infection with Salmonella and potentially via induction of native
      Lactobacillus spp.

PMID- 22583916
TI  - Brain functional abnormality in schizo-affective disorder: an fMRI study.
AB  - BACKGROUND: Schizo-affective disorder has not been studied to any significant
      extent using functional imaging. The aim of this study was to examine patterns of
      brain activation and deactivation in patients meeting strict diagnostic criteria
      for the disorder. METHOD: Thirty-two patients meeting research diagnostic
      criteria (RDC) for schizo-affective disorder (16 schizomanic and 16
      schizodepressive) and 32 matched healthy controls underwent functional magnetic
      resonance imaging (fMRI) during performance of the n-back task. Linear models
      were used to obtain maps of activations and deactivations in the groups. RESULTS:
      Controls showed activation in a network of frontal and other areas and also
      deactivation in the medial frontal cortex, the precuneus and the parietal cortex.
      Schizo-affective patients activated significantly less in prefrontal, parietal
      and temporal regions than the controls, and also showed failure of deactivation
      in the medial frontal cortex. When task performance was controlled for, the
      reduced activation in the dorsolateral prefrontal cortex (DLPFC) and the failure
      of deactivation of the medial frontal cortex remained significant. CONCLUSIONS:
      Schizo-affective disorder shows a similar pattern of reduced frontal activation
      to schizophrenia. The disorder is also characterized by failure of deactivation
      suggestive of default mode network dysfunction.

PMID- 22583914
TI  - N-terminal phosphorylation of protein phosphatase 2A/Bbeta2 regulates
      translocation to mitochondria, dynamin-related protein 1 dephosphorylation, and
      neuronal survival.
AB  - The neuron-specific Bbeta2 regulatory subunit of protein phosphatase 2A (PP2A), a
      product of the spinocerebellar ataxia type 12 disease gene PPP2R2B, recruits
      heterotrimeric PP2A to the outer mitochondrial membrane (OMM) through its N
      terminal mitochondrial targeting sequence. OMM-localized PP2A/Bbeta2 induces
      mitochondrial fragmentation, thereby increasing susceptibility to neuronal
      insults. Here, we report that PP2A/Bbeta2 activates the mitochondrial fission
      enzyme dynamin-related protein 1 (Drp1) by dephosphorylating Ser656, a highly
      conserved inhibitory phosphorylation site targeted by the neuroprotective protein
      kinase A-A kinase anchoring protein 1 complex. We further show that translocation
      of PP2A/Bbeta2 to mitochondria is regulated by phosphorylation of Bbeta2 at three
      N-terminal serines. Phosphomimetic substitution of Ser20, Ser21, and Ser22
      renders Bbeta2 cytosolic, blocks Drp1 dephosphorylation and mitochondrial
      fragmentation, and abolishes the ability of Bbeta2 overexpression to induce
      apoptosis in cultured hippocampal neurons. Alanine substitution of Ser20-Ser22 to
      prevent phosphorylation has the opposite effect, promoting association of Bbeta2
      with mitochondria, Drp1 dephosphorylation, mitochondrial fission, and neuronal
      death. OMM translocation of Bbeta2 can be attenuated by mutation of residues in
      close proximity to the catalytic site, but only if Ser20-Ser22 are available for
      phosphorylation, suggesting that PP2A/Bbeta2 autodephosphorylation is necessary
      for OMM association, probably by uncovering the net positive charge of the
      mitochondrial targeting sequence. These results reveal another layer of
      complexity in the regulation of the mitochondrial fission-fusion equilibrium and
      its physiological and pathophysiological consequences in the nervous system.

PMID- 22583917
TI  - Children eat their school lunch too quickly: an exploratory study of the effect
      on food intake.
AB  - BACKGROUND: Speed of eating, an important aspect of eating behaviour, has
      recently been related to loss of control of food intake and obesity. Very little
      time is allocated for lunch at school and thus children may consume food more
      quickly and food intake may therefore be affected. Study 1 measured the time
      spent eating lunch in a large group of students eating together for school meals.
      Study 2 measured the speed of eating and the amount of food eaten in individual
      school children during normal school lunches and then examined the effect of
      experimentally increasing or decreasing the speed of eating on total food intake.
      METHODS: The time spent eating lunch was measured with a stop watch in 100
      children in secondary school. A more detailed study of eating behaviour was then
      undertaken in 30 secondary school children (18 girls). The amount of food eaten
      at lunch was recorded by a hidden scale when the children ate amongst their peers
      and by a scale connected to a computer when they ate individually. When eating
      individually, feedback on how quickly to eat was visible on the computer screen.
      The speed of eating could therefore be increased or decreased experimentally
      using this visual feedback and the total amount of food eaten measured. RESULTS:
      In general, the children spent very little time eating their lunch. The 100
      children in Study 1 spent on average (SD) just 7 (0.8) minutes eating lunch. The
      girls in Study 2 consumed their lunch in 5.6 (1.2) minutes and the boys ate
      theirs in only 6.8 (1.3) minutes. Eating with peers markedly distorted the amount
      of food eaten for lunch; only two girls and one boy maintained their food intake
      at the level observed when the children ate individually without external
      influences (258 (38) g in girls and 289 (73) g in boys). Nine girls ate on
      average 33% less food and seven girls ate 23% more food whilst the remaining boys
      ate 26% more food. The average speed of eating during school lunches amongst
      groups increased to 183 (53)% in the girls and to 166 (47)% in the boys compared
      to the speed of eating in the unrestricted condition. These apparent changes in
      food intake during school lunches could be replicated by experimentally
      increasing the speed of eating when the children were eating individually.
      CONCLUSIONS: If insufficient time is allocated for consuming school lunches,
      compensatory increased speed of eating puts children at risk of losing control
      over food intake and in many cases over-eating. Public health initiatives to
      increase the time available for school meals might prove a relatively easy way to
      reduce excess food intake at school and enable children to eat more healthily.

PMID- 22583918
TI  - Collision metastasis of urothelial and prostate carcinomas to the same lymph
      node: a case report and review of the literature.
AB  - INTRODUCTION: A collision tumor is the meeting and eventual intermingling of two
      malignant neoplasms arising from independent topographical sites. Collision
      metastasis of carcinomas in the lymph nodes is a rare event. A literature search
      revealed only three cases of such a collision metastasis of prostatic and
      urothelial carcinoma, and only one of those cases had used immunohistochemical
      stains to distinguish the two tumors. CASE PRESENTATION: We encountered a case of
      this rare entity in an 83-year-old African-American man who presented to our
      facility with increasing pelvic pain after a transurethral resection of a high
      grade bladder tumor and a negative metastatic computed tomography chest, abdomen
      and pelvic scan investigation. A radical cystoprostatectomy was subsequently
      performed revealing a multi-centric, high-grade, ill-defined infiltrating
      urothelial carcinoma infiltrating the right pericystic soft tissue. A
      histopathological examination of the prostate revealed a multi-centric
      adenocarcinoma (Gleason 4 + 4) involving two pelvic lymph nodes. Interestingly,
      while the right pelvic lymph node was positive for metastatic prostatic
      adenocarcinoma alone, immunohistochemical studies of the left pelvic lymph node
      revealed a dual metastatic urothelial (cytokeratin-7 and pan-cytokeratin
      positive, prostate-specific antigen and cytokeratin-20 negative) and prostatic
      (prostate-specific antigen and pan-cytokeratin positive, cytokeratin-7 and
      cytokeratin-20 negative) carcinoma. CONCLUSIONS: The collision of metastatic
      urothelial carcinoma and prostatic adenocarcinoma is unusual, and their
      biological behavior remains uncertain. A high index of suspicion along with
      thorough clinical examination and immunohistochemical stain results are an
      integral part of differentiating collision of urothelial carcinoma from prostate
      carcinoma, particularly when the two tumors are in close proximity with
      overlapping histological features.

PMID- 22583919
TI  - Temporal bone characterization and cochlear implant feasibility in the common
      marmoset (Callithrix jacchus).
AB  - The marmoset (Callithrix jacchus) is a valuable non-human primate model for
      studying behavioral and neural mechanisms related to vocal communication. It is
      also well suited for investigating neural mechanisms related to cochlear
      implants. The purpose of this study was to characterize marmoset temporal bone
      anatomy and investigate the feasibility of implanting a multi-channel
      intracochlear electrode into the marmoset scala tympani. Micro computed
      tomography (microCT) was used to create high-resolution images of marmoset
      temporal bones. Cochlear fluid spaces, middle ear ossicles, semicircular canals
      and the surrounding temporal bone were reconstructed in three-dimensional space.
      Our results show that the marmoset cochlea is ~16.5 mm in length and has ~2.8
      turns. The cross-sectional area of the scala tympani is greatest (~0.8 mm(2)) at
      ~1.75 mm from the base of the scala, reduces to ~0.4 mm(2) at 5 mm from the base,
      and decreases at a constant rate for the remaining length. Interestingly, this
      length-area profile, when scaled 2.5 times, is similar to the scala tympani of
      the human cochlea. Given these dimensions, a compatible multi-channel implant
      electrode was identified. In a cadaveric specimen, this electrode was inserted
      3/4 turn into the scala tympani through a cochleostomy at ~1 mm apical to the
      round window. The depth of the most apical electrode band was ~8 mm. Our study
      provides detailed structural anatomy data for the middle and inner ear of the
      marmoset, and suggests the potential of the marmoset as a new non-human primate
      model for cochlear implant research.

PMID- 22583920
TI  - Mechanical properties of human tympanic membrane in the quasi-static regime from
      in situ point indentation measurements.
AB  - The tympanic membrane is a key component of the human auditory apparatus. Good
      estimates of tympanic membrane mechanical properties are important to obtain
      realistic models of middle ear mechanics. Current literature values are almost
      all derived from direct mechanical tests on cut-out strips. For a biomedical
      specimen like the tympanic membrane, it is not always possible to harvest strips
      of uniform and manageable geometry and well-defined size suitable for such
      mechanical tests. In this work, elastic and viscoelastic properties of human
      tympanic membrane were determined through indentation testing on the tympanic
      membrane in situ. Indentation experiments were performed on three specimens with
      a custom-built apparatus that was also used in previously published works. Two
      types of indentation tests were performed on each specimen: (i) sinusoidal
      indentation at 0.2 Hz yielding the quasi-static Young's modulus and (ii) step
      indentation tests yielding viscoelastic properties in the quasi-static regime (0
      20 Hz). In the cyclic indentation experiments (type i), the indentation depth and
      resulting needle force were recorded. The unloaded shape of the tympanic membrane
      and the membrane thickness were measured and used to create a specimen-specific
      finite element model of the experiment. The Young's modulus was then found
      through optimization of the error between model and experimental data; the values
      that were found for the three different samples are 2.1 MPa, 4.4 MPa and 2.3 MPa.
      A sensitivity analysis showed that these values are very sensitive to the
      thickness used in the models. In the step indentation tests (type ii), force
      relaxation was measured during 120 s and the relaxation curves were fitted with a
      5 parameter Maxwell viscoelastic model. The relaxation curves in the time domain
      were transformed to complex moduli in the frequency domain, yielding viscoelastic
      properties in the quasi-static regime only.

PMID- 22583921
TI  - Spread of excitation varies for different electrical pulse shapes and stimulation
      modes in cochlear implants.
AB  - In cochlear implants (CI) bipolar (BP) electrical stimulation has been suggested
      as a method to reduce the spread of current along the cochlea. However,
      behavioral measurements in BP mode have shown either similar or worse performance
      than in monopolar (MP) mode. This could be explained by a bimodal excitation
      pattern, with two main excitation peaks at the sites of the stimulating
      electrodes. We measured the spread of excitation (SOE) by means of the
      electrically evoked compound action potential (ECAP), obtained using the forward
      masked paradigm. The aim was to measure the bimodality of the excitation and to
      determine whether it could be reduced by using asymmetric pulses. Three types of
      maskers shapes were used: symmetric (SYM), pseudomonophasic (PS), and symmetric
      with a long inter-phase gap (SYM-IPG) pulses. Maskers were presented in BP + 9
      (wide), BP + 3 (narrow) and MP (only SYM) mode on fixed electrodes. The SOE
      obtained with the MP masker showed a main excitation peak close to the masker
      electrode. Wide SYM maskers produced bimodal excitation patterns showing two
      peaks close to the electrodes of the masker channel, whereas SYM-IPG maskers
      showed a single main peak near the electrode for which the masker's second phase
      (responsible for most of the masking) was anodic. Narrow SYM maskers showed
      complex and wider excitation patterns than asymmetric stimuli consistent with the
      overlap of the patterns produced by each channel's electrodes. The masking
      produced by narrow SYM-IPG and PS stimuli was more pronounced close to the masker
      electrode for which the effective phase was anodic. These results showed that the
      anodic polarity is the most effective one in BP mode and that the bimodal
      patterns produced by SYM maskers could be partially reduced by using asymmetric
      pulses.

PMID- 22583922
TI  - Hyperactivation of protein phosphatase 2A in models of glucolipotoxicity and
      diabetes: potential mechanisms and functional consequences.
AB  - The protein phosphatase 2A [PP2A] family of enzymes has been implicated in the
      regulation of a variety of cellular functions including hormone secretion,
      growth, survival and apoptosis. PP2A accounts for ~1% of total cellular protein
      and ~ 80% of total serine/threonine phosphatases, thus representing a major class
      of protein phosphatases in mammalian cells. Despite significant advances in our
      current understanding of regulation of cellular function by PP2A under
      physiological conditions, little is understood with regard to its regulation
      under various pathological conditions, such as diabetes. Emerging evidence
      suggests hyperactivation of PP2A in liver, muscle, retina and the pancreatic
      islet under the duress of glucolipotoxicity and diabetes. Interestingly,
      pharmacological inhibition of PP2A or siRNA-mediated depletion of the catalytic
      subunit of PP2A [PP2Ac] levels largely restored PP2A activity to near normal
      levels under these conditions. Herein, we provide an overview of PP2A subunit
      expression and activity in in vitro and in vivo models of glucolipotoxicity and
      diabetes, and revisit the existing data, which are suggestive of alterations in
      post-translational methylation, phosphorylation and nitration of PP2Ac under
      these conditions. Potential significance of hyperactive PP2A in the context of
      cell function, survival and apoptosis is also highlighted. It is hoped that this
      commentary will provide a basis for future studies to explore the potential for
      PP2Ac as a therapeutic target for the treatment of diabetes and other metabolic
      disorders.

PMID- 22583923
TI  - Effects of the natural flavone trimethylapigenin on cardiac potassium currents.
AB  - The natural flavones and polymethylflavone have been reported to have
      cardiovascular protective effects. In the present study, we determined whether
      quecertin, apigenin and their methylated compounds (3,7,3',4'
      tetramethylquecertin, 3,5,7,3',4'-pentamethylquecertin, 7,4'-dimethylapigenin,
      and 5,7,4'-trimethylapigenin) would block the atrial specific potassium channel
      hKv1.5 using a whole-cell patch voltage-clamp technique. We found that only
      trimethylapigenin showed a strong inhibitory effect on hKv1.5 channel current.
      This compound suppressed hKv1.5 current in HEK 293 cell line (IC50=6.4 MUM), and
      the ultra-rapid delayed rectify K+ current I(Kur) in human atrial myocytes
      (IC50=8.0 MUM) by binding to the open channels and showed a use- and frequency
      dependent manner. In addition, trimethylapigenin decreased transient outward
      potassium current (I(to)) in human atrial myocytes, inhibited acetylcholine
      activated K+ current (IC50=6.8MUM) in rat atrial myocytes. Interestingly,
      trimethylapigenin had a weak inhibition of hERG channel current. Our results
      indicate that trimethyapigenin significantly inhibits the atrial potassium
      currents hKv1.5/I(Kur) and I(KACh), which suggests that trimethylapigenin may be
      a potential candidate for anti-atrial fibrillation.

PMID- 22583924
TI  - Biomarker and dietary validation of a Canadian food frequency questionnaire to
      measure eicosapentaenoic and docosahexaenoic acid intakes from whole food,
      functional food, and nutraceutical sources.
AB  - BACKGROUND: Canadian dietary sources of eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) include marine and non-marine whole foods, functional
      foods, and nutraceuticals. OBJECTIVE/DESIGN: In the present study, these sources
      were incorporated into a nutrient-specific, semi-quantitative food frequency
      questionnaire (FFQ) and the ability to measure the EPA and DHA intakes of
      Canadian adults was assessed. Specifically, the EPA and DHA intakes estimated by
      FFQ of 78 men and women, 20 to 60 years of age, were compared with EPA and DHA
      measurements from 3-day food records and measures of EPA and DHA in fasting whole
      blood. RESULTS: Mean (+/-standard deviation) and median intakes of EPA+DHA were
      0.34+/-0.34 and 0.21 g/day by FFQ and 0.47+/-0.71 and 0.13 g/day by food record,
      with no significant differences between mean intakes (P=0.93). The FFQ provided
      higher estimates than the food record at low intakes of EPA and DHA and lower
      estimates at high intakes based on Bland-Altman plots. The FFQ was moderately
      correlated with food record (r=0.31 to 0.49) and with blood biomarker measures of
      EPA and DHA (r=0.31 to 0.51). Agreement analysis revealed that 42% of
      participants were classified in the same and 77% into same or adjacent quartile
      when EPA and DHA intake was assessed by food record and by FFQ. Similar quartile
      agreement was found for EPA and DHA intakes by FFQ with blood biomarker EPA and
      DHA. The range of the validity coefficients, calculated using the method of
      triads, was 0.43 to 0.71 for FFQ measurement of EPA+DHA. CONCLUSIONS: The FFQ is
      an adequate tool for estimating usual EPA and DHA intakes and ranking Canadian
      adults by their intakes.

PMID- 22583925
TI  - Efficacy of rosuvastatin for the treatment of non-alcoholic steatohepatitis with
      dyslipidemia: An open-label, pilot study.
AB  - AIM:   Statins, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)
      reductase, are reported to be useful for the treatment of non-alcoholic
      steatohepatitis (NASH). Currently, there is no proven therapy for NASH. In this
      study, we assessed the efficacy of rosuvastatin in NASH patients with
      dyslipidemia. METHODS:   Nineteen patients with biopsy-proven NASH with
      dyslipidemia who agreed to participate in this prospective study were enrolled.
      The patients were treated for 24 months with 2.5 mg/day rosuvastatin. Clinical
      and histological alterations were comparatively evaluated before and after
      treatment. Standard weight-loss counseling was continued during the treatment
      period. Follow-up liver biopsy was performed in nine patients. RESULTS:   Twenty
      six percent of patients had hyperlipoproteinemia type IIa and 74% had
      hyperlipoproteinemia type IIb at baseline. Body mass indices were not
      significantly changed during the treatment. The levels of transaminases were
      relatively low at the beginning, and were not significantly changed during the
      treatment. Lipid profiles were significantly improved by the treatment with
      rosuvastatin for 24 months. While non-alcoholic fatty liver disease activity
      score and fibrotic stage did not change significantly in all patients, they were
      improved in 33.3% and 33.3% individual patients, and stayed stable in 33.3% and
      55.6%, respectively. CONCLUSION:   NASH-related metabolic parameters improved
      with therapy including histology in some patients. However, one of nine patients
      had progression of fibrosis during the treatment. Our pilot study demonstrated
      the efficacy of rosuvastatin for the treatment of NASH with dyslipidemia, even if
      transaminases are not so elevated and controlled trials are needed in the future.

PMID- 22583926
TI  - [Unusual cause of unilateral deep vein thrombosis from urinary bladder].

PMID- 22583927
TI  - [Why meningococcal meningitis is still lethal: response in genes?].

PMID- 22583928
TI  - Allergen specificity of IgG(4)-expressing B cells in patients with grass pollen
      allergy undergoing immunotherapy.
AB  - BACKGROUND: Serum IgG(4) responses to allergen immunotherapy are well documented
      as blocking allergen binding to receptor-bound IgE on antigen-presenting cells
      and effector cells, but the molecular characteristics of treatment-induced
      IgG(4), particularly in relation to expressed antibody, are poorly defined.
      OBJECTIVES: We aimed to clone and express recombinant IgG(4) from patients
      receiving grass pollen immunotherapy using single B cells to obtain matched heavy
      and light-chain pairs. METHODS: IgG(4)(+) B cells were enriched from blood
      samples taken from 5 patients receiving grass pollen immunotherapy. Matched heavy
      and light-chain variable-region sequences were amplified from single IgG(4)(+) B
      cells. Variable regions were cloned and expressed as recombinant IgG(4). Binding
      analysis of grass pollen-specific IgG(4) was performed by using surface plasmon
      resonance. Functional assays were used to determine IgE blocking activity. In a
      separate experiment grass pollen-specific antibodies were depleted from serum
      samples to determine the proportion of grass pollen-specific IgG(4) within total
      IgG(4). RESULTS: Depletion of grass pollen-specific antibodies from serum led to
      a modest reduction in total IgG(4) levels. Matched heavy- and light-chain
      sequences were cloned from single IgG(4)(+) B cells and expressed as recombinant
      IgG(4). We identified an IgG(4) that binds with extremely high affinity to the
      grass pollen allergen Phl p 7. Furthermore, we found that a single specific mAb
      can block IgE-mediated facilitated allergen presentation, as well as IgE-mediated
      basophil activation. CONCLUSION: Although increases in IgG(4) levels cannot be
      wholly accounted for within the allergen-specific fraction, allergen
      immunotherapy might result in the production of high-affinity allergen-specific
      blocking IgG(4).

PMID- 22583929
TI  - Parasites and allergic disease: another piece of the puzzle.

PMID- 22583930
TI  - Is the Sexual Behaviour of HIV Patients on Antiretroviral therapy safe or risky
      in Sub-Saharan Africa? Meta-Analysis and Meta-Regression.
AB  - BACKGROUND: Reports on the sexual behavior of people on antiretroviral therapy
      (ART) are inconsistent. We selected 14 articles that compared the sexual behavior
      of people with and without ART for this analysis. METHODS: We included both cross
      sectional studies that compared different ART-naive and ART-experienced
      participants and longitudinal studies examining the behavior of the same
      individuals pre- and post-ART start. Meta-analyses were performed both stratified
      by type of study and combined. Outcome variables assessed for association with
      ART experience were any sexual activity, unprotected sex and having multiple
      sexual partners. Random-effect models were applied to determine the overall odds
      ratios. Sub-group analyses and meta-regression analyses were performed to examine
      sources of heterogeneity among the studies. Sensitivity analysis was also
      conducted to evaluate the stability of the overall odds ratio in the presence of
      outliers. RESULTS: The meta-analysis failed to show a statistically significant
      association of any sexual activity with ART experience. It did, however, show an
      overall statistically significant reduction of any unprotected sex, having
      multiple sexual partners and unprotected sex with HIV negative or unknown HIV
      status with ART experience. Meta-regression showed no interaction between
      duration of ART use or recall period of sexual behavior with the sexual activity
      variables. However, there was an association between the percentage of married or
      cohabiting participants included in a study and reductions in the practice of
      unprotected sex with ART. CONCLUSION: In general, this meta-analysis demonstrated
      a significant reduction in risky sexual behavior among people on ART in sub
      Saharan Africa. Future studies should investigate the reproducibility and
      continuity of the observed positive behavioural changes as the duration of ART
      lasts a decade or more.

PMID- 22583931
TI  - The isoflavone metabolite 6-methoxyequol inhibits angiogenesis and suppresses
      tumor growth.
AB  - BACKGROUND: Increased consumption of plant-based diets has been linked to the
      presence of certain phytochemicals, including polyphenols such as flavonoids.
      Several of these compounds exert their protective effect via inhibition of tumor
      angiogenesis. Identification of additional phytochemicals with potential
      antiangiogenic activity is important not only for understanding the mechanism of
      the preventive effect, but also for developing novel therapeutic interventions.
      RESULTS: In an attempt to identify phytochemicals contributing to the well
      documented preventive effect of plant-based diets on cancer incidence and
      mortality, we have screened a set of hitherto untested phytoestrogen metabolites
      concerning their anti-angiogenic effect, using endothelial cell proliferation as
      an end point. Here, we show that a novel phytoestrogen, 6-methoxyequol (6-ME),
      inhibited VEGF-induced proliferation of human umbilical vein endothelial cells
      (HUVE) cells, whereas VEGF-induced migration and survival of HUVE cells remained
      unaffected. In addition, 6-ME inhibited FGF-2-induced proliferation of bovine
      brain capillary endothelial (BBCE) cells. In line with its role in cell
      proliferation, 6-ME inhibited VEGF-induced phosphorylation of ERK1/2 MAPK, the
      key cascade responsible for VEGF-induced proliferation of endothelial cells. In
      this context, 6-ME inhibited in a dose dependent manner the phosphorylation of
      MEK1/2, the only known upstream activator of ERK1/2. 6-ME did not alter VEGF
      induced phosphorylation of p38 MAPK or AKT, compatible with the lack of effect on
      VEGF-induced migration and survival of endothelial cells. Peri-tumor injection of
      6-ME in A-431 xenograft tumors resulted in reduced tumor growth with suppressed
      neovasularization compared to vehicle controls (P < 0.01). CONCLUSIONS: 6-ME
      inhibits VEGF- and FGF2-induced proliferation of ECs by targeting the
      phosphorylation of MEK1/2 and it downstream substrate ERK1/2, both key components
      of the mitogenic MAPK pathway. Injection of 6-ME in mouse A-431 xenograft tumors
      results to tumors with decreased neovascularization and reduced tumor volume
      suggesting that 6-ME may be developed to a novel anti-angiogenic agent in cancer
      treatment.

PMID- 22583932
TI  - Identification of the up-regulation of TP-alpha, collagen alpha-1(VI) chain, and
      S100A9 in esophageal squamous cell carcinoma by a proteomic method.
AB  - Esophageal squamous cell carcinoma (ESCC) is one of the most common primary
      malignant tumor of digestive tract. However, the early diagnosis and molecular
      mechanisms that underlie tumor formation and progression have been progressed
      less. To identify new biomarkers for ESCC, we performed a comparative proteomic
      research. Isobaric tags for relative and absolute quantitation-based proteomic
      method was used to screen biomarkers between ESCC and normal. 802 non-redundant
      proteins were identified, 39 of which were differentially expressed with 1.5-fold
      difference (29 up-regulated and 10 down-regulated). Through Swiss-Prot and GO
      database, the location and function of differential proteins were analyzed, which
      are related to the biological processes of binding, cell structure, signal
      transduction, cell adhesion, etc. Among the differentially expressed proteins, TP
      alpha, collagen alpha-1(VI) chain and S100A9 were verified to be upregulated in
      77.19%, 75.44% and 59.65% of ESCC by immunohistochemistry and western-blot.
      Diagnostic value of these three proteins was validated. These results provide new
      insights into ESCC biology and potential diagnostic and therapeutic biomarkers,
      which suggest that TP-alpha, collagen alpha-1(VI) chain and S100A9 are potential
      biomarkers of ESCC, and may play an important role in tumorigenesis and
      development of ESCC.

PMID- 22583933
TI  - Saliva proteomics as an emerging, non-invasive tool to study livestock
      physiology, nutrition and diseases.
AB  - Saliva is an extraordinary fluid in terms of research and diagnostic
      possibilities. Its composition in electrolytes, hormones and especially its
      proteome contains information about feeding status, nutritional requirements and
      adaptations to diet and environment, and also about health status of animals. It
      is easy to collect on a non-invasive and routine basis without any need for
      special training. Therefore, the analysis of salivary proteomes is going to
      emerge into a field of high interest with the future goal to maintain and improve
      livestock productivity and welfare. Moreover, the comprehensive analysis and
      identification of salivary proteins and peptides in whole and glandular saliva is
      a necessary pre-requisite to identify animal disease biomarkers and a powerful
      tool to better understand animal physiology. This review focuses on the different
      approaches used to study the salivary proteomes of farm animals, in respect to
      the physiology of nutrition and food perception in relation to food choices. The
      potential of animal saliva as a source of disease biomarkers will also be pointed
      out. Special emphasis is laid on the 'ruminating triad' - cattle, goat and sheep 
      as well as swine as major species of animal production in Western and Southern
      Europe.

PMID- 22583935
TI  - Turkish nurses' level of knowledge regarding implantable port catheter care.
AB  - AIM: The aim of this study was to determine the knowledge levels of Turkish
      nurses regarding implantable port catheter care. METHODS: A descriptive method
      was used inside a university hospital that was located in a Turkish metropolis.
      The data were collected via a questionnaire that was given to a total of 45
      nurses who were employed in the internal medicine clinics where the oncology
      patients were treated. RESULTS: In this study, 42.2% of the nurses received in
      service training about the implantable port catheter. It was determined that the
      mean knowledge point was 15.13 +/- 4.78. The difference between the knowledge
      points of the nurses regarding implantable port catheter care, based on whether
      or not the nurses had received in-service training, was statistically
      significant. Moreover, it was determined that the majority of the nurses did not
      know where the implantable port catheter is placed, its period of use following
      implantation, the amount of normal saline to be used for washing the catheter,
      the special port (Huber) needle, the number of the needle, and the exchange time
      of these needles. CONCLUSION: In this study, there existed significant
      differences between the scores of the nurses who received in-service training
      about the implantable port catheter and the scores of those who did not receive
      in-service training. The majority of the nurses who participated in the study
      were willing to receive in-service training regarding this subject. Thus, the
      organization of in-service training programs and the implementation of care,
      according to the developed standards and guidelines, are considered as
      significant for reducing the occurrence of the complications that are related to
      the use of the implantable port catheter.

PMID- 22583934
TI  - Urinary calculi and an increased risk of stroke: a population-based follow-up
      study.
AB  - Study Type--Prognosis (cohort) Level of Evidence 2b. What's known on the subject?
      and What does the study add? Although early studies failed to detect an
      association between urinary calculi (UC) and subsequent cardiovascular risk,
      there is growing evidence among more recent research supporting this association
      with some studies more specifically suggesting that stroke is a major concern for
      UC sufferers. After adjusting for potential confounding factors, UC patients were
      more likely to have experienced a stroke then those without UC during the five
      year follow-up period (hazard ratio = 1.43, 95% Cl = 1.35-1.50, P < 0.001).
      OBJECTIVE: * To examine in a population-based study the relationship between a
      history of nephrolithiasis and/or ureterolithiasis and the subsequent risk of
      stroke, as previous studies have shown that stone disease is associated with
      several cardiovascular risk factors. However, none of the studies that have
      investigated the relationship between urinary calculi (UC) and stroke were able
      to detect an association at a significant level. PATIENTS AND METHODS: * We used
      data sourced from the Taiwan Longitudinal Health Insurance Database 2000. * In
      all, 25,181 adult patients newly diagnosed with UC were recruited as a study
      cohort, along with 125,905 matched enrolees with no history of stone disease as a
      comparison cohort. * All the subjects were tracked for a 5-year period beginning
      from their index ambulatory care visits, and those who subsequently had a stroke
      identified. * Cox proportional hazards regressions were used to compare the risk
      of stroke between the study and comparison cohorts. RESULTS: * During the 5-year
      follow-up period, the incidence rate of stroke was 1.78 (95% confidence interval
      [CI] 1.71-1.86) per 100 person-years in patients with UC and 1.25 (95% CI 1.22
      1.27) per 100 person-years in patients without UC. * After adjusting for
      hypertension, diabetes, hyperlipidaemia, cardiovascular disease, urbanization
      level, gout, and obesity, patients with UC were more likely to have had a stroke
      than those without UC during the 5-year follow-up period (hazard ratio 1.43, 95%
      CI 1.35-1.50, P < 0.001). CONCLUSION: * Our results suggest that there is an
      increased risk of stroke during the first 5 years after a diagnosis of UC.

PMID- 22583936
TI  - Experiences of a critical reflection program for mid-career nurses.
AB  - AIM: The aim of the present study was to describe the experiences of Japanese
      nurses who participated in a critical reflection program for mid-career nurses.
      Critical reflection is one method that is appropriate for the professional
      development of mid-career nurses. However, its implementation is difficult
      because of the need for educational resources. Of the numerous reports on
      critical reflection outcomes, few delineate the underlying process and none
      relates to Japanese nurses. METHODS: A program was developed, based on Mezirow's
      transformation theory, to facilitate nurses' critical reflection. The program was
      implemented at three hospitals in Japan with 14 mid-career nurses. The data
      collection period was from 2006 to 2007. The grounded theory approach was used to
      describe the results. RESULTS: Two participants experienced a transformation in
      their frame of reference after undergoing critical reflection during the program.
      One participant's viewpoint began to change and the other's "habit of mind"
      (social norms and personality characteristics that provide one with a general
      orientation) changed. Both participants met the conditions that were necessary
      for transformation, such as having an open attitude toward change, and compared
      to the other participants, their critical reflection progressed markedly on the
      worksheets that were designed to promote critical reflection. The process of
      change in the frame of reference that was experienced by the two participants
      followed eight of the ten phases of Mezirow's transformation theory. CONCLUSIONS:
      The characteristics of the experiences of the two participants who underwent
      changes in their frame of reference were described and discussed. The conditions
      for such transformation and the effects of critical reflection on the
      participants were consistent with those reported by previous studies.

PMID- 22583937
TI  - Use of complementary and alternative medicine and the anxiety levels of mothers
      of children with chronic diseases.
AB  - AIMS: This study aimed to determine the use of complementary and alternative
      medicine (CAM) by mothers with a chronically ill child and their anxiety levels.
      METHODS: This study used a descriptive design. The study was conducted with 135
      mothers of a chronically ill child at a general pediatric and oncology unit in
      Uludag University Hospital, Bursa, Turkey. A questionnaire, including
      sociodemographic items and the State-Trait Anxiety Inventory, were given to the
      mothers. RESULTS: In the study, 42.29% of the mothers reported using one or more
      CAM therapies for their child with a chronic disease, including herbal medicine,
      taking the child to hodja (prayers), a special diet, and a special massage. The
      mothers experienced anxiety and the presence of a disease within the close family
      circle increased the anxiety level of the mothers. CONCLUSION: Herbs and other
      alternative supplements were used by some children with a chronic disease in
      Turkey. The most commonly used CAM therapies included oral herbal medicine,
      taking the child to hodja, massage, and diets. Therefore, it is important to
      consider the implications of the popularity of complementary therapies. Most of
      the mothers used more than one of these therapies for their child and the anxiety
      level of the mothers was found to be moderate.

PMID- 22583938
TI  - Adverse effects and appetite suppression associated with particle beam therapy in
      patients with head and neck cancer.
AB  - AIM: This purpose of this study was to investigate the relationship between the
      appetite and various factors that are associated with particle beam therapy,
      including the adverse effects of radiation, dry-mouth period, analgesic
      medication use, frequency of oral care, and participants' characteristics, in 121
      patients with head and neck cancer. METHODS: A path analysis was used to evaluate
      the causal relationship of the factors that affected the participants' appetite.
      RESULTS: At a cumulative dose of 40 GyE, the factors that impacted the
      participants' appetite included xerostomia, oral mucositis, age, frequency of
      oral care, and analgesic medication use. At a cumulative dose of 50 GyE, the
      factors that affected the participants' appetite were xerostomia, sensitivity to
      taste, oral mucositis, dry-mouth period (in the morning), frequency of oral care,
      number of artificial teeth, and analgesic medication use. The results indicate
      that interventions to avoid appetite suppression during particle beam therapy
      will differ according to a radiation schedule of 40 GyE, compared to 50 GyE.
      CONCLUSIONS: These results are important to consider when deciding how best to
      maintain the dietary intake of patients who are receiving particle beam therapy.

PMID- 22583939
TI  - Factors involved in the feelings related to school avoidance among high school
      students in Nagano Prefecture, Japan.
AB  - AIM: The present study aimed to identify the factors that are involved in the
      feelings related to school avoidance of high school students in order to develop
      a support method and a strategy for preventing school maladjustment. METHOD: A
      total of 1756 students from three public high schools in Nagano Prefecture in
      Japan agreed to participate in the study. They were asked to complete the
      Feelings of School Avoidance (FSA) Scale, as well as information relating to
      their demographic details, living environment, lifestyle, and psychosocial
      factors. RESULTS: Valid responses were obtained from 1178 students. The mean
      scores of all three subscales of the FSA Scale increased with the students'
      grade. In the hierarchical multiple linear regression analysis, the students'
      age, family size, and social support were excluded from the predictors and the
      anthropophobic tendency and social skills were analyzed separately in order to
      avoid multicollinearity. When the anthropophobic tendency was included, the
      students' grade, anthropophobic tendency, self-esteem, and support by school
      friends were significant predictors for all the FSA subscales. When the level of
      social skills was included instead of the anthropophobic tendency, the analysis
      yielded similar results, except that the students' social skills and unidentified
      complaints were selected instead of the anthropophobic tendency. CONCLUSION:
      Among the high school students, the anthropophobic tendency contributed to their
      feelings related to school avoidance most strongly. These results suggest the
      necessity of understanding students' anthropophobic tendency in detail,
      developing effective support in order to promote their social skills and self
      esteem, and helping them to make friends, as well as improving their human
      relationships in order to prevent school maladjustment.

PMID- 22583940
TI  - Physiological and psychological responses induced by expressing empathy with
      others.
AB  - AIM: To assess the physical and mental burdens associated with expressing empathy
      with another person's stress. METHODS: Nine female subjects listened to their
      partner's negative emotions aroused by a stress task (Stroop color-word test)
      under two conditions. In the first, the subject reacted empathetically to their
      partner ("with empathy"); in the second, the subject offered no response
      (control). Electroencephalograms and skin temperature of the second finger were
      recorded during the test. Subjective stress was estimated using a visual analog
      scale, whereas the level of cognition was expressed on a five-point ranking.
      Responses during and after expressions of empathy were examined by comparisons
      with control or by correlation. RESULTS: Sympathetic nerve tone increased under
      both conditions (i.e. the skin temperature of the second finger fell). Subjective
      stress was not recognized by the subject while listening "with empathy", although
      it did increase significantly after the subject has listened "with empathy".
      Subjective stress was not felt under the control conditions. Right temporal
      activity while listening showed a significantly positive correlation with the
      level of cognition of feeling the same emotion as the stressed partner, whereas
      bilateral frontal activity after listening was significantly negative correlated
      with the level of cognition of understanding the emotions of the stressed
      partner. CONCLUSION: Expressing empathy with another person's negative emotion
      led to increased physiological activity and subjective stress. Physiological
      responses to empathy depended on cognition of the different subjective factors.
      Cognition of sharing negative emotions activated the right temporal region of the
      brain, whereas cognition of understanding negative emotions inhibited bilateral
      frontal activities.

PMID- 22583941
TI  - Turnover intention of graduate nurses in South Korea.
AB  - AIM: The purpose of this study was to identify the turnover intention of graduate
      nurses in South Korea and to explore the correlates of turnover intention.
      METHODS: A descriptive, correlational design was used. The participants comprised
      225 female nurses who were working at 13 general hospitals and who had
      accumulated <12 months of clinical nursing experience since their graduation. The
      data were collected through a structured questionnaire that was conducted from 5
      31 August 2009. RESULTS: The mean score for turnover intention was 7.51. Turnover
      intention was found to be related to the number of beds in the hospital,
      workplace, and duration of job orientation (theory and practice), instruction by
      a preceptor, job stress, clinical competence, self-efficacy, and the practice
      environment. In the multivariate approach, the practice environment, job stress,
      and the workplace were found to be significantly related to turnover intention
      and accounted for 36% of the said intention in the studied graduate nurses.
      CONCLUSION: The results support that the characteristics of magnet hospitals that
      improve the practice environment could play a critical role in retaining nurses
      in hospitals. Managerial interventions that enhance the practice environment,
      reduce job stress, and place graduate nurses in nursing units with a single
      specialty could benefit the hospitals employing such nurses. Further research to
      explore the effects of managerial strategies on graduate nurses' turnover
      intention is warranted.

PMID- 22583942
TI  - Effectiveness of the "Elevated Position" Nursing Care Program in promoting the
      reconditioning of patients with acute cerebrovascular disease.
AB  - AIM: Over 34,000 Japanese patients suffer from a persistent disturbance of
      consciousness. The purpose of this study was to investigate the effectiveness of
      the "Elevated Position" Nursing Care Program (EPNCP) in promoting the
      reconditioning of patients with acute cerebrovascular disease (ACD). The primary
      assumption of this study was that they could experience the reconditioning
      process and would reach a reconditioned state through their involvement in the
      EPNCP, thus improving their level of consciousness and quality of life. METHOD: A
      historical controlled trial study, based on an intention-to-treat analysis of
      hospitalized patients with ACD who became participants the day after starting
      medical or surgical treatment, was used. Trained nurses implemented the EPNCP
      from May to September 2005 for an experimental group of 45 participants. The data
      on two independent control groups of 92 and 40 patients with ACD were gathered
      from historical medical records. The six measures were: Japan Coma Scale; Level
      of Cognitive Functioning Assessment Scale; number of days from the intervention
      to sitting in a wheelchair; number of participants who left the intensive care
      unit (ICU) by wheelchair; Barthel Index; and modified Rankin Scale. RESULTS:
      Significant differences were found regarding the number of participants who left
      the ICU by wheelchair, length of time from the EPNCP's commencement to the
      wheelchair-sitting position, and the Barthel Index 1 week after leaving the ICU.
      CONCLUSION: The EPNCP was safe for the reconditioning of patients with ACD and
      somewhat effective in improving their physical function. A comprehensive nursing
      care program now exists for elevating patients with cerebrovascular disease
      during the early phase following the onset of symptoms or immediately after
      surgery. Further research should be conducted, extending the duration of the
      intervention program and the length of the measurement period, followed by a
      careful analysis of the results.

PMID- 22583943
TI  - Development of the inpatient attitudes towards the patient role scale.
AB  - AIM: The purpose of this study was to develop a reliable, valid scale that can
      measure inpatients' tendencies and level of effort in dealing with their role of
      patient. METHODS: The question items were developed from interviews and a review
      of the literature. After examining the content validity, a pretest and pilot
      study were conducted. Then, the 27 item Inpatient Attitudes Towards the Patient
      Role Scale was created. A self-administered questionnaire survey with 399
      inpatients was conducted in order to examine the reliability and validity of this
      scale. RESULTS: Two-hundred-and-sixteen patients completed and returned the
      questionnaire (54.1% response rate). The respondents were aged between 20 years
      and >=80 years (median: 60s); 60% were male and 39% were female. Based on a
      factor analysis, the following four common factors were extracted from 21 out of
      the 27 original items: "patient adherence", "consideration", "self-expression",
      and "mental attitude". The evidence from an examination of the construct validity
      and stability suggests that the scale has good reliability and promising
      validity. Older adult patients tended to make more effort than younger patients.
      The patients who believed that it would take them a certain amount of time to
      recover and those who trusted the healthcare staff tended to make more effort.
      CONCLUSION: A reliable and valid scale to measure inpatient attitudes towards the
      patient role was developed. This scale might provide useful information for
      nursing practice.

PMID- 22583944
TI  - Attitudes of Korean adults towards human dignity: a Q methodology approach.
AB  - AIM: The aim of this study was to identify the perceived attitudes of Korean
      adults towards human dignity in order to determine the relationship of human
      dignity to its social and cultural background. METHODS: The Q methodology
      research technique was used to explore perceived attitude typology on the basis
      of the respondents' ranking order for different statements. A convenience
      sampling method was used to select 40 Korean adults who were interested in human
      dignity to create statements. From the questionnaires, in-depth interviews, and a
      literature review, a total of 158 statements was obtained. The final 34 Q samples
      were selected from a review by two nursing professors and a Q methodology expert.
      Moreover, 38 respondents participated as P samples by sorting 34 Q statements on
      a nine-point normal distribution scale. The data were analyzed by using the QUANL
      software package. RESULTS: The following four types of attitudes about human
      dignity were identified in Korea: a happiness-oriented-self-pursuit type,
      relationship-oriented-self-recognition type, reflection-oriented-self-unification
      type, and discrimination-oriented-self-maintenance type. CONCLUSIONS: The results
      indicate that approaches to developing human dignity education need to take this
      typology into account and the characteristics of the participants who fall into
      each category. These results provide general guidelines to understand Korean
      values for professional practice in various healthcare settings.

PMID- 22583945
TI  - Working conditions associated with ovarian cycle in a medical center nurses: a
      Taiwan study.
AB  - AIM: Decreased basal body temperature measurements predict ovulation with an
      accuracy of 74%. The anovulatory cycle exhibits an ovarian monophasic pattern.
      This study evaluated the relationship between ovarian cycle pattern and
      sociodemographic characteristics, menstrual history and work characteristics of
      nurses in a Taiwan medical center. METHODS: Of 200 nurses recruited, 151 were
      analyzed. Each subject completed questionnaires and provided life recordings and
      daily basal body temperature measurements during the 14-week study. RESULTS: The
      analytical results demonstrated that work place (P = 0.014) and work shift (P =
      0.048) are significantly related to ovarian cycle pattern. Nurses who worked in
      emergent care units and wards had a higher prevalence of irregular ovarian cycle
      pattern. Approximately 53% of nurses who worked rotating shifts exhibited
      irregular ovarian cycle pattern. CONCLUSIONS: Nurses who either had rotating
      shift work or worked in emergent care units and wards should be concerned with
      their own ovarian cycle pattern for their health.

PMID- 22583946
TI  - Serum insulin-like growth factor-I (IGF-I) reference ranges for chemiluminescence
      assay in childhood and adolescence. Data from a population of in- and out
      patients.
AB  - BACKGROUND: Insulin-like growth factor I (IGF-I) measurement is widely used for
      the diagnosis of disorders of GH secretion and sensitivity, and for monitoring of
      both GH and IGF-I replacement therapies. However, the lack of appropriate
      reference values obtained from large and representative samples undermines its
      practical utility. OBJECTIVE: To establish IGF-I reference values for a commonly
      used enzyme-labeled chemiluminescent immunometric assay in a large population of
      children aged 0 to 18 years. DESIGN: Cross-sectional analysis of serum IGF-I
      levels from samples collected in the two major Italian Children's Hospitals.
      SUBJECTS AND METHODS: IGF-I was measured using a solid-phase, enzyme-labeled
      chemiluminescent immunometric assay in 24403 children (50.6% girls) aged 0 to 18
      years. Quantile regression coupled to multivariable fractional polynomials was
      used to produce age- and sex-specific reference values. MAIN OUTCOME MEASURE: Age
      and sex-specific IGF-I reference values. RESULTS AND CONCLUSION: Reference
      values for immunometric assay of IGF-I were produced in a large sample of
      children and adolescents. Prediction equations were provided to automatize their
      calculations.

PMID- 22583947
TI  - Growth cartilage expression of growth hormone/insulin-like growth factor I axis
      in spontaneous and growth hormone induced catch-up growth.
AB  - INTRODUCTION: Catch-up growth following the cessation of a growth inhibiting
      cause occurs in humans and animals. Although its underlying regulatory mechanisms
      are not well understood, current hypothesis confer an increasing importance to
      local factors intrinsic to the long bones' growth plate (GP). AIM: The present
      study was designed to analyze the growth-hormone (GH)-insulin-like growth factor
      I (IGF-I) axis in the epiphyseal cartilage of young rats exhibiting catch-up
      growth as well as to evaluate the effect of GH treatment on this process.
      MATERIAL AND METHODS: Female Sprague-Dawley rats were randomly grouped: controls
      (group C), 50% diet restriction for 3 days+refeeding (group CR); 50% diet
      restriction for 3 days+refeeding & GH treatment (group CRGH). Analysis of GH
      receptor (GHR), IGF-I, IGF-I receptor (IGF-IR) and IGF binding protein 5 (IGFBP5)
      expressions by real-time PCR was performed in tibial growth plates extracted at
      the time of catch-up growth, identified by osseous front advance greater than
      that of C animals. RESULTS: In the absence of GH treatment, catch-up growth was
      associated with increased IGF-I and IGFBP5 mRNA levels, without changes in GHR or
      IGF-IR. GH treatment maintained the overexpression of IGF-I mRNA and induced an
      important increase in IGF-IR expression. CONCLUSIONS: Catch-up growth that
      happens after diet restriction might be related with a dual stimulating local
      effect of IGF-I in growth plate resulting from overexpression and increased
      bioavailability of IGF-I. GH treatment further enhanced expression of IGF-IR
      which likely resulted in a potentiation of local IGF-I actions. These findings
      point out to an important role of growth cartilage GH/IGF-I axis regulation in a
      rat model of catch-up growth.

PMID- 22583948
TI  - Fetal rat metabonome alteration by prenatal caffeine ingestion probably due to
      the increased circulatory glucocorticoid level and altered peripheral glucose and
      lipid metabolic pathways.
AB  - The aims of this study were to clarify the metabonome alteration in fetal rats
      after prenatal caffeine ingestion and to explore the underlying mechanism
      pertaining to the increased fetal circulatory glucocorticoid (GC). Pregnant
      Wistar rats were daily intragastrically administered with different doses of
      caffeine (0, 20, 60 and 180 mg/kg) from gestational days (GD) 11 to 20.
      Metabonome of fetal plasma and amniotic fluid on GD20 were analyzed by 1H nuclear
      magnetic resonance-based metabonomics. Gene and protein expressions involved in
      the GC metabolism, glucose and lipid metabolic pathways in fetal liver and
      gastrocnemius were measured by real-time RT-PCR and immunohistochemistry. Fetal
      plasma metabonome were significantly altered by caffeine, which presents as the
      elevated alpha- and beta-glucose, reduced multiple lipid contents, varied
      apolipoprotein contents and increased levels of a number of amino acids. The
      metabonome of amniotic fluids showed a similar change as that in fetal plasma.
      Furthermore, the expressions of 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD
      2) were decreased, while the level of blood GC and the expressions of 11beta-HSD
      1 and glucocorticoid receptor (GR) were increased in fetal liver and
      gastrocnemius. Meanwhile, the expressions of insulin-like growth factor 1 (IGF
      1), IGF-1 receptor and insulin receptor were decreased, while the expressions of
      adiponectin receptor 2, leptin receptors and AMP-activated protein kinase alpha2
      were increased after caffeine treatment. Prenatal caffeine ingestion
      characteristically change the fetal metabonome, which is probably attributed to
      the alterations of glucose and lipid metabolic pathways induced by increased
      circulatory GC, activated GC metabolism and enhanced GR expression in peripheral
      metabolic tissues.

PMID- 22583950
TI  - An exploratory study into the role of dynamic contrast-enhanced (DCE) MRI metrics
      as predictors of response in head and neck cancers.
AB  - AIM: To assess the efficacy of dynamic contrast-enhanced magnetic resonance
      imaging (DCE MRI) in prediction of the response to treatment in patients with
      head and neck cancers (HNCs). METHODS AND MATERIALS: Twenty-one patients with
      advanced HNC, suitable for concurrent chemoradiotherapy underwent DCE MRI, for
      the quantification of blood flow (BF) and volume (BV). All the patients received
      radical doses of conventionally fractionated radiotherapy up to a dose of 70 Gy
      along with concurrent weekly cisplatin. RESULTS: The values of BV and BF were
      higher in complete responders as compared to partial responders at primary as
      well as nodes. Both BF and BV were found to be significantly higher in patients
      with high T-stage as compared to patients with lower T-stage. CONCLUSIONS: DCE
      metrics can be used as a predictor of response to treatment in locally advanced
      HNCs after validation of these observations in a larger number of patients.

PMID- 22583949
TI  - Neuregulin-1 is neuroprotective in a rat model of organophosphate-induced delayed
      neuronal injury.
AB  - Current medical countermeasures against organophosphate (OP) nerve agents are
      effective in reducing mortality, but do not sufficiently protect the CNS from
      delayed brain damage and persistent neurological symptoms. In this study, we
      examined the efficacy of neuregulin-1 (NRG-1) in protecting against delayed
      neuronal cell death following acute intoxication with the OP
      diisopropylflurophosphate (DFP). Adult male Sprague-Dawley rats were pretreated
      with pyridostigmine (0.1 mg/kg BW, i.m.) and atropine methylnitrate (20 mg/kg BW,
      i.m.) prior to DFP (9 mg/kg BW, i.p.) intoxication to increase survival and
      reduce peripheral signs of cholinergic toxicity but not prevent DFP-induced
      seizures or delayed neuronal injury. Pretreatment with NRG-1 did not protect
      against seizures in rats exposed to DFP. However, neuronal injury was
      significantly reduced in most brain regions by pretreatment with NRG-1 isoforms
      NRG-EGF (3.2 MUg/kg BW, i.a) or NRG-GGF2 (48 MUg/kg BW, i.a.) as determined by
      FluroJade-B labeling in multiple brain regions at 24 h post-DFP injection. NRG-1
      also blocked apoptosis and oxidative stress-mediated protein damage in the brains
      of DFP-intoxicated rats. Administration of NRG-1 at 1h after DFP injection
      similarly provided significant neuroprotection against delayed neuronal injury.
      These findings identify NRG-1 as a promising adjuvant therapy to current medical
      countermeasures for enhancing neuroprotection against acute OP intoxication.

PMID- 22583951
TI  - Complications after percutaneous placement of totally implantable venous access
      ports in the forearm.
AB  - This article focuses on radiological imaging of complications after
      interventional percutaneous insertion of totally implantable venous access ports
      (TIVAPs) which were placed in the forearm. Thus far most reviews have dealt with
      pectorally-placed TIVAPs. Compared with the pectoral approach, implantation in
      the forearm has been associated with certain complications owing to a longer
      route of the port catheter within a smaller vein, and owing to the route across
      the elbow joint, resulting in higher rates of catheter-associated thrombosis and
      possible mechanical complications. The purpose of this review is to describe the
      complications after implantation of TIVAPs in the forearm, and to make
      radiologists familiar with the key findings of the complications during
      radiological imaging, including colour-coded and compression Duplex ultrasound,
      computed tomography, and digital subtraction venography.

PMID- 22583952
TI  - DelPhi: a comprehensive suite for DelPhi software and associated resources.
AB  - BACKGROUND: Accurate modeling of electrostatic potential and corresponding
      energies becomes increasingly important for understanding properties of
      biological macromolecules and their complexes. However, this is not an easy task
      due to the irregular shape of biological entities and the presence of water and
      mobile ions. RESULTS: Here we report a comprehensive suite for the well-known
      Poisson-Boltzmann solver, DelPhi, enriched with additional features to facilitate
      DelPhi usage. The suite allows for easy download of both DelPhi executable files
      and source code along with a makefile for local installations. The users can
      obtain the DelPhi manual and parameter files required for the corresponding
      investigation. Non-experienced researchers can download examples containing all
      necessary data to carry out DelPhi runs on a set of selected examples
      illustrating various DelPhi features and demonstrating DelPhi's accuracy against
      analytical solutions. CONCLUSIONS: DelPhi suite offers not only the DelPhi
      executable and sources files, examples and parameter files, but also provides
      links to third party developed resources either utilizing DelPhi or providing
      plugins for DelPhi. In addition, the users and developers are offered a forum to
      share ideas, resolve issues, report bugs and seek help with respect to the DelPhi
      package. The resource is available free of charge for academic users from URL:
      http://compbio.clemson.edu/DelPhi.php.

PMID- 22583953
TI  - Corynebacterium ulcerans 0102 carries the gene encoding diphtheria toxin on a
      prophage different from the C. diphtheriae NCTC 13129 prophage.
AB  - BACKGROUND: Corynebacterium ulcerans can cause a diphtheria-like illness,
      especially when the bacterium is lysogenized with a tox gene-carrying
      bacteriophage that produces diphtheria toxin. Acquisition of toxigenicity upon
      phage lysogenization is a common feature of C. ulcerans and C. diphtheriae.
      However, because of a lack of C. ulcerans genome information, a detailed
      comparison of prophages has not been possible between these two clinically
      important and closely related bacterial species. RESULTS: We determined the whole
      genome sequence of the toxigenic C. ulcerans 0102 isolated in Japan. The genomic
      sequence showed a striking similarity with that of Corynebacterium
      pseudotuberculosis and, to a lesser extent, with that of C. diphtheriae. The 0102
      genome contained three distinct prophages. One of these, PhiCULC0102-I, was a tox
      positive prophage containing genes in the same structural order as for tox
      positive C. diphtheriae prophages. However, the primary structures of the
      individual genes involved in the phage machinery showed little homology between
      the two counterparts. CONCLUSION: Taken together, these results suggest that the
      tox-positive prophage in this strain of C. ulcerans has a distinct origin from
      that of C. diphtheriae NCTC 13129.

PMID- 22583954
TI  - Brain rust: recent discoveries on the role of oxidative stress in
      neurodegenerative diseases.
AB  - Oxidative stress (OS) and damages due to excessive reactive oxygen species (ROS)
      are common causes of injuries to cells and organisms. The prevalence of
      neurodegenerative diseases (ND) increases with aging and much of the research
      involving ROS and OS has emerged from works in this  field. This text reviews
      some recent published articles about the role of OS in ND. Since there are many
      reviews in this field, the focus was centered in articles published recently. The
      Scientific Journals Directory supported by the Brazilian Ministry of Education
      Office for the Coordination  of Higher Educational Personnel Improvement (CAPES)
      was used to search, download, and review articles. The search engine looked for
      the terms 'oxidative stress AND neurodegenerative diseases AND nutrition' in 10
      different scientific collections. Biochemical markers for ND lack  sensitivity or
      specificity for diagnosis or for tracking response to therapy today. OS has an
      intimate connection with ND, albeit low levels of ROS seem to protect the brain.
      Deleterious changes in mitochondria, OS, calcium, glucocorticoids, inflammation,
      trace metals, insulin, cell cycle,  protein aggregation, and hundreds to
      thousands of genes occur in ND. The interaction of genes with their environment,
      may explain ND. Although OS has received much attention over the years, which
      increased the number of scientific works on antioxidant interventions, no one
      knows how to stop  or delay ND at present. Interventions in vitro, in vivo, and
      in humans will continue to contribute for a better understanding of these
      pathologies.

PMID- 22583955
TI  - Event-related potential examination of facial affect processing in bipolar
      disorder and schizophrenia.
AB  - BACKGROUND: Patients with bipolar disorder exhibit consistent deficits in facial
      affect identification at both behavioral and neural levels. However, little is
      known about which stages of facial affect processing are dysfunctional. METHOD:
      Event-related potentials (ERPs), including amplitude and latency, were used to
      evaluate two stages of facial affect processing: N170 to examine structural
      encoding of facial features and N250 to examine decoding of facial features in 57
      bipolar disorder patients, 30 schizophrenia patients and 30 healthy controls.
      Three conditions were administered: participants were asked to identify the
      emotion of a face, the gender of a face, or whether a building was one or two
      stories tall. RESULTS: Schizophrenia patients' emotion identification accuracy
      was lower than that of bipolar patients and healthy controls. N170 amplitude was
      significantly smaller in schizophrenia patients compared to bipolar patients and
      healthy controls, which did not differ from each other. Both patient groups had
      significantly longer N170 latency compared to healthy controls. For N250, both
      patient groups showed significantly smaller amplitudes compared with controls,
      but did not differ from each other. Bipolar patients showed longer N250 latency
      than healthy controls; patient groups did not differ from each other.
      CONCLUSIONS: Bipolar disorder patients have relatively intact structural encoding
      of faces (N170) but are impaired when decoding facial features for complex
      judgments about faces (N250 latency and amplitude), such as identifying emotion
      or gender.

PMID- 22583956
TI  - Eye movement responses to health messages on cigarette packages.
AB  - BACKGROUND: While the majority of the health messages on cigarette packages
      contain threatening health information, previous studies indicate that risk
      information can trigger defensive reactions, especially when the information is
      self-relevant (i.e., smokers). Providing coping information, information that
      provides help for quitting smoking, might increase attention to health messages
      instead of triggering defensive reactions. METHODS: Eye-movement registration can
      detect attention preferences for different health education messages over a
      longer period of time during message exposure. In a randomized, experimental
      study with 23 smoking and 41 non-smoking student volunteers, eye-movements were
      recorded for sixteen self-created cigarette packages containing health texts that
      presented either high risk or coping information combined with a high threat or a
      low threat smoking-related photo. RESULTS: Results of the eye movement data
      showed that smokers tend to spend more time looking (i.e., more unique fixations
      and longer dwell time) at the coping information than at the high risk
      information irrespective of the content of the smoking-related photo. Non-smokers
      tend to spend more time looking at the high risk information than at the coping
      information when the information was presented in combination with a high threat
      smoking photo. When a low threat photo was presented, non-smokers paid more
      attention to the coping information than to the high risk information. Results
      for the smoking photos showed more attention allocation for low threat photos
      that were presented in combination with high risk information than for low threat
      photos in combination with coping information. No attention differences were
      found for the high threat photos. CONCLUSIONS: Non-smokers demonstrated an
      attention preference for high risk information as opposed to coping information,
      but only when text information was presented in combination with a high threat
      photo. For smokers, however, our findings suggest more attention allocation for
      coping information than for health risk information. This preference for coping
      information is not reflected in current health messages to motivate smokers to
      quit smoking. Coping information should be more frequently implemented in health
      message design to increase attention for these messages and thus contribute to
      effective persuasion.

PMID- 22583957
TI  - High dose methylphenidate treatment in adult attention deficit hyperactivity
      disorder: a case report.
AB  - INTRODUCTION: Stimulant medication improves hyperactivity, inattention, and
      impulsivity in both pediatric and adult populations with Attention Deficit
      Hyperactivity Disorder (ADHD). However, data regarding the optimal dosage in
      adults is still limited. CASE PRESENTATION: We report the case of a 38-year-old
      Caucasian patient who was diagnosed with Attention Deficit Hyperactivity Disorder
      when he was nine years old. He then received up to 10 mg methylphenidate
      (Ritalin(r)) and 20 mg sustained-release methylphenidate (Ritalin SR(r)) daily.
      When he was 13, his medication was changed to desipramine (Norpramin(r)), and
      both Ritalin(r) and Ritalin SR(r) were discontinued; and at age 18, when he
      developed obsessive-compulsive symptoms, his medication was changed to
      clomipramine (Anafranil(r)) 75 mg daily. Still suffering from inattention and
      hyperactivity, the patient began college when he was 19, but did not receive
      stimulant medication until three years later, when Ritalin(r) 60 mg daily was re
      established. During the 14 months that followed, he began to use Ritalin(r)
      excessively, both orally and rectally, in dosages from 4800-6000 mg daily. Four
      years ago, he was referred to our outpatient service, where his Attention Deficit
      Hyperactivity Disorder was re-evaluated. At that point, the patient's daily
      Ritalin(r) dosage was reduced to 200 mg daily orally, but he still experienced
      pronounced symptoms of, Attention Deficit Hyperactivity Disorder so this dosage
      was raised again. The patient's plasma levels consistently remained between 60
      187 nmol/l-within the recommended range-and signs of his obsessive-compulsive
      symptoms diminished with fluoxetine 40 mg daily. Finally, on a dosage of 378 mg
      extended-release methylphenidate (Concerta(r)), his symptoms of Attention Deficit
      Hyperactivity Disorder have improved dramatically and no further use of
      methylphenidate has been recorded during the 24 months preceding this report.
      CONCLUSIONS: Symptoms of Attention Deficit Hyperactivity Disorder (ADHD) in this
      adult patient, who also manifested a co-occurring obsessive compulsive disorder,
      dramatically improved only after application of a higher-than-normal dose of
      methylphenidate. We therefore suggest that clinicians consider these findings in
      relation to their adherence to current therapeutic guidelines.

PMID- 22583959
TI  - Evaluation of a novel non-invasive (13) C-glucose breath test for the
      identification of diabetes mellitus in cirrhotic patients.
AB  - AIM:   Diabetes mellitus (DM) has been reported to worsen the long-term prognosis
      of cirrhotic patients, and many studies have reported that DM is an independent
      risk factor for hepatocellular carcinoma. However, an accurate diagnosis of DM is
      sometimes difficult in cirrhotic patients. Recently, a novel non-invasive (13) C
      glucose breath test has been reported to be useful for diagnosing insulin
      resistance in non-cirrhotic patients. The aim of this study was to evaluate the
      efficacy of this tool for the identification of DM in cirrhotic patients.
      METHODS:   Thirty eight cirrhotic patients with normal fasting serum glucose and
      hemoglobin A1c levels underwent the (13) C-glucose breath test and the oral
      glucose tolerance test. Blood and breath samples were collected at baseline and
      at 30, 60 and 120 min after ingestion of 100 mg (13) C-labeled glucose and 75 g
      glucose. RESULTS:   There was a strong correlation between the change in the
      concentrations at 2 h for the measured (13) C-glucose breath test (2h-BT) and the
      2 h plasma glucose level (r = -0.60, P < 0.0001). In a receiver-operator curve
      analysis using the 2h-BT, the area under the curve was determined to be 0.88,
      with a sensitivity and specificity (cut-off value of 3.50/00) of 82% and 85%,
      respectively, for the detection of DM. Multivariate analysis showed the 2h-BT to
      be an independent parameter to identify DM. CONCLUSION:   The (13) C-glucose
      breath test is a useful tool and has the potential to become a routine outpatient
      examination for the screening of DM in cirrhotic patients.

PMID- 22583958
TI  - HHV-8 reduces dendritic cell migration through down-regulation of cell-surface
      CCR6 and CCR7 and cytoskeleton reorganization.
AB  - BACKGROUND: For an efficient immune response against viral infection, dendritic
      cells (DCs) must express a coordinate repertoire of receptors that allow their
      recruitment to the sites of inflammation and subsequently to the secondary
      lymphoid organs in response to chemokine gradients.Several pathogens are able to
      subvert the chemokine receptor expression and alter the migration properties of
      DCs as strategy to escape from the immune control. FINDINGS: Here we report the
      inhibitory effect of Human Herpesvirus 8 (HHV-8) on the migratory behavior of
      immature and mature DCs. We found that the virus altered the DC chemokine
      receptor expression and chemokine induced migration. Moreover HHV-8 was also able
      to interfere with basal motility of DCs by inducing cytoskeleton modifications.
      CONCLUSION: Based on our findings, we suggest that HHV-8 is able to subvert the
      DC migration capacity and this represents an additional mechanism which
      interferes with their immune-functions.

PMID- 22583960
TI  - Nematomorph parasites indirectly alter the food web and ecosystem function of
      streams through behavioural manipulation of their cricket hosts.
AB  - Nematomorph parasites manipulate crickets to enter streams where the parasites
      reproduce. These manipulated crickets become a substantial food subsidy for
      stream fishes. We used a field experiment to investigate how this subsidy affects
      the stream community and ecosystem function. When crickets were available,
      predatory fish ate fewer benthic invertebrates. The resulting release of the
      benthic invertebrate community from fish predation indirectly decreased the
      biomass of benthic algae and slightly increased leaf break-down rate. This is the
      first experimental demonstration that host manipulation by a parasite can
      reorganise a community and alter ecosystem function. Nematomorphs are common, and
      many other parasites have dramatic effects on host phenotypes, suggesting that
      similar effects of parasites on ecosystems might be widespread.

PMID- 22583961
TI  - Investigations of antimicrobial activity of some Cameroonian medicinal plant
      extracts against bacteria and yeast with gastrointestinal relevance.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Resistance against antibiotics of many bacteria
      is accumulating. Therefore, searches for new substances with antimicrobial
      activity have become an urgent necessity. Medicinal plants are frequently used in
      popular medicine as remedies for many infectious diseases (intestinal infection,
      malaria, tuberculosis, etc.). AIM OF THE STUDY: This study aimed to determine the
      in vitro antimicrobial activity of hexane, ethyl acetate and methanol extracts
      from different parts (leaves, stem bark, entire plant) of five different plant
      species against bacteria and yeast of gastrointestinal relevance. MATERIAL AND
      METHODS: Twenty-one extracts from all the following plants (Albizia gummifera
      (leaf), Ficus exasperata (leaf and stem bark), Nauclea latifolia (leaf and stem
      bark), Ricinodendron heudelotii (stem bark), Senna hirsuta (entire plant) have
      been screened for their antimicrobial activity against eight bacteria species
      including Gram-positive bacteria (Staphylococcus aureus and Bacillus cereus),
      Gram-negative bacteria (Escherichia coli, Shigella dysenteriae, Shigella
      flexneri, Salmonella typhi, Pseudomonas aeruginosa, and Klebsiella pneumoniae)
      and one yeast species (Candida albicans) using agar disc-diffusion, and
      microbroth dilution assays. RESULTS: Results demonstrated that F. exasperata and
      N. latifolia were active against the whole set of tested microorganisms. The
      methanol extract of N. latifolia (leaf and stem bark) was the most active against
      against C. albicans, E. coli, S. aureus, P. aeruginosa with a minimum inhibitory
      concentration (MIC) of 2, 32, 64 and 64 MUg/ml, respectively. The methanol
      extract of leaf of F. exasperata was also most active with significant inhibitory
      activity against E. coli, S. dysenteriae, S. Typhi and P. aeruginosa with MIC
      values of 128 MUg/ml. Only the extract of N. latifolia (stem bark and leaf)
      showed anticandidal property. CONCLUSION: The results show that these plant
      extracts exhibit antimicrobial activity and N. latifolia proved to be most
      effective as an antibacterial and antifungal.

PMID- 22583962
TI  - What ARE Parkinson disease? Non-motor features transform conception of the
      shaking palsy.

PMID- 22583963
TI  - Behavior of resin-based endodontic sealer cements in thin and thick films.
AB  - OBJECTIVES: For root canal fillings, a thin layer of sealer cement is generally
      recommended. However, with resin-based sealers, lower bond strength to dentin has
      been shown in thin layers compared to thick, contrary to typical behavior of
      adhesive layers between two adherents. The aim of this study was to evaluate
      tensile and shear bond strength of thin and thick films of three resin-based
      sealers (one epoxy-based and two methacrylate-based) materials and to investigate
      corner effects of one methacrylate-based resin sealer. METHODS: Freshly mixed
      sealer cements were placed between metal-to-metal surfaces of plano-parallel
      stainless steel aligned rods with diameter 4.7 mm. Ten samples were prepared for
      each type, thickness (0.1 and 1.0 mm) of sealer and test. Tensile and shear
      strengths were measured after 48 h for the methacrylate-based materials and after
      7 days for the epoxy-based material using a universal testing machine at a
      crosshead speed of 1mm/min. Corner effects were investigated using one
      methacrylate-based resin material. RESULTS: Film thickness had a highly
      significant influence on both tensile and shear strengths. For methacrylate resin
      based sealers, thin films had higher bond strength than thick (p<0.001 for both
      tensile and shear bond strength). With the epoxy-based sealer either no
      difference (shear) or lower bond strength in thin films (tensile; p<0.05) was
      found, and appeared to result from numerous voids created during mixing. The
      methacrylate based sealer demonstrated typical engineering behavior for an
      adhesive material, with corner effects shown as a material property and in good
      agreement with the tensile bond strength results. SIGNIFICANCE: The higher
      tensile and shear bond strength of resin-based sealer in thin films is the
      opposite of that previously reported for bonding to dentin. The substrate clearly
      has an important role in failure behavior.

PMID- 22583965
TI  - Association of common variations of 8q24 with the risk of prostate cancer in
      Koreans and a review of the Asian population.
AB  - What's known on the subject? and What does the study add? The association between
      subjects with the genetic variation of 8q24 and the risk of development of
      prostate cancer in Korean men was found. As a result of haplotype analysis, [AGC]
      and [CTA] carriers showed a significant association with prostate cancer risk.
      This is clinically meaningful as an initial study on genetic susceptibility to
      prostate cancer in Korean men and the first report of 8q24 haplotypes in an Asian
      population. OBJECTIVE: To determine the association between genetic variation of
      8q24 with prostate cancer risk in Korean men. PATIENTS AND METHODS: With a
      hospital-based case-control study design, we enrolled 194 patients with prostate
      cancer and 169 healthy controls from visitors for cancer screening. DNA samples
      were obtained from peripheral blood for the analysis of single nucleotide
      polymorphisms (SNPs). Three SNPs of 8q24, including rs16901979, rs6983267, and
      rs1447295, were genotyped on cases and controls. RESULTS: The subjects with the
      rs1447295 CA or AA genotype had a higher risk of prostate cancer than the CC
      genotype. The A allele at SNP rs1447295 was associated with the incidence of
      prostate cancer. The rs16901979 CA genotype carriers had a higher risk of
      prostate cancer than the CC genotype. Individuals with the [AGC] and [CTA]
      haplotypes had a significantly increased risk of prostate cancer compared with
      the [CTC] haplotype ([AGC] with adjusted odds ratio [OR] 1.79; 95% confidence
      interval [CI] 1.09-2.96; P = 0.022; [CTA] with adjusted OR 5.17; 95% CI 2.40
      11.15; P < 0.001). CONCLUSIONS: The genetic variation of 8q24 is associated with
      the risk of prostate cancer in Korean men. Individuals with the [AGC] and [CTA]
      haplotypes had a significant association with prostate cancer risk.

PMID- 22583964
TI  - Association of rs5888 SNP in the scavenger receptor class B type 1 gene and serum
      lipid levels.
AB  - BACKGROUND: Bai Ku Yao is a special subgroup of the Yao minority in China. The
      present study was undertaken to detect the association of rs5888 single
      nucleotide polymorphism (SNP) in the scavenger receptor class B type 1 (SCARB1)
      gene and several environmental factors with serum lipid levels in the Guangxi Bai
      Ku Yao and Han populations. METHODS: A total of 598 subjects of Bai Ku Yao and
      585 subjects of Han Chinese were randomly selected from our stratified randomized
      cluster samples. Genotypes of the SCARB1 rs5888 SNP were determined by polymerase
      chain reaction and restriction fragment length polymorphism combined with gel
      electrophoresis, and then confirmed by direct sequencing. RESULTS: The levels of
      total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density
      lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) AI were lower but ApoB was
      higher in Bai Ku Yao than in Han (P < 0.05-0.001). The frequencies of C and T
      alleles were 78.3% and 21.7% in Bai Ku Yao, and 73.7% and 26.3% in Han (P <
      0.01); respectively. The frequencies of CC, CT and TT genotypes were 60.0%, 36.6%
      and 3.4% in Bai Ku Yao, and 54.2%, 39.0% and 6.8% in Han (P < 0.01);
      respectively. The subjects with TT genotype in both ethnic groups had lower HDL-C
      and ApoAI levels than the subjects with CC or CT genotype (P < 0.05 for all).
      Subgroup analyses showed that the subjects with TT genotype in Bai Ku Yao had
      lower HDL-C and ApoAI levels in males than the subjects with CC or CT genotype (P
      < 0.05 for all), and the T allele carriers had higher TC, LDL-C and ApoB levels
      in females than the T allele noncarriers (P < 0.05 for all). The participants
      with TT genotype in Han also had a lower tendency of HDL-C and ApoAI levels in
      males than the participants with CC or CT genotype, but the difference did not
      reach statistically significant (P = 0.063 and P = 0.086; respectively). The
      association of serum HDL-C and ApoAI levels and genotypes was confirmed by the
      multiple linear regression analysis in both ethnic groups. Serum lipid parameters
      were also correlated with several environmental factors. CONCLUSIONS: The
      differences in serum lipid levels between the two ethnic groups might partially
      attribute to the differences in the SCARB1 rs5888 SNP and several environmental
      factors.

PMID- 22583966
TI  - Surgery: a cost-effective option for drug-resistant epilepsy in China.

PMID- 22583968
TI  - Visible and near-infrared spectra collected from the thumbs of patients with
      chronic fatigue syndrome for diagnosis.
AB  - BACKGROUND: Currently, diagnosis of chronic fatigue syndrome (CFS) is based on
      clinical symptoms and therefore relies on the experience and skill of the
      doctors. Here, we have examined the possible diagnosis of CFS based on spectral
      information and chemometrics analysis, such as principal component analysis (PCA)
      and soft modeling of class analogy (SIMCA). METHODS: Visible and near-infrared
      (Vis-NIR) spectroscopy was used to examine possible changes in the region of 600
      1100 nm in thumbs and assessed. RESULTS: The Vis-NIR spectra of thumbs from 57
      CFS patients and 74 healthy volunteers were subjected to PCA and SIMCA to develop
      multivariate models to discriminate between CFS patients and healthy individuals.
      The model was further assessed by the prediction of 120 determinations (60 in the
      healthy group and 60 in the CFS patient group). The PCA model predicted a
      discrimination of the masked samples; specifically the SIMCA model correctly
      predicted 51 of 60 (83.3%) healthy volunteers and 42 of 60 (70%) CFS patients.
      CONCLUSIONS: Despite the relatively small number of subjects involved in this
      trial, who were exclusively Japanese, our results imply that Vis-NIR spectroscopy
      of the thumb combined with chemometrics analysis may provide a valuable tool for
      diagnosing CFS.

PMID- 22583967
TI  - A sialyltransferase mutant with decreased donor hydrolysis and reduced sialidase
      activities for directly sialylating LewisX.
AB  - Glycosyltransferases are important catalysts for enzymatic and chemoenzymatic
      synthesis of complex carbohydrates and glycoconjugates. The glycosylation
      efficiencies of wild-type glycosyltransferases vary considerably when different
      acceptor substrates are used. Using a multifunctional Pasteurella multocida
      sialyltransferase 1 (PmST1) as an example, we show here that the sugar nucleotide
      donor hydrolysis activity of glycosyltransferases contributes significantly to
      the low yield of glycosylation when a poor acceptor substrate is used. With a
      protein crystal structure-based rational design, we generated a single mutant
      (PmST1 M144D) with decreased donor hydrolysis activity without significantly
      affecting its alpha2-3-sialylation activity when a poor fucose-containing
      acceptor substrate was used. The single mutant also has a drastically decreased
      alpha2-3-sialidase activity. X-ray and NMR structural studies revealed that
      unlike the wild-type PmST1, which changes to a closed conformation once a donor
      binds, the M144D mutant structure adopts an open conformation even in the
      presence of the donor substrate. The PmST1 M144D mutant with decreased donor
      hydrolysis and reduced sialidase activity has been used as a powerful catalyst
      for efficient chemoenzymatic synthesis of complex sialyl Lewis(x) antigens
      containing different sialic acid forms. This work sheds new light on the effect
      of donor hydrolysis activity of glycosyltransferases on glycosyltransferase
      catalyzed reactions and provides a novel strategy to improve glycosyltransferase
      substrate promiscuity by decreasing its donor hydrolysis activity.

PMID- 22583969
TI  - Possible role for glutathione-S-transferase in the oligozoospermia elicited by
      acute zearalenone administration in Swiss albino mice.
AB  - Zearalenone (ZEA) is a non-steroidal estrogenic mycotoxin produced by several
      species of Fusarium, commonly found in the soil in temperate and warm countries
      and is a frequent contaminant of cereal crops worldwide. Accordingly, it has been
      implicated in several mycotoxicosis in farm animals and in humans, but the
      underlying mechanisms remain largely unknown. Therefore, the current study was
      aimed to investigate the effect of an acute dose of ZEA (40 mg/kg, p.o.) on
      reproductive and hematological parameters, as well as on markers of oxidative
      stress in liver, kidney and testes in mice. Adult Swiss albino male mice were
      exposed to a single oral administration of ZEA, and 48 h thereafter behavioral
      and biochemical tests were performed. No differences in locomotor or exploratory
      activity were observed in the open-field test. On the other hand, ZEA increased
      the number of leukocytes, segmented neutrophils, sticks, eosinophils, monocytes
      and decreased platelets and lymphocytes number. Moreover, ZEA drastically reduced
      the number and motility of live spermatozoa. Additionally, while levels of
      thiobarbituric acid reactive substances (TBARS), non-protein thiols (NPSH) and
      ascorbic acid in liver, kidney and testes were not altered by ZEA administration,
      superoxide dismutase activity increased in all tissues evaluated, catalase
      activity increased in the kidney, and glutathione-S-transferase activity
      decreased in kidney and testes. In summary, we showed that ZEA have acute toxic
      effects mainly in reproductive system of adult male Swiss albino mice and its
      effect probably is related to a reduced activity of GST and increased in SOD
      activity in testes.

PMID- 22583970
TI  - The simultaneous expression of both ephrin B3 receptor and E-cadherin in
      Barrett's adenocarcinoma is associated with favorable clinical staging.
AB  - BACKGROUND: In intestinal epithelium, tyrosine kinase receptor Ephrin B3 (Eph B3)
      maintains the architecture of the crypt-villus axis by repulsive interaction with
      its ligand ephrin-B1. While loss of Eph B3 is linked to colorectal cancer
      initiation, overexpression of Eph B3 in cancer cell lines inhibits growth and
      induces functional changes with decreased mesenchymal and increased epithelial
      markers. In order to study this tumor suppressor activity of Eph B3 in esophageal
      adenocarcinoma we analyzed the simultaneous expression of Eph B3 and E-cadherin
      in both the healthy esophagus and in Barrett's carcinoma. METHODS: Simultaneous
      expression of Eph B3 and E-cadherin was investigated in samples from 141 patients
      with Barrett's carcinoma and from 20 healthy esophagi using immunhistology and
      quantitative PCR. Results from healthy squamous epithelium, Barrett's metaplasia
      and staging-specific esophageal adenocarcinoma were correlated. RESULTS: A
      significantly reduced E-cadherin mRNA expression could be detected in
      adenocarcinoma compared to dysplasia. The immunhistological activity of E
      cadherin and Eph B3 was reduced in adenocarcinoma compared to dysplasia or
      healthy esophageal mucosa. The intracellular E-cadherin distribution changed
      significantly from the cytoplasm to the membrane, when the Eph receptor was
      simultaneously expressed. Simultaneous expression of E-cadherin and Eph B3 showed
      a significant inverse correlation to tumor stage. CONCLUSIONS: We present novel
      evidence of the tumor suppressor activity of Eph B3 in esophageal adenocarcinoma
      possibly due to the impact on redistribution of cellular E-cadherin to the
      membrane. Our results suggest that this effect might play a role in the dysplasia
      adenocarcinoma sequence, the infiltrative growth pattern and the development of
      lymph node metastases.

PMID- 22583975
TI  - Detection and characterization of hepatitis E virus in domestic pigs of different
      ages in Portugal.
AB  - This study represents the primary hepatitis E virus (HEV) surveillance in
      domestic pigs in Portugal, five pig farms were investigated in 5 different
      Portuguese regions, ten faecal samples were collected at four different stages of
      the production. All faecal samples were tested for hepatitis E virus by real-time
      RT-PCR. At least one sample from each farms of all age groups tested positive for
      HEV. The prevalence in the pig herds varied from 10% to 30% and the mean
      prevalence was 32% in weaners, 20% in growers, 32% in fatteners and 4% in adult
      dry sows. Phylogenetic analysis of the detected HEV sequences indicated that the
      circulating virus strains belong under the genotype 3.

PMID- 22583977
TI  - Benign multicystic peritoneal mesothelioma mimicking recurrence of an ovarian
      borderline tumor: a case report.
AB  - INTRODUCTION: Benign multicystic peritoneal mesothelioma is an extremely rare
      tumor that occurs mainly in women in their reproductive age. Its preoperative
      diagnosis and adequate treatment are quite difficult to attain. CASE
      PRESENTATION: Our patient was a 23-year-old Japanese woman who had a history of
      right oophorectomy and left ovarian cystectomy for an ovarian tumor at 20 years
      of age. The left ovarian tumor had been diagnosed on histology as a mucinous
      borderline tumor. Two years and nine months after the initial operation, multiple
      cysts were found in our patient. A laparotomy was performed and her uterus, left
      ovary, omentum and pelvic lymph nodes were removed due to suspicion of recurrence
      of the borderline tumor. A histological examination, however, revealed that the
      cysts were not a recurrence of the borderline tumor but rather benign multicystic
      peritoneal mesothelioma. There were no residual lesions and our patient was
      followed up with ultrasonography. She remains free from recurrence nine months
      after treatment. CONCLUSION: We report a case of benign multicystic peritoneal
      mesothelioma mimicking recurrence of an ovarian borderline tumor. Benign
      multicystic peritoneal mesothelioma should be suspected when a multicystic lesion
      is present in the pelvis as in the case presented here, especially in patients
      with previous abdominal surgery.

PMID- 22583976
TI  - miRFANs: an integrated database for Arabidopsis thaliana microRNA function
      annotations.
AB  - BACKGROUND: Plant microRNAs (miRNAs) have been revealed to play important roles
      in developmental control, hormone secretion, cell differentiation and
      proliferation, and response to environmental stresses. However, our knowledge
      about the regulatory mechanisms and functions of miRNAs remains very limited. The
      main difficulties lie in two aspects. On one hand, the number of experimentally
      validated miRNA targets is very limited and the predicted targets often include
      many false positives, which constrains us to reveal the functions of miRNAs. On
      the other hand, the regulation of miRNAs is known to be spatio-temporally
      specific, which increases the difficulty for us to understand the regulatory
      mechanisms of miRNAs. DESCRIPTION: In this paper we present miRFANs, an online
      database for Arabidopsis thalianamiRNA function annotations. We integrated
      various type of datasets, including miRNA-target interactions, transcription
      factor (TF) and their targets, expression profiles, genomic annotations and
      pathways, into a comprehensive database, and developed various statistical and
      mining tools, together with a user-friendly web interface. For each miRNA target
      predicted by psRNATarget, TargetAlign and UEA target-finder, or recorded in
      TarBase and miRTarBase, the effect of its up-regulated or down-regulated miRNA on
      the expression level of the target gene is evaluated by carrying out differential
      expression analysis of both miRNA and targets expression profiles acquired under
      the same (or similar) experimental condition and in the same tissue. Moreover,
      each miRNA target is associated with gene ontology and pathway terms, together
      with the target site information and regulating miRNAs predicted by different
      computational methods. These associated terms may provide valuable insight for
      the functions of each miRNA. CONCLUSION: First, a comprehensive collection of
      miRNA targets for Arabidopsis thaliana provides valuable information about the
      functions of plant miRNAs. Second, a highly informative miRNA-mediated genetic
      regulatory network is extracted from our integrative database. Third, a set of
      statistical and mining tools is equipped for analyzing and mining the database.
      And fourth, a user-friendly web interface is developed to facilitate the browsing
      and analysis of the collected data.

PMID- 22583978
TI  - Pediatric combined heart-liver transplantation performed en bloc: a single-center
      experience.
AB  - Pediatric CHLT is rarely performed in transplant centers and even fewer are
      performed en bloc. In the hands of an experienced surgeon with the appropriate
      patient selection, CHLT performed en bloc may have several operative and
      immunologic benefits, thereby resulting in improved outcomes for the transplant
      recipient. A single-institutional, retrospective review from 1/1/06 to 12/31/10
      was conducted. Three pediatric patients with end-stage heart and liver disease
      who were considered low immunologic risk were included. All were managed by the
      same surgeon with a herein-described CHLT donor and recipient operation. Data
      were collected on patient and graft survival, rejection episodes, infectious
      complications, operative time, intraoperative transfusion requirements, and
      immunosuppression regimens. One-yr patient and graft survival rates were 100%. No
      patients experienced antibody-mediated or cell-mediated rejection. No patients
      had postoperative infections, and all patients were free of opportunistic
      infections at one-yr post-transplant. All patients were maintained safely on
      steroid-free immunosuppression. There were no intraoperative complications. In
      pediatric end-stage heart and liver disease patients with low immunologic risk,
      it is reasonable to proceed with en bloc CHLT so long as there is an experienced
      surgeon to perform the case. This offers operative and immunologic advantages to
      the recipient while maintaining equivalent, if not improved, recipient and graft
      outcomes.

PMID- 22583979
TI  - Evaluation of the ArcCHECK QA system for IMRT and VMAT verification.
AB  - The purposes of this study were to perform tests for the ArcCHECK QA system, and
      to evaluate the suitability of this system for IMRT and VMAT verification. The
      device was tested for short term reproducibility, dose linearity, dose rate
      dependence, dose per pulse dependence, field size dependence, out of field
      dependence and directional dependence. Eight simple plans that each used four
      beams of different field sizes as well as IMRT and VMAT plans for various organs
      of 10 patients were measured by ArcCHECK. The phantom data was then compared with
      ion chamber measurements and planned results. The ArcCHECK diodes performed well
      for all tests except directional dependence, which varies from a minimum of -4.9%
      (seen only when the beam is incident on the diode at 180 degrees ) to a maximum
      of 9.1% (approximately at 105 degrees ). For simple plan verification, the
      absolute dose pass rates of gamma index (3%/3 mm) were almost identical. They had
      an average pass rate of 94.6% +/- 1.3% when the field size was <=20 cm in the X
      direction (right to left direction), but the pass rate fell rapidly when the
      field size was >20 cm in the X direction. For all patient-specific IMRT and VMAT
      QA, the pass rates exceeded 95% and 93%, respectively, and high reproducibility
      of these results has been observed from week to week. The comparative
      measurements show that the ArcCHECK QA system is completely suitable for clinical
      IMRT and VMAT verification.

PMID- 22583980
TI  - The impact of early life exposure to diagnostic and therapeutic radiation on
      childhood cancer risk.

PMID- 22583981
TI  - Multi-parametric fit method in reconstruction of brachytherapy needles.
AB  - PURPOSE: To adapt the multi-parametric fit method to reconstruct brachytherapy
      needles inserted with free hand technique for treatment of surface malignancies.
      METHODS: An alternative reconstruction method for brachytherapy (BT) needles is
      presented. The method is based on the digitized tip and end coordinates on pairs
      of posterior-anterior and posterior-oblique reconstruction images obtained with a
      non-isocentric C-arm. The needles tip and end coordinates are computed with the
      multi-parametric fit method that also incorporates the determination of the
      magnification factors of the reconstruction images. We tested the reconstruction
      accuracy with radio-opaque markers inserted into known positions. The range of C
      arm angles that resulted in an accurate reconstruction was also investigated. We
      applied the method in treatments of the vulvar cancer using 3 to 5 pieces of BT
      needles located in a distance of approximately 1 cm. RESULTS: The phantom test
      showed largest difference between the reconstructed and expected distance between
      the simulated needles +/-1.3 mm. In vulvar insertions, the reconstructed position
      of the BT needles obtained with different image pairs agreed within 3 mm.
      CONCLUSION: The reconstruction accuracy of the multi-parametric fit method in
      with proper imaging is suitable for the clinical use.

PMID- 22583982
TI  - Anhedonic-like traits and lack of affective deficits in 18-month-old C57BL/6
      mice: Implications for modeling elderly depression.
AB  - The prevalence of depression increases with aging. We hypothesized that like
      humans, old animals exhibit anhedonic-like behavior, along with signs of
      behavioral despair. In rodents, anhedonia, a reduced sensitivity to reward, which
      is listed as a core feature of major depression in the DSM-IVR, can be measured
      by a decrease in intake of and preference for sweet solutions. Here, sucrose
      intake, forced swimming, immobility in the modified tail suspension test, novelty
      exploration, grooming, anxiety and locomotor activity were compared in naive 3-
      and 18-month-old male C57BL/6 mice. The absolute amounts and the ratio of
      consumed 1% sucrose solution to water intake was significantly smaller in 18
      month-old mice than in 3-month-old mice. The consumption of 5%-sucrose solution
      requiring high levels of drinking effort, novelty exploration in two setups and
      grooming behavior in the splash test were reduced in older animals. Analysis of
      other behaviors suggested that the above-mentioned signs of anhedonic-like traits
      were unlikely to be attributable to the potential effect of aging on metabolic
      needs for water, taste perception, motor capabilities or the induction of
      essential anxiety and neophobia. A 4-week treatment with the antidepressant
      imipramine (7mg/kg/day) or dimebon, a compound with suggested neuroprotective
      proneurogenic properties (1mg/kg/day) restored sucrose intake and preference in
      18-month-old mice. Meanwhile, young and old mice showed no differences in the
      parameters of behavioral despair evaluated in the forced swim and modified tail
      suspension tests. Thus, the behavioral profile of aged mice parallels that of
      humans with elderly depression, in whom the symptoms of hedonic deficits
      typically outweigh affective disturbances. The assessment of anhedonic-like
      traits with the sucrose preference test in 18-month-old mice will be useful in
      preclinical studies of elderly depression.

PMID- 22583983
TI  - The consumption of a Jerte Valley cherry product in humans enhances mood, and
      increases 5-hydroxyindoleacetic acid but reduces cortisol levels in urine.
AB  - PURPOSE: Jerte Valley cherries contain high levels of tryptophan, serotonin, and
      melatonin. These molecules have been shown to be involved in mood regulation. It
      has been suggested that a complex inter-relationship between brain serotonin,
      circulating levels of cortisol (the major stress hormone), and the hypothalamus
      pituitary-adrenal axis exists in the regulation of stress responses, where
      cortisol and serotonin act as markers of mood disturbances. Moreover there is
      growing evidence that altered HPA activity is associated with various age-related
      pathologies. The present study evaluated the effect of the ingestion of a Jerte
      Valley cherry-based product, compared to a placebo product, on urine cortisol and
      5-hydroxyindoleacetic acid (5-HIAA) levels, and on mood in young, middle-aged,
      and elderly participants. METHODS: Cortisol and 5-HIAA acid levels were measured
      by commercial enzyme-linked immunosorbent assay kits. The mood state profile was
      analysed using a visual analogue scale and the state-trait anxiety inventory.
      RESULTS: Our findings showed that the ingestion of the Jerte Valley cherry
      product decreased urinary cortisol and increased urinary 5-HIAA levels in all the
      experimental groups. Moreover, the cherry product was able to lessen anxiety
      status in the middle-aged and elderly participants, and enhanced subjective mood
      parameters, particularly family relationships in young participants, and frame of
      mind and fitness in both middle-aged and elderly subjects. CONCLUSIONS: The
      consumption of the Jerte Valley cherry product may protect against stress and act
      as a mood enhancer by increasing serotonin availability to the organism,
      particularly with advancing age.

PMID- 22583985
TI  - The evolution of salinity tolerance in Daphnia: a functional genomics approach.
AB  - One route to genetic adaptation in a novel environment is the evolution of
      ecological generalisation. Yet, identifying the cost that a generalist pays for
      the increased breadth of tolerance has proven elusive. We integrate phenotypic
      assays with functional genomics to understand how tolerance to a salinity
      gradient evolves, and we test the relationship between the fitness cost of this
      generalisation and the cost of transcription that arises from evolved differences
      in patterns of gene expression. Our results suggest that a salt-tolerant genotype
      of Daphnia is characterised by constitutively expressed genes, which does not
      incur a loss of fitness or a cost of transcription relative to a salt-intolerant
      genotype in low saline environments. We find that many genes whose expression
      pattern evolved in response to salinity are also involved in the response to
      predators, suggesting that the cost of generalisation may be due to trade-offs
      along other environmental axes.

PMID- 22583984
TI  - Reasons for not using ecstasy: a qualitative study of non-users, ex-light users
      and ex-moderate users.
AB  - BACKGROUND: Although ecstasy is often consumed in the electronic music scene, not
      everyone with the opportunity to use it chooses to do so. The objective of this
      study was to understand the reasons for non-use or the cessation of use, which
      could provide information for public health interventions. METHODS: A qualitative
      reference method was used. Our "snowball" sample group consisted of 53 people who
      were split into three subgroups: non-users (NU, n = 23), ex-light users (EX-L, n
      = 12) and ex-moderate users (EX-M, n = 18). Individual, semi-structured
      interviews were conducted, transcribed and subjected to content analysis with the
      aid of NVivo8. RESULTS: Adverse health effects and personal values were given as
      reasons for non-use in the three groups. Non-users (NU) and ex-light users (EX-L)
      provided reasons that included fear of possible effects as well as moral, family
      and religious objections. Ex-moderate users (EX-M) cited reasons related to
      health complications and concomitant withdrawal from the electronic music scene.
      However, most of the ex-moderate users did not rule out the possibility of future
      use. CONCLUSIONS: Potential effects and undesirable consequences appear to guide
      the decisions within the different groups. Prevention might target these
      motivations. Individuals who have used ecstasy indicate that social and
      environmental factors are the most important factors.

PMID- 22583986
TI  - Currently available quality improvement initiatives in surgical oncology.
AB  - For most cancers, surgical therapy offers the only hope for cure. Nevertheless,
      evidence suggests wide variation in cancer care, and therefore it is imperative
      to ensure that high standards of care are being met. Few initiatives currently
      exist that are focused on cancer care quality, and there is no program measuring
      short-term surgical outcomes following cancer surgery. Improvements in care will
      likely come from performance programs that provide reliable, robust, and
      actionable information in a timely manner such that performance feedback can
      occur more frequently and at earlier stages in the treatment and disease process.

PMID- 22583987
TI  - Monitoring the delivery of cancer care: Commission on Cancer and National Cancer
      Data Base.
AB  - The primary objective of the Commission on Cancer (CoC) is to ensure the delivery
      of comprehensive, high-quality care that improves survival while maintaining
      quality of life for patients with cancer. This article examines the initiatives
      of the CoC toward achieving this goal, utilizing data from the National Cancer
      Data Base (NCDB) to monitor treatment patterns and outcomes, to develop quality
      measures, and to benchmark hospital performance. The article also highlights how
      these initiatives align with the Institute of Medicine's recommendations for
      improving the quality of cancer care and briefly explores future projects of the
      CoC and NCDB.

PMID- 22583988
TI  - Variation in mortality after high-risk cancer surgery: failure to rescue.
AB  - Surgical mortality with oncologic surgery varies widely in the United States.
      Patients, providers, and payers are paying closer attention to these variations
      and a way of reducing them. Although different hospital and surgical technologies
      and processes of care may account for some of this variation, there is an
      increasing awareness of the role of hospital safety culture. There is a growing
      body of evidence suggesting the importance of reducing mortality rates after
      major complications as a means to reducing the disparate mortality rates with
      oncologic surgery.

PMID- 22583989
TI  - Unexpected readmissions after major cancer surgery: an evaluation of readmissions
      as a quality-of-care indicator.
AB  - Readmissions following major oncologic operation are common-affecting patient
      treatment, outcome, and hospital resources. The Center for Medicare and Medicaid
      Services mandates reporting of certain disease-specific readmissions and Congress
      is considering using individual hospital readmission rates as a performance
      measure. Studies using administrative data demonstrate that readmission rates
      following major cancer surgery are high. Administrative data cannot determine
      causes. Single-institution studies demonstrate length of hospital stay and
      comorbidities as risk factors. Discharge processes and outpatient healthcare
      utilization can be improved. Until studies on readmission rate are conducted,
      using readmission rates as a measure of quality should be pursued cautiously.

PMID- 22583990
TI  - Importance of and adherence to lymph node staging standards in gastrointestinal
      cancer.
AB  - In gastrointestinal oncology, one of the most important factors influencing
      cancer-specific survival is the presence of positive lymph nodes. Although it
      remains controversial, adequate lymph node examination is required for accurate
      staging such that patients can receive appropriate adjuvant treatments and for
      stratification in clinical trials. Nevertheless, wide variation exists in the
      quality of lymph node examination in the United States, and many centers are not
      meeting guideline treatment recommendations.

PMID- 22583992
TI  - Prediction tools in surgical oncology.
AB  - Artificial neural networks, prediction tables, and clinical nomograms allow
      physicians to transmit an immense amount of prognostic information in a format
      that exhibits comprehensibility and brevity. Current models demonstrate the
      feasibility to accurately predict many oncologic outcomes, including pathologic
      stage, recurrence-free survival, and response to adjuvant therapy. Although
      emphasis should be placed on the independent validation of existing prediction
      tools, there is a paucity of models in the literature that focus on quality of
      life outcomes. The unification of tools that predict oncologic and quality of
      life outcomes into a comparative effectiveness table will furnish patients with
      cancer with the information they need to make a highly informed and
      individualized treatment decision.

PMID- 22583991
TI  - Racial differences and disparities in cancer care and outcomes: where's the rub?
AB  - Despite a profusion of studies over the past several years documenting racial
      differences in cancer outcomes, there is a paucity of data as to the root causes
      underlying these observations. This article reviews work to date focusing on
      black-white differences in cancer outcomes, explores potential mechanisms
      underlying these differences, and identifies patient, physician, and health care
      system factors that may account for persistent racial disparities in cancer care.
      Research strategies to elucidate the relative influence of these various factors
      and policy recommendations to reduce persistent disparities are also discussed.

PMID- 22583993
TI  - Randomized controlled trials in surgical oncology: where do we stand?
AB  - This article reviews the history of clinical trials in surgery using breast
      cancer surgery and rectal cancer surgery as examples. Trials in breast cancer
      have transformed the surgical management of this disease. Rectal cancer surgery
      has also changed greatly, but much of this evolution occurred outside the setting
      of clinical trials. This article highlights the strengths and limitations of
      surgical trials and suggests that future studies should include pretrial
      credentialing as a requirement for surgeon participation. More work needs to be
      done to bridge the gap from trial results to implementation of new techniques in
      clinical practice.

PMID- 22583994
TI  - Patient safety in surgical oncology: perspective from the operating room.
AB  - Despite knowledge that most surgical adverse events occur in the operating room
      (OR), understanding of the intraoperative phase of care is incomplete; most
      studies measure surgical safety in terms of preoperative risk or postoperative
      morbidity and mortality. Because of the OR's complexity, human factors
      engineering provides an ideal methodology for studies of intraoperative safety.
      This article reviews models of error and resilience as delineated by human
      factors experts, correlating them to OR performance. Existing methodologies for
      studying intraoperative safety are then outlined, focusing on video-based
      observational research. Finally, specific human and system factors examined in
      the OR are detailed.

PMID- 22583995
TI  - Appropriate use of surgical procedures for patients with cancer.
AB  - With increasing focus on improving quality and promoting patient-centered care,
      ensuring that patients receive appropriate surgical procedures is paramount. The
      appropriateness method was developed to determine which patients should and
      should not undergo surgical intervention versus medical therapy. This method
      combines the best available evidence in the literature with expert opinion to
      produce explicit guidance for clinicians on the relative risks and benefits of a
      procedure for specific clinical indications. A coordinated effort to produce
      appropriateness criteria for surgical oncology could improve the quality of
      surgical care for patients with cancer if these criteria are integrated into
      routine clinical practice.

PMID- 22583996
TI  - Collaboration with the community cancer center: benefit for all.
AB  - Developing successful programs in a community cancer center involves
      collaborative efforts between employed and private practice physicians, hospital
      and cancer center administrations, support personnel, and significant resources,
      coupled with a vision that will lead to improved patient care and outcomes.
      Collaboration through a strong state cancer control program is another important
      component for a successful community cancer center. Delaware has one of the best
      state cancer control programs in the United States. In 2001, the Delaware Cancer
      Consortium was formed, which, in 2002, launched its first statewide program to
      screen all Delawareans older than 50 years with colonoscopy.

PMID- 22583997
TI  - Value-based health care: a surgical oncologist's perspective.
AB  - There is ongoing debate on how to reform the health care system. Value-based
      systems have been proposed to account for both quality and cost. The primary goal
      of value-based health care is to achieve good health outcomes for patients with
      consideration of dollars spent. To do so, it is imperative that health care
      providers define meaningful outcome metrics for specific medical conditions and
      consider the full cycle of care as well as multiple dimensions of care.

PMID- 22583998
TI  - Outcomes research in surgical oncology. Foreword.

PMID- 22583999
TI  - Outcomes research in surgical oncology.

PMID- 22584000
TI  - Is reentry critical for visual awareness of object presence?
AB  - Reentrant processing has been proposed as a critical mechanism in visual
      perception of an object's features. In order to test whether reentry is critical
      for visual awareness of object presence, the success of reentry was manipulated
      with object substitution masking (OSM) while participants performed a forced
      choice target present-absent task and rated their subjective confidence in each
      trial. Signal detection analyses were performed on the data from the forced
      choice task and on the subjective confidence ratings. The results showed that OSM
      reduced sensitivity to the presence of the target, indicating that reentry is
      critical for awareness of object presence. Consistent with the idea that OSM
      leaves feedforward processing intact, confidence ratings in reported target
      absent trials were lower for misses (target present, no response) than for
      correct rejections (target absent, no response), implying that a target-related
      sensory signal was available for subjective ratings in spite of reported absence
      of the target. The results suggest that reentry is critical for encoding the
      target representation into a stable, consciously reportable form.

PMID- 22584001
TI  - Primary myelolipoma presenting as a nasal cavity polyp: a case report and review
      of the literature.
AB  - INTRODUCTION: Myelolipomas are rare, benign tumors comprising mature adipose
      tissue and hematopoietic elements. The vast majority occur within the adrenal
      glands, but extra-adrenal myelolipomas have also been reported in the presacral
      region, retroperitoneum, mesentery, stomach, spleen, liver, mediastinum and
      lungs. Here, we present a case of primary myelolipoma occurring in an unusual
      site: the nasal cavity. To the best of our knowledge, we believe that this
      location for extra-adrenal myelolipoma has not been previously described in the
      literature. CASE PRESENTATION: We report a case of primary myelolipoma occurring
      in the nasal cavity of a 48-year-old Asian woman. We describe the etiology,
      pathology and differential diagnosis of extra-adrenal myelolipomas, and review
      the literature. CONCLUSIONS: We chose to present this case because of its unusual
      location. Although myelolipomas are rare, we conclude that they it should be
      considered in the differential diagnosis of lesions in this site.

PMID- 22584002
TI  - Oleamide activates peroxisome proliferator-activated receptor gamma (PPARgamma)
      in vitro.
AB  - BACKGROUND: Oleamide (ODA) is a fatty acid primary amide first identified in the
      cerebrospinal fluid of sleep-deprived cats, which exerts effects on vascular and
      neuronal tissues, with a variety of molecular targets including cannabinoid
      receptors and gap junctions. It has recently been reported to exert a
      hypolipidemic effect in hamsters. Here, we have investigated the nuclear receptor
      family of peroxisome proliferator-activated receptors (PPARs) as potential
      targets for ODA action. RESULTS: Activation of PPARalpha, PPARbeta and PPARgamma
      was assessed using recombinant expression in Chinese hamster ovary cells with a
      luciferase reporter gene assay. Direct binding of ODA to the ligand binding
      domain of each of the three PPARs was monitored in a cell-free fluorescent ligand
      competition assay. A well-established assay of PPARgamma activity, the
      differentiation of 3T3-L1 murine fibroblasts into adipocytes, was assessed using
      an Oil Red O uptake-based assay. ODA, at 10 and 50 MUM, was able to transactivate
      PPARalpha, PPARbeta and PPARgamma receptors. ODA bound to the ligand binding
      domain of all three PPARs, although complete displacement of fluorescent ligand
      was only evident for PPARgamma, at which an IC50 value of 38 MUM was estimated.
      In 3T3-L1 cells, ODA, at 10 and 20 MUM, induced adipogenesis. CONCLUSIONS: We
      have, therefore, identified a novel site of action of ODA through PPAR nuclear
      receptors and shown how ODA should be considered as a weak PPARgamma ligand in
      vitro.

PMID- 22584003
TI  - Plasma high sensitivity C-reactive protein and its relationship with cytokine
      levels in children with newly diagnosed type 1 diabetes and ketoacidosis.
AB  - BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) and pro-inflammatory
      cytokines have been suggested as sensitive markers of endothelial dysfunction.
      Our aim was to monitor plasma hs-CRP levels at different time-points and in
      different degrees of ketoacidosis severity, its association with cytokine levels
      and its role as a marker of severe ketoacidosis complications. PATIENTS AND
      METHODS: We studied in 38 newly diagnosed children with type 1 diabetes and
      ketoacidosis, aged 7.7 +/- 3.1 years, hs-CRP, white blood cell count (WBC), and
      plasma levels of cytokines IL-1beta (interleukin-1beta), IL-2, IL-6, IL-8, IL-10,
      TNF-alpha (tumor necrosis factor-alpha) prior to and during DKA management.
      RESULTS: On admission, the levels of WBC, PMN, IL-6 and IL-10 were elevated, but
      were all reduced within 120 h after ketoacidosis management. In the group with
      moderate/severe ketoacidosis, but not in mild ketoacidosis, hs-CRP levels were
      significantly reduced at 24h (p=0.021), WBC and IL-6 at 120 h (p=0.003), while IL
      10 was prematurely reduced at 6-8h (p=0.008). Moreover hs-CRP was significantly
      associated with WBC (p=0.023) and IL-6 (p=0.028) on admission, with IL-6
      (p=0.002) and IL-8 (p=0.014) at 24h and with IL-10 (p=0.027) at 120 h. The above
      were not observed in the group with mild ketoacidosis. CONCLUSIONS: In the
      children with moderate/severe diabetic ketoacidosis of our study, increased
      levels of hs-CRP and IL-6 were observed, together with leukocytosis and
      neutrophilia, without the presence of infection. As hs-CRP was found to be
      strongly associated with the inflammatory IL-6, the prolonged elevation of hs-CRP
      levels in children with severe ketoacidosis could serve as a marker for the
      development of its severe complications.

PMID- 22584004
TI  - Molecular typing of Mycoplasma agalactiae: tracing European-wide genetic
      diversity and an endemic clonal population.
AB  - Mycoplasma agalactiae causes chronic infections in small ruminants and remains
      endemic in many regions of the world, despite intensive and costly eradication
      programs. In this study, the innate genomic plasticity of M. agalactiae was
      exploited to design and assess a combination of molecular epidemiological tools
      to trace the pathogen in different geographic locations and to understand its
      emergence or re-emergence after eradication campaigns. For this purpose, two
      collections of M. agalactiae isolates, representing European outbreaks or
      localized endemic disease in a single region of France, were subjected to RFLP
      (Restriction Fragment Length Polymorphism) analyses using two sets of DNA probes
      (distributed across the genome and specific for the vpma gene locus), and a
      previously described VNTR (Variable Number Tandem Repeats) analysis. A
      combination of four genome-specific DNA probes and two VNTRs gave the highest
      discriminative power. Molecular typing revealed that, while isolates from diverse
      geographical origins fell into clearly different groups, the endemic disease
      repeatedly observed in the Western Pyrenees region over the past 30 years has
      been caused by a unique subtype of M. agalactiae. This indicates that the re
      emergence of the pathogen after seemingly successful eradication programs is not
      due to the importation of exotic strains, but to the persistence of local
      reservoirs of infection.

PMID- 22584005
TI  - Computational identification of microRNAs in Anatid herpesvirus 1 genome.
AB  - BACKGROUND: MicroRNAs (miRNAs) are a group of short (~22 nt) noncoding RNAs that
      specifically regulate gene expression at the post-transcriptional level. miRNA
      precursors (pre-miRNAs), which are imperfect stem loop structures of ~70 nt, are
      processed into mature miRNAs by cellular RNases III. To date, thousands of miRNAs
      have been identified in different organisms. Several viruses have been reported
      to encode miRNAs. FINDINGS: Here, we extended the analysis of miRNA-encoding
      potential to the Anatid herpesvirus 1 (AHV-1). Using computational approaches, we
      found that AHV-1 putatively encodes 12 mature miRNAs. We then compared the 12
      mature miRNAs candidates with the all known miRNAs of the herpesvirus family.
      Interestingly, the "seed sequences" (nt 2 to 8) of 2 miRNAs were predicted to
      have the high conservation in position and/or sequence with the 2 miRNAs of
      Marek's disease virus type 1 (MDV-1). Additionally, we searched the targets from
      viral mRNAs. CONCLUSIONS: Using computational approaches, we found that AHV-1
      putatively encodes 12 mature miRNAs and 2 miRNAs have the high conservation with
      the 2 miRNAs of MDV-1. The result suggested that AHV-1 and MDV-1 should have
      closed evolutionary relation, which provides a valuable evidence of
      classification of AHV-1. Additionally, seven viral gene targets were found, which
      suggested that AHV-1 miRNAs could affect its own gene expression.

PMID- 22584006
TI  - Understanding Li diffusion in Li-intercalation compounds.
AB  - Intercalation compounds, used as electrodes in Li-ion batteries, are a
      fascinating class of materials that exhibit a wide variety of electronic,
      crystallographic, thermodynamic, and kinetic properties. With open structures
      that allow for the easy insertion and removal of Li ions, the properties of these
      materials strongly depend on the interplay of the host chemistry and crystal
      structure, the Li concentration, and electrode particle morphology. The large
      variations in Li concentration within electrodes during each charge and discharge
      cycle of a Li battery are often accompanied by phase transformations. These
      transformations include order-disorder transitions, two-phase reactions that
      require the passage of an interface through the electrode particles, and
      structural phase transitions, in which the host undergoes a crystallographic
      change. Although the chemistry of an electrode material determines the voltage
      range in which it is electrochemically active, the crystal structure of the
      compound often plays a crucial role in determining the shape of the voltage
      profile as a function of Li concentration. While the relationship between the
      voltage profile and crystal structure of transition metal oxide and sulfide
      intercalation compounds is well characterized, far less is known about the
      kinetic behavior of these materials. For example, because these processes are
      especially difficult to isolate experimentally, solid-state Li diffusion, phase
      transformation mechanisms, and interface reactions remain poorly understood. In
      this respect, first-principles statistical mechanical approaches can elucidate
      the effect of chemistry and crystal structure on kinetic properties. In this
      Account, we review the key factors that govern Li diffusion in intercalation
      compounds and illustrate how the complexity of Li diffusion mechanisms correlates
      with the crystal structure of the compound. A variety of important diffusion
      mechanisms and associated migration barriers are sensitive to the overall Li
      concentration, resulting in diffusion coefficients that can vary by several
      orders of magnitude with changes in the lithium content. Vacancy clusters,
      groupings of vacancies within the crystal lattice, provide a common mechanism
      that mediates Li diffusion in important intercalation compounds. This mechanism
      emerges from specific crystallographic features of the host and results in a
      strong decrease of the Li diffusion coefficient as Li is added to an already Li
      rich host. Other crystallographic and electronic factors, such as the proximity
      of transition metal ions to activated states of hops and the occurrence of
      electronically induced distortions, can result in a strong dependence of the Li
      mobility on the overall Li concentration. The insights obtained from fundamental
      studies of ionic diffusion in electrode materials will be instrumental for
      physical chemists, chemical engineers, synthetic chemists, and materials and
      device designers who are developing these technologies. 

PMID- 22584008
TI  - Variation in osteocytes morphology vs bone type in turtle shell and their
      exceptional preservation from the Jurassic to the present.
AB  - Here we describe variations in osteocytes derived from each of the three bone
      layers that comprise the turtle shell. We examine osteocytes in bone from four
      extant turtle species to form a morphological 'baseline', and then compare these
      with morphologies of osteocytes preserved in Cenozoic and Mesozoic fossils. Two
      different morphotypes of osteocytes are recognized: flattened-oblate osteocytes
      (FO osteocytes), which are particularly abundant in the internal cortex and
      lamellae of secondary osteons in cancellous bone, and stellate osteocytes (SO
      osteocytes), principally present in the interstitial lamellae between secondary
      osteons and external cortex. We show that the morphology of osteocytes in each of
      the three bone layers is conserved through ontogeny. We also demonstrate that
      these morphological variations are phylogenetically independent, as well as
      independent of the bone origin (intramembranous or endochondral). Preservation of
      microstructures consistent with osteocytes in the morphology in Cenozoic and
      Mesozoic fossil turtle bones appears to be common, and occurs in diverse
      diagenetic environments including marine, freshwater, and terrestrial deposits.
      These data have potential to illuminate aspects of turtle biology and evolution
      previously unapproachable, such as estimates of genome size of extinct species,
      differences in metabolic rates among different bones from a single individual,
      and potential function of osteocytes as capsules for preservation of ancient
      biomolecules.

PMID- 22584007
TI  - Black bear parathyroid hormone has greater anabolic effects on trabecular bone in
      dystrophin-deficient mice than in wild type mice.
AB  - Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disease that has
      deleterious consequences in muscle and bone, leading to decreased mobility,
      progressive osteoporosis, and premature death. Patients with DMD experience a
      higher-than-average fracture rate, particularly in the proximal and distal femur
      and proximal tibia. The dystrophin-deficient mdx mouse is a model of DMD that
      demonstrates muscle degeneration and fibrosis and osteoporosis. Parathyroid
      hormone, an effective anabolic agent for post-menopausal and glucocorticoid
      induced osteoporosis, has not been explored for DMD. Black bear parathyroid
      hormone (bbPTH) has been implicated in the maintenance of bone properties during
      extended periods of disuse (hibernation). We cloned bbPTH and found 9 amino acid
      residue differences from human PTH. Apoptosis was mitigated and cAMP was
      activated by bbPTH in osteoblast cultures. We administered 28nmol/kg of bbPTH 1
      84 to 4-week old male mdx and wild type mice via daily (5*/week) subcutaneous
      injection for 6 weeks. Vehicle-treated mdx mice had 44% lower trabecular bone
      volume fraction than wild type mice. No changes were found in femoral cortical
      bone geometry or mechanical properties with bbPTH treatment in wild type mice,
      and only medio-lateral moment of inertia changed with bbPTH treatment in mdx
      femurs. However, MUCT analyses of the trabecular regions of the distal femur and
      proximal tibia showed marked increases in bone volume fraction with bbPTH
      treatment, with a greater anabolic response (7-fold increase) in mdx mice than
      wild type mice (2-fold increase). Trabecular number increased in mdx long bone,
      but not wild type bone. Additionally, greater osteoblast area and decreased
      osteoclast area were observed with bbPTH treatment in mdx mice. The heightened
      response to PTH in mdx bone compared to wild type suggests a link between
      dystrophin deficiency, altered calcium signaling, and bone. These findings
      support further investigation of PTH as an anabolic treatment for DMD-induced
      osteoporosis.

PMID- 22584010
TI  - Percutaneous cryoablation of solitary sporadic renal cell carcinomas.
AB  - What's known on the subject? and What does the study add? Percutaneous renal
      cryoablation is a safe and effective treatment for patients with small renal
      masses, who are poor surgical candidates. Oncological outcomes from previous
      percutaneous ablation studies are difficult to interpret because of the large
      number of patients treated with a history of RCC (38% in our experience) and the
      large number of treated renal masses without a pathology-proven diagnosis. This
      cryoablation study addresses these issues by evaluating only solitary, sporadic
      biopsy-proven RCC. Oncological outcomes and complications were also evaluated by
      tumour T-stage, which allows some degree of comparison with previously published
      surgical results. OBJECTIVE: * To evaluate retrospectively our single institution
      experience with percutaneous cryoablation of solitary, sporadic renal cell
      carcinomas (RCCs), and to compare the efficacy and safety of this technique for
      treatment of different T-stage RCC. PATIENTS AND METHODS: * 116 patients were
      treated with percutaneous cryoablation for a solitary, sporadic biopsy-proven RCC
      in a single treatment session between November 2003 and November 2010. * The
      technical success of the ablation procedure, complications and evidence for local
      or metastatic tumour recurrence were evaluated for each patient. RESULTS: * 83
      patients (72%) were treated for a stage T1a RCC, 27 patients (23%) for a stage
      T1b RCC, and six patients (5%) for a stage T2 RCC. * Technical success was
      achieved in the treatment of 115 of 116 (99%) renal tumours. The single technical
      failure occurred in the treatment of a 4.3-cm RCC. * Local recurrent tumour was
      identified in one of 88 patients (1%) with follow-up computed tomography (CT) or
      magnetic resonance imaging available for review >3 months from the time of
      ablation. The median (range) imaging follow-up in these patients was 21 (3-73)
      months. The local tumour recurrence was identified on CT 11 months after the
      ablation procedure in a patient treated for a 2.7 cm RCC. * None of the patients
      developed metastatic RCC. * The major complication rate was 4% for patients with
      stage T1a tumours, 15% for those with stage T1b tumours, and 33% for those with
      stage T2 tumours. There were no procedural-related deaths. CONCLUSIONS: *
      Percutaneous renal cryoablation of RCC can be performed with high technical
      success in patients with tumours up to, and beyond 7 cm in maximum diameter. *
      The tumour recurrence rate after percutaneous renal cryoablation was low, and
      recurrence was not related to tumour size in this group of patients. *
      Statistically significant higher complication rates were seen with treatment of
      larger (higher T-stage) RCCs.

PMID- 22584009
TI  - Low magnitude mechanical signals mitigate osteopenia without compromising
      longevity in an aged murine model of spontaneous granulosa cell ovarian cancer.
AB  - Cancer progression is often paralleled by a decline in bone mass, raising risk of
      fracture. Concerns persist regarding anabolic interventions for skeletal
      protection, as these may inadvertently exacerbate neoplastic tissue expansion.
      Given bone's inherent mechanosensitivity, low intensity vibration (LIV), a
      mechanical signal that encourages osteoblastogenesis, could possibly slow cancer
      associated bone loss, but this goal must be achieved without fostering disease
      progression. Seventy 12w female F1-SWRxSWXJ-9 mice, a strain prone to developing
      granulosa cell tumors, were randomized into baseline control (BC: n=10), age
      matched control (AC: n=30), and LIV (n=30), which received mechanical signals
      (90Hz @ 0.3g) for 15m/day, 5 day/w over the course of 1 year. Survival curves for
      AC (10 died) and LIV (8 died) followed similar trends (p=0.62), indicating
      longevity was unperturbed by LIV. At 1 year, bone volume of proximal tibiae in
      LIV mice was 25% greater than AC (p<0.02), while bone volume of L5 vertebrae was
      16% higher in LIV over AC (p<0.02). Primary lesions and peripheral metastases
      were apparent in both LIV and AC; however, overall tumor incidence was
      approximately 30% less in LIV (p=0.27) and, when disease was evident, involved
      fewer organ systems (p=0.09). Marrow-derived mesenchymal stem cells (MSC) were
      52% lower (p<0.01) in LIV, and 31% lower (p=0.08) in mice lacking pathology,
      suggesting higher MSC levels in this model of cancer susceptibility may have
      contributed to tumor progression. These experiments indicate that LIV helps
      protect bone mass in mice inherently susceptible to cancer without compromising
      life expectancy, perhaps through mechanical control of stem cell fate. Further,
      these data reflect the numerous system-level benefits of exercise in general, and
      mechanical signals in particular, in the preservation of bone density and the
      suppression of cancer progression.

PMID- 22584011
TI  - The use of the Internet in collecting CDI data--an example from Norway.
AB  - This article presents the methodology used in a population-based study of early
      communicative development in Norwegian children using an adaptation of the
      MacArthur-Bates communicative development inventories (CDI), comprising
      approximately 6500 children aged between 0.8 and 3.0. To our knowledge, this is
      the first CDI study collecting data via the Internet. After a short description
      of the procedures used in adapting the CDI to Norwegian and the selection of
      participants, we discuss the advantages and potential pitfalls of using web-based
      forms as a method of data collection. We found that use of web-based forms was
      far less time-consuming, and therefore also far less expensive than the
      traditional paper-based forms. The risk of coding errors was virtually eliminated
      with this method. We conclude that in a society with high access to the Internet,
      this is a method well worth pursuing.

PMID- 22584012
TI  - Role of polyphenols in cell death control.
AB  - Dietary consumption of fruit, vegetables, fish, and olive oil has been
      demonstrated to exert beneficial effects on human health. This finding may be due
      to the high content of antioxidant compounds including polyphenols. Current
      evidence strongly supports a contribution of polyphenols  to the prevention of
      several chronic degenerative diseases such as cancer, atherosclerosis and
      cardiovascular diseases, central nervous system disorders, as well as aging.
      Apoptosis is a genetically controlled and evolutionarily conserved form of cell
      death of critical importance for the maintenance  of tissue homeostasis in the
      adult organism. The malfunction of the death machinery may play a primary role in
      various pathologic processes, leading to proliferative or degenerative diseases.
      Polyphenols can interact with specific steps and/or proteins regulating the
      apoptotic process in different  ways depending on their concentration, the cell
      system, the type or stage of the pathological process. Because of their ability
      to modulate cell death, polyphenols have been proposed as chemopreventive and
      therapeutic agents. This paper reviews and discusses the last 3-year findings
      related  to the principal molecular mechanisms involved in the control of the
      balance between apoptosis and cell proliferation exerted by polyphenols.

PMID- 22584014
TI  - Early outcome in renal transplantation from large donors to small and size
      matched recipients - a porcine experimental model.
AB  - Kidney transplantation from a large donor to a small recipient, as in pediatric
      transplantation, is associated with an increased risk of thrombosis and DGF. We
      established a porcine model for renal transplantation from an adult donor to a
      small or size-matched recipient with a high risk of DGF and studied GFR, RPP
      using MRI, and markers of kidney injury within 10 h after transplantation. After
      induction of BD, kidneys were removed from ~63-kg donors and kept in cold storage
      for ~22 h until transplanted into small (~15 kg, n = 8) or size-matched (n = 8)
      recipients. A reduction in GFR was observed in small recipients within 60 min
      after reperfusion. Interestingly, this was associated with a significant
      reduction in medullary RPP, while there was no significant change in the size
      matched recipients. No difference was observed in urinary NGAL excretion between
      the groups. A significant higher level of HO-1 mRNA was observed in small
      recipients than in donors and size-matched recipients indicating cortical injury.
      Improvement in early graft perfusion may be a goal to improve short- and long
      term GFR and avoid graft thrombosis in pediatric recipients.

PMID- 22584015
TI  - Integration of cellular signals in chattering environments.
AB  - Cells are constantly exposed to fluctuating environmental conditions. External
      signals are sensed, processed and integrated by cellular signal transduction
      networks, which translate input signals into specific cellular responses by means
      of biochemical reactions. These networks have a complex nature, and we are still
      far from having a complete characterization of the process through which they
      integrate information, specially given the noisy environment in which that
      information is embedded. Guided by the many instances of constructive influences
      of noise that have been reported in the physical sciences in the last decades,
      here we explore how multiple signals are integrated in an eukaryotic cell in the
      presence of background noise, or chatter. To that end, we use a Boolean model of
      a typical human signal transduction network. Despite its complexity, we find that
      the network is able to display simple patterns of signal integration.
      Furthermore, our computational analysis shows that these integration patterns
      depend on the levels of fluctuating background activity carried by other cell
      inputs. Taken together, our results indicate that signal integration is sensitive
      to environmental fluctuations, and that this background noise effectively
      determines the information integration capabilities of the cell.

PMID- 22584013
TI  - Development of high amylose wheat through TILLING.
AB  - BACKGROUND: Wheat (Triticum spp.) is an important source of food worldwide and
      the focus of considerable efforts to identify new combinations of genetic
      diversity for crop improvement. In particular, wheat starch composition is a
      major target for changes that could benefit human health. Starches with increased
      levels of amylose are of interest because of the correlation between higher
      amylose content and elevated levels of resistant starch, which has been shown to
      have beneficial effects on health for combating obesity and diabetes. TILLING
      (Targeting Induced Local Lesions in Genomes) is a means to identify novel genetic
      variation without the need for direct selection of phenotypes. RESULTS: Using
      TILLING to identify novel genetic variation in each of the A and B genomes in
      tetraploid durum wheat and the A, B and D genomes in hexaploid bread wheat, we
      have identified mutations in the form of single nucleotide polymorphisms (SNPs)
      in starch branching enzyme IIa genes (SBEIIa). Combining these new alleles of
      SBEIIa through breeding resulted in the development of high amylose durum and
      bread wheat varieties containing 47-55% amylose and having elevated resistant
      starch levels compared to wild-type wheat. High amylose lines also had reduced
      expression of SBEIIa RNA, changes in starch granule morphology and altered starch
      granule protein profiles as evaluated by mass spectrometry. CONCLUSIONS: We
      report the use of TILLING to develop new traits in crops with complex genomes
      without the use of transgenic modifications. Combined mutations in SBEIIa in
      durum and bread wheat varieties resulted in lines with significantly increased
      amylose and resistant starch contents.

PMID- 22584016
TI  - Theoretical study of the flow rate toward the right heart territory in case of
      total occlusion of the right coronary artery.
AB  - In this work, patients with severe coronary disease and chronic occlusion of the
      right coronary artery (RCA) are studied. In this clinical situation, the
      collateral circulation is an important factor in the preservation of the
      myocardium until reperfusion of the area at risk. An accurate estimation of
      collateral flow is crucial in surgical bypass planning as it can influence the
      outcome of a given treatment for a given patient. The evaluation of collateral
      flow is frequently achieved using an index (CFI, Collateral Flow Index) based on
      pressure measurements. Using a model of the coronary circulation based on
      hydraulic/electric analogy, we demonstrate, through theoretical simulations, that
      a wide range of fractional collateral flow values can be obtained for any given
      distal pressure difference depending on the values of the capillary and
      collateral resistances.

PMID- 22584018
TI  - Comparison of human lung tissue mass measurements from ex vivo lungs and high
      resolution CT software analysis.
AB  - BACKGROUND: Quantification of lung tissue via analysis of computed tomography
      (CT) scans is increasingly common for monitoring disease progression and for
      planning of therapeutic interventions. The current study evaluates the
      quantification of human lung tissue mass by software analysis of a CT to physical
      tissue mass measurements. METHODS: Twenty-two ex vivo lungs were scanned by CT
      and analyzed by commercially available software. The lungs were then dissected
      into lobes and sublobar segments and weighed. Because sublobar boundaries are not
      visually apparent, a novel technique of defining sublobar segments in ex vivo
      tissue was developed. The tissue masses were then compared to measurements by the
      software analysis. RESULTS: Both emphysematous (n = 14) and non-emphysematous (n
      = 8) bilateral lungs were evaluated. Masses (Mean +/- SD) as measured by
      dissection were 651 +/- 171 g for en bloc lungs, 126 +/- 60 g for lobar segments,
      and 46 +/- 23 g for sublobar segments. Masses as measured by software analysis
      were 598 +/- 159 g for en bloc lungs, 120 +/- 58 g for lobar segments, and 45 +/-
      23 g for sublobar segments. Correlations between measurement methods was above
      0.9 for each segmentation level. The Bland-Altman analysis found limits of
      agreement at the lung, lobe and sublobar levels to be -13.11% to -4.22%, -13.59%
      to 4.24%, and -45.85% to 44.56%. CONCLUSION: The degree of concordance between
      the software mass quantification to physical mass measurements provides
      substantial evidence that the software method represents an appropriate non
      invasive means to determine lung tissue mass.

PMID- 22584017
TI  - Low-dose oral prednisone improves clinical and ultrasonographic remission rates
      in early rheumatoid arthritis: results of a 12-month open-label randomised study.
AB  - INTRODUCTION: In early rheumatoid arthritis (RA), low-dose oral prednisone (PDN)
      co-medication yields better clinical results than monotherapy with disease
      modifying anti-rheumatic drugs (DMARDs). In addition, ultrasonography (US)
      evaluation reveals rapid and significant effects of glucocorticosteroids on
      subclinical synovitis. No data currently exist that examine the clinical and US
      results offered by glucocorticoid co-medication over DMARD monotherapy in early
      RA patients. METHODS: Two hundred and twenty patients with early RA (< 1 year
      from clinical onset) were treated according to a low disease activity (LDA)
      targeted step-up protocol including methotrexate (MTX) and, in the active
      treatment arm, low-dose (6.25 mg/day) oral PDN over 12 months. Clinical disease
      activity measures were collected at baseline, 2, 4, 6, 9 and 12 months, and US
      examination of hands was performed at baseline, 6 and 12 months. Grey-scale and
      power Doppler (PD) synovitis were scored (0 to 3) for each joint. At 12 months,
      clinical remission according to the disease activity score among 28 joints was
      defined as the clinical outcome, and a total joint PD score of 0 (PD negativity)
      as the imaging outcome. RESULTS: Each group included 110 patients with comparable
      demographic, clinical, laboratory and US characteristics. At 12 months, the LDA
      rate was similar in the two groups, whilst the clinical remission rate (risk
      ratio = 1.61 (95% confidence interval = 1.08, 2.04)) and PD negativity rate (risk
      ratio = 1.31 (95% confidence interval = 1.04, 1.64)) were significantly higher in
      the MTX+PDN group. CONCLUSION: In early RA, despite a similar response rate in
      terms of LDA, low-dose oral PDN co-medication led to a higher proportion of
      clinical remission and PD negativity compared with MTX monotherapy, thus ensuring
      a better disease activity control. TRIAL REGISTRATION NUMBER: Current Controlled
      Trials ISRCTN2486111.

PMID- 22584019
TI  - Predictive value of confocal scanning laser for the onset of visual field loss in
      glaucoma suspects.
AB  - PURPOSE: To perform a longitudinal multivariate analysis of the ability of
      Moorfields Regression Analysis (MRA) to predict the onset of glaucoma in a
      population of patients with suspected glaucoma due to appearance of the optic
      nerve head. DESIGN: Prospective longitudinal evaluation of a diagnostic test.
      PARTICIPANTS: Single, randomly selected eye of prospectively recruited patients
      with suspected glaucoma based on the optic nerve head appearance on
      stereophotographs and normal baseline visual field results. METHODS: The MRA was
      evaluated at baseline (Heidelberg Retina Tomograph; Heidelberg Engineering,
      Dossenheim, Germany), and visual field tests were repeated every 6 months. A
      longitudinal multivariate proportional hazard ratio (HR) analysis was performed,
      and likelihood ratios and positive and negative predictive values were compared.
      MAIN OUTCOME MEASURES: Onset of visual field losses. RESULTS: The study included
      230 eyes that were followed up during a mean period of 62+/-14 months, ranging
      from 4 to 7 years. The predicted HR (for onset of visual field losses) of the MRA
      temporal-inferior sector outside normal limits was 3.65 (95% confidence interval
      [CI], 2.32-5.75; P < 0.0001). An MRA temporal-superior sector outside normal
      limits had an HR of 3.43 (95% CI, 2.21-5.32; P < 0.0001). CONCLUSIONS: The
      temporal-inferior and temporal-superior positions of the MRA are highly
      predictive for the onset of visual field loss in glaucoma suspects.

PMID- 22584020
TI  - Ocular adverse events of systemic inhibitors of the epidermal growth factor
      receptor: report of 5 cases.
AB  - PURPOSE: To describe the ocular effects associated with the administration of the
      systemic epidermal growth factor receptor (EGFR) inhibitors panitumumab and
      erlotinib. DESIGN: Retrospective, noncomparative interventional case series.
      PARTICIPANTS: Ten eyes of 5 patients in treatment with systemic EGFR inhibitors,
      4 patients with erlotinib for end-stage lung carcinoma, and 1 patient with
      panitumumab for end-stage colorectal cancer. METHODS: Data collected from charts
      included gender, age at presentation, systemic disease, and clinical presentation
      in each eye. MAIN OUTCOME MEASURES: Demographics on presentation and clinical
      findings. RESULTS: Multiple epithelial defects were observed in all 10 eyes,
      corneal melting and thinning were observed in 3 eyes of 2 patients, 2 eyes of 1
      patient presented with lower lid ectropion, and 2 eyes of 2 patients presented
      with corneal perforation, both requiring a penetrating keratoplasty. CONCLUSIONS:
      Severe ocular side effects, including corneal perforation, may be associated with
      the use of the EGFR inhibitors panitumumab and erlotinib.

PMID- 22584021
TI  - Association between genetic variants associated with vertical cup-to-disc ratio
      and phenotypic features of primary open-angle glaucoma.
AB  - PURPOSE: To assess the association between the genetic variants associated with
      the optic nerve vertical cup-to-disc ratio (VCDR) and the phenotypic features in
      patients with primary open-angle glaucoma (POAG), including normal-tension
      glaucoma (NTG) and high-tension glaucoma (HTG). DESIGN: Case-control study.
      PARTICIPANTS AND CONTROLS: Japanese patients with NTG (n = 213) and HTG (n = 212)
      and 191 control subjects without glaucoma. METHODS: DNA samples were genotyped
      for 7 single nucleotide polymorphisms (SNPs) associated with VCDR: rs1063192
      (near gene: CDKN2B), rs10483727 (SIX1), rs17146964 (SCYL1), rs1547014 (CHEK2),
      rs1900004 (ATOH7), rs1926320 (DCLK1), and rs12015126 (RERE). MAIN OUTCOME
      MEASURES: The VCDR was compared between genotypes, and allele frequency
      differences were compared between NTG or HTG subjects and control subjects.
      Demographic and clinical features were compared between alleles in patients with
      NTG or HTG. RESULTS: There were significant VCDR differences (P = 0.0077 and P =
      0.019) between the genotypes for rs1063192 (CDKN2B) and rs1547014 (CHEK2),
      respectively. There were significant differences in the rs1063192 (CDKN2B) and
      rs1900004 (ATOH7) allele frequencies between the NTG subjects and control
      subjects (P = 0.0023 and P = 0.028, respectively) and a significant difference (P
      = 0.013) in the rs1547014 (CHEK2) allele frequencies between the HTG subjects and
      control subjects. Ages at diagnosis were significantly different in the NTG
      subjects with and without the rs10483727 (SIX1) C allele (P = 0.017) or the
      rs1926320 (DCLK1) T allele (P = 0.040). Likewise, the age at diagnosis was
      significantly different (P = 0.037) in the HTG subjects with and without the
      rs12025126 (RERE) T allele. There were no significant associations between the
      maximum intraocular pressure (IOP) and 7 genotyped SNP alleles in patients with
      NTG or HTG. CONCLUSIONS: The rs1063192 (CDKN2B) and rs1900004 (ATOH7) seem to be
      non-IOP-related genetic risk factors for NTG, and the rs1547014 (CHEK2) is a
      genetic risk factor for HTG. Although the rs10483727 (SIX1), rs1926320 (DCLK1),
      or rs12025126 (RERE) alone may not be sufficient for the development of POAG, the
      association of these SNPs with a phenotypic feature in patients with NTG or HTG
      suggests that these loci contribute to the pathogenesis of POAG.

PMID- 22584022
TI  - Integration of immunodeficiency virus in oocytes via intracytoplasmic injection:
      possible but extremely unlikely.
AB  - OBJECTIVE: To determine if human oocytes can be infected with HIV-1 via
      intracytoplasmic injection and to determine the infection threshold. DESIGN:
      Twenty-eight donated immature and unfertilized human oocytes from HIV-negative
      women were injected with 4 * 10(4) HIV-1 virions and 13 oocytes were used as
      uninjected controls. To determine the infection threshold, 543 cat oocytes were
      injected with 4 * 10(4), 4 * 10(2), or 40 copies of feline immunodeficiency virus
      (FIV) and 376 oocytes were used as controls. SETTING: Academic hospital.
      PATIENT(S)/ANIMAL(S): Donated immature human oocytes and mature cat oocytes.
      INTERVENTION(S): Injection with HIV-1 or FIV. MAIN OUTCOME MEASURE(S): Viral
      integration as measured by fluorescent in situ hybridization with HIV-1-specific
      probes or by nested FIV polymerase chain reaction. RESULT(S): We detected viral
      integration in three of 28 (11%) human oocytes injected with 4 * 10(4) copies of
      HIV-1. When injected with high dose FIV (4 * 10(4) copies) 16%-49% of cat oocytes
      showed viral integration. This decreased to 2%-7% and 0.6%-1.8% when an
      intermediate (4 * 10(2) copies) or low (40 copies) dose was injected,
      respectively. CONCLUSION(S): Human and cat oocytes can be infected with HIV-1 and
      FIV respectively, when injected with high amounts of virus. The probability of
      viral integration is extremely low when small amounts of virus particles are
      injected. Taking into account the small volume injected during intracytoplasmic
      injection, the chances of viral integration are 0.00002%.

PMID- 22584023
TI  - The effect of body mass index on the outcomes of first assisted reproductive
      technology cycles.
AB  - OBJECTIVE: To provide assisted reproductive technology (ART) outcome rates per
      body mass index (BMI) category after controlling for potential confounders.
      DESIGN: Retrospective cohort study. SETTING: Large university-affiliated
      infertility practice. PATIENT(S): Women undergoing ART. INTERVENTION(S): None.
      MAIN OUTCOME MEASURE(S): The primary outcome was live birth. Analyses were
      stratified according to BMI category and adjusted for potential confounders,
      including maternal and paternal age, baseline serum FSH, duration of gonadotropin
      stimulation, mean daily gonadotropin dose, peak serum E(2), number of oocytes
      retrieved, use of intracytoplasmic sperm injection, embryo quality and number,
      transfer day, and number of embryos transferred. RESULT(S): We analyzed the first
      autologous fresh IVF or IVF-ICSI cycle of 4,609 patients. There were no
      differences in the rates of cycle cancellation, spontaneous abortion, biochemical
      and ectopic pregnancies, or multiple births. After adjusting for potential
      confounders, patients with BMI >= 30.0 kg/m(2) had significantly decreased odds
      of implantation, clinical pregnancy, and live birth. The adjusted odds ratio (95%
      confidence interval [CI]) of live birth were 0.63 (0.47-0.85) for BMI 30.00
      34.99, 0.39 (0.25-0.61) for BMI 35.00-39.99, and 0.32 (0.16-0.64) for BMI >= 40.0
      compared with normal-weight cohorts. CONCLUSION(S): Obesity has a significant
      negative effect on ART outcomes. Patients with BMI > 30 kg/m(2) have up to 68%
      lower odds of having a live birth following their first ART cycle compared with
      women with BMI < 30.

PMID- 22584024
TI  - Management of a cervical heterotopic pregnancy presenting with first-trimester
      bleeding: case report and review of the literature.
AB  - OBJECTIVE: To report a rare case of a cervical heterotopic pregnancy resulting
      from intrauterine insemination (IUI) that presented with first-trimester
      bleeding. DESIGN: Case report and literature review. SETTING: Large university
      affiliated infertility practice. PATIENT(S): A 40-year-old gravida 2 para 1 Asian
      woman at 7-3/7 weeks gestational age following clomiphene citrate/IUI for the
      treatment of secondary infertility presented with heavy vaginal bleeding for
      several days. INTERVENTION(S): Transvaginal ultrasound on admission revealed a
      single live intrauterine pregnancy and a cervical gestational sac containing a
      nonviable embryo. The patient continued to have vaginal bleeding and 2 days later
      underwent removal of the cervical ectopic pregnancy tissue with ring forceps, as
      well as an ultrasound-guided intracervical Foley balloon and cerclage placement.
      The bleeding subsided, and 48 hours later the Foley and cerclage were removed.
      MAIN OUTCOME MEASURE(S): Pregnancy outcome. RESULT(S): The remainder of the
      pregnancy was uncomplicated and the patient had a full-term cesarean delivery for
      footling breech of a healthy male infant. CONCLUSION(S): Cervical heterotopic
      pregnancy is a very rare event that almost universally results from infertility
      treatment. We present a case where we were able to remove the cervical ectopic
      and tamponade the bleeding, thus preserving the intrauterine pregnancy for this
      subfertile couple, and we review the existing literature.

PMID- 22584025
TI  - Strain-specific spontaneous activation during mouse oocyte maturation.
AB  - OBJECTIVE: To examine whether spontaneous oocyte activation is determined by
      genetic differences and interacts with culture environment. DESIGN: Experimental
      study. SETTING: Temple University School of Medicine. ANIMAL(S): C57BL/6, DBA/2,
      C3H/HeJ, and A/J strains, along with reciprocal F1 hybrid female mice (5-6
      weeks). INTERVENTION(S): Immature oocytes from different mouse strains collected
      and cultured in different maturation conditions, including different serum, serum
      replacement, bovine serum albumin (BSA), and follicle-stimulation hormone (FSH).
      MAIN OUTCOME MEASURE(S): The emission of first polar body, pronucleus formation,
      meiotic arrest, spontaneous activation, and expression of maturation regulators.
      RESULT(S): Oocytes from C57BL/6 mice display a high rate of delayed first meiotic
      division and spontaneous activation after the first meiotic division with in
      vitro maturation (IVM), and the second meiotic division with in vivo maturation
      (VVM) after superovulation. Spontaneous activation with IVM is sensitive to
      culture environment. Oocytes that spontaneously activated during the first
      meiotic division with IVM have unusual replicated sister chromatid pairs with
      slight connections at centromeres at first mitosis, whereas oocytes that
      activated in vivo display haploidization from the second meiotic division.
      Spontaneous activation is also seen in F1 hybrid oocytes, indicating a dominant
      trait from C57BL/6. Delayed meiosis was associated with reduced cyclin B and
      securin expression. CONCLUSION(S): Both mouse strain and culture environment have
      a statistically significant effect on the incidence of meiotic defects and
      spontaneous activation. Reduced expression of meiotic regulators may underlie
      this effect.

PMID- 22584026
TI  - Sirt1 exerts anti-inflammatory effects and promotes steroidogenesis in Leydig
      cells.
AB  - OBJECTIVE: To investigate the anti-inflammatory effects of Sirt1 and its roles in
      steroidogenesis in Leydig cells. DESIGN: In vitro cell culture study. SETTING:
      Reproductive medical center. ANIMAL(S): C57BL/6 male mice. INTERVENTION(S): TM3
      Leydig cells were treated with proinflammatory cytokines including tumor necrosis
      factor-alpha, interleukin-6, or interleukin-1beta. MAIN OUTCOMES MEASURE(S):
      Sirt1 mRNA and protein levels were measured by real-time polymerase chain
      reaction and Western blotting in TM3 Leydig cells treated with proinflammatory
      cytokines. The cell viability was determined using MTT and BrdU incorporation
      assays. The effect of Sirt1 on the coactivation of steroidogenic factor 1 (SF-1)
      was characterized by coimmunoprecipitation and luciferase reporter assays.
      RESULT(S): Sirt1 mRNA and protein levels were significantly down-regulated by
      proinflammatory cytokines treatment in TM3 Leydig cells. Sirt1 agonist or
      overexpression could efficiently protect cytotoxicity induced by proinflammatory
      cytokines. Sirt1 promoted steroidogenesis through its coactivation of SF-1.
      CONCLUSION(S): Sirt1 plays protective roles and promotes steroidogenesis in
      Leydig cells through its anti-inflammatory actions and coactivation of SF-1.

PMID- 22584027
TI  - Human colon cell culture models of different transformation stages to assess
      conjugated linoleic acid and conjugated linolenic acid metabolism: Challenges and
      chances.
AB  - Both cellular transformation status and cell culture conditions affect fatty acid
      metabolism. Hence, the incorporation and metabolism of c9,t11-CLA (conjugated
      linoleic acid) and other CFAs (conjugated fatty acids) were compared in colon
      cells (LT-97, adenoma; HT-29, adenocarcinoma). Growth inhibition by CFA in LT-97
      cells was assessed via the DAPI (4',6-diamidino-2-phenylindole dihydrochloride)
      assay. Basal gene expression of desaturases (Delta5, Delta6 and Delta9) and
      elongases (1, 2, 5 and 6) was determined in LT-97 using PCR. Analysis of cellular
      fatty acids revealed a 2-fold higher incorporation of c9,t11-CLA (40 and 80MUM)
      in HT-29 cells compared to LT-97 cells. The beta-oxidized and elongated
      conjugated dienoic (CD) fatty acids differed by 8-fold (CD-C16:2/CD-C20:2; HT-29:
      8:1; LT-97: 1:1). Notably, LT-97 cells were shown to convert conjugated linolenic
      acid (CLnA) to CLA. Moreover, LT-97 cells revealed no basal expression of
      elongase 2. CLnA caused stronger growth inhibition (<=80MUM) compared to CLA
      (200MUM). The results indicate that LT-97 cells represent a superior model to
      carry out elongation and desaturation studies of unsaturated and conjugated fatty
      acids compared to HT-29 cells. Nevertheless, further in-depth metabolic and
      transcriptomic analyses are required to confirm this suggestion.

PMID- 22584028
TI  - Demystifying ethnic/sex differences in kidney function: is the difference in
      (estimating) glomerular filtration rate or in serum creatinine concentration?
AB  - BACKGROUND: The recent evaluation of the Chronic Kidney Disease Epidemiology
      Collaboration (CKD-EPI) equation for estimating the glomerular filtration rate
      (GFR) in multiple ethnicities has raised the question on how well this equation
      performs for African-American and Asian subjects. There is no doubt that serum
      creatinine (Scr) concentration differs between ethnicities and sexes. We show
      that creatinine-based equations for white populations may be inaccurate for
      estimating GFR in other ethnic/gender groups, especially in populations from
      Asia. METHODS: This study presents a mathematical analysis of the CKD-EPI
      equation complemented with a literature review of median and reference values for
      IDMS-standardized Scr-concentrations for multiple ethnicities. RESULTS: The study
      shows that at equal eGFR-CKD-EPI-values, the ratio of Scr between females and
      males equals 0.79 and between other ethnicities/sexes and white males is constant
      too. From this information, it is possible to calculate mean Scr-values that
      correspond very well with literature values directly obtained from Scr
      distributions in healthy white males and females and in black males, but the
      discrepancy is larger for other populations. CONCLUSIONS: Our results confirm the
      criticism that has been raised for using the CKD-EPI-equation for these
      ethnicities. An alternative eGFR-model is proposed based on a population
      normalized Scr that needs further validation.

PMID- 22584029
TI  - Association of an Osteopontin gene promoter polymorphism with susceptibility to
      diabetic nephropathy in Asian Indians.
AB  - Genetic predisposition has been proposed to be a major determinant in the
      development of renal complications of diabetes. Osteopontin (OPN) has been
      suggested to be associated with renal diseases characterized by
      tubulointerstitial fibrosis and proteinuria. However, information on association
      of genetic polymorphisms in OPN with diabetic nephropathy is lacking. Thus, the
      present study was designed with the aim to examine the association of an OPN gene
      promoter polymorphism with diabetic nephropathy in Asian Indians. OPN C-443T
      (rs11730582) polymorphism was determined in 1115 type 2 diabetic patients
      belonging to two independently ascertained cohorts using Real time PCR based
      Taqman assay. We observed a nearly threefold elevated risk of diabetic
      nephropathy among carriers of T allele and TT genotype of OPN C-443T
      polymorphism. Further, this allele was found to be significantly associated with
      proteinuria and lower eGFR, a hallmark of diabetic nephropathy, in both our
      cohorts. This is the first study which suggests that OPN C-443T polymorphism may
      be a significant risk factor for diabetic nephropathy in type 2 diabetic
      patients.

PMID- 22584030
TI  - Effects of adrenal dysfunction and high-dose adrenocorticotropic hormone on NMDA
      induced spasm seizures in young Wistar rats.
AB  - Infantile spasms (IS) is a devastating epilepsy syndrome treated with
      adrenocorticotropic hormone (ACTH). To demonstrate the effects of adrenal
      dysfunction, adrenalectomy (ADX) and N-methyl-d-aspartate (NMDA)-induced rat
      model studies of IS were performed. The latency of the seizure in the ADX group
      decreased and the severity of seizures increased significantly. Hippocampal
      corticotropin-releasing hormone (CRH) mRNA was overexpressed in ADX rats. After
      ACTH administration, the latency increased and the severity of seizures decreased
      significantly. ADX increased seizure susceptibility of the rats to NMDA.
      Pretreatment with a single high dose of ACTH caused an obvious reduction in
      susceptibility to NMDA-induced seizures and suppressed CRH mRNA expression. These
      findings are especially useful for IS patients with adrenal diseases and worthy
      of further clinical study.

PMID- 22584031
TI  - Low testosterone levels are related to poor prognosis factors in men with
      prostate cancer prior to treatment.
AB  - What's known on the subject? and What does the study add? Prostate growth is
      ruled by testosterone. Nevertheless, the paradigm that high testosterone levels
      induce prostate cancer development or lead to a poor prognosis in prostate cancer
      is not supported by evidence. A growing number of studies suggest that, on the
      contrary, low testosterone levels are related to poor prognosis features in
      prostate cancer such as higher prostate-specific antigen or higher Gleason score.
      Our experience shows that testosterone levels are related to risk of progression
      of prostate cancer - those men with lower testosterone levels are at higher risk
      of progression of their prostate cancer after treatment delivery. OBJECTIVES: *
      Low testosterone levels have been related to a higher diagnosis of prostate
      cancer (PCa). Hormonal levels have been related to poor prognosis factors in men
      with PCa, mainly after radical prostatectomy. * Our aim was to determine the
      relationship between hormonal levels and PCa prognosis factors in men with PCa
      prior to the onset of treatment. PATIENTS AND METHODS: * We prospectively
      analysed 137 males diagnosed in our centre with PCa with 5+5 core prostate
      biopsies from February 2007 to December 2009. * As part of our clinical protocol,
      we performed hormonal determination (testosterone and sex hormone binding
      globulin) following International Society of Andrology, International Society for
      the Study of the Aging Male and European Association of Urology recommendations.
      * Free testosterone and bioavailable testosterone were calculated using
      Vermeulen's formula. * Age, prostate-specific antigen (PSA), free to total PSA,
      PSA density, number of previous biopsies, digital rectal examination staging,
      Gleason score, percentage of tumour in the biopsy sample, bilaterality of the
      tumour and risk of progression group were prospectively recorded. RESULTS: *
      Higher testosterone levels were related to lower digital rectal examination
      staging (P= 0.02) and lower PSA level (P= 0.05). Higher testosterone was not
      related to lower Gleason score (P= 0.08). * Testosterone was inversely related to
      PCa bilaterality (P < 0.01) and percentage of tumour in the biopsy (P < 0.01). *
      High testosterone levels were found in patients allocated to the low risk of
      progression group and inversely (P= 0.03). * In multivariate analysis, higher age
      and lower testosterone were related to higher D'Amico risk of progression.
      CONCLUSION: * Patients with PCa and lower testosterone levels have poor prognosis
      factors and higher tumour burden before treatment onset. These findings reinforce
      the idea that low testosterone levels pretreatment are related to a poor
      prognosis in PCa.

PMID- 22584032
TI  - Qualitative evaluation of a local coronary heart disease treatment pathway:
      practical implications and theoretical framework.
AB  - BACKGROUND: Coronary heart disease (CHD) is a common medical problem in general
      practice. Due to its chronic character, shared care of the patient between
      general practitioner (GP) and cardiologist (C) is required. In order to improve
      the cooperation between both medical specialists for patients with CHD, a local
      treatment pathway was developed. The objective of this study was first to
      evaluate GPs' opinions regarding the pathway and its practical implications, and
      secondly to suggest a theoretical framework of the findings by feeding the
      identified key factors influencing the pathway implementation into a multi
      dimensional model. METHODS: The evaluation of the pathway was conducted in a
      qualitative design on a sample of 12 pathway developers (8 GPs and 4
      cardiologists) and 4 pathway users (GPs). Face-to face interviews, which were
      aligned with previously conducted studies of the department and assumptions of
      the theory of planned behaviour (TPB), were performed following a semi-structured
      interview guideline. These were audio-taped, transcribed verbatim, coded, and
      analyzed according to the standards of qualitative content analysis. RESULTS: We
      identified 10 frequently mentioned key factors having an impact on the
      implementation success of the CHD treatment pathway. We thereby differentiated
      between pathway related (pathway content, effort, individual flexibility,
      ownership), behaviour related (previous behaviour, support), interaction related
      (patient, shared care/colleagues), and system related factors (context, health
      care system). The overall evaluation of the CHD pathway was positive, but did not
      automatically lead to a change of clinical behaviour as some GPs felt to have
      already acted as the pathway recommends. CONCLUSIONS: By providing an account of
      our experience creating and implementing an intersectoral care pathway for CHD,
      this study contributes to our knowledge of factors that may influence physicians'
      decisions regarding the use of a local treatment pathway. An improved adaptation
      of the pathway in daily practice might be best achieved by a combined
      implementation strategy addressing internal and external factors. A simple,
      direct adaptation regards the design of the pathway material (e.g. layout, PC
      version), or the embedding of the pathway in another programme, like a Disease
      Management Programme (DMP). In addition to these practical implications, we
      propose a theoretical framework to understand the key factors' influence on the
      pathway implementation, with the identified factors along the microlevel (pathway
      related factors), the mesolevel (interaction related factors), and system-
      related factors along the macrolevel.

PMID- 22584033
TI  - The University Munster model surgery system for orthognathic surgery. Part I--the
      idea behind.
AB  - BACKGROUND: We describe a procedure for diagnosis and planning for orthognathic
      surgery based on international standards. A special 2D planning based on lateral
      cephalograms (Axis Orbital Marker Lines System) realize a transmission to the SAM
      2P articulator (3D) by means of the Axis Orbital Plane. METHODS: Former
      intraoperative measurement of the average height of the LeFort I osteotomy plane
      relative to the molar occlusal plane allow to construct a virtual osteotomy plane
      in the lateral cephalogram. This is the basis for the development of the Axis
      Orbital Marker Lines System (AO-MLS). RESULTS: The AO-MLS is presented
      graphically, and in detail, with construction guidelines. The system could be
      integrated into various lateral cephalometric analysis- and surgical prediction
      schemes. It forms the basis for a standardized transfer of the 2D planning to the
      3D planning in the articulator, and vice versa. This procedure makes it possible
      to generate surgical planning protocols based on the model surgery, which
      represent the dislocations in the proximity of the real osteotomy planes.
      CONCLUSIONS: The Axis Orbital Marker Lines System (software component) in
      conjunction with the University Munster Model Surgery System (hardware system)
      increases the predictability of model operations in orthognathic surgery.

PMID- 22584035
TI  - Mycoplasma hominis in Cuban Trichomonas vaginalis isolates: association with
      parasite genetic polymorphism.
AB  - Trichomonas vaginalis can be naturally infected with intracellular Mycoplasma
      hominis. This bacterial infection may have implications for trichomonal virulence
      and disease pathogenesis. The objective of the study was to report the presence
      of M. hominis in Cuban T. vaginalis isolates and to describe the association
      between the phenotype M. hominis infected with RAPD genetic polymorphism of T.
      vaginalis. The Random Amplified Polymorphic DNA (RAPD) technique was used to
      determine genetic differences among 40 isolates of T. vaginalis using a panel of
      30 random primers and these genetic data were correlated with the infection of
      isolates with M. hominis. The trees drawn based on RAPD data showed no relations
      with metronidazole susceptibility and significantly association with the presence
      of M. hominis (P=0.043), which demonstrates the existence of concordance between
      the genetic relatedness and the presence of M. hominis in T. vaginalis isolates.
      This result could point to a predisposition of T. vaginalis for the bacterial
      enters and/or survival.

PMID- 22584034
TI  - Supplementation of highly concentrated beta-cryptoxanthin in a satsuma mandarin
      beverage improves adipocytokine profiles in obese Japanese women.
AB  - BACKGROUND: Serum beta-cryptoxanthin levels are lower in overweight subjects than
      in normal subjects. Abnormalities of adipocytokine profiles in obesity subjects
      have been reported. There are several reports that serum beta-cryptoxanthin
      levels in them were relatively lower than normal subjects. OBJECTIVE: We
      hypothesize that supplementation of highly concentrated beta-cryptoxanthin
      improves serum adipocytokine profiles in obese subjects. This study tested the
      association between beta-cryptoxanthin intake and serum adipocytokine levels.
      METHODS: An intervention study consisted of a 3-week long before-and-after
      controlled trial, where beta-cryptoxanthin (4.7 mg/day) was given to 17
      moderately obese postmenopausal women. RESULTS: The results indicated no
      significant changes in body weight or body mass index (BMI). Serum beta
      cryptoxanthin levels increased significantly by 4-fold. Serum high molecular
      weight (HMW)-adiponectin levels increased significantly, while serum plasminogen
      activator inhibitor (PAI)-1 levels decreased. CONCLUSIONS: We concluded that
      increasing the intake of beta-cryptoxanthin to approximately 4 mg per day for 3
      weeks may have beneficial effects on the serum adipocytokine status and
      consequently alleviate progression of metabolic syndrome.

PMID- 22584036
TI  - Alkane metathesis by tandem alkane-dehydrogenation-olefin-metathesis catalysis
      and related chemistry.
AB  - Methods for the conversion of both renewable and non-petroleum fossil carbon
      sources to transportation fuels that are both efficient and economically viable
      could greatly enhance global security and prosperity. Currently, the major route
      to convert natural gas and coal to liquids is Fischer-Tropsch catalysis, which is
      potentially applicable to any source of synthesis gas including biomass and
      nonconventional fossil carbon sources. The major desired products of Fischer
      Tropsch catalysis are n-alkanes that contain 9-19 carbons; they comprise a clean
      burning and high combustion quality diesel, jet, and marine fuel. However,
      Fischer-Tropsch catalysis also results in significant yields of the much less
      valuable C(3) to C(8)n-alkanes; these are also present in large quantities in oil
      and gas reserves (natural gas liquids) and can be produced from the direct
      reduction of carbohydrates. Therefore, methods that could disproportionate medium
      weight (C(3)-C(8)) n-alkanes into heavy and light n-alkanes offer great potential
      value as global demand for fuel increases and petroleum reserves decrease.  This
      Account describes systems that we have developed for alkane metathesis based on
      the tandem operation of catalysts for alkane dehydrogenation and olefin
      metathesis. As dehydrogenation catalysts, we used pincer-ligated iridium
      complexes, and we initially investigated Schrock-type Mo or W alkylidene
      complexes as olefin metathesis catalysts. The interoperability of the catalysts
      typically represents a major challenge in tandem catalysis. In our systems, the
      rate of alkane dehydrogenation generally limits the overall reaction rate,
      whereas the lifetime of the alkylidene complexes at the relatively high
      temperatures required to obtain practical dehydrogenation rates (ca. 125 -200 
      degrees C) limits the total turnover numbers. Accordingly, we have focused on the
      development and use of more active dehydrogenation catalysts and more stable
      olefin-metathesis catalysts. We have used thermally stable solid metal oxides as
      the olefin-metathesis catalysts. Both the pincer complexes and the alkylidene
      complexes have been supported on alumina via adsorption through basic para
      substituents. This process does not significantly affect catalyst activity, and
      in some cases it increases both the catalyst lifetime and the compatibility of
      the co-catalysts.  These molecular catalysts are the first systems that effect
      alkane metathesis with molecular-weight selectivity, particularly for the
      conversion of C(n)n-alkanes to C(2n-2)n-alkanes plus ethane. This molecular
      weight selectivity offers a critical advantage over the few previously reported
      alkane metathesis systems. We have studied the factors that determine molecular
      weight selectivity in depth, including the isomerization of the olefinic
      intermediates and the regioselectivity of the pincer-iridium catalyst for
      dehydrogenation at the terminal position of the n-alkane.  Our continuing work
      centers on the development of co-catalysts with improved interoperability,
      particularly olefin-metathesis catalysts that are more robust at high temperature
      and dehydrogenation catalysts that are more active at low temperature. We are
      also designing dehydrogenation catalysts based on metals other than iridium. Our
      ongoing mechanistic studies are focused on the apparently complex combination of
      factors that determine molecular-weight selectivity.

PMID- 22584037
TI  - A gray matter of taste: sound perception, music cognition, and Baumgarten's
      aesthetics.
AB  - Music is an ancient and ubiquitous form of human expression. One important
      component for which music is sought after is its aesthetic value, whose
      appreciation has typically been associated with largely learned, culturally
      determined factors, such as education, exposure, and social pressure. However,
      neuroscientific evidence shows that the aesthetic response to music is often
      associated with automatic, physically- and biologically-grounded events, such as
      shivers, chills, increased heart rate, and motor synchronization, suggesting the
      existence of an underlying biological platform upon which contextual factors may
      act. Drawing on philosophical notions and neuroscientific evidence, I argue that,
      although there is no denying that social and cultural context play a substantial
      role in shaping the aesthetic response to music, these act upon largely
      universal, biological mechanisms involved with neural processing. I propose that
      the simultaneous presence of culturally-influenced and biologically-determined
      contributions to the aesthetic response to music epitomizes Baumgarten's equation
      of sensory perception with taste. Taking the argument one step further, I suggest
      that the heavily embodied aesthetic response to music bridges the cleavage
      between the two discrepant meanings-the one referring to sensory perception, the
      other referring to judgments of taste-traditionally attributed to the word
      "aesthetics" in the sciences and the humanities.

PMID- 22584038
TI  - Surgical management of stem cell transplantation-related complications in
      children.
AB  - HSCT is an established treatment option for some children with life-threatening
      diseases, but complications remain a major cause of morbidity and mortality. This
      retrospective data analysis addresses the surgical issues of children with HSCT
      related complications. Between 2002 and 2008, HSCT was performed in 240 children
      for leukemias/lymphomas (n=135), solid tumors (n=59), immunodeficiencies (n=20),
      lipid storage diseases (n=10), autoimmune diseases (n=9), and others (n=7). HSCT
      related complications requiring surgery occurred in 24 cases (10%) and most often
      in the leukemias/lymphomas group (18/24 cases): HC (cystoscopic irrigation, n=7),
      pulmonary aspergilloses (resection, n=7), bone necroses (core decompression,
      n=3), GvHD bowel (colostomy/PEG, n=2), ICH (drainage, n=2), bilateral kidney
      abscess (nephrectomies/renal transplantation, n=1), aspergillosis of the
      maxillary sinus (decompression, n=1), and post-traumatic wound healing disorder
      (meshed skin transplantation, n=1). Survival was 50% in the group with surgery
      and 62% in the group without (p=0.275). Even though this difference was not
      statistically significant, surgical intervention should be encouraged in all
      cases to achieve favorable results.

PMID- 22584039
TI  - Vocal cord palsy after vincristine treatment in a child and the inefficacy of
      glutamic acid in the prevention of relapse: a case report.
AB  - INTRODUCTION: Vincristine is an antineoplastic drug with a well known efficacy
      for the treatment of acute lymphoblastic leukemia and many solid tumors. No more
      than 20 pediatric patients with vincristine-induced vocal cord palsy have been
      reported, and to the best of our knowledge this is the first case where glutamic
      acid was administered with the aim of preventing a relapse of laryngeal
      dysfunction. CASE PRESENTATION: The larynx paralysis presented with hoarseness
      and stridor in a Caucasian 18-month-old girl and spontaneously resolved in about
      a month. In order to administer a subsequent full dose of vincristine, our
      patient received oral glutamic acid whose efficacy against vincristine
      neurological side effects has been previously reported. CONCLUSIONS: Since in our
      patient the amino acid proved to be ineffective in the prevention of laryngeal
      paralysis relapse, we suggest that a dose reduction of vincristine should be
      preferred by oncologists as an initial approach after a case of drug-induced
      vocal cord palsy.

PMID- 22584040
TI  - A novel deformation method for fast simulation of biological tissue formed by
      fibers and fluid.
AB  - This paper presents a new approach to the simulation of soft tissues deformation
      suitable for real time computation, particularly intriguing for medical
      applications. The approach implements a quasi-static solution for elastic global
      deformations of objects filled with fluid and fibers, which can be a good
      approximation for biological tissues. It is based on the Pascal's principle and
      the conservation of volume. Large deformations that quickly change the whole
      shape of the object can be stably simulated in a small number of time steps. In
      our approach each pair of surface vertices is connected and defines an elastic
      fiber. The set of all the elastic fibers defines a mesh of an order of magnitude
      smaller than the volumetric meshes, allowing the simulation of complex objects
      with less computational effort. The proposed method was applied to study the
      effects of forces for deformation and displacement of soft geometrical objects
      (rod, sphere, etc.) in order to analyze the results on simple forms. Then a
      compression similar to the deformation obtained during a mammographic examination
      procedure is applied to a breast. A preliminary validation is done by comparing
      deformation result between our new method and real ex vivo bovine liver. The
      results of this comparison show a high degree of similarities between the
      experimental results and deformations calculated by our method. This new method
      is suited to isotropic or anisotropic elasticity and linear or nonlinear stress
      strain relationship. Finally, the results of the deformations were shown to be
      independent of the mesh discretization for our method.

PMID- 22584041
TI  - The company that words keep: comparing the statistical structure of child- versus
      adult-directed language.
AB  - Does child-directed language differ from adult-directed language in ways that
      might facilitate word learning? Associative structure (the probability that a
      word appears with its free associates), contextual diversity, word repetitions
      and frequency were compared longitudinally across six language corpora, with four
      corpora of language directed at children aged 1.0 to 5.0, and two adult-directed
      corpora representing spoken and written language. Statistics were adjusted
      relative to shuffled corpora. Child-directed language was found to be more
      associative, repetitive and consistent than adult-directed language. Moreover,
      these statistical properties of child-directed language better predicted word
      acquisition than the same statistics in adult-directed language. Word frequency
      and repetitions were the best predictors within word classes (nouns, verbs,
      adjectives and function words). For all word classes combined, associative
      structure, contextual diversity and word repetitions best predicted language
      acquisition. These results support the hypothesis that child-directed language is
      structured in ways that facilitate language acquisition.

PMID- 22584042
TI  - Silymarin improves the behavioural, biochemical and histoarchitecture alterations
      in focal ischemic rats: a comparative evaluation with piracetam and
      protocatachuic acid.
AB  - Comparative neuroprotective potential of silymarin, piracetam and protocatechuic
      acid ethyl ester (PCA) was evaluated in focal ischemic rats. Various
      pharmacological, biochemical (lipid peroxidation, reduced glutathione, catalase,
      nitrite content, brain water content) and behavioural (memory impairment, motor
      control, neurological score) including infarct size and histopathological
      alterations were evaluated. Silymarin (200mg/kg) and PCA treatment significantly
      improved behavioural, biochemical and histopathological changes, and reduced
      water content and infarct size. However, piracetam only improved behavioural and
      histopathological changes, reduced water content and infarct size. The findings
      indicate that silymarin exhibits neuroprotective activity better than PCA and
      piracetam in focal ischemia/reperfusion reflected by its better restoration of
      behavioural and antioxidant profile.

PMID- 22584043
TI  - Differential severity of anxiogenic effects resulting from a brief swim or
      underwater trauma in adolescent male rats.
AB  - Clinical studies have shown a link between early-life adversity and severity of
      adulthood responses to a traumatic stress event (post-traumatic stress disorder,
      PTSD). Despite a need for basic research, few rodent models are available to test
      the lasting impacts of early-life traumatic stressors. Underwater trauma (UWT)
      has been used previously to model traumatic stress; however, effects of this
      procedure have only been characterized in adulthood. Susceptibility of younger
      animals to physiological or psychological damage from a forced submersion
      procedure is unknown. A procedure involving swimming may be a stressful stimulus
      outside of the underwater component of the experience, as well. The acute effects
      of a 1-minute sham exposure (empty water tank), swim-only, and UWT (40s swim
      followed by 20s underwater) were compared in adolescent rats at postnatal day 37.
      No effects on blood oxygenation or lung tissue were observed. Stepwise decreases
      in open arm behavior were observed on the elevated plus maze (EPM) in swim-only
      rats, while UWT rats showed an immediate, lasting decrease in open arm behavior.
      UWT rats showed a significant decrease in basal corticosterone one week after
      trauma. These results show that while water immersion is a stressor, UWT causes a
      distinct syndrome of traumatic stress response in adolescent rats.

PMID- 22584044
TI  - Increased hospitalizations among sarcoidosis patients from 1998 to 2008: a
      population-based cohort study.
AB  - BACKGROUND: Diagnostic and treatment approaches for sarcoidosis have changed
      dramatically over the past decade. Yet, the most recent reports of trends in
      hospitalizations of sarcoidosis patients are over ten years old. The objectives
      of this study were to determine the incidence of sarcoidosis among hospitalized
      patients and to analyze recent trends and seasonality of hospitalizations in
      sarcoidosis patients. METHODS: We performed a retrospective cohort study of the
      Nationwide Inpatient Sample from 1998 through 2008. We identified all
      hospitalizations with a primary or secondary diagnosis of sarcoidosis (ICD-9-CM
      code 135). Incidence was modeled as a seasonal time series about a linear trend.
      RESULTS: Time series analysis of the monthly number of hospitalizations revealed
      a distinct positive linear trend. Over the study period, the number of
      hospitalized patients with sarcoidosis increased from 37,516 to 70,947 cases.
      Trends were most pronounced in patients older than 55 years (p < 0.0001), African
      Americans (p < 0.0001), females (p = 0.0289), and non-Medicaid populations (p <
      0.0001). Hospitalizations are seasonal with highest incidence in January through
      March. CONCLUSIONS: Hospitalizations among sarcoidosis patients have almost
      doubled during the past decade, with disproportionate rate increases in African
      Americans, women, and older patients. The rate also increases among patients with
      insurance other than Medicaid. This study indicates the need for heightened
      surveillance of sarcoidosis patients given the unknown consequences of evolving
      treatment approaches. Our results point to a need for research investigating risk
      factors for hospitalization, including medications, co-morbidities, demographics,
      and socioeconomic status.

PMID- 22584045
TI  - Effects of intra-mammary bacterial infection with coagulase negative
      staphylococci and stage of lactation on shedding of epithelial cells and
      infiltration of leukocytes into milk: comparison among cows, goats and sheep.
AB  - The effects of mammary gland bacterial infection and stage of lactation on
      leukocyte infiltration into the mammary gland were compared among cows, goats and
      sheep. Animals were at two stages of lactation: mid or late. In mid-lactation
      animals, bacterial-free glands and coagulase negative Staphylococcus (CNS)
      infected glands were compared. In late lactation only uninfected glands were
      studied. Of mid-lactation bacteria-free animals, goats had the highest number of
      leukocytes and % polymorphonuclears (PMNs), whereas sheep had the lowest and
      leukocytes number in cows were intermediate between sheep and goats. Based on
      %PMN, two cell clusters were found in sheep, which overlapped with the parallel
      cell clusters of cows and goats, but with a slightly higher number of leukocytes
      in each cell cluster. At late lactation, goats had higher values for %PMN and
      leukocyte numbers in comparison to cows, which had a similar cellular profile to
      sheep. The cellular immune response to CNS infection was similar for the three
      animal species, although the number of cells was different, while the basal cell
      level at mid-lactation and especially at the end of lactation was species
      specific.

PMID- 22584046
TI  - Prevalence of Chlamydophila psittaci infections in the eyes of cattle, buffaloes,
      sheep and goats in contact with a human population.
AB  - This work is an example of cooperation between veterinary and human medicine
      being fully complementary and at the same time, indispensable to improve our
      knowledge on animal chlamydiosis. This study investigated the existence of ocular
      chlamydiae and determined the prevalence of its presence, chlamydiosis, in
      asymptomatic and diseased farm animals and adjacent humans. Data were obtained by
      the omp2 gene family Chlamydiaceae-specific PCR. Two hundred cattle, buffaloes,
      sheep and goats and 44 human specimens were also examined. Conjunctival swabs
      from both the eyes were collected from all animals and humans using cotton swabs.
      Samples were tested for chlamydiae by Vero cells tissue culture, chicken embryo,
      modified Gimenez staining, direct fluorescein-conjugated monoclonal antibody
      staining (FA), immunoperoxidase, CFT and PCR. The PCR-RFLP revealed that
      Chlamydophila psittaci demonstrated in the conjunctival samples of cattle (68%
      asymptomatic and 88% diseased), of buffalo (68% asymptomatic and 72% diseased),
      of sheep (68% asymptomatic and 80% diseased), of goat (76% asymptomatic and 92%
      diseased) and of humans (77% asymptomatic and 82% diseased). The Cp. psittaci was
      the only chlamydiae demonstrated in all of the ocular conjunctival samples, which
      confirms the prevalence of Cp. psittaci in this population of animals and
      adjacent humans. Statistically, the animal species factor was calculated and was
      found to be of no significance. Yet, there appeared to be a significant
      difference in the percentage of animal that tested positive using the different
      methods. Detection of Cp. psittaci in most samples confirms the prevalence of Cp.
      psittaci in this population of animals and adjacent humans.

PMID- 22584047
TI  - Increased type II collagen cleavage by cathepsin K and collagenase activities
      with aging and osteoarthritis in human articular cartilage.
AB  - INTRODUCTION: The intra-helical cleavage of type II collagen by proteases,
      including collagenases and cathepsin K, is increased with aging and
      osteoarthritis (OA) in cartilage as determined by immunochemical assays. The
      distinct sites of collagen cleavage generated by collagenases and cathepsin K in
      healthy and OA human femoral condylar cartilages were identified and compared.
      METHODS: Fixed frozen cartilage sections were examined immunohistochemically,
      using antibodies that react with the collagenase-generated cleavage neoepitopes,
      C2C and C1,2C, and the primary cleavage neoepitope (C2K) generated in type II
      collagen by the action of cathepsin K and possibly by other proteases, but not by
      any collagenases studied to date. RESULTS: In most cases, the staining patterns
      for collagen cleavage were similar for all three epitopes: weak to moderate
      mainly pericellular staining in non-OA cartilage from younger individuals and
      stronger, more widespread staining in aging and OA cartilages that often extended
      from the superficial to the mid/deep zone of the tissue. In very degenerate OA
      specimens, with significant disruption of the articular surface, staining was
      distributed throughout most of the cartilage matrix. CONCLUSIONS: Cleavage of
      collagen by proteases usually arises pericellularly around chondrocytes at and
      near the articular surface, subsequently becoming more intense and extending
      progressively deeper into the cartilage with aging and OA. The close
      correspondence between the distributions of these products suggests that both
      collagenases and cathepsin K, and other proteases that may generate this distinct
      cathepsin K cleavage site, are usually active in the same sites in the
      degradation of type II collagen.

PMID- 22584048
TI  - Infant malnutrition predicts conduct problems in adolescents.
AB  - OBJECTIVES: The purpose of this study was to compare the prevalence of conduct
      problems in a well-documented sample of Barbadian adolescents malnourished as
      infants and a demographic comparison group and to determine the extent to which
      cognitive impairment and environmental  factors account for this association.
      METHODS: Behavioral symptoms were assessed using a 76-item self-report scale in
      56 Barbadian youth (11-17 years of age) with histories of protein-energy
      malnutrition (PEM) limited to the first year of life and 60 healthy  classmates.
      Group comparisons were carried out by longitudinal and cross-sectional multiple
      regression analyses at 3 time points in childhood and adolescence. RESULTS: Self
      reported conduct problems were more prevalent among previously malnourished youth
      (P < 0.01).  Childhood IQ and home environmental circumstances partially mediated
      the association with malnutrition. Teacher-reported classroom behaviors at
      earlier ages were significantly correlated with youth conduct problems,
      confirming the continuity of conduct problems through childhood and adolescence.
      DISCUSSION: Self-reported conduct problems are elevated in children and
      adolescents with histories of early childhood malnutrition. Later vulnerability
      to increased conduct problems appears to be mediated by the more proximal
      neurobehavioral effects of the malnutrition on cognitive  function and by adverse
      conditions in the early home environment.

PMID- 22584049
TI  - Vertebral fractures in patients with inflammatory bowel disease compared with a
      healthy population: a prospective case-control study.
AB  - BACKGROUND: A prospective study was performed to compare the prevalence of
      morphometric vertebral fractures (MVF) between patients with inflammatory bowel
      disease (IBD) and healthy subjects and to identify predictive factors of
      fracture. METHODS: A total of 107 patients with IBD (53 with Crohn's disease and
      54 with ulcerative colitis) and 51 healthy subjects participated in the study.
      Information about anthropometric parameters, toxins, previous fractures, and
      parameters related to this disease were evaluated. The index of vertebral
      deformity, bone mass density (BMD), and biochemical parameters were calculated.
      RESULTS: A total of 72 fractures were detected in 38.32% of patients with IBD,
      and 10 fractures were detected in 13.73% of healthy subjects; the risk of
      fracture in patients with IBD was higher than that in control subjects (OR, 4.03;
      95% CI, 1.652-9.847; p < 0.002). We found no correlation between fracture and BMD
      in patients with IBD (lumbar spine, r = -0.103, p = 0.17 and femoral neck, r = 
      0.138, p = 0.07). Corticosteroid treatment was not associated with prevalent
      vertebral fractures nor with taking corticosteroids (r = 0.135, p = 0.14) or the
      duration for which they were taken (r = 0.08, p = 0.38), whereas this
      relationship was present in the controls (r = -0.365, p = 0.01). In the
      multivariate analysis, none of the measured parameters were significantly
      predictive of fracture, only to manifested IBD. Hypovitaminosis D was observed in
      55.14% of patients with IBD. CONCLUSIONS: The prevalence of morphometric
      vertebral fractures is higher in patients with IBD than in the healthy
      population, without association with BMD or corticoid treatment. Simply having
      IBD was proven to be a predictive factor of fracture. We observed a high
      incidence of hypovitaminosis D in patients with IBD.

PMID- 22584050
TI  - X-linked inhibitor of apoptosis protein mediates neddylation by itself but does
      not function as a NEDD8-E3 ligase for caspase-7.
AB  - X-linked inhibitor of apoptosis protein (XIAP) is a potent antagonist of
      caspases, and functions as a ubiquitin-E3 ligase by itself and for caspases.
      Recently, NEDD8, a ubiquitin-like modifier, has been suggested to be used for
      modification of caspase-7 mediated by XIAP. However, it is not clear whether
      caspase-7 is a bona fide target for NEDD8. Here we showed that no neddylation of
      caspase-7 but that of XIAP itself was observed under the conditions in which
      caspase-7 was modified with ubiquitin. These results reveal that XIAP does not
      function as a NEDD8-E3 ligase for caspase-7 in vivo.

PMID- 22584051
TI  - Perspective: Dynamics of receptor tyrosine kinase signaling complexes.
AB  - Textbook descriptions of signal transduction complexes provide a static snapshot
      view of highly dynamic events. Despite enormous strides in identifying the key
      components of signaling complexes and the underlying mechanisms of signal
      transduction, our understanding of the dynamic behavior of these complexes has
      lagged behind. Using the example of receptor tyrosine kinases, this perspective
      takes a fresh look at the dynamics of the system and their potential impact on
      signal processing.

PMID- 22584052
TI  - Expression screening of 17q12-21 amplicon reveals GRB7 as an ERBB2-dependent
      oncogene.
AB  - Gene amplification is a major genetic alteration in human cancers. Amplicons,
      amplified genomic regions, are believed to contain "driver" genes responsible for
      tumorigenesis. However, the significance of co-amplified genes has not been
      extensively studied. We have established an integrated analysis system of
      amplicons using retrovirus-mediated gene transfer coupled with a human full
      length cDNA set. Applying this system to 17q12-21 amplicon observed in breast
      cancer, we identified GRB7 as a context-dependent oncogene, which modulates the
      ERBB2 signaling pathway through enhanced phosphorylation of ERBB2 and Akt. Our
      work provides an insight into the biological significance of gene amplification
      in human cancers.

PMID- 22584053
TI  - Interfacial water molecules in SH3 interactions: Getting the full picture on
      polyproline recognition by protein-protein interaction domains.
AB  - The recognition of proline-rich sequences by protein-protein interaction modules
      is essential for many cellular processes. Nonetheless, in spite of the wealth of
      structural and functional information collected over the last two decades,
      polyproline recognition is still not well understood. The patent inconsistency
      between the generally accepted description of SH3 interactions, based primarily
      on the stacking of hydrophobic surfaces, and their markedly exothermic character
      is a clear illustration of the higher complexity of these systems. Here we review
      the structural and thermodynamic evidence revealing the need for a revision of
      the current binding paradigm, incomplete and clearly insufficient for a full
      understanding of binding affinity and specificity, to include interfacial water
      molecules as universal and relevant elements in polyproline recognition.

PMID- 22584054
TI  - Drosophila Bicoid is a substrate of sumoylation and its activator function is
      subject to inhibition by this post-translational modification.
AB  - Bicoid (Bcd) is a Drosophila morphogenetic protein and a transcriptional
      activator. Genetic studies have suggested a role of sumoylation in Bcd function,
      but it is unknown how Bcd activity is affected specifically by its own
      sumoylation status. Here we show that Bcd is sumoylated in Drosophila cells. We
      identify a lysine residue of Bcd as the primary sumoylation site. Using a Bcd
      mutant defective in being sumoylated, we show that sumoylation of Bcd is
      inhibitory to its ability to activate transcription. We provide evidence
      suggesting that the SUMO moiety has an intrinsic inhibitory activity for the
      activator function of Bcd.

PMID- 22584055
TI  - A new twist to coiled coil.
AB  - Spectrin repeats have been largely considered as passive linkers or spacers with
      little functional role other than to convey flexibility to a protein. Whilst this
      is undoubtedly part of their function, it is by no means all. Whilst the overt
      structure of all spectrin repeats is a simple triple-helical coiled coil, the
      linkages between repeats and the surface properties of repeats vary widely.
      Spectrin repeats in different proteins can act as dimerisation interfaces,
      platforms for the recruitment of signalling molecules, and as a site for the
      interaction with cytoskeletal elements and even direct association with membrane
      lipids. In the case of dystrophin several of these functions overlap in the space
      of a few repeats.

PMID- 22584056
TI  - Protein translocation as a tool: The current rapamycin story.
AB  - In cell biology and pharmacology, small chemicals are mostly used as agonists and
      antagonists against receptors and enzymes. The immunosuppressant rapamycin can
      serve an entirely different purpose: if employed sensibly, it might function as
      an inducer of dimerization that is able to rapidly activate enzyme activity
      inside the intact cell. A number of very recent developments such as
      photoactivatable derivatives make rapamycin an even more attractive tool for
      basic science.

PMID- 22584057
TI  - Structural and functional consequences of mutating a proteobacteria-specific
      surface residue in the catalytic domain of Escherichia coli GluRS.
AB  - Nucleotides whose mutations seriously affect glutamylation efficiency are
      experimentally known for Escherichia coli tRNA(Glu). However, not much is known
      about functional hotspots on the complementary enzyme, glutamyl-tRNA synthetase
      (GluRS). From structural and functional studies on an Arg266Leu mutant of E. coli
      GluRS, we demonstrate that Arg266 is essential for efficient glutamylation of
      tRNA(Glu). Consistent with this result, we found that Arg266 is a conserved
      signature of proteobacterial GluRS. In contrast, most non-proteobacterial GluRS
      contain Leu, and never Arg, at this position. Our results imply a unique strategy
      of glutamylation of tRNA(Glu) in proteobacteria under phylum-specific
      evolutionary compulsions.

PMID- 22584058
TI  - Crystal structures of the state 1 conformations of the GTP-bound H-Ras protein
      and its oncogenic G12V and Q61L mutants.
AB  - GTP-bound Ras adopts two interconverting conformations, "inactive" state 1 and
      "active" state 2. However, the tertiary structure of wild-type (WT) state 1
      remains unsolved. Here we solve the state 1 crystal structures of H-Ras WT
      together with its oncogenic G12V and Q61L mutants. They assume open structures
      characterized by impaired interactions of both Thr-35 in switch I and Gly-60 in
      switch II with the gamma-phosphate of GTP and possess two surface pockets of
      mutually different shapes unseen in state 2, a potential target for selective
      inhibitor development. Furthermore, they provide a structural basis for the low
      GTPase activity of state 1.

PMID- 22584060
TI  - Dimeric structure of transmembrane domain of amyloid precursor protein in
      micellar environment.
AB  - Some pathogenic mutations associated with Alzheimer's disease are thought to
      affect structural-dynamic properties and the lateral dimerization of amyloid
      precursor protein (APP) in neuron membrane. Dimeric structure of APP
      transmembrane fragment Gln(686)-Lys(726) was determined in membrane-mimicking
      dodecylphosphocholine micelles using high-resolution NMR spectroscopy. The APP
      membrane-spanning alpha-helix Lys(699)-Lys(724) self-associates in a left-handed
      parallel dimer through extended heptad repeat motif
      I(702)X(3)M(706)X(2)G(709)X(3)A(713)X(2)I(716)X(3)I(720)X(2)I(723), whereas the
      juxtamembrane region Gln(686)-Val(695) constitutes the nascent helix, also
      sensing the dimerization. The dimerization mechanism of APP transmembrane domain
      has been described at atomic resolution for the first time and is important for
      understanding molecular events of APP sequential proteolytical cleavage resulting
      in amyloid-beta peptide.

PMID- 22584059
TI  - BRCT domains: A little more than kin, and less than kind.
AB  - BRCT domains are versatile protein modular domains found as single units or as
      multiple copies in more than 20 different proteins in the human genome.
      Interestingly, most BRCT-containing proteins function in the same biological
      process, the DNA damage response network, but show specificity in their molecular
      interactions. BRCT domains have been found to bind a wide array of ligands from
      proteins, phosphorylated linear motifs, and DNA. Here we discuss the biology of
      BRCT domains and how a domain-centric analysis can aid in the understanding of
      signal transduction events in the DNA damage response network.

PMID- 22584061
TI  - Islet engraftment and revascularization in clinical and experimental
      transplantation.
AB  - Proper revascularization after transplantation is assumed to be crucial for
      appropriate islet graft function. We developed a novel noninvasive imaging
      method, based on adenoviral transduction of islets with a hypoxia responsive
      reporter gene, for continuous in vivo monitoring of hypoxia  in islet grafts in a
      mouse model. In addition, morphological data were obtained from a deceased
      patient previously subject to intraportal transplantation. We detected only
      transient hypoxia in a minority of the animals transplanted. Importantly, a clear
      response to hypoxia was observed in  vitro after removal of the islet grafts on
      day 28 after transplantation. Also, the morphological data from the deceased
      patient demonstrated an extensive revascularization of the transplanted islets.
      In fact, no differences could be seen between native islets, in pancreas biopsies
      taken prior  to islet isolation, and transplanted islets regarding the number,
      distribution, and shape of the blood vessels. However, fewer small islets
      (diameter <39 um) were found in the liver compared to those found in native
      pancreases. Notably, an absolute majority of the transplanted islets  were found
      remaining within the venous lumen, in direct contact with the vessel wall. In
      conclusion, the results presented show less pronounced islet graft hypoxia after
      subcapsular transplantation than previously reported using more invasive methods.
      Also, formation of an extensive intraislet  capillary network, similar to that
      seen in native islets in the pancreas, was seen after clinical islet
      transplantation.

PMID- 22584062
TI  - Long term stability of paraoxonase-1 and high-density lipoprotein in human serum.
AB  - BACKGROUND: Paraoxonase-1 (PON1) is an enzyme with numerous functions and
      receives an increasing interest in clinical and epidemiological studies.
      Sometimes samples are stored for longer periods at a certain temperature.
      Therefore the stability of PON1 activity must be checked and retained upon
      storage for longer periods. RESULTS: In this study the stability of PON1 activity
      has been tested in human serum samples during storage up to 12 months at 3
      commonly used temperatures, -20 degrees C, -70 degrees C and -196 degrees C. It
      was found that the stability of the PON1 activity is constant during 12 months of
      storage at -70 degrees C and -196 degrees C. Storage at -20 degrees C resulted in
      a small but statistically significant decrease after 6 months to about 94% of its
      original value. Nonetheless, the rank order between the samples at T = 0 and 12
      months remained the same. The same temperature dependence was found for the
      associated high-density lipoprotein. CONCLUSIONS: It can be concluded that -70
      degrees C is the right temperature for storage to maintain the PON1 activity for
      at least one year. Storage at a lower temperature in liquid nitrogen (-196
      degrees C) is not necessary.

PMID- 22584063
TI  - Behaviour of Sotalia guianensis (van Beneden, 1864) (Cetacea, Delphinidae) and
      ethnoecological knowledge of artisanal fishermen from Canavieiras, Bahia, Brazil.
AB  - Artisanal fishermen, because of their direct and frequent contact with the
      aquatic environment, possess a wealth of knowledge about the natural history of
      the fauna of the region in which they live. This knowledge, both practical and
      theoretical, has been frequently utilized and integrated into academic research.
      Taking this into consideration, this study discusses the ethnoecological
      knowledge of artisanal fishermen from a community in Canavieiras, state of Bahia,
      Brazil regarding the Guiana dolphin (Sotalia guianensis), a typically costal
      member of the family Delphinidae that is little studied in this region. To this
      end, the behaviour of S. guianensis in Canavieiras was recorded over one year and
      the data obtained were compared with fishermen's reports. A total of 609 hours of
      behavioural observations of S. guianensis was conducted from a fixed point in
      alternate morning and afternoon sessions between October 2009 and September 2010.
      Observations were conducted from a pier (15 degrees 40'59"S and 38 degrees
      56'38"W) situated on the banks of the Pardo River estuary --the region's main
      river--at 5.5 m above water level. For ethnoecological data collection, semi
      structured interviews were carried out with 26 fishermen in May, June and
      September 2010 and January 2011 in the fishing community of Atalaia. Occasional
      boat expeditions were made with the fishermen to compare their reports with
      direct observations of the behaviour of S. guianensis. The results demonstrate
      that fishermen possess a body of knowledge about S. guianensis that describes in
      detail the main behavioural aspects of the species. They reported the presence of
      S. guianensis in the Pardo River estuary throughout the year and its gregarious
      behaviour. They cited a relationship between the movement of dolphins and tidal
      cycles, and their presence in the estuary associated with the search for food. In
      addition, the fishermen reported that numbers of infants in groups were
      proportional to group size. Behaviours described were compatible with the
      observations made in situ and with data found in the scientific literature,
      confirming the importance of traditional knowledge in complementing scientific
      data. One behaviour mentioned by the fishermen that had no equivalence in the
      scientific literature was confirmed in situ and, therefore, constitutes the first
      record for this species.

PMID- 22584064
TI  - Factor structure of emotional intelligence in schizophrenia.
AB  - Social cognition, which includes emotional intelligence, is impaired in
      schizophrenia. The Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) is a
      widely-used assessment of emotional intelligence, with a four-factor structure in
      healthy individual. However, a recent factor analysis in schizophrenia patients
      revealed a two-factor structure of the MSCEIT. The current study aimed to
      replicate this finding in a larger, more diverse, schizophrenia sample (n=194).
      Our findings revealed an identical two-factor structure as in the previously
      reported study, indicating that emotional intelligence is organized in a
      different manner in schizophrenia than it is in healthy controls.

PMID- 22584065
TI  - Global transcriptional analysis of psoriatic skin and blood confirms known
      disease-associated pathways and highlights novel genomic "hot spots" for
      differentially expressed genes.
AB  - There are major gaps in our knowledge regarding the exact mechanisms and genetic
      basis of psoriasis. To investigate the pathogenesis of psoriasis, gene expression
      in 10 skin (5 lesional, 5 nonlesional) and 11 blood (6 psoriatic, 5 nonpsoriatic)
      samples were examined using Affymetrix HG-U95A microarrays. We detected 535 (425
      upregulated, 110 downregulated) DEGs in lesional skin at 1% false discovery rate
      (FDR). Combining nine microarray studies comparing lesional and nonlesional
      psoriatic skin, 34.5% of dysregulated genes were overlapped in multiple studies.
      We further identified 20 skin and 2 blood associated transcriptional "hot spots"
      at specified genomic locations. At 5% FDR, 11.8% skin and 10.4% blood DEGs in our
      study mapped to one of the 12 PSORS loci. DEGs that overlap with PSORS loci may
      offer prioritized targets for downstream genetic fine mapping studies. Novel DEG
      "hot spots" may provide new targets for defining susceptibility loci in future
      studies.

PMID- 22584066
TI  - Next-generation sequencing-based transcriptome analysis of Cryptolaemus
      montrouzieri under insecticide stress reveals resistance-relevant genes in
      ladybirds.
AB  - As the most efficient natural enemy of mealybugs, the ladybird Cryptolaemus
      montrouzieri Mulsant plays an important role in integrated pest management. We
      report here a profiling analysis of C. montrouzieri under insecticide stress to
      gain a deeper view of insecticide resistance in ladybirds. For transcriptome
      sequencing, more than 26 million sequencing reads were produced. These reads were
      assembled into 38,369 non-redundant transcripts (mean size=453 nt). 23,248
      transcripts were annotated with their gene description. Using a tag-based DGE
      (Digital gene expression) system, over 5.7 million tags were sequenced in both
      the insecticide stress group and the control group, and mapped to 38,369
      transcripts. We obtained 993 genes that were significantly up- or down-regulated
      under insecticide stress in the ladybird transcriptome. These results can
      contribute to in-depth research into the molecular mechanisms of resistance and
      enhance our current understanding of the effects of insecticides on natural
      enemies.

PMID- 22584067
TI  - AncestrySNPminer: a bioinformatics tool to retrieve and develop ancestry
      informative SNP panels.
AB  - A wealth of genomic information is available in public and private databases.
      However, this information is underutilized for uncovering population specific and
      functionally relevant markers underlying complex human traits. Given the huge
      amount of SNP data available from the annotation of human genetic variation, data
      mining is a faster and cost effective approach for investigating the number of
      SNPs that are informative for ancestry. In this study, we present
      AncestrySNPminer, the first web-based bioinformatics tool specifically designed
      to retrieve Ancestry Informative Markers (AIMs) from genomic data sets and link
      these informative markers to genes and ontological annotation classes. The tool
      includes an automated and simple "scripting at the click of a button"
      functionality that enables researchers to perform various population genomics
      statistical analyses methods with user friendly querying and filtering of data
      sets across various populations through a single web interface. AncestrySNPminer
      can be freely accessed at
      https://research.cchmc.org/mershalab/AncestrySNPminer/login.php.

PMID- 22584068
TI  - CACG: a database for comparative analysis of conjoined genes.
AB  - A conjoined gene is defined as one formed at the time of transcription by
      combining at least part of one exon from each of two or more distinct genes that
      lie on the same chromosome, in the same or opposite orientation, which translate
      independently into different proteins. We comparatively studied the extent of
      conjoined genes in thirteen genomes by analyzing the public databases of
      expressed sequence tags and mRNA sequences using a set of computational tools
      designed to identify conjoined genes on the same DNA strand or opposite DNA
      strands of the same genomic locus. The CACG database, available at
      http://cgc.kribb.re.kr/map/, includes a number of conjoined genes (7131-human, 2
      chimpanzee, 5-orangutan, 57-chicken, 4-rhesus monkey, 651-cow, 27-dog, 2512
      mouse, 263-rat, 1482-zebrafish, 5-horse, 29-sheep, and 8-medaka) and is very
      effective and easy to use to analyze the evolutionary process of conjoined genes
      when comparing different species.

PMID- 22584069
TI  - Association of common variations of 8q24 with the risk of prostate cancer in
      Koreans and a review of the Asian population.

PMID- 22584070
TI  - Highly-conformal intensity-modulated radiotherapy reduced toxicity without
      jeopardizing outcome in patients with paranasal sinus cancer treated by surgery
      and radiotherapy or (chemo)radiation.
AB  - OBJECTIVES: To report oncologic outcomes of patients with paranasal sinus cancer
      (PNSC) treated by surgery and radiotherapy or (chemo)radiation and to investigate
      the impact of improving the radiation technique on outcomes and toxicity.
      MATERIALS AND METHODS: Between 1999 and 2010, 82 consecutive patients with PNSC
      were treated by surgery and radiotherapy or by definitive (chemo)radiation. Three
      dimensional conformal (3DCRT) or highly-conformal intensity-modulated RT (IMRT)
      was used. Endpoints were local control (LC), regional control (RC), disease-free
      (DFS), cause-specific (CSS), and overall survival (OS), late toxicity, and
      quality-of-life (QoL). RESULTS: After median follow-up of 51 months, the 5-year
      actuarial rates of LC, RC, DFS, CSS, and OS were 74%, 94%, 56%, 64%, and 54%,
      respectively. Grade >= 2 late toxicity at 5-years was 28%. High T-stage and
      perineural invasion were significantly associated with poor LC and RT-technique
      with late toxicity. Late toxicity was significantly lowered using IMRT, compared
      to 3DCRT (17% vs. 52%, p<0.0001). Visual preservation were significantly improved
      using IMRT (88% and 65%, respectively, p=0.01). LC-rate was also improved by IMRT
      (80% vs. 64%, respectively, p=0.2). QoL-scores deteriorated during and shortly
      after treatment but returned in almost all scales to baseline levels within 3-12
      months. CONCLUSIONS: Surgery and radiotherapy or definitive (chemo)radiation
      resulted in good LC rates but with high rate of late side-effects. However, late
      toxicity and permanent visual impairment were significantly decreased by using
      highly-conformal IMRT without jeopardizing outcome. The improvements in the
      therapeutic ratio achieved by using IMRT would allow dose escalation of RT to
      further improve outcomes.

PMID- 22584072
TI  - Acute-onset severe gastrointestinal tract hemorrhage in a postoperative patient
      taking rivaroxaban after total hip arthroplasty: a case report.
AB  - INTRODUCTION: Rivaroxaban, a new oral anticoagulant, is currently licensed for
      use in patients undergoing orthopedic surgery. It is more efficacious than other
      anticoagulants such as low molecular weight heparin and does not require daily
      monitoring. It has also been shown to be efficacious in patients with venous
      thromboembolism and acute coronary syndrome. Although hemorrhage is a known side
      effect of this new anticoagulant, we could find no case reports in the literature
      of patients suffering severe hemorrhage whilst taking rivaroxaban. Thus, we
      describe the first case of potentially fatal hemorrhage in a patient taking
      rivaroxaban. CASE PRESENTATION: We report the case of a 58-year-old Caucasian man
      with acute-onset severe per rectal bleeding who had undergone total hip
      arthroplasty four weeks prior to the onset of symptoms and was taking rivaroxaban
      in the postoperative period. Rivaroxaban was discontinued immediately but, having
      required nine units of packed red blood cells in a peripheral hospital due to a
      rapidly decreasing hemoglobin level, our patient was transferred to our tertiary
      referral center where he required a further eight units of packed red blood cells
      over a 48-hour period to manage his ongoing hemorrhage and maintain hemodynamic
      stability. No source of bleeding was found on computed tomography angiography and
      our patient's condition improved over the following 48 hours with cessation of
      the hemorrhage. Our patient was discharged home well several days later. A follow
      up colonoscopy one week after his discharge was normal. CONCLUSION: Although
      advantageous with regard to its oral availability and ongoing use without the
      need for daily monitoring, rivaroxaban does not come without rare but severe side
      effects. When severe per rectal bleeding occurs in a patient taking rivaroxaban,
      discontinuation of the offending agent and aggressive hematological replacement
      are the mainstays of treatment, especially when no source of bleeding can be
      found. This case, as the first to describe severe hemorrhage and rivaroxaban,
      serves as a reminder to those prescribing the medicine that they must inform the
      patient of the risk of such a serious side effect and the need for urgent medical
      attention if it occurs.

PMID- 22584071
TI  - Effect of foster care on language learning at eight years: findings from the
      Bucharest Early Intervention Project.
AB  - This study reports on language outcomes at eight years from the Bucharest Early
      Intervention Project, a randomized controlled study of foster care. We previously
      have shown that children placed in foster care by age two have substantially
      stronger preschool language outcomes than children placed later and children
      remaining in institutional care. One hundred and five children participated in
      the current study, fifty-four originally assigned to foster care and fifty-one to
      continued institutional care. Even though current placements varied, children
      originally in foster care had longer sentences and stronger sentence repetition
      and written word identification. Children placed in foster care by age two had
      significant advantages in word identification and nonword repetition; children
      placed by age 1 ; 3 performed equivalently to community peers. The results show
      the continuing adverse effects of early poor institutional care on later language
      development and the key importance of age of placement in a more optimal
      environment.

PMID- 22584073
TI  - Myocardial infarction in the young.

PMID- 22584074
TI  - Letter in response to Andrea K.Y. Lee et al. "normalcy rate of computed
      tomographic coronary angiography".

PMID- 22584075
TI  - A meta-analysis of effects of prosthesis-patient mismatch after aortic valve
      replacement on late mortality.

PMID- 22584076
TI  - Protective effects of grape seed extract against oxidative and nitrative damage
      of plasma proteins.
AB  - Oxidative stress, vascular inflammation, endothelial dysfunction plays a crucial
      role in the pathogenesis of cardiovascular diseases. The aim of our in vitro
      study was to examine the antioxidative properties of grape seed extract, and its
      potential protective effect on the haemostatic function of human fibrinogen under
      oxidative stress conditions, induced by peroxynitrite (100 MUM). The
      preincubation of plasma with the tested extract (0.5-50 MUg/ml or 0.5-300 MUg/ml)
      reduced the formation of 3-nitrotyrosine and diminished oxidation of thiol groups
      in plasma proteins. The low concentrations (0.5-50 MUg/ml) of grape seed extract
      also decreased the level of carbonyl groups, however at higher concentrations
      (100-300 MUg/ml) this effect was not observed. Furthermore, grape seed extract
      counteracted the inhibitory effect of peroxynitrite on human plasma clotting. The
      results obtained in this study indicate that components of the grape seed extract
      posses antioxidative properties and may be promising substances for the creation
      of new dietary supplements.

PMID- 22584077
TI  - Crystallographic portrayal of different conformational states of a Lys49
      phospholipase A2 homologue: insights into structural determinants for myotoxicity
      and dimeric configuration.
AB  - Catalytically inactive phospholipase A(2) (PLA(2)) homologues play key roles in
      the pathogenesis induced by snake envenomation, causing extensive tissue damage
      via a mechanism still unknown. Although, the amino acid residues directly
      involved in catalysis are conserved, the substitution of Asp49 by Arg/Lys/Gln or
      Ser prevents the binding of the essential calcium ion and hence these proteins
      are incapable of hydrolyzing phospholipids. In this work, the crystal structure
      of a Lys49-PLA(2) homologue from Bothrops brazili (MTX-II) was solved in two
      conformational states: (a) native, with Lys49 singly coordinated by the backbone
      oxygen atom of Val31 and (b) complexed with tetraethylene glycol (TTEG).
      Interestingly, the TTEG molecule was observed in two different coordination cages
      depending on the orientation of the nominal calcium-binding loop and of the
      residue Lys49. These structural observations indicate a direct role for the
      residue Lys49 in the functioning of a catalytically inactive PLA(2) homologue
      suggesting a contribution of the active site-like region in the expression of
      pharmacological effects such as myotoxicity and edema formation. Despite the
      several crystal structures of Lys49-PLA(2) homologues already determined, their
      biological assembly remains controversial with two possible conformations. The
      extended dimer with the hydrophobic channel exposed to the solvent and the
      compact dimer in which the active site-like region is occluded by the dimeric
      interface. In the MTX-II crystal packing analysis was found only the extended
      dimer as a possible stable quaternary arrangement.

PMID- 22584078
TI  - Structural effect of the L16Q, K50E, and R53P mutations on homeodomain of
      pituitary homeobox protein 2.
AB  - The transcription factor pituitary homeobox protein 2 (PITX2) is involved in
      genetic control of development. Mutations in PITX2, most in the homeodomain,
      cause the autosomal-dominant disorder Rieger syndrome. The mutants L16Q, K50E and
      R53P destabilize the structure and disrupt DNA-binding activity. The biological
      functions of these mutants have been characterized but not the structural basis
      behind the loss of DNA-binding activity. We performed multiple molecular dynamics
      simulations at 37 degrees C to investigate the structural and dynamic effects of
      the 3 PITX2 homeodomain mutants. Compared with the wild type (WT), the L16Q
      mutant induces a kink in the alpha3 helix, which is stabilized by the hydrogen
      bond of Q21-R59. The disruption in backbone hydrogen bonds of V47-N51 and W48-R52
      leads to a kink formation in the alpha3 helix of K50E. The R53P mutant alters the
      relative orientation of helices, which is apparently stabilized by the formation
      of new hydrogen bonds of T38-Q11, T38-Q12, T38-R2, N39-R2, L40-Q1, L40-R2, and
      T41-Q4. The hydrophobic core residues F8, L13, L40 and V45 change their positions
      in all mutants to break the hydrophobic core. Thus, changes in helical
      orientations and hydrophobic core cause rearrangement of the DNA-binding surface
      and disrupt DNA-binding activity in the mutants. The structural and molecular
      dynamics properties of 3 PITX2 homeodomain mutants differ from those of the WT,
      especially in formation of a kink in the recognition helix, change in the packing
      of helices and disruption of the hydrophobic core. This structural basis for the
      loss of DNA-binding activity for these polymorphisms may help in understanding
      the effect of mutations on other homeodomains with other diseases.

PMID- 22584079
TI  - Optimization on condition of glycyrrhetinic acid liposome by RSM and the research
      of its immunological activity.
AB  - The aim of this study is to prepare glycyrrhetinic acid liposome (GAL) and
      optimize the preparation condition and to investigate further whether liposome
      could promote the immunological activity of glycyrrhetinic acid (GA). GAL was
      prepared using a film-dispersion method and the preparation conditions of GAL
      were optimized with response surface methodology (RSM). Moreover, GAL prepared
      under the optimal preparation conditions was added into chicken's T and B
      lymphocytes in vitro. The optimal preparation conditions for GAL by response
      surface methodology was as follows: ratio 9:1, soybean phospholipid cholesterol
      (w/w) 2.5:1 and water bath temperature 31  degrees C. Under these conditions, the
      experimental encapsulation efficiency of GAL was 83.46 +/- 0.55%, which was close
      with the predicted value. Therefore, the optimized preparation condition is very
      reliable. The results showed that GAL could significantly promote T and B
      lymphocytes proliferation singly or synergistically with PHA and LPS and the
      concentration of immunoglobulins G (IgG) and immunoglobulins M (IgM). These
      results indicated that liposome could significantly improve the immunological
      activity of GA and drug action of GA. GAL demonstrates the significant
      immunological activity, which provides the theoretical basis for the further
      experiment in vivo.

PMID- 22584080
TI  - Endoscopic ultrasound criteria to predict the need for intervention in pancreatic
      necrosis.
AB  - BACKGROUND: The natural course and treatment strategies for asymptomatic or
      oligosymptomatic pancreatic necrosis are still poorly defined. The aim of this
      retrospective study was to establish criteria for the need of intervention in
      patients with pancreatic necrosis. METHODS: A total of 31 consecutive patients
      (18 male, median age 58 yrs.) diagnosed with pancreatic necrosis by endoscopic
      ultrasound, in whom a decision for initial conservative treatment was made, were
      followed for the need of interventions such as endoscopic or surgical
      intervention, or death. RESULTS: After a median follow-up of 243 days, 21
      patients remained well without intervention and in 10 patients an endpoint event
      occurred. In a multivariate logistic regression analysis of the clinical and
      endosonographic parameters, liquid content was the single independent predictor
      for intervention (p = 0.0006). The presence of high liquid content in the
      pancreatic necrosis resulted in a 64% predicted endpoint risk as compared to 2%
      for solid necrosis. CONCLUSIONS: Pancreatic necrotic cavities with high liquid
      content are associated with a high risk of complications. Therefore, close
      clinical monitoring is needed and early elective intervention might be considered
      in these patients.

PMID- 22584081
TI  - Risk of melanoma and nonmelanoma skin cancer among patients with inflammatory
      bowel disease.
AB  - BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) are at risk for
      certain malignancies. We aimed to determine the risk of melanoma and nonmelanoma
      skin cancer (NMSC) in patients with IBD and how medications affect these risks.
      METHODS: We performed retrospective cohort and nested case-control studies using
      administrative data from the LifeLink Health Plan Claims Database from 1997 to
      2009. The cohort comprised 108,579 patients with IBD, and each was matched to 4
      individuals without IBD. The risk of melanoma and NMSC was evaluated by incidence
      rate ratio (IRR) and by adjusted Cox proportional hazard ratio (HR) modeling. In
      nested case-control studies, patients with melanoma or NMSC were matched to 4
      patients with IBD without melanoma or NMSC. Conditional logistic regression was
      used to determine associations between medications and both skin cancers.
      RESULTS: In the cohort, IBD was associated with an increased incidence of
      melanoma (IRR, 1.29; 95% confidence interval [CI], 1.09-1.53). Risk was greatest
      among individuals with Crohn's disease (IRR, 1.45; 95% CI, 1.13-1.85; adjusted
      HR, 1.28; 95% CI, 1.00-1.64). The incidence of NMSC also increased among patients
      with IBD (IRR, 1.46; 95% CI, 1.40-1.53) and was greatest among those with CD
      (IRR, 1.64; 95% CI, 1.54-1.74). In the nested case-control studies, therapy with
      biologics increased the risk of melanoma (odds ratio [OR], 1.88; 95% CI, 1.08
      3.29). Patients who had been treated with thiopurines had an increased risk of
      NMSC (OR, 1.85; 95% CI, 1.66-2.05). CONCLUSIONS: Immunosuppression increases the
      risk of melanoma and NMSC among patients with IBD. The risk of melanoma is
      increased by use of biologics, and the risk of NMSC is increased by use of
      thiopurines. Patients with IBD should be counseled and monitored for skin cancer.

PMID- 22584082
TI  - A framework for identifying distinct multipollutant profiles in air pollution
      data.
AB  - BACKGROUND: The importance of describing, understanding and regulating multi
      pollutant mixtures has been highlighted by the US National Academy of Science and
      the Environmental Protection Agency. Furthering our understanding of the health
      effects associated with exposure to mixtures of pollutants will lead to the
      development of new multi-pollutant National Air Quality Standards. OBJECTIVES:
      Introduce a framework within which diagnostic methods that are based on our
      understanding of air pollution mixtures are used to validate the distinct air
      pollutant mixtures identified using cluster analysis. METHODS: Six years of daily
      gaseous and particulate air pollution data collected in Boston, MA were
      classified solely on their concentration profiles. Classification was performed
      using k-means partitioning and hierarchical clustering. Diagnostic strategies
      were developed to identify the most optimal clustering. RESULTS: The optimal
      solution used k-means analysis and contained five distinct groups of days.
      Pollutant concentrations and elemental ratios were computed in order to
      characterize the differences between clusters. Time-series regression confirmed
      that the groups differed in their chemical compositions. The mean values of
      meteorological parameters were estimated for each group and air mass origin
      between clusters was examined using back-trajectory analysis. This allowed us to
      link the distinct physico-chemical characteristics of each cluster to
      characteristic weather patterns and show that different clusters were associated
      with distinct air mass origins. CONCLUSIONS: This analysis yielded a solution
      that was robust to outlier points and interpretable based on chemical, physical
      and meteorological characteristics. This novel method provides an exciting tool
      with which to identify and further investigate multi-pollutant mixtures and link
      them directly to health effects studies.

PMID- 22584083
TI  - Elevated levels of fibrinogen-derived endogenous citrullinated peptides in
      synovial fluid of rheumatoid arthritis patients.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune disease characterized by
      inflammation of the joints and the presence of autoantibodies directed against
      proteins containing the non-standard arginine-derived amino acid citrulline. The
      protein fibrinogen, which has an essential role in blood clotting, is one of the
      most prominent citrullinated autoantigens in RA, particularly because it can be
      found in the inflamed tissue of affected joints. Here, we set out to analyze the
      presence of citrullinated endogenous peptides in the synovial fluid of RA and
      arthritic control patients. METHODS: Endogenous peptides were isolated from the
      synovial fluid of RA patients and controls by filtration and solid phase
      extraction. The peptides were identified and quantified using high-resolution
      liquid chromatography-mass spectrometry. RESULTS: Our data reveal that the
      synovial fluid of RA patients contains soluble endogenous peptides, derived from
      fibrinogen, containing significant amounts of citrulline residues and, in some
      cases, also phosphorylated serine. Several citrullinated peptides are found to be
      more abundantly present in the synovial fluid of RA patients compared to patients
      suffering from other inflammatory diseases affecting the joints. CONCLUSIONS: The
      increased presence of citrullinated peptides in RA patients points toward a
      possible specific role of these peptides in the immune response at the basis of
      the recognition of citrullinated peptides and proteins by RA patient
      autoantibodies.

PMID- 22584084
TI  - The effect of physical loading on calcaneus quantitative ultrasound measurement:
      a cross-section study.
AB  - BACKGROUND: Physical loading leads to a deformation of bone microstructure and
      may influence quantitative ultrasound (QUS) parameters. This study aims at
      evaluating the effect of physical loading on bone QUS measurement, and further,
      on the potential of diagnosing osteoporosis using QUS method under physical
      loading condition. METHODS: 16 healthy young females (control group) and 45
      postmenopausal women (divided into 3 groups according to the years since
      menopause (YSM)) were studied. QUS parameters were measured at calcaneus under
      self-weight loading (standing) and no loading (sitting) conditions. Weight
      normalized QUS parameter (QUS parameter measured under loading condition divided
      by the weight of the subject) was proposed to evaluate the influence of loading.
      T-test, One-Way analysis of variance (one way ANOVA) and receiver operating
      characteristic (ROC) analysis were applied for analysis. RESULTS: In QUS
      parameters, mainly normalized broadband ultrasound attenuation (nBUA), measured
      with loading significantly differed from those measured without loading (p <
      0.05). The relative changes of weight-normalized QUS parameters on postmenopausal
      women with respect to premenopausal women under loading condition were larger
      than those on traditional QUS parameters measured without loading. In ROC
      analysis, weight-normalized QUS parameters showed their stronger discriminatory
      ability for menopause. CONCLUSIONS: Physical loading substantially influenced
      bone QUS measurement (mainly nBUA). Weight-normalized QUS parameters can
      discriminate menopause more effectively. By considering the high relationship
      between menopause and osteoporosis, an inference was drawn that adding physical
      loading during measurement may be a probable way to improve the QUS based
      osteoporosis diagnosis.

PMID- 22584085
TI  - High-density lipoprotein subclass and particle size in coronary heart disease
      patients with or without diabetes.
AB  - BACKGROUND: A higher prevalence of coronary heart disease (CHD) in people with
      diabetes. We investigated the high-density lipoprotein (HDL) subclass profiles
      and alterations of particle size in CHD patients with diabetes or without
      diabetes. METHODS: Plasma HDL subclasses were quantified in CHD by 1-dimensional
      gel electrophoresis coupled with immunodetection. RESULTS: Although the particle
      size of HDL tend to small, the mean levels of low density lipoprotein
      cholesterol(LDL-C) and total cholesterol (TC) have achieved normal or desirable
      for CHD patients with or without diabetes who administered statins therapy.
      Fasting plasma glucose (FPG), triglyceride (TG), TC, LDL-C concentrations, and
      HDL3 (HDL(3b) and (3a)) contents along with Gensini Score were significantly
      higher; but those of HDL-C, HDL(2b+prebeta2), and HDL(2a) were significantly
      lower in CHD patients with diabetes versus CHD patients without diabetes; The
      prebeta1-HDL contents did not differ significantly between these groups.
      Multivariate regression analysis revealed that Gensini Score was significantly
      and independently predicted by HDL(2a), and HDL(2b+prebeta2). CONCLUSIONS: The
      abnormality of HDL subpopulations distribution and particle size may contribute
      to CHD risk in diabetes patients. The HDL subclasses distribution may help in
      severity of coronary artery and risk stratification, especially in CHD patients
      with therapeutic LDL, TG and HDL levels.

PMID- 22584086
TI  - Comparison of 4 recruiting strategies in a smoking cessation trial.
AB  - OBJECTIVES: To compare 4 online and off-line recruiting methods. METHODS: Young
      adult smokers (n=3353) were recruited to a trial comparing smoking cessation
      services with an online health risk assessment (HRA), online ads, offline
      materials, and quit-line screening. RESULTS: Online ads (n=1426; $41.35) and off
      line materials recruited the most smokers (n=1341; $56.23) for the lowest cost.
      Quitline screening was more expensive (n=189; $132.22), but enrollees used
      cessation services the most (34%-82%). Online HRA was least successful and most 
      costly (n=397; $630.85) but had the highest follow-up (45%-55%). CONCLUSIONS:
      Online ads and off-line materials were most effective and cost-effective methods.

PMID- 22584087
TI  - Developing an oropharyngeal cancer (OPC) knowledge and behaviors survey.
AB  - OBJECTIVES: To use the community participation research model to (1) develop a
      survey assessing knowledge about mouth and throat cancer and (2) field test and
      establish test-retest reliability with newly developed instrument. METHODS:
      Cognitive interviews with primarily  rural African American adults to assess
      their perception and interpretation of survey items. Test-retest reliability was
      established with a racially diverse rural population. RESULTS: Test-retest
      reliabilities ranged from .79 to .40 for screening awareness and .74 to .19 for
      knowledge.  Coefficients increased for composite scores. CONCLUSION: Community
      participation methodology provided a culturally appropriate survey instrument
      that demonstrated acceptable levels of reliability.

PMID- 22584089
TI  - African American smokers' intention to use pharmacotherapy for cessation.
AB  - OBJECTIVES: To use the theory of planned behavior to identify predictors of
      intentions to use cessation aids when quitting smoking. METHODS: African American
      smokers completed a survey to assess intentions, attitudes, and normative and
      control beliefs regarding the use  of smoking cessation aids. RESULTS:
      Participants held mildly positive attitudes regarding the use of cessation aids.
      Beliefs related to the utility of aids, support of referents, and accessibility
      of a doctor were most strongly associated with intention to use cessation aids.
      CONCLUSIONS: African American smokers may be amenable to the use of cessation
      aids, and specific beliefs may be targets for intervention.

PMID- 22584088
TI  - Understanding recovery barriers: youth perceptions about substance use relapse.
AB  - OBJECTIVE: To qualitatively explore how treatment-involved youth retrospectively
      contextualize relapse from substance use. METHODS: Fourteen focus groups were
      conducted with 118 youth (78.3% male; 66.1% Latino) enrolled in participating
      substance abuse treatment programs  (4 young adult and 10 adolescent) throughout
      Los Angeles County. Transcripts were analyzed for relapse perception themes.
      RESULTS: Dominant relapse themes include emotional reasons (90%), life stressors
      (85%), cognitive factors (75%), socialization processes (65%), and environmental 
      issues (55%). CONCLUSIONS: Youth perceptions about relapse during treatment
      should be used to better inform clinical approaches and shape early-intervention
      recovery agendas for substance-abusing youth.

PMID- 22584090
TI  - Influence of patients' coronary artery calcium on subsequent medication use
      patterns.
AB  - OBJECTIVES: To determine whether information on the presence and extent of
      coronary artery calcium (CAC) is associated with the likelihood of physicians'
      prescribing preventive therapies. METHOD: In a longitudinal design, asymptomatic
      participants (N=510) were evaluated  by computed tomography for CAC. Changes to
      medications were at the discretion of the patient's primary care provider, who
      received the CT report. RESULTS: In multivariable analysis, the likelihood of
      patients reporting that their primary care physician prescribed preventive
      therapies  was significantly associated with the presence and extent of CAC.
      CONCLUSIONS: This study suggests that physicians' prescribing practices are
      influenced by patients' CAC scores obtained via CT.

PMID- 22584091
TI  - Subjective social status predicts smoking abstinence among light smokers.
AB  - OBJECTIVES: To determine if community subjective social status (SSS) predicted
      smoking abstinence through 26 weeks postrandomization among 755 African American
      light smokers of low SES (socioeconomic status). METHODS: Participants were
      enrolled in a double-blind, placebo-controlled,  randomized clinical trial, which
      examined the efficacy of nicotine gum and counseling for smoking cessation.
      RESULTS: Results indicated that SSS predicted smoking abstinence over time
      [P=.046; odds ratio (OR) =1.075 (1.001-1.155)] after adjusting for covariates.
      CONCLUSIONS: Further research is needed to understand the effects of community
      SSS on smoking cessation among heavy smokers and other ethnic groups.

PMID- 22584092
TI  - Descriptive assessment of exercise program on fitness and correlates of
      participation.
AB  - OBJECTIVE: To assess health-related fitness, physical activity correlates, and
      completion of a half-marathon using a 3-day training program in a college
      community. METHODS: 26 volunteers participated in a 20-week, half-marathon
      training program. RESULTS: All participants  completed the half-marathon.
      Positive changes in health-related fitness and psychological correlates
      associated with future exercise participation were observed. CONCLUSIONS:
      Incorporating strategies that address physical activity correlates and barriers
      may increase adherence to a  program with a challenging goal such as training for
      a half-marathon. A low-frequency program was sufficient for increasing health
      related fitness and psychological factors related to exercise participation of
      campus community.

PMID- 22584093
TI  - Small retailer perspectives of the 2009 Women, Infants and Children Program food
      package changes.
AB  - OBJECTIVE: To understand vendor perspectives regarding changes made in 2009 to
      the Special Supplemental Nutrition Program for Women, Infant, and Children (WIC)
      food package. METHODS: Fifty-two in-depth, qualitative interviews with owners or
      managers of small stores in  8 urban areas across 7 states conducted 6-12 months
      after the changes. RESULTS: Store owners experienced implementation challenges,
      but felt the changes increased the number of customers, sales, and profits.
      CONCLUSION: This research provides vendor perspectives on the 2009 WIC  policy
      changes and may enhance policy implementation directed at increasing healthy food
      availability, particularly in urban communities.

PMID- 22584094
TI  - Public support toward tobacco control: consumer responsiveness and policy
      planning.
AB  - OBJECTIVES: To explore individual differences in support toward antismoking
      policies by investigating psychosocial, socioeconomic, and demographic
      characteristics; smoking restrictions; smoking status; and individually perceived
      cigarette price. METHODS: The empirical  analysis uses data from a random sample
      of 680 consumers and employs a bivariate semiordered probit model. RESULTS:
      Consumer responsiveness shows strong association with optimistic bias, perceived
      positive and negative consequences of smoking, health status, and family smoking
      patterns.  Smoking status, gender, age, and occupation also affect antismoking
      policy support. CONCLUSIONS: Public support toward tobacco control reflects
      potential smoking acceptance and social norms, confirming policy effectiveness
      and current needs for demarketing tobacco use.

PMID- 22584095
TI  - Perceived risk and quitting behaviors: results from the ITC 4-country survey.
AB  - OBJECTIVE: To rigorously test the relation between perceived risk (i.e., belief
      about the likelihood of harm) and quitting smoking. METHODS: Data from a
      longitudinal study with a nonrestrictive sample of smokers (N = 4307) from the
      United States, Canada, the United Kingdom, and Australia were examined to predict
      quitting behaviors at 8-12 months. RESULTS: Perceived risk predicted plans to
      quit, quit attempts, and, to some extent, sustained quitting. The relation was
      stronger for relatively simple (e.g., plans to quit) than for complex behaviors
      (e.g., sustained quitting). CONCLUSION: Perceived risk plays a significant role
      in predicting quitting smoking, more so for relatively simple behaviors.

PMID- 22584096
TI  - Hookah use among New Jersey youth: associations and changes over time.
AB  - OBJECTIVES: To assess hookah use among youth for prevalence, associations, and
      changes over time. METHODS: Data from the 2008 and 2010 New Jersey Youth Tobacco
      Survey were analyzed to examine hookah smoking by gender, race/ethnicity, and
      grade level. RESULTS: Prevalence  of hookah use increased significantly among
      black and Hispanic students. Frequency of use was generally occasional. In
      multivariate models, Asian race; Hispanic ethnicity; and concurrent use of
      cigarettes, cigars, and bidis predicted current hookah smoking. CONCLUSIONS:
      Prevalence of  hookah use is rising among New Jersey's youth, particularly among
      minority populations, representing a growing public health concern.

PMID- 22584097
TI  - Perceived influences on diet among urban, low-income African Americans.
AB  - OBJECTIVES: To understand perceived influences on consumption of fruits,
      vegetables, and fast foods for urban, low-income African Americans. METHODS: Semi
      structured interviews with 33 African American adults from Philadelphia,
      Pennsylvania, using continuous, iterative,  thematic analysis. RESULTS:
      Influences on dietary behaviors that emerged included economic considerations;
      food characteristics; health concerns and health effects; participants' personal
      influences; social and cultural influences; neighborhood, home, and work
      environments; and broader  contextual influences. There were important
      differences by age group and gender. CONCLUSION: Strategies to improve dietary
      patterns in urban, low-income, African-American communities might make use of
      overall and age- and gender-specific perspectives from within the community we
      report.

PMID- 22584098
TI  - Breast cancer screening practices among Asian Americans and Pacific Islanders.
AB  - OBJECTIVE: To compare the breast cancer screening practices and related factors
      between Asian Americans and Pacific Islanders (PIs) and non-Hispanic whites.
      METHODS: Using 2008 Behavioral Risk Factor Surveillance System data, reported
      mammogram usage among women aged 40+  were compared. Covariates included
      demographics, risk behaviors, health perception, care access, and general health
      practice behavior. RESULTS: PIs had higher rates of screening mammogram usage
      than did Asian Americans. Most covariates had different levels of influence on
      mammogram  screening for the 2 groups, with a few in opposite directions.
      CONCLUSION: Understanding the magnitude and predictors of these disparities for
      racial/ethnic groups can help inform targeted interventions.

PMID- 22584099
TI  - Free-standing and single-crystalline Fe(1-x)Mn(x)Si nanowires with room
      temperature ferromagnetism and excellent magnetic response.
AB  - High-aspect-ratio Fe(1-x)Mn(x)Si nanowires with room-temperature ferromagnetism
      were synthesized by a chemical vapor deposition (CVD) method in one step. This is
      the first report of ternary silicide nanowires using magnetic Mn ions to
      partially replace metal sites in the host matrix. Here we report the excellent
      magnetic characteristics of Fe(1-x)Mn(x)Si nanowires, which exhibit strong
      ferromagnetism at room temperature and high magnetoresistance (MR) variation. As
      synthesized Fe(1-x)Mn(x)Si nanowires show a hyperbranched morphology and a spin
      disorder behavior. The strong spin interaction in Fe(1-x)Mn(x)Si nanowires,
      induced by the substitution of Fe sublattices for magnetic Mn ions, was revealed
      in the hysteresis loops. The magnetization versus magnetic field (M-H) curves of
      Fe(1-x)Mn(x)Si nanowires are much less sensitive to the temperature variation
      from 10 to 300 K than those of FeSi nanowires. Remarkably, the excellent MR
      performance, -41.6% at 25 K with a magnetic field of 9 T, was demonstrated in an
      individual Fe(0.88)Mn(0.12)Si nanowire.

PMID- 22584100
TI  - Trends in drug-resistant tuberculosis in a gold-mining workforce in South Africa,
      2002-2008.
AB  - SETTING AND OBJECTIVE: To describe trends in drug-resistant tuberculosis (TB) in
      two gold-mining workforces, South Africa, 2002-2008. DESIGN: TB programme data
      analysis. RESULTS: TB case notification rates decreased between 2002 and 2008
      from 4006 to 3018 per 100,000 and from 3192 to 2468/100,000 for Companies A and
      B, respectively. Human immunodeficiency virus (HIV) prevalence exceeded 80% in TB
      episodes with known status. The proportion of TB episodes with multidrug
      resistant TB (MDR-TB) increased from 6/129 (4.7%) to 17/85 (20.0%) among
      previously treated cases, and from 4/38 (10.4%) to 7/28 (25.0%) in Companies A
      and B, respectively (tests for trend, Company A, P < 0.001; Company B, P =
      0.304). Case notifications of MDR-TB increased during 2002-2008 from 39.8 to
      122.9/100,000/year in Company A and from 7.8 to 96.8/100,000/year in Company B.
      Coverage of second-line drug susceptibility testing (DST) among MDR-TB episodes
      was low. Previous treatment exposure was a strong risk factor for MDR-TB
      (prevalence ratio 8.78, 95%CI 5.94-12.97 in previously treated vs. untreated
      individuals). CONCLUSION: Despite decreasing TB notifications overall, MDR-TB
      notifications and proportions of episodes with MDR-TB increased in the larger
      company. Cure must be ensured in first episodes to prevent acquired resistance.
      Improved coverage of culture, DST and HIV testing is required to allow treatment
      to be optimised.

PMID- 22584101
TI  - Skin and soft tissue concentrations of tedizolid (formerly torezolid), a novel
      oxazolidinone, following a single oral dose in healthy volunteers.
AB  - Plasma concentrations of antimicrobial drugs have long been used to correlate
      exposure with effect, yet one cannot always assume that unbound plasma and tissue
      concentrations are similar. Knowledge about unbound tissue concentrations is
      important in the development of antimicrobial drugs, since most infections are
      localised in tissues. Therefore, a clinical microdialysis study was conducted to
      evaluate the distribution of tedizolid (TR-700), the active moiety of the
      antimicrobial prodrug tedizolid phosphate (TR-701), into interstitial fluid (ISF)
      of subcutaneous adipose and skeletal muscle tissues following a single oral 600
      mg dose of tedizolid phosphate in fasting conditions. Twelve healthy adult
      subjects were enrolled. Two microdialysis probes were implanted into the thigh of
      each subject, one into the vastus medialis muscle and one into subcutaneous
      adipose tissue. Probes were calibrated using retrodialysis. Dialysate samples
      were collected every 20 min for 12h following a single oral dose of 600 mg
      tedizolid phosphate, and blood samples were drawn over 24h. Unbound tedizolid
      levels in plasma were similar to those in muscle and adipose tissue. The ratios
      of unbound (free) AUC in tissues over unbound AUC in plasma
      (fAUC(tissue)/fAUC(plasma)) were 1.1 +/- 0.2 and 1.2 +/- 0.2 for adipose and
      muscle tissue, respectively. The median half-life was 8.1, 9.2 and 9.6h for
      plasma, adipose tissue and muscle tissue, respectively. Mean protein binding was
      87.2 +/- 1.8%. The study drug was very well tolerated. The results of this study
      show that tedizolid distributes well into ISF of adipose and muscle tissues.
      Unbound levels of tedizolid in plasma, adipose tissue and muscle tissue were well
      correlated. Free plasma levels are indicative of unbound levels in the ISF of
      muscle and adipose tissues.

PMID- 22584102
TI  - Fish oil and vascular endothelial protection: bench to bedside.
AB  - Fish oil is recommended for the management of hypertriglyceridemia and to prevent
      secondary cardiovascular disorders. Fish oil is a major source of omega-3
      polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA). Clinical studies suggest that fish oil not only
      prevents the incidence of detrimental cardiovascular events, but also lowers the
      cardiovascular mortality rate. In addition to a classic lipid-lowering action,
      omega-3-PUFAs in fish oil could regulate blood pressure and enhance vascular
      integrity and compliance. Additionally, omega-3-PUFAs have the ability to protect
      vascular endothelial cells by decreasing oxidative stress, halting
      atherosclerotic events, and preventing vascular inflammatory and adhesion
      cascades. Intriguingly, recent studies have demonstrated that omega-3-PUFAs
      improve the function of vascular endothelium by enhancing the generation and
      bioavailability of endothelium-derived relaxing factor (nitric oxide) through
      upregulation and activation of endothelial nitric oxide synthase (eNOS). This
      certainly opens up a new area of research identifying potential mechanisms
      influencing fish oil-mediated functional regulatory action on vascular
      endothelium. We address in this review the potential of fish oil to prevent
      vascular endothelial dysfunction and associated cardiovascular disorders.
      Moreover, the mechanisms pertaining to fish oil-mediated eNOS activation and
      nitric oxide generation in improving endothelial function are delineated. We
      finally suggest the importance of further studies to determine the dose
      adjustment of fish oil with an optimal ratio of EPA and DHA for achieving
      consistent cardiovascular protection.

PMID- 22584103
TI  - Generation of second messengers in Plasmodium.
AB  - Signalling in malaria parasites is a field of growing interest as its components
      may prove to be valuable drug targets, especially when one considers the burden
      of a disease that is responsible for up to 500 million infections annually. The
      scope of this review is to discuss external stimuli in the parasite life cycle
      and the upstream machinery responsible for translating them into intracellular
      responses, focussing particularly on the calcium signalling pathway.

PMID- 22584104
TI  - Calcium dependent protein kinase 1 and calcium fluxes in the malaria parasite.
AB  - Calcium dependent protein kinases (CDPKs) are found only in plants and alveolates
      and are distinguished from other kinases by an activation domain that binds
      calcium directly. Plants contain families of these kinases and their functions
      are modulated by post translational modifications as well as calcium activation.
      Apicomplexan parasites also contain CDPK families and this review is focused on
      CDPK1 in Plasmodium spp. This enzyme has been implicated in parasite motility and
      host cell invasion and at least two substrates associated with the actomyosin
      motor complex have been identified. By analogy with the plant CDPKs we propose
      that its activity is modulated both by post translational modifications and by
      its subcellular location in a compartment within the parasite's pellicle, which
      may regulate the calcium concentration required for activation.

PMID- 22584105
TI  - Characterization of vascular endothelial progenitor cells from chicken bone
      marrow.
AB  - BACKGROUND: Endothelial progenitor cells (EPC) are a type of stem cell used in
      the treatment of atherosclerosis, vascular injury and regeneration. At present,
      most of the EPCs studied are from human and mouse, whereas the study of poultry
      derived EPCs has rarely been reported. In the present study, chicken bone marrow
      derived EPCs were isolated and studied at the cellular level using
      immunofluorescence and RT-PCR. RESULTS: We found that the majority of chicken
      EPCs were spindle shaped. The growth-curves of chicken EPCs at passages (P) 1, -5
      and -9 were typically "S"-shaped. The viability of chicken EPCs, before and after
      cryopreservation was 92.2% and 81.1%, respectively. Thus, cryopreservation had no
      obvious effects on the viability of chicken EPCs. Dil-ac-LDL and FITC-UAE-1
      uptake assays and immunofluorescent detection of the cell surface markers CD34,
      CD133, VEGFR-2 confirmed that the cells obtained in vitro were EPCs. Observation
      of endothelial-specific Weibel-Palade bodies using transmission electron
      microscopy further confirmed that the cells were of endothelial lineage. In
      addition, chicken EPCs differentiated into endothelial cells and smooth muscle
      cells upon induction with VEGF and PDGF-BB, respectively, suggesting that the
      chicken EPCs retained multipotency in vitro. CONCLUSIONS: These results suggest
      that chicken EPCs not only have strong self-renewal capacity, but also the
      potential to differentiate into endothelial and smooth muscle cells. This
      research provides theoretical basis and experimental evidence for potential
      therapeutic application of endothelial progenitor cells in the treatment of
      atherosclerosis, vascular injury and diabetic complications.

PMID- 22584106
TI  - Stabilization of Cr(VI) from fine ferrochrome dust using exfoliated vermiculite.
AB  - This study proved that vermiculite, a natural occurring mineral, can effectively
      remove and stabilize Cr(VI) from fine ferrochrome dust leachate. Batch adsorption
      studies were carried out to determine the effect of pH, contact time and
      adsorbent dose on the removal of Cr(VI). The process was found to be highly pH
      dependent. The optimum conditions for the Cr(VI) removal are at a pH of 1.5,
      contact time of 2h and adsorbent dose of 10gL(-1). The stability of the Cr(VI)
      loaded vermiculite remained unchanged after 12 months, when the vermiculite was
      evaluated with the ASTM and TCLP Cr(VI) leach methods. However, Cr(VI) desorption
      did take place when the Acid Rain Test was used. The adsorption kinetic data fits
      the pseudo-second order model, while the equilibrium data of Cr(VI) adsorption
      onto vermiculite are best described by the Langmuir isotherm. The presence of
      hydrobiotite and biotite in the industrial vermiculite slightly decreased the
      degree of adsorption of Cr(VI).

PMID- 22584107
TI  - Myocardial motion and deformation: What does it tell us and how does it relate to
      function?
AB  - The assessment of cardiac pump function and the potential of local myocardium to
      contribute to the overall performance are of great importance in many
      cardiovascular abnormalities. Assessing intrinsic cardiac function requires
      obtaining information on the true contractility of the heart muscle, assessed
      locally but interpreted in the context of its contribution to the global ejection
      performance and potential to adapt to changing circumstances. Contemporary
      imaging techniques offer the possibility of noninvasive quantification of
      myocardial deformation. These new clinical tools are attractive to use for the
      assessment of ventricular function. However, it is of great importance to
      understand cardiac mechanics - a complex interplay between the tissue
      structure/shape, force development, and interaction with the
      environment/neighbors - to interpret alterations in deformation and to extract
      clinically relevant conclusions. The combination of insight into the measurement
      techniques and their limitations, together with knowledge of myocardial mechanics
      and physiology, opens new perspectives to improve the assessment and management
      of fetal, pediatric, and adult patients.

PMID- 22584108
TI  - Recurrent long-lasting tethering reduces BDNF protein levels in the dorsal
      hippocampus and frontal cortex in pigs.
AB  - Brain-derived neurotrophic factor (BDNF) signaling has been implicated in the
      onset of depression and in antidepressant efficacy, although the exact role of
      this neurotrophin in the pathophysiology of depression remains to be elucidated.
      Also, the interaction between chronic stress, which may precede depression,
      corticosteroids and BDNF is not fully understood. The present study aimed at
      investigating whether long-lasting, recurrent tethering of sows during a period
      of 1.5 or 4.5 years leads to enduring effects on measures that may be indicative
      of chronic stress, compared with animals kept in a group housing system ('loose'
      sows). Immediately after slaughter, the frontal cortex, dorsal and ventral
      hippocampus were dissected and protein levels of BDNF and its receptors were
      analyzed and compared with plasma cortisol levels and adrenal weights. Results
      indicate that tethering stress reduced BDNF protein levels in the dorsal
      hippocampus and the frontal cortex, but not in the ventral hippocampus. In
      addition, levels of TrkB, the high affinity receptor for BDNF, were increased in
      the dorsal hippocampus. Plasma cortisol levels and adrenal weight were increased
      after tethering. These stress effects on BDNF levels were more pronounced after
      4.5 years of recurrent tethering and negatively correlated in particular in the
      frontal cortex with cortisol levels and adrenal weight. This suggests that the
      stress effect of tethered housing on neurotrophin levels may be mediated via
      cortisol. Taken together, these data indicate that recurrent tethering stress in
      sows over 4.5 years results in a loss of neurotrophic support by BDNF, mediated
      by an overactive neuroendocrine system.

PMID- 22584109
TI  - Use of PCR for detection of faecal HAV as a screening tool in an outbreak of
      hepatitis A in daycare centres.
AB  - Using polymerase chain reaction (PCR) to detect faecal hepatitis A virus (HAV)
      can be a useful tool for investigating HAV outbreaks, especially in low-endemic
      countries. We describe the use of faecal HAV PCR as a non-invasive tool for
      screening. Two Dutch children visiting different daycare centres were diagnosed
      with hepatitis A in 2011. A systematic contact investigation was started in the
      daycare centres and relevant contacts were screened. The faecal HAV PCR test was
      used to screen the children. The employees were screened with a serum IgM. The
      faecal HAV PCR test proved to be an appropriate tool for screening. The screening
      of a total of 135 children and employees in the daycare centres resulted in
      evidence of eight asymptomatic infections and transmission to three related
      daycare centres. Control measures were taken including immunization. Compared to
      an epidemiological investigation without screening, 144 extra contacts were
      vaccinated based on the screening results. This most likely led to improved
      prevention of expansion of the outbreak.

PMID- 22584110
TI  - Primary extranodal non-Hodgkin's lymphoma of the vagina: a case report and a
      review of the literature.
AB  - Primary lymphoma of the female genital tract is very rare. We report the case of
      a 36-year-old woman who was referred to our hospital because of an indeterminate
      Pap smear test. The colposcopy showed a thickening of the posterior vaginal wall
      and various irregular ulcerated nodular lesions. Histological examination,
      immunohistochemistry and the staging procedures were conclusive of diffuse large
      B-cell lymphoma of the vagina, stage IEA. Complete remission was achieved after 6
      cycles of immunopolychemotherapy (rituximab, cyclophosphamide, doxorubicin,
      vincristine and prednisone). No relapse has occurred during a follow-up of 71
      months. Moreover, we reviewed the 62 previously reported cases of primary
      extranodal non-Hodgkin's lymphoma of the vagina, focusing on clinicopathological
      and therapeutic aspects, to better characterize this unusual disease.

PMID- 22584111
TI  - Bioaerosols in residential micro-environments in low income countries: a case
      study from Pakistan.
AB  - Our knowledge of the concentrations of bioaerosols in residential micro
      environments in low income countries is scanty. The present investigation was
      conducted to assess the culturable concentration and size distribution of
      bacteria, gram negative bacteria and fungi in two rural and an urban site in
      Pakistan. The highest indoor culturable bacteria concentration was found at Rural
      Site II (14,650 CFU/m3) while the outdoor maximum occurred at the urban site
      (16,416 CFU/m3). With reference to fungi, both indoor and outdoor concentrations
      were considerably higher at Rural Site I than the other sites. The size
      distribution of culturable bacteria at all sites showed greater variability than
      that of culturable fungi. At all sites more than the half (55-93%) of the
      culturable bacterial and fungal counts were observed in the respirable fraction
      (<4.7 MUm) and so had the potential to penetrate into lower respiratory system.

PMID- 22584112
TI  - Contrasting levels of heavy metals in the feathers of urban pigeons from close
      habitats suggest limited movements at a restricted scale.
AB  - Despite restrictions in emissions, heavy metals may remain a major environmental
      issue due to their numerous sources and their persistence. Here, we assessed
      current levels of 4 metals (Copper, Cadmium, Lead, Zinc) in the feathers of 91
      feral pigeons (Columba livia) from 7 sites in the urbanized region of Paris.
      Elements were detected in all pigeons, indicating that metals persist in
      urbanized areas. The ratio between metal concentrations in the feathers vs. in
      the environment calculated using data from other studies was 2-90 times higher
      for cadmium than for other metals, underlying its ecological importance.
      Concentrations in the feathers depended on locality, suggesting that pigeons
      remain in local habitats at this restricted scale, as expected from previous
      observations. Overall, our study suggests that urban feral pigeons may represent
      a good model system for metal biomonitoring.

PMID- 22584113
TI  - Identification Of Small Molecule TRABID Deubiquitinase Inhibitors By Computation
      Based Virtual Screen.
AB  - BACKGROUND: Wnt/beta-catenin-mediated gene transcription plays important roles in
      a wide range of biological and pathophysiological processes including
      tumorigenesis where beta-catenin-mediated transcription activity frequently
      elevates. TRABID, a deubiquitinase, was shown to have a positive Wnt/beta-catenin
      mediated gene transcription and hence holds a promise as a putative anti-cancer
      target. RESULTS: In this study, we used a combination of structure based virtual
      screening and an in vitro deubiquitinase (DUB) assay to identify several small
      molecules that inhibit TRABID DUB activity. However, these inhibitors failed to
      show inhibitory effects on beta-catenin-mediated gene transcription. In addition,
      expression of TRABID shRNAs, wildtype TRABID, or the DUB activity-deficient
      mutant showed little effects on beta-catenin-mediated gene transcription.
      CONCLUSIONS: TRABID may not be a critical component in canonical Wnt/beta-catenin
      signal transduction or that a minute amount of this protein is sufficient for its
      role in regulating Wnt activity.

PMID- 22584114
TI  - Using the NIHR Comprehensive Clinical Research Network for infectious diseases
      and microbiology research.

PMID- 22584115
TI  - Diaphragmatic rupture: Is management with biological mesh feasible?
AB  - INTRODUCTION: Blunt diaphragmatic rupture is a rare event that may occur after
      traumatic injury. Due to its rarity and difficulty in diagnosing, delayed
      detection of diaphragmatic injuries can occur. Management involves repair of the
      diaphragmatic defect via trans-thoracic and/or trans-abdominal approaches. Most
      small repairs may be repaired primarily, larger defects have been historically
      repaired with mesh. PRESENTATION OF CASE: We report a case series of five
      patients with diaphragmatic injuries all repaired with biologic mesh via both
      trans-thoracic and trans-abdominal approaches. DISCUSSION: Delayed presentation
      is the single most important contributor to increased morbidity and mortality in
      patients with blunt diaphragmatic rupture. Our case series corroborates other
      findings that patients with blunt diaphragmatic ruptures are at high risk for
      infection and thus may be repaired with use of biologic mesh versus the
      traditional use of synthetic mesh. This can be done without high rates of
      recurrence or complications from use of biologic mesh. CONCLUSION: In our series,
      we successfully repaired 5 diaphragmatic defects with the use of biologic mesh.
      With follow-up as much as 4 years out, none of our patients have had an
      infectious complication with the use biologic mesh and there is no evidence of
      recurrence or eventration. The use of biologic mesh is an acceptable alternative
      to the traditional use of synthetic mesh in the repair of both acute and chronic
      diaphragmatic defects.

PMID- 22584116
TI  - Body mass index influences the response to infliximab in ankylosing spondylitis.
AB  - INTRODUCTION: The excess of adipose tissue in obese individuals may have
      immunomodulating properties and pharmacokinetic consequences. The aim of this
      study was to determine whether body mass index (BMI) affects response to
      infliximab (IFX) in ankylosing spondylitis (AS) patients. METHODS: In 155
      patients retrospectively included with active AS, the BMI was calculated before
      initiation of IFX treatment (5 mg/kg intravenously). After 6 months of treatment,
      changes from baseline in BASDAI, Visual Analogue Scale (VAS) pain, C-reactive
      protein (CRP) level, and total dose of nonsteroidal antiinflammatory drug (NSAID)
      were dichotomized with a threshold corresponding to a decrease of 50% of initial
      level of the measure, into binary variables assessing response to IFX (BASDAI50,
      VAS50, CRP50, NSAID50). Whether the BMI was predictive of the response to IFX
      therapy according to these definitions was assessed with logistic regression.
      RESULTS: Multivariate analysis found that a higher BMI was associated with a
      lower response for BASDAI50 (P = 0.0003; OR, 0.87; 95% CI (0.81 to 0.94)), VAS50
      (P < 0.0001; OR, 0.87; 95% CI (0.80 to 0.93)); CRP50 (P = 0.0279; OR, 0.93; 95%
      CI (0.88 to 0.99)), and NSAID50 (P = 0.0077; OR, 0.91; 95% CI (0.85 to 0.97)),
      criteria. According to the three WHO BMI categories, similar results were found
      for BASDAI50 (77.6%, 48.9%, and 26.5%; P < 0.0001), VAS50 (72.6%, 40.4%, and
      16.7%; P < 0.0001); CRP50 (87.5%, 65.7%, and 38.5%; P = 0.0001), and NSAID50
      (63.2%, 51.5%, and 34.6%; P = 0.06). CONCLUSIONS: This study provides the first
      evidence that a high BMI negatively influences the response to IFX in AS. Further
      prospective studies, including assessment of the fat mass, pharmacokinetics, and
      adipokines dosages are mandatory to elucidate the role of obesity in AS IFX
      response.

PMID- 22584117
TI  - Efficacy versus effectiveness: a direct comparison of the outcome of treatment
      for mild to moderate depression in randomized controlled trials and daily
      practice.
AB  - BACKGROUND: Results from randomized controlled trials (RCTs) are considered to
      give the most reliable information on treatment outcome (efficacy). Yet, the
      generalizability of efficacy results to daily practice (effectiveness) might be
      diminished by the design of RCTs. The STAR*D trial approached daily practice as
      much as possible, but still has some properties of an RCT. In this study, we
      compare results from treatment of major depressive disorder (MDD) in routine
      clinical practice to those of RCTs and STAR*D. METHODS: Effectiveness in routine
      clinical practice was compared with efficacy results from 15 meta-analyses on
      antidepressant, psychotherapeutic and combination treatment and results from
      STAR*D. Data on daily practice patients and treatments were derived from a
      routine outcome monitoring (ROM) system. Treatment outcome was defined as
      proportion of remitters (MADRS <=10) and within-group effect size. RESULTS: From
      ROM, 598 patients suffering from a MDD episode according to the MINI-plus were
      included. Remission percentages were lower in routine practice than in meta
      analyses for all treatment modalities (32 vs.40-74%). Differences were less
      explicit for antidepressants (21 vs. 34-47%) than for individual psychotherapy
      (27 vs. 34-58%; effect size 0.85 vs. 1.71) and combination therapy (21 vs. 45
      63%), since only 60% of the meta-analyses for antidepressants showed significant
      differences with ROM, while for psychotherapy and combination treatment almost
      all meta-analyses showed significant differences. No differences in effectiveness
      were found between routine practice and STAR*D (antidepressants 27 vs. 28%;
      individual psychotherapy 27 vs. 25%; combination treatment 21 vs. 23%,
      respectively). CONCLUSIONS: Effectiveness of treatment for mild-to-moderate MDD
      in daily practice is similar to STAR*D and significantly lower than efficacy
      results from RCTs.

PMID- 22584118
TI  - Two motifs with different function regulate the anterograde transport of the
      adiponectin receptor 1.
AB  - The anterograde trafficking of GPCR has been described as a tightly controlled
      process involving specific amino acid sequences that mediate the receptor
      transport. In this study, we investigated whether the cell surface delivery of
      the adiponectin receptor 1, a newly identified class of heptahelix receptors
      different from G protein-coupled receptors, is regulated. Sequential N-terminal
      deletion revealed that the export of the AdipoR1 from the endoplasmic reticulum
      (ER) is controlled by distinct parts of the receptor N-terminus. Strong evidence
      is provided that the ER exit is mediated by two specific sequences, a
      F(X)(3)F(X)(3)F and a D(X)(3)LL motif. Disruption of these motifs led to a
      substantial accumulation of the AdipoR1 in the ER. Mutation of similar motifs in
      the AdipoR1 C-terminus did not result in aberrant receptor localization,
      suggesting that these motifs are sequence and position specific to the AdipoR1 N
      terminus. Further analysis of the regulation mechanism identified an interaction
      with the chaperone BiP and additionally, strong evidence is provided that both
      motifs exert different biological function in the AdipoR1 ER export. In
      conclusion, our data demonstrate that the receptor transport shares similar ER
      exit motifs although AdipoR are structurally different from GPCR. However, since
      even two specific sequences are identified, the anterograde trafficking of the
      AdipoR1 seems to be regulated in a more complex manner.

PMID- 22584119
TI  - Perifosine sensitizes UVB-induced apoptosis in skin cells: new implication of
      skin cancer prevention?
AB  - We demonstrate here that a relative low dose of perifosine significantly enhanced
      UVB-induced apoptosis in skin cells (keratinocytes and fibroblasts), associated
      with a significant increase of reactive oxygen species (ROS) and ceramide
      production as well as multiple perturbations of diverse cell signaling pathways,
      shifting to a significant pro-apoptosis outcomes. Perifosine inhibited UVB
      induced pro-survival Akt/mammalian target of rapamycin (mTOR) and ERK activation,
      while facilitating pro-apoptotic AMP-activated protein kinas (AMPK), c-Jun-NH(2)
      kinase (JNK), and p53 activation; these signaling changes together promoted a
      striking increase in skin cell apoptosis and a significantly reduced amount of
      DNA damages. Our results suggest that perifosine may represent a novel skin
      cancer prevention strategy.

PMID- 22584120
TI  - Haemoparasites of free-roaming dogs associated with several remote Aboriginal
      communities in Australia.
AB  - BACKGROUND: Tick-borne haemoparasites Babesia vogeli and Anaplasma platys are
      common among the free-roaming canine populations associated with Aboriginal
      communities in Australia, whilst the prevalence of haemoplasmas, which are also
      suspected to be tick-borne, remained unexplored. The aim of this study was to
      determine the prevalence of haemoplasma infection in these populations, and to
      identify any correlation with other haemoparasites. Blood was collected from 39
      dogs associated with four Aboriginal communities and screened for infection using
      PCR and serology. DNA was purified and PCR analyses for piroplasms,
      Anaplasmataceae family bacteria and haemoplasmas performed. Serum was analysed
      using a commercial haemoparasite ELISA. Prevalence of infection was compared
      between communities. RESULTS: Seventeen dogs (44%) were infected (PCR positive)
      with Mycoplasma haemocanis, eight (21%) with 'Candidatus Mycoplasma
      haematoparvum', 20 (51%) with A. platys, and 17 (44%) with B. vogeli. Two dogs
      were infected with a novel haemoplasma as determined by DNA amplification and
      sequencing. Two dogs (5%) were serologically positive for Dirofilaria immitis
      antigens, one (3%) was positive for Ehrlichia canis antibodies and nine
      (24nbsp;%) were positive for A. platys antibodies. Co-infections were frequent.
      Haemoplasma prevalence was highest (73%, 16/22) in Central Australia and lowest
      (22%, 2/9) in Western Australia (p = 0.017). In contrast, B. vogeli prevalence
      was low in Central Australia (18%, 4/22) but higher (78%, 7/9) in Western
      Australia (p = 0.003). CONCLUSIONS: This is the first time haemoplasma
      infections, including a novel species, have been molecularly documented in
      Australian dogs. The wide regional variation in prevalence of some of the
      haemoparasite infections detected in this study warrants further investigation.

PMID- 22584121
TI  - Oral sensorimotor integration in adults who stutter.
AB  - OBJECTIVE: To investigate the relationship between tendon vibration sensitivity
      and oral motor control in adults who stutter (AWS). PATIENTS AND METHODS: Ten
      controls and 10 AWS first made jaw-opening movements from a closed-mouth position
      to an 18-mm target. Then, masseter tendon vibration was applied during jaw
      opening in a separate condition to test whether accuracy and/or variability is
      related to movement undershoot. RESULTS: AWS made less accurate and more variable
      jaw movements than controls without visual feedback. Among the normally fluent
      adult participants, higher accuracy and lower variability were significantly
      related to masseter vibration undershoot, but significant correlations were not
      observed for AWS. CONCLUSION: These results suggest that increased tendon
      vibration sensitivity may be related to more refined oral motor control. Subtle
      sensorimotor limitations could be present in stuttering that render speech more
      susceptible to breakdowns.

PMID- 22584122
TI  - SAR131675, a potent and selective VEGFR-3-TK inhibitor with antilymphangiogenic,
      antitumoral, and antimetastatic activities.
AB  - SAR131675 is a potent and selective VEGFR-3 inhibitor. It inhibited VEGFR-3
      tyrosine kinase activity and VEGFR-3 autophosphorylation in HEK cells with IC(50)
      values of 20 and 45 nmol/L, respectively. SAR131675 dose dependently inhibited
      the proliferation of primary human lymphatic cells, induced by the VEGFR-3
      ligands VEGFC and VEGFD, with an IC(50) of about 20 nmol/L. SAR131675 was found
      to be highly selective for VEGFR-3 versus 107 receptors, enzymes, ion channels,
      and 65 kinases. However, it was moderately active on VEGFR-2 with a VEGFR-3/VEGFR
      2 ratio of about 10. SAR131675 had no antiproliferative activity on a panel of 30
      tumors and primary cells, further showing its high specificity and indicating
      that SAR131675 is not a cytotoxic or cytostatic agent. SAR131675 was very well
      tolerated in mice and showed a potent antitumoral effect in several orthotopic
      and syngenic models, including mammary 4T1 carcinoma and RIP1.Tag2 tumors.
      Interestingly, it significantly reduced lymph node invasion and lung metastasis,
      showing its antilymphangiogenic activity in vivo. Moreover, treatment of mice
      before resection of 4T1 primary tumors was sufficient to prevent metastasis.
      Tumor-associated macrophages (TAM) play an important role in tumor growth and
      metastasis. The expression of VEGFR-3 on TAMs has been recently described. F4/80
      immunostaining clearly showed that SAR131675 significantly reduced TAM
      infiltration and aggregation in 4T1 tumors. Taken together, SAR131675 is the
      first highly specific VEGFR-3-TK inhibitor described to date, displaying
      significant antitumoral and antimetastatic activities in vivo through inhibition
      of lymphangiogenesis and TAM invasion.

PMID- 22584123
TI  - CTLA-4 blockade expands infiltrating T cells and inhibits cancer cell
      repopulation during the intervals of chemotherapy in murine mesothelioma.
AB  - Cancer immunotherapy has shown promising results when combined with chemotherapy.
      Blocking CTLA-4 signaling by monoclonal antibody between cycles of chemotherapy
      may inhibit cancer cell repopulation and enhance the antitumoral immune reaction,
      thus improve the efficacy of chemotherapy in mesothelioma. The impact of CTLA-4
      blockade on the early stage of tumor development was evaluated in a subcutaneous
      murine mesothelioma model. CTLA-4 blocking antibody was administered following
      each cycle of chemotherapy, and monotherapy was included as controls. Antitumor
      effect was evaluated by tumor growth delay and survival of the animals. Tumor
      cell repopulation was quantified by bromodeoxyuridine incorporation and Ki67 by
      immunohistochemistry and/or flow cytometry. In vitro cell killing was determined
      by classic chromium-released assay, and reverse transcription PCR (RT-PCR) was
      carried out to determine the gene expression of associated cytokines. Anti-CTLA-4
      monoclonal antibody was able to inhibit tumor growth at early stage of tumor
      development. Antitumor effect was achieved by administration of CTLA-4 blockade
      between cycles of chemotherapy. Tumor cell repopulation during the intervals of
      cisplatin was inhibited by CTLA-4 blockade. Anti-CTLA-4 therapy gave rise to an
      increased number of CD4 and CD8 T cells infiltrating the tumor. RT-PCR showed
      that the gene expression of interleukin IL-2, IFN-gamma, granzyme B, and perforin
      increased in the tumor milieu. Blockade of CTLA-4 signaling showed effective
      anticancer effect, correlating with inhibiting cancer cell repopulation between
      cycles of chemotherapy and upregulating tumor-infiltrating T lymphocytes,
      cytokines, and cytolytic enzymes in a murine mesothelioma model.

PMID- 22584124
TI  - Impact of patient and program factors on default during treatment of multidrug
      resistant tuberculosis.
AB  - SETTING: In the Philippines, programmatic treatment of drug-resistant
      tuberculosis (TB) was initiated by the Tropical Disease Foundation in 1999 and
      transitioned to the National TB Program in 2006. OBJECTIVE: To determine patient
      and socio-demographic characteristics associated with default, and the impact of
      patient support measures on default. DESIGN: Retrospective cohort analysis of 583
      MDR-TB patients treated from 1999 to 2006. RESULTS: A total of 88 (15%) patients
      defaulted from treatment. The median follow-up time for patients who defaulted
      was 289 days (range 1-846). In multivariate analysis adjusted for age, sex and
      previous TB treatment, receiving a greater number of treatment drugs (>= 5 vs. 2
      3 drugs, HR 7.2, 95%CI 3.3-16.0, P < 0.001) was significantly associated with an
      increased risk of default, while decentralization reduced the risk of default (HR
      0.3, 95%CI 0.2-0.7, P < 0.001). CONCLUSION: Improving access to treatment for MDR
      TB through decentralization of care to centers near the patient's residence
      reduced the risk of default. Further research is needed to evaluate the
      feasibility, impact and cost-effectiveness of decentralized care models for MDR
      TB treatment.

PMID- 22584125
TI  - Spectroscopic investigation on the interaction of 9-aminoacridine with certain
      dyes.
AB  - The fluorescence quenching of 9-Aminoacridine (9-AA) by various dyes were probed
      in aqueous medium using steady state and time resolved fluorescence spectroscopic
      techniques. From these techniques, we had rationalized the interaction of 9-AA
      with various dyes via ground state complex formation. The binding constant (K)
      and number of binding sites (n) were calculated from the relevant fluorescence
      quenching data. The fluorescence emission of 9-Aminoacridine was quenched by the
      dyes through static quenching followed by the mechanism of energy transfer. The
      static quenching mechanism was confirmed by lifetime measurements. The
      thermodynamic parameters such as free energy change (DeltaG), enthalpy change
      (DeltaH) and entropy change (DeltaS), were calculated by thermodynamic equations.
      The results showed that Van der Waals interaction or hydrogen bond formation
      played a major role in the binding of 9-AA with these dyes.

PMID- 22584126
TI  - Studies on interaction between an imidazole derivative and bovine serum by
      spectral methods.
AB  - The interaction between a trifluoromethyl substituted imidazole derivative 2-(4
      (trifluoromethyl)phenyl)-1-phenyl-1H-imidazo[4,5-f] [1,10] phenanthroline
      (tfmppip) and bovine serum albumin (BSA) was investigated by solution spectral
      studies. The observed experimental result shows that the imidazole derivative has
      strong ability to quench the fluorescence of BSA by forming complex which is
      stabilized by electrostatic interactions. The effective quenching constants
      (k(sv)) were 2.79 * 10(4), 2.51 * 10(4), and 2.32 * 10(4) at 301, 310 and 318K
      respectively. The Stern-Volmer quenching constant (K(sv)), binding site number
      (n), apparent binding constant (K(A)) and corresponding thermodynamic parameters
      (DeltaG, DeltaH and DeltaS) were calculated. The distance between the donor (BSA)
      and acceptor (tfmppip) was obtained according to fluorescence resonance energy
      transfer (FRET). Conformational changes of BSA were observed from synchronous
      fluorescence technique. The effect of metal ions such as Cu(2+), Zn(2+), Ca(2+),
      Mg(2+), Ni(2+), Co(2+) and Fe(2+) on the binding constants between the imidazole
      derivative and BSA were also studied.

PMID- 22584127
TI  - Biological and chemical study of fused tri- and tetracyclic indazoles and
      analogues with important antiparasitic activity.
AB  - A series of fused tri- and tetracyclic indazoles and analogues compounds (NID)
      with potential antiparasitic effects were studied using voltamperometric and
      spectroscopic techniques. Nitroanion radicals generated by cyclic voltammetry
      were characterized by electron spin resonance spectroscopy (ESR) and their
      spectral lines were explained and analyzed using simulated spectra. In addition,
      we examined the interaction between radical species generated from nitroindazole
      derivatives and glutathione (GSH). Biological assays such as activity against
      Trypanosoma cruzi and cytotoxicity against macrophages were carried out. Finally,
      spin trapping and molecular modeling studies were also done in order to elucidate
      the potentials action mechanisms involved in the trypanocidal activity.

PMID- 22584128
TI  - The osteogenic response of undifferentiated human adipose-derived stem cells
      under mechanical stimulation.
AB  - The purpose of this study was to investigate the osteogenic response of human
      adipose-derived stem cells (hASCs) under mechanical and/or chemical stimulation.
      hASCs were divided into three groups. In group A, the cells were cultured without
      any stimulation, in group B, the cells were induced with chemical stimulation,
      and in group C, the cells were induced with a combination of chemical stimulation
      and stretch loading. Stretch loading and chemical stimulation were applied using
      a four-point bending apparatus (0.5 Hz, 2,000 uepsilon, 2 h/day) and osteogenic
      differentiation medium, respectively. At the 1st, 2nd, 3rd, 5th and 7th day
      following initiation of stretch loading, we detected alkaline phosphatase
      activity, mRNA expression (RUNX2, ALPL, osteonectin, osteopontin and type I
      collagen) and protein expression (RUNX2 and osteopontin) by colorimetric assay,
      real-time PCR and Western blot methods, respectively. Alkaline phosphatase
      activity, mRNA expression and protein expression all increased in groups B and C
      along with the culture time, but were observed to be downregulated by the 7th day
      in group C (p < 0.05). Compared to group A, most of the above markers were
      significantly higher in groups B and C (p < 0.05). All of the above markers in
      group C were higher than those in group B before the 5th day (p < 0.05), except
      at the 1st day. These results indicated that stretch loading promoted osteogenic
      differentiation of hASCs and that the combination of mechanical and chemical
      stimulation could enhance the osteogenic capability up to the 5th day relative to
      chemical stimulation alone.

PMID- 22584129
TI  - Immuno-epidemiology of chronic bacterial and helminth co-infections: observations
      from the field and evidence from the laboratory.
AB  - Co-infections can alter the host immune responses and modify the intensity and
      dynamics of concurrent parasitic species. The extent of this effect depends on
      the properties of the system and the mechanisms of host-parasite and parasite
      parasite interactions. We examined the immuno-epidemiology of a chronic co
      infection to reveal the immune mediated relationships between two parasites
      colonising independent organs, and the within-host molecular processes
      influencing the dynamics of infection at the host population level. The
      respiratory bacterium, Bordetella bronchiseptica, and the gastrointestinal
      helminth, Graphidium strigosum, were studied in the European rabbit (Oryctolagus
      cuniculus), using long-term field data and a laboratory experiment. We found that
      65% of the rabbit population was co-infected with the two parasites; prevalence
      and intensity of co-infection increased with rabbit age and exhibited a strong
      seasonal pattern with the lowest values recorded during host breeding (from April
      to July) and the highest in the winter months. Laboratory infections showed no
      significant immune-mediated effects of the helminth on bacterial intensity in the
      lower respiratory tract but a higher abundance was observed in the nasal cavity
      during the chronic phase of the infection, compared with single bacterial
      infections. In contrast, B. bronchiseptica enhanced helminth intensity and this
      was consistent throughout the 4-month trial. These patterns were associated with
      changes in the immune profiles between singly and co-infected individuals for
      both parasites. This study confirmed the general observation that co-infections
      alter the host immune responses but also highlighted the often ignored role of
      bacterial infection in helminth dynamics. Additionally, we showed that G.
      strigosum had contrasting effects on B. bronchiseptica colonising different parts
      of the respiratory tract. At the host population level our findings suggest that
      B. bronchiseptica facilitates G. strigosum infection, and re-infection with G.
      strigosum assists in maintaining bacterial infection in the upper respiratory
      tract and thus long-term persistence.

PMID- 22584130
TI  - A Rhipicephalus (Boophilus) microplus cathepsin with dual peptidase and
      antimicrobial activity.
AB  - The cattle tick, Rhipicephalus (Boophilus) microplus, is a haematophagous
      arthropod responsible for considerable losses in the livestock industry.
      Immunological control with vaccines is a promising alternative to replace
      chemical acaricides. Due to their importance in parasite physiology, cysteine
      endopeptidases are potential targets. In a previous study, native Vitellin
      Degrading Cysteine Endopeptidase (VTDCE) was successfully tested as a vaccine
      antigen for bovines against R. microplus. In this work, nucleotide and amino acid
      VTDCE sequences were obtained from cDNA databanks, based on data from Edman
      sequencing and mass spectrometry. Subsequently, cloning and expression,
      purification, immunological and biochemical characterisation of the recombinant
      protein were performed to determine the biological importance of VTDCE. By
      Western blot, polyclonal antibodies produced against recombinant VTDCE recognised
      native VTDCE. Interestingly, molecular analysis showed that the VTDCE sequence
      has similarity to antimicrobial peptides. Indeed, experimental results revealed
      that VTDCE has an antimicrobial activity which is independent of endopeptidase
      activity. We believe that this is the first known study to show that an arthropod
      enzyme has antimicrobial activity.

PMID- 22584131
TI  - Recombinant glycoprotein 63 (Gp63) of Trypanosoma carassii suppresses
      antimicrobial responses of goldfish (Carassius auratus L.) monocytes and
      macrophages.
AB  - We previously reported that proteins secreted by Trypanosoma carassii play a role
      in evasion of fish host immune responses. To further understand how these
      parasites survive in the host, we cloned and expressed T. carassii glycoprotein
      63 (Tcagp63), and generated a rabbit polyclonal antibody to the recombinant
      protein (rTcagp63). Tcagp63 was similar to gp63 of other trypanosomes and grouped
      with Trypanosoma cruzi and Trypanosoma brucei gp63 in phylogenetic analysis. We
      showed that rTcagp63 down-regulated Aeromonas salmonicida and recombinant
      goldfish TNFalpha2-induced production of reactive oxygen and nitrogen
      intermediates. Macrophages treated with rTcagp63 also exhibited significant
      reduction in the expression of inducible nitric oxide synthase (iNOS)-A, TNFalpha
      1 and TNFalpha-2. Recombinant Tcagp63 bound to and was internalised by goldfish
      macrophages. The Tcagp63 may act by altering the signalling events important in
      downstream monocyte/macrophage antimicrobial and other cytokine-induced
      functions. We believe that this is the first report on downregulation of
      antimicrobial responses by trypanosome gp63.

PMID- 22584133
TI  - Analysis of glucose responses to automated insulin suspension with sensor
      augmented pump therapy.
AB  - OBJECTIVE: The advent of sensor-augmented pump therapy with a low-glucose suspend
      (LGS) function (Medtronic Paradigm Veo System), allowing insulin to be
      automatically suspended for up to 2 h when sensor glucose falls below a preset
      threshold, has the potential to reduce the duration of hypoglycemia. In this
      article, we analyzed blood glucose profiles following a full 2-h insulin
      suspension activated by the LGS function, as well as examined different patterns
      of use among patients. RESEARCH DESIGN AND METHODS: Data from a cohort of
      participants using the Veo System for up to 6 months were analyzed to determine
      the time and duration of insulin suspension activated by the LGS function. We
      further evaluated overnight suspend events with no patient response occurring
      prior to 3:00 a.m., which allowed us to determine the pattern of sensor glucose
      values with no patient intervention during and after the period of insulin
      suspension. RESULTS: There were 3,128 LGS events during the 2,493 days evaluated.
      The median duration was 11.2 min, and 36% of events occurred overnight. There
      were 126 full 2-h suspend events that occurred overnight with no patient
      response, occurring before 3:00 a.m. For these events, the mean sensor glucose at
      the end of the 2-h suspend period was 99 +/- 6 mg/dL ([means +/- SE] 5.5 +/- 0.3
      mmol/L). The mean sensor glucose 2 h after insulin delivery resumed was 155 +/-
      10 mg/dL (8.6 +/- 0.6 mmol/L). There were no episodes of severe hypoglycemia or
      diabetic ketoacidosis. CONCLUSIONS: Analyses of sensor glucose patterns following
      insulin suspension activated by LGS suggest that this technology is safe and
      unlikely to be associated with adverse outcomes.

PMID- 22584134
TI  - Effect of intensive versus standard blood pressure control on depression and
      health-related quality of life in type 2 diabetes: the ACCORD trial.
AB  - OBJECTIVE: We tested the hypothesis that intensive (systolic blood pressure [SBP]
      <120 mmHg) rather than standard (SBP 130-139 mmHg) blood pressure (BP) control
      improves health-related quality of life (HRQL) in those with type 2 diabetes.
      RESEARCH DESIGN AND METHODS: Subjects were 1,028 ACCORD (Action to Control
      Cardiovascular Risk in Diabetes) BP trial HRQL substudy participants who
      completed baseline and one or more 12-, 36-, or 48-month HRQL evaluations.
      Multivariable linear regression assessed impact of BP treatment assignment on
      change in HRQL. RESULTS: Over 4.0 years of follow-up, no significant differences
      occurred in five of six HRQL measures. Those assigned to intensive (vs. standard)
      BP control had statistically significant worsening of the Medical Outcomes Study
      36-item short-form health survey (SF36) physical component scores (-0.8 vs. -0.2;
      P = 0.02), but magnitude of change was not clinically significant. Findings
      persisted across all prespecified subgroups. CONCLUSIONS: Intensive BP control in
      the ACCORD trial did not have a clinically significant impact, either positive or
      negative, on depression or patient-reported HRQL.

PMID- 22584135
TI  - Severe hypoglycemia and cardiovascular disease incidence in type 1 diabetes: the
      EURODIAB Prospective Complications Study.
AB  - OBJECTIVE: Frequent episodes of severe hypoglycemia may increase the risk of
      cardiovascular disease (CVD) in people with diabetes. Our aim was to study the
      relationship between severe hypoglycemic episodes and CVD incidence in subjects
      with type 1 diabetes, and further, to assess if markers of
      inflammation/endothelial injury were enhanced in individuals who experienced
      hypoglycemic episodes. RESEARCH DESIGN AND METHODS: The prospective study
      included 2,181 type 1 diabetic patients from the EURODIAB Prospective
      Complications Study. At baseline, frequency of self-reported severe hypoglycemia,
      defined as episodes serious enough to require the help of another person, was
      assessed based on responses to a patient questionnaire. Both fatal/nonfatal CVD
      was assessed 7.3 years after baseline examination. At the follow-up visit, data
      on both severe and nonsevere hypoglycemic episodes in the previous year were
      collected through a questionnaire and markers of inflammation/stress
      response/endothelial injury measured by enzyme-linked immunosorbent assays in the
      531 subjects of the nested case-control study, including 363 case subjects with
      one or more complications of diabetes and 168 control subjects with no evidence
      of any complication. RESULTS: During the follow-up period, 176 patients had
      incident CVD. Logistic regression analysis showed that severe hypoglycemia at the
      baseline examination was not associated with incidence of CVD (adjusted odds
      ratios [95% CI]: one to two episodes, 0.87 [0.55-1.37]; three or more episodes,
      1.09 [0.68-1.75]). Furthermore, follow-up serum levels of markers of endothelial
      damage/inflammation were not cross-sectionally associated with the frequency of
      hypoglycemic episodes. CONCLUSIONS: Taken together our data do not support the
      hypothesis that in type 1 diabetes, severe hypoglycemia increases the risk of
      CVD.

PMID- 22584138
TI  - PCR-electrospray ionization mass spectrometry: the potential to change infectious
      disease diagnostics in clinical and public health laboratories.
AB  - During the past 20 years, microbial detection methods that are genetically based,
      such as real-time PCR and peptide nucleic acid fluorescent hybridization,
      coexisted with traditional microbiological methods and were typically based on
      the identification of individual genetic targets. For these methods to be
      successful, a potential cause of infection must be suspected. More recently,
      multiplex PCR and multiplex RT-PCR were used to enable more broad-range testing
      based on panels of suspected pathogens. PCR-electrospray ionization mass
      spectrometry (PCR-ESI/MS) has emerged as a technology that is capable of
      identifying nearly all known human pathogens either from microbial isolates or
      directly from clinical specimens. Assay primers are strategically designed to
      target one or more of the broad pathogen categories: bacterial, mycobacterial,
      fungal, or viral. With broad-range amplification followed by detection of mixed
      amplicons, the method can identify genetic evidence of known and unknown
      pathogens. This unique approach supports a higher form of inquiry, asking the
      following question: What is the genetic evidence of known or unknown pathogens in
      the patient sample? This approach has advantages over traditional assays that
      commonly target the presence or absence of one or more pathogens with known
      genetic composition. This review considers the breadth of the published
      literature and explores the possibilities, advantages, and limitations for
      implementation of PCR-ESI/MS in diagnostic laboratories.

PMID- 22584136
TI  - Plasma fatty acid-binding protein 4, nonesterified fatty acids, and incident
      diabetes in older adults.
AB  - OBJECTIVE: To examine the relation of fatty acid-binding protein (FABP)4 and
      nonesterified fatty acids (NEFAs) to diabetes in older adults. RESEARCH DESIGN
      AND METHODS: We ascertained incident diabetes among 3,740 Cardiovascular Health
      Study participants (1992-2007) based on the use of hypoglycemic medications,
      fasting glucose >= 126 mg/dL, or nonfasting glucose >= 200 mg/dL. FABP4 and NEFA
      were measured on specimens collected between 1992 and 1993. RESULTS: Mean age of
      the 3,740 subjects studied was 74.8 years. For each SD increase in log FABP4,
      hazard ratios (HRs) for diabetes were 1.35 (95% CI 1.10-1.65) for women and 1.45
      (1.13-1.85) for men controlling for age, race, education, physical activity,
      cystatin C, alcohol intake, smoking, self-reported health status, and estrogen
      use for women (P for sex-FABP4 interaction 0.10). BMI modified the FABP4-diabetes
      relation (P = 0.009 overall; 0.02 for women and 0.135 for men), in that
      statistically significant higher risk of diabetes was mainly seen in men with BMI
      <25 kg/m(2) (HR per SD: 1.78 [95% CI 1.13-2.81]). There was a modest and
      nonsignificant association of NEFA with diabetes (P(trend) = 0.21). However, when
      restricted to the first 5 years of follow-up, multivariable-adjusted HRs for
      diabetes were 1.0 (ref.), 1.68 (95% CI 1.12-2.53), and 1.63 (1.07-2.50) across
      consecutive tertiles of NEFA (P(trend) = 0.03). CONCLUSIONS: Plasma FABP4 was
      positively associated with incident diabetes in older adults, and such
      association was statistically significant in lean men only. A significant
      positive association between plasma NEFA and incident diabetes was observed
      during the first 5 years of follow-up.

PMID- 22584132
TI  - Sequential intensification of metformin treatment in type 2 diabetes with
      liraglutide followed by randomized addition of basal insulin prompted by A1C
      targets.
AB  - OBJECTIVE: We evaluated the addition of liraglutide to metformin in type 2
      diabetes followed by intensification with basal insulin (detemir) if glycated
      hemoglobin (A1C) >=7%. RESEARCH DESIGN AND METHODS: In 988 participants from
      North America and Europe uncontrolled on metformin +/- sulfonylurea, sulfonylurea
      was discontinued and liraglutide 1.8 mg/day added for 12 weeks (run-in).
      Subsequently, those with A1C >=7% were randomized 1:1 to 26 weeks' open-label
      addition of insulin detemir to metformin + liraglutide (n = 162) or continuation
      without insulin detemir (n = 161). Patients achieving A1C <7% continued unchanged
      treatment (observational arm). The primary end point was A1C change between
      randomized groups. RESULTS: Of 821 participants completing the run-in, 61% (n =
      498) achieved A1C <7% (mean change -1.3% from 7.7% at start), whereas 39% (n =
      323) did not (-0.6% from 8.3% at start). During run-in, 167 of 988 (17%)
      withdrew; 46% of these due to gastrointestinal adverse events. At week 26, A1C
      decreased further, by 0.5% (from 7.6% at randomization) with insulin detemir (n =
      162) versus 0.02% increase without insulin detemir (n = 157) to 7.1 and 7.5%,
      respectively (estimated treatment difference -0.52 [95% CI -0.68 to -0.36]; P <
      0.0001). Forty-three percent of participants with insulin detemir versus 17%
      without reached A1C <7%. Mean weight decreased by 3.5 kg during run-in, then by
      0.16 kg with insulin detemir or 0.95 kg without insulin detemir. In the
      randomized phase, no major hypoglycemia occurred and minor hypoglycemia rates
      were 0.286 and 0.029 events per participant-year with and without insulin detemir
      (9.2 vs. 1.3%). CONCLUSIONS: Supplementation of metformin with liraglutide and
      then insulin detemir was well tolerated in the majority of patients, with good
      glycemic control, sustained weight loss, and very low hypoglycemia rates.

PMID- 22584139
TI  - Multicenter evaluation of the LightCycler MRSA advanced test, the Xpert MRSA
      Assay, and MRSASelect directly plated culture with simulated workflow comparison
      for the detection of methicillin-resistant Staphylococcus aureus in nasal swabs.
AB  - Rapid detection of nasal colonization with methicillin-resistant Staphylococcus
      aureus (MRSA) followed by appropriate infection control procedures reduces MRSA
      infection and transmission. We compared the performance and workflow of two Food
      and Drug Administration-approved nucleic acid amplification assays, the
      LightCycler MRSA Advanced Test and the Xpert MRSA test, with those of directly
      plated culture (MRSASelect) using 1202 nasal swabs collected at three U.S. sites.
      The sensitivity of the LightCycler test (95.2%; 95% CI, 89.1% to 98.4%) and Xpert
      assay (99%; 95% CI, 94.8% to 100%) did not differ compared with that of culture;
      the specificity of the two assays was identical (95.5%; 95% CI, 94.1% to 96.7%)
      compared with culture. However, sequencing performed on 71 samples with
      discordant results among the three methods confirmed the presence of MRSA in 40%
      of samples that were positive by both molecular methods but negative by culture.
      Workflow analysis from all sites including batch runs revealed average hands-on
      sample preparation times of 1.40, 2.35, and 1.44 minutes per sample for the
      LightCycler, Xpert, and MRSASelect methods, respectively. Discrete event
      simulation analysis of workflow efficiencies revealed that the LightCycler test
      used less hands-on time for the assay when greater than eight batched samples
      were run. The high sensitivity and specificity, low hands-on time, and efficiency
      gains using batching capabilities make the LightCycler test suitable for rapid
      batch screening of MRSA colonization.

PMID- 22584140
TI  - Molecular evolution and epidemiology of four serotypes of dengue virus in
      Thailand from 1973 to 2007.
AB  - Thailand was a hyper-endemic country for dengue with co-circulation of four
      serotypes and tens of thousands of infected cases annually. Taking into
      consideration the large number of local dengue virus (DENV) sequences available
      in GenBank, Thailand was the most ideal locality to study co-evolution of DENV.
      Therefore, we undertook a large-scale molecular epidemiological analysis of all
      DENV strains isolated in Thailand. In this study, we demonstrated that DENV
      strains of four serotypes post-1990 grouped into distinct clades, and that
      specific mutations in the envelope protein were first confirmed in these clades.
      Compared to the DENV1, DENV2 and DENV3 clades, the DENV4 clade evolved markedly
      more slowly (6.4 * 10-5 substitutions/site per year). Our results also showed
      that the genetic diversity of the predominant genotype of each serotype tended to
      slightly increase over time with fluctuating changes, followed by a stationary
      phase after 2000. This suggests that the four DENV clades became the predominant
      strains due to DENV possessing improved fitness after long-term selection.

PMID- 22584141
TI  - Ready, steady, go or just go? - The question of stabilization before transport
      for trauma victims.

PMID- 22584142
TI  - Simplifying clinical risk prediction for percutaneous coronary intervention of
      bifurcation lesions: the case for the ACEF (age, creatinine, ejection fraction)
      score.
AB  - AIMS: We aimed to appraise the predictive accuracy of a novel and user-friendly
      risk score, the ACEF (age, creatinine, ejection fraction), in patients undergoing
      PCI for coronary bifurcations. METHODS AND RESULTS: A multicentre, retrospective
      study was conducted enrolling consecutive patients undergoing bifurcation PCI
      between January 2002 and December 2006 in 22 Italian centres. Patients with
      complete data to enable computation of the ACEF score were divided into three
      groups according to tertiles of ACEF score. The primary endpoint was 30-day
      mortality. The discrimination of the ACEF score as a continuous variable was also
      appraised with area under the curve (AUC) of the receiver-operating
      characteristic. A total of 3,535 patients were included: 1,119 in the lowest
      tertile of ACEF score, 1,190 in the mid tertile, and 1,153 in the highest
      tertile. Increased ACEF score was associated with significantly different rates
      of 30-day mortality (0.1% in the lowest tertile vs. 0.5% in the mid tertile and
      3.0% in the highest tertile, p<0.001), with similar differences in myocardial
      infarction (0.3% vs. 0.7% and 1.8%, p<0.001) and major adverse cardiac events
      (MACE, 0.5% vs. 1.2% and 4.3%, p<0.001). After an average follow-up of 24.4+/
      15.1 months, increased ACEF score was still associated with a higher rate of all
      cause death (1.3% vs. 2.4% and 11.0%, p<0.001), cardiac death (0.9% vs. 1.4% and
      7.2%, p<0.001), myocardial infarction (3.4% vs. 2.7% and 5.7%, p<0.001), MACE
      (13.6% vs. 15.9% and 22.3%, p<0.001), and stent thrombosis (2.3% vs. 1.8% and
      5.0%, p<0.001). Discrimination of ACEF score was satisfactory for 30-day
      mortality (AUC=0.82 [0.77-0.87], p<0.001), 30-day MACE (AUC=0.73 [0.67-0.78],
      p<0.001), long-term mortality (AUC=0.77 [0.74-0.81], p<0.001), and moderate for
      long-term MACE (AUC=0.60 [0.57-0.62], p<0.001). CONCLUSIONS: The simple and
      extremely user-friendly ACEF score can accurately identify patients undergoing
      PCI for coronary bifurcation lesions at high risk of early fatal or non-fatal
      complications, as well as long-term fatality.

PMID- 22584143
TI  - The glycine deportation system and its pharmacological consequences.
AB  - The glycine deportation system is an essential component of glycine catabolism in
      man whereby 400 to 800mg glycine per day are deported into urine as hippuric
      acid. The molecular escort for this deportation is benzoic acid, which derives
      from the diet and from gut microbiota metabolism of dietary precursors. Three
      components of this system, involving hepatic and renal metabolism, and renal
      active tubular secretion help regulate systemic and central nervous system levels
      of glycine. When glycine levels are pathologically high, as in congenital
      nonketotic hyperglycinemia, the glycine deportation system can be upregulated
      with pharmacological doses of benzoic acid to assist in normalization of glycine
      homeostasis. In congenital urea cycle enzymopathies, similar activation of the
      glycine deportation system with benzoic acid is useful for the excretion of
      excess nitrogen in the form of glycine. Drugs which can substitute for benzoic
      acid as substrates for the glycine deportation system have adverse reactions that
      may involve perturbations of glycine homeostasis. The cancer chemotherapeutic
      agent ifosfamide has an unacceptably high incidence of encephalopathy. This would
      appear to arise as a result of the production of toxic aldehyde metabolites which
      deplete ATP production and sequester NADH in the mitochondrial matrix, thereby
      inhibiting the glycine deportation system and causing de novo glycine synthesis
      by the glycine cleavage system. We hypothesize that this would result in
      hyperglycinemia and encephalopathy. This understanding may lead to novel
      prophylactic strategies for ifosfamide encephalopathy. Thus, the glycine
      deportation system plays multiple key roles in physiological and
      neurotoxicological processes involving glycine.

PMID- 22584148
TI  - The practical nurse: a case for COMFORT communication training.
AB  - Licensed practical nurses provide the majority of bedside care in long-term care
      facilities and home care settings, and their communication with patients and
      families is pivotal to interventions aimed at reducing burdensome transitions to
      acute care settings. Although good communication skills are required for
      practical nurses, they receive limited instruction in their training. The goal of
      this study was to assess the effects of communication training for the practical
      nurse. A pre-post survey design was used to assess the COMFORT communication
      training curriculum provided to licensed practical nursing students. A comparison
      of mean scores on communication skills attitudes and perceived nursing competency
      revealed statistically significant improvement in attitudes and self-efficacy.
      This study shows promise for the feasibility and utilization of the COMFORT
      curriculum for nurse communication training. Further research should address the
      nurse's ability to perform COMFORT communication skills in the clinical setting.

PMID- 22584147
TI  - Vasculopathy related to manic/hypomanic symptom burden and first-generation
      antipsychotics in a sub-sample from the collaborative depression study.
AB  - BACKGROUND: Mood disorders substantially increase the risk of cardiovascular
      disease, though the mechanisms are unclear. We assessed for a dose-dependent
      relationship between course of illness or treatment with vasculopathy in a well
      characterized cohort. METHODS: Participants with mood disorders were recruited
      for the National Institute of Mental Health Collaborative Depression Study (CDS)
      and followed prospectively. A cross-sectional metabolic and vascular function
      evaluation was performed on a sub-sample near completion after a mean follow-up
      of 27 years. RESULTS: A total of 35 participants from the University of Iowa (33)
      and Washington University (2) sites of the CDS consented to a metabolic and
      vascular function assessment at the Iowa site. In multivariate linear regression,
      controlling for age, gender, and smoking, manic/hypomanic, but not depressive,
      symptom burden was associated with lower flow-mediated dilation. Cumulative
      exposure to antipsychotics and mood stabilizers was associated with elevated
      augmentation pressure and mean aortic systolic blood pressure. This appeared
      specifically related to first-generation antipsychotic exposure and mediated by
      increases in brachial systolic pressure. Although second-generation
      antipsychotics were associated with dyslipidemia and insulin resistance, they
      were not associated with vasculopathy. CONCLUSIONS: These results provide
      evidence that chronicity of mood symptoms contribute to vasculopathy in a dose
      dependent fashion. Patients with more manic/hypomanic symptoms had poorer
      endothelial function. First-generation antipsychotic exposure was associated with
      arterial stiffness, evidenced by higher augmentation pressure, perhaps secondary
      to elevated blood pressure. Vascular phenotyping methods may provide a promising
      means of elucidating the mechanisms linking mood disorders to vascular disease.

PMID- 22584149
TI  - Effect of a compassion-focused training program in palliative care education for
      medical students.
AB  - BACKGROUND: Compassion is the key value of humanities perspective. Little is
      known, however, concerning the impact of enhancing compassion on ethical decision
      making in end-of-life care. METHODS: A total of 251 preclinical medical students
      were enrolled in a palliative care training course. A structured self-report
      questionnaire was administered before and after training. RESULTS: Experience
      with caring for patients with terminal cancer was positively related to
      improvement in the decision of "truth telling is helpful to a good death." In
      addition, improvement in the perception of "compassionate care" was correlated
      with higher improvement in the decision of "discharge planning and home care."
      CONCLUSION: Compassion-focused training program can be helpful to improve medical
      students' competence in making more appropriate ethical decisions in end-of-life
      care.

PMID- 22584150
TI  - Factors and structural model related to end-of-life nursing care in general ward
      in Japan.
AB  - This study aimed to determine the factors related to the implementation of end-of
      life nursing care in general wards and to examine the adequacy of the
      hypothetical care implementation model. A cross-sectional survey was conducted.
      As the results of multiple regression analysis, 8 factors were determined:
      subjective evaluation of nurses' own team, positive attitudes toward caring for
      dying persons, existence of a role model, death relief (Death Attitude
      Inventory), knowledge of symptom management knowledge of family assessment,
      abstract judgment skill, and participation in the seminar. The hypothetical model
      was constructed using these factors, and the adequacy of this model was confirmed
      by a structural equation modeling. These factors and the model would give
      suggestions of educational content and its method, which should be provided to
      general ward nurses.

PMID- 22584151
TI  - Evaluation of end-of-life cancer care in the ICU: perceptions of the bereaved
      family in Japan.
AB  - The purpose of this study was to investigate the evaluation of end-of-life care
      from bereaved family of cancer patients who had died in intensive care units in
      Japan. Cross-sectional anonymous questionnaire surveys were conducted on
      community dwelling individuals aged 40-79 who were randomly sampled from census
      tracts. End-of-life care was assessed using the Good Death Inventory and Care
      Evaluation Scale. The respondents were 4011 bereaved family and response rate was
      40%. Of 390 respondents had experienced bereavement in intensive care unit. Of
      152 respondents had lost a loved one due to cancer. The result showed that
      bereaved family of cancer patients evaluated lower than the non-cancer patients
      for "The doctors dealt promptly with discomforting symptoms of the patients'
      (p=0.009), 'The nurses had adequate knowledge and skills' (p=0.016), 'Admission
      (use) was possible when necessary without waiting' (p=0.008) , Consideration was
      given to the health of the family (P=0.039) and Physical and psychological
      comfort (p=0.03). Overall, it can be presumed that the cancer patients' bereaved
      family evaluated about symptoms management and doctors and nurses skills was low.
      There is a need to improve for end-of-life care of cancer patients and to conduct
      further research to explore quality-improvement interventions to bereaved family
      of cancer in intensive care unit.

PMID- 22584144
TI  - Large conductance, calcium- and voltage-gated potassium (BK) channels: regulation
      by cholesterol.
AB  - Cholesterol (CLR) is an essential component of eukaryotic plasma membranes. CLR
      regulates the membrane physical state, microdomain formation and the activity of
      membrane-spanning proteins, including ion channels. Large conductance, voltage-
      and Ca2+-gated K+ (BK) channels link membrane potential to cell Ca2+ homeostasis.
      Thus, they control many physiological processes and participate in
      pathophysiological mechanisms leading to human disease. Because plasmalemma BK
      channels cluster in CLR-rich membrane microdomains, a major driving force for
      studying BK channel-CLR interactions is determining how membrane CLR controls the
      BK current phenotype, including its pharmacology, channel sorting, distribution,
      and role in cell physiology. Since both BK channels and CLR tissue levels play a
      pathophysiological role in human disease, identifying functional and structural
      aspects of the CLR-BK channel interaction may open new avenues for therapeutic
      intervention. Here, we review the studies documenting membrane CLR-BK channel
      interactions, dissecting out the many factors that determine the final BK current
      response to changes in membrane CLR content. We also summarize work in
      reductionist systems where recombinant BK protein is studied in artificial lipid
      bilayers, which documents a direct inhibition of BK channel activity by CLR and
      builds a strong case for a direct interaction between CLR and the BK channel
      forming protein. Bilayer lipid-mediated mechanisms in CLR action are also
      discussed. Finally, we review studies of BK channel function during
      hypercholesterolemia, and underscore the many consequences that the CLR-BK
      channel interaction brings to cell physiology and human disease.

PMID- 22584152
TI  - Electron microscopy of biotinylated protein complexes bound to streptavidin
      monolayer crystals.
AB  - Chemical biotinylation of protein complexes followed by binding to two
      dimensional (monolayer) crystals of streptavidin is shown to be an effective way
      to prepare cryo-EM specimens from samples at low protein concentration. Three
      different multiprotein complexes are used to demonstrate the generality of this
      method. In addition, native thermosomes, purified from Sulfolobus solfataricus
      P2, are used to demonstrate that a uniform distribution of Euler angles is
      produced, even though this particle is known to adopt a preferred orientation
      when other methods of cryo-EM specimen preparation are used.

PMID- 22584153
TI  - Timing of arteriovenous fistula placement and Medicare costs during dialysis
      initiation.
AB  - BACKGROUND/AIMS: Arteriovenous fistulas (AVFs) appear to be clinically superior
      to catheters as vascular access for maintenance hemodialysis, but higher
      insertion costs and high disease burden and mortality obscure the issue of
      whether AVF placement before hemodialysis initiation represents a net cost
      savings. We aimed to investigate Medicare costs for patients beginning
      maintenance hemodialysis, as related to timing of AVF placement. METHODS: Data
      were from Medicare claims for incident hemodialysis patients aged >=67 years in
      2006. The study period extended from 2 years before to 1 year after dialysis
      initiation. Patients identified as having AVFs were categorized by timing of
      placement (mature AVF at dialysis initiation, maturing AVF at initiation,
      postinitiation AVF placement). Because timing may be influenced by factors that
      also influence overall costs, the model accounted for this nonrandom treatment
      assignment. An ordered probit extension of the classic Heckman correction was
      employed after identifying an appropriate instrumental variable. A cohort with
      Medicare coverage before and after dialysis initiation was identified, and
      Medicare claims were used to identify comorbid conditions and treatment costs.
      RESULTS: Principal findings are that earlier AVF placement leads to lower costs,
      with the potential for about USD 500 million in savings. Additionally, the effect
      of nonrandom treatment assignment is real and significant. In our data, the
      impact of AVF placement timing was understated when treatment selection was
      ignored. CONCLUSIONS: For appropriate AVF candidates, having a mature AVF in
      place at the time of dialysis initiation appears to confer cost savings.

PMID- 22584154
TI  - High-density lipoprotein cholesterol subfractions HDL2 and HDL3 are reduced in
      women with rheumatoid arthritis and may augment the cardiovascular risk of women
      with RA: a cross-sectional study.
AB  - INTRODUCTION: Higher levels of high density lipoprotein (HDL) subfractions HDL3
      chol and particularly HDL2-chol protect against cardiovascular disease (CVD), but
      inflammation reduces the HDL level and may impair its anti-atherogenic effect.
      Changed HDL composition through the impact of inflammation on HDL subfractions
      may contribute to the excess risk of CVD in rheumatoid arthritis (RA). In this
      study, we investigated whether HDL2-chol and HDL3-chol concentrations differ
      between RA patients and healthy controls, and whether these levels are related to
      the level of RA disease activity. METHODS: Non-fasting blood samples were
      collected from 45 RA patients and 45 healthy controls. None of the participants
      had a history of CVD, diabetes, or used lipid-lowering drugs. HDL2-chol and HDL3
      chol concentrations were obtained by ultracentrifugation. Regression modeling was
      used to compare HDL subfraction levels between RA patients and healthy controls,
      and to analyze the effect of disease activity on HDL2-chol and HDL3-chol.
      RESULTS: HDL2-chol and HDL3-chol were significantly lower in RA patients compared
      to healthy controls (P = 0.01, P = 0.005, respectively). The HDL2:HDL3 ratio was
      significantly lower in patients compared to controls (P = 0.04). Reduced HDL2
      chol and HDL3-chol levels were primarily present in female RA patients and not in
      male RA patients. A modest effect of the disease activity score in 28 joins (
      DAS28) on HDL2-chol concentrations was found, after correction for disease
      duration, glucocorticosteroid use and body mass index (BMI), with a 0.06 mmol/L
      decrease with every point increase in DAS28 (P = 0.05). DAS28 did not
      significantly affect HDL3-chol concentrations (P = 0.186). CONCLUSIONS: Both HDL
      subfractions but particularly HDL2-chol concentrations were decreased in RA,
      primarily in women. This seems to be associated with disease activity and is of
      clinical relevance. The reduction of the HDL subfraction concentrations,
      particularly the supposedly beneficial HDL2-chol, may negatively impact the
      cardiovascular risk profile of women with RA.

PMID- 22584155
TI  - HLA class I sequence-based typing using DNA recovered from frozen plasma.
AB  - We describe a rapid, reliable and cost-effective method for intermediate-to-high
      resolution sequence-based HLA class I typing using frozen plasma as a source of
      genomic DNA. The plasma samples investigated had a median age of 8.5 years. Total
      nucleic acids were isolated from matched frozen PBMC (~2.5 million) and plasma
      (500 MUl) samples from a panel of 25 individuals using commercial silica-based
      kits. Extractions yielded median [IQR] nucleic acid concentrations of 85.7 [47.0
      130.0]ng/MUl and 2.2 [1.7-2.6]ng/MUl from PBMC and plasma, respectively.
      Following extraction, ~1000 base pair regions spanning exons 2 and 3 of HLA-A, -B
      and -C were amplified independently via nested PCR using universal, locus
      specific primers and sequenced directly. Chromatogram analysis was performed
      using commercial DNA sequence analysis software and allele interpretation was
      performed using a free web-based tool. HLA-A, -B and -C amplification rates were
      100% and chromatograms were of uniformly high quality with clearly
      distinguishable mixed bases regardless of DNA source. Concordance between PBMC
      and plasma-derived HLA types was 100% at the allele and protein levels. At the
      nucleotide level, a single partially discordant base (resulting from a failure to
      call both peaks in a mixed base) was observed out of >46,975 bases sequenced
      (>99.9% concordance). This protocol has previously been used to perform HLA class
      I typing from a variety of genomic DNA sources including PBMC, whole blood,
      granulocyte pellets and serum, from specimens up to 30 years old. This method
      provides comparable specificity to conventional sequence-based approaches and
      could be applied in situations where cell samples are unavailable or DNA
      quantities are limiting.

PMID- 22584156
TI  - Optimization and application of a flow cytometric PU.1 assay for murine immune
      cells.
AB  - PU.1 is a master transcription factor whose levels directly influence
      hematopoiesis, leukemia, susceptibility to sepsis, and macrophage function.
      Though measurement of PU.1 levels is important to health and disease, most
      studies have relied on PCR or western blots to measure the expression of this
      transcription factor. An accessible, validated assay that could measure PU.1
      protein in subpopulations of cells is needed. In this work we present an
      optimized flow cytometric assay to detect PU.1 in subpopulations of immune cells.
      Murine myeloid cells were fixed in paraformaldehyde, permeabilized, and then
      stained with anti PU.1 in the presence and absence of a blocking peptide
      containing the binding site of the antibody. The bound anti PU.1 was then
      visualized with a labeled second antibody. Methanol and ethanol were tested for
      their relative ability to permeabilize cells and detect PU.1. The effect of the
      procedure upon the ability to detect cellular subpopulations was examined.
      Relative PU.1 1evels in normal T cells, B cells, monocytes, macrophages,
      dendritic cells, neutrophils, and progenitors from the spleen and/or bone marrow
      were determined. Finally, PU.1 levels in proliferating myeloid cells from burn
      mice were determined. There was a dose dependent increase in the amount of PU.1
      detected with increasing amounts of PU.1 antibody that was not seen when blocking
      peptide was used. Methanol or ethanol gave equivalent results as permeabilization
      agents, but the latter allowed easier detection of surface antigens when surface
      staining was performed prior to permeabilization. T cells had little if any PU.1,
      while B cells had intermediate levels of PU.1, and myeloid cells had high levels
      of PU.1. Monocytes had higher levels of PU.1 than did neutrophils or spleen
      macrophages. Plasmacytoid dendritic cells had lower levels of PU.1 than did
      conventional dendritic cells. Immature myeloid cells had higher levels of PU.1
      than did mature myeloid cells. In addition, PU.1 levels were higher in
      proliferating cells than the corresponding non proliferating cells. Myeloid cells
      derived from burn mice tended to have higher levels of PU.1 than did unburned,
      but proliferating cells from burn or sham mice showed no difference in their
      levels of PU.1. This assay should be a useful addition to the tools used to study
      the function of PU.1 in health and disease.

PMID- 22584157
TI  - Parkinson disease: Scales to detect depression in Parkinson disease.

PMID- 22584159
TI  - Multiple sclerosis: characterization of lesion evolution in relapsing-remitting
      and secondary progressive multiple sclerosis.

PMID- 22584160
TI  - Neuro-oncology: MicroRNAs in CSF-biomarkers of brain cancers and disease
      activity.

PMID- 22584158
TI  - Olfactory dysfunction in Parkinson disease.
AB  - Olfactory dysfunction is among the earliest nonmotor features of Parkinson
      disease (PD). Such dysfunction is present in approximately 90% of early-stage PD
      cases and can precede the onset of motor symptoms by years. The mechanisms
      responsible for olfactory dysfunction are currently unknown. As equivalent
      deficits are observed in Alzheimer disease, Down syndrome, and the Parkinson
      dementia complex of Guam, a common pathological substrate may be involved. Given
      that olfactory loss occurs to a lesser extent or is absent in disorders such as
      multiple system atrophy, corticobasal degeneration, and progressive supranuclear
      palsy, olfactory testing can be useful in differential diagnosis. The olfactory
      dysfunction in PD and a number of related diseases with smell loss correlates
      with decreased numbers of neurons in structures such as the locus coeruleus, the
      raphe nuclei, and the nucleus basalis of Meynart. These neuroanatomical findings,
      together with evidence for involvement of the autonomic nervous system in
      numerous PD-related symptoms, suggest that deficits in cholinergic, noradrenergic
      and serotonergic function may contribute to the olfactory loss. This Review
      discusses the current understanding of olfactory dysfunction in PD, including
      factors that may be related to its cause.

PMID- 22584161
TI  - Molecular characterization of the regenerative response induced by intrarenal
      transplantation of selected renal cells in a rodent model of chronic kidney
      disease.
AB  - Dedifferentiation and proliferation of resident tubular epithelial cells is a
      mechanism of action potentially contributing to repair and regeneration in
      kidneys presenting with ischemic or chronic disease. To more efficiently develop
      cell and tissue engineering technologies for the kidney, we have developed
      molecular assays to evaluate the acquisition of a pluripotent state associated
      with stem/progenitor cell phenotype during induction of a regenerative response
      within the kidneys of rats with chronic kidney disease (CKD) following
      therapeutic intervention. Intrarenal delivery of selected bioactive renal cells
      leads to significant upregulation of pluripotency-associated SOX2 mRNA within the
      diseased kidney tissue from 1 to 24 weeks after treatment. The overall
      regenerative response index was assessed by quantitative composite expression of
      CD24, NODAL and LEFTY1 proteins, which were induced within 1 week of cell
      treatment and peaked at 12 weeks after treatment, reaching statistical
      significance (p < 0.05) compared to untreated CKD controls. Molecular assays that
      incorporate the assessment of SOX2 and the regenerative response index may prove
      to be valuable tools for the detection and monitoring of the tissue response
      after the delivery of regenerative treatments for CKD, thereby significantly
      shortening the developmental timelines associated with such therapies.

PMID- 22584162
TI  - Evaluating iPhone recordings for acoustic voice assessment.
AB  - AIMS: This study examined the viability of using iPhone recordings for acoustic
      measurements of voice quality. METHODS: Acoustic measures were compared between
      voice signals simultaneously recorded from 11 normal speakers (6 females and 5
      males) through an iPhone (model A1303, Apple, USA) and a comparison recording
      system. Comparisons were also conducted between the pre- and post-operative
      voices recorded from 10 voice patients (4 females and 6 males) through the
      iPhone. Participants aged between 27 and 79 years. RESULTS: Measures from iPhone
      and comparison signals were found to be highly correlated. Findings of the
      effects of vowel type on the selected measures were consistent between the two
      recording systems and congruent with previous findings. Analysis of the patient
      data revealed that a selection of acoustic measures, such as vowel space area and
      voice perturbation measures, consistently demonstrated a positive change
      following phonosurgery. CONCLUSION: The present findings indicated that the
      iPhone device tested was useful for tracking voice changes for clinical
      management. Preliminary findings regarding factors such as gender and type of
      pathology suggest that intra-subject, instead of norm-referenced, comparisons of
      acoustic measures would be more useful in monitoring the progression of a voice
      disorder or tracking the treatment effect.

PMID- 22584164
TI  - A software tool for stitching two PET/CT body segments into a single whole-body
      image set.
AB  - A whole-body PET/CT scan extending from the vertex of the head to the toes of the
      patient is not feasible on a number of commercially available PET/CT scanners due
      to a limitation in the extent of bed travel on these systems. In such cases, the
      PET scan has to be divided into two parts: one covering the upper body segment,
      while the other covering the lower body segment. The aim of this paper is to
      describe and evaluate, using phantom and patient studies, a software tool that
      was developed to stitch two body segments and output a single whole-body image
      set, thereby facilitating the interpretation of whole-body PET scans. A
      mathematical model was first developed to stitch images from two body segments
      using three landmarks. The model calculates the relative positions of the
      landmarks on the two segments and then generates a rigid transformation that
      aligns these landmarks on the two segments. A software tool was written to
      implement this model while correcting for radioactive decay between the two body
      segments, and output a single DICOM whole-body image set with all the necessary
      tags. One phantom, and six patient studies were conducted to evaluate the
      performance of the software. In these studies, six radio-opaque markers (BBs)
      were used as landmarks (three on each leg). All studies were acquired in two body
      segments with BBs placed in the overlap region of the two segments. The PET/CT
      images of each segment were then stitched using the software tool to create a
      single DICOM whole-body PET/CT image. Evaluation of the stitching tool was based
      on visual inspection, consistency of radiotracer uptake in the two segments, and
      ability to display the resultant DICOM image set on two independent workstations.
      The software tool successfully stitched the two segments of the phantom image,
      and generated a single whole-body DICOM PET/CT image set that had the correct
      alignment and activity concentration throughout the image. The stitched images
      were viewed by two independent workstations from two different manufacturers,
      attesting the ability of the software tool to produce a DICOM compliant image
      set. The study demonstrated that this software tool allows the stitching of two
      segments of a whole-body PET/CT scan with minimal user interaction, thereby
      facilitating the interpretation of whole body PET/CT scans from a number of
      scanners with limited extent of bed travel.

PMID- 22584163
TI  - alpha(V)beta(3) integrin-targeted PLGA-PEG nanoparticles for enhanced anti-tumor
      efficacy of a Pt(IV) prodrug.
AB  - Targeted delivery of therapeutics to tumor neovasculature is potentially a
      powerful approach for selective cancer treatment. Integrins are heterodimeric
      transmembrane proteins involved in cell adhesion and cell signaling, and their
      expression is commonly upregulated in cancers and inflammatory diseases. The
      alpha(v)beta(3) integrin is differentially upregulated on angiogenic endothelial
      cells as well as on many cancer cells. Here we demonstrate the differential
      targeting of cisplatin prodrug-encapsulated poly(d,l-lactic-co-glycolic acid)
      block-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) to the alpha(v)beta(3)
      integrin on cancer cells using the cyclic pentapeptide c(RGDfK). Cisplatin is one
      of the most widely used anticancer drugs, and approaches that can improve its
      therapeutic index are of broad importance. The RGD-targeted Pt(IV)-encapsulated
      NPs displayed enhanced cytotoxicity as compared to cisplatin administered in its
      conventional dosage form in model prostate and breast cancer epithelial cells in
      vitro. Cytotoxicities were also elevated in comparison to those of previously
      reported systems, a small molecule Pt(IV)-RGD conjugate and a Pt(IV) nanoscale
      coordination polymer carrying RGD moieties. This result encouraged us also to
      evaluate the anticancer effect of the new construct in an animal model. The RGD
      targeted PLGA-PEG NPs were more efficacious and better tolerated by comparison to
      cisplatin in an orthotopic human breast cancer xenograft model in vivo.

PMID- 22584165
TI  - Comparison of 16 mm OSU-Nag and COMS eye plaques.
AB  - OSU-NAG eye plaques use fewer sources than COMS-plaques of comparable size, and
      do not employ a Silastic seed carrier insert. Monte Carlo modeling was used to
      calculate 3D dose distributions for a 16 mm OSU-NAG eye plaque and a 16 mm COMS
      eye plaque loaded with either Iodine-125 or Cesium-131 brachytherapy sources. The
      OSU-NAG eye plaque was loaded with eight sources forming two squares, whereas the
      COMS eye plaque was loaded with thirteen sources approximating three isocentric
      circles. A spherical eyeball 24.6 mm in diameter and an ellipsoid-like tumor 6 mm
      in height and 12 mm in the major and minor axes were used to evaluate the doses
      delivered. To establish a fair comparison, a water seed carrier was used instead
      of the Silastic seed carrier designed for the traditional COMS eye plaque.
      Calculations were performed on the dose distributions along the eye plaque axis
      and the DVHs of the tumor, as well as the 3D distribution. Our results indicated
      that, to achieve a prescription dose of 85 Gy at 6 mm from the inner sclera edge
      for a six-day treatment, the OSU-NAG eye plaque will need 6.16 U/source and
      6.82U/source for 125I and 131Cs, respectively. The COMS eye plaque will require
      4.02 U/source and 4.43 U/source for the same source types. The dose profiles of
      the two types of eye plaques on their central axes are within 9% difference for
      all applicable distances. The OSU-NAG plaque delivers about 10% and 12% more dose
      than the COMS for 125I and 131Cs sources, respectively, at the inner sclera edge,
      but 6% and 3% less dose at the opposite retina. The DVHs of the tumor for two
      types of plaques were within 6% difference. In conclusion, the dosimetric quality
      of the OSU-NAG eye plaque used in eye plaque brachytherapy is comparable to the
      COMS eye plaque.

PMID- 22584167
TI  - Immobilization precision of a modified GTC frame.
AB  - The purpose of this study was to evaluate and quantify the interfraction
      reproducibility and intrafraction immobilization precision of a modified GTC
      frame. The error of the patient alignment and imaging systems were measured using
      a cranial skull phantom, with simulated, predetermined shifts. The kV setup
      images were acquired with a room-mounted set of kV sources and panels. Calculated
      translations and rotations provided by the computer alignment software relying
      upon three implanted fiducials were compared to the known shifts, and the
      accuracy of the imaging and positioning systems was calculated. Orthogonal kV
      setup images for 45 proton SRT patients and 1002 fractions (average 22.3
      fractions/patient) were analyzed for interfraction and intrafraction
      immobilization precision using a modified GTC frame. The modified frame employs a
      radiotransparent carbon cup and molded pillow to allow for more treatment angles
      from posterior directions for cranial lesions. Patients and the phantom were
      aligned with three 1.5 mm stainless steel fiducials implanted into the skull. The
      accuracy and variance of the patient positioning and imaging systems were
      measured to be 0.10 +/- 0.06 mm, with the maximum uncertainty of rotation being
      +/-0.07 degrees . 957 pairs of interfraction image sets and 974 intrafraction
      image sets were analyzed. 3D translations and rotations were recorded. The 3D
      vector interfraction setup reproducibility was 0.13 mm +/- 1.8 mm for
      translations and the largest uncertainty of +/- 1.07o for rotations. The
      intrafraction immobilization efficacy was 0.19 mm +/- 0.66 mm for translations
      and the largest uncertainty of +/- 0.50o for rotations. The modified GTC frame
      provides reproducible setup and effective intrafraction immobilization, while
      allowing for the complete range of entrance angles from the posterior direction.

PMID- 22584166
TI  - The effects of motion on the dose distribution of proton radiotherapy for
      prostate cancer.
AB  - Proton radiotherapy of the prostate basal or whole seminal vesicles using
      scattering delivery systems is an effective treatment of prostate cancer that has
      been evaluated in prospective trials. Meanwhile, the use of pencil beam scanning
      (PBS) can further reduce the dose in the beam entrance channels and reduce the
      dose to the normal tissues. However, PBS dose distributions can be affected by
      intra- and interfractional motion. In this treatment planning study, the effects
      of intra- and interfractional organ motion on PBS dose distributions are
      investigated using repeated CT scans at close and distant time intervals. The
      minimum dose (Dmin) and the dose to 2% and 98% of the volumes (D2% and D98%), as
      well as EUD in the clinical target volumes (CTV), is used as measure of
      robustness. In all patients, D98% was larger than 96% and D2% was less than 106%
      of the prescribed dose. The combined information from Dmin, D98% and EUD led to
      the conclusion that there are no relevant cold spots observed in any of the
      verification plans. Moreover, it was found that results of single field
      optimization are more robust than results from multiple field optimizations.

PMID- 22584168
TI  - Target localization using scanner-acquired SPECT data.
AB  - Target localization using single photon emission computed tomography (SPECT) and
      planar imaging is being investigated for guiding radiation therapy delivery.
      Previous studies on SPECT-based localization have used computer-simulated or
      hybrid images with simulated tumors embedded in disease-free patient images where
      the tumor position is known and localization can be calculated directly. In the
      current study, localization was studied using scanner-acquired images. Five
      fillable spheres were placed in a whole body phantom. Sphere-to-background 99mTc
      radioactivity was 6:1. Ten independent SPECT scans were acquired with a Trionix
      Triad scanner using three detector trajectories: left lateral 180 degrees , 360
      degrees , and right lateral 180 degrees . Scan time was equivalent to 4.5 min.
      Images were reconstructed with and without attenuation correction. True target
      locations were estimated from 12 hr SPECT and CT images. From the 12 hr SPECT
      scan, 45 sets of orthogonal planar images were used to assess target
      localization; total acquisition time per set was equivalent to 4.5min. A
      numerical observer localized the center of the targets in the 4.5 min SPECT and
      planar images. SPECT-based localization errors were compared for the different
      detector trajectories. Across the four peripheral spheres, and using optimal
      iteration numbers and postreconstruction smoothing, means and standard deviations
      in localization errors were 0.90 +/- 0.25 mm for proximal 180 degrees 
      trajectories, 1.31 +/- 0.51 mm for 360 degrees  orbits, and 3.93 +/- 1.48 mm for
      distal 180 degrees  trajectories. This rank order in localization performance is
      predicted by target attenuation and distance from the target to the collimator.
      For the targets with mean localization errors < 2 mm, attenuation correction
      reduced localization errors by 0.15 mm on average. The improvement from
      attenuation correction was 1.0 mm on average for the more poorly localized
      targets. Attenuation correction typically reduced localization errors, but for
      well-localized targets, the detector trajectory generally had a larger effect.
      Localization performance was found to be robust to iteration number and
      smoothing. Localization was generally worse using planar images as compared with
      proximal 180 degrees  and 360 degrees  SPECT scans. Using a proximal detector
      trajectory and attenuation correction, localization errors were within 2 mm for
      the three superficial targets, thus supporting the current role in biopsy and
      surgery, and demonstrating the potential for SPECT imaging inside radiation
      therapy treatment rooms.

PMID- 22584169
TI  - A study of surface dosimetry for breast cancer radiotherapy treatments using
      Gafchromic EBT2 film.
AB  - The present study quantified surface doses on several rectangular phantom setups
      and on curved surface phantoms for a 6 MV photon field using the Attix parallel
      plate chamber and Gafchromic EBT2 film. For the rectangular phantom setups, the
      surface doses on a homogenous water equivalent phantom and a water equivalent
      phantom with 60 mm thick lung equivalent material were measured. The measurement
      on the homogenous phantom setup showed consistency in surface and near-surface
      doses between an open field and enhanced dynamic wedge (EDW) fields, whereas
      physical wedged fields showed small differences. Surface dose measurements made
      using the EBT2 film showed good agreement with results of the Attix chamber and
      results obtained in previous studies which used other dosimeters within the
      measurement uncertainty of 3.3%. The surface dose measurements on the phantom
      setup with lung equivalent material showed a small increase without bolus and up
      to 6.9% increase with bolus simulating the increase of chest wall thickness.
      Surface doses on the cylindrical CT phantom and customized Perspex chest phantom
      were measured using the EBT2 film with and without bolus. The results indicate
      the important role of the presence of bolus if the clinical target volume (CTV)
      is quite close to the surface. Measurements on the cylindrical phantom suggest
      that surface doses at the oblique positions of 60 degrees  and 90 degrees  are
      mainly caused by the lateral scatter from the material inside the phantom. In the
      case of a single tangential irradiation onto Perspex chest phantom, the
      distribution of the surface dose with and without bolus materials showed opposing
      inclination patterns, whereas the dose distribution for two opposed tangential
      fields gave symmetric dose distribution. This study also demonstrates the
      suitability of Gafchromic EBT2 film for surface dose measurements in megavoltage
      photon beams.

PMID- 22584170
TI  - Clinical commissioning and use of the Novalis Tx linear accelerator for SRS and
      SBRT.
AB  - The purpose of this study was to perform comprehensive measurements and testing
      of a Novalis Tx linear accelerator, and to develop technical guidelines for com
      missioning from the time of acceptance testing to the first clinical treatment.
      The Novalis Tx (NTX) linear accelerator is equipped with, among other features, a
      high-definition MLC (HD120 MLC) with 2.5 mm central leaves, a 6D robotic couch,
      an optical guidance positioning system, as well as X-ray-based image guidance
      tools to provide high accuracy radiation delivery for stereotactic radiosurgery
      and stereotactic body radiation therapy procedures. We have performed extensive
      tests for each of the components, and analyzed the clinical data collected in our
      clinic. We present technical guidelines in this report focusing on methods for:
      (1) efficient and accurate beam data collection for commissioning treatment
      planning systems, including small field output measurements conducted using a
      wide range of detectors; (2) commissioning tests for the HD120 MLC; (3) data
      collection for the baseline characteristics of the on-board imager (OBI) and
      ExacTrac X-ray (ETX) image guidance systems in conjunction with the 6D robotic
      couch; and (4) end-to-end testing of the entire clinical process. Established
      from our clinical experience thus far, recommendations are provided for accurate
      and efficient use of the OBI and ETX localization systems for intra- and
      extracranial treatment sites. Four results are presented. (1) Basic beam data
      measurements: Our measurements confirmed the necessity of using small detectors
      for small fields. Total scatter factors varied significantly (30% to
      approximately 62%) for small field measurements among detectors. Unshielded
      stereotactic field diode (SFD) overestimated dose by ~ 2% for large field sizes.
      Ion chambers with active diameters of 6 mm suffered from significant volume
      averaging. The sharpest profile penumbra was observed for the SFD because of its
      small active diameter (0.6 mm). (2) MLC commissioning: Winston Lutz test,
      light/radiation field congruence, and Picket Fence tests were performed and were
      within criteria established by the relevant task group reports. The measured mean
      MLC transmission and dynamic leaf gap of 6 MV SRS beam were 1.17% and 0.36 mm,
      respectively. (3) Baseline characteristics of OBI and ETX: The isocenter
      localization errors in the left/right, posterior/anterior, and superior/inferior
      directions were, respectively, -0.2 +/- 0.2 mm, -0.8 +/- 0.2 mm, and -0.8 +/- 0.4
      mm for ETX, and 0.5 +/- 0.7 mm, 0.6 +/- 0.5 mm, and 0.0 +/- 0.5 mm for OBI cone
      beam computed tomography. The registration angular discrepancy was 0.1 +/- 0.2
      degrees , and the maximum robotic couch error was 0.2 degrees . (4) End-to-end
      tests: The measured isocenter dose differences from the planned values were 0.8%
      and 0.4%, measured respectively by an ion chamber and film. The gamma pass rate,
      measured by EBT2 film, was 95% (3% DD and 1 mm DTA). Through a systematic series
      of quantitative commissioning experiments and end-to-end tests and our initial
      clinical experience, described in this report, we demonstrate that the NTX is a
      robust system, with the image guidance and MLC requirements to treat a wide
      variety of sites - in particular for highly accurate delivery of SRS and SBRT
      based treatments.

PMID- 22584171
TI  - Skin dose during radiotherapy: a summary and general estimation technique.
AB  - The skin dose associated with radiotherapy may be of interest for clinical
      evaluation or investigating the risk of late effects. However, skin dose is not
      intuitive and is difficult to measure. Our objectives were to develop and
      evaluate a general estimation technique for skin dose based on treatment
      parameters. The literature on skin dose was supplemented with measurements and
      Monte Carlo simulations. Using all available data, a general dosimetry system was
      developed (in the form of a series of equations) to estimate skin dose based on
      treatment parameters including field size, the presence of a block tray, and
      obliquity of the treatment field. For out-of-field locations, the distance from
      the field edge was also considered. This dosimetry system was then compared to
      TLD measurements made on the surface of a phantom. As compared to measurements,
      the general dosimetry system was able to predict skin dose within, on average,
      21% of the local dose (4% of the Dmax dose). Skin dose for patients receiving
      radiotherapy can be estimated with reason-able accuracy using a set of general
      rules and equations.

PMID- 22584172
TI  - Monte Carlo study of a new I-125 brachytherapy prototype seed with a ceramic
      radionuclide carrier and radiographic marker.
AB  - In prostate cancer treatment, there is an increasing interest in the permanent
      radioactive seeds implant technique. Currently, in Brazil, the seeds are imported
      with high prices, which prohibit their use in public hospitals. A ceramic matrix
      that can be used as a radioisotope carrier and radiographic marker was developed
      at our institution. The ceramic matrix is distinguished by the characteristic of
      maintaining the radioactive material uniformly distributed in its surface. In
      this work, Monte Carlo simulations were performed in order to assess the dose
      distributions generated by this prototype seed model, with the ceramic matrix
      encapsulated in titanium, in the same way as the commercial 6711 seed. The
      obtained data was assessed, as described in the TG-43U1 report by the American
      Association of Physicists in Medicine, for two seed models: (1) the most used
      model 6711 source - for validation and comparison, and (2) for the prototype
      model with the ceramic matrix. The dosimetric parameters dose rate constant,
      Lambda, radial dose function, gL(r), and anisotropy function, F(r,theta), were
      derived from simulations by the Monte Carlo method using the MCNP5 code. A Lambda
      0.992 (+/- 2.33%) cGyh-1U-1 was found for the prototype model. In comparison with
      the 6711 model, a lower dose fall-off on transverse axis was found, as well as a
      lower dose anisotropy for the radius r = 0.25 cm. In general, for all distances,
      the prototype seed model presents a slightly larger anisotropy between 0 degrees 
      <= Theta < 50 degrees  and anisotropy similar to the 6711 model for Theta >= 50
      degrees . The dosimetric characteristics of the prototype model presented in this
      study suggest that its use is feasible. Because of the model's characteristics,
      seeds of lower specific activity iodine might be necessary which, on the other
      hand, would help to reduce costs. However, it has to be emphasized that the
      proposed source is a prototype, and the required (AAPM prerequisites)
      experimental study and tolerance manufacturer values are pending for future
      studies.

PMID- 22584173
TI  - In vivo dose measurement using TLDs and MOSFET dosimeters for cardiac
      radiosurgery.
AB  - In vivo measurements were made of the dose delivered to animal models in an
      effort to develop a method for treating cardiac arrhythmia using radiation. This
      treatment would replace RF energy (currently used to create cardiac scar) with
      ionizing radiation. In the current study, the pulmonary vein ostia of animal
      models were irradiated with 6 MV X-rays in order to produce a scar that would
      block aberrant signals characteristic of atrial fibrillation. The CyberKnife
      radiosurgery system was used to deliver planned treatments of 20-35 Gy in a
      single fraction to four animals. The Synchrony system was used to track
      respiratory motion of the heart, while the contractile motion of the heart was
      untracked. The dose was measured on the epicardial surface near the right
      pulmonary vein and on the esophagus using surgically implanted TLD dosimeters, or
      in the coronary sinus using a MOSFET dosimeter placed using a catheter. The doses
      measured on the epicardium with TLDs averaged 5% less than predicted for those
      locations, while doses measured in the coronary sinus with the MOSFET sensor
      nearest the target averaged 6% less than the predicted dose. The measurements on
      the esophagus averaged 25% less than predicted. These results provide an
      indication of the accuracy with which the treatment planning methods accounted
      for the motion of the target, with its respiratory and cardiac components. This
      is the first report on the accuracy of CyberKnife dose delivery to cardiac
      targets.

PMID- 22584174
TI  - On the quantification of the dosimetric accuracy of collapsed cone convolution
      superposition (CCCS) algorithm for small lung volumes using IMRT.
AB  - Specialized techniques that make use of small field dosimetry are common practice
      in today's clinics. These new techniques represent a big challenge to the
      treatment planning systems due to the lack of lateral electronic equilibrium.
      Because of this, the necessity of planning systems to overcome such difficulties
      and provide an accurate representation of the true value is of significant
      importance. Pinnacle3 is one such planning system. During the IMRT optimization
      process, Pinnacle3 treatment planning system allows the user to specify a minimum
      segment size which results in multiple beams composed of several subsets of
      different widths. In this study, the accuracy of the engine dose calculation,
      collapsed cone convolution superposition algorithm (CCCS) used by Pinnacle3, was
      quantified by Monte Carlo simulations, ionization chamber, and Kodak extended
      dose range film (EDR2) measurements for 11 SBRT lung patients. Lesions were < 3.0
      cm in maximal diameter and <27.0cm3 in volume. The Monte Carlo EGSnrc?BEAMnrc and
      EGS4?MCSIM were used in the comparison. The minimum segment size allowable during
      optimization had a direct impact on the number of monitor units calculated for
      each beam. Plans with the smallest minimum segment size (0.1 cm2 to 2.0 cm2) had
      the largest number of MUs. Although PTV coverage remained unaffected, the segment
      size did have an effect on the dose to the organs at risk. Pinnacle3-calculated
      PTV mean doses were in agreement with Monte Carlo-calculated mean doses to within
      5.6% for all plans. On average, the mean dose difference between Monte Carlo and
      Pinnacle3 for all 88 plans was 1.38%. The largest discrepancy in maximum dose was
      5.8%, and was noted for one of the plans using a minimum segment size of 1.0 cm2.
      For minimum dose to the PTV, a maximum discrepancy between Monte Carlo and
      Pinnacle3 was noted of 12.5% for a plan using a 6.0 cm2 minimum segment size.
      Agreement between point dose measurements and Pinnacle3-calculated doses were on
      average within 0.7% in both phantoms. The profiles show a good agreement between
      Pinnacle3, Monte Carlo, and EDR2 film. The gamma index and the isodose lines
      support the result.

PMID- 22584175
TI  - Optimal parameters for clinical implementation of breast cancer patient setup
      using Varian DTS software.
AB  - Digital tomosynthesis (DTS) was evaluated as an alternative to cone-beam computed
      tomography (CBCT) for patient setup. DTS is preferable when there are constraints
      with setup time, gantry-couch clearance, and imaging dose using CBCT. This study
      characterizes DTS data acquisition and registration parameters for the setup of
      breast cancer patients using nonclinical Varian DTS software. DTS images were
      reconstructed from CBCT projections acquired on phantoms and patients with
      surgical clips in the target volume. A shift-and-add algorithm was used for DTS
      volume reconstructions, while automated cross-correlation matches were performed
      within Varian DTS software. Triangulation on two short DTS arcs separated by
      various angular spread was done to improve 3D registration accuracy. Software
      performance was evaluated on two phantoms and ten breast cancer patients using
      the registration result as an accuracy measure; investigated parameters included
      arc lengths, arc orientations, angular separation between two arcs,
      reconstruction slice spacing, and number of arcs. The shifts determined from DTS
      to-CT registration were compared to the shifts based on CBCT-to-CT registration.
      The difference between these shifts was used to evaluate the software accuracy.
      After findings were quantified, optimal parameters for the clinical use of DTS
      technique were determined. It was determined that at least two arcs were
      necessary for accurate 3D registration for patient setup. Registration accuracy
      of 2 mm was achieved when the reconstruction arc length was > 5 degrees  for
      clips with HU >= 1000; larger arc length (>= 8 degrees ) was required for very
      low HU clips. An optimal arc separation was found to be >= 20 degrees  and
      optimal arc length was 10 degrees . Registration accuracy did not depend on DTS
      slice spacing. DTS image reconstruction took 10-30 seconds and registration took
      less than 20 seconds. The performance of Varian DTS software was found suitable
      for the accurate setup of breast cancer patients. Optimal data acquisition and
      registration parameters were determined.

PMID- 22584176
TI  - Study of ExacTrac X-ray 6D IGRT setup uncertainty for marker-based prostate IMRT
      treatment.
AB  - Novalis Tx ExacTrac X-ray system has the 6D adjustment ability for patient setup.
      Limited studies exist about the setup uncertainty with ExacTrac X-ray system for
      IMRT prostate treatment with fiducial markers implanted. The purpose of this
      study is to investigate the marker-based prostate IMRT treatment setup
      uncertainty using ExacTrac 6D IGRT ability for patient setup. Forty-three
      patients with prostate cancers and markers implanted have been treated on the
      Novalis Tx machine. The ExacTrac X-ray system has been used for the patient
      pretreatment setup and intratreatment verification. In total, the shifts data for
      1261 fractions and 3504 correction times (the numbers of X-ray images were taken
      from tube 1 and tube 2) have been analyzed. The setup uncertainty has been
      separated into uncertainties in 6D. Marker matching uncertainty was also
      analyzed. Correction frequency probability density function was plotted, and the
      radiation dose for imaging was calculated. The minimum, average, and maximum
      translation shifts were: -5.12 +/- 3.89 mm, 0.20 +/- 2.21 mm, and 6.07 +/- 4.44
      mm, respectively, in the lateral direction; -6.80 +/- 3.21 mm, -1.09 +/- 2.21 mm,
      and 3.12 +/- 2.62 mm, respectively, in the longitudinal direction; and -7.33 +/-
      3.46 mm, -0.93 +/- 2.70 mm, and 5.93 +/- 4.85mm, respectively, in the vertical
      direction. The minimum, average, and maximum rotation shifts were: -1.23 degrees 
      +/- 1.95 degrees , 0.25 degrees  +/- 1.30 degrees , and 2.38 degrees  +/- 2.91
      degrees , respectively, along lateral direction; -0.67 degrees  +/- 0.91 degrees
      , 0.10 degrees  +/- 0.61 degrees , and 1.51 degrees  +/- 2.04 degrees ,
      respectively, along longitudinal direction; and -0.75 degrees  +/- 1.01 degrees ,
      0.02 degrees  +/- 0.50 degrees , and 0.82 degrees  +/- 1.13 degrees ,
      respectively, along vertical direction. On average, each patient had three
      correction times during one fraction treatment. The radiation dose is about 3 mSv
      per fraction. With the ExacTrac 6D X-ray system, the prostate IMRT treatment with
      marker implanted can achieve less than 2 mm setup uncertainty in translations,
      and less than 0.25 degrees  in rotations as overall interfraction mean error. The
      imaging dose is less than kV (CBCT) for setup verification.

PMID- 22584177
TI  - Total body irradiation dose optimization based on radiological depth.
AB  - We have previously demonstrated the use of Eclipse fluence optimization to define
      aperture sizes for a novel aperture modulated translating bed total body
      irradiation (TBI) technique. The purposes of the present study were to identify,
      characterize, and correct for sources of error inherent in our previous fluence
      optimization technique, and to develop a clinically viable fluence optimization
      module for the translating bed TBI technique. Aperture modulated TBI is delivered
      by translating the patient at constant speed on a custom bed under a modulated
      radiation beam. The patient is then turned from supine to prone and the process
      repeated, resulting in an AP-PA treatment. Radiological depths were calculated
      along divergent ray lines through individual CT slices of a RANDO phantom. Beam
      apertures, defined using a dynamic multileaf collimator (DMLC), were generated
      using calculated radiological depths and calibration factors that relate fluence
      to aperture size in a dynamic environment. These apertures were defined every 9
      mm along the phantom superior-inferior axis. The calculated beam apertures were
      further modified to account for scatter within the patient. For dose calculation
      purposes the individual MLC files were imported into Eclipse. For treatment
      delivery, dynamic MLC files for both AP and PA beams were generated and delivered
      dynamically. Dose homogeneity in the head and neck region of the RANDO phantom
      was within +/- 4% of the prescribed dose with this novel technique compared to 
      5% to +7% with our previous aperture modulated technique based on Eclipse fluence
      optimization. Fluence optimization and beam aperture calculation using the new
      technique offers a ten-fold reduction in planning time and significantly reduces
      the likelihood of user error during the planning process. In conclusion, a
      clinically viable aperture modulated translating bed TBI technique that employs
      dynamically shaped MLC-defined beam apertures based on radiological depth
      calculations, has been developed.

PMID- 22584178
TI  - Accumulating daily-varied dose distributions of prostate radiation therapy with
      soft-tissue-based kV CT guidance.
AB  - Even with daily image guidance based on soft tissue registration, deviations of
      fractional doses can be quite large due to changes in patient anatomy. It is of
      interest to ascertain the cumulative effect of these deviations on the total
      delivered dose. Daily kV CT data acquired using an in-room CT for five prostate
      cancer patients were analyzed. Each daily CT was deformably registered to the
      planning CT using an in-house tool. The resulting deformation field was used to
      map the delivered daily dose onto the planning CT, then summed to obtain the
      cumulative (total delivered) dose to the patient. The delivered cumulative values
      of prostate D100 on average were only 2.9% less than their planned values, while
      the PTV D95 were 3.6% less. The delivered rectum and bladder V70s can be twice
      what was planned. The less than 3% difference between delivered and planned
      prostate coverage indicates that the PTV margin of 5 mm was sufficient with the
      soft-tissue-based kV CT guidance for the cases studied.

PMID- 22584179
TI  - Editorial: The commoditization of medical physics.

PMID- 22584180
TI  - Understanding the inflammatory  process in wound healing.
AB  - The basic elements of wound healing can be described using three sequential and
      overlapping phases: inflammation, proliferation and regeneration. These phases
      represent a highly organized, tightly regulated and complex sequence of events
      that are dependent on an exquisite balance between various cell types and
      mediators. Inflammation is a prerequisite to healing; however, chronic wounds in
      particular exhibit a prolonged inflammatory response, thus providing an ideal
      environment for bacterial infiltration and proliferation. Considering that
      approximately 70% of all wounds are chronic, with the majority of wound care
      being delivered in the community, this paper aims to support nurses in their
      understanding of inflammation in order to enhance clinical practice.

PMID- 22584181
TI  - Hand hygiene improvement in the community: a systems approach.
AB  - Hand hygiene compliance, which is influenced in part by human behaviour, is
      central to infection prevention in all care settings. This article focuses
      specifically on the importance of a multimodal strategy for continued hand
      hygiene improvement, and its relevance to community nursing. Additionally, the
      article addresses the challenges and opportunities of infection prevention and
      control in a community context, and highlights current national and international
      guidelines that offer a framework and set of principles for implementation and
      sustainability with a specific focus on the multimodal strategy associated with
      the WHO Guidelines on Hand Hygiene in Health Care (2009). The authors conclude
      with some considerations for community nurses when addressing translation of
      these principles into their everyday working context.

PMID- 22584182
TI  - Negative pressure wound therapy:  a study on patient perspectives.
AB  - AIM: to explore patients' lived experience of using negative pressure wound
      therapy (NPWT). METHOD: A phenomenological approach based on Heideggerian
      philosophy was undertaken. The study population consisted of 6 participants who
      had used NPWT for a minimum of 4 weeks. Semi-structured interviews were
      transcribed verbatim and investigated for themes using interpretative
      phenomenological analysis. RESULTS: Three superordinate themes were identified:
      altered sense of self, new culture of technology and leading a restricted life.
      Themes associated with an altered sense of self and leading a restricted life
      were in keeping with other wound care studies. Identification of barriers such as
      managing technical difficulties, practicalities of daily living, and improved
      understanding of NPWT for both patient and practitioner, can foster hope and
      reduce anxiety. CONCLUSIONS: Recommendations include holistic assessment of
      patient suitability for NPWT, education for patients and health professionals on
      NPWT, use of lighter, quieter devices, and the inclusion of a technology domain
      in future health-related quality of life studies on NPWT.

PMID- 22584183
TI  - Evaluation of a superabsorbent  dressing in a primary care organization.
AB  - This 40-patient evaluation of superabsorbent dressing DryMax Extra (Aspen
      Medical) was conducted within a large UK primary care organization adhering to an
      agreed evaluation protocol as approved by clinical governance. Exudate management
      and key performance requirements of absorbent dressings are considered with an
      analysis made of the clinical data relating to DryMax Extra. Clinical expectation
      of the product was rated and met in 38 of 40 cases, relating to ease of use,
      patient comfort, exudate management, maceration prevention, wear time and visual
      improvement of the wound bed. Additionally, evaluation findings resulted in a
      recommendation for formulary listing in 34 cases. Consequently, the authors
      recommend that there is a need for a large comparative study of the clinical and
      financial outcomes of superabsorbent dressings.

PMID- 22584184
TI  - Effective patient outcomes using  a gelling fibre dressing.
AB  - Exudate has an important function within the process of wound healing; however,
      maintaining the wound bed at the optimum moisture level is a key factor in the
      wound's progression (Moore, 2005). A patient's experience of living with a wound
      is often tarnished when leakage caused by the fluid discharged is unmanageable,
      which can subsequently have a negative effect on daily living and quality of life
      (Edwards, 2003). Such wounds can cause substantial pain, suffering, loss of self
      esteem, family distress, and a considerable financial cost to the NHS (Dowsett,
      2011). It is estimated that 2-3% of the local healthcare budget will be spent on
      chronic wound management (Posnett et al, 2009). This article will present three
      case studies demonstrating the effective use of a gelling fibre dressing
      (Durafiber, Smith & Nephew) used on different wound aetiologies, including the
      clinical benefits and patient outcomes.

PMID- 22584185
TI  - Interview: Jeanette Milne.

PMID- 22584186
TI  - Achieving your very best.

PMID- 22584188
TI  - Skin tears: achieving positive  clinical and financial outcomes.
AB  - Skin tears are one of the most common wounds found among frail, older
      individuals, and are considered to be largely preventable. Skin tears occur
      frequently in those with fragile skin, in neonates and the elderly; particularly
      those with comorbidities affecting their balance, e.g. postural hypotension,
      motor neurone disease, diabetes and cerebral vascular accident (CVA). Those
      taking oral medications including steroids and anticoagulants are also at risk of
      developing skin tears. The increase in the population of older people is likely
      to produce a concurrent rise in the number of skin tears. Health professionals
      and health care assistants have a significant role to play in skin tear
      prevention, assessment and management.

PMID- 22584189
TI  - What every physician should know about rapid diagnosis of Mycobacterium
      tuberculosis infection in children using interferon-gamma release assays.

PMID- 22584191
TI  - Epidemiology of atopic dermatitis: a review.
AB  - Atopic dermatitis (AD) is a common skin condition with significant associated
      social and financial burden. AD affects adults and children with worldwide
      prevalence rates of 1-20%. International study of epidemiology and geographic
      variability in prevalence of AD has been conducted in three phases with 1,000,000
      subjects in the third phase study. Prevalence continues to vary and has changed
      in different regions of the world. Nigeria, the United Kingdom and New Zealand
      had been areas of the highest prevalence; Latin America has emerged as a region
      of relatively high prevalence in follow up data. The prevalence of AD seems to
      have reached a plateau around 20% in countries with the highest prevalence,
      suggesting that AD may not be on a continued rise but that a finite number of
      individuals may be susceptible to the condition. Risk factors associated with
      increased prevalence include higher socioeconomic status, higher level of family
      education, smaller family size and urban environment. Research indicates that
      food allergy and atopic sensitization to environmental allergens may not be
      directly causal of the condition and that a non-atopic form of the condition
      exists. ~60% of patients will experience remission. The number of patients who
      will progress through the atopic march to develop asthma and allergic rhinitis
      depends on the underlying features of their condition.

PMID- 22584190
TI  - Rapid diagnosis of Mycobacterium tuberculosis infection in children using
      interferon-gamma release assays (IGRAs).
AB  - Diagnosis of tuberculosis (TB) in children by the tuberculin skin test (TST)
      poses a diagnostic challenge for physicians due to its low specificity and cross
      reactivity with nontuberculous mycobacteria and bacille Calmette-Guerin (BCG).
      Although interferon-gamma release assays (IGRAs) have been shown as novel TST
      alternatives for diagnosis of latent TB infection (LTBI) in adults, their
      effectiveness is less clear in children. The present study examined QuantiFERON
      TB Gold (QFT-G) responses and IFN-gamma production capacity of TST-positive
      children, younger children <=5 years. A total of 517 children of whom 434 were
      TST positive ranging in age from 1 month to 18 years were evaluated by the QFT-G.
      Of the 517 children, 434 (84%) were TST positive, 25 (5.8%) of whom were found to
      be QFT-G positive and 25 (5.4%) with an indeterminate response. Of the 517
      children, 355 (68.7%) were previously BCG immunized and 310/355 (87.3%) were TST
      positive including 18/27 (66.7%) QFT-positive children. Adequate IFN-gamma
      production by purified TB peptides or mitogen was observed in 92.8% of children,
      29.6% of whom were <5 years. This study shows that the QFT-G assay is useful for
      diagnosis of LTBI. The finding of 5.8% positive QFT-G in 434 TST-positive
      children underscores the superior specificity of the QFT-G than the TST and its
      greater cost effectiveness in preventing unnecessary and potentially toxic
      treatment in children. The study suggests that the majority of positive TST in
      children represent false-positive reactions and supports the use of IGRAs for
      diagnosis of LTBI in children, including those <5 years of age.

PMID- 22584192
TI  - Current options for prophylactic treatment of hereditary angioedema in the United
      States: patient-based considerations.
AB  - Hereditary angioedema (HAE) results from mutations in the C1-esterase inhibitor
      (C1 INH) gene that decrease production of C1 INH or render it dysfunctional. HAE
      is characterized by recurrent, unpredictable, bradykinin-mediated edema of the
      extremities, face, genitalia, trunk, gastrointestinal tract, or upper airway.
      Attacks causing laryngeal edema can be fatal. Patients with HAE need medications
      for acute attacks; some also require prophylaxis. Management requires
      consideration of the patient's disease burden and effect on the patient's quality
      of life. This review examines an individualized approach to identifying HAE
      patients who may benefit from prophylaxis. A literature search was performed for
      HAE and prophylaxis. HAE guidelines, case reports, safety studies, and
      randomized, controlled clinical prophylaxis trials were selected. Authors
      provided cases demonstrating individualized prophylaxis. U.S. Food and Drug
      Administration-approved options for prophylaxis of HAE include attenuated
      androgens and nanofiltered C1 INH (C1 INH-nf). In other countries, pasteurized C1
      INH and purified C1 INH are also available. Alternative therapies include fresh
      frozen plasma for preprocedural prophylaxis and antifibrinolytics for long-term
      prophylaxis. Attenuated androgens reduce attack frequency in many patients.
      Adverse effects include weight gain, virilization, increased hair growth,
      hypercholesterolemia, depression, and liver adenomas. C1 INH-nf reduces frequency
      of attacks and is well tolerated. Each patient with HAE has unique needs, based
      on the nature and frequency of past attacks, proximity to a medical center,
      occupation, and the patient's wishes. These factors should be used to create a
      patient-centered approach to management of HAE.

PMID- 22584193
TI  - Discrepancies between guidelines and international practice in treatment of
      hereditary angioedema.
AB  - Hereditary angioedema (HAE) is an autosomal dominant disorder characterized by
      decreased expression or loss of function of C1 esterase inhibitor (C1-INH). In
      2010, international guidelines were published regarding the management of both
      acute HAE attacks and prophylactic treatment. Additionally, several clinical
      trials for HAE therapies were published in 2010. The purpose of this study was to
      assess the adherence of internationally based physicians to the current evidence
      based studies and the 2010 International Consensus Algorithm. Internationally
      based physician members of the World Allergy Organization were surveyed regarding
      their diagnosis and management of patients with HAE. Only physicians who treat
      HAE patients were included in the analyses. Of the 201 responding physicians, the
      most highly used therapies for acute HAE attacks were C1-INH (59%), fresh frozen
      plasma (FFP; 42%), and icatibant (32%). For their preferred long-term
      prophylactic therapy, 74% used attenuated androgens and 18% used
      antifibrinolytics. Physicians in Latin and South America, in particular, were
      less likely than their international counterparts to prescribe C1-INH and more
      likely to prescribe attenuated androgens and FFP, and European physicians were
      the most likely to prescribe icatibant. Over one-third of physicians described
      themselves as "unfamiliar" with emerging HAE therapies. Many international
      physicians neither follow current evidence-based studies nor adhere to the 2010
      International Consensus Algorithm for treating HAE. Further education of
      physicians, government authorities, and professional medical groups is necessary
      to enhance availability to therapies and appropriate use of them.

PMID- 22584194
TI  - Role of specific IgE and skin-prick testing in predicting food challenge results
      to baked egg.
AB  - Previous studies suggest that children with egg allergy may be able to tolerate
      baked egg. Reliable predictors of a successful baked egg challenge are not well
      established. We examined egg white-specific IgE levels, skin-prick test (SPT)
      results, and age as predictors of baked egg oral food challenge (OFC) outcomes.
      We conducted a retrospective chart review of children, aged 2-18 years, receiving
      an egg white-specific IgE level, SPT, and OFC to baked egg from 2008 to 2010.
      Fifty-two oral baked egg challenges were conducted. Of the 52 challenges, 83% (n
      = 43) passed and 17% (n = 9) failed, including 2 having anaphylaxis. Median SPT
      wheal size was 12 mm (range, 0-35 mm) for passed challenges and 17 mm (range, 10
      30 mm) for failed challenges (p = 0.091). The negative predictive value for
      passing the OFC was 100% (9 of 9) if SPT wheal size was <10 mm. Median egg white
      specific IgE was 2.02 kU/L (range, <0.35-13.00 kU/L) for passed challenges and
      1.52 kU/L (range, 0.51-6.10 kU/L) for failed challenges (p = 0.660). Receiver
      operating characteristic (ROC) curve analysis for SPT revealed an area under the
      curve (AUC) of 0.64. ROC curve analysis for egg white-specific IgE revealed an
      AUC of 0.63. There was no significant difference in age between patients who
      failed and those who passed (median = 8.8 years versus 7.0 years; p = 0.721).
      Based on our sample, SPT, egg white-specific IgE and age are not good predictors
      of passing a baked egg challenge. However, there was a trend for more
      predictability with SPT wheal size.

PMID- 22584195
TI  - Effect of cat and daycare exposures on the risk of asthma in children with atopic
      dermatitis.
AB  - Atopic dermatitis (AD) in young children is often followed by the development of
      asthma (atopic march). The role of environmental exposures is unclear in this
      high-risk population. We aimed to determine the predictive relationship between
      indoor allergen exposures, particularly pets, rodents, and cockroaches, to the
      development of asthma in a prospective pediatric cohort. Children with AD and a
      family history of allergy were followed prospectively with questionnaire
      ascertainment of environmental exposure to cats, dogs, cockroaches, rats, and
      mice. Asthma was diagnosed by study physicians based on caregiver reports of
      symptoms continually assessed over the course of the study period. Fifty-five of
      the 299 children developed asthma by the end of the study. Cat exposure had a
      strong and independent effect to reduce the risk of developing asthma across all
      analyses (odds ratio [OR], 0.16; 95% confidence interval [CI], 0.05-0.53). Dog,
      mouse, rat, and cockroach exposures did not significantly influence the
      development of asthma. Daycare exposure had the largest risk reduction for the
      development of asthma (OR, 0.08; 95% CI, 0.03-0.19). Maternal asthma (OR, 2.93;
      95% CI, 1.29-6.67), baseline body mass index (OR, 1.23; 95% CI, 1.08-1.42), and
      specific immunoglobulin E to house-dust mix at 3 years were each independent risk
      factors for the development of asthma. In children with AD, cat and daycare
      exposure may reduce the risk of developing early childhood asthma.

PMID- 22584196
TI  - Assessment of the association between atopic conditions and tympanostomy tube
      placement in children.
AB  - This study assesses the relationship between otitis media and atopic conditions
      in children by comparing the incidence of tympanostomy tube placement between
      children with and without atopic conditions: asthma, allergic rhinitis, and
      atopic dermatitis. Study subjects were a cohort of  323 healthy children who
      participated in a study of vaccine response. All episodes of tympanostomy tube
      placement and physician diagnoses of allergic rhinitis and atopic dermatitis were
      collected through comprehensive medical record review. Asthma status was
      ascertained through application  of established criteria. We compared incidence
      rates of tympanostomy tube placement between children with and without atopic
      conditions. We fitted data to a Poisson regression model to calculate relative
      risk ratios (RRs) and their corresponding 95% confidence intervals (95% CI).
      Three subjects  were excluded who did not have parental authorization for using
      records for research. Of the remaining 320 subjects, 170 (53%) were male
      subjects, 268 (94%) were white, 124 (39%) were asthmatic patients, and 20 (6%)
      had tympanostomy tube placement. Children with asthma before the index date  of
      tympanostomy tube placement were more likely to have tympanostomy tube placement
      compared with those without asthma (RR, 19.33; 95% CI, 11.41; 32.75; p < 0.001).
      We found a similar association between asthma ever (before or after index date)
      and the incidence of tympanostomy tube placement  (RR, 1.53; 95% CI, 0.93-2.53; p
      = 0.095). This was true for children with allergic rhinitis compared with those
      without allergic rhinitis (RR, 1.70; 95% CI, 1.01-2.86; p = 0.007). Atopic
      dermatitis was not associated with the incidence of tympanostomy tube placement.
      Asthma or  allergic rhinitis may be unrecognized risk factors for recurrent or
      persistent otitis media. However, given the small sample size of the study, a
      cohort study with a larger sample size is necessary.

PMID- 22584198
TI  - [Benefits of continuous subcutaneous insulin infusion in children with type 1
      diabetes mellitus].
AB  - BACKGROUND: The Diabetes Control and Complications Trial clearly demonstrated the
      benefits of blood glucose control, especially in children and adolescents, in the
      prevention of long-term complications of type 1 diabetes (T1D). This can be
      achieved with intensive insulin treatment with either multiple daily insulin
      injections (MDI) or continuous subcutaneous insulin infusion (CSII), also known
      as insulin pump. The aim of this study was to compare glycemic control of T1D
      children treated with either CSII or MDI. PATIENTS AND METHODS: Thirty-eight T1D
      children treated with CSII were compared to 38 children treated with MDI, matched
      for age, gender, and duration of diabetes. Collected data, including daily doses
      of insulin in IU/kg/d, HbA1c levels, body mass index expressed in standard
      deviation/age, number of severe hypoglycemia episodes and of admissions related
      to T1D expressed in events/patient/year, were retrospectively collected every 3
      months. RESULTS: There was no difference between the 2 groups at baseline. During
      the 3 years of follow-up, patients treated with CSII had lower daily doses of
      insulin (0.78 +/- 0.19 vs. 0.87 +/- 0.22 IU/kg/d, p<0.05), significantly lower
      levels of HbA1c (7.5 +/- 0.6 vs. 8.0 +/- 1.3 %, p<0.05), and a decreased number
      of admissions related to T1D (0.07 +/- 0.14 vs. 0.17 +/- 0.22
      events/patient/year, p<0.05) than children treated with MDI. In contrast, body
      mass index and number of severe hypoglycemic episodes did not differ between the
      two groups. No diabetic ketoacidosis episode was recorded in either group.
      CONCLUSION: The results from this study suggest that treatment with CSII provided
      better metabolic control than treatment with MDI, in spite of lower daily doses
      of insulin and without increasing acute complications, in children with T1D.

PMID- 22584197
TI  - Prolonged urticaria and fever in a toddler.
AB  - We describe a 14-month-old girl who initially presented with 8 days of fever,
      conjunctival injection, rash, and irritability, admitted with a presumptive
      diagnosis of Kawasaki disease. Further history revealed intermittent urticarial
      like rash since 3 months of age and pathological evaluation showed a perivascular
      infiltrate of neutrophils and lymphocytes. Here, we discuss the key points
      surrounding her diagnostic workup and our therapeutic approach.

PMID- 22584199
TI  - Nutcracker syndrome: Is it really a rare cause of hematuria? Comment on: Le
      syndrome casse-noisette (Nutcracker) : une cause rare d'hematurie. Arch Pediatr
      2011;18:1188-90.

PMID- 22584200
TI  - The latent classes of subclinical ADHD symptoms: convergences of multiple
      informant reports.
AB  - The purpose of the present study was to conduct latent class analysis on the
      Hyperactivity scale of the Strengths and Difficulties Questionnaire in order to
      identify distinct subgroups of subclinical ADHD in a multi-informant framework.
      We hypothesized a similar structure between teachers and parents, and differences
      in symptom severity across latent classes. Data was collected from a non-referred
      sample of children aged 8-13 years. We performed latent class analyses on parent
      (n = 383) and teacher (n = 391) ratings of the Hyperactivity scale items from
      both versions of the questionnaire. Those children who had ratings from both
      informants (n = 272) were included in the cross-informant analyses, in which the
      similar or equivalent classes across raters were determined. A three-class
      solution for parent report and a five-class solution for teacher report emerged
      in the subsample of boys. For girls, a three-class structure for parents and a
      four-class structure for teachers were optimal. Besides non-symptomatic groups,
      mild and severe combined classes, mild inattentive-impulsive classes, and among
      boys, a mild hyperactive-impulsive class was obtained. The cross-informant
      analyses demonstrated that quite similar subgroups were detached regardless of
      informant; however, the teacher classes were somewhat more elaborated. The
      results are in line with the previous latent class analytic studies, and support
      the combination of dimensional and categorical approaches. The importance of
      milder symptoms and sub-threshold ADHD categories are emphasized for the fields
      of neuropsychology, neuroscience, and education, as well as for diagnosis and
      personalized treatment.

PMID- 22584201
TI  - Microscopic observation drug susceptibility assay in the diagnosis of multidrug
      resistant tuberculosis.
AB  - BACKGROUND: Early detection of multidrug-resistant Mycobacterium tuberculosis
      (MDR-TB) is of primary importance for both patient management and infection
      control. Optimal methods for identifying MDR-TB in a timely and affordable manner
      in resource-limited settings are not yet available. OBJECTIVES: To evaluate the
      performance of a low-technology but rapid drug susceptibility testing method, the
      microscopic observation drug susceptibility assay (MODS), in the concurrent
      detection of M. tuberculosis and its susceptibility to isoniazid (INH) and
      rifampin (RMP) directly from sputum specimens. METHODS: A total of 115 smear
      positive TB patients admitted to Abbasia Chest Hospital, Cairo, Egypt, were
      simultaneously tested using MODS and the BACTEC MGIT 960 mycobacterial detection
      system for the detection of M. tuberculosis and the identification of MDR-TB
      samples. RESULTS: MODS detected 112 (97.4%) samples and BACTEC MGIT detected 115
      (100%). Of the 115 isolates tested for susceptibility to INH, RMP and MDR-TB,
      complete agreement between MODS and MGIT results was found among respectively
      92.9%, 95.5% and 97.3% of samples. The sensitivity, specificity, and positive and
      negative predictive values of MODS in the detection of MDR-TB were respectively
      95.3%, 98.6%, 97.6% and 97.1%. MODS results were obtained in a median of 8 days
      (range 5-21). CONCLUSION: MODS is an optimal alternative method for timely and
      affordable identification of MDR-TB in resource-limited settings.

PMID- 22584202
TI  - Effects of dietary mannan oligosaccharide on growth performance, gut morphology
      and stress tolerance of juvenile Pacific white shrimp, Litopenaeus vannamei.
AB  - An 8-week feeding trial was conducted to investigate the effects of dietary
      mannan oligosaccharide (MOS) on growth performance, gut morphology, and NH(3)
      stress tolerance of Pacific white shrimp Litopenaeus vannamei. Juvenile Pacific
      white shrimp (1080 individuals with initial weight of 2.52 +/- 0.01 g) were fed
      either control diet without MOS or one of five dietary MOS (1.0, 2.0, 4.0, 6.0
      and 8.0 g kg(-1)) diets. After the 8-week feeding trial, growth parameters,
      immune parameters, intestinal microvilli length and resistance against NH(3)
      stress were assessed. Weight gain (WG) and specific growth rate (SGR) were
      significantly higher (P < 0.05) in shrimp fed 2.0, 4.0, 6.0 and 8.0 g kg(-1) MOS
      supplemented diets than shrimp fed control diet. WG and SGR of shrimp fed 2.0 g
      kg(-1) MOS-supplemented diet was the highest (P < 0.05) in all experimental
      groups. Survival rate (SR) of shrimp was generally similar (P > 0.05) in all
      experimental groups. Compared with control group, TEM analysis revealed that 2.0,
      4.0, 6.0 and 8.0 g kg(-1) MOS supplementation could significantly increase (P <
      0.05) the intestinal microvilli length of shrimp at the ultrastructural level.
      After NH(3) stress for 24 h, SR of shrimp fed 2.0, 4.0, 6.0 and 8.0 g kg(-1) MOS
      supplemented diets was significantly higher (P < 0.05) than that of shrimp fed
      control diet. Phenoloxidase (PO) activity of 4.0 g kg(-1) MOS-supplemented group
      was significantly higher (P < 0.05) than that of control group under normal
      conditions and NH(3) stress. PO activity significantly decreased (P < 0.05) under
      NH(3) stress than under normal conditions. Superoxide dismutase (SOD) activity of
      4.0, 6.0 and 8.0 g kg(-1) MOS-supplemented groups was significantly higher (P <
      0.05) than that of control group under normal conditions. After NH(3) stress for
      24 h, SOD activity of all experimental groups also significantly decreased (P <
      0.05) compared to normal conditions. These results clearly indicated that dietary
      MOS could improve growth performance and increase the resistance against NH(3)
      stress in L. vannamei, and the 2.0-4.0 g kg(-1) MOS supplementation was suitable
      for L. vannamei.

PMID- 22584203
TI  - Insulin-like growth factor binding protein 7, a member of insulin-like growth
      factor signal pathway, involved in immune response of small abalone Haliotis
      diversicolor.
AB  - Insulin-like growth factor binding protein 7 (IGFBP7), the only member of the
      IGFBP superfamily that binds strongly to insulin, may have different functions
      from other IGFBPs. Unlike other IGFBPs, there is no knowledge available on
      aquatic invertebrate IGFBP7. In this study, a molluscan IGFBP7 gene, saIGFBP7,
      was cloned for the first time from the small abalone Haliotis diversicolor. Its
      full-length cDNA sequence is 1812 bp, with a 720 bp open reading frame encoding a
      protein of 239 aa. The molecular mass of the deduced protein is approximately
      25.37 kDa with an estimated pI of 5.00, and it shares highest 41% identity to
      IGFBP7 of Amblyomma americanum. Analysis of conserved domains revealed the
      presence of an IGFBP N-terminal domain (IB), a kazal-type serine proteinase
      inhibitor domain (KI), and an immunoglobulin-like C2 domain (IgC2) in saIGFBP7.
      Furthermore, the 12 cysteine residues and the signature amino acid motif
      'xCGCCxxC' which are characterized by the amino terminus region of the IGFBP
      superfamily are all presented in saIGFBP7. Quantitative real-time PCR and western
      blot were employed to investigate the tissue distribution of saIGFBP7, and its
      expression under bacterial challenge. The saIGFBP7 mRNA and protein could be
      detected in all examined tissues, with the highest expression level in hemocytes,
      higher expression level in gills, and was up-regulated in hemocytes and gills
      after bacterial injection. In addition, saIGFBP7 mRNA transcripts were observed
      in a subset of the branchial epithelium and the nucleus of hemocytes using the in
      situ hybridization method. Interestingly, saIGFBP7 was detected mainly in the
      goblet-like cell of the branchial epithelium by immunohistochemistry. These
      results suggested that saIGFBP7 was likely to be involved in a function
      associated with pathogenic infection and may play an important role in the adult
      abalone immune system.

PMID- 22584209
TI  - Are proprioceptive-induced reflex seizures epileptically-enhanced stretch reflex
      manifestations?
AB  - In reflex seizures induced by proprioceptive stimuli, the activated network may
      be identified as a single anatomo-functional circuit; the sensory-motor network.
      These seizures may be considered as epileptically-enhanced stretch reflexes.
      Proprioceptive reflex epilepsies are a good example of the so-called "system
      epilepsies". We present three cases discussing the clinical features of such
      epilepsies. [Published with videosequences].

PMID- 22584212
TI  - Joint annual meeting of the Swiss Society of Pneumology, Swiss Society of
      Pediatric Pneumology, Swiss Society for Thoracic Surgery, Swiss Underwater and
      Hyperbaric Medical Society, Crans-Montana, April 25-27, 2012.

PMID- 22584211
TI  - Pleural effusion in lung cancer: more questions than answers.
AB  - Lung cancer remains the most common fatal malignancy, despite more aggressive
      therapies. Few patients will survive 5 years, as up to 80% of the patients will
      present with advanced-stage disease at diagnosis. Chemotherapy offers little
      benefit in terms of median survival and disease-free survival in patients with
      advanced-stage non-small-cell lung carcinoma (NSCLC). In the last decade, the
      development of new targeted therapies based on the better understanding of
      different paths of carcinogenesis has given new hope to both physicians and
      patients. Metastatic pleural effusion from lung cancer has a particularly poor
      prognosis, and in NSCLC it is actually reclassified as stage IV disease. A
      possible explanation of this observation is differences in the genomics between
      primary tumors and metastasis, leading to possible different therapeutic
      approaches with novel molecular therapies in this patient population. The current
      review aims to summarize the actual situation of research in pleural disease due
      to lung carcinoma in relation to novel targeted therapies tested in this patient
      population.

PMID- 22584210
TI  - Autoinhibition of ETV6 (TEL) DNA binding: appended helices sterically block the
      ETS domain.
AB  - ETV6 (or TEL), a transcriptional repressor belonging to the ETS family, is
      frequently involved in chromosomal translocations linked with human cancers. It
      displays a DNA-binding mode distinct from other ETS proteins due to the presence
      of a self-associating PNT domain. In this study, we used NMR spectroscopy to
      dissect the structural and dynamic bases for the autoinhibition of ETV6 DNA
      binding by sequences C-terminal to its ETS domain. The C-terminal inhibitory
      domain (CID) contains two helices, H4 and H5, which sterically block the DNA
      binding interface of the ETS domain. Importantly, these appended helices are only
      marginally stable as revealed by amide hydrogen exchange and (15)N relaxation
      measurements. The CID is thus poised to undergo a facile conformational change as
      required for DNA binding. The CID also dampens millisecond timescale motions of
      the ETS domain hypothesized to be critical for the recognition of specific ETS
      target sequences. This work illustrates the use of appended sequences on
      conserved structural domains to generate biological diversity and complements
      previous studies of the allosteric mechanism of ETS1 autoinhibition to reveal
      both common and divergent features underlying the regulation of DNA binding by
      ETS transcription factors.

PMID- 22584214
TI  - Vaginal bleeding in early pregnancy and associations with physical, psychological
      and environmental factors among Chinese women: from the C-ABC cohort study.
AB  - OBJECTIVES: To examine sociodemographic, physical, psychological and
      environmental factors that may be associated with vaginal bleeding (VB) in the
      first trimester. METHODS: A questionnaire survey was conducted on 14,752 women by
      trained doctors, when pregnant women came for the first antenatal examination,
      including sociodemographic characteristics, prior adverse pregnancy outcomes,
      diseases history, life event stress, adverse environmental exposure and detailed
      information on VB. RESULTS: VB occurred among 3,466 pregnant women, the
      prevalence of VB was 23.4% in the first trimester, 35.9% of whom did not see a
      doctor, 59.7% of whom went to clinic and only 4.4% of whom were hospitalized for
      VB. Multinomial logistic regression demonstrated that the following risk factors
      may be associated with VB with seeing a doctor: age >25 years, education greater
      than primary school, urban residence, prior spontaneous abortion, prior surgical
      abortion and previous stillbirth, having gynecological inflammation, chest X-ray
      examination and life events stress score >2 during the periconception period. Age
      >25 years, urban residence, prior surgical abortion, having gynecological
      inflammation and a life event stress score >2 during the periconception period
      may be related to VB without seeing a doctor. CONCLUSIONS: This epidemiologic
      study provided more information on predictors of VB: physical, psychological and
      adverse environmental exposure were all associated with VB in the first
      trimester.

PMID- 22584215
TI  - Aggressiveness features and outcomes of true interval cancers:  comparison
      between screen-detected and symptom-detected cancers.
AB  - The question of whether screen detection confers an additional survival benefit
      in breast cancer is unclear and subject to several biases. Our aim was to examine
      the role of the diagnostic method (screen-detected, symptom-detected, and true
      interval cancers) and the clinical-pathological features in relapse-free survival
      and overall survival in breast cancer patients. We included 228 invasive breast
      cancers diagnosed in Barcelona from 1996 to 2008 among women aged 50-69 years.
      Ninety-seven patients were screen detected within the screening, 34 truly arose
      between 2-year screening mammograms (true interval cancers), and 97 were symptom
      detected outside the screening. The clinical-pathological features at diagnosis
      were compared. The overall and disease-free survival probabilities were computed
      using the Kaplan-Meier method. Cox proportional hazard models were applied, with
      adjustment by clinical-pathological variables. At diagnosis, symptom-detected and
      true interval cancers were in more advanced stages and were less differentiated.
      The highest proportion of triple-negative cancers was detected among true
      interval cancers (P=0.002). At 5 years of follow-up, the disease-free survival
      rates for screen-detected, true interval, and symptom-detected cancers were 87.5%
      (95% confidence interval, 80.5-95.2%), 64.1% (46.4-88.5%), and 79.4% (71.0
      88.8%), respectively, and the overall survival rates were 94.5% (89.3-99.9%),
      65.5% (47.1-91.2%), and 85.6% (78.3-93.6%), respectively. True interval cancers
      had the highest hazard ratio for relapse prediction (1.89; 0.67-5.31) and a
      hazard ratio of death of 5.55 (1.61-19.15) after adjustment for tumor-node
      metastasis stage and phenotype. Clinically detected tumors, especially true
      interval cancers, more frequently showed biological features related to worse
      prognosis and were associated with poorer survival even after adjustment for
      clinical-pathological characteristics.

PMID- 22584216
TI  - Dietary glycemic index, glycemic load, and the risk of endometrial cancer:  a
      case-control study and meta-analysis.
AB  - Carbohydrates and the dietary glycemic index (GI) influence insulin secretion and
      insulin-like growth factors, and may exert relevant effects on obesity and
      diabetes, both of which are important risk factors for endometrial cancer. We
      studied the association between dietary GI and glycemic load (GL) and endometrial
      cancer using data from an Italian case-control study. This included 454 women
      with histologically confirmed endometrial cancer and 908 controls admitted to the
      same hospitals for acute, non-neoplastic conditions. Multivariate odds ratios
      were obtained after allowance for major potential confounding factors, including
      noncarbohydrate energy intake. We updated a meta-analysis on this issue,
      including a recent US cohort study, which contributed about a quarter of all
      cases, besides our case-control study. In the case-control study, the odds ratios
      of endometrial cancer for the highest versus the lowest quintile were 1.03 [95%
      confidence interval (CI): 0.67-1.58] for GI and 1.01 (95% CI: 0.64-1.61) for GL.
      No heterogeneity was found across the strata of diabetes and other selected
      covariates. The summary risk estimate of endometrial cancer for the highest
      versus the lowest GI level, obtained from the meta-analysis, was 1.09 (95% CI:
      0.92-1.29). The corresponding risk estimate for GL was 1.19 (95% CI: 1.06-1.34).
      The case-control study showed no association between dietary GI and GL and the
      risk of endometrial cancer overall and in the strata of relevant covariates,
      whereas the meta-analysis supported an increased risk for high GL, but not GI.

PMID- 22584217
TI  - Prospective evaluation of subjects with chronic asymptomatic pancreatic
      hyperenzymemia.
AB  - OBJECTIVES: Chronic asymptomatic pancreatic hyperenzymemia (CAPH) has been
      described since 1996 as a benign disease. Recent studies described pathological
      findings at magnetic resonance cholangiopancreatography with secretin stimulation
      (s-MRCP) in more than half of the CAPH subjects. The aim of this study was to
      investigate the frequency and clinical relevance of s-MRCP findings in patients
      with CAPH. METHODS: Subjects prospectively enrolled from January 2005 to December
      2010 underwent s-MRCP and biochemical tests routinely performed. RESULTS: Data
      relative to 160 subjects (94 males, 66 females, age 49.6+/-13.6 years) were
      analyzed. In all, 51 (32%) subjects had hyperamylasemia, 9 (6%) hyperlipasemia,
      and 100 (62%) an increase in both enzyme levels. The time between the first
      increased dosage of serum pancreatic enzymes and our observation was 3.3+/-3.9
      years (range: 1-15). Familial pancreatic hyperenzymemia was observed in 26 out of
      133 subjects (19.5%). Anatomic abnormalities of the pancreatic duct system at s
      MRCP were found in 24 out of 160 subjects (15%). Pathological MRCP findings were
      present in 44 subjects (27.5%) before and in 80 subjects (50%) after secretin
      administration (P<0.0001). Five subjects (3.1%) underwent surgery, 3 for
      pancreatic endocrine tumor, 1 for pancreatic adenocarcinoma, and 1 for
      intraductal papillary-mucinous neoplasia (IPMN) involving the main pancreatic
      duct, and 18 patients (11.3%) needed a follow-up (17 for IPMN and 1 for endocrine
      tumor). CONCLUSIONS: Alterations of the pancreatic duct system at s-MRCP in
      subjects with CAPH can be observed in 50% of the subjects and are clinically
      relevant in 14.4% of cases.

PMID- 22584218
TI  - The incidence and risk of celiac disease in a healthy US adult population.
AB  - OBJECTIVES: Celiac disease (CD) is an increasingly common disease that may affect
      as many as 1% of the North American population. Recent population-based data
      suggest a substantial increase in the prevalence of CD over the last several
      decades. Several factors are hypothesized as possible disease triggers including
      intercurrent illnesses, such as gastroenteritis, surgeries, and trauma. We used
      the active duty US military, a unique healthy worker population with essentially
      complete medical diagnostic coding, as an opportunity to describe trends in CD
      and deployment-related risk factors. METHODS: Using electronic medical encounter
      data (1999-2008) on active duty US military (over 13.7 million person-years), a
      matched, nested case-control study describing the epidemiology and risk
      determinants of CD (based on >=2 ICD-9 medical encounters) was conducted.
      Incidence and duration of CD-related medical care were estimated, and conditional
      logistic regression was utilized to evaluate CD risk following infectious
      gastroenteritis (IGE) occurring within 3 years before CD diagnosis while
      controlling for other risk factors. RESULTS: A total of 455 incident cases of CD
      were identified and age, gender, and time matched to 1,820 controls. The
      incidence of CD increased five-fold from 1.3 per 100,000 in 1999 to 6.5 per
      100,000 in 2008, with the highest rates of increase among those over 34 years of
      age (average annual increase of 0.8 cases per 100,000). A total of 172 IGE
      episodes, predominately of "viral etiology" (60.5%), were documented. In
      multivariate models, a significant association between IGE and CD was found (Odds
      ratio (OR): 2.06, 95% confidence interval (CI) 1.43, 2.97). Risk generally
      increased with temporal proximity to, and non-viral etiology of, exposure. Other
      notable risk factors for CD in multivariate models were Caucasian race (OR: 3.1,
      P<0.001), non-Army service (OR: 1.5, P=0.001), and greater than a high-school
      education (OR: 1.3, P=0.05). CONCLUSIONS: Incidence of CD diagnosis in the US
      military is increasing, particularly among those in the fourth and fifth decades
      of life and appears higher than other population-based estimates. An association
      between antecedent IGE and risk of CD was noted, but the potential for exposure
      misclassification cannot be ruled out and further study is needed to link
      pathogen-specific exposure to incident CD anti-gluten antibody development or
      symptom onset.

PMID- 22584219
TI  - Ligand bias at metabotropic glutamate 1a receptors: molecular determinants that
      distinguish beta-arrestin-mediated from G protein-mediated signaling.
AB  - The metabotropic glutamate 1a (mGlu1a) receptor is a G protein-coupled receptor
      linked with phosphoinositide (PI) hydrolysis and with beta-arrestin-1-mediated
      sustained extracellular signal-regulated kinase (ERK) phosphorylation and
      cytoprotective signaling. Previously, we reported the existence of ligand bias at
      this receptor, inasmuch as glutamate induced both effects, whereas quisqualate
      induced only PI hydrolysis. In the current study, we showed that mGlu1 receptor
      agonists such as glutamate, aspartate, and l-cysteate were unbiased and activated
      both signaling pathways, whereas quisqualate and (S)-3,5-dihydroxyphenylglycine
      stimulated only PI hydrolysis. Competitive antagonists inhibited only PI
      hydrolysis and not the beta-arrestin-dependent pathway, whereas a noncompetitive
      mGlu1 receptor antagonist blocked both pathways. Mutational analysis of the
      ligand binding domain of the mGlu1a receptor revealed that Thr188 residues were
      essential for PI hydrolysis but not for protective signaling, whereas Arg323 and
      Lys409 residues were required for beta-arrestin-1-mediated sustained ERK
      phosphorylation and cytoprotective signaling but not for PI hydrolysis.
      Therefore, the mechanism of ligand bias appears to involve different modes of
      agonist interactions with the receptor ligand binding domain. Although some
      mGlu1a receptor agonists are biased toward PI hydrolysis, we identified two
      endogenous compounds, glutaric acid and succinic acid, as new mGlu1 receptor
      agonists that are fully biased toward beta-arrestin-mediated protective
      signaling. Pharmacological studies indicated that, in producing the two effects,
      glutamate interacted in two distinct ways with mGlu1 receptors, inasmuch as
      competitive mGlu1 receptor antagonists that blocked PI hydrolysis did not inhibit
      cytoprotective signaling. Quisqualate, which is biased toward PI hydrolysis,
      failed to inhibit glutamate-induced protection, and glutaric acid, which is
      biased toward protection, did not interfere with glutamate-induced PI hydrolysis.
      Taken together, these data indicate that ligand bias at mGlu1 receptors is
      attributable to different modes of receptor-glutamate interactions, which are
      differentially coupled to PI hydrolysis and beta-arrestin-mediated cytoprotective
      signaling, and they reveal the existence of new endogenous agonists acting at
      mGlu1 receptors.

PMID- 22584220
TI  - Formation of the thiol conjugates and active metabolite of clopidogrel by human
      liver microsomes.
AB  - We reported previously the formation of a glutathionyl conjugate of the active
      metabolite (AM) of clopidogrel and the covalent modification of a cysteinyl
      residue of human cytochrome P450 2B6 in a reconstituted system (Mol Pharmacol
      80:839-847, 2011). In this work, we extended our studies of the metabolism of
      clopidogrel to human liver microsomes in the presence of four reductants, namely,
      GSH, l-Cys, N-acetyl-l-cysteine (NAC), and ascorbic acid. Our results
      demonstrated that formation of the AM was greatly affected by the reductant used
      and the relative amounts of the AM formed were increased in the following order:
      NAC (17%) < l-Cys (53%) < ascorbic acid (61%) < GSH (100%). AM-thiol conjugates
      were observed in the presence of NAC, l-Cys, and GSH. In the case of GSH, the
      formation of both the AM and the glutathionyl conjugate was dependent on the GSH
      concentrations, with similar K(m) values of ~0.5 mM, which indicates that
      formation of the thiol conjugates constitutes an integral part of the
      bioactivation processes for clopidogrel. It was observed that the AM was slowly
      converted to the thiol conjugate, with a half-life of ~10 h. Addition of
      dithiothreitol to the reaction mixture reversed the conversion, which resulted in
      a decrease in AM-thiol conjugate levels and a concomitant increase in AM levels,
      whereas addition of NAC led to the formation of AM-NAC and a concomitant decrease
      in AM-GSH levels. These results not only confirm that the AM is formed through
      oxidative opening of the thiolactone ring but also suggest the existence of an
      equilibrium between the AM, the thiol conjugates, and the reductants. These
      factors may affect the effective concentrations of the AM in vivo.

PMID- 22584222
TI  - Pentadecatungstotrivanadodiphosphoric heteropoly acid with Dawson structure:
      Synthesis, conductivity and conductive mechanism.
AB  - A general strategy in terms of degradating and ion-exchange synthesis was used to
      design pentadecatungstotrivanadodiphosphoric heteropoly acid
      H(9)P(2)W(15)V(3)O(62).28H(2)O with Dawson structure and excellent conductivity.
      The product was characterized by ICP-MS, IR, UV, XRD, (31)P NMR, TG-DTA and
      electrochemical impedance spectroscopy (EIS). The results indicate that
      H(9)P(2)W(15)V(3)O(62).28H(2)O possesses the Dawson structure. EIS measurements
      show a high conductivity (3.64 * 10(-2) S cm(-1) at 26  degrees C and 75%
      relative humidity), with an activation energy of 31.34 kJ mol(-1) for proton
      conduction. Its mechanism for proton conduction is the Vehicle mechanism.

PMID- 22584221
TI  - Telomere and microtubule targeting in treatment-sensitive and treatment-resistant
      human prostate cancer cells.
AB  - Modulating telomere dynamics may be a useful strategy for targeting prostate
      cancer cells, because they generally have short telomeres. Because a plateau has
      been reached in the development of taxane-based treatments for prostate cancer,
      this study was undertaken to evaluate the relative efficacy of targeting
      telomeres and microtubules in taxane-sensitive, taxane-resistant, androgen
      sensitive, and androgen-insensitive prostate cancer cells. Paclitaxel- and
      docetaxel-resistant DU145 cells were developed and their underlying adaptive
      responses were evaluated. Telomere dynamics and the effects of targeting
      telomeres with sodium meta-arsenite (KML001) (an agent undergoing early clinical
      trials), including combinations with paclitaxel and docetaxel, were evaluated in
      parental and drug-resistant cells. The studies were extended to androgen
      sensitive LNCaP cells and androgen-insensitive LNCaP/C81 cells. Both P
      glycoprotein (Pgp)-dependent and non-Pgp-dependent mechanisms of resistance were
      recruited within the same population of DU145 cells with selection for drug
      resistance. Wild-type DU145 cells have a small side population (SP) (0.4-1.2%).
      The SP fraction increased with increasing drug resistance, which was correlated
      with enhanced expression of Pgp but not breast cancer resistance protein.
      Telomere dynamics remained unchanged in taxane-resistant cells, which retained
      sensitivity to KML001. Furthermore, KML001 targeted SP and non-SP fractions,
      inducing DNA damage signaling in both fractions. KML001 induced telomere erosion,
      decreased telomerase gene expression, and was highly synergistic with the taxanes
      in wild-type and drug-resistant DU145 cells. This synergism extended to androgen
      sensitive and androgen-insensitive LNCaP cells under basal and androgen-deprived
      conditions. These studies demonstrate that KML001 plus docetaxel and KML001 plus
      paclitaxel represent highly synergistic drug combinations that should be explored
      further in the different disease states of prostate cancer.

PMID- 22584223
TI  - Overcoming residual interference in mental set switching: neural correlates and
      developmental trajectory.
AB  - Mental set switching is a key facet of executive control measured behaviorally
      through reaction time or accuracy (i.e., 'switch costs') when shifting among task
      types. One of several experimentally dissociable influences on switch costs is
      'task set inertia', conceptualized as the residual interference conferred when a
      previous stimulus-response tendency interferes with subsequent stimulus
      processing on a new task. Task set inertia is thought to represent the passive
      decay of the previous stimulus-response set from working memory, and its effects
      decrease with increased interstimulus interval. Closely spaced trials confer high
      task set inertia, while sparsely spaced trials confer low task set inertia. This
      functional magnetic resonance imaging (fMRI) study characterized, for the first
      time, two opposing brain systems engaged to resolve task set inertia: 1) a
      frontoparietal 'cortical control' network for overcoming high task set inertia
      interference and 2) a subcortical-motor network more active during trials with
      low task set inertia. These networks were distinct from brain regions showing
      general switching effects (i.e., switch>non-switch) and from other previously
      characterized interference effects. Moreover, there were ongoing maturational
      effects throughout adolescence for the brain regions engaged to overcome high
      task set inertia not seen for generalized switching effects. These novel findings
      represent a new avenue of exploration of cognitive set switching neural function.

PMID- 22584225
TI  - Familiarity modulates the functional relationship between theory of mind and
      autobiographical memory.
AB  - Qualitative and quantitative reviews of the neuroimaging literature show that
      overlapping brain regions support theory of mind (ToM) and autobiographical
      memory (AM). This overlap has been taken to suggest that individuals draw on past
      personal experiences to infer others' mental states, but work with amnesic people
      shows that ToM does not always depend on AM. One variable that may determine the
      extent to which one relies on AM when inferring another's thoughts and feelings
      during ToM is whether that individual is personally known. To test this
      possibility, participants were scanned with fMRI as they remembered past
      experiences in response to personal photos ('AM' condition) and imagined others'
      experiences in response to photos of personally familiar ('pToM' condition) and
      unfamiliar ('ToM' condition) others. Spatiotemporal Partial Least Squares was
      used to identify the spatial and temporal characteristics of neural activation
      patterns associated with AM, pToM, and ToM. We found that the brain regions
      supporting pToM more closely resembled those supporting AM relative to ToM
      involving unfamiliar others, with the greatest degree of overlap within midline
      regions. A complementary finding was the observation of striking differences
      between pToM and ToM such that midline regions associated with AM predominated
      during pToM, whereas more lateral regions associated with social semantic memory
      predominated during ToM. Overall, this study demonstrates that ToM involves a
      dynamic interplay between AM and social semantic memory that is biased towards AM
      when a personally familiar other is the subject of the mental state inference.

PMID- 22584226
TI  - Age related differences in the neural substrates of motor sequence learning after
      interleaved and repetitive practice.
AB  - Practice of tasks in an interleaved order generally induces superior retention
      compared to practicing in a repetitive order. Younger and older adults practiced
      serial reaction time tasks that were arranged in a repeated or an interleaved
      order on 2 successive days. Retention was tested on Day 5. For both groups,
      reaction times in the interleaved condition were slower than the repetitive
      condition during practice, but the reverse was true during retention on Day 5.
      After interleaved practice, changes in M1 excitability measured by paired-pulse
      TMS were greater than after repetitive practice, and this effect was more
      pronounced in older adults. Moreover, the increased M1 excitability correlated
      with the benefit of interleaved practice. BOLD signal was also increased for
      interleaved compared to repetitive practice in both groups. However, the pattern
      of correlations between increased BOLD during practice and subsequent benefit of
      the interleaved condition differed by group. In younger adults, dorsolateral
      prefrontal activity during practice was related to this benefit, while in older
      adults, activation in sensorimotor regions and rostral prefrontal cortex during
      practice correlated with the benefit of interleaving on retention. Older adults
      may engage compensatory mechanisms during interleaved practice such as increasing
      sensorimotor recruitment which in turn benefits learning.

PMID- 22584227
TI  - Influences of skull segmentation inaccuracies on EEG source analysis.
AB  - The low-conducting human skull is known to have an especially large influence on
      electroencephalography (EEG) source analysis. Because of difficulties segmenting
      the complex skull geometry out of magnetic resonance images, volume conductor
      models for EEG source analysis might contain inaccuracies and simplifications
      regarding the geometry of the skull. The computer simulation study presented here
      investigated the influences of a variety of skull geometry deficiencies on EEG
      forward simulations and source reconstruction from EEG data. Reference EEG data
      was simulated in a detailed and anatomically plausible reference model. Test
      models were derived from the reference model representing a variety of skull
      geometry inaccuracies and simplifications. These included erroneous skull holes,
      local errors in skull thickness, modeling cavities as bone, downward extension of
      the model and simplifying the inferior skull or the inferior skull and scalp as
      layers of constant thickness. The reference EEG data was compared to forward
      simulations in the test models, and source reconstruction in the test models was
      performed on the simulated reference data. The finite element method with high
      resolution meshes was employed for all forward simulations. It was found that
      large skull geometry inaccuracies close to the source space, for example, when
      cutting the model directly below the skull, led to errors of 20mm and more for
      extended source space regions. Local defects, for example, erroneous skull holes,
      caused non-negligible errors only in the vicinity of the defect. The study design
      allowed a comparison of influence size, and guidelines for modeling the skull
      geometry were concluded.

PMID- 22584228
TI  - Illusory movements prevent cortical disruption caused by immobilization.
AB  - Enforced limb disuse strongly disrupts the cortical networks that are involved in
      sensorimotor activities. This disruption causes a cortical reorganization that
      may be functionally maladaptive. In this study, we used functional magnetic
      resonance imaging (fMRI) to investigate whether it is possible to prevent this
      reorganization by compensating for the lack of actual kinesthetic perception with
      illusory movements induced by "neuromimetic" proprio-tactile feedback that is
      artificially delivered during immobilization. Sixteen healthy volunteers were
      equipped for five days with full-hand ortheses that prevented them from
      performing finger and hand movements but allowed for kinesthetic and tactile
      sensations. Eight participants received a twice-daily proprio-tactile treatment
      consisting of the perception of kinesthetic sensations resembling those felt
      during actual movements generated by miniature vibrators set in the ortheses at
      the finger and wrist levels. Eight untreated participants received no
      stimulation. The effects of hand immobilization and treatment were assessed by
      fMRI during a calibrated voluntary hand movement task and hand tactile
      stimulation before cast placement and immediately after cast removal. We found
      that the sensorimotor network was preserved in subjects who underwent this
      treatment during hand immobilization, while the sensorimotor network of untreated
      subjects was significantly altered. These findings suggest that sensory feedback
      and associated movement perception may counteract disuse-induced cortical plastic
      changes through recruitment of a large part of the cortical network used for
      actual performed movement. The possibility of guiding cortical plasticity with
      proprioceptive augmented feedback is potentially relevant for rehabilitation
      efforts.

PMID- 22584229
TI  - Left prefrontal cortex activation during sentence comprehension covaries with
      grammatical knowledge in children.
AB  - Children's language skills develop rapidly with increasing age, and several
      studies indicate that they use language- and age-specific strategies to
      understand complex sentences. In the present experiment, functional magnetic
      resonance imaging (fMRI) and behavioral measures were used to investigate the
      acquisition of case-marking cues for sentence interpretation in the developing
      brain of German preschool children with a mean age of 6 years. Short sentences
      were presented auditorily, consisting of a transitive verb and two case-marked
      arguments with canonical subject-initial or non canonical object-initial word
      order. Overall group results revealed mainly left hemispheric activation in the
      perisylvian cortex with increased activation in the inferior parietal cortex
      (IPC), and the anterior cingulate cortex (ACC) for object-initial compared to
      subject-initial sentences. However, single-subject analysis suggested two
      distinct activation patterns within the group which allowed a classification into
      two subgroups. One subgroup showed the predicted activation increase in the left
      inferior frontal gyrus (IFG) for the more difficult object-initial compared to
      subject-initial sentences, while the other group showed the reverse effect. This
      activation in the left IFG can be taken to reflect the degree to which adult-like
      sentence processing strategies, necessary to integrate case-marking information,
      are applied. Additional behavioral data on language development tests show that
      these two subgroups differ in their grammatical knowledge. Together with these
      behavioral findings, the results indicate that the use of a particular processing
      strategy is not dependent on age as such, but rather on the child's individual
      grammatical knowledge and the ability to use specific language cues for
      successful sentence comprehension.

PMID- 22584230
TI  - Contrast-enhanced functional blood volume imaging (CE-fBVI): enhanced sensitivity
      for brain activation in humans using the ultrasmall superparamagnetic iron oxide
      agent ferumoxytol.
AB  - Functional MRI (fMRI) brain studies performed in the presence of a steady-state
      or "blood pool" contrast agent yields activation maps that are weighted for
      cerebral blood volume (CBV). Previous animal experiments suggest significant
      contrast-to-noise ratio (CNR) improvements, but these studies have not yet been
      performed in humans due to the lack of availability of a suitable agent. Here we
      report the use of the USPIO ferumoxytol (AMAG Pharmaceuticals, Inc., Cambridge,
      MA) for functional brain activation in humans, termed contrast enhanced
      functional blood volume imaging (CE-fBVI). Four subjects were scanned during a
      unilateral finger tapping task with standard blood-oxygen level dependent (BOLD)
      imaging before contrast and CE-fBVI after contrast injection. The CE-fBVI
      response showed both a fast (5.8+/-1.3 s) and a slow (75.3+/-27.5 s) component of
      CBV response to stimuli. A significant CNR gain of approximately 2-3 was found
      for CE-fBVI compared to BOLD fMRI. Interestingly, less susceptibility-related
      signal dropouts were observed in the inferior frontal and temporal lobes with CE
      fBVI. The combination of higher CNR and better spatial specificity, enabled by CE
      fBVI using blood pool USPIO contrast agent opens the door to higher resolution
      brain mapping.

PMID- 22584231
TI  - Cortical activation during executed, imagined, observed, and passive wrist
      movements in healthy volunteers and stroke patients.
AB  - Motor imagery, passive movement, and movement observation have been suggested to
      activate the sensorimotor system without overt movement. The present study
      investigated these three covert movement modes together with overt movement in a
      within-subject design to allow for a fine-grained comparison of their abilities
      in activating the sensorimotor system, i.e. premotor, primary motor, and
      somatosensory cortices. For this, 21 healthy volunteers underwent functional
      magnetic resonance imaging (fMRI). In addition we explored the abilities of the
      different covert movement modes in activating the sensorimotor system in a pilot
      study of 5 stroke patients suffering from chronic severe hemiparesis. Results
      demonstrated that while all covert movement modes activated sensorimotor areas,
      there were profound differences between modes and between healthy volunteers and
      patients. In healthy volunteers, the pattern of neural activation in overt
      execution was best resembled by passive movement, followed by motor imagery, and
      lastly by movement observation. In patients, attempted overt execution was best
      resembled by motor imagery, followed by passive movement, and lastly by movement
      observation. Our results indicate that for severely hemiparetic stroke patients
      motor imagery may be the preferred way to activate the sensorimotor system
      without overt behavior. In addition, the clear differences between the covert
      movement modes point to the need for within-subject comparisons.

PMID- 22584233
TI  - Structural and functional neuroimaging phenotypes in dysbindin mutant mice.
AB  - Schizophrenia is a highly heritable psychiatric disorder that is associated with
      a number of structural and functional neurophenotypes. DTNBP1, the gene encoding
      dysbindin-1, is a promising candidate gene for schizophrenia. Use of a mouse
      model carrying a large genomic deletion exclusively within the dysbindin gene
      permits a direct investigation of the gene in isolation. Here, we use manganese
      enhanced magnetic resonance imaging (MEMRI) to explore the regional alterations
      in brain structure and function caused by loss of the gene encoding dysbindin-1.
      We report novel findings that uniquely inform our understanding of the
      relationship of dysbindin-1 to known schizophrenia phenotypes. First, in mutant
      mice, analysis of the rate of manganese uptake into the brain over a 24-hour
      period, putatively indexing basal cellular activity, revealed differences in
      dopamine rich brain regions, as well as in CA1 and dentate subregions of the
      hippocampus formation. Finally, novel tensor-based morphometry techniques were
      applied to the mouse MRI data, providing evidence for structural volume deficits
      in cortical regions, subiculum and dentate gyrus, and the striatum of dysbindin
      mutant mice. The affected cortical regions were primarily localized to the
      sensory cortices in particular the auditory cortex. This work represents the
      first application of manganese-enhanced small animal imaging to a mouse model of
      schizophrenia endophenotypes, and a novel combination of functional and
      structural measures. It revealed both hypothesized and novel structural and
      functional neural alterations related to dysbindin-1.

PMID- 22584232
TI  - It's All About You: an ERP study of emotion and self-relevance in discourse.
AB  - Accurately communicating self-relevant and emotional information is a vital
      function of language, but we have little idea about how these factors impact
      normal discourse comprehension. In an event-related potential (ERP) study, we
      fully crossed self-relevance and emotion in a discourse context. Two-sentence
      social vignettes were presented either in the third or the second person
      (previous work has shown that this influences the perspective from which mental
      models are built). ERPs were time-locked to a critical word toward the end of the
      second sentence which was pleasant, neutral, or unpleasant (e.g., A man knocks on
      Sandra's/your hotel room door. She/You see(s) that he has agift/tray/gunin his
      hand.). We saw modulation of early components (P1, N1, and P2) by self-relevance,
      suggesting that a self-relevant context can lead to top-down attentional effects
      during early stages of visual processing. Unpleasant words evoked a larger late
      positivity than pleasant words, which evoked a larger positivity than neutral
      words, indicating that, regardless of self-relevance, emotional words are
      assessed as motivationally significant, triggering additional or deeper
      processing at post-lexical stages. Finally, self-relevance and emotion interacted
      on the late positivity: a larger late positivity was evoked by neutral words in
      self-relevant, but not in non-self-relevant, contexts. This may reflect prolonged
      attempts to disambiguate the emotional valence of ambiguous stimuli that are
      relevant to the self. More broadly, our findings suggest that the assessment of
      emotion and self-relevance are not independent, but rather that they
      interactively influence one another during word-by-word language comprehension.

PMID- 22584234
TI  - Brain tissue water comes in two pools: evidence from diffusion and R2'
      measurements with USPIOs in non human primates.
AB  - Diffusion-weighted MRI of non-human primates revealed that USPIO Bulk Magnetic
      Susceptibility (BMS) T2' effects of Ultrasmall Superparamagnetic Particles with
      Iron Oxide (USPIO) in the brain cannot be explained by a single compartment
      model, as diffusion and T2' effects appear coupled: Apparent Diffusion
      Coefficient (ADC) values depend on USPIO concentration and relaxivity effects of
      USPIO decrease with the b value. On the other hand, USPIO and diffusion effects
      could be well uncoupled using a model consisting in a fast and a slow diffusion
      pool with different relaxivities. Diffusion-weighting acts as a filter which
      emphasizes the contribution of the slow pool when increasing b values (apparent
      decrease in ADC and R2'). Those results have implications for human studies using
      BMS contrast agents, as well as BOLD and diffusion fMRI.

PMID- 22584235
TI  - Single-trial EEG-fMRI coupling of the emotional auditory early posterior
      negativity.
AB  - Event-related potential (ERP) studies in the visual domain often report an
      emotion-evoked early posterior negativity (EPN). Studies in the auditory domain
      have recently shown a similar component. Little source localization has been done
      on the visual EPN, and no source localization has been done on the auditory EPN.
      The aim of the current study was to identify the neural generators of the
      auditory EPN using EEG-fMRI single-trial coupling. Data were recorded from 19
      subjects who completed three auditory choice reaction tasks: (1) a control task
      using neutral tones; (2) a prosodic emotion task involving the categorization of
      syllables; and (3) a semantic emotion task involving the categorization of words.
      The waveforms of the emotion tasks diverged from the neutral task over parietal
      scalp during a very early time window (132-156 ms) and later during a more
      traditional EPN time window (252-392 ms). In the EEG-fMRI analyses, the variance
      of the voltage in the earlier time window was correlated with activity in the
      medial prefrontal cortex, but only in the word task. In the EEG-fMRI analyses of
      the traditional EPN time window both emotional tasks covaried with activity in
      the left superior parietal lobule. Our results support previous parietal cortex
      source localization findings for the visual EPN, and suggest enhanced selective
      attention to emotional stimuli during the EPN time window.

PMID- 22584236
TI  - Touch and personality: extraversion predicts somatosensory brain response.
AB  - The Five-Factor-Model describes human personality in five core dimensions
      (extraversion, neuroticism, agreeableness, conscientiousness, and openness).
      These factors are supposed to have different neural substrates. For example, it
      has been suggested that behavioral differences between introverts and extraverts
      can be explained by the fact that introverts exhibit an inherent drive to
      compensate for overactive cortical activity in reticulo-thalamo-cortical
      pathways. The current study examined if responses in somatosensory cortices due
      to tactile stimulation are affected by personality traits. Based on previous
      studies and theoretical models we hypothesized a relationship of extraversion
      with somatosensory responses in primary somatosensory cortex (SI). In order to
      test this hypothesis we applied nonpainful tactile stimulation on the fingers of
      both hands of 23 healthy young participants (mean 25 years, standard deviation +/
      2.8 years). Personality traits were assessed according to the Five-Factor-Model
      (NEO-FFI). Neuromagnetic source imaging revealed that the cortical activity
      (dipole strengths) for sources in SI were closely associated with the personality
      trait extraversion. Thus, the less extraverted the participants were, the higher
      was the cortical activity in SI. This relationship was in particular valid for
      the right hemisphere. We conclude that personality seems to depend on primary
      cortex activity. Furthermore, our results provide further evidence for an inter
      hemispheric asymmetry of the social brain.

PMID- 22584224
TI  - A review and synthesis of the first 20 years of PET and fMRI studies of heard
      speech, spoken language and reading.
AB  - The anatomy of language has been investigated with PET or fMRI for more than 20
      years. Here I attempt to provide an overview of the brain areas associated with
      heard speech, speech production and reading. The conclusions of many hundreds of
      studies were considered, grouped according to the type of processing, and
      reported in the order that they were published. Many findings have been
      replicated time and time again leading to some consistent and undisputable
      conclusions. These are summarised in an anatomical model that indicates the
      location of the language areas and the most consistent functions that have been
      assigned to them. The implications for cognitive models of language processing
      are also considered. In particular, a distinction can be made between processes
      that are localized to specific structures (e.g. sensory and motor processing) and
      processes where specialisation arises in the distributed pattern of activation
      over many different areas that each participate in multiple functions. For
      example, phonological processing of heard speech is supported by the functional
      integration of auditory processing and articulation; and orthographic processing
      is supported by the functional integration of visual processing, articulation and
      semantics. Future studies will undoubtedly be able to improve the spatial
      precision with which functional regions can be dissociated but the greatest
      challenge will be to understand how different brain regions interact with one
      another in their attempts to comprehend and produce language.

PMID- 22584237
TI  - 5-HTTLPR status predictive of neocortical 5-HT4 binding assessed with
      [(11)C]SB207145 PET in humans.
AB  - Serotonin (5-HT) is a neuromodulator affecting myriad aspects of personality and
      behavior and has been implicated in the pathophysiology of affective disorders
      including depression and anxiety. The 5-HTTLPR is a common genetic polymorphism
      within the promoter region of the gene coding for the serotonin transporter such
      that the S allele is associated with reduced transcriptional efficacy compared to
      the L allele, potentially contributing to increased serotonin levels. In humans,
      this genetic variant has been linked to inter-individual variability in risk for
      affective disorders, related aspects of personality and brain function including
      response to threat. However, its effects on aspects of serotonin signaling in
      humans are not fully understood. Studies in animals suggest that the 5-HT 4
      receptor (5-HT(4)) shows a monotonic inverse association with long-term changes
      in serotonin levels indicating that it may be a useful measure for identifying
      differences in serotonergic neurotransmission. In 47 healthy adults we evaluated
      the association between 5-HTTLPR status and in vivo 5-HT(4) receptor binding
      assessed with [(11)C]SB207145 positron emission tomography (PET). We observed a
      significant association within the neocortex where [(11)C]SB207145 binding was 9%
      lower in S carriers compared to LL homozygotes. We did not find evidence for an
      effect of season or a season-by-5-HTTLPR interaction effect on regional
      [(11)C]SB207145 binding. Our findings are consistent with a model wherein the 5
      HTTLPR S allele is associated with relatively increased serotonin levels. These
      findings provide novel evidence supporting an effect of 5-HTTLPR status on
      serotonergic neurotransmission in adult humans. There were no indications of
      seasonal effects on serotonergic neurotransmission.

PMID- 22584238
TI  - Automated cognome construction and semi-automated hypothesis generation.
AB  - Modern neuroscientific research stands on the shoulders of countless giants.
      PubMed alone contains more than 21 million peer-reviewed articles with 40-50,000
      more published every month. Understanding the human brain, cognition, and disease
      will require integrating facts from dozens of scientific fields spread amongst
      millions of studies locked away in static documents, making any such integration
      daunting, at best. The future of scientific progress will be aided by bridging
      the gap between the millions of published research articles and modern databases
      such as the Allen brain atlas (ABA). To that end, we have analyzed the text of
      over 3.5 million scientific abstracts to find associations between
      neuroscientific concepts. From the literature alone, we show that we can blindly
      and algorithmically extract a "cognome": relationships between brain structure,
      function, and disease. We demonstrate the potential of data-mining and cross
      platform data-integration with the ABA by introducing two methods for semi
      automated hypothesis generation. By analyzing statistical "holes" and
      discrepancies in the literature we can find understudied or overlooked research
      paths. That is, we have added a layer of semi-automation to a part of the
      scientific process itself. This is an important step toward fundamentally
      incorporating data-mining algorithms into the scientific method in a manner that
      is generalizable to any scientific or medical field.

PMID- 22584239
TI  - Carbamazepine-induced non-epileptic myoclonus and tic-like movements.
AB  - Carbamazepine-induced abnormal movements have been reported in children and adult
      patients, and both non-epileptic myoclonus and tic-like movements have been
      reported in the same patient. Although a pathogenetic mechanism underlying
      carbamazepine-induced epileptic negative myoclonus has been proposed, a causative
      role of carbamazepine for positive myoclonus has not been fully identified. Here,
      we describe the video-documented case of an adult patient with non-epileptic
      myoclonus and tic-like movements persisting for 21 years, which appeared after he
      started carbamazepine treatment at 10 years of age. [Published with
      videosequences].

PMID- 22584241
TI  - Frequency of adverse reactions to first- and second-line anti-tuberculosis
      chemotherapy in a Korean cohort.
AB  - OBJECTIVE: To determine the frequency of and risk factors for major adverse drug
      reactions (MADRs) associated with anti-tuberculosis treatment at a tuberculosis
      (TB) referral hospital in the Republic of Korea. METHODS: Data from an ongoing
      natural history cohort study were analyzed  for permanent regimen changes due to
      adverse drug reactions and confirmed by chart review. RESULTS: Among 655
      subjects, there were 132 MADRs in 112 (17%) subjects. The most common MADRs were
      gastrointestinal (n = 53), musculoskeletal (n = 22), psychiatric (n = 10), 
      visual (n = 9) and peripheral neuropathic (n = 8). MADRs were more frequent in
      subjects being treated with second-line regimens (16%) compared to first-line
      regimens (2.5%). Drugs frequently associated with MADRs were amikacin (3/10,
      30%), linezolid (8/29, 28%), para-aminosalicylic  acid (47/192, 24%),
      pyrazinamide (31/528, 5.8%), macrolides (2/44, 4.5%) and cycloserine (12/272,
      4.4%). Fluoroquinolones accounted for a single MADR (1/377, 0.003%), despite
      widespread usage. In multivariate analysis, infection with multi- or extensively
      drug-resistant disease and previous  history of anti-tuberculosis treatment were
      risk factors for MADR, with adjusted hazard ratios of respectively 2.2 (P = 0.02)
      and 1.6 (P = 0.04). CONCLUSION: MADRs are common during anti-tuberculosis
      chemotherapy in this population, occurring in more than one in six subjects.  New
      and less toxic agents to treat drug-resistant TB are urgently needed.

PMID- 22584244
TI  - Surgical management of tympanojugular paragangliomas with intradural extension,
      with a proposed revision of the Fisch classification.
AB  - BACKGROUND: Tympanojugular paragangliomas (TJPs) with intradural extension can be
      successfully treated by a single or staged procedure with low surgical morbidity.
      OBJECTIVES: To present the clinical findings and treatment methods used for
      surgically treating TJP with intradural extension, as well as to discuss the
      complications of treatment and the relative merits of single versus staged
      surgery by using a comprehensive literature review comparing objective outcome
      measures. STUDY DESIGN: A retrospective case review of 45 cases of TJP with
      intradural extension. SETTING: A quaternary skull base and neurotologic center.
      MATERIALS AND METHODS: The charts of 45 patients with Fisch classification class
      C or D TJP with intradural extension, who were operated on from April 1988 to
      April 2010, were analyzed. Clinical findings and preoperative lower cranial nerve
      (LCN) palsy as well as postoperative totality of resection, postoperative LCN
      palsy and complications were studied. The types, indications, and distribution of
      staged procedures were also analyzed. RESULTS: Out of 45 cases, 22 were C3di2.
      The IX and X cranial nerves were the commonest nerves affected preoperatively.
      Preoperative internal carotid artery management was performed in 16 cases. Twenty
      nine cases had a single procedure and 16 had a staged procedure. The main
      indication for staged procedures was intradural extension of 2 cm or more. The
      infratemporal fossa approach (ITFA) type A was the main procedure in all cases.
      Overall, total resection was achieved in 68.8% of cases with postoperative
      cerebrospinal fluid leak in 4.4% cases. Postoperative House-Beckmann grade I-III
      facial nerve status was maintained in 80% of cases, and overall LCN preservation
      rate was 56.9%. There were no cases requiring tracheostomy, and 3 cases required
      delayed phonosurgical procedures to improve their voice. CONCLUSIONS: TJP with
      intradural extension can be successfully managed with the judicious use of staged
      procedures to reduce the incidence of postoperative cerebrospinal fluid leak. The
      ITFA did not cause an excessively high rate of facial nerve palsy, and the
      overall total resection and LCN preservation rate compares very favorably with
      previously published data.

PMID- 22584245
TI  - Cholesteryl ester transfer protein and ATP-binding cassette transporter A1
      genotype alter the atorvastatin and simvastatin efficacy: time for genotype
      guided therapy?
AB  - We compared the efficacy of atorvastatin with simvastatin according to
      cholesteryl ester transfer protein (CETP) and adenosine triphosphate-binding
      cassette transporter A1 (ABCA1) genes. Patients treated with atorvastatin (n =
      254) or simvastatin (n = 332) were genotyped for CETP (TaqIB and I405V) and ABCA1
      (R219K) genetic variants. For genotype B1B2, atorvastatin compared with
      simvastatin treatment resulted in a greater decrease in total cholesterol (35.4%
      vs 31.6%, P = .035) and a lower increase in high-density lipoprotein cholesterol
      (2% vs 8%, P = .05). For genotype B2B2, atorvastatin compared with simvastatin
      treatment resulted in a lower decrease in low-density lipoprotein cholesterol
      (31.85 vs 42%, P = .029). For genotypes RR and KK, atorvastatin compared with
      simvastatin treatment resulted in a greater decrease of triglycerides (27% vs 17%
      and 35% vs 15%, respectively; P = .02 for all comparisons). The TaqIB and R219K
      (opposite to I405V) gene polymorphisms seem to modify the response to lipid
      lowering therapy with simvastatin or atorvastatin treatment.

PMID- 22584246
TI  - Increased carotid and brachial intima-media thickness is related to diffuse
      coronary involvement rather than focal lesions.
AB  - We evaluated whether an increased carotid intima-media thickness (cIMT) and
      brachial artery IMT (bIMT) are related to diffuse coronary involvement rather
      than focal lesions. Patients (n = 88) with at least 1 significant lesion of the
      main epicardial coronary arteries (>=50%) were included in the present study. We
      used a novel score based on length and mean narrowing of all lesions in order to
      predict diffuse coronary involvement. Both cIMT and bIMT were higher in patients
      with long coronary lesion than focal lesion (P < .001). The patients with long
      coronary lesion had a higher rate of total coronary involvement than patients
      with focal lesion (P < .001). The cIMT had a higher correlation with total
      atherosclerotic burden in the coronary vasculature (r = .495, P < .001) and the
      longest lesion length (r = .489, P < .001) than cardiovascular risk factor score
      (r = .453, P < .001 and r = .324, P = .012, respectively). These findings may be
      valuable for clarifying the prognostic value of IMT measurements.

PMID- 22584247
TI  - A high prevalence of carotid artery stenosis in male patients older than 65
      years, irrespective of presenting clinical manifestation of atherosclerotic
      diseases.
AB  - This study investigated the prevalence of carotid artery stenosis (CS) and the
      association with various risk factors in male patients (>65 years) diagnosed with
      cardiovascular diseases. Duplex sonography of the carotid arteries was performed
      in 434 of 473 eligible patients of whom 118 (27.8%) patients had significant CS
      >=50%. The prevalence and severity of CS did not differ between patients who
      presented with neurological symptoms or acute coronary syndrome/peripheral artery
      disease (30.8% vs 25.9%, respectively). Among patients with CS, a higher rate of
      current smoking, a higher systolic blood pressure, and a lower glomerular
      filtration rate were observed compared with patients without CS. A history of
      coronary artery bypass graft was a significant predictor of the presence of CS (P
      = .003, odds ratio [OR] = 2.70 [1.40-5.19]). The prevalence of CS in elderly
      males with manifest atherosclerotic disease is high, irrespective of presenting
      clinical manifestation.

PMID- 22584248
TI  - Steady-state solutions of cell volume in a cardiac myocyte model elaborated for
      membrane excitation, ion homeostasis and Ca2+ dynamics.
AB  - The cell volume continuously changes in response to varying physiological
      conditions, and mechanisms underlying volume regulation have been investigated in
      both experimental and theoretical studies. Here, general formulations concerning
      cell volume change are presented in the context of developing a comprehensive
      cell model which takes Ca(2+) dynamics into account. Explicit formulas for charge
      conservation and steady-state volumes of the cytosol and endoplasmic reticulum
      (ER) are derived in terms of membrane potential, amount of ions, Ca(2+)-bound
      buffer molecules, and initial cellular conditions. The formulations were applied
      to a ventricular myocyte model which has plasma-membrane Ca(2+) currents with
      dynamic gating mechanisms, Ca(2+)-buffering reactions with diffusive and non
      diffusive buffer proteins, and Ca(2+) uptake into or release from the
      sarcoplasmic reticulum (SR) accompanied by compensatory cationic or anionic
      currents through the SR membrane. Time-dependent volume changes in cardiac
      myocytes induced by varying extracellular osmolarity or by action potential
      generation were successfully simulated by the novel formulations. Through
      application of bifurcation analysis, the existence and uniqueness of steady-state
      solutions of the cell volume were validated, and contributions of individual ion
      channels and transporters to the steady-state volume were systematically
      analyzed. The new formulas are consistent with previous fundamental theory
      derived from simple models of minimum compositions. The new formulations may be
      useful for examination of the relationship between cell function and volume
      change in other cell types.

PMID- 22584249
TI  - A model of crosslink kinetics in the expanding plant cell wall: yield stress and
      enzyme action.
AB  - The plant primary cell wall is a composite material containing stiff cellulose
      microfibrils that are embedded within a pectin matrix and crosslinked through a
      network of hemicellulose polymers. This microstructure endows the wall with
      nonlinear anisotropic mechanical properties and allows enzymatic regulation of
      expansive cell growth. We present a mathematical model of hemicellulose crosslink
      dynamics in an expanding cell wall incorporating strain-enhanced breakage and
      enzyme-mediated crosslink kinetics. The model predicts the characteristic
      yielding behaviour in the relationship between stress and strain-rate seen
      experimentally, and suggests how the effective yield and extensibility of the
      wall depend on microstructural parameters and on the action of enzymes of the XTH
      and expansin families. The model suggests that the yielding behaviour
      encapsulated in the classical Lockhart equation can be explained by the strongly
      nonlinear dependence of crosslink breakage rate on crosslink elongation. The
      model also demonstrates how enzymes that target crosslink binding can be
      effective in softening the wall in its pre-yield state, whereas its post-yield
      extensibility is determined primarily by the pectin matrix.

PMID- 22584250
TI  - A comparison of two immunoassay methods for the measurement of maternal serum
      placental growth factor in early pregnancy.
AB  - OBJECTIVES: To compare the DELFIA Xpress and Quantikine ELISA placental growth
      factor (PlGF) immunoassay platforms by analysing the same set of early first
      trimester maternal serum samples from cases with trisomy 21 and euploid controls.
      METHODS: Thirty-seven trisomy 21 cases and 243 euploid control serum samples,
      drawn at 8(+0) to 10(+6) weeks of gestation, were reanalysed by Quantikine PlGF
      ELISA following original analysis on the DELFIA Xpress platform. RESULTS: PlGF
      levels increased with gestation in the euploid controls when measured on both
      platforms, although raw levels were in general lower on the DELFIA Xpress. After
      conversion to multiples of the median (MoMs), PlGF was increased in trisomy 21
      cases when measured on the DELFIA Xpress platform (euploid: 1.00 MoM, trisomy 21:
      1.32 MoM, p < 0.0001) but unchanged when measured on the Quantikine ELISA
      (euploid: 1.01 MoM, trisomy 21: 1.06 MoM, p = 0.84). CONCLUSIONS: Discrepancies
      exist in the measurement of PlGF when performed on these different platforms,
      which may to some extent contribute to the inconsistencies found in the
      literature with regard to PlGF in trisomy 21 pregnancies.

PMID- 22584252
TI  - The increased cellular uptake and biliary excretion of curcumin by quercetin: a
      possible role of albumin binding interaction.
AB  - Curcumin and quercetin are natural compounds with a wide spectrum of activities,
      including antioxidant and anticancer activities. In this study, the combined
      effect of the two compounds was investigated, with special emphasis on the
      pharmacokinetics of curcumin by the quercetin-induced changes in the albumin
      binding of curcumin. We evaluated the effect of quercetin on the binding of
      curcumin to albumin and on the uptake of curcumin into the cells of the human
      colon carcinoma cell line WiDr. In addition, we also investigated changes in the
      in vivo pharmacokinetics of curcumin and curcumin sulfate (the major metabolite
      of curcumin) coadministered with quercetin. We found that quercetin inhibited the
      binding of curcumin to albumin and increased the uptake of curcumin into WiDr
      cells, the human colon carcinoma cell. The quercetin-induced increased uptake
      (1.6-fold) of curcumin into WiDr cells was also confirmed by an ex vivo study.
      The in vivo pharmacokinetics of curcumin showed obvious changes when it was
      coadministered with quercetin, with the significantly lower plasma concentration
      and greater biliary excretion of curcumin and curcumin sulfate. The present study
      suggests that quercetin could enhance the cellular uptake of curcumin and
      modulate in vivo pharmacokinetics of curcumin, and it could be related to albumin
      binding interaction.

PMID- 22584253
TI  - FcRn affinity-pharmacokinetic relationship of five human IgG4 antibodies
      engineered for improved in vitro FcRn binding properties in cynomolgus monkeys.
AB  - The pH-dependent binding of IgGs to the neonatal Fc receptor (FcRn) plays a
      critical role in regulating IgG homeostasis in vivo. Enhancing interactions
      between Fc and FcRn via protein engineering has been successfully used as an
      approach for improving the pharmacokinetics of monoclonal antibodies (mAbs).
      Although the quantitative translatability of the in vitro FcRn affinity
      enhancement to an in vivo pharmacokinetic benefit has been supported by several
      studies, there are also published reports indicating a disconnect in this
      relation. The body of literature suggests there are likely additional biochemical
      and biophysical properties of the mAbs along with their FcRn affinity that
      influence the in vivo pharmacokinetics. Herein, we more broadly evaluate the in
      vitro Fc-FcRn interactions and biochemical properties of five humanized IgG4
      antibodies each with two Fc variant sequences (T250Q/M428L and V308P) and their
      corresponding pharmacokinetics in cynomolgus monkeys. Our findings indicate that
      the FcRn affinity-pharmacokinetic relationship does not show a direct correlation
      either across different IgGs or between the two variant sequences within a
      platform. Other parameters that have been suggested to contribute to mAb
      pharmacokinetic properties, such as the pH-dependent dissociation of the FcRn-IgG
      complexes, mAb biophysical properties, and nonspecific/charge binding
      characteristics of the mAbs, also did not independently explain the differing
      pharmacokinetic behaviors. Our results suggest that there is likely not a single
      in vitro parameter that readily predicts in vivo pharmacokinetics, but that the
      relative contribution and interplay of several factors along with the FcRn
      binding affinity are important determinants of mAb pharmacokinetic properties.

PMID- 22584254
TI  - Role of the intestinal peptide transporter PEPT1 in oseltamivir absorption: in
      vitro and in vivo studies.
AB  - It was reported that oseltamivir (Tamiflu) absorption was mediated by human
      peptide transporter (hPEPT) 1. Understanding the exact mechanism(s) of absorption
      is important in the context of drug-drug and diet-drug interactions. Hence, we
      investigated the mechanism governing the intestinal absorption of oseltamivir and
      its active metabolite (oseltamivir carboxylate) in wild-type [Chinese hamster
      ovary (CHO)-K1] and hPEPT1-transfected cells (CHO-PEPT1), in pharmacokinetic
      studies in juvenile and adult rats, and in healthy volunteers. In vitro cell
      culture studies showed that the intracellular accumulation of oseltamivir and its
      carboxylate into CHO-PEPT1 and CHO-K1 was always similar under a variety of
      experimental conditions, demonstrating that these compounds are not substrates of
      hPEPT1. Furthermore, neither oseltamivir nor its active metabolite was capable of
      inhibiting Gly-Sar uptake in CHO-PEPT1 cells. In vivo pharmacokinetic studies in
      juvenile and adult rats showed that the disposition of oseltamivir and
      oseltamivir carboxylate, after oral administration of oseltamivir, was sensitive
      to the feed status but insensitive to the presence of milk and Gly-Sar. Moreover,
      oseltamivir and oseltamivir carboxylate exhibited significantly higher exposure
      in rats under fasted conditions than under fed conditions. In humans, oral dosing
      after a high-fat meal resulted in a statistically significant but moderate lower
      exposure than after an overnight fasting. This change has no clinical
      implications. Taken together, the results do not implicate either rat Pept1 or
      hPEPT1 in the oral absorption of oseltamivir.

PMID- 22584255
TI  - Inhibition of P-glycoprotein leads to improved oral bioavailability of compound
      K, an anticancer metabolite of red ginseng extract produced by gut microflora.
AB  - Ginsenosides are hydrolyzed extensively by gut microflora after oral
      administration, and their metabolites are pharmacologically active against lung
      cancer cells. In this study, we measured the metabolism of various ginsenosides
      by gut microflora and determined the mechanisms responsible for the observed
      pharmacokinetic behaviors of its active metabolite, Compound K (C-K). The results
      showed that biotransformation into C-K is the major metabolic pathway of
      ginsenosides after the oral administration of the red ginseng extract containing
      both protopanaxadiol and protopanaxatriol ginsenosides. Pharmacokinetic studies
      in normal mice showed that C-K exhibited low oral bioavailability. To define the
      mechanisms responsible for this low bioavailability, two P-glycoprotein (P-gp)
      inhibitors, verapamil and cyclosporine A, were used, and their presence
      substantially decreased C-K's efflux ratio in Caco-2 cells (from 26.6 to <3) and
      significantly increased intracellular concentrations (by as much as 40-fold).
      Similar results were obtained when transcellular transport of C-K was determined
      using multidrug resistance 1 (MDR1)-overexpressing Madin-Darby canine kidney II
      cells. In MDR1a/b(-/-) FVB mice, its plasma C(max) and AUC(0-24h) were increased
      substantially by 4.0- and 11.7-fold, respectively. These increases appear to be
      due to slower elimination and faster absorption of C-K in MDR1a/b(-/-) mice. In
      conclusion, C-K is the major active metabolite of ginsenosides after microflora
      hydrolysis of primary ginsenosides in the red ginseng extract, and
      inhibition/deficiency of P-gp can lead to large enhancement of its absorption and
      bioavailability.

PMID- 22584256
TI  - Efficient radiative and nonradiative energy transfer from proximal CdSe/ZnS
      nanocrystals into silicon nanomembranes.
AB  - We demonstrate efficient excitonic sensitization of crystalline Si nanomembranes
      via combined effects of radiative (RET) and nonradiative (NRET) energy transfer
      from a proximal monolayer of colloidal semiconductor nanocrystals. Ultrathin, 25
      300 nm Si films are prepared on top of insulating SiO(2) substrates and grafted
      with a monolayer of CdSe/ZnS nanocrystals via carboxy-alkyl chain linkers. The
      wet chemical preparation ensures that Si surfaces are fully passivated with a
      negligible number of nonradiative surface state defects and that the separation
      between nanocrystals and Si is tightly controlled. Time-resolved
      photoluminescence measurements combined with theoretical modeling allow us to
      quantify individual contributions from RET and NRET. Overall efficiency of ET
      into Si is estimated to exceed 85% for a short distance of about 4 nm from
      nanocrystals to the Si surface. Effective and longer-range radiative coupling of
      nanocrystal's emission to waveguiding modes of Si films is clearly revealed. This
      demonstration supports the feasibility of an advanced thin-film hybrid solar cell
      concept that relies on energy transfer between strong light absorbers and
      adjacent high-mobility Si layers.

PMID- 22584257
TI  - Genetic variants at the ITPA locus protect against ribavirin-induced hemolytic
      anemia and dose reduction in an HCV G2/G3 cohort.
AB  - OBJECTIVES: Two functional genetic variants in the inosine triphosphatase (ITPA)
      gene have been shown to be strongly associated with protection from ribavirin
      (RBV)-induced hemolysis. We aimed at evaluating this finding in a chronic
      hepatitis C genotype 2/3 cohort with a predominance of genotype 3 patients where
      available data are scarce. A second objective was to determine whether a
      protective association translated into the need for RBV reduction and hence a
      possible impact on treatment response. METHODS: Overall, 457 patients were
      recruited from two trials of genotype 2/3 patients treated with pegylated
      interferon alpha-2b and weight-based RBV. rs1127354 and rs7270101 were genotyped
      and a composite ITPAase deficiency variable was graded according to the two
      single nucleotide polymorphisms. The primary endpoints were hemoglobin (Hb)
      decline from baseline and Hb decline of more than 3 g/dl at week 4. RESULTS: Both
      single nucleotide polymorphisms and the composite ITPAase deficiency variable
      were strongly and independently associated with protection from a decline in Hb
      at week 4 in multivariate linear regression models (Prs1127354=7.0*10,
      Prs7270101=0.0036, PITPase deficiency variable =6.3*10). Patients with any degree
      of reduced ITPAase activity were less likely to have their RBV dose reduced (odds
      ratio 0.39, 95% confidence interval 0.16-0.96, P=0.040), although this did not
      translate into increased rapid viral response or sustained viral response
      (Prvr=0.93, Psvr=0.22). CONCLUSION: We have confirmed a strong association
      between functional ITPA variants and RBV-induced hemolysis and showed protection
      from RBV dose reduction, although this did not translate into increased rapid
      viral response or sustained viral response.

PMID- 22584258
TI  - CUL4B ubiquitin ligase in mouse development: a model for human X-linked mental
      retardation syndrome?
AB  - CUL4B, a member of the cullin-RING ubiquitin ligase family, is frequently mutated
      in X-linked mental retardation (XLMR) patients. The study by Liu et al. showed
      that Cul4b plays an essential developmental role in the extra-embryonic tissues,
      while it is dispensable in the embryo proper during mouse embryogenesis. Viable
      Cul4b-null mice provide the first animal model to study neuronal and behavioral
      deficiencies seen in human CUL4B XLMR patients.

PMID- 22584259
TI  - Fractional exhaled nitric oxide (FeNO) may predict exercise-induced
      bronchoconstriction (EIB) in schoolchildren with atopic asthma.
AB  - BACKGROUND: There is a need for the performance of exercise-induced
      bronchoconstriction (EIB) tests in the monitoring of childhood asthma control. We
      aimed to evaluate whether in children with atopic asthma, EIB can be predicted by
      one or more of the following parameters or by their combination: fractional
      exhaled nitric-oxide (FeNO), allergy profile, asthma treatment, total IgE serum
      concentration and eosinophil blood count (EBC). METHODS: It was a retrospective,
      cross-sectional study. We evaluated data from medical documentation of children
      with atopic asthma who had performed standardized spirometric exercise challenge
      test. RESULTS: One hundred and twenty six patients with atopic asthma, aged 5-18,
      were included in the analysis. There were two groups of patients: the EIB group
      (n=54) and the no-EIB group (n=72). The median FeNO level prior to exercise in
      the EIB group was 27.6 vs. 16.3 ppb in the no-EIB group (p=0.002). FeNO level
      higher than 16 ppb had the highest diagnostic value to confirm EIB. When using
      the FeNO level of >16 ppb, the sensitivity, specificity, negative predictive and
      positive predictive values for EIB were 83%, 46.9%, 74.2%, and 60%, respectively.
      In the EIB group, the degree of FeNO elevation did correlate positively with the
      absolute fall in FEV(1) (p=0.002; r=0.45). The FeNO value of >16 ppb, EBC value
      of >350 cell/mm(3) and allergy to house dust mites presented the highest odds
      ratios of EIB. However, the FeNO value of >16 ppb was the only independent odds
      ratio of EIB. CONCLUSIONS: Elevated FeNO level increased the odds of EIB in
      asthmatic schoolchildren, independently of other asthma severity markers and the
      intensity of anti-asthma therapy. It seems likely that FeNO measurement may act
      as a screening tool and help to prevent under-diagnosis and under-treatment of
      exercise-induced bronchoconstriction in schoolchildren with atopic asthma.

PMID- 22584261
TI  - Voltammetric behavior of theophylline and its determination at multi-wall carbon
      nanotube paste electrode.
AB  - The voltammetric behavior of theophylline was investigated using cyclic and
      differential-pulse voltammetric techniques. The cyclic voltammetric results
      indicate that multi-wall carbon nanotube paste electrode can remarkably enhance
      electrocatalytic activity toward the oxidation of theophylline in pH 3.0
      phosphate buffer solution than the carbon paste electrode. The oxidation of
      theophylline was observed to be a two-electron process, irreversible with
      diffusion character. Effects of anodic peak potential (E(p)), anodic peak current
      (I(p)) and heterogeneous rate constant (k(o)) have been discussed. Under optimal
      conditions, the anodic peak current was proportional to theophylline
      concentration in the range of 2.0*10(-6) to 1.5*10(-4)M with a detection limit of
      1.97*10(-8)M using differential pulse voltammetry. The proposed method was
      employed to determine theophylline in pharmaceutical formulations and urine as a
      real sample.

PMID- 22584260
TI  - Comparative evaluation of the effect of tricyclic antidepressants on inducible
      nitric oxide synthase expression in neuropathic pain model.
AB  - The analgesic effect of acute i.p. administration of amitriptyline
      (norepinepherine and serotonin reuptake inhibitor), clomipramine (serotonin
      reuptake inhibitor) and desipramine (norepinepherine reuptake inhibitor) was
      studied in chronic constriction injury (CCI) model of sciatic nerve in rats and
      mRNA and protein expression of inducible nitric oxide synthase (iNOS) were also
      investigated. Acute treatment with amitriptyline and clomipramine produced
      antinociceptive effects after sciatic nerve injury and blockade of norepinephrine
      reuptake using desipramine did not demonstrate antinociceptive effects. The
      antinociceptive effect of amitriptyline, not clomipramine, was augmented by the
      selective iNOS inhibitor, aminoguanidine. Amitriptyline inhibited iNOS mRNA and
      protein expression in cerebellum and hippocampus. However, desipramine altered
      neither iNOS expression at mRNA level nor at post-transcriptional level. Based on
      our experimental findings, we conclude that the analgesic effect of the dual
      norepinepherine and serotonin reuptake inhibitor, amitriptyline, is partially due
      to inhibition of central iNOS.

PMID- 22584262
TI  - Self-assembly of Fmoc-diphenylalanine inside liquid marbles.
AB  - Liquid marbles made from Lycopodium clavatum spores are used to encapsulate
      aqueous solutions of 9-fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF).
      Acidification of the Fmoc-FF solution at the liquid/air interface of the liquid
      marble triggers the self-assembly of ribbon-like peptide fibrils into an
      ultrathin peptide membrane (50-500 nm). The membrane incorporates the lycopodium
      microparticles and as a result stabilizes the liquid marble against collapse,
      that could otherwise occur through particle disintegration at the floating
      interphase. Ultrathin nanostructured peptide membrane formation at the liquid/air
      interface is also observed within artificial microstructured floating objects.
      Thus, peptide membranes formed were inspected by SEM and TEM. Electron
      diffraction data reveal information about the molecular organization inside the
      oligopeptide membranes.

PMID- 22584263
TI  - Effects of glyceryl glucoside on AQP3 expression, barrier function and hydration
      of human skin.
AB  - BACKGROUND/AIM: Aquaporins (AQPs) present in the epidermis are essential
      hydration-regulating elements controlling cellular water and glycerol transport.
      In this study, the potential of glyceryl glucoside [GG; alpha-D-glucopyranosyl
      alpha-(1->2)-glycerol], an enhanced glycerol derivative, to increase the
      expression of AQP3 in vitro and ex vivo was evaluated. METHODS: In vitro studies
      with real-time RT-PCR and FACS measurements were performed to test the induction
      by GG (3% w/v) of AQP3 mRNA and protein in cultured human keratinocytes. GG
      containing formulations were applied topically to volunteer subjects and suction
      blister biopsies were analyzed to assess whether GG (5%) could penetrate the
      epidermis of intact skin, and subsequently upregulate AQP3 mRNA expression and
      improve barrier function. RESULTS: AQP3 mRNA and protein levels were
      significantly increased in cultured human keratinocytes. In the studies on
      volunteer subjects, GG significantly increased AQP3 mRNA levels in the skin and
      reduced transepidermal water loss compared with vehicle-controlled areas.
      CONCLUSION: GG promotes AQP3 mRNA and protein upregulation and improves skin
      barrier function, and may thus offer an effective treatment option for dehydrated
      skin.

PMID- 22584264
TI  - Solid waste characterization in Ketao, a rural town in Togo, West Africa.
AB  - In Africa the majority of solid waste data is for big cities. Small and rural
      towns are generally neglected and waste data from these areas are often
      unavailable, which makes planning a proper solid waste management difficult. This
      paper presents the results from two waste characterization projects conducted in
      Ketao, a rural town in Togo during the rainy season and the dry season in 2010.
      The seasonal variation has a significant impact on the waste stream. The
      household waste generation rate was estimated at 0.22 kg person(-1) day(-1) in
      the dry season and 0.42 in the rainy season. Likewise, the waste moisture content
      was 4% in the dry season while it was 33-63% in the rainy season. The waste
      consisted mainly of soil and dirt characterized as 'other' (41%), vegetables and
      putrescibles (38%) and plastic (11%). In addition to these fractions,
      considerable amounts of material are either recycled or reused locally and do not
      enter the waste stream. The study suggests that additional recycling is not
      feasible, but further examination of the degradability of the organic fraction is
      needed in order to assess whether the residual waste should be composed or
      landfilled.

PMID- 22584265
TI  - Identification of junk buyers' contribution to recycling of household waste in
      Hanoi, Vietnam, through a physical composition analysis.
AB  - Even in developing countries, the amount of containers and packaging waste are
      increasing in line with population concentration and lifestyle changes in urban
      areas. This can cause serious problems for the disposal of municipal solid waste.
      Through a physical composition analysis of household waste in Hanoi, the capital
      of Vietnam, this study aimed to identify the contribution made by junk buyers to
      recycling. Interviews on the handling of recyclable waste by households were
      conducted. About 232 kg of recyclable waste was sampled from a total of 115
      households, and about 230 kg of municipal solid waste was sampled from a total of
      101 households and sorted into 69 categories for measurement by volume and
      weight. The interview survey revealed that a high proportion of households tended
      to routinely store recyclable waste for sale or donation to junk buyers. Junk
      buyers accounted for 8.8% of recycling by weight or 26.0% by volume according to
      the results of the physical composition analysis. In addition, the results
      suggested that containers and packaging waste accounted for the largest
      proportion of household waste by volume. Junk buyers recycled 25.5% by weight of
      containers and packaging waste. In the formulation of new plans for municipal
      solid waste management to improve the current situation and handle future
      challenges, the role of the informal sector should be monitored carefully and
      reliable data on recyclable waste should be collected continuously.

PMID- 22584266
TI  - Chemical and sewage sludge co-incineration in a full-scale MSW incinerator: toxic
      trace element mass balance.
AB  - Co-incineration of sludges with MSW is a quite common practice in Europe. This
      paper illustrates a case of co-incineration of both sewage sludges and chemical
      sludges, the latter obtained from drinking water production, in a waste-to-energy
      (WTE) plant located in northern Italy and equipped with a grate furnace, and
      compares the toxic trace elements mass balance with and without the co
      incineration of sludges. The results show that co-incineration of sewage and
      chemical sludges does not result in an increase of toxic trace elements the total
      release in environment, with the exception of arsenic, whose total release
      increases from 1 mg t(fuel) (-1) during standard operation to 3 mg t(fuel) (-1)
      when sludges are co-incinerated. The increase of arsenic release is, however,
      attributable to the sole bottom ashes, where its concentration is five times
      higher during sludge co-incineration. No variation is observed for arsenic
      release at the stack. This fact is a further guarantee that the co-incineration
      of sludges, when performed in a state-of-the-art WTE plant, does not have
      negative effects on the atmospheric environment.

PMID- 22584267
TI  - Metals in RDF and other high calorific value fractions from mechanical treatment
      of MSW: analysis and sampling errors.
AB  - RDF and other high calorific value fractions derived from MSW by mechanical
      treatment processes contain goods such as cans, cables, zippers or batteries
      which are highly concentrated in metals. The objective of this study was to
      investigate the importance of these metal carriers (i) for total metal loads and
      (ii) for sampling errors. Six different products derived from MSW were analysed
      for carrier bound and total loads of Al, Cd, Cr, Cu, Fe, Ni, Pb and Zn.
      Sophisticated sample preparation procedures were applied in order to quantify the
      separate analyte loads from metallic carriers. Typical values for total metal
      contents and shares of carrier bound loads were found as follows: Al, 20 g kg(-1)
      (30%); Cr, 0.4 g kg(-1) (50%); Cu, 5 g kg(-1) (80%); Fe, 40 g kg(-1) (80%); Ni,
      0.15 g kg(-1) (70%); Pb, 0.4 g kg(-1) (40%); and Zn, 2 g kg(-1) (30%). NiCd
      batteries were found in three materials representing 30-70 % of total Cd contents
      (total 6-20 mg kg(-1)). Sampling errors related to the distribution of analyte
      carriers were in most cases found in the range of 50-150 % relative standard
      deviation in spite of the large sample masses of 200-800 kg. The results
      demonstrate: (1) metal carriers are responsible for significant analyte loads; if
      they are not adequately considered, total metal contents may be severely
      underestimated; (2) sampling errors are dominated by the distribution of
      carriers; (3) correct analysis of total metal contents including loads from
      metallic components requires expensive sample preparation.

PMID- 22584268
TI  - Resource management performance in Bahrain: a systematic analysis of municipal
      waste management, secondary material flows and organizational aspects.
AB  - This paper presents a detailed review of municipal solid waste (MSW) and resource
      management in Bahrain, using the recently developed UN-Habitat city profile
      methodology. Performance indicators involve quantitative assessment of waste
      collection and sweeping, controlled disposal, materials recovery and financial
      sustainability together with qualitative assessment of user and provider
      inclusivity and institutional coherence. MSW management performance in Bahrain is
      compared with data for 20 other cities. The system in Bahrain is at an
      intermediate stage of development. A waste/material flow diagram allows
      visualization of the MSW system and quantifies all inputs and outputs, with the
      vast majority of MSW deposited in a controlled, but not engineered landfill.
      International comparative analysis shows that recycling and material recovery
      rates in Bahrain (8% wt. for domestic waste, of which 3% wt. due to informal
      sector) are generally lower than other cities, whereas waste quantities and
      generation rates at 1.1 kg capita(-1) day(-1)) are relatively high. The organic
      fraction (60% wt.) is comparable to that in middle- and low-income cities (50-80%
      wt.), although on the basis of gross domestic product Bahrain is classified as a
      high-income city, for which the average is generally less than 30% wt.
      Inclusivity in waste governance is at a medium stage as not all waste system
      stakeholders are considered in decision-making. While the system now appears to
      be financially stable, key pending issues are cost-effectiveness, improving the
      standards of disposal and deployment of extensive materials recovery/recycling
      services.

PMID- 22584269
TI  - Development of a loop-mediated isothermal amplification assay for rapid detection
      of bovine parvovirus.
AB  - A loop-mediated isothermal amplification (LAMP) assay was developed for detection
      of bovine parvovirus (BPV) DNA. Four primers were designed to recognize six
      distinct regions on the target DNA based on a highly conserved sequence in the
      VP2 region of the BPV genome. The optimized LAMP reaction conditions were 8 mM
      Mg2+, 1.2 mM betaine, and an incubation at 63 degrees C for 45 min. After
      amplification the products were detected either by observing a ladder pattern
      following gel electrophoresis, observation of turbidity, or a color change with
      the addition of SYBR Green I to the reaction tube. The detection limit of the
      LAMP assay was 9 copies of BPV-DNA and was 100 times more sensitive than
      conventional PCR. A ladder pattern of bands after gel electrophoresis was
      observed for only BPV isolates and showed that the BPV LAMP assay was highly
      specific without any cross-reactivity with other related viruses. The LAMP assay
      was evaluated further using 59 field samples and the results were comparable to
      conventional PCR. The LAMP assay is a simple, rapid and economic detection
      method; it can provide a useful technique suitable for detection of BPV infection
      in both field conditions and laboratory settings.

PMID- 22584270
TI  - A high-throughput assay for HIV-1 integrase 3'-processing activity using time
      resolved fluorescence.
AB  - HIV-1 integrase (HIV-1 IN), a well-validated antiviral drug target, catalyzes
      multistep reactions to incorporate viral DNA into the genome of the host cell;
      these include both a 3'-processing (3'P) reaction and a strand transfer reaction.
      These enzymatic activities can be measured in vitro with short DNA
      oligonucleotides that mimic a single viral LTR DNA end and purified IN. A highly
      sensitive and reproducible time-resolved fluorescence (TRF)-based assay for HIV-1
      IN 3'P activity is now reported. This assay was optimized with respect to time
      and concentrations of metal ions, substrate and enzyme. The assay has now been
      used successfully to measure HIV-1 IN 3'P activity and has been shown to detect
      the anti-IN activity of several known 3'P inhibition compounds accurately. This
      assay, which is amenable to high-throughput screening, will be useful for
      identification of additional HIV-1 IN 3'P inhibitors.

PMID- 22584271
TI  - [Physical activity and tumor diseases].
AB  - Physical activity is an important health measure for many diseases but in the
      past its role in cancer control has been understudied and underappreciated. This
      chapter updates a review of physical activity and cancer risk. Overall, the
      research to date suggests that physical activity reduces the risk of developing
      some forms of cancer, helps cancer survivors cope with and recover from
      treatment, improves the long-term health of cancer survivors and possibly even
      reduces the risk of recurrence and extends survival in some cancer survivor
      groups. Much research remains to be done in this field but the compelling data
      produced so far suggests that physical activity has an important effect on the
      development of cancer and precursor stages.

PMID- 22584272
TI  - [Physical exercise as treatment of type 2 diabetes mellitus].
AB  - The beneficial role of physical exercise on glycemic control in patients with
      type 2 diabetes mellitus has been confirmed by several controlled trials
      including both aerobic and resistance exercise protocols. Exercise has been shown
      to increase insulin sensitivity, lower blood sugar levels, reduce body fat and
      improve physical fitness. Grade A scientific evidence has been assigned to the
      effect of regular physical activity on glycemic control for both endurance and
      resistance exercise.The recommendations for endurance exercise are: aerobic
      physical activity of moderate intensity (40-60% of VO(2)max or 50-70% of maximum
      heart rate) for at least 150 min/week and/or at least 90 min/week of vigorous
      aerobic exercise (> 60% of VO(2)max or > 70% of maximum heart rate). The physical
      activity should be distributed over at least 3 days/week and with no more than 2
      consecutive days without physical activity. The recommendations for resistance
      exercise are: resistance exercise should be performed at least 3 times a week,
      including all major muscle groups, progressing to 3 sets of 8-10 repetitions at a
      weight that cannot be lifted > 8-10 times.

PMID- 22584273
TI  - [A 78-year-old patient with hyperferritinemia, suspected hemochromatosis and mild
      anemia].

PMID- 22584274
TI  - Specific inherent optical quantities of complex turbid inland waters, from the
      perspective of water classification.
AB  - For optically complex turbid productive waters, the optical behavior of suspended
      particles is the keynote of characterizing the unordered variations of inherent
      optical properties (IOPs). Multiple bio-optical measurements and sampling of
      optically active substances were performed in Lake Taihu, Lake Chaohu, and Lake
      Dianchi, and Three Gorges reservoir of China, in 2008, 2009, and 2010. On the
      basis of obtaining adequate observation data, we developed an improved and robust
      water classification approach, by which complex water conditions were divided
      into three types, i.e., Type 1 (Normalized Trough Depth at 675 nm, hereafter
      NTD675, >=0.092), Type 2 (0 < NTD675 < 0.092), and Type 3 (NTD675 <= 0).
      Furthermore, the specific inherent optical quantities for suspended particles,
      including the specific absorption coefficient of non-algal particles (a*(nap)),
      the specific absorption coefficient of phytoplankton (a*(ph)), and the specific
      scattering coefficient of the suspended particles (b*(p)), were determined for
      the three classified types of waters. The validation results showed that our
      proposed values for these specific inherent optical quantities presented
      relatively high predictive accuracies, with most mean absolute percentage errors
      (MAPE) near 30%, and more importantly, performed much better than that of non
      classified waters. Additionally, relative contributions of phytoplankton and non
      algal particles to the total particulate absorption and scattering, as well as
      the spectra, were also analyzed, and the differences among the three classified
      types of waters were clarified. Overall, the results obtained in this study
      provide us with new knowledge for understanding complex varied inherent optical
      properties of highly turbid productive waters.

PMID- 22584281
TI  - Spasticity changes in SCI following a dynamic standing program using the Segway.
AB  - STUDY DESIGN: A pilot prospective pre- and post-intervention study. OBJECTIVES:
      To determine whether a dynamic standing program using the Segway Personal
      Transporter results in any measurable physiological effects in individuals with
      spinal cord injury (SCI) using both qualitative and quantitative measures of
      spasticity, pain and fatigue. SETTING: International Collaboration of Repair
      Discoveries (ICORD) Research Centre, Vancouver, BC, Canada. METHODS: Eight
      individuals with SCI ASIA (American Spinal Injury Association) A-D, who could
      stand with or without the assistance of bracing or supports, participated in a 4
      week dynamic standing program using a Segway (3 per week, 30-min sessions). The
      main outcome was spasticity as measured by the Modified Ashworth Scale (MAS).
      Secondary measures included the SCI-Spasticity Evaluation Tool, Pain Outcomes
      Questionnaire, and Fatigue Severity Scale. RESULTS: The dynamic standing sessions
      were associated with immediate improvements in spasticity (MAS) (P<0.001) and
      self-reported pain (P<0.05). Fatigue levels decreased, however this was not
      significant. There is little evidence to suggest that these beneficial outcomes
      may have lasting effects. CONCLUSIONS: Dynamic standing on the Segway may be
      effective for short-term spasticity reduction and decreased pain and fatigue.
      Future work should examine a larger sample size and help to propose mechanisms
      for potential reductions in spasticity.

PMID- 22584282
TI  - Issues influencing the decision to have upper limb surgery for people with
      tetraplegia.
AB  - STUDY DESIGN: Grounded theory. OBJECTIVES: To explore to better understand the
      decision-making process of people with tetraplegia regarding reconstructive upper
      limb (UL) surgery. SETTING: New Zealand. METHODS: In-depth interviews with 22
      people with tetraplegia, 10 of whom had UL surgery and 12 had not. Verbatim
      transcripts were analysed using constructivist grounded theory. RESULTS: The
      primary reason for having reconstructive UL surgery was to improve independence
      and return to previous pastimes. Reasons not to have surgery were hope for
      further recovery or cure, and inadequate physical environment or social supports
      while rehabilitating. In addition, women identified the temporary loss of
      independence and need for increased care while rehabilitating as issues.
      Importantly, these issues were not static, often changing in importance or
      relevance over time. CONCLUSIONS: The moment of making the decision for
      reconstructive UL surgery is elusive; therefore, multiple offers of surgery at
      different timeframes in an individual's life are required. In addition,
      flexibility in timing for surgery would allow for surgery to better coordinate
      with an individual's goals and priorities.

PMID- 22584283
TI  - Exercise participation barrier prevalence and association with exercise
      participation status in individuals with spinal cord injury.
AB  - STUDY DESIGN: Pass-code protected web survey. OBJECTIVES: Defining exercise
      participation barrier prevalence and association with exercise participation
      status in adults with spinal cord injury (SCI). SETTING: World-wide web. METHODS:
      Individuals >=18 years with ShCI in the United States completed a pass-code
      protected website survey (N=180). Odds ratios (OR) and OR 95% confidence interval
      (95% CI) assessed association between barrier presence and exercise
      participation. RESULTS: No differences existed between exercisers and non
      exercisers with respect to age, gender, injury level, injury duration, education
      level, or employment status. A larger percentage of non-exercisers reported
      household annual incomes <$7,500. The five most prevalent barriers were not
      associated with participation status (all OR 95% CI included 1). Low prevalence
      (<=13%) characterized four of the five barriers most strongly related to being a
      non-exerciser. Identifying too lazy, too difficult, or no interest as a barrier
      decreased odds of being an exerciser by 86%, 83%, and 71%, respectively. Not
      liking exercise decreased the odds of being an exerciser by 90%. CONCLUSION:
      Highly prevalent barriers were not associated with exercise participation status,
      whereas low prevalence barriers were strongly related to being a non-exerciser.
      Internal barriers had the strongest association with exercise participation
      status. The possible association between socioeconomic factors and exercise
      participation may be underappreciated. The most effective interventions to
      increase exercise participation may be multifocal approaches to enhance internal
      perceptions about and motivation to exercise, increase knowledge of how and where
      to exercise, while also reducing program and transportation financial costs.

PMID- 22584284
TI  - Life expectancy after spinal cord injury: a 50-year study.
AB  - STUDY DESIGN: Cohort of incident cases from 1955 to 2006. OBJECTIVES: To analyse
      acute and long-term mortality, estimate life expectancy and identify survival
      patterns of individuals experiencing traumatic spinal cord injury (SCI). SETTING:
      Specialised SCI unit in Australia. METHODS: Data for patients with traumatic SCI
      admitted to a spinal unit in Sydney, Australia between January 1955 and June 2006
      were collated and deaths confirmed. Cumulative survival probability was estimated
      using life-table techniques and mortality rates were calculated from the number
      of deaths and aggregate years of exposure. Standardised mortality ratios (SMRs)
      were estimated from the ratio of observed to expected number of deaths. Life
      expectancy was then estimated using adjusted attained age-specific mortality
      rates. RESULTS: From 2014 persons, 88 persons with tetraplegia (8.2%) and 38
      persons with paraplegia (4.1%) died within 12 months of injury, most often with
      complete C1-4 tetraplegia. Among first-year survivors, overall 40-year survival
      rates were 47 and 62% for persons with tetraplegia and paraplegia, respectively.
      The most significant increases in mortality were seen in those with tetraplegia
      and American Spinal Injury Association Impairment Scale (AIS) grades A-C lesions,
      with SMRs between 5.4 and 9.0 for people <50 years, reducing with advancing
      attained age. Estimated life expectancies from 25 to 65 years ranged between 69
      64%, 74-65%, 88-91% and 97-96% for C1-4 AIS A-C, C5-8 A-C, T1-S5 A-C and all AIS
      D lesions, respectively. CONCLUSION: Survival related strongly to extent of
      neurological impairment. Future research should focus on identifying contextual
      factors, personal or environmental, that may contribute to the reduced life
      expectancy after SCI.

PMID- 22584285
TI  - Demographic profile of traumatic spinal cord injuries admitted at Indian Spinal
      Injuries Centre with special emphasis on mode of injury: a retrospective study.
AB  - OBJECTIVES: To identify the demographic profile of persons with traumatic spinal
      cord injury (TSCI) admitted at the center. SETTING: Indian Spinal Injuries
      Centre. STUDY DESIGN: Retrospective analysis. METHODS: Information was collected
      in 2010 from case sheets of 1138 persons with TSCI admitted from January 2002 to
      May 2010. A telephonic survey was conducted to get further insight into fall from
      height (FFH) or road traffic accident (RTA) as a mode of injury. RESULTS: The
      mean, median and mode for the age were 34.4, 32 and 30 years, respectively.
      Male:female ratio was 5.9:1 and 63.18% (n = 719) were married. RTA was the most
      common (45%) and FFH the second most common (39.63%) mode of injury. Overall,
      66.67% suffered from paraplegia and 71.18% had complete injuries. CONCLUSION: As
      compared to other Indian published studies, our study had a much larger number of
      persons with TSCI and could be considered as the most representative amongst
      available literature for the Indian population. The study suggests that the
      demographics of spinal injury in India differs significantly from that in the
      developed countries since there was a lower mean age, much larger number of
      males, married individuals, injuries due to two wheeler accidents/falls,
      paraplegics and complete injuries. In contrast to other published Indian pilot
      studies, RTA was the most common mode of injury. Our study brings out the need
      for a proper epidemiological study and for establishing services for pre-hospital
      and acute care.

PMID- 22584286
TI  - Observations in the diagnosis of cervical myelopathy in patients suffering from
      diabetes mellitus.
AB  - OBJECTIVES: To identify any observations that could aid in the diagnosis of
      cervical myelopathy in patients suffering from diabetes mellitus (DM). We
      compared the preoperative neurological findings in patients with cervical
      myelopathy among non-diabetics, mild diabetics and severe diabetics. STUDY
      DESIGN: A retrospective comparative study. SETTING: Department of Orthopaedic
      Surgery, Wakayama Medical University, Japan. METHODS: We retrospectively reviewed
      111 patients who had undergone laminoplasty for cervical compressive myelopathy:
      56 without DM and 29 with severe diabetes more than 10 years of medication; more
      than 7.0% HbA1c; diabetic retinopathy; and delayed conduction velocity of
      peripheral nerves. For preoperative neurological assessment we compared the
      following among the three groups: the 10 s test whereby the myelopathy in the
      hand was quantified; sensory disturbance; deep tendon reflexes; Hoffmann's,
      Tromner's and Babinski's reflexes; and bladder dysfunction. RESULTS: There was no
      significant difference preoperatively in the 10 s test between the groups. Deep
      tendon reflexes were significantly decreased in group S. There were no
      significant differences in sensory disturbance and bladder dysfunction. Although
      Hoffmann's and Tromner's reflexes significantly disappeared in group S, there was
      no significant difference in positivity of Babinski's reflex between the groups.
      CONCLUSIONS: The 10 s test and Babinski's reflex are helpful for the diagnosis of
      cervical myelopathy in patients suffering from DM.

PMID- 22584287
TI  - Enormous cystic tumor of peritoneal psammocarcinoma exhibiting complete response
      to Cisplatin and cyclophosphamide after suboptimal cytoreduction: case report and
      review of the literature.
AB  - Psammocarcinoma is a serous peritoneal tumor arising from the ovary or the
      peritoneum and characterized by low-grade nuclear features, extensive psammoma
      bodies, and invasiveness. Only 62 cases have ever been documented, 30 primary
      peritoneal and 32 primary ovarian, most of which presented as small tumors.
      Adjuvant therapies, including chemotherapy and radiation, were performed in 12 of
      the primary peritoneal cases, without any clear evidence of benefit. We present a
      case of an unusually large primary peritoneal psammocarcinoma with unexpected
      outcome. The patient was a 38-year-old woman with a tumor of the peritoneum which
      adhered densely to the uterus and rectum and developed into the intra-abdominal
      cavity and retroperitoneal space. After adhesiolysis of the tumor and rectum,
      suboptimal surgical reduction left a 4 cm * 2 cm tumor segment. Postoperative
      chemotherapy, consisting of paclitaxel and carboplatin (TC) for 1 course, and
      cyclophosphamide and cisplatin (CP) for 5 courses, was conducted. The residual
      tumor responded completely to the chemotherapy and the patient is alive today,
      with no evidence of disease 15 months after the surgery. Our case implies that CP
      therapy is a potential regimen of postoperative remission-induction therapy for
      suboptimally resected primary peritoneal psammocarcinoma.

PMID- 22584288
TI  - Synthesis and electrochemical properties of substituted heteropoly acid with
      Dawson structure H7[In(H2O)P2W17O61].23H2O.
AB  - A new solid high-proton conductor, substituted heteropoly acid with Dawson
      structure H(7)[In(H(2)O)P(2)W(17)O(61)].23H(2)O, has been synthesized by the
      degradation/ion exchange/freezing method. The pH of the synthesis reaction was
      given. The product was characterized by chemical analysis, IR, UV, XRD and TG
      DTA. The determination of conductivity shows that
      H(7)[In(H(2)O)P(2)W(17)O(61)].23H(2)O is an excellent solid high-proton conductor
      with conductivity of 1.34 * 10(-3) S cm(-1) at 18  degrees C, and 70% relative
      humidity (RH). Its activation energy is 37.72 kJ mol(-1), which suggests that its
      mechanism of proton conduction is the Vehicle mechanism.

PMID- 22584289
TI  - Speech performance and sound localization abilities in Neurelec Digisonic(r) SP
      binaural cochlear implant users.
AB  - In this prospective study the outcome of the Digisonic(r) SP Binaural cochlear
      implant (CI), a device enabling electric stimulation of both cochleae by a single
      receiver, was evaluated in 14 postlingually deafened adults after 12 months of
      use. Speech perception was tested using French disyllabic words in quiet and in
      speech-shaped noise at +10 dB signal-to-noise ratio. Horizontal sound
      localization in quiet was tested using pink noise coming from 5 loudspeakers,
      from -90 to +90 degrees  along the azimuth. Speech scores in quiet were 76% (+/
      19.5 SD) in the bilateral condition, 62% (+/-24 SD) for the better ear alone and
      43.5% (+/-27 SD) for the poorer ear alone. Speech scores in noise were 60% (+/
      27.5 SD), 46% (+/-28 SD) and 28% (+/-25 SD), respectively, in the same
      conditions. Statistical analysis showed a significant advantage of the bilateral
      use in quiet and in noise (p < 0.05 compared to the better ear). Significant
      spatial perception benefits such as summation effect (p < 0.05), head shadow
      effect (p < 0.0001) and squelch effect (p < 0.0005) were noted. Sound
      localization accuracy improved significantly when using the device in the
      bilateral condition with an average root mean square of 35 degrees . Compared
      with published outcomes of usual bilateral cochlear implantation, this device
      could be a valuable alternative to two CIs. Prospective controlled trials,
      comparing the Digisonic SP Binaural CI with a standard bilateral cochlear
      implantation are mandatory to evaluate their respective advantages and cost
      effectiveness.

PMID- 22584290
TI  - Visualization of sex-dimorphic changes in the intestinal transcriptome of Fabp2
      gene-ablated mice.
AB  - BACKGROUND/AIMS: Sex differences in gene expression program have not been
      effectively explored at the transcriptome level. We aimed to develop a method for
      the analysis of transcriptome data to identify sex differences and sex-dimorphic
      responses to experimental conditions in mice. METHODS: Profiling of the small
      intestine transcriptome of chow-fed C57BL/6J (wild-type, WT) and Fabp2-/- mice
      was carried out by microarray analysis. Sex-specific and androgynous effects of
      Fabp2 gene ablation were examined using FlexArray V1.6 by comparing WT to Fabp2-/
      mice. The data generated were exported into a single spreadsheet, collated and
      transformed to identify the differentially expressed genes for pathway analysis.
      RESULTS: The method revealed enrichment of 17 sex-dimorphic pathways in the small
      intestine of WT mice compared to only 4 in Fabp2-/- mice. Comparison of the
      effects of Fabp2 loss in individual sexes revealed a male-specific upregulation
      of 5 pathways involved in the production of unsaturated fatty acids, and a female
      specific downregulation of pathways involved in xenobiotic metabolism.
      CONCLUSIONS: Our approach detected the common as well as sex-differential
      pathways that are modified due to the loss of Fabp2. These findings suggest that
      the pathways involved in nutrient and xenobiotic metabolism in the intestine are
      regulated by sex-specific mechanisms.

PMID- 22584292
TI  - Nonsteroidal anti-inflammatory drugs alter the human mesothelial pleural
      permeability via ion cellular transportation by inhibiting prostaglandin
      synthesis.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are used in clinical
      practice as analgesics or anti-inflammatory drugs. Studies have implicated them
      in participating in permeability throughout various tissues such as the kidneys
      and lungs. OBJECTIVE: The effect of NSAIDs on the pleural permeability and the
      underlying mechanisms whereby this effect is mediated were investigated. METHODS:
      Parietal pleural specimens were obtained from patients subjected to thoracic
      surgery and were mounted in Ussing chambers. Solutions containing paracetamol,
      acetylsalicylic acid, diclofenac, lornoxicam, parecoxib and ibuprofen were added
      in the chambers facing the pleural and the outer-pleural surface. Prostaglandin
      E(2) was similarly used to investigate prostaglandin synthesis involvement at low
      and high doses. Amiloride- and ouabain-pretreated specimens were used in order to
      investigate ion transportation involvement. Transmesothelial resistance (R(TM))
      was determined as a permeability indicator. RESULTS: Paracetamol, acetylsalicylic
      acid, diclofenac, lornoxicam and ibuprofen increased R(TM) on the pleural and
      outer-pleural surface, inhibited by amiloride and ouabain. Parecoxib had no
      effect on the R(TM). Prostaglandin decreased R(TM) on the pleural and outer
      pleural surface inhibited by amiloride, ouabain and ibuprofen. CONCLUSION:
      NSAIDs, except parecoxib, induce a rapid decrease of the pleural permeability by
      inhibiting cellular transportation, an effect that is mediated by prostaglandin
      synthesis inhibition.

PMID- 22584293
TI  - Ring drape do not protect against surgical site infections in colorectal surgery:
      a randomised controlled study.
AB  - INTRODUCTION: Surgical site infections (SSIs) remain a major problem in
      colorectal surgery. METHOD: In this prospective, randomised study, we compared
      two kinds of wound protection, namely, "plastic ring drape" versus "standard
      cloth towels". One hundred one patients were randomised to the control group (wet
      cloth towels) and 98 to the study cohort (ring drape). SSIs were classified
      according to Centers for Disease Control and Prevention recommendations.
      DISCUSSION: In the control group, 30 patients had an SSI, whereas 20 did so in
      the study group. This difference was not significant (p = 0.131). CONCLUSION:
      Plastic ring drape for wound protection does not guard against SSIs in colorectal
      surgery.

PMID- 22584291
TI  - Obesity and airway responsiveness: role of TNFR2.
AB  - Obese mice exhibit innate airway hyperresponsiveness (AHR), a feature of asthma.
      Tumor necrosis factor alpha (TNFalpha) is implicated in the disease progression
      and chronic inflammatory status of both obesity and asthma. TNF acts via two TNF
      receptors, TNFR1 and TNFR2. To examine the role of TNFR2 in the AHR observed in
      obese mice, we generated obese Cpe(fat) mice that were either sufficient or
      deficient in TNFR2 (Cpe(fat) and Cpe(fat)/TNFR2(-/-) mice, respectively) and
      compared them with their lean controls (WT and TNFR2(-/-) mice). Compared to WT
      mice, Cpe(fat) mice exhibited AHR to aerosolized methacholine (measured using the
      forced oscillation technique) which was ablated in Cpe(fat)/TNFR2(-/-) mice.
      Bioplex or ELISA assay indicated significant increases in serum leptin, G-CSF, IL
      7, IL-17A, TNFalpha, and KC in obese versus lean mice, as well as significant
      obesity-related increases in bronchoalveolar lavage fluid (BALF) G-CSF and IP-10,
      regardless of TNFR2 status. Importantly, BALF IL-17A was significantly increased
      over lean controls in Cpe(fat) but not Cpe(fat)/TNFR2(-/-) mice. Functional
      annotation clustering of significantly affected genes identified from microarray
      analysis comparing gene expression in lungs of Cpe(fat) and WT mice, identified
      blood vessel morphogenesis as the gene ontology category most affected by
      obesity. This category included several genes associated with AHR, including
      endothelin and trkB. Obesity increased pulmonary mRNA expression of endothelin
      and trkB in TNFR2 sufficient but not deficient mice. Our results indicate that
      TNFR2 signaling is required for the innate AHR that develops in obese mice, and
      suggest that TNFR2 may act by promoting IL-17A, endothelin, and/or trkB
      expression.

PMID- 22584294
TI  - The mRNA level of the transforming growth factor beta1 gene, but not the amount
      of the gene product, can be considered as a potential prognostic parameter in
      inflammatory bowel diseases in children.
AB  - PURPOSE: Transforming growth factor beta1 (TGF-beta1) plays a role in cell
      proliferation and differentiation, and it can modulate immune response. In this
      work, we asked whether levels of either TGF-beta1 or mRNA of the corresponding
      gene in plasma or tissue can be useful in diagnosing and/or monitoring of the
      clinical course of inflammatory bowel diseases (IBD). METHODS: The study group
      consisted of 104 pediatric patients with IBD: 36 with Crohn's disease (CD) and 68
      with ulcerative colitis (UC); 42 children represented the control group. TGF
      beta1 levels in plasma and intestinal mucosa were estimated by ELISA and
      immunohistochemistry (IHC), respectively. Levels of TGF-beta1 mRNA were
      determined by reverse transcription and real-time PCR. RESULTS: In patients with
      IBD, and in subgroups with CD and UC, no significant differences in the TGF-beta1
      level in plasma and tissue were found relative to the control group. These
      variables were not dependent on the stage of the disease, its activity or
      severity of endoscopic and histopathological findings. TGF-beta1 mRNA levels were
      significantly higher in tissue samples withdrawn during the relapse of the
      disease than in those taken during the remission or in the control group.
      However, no correlation between TGF-beta1 plasma levels and TGF-beta1 mRNA amount
      in the intestinal mucosa was observed. CONCLUSIONS: The TGF-beta1 mRNA level, but
      not the amount of the gene product, was significantly increased in the
      pathologically changed tissue during the relapse of IBD. We suggest that this
      parameter might be considered as a potential prognostic value when assessing IBD
      in children.

PMID- 22584295
TI  - The association between arteriosclerosis related diseases and diverticular
      bleeding.
AB  - PURPOSE: We previously reported that hypertension is related to colonic
      diverticular bleeding, suggesting the involvement of arteriosclerosis. The
      recurrence of diverticular bleeding has been little investigated. We aimed to
      elucidate additional risk factors for diverticular bleeding and also to
      investigate the incidence rates and risk factors for re-bleeding. METHODS:
      Between January 2006 and September 2010, 62 patients with diverticular bleeding
      were admitted to our hospital. We then selected 124 control subjects with non
      bleeding diverticula from the colonoscopy database of our department.
      Additionally, a retrospective cohort study was conducted using these case
      patients to estimate the re-bleeding rate after initial diverticular bleeding and
      the risk factors for re-bleeding. Odds ratios for diverticular bleeding were
      calculated by multivariate logistic regression in a case-control study.
      Cumulative re-bleeding rates since initial bleeding and hazard ratios of risk
      factors were estimated by Kaplan-Meier method and Cox proportional hazard model.
      RESULTS: Sixty-two patients presented 99 bleeding episodes including the initial
      ones. Diabetes mellitus (OR 2.5, 95 % CI 1.2-5.2, P = 0.03), cardio- or
      cerebrovascular diseases (OR 4.2, 95 % CI 1.7-11.3, P = 0.003), and NSAID use (OR
      3.7, 95 % CI 1.3-11.6, P = 0.02) were shown to be independent risk factors. The
      cumulative re-bleeding rates were 21 %, 34 %, and 40 % at 1, 2, and 3 years,
      respectively, in which NSAID use (HR 6.3, 95 % CI 1.7-20.7, P = 0.007) was a risk
      factor for re-bleeding. CONCLUSIONS: Diabetes mellitus and vascular diseases were
      risk factors for diverticular bleeding, suggesting systemic metabolic disorders
      and arteriosclerosis might play an important role.

PMID- 22584297
TI  - PLFA analyses of microbial communities associated with PAH-contaminated riverbank
      sediment.
AB  - Sediment contaminated with polycyclic aromatic hydrocarbons (PAHs) is widely
      distributed in aquatic ecosystems. The microbial community structure of riverbank
      PAH-contaminated sediments was investigated using phospholipid-derived fatty acid
      (PLFA) analysis. Surface and subsurface riverbank sediment was collected from a
      highly contaminated site and from an uncontaminated site along the Mahoning
      River, OH. PAH concentrations, physical sediment characteristics, and other
      microbial community parameters (biomass as phospholipid phosphate (PLP) and
      activity) were also measured. PAHs were detected in all samples but were only
      quantifiable in the contaminated (250 MUg/g g(-1)) subsurface sediment.
      Subsurface samples from both locations showed very similar PLP values and
      distribution of PLFAs, with 27-37 % of the microbial community structure being
      composed of sulfate reducing and other anaerobic bacteria. Principal components
      analysis indicated no correlation between PAH contamination and PLFA diversity.
      Although PLP and phospholipid fatty acid measurements of bacterial communities
      did not reflect the environmental differences among sites, the highly PAH
      contaminated sediment showed the highest measured microbial activity (reduction
      of 1,200 nmol INT g(-1) h(-1)), likely from a population adapted to environmental
      pollutants, rates that are much higher than measured in many uncontaminated soil
      and sediment systems. These data warrant further investigation into community
      structure at the genetic level and indicate potential for bioremediation by
      indigenous microbes.

PMID- 22584299
TI  - Missing data: a systematic review of how they are reported and handled.
AB  - BACKGROUND: The objectives of this systematic review are to examine how
      researchers report missing data in questionnaires and to provide an overview of
      current methods for dealing with missing data. METHODS: We included 262 studies
      published in 2010 in 3 leading epidemiologic journals. Information was extracted
      on how missing data were reported, types of missing, and methods for dealing with
      missing data. RESULTS: Seventy-eight percent of the studies lacked clear
      information about the measurement instruments. Missing data in multi-item
      instruments were not handled differently from other missing data. Complete-case
      analysis was most frequently reported (81% of the studies), and the selectivity
      of missing data was seldom examined. CONCLUSIONS: Although there are specific
      methods for handling missing data in item scores and in total scores of multi
      item instruments, these are seldom applied. Researchers mainly use complete-case
      analysis for both types of missing, which may seriously bias the study results.

PMID- 22584298
TI  - Impact of fungicides on the diversity and function of non-target ammonia
      oxidizing microorganisms residing in a litter soil cover.
AB  - Litter soil cover constitutes an important micro-ecosystem in sustainable
      viticulture having a key role in nutrient cycling and serving as a habitat of
      complex microbial communities. Ammonia-oxidizing bacteria (AOB) and archaea (AOA)
      are known to regulate nitrification in soil while little is known regarding their
      function and diversity in litter. We investigated the effects of two fungicides,
      penconazole and cyprodinil, commonly used in vineyards, on the function and
      diversity of total and active AOB and AOA in a microcosm study. Functional
      changes measured via potential nitrification and structural changes assessed via
      denaturating gradient gel electrophoresis (DGGE) at the DNA and RNA levels were
      contrasted with pesticide dissipation in the litter layer. The latter was
      inversely correlated with potential nitrification, which was temporarily
      inhibited at the initial sampling dates (0 to 21 days) when nearly 100 % of the
      applied pesticide amounts was still present in the litter. Fungicides induced
      changes in AOB and AOA communities with RNA-DGGE analysis showing a higher
      sensitivity. AOA were more responsive to pesticide application compared to AOB.
      Potential nitrification was less sensitive to the fungicides and was restored
      faster than structural changes, which persisted. These results support the theory
      of microbial redundancy for nitrification in a stressed litter environment.

PMID- 22584309
TI  - Key descriptors of paediatric palliative care.

PMID- 22584310
TI  - Children's palliative care:  a global concern.
AB  - Children's palliative care (CPC) is a  specialty in itself, albeit closely
      related  to adult palliative care (World Health Organization (WHO), 2002).
      However, although there are many children who require palliative care, in much of
      the world CPC has a poor profile and is inaccessible to those who need it
      (Downing et al, 2010; Knapp et al, 2011). The provision of high-quality
      palliative care for children is a global concern, with 27% of the world
      population being under the age of 15, rising to as many as 49% in countries such
      as Uganda (WHO, 2010). It has been estimated that as many as 7 million of these
      children around the world will need palliative care each year (Rushton et al,
      2002), although the true figure is likely to be higher. The public health
      approach to palliative care is key to the development of CPC services, as is the
      development of models that integrate services into existing health structures.

PMID- 22584311
TI  - Education in children's palliative care  across Europe and internationally.
AB  - Ongoing education and training is essential in health care, particularly in
      palliative care, which is still expanding both in terms of its global reach and
      its scope. Children's palliative care (CPC) is a specialty in its own right, but
      one that is still relatively new, and so appropriate and ongoing education and
      training of CPC staff is especially important. However, such education and
      training is not always accessible to those who need it, and only recently have
      significant attempts been made to quantify the extent and nature of these
      deficiencies. This paper discusses CPC education and training from a European and
      global perspective, highlighting some of the principles and challenges. It also
      looks at the recent efforts of the European Association for Palliative Care and
      the International Children's Palliative Care Network to attain a clearer picture
      of the state of global CPC education, presenting some initial findings from their
      research and discussing preliminary recommendations and future directions.

PMID- 22584312
TI  - Total pain: a reflective case study addressing the experience of  a terminally
      ill adolescent.
AB  - This article is a reflective case study of the symptom control strategies
      implemented by a hospice team caring for Jack, a teenage male with metastatic
      nasopharyngeal cancer who was experiencing severe pain. The concept of a 'total'
      approach to pain assessment and management is introduced and Jack's pain is
      analysed in the context of total pain, including the psychological, social,
      spiritual, and physical dimensions that contributed to his overall pain
      experience during his final months. This paper examines the elements of Jack's
      life that caused him anxiety and triggered pain episodes, including familial and
      cultural issues, and discusses the pharmacological and non-pharmacological
      interventions used by the hospice to address these. The article demonstrates how
      the care delivered by local services was informed by UK strategies for palliative
      and oncological care of young people.

PMID- 22584313
TI  - Respite support for children  with a life-limiting condition and  their parents:
      a literature review.
AB  - Most children with a life-limiting condition are cared for in the family home by
      their parents, who require professional support to provide this care. Owing to
      advances in medicine and medical technology these children are living longer and,
      given the often relentless and all-encompassing nature of caring for children
      with life-limiting conditions, respite (facilitation of short breaks) is
      considered central to quality palliative care provision for children and their
      families. However, there is still ambiguity in exactly what is meant by the term
      'respite', what constitutes respite care, whether the services currently provided
      meet the needs of the child and family, and how respite is best provided. This
      paper reviews the literature relating to respite as a component of children's
      palliative care. Themes from the literature are identified and discussed.
      Challenges for the providers of respite care are identified and suggestions made
      regarding the future development of responsive and family-focused respite care.

PMID- 22584314
TI  - Providing in-home palliative care  within a generalist caseload: a chance for
      nurses to reflect on life and death.
AB  - At a time when the need for in-home palliative care is on the rise, the aim of
      this interpretive phenomenological study was to understand the experiences of
      homecare nurses providing palliative care within a generalist caseload. Eight
      such nurses from one district of Quebec were interviewed. Data analysis was
      carried out according to the phenomenological method developed by Giorgi. Three
      themes emerged from the analysis: supporting the patient and his/her family,
      being concerned about providing quality care, and being confronted with death
      fosters personal development. The findings that gave rise to the first two themes
      echo similar findings from the literature, but those from which the third theme
      emerged are more novel. Important considerations for personal and professional
      development are extrapolated from these findings.

PMID- 22584315
TI  - Hospital nurses' views of the signs and symptoms that herald the onset of the
      dying phase in oncology patients.
AB  - Determining the onset of the dying phase is important, because care aims and
      interventions change once this phase begins. In the dying phase, maximising
      comfort is paramount, even if doing so causes a deterioration of cognitive
      functions. In this delicate context, it is necessary to give special attention to
      the patient's personal wishes, spiritual guidance, and rituals, and to the
      emotional support of relatives. To initiate a care plan for the dying, health
      professionals must recognise and acknowledge when a patient enters the dying
      phase. This article describes hospital nurses' perspectives on the signs and
      symptoms that herald the onset of the dying phase in oncology patients, obtained
      via three focus group discussions. A broad range of signs and symptoms were
      reported and are presented here as a conceptual model. Further research is needed
      to determine whether the signs and symptoms that mark the onset of the dying
      phase in oncology patients may be tumour-specific.

PMID- 22584317
TI  - [Hepatocarcinogenesis in NASH].
AB  - With the increase of lifestyle-related diseases, metabolic syndrome has clearly
      increased in recent years. Fatty liver, which is the manifestation of metabolic
      syndrome in the liver, has received little attention because it is not the actual
      cause of death. However, with the developing increase of metabolic syndrome, non
      alcoholic fatty liver disease(NAFLD), especially nonalcoholic
      steatohepatits(NASH), has increased, and has received much attention. In chronic
      liver disease, liver cirrhosis develops, finally leading to liver failure. The
      most serious chronic liver disease is progression to liver cancer. Once hepatic
      fibrosis develops, the hepatic carcinogenic rate has been increased. Hepatic
      carcinogenic rate has been reported to reach 8%per year in hepatitis type C
      related liver cirrhosis. Although little has been reported about NASH-related
      liver cancer, NASH-related hepatic carcinogenic rate reached to about 2. 6%per
      year. In this review, we will describe the epidemiology, gender differences, risk
      factors and pathogenesis of NASH-related liver cancer.

PMID- 22584318
TI  - [Induction chemotherapy followed by chemoradiotherapy for the patients with far
      advanced nasopharyngeal carcinoma - our treatment strategy].
AB  - Nasopharyngeal carcinoma(NPC)is a rare malignant neoplasm arising from the head
      and neck region that affects less than 1 per 100, 000 in the Japanese population.
      NPC is a highly radiosensitive and chemosensitive cancer when compared to other
      head and neck cancers. Its treatment has mainly been developed by using
      radiotherapy and chemotherapy, rather than surgery. The standard of care now
      calls for radiotherapy alone for early-stage patients, and chemoradiotherapy for
      the advanced stages. Despite its sensitivity to treatments, survival rates of
      patients with Stage IV A, IV B, N 2/3 have been inadequate. The effectiveness of
      triplet-regimen induction chemotherapy for patients with locally advanced head
      and neck cancer has recently been reported. Since 2009, we have tried to improve
      survival by treating patients with triplet-regimen induction chemotherapy
      consisting of docetaxel, cisplatin and S-1, followed by cisplatin-based
      chemoradiotherapy. This treatment strategy has dramatically improved both overall
      survival and the complete response rate. Although it is a very promising
      treatment, it is highly toxic at the same time. We have experienced more than a
      few hematological and non-hematological grade 3/4 toxicities. Therefore, when
      conducting a treatment, considering its indication and building a sufficient back
      up system are very important.

PMID- 22584319
TI  - [Chemotherapy for thymic carcinoma].
AB  - Thymic epithelial neoplasm is a quite rare malignancy arising from the thymic
      epithelium, and comprises thymoma, thymic carcinoma, and thymic neuroendocrine
      carcinoma. The incidence of thymic carcinoma and neuroendocrine carcinoma is much
      less than thymoma, accounting for 1-4%of anterior mediastinal tumors. These rare
      tumors are called"orphan tumors,"and standards of clinical management(including
      chemotherapeutic regimens)have not yet been determined for them yet because of
      their rarity. In the advanced setting, palliative-intent chemotherapy has been
      applied using cisplatin-based triplet or quartet chemotherapy with second
      generation antitumor drugs, with reference to chemotherapeutic regimens for
      invasive thymoma such as ADOC, CAP, and VIP chemotherapy. However, biological
      plausibility is lacking for this approach, given that these tumors differ from
      thymoma in their expression of cellular surface proteins such as c-Kit and
      epidermal growth factor receptors. While limited to thymic carcinoma, platinum
      doublet chemotherapy with a third-generation antitumor drug as first-line
      chemotherapy is anticipated to offer the same clinical efficacy as multiple-agent
      combination chemotherapy, but with less toxicities. In second-line or later-lines
      of chemotherapy, single-agent chemotherapy may be optimal. Molecular biological
      approaches have been under investigation, but molecular targeted agents remain
      unavailable.

PMID- 22584320
TI  - [Medical treatment for gastrointestinal stromal tumor (GIST) in Japan].
AB  - To facilitate an optimal diagnosis and treatment of GIST in Japan, the Japanese
      Clinical Practice Guideline for GIST was proposed by the GIST Guideline
      Subcommittee. Multidisciplinary treatment planning is needed(involving
      pathologists, radiologists, surgeons and medical oncologists)for patients with
      GIST. Medical treatment is usually selected for unresectable GIST, metastatic
      GIST at the initial examination, and recurrent GIST. Imatinib is strongly
      recommended for patients with KIT-positive GIST; the standard dose of imatinib
      mesylate(Glivec)is 400 mg/day. For patients with imatinib-resistant GIST,
      Sunitinib (Sutent)is now approved in Japan and is covered by medical insurance.
      However, high-dose imatinib(>400mg/day)has not yet been approved in Japan.

PMID- 22584321
TI  - [Chemoradiotherapy for anal squamous cell carcinoma].
AB  - In the guidelines on American National Comprehensive Cancer Network, local
      excision with adequate margin is recommended as a primary treatment for patients
      with T1, N0, and well-differentiated anal margin cancers. Otherwise, concurrent
      chemotherapy using mitomycin C(10mg/m2, day 1 and 29)and 5-FU(1,000mg/m2/day,
      continuous intravenous infusion, day 1-4 and 29-32)with radiation(total dose of
      45-59 Gy)is the recommended primary treatment for all other stages of
      nonmetastatic anal margin and anal canal cancer. Abdominoperineal resection is
      performed for patients with local recurrent diseases or residual tumor after
      chemoradiotherapy. Chemotherapy, using cisplatin(100mg/m2, day 2)and 5
      FU(1,000mg/m2/day, day 1-5)every four weeks, is recommended for patients with
      distant metastases, and radiotherapy can also be given for the local control of
      symptomatic anal lesions. Abdominoperineal resection has been performed in Japan;
      however, use of chemoradiotherapy is expected to increase for patients with anal
      squamous cell carcinoma. Clarification of the correct positioning of
      chemoradiotherapy using cisplatin, and the development of treatment using oral
      anticancer agents, are expected in the future by a clinical trial now in
      progress.

PMID- 22584322
TI  - [The chemotherapy of peritoneal malignant mesothelioma].
AB  - Peritoneal malignant mesothelioma is a rare disorder with a poor prognosis, and a
      standard treatment for it has not yet been established. Therefore, treatment of
      this disorder tends to be selected according to pleura malignant mesothelioma. We
      analyzed case reports in Japan. The median survival time(MST)with this disease
      was 12 months and the 1-year survival rate was 47. 3% in the chemotherapy group.
      It was found through a case-series study that platinum pharmaceutical plus
      antimetabolite are effective against peritoneal malignant mesothelioma. A
      gemcitabine(GEM)plus cisplatin(CDDP)regimen had been selected as a conventional
      treatment, but subsequently, pemetrexed(MTA)was covered by health insurance for
      pleural malignant mesothelioma in 2007, and the MTA plus CDDP regimen became the
      standard treatment. However, a phase III trial of GEM plus CDDP regimen and MTA
      plus CDDP regimen was not performed. There is a need to perform these phase III
      trials in the future. In our institution, the MTA plus CDDP regimen was the first
      line treatment, and the GEM plus CDDP regimen was the second-line treatment
      against peritoneal malignant mesothelioma. Palonosetron hydrochloride and
      aprepitant should be used actively in treatment. Also, carboplatin(CBDCA)is
      effective as an alternative therapy of the CDDP against renal disorder case, but
      hematotoxicity requires attention.

PMID- 22584323
TI  - [Chemotherapy and hormone therapy for uterine sarcomas].
AB  - Uterine sarcomas are relatively rare mesenchymal malignant neoplasms with poor
      prognosis, accounting for 8%of all uterine malignant neoplasms. There are only a
      few moderately active cytotoxic agents for this entity, and therefore,
      chemotherapy for uterine sarcomas is palliative in most cases. According to
      traditional classification systems, uterine sarcomas encompass
      carcinosarcoma(CS), leiomyosarcoma(LMS), and endometrial stromal cell
      sarcoma(ESS). For carcinosarcoma, ifosfamide, cisplatin, and paclitaxel are
      reported to be moderately effective single agents. The combination of ifosfamide
      and cisplatin appeared to improve progression-free survival, but the severe
      toxicity it induced was not negligible. Paclitaxel and ifosfamide were the only
      chemotherapy regimen which slightly improved both progression-free and overall
      survival. For leiomyosarcoma and undifferentiated endometrial sarcoma(formerly
      named high-grade ESS), doxorubicin, ifosfamide, and gemcitabine are moderately
      effective single agents. There are several reports showing the effectiveness of
      gemcitabine plus docetaxel. For endometrial stromal sarcoma(formerly named low
      grade ESS), progestins and aromatase inhibitors have been proven beneficial.

PMID- 22584324
TI  - [Treatment of patients with cancer of an unknown primary site].
AB  - Cancer of unknown primary(CUP)is a heterogenous group of tumors that accounts for
      3 to 5 percent of all malignancies. Due to CUP's heterogeneity, clinical trials
      are difficult to perform and articles published on the disease require careful
      interpretation. Among CUP's, there are several clinical groups that are treated
      with specific treatment modalities. Each clinical group has similar treatment
      effects and prognoses with common malignancies that arise in adjacent locations,
      such as breast cancer and head/neck cancer. Therefore, accurate histological
      diagnosis and careful clinical staging are important. However, many CUP's do not
      belong to these specific clinical groups and generally have a poor prognosis. The
      treatment is usually directed based upon histology, location of the tumor, and
      stage. Platinum agents, taxanes and other new cytotoxic drugs are often used for
      systemic therapy, but their efficacy is often limited. Currently, specific
      molecular markers and targeted therapy are being explored.

PMID- 22584325
TI  - [Docetaxel in combination with epirubicin as the first-line chemotherapy for
      advanced and recurrent breast cancer: a multicenter phase II study].
AB  - This study examined the efficacy and tolerability of docetaxel(DOC)in combination
      with epirubicin(EPI)as the first-line treatment for patients with advanced and
      recurrent breast cancer. A total of 56 female patients with metastatic breast
      cancer not previously treated for metastatic disease received DOC(60mg/m2)and
      EPI(60mg/m2)on day 1 every 3 weeks. The patient characteristics included a median
      age of 53 years. Advanced disease was present in 86% of patients, and recurrent
      disease was found in 14%; 3 or more metastatic sites had been diagnosed in 38% of
      patients, and 59% patients were ER+. The median number of courses administered
      was 6. The median dose intensity was 18. 7mg/m2week for DOC and EPI, and the
      relative dose intensities were 93. 5%and 93. 3%, respectively. The clinical
      responses included a complete response in 5%, a partial response in 54%, and
      stable disease in 33% of patients, with a disease control rate of 92%. The
      progression-free survival was 78. 3%, and the overall survival was 91. 9% at 1
      year. Grade 3/4 toxicities included neutropenia in 82%, leukopenia in 71%,
      febrile neutropenia in 16%, anorexia in 9%, and anemia in 7%of the patients.
      Neither congestive heart failure nor toxic death occurred. The D and E
      combination with doses of 60mg/m2 is an active and generally well-tolerated
      regimen that can be used as first-line chemotherapy for patients with metastatic
      breast cancer.

PMID- 22584326
TI  - [Efficacy of high-dose toremifene as a second-line hormone therapy in patients
      with advanced or metastatic breast cancer resistant to aromatase inhibitor].
AB  - BACKGROUND: Aromatase inhibitors(AIs)are frequently employed for advanced or
      metastatic postmenopausal breast cancer as first-line hormone therapy. However,
      it is unknown which hormonal agent is the most appropriate after AI has failed.
      PATIENTS AND METHODS: Five hormone-responsive postmenopausal women who used AI as
      a first-line hormone therapy for advanced or metastatic breast cancer, but AI
      failed, received high-dose toremifene therapy(HD-TOR: 120mg/day)in our hospital.
      Efficacy and safety were evaluated. RESULTS: Patients were all-hormone sensitive,
      and only one case had HER2 overexpression. All patients had received
      anastrozole(ANA)as first-line hormone therapy. Of a total of 5 cases, 3 were
      evaluated as partial responses(PR), 1 was a long stable disease(L-SD), and 1 was
      a progressive disease(PD). The overall response rate (RR)was 60. 0%(3/5 cases)and
      the clinical benefit rate(CB)was 80. 0%(4/5 cases). Grade 1 dry mouth was
      observed in one case as an adverse event. CONCLUSIONS: HD-TOR as a second-line
      therapy is optimal for advanced or metastatic AI resistance postmenopausal breast
      cancer.

PMID- 22584327
TI  - [Laryngeal preservation for hypopharyngeal cancer by radiotherapy with S-1 and
      vitamin A(TAR therapy)].
AB  - The objective of this study was to analyze the outcome of hypopharyngeal cancer
      patients who underwent triple combination treatment with S-1, vitamin A and
      radiation(TAR therapy), and to analyze the role of TAR therapy for treating
      locally advanced hypopharyngeal cancer patients. 146 patients(stage I: 10 cases,
      stage II : 22 cases, stage III : 23 cases, stage IV: 91 cases)with hypopharyngeal
      squamous cell carcinoma were treated with TAR therapy(S-1; orally, 65mg/m2day,
      twice a day; vitamin A(retinol palmitate): 50, 000 I U/day, intra-musculary on
      each day of radiation; radiation: 1. 5-2 Gy/day, 5 days/week). Histologic
      complete responders at 30-40 Gy continued TAR therapy up to 60-70 Gy.
      Nonresponders at 30-40 Gy underwent surgery. The overall 5-year survival and
      disease-specific 5-year survival rates were 50. 5%and 59%respectively. The
      cumulative 3-year laryngeal preservation rate for stage I was 100%, 82. 5% for
      stage II, 66. 6% for stage III, and 35%for stage IV. Laryngeal preservation was
      fair in T1/T2 patients(81%), but not satisfactory in T3/T4 patients(21. 4%). S- 1
      is administered orally, and TAR therapy can be conducted in the clinic with low
      toxicity. However, protocols with high intensity may be necessary to improve
      laryngeal preservation for locally advanced(T4)hypopharyngeal cancer.

PMID- 22584328
TI  - [Efficacy and safety of low-dose matrix-type transdermal fentanyl applied for
      opioid initiation].
AB  - Minimum-size matrix-type transdermal fentanyl(TDF)(Durotep(r)MTPatch 2.1mg), with
      a dose equivalent to half of a minimum-size conventional-type TDF(Durotep Patch
      2.5mg), was newly produced. Now, the use of minimum-size matrix-type TDF at the
      early stage of opioid initiation has become possible. For several reasons, we
      sometimes encounter clinical cases where clinicians are inclined to use the
      minimum-size matrix-type TDF first without prior use of other opioids. In order
      to evaluate the efficacy and safety of minimum-size matrix-type TDF, we analyzed
      49 patients, retrospectively for whom minimum-size matrix-type TDF was initiated.
      We used the Wong-Baker faces pain rating scale to assess the effect of matrix
      type TDF. The rate of effective and ineffective cases were 55% and 37%,
      respectively, and 8% of cases could not be evaluated. The frequency of side
      effects such as nausea, somnolence, sense of fatigue and constipation was 20%,
      16%, 4% and 2%, respectively. However, respiration depression was not documented
      at all. The score of the palliative prognostic index was significantly higher in
      ineffective cases compared with effective cases. Patients who were judged
      ineffective tended to have poor prognoses. One of the reasons matrix-type TDF was
      thought to be ineffective in such patients was that a rapid increase of the dose
      according to dynamic changes of symptoms was difficult. These findings suggest
      that we can use a matrix-type TDF as opioid initiation relatively safely, but in
      cases with poor prognoses, we should use it under appropriate and sufficient
      rescue setting only when other opioids cannot be prescribed.

PMID- 22584329
TI  - [Retrospective study on intravenous compound injection of cancer pain patients
      with oxycodone and hydrocotarnine preparation in comparison with subcutaneous
      administration].
AB  - In Japan, although oral oxycodone is widely used for cancer pain treatment, there
      is no injection preparation of oxycodone used as a single ingredient. Only the
      compound injection of oxycodone and hydrocotarnine has received approval.
      Subcutaneous administration of the drug is approved, but there are few efficacy
      and safety reports about its intravenous administration. We compared 245
      patients(187 intravenous administration patients and, 58 subcutaneous
      administration patients)to whom the compound injection of oxycodone and
      hydrocotarnine was administered from April, 2008 to September, 2011, in order to
      investigate the drug's efficacy and safety. The reasons for injection were the
      impossibility of oral administration in 105 patients, a need for dose adjustment
      in 56 patients, and that other drugs were not as effective in 37 patients, and
      side effect reduction in 33 patients. The average change in the numeric rating
      scale(0-10)was 3. 7->1. 8 in intravenous administration, and 3. 4->1. 2 in
      subcutaneous administration. The incidence of main adverse events(intravenous
      administration/subcutaneous administration)were constipation(37%/28%),
      vomiting(31%/34%), and somnolence(52%/50%). There was no significant difference
      in efficacy and safety. The conversion ratio differed in a case due to a change,
      and about 20 to 40% of addition was needed within four days after the start. It
      is considered that compound injection of oxycodone and hydrocotarnine is
      effective for cancer pain treatment.

PMID- 22584330
TI  - [Promising new injection method to prevent angialgia/phlebitis from epirubicin
      hydrochloride therapy for breast cancer].
AB  - Epirubicin hydrochloride(EPI)is well known to cause phlebitis as a typical
      adverse drug reaction. By preventing the development of severe phlebitis,
      patients are expected to continue effective chemotherapy with EPI without a
      decrease in QOL. We have previously reported promising results of a new injection
      method to prevent phlebitis from occurring during EPI therapy thorough a
      prospective clinical trial in our hospital(Jpn J Cancer Chemother 36: 969-974,
      2009). In the present study, we have compared the conventional injection
      method(EPI main -route method, n=15)with our new method, which has been
      consistently practiced at present(EPI sub -route method, n=77). We found that in
      the EPI main -route method, angialgia/phlebitis developed in 14 of 15 cases(Grade
      3, 53. 3%), leading to alteration of the regimen in 3 cases. On the other hand,
      with the EPI sub -route method, incidence of angialgia/phlebitis was markedly
      decreased, and only 6 of 77 cases developed these adverse reactions(Grade 3, 0%).
      One possible explanation for these results is that the reduction of intimal
      stimulation by the EPI sub -route method might be caused by the dilution and
      washout of EPI with pre-medication, as well as the shortened infusion times of
      EPI. Therefore, on the basis of the above hypothesis, we conclude that the EPI
      sub-route method might be a more effective treatment for the expected prevention
      of angialgia/phlebitis.

PMID- 22584331
TI  - [Side effect analyses in consideration of renal functions for capecitabine
      administered patients].
AB  - There is a high frequency of serious side effects overseas in cases with a
      reduced creatinine clearance, for whom a 75% reduction in dose administration is
      recommended. The insidence of hematological toxicity was investigated in 89
      cases[L group: Ccr<5 0mL/min(6 cases), M group: 50mL/min<=Ccr<80mL/min(34 cases),
      and H group: 80mL/min<=Ccr(49 cases)]who took capecitabine alone. The frequency
      of side effects was significantly high in group L[L: 6 cases(100%), M: 30
      cases(88. 2%), and H: 30 cases(61. 2%)]. The frequency of grade 2 or more was
      higher in cases with a reduced renal function[L: 5 cases(83. 3%),M: 17 cases(50.
      0%), and H: 18 cases(36. 7%)]. A significantly high decrease in hemoglobin was
      seen in group L[all grades; L: 5 cases(83. 3%),M: 20 cases(58. 8%), and H: 12
      cases(24. 5%), and a grade 2 or more; L: 5 cases (83. 3%), M: 7 cases(20. 6%),
      and H: 5 cases (10. 2%)]. Moreover, there was little improvement when a decrease
      in hemoglobin occurred in grade 3 cases. Our findings suggest that it is
      necessary to manage drug dosage for Japanese patients while considering their
      renal function, and to actively monitor for any side effects.

PMID- 22584332
TI  - [Analysis of risk factors of drug-induced lung injury in patients receiving
      gemcitabine treatment].
AB  - Gemcitabine hydrochloride is a very safe medicine that even outpatients can be
      administered, and the bone marrow depression that is the dose limiting factor
      remains moderate and does not need special treatment, although it is confirmed in
      most cases. Meanwhile, caution is required because there is a possibility of drug
      induced lung injury and death due to high frequency, compared with the appearance
      rate described in the packaging insertion. We investigated the clinical
      background of a patient in whom drug-induced lung injury appeared, and clarified
      the risk factor by administering gemcitabine hydrochloride. Males, people aged 65
      or over, those with a smoking history and those undergoing first-line
      chemotherapy treatment are at risk of drug-induced lung injury. Attention must be
      paid to the occurrence of drug-induced lung injury, to examining the clinical
      course, the chest image, and the blood test, and to do earlier detection, the
      offending medicine discontinuance, and beginning of the treatment.

PMID- 22584333
TI  - [Long-term survival of patient with brain metastases from lung cancer treated by
      pemetrexed monotherapy].
AB  - A 61-year-old female was diagnosed with cT2N1M0 adenocarcinoma in the right lung.
      Following resection of the right middle lobe and dissection of the second group
      of lymph nodes in July 2007, she was found to have pN2 disease, and carboplatin
      plus paclitaxel was administered as postoperative chemotherapy. Recurrence was
      found and gefitinib was administered as first-line chemotherapy. While the
      patient was followed on an outpatient basis, dysgeusia and headache developed in
      March 2009. As multiple brain metastases were confirmed by contrast-enhanced
      computed tomography, cranial irradiation (30 Gy in 10 fractions)was administered.
      Upon improvement of the patient's status to a level treatable by chemotherapy, a
      new second-line chemotherapy with pemetrexed was started. Since then, the patient
      has been followed on an outpatient basis and has currently completed 21 courses
      of chemotherapy. No recurrence has been observed thus far. The results suggest
      that pemetrexed is an effective agent for the treatment of brain metastases from
      lung adenocarcinoma.

PMID- 22584334
TI  - [Rapid multidisciplinary therapy for an advanced lung cancer patient with severe
      tracheal stenosis resulting in long-term survival].
AB  - A 61-year-old female was admitted to our hospital due to dyspnea and facial
      edema. A chest CT scan showed stenosis of the trachea and superior vena cava due
      to a tumor around the trachea. She underwent partial resection of the tracheal
      tumor via a rigid bronchoscope introduced into the trachea, and placement of a
      Dumon Y-stent. Undifferentiated non-small cell lung cancer was diagnosed. After
      airway management, she underwent cisplatin-based chemoradiotherapy and total 56
      Gy stereotactic radiotherapy for the tumor. The tumor size was reduced by 40%
      immediately after chemoradiotherapy. Six months after the tracheal stent
      insertion, bone metastases were pointed out, and we changed the chemotherapy
      regimen to gefitinib. She has been in good condition without tumor growth for
      more than six years after tracheal stent insertion.

PMID- 22584335
TI  - [Case report - cytoreductive surgery combined with perioperative intraperitoneal
      chemotherapy for pseudomyxoma peritonei complicated with long-term persisting
      intestinal pneumonitis].
AB  - A 62-year-old woman had suffered from interstitial pneumonitis caused by collagen
      disease and had received steroids and immunosuppressants for twenty years. She
      was diagnosed as pseudomyxoma peritonei by CT examination and underwent
      palliative cytoreduction two years ago, but peritoneal relapse occurred one year
      later. At her first visit to our office, she complained of abdominal distension
      and respiratory distress of Hugh-Jones classification 2-3. CT showed interstitial
      pneumonitis and a massive intra-abdominal mucinous tumor. Complete  cytoreduction
      by peritonectomy procedures, combined with intraperitoneal chemotherapy with 50
      mg of cisplatin, was performed. The duration of the operation was 860 minutes and
      the blood loss was 7, 000 mL. Postoperative steroidal replacement was performed
      and neither acute exacerbation of interstitial pneumonitis nor any other severe
      complication occurred. Today, in the 3-year follow-up period, she is doing well
      without any sign of recurrence of pseudomyxoma peritonei.

PMID- 22584336
TI  - [Once-weekly bortezomib plus dexamethasone therapy induced complete response,
      reducing severe gastrointestinal adverse events for a patient with relapsed
      multiple myeloma - a case report].
AB  - A 74-year-old female with relapsed multiple myeloma was treated with twice-weekly
      bortezomib plus dexamethasone (BD)therapy, but severe gastrointestinal adverse
      events(grade 3 paralytic ileus and constipation)developed. After changing to once
      weekly BD therapy, >= grade 3 gastrointestinal adverse events did not develop,
      and she was able to continue BD therapy. A complete response and a treatment-free
      interval >= 2 years were obtained by 8 courses of BD therapy. This case report
      suggests that once-weekly BD therapy may reduce severe gastrointestinal adverse
      events without decreasing the clinical efficacy for multiple myeloma.

PMID- 22584337
TI  - [A case of neurotoxicity reduced with pregabalin in R-CHOP chemotherapy for
      diffuse large B-cell lymphoma].
AB  - When performing R-CHOP(rituximab, cyclophosphamide, doxorubicin, vincristine, and
      prednisone)for diffuse large B-cell lymphoma(DLBCL), neurotoxicity of
      vincristine(VCR)is the serious dose-limiting factor.Pregabalin is one of the
      first-line treatments for painful diabetic peripheral neuropathy in many
      countries, and we have administered it to relieve the neurotoxicity associated
      with adverse effects of VCR in a DLBCL patient treated with the R-CHOP regimen.A
      49-year-old man with kidney DLBCL had surgery performed.Afterward, the R-CHOP
      regimen was introduced.In order to relieve the neurotoxicity of VCR, pregabalin
      was used from day 8 in the second course.The severity of sensory neurotoxicity
      after the administration of pregabalin was improved from CTCAE(v4.0)grade 3 to
      grade 1.Therefore, there is a possibility that VCR-induced neurotoxicity is
      relieved by pregabalin.Further trials are needed to confirm the value of
      pregabalin.

PMID- 22584338
TI  - [A case of disseminated carcinomatosis of bone marrow treated by S-1 and
      cisplatin after distal gastrectomy for early gastric cancer].
AB  - Patients with bone metastasis originating from gastric cancer experience
      complications from DIC. They are treated with anticoagulation therapy or platelet
      transfusion, but their prognosis is poor. Our case was a 50-year-old male who had
      undergone distal gastrectomy for early gastric cancer[pT1a(M)N0M0, pStage I a]ten
      years previously. He was admitted to our hospital complaining of backache. As a
      result of his examination, he was diagnosed with disseminated carcinosis of bone
      marrow with DIC as a postoperative recurrence of gastric cancer. The patient was
      treated with combination chemotherapy of S-1 and cisplatin(S-1 80 mg/body, po,
      day 1-21 and cisplatin 50mg/body, iv, day 8). After one course of treatment, DIC
      was resolved and his pain was relieved. He survived for about nine months. S-1
      and cisplatin are considered to be effective for disseminated carcinosis of bone
      marrow.

PMID- 22584339
TI  - [A case of an advanced gastric cancer patient on hemodialysis achieving long-term
      progression-free survival after CPT-11+CDDP therapy].
AB  - A 59-year-old male with chronic kidney disease was diagnosed as having advanced
      gastric cancer(cT2N1P0H1M0), and CPT-11+CDDP therapy was started for him
      simultaneously with hemodialysis(HD). Serum CDDP concentrations were measured in
      the 1st course, and free-platinum(f-Pt)showing the anti-tumor effect was found to
      be eliminated by HD. Serum f-Pt levels, however, re-elevated until 24 hours after
      HD completion. Serum concentrations measured in the 15th course showed that f-Pt
      levels became higher than those observed in the 1st course, suggesting that CDDP
      was not completely removed by HD. Medical treatment was continued until the liver
      metastases were judged to be a progression disease at completion of the 18th
      course. When CDDP was administered to patients on HD, it was necessary to pay
      attention to various CDDP serum concentrations, and to tailor the dose to a
      tolerable level in each patient. Such an individual therapy might enable CPT
      11+CDDP therapy to be one of the medical treatments of choice for advanced
      gastric cancer patients on HD.

PMID- 22584340
TI  - [A case study of advanced gastric cancer patient treated with S
      1+paclitaxel/lentinan].
AB  - A 47 -year-old male presented with gastric cancer, with right cervical and para
      aortic lymph node metastases. The patient had not undergone a curative operation,
      but was treated with immunochemotherapy in combination with S-1 60 mg/m2(2 weeks
      administration and 2 weeks rest), paclitaxel 60 mg/m2(day 1, 8, 15), and Lentinan
      2mg/body(day 1, 8, 15). After 3 courses of this treatment, no hot-spots were
      identified on cervical and para-aorta lymph nodes by PET-CT examination. We
      decided to perform total gastrectomy with D3 lymphadenectomy and Roux-en Y
      reconstruction. On histopathological examination, no malignancy was seen in the
      lymph nodes and the main tumor was judged to be grade 2. With this combined
      immunochemotherapy, the patient had a favorable outcome without side effects,
      which proved effective for far advanced gastric cancer.

PMID- 22584341
TI  - [A case of advanced gastric cancer found to be remaining by gastrectomy after a
      clinically complete response to chemotherapy].
AB  - The patient was a 72-year-old woman diagnosed with advanced gastric cancer,
      hepatic portal lymph node and para-aortic lymph node metastases. After five
      courses of S-1/CDDP combination therapy, both the primary tumor and lymph node
      metastases disappeared clinically. She wished to continue chemotherapy instead of
      having a resection. After three more courses of S-1/CDDP therapy, gastric cancer
      and lymph node metastases were still completely regressed, but complications of
      carcinoma of the gallbladder were suspected. Gastrectomy was performed with
      cholecystectomy, and a histopathological examination revealed cancer cells
      remaining in the gastric submucosa and xanthogranulomatous cholecystitis. We
      consider surgical therapy for clinically completely disappearing advanced gastric
      cancer by chemotherapy, in addition to case report.

PMID- 22584342
TI  - [A case of gastric cancer with rhabdoid features showing better prognosis through
      S-1/CDDP chemotherapy].
AB  - Although gastric cancers(GCs)with rhabdoid features are rare, they are known to
      show a poorer prognosis compared with conventional GCs. Indeed, more than half of
      reported GCs with rhabdoid features died within 6 months after receiving any kind
      of initial treatment. Obviously, no effective chemotherapy has been reported. In
      this study, we present a case of GC with rhabdoid features which showed a better
      response to a chemotherapy, S-1/CDDP, and lived for over 12 months after the
      initial chemotherapy. A 75-year-old man was seen in our hospital for
      epigastralgia. Detailed examinations revealed that he had GC at Stage IV.
      Consequently, he underwent S-1/CDDP treatment. This treatment produced a good
      response for 6 months, minimizing the size of the primary tumor and eradicating
      distant metastases. Re-growth of the primary tumor without uprising distant
      metastasis was confirmed 8 months after the initialS -1/CDDP treatment, and the
      patient went through a gastrectomy for curative care. After surgery, a precise
      pathological examination revealed that the primary tumor possessed a poorly
      differentiated adenocarcinoma that contained tumor cells with typical rhabdoid
      features. In the end, the patient died of liver metastasis 13 months after the
      initial S-1/CDDP chemotherapy.

PMID- 22584343
TI  - [A case of primary adenocarcinoma of small intestine responding to XELOX
      chemotherapy and leading to a partial metabolic response].
AB  - We report a case of adenocarcinoma of the small intestine responding to XELOX
      chemotherapy, leading to a partial metabolic response(PMR). The patient was a 58
      year-old male with multiple peritoneal dissemination of adenocarcinoma of the
      small intestine. Chemotherapy with XELOX(L-OHP 130 mg/m2 on day 1 , and
      capecitabine 1,000 mg/m2 on days 1-14)was performed. After 4 courses, a
      significant tumor reduction was obtained. This case suggests that chemotherapy
      with XELOX is a potential regimen for small intestinal adenocarcinoma.

PMID- 22584344
TI  - [A case of long survival after resection and treatment with imatinib mesylate
      against metachronous liver metastases and a lung metastasis of a small intestine
      gastrointestinal stromal tumor].
AB  - A 68-year-old man was admitted to our hospital because of an abdominal tumor.
      Computed tomography(CT)showed a 6 cm tumor in the abdominal cavity. Surgery was
      performed. Upon laparotomy, a 6 cm tumor was found at the small intestine (210
      cm)on the anal side from the Treitz ligament. A partial resection of the small
      intestine was performed. Immunohistochemistry showed positive staining for c-kit,
      and the diagnosis of gastrointestinal stromal tumor was confirmed. Multiple liver
      metastases and a lung metastasis were observed over the next 2 years. We started
      chemotherapy with imatinib mesylate at a dose of 400mg/day. The size of the
      tumors was unchanged, and no new lesion was observed. The patient has been alive
      and well as of 6 years after the initial operation.

PMID- 22584345
TI  - [Two cases of hyperammonemic patients treated by chemotherapy for colorectal
      cancer].
AB  - We report two patients having hyperammonemic encephalopathy while being treated
      with chemotherapy for colorectal cancer. The first patient was a 69-year-old man
      with sigmoid colon cancer, having a massive invasion to the urinary bladder. He
      received SOX therapy following a pelvic exenteration operation. After the third
      course of SOX therapy, he presented with general fatigue and repeated seizures,
      and blood examination showed a high level of serum ammonium. He was diagnosed as
      hyperammonemic encephalopathy. The second patients was a 60-year-old woman with
      ascending colon cancer and liver metastasis having portal vein tumor thrombosis,
      who was given a palliative resection of ascending colon, and then underwent
      modified FOLFOX6 therapy. At the second course, she fell into a deep coma, and
      blood examination revealed a high level of serum ammonium. In both patients,
      treatment with infusion of branched-chain amino acid solutions resolved the
      symptoms of encephalopathy. Acute neurotoxicity caused by hyperammonemic
      encephalopathy during chemotherapy for colorectal cancer is rare and not well
      recognized, but it is a clinically important complication. We should pay more
      attention to hyperammonemic encephalopathy of patients receiving chemotherapy for
      colorectal cancer.

PMID- 22584346
TI  - [A case of remnant liver metastases after resection of liver metastases from
      rectal cancer following treatment with 5-FU, L-OHP and CPT-11, with markedly
      effective treatment by cetuximab plus S-1].
AB  - FOLFOX or FOLFIRI are commonly used as first- or second-line chemotherapy for
      unresectable colorectal cancer or its metastases.Recently, it had become a trend
      to add bevacizumab or cetuximab(Cmab)limited to the K-ras wild-type or
      panitumumab(Pmab)limited to the K-ras wild-type.At the present time, a common
      third-line chemotherapy is CPT-11 plus Cmab limited to the K-ras wild-type, or
      Cmab/Pmab.However, the results are unsatisfactory.With Cmab plus S-1 we treated a
      case of remnant liver metastases from rectal cancer which was a K-ras wild-type,
      after treating 5-FU, L-OHP and CPT-11. The tumor marker dropped and 7 focuses of
      liver metastases disappeared after 6 courses of treatment(complete response: CR
      in)and CR was achieved after 9 courses treatment.After 10 courses of treatment, a
      new lesion appeared on S5 of the liver and we performed percutaneous
      radiofrequency ablation.

PMID- 22584347
TI  - [Two cases of CPT-11 and CDDP chemotherapy for advanced pancreatic cancer].
AB  - We report two cases of advanced pancreatic cancer treated with CPT-11 and CDDP as
      third-line chemotherapy. CPT-11 was administered as an intravenous injection at a
      dose of 60 mg/m2, and CDDP was administered at a dose of 30 mg/m2 biweekly. The
      patients showed no adverse events greater than grade 2 toxicity, and these
      adverse events were tolerated. The patients showed partial response and stable
      disease. These results suggested that this treatment schedule was safe and
      effective for progressive pancreatic cancer.

PMID- 22584348
TI  - 18F-fluorodeoxyglucose PET/CT findings in pleural effusions of patients with
      known cancer. A cytopathological correlation.
AB  - AIM: Pleural effusion is common in cancer patients and to determine its malignant
      origin is of huge clinical significance. PET/CT with 18F-FDG is of diagnostic
      value in staging and follow-up, but its ability to differentiate between
      malignant and benign effusions is not precisely known. PATIENTS, METHODS: We
      examined 50 PET/CT from 47 patients (29 men, 18 women, 60 +/- 16 years) with
      pleural effusion and known cancer (24 NSCLC, 7 lymphomas, 5 breasts, 4 GIST, 3
      mesotheliomas, 2 head and neck, 2 malignant teratoma, 1 colorectal, 1
      oesophageal, 1 melanoma) for FDG uptake in the effusions using SUV(max). This was
      correlated to cytopathology performed after a median of 21 days (interquartile
      range -3 to 23), which included pH, relative distribution (macrophages,
      neutrophils, eosinophils, basophils, lymphocytes, plasmocytes), and absolute cell
      count. RESULTS: Malignant cells were found in 17 effusions (34%) (6 NSCLC, 5
      lymphomas, 2 breasts, 2 mesotheliomas, 2 malignant teratomas). SUV in malignant
      effusions were higher than in benign ones [3.7 (95%CI 1.8-5.6) vs. 1.7 g/ml (1.5
      1.9), p = 0.001], with a correlation between malignant effusion and SUV (Spearman
      coefficient r = 0.50, p = 0.001), but not with other cytopathological or
      radiological parameters (ROC area 0.83 +/- 0.06). Using a 2.2-mg/l SUV threshold,
      12 PET/CT studies were positive and 38 negative with sensitivity, specificity,
      positive and negative predictive values of 53%, 91%, 75% and 79%, respectively.
      For NSCLC only (n = 24), ROC area was 0.95 +/- 0.04, 7 studies were positive and
      17 negative with a sensitivity, specificity, positive and negative predictive
      values of 83%, 89%, 71 and 94%, respectively. CONCLUSION: PET/CT may help to
      differentiate the malignant or benign origin of a pleural effusion with a high
      specificity in patients with known cancer, in particular NSCLC.

PMID- 22584350
TI  - Inhibition of herpes simplex virus infection by oligomeric stilbenoids through
      ROS generation.
AB  - Stilbenoids including resveratrol contain the basic structural unit of 1,2
      diphenylethylene. Naturally occurring stilbenoids have broad structural features
      due to oligomerization and modifications and some have demonstrated potent
      biological activities. In an effort to identify bioactive stilbenoids, we
      screened a group of dimeric and oligomeric stilbenoids against HSV-1 and HSV-2
      infection. Several trimeric and tetrameric derivatives showed anti-herpetic
      activity at single digit micromolar concentrations. HSV-1 and HSV-2 replication
      requires for NF-kappaB and MAPK activation. The compounds showed no inhibitory
      activity against NF-kappaB and Erk/MAPK activation, instead those compounds
      promoted rapid and transient release of reactive oxygen species (ROS). Addition
      of N-acetylcysteine (NAC), a scavenger of ROS, reversed the inhibitory effect of
      those compounds against HSV replication. In addition to the identification of
      resveratrol derivatives with potent anti-HSV activity, our results uncover a
      mechanism of polyphenol-mediated anti-HSV response, linking anti-herpetic
      activity of oligomeric stilbenoids to innate immunity.

PMID- 22584351
TI  - IFN-lambda inhibits HIV-1 integration and post-transcriptional events in vitro,
      but there is only limited in vivo repression of viral production.
AB  - The lambda interferons (IL-28a, 28b, and IL-29) inhibit the replication of many
      viruses, but their role in the inhibition of HIV-1 infection remains unclear.
      During this study, we monitored IL-29 production in HIV-1 infected individuals
      and analyzed the in vitro and in vivo inhibition of HIV-1 production. Prior
      treatment with IL-28a or IL-29 induced an antiviral state in cultured primary T
      cells, which suppressed HIV-1 integration and post-transcriptional events. The
      antiviral factors MxA, OAS, and PKR were up-regulated. In HIV-1 infected
      patients, IL-29 level was increased along with the depletion of CD4+ T-cells in
      peripheral blood, while the elevated IL-29 did not show a significantly negative
      correlation with viral load. Further analysis of HIV-1 infected individuals
      showed that IL-29 was positively correlated with IFN-beta and anti-inflammatory
      cytokine IL-10, and was negatively correlated with IFN-gamma, which might suggest
      that IFN-lambda participates in modulating antiviral immune responses during HIV
      1 infection in vivo. Together, although IFN-lambda impeded HIV-1 infection of T
      cells in vitro, IFN-lambda showed only limited in vivo repression of viral
      production. The modulation of IFN-lambda on inflammatory factors might be worthy
      for further concentrating on for better understanding the host immune response
      during HIV-1 infection.

PMID- 22584352
TI  - In vitro antiviral activity of dehydroepiandrosterone, 17 synthetic analogs and
      ERK modulators against herpes simplex virus type 1.
AB  - In the present study the in vitro antiviral activity of dehydroepiandrosterone
      (DHEA) and 17 synthetic derivatives against herpes simplex type 1 (HSV-1) was
      determined. DHEA, epiandrosterone (EA), two synthetic DHEA analogs and three
      synthetic EA analogs showed a selective inhibitory effect on HSV in vitro
      multiplication. DHEA and E2, a synthetic derivative of EA, were not found to be
      virucidal to cell-free HSV-1 and did not impair virus adsorption or penetration.
      We determined that treatment with both compounds decreased viral protein
      synthesis. Moreover, inhibitory effect of DHEA and E2 on extracellular viral
      titer was stronger than the inhibition found on total viral infectivity,
      suggesting that the antiherpetic activity of these compounds may also be in part
      due to an inhibition in virus formation and release. Since DHEA is a known
      Raf/MEK/ERK signaling pathway activator, we studied the role of this pathway on
      HSV-1 infection. ERK1/2 phosphorylation was stimulated in HSV-1 infected
      cultures. UO126, a Raf/MEK/ERK signaling pathway inhibitor, impaired viral
      multiplication, while anisomycin, an activator of this pathway, enhanced it.
      Treatment with DHEA 6 h before infection enhanced HSV-1 multiplication. On the
      contrary, pre-treatment with E2, which does not modulate Raf/MEK/ERK signaling
      pathway, did not produce an increase of viral replication. Taking together these
      results, the antiviral activity of DHEA seems to occur via a mechanism
      independent of its ability to modulate ERK phosphorylation.

PMID- 22584354
TI  - The changing hypothesis of the gut. The intestinal microbiome is increasingly
      seen as vital to human health.

PMID- 22584353
TI  - Pharmacoeconomic impact of different regimens to prevent cytomegalovirus
      infection in renal transplant recipients.
AB  - BACKGROUND: The aim of this study was to determine the cost impact of four
      different strategies for prevention of cytomegalovirus (CMV) disease after renal
      transplantation. METHODS: Hospitalization data and medical resource utilization
      data were prospectively collected alongside two randomized trials. In the first
      trial, the patients were randomized to 3-month prophylaxis with either oral
      ganciclovir (1 g t.i.d., n = 36) or valacyclovir (2 g q.i.d., n = 35), and to the
      control group (n = 12) managed by deferred therapy. In the second trial, the
      patients were randomly assigned to 3-month valacyclovir prophylaxis (n = 34) or
      preemptive therapy with valganciclovir (900 mg b.i.d. for a minimum of 14 days, n
      = 36) for significant CMV DNAemia. The cost analysis involved all real costs
      directly related to CMV during the first year after renal transplantation.
      RESULTS: The mean CMV-associated costs per patient were EUR 4,581, 2,577, 4,968,
      and 8,050 in patients in the ganciclovir, valacyclovir, preemptive, and deferred
      therapy groups, respectively (p < 0.001). Valacyclovir prophylaxis was
      significantly less expensive than any other regimen. The cost of one episode of
      CMV disease was EUR 7,510 per patient. Due to excessive incidence of CMV disease,
      deferred therapy was the most expensive strategy (p < 0.001). CONCLUSIONS:
      Valacyclovir prophylaxis is less expensive strategy compared with any other
      regimen.

PMID- 22584357
TI  - Response to "The anglerfish deception".

PMID- 22584356
TI  - The effects of artificial gender imbalance. Science & Society Series on Sex and
      Science.

PMID- 22584359
TI  - Expression profiles of a MhCTR1 gene in relation to banana fruit ripening.
AB  - The banana (Musa spp.) is a typical climacteric fruit of high economic
      importance. The development of bananas from maturing to ripening is characterized
      by increased ethylene production accompanied by a respiration burst. To elucidate
      the signal transduction pathway involved in the ethylene regulation of banana
      ripening, a gene homologous to Arabidopsis CTR1 (constitutive triple response 1)
      was isolated from Musa spp. (Hsien Jin Chiao, AAA group) and designated as
      MhCTR1. MhCTR1 spans 11.5 kilobases and consists of 15 exons and 14 introns with
      consensus GT-AG nucleotides situated at their boundaries. MhCTR1 encodes a
      polypeptide of 805 amino acid residues with a calculated molecular weight of 88.6
      kDa. The deduced amino acid sequence of MhCTR1 demonstrates 55%, 56% and 55%
      homology to AtCTR1, RhCTR1, and LeCTR1, respectively. MhCTR1 is expressed mostly
      in the mature green pulp and root organs. During fruit development MhCTR1
      expression increases just before ethylene production rises. Moreover, MhCTR1
      expression was detected mainly in the pulps at ripening stage 3, and correlated
      with the onset of peel yellowing, while MhCTR1 was constitutively expressed in
      the peels. MhCTR1 expression could be induced by ethylene treatment (0.01 MUL L(
      1)), and MhCTR1 expression decreased in both peel and pulp 24 h after treatment.
      Overall, changes observed in MhCTR1 expression in the pulp closely related to the
      regulation of the banana ripening process.

PMID- 22584362
TI  - Why quality improvement initiatives succeed or fail: the MUSIQ of quality
      improvement.

PMID- 22584361
TI  - Sunitinib-induced autoimmune thyroiditis in a patient with metastatic renal cell
      carcinoma: a case report.
AB  - Sunitinib is an oral multitargeted tyrosine kinase inhibitor that was newly
      approved by the FDA for the treatment of renal cell carcinoma and imatinib
      resistant gastrointestinal stromal tumors. Although generally well tolerated,
      common side effects of sunitinib have been reported, with an important and well
      recognized example being hypothyroidism. Although the exact mechanism of
      sunitinib-induced hypothyroidism is unclear, some authors have suggested
      sunitinib might induce hypothyroidism by the blockade of iodine uptake,
      destructive thyroiditis and inhibition of peroxidase activity. In these studies
      autoimmune-mediated hypothyroidism could not be demonstrated as an etiological
      factor. We herein report the case of a 71-year-old woman diagnosed as metastatic
      renal cell carcinoma with severe autoimmune hypothyroidism associated with
      sunitinib after 10 months of treatment. To the best of our knowledge, this is the
      first report that shows sunitinib may induce autoimmune thyroiditis. Further
      clinical and experimental studies with larger patient groups are required to
      verify the findings of the present study. Routine monitoring of thyroid
      autoantibodies including antithyroglobulin and antithyroid peroxidase antibodies
      and thyroid ultrasonography are recommended during the treatment of sunitinib
      induced hypothyroidism.

PMID- 22584363
TI  - Group counselling improves quality for patients with limited health literacy.
AB  - BACKGROUND: The North County Health Centre in Reston, Virginia, recently enhanced
      the quality and accessibility of physician-coordinated behavioural counselling.
      METHODS: A patient survey confirmed that the clinic could improve behaviour
      change support. Physician time constraints, practice productivity issues and
      treatment priorities were identified barriers to systems change. Systems changes
      included teamwork, group visits, community engagement and trusted online consumer
      resources. Validated statistical process control (SPC) techniques evaluated
      variation in monthly 90-minute group visits for Spanish- and English-speaking
      patients during which we reviewed evidence-based recommendations, hosted
      community speakers and held brief individual encounters using encounter forms
      with built-in motivational interviewing techniques. RESULTS: On average, four
      English-speaking patients attended, with 42% of the participants who attended
      more than one meeting successfully achieving their self-reported goal. On
      average, nine Spanish-speaking patients attended, with eight (86%) of the
      participants achieving their goals. Documentation of recorded prevention
      counselling improved from 15% to 67%. Patients indicated that they found that
      what they learned is transferable to their everyday 1ives. CONCLUSION: The total
      number of patient encounters in a clinical session did not dramatically change.
      Language preference was not a hurdle. Teamwork among patients, providers, staff
      and community members was a key to success. Group visits improved the amount of
      prevention counselling and helped patients with limited health literacy achieve
      their prevention goals.

PMID- 22584364
TI  - Primary healthcare response to family violence: a Delphi evaluation tool.
AB  - BACKGROUND: Family violence is identified as a significant yet preventable public
      health problem internationally and in Aotearoa, New Zealand. Despite this,
      responses to family violence within New Zealand primary healthcare settings are
      generally limited and ad hoc. Along with guidelines and resources, a systems
      approach is indicated to support a safe and effective response to those who
      experience violence in the home. AIM: To modify an existing United States
      evaluation tool to guide implementation of family violence intervention
      programmes within New Zealand primary healthcare. METHODS: Twenty-nine expert
      panelists, representing diverse family violence prevention and intervention
      organisations across New Zealand, participated in three rounds of a modified
      Delphi method to identify ideal primary healthcare family violence response
      programme indicators. In Round One, tool scope and context issues for New Zealand
      were identified; in Round Two, expert panelists identified ideal indicators and
      rated indicator importance, and in Round Three, expert panelists attended a one
      day workshop to achieve consensus on tool categories, indicators, scoring and
      measurement notes. The developed tool was subsequently piloted at six volunteer
      primary healthcare sites for performance, clarity and usefulness. RESULTS: The
      final tool encompasses 143 indicators organised within 10 categories. Pilot sites
      found the tool and evaluation experience useful in guiding programme development.
      CONCLUSION: The evaluation tool represents a best practice standard enabling
      focused family violence intervention programme development and quality
      improvement within primary healthcare settings. A standardised evaluation tool
      may be useful in guiding programme development. Future evaluations will enable
      individual and national benchmarking activities, using category, overall and
      target scores to measure progress across settings and over time.

PMID- 22584365
TI  - Resilience and smoking: the implications for general practitioners and other
      primary healthcare practitioners.
AB  - BACKGROUND: Smoking cessation counselling is a key component of medical treatment
      and health promotion activities performed by general practitioners (GPs);
      however, GPs are often left wondering why their patients continue to smoke in
      spite of being given information about the  damaging health effects and medical
      treatments. The concept of resilience to smoking is an emerging idea that offers
      an innovative perspective to smoking cessation. AIMS: To understand why some
      people continue to smoke in spite of well-known adverse health effects, what and
      how  resilience factors impact on people's smoking, and the role and limitations
      of the GP in fostering resilience to smoking. METHOD: A qualitative study of 22
      oral-history interviews was conducted in Adelaide, South Australia. Interviews
      were audio-recorded, transcribed and analysed  for emergent themes. RESULTS: The
      main themes of most relevance to GPs are the resilience to health messages,
      resilience factors associated with smoking abstinence and the common pathways
      that lead to successful smoking cessation. DISCUSSION: Understanding smoking and 
      resilience can assist the GP to provide more effective and supportive smoking
      cessation assistance. The GP may assist in the process by fostering the adoption
      of resilience factors, much of which is already part of routine GP work but may
      not yet be considered part of a holistic smoking cessation  strategy. Through
      this holistic approach, smoking cessation is likely to be just one of many
      physical and social benefits, and avoids victim blaming. Broad system change to
      increase the levels of resilience within individuals and communities may then
      mean that smokers can stop more easily  with brief interventions. Such changes
      are beyond the limits of a single GP, but provide opportunities to lobby
      government for future public health programmes aimed at promoting both the
      internal traits and external resources that are required for resilience building.

PMID- 22584366
TI  - Referral Writer: preliminary evidence for the value of comprehensive referral
      letters.
AB  - BACKGROUND: We aimed to explore if increasing the amount of relevant information
      relayed in referral letters between general practitioners (GPs) or family
      physicians and hospital specialists helps in the scheduling of appointments for
      patients. We report a before and after study  comparing outcomes before and after
      the introduction of software to assist referral writing. METHODS: The
      participants were GPs and hospital specialists based in metropolitan Perth,
      Western Australia. The amount of relevant information in referral letters from
      GPs was assessed with  reference to a published schedule three months before and
      four months after deploying interactive computerised Referral Writer software
      (RW). The longer period after deploying the RW was to allow GPs time to become
      familiar with the RW. The letters were scored by a researcher for the amount  of
      relevant information included and then independently assessed by two specialists
      in each of six specialties to determine if they were able to decide which
      patients needed to be seen soonest and what was the most likely outcome of the
      specialist consultation. The actual diagnosis for each  case was recorded later
      to assess if there was an association between the amount of relevant information
      relayed and the diagnosis of life limiting or other pathologies. RESULTS: Each GP
      referred 5.6 patients on average, range (1, 14) before the RW and 4.8 patients,
      range (0, 14)  after the RW. The amount of relevant information in the letters
      improved substantially after the RW, mean difference 37%, 95% Confidence Interval
      43-30%, P <0.001. For 91% of letters after the RW, both specialists in each
      specialty were confident or very confident that they  had enough information to
      decide when the patient should come to their clinic; this had increased from 50%
      before the RW, P = 0.001. There was no association observed between the amount of
      relevant information relayed and the final diagnosis. CONCLUSION: Standardising
      and  using electronic communications to refer appears to facilitate rational
      scheduling of specialist appointments. Comprehensive referral may help to ensure
      that the right patients are seen by the specialist sooner rather than later.

PMID- 22584367
TI  - NICE and the Quality and Outcomes Framework (QOF) 2009-2011.
AB  - The National Institute for Health and Clinical Excellence (NICE) has been
      responsible for managing the process of developing new clinical and health
      improvement indicators for the United Kingdom (UK) Quality and Outcomes Framework
      (QOF) and reviewing the current QOF clinical indicator  set since April 2009.
      This paper sets out in detail the NICE-led process for QOF indicator development
      and describes experience to date (2009-2011) in four key areas: prioritisation of
      clinical guideline recommendations by the QOF advisory committee, development and
      piloting of quality  indicators, cost-effectiveness analysis and retirement of
      QOF indicators. It concludes by reflecting on potential future developments of
      the QOF.

PMID- 22584368
TI  - Increasing the general level of academic capacity in general practice:
      introducing mandatory research training for general practitioner trainees through
      a participatory research process.
AB  - BACKGROUND: To obtain good quality evidence-based clinical work there needs to be
      a culture of critical appraisal, and strong bridges between the clinical and the
      academic worlds in general practice. AIM: The aim was to educate the general
      practitioner (GP) trainees  to obtain critical appraisal skills, and through the
      development and implementation of the mandatory programme to gradually empower
      the GP community to achieve academic capacity by creating a link between the GP
      researchers and the GP training community. This was done by developing a faculty,
      giving teaching skills to GP academics, and research skills to GP clinicians;
      and creating an awareness of the potential benefits of critical appraisal in
      training GP surgeries. METHODS: Development and implementation of a faculty and a
      programme through a participatory action research-inspired  project, with process
      evaluation from the beginning of the planning phase. RESULTS: From 2006 to 2009,
      we built a teaching faculty of 25 teachers among clinical GPs and GP academics;
      developed the training programme; and delivered the programme to 95 GP trainees.
      Some of the GP  trainees later showed an interest in more substantial research
      projects, and GP trainers with no previous association with the research
      environment started to show an interest through their function as GP trainers.
      The GP academics of the faculty, however, felt that it was difficult to continue 
      the engagement because of the still increasing demand for published knowledge
      production in academia. CONCLUSION: It is possible to support the development of
      general academic capacity in general practice using participatory design in
      collaboration with GP academics and clinicians,  building bridges between
      academia and clinical work, as well as within academia between research
      publication and teaching. There is, however, a generic barrier in the regulation
      of academia itself.

PMID- 22584369
TI  - Evaluation of the methodological quality of the Health Protection Agency's 2009
      guidance on neuraminidase inhibitors.
AB  - BACKGROUND: The Health Protection Agency (HPA) issued guidance advocating the
      prescription of neuraminidase inhibitors in July 2009 in response to a predicted
      pandemic of influenza. Although the contents of the guidance have been debated,
      the methodology has not. METHOD: The guidance was evaluated by two reviewers
      using a validated and internationally recognised tool for assessing guidelines,
      the Appraisal of Guidelines Research & Evaluation instrument (AGREE). This tool
      scores six domains independently of each other. RESULTS: The guidance scored  61%
      for the domain scope and purpose and 54% for the domain clarity and presentation.
      By contrast, it scored only 31% for rigour of development due to poor linkage of
      its recommendations to evidence. CONCLUSION: The HPA should improve its
      performance in this domain to general practitioners  in order to improve the
      credibility of its future guidance.

PMID- 22584370
TI  - A comparison of embedded total task instruction in teaching behavioral chains to
      massed one-on-one instruction for students with intellectual disabilities:
      accessing general education settings and core academic content.
AB  - This study is a comparison of the embedded instruction of behavioral chains with
      more traditional (one-on-one massed trials in special education setting)
      instructional procedures for teaching behavioral chains to students with
      significant cognitive disabilities. Although embedded instruction has emerged as
      a promising potential instructional procedure, no literature has examined the
      efficacy of embedded instructional procedures to teach more complex chained
      behaviors. To date, all research on embedding instruction in general education
      settings has focused on teaching discrete skills. This study compares instruction
      of embedded total task chains with more traditional (one-on-one massed trials in
      special education setting) instructional procedures for teaching behavioral
      chains. The chains targeted for instruction were selected by state core
      educational needs and functional skill development.

PMID- 22584371
TI  - Topical dexamethasone for recurrent aphthous ulceration reduces pain and size and
      increases healing with no significant adverse events.

PMID- 22584372
TI  - There's an app for that: content analysis of paid health and fitness apps.
AB  - BACKGROUND: The introduction of Apple's iPhone provided a platform for developers
      to design third-party apps, which greatly expanded the functionality and utility
      of mobile devices for public health. OBJECTIVE: This study provides an overview
      of the developers' written descriptions of health and fitness apps and appraises
      each app's potential for influencing behavior change. METHODS: Data for this
      study came from a content analysis of health and fitness app descriptions
      available on iTunes during February 2011. The Health Education Curriculum
      Analysis Tool (HECAT) and the Precede-Proceed Model (PPM) were used as frameworks
      to guide the coding of 3336 paid apps. RESULTS: Compared to apps with a cost less
      than US $0.99, apps exceeding US $0.99 were more likely to be scored as intending
      to promote health or prevent disease (92.55%, 1925/3336 vs 83.59%, 1411/3336;
      P<.001), to be credible or trustworthy (91.11%, 1895/3336 vs 86.14%, 1454/3349;
      P<.001), and more likely to be used personally or recommended to a health care
      client (72.93%, 1517/2644 vs 66.77%, 1127/2644; P<.001). Apps related to healthy
      eating, physical activity, and personal health and wellness were more common than
      apps for substance abuse, mental and emotional health, violence prevention and
      safety, and sexual and reproductive health. Reinforcing apps were less common
      than predisposing and enabling apps. Only 1.86% (62/3336) of apps included all 3
      factors (ie, predisposing, enabling, and reinforcing). CONCLUSIONS: Development
      efforts could target public health behaviors for which few apps currently exist.
      Furthermore, practitioners should be cautious when promoting the use of apps as
      it appears most provide health-related information (predisposing) or make
      attempts at enabling behavior, with almost none including all theoretical factors
      recommended for behavior change.

PMID- 22584373
TI  - Synthesis and characterization of novel S,N and Se,N homodimetallic Ag(I)
      complexes.
AB  - Novel C2-symmetric doubly bidentate Se,N and S,N-ligands based on a readily
      available Troger's base backbone were synthesized and fully characterized. Their
      coordination properties were studied in dinuclear Ag(I)-complexes employing (1)H,
      (77)Se and (1)H-(15)N HETCOR NMR spectroscopy as well as X-ray diffraction
      crystallography. In solution, a single ligand can accommodate two silver atoms by
      coordination to nitrogen and sulfur or selenium. The investigations in the solid
      state revealed the presence of a pentacoordinated silver atom (NSO(3) and
      N(3)Se(2) donor sets are influenced by the solvent employed during the
      crystallization). In the solid state, the Ag(I)-complex with the S,N-ligand 2b
      forms dimeric structures bridged by the two perchlorate counterions. The
      analogous Se,N-ligand 2c coordinates to Ag(I) and forms polymeric
      enantiomerically pure helices, although the crystal is racemic.

PMID- 22584375
TI  - Endoplasmic reticulum stress and neurodegeneration in experimental cerebral
      malaria.
AB  - Experimental cerebral malaria (ECM) resulting from Plasmodium berghei ANKA (PbA)
      infection in mice results in neuronal cell death. However, the precise mechanisms
      leading to neuronal cell death in ECM have not been fully elucidated. In the
      present study, we report the presence of endoplasmic reticulum (ER) stress
      markers and activation of the unfolded protein response (UPR) in the brain during
      the pathogenesis of ECM. Specific findings included activation of PKR-like
      ERkinase, inositol-requiring enzyme 1 and cleavage of activating transcription
      factor (ATF) 6 indicating the activation of all three major arms of the UPR.
      Further, we found changes in the protein levels of phosphorylated eukaryotic
      initiation factor alpha (p-eIF2alpha), ATF4, growth arrest and DNA damage
      inducible protein 34, B cell lymphoma protein 2 (BCL-2), BCL-2-associated X
      protein, caspase-7, cleavage of caspase-3, and caspase-12. Our results
      demonstrate that ER stress-induced neuronal cell death in PbA-infected mice is
      associated with the expression of the pro-apoptotic molecule CHOP and
      downregulation of anti-apoptotic ER quality control molecules binding
      immunoglobulin protein, calreticulin and calnexin. Further CHOP was found to be
      localized in neurons and plays an essential role in neuronal cell death as
      revealed by our Fluoro-Jade B double staining. These results implicate an
      imbalance between ER stress-mediated pro-apoptotic and anti-apoptotic/survival
      signalling as a critical determinant of neuronal cell death in ECM.

PMID- 22584377
TI  - Acanthocephalans in northern fur seals (Callorhinus ursinus) and a harbor seal
      (Phoca vitulina) on St. Paul Island, Alaska: species, prevalence, and
      biodiversity in four fur seal subpopulations.
AB  - Monitoring studies of acanthocephalans in northern fur seals (Callorhinus ursinus
      Linnaeus, 1758) (NFSs) and a harbor seal (Phoca vitulina Linnaeus, 1758) were
      performed on St. Paul Island, Alaska, in July-August 2011. Gastrointestinal
      tracts of 105 humanely harvested NFS subadult males (SAMs) (3-4 years old) were
      collected during the annual Aleut subsistence harvest at four haul-out areas
      (HOAS): Lukanin (n = 26 NFSs), Polovina (n = 28), Gorbatch (n = 30), and
      Morzhovyi (n = 21). One gastrointestinal tract collected from a harbor seal
      (about 3-4 years old) found dead at Morzhovyi HOAS was also examined. The total
      prevalence of infection in NFSs with acanthocephalans was 29.52 % with variations
      from 7.69 % to 47.62 % between the four different HOAS. Eight acanthocephalan
      species of two genera-Corynosoma Luhe, 1904 (Corynosoma strumosum, Corynosoma
      alaskensis, Corynosoma cameroni, Corynosoma semerme, Corynosoma similis,
      Corynosoma validum, and Corynosoma villosum), and Bolbosoma Porta, 1908
      (Bolbosoma nipponicum)-were found in the NFSs and a harbor seal. This is a new
      record of C. alaskensis for the NFSs. Short biological notes of the species found
      are presented. Differences in species composition as well as in prevalence of
      acanthocephalans parasitizing NFSs were observed in subpopulations from four
      different HOAS on St. Paul Island. The highest biodiversity of acanthocephalans
      and infection were found in subpopulations on Polovina and Morzhovyj HOAS, the
      lowest was on Lukanin HOAS. From 3.2 % (for C. validum) to 19.4 % (for C.
      villosum) of NFSs were infected by one acanthocephalan species; two species were
      found in 22.6 %; three in 9.7 %; and four in 3.2 %. Further studies of NFS
      parasites are necessary to follow the trends in parasitic infection rates and
      diversity in NFS population on the Pribilov Islands and for monitoring the
      influence of various ecological factors on NFS populations in Alaska.

PMID- 22584374
TI  - The reciprocal relationship between primordial germ cells and pluripotent stem
      cells.
AB  - Primordial germ cells (PGCs) are induced in the epiblast early in mammalian
      development. They develop their specific fate separate from somatic cells by the
      generation of a unique transcriptional profile and by epigenetic modifications of
      histones and DNA. PGCs are related to pluripotent cells in many respects, both on
      a molecular and a cell biological level. Mimicking their in vivo development,
      PGCs can be derived in culture from pluripotent cells. Vice versa, PGCs can be
      converted in vitro into pluripotent embryonic germ cells. Recent evidence
      indicates that the derivation of pluripotent embryonic stem cells from explanted
      inner cell mass cells may pass through a germ cell-like state, but that this
      intermediate is not obligatory. In this review, we discuss PGC development and
      its relevance to pluripotency in mammalian embryos. We outline possibilities and
      problems connected to the application of in vitro-derived germ cells in
      reproductive medicine.

PMID- 22584378
TI  - Inhibitory effect of Ferula asafoetida L. (Umbelliferae) on Blastocystis sp.
      subtype 3 growth in vitro.
AB  - Asafoetida is an oleo-gum-resin obtained from many Ferula species and frequently
      used in traditional medicine. The current study aimed to evaluate the activity of
      asafoetida against the in vitro growth of Blastocystis sp. Asafoetida as powder
      form (Ap) and oil-form (Ao) extracts at concentrations of 2, 4, 8, 16, and 20
      mg/ml and 5, 10, 25, 40, and 50 mg/ml, respectively were incubated with isolates
      of Blastocystis sp. subtype 3 for 24, 72, and 144 h and compared to the reference
      antiprotozoan drug metronidazole at concentrations of 10, 100, and 500 MUg/ml.
      Asafoetida either as Ap or Ao decreased counts and viability of all tested
      isolates of Blastocystis sp. subtype 3 which was confirmed by microscopy. The
      degree of the inhibitory effect was dependent on the concentration, form, as well
      as the time of incubation with asafoetida extracts. The lowest concentrations of
      Ap and Ao that caused complete (100 %) inhibition of Blastocystis growth and
      highest (100 %) percentage inhibition of multiplication was 16 and 40 mg/ml,
      respectively; mean counts at these concentrations either did not differ or
      decreased significantly when compared to metronidazole control (p < 0.05). Also,
      the parasites did not resume growth after re-cultivation in asafoetida-free
      medium when examined further after 48, 72, and 144 h of cultivation. These
      findings demonstrate the potential of phytomedicine asafoetida as a potent
      natural alternative for treatment of Blastocystis sp.infection.

PMID- 22584380
TI  - Validity of a questionnaire to assess the physical activity level in coronary
      artery disease patients.
AB  - The aim of the study is to compare, in coronary artery disease patients, physical
      activity (PA) assessed with the Dijon Physical Activity Questionnaire (DPAQ) and
      the true PA objectively measured using an accelerometer. Seventy patients wore an
      accelerometer (MyWellness Key actimeter) throughout 1 week after a cardiac
      rehabilitation program that included therapeutic education about regular PA.
      Patients completed the DPAQ at the end of the week. The mean weekly active energy
      expenditure was 619.9 +/- 374.6 kcal, and the mean DPAQ score was 21.3 +/- 3.1/30
      points. There were low but significant correlations between total active energy
      expenditure and the DPAQ score (rho=0.4, P=0.009). There were no correlations
      between peak power output and total DPAQ score. The DPAQ significantly correlates
      with objective measures given by the MyWellness Key actimeter. The choice between
      these tools relies on the clinician's appreciation, taking into account patients'
      characteristics and goals as well as the cost of the method and availability of
      the tool.

PMID- 22584379
TI  - Proteomic analysis of salivary glands of female Anopheles barbirostris species A2
      (Diptera: Culicidae) by two-dimensional gel electrophoresis and mass
      spectrometry.
AB  - Salivary gland proteins of adult female Anopheles barbirostris species A2, a
      potential vector of Plasmodium vivax in Thailand, were analyzed using a proteomic
      approach (two-dimensional gel electrophoresis followed by nanoLC-MS). Two
      dimensional gel electrophoresis revealed approximately 75 well-resolved spots on
      the reference gel. Most of the protein spots displayed relative molecular masses
      from 14 to 85 kDa and isoelectric points ranging from 3.9 to 10. The proteome
      profiles of A. barbirostris species A2 female salivary glands were affected by
      aging. The typical electrophoretic pattern of the female salivary glands was
      reached in 48 h post emergence, suggesting the maturation of salivary glands and
      saliva contents for blood feeding. Proteins involved in blood feeding, i.e.,
      putative 5' nucleotidase/apyrase, anti-platelet protein, long form D7 salivary
      protein, D7-related 1 protein, and gSG6 salivary protein, start to accumulate
      from emergence and gradually increase becoming predominant within 48 h. There are
      different salivary components expressed within each region of the female glands.
      The blood-feeding proteins were detected in the distal-lateral lobes and/or
      medial lobes. Proteins detected and/or identified by this approach could be
      tested in strategies developed to control pathogen and disease transmission.
      Moreover, the information of a 2D map of the female salivary gland could be used
      for comparison with other related species in the A. barbirostris complex to
      distinguish species members in the complex.

PMID- 22584381
TI  - Green tea halts progression of cardiac transthyretin amyloidosis: an
      observational report.
AB  - BACKGROUND: Treatment options in patients with amyloidotic transthyretin (ATTR)
      cardiomyopathy are limited. Epigallocatechin-3-gallate (EGCG), the most abundant
      catechin in green tea (GT), inhibits fibril formation from several amyloidogenic
      proteins in vitro. Thus, it might also halt progression of TTR amyloidosis. This
      is a single-center observational report on the effects of GT consumption in
      patients with ATTR cardiomopathy. METHODS: 19 patients with ATTR cardiomyopathy
      were evaluated by standard blood tests, echocardiography, and cardiac MRI (n = 9)
      before and after consumption of GT and/or green tea extracts (GTE) for 12 months.
      RESULTS: Five patients were not followed up for reasons of death (n = 2),
      discontinuation of GT/GTE consumption (n = 2), and heart transplantation (n = 1).
      After 12 months no increase of left ventricular (LV) wall thickness and LV
      myocardial mass was observed by echocardiography. In the subgroup of patients
      evaluated by cardiac MRI a mean decrease of LV myocardial mass (-12.5 %) was
      detected in all patients. This was accompanied by an increase of mean mitral
      annular systolic velocity of 9 % in all 14 patients. Total cholesterol (191.9 +/-
      8.9 vs. 172.7 +/- 9.4 mg/dL; p < 0.01) and LDL cholesterol (105.8 +/- 7.6 vs.
      89.5 +/- 8.0 mg/dL; p < 0.01) decreased significantly during the observational
      period. No serious adverse effects were reported by any of the participants.
      CONCLUSIONS: Our observation suggests an inhibitory effect of GT and/or GTE on
      the progression of cardiac amyloidosis. We propose a randomized placebo
      controlled investigation to confirm our observation.

PMID- 22584382
TI  - Automated photoplethysmography-based determination of ankle-brachial index: a
      validation study against Doppler sonography.
AB  - INTRODUCTION: Determination of ankle-brachial-index (ABI) by manual Doppler is
      well established to screen for lower extremity arterial disease (LEAD) and to
      predict cardiovascular risk. A new generation of digital-controlled devices
      promises automated ABI determination. The aim of this study was to determine
      comparability of automated photoplethysmography (PPG)-derived ABI calculation
      with the Doppler-ABI algorithm commonly used in cohort studies. METHODS:
      Automated PPG-based ABI measurements [Vascular Explorer (VE) and Vicorder (VI)]
      were recorded from 112 limbs of healthy subjects and 22 limbs of patients with
      confirmed LEAD. Validity was evaluated on the basis of receiver-operating
      characteristic (ROC) analysis of clinical status and concordance with Doppler
      ABI. Differences between cuff inflation [inf]- and deflation [def]-based method
      were studied in VE. RESULTS: PPG-based ABI values were higher compared to Doppler
      ABI (VI +0.06, VEinf +0.15, VEdef +0.09, p < 0.001, respectively). The difference
      was pronounced in pathological (<0.9), borderline (0.9-0.99) and low normal (1.0
      1.09) ABI, but less in ABI >=1.1. However, ROC analysis revealed excellent
      diagnostic value for LEAD (sensitivity/specificity) and comparable area under the
      curve at method-adapted ABI thresholds for all methods: Doppler (95/90 %, 0.95),
      VI (75/96 %, 0.91), VEinf (85/89 %, 0.93) and VEdef (80/98 %, 0.94). CONCLUSIONS:
      Digital-controlled PPG-based ABI determination is a useful diagnostic application
      for LEAD. However, the systematic higher ABI in PPG-based measurement compared to
      Doppler and remarkable differences between the deflationary and inflationary
      method are critical for the interpretation of borderline and low normal ABI
      values where precise reading is essential to detect mild LEAD and subclinical
      disease and to predict cardiovascular risk.

PMID- 22584383
TI  - Counseling reproductive health issues in women with congenital heart disease.
AB  - OBJECTIVES: This study reports on current information sources of women with
      Congenital Heart Disease (CHD) regarding sexuality, pregnancy and contraception.
      STUDY DESIGN: 536 women with CHD, aged 29 years (18-75 years) underwent clinical
      assessment and completed a questionnaire regarding sources of information they
      had received about sexuality, pregnancy and contraception. RESULTS: The sources
      where affected women sought information regarding sexuality, pregnancy or
      contraception were wide spread and varied between the different age groups. Not
      only the treating physician, but also friends were the main information sources.
      Written information from sources such as newspapers, magazines, books and also
      the internet were used less often. Only few women received information from
      affected patients. The women rated their level of information (on a level up to
      10) regarding sexuality with a median of 3.5, and with a median of only 5
      regarding contraception as well as pregnancy. CONCLUSIONS: Current counseling
      practice for pregnancy and contraception in women with CHD is inadequate. Failure
      to give knowledgeable family planning advice appropriate for the individual risk
      profile in this high-risk patient group can have hazardous consequences and cause
      an unnecessary risk for mother and child. Many doctors fail to confront their
      patients with congenital heart defects early with issues of regarding sexuality,
      pregnancy and contraception and to advise them adequately. A cooperative approach
      involving congenital cardiologists as well as experienced gynecological
      endocrinologists with appropriate knowledge about CHD is indispensable.

PMID- 22584385
TI  - Dying in the dark? Strengthening  the contribution of palliative care  to
      advanced dementia care.

PMID- 22584384
TI  - Cubic phases in membrane lipids.
AB  - On the basis of data obtained by time-resolved X-ray diffraction, we consider in
      the present article the occurrence and formation pathways of inverted
      bicontinuous cubic phases, or bilayer cubic phases, Q (II)(B) , in diluted
      dispersions of lipids representing major biomembrane lipid classes
      [phosphatidylethanolamines (PEs), mixtures of PEs and phosphatidylcholines (PCs)
      with other lipids, glycolipids]. We show that Q (II)(B) formation proceeds much
      more easily upon cooling from the H(II) phase than upon heating or isothermal
      conversion from the L(alpha) phase, thus identifying an indirect but faster route
      for Q (II)(B) phase induction in lipids. The data collected consistently show
      that the ability to convert into cubic phase upon temperature cycling appears to
      be a general property of all lipids exhibiting an L(alpha) <-> H(II) phase
      transition. Admixtures of charged phospholipids, both anionic and cationic,
      strongly facilitate Q (II)(B) formation in PEs. Their effect may be attributed to
      increased electrostatic repulsion between the lipid bilayers that reduces the
      unbinding energy and facilitates the dissipation of the L(alpha) phase required
      for its conversion into bilayer cubic phase.

PMID- 22584386
TI  - The 9th Palliative Care Congress:  one attendee's highlights.
AB  - The 9th annual Palliative Care Congress, organised by the Palliative Care
      Research Society and the Association of Palliative Medicine, took place in
      Gateshead, England, on 14-16 March at the impressive The Sage Gateshead on the
      bank of the river Tyne. Proceedings got under way in dramatic fashion with a
      production of the Nell Dunne play Home Death, which International Journal of
      Palliative Nursing part-sponsored. The play was well received by the early comers
      to the Congress, as evidenced by the comment that it was interesting to
      experience the very familiar event of a patient's death from the unfamiliar
      perspective of the person's relatives. This refreshingly alternative start to the
      Congress continued into the official opening next morning, with a vibrant and
      humorous performance from the Newcastle Sword Dancers that no doubt helped to
      cast off the last traces of sleep for many a delegate.

PMID- 22584387
TI  - Exploring district nurses' reluctance  to refer palliative care patients  for
      physiotherapy.
AB  - AIM: To explore district nurses' beliefs regarding referral of a patient
      receiving palliative care for physiotherapy. METHOD: Three focus groups, guided
      by the Theory of Planned Behaviour, were undertaken with a purposive sample of 16
      district nurses. All were audio-recorded, transcribed, and subject to content
      analysis. RESULTS: Nine beliefs were identified as influencing referral
      decisions, the majority of which were negative, such as the belief that
      physiotherapists lack palliative care skills and could foster false hope.
      Additional barriers to referral included a lack of contact and communication with
      physiotherapists, poor knowledge or experience of physiotherapy, unsuitable
      referral systems, and poor availability of services. CONCLUSION: These findings
      help to explain why so few patients receiving palliative care access
      rehabilitation services. To ensure that patients have appropriate access to
      palliative rehabilitation, there needs to be consideration of how the identified
      barriers can be overcome.

PMID- 22584388
TI  - Staff perceptions of the impact  of the Liverpool Care Pathway in aged
      residential care in New Zealand.
AB  - AIM: To determine staff perceptions of the impact of the Liverpool Care Pathway
      for the dying patient (LCP) in three aged residential care facilities in New
      Zealand. METHODS: A mixed methodology approach was adopted, including the use of
      a survey, focus groups, and individual interviews. FINDINGS: Fifteen of 194 staff
      participated in the focus groups (five nurses and nine health-care assistants).
      The interviewees included three GPs, one registered nurse, and one manager. The
      post-implementation survey response rate of 13% was poorer than the 32% response
      rate to a pre-implementation survey reported elsewhere. Nevertheless, there was
      congruence across the data sources. The participating staff perceived multiple
      benefits to residents, family, whanau, and staff following implementation of the
      LCP. CONCLUSION: As a tool the LCP was effective in supporting, guiding, and
      prompting care delivery. However, challenges remained, particularly regarding
      environmental factors.

PMID- 22584389
TI  - Forgotten grievers: an exploration of the grief experiences of bereaved
      grandparents (part 2).
AB  - The death of a child is a traumatic family life event. Although parental
      bereavement has received substantial attention, little research has focused on
      the grief experiences of bereaved grandparents. The aims of this Irish national
      study were to identify and describe the bereavement experiences of grandparents
      following the death of their grandchild and to explore their needs and supports
      throughout. A previous paper provided background to the study, covered the
      methods used in depth, and presented one of the three key findings: 'cumulative
      pain'. The present paper discusses the remaining two findings: factors that
      facilitate and factors that inhibit the resolution of the cumulative pain.
      Several factors were perceived by the bereaved grandparents as being either
      helpful or unhelpful in easing the pain of their grief. Among these were
      acknowledgment of the deceased grandchild and the grandparents themselves, the
      relationship with the bereaved son or daughter, family dynamics, and support
      mechanisms.

PMID- 22584390
TI  - Developing competencies and training to enable senior nurses to take on full
      responsibility for DNACPR processes.
AB  - There is currently great interest and activity around the development of do not
      attempt cardiopulmonary resuscitation (DNACPR) policies in health and social
      care. This paper describes how South Central Strategic Health Authority (SHA) in
      the UK underwent a process of agreeing a competency framework and devising an
      accompanying training course to enable senior nurses to be decision makers and
      signatories for DNACPR forms. The competencies that were agreed are presented,
      along with an exploration of the benefits of nurses completing DNACPR forms,
      including a costing of apparent financial benefits. With the restructuring of
      SHAs on the horizon it is important to share practice development in order to
      avoid duplication of effort.

PMID- 22584391
TI  - A training needs analysis  of neonatal and paediatric health-care staff in a
      tertiary children's hospital.
AB  - INTRODUCTION: Despite clinical advances in neonatal and paediatric palliative
      care, there is limited educational provision to underpin practice. To develop
      appropriate educational content, the needs of staff working in this area must be
      identified. AIM: To explore the educational needs of staff working with families
      with palliative or end-of-life care requirements. METHODS: A training needs
      analysis (TNA) explored the perceived knowledge, confidence, and support of
      neonatal and paediatric health professionals in a tertiary children's hospital in
      London. RESULTS: An online Likert scale TNA was completed by 111 participants.
      The results indicated that the staff did not feel educationally prepared in their
      working areas, despite having regular contact with families with palliative or
      end-of-life care issues. DISCUSSION: Understanding the educational needs of staff
      can underpin the development of appropriate educational interventions. These
      modules require evaluation to determine their impact on health professionals'
      knowledge and confidence.

PMID- 22584394
TI  - Inhibition of microglial activation protects hippocampal neurogenesis and
      improves cognitive deficits in a transgenic mouse model for Alzheimer's disease.
AB  - BACKGROUND: Activated microglia with macrophage-like functions invade and
      surround beta-amyloid (Abeta) plaques in Alzheimer's disease (AD), possibly
      contributing to the turnover of Abeta, but they can also secrete proinflammatory
      factors that may be involved in the pathogenesis of AD. Microglia are known to
      modulate adult hippocampal neurogenesis. OBJECTIVES/METHODS: To determine the
      role of microglia on neurogenesis in brains with Abeta pathology, we inhibited
      microglial activation with the tetracycline derivative minocycline in doubly
      transgenic mice expressing mutant human amyloid precursor protein (APP) and
      mutant human presenilin-1 (PS1). RESULTS: Minocycline increased the survival of
      new dentate granule cells in APP/PS1 mice indicated by more BrdU+/NeuN+ cells as
      compared to vehicle-treated transgenic littermates, accompanied by improved
      behavioral performance in a hippocampus-dependent learning task. Both brain
      levels of Abeta and Abeta-related morphological deficits in the new neurons
      labeled with GFP-expressing retrovirus were unaffected in minocycline-treated
      mice. CONCLUSIONS: These results suggest a role for microglia in Abeta-related
      functional deficits and in suppressing the survival of new neurons, and show that
      modulation of microglial function with minocycline can protect hippocampal
      neurogenesis in the presence of Abeta pathology.

PMID- 22584395
TI  - Aspirations of immortality.

PMID- 22584396
TI  - Thinking falls-taking action: a falls prevention tool for care homes.
AB  - Falls in older people resident within care home settings are common and serious,
      often resulting in injury and mortality. Yet there is no standardised approach
      within UK care homes to assessing the risk of falls for individuals or
      identifying risk factors relevant for that person. The Guide to Action for Falls
      Prevention Tool - Care Homes (GtACH) was developed with local care homes in
      Nottinghamshire. Ten care homes were selected to participate in the study, four
      withdrawing before data collection commenced. Fourteen care home staff across six
      care homes tested the tool for usability and found it quick (20 minutes) and easy
      to use, yet only 53% of the recommended interventions highlighted were completed.
      The GtACH needs further evaluation to test whether its use prompts actions which
      reduce the number of falls, and the barriers to these actions being taken.

PMID- 22584397
TI  - From bowel habits to sexuality:  the taboos of caring in palliative care.

PMID- 22584398
TI  - Chemotherapy in the community for adult patients with cancer.
AB  - The NHS Operating Framework for the NHS in England 2010/11 proposed more
      community-based services for people receiving chemotherapy. This is also
      advocated in the Department of Health publications NHS 2010-15 from good to
      great: preventative, people centred, productive (2009b) and Chemotherapy services
      in the Community - A Guide for PCTs Chemotherapy closer to home (DH, 2010a). This
      article reflects on the provision of chemotherapy services closer to home, with
      the aim of engaging community practitioners in considering this area of service
      provision. It examines the need for this service, reviews the chemotherapy
      pathway, and considers what models have been adopted to deliver this in the
      community. Education and training to ensure patient safety and practitioner
      competence will be briefly considered in light of new national initiatives. The
      article also aims to provide information for service commissioners ahead of the
      transition from PCT to GP commissioning in 2013. Although for several years the
      trend has been towards delivering services closer to home, there is not a wealth
      of research-based literature on this subject. While patient experience can be
      captured and analysed it also needs to be placed in context with that of those
      delivering the service, as safety and quality is paramount. Until then we should
      be optimistically cautious in rolling out these services until the meaning of
      closer to home is defined by local context.

PMID- 22584399
TI  - Nursing's finest hour: part 1. Queen's Nurses in South Africa.

PMID- 22584400
TI  - The Welfare Reform Act:  poverty and the impact on people.

PMID- 22584401
TI  - Reflect for success: use of mentor  recommendations to help failing students.
AB  - Mentoring student nurses (STN) who fail to achieve can be distressing for all
      those involved in the process. A group of community nurse mentors (CNMs) and
      practice learning team teachers (PLTs) made recommendations to manage failing
      students. This paper reflects on the use of the recommendations in practice and
      discusses the impact on practice for the PLT and CNMs.

PMID- 22584402
TI  - ACP conversations in clinical practice: impact of an education initiative.
AB  - This article reports on participants' experiences of facilitating advanced care
      planning (ACP) conversations in their clinical practice following an ACP study
      day. NHS Education for Scotland commissioned an educational package to be
      delivered by designated facilitators across all health boards in Scotland as part
      of the implementation of 'Living and Dying Well in Scotland' (2008). The reported
      impact of this programme on the practice of six nurses is the focus of this
      paper. Six nurses from both community (n=3) and acute care settings (n=3 ) were
      interviewed on a one-to-one basis 10-12 months after attendance at an ACP study
      day. Data were transcribed verbatim and analysed using a comparative approach to
      thematic analysis.  The training was found to have increased participants'
      awareness of ACP, validated their knowledge and skills, and in turn had a
      positive impact on their clinical practice. However, some barriers to providing
      this approach were identified, including time, planning and resource constraints.
      Educational programmes can be beneficial and impact on clinical care. However,
      education is only one way to encourage ACP in health care. The complex and
      transactional nature of ACP should be recognised, alongside the need to pace
      conversations about ACP.

PMID- 22584403
TI  - Extension of controlled drug prescribing rights to independent prescribers.
AB  - After a wait of three years, the Home Office has finally made good on its promise
      to end the confusion over the range and use of controlled drugs by independent
      non-medical prescribers (NMPs). Since 23 April 2012, both nurse and pharmacist
      independent prescribers are able to prescribe a far broader range of controlled
      drugs as part of their practice. In a follow up to their article from November
      (Griffith and Tengnah, 2011) setting out the limits on prescribing controlled
      drugs by NMPs, Richard Griffith and Cassam Tengnah discuss the changes introduced
      by the Misuse of Drugs (Amendment No. 2) (England, Wales and Scotland)
      Regulations 2012 and consider the implications of the changes on practice.

PMID- 22584406
TI  - Immune responses and protection efficacy of a recombinant swinepox virus
      expressing HA1 against swine H3N2 influenza virus in mice and pigs.
AB  - Swine influenza virus (SIV) is not only an important respiratory pathogen in pigs
      but also a potent threat to human health. Even though immunization with
      recombinant vaccinia poxviruses expressing protective antigens as a vaccination
      strategy has been widely used for many infectious diseases, development of
      recombinant swinepox virus (rSPV) vector for this purpose has been less
      successful. Here, we report the construction of a recombinant swinepox virus
      (rSPV) expressing hemagglutinin (HA1) of H3N2 SIV (rSPV-H3). Immune responses and
      protection efficacy of the vaccination vector were assessed in both mouse and pig
      models. Prime and boost inoculations of rSPV-H3 yielded neutralization antibody
      against SIV and elicited potent H3N2 SIV-specific INF-gamma response from T
      lymphocytes. Complete protection of pigs against H3N2 SIV challenge was achieved.
      No pigs showed severe systemic and local reactions and no SIV was found shed from
      the pigs vaccinated with rSPV-H3 after challenge. The data suggest that the SPV
      based recombinant vector expressing HA1 of H3N2 SIV might serve as a promising
      SIV vaccine for protection against SIV infection.

PMID- 22584407
TI  - Excision of a rectal neoplasm using robotic transanal surgery (RTS): a
      description of the technique.
AB  - The approach to local excision of benign and early-stage, well-selected neoplasms
      of the rectum continues to evolve. We demonstrate here that local excision of a
      rectal neoplasm using the da Vinci Robotic Surgical System can be successfully
      performed. To our knowledge, this is the first time robotic transanal surgery
      (RTS) has been used in this manner.

PMID- 22584408
TI  - Is omitting pouchography before ileostomy takedown safe after negative clinical
      examination in asymptomatic patients with pelvic ileal pouch? An observational
      study.
AB  - BACKGROUND: When restorative proctocolectomy (RPC) is performed, a temporary
      diverting loop ileostomy is often fashioned and usually closed 2-3 months later.
      Pouchography is used to assess pouch integrity, although its benefits have been
      questioned and no definitive data support its routine use. Our aim was to assess
      the utility of pouchography before ileostomy closure in patients with a negative
      clinical examination. METHODS: We retrospectively reviewed our database of
      patients who underwent ileostomy takedown between 1987 and 2010. Two hundred and
      thirty-two patients were identified who underwent RPC with a W- or J-pouch for
      ulcerative colitis or familial adenomatous polyposis. Twenty-one patients
      underwent RPC without diversion. Twenty-four symptomatic patients were excluded
      from the study. Only asymptomatic patients with a normal clinical examination
      were enrolled. One patient was lost at follow-up. Hence, 186 patients were
      considered suitable for evaluation. Patients undergoing ileostomy closure without
      any radiological examination were assigned to Group A (n = 132); those operated
      on after a preoperative pouchography to Group B (n = 54). RESULTS: Pouchography
      was normal in 49 (90.7%) Group B patients. None of the 5 (9.3%) Group B patients
      with an abnormal radiographic examination experienced complications. Negative
      pouchography did not exclude future problems. Patients of both groups experienced
      similar early functional impairments. Failure occurred in 3 (2.3%) Group A
      patients and in 2 (3.7%) patients of the pouchography group. CONCLUSIONS:
      Pouchography may be safely omitted before ileostomy takedown if there is no
      clinical or endoscopic evidence of pelvic sepsis or ileo-anal anastomotic
      complications, even in very young patients, provided clinical and endoscopic
      follow-up is carefully performed. All anomalies detected were already suspected
      clinically.

PMID- 22584409
TI  - Glycosylation disorders of membrane trafficking.
AB  - During evolution from prokaryotic to eukaryotic cells, compartmentalization of
      cellular functions has been achieved with a high degree of complexity. Notably,
      all secreted and transmembrane proteins travel through endoplasmic reticulum (ER)
      and Golgi apparatus, where they are synthesized, folded and subjected to covalent
      modifications, most particularly glycosylation. N-glycosylation begins in the ER
      with synthesis and transfer of glycan onto nascent protein and proceeds in Golgi
      apparatus where maturation occurs. This process not only requires the precise
      localization of glycosyltransferases, glycosidases and substrates but also an
      efficient, finely regulated and bidirectional vesicular trafficking among
      membrane-enclosed organelles. Basically, it is no surprise that alterations in
      membrane transport or related pathways can lead to glycosylation abnormalities.
      During the last few years, this has particularly been highlighted in genetic
      diseases called CDG (Congenital Disorders of Glycosylation). Alterations in
      mechanisms of vesicle formation due to COPII coat component SEC23B deficiency, or
      in vesicles tethering, caused by defects of the COG complex, but also impaired
      Golgi pH homeostasis due to ATP6V0A2 defects have been discovered in CDG
      patients. This mini review will summarize these fascinating discoveries.

PMID- 22584411
TI  - A comparative expression analysis of gene transcripts in brain tissue of non
      transgenic and GH-transgenic zebrafish (Danio rerio) using a DDRT-PCR approach.
AB  - The presence of higher level of exogenous growth hormone (GH) in transgenic
      animals could lead to several physiological alterations. A GH transgenic
      zebrafish (Danio rerio) line was compared to nontransgenic (NT) samples of the
      species through a DDRT-PCR approach, with the goal of identifying candidate
      differentially expressed transcripts in brain tissues that could be involved in
      GH overexpression. Densitometric analyses of two selected amplification products,
      p300 and ADCY2, pointed to a significant lower gene expression in the transgenic
      zebrafish (104.02 +/- 57.71; 224.10 +/- 91.73) when compared to NT samples
      (249.75 +/- 30.08; 342.95 +/- 65.19). The present data indicate that p300 and
      ADCY2 are involved in a regulation system for GH when high circulating levels of
      this hormone are found in zebrafishes.

PMID- 22584412
TI  - Effects of anidulafungin and voriconazole, singly and in combination, on
      cytokine/chemokine production by human monocyte-derived macrophages infected with
      Candida glabrata or activated by lipopolysaccharide.
AB  - BACKGROUND: Candida glabrata causes infections associated with severe sepsis,
      production of high concentrations of cytokines/chemokines, and high mortality.
      This study describes the effects of anidulafungin (ANF) and voriconazole (VRC),
      singly and in combination, on the production of eight cytokines/chemokines by
      human monocyte-derived macrophages (MDM) infected with C. glabrata or activated
      by lipopolysaccharide (LPS). METHODS: MDM monolayers were established, infected
      with C. glabrata or activated with LPS, and then treated with high or low
      concentrations of ANF, VRC, or both. Cytokine/chemokine levels in MDM
      supernatants were determined. RESULTS: Levels of cytokines/chemokines were
      significantly elevated in supernatants of infected or LPS-activated MDM. Except
      for interleukin-10, all significant decreases in cytokine/chemokine
      concentrations (p < 0.01) occurred in supernatants of infected MDM treated with
      high concentrations of ANF or ANF + VRC. CONCLUSIONS: Decreases in
      cytokine/chemokine levels in supernatants of infected MDM treated with high
      concentrations of ANF or ANF + VRC suggest that similar treatment could improve
      survival in patients with severe, invasive C. glabrata infections and markedly
      elevated levels of serum cytokines/chemokines.

PMID- 22584413
TI  - Antiplatelet effect of new lipophilic hydroxytyrosol alkyl ether derivatives in
      human blood.
AB  - PURPOSE: To investigate the in vitro antiplatelet and anti-inflammatory effects
      of five alkyl hydroxytyrosol (HT) ether derivatives in human whole blood and
      compare these effects with those of HT. METHODS: Blood samples from healthy
      volunteers were incubated with HT and HT alkyl ether derivatives (ethyl, butyl,
      hexyl, octyl and dodecyl). Maximum intensity of platelet aggregation was induced
      with collagen, arachidonic acid or ADP. Calcium-induced thromboxane B(2) and
      nitric oxide production, LPS-induced prostaglandin E(2) and nitric oxide
      production and LPS-induced interleukin 1beta production were measured. RESULTS:
      All compounds inhibited platelet aggregation, thromboxane B(2) and inflammatory
      mediators in a concentration-dependent manner. The concentrations of each
      compound that inhibited the corresponding variable by 50 % compared to control
      samples (IC(50)) were in the range of 10(-7)-10(-6) M for HT hexyl ether; for the
      other compounds, these values were in the range of 10(-5) M. The IC(50) for
      thromboxane B(2) production was in the range of 10(-4) M. The effects of HT alkyl
      ether derivatives were greater than those of HT. These compounds increased nitric
      oxide production. There was no direct relationship between the effects of these
      compounds and alkyl chain length. Maximum effects were observed in the C4-C6
      range. CONCLUSIONS: Alkyl ether derivatives of HT exert antiplatelet and anti
      inflammatory effects that are greater than those of HT.

PMID- 22584414
TI  - Increased linoleic acid/alpha-linolenic acid ratio in Swedish cord blood samples
      collected between 1985 and 2005.
AB  - BACKGROUND: Cord serum (CS) phospholipid fatty acid composition is associated
      with maternal diet during foetal life, and maternal intake of linoleic acid (LA,
      C18:2omega-6) and alpha-linolenic acid (LNA, C18:3 omega-3) has been shown to
      influence the LA and LNA levels in CS. A possible connection between the
      increased incidence of atopic diseases and increased intake of LA and decreased
      intake of LNA in the Western world has been proposed. AIM: The aim of this study
      was to explore phospholipid fatty acid proportions and total IgE levels in CS
      from Swedish children, collected from 1985 to 2005, a period with increasing
      frequency of allergic diseases in Sweden, and reveal possible changes over time.
      METHOD: Phospholipid fatty acids and total IgE antibodies were analysed with gas
      chromatography and UniCAP((r)) technology, respectively, in 300 CS samples.
      RESULTS: The proportions of LA and LNA decreased significantly from 1985 to 2005
      (p < 0.001 for both). However, the LA/LNA ratio did increase (p < 0.001),
      revealing a relatively larger decrease in LNA than in LA. No correlations were
      found between omega-6 and omega-3 fatty acids and total IgE antibodies in CS from
      newborn children. CONCLUSIONS: The LA/LNA ratio increased (p < 0.001) in cord
      serum samples collected between 1985 and 2005, and no correlations between fatty
      acids and total IgE were found.

PMID- 22584416
TI  - Anthocyanins in the diet of children and adolescents: intake, sources and trends.
AB  - PURPOSE: Anthocyanin intake estimations in large cohorts include almost
      exclusively adults. For the purpose of early dietary prevention, however, it is
      of great interest to estimate anthocyanin intake of children and adolescents.
      METHODS: Anthocyanidin content values from the USDA Database (excluding the
      values for bananas and nuts) were assigned to foods consumed by 4-18-year-old
      participants of the DONALD Study. Between 1990 and 2009, 920 participants
      provided 6,707 3-day weighed dietary records. Intake of anthocyanins (expressed
      as their aglycones anthocyanidins) and their food sources were determined. For
      investigating age and time trends in anthocyanidin density (mg/MJ), a polynomial
      mixed regression model was built. RESULTS: We found the estimated median
      anthocyanidin intake to be around 6 mg/day, strawberries representing the main
      source. Anthocyanidin density of the diet was about 0.2 mg/MJ higher in girls
      than in boys, decreased with age, decreased over time in the first half of the
      study period and increased over time thereafter. CONCLUSIONS: Anthocyanin intake
      in the young is characterised by differences in anthocyanidin density of the diet
      between girls and boys and by decreasing density from young childhood to
      adolescence. Observations in this German study population should be extended by
      further studies in other countries.

PMID- 22584418
TI  - Zinc-coated carbonate apatite derived from avian eggshell for potential use as
      bone substitute. Part I:  preparation and properties.
AB  - PURPOSE: To develop antibacterial bone substitutes derived from avian eggshell
      using microwave processing to convert natural calcium carbonate (CaCO3) into zinc
      coated carbonate apatite (CHA). METHODS: Zinc-coated carbonate apatite was
      prepared using domestic microwave and then characterized with scanning electron
      microscopy (SEM), x-ray diffraction (XRD), Fourier transform infrared
      spectroscopy (FT-IR), and energy dispersive x-ray analysis (EDXA). The trial
      animal study was conducted by filling different bone substitutes into 5-mm
      diameter standard defects on the parietal bone of New Zealand rabbits to observe
      new bone formation for 8 weeks. RESULTS: SEM, XRD, FT-IR, and EDXA confirmed
      characteristics of zinc-coated CHA derived from avian eggshell using microwave
      method. Histological analysis demonstrated that the defects filled with carbonate
      apatite had more calcified bone and less uncalcified bone formation than other
      groups. CONCLUSIONS: The present research demonstrated the efficient use of
      microwave in the conversion of natural CaCO3 into CHA with zinc coating. The
      examined properties showed the potential use of the new material as an
      antibacterial bone substitute in oral surgery. The trial animal study implied
      favorable osteoconductive ability of carbonate apatite in new bone formation.

PMID- 22584419
TI  - Nonprocessed adipose tissue graft in the treatment of dehiscence bone defects in
      rabbit tibiae:  a pilot study.
AB  - OBJECTIVE: To evaluate the bone repair of surgically created dehiscence-type
      defects (3 * 5 mm) around dental implants in rabbit tibia using nonprocessed
      adipose tissue graft or autogenous bone graft. MATERIALS AND METHODS: The bone
      defects were randomly assigned to 3 groups: blood clot (C), autogenous bone (AB),
      and nonprocessed adipose tissue (AT). After 3 months, the animals were
      euthanized. Histomorphometric analyses were performed, and the results were
      analyzed with analysis of variance and Tukey tests (P <= 0.05). Statistics were
      performed for the percentage of the bone-to-implant contact (BIC) and bone area
      (BA) within the limits of the threads. RESULTS: The results for BIC in the AT
      (37.75% +/- 28.03%) and C (40.57 +/- 13.71%) groups were statistically similar,
      whereas the AB group had the greatest percentage of BIC (83.37% +/- 11.85%). For
      all groups, the BA percentage was similar (61.48% +/- 30.89% in AT; 72.90% +/-
      14.10% in C; 84.23% +/- 11.96% in AB), with no statistically significant
      differences. CONCLUSION: Nonprocessed adipose tissue is not a comparable
      substitute for autogenous bone in the treatment of dehiscence bone defects around
      titanium dental implants.

PMID- 22584415
TI  - The role of adipokines in connective tissue diseases.
AB  - OBJECTIVE: To discuss the relationship between adipokines and connective tissue
      diseases, by putting special emphasis on the potential role of leptin,
      adiponectin, resistin, and other adipose tissue products in the pathogenesis of
      rheumatoid arthritis and systemic lupus erythematosus and on possible application
      of adipokine-targeted therapy in the treatment of these disorders with emphasis
      on the recent findings. METHODS: PubMed literature search complemented by review
      of bibliographies listed in identified articles. RESULTS: Most of the data
      presented by different research groups showed changed levels of leptin,
      adiponectin, and resistin and occasionally also other adipokines in rheumatoid
      arthritis and systemic lupus erythematosus. The relationship between the
      remaining connective tissue diseases and adipokines is less documented.
      CONCLUSIONS: Plasma levels of adipokines might tell us too little about their
      role in connective tissue disorders, whereas adipokine effects on synovial
      tissues might differ from their known metabolic or cardiovascular effects, which
      implies that some re-appraisal of adipokines role may need to take place. It
      still remains obscure whether the observed disturbances in various adipokine
      systems in subjects with connective tissue diseases contribute to their
      development or only reflect the presence or activity of inflammatory process,
      which itself is induced by other pro-inflammatory factors.

PMID- 22584420
TI  - Microstructural and topographical characterization of different surface
      treatments of a surgical titanium alloy for dental implants.
AB  - OBJECTIVE: To perform a topographical characterization of a titanium alloy
      subjected to different surface treatments using roughness evaluation, scanning
      electron microscopy, and atomic force microscopy. MATERIALS AND METHODS: For each
      group, 6 discs of a titanium alloy had their surfaces modified by 4 treatments.
      All surfaces were blasted with Al2O3, cleaned, and the specimens were divided
      into 4 groups: G1, immersion in a standardized acid solution (SAS) (control
      group); G2, immersion in acetone, followed by immersion in SAS; G3, immersion in
      acetone, followed by immersion in SAS, followed by immersion in nitric acid; G4,
      immersion in acetone, followed by immersion in SAS, followed by immersion in
      sulfuric acid. Roughness parameters were determined with a roughness tester, and
      data were statistically analyzed using analysis of variance and Tukey tests
      (alpha = 5%). RESULTS: Regarding the roughness parameters, no significant
      differences were found. Scanning electron microscopy and atomic force microscopy
      showed irregular surfaces with the presence of particles uniformly deposited on
      the surfaces. CONCLUSION: A similar roughness pattern was created for all the
      groups. The images and topographic profiles indicated that all the groups showed
      high levels of roughness.

PMID- 22584421
TI  - Vertical ridge augmentation of the atrophic posterior mandible with a 2-stage
      inlay technique:  a case report.
AB  - The use of a 2-stage inlay technique in atrophic posterior mandibles with more
      than 10-mm thickness and less than 5-mm height above the inferior alveolar nerve
      is described. The first surgical procedure was a basic corticotomy of the buccal
      and lingual bone. One month later, a complete inlay procedure was performed.
      Computed tomography and conventional radiography showed a mean vertical bone gain
      of 11.5 mm. This 2-stage inlay technique avoids the use of chisels to complete
      bone osteotomy and reduces postsurgical nerve disturbances in atrophic posterior
      mandibles. This technique reduces intraprocedure and postoperative patient
      discomfort.

PMID- 22584422
TI  - A current dental ethics dilemma.

PMID- 22584423
TI  - Spirometric reference values for an East-African population.
AB  - BACKGROUND: Accurate interpretation of lung function testing requires appropriate
      reference values. Unfortunately, few African countries have produced spirometric
      reference values for their populations. OBJECTIVES: The present study was carried
      out in order to establish normal lung function values for subjects living in
      Rwanda, East Africa. METHODS: The study was conducted in Kigali, capital of
      Rwanda, and in the rural district of Huye in southern Rwanda. The variables
      studied were forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC)
      and peak expiratory flow. Multiple regression analysis was performed using age,
      height, weight and BMI as independent variables to obtain predicted equations for
      both sexes. RESULTS: Predicted equations for normal lung functions were obtained
      from 740 healthy nonsmoking subjects; 394 were females and 346 were males. Minor
      differences in FEV1 and FVC were observed in comparison with other studies of
      Africans, African-Americans (difference in FEV1 and FVC of less than 5%), Chinese
      and Indians. When compared with selected studies from Caucasians and white
      Americans, our results for FEV1 and FVC were 9-12% and 16-18% lower in men and 12
      23% and 17-28% lower in women, respectively. CONCLUSIONS: This study provides
      reference values for pulmonary function in a healthy, nonsmoking Rwandan
      population and enables comparisons to be made with other prediction equations
      from other populations. Spirometric reference values in our study were similar to
      those obtained in a study of black Americans by Hankinson et al.

PMID- 22584424
TI  - Functional outcomes according to the size of the gastric remnant and type of
      reconstruction following open and laparoscopic proximal gastrectomy for gastric
      cancer.
AB  - BACKGROUND/AIMS: We compared functional outcomes between different types of
      reconstruction following open or laparoscopic 1/2- or 2/3-proximal gastrectomy
      for gastric cancer. METHODOLOGY: Resection and reconstruction were performed by
      one of the following 6 methods, depending on the depth of cancer invasion and the
      date of the procedure relative to introduction of laparoscopic proximal
      gastrectomy: open proximal 2/3-gastrectomy with jejunal interposition (2/3 PG
      int, n=7), open proximal 1/2-gastrectomy with jejunal interposition (1/2 PG-int,
      n=5), laparoscopic proximal 1/2-gastrectomy followed by double tract
      reconstructions with small (3 cm) jejunogastrostomy (L1/2 PG-DT(S), n=19) and
      laparoscopic proximal 1/2-gastrectomy followed by double tract reconstructions
      with large (6 cm) jejunogastrostomy (L1/2PG-DT(L), n=10). Open total gastrectomy
      with jejunal interposition (TG, n=12) and laparoscopic total gastrectomy with
      Roux-en-Y reconstruction (LTG, n=14) represented control procedures. RESULTS:
      Comparison of postoperative/preoperative body weight ratios and food intake
      ratios revealed better preservation among patients with a larger remnant stomach
      and with easy flow of food into the remnant stomach (the 1/2PG-int and L1/2PG
      DT(L) groups). CONCLUSIONS: Better functional outcomes were observed in patients
      with a large remnant stomach and with easy flow of food into the remnant stomach
      regardless of whether they underwent open or laparoscopic procedures.

PMID- 22584425
TI  - Prognoses of GEP-NETS with undetermined malignant potentials of their primary
      sites.
AB  - BACKGROUND/AIMS: In gastroenteropancreatic neuroendocrine tumors (GEP-NETs),
      primary lesions cannot be resected when the patients have highly advanced disease
      or when the primary sites are undefined. Such GEP-NETs cannot be evaluated with
      Ki-67 or the mitotic index. The aim of this study was to examine the prognosis of
      GEP-NETs that were ungraded by WHO G1-3 grading (U-NET group). METHODOLOGY:
      Between 2000 and 2011, 75 patients with sporadic GEP-NETs were treated at our
      institution. The prognosis of patients graded as new WHO grading (G-NET group)
      was compared with that of the U-NET group. Cox proportional hazard regression
      analyses were performed to estimate the risk factors for overall survival (OS).
      RESULTS: Overall 1-, 3- and 5-year survival rates were 90.7%, 79.9% and 74.9%,
      respectively. The odds ratio (OR) of patients with synchronous liver metastasis
      and U-NET was 1.73 (p=0.01) and 5.84 (p=0.002), respectively. Multivariate
      analyses of OS according to baseline characteristics revealed the only
      independent risk factor to be U-NET (OR, 3.95; p=0.02). CONCLUSIONS: The
      malignant potential of U-NET may be no less than that of G-NET, while WHO-G3
      patients have the worst prognoses in the G-NET group.

PMID- 22584426
TI  - Persistence of a Mesozoic, non-therian mammalian lineage (Gondwanatheria) in the
      mid-Paleogene of Patagonia.
AB  - We describe two isolated molariforms recovered from early-middle Eocene (early
      Lutetian) levels of northwestern Patagonia, Argentina. Comparisons with major
      lineages of therian and non-therian mammals lead us to refer them to a new genus
      and species of Gondwanatheria (Allotheria). There is a single root supporting
      each tooth that is very short, wide, rounded, and covered by cementum; the steep
      sidewalls, lack of a neck between the crown and root, and the heavily worn stage
      in both molariforms suggest that they were of a protohypsodont type. Both teeth
      are strongly worn at their centers, all along their length, with the labial edge
      less worn than the lingual; they show strong transverse crests that alternate
      with lingual grooves. The protohypsodont aspect of the teeth, as well as the
      strong, transverse crests, are suggestive of sudamericid affinities; on the other
      hand, the thin enamel layer and the occlusal pattern formed by the crests and
      grooves shows more similarities to molariform teeth of the Ferugliotheriidae. The
      new taxon adds evidence regarding the (1) extensive radiation of the
      Gondwanatheria throughout the Southern Hemisphere, (2) persistence of several
      lineages well after the Cretaceous/Paleogene boundary, and (3) early evolution of
      hypsodont types among South American herbivorous mammals.

PMID- 22584428
TI  - Role of p(Z)-pi(Ar/Nap) conjugation in structures of 1
      (arylchalcogena)naphthalenes for Z = Te versus Se, S and O: experimental and
      theoretical investigations.
AB  - Magnitudes of the p(Z)-pi(Ar/Nap) conjugation were evaluated for 1
      (arylchalcogena)naphthalenes (1-(ArZ)Nap, 1-(p-YC(6)H(4)Z)C(10)H(7); 1 (Z = Te),
      2 (Se), 3 (S) and 4 (O)). Structures of 1 were determined by X-ray analysis for Y
      = NMe(2) (b), OMe (c) and CN (i). For 1b and 1c that have electron donating Y,
      the Z-C(Ar) bond is located on the naphthyl plane with Z-C(Nap) being
      perpendicular to the aryl plane, which we define as (B: pd). On the other hand,
      the structure of 1i with electron donating Y is (A: pl), of which Z-C(Ar) is
      placed almost perpendicular to the naphthyl plane with Z-C(Nap) being located on
      the aryl plane. Each structure of 1a (Y = H), 1b, 1c, 1d (Me), 1e (F), 1f (Cl),
      1g (Br), 1h (COOEt), 1i and 1j (NO(2)) was determined by NMR in chloroform-d.
      Structures of 1 in the solutions are (B: pd) for b, c and e that have electron
      donating Y, (A: pl) for f-j with electron accepting Y, and in equilibrium between
      (B: pd) and (A: pl) for a and d of which Y are rather neutral. The results for 2
      4 are very similar to those of 1 in solutions. Quantum chemical calculations were
      performed on 1-4 with Y of a, b' (NH(2)), d, f and j. Magnitudes of the p(Z)
      pi(Ar/Nap) conjugation were well-evaluated by NBO (natural bond orbital)
      analysis. The values were 12.6 and 13.0 kcal mol(-1) for the typical forms of (A:
      pl) and (B: pd) of 1a, respectively, resulting in a much smaller energy
      difference between the two (0.4 kcal mol(-1)), which should correspond to the
      observed result. It is well-demonstrated that the p(Te)-pi(Ar/Nap) conjugation
      operates effectively in 1, although the magnitudes increase in the order of Z =
      Te < Se < S < O. Thermal effect of the Gibbs free energies is shown to play an
      important role in the energy profiles of 1a-4a.

PMID- 22584427
TI  - Body size phenotypes are heritable and mediate fecundity but not fitness in the
      lepidopteran frugivore Cydia pomonella.
AB  - The inheritance and functional roles of quantitative traits are central concerns
      of evolutionary ecology. We report two sets of experiments that investigated the
      heritability and reproductive consequences of body size phenotypes in a globally
      distributed lepidopteran frugivore, Cydia pomonella (L.). In our first set of
      experiments, we tested the hypotheses that (1) body size is heritable and (2)
      parental body size mediates egg production and offspring survival. Midparent
      offspring regression analyses revealed that body mass is highly heritable for
      females and moderately heritable for males. The contribution of fathers to
      estimates of additive genetic variance was slightly greater than for mothers. Egg
      production increased with mean parental size, but offspring survival rates were
      equivalent. Based on this result, we tested two additional hypotheses in a second
      set of experiments: (3) male size moderates female egg production and egg
      fertility and (4) egg production, egg fertility, and offspring survival rate are
      influenced by female mating opportunities. Females paired with large males
      produced more eggs and a higher proportion of fertile eggs than females paired
      with small males. Females with multiple mating opportunities produced more
      fertile eggs than females paired with a single male. However, egg production and
      offspring survival rates were unaffected by the number of mating opportunities.
      Our experiments demonstrate that body mass is heritable in C. pomonella and that
      size phenotypes may mediate fecundity but not fitness. We conclude that male size
      can influence egg production and fertility, but female mate choice also plays a
      role in determining egg fertility.

PMID- 22584429
TI  - Enhanced activity of Rhizomucor miehei lipase by directed evolution with
      simultaneous evolution of the propeptide.
AB  - Propeptides are short sequences that facilitate the folding of their associated
      proteins. The present study found that the propeptide of Rhizomucor miehei lipase
      (RML) was not proteolytically removed in Escherichia coli. Moreover, RML was not
      expressed if the propeptide was removed artificially during the cloning process
      in E. coli. This behavior in E. coli permitted the application of directed
      evolution to full-length RML, which included both propeptide and catalytic
      domain, to explore the role played by the propeptide in governing enzyme
      activity. The catalytic rate constant, k (cat), of the most active mutant RML
      protein (Q5) was increased from 10.63 +/- 0.80 to 71.44 +/- 3.20 min(-1) after
      four rounds of screening. Sequence analysis of the mutant displayed three
      mutations in the propeptide (L57V, S65A, and V67A) and two mutations in the
      functional region (I111T and S168P). This result showed that improved activity
      was obtained with essential involvement by mutations in the propeptide, meaning
      that the majority of mutants with enhanced activity had simultaneous mutations in
      propeptide and catalytic domains. This observation leads to the hypothesis that
      directed evolution has simultaneous and synergistic effects on both functional
      and propeptide domains that arise from the role played by the propeptide in the
      folding and maturation of the enzyme. We suggest that directed evolution of full
      length proteins including their propeptides is a strategy with general validity
      for extending the range of conformations available to proteins, leading to the
      enhancement of the catalytic rates of the enzymes.

PMID- 22584430
TI  - Influence of the surface speciation on biofilm attachment to chalcopyrite by
      Acidithiobacillus thiooxidans.
AB  - Surfaces of massive chalcopyrite (CuFeS2) electrodes were modified by applying
      variable oxidation potential pulses under growth media in order to induce the
      formation of different secondary phases (e.g., copper-rich polysulfides, S n(2-);
      elemental sulfur, S(0); and covellite, CuS). The evolution of reactivity
      (oxidation capacity) of the resulting chalcopyrite surfaces considers a
      transition from passive or inactive (containing CuS and S n(2-)) to active
      (containing increasing amounts of S(0)) phases. Modified surfaces were incubated
      with cells of sulfur-oxidizing bacteria (Acidithiobacillus thiooxidans) for 24 h
      in a specific culture medium (pH 2). Abiotic control experiments were also
      performed to compare chemical and biological oxidation. After incubation, the
      density of cells attached to chalcopyrite surfaces, the structure of the formed
      biofilm, and their exopolysaccharides and nucleic acids were analyzed by confocal
      laser scanning microscopy (CLSM) and scanning electron microscopy coupled to
      dispersive X-ray analysis (SEM-EDS). Additionally, CuS and S n(2-)/S(0)
      speciation, as well as secondary phase evolution, was carried out on biooxidized
      and abiotic chalcopyrite surfaces using Raman spectroscopy and SEM-EDS. Our
      results indicate that oxidized chalcopyrite surfaces initially containing
      inactive S n(2-) and S n(2-)/CuS phases were less colonized by A. thiooxidans as
      compared with surfaces containing active phases (mainly S(0)). Furthermore, it
      was observed that cells were partially covered by CuS and S(0) phases during
      biooxidation, especially at highly oxidized chalcopyrite surfaces, suggesting the
      innocuous effect of CuS phases during A. thiooxidans performance. These results
      may contribute to understanding the effect of the concomitant formation of
      refractory secondary phases (as CuS and inactive S n(2-)) during the biooxidation
      of chalcopyrite by sulfur-oxidizing microorganisms in bioleaching systems.

PMID- 22584431
TI  - Reactive oxygen species generated in the presence of fine pyrite particles and
      its implication in thermophilic mineral bioleaching.
AB  - In the tank bioleaching process, maximising solid loading and mineral
      availability, the latter through decreasing particle size, are key to maximising
      metal extraction. In this study, the effect of particle size distribution on
      bioleaching performance and microbial growth was studied through applying
      knowledge based on medical geology research to understand the adverse effects of
      suspended fine pyrite particles. Small-scale leaching studies, using pyrite
      concentrate fractions (106-75, 75-25, -25 MUm fines), were used to confirm
      decreasing performance with decreasing particle size (D 50 <40 MUm). Under
      equivalent experimental conditions, the generation of the reactive oxygen species
      (ROS), hydrogen peroxide and hydroxyl radicals from pyrite was illustrated. ROS
      generation measured from the different pyrite fractions was found to increase
      with increasing pyrite surface area loading (1.79-74.01 m(2) L(-1)) and Fe(2+)
      concentration (0.1-2.8 g L(-1)) in solution. The highest concentration of ROS was
      measured from the finest fraction of pyrite (0.85 mM) and from the largest
      concentration of Fe(2+) (0.78 mM). No ROS was detected from solutions containing
      only Fe(3+) under the same conditions tested. The potential of ROS to inhibit
      microbial performance under bioleaching conditions was demonstrated. Pyrite-free
      Sulfolobus metallicus cultures challenged with hydrogen peroxide (0.5-2.5 mM)
      showed significant decrease in both cell growth and Fe(2+) oxidation rates within
      the concentration range 1.5-2.5 mM. In combination, the results from this study
      suggest that conditions of large pyrite surface area loading, coupled with high
      concentrations of dissolved Fe(2+), can lead to the generation of ROS, resulting
      in oxidative stress of the microorganisms.

PMID- 22584432
TI  - L-leucine 5-hydroxylase of Nostoc punctiforme is a novel type of Fe(II)/alpha
      ketoglutarate-dependent dioxygenase that is useful as a biocatalyst.
AB  - L-Leucine 5-hydroxylase (LdoA) previously found in Nostoc punctiforme PCC 73102
      is a novel type of Fe(II)/alpha-ketoglutarate-dependent dioxygenase. LdoA
      catalyzed regio- and stereoselective hydroxylation of L-leucine and L-norleucine
      into (2S,4S)-5-hydroxyleucine and (2S)-5-hydroxynorleucine, respectively.
      Moreover, LdoA catalyzed sulfoxidation of L-methionine and L-ethionine in the
      same manner as previously described L-isoleucine 4-hydroxylase. Therefore LdoA
      should be a promising biocatalyst for effective production of industrially useful
      amino acids.

PMID- 22584433
TI  - Biochemical characterization of a GH53 endo-beta-1,4-galactanase and a GH35 exo
      beta-1,4-galactanase from Penicillium chrysogenum.
AB  - An endo-beta-1,4-galactanase (PcGAL1) and an exo-beta-1,4-galactanase (PcGALX35C)
      were purified from the culture filtrate of Penicillium chrysogenum 31B. Pcgal1
      and Pcgalx35C cDNAs encoding PcGAL1 and PcGALX35C were isolated by in vitro
      cloning. The deduced amino acid sequences of PcGAL1 and PcGALX35C are highly
      similar to a putative endo-beta-1,4-galactanase of Aspergillus terreus (70% amino
      acid identity) and a putative beta-galactosidase of Neosartorya fischeri (72%),
      respectively. Pfam analysis revealed a "Glyco_hydro_53" domain in PcGAL1.
      PcGALX35C is composed of five distinct domains including "Glyco_hydro_35,"
      "BetaGal_dom2," "BetaGal_dom3," and two "BetaGal_dom4_5" domains. Recombinant
      enzymes (rPcGAL1 and rPcGALX35C) expressed in Escherichia coli and Pichia
      pastoris, respectively, were active against lupin galactan. The reaction products
      of lupin galactan revealed that rPcGAL1 cleaved the substrate in an endo manner.
      The enzyme accumulated galactose and galactobiose as the main products. The
      smallest substrate for rPcGAL1 was beta-1,4-galactotriose. On the other hand,
      rPcGALX35C released only galactose from lupin galactan throughout the reaction,
      indicating that it is an exo-beta-1,4-galactanase. rPcGALX35C was active on both
      beta-1,4-galactobiose and triose, but not on lactose, beta-1,3- or beta-1,6
      galactooligosaccharides even after 24 h of incubation. To our knowledge, this is
      the first report of a gene encoding a microbial exo-beta-1,4-galactanase. rPcGAL1
      and rPcGALX35C acted synergistically in the degradation of lupin galactan and
      soybean arabinogalactan. Lupin galactan was almost completely degraded to
      galactose by the combined actions of rPcGAL1 and rPcGALX35C. Surprisingly,
      neither rPcGAL1 nor rPcGALX35C released any galactose from sugar beet pectin.

PMID- 22584434
TI  - High let-7a microRNA levels in KRAS-mutated colorectal carcinomas may rescue anti
      EGFR therapy effects in patients with chemotherapy-refractory metastatic disease.
AB  - Preclinical and experimental data in vivo indicate that Lethal-7 (Let-7) microRNA
      downregulates KRAS with antitumor effects in the presence of activating KRAS
      mutations. We quantified the Let-7a isoform in KRAS-mutated colorectal carcinomas
      from patients who received salvage cetuximab plus irinotecan. The study
      population was retrospectively identified among metastatic colorectal cancer
      patients who underwent third-line therapy with cetuximab plus irinotecan in a
      period when only epidermal growth factor receptor (EGFR) expression was required
      for anti-EGFR therapy. In 59 patients harboring KRAS mutations, Let-7a levels
      were analyzed for association with overall survival (OS) and progression-free
      survival (PFS) times. An exploratory subgroup analysis was performed using the
      rs61764370 (LCS6 T>G) polymorphism that experimentally impairs Let-7 binding to
      KRAS mRNA. In the whole group, higher Let-7a levels were significantly associated
      with better survival outcomes. For the primary OS endpoint, the multivariate
      hazard ratio was 0.82 (95% confidence interval, 0.73-0.91; p = .01). The same
      findings with an accentuated positive effect of high Let-7a levels on both OS and
      PFS times were observed in an exploratory analysis of the 45 wild-type LCS6
      patients (excluding 14 carriers of the LCS6 G allele variant). All survival
      associations were confirmed after excluding patients with KRAS codon 13
      mutations. Among the clinicopathologic features, high Let-7a levels were
      associated with grade 2-3 skin toxicity (p = .002). In patients with KRAS
      mutations, Let-7a analysis may serve to identify subgroups of patients who may
      still benefit from EGFR inhibition and this may open up new perspectives for
      alternative treatment strategies.

PMID- 22584435
TI  - High ERK protein expression levels correlate with shorter survival in triple
      negative breast cancer patients.
AB  - The mitogen-activated protein kinase (MAPK) signaling pathway is known to be
      activated in triple-negative breast cancer (TNBC). Extracellular signal-related
      kinase (ERK), a member of the MAPK pathway, promotes cell proliferation,
      angiogenesis, cell differentiation, and cell survival. To assess the prognostic
      impact of ERK in TNBC patients, relative quantities of ERK (ERK-2 and pMAPK) and
      direct targets of the ERK pathway (MAPK/ERK kinase 1, phospho-enriched protein in
      astrocytes [PEA]-15, phosphorylated (p)PEA-15, tuberous sclerosis protein 2,
      p70S6 kinase, and p27) were measured using reverse-phase protein arrays in tumor
      tissue from patients with TNBC (n = 97) and non-TNBC (n = 223). Protein levels in
      patients with TNBC were correlated with clinical and tumor characteristics and
      outcome. The median age of patients with TNBC was 55 years (range, 27-86 years).
      Disease stage was I in 21%, II in 60%, and III in 20% of the patients. In a
      multivariate analysis, among patients with TNBC, those with ERK-2-overexpressing
      tumors had a lower overall survival rate than those with low ERK-2-expressing
      tumors (hazard ratio [HR], 2.76; 95% confidence interval [CI], 1.19-6.41).
      However, high pMAPK levels were associated with a significantly higher relapse
      free survival rate (HR, 0.66; 95% CI, 0.46-0.95). In conclusion, ERK-2 and pMAPK
      are valuable prognostic markers in TNBC. Further studies are justified to
      elucidate ERK's role in TNBC tumorigenicity and metastasis.

PMID- 22584438
TI  - Association of early versus late initiation of dialysis with mortality:
      systematic review and meta-analysis.
AB  - BACKGROUND/AIMS: The association of the timing of dialysis initiation with
      mortality is controversial. We conducted a meta-analysis to determine the
      relationship between the risk of death and early initiation of dialysis, when the
      patient has a greater estimated glomerular filtration rate (eGFR). METHODS:
      Prospective and retrospective cohort studies that independently measured the
      effect of early vs. late initiation of dialysis on risk of death were identified
      by review of several databases. Odds ratios (ORs) were estimated by comparison of
      the highest and lowest quartiles and combined by a random-effects model. RESULTS:
      15 studies (1,285,747 patients) met the inclusion criteria. Summary estimates
      indicated that early start of dialysis was associated with increased risk of
      mortality (OR = 1.33, 95% confidence interval (CI): 1.18-1.49, p < 0.00001).
      Subgroup analysis indicated that early starters were 6.61 years older (p <
      0.00001) and more likely to have diabetes (OR = 2.23, 95% CI: 1.83-2.71, p <
      0.00001) than late starters. Analysis of pooled results of early and late
      starters indicated that older age (OR = 1.18, 95% CI: 1.05-1.33, p = 0.006),
      diabetes (OR = 1.61, 95% CI: 1.38-1.87, p < 0.00001), and high comorbidity index
      score (OR = 2.38, 95% CI: 1.75-3.25, p < 0.00001) were strongly associated with
      increased risk of death. CONCLUSION: Our meta-analysis indicates that early
      initiation of dialysis (at higher eGFR) was associated with an increased risk of
      death. Older age, greater likelihood of diabetes, and the presence of severe
      comorbid disease(s) partly explain this effect.

PMID- 22584436
TI  - Inflammatory breast cancer: what we know and what we need to learn.
AB  - PURPOSE: We review the current status of multidisciplinary care for patients with
      inflammatory breast cancer (IBC) and discuss what further research is needed to
      advance the care of patients with this disease. DESIGN: We performed a
      comprehensive review of the English-language literature on IBC through
      computerized literature searches. RESULTS: Significant advances in imaging,
      including digital mammography, high-resolution ultrasonography with Doppler
      capabilities, magnetic resonance imaging, and positron emission tomography
      computed tomography, have improved the diagnosis and staging of IBC. There are
      currently no established molecular criteria for distinguishing IBC from
      noninflammatory breast cancer. Such criteria would be helpful for the diagnosis
      and development of novel targeted therapies. Combinations of neoadjuvant systemic
      chemotherapy, surgery, and radiation therapy have led to an improved prognosis;
      however, the overall 5-year survival rate for patients with IBC remains very low
      (~30%). Sentinel lymph node biopsy and skin-sparing mastectomy are not
      recommended for patients with IBC. CONCLUSION: Optimal management of IBC requires
      close coordination among medical, surgical, and radiation oncologists, as well as
      radiologists and pathologists. There is a need to identify molecular changes that
      define the pathogenesis of IBC to enable eradication of IBC with the use of IBC
      specific targeted therapies.

PMID- 22584439
TI  - Can left atrial strain and strain rate imaging be used to assess left atrial
      appendage function?
AB  - BACKGROUND: The aim of this study was to evaluate the efficiency of left atrial
      strain (S) and strain rate (SR) imaging in assessing left atrial appendage (LAA)
      function. METHODS: We studied 78 consecutive patients (35 females and 43 males;
      mean age 38 +/- 15 years) referred for transesophageal echocardiography (TEE).
      LAA late emptying velocity (LAA-EV) was calculated. Real-time color Doppler
      myocardial velocity imaging (MVI) data were recorded from the LAA by TEE and the
      lateral wall of the left atrium (LA) by transthoracic echocardiography.
      Longitudinal S and SR were measured in the mid portion of the lateral LA wall and
      lateral LAA wall during the contractile period. LAA late systolic velocity (LSV)
      and LA-LSV were obtained from Doppler analysis. RESULTS: A significant positive
      correlation was detected between LAA-EV and MVI parameters (for LAA-S, r = 0.88,
      p < 0.001; for LAA-SR, r = 0.84, p < 0.001; for LAA-LSV, r = 0.83, p < 0.001; for
      LA-S, r = 0.84, p < 0.001; for LA-SR, r = 0.79, p < 0.001, and for LA-LSV, r =
      0.70, p < 0.001). In addition, a significant positive correlation was detected
      between LAA-S and LA-S (r = 0.85, p < 0.001). CONCLUSION: We suggest that LA-S
      and LA-SR imaging is a beneficial method to evaluate LAA functions noninvasively.

PMID- 22584442
TI  - Flossing or alternative interdental aids?

PMID- 22584441
TI  - The need for inter-professional collaboration.

PMID- 22584443
TI  - A center for oral health promotion: establishing an inter-professional paradigm
      for dental hygiene, health care management and nursing education.
AB  - PURPOSE: The need for education about oral health conditions has been discussed
      in recent years. Current research has shown correlations between oral and
      systemic disease. Disease entities have been connected to bacteremia and
      inflammatory process es, both of which can result  from oral pathologies.
      Professionals need to be educated about these connections and advised how, by
      maintaining proper oral health, they may avoid systemic consequences.  Students
      in dental hygiene, health care management and nursing programs can play a vital
      role in this education. By  jointly creating and operating an educational Center
      for Oral Health Promotion, they can better understand each other's professions.
      This will facilitate developing the skill set to reach out to the underserved and
      establish protocols to provide health literacy and care at affordable rates. 
      They can also better appreciate the interconnections between health care delivery
      and its management while gaining skills needed to work in an inter-professional
      setting.  A Center for Oral Health Promotion would expand services typically
      offered in dental hygiene educational settings  as well as expand dental hygiene,
      nursing and health care management student experiences.

PMID- 22584444
TI  - Probiotics for periodontal health: a review of the literature.
AB  - PURPOSE: Periodontal disease is common among U.S. adults, and the practice of
      dental hygiene can be improved by new treatments to control periodontal
      inflammation and destruction. Probiotics, which are defined as live microbes that
      confer health benefits to a host when consumed  in sufficient quantities, may
      offer a low-risk, easy-to-use treatment option for periodontal diseases.
      Experimental probiotic treatments in-vivo and explorations in-vitro published
      from 2005 to 2010 characterize the effects of specific probiotic strains on
      factors  in periodontal health. Data considered includes clinical parameters such
      as gingival index, plaque index, periodontal probing depths and bleeding on
      probing, inhibition versus colonization of known periodontal pathogens and
      markers of the host immune response. Results of these studies suggest  that
      probiotics may benefit periodontal health. Some of the most promising results
      occurred when the probiotic treatment was delivered in the form of a lozenge and
      combined with the traditional treatment of scaling and root planing. Existing
      commercial probiotic products for periodontal health  refer to some of these
      data. Dosage may also play a role in probiotic efficacy for the periodontium.
      More research is needed to define the optimal strain or strains, therapeutic
      dosage, delivery mechanism and patient profile for periodontal probiotics.

PMID- 22584445
TI  - Diabetes educators' knowledge, opinions and behaviors regarding periodontal
      disease and diabetes.
AB  - PURPOSE: The purpose of this study was to determine certified diabetes educators'
      (CDE) knowledge, behaviors and opinions about periodontal disease and diabetes.
      METHODS: A 33 item questionnaire was distributed to CDEs who provide counseling
      and education services  to patients with diabetes. Questions were open and closed
      ended and Likert-scale. A total of 298 CDEs participated in the survey.
      Descriptive statistics were utilized. RESULTS: Most (62%) agreed that CDEs need
      to collaborate with dental professionals in disease management  and 84% indicated
      interest in an oral health component being added to their continuing education.
      Only 20% felt confident in providing an oral health screening to their patients,
      while 51% discussed oral health with their patients and 64% said they have
      referred a patient to a dentist within  the past year. Most (79%) have not
      received formal oral health education. CONCLUSION: The findings indicate that
      CDEs are aware of and agree that there is a link between oral health and systemic
      health and that collaboration with the dental profession would be a positive
      outcome  for their patients, as would oral health topics being added to their
      continuing education courses. By introducing inter-professional collaboration
      between dental professionals and CDEs, and adding an oral health component to CE
      courses, CDEs' ability to educate their patients regarding  the oral/systemic
      link could improve.

PMID- 22584446
TI  - Dimensions of oral care management in Texas hospitals.
AB  - PURPOSE: There is a growing body of evidence that suggests improved oral health
      can help patient outcomes in hospitals. Yet there are indicators that oral care
      in hospitals is less than ideal. This study was conducted to quantify and qualify
      the dimensions of oral care in Texas  hospitals with a focus on the dental
      knowledge, attitudes and practices of nurses and barriers to providing such care.
      METHODS: A random sample of 582 registered nurses, licensed and employed in
      Texas, was surveyed about oral care attitudes, practices and knowledge.
      Frequencies  and Spearman correlations were used to describe and analyze the data
      with SPSS. RESULTS: Ninety-eight respondents returned surveys for a 16.8%
      response rate. Of these, 52% reported their nursing education did not
      ("minimally/not at all") prepare them for oral care  management. However, they
      felt oral health was important (95%), felt responsible for oral care (79%) and
      assessed the oral cavity of their patients (78.6%). Although they reported being
      "knowledgeable" or "very knowledgeable" about oral health management (67%), their
      score on the knowledge questions was low (mean=51%, sd=0.132). There was not a
      significant correlation between the knowledge scores and education levels
      (rho=0.136, p>0.05) or knowledge scores and work areas (rho=-0.080, p>0.05). They
      also reported such barriers as low priority  for oral care, lack of time, no
      mandate and the need for more resources. CONCLUSION: This study revealed that
      nurses experienced a disconnect between feeling responsible yet somewhat
      incapable and/or ill-prepared to provide adequate oral care for their patients.
      This suggests  a possible need for revising nurse education, hospital
      requirements and protocols for performing oral care and employing dental
      professionals in hospitals.

PMID- 22584447
TI  - Assessment and maintenance of dental implants: clinical and knowledge-seeking
      practices of dental hygienists.
AB  - PURPOSE: This study surveyed dental hygienists in order to assess their routine
      approach for dental implant maintenance and to determine if a relationship exists
      between the formal education of dental hygienists and their previous attendance
      and interest in future implant related  continuing education courses. METHODS: A
      survey was distributed to dental hygienists attending an annual national
      continuing education course. Participants voluntarily completed and submitted
      their survey before the end of the first day of the 3 day course. RESULTS: The 
      results indicate that there is a statistically significant relationship between
      the level of formal education and implant related continuing education course
      attendance. Dental hygienists whose formal education did not include dental
      implant care were more likely to attend implant related  continuing education
      courses than those whose formal education included this content. The majority of
      the dental hygienists expressed interest in continuing education courses on
      dental implants. Results of chi-square analysis show a statistically significant
      relationship between the  type of education and interest in attending implant
      related continuing education courses. There was no statistically significant
      difference in continuing education interest between dental hygienists whose
      formal education did or did not include dental implants. CONCLUSION: Additional 
      continuing education courses have been completed by most dental hygienists whose
      curricula did not include formal training on dental implant care. Most dental
      hygienists are interested in gaining additional knowledge whether or not their
      dental hygiene curriculum contained content on dental  implants.

PMID- 22584448
TI  - Perception of oral status as a barrier to oral care for people with spinal cord
      injuries.
AB  - PURPOSE: The purpose of this study was to examine the oral health status of
      people with spinal cord injuries (SCIs) and determine if people with a SCI have
      an accurate perception of their oral status, and if this is potentially a barrier
      to oral care. Methods consisted of a survey  and oral examination given to 92
      willing participants of the Methodist Rehabilitation Center who sustained a SCI.
      The examination consisted of periodontal status using Periodontal Screen and
      Recording IndexTM and dental status using Decayed, Missing, Filled Teeth index.
      Oral health score was  also determined through questioning the participant. These
      scores, retrieved by the dental hygienist, were then compared to what the SCI
      individual's perception of their own oral health. Results indicate their
      perception of oral health was much better than dental assessment showed.
      Additionally,  more than 18% of this population was completely unaware of decay
      which was found in over half of those studied, and more than 60% were unaware of
      periodontal disease that was exhibited in over 75% of those studied. This
      comparison evaluated a major awareness about the need for education and  oral
      care among the SCI population.

PMID- 22584449
TI  - Oral health students as reflective practitioners: changing patterns of student
      clinical reflections over a period of 12 months.
AB  - PURPOSE: The purpose of this study was to determine the levels of reflection
      shown by bachelor of oral health students in relation to their clinical and
      professional practice. METHODS: Reflective learning was embedded as a topic in
      the oral health curriculum within  the discipline of dental hygiene practice.
      Reflective journal writing was integrated with clinical practice and linked with
      assessment requirements. Students' reflective writing was analyzed thematically
      to elucidate levels of reflection based on Boud's 4 Rs of Reflection (review,
      react, relate  and respond) over a period of 12 months. Differences in the levels
      of reflection at different time intervals were examined. RESULTS: Students'
      ability to critically reflect improved over the period of 12 months. The
      predominant level of reflection changed from primarily descriptive  and
      superficial at the start of the academic year to primarily critical and
      relational by the end. As expected, the highest level of critical reflection
      (respond) occurred infrequently, although it became more frequent as the academic
      year progressed. CONCLUSION: Bachelor of oral  health students do reflect
      critically. Regular reflective writing contributed to the development of critical
      reflective skills in the context of clinical and professional development.

PMID- 22584450
TI  - Comparing the risk identification and management behaviors between oral health
      providers for patients with diabetes.
AB  - PURPOSE: Evidence supporting the link between periodontal disease and systemic
      disease continues to grow. To date, little is known about how dental
      professionals incorporate this information into managing diabetic patients. This
      study examines the risk identification and practice  behaviors regarding diabetic
      patients among dentists, hygienists and specialists. METHODS: Responses were
      received from 383 currently practicing oral health professionals in Arkansas. The
      electronic survey consisted of 35 open and closed-ended or Likert-type items.
      Principal  components factor analysis using varimax rotation was used to explore
      underlying dimensions of the questionnaire in order to provide a more
      parsimonious view of the outcomes. Logistic models were fitted to determine best
      practice outcome as a function of knowledge and professional and social  norms.
      RESULTS: Neither knowledge about diabetes (p<0.285) nor provider type (p<0.186)
      was a predictor of practice behavior. Professional and social norms (p<0.001)
      identified those practitioners who felt modifying their management strategies for
      their patients with diabetes  was a necessary component of their practice
      behavior. CONCLUSION: In general, risk assessment was lacking, irrespective of
      whether a clinician was a dentist or dental hygienist. Results indicate oral
      health professionals in Arkansas need to improve the treatment and management of 
      patients with diabetes and periodontal disease.

PMID- 22584451
TI  - Characteristics of dental hygienists based on Holland's career choice theory.
AB  - PURPOSE: The purpose of this study was to survey 1,800 current licensed dental
      hygienists in the U.S. and identify broad and basic interest patterns within
      Holland's 6 General Occupational Themes. METHODS: A national stratified random
      sample of 1,800 members of the  American Dental Hygienists' Association was
      surveyed. Paper and online surveys included the Strong Interest Inventory and the
      Skills Confidence Inventory. Descriptive statistics and independent t-tests were
      used to analyze the data. RESULTS: A total of 928 participants (51.9%)  completed
      and returned the paper survey, while 436 participants (24.4%) also completed the
      online surveys. Results support coding the dental hygiene profession as
      Investigative - Social - Realistic using the General Occupational Themes. Dental
      hygienists had the most significant  mean differences in the Healthcare Services,
      Medical Science and Science Basic Interest Scales as compared to the General
      Representative Sample. CONCLUSION: Holland's 6 General Occupational Themes have
      the potential to help guide student choice regarding dental hygiene as a career.

PMID- 22584452
TI  - A comparison of dental ultrasonic technologies on subgingival calculus removal: a
      pilot study.
AB  - PURPOSE: This pilot study compared the clinical endpoints of the magnetostrictive
      and piezoelectric ultrasonic instruments on calculus removal. The null hypothesis
      stated that there is no statistically significant difference in calculus removal
      between the 2 instruments. METHODS: A quasi-experimental pre- and post-test
      design was used. Eighteen participants were included. The magnetostrictive and
      piezoelectric ultrasonic instruments were used in 2 assigned contra-lateral
      quadrants on each participant. A data collector, blind  to treatment assignment,
      assessed the calculus on 6 predetermined tooth sites before and after ultrasonic
      instrumentation. Calculus size was evaluated using ordinal measurements on a 4
      point scale (0, 1, 2, 3). Subjects were required to have size 2 or 3 calculus
      deposit on the 6 predetermined  sites. One clinician instrumented the pre
      assigned quadrants. A maximum time of 20 minutes of instrumentation was allowed
      with each technology. Immediately after instrumentation, the data collector then
      conducted the post-test calculus evaluation. RESULTS: The repeated  analysis of
      variance (ANOVA) was used to analyze the pre- and post-test calculus data
      (p<=0.05). The null hypothesis was accepted indicating that there is no
      statistically significant difference in calculus removal when comparing
      technologies (p<=0.05). Therefore, under similar  conditions, both technologies
      removed the same amount of calculus. CONCLUSION: This research design could be
      used as a foundation for continued research in this field. Future studies include
      implementing this study design with a larger sample size and/or modifying the
      study design  to include multiple clinicians who are data collectors. Also,
      deposit removal with periodontal maintenance patients could be explored.

PMID- 22584453
TI  - Liver transplantation for hepatocellular carcinoma in non-cirrhotic livers
      regardless of the number and size of tumours?

PMID- 22584454
TI  - Low doses of grape seed procyanidins reduce adiposity and improve the plasma
      lipid profile in hamsters.
AB  - OBJECTIVE: Procyanidins are polyphenolic compounds with beneficial effects on
      health in relation to cardiovascular disease and metabolic syndrome. In this
      study, we evaluated the potential beneficial effects of low doses of a grape seed
      procyanidin extract (GSPE) on body weight and fat deposition. DESIGN: Four groups
      of hamsters were fed either a standard diet (STD) or a high-fat diet (HFD) for 30
      days and supplemented with either GSPE at 25 mg per kg of body weight per day
      (STD-GSPE and HFD-GSPE groups) or vehicle (STD and HFD groups) during the last 15
      days of the study. RESULTS: A significant decrease in body weight gain was
      observed in both GSPE-treated animals at the end of the experiment. GSPE
      treatment significantly reduced the adiposity index and the weight of all the
      white adipose tissue depots studied (retroperitoneal (RWAT), mesenteric (MWAT),
      epididymal (EWAT) and inguinal (IWAT)) in both GSPE-treated groups. GSPE
      administration reversed the increase in plasma phospholipids induced by the HFD
      feeding. In the RWAT, GSPE treatment increased the mRNA expression of genes
      related to beta-oxidation and the glycerolipid/free fatty acid (GL/FFA) cycle,
      mainly in HFD-GSPE animals. In the MWAT, the effects of GSPE at the
      transcriptional level were not as evident as in the RWAT. Moreover, GSPE
      treatment induced heparin-releasable lipoprotein lipase activity in the RWAT and
      MWAT depots. The alterations in the lipid metabolic pathways induced by GSPE were
      accompanied by lower FFA levels in the plasma and decreased lipid and
      triglyceride accumulation in the MWAT. CONCLUSION: The use of GSPE at low doses
      protects against fat accumulation and improves the plasma lipid profile in
      hamsters. We suggest that GSPE exerts these effects in part through the
      activation of both beta-oxidation and the GL/FFA cycle, mainly in the RWAT.

PMID- 22584455
TI  - Challenges in reproducibility of genetic association studies: lessons learned
      from the obesity field.
AB  - A robust replication of initial genetic association findings has proved to be
      difficult in human complex diseases and more specifically in the obesity field.
      An obvious cause of non-replication in genetic association studies is the initial
      report of a false positive result, which can be explained by a non-heritable
      phenotype, insufficient sample size, improper correction for multiple testing,
      population stratification, technical biases, insufficient quality control or
      inappropriate statistical analyses. Replication may, however, be challenging even
      when the original study describes a true positive association. The reasons
      include underpowered replication samples, gene * gene, gene * environment
      interactions, genetic and phenotypic heterogeneity and subjective interpretation
      of data. In this review, we address classic pitfalls in genetic association
      studies and provide guidelines for proper discovery and replication genetic
      association studies with a specific focus on obesity.

PMID- 22584456
TI  - Two-year outcomes of an adjunctive telephone coaching and electronic contact
      intervention for adolescent weight-loss maintenance: the Loozit randomized
      controlled trial.
AB  - This paper reports the final 24-month outcomes of a randomized controlled trial
      evaluating the effect of additional therapeutic contact (ATC) as an adjunct to a
      community-based weight-management program for overweight and obese 13-16-year
      olds. ATC involved telephone coaching or short-message-service and/or email
      communication once per fortnight. Adolescents were randomized to receive the
      Loozit group program-a two-phase behavioral lifestyle intervention with (n=73),
      or without (n=78), ATC in Phase 2. Adolescents/parents separately attended seven
      weekly group sessions (Phase 1), followed by quarterly adolescent sessions (Phase
      2). Assessor-blinded, 24-month changes in anthropometry and metabolic health
      included primary outcomes body mass index (BMI) z-score and waist:height ratio
      (WHtR). Secondary outcomes were self-reported psychosocial and lifestyle changes.
      By 24 months, 17 adolescents had formally withdrawn. Relative to the Loozit
      program alone, ATC largely had no impact on outcomes. Secondary pre-post
      assessment of the Loozit group program showed mean (95% CI) reductions in BMI z
      score (-0.13 (-0.20, -0.06)) and WHtR (-0.02 (-0.03, -0.01)) in both arms, with
      several metabolic and psychosocial improvements. Adjunctive ATC did not provide
      further benefits to the Loozit group program. We recommend that further work is
      needed to optimize technological support for adolescents in weight-loss
      maintenance. Australian New Zealand Clinical Trials Registry Number
      ACTRNO12606000175572.

PMID- 22584457
TI  - Association of symptoms of attention-deficit/hyperactivity disorder with
      childhood overweight adjusted for confounding parental variables.
AB  - OBJECTIVE: There have been numerous reports on association between attention
      deficit/hyperactivity disorder (ADHD) and overweight/obesity in children and
      adolescents; however, most studies adjusted only for a limited number of possible
      confounders. METHODS: We analyzed the data of 11,159 six through seventeen-year
      old participants in the German Health Interview and Examination Survey for
      Children and Adolescents. We determined weight status based on measured
      anthropometry and national reference data by International Obesity Task Force
      criteria. The parent-rated hyperactivity/inattention subscale of the Strengths
      and Difficulties Questionnaire (SDQ-HI) was used as a continuous measure of ADHD
      symptoms. We examined whether the putative confounders socioeconomic status,
      migrant status, parental body mass index (BMI) and parental smoking were
      associated with both SDQ-HI and overweight/obesity. Associations between SDQ-HI
      and overweight/obesity vs normal weight were analyzed by binary logistic
      regression analyses. In the first model, we adjusted for age and sex only and in
      the second model also for the parental confounders. RESULTS: SDQ-HI was
      associated with an increased risk for overweight/obesity in both sexes adjusting
      for age and sex. However, after adjusting for all confounders SDQ-HI was
      associated with an increased risk for overweight/obesity only in adolescent
      females. Socioeconomic status, parental BMI and parental smoking each were
      relevant confounders. Migrant status was also significantly associated with both
      SDQ-HI and overweight/obesity, thus qualifying as a confounder but contributed
      only weakly to the association. CONCLUSIONS: The association between ADHD
      symptoms and overweight/obesity is due to confounding by family background
      variables in all but adolescent girls. Possible reasons for the increased risk
      for overweight/obesity in this subgroup are discussed. We also propose possible
      mechanisms for confounding by parental socioeconomic status, BMI and smoking.

PMID- 22584459
TI  - Possible association of CUX1 gene polymorphisms with antidepressant response in
      major depressive disorder.
AB  - Association between response to antidepressant treatment and genetic
      polymorphisms was examined in two independent Japanese samples of patients with
      major depressive disorder (MDD). Genome-wide approach using the Illumina Human
      CNV370-quad Bead Chip was utilized in the analysis of the 92 MDD patients in the
      first sample. In all, 11 non-intergenic single-nucleotide polymorphisms with
      uncorrected allelic P-value <0.0001 were selected for the subsequent association
      analyses in the second sample of 136 MDD patients. Difference in allele
      distribution between responders and nonresponders were found in the second-stage
      sample for rs365836 and rs201522 of the CUX1 gene (P=0.005 and 0.004,
      respectively). The allelic P-values for rs365836 and rs201522 in both samples
      combined were 0.0000023 and 0.0000040, respectively. Our results provide the
      first evidence that polymorphisms of the CUX1 gene may be associated with
      response to antidepressant treatment in Japanese patients with MDD. 

PMID- 22584458
TI  - Novel rare variants in congenital cardiac arrhythmia genes are frequent in drug
      induced torsades de pointes.
AB  - Marked prolongation of the QT interval and polymorphic ventricular tachycardia
      following medication (drug-induced long QT syndrome, diLQTS) is a severe adverse
      drug reaction (ADR) that phenocopies congenital long QT syndrome (cLQTS) and is
      one of the leading causes for drug withdrawal and relabeling. We evaluated the
      frequency of rare non-synonymous variants in genes contributing to the
      maintenance of heart rhythm in cases of diLQTS using targeted capture coupled to
      next-generation sequencing. Eleven of 31 diLQTS subjects (36%) carried a novel
      missense mutation in genes with known congenital arrhythmia associations or with
      a known cLQTS mutation. In the 26 Caucasian subjects, 23% carried a highly
      conserved rare variant predicted to be deleterious to protein function in these
      genes compared with only 2-4% in public databases (P<0.003). We conclude that the
      rare variation in genes responsible for congenital arrhythmia syndromes is
      frequent in diLQTS. Our findings demonstrate that diLQTS is a pharmacogenomic
      syndrome predisposed by rare genetic variants. 

PMID- 22584460
TI  - Profiling of drug-metabolizing enzymes/transporters in CD33+ acute myeloid
      leukemia patients treated with Gemtuzumab-Ozogamicin and Fludarabine, Cytarabine
      and Idarubicin.
AB  - Genetic heterogeneity in drug-metabolizing enzyme/transporter (DMET) genes
      affects specific drug-related cancer phenotypes. To investigate the relationships
      between genetic variation and response to treatment in acute myeloid leukemia
      (AML), we genotyped 1931 variants on DMET genes in 94 CD33-positive AML patients
      enrolled in a phase III multicenter clinical trial combining Gemtuzumab
      Ozogamicin (GO) with Fludarabine-Cytarabine-Idarubicin (FLAI) regimen, with the
      DMET Plus platform. Two ADH1A variants showed statistically significant
      differences (odds ratio (OR)=5.68, P=0.0006; OR=5.35, P=0.0009) in allele
      frequencies between patients in complete/partial remission and patients without
      response, two substitutions on CYP2E1 (OR=0.13, P=0.001; OR=0.09, P=0.003) and
      one on SLCO1B1 (OR=4.68, P=0.002) were found to differently influence liver
      toxicity, and two nucleotide changes on SULTB1 and SLC22A12 genes correlated with
      response to GO (OR=0.24, P=0.0009; OR=2.75, P=0.0029). Genetic variants were thus
      found for the first time to be potentially associated with differential response
      and toxicity in AML patients treated with a combination of GO-FLAI regimen. 

PMID- 22584461
TI  - Malignant PEComa of the lumbar vertebra: a rare bone tumour.
AB  - We describe the case of a 26-year-old patient with a perivascular epithelioid
      cell tumour (PEComa) involving the 5th lumbar vertebra. Radiological findings,
      pathological features and treatment are presented. We conclude that PEComas
      should be considered in the differential diagnosis of vertebral lesions.

PMID- 22584462
TI  - Normal values of Wiberg's lateral center-edge angle and Lequesne's acetabular
      index--a coxometric update.
AB  - BACKGROUND: The historical pathological cut-off values for Wiberg's lateral
      center-edge (LCE) angle and Lequesne's acetabular index (AI) are below 20 degrees
      and above 12 degrees  for the LCE and AI, respectively. The aim of this study
      was to reassess these two angles more than 50 years after their introduction
      using a standardized conventional radiological measurement method, considering
      changing social habits and their associated physiological changes. METHODS: A
      total of 1,226 anteroposterior radiographs of the pelvis (2,452 hips) were
      obtained according to a strict standardized radiographic technique allowing
      reliable measurements of the LCE angle and the AI. RESULTS: Distributions of the
      LCE and AI were pronouncedly Gaussian, with mean values of 33.6 degrees  for the
      LCE and 4.4 degrees  for the AI. The 2.5th and 97.5th empirical percentiles were
      18.1 and 48.0 degrees  for the LCE and -6.9 and 14.9 degrees  for the AI. These
      intervals contained 95 % of the data in our large sample. Small but statistically
      significant differences between the sexes and right and left hips have been
      demonstrated. Correlation between age and coxometric indices was low. CONCLUSION:
      The above findings do not conflict with the historical benchmarks. Statistical
      differences between sexes and between right and left hips were not clinically
      relevant. No conclusion can be drawn about coxometric indices and clinical
      manifestations of hip dysplasia.

PMID- 22584463
TI  - Increased levels of serum parathyroid hormone and fibroblast growth factor-23 are
      the main factors associated with the progression of vascular calcification in
      long-hour hemodialysis patients.
AB  - The aim of the present study was to assess the frequency and factors associated
      with the progression of vascular calcifications (VCs) using a semiquantitative X
      ray score. We included all prevalent hemodialysis patients with initial
      radiological scores ranging from 0 to 3 according to the severity of the VCs.
      Patients were classified as non-progressors or progressors after 3 years. Among
      the 85 patients, 44.7% were classified as progressors. Only exhibiting high
      levels of serum intact parathyroid hormone (PTH, >190 pg/ml) and fibroblast
      growth factor (FGF)-23 levels (>3,000 RU/ml) is associated with the risk of VC
      progression (OR 5.8, 95% CI 1.7-19.8, p = 0.004). Calcitriol analogs (38%),
      cinacalcet (15%), dialysate calcium (mean 1.48 mmol/l), dialysis session time (4
      8 h) and calcium- (10%) and non-calcium-based phosphate binders (38%) were
      prescribed on an individual basis. Hyperphosphatemia (<10%) and, especially,
      hypercalcemia (1%) and hyperparathyroidism (>585 pg/ml = 0%) were infrequently
      observed. In conclusion, the main factor associated with VC progression was the
      association of higher serum PTH and FGF-23 levels. It remains to be seen whether
      patients should be treated to lower their PTH value, even within the target
      range, using calcitriol analogs, calcimimetics, parathyroidectomy, or by
      modifying the Klotho-FGF-23 axis.

PMID- 22584465
TI  - Uric acid in heart failure: a biomarker or therapeutic target?
AB  - There is a need for a cost-effective prognostic biomarker in heart failure (HF).
      Substantial evidence suggests that uric acid (UA) is an independent marker for
      adverse prognosis in acute and chronic HF of varying severity. Whether UA is a
      merely a marker of poor prognosis or is an active participant in disease
      pathogenesis is currently unknown. In the setting of HF, at least two different
      processes can be responsible for increased UA: increased production, which may
      result from oxidative stress, and decreased excretion due to renal insufficiency,
      which can be a consequence of cardio-renal syndrome, renal congestion, or
      comorbidities. While pioneer studies have raised the possibility of preventing HF
      through the use of UA lowering agents, namely xanthine oxidase inhibitors and
      uricosurics, the literature is still conflicting on whether the reduction in UA
      will result in a measurable clinical benefit. In this review, we examine the
      evidence relating UA to HF prognosis, the mechanisms that contribute to increased
      UA levels in HF, and future novel treatments aimed at reducing UA levels.

PMID- 22584467
TI  - Managing menopausal symptoms.
AB  - OVERVIEW: There are three major categories of symptoms peri- and postmenopausal
      women experience: vasomotor symptoms, sleep difficulties, and mood problems. This
      article reviews the literature on causes and treatments. This is part three of a
      four-part series on postmenopausal health.

PMID- 22584466
TI  - Patient satisfaction after pulmonary resection for lung cancer: a multicenter
      comparative analysis.
AB  - BACKGROUND: Patient satisfaction reflects the perception of the customer about
      the level of quality of care received during the episode of hospitalization.
      OBJECTIVE: To compare the levels of satisfaction of patients submitted to lung
      resection in two different thoracic surgical units. METHODS: Prospective analysis
      of 280 consecutive patients submitted to pulmonary resection for neoplastic
      disease in two centers (center A: 139 patients; center B: 141 patients; 2009
      2010). Patients' satisfaction was assessed at discharge through the EORTC
      InPatSat32 module, a 32-item, multi-scale self-administered anonymous
      questionnaire. Each scale (ranging from 0 to 100 in score) was compared between
      the two units. Multivariable regression and bootstrap were used to verify factors
      associated with the patients' general satisfaction (dependent variable). RESULTS:
      Patients from unit B reported a higher general satisfaction (91.5 vs. 88.3, p =
      0.04), mainly due to a significantly higher satisfaction in the doctor-related
      scales (doctors' technical skill: p = 0.001; doctors' interpersonal skill: p =
      0.008; doctors' availability: p = 0.005, and doctors information provision: p =
      0.0006). Multivariable regression analysis and bootstrap confirmed that level of
      care in unit B (p = 0.006, bootstrap frequency 60%) along with lower level of
      education of the patient population (p = 0.02, bootstrap frequency 62%) were
      independent factors associated with a higher general patient satisfaction.
      CONCLUSION: We were able to show a different level of patient satisfaction in
      patients operated on in two different thoracic surgery units. A reduced level of
      patient satisfaction may trigger changes in the management policy of individual
      units in order to meet patients' expectations and improve organizational
      efficiency.

PMID- 22584468
TI  - Just heavy menses or something more? Raising awareness of von Willebrand disease.
AB  - OVERVIEW: Von Willebrand disease is the most common inherited bleeding disorder,
      with an estimated prevalence of up to 1.3% of the U.S. population, or 4 million
      Americans. It's caused by a deficiency of or defects in von Willebrand factor, a
      protein necessary for blood to clot. Many nurses and other health care providers,
      as well as patients, are unaware of the disorder, its symptoms, and its
      associated risks. Although the disorder occurs equally in males and females, it
      can be more troublesome in females. Heavy menses beginning at menarche is one of
      the most common presentations, but because the disorder is inherited and other
      family members may have similarly heavy menses, the assumption may be that this
      is normal. This article describes von Willebrand disease and its three types,
      explains how to recognize and investigate suggestive symptoms, and outlines
      management strategies.

PMID- 22584469
TI  - Synthesis and characterization of para-pyridine linked NHC palladium complexes
      and their studies for the Heck-Mizoroki coupling reaction.
AB  - This paper describes the synthesis of 1-(pyridine-4-ylmethyl) NHC and their
      Pd(II) and Ag(I) complexes, which are fully characterized. Interestingly, we have
      also synthesized a Pd complex 3a-CO(3) using a more direct treatment of K(2)CO(3)
      with PdCl(2). 3a-CO(3) represents the first reported solid structure of a Pd
      eta(2)-carbonato complex stabilized by an NHC framework. 3a-CO(3) can be easily
      converted to a PdCl(2) derivative by treating it with chloroform. We have found
      these palladium complexes mediate the Heck-Mizoroki coupling with a low catalyst
      loading. Furthermore, we also expand such catalytic manifold toward constructing
      fused polyaromatic substrates, a highly useful class of compounds in
      optoelectronic chemistry.

PMID- 22584471
TI  - Serum osteoprotegerin concentration is associated with carotid atherosclerotic
      plaque in patients with rheumatoid arthritis.
AB  - OBJECTIVE: Osteoprotegerin (OPG), a regulator of bone resorption, is involved in
      the pathogenesis of rheumatoid arthritis (RA) and atherosclerosis. OPG is
      elevated in patients with coronary artery disease, and high OPG levels are
      associated with cardiac disease severity and mortality in the general population.
      The purpose of this study was to investigate the relationship of serum OPG
      levels, traditional coronary risk factors, and RA-related factors to carotid
      atherosclerosis in RA patients. METHODS: Ninety-one RA patients were studied (85
      % women, age 60 +/- 10 years). Serum OPG levels were measured by an enzyme-linked
      immunosorbent assay. The prevalence of carotid plaque was assessed by
      ultrasonographic imaging in all patients. The relationship between various
      clinical characteristics, OPG, and carotid plaque was examined. RESULTS: Serum
      OPG levels were significantly higher in patients with carotid plaque than in
      those without plaque (median level 1,397 vs. 887 pg/mL, respectively; P = 0.006).
      There were no significant differences between RA patients with and without
      carotid plaque with respect to sex, duration of RA, blood pressure, body mass
      index, smoking, low-density lipoprotein cholesterol, Disease Activity Score-28,
      van der Heijde-modified Sharp score, and prednisolone dose. After adjusting for
      age, sex, and C-reactive protein, elevated levels of OPG were still associated
      with a higher prevalence of carotid plaque in patients with RA (P = 0.038).
      CONCLUSION: RA patients suffer from accelerated atherosclerosis and also have
      increased levels of OPG. The serum OPG level is independently associated with
      carotid plaque.

PMID- 22584472
TI  - Recent progress in the treatment of lupus nephritis.
AB  - The treatment of lupus nephritis has seen significant advances during the past
      decade mainly due to the publication of well-designed randomized clinical trials
      (RCTs). The choice of treatment is guided by the histopathologic classification
      but is also influenced by demographic, clinical, and laboratory characteristics
      that allow for the identification of patients at risk for more aggressive
      disease. For the induction arm, low-dose cyclophosphamide regimens and
      mycophenolate mofetil have been validated as alternatives to the established
      National Institutes of Health regimen of high-dose cyclophosphamide; for the
      maintenance phase, azathioprine and mycophenolate compete for treatment of first
      choice. Rituximab is efficacious in real-life clinical practice but ineffective
      in clinical trials. The role of recently approved belimumab in lupus nephritis
      eagerly awaits further documentation. Aggressive management of comorbid
      conditions, such as hypertension and dyslipidemia, is of utmost importance. Here,
      we review the latest advances in lupus nephritis therapy with a focus on recent
      RCTs as well as new biologic agents under development. Furthermore, we propose a
      therapeutic algorithm in an effort to facilitate clinical decision-making in this
      gradually changing landscape. Upcoming European and American recommendations
      should provide further clarification.

PMID- 22584475
TI  - Molecular and kinetic characterization of histamine transport into adult rat
      cultured astrocytes.
AB  - Astrocytes have a key role in the clearance and inactivation of histamine in the
      adult central nervous system, but transporters which mediate histamine uptake
      into astrocytes have not been fully characterized. We therefore investigated the
      kinetic and molecular characteristics of histamine uptake into cultured adult rat
      astrocytes. [(3)H]-histamine was taken up by astrocytes in a temperature-, time-
      and concentration-dependent manner and was inhibited up to 60-70% by 1mM ouabain
      or by substitution of NaCl with choline chloride. Specific [(3)H]-histamine
      uptake, determined as the difference between transport at 37 and 4 degrees C,
      displayed saturation kinetics with the apparent Michaelis-Menten constant (K(m))
      of 141 and 101MUM and the apparent maximal uptake rate (V(max)) of 22.5 and
      17.8pmol/min/mg protein, as estimated from the Woolf and the Eadie-Hofstee plots,
      respectively. Since our data suggested the presence of a carrier-operated
      histamine uptake system, we assessed the possible involvement of the organic
      cation transporters (OCT) 1, 2 and 3, which have been previously described to
      play a role in histamine transport in the central nervous system. Low level mRNA
      expression of all OCT isoforms was detected, but in contrast to rat brain cortex
      homogenate, where OCT3 was the most prominently expressed OCT isoform, OCT2 mRNA
      was the predominant OCT species in cultured astrocytes. However, OCT inhibitors
      corticosterone and decynium 22 (D22) had no effect or only modestly reduced
      [(3)H]-histamine uptake. Thus, our data indicate that adult rat astrocytes
      possess an efficient high-capacity, low-affinity carrier-operated histamine
      uptake system, which does not seem to involve OCTs.

PMID- 22584477
TI  - Single-stage combined decompression for patients with tandem ossification in the
      cervical and thoracic spine.
AB  - STUDY DESIGN: Retrospective study of clinical outcomes of single-staged combined
      cervical and thoracic decompression for patients with tandem ossification (TO).
      OBJECTIVE: To describe primary clinical outcomes of this procedure. TO is
      introduced to described a double ossification lesion of the posterior
      longitudinal ligament (OPLL) or the ligament flavum (OLF) at the cervical,
      thoracic and lumbar spine. In clinical practice, cervical OPLL combined with
      thoracic OPLL or/and OLF are the most common types of TO. However, little is
      known about the clinical outcomes of surgical treatment and there is no consensus
      on the optimal treatment to this combined disorder. METHODS: Between January 2005
      and December 2008, 15 patients of this complicated phenomenon were treated by
      single-staged combined cervical and thoracic decompression in conditions where
      patients' general condition allowed and individuals agreed on. Surgical
      intervention, perioperative complications, and clinical outcomes were reviewed in
      these 15 TO patients who were followed up for more than 2 years (range 2-5
      years). Clinical symptoms were evaluated using the JOA scoring system and
      activity of daily life was evaluated by Nurick classification before surgery, at
      6 months postoperatively, and at final follow-up. Patient satisfaction was
      determined at final follow-up. RESULTS: The mean blood loss was 1,553.3 +/- 735.7
      ml (range 700-2,900 ml) and the mean operation time was 280.7 +/- 53.6 min (range
      220-370 min). The important intraoperative and postoperative complications
      recorded in medical documents included CSF leakage, hematoma, C5 palsy and
      neurological deterioration. The JOA score was significantly higher 6 months after
      surgery (8.1 +/- 1.8 points vs. 11.0 +/- 1.6 points, p < 0.0001), and there was
      no significant change between 6 months after surgery and final follow-up (11.0 +/
      1.6 points vs. 11.3 +/- 2.1, p = 0.5894). The mean Nurick classification
      significantly improved from grade 3.6 +/- 0.7 before surgery to grade 2.5 +/- 0.9
      at 6 months after surgery (p < 0.001), and well maintained as grade 2.3 +/- 1.0
      at final follow-up (p = 0.3343). Three patients had satisfaction scores of 3
      points, 5 had scores of 2 or 1 point, and 2 had score of 0 point. Pearson
      correlation analysis showed a significant positive correlation between
      satisfaction score and JOA score (r = 0.6493, p = 0.0093), and a significant
      negative correlation between satisfaction score and Nurick classification (r = 
      0.5941, p = 0.0195). Besides, perioperative complications and progression of
      tandem ossification which needed revision surgery had significant adverse effect
      on patients' satisfaction. CONCLUSIONS: The results showed that single-staged
      combined decompression could provide comparable clinical outcomes, and patients'
      satisfaction was significantly related with postoperative neurological function.
      In addition, satisfaction score could be decreased by perioperative complications
      and progression of tandem ossification. Thus, this aggressive surgical strategy
      should be used more carefully with emphasis on preoperative communication with
      patients.

PMID- 22584478
TI  - [Spinal vascular malformations].
AB  - Spinal vascular malformations are a group of rare diseases with different
      clinical presentations ranging from incidental asymptomatic findings to
      progressive tetraplegia. This article provides an overview about imaging features
      as well as clinical and therapeutic aspects of spinal arteriovenous
      malformations, cavernomas and capillary telangiectasia.

PMID- 22584479
TI  - [Spinal angiography :  Anatomy, technique and indications].
AB  - Spinal angiography is a diagnostic modality requiring detailed knowledge of
      spinal vascular anatomy. The cervical spinal cord is supplied by the vertebral
      arteries while segmental arteries which are preserved from fetal anatomy, supply
      the thoracic and lumbar regions. As spinal angiography carries the risk of
      paraplegia the indications have to be considered very carefully. Nevertheless,
      spinal angiography should be performed if there is reason to suspect a spinal
      vascular malformation from magnetic resonance imaging (MRI).

PMID- 22584480
TI  - [Spinal dural arteriovenous fistulas : Diagnostics and therapy].
AB  - Spinal dural arteriovenous fistulas are rare spinal vascular malformations which
      can cause progressive paraparesis and paraplegia if not treated. As symptoms are
      unspecific diagnosis is often delayed and clinical outcome is dependent on early
      therapy. While magnetic resonance imaging (MRI) is the first choice imaging
      procedure, selective spinal digital subtraction angiography is necessary to
      analyze the angioarchitecture and to plan the treatment. This article provides an
      overview on the epidemiology, etiology, clinical aspects and imaging features as
      well as therapeutic aspects of spinal dural arteriovenous fistulas. Knowledge of
      spinal vascular anatomy is the basis for understanding spinal dural arteriovenous
      fistulas.

PMID- 22584481
TI  - [Spinal cord infarction].
AB  - Infarction of the spinal cord can cause a variety of symptoms and neurological
      deficits because of the complex vascular supply of the myelon. The most common
      leading symptom is distal paresis ranging from paraparesis to tetraplegia caused
      by arterial ischemia or infarction of the myelon. Venous infarction, however,
      cannot always be distinguished from arterial infarction based on the symptoms
      alone.Modern imaging techniques, such as computed tomography angiography (CTA)
      and magnetic resonance angiography (MRA) assist in preoperative planning of
      aortic operations to reliably identify not only the most important vascular
      structure supplying the spinal cord, the artery of Adamkiewicz, but also other
      pathologies such as tumors or infectious disorders. In contrast to CT, MRI can
      reliably depict infarction of the spinal cord.

PMID- 22584482
TI  - [Spinal epidural hematoma].
AB  - Spinal epidural hematoma is an accumulation of blood in the potential space
      between the dura and bone. On unenhanced computed tomography epidural hemorrhage
      appears as a high-density spinal canal mass with variable cord compression.
      Magnetic resonance imaging is the modality of choice for evaluating spinal
      epidural hematoma and can demonstrate the extent of the hematoma and degree of
      cord compression. When treated surgically the outcome depends on the extent of
      preoperative neurological deficits and on the operative timing interval.

PMID- 22584483
TI  - [Soft tissue swelling of the sternoclavicular joint].
AB  - A 73-year-old woman presented with a swelling of the right sternoclavicular joint
      the size of a hens egg which had persisted for 2 years. After a corticosteroid
      injection 8 months previously the swelling was asymptomatic. The magnetic
      resonance imaging (MRI) scan showed synovialitis of the sternoclavicular joint
      with edema of the adjacent bone. The constellation is indicative of Tietze
      syndrome, an inflammation of costochondral junctions of the ribs or
      chondrosternal joints. The treatment is usually directed at pain relief and
      benign conditions are often self-limiting.

PMID- 22584484
TI  - [Radiology of the adrenal glands].
AB  - An important principle of diagnostic imaging of the adrenal glands is to
      characterize an adrenal mass as an adenoma using computed tomography (CT) or
      magnetic resonance imaging (MRI) techniques. Most techniques exploit the fact
      that typical adrenal adenomas are lipid-rich so that lipid-poor adenomas,
      however, remain a diagnostic problem. A CT attenuation <= 10 HU, more than 10%
      negative pixels as demonstrated by histogram analysis, an absolute washout of
      more than 60%, a relative washout of more than 40% and a signal drop of more than
      20% in opposed-phase images are characteristic for adrenal adenomas. Endocrine
      dysfunction is diagnosed biochemically and not by means of imaging but are
      necessary to localize a functioning tumor. An important principle is to combine
      anatomical with functional imaging studies. Percutaneous biopsy of adrenal glands
      is only indicated when an adrenal mass is the only potential metastasis of a
      diagnosed primary tumor.

PMID- 22584486
TI  - Use of FDG PET/CT for investigation of febrile neutropenia: evaluation in high
      risk cancer patients.
AB  - PURPOSE: Febrile neutropenia (FNP) is a frequent complication of cancer care and
      evaluation often fails to identify a cause. [(18) F]FDG PET/CT has the potential
      to identify inflammatory and infectious foci, but its potential role as an
      investigation for persistent FNP has not previously been explored. The aim of
      this study was to prospectively evaluate the clinical utility of FDG PET/CT in
      patients with cancer and severe neutropenia and five or more days of persistent
      fever despite antibiotic therapy. METHODS: Adult patients with a diagnosis of an
      underlying malignancy and persistent FNP (temperature >=38 degrees C and
      neutrophil count <500 cells/MUl for 5 days) underwent FDG PET/CT as an adjunct to
      conventional evaluation and management. RESULTS: The study group comprised 20
      patients with FNP who fulfilled the eligibility criteria and underwent FDG PET/CT
      in addition to conventional evaluation. The median neutrophil count on the day of
      the FDG PET/CT scan was 30 cells/MUl (range 0-730 cells/MUl). Conventional
      evaluation identified 14 distinct sites of infection, 13 (93 %) of which were
      also identified by FDG PET/CT, including all deep tissue infections. FDG PET/CT
      identified 9 additional likely infection sites, 8 of which were subsequently
      confirmed as "true positives" by further investigations. FDG PET/CT was deemed to
      be of 'high' clinical impact in 15 of the 20 patients (75 %). CONCLUSION: This
      study supports the utility of FDG PET/CT scanning in severely neutropenic
      patients with five or more days of fever. Further evaluation of the contribution
      of FDG PET/CT in the management of FNP across a range of underlying malignancies
      is required.

PMID- 22584488
TI  - Heterometallic coordination polymers incorporating dipyrrin based heteroleptic
      copper and cobalt complexes: to Ag-pi or not?
AB  - Using ligands based on either an acetylacetonate or a dipyrrin moiety appended
      with pyridyl groups, a series of novel heteroleptic copper(II) and cobalt(III)
      complexes combining both chelate units such as (acacpy(2))Cu(dpm-py) and
      (acacpy(2))Co(dpm-py)(2) (acacpy(2) = 1,3-bis(4-pyridyl)-1,3-propanedionate; dpm
      py = 5-(4-pyridyl)dipyrrin) have been prepared and fully characterized. These two
      complexes were obtained upon reaction of dpm-py with the (acacpy(2))M homoleptic
      species (M = Cu(II), Co(II)). In the solid state, the (acacpy(2))Cu(dpm-py)
      complex behaves as a self-complementary metallatecton and leads to the formation
      of a 1D coordination polymer (CP) through the coordination of a peripheral
      pyridyl group to the copper centre. Contrastingly, the octahedral
      (acacpy(2))Co(dpm-py)(2) complex featuring a coordinatively saturated Co(III)
      centre crystallizes as an isolated mononuclear species. In order to generate
      heterometallic CPs, both complexes have been used as metallatectons upon their
      combination with different silver(I) salts. Upon reaction of (acacpy(2))Cu(dpm
      py) with Ag(BF(4)) or Ag(TfO), 2- and 3-D heterometallic networks were obtained,
      respectively. In both cases, sheet type arrangements resulting from the binding
      of Ag(+) cations by three peripheral pyridyl groups were observed. These 2D
      sheets are further interconnected through Ag-pi interactions with the pyrrolic
      rings. Under the same conditions, the combination of (acacpy(2))Co(dpm-py)(2)
      with Ag(TfO) leads to two networks differing by their connectivity patterns and
      dimensionality. Interestingly, whereas no Ag-pi interactions were observed for
      the 2D network, a combination of coordination bonding with the pyridyl moieties
      and Ag-pi interactions was detected for the 1D architecture.

PMID- 22584487
TI  - Is 68Ga-DOTA-NOC PET/CT indicated in patients with clinical, biochemical or
      radiological suspicion of neuroendocrine tumour?
AB  - PURPOSE: In recent years, (68)Ga-DOTA-peptides positron emission tomography
      (PET)/CT has been increasingly used to study patients with neuroendocrine tumours
      (NET). However, performing specialized examinations in the appropriate contest is
      mandatory for both medical and economic reasons. The aim of the study is to
      evaluate the potential usefulness of (68)Ga-DOTA-NOC PET/CT in patients with
      suspected NET. METHODS: Among the patients undergoing (68)Ga-DOTA-NOC PET/CT at
      our centre, we reviewed those studied for suspected NET based on the presence of
      either clinical signs/symptoms or imaging or raised biochemical markers or a
      combination of these conditions. PET/CT results were compared with clinical and
      imaging follow-up of at least 1 year or pathology. RESULTS: Overall 131 suspected
      NET cases were included. The most common condition considered suspicious for NET
      was the increase of blood markers (66), followed by inconclusive findings at
      conventional imaging (CI, 41), clinical signs/symptoms (10), equivocal (18)F
      fluorodeoxyglucose (FDG) PET (7) or somatostatin receptor scintigraphy (SRS, 4),
      or a combination of the above (3). PET/CT results were true-positive in 17 cases,
      true-negative in 112 and false-negative in 2 (overall sensitivity 89.5 %,
      specificity 100 %). Interestingly, increased blood markers and clinical
      signs/symptoms were associated with the lowest frequency of true-positive
      findings (1/66 and 1/10, respectively), while CI findings were confirmed in one
      third of the cases (13/41). Overall, the incidence of NET in the studied
      population was 14.5 % (19/131). CONCLUSION: Our data confirm the good accuracy
      (98 %) of (68)Ga-DOTA-NOC PET/CT in NET lesion detection. However, our results
      also suggest that (68)Ga-DOTA-NOC PET/CT may not be routinely recommended in
      patients with a suspicion of NET based on the mere detection of increased blood
      markers or clinical symptoms. Positive CI alone or in association with
      clinical/biochemical findings is on the contrary associated with a higher
      probability of true-positive findings.

PMID- 22584489
TI  - Telogen effluvium following bivalent human papillomavirus vaccine administration:
      a report of two cases.
AB  - We describe two cases of telogen effluvium occurring in two 11-year-old children
      following bivalent human papillomavirus (HPV) vaccine administration. The two
      children began to lose their hair following the second HPV vaccine dose. Alopecia
      worsened following the third vaccine dose and then resolved spontaneously within
      a few months. In both cases, laboratory analysis and psychiatric evaluation
      excluded causes other than anti-HPV vaccine. Social discomfort and isolation were
      associated with alopecia in the two children. The clinical presentation was
      consistent with a pattern of telogen effluvium. The identification of specific
      vaccine components responsible for triggering the adverse event remains
      difficult. In similar cases, suspension of immunization is not recommended, as it
      provides health benefits that overcome the possible adverse effect of transient
      telogen effluvium. Caregivers should ensure psychiatric support to their patients
      to manage the social and emotional distress that might be associated with hair
      loss.

PMID- 22584490
TI  - Radiofrequency ablation of childhood arrhythmia: observational registry in 125
      children.
AB  - BACKGROUND: Radiofrequency ablation (RFA) in children is an increasingly common
      practice. OBJECTIVE: To evaluate, in our institution, the results of RFA in
      children younger than 15 years. METHODS: A total of 125 children submitted to RFA
      between May 1991 and May 2010 were analyzed. RESULTS: Sixty-seven (53.6%)
      children were males, aged between 44 days and 15 years (mean 8.6 +/- 3.3 years)
      with median weight of 31 kg. Heart disease was present in 21 (16.8%) patients.
      The RFA of accessory pathways (AP) was the most common procedure (62 children -
      49.6%). The RFA of nodal reentrant tachycardia (NRT) was the second most common
      arrhythmia in 27 (21.6%), followed by atrial tachycardia (AT) in 16 (12.8%) and
      ventricular tachycardias (VT) in 8 (6.4%) children. The success criteria were
      achieved in 86.9%, 96.1%, 80% and 62.5% of patients undergoing RFA of AP, NRT, AT
      and VT, respectively. Transient AVB occurred during RFA in 4 (3.2%) and LBBB in 7
      (5.6%) children. Twenty-five children underwent a new RFA due to initial failure
      or recurrence. During the mean follow up of 5.5 +/- 3.4 years, 107 (88.4%)
      remained without recurrence. There was no statistical difference regarding the
      results and the age at which the patient underwent the procedure. No child had
      persistent AVB or required a permanent pacemaker. CONCLUSION: Catheter ablation
      is a safe and effective alternative therapy in children with recurrent
      tachycardias refractory to medical treatment.

PMID- 22584491
TI  - Successful improvement of frequency and symptoms of premature complexes after
      oral magnesium administration.
AB  - BACKGROUND: Premature ventricular and supraventricular complexes (PVC and PsVC)
      are frequent and often symptomatic. The magnesium (Mg) ion plays a role in the
      physiology of cell membranes and cardiac rhythm. OBJECTIVE: We evaluated whether
      the administration of Mg Pidolate (MgP) in patients with PVC and PsVC is superior
      to placebo (P) in improving symptoms and arrhythmia frequency. METHODS:
      Randomized double-blind study with 60 consecutive symptomatic patients with more
      than 240 PVC or PsVC on 24-hour Holter monitoring who were selected to receive
      placebo (P) or MgP. To evaluate symptom improvement, a categorical and a specific
      questionnaire for symptoms related to PVC and PsVC was made. Improvement in
      premature complex density (PCD) per hour was considered significant if percentage
      reduction was >70% after treatment. The dose of MgP was 3.0 g/day for 30 days,
      equivalent to 260 mg of Mg element. Any patient had structural heart disease or
      renal failure. RESULTS: Of the 60 patients, 33 were female (55%). Ages ranged
      from 16 to 70 years old. In the MgP group, 76.6% of patients had a PCD reduction
      >70%, 10% of them >50% and only 13.4% <50%. In the P group, 40% showed slight
      improvement, <30%, in the PC frequency (p < 0.001). Symptom improvement was
      achieved in 93.3% of patients in the MgP group, compared with only 16.7% in the P
      group (p < 0.001). CONCLUSION: Oral Mg supplementation decreases PCD, resulting
      in symptom improvement.

PMID- 22584492
TI  - Left atrial appendage closure with the Amplatzer cardiac plug in patients with
      atrial fibrillation.
AB  - BACKGROUND: Percutaneous left atrial appendage closure (LAAC) has emerged as an
      alternative to oral anticoagulation (OA) for prevention of thromboembolic stroke
      in patients with non-valvular atrial fibrillation (NVAF). OBJECTIVE: To describe
      the immediate results and short- to medium-term clinical follow-up (FU) of
      patients that underwent LAAC with Amplatzer Cardiac Plug (ACP) implantation in a
      single reference center. METHODS: Eighty-six consecutive patients with NVAF,
      contraindication to OA, and CHADS2 score=2.6 +/- 1.2 underwent LAAC with ACP
      implantation. Clinical and echocardiographic FU was performed at least four
      months after the procedure. RESULTS: All implants were guided by angiography
      alone. Procedural success was 99% (one patient suffered a cardiac tamponade
      requiring pericardiocentesis, and the procedure was waived). There were four
      major complications (the already mentioned cardiac tamponade, two transient
      ischemic attacks and one device embolization with percutaneous retrieval) and two
      minor complications (one pericardial effusion without clinical significance and
      one non-significant ASD evidenced at FU). There was one in-hospital death after
      six days, unrelated to the procedure. All other patients were discharged without
      OA. After 25.9 patient-years of FU (69 patients), there were no strokes and no
      late device embolization. The LAA was completely closed in 97% of the cases. Six
      patients showed evidence of thrombus formation on the device, which resolved
      after three months of OA. CONCLUSION: LAAC is associated with high success,
      acceptable complication rates, and promising FU results, and may be considered a
      valuable alternative or complement to OA for stroke prevention in patients with
      NVAF.

PMID- 22584493
TI  - Causality analysis of the relationship between bleeding and lethality in Acute
      Coronary Syndromes.
AB  - BACKGROUND: Hemorrhagic events in Acute Coronary Syndromes (ACS) have been
      independently associated with death in international multicenter registries.
      However, that association has not been tested in Brazil and the true causal
      relationship between bleeding and death has not been completely shown. OBJECTIVE:
      To test the following hypotheses: (1) major bleeding is an independent predictor
      of in-hospital death in ACS; (2) the relationship between those two endpoints is
      causal. METHODS: This study included patients meeting predefined criteria of
      unstable angina, non-ST-segment elevation myocardial infarction or ST-segment
      elevation myocardial infarction. Major bleeding during hospitalization was
      defined according to the Bleeding Academic Research Consortium (types 3 or 5).
      Logistic regression and analysis of the sequence of events were used to assess
      the association between bleeding and death. RESULTS: Of the 455 patients studied,
      29 experienced major bleeding (6.4%; 95% CI = 4.3-9.0%). They had in-hospital
      mortality of 21%, as compared with 5.6% of those not experiencing bleeding (RR =
      4.0; 95% CI = 1.8-9.1; P = 0.001). After adjusting for the propensity score,
      major bleeding remained as a predictor of in-hospital death (OR = 3.34; 95% CI =
      1.2-9.5; P = 0.02). Of the 29 patients who experienced bleeding, six died.
      However, the detailed analysis of the sequence of events showed causal
      relationship only in one case. CONCLUSION: (1) Major bleeding is an independent
      predictor of in-hospital death in ACS; (2) the role of bleeding as a risk marker
      overcomes that as a risk factor for death. This conclusion should be seen as a
      hypothesis generator to be confirmed by larger-sample studies.

PMID- 22584494
TI  - Increased intima-media thickness is independently associated with ischemic
      stroke.
AB  - BACKGROUND: Stroke is one of the major causes of death worldwide. The importance
      of increased intima-media thickness in cardiovascular risk stratification has
      been recurrently studied. The relationship between them, however, is still
      controversial. OBJECTIVES: To determine whether increased common carotid artery
      (CCA) intima-media thickness can be used as an independent high-risk marker for
      the occurrence of stroke. METHODS: This study sample comprised 948 patients
      consecutively assessed by use of cervical triplex scan from January 2004 to June
      2009. Those patients were divided into groups according to the presence or
      absence of recent stroke as follows: a group of patients with ischemic stroke (n
      = 452, 48%); a group of patients with hemorrhagic stroke (n = 22, 2%); and a
      group of patients with no events (n = 474, 50%). RESULTS: On logistic regression
      analysis adjusted for the classic cardiovascular risk factors, increased CCA
      intima-media thickness associated significantly and on an approximately linear
      way with ischemic stroke (Odds Ratio = 1.808, confidence interval: 1.291-2.534, p
      = 0.01), but not with hemorrhagic stroke (p = ns). A significant interaction with
      age was also found, showing a greater discriminative capacity for the risk of
      ischemic stroke in individuals aged less than 50 years. CONCLUSIONS: The
      increased CCA intima-media thickness was identified as an independent predictor
      of the risk for ischemic stroke, but not for hemorrhagic stroke, emphasizing the
      usefulness of its assessment on clinical practice.

PMID- 22584498
TI  - Cicatricial Alopecia Symposium 2011: Lipids, inflammation and stem cells.

PMID- 22584499
TI  - Topical tretinoin, another failure in the pursuit of practical chemoprevention
      for non-melanoma skin cancer.
AB  - Given the high incidence of non-melanoma skin cancer (NMSC), a preventative
      intervention would be desirable. Except for regular sunscreen use, the quest for
      chemoprevention of NMSC in the general population has been unsuccessful.
      Weinstock et al. assessed the effects of 0.1% topical tretinoin on NMSC. Like
      earlier efforts at chemoprevention, this study failed to show therapeutic
      benefit. Future successful preventative strategies will likely rely on short
      term, intermittent therapy or treatments used for other common indications.

PMID- 22584500
TI  - Capturing the finer points of gene expression in psoriasis: beaming in on the
      CCL19/CCR7 axis.
AB  - Laser capture microdissection-coupled complementary DNA microarray analysis is a
      powerful tool for studying minor cell populations in tissues. In this issue,
      Mitsui et al. use this method to characterize the immune infiltrates that
      localize in the dermis of psoriatic skin. They identify the T-cell activation
      regulators C-C chemokine ligand 19 and C-C chemokine receptor 7 as potential
      mediators of immune organization in psoriasis.

PMID- 22584501
TI  - Stem cells in tissue repair and regeneration.
AB  - The field of tissue repair and wound healing has blossomed in the past 30 years.
      We have gone from recombinant growth factors, to living tissue engineering
      constructs, to stem cells. The task now is to pursue true regeneration, thus
      achieving complete restoration of structure and function.

PMID- 22584502
TI  - Targeting the palm: a leap forward toward treatment of keratin disorders.
AB  - Any rational therapy benefits from an understanding of basic biology and the
      simplicity of its strategy. Among keratinopathies, epidermolytic palmoplantar
      keratoderma stands out by virtue of hotspot mutations in the KRT9 gene,
      exclusively expressed in the palmoplantar epidermis. In this issue, Leslie
      Pedrioli et al. report on the successful application of KRT9-specific siRNAs in
      cultured cells and in a mouse model. The study beautifully illustrates the
      potency of a thorough experimental approach and the challenges that remain,
      especially in its delivery.

PMID- 22584504
TI  - Synthesis, interface (Au/M2Pc2/p-Si), electrochemical and electrocatalytic
      properties of novel ball-type phthalocyanines.
AB  - The phthalodinitrile derivative (3) was prepared by the reaction of 4,4'
      (octahydro-4,7-methano-5H-inden-5-ylidene)bisphenol (1) and 4-nitrophthalonitrile
      (2) with dry DMF as the solvent in the presence of the base K(2)CO(3) by the
      method of nucleophilic substitution of an activated nitro group in an aromatic
      ring. The template reaction of 3 with the corresponding metal salts gave the
      novel bi-nuclear ball-type metallophthalocyanines, MPcs {M = Co (4), Cu (5), Zn
      (6)}. Newly synthesized compounds were characterized by elemental analysis, UV
      vis, FT-IR (ATR), MALDI-TOF mass and (1)H-NMR spectroscopy techniques. The
      electronic spectra exhibit an intense pi->pi* transition of characteristic Q and
      B bands of the Pc core. The dielectric properties and interface between the spin
      coated films of 4-6 and a p-type silicon substrate have been studied by
      fabricating metal-insulator-semiconductor capacitors. The results indicated that
      the frequency dependence of the dielectric permittivity, epsilon'(omega),
      exhibits non-Debye type relaxation for all the temperatures investigated. The ac
      conductivity results indicated that the conduction mechanism can be explained by
      a hopping model at low temperatures (<430 K) and a free band conduction mechanism
      at high temperatures (>=430 K). The density of interface state calculations on
      these novel compounds showed that the combination of Au/4/p-Si is a promising
      structure with a high dielectric constant and a low interface trap density
      suitable for metal-oxide-semiconductor devices. The electrochemical properties of
      the Pc complexes were examined by cyclic voltammetry, differential voltammetry
      and controlled potential coulometry on platinum in non-aqueous media. The
      complexes showed ring-based and/or metal-based mixed-valence behaviours as a
      result of the remarkable interaction between the two Pc rings and/or metal
      centres. The mixed-valence splitting values for the complexes suggested that the
      mixed valence species are considerably stable. The Vulcan XC-72(VC)/Nafion(Nf)/4
      modified glassy carbon electrode showed much a higher catalytic performance
      towards oxygen reduction than those of VC/Nf/5 and VC/Nf/6 modified ones.

PMID- 22584503
TI  - Mutation analysis of NPHS1 in a worldwide cohort of congenital nephrotic syndrome
      patients.
AB  - BACKGROUND: Congenital nephrotic syndrome (CNS) is defined as nephrotic syndrome
      that manifests within the first 3 months of life. Mutations in the NPHS1 gene
      encoding nephrin, are a major cause for CNS. Currently, more than 173 different
      mutations of NPHS1 have been published as causing CNS, affecting most exons.
      METHODS: We performed mutation analysis of NPHS1 in a worldwide cohort of 20
      families (23 children) with CNS. All 29 exons of the NPHS1 gene were examined
      using direct sequencing. New mutations were confirmed by demonstrating their
      absence in 96 healthy control individuals. RESULTS: We detected disease-causing
      mutations in 9 of 20 families (45%). Seven of the families showed a homozygous
      mutation, while two were compound heterozygous. In another 2 families, single
      heterozygous NPHS1 mutations were detected. Out of 10 different mutations
      discovered, 3 were novel, consisting of 1 splice site mutation and 2 missense
      mutations. CONCLUSION: Our data demonstrate that the spectrum of NPHS1 mutations
      is still expanding, involving new exons, in patients from a diverse ethnic
      background.

PMID- 22584506
TI  - Inhibition of RhoA/ROCK signaling pathway promotes the apoptosis of gastric
      cancer cells.
AB  - BACKGROUND/AIMS: Ras homologue A (RhoA) plays a crucial role in the
      proliferation, apoptosis,adhesion and migration of gastric cancer cells. Rho
      associated kinase (ROCK) is an effector protein of RhoA. METHODOLOGY: In the
      present study, RhoA activity was inhibited by siRNA targeting RhoA andY-27632, an
      inhibitor of ROCK, and the role of RhoA/ROCK signaling pathway in the apoptosis
      of gastric cancer cells was investigated. RESULTS: RNAi of RhoA inhibited the
      survival and promoted the apoptotic of AGS cells. RhoA RNAi caused an obvious
      decrease of ROCK1 expression but an increase of caspase-3/cleaved-caspase-8.
      Inhibition of ROCK by Y-27632 inhibited the activity of RhoA and promoted the
      apoptosis. CONCLUSIONS: We speculate that RhoA/ROCK signaling pathway plays an
      important role in the regulation of apoptosis of gastric cancer, and to inhibit
      this pathway may promote the apoptosis of cancer cells. Thus, inhibition of
      RhoA/ROCK signaling pathway may become a novel target in the treatment of gastric
      cancer.

PMID- 22584505
TI  - Diversity in pathways to common childhood disruptive behavior disorders.
AB  - Oppositional-Defiant Disorder (ODD) and Attention-Deficit/Hyperactivity Disorder
      (ADHD) are highly comorbid, a phenomenon thought to be due to shared etiological
      factors and mechanisms. Little work has attempted to chart multiple-level-of
      analysis pathways (i.e., simultaneously including biological, environmental, and
      trait influences) to ODD and ADHD, the goal of the present investigation. 559
      children/adolescents (325 boys) between the ages of 6 and 18 participated in a
      multi-stage, comprehensive diagnostic procedure. 148 were classified as ODD; 309
      were classified as ADHD, based on parent, teacher, and clinician ratings.
      Children provided buccal or salivary samples of DNA, assayed for select markers
      in DRD4 and 5HTT. Parents completed the Alabama Parenting Questionnaire and the
      California Q-Sort. Children completed the Child Perception of Interparental
      Conflict Scale. Correlational associations consistent with multiple-level-of
      analysis pathways to ODD and ADHD emerged. For ODD, children with the short
      allele of the 5HTT promoter polymorphism had higher neuroticism and ODD symptoms
      regardless of level of self-blame in relation to inter-parental conflict, whereas
      children without this allele had more ODD symptoms only in the context of more
      self-blame for inter-parental conflict. For ADHD (and ODD), children homozygous
      for the long allele of DRD4 120 bp insertion polymorphism had lower
      conscientiousness when exposed to inconsistent parenting, whereas children
      without this genotype were more resilient to effects of inconsistent discipline
      on conscientiousness. Thus, ODD and ADHD appear to demonstrate somewhat distinct
      correlational associations between etiological factors and mechanisms consistent
      with pathway models using a multiple-level-of-analysis approach.

PMID- 22584508
TI  - Different vascular permeability between the sensory and secretory
      circumventricular organs of adult mouse brain.
AB  - The blood-brain barrier (BBB) prevents free access of circulating molecules to
      the brain and maintains a specialized brain environment to protect the brain from
      blood-derived bioactive and toxic molecules; however, the circumventricular
      organs (CVOs) have fenestrated vasculature. The fenestrated vasculature in the
      sensory CVOs, including the organum vasculosum of lamina terminalis (OVLT),
      subfornical organ (SFO) and area postrema (AP), allows neurons and astrocytes to
      sense a variety of plasma molecules and convey their information into other brain
      regions and the vasculature in the secretory CVOs, including median eminence (ME)
      and neurohypophysis (NH), permits neuronal terminals to secrete many peptides
      into the blood stream. The present study showed that vascular permeability of low
      molecular-mass tracers such as fluorescein isothiocyanate (FITC) and Evans Blue
      was higher in the secretory CVOs and kidney as compared with that in the sensory
      CVOs. On the other hand, vascular permeability of high-molecular-mass tracers
      such as FITC-labeled bovine serum albumin and Dextran 70,000 was lower in the
      CVOs as compared with that in the kidney. Prominent vascular permeability of low-
      and high-molecular-mass tracers was also observed in the arcuate nucleus. These
      data demonstrate that vascular permeability for low-molecular-mass molecules is
      higher in the secretory CVOs as compared with that in the sensory CVOs, possibly
      for large secretion of peptides to the blood stream. Moreover, vascular
      permeability for high-molecular-mass tracers in the CVOs is smaller than that of
      the kidney, indicating that the CVOs are not totally without a BBB.

PMID- 22584507
TI  - The importance of clinical information in patients with gastroenteropancreatic
      neuroendocrine tumor.
AB  - BACKGROUND/AIMS: The WHO 2010 grading system for gastroenteropancreatic
      neuroendocrine tumors(GEP-NETs) is used to evaluate the malignant potential
      without clinicopathological information. This study was conducted to examine
      whether the new index is superior to the previous WHO 2004 classification,
      e.g.for well-differentiated endocrine carcinoma (WEC),involving clinical
      information. METHODOLOGY: Between 2000 and 2011, 77 patients with sporadic GEP
      NETs were treated at our institution and statistically estimated risk factors for
      overall survival (OS) were evaluated. Cox proportional hazards regression
      analyses were performed to estimate risk factors for OS. RESULTS: Overall 1-, 3-
      and 5-year survival rates were 92.8%, 78.4% and 76.0%, respectively. Median OS
      was 551 days in WEC-patients (odds ratio (OR)for OS=13.1, 95% confidence interval
      (CI)=2.90-59.5;p=0.001). The median OS was 813 days in G3-patients as compared
      with 1885 days in G1/G2-patients(OR for OS= 2.64, p=0.002). Multivariate analyses
      according to baseline characteristics revealed WEC as independent risk factor
      (OR=9.06, p=0.01). WEC was the only predictor of prognosis with an area under the
      receiver operating characteristic curves of 0.78(p=0.001). CONCLUSIONS: Clinical
      information was the best predictor for the prognosis of NETs.

PMID- 22584509
TI  - Community-based participatory process--climate change and health adaptation
      program for Northern First Nations and Inuit in Canada.
AB  - OBJECTIVES: Health Canada's Program for Climate Change and Health Adaptation in
      Northern First Nation and Inuit Communities is unique among Canadian federal
      programs in that it enables community-based participatory research by northern
      communities. STUDY DESIGN: The program was designed to build capacity by funding
      communities to conduct their own research in cooperation with Aboriginal
      associations, academics, and governments; that way, communities could develop
      health-related adaptation plans and communication materials that would help in
      adaptation decision-making at the community, regional, national and circumpolar
      levels with respect to human health and a changing environment. METHODS:
      Community visits and workshops were held to familiarize northerners with the
      impacts of climate change on their health, as well as methods to develop research
      proposals and budgets to meet program requirements. RESULTS: Since the launch of
      the Climate Change and Health Adaptation Program in 2008, Health Canada has
      funded 36 community projects across Canada's North that focus on relevant health
      issues caused by climate change. In addition, the program supported capacity
      building workshops for northerners, as well as a Pan-Arctic Results Workshop to
      bring communities together to showcase the results of their research. Results
      include: numerous films and photo-voice products that engage youth and elders and
      are available on the web; community-based ice monitoring, surveillance and
      communication networks; and information products on land, water and ice safety,
      drinking water, food security and safety, and traditional medicine. CONCLUSIONS:
      Through these efforts, communities have increased their knowledge and
      understanding of the health effects related to climate change and have begun to
      develop local adaptation strategies.

PMID- 22584510
TI  - Being useful: achieving indigenous youth involvement in a community-based
      participatory research project in Alaska.
AB  - OBJECTIVES: To report on a participatory research process in southwest Alaska
      focusing on youth involvement as a means to facilitate health promotion. We
      propose youth-guided community-based participatory research (CBPR) as way to
      involve young people in health promotion and prevention strategizing as part of
      translational science practice at the community-level. STUDY DESIGN: We utilized
      a CBPR approach that allowed youth to contribute at all stages. METHODS:
      Implementation of the CBPR approach involved the advancement of three key
      strategies including: (a) the local steering committee made up of youth, tribal
      leaders, and elders, (b) youth-researcher partnerships, and (c) youth action
      groups to translate findings. RESULTS: The addition of a local youth-action and
      translation group to the CBPR process in the southwest Alaska site represents an
      innovative strategy for disseminating findings to youth from a research project
      that focuses on youth resilience and wellbeing. This strategy drew from two
      community-based action activities: (a) being useful by helping elders and (b)
      being proud of our village. CONCLUSIONS: In our study, youth informed the
      research process at every stage, but most significantly youth guided the
      translation and application of the research findings at the community level.
      Findings from the research project were translated by youth into serviceable
      action in the community where they live. The research created an experience for
      youth to spend time engaged in activities that, from their perspectives, are
      important and contribute to their wellbeing and healthy living. Youth-guided CBPR
      meant involving youth in the process of not only understanding the research
      process but living through it as well.

PMID- 22584511
TI  - Challenges created by data dissemination and access restrictions when attempting
      to address community concerns: individual privacy versus public wellbeing.
AB  - BACKGROUND: Population health data are vital for the identification of public
      health problems and the development of public health strategies. Challenges arise
      when attempts are made to disseminate or access anonymised data that are deemed
      to be potentially identifiable. In these situations, there is debate about
      whether the protection of an individual's privacy outweighs potentially
      beneficial public health initiatives developed using potentially identifiable
      information. While these issues have an impact at planning and policy levels,
      they pose a particular dilemma when attempting to examine and address community
      concerns about a specific health problem. METHODS: Research currently underway in
      northern Canadian communities on the frequency of Helicobacter pylori infection
      and associated diseases, such as stomach cancer, is used in this article to
      illustrate the challenges that data controls create on the ability of researchers
      and health officials to address community concerns. RESULTS: Barriers are faced
      by public health professionals and researchers when endeavouring to address
      community concerns; specifically, provincial cancer surveillance departments and
      community-driven participatory research groups face challenges related to data
      release or access that inhibit their ability to effectively address community
      enquiries. The resulting consequences include a limited ability to address
      misinformation or to alleviate concerns when dealing with health problems in
      small communities. CONCLUSIONS: The development of communication tools and
      building of trusting relationships are essential components of a successful
      investigation into community health concerns. It may also be important to
      consider that public wellbeing may outweigh the value of individual privacy in
      these situations. As such, a re-evaluation of data disclosure policies that are
      applicable in these circumstances should be considered.

PMID- 22584512
TI  - Youth researching youth: benefits, limitations and ethical considerations within
      a participatory research process.
AB  - OBJECTIVES: To examine the benefits, limitations and ethical issues associated
      with conducting participatory research on tobacco use using youth to research
      other youth. STUDY DESIGN: Community-based participatory research. METHODS:
      Research on tobacco use was conducted with students in the K'alemi Dene School
      and Kaw Tay Whee School in the Northwest Territories, Canada, using PhotoVoice.
      The Grade 9-12 students acted as researchers. Researcher reflections and
      observations were assessed using "member checking," whereby students, teachers
      and community partners could agree or disagree with the researcher's
      interpretation. The students and teachers were further asked informally to share
      their own reflections and observations on this process. RESULTS AND CONCLUSIONS:
      Using youth to research other youth within a participatory research framework had
      many benefits for the quality of the research, the youth researchers and the
      community. The research was perceived by the researchers and participants to be
      more valid and credible. The approach was more appropriate for the students, and
      the youth researchers gained valuable research experience and a sense of
      ownership of both the research process and results. Viewing smoking through their
      children's eyes was seen by the community to be a powerful and effective means of
      creating awareness of the community environment. Limitations of the approach were
      residual response bias of participants, the short period of time to conduct the
      research and failure to fully explore student motivations to smoke or not to
      smoke. Ethical considerations included conducting research with minors,
      difficulties in obtaining written parental consent, decisions on cameras
      (disposable versus digital) and representation of all participants in the final
      research product.

PMID- 22584513
TI  - Association between socioeconomic status and overweight and obesity among Inuit
      adults: International Polar Year Inuit Health Survey, 2007-2008.
AB  - OBJECTIVES: To evaluate the socio-economic correlates of overweight and obesity
      among Inuit undergoing rapid cultural changes. STUDY DESIGN: A cross-sectional
      health survey of 2,592 Inuit adults from 36 communities in the Canadian Arctic.
      METHODS: Main outcome measures were overweight and obesity (BMI>25 kg/m2 and >30
      kg/m2, respectively) and as characteristics were similar, groups were combined
      into an at-risk BMI category (BMI>25 kg/m2). Logistic regression was used to
      determine the association between various sociodemographic characteristics and
      physical activity with overweight and obesity. RESULTS: The prevalence of
      overweight and obesity was 28 and 36%, respectively, with a total prevalence of
      overweight and obesity of 64%. In analyses of sociodemographic variables adjusted
      for age, gender and region, higher education, any employment, personal income,
      and private housing were all significantly positively correlated with an at-risk
      BMI (p<=0.001). Smoking, Inuit language as primary language spoken at home, and
      walking were inversely associated with overweight and obesity. CONCLUSIONS: The
      current findings highlight the social disparities in overweight and obesity
      prevalence in an ethnically distinct population undergoing rapid cultural
      changes.

PMID- 22584514
TI  - Against the stream: relevance of gluconeogenesis from fatty acids for natives of
      the arctic regions.
AB  - BACKGROUND: The question whether even-chain fatty acids can be converted into
      glucose has a long-standing tradition in biochemistry. Since the glyoxylate shunt
      is absent from mammals, the question has been considered to be solved. It is of
      particular relevance for understanding the metabolic state of natives of the
      arctic regions due to the very high fat content of their traditional diet only
      containing negligible amounts of carbohydrates. METHODS & RESULTS: Using an in
      silico approach, we discovered several hitherto unknown routes in human
      metabolism that allow the conversion of even-chain fatty acids into carbohydrates
      in humans. These pathways proceed via ketogenesis over the intermediate of
      acetone and produce the gluconeogenic precursor pyruvate. While these pathways
      can make a contribution to glucose production during times of limited
      carbohydrate supply, we found that their capacity might be limited due to a high
      demand in reducing equivalents in acetone degradation. Considering the
      traditional diet of natives of the arctic regions, the detected pathways are not
      only important in order to improve carbohydrate supply, but moreover reduce the
      amount of protein that needs to be used for gluconeogenesis. CONCLUSION: In
      summary, our study sheds new light on our understanding of the metabolic state of
      natives from the arctic regions on their traditional diet. Moreover, they provide
      an avenue for new analyses that can reveal how humans have adapted metabolically
      to a practically carbohydrate-free diet.

PMID- 22584515
TI  - How occupational health is assessed in mine workers in Murmansk Oblast.
AB  - OBJECTIVES: We aimed to describe how work exposure and occupational health is
      assessed for mine workers in Murmansk Oblast, Russia. STUDY DESIGN: A descriptive
      study based on current practice, laws and available literature. METHODS: The
      information and data were obtained from scientific publications, reports,
      regional and federal statistics, legal documents, through personal visits and on
      site inspections. RESULTS: Several institutions are involved in these
      assessments, but all mine workers have been examined by specialists at one
      institution, which helps to ensure that the work is of stable quality and adds
      reliability value to the numbers. Workplace risks are assigned hazard grades,
      which influence the frequency of periodic medical examinations and salary levels.
      The examinations are aimed to diagnose latent or manifest occupational disease.
      This may lead to relocation to a workplace with lower exposure levels, free
      medical treatment, compensation and a lower pension age. CONCLUSIONS: Regulations
      and systems to protect the health of mine workers have more emphasis on control
      and repair than on prevention. Since relocation can lower the salary, some
      workers may under-report medical problems. To what degree this happens is
      unknown. The mining enterprises pay the medical service provider for periodic
      medical examinations, which could potentially weaken their independent role. This
      framework is important to understand when studying and assessing the health of
      working populations in the circumpolar region.

PMID- 22584516
TI  - Sense of coherence and self-reported health among Roma people in Sweden--a pilot
      study.
AB  - OBJECTIVES: The Roma people have been known in Europe for a 1000 years, during
      which they have usually been the subject of discrimination and oppression leading
      to isolation, powerlessness and poor health. The objective of this study is to
      investigate the sense of coherence (SOC) in relation to self-reported health
      among a group of Roma people in southwest Sweden. STUDY DESIGN: A cross
      sectional, quantitative pilot study. METHODS: A questionnaire was constructed
      based on the Short-Form Health Survey (SF-12) and Antonovsky's Sense of Coherence
      Scale (SOC-13) and was distributed among Roma people in southwest Sweden (n
      =102). Self-reported health was summarised in a physical score (PCS) and a mental
      score (MCS). Comparisons were made with a general Swedish majority population and
      a Sami population. RESULTS: The health scores were significantly lower among the
      Roma people compared to Swedes - PCS: Roma 46.0 (Swedes 52.0) and MCS: Roma 47.5
      (Swedes 52.6). The SOC score for the Roma people (54.4) was significantly lower
      than that of the Swedes (65.2) and Sami (65.0). CONCLUSIONS: The low SOC with the
      Swedish majority society is a strong indication of the marginalisation and
      exclusion of the Roma people from mainstream society. Low scores in self-reported
      health among the Roma people also establishes the serious health risks the Roma
      people are experiencing through their present life situation.

PMID- 22584517
TI  - Increasing rates of diabetes amongst status Aboriginal youth in Alberta, Canada.
AB  - OBJECTIVES: To track and compare trends in diabetes rates from 1995 to 2007 for
      Status Aboriginal and general population youth. STUDY DESIGN: Longitudinal
      observational research study (quantitative) using provincial administrative data.
      METHODS: De-identified data was obtained from Alberta Health and Wellness
      administrative databases for Status Aboriginal (First Nations and Inuit people
      with Treaty status) and general population youth (<20 years). Diabetes cases were
      identified using the National Diabetes Surveillance System algorithm. Crude
      annual diabetes prevalence and incidence rates were calculated. The likelihood of
      being a prevalent case and incident case of diabetes for the 2 populations was
      compared for the year 2007. Average Annual Percent Changes (AAPC) in prevalence
      and incidence from 1995 to 2007 were determined and compared between the 2 groups
      to examine trends over time. RESULTS: While the prevalence of diabetes was higher
      in the general population in 1995, by 2007 there were no between group
      differences, reflected in the significantly higher AAPC of 6.98 for Status
      Aboriginal youth. Status Aboriginal males had a lower diabetes risk in 1995
      compared with females, and experienced a greater increase in prevalence over the
      13 years (AAPC 9.18) so that by 2007 their rates were equivalent to those of the
      females. Differences in diabetes incidence trends were only observed among male
      youth, where increases in incidence were greater for Status Aboriginal (AAPC
      11.65) compared to general population males (AAPC 4.62) (p = 0.03). CONCLUSION:
      Youth-onset diabetes is an increasing problem in Alberta, especially among young
      Status Aboriginal males.

PMID- 22584518
TI  - Fatal hypothermia: an analysis from a sub-arctic region.
AB  - OBJECTIVES: To determine the incidence as well as contributing factors to fatal
      hypothermia. STUDY DESIGN: Retrospective, registry-based analysis. METHODS: Cases
      of fatal hypothermia were identified in the database of the National Board of
      Forensic Medicine for the 4 northernmost counties of Sweden and for the study
      period 1992-2008. Police reports, medical records and autopsy protocols were
      studied. RESULTS: A total of 207 cases of fatal hypothermia were noted during the
      study period, giving an annual incidence of 1.35 per 100,000 inhabitants. Seventy
      two percent occurred in rural areas, and 93% outdoors. Many (40%) were found
      within approximately 100 meters of a building. The majority (75%) occurred during
      the colder season (October to March). Some degree of paradoxical undressing was
      documented in 30%. Ethanol was detected in femoral vein blood in 43% of the
      victims. Contributing co-morbidity was common and included heart disease, earlier
      stroke, dementia, psychiatric disease, alcoholism, and recent trauma.
      CONCLUSIONS: With the identification of groups at high risk for fatal
      hypothermia, it should be possible to reduce risk through thoughtful
      interventions, particularly related to the highest risk subjects (rural, living
      alone, alcohol-imbibing, and psychiatric diagnosis-carrying) citizens.

PMID- 22584523
TI  - New tools for old concerns.

PMID- 22584519
TI  - A traditional Sami diet score as a determinant of mortality in a general northern
      Swedish population.
AB  - OBJECTIVES: To examine the relationship between "traditional Sami" dietary
      pattern and mortality in a general northern Swedish population. STUDY DESIGN:
      Population-based cohort study. METHODS: We examined 77,319 subjects from the
      Vasterbotten Intervention Program (VIP) cohort. A traditional Sami diet score was
      constructed by adding 1 point for intake above the median level of red meat,
      fatty fish, total fat, berries and boiled coffee, and 1 point for intake below
      the median of vegetables, bread and fibre. Hazard ratios (HR) for mortality were
      calculated by Cox regression. RESULTS: Increasing traditional Sami diet scores
      were associated with slightly elevated all-cause mortality in men [Multivariate
      HR per 1-point increase in score 1.04 (95% CI 1.01-1.07), p=0.018], but not for
      women [Multivariate HR 1.03 (95% CI 0.99-1.07), p=0.130]. This increased risk was
      approximately equally attributable to cardiovascular disease and cancer, though
      somewhat more apparent for cardiovascular disease mortality in men free from
      diabetes, hypertension and obesity at baseline [Multivariate HR 1.10 (95% CI 1.01
      1.20), p=0.023]. CONCLUSIONS: A weak increased all-cause mortality was observed
      in men with higher traditional Sami diet scores. However, due to the complexity
      in defining a "traditional Sami" diet, and the limitations of our questionnaire
      for this purpose, the study should be considered exploratory, a first attempt to
      relate a "traditional Sami" dietary pattern to health endpoints. Further
      investigation of cohorts with more detailed information on dietary and lifestyle
      items relevant for traditional Sami culture is warranted.

PMID- 22584521
TI  - Decision trees for evaluating skin and respiratory sensitizing potential of
      chemicals in accordance with European regulations.
AB  - Guidance for determining the sensitizing potential of chemicals is available in
      EC Regulation No. 1272/2008 Classification, Labeling, and Packaging of
      Substances; REACH guidance from the European Chemicals Agency; and the United
      Nations Globally Harmonized System (GHS). We created decision trees for
      evaluating potential skin and respiratory sensitizers. Our approach (1) brings
      all the regulatory information into one brief document, providing a step-by-step
      method to evaluate evidence that individual chemicals or mixtures have
      sensitizing potential; (2) provides an efficient, uniform approach that promotes
      consistency when evaluations are done by different reviewers; (3) provides a
      standard way to convey the rationale and information used to classify chemicals.
      We applied this approach to more than 50 chemicals distributed among 11
      evaluators with varying expertise. Evaluators found the decision trees easy to
      use and recipients (product stewards) of the analyses found that the resulting
      documentation was consistent across users and met their regulatory needs. Our
      approach allows for transparency, process management (e.g., documentation, change
      management, version control), as well as consistency in chemical hazard
      assessment for REACH, EC Regulation No. 1272/2008 Classification, Labeling, and
      Packaging of Substances and the GHS.

PMID- 22584524
TI  - Stress and pain associated with dressing change in patients with chronic wounds.
AB  - OBJECTIVE: To assess pain and stress experienced by patients with chronic wounds
      at dressing change and to examine how this may be related to long-term chronic
      stress. METHOD: The study recruited 43 outpatients, with a mean age of 71.7 +/-
      14.6 years. The sample included 18 male (42%) and 25 female (58%) patients from
      Wrexham and Salford (UK), all with chronic wounds that required frequent dressing
      changes. Physiological and psychological measurements of pain and stress,
      including numerical ratings (for stress and pain), heart rate, blood pressure,
      respiration rate, and a questionnaire survey of state and trait anxiety and of
      chronic stress were recorded at dressing change and in a control condition (at
      least 24 hours before/after dressing change during a period of rest). RESULTS:
      Mean heart rate measurements were significantly higher at dressing change, while
      there was also a trend for higher numerical pain ratings, numerical stress
      ratings and state anxiety scores at this time. A significant, positive
      relationship was found between chronic stress and acute episodes of stress
      experienced at dressing change. Similarly, although not significant, a positive
      relationship was observed between chronic stress and acute pain reported at
      dressing change. CONCLUSION: This study provides a basis for understanding how
      increased acute pain and stress at dressing change may be related to chronic
      stress, which has been shown in the literature to contribute to delayed wound
      healing. The impact of these implications on cost of care and quality of life are
      also discussed. DECLARATION OF INTEREST: This study was commissioned by Molnlycke
      Health Care Ltd. None of the authors work for Molnlycke Health Care or have any
      financial interests with the company. There are no additional conflicts of
      interest to declare.

PMID- 22584525
TI  - Workload and prevalence of open wounds in the community: French Vulnus
      initiative.
AB  - OBJECTIVE: To calculate the prevalence of open cutaneous wounds presented on a
      routine working day in community settings in metropolitan France, and to estimate
      the workload associated with the care of these wounds by nurses, GPs and
      specialists (dermatologists, diabetologists and phlebologists). METHOD: A
      transversal epidemiological survey was conducted on a randomly selected sample of
      the above practitioners between June and July 2008. The percentage of patients
      presenting on a routine working day with open a cutaneous lesion of any origin,
      location, size and duration was assessed. All local and systemic care performed
      on the patient during that day because of the wound was also recorded. RESULTS:
      In total, 475 GPs, 453 specialists and 238 nurses participated (n=1166) and saw a
      total of 29 663 patients, of whom 3037 presented with one or more cutaneous
      wound. The overall non-weighted prevalence of patients with a wound was 10.2%
      (95%CI: 9.9%;10.6%). This prevalence was similar for GPs (6.0%) and for
      specialists (6.9%), but was higher for nurses (22.0%). Forty-three per cent of
      all wounds had a duration of over 6 weeks. These chronic wounds were
      predominantly leg ulcers, diabetic foot ulcers or pressure ulcers, but also
      included wounds of all aetiologies. For 33% of all patients with wounds, the
      impact on their health status was serious to severe. The overwhelming majority of
      wounds (95%) required local care, including in 65% of cases cleansing and
      debridement. CONCLUSION: Despite its limitations, this initiative, the first of
      its type in France, strongly suggests that wound care constitutes an important
      part of routine care given by health professionals in the community, and for a
      substantial number of these patients, wounds represent a serious morbidity.
      DECLARATION OF INTEREST: The non-profit organisation 'Association Vivre avec une
      Plaie' financially supported this study. This association received unrestricted
      grants from the French Wound Healing Society (SFFPC) and a consortium of private
      companies (main sponsors: ConvaTec, Genevrier, Hartmann, KCI, Molnycke, Smith &
      Nephew, Urgo; minor sponsors: Coloplast, Covidien, HNE) to fund the costs
      incurred by the methodological process and statistical analysis but had no input
      into the findings. The National Health Insurance Organisation provided non
      financial support to this initiative. J.C. Kerihuel received support for the
      submitted work from 'Association Vivre avec une Plaie'. S. Meaume, I. Fromantin
      and L. Teot have no financial relationship with 'Association Vivre avec une
      Plaie', for either this or any work submitted in the previous 3 years. The
      authors have no non-financial interests that may be relevant to the submitted
      work, and their spouses, partners, or children have no financial relationships
      that may be relevant to the submitted work

PMID- 22584526
TI  - Resynthesis of sternal dehiscence with autologous bone graft and autologous
      platelet gel.
AB  - Postoperative management of sternal dehiscence requires the organised effort of a
      multidisciplinary medical team, including orthopaedic surgeons, plastic surgeons,
      microbiologists, critical care nurses and rehabilitation experts. Clinical care
      of this complication impacts heavily on health-care costs, length of hospital
      stay, and the time to full recovery and return to regular work activity. There
      are various surgical approaches to sternal resynthesis, but they are often
      unsuccessful. In this paper, we describe the case of a 67-year-old male
      complaining of chronic pain due to sternal dehiscence after coronary artery
      bypass grafting surgery. We first report a technique for sternal resynthesis,
      performed in the cardiac surgery setting, using a combination of autologous bone
      graft and autologous platelet-derived gel (APG), and describe its postoperative
      management and outcome. The four-month follow-up was uneventful and a CT scan
      confirmed full healing of the nonunion site with solid bridging bone.

PMID- 22584527
TI  - The use of maggot debridement therapy in the treatment of chronic wounds in
      hospitalised and ambulatory patients.
AB  - OBJECTIVE: To summarise our experience of the use of medicinal maggots for the
      debridement of necrotic chronic wounds and to try and identify prognostic factors
      for debridement success and associated pain. METHOD: During the years 1996-2009,
      723 wounds of 435 patients (180 females and 255 males) were treated with maggot
      debridement therapy (MDT) in 16 departments and units of the Hadassah Hospital in
      Jerusalem, Israel. Overall, 261 patients were treated during hospitalisation,
      while 174 were treated as ambulatory patients. In 90.5% of the patients the
      wounds were located on the leg, but only 48.0% had diabetic foot ulcers. The
      wound duration range from one to 240 months (mean=8.9; median=4 months). Sterile
      maggots of the green bottle fly, Lucilia sericata, were used for MDT. In 90.6% of
      the cases, maggots were placed directly on the wound using a cage-like dressing
      and left for 24 hours, while in 9.4% of the patients maggots concealed in a tea
      bag like polyvinyl netting were used. The concealed maggots were left on the
      wound for 2-3 days. RESULTS: The number of treatments was 1-48 (mean=2.98;
      median=2) and the duration of the treatment varied between one and 81 days
      (mean=4.65; median=3). In 357 patients (82.1%) complete debridement of the wound
      was achieved, while in 73 patients (16.8%) the debridement was partial and in
      five (1.1%) it was ineffective. Increased pain or discomfort during MDT were
      reported in 38% of the patients. CONCLUSION: MDT is a very safe, simple and
      effective treatment modality for chronic wounds in ambulatory and hospitalised
      patients. DECLARATION OF INTEREST: There were no external sources of funding for
      this study. The authors have no additional conflicts of interest to declare.

PMID- 22584528
TI  - The effect of wound dressings on the pH stability of fluids.
AB  - Wound healing is a complex process that is influenced by both intrinsic and
      extrinsic factors, and it is becoming increasingly complex with the latest
      treatment methods and investigations of wound nature. The term 'wound healing'
      covers all types of wounds, burns and ulcerations. There is a considerable global
      variation in the treatment of acute and chronic wounds, therefore, establishing a
      standardised, best way to manage wounds may not be possible. Complete wound
      healing, which includes restoration of function, is hardly ever achieved in those
      disfigured by wounds, especially when one includes the appearance of scarred skin
      or an amputation.

PMID- 22584529
TI  - Efficacy of a silver lipidocolloid dressing on heavily colonised wounds: a
      republished RCT.
AB  - Nearly all open wounds are contaminated by microorganisms. This generally
      corresponds to simple bacterial growth, without leading to deleterious effects or
      compromising the progress of the healing process. In acute wounds, the
      probability of wound infection increases as the level of contamination does.
      However, it is more complex for chronic wounds, which are able to contain and
      tolerate large amounts of bacteria, many times higher than the usual threshold
      level (>105 bacteria/g of tissue) defining infection in acute wounds,1 without
      inducing local signs. Nevertheless, many clinical and experimental studies
      indicate that the probability for chronic wounds to heal properly is limited when
      the bacterial load exceeds this level of contamination; even when body defences
      are still able to prevent tissue invasion, bacteria can impair wound healing.

PMID- 22584530
TI  - A newly identified missense mutation of the HR gene is associated with a novel,
      unusual phenotype of Marie Unna Hereditary Hypotrichosis 1 including limb
      deformities.
AB  - Marie Unna Hereditary Hypotrichosis 1 (MUHH1; OMIM 146550), a rare monogenic
      condition characterized by the development of sparse, twisted hair or complete
      hair loss, is the consequence of mutations located in the hairless (HR) gene. We
      have identified a 68-year-old Hungarian woman affected by alopecia universalis
      and limb deformities of all four extremities. Direct sequencing of the coding
      regions of the HR gene revealed a novel missense mutation in the third exon of
      the HR gene (c.974G/A, p.Gly325Asp). The affected family member carried the
      mutation in a heterozygous form, while the only available, clinically unaffected
      family member (the son of the patient) and the unrelated controls carried the
      wild type sequence. The association between the presence of HR gene mutations and
      the development of alopecia is well-established, however, further studies are
      needed to elucidate the putative role of this novel HR mutation in the
      development of limb deformities.

PMID- 22584531
TI  - Brain-derived neurotrophic factor in primary headaches.
AB  - Brain derived neurotrophic factor (BDNF) is associated with pain modulation and
      central sensitization. Recently, a role of BDNF in migraine and cluster headache
      pathophysiology has been suspected due to its known interaction with calcitonin
      gene-related peptide. Bi-center prospective study was done enrolling four
      diagnostic groups: episodic migraine with and without aura, episodic cluster
      headache, frequent episodic tension-type headache, and healthy individuals. In
      migraineurs, venous blood samples were collected twice: outside and during
      migraine attacks prior to pain medication. In cluster headache patients serum
      samples were collected in and outside cluster bout. Analysis of BDNF was
      performed using enzyme-linked immunosorbent assay technique. Migraine patients
      revealed significantly higher BDNF serum levels during migraine attacks (n = 25)
      compared with headache-free intervals (n = 53, P < 0.01), patients with tension
      type headache (n = 6, P < 0.05), and healthy controls (n = 22, P < 0.001). There
      was no significant difference between patients with migraine with aura compared
      with those without aura, neither during migraine attacks nor during headache-free
      periods. Cluster headache patients showed significantly higher BDNF
      concentrations inside (n = 42) and outside cluster bouts (n = 24) compared with
      healthy controls (P < 0.01, P < 0.05). BDNF is increased during migraine attacks,
      and in cluster headache, further supporting the involvement of BDNF in the
      pathophysiology of these primary headaches.

PMID- 22584533
TI  - Nurse-led central venous catheter insertion: review of 760 procedures performed
      across three hospitals reveals a low rate of complications.

PMID- 22584532
TI  - Mechanism of Ni2+ and NiOH+ interaction with hydroxamic acids in SDS: evaluation
      of the contributions to the equilibrium and rate parameters in the aqueous and
      micellar phase.
AB  - The equilibria and kinetics (stopped-flow) of the binding of Ni(II) to
      salicylhydroxamic acid (SHA) and phenylbenzohydroxamic acid (PBHA) have been
      investigated in aqueous solutions containing SDS micelles. The two ligands are
      fairly distributed between the two pseudophases present, so the binding reaction
      occurs in both phases. The contributions to the total reaction from each phase
      has been evaluated, following a procedure where use is made of the experimentally
      determined partition coefficients of the reactants involved. The mechanism of the
      reaction occurring on the micelle surface has been derived and comparison with
      the mechanism in water shows that the step Ni(2+) + HL ? NiHL(2+) is operative in
      both pseudophases, whereas the step Ni(2+) + L(-)? NiL(+), which is operative in
      water, is replaced in SDS by the step NiOH(+) + HL ? NiL(+). The analysis of the
      equilibrium and of the kinetic data enabled the evaluation of the equilibrium and
      the rate constants of the individual steps taking part in the binding process
      over the micelle surface. Interestingly, the first hydrolysis constant of the
      Ni(H(2)O)(6)(2+) ion in SDS is more than two orders of magnitude higher than in
      water. The agreement between the equilibrium constants derived from kinetics and
      those obtained by static measurements confirms the validity of the proposed
      mechanism.

PMID- 22584534
TI  - Systematic review and meta-analysis of the correlates of cancer-related fatigue.

PMID- 22584535
TI  - An unusual cause of fat embolism syndrome.

PMID- 22584536
TI  - Effect of nitrous oxide exposure during surgery on the homocysteine
      concentrations of children.
AB  - BACKGROUND: Nitrous oxide converts vitamin B12 to its nonmetabolically active
      form, inhibits methionine synthase, and results in an elevation of plasma total
      homocysteine (tHcy). The authors investigated the effect of nitrous oxide
      anesthesia on the plasma tHcy concentrations in children the morning after
      surgery and whether blood concentrations of folate and vitamins B12 and B6 were
      associated with any potential increase. METHODS: The authors measured plasma tHcy
      concentrations in 32 children before and 24 h after initial exposure to nitrous
      oxide (>= 2 h). Genotype for methylenetetrahydrofolate reductase C677T and blood
      concentrations of folate, vitamins B12 and B6, and methylmalonic acid were
      measured before surgery. RESULTS: The median age of participants was 11 months (3
      126 months). The median (first, third quartile) postoperative plasma tHcy
      concentration was significantly higher than the preoperative concentration (6.4
      [4.7, 8.9] vs. 5.1[4.1, 6.4] MUM, P < 0.0001), a 25% (2%, 42%) relative increase.
      Six of 28 (21%) children with normal, age-appropriate, preexposure plasma tHcy
      concentrations had postoperative plasma tHcy concentrations greater than the
      cutoff values. The duration of nitrous oxide exposure was associated positively
      with the rise in plasma tHcy concentration (R2 = 0.696, P = < 0.001). CONCLUSION:
      Exposure to >= 2 h nitrous oxide is associated with a small, albeit statistically
      significant, increase in postoperative plasma tHcy concentrations the morning
      after surgery in young children. The clinical significance of this increase is
      unknown.

PMID- 22584537
TI  - A public-private strategy to advance the use of clinical registries.

PMID- 22584538
TI  - National performance data registries: preparing for the perfect storm.

PMID- 22584539
TI  - The Surgical Quality Alliance.

PMID- 22584540
TI  - Three distinct cases of copper deficiency in hospitalized pediatric patients.
AB  - Although copper deficiency is a rare occurrence in the developed world, attention
      should be given to the proper supplementation of minerals to at-risk pediatric
      patients. This study presents 3 distinct cases of copper deficiency in
      hospitalized patients aged 14 months, 6 years, and 12 years. Two patients had
      short bowel syndrome, requiring prolonged parenteral nutrition or complex
      intravenous fluid supplementation. The third patient was severely malnourished.
      Copper deficiency manifested in all of our patients as either microcytic anemia
      or pancytopenia with myelodysplastic syndrome. Copper deficiency is an important
      diagnosis to be considered in patients with prematurity, parenteral nutrition
      dependency, malabsorption, and/or those with malnutrition. More studies are
      needed to establish appropriate amounts of copper supplementation to replenish
      copper stores in deficient patients.

PMID- 22584541
TI  - Why do children with ADHD discontinue their medication?
AB  - OBJECTIVE: To examine factors associated with parent-reported discontinuation of
      attention-deficit/hyperactivity disorder (ADHD) medication. METHODS: The authors
      conducted a telephone survey of parents of children 6 to 18 years old who had
      recently initiated ADHD medication according to insurance claims. RESULTS: A
      total of 127 parents of children with ADHD who had recently initiated ADHD
      medication completed the survey (43% response rate); 21% discontinued the ADHD
      medication. Parents of discontinuers were less likely to report having discussed
      the risks and benefits of ADHD medication with primary care providers (59% vs
      82%, P = .03) and were more likely to report psychological side effects (58% vs
      21%, P > .001). Multivariate analyses demonstrated that both psychological side
      effects and perceived inadequate medication effectiveness were associated with
      discontinuation. CONCLUSIONS: Many children discontinue ADHD medication within
      the first year, often because of psychological side effects or perceived
      inadequate medication effectiveness. Improved methods for psychological side
      effect management, setting realistic medication goals, and assessing therapeutic
      success are needed.

PMID- 22584543
TI  - The revised Atlanta classification for acute pancreatitis: updates in imaging
      terminology and guidelines.
AB  - Imaging of acute pancreatitis requires not only an understanding of the disease
      subtypes and the myriad of associated complications but also familiarity with the
      appropriate radiologic nomenclature as defined by the Atlanta symposium in 1992
      and, more recently, by the Acute Pancreatitis Classification Working Group in
      2008. The accurate description of the radiological findings plays a critical role
      in the evaluation and management of patients with acute pancreatitis,
      particularly those with severe disease. There have been increasing efforts to
      develop uniformity in the use of terminology used to define the radiologic
      findings in acute pancreatitis, in particular, the terminology for fluid
      collections, a common area of inconsistency and confusion. Terms such as "acute
      peripancreatic fluid collections," "acute post- necrotic fluid collections,"
      "pseudocyst," and "walled-off pancreatic necrosis" are now recommended as they
      describe the evolution of fluid collections in patients with both interstitial
      and necrotizing pancreatitis and nonspecific terms such as "pancreatic abscess"
      and "phlegmon" are being abandoned. In this review we illustrate, with case
      examples, the standardized terminology used in the radiological and clinical
      description of acute pancreatitis, its severity, and complications with an
      emphasis on the role of ultrasound, computed tomography and magnetic resonance
      imaging. Different management options of the associated complications are also
      discussed. The use of standardized terminology will hopefully improve the
      communication between radiologists, gastroenterologists, and surgeons to
      facilitate treatment planning and will lead to enhanced outcomes for patients
      with acute pancreatitis as well as create uniformity for enrollment into research
      studies.

PMID- 22584542
TI  - Ophthalmic features of optic disc drusen.
AB  - PURPOSE: To evaluate the ophthalmoscopic manifestations of patients with visible
      and hidden optic disc drusen (ODD). METHOD: We studied 55 patients (100 eyes)
      with ODD that were confirmed using B-scan ultrasonography and a control group of
      60 patients (100 eyes) for differential diagnosis. We analysed the optic nerve
      features with stereoscopic photography and compared the characteristics between
      visible and hidden ODD and between hidden ODD and papilloedema. RESULTS: The
      patients with ODD presented the following ophthalmoscopic features: visible
      drusen (52%), blurred edges (84%), raised optic disc (74%), absence of optic disc
      cupping (69%), absence of venous pulse (54%), abnormal vascular branching (81%),
      presence of cilioretinal vessels (42%), peripapillary atrophy (56%) and
      haemorrhages (2%). Comparison of the qualitative characteristics of the papillae
      of the eyes with visible and hidden ODD showed statistically significant
      differences in all parameters studied, except for morphological alterations (p =
      0.851) and haemorrhage (p = 0.954). Comparison of hidden ODD with papilloedema
      showed statistically significant differences in blurred edges, disc elevation,
      absence of optic disc cupping, altered colour, anomalous vascular branching and
      optic disc haemorrhages (p < 0.005). CONCLUSIONS: Ophthalmologic features
      associated with ODD can help us to diagnose their presence and avoid confusing
      them with papilloedema.

PMID- 22584544
TI  - A phase I pharmacokinetic and bioavailability study of a sublingual fentanyl
      wafer in healthy volunteers.
AB  - BACKGROUND: The sublingual administration of opioids is a simple and noninvasive
      method that provides rapid analgesia. In this phase I study we investigated the
      pharmacokinetics and bioavailability of a fentanyl wafer in healthy volunteers.
      The principal study objective was to investigate the pharmacokinetic profile of a
      new sublingual fentanyl wafer and to establish its absolute bioavailability.
      METHODS: Twenty-four healthy volunteers, mean age 23 years, were randomly
      assigned to receive the equivalent of fentanyl 100 MUg by both the sublingual and
      IV routes. Blood samples were collected in sterile polypropylene tubes for 24
      hours after each fentanyl administration. The pharmacokinetic parameters were
      determined by model-independent pharmacokinetic analyses of the plasma fentanyl
      concentration-time profiles. RESULTS: The mean absolute bioavailability of the
      sublingual fentanyl wafer was 78.9% (90% confidence interval [CI] 51.1% to
      121.7%). The first detectable plasma fentanyl concentration time ranged from 2 to
      10 minutes in all volunteers, and the mean (+/-SD) time to peak plasma
      concentration at 0.91 (+/-0.73) hours after administration. CONCLUSION:
      Sublingual administration of fentanyl as a wafer product resulted in rapidly
      detectable plasma fentanyl concentrations. The absolute bioavailability of 78.9%
      indicated a high systemic availability of fentanyl and suggests that further
      development of this wafer is justified.

PMID- 22584545
TI  - The mu opioid receptor modulates neurotransmission in the rat spinal ventral
      horn.
AB  - BACKGROUND: Opioids inhibit excitatory neurotransmission and produce
      antinociception through MU opioid receptors (MORs). Although MORs are expressed
      in the spinal ventral horn, their functions and effects are largely unknown.
      Therefore, we examined the neuromodulatory effects of MU opioids in spinal lamina
      IX neurons at the cellular level. METHODS: The effects of the selective MU
      agonist [D-Ala(2),-N-Me-Phe(4), Gly(5)-ol]enkephalin (DAMGO) on synaptic
      transmission were examined in spinal lamina IX neurons of neonatal rats using the
      whole-cell patch-clamp technique. RESULTS: DAMGO produced outward currents in 56%
      of the lamina IX neurons recorded, with a 50% effective concentration of 0.1 MUM.
      Analysis of the current-voltage relationship revealed a reversal potential of
      approximately -86 mV. These currents were not blocked by tetrodotoxin but were
      inhibited by Ba(2+) or a selective MU antagonist. Moreover, the currents were
      suppressed by the addition of Cs(+) and tetraethylammonium or guanosine 5'-[beta
      thio]diphosphate trilithium salt to the pipette solution. In addition, DAMGO
      decreased the frequency of spontaneous excitatory and inhibitory postsynaptic
      currents, and these effects were unaltered by treatment with tetrodotoxin.
      CONCLUSION: Our results suggest that DAMGO hyperpolarizes spinal lamina IX
      neurons by G protein-mediated activation of K(+) channels after activation of
      MORs. Furthermore, activation of MORs on presynaptic terminals reduces both
      excitatory and inhibitory transmitter release. Although traditionally opioids are
      not thought to affect motor function, the present study documents neuromodulatory
      effects of MU opioids in spinal lamina IX neurons, suggesting that MORs can
      influence motor activity.

PMID- 22584546
TI  - Systemic inflammatory response does not correlate with acute lung injury
      associated with mechanical ventilation strategies in normal lungs.
AB  - BACKGROUND: Mechanical ventilation (MV) can lead to ventilator-induced lung
      injury secondary to trauma and associated increases in pulmonary inflammatory
      cytokines. There is controversy regarding the associated systemic inflammatory
      response. In this report, we demonstrate the effects of MV on systemic
      inflammation. METHODS: This report is part of a previously published study (Hong
      et al. Anesth Analg 2010;110:1652-60). Female pigs were randomized into 3 groups.
      Group H-Vt/3 was ventilated with a tidal volume (Vt) of 15 mL/kg predicted body
      weight (PBW)/positive end-expiratory pressure (PEEP) of 3 cm H(2)O; group L-Vt/3
      with a Vt of 6 mL/kg PBW/PEEP of 3 cm H2O; and group L-Vt/10 with a Vt of 6 mL/kg
      PBW/PEEP of 10 cm H(2)O, for 8 hours. Each group had 6 subjects (n = 6). Prelung
      and postlung sera were analyzed for inflammatory markers. Hemodynamics, airway
      mechanics, and arterial blood gases were monitored. RESULTS: There were no
      significant differences in systemic cytokines among groups. There were similar
      trends of serum inflammatory markers in all subjects. This is in contrast to
      findings previously published demonstrating increases in inflammatory mediators
      in bronchoalveolar lavage. CONCLUSION: Systemic inflammatory markers did not
      correlate with lung injury associated with MV.

PMID- 22584547
TI  - Therapeutic hypothermia after exsanguination.
AB  - Therapeutic hypothermia has been shown to be effective in out-of-hospital cardiac
      arrest, and use of this therapy has been expanded to involve in-hospital cardiac
      arrest. The utility of hypothermia in cardiac arrest after hemorrhage is not
      known. We describe a case of successful neurological and functional outcome after
      in-hospital pulseless electrical activity arrest secondary to exsanguination from
      an internal carotid artery rupture. Therapeutic hypothermia by surface cooling
      was initiated after acute control of the bleeding source, restoration of
      circulating blood volume, and hemodynamic stabilization. We believe therapeutic
      hypothermia use will continue to increase for in-hospital cardiac arrests.

PMID- 22584548
TI  - Prior lumbar discectomy surgery does not alter the efficacy of neuraxial labor
      analgesia.
AB  - BACKGROUND: Lumbar discectomy surgery is a common neurosurgical procedure.
      Neuraxial labor analgesia may be less effective in parturients with a history of
      discectomy surgery because of postsurgical scarring and anatomical distortion. In
      this prospective observational case-controlled study, we compared bupivacaine
      consumption per hour of labor analgesia as an indirect measure of labor analgesic
      effectiveness between women with prior discectomy surgery and those who did not
      have back surgery. METHODS: All women with prior discectomy surgery who requested
      neuraxial labor analgesia at a high-volume, single university-affiliated women's
      hospital during the study period were approached. Control subjects were matched
      for anesthesiologist skill level. The primary outcome was bupivacaine consumption
      per hour of labor analgesia. Characteristics associated with the epidural
      catheter placement including the number of interspaces attempted, time to
      placement, and number of epidural catheters replaced for inadequate analgesia
      were recorded. Subject characteristics, labor outcomes, and analgesia outcomes
      were analyzed using the Wilcoxon ranked sum or Fisher exact test. Epidural
      placement data were analyzed using the Wilcoxon signed rank, McNemar's, or sign
      test. RESULTS: Data were analyzed for 42 women in the discectomy group and 42
      women in the control group. Bupivacaine consumption per hour of labor analgesia
      was not different between groups (median [interquartile range, IQR]: discectomy
      12.7 mg/h [11.0 to 15.3] and control 13.2 mg/h [11.3 to 15.7]; difference in
      medians [95% confidence interval, CI]: -0.55 mg/h [-1.33 to 1.39]; P = 0.43). The
      interval from initiation of neuraxial analgesia and delivery and mode of delivery
      did not differ between groups. The median difference (95% CI) in the time to
      place the epidural catheter between the discectomy and control subjects was 0
      minute (-1 to 2.5); P = 0.38. More than 1 interspace was attempted in 17%
      discectomy in comparison with 2% of the control subjects-difference (95% CI) 15%
      (2-26); P = 0.03. The neuraxial technique and estimated level of catheter
      placement did not differ. Completion of the procedure by a more senior
      anesthesiologist occurred in 3 discectomy subjects and 2 control subjects (P =
      1.0). No epidural catheters were replaced. CONCLUSIONS: There was no difference
      in hourly bupivacaine consumption in parturients with prior lumbar discectomy
      surgery undergoing neuraxial labor analgesia in comparison with controls. Time to
      placement of the epidural catheter was not different either, but more interspaces
      were attempted in the discectomy group. Our findings suggest that standard
      clinical neuraxial analgesic methods are effective in women with discectomy
      surgery.

PMID- 22584549
TI  - Peripartum management of dual antiplatelet therapy and neuraxial labor analgesia
      after bare metal stent insertion for acute myocardial infarction.
AB  - A 31-year-old woman at 32 weeks' gestation presented with an ST segment elevation
      myocardial infarction with subsequent bare metal stent placement. A
      multidisciplinary team coordinated the delivery plan, including anticoagulation
      and delivery mode. Because the patient was at high risk for stent thrombosis,
      clopidogrel was discontinued after 4 weeks and bridged with eptifibatide for 7
      days. Eptifibatide was stopped for induction of labor. Twelve hours after
      eptifibatide was discontinued, hemostatic function was assessed with
      thromboelastography before initiating neuraxial analgesia. A successful operative
      vaginal delivery was performed, followed by an uncomplicated recovery.
      Clopidogrel was resumed 24 hours postpartum.

PMID- 22584550
TI  - Special article: mandragora: anesthetic of the ancients.
AB  - Initial attempts at surgical anesthesia began many centuries ago, with the plants
      of antiquity. The mandragora, or mandrake, was used as a sedative and to induce
      pain relief for surgical procedures. It has been depicted in tablets and friezes
      since the 16th century before the common era (BCE) and used for its sedative
      effects by Hannibal (second century BCE) against his enemies. The Romans used the
      mandrake for surgery. The Arabs translated the scientific work of the Ancients
      and expanded on their knowledge. They developed the Spongia Somnifera, which
      contained the juice of the mandrake plant. After the fall of the Islamic cities
      of Europe to the Christians, scientific work was translated into Latin and the
      Spongia Somnifera was used in Europe until the discovery of the use of ether for
      surgical anesthesia.

PMID- 22584551
TI  - Effect of dexmedetomidine on brain edema and neurological outcomes in surgical
      brain injury in rats.
AB  - BACKGROUND: Surgical brain injury (SBI) is damage to functional brain tissue
      resulting from neurosurgical manipulations such as sharp dissection,
      electrocautery, retraction, and direct applied pressure. Brain edema is the major
      contributor to morbidity with inflammation, necrosis, oxidative stress, and
      apoptosis likely playing smaller roles. Effective therapies for SBI may improve
      neurological outcomes and postoperative morbidities associated with brain
      surgery. Previous studies show an adrenergic correlation to blood-brain barrier
      control. The alpha-2 receptor agonist dexmedetomidine (DEX) has been shown to
      improve neurological outcomes in stroke models. We hypothesized that DEX may
      reduce brain edema and improve neurological outcomes in a rat model of SBI.
      METHODS: Male Sprague-Dawley rats (n = 63) weighing 280 to 350 g were randomly
      assigned to 1 of 4 IP treatment groups: sham IP, vehicle IP, DEX 10 mg/kg, and
      DEX 30 mg/kg. Treatments were given 30 min before SBI. These treatment groups
      were repeated to observe the physiologic impact of DEX on mean arterial blood
      pressure (MAP), heart rate (HR), and blood glucose on SBI naive animals. Rats
      were also assigned to 4 postinjury IV treatment groups: sham IV, vehicle IV, DEX
      10/5, and DEX 30/15 (DEX group doses were 10 and 30 mg/kg/hr, with 5 and 15 mg/kg
      initial loading doses, respectively). Initial loading doses began 20 min after
      SBI, followed by 2 h of infusion. SBI animals were subjected to neurological
      testing 24 h after brain injury by a blinded observer, promptly killed, and brain
      water content measured via the dry/wet weight method. RESULTS: All treatment
      groups showed a significant difference in ipsilateral frontal brain water content
      and neurological scores when compared with sham animals. However, there was no
      difference between DEX-treated and vehicle animals. Physiologic monitoring showed
      treatment with low or high doses of DEX significantly decreased MAP and HR, and
      briefly increased blood glucose compared with naive or vehicle-treated animals.
      CONCLUSIONS: DEX administration did not reduce brain edema or improve
      neurological function after SBI in this study. The statistical difference in
      brain water content and neurological scores when comparing sham treatment to
      vehicle and DEX treatments shows consistent reproduction of this model.
      Significant changes in MAP, HR, and blood glucose after DEX as compared to
      vehicle and sham treatments suggest appropriate delivery of drug.

PMID- 22584552
TI  - The effects of MDCO-2010, a serine protease inhibitor, on activated clotting time
      in blood obtained from volunteers and cardiac surgical patients.
AB  - BACKGROUND: The activated clotting time (ACT) is widely used for monitoring
      heparin anticoagulation during cardiac surgery. Celite-based ACT values are
      prolonged when aprotinin is administered. MDCO-2010, a novel serine protease
      inhibitor, is currently being evaluated as a possible alternative to aprotinin.
      Therefore, we evaluated the in vitro effects of this novel agent on ACT values
      using 3 different point-of-care instruments with kaolin or celite as an
      activator. METHODS: The study was performed in 2 parts. In the first part, blood
      samples were obtained from 15 healthy volunteers. Samples were pipetted into
      small Eppendorf tubes and 2 concentrations of the MDCO-2010 (100 and 500 nM,
      final concentration) alone or with heparin (1.2 or 2.4 U/mL) were added. ACTs
      were measured using Helena (celite), Hemochron (kaolin), and Medtronic (kaolin)
      devices. In the second part of the study, blood samples were obtained
      intraoperatively, at 5 time points, from 15 patients undergoing cardiopulmonary
      bypass. MDCO-2010 at a final concentration of 100 or 500 nM was added and ACT
      testing was performed as before. Additional coagulation tests included
      prothrombin time, activated partial thromboplastin time, fibrinogen,
      antithrombin, prothrombin, and anti-Xa levels. RESULTS: Addition of MDCO-2010
      concentration-dependently prolonged ACTs in volunteers' and patients' blood
      samples regardless of the ACT activator or device used. In volunteer samples (no
      heparin) and in patient samples (baseline and intensive care unit) percent
      changes in ACTs due to MDCO-2010 were on average 3.1 +/- 1.8 times higher (95%
      confidence interval 2.6-3.6; P < 0.001) for the celite-based Helena device
      compared with either Hemochron or Medtronic devices. CONCLUSION: MDCO-2010 causes
      less ACT prolongation with kaolin than with celite activation.

PMID- 22584553
TI  - The impact of nitrous oxide on electroencephalographic bicoherence during
      isoflurane anesthesia.
AB  - BACKGROUND: We previously reported that electroencephalographic (EEG)
      bicoherence, the degree of phase coupling among the frequency components of a
      signal, showed 2 peaks during isoflurane anesthesia. Hayashi et al. (Br J Anaesth
      2007;99:389-95) also revealed that the peak frequency of bicoherence around 10 Hz
      increased when ketamine was added. Because nitrous oxide (N(2)O) and ketamine
      share several common features, they are often treated as the same category of
      anesthetic. Here, we investigated the effect of N(2)O on EEG bicoherence and
      other EEG derivatives during isoflurane anesthesia. METHODS: Twenty patients
      (aged 34-72 years, ASA physical status I and II) of either gender who underwent
      elective laparoscopic surgery were included. Raw EEG data, along with EEG-derived
      parameters, were recorded using an A-1050 Bispectral Index (BIS) monitor and our
      self-authored Bispectral Analyzer for BIS software. We compared 2 peaks of EEG
      bicoherence (pBIC-low, around 4 Hz; and pBIC-high, around 10 Hz), as well as BIS
      and spectral edge frequency 95% (SEF95). Anesthesia was induced with 3 mg . kg(
      1) thiopental and 3 MUg . kg(-1) fentanyl. After tracheal intubation, anesthesia
      was maintained with isoflurane (expired concentration at 1.0%), oxygen, and
      nitrogen. Fentanyl was added and maintained at an estimated effect-site
      concentration of >1.5 ng . mL(-1). We obtained baseline data 1 hour after
      induction of anesthesia, then 70% N(2)O was added for 30 minutes. RESULTS: Before
      N(2)O, pBIC-low and pBIC-high were 49.3% +/- 8.3% and 42.4% +/- 11.0%. Ten
      minutes after starting N(2)O, pBIC-high decreased to 14.9% +/- 5.9% (P < 0.001),
      and it was statistically significantly lower throughout the N(2)O period.
      Meanwhile, pBIC-low transiently decreased to 37.2% +/- 12.8% (P = 0.01) during
      the early phase of N(2)O administration. Before N(2)O, BIS and SEF95 were 43.2 +/
      4.9 and 13.1 +/- 2.0 Hz, respectively. Both BIS and SEF95 slightly but
      statistically significantly decreased during N(2)O administration. Fifteen
      minutes after starting N(2)O, BIS and SEF95 were 35.7 +/- 6.2 (P < 0.001) and 8.6
      +/- 1.8 Hz (P < 0.001) and they decreased more when large delta waves emerged.
      Fifteen minutes after stopping N(2)O, BIS, SEF95, as well as pBIC-low and pBIC
      high returned to pre-N(2)O values. CONCLUSION: Dissimilar to the effect of
      ketamine, N(2)O significantly decreases pBIC-high during isoflurane anesthesia.

PMID- 22584554
TI  - Intravenous sodium bicarbonate verifies intravenous position of catheters in
      ventilated children.
AB  - BACKGROUND: Vascular access in children carries a significant risk of accidental
      extravasation of IV fluids and medications with the potential for tissue injury.
      In this prospective controlled study we assessed the diagnostic utility of using
      IV diluted sodium bicarbonate to confirm placement of IV catheters in ventilated
      children. Diluted sodium bicarbonate was created using undiluted standard 8.4% (1
      mEq/mL) sodium bicarbonate mixed in a 1:3 and 1:5 ratio with sterile water to
      achieve a final diluted concentration of 2.1% (0. 25 mEq/mL) and 1.05% (0.125
      mEq/mL) sodium bicarbonate, respectively. METHODS: In 18 ASA I-II mechanically
      ventilated children ages 1 to 8 years, the effects of 1 mL/kg of dilute 2.1%,
      1.05% sodium bicarbonate, or 0.9% normal saline, injected in a randomized order,
      were analyzed. All children had oxygen saturation, arterial blood pressure,
      electrocardiograph, and end-tidal carbon dioxide (ETCO(2)) monitoring. In
      addition, venous blood samples were taken before injection and 10 minutes after
      the final injection for analysis of venous blood pH and electrolytes. RESULTS: In
      children, IV diluted 2.1% sodium bicarbonate resulted in significantly increased
      etco(2) (mean of 32.8 +/- 3.4 mm Hg to 39.0 +/- 3.5 mm Hg, P < 0.001), a mean
      increase of 6.2 mm Hg (95% prediction interval: 4.3 to 8.1 mm Hg) within 3
      breaths. Intravenous diluted 1.05% sodium bicarbonate caused a less pronounced
      but still significant increase in etco(2) (33.4 +/- 3.8 mm Hg to 36.3 +/- 3.4 mm
      Hg, P < 0.001), a mean increase of 2.9 mm Hg (95% prediction interval: 1.8 to 4.1
      mm Hg) within 3 breaths. Normal saline did not result in any significant changes,
      with a mean increase of 0.06 mm Hg (95% prediction interval: -1.3 to 1.4 mm Hg).
      Both concentrations of sodium bicarbonate were easily differentiated from normal
      saline injection by blinded anesthesiologists observing the change in etco(2)
      values immediately after injection. Analysis of pre- and postinjection venous pH,
      bicarbonate, and sodium levels could not detect clinically significant changes. A
      small but statistically significant increase in venous bicarbonate was noted.
      CONCLUSION: The injection of 2.1% sodium bicarbonate in mechanically ventilated
      ASA I-II children identified intravascular placement and patency of an IV
      catheter by an increase in the exhaled CO(2) concentration. The injections did
      not have any clinically significant effects on blood pH, bicarbonate, or sodium
      concentration.

PMID- 22584555
TI  - Special article: impact versus impact factor: revisiting a classic article that
      was never cited. 1923.

PMID- 22584556
TI  - Inside anesthesia breathing circuits: time to reach a set sevoflurane
      concentration in toddlers and newborns: simulation using a test lung.
AB  - We measured the time it takes to reach the desired inspired anesthetic
      concentration using the Primus (Dragerwerk, AG, Lubeck, Germany) and the Avance
      (GE Datex-Ohmeda, Munich, Germany) anesthesia machines with toddler and newborn
      ventilation settings. The time to reach 95% of inspired target sevoflurane
      concentration was measured during wash-in from 0 to 6 vol% sevoflurane and during
      wash-out from 6 to 0 vol% with fresh gas flows equal to 1 and 2 times the minute
      ventilation. The Avance was faster than the Primus (65 seconds [95% confidence
      interval (CI): 55 to 78] vs 310 seconds [95% CI: 261 to 359]) at 1.5 L/min fresh
      gas flow, tidal volume of 50 mL, and 30 breaths/min. Times were shorter by the
      same magnitude at higher fresh gas flows and higher minute ventilation rates. The
      effect of doubling fresh gas flow was variable and less than expected. The Primus
      is slower during newborn than toddler ventilation, whereas the Avance's response
      time was the same for newborn and toddler ventilation. Our data confirm that the
      time to reach the target-inspired anesthetic concentration depends on breathing
      circuit volume, fresh gas flow, and minute ventilation.

PMID- 22584557
TI  - Time delay of monitors of the hypnotic component of anesthesia: analysis of state
      entropy and index of consciousness.
AB  - Monitors evaluating the hypnotic component of anesthesia by analyzing the
      electroencephalogram (EEG) may help to decrease the incidence of intraoperative
      awareness with recall. To calculate an index representing the anesthetic level,
      these monitors have different time delays until the correct index is displayed.
      In previous studies, intraoperatively recorded real and simulated EEG signals
      were used to determine time delays of cerebral state and Narcotrend and
      Bispectral indices. In the present study, we determined time delays of state
      entropy and index of consciousness. For this purpose, recorded real and simulated
      EEG sequences representing different anesthetic levels were played back to the
      tested monitors. Simulated and real perioperatively recorded EEG signals
      indicating stable states "awake," "general anesthesia," and "cortical
      suppression" were used to evaluate the time delays. Time delays were measured
      when switching from one state to another and were defined as the required time
      span of the monitor to reach the stable target index. Comparable results were
      obtained using simulated and real EEG sequences. Time delays were not constant
      and ranged from 18 to 152 seconds. They were also different for increasing and
      decreasing values. Time delays were dependent on starting and target index
      values. Time delays of index calculation may limit the investigated monitor's
      ability to prevent interoperative awareness with recall. Different time delays
      for increasing and decreasing transitions could be a problem if the monitors are
      used for pharmacodynamic studies.

PMID- 22584558
TI  - Systemic lidocaine to improve postoperative quality of recovery after ambulatory
      laparoscopic surgery.
AB  - BACKGROUND: Perioperative systemic lidocaine has been shown to have beneficial
      postoperative analgesic effects. The only previous study examining the use of
      lidocaine in the outpatient setting did not detect an opioid-sparing effect after
      hospital discharge. More importantly, it is unknown whether systemic lidocaine
      provides a better postoperative quality of recovery to patients undergoing
      ambulatory surgery. Our objective in the current study was to examine the effect
      of systemic lidocaine on postoperative quality of recovery in patients undergoing
      outpatient laparoscopic surgery. METHODS: The study was a prospective,
      randomized, double-blind, placebo-controlled clinical trial. Healthy female
      subjects were randomized to receive lidocaine (1.5 mg/kg bolus followed by a 2
      mg/kg/h infusion until the end of the surgical procedure) or the same volume of
      saline. The primary outcome was the Quality of Recovery-40 questionnaire at 24
      hours after surgery. A 10-point difference represents a clinically relevant
      improvement in quality of recovery based on previously reported values on the
      mean and range of the Quality of Recovery-40 score in patients after anesthesia
      and surgery. Other data collected included opioid consumption, pain scores, and
      time to meet hospital discharge. Data were compared using group t tests and the
      Wilcoxon exact test. The association between opioid consumption and quality of
      recovery was evaluated using Spearman rho. P < 0.01 was used to reject the null
      hypothesis for the primary outcome. RESULTS: Seventy subjects were recruited and
      63 completed the study. There were no baseline differences regarding subject and
      surgical characteristics between the study groups. Patients in the lidocaine
      group had better global quality of recovery scores compared with the saline
      group, median difference of 16 (99% confidence interval [CI], 2-28), P = 0.002.
      Patients in the lidocaine group met hospital discharge criteria faster than the
      saline group, mean difference of -26 minutes (95% CI, -6 to -46 minutes) (P =
      0.03). After hospital discharge, subjects in the lidocaine group required less
      oral opioids, median difference of -10 (95% CI, 0 to -30) (oral milligrams
      morphine equivalents), than the saline group (P = 0.01). There was an inverse
      association between postoperative opioid consumption and quality of recovery (rho
      = 0.64, P < 0.001). CONCLUSIONS: Systemic lidocaine improves postoperative
      quality of recovery in patients undergoing outpatient laparoscopy. Patients who
      received lidocaine had less opioid consumption, which translated to a better
      quality of recovery. Lidocaine is a safe, inexpensive, effective strategy to
      improve quality of recovery after ambulatory surgery.

PMID- 22584559
TI  - The systemic and regional hemodynamic effects of phenylephrine in sheep under
      normal conditions and during early hyperdynamic sepsis.
AB  - BACKGROUND: Phenylephrine treatment of hypotension in sepsis raises concern
      because it may decrease vital organ bloodflow. Accordingly, we investigated the
      effects of phenylephrine on systemic and regional bloodflow in normal and septic
      sheep. METHODS: Responses to phenylephrine or vehicle infusion for 6 hours were
      determined in conscious normal sheep and sheep with early sepsis induced by
      administration of live Escherichia coli. Cardiac output and coronary, mesenteric,
      and renal bloodflow were measured with implanted flow probes. RESULTS: In normal
      sheep, phenylephrine decreased cardiac output and heart rate (HR) but increased
      stroke volume and mean arterial blood pressure (MAP) (84 +/- 6 to 108 +/- 6 mm
      Hg, magnitude of mean difference [diff.] 19 [22.6%]; 95% confidence intervals
      [CI], 17-21). There were significant decreases in regional conductance values
      with a transient decrease in mesenteric bloodflow, no change in coronary
      bloodflow, and increased renal bloodflow (222 +/- 53 to 271 +/- 55 mL/min; diff.
      31 [13.9%]; 95% CI, 26-36). During hyperdynamic sepsis, vasodilatation and
      increased bloodflow occurred in all vascular beds. Phenylephrine restored MAP and
      stroke volume to baseline values, but HR, cardiac output, and total peripheral
      conductance progressively decreased. Phenylephrine decreased mesenteric and
      coronary conductance, with no sustained reduction in flows, but renal conductance
      was significantly decreased and overall renal bloodflow increased (293 +/- 22 vs
      347 +/- 100 mL/min; diff. 55 [18.8%]; 95% CI, 47-65). CONCLUSIONS: In sheep with
      early hyperdynamic sepsis, phenylephrine, at a dose that restored MAP, increased
      stroke volume and renal bloodflow while decreasing HR and coronary bloodflow but
      not mesenteric bloodflow. Similar responses were seen in normal animals.

PMID- 22584560
TI  - Receptor specificity defines algogenic properties of propofol and fospropofol.
AB  - BACKGROUND: Propofol-evoked injection site pain is not observed with fospropofol.
      We hypothesized that unlike propofol, fospropofol does not activate the irritant
      receptor, transient receptor potential 1 (TRPA1). METHODS: We tested the
      hypothesis using electrophysiology and behavioral studies. RESULTS: Our data
      demonstrate that propofol (100 MUM) evokes an inward current only in TRPA1
      expressing neurons. However, fospropofol (100 MUM and 1 mM) is unable to evoke
      depolarizing currents in either TRPA1-positive or TRPA1-negative neurons. Both
      propofol and fospropofol produced general anesthesia. CONCLUSIONS: The lack of
      algogenic activity in fospropofol is most likely the result of its inability to
      activate TRPA1 on nociceptors.

PMID- 22584561
TI  - [Endogenous hyperinsulinism: review and follow-up of 24 cases].
AB  - Hypoglycemia due to endogenous hyperinsulinism (EH) is diagnosed in a symptomatic
      patient with low levels of plasma glucose concomitant with elevated plasma
      insulin and C-peptide. Causes of EH are pancreatic islet-cells disease, use of
      insulin secretagogues, and autoimmune hypoglycemia. In this review, the authors
      studied 24 patients with hypoglycemia due to endogenous hyperinsulinism in order
      to describe aspects of diagnosis and treatment. Our study demonstrated that after
      12 hours of fasting (mini-fasting test; at least three samples), all patients
      presented the diagnostic criteria for EH. Additionally, we found that 11 of 12
      patients (91.7%) who underwent glucagon test achieved glucose levels less than 50
      mg/dL and below baseline after 120 minutes. Mini-fasting (3 samples) and glucagon
      test may be useful to prevent prolonged fasting test to clarify the diagnosis of
      endogenous hyperinsulinism.

PMID- 22584562
TI  - Reproductive physiology, and physical and sexual development of female offspring
      born to diabetic dams.
AB  - OBJECTIVES: The objective of this study was to evaluate physical and sexual
      development and reproductive physiology in female rat offspring that developed in
      hyperglycemia conditions in utero and during lactation. MATERIALS AND METHODS:
      Maternal diabetes was induced in female rats by a single IV injection of
      streptozotocin before mating. Female offspring development was evaluated by means
      of the following parameters: physical development; age of vaginal opening and
      first estrus; weight and histological evaluation of uterus and ovaries; duration
      of the estrous cycle, sexual behavior, and fertility after natural mating.
      RESULTS: In the female offspring, maternal diabetes caused delays in initial
      physical development; diminution in ovary weight and number of follicles; and
      inferior reproductive performance compared with the control group. CONCLUSIONS:
      The exposure to hyperglycemia in uterus and during lactation caused delays in
      physical and sexual development, and affected the reproductive physiology of
      female rats negatively.

PMID- 22584563
TI  - [Metabolic syndrome in adolescents of different nutritional status].
AB  - OBJECTIVE: To investigate the prevalence of metabolic syndrome (MetS) in
      adolescents of different nutritional status. SUBJECTS AND METHODS: The sample
      consisted of 582 adolescents aged 12 to 18 years. Body mass index (BMI)
      classification of nutritional status was performed using the NCHS growth charts.
      MetS diagnosis was determined by the presence of three or more risk factors.
      RESULTS: Overall MetS prevalence was 6.7% (CI: 4.9%-9%); in boys, prevalence was
      9.4%; and in girls, 4.1%. MetS prevalence was 17.2% (CI: 10%-28.2%) and 37.1%
      (CI: 23.2%-53.7%) in overweight and obese adolescents, respectively. All obese
      adolescents had at least one risk factor present, and demonstrated high MetS
      prevalence ratio compared with adolescents of normal weight (PR: 11.1; CI: 5.75
      21.47). CONCLUSION: High prevalence of MetS was observed in obese adolescents.
      Prevention strategies should focus on body weight control since the beginning of
      adolescence.

PMID- 22584564
TI  - [Importance of nutritional counseling and dietary fiber content on glycemic
      control in type 2 diabetic patients under intensive educational intervention].
AB  - OBJECTIVE: To evaluate the importance of nutritional counseling within a set of
      multidisciplinary interventions. SUBJECTS AND METHODS: Forty-seven patients with
      type 2 diabetes and hyperglycemia (A1C >= 8%), treated conventionally (n = 19,
      GC) or intensively in six weekly visits (n = 28, GI) were analyzed. We evaluated
      mean weekly blood glucose (MWG) at baseline and after 6 weeks in both groups.
      RESULTS: GI reduced caloric (p = 0.001), carbohydrate (p = 0.004), and fat (p =
      0.001) intake, and increased fiber consumption, while GC reduced fiber intake (p
      = 0.018). Glycemic control (MWG <= 150 mg/dL) occurred in 75% of GI patients and
      in 31.6% of CG patients (p = 0.003), with negative correlation between changes in
      fiber intake and MWG values (r =-0.309; P = 0.035). Results were maintained after
      12 weeks. CONCLUSION: Educational short-term intensive intervention was more
      effective than conventional treatment to achieve glycemic control. Our results
      also indicate that a more appropriate fiber content in the diet contributes for
      better blood glucose control in these patients.

PMID- 22584565
TI  - Prescription patterns for diabetes mellitus and therapeutic implications: a
      population-based analysis.
AB  - OBJECTIVE: To analyze drug prescriptions for insulin and oral antidiabetic drugs
      in type 1 and type 2 diabetes mellitus patients seen in the Brazilian Public
      Healthcare System (Unified Health System - SUS) in Ribeirao Preto, SP, Brazil.
      SUBJECTS AND METHODS: All the patients with diabetes seen in the SUS in the
      western district of Ribeirao Preto, SP, Brazil between March/2006 and
      February/2007 were included in the study. RESULTS: A total of 3,982 patients were
      identified. Mean age of the patients was 60.6 years, and 61.0% were females.
      Sixty percent of the patients were treated with monotherapy. Doses of oral
      antidiabetic drugs were lower in monotherapy than in polytherapy. Ten patients
      received doses of glibenclamide or metformin above the recommended maximum doses,
      and in elderly patients there was no reduction in drug doses. CONCLUSION:
      Monotherapy with oral antidiabetic drugs was the predominant procedure, and the
      doses were not individualized according to age.

PMID- 22584566
TI  - Effects of subclinical hypothyroidism treatment on psychiatric symptoms, muscular
      complaints, and quality of life.
AB  - OBJECTIVES: To evaluate the impact of subclinical hypothyroidism (sHT) treatment
      on health-related quality of life (QoL), psychiatric symptoms, clinical score,
      and muscle function. MATERIALS AND METHODS: In this randomized double-blind
      study, patients were assigned either to treatment (n = 35) or placebo (n = 36).
      Clinical and psychiatric symptoms were assessed by the Zulewski, Hamilton and
      Beck scales. QoL was assessed by the SF-36 questionnaire. Assessments of
      quadriceps (QS) and inspiratory muscle (IS) strength were performed by a chair
      dynamometer and a manuvacuometer. RESULTS: Treatment improved IS (+11.5 +/- 17.2;
      p = 0.041), as did QoL domains "Pain" and "Role Physical" (+19.7 +/- 15.2, 0.039
      and +22.1 +/- 47.5, p = 0.054; respectively). Clinical and psychiatric symptoms
      showed similar responses to both interventions. CONCLUSIONS: sHT treatment
      improved IS and physical aspects of QoL, despite no impact in other muscle
      parameters. Clinical score, psychiatric symptoms, and SF-36 domains, based on
      mental dimensions of QoL may be more susceptible to "placebo effect" in patients
      with sHT.

PMID- 22584567
TI  - Prevalence of obesity and cardiovascular risk in patients with HIV/AIDS in Porto
      Alegre, Brazil.
AB  - OBJECTIVE: The aim of this study was to discover the prevalence of overweight,
      obesity and cardiovascular risk in our HIV/AIDS outpatients according to sex,
      antiretroviral therapy and other variables. SUBJECTS AND METHODS: Patients
      underwent an anthropometric assessment. Body mass index and waist circumference
      were used to classify their nutritional status and their cardiovascular risk.
      RESULTS: The majority of the 345 patients (58.8%) were males. Obesity was
      detected in 8.3% of them; 34.2% were overweight, and 5.2% malnourished. Near half
      of them (51.3%) had some cardiovascular risk, with increased risk in 24.6% of
      them, and substantially increased risk in 26.7% of them. CONCLUSIONS: Overweight
      and obesity were highly prevalent. Women were more frequently obese (OR = 3.53;
      IC 95%, 1.47 < OR < 8.69), and their cardiovascular risk was often higher (OR =
      6.97; IC 95%, 4.16 < OR < 11.76). The prevalence of obesity and cardiovascular
      risk did not change according to antiretroviral therapy or other variables.

PMID- 22584568
TI  - [Overweight and obesity in school children: association between biopsychological,
      socioeconomic and behavioral factors].
AB  - OBJECTIVE: To verify the association between the behavioral, biopsychological,
      and socioeconomic factors in overweight and obese students. SUBJECTS AND METHODS:
      The sample involved 393 students from state and private schools in
      Florianopolis/SC, mean age of 9.9 +/- 1.7, with 41% male subjects. A
      questionnaire adapted from Oliveira e cols. was applied in the interview;
      anthropometric information (body mass and height) was used to calculate the BMI,
      and individuals were classified in overweight and obese according to Conde and
      Monteiro. RESULTS: As for the distribution of obesity and overweight by gender,
      girls showed a similar degree, while among boys, overweight individuals
      represented 77% of the sample. There were associations between female gender,
      economic status, ethnicity, school, and type of food with p ranging from < 0.001
      to 0.003. CONCLUSION: It was found that the behavioral, biopsychological, and
      socioeconomic factors seem to interfere with overweight and obesity in students
      of Florianopolis.

PMID- 22584569
TI  - Does undetectable basal Tg measured with a highly sensitive assay in the absence
      of antibodies and combined with normal ultrasonography ensure the absence of
      disease in patients treated for thyroid carcinoma?
AB  - It has been proposed that, in patients treated for well-differentiated thyroid
      carcinoma, undetectable basal thyroglobulin (Tg) levels measured with a highly
      sensitive assay in the absence of anti-thyroglobulin antibodies (TgAb) and
      combined with negative neck ultrasonography (US) ensured the absence of disease.
      We report a series of five patients with well-differentiated (papillary)
      carcinoma submitted to total thyroidectomy with apparently complete tumor
      resection, followed by remnant ablation with (131)I (100-150 mCi), who had no
      distant metastases upon initial post-therapy whole-body scanning. When tumor
      recurrence or persistence was detected, these patients presented undetectable
      basal Tg (0.1 ng/mL) in the absence of TgAb, and US showed no anomalies. Two
      patients had lymph node metastases, one had mediastinal metastases, bone
      involvement was observed in one patient, and local recurrence in one. We conclude
      that further studies are needed to define in which patients undetectable basal Tg
      (negative TgAb) combined with negative US is sufficient, and no additional tests
      are required.

PMID- 22584570
TI  - Neurodegeneration-associated TDP-43 interacts with fragile X mental retardation
      protein (FMRP)/Staufen (STAU1) and regulates SIRT1 expression in neuronal cells.
AB  - Despite the identification of the 43 kDa transactive response DNA-binding protein
      (TDP-43) as a major pathological signatory protein in a wide range of
      neurodegenerative diseases, the mechanistic role of TDP-43 in neurodegenerative
      disorders is still poorly understood. Here, we report that TDP-43 is physically
      associated with fragile X mental retardation protein (FMRP) and Staufen (STAU1)
      to form a functional complex. Differential microarray analysis revealed that the
      expression of a collection of functionally important genes including Sirtuin
      (SIRT1) is regulated by this complex. RNA-immunoprecipitation (RIP) and RNA pull
      down assays demonstrated that TDP-43/FMRP/STAU1 specifically binds to the 3'-UTR
      of SIRT1 mRNA, and that knockdown the expression of any one of these three
      proteins resulted in the reduction of SIRT1 mRNA and protein. SIRT1 is implicated
      in double-stranded DNA break repair and is required for cell survival. Indeed,
      depletion of TDP-43/FMRP/STAU1 sensitizes cells to apoptosis and DNA damages.
      Collectively, our results revealed a molecular mechanism for the cellular
      function of TDP-43 and might shed new light on the understanding of the
      mechanistic role of TDP-43 in neurodegenerative diseases.

PMID- 22584571
TI  - Myocardial regulation of lipidomic flux by cardiolipin synthase: setting the beat
      for bioenergetic efficiency.
AB  - Lipidomic regulation of mitochondrial cardiolipin content and molecular species
      composition is a prominent regulator of bioenergetic efficiency. However, the
      mechanisms controlling cardiolipin metabolism during health or disease
      progression have remained elusive. Herein, we demonstrate that cardiac myocyte
      specific transgenic expression of cardiolipin synthase results in accelerated
      cardiolipin lipidomic flux that impacts multiple aspects of mitochondrial
      bioenergetics and signaling. During the postnatal period, cardiolipin synthase
      transgene expression results in marked changes in the temporal maturation of
      cardiolipin molecular species during development. In adult myocardium,
      cardiolipin synthase transgene expression leads to a marked increase in symmetric
      tetra-18:2 molecular species without a change in total cardiolipin content.
      Mechanistic analysis demonstrated that these alterations result from increased
      cardiolipin remodeling by sequential phospholipase and
      transacylase/acyltransferase activities in conjunction with a decrease in
      phosphatidylglycerol content. Moreover, cardiolipin synthase transgene expression
      results in alterations in signaling metabolites, including a marked increase in
      the cardioprotective eicosanoid 14,15-epoxyeicosatrienoic acid. Examination of
      mitochondrial bioenergetic function by high resolution respirometry demonstrated
      that cardiolipin synthase transgene expression resulted in improved mitochondrial
      bioenergetic efficiency as evidenced by enhanced electron transport chain
      coupling using multiple substrates as well as by salutary changes in Complex III
      and IV activities. Furthermore, transgenic expression of cardiolipin synthase
      attenuated maladaptive cardiolipin remodeling and bioenergetic inefficiency in
      myocardium rendered diabetic by streptozotocin treatment. Collectively, these
      results demonstrate the unanticipated role of cardiolipin synthase in maintaining
      physiologic membrane structure and function even under metabolic stress, thereby
      identifying cardiolipin synthase as a novel therapeutic target to attenuate
      mitochondrial dysfunction in diabetic myocardium.

PMID- 22584572
TI  - Protein inhibitor of activated STAT3 (PIAS3) protein promotes SUMOylation and
      nuclear sequestration of the intracellular domain of ErbB4 protein.
AB  - ErbB4 is a receptor tyrosine kinase implicated in the development and homeostasis
      of the heart, central nervous system, and mammary gland. Cleavable isoforms of
      ErbB4 release a soluble intracellular domain (ICD) that can translocate to the
      nucleus and function as a transcriptional coregulator. In search of regulatory
      mechanisms of ErbB4 ICD function, we identified PIAS3 as a novel interaction
      partner of ErbB4 ICD. In keeping with the small ubiquitin-like modifier (SUMO) E3
      ligase function of protein inhibitor of activated STAT (PIAS) proteins, we showed
      that the ErbB4 ICD is modified by SUMO, and that PIAS3 stimulates the
      SUMOylation. Upon overexpression of PIAS3, the ErbB4 ICD generated from the full
      length receptor accumulated into the nucleus in a manner that was dependent on
      the functional nuclear localization signal of ErbB4. In the nucleus, ErbB4
      colocalized with PIAS3 and SUMO-1 in promyelocytic leukemia nuclear bodies,
      nuclear domains involved in regulation of transcription. Accordingly, PIAS3
      overexpression had an effect on the transcriptional coregulatory activity of
      ErbB4, repressing its ability to coactivate transcription with Yes-associated
      protein. Finally, knockdown of PIAS3 with siRNA partially rescued the inhibitory
      effect of the ErbB4 ICD on differentiation of MDA-MB-468 breast cancer and HC11
      mammary epithelial cells. Our findings illustrate that PIAS3 is a novel regulator
      of ErbB4 receptor tyrosine kinase, controlling its nuclear sequestration and
      function.

PMID- 22584573
TI  - GQ-16, a novel peroxisome proliferator-activated receptor gamma (PPARgamma)
      ligand, promotes insulin sensitization without weight gain.
AB  - The recent discovery that peroxisome proliferator-activated receptor gamma
      (PPARgamma) targeted anti-diabetic drugs function by inhibiting Cdk5-mediated
      phosphorylation of the receptor has provided a new viewpoint to evaluate and
      perhaps develop improved insulin-sensitizing agents. Herein we report the
      development of a novel thiazolidinedione that retains similar anti-diabetic
      efficacy as rosiglitazone in mice yet does not elicit weight gain or edema,
      common side effects associated with full PPARgamma activation. Further
      characterization of this compound shows GQ-16 to be an effective inhibitor of
      Cdk5-mediated phosphorylation of PPARgamma. The structure of GQ-16 bound to
      PPARgamma demonstrates that the compound utilizes a binding mode distinct from
      other reported PPARgamma ligands, although it does share some structural features
      with other partial agonists, such as MRL-24 and PA-082, that have similarly been
      reported to dissociate insulin sensitization from weight gain. Hydrogen/deuterium
      exchange studies reveal that GQ-16 strongly stabilizes the beta-sheet region of
      the receptor, presumably explaining the compound's efficacy in inhibiting Cdk5
      mediated phosphorylation of Ser-273. Molecular dynamics simulations suggest that
      the partial agonist activity of GQ-16 results from the compound's weak ability to
      stabilize helix 12 in its active conformation. Our results suggest that the
      emerging model, whereby "ideal" PPARgamma-based therapeutics stabilize the beta
      sheet/Ser-273 region and inhibit Cdk5-mediated phosphorylation while minimally
      invoking adipogenesis and classical agonism, is indeed a valid framework to
      develop improved PPARgamma modulators that retain antidiabetic actions while
      minimizing untoward effects.

PMID- 22584574
TI  - In vivo, fatty acid translocase (CD36) critically regulates skeletal muscle fuel
      selection, exercise performance, and training-induced adaptation of fatty acid
      oxidation.
AB  - For ~40 years it has been widely accepted that (i) the exercise-induced increase
      in muscle fatty acid oxidation (FAO) is dependent on the increased delivery of
      circulating fatty acids, and (ii) exercise training-induced FAO up-regulation is
      largely attributable to muscle mitochondrial biogenesis. These long standing
      concepts were developed prior to the recent recognition that fatty acid entry
      into muscle occurs via a regulatable sarcolemmal CD36-mediated mechanism. We
      examined the role of CD36 in muscle fuel selection under basal conditions, during
      a metabolic challenge (exercise), and after exercise training. We also
      investigated whether CD36 overexpression, independent of mitochondrial changes,
      mimicked exercise training-induced FAO up-regulation. Under basal conditions CD36
      KO versus WT mice displayed reduced fatty acid transport (-21%) and oxidation (
      25%), intramuscular lipids (less than or equal to -31%), and hepatic glycogen (
      20%); but muscle glycogen, VO(2max), and mitochondrial content and enzymes did
      not differ. In acutely exercised (78% VO(2max)) CD36-KO mice, fatty acid
      transport (-41%), oxidation (-37%), and exercise duration (-44%) were reduced,
      whereas muscle and hepatic glycogen depletions were accelerated by 27-55%,
      revealing 2-fold greater carbohydrate use. Exercise training increased mtDNA and
      beta-hydroxyacyl-CoA dehydrogenase similarly in WT and CD36-KO muscles, but FAO
      was increased only in WT muscle (+90%). Comparable CD36 increases, induced by
      exercise training (+44%) or by CD36 overexpression (+41%), increased FAO
      similarly (84-90%), either when mitochondrial biogenesis and FAO enzymes were up
      regulated (exercise training) or when these were unaltered (CD36 overexpression).
      Thus, sarcolemmal CD36 has a key role in muscle fuel selection, exercise
      performance, and training-induced muscle FAO adaptation, challenging long held
      views of mechanisms involved in acute and adaptive regulation of muscle FAO.

PMID- 22584575
TI  - Scientific side trips: six excursions from the beaten path.

PMID- 22584576
TI  - The human biliverdin reductase-based peptide fragments and biliverdin regulate
      protein kinase Cdelta activity: the peptides are inhibitors or substrate for the
      protein kinase C.
AB  - PKCdelta, a Ser/Thr kinase, promotes cell growth, tumorigenesis, and apoptosis.
      Human biliverdin reductase (hBVR), a Ser/Thr/Tyr kinase, inhibits apoptosis by
      reducing biliverdin-IX to antioxidant bilirubin. The enzymes are activated by
      similar stimuli. Reportedly, hBVR is a kinase-independent activator of PKCdelta
      and is transactivated by the PKC (Gibbs, P. E., Miralem, T., Lerner-Marmarosh,
      N., Tudor, C., and Maines, M. D. (2012) J. Biol. Chem. 287, 1066-1079).
      Presently, we examined interactions between the two proteins in the context of
      regulation of their activities and defining targets of hBVR phosphorylation by
      PKCdelta. LC-MS/MS analysis of PKCdelta-activated intact hBVR identified
      phosphorylated serine positions 21, 33, 230, and 237, corresponding to the hBVR
      Src homology-2 domain motif (Ser(230) and Ser(237)), flanking the ATP-binding
      motif (Ser(21)) and in PHPS sequence (Ser(33)) as targets of PKCdelta. Ser(21)
      and Ser(230) were also phosphorylated in hBVR-based peptides. The Ser(230)
      containing peptide was a high affinity substrate for PKCdelta in vitro and in
      cells; the relative affinity was PKCdelta > PKCbetaII > PKCzeta. Two overlapping
      peptides spanning this substrate, KRNRYLSF and SFHFKSGSL, were effective
      inhibitors of PKCdelta kinase activity and PKCdelta-supported activation of
      transcription factors Elk1 and NF-kappaB. Only SFHFKSGSL, in PKCdelta-transfected
      phorbol 12-myristate 13-acetate-stimulated cells, caused membrane blebbing and
      cell loss. Biliverdin noncovalently inhibited PKCdelta, whereas PKCdelta
      potentiated hBVR reductase activity and accelerated the rate of bilirubin
      formation. This study, together with previous findings, reveals an unexpected
      regulatory interplay between PKCdelta and hBVR in modulating cell death/survival
      in response to various activating stimuli. In addition, this study has identified
      novel substrates for and inhibitors of PKCdelta. We suggest that hBVR-based
      technology may have utility to modulate PKCdelta-mediated functions in the cell.

PMID- 22584577
TI  - Highly aggregated antibody therapeutics can enhance the in vitro innate and late
      stage T-cell immune responses.
AB  - Aggregation of biotherapeutics has the potential to induce an immunogenic
      response. Here, we show that aggregated therapeutic antibodies, previously
      generated and determined to contain a variety of attributes (Joubert, M. K., Luo,
      Q., Nashed-Samuel, Y., Wypych, J., and Narhi, L. O. (2011) J. Biol. Chem. 286,
      25118-25133), can enhance the in vitro innate immune response of a population of
      naive human peripheral blood mononuclear cells. This response depended on the
      aggregate type, inherent immunogenicity of the monomer, and donor responsiveness,
      and required a high number of particles, well above that detected in marketed
      drug products, at least in this in vitro system. We propose a cytokine signature
      as a potential biomarker of the in vitro peripheral blood mononuclear cell
      response to aggregates. The cytokines include IL-1beta, IL-6, IL-10, MCP-1, MIP
      1alpha, MIP-1beta, MMP-2, and TNF-alpha. IL-6 and IL-10 might have an
      immunosuppressive effect on the long term immune response. Aggregates made by
      stirring induced the highest response compared with aggregates made by other
      methods. Particle size in the 2-10 MUm range and the retention of some folded
      structure were associated with an increased response. The mechanism of aggregate
      activation at the innate phase was found to occur through specific cell surface
      receptors (the toll-like receptors TLR-2 and TLR-4, FcgammaRs, and the complement
      system). The innate signal was shown to progress to an adaptive T-cell response
      characterized by T-cell proliferation and secretion of T-cell cytokines.
      Investigating the ability of aggregates to induce cytokine signatures as
      biomarkers of immune responses is essential for determining their risk of
      immunogenicity.

PMID- 22584578
TI  - De novo DNA methylation is required to restrict T helper lineage plasticity.
AB  - Naive CD4+ T cells are highly plastic and can differentiate into discrete
      lineages with unique functions during an immune response. Once differentiated,
      helper T cells maintain a stable transcriptional memory of their initial lineage
      choice and resist redifferentiation. During embryogenesis, de novo DNA
      methylation operates on the hypomethylated genome of the blastocyst to achieve
      tissue-specific patterns of gene expression. Similarly, the ifngamma promoter is
      hypomethylated in naive T cells, but Th2, Th17, and iTreg differentiation is
      accompanied by substantial de novo DNA methylation at this locus. To determine
      whether de novo DNA methylation is required to restrict T helper lineage
      plasticity, we used mice with T cell-specific deletion of the methyltransferase
      DNMT3a. Induction of lineage-specific cytokines occurred normally in the absence
      of DNMT3a, however, DNMT3a-deficient Th2, Th17, and iTreg completely failed to
      methylate the ifngamma promoter. This was accompanied by an increase in the
      transcriptionally permissive trimethyl H3K4 mark, and a reduction in inhibitory
      H3K27 methylation at the ifngamma locus. Failed de novo methylation resulted in
      failed silencing of the ifngamma gene, as DNMT3a-deficient Th2, Th17, and iTreg
      cells produced significant levels of IFNgamma following restimulation in the
      presence of IL-12. Therefore, DNMT3a-mediated DNA methylation restricts T helper
      plasticity by establishing an epigenetically silent chromatin structure at
      regulatory regions of the ifngamma gene.

PMID- 22584579
TI  - Differential regulation of androgen receptor by PIM-1 kinases via phosphorylation
      dependent recruitment of distinct ubiquitin E3 ligases.
AB  - Androgen receptor (AR) plays a pivotal role in prostate cancer. Regulation of AR
      transcriptional activity by post-translational modifications, such as
      phosphorylation by multiple kinases, is well documented. Here, we report that two
      PIM-1 kinase isoforms which are up-regulated during prostate cancer progression,
      namely PIM-1S and PIM-1L, modulate AR stability and transcriptional activity
      through differentially phosphorylating AR at serine 213 (Ser-213) and threonine
      850 (Thr-850). Although both kinases are capable of interacting with and
      phosphorylating AR at Ser-213, only PIM-1L could phosphorylate Thr-850. We also
      showed that PIM-1S induced Ser-213 phosphorylation destabilizes AR by recruiting
      the ubiquitin E3 ligase Mdm2 and promotes AR degradation in a cell cycle
      dependent manner, while PIM-1L-induced Thr-850 phosphorylation stabilizes AR by
      recruiting the ubiquitin E3 ligase RNF6 and promotes AR-mediated transcription
      under low-androgen conditions. Furthermore, both PIM-1 isoforms could promote
      prostate cancer cell growth under low-androgen conditions. Our data suggest that
      these kinases regulate AR stability and transcriptional activity through
      recruitment of different functional partners in a phosphorylation-dependent
      manner. As AR turnover has been previously shown to be critical for cell cycle
      progression in prostate cancer cells, PIM-1 kinase isoforms may promote prostate
      cancer cell growth, at least in part, through modulating AR activity via distinct
      mechanisms.

PMID- 22584580
TI  - Functional regulation of sugar assimilation by N-glycan-specific interaction of
      pancreatic alpha-amylase with glycoproteins of duodenal brush border membrane.
AB  - Porcine pancreatic alpha-amylase (PPA) binds to N-linked glycans of glycoproteins
      (Matsushita, H., Takenaka, M., and Ogawa, H. (2002) J. Biol Chem., 277, 4680
      4686). Immunostaining revealed that PPA is located at the brush-border membrane
      (BBM) of enterocytes in the duodenum and that the binding is inhibited by mannan
      but not galactan, indicating that PPA binds carbohydrate-specifically to BBM. The
      ligands for PPA in BBM were identified as glycoprotein N-glycans that are
      significantly involved in the assimilation of glucose, including sucrase
      isomaltase (SI) and Na(+)/Glc cotransporter 1 (SGLT1). Binding of SI and SGLT1 in
      BBM to PPA was dose-dependent and inhibited by mannan. Using BBM vesicles, we
      found functional changes in PPA and its ligands in BBM due to the N-glycan
      specific interaction. The starch-degrading activity of PPA and maltose-degrading
      activity of SI were enhanced to 240 and 175%, respectively, while Glc uptake by
      SGLT1 was markedly inhibited by PPA at high but physiologically possible
      concentrations, and the binding was attenuated by the addition of mannose
      specific lectins, especially from Galanthus nivalis. Additionally, recombinant
      human pancreatic alpha-amylases expressed in yeast and purified by single-step
      affinity chromatography exhibited the same carbohydrate binding specificity as
      PPA in binding assays with sugar-biotinyl polymer probes. The results indicate
      that mammalian pancreatic alpha-amylases share a common carbohydrate binding
      activity and specifically bind to the intestinal BBM. Interaction with N-glycans
      in the BBM activated PPA and SI to produce much Glc on the one hand and to
      inhibit Glc absorption by enterocytes via SGLT1 in order to prevent a rapid
      increase in blood sugar on the other.

PMID- 22584582
TI  - Successive phosphorylation of p27(KIP1) protein at serine-10 and C terminus
      crucially controls its potency to inactivate Cdk2.
AB  - During the G(1)-S transition, the activity of Cdk2 is regulated by its
      association with p27(KIP1), which in rodent fibroblasts undergoes phosphorylation
      mainly at serine 10, threonine 187, and C-terminal threonine 197 by KIS, Cdk2,
      and Pim or ROCK, respectively. Recently Cdc6 the AAA+ ATPase, identified
      initially to assemble pre-replicative complexes on origins of replication and
      later to activate p21(CIP1)-inactivated Cdk2, was found also to activate p27
      bound Cdk2 but only after the bound p27 is C-terminally phosphorylated. On the
      other hand, the biological significance of the serine 10 phosphorylation remains
      elusive aside from its involvement in the stability of p27 itself. We report here
      that serine 10 phosphorylation is required for efficient C-terminal
      phosphorylation of its own by PIM and ROCK kinases and critically controls the
      potency of p27 as a Cdk2 inhibitor. In vitro, PIM1 and active ROCK1 efficiently
      phosphorylated free as well as Cdk2-bound p27 but only when the p27 was
      phosphorylated at Ser-10 in advance. Consistently, a Ser-10 nonphosphorylatable
      mutant p27 protein was not phosphorylated at the C terminus in vivo. Furthermore,
      when double-phosphorylated, free p27 was no longer a potent inhibitor of Cdk2,
      and Cdk2-bound p27 could be removed by Cdc6 to reactivate the Cdk2. Thus,
      phosphorylation at these two sites crucially controls the potency of this CDK
      inhibitor in two distinct modes.

PMID- 22584581
TI  - Balancing Arc synthesis, mRNA decay, and proteasomal degradation: maximal protein
      expression triggered by rapid eye movement sleep-like bursts of muscarinic
      cholinergic receptor stimulation.
AB  - Cholinergic signaling induces Arc/Arg3.1, an immediate early gene crucial for
      synaptic plasticity. However, the molecular mechanisms that dictate Arc mRNA and
      protein dynamics during and after cholinergic epochs are little understood. Using
      human SH-SY5Y neuroblastoma cells, we show that muscarinic cholinergic receptor
      (mAchR) stimulation triggers Arc synthesis, whereas translation-dependent RNA
      decay and proteasomal degradation strictly limit the amount and duration of Arc
      expression. Chronic application of the mAchR agonist, carbachol (Cch), induces
      Arc transcription via ERK signaling and release of calcium from IP(3)-sensitive
      stores. Arc translation requires ERK activation, but not changes in intracellular
      calcium. Proteasomal degradation of Arc (half-life ~37 min) was enhanced by
      thapsigargin, an inhibitor of the endoplasmic calcium-ATPase pump. Similar
      mechanisms of Arc protein regulation were observed in cultured rat hippocampal
      slices. Functionally, we studied the impact of cholinergic epoch duration and
      temporal pattern on Arc protein expression. Acute Cch treatment (as short as 2
      min) induces transient, moderate Arc expression, whereas continuous treatment of
      more than 30 min induces maximal expression, followed by rapid decline.
      Cholinergic activity associated with rapid eye movement sleep may function to
      facilitate long term synaptic plasticity and memory. Employing a paradigm
      designed to mimic intermittent rapid eye movement sleep epochs, we show that
      application of Cch in a series of short bursts generates persistent and maximal
      Arc protein expression. The results demonstrate dynamic, multifaceted control of
      Arc synthesis during mAchR signaling, and implicate cholinergic epoch duration
      and repetition as critical determinants of Arc expression and function in
      synaptic plasticity and behavior.

PMID- 22584583
TI  - Family matters: effect of host plant variation in chemical and mechanical
      defenses on a sequestering specialist herbivore.
AB  - Insect herbivores contend with various plant traits that are presumed to function
      as feeding deterrents. Paradoxically, some specialist insect herbivores might
      benefit from some of these plant traits, for example by sequestering plant
      chemical defenses that herbivores then use as their own defense against natural
      enemies. Larvae of the butterfly species Battus philenor (L.) (Papilionidae)
      sequester toxic alkaloids (aristolochic acids) from their Aristolochia host
      plants, rendering larvae and adults unpalatable to a broad range of predators. We
      studied the importance of two putative defensive traits in Aristolochia erecta:
      leaf toughness and aristolochic acid content, and we examined the effect of intra
      and interplant chemical variation on the chemical phenotype of B. philenor
      larvae. It has been proposed that genetic variation for sequestration ability is
      "invisible to natural selection" because intra- and interindividual variation in
      host-plant chemistry will largely eliminate a role for herbivore genetic
      variation in determining an herbivore's chemical phenotype. We found substantial
      intra- and interplant variation in leaf toughness and in the aristolochic acid
      chemistry in A. erecta. Based on field observations and laboratory experiments,
      we showed that first-instar larvae preferentially fed on less tough, younger
      leaves and avoided tougher, older leaves, and we found no evidence that
      aristolochic acid content influenced first-instar larval foraging. We found that
      the majority of variation in the amount of aristolochic acid sequestered by
      larvae was explained by larval family, not by host-plant aristolochic acid
      content. Heritable variation for sequestration is the predominant determinant of
      larval, and likely adult, chemical phenotype. This study shows that for these
      highly specialized herbivores that sequester chemical defenses, traits that offer
      mechanical resistance, such as leaf toughness, might be more important
      determinants of early-instar larval foraging behavior and development compared to
      plant chemical defenses.

PMID- 22584584
TI  - Increasing nitrogen deposition enhances post-drought recovery of grassland
      productivity in the Mongolian steppe.
AB  - Arid regions are prone to drought because annual rainfall accumulation depends on
      a few rainfall events. Natural plant communities are damaged by drought, but
      atmospheric nitrogen (N) deposition may enhance the recovery of plant
      productivity after drought. Here, we investigated the effect of increasing N
      deposition on post-drought recovery of grassland productivity in the Mongolian
      steppe, and we examined the influence of grazing in this recovery. We added
      different amounts of N to a Mongolian grassland during two sequential drought
      years (2006 and 2007) and the subsequent 3 years of normal rainfall (2008-2010)
      under grazed and nongrazed conditions. Aboveground biomass and number of shoots
      were surveyed annually for each species. Nitrogen addition increased grassland
      productivity after drought irrespective of the grazing regime. The increase in
      grassland productivity was associated with an increase in the size of an annual,
      Salsola collina, under grazed conditions, and with an increase in shoot emergence
      of a perennial, Artemisia adamsii, under nongrazed conditions. The addition of
      low N content simulating N deposition around the study area by the year 2050 did
      not significantly increase grassland productivity. Our results suggest that
      increasing N deposition can enhance grassland recovery after a drought even in
      arid environments, such as the Mongolian steppe. This enhancement may be
      accompanied by a loss of grassland quality caused by an increase in the
      unpalatable species A. adamsii and largely depends on future human activities and
      the consequent deposition of N in Mongolia.

PMID- 22584585
TI  - PSMA7 inhibits the tumorigenicity of A549 human lung adenocarcinoma cells.
AB  - The gene for proteasome subunit alpha type-7 (PSMA7) is located in chromosomal
      20q13.33, a region frequently amplified in tumor. In this study, we employed A549
      human lung adenocarcinoma cells and showed that PSMA7 inhibits the proliferation,
      tumorigenicity and invasion of A549 cells in vitro. Moreover, both gain and loss
      of function studies demonstrated that PSMA7 modulates the tumorigenicity of A549
      cells in a xenograft nude mice model. In conclusion, these results identify
      inhibitory effects associated with PSMA7 that affect the tumorigenicity of A549
      cells, suggesting PSMA7 as a potential tumor biomarker.

PMID- 22584586
TI  - A shift in the salt bridge interaction of residues D620 and E621 mediates the
      constitutive activation of Jak2-H538Q/K539L.
AB  - Jak2 mutations in the exon 14 and exon 12 regions that cause constitutive
      activation have been associated with myeloproliferative neoplasms. We have
      previously shown that a pi stacking interaction between F617 and F595 is
      important for the constitutive activation of Jak2-V617F (Gnanasambandan et al.,
      Biochemistry 49:9972-9984, 2010). Here, using a combination of molecular dynamics
      (MD) simulations and in vitro mutagenesis, we studied the molecular mechanism for
      the constitutive activation of the Jak2 exon 12 mutation, H538Q/K539L. The
      activation levels of Jak2-H538Q/K539L were found to be similar to that of Jak2
      V617F, and Jak2-H538Q/K539L/V617F. Data from MD simulations indicated a shift in
      the salt bridge interactions of D620 and E621 with K539 in Jak2-WT to R541 in
      Jak2-H538Q/K539L. When compared to Jak2-WT, K539A mutation resulted in increased
      activation, while K539D or K539E mutations diminished Jak2 activation by 50 %. In
      the context of Jak2-H538Q/K539L, R541A mutation reduced its activation by 50 %,
      while R541D and R541E mutations returned its activation levels to that of Jak2
      WT. Collectively, these results indicate that a shift in the salt bridge
      interaction of D620 and E621 with K539 in Jak2-WT to R541 in Jak2-H538Q/K539L is
      critical for constitutive activation of this Jak2 exon 12 mutant.

PMID- 22584589
TI  - Now we must work even harder.

PMID- 22584587
TI  - KLF5 and hhLIM cooperatively promote proliferation of vascular smooth muscle
      cells.
AB  - Kruppel-like factor 5 (KLF5) plays an important role in cellular proliferation
      and differentiation. In this study, we show that adenovirus-mediated
      overexpression of KLF5 increased neointimal formation, while human heart LIM
      protein (hhLIM) decreased neointimal formation following vascular injury.
      Interestingly, neointimal formation was significantly increased in the animals
      where both hhLIM and KLF5 were introduced, suggesting that KLF5 can reverse hhLIM
      function in cell proliferation on the coexpression with hhLIM. These results were
      also confirmed the cellular level. Further mechanistic studies suggested that
      PDGF-BB promoted the interaction between hhLIM and KLF5 through stimulating hhLIM
      binding to TGF-beta control element (TCE) on the cyclin E promoter in a KLF5
      dependent manner. Failure of KLF5 binding to the TCE, on the knockdown of KLF5 by
      transfecting siRNA, not only prevented the recruitment of hhLIM to the cyclin E
      promoter but also affected activation of the cyclin E promoter by KLF5. These
      data suggest that KLF5 reverses hhLIM function from anti-proliferation to pro
      proliferation through its interaction with hhLIM on the cyclin E promoter.

PMID- 22584591
TI  - Podocyte GTPases regulate kidney filter dynamics.
AB  - Our concept of the kidney filtration barrier is changing from one of a static
      sieve into one of a highly dynamic structure regulated through the motility of
      podocyte foot processes. Inactivation of the small GTPase RhoA in vitro causes
      hypermotility, whereas activation decreases motility. Wang et al. show that both
      overactivation and underactivation of RhoA lead to podocyte foot process
      effacement and proteinuria in vivo. These data suggest that podocyte health
      requires a well-controlled balance between the two extremes.

PMID- 22584592
TI  - Alternate-day dialysis may be needed for hemodialysis patients.
AB  - Zhang et al. studied the relationship between day of the week and all-cause and
      cardiovascular mortality in the United States, Europe, and Japan. The study
      confirms findings of studies of US patients that risk of all-cause and cardiac
      mortality is higher after a long interdialytic interval, and shows that this is
      also true in Europe and Japan. Alternate-day dialysis may improve patient
      survival on hemodialysis, but randomized trials are necessary to establish a new
      schedule.

PMID- 22584593
TI  - Calcium balance in chronic kidney disease: walking the tightrope.
AB  - Calcium supplements for prevention and treatment of mineral and bone disorders in
      chronic kidney disease (CKD) have been alternately praised and damned. Clinical
      evidence in favor of either attitude has been lacking. The calcium balance study
      by Spiegel and Brady in patients with late stage 3 and stage 4 CKD suggests that
      CKD subjects ingesting 2000 mg of elemental calcium per day are in marked
      positive balance. Methodological limitations such as unproven steady state
      warrant caution and confirmatory studies.

PMID- 22584595
TI  - European guidelines on when to start dialysis: check the facts first before
      commenting.

PMID- 22584596
TI  - Peritonitis rates with biocompatible and conventional peritoneal dialysis
      solutions.

PMID- 22584599
TI  - Chronic kidney disease in Pakistan: an under-recognized public health problem.

PMID- 22584600
TI  - U-shaped effect of eGFR and mortality.

PMID- 22584601
TI  - Uremic frost.

PMID- 22584602
TI  - Porous magnesium carboxylate framework: synthesis, X-ray crystal structure, gas
      adsorption property and heterogeneous catalytic aldol condensation reaction.
AB  - A new three-dimensional alkaline-earth metal-organic framework (MOF) compound,
      [Mg(Pdc)(H(2)O)](n) (1) (H(2)Pdc = pyridine-2,5-dicarboxylic acid), has been
      synthesized and structurally characterized by single crystal X-ray diffraction
      analysis. Compound 1 features a 3D porous framework afforded by the Mg(2)-diad
      centers through formation of interconnected chair like structural motifs. A
      nitrogen adsorption study confirms the microporosity of compound 1 with a BET
      surface area of 211 +/- 12 m(2) g(-1). Upon dehydration, the BET surface area of
      1 is enhanced to a value of 463 +/- 36 m(2) g(-1) due to removal of coordinated
      water molecule. After rehydration, the compound reverts to its original form as
      evidenced by powder X-ray diffraction and IR spectroscopic analysis and N(2)
      sorption measurement. Compound 1 retains its pore structure with a variable BET
      surface area in several cycles of dehydration and rehydration processes
      indicating robustness of the framework in [Mg(Pdc)(H(2)O)](n) (1). Compound 1
      catalyzes the aldol condensation reactions of various aromatic aldehydes with
      acetone and cyclohexanone in heterogeneous conditions. Notably, the catalytic
      activity of the compound is enhanced upon dehydration. The catalyst can be
      recycled and reused several times without significant loss of activity.

PMID- 22584603
TI  - Maternal and neonatal outcomes following methadone substitution during pregnancy.
AB  - PURPOSE: To assess the maternal and neonatal outcomes of pregnant women enrolled
      on a Methadone Substitution Programme (MSP). DESIGN: Retrospective cohort study.
      SETTING: Maternity unit of a London teaching hospital and tertiary referral
      centre. SUBJECTS: Pregnant women on a MSP whose antenatal care and delivery was
      at St Thomas' Hospital (STH) between January 2005 and March 2008. Controls were
      non-MSP mothers closely matched for age, parity and delivery date during the same
      period. METHODS: Maternal data was collected from the Liaison Antenatal Drugs and
      Alcohol Service clinic records and the STH Maternity Unit's computerised
      database. Neonatal data was extracted from the STH Neonatal database (part of the
      UK National Neonatal database). OUTCOME MEASURES: Maternal profiles (age,
      gravidity, parity, ethnicity, BMI, smoking and alcohol history, relationship and
      employment history), pregnancy details and mode of delivery. Neonatal outcome
      measures to include gestation age at delivery, birth weight, head circumference,
      admission rates and length of stay on Special Care Baby Unit plus Neonatal
      Abstinence Syndrome (NAS) rates, scoring and treatment. RESULTS: Compared to the
      non-MSP mothers (n = 88) the MSP group (n = 44) booked later and had a higher
      incidence of smoking (6.8 vs. 84.1 %), alcohol consumption (10.2 vs. 34.1 %). As
      a group, they had adverse social background. The MSP group had a higher relative
      risk (RR) of premature delivery [RR = 2.5, 95% confidence interval (CI) 1.66
      3.88] and had lower birth weight babies (adjusted RR = 2.2; 95% CI 1.31-3.71)
      with smaller head circumferences (adjusted RR 1.9; 95% CI 1.06-3.38). NAS
      occurred in 27 % (95% CI 15.0-42.8) of the MSP group. There was no difference in
      congenital abnormality between the two groups, but caesarean section rate was
      higher in the control group. CONCLUSION: Opiate-addicted mothers have adverse
      perinatal outcomes even on MSPs. In addition to the drug effect associated
      social, relationship and accommodation problems should also be addressed as they
      may affect the outcome. Pregnancy care for these women needs to continue to
      develop to improve overall outcomes.

PMID- 22584604
TI  - Progesterone combined with beta human chorionic gonadotropin measurements and
      threatened miscarriage.

PMID- 22584605
TI  - Concepts on childhood microcrania: a clinical overview for the neurosurgeon who
      is evaluating a child with a small head.
AB  - PURPOSE: Infants and children with microcrania are referred to pediatric
      neurosurgeons for evaluation and treatment of possible craniosynostosis and other
      disorders. We present an approach to these children to facilitate the appropriate
      clinical evaluation and management. METHODS: We reviewed our experience and the
      literature on infants and children with microcephaly, and developed a management
      strategy for these children when seen in the University of Florida Division of
      Pediatric Neurosurgery. RESULTS: We request the same sex parent to accompany the
      child for their consultation. If the head circumference of the child matches that
      of the same sex parent in percentiles, and there are no other abnormalities, no
      further assessment or studies are performed. If there is a disproportionate head
      size to that of the same sex parent and/or other structural abnormalities are
      present, the child is referred to clinical genetics for further assessment.
      CONCLUSIONS: When patients are referred to pediatric neurosurgery for
      microcrania, their head size should be compared to that of the same sex parent.
      This will facilitate the diagnosis of familial microcephaly, and if no other
      abnormalities are noted, no further studies or surgical interventions are
      necessary.

PMID- 22584607
TI  - The influence of mechanical stimulation on osteoclast localization in the mouse
      maxilla: bone histomorphometry and finite element analysis.
AB  - The mechanism of traumatic bone resorption in the denture-bearing bone has not
      yet been established with regard to the osteoclastic activity in relation to the
      mechanical stimulus. The purpose of this study was to clarify whether osteoclast
      appearance in maxilla depends on the strain intensity, using the murine loading
      model. The maxillary palate of thirteen-week-old male C57BL/6 mice was subjected
      to continuous pressure of 2 kPa (low stimulation, n = 4) or 7 kPa (high
      stimulation, n = 4) for 30 min/day for 7 consecutive days, and the mice were
      sacrificed after the last loading. The control group underwent the same protocol
      without load (n = 4). An animal-specific finite element model was constructed
      based on morphology and characteristics obtained from the micro-CT data and used
      to calculate the strain intensity of the bone. The bone histomorphometric
      technique revealed significant reduction of cortical bone volume and significant
      increase of bone resorption parameters such as osteoclast number in the bone
      tissue under the loading contact in comparison to the control (p < 0.05). The
      osteoclasts were observed in the subsurface region adjacent to the loading
      contact and the peripheral region of the marrow space in the intracortical region
      of the cortical bone in the mouse maxilla in both stimulation groups. An average
      of more than 90 % of the osteoclasts was observed in the areas with strain
      intensity higher than 85.0MU strain for the high stimulation group. The result
      suggests that the osteoclastic resorption is location-dependent and is also
      sensitive to the local strain intensity.

PMID- 22584608
TI  - Numerical modelling of the angiogenesis process in wound contraction.
AB  - Angiogenesis consists of the growth of new blood vessels from the pre-existing
      vasculature. This phenomenon takes place in several biological processes,
      including wound healing. In this work, we present a mathematical model of
      angiogenesis applied to skin wound healing. The developed model includes
      biological (capillaries and fibroblasts), chemical (oxygen and angiogenic growth
      factor concentrations) and mechanical factors (cell traction forces and
      extracellular matrix deformation) that influence the evolution of the healing
      process. A novelty from previous works, apart from the coupling of angiogenesis
      and wound contraction, is the more realistic modelling of skin as a hyperelastic
      material. Large deformations are addressed using an updated Lagrangian approach.
      The coupled non-linear model is solved with the finite element method, and the
      process is studied over two wound geometries (circular and elliptical) of the
      same area. The results indicate that the elliptical wound vascularizes two days
      earlier than the circular wound but that they experience a similar contraction
      level, reducing its size by 25 %.

PMID- 22584606
TI  - Highly sensitive single-fibril erosion assay demonstrates mechanochemical switch
      in native collagen fibrils.
AB  - It has been established that the enzyme susceptibility of collagen, the
      predominant load-bearing protein in vertebrates, is altered by applied tension.
      However, whether tensile force increases or decreases the susceptibility to
      enzyme is a matter of contention. It is critical to establish a definitive
      understanding of the direction and magnitude of the force versus catalysis rate
      (k C ) relationship if we are to properly interpret connective tissue
      development, growth, remodeling, repair, and degeneration. In this investigation,
      we examine collagen/enzyme mechanochemistry at the smallest scale structurally
      relevant to connective tissue: the native collagen fibril. A single-fibril
      mechanochemical erosion assay with nN force resolution was developed which
      permits detection of the loss of a few layers of monomer from the fibril surface.
      Native type I fibrils (bovine) held at three levels of tension were exposed to
      Clostridium histolyticum collagenase A. Fibrils held at zero-load failed rapidly
      and consistently (20 min) while fibrils at 1.8 pN/monomer failed more slowly (35
      55 min). Strikingly, fibrils at 23.9 pN/monomer did not exhibit detectable
      degradation. The extracted force versus k C data were combined with previous
      single-molecule results to produce a "master curve" which suggests that collagen
      degradation is governed by an extremely sensitive mechanochemical switch.

PMID- 22584610
TI  - Regional North American annual meeting of the World Federation of Neurology -
      Research Group on Neuroepidemiology. Louisiana State University, New Orleans,
      La., April 27, 2012.

PMID- 22584616
TI  - Intercalation of organic sensitisers into layered europium hydroxide and enhanced
      luminescence property.
AB  - Two organic sensitisers 4-biphenylcarboxylate (BPC) and terephthalate (TA) were
      intercalated into the gallery of layered europium hydroxide (LEuH). PL spectra
      tests indicated that BPC markedly enhanced the red luminescence of Eu(3+) due to
      efficient energy transfer between BPC and Eu(3+), forming a contrast to
      intercalated TA and the starting NO(3)(-) anions in the gallery. The energy level
      matching of the organic guests and Eu(3+) was also discussed to explain the
      energy transfer from sensitiser to Eu(3+).

PMID- 22584609
TI  - Extracellular matrix and the mechanics of large artery development.
AB  - The large, elastic arteries, as their name suggests, provide elastic distention
      and recoil during the cardiac cycle in vertebrate animals. The arteries are
      distended from the pressure of ejecting blood during the active contraction of
      the left ventricle (LV) during systole and recoil to their original dimensions
      during relaxation of the LV during diastole. The cyclic distension occurs with
      minimal energy loss, due to the elastic properties of one of the major structural
      extracellular matrix (ECM) components, elastin. The maximum distension is limited
      to prevent damage to the artery by another major ECM component, collagen. The mix
      of ECM components in the wall largely determines the passive mechanical behavior
      of the arteries and the subsequent load on the heart during systole. While much
      research has focused on initial artery formation, there has been less attention
      on the continuing development of the artery to produce the mature composite wall
      complete with endothelial cells (ECs), smooth muscle cells (SMCs), and the
      necessary mix of ECM components for proper cardiovascular function. This review
      focuses on the physiology of large artery development, including SMC
      differentiation and ECM production. The effects of hemodynamic forces and ECM
      deposition on the evolving arterial structure and function are discussed. Human
      diseases and mouse models with genetic mutations in ECM proteins that affect
      large artery development are summarized. A review of constitutive models and
      growth and remodeling theories is presented, along with future directions to
      improve understanding of ECM and the mechanics of large artery development.

PMID- 22584617
TI  - The Triple I Hypothesis: taking another('s) perspective on executive dysfunction
      in autism.
AB  - The executive dysfunction theory attempts to explain not only the repetitive
      behaviours but also the socio-communicative difficulties in autism. While it is
      clear that some individuals with autism perform poorly on certain executive
      function tasks, it remains unclear what underlies these impairments. The most
      consistent and striking difficulties are seen on tasks that are open-ended in
      structure, lack explicit instructions and involve arbitrary rules. I propose that
      impairment on such tasks is not due to executive dysfunction; instead, poor
      performance results from difficulties forming an implicit understanding of the
      experimenter's expectations for the task, resulting in egocentric and
      idiosyncratic behaviour. These difficulties in taking another's perspective may
      be explained parsimoniously by the mentalising difficulties robustly demonstrated
      to exist in autism.

PMID- 22584618
TI  - Plasma methionine sulfoxide in persons with familial Alzheimer's disease
      mutations.
AB  - BACKGROUND: Convergent evidence suggests that oxidative stress plays a central
      role in the pathology of Alzheimer's disease (AD). We asked if consequently,
      oxidation of methionine residues to methionine sulfoxide (MetO) was increased in
      plasma proteins of persons carrying familial AD (FAD) mutations. METHODS: Plasma
      was collected from 31 persons from families harboring PSEN1 or APP mutations.
      Using Western blot analysis with a novel anti-MetO polyclonal antibody, MetO
      levels were measured and compared between FAD mutation carriers (MCs) and non
      mutation carrying (NCs) kin. RESULTS: A MetO-positive 120-kDa gel band
      distinguished FAD MCs and NCs (mean 11.4 +/- 2.8 vs. 4.0 +/- 3.1, p = 0.02). In a
      subset of subjects for whom both measurements were available, MetO levels
      correlated well with plasma F2-isoprostane (r = 0.81, p < 0.001) and superoxide
      dismutase 1 (r = 0.52, p = 0.004) levels. CONCLUSION: Our data provide evidence
      for elevated MetO levels in persons carrying FAD mutations that correlate with
      other indices of oxidative stress and suggest that plasma oxidative stress
      markers may be useful for diagnosis of AD.

PMID- 22584619
TI  - Single-row versus double-row arthroscopic repair in the treatment of rotator cuff
      tears: a prospective randomized clinical study.
AB  - PURPOSE: The purpose of this study was to compare arthroscopic rotator cuff
      repair with single-row and double-row techniques because research has
      demonstrated the superiority of double-row repair from a biological and
      mechanical point of view but there is no evidence of clinical superiority.
      METHODS: A total of 160 patients with a full-thickness rotator cuff tear
      underwent arthroscopic repair with suture anchors. They were randomised into two
      groups of 80 patients according to the repair technique: single-row (group 1) and
      double-row (group 2). Results were evaluated by use of the University of
      California, Los Angeles (UCLA), American Shoulder and Elbow Surgeons (ASES) and
      Constant questionnaires, the Shoulder Strength Index (SSI) and range of motion.
      Follow-up time was two years. Magnetic resonance imaging (MRI) studies were
      performed on each shoulder preoperatively and two years after repair. RESULTS:
      One hundred per cent of the patients were followed up. All measurements showed
      significant improvement compared with the preoperative status. The UCLA score
      showed significant improvement in group 2. In over 30-mm tears UCLA and ASES
      showed significant differences. SSI showed significant improvement in group 2.
      Range of motion showed significant improvements in flexion and abduction in group
      2. In under 30-mm tears group 2 showed also significant improvement in internal
      and external rotation. In MRI studies there were no significant differences.
      CONCLUSIONS: At two years follow-up the double-row repair technique showed a
      significant difference in clinical outcome compared with single-row repair and
      this was even more significative in over 30-mm tears. No MRI differences were
      observed.

PMID- 22584620
TI  - Comments on Reito et al.: Assessment of inter- and intra-observer reliability in
      the determination of radiographic version and inclination of the cup in metal-on
      metal hip resurfacing.

PMID- 22584621
TI  - Prospects and limitations of full-text index structures in genome analysis.
AB  - The combination of incessant advances in sequencing technology producing large
      amounts of data and innovative bioinformatics approaches, designed to cope with
      this data flood, has led to new interesting results in the life sciences. Given
      the magnitude of sequence data to be processed, many bioinformatics tools rely on
      efficient solutions to a variety of complex string problems. These solutions
      include fast heuristic algorithms and advanced data structures, generally
      referred to as index structures. Although the importance of index structures is
      generally known to the bioinformatics community, the design and potency of these
      data structures, as well as their properties and limitations, are less
      understood. Moreover, the last decade has seen a boom in the number of variant
      index structures featuring complex and diverse memory-time trade-offs. This
      article brings a comprehensive state-of-the-art overview of the most popular
      index structures and their recently developed variants. Their features,
      interrelationships, the trade-offs they impose, but also their practical
      limitations, are explained and compared.

PMID- 22584622
TI  - The catalytic cycle for ribonucleotide incorporation by human DNA Pol lambda.
AB  - Although most DNA polymerases discriminate against ribonucleotide triphosphaets
      (rNTPs) during DNA synthesis, recent studies have shown that large numbers of
      ribonucleotides are incorporated into the eukaryotic nuclear genome. Here, we
      investigate how a DNA polymerase can stably incorporate an rNTP. The X-ray
      crystal structure of a variant of human DNA polymerase lambda reveals that the
      rNTP occupies the nucleotide binding pocket without distortion of the active
      site, despite an unfavorable interaction between the 2'-O and Tyr505 backbone
      carbonyl. This indicates an energetically unstable binding state for the rNTP,
      stabilized by additional protein-nucleotide interactions. Supporting this idea is
      the 200-fold lower catalytic efficiency for rNTP relative to deoxyribonucleotide
      triphosphate (dNTP) incorporation, reflecting a higher apparent Km value for the
      rNTP. Furthermore, distortion observed in the structure of the post-catalytic
      product complex suggests that once the bond between the alpha- and beta
      phosphates of the rNTP is broken, the unfavorable binding state of the
      ribonucleotide cannot be maintained. Finally, structural and biochemical
      evaluation of dNTP insertion onto an ribonucleotide monophosphate (rNMP)
      terminated primer indicates that a primer-terminal rNMP does not impede
      extension. The results are relevant to how ribonucleotides are incorporated into
      DNA in vivo, during replication and during repair, perhaps especially in non
      proliferating cells when rNTP:dNTP ratios are high.

PMID- 22584623
TI  - Thermodynamics of the multi-stage DNA lesion recognition and repair by
      formamidopyrimidine-DNA glycosylase using pyrrolocytosine fluorescence--stopped
      flow pre-steady-state kinetics.
AB  - Formamidopyrimidine-DNA glycosylase, Fpg protein from Escherichia coli, initiates
      base excision repair in DNA by removing a wide variety of oxidized lesions. In
      this study, we perform thermodynamic analysis of the multi-stage interaction of
      Fpg with specific DNA-substrates containing 7,8-dihydro-8-oxoguanosine (oxoG), or
      tetrahydrofuran (THF, an uncleavable abasic site analog) and non-specific (G) DNA
      ligand based on stopped-flow kinetic data. Pyrrolocytosine, highly fluorescent
      analog of the natural nucleobase cytosine, is used to record multi-stage DNA
      lesion recognition and repair kinetics over a temperature range (10-30 degrees
      C). The kinetic data were used to obtain the standard Gibbs energy, enthalpy and
      entropy of the specific stages using van't Hoff approach. The data suggest that
      not only enthalpy-driven exothermic oxoG recognition, but also the desolvation
      accompanied entropy-driven enzyme-substrate complex adjustment into the
      catalytically active state play equally important roles in the overall process.

PMID- 22584625
TI  - A new strategy to reduce allelic bias in RNA-Seq readmapping.
AB  - Accurate estimation of expression levels from RNA-Seq data entails precise
      mapping of the sequence reads to a reference genome. Because the standard
      reference genome contains only one allele at any given locus, reads overlapping
      polymorphic loci that carry a non-reference allele are at least one mismatch away
      from the reference and, hence, are less likely to be mapped. This bias in read
      mapping leads to inaccurate estimates of allele-specific expression (ASE). To
      address this read-mapping bias, we propose the construction of an enhanced
      reference genome that includes the alternative alleles at known polymorphic loci.
      We show that mapping to this enhanced reference reduced the read-mapping biases,
      leading to more reliable estimates of ASE. Experiments on simulated data show
      that the proposed strategy reduced the number of loci with mapping bias by >= 63%
      when compared with a previous approach that relies on masking the polymorphic
      loci and by >= 18% when compared with the standard approach that uses an
      unaltered reference. When we applied our strategy to actual RNA-Seq data, we
      found that it mapped up to 15% more reads than the previous approaches and
      identified many seemingly incorrect inferences made by them.

PMID- 22584624
TI  - BIM promoter directly targeted by EBNA3C in polycomb-mediated repression by EBV.
AB  - Detailed analyses of the chromatin around the BIM promoter has revealed that
      latent Epstein-Barr virus (EBV) triggers the recruitment of polycomb repressive
      complex 2 (PRC2) core subunits and the trimethylation of histone H3 lysine 27
      (H3K27me3) at this locus. The recruitment is absolutely dependent on nuclear
      proteins EBNA3A and EBNA3C; what is more, epitope-tagged EBNA3C could be shown
      bound near the transcription start site (TSS). EBV induces no consistent changes
      in the steady-state expression of PRC2 components, but lentivirus delivery of
      shRNAs against PRC2 and PRC1 subunits disrupted EBV repression of BIM. The
      activation mark H3K4me3 is largely unaltered at this locus irrespective of
      H3K27me3 status, suggesting the establishment of a 'bivalent' chromatin domain.
      Consistent with the 'poised' nature of these domains, RNA polymerase II (Pol II)
      occupancy was not altered by EBV at the BIM TSS, but analysis of phospho-serine 5
      on Pol II indicated that EBNA3A and EBNA3C together inhibit initiation of BIM
      transcripts. B cell lines carrying EBV encoding a conditional EBNA3C-oestrogen
      receptor-fusion revealed that this epigenetic repression of BIM was reversible,
      but took more than 3 weeks from when EBNA3C was inactivated.

PMID- 22584626
TI  - Tracing the path of DNA substrates in active Tetrahymena telomerase holoenzyme
      complexes: mapping of DNA contact sites in the RNA subunit.
AB  - Telomerase, the enzyme that extends single-stranded telomeric DNA, consists of an
      RNA subunit (TER) including a short template sequence, a catalytic protein (TERT)
      and accessory proteins. We used site-specific UV cross-linking to map the binding
      sites for DNA primers in TER within active Tetrahymena telomerase holoenzyme
      complexes. The mapping was performed at single-nucleotide resolution by a novel
      technique based on RNase H digestion of RNA-DNA hybrids made with overlapping
      complementary oligodeoxynucleotides. These data allowed tracing of the DNA path
      through the telomerase complexes from the template to the TERT binding element
      (TBE) region of TER. TBE is known to bind TERT and to be involved in the template
      5'-boundary definition. Based on these findings, we propose that upstream
      sequences of each growing telomeric DNA chain are involved in regulation of its
      growth arrest at the 5'-end of the RNA template. The upstream DNA-TBE interaction
      may also function as an anchor for the subsequent realignment of the 3'-end of
      the DNA with the 3'-end of the template to enable initiation of synthesis of a
      new telomeric repeat.

PMID- 22584627
TI  - PhiSpy: a novel algorithm for finding prophages in bacterial genomes that
      combines similarity- and composition-based strategies.
AB  - Prophages are phages in lysogeny that are integrated into, and replicated as part
      of, the host bacterial genome. These mobile elements can have tremendous impact
      on their bacterial hosts' genomes and phenotypes, which may lead to strain
      emergence and diversification, increased virulence or antibiotic resistance.
      However, finding prophages in microbial genomes remains a problem with no
      definitive solution. The majority of existing tools rely on detecting genomic
      regions enriched in protein-coding genes with known phage homologs, which hinders
      the de novo discovery of phage regions. In this study, a weighted phage detection
      algorithm, PhiSpy was developed based on seven distinctive characteristics of
      prophages, i.e. protein length, transcription strand directionality, customized
      AT and GC skew, the abundance of unique phage words, phage insertion points and
      the similarity of phage proteins. The first five characteristics are capable of
      identifying prophages without any sequence similarity with known phage genes.
      PhiSpy locates prophages by ranking genomic regions enriched in distinctive phage
      traits, which leads to the successful prediction of 94% of prophages in 50
      complete bacterial genomes with a 6% false-negative rate and a 0.66% false
      positive rate.

PMID- 22584628
TI  - Improved functional outcomes for major trauma patients in a regionalized,
      inclusive trauma system.
AB  - OBJECTIVE: To describe outcomes of major trauma survivors managed in an organized
      trauma system, including the association between levels of care and outcomes over
      time. BACKGROUND: Trauma care systems aim to reduce deaths and disability.
      Studies have found that regionalization of trauma care reduces mortality but the
      impact on quality of survival is unknown. Evaluation of a trauma system should
      include mortality and morbidity. METHODS: Predictors of 12-month functional
      (Glasgow Outcome Scale-Extended) outcomes after blunt major trauma (Injury
      Severity Score >15) in an organized trauma system were explored using ordered
      logistic regression for the period October 2006 to June 2009. Data from the
      population-based Victorian State Trauma Registry were used. RESULTS: There were
      4986 patients older than 18 years. In-hospital mortality decreased from 11.9% in
      2006-2007 to 9.9% in 2008-2009. The follow-up rate at 12 months was 86% (n =
      3824). Eighty percent reported functional limitations. Odds of better functional
      outcome increased in the 2007-2008 [adjusted odds ratio (AOR): 1.22; 95% CI:
      1.05, 1.41] and 2008-2009 (AOR: 1.16; 95% CI: 1.01, 1.34) years compared with
      2006-2007. Cases managed at major trauma services (MTS) achieved better
      functional outcome (AOR: 1.22; 95% CI: 1.03, 1.45). Female gender, older age, and
      lower levels of education demonstrated lower adjusted odds of better outcome.
      CONCLUSIONS: Despite an annual decline in mortality, risk-adjusted functional
      outcomes improved over time, and cases managed at MTS (level-1 trauma centers)
      demonstrated better functional outcomes. The findings provide early evidence that
      this inclusive, regionalized trauma system is achieving its aims.

PMID- 22584629
TI  - The effect of prophylactic transpapillary pancreatic stent insertion on
      clinically significant leak rate following distal pancreatectomy: results of a
      prospective controlled clinical trial.
AB  - OBJECTIVE: To determine whether prophylactic pancreatic duct stenting reduces
      pancreatic fistula (PF) formation after distal pancreatectomy (DP). BACKGROUND:
      PF causes major morbidity after DP. Transpapillary pancreatic stenting has been
      proposed to be beneficial in treating established PF and also, prophylactically,
      to reduce the risk for PF after DP. PATIENTS AND METHODS: Patients scheduled for
      DP during October 2006 to December 2010 were assessed and, if eligible,
      randomized to DP without (DP) or with stenting before transection of the neck of
      the gland (DP + stent). DP procedure was standardized and the follow-up period
      included the first 30 postoperative days. The outcomes were assessed according to
      the intention to treat analysis principle. RESULTS: : Sixty-four patients were
      assessed and 58 were randomized to either DP (n = 29) or DP + stent (n = 29).
      Mean +/- SD operation time for DP was 218.8 +/- 94.1 compared to 283.3 +/- 131.9
      for DP + stent (P = 0.052). Clinically significant PF (ISGPF [The International
      Study Group on Pancreatic Fistula] classification Grade B or C) occurred in 6 DP
      (22.2%) and 11 (42.3%) DP + stent patients (odds ratio: 2.57, 95% confidence
      interval 0.78-8.48; P = 0.122). The mean hospital stay for patients without stent
      was 13.4 +/- 6.4 days compared to 19.4 +/- 14.4 days for those provided with a
      pancreatic stent (P = 0.071). CONCLUSIONS: The results from this trial show that
      prophylactic pancreatic stenting does not reduce PF when performing a
      standardized resection of the body and tail of the pancreas. The trial was
      registered at clinicaltrials.gov NCT00500968.

PMID- 22584630
TI  - Identifying patients at high risk for venous thromboembolism requiring treatment
      after outpatient surgery.
AB  - OBJECTIVE: To identify independent predictors of 30-day venous thromboembolism
      (VTE) events requiring treatment after outpatient surgery. BACKGROUND: An
      increasing proportion of surgical procedures are performed in the outpatient
      setting. The incidence of VTE requiring treatment after outpatient surgery is
      unknown. METHODS: Prospective observational cohort study using the American
      College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP)
      database from 2005 to 2009. Adult patients who had outpatient surgery or surgery
      with subsequent 23-hour observation were included. The main outcome measure was
      30-day VTE requiring treatment. Patients were randomly assigned to derivation (N
      = 173,501) or validation (N = 85,730) cohorts. Logistic regression examined
      independent risk factors for 30-day VTE. A weighted risk index was created and
      applied to the validation cohort. Stratified analyses examined 30-day VTE by risk
      level. RESULTS: Thirty-day incidence of VTE for the overall cohort was 0.15%.
      Independent risk factors included current pregnancy (adjusted odds ratio [OR] =
      7.80, P = 0.044), active cancer (OR = 3.66, P = 0.005), age 41 to 59 years (OR =
      1.72, P = 0.008), age 60 years or more (OR = 2.48, P < 0.001), body mass index 40
      kg/m or higher (OR = 1.81, P = 0.015), operative time 120 minutes or more (OR =
      1.69, P = 0.027), arthroscopic surgery (OR = 5.16, P < 0.001), saphenofemoral
      junction surgery (OR = 13.20, P < 0.001), and venous surgery not involving the
      great saphenous vein (OR = 15.61, P < 0.001). The weighted risk index identified
      a 20-fold variation in 30-day VTE between low (0.06%) and highest risk (1.18%)
      patients. CONCLUSIONS: Thirty-day VTE risk after outpatient surgery can be
      quantified using a weighted risk index. The risk index identifies a high-risk
      subgroup of patients with 30-day VTE rates of 1.18%.

PMID- 22584631
TI  - Surgery for primary hyperparathyroidism: are the consensus guidelines being
      followed?
AB  - OBJECTIVE: To determine parathyroidectomy (PTx) rates in patients who satisfy the
      consensus guidelines for surgical treatment of primary hyperparathyroidism
      (PHPT). BACKGROUND: Surgery for PHPT is recommended for all symptomatic patients
      and select asymptomatic patients meeting established consensus criteria.
      Adherence to the consensus guidelines has not been examined systematically,
      because of inadequate information regarding patients managed nonoperatively.
      METHODS: All nonuremic patients with PHPT during the period 1995-2008 were
      identified using the Kaiser Permanente-Southern California laboratory database,
      encompassing 3.5 million individuals annually. Multivariate logistic regression
      was used to examine predictors of PTx. RESULTS: We found 3388 patients with PHPT,
      of whom 265 (8%) were symptomatic (nephrolithiasis). Nephrolithiasis was
      predictive of PTx (OR 2.94 vs asymptomatic), with 51% of symptomatic patients
      undergoing surgery. Among asymptomatic patients, the proportion meeting consensus
      criteria was 39% during the early period (1995-2002) and 51% during the late
      period (2003-2008). The PTx rate for these patients exceeded that for
      asymptomatic patients not meeting consensus criteria but remained low (early 44%
      vs 19%, P < 0.0001; late 39% vs 16%, P < 0.0001). The following individual
      criteria were predictive of PTx: calcium >11.5 mg/dL (OR 2.27), hypercalciuria
      (OR 3.28, P < 0.0001), and age < 50 years (OR 1.54, P < 0.0001). However, the
      absolute PTx rates associated with satisfaction of these criteria were in the 50%
      range. Bone density scores did not influence likelihood of PTx and renal
      impairment predicted against PTx (OR 0.35, P < 0.0001). CONCLUSIONS: The
      consensus guidelines regarding PHPT have not been followed in our study
      population. PTx appears to be underutilized in both asymptomatic and symptomatic
      patients.

PMID- 22584632
TI  - A quality improvement study on avoidable stressors and countermeasures affecting
      surgical motor performance and learning.
AB  - OBJECTIVE: To explore how the 2 most important components of surgical performance
      -speed and accuracy-are influenced by different forms of stress and what the
      impact of music is on these factors. BACKGROUND: On the basis of a recently
      published pilot study on surgical experts, we designed an experiment examining
      the effects of auditory stress, mental stress, and music on surgical performance
      and learning and then correlated the data psychometric measures to the role of
      music in a novice surgeon's life. METHODS: Thirty-one surgeons were recruited for
      a crossover study. Surgeons were randomized to 4 simple standardized tasks to be
      performed on the SurgicalSIM VR laparoscopic simulator (Medical Education
      Technologies, Inc, Sarasota, FL), allowing exact tracking of speed and accuracy.
      Tasks were performed under a variety of conditions, including silence, dichotic
      music (auditory stress), defined classical music (auditory relaxation), and
      mental loading (mental arithmetic tasks). Tasks were performed twice to test for
      memory consolidation and to accommodate for baseline variability. Performance was
      correlated to the brief Musical Experience Questionnaire (MEQ). RESULTS: Mental
      loading influences performance with respect to accuracy, speed, and recall more
      negatively than does auditory stress. Defined classical music might lead to
      minimally worse performance initially but leads to significantly improved memory
      consolidation. Furthermore, psychologic testing of the volunteers suggests that
      surgeons with greater musical commitment, measured by the MEQ, perform worse
      under the mental loading condition. CONCLUSIONS: Mental distraction and auditory
      stress negatively affect specific components of surgical learning and
      performance. If used appropriately, classical music may positively affect
      surgical memory consolidation. It also may be possible to predict surgeons'
      performance and learning under stress through psychological tests on the role of
      music in a surgeon's life. Further investigation is necessary to determine the
      cognitive processes behind these correlations.

PMID- 22584633
TI  - Identification of markers linked to the race Ug99 effective stem rust resistance
      gene Sr28 in wheat (Triticum aestivum L.).
AB  - Wheat stem rust caused by Puccinia graminis f. sp. tritici can cause devastating
      yield losses in wheat. Over the past several decades, stem rust has been
      controlled worldwide through the use of genetic resistance. Stem rust race TTKSK
      (Ug99), first detected in Uganda in 1998, threatens global wheat production
      because of its unique virulence combination. As the majority of the currently
      grown cultivars and advanced breeding lines are susceptible to race TTKSK,
      sources of resistance need to be identified and characterized to facilitate their
      use in agriculture. South Dakota breeding line SD 1691 displayed resistance to
      race TTKSK in the international wheat stem rust nursery in Njoro, Kenya. Seedling
      screening of progeny derived from SD 1691 crossed to susceptible LMPG-6 indicated
      that a single resistance gene was present. Allelism and race-specificity tests
      indicated the stem rust resistance gene in SD 1691 was Sr28. The chromosome arm
      location of Sr28 was previously demonstrated to be 2BL. We identified molecular
      markers linked to Sr28 and validated this linkage in two additional populations.
      Common spring wheat cultivars in the central United States displayed allelic
      diversity for markers flanking Sr28. These markers could be used to select for
      Sr28 in breeding populations and for combining Sr28 with other stem rust
      resistance genes.

PMID- 22584634
TI  - Valproate induces epigenetic modifications in lymphomonocytes from epileptic
      patients.
AB  - Valproate (VPA) is an anti-epileptic and mood-stabilizing drug with a broad range
      of action and which mechanism of action still remains in part elusive. Recently
      the discovery that VPA modifies the epigenome increasing the transcriptional rate
      of target genes raises the issue of understanding the exact role of this
      mechanism. In this work we tested the possibility that VPA could modify the
      epigenome of lymphomonocytes (PBMC) obtained from epileptic patients chronically
      treated in monotherapy with VPA and phenobarbital. Acetyl-histone H3 expression
      was assessed by western blotting and global DNA methylation by incorporation of
      [3H]dCTP. A significant increase in histone acetylation and a correlated decrease
      of global DNA methylation were shown at VPA therapeutically relevant plasma
      concentrations. This effect was drug-related, since it was not demonstrated in
      PBMC obtained from phenobarbital-treated patients. Moreover, a VPA dose-response
      curve was performed on PBMC obtained from healthy controls, demonstrating an
      increase of acetyl-histone H3 content. We suggest that the epigenetic properties
      of VPA expressed on PBMC at these concentrations might be operative in different
      tissues, with possible implications for the field of neuropsychiatric disorders.

PMID- 22584635
TI  - Are changes in conduit artery function associated with intima-medial thickness in
      young subjects?
AB  - BACKGROUND: Impaired brachial artery endothelial function, assessed by flow
      mediated dilation (FMD), provides a strong prognostic index of cardiovascular
      events in asymptomatic adults and those with cardiovascular disease. However, the
      relationship between FMD and carotid intima-medial thickness (cIMT) in young
      people is unknown. We hypothesized that impaired FMD, and decreased FMD over
      time, would predict cIMT. DESIGN AND METHODS: FMD and cIMT were assessed using
      high-resolution Doppler ultrasound in 53 children (18 boys) aged 10.3 +/- 0.3
      years. FMD was assessed at baseline and 4-month and 30-month follow up. cIMT was
      assessed at 30-months. RESULTS: There was no significant relationship between FMD
      measured at baseline (10.7 +/- 4.3) and cIMT at 30 months. FMD was depressed at 4
      months (7.2 +/- 3.5, p < 0.05) and 30 months (8.2 +/- 3.3, p = 0.51). However,
      there was no correlation between changes in FMD and cIMT. CONCLUSION: Changes in
      arterial function occurred in young subjects across a 30-month time frame;
      however, these changes were unrelated to individual differences in cIMT in this
      cohort. These data contrast with findings in adults and indicate that longer
      periods of functional impairment may be necessary before atherosclerotic wall
      thickening becomes apparent in young people, suggesting there is a 'window of
      opportunity' for preventative intervention strategies.

PMID- 22584636
TI  - Effect of skilled and unskilled training on nerve regeneration and functional
      recovery.
AB  - The most disabling aspect of human peripheral nerve injuries, the majority of
      which affect the upper limbs, is the loss of skilled hand movements. Activity
      induced morphological and electrophysiological remodeling of the neuromuscular
      junction has been shown to influence nerve repair and functional recovery. In the
      current study, we determined the effects of two different treatments on the
      functional and morphological recovery after median and ulnar nerve injury. Adult
      Wistar male rats weighing 280 to 330 g at the time of surgery (N = 8-10
      animals/group) were submitted to nerve crush and 1 week later began a 3-week
      course of motor rehabilitation involving either "skilled" (reaching for small
      food pellets) or "unskilled" (walking on a motorized treadmill) training. During
      this period, functional recovery was monitored weekly using staircase and
      cylinder tests. Histological and morphometric nerve analyses were used to assess
      nerve regeneration at the end of treatment. The functional evaluation
      demonstrated benefits of both tasks, but found no difference between them (P >
      0.05). The unskilled training, however, induced a greater degree of nerve
      regeneration as evidenced by histological measurement (P < 0.05). These data
      provide evidence that both of the forelimb training tasks used in this study can
      accelerate functional recovery following brachial plexus injury.

PMID- 22584637
TI  - Prostate-specific membrane antigen can promote in vivo osseous metastasis of
      prostate cancer cells in mice.
AB  - Reports remain insufficient on whether and how prostate-specific membrane antigen
      (PSMA) can influence in vivo osseous metastasis of prostate cancer (PCa). In the
      present study, the authors induced stable expression of PSMA in mouse PCa cell
      line RM-1. In vivo osseous metastasis was induced in 37 6-week-old female C57BL/6
      mice weighing 22.45 +/- 0.456 g. RM-1 cells were actively injected into the
      femoral bone cavity, leading to bilateral dissymmetry of bone density in the
      femoral bone. Tumor cells were also detected in bone tissue by pathological
      examination. The impact on bone density was demonstrated by the significant
      difference between animals injected with RM-PSMA cells (0.0738 +/- 0.0185 g/cm2)
      and animals injected with RM-empty plasmid cells (0.0895 +/- 0.0241 g/cm2). The
      lytic bone lesion of the RM-PSMA group (68.4%) was higher than that of the
      control group (27.8%). Immunohistochemistry showed that the expression of both
      vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9)
      was distinctly higher in the RM-PSMA group than in the control group, while ELISA
      and Western blot assay indicated that VEGF and MMP-9 were higher in the RM-PSMA
      group compared to the control group (in vitro). Thus, the present study proposed
      and then confirmed for the first time that PSMA can promote in vivo osseous
      metastasis of PCa by increasing sclerotic destruction of PCa cells. Further
      analyses also suggested that PSMA functions positively on the invasive ability of
      RM-1 by increasing the expression of MMP-9 and VEGF by osseous metastases in
      vivo.

PMID- 22584638
TI  - Comparison of the variability of the onset and recovery from neuromuscular
      blockade with cisatracurium versus rocuronium in elderly patients under total
      intravenous anesthesia.
AB  - This study was designed to compare the variability of the onset and offset of the
      effect of two neuromuscular blocking drugs with different elimination pathways in
      adult and elderly patients during total intravenous anesthesia (TIVA). After
      Ethics Committee approval and patients' informed consent, the drugs were compared
      in 40 adult and 40 elderly patients scheduled for elective surgery under TIVA
      with tracheal intubation who were randomized to receive a single bolus dose of
      0.15 mg/kg cisatracurium or 0.9 mg/kg rocuronium. The time of onset of maximum
      depression, duration of action, and recovery index time were measured and
      recorded for each patient and variability is reported as means +/- standard
      deviation. Time of onset was significantly shorter for rocuronium than
      cisatracurium for the adult and elderly groups (P = 0.000), but the variability
      of cisatracurium was significantly greater compared with rocuronium for the same
      age groups (93.25 vs 37.01 s in the adult group and 64.56 vs 33.75 s in the
      elderly group; P = 0.000). The duration of the effect in the elderly group
      receiving rocuronium was significantly longer than in the elderly group receiving
      cisatracurium, and the variability of the duration was significantly greater in
      the rocuronium group than in the cisatracurium group. Mean time of recovery was
      significantly longer for the elderly group receiving rocuronium than for the
      elderly group receiving cisatracurium (P = 0.022), and variability was also
      greater (P = 0.002). Both drugs favored good intubating conditions. In
      conclusion, cisatracurium showed less variability in these parameters than
      rocuronium, especially in the elderly, a fact that may be of particular clinical
      interest.

PMID- 22584639
TI  - Association of Bartonella spp bacteremia with Chagas cardiomyopathy, endocarditis
      and arrhythmias in patients from South America.
AB  - Infection with Bartonella spp may cause cardiac arrhythmias, myocarditis and
      endocarditis in humans. The aim of the present study was to evaluate a possible
      association between Bartonella spp bacteremia and endocarditis, arrhythmia and
      Chagas cardiomyopathy in patients from Brazil and Argentina. We screened for the
      presence of bacterial 16S rRNA in human blood by PCR using oligonucleotides to
      amplify a 185-bp bacterial DNA fragment. Blood samples were taken from four
      groups of subjects in Brazil and Argentina: i) control patients without clinical
      disease, ii) patients with negative blood-culture endocarditis, iii) patients
      with arrhythmias, and iv) patients with chronic Chagas cardiomyopathy. PCR
      products were analyzed on 1.5% agarose gel to visualize the 185-bp fragment and
      then sequenced to confirm the identity of DNA. Sixty of 148 patients (40.5%) with
      cardiac disease and 1 of 56 subjects (1.8%) from the control group presented
      positive PCR amplification for Bartonella spp, suggesting a positive association
      of the bacteria with these diseases. Separate analysis of the four groups showed
      that the risk of a Brazilian patient with endocarditis being infected with
      Bartonella was 22 times higher than in the controls. In arrhythmic patients, the
      prevalence of infection was 45 times higher when compared to the same controls
      and 40 times higher for patients with Chagas cardiomyopathy. To the best of our
      knowledge this is the first report of the association between Bartonella spp
      bacteremia and Chagas disease. The present data may be useful for epidemiological
      and prevention studies in Brazil and Argentina.

PMID- 22584640
TI  - Prevalence of ERalpha-397 PvuII C/T, ERalpha-351 XbaI A/G and PGR PROGINS
      polymorphisms in Brazilian breast cancer-unaffected women.
AB  - Polymorphisms of hormone receptor genes have been linked to modifications in
      reproductive factors and to an increased risk of breast cancer (BC). In the
      present study, we have determined the allelic and genotypic frequencies of the
      ERalpha-397 PvuII C/T, ERalpha-351 XbaI A/G and PGR PROGINS polymorphisms and
      investigated their relationship with mammographic density, body mass index (BMI)
      and other risk factors for BC. A consecutive and unselected sample of 750
      Brazilian BC-unaffected women enrolled in a mammography screening program was
      recruited. The distribution of PGR PROGINS genotypic frequencies was 72.5, 25.5
      and 2.0% for A1A1, A1A2 and A2A2, respectively, which was equivalent to that
      encountered in other studies with healthy women. The distribution of ERalpha
      genotypes was: ERalpha-397 PvuII C/T: 32.3% TT, 47.5% TC, and 20.2% CC; ERalpha
      351 XbaI A/G: 46.3% AA, 41.7% AG and 12.0% GG. ERalpha haplotypes were 53.5% PX,
      14.3% Px, 0.3% pX, and 32.0% px. These were significantly different from most
      previously published reports worldwide (P < 0.05). Overall, the PGR PROGINS
      genotypes A2A2 and A1A2 were associated with fatty and moderately fatty breast
      tissue. The same genotypes were also associated with a high BMI in postmenopausal
      women. In addition, the ERalpha-351 XbaI GG genotype was associated with menarche
      >= 12 years (P = 0.02). ERalpha and PGR polymorphisms have a phenotypic effect
      and may play an important role in BC risk determination. Finally, if confirmed in
      BC patients, these associations could have important implications for
      mammographic screening and strategies and may be helpful to identify women at
      higher risk for the disease.

PMID- 22584641
TI  - PPM1B and P-IKKbeta expression levels correlated inversely with rat gastrocnemius
      atrophy after denervation.
AB  - Activated inhibitor of nuclear factor-kappaB kinase beta (IKKbeta) is necessary
      and sufficient for denervated skeletal muscle atrophy. Although several studies
      have shown that Mg(2+)/Mn(2+)-dependent protein phosphatase 1B (PPM1B)
      inactivated IKKbeta, few studies have investigated the role of PPM1B in
      denervated skeletal muscle. In this study, we aim to explore the expression and
      significance of PPM1B and phosphorylated IKKbeta (P-IKKbeta) during atrophy of
      the denervated gastrocnemius. Thirty young adult female Wistar rats were
      subjected to right sciatic nerve transection and were sacrificed at 0 (control),
      2, 7, 14, and 28 days after denervation surgery. The gastrocnemius was removed
      from both the denervated and the contralateral limb. The muscle wet weight ratio
      was calculated as the ratio of the wet weight of the denervated gastrocnemius to
      that of the contralateral gastrocnemius. RT-PCR and Western blot analysis showed
      that mRNA and protein levels of PPM1B were significantly lower than those of the
      control group at different times after the initiation of denervation, while P
      IKKbeta showed the opposite trends. PPM1B protein expression persistently
      decreased while P-IKKbeta expression persistently increased for 28 days after
      denervation. PPM1B expression correlated negatively with P-IKKbeta expression by
      the Spearman test, whereas decreasing PPM1B expression correlated positively with
      the muscle wet weight ratio. The expression levels of PPM1B and P-IKKbeta were
      closely associated with atrophy in skeletal denervated muscle. These results
      suggest that PPM1B and P-IKKbeta could be markers in skeletal muscle atrophy.

PMID- 22584642
TI  - Evaluation of renal function in sickle cell disease patients in Brazil.
AB  - The objective of this study was to investigate renal function in a cohort of 98
      patients with sickle cell disease (SCD) followed up at a tertiary hospital in
      Brazil. Clinical and laboratory characteristics at the time of the most recent
      medical examination were analyzed. Renal function was evaluated by the estimation
      of glomerular filtration rate (GFR) by the criteria of the Chronic Kidney Disease
      Epidemiology Collaboration (CKD-EPI). We compared patients with normal GFR to
      patients with decreased GFR (<60 mL.min(-1).(1.73 m(2))(-1)) and hyperfiltration
      (>120 mL.min(-1).(1.73 m(2))(-1)). Comparison between patients according to the
      use of hydroxyurea and comparison of clinical and laboratory parameters according
      to GFR were also carried out. Average patient age was 33.8 +/- 13.3 years (range
      19-67 years), and 57 (58.1%) patients were females. The comparison of patients
      according to GFR showed that patients with decreased GFR (<60 mL.min(-1).(1.73
      m(2))(-1)) were older, had lower levels of hematocrit, hemoglobin and platelets
      and higher levels of urea and creatinine. Independent risk factors for decreased
      GFR were advanced age (OR = 21.6, P < 0.0001) and anemia (OR = 39.6, P < 0.0001).
      Patients with glomerular hyperfiltration tended to be younger, had higher levels
      of hematocrit, hemoglobin and platelets and lower levels of urea and creatinine,
      with less frequent urinary abnormalities. Hydroxyurea, at the dosage of 500-1000
      mg/day, was being administered to 28.5% of the patients, and there was no
      significant difference regarding renal function between the two groups. Further
      studies are required to establish the best therapeutic approach to renal
      abnormalities in SCD.

PMID- 22584643
TI  - Short-term levosimendan treatment protects rat testes against oxidative stress.
AB  - The objective of this study was to evaluate the effect of short-term levosimendan
      exposure on oxidant/antioxidant status and trace element levels in the testes of
      rats under physiological conditions. Twenty male Wistar albino rats were randomly
      divided into two groups of 10 animals each. Group 1 was not exposed to
      levosimendan and served as control. Levosimendan (12 ug/kg) diluted in 10 mL 0.9%
      NaCl was administered intraperitoneally to group 2. Animals of both groups were
      sacrificed after 3 days and their testes were harvested for the determination of
      changes in tissue oxidant/antioxidant status and trace element levels. Tissue
      malondialdehyde (MDA) was significantly lower in the levosimendan group (P <
      0.001) than in the untreated control group and superoxide dismutase and
      glutathione peroxidase (GSH-Px) levels were significantly higher in the
      levosimendan group (P < 0.001). Carbonic anhydrase, catalase and GSH levels were
      not significantly different from controls. Mg and Zn levels of testes were
      significantly higher (P < 0.001) and Co, Pb, Cd, Mn, and Cu were significantly
      lower (P < 0.001) in group 2 compared to group 1. Fe levels were similar for the
      two groups (P = 0.94). These results suggest that 3-day exposure to levosimendan
      induced a significant decrease in tissue MDA level, which is a lipid peroxidation
      product and an indicator of oxidative stress, and a significant increase in the
      activity of an important number of the enzymes that protect against oxidative
      stress in rat testes.

PMID- 22584644
TI  - Hemodynamic mechanisms of the attenuated blood pressure response to mental stress
      after a single bout of maximal dynamic exercise in healthy subjects.
AB  - To determine the hemodynamic mechanisms responsible for the attenuated blood
      pressure response to mental stress after exercise, 26 healthy sedentary
      individuals (age 29 +/- 8 years) underwent the Stroop color-word test before and
      60 min after a bout of maximal dynamic exercise on a treadmill. A subgroup (N =
      11) underwent a time-control experiment without exercise. Blood pressure was
      continuously and noninvasively recorded by infrared finger photoplethysmography.
      Stroke volume was derived from pressure signals, and cardiac output and
      peripheral vascular resistance were calculated. Perceived mental stress scores
      were comparable between mental stress tests both in the exercise (P = 0.96) and
      control (P = 0.24) experiments. After exercise, the blood pressure response to
      mental stress was attenuated (pre: 10 +/- 13 vs post: 6 +/- 7 mmHg; P < 0.01)
      along with lower values of systolic blood pressure (pre: 129 +/- 3 vs post: 125
      +/- 3 mmHg; P < 0.05), stroke volume (pre: 89.4 +/- 3.5 vs post: 76.8 +/- 3.8 mL;
      P < 0.05), and cardiac output (pre: 7.00 +/- 0.30 vs post: 6.51 +/- 0.36 L/min; P
      < 0.05). Except for heart rate, the hemodynamic responses and the mean values
      during the two mental stress tests in the control experiment were similar (P >
      0.05). In conclusion, a single bout of maximal dynamic exercise attenuates the
      blood pressure response to mental stress in healthy subjects, along with lower
      stroke volume and cardiac output, denoting an acute modulatory action of exercise
      on the central hemodynamic response to mental stress.

PMID- 22584646
TI  - Cloning, bioinformatics analysis, and expression of the dust mite allergen Der f
      5 of Dermatophagoides farinae.
AB  - Crude extracts of house dust mites are used clinically for diagnosis and
      immunotherapy of allergic diseases, including bronchial asthma, perennial
      rhinitis, and atopic dermatitis. However, crude extracts are complexes with non
      allergenic antigens and lack effective concentrations of important allergens,
      resulting in several side effects. Dermatophagoides farinae (Hughes; Acari:
      Pyroglyphidae) is one of the predominant sources of dust mite allergens, which
      has more than 30 groups of allergen. The cDNA coding for the group 5 allergen of
      D. farinae from China was cloned, sequenced and expressed. According to alignment
      using the VECTOR NTI 9.0 software, there were eight mismatched nucleotides in
      five cDNA clones resulting in seven incompatible amino acid residues, suggesting
      that the Der f 5 allergen might have sequence polymorphism. Bioinformatics
      analysis revealed that the matured Der f 5 allergen has a molecular mass of
      13604.03 Da, a theoretical pI of 5.43 and is probably hydrophobic and
      cytoplasmic. Similarities in amino acid sequences between Der f 5 and allergens
      of other domestic mite species, viz. Der p 5, Blo t 5, Sui m 5, and Lep d 5, were
      79, 48, 53, and 37%, respectively. Phylogenetic analysis indicated that Der f 5
      and Der p 5 clustered together. Blo t 5 and Ale o 5 also clustered together,
      although Blomia tropicalis and Aleuroglyphus ovatus belong to different mite
      families, viz. Echimyopodidae and Acaridae, respectively.

PMID- 22584645
TI  - 2-Bromo-1,4-naphthoquinone: a potentially improved substitute of menadione in
      ApatoneTM therapy.
AB  - ApatoneTM, a combination of menadione (2-methyl-1,4-naphthoquinone, VK3) and
      ascorbic acid (vitamin C, VC) is a new strategy for cancer treatment. Part of its
      effect on tumor cells is related to the cellular pro-oxidative imbalance provoked
      by the generation of hydrogen peroxide (H2O2) through naphthoquinone redox
      cycling. In this study, we attempted to find new naphthoquinone derivatives that
      would increase the efficiency of H2O2 production, thereby potentially increasing
      its efficacy for cancer treatment. The presence of an electron-withdrawing group
      in the naphthoquinone moiety had a direct effect on the efficiency of H2O2
      production. The compound 2-bromo-1,4-naphthoquinone (BrQ), in which the bromine
      atom substituted the methyl group in VK3, was approximately 10- and 19-fold more
      efficient than VK3 in terms of oxygen consumption and H2O2 production,
      respectively. The ratio [H2O2]produced / [naphthoquinone]consumed was 68 +/- 11
      and 5.8 +/- 0.2 (uM/uM) for BrQ and VK3, respectively, indicating a higher
      efficacy of BrQ as a catalyst for the autoxidation of ascorbic acid. Both VK3 and
      BrQ reacted with glutathione (GSH), but BrQ was the more effective substrate.
      Part of GSH was incorporated into the naphthoquinone, producing a nucleophilic
      substitution product (Q-SG). The depletion of BrQ by GSH did not prevent its
      redox capacity since Q-SG was also able to catalyze the production of reactive
      oxygen species. VK3/VC has already been submitted to clinical trials for the
      treatment of prostate cancer and has demonstrated promising results. However,
      replacement of VK3 with BrQ will open new lines of investigation regarding this
      approach to cancer treatment.

PMID- 22584647
TI  - The cost-effectiveness of primary prophylactic implantable defibrillator therapy
      in patients with ischaemic or non-ischaemic heart disease: a European analysis.
AB  - AIMS: It remains unclear whether primary prophylactic implantable cardioverter
      defibrillator (ICD) therapy is cost-effective compared with a 'no ICD strategy'
      in the European health care setting. We performed a cost-effectiveness analysis
      for a cohort of patients with a left ventricular ejection fraction <40% and
      ischaemic or non-ischaemic heart disease. METHODS AND RESULTS: A Markov decision
      analytic model was used to evaluate long-term survival, quality-adjusted life
      years (QALYs), and lifetime costs for a cohort of patients with a reduced left
      ventricular function without previous arrhythmias, managed with a prophylactic
      ICD. Input data on effectiveness were derived from a meta-analysis of primary
      prophylactic ICD-only therapy randomized trials, from a prospective cohort study
      of ICD patients, from a health care utilization survey, and from the literature.
      Input data on costs were derived from a micro-cost analysis. Data on quality-of
      life were derived from the literature. Deterministic and probabilistic
      sensitivity analysis was performed to assess the uncertainty. Probabilistic
      sensitivity analysis demonstrated a mean lifetime cost of ?50 685 +/- ?4604 and
      6.26 +/- 0.64 QALYs for patients in the 'no ICD strategy'. Patients in the 'ICD
      strategy' accumulated ?86 759 +/- ?3343 and an effectiveness of 7.08 +/- 0.71
      QALYs yielding an incremental cost-effectiveness ratio of ?43 993/QALY gained
      compared with the 'no ICD strategy'. The probability that ICD therapy is cost
      effective was 65% at a willingness-to-pay threshold of ?80 000/QALY. CONCLUSION:
      Our results suggest that primary prophylactic ICD therapy in patients with a left
      ventricular ejection fraction <40% and ischaemic or non-ischaemic heart disease
      is cost-effective in the European setting.

PMID- 22584650
TI  - Shift working: safety or savings?

PMID- 22584648
TI  - Influence of baseline left ventricular function on the clinical outcome of
      surgical ventricular reconstruction in patients with ischaemic cardiomyopathy.
AB  - AIMS: The Surgical Treatment for Ischemic Heart Failure (STICH) trial
      demonstrated no overall benefit when surgical ventricular reconstruction (SVR)
      was added to coronary artery bypass grafting (CABG) in patients with ischaemic
      cardiomyopathy. The present analysis was to determine whether, based on baseline
      left ventricular (LV) function parameters, any subgroups could be identified that
      benefited from SVR. METHODS AND RESULTS: Among the 1000 patients enrolled, Core
      Lab measures of baseline LV function with adequate quality were obtained in 710
      patients using echocardiography, in 352 using cardiovascular magnetic resonance,
      and in 344 using radionuclide imaging. The relationship between LV end-systolic
      volume index (ESVI), end-diastolic volume index, ejection fraction (EF), regional
      wall motion abnormalities, and outcome were first assessed only by
      echocardiographic measures, and then by 13 algorithms using a different hierarchy
      of imaging modalities and their quality. The median ESVI and EF were 78.0 (range:
      22.8-283.8) mL/m2 and 28.0%, respectively. Hazard ratios comparing the randomized
      arms by subgroups of LVESVI and LVEF measured by echocardiography found that
      patients with smaller ventricles (LVESVI <60 mL/m2) and better LVEF (>=33%) may
      have benefitted by SVR, while those with larger ventricles (LVESVI >90 mL/m(2))
      and lower LVEF (<=25%) did worse with SVR. Algorithms using all three imaging
      modalities found a weaker relationship between LV global function and the effects
      of SVR. The extent of regional wall motion abnormality did not influence the
      effects of SVR. CONCLUSIONS: Subgroup analyses of the STICH trial suggest that
      patients with less dilated LV and better LVEF may benefit from SVR, while those
      with larger LV and poorer LVEF may do worse. Clinical Trial Registration #:
      NCT00023595.

PMID- 22584651
TI  - How can we maximize the use of compression hosiery?

PMID- 22584649
TI  - Ethylmalonic encephalopathy associated with crescentic glomerulonephritis.
AB  - Ethylmalonic encephalopathy (EE) is a rare autosomal recessive disorder caused by
      mutations in the ETHE1 gene and characterized by chronic diarrhea,
      encephalopathy, relapsing petechiae and acrocyanosis. Nephrotic syndrome has been
      described in an infant with EE but the renal histology findings were not
      described in previous reports. We report a Palestinian girl with EE who presented
      with chronic diarrhea, encephalopathy, petechial rash and acrocyanosis.
      Subsequently, she developed progressive deterioration of renal function caused by
      rapidly progressive glomerulonephritis resulting in death within few days. This
      is, to our knowledge, the first reported occurrence of rapidly progressive
      glomerulonephritis in a child with ethylmalonic encephalopathy. Its presence is a
      serious complication associated with poor prognosis and may be explained by the
      diffuse vascular damage.

PMID- 22584652
TI  - Pin site infection in orthopaedic external fixation devices.
AB  - External fixation is a well-established mode of treatment within orthopaedics;
      however, despite continued research, pin site infection is still a problem. Pin
      site infection may cause pain and discomfort to the patient, and result in
      osteomyelitis or sepsis if minor infection is not managed in a timely and
      appropriate manner. Fundamental issues such as the assessment and reporting of
      infection are important in dealing with pin site infection, as is the ongoing
      management of the pin site itself. Many types of care are evident, with varying
      evidence to support their use in clinical practice. This article will discuss the
      identification and classification of pin site infection and the methods of care.

PMID- 22584653
TI  - Mattress cleanliness: the role of monitoring and maintenance.
AB  - A clean and tidy environment provides the right setting for good patient care. It
      is fundamental in preventing and/or controlling the spread of healthcare
      associated infections (HCAI). Cleanliness is an essential component for the
      comfort and dignity of patients, particularly those for whom a hospital is home
      for any length of time. Patients spend a lot of their time in bed so it is
      important for them to be provided with well maintained and clean mattresses.
      Beds, and especially the mattresses, should be cleaned and inspected regularly so
      patients know they are being cared for in a clean and safe environment. To
      prolong the life of the mattress and reduce infection risks, inspections for
      damage and contamination must take place on a regular basis. Assessment criteria
      for the audit of a mattress can include a visual inspection, a cover permeability
      test and a foam support surface test. These assessments will ensure the mattress
      is compliant with current standards and identify whether or not they require
      condemning. Mattress care can be improved by adopting unified good practices that
      can be standardized and audited regularly.

PMID- 22584654
TI  - Blood culture collection: quality assurance for ANTT.

PMID- 22584655
TI  - Exploring compassion: implications for contemporary nursing. Part 1.
AB  - The origin of compassion is firmly rooted in religious ideologies. In 19th
      century Great Britain, Christianity was the prominent religion and scripture
      advocated that followers should always be compassionate in their deeds and
      actions. Florence Nightingale was a Christian and translated her ideals into the
      characterization of the professional nurse. The image of the ministering angel,
      performing the work of God, was perpetuated for some time. However, as the
      profession of nursing advanced to develop evidence-based practice, some of the
      ethos of the compassionate nursing character was seemingly lost in favour of
      technical skills. This is supported by evidence suggesting that nurses have a
      decreased affinity with the ethos of altruism. Recent reports have highlighted
      negative patient experiences which reflect a clear lack of compassionate nursing
      care. This has led to a variety of documents re-endorsing the concept of
      compassion as a core and fundamental nursing value. This has raised several
      issues for nursing practice which require due consideration if the profession is
      to restore the image of the compassionate nurse, technically skilled and
      clinically effective, equipped with the appropriate skills, knowledge, values and
      attitudes to fulfil the pledges to respond to patients with humanity and kindness
      and to deliver high-quality compassionate care.

PMID- 22584656
TI  - Moving and handling and patient safety: analysis of clinical incidents.
AB  - AIM: The aim of this study is to identify the potential contribution of moving
      and handling practice to clinical incidents through an analysis of incident data.
      BACKGROUND: Previous studies focusing on moving and handling have highlighted
      potential harm to patients through poor practice, and have suggested that this
      might be an issue for patient safety. However, this has not been identified in
      studies analysing clinical incident reports, where the potential contribution of
      moving and handling has not been recognized. This study reports an analysis of
      clinical incident data from the specific perspective of moving and handling.
      DESIGN: Survey of clinical incident reports in hospital in-patient care settings
      Method: A random sample of 500 incident reports was analysed using descriptive
      statistics and thematic analysis of qualitative data. RESULTS: There is an
      indication that some staff are not following recommended moving and handling
      policy through a lack of risk assessment; for example, in the selection of
      appropriate actions to assist patients, and in the prevention of further
      occurrences of incidents where patients had fallen. The limited detail within the
      reports affected consideration of the causes of the incidents and actions that
      could be taken to prevent a further occurrence. CONCLUSIONS: Some of the reported
      staff actions may contravene policy guidelines. Missing detail in the incident
      reports inhibited investigation of incidents that could lead to appropriate and
      safe systems of work being identified.

PMID- 22584657
TI  - How to survive writing assignments.

PMID- 22584658
TI  - Health and medical services for the 2012 Olympic Games.

PMID- 22584659
TI  - Intellectual disability nursing and transcultural care.
AB  - In today's healthcare environment, nurses are urged to use up-to-date research
      evidence to ensure better patient outcomes and inform nursing decisions, actions
      and interactions with patients. Within the practice setting, there is an
      increasing challenge to provide care to patients from minority ethnic groups. In
      order to deliver care to different cultural groups, nurses need to recognize and
      empathize with patients' belief systems, being mindful of their diverse cultural
      needs. This article presents the concept of transcultural care and identifies
      issues within intellectual disability nursing through a focus on the components
      identified by Campinha-Bacote (2002; 2003) and Cortis (2003): cultural awareness,
      cultural skill, cultural knowledge, cultural encounter and cultural desire. It
      highlights the issues which are relevant to nursing practice, cultural care and
      service provision for persons with intellectual disability from ethnic minorities
      in Ireland.

PMID- 22584660
TI  - Implementation of nursing grand rounds at a large acute hospital trust.
AB  - This article outlines the implementation of nursing grand rounds (NGRs) in one of
      the largest NHS teaching hospitals in the UK, to share clinical and professional
      expertise in providing quality and evidence-based care to registered nurses and
      allied health professionals. A pilot was successfully trialled on one hospital
      site for 3 months, which was then rolled out across the organization. The
      objectives of the programme encouraged participation from clinical nurse
      specialist colleagues to promote their role and present their work, including
      evidenced-based care, service improvement and research. A variety of
      multidisciplinary team members attended and highly evaluated the 3-month pilot
      NGRs. The criticism of having an inappropriately sized venue was addressed, and
      this coupled with offering food before lectures has encouraged greater
      participation and networking.

PMID- 22584661
TI  - Patient satisfaction in three clinics managing long-term conditions.
AB  - People with long-term conditions are frequent visitors to outpatient clinics. In
      order that they get the best out of their visits, the health professionals taking
      care of them need to understand their experiences and work towards service
      improvements. A survey of 3 clinics (HIV, rheumatology, diabetes) was undertaken
      using a set of three simple, open questions. A total of 147 people responded
      that, above all, care, attention, friendliness and efficiency were their most
      valued experiences. Shorter waiting times and cheaper car parking came up most
      frequently as sources of dissatisfaction. The study concludes that there were no
      distinct differences in the experiences of the patients in each clinic. All care
      needs were relatively simple and, on the whole, met.

PMID- 22584662
TI  - Regulating cosmetic surgery: a scalpel where it is needed.
AB  - This paper considers the recent controversies around the regulation of cosmetic
      surgery procedures. The author suggests that any review considering reform of the
      law in this area should not only look at issues concerning the safety of the
      procedures and competence of the practitioners, but should also address the
      question of which procedures should be allowed. In particular, the author
      advocates that there should be a review as to the whether cosmetic procedures
      should be made available to those under the age of 18 years. The paper also
      discusses analogous legislation in Queensland, Australia and explores whether
      this could be a useful model for legislative reform.

PMID- 22584663
TI  - Re-profiling the nursing profession through undergraduate education.

PMID- 22584664
TI  - Professional development: from staff nurse to nurse consultant. Part 5: degrees
      and your worth.

PMID- 22584665
TI  - Developing the NHS workforce of the future.

PMID- 22584666
TI  - Recent healthcare reports reveal patient safety failings.

PMID- 22584667
TI  - Collectively tackling student attrition.

PMID- 22584668
TI  - Comparison of uranyl extraction mechanisms in an ionic liquid by use of
      malonamide or malonamide-functionalized ionic liquid.
AB  - The extraction of uranyl from acidic (HNO(3)) aqueous solutions toward an ionic
      liquid phase, C(1)-C(4)-imTf(2)N (1-methyl,3-butylimidazolium Tf(2)N), has been
      investigated as a function of initial acid concentration and ligand concentration
      for two different extracting moieties: a classical malonamide, N,N'-dimethyl-N,N'
      dibutylmalonamide (DMDBMA) and a functionalized IL composed of the Tf(2)N(-)
      anion and an imidazolium cation on which a malonamide pattern has been grafted
      (FIL-MA). The extraction mechanism, as demonstrated through the influence of
      added C(1)-C(4)-imCl or added LiTf(2)N in the aqueous phase, is slightly
      different between the DMDBMA and FIL-MA extracting agents. Modeling of the
      extraction data evidences a double extraction mechanism, with cation exchange of
      UO(2)(2+)versus 2 H(+) for DMDBMA or versus C(1)-C(4) -im(+) and H(+) for FIL-MA
      at low acidic values, and through anion exchange of [UO(2)(NO(3))(3)](-)versus
      Tf(2)N(-) for both ligands at high HNO(3) concentrations. The FIL-MA molecule is
      more efficient than its classical DMDBMA parent.

PMID- 22584669
TI  - Cytokines induce tight junction disassembly in airway cells via an EGFR-dependent
      MAPK/ERK1/2-pathway.
AB  - Epithelial barrier permeability is altered in inflammatory respiratory disorders
      by a variety of noxious agents through modifications of the epithelial cell
      structure that possibly involve tight junction (TJ) organization. To evaluate in
      vitro whether pro-inflammatory cytokines involved in the pathogenesis of
      respiratory disorders could alter TJ organization and epithelial barrier
      integrity, and to characterize the signal transduction pathway involved Calu-3
      airway epithelial cells were exposed to TNF-a, IL-4 and IFN-g to assess changes
      in: (a) TJ assembly, that is, occludin and zonula occludens (ZO)-1 expression and
      localization, evaluated by confocal microscopy; (b) apoptotic activity,
      quantified using terminal transferase deoxyuridine triphosphate nick-end labeling
      staining; (c) epithelial barrier integrity, detected as transmembrane electrical
      resistance and expressed as G(T) values; (d) epidermal growth factor receptor
      (EGFR)-dependent mitogenactivated protein (MAP) kinase (MAPK)/extracellular
      signal-regulated kinases (ERK)1/2 phosphorylation, assessed by western blotting.
      Exposure to cytokines for 48 h induced a noticeable downregulation of the TJ
      transmembrane proteins. The degree ZO-1 and occludin colocalization was 62+/-2%
      in control cultures and significantly decreased in the presence of TNF-a (47+/
      3%), IL-4 (43+/-1%) and INF-g (35+/-3%). Although no apoptosis induction was
      detected following exposure to cytokines, changes in the epithelial barrier
      integrity were observed, with a significant enhancement in paracellular
      conductance. G(T) values were, respectively, 1.030+/-0.0, 1.300+/-0.04, 1.260+/
      0.020 and 2.220+/-0.015 (mS/cm2)1000 in control cultures and in those exposed to
      TNF-a, IFN-g and IL-4. The involvement of EGFR-dependent MAPK/ERK1/2 signaling
      pathway in cytokine-induced damage was demonstrated by a significant increase in
      threonine/tyrosine phosphorylation of ERK1/2, already detectable after 5 min
      incubation. All these cytokine-induced changes were markedly prevented when Calu
      3 cells were cultured in the presence of an EGFR inhibitor (AG1478, 1 MUM) or a
      MAP kinase inhibitor (U0126, 25 MUM). In conclusion, cytokine-induced epithelial
      injury includes TJ disassembly and epithelial barrier permeability alteration and
      involves the EGFR-dependent MAPK/ERK1/2 signaling pathway.

PMID- 22584670
TI  - An inhibitor of transforming growth factor beta type I receptor ameliorates
      muscle atrophy in a mouse model of caveolin 3-deficient muscular dystrophy.
AB  - Skeletal muscle expressing Pro104Leu mutant caveolin 3 (CAV3(P104L)) in mouse
      becomes atrophied and serves as a model of autosomal dominant limb-girdle
      muscular dystrophy 1C. We previously found that caveolin 3-deficient muscles
      showed activated intramuscular transforming growth factor beta (TGF-beta)
      signals. However, the cellular mechanism by which loss of caveolin 3 leads to
      muscle atrophy is unknown. Recently, several small-molecule inhibitors of TGF
      beta type I receptor (TbetaRI) kinase have been developed as molecular-targeting
      drugs for cancer therapy by suppressing intracellular TGF-beta1, -beta2, and 
      beta3 signaling. Here, we show that a TbetaRI kinase inhibitor, Ki26894, restores
      impaired myoblast differentiation in vitro caused by activin, myostatin, and TGF
      beta1, as well as CAV3(P104L). Oral administration of Ki26894 increased muscle
      mass and strength in vivo in wild-type mice, and improved muscle atrophy and
      weakness in the CAV3(P104L) mice. The inhibitor restored the number of satellite
      cells, the resident stem cells of adult skeletal muscle, with suppression of the
      increased phosphorylation of Smad2, an effector, and the upregulation of p21
      (also known as Cdkn1a), a target gene of the TGF-beta family members in muscle.
      These data indicate that both TGF-beta-dependent reduction in satellite cells and
      impairment of myoblast differentiation contribute to the cellular mechanism
      underlying caveolin 3-deficient muscle atrophy. TbetaRI kinase inhibitors could
      antagonize the activation of intramuscular anti-myogenic TGF-beta signals,
      thereby providing a novel therapeutic rationale for the alternative use of this
      type of anticancer drug in reversing muscle atrophy in various clinical settings.

PMID- 22584671
TI  - Busulfan-mediated germ cell depletion does not alter gonad differentiation in the
      urodele amphibian Pleurodeles waltl.
AB  - It is not known in urodele amphibians whether germ cells (GCs) are indispensable
      for gonadal differentiation. In order to address this question in the newt
      Pleurodeles waltl, we first cloned the ortholog of VASA which is known as a GC
      marker in many species. Male (ZZ) and female (ZW) larvae were then exposed to the
      alkylating agent busulfan (25 MUg/ml for 3 days) just after hatching (stage 36).
      In the main body of busulfan-treated larvae, PwVASA mRNA expression decreased
      before gonad differentiation in both sexes (at stage 50). This suggested GC
      depletion which was confirmed by histology, with a complete absence of GCs
      observed slightly earlier in females (stage 54) than in males (stage 54 + 60
      days). In busulfan-treated ZW larvae, the presence of the typical central cavity
      and expression of a high level of aromatase mRNA confirmed the ovarian phenotype.
      In busulfan-treated ZZ larvae, the presence of a medulla surrounded by a thin
      cortex and a low level of aromatase mRNA confirmed the testis phenotype. At the
      juvenile stage, efferent ducts and lobules were present in the first testis lobe.
      Taken together, these data suggest that GC depletion does not alter gonad
      differentiation in P. waltl.

PMID- 22584672
TI  - Realistic outcomes.
AB  - Patient-centred care is one of the new mantras of nursing and medicine. However,
      I wonder if this is a concept we are starting to take for granted, and if our
      understanding of it is based more on assumptions than we'd like to admit. I've
      often interpreted it as the need to involve patients in decision-making and
      ensure they are happy with the care they receive. In short, we want their
      involvement and, ultimately, stamp of approval.

PMID- 22584673
TI  - Comparison of the interface pressure and stiffness of four types of compression
      systems.
AB  - OBJECTIVE: To compare interface pressure (IP) and static stiffness index (SSI) of
      four different compression systems currently in use for the treatment of patients
      with venous leg ulcer. METHOD: Fifty-two ambulatory adults with healthy legs were
      recruited at random at a study centre after they had consented. The evaluated
      systems were: short-stretch system (SSB), Rosidal sys (Lohmann & Rauscher),
      multilayer bandaging (LSB) Profore (Smith & Nephew), Vari-stretch (VSB) ProGuide
      (Smith & Nephew) and tubular compression (CS) Rosidal Mobil (Lohmann & Rauscher).
      Interface pressure was measured using Kikuhime (Harada Corp.), placing a 3 cm
      diameter probe at the B1 point. IP recording took place in the supine and
      standing positions, while sitting and during walking, on application of the
      compression systems and every 15 minutes thereafter for 4 hours. RESULTS: The IPs
      of SSB, LSB and VSB, measured immediately after bandage application, were
      significantly higher than that of CS (all p < 0.05). During the 4-hour study
      period, the IP for both VSB and LSB measured in the supine position initially
      increased to > 60 mmHg. Their overall mean IPs in the supine position were 48.96
      +/- 3.99 mmHg and 48.12 +/- 4.57 mmHg, respectively. SSB and CS demonstrated more
      tolerable IP levels in this position of < 40 mmHg, which was similar to those
      when sitting. All systems maintained at least 40 mmHg in walking. SSB had a high
      SSI of 20 throughout the study. LSB followed with an SSI of 18 at the start,
      which reduced to 13, while the SSI for VSB decreased from 17 to 12 and CS, with
      an SSI of 6, lagged behind. CONCLUSION: These results may contribute to the
      understanding of IP and SSI of the four different compression systems evaluated.
      The IP and SSI data presented give clinicians an indication of the appropriate
      frequency of re-application of compression, and preliminary data on choosing a
      safe and effective compression treatment for their patients. DECLARATION OF
      INTEREST: The investigators received an educational grant from Lohmann & Rauscher
      GmbH & Co KG for this study.

PMID- 22584674
TI  - Use of specialist knowledge and experience to manage patients with mixed
      aetiology leg ulcers.
AB  - OBJECTIVE: To discuss the role of the clinical nurse specialist in managing
      patients with ulceration caused by mixed venous arterial disease. METHOD: A small
      scale retrospective audit study of eight mixed aetiology patients drawn from the
      caseload of leg ulcer patients within a specialist leg ulcer service in Ayrshire,
      Scotland was conducted by two specialist nurses with over 8 years' experience in
      specialist leg ulcer management. Patients were individually assessed using
      Doppler ultrasound and a rigorous set of validated risk factor criteria. Where
      Doppler ultrasound was considered to be unreliable, due to an inability to detect
      sounds, or where further diagnostic information was required in order to safely
      plan care, arterial duplex scanning was carried out by the cardiac department at
      Ayr Hospital. All patients were treated with a cohesive inelastic compression
      bandage system and closely observed by the specialist nurse. RESULTS: All eight
      patients with mixed aetiology leg ulcers were reported to experience complete
      ulcer healing within 6-30 weeks after first application of the inelastic bandage
      system. The regimen was well tolerated by all patients and no adverse events were
      recorded. CONCLUSION: With accurate assessment and treatment by a specialist
      team, patients with mixed venous arterial disease were safely and successfully
      managed where they may have remained unhealed. DECLARATION OF INTEREST: This was
      an independent retrospective audit study conducted by two clinical nurse
      specialists, with educational support by Activa Healthcare to assist in bringing
      it to print.

PMID- 22584675
TI  - Inaugural professorial lectures: tissue viability.
AB  - The Tissue Viability Practice Development Unit at Birmingham City University
      aspires to be a centre of excellence, making a real difference to patients, and
      the carers and professionals looking after them. March 14 marked the inaugural
      lectures of Professors Michael Clark, Jackie Stephen-Haynes and David Gray,
      sponsored by the JWC. Their involvement in what the TVPDU is trying to achieve is
      a fantastic opportunity, both for the unit itself and for the field of tissue
      viability as a whole.

PMID- 22584676
TI  - Disposable NPWT device to facilitate early patient discharge following complex
      DFU.
AB  - Negative pressure wound therapy (NPWT) is a valuable tool in complex wound
      management. Despite its popularity, NPWT therapy systems can have drawbacks,
      including reduced mobility and cost; therefore, NPWT is predominantly hospital
      based. The advent of a new, lightweight and disposable system may aid early
      discharge and permit outpatient treatment. This case report describes how one
      such system facilitated early discharge in a patient with a complex diabetic foot
      ulcer.

PMID- 22584677
TI  - The impact of water mattresses on incidence of PUs in patients with spinal cord
      injuries in Nigeria.
AB  - OBJECTIVE: To evaluate the impact of water mattresses on the incidence of
      pressure ulcers and length of hospitalisation in patients with spinal cord
      injuries in Nigeria. METHOD: A retrospective review was conducted of all patients
      who presented and were managed for complete traumatic spinal cord injury between
      January 2005 and December 2008. This period included 2 years prior to, and 2
      years following, the introduction of water mattresses to the ward; patients from
      these periods were grouped as A and B, respectively. Information collated from
      the medical records included demographic data, wound aetiology, time to
      presentation, level of injury, complications, treatment, and duration of
      hospitalisation and follow-up. Outcome measures were presence or absence of
      pressure ulcers and length of hospital stay. RESULTS: In total, 201 patients were
      treated within the study period. Of these, 99 patients met the inclusion
      criteria; 35 patients (19 paraplegics and 16 tetraplegics) were managed between
      2005 and 2006 (group A), while 64 patients (28 paraplegics and 36 tetraplegics)
      were managed in 2007 and 2008 (group B). The age range of the included patients
      was 9-76 years (39.0 +/- 4.6 years and 41.5 +/- 3.2 years for groups A and B,
      respectively) and all were male. Patient characteristics were similar for the two
      groups; however, there was a significant difference between the two groups in
      terms of presence of pressure ulcers, deteriorating of existing ulcers and
      condition of the patient on discharge (p < 0.05). CONCLUSION: The majority of
      pressure ulcers are preventable and a simple support surface, such as water
      mattresses, can reduce the incidence and magnitude of pressure ulceration, thus
      reducing hospital stay. DECLARATION OF INTEREST: The authors do not have any
      financial relationship with any organisation that manufactures water mattresses,
      either locally or overseas. There were no external sources of funding for this
      study.

PMID- 22584678
TI  - Amniotic membrane reduces wound size in early stages of the healing process.
AB  - OBJECTIVE: To investigate the effects of dispase de-epithelialised, glycerol
      cryopreserved amniotic membrane (AM) on full-thickness skin defects, using a rat
      model. METHOD: Skin defects of 15 mm diameter were surgically created and
      measured on the scalps of 53 male rats. Animals were divided into two groups and
      followed for 0, 3, 7, 14 or 21 days. AM group wounds were covered with de
      epithelialised AM and sodium chloride-moistened Aquacel (ConvaTec Inc.); control
      group wounds were covered with sodium chloride-moistened Aquacel alone. After the
      follow-up, wounds were measured again, serum samples were taken and wound sites
      were harvested for histological analysis. Systemic interleukin-4 (IL-4) levels
      were analysed from serum. RESULTS: On day 3, a statistically significant
      difference (p < 0.01) was observed in mean wound size, with wound size in the AM
      group smaller than in the control group (60 +/- 12% vs 81 +/- 13% of the original
      size); other time points showed no significance difference in wound size between
      the two groups. We could not detect differences between the groups in
      histological parameters or serum IL -4 levels. CONCLUSION: According to this
      study, AM enhances early stage wound healing in terms of wound size but its
      effect decreases in later phases. The IL-4 results provide no clear evidence that
      IL-4 contributes to the effect of AM on wound healing. DECLARATION OF INTEREST:
      This study was financially supported by the Competitive Research Funding of the
      Tampere University Hospital (Grant 9H041, 9J047). The authors have no additional
      conflicts of interest to declare.

PMID- 22584679
TI  - Response to White and Cutting critique.
AB  - Response to White and Cutting critique  In their letter, published in the March
      issue of JWC, White and Cutting raised concerns about clinical visualisation of
      wound biofilm in the absence of a definitive assay or validation of visual
      observations with microscopic confirmation. While I acknowledge that science
      plays a critical role in extending our knowledge of the role of biofilm in wound
      healing, clinicians cannot ignore patients' needs, or the patterns we observe as
      experts in our practice, while we await such scientific developments.

PMID- 22584680
TI  - Enhancing patient recovery following lower limb arthroplasty with a modern wound
      dressing: a prospective, comparative audit.
AB  - OBJECTIVE: To assess current wound care practice, implement a potentially
      improved regimen and re-evaluate practice. METHOD: Two prospective clinical
      audits were performed over a 6-month period, involving 100 patients undergoing
      hip or knee arthroplasty. Fifty consecutive patients with traditional dressings
      (Mepore; Molnlycke) were evaluated prior to a change in practice to a modern
      dressing (Aquacel Surgical; ConvaTec). Fifty consecutive patients were then
      evaluated with the new dressing to complete the audit cycle. Clinical outcome
      measures were wear time, number of changes, blister rate and length of hospital
      stay. Statistical comparisons were performed using Mann Whitney or Fisher's exact
      test (statistical significance p < 0.05). RESULTS: Wear time for the traditional
      dressing (2 days) was significantly shorter than for the modern dressing (7 days;
      p < 0.001), and required more changes (0 vs 3; p < 0.001). Twenty per cent of
      patients developed blisters with the traditional dressing compared with 4% with
      the modern dressing (p=0.028). Median length of stay was the same for the modern
      dressing (4 days) compared with the traditional dressing (4 days). In the modern
      dressing group, 75% of patients were discharged by day 4, whereas in the
      traditional group this took until day 6. CONCLUSION: This audit highlights the
      problems associated with traditional dressings with frequent early dressing
      changes, blistering and delayed discharge. These adverse outcomes can be
      minimised with a modern dressing specifically designed for the demands of lower
      limb arthroplasty. Units planning to implement enhanced recovery regimens should
      consider adopting this dressing to avoid compromising patient discharge.
      DECLARATION OF INTEREST: There were no external sources of funding for this
      audit; however, one author (JC) received reimbursement of expenses to attend and
      present work at educational conferences from ConvaTec.

PMID- 22584682
TI  - Resveratrol prevents TNFalpha-induced suppression of adiponectin expression via
      PPARgamma activation in 3T3-L1 adipocytes.
AB  - Tumor necrosis factor alpha (TNFalpha) is an adipokine, whose increase is known
      to suppress the expression and secretion of adiponectin in adipocytes.
      Resveratrol has been ever reported to recover the suppression of adiponectin by
      TNFalpha, but the underlying mechanism remains poorly understood. In this study,
      we validated the roles of resveratrol in the inhibition of the adiponectin by
      TNFalpha in 3T3-L1 cells. Exposure to TNFalpha for 24 h inhibited adiponectin
      synthesis and secretion, but the inhibitions were partially recovered by
      resveratrol treatment in 3T3-L1 adipocytes. Furthermore, we found that
      resveratrol improved the expression of adiponectin by the increase of PPARgamma
      DNA-binding activity. Our results suggest that resveratrol may attenuate the
      inhibition of adiponectin expression by TNFalpha via activation of PPARgamma,
      thereby possibly improving insulin resistance. However, significant preventive
      effects of resveratrol were only observed when it was administrated before
      TNFalpha increase, limiting its use as preventive strategy for insulin
      resistance.

PMID- 22584681
TI  - Chronic spontaneous urticaria: an autoimmune disease? A revision of the
      literature.
AB  - The cause of chronic spontaneous urticaria has been an enigma for decades, but
      the recognition of functional autoantibodies in some patients with the
      spontaneous chronic urticaria has opened up a new concept of autoimmune
      urticaria. Clinical and laboratory features are in keeping with an autoimmune
      aetiology for many patients with otherwise inexplicable disease, but there is
      still debate about the importance of functional autoantibodies in the disease
      pathogenesis, how to test them and the clinical implications for treatment and
      prognosis. This review will look at the evidence for there being an autoimmune
      subset of urticaria, the strengths and weaknesses of the available tests in
      current use. 

PMID- 22584683
TI  - Heterotopic ossification in high-grade open fractures sustained in combat: risk
      factors and prevalence.
AB  - OBJECTIVES: To determine the prevalence and identify the risk factors for
      heterotopic ossification (HO) formation in high-grade open fractures sustained
      during combat and to report on the results of HO excision. DESIGN: Retrospective.
      SETTING: United States Army level-1 trauma center. PATIENTS/PARTICIPANTS: Seventy
      six consecutive patients with 91 combat-related open Gustilo and Anderson type II
      and higher fractures were identified from March 1, 2003, through January 30,
      2005. Fifty-nine patients with 71 fractures met criteria for study inclusion.
      MAIN OUTCOME MEASUREMENTS: Fractures were categorized into HO-present and HO
      absent groups based on radiographic imaging. Risk factors such as injury
      mechanism, injury severity score (ISS), Gustilo and Anderson type, injury
      location, closed head injury, burn, and infection were compared between the
      groups. RESULTS: HO was present in 27 of 71 open fractures (38.1%). Variables
      associated with HO formation included ISS (p = 0.02) and injury location although
      infection and use of negative pressure therapy were not. Ten of 27 fractures with
      HO underwent excision. HO did not occur or was mild in 25 tibiae. CONCLUSIONS: HO
      is a common sequela of high-grade open fractures sustained in combat. High ISS
      and injury location to the shoulder, hip, and femur are risk factors for HO
      formation. The most common regions for HO excision were the elbow, forearm, and
      hip with mixed results. Importantly, HO did not seem to be a complication of open
      high-grade tibia fractures. LEVEL OF EVIDENCE: Prognostic Level II. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 22584684
TI  - Hepatic microRNA profiles offer predictive and mechanistic insights after
      exposure to genotoxic and epigenetic hepatocarcinogens.
AB  - In recent years, accumulating evidence supports the importance of microRNAs in
      liver physiology and disease; however, few studies have examined the involvement
      of these noncoding genes in chemical hepatocarcinogenesis. Here, we examined the
      liver microRNA profile of male Fischer rats exposed through their diet to
      genotoxic (2-acetylaminofluorene) and epigenetic (phenobarbital,
      diethylhexylphthalate, methapyrilene HCL, monuron, and chlorendic acid) chemical
      hepatocarcinogens, as well as to non-hepatocarcinogenic treatments (benzophenone,
      and diethylthiourea) for 3 months. The effects of these treatments on liver
      pathology, plasma clinical parameters, and liver mRNAs were also determined. All
      hepatocarcinogens affected the expression of liver mRNAs, while the hepatic
      microRNA profiles were associated with the mode of action of the chemical
      treatments and corresponded to chemical carcinogenicity. The three nuclear
      receptor-activating chemicals (phenobarbital, benzophenone, and
      diethylhexylphthalate) were characterized by the highly correlated induction of
      the miR-200a/200b/429, which is involved in protecting the epithelial status of
      cells and of the miR-96/182 clusters. The four non-nuclear receptor-activating
      hepatocarcinogens were characterized by the early, persistent induction of miR
      34, which was associated with DNA damage and oxidative stress in vivo and in
      vitro. Repression of this microRNA in a hepatoma cell line led to increased cell
      growth; thus, miR-34a could act to block abnormal cell proliferation in cells
      exposed to DNA damage or oxidative stress. This study supports the proposal that
      hepatic microRNA profiles could assist in the earlier evaluation and
      identification of hepatocarcinogens, especially those acting by epigenetic
      mechanisms.

PMID- 22584685
TI  - The role of endoplasmic reticulum Ca2+-independent phospholipase a2gamma in
      oxidant-induced lipid peroxidation, Ca2+ release, and renal cell death.
AB  - Oxidant-induced lipid peroxidation and cell death are major components of
      ischemia/reperfusion and toxicant injury. Our previous studies showed that renal
      proximal tubular cells (RPTCs) express Ca(2+)-independent phospholipase A(2)gamma
      (iPLA(2)gamma) in endoplasmic reticulum (ER) and mitochondria and that
      iPLA(2)gamma is cytoprotective. Our present studies reveal the role of ER
      iPLA(2)gamma in oxidant-induced ER lipid peroxidation, Ca(2+) release, and cell
      death. Oxidant tert-butyl hydroperoxide (TBHP) caused ER lipid peroxidation and
      Ca(2+) release in isolated rabbit kidney cortex microsomes. ER-iPLA(2)gamma
      inhibition, using bromoenol lactone (BEL), potentiated both oxidant-induced ER
      lipid peroxidation and Ca(2+) release. Assessment of fatty acids using
      electrospray ionization-mass spectrometry revealed that ER-iPLA(2)gamma mediates
      the TBHP-induced release of arachidonic acid (20:4), linoleic acid (18:2), and
      their oxidized forms (18:2-OH, 18:2-OOH, 20:4-OH, 20:4-OOH, 20:4-(OH)(3).
      iPLA(2)gamma inhibition also accelerated oxidant-induced ER Ca(2+) release in
      RPTC. Depletion of ER Ca(2+) stores in RPTC with thapsigargin, an ER Ca(2+) pump
      inhibitor, prior to TBHP exposure reduced necrotic cell death and blocked the
      potentiation of TBHP-induced necrotic cell death by BEL. Together, these data
      provide strong evidence that ER-iPLA(2)gamma protects renal cells from oxidant
      induced necrotic cell death by releasing unsaturated and/or oxidized fatty acids
      from ER membranes, thereby preserving ER membrane integrity and preventing ER
      Ca(2+) release.

PMID- 22584686
TI  - The threshold length for fiber-induced acute pleural inflammation: shedding light
      on the early events in asbestos-induced mesothelioma.
AB  - Suspicion has been raised that high aspect ratio nanoparticles or nanofibers
      might possess asbestos-like pathogenicity. The pleural space is a specific target
      for disease in individuals exposed to asbestos and by implication of nanofibers.
      Pleural effects of fibers depends on fiber length, but the key threshold length
      beyond which adverse effects occur has never been identified till now because all
      asbestos and vitreous fiber samples are heterogeneously distributed in their
      length. Nanotechnology advantageously allows for highly defined length
      distribution of synthetically engineered fibers that enable for in-depth
      investigation of this threshold length. We utilized the ability to prepare silver
      nanofibers of five defined length classes to demonstrate a threshold fiber length
      for acute pleural inflammation. Nickel nanofibers and carbon nanotubes were then
      used to strengthen the relationship between fiber length and pleural
      inflammation. A method of intrapleural injection of nanofibers in female C57Bl/6
      strain mice was used to deliver the fiber dose, and we then assessed the acute
      pleural inflammatory response. Chest wall sections were examined by light and
      scanning electron microscopy to identify areas of lesion; furthermore, cell
      nanowires interaction on the mesothelial surface of the parietal pleura in vivo
      was investigated. Our results showed a clear threshold effect, demonstrating that
      fibers beyond 4 um in length are pathogenic to the pleura. The identification of
      the threshold length for nanofiber-induced pathogenicity in the pleura has
      important implications for understanding the structure-toxicity relationship for
      asbestos-induced mesothelioma and consequent risk assessment with the aim to
      contribute to the engineering of synthetic nanofibers by the adoption of a benign
      by-design approach.

PMID- 22584688
TI  - Photofunctional hybrids of rare earth complexes covalently bonded to ZnO core
      shell nanoparticle substrate through polymer linkage.
AB  - A novel series of multi-component hybrids are assembled based on rare earth
      coordinated to rare earth ion (Eu(3+), Tb(3+), Sm(3+), Dy(3+)) complex systems
      and ZnO nanocomposites through three different ester units (ethyl methacrylate
      (EMA), 2-hydroxyethyl methacrylate (HEMA) and 2,2,3,4,4,4-hexafluorobutyl
      methacrylate (HFMA)) as functional polymer linkages. Methacrylic-group-modified
      ZnO nanoparticles (designated ZnO-MAA) are synthesized based on the reaction
      between zinc methacrylate and LiOH with the molar ratio 1 : 3.5 via sol-gel
      process. The final hybrid materials are prepared by introducing rare earth
      complexes into ZnO-MAA matrix via addition polymerization reaction in the
      presence of benzoyl peroxide (BPO) as the initiator. The detailed
      characterization and luminescence of these hybrid materials are discussed. It is
      found that ZnO-MAA-HEMA/EMA/HFBMA-RE-phen hybrid systems have effective
      intramolecular energy transfer process and exhibit longer lifetime and higher
      quantum efficiency.

PMID- 22584687
TI  - Comparative computational modeling of airflows and vapor dosimetry in the
      respiratory tracts of rat, monkey, and human.
AB  - Computational fluid dynamics (CFD) models are useful for predicting site-specific
      dosimetry of airborne materials in the respiratory tract and elucidating the
      importance of species differences in anatomy, physiology, and breathing patterns.
      We improved the imaging and model development methods to the point where CFD
      models for the rat, monkey, and human now encompass airways from the nose or
      mouth to the lung. A total of 1272, 2172, and 135 pulmonary airways representing
      17+/-7, 19+/-9, or 9+/-2 airway generations were included in the rat, monkey and
      human models, respectively. A CFD/physiologically based pharmacokinetic model
      previously developed for acrolein was adapted for these anatomically correct
      extended airway models. Model parameters were obtained from the literature or
      measured directly. Airflow and acrolein uptake patterns were determined under
      steady-state inhalation conditions to provide direct comparisons with prior data
      and nasal-only simulations. Results confirmed that regional uptake was sensitive
      to airway geometry, airflow rates, acrolein concentrations, air:tissue partition
      coefficients, tissue thickness, and the maximum rate of metabolism. Nasal
      extraction efficiencies were predicted to be greatest in the rat, followed by the
      monkey, and then the human. For both nasal and oral breathing modes in humans,
      higher uptake rates were predicted for lower tracheobronchial tissues than either
      the rat or monkey. These extended airway models provide a unique foundation for
      comparing material transport and site-specific tissue uptake across a
      significantly greater range of conducting airways in the rat, monkey, and human
      than prior CFD models.

PMID- 22584690
TI  - Learning curve of thoracoscopic repair of esophageal atresia.
AB  - BACKGROUND: Thoracoscopic repair of esophageal atresia is considered to be one of
      the more advanced pediatric surgical procedures, and it undoubtedly has a
      learning curve. This is a single-center study that was designed to determine the
      learning curve of thoracoscopic repair of esophageal atresia. METHODS: The study
      involved comparison of the first and second five-year outcomes of thoracoscopic
      esophageal atresia repair. RESULTS: The demographics of the two groups were
      comparable. There was a remarkable reduction of postoperative leakage or
      stenosis, and recurrence of fistulae, in spite of the fact that nowadays the
      procedure is mainly performed by young staff members and fellows. CONCLUSIONS:
      There is a considerable learning curve for thoracoscopic repair of esophageal
      atresia. Centers with the ambition to start up a program for thoracoscopic repair
      of esophageal atresia should do so with the guidance of experienced centers.

PMID- 22584689
TI  - Intravenous lornoxicam is more effective than paracetamol as a supplemental
      analgesic after lower abdominal surgery: a randomized controlled trial.
AB  - BACKGROUND: The aim of this prospective, randomized, double-blind study was to
      determine the more effective supplemental analgesic, paracetamol or lornoxicam,
      for postoperative pain relief after lower abdominal surgery. METHODS: Sixty
      patients scheduled for lower abdominal surgery under general anesthesia were
      randomly allocated to receive either isotonic saline (control group), intravenous
      paracetamol 1 g every 6 h (paracetamol group), or lornoxicam 16 mg then 8 mg
      after 12 h (lornoxicam group). Additionally pain was treated postoperatively with
      morphine patient-controlled analgesia. Postoperative pain scores measured by the
      verbal pain score (VPS), morphine consumption, and the incidence of side effects
      were measured at 1, 2, 4, 8, 12, and 24 h postoperatively. RESULTS: Morphine
      consumption at 12 and 24 h was significantly lower in the lornoxicam group (19.25
      +/- 5.7 mg and 23.1 +/- 6.5 mg) than in the paracetamol group (23.4 +/- 6.6 mg
      and 28.6 +/- 7.6 mg). Both treatment groups had less morphine consumption than
      the control group (28.5 +/- 5 mg and 38.1 +/- 6.6 mg) at 12 and 24 h,
      respectively. Additionally, VPS was reduced in the paracetamol and the lornoxicam
      groups compared with the control group both at rest and on coughing. Further
      analysis revealed that VPS in the lornoxicam group was significantly lower than
      that in the paracetamol group only during coughing. Drug-related side effects
      were comparable in all groups. CONCLUSIONS: Lornoxicam is superior to paracetamol
      for postoperative analgesia after lower abdominal surgery. However, paracetamol
      could be an alternative supplemental analgesic whenever an NSAID is unsuitable.
      TRIAL REGISTRATION: clinicaltrials.gov.identifier:NCT01564680.

PMID- 22584691
TI  - DAD-6: A 6-ltem version of the Disability Assessment for Dementia scale which may
      differentiate Alzheimer's disease and mild cognitive impairment from controls.
AB  - BACKGROUND: The need to detect early changes in instrumental activities of daily
      life led us to modify the Disability Assessment for Dementia Scale (DAD) by
      focusing on executive components of 6 instrumental items (DAD-6). AIM: To
      evaluate the relevance of the DAD-6 for detecting early impairment in a
      nondemented population. METHODS: The DAD-6 was administered to informants of 84
      patients: 31 with mild dementia (MD), 53 with mild cognitive impairment (MCI) and
      55 healthy controls. RESULTS: DAD-6 scores gradually decreased with increasing
      severity of the cognitive status [18 in healthy controls vs. 15.1 +/- 3.2 in MCI
      versus 9.6 +/- 3.5 in MD, p < 0.0001). Receiver-operating characteristic curve
      analyses yielded an optimal cut score of 14 to distinguish MCI from MD with a
      sensitivity of 0.83 (95% confidence interval 0.74-0.92) and a specificity of 0.84
      (0.71-0.94), and a cut score of 15 to distinguish single-domain MCI from multi
      domain MCI with a sensitivity of 0.96 (0.90-0.99) and a specificity of 0.54 (0.33
      0.75). CONCLUSION: The DAD-6 reliably detects early loss of autonomy due to
      cognitive impairment.

PMID- 22584692
TI  - Volume-outcome association in bariatric surgery: a systematic review.
AB  - OBJECTIVE: To systematically examine the association between annual hospital and
      surgeon case volume and patient outcomes in bariatric surgery. BACKGROUND:
      Bariatric surgery remains a technically demanding field with significant risk for
      morbidity and mortality. To mitigate this risk, minimum annual hospital and
      surgeon case volume requirements are being set and certain hospitals are being
      designated as "Bariatric Surgery Centers of Excellence." The effects of these
      interventions on patient outcomes remain unclear. METHODS: A comprehensive
      systematic review on volume-outcome association in bariatric surgery was
      conducted by searching MEDLINE, Cochrane Database of Systematic Reviews, and
      Evidence Based Medicine Reviews databases. Abstracts of identified articles were
      reviewed and pertinent full-text versions were retrieved. Manual search of
      bibliographies was performed and relevant studies were retrieved. Methodological
      quality assessment and data extraction were completed in a systematic fashion.
      Pooling of results was not feasible due to the heterogeneity of the studies. A
      qualitative summary of results is presented. RESULTS: From a total of 2928 unique
      citations, 24 studies involving a total of 458,032 patients were selected for
      review. Two studies were prospective cohorts (level of evidence [LOE] 1), 3 were
      retrospective cohorts (LOE 3), 2 were retrospective case controls (LOE 3), and 17
      were retrospective case series (LOE 4). The overall methodological quality of the
      reviewed studies was fair. A positive association between annual surgeon volume
      and patient outcomes was reported in 11 of 13 studies. A positive association
      between annual hospital volume and patient outcomes was reported in 14 of 17
      studies. CONCLUSIONS: There is strong evidence of improved patient outcomes in
      the hands of high-volume surgeons and high-volume centers. This study supports
      the concept of "Bariatric Surgery Center of Excellence" accreditation; however,
      future research into the quality of care characteristics of successful bariatric
      programs is recommended. Understanding the characteristics of high-volume
      surgeons, which lead to improved patient outcomes, also requires further
      investigation.

PMID- 22584693
TI  - Durability of Roux-en-Y gastric bypass surgery: a meta-regression study.
AB  - OBJECTIVE: The present meta-regression pools data from reports of long-term
      follow-up (>2 years) to assess durability of the efficacy associated with Roux-en
      Y gastric bypass (RYGB) surgery. DATA SOURCES: Medline and PubMed searches for
      articles pertaining to long-term weight loss after RYGB surgery were performed.
      BACKGROUND: Various studies have consistently shown short-term (<2 years)
      efficacy of RYGB surgery for morbid obesity, corroborated by meta-analytic
      techniques. Relatively few studies have assessed efficacy over longer periods of
      time. This is the first meta-analysis to analyze long-term effects of RYGB
      surgery on weight loss. METHODS: Twenty-two reports with a total of 4206 patient
      cases were included. Sixteen of the 22 studies had multiple follow-up times,
      ranging from 2 to 12.3 years (mean: 3.6 years). An inverse variance weighted
      model and meta-regression were used to generate the pooled percent mean excess
      weight loss (EWL) and the durability of EWL over time, respectively. RESULTS:
      Meta-regression did not reveal any significant change in EWL over time. Pooled
      mean EWL was 66.5%, and there was no significant association between EWL and
      length of follow-up. CONCLUSIONS: Pooling data from multiple studies meta
      analytically revealed that weight loss after RYGB is maintained over the long
      term. Further investigation would be necessary to ascertain similar durability in
      comorbidity reduction after RYGB surgery.

PMID- 22584694
TI  - Wound protectors reduce surgical site infection: a meta-analysis of randomized
      controlled trials.
AB  - OBJECTIVE: A meta-analysis of randomized clinical trials (RCTs) was conducted to
      evaluate whether wound protectors reduce the risk of surgical site infection
      (SSI) after gastrointestinal and biliary tract surgery. BACKGROUND: The
      effectiveness of impervious wound edge protectors for reduction of SSI remains
      unclear. METHODS: A systematic review was conducted in Medline, EMBASE, and the
      Cochrane Library to identify RCTs that evaluate the risk of SSI after
      gastrointestinal and biliary surgeries with and without the use of an impervious
      wound protector. The pooled risk ratio was estimated with random-effect meta
      analysis. Sensitivity analyses were performed to examine the impact of structural
      design of wound protector, publication year, study quality, inclusion of emergent
      surgeries, preoperative antibiotic administration, and bowel preparation on the
      pooled risk of SSI. RESULTS: Of the 347 studies identified, 6 RCTs representing
      1008 patients were included. The use of a wound protector was associated with a
      significant decrease in SSI (RR = 0.55, 95% CI 0.31-0.98, P = 0.04). There was a
      nonsignificant trend toward greater protective effect in studies using a dual
      ring protector (RR = 0.31, 95% CI 0.14-0.67, P = 0.003), rather than a single
      ring protector (RR = 0.83, 95% CI 0.38-1.83, P = 0.64). Publication year (P =
      0.03) and blinding of outcome assessors (P = 0.04) significantly modified the
      effect of wound protectors on SSI. CONCLUSIONS: Our results suggest that wound
      protectors reduce rates of SSI after gastrointestinal and biliary surgery.

PMID- 22584695
TI  - Anastomotic leak is not associated with oncologic outcome in patients undergoing
      low anterior resection for rectal cancer.
AB  - OBJECTIVE: To examine the association between anastomotic leak and oncologic
      outcome after anterior resection, stratifying for defunctioning stoma.
      BACKGROUND: It has been hypothesized that anastomotic leak predisposes rectal
      cancer patients to local recurrence. Many have a defunctioning stoma to reduce
      risk of clinically significant leakage. METHODS: The records of patients
      undergoing low anterior resection (1991-2010) for rectal adenocarcinoma (<=15 cm
      from anal verge) were retrospectively analyzed using a prospectively collected
      colorectal database. Data (age, gender, stage, defunctioning stoma, neoadjuvant
      treatment, distance from anal verge, anastomotic leak) were collected. Clinical
      leakage was defined as anastomotic complication requiring intervention or
      interventional radiology within 60 days of surgery. Estimated local recurrence,
      overall survival, and disease-specific survival were compared using log-rank
      method and Cox regression analysis. RESULTS: 1127 patients were included, with
      5.6-year median follow-up. The incidence of clinical anastomotic leak was 3.5%.
      Sixteen of 677 with defunctioning stoma (2.2%) developed clinical leak; 24 of 450
      without stoma (6.3%) developed leak (P = 0.005). There were no perioperative
      deaths among patients with clinical leakage. When stratified for defunctioning
      stoma, there was no association between clinical leak and local recurrence,
      disease-free survival, or overall survival. On multivariable analysis, when
      controlling for neoadjuvant therapy, distance of tumor from anal verge,
      defunctioning stoma, and pathologic stage, clinical leak was not associated with
      time to local recurrence, disease-free survival, or overall survival.
      CONCLUSIONS: In this cohort, anastomotic leakage was not associated with risk of
      local recurrence. Defunctioning stoma was associated with lower incidence of
      clinical leakage but not with difference in oncologic outcome. Careful patient
      selection for defunctioning stoma helps reduce risk of clinically significant
      anastomotic leak.

PMID- 22584696
TI  - The role of surgeon error in withdrawal of postoperative life support.
AB  - BACKGROUND: Surgeons may be reluctant to withdraw postoperative life support
      after a poor outcome. METHODS: A cross-sectional random sample was taken from a
      US mail survey of 2100 surgeons who routinely perform high-risk operations. We
      used a hypothetical vignette of a specialty-specific operation complicated by a
      hemiplegic stroke and respiratory failure. On postoperative day 7, the patient
      and family requested withdrawal of life-supporting therapy. We experimentally
      modified the timing and role of surgeon error to assess their influence on
      surgeons' willingness to withdraw life-supporting care. RESULTS: The adjusted
      response rate was 56%. Sixty-three percent of respondents would not honor the
      request to withdraw life-supporting treatment. Willingness to withdraw life
      support was significantly lower in the setting of surgeon error (33% vs 41%, P <
      0.008) and elective operations rather than in emergency cases (33% vs 41%, P =
      0.01). After adjustment for specialty, years of experience, geographic region,
      and gender, odds of withdrawing life-supporting therapy were significantly
      greater in cases in which the outcome was not explicitly from error during an
      emergency operation as compared to iatrogenic injury in elective cases (odds
      ratio 1.95, 95% confidence intervals 1.26-3.01). Surgeons who did not withdraw
      life-support were significantly more likely to report the importance of optimism
      regarding prognosis (79% vs 62%, P < 0.0001) and concern that the patient could
      not accurately predict future quality of life (80% vs 68%, P < 0.0001).
      CONCLUSIONS: Surgeons are more reluctant to withdraw postoperative life
      supporting therapy for patients with complications from surgeon error in the
      elective setting. This may also be influenced by personal optimism and a belief
      that patients are unable to predict the value of future health states.

PMID- 22584697
TI  - Multiple endocrine neoplasias: an overview of recent progress.

PMID- 22584698
TI  - Narrowing the gap of personalized medicine in emerging countries: the case of
      multiple endocrine neoplasias in Brazil.
AB  - The finished version of the human genome sequence was completed in 2003, and this
      event initiated a revolution in medical practice, which is usually referred to as
      the age of genomic or personalized medicine. Genomic medicine aims to be
      predictive, personalized, preventive, and also participative (4Ps). It offers a
      new approach to several pathological conditions, although its impact so far has
      been more evident in mendelian diseases. This article briefly reviews the
      potential advantages of this approach, and also some issues that may arise in the
      attempt to apply the accumulated knowledge from genomic medicine to clinical
      practice in emerging countries. The advantages of applying genomic medicine into
      clinical practice are obvious, enabling prediction, prevention, and early
      diagnosis and treatment of several genetic disorders. However, there are also
      some issues, such as those related to: (a) the need for approval of a law
      equivalent to the Genetic Information Nondiscrimination Act, which was approved
      in 2008 in the USA; (b) the need for private and public funding for genetics and
      genomics; (c) the need for development of innovative healthcare systems that may
      substantially cut costs (e.g. costs of periodic medical followup); (d) the need
      for new graduate and postgraduate curricula in which genomic medicine is
      emphasized; and (e) the need to adequately inform the population and possible
      consumers of genetic testing, with reference to the basic aspects of genomic
      medicine.

PMID- 22584699
TI  - Multiple endocrine neoplasia: the Chilean experience.
AB  - Multiple endocrine neoplasia (MEN) types 1 and 2 are genetic diseases that are
      inherited as autosomal traits. The major clinical manifestations of multiple
      endocrine neoplasia type 1 include the so-called "3 P's": parathyroid, pituitary,
      and pancreatic tumors, including gastroenteroneuroendocrine tumors. Genetic
      testing can be performed on patients and the potential carriers of the menin gene
      mutation, but the genotype-phenotype correlation in multiple endocrine neoplasia
      type 1 is less straightforward than multiple endocrine neoplasia type 2. Most
      likely, the main advantage of genetic testing in MEN1 is to exclude from further
      studies those who are negative for the genetic mutation if they belong to a
      family with a known history of MEN1. In Chile, we started with rearranged during
      transfection proto-oncogene genetic testing (MEN2) 15 years ago. We carried out a
      prophylactic total thyroidectomy to prevent medullary thyroid carcinoma in a
      three-year-old girl who presented with microscopic medullary thyroid carcinoma.
      More than 90% of the individuals who tested positive using a genetic test
      achieved a biochemical cure compared with only 27% of patients who receive a
      clinical diagnosis. Mutations are mainly located in exon 11; the most common is
      C634W, rather than C634R. Hypertensive crisis was the cause of death in three
      patients, and extensive distant metastases occurred in nine (including two
      patients with multiple endocrine neoplasia type 2B) of 14 patients. Earlier
      recognition of medullary thyroid carcinoma and the other features of the disease,
      especially pheochromocytoma, will improve the survival rate of patients with
      multiple endocrine neoplasia.

PMID- 22584700
TI  - MENX and MEN4.
AB  - Multiple endocrine neoplasias are autosomal dominant disorders characterized by
      the occurrence of tumors in at least two endocrine glands. Two MEN syndromes have
      long been known and are well characterized: the MEN type 1 (MEN1) and type 2
      (MEN2). These syndromes are caused by germline mutations in the MEN1 and RET
      genes, respectively, and have a different tumor spectrum. Recently, a variant of
      the MEN syndromes arose spontaneously in a rat colony and was named MENX.
      Affected animals consistently develop multiple endocrine tumors, with a spectrum
      that shares features with both MEN1 and MEN2 human syndromes. Genetic studies
      identified a germline mutation in the Cdkn1b gene, encoding the p27 cell cycle
      inhibitor, as the causative mutation for MENX. Capitalizing on these findings,
      heterozygous germline mutations in the human homologue, CDKN1B, were searched for
      and identified in patients with multiple endocrine tumors. As a consequence of
      this discovery, a novel human MEN syndrome, named MEN4, was recognized, which is
      caused by mutations in p27. Altogether, these studies identified Cdkn1b/CDKN1B as
      a novel tumor susceptibility gene for multiple endocrine tumors in both rats and
      humans. Here we review the characteristics of the MENX and MEN4 syndromes and we
      briefly address the main function of p27 and how they are affected by MENX/4
      associated mutations.

PMID- 22584701
TI  - Head and neck paragangliomas: clinical and molecular genetic classification.
AB  - Head and neck paragangliomas are tumors arising from specialized neural crest
      cells. Prominent locations are the carotid body along with the vagal, jugular,
      and tympanic glomus. Head and neck paragangliomas are slowly growing tumors, with
      some carotid body tumors being reported to exist for many years as a painless
      lateral mass on the neck. Symptoms depend on the specific locations. In contrast
      to paraganglial tumors of the adrenals, abdomen and thorax, head and neck
      paragangliomas seldom release catecholamines and are hence rarely vasoactive.
      Petrous bone, jugular, and tympanic head and neck paragangliomas may cause
      hearing loss. The internationally accepted clinical classifications for carotid
      body tumors are based on the Shamblin Class I-III stages, which correspond to
      postoperative permanent side effects. For petrous-bone paragangliomas in the head
      and neck, the Fisch classification is used. Regarding the molecular genetics,
      head and neck paragangliomas have been associated with nine susceptibility genes:
      NF1, RET, VHL, SDHA, SDHB, SDHC, SDHD, SDHAF2 (SDH5), and TMEM127. Hereditary
      HNPs are mostly caused by mutations of the SDHD gene, but SDHB and SDHC mutations
      are not uncommon in such patients. Head and neck paragangliomas are rarely
      associated with mutations of VHL, RET, or NF1. The research on SDHA, SDHAF2 and
      TMEM127 is ongoing. Multiple head and neck paragangliomas are common in patients
      with SDHD mutations, while malignant head and neck paraganglioma is mostly seen
      in patients with SDHB mutations. The treatment of choice is surgical resection.
      Good postoperative results can be expected in carotid body tumors of Shamblin
      Class I and II, whereas operations on other carotid body tumors and other head
      and neck paragangliomas frequently result in deficits of the cranial nerves
      adjacent to the tumors. Slow growth and the tendency of hereditary head and neck
      paragangliomas to be multifocal may justify less aggressive treatment strategies.

PMID- 22584702
TI  - Familial gigantism.
AB  - Familial GH-secreting tumors are seen in association with three separate
      hereditary clinical syndromes: multiple endocrine neoplasia type 1, Carney
      complex, and familial isolated pituitary adenomas.

PMID- 22584703
TI  - RET codon 609 mutations: a contribution for better clinical managing.
AB  - Medullary thyroid carcinoma currently accounts for 5-8% of all thyroid cancers.
      The clinical course of this disease varies from extremely indolent tumors that
      can go unchanged for years to an extremely aggressive variant that is associated
      with a high mortality rate. As many as 75% of all medullary thyroid carcinomas
      are sporadic, with an average age at presentation reported as 60 years, and the
      remaining 25% are hereditary with an earlier age of presentation, ranging from 20
      to 40 years. Germline RET proto-oncogene mutations are the genetic causes of
      multiple endocrine neoplasia type 2 and a strong genotype-phenotype correlation
      exists, particularly between a specific RET codon mutation and the (a) age
      related onset and (b) thyroid tumor progression, from C-cell hyperplasia to
      medullary thyroid carcinoma and, ultimately, to nodal metastases. RET mutations
      predispose an individual to the development of medullary thyroid carcinomas and
      can also influence the individual response to RET protein receptor-targeted
      therapies. RET codon 609 point mutations are rare genetic events belonging to the
      intermediate risk category for the onset of medullary thyroid carcinoma. A large
      genealogy resulting in a less aggressive form of medullary thyroid carcinoma is
      associated with the high penetrance of pheochromocytoma and has been reported in
      the literature. In this short review article, we comment on our previous report
      of a large multiple endocrine neoplasia type 2A kindred with the same Cys609Ser
      germline RET mutation in which, conversely, the syndrome was characterized by a
      slightly aggressive, highly penetrant form of medullary thyroid carcinoma that
      was associated with low penetrance of pheochromocytoma and primary
      hyperparathyroidism.

PMID- 22584704
TI  - Clinical and genetic aspects of familial isolated pituitary adenomas.
AB  - Pituitary adenomas represent a group of functionally diverse neoplasms with
      relatively high prevalence in the general population. Most occur sporadically,
      but inherited genetic predisposing factors are increasingly recognized. Familial
      isolated pituitary adenoma is a recently defined clinical entity, and is
      characterized by hereditary presentation of pituitary adenomas in the absence of
      clinical and genetic features of syndromic disease such as multiple endocrine
      neoplasia type 1 and Carney complex. Familial isolated pituitary adenoma is
      inherited in an autosomal dominant manner and accounted for approximately 2-3% of
      pituitary tumors in some series. Germline mutations in the aryl-hydrocarbon
      interacting protein gene are identified in around 25% of familial isolated
      pituitary adenoma kindreds. Pituitary adenomas with mutations of the aryl
      hydrocarbon interacting protein gene are predominantly somatotropinomas and
      prolactinomas, but non-functioning adenomas, Cushing disease, and thyrotropinoma
      may also occur. These tumors may present as macroadenomas in young patients and
      are often relatively difficult to control. Furthermore, recent evidence indicates
      that aryl-hydrocarbon interacting protein gene mutations occur in >10% of
      patients with sporadic macroadenomas that occur before 30 years of age, and in
      >20% of children with macroadenomas. Genetic screening for aryl-hydrocarbon
      interacting protein gene mutations is warranted in selected high-risk patients
      who may benefit from early recognition and follow-up.

PMID- 22584705
TI  - Pituitary tumors in patients with MEN1 syndrome.
AB  - We briefly review the characteristics of pituitary tumors associated with
      multiple endocrine neoplasia type 1. Multiple endocrine neoplasia type 1 is an
      autosomal-dominant disorder most commonly characterized by tumors of the
      pituitary, parathyroid, endocrine-gastrointestinal tract, and pancreas. A MEDLINE
      search for all available publications regarding multiple endocrine neoplasia type
      1 and pituitary adenomas was undertaken. The prevalence of pituitary tumors in
      multiple endocrine neoplasia type 1 may vary from 10% to 60% depending on the
      studied series, and such tumors may occur as the first clinical manifestation of
      multiple endocrine neoplasia type 1 in 25% of sporadic and 10% of familial cases.
      Patients were younger and the time between initial and subsequent multiple
      endocrine neoplasia type 1 endocrine lesions was significantly longer when
      pituitary disease was the initial manifestation of multiple endocrine neoplasia
      type 1. Tumors were larger and more invasive and clinical manifestations related
      to the size of the pituitary adenoma were significantly more frequent in patients
      with multiple endocrine neoplasia type 1 than in subjects with non-multiple
      endocrine neoplasia type 1. Normalization of pituitary hypersecretion was much
      less frequent in patients with multiple endocrine neoplasia type 1 than in
      subjects with non-multiple endocrine neoplasia type 1. Pituitary tumors in
      patients with multiple endocrine neoplasia type 1 syndrome tend to be larger,
      invasive and more symptomatic, and they tend to occur in younger patients when
      they are the initial presentation of multiple endocrine neoplasia type 1.

PMID- 22584707
TI  - RET haplotype, not linked to the C620R activating mutation, associated with
      Hirschsprung disease in a novel MEN2 family.
AB  - Hirschsprung disease is a congenital form of aganglionic megacolon that results
      from cristopathy. Hirschsprung disease usually occurs as a sporadic disease,
      although it may be associated with several inherited conditions, such as multiple
      endocrine neoplasia type 2. The rearranged during transfection (RET) proto
      oncogene is the major susceptibility gene for Hirschsprung disease, and germline
      mutations in RET have been reported in up to 50% of the inherited forms of
      Hirschsprung disease and in 15-20% of sporadic cases of Hirschsprung disease. The
      prevalence of Hirschsprung disease in multiple endocrine neoplasia type 2 cases
      was recently determined to be 7.5% and the cooccurrence of Hirschsprung disease
      and multiple endocrine neoplasia type 2 has been reported in at least 22 families
      so far. It was initially thought that Hirschsprung disease could be due to
      disturbances in apoptosis or due to a tendency of the mutated RET receptor to be
      retained in the Golgi apparatus. Presently, there is strong evidence favoring the
      hypothesis that specific inactivating haplotypes play a key role in the fetal
      development of congenital megacolon/Hirschsprung disease. In the present study,
      we report the genetic findings in a novel family with multiple endocrine
      neoplasia type 2: a specific RET haplotype was documented in patients with
      Hirschsprung disease associated with medullary thyroid carcinoma, but it was
      absent in patients with only medullary thyroid carcinoma. Despite the limited
      number of cases, the present data favor the hypothesis that specific haplotypes
      not linked to RET germline mutations are the genetic causes of Hirschsprung
      disease.

PMID- 22584706
TI  - Variable clinical expression in patients with a germline MEN1 disease gene
      mutation: clues to a genotype-phenotype correlation.
AB  - Multiple endocrine neoplasia type 1 is an inherited endocrine tumor syndrome,
      predominantly characterized by tumors of the parathyroid glands,
      gastroenteropancreatic tumors, pituitary adenomas, adrenal adenomas, and
      neuroendocrine tumors of the thymus, lungs or stomach. Multiple endocrine
      neoplasia type 1 is caused by germline mutations of the multiple endocrine
      neoplasia type 1 tumor suppressor gene. The initial germline mutation, loss of
      the wild-type allele, and modifying genetic and possibly epigenetic and
      environmental events eventually result in multiple endocrine neoplasia type 1
      tumors. Our understanding of the function of the multiple endocrine neoplasia
      type 1 gene product, menin, has increased significantly over the years. However,
      to date, no clear genotype-phenotype correlation has been established. In this
      review we discuss reports on exceptional clinical presentations of multiple
      endocrine neoplasia type 1, which may provide more insight into the pathogenesis
      of this disorder and offer clues for a possible genotype-phenotype correlation.

PMID- 22584708
TI  - The Hirschsprung's-multiple endocrine neoplasia connection.
AB  - The risk of patients with Hirschsprung's disease later developing multiple
      endocrine neoplasia remains a matter of concern. The multiple endocrine neoplasia
      2-Hirschsprung's disease association has been shown to cosegregate in
      Hirschsprung's disease patients with both short- and long-segment aganglionosis,
      although patients with long-segment aganglionosis a to carry the greatest risk.
      The Hirschsprung's disease-medullary thyroid carcinoma relationship also appears
      to be bi-directional, and activation or suppression of the rearranged during
      transfection gene appeared to vary over succeeding generations within the same
      family. Rearranged during transfection gene variations are associated with both
      conditions. The cosegregation of Hirschsprung's disease and multiple endocrine
      neoplasia 2 is particularly interesting as it involves both "switch off" and
      "switch on" of the rearranged during transfection proto-oncogene in the same
      patient. This cosegregation mostly relates to the cysteine-rich area on RET620
      (the "Janus gene"). The mechanism whereby rearranged during transfection
      influences gene activation in multiple endocrine neoplasia 2 is complex, but
      genetic variations impair the rearranged during transfection tyrosine kinase
      response to tyrosine kinase activation, thus appearing to dictate downstream
      signaling cascade responses. Better understanding of the RET-620 relationship
      allows for a more cost-effective method of identifying those at risk by focusing
      rearranged during transfection gene testing to this specific area as a "hot
      spot". The clinical awareness of possible medullary thyroid carcinoma has led to
      timely intervention and early treatment of this chemo- and radioresistant tumor
      with poor prognosis. Establishment of "risk" by genetic testing has become a
      classic model of molecular medicine being integrated into patient care and
      offering rearranged during transfection directed prophylactic surgical
      management. In addition, novel approaches to treatment based on this genetic
      knowledge have already shown early promise in randomized clinical trials.

PMID- 22584709
TI  - Genotype-phenotype correlation in multiple endocrine neoplasia type 2.
AB  - Multiple endocrine neoplasia type 2 is an autosomal-dominant hereditary cancer
      syndrome caused by missense gain-of-function mutations of the rearranged during
      transfection proto-oncogene, which encodes the receptor tyrosine kinase, on
      chromosome 10. It has a strong penetrance of medullary thyroid carcinomas and can
      be associated with bilateral pheochromocytoma and primary hyperparathyroidism.
      Multiple endocrine neoplasia type 2 is divided into three varieties depending on
      its clinical features: multiple endocrine neoplasia type 2A, multiple endocrine
      neoplasia type 2B, and familial medullary thyroid carcinoma. The specific
      rearranged during transfection mutation may suggest a predilection toward a
      particular phenotype and clinical course of medullary thyroid carcinoma, with
      strong genotype-phenotype correlations. Offering rearranged during transfection
      testing is the best practice for the clinical management of patients at risk of
      developing multiple endocrine neoplasia type 2, and multiple endocrine neoplasia
      type 2 has become a classic model for the integration of molecular medicine into
      patient care. Recommendations on the timing of prophylactic thyroidectomy and
      extent of surgery are based on the classification of rearranged during
      transfection mutations into risk levels according to genotype-phenotype
      correlations. Earlier identification of patients with hereditary medullary
      thyroid carcinoma can change the presentation from clinical tumor to preclinical
      disease, resulting in a high cure rate of affected patients and a much better
      prognoses.

PMID- 22584711
TI  - Over-representation of the G12S polymorphism of the SDHD gene in patients with
      MEN2A syndrome.
AB  - OBJECTIVE: To evaluate whether germline variants of the succinate dehydrogenase
      genes might be phenotypic modifiers in patients with multiple endocrine neoplasia
      type 2. Mutations of genes encoding subunits of the succinate dehydrogenase are
      associated with hereditary paraganglioma/pheochromocytoma syndrome.
      Pheochromocytoma is one of the main manifestations of multiple endocrine
      neoplasia type 2 caused by germline mutation of the rearranged during
      transfection proto-oncogene. METHODS: Polymorphisms of the succinate
      dehydrogenase genes were analyzed in 77 rearranged during transfection mutation
      carriers, 47 patients with sporadic medullary thyroid cancer, 48 patients with
      sporadic Pheo, and 100 healthy individuals. Exons 10-16 of the rearranged during
      transfection proto-oncogene were analyzed by direct DNA sequencing, and all exons
      of the von Hippel-Lindau, succinate dehydrogenase B, and succinate dehydrogenase
      subunit D genes were tested by direct DNA sequencing and multiple ligation probe
      analysis. The G12S polymorphism of the succinate dehydrogenase subunit D gene was
      determined by restriction fragment length polymorphism. RESULTS: Of the 77
      rearranged during transfection mutation carriers, 55 from 16 families had
      multiple endocrine neoplasia type 2A, three from three families had multiple
      endocrine neoplasia type 2B, and 19 from two families had familial medullary
      thyroid carcinoma. Eight of 55 (14.5%) patients with multiple endocrine neoplasia
      type 2A had this variant whereas it was absent in multiple endocrine neoplasia
      type 2B, familial medullary thyroid carcinoma, sporadic medullary thyroid
      carcinoma, and sporadic pheochromocytoma groups, and its prevalence in controls
      was 1% (p<0.002 multiple endocrine neoplasia type 2A versus controls). No
      associations between G12S and age of manifestation, incidence of pheochromocytoma
      or hyperparathyroidism, or level of serum calcitonin were observed. CONCLUSION:
      The high prevalence of the G12S variant in patients with multiple endocrine
      neoplasia type 2A raises questions about its role as a genetic modifier, but this
      proposal remains to be established.

PMID- 22584710
TI  - Molecular mechanisms of RET receptor-mediated oncogenesis in multiple endocrine
      neoplasia 2.
AB  - Multiple endocrine neoplasia type 2 is an inherited cancer syndrome characterized
      by tumors of thyroid and adrenal tissues. Germline mutations of the REarranged
      during Transfection (RET) proto-oncogene, leading to its unregulated activation,
      are the underlying cause of this disease. Multiple endocrine neoplasia type 2 has
      been a model in clinical cancer genetics, demonstrating how knowledge of the
      genetic basis can shape the diagnosis and treatment of the disease. Here, we
      discuss the nature and effects of the most common recurrent mutations of RET
      found in multiple endocrine neoplasia type 2. Current understanding of the
      molecular mechanisms of RET mutations and how they alter the structure and
      function of the RET protein leading to its aberrant activation, and the effects
      on RET localization and signaling are described.

PMID- 22584712
TI  - Personalized medicine: caught between hope, hype and the real world.
AB  - Genomic and personalized medicine have become buzz phrases that pervade all
      fields of medicine. Rapid advances in "-omics" fields of research (chief of which
      are genomics, proteinomics, and epigenomics) over the last few years have allowed
      us to dissect the molecular signatures and functional pathways that underlie
      disease initiation and progression and to identify molecular profiles that help
      the classification of tumor subtypes and determine their natural course,
      prognosis, and responsiveness to therapies. Genomic medicine implements the use
      of traditional genetic information, as well as modern pangenomic information,
      with the aim of individualizing risk assessment, prevention, diagnosis, and
      treatment of cancers and other diseases. It is of note that personalizing medical
      treatment based on genetic information is not the revolution of the 21st century.
      Indeed, the use of genetic information, such as human leukocyte antigen-matching
      for solid organ transplantation or blood transfusion based on ABO blood group
      antigens, has been standard of care for several decades. However, in recent years
      rapid technical advances have allowed us to perform high-throughput, high-density
      molecular analyses to depict the genomic, proteinomic, and epigenomic make-up of
      an individual at a reasonable cost. Hence, the so-called genomic revolution is
      more or less the logical evolution from years of bench-based research and bench
      to-bedside translational medicine.

PMID- 22584713
TI  - Biochemical, bone and renal patterns in hyperparathyroidism associated with
      multiple endocrine neoplasia type 1.
AB  - Primary hyperparathyroidism associated with multiple endocrine neoplasia type I
      (hyperparathyroidism/multiple endocrine neoplasia type 1) differs in many aspects
      from sporadic hyperparathyroidism, which is the most frequently occurring form of
      hyperparathyroidism. Bone mineral density has frequently been studied in sporadic
      hyperparathyroidism but it has very rarely been examined in cases of
      hyperparathyroidism/multiple endocrine neoplasia type 1. Cortical bone mineral
      density in hyperparathyroidism/multiple endocrine neoplasia type 1 cases has only
      recently been examined, and early, severe and frequent bone mineral losses have
      been documented at this site. Early bone mineral losses are highly prevalent in
      the trabecular bone of patients with hyperparathyroidism/multiple endocrine
      neoplasia type 1. In summary, bone mineral disease in multiple endocrine
      neoplasia type 1 related hyperparathyroidism is an early, frequent and severe
      disturbance, occurring in both the cortical and trabecular bones. In addition,
      renal complications secondary to sporadic hyperparathyroidism are often studied,
      but very little work has been done on this issue in hyperparathyroidism/multiple
      endocrine neoplasia type 1. It has been recently verified that early, frequent,
      and severe renal lesions occur in patients with hyperparathyroidism/multiple
      endocrine neoplasia type 1, which may lead to increased morbidity and mortality.
      In this article we review the few available studies on bone mineral and renal
      disturbances in the setting of hyperparathyroidism/multiple endocrine neoplasia
      type 1. We performed a meta-analysis of the available data on bone mineral and
      renal disease in cases of multiple endocrine neoplasia type 1-related
      hyperparathyroidism.

PMID- 22584714
TI  - Diagnostic work-up of gastroenteropancreatic neuroendocrine tumors.
AB  - Neuroendocrine tumors are a heterogeneous group of malignancies that present a
      diagnostic challenge. The majority of patients (more than 60%) present with
      metastatic disease at diagnosis. The diagnosis is based on histopathology,
      imaging, and circulating biomarkers. The histopathology should contain specific
      neuroendocrine markers such as chromogranin A, synaptophysin, and neuron-specific
      enolase and also an estimate of the proliferation by Ki-67 (MIB1). Standard
      imaging procedures consist of computed tomography or magnetic resonance imaging
      together with somatostatin receptor scintigraphy. 68Ga-DOTA-octreotate scans will
      in the future replace somatostatin receptor scintigraphy because they have higher
      specificity and sensitivity. Other positron imaging tomographic scanning tracers
      that will come into clinical use are 18F-DOPA and 11C-5HTP. Neuroendocrine tumors
      secrete many different peptides and amines that can be used as circulating
      biomarkers. The most useful general marker is chromogranin A, which is both a
      diagnostic and prognostic marker in most neuroendocrine tumors. However, there is
      still a need for improved biomarkers for early detection and follow-up of
      patients during treatment. In addition, molecular imaging can be further
      developed for both detection and evaluation of treatment.

PMID- 22584715
TI  - Multiple endocrine neoplasia type 2: achievements and current challenges.
AB  - Incremental advances in medical technology, such as the development of sensitive
      hormonal assays for routine clinical care, are the drivers of medical progress.
      This principle is exemplified by the creation of the concept of multiple
      endocrine neoplasia type 2, encompassing medullary thyroid cancer,
      pheochromocytoma, and primary hyperparathyroidism, which did not emerge before
      the early 1960s. This review sets out to highlight key achievements, such as
      joint biochemical and DNA-based screening of individuals at risk of developing
      multiple endocrine neoplasia type 2, before casting a spotlight on current
      challenges which include: (i) ill-defined upper limits of calcitonin assays for
      infants and young children, rendering it difficult to implement the biochemical
      part of the integrated DNA-based/biochemical concept; (ii) our increasingly
      mobile society in which different service providers are caring for one individual
      at various stages in the disease process. With familial relationships
      disintegrating as a result of geographic dispersion, information about the
      history of the origin family may become sketchy or just unavailable. This is when
      DNA-based gene tests come into play, confirming or excluding an individual's
      genetic predisposition to multiple endocrine neoplasia type 2 even before there
      is any biochemical or clinical evidence of the disease. However, the unrivaled
      molecular genetic progress in multiple endocrine neoplasia type 2 does not come
      without a price. Screening may uncover unknown gene sequence variants
      representing either harmless polymorphisms or pathogenic mutations. In this
      setting, functional characterization of mutant cells in vitro may generate
      helpful ancillary evidence with regard to the pathogenicity of gene variants in
      comparison with established mutations.

PMID- 22584716
TI  - Temozolomide in aggressive pituitary adenomas and carcinomas.
AB  - Temozolomide is an alkylating agent used in the treatment of gliomas and, more
      recently, aggressive pituitary adenomas and carcinomas. Temozolomide methylates
      DNA and, thereby, has antitumor effects. O6-methylguanine-DNA methyltransferase,
      a DNA repair enzyme, removes the alkylating adducts that are induced by
      temozolomide, thereby counteracting its effects. A Medline search for all of the
      available publications regarding the use of temozolomide for the treatment of
      pituitary tumors was performed. To date, 46 cases of adenohypophysial tumors that
      were treated with temozolomide, including 30 adenomas and 16 carcinomas, have
      been reported. Eighteen of the 30 (60%) adenomas and 11 of the 16 (69%)
      carcinomas responded favorably to treatment. One patient with multiple endocrine
      neoplasia type 1 and an aggressive prolactin-producing adenoma was also treated
      and demonstrated a good response. No significant complications have been
      attributed to temozolomide therapy. Thus, temozolomide is an effective treatment
      for the majority of aggressive adenomas and carcinomas. Evidence indicates that
      there is an inverse correlation between levels of O6-methylguanine-DNA
      methyltransferase immunoexpression and therapeutic response. Alternatively, high
      level O6-methylguanine-DNA methyltransferase immunoexpression correlates with an
      unfavorable response. Here, we review the use of temozolomide for treating
      pituitary neoplasms.

PMID- 22584717
TI  - Kinase inhibitors for advanced medullary thyroid carcinoma.
AB  - The recent availability of molecular targeted therapies leads to a
      reconsideration of the treatment strategy for patients with distant metastases
      from medullary thyroid carcinoma. In patients with progressive disease, treatment
      with kinase inhibitors should be offered.

PMID- 22584718
TI  - Total parathyroidectomy in a large cohort of cases with hyperparathyroidism
      associated with multiple endocrine neoplasia type 1: experience from a single
      academic center.
AB  - Most cases of sporadic primary hyperparathyroidism present disturbances in a
      single parathyroid gland and the surgery of choice is adenomectomy. Conversely,
      hyperparathyroidism associated with multiple endocrine neoplasia type 1
      (hyperparathyroidism/multiple endocrine neoplasia type 1) is an asynchronic,
      asymmetrical multiglandular disease and it is surgically approached by either
      subtotal parathyroidectomy or total parathyroidectomy followed by parathyroid
      auto-implant to the forearm. In skilful hands, the efficacy of both approaches is
      similar and both should be complemented by prophylactic thymectomy. In a single
      academic center, 83 cases of hyperparathyroidism/ multiple endocrine neoplasia
      type 1 were operated on from 1987 to 2010 and our first surgical choice was total
      parathyroidectomy followed by parathyroid auto-implant to the non-dominant
      forearm and, since 1997, associated transcervical thymectomy to prevent thymic
      carcinoid. Overall, 40% of patients were given calcium replacement (mean intake
      1.6 g/day) during the first months after surgery, and this fell to 28% in
      patients with longer follow-up. These findings indicate that several months may
      be needed in order to achieve a proper secretion by the parathyroid auto-implant.
      Hyperparathyroidism recurrence was observed in up to 15% of cases several years
      after the initial surgery. Thus, long-term follow-up is recommended for such
      cases. We conclude that, despite a tendency to subtotal parathyroidectomy
      worldwide, total parathyroidectomy followed by parathyroid auto-implant is a
      valid surgical option to treat hyperparathyroidism/multiple endocrine neoplasia
      type 1. Larger comparative systematic studies are needed to define the best
      surgical approach to hyperparathyroidism/multiple endocrine neoplasia type 1.

PMID- 22584719
TI  - Primary hyperparathyroidism in multiple endocrine neoplasia type 1: when to
      perform surgery?
AB  - Primary hyperparathyroidism is a common endocrinological disorder. In rare
      circumstances, it is associated with familial syndromes, such as multiple
      endocrine neoplasia type 1. This syndrome is caused by a germline mutation in the
      multiple endocrine neoplasia type 1 gene encoding the tumor-suppressor protein
      menin. Usually, primary hyperparathyroidism is the initial clinical expression in
      carriers of multiple endocrine neoplasia type 1 mutations, occurring in more than
      90% of patients and appearing at a young age (20-25 years). Multiple endocrine
      neoplasia type 1/primary hyperparathyroidism is generally accompanied by
      multiglandular disease, clinically manifesting with hypercalcemia, although it
      can remain asymptomatic for a long time and consequently not always be recognized
      early. Surgery is the recommended treatment. The goal of this short review is to
      discuss the timing of surgery in patients when primary hyperparathyroidism is
      associated with multiple endocrine neoplasia type 1.

PMID- 22584720
TI  - Surgical treatment of pancreatic endocrine tumors in multiple endocrine neoplasia
      type 1.
AB  - Surgical approaches to pancreatic endocrine tumors associated with multiple
      endocrine neoplasia type 1 may differ greatly from those applied to sporadic
      pancreatic endocrine tumors. Presurgical diagnosis of multiple endocrine
      neoplasia type 1 is therefore crucial to plan a proper intervention. Of note,
      hyperparathyroidism/multiple endocrine neoplasia type 1 should be surgically
      treated before pancreatic endocrine tumors/multiple endocrine neoplasia type 1
      resection, apart from insulinoma. Non-functioning pancreatic endocrine
      tumors/multiple endocrine neoplasia type 1 >1 cm have a high risk of malignancy
      and should be treated by a pancreatic resection associated with lymphadenectomy.
      The vast majority of patients with gastrinoma/multiple endocrine neoplasia type 1
      present with tumor lesions at the duodenum, so the surgery of choice is subtotal
      or total pancreatoduodenectomy followed by regional lymphadenectomy. The usual
      surgical treatment for insulinoma/multiple endocrine neoplasia type 1 is distal
      pancreatectomy up to the mesenteric vein with or without spleen preservation,
      associated with enucleation of tumor lesions in the pancreatic head. Surgical
      procedures for glucagonomas, somatostatinomas, and vipomas/ multiple endocrine
      neoplasia type 1 are similar to those applied to sporadic pancreatic endocrine
      tumors. Some of these surgical strategies for pancreatic endocrine
      tumors/multiple endocrine neoplasia type 1 still remain controversial as to their
      proper extension and timing. Furthermore, surgical resection of single hepatic
      metastasis secondary to pancreatic endocrine tumors/multiple endocrine neoplasia
      type 1 may be curative and even in multiple liver metastases surgical resection
      is possible. Hepatic trans-arterial chemo-embolization is usually associated with
      surgical resection. Liver transplantation may be needed for select cases.
      Finally, pre-surgical clinical and genetic diagnosis of multiple endocrine
      neoplasia type 1 syndrome and localization of multiple endocrine neoplasia type 1
      related tumors are crucial for determining the best surgical strategies in each
      individual case with pancreatic endocrine tumors.

PMID- 22584721
TI  - Surgical approach to medullary thyroid carcinoma associated with multiple
      endocrine neoplasia type 2.
AB  - We briefly review the surgical approaches to medullary thyroid carcinoma
      associated with multiple endocrine neoplasia type 2 (medullary thyroid
      carcinoma/multiple endocrine neoplasia type 2). The recommended surgical
      approaches are usually based on the age of the affected carrier/patient, tumor
      staging and the specific rearranged during transfection codon mutation. We have
      focused mainly on young children with no apparent disease who are carrying a
      germline rearranged during transfection mutation. Successful management of
      medullary thyroid carcinoma in these cases depends on early diagnosis and
      treatment. Total thyroidectomy should be performed before 6 months of age in
      infants carrying the rearranged during transfection 918 codon mutation, by the
      age of 3 years in rearranged during transfection 634 mutation carriers, at 5
      years of age in carriers with level 3 risk rearranged during transfection
      mutations, and by the age of 10 years in level 4 risk rearranged during
      transfection mutations. Patients with thyroid tumor >5 mm detected by ultrasound,
      and basal calcitonin levels >40 pg/ml, frequently have cervical and upper
      mediastinal lymph node metastasis. In the latter patients, total thyroidectomy
      should be complemented by extensive lymph node dissection. Also, we briefly
      review our data from a large familial medullary thyroid carcinoma genealogy
      harboring a germline rearranged during transfection Cys620Arg mutation. All 14
      screened carriers of the rearranged during transfection Cys620Arg mutation who
      underwent total thyroidectomy before the age of 12 years presented persistently
      undetectable serum levels of calcitonin (<2 pg/ml) during the follow-up period of
      2-6 years. Although it is recommended that preventive total thyroidectomy in
      rearranged during transfection codon 620 mutation carriers is performed before
      the age of 5 years, in this particular family the surgical intervention performed
      before the age of 12 years led to an apparent biochemical cure.

PMID- 22584722
TI  - Surgical approach in patients with hyperparathyroidism in multiple endocrine
      neoplasia type 1: total versus partial parathyroidectomy.
AB  - Usually, primary hyperparathyroidism is the first endocrinopathy to be diagnosed
      in patients with multiple endocrine neoplasia type 1, and is also the most common
      one. The timing of the surgery and strategy in multiple endocrine neoplasia type
      1/hyperparathyroidism are still under debate. The aims of surgery are to: 1)
      correct hypercalcemia, thus preventing persistent or recurrent
      hyperparathyroidism; 2) avoid persistent hypoparathyroidism; and 3) facilitate
      the surgical treatment of possible recurrences. Currently, two types of surgical
      approach are indicated: 1) subtotal parathyroidectomy with removal of at least 3
      3 K glands; and 2) total parathyroidectomy with grafting of autologous
      parathyroid tissue. Transcervical thymectomy must be performed with both of these
      procedures. Unsuccessful surgical treatment of hyperparathyroidism is more
      frequently observed in multiple endocrine neoplasia type 1 than in sporadic
      hyperparathyroidism. The recurrence rate is strongly influenced by: 1) the lack
      of a pre-operative multiple endocrine neoplasia type 1 diagnosis; 2) the
      surgeon's experience; 3) the timing of surgery; 4) the possibility of performing
      intra-operative confirmation (histologic examination, rapid parathyroid hormone
      assay) of the curative potential of the surgical procedure; and, 5) the surgical
      strategy. Persistent hyperparathyroidism seems to be more frequent after subtotal
      parathyroidectomy than after total parathyroidectomy with autologous graft of
      parathyroid tissue. Conversely, recurrent hyperparathyroidism has a similar
      frequency in the two surgical strategies. To plan further operations, it is very
      helpful to know all the available data about previous surgery and to undertake
      accurate identification of the site of recurrence.

PMID- 22584723
TI  - Retroperitoneoscopic adrenalectomy in pheochromocytoma.
AB  - Since the first laparoscopic adrenalectomy, the technique has evolved and it has
      become the standard of care for many adrenal diseases, including
      pheochromocytoma. Two laparoscopic accesses to the adrenal have been developed:
      transperitoneal and retroperitoneal. Retroperitoneoscopic adrenalectomy may be
      recommended for the treatment of pheochromocytoma with the same peri-operative
      outcomes of the transperitoneal approach because it allows direct access to the
      adrenal glands without increasing the operative risks. Although technically more
      demanding than the transperitoneal approach, retroperitoneoscopy can shorten the
      mean operative time, which is critical for cases with pheochromocytoma where
      minimizing the potential for intra-operative hemodynamic changes is essential.
      Blood loss and the convalescence time can be also shortened by this approach.
      There is no absolute indication for either the transperitoneal or retroperitoneal
      approach; however, the latter procedure may be the best option for patients who
      have undergone previous abdominal surgery and obese patients. Also,
      retroperitoneoscopic adrenalectomy is a good alternative for treating cases with
      inherited pheochromocytomas, such as multiple endocrine neoplasia type 2A, in
      which the pheochromocytoma is highly prevalent and frequently occurs bilaterally.

PMID- 22584724
TI  - Post-surgical follow-up of primary hyperparathyroidism associated with multiple
      endocrine neoplasia type 1.
AB  - The bone mineral density increments in patients with sporadic primary
      hyperparathyroidism after parathyroidectomy have been studied by several
      investigators, but few have investigated this topic in primary
      hyperparathyroidism associated with multiple endocrine neoplasia type 1. Further,
      as far as we know, only two studies have consistently evaluated bone mineral
      density values after parathyroidectomy in cases of primary hyperparathyroidism
      associated with multiple endocrine neoplasia type 1. Here we revised the impact
      of parathyroidectomy (particularly total parathyroidectomy followed by autologous
      parathyroid implant into the forearm) on bone mineral density values in patients
      with primary hyperparathyroidism associated with multiple endocrine neoplasia
      type 1. Significant increases in bone mineral density in the lumbar spine and
      femoral neck values were found, although no short-term (15 months) improvement in
      bone mineral density at the proximal third of the distal radius was observed.
      Additionally, short-term and medium-term calcium and parathyroid hormone values
      after parathyroidectomy in patients with primary hyperparathyroidism associated
      with multiple endocrine neoplasia type 1 are discussed. In most cases, this
      surgical approach was able to restore normal calcium/parathyroid hormone levels
      and ultimately lead to discontinuation of calcium and calcitriol supplementation.

PMID- 22584725
TI  - Surgical management of pancreatico-duodenal tumors in multiple endocrine
      neoplasia syndrome type 1.
AB  - Pancreatico-duodenal tumors are the second most common endocrinopathy in multiple
      endocrine neoplasia syndrome type 1, and have a pronounced effect on life
      expectancy as the principal cause of disease-related death. Previous discussions
      about surgical management have focused mainly on syndromes of hormone excess and,
      in particular, the management of multiple endocrine neoplasia syndrome type 1
      related Zollinger-Ellison syndrome. Since hormonal syndromes tend to occur late
      and indicate the presence of metastases, screening with biochemical markers and
      endoscopic ultrasound is recommended for early detection of pancreatico-duodenal
      tumors, and with early surgery before metastases have developed. Surgery is
      recommended in patients with or without hormonal syndromes in the absence of
      disseminated liver metastases. The suggested operation includes distal 80%
      subtotal pancreatic resection together with enucleation of tumors in the head of
      the pancreas, and in cases with Zollinger-Ellison syndrome, excision of duodenal
      gastrinomas together with clearance of regional lymph node metastases. This
      strategy, with early and aggressive surgery before metastases have developed, is
      believed to reduce the risks for tumor recurrence and malignant progression.

PMID- 22584726
TI  - Integration of disease-specific single nucleotide polymorphisms, expression
      quantitative trait loci and coexpression networks reveal novel candidate genes
      for type 2 diabetes.
AB  - AIMS/HYPOTHESIS: While genome-wide association studies (GWASs) have been
      successful in identifying novel variants associated with various diseases, it has
      been much more difficult to determine the biological mechanisms underlying these
      associations. Expression quantitative trait loci (eQTL) provide another dimension
      to these data by associating single nucleotide polymorphisms (SNPs) with gene
      expression. We hypothesised that integrating SNPs known to be associated with
      type 2 diabetes with eQTLs and coexpression networks would enable the discovery
      of novel candidate genes for type 2 diabetes. METHODS: We selected 32 SNPs
      associated with type 2 diabetes in two or more independent GWASs. We used
      previously described eQTLs mapped from genotype and gene expression data
      collected from 1,008 morbidly obese patients to find genes with expression
      associated with these SNPs. We linked these genes to coexpression modules, and
      ranked the other genes in these modules using an inverse sum score. RESULTS: We
      found 62 genes with expression associated with type 2 diabetes SNPs. We validated
      our method by linking highly ranked genes in the coexpression modules back to
      SNPs through a combined eQTL dataset. We showed that the eQTLs highlighted by
      this method are significantly enriched for association with type 2 diabetes in
      data from the Wellcome Trust Case Control Consortium (WTCCC, p = 0.026) and the
      Gene Environment Association Studies (GENEVA, p = 0.042), validating our
      approach. Many of the highly ranked genes are also involved in the regulation or
      metabolism of insulin, glucose or lipids. CONCLUSIONS/INTERPRETATION: We have
      devised a novel method, involving the integration of datasets of different
      modalities, to discover novel candidate genes for type 2 diabetes.

PMID- 22584727
TI  - Insulin clearance: confirmation as a highly heritable trait, and genome-wide
      linkage analysis.
AB  - AIMS/HYPOTHESIS: We have previously documented a high heritability of insulin
      clearance in a Hispanic cohort. Here, our goal was to confirm the high
      heritability in a second cohort and search for genetic loci contributing to
      insulin clearance. METHODS: Hyperinsulinaemic-euglycaemic clamps were performed
      in 513 participants from 140 Hispanic families. Heritability was estimated for
      clamp-derived insulin clearance and a two-phase genome-wide linkage scan was
      conducted using a variance components approach. Linkage peaks were further
      investigated by candidate gene association analysis in two cohorts. RESULTS: The
      covariate-adjusted heritability of insulin clearance was 73%, indicating that the
      majority of the phenotypic variance is due to genetic factors. In the Phase 1
      linkage scan, no signals with a logarithm of odds (LOD) score >2 were detected.
      In the Phase 2 scan, two linkage peaks with an LOD >2 for insulin clearance were
      identified on chromosomes 15 (LOD 3.62) and 20 (LOD 2.43). These loci harbour
      several promising candidate genes for insulin clearance, with 12 single
      nucleotide polymorphisms (SNPs) on chromosome 15 and six SNPs on chromosome 20
      being associated with insulin clearance in both Hispanic cohorts.
      CONCLUSIONS/INTERPRETATION: In a second Hispanic cohort, we confirmed that
      insulin clearance is a highly heritable trait and identified chromosomal loci
      that harbour genes regulating insulin clearance. The identification of such genes
      may improve our understanding of how the body clears insulin, thus leading to
      improved risk assessment, diagnosis, prevention and therapy of diabetes, as well
      as of other hyperinsulinaemic disorders, such as the metabolic syndrome and
      polycystic ovary syndrome.

PMID- 22584728
TI  - A community and culture-centered approach to developing effective cardiovascular
      health messages.
AB  - OBJECTIVE: Little is known about how best to target cardiovascular health
      promotion messages to minorities. This study describes key lessons that emerged
      from a community and culture-centered approach to developing a multimedia,
      coronary heart disease (CHD) patient education program (PEP) for medically
      underserved South Asian immigrants. METHODS: The prototype PEP integrated the
      surface structures (e.g. language) and deeper structures (e.g. explanatory models
      (EMs), values) of South Asians' socio-cultural context. Seven focus groups and 13
      individual interviews were used to investigate South Asians' reactions and obtain
      qualitative feedback after viewing the culturally targeted PEP. Qualitative data
      were organized into emergent thematic constructs. RESULTS: Participants (n=56)
      mean age was 51 years and 48 % were Hindi speakers. Community members had a
      strong, negative reaction to some of the targeted messages, "This statement is a
      bold attack. You are pin-pointing one community." Other important themes emerged
      from focus groups and interviews about the PEP: 1) it did not capture the
      community's heterogeneity; 2) did not sufficiently incorporate South Asians' EMs
      of CHD; and 3) did not address economic barriers to CHD prevention. Feedback was
      used to revise the PEP. CONCLUSION: A community and culture-centered approach to
      developing cardiovascular health promotion messages revealed tensions between the
      researcher's vantage point of "cultural targeting" and the community's
      perceptions and reactions to these messages. Engaging communities in every phase
      of message design, incorporating their EMs, recognizing community heterogeneity,
      and addressing economic and structural barriers, are critical steps to ensuring
      that health promotion messages reach their intended audience and achieve true
      cultural appropriateness.

PMID- 22584730
TI  - Effects of sling and voluntary constraint during constraint-induced movement
      therapy for the arm after stroke: a randomized, prospective, single-centre,
      blinded observer rated study.
AB  - OBJECTIVE: To determine whether a combination of constraint-induced movement
      therapy and physiotherapy in stroke patients using different constraint regimens
      (sling versus voluntary constraint) changes or reduces motor deficits, the amount
      of functional use of the arm and whether the effects of treatment continue after
      12 months. DESIGN: Forty-seven stroke patients were stratified and randomly
      divided into intensive physiotherapy programmes focused on regaining arm
      functions. SETTING: Neurorehabilitation Unit of IInd Department of Neurology at
      Institute of Psychiatry and Neurology in Warsaw. SUBJECT: Patients were randomly
      allocated to: the sling-constraint group (n = 24) or to the voluntary-constraint
      group (n = 23). INTERVENTIONS: Massed practice with the paretic arm (5 hours/day
      for 15 consecutive working days). Sling-constraint group had their arm
      immobilized in a hemi-sling during therapy. In addition, individual, 1-hour
      physiotherapy sessions were conducted in both groups. MAIN MEASURES: Rivermead
      Motor Assessment (RMA) Arm scale, (0-15), Motor Activity Log - Quality of
      Movement (MAL-QOM) (0-5 for 30 daily tasks). RESULTS: There was no significant
      difference between groups after therapy (MAL-QOM mean change for sling group
      0.78, SD = 0.46 and for voluntary-constraint group 0.84, SD = 0.48; P = 0.687).
      All treated patients retained mean gains in real-world arm use (MAL-QOM) mean
      scores after 12 months follow-up compared with posttreatment values but there was
      no significant difference between groups (comparison of estimated mean change of
      MAL-QOM stated 0.23. 95% confidence interval = -0.04-0.50). CONCLUSION: Voluntary
      activity constraint in the intact arm is equivalent to sling, standard constraint
      during massed practice of paretic arm.

PMID- 22584729
TI  - Leiomyoma: genetics, assisted reproduction, pregnancy and therapeutic advances.
AB  - PURPOSE: Uterine leiomyomas are common, benign, reproductive tract tumors
      affecting a majority of reproductive aged women. They are associated with
      gynecologic morbidity and detrimentally affect reproductive potential. The
      etiology of leiomyomas is poorly understood and their diagnosis prior to
      treatment with Assisted Reproductive Technologies (ART) represents a management
      dilemma. The purpose of this paper is to review known genetic and molecular
      contributions to the etiologies of leiomyomas, describe their impact on ART
      outcomes and reproductive potential, and review alternative therapies and future
      directions in management. METHODS: A critical review of the literature pertaining
      to genetic component of uterine leiomyomas, their impact on ART and pregnancy and
      leiomyoma therapeutics was performed. RESULTS: Uterine leiomyomas are
      characterized by complex molecular mechanisms. Their location and size determines
      their potential detriment to ART and reproductive function and novel therapeutic
      modalities are being developed. CONCLUSION: The high prevalence of uterine
      leiomyomas and their potential detrimental influence on ART and reproductive
      function warrants continued well-designed studies to ascertain their etiology,
      optimal treatment and novel less morbid therapies.

PMID- 22584731
TI  - Naturally occurring himachalenes to benzocycloheptene amino vinyl bromide
      derivatives: as antidepressant molecules.
AB  - A new series of benzocycloheptene amino vinyl bromide derivatives (9a-9m) were
      synthesized from isomeric mixture of himachalenes through two-step synthesis. The
      unusual structure of benzocycloheptene amino vinyl bromide derivative (9a) was
      confirmed by NMR and X-ray crystallography analyses. The newly synthesized amino
      vinyl bromide derivatives of benzocycloheptene were further evaluated for their
      antidepressant activities. The compound 9c had shown significant reduction in the
      immobility period.

PMID- 22584732
TI  - Prevalence and risk factors for insomnia among breast cancer patients on
      aromatase inhibitors.
AB  - PURPOSE: Insomnia is increasingly recognized as a major symptom outcome in breast
      cancer; however, little is known about its prevalence and risk factors among
      women receiving aromatase inhibitors (AIs), a standard treatment to increase
      disease-free survival among breast cancer patients. METHODS: A cross-sectional
      survey study was conducted among postmenopausal women with stage 0-III breast
      cancer receiving adjuvant AI therapy at an outpatient breast oncology clinic of a
      large university hospital. The insomnia severity index (ISI) was used as the
      primary outcome. Multivariate logistic regression analyses were performed to
      evaluate risk factors. RESULTS: Among 413 participants, 130 (31.5 %) had
      subthreshold insomnia on the ISI, and 77 (18.64 %) exceeded the threshold for
      clinically significant insomnia. In a multivariate logistic regression model,
      clinically significant insomnia was independently associated with severe joint
      pain (adjusted odds ratio (AOR) 4.84, 95 % confidence interval (CI) 1.71-13.69, P
      = 0.003), mild/moderate hot flashes (AOR 2.28, 95 % CI 1.13-4.60, P = 0.02),
      severe hot flashes (AOR 2.29, 95 % CI 1.23-6.81, P = 0.015), anxiety (AOR 1.99,
      95 % CI 1.08-3.65, P = 0.027), and depression (AOR 3.57, 95 % CI 1.48-8.52, P =
      0.004). Age (>65 vs. <55 years; AOR 2.31; 95 % CI 1.11-4.81; P = 0.026) and time
      since breast cancer diagnosis (<2 vs. 2-5 years; AOR 1.94; 95 % CI 1.02-3.69; P =
      0.045) were also found to be significant risk factors. Clinical insomnia was more
      common among those who used medication for treating insomnia and pain.
      CONCLUSIONS: Insomnia complaints exceed 50 % among AI users. Clinically
      significant insomnia is highly associated with joint pain, hot flashes, anxiety
      and depression, age, and time since diagnosis.

PMID- 22584734
TI  - Abstracts of the 19th European Congress on Obesity (ECO2012). Lyon, France. May 9
      12, 2012.

PMID- 22584733
TI  - Taxane-induced peripheral neuropathy and health-related quality of life in
      postoperative breast cancer patients undergoing adjuvant chemotherapy: N-SAS BC
      02, a randomized clinical trial.
AB  - PURPOSE: To elucidate whether adjuvant taxane monotherapy is a feasible and
      tolerable for postoperative breast cancer patients, we evaluated the severity of
      chemotherapy-induced peripheral neuropathy (CIPN) and the relative tolerability
      of regimens by health-related quality of life (HRQOL) assessment in node-positive
      breast cancer patients treated with taxane-containing regimens. METHODS: We
      evaluated CIPN and HRQOL in the first 300 patients enrolled in a larger (1,060
      total) multicenter phase III trial randomized to one of four adjuvant regimens:
      (1) anthracycline-cyclophosphamide followed by paclitaxel (ACP), (2) AC followed
      by docetaxel (ACD), (3) paclitaxel alone (PTX), or (4) docetaxel alone (DTX).
      CIPN was assessed by the Patient Neurotoxicity Questionnaire (PNQ) and the
      National Cancer Institute Common Toxicity Criteria, and HRQOL by Functional
      Assessment of Cancer Therapy-General (FACT-G). CIPN and HRQOL scores were
      compared between ACP and ACD vs. PTX and DTX, and ACP and PTX vs. ACD and DTX.
      RESULTS: PNQ sensory scores were significantly higher in patients treated with
      taxane monotherapy compared to treatment with AC followed by taxane (P = .003).
      No significant differences in PNQ sensory scores were observed between the ACP
      and PTX vs. ACD and DTX regimens (P = .669). Regardless of taxane regimen, PNQ
      severity scores for CIPN appear to be largely reversible within 1 year of
      adjuvant treatment. No significant difference in FACT-G scores was observed
      between any regimens during the study treatments. CONCLUSIONS: Patient-reported
      CIPN was significantly more severe with single-agent adjuvant taxane compared to
      AC followed by taxane treatment; however, the HRQOL findings support that single
      agent taxane treatment is tolerable.

PMID- 22584736
TI  - Statistically speaking.

PMID- 22584735
TI  - Mutations of the AMH type II receptor in two extended families with persistent
      Mullerian duct syndrome: lack of phenotype/genotype correlation.
AB  - Our goal was to compare phenotype and genotype in two extended Middle-Eastern
      families affected by persistent Mullerian duct syndrome due to mutations of the
      type II anti-Mullerian hormone receptor (AMHR-II). The first, consanguineous,
      family consisted of 6 boys and 2 girls, the second consisted of 4 girls and 2
      boys. In family I, 4 boys and 1 girl were homozygous for a stop mutation in the
      9th exon of AMHR-II, removing part of the intracellular domain of the protein. In
      family II, 1 girl and 1 boy were homozygous for a transversion changing conserved
      histidine 254 into a glutamine. Both homozygous girls were normal. In the
      homozygous males, the degree of development of Mullerian derivatives was
      variable. The uterus was well developed in 2 boys of family I and in the patient
      from family II; however, in 1 subject from family I, Mullerian derivatives were
      undetectable. Taken together, the diversity of clinical symptoms within the same
      sibship and the lack of correlation between the development of the Mullerian
      derivatives and the severity of the molecular defects suggest highly variable
      penetrance of the abnormal alleles and/or the existence of other genetic or
      epigenetic modifiers of gene expression.

PMID- 22584737
TI  - The impact of atraumatic vs conventional dressings on pain and stress.
AB  - OBJECTIVE: To compare the pain and stress experiences of patients with chronic
      wounds being treated with atraumatic vs conventional dressings at dressing
      change. METHOD: This exploratory study adopted an independent samples design to
      identify any differences between reported levels of pain and stress associated
      with the use of atraumatic and conventional dressings used in treatment regimens
      of patients with chronic wounds. Physiological and psychological assessments of
      pain and stress were recorded at dressing change (including numerical ratings,
      heart rate, blood pressure, respiration rate, GSR, salivary cortisol and the
      Perceived Stress Scale (PSS) and State Trait Anxiety Inventory (STAI)
      questionnaire surveys). RESULTS: In total, 49 patients with chronic wounds took
      part in the study. Fifty-three percent of patients were male (n=26) and 47% were
      female (n=23). Patients were aged 38-95 years, with a mean age of 69.11 +/- 14.08
      years. Overall, 10 patients were receiving atraumatic dressings with Safetac
      technology as part of their routine wound treatment and 39 were receiving
      conventional dressings. Patients receiving atraumatic dressings reported
      significantly lower numerical pain and stress ratings and experienced
      significantly lower GSR at dressing change. Mean heart rate, blood pressure,
      salivary cortisol were also lower for patients with atraumatic dressings.
      However, patients' PSS (atraumatic=24.60, conventional=22.72) and STAI
      (atraumatic=34.90, conventional=33.21) scores were similar for both dressing type
      groups. CONCLUSION: This study provides a basis for understanding how different
      dressing types can impact pain and stress at dressing change. Acute episodes of
      pain and stress were much lower in patients receiving atraumatic dressings;0
      however factors associated with the overall experience of living with a chronic
      wound may be contributing to underlying and ongoing feelings of stress and
      anxiety. The impact of these implications on selection of dressings and cost of
      care are also discussed. DECLARATION OF INTEREST: This research was commissioned
      by Molnlycke Health Care. None of the authors work for Molnlycke Health Care of
      have any financial interests with the company. There are no additional conflicts
      of interest to declare.

PMID- 22584738
TI  - Reducing the cost of lower limb wound management through industry partnership and
      staff education.
AB  - Following an audit of practice in North East London Foundation Trust (NELFT),
      obstacles in the management of lower limb conditions were identified. An
      appraisal of needs in terms of skills and theory updates for staff led to a fixed
      term 'honorary contract' between the trust and a wound-care company to facilitate
      a rolling programme of education, to upskill staff in terms of assessment and
      treatment, and develop standardised care pathways. After 3 months, a repeated
      practice audit revealed a reduction in nurse contact hours of 1156 hours. The
      partnership with industry proved to be beneficial and did not compromise care,
      and trust staff were not obligated to use their product.

PMID- 22584739
TI  - Some wounds are hard to heal:  an interesting presentation of Ehlers-Danlos
      syndrome.
AB  - A 17-year-old female patient was admitted for an elective mini laparotomy and
      cystectomy of the right ovary for the treatment of chronic supra-pubic abdominal
      pain. The procedure went without complication and she was discharged the next
      day. She was re-admitted a month later as an acute case with wound dehiscence.
      HIV serology, thyroid function, immunoglobulin, protein electrophoresis and
      electrolyte levels were all normal. There were no obvious signs of infection and
      the bacterial swabs failed to culture an organism. Despite conservative measures
      with regular dressing, oral antibiotics and input from the tissue viability team
      the wound failed to epithelialise. The wound was debrided and re-sutured a total
      of three times and the patient received 24 days of intravenous antibiotics. After
      input from various teams a diagnosis of Ehlers-Danlos syndrome was made, allowing
      for appropriate management and wound healing.

PMID- 22584740
TI  - Post-surgical scalp wounds with exposed bone treated with a plant-derived wound
      therapeutic.
AB  - OBJECTIVE: To evaluate the efficacy of a plant-derived wound dressing, a mixture
      of hypericum oil (Hypericum perforatum) and neem oil (Azadirachta indica), in
      scalp wounds with exposed bone. METHOD: A retrospective review was conducted of
      all patients presenting with scalp wounds with exposed bone following the
      excision of skin tumours and treated with a plant-derived wound dressings (1
      Primary Wound Dressing; Phytoceuticals AG), from January to July 2011. Time to
      healing, wound size, area of exposed bone, ease of handling, pain and
      complications were evaluated. RESULTS: Nine consecutive patients were analysed
      retrospectively. The patients' mean age was 81.2 +/- 8.5 years (63-90 years),
      with a mean wound size of 13.2 +/- 6.8cm(2) (0.4-22.6cm(2)) and 6.8 +/- 6.5cm(2)
      (0.3-20.7cm(2)) of exposed bone. The time to complete healing by secondary
      intention was 4-20 weeks. A rapid induction of granulation tissue was observed,
      which covered the entire exposed bone surface in six out of nine cases (67%)
      after 4 weeks, and showed a reduction in the mean area of exposed bone of 95%.
      Dressing change was easy and without pain and there were no complications.
      CONCLUSION: This retrospective, non-controlled analysis suggests that ONE is a
      very simple to use, safe and potentially effective therapy for the treatment of
      scalp wounds with exposed bone. DECLARATION OF INTEREST: There were no external
      sources of funding for this study. The authors have no conflict of interest to
      declare.

PMID- 22584741
TI  - Hair extensions--an intraoperative risk for occipital pressure ulceration.

PMID- 22584742
TI  - Total contact casting combined with human fibroblast-derived dermal tissue in 15
      DFU patients.
AB  - OBJECTIVE: To investigate the use of a cryopreserved human fibroblast-derived
      dermal substitute (Dermagraft; DG) in combination with total contact casting
      (TCC) in patients with diabetic foot ulcers, compared with previously published
      rates of healing with TCC alone. METHOD: Fifteen consecutive diabetic foot ulcer
      patients were referred to a multi-speciality clinic to be managed with a
      combination of DG and TCC, after showing no progress toward healing following at
      least 4 weeks of standard, conservative therapy. Follow-up visits were scheduled
      every 7 days, for a period of 12 weeks, or until fully healed. At each visit, DG
      and TCC were applied by the investigating clinician, and ulcer size and depth
      were recorded. Photographs were taken once a month, or when healed. If indicated,
      debridement was done to remove fibrotic tissue, callus and slough. RESULTS: The
      results demonstrated an average healing rate of 23.7 +/- 16.3 days. The average
      number of DG applications was 2.1. There was no correlation observed between
      ulcer duration, or ulcer location (forefoot or mid-foot), and time to healing;
      however, a correlation was found between wound size and healing time. CONCLUSION:
      The findings may suggest combining advanced healing modalities, such as DG with
      TCC, can be done and that they may have a benefit of limiting the time spent in
      TCC, as well as a reduction in time to heal. The study size was small and further
      studies into combining modalities are warranted to validate these findings.
      DECLARATION OF INTEREST: Both authors have been paid consultants for Advanced
      Biohealing, the producers of Dermagraft (DG). There are no financial disclosures
      for Med Efficiency, Inc. (MedE-Kast Ultra; TCC), or any other conflicts of
      interest to declare.

PMID- 22584743
TI  - The use of larval therapy to reduce the bacterial load in chronic wounds.
AB  - OBJECTIVE: To ascertain the effect of larval therapy against bacteria associated
      with infected chronic wounds, and determine if larvae therapy actively reduces
      the bacterial load in chronic wounds. METHOD: An extended literature review was
      undertaken using online databases: Athens, Medline, EMBASE, British Nursing Index
      and Allied and Complementary Medicine via OV ID and Cumulative Index to Nursing
      and Allied Health. Key terms were searched worldwide from 1950 to 2011. RESULTS:
      Four themes emerged: Gram-positive and Gram-negative bacteria, MRSA, quorum
      sensing: biofilm consideration and bacterial burden. This suggests larvae
      debridement therapy is differentially effective against both Gram-positive and
      Gram-negative bacterial strains, namely Staphylococcus aureus, Pseudomonas
      aeruginosa and meticillin-resistant Staphylococcus aureus. CONCLUSION: The
      evidence supports the use of antimicrobial properties of larvae therapy against
      the bacteria of infected chronic wounds. DECLARATION OF INTEREST: There were no
      external sources of funding for this literature review. This paper is based on an
      independent study submitted as part of the BSc Health Care Studies, (Tissue
      Viability), University of Nottingham, UK. The authors have no competing or
      financial interest to declare and ethical approval and funding were not required
      to undertake the study.

PMID- 22584745
TI  - Molecular structure and bonding in octamethylporphyrin tin(II), SnN4C28H28.
AB  - Gas-phase electron diffraction was applied for the molecular structure
      determination of octamethylporphyrin tin(II), SnN(4)C(28)H(28), at the
      temperature of 706(10) K. The molecule was found to possess C(4v) symmetry with
      the Sn atom 1.025(30) A above the plane of the N atoms and the following main
      internuclear distances (r(h1), A): Sn-N = 2.301(9), C(alpha)-N = 1.360(8),
      C(alpha)-C(beta) = 1.453(4), C(alpha)-C(m) = 1.395(4), C(beta)-C(CH3) = 1.498(4).
      Quantum chemical calculations, DFT (B3LYP, BP86, PBE, PBE0) with cc-pVDZ, cc-pVTZ
      and cc-pVQZ basis sets reproduce the experimental bond distances with accuracy
      within 0.03 A. According to NBO(B3LYP/cc-pVTZ) analysis, the direct donation
      gives a prevailing contribution to Sn-N bonding, decreasing the net charge on Sn
      from formal +2 to +1.28. The substitution effects at the pyrrole rings are
      discussed. The ability of different theoretical methods to predict the structure
      of this compound is analyzed.

PMID- 22584746
TI  - Additional value of upper GI tract endoscopy in the diagnostic assessment of
      childhood IBD.
AB  - OBJECTIVES: For the choice of treatment in children with inflammatory bowel
      disease (IBD), it is important to make a distinction between Crohn disease (CD)
      and ulcerative colitis (UC). To look for pathognomonic features of CD, upper
      gastrointestinal tract (UGT) endoscopy has become part of the routine evaluation
      of children with suspected IBD; however, pathological changes can also be found
      in the UGT in patients with UC. The aims of the present study were to establish
      the role of UGT involvement in the diagnostic assessment of suspected IBD in
      children and to detect histopathological changes in the UGT mucosa, which can
      distinguish CD from non-CD (UC and non-IBD). METHODS: Biopsies (colon, ileum,
      duodenum, stomach, esophagus) from children suspected of having IBD who underwent
      endoscopy between 2003 and 2008 were reassessed by a blinded, expert pathologist.
      The histological findings of the UGT were compared with the diagnosis based on
      ileocolonic biopsies and the final diagnosis. RESULTS: In 11% of the children
      with CD, the diagnosis was based solely on the finding of granulomatous
      inflammation in the UGT. Focal cryptitis of the duodenum and focally enhanced
      gastritis were found significantly more frequently in children with CD compared
      with children with UC and non-IBD, with a specificity and positive predictive
      value of 99% and 93% and 87.1% and 78.6%, respectively. CONCLUSIONS: Histology on
      ileocolonic biopsies alone is insufficient for a correct diagnosis of CD or UC in
      children. UGT endoscopy should, therefore, be performed in the diagnostic
      assessment of all children suspected of having IBD.

PMID- 22584747
TI  - Effect of amoxicillin/clavulanate on gastrointestinal motility in children.
AB  - AIM: The aim of the present study was to evaluate the effect of
      amoxicillin/clavulanate (A/C) on gastrointestinal motility. METHODS: Twenty
      consecutive pediatric patients referred for antroduodenal manometry received 20
      mg/kg of A/C into the small bowel lumen. In 10 patients (group A), A/C was given
      1 hour after and in 10 (group B), 1 hour before ingestion of a meal.
      Characteristics of the migrating motor complex, including presence, frequency,
      amplitude, and propagation of duodenal phase III and phase I duration and phase
      II motility index (MI), were evaluated 30 minutes before and after A/C
      administration. RESULTS: There were no statistically significant differences in
      age and sex between the 2 groups. Manometry studies were considered normal in 8
      patients in each group. In group A, 2 patients developed duodenal phase III after
      receiving A/C, and no significant difference was found in the MI before and after
      the drug administration. In group B, 9 patients developed duodenal phase III (P
      <0.05 vs group A). All phase III occurred within a few minutes from the
      medication administration. Most duodenal phase III contractions were preceded by
      an antral component during fasting but never after the medication was
      administered in either of the 2 groups (P<0.001 vs fasting). In group B, the
      duration of duodenal phase I was shorter after drug administration (P<0.05).
      There was no significant difference in duodenal phase II MI before and after A/C
      administration for the 2 study groups. CONCLUSIONS: In children, administration
      of A/C directly into the small bowel before a meal induces phase III-type
      contractions in the duodenum, with characteristics similar to those present in
      the fasting state. These data suggest the possible use of A/C as a prokinetic
      agent. Further studies are needed to clarify its specific mechanism of action and
      the group of patients most likely to benefit from its use.

PMID- 22584748
TI  - Risk of infection and prevention in pediatric patients with IBD: ESPGHAN IBD
      Porto Group commentary.
AB  - Combined immunosuppression by immunomodulators and biological therapy has become
      standard in the medical management of moderate-to-severe inflammatory bowel
      disease (IBD) because of clearly demonstrated efficacy. Clinical studies,
      registries, and case reports warn of the increased risk of infections,
      particularly opportunistic infections; however, already in the steroid
      monotherapy era, patients are at risk because it is accepted that a patient
      should be considered immunosuppressed when receiving a daily dose of 20 mg of
      prednisone for 2 weeks. Prescriptions increasingly involve azathioprine,
      methotrexate, and various biological agents. The TREAT registry evaluated safety
      in >6000 adult patients, half of them treated with infliximab (IFX) for about 1.9
      years. IFX-treated patients had an increased risk of infections and this was
      associated with disease severity and concomitant prednisone use. The REACH study,
      evaluating the efficacy of IFX in children with moderate-to-severe Crohn disease,
      refractory to immunomodulatory treatment, reports serious infections as the major
      adverse events and their frequency is higher with shorter treatment intervals.
      The combination of immunosuppressive medications is a risk factor for
      opportunistic infections. Exhaustive guidelines on prophylaxis, diagnosis, and
      management of opportunistic infections in adult patients with IBD have been
      published by a European Crohn's and Colitis Organization working group, including
      clear evidence-based statements. We have reviewed the literature on infections in
      pediatric IBD as well as the European Crohn's and Colitis Organization guidelines
      to present a commentary on infection prophylaxis for the pediatric age group.

PMID- 22584749
TI  - Reactive oxygen species in apoptosis induced by cisplatin: review of
      physiopathological mechanisms in animal models.
AB  - Cisplatin is a highly effective chemotherapeutic agent but displays significant
      ototoxic side effects. The most prominent change seen in the cochlea after
      cisplatin administration consists of loss of outer hair cells. Several mechanisms
      are believed to mediate cisplatin-induced apoptosis: binding of cisplatin to
      guanine bases on DNA and the formation of inter- and intra-strand chain cross
      linking, generation of reactive oxygen species (ROS) with increased lipid
      peroxidation and Ca(2+) influx and, finally, inflammation mediated by cisplatin.
      The aim of the present review is to analyze the role of ROS in the mechanisms
      causing cisplatin-mediated apoptosis in the inner ear and the contribution of the
      different pathways involved, emphasizing the main strategies to blockade events
      leading to apoptosis of cochlear cells.

PMID- 22584750
TI  - A device for patterned electrical stimulation of cultivated cells: preliminary
      tests with rat auditory neurons.
AB  - The number of surviving spiral ganglion neurons (SGNs) is important for the
      function of cochlear implants. Electrical stimulation has been discussed
      controversially regarding its protective effects on SGNs both in vivo and in
      vitro. The aim of this study was to develop a device for electrical stimulation
      of cultured SGNs. The developed device was first evaluated with cultivated
      fibroblasts at voltages from 10 to 60 V using biphasic rectangular pulses (pulse
      width: 10 ms, frequency: 50 Hz, stimulus burst: 1 s, interburst interval: 19 s).
      Possible toxic effects of 48 h patterned electrical stimulation were evaluated by
      propidium-iodide flow cytometry of the harvested fibroblasts. Second, the effects
      of 48-h electrical stimulation at voltages of 6 and 30 V on survival of
      cultivated SGNs were investigated as a single treatment and in the presence of
      brain-derived neurotrophic factor (BDNF, 100 ngml) in the culture medium. The
      results demonstrated constant pH and temperature behavior during electrical
      stimulation. Furthermore, no toxic effects on fibroblasts up to 40 V were found.
      The electrical stimulation of cultured neurons did not alter the survival rate
      compared to unstimulated control conditions. While BDNF application alone showed
      a significant effect on SGN survival, combination with electrical stimulation
      resulted in a not significantly increased cell survival. As a limitation of the
      study, the sensitivity of the described experimental setup appears to be low and
      only one stimulation pattern has been tested. Thus, experiments using different
      patterns of electrical stimulation and a more sensitive cultivation setup have to
      be carried out to fully investigate the effects of electrical stimulation on
      cultured SGNs. In this context, the developed device can be of help as it
      provides controlled and reproducible electrical stimulation conditions.

PMID- 22584751
TI  - Extranasopharyngeal angiofibroma: clinical and radiological presentation.
AB  - Nasopharyngeal angiofibroma (NA) is a rare, vascular tumor affecting adolescent
      males. Due to aggressive local growth, skull base location and risk of profound
      hemorrhage, NA is a challenge for surgeons. Angiofibromas have been sporadically
      described in extanasopharyngeal locations. We review ten cases of
      extranasopharyngeal angiofibroma (ENA) and discuss the incidence, clinical
      presentation and management of this pathology. The group consisted of 4 males and
      5 females aged 8-49. There were 7 patients with nasal angiofibroma, 1 patient
      with laryngeal angiofibroma, 1 patient with oral angiofibroma and another patient
      with infratemporal fossa tumor. In patients with nasal angiofibroma most common
      presenting symptoms were nasal obstruction and epistaxis. Patients with laryngeal
      angiofibroma suffered from mild dysphagia and patients with the infratemporal
      fossa tumor had painless cheek swelling. In four patients with nasal tumor
      computed tomography (CT) demonstrated mass with strong to intermediate contrast
      enhancement. In one patient with nasal tumor carotid angiography demonstrated
      pathological vessels without intensive tumor blush. Infratemporal fossa tumor
      showed intensive contrast enhancement on CT and magnetic resonance imaging (MRI)
      scans, and abundant vascularity on angiography. Laryngeal and oral angiofibroma
      required no radiological imaging. Three nasal tumors were evaluated before
      introduction of CT to clinical practice. All patients underwent surgery. No
      recurrences developed. ENAs differ significantly from NAs regarding clinical and
      radiological presentations. They lack typical clinical and radiological features
      as they develop in all age groups and in females, may be less vascularised, arise
      from various sites and produce a variety of symptoms.

PMID- 22584752
TI  - Phosphinimine-borane combinations in frustrated Lewis pair chemistry.
AB  - The phosphinimines Ph(3)PNR (R = Ph 1, C(6)F(5) 2, tBu 3) are combined with
      B(C(6)F(5))(3) in an effort to explore the frustrated Lewis pair (FLP) chemistry.
      While compound 1 is shown to form an adduct with the borane, compounds 2 and 3
      exhibit no apparent interaction. Nonetheless exposure of each of the three
      combinations to H(2) resulted in the formation of the corresponding salts
      [Ph(3)PN(H)R][HB(C(6)F(5))(3)] (R = Ph 5, C(6)F(5) 6, tBu 7). Reaction of 1 or 2
      with B(C(6)F(5))(3) and carbon dioxide afforded Ph(3)PN(R)COOB(C(6)F(5))(3) (R =
      Ph 8, C(6)F(5) 9) while the corresponding reaction with 3 gave rise only to the
      tBuNCO and (Ph(3)PO)B(C(6)F(5))(3). Reactions of 1-3 and B(C(6)F(5))(3) with
      PhC=CH proceeds to give either deprotonation or addition affording products of
      the form [Ph(3)PN(H)R][PhC=CB(C(6)F(5))(3)] or
      (Ph(3)PNR)(Ph)C=CH(B(C(6)F(5))(3)). The factors governing the nature of the
      dominant products are considered.

PMID- 22584753
TI  - Re: portal vein embolization: what do we know?

PMID- 22584754
TI  - Outcomes of prosthetic hemodialysis grafts after deployment of bare metal versus
      covered stents at the venous anastomosis.
AB  - PURPOSE: To compare postintervention patency rates after deployment of bare metal
      versus covered stents across the venous anastomosis of prosthetic arteriovenous
      (AV) grafts. METHODS: Review of our procedural database over a 6 year period
      revealed 377 procedures involving stent deployment in an AV access circuit. After
      applying strict inclusion criteria, our study group consisted of 61 stent
      deployments in 58 patients (median age 58 years, 25 men, 33 women) across the
      venous anastomosis of an upper extremity AV graft circuit that had never been
      previously stented. Both patent and thrombosed AV access circuits were
      retrospectively analyzed. Within the bare metal stent group, 20 of 32 AV grafts
      were thrombosed at initial presentation compared to 18 of 29 AV grafts in the
      covered stent group. RESULTS: Thirty-two bare metal stents and 29 covered stents
      were deployed across the venous anastomosis. The 3, 6, and 12 months primary
      access patency rates for bare metal stents were not significantly different than
      for covered stents: 50, 41, and 22 % compared to 59, 52, and 29 %, respectively
      (p = 0.21). The secondary patency rates were also not significantly different:
      78, 78, and 68 % for bare metal stents compared to 76, 69, and 61 % for covered
      stents, respectively (p = 0.85). However, covered stents demonstrated a higher
      primary stent patency rate than bare metal stents: 100, 85, and 70 % compared to
      75, 67, and 49 % at 3, 6, and 12 months (p < 0.01). CONCLUSION: The primary and
      secondary access patency rates after deployment of bare metal versus covered
      stents at the venous anastomosis were not significantly different. However, bare
      metal stents developed in-stent stenoses significantly sooner.

PMID- 22584755
TI  - Portal vein embolization: from evidence to expert opinion?

PMID- 22584756
TI  - Oncologic emergencies.
AB  - OBJECTIVES: To provide an up-to-date review of current literature on the
      pathophysiology, diagnosis, and management of five key malignancy-related
      complications: superior vena cava syndrome, malignant pericardial effusion,
      malignant spinal cord compression, hypercalcemia, and acute tumor lysis syndrome.
      DATA SOURCES: Database searches and review of relevant medical literature. DATA
      SYNTHESIS: Malignancy-related complications demand increased attention from
      intensivists due to their frequency and increasing cancer prevalence. Although
      such complications portend a poor prognosis, proper acute management can improve
      short-term outcomes by facilitating either definitive care of the underlying
      malignancy or the institution of appropriate palliative measures. CONCLUSIONS:
      Knowledge of malignancy-induced complications in critically ill patients
      expedites the ability of the intensivist to properly manage them. Five
      complications commonly requiring emergency management are addressed in this
      review. Specifically, superior vena cava syndrome may warrant radiation,
      chemotherapy, vascular stenting, or surgical resection. Malignant pericardial
      effusion may require emergency pericardiocentesis if cardiac tamponade develops.
      Malignant spinal cord compression demands immediate spinal imaging,
      glucocorticoids, and either surgery or radiation. Hypercalcemia requires
      aggressive intravenous hydration and a bisphosphonate. Acute tumor lysis syndrome
      necessitates intravenous hydration, rasburicase, and management of associated
      electrolyte abnormalities.

PMID- 22584757
TI  - Impact of an intensive care unit diary on psychological distress in patients and
      relatives*.
AB  - OBJECTIVE: To assess the impact of an intensive care unit diary on the
      psychological well-being of patients and relatives 3 and 12 months after
      intensive care unit discharge. DESIGN: Prospective single-center study with an
      intervention period between two control periods. SETTING: Medical-surgical
      intensive care unit in a 460-bed tertiary hospital. PATIENTS: Consecutive
      patients from May 2008 to November 2009 and their relatives. Study inclusion
      occurred after the fourth day in the intensive care unit. INTERVENTIONS: A diary
      written by both the patient's relatives and the intensive care unit staff.
      MEASUREMENTS AND MAIN RESULTS: Patients and relatives completed the Hospital
      Anxiety and Depression Scale and Peritraumatic Dissociative Experiences
      Questionnaire 3 months after intensive care unit discharge, and completed the
      Impact of Events Scale assessing posttraumatic stress-related symptoms 12 months
      after intensive care unit discharge. Of the 378 patients admitted during the
      study period, 143 were included (48 in the prediary period, 49 in the diary
      period, and 46 in the postdiary period). In relatives, severe posttraumatic
      stress-related symptoms after 12 months varied significantly across periods
      (prediary 80%, diary 31.7%, postdiary 67.6%; p<.0001). Similar results were
      obtained in the posttraumatic stress-related symptom score after 12 months in the
      surviving patients (prediary 34.6 +/- 15.9, diary 21 +/- 12.2, and postdiary 29.8
      +/- 15.9; p = .02). CONCLUSIONS: The intensive care unit diary significantly
      affected posttraumatic stress-related symptoms in relatives and surviving
      patients 12 months after intensive care unit discharge.

PMID- 22584758
TI  - Diagnostic accuracy of insulin-like growth factor binding protein-1 for amniotic
      fluid embolism*.
AB  - OBJECTIVE: To test whether serum insulin-like growth factor binding protein-1
      could be used as a biomarker of amniotic fluid passage into the maternal
      circulation. DESIGN: Case-control study. SETTING: Thirteen centers in France.
      PATIENTS: This case-control study included a group with amniotic fluid embolism
      (the amniotic fluid embolism group) and a group with symptoms unrelated to
      amniotic fluid embolism (the non-amniotic fluid embolism group). Serum insulin
      like growth factor binding protein-1 level was measured within 6 hrs from onset
      of symptoms. We also determined serum insulin-like growth factor binding protein
      1 in four additional groups of patients with 1) postpartum hemorrhage, 2)
      uncomplicated labor, 3) normal pregnancy, and 4) non-pregnant patients with acute
      pulmonary embolism. INTERVENTIONS: None. MEASUREMENTS: Serum insulin-like growth
      factor binding protein-1 levels were determined using an immuno-enzymatic assay.
      MAIN RESULTS: The amniotic fluid embolism group included 25 patients, the non
      amniotic fluid embolism group had 20 patients, the postpartum hemorrhage group
      had 24 patients, and the uncomplicated labor group had 50 patients. The serum
      levels of insulin-like growth factor binding protein-1 were higher in the
      amniotic fluid embolism group (234 134-635 umol/L) compared with the non-amniotic
      fluid embolism, postpartum hemorrhage, and uncomplicated labor groups, which had
      serum levels of 56 36-91 umol/L, 65 39-91 umol/L and 49 30-78 umol/L,
      respectively (p < .001). Serum insulin-like growth factor binding protein-1 level
      was not different in women during normal pregnancy (57 37-85 ug/L) compared to
      the uncomplicated labor group. Patients with acute pulmonary embolism had the
      lowest insulin-like growth factor binding protein-1 level (5 2-14 ug/L). The area
      under the receiver-operating-characteristic curve for serum insulin-like growth
      factor binding protein-1 was 0.98 0.97-1.00 for the amniotic fluid embolism
      diagnostic. Insulin-like growth factor binding protein-1 rose from 56 43-90 ug/L
      before symptoms to 458 161-1514 ug/L after the onset of symptoms in ten patients
      with available measurements of baseline serum insulin-like growth factor binding
      protein-1. CONCLUSION: Increased serum levels of insulin-like growth factor
      binding protein-1 appear to be a valuable biomarker of amniotic fluid passage
      into the maternal circulation and may be used to diagnose amniotic fluid
      embolism.

PMID- 22584759
TI  - Ultrasound assessment of lung aeration loss during a successful weaning trial
      predicts postextubation distress*.
AB  - OBJECTIVE: Postextubation distress after a successful spontaneous breathing trial
      is associated with increased morbidity and mortality. Predicting postextubation
      distress is therefore a major issue in critically ill patients. To assess whether
      lung derecruitment during spontaneous breathing trial assessed by lung ultrasound
      is predictive of postextubation distress. DESIGN AND SETTING: Prospective study
      in two multidisciplinary intensive care units within University Hospital.
      PATIENTS AND METHODS: One hundred patients were included in the study. Lung
      ultrasound, echocardiography, and plasma B-type natriuretic peptide levels were
      determined before and at the end of a 60-min spontaneous breathing trial and 4
      hrs after extubation. To quantify lung aeration, a lung ultrasound score was
      calculated. Patients were followed up to hospital discharge. MEASUREMENTS AND
      MAIN RESULTS: Fourteen patients failed the spontaneous breathing trial, 86 were
      extubated, 57 were definitively weaned (group 1), and 29 suffered from
      postextubation distress (group 2). Loss of lung aeration during the successful
      spontaneous breathing trial was observed only in group 2 patients: lung
      ultrasound scores increased from 15 [13;17] to 19 [16; 21] (p < .01). End
      spontaneous breathing trial lung ultrasound scores were significantly higher in
      group 2 than in group 1 patients: 19 [16;21] vs. 10 [7;13], respectively (p <
      .001) and predicted postextubation distress with an area under the receiver
      operating characteristic curve of 0.86. Although significantly higher in group 2,
      B-type natriuretic peptide and echocardiography cardiac filling pressures were
      not clinically helpful in predicting postextubation distress. CONCLUSION: Lung
      ultrasound determination of aeration changes during a successful spontaneous
      breathing trial may accurately predict postextubation distress.

PMID- 22584760
TI  - 1,25-Dihydroxyvitamin D fluctuations in cardiac surgery are related to age and
      clinical outcome*.
AB  - OBJECTIVE: To investigate the interrelationship between cardiac surgery, age,
      circulating concentrations of the vitamin D hormone 1,25-dihydroxyvitamin D, and
      clinical outcome. DESIGN: Prospective, monocentric, two-arm parallel study.
      SETTING: Tertiary Heart and Diabetes Center in the Federal State of North Rhine
      Westphalia, Germany. PATIENTS: Twenty-nine cardiac surgical patients aged <= 65
      yrs and 30 patients >= 75 yrs. MEASUREMENTS: We assessed 1,25-dihydroxyvitamin D
      and other biochemical parameters of mineral metabolism (calcium, phosphate, 25
      hydroxyvitamin D, and parathyroid hormone), various inflammatory markers (C
      reactive protein, interleukin-6 and 8), and different immunological parameters
      (CD4 and CD8 cells, monocyte HLA-DR expression). We collected blood samples
      preoperatively, immediately after surgery, and on postoperative days 1, 5, and
      30. In addition, we assessed adverse outcome until discharge as a composite of
      myocardial infarction, low cardiac output syndrome, infection, stroke, or in
      hospital death. RESULTS: There were significant transient cardiac surgery-related
      fluctuations in 1,25-dihydroxyvitamin D and the aforementioned parameters of
      mineral metabolism, inflammation, and immune status. Compared to younger
      patients, older patients had consistently lower 1,25-dihydroxyvitamin D and
      phosphate levels (p = .013 and p = .036, respectively) and significantly higher
      interleukin 6 and 8 levels (p = .008 and p < .001, respectively). Circulating
      1,25-dihydroxyvitamin D was directly related to glomerular filtration rate (R(2)
      = .227; p < .001) and inversely related to interleukin 6 (R(2) = .105; p = .012).
      The rate of adverse outcome tended to be higher in older than in younger patients
      (20.0% vs. 3.5%; p = .081). In risk score-adjusted logistic regression analysis,
      adverse outcome risk decreased by 7.7% (SE: 3.7%) for each pmol/L increment in
      1,25-dihydroxyvitamin D (p = .037). CONCLUSIONS: Circulating 1,25
      dihydroxyvitamin D levels fluctuate in relation to cardiac surgery. Low 1,25
      dihydroxyvitamin D levels are associated with inflammatory processes and age
      related differences in clinical outcome. Future studies should determine whether
      therapies aimed at treating low 1,25-dihydroxyvitamin D levels can improve the
      outcome in older cardiac surgery patients.

PMID- 22584761
TI  - Treatment limitations at admission to intensive care units in Australia and New
      Zealand: prevalence, outcomes, and resource use*.
AB  - BACKGROUND: Previous studies have addressed patients in whom treatment is
      withheld or withdrawn after a period of intensive care unit management. However,
      no studies have investigated the epidemiology of patients with treatment
      limitations in place at the time of intensive care unit admission. OBJECTIVE: To
      report the epidemiology and outcome of patients with treatment limitations at
      intensive care unit admission and to identify characteristics associated with
      survival and discharge to home. DESIGN: Retrospective database study using data
      from the Australian and New Zealand Intensive Care Society Adult Patient
      Database. SETTING: Australian and New Zealand intensive care units. PATIENTS: One
      hundred eighty-seven thousand four hundred and one intensive care patients
      collected over a 3-yr period, 5,989 (3.2%) of whom had treatment limitations at
      admission to the intensive care unit. INTERVENTIONS: Retrospective database study
      with no interventions. Data collected included patient characteristics, length of
      stay, mortality, and discharge destination. Mean intensive care unit bed days
      were used as a surrogate for resource consumption. MEASUREMENTS AND MAIN RESULTS:
      Between January 1, 2007, and December 31, 2009, 5,989 (3.2%) patients were
      reported to the Australia and New Zealand Intensive Care Society Adult Patient
      Database who had treatment limitation orders at admission to intensive care unit.
      Mortality was 53% (95% confidence interval 51.7%-54.3%) compared with 9% (95%
      confidence interval 8.9%-9.1%) in patients admitted for full active management (p
      <= .001). Overall, 30% of patients with treatment limitations were discharged
      directly to their homes. Intensive care unit bed day usage was similar between
      the two groups. Within the treatment limitation group, younger patients, those
      with less comorbid diseases, less acute physiological disturbance, and those
      admitted following elective surgery, were more likely to survive and be
      discharged home. Admission diagnosis was an important determinant of outcome with
      intracranial or subarachnoid hemorrhage predicting a extremely high mortality.
      CONCLUSIONS: Patients with treatment limitations on intensive care unit admission
      comprise approximately 2,000 patients per year in Australia and New Zealand.
      Despite such limitations, almost half of these patients survive their hospital
      admission and a third return directly to their home.

PMID- 22584762
TI  - Catecholaminergic polymorphic ventricular tachycardia found in an adolescent
      after a methylenedioxymethamphetamine and marijuana-induced cardiac arrest.
AB  - OBJECTIVE: To illustrate the challenges of managing patients with acute,
      undiagnosed arrhythmias through a case that demonstrates a possible association
      between catecholaminergic polymorphic ventricular tachycardia, a genetically
      determined severe arrhythmia disorder that often presents as either syncope or
      sudden death, and 3,4-Methylenedioxymethamphetamine ("Ecstasy") combined with
      marijuana, which are often considered safe drugs by users. DESIGN: Case report.
      SETTING: Pediatric intensive care unit. PATIENT: A 15-yr-old male collapsed
      suddenly after ingesting an unknown substance and smoking marijuana. He was
      successfully resuscitated by first-responder chest compressions and rescue
      breaths along with a single 100-J shock by paramedics. He was intubated and
      transferred to a pediatric intensive care unit. Initial cardiac workup was
      negative but severe instability on vasopressors and a family history of
      intermittent palpitations and syncope in his brother raised suspicion for
      catecholaminergic polymorphic ventricular tachycardia. Identification of the
      unknown substance required coordination with a toxicology laboratory.
      INTERVENTIONS: The patient had extremely labile cardiovascular responses to
      vasopressors. On day 5, his blood pressure was stable and he was extubated. A
      full cardiac workup, including a catheterization (preadmission to pediatric
      intensive care unit), electrocardiogram, cardiac magnetic resonance imaging were
      done to screen out most structural arrythmogenic diseases. A specific genetic
      test for catecholaminergic polymorphic ventricular tachycardia was sent.
      MEASUREMENTS AND MAIN RESULTS: The patient's methylenedioxymethamphetamine blood
      level was 87 ng/mL approximately 12 hrs after ingestion. Given the 3-8 hr half
      life of methylenedioxymethamphetamine, it is likely that levels were toxic at the
      time of ingestion (>110 ng/mL). Marijuana may have provided a synergistic
      critical catecholamine release to trigger an arrhythmia. Genetic testing showed a
      ryanodine receptor-2 mutation that was consistent with catecholaminergic
      polymorphic ventricular tachycardia. CONCLUSIONS: While an initial cardiac workup
      for an acute, undiagnosed arrhythmia may be negative, family history may be a
      simple, essential component of patient management and disease diagnosis. This
      case demonstrates a possible association between methylenedioxymethamphetamine,
      marijuana, and catecholaminergic polymorphic ventricular tachycardia. All genetic
      and structural arrythmogenic disorders should be considered when working up a
      patient with presumed toxin-induced arrhythmias.

PMID- 22584763
TI  - Randomized trial of automated, electronic monitoring to facilitate early
      detection of sepsis in the intensive care unit*.
AB  - OBJECTIVE: To determine whether automated identification with physician
      notification of the systemic inflammatory response syndrome in medical intensive
      care unit patients expedites early administration of new antibiotics or
      improvement of other patient outcomes in patients with sepsis. DESIGN: : A
      prospective randomized, controlled, single center study. SETTING: Medical
      intensive care unit of an academic, tertiary care medical center. PATIENTS: Four
      hundred forty-two consecutive patients admitted over a 4-month period who met
      modified systemic inflammatory response syndrome criteria in a medical intensive
      care unit. INTERVENTION: Patients were randomized to monitoring by an electronic
      "Listening Application" to detect modified (systemic inflammatory response
      syndrome) criteria vs. usual care. The listening application notified physicians
      in real time when modified systemic inflammatory response syndrome criteria were
      detected, but did not provide management recommendations. MEASUREMENTS AND MAIN
      RESULTS: The median time to new antibiotics was similar between the intervention
      and usual care groups when comparing among all patients (6.0 hr vs. 6.1 hr, p =
      .95), patients with sepsis (5.3 hr vs. 5.1 hr; p = .90), patients on antibiotics
      at enrollment (5.2 hr vs. 7.0 hr, p = .27), or patients not on antibiotics at
      enrollment (5.2 hr vs. 5.1 hr, p = .85). The amount of fluid administered
      following detection of modified systemic inflammatory response syndrome criteria
      was similar between groups whether comparing all patients or only patients who
      were hypotensive at enrollment. Other clinical outcomes including intensive care
      unit length of stay, hospital length of stay, and mortality were not shown to be
      different between patients in the intervention and control groups. CONCLUSIONS:
      Realtime alerts of modified systemic inflammatory response syndrome criteria to
      physicians in one tertiary care medical intensive care unit were feasible and
      safe but did not influence measured therapeutic interventions for sepsis or
      significantly alter clinical outcomes.

PMID- 22584764
TI  - Derivation of a cardiac arrest prediction model using ward vital signs*.
AB  - OBJECTIVE: Rapid response team activation criteria were created using expert
      opinion and have demonstrated variable accuracy in previous studies. We developed
      a cardiac arrest risk triage score to predict cardiac arrest and compared it to
      the Modified Early Warning Score, a commonly cited rapid response team activation
      criterion. DESIGN: A retrospective cohort study. SETTING: An academic medical
      center in the United States. PATIENTS: All patients hospitalized from November
      2008 to January 2011 who had documented ward vital signs were included in the
      study. These patients were divided into three cohorts: patients who suffered a
      cardiac arrest on the wards, patients who had a ward to intensive care unit
      transfer, and patients who had neither of these outcomes (controls).
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Ward vital signs from
      admission until discharge, intensive care unit transfer, or ward cardiac arrest
      were extracted from the medical record. Multivariate logistic regression was used
      to predict cardiac arrest, and the cardiac arrest risk triage score was
      calculated using the regression coefficients. The model was validated by
      comparing its accuracy for detecting intensive care unit transfer to the Modified
      Early Warning Score. Each patient's maximum score prior to cardiac arrest,
      intensive care unit transfer, or discharge was used to compare the areas under
      the receiver operating characteristic curves between the two models. Eighty-eight
      cardiac arrest patients, 2,820 intensive care unit transfers, and 44,519 controls
      were included in the study. The cardiac arrest risk triage score more accurately
      predicted cardiac arrest than the Modified Early Warning Score (area under the
      receiver operating characteristic curve 0.84 vs. 0.76; p = .001). At a
      specificity of 89.9%, the cardiac arrest risk triage score had a sensitivity of
      53.4% compared to 47.7% for the Modified Early Warning Score. The cardiac arrest
      risk triage score also predicted intensive care unit transfer better than the
      Modified Early Warning Score (area under the receiver operating characteristic
      curve 0.71 vs. 0.67; p < .001). CONCLUSIONS: The cardiac arrest risk triage score
      is simpler and more accurately detected cardiac arrest and intensive care unit
      transfer than the Modified Early Warning Score. Implementation of this tool may
      decrease rapid response team resource utilization and provide a better
      opportunity to improve patient outcomes than the modified early warning score.

PMID- 22584765
TI  - The determinants of hospital mortality among patients with septic shock receiving
      appropriate initial antibiotic treatment*.
AB  - OBJECTIVE: To identify the determinants of hospital mortality among patients with
      septic shock receiving appropriate initial antibiotic treatment. DESIGN: A
      retrospective cohort study of hospitalized patients with blood culture positive
      septic shock (January 2002-December 2007). SETTING: Barnes-Jewish Hospital, a
      1,250-bed urban teaching hospital. PATIENTS: Four hundred thirty-six consecutive
      patients with septic shock and a positive blood culture. INTERVENTIONS: Data
      abstraction from computerized medical records. MEASUREMENTS AND MAIN RESULTS:
      Septic shock was associated with bloodstream infection due to Gram-negative
      bacteria (59.2%) and Gram-positive bacteria (40.8%). Two hundred twenty-four
      patients (51.4%) died during their hospitalization. The presence of infection
      attributed to antibiotic-resistant bacteria was similar for patients who survived
      and expired (22.6% vs. 20.1%; p = .516). Multivariate logistic regression
      analysis demonstrated that infection acquired in the intensive care unit
      (adjusted odds ratio 1.99; 95% confidence interval 1.52-2.60; p = .011) and
      increasing Acute Physiology and Chronic Health Evaluation II scores (one-point
      increments) (adjusted odds ratio 1.11; 95% confidence interval 1.09-1.14; p <
      .001) were independently associated with a greater risk of hospital mortality,
      whereas infection with methicillin-susceptible Staphylococcus aureus (adjusted
      odds ratio 0.32; 95% confidence interval 0.20-0.52; p = .017) was independently
      associated with a lower risk of hospital mortality. Patients infected with
      methicillin-susceptible Staphylococcus aureus infections were statistically
      younger and had lower Charlson comorbidity and Acute Physiology and Chronic
      Health Evaluation II scores compared to patients with non-methicillin-susceptible
      Staphylococcus aureus infections. CONCLUSIONS: Among patients with septic shock
      who receive appropriate initial antibiotic treatment, acquisition of infection in
      the intensive care unit and severity of illness appear to be the most important
      determinants of clinical outcome.

PMID- 22584767
TI  - Outcomes and predictors of difficulty with coronary sinus lead removal.
AB  - With increasing coronary sinus (CS) pacemaker leads for cardiac resynchronization
      therapy, the need to remove these leads has risen. The purpose of this study is
      to describe a single center's experience with CS lead removal and to attempt to
      identify predictors of difficulty with lead removal and complications. We
      reviewed all percutaneous endocardial CS lead removals performed at our
      institution through February 2010. Successful removal with traction alone was
      considered simple while complex extractions required traction devices and/or
      laser sheaths. Between December 1996 and February 2010, 125 CS leads were
      percutaneously removed >=1 week post-implantation from 115 patients. One attempt
      at CS lead extraction was unsuccessful. The average duration since implantation
      for the CS leads was 1.54 years (+/- .75 years, range 8 days to 8.24 years). The
      majority of the leads were removed by simple traction (n = 114, 91.2 %). The
      remainder were removed by femoral approach with snare (n = 3, 2.4 %), locking
      stylet (n = 2, 1.6 %), or locking stylet and laser sheath (n = 6, 4.8 %). Half of
      CS leads in place greater than 4 years required complex extraction (n = 7/14, 50
      %). CS complications (n = 11 patients, 8.8 %) included CS or tributary thrombosis
      (n = 7/102, 6.9 %) and CS dissection (n = 4/102, 3.9 %). Major non-CS
      complications (n = 2 patients, 1.6 %) included a cardiac tear requiring
      pericardiocentesis and thoracotomy (n = 1, 0.8 %) and subclavian vein tear
      requiring surgical repair (n = 1, 0.8 %). Minor non-CS complications (n = 9
      patients, 7.2 %) included a pneumothorax (n = 1, 0.8 %), hematoma (n = 2, 1.6 %),
      subclavian vein thrombosis (n = 3, x%), and blood transfusion (n = 5, 4.0 %). A
      longer duration since implantation and larger lead diameter were associated with
      complex versus simple removal (p < .0001 and p = .0009 respectively).
      Percutaneous CS lead removal is successful by simple traction alone in the vast
      majority of cases. CS leads in place greater than 4 years, however, often require
      complex extraction. Specific extraction techniques can be implemented when simple
      traction is unsuccessful without an appreciable increase in complications.

PMID- 22584768
TI  - New editorial policies of BJPT.

PMID- 22584766
TI  - The relationship between delirium duration, white matter integrity, and cognitive
      impairment in intensive care unit survivors as determined by diffusion tensor
      imaging: the VISIONS prospective cohort magnetic resonance imaging study*.
AB  - OBJECTIVE: Evidence is emerging that delirium duration is a predictor of long
      term cognitive impairment in intensive care unit survivors. Relationships between
      1) delirium duration and brain white matter integrity, and 2) white matter
      integrity and long-term cognitive impairment are poorly understood and could be
      explored using magnetic resonance imaging. DESIGN, SETTING, PATIENTS: A two
      center, prospective cohort study incorporating delirium monitoring, neuroimaging,
      and cognitive testing in intensive care unit survivors. MEASUREMENTS: Delirium
      was evaluated with the Confusion Assessment Method for the Intensive Care Unit
      and cognitive outcomes were tested at 3 and 12-month follow-up. Following the
      intensive care unit stay, fractional anisotropy, a measure of white matter
      integrity, was calculated quantitatively using diffusion tensor imaging with a 3
      T magnetic resonance imaging scanner at hospital discharge and 3-month follow-up.
      We examined associations between 1) delirium duration and fractional anisotropy
      and 2) fractional anisotropy and cognitive outcomes using linear regression
      adjusted for age and sepsis. RESULTS: A total of 47 patients with a median age of
      50 yrs completed the diffusion tensor imaging-magnetic resonance imaging
      protocol. Greater duration of delirium (3 vs. 0 days) was associated with lower
      fractional anisotropy (i.e., reduced fractional anisotropy = white matter
      disruption) in the genu (-0.02; p = .04) and splenium (-0.01; p = .02) of the
      corpus callosum and anterior limb of the internal capsule (-0.02; p =.01) at
      hospital discharge. These associations persisted at 3 months for the genu (-0.02;
      p =.02) and splenium (-0.01; p = .004). Lower fractional anisotropy in the
      anterior limb of internal capsule at discharge and in genu of corpus callosum at
      three months was associated with worse cognitive scores at 3 and 12 months.
      CONCLUSIONS: In this pilot investigation, delirium duration in the intensive care
      unit was associated with white matter disruption at both discharge and 3 months.
      Similarly, white matter disruption was associated with worse cognitive scores up
      to 12 months later. This hypothesis-generating investigation may help design
      future studies to explore these complex relationships in greater depth.

PMID- 22584769
TI  - Aging and work: a challenge for the rehabilitation schedule.
AB  - BACKGROUND: The rapid aging of the workforce has motivated the development of
      studies that seek to maintain good health conditions, work ability, autonomy and
      the social integration of workers. OBJECTIVES: To present the theoretical
      framework, available measurements and models for promoting work ability.
      DISCUSSION: In the field of rehabilitation, the sedimentation of the conceptual
      model of the ability to work has a normative role and may be useful for assessing
      whether a person has a temporary or permanent loss of capacity as well as for
      defining a specific rehabilitation program. The concept may further help
      determine different aspects, both internal and external to the person, that could
      result in improved or restored work ability. CONCLUSION: In order to enhance the
      available measurements, propose new interventions for promoting work ability and
      to further its use as an outcome measure in rehabilitation, it is necessary to
      assume that the predictors relate to the individuals, their work and their life
      outside of work in dynamic interactions that require analytical methods which
      account for the multidimensionality of the construct.

PMID- 22584770
TI  - Physical therapy intervention in women with urinary incontinence associated with
      pelvic organ prolapse.
AB  - BACKGROUND: Urinary incontinence (UI) is a prevalent condition that affects women
      of all ages. Pelvic organ prolapse in conjunction with UI is a common occurrence.
      OBJECTIVE: To assess the effect of pelvic prolapse on the outcome of physical
      therapy treatment for women with UI. METHODS: The study included 48 women aged
      between 35 and 78 years who underwent anamnesis and measurement of pelvic floor
      strength (bi-digital test and perineometry). The physical therapy intervention
      consisted of transvaginal electrical stimulation and pelvic floor exercise for up
      to 15 weekly sessions. RESULTS: The majority of the women had normal delivery and
      2.6+/-1.5 children (range=0-7). Pelvic prolapse was observed in 72.4% of the
      women who had normal delivery, in 100% of those who had cesarean section, and in
      77.8% of those who had both normal and cesarean deliveries. 48% of the women had
      mixed UI, 39.5% had stress UI, and 12.5% had urge UI. The duration of symptoms
      varied from 2 to 28 years (7.9+/-5.3). In the participants with and without
      prolapse, a significant difference was observed in the pre- and post-treatment
      comparisons for the pelvic floor muscles. The pre- and post-treatment
      perineometry showed a significant increase only in the women with prolapse
      (p=0.048). 87.5% of the participants became continent. CONCLUSIONS: The physical
      therapy treatment was effective in treating and/or curing the symptoms of UI,
      whether or not associated with pelvic prolapse, regardless of the clinical type
      of incontinence. Clinical Trial Registration (Brazilian Clinical Trial Registry):
      RBR-3p5s66.

PMID- 22584771
TI  - Correlation among the Visual Gait Assessment Scale, Edinburgh Visual Gait Scale
      and Observational Gait Scale in children with spastic diplegic cerebral palsy.
AB  - BACKGROUND: Gait disorders are very common in children with spastic diplegia
      cerebral palsy (CP). In order to improve the CP children's gait and to quantify
      the outcomes of this intervention it becomes essential to perform an instrumented
      analysis before and after the intervention. OBJECTIVES: To analyze the
      correlation among the Edinburgh Visual Gait Scale (EVGS), the Visual Gait
      Assessment Scale (VGAS) and the Observational Gait Scale (OGS). METHODS: Cross
      sectional study aiming to analyze the gait of 8 children with spastic diplegia CP
      with level I or II in the Gross Motor Function Classification System (GMFCS)
      through the EVGS, VGAS and OGS scales performed by 3 examiners. This study was
      approved by the Research Ethics Committee of the Universidade Estadual de
      Campinas (UNICAMP). Weighted Kappa scores were used to analyze the data
      considering a significance level of 5%. RESULTS: The intra-rater analyses showed
      a moderate to excellent agreement (k=0.41, 1.00) among the methods of the
      children's classification, being the comparison between VGAS and the EVGS scales
      presented the highest level of agreement, while the OGS scale presented a
      considerable disagreement in comparison with other scales. The inter-rater
      agreement showed to be predominantly high. CONCLUSIONS: The results provide
      evidence that the VGAS and the EVGS scales are more suitable for children's
      spastic diplegia CP gait assessment when compared to OGS.

PMID- 22584772
TI  - Muscular power training: a new perspective in physical therapy approach of
      Parkinson's disease.

PMID- 22584773
TI  - Evaluation of precision and accuracy assessment of different 3-D surface imaging
      systems for biomedical purposes.
AB  - Three-dimensional (3-D) surface imaging has gained clinical acceptance,
      especially in the field of cranio-maxillo-facial and plastic, reconstructive, and
      aesthetic surgery. Six scanners based on different scanning principles (Minolta
      Vivid 910(r), Polhemus FastSCANTM, GFM PRIMOS(r), GFM TopoCAM(r), Steinbichler
      Comet(r) Vario Zoom 250, 3dMD DSP 400(r)) were used to measure five sheep skulls
      of different sizes. In three areas with varying anatomical complexity (areas, 1 =
      high; 2 = moderate; 3 = low), 56 distances between 20 landmarks are defined on
      each skull. Manual measurement (MM), coordinate machine measurements (CMM) and
      computer tomography (CT) measurements were used to define a reference method for
      further precision and accuracy evaluation of different 3-D scanning systems. MM
      showed high correlation to CMM and CT measurements (both r = 0.987; p < 0.001)
      and served as the reference method. TopoCAM(r), Comet(r) and Vivid 910(r) showed
      highest measurement precision over all areas of complexity; Vivid 910(r), the
      Comet(r) and the DSP 400(r) demonstrated highest accuracy over all areas with
      Vivid 910(r) being most accurate in areas 1 and 3, and the DSP 400(r) most
      accurate in area 2. In accordance to the measured distance length, most 3-D
      devices present higher measurement precision and accuracy for large distances and
      lower degrees of precision and accuracy for short distances. In general, higher
      degrees of complexity are associated with lower 3-D assessment accuracy,
      suggesting that for optimal results, different types of scanners should be
      applied to specific clinical applications and medical problems according to their
      special construction designs and characteristics.

PMID- 22584774
TI  - Exploration of the relationships between regional grey matter atrophy and
      cognition in multiple sclerosis.
AB  - Cognitive impairment may result in significant disability in patients with
      Multiple Sclerosis (MS). Previous Magnetic Resonance Imaging (MRI) studies on
      cognition in MS were mainly based on measures of gross brain involvement. This
      study, using voxel-based morphometry (VBM), aims to investigate associations
      between the regional distribution of grey matter (GM) damage and cognitive
      performance in patients with MS. Eighteen MS patients underwent an extensive
      neuropsychological battery and MRI, including T2-weighted scans and T1-weighted
      volumes. A group of 18 healthy individuals were also investigated by MRI and
      served as controls for the VBM. A cross-sectional analysis was first performed,
      to assess the pattern of regional GM atrophy in MS patients. Then, the impact of
      regional GM damage on patients' neuropsychological performance was investigated
      by multiple regression analyses in the patient group. Correlations between global
      indexes of brain damage and neuropsychological measures were also assessed for
      comparison with previous literature. The comparison between MS patients and
      healthy controls revealed a widespread pattern of regional GM atrophy. Consistent
      with previous studies, associations were found between neuropsychological scores,
      and global brain atrophy and T2-lesion volumes. Critically, significant
      associations were found between scores on the Symbol Digit Modalities test and
      Long Delay Cued Recall on the California Verbal Learning Test, and regional GM
      volumes in well localized areas of the prefrontal, parietal, temporal, and
      insular cortex. This study confirms that global assessments of brain damage
      correlate with measures of cognitive impairment in MS. Interestingly, VBM
      contributes to clarify those brain regions that more likely determine the
      cognitive deficits observed in patients. These findings clarify the
      pathophysiology of cognitive impairment in MS, and propose measures which could
      be considered for longitudinal monitoring of patients. 

PMID- 22584775
TI  - Mapping changes of in vivo connectivity patterns in the human mediodorsal
      thalamus: correlations with higher cognitive and executive functions.
AB  - The mediodorsal thalamic nucleus is recognized as an association hub mediating
      interconnections with mainly the prefrontal cortex. Tracer studies in primates
      and in vivo diffusion tensor tractography findings in both humans and monkeys
      confirm its role in relaying networks that connect to the dorsolateral
      prefrontal, orbitofrontal, frontal medial and cingulate cortex. Our study was
      designed to use in vivo probabilistic tractography to describe the pathways
      emerging from or projecting to the mediodorsal nucleus; moreover, to use such
      information to automatically define subdivisions based on the divergence of
      remote structural connections. Diffusion tensor MR imaging data of 156 subjects
      were utilized to perform connectivity-based segmentation of the mediodorsal
      nucleus by employing a k-means clustering algorithm. Two domains were revealed
      (medial and lateral) that are separated from each other by a sagittally oriented
      plane. For each subject, general assessment of cognitive performance by means of
      the Wechsler Abbreviated Scale of Intelligence and measures of Delis-Kaplan
      Executive Function System (D-KEFS) test was utilized. Inter-subject variability
      in terms of connectivity-based cluster sizes was discovered and the relative
      sizes of the lateral mediodorsal domain correlated with the individuals'
      performance in the D-KEFS Sorting test (r = 0.232, p = 0.004). Our results show
      that the connectivity-based parcellation technique applied to the mediodorsal
      thalamic nucleus delivers a single subject level descriptor of connectional
      topography; furthermore, we revealed a possible weak interaction between
      executive performance and the size of the thalamic area from which pathways
      converge to the lateral prefrontal cortex.

PMID- 22584776
TI  - Predictive value of interleukin-5 and monocyte chemotactic protein-1 for
      bacteremia in children with febrile neutropenia.
AB  - A variety of clinical and laboratory parameters have been used to predict
      bacteremia. We hypothesize that the generation of a cytokine profile could be
      used to identify patients at higher risk of bacteremia at the time of
      presentation with febrile neutropenia. We prospectively evaluated children with
      cancer who presented with an episode of febrile neutropenia. A multiplexed flow
      cytometric assay was performed which measured 15 cytokines and chemokines
      obtained before the initiation of antibiotics. Fifty-eight episodes of
      chemotherapy-induced febrile neutropenia were included in this study during which
      4 patients (7%) had bacteremia. An interleukin-5 level of >8 pg/dL had a
      sensitivity of 67% and a specificity of 96% to predict bacteremia. An monocyte
      chemotactic protein-1 level >1650 pg/dL had a sensitivity of 80% and a
      specificity of 82% to predict bacteremia. Erythrocyte sedimentation rate, C
      reactive protein, protein C, and other cytokines/chemokines were not predictive
      of bacteremia. Elevations of interleukin-5 and monocyte chemotactic protein-1 are
      predictive of bacteremia in children with cancer who have febrile neutropenia.
      Prospective studies should be undertaken to determine whether these parameters
      retain predictive value in a larger series of patients and can select children
      for outpatient management or early discharge.

PMID- 22584778
TI  - ABT-751 in relapsed childhood acute lymphoblastic leukemia.

PMID- 22584779
TI  - Necrotizing fasciitis caused by Serratia marcescens after venous access port
      implantation in a child with acute lymphoblastic leukemia.
AB  - Necrotizing fasciitis is a potentially life-threatening infection of deep skin
      layers and subcutaneous tissues that can easily spread across the fascia plate
      and is usually the result of a combined infection with anaerobic and aerobic
      microorganisms. The patient typically complains of excruciating pain, which is
      not necessarily in accordance with clinical signs. Early recognition of the
      condition is very important, and aggressive treatment with a combination of
      antibiotics and surgical procedure is crucial. We present a case of a 15-year-old
      girl with acute lymphoblastic leukemia who developed necrotizing fasciitis after
      venous access port implantation during induction chemotherapy.

PMID- 22584777
TI  - Cardiac failure 30 years after treatment containing anthracycline for childhood
      acute lymphoblastic leukemia.
AB  - In 1977, a 5-year-old girl diagnosed with acute lymphoblastic leukemia was
      treated on Dana-Farber Cancer Institute Childhood Acute Lymphoblastic Leukemia
      Protocol 77-01, receiving a cumulative doxorubicin dose of 465 mg/m(2), cranial
      radiation, and other drugs. After being in continuous complete remission for 34
      months, she developed heart failure and was treated with digoxin and furosemide.
      At 16 years of age, she was diagnosed and treated for dilated cardiomyopathy.
      Over the years, she continued to have bouts of heart failure, which became less
      responsive to treatment. At 36 years of age, she received a heart transplant. Six
      months later, she stopped taking her medications and suffered a sudden cardiac
      death.

PMID- 22584780
TI  - Systemic mastocytosis associated with childhood acute myeloid leukemia.

PMID- 22584781
TI  - Effect of recombinant human growth hormone (rhGH) on hemoglobin concentration in
      children with idiopathic growth hormone deficiency-related anemia.
AB  - Normocytic-normochromic anemia (NC/NC) has been attributed to impaired bone
      marrow erythropoiesis in growth hormone (GH)-deficient patients. Moreover, the
      GH/insulin-like growth factor-1 (IGF-1) axis has been implicated in
      erythropoiesis regulation. In this retrospective multicenter study, we evaluated
      the incidence of NC/NC anemia in 279 children (196 boys), median age 10.52 years,
      with isolated idiopathic GH deficiency, and the effect of recombinant human
      growth hormone (rhGH) therapy on hemoglobin levels. At 6-month intervals, we
      recorded the Hb standard deviation score (Hb-SDS), the IGF-1-SDS, weight, height,
      and pubertal stage. Forty-one boys and 7 girls had NC/NC anemia before starting
      substitutive therapy (-2.59 SD). The Hb-SDS was significantly increased (P<0.05)
      after 12 months of rhGH therapy. The effect of rhGH continued up to 48 months (
      0.39 SD), at which point all children had normal hemoglobin values. In
      conclusion, rhGH therapy resulted in normal hemoglobin values in all children
      enrolled in the study. These data support the concept that the GH/IGF-1 axis
      promotes erythropoiesis in vivo.

PMID- 22584782
TI  - Selective ophthalmic arterial infusion of chemotherapeutic drugs for recurrent
      retinoblastoma.
AB  - Introduced in 1988 by Kaneko and colleagues, selective ophthalmic arterial
      infusion of chemotherapeutic drug has recently gained more interest among
      retinoblastoma experts worldwide. The report showed that the procedure could be
      repeated up to 12 treatments without serious side effects. We report a 4-year-old
      girl with bilateral retinoblastoma. The left eye was enucleated for the group E
      disease. The right eye started with 3 retinal tumors (group C) was treated with
      systemic chemotherapy plus local therapy. Seven months after the last cycle of
      chemotherapy, the tumor recurred close to the fovea. Systemic chemotherapy was
      reinitiated without success. To avoid aggressive cryotherapy and external-beam
      radiotherapy, selective ophthalmic arterial infusion of chemotherapeutic drugs
      was performed for 15 sessions. The tumor responded partially without evidence of
      drug-induced retinal toxicity by the electroretinogram. Minor irregularities of
      the inner wall of supraclinoid portion of the internal carotid artery were
      observed only at the sixth session. Narrowing of the vascular lumen occurred on
      the last 2 sessions. We demonstrate that this technique when performed repeatedly
      could result in the anatomic changes of the small blood vessel. Careful follow-up
      is necessary for early detection of any serious consequences.

PMID- 22584783
TI  - Single-session biofeedback-assisted relaxation training in children with sickle
      cell disease.
AB  - Sickle cell disease (SCD) pain remains difficult to manage. This pilot study
      evaluated single-session biofeedback-assisted relaxation training (BART) for SCD
      pain in children. Ten participants (mean = 12.1 y) completed a 1-hour BART
      session using thermal biofeedback and home practice. Participants demonstrated
      changes in peripheral body temperature after the training session (d = 1.08) and
      at 6-week follow-up (d = 0.97) relative to their baseline visit. Reductions in
      patient-reported pain frequency were found after completing BART. Health-related
      quality of life and pain-related disability improvements were observed; however,
      effect sizes were small to minimal. Single-session BART may be a promising,
      complementary approach to medical management of pediatric SCD pain.

PMID- 22584784
TI  - Clinical analysis of childhood pancreatoblastoma arising from the tail of the
      pancreas.
AB  - Pancreatoblastoma is a rare pancreatic tumor. In this study, 3 cases of childhood
      pancreatoblastoma that arise from the tail of the pancreas were reported.
      Abdominal pain and vomiting were observed in 1 case considering the huge size of
      the tumor. The other 2 patients, who were previously well, complained of a mass
      in the abdomen after a casual physical examination. Elevated serum alpha
      fetoprotein levels were noted in all cases. Imaging findings indicated a well
      defined heterogeneous large mass in the left retroperitoneal space. Exploratory
      laparotomy revealed a large mass, arising from the tail of the pancreas. Surgery
      alone with complete excision of the masses was performed. Immunohistochemical
      staining showed that only alpha-fetoprotein was positive in all cases. All of
      these 3 cases have a good outcome in the follow-up without adjuvant chemotherapy.
      These data suggest that the diagnosis of pancreatoblastoma is difficult and
      should be suspected at palpation of an abdominal mass. alpha-Fetoprotein may
      serve as a tumor marker for preoperative diagnosis and postoperative recurrence.
      Pancreatoblastoma arising from the tail of the pancreas is a curable tumor, and
      adjuvant chemotherapy may not be necessary if the tumor can be excised
      completely.

PMID- 22584785
TI  - Pleuropulmonary blastoma: a single-institution experience.
AB  - Pleuropulmonary blastoma (PPB) is a rare primary intrathoracic mesenchymal
      malignancy that occurs exclusively in early childhood. Twelve patients were
      diagnosed with PPB (1 type I, 5 type II, and 6 type III) between 1979 and 2009 at
      our institution. Upfront complete tumor resection was successful in 5 of 6
      patients. Six patients had biopsy followed by neoadjuvant chemotherapy, 2 had
      complete tumor resection, and 2 had microscopic residual disease after surgery.
      All patients received vincristine, dactinomycin, and cyclophosphamide
      chemotherapy. Eight received additional chemotherapy with doxorubicin, cisplatin,
      etoposide, or ifosfamide. Three patients received local irradiation. The 5-year
      event-free and overall survivals were 33% +/- 14% and 42% +/- 14%, respectively.
      Median time to progression was 8 months. Five of 9 patients with gross total
      resection survived, whereas all 3 with gross residual disease died. Three of 5
      survivors did not receive radiation. A high index of suspicion for PPB must be
      maintained in all patients diagnosed with intrathoracic sarcoma in early
      childhood. Gross total resection is necessary for cure, and selected patients do
      not require radiation therapy.

PMID- 22584786
TI  - Minimum significant ratio of selectivity ratios (MSRSR) and confidence in ratio
      of selectivity ratios (CRSR): quantitative measures for selectivity ratios
      obtained by screening assays.
AB  - Development of inhibitor compounds selective against undesirable targets is
      critical in drug discovery. Selectivity ratios for candidate compounds are
      evaluated by dividing potencies from two assays assessing the off-target and
      target. Because all potency measurements have underlying uncertainty,
      understanding error propagation is essential to interpreting selectivity data.
      Assay noise introduces ambiguity in the statistical significance of selectivity
      ratios, particularly at low replicate numbers when compounds are often
      prioritized for subsequent testing. The ability to differentiate potency results
      for any pair of compounds in one assay is evaluated using a metric called minimum
      significant ratio (MSR). Potency results of one compound tested in a pair of
      assays can be differentiated by the minimum significant selectivity ratio (MSSR).
      To differentiate selectivity ratios for any pair of compounds, we extend this
      concept by proposing two new parameters called the minimum significant ratio of
      selectivity ratios (MSRSR) and confidence in ratio of selectivity ratios (CRSR).
      Importantly, these tools can be used after a single selectivity measurement. We
      describe these methods and illustrate their usefulness using structure-activity
      relationship data from a Janus kinase inhibitor project, in which these tools
      informed a cogent retesting strategy and enabled rapid and objective decision
      making.

PMID- 22584788
TI  - Cellular and molecular mechanisms of diabetic glomerulopathy.
AB  - The epidemic of diabetic kidney disease is predicted to rise significantly in the
      next decade and will continue to represent the leading cause of end-stage renal
      failure. The interaction between metabolic and haemodynamic insults represents an
      important driver of the relentless decline in renal function that we observe in
      patients with diabetes. Studies have described different cellular
      pathophysiological mechanisms of diabetic glomerulopathy; increased oxidative
      stress appears to be the major alteration that drives the activation of many
      other cellular pathways which in turn will result in the phenotypic alterations
      seen in diabetic glomerulopathy. The glomerulus should be seen as a delicate
      network of cells that interact closely with one another in regulating the process
      of water and small solute filtration. In diabetes, this equilibrium is disrupted
      and its correction should aim at reinstating the balanced equilibrium as seen in
      physiology. Future therapeutic challenges will be represented by a tissue
      specific personalized 'ad hoc' therapeutical approach which will depend on
      patients' characteristic and stage/progression of disease.

PMID- 22584787
TI  - Fludarabine and cyclophosphamide in combination with alemtuzumab in patients with
      primary high-risk, relapsed or refractory chronic lymphocytic leukemia.

PMID- 22584789
TI  - Urine albumin:protein ratio as a predictor of patient outcomes in CKD.

PMID- 22584790
TI  - HIV-associated nephropathy: a diagnosis in evolution.
AB  - HIV-1 associated nephropathy (HIVAN) is a clinical and renal histological disease
      characterized by the presence of heavy proteinuria associated with focal
      segmental glomerulosclerosis and microcystic tubular dilatation. These renal
      lesions lead to renal enlargement and rapid progression to kidney failure. People
      from African ancestry show a unique susceptibility to develop HIVAN. The study by
      Wearne and colleagues, which includes the largest group of patients of African
      ancestry with HIVAN studied so far, describes a novel renal histological variant
      of HIVAN, and suggests that antiretroviral therapies improve the clinical outcome
      of all HIV-associated renal diseases. These findings, when interpreted in the
      context of recent advances in our understanding of the molecular pathogenesis and
      genetics of HIVAN, will facilitate the recognition of all clinical variants of
      HIVAN as well the planning of better screening, prevention, and treatment
      programs for all HIV nephropathies.

PMID- 22584791
TI  - Clinical features and management of parastomal pyoderma gangrenosum in
      inflammatory bowel disease.
AB  - BACKGROUND: Pyoderma gangrenosum (PG) is often associated with inflammatory bowel
      disease even after bowel surgery, but it remains an extremely rare pathology. The
      purpose of this study was to investigate the clinical features and treatment of
      PG and to consider proper management for peristomal PG. METHODS: Demographic data
      for patients who underwent colorectal surgery with ostomy creation at Hyogo
      College of Medicine between July 2007 and July 2011 were prospectively collected.
      The main outcome measures were postoperative occurrence of peristomal PG by type:
      explosive and rapidly spreading type (type R) and indolent and gradually
      spreading type (type G). RESULTS: Overall prevalence was 11/738 (1.5%), with type
      R in 5 patients and type G in 6. Type R and type G were significantly more common
      in ulcerative colitis and Crohn's disease, respectively (p = 0.01). Type R
      developed within 6 days after surgery. Type G developed a mean of 52 days after
      surgery. Complete healing required a long time in both types, with means of 69
      days for type R and 48 days for type G. CONCLUSION: Although peristomal PG was a
      rare complication after surgery, differences in the development of PG were
      observed between ulcerative colitis and Crohn's disease. Careful observation and
      knowledge of PG are needed.

PMID- 22584792
TI  - Tumor markers in clinical practice: a review focusing on common solid cancers.
AB  - Tumor markers are playing an increasingly important role in cancer detection and
      management. These laboratory-based tests are potentially useful in screening for
      early malignancy, aiding cancer diagnosis, determining prognosis, surveillance
      following curative surgery for cancer, up front predicting drug response or
      resistance, and monitoring therapy in advanced disease. Clinically useful markers
      include fecal occult blood testing in screening for early colorectal cancer,
      carcinoembryonic antigen in the management of patients with colorectal cancer,
      both alpha-fetoprotein and human chorionic gonadotrophin in the management of
      patients with non-seminomatous germ cell tumors, CA 125 for monitoring therapy in
      patients with ovarian cancer, estrogen receptors for predicting response to
      hormone therapy in breast cancer, human epidermal growth factor receptor 2 for
      the identification of women with breast cancer likely to respond to trastuzumab
      (Herceptin) and KRAS mutational status for identifying patients with advanced
      colorectal cancer likely to benefit from treatment with the anti-epidermal growth
      factor receptor antibodies, cetuximab and panitumumab. Although widely used, the
      value of prostate-specific antigen screening in reducing mortality from prostate
      cancer is unclear.

PMID- 22584794
TI  - Calibration strategies to validate predictive models: is new always better?

PMID- 22584795
TI  - Septic shock and chemotherapy-induced cytopenia: effects on microcirculation.
AB  - PURPOSE: Neutrophil and platelet activation and their interactions with
      endothelial cells are considered central features of sepsis-induced
      microcirculatory alterations. However, no study has evaluated the microvascular
      pattern of septic shock patients with chemotherapy-induced severe cytopenia.
      METHODS: Demographic and hemodynamic variables together with sublingual
      microcirculation recording [orthogonal polarization spectral imaging enhanced by
      sidestream dark-field technology (OPS-SDF) videomicroscopy] were collected in
      four groups of subjects: septic shock (SS, N = 9), septic shock in cytopenic
      patients (NSS, N = 8), cytopenia without infection (NEUTR, N = 7), and healthy
      controls (CTRL, N = 13). Except for controls, all measurements were repeated
      after complete resolution of septic shock and/or neutropenia. Video files were
      processed using appropriate software tool and semiquantitatively evaluated [total
      vascular density (TVD, mm/mm(2)), perfused vessel density (PVD, mm/mm(2)),
      proportion of perfused vessels (PPV, %), mean flow index (MFI), and flow
      heterogeneity index (FHI)]. RESULTS: Compared with controls, there were
      statistically significant microcirculatory alterations within all tested groups
      of patients (TVD: SS = 8.8, NSS = 8.8, NEUTR = 9.1 versus CTRL = 12.6, p < 0.001;
      PVD: SS = 6.3, NSS = 6.1, NEUTR = 6.9 versus CTRL = 12.5, p < 0.001; PPV: SS =
      71.6, NSS = 68.9, NEUTR = 73.3 versus CTRL = 98.7, p < 0.001; MFI: SS = 2.1, NSS
      = 1.9, NEUTR = 2.1 versus CTRL = 3.0, p < 0.05; FHI: SS = 1.0, NSS = 0.9, NEUTR =
      0.6 versus CTRL = 0.0, p < 0.001). No significant differences were detected
      between SS, NSS, and NEUTR groups at baseline. Incomplete restoration of
      microcirculatory perfusion was observed after septic shock and/or neutropenia
      resolution with a trend towards better recovery in MFI and FHI variables in NSS
      as compared with SS patients. CONCLUSIONS: Microvascular derangements in septic
      shock did not differ between noncytopenic and cytopenic patients. Our data might
      suggest that profound neutropenia and thrombocytopenia do not render
      microcirculation more resistant to sepsis-induced microvascular alterations. The
      role and mechanisms of microvascular alterations associated with chemotherapy
      induced cytopenia warrant further investigation.

PMID- 22584793
TI  - Comparison between SAPS II and SAPS 3 in predicting hospital mortality in a
      cohort of 103 Italian ICUs. Is new always better?
AB  - PURPOSE: More recent severity scores should be more reliable than older ones
      because they account for the improvement in medical care over time. To provide
      more insight into this issue, we compared the predictive ability of the
      Simplified Acute Physiology Score (SAPS) II and SAPS 3 (originally developed from
      data collected in 1991-1992 and 2002, respectively) on a sample of critically ill
      patients. METHODS: This was a prospective observational study on 3,661 patients
      from 103 Italian intensive care units. Standardized mortality ratios (SMRs) were
      calculated. Assessment of calibration across risk classes was performed using the
      GiViTI calibration belt. Discrimination was evaluated by means of the area under
      the receiver operating characteristic analysis. RESULTS: Both scores were shown
      to discriminate fairly. SAPS 3 largely overpredicted mortality, more than SAPS II
      (SMR 0.63, 95 % CI 0.60-0.66 vs. 0.87, 95 % CI 0.83-0.91). This result was
      consistent and statistically significant across all risk classes for SAPS 3. SAPS
      II did not show relevant deviations from ideal calibration in the first two
      deciles of risk, whereas in higher-risk classes it overpredicted mortality.
      CONCLUSIONS: Both scores provided unreliable predictions, but unexpectedly the
      newer SAPS 3 turned out to overpredict mortality more than the older SAPS II.

PMID- 22584796
TI  - Gluco- and mineralocorticoid biological effects of a 7-day treatment with low
      doses of hydrocortisone and fludrocortisone in septic shock.
AB  - PURPOSE: The benefits of low-dose steroids in septic shock remain controversial.
      We investigated if these low doses were able to induce their expected hormonal
      effects by analyzing the biological modifications observed during the study,
      which first demonstrated the survival benefit of low-dose steroids. METHODS: This
      was a multicenter, placebo-controlled, randomized, double-blind study in which
      299 septic shock patients received a 7-day treatment with a combination of
      hydrocortisone (50 mg intravenously four times daily) and fludrocortisone (50 MUg
      orally once daily) or matching placebos. Gluco- and mineralocorticoid biological
      effects observed during the 7 days of treatment were compared between groups.
      RESULTS: Steroids significantly decreased eosinophil counts from day 2 to day 7.
      Steroids significantly increased plasma glucose from day 2 (compared with
      placebos: +0.8 mmol/l) to day 7 (+1.8 mmol/l) and cholesterol from day 3 (+0.54
      mmol/l) to day 7 (+0.39 mmol/l). Steroids significantly increased plasma sodium
      from day 3 (+2 mmol/l) to day 7 (+5 mmol/l) and significantly decreased plasma
      potassium on day 7 (-0.2 mmol/l). Steroids significantly decreased urinary
      sodium/potassium ratio from day 2 (-47 %) to day 7 (-57 %) and sodium fractional
      excretion from day 3 (-25 %) to day 7 (-66 %). Steroids significantly increased
      urine output on day 4 and 5 and osmolar clearance from day 4 to day 7, and
      decreased free-water clearance from day 4 to day 7, this effect being significant
      on day 4 and 6. CONCLUSIONS: In septic shock, low-dose steroids induced both
      gluco- and mineralocorticoid biological effects and seemed to improve renal
      function. Most of these effects appeared after 2-3 days of treatment and lasted
      at least until the end of treatment.

PMID- 22584797
TI  - Estimation of mean systemic filling pressure in postoperative cardiac surgery
      patients with three methods.
AB  - PURPOSE: To assess the level of agreement between different bedside estimates of
      effective circulating blood volume-mean systemic filling pressure (Pmsf), arm
      equilibrium pressure (Parm) and model analog (Pmsa)-in ICU patients. METHODS:
      Eleven mechanically ventilated postoperative cardiac surgery patients were
      studied. Sequential measures were made in the supine position, rotating the bed
      to a 30 degrees  head-up tilt and after fluid loading (500 ml colloid). During
      each condition four inspiratory hold maneuvers were done to determine Pmsf; arm
      stop-flow was created by inflating a cuff around the upper arm for 30 s to
      measure Parm, and Pmsa was estimated from a Guytonian model of the systemic
      circulation. RESULTS: Mean Pmsf, Parm and Pmsa across all three states were 20.9
      +/- 5.6, 19.8 +/- 5.7 and 14.9 +/- 4.0 mmHg, respectively. Bland-Altman analysis
      for the difference between Parm and Pmsf showed a non-significant bias of -1.0 +/
      3.08 mmHg (p = 0.062), a coefficient of variation (COV) of 15 %, and limits of
      agreement (LOA) of -7.3 and 5.2 mmHg. For the difference between Pmsf and Pmsa we
      found a bias of -6.0 +/- 3.1 mmHg (p < 0.001), COV 17 % and LOA -12.4 and 0.3
      mmHg. Changes in Pmsf and Parm and in Pmsf and Pmsa were directionally concordant
      in response to head-up tilt and volume loading. CONCLUSIONS: Parm and Pmsf are
      interchangeable in mechanically ventilated postoperative cardiac surgery
      patients. Changes in effective circulatory volume are tracked well by changes in
      Parm and Pmsa.

PMID- 22584798
TI  - Assessment of patient-ventilator breath contribution during neurally adjusted
      ventilatory assist.
AB  - PURPOSE: During neurally adjusted ventilatory assist (NAVA), it is difficult to
      quantify the relative contribution of the patient versus the ventilator to the
      inspiratory tidal volume (Vt(insp)). To solve this problem, we developed an
      index, the "patient-ventilator breath contribution" (PVBC), using the inspiratory
      deflection of the diaphragmatic electrical activity (?EAdi) and Vt(insp) during
      assisted and non-assisted breaths. This study evaluated the PVBC index in an
      experimental setup. METHOD: Nine intubated and sedated rabbits were studied
      during repeated ramp increases of the NAVA level. One breath was non-assisted at
      each NAVA level. The PVBC index was evaluated during resistive loading and after
      acute lung injury. PVBC was calculated by relating Vt(insp)/?EAdi of a non
      assisted breath to that of the preceding assisted breath. The PVBC was compared
      to the relative contribution of esophageal pressure (?Pes) to transpulmonary
      pressure deflections (?P (L,dyn)). RESULTS: The relationship between PVBC and
      ?Pes/?P (L,dyn) was slightly curvilinear with an intercept different from zero (y
      = -1x (2 )+ 1.64x + 0.21) and a determination coefficient (R (2)) of 0.95.
      Squaring the PVBC values resulted in a near perfect linear relationship (y =
      1.02x + 0.05) between PVBC(2) and ?Pes/?P (L,dyn) with an R (2) of 0.97.
      CONCLUSION: This study shows that Vt(insp) and EAdi can be used to predict the
      contribution of the inspiratory muscles versus that of the ventilator during
      NAVA. If clinically applicable, this could serve to quantify and standardize the
      adjustment of the level of assist, and hence reduce the risks of excessive
      ventilatory assist. Further studies are required to evaluate if this method is
      clinically applicable.

PMID- 22584799
TI  - Clinical course and outcome for critically ill children with Down syndrome: a
      retrospective cohort study.
AB  - PURPOSE: Children with Down syndrome (DS) have several genetic anomalies within
      chromosome 21 which may influence their response to critical illness. We compared
      the intensive care course and outcome of children with DS versus those without.
      METHODS: Retrospective cohort study in four English paediatric intensive care
      units (ICUs) (2003-2009, n = 33,485). We examined, via a competing risks model,
      whether risk (subhazard) for ICU mortality differed for children with DS, after
      adjusting for important confounders. RESULTS: DS patients exhibited lower disease
      severity at ICU admission but subsequently required a higher proportion of
      cardiovascular support, and similar renal support to non-DS patients. Children
      with DS (n = 1,278) had lower crude mortality than those without (4.2 versus 6.2
      %, p = 0.003). This was not significant when expressed as standardized mortality
      ratio: 0.83 [95 % confidence interval (CI) 0.63-1.09] versus 0.90 (95 % CI 0.86
      0.94). However, the competing risks model showed that mortality risk was
      influenced by length of ICU stay. At admission, DS patients exhibited a subhazard
      for mortality of 0.63 (95 % CI 0.46-0.85), which increased to 1.00 by day 10 of
      admission, and continued rising above that of non-DS children thereafter.
      CONCLUSIONS: Children with DS require a higher proportion of organ support than
      expected by disease severity at ICU admission. In addition, the mortality risk
      for children with DS is dependent upon length of ICU stay. These findings could
      reflect differences in case mix, but are also compatible with different response
      to critical illness in this group.

PMID- 22584800
TI  - Anemia and brain oxygen after severe traumatic brain injury.
AB  - PURPOSE: To investigate the relationship between hemoglobin (Hgb) and brain
      tissue oxygen tension (PbtO(2)) after severe traumatic brain injury (TBI) and to
      examine its impact on outcome. METHODS: This was a retrospective analysis of a
      prospective cohort of severe TBI patients whose PbtO(2) was monitored. The
      relationship between Hgb-categorized into four quartiles (<=9; 9-10; 10.1-11; >11
      g/dl)-and PbtO(2) was analyzed using mixed-effects models. Anemia with
      compromised PbtO(2) was defined as episodes of Hgb <= 9 g/dl with simultaneous
      PbtO(2) < 20 mmHg. Outcome was assessed at 30 days using the Glasgow outcome
      score (GOS), dichotomized as favorable (GOS 4-5) vs. unfavorable (GOS 1-3).
      RESULTS: We analyzed 474 simultaneous Hgb and PbtO(2) samples from 80 patients
      (mean age 44 +/- 20 years, median GCS 4 (3-7)). Using Hgb > 11 g/dl as the
      reference level, and controlling for important physiologic covariates (CPP,
      PaO(2), PaCO(2)), Hgb <= 9 g/dl was the only Hgb level that was associated with
      lower PbtO(2) (coefficient -6.53 (95 % CI -9.13; -3.94), p < 0.001). Anemia with
      simultaneous PbtO(2) < 20 mmHg, but not anemia alone, increased the risk of
      unfavorable outcome (odds ratio 6.24 (95 % CI 1.61; 24.22), p = 0.008),
      controlling for age, GCS, Marshall CT grade, and APACHE II score. CONCLUSIONS: In
      this cohort of severe TBI patients whose PbtO(2) was monitored, a Hgb level no
      greater than 9 g/dl was associated with compromised PbtO(2). Anemia with
      simultaneous compromised PbtO(2), but not anemia alone, was a risk factor for
      unfavorable outcome, irrespective of injury severity.

PMID- 22584802
TI  - Lung ultrasound to avoid catastrophic care for false pneumothorax.

PMID- 22584801
TI  - Ordering CT pulmonary angiography to exclude pulmonary embolism: defense versus
      evidence in the emergency room.
AB  - PURPOSE: To identify reasons for ordering computed tomography pulmonary
      angiography (CTPA), to identify the frequency of reasons for CTPA reflecting
      defensive behavior and evidence-based behavior, and to identify the impact of
      defensive medicine and of training about diagnosing pulmonary embolism (PE) on
      positive results of CTPA. METHODS: Physicians in the emergency department of a
      tertiary care hospital completed a questionnaire before CTPA after being trained
      about diagnosing PE and completing questionnaires. RESULTS: Nine hundred patients
      received a CTPA during 3 years. For 328 CTPAs performed during the 1-year study
      period, 140 (43 %) questionnaires were completed. The most frequent reasons for
      ordering a CTPA were to confirm/rule out PE (93 %), elevated D-dimers (66 %),
      fear of missing PE (55 %), and Wells/simplified revised Geneva score (53 %). A
      positive answer for "fear of missing PE" was inversely associated with positive
      CTPA (OR 0.36, 95 % CI 0.14-0.92, p = 0.033), and "Wells/simplified revised
      Geneva score" was associated with positive CTPA (OR 3.28, 95 % CI 1.24-8.68, p =
      0.017). The proportion of positive CTPA was higher if a questionnaire was
      completed, compared to the 2-year comparison period (26.4 vs. 14.5 %, OR 2.12, 95
      % CI 1.36-3.29, p < 0.001). The proportion of positive CTPA was non-significantly
      higher during the study period than during the comparison period (19.2 vs. 14.5
      %, OR 1.40, 95 % CI 0.98-2.0, p = 0.067). CONCLUSION: Reasons for CTPA reflecting
      defensive behavior-such as "fear of missing PE"-were frequent, and were
      associated with a decreased odds of positive CTPA. Defensive behavior might be
      modifiable by training in using guidelines.

PMID- 22584803
TI  - Enhancement effect of two ecological earthworm species (Eisenia foetida and
      Amynthas robustus E. Perrier) on removal and degradation processes of soil DDT.
AB  - Effects of two ecological earthworm species (epigeic Eisenia foetida and endogeic
      Amynthas robustus E. Perrier) with different densities (15 and 30 individuals per
      kg of soil) on the removal of soil 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane
      (DDT) with two pollution levels (2 and 4 mg kg(-1)) were investigated.
      Concentrations of DDT and its metabolites, including 1,1-dichloro-2,2-bis(4
      chlorophenyl)ethane (DDD), 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (DDE),
      and 1-chloro-2,2-bis(4-chlorophenyl)ethylene (DDMU), were monitored after 60,
      180, and 360 days of incubation. The results obtained showed that both earthworm
      species can significantly enhance degradation of soil DDT to its metabolites. For
      E. foetida, the higher earthworm density showed significantly higher rate of DDT
      degradation than the lower one. Anaerobic reductive dechlorination was the main
      degradation pathway over 180 days of incubation, while the aerobic dechlorination
      process was promoted between 180 and 360 days of incubation. Some earthworm
      amended treatments showed significantly higher microbial biomass carbon and
      nitrogen than the control, which suggested that earthworms might enhance the
      microbial degradation of DDT. Both earthworm species would have the potential to
      be applied to enhance the remediation of agricultural lands polluted by DDT.

PMID- 22584804
TI  - The role of a mineralocorticoid receptor gene functional polymorphism in the
      symptom dimensions of persistent ADHD.
AB  - Attention-deficit/hyperactivity disorder (ADHD) affects approximately 5 % of
      school-aged children and 2.5 % of adults. Genetic studies in ADHD have pointed to
      genes in different neurobiological systems, with relatively small individual
      effects. The mineralocorticoid receptor is the main receptor involved in the
      initial triggering of stress response. Therefore, its encoding gene (NR3C2) is a
      candidate for psychiatric disorder studies, including ADHD, and behavioral
      phenotypes. There is evidence that the Val allele of the MRI180V polymorphism
      (rs5522) increases the risk of depression, attention and cognitive deficits. We
      investigated the possible role of the mineralocorticoid receptor gene in the
      symptom dimensions and susceptibility to persistent ADHD. We compared genotype
      and allele frequencies in 478 adult patients with ADHD and 597 controls and
      symptom dimensions in 449 patients and 132 controls. Diagnoses were based on the
      DSM-IV criteria. ADHD symptom dimensions were investigated with SNAP-IV for ADHD
      severity and Barkley scales for severity and impairment. Carriers of the Val
      allele presented higher inattention, hyperactivity/impulsivity and impairment
      scores, while genotype and allele frequencies did not differ between patients and
      controls. These results are consistent with a possible link between genetic
      variations in the HPA axis and inattention and hyperactivity measures.

PMID- 22584805
TI  - Single-subject classification of schizophrenia using event-related potentials
      obtained during auditory and visual oddball paradigms.
AB  - In the search for the biomarkers of schizophrenia, event-related potential (ERP)
      deficits obtained by applying the classic oddball paradigm are among the most
      consistent findings. However, the single-subject classification rate based on
      these parameters remains to be determined. Here, we present a data-driven
      approach by applying machine learning classifiers to relevant oddball ERPs.
      Twenty-four schizophrenic patients and 24 matched healthy controls finished
      auditory and visual oddball tasks while high-density electrophysiological
      recordings were applied. The N1 component in response to standards and target as
      well as the P3 component following targets were submitted to different machine
      learning algorithms and the resulting ERP features were submitted to further
      correlation analyses. We obtained a classification accuracy of 72.4 % using only
      two ERP components. Latencies of parietal N1 components to visual standard
      stimuli at electrode positions Pz and P1 were sufficient for classification.
      Further analysis revealed a high correlation of these features in controls and an
      intermediate correlation in schizophrenia patients. These data exemplarily show
      how automated inference may be applied to classify a pathological state in single
      subjects without prior knowledge of their diagnoses and illustrate the potential
      of machine learning algorithms for the identification of potential biomarkers.
      Moreover, this approach assesses the discriminative accuracy of one of the most
      consistent findings in schizophrenia research by means of single-subject
      classification.

PMID- 22584806
TI  - Chemokines in bipolar disorder: trait or state?
AB  - Recent evidence has suggested that inflammatory and immune mechanisms may play a
      role in the pathophysiology of bipolar disorder (BD). Only a few studies have
      assessed the profile of chemokines, a family of chemotactic cytokines related to
      the recruitment of leukocytes, in BD. The objective of our study was to evaluate
      the plasma levels of chemokines in BD patients in different mood states in
      comparison with healthy controls. Seventy BD type I patients (35 in euthymia and
      35 in mania), and 50 healthy controls matched by age, gender, and education level
      were enrolled in this study. All subjects were assessed by the Mini-International
      Neuropsychiatry Interview and the patients by the Young Mania Rating Scale and
      the Hamilton Depression Rating Scale. The plasma levels of CCL2, CCL3, CCL11,
      CCL24, CXCL8, and CXCL10 were measured by enzyme-linked immunosorbent assay. BD
      patients presented higher plasma levels of CCL11 (1.69-fold increase; p < 0.001),
      CCL24 (1.40-fold increase; p = 0.02), CXCL10 (1.45-fold increase; p < 0.001) and
      decreased plasma levels of CXCL8 (8.68-fold decrease p < 0.001). Logistic
      regression stressed the main effect of increased plasma levels of CXCL10 (OR =
      1.009, 95 % CI = 1.000-1.018, p = 0.042) and CCL11 (OR = 1.002, 95 % CI = 1.001
      1.003, p = 0.003) and decreased plasma levels of CXCL8 (OR = 0.995, 95 % CI =
      0.990-0.999, p = 0.013) to BD. This study reinforces the view that BD is
      associated with an immune dysfunction.

PMID- 22584808
TI  - [Challenges of the treatment of patients with gestational trophoblastic disease].

PMID- 22584807
TI  - Double innervation of the brachialis muscle: anatomic-physiological study.
AB  - INTRODUCTION: Double innervation of the brachialis muscle has been previously
      reported in anatomical studies. This study aims to investigate the frequency and
      clinical significance of double innervation of brachialis by anatomical and
      electromyographic techniques. MATERIALS AND METHODS: (1) The existence, origin
      and pattern of distribution of a branch from the radial nerve to brachialis were
      dissected on 20 cadaveric arms. (2) Nerve conduction studies (NCS) of 100
      patients were performed. The radial nerve was stimulated, registering muscle
      potentials (MP) in the brachialis muscle. Subsequently, another MP was obtained
      by Erb's stimulation, corresponding to the whole brachialis innervation. The
      relative percentage of innervation from the radial nerve was calculated. (3) Two
      patients with lesions of the lateral cord of the brachial plexus and preserved
      elbow flexion were submitted to NCS. RESULTS: Double innervation was found in 65
      % of the anatomical preparations, following different patterns of distribution.
      In the NCS, 90% of the patients showed MP in the brachialis muscle after
      stimulating the radial nerve. The mean percentage of relative innervation was 11
      %. Two patients with lesions of the lateral cord showed an important contribution
      from the radial nerve. CONCLUSIONS: Variations in the relative percentage of
      innervation from the radial nerve could be due to the different sizes and shapes
      of this branch. The functional significance of this branch can become crucial if
      the main innervation to the brachialis muscle fails. When planning surgical
      antero-external approach to the humerus, it should be kept in mind and preserved.

PMID- 22584809
TI  - [Self-reported adherence to prescribed medicines during pregnancy].
AB  - PURPOSE: To assess medication adherence therapeutic during pregnancy in a sample
      of Brazilian women during the post-partum period. METHODS: We conducted a cross
      sectional study in the obstetric unit of a university hospital, Brazil, between
      August and November 2010. We recruited patients aged 18 years or more, with a
      gestational age of more than 22 weeks whose newborns weighed more than 500 g.
      Patients were excluded if they used sedatives or other mind-altering drugs. Data
      were collected after labor using a structured questionnaire containing questions
      about sociodemographic characteristics, medication use, number of previous
      pregnancies, contraceptive methods, prenatal care, and medication adherence.
      Medication adherence was assessed using the four-item Morisky medication
      adherence scale - MMAS-4, groups were compared by the Fisher exact Test and
      Kruskal-Wallis Test and Chi2 de Pearson Test. RESULTS: Mean age was 22.5 years
      (SD=6.5), and 53.8% of the pregnant women had initiated prenatal care during the
      first trimester of pregnancy. Of the 130 patients interviewed, 96.9% had used at
      least one prescribed drug during pregnancy, with an average of 2.8 drugs per
      patient. The major classes prescribed were antianemics (55.1%), analgesics, anti
      inflammatories, and antipyretics (19.0%) and anti-infectives (7.2%). 71.6% took
      two to four drugs. Only 19.2% of patients were considered adherent. The variables
      that showed a negative influence on adherence were: higher level of education,
      having one's own income, earlier prenatal care and previous abortion. CONCLUSION:
      Our findings indicate that, although most of the patients used prescribed drugs
      during pregnancy, the rate of medication adherence was low, which indicates the
      need for further investigation about the impact of non-adherence during pregnancy
      and its causes.

PMID- 22584810
TI  - [Influence of maternal and fetal intercurrences on the different degrees of
      chorioamnionitis].
AB  - PURPOSE: To evaluate the influence of maternal complications, prematurity, fetal
      anthropometric parameters and conditions of the newborn on different degrees of
      chorioamnionitis. METHODS: We analyzed 90 placentas from deliveries performed at
      the General Hospital of Triangulo Mineiro Federal University with a diagnosis of
      inflammation in the anatomopathological exams. We reviewed the medical records to
      obtain relevant maternal and fetal information. The infections were classified as
      grade I - deciduitis; grade II - chorioamnionitis; grade III - chorioamnionitis
      and vasculitis; grade IV - neonatal sepsis and grade V - fetal death and
      pneumonitis. RESULTS: Among the pregnant women analyzed, 50.0% had no
      complications, 15.0% had ruptured membranes, 15.0% urinary tract infection, 7.5%
      hypertensive disorders, 7.5% transvaginal infection, 5.0% hematogenous infection,
      and 11.1% other complications. More than a half the neonates were males and 72.2%
      were born at term. Analysis of the degree of chorioamnionitis showed that 56.7%
      had grade I, 22.2% grade II, 4.4% grade III, 10.0% grade IV, and 6.7% grade V.
      Data were analyzed statistically by the Chi2 test for qualitative variables and
      by the Spearman test for correlation analysis. The higher grades of
      chorioamnionitis were observed in cases of maternal complications. We observed
      negative correlations between all parameters and the degree of fetal
      chorioamnionitis, which were significant regarding weight, length, thoracic
      circumference and Apgar score in the first and fifth minutes. CONCLUSIONS: The
      different patterns of chorioamnionitis were related to different maternal and
      fetal clinical features, affecting the life conditions of the newborn and the
      severity of morphological lesions found in stillbirths.

PMID- 22584811
TI  - [Cervical length as a predictor of the latent period and infection in preterm
      premature membranes rupture].
AB  - PURPOSE: To verify cervical length using transvaginal ultrasonography in pregnant
      women between 28 and 34 weeks of gestation, correlating it with the latent period
      and the risk of maternal and neonatal infections. METHODS: 39 pregnant women were
      evaluated and divided into groups based on their cervical length, using 15, 20
      and 25 mm as cut-off points. The latency periods evaluated were three and seven
      days. Included were pregnant women with live fetuses and gestational age between
      28 and 34 weeks, with a confirmed diagnosis on admission of premature rupture of
      membranes. Patients with chorioamnionitis, multiple gestation, fetal
      abnormalities, uterine malformations (bicornus septate and didelphic uterus),
      history of previous surgery on the cervix (conization and cerclage) and cervical
      dilation greater than 2 cm in nulliparous women and 3 cm in multiparae were
      excluded from the study. RESULTS: A <15 mm cervical length was found to be highly
      related to a latency period of up to 72 hours (p=0.008). A <20 mm cervical length
      was also associated with a less than 72 hour latency period (p=0.04). A <25 mm
      cervical length was not found to be statistically associated with a 72 hour
      latency period (p=0,12). There was also no significant correlation between
      cervical length and latency period and maternal and neonatal infection.
      CONCLUSION: The presence of a short cervix (<15 mm) was found to be related to a
      latency period of less than 72 hours, but not to maternal or neonatal infections.

PMID- 22584812
TI  - [Low dose of sublingual misoprostol (12.5 ug) for labor induction].
AB  - PURPOSE: To describe the maternal and perinatal outcomes after the use of 12.5 ug
      of sublingual misoprostol for labor induction in women with term pregnancy and a
      live fetus. METHODS: We conducted a multicenter, open and non-randomized clinical
      trial during the period from July to December 2009. We included 30 pregnant women
      with an indication for labor induction at term, carrying a live fetus, with a
      Bishop score of six or less, cephalic presentation, estimated fetal weight of
      less than 4,000 g and an amniotic fluid index greater than five. We excluded
      women with a previous uterine scar, non-reassuring fetal status, congenital
      anomalies, multiple pregnancy, intrauterine growth restriction, genital bleeding,
      and contraindications of vaginal delivery. A tablet of 12.5 ug sublingual
      misoprostol was administered every six hours, until the beginning of labor, with
      the maximum of eight doses. RESULTS: Labor was successfully induced in 90% of
      pregnant women. The mean interval between the first dose and the onset of uterine
      contractions and delivery was 14.3+/-11.7 hours and 25.4+/-13 hours,
      respectively. The frequency of vaginal delivery was 60%. Uterine tachysystole
      occurred in two pregnant women, being reversed in both cases without the need for
      cesarean section. Meconium-stained amniotic fluid was observed in four patients,
      and an Apgar score of less than 7 at five minutes in only one newborn.
      CONCLUSION: Maternal and perinatal outcomes were favorable after induction of
      labor with sublingual misoprostol at a dose of 12.5 ug every six hours. However,
      controlled trials are needed to compare this regimen with other doses and routes
      of administration.

PMID- 22584813
TI  - [Lacrimal dysfunction and pregnancy].
AB  - PURPOSE: To assess the prevalence of lacrimal dysfunction during pregnancy
      comparing it to non-pregnant women and to correlate these findings with obstetric
      history. METHODS: We interviewed 150 pregnant and 150 non-pregnant women for
      symptoms of dry eyes and obstetric history. Both groups underwent Schirmer I
      testing and responded to a questionnaire on dry eye symptoms. Patients with
      collagen diseases, medications associated with dryness of mucous membranes,
      hepatitis C infection and AIDS, previous intraocular inflammation and eye surgery
      were excluded. Data were analyzed by the Chi2 and Fisher tests when the data were
      nominal and by the Student's t-test and Mann-Whitney test when numerical. The
      level of significance was set at 5%. RESULTS: The two groups did not differ in
      symptoms of lacrimal dysfunction. The results of Schirmer's test were equal in
      both groups for the right eye (p=0.3) and left eye (p=0.3). However, pregnant
      women had a higher prevalence of at least one dry eye (p=0.004). The occurrence
      of dry eye in both groups (patients and controls) was associated with a greater
      number of full-term pregnancies/patient (p=0.04) but not with pregnancy time
      (p=0.5) or number of abortions (p=0.9). CONCLUSIONS: Pregnant women suffer more
      from lacrimal dysfunction than non pregnant women; in both groups the prevalence
      of tear dysfunction is more elevated in women with higher parity.

PMID- 22584814
TI  - [Nutritional status and quality of life of climacteric women].
AB  - PURPOSE: To associate the quality of life with the nutritional status of
      climacteric women. METHODS: This was a cross-sectional study on a sample of 200
      climacteric women aged 40 to 65 years who responded to a 24-hour food recall and
      to questions about socioeconomic factors and current, previous and family medical
      history. Body mass index (BMI), waist circumference (WC) and waist-hip ratio were
      used for anthropometric evaluation. To assess the quality of life, we applied the
      MRS-menopause rating scale. RESULTS: The average BMI and waist circumference were
      30.1 kg/m2 (obesity grade 1) and 99 cm (very increased risk for cardiovascular
      disease), respectively. Increased protein consumption and decreased fiber,
      calcium and vitamin D intake were detected. The most prevalent disease was
      hypertension, 48.5% of the women studied were taking medication for
      cardiovascular disease and 23% were taking antidepressant medications. Regarding
      quality of life, significant results related to BMI as well as blood pressure
      were found. CONCLUSIONS: A nutritional intervention aiming to correct or improve
      food consumption and anthropometric profile may result in health benefits for
      climacteric women. The prevalence of obesity, associated with a poorer quality of
      life, morbidity and mortality underscores the need for a feeding re-education
      program during the climacteric.

PMID- 22584815
TI  - [Correlation between age and antral follicles count in infertile women].
AB  - PURPOSE: To produce age-related nomograms for ovarian antral follicle count (AFC)
      in infertile women. METHODS: It was done a cross-sectional study of patients
      attended in the center of assisted reproduction Femina, from March 2010 to
      October 2011. The patients were submitted to transvaginal ultrasonography from
      day 2 to day 4 of their menstrual period. Patients included were between 21 to 45
      years old, with regular menses, two healthy ovaries, without any evidence of
      endocrinopathies and who gave written informed consent. Patients excluded were
      smokers, with galactosemia or ovarian cysts, with antecedents of liver disease,
      ovarian surgeries or who were treated with chemotherapy or radiotherapy. In order
      to check the evolution of the AFC in relation to patient age, we used the 5th,
      25th, 50th, 75th and 95th percentiles. Linear regression was carried out using
      these percentiles, permitting us to determine the effect of age on the CFA.
      RESULTS: A total of 172 patients with a mean age of 32.7 years were included in
      the trial. The male and tubal factors were the main causes of infertility,
      accounting for 65% of cases. The age-related nomogram for the 5th, 25th, 50th,
      75th and 95th percentiles of AFC revealed that changes were best fitted by a
      linear function. The percentiles that showed the highest correlations were 25 (r=
      0.9; p<0.001), 50 (r=-0.9; p<0.001) and 75 (r=-0.9; p<0.001). CONCLUSION: A
      nomogram was constructed correlating age with the different AFC percentiles in
      infertile women without endocrinopathies. This showed a linear pattern of decline
      in AFC with age in all percentiles. These nomograms could provide a reference
      guide for the clinician. However, future validation, with longitudinal data,
      still is needed.

PMID- 22584816
TI  - Use of dexmedetomidine for the treatment of alcohol withdrawal syndrome in
      critically ill patients: a retrospective case series.
AB  - Alcohol withdrawal syndrome (AWS) continues to be a challenge to manage in the
      ICU setting, and the ideal pharmacological treatment continues to evolve.
      Dexmedetomidine is a newer agent approved for short-term sedation in the ICU, but
      its use in the treatment of AWS has been limited. We report a retrospective case
      series of ten patients who were identified as receiving dexmedetomidine for AWS
      as designated by electronic pharmacy records. All subjects were male, with a mean
      age of 53.6 years, and a mean ICU length of stay of 9.3 days. They were all
      diagnosed with AWS by DSM-IV criteria. All the study patients received
      dexmedetomidine during their hospital course as a treatment for AWS. Studied
      variables included demographic data, dose and duration of dexmedetomidine, other
      pharmaceutical agents, and hemodynamics. Dexmedetomidine was safe to use in all
      patients, although mechanical ventilation was still required in three patients.
      With dexmedetomidine, the autonomic hyperactivity was blunted, with a mean 12.8%
      reduction in rate pressure product observed. Consideration should be given to the
      combined use of dexmedetomidine with benzodiazepines in the treatment of AWS.

PMID- 22584817
TI  - Impact of changes of positive end-expiratory pressure on functional residual
      capacity at low tidal volume ventilation during general anesthesia.
AB  - PURPOSE: Several reports in the literature have described the effects of positive
      end-expiratory pressure (PEEP) level upon functional residual capacity (FRC) in
      ventilated patients during general anesthesia. This study compares FRC in
      mechanically low tidal volume ventilation with different PEEP levels during upper
      abdominal surgery. METHODS: Before induction of anesthesia (awake) for nine
      patients with upper abdominal surgery, a tight-seal facemask was applied with 2
      cmH(2)O pressure support ventilation and 100 % O(2) during FRC measurements
      conducted on patients in a supine position. After tracheal intubation, lungs were
      ventilated with bilevel airway pressure with a volume guarantee (7 ml/kg
      predicted body weight) and with an inspired oxygen fraction (FIO(2)) of 0.4. PEEP
      levels of 0, 5, and 10 cmH(2)O were used. Each level of 5 and 10 cmH(2)O PEEP was
      maintained for 2 h. FRC was measured at each PEEP level. RESULTS: FRC awake was
      significantly higher than that at PEEP 0 cmH(2)O (P < 0.01). FRC at PEEP 0
      cmH(2)O was significantly lower than that at 10 cmH(2)O (P < 0.01). PaO(2)/FIO(2)
      awake was significantly higher than that for PEEP 0 cmH(2)O (P < 0.01).
      PaO(2)/FIO(2) at PEEP 0 cmH(2)O was significantly lower than that for PEEP 5
      cmH(2)O or PEEP 10 cmH(2)O (P < 0.01). Furthermore, PEEP 0 cmH(2)O, PEEP 5
      cmH(2)O after 2 h, and PEEP 10 cmH(2)O after 2 h were correlated with FRC (R =
      0.671, P < 0.01) and PaO(2)/FIO(2) (R = 0.642, P < 0.01). CONCLUSIONS: Results
      suggest that PEEP at 10 cmH(2)O is necessary to maintain lung function if low
      tidal volume ventilation is used during upper abdominal surgery.

PMID- 22584818
TI  - Survey of labor epidural analgesia and patient education for women in southwest
      China.

PMID- 22584819
TI  - Production of a thermostable alcohol dehydrogenase from Rhodococcus ruber in
      three different yeast species using the Xplor(r)2 transformation/expression
      platform.
AB  - The Xplor(r)2 transformation/expression platform was employed for comparative
      assessment of three different yeast species as hosts for synthesis of a
      thermostable nicotinamide adenine dinucleotide (NAD+)-dependent medium-chain
      alcohol dehydrogenase from Rhodococcus ruber strain 219. Using yeast ribosomal
      DNA (rDNA) integrative expression cassettes (YRCs) and yeast integrative
      expression cassettes (YICs) equipped with a selection-marker module and one, two
      or four expression modules for transformation of auxotrophic Arxula
      adeninivorans, Hansenula polymorpha, and Saccharomyces cerevisiae strains,
      quantitative comparison of the yield of recombinant alcohol dehydrogenase RR
      ADH6Hp in all three species was carried out. In all cases, the RR-ADH6H gene was
      expressed under the control of the strong constitutive A. adeninivorans-derived
      TEF1 promoter, which functions in all yeast species analyzed. Recombinant RR
      ADH6Hp accumulated intracellularly in all strains tested. The best yields of
      active enzyme were obtained from A. adeninivorans, with S. cerevisiae producing
      intermediate amounts. Although H. polymorpha was the least efficient producer
      overall, the product obtained was most similar to the enzyme synthesized by R.
      ruber 219 with respect to its thermostability.

PMID- 22584820
TI  - Contact-free cold atmospheric plasma treatment of Deinococcus radiodurans.
AB  - In this study we investigated the sensitivity of Deinococcus radiodurans to
      contact-free cold atmospheric plasma treatment as part of a project to establish
      new efficient procedures for disinfection of inanimate surfaces. The Gram
      positive D. radiodurans is one of the most resistant microorganisms worldwide.
      Stationary phases of D. radiodurans were exposed to cold atmospheric plasma for
      different time intervals or to ultraviolet C (UVC) radiation at dose rates of
      0.001-0.0656 J cm-2, respectively. A methicillin-resistant Staphylococcus aureus
      strain (MRSA) served as control for Gram-positive bacteria. The surface
      microdischarge plasma technology was used for generation of cold atmospheric
      plasma. A plasma discharge was ignited using ambient air. Surprisingly, D.
      radiodurans was sensitive to the cold atmospheric plasma treatment in the same
      range as the MRSA strain. Survival of both bacteria decreased with increasing
      plasma exposure times up to 6 log10 cycles (>99.999 %) within 20 s of plasma
      treatment. In contrast, UVC radiation of both bacteria demonstrated that D.
      radiodurans was more resistant to UVC treatment than MRSA. Cold atmospheric
      plasma seems to be a promising tool for industrial and clinical purposes where
      time-saving is a critical point to achieve efficient disinfection of inanimate
      surfaces and where protection from corrosive materials is needed.

PMID- 22584821
TI  - Amino acid substitutions in the N-terminus, cord and alpha-helix domains improved
      the thermostability of a family 11 xylanase XynR8.
AB  - The thermostability of xylanase XynR8 from uncultured Neocallimastigales rumen
      fungal was improved by combining random point mutagenesis with site-directed
      mutagenesis guided by rational design, and a thermostable variant, XynR8_VNE, was
      identified. This variant contained three amino acid substitutions, I38V, D137N
      and G151E, and showed an increased melting temperature of 8.8  degrees C in
      comparison with the wild type. At 65  degrees C the wild-type enzyme lost all of
      its activity after treatment for 30 min, but XynR8_VNE retained about 65 %
      activity. To elucidate the mechanism of thermal stabilization, three-dimensional
      structures were predicted for XynR8 and its variant. We found that the tight
      packing density and new salt bridge caused by the substitutions may be
      responsible for the improved thermostability. These three substitutions are
      located in the N-terminus, cord and alpha-helix domains, respectively. Hence, the
      stability of these three domains may be crucial for the thermostability of family
      11 xylanases.

PMID- 22584822
TI  - Structural and biomechanical characterizations of porcine myocardial
      extracellular matrix.
AB  - Extracellular matrix (ECM) of myocardium plays an important role to maintain a
      multilayered helical architecture of cardiomyocytes. In this study, we have
      characterized the structural and biomechanical properties of porcine myocardial
      ECM. Fresh myocardium were decellularized in a rotating bioreactor using 0.1 %
      sodium dodecyl sulfate solution. Masson's trichrome staining and SEM demonstrated
      the removal of cells and preservation of the interconnected 3D cardiomyocyte
      lacunae. Movat's pentachrome staining showed the preservation of cardiac elastin
      ultrastructure and vascular elastin distribution/alignment. DNA assay result
      confirmed a 98.59 % reduction in DNA content; the acellular myocardial scaffolds
      were found completely lack of staining for the porcine alpha-Gal antigen; and the
      accelerating enzymatic degradation assessment showed a constant degradation rate.
      Tensile and shear properties of the acellular myocardial scaffolds were also
      evaluated. Our observations showed that the acellular myocardial ECM possessed
      important traits of biodegradable scaffolds, indicating the potentials in cardiac
      regeneration and whole heart tissue engineering.

PMID- 22584823
TI  - Bifunctional polyethersulfone hollow fiber with a porous, single-layer skin for
      use as a bioartificial liver bioreactor.
AB  - A bioartificial liver bioreactor requires a bifunctional hollow fiber that is
      hemocompatible on one side and cytocompatible on the other side. In this study,
      we developed a single-layer skin polyethersulfone (PES) hollow fiber with smooth
      inner surface and rough/porous outer surface for an artificial liver bioreactor.
      The hemocompatibility of the inner surface was evaluated by hemolysis, complement
      activation and clotting time. The cytocompatibility of the outer surface with
      HepG2 cells was examined by morphology, proliferation and liver-specific
      functions. The inner surface of the PES hollow fiber exhibited lower hemolysis
      and complement activation than cellulose acetate (CA) hollow fiber and a
      prolonged blood coagulation time. HepG2 cells readily adhered to the outer
      surfaces of the PES hollow fibers, and proliferated to form multicellular
      aggregates with time. Furthermore, HepG2 cells cultured on the outer surface of
      the PES hollow fiber exhibited higher proliferation ability and liver-specific
      functions than those grown on the CA hollow fiber. These results suggest that the
      single-layer skin PES hollow fiber is a bifunctional hollow fiber with good
      hemocompatibility on the inner side and cytocompatibility on the outer side.
      Thus, porous and single-layer skin PES hollow fibers may have potential as
      materials for an artificial liver bioreactor.

PMID- 22584825
TI  - Unique syndio-selectivity in CO/styrene copolymerization reaction catalyzed by
      palladium complexes with 2-(2'-oxazolinyl)-1,10-phenanthrolines.
AB  - The reaction of the neutral Pd complex [Pd(CH(3))Cl(cod)] with the potentially
      terdentate 2-oxazolinyl phenanthroline ligands 1-3 affords the corresponding
      cationic dinuclear Pd-complexes 1a-3a, which can be isolated in the solid state
      in good yields. By treatment with AgPF(6) the complexes 1a-3a were converted into
      the corresponding hexafluorophosphate derivatives 1b-3b, where both the ligand
      units feature a terdentate coordination around the two Pd-centres with the
      phenanthroline fragment of each unit displaying a chelate coordination to one Pd
      centre, while the corresponding oxazolinyl pendant acts as a bridging ligand
      towards the second Pd-centre. The persistence of this dimeric structure of 1b-3b
      in CD(2)Cl(2) solution was confirmed by (15)N-NMR experiments at natural
      abundance, which clearly show the binding to the metal of all of the nitrogen
      donors, as well as the overall C(2) symmetry of the compound. In consequence of
      the different strengths of the relevant ion-pair, the dimeric structure of the
      complex undergoes partial fragmentation in the case of the chloride derivatives
      1a-3a, as evidenced from the (15)N-NMR spectra. Complexes 1b-3b are active
      catalysts in styrene alternate carbonylation, where, under very mild conditions
      (30  degrees C and 1 atm of CO), they provide oligomers with 3-5 repetitive units
      as the exclusive or prevailing product. When traces of the CO/styrene polyketones
      are also formed, their (13)C-NMR characterization shows that they are
      stereochemically homogeneous with a unique syndio-tacticity. This result implies
      that Pd-complexes able to induce a complete enantioface discrimination in the
      insertion step of the alkene during the catalytic cycle of the styrene alternate
      carbonylation have been produced for the first time.

PMID- 22584824
TI  - Efficacy of silver treated catheters for haemodialysis in preventing bacterial
      adhesion.
AB  - The growing resistance of many strains of bacteria to antibiotics and antiseptics
      is becoming a serious problem in medicine. Nano-silver is one of the most
      prominent products in medicine because it exhibits unusual physicochemical
      properties and a strong biological activity. In this work an innovative silver
      deposition technology was applied to temporary polyurethane catheters for
      haemodialysis. The working conditions of catheters were reproduced through
      laboratory equipment that ensured the flow of deionized water and simulated body
      fluid inside the lumina at corporeal temperature. The growth and the adhesion of
      Staphylococcus aureus on the surface of the device were studied through
      fluorescence microscopy. ICP-AES was adopted to calculate the amount of silver
      released from the substrate. The stability of the coating during the whole
      working life of the device was demonstrated through thermo-gravimetric analysis.

PMID- 22584826
TI  - Pressure amorphized ices--an atomistic perspective.
AB  - We offer our viewpoint on the nature of amorphous ices produced by pressurization
      of crystalline ice Ih and the inter-relationship between them from an atomistic
      perspective. We argue that the transformation of high density amorphous (HDA) ice
      from crystalline ice is due to a mechanical process arising from the instability
      of the ice Ih structure. The densification of HDA upon thermal annealing under
      pressure is a relaxation process. The conversion of the densified amorphous ice
      to a lower density form (LDA) upon the release of pressure can be attributed to a
      similar process. It is speculated that amorphous ices are metastable frustrated
      structures due to the large activation barriers associated with proton
      reorientation in the formation of the underlying stable crystalline ice
      polymorphs.

PMID- 22584827
TI  - Insights into proximal pouch dilatation following adjustable gastric banding--a
      form of inattentional blindness?

PMID- 22584828
TI  - Retraction statement. Paper by Michael W. Miller and Huaiyu Hu [Developmental
      Neuroscience 2009;31:50-57].

PMID- 22584829
TI  - Inhibition of leukemia proliferation by a novel polysaccharide identified from
      Monascus-fermented dioscorea via inducing differentiation.
AB  - Monascus-fermented products offer valuable therapeutic benefits and have been
      extensively used in East Asia. However, the polysaccharide obtained from Monascus
      fermented products has never been investigated. This study evaluated the effects
      of dioscorea polysaccharide (DPS) and red mold dioscorea polysaccharide (RMDPS)
      on differentiation of leukemic THP-1 cells. DPS and RMDPS inhibited THP-1 cells
      proliferation in dose- and time-dependent manners. The differentiation induction
      (macrophage-like cells) was observed when THP-1 cells were treated with DPS and
      RMDPS for 5 days. Superoxide anion production, phagocytic capacity, and cytokine
      secretion confirmed activity for differentiating THP-1 cells. Results indicated
      that RMDPS elevated reactive oxygen species production and immune activity,
      including phagocytosis, interleukin-1beta (IL-1beta), tumor necrosis factor-alpha
      (TNF-alpha), and interferon-gamma (IFN-gamma) productions in THP-1 cells, which
      was greater than that seen with DPS. These results may be attributed to Monascus
      fermentation altering the carbohydrate components and polysaccharide structure.
      RMDPS may serve as a novel material and functional ingredient to exert anticancer
      capacity.

PMID- 22584830
TI  - Conditions found among pediatric survivors during the early response to natural
      disaster:  a prospective case study.
AB  - BACKGROUND: Major natural disasters may provoke a mass casualty situation, and
      children tend to represent an important proportion of the victims. The purpose of
      this study was to prospectively record medical conditions presented by pediatric
      survivors of a major natural disaster to determine the type of medical
      specialists most needed during the acute phase of relief response. METHODS: After
      the 2010 Haiti earthquake, age, sex, date of presentation, diagnosis, and
      treatment provided were prospectively recorded for all patients less than 18
      years old treated by a medical relief team. Patients were then allocated to 1 of
      the 2 groups: surgical (traumatism or surgical disorder) and medical (medical
      disorder). Medical activity lasted for 43 days. RESULTS: Four hundred seventy-one
      of the 796 treated patients were less than 18 years old. Two hundred forty-four
      (52%) were assigned to the surgical group and 227 (48%) to the medical group. As
      there was a substantial decrease in the number of new surgical patients
      registered on day 11 of activity, we arbitrarily defined an early period (until
      day 10 of activity) and a late period (beginning on day 11 of activity). Data
      obtained from the 147 new patients registered during the early period revealed
      134 (91%) surgical patients and 13 (9%) medical patients. Eighty-eight percent of
      patients needed specialized care for traumatic orthopaedic lesions, and
      procedures under anesthesia or sedation were mainly (98%) performed for traumatic
      conditions. Data obtained for the 324 new patients registered during the late
      period revealed 110 (34%) surgical patients and 214 (66%) medical patients. There
      was a switch from high surgical needs to more routine medical and surgical care,
      with less procedures (88%) for the treatment of traumatic lesions. CONCLUSIONS:
      Pediatric orthopaedic surgeons have a major role to play in the acute phase of
      relief response to potentially minimize long-term physical and psychosocial
      disability associated with these complex injuries in growing patients. LEVEL OF
      EVIDENCE: Economic or decision analyses, level II.

PMID- 22584831
TI  - Operative treatment of adolescent clavicle fractures with an intramedullary
      clavicle pin.
AB  - BACKGROUND: Adolescent clavicle fractures have traditionally been treated
      nonoperatively; however, recent literature in adults has shown improved outcomes
      with operative treatment of displaced and shortened clavicle fractures. It has
      been suggested that these results may translate to adolescents. This study
      presents an initial look at outcomes for operative treatment of displaced
      midshaft clavicle fractures in adolescents using an intramedullary clavicle pin.
      METHODS: Seventeen adolescent patients treated for a displaced, shortened
      midshaft clavicle fracture with an intramedullary clavicle pin between November
      2007 and August 2009 were evaluated. Preoperative displacement, fracture union,
      and complications were reviewed, and shoulder scores were determined using the
      patient self-report section of the American Shoulder and Elbow Surgeons
      Standardized Shoulder Assessment Form. RESULTS: Fracture union occurred in all 17
      patients by 12 weeks. Average patient age was 15.8 years and ranged from 13 to 18
      years. All but 2 implants were electively removed. The most common postoperative
      complaint was prominent hardware, which resolved after elective removal. There
      were no infections and only 1 patient reported decreased sensation at the
      incision site. Ten patients returned the American Shoulder and Elbow Surgeons
      form at an average time of 16.6 months after surgery. The average pain score was
      44.2 of a possible 50 points. The average functional score was 44.3 of a possible
      50 points. No patients reported severe difficulty with work activities and only 1
      patient reported severe difficulty with sporting activities. CONCLUSIONS:
      Operative treatment with an intramedullary clavicle pin seems to be a safe and
      effective treatment method for displaced midshaft clavicle fractures in
      adolescents. LEVEL OF EVIDENCE: Therapeutic level IV.

PMID- 22584832
TI  - Changing practice patterns:  the impact of a randomized clinical trial on
      surgeons preference for treatment of type 3 supracondylar humerus fractures.
AB  - BACKGROUND: A recent prospective randomized clinical trial (RCT) for comparison
      of medial and lateral entry pins with lateral entry pins for treatment of
      Gartland type 3 supracondylar humerus fractures (SCHF) was published, validating
      the national trend toward treatment of this injury with only lateral entry pins.
      But have surgeons actually changed their practice as a result of these recent
      data? The purpose of this study was to compare pin configuration, loss of
      reduction and rate of nerve injuries before and after the RCT. METHODS: This was
      a retrospective review of patients with Gartland type 3 SCHF who were treated
      before the RCT (April 2000 to April 2003: 141 patients) and after the trial
      (April 2006 to April 2009: 126 patients). Eight surgeons were included. Patient
      demographic data, pin configuration, neurovascular status, and radiographic
      results were compared. Comparisons between the pretrial cohort and the posttrial
      cohort as a group as well as for each individual surgeon were performed.
      Comparisons included the choice of pin configuration, incidence of loss of
      radiographic reduction, iatrogenic nerve injuries, return to the operating room,
      and infection before and after the clinical trial. RESULTS: There was a
      statistically different pin configuration in the pretrial group compared with the
      posttrial group (P<0.0001) with the posttrial group having a much higher
      percentage of bicolumnar lateral entry only pins. Five out of 8 surgeons
      individually had a statistically significant change in their practice pattern for
      pin configuration. There was no difference from pretrial to posttrial in loss of
      radiographic reduction, infection rate, iatrogenic nerve injuries, or return to
      the operating room. CONCLUSIONS: Data showing change in surgeon practice have
      been relatively sparse. In this group of surgeons who participated in an RCT,
      there was a statistically significant change in pin configuration for treatment
      of Gartland type 3 SCHF after the results of the RCT were known. The change in
      clinical practice did not have an effect on outcomes. LEVEL OF EVIDENCE: Level
      III.

PMID- 22584833
TI  - Treatment of displaced pediatric supracondylar humerus fracture patterns
      requiring medial fixation: a reliable and safer cross-pinning technique.
AB  - INTRODUCTION: Treatment of displaced Gartland type 3 supracondylar humerus
      fractures in children may include closed reduction and percutaneous pinning. The
      pin configuration may be all-lateral entry or cross-pin. Despite the improved
      stability possible with cross-pinning, there is an inherent iatrogenic risk to
      the ulnar nerve of about 6%. As medial fixation may be necessary for certain
      fracture patterns, this study was conducted to evaluate the risk of ulnar
      neuropathy using a technique here described and developed to minimize injury to
      this structure. METHODS: A retrospective review was performed on all children
      treated for a supracondylar humerus fracture at our institution between 2003 and
      2010. All the type 3 displaced fractures were placed into 2 groups: lateral-entry
      pinning and cross-pinning. The 2 groups were then compared for risk of ulnar
      nerve injury, and a post hoc power analysis was performed. RESULTS: A total of
      381 supracondylar humerus fractures met the inclusion criteria. Our cross-pinning
      technique was used in 187 (49%) of the children with a mean age of 5.8 years
      (range, 0.92 to 13.92 y). There were 4 ulnar nerve injuries in the entire cohort
      and 2 sustained as iatrogenic injuries in the cross-pinning group (1.1%). There
      was no significant difference between our 2 groups in regard to risk of ulnar
      nerve injury (P=0.24). There is a statistically significant lower risk of ulnar
      nerve injury in our cross-pinning technique than previously described techniques
      (P=0.0028), with a post hoc power analysis of 93%. CONCLUSIONS: Despite the
      inherent risk for iatrogenic nerve injury with cross-pinning completely displaced
      supracondylar humerus fractures, there is often a need to use this technique to
      improve fixation and stability of the fracture. Our method of cross-pinning is
      safe and reproducible for providing fracture stability with a significant
      decrease in the risk of iatrogenic ulnar nerve injury (1 in 94) when a medial pin
      is required. LEVEL OF EVIDENCE: Level III-therapeutic studies.

PMID- 22584834
TI  - Pediatric Monteggia fractures: a single-center study of the management of 40
      patients.
AB  - INTRODUCTION: Early identification and conservative management of pediatric
      Monteggia fractures has been shown to correlate with good results. Nevertheless,
      several authors advocate more aggressive management with open reduction and
      internal fixation (ORIF) for unstable fractures. We herein present the experience
      of a tertiary pediatric hospital in the management of Monteggia fractures.
      METHODS: Forty patients with Monteggia fractures (26 male and 14 female) were
      admitted and treated over a period of 20 years (1989 to 2009). The age of the
      patients ranged between 3 and 14 years (mean 7.5 y). On the basis of the Bado
      classification, 28 fractures were type I, 3 were type II, 8 type III, and 1
      fracture was classified as type IV. Out of the 40 patients, 32 were managed with
      manipulation under anesthesia (MUA) and above-elbow plaster, whereas 8 underwent
      ORIF of the ulna. RESULTS: To assess outcomes, the Bruce, Harvey, and Wilson
      scoring system was used. Range of movement, pain, and deformity were evaluated to
      class an outcome as excellent, good, fair, or poor. Patients were followed up for
      an average of 4.6 years (range, 1 to 7 y). All patients in the MUA group had
      excellent results. In the ORIF group, 8 out of 9 patients had good results.
      DISCUSSION AND CONCLUSIONS: According to our recorded experience, conservative
      management of Monteggia fractures, when indicated, results in excellent outcomes.
      In cases where emergency MUA fails to achieve or maintain reduction, the choice
      of ORIF has also demonstrated good results. Early diagnosis and management are of
      paramount importance as mismanaged cases demonstrate less satisfactory results.
      LEVEL OF EVIDENCE: Level IV. Case series.

PMID- 22584835
TI  - The role of clinically significant venous thromboembolism and thromboprophylaxis
      in pediatric patients with pelvic or femoral fractures.
AB  - BACKGROUND: In adults, pelvic and femoral fractures have a known association with
      venous thromboembolic disease and, thus, thromboprophylaxis is the standard of
      care. However, similar data for children are scarce, and recommendations for
      pediatric prophylaxis are less clear. Our goals were to: (1) analyze the
      predisposing risk factors, prevalence, and outcome (including mortality) of
      clinically significant venous thromboembolism; (2) investigate the use of
      thromboprophylaxis in pediatric trauma patients and ages at which it was given;
      and (3) determine the impact that central venous catheters had on the occurrence
      of venous thromboembolism. METHODS: We reviewed the records of all pediatric
      patients with pelvic or femoral fracture admitted to our hospital from 1990
      through 2009 for occurrence of venous thromboembolism and related mortality, use
      and effect of central venous catheters, use of thromboprophylaxis (heparin,
      warfarin, enoxaparin, or factor-X inhibitors), and patient age at administration.
      Of the 1782 patients, 948 had electronically searchable medication (and device)
      records. Ninety-five percent confidence intervals were found for all proportions
      with sample sizes >100, and an unpaired t test was used to compare the average
      age at which thromboprophylaxis was given with the average age of the total
      population. RESULTS: Of the 1782 patients, there were 3 (0.17%) diagnoses of deep
      vein thrombosis and no diagnoses of pulmonary embolism; there was no related
      mortality. Of the medication subset (948 patients) only 83 (8.8%) received some
      type of thromboprophylaxis. The average age of patients given thromboprophylaxis
      was 14.65 years (SD, 2.34). No central venous catheter was associated with any of
      the patients who had a venous thromboembolic event. CONCLUSIONS:
      Thromboprophylaxis was used only occasionally at our institution; >91% of
      patients did not receive such treatment. No morbidity or mortality was reported
      related to venous thromboembolism in pediatric patients with femur or pelvic
      fracture for whom thromboprophylaxis was used. LEVEL OF EVIDENCE: Level II,
      retrospective study.

PMID- 22584836
TI  - Long-term retrospective of the Kaneda anterior scoliosis system in thoracic
      adolescent idiopathic scoliosis.
AB  - BACKGROUND: Currently, the Kaneda anterior scoliosis system (KASS) is reported to
      be acceptable for the treatment of adolescent idiopathic scoliosis (AIS),
      particularly thoracolumbar and lumbar deformities. Its use in thoracic AIS is not
      as established. METHODS: Retrospective analysis of long-term results in patients
      treated with the KASS for thoracic AIS to determine specific factors associated
      with success or failure. We analyzed 16 consecutive patients who met the
      following criteria: thoracic AIS, anterior spinal fusion and KASS, and >=24
      months of follow-up or progression to failure, defined as the need for revision
      surgery or progression of the main thoracic curve (MTC) >=50 degrees. Comparison
      of the MTC on the preoperative, postoperative, and final follow-up was the major
      evaluation criteria. On the basis of data analysis, patients were divided for
      comparison into 2 study groups: nonfailure group (n=11) and failure group (n=5).
      Statistical analysis was performed using paired and independent t tests. RESULTS:
      All curves were classified as Lenke 1 (n=14) and 2 (n=2). Mean age at surgery and
      levels fused were 14.6+/-2.7 years and 5+/-1 vertebrae, respectively. Mean follow
      up was 4.2 years (range, 1.0 to 6.2 y). The failure group consisted of 5 patients
      that progressed to >=50 degrees. In the nonfailure group, the mean MTC
      preoperative, postoperative, and at final follow-up were 52+/-8, 19+/-8, and 29+/
      7 degrees, respectively. In the failure group, these measurements were 74+/-11,
      35+/-8, and 56+/-12 degrees, respectively. CONCLUSIONS: This retrospective, long
      term follow-up study found more KASS failures in thoracic AIS than previously
      reported. Even in the nonfailure group, 5 of the 11 patients progressed 10
      degrees or more. Our results indicate an increased incidence of KASS failure with
      preoperative MTC curve >=70 degrees. We consider an MTC>=70 degrees a likely
      contraindication for KASS instrumentation for thoracic AIS. Four of the 5
      failures were fused short of the end vertebrae either proximally, distally, or
      both. Although short apical fusions were popular during the time these cases were
      done, fusion to the end vertebrae is an important principle for anterior fusions.
      Reaching the upper end vertebrae may be more difficult in these larger curves. We
      also recommend continued follow-up past 2 years as progression can occur after
      this time. LEVEL OF EVIDENCE: Retrospective comparative study, level III.

PMID- 22584837
TI  - Effectiveness of the Charleston night-time bending brace in the treatment of
      adolescent idiopathic scoliosis.
AB  - BACKGROUND: Part-time or night-time bracing has been introduced to address the
      poor compliance and psychological burden of full-time bracing. The results of
      various bracing methods vary, however, due to a lack of consistent inclusion
      criteria and definitions of brace effectiveness. We have evaluated the
      effectiveness of the Charleston night-time bending brace in the treatment of
      adolescent idiopathic scoliosis based on the new standardized criteria proposed
      by the Scoliosis Research Society. METHODS: To be included in this study,
      patients met the following criteria proposed by the Scoliosis Research Society:
      diagnosis of adolescent idiopathic scoliosis, age 10 years and older when the
      orthosis was prescribed, Risser 0-2, a primary curve magnitude of 25 to 40
      degrees, and no prior treatment. A total of 95 patients (87 girls, 8 boys) were
      included. RESULTS: At skeletal maturity, 80 patients (84.2%) had 5 degrees or
      less curve progression and 15 (15.8%) had 6 degrees or more progression. Seven
      patients (7.8%) were recommended to undergo or underwent surgery before skeletal
      maturity. Eleven patients (12.6%) progressed beyond 45 degrees. According to
      these 3 criteria, the Charleston night-time brace was successful in 74 patients
      (77.9%). Depending on curve type, we observed success rates of 78.3% (47/60) for
      double, 71.4% (15/21) for thoracic, 83.3% (5/6) for thoracolumbar, and 87.5%
      (7/8) for lumbar curves. Success rates of 80.0% (36/45) and 76.0% (38/50) were
      observed in patients with curve magnitudes at bracing of 25 to 30 degrees and 31
      to 40 degrees, respectively. Patients with high apex curves had a 67.6% (23/34)
      success rate, and those with low apex curves had 83.0% (39/47) success rate.
      Brace success rates among patients with initial Risser signs of 0, 1, and 2 were
      68.8% (22/32), 80.6% (25/31), and 84.4% (27/32), respectively. CONCLUSIONS:
      Compared with the results of previous natural history and conventional brace
      study, the Charleston night-time bending brace is effective for the treatment of
      adolescent idiopathic scoliosis. LEVEL OF EVIDENCE: Level VI.

PMID- 22584838
TI  - Does using the medial or lateral humeral line improve reliability of Baumann
      angle measurement on plain x-ray? The effect of humeral length visualized on the
      x-ray.
AB  - BACKGROUND: Baumann angle (BA) is a common measure of coronal plane alignment of
      the distal humerus. We hypothesize that the reliability of measuring BA would be
      improved by using the medial and lateral cortical margins of the humerus seen on
      plain x-ray, rather than the estimated central humeral line, which is the
      "standard" technique. Further, we analyze whether the amount of humerus visible
      on the film improves the reliability of the method. METHODS: A total of 71
      anteroposterior elbow digital radiographs from patients aged 0 to 12 were
      measured 3 times by 5 qualified observers. Each digital measurement included (1)
      BA using the estimated central humeral line; (2) BA using the medial humeral line
      (BA-MHL); and (3) BA using the lateral humeral line (BA-LHL). Inadequate
      radiographs or those showing any indication of current or previous fracture were
      excluded. Intraobserver reliability was estimated for each rater using a 1-way
      analysis of variance model and interobserver reliability of each set of
      measurements was estimated using a 2-way analysis of variance. RESULTS: The mean
      and SD for the BA, BA-MHL, and BA-LHL in females were 70.0 (6.73), 68.0 (6.84),
      and 72.3 (7.93), respectively, and for males 73.0 (5.22), 70.0 (5.56), and 76.0
      (6.18), respectively. Intraobserver reliability (intraclass correlation
      coefficient) for BA, BA-MHL, and BA-LHL averaged 0.85, 0.92, and 0.90,
      respectively. Average interobserver reliability (intraclass correlation
      coefficient) for BA, BA-MHL, and BA-LHL were 0.79, 0.71, and 0.76, respectively.
      Intraobserver and interobserver reliability of BA and BA-LHL were significantly
      improved when at least 7 cm of humerus was visible on the x-ray, as compared with
      <7 cm visible. CONCLUSIONS: Intrarater reliability is better for both BA-LHL and
      BA-MHL than for standard BA (using the estimated central humeral axis).
      Interrater reliability was best using standard BA. Reliability of all methods is
      improved when >7 cm of the distal humerus is visible on the radiograph. In
      addition, at least 7 cm of the distal humerus on anteroposterior radiographs
      improves reliability of measuring BA. LEVEL OF EVIDENCE: Diagnostic study-Level
      II.

PMID- 22584839
TI  - The intrarater and interrater reliability of glenoid version and glenohumeral
      subluxation measurements in neonatal brachial plexus palsy.
AB  - BACKGROUND: Progressive and disabling glenohumeral dysplasia commonly occurs as a
      secondary deformity in children with neonatal brachial plexus palsy (NBPP). A
      number of methods for quantifying glenohumeral dysplasia are currently in use;
      however, the most commonly reported quantitative measures have yet to be
      validated. The present study assesses the intrarater and interrater reliability
      of the glenoid version angle (GVA) and percent of the humeral head anterior to
      the scapular line (PHHA) measurements on axial magnetic resonance images.
      METHODS: Axial magnetic resonance images of the shoulder girdle of 25 children
      with NBPP were selected to represent a wide range of glenohumeral dysplasia
      severity. An axial image was preselected for each measurement. Six examiners (3
      orthopaedic surgeons, 2 musculoskeletal radiologists, and an epidemiologist)
      digitally measured the GVA and PHHA on each image twice, with each measurement
      separated by 2 to 14 days and the order of image presentation placed in a
      different arrangement for each measurement set. Intrarater and interrater
      reliability was assessed with the intraclass correlation coefficient (ICC).
      Measurement errors for the GVA and PHHA measurements and the variances associated
      with the scapular and glenoid lines were calculated. RESULTS: Using the Fleiss
      criteria, intrarater reliability was excellent, with ICCs averaging 0.909 (95%
      CI: 0.840, 0.940) for GVA and 0.891 (95% CI: 0.815, 0.921) for PHHA. Interrater
      reliability was excellent, with ICCs of 0.848 (95% CI: 0.788, 0.909) for GVA and
      0.874 (95% CI: 0.815, 0.934) for PHHA. The GVA and PHHA measurement errors were
      +/-6.4 degrees and +/-7.2%, respectively. In a subset of 141 images measured, the
      between-image variance in the scapular line was greater than the glenoid line by
      a 1.61:1 ratio. CONCLUSIONS: : The present study demonstrates excellent
      intrarater and interrater reliability of standard measurements of glenohumeral
      dysplasia in NBPP. The measurement errors for both measurements were comparable
      with other standard measures (e.g., Cobb angle). The scapular line exhibited a
      greater variance than the glenoid line, which identifies an opportunity for
      improvement in the GVA measurement. LEVEL OF EVIDENCE: Diagnostic study; level
      III.

PMID- 22584840
TI  - Corrective dome osteotomy using the paratricipital (triceps-sparing) approach for
      cubitus varus deformity in children.
AB  - BACKGROUND: Dome osteotomy has been described extensively in literature to
      correct posttraumatic cubitus varus deformity in children. Most case series on
      dome osteotomy using the posterior triceps-splitting approach report a decreased
      postoperative range of motion (ROM). We prospectively analyzed the results of
      dome osteotomy using the soft-tissue preserving paratricipital, (triceps-sparing)
      approach with respect to correction of deformity and preservation of elbow ROM.
      METHODS: During 2006 to 2009, 24 children with cubitus varus deformity after
      supracondylar humerus fracture were treated with a dome osteotomy using the
      triceps-sparing approach. The follow-up period varied between 22 and 36 months
      (average, 27.6 mo). The average interval between injury to surgery was 26.7
      months. The average age of the patients was 9.2 years. RESULTS: The average
      preoperative carrying angle (humerus-elbow-wrist angle, HEW) was -17.1 degrees
      (range, -8 to -30 degrees), whereas the average postoperative carrying (humerus
      elbow-wrist) angle was +11.7 degrees (range, -12 to +16 degrees) with a mean
      correction of 28.8 degrees. The average preoperative ROM in the flexion/extension
      arc was 126.8 degrees and the average postoperative ROM was 132.1 degrees (range,
      110 to 140 degrees). The lateral condylar prominence index changed from an
      average of -9.5% preoperatively to an average of -15.2% postoperatively.
      Excellent results were seen in 14 patients, whereas 9 had a good outcome.
      CONCLUSIONS: Supracondylar humeral dome osteotomy using the paratricipital
      approach for cubitus varus deformity allows correction of deformity, prevents
      lateral condylar prominence and avoids loss of elbow motion. LEVEL OF EVIDENCE:
      IV.

PMID- 22584841
TI  - Intra-articular venous malformations of the knee.
AB  - BACKGROUND: Intra-articular venous malformations (IAVM) of the knee represent a
      rare group of low-flow vascular malformations, mainly reported in the literature
      as synovial hemangiomas, usually with an onset in early childhood. The main
      symptoms and signs are knee pain, swelling, and hemarthrosis. These lesions are
      slowly progressive and can lead to chronic synovitis and joint damage. Confusing
      nomenclature and classification of these lesions have often led to misdiagnosis
      and inappropriate treatment. We report our experience in the treatment of 14
      consecutive patients affected by knee IAVM. METHODS: We carried out a
      retrospective study based on the review of the medical records and diagnostic
      imaging of the patients admitted to our department from October 1999 to June
      2009, and discharged with the final diagnosis of IAVM of the knee. RESULTS: We
      observed 14 consecutive patients (8 boys, 6 girls); the median age at symptom
      onset was 5 years (range, 2.5 to 13 y). Magnetic resonance imaging was diagnostic
      in all cases. Surgical resection associated with a wide synoviectomy was the
      therapeutic procedure of choice in all cases. Within 6 months after surgery and
      physiotherapy, all the patients were symptom free with a full or at least
      acceptable knee range of motion. CD34 staining carried out in the last 7 cases of
      our series showed labeling of the endothelium of the thick-walled vessels,
      whereas the endothelium of the thin-walled vascular spaces was not stained. This
      finding of unstained vascular spaces suggests that a component of lymphatic
      vessels mixed with dysplastic blood vessels may be frequently present in these
      abnormalities. CONCLUSIONS: Magnetic resonance imaging plays a pivotal role in
      identifying the lesion. Surgical excision is always indicated and should be
      performed as early as possible to avoid lesion progression and to reduce the risk
      of chondral degeneration. According to the microscopic features of our resected
      specimens, we suggest that these lesions of the knee should be more properly
      named as IAVM instead of hemangiomas. LEVEL OF EVIDENCE: Level IV.

PMID- 22584842
TI  - Hip range of motion in children:  what is the norm?
AB  - BACKGROUND: Abnormal range of motion (ROM) is a common sign of pathology in the
      pediatric hip, yet there are little data in the literature defining what the
      normal hip ROM is in children. The purpose of this study was to establish
      normative values for hip ROM in children of varying ages. METHODS: We performed
      an Institutional Review Board approved, prospective study of otherwise healthy
      patients receiving fracture care at our institution. Inclusion criteria were boys
      and girls aged 2 to 17, who were being treated for an isolated upper extremity
      injury and who had no underlying musculoskeletal condition, history of lower
      extremity injury, or other systemic diagnosis. All patients were evaluated with a
      standard measurement technique using the same double-long-armed goniometer.
      Supine abduction, adduction, and hip flexion were measured with care taken to
      stabilize the pelvis. Internal and external rotation in flexion were assessed
      with both the hip and knee flexed to 90 degrees. In the prone position, hip
      extension was recorded as was internal and external rotation in extension. Left
      and right measurements were averaged to produce a single data point for each
      index. On the basis of a power analysis (to detect a minimal detectable
      difference of 6 degrees), 2 separate cohorts of 23 patients were randomly
      selected for the assessment of intraobserver and interobserver reliability.
      RESULTS: We measured 504 hips in 252 pediatric patients, including 163 boys and
      89 girls. We found a decreasing trend in ROM for almost all indices with
      advancing age, although this decline was less apparent among girls. Intraobserver
      reliability demonstrated excellent agreement (intra class correlation
      coefficient>0.81) for all indices. Interobserver assessments revealed excellent
      agreement for abduction, external rotation in flexion, internal rotation in
      extension, and external rotation in extension. Substantial agreement (intra class
      correlation coefficient, 0.61 to 0.8) was found for adduction, flexion,
      extension, and internal rotation in flexion. CONCLUSIONS: Normative values for
      hip ROM in children of varying ages have been established with acceptable
      intraobserver and interobserver reliability. LEVEL OF EVIDENCE: Level II
      (Diagnostic).

PMID- 22584843
TI  - Treatment results of late-relapsing idiopathic clubfoot previously treated with
      the Ponseti method.
AB  - BACKGROUND: Idiopathic clubfoot has a stubborn tendency for relapse, with most
      relapses happening within the first few years. However, a few patients relapse
      later, adding to the complexity of management. This study investigates the
      treatment results of relapsing clubfoot deformity after age 4. METHODS: Thirty
      nine patients (60 feet) met the inclusion criteria. Age at initial treatment,
      previous treatment, number of casts and tenotomies, length of bracewear, and
      relapse presentation were recorded. Treatment of late relapse followed 1 of the 5
      courses: (1) observation only (4 feet); (2) bracing (26 feet); (3) casting
      followed by bracing (7 feet); (4) casting followed by tibialis anterior tendon
      transfer (TATT) with or without open tendo Achilles lengthening (TAL) (8 feet);
      or (5) primary TATT+/-TAL (15 feet). Of the 37 feet treated initially with
      observation, bracing, or casting, 33 went on to have TATT (89%). Multiple other
      concurrent procedures were performed according to the specific deformities. These
      included plantar fasciotomy (6 feet), extensor hallicus longus recession (5
      feet), limited posterior release 5 feet, and others (3 feet). Five feet underwent
      revision surgery after TATT, 2 of which ended in triple arthrodeses. RESULTS:
      Average age at final follow-up was 23.3 years (range, 8.5 to 50.6 y). Ninety
      percent of patients wore regular shoes, 41% had pain with activities, but only
      18% were limited in function by their feet. Average ankle dorsiflexion was 6
      degrees (range, -15 to 25 degrees). Mild residual deformities were noted in 55%
      of feet. CONCLUSIONS: This challenging group of patients with apparently
      persistent deforming biology achieves acceptable results with individualized
      evaluation and treatment of their foot deformities. LEVEL OF EVIDENCE:
      Therapeutic level IV.

PMID- 22584844
TI  - Achilles tenotomy as an office procedure: safety and efficacy as part of the
      Ponseti serial casting protocol for clubfoot.
AB  - BACKGROUND: Ponseti demonstrated the correction of clubfoot in infants using
      manipulation followed by the application of well-molded long-leg plaster casts.
      Percutaneous Achilles tenotomy was recommended to correct residual equinus
      contracture in approximately 80% of cases. In the current study, we evaluated the
      safety of this practice for the treatment of clubfoot when performed as an
      "office procedure" without sedation or general anesthesia during the final stage
      of the serial casting protocol. PATIENTS AND METHODS: We retrospectively
      collected data regarding babies who underwent serial manipulation and casting
      according to the Ponseti protocol for the treatment of clubfoot. All babies
      managed in the outpatient clinic between 2006 and 2010 were included. Tenotomy
      was indicated when the forefoot was completely corrected and if the hind-foot
      showed rigid equinus. Tenotomy was performed by a single scalpel stab in the
      outpatient clinic, using topical and local anesthesia (without general anesthesia
      or sedation). The cast was then applied and kept on for 3 weeks. Babies were
      discharged home after 1 hour of supervision. Surgical reports regarding Achilles
      tenotomy were reviewed, and data were collected from postoperative notes. We
      specifically looked for perioperative complications, recovery unit notes, and
      hospital readmission. RESULTS: Fifty-six babies (83 feet) were included in the
      current study. There were 40 males and 16 females, and 27 of them had bilateral
      clubfoot. Three babies (0.5%) had complex (syndrome-related) clubfoot; familial
      risk was known in 6 (11%) babies. Forty-one (73%) babies were indicated for
      Achilles tenotomy. Tenotomy was performed after an average of 5 casts (range, 3
      to 9). No adverse events were related to local anesthesia and/or the procedure
      itself, and there was no delay in discharge in any of the operated babies. One
      baby was evaluated in the emergency room 3 days after the procedure because of
      (unfounded) parental concern of swelling inside the cast. All other babies had an
      uneventful course. Retenotomy was performed in 7 babies (12 feet); 2 of them (4
      feet) had complex clubfoot. All of these babies (ie, their parents), except 1,
      had moderate to poor compliance with the treatment protocol. CONCLUSIONS:
      Tenotomy as an office procedure using topical and local anesthesia is a safe
      procedure. It does not incur a substantial rate of readmission to the emergency
      room, either because of parental concern or because of actual complications. The
      need for retenotomy is related to a low compliance with the treatment protocol.
      LEVEL OF EVIDENCE: Level II.

PMID- 22584845
TI  - Intralesional methylprednisolone for painful solitary eosinophilic granuloma of
      the appendicular skeleton in children.
AB  - BACKGROUND: Previous case reports and small series have reported on the treatment
      of eosinophilic granuloma of bone. We present our long experience in a large
      group of children and teenagers with symptomatic eosinophilic granuloma of the
      appendicular skeleton to evaluate clinical and imaging outcome after
      methylprednisolone injection. METHODS: Sixty-six patients with symptomatic
      solitary eosinophilic granuloma of the appendicular skeleton treated by
      incisional or percutaneous biopsy and methylprednisolone injection were
      retrospectively studied. There were 38 boys and 28 girls (mean age, 7.2 y). The
      mean follow-up was 10.7 years (median, 11.2 y; range, 3 to 15 y). All patients
      presented with symptomatic lesions including pain or tenderness and fever and had
      1 intralesional injection of methylprednisolone acetate after biopsy: 52 patients
      had incisional biopsy and 14 patients had percutaneous computed tomography-guided
      biopsy. RESULTS: Complete resolution of symptoms was observed in 58 patients
      (92%) at 48 to 72 hours (50 patients) and in 7 days (8 patients) after the
      procedure. Complete imaging reconstitution of bone was observed in 60 patients
      (95.2%) at 1 to 2 years after the procedure. No patient had recurrence.
      Multifocal disease was diagnosed in 7 patients (11%) at 3 months to 6 years.
      Complications occurred in 2 patients: one patient with a clavicular lesion had a
      pathologic fracture after open direct methylprednisolone injection and the second
      patient developed trochanteric bursitis after computed tomography-guided
      methylprednisolone injection. CONCLUSIONS: Biopsy and direct intralesional
      methylprednisolone injection is safe for symptomatic eosinophilic granulomas of
      the appendicular skeleton in children with effective clinical and imaging
      resolution of the lesions.

PMID- 22584846
TI  - Rasch analysis of the pediatric outcomes data collection instrument in 720
      patients with cerebral palsy.
AB  - BACKGROUND: The pediatric outcomes data collection instrument (PODCI) was
      originally developed to carry out a functional assessment of children and
      adolescents (including patients with cerebral palsy), focusing on musculoskeletal
      health. Validated questionnaires are important for assessing the functional
      outcome of cerebral palsy, and are meant to have unidimensionality, proper item
      gap, no ceiling and floor effects, and no item redundancy. The advances in health
      measurements have led to the application of Rasch analysis to assess
      questionnaires. This study evaluated PODCI in patients with cerebral palsy using
      Rasch analyses. METHODS: The study included a total of 720 patients with gross
      motor function classification system level I to III, 192 with unilateral
      involvement and 528 with bilateral involvement. Rasch analysis was performed to
      obtain information on (1) the information weight fit statistic to assess the
      unidimensionality and redundancy of the items in each domain; (2) average item
      calibration to detect the item separation; and (3) item map to evaluate the
      ceiling and floor effects. RESULTS: The PODCI worked best in the sports/physical
      function domain. In information weight fit statistics, there were 4 items
      violating unidimensionality, which included "putting on his/her coat" in
      transfer/basic mobility and "getting together and do things with friends" in
      sports/physical function. There were 4 items with item redundancy. Inadequate
      item separation was observed in the transfer/basic mobility domain. A ceiling
      effect was found in all domains, except for the sports/physical function.
      CONCLUSIONS: The sports/physical function domain in PODCI generally satisfies the
      requirements of Rasch item response theory and is an appropriate measure of the
      function in cerebral palsy. Although some individual items do not fit well, the
      PODCI can be improved by eliminating the redundant items and by adding more
      difficult tasks to fill in the gaps. LEVEL OF EVIDENCE: Level II.

PMID- 22584847
TI  - Radius crossover sign:  an indication of malreduced radius shaft greenstick
      fractures.
AB  - BACKGROUND: Radius shaft greenstick fractures in children can be a challenging
      injury to treat because angulation and rotational alignment are difficult to
      assess. METHODS: In this report, we describe a simple method for analyzing the
      deformity and identifying rotational and angular malalignment. This technique
      involves analyzing the forearm radiographs as 2 segments, proximal and distal,
      and assuring that the rotational position of each matches the other. RESULTS: We
      present 3 cases of proximal radius greenstick fractures in malalignment to
      demonstrate the radius crossover sign. CONCLUSIONS: Identifying the radius
      crossover sign, and proceeding with further closed reduction may prevent
      deformity that could otherwise result in a significant loss of forearm motion.
      LEVEL OF EVIDENCE: Level V.

PMID- 22584848
TI  - Interleukin-10 of red nucleus plays anti-allodynia effect in neuropathic pain
      rats with spared nerve injury.
AB  - Our previous studies have shown that pro-inflammatory cytokines tumor necrosis
      factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in red nucleus (RN) are
      involved in the development of neuropathic pain and play facilitated roles on the
      mechanical allodynia induced by peripheral nerve injury. The current study was
      designed to evaluate the expression and effect of IL-10, an anti-inflammatory
      cytokine, in the RN of rats with spared nerve injury (SNI). Immunohistochemical
      staining results demonstrated when 3 weeks after SNI, the expression level of IL
      10 in the contralateral RN of SNI rats was apparently higher than those of sham
      operated and normal rats. To further study the effect of IL-10 in the development
      of neuropathic pain, different doses of IL-10 (1.0, 0.5 and 0.1 MUg/MUl) were
      microinjected respectively into the RN contralateral to the nerve injury side of
      SNI rats. Results demonstrated that higher doses of IL-10 (1.0 and 0.5 MUg/MUl)
      significantly attenuated the mechanical allodynia of neuropathic rats, while 0.1
      MUg/MUl of IL-10 did not show any analgesic effect. These results suggest that IL
      10 of RN participates in the development of neuropathic pain and plays inhibitory
      roles on the mechanical allodynia induced by SNI.

PMID- 22584849
TI  - SMARCE1 Promotes chicken embryonic gonad development by regulating ER alpha and
      AR expression.
AB  - SMARCE1 is one of some differentially expressed genes screened from a subtracted
      cDNA library between females and males during the period of sex differentiation.
      To understand the potential role of SMARCE1 in avian sex determination and
      differentiation, over-expression of SMARCE1 was performed in chicken embryos
      using the RCASBP.B retrovirus. Results showed that SMARCE1 expression was up
      regulated in the infected embryonic gonads at the investigated stages (E6.5
      E12.5) assessed by quantitative real-time RT-PCR, whole mount in situ
      hybridization and immunohistochemistry. With the over-expression of SMARCE1,
      CYP19A1, FOXL2, ERalpha, and SOX9 expression was significantly up-regulated while
      AR expression was significantly decreased in the male and/or female chicken
      gonad. Nevertheless, DMRT1 and AMH expression was not changed after the over
      expression of SMARCE1. It is proposed that it might be via the SMARCE1-FOXL2
      pathway that CYP19A1 expression was activated, and DMRT1 expression may be
      independent of the SMARCE1-SOX9 pathway. Meanwhile, the SMARCE1-AR pathway might
      be antagonized by up-regulated expression of ERalpha via estrogen-ER/androgen-AR
      signaling. The results of HE staining showed that the ovarian cortex was
      thickened and both testis seminiferous cord and interstitial cells were increased
      with the over-expression of SMARCE1. In conclusion, SMARCE1 can promote chicken
      embryonic gonad development by regulating the ERalpha and AR expression.

PMID- 22584850
TI  - Visceral leishmaniasis infection in a refractory multiple myeloma patient treated
      with bortezomib.

PMID- 22584851
TI  - B cell non-Hodgkin's lymphoma: experience from a tertiary care cancer center.
AB  - Information on presentation and outcome of B cell non-Hodgkin's lymphoma (B-NHL)
      is limited from developing countries. Data of newly diagnosed adult aggressive B
      NHL (n = 260) patients were analyzed for clinical presentation, histological
      subtype, response to therapy, and survival. Univariate and multivariate Cox
      regression analyses were performed for identification of prognostic factors.
      Diffuse large B cell lymphoma was the most common subtype (71 %). Median age was
      50 years (18-78 years). The most common symptom was peripheral lymphadenopathy
      seen in 66 % of cases. Forty-seven percent of patients had advanced stage (stage
      III/IV), and 41 % had ECOG performance status of II-IV. B symptoms and bulky
      disease were present in 47 and 26 %, respectively. Intermediate to high risk
      score according to the International Prognostic Index (IPI) was seen in 67 %.
      Cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP) and CHOP-like
      regimens were used in 70 % cases, while R-CHOP was used in 18 % cases. For
      diffuse large B cell lymphoma (DLBCL) patients, in intent-to-treat analysis, the
      overall response and complete remission rates were 73 and 60 %, respectively.
      Four-year event-free and overall survival was 54 and 64.7 %, respectively.
      Presence of B symptoms (p = 0.004), stage III/IV (p = 0.02/p = 0.01), performance
      status II-IV (p = 0.001), serum albumin (<4 g/dl; p = 0.001), hemoglobin <10 g/dl
      (p = 0.001), high-risk IPI score (0.001), use of <6 chemotherapy cycles (p =
      0.001), and failure to attain CR (p = 0.001) were significantly associated with
      lower event-free and overall survival. DLBCL is the most common B cell NHL seen
      at our center. Intermediate to high IPI was seen in 45 % and was associated with
      poor survival. Majority of the patients were treated without rituximab. In
      comparison to western data, we observed higher proportion of DLBCL, lower median
      age, higher male to female ratio, and higher proportion of patients with B
      symptoms in our study.

PMID- 22584852
TI  - [Obstetric ultrasound in Brazil: a plea for standardization].

PMID- 22584853
TI  - [Serous and non-serous ovarian carcinoma: histological tumor type as related to
      the grade of differentiation and disease prognosis].
AB  - PURPOSE: To compare the clinical-pathological features of women with serous and
      non-serous ovarian tumors and to identify the factors associated with survival.
      METHODS: In this reconstructed cohort study, 152 women with ovarian carcinoma,
      who attended medical consultations between 1993 and 2008 and who were followed-up
      until 2010 were included. The histological type was clearly established for all
      women: 81 serous carcinomas and 71 non-serous tumors (17 endometrioid, 44
      mucinous and 10 clear cell carcinomas). The crude and adjusted odds ratios (OR),
      with the respective 95% confidence intervals (95%CI), were calculated for the
      clinical and pathological features, comparing serous and non-serous histological
      types. The Hazard Ratios (HR) with 95%CI was calculated for overall survival,
      considering the clinical and pathological features. RESULTS: Comparison of serous
      to non-serous tumor types by univariate analysis revealed that serous tumors were
      more frequently found in postmenopausal women, and were predominantly high
      histological grade (G2 and G3), advanced stage, with CA125>250 U/mL, and with
      positive peritoneal cytology. After multivariate regression, the only association
      remaining was that of high histological grade with serous tumors (adjusted OR
      15.1; 95%CI 2.9-77.9). We observed 58 deaths from the disease. There was no
      difference in overall survival between women with serous carcinoma and women with
      non-serous carcinoma (HR 0.4; 95%CI 0.1 - 1.1). It was observed that women aged
      50 years or less (HR 0.4; 95%CI 0.1-0.9) and those who were in menacne (HR 0.3;
      95%CI 0.1-0.9) had a longer survival compared respectively to those above 50
      years of age and menopaused. High histological grade (G2 and G3) (p<0.01), stages
      II-IV (p<0.008) and positive cytology (p<0.001) were significantly associated
      with worse prognosis. CA125 and the presence of ascites did not correlate with
      survival. Survival was poor when the disease was diagnosed in stages II to IV and
      compared to stage I (log-rank p<0.01) regardless of histological type (serous and
      non-serous). CONCLUSIONS: The proportion of high histological grade (G2 and G3)
      was significantly higher among serous than non-serous carcinomas. Serous and non
      serous histological types were not related to overall survival.

PMID- 22584854
TI  - [Apparently matured oocytes injected in telophase I have worse outcomes from
      assisted reproduction].
AB  - PURPOSE: To evaluate the nuclear maturation stage and the presence of meiotic
      spindles of in vivo matured oocytes from infertile women undergoing stimulated
      cycles for intracytoplasmic sperm injection (ICSI) and compare intracytoplasmic
      sperm injection outcomes between oocytes in telophase I (TI) and metaphase II
      (MII), and the ones with and without visible meiotic spindle. METHODS: A
      prospective and controlled study with 106 infertile patients who underwent
      ovarian stimulation for intracytoplasmic sperm injection purposes. Patients aged
      38 years or less, with basal follicle stimulating hormone (FSH) less than 10
      mIU/mL and body mass index (BMI) less than 30 kg/m2. Were included patients
      presenting any systemic diseases, any active infection, smokers or patients who
      had been using hormonal medications and hormonal and nonhormonal anti
      inflammatory drugs for the past two months prior to the assisted reproduction
      procedure were excluded. The oocytes with the first polar body extruded (in vivo
      matured oocytes) were imaged by polarization microscopy immediately before
      intracytoplasmic sperm injection and characterized according to nuclear
      maturation stage (telophase I and metaphase II) and to the presence of a meiotic
      spindle. We analyzed the fertilization rates, cleavage, number of good quality
      embryos on the second day (D2) from oocytes on telophase I versus those in
      metaphase II, and metaphase II visible spindle versus non-visible ones. Data were
      analyzed comparatively by Fisher's exact test. The level of significance was set
      at 5% in all analyses (p<0.05). RESULTS: The meiotic spindles of 516 oocytes were
      imaged using polarization microscopy. From the 516 oocytes analyzed, seventeen
      were in telophase I (3.3%) and 499 (96.7%) in metaphase II. The oocytes injected
      in telophase I had significantly lower fertilization rates than those injected in
      metaphase II (53 and 78%, respectively) and produced no good quality embryos on
      day 2. When the oocytes with and without a visible meiotic spindle were compared,
      there was no significant difference in the intracytoplasmic sperm injection
      results. CONCLUSIONS: Oocytes injected in telophase I showed lower fertilization
      rates when compared to those in metaphase II. It is possible that the analysis of
      oocyte nuclear maturation by polarization microscopy can be used as a predictor
      of fertilization after intracytoplasmic sperm injection.

PMID- 22584855
TI  - [Comparative study between the pH test and of the KOH versus Nugent score for
      diagnosis of bacterial vaginosis in pregnant women].
AB  - PURPOSE: To assess the prevalence of bacterial vaginosis and to compare the
      accuracy of testing pH and KOH with the Nugent gradient, the gold standard for
      the diagnosis of bacterial vaginosis (BV) in asymptomatic and symptomatic
      pregnant women at low risk. METHODS: We conducted a cross-sectional study on 321
      pregnant women with gestational age between 14 and 26 weeks, 218 of them
      asymptomatic and 103 with vaginal complaints suggestive of bacterial vaginosis.
      All women were assessed by the criteria of Nugent and subjected to the
      measurement of vaginal pH and to the 10% KOH test. The Kappa coefficient was used
      to evaluate the methods in terms of diagnostic agreement. RESULTS: Most patients
      were adolescents (mean age 21.0 +/- 5.6 years), nulliparous and mulattos. The
      prevalence of bacterial vaginosis was 33.3% as estimated by the pH and KOH method
      and 35.5% by the Nugent method. Excellent agreement of the methods was found
      among asymptomatic pregnant women, with 72.5% of them showing negative results to
      both tests, which resulted in a high Kappa coefficient (k=0.82). The group of
      symptomatic women showed 49.5% positivity to both diagnostic methods, with
      excellent agreement (k=0.74). CONCLUSION: The prevalence of bacterial vaginosis
      determined by both the pH and KOH method and the Nugent score was high. The pH
      and KOH method can diagnose bacterial vaginosis as accurately as the Nugent
      criterion.

PMID- 22584856
TI  - [Morbidity and associated factors in climacteric women: a population based study
      in women with 11 or more years of formal education].
AB  - PURPOSE: To evaluate factors associated with morbidities among Brazilian women
      aged 40-65 years and with 11 or more years of schooling. METHODS: A secondary
      analysis of a cross-sectional population-based study was conducted, using an
      anonymous self-report questionnaire completed by 377 women. Were evaluated, with
      this instrument, some morbidities (hypertension, diabetes, insomnia and
      depression) and sociodemographic, behavioral, clinical and reproductive factors.
      The association between morbidities and independent variables was evaluated by
      the chi2 test. Multiple logistic regression analysis with stepwise selection
      criteria was used to select the major factors associated with morbid conditions.
      RESULTS: In the multiple regression analysis, insomnia was associated with
      bad/fair self-perception of health (OR=2.3) and nervousness (OR=5.1). Depression
      was associated with bad/fair self-perception of health (OR=3.7) and bad/poor
      leisure (OR=2.8). Hypertension was associated with obesity (OR=3.1) and being in
      postmenopausal (OR=2.6). Diabetes was associated with age above 50 years (OR=3.9)
      and obesity (OR=12.5). CONCLUSIONS: The prevalence of morbidities was high and a
      worse self-perception of health and obesity were the main factors associated with
      morbidity.

PMID- 22584857
TI  - [Ultrasound evaluation of uterine scar after segmental transverse cesarean
      surgery].
AB  - PURPOSE: To evaluate the thickness of the lower uterine segment by transvaginal
      ultrasound in a group of non-pregnant women and to describe the morphologic
      findings in the scar of those submitted to cesarean section. METHODS: A
      retrospective study of 155 transvaginal ultrasound images obtained from
      premenopausal and non-pregnant women, conducted between January 2008 and November
      2011. the subjects were divided into three groups: women who were never pregnant
      (Control Group I), women with previous vaginal deliveries (Control Group II) and
      women with previous cesarean section (Observation Group). We excluded women with
      a retroverted uterus, intrauterine device users, pregnant women and those with
      less than one year of tsince the last obstetrical event. The data were analyzed
      statistically with Statistica, version 8.0 software. ANOVA and LSD were used to
      compare the groups regarding quantitative variables and the Student's t-test was
      used to compare the thickness of the anterior and posterior isthmus. The Spearman
      correlation coefficient was calculated to estimate the association between
      quantitative variables. P values <0.05 were considered statistically significant.
      RESULTS: There was significant difference between the thickness of the anterior
      and posterior isthmus only in the group of women with previous cesarean section.
      Comparing the groups two by two, no significant differences between the thickness
      of the anterior and posterior isthmus were observed in the Control Groups, but
      this difference was significant when we compared the Observation Group with each
      Control Group. In the Observation Group, no correlation was found between the
      thickness of the isthmus and the number of previous cesarean deliveries or the
      time elapsed since the last birth. A niche was found in the cesarean scar in
      30.6% of the women in the Observation Group, 93% of whom complained of post
      menstrual bleeding. CONCLUSION: The relationship between the thickness of the
      anterior and posterior wall of the lower uterine segment by transvaginal
      ultrasound is a suitable method for the evaluation of the uterine lower segment
      in women with previous cesarean sections.

PMID- 22584858
TI  - [Photoprotection, melasma and quality of life in pregnant women].
AB  - PURPOSE: To evaluate habits of sun exposure and sun protection of pregnant women
      in a public hospital, to assess orientation about photo protection during the
      prenatal care, and to detect the presence of melasma and its impact on their
      quality of life. METHODS: A descriptive cross sectional study conducted among
      women of 18 years old and older, after delivery, who participated in a program of
      prenatal care in the South Region of Brazil. The sample was non-probabilistic by
      convenience. Data collection occurred from July to August 2011 through direct
      interview using a structured questionnaire to obtain personal information and
      photo protection habits during pregnancy, skin assessment and photographic record
      of lesions through informed consent. The skin was classified per Fitzpatrick's
      phototypes and the melasma was diagnosed clinically. In the patients with
      melasma, the MELASQoL-PB version was applied. The analysis was performed using
      Statistica, version 8.0, and the significance level of p<0.05. RESULTS: In the
      sample (109 mothers) predominated white women (60.6% phototype III), young
      (average age 24.4 years SD=6.1) and housewives (59.6%). The majority (80%) stayed
      exposed to sunlight for 1-2 hours per day between 10 am and 3 pm, and from those
      (72%) did not apply any photoprotection due to lack of sunscreen habit. Other
      physical means of sun protection were used by 15% of these patients. Information
      during prenatal care about the risks of sun exposure was reported by 34% of the
      mothers interviewed. There was a trend toward a significant association between
      prenatal guidance and daily use of sunscreen (p=0.088). About 20% of mothers had
      melasma. The average score MELASQol-PB (25) showed a negative impact on quality
      of life of these patients. CONCLUSION: In these women, sun exposure occurred at
      inappropriate times, without proper guidance and without the use of an effective
      sunscreen. The mothers with melasma complained about the appearance of their
      skin, frustration and embarrassment.

PMID- 22584859
TI  - [Survival and morbidity of premature babies with less than 32 weeks of gestation
      in the central region of Brazil].
AB  - PURPOSE: To evaluate the survival and complications associated with prematurity
      of infants with less than 32 weeks of gestation. METHODS: It was done a
      prospective cohort study. All preterm infants with a gestational age between 25
      and 31 weeks and 6 days, born alive without congenital anomalies and admitted to
      the NICU between August 1st, 2009 and October 31st, 2010 were included. Newborns
      were stratified into three groups: G25, 25 to 27 weeks and 6 days; G28, 28 to 29
      weeks and 6 days; G30, 30 to 31 weeks and 6 days, and they were followed up to 28
      days. Survival at 28 days and complications associated with prematurity were
      evaluated. Data were analyzed statistically by c2 test, analysis of variance,
      Kruskal-Wallis test, odds ratio with confidence interval (CI) and multiple
      logistic regression, with significance set at 5%. RESULTS: The cohort comprised
      198 preterm infants (G25=59, G28=43 and G30=96). The risk of death was
      significantly higher in G25 and G28 compared to G30 (RR=4.14, 95%CI 2.23-7.68 and
      RR=2.84, 95%CI: 1.41-5.74). Survival was 52.5%, 67.4% and 88.5%, respectively.
      Survival was greater than 50% in preterm >26 weeks and birth weight >700 g.
      Neonatal morbidity was inversely proportional to gestational age, except for
      necrotizing enterocolitis and leukomalacia, which did not differ among groups.
      Logistic regression showed that pulmonary hemorrhage (OR=3.3, 95%CI 1.4-7.9) and
      respiratory distress syndrome (OR=2.5, 95%CI 1.1-6.1) were independent risk
      factors for death. There was a predominance of severe hemorrhagic brain lesions
      in G25. CONCLUSION: Survival above 50% occurred in infants with a gestational age
      of more than 26 weeks and >700 g birth weight. Pulmonary hemorrhage and
      respiratory distress syndrome were independent predictors of neonatal death. It
      is necessary to identify the best practices to improve the survival of extreme
      preterm infants.

PMID- 22584864
TI  - Pharmacological treatment of schizophrenia: a critical review of the pharmacology
      and clinical effects of current and future therapeutic agents.
AB  - Since the introduction of chlorpromazine and throughout the development of the
      new-generation antipsychotic drugs (APDs) beginning with clozapine, the D(2)
      receptor has been the target for the development of APDs. Pharmacologic actions
      to reduce neurotransmission through the D(2) receptor have been the only proven
      therapeutic mechanism for psychoses. A number of novel non-D(2) mechanisms of
      action of APDs have been explored over the past 40 years but none has
      definitively been proven effective. At the same time, the effectiveness of
      treatments and range of outcomes for patients are far from satisfactory. The
      relative success of antipsychotics in treating positive symptoms is limited by
      the fact that a substantial number of patients are refractory to current
      medications and by their lack of efficacy for negative and cognitive symptoms,
      which often determine the level of functional impairment. In addition, while the
      newer antipsychotics produce fewer motor side effects, safety and tolerability
      concerns about weight gain and endocrinopathies have emerged. Consequently, there
      is an urgent need for more effective and better-tolerated antipsychotic agents,
      and to identify new molecular targets and develop mechanistically novel compounds
      that can address the various symptom dimensions of schizophrenia. In recent
      years, a variety of new experimental pharmacological approaches have emerged,
      including compounds acting on targets other than the dopamine D(2) receptor.
      However, there is still an ongoing debate as to whether drugs selective for singe
      molecular targets (that is, 'magic bullets') or drugs selectively non-selective
      for several molecular targets (that is, 'magic shotguns', 'multifunctional drugs'
      or 'intramolecular polypharmacy') will lead to more effective new medications for
      schizophrenia. In this context, current and future drug development strategies
      can be seen to fall into three categories: (1) refinement of precedented
      mechanisms of action to provide drugs of comparable or superior efficacy and side
      effect profiles to existing APDs; (2) development of novel (and presumably non
      D(2)) mechanism APDs; (3) development of compounds to be used as adjuncts to APDs
      to augment efficacy by targeting specific symptom dimensions of schizophrenia and
      particularly those not responsive to traditional APD treatment. In addition,
      efforts are being made to determine if the products of susceptibility genes in
      schizophrenia, identified by genetic linkage and association studies, may be
      viable targets for drug development. Finally, a focus on early detection and
      early intervention aimed at halting or reversing progressive pathophysiological
      processes in schizophrenia has gained great influence. This has encouraged future
      drug development and therapeutic strategies that are neuroprotective. This
      article provides an update and critical review of the pharmacology and clinical
      profiles of current APDs and drugs acting on novel targets with potential to be
      therapeutic agents in the future.

PMID- 22584865
TI  - Striatal morphology as a biomarker in neurodegenerative disease.
AB  - The striatum, comprising the caudate nucleus, putamen and nucleus accumbens,
      occupies a strategic location within cortico-striato-pallido-thalamic-cortical
      (corticostriatal) re-entrant neural circuits. Striatal neurodevelopment is
      precisely determined by phylogenetically conserved homeobox genes. Consisting
      primarily of medium spiny neurons, the striatum is strictly topographically
      organized based on cortical afferents and efferents. Particular corticostriatal
      neural circuits are considered to subserve certain domains of cognition, emotion
      and behaviour. Thus, the striatum may serve as a map of structural change in the
      cortical afferent pathways owing to deafferentation or neuroplasticity, and
      conversely, structural change in the striatum per se may structurally disrupt
      corticostriatal pathways. The morphology of the striatum may be quantified in
      vivo using advanced magnetic resonance imaging, as may cognitive functioning
      pertaining to corticostriatal circuits. It is proposed that striatal morphology
      may be a biomarker in neurodegenerative disease and potentially the basis of an
      endophenotype.

PMID- 22584866
TI  - Evaluating risk loci for schizophrenia distilled from genome-wide association
      studies in Han Chinese from Central China.

PMID- 22584868
TI  - Linking in vivo brain serotonin type 1B receptor density to phenotypic
      heterogeneity of posttraumatic stress symptomatology.

PMID- 22584869
TI  - Prefrontal synaptic markers of cocaine addiction-like behavior in rats.
AB  - Defining the drug-induced neuroadaptations specifically associated with the
      behavioral manifestation of addiction is a daunting task. To address this issue,
      we used a behavioral model that differentiates rats controlling their drug use
      (Non-Addict-like) from rats undergoing transition to addiction (Addict-like).
      Dysfunctions in prefrontal cortex (PFC) synaptic circuits are thought to be
      responsible for the loss of control over drug taking that characterizes addicted
      individuals. Here, we studied the synaptic alterations in prelimbic PFC (pPFC)
      circuits associated with transition to addiction. We discovered that some of the
      changes induced by cocaine self-administration (SA), such as the impairment of
      the endocannabinoid-mediated long-term synaptic depression (eCB-LTD) was
      similarly abolished in Non-Addict- and Addict-like rats and thus unrelated to
      transition to addiction. In contrast, metabotropic glutamate receptor 2/3
      mediated LTD (mGluR2/3-LTD) was specifically suppressed in Addict-like rats,
      which also show a concomitant postsynaptic plasticity expressed as a change in
      the relative contribution of AMPAR and NMDAR to basal glutamate-mediated synaptic
      transmission. Addiction-associated synaptic alterations in the pPFC were not
      fully developed at early stages of cocaine SA, when addiction-like behaviors are
      still absent, suggesting that pathological behaviors appear once the pPFC is
      compromised. These data identify specific synaptic impairments in the pPFC
      associated with addiction and support the idea that alterations of synaptic
      plasticity are core markers of drug dependence.

PMID- 22584870
TI  - Idiopathic pulmonary fibrosis is associated with circulating antiepithelial
      antibodies.
AB  - PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a restrictive fibrotic lung
      disease of uncertain etiology. Alveolar epithelial injury may be one of the
      inciting triggers in the pathogenesis of this disorder. We hypothesized that
      circulating antibodies to alveolar epithelial and endothelial cells may be
      involved in the pathogenesis of IPF. METHODS: Antibodies to alveolar epithelial
      and endothelial cells were analyzed by indirect immunofluorescence using alveolar
      epithelial cells (A549) and human umbilical vein endothelial cells respectively.
      IgG and IgM antibodies in patients' serum were evaluated. Patterns of
      immunofluorescence, including membranous, cytoplasmic, and nuclear staining, were
      analyzed by fluorescence microscopy. The severity of immunofluorescence was
      divided into mild, moderate, and severe categories. Fifty-six patients (IPF = 28,
      non-IPF ILD = 9, non-ILD control = 19) were evaluated for antiepithelial
      antibodies, and 28 patients (IPF = 12, non-IPF ILD = 3, non-ILD control = 13)
      were studied for antiendothelial antibodies. RESULTS: Compared with control
      subjects, serum from IPF patients displayed significantly higher IgG binding to
      alveolar epithelial cells (P = 0.041) with a membranous pattern of
      immunofluorescence. However, there was no significant difference in
      immunofluorescence with IgG on endothelial cells (P = 0.165). In terms of IgM
      antibodies, there was no differential fluorescence observed for either epithelial
      or endothelial cells. CONCLUSIONS: There is evidence of increased IgG antibodies
      directed against alveolar epithelium in IPF. These antibodies may play a
      significant role in the pathogenesis of this fibrotic disorder. The findings of
      this study suggest further evaluation of the role of immune mediated alveolar
      epithelial injury in IPF.

PMID- 22584871
TI  - ALK-mutated non-small-cell lung cancer: a new strategy for cancer treatment.
AB  - The anaplastic lymphoma kinase (ALK) tyrosine kinase (TK) receptor has emerged
      recently as a potentially relevant biomarker and therapeutic target in solid and
      hematologic tumors. A variety of alterations in the ALK gene, such as mutations,
      overexpression, amplification, translocations, or other structural
      rearrangements, have been implicated in human cancer tumorigenesis. In this
      article we review the potential role that ALK may have in lung tumor origin, the
      methodology to detect the different molecular alterations, and the most important
      clinical aspects of ALK alterations in NSCLC patients.

PMID- 22584867
TI  - Convergent functional genomics of schizophrenia: from comprehensive understanding
      to genetic risk prediction.
AB  - We have used a translational convergent functional genomics (CFG) approach to
      identify and prioritize genes involved in schizophrenia, by gene-level
      integration of genome-wide association study data with other genetic and gene
      expression studies in humans and animal models. Using this polyevidence scoring
      and pathway analyses, we identify top genes (DISC1, TCF4, MBP, MOBP, NCAM1,
      NRCAM, NDUFV2, RAB18, as well as ADCYAP1, BDNF, CNR1, COMT, DRD2, DTNBP1, GAD1,
      GRIA1, GRIN2B, HTR2A, NRG1, RELN, SNAP-25, TNIK), brain development, myelination,
      cell adhesion, glutamate receptor signaling, G-protein-coupled receptor signaling
      and cAMP-mediated signaling as key to pathophysiology and as targets for
      therapeutic intervention. Overall, the data are consistent with a model of
      disrupted connectivity in schizophrenia, resulting from the effects of
      neurodevelopmental environmental stress on a background of genetic vulnerability.
      In addition, we show how the top candidate genes identified by CFG can be used to
      generate a genetic risk prediction score (GRPS) to aid schizophrenia diagnostics,
      with predictive ability in independent cohorts. The GRPS also differentiates
      classic age of onset schizophrenia from early onset and late-onset disease. We
      also show, in three independent cohorts, two European American and one African
      American, increasing overlap, reproducibility and consistency of findings from
      single-nucleotide polymorphisms to genes, then genes prioritized by CFG, and
      ultimately at the level of biological pathways and mechanisms. Finally, we
      compared our top candidate genes for schizophrenia from this analysis with top
      candidate genes for bipolar disorder and anxiety disorders from previous CFG
      analyses conducted by us, as well as findings from the fields of autism and
      Alzheimer. Overall, our work maps the genomic and biological landscape for
      schizophrenia, providing leads towards a better understanding of illness,
      diagnostics and therapeutics. It also reveals the significant genetic overlap
      with other major psychiatric disorder domains, suggesting the need for improved
      nosology.

PMID- 22584873
TI  - Genetic variation in the neuropeptide Y gene promoter is associated with
      increased risk of tobacco smoking.
AB  - BACKGROUND: Neuropeptide Y (NPY) is a strong candidate gene regarding the
      pathophysiology of tobacco dependence. It has been associated with various
      addictive and psychiatric disorders, and closely interacts with the brain reward
      system. The aim of the present study was to test for association between a
      functional genetic variant in the NP-Y promoter gene (SNP rs16147) and tobacco
      smoking. METHODS: In a population-based case-control multicenter study designed
      for tobacco addiction research, a total of 550 Caucasian current smokers, and 544
      never-smokers were genotyped for SNP rs16147 and behaviorally characterized with
      the State-Trait Anxiety Inventory (STAI). RESULTS: Subjects with TT genotype of
      the SNP rs16147 were significantly more frequently smokers than never-smokers (p
      = 0.046). In addition, TT genotype exhibited increased state anxiety scores
      compared to carriers of the C allele (p = 0.037). CONCLUSIONS: Our results
      provide evidence for an involvement of the functionally relevant SNP rs16147 in
      the pathophysiology of tobacco dependence. Further studies are needed to confirm
      our findings.

PMID- 22584872
TI  - Quantification, self-renewal, and genetic tracing of FL1+ tumor-initiating cells
      in a large cohort of human gliomas.
AB  - Evidence has emerged that the initiation and growth of gliomas is sustained by a
      subpopulation of cancer-initiating cells (CICs). Because of the difficulty of
      using markers to tag CICs in gliomas, we have previously exploited more robust
      phenotypic characteristics, including a specific morphology and intrincic
      autofluorescence, to identify and isolate a subpopulation of glioma CICs, called
      FL1(+). The objective of this study was to further validate our method in a large
      cohort of human glioma and a mouse model of glioma. Seventy-four human gliomas of
      all grades and the GFAP-V(12)HA-ras B8 mouse model were analyzed for in vitro
      self-renewal capacity and their content of FL1(+). Nonneoplastic brain tissue and
      embryonic mouse brain were used as control. Genetic traceability along passages
      was assessed with microsatellite analysis. We found that FL1(+) cells from low
      grade gliomas and from control nonneoplasic brain tissue show a lower level of
      autofluorescence and undergo a restricted number of cell divisions before dying
      in culture. In contrast, we found that FL1(+) cells derived from many but not all
      high-grade gliomas acquire high levels of autofluorescence and can be propagated
      in long-term cultures. Moreover, FL1(+) cells show a remarkable traceability over
      time in vitro and in vivo. Our results show that FL1(+) cells can be found in all
      specimens of a large cohort of human gliomas of different grades and in a model
      of genetically induced mouse glioma as well as nonneoplastic brain. However,
      their self-renewal capacity is variable and seems to be dependent on the tumor
      grade.

PMID- 22584874
TI  - What do Kramer's Baby-Friendly Hospital Initiative PROBIT studies tell us? A
      review of a decade of research.
AB  - BACKGROUND: Kramer et al's PROBIT (Promotion of Breastfeeding Intervention Trial)
      research in Belarus studied effects of the Baby-Friendly Hospital Initiative
      (BFHI) training on breastfeeding duration, exclusivity, and health outcomes.
      AIMS: To critique inclusion criteria, context, approaches to data analysis, and
      health outcome results. METHOD: Twenty-two articles were retrieved from PubMed
      and the PROBIT Website for 2001-2010; 6 were excluded as not focusing on
      breastfeeding and health outcomes. RESULTS: PROBIT data from the cluster
      randomized hospital comparisons included only breastfed babies since all non
      breastfed babies were excluded from the research. Context may affect outcomes,
      knowing that Belarus has good basic health services, 3-year maternity leaves with
      little use of daycare, 95% breastfeeding initiation rate, and a well-educated
      population. PROBIT data were analyzed in 2 ways: (a) intent-to-treat analyses of
      breastfeeding and health differences by cluster randomized intervention and
      control site mother/baby pairs; and (b) as an observational cohort study of
      health outcomes for all mother/baby pairs, analyzed by various breastfeeding
      categorizations and controlling for biases. PROBIT demonstrated links between
      BFHI and longer breastfeeding duration (19.7% vs 11.4% at 12 months, P < .001)
      and exclusivity (43.3% vs 6.4% at 3 months, P < .001), reductions in
      gastrointestinal episodes and rashes, higher verbal IQ scores, and longer
      exclusive breastfeeding rates for subsequent children but no statistically
      significant differences in the child's body mass index, blood pressure, or dental
      health. CONCLUSION: PROBIT provides foundational evidence for BFHI policy and
      follow-up care. Knowing that non-breastfed babies were excluded, caution must be
      exercised for health comparisons.

PMID- 22584875
TI  - Are you Baby-Friendly? Knowledge deficit among US maternity staff.
AB  - BACKGROUND: The Baby-Friendly Hospital Initiative began in 1991. In 2010,
      approximately 3% of United States (US) hospitals were Baby-Friendly certified.
      When collecting data for related studies, we noted that many maternity staff
      erroneously claimed their hospital was Baby-Friendly.TM OBJECTIVE: To determine
      whether maternity staff in US hospitals could accurately describe their
      institution's status with regard to Baby-Friendly certification. METHODS: In 2010
      2011, we called all maternity hospitals in the US and asked to be connected to
      the maternity service. We then asked the person answering the maternity service
      phone: "Is your hospital a Baby-Friendly hospital?" and recorded the position of
      the respondent. RESULTS: We called 2974 hospitals, and received answers on Baby
      Friendly status from 2851. According to the Baby-Friendly USA Website
      (http://www.babyfriendlyusa.org), 3% (75/2851) of these hospitals were Baby
      Friendly. However, staff at 62% (1780/2851) stated their hospital was Baby
      Friendly. Staff at 15% (424/2851) did not know what the caller meant by "Baby
      Friendly hospital." Accuracy of knowledge varied dependent on the respondent's
      job title (P < .001). International Board Certified Lactation Consultants were
      most likely to be accurate, with 89% answering correctly. There was a strong
      positive correlation between the proportion of Baby-Friendly hospitals and the
      proportion of correct responses by state (r = 0.62, P < .001). CONCLUSION:
      Although the Baby-Friendly Hospital Initiative was established over 20 years ago,
      most US maternity staff responding to a telephone survey either incorrectly
      believed their hospital to be Baby-Friendly certified or were unaware of the
      meaning of "Baby-Friendly hospital."

PMID- 22584876
TI  - Changes in the heme ligation during folding of a Geobacter sulfurreducens sensor
      GSU0935.
AB  - Ligand binding and substitution reactions are important for metalloprotein
      folding and function. The heme sensor of a methyl-accepting chemotaxis GSU0935 is
      a c-type cytochrome from the bacterium Geobacter sulfurreducens. The heme domain
      switches one of its axial ligands from H(2)O to a low-spin ligand, presumably
      Met, upon reduction. The study analyzes the stability and folding kinetics of the
      ferric domain. Guanidine hydrochloride denaturation yields the low-spin heme
      species arising from coordination of the ferric heme by non-native His residues.
      The population of the low-spin species further increases and then declines during
      protein refolding. Kinetics and mutational effects suggest that His54, from the N
      terminal region of the domain, is the transient ligand to the heme. The capture
      and release of a non-native ligand within the compact partially-folded structures
      illustrates the flexibility of the heme environment in GSU0935, which may relate
      to the domain sensor function.

PMID- 22584878
TI  - Perceptions of health information exchange in home healthcare.
AB  - The aim of this study was to understand home healthcare nurses' current
      experiences in obtaining outside clinical information at the point of care and
      the type of clinical information they most desire in their patients' health
      information exchange profile. A Web-based survey was deployed to home health
      workers in New York to learn about their experiences retrieving outside clinical
      data prior to having access to health information exchange, preferred data
      elements and sources in their patients' health information exchange profiles, and
      how availability of outside clinical data may affect emergency department
      referrals. Of the 2383 participants, 566 responded for a 23.8% overall response
      rate, and 469 of these respondents were RNs. Most RNs, 96.7%, agreed that easier
      and quicker access to outside information would benefit delivery of care, and
      72.6% said the number of emergency department referrals would decrease. When
      asked about pre-health information exchange access to patient data, 96.3% said it
      was problematic. Inpatient discharge summaries were chosen most often by the RNs
      as a top five desired data element 81.5% of the time. Obtaining outside clinical
      information has been a challenge without health information exchange, but
      improved access to this information may lead to improved care. Further study is
      required to assess experiences with the use of health information exchange.

PMID- 22584877
TI  - Impact of weed control on arbuscular mycorrhizal fungi in a tropical
      agroecosystem: a long-term experiment.
AB  - Cover crop species represent an affordable and effective weed control method in
      agroecosystems; nonetheless, the effect of its use on arbuscular mycorrhizal
      fungi (AMF) has been scantily studied. The goal of this study was to determine
      root colonization levels and AMF species richness in the rhizosphere of maize
      plants and weed species growing under different cover crop and weed control
      regimes in a long-term experiment. The treatment levels used were (1) cover of
      Mucuna deeringian (Muc), (2) "mulch" of Leucaena leucocephala (Leu), (3) "mulch"
      of Lysiloma latisiliquum (Lys), (4) herbicide (Her), (5) manual weeding (CD), (6)
      no weeding (SD), and (7) no maize and no weeding (B). A total of 18 species of
      AMF belonging to eight genera (Acaulospora, Ambispora, Claroideoglomus,
      Funneliformis, Glomus, Rhizophagus, Sclerocystis, and Scutellospora) were
      identified from trap cultures. Muc and Lys treatments had a positive impact on
      AMF species richness (11 and seven species, respectively), while Leu and B
      treatments on the other hand gave the lowest richness values (six species each).
      AMF colonization levels in roots of maize and weeds differed significantly
      between treatment levels. Overall, the use of cover crop species had a positive
      impact on AMF species richness as well as on the percentage of root colonized by
      AMF. These findings have important implications for the management of traditional
      agroecosystems and show that the use of cover crop species for weed control can
      result in a more diverse AMF community which should potentially increase crop
      production in the long run.

PMID- 22584879
TI  - Factors related to the prevention and management of pressure ulcers.
AB  - Pressure ulcers (a type of skin failure) have served as an indicator of care
      quality. The purpose of this study was to utilize data-mining techniques as a
      means of identifying risk factors related to different stages of pressure ulcers
      to demonstrate how this means of analysis might be used as a vehicle to guide
      improved care quality. Data were obtained from a Web-based incident reporting
      system at a regional hospital in Taiwan. A total of 4301 cases dating from March
      2005 to May 2009 were collected. For data-cleaning purposes, data within 3 SDs
      were kept for further analysis. Data-mining techniques were applied to identify
      the predictors, and a logistic regression analysis was used for result comparison
      purposes. The results revealed that sacral ulcer was the most prevalent, and most
      ulcers were in stage I, followed by stages II to IV. Five predictors were
      identified including hemoglobin, weight, sex, height, and use of repositioning
      sheet. The study concluded that nurses could use data-mining technique to
      identify predictors to assist in guiding ulcer interventions such as those based
      on a patient's demographic profile and application of a repositioning sheet to
      prevent ulcer occurrence to minimize harm.

PMID- 22584880
TI  - A comparison of nurse attitudes before implementation and 6 and 18 months after
      implementation of an electronic health record.
AB  - The implementation of an electronic health record is a dramatic change in a
      healthcare organization; however, little is known about how nurse attitudes
      toward the electronic health record change over time. The purpose of this
      research project was to compare nurses' attitudes before and at 6 and 18 months
      after implementation of a comprehensive electronic health record. A presurvey
      postsurvey design using a modified Nurses' Attitudes Toward Computerization
      Questionnaire was implemented with a population of nurses employed at an academic
      medical center. On average, the nurses' attitude about the electronic health
      record became less positive between preimplementation (n = 312) and 6 months
      after implementation (n = 410) (74.2 vs 65.9, P < .0001) and preimplementation
      and 18 months after implementation (n = 262) groups (74.2 vs 67.7, P < .0001). No
      significant improvement between 6 and 18 months after implementation groups (P =
      .16) was noted. Prior to electronic health record implementation, the nurses were
      uncertain yet hopeful about the benefits. However, 18 months after implementing a
      comprehensive electronic health record, challenges remain regarding cumbersome
      documentation processes and promoting interdisciplinary communication. Thus, the
      results demonstrate a gap between preimplementation expectations and the
      postimplementation reality of the actual experience. Nonetheless, some subjects
      have experienced positive benefits after implementation of the comprehensive
      electronic health record and remain hopeful for the future.

PMID- 22584881
TI  - 8-[2-(2-Pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid and its
      diastereomers improve age-related cognitive deterioration.
AB  - Racemic 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA), a
      linoleic acid derivative with cyclopropane rings instead of cis-double bonds,
      contains possible four diastereomers such as alpha,alpha-, alpha,beta-,
      beta,alpha-, and beta,beta-DCP-LA. The present study examined the effect of
      racemic and diastereomeric DCP-LA on age-related learning and memory disorders
      using accelerated-senescence-prone mice 8 (SAMP8) and accelerated-senescence
      resistant mice 1 (SAMR1). In the water maze test, the acquisition and retention
      latencies for SAMP8 mice were significantly longer than the latency for SAMR1
      mice, indicating spatial learning and memory impairment for SAMP8 mice. All the
      racemic (1 mg/kg, per os) and diastereomeric DCP-LA (0.25 mg/kg, per os)
      significantly shortened the acquisition latency for SAMP8 mice, and racemic,
      alpha,alpha- and alpha,beta-DCP-LA significantly shortened the retention latency,
      with the advantage greater than the acetylcholine (ACh) esterase inhibitor
      galanthamine. The results of the present study show that all the racemic and
      diastereomeric DCP-LA, has the potential to improve age-related learning and
      memory deterioration, the potential varying among them.

PMID- 22584882
TI  - Unilateral vitelliform phenotype in autosomal recessive bestrophinopathy.
AB  - AIMS: It was the aim of this study to report on a patient in whom a novel
      mutation in the BEST1 gene was responsible for unilateral vitelliform phenotype
      in autosomal recessive bestrophinopathy (ARB). METHODS: An 8-year-old young girl
      (proband) with unilateral vitelliform phenotype underwent a complete
      ophthalmologic examination at baseline (time of diagnosis) and 2 years later.
      Genomic DNA was extracted to look for BEST1 gene mutations in the patient and her
      parents. RESULTS: Fundus autofluorescence imaging and spectral-domain optical
      coherence tomography showed unchanged findings in the right eye over the 2-year
      follow-up period. Conversely, both fundus autofluorescence imaging and spectral
      domain optical coherence tomography showed a partial reabsorption of the hyper
      autofluorescent/hyper-reflective subretinal material in the left macula over the
      2-year follow-up period. On BEST1 gene analysis, the patient presented a novel
      mutation c.535_537delAAC (p.Asn179del) in homozygous condition; interestingly,
      despite the absence of parents' consanguinity, both the father and mother showed
      the same novel mutation in heterozygous condition. CONCLUSION: This case of
      unilateral vitelliform phenotype further supports the notion that ARB represents
      a disease spectrum in terms of severity, age at onset and heritability.

PMID- 22584883
TI  - Coffee melanoidins: structures, mechanisms of formation and potential health
      impacts.
AB  - During the roasting process, coffee bean components undergo structural changes
      leading to the formation of melanoidins, which are defined as high molecular
      weight nitrogenous and brown-colored compounds. As coffee brew is one of the main
      sources of melanoidins in the human diet, their health implications are of great
      interest. In fact, several biological activities, such as antioxidant,
      antimicrobial, anticariogenic, anti-inflammatory, antihypertensive, and
      antiglycative activities, have been attributed to coffee melanoidins. To
      understand the potential of coffee melanoidin health benefits, it is essential to
      know their chemical structures. The studies undertaken to date dealing with the
      structural characterization of coffee melanoidins have shown that
      polysaccharides, proteins, and chlorogenic acids are involved in coffee
      melanoidin formation. However, exact structures of coffee melanoidins and
      mechanisms involved in their formation are far to be elucidated. This paper
      systematizes the available information and provides a critical overview of the
      knowledge obtained so far about the structure of coffee melanoidins, mechanisms
      of their formation, and their potential health implications.

PMID- 22584884
TI  - The effect of type 2 diabetes risk loci on insulin requirements in type 1
      diabetes.
AB  - OBJECTIVE: To analyze the correlation between insulin requirements of type 1
      diabetic (T1D) patients and genotype at type 2 diabetes (T2D) risk loci, obtained
      in our genome-wide association study. METHODS: From a database of detailed
      insulin dosing of 567 patients, we selected 177 for whom we also had genome-wide
      genotyping data. Using PLINK software, we examined the association between
      insulin requirement as a quantitative trait and nineteen T2D risk loci. RESULTS:
      Out of 19 single-nucleotide polymorphisms (SNPs), rs13266634 on chromosome 8 and
      rs7901695 on chromosome 10 showed nominal significance of association (p < 0.05).
      The first SNP is nonsynonymous (325 Arg>Trp) and maps to the SLC30A8 gene
      encoding the beta-cell-specific ZnT8 zinc transporter, while the second is an
      intronic SNP in TCF7L2, the strongest known T2D association. Both loci exert
      their effect on beta-cells and, in both, the T2D risk allele is associated with
      lower insulin requirements. CONCLUSION: We identified two T2D susceptibility loci
      that modulate insulin requirements in T1D patients. Our results are consistent
      with the association of lower insulin secretion with higher insulin sensitivity.
      To explain the continuation of this correlation after beta-cell destruction, we
      hypothesize an epigenetic mechanism that alters insulin responsiveness in T1D
      patients based on beta-cell function in early life. Such knowledge may allow a
      more precise approach to treatment.

PMID- 22584885
TI  - Association of chronic diseases and impairments with disability in older adults:
      a decade of change?
AB  - BACKGROUND: Little is known about how the relationship between chronic disease,
      impairment, and disability has changed over time among older adults. OBJECTIVE:
      To examine how the associations of chronic disease and impairment with specific
      disability have changed over time. RESEARCH DESIGN: Repeated cross-sectional
      analysis, followed by examining the collated sample using time interaction
      variables, of 3 recent waves of the Health and Retirement Study. SUBJECTS: The
      subjects included 10,390, 10,621 and 10,557 community-dwelling adults aged 65
      years and above in 1998, 2004, and 2008. MEASUREMENTS: : Survey-based history of
      chronic diseases including hypertension, heart disease, heart failure, stroke,
      diabetes, cancer, chronic lung disease, and arthritis; impairments, including
      cognition, vision, and hearing; and disability, including mobility, complex
      activities of daily living (ADL), and self-care ADL. RESULTS: Over time, the
      relationship of chronic diseases and impairments with disability was largely
      unchanged; however, the association between hypertension and complex ADL
      disability weakened from 1998 to 2004 and 2008 [odds ratio (OR) = 1.24; 99%
      confidence interval (CI), 1.06-1.46; OR = 1.07; 99% CI, 0.90-1.27; OR = 1.00; 99%
      CI, 0.83-1.19, respectively], as it did for hypertension and self-care disability
      (OR = 1.32; 99% CI, 1.13-1.54; OR=0.97; 99% CI, 0.82-1.14; OR = 0.99; 99% CI,
      0.83-1.17). The association between diabetes and self-care disability
      strengthened from 1998 to 2004 and 2008 (OR = 1.21; 99% CI, 1.01-1.46; OR = 1.37;
      99% CI, 1.15-1.64; OR = 1.52; 99% CI, 1.29-1.79), as it also did for lung disease
      and self-care disability (OR = 1.64; 99% CI, 1.33-2.03; OR = 1.63; 99% CI, 1.32
      2.01; OR = 2.11; 99% CI, 1.73-2.57). CONCLUSIONS: Although relationships between
      diseases, impairments, and disability were largely unchanged, disability became
      less associated with hypertension and more with diabetes and lung disease.

PMID- 22584887
TI  - A hybrid Centers for Medicaid and Medicare service mortality model in 3
      diagnoses.
AB  - INTRODUCTION: Reliance on administrative data sources and a cohort with
      restricted age range (Medicare 65 y and above) may limit conclusions drawn from
      public reporting of 30-day mortality rates in 3 diagnoses [acute myocardial
      infarction (AMI), congestive heart failure (CHF), pneumonia (PNA)] from Center
      for Medicaid and Medicare Services. METHODS: We categorized patients with
      diagnostic codes for AMI, CHF, and PNA admitted to 138 Veterans Administration
      hospitals (2006-2009) into 2 groups (less than 65 y or ALL), then applied 3
      different models that predicted 30-day mortality [Center for Medicaid and
      Medicare Services administrative (ADM), ADM+laboratory data (PLUS), and clinical
      (CLIN)] to each age/diagnosis group. C statistic (CSTAT) and Hosmer Lemeshow
      Goodness of Fit measured discrimination and calibration. Pearson correlation
      coefficient (r) compared relationship between the hospitals' risk-standardized
      mortality rates (RSMRs) calculated with different models. Hospitals were rated as
      significantly different (SD) when confidence intervals (bootstrapping) omitted
      National RSMR. RESULTS: The >= 65-year models included 57%-67% of all patients
      (78%-82% deaths). The PLUS models improved discrimination and calibration across
      diagnoses and age groups (CSTAT-CHF/65 y and above: 0.67 vs. 0. 773 vs. 0.761;
      ADM/PLUS/CLIN; Hosmer Lemeshow Goodness of Fit significant 4/6 ADM vs. 2/6 PLUS).
      Correlation of RSMR was good between ADM and PLUS (r-AMI 0.859; CHF 0.821; PNA
      0.750), and 65 years and above and ALL (r>0.90). SD ratings changed in 1%-12% of
      hospitals (greatest change in PNA). CONCLUSIONS: Performance measurement systems
      should include laboratory data, which improve model performance. Changes in SD
      ratings suggest caution in using a single metric to label hospital performance.

PMID- 22584886
TI  - Medications prescribed in emergency departments for nontraumatic dental condition
      visits in the United States.
AB  - BACKGROUND: Prior research has documented factors associated with nontraumatic
      dental condition (NTDC) visits to emergency departments (EDs), but little is
      known about the care received by patients in EDs for NTDC visits. OBJECTIVE: We
      examined national trends in prescription of analgesics and antibiotics in EDs for
      NTDC visits in the United States. RESEARCH DESIGN: We analyzed data from the
      National Hospital Ambulatory Medical Care survey from 1997 to 2007. We used a
      multivariable logistic regression model to examine factors associated with
      receiving analgesics and antibiotics for NTDC visits in EDs. RESULTS: Overall 74%
      received at least 1 analgesic, 56% received at least 1 antibiotic, and 13%
      received no medication at all during NTDC visits to EDs. The prescription of
      medications at EDs for NTDC visits steadily increased over time for analgesics
      (odds ratio=1.11/y, P<0.0001) and antibiotics (odds ratio=1.06/y, P<0.0001). In
      the multivariable analysis, self-pay patients had significantly higher adjusted
      odds of receiving antibiotics, whereas those with nondental reasons for visits
      and children (0-4 y) had significantly lower adjusted odds of receiving a
      prescription for antibiotics in EDs for NTDC visits. Children (0-4 y), adults (53
      72 y), and older adults (73 y and older) had lower adjusted odds (P<0.001) of
      receiving analgesics. CONCLUSIONS: Nationally, analgesic and antibiotic
      prescriptions for NTDC visits to EDs have increased substantially over time. Self
      pay patients had significantly higher odds of being prescribed antibiotics.
      Adults over 53 years and especially those 73 years and older had significantly
      lower odds of receiving analgesics in EDs for NTDC visits.

PMID- 22584888
TI  - The effect of comprehensive behavioral health parity on choice of provider.
AB  - BACKGROUND: "Parity" laws remove treatment limitations for mental health and
      substance-abuse services covered by commercial health plans. A number of studies
      of parity implementations have suggested that parity does not lead to large
      increases in utilization or expenditures for behavioral health services. However,
      less is known about how parity might affect changes in patients' choice of
      providers for behavioral health treatment. RESEARCH DESIGN: We compared
      initiation and provider choice among 46,470 Oregonians who were affected by
      Oregon's 2007 parity law. Oregon is the only state to have enacted a parity law
      that places restrictions on how plans manage behavioral health services. This
      approach has been adopted federally in the Paul Wellstone and Pete Domenici
      Mental Health Parity and Addiction Equity Act. In 1 set of analyses, we assess
      initiation and provider choice using a difference-in-difference approach, with a
      matched group of commercially insured Oregonians who were exempt from parity. In
      a second set of analyses, we assess the impact of distance on provider choice.
      RESULTS: Overall, parity in Oregon was associated with a slight increase (0.5% to
      0.8%) in initiations with masters-level specialists, and relatively little
      changes for generalist physicians, psychiatrists, and psychologists. Patients are
      particularly sensitive to distance for nonphysician specialists. CONCLUSIONS: Our
      results suggest that the Paul Wellstone and Pete Domenici Mental Health Parity
      and Addiction Equity Act may lead to a shift in the use of nonphysician
      specialists and away from generalist physicians. The extent to which these
      changes occur is likely to be contingent on the ease and accessibility of
      nonphysician specialists.

PMID- 22584890
TI  - Enhanced recovery after surgery: benefits for the stoma care patient.
AB  - Enhanced recovery can be seen as the use of evidence and research that when used
      for patients undergoing stoma-forming surgery (and other surgery) leads to a
      better recovery (Lassen et al, 2009; Ahmed et al, 2010). Moving patients towards
      adopting an opinion that 'up and mobile' immediately after surgery is the pathway
      to success, and is an essential element in implementing enhanced recovery after
      surgery. It can lead to several clinical benefits, including fewer complications
      (e.g. infection) and a shorter length of time in hospital (Faiz et al, 2008).
      While having a shorter length of stay is positive, it does result in less time
      being available to the ostomate (person with a stoma) to become proficient with
      their stoma care. Changes need to be made to nursing services to encompass this
      new challenge; for example, the use of preoperative training tools. These changes
      can result in satisfied ostomates (Bryan and Dukes, 2010) who have fewer post
      discharge problems with their stoma. This article outlines the concept of
      enhanced recovery after surgery and its benefits for patients with a stoma.

PMID- 22584889
TI  - The role of continuing care in 9-year cost trajectories of patients with intakes
      into an outpatient alcohol and drug treatment program.
AB  - BACKGROUND: The importance of a continuing care approach for substance use
      disorders (SUDs) is increasingly being recognized. Our prior research found that
      a Continuing Care model for SUDs that incorporates 3 components (regular primary
      care, and specialty SUD and psychiatric treatment as needed) is beneficial to
      long-term remission. The study builds on this work to examine the cost
      implications of this model. OBJECTIVES: To examine associations between receiving
      Continuing Care and subsequent health care costs over 9 years among adults
      entering outpatient SUD treatment in a private nonprofit, integrated managed care
      health plan. We also compare the results to a similar analysis of a
      demographically matched control group without SUDs. STUDY DESIGN: Longitudinal
      observational study. MEASURES: Measures collected over 9 years include
      demographic characteristics, self-reported alcohol and drug use and Addiction
      Severity Index, and health care utilization and cost data from health plan
      databases. RESULTS: Within the treatment sample, SUD patients receiving all
      components of Continuing Care had lower costs than those receiving fewer
      components. Compared with the demographically matched non-SUD controls, those not
      receiving Continuing Care had significantly higher inpatient costs (excess cost =
      $65.79/member-month; P < 0.01) over 9 years, whereas no difference was found
      between those receiving Continuing Care and controls. CONCLUSIONS: Although a
      causal link cannot be established between receiving Continuing Care and reduced
      long-term costs in this observational study, the findings reinforce the
      importance of access to health care and development of interventions that
      optimize patients receiving those services and that may reduce costs to health
      systems.

PMID- 22584891
TI  - Nutritional and fluid requirements: high-output stomas.
AB  - Based on the current available evidence, this article explores the nutritional
      management of those with a high-output stoma. The main alterations required to
      the intake of patients with a high-output stoma include the use of an oral
      rehydration solution to ensure optimum absorption of fluid and sodium, and a high
      calorie, high-protein diet, with the aim of optimizing nutritional status. Diet
      advice should be delivered by a dietitian with experience in managing these
      complex patients. Monitoring of electrolytes and micronutrients is essential, and
      long-term follow up from a multidisciplinary nutrition support team is invaluable
      in coordinating this. Patients with high-output stomas can enjoy good quality of
      life and long-term health if their condition is managed effectively by a well
      organized multidisciplinary team.

PMID- 22584892
TI  - High-output stomas: challenges  with a large laparostomy wound.
AB  - This article explores the management of patients with high-output stomas
      fashioned under acute surgical conditions where management may be difficult owing
      to the presence of a large laparostomy wound. Available products that meet the
      technical demands required to manage these patients, achieve optimal wound
      healing, manage high-output stoma and encourage patient independence are
      considered. A number of strategies to meet the physical and nutritional
      requirements of these patients are discussed along with the importance of the
      multidisciplinary team working together to provide holistic care.

PMID- 22584893
TI  - Ongoing clinical audit: proactive, not reactive.

PMID- 22584894
TI  - High-output stoma management following bowel perforation.
AB  - In this article, the author explores the role of the stoma nurse in the
      community, and how this can support recent initiatives such as The Enhanced
      Recovery Programme and the High Impact Actions for Nurses by providing ongoing
      care in the secondary care setting. This can lead to an improvement in quality of
      care and patient outcomes, which is imperative in the current NHS environment
      where anecdotal evidence suggests that the financial goals managers are required
      to meet are leading to constraints on the number of home visits that the stoma
      nurse can carry out (Breckman, 2005). The case study presented within the article
      shows how the stoma nurse worked with the community team to manage a young woman
      following a traumatic bowel perforation experience.

PMID- 22584895
TI  - The use of barrier creams  for patients with a stoma.

PMID- 22584896
TI  - The angiogenesis suppressor gene AKAP12 is under the epigenetic control of HDAC7
      in endothelial cells.
AB  - Histone deacetylases (HDACs) are a family of 18 enzymes that deacetylate lysine
      residues of both histone and nonhistone proteins and to a large extent govern the
      process of angiogenesis. Previous studies have shown that specific inhibition of
      HDAC7 blocks angiogenesis both in vitro and in vivo. However, the underlying
      molecular mechanisms are not fully understood and hence preclude any meaningful
      development of suitable therapeutic modalities. The goal of the present study was
      to further the understanding of HDAC7 epigenetic control of angiogenesis in human
      endothelial cells using the proteomic approach. The underlying problem was
      approached through siRNA-mediated gene-expression silencing of HDAC7 in human
      umbilical vein endothelial cells (HUVECs). To this end, HUVEC proteins were
      extracted and proteomically analyzed. The emphasis was placed on up-regulated
      proteins, as these may represent potential direct epigenetic targets of HDAC7.
      Among several proteins, A-kinase anchor protein 12 (AKAP12) was the most
      reproducibly up-regulated protein following HDAC7 depletion. This overexpression
      of AKAP12 was responsible for the inhibition of migration and tube formation in
      HDAC7-depleted HUVEC. Mechanistically, H3 histones associated with AKAP12
      promoter were acetylated following the removal of HDAC7, leading to an increase
      in its mRNA and protein levels. AKAP12 is responsible for protein kinase C
      mediated phosphorylation of signal transducer and activator of transcription 3
      (STAT3). Phosphorylated STAT3 increasingly binds to the chromatin and AKAP12
      promoter and is necessary for maintaining the elevated levels of AKAP12 following
      HDAC7 knockdown. We demonstrated for the first time that AKAP12
      tumor/angiogenesis suppressor gene is an epigenetic target of HDAC7, whose
      elevated levels lead to a negative regulation of HUVEC migration and inhibit
      formation of tube-like structures.

PMID- 22584898
TI  - Comparative analysis of polyamine metabolism in benign and neoplastic
      keratinocytic proliferations.
AB  - INTRODUCTION: Polyamines (putrescine, spermidine, and spermine) are polycationic
      compounds that play a central role in keratinocytic proliferation,
      differentiation, and regulation. The objective was to elucidate the polyamine
      metabolic changes that occur in various benign and neoplastic skin
      proliferations. METHODS: The study included 58 patients: 31 with the plaque form
      of psoriasis vulgaris and 27 with non-melanoma skin tumors. The levels of
      putrescine, spermidine, and spermine were detected in lesional and non-lesional
      skin samples. RESULTS: Findings were representative (p < 0.05). Psoriatic lesions
      showed a twofold elevation of all polyamines in lesional skin compared to non
      lesional skin. Spermine had the highest concentration, which suggested a leading
      position of propylamine synthesis in psoriatic pathogenesis. Results on the
      polyamine metabolism of basal cell carcinoma represented basic characteristics
      similar to those of psoriasis. Conversely, squamous-cell carcinoma lesions showed
      the highest concentration of putrescine, suggesting a crucial role of spermidine
      spermine acetyltransferase in their pathogenesis. DISCUSSION: Our findings showed
      different polyamine metabolic changes in lesions from benign and neoplastic
      keratinocytic proliferations. Basal-cell carcinoma polyamine metabolism revealed
      a closer relationship to psoriasis than to squamous-cell carcinoma, which might
      explain its long-term benign course and non-metastatic nature.

PMID- 22584899
TI  - Serum lactate is a useful predictor of death in severe sepsis in patients with
      pemphigus vulgaris.
AB  - BACKGROUND: Serum lactate is a useful prognostic marker in severe sepsis; high
      levels of serum lactate in critically ill patients are related to high mortality
      risk; assessing serum lactate levels in patients with pemphigus vulgaris is
      justified. The objective was to determine the role of serum lactate as a
      predictor of shock and its outcome in patients with pemphigus vulgaris and severe
      sepsis without acute organ dysfunction. METHODS: Thirty-seven patients with
      pemphigus vulgaris, 22 with severe sepsis and 15 without sepsis. Blood lactate
      levels were analyzed. The outcome was recorded as survival or non-survival.
      RESULTS: High serum lactate levels, compared with intermediate and low levels,
      were significantly associated with increased 28-day mortality in patients with
      severe sepsis. The 28-day mortality for the cohort was 27.3%. CONCLUSIONS:
      Initial serum lactate was associated with mortality in pemphigus vulgaris with
      severe sepsis. Patients with severe sepsis and with high serum lactate levels (>=
      4 mmol/L) constitute a potential risk group that may benefit from more aggressive
      treatment.

PMID- 22584900
TI  - Comparison of in vitro and in vivo ultraviolet protective properties of PET
      textile samples.
AB  - BACKGROUND: Many studies have been devoted to the problem of harmful effects of
      UV radiation on human skin. The incidence rate for all forms of skin cancer is
      rising quickly. Considering this fact, there is currently a need for diligent
      preventive work, not only from dermatologists but also from other doctors and
      scientists. Textiles represent simple and effective protection against UV
      radiation. Good protective clothing can reduce UV radiation on the surface of
      skin by at least 95%. Even though numerous studies present the effects of various
      textile parameters on UV protection, not many have been conducted for determining
      the degree of agreement between in vivo and in vitro measurements of UPF.
      METHODS: This study presents the effect of various constructional parameters on
      UPF values (determined using spectrophotometry). The phenomenon of minimal
      erythema doses on the skin of test subjects was tested based on in vitro
      calculated UPF values. RESULTS: Despite some differences in values, the study
      nevertheless showed a good correlation between both methods and confirms the
      congruity of in vivo and in vitro UPF values. CONCLUSIONS: It is clear that both
      methods are needed for a more precise look at the UV protection offered by
      textiles.

PMID- 22584901
TI  - Epidemiologic and genetic characteristics of alopecia areata (part 2).
AB  - Alopecia areata (AA) is hypothesized to be an organ-specific autoimmune disease
      mediated by T cells to the hair follicles. Despite the fact that most cases of AA
      are sporadic, there is an accumulation of evidence that AA is a complex
      multigenetic trait with components of inherited predisposition. In the last
      decade, rapid progress in molecular genetics and biotechnology has led to the
      identification of many candidate genes in humans that confer susceptibility to
      AA. The first part of this review focused on the association of HLA genes with
      the disease. The second part reviews non-HLA and other genes associated with AA,
      including the autoimmune regulator (AIRE) gene. Recently, the lymphoid-specific
      protein tyrosine phosphatase, non-receptor type 22 (PTPN22) gene was found to be
      an additional immunoregulatory gene associated with AA. In addition, alleles of
      genes coding for cytokines and their receptors, such as the interleukin-1
      receptor antagonist (IL1RN) and chemokines (MCP-1), have also been associated
      with AA. Some studies have hypothesized that filaggrin gene mutations (FLG) may
      also play a role in AA, particularly in patients with comorbid atopic disease.
      MX1 is another new candidate gene in AA. Thus, this second part of the review
      completes the overview of current knowledge about the molecular genetics of AA
      begun in the first part.

PMID- 22584903
TI  - Atypical fibroxanthoma with dermal amyloid deposit.
AB  - Atypical fibroxanthoma (AFX) has been associated with several secondary changes,
      such as keloidal areas, myxoid or chondroid changes, osteoclast-like giant cells,
      sclerosis, fibrosis, pigmentation, hyalinization, or hemorrhagic areas. We report
      a case of an AFX 4 cm in diameter on the forehead of a 77-year-old male patient.
      There were dermal amyloid deposits intermingled with the tumor fascicles on the
      periphery of the lesion. A moderate inflammatory chronic lymphoplasmacytic
      infiltrate was found in the periphery of the tumor. The amyloid deposits were
      positive with Congo red staining (but negative after permanganate-treatment). The
      deposit was also immunostained with antibodies against CKs (AE1/AE3 and CK5/6).
      It did not stain with anti-amyloid A, or with antibodies against either kappa
      light or lambda light chains. Therefore the amyloid deposit was keratinic in
      nature.

PMID- 22584902
TI  - Bortezomib and bilateral herpes zoster.
AB  - Bortezomib is a proteasome inhibitor that has proven to be a very effective
      treatment for multiple myeloma. There is considerable debate about the potential
      for reactivation of the varicella zoster virus (VZV) in patients with multiple
      myeloma during treatment with bortezomib. This report describes the case of a 70
      year-old patient with multiple myeloma that developed bilateral herpes zoster
      shortly after being treated with bortezomib. Furthermore, it emphasizes the
      importance of using an antiviral prophylaxis with acyclovir in these patients
      treated with bortezomib.

PMID- 22584904
TI  - Fernando Camargo: no limits to learning about stem cells. Interview by Caitlin
      Sedwick.

PMID- 22584905
TI  - Spectraplakins: master orchestrators of cytoskeletal dynamics.
AB  - The dynamics of different cytoskeletal networks are coordinated to bring about
      many fundamental cellular processes, from neuronal pathfinding to cell division.
      Increasing evidence points to the importance of spectraplakins in integrating
      cytoskeletal networks. Spectraplakins are evolutionarily conserved giant
      cytoskeletal cross-linkers, which belong to the spectrin superfamily. Their genes
      consist of multiple promoters and many exons, yielding a vast array of
      differential splice forms with distinct functions. Spectraplakins are also unique
      in their ability to associate with all three elements of the cytoskeleton: F
      actin, microtubules, and intermediate filaments. Recent studies have begun to
      unveil their role in a wide range of processes, from cell migration to tissue
      integrity.

PMID- 22584906
TI  - DRP1-dependent mitochondrial fission initiates follicle cell differentiation
      during Drosophila oogenesis.
AB  - Exit from the cell cycle is essential for cells to initiate a terminal
      differentiation program during development, but what controls this transition is
      incompletely understood. In this paper, we demonstrate a regulatory link between
      mitochondrial fission activity and cell cycle exit in follicle cell layer
      development during Drosophila melanogaster oogenesis. Posterior-localized clonal
      cells in the follicle cell layer of developing ovarioles with down-regulated
      expression of the major mitochondrial fission protein DRP1 had mitochondrial
      elements extensively fused instead of being dispersed. These cells did not exit
      the cell cycle. Instead, they excessively proliferated, failed to activate Notch
      for differentiation, and exhibited downstream developmental defects.
      Reintroduction of mitochondrial fission activity or inhibition of the
      mitochondrial fusion protein Marf-1 in posterior-localized DRP1-null clones
      reversed the block in Notch-dependent differentiation. When DRP1-driven
      mitochondrial fission activity was unopposed by fusion activity in Marf-1
      depleted clones, premature cell differentiation of follicle cells occurred in
      mitotic stages. Thus, DRP1-dependent mitochondrial fission activity is a novel
      regulator of the onset of follicle cell differentiation during Drosophila
      oogenesis.

PMID- 22584907
TI  - Tks5-dependent formation of circumferential podosomes/invadopodia mediates cell
      cell fusion.
AB  - Osteoclasts fuse to form multinucleated cells during osteoclastogenesis. This
      process is mediated by dynamic rearrangement of the plasma membrane and
      cytoskeleton, and it requires numerous factors, many of which have been
      identified. The underlying mechanism remains obscure, however. In this paper, we
      show that Tks5, a master regulator of invadopodia in cancer cells, is crucial for
      osteoclast fusion downstream of phosphoinositide 3-kinase and Src. Expression of
      Tks5 was induced during osteoclastogenesis, and prevention of this induction
      impaired both the formation of circumferential podosomes and osteoclast fusion
      without affecting cell differentiation. Tyrosine phosphorylation of Tks5 was
      attenuated in Src-/- osteoclasts, likely accounting for defects in podosome
      organization and multinucleation in these cells. Circumferential invadopodia
      formation in B16F0 melanoma cells was also accompanied by Tks5 phosphorylation.
      Co-culture of B16F0 cells with osteoclasts in an inflammatory milieu promoted the
      formation of melanoma-osteoclast hybrid cells. Our results thus reveal an
      unexpected link between circumferential podosome/invadopodium formation and cell
      cell fusion in and beyond osteoclasts.

PMID- 22584909
TI  - Lenalidomide in solid tumors.
AB  - BACKGROUND: Lenalidomide is a thalidomide analogue with immunomodulatory and anti
      angiogenic properties that include altering cytokine production, activating T
      cells, and augmenting natural killer cell function. Lenalidomide is approved by
      the U.S. Food and Drug Administration (FDA) for single-agent treatment of
      myelodysplastic syndromes associated with a 5q deletion and as a combination
      therapy with dexamethasone for the treatment of multiple myeloma. METHODS: All
      prospective phase I-III clinical trials and preclinical data published until
      October 2011 and relevant literature were reviewed. RESULTS: In phase I and/or II
      studies of single-agent lenalidomide in patients with advanced cancer, responses
      were reported in patients with prostate, thyroid, hepatocellular, pancreatic, and
      renal cancer and melanoma. The most common toxicities were hematologic, and in
      the first clinical trials, thrombotic events were noted. When anticoagulation
      prophylaxis and exclusion of patients with a history of thrombosis were
      implemented, thrombotic complications became uncommon. CONCLUSION: Monitoring of
      blood counts and for evidence of thromboembolic events is essential for patients
      treated with lenalidomide. Ongoing trials of lenalidomide combination therapy
      offer a treatment option for patients with advanced cancer and will better define
      the role of lenalidomide in solid tumors.

PMID- 22584910
TI  - Genetic study of 12 X-STRs in Malay population living in and around Kuala Lumpur
      using Investigator Argus X-12 kit.
AB  - We investigated 12 X-chromosomal short tandem repeat (STR) polymorphisms in 283
      unrelated Malay individuals (160 males and 123 females) living in and around
      Kuala Lumpur using the Investigator Argus X-12 kit. Heterozygosity among the
      present 12 X-STRs showed a distribution of from 55.3 to 93.5 %. The diversity
      values of the haplotypes constructed using four closely linked groups were all
      higher than 0.9865. A comparison of allelic frequency in each system and
      haplotype variation indicated that the nature of these X-STRs in the Malay
      population differed from that in East Asian, European, or African populations.
      Several microvariant alleles found in the Malay population were characterized and
      compared with known sequence data. The present data may be helpful in forensic
      casework such as personal identification and kinship testing in the Malay
      population in Malaysia.

PMID- 22584911
TI  - Relationship between the extent of labral lesions and the frequency of
      glenohumeral dislocation in shoulder instability.
AB  - PURPOSE: This study aimed to evaluate the relationship between the extent of the
      labral lesion and the frequency of glenohumeral dislocation in patients with
      shoulder instability. METHODS: Ninety-three patients, who underwent surgical
      treatment at our clinic for chronic anterior shoulder dislocation, were selected
      and divided into 3 groups (group I: only Bankart lesion; group II: Bankart and
      SLAP lesions; group III: circumferential-labral lesion). The pre-operative
      frequency of dislocation, intraoperative findings, operation time, post-operative
      clinical score, and range of motion 2 years after surgery were analysed and
      compared among the 3 groups. RESULTS: The time interval from the initial
      dislocation to operation was significantly shorter in group III than in groups I
      and II (P = 0.034 and P = 0.046, respectively). The median number of preoperative
      dislocations was also significantly less in group III than in groups I and II (P
      = 0.025 and P = 0.044, respectively). In all groups, the clinical scores
      (Constant, Rowe, and visual analogue scale) improved significantly post
      operatively, and there were no significant differences in the scores between the
      different groups. All patients returned to work, and most patients returned to
      their preoperative sports activity levels. CONCLUSION: The extent of the labral
      lesion is not always related to the number of dislocations; therefore, treatment
      should not be based on this. LEVEL OF EVIDENCE: Retrospective comparative study,
      Level III.

PMID- 22584913
TI  - New catalysts with unsymmetrical N-heterocyclic carbene ligands.
AB  - The importance of unsymmetrical N-heterocyclic carbenes (uNHCs) as ligands in
      metal-catalyzed reactions is undeniable. While uNHCs show similar properties as
      compared with symmetrical NHCs, dissymmetrization allows for further fine-tuning.
      The introduction of chelatization, hemilability, bifunctionality, shielding
      effects, and chirality-transfer influences the catalyst's stability, reactivity,
      and selectivity, thus offering access to tailor-made systems including mono- and
      multidentate uNHC ligands. Based on selected examples, the structure-reactivity
      relationship of uNHCs employed in metal catalysts is presented. The focus is on
      catalytically active complexes, which either offer access to new applications or
      lead to significantly improved results in metal-catalyzed reactions.

PMID- 22584912
TI  - Evaluation of sterilization methods following contamination of hamstring
      autograft during anterior cruciate ligament reconstruction.
AB  - PURPOSE: Inadvertent contamination of the hamstring autograft during ACL
      reconstruction is infrequent, but can result in significant complications. The
      purpose of this study is to evaluate bacterial contamination of hamstring
      autografts dropped onto the operating room floor and methods of graft
      decontamination. METHODS: Hamstring tendons were harvested from patients. Excess
      tendon not used in the ACL procedure was divided into 6 segments. Segments were
      assigned to 6 groups (A through F, N = 30 in each group): group A: uncontaminated
      graft immediately postharvest (control), group B: graft dropped onto the floor (5
      s), group C: graft dropped onto the floor (15 s). grafts in groups D to F were
      dropped onto floor for 15 s then rinsed with saline (group D), bacitracin
      solution (group E) or chlorhexidine 4 % solution (group F) for 3 min. All grafts
      were sent to the microbiology laboratory for anaerobic and aerobic cultures.
      RESULTS: Cultures were positive in 23 % of graft segments from group A (7/30), 33
      % of grafts from group B (10/30), 23 % from group C (7/30), 30 % from group D
      (9/30) and 3 % from both group E (1/30) and group F (1/30). Sixteen unique
      organisms were identified, with Staphylococcus aureus as the most common isolate.
      Grafts rinsed in either bacitracin solution or 4 % chlorhexidine solutions were
      significantly less likely to be culture positive when compared to control graft
      segments (p < 0.05). However, there was no significant difference between
      uncontaminated grafts retrieved in <5 versus 15 s from the floor. CONCLUSION:
      This study supports the practice of decontaminating a dropped ACL hamstring
      autograft using either 4 % chlorhexidine or bacitracin solution. Specimens should
      be retrieved sterilely and washed for at least 3 min. This study also
      demonstrates no advantage in retrieval time of less than 5 s as compared to 15 s
      for uncontaminated graft. Hamstring harvest in ACL reconstruction may result in
      positive cultures, thus routine soaking of the hamstring autograft in either
      bacitracin or 4 % chlorhexidine solution is recommended. In addition, dropped
      hamstring autograft can be effectively sterilized with bacitracin or 4 %
      chlorhexidine solution. LEVEL OF EVIDENCE: II.

PMID- 22584914
TI  - Trial of Chinese medicine Wu-Ling-San for acute low-tone hearing loss.
AB  - PURPOSE: We used new criteria to elucidate the demographics of acute low-tone
      sensorineural hearing loss (ALHL) and tested the Chinese medicine Wu-Ling-San as
      a treatment for ALHL. PROCEDURES: We reviewed the medical records of patients
      with ALHL seen at the outpatient clinic of the Social Insurance Central General
      Hospital in Tokyo from April 2006 through August 2011. Patients were treated with
      an oral steroid, a diuretic, or Wu-Ling-San; alone or in combination. RESULTS: We
      identified 130 definite and 48 probable ALHL cases. The mean age and male-to
      female ratio in probable cases were significantly higher than those in definite
      cases (p < 0.05). The steroid-Wu-Ling-San combination was significantly more
      effective (100% recovery) than the diuretic alone (59%), Wu-Ling-San alone (62%),
      or the steroid-diuretic combination (60%, p < 0.05). CONCLUSIONS: ALHL can
      develop in older patients more frequently than we expected. The steroid-Wu-Ling
      San combination is a possible new treatment for ALHL.

PMID- 22584915
TI  - A facile route for the fabrication of large-scale gate-all-around nanofluidic
      field-effect transistors with low leakage current.
AB  - Active modulation of ions and molecules via field-effect gating in nanofluidic
      channels is a crucial technology for various promising applications such as DNA
      sequencing, drug delivery, desalination, and energy conversion. Developing a
      rapid and facile fabrication method for ionic field-effect transistors (FET) over
      a large area may offer exciting opportunities for both fundamental research and
      innovative applications. Here, we report a rapid, cost-effective route for the
      fabrication of large-scale nanofluidic field-effect transistors using a simple,
      lithography-free two-step fabrication process that consists of sputtering and
      barrier-type anodization. A robust alumina gate dielectric layer, which is formed
      by anodizing sputtered aluminium, can be rapidly fabricated in the order of
      minutes. When anodizing aluminium, we employ a hemispherical counter electrode in
      order to give a uniform electric field that encompasses the whole sputtered
      aluminium layer which has high surface roughness. In consequence, a well-defined
      thin layer of alumina with perfect step coverage is formed on a highly rough
      aluminium surface. A gate-all-around nanofluidic FET with a leak-free gate
      dielectric exhibits outstanding gating performance despite a large channel size.
      The thin and robust anodized alumina gate dielectric plays a crucial role in
      achieving such excellent capacitive coupling. The combination of a gate-all
      around structure with a leak-free gate dielectric over a large area could yield
      breakthroughs in areas ranging from biotechnology to energy and environmental
      applications.

PMID- 22584917
TI  - Expert's comment concerning grand rounds case entitled "Cervical spine injury in
      the young child" (Navin Nashiel Ramrattan, F. Cumhur Oner, Bronek M. Boszczyk,
      Rene M. Castelein, Paul F. Heini).

PMID- 22584918
TI  - Natural history of Pott's kyphosis.
AB  - The natural history of Pott's kyphosis is different from that of other spinal
      deformities. After healing of the spinal infection, the post-tubercular kyphosis
      in adults is static but in children variable progression of the kyphosis is seen.
      The changes occurring in the spine of children, after the healing of the
      tubercular lesion, are more significant than the changes that occur during the
      active stage of infection. During growth, there is a decrease in deformity in 44
      % of the children, an increase in deformity in 39 % of the children and no change
      in deformity in 17 % of the children. The critical factor leading to the progress
      of the deformity is dislocation of the facets. This can be identified on
      radiographs by the "Spine-at-risk" signs. Dislocation of facets at more than two
      levels can lead to the "Buckling collapse" of the spine, which is
      characteristically seen only in severe tubercular kyphosis in children. Age below
      10 years, vertebral body loss of more than 1-1.5 pre-treatment deformity angle of
      greater than 30 degrees  and involvement of cervicothoracic or thoracolumbar
      junction are the other risk factors for deformity progression. In children, the
      kyphosis can progress even after healing of the spinal infection and hence
      children with spinal tuberculosis must be followed-up till skeletal maturity. 

PMID- 22584919
TI  - Ajust single incision transobturator sling procedure for stress urinary
      incontinence: results after 1-year follow-up.
AB  - INTRODUCTION AND HYPOTHESIS: Data on the Ajust, a new single-incision sling
      procedure for female stress urinary incontinence (SUI) management, remain scarce
      and limited to a 1-year follow-up. Our goal was to assess the efficacy of this
      procedure after a 1-year follow-up. METHODS: This prospective evaluation involved
      95 consecutive patients implanted with Ajust at a single centre. All patients had
      SUI on urodynamics due to urethral hypermobility, 33 % had preoperative
      overactive bladder (OAB) symptoms and none had detrusor overactivity. Ninety-two
      patients were treated on an outpatient basis, and 3 patients had general
      anaesthesia. Postoperative assessment was conducted at 1, 6, 12 months, and
      yearly thereafter. The main outcome measure was pad usage. Secondary parameters
      were self-reported SUI episodes, OAB symptoms, data of clinical examination,
      satisfaction using the Patient Global Impression of Improvement (PGI-I) scale,
      postoperative pain, and adverse events. RESULTS: After a mean follow-up of 21 +/-
      6 months (12-32), 76 out of 95 patients used no pads or one dry security pad,
      showing a success rate of 80 %. Seventy-nine out of 95 patients had no more SUI
      related leakage. Only 6 patients experienced late recurrence of SUI after 6
      months' follow-up. Perioperative complications included 1 case of vaginal
      hematoma, 1 case of acute urinary retention, 2 cases of urinary tract infection,
      all managed conservatively. Half of the patients had no pain after day 1, free of
      medications. Late complications were vaginal erosion in 1 case, and pain during
      exertion in 2 cases. CONCLUSIONS: The Ajust single incision transobturator sling
      is a safe and effective procedure, with durable results after 1 year.

PMID- 22584920
TI  - Maximum urethral closure pressure in women: normative data and evaluation as a
      diagnostic test.
AB  - INTRODUCTION AND HYPOTHESIS: Our goal was to identify correlates of maximum
      urethral closure pressure (MUCP) and MUCP as a diagnostic test for stress urinary
      incontinence (SUI). METHODS: This study was a retrospective review of women with
      non-neurological referrals for urinary incontinence between1995 and 2006.
      RESULTS: We studied the characteristics of 8,644 women who underwent urodynamics
      for non-neurological referrals. Mean MUCP was 48 cm H(2)O in urodynamic stress
      incontinence (USI), 50 cm H(2)O in mixed urinary incontinence (MUI), 65 cm H(2)O
      in detrusor overactivity incontinence (DOI) and 67 cm H(2)O for continent women .
      Age and MUCP were negatively correlated in all groups. Multiple regression
      analysis showed lower levels of MUCP in women with USI who also had previous
      hysterectomy or anti-incontinence surgery or who were in an older age group.
      Previous anti-incontinence surgery and older age were risk factors for lower MUCP
      in women with MUI and DOI. Receiver operator curves did not show MUCP to have
      utility as a diagnostic test despite age and parity stratification. MUCP < 20 cm
      H(2)O showed a sensitivity of 5 % and specificity of 98 % in diagnosing USI.
      CONCLUSIONS: MUCP failed to meet the criteria for a diagnostic test. Women with
      USI and MUI have lower MUCP than women with DOI and continent women in each
      decade of life. MUCP decreases with age.

PMID- 22584921
TI  - Diabetes mellitus and female urinary incontinence: a time for change.

PMID- 22584922
TI  - The effect of pregnancy on hiatal dimensions and urethral mobility: an
      observational study.
AB  - INTRODUCTION AND HYPOTHESIS: Childbirth is an established risk factor of pelvic
      floor dysfunction. The role of pregnancy is, however, not fully understood. This
      study was designed to evaluate the potential effect of pregnancy on pelvic floor
      function. The hypothesis was: Pregnancy has no effect on urethral mobility and
      levator hiatal dimensions. METHODS: This was a reanalysis of the translabial
      3D/4D ultrasound volume data of 688 nulliparous pregnant women seen in the late
      3rd trimester and again 4 months postpartum and that of 74 nulliparous,
      nonpregnant volunteers in previously reported studies. Hiatal dimensions and
      urethral mobility were determined as the outcome parameters. Multivariate
      regression analysis was performed after adjusting for age and BMI between the
      pregnant and nonpregnant cohorts. RESULTS: Comparison of 3rd trimester data of
      the pregnant cohort with that of the nonpregnant nulliparae revealed a 27 % and
      41 % increase in hiatal area at rest and on Valsalva and an increase in segmental
      urethral mobility by 64 % to 91 % in late pregnancy. About 70 % of this
      difference in hiatal dimensions, but virtually identical differences in urethral
      mobility, were observed when comparing nonpregnant controls with women 4 months
      after prelabour or 1st stage caesarean section. CONCLUSION: Both hiatal
      dimensions and urethral mobility were markedly higher in women in late pregnancy
      and at 4 months after prelabour/1st stage caesarean section compared to
      nulliparous controls. The hormonal and mechanical changes of pregnancy may have
      an irreversible effect on the pelvic floor.

PMID- 22584923
TI  - The effect of concealed concomitant anal incontinence symptoms in patients with
      urinary incontinence on their quality of life.
AB  - INTRODUCTION AND HYPOTHESIS: We evaluated the bother of concomitant anal
      incontinence (AI) in women with urinary incontinence (UI) who do not primarily
      report their anal symptoms. METHODS: This prospective study assessed patients
      with complaings of primary UI without initially reporting anal symptoms. After
      urogynecological assessment, all patients were asked to complete the validated
      versions of the Urogenital Distress Inventory (UDI-6), Incontinence Impact
      Questionnaire (IIQ-7), Pelvic Floor and Incontinence Sexual Impact Questionnaire
      (PISQ-12), Wexner Incontinence Scale (WIS) score, and Beck Anxiety Inventory
      (BAI). Patients who scored nil in the WIS constituted the group of only UI, and
      patients with scores >=1 were grouped as double incontinence (DI)., and the
      groups were compared. RESULTS: Among 136 women, 69.1 % (94) had only UI, whereas
      30.9 % (42) had DI. There were no differences in age, parity, body mass index
      (BMI), and prolapse status between patients with UI and those with DI, except
      menopausal status. Women with DI scored worse for IIQ-7, PISQ-12, and BAI
      questionnaires compared with women with UI. This difference was not statistically
      significant for IIQ-7 only. CONCLUSIONS: Our data show that concealed AI symptoms
      may contribute to the anxiety of the patient and even alter the perception of
      urinary symptoms. Actually, a significant number of women suffer from DI without
      reporting their anal symptoms, which results in underdiagnosing of concomitant
      AI. To prevent the suboptimal management of patients with lower urinary tract
      symptoms, standardized questionnaires for AI should be included in the evaluation
      of all patients with lower urinary tract symptoms.

PMID- 22584924
TI  - Efficacy of TVT-SECUR and factors affecting cure of female stress urinary
      incontinence: 3-year follow-up.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study was to evaluate the efficacy
      of the TVT-SECUR procedure for treating stress urinary incontinence (SUI) and to
      identify factors affecting cure during 3 years of follow-up. METHODS: We
      prospectively followed patients until 1 year postoperatively and contacted them
      to revisit the clinic at 3 years. Ninety-six women who underwent TVT-SECUR (H
      type: 42, U type: 54) were followed up for at least 3 years. Patients were
      evaluated using the Severity Index for Urinary Incontinence, the Incontinence
      Quality of Life questionnaire, and the Bristol Female Lower Urinary Tract Symptom
      Short Form questionnaire at baseline and at each postoperative visit. Patient
      satisfaction and complications were evaluated. Surgical outcome was assessed
      according to the Severity Index for Urinary Incontinence. Multivariate regression
      analysis was used to identify preoperative factors independently associated with
      cure. RESULTS: The 3-year success rate was 91.7 % (cure 72.9 %, improved 18.8 %).
      The success rate was maintained from 94.8 % at 1 year to 91.7 % at 3 years, but
      the cure rate decreased significantly from 85.4 % at 1 year to 72.9 % at 3 years.
      Patient satisfaction rate was 85.4 %. Cure rates were lower in patients with
      Valsalva leak point pressure (VLPP) <60 cmH(2)O (79.5 % vs. 52.2 %, p = 0.010).
      Multivariate analysis showed that only low VLPP was associated with a lower cure
      rate. CONCLUSIONS: The cure rate of female SUI after the TVT-SECUR procedure was
      not sustained, but the overall success rate was maintained over time. Low VLPP
      predicted failure to sustain cure.

PMID- 22584925
TI  - On the relevance of uniaxial tensile testing of urogynecological prostheses: the
      effect of displacement rate.
AB  - INTRODUCTION AND HYPOTHESIS: Uniaxial tensile testing is commonly used to
      calculate values of mechanical properties of urogynecological prostheses used in
      stress urinary incontinence and pelvic organ prolapse surgery in women. Clinical
      behavior of these products has been linked to their mechanical properties, hence
      influencing the clinician's preference for one brand or another. The objective of
      this study is to assess the effect of displacement rate used in uniaxial tensile
      testing on peak load, extension at peak load, and initial stiffness of Prolene(r)
      mesh, used as a proxy for urogynecological prostheses. METHODS: Strips of
      Prolene(r) mesh measuring 10 * 30 mm were submitted to uniaxial tensile testing
      at the following rates: 1, 10, 50, 100, and 500 mm/min. Peak load, elongation at
      peak load, and initial stiffness were computed from load vs displacement curves
      at all displacement rates. The effect of displacement rate on these parameters
      was estimated by fitting linear trend lines through the data. RESULTS: The
      displacement rate at which uniaxial tensile testing is performed has significant
      effects on the values of extension at peak load and initial stiffness, but not on
      the peak load. CONCLUSIONS: When urogynecological prostheses are submitted to
      uniaxial tensile testing, studies at more than one displacement rate should be
      performed. More importantly, these displacement rates should be within the range
      of applicability.

PMID- 22584916
TI  - Adherence to antiretroviral therapy and acceptability of planned treatment
      interruptions in HIV-infected children.
AB  - There have been no paediatric randomised trials describing the effect of planned
      treatment interruptions (PTIs) of antiretroviral therapy (ART) on adherence, or
      evaluating acceptability of such a strategy. In PENTA 11, HIV-infected children
      were randomised to CD4-guided PTIs (n = 53) or continuous therapy (CT, n = 56).
      Carers, and children if appropriate, completed questionnaires on adherence to ART
      and acceptability of PTIs. There was no difference in reported adherence on ART
      between CT and PTI groups; non-adherence (reporting missed doses over the last 3
      days or marking <100 % adherence since the last clinical visit on a visual
      analogue scale) was 18 % (20/111) and 14 % (12/83) on carer questionnaires in the
      CT and PTI groups respectively (odds ratios, OR (95 % CI) = 1.04 (0.20, 5.41),
      chi(2) (1) = 0.003, p = 0.96). Carers in Europe/USA reported non-adherence more
      often (31/121, 26 %) than in Thailand (1/73, 1 %; OR (95 % CI) = 54.65 (3.68,
      810.55), chi(2) (1) = 8.45, p = 0.004). The majority of families indicated they
      were happy to have further PTIs (carer: 23/36, 64 %; children: 8/13, 62 %),
      however many reported more clinic visits during PTI were a problem (carer: 15/36,
      42 %; children: 6/12, 50 %).

PMID- 22584926
TI  - Blowing the whistle on the Health and Social Care Bill.

PMID- 22584927
TI  - Writing exclusively for BJN, Lansley dismisses Bill critics.

PMID- 22584928
TI  - Rheumatoid arthritis: role of the nurse and multidisciplinary team.
AB  - Rheumatoid arthritis is a complex chronic inflammatory condition which has both
      musculoskeletal and extra-articular effects. It is the most common inflammatory
      arthropathy, and has the potential to cause a significant impact on quality of
      life. The predominant features of the disease are inflammation, pain, reduced
      levels of function and increased morbidity. Despite the number of treatments
      available to suppress the effects of rheumatoid arthritis, it is not always
      possible to establish good control of the disease. It is imperative that the
      multidisciplinary team are involved with care to ensure that independence is
      maintained and function optimized. The role of the nurse in the management of
      rheumatoid arthritis is varied, ranging from providing specialist advice about
      how to manage the condition to caring for patients who are having joint
      replacements as a result of the increased levels of pain and damage it can cause.

PMID- 22584929
TI  - Musculoskeletal US: examining the joints.
AB  - Musculoskeletal ultrasound (US) is an excellent tool to diagnose muscle, tendon
      and ligament injuries, cystic structures and peripheral nerve compression, as
      well as soft tissue masses, without the risk of ionizing radiation.
      Musculoskeletal US is now routinely used by a growing number of rheumatology and
      sports medicine centres throughout UK. In standard clinical practice, US has an
      extremely useful application in differentiating fluid from soft tissue and
      identifying the severity of joint inflammation. The work described in this
      article was carried out to assess patients' feedback regarding the use of US
      guidance for intra-articular injections and/or the removal of fluid from their
      inflamed knee joints in a nurse-led clinic. Nineteen patients who had US-guided
      knee joint injection/aspiration in the clinic were asked to complete a
      questionnaire regarding their satisfaction with the procedure, and to rate their
      joint pain and patient global assessment (using numerical visual analogue scale)
      before the US-guided procedure, and 1 month after. Results revealed a significant
      improvement (p<0.001) of the joint injection outcome measures and the patients'
      satisfaction of the US-guided procedure. Therefore, musculoskeletal US can
      improve two fundamental clinical skills: the clinical diagnosis of joint
      inflammation, and the accuracy of joint injection/aspiration. This study supports
      the concept that incorporating musculoskeletal US into clinical practice leads to
      significant improvements in patient care. It also reveals that US-guided
      procedures are appreciated by patients.

PMID- 22584930
TI  - Intellectual disability nursing assessment: student reflections.
AB  - Nursing students, Paula and Lynda, reflect on their first academic assessment of
      their 4-year intellectual disability nursing course. The reflection is conducted
      by the second and third authors of this article, and is guided by Gibbs' (1998)
      cycle, highlighting the positive and negative aspects of their 'workbook'
      assignment during their first academic semester. Overall, the use of the workbook
      as an assessment method enabled the students to discover the importance of time
      management, attendance at lectures, database searching, referencing and academic
      writing. The assignment enabled the students to be more prepared for clinical
      practice placement, and develop a basis for future learning and knowledge of
      intellectual disability.

PMID- 22584931
TI  - Coronary artery bypass grafting: quality of life of patients in Karachi.
AB  - In the Third World, cardiac patients often suffer not only from the nature of
      their illnesses, but also the insufficiency of the facilities available. Although
      the effectiveness of coronary artery bypass grafting (CABG) is being evaluated in
      terms of mortality, complications or recurrence of symptoms, empirical studies
      assessing the change in patients' quality of life (QOL) after CABG within the
      Pakistani cultural context are lacking. AIMS: The aims of the present study are
      to assess and compare the change in health-related quality of life before and 1
      month after CABG and to assess the differences in QOL with respect to age, gender
      and cardiac rehabilitation programme attendance. METHOD: A prospective single
      group pre- and post-study design was used, whereby patients completed a
      questionnaire before and 1 month after surgery. Questions considered the person's
      physical capacity, psychological wellbeing, social relationships and satisfaction
      from their health condition. RESULTS: The results indicated a significant
      improvement in patients' physical and psychological health, satisfaction with
      social relationships and overall health status. Younger patients showed
      significantly lower scores on the social domain (reflecting greater
      dissatisfaction with their sex life and personal relationships). Female
      participants showed significantly lower scores in psychological health post
      surgery. Lastly, participants of the cardiac rehabilitation programme scored
      significantly higher in psychological health compared with non-participants.
      CONCLUSION: QOL improved from prior to and 1 month after CABG while differing (in
      specific domains) with respect to age, gender and cardiac rehabilitation
      programme attendance. The findings can be used to develop interventions to
      improve health and QOL in specific domains with respect to specific groups.

PMID- 22584932
TI  - Applying research to practice: exploring the barriers.
AB  - Nurses are not averse to applying research findings to their clinical practice;
      however, there appears to be a number of barriers to achieving this. Generally,
      barriers include lack of time and the need to provide more education surrounding
      the use of research. While these are both valid points, the authors suggest that
      perhaps the solution to the problem is looking at how research is 'sold' to
      practitioners. For example, the use of jargon in research is off-putting to many
      practitioners, which creates an impression that research is associated with
      academia, rather than a tool for practitioners. Also, there may be an unrealistic
      expectation of what 'using research' might mean. Research is seen as the pinnacle
      of evidence, and not a part of evidence-based practice. In this article, the
      authors propose that teaching and expectations of research should focus on the
      application of research to practice. Reviewing and critiquing of research should
      serve the purpose of helping to make decisions about its practical applications,
      rather than for academic use.

PMID- 22584933
TI  - How to use reflection  as a learning tool.

PMID- 22584934
TI  - Pneumonia part 3: management  and prevention of influenza virus.
AB  - This is the third and final article in a series looking at the morbidity and
      mortality associated with community-acquired pneumonia (CAP). It will discuss the
      epidemiology of influenza and the part that it plays in this important disease,
      and will also look at preventive strategies.

PMID- 22584935
TI  - Professional development:  from staff nurse to nurse consultant.  Part 7:
      polishing your portfolio.

PMID- 22584936
TI  - Improving quality of care  for older people.

PMID- 22584937
TI  - Maintaining nursing mentor skills  in a climate of skill-mix austerity.

PMID- 22584939
TI  - Device therapy: Clinical sequelae of cardiac device-related endocarditis.

PMID- 22584938
TI  - The ageing population: is it time for an international convention of rights?
AB  - An increasing ageing population gives rise to many challenges for healthcare
      delivery. The need to ensure that there is respect for the rights and the dignity
      of older patients has been a consistent theme over the last decade. However, the
      vulnerability of this group of patients was highlighted again recently in a
      highly critical Health Service Commissioners Report. This article explores the
      case for a more overt form of rights protection and whether there is a case for a
      Human Rights Convention for the Older Person.

PMID- 22584940
TI  - Acute coronary syndromes: a BRIDGE-ACS over troubled water.

PMID- 22584942
TI  - Risk factors: Is measurement of change in cIMT useful?

PMID- 22584943
TI  - Cardiac resuscitation: Epinephrine to treat cardiac arrest--a double-edged sword.

PMID- 22584941
TI  - Anticoagulation during pregnancy in patients with a prosthetic heart valve.
AB  - Effective anticoagulation is mandatory for pregnant women with mechanical heart
      valves. Oral anticoagulants offer the best maternal protection against
      thrombosis, but their use might be associated with an appreciable risk of fetal
      malformations and pregnancy loss. By contrast, heparin derivatives are associated
      with a reduced risk of fetal damage, but an increased risk of valve thrombosis in
      the mother, even with appropriate dose adjustment and monitoring of therapeutic
      efficacy. Given the varying risks of available anticoagulation strategies, and
      the paucity of data to inform the optimal approach, no single accepted treatment
      option exists for pregnant women with mechanical prosthetic valves. Although low
      molecular-weight heparin is considered more efficacious than unfractionated
      heparin, treatment failures, even at therapeutic levels of factor Xa inhibition,
      have been reported. The risk of warfarin-related embryopathy might be overstated,
      particularly at doses <= 5 mg daily. We advocate an individualized
      anticoagulation strategy that takes into account the patient's preferences, calls
      for the use of vitamin K antagonists throughout pregnancy (substituted with a
      heparin derivative only close to term) for those patients at the greatest risk of
      thromboembolism, and relies on close multidisciplinary collaboration between the
      cardiac and obstetric care teams.

PMID- 22584944
TI  - Severe cerebral vasculitis in systemic lupus erythematosus: from stroke to
      multiple fusiform aneurysms.

PMID- 22584945
TI  - Surface-engineered nanoliposomes by chelating ligands for modulating the
      neurotoxicity associated with beta-amyloid aggregates of Alzheimer's disease.
AB  - PURPOSE: To develop chelating ligand-bound nanoliposomes (NLPs) for the
      prevention and reversal of beta-Amyloid (Abeta) aggregation associated with
      promoting neurotoxicity in Alzheimer disease (AD). METHODS: Four different
      chelating ligands (CuAc, EDTA, histidine and ZnAc) were surface-engineered onto
      NLPs using either covalent or non-covalent conjugation. Successful conjugation of
      chelating ligands onto the surface of NLPs was confirmed by characterization
      studies: SEM, TEM and FTIR analysis. Chelation energetics of EDTA with
      Cu(II)/Zn(II)-Abeta(10-21) and nanoformation of emulsified polymers were computed
      and corroborated with experimental and analytical data using chemometric
      molecular modeling. RESULTS: The modified NLPs produced were spherical in shape,
      127-178 nm in size, with polydispersity index from 0.217-0.920 and zeta potential
      range of -9.59 to -37.3 mV. Conjugation efficiencies were 30-76 %, which
      confirmed that chelating ligands were attached to the NLP surface. CONCLUSIONS:
      In vitro and ex vivo results elucidated the effectiveness of chelating ligand
      bound NLPs for prevention of CuAbeta(1-42) or ZnAbeta(1-42) aggregate buildup
      associated with neurotoxicity in PC12 neuronal cells, as well as promotion of
      intracellular uptake in the presence of Cu(II) or Zn(II) metal ions.

PMID- 22584946
TI  - Characterization of medicinal compounds confined in porous media by neutron
      vibrational spectroscopy and first-principles calculations: a case study with
      ibuprofen.
AB  - PURPOSE: Amorphous formulations of ibuprofen were prepared by confining the drug
      molecules into the porous scaffolds. The molecular interactions between ibuprofen
      and porous media were investigated using neutron vibrational spectroscopy.
      METHODS: Ibuprofen was introduced into the pores using sublimation and adsorption
      method. Neutron vibrational spectra of both neat and confined ibuprofen were
      measured, and compared to the simulated ibuprofen spectra using first-principles
      phonon calculations. RESULTS: The neutron vibrational spectra showed marked
      difference between the neat crystalline and the confined ibuprofen in low
      frequency region, indicating a loss of the overall structural order once the
      ibuprofen molecules were in the pores. Furthermore, the formation of ibuprofen
      dimers, which is found in the crystal structure, was greatly inhibited, possibly
      due to the preferential interactions between the carboxylic acid group of
      ibuprofen (-COOH) and the surface hydroxyl groups of porous scaffolds (Si-OH).
      CONCLUSIONS: The experimental evidence suggests that, at the current drug
      loading, most, if not all, of the confined ibuprofen molecules were bound to the
      pore surfaces via hydrogen bonding. The structural arrangement of ibuprofen in
      the pores appears to be monolayer coverage. In addition, neutron vibrational
      spectroscopy is proven an exceedingly useful technique to study adsorbent
      adsorbate interactions.

PMID- 22584947
TI  - Studies on the effect of the size of polycaprolactone microspheres for the
      dispersion of salbutamol sulfate from dry powder inhaler formulations.
AB  - PURPOSE: To study the effect of the size of the surface-coated polycaprolactone
      (PCL) microparticle carriers on the aerosolization and dispersion of Salbutamol
      Sulfate (SS) from Dry Powder Inhaler (DPI) formulations. METHODS: The
      microparticles were fabricated using an emulsion technique in four different
      sizes (25, 48, 104 and 150 MUm) and later coated with Magnesium stearate (MgSt)
      and leucine. They were characterized by laser diffraction and SEM. The Fine
      Particle Fraction (FPF) of SS from powder mixtures was determined by a Twin Stage
      Impinger (TSI). RESULTS: As the carrier size increased from 25 MUm to 150 MUm,
      the FPF of the SS delivered by the coated PCL particles increased approximately
      four fold. A linear relationship was found between the FPF and Volume mean
      Diameter (VMD) of the particles over this range. CONCLUSIONS: The dispersion
      behaviour of SS from PCL carriers was dependent on the inherent size of the
      carriers and the increased FPF of SS with increased carrier size probably
      reflects the higher mechanical forces produced due to the carrier-carrier
      collisions or collisions between the carrier particles and the internal walls of
      the inhaler during aerosolization.

PMID- 22584948
TI  - Acquired resistance to peloruside A and laulimalide is associated with
      downregulation of vimentin in human ovarian carcinoma cells.
AB  - PURPOSE: Acquired beta-tubulin alterations in human ovarian carcinoma 1A9 cells
      were previously shown to confer resistance to the microtubule stabilizing agents
      peloruside A (PLA) and laulimalide (LAU). We examined the proteome of resistant
      cells to see what other protein changes occurred as a result of the acquired drug
      resistance. METHODS: Two-dimensional differential in-gel electrophoresis was
      performed to explore differentially expressed proteins in the resistant 1A9-R1
      (R1) and 1A9-L4 (L4) cells. The proteins on the gels were identified by MALDI-TOF
      MS, and altered protein abundance was confirmed by Western blotting and
      immunocytochemistry. Vimentin expression was restored in vimentin-deficient L4
      cells by transfecting a full-length human vimentin cDNA, and sensitivity to PLA
      and LAU were tested using an MTT cell proliferation assay. RESULTS: Proteomic
      analysis identified several proteins that were significantly altered in the
      resistant cells relative to the parental 1A9 cells. Using Western blotting and
      immunocytochemistry, a decreased vimentin abundance in the L4 cells was
      validated. Vimentin levels were unchanged in PLA-resistant R1 cells and
      paclitaxel/epothilone-resistant derivatives of 1A9 cells. Vimentin cDNA
      transfection into L4 cells partially restored PLA and LAU sensitivity.
      CONCLUSIONS: Downregulation of vimentin contributes to the resistance of 1A9
      cells to the microtubule stabilizing agents, PLA and LAU.

PMID- 22584949
TI  - Magnetised thermo responsive lipid vehicles for targeted and controlled lung drug
      delivery.
AB  - PURPOSE: Conditions such as lung cancer currently lack non-invasively targetable
      and controlled release topical inhalational therapies. Superparamagnetic iron
      oxide nanoparticles (SPIONs) have shown promising results as a targetable
      therapy. We aimed to fabricate and test the in-vitro performance of particles
      with SPION and drug within a lipid matrix as a potentially targetable and thermo
      sensitive inhalable drug-delivery system. METHODS: Budesonide and SPIONs were
      incorporated into lipid particles using oil-in-water emulsification. Particles
      size, chemical composition, responsiveness to magnetic field, thermosensitiveness
      and inhalation performance in-vitro were investigated. RESULTS: Particles of
      average diameter 2-4 MUm with budesonide and SPIONs inside the lipid matrix
      responded to a magnetic field with 100% extraction at a distance of 5 mm.
      Formulations were shown to have accelerated rate of drug release at hyperthermic
      temperatures (45 degrees C)--controlled release. The produced inhalation dry
      powder presented promising inhalation performance, with an inhalable fine
      particle fraction of 30%. CONCLUSIONS: The lipid system presented thermo
      sensitive characteristics, suitable for controlled delivery, the model drug and
      SPION loaded lipid system was magnetically active and movable using simple
      permanent magnets, and the system demonstrates promise as an effective drug
      vehicle in targeted and controlled inhalation therapy.

PMID- 22584950
TI  - C19orf12 mutations in neurodegeneration with brain iron accumulation mimicking
      juvenile amyotrophic lateral sclerosis.
AB  - Mutations in C19orf12 have been recently identified as the molecular genetic
      cause of a subtype of neurodegeneration with brain iron accumulation (NBIA).
      Given the mitochondrial localization of the gene product the new NBIA subtype was
      designated mitochondrial membrane protein-associated neurodegeneration. Frequent
      features in the patients described so far included extrapyramidal signs and
      pyramidal tract involvement. Here, we report three C19orf12-mutant patients from
      two families presenting with predominant upper and lower motor neuron dysfunction
      mimicking amyotrophic lateral sclerosis with juvenile onset. While extrapyramidal
      signs were absent, all patients showed neuropsychological abnormalities with
      disinhibited or impulsive behavior. Optic atrophy was present in the simplex
      case. T2-weighted cranial MRI showed hypointensities suggestive of iron
      accumulation in the globi pallidi and the midbrain in all patients. Sequence
      analysis of C19orf12 revealed a novel mutation, p.Gly66del, compound heterozygous
      with known mutations in all patients. These patients highlight that C19orf12
      defects should be considered as a differential diagnosis in patients with
      juvenile onset motor neuron diseases. Patients have to be examined carefully for
      neuropsychological abnormalities, optic neuropathy, and signs of brain iron
      accumulation in MRI.

PMID- 22584951
TI  - Fear of heights in ancient China.

PMID- 22584952
TI  - Comparison of chocolate to cacao-free white chocolate in Parkinson's disease: a
      single-dose, investigator-blinded, placebo-controlled, crossover trial.
AB  - A previous questionnaire study suggests an increased chocolate consumption in
      Parkinson's disease (PD). The cacao ingredient contains caffeine analogues and
      biogenic amines, such as beta-phenylethylamine, with assumed antiparkinsonian
      effects. We thus tested the effects of 200 g of chocolate containing 80 % of
      cacao on UPDRS motor score after 1 and 3 h in 26 subjects with moderate non
      fluctuating PD in a mono-center, single-dose, investigator-blinded crossover
      study using cacao-free white chocolate as placebo comparator. At 1 h after
      chocolate intake, mean UPDRS motor scores were mildly decreased compared to
      baseline in both treatments with significant results only for dark chocolate [
      1.3 (95 % CI 0.18-2.52, RMANOVA F = 4.783, p = 0.013  Bonferroni p = 0.021 for 1
      h values)]. A 2 * 2-cross-over analysis revealed no significant differences
      between both treatments [-0.54 +/- 0.47 (95 % CI -1.50 to 0.42), p = 0.258].
      Similar results were obtained at 3 h after intake. beta-phenylethylamine blood
      levels were unaltered. Together, chocolate did not show significant improvement
      over white cacao-free chocolate in PD motor function.

PMID- 22584953
TI  - Inpatient treatment of functional motor symptoms: a long-term follow-up study.
AB  - Functional neurological disorders are common, disabling and often difficult to
      treat. There is little consensus on the best approach to management.
      Multidisciplinary inpatient approaches are employed in some centres for patients
      with severe refractory symptoms, but their efficacy and, in particular, long-term
      outcomes are uncertain. We conducted a study using questionnaires completed
      retrospectively by patients treated at a specialised multidisciplinary inpatient
      programme at the National Hospital for Neurology and Neurosurgery. Consecutive
      patients with functional motor symptoms admitted to this centre between 2006 and
      2008 were invited to participate. Questionnaires were sent at least 2 years after
      discharge. We contacted 32 patients, and 26 responded. The majority had symptoms
      for at least 3 years prior to admission; 58 % of patients reported benefit from
      the programme on discharge. This self-reported benefit to symptoms and function
      was after a 2-year follow-up period in the majority of patients, but return to
      work or cessation of health-related financial benefits was uncommon even in those
      who improved. Seventy-four percent of those questioned stated they would
      recommend the programme to others with similar symptoms. Attribution of symptoms
      to stress or emotional state was correlated with favourable outcome. Our data
      suggest that multidisciplinary inpatient treatment for patients with refractory
      functional motor symptoms provides self-reported benefit in the long-term.
      Prospective analysis of such interventions and the determinants of benefit need
      assessment in order to improve the service and target treatment to patients most
      likely to benefit.

PMID- 22584954
TI  - Multiple cerebral infarctions related to famotidine-induced eosinophilia.

PMID- 22584955
TI  - Codon 200 mutation of the prion gene: genotype-phenotype correlations.
AB  - Genetic mutations as a cause of prion diseases are rare. We describe a large
      family with multiple affected members with the codon E200K prion mutation. To
      improve understanding of the genotype-phenotype correlations of prion gene
      mutations, clinical, genetic and neuropathological data were obtained from family
      members over 15 years. Six patients with the codon E200K mutation and 2 patients
      without the codon 200 mutation from this family were followed. The 6 patients
      with the codon 200 mutation had a mean age onset of 58.83 years (SD 7.2; lower 95
      % CI 51.0; upper 95 % CI 66.4). The most common symptoms at onset were memory
      loss, walking difficulties and hallucinations. The most frequent neurological
      phenomena were a rapidly progressive dementia, eye movement abnormalities and
      ataxia. The mean duration of onset of symptoms to death was 3.9 months (SD 1.1;
      lower 95 % CI 2.8; upper 95 % CI 5.1). Two male patients developed
      neurodegenerative disorders unrelated to the prion codon 200 mutation:
      progressive supranuclear palsy and olivopontocerebellar degeneration. Their mean
      survival was 96 months (SD 33.9; p < 0.0001). Individuals from families with the
      prion codon 200 mutation may have a rapidly progressive dementia. Members of
      families with inherited prion mutations may be at risk of other neurodegenerative
      disorders unrelated to the prion mutation.

PMID- 22584957
TI  - Successful rechallenge in two patients with BRAF-V600-mutant melanoma who
      experienced previous progression during treatment with a selective BRAF
      inhibitor.
AB  - The v-raf murine sarcoma viral oncogene homolog B1 (BRAF) gene is mutated at
      position 600 in about 50% of melanoma. Mutant BRAF activates the downstream
      effectors of the RAS-RAF-MEK-MAPK pathways and is a driver oncogene in these
      melanoma cells. Selective BRAF-V600 inhibitors (vemurafenib, dabrafenib) have
      high antitumor activity against BRAF-V600-mutant melanoma with objective tumor
      response rates. Resistance, however, develops within less than a year in the
      majority of patients. Several different mechanisms have been found to mediate
      acquired resistance, but these do not involve the occurrence of secondary
      mutations in the BRAF gene. Two patients with BRAF-V600E mutant melanoma who had
      documented progression during treatment with dabrafenib/GSK1120212 and
      dabrafenib, respectively, were rechallenged with dabrafenib and vemurafenib after
      a treatment-free interval of 8 and 4 months during which further progression was
      documented. Both patients showed a marked clinical response and, in both,
      objective tumor regression (qualifying as a mixed and a partial response
      according to RECIST) was documented. These two case observations indicate that
      resistance to BRAF-selective inhibitors can be reversible following treatment
      interruption.

PMID- 22584956
TI  - Risk of intracranial hemorrhage with anticoagulation therapy in melanoma patients
      with brain metastases.
AB  - Venous thromboembolism (VTE) is a frequent complication in melanoma patients with
      brain metastases (BM). The management of these patients is challenging because of
      the high risk of intracranial hemorrhage (ICH) and the limited data available on
      the safety of anticoagulation in this scenario. We reviewed the treatments and
      outcomes among melanoma patients with BM and VTE at our institution to determine
      the safety of anticoagulation in these patients. A retrospective chart review was
      performed to identify melanoma patients with BM who were diagnosed with VTE. The
      clinical characteristics of the BM and the VTE, the treatments given for VTE,
      subsequent ICH, and overall survival (OS) were determined. The characteristics
      and outcomes were compared between patients who received systemic anticoagulation
      and those who did not. A total of 74 evaluable melanoma patients with BM and VTE
      were identified. Fifty-seven (77%) patients received systemic anticoagulation.
      There was no significant difference in the number (P=0.40) or the maximum
      diameter (P=0.55) of brain metastasis between the patients who received
      anticoagulation and those who did not. Two (4%) patients who received
      anticoagulation developed ICH, which was not statistically different from the
      patients who did not receive anticoagulation (0%, P=1.00). There was a trend
      toward longer OS from VTE among patients who received systemic anticoagulation
      (median OS: 4.2 vs. 1.2 months, P=0.06). Anticoagulation for VTE did not
      significantly increase the risk of ICH or decrease OS in patients with melanoma
      BM. These data support the safety of systemic anticoagulation for VTE in these
      patients.

PMID- 22584958
TI  - Could forearm Kinesio Taping improve strength, force sense, and pain in baseball
      pitchers with medial epicondylitis?
AB  - OBJECTIVE: To determine short-term effects of applied forearm Kinesio Taping (KT)
      on pain, wrist flexor strength, and force sense for baseball players with medial
      epicondylitis (ME). DESIGN: Case-control repeated measures study. SETTING:
      Clinical sports medicine research laboratory in a medical university.
      PARTICIPANTS: A group of 10 baseball players with ME (ME group) and another group
      of 17 healthy collegiate athletes (healthy group). INTERVENTION: Three taping
      conditions were applied in both groups: (1) no taping applied, (2) placebo taping
      applied (PT), and (3) KT applied. MAIN OUTCOME MEASURES: Three variables were
      measured including maximal wrist flexor strength, related/absolute force sense
      errors, and pain scale (pressure pain and pain tolerance) under 3 taping
      conditions. RESULTS: No significant relationship was found either in maximal
      wrist flexor strength or in related force sense errors between the 2 groups with
      taping applied, except absolute force sense errors (P = 0.037). Both the healthy
      group and the ME group in absolute force sense measurement significantly
      decreased the errors in PT and KT conditions. Also, the tolerance of pressure
      pain also improved in both the healthy group and the ME group when performing PT
      and KT conditions. CONCLUSIONS: Forearm KT may enhance absolute force sense and
      improve pain condition for both healthy athletes and athletes suffering from ME
      when placebo and KT applied. However, KT did not result in significant changes in
      maximal wrist flexor strength for either group.

PMID- 22584959
TI  - Effects of lightweight outdoor clothing on the prevention of hypothermia during
      low-intensity exercise in the cold.
AB  - OBJECTIVE: To study protective effects of windbreaker jacket and pants during
      exercise in the cold. DESIGN: Randomized pilot study. SETTING: Climate chamber.
      PARTICIPANTS: Nine well-trained (V[Combining Dot Above]O2max 61.7 +/- 6.6
      mL/min/kg) sport students (6 male and 3 female participants). INTERVENTIONS:
      Subjects started walking for 1 hour in a climate chamber (0 degrees C ambient
      temperature and wind speed of 10 km/h) at 70% V[Combining Dot Above]O2max wearing
      gloves, a T-shirt, and shorts. Then, the walking speed was reduced to 30%
      V[Combining Dot Above]O2max for an additional 60 minutes or until core
      temperature dropped below 35.5 degrees C. Subsequently, 3 groups of 3
      participants continued walking without change of clothing or obtaining
      additionally a cap and a windbreaker jacket or windbreaker jacket and pants. MAIN
      OUTCOME MEASURES: Core and skin temperature, thermal comfort. RESULTS: The main
      findings of this study were that exercising at 70% V[Combining Dot Above]O2max in
      the cold was sufficient to prevent hypothermia and that during low-intensity
      exercise (30% V[Combining Dot Above]O2max), the combined use of a polyester cap,
      lightweight windbreaker jacket, and pants was necessary to increase a
      prehypothermic core temperature. CONCLUSIONS: We strongly recommend taking a cap,
      windbreaker jacket, and pants for the prevention of hypothermia during exhaustive
      walking or running in cold weather conditions.

PMID- 22584960
TI  - Frontal plane landing mechanics in high-arched compared with low-arched female
      athletes.
AB  - OBJECTIVE: To examine ground reaction forces (GRFs); frontal plane hip, knee, and
      ankle joint angles; and moments in high-arched (HA) and low-arched (LA) athletes
      during landing. DESIGN: Experimental study. SETTING: Controlled research
      laboratory. PARTICIPANTS: Twenty healthy female recreational athletes (10 HA and
      10 LA). INTERVENTIONS: Athletes performed 5 barefoot drop landings from a height
      of 30 cm. MAIN OUTCOME MEASURES: Frontal plane ankle, knee, and hip joint angles
      (in degrees) at initial contact, peak vertical GRF, and peak knee flexion; peak
      ankle, knee, and hip joint moments in the frontal plane. RESULTS: Vertical GRF
      profiles were similar between HA and LA athletes (P = 0.78). The HA athletes
      exhibited significantly smaller peak ankle inversion angles than the LA athletes
      (P = 0.01) at initial contact. At peak vertical GRF, HA athletes had
      significantly greater peak knee (P = 0.01) and hip abduction angles than LA
      athletes (P = 0.02). There were no significant differences between HA and LA
      athletes in peak joint moments (hip: P = 0.68; knee: P = 0.71; ankle: P = 0.15).
      CONCLUSIONS: These findings demonstrate that foot type is associated with altered
      landing mechanics, which may underlie lower extremity injuries. The ankle-driven
      strategy previously reported in female athletes suggests that foot function may
      have a greater relationship with lower extremity injury than that in male
      athletes. Future research should address the interaction of foot type and gender
      during landing tasks.

PMID- 22584961
TI  - Nerve entrapment after hamstring injury.
AB  - Hamstring muscle injuries are a frequent cause of athletic sequelae, and the
      frequency of reinjuries is high. Frequently, disability in sport is the
      consequence and performance is limited. A case report of a soccer player who was
      unable to play his sport after a minor hamstring muscle injury is presented. We
      introduce a previously undescribed lesion featured by a scar compromising a motor
      branch of the sciatic nerve to the long head of the biceps femoris muscle.
      Resection of the involved branch of the nerve resulted in complete pain relief
      and full sport capacity. This case report demonstrates that in very rare cases, a
      scar tissue-induced intramuscular entrapment of a branch of the sciatic nerve
      must be considered as a reason for athletic incapacity after minor hamstring
      injury. Both the degree of a muscular injury and its specific location within the
      injured muscle may therefore influence the functional outcome.

PMID- 22584962
TI  - Amnesia after a half marathon - a case study.
AB  - This is a description of a previously healthy female who developed a memory
      deficit after running a 21-km race for the first time in her life. The memory
      problem lasted a few hours, during which time she was anxious, asking the same
      questions repeatedly. The effects of exercise on memory are discussed. Transient
      global amnesia, its associations and prognosis, is reviewed.

PMID- 22584963
TI  - Hyponatremia is associated with higher NT-proBNP than normonatremia after
      prolonged exercise.
AB  - OBJECTIVE: To determine the incidence of and risk factors for exercise-associated
      hyponatremia (EAH) in cyclists completing a long-distance bike ride and to assess
      whether postexercise serum NT-proBNP concentration (brain natriuretic protein
      precursor) differed between riders with and without EAH. DESIGN: Observational
      study. SETTING: "Around the Bay in a Day" cycle event, October 2010.
      PARTICIPANTS: One hundred thirty-nine cyclists prospectively enrolled, with 90
      completing 210 or 250 km. MAIN OUTCOME MEASURES: Body weight change and fluid
      intake during the event, and postevent serum sodium concentration ([Na+]) and NT
      proBNP concentration ([NT-proBNP]). RESULTS: Four riders (4.5%) were hyponatremic
      ([Na+] < 135 mmol/L). The lowest postride [Na+] was 126 mmol/L. Hyponatremia was
      associated with a mean weight gain of 3.4 kg (3.9% of total body weight).
      Significant negative correlations were found between postride [Na+] and change in
      weight (r = -0.34; P < 0.01) and fluid intake when expressed as total volume (r =
      -0.35; P < 0.01), mL/kg body weight (r = 0.33; P < 0.01), mL.kg.h (r = -0.27; P <
      0.01), or mL/h (r = -0.29; P < 0.01). NT-proBNP concentrations levels in 3 of the
      4 hyponatremic subjects were markedly elevated compared with eunatremic subjects
      matched for age, sex, distance ridden, training, and medical history.
      CONCLUSIONS: Exercise-associated hyponatremia was found to occur in 4.5% of the
      study group and was associated with weight gain during a prolonged bike ride.
      Postride [Na+] varied inversely with weight change and with fluid intake. Three
      of 4 hyponatremic riders had significant elevations of [NT-proBNP]. These results
      support the hypothesis that overconsumption of hypotonic fluids in this setting
      is the most important cause of EAH.

PMID- 22584964
TI  - Bilateral stress fracture of the carpal scaphoid:  report in a child and review
      of the literature.
AB  - We describe a case of a bilateral stress fracture of the carpal scaphoid in a 13
      year-old boy. The patient played as a goalkeeper from the age of 5 years and
      presented with a 2-year history of intermittent pain in both wrists. Our patient
      underwent open reduction and bone grafting from the iliac crest in both wrists (6
      months apart). He subsequently became asymptomatic and resumed sport activities.
      This patient presented with what was considered a rare case of a stress fracture
      of both scaphoid bones secondary to repetitive dorsiflexed movements. The patient
      denied the presence of acute symptoms after a fall and did not perceive the onset
      of pain as being related to any trauma to the wrist, particularly while playing
      soccer. A review of other similar cases previously published is also presented.

PMID- 22584965
TI  - Metallomacrocycles as ligands: synthesis and characterisation of aluminium
      bridged bisglyoximato complexes of palladium and iron.
AB  - Dialuminiummacrocycles based on bisglyoximato moieties were prepared and their
      coordination chemistry with Fe(II) and Pd(II) was investigated. The bridging
      aluminium centers were supported by several types of tetradentate diphenoxide
      diamine ligands. The nature of the ancillary ligands bound to aluminium was found
      to affect the overall geometry and symmetry of the metallomacrocycles.
      Enantiopure, chiral diphenoxide ligands based on the (R,R)-trans-1,2
      diaminocyclohexane backbone afforded cleanly one metallomacrocycle isomer. The
      size and electronic properties of remote substituents on aluminium-bound ligands
      affected the binding mode and electronic properties of the central iron. A
      structurally characterized iron complex shows trigonal prismatic coordination
      mode, with phenoxide bridges between iron and aluminium. Increasing the size of
      the phenoxide substituents led to square bipyramidal coordination at iron.
      Employing p-NO(2)- instead of p-tBu-substituted phenoxide as supporting ligands
      for aluminium caused a 0.27 V positive shift of the Fe(III)/Fe(II) reduction
      potential. These results indicate that the present synthetic approach can be
      applied to a variety of metallomacrocycles based on bisglyoximato motifs to
      affect the chemistry at the central metal.

PMID- 22584966
TI  - Expression and functional coupling of liver beta2 - adrenoceptors in the human
      hepatocellular carcinoma.
AB  - AIM: Hepatocellular carcinoma (HCC) is one of the most common cancers and a
      leading cause of death worldwide. There are now multiple lines of evidence
      demonstrating that the beta-adrenoceptor ( beta-AR) signaling plays an important
      role in the progression and metastasis of cancer and may become a novel target
      for cancer therapy. Little information exists regarding the status of beta-ARs
      and their postreceptor intracellular signaling cascade in the development of
      human HCC. This study was conducted to detect the expression signal transduction
      of the beta-ARs in liver membranes obtained from patients with HCC and elucidate
      their possible implication on HCC development. METHODS: The beta-AR density and
      subtype distribution were determined by receptor binding studies. Protein levels
      of the beta(2)-AR and G(s)(alpha) protein were determined by Western blot
      analysis. The receptor coupling efficiency and biochemical activities of the
      adenylate cyclase(AC) was also determined. RESULTS: In HCC liver membranes, the
      beta(2)-AR density was higher than the density in the nonadjacent nontumor liver
      membranes. The beta(2)-AR protein expression was 1.5-fold increased as compared
      with nonmalignant controls, and positively correlated with the receptor density.
      The G s protein expression as well as the receptor, AC and G protein-stimulated
      activation of the cAMP formation was reduced in HCC. CONCLUSION: The beta(2)-AR
      was upregulated in human HCC. Despite this upregulation of the receptor,there was
      an altered postreceptor signal transduction in HCC liver. The mechanisms
      responsible for this change in the growth of HCC and the nature of this
      alteration remain unclear.

PMID- 22584967
TI  - George Fernand Widal (1862-1929): serologist and clinician-scientist.

PMID- 22584968
TI  - ECGs with small QRS voltages.
AB  - The causes of low voltage complexes on the electrocardiogram (ECG) are variable;
      however, they are not commonly discussed. An ECG with small QRS amplitudes may
      initially look unremarkable to the unwary, but some of the underlying conditions
      may be critical. Although imperfect, the ECG is still a useful, noninvasive and
      readily available tool for the screening of these underlying conditions. We
      present two cases with low voltage complexes in the ECG. The first case
      highlights how the findings on ECG and subsequent echocardiogram led to the
      diagnosis of a rare case of cardiac amyloidosis. In the second case, a screening
      electrocardiogram alerted the physicians to a life-threatening condition, that of
      a large pericardial effusion with cardiac tamponade.

PMID- 22584969
TI  - Infections of the deep neck spaces.
AB  - Deep neck infections (DNI) have a propensity to spread rapidly along the
      interconnected deep neck spaces and compromise the airway, cervical vessels and
      spinal canal. The value of imaging lies in delineating the anatomical extent of
      the disease process, identifying the source of infection and detecting
      complications. Its role in the identification and drainage of abscesses is well
      known. This paper pictorially illustrates infections of important deep neck
      spaces. The merits and drawbacks of imaging modalities used for assessment of
      DNI, the relevant anatomy and the possible sources of infection of each deep neck
      space are discussed. Certain imaging features that alter the management of DNI
      have been highlighted.

PMID- 22584970
TI  - Laparoscopic exploration can salvage failed endoscopic bile duct stone
      extraction.
AB  - INTRODUCTION: Conventionally, patients who failed endoscopic removal of common
      bile duct stones (CBDS) by endoscopic retrograde cholangiopancreaticography
      (ERCP) would be treated with open cholecystectomy and common bile duct
      exploration. Laparoscopic common bile duct exploration (LCBDE) is an established
      option for treating CBDS. The aim of this paper was to look at the feasibility of
      LCBDE as a salvage procedure after failed endoscopic stone extraction (ESE). The
      secondary endpoint was to examine the short-term outcomes of our LCBDE series.
      METHODS: We retrospectively reviewed a prospective database to study the
      feasibility of LCBDE as a salvage procedure for failed ERCP. RESULTS: Since its
      inception in 2006, 43 patients had undergone LCBDE at our centre. This was
      achieved via a transcystic approach in 25 patients and laparoscopic
      choledochotomy in 15 patients. There were three conversions. Of these 43
      patients, 21 had a pre-operative attempt at ESE, but only six patients had their
      ducts cleared endoscopically. The 15 patients who failed ESE underwent LCBDE, of
      which 14 achieved successful stone clearance and one required open conversion.
      One patient developed a bile leak, which resolved spontaneously. The median
      length of stay (LOS) for these 15 patients was three days, while the median LOS
      for the whole cohort was two days. CONCLUSION: LCBDE has been shown to be a safe
      and effective method for treating CBDS, with the added bonus of a short hospital
      stay. Where the expertise is available, LCBDE is a safe option as a salvage
      procedure for failed ESE.

PMID- 22584971
TI  - Chronic atrophic gastritis is a progressive disease: analysis of medical reports
      from Shanghai (1985-2009).
AB  - INTRODUCTION: We aimed to examine the turnover of chronic atrophic gastritis
      (CAG) pathologically and endoscopically and explore its potential causes.
      METHODS: A retrospective analysis was conducted of prospective data collected
      from 1,592 patients who underwent gastroscopy three times or more during the
      period 1985-2009 at Renji Hospital, Shanghai, China. Pathological and endoscopic
      findings were analysed. Data collected included gender, age, length of follow-up
      period, family history, past medical history, history of Helicobacter (H.) pylori
      infection, drug history for the use of proton pump inhibitors (PPIs), antacids
      and non-steroidal anti-inflammatory drugs [NSAIDs], and lifestyle history,
      including the patients' eating habits. RESULTS: 23 (1.44%) patients presented
      with gastric cancers resulting from CAG and 349 (21.92%) patients had dysplasia.
      Pathological and endoscopic findings suggested that the proportion of patients
      with worsening gastric mucosa during the atrophic and intestinal metaplasia (IM)
      phases was over 35% with increasing age. Gastric mucosa was found to be
      pathologically aggravated by carbonated drinks and fast food, and pathologically
      degenerated by H. pylori infection. Smoking deteriorated the gastric mucosa. Side
      dishes of vegetables may benefit the gastric mucosa even in the atrophic and IM
      phases. CONCLUSION: Our findings support the consensus that CAG is a progressive
      disease. Potential factors that were found to affect the state of the gastric
      mucosa in our patient group were gender, H. pylori infection, use of PPIs or
      NSAIDs, and intake of vegetable side dishes, spicy food, carbonated drinks and
      fast food.

PMID- 22584972
TI  - Anatomical variations of the internal jugular vein: implications for successful
      cannulation and risk of carotid artery puncture.
AB  - INTRODUCTION: Complications occur in over 15% of central venous cannulations,
      often a result of anatomical variations. This study aimed to determine the
      anatomical variations of the internal jugular vein (IJV), demonstrate the likely
      success of cannulation and assess the risk of carotid artery (CA) injury when
      catheterising the IJV using the external landmarks technique at various degrees
      of head rotation in the local population. METHODS: 100 elective cardiac surgical
      patients were prospectively enrolled. Simulated catheterisations were performed
      with patients placed in the Trendelenburg position. The standard landmark
      technique was used to identify anatomy. Simulations were done at six different
      degrees of rotation of the head: 0 degrees , 30 degrees  and 60 degrees  for both
      right and left IJVs. Difficult catheterisation was defined as an IJV diameter < 7
      mm. RESULTS: There was no thrombosed or absent IJV in any patient.
      Catheterisation was potentially difficult in 15% of patients at 30 degrees  head
      rotation and more difficult for the left IJV than the right (20% vs. 10%; p <
      0.05). The simulated needle hit the IJV in 82% of the attempts, but the needle
      was in the middle 80% of the vein only 70% of the time. Neck rotation increased
      the degree of overlap of the CA relative to the IJV from 20%-30% to 50%.
      CONCLUSION: Anatomical variations play a significant role in determining the
      success of IJV catheterisation as well as the incidence of catheterisation
      associated complications. This study emphasises the importance of using
      ultrasonography to guide IJV catheterisation, even in patients with seemingly
      normal neck anatomy.

PMID- 22584973
TI  - Coeliac trunk and its branches: anatomical variations and clinical implications.
AB  - INTRODUCTION: Knowledge of anatomical variations of the great vessels of the
      abdomen, including the coeliac trunk, is important for clinicians planning
      surgical intervention and radiological imaging. The present study aimed to record
      the prevalence of variations in the vascular pattern of branches of the coeliac
      trunk in cadavers. METHODS: A total of 50 properly embalmed and formalin-fixed
      cadavers from the Indian population were selected for the study. Dissection
      included surgical incision, followed by mobilisation of the anatomical viscera,
      to observe and record the branching pattern of the coeliac trunk. RESULTS: The
      left gastric, common hepatic and splenic arteries were found to arise from the
      coeliac trunk in 86% of cadavers. In 76% of cadavers, the origin of the gastric
      artery was proximal to the bifurcation of the coeliac trunk into the common
      hepatic and splenic arteries. In one case, all three branches arose directly from
      the abdominal aorta, and the origin of the splenic artery was 1 cm distal to the
      origin of the left gastric and common hepatic arteries. In another case, the
      common hepatic and left gastric arteries arose from the coeliac trunk, and the
      origin of the splenic artery was 1.5 cm distal to the abdominal aorta.
      CONCLUSION: Vessel ligation and anastomosis are important in surgical procedures
      like liver transplantation, and background knowledge of the different vascular
      patterns of branches of the coeliac trunk is vital. The findings of our study
      could help to minimise complications related to abdominal surgery, including
      bleeding and necrosis, and facilitate better and more accurate radiological
      interpretations.

PMID- 22584974
TI  - Correlation between lymphangiogenesis and clinicopathological parameters in renal
      cell carcinoma.
AB  - INTRODUCTION: Lymphangiogenesis has been reported to be important in the
      prognosis of several tumours. The aim of this study was to assess the correlation
      between lymphangiogenesis and clinicopathological prognostic parameters in
      patients with clear cell renal cell carcinoma. METHODS: 62 patients with renal
      cell carcinoma were included in the study. The D2-40 antibody, assessed
      immunohistochemically for each patient, was used as a marker. Light microscopy
      was used to determine the presence of intratumoral lymphatic vessels (ILVs) and
      the number of peritumoral lymph vessels (PLVs)/mm2 or PLV density (PLVD).
      Correlation between the numbers and the Fuhrman nuclear grade, tumour stage,
      distant metastasis status, presence of lymph node metastasis and lymphovascular
      invasion was assessed. RESULTS: A significant correlation was found between the
      presence of ILVs and distant metastasis (p = 0.033) and lymph node metastasis (p
      = 0.024). However, no significant correlation was found between the Fuhrman
      nuclear grade (p = 0.553), tumour stage (p = 0.464) and lymphovascular invasion
      (p = 0.242). Mean PLVD was 20.8, and no significant difference was found between
      the patients with PLVD below average and those with PLVD above average in terms
      of distant metastasis (p = 0.337), lymph node metastasis (p = 0.792), the Fuhrman
      nuclear grade (p = 0.566), tumour stage (p = 0.795) and lymphovascular invasion
      (p = 0.942). CONCLUSION: We found a significant correlation between ILVs and
      lymph node and distant metastases in patients with renal cell carcinoma.

PMID- 22584975
TI  - Factors affecting survival of patients with oesophageal cancer: a study using
      inverse Gaussian frailty models.
AB  - INTRODUCTION: Oesophageal cancer is one of the most common causes of cancer
      mortality in developing countries, including Iran. This study aimed to assess
      factors affecting survival of patients with oesophageal cancer using parametric
      analysis with frailty models. METHODS: Data on 359 patients with oesophageal
      cancer was collected from the Babol Cancer Registry for the period 1990-1991. By
      2006, the patients had been followed up for a period of 15 years. Hazard ratio
      was used to interpret the risk of death. To explore factors affecting the
      survival of patients, log-normal and log-logistic models with frailty were
      examined. The Akaike Information Criterion (AIC) was used for selecting the best
      model(s). Cox regression was not suitable for this patient group, as the
      proportionality assumption of the Cox model was not satisfied by our data (p =
      0.007). RESULTS: Multivariate analysis according to parametric models showed that
      family history of cancer might increase the risk of death from cancer
      significantly. Based on AIC scores, the log-logistic model with inverse Gaussian
      frailty seemed more appropriate for our data set, and we propose that the model
      might prove to be a useful statistical model for the survival analysis of
      patients with oesophageal cancer. The results suggested that gender and family
      history of cancer were significant predictors of death from cancer. CONCLUSION:
      Early preventative care for patients with a family history of cancer may be
      important to decrease the risk of death in patients with oesophageal cancer. Male
      gender may be associated with a lower risk of death.

PMID- 22584976
TI  - Letting the cat out of the bag: shifting practices of cancer disclosure in
      Singapore.
AB  - INTRODUCTION: Communication between patients and physicians is crucial in the
      disclosure of cancer diagnosis. Although westernisation of Asian societies has
      resulted in increased awareness of patient autonomy, the family continues to play
      an important influencing role in the disclosure process. Therefore, in this
      study, we aimed to characterise the experience of physicians with the disclosure
      of cancer diagnosis in a westernised Asian population. METHODS: Oncologists at a
      tertiary hospital were approached to participate in this study. Information
      pertaining to the extent and approach to disclosure was collated. Logistic
      regression analysis was performed to characterise factors pertaining to the
      willingness of physicians to fully disclose a diagnosis of cancer. RESULTS: In
      all, 25 oncologists (mean age 38 years; 72% men) responded to the survey. A
      majority of oncologists disclosed a cancer diagnosis directly to the patient over
      the first few visits. The main reason behind partial or non-disclosure was family
      objection. Ordinal logistic regression analysis showed that family resistance was
      the only significant predictor of reluctance to disclose a cancer diagnosis (p =
      0.01). CONCLUSION: In this pilot study, contrary to previous reports, we found
      that oncologists were more likely to disclose a diagnosis of cancer to the
      patient first, that they do not accede fully to the family's request for non
      disclosure and that family resistance was the only significant predictor of
      reluctance to disclose a diagnosis of cancer.

PMID- 22584977
TI  - Afebrile seizure subsequent to initial febrile seizure.
AB  - INTRODUCTION: Febrile seizure (FS) is the most common paediatric neurological
      problem. The purpose of this study was to determine the frequency of afebrile
      seizures subsequent to FS in children with initial FS and to evaluate its risk
      factors. METHODS: A prospective study was conducted on all children (age 6 months
      to 6 years) referred with initial FS to the Shahid Sadoughi Hospital, Yazd, Iran,
      between August 2004 and March 2006, who were followed up for at least 15 months
      for the occurrence of subsequent afebrile seizures. RESULTS: 161 boys and 120
      girls (mean age 2.12 +/- 1.33 years) were followed up for 34.1 +/- 7.8 months. 87
      (31%) patients had complex FS and 19 (6.7%) patients had subsequent afebrile
      seizure, with a mean occurrence time of 10.6 +/- 6.4 months. Univariate analysis
      using chi-square test showed that initial FS within one hour of developing fever
      (p = 0.0001), neurodevelopmental delay (p = 0.0001), family history of epilepsy
      (p = 0.0001), recurrent FS (p = 0.003) and focal FS (p = 0.04) were risk factors
      for subsequent afebrile seizure. On multivariate analysis, neurodevelopmental
      delay (odds ratio [OR] 2.6, 95% confidence interval [CI] 2.3-3.4), initial FS
      within one hour of developing fever (OR 1.7, 95% CI 1.2-2.1) and family history
      of epilepsy (OR 1.5, 95% CI 1.1-1.9) were significant factors. CONCLUSION:
      Special attention should be paid to children with FS during history-taking and
      developmental assessments to identify high-risk patients and those who might need
      prophylactic anticonvulsants.

PMID- 22584978
TI  - Procalcitonin and minimal-change nephropathy: a pilot study.
AB  - INTRODUCTION: This study assessed the role of procalcitonin (PCT) in the
      differentiation of minimal-change nephropathy (MCN) relapses from infections co
      existent with proteinuria flares in children. METHODS: Data on the PCT levels of
      patients with MCN who were on follow-up were retrospectively gathered at relapse
      (Group I), during proteinuria attacks co-existent with intercurrent infection
      (Group II) and at remission (Group III). The results of these three groups were
      then prospectively compared with nephrologically healthy patients who had
      infections that were similar to those in Group II (Group IV), and controls (Group
      V). RESULTS: Significant differences in PCT level were noted between patients of
      Groups I, II and IV and the other two groups. A 93% reduction in proteinuria was
      achieved for Group II patients following an antibiotic regimen. The difference in
      PCT level between Groups I and II was significant. PCT showed a higher diagnostic
      predictability than C-reactive protein (CRP) in Group I patients, and was as good
      as CRP for those with infection and infection-related proteinuria. Sensitivity *
      specificity in relapse and infection-related states for PCT were 0.472 and 0.628,
      respectively, and those for CRP were 0.183 and 0.762, respectively. CONCLUSION: A
      combined approach with CRP and PCT readings may be beneficial in discriminating
      proteinuria attacks co-existent with intercurrent infection from sole relapses of
      nephrotic syndrome. PCT may be a part of the wide spectrum of immune
      abnormalities seen in patients with MCN.

PMID- 22584979
TI  - Opioid-induced hyperalgesia: a review of epidemiology, mechanisms and management.
AB  - There has been a growing interest in opioid-induced hyperalgesia (OIH), which is
      an increased sensitivity to pain caused by opioid exposure. Multiple underlying
      pathways may contribute to the development of OIH, and the mechanism may vary
      with the duration of opioid exposure, dose, type and route of administration. In
      addition, the distinction between OIH, tolerance and withdrawal should be made in
      both the basic and clinical science literature so as to help translate findings
      to the clinical phenomenon and to help determine the best strategies to prevent
      or treat OIH.

PMID- 22584981
TI  - Malaysian internship a reflection of undergraduate training: time to go back to
      basics.

PMID- 22584984
TI  - Reversible recurrent laryngeal nerve palsy in acute thyroiditis.
AB  - First reported by Nager in 1927, unilateral vocal cord paralysis associated with
      thyroid disease suggests the malignant and irreversible nature of the thyroid
      lesion. This condition is rarely seen in benign thyroid diseases, and the
      function of the vocal cord does not usually return. We present a 54-year-old
      woman with a history of right hemithyroidectomy for benign thyroid nodule, who
      had an episode of subacute thyroiditis associated with unilateral vocal cord
      paralysis. The patient was treated with intravenous antibiotics and underwent a
      completion thyroidectomy. Post operation, her vocal cord function recovered
      successfully. Unilateral vocal cord paralysis can be seen in thyroiditis, and
      this can be reversed with steroids and antibiotics. If surgery is necessary, care
      must be taken to preserve the recurrent laryngeal nerve.

PMID- 22584985
TI  - Understanding maternal mental illness: psychiatric autopsy of a maternal death.
AB  - Maternal mental illness is a significant public health concern, with established
      adverse outcomes on both mother and infant, such as impaired mother-infant
      bonding and infant cognitive and emotional development. In severe cases, maternal
      mortality and infanticide can tragically occur. This is a report on the suicide
      of a mother who jumped to her death at three months postpartum. She suffered from
      puerperal psychosis with bipolar features, with onset at six weeks postpartum.
      The case highlights the burden of maternal mental illness in our community as
      well as the need for resources and services to care well for mothers. With a
      better understanding of its presentation and risk factors, early identification
      and intervention can reduce morbidity and mortality.

PMID- 22584986
TI  - Successful treatment of peritonitis by C. bertholletiae in a chronic kidney
      failure patient on continuous ambulatory peritoneal dialysis after kidney
      rejection.
AB  - Peritonitis is a common problem in patients undergoing peritoneal dialysis.
      However, peritonitis due to Cunninghamella (C.) bertholletiae, a fungus of the
      class Zygomycetes, is rare. We present a case of fungal peritonitis in a patient
      on continuous ambulatory peritoneal dialysis due to kidney rejection. Direct
      examination of the patient's peritoneal fluid showed fungal hyphae, and the
      culture was identified as C. bertholletiae. A cumulative dose of 1,600 mg
      fluconazole was given to the patient intraperitoneally over a one-week period.
      When his condition had stabilised, oral antifungal treatment was administered for
      two weeks. After removal of the Tenckhoff catheter, the patient was discharged
      with arteriovenous fistulation for haemodialysis. Zygomycosis due to C.
      bertholletiae is often fatal and non-responsive to systemic antifungal therapy.
      This case is the first from India with a successful outcome, and highlights the
      importance of early detection and intervention for successful outcome of
      peritonitis caused by C. bertholletiae.

PMID- 22584987
TI  - Angiographic and intravascular ultrasonographic features of Kawasaki coronary
      artery disease.
AB  - We report a 38-year-old man with previous Kawasaki disease who presented with
      exertional dyspnoea and was found to have multivessel coronary aneurysm and
      stenoses on coronary angiography. Coronary artery bypass surgery was subsequently
      performed. This case highlights the angiographic and intravascular
      ultrasonographic imaging features of this relatively uncommon condition
      presenting to an adult general cardiology service in Singapore.

PMID- 22584988
TI  - Hybrid surgical management of a saccular aneurysm of the internal jugular vein.
AB  - Internal jugular vein saccular aneurysms are rare. Surgical management is
      indicated when there is a risk of rupture. We recommend a hybrid procedure
      combining endovascular and open techniques. We report the case of a 77-year-old
      female patient with a saccular aneurysm of the internal jugular vein, which was
      excised with combined endovascular and vascular techniques.

PMID- 22584989
TI  - Allgrove syndrome.
AB  - Allgrove syndrome is a rare autosomal recessive disorder. It is also known as the
      3A syndrome and characterised by the triad of achalasia, alacrima and adrenal
      insufficiency. The AAAS gene is encoded on chromosome 12q13. We report the case
      of a 23-year-old woman who presented at the hospital with adrenal crisis that was
      triggered by infection of the urinary system and gastrointestinal bleeding. She
      had a known diagnosis of achalasia for eight years, and ophthalmologic
      examination revealed alacrima. Based on our findings, the patient was diagnosed
      with Allgrove syndrome.

PMID- 22584990
TI  - Tracheal schwannoma as a mimic of bronchial asthma.
AB  - Primary tracheal tumours are rare and less frequently observed than bronchial
      tumours. Primary neurogenic tumours of the trachea as schwannomas or
      neurilemmomas are extremely uncommon. We report a tracheal schwannoma in a female
      patient who presented with breathlessness and wheeze, and she was being treated
      for asthma. Flexible bronchoscopy revealed a large pedunculated tracheal mass and
      biopsy confirmed schwannoma. She was treated with laser ablation with partial
      reduction of the tumour. Subsequently, she was lost to follow-up, although
      resection of the tumour with tracheal reconstruction was planned.

PMID- 22584991
TI  - Short-term outcome after resection of neurogenic heterotopic ossification around
      the hips and elbow following encephalitis.
AB  - Heterotopic ossification (HO) is a potential complication following brain or
      spinal cord injuries and diseases. Post-encephalitis HO is rare, and the number
      of affected joints is a prognostic predictor. A literature review revealed only a
      limited number of such cases, with one or two anatomical regions affected in each
      case. We report the case of a 21-year-old man who developed HO at the peri
      articular regions of both hips and the right elbow post encephalitis. He had good
      functional outcome following excision of the ossific masses. There has not been
      any recurrence for up to two years from the first surgery. To the best of our
      knowledge, this is the first such case involving more than two anatomical
      regions, and the first reported case from Sri Lanka.

PMID- 22584992
TI  - Hyaluronate carboxymethylcellulose-based bioresorbable membrane (Seprafilm)
      reduces adhesion under the incision to make unplanned re-laparotomy safer.
AB  - PURPOSE: Hyaluronate carboxymethylcellulose-based bioresorbable membrane (HC
      membrane; Seprafilm((r))) is used to prevent postoperative adhesion. We conducted
      this study to assess the effectiveness of the HC membrane in reducing the
      severity of adhesions in patients undergoing unplanned re-laparotomy. METHODS:
      Between February, 2002 and December, 2010, 123 patients underwent abdominal
      surgery followed by a re-laparotomy in Kumamoto Regional Medical Center. The HC
      membrane was placed under the first abdominal incision in 60 patients (HC
      membrane group), whereas it was not used in the other 63 patients (control
      group). We compared the medical and operative records of these two groups.
      RESULTS: At the second laparotomy, adhesion under the incision was severe in many
      of the control group patients, but was significantly reduced in the HC membrane
      group. Postoperative small-bowel obstruction was significantly less frequent in
      the HC membrane group. According to univariate analysis of the risk factors for
      adhesion, prolonged operation time, blood loss, and not using an HC membrane were
      significantly associated with severe adhesion. Multivariate analysis revealed
      that only not using the HC membrane was significant. CONCLUSION: The HC membrane
      effectively reduces the severity of wound adhesion, making unplanned repeated
      laparotomy safer.

PMID- 22584994
TI  - Comment on Kanis et al.: Pitfalls in the external validation of FRAX.

PMID- 22584995
TI  - Pitfalls in the external validation of FRAX: response to Bolland et al.

PMID- 22584997
TI  - Mild iron overload in an African American man with SLC40A1 D270V.
AB  - We report on a 46-year-old black man who resided in Alabama with normal
      transferrin saturation, mild hyperferritinemia, chronic hepatitis C, and 3+ iron
      in hepatocytes and Kupffer cells. Exome sequencing revealed heterozygosity for
      SLC40A1 D270V (exon 7, c.809A->T), a mutation previously reported only in 1 black
      patient with iron overload who resided in the Republic of South Africa. The
      present patient was also heterozygous for: heme transporter FLVCR1 novel allele
      P542S (exon 10, 1624C->T); FLVCR1 T544M (rs3207090); hemopexin (HPX) R371W
      (rs75307540); ferritin scavenger receptor (SCARA5) R471H (rs61737287); and
      transferrin receptor (TFRC) G420S (rs41295879). He had no HFE, TFR2,HJV, or HAMP
      mutations. D270V was not detected in 19 other African Americans with iron
      overload who resided in Alabama. The allele frequency of SLC40A1 D270V in 258
      African American adults who participated in a health appraisal clinic was 0.0019
      (95% confidence interval 0-0.0057). D270V could explain 'classical' ferroportin
      hemochromatosis phenotypes in some African Americans.

PMID- 22584998
TI  - Microfluidic synthesis of multifunctional Janus particles for biomedical
      applications.
AB  - Multifunctional Janus particles have a variety of applications in a wide range of
      fields. However, to achieve many of these applications, high-throughput, low-cost
      techniques are needed to synthesize these particles with precise control of the
      various structural/physical/chemical properties. Microfluidics provides a unique
      platform to fabricate Janus particles using carefully controlled liquid flow in
      microfluidic channels to form Janus droplets and various types of solidification
      methods to solidify them into Janus particles. In this Focus article, we
      summarize the most recent representative works on Janus particle fabrication in
      microfluidics. The applications of Janus particles in biomedical areas are
      emphasized. We believe that microfluidics-enabled multifunctional Janus particles
      could resolve multiple prevalent issues in biomedicine (e.g., disease monitoring
      at an early stage, high-throughput bioassays, therapeutic delivery) if persistent
      effort and collaboration are devoted to this direction.

PMID- 22584999
TI  - Pancreatic cancer: Mouse models link metabolism and deubiquitination with Kras.

PMID- 22585000
TI  - Genetics: Understanding the ABSOLUTE genome.

PMID- 22585001
TI  - Gynaecological cancer: OCEANS' three: the ovarian job.

PMID- 22585003
TI  - Gastrointestinal cancer: Less is more for surgical treatment of oesophageal
      cancer.

PMID- 22585004
TI  - Biology and control of the red palm mite, Raoiella indica: an introduction.

PMID- 22585005
TI  - Ticks (Acari: Ixodidae) associated with small terrestrial mammals in the state of
      Minas Gerais, southeastern Brazil.
AB  - From June 2005 to November 2010, 43 small mammals encompassing 6 species of
      Didelphimorphia, 8 species of Rodentia, and 1 species of Lagomorpha were found
      parasitized by ticks in the state of Minas Gerais, southeastern Brazil. Nine tick
      species, in total 186 specimens, were identified as follows: Amblyomma cajennense
      (larvae and nymphs) on opossums and rodents; Amblyomma ovale (nymphs) on rodents;
      Amblyomma parvum (nymphs) on rodents; Amblyomma coelebs (nymphs) on opossums;
      Amblyomma dubitatum (nymph) on opossums; Ixodes amarali (females, nymphs, and
      larvae) on opossums and rodents; Ixodes loricatus (male, females, nymph) on
      opossums; Ixodes schulzei (female) on rodents; and Haemaphysalis leporispalustris
      (female) on rabbits. Most of the tick-host associations found in the present
      study have never been recorded in the literature; those include three new host
      records for I. amarali, four for A. cajennense, one for A. dubitatum, two for A.
      ovale, and one for A. coelebs. In addition, we provide the first record of A.
      coelebs in the state of Minas Gerais.

PMID- 22585002
TI  - Targeting ALK in neuroblastoma--preclinical and clinical advancements.
AB  - Despite improvements in cancer therapies in the past 50 years, neuroblastoma
      remains a devastating clinical problem and a leading cause of childhood cancer
      deaths. Advances in treatments for children with high-risk neuroblastoma have,
      until recently, involved addition of cytotoxic therapy to dose-intensive
      regimens. In this era of targeted therapies, substantial efforts have been made
      to identify optimal targets for different types of cancer. The discovery of
      hereditary and somatic activating mutations in the oncogene ALK has now placed
      neuroblastoma among other cancers, such as melanoma and non-small-cell lung
      cancer (NSCLC), which benefit from therapies with oncogene-specific small
      molecule tyrosine kinase inhibitors. Crizotinib, a small-molecule inhibitor of
      ALK, has transformed the landscape for the treatment of NSCLC harbouring ALK
      translocations and has demonstrated activity in preclinical models of ALK-driven
      neuroblastomas. However, inhibition of mutated ALK is complex when compared with
      translocated ALK and remains a therapeutic challenge. This Review discusses the
      biology of ALK in the development of neuroblastoma, preclinical and clinical
      progress with the use of ALK inhibitors and immunotherapy, challenges associated
      with resistance to such therapies and the steps being taken to overcome some of
      these hurdles.

PMID- 22585006
TI  - Squamous cell carcinoma of the lung invaded to esophagus: a case report of
      successful surgical treatment after preoperative transesophageal echographic
      evaluation.
AB  - We describe a successful surgical case of a 78-year-old man with a squamous cell
      carcinoma of the lung invaded to the esophagus. Chest computed tomography on
      admission showed a tumor mass shadow in the left lower lobe (S(6)). The tumor was
      adjacent to the esophagus, which was a strongly suspected lung cancer with
      esophageal invasion. We performed the transesophageal endoscopic ultrasound (EUS)
      for a detailed evaluation of the degree of invasion, and we obtained the findings
      of localized tumor invasion into the muscular coat of the esophagus. The tumor
      invaded to the esophagus perioperatively, and we could remove all the involved
      area with enough surgical margin. We believe that the preoperative evaluation
      using EUS is a useful procedure, if we suspect the lung cancer with esophageal
      invasion.

PMID- 22585007
TI  - Gender influence in isolated coronary artery bypass graft surgery: a propensity
      match score analysis of early outcomes.
AB  - INTRODUCTION: The female gender has been shown as high-risk factor for mortality
      and morbidity. We sought to assess the influence of female gender on coronary
      artery bypass graft (CABG) surgery from our own experience. METHODS: This is a
      retrospective analysis of prospectively collected database from a single centre.
      Patients were grouped according to gender and potential differences in pre
      operative, intra-operative and post-operative factors were explored. Significant
      high-risk factors were then fitted in a multivariate model to account for
      differences in predicting gender influence on surgical outcomes. RESULTS: Two
      thousand eight hundred and four consecutive patients underwent isolated first
      time CABG between February 2000 and December 2008; 562 (20%) patients were
      females. Pre-operatively, females were more likely to have significant
      comorbidities (age, congestive cardiac failure, hypercholesterolemia,
      hypertension, ischemic heart disease, peripheral vascular disease, pre-op
      arrhythmias, small body surface area and poor ejection fraction (p < 0.001))
      consistent with higher Euroscore (p > 0.0001) and more urgent surgery (p <
      0.002). Intra-operatively, they showed less extent pattern of disease requiring
      less bypass and cross-clamp time (p < 0.001). Observed surgical mortality was
      significantly higher in females (3.6 vs. 2.1%, p < 0.042); however, after
      adjusting for propensity score and significant factors identified in multivariate
      models, females only independently predicted a higher wound infection, lower
      neurological complications, lower rate of re-sternotomy, longer hospital stay and
      post-surgery stay (p < 0.01). CONCLUSIONS: Despite higher risk profile and higher
      observed surgical mortality, early outcomes in females were similar to their
      matched males' counterpart in isolated CABG surgery. Females were associated with
      higher incidence of wound infections but lower rate of neurological
      complications.

PMID- 22585008
TI  - The electrochemistry of CVD graphene: progress and prospects.
AB  - The unique electronic properties of graphene, a one atom thick carbon layer, were
      reported by scientists in 2004. Since this time graphene has subsequently been
      found to display several more unique and fascinating electrical, optical and
      mechanical properties. One particular area in which graphene has reportedly made
      an impact is in the field of electrochemistry, such as in providing enhancements
      in energy storage/generation and electrochemical sensing applications. Since
      2005, when graphene was shown to be fabricated by the so-called 'Scotch tape
      technique' where multiple layers of graphene are peeled from a slab of Highly
      Ordered Pyrolytic Graphite using adhesive tape and transferred onto an
      appropriate substrate, other fabrication methodologies of graphene have emerged.
      In the majority of cases, graphene is produced and supplied in solution, such
      that graphene has to be immobilised onto the desired surface. A fabrication
      process where graphene is grown upon a substrate and is ready for implementation
      is the Chemical Vapour Deposition (CVD) of graphene. In this perspective article
      we overview recent developments in the fabrication of CVD graphene and explore
      its utilisation in electrochemistry, considering its fundamental understanding
      through to applications in sensing and energy related devices.

PMID- 22585009
TI  - Unprocessed real-time imaging of vitreoretinal surgical maneuvers using a
      microscope-integrated spectral-domain optical coherence tomography system.
AB  - BACKGROUND: We have recently developed a microscope-integrated spectral-domain
      optical coherence tomography (MIOCT) device towards intrasurgical cross-sectional
      imaging of surgical maneuvers. In this report, we explore the capability of MIOCT
      to acquire real-time video imaging of vitreoretinal surgical maneuvers without
      post-processing modifications. METHODS: Standard 3-port vitrectomy was performed
      in human during scheduled surgery as well as in cadaveric porcine eyes. MIOCT
      imaging of human subjects was performed in healthy normal volunteers and
      intraoperatively at a normal pause immediately following surgical manipulations,
      under an Institutional Review Board-approved protocol, with informed consent from
      all subjects. Video MIOCT imaging of live surgical manipulations was performed in
      cadaveric porcine eyes by carefully aligning B-scans with instrument orientation
      and movement. Inverted imaging was performed by lengthening of the reference arm
      to a position beyond the choroid. RESULTS: Unprocessed MIOCT imaging was
      successfully obtained in healthy human volunteers and in human patients
      undergoing surgery, with visualization of post-surgical changes in unprocessed
      single B-scans. Real-time, unprocessed MIOCT video imaging was successfully
      obtained in cadaveric porcine eyes during brushing of the retina with the Tano
      scraper, peeling of superficial retinal tissue with intraocular forceps, and
      separation of the posterior hyaloid face. Real-time inverted imaging enabled
      imaging without complex conjugate artifacts. CONCLUSIONS: MIOCT is capable of
      unprocessed imaging of the macula in human patients undergoing surgery and of
      unprocessed, real-time, video imaging of surgical maneuvers in model eyes. These
      capabilities represent an important step towards development of MIOCT for
      efficient, real-time imaging of manipulations during human surgery.

PMID- 22585010
TI  - Venous thromboembolism in patients with Cushing's syndrome: need of a careful
      investigation of the prothrombotic risk profile.
AB  - A high incidence of venous thromboembolic (VTE) complications has been reported
      in Cushing's syndrome (CS), mostly post-operatively and attributable to
      hypercoagulability. The prevalence of symptomatic VTE was investigated
      retrospectively in 58 consecutive CS patients in relation to acquired and genetic
      thrombotic risk factors. Eight CS patients (14 %) developed VTE (group A), 3 of
      them related and 5 unrelated to surgery. These patients had higher urinary free
      cortisol (p = 0.01) and VWF levels (p = 0.02) than the 50 patients without VTE
      (group B), as well an increase in the hemostatically more efficient, high
      molecular-weight VWF multimers (p = 0.002). Factor V Leiden and the prothrombin
      gene 20210A variants (the most common inherited thrombophilic defects) were more
      represented in group A than in group B, as was the genotype GCAG/GCAG of the VWF
      gene promoter, known to hyperinduce VWF upregulation under cortisol excess. All
      but one of the patients with VTE unrelated to surgery had at least four acquired
      and at least one inherited risk factor. Severe hypercortisolism and VWF levels
      with increased haemostatic activity are strongly associated with VTE in CS. VTE
      episodes unrelated to surgery are attributable to the synergistic action of
      acquired and inherited thrombotic risk factors. Based on these observations, we
      believe that severely affected CS patients should be screened for coagulation
      disorders and receive antithrombotic prophylaxis whenever they have concomitant
      prothrombotic risk factors.

PMID- 22585011
TI  - Clinical factor 2011.

PMID- 22585013
TI  - National Clinical Guideline for adult care - so what?

PMID- 22585014
TI  - Early infant nutrition: the  importance of getting it right.

PMID- 22585012
TI  - Effects of mindfulness-based stress reduction on distressed (type D) personality
      traits: a randomized controlled trial.
AB  - Distressed ('Type D') personality, the combination of negative affectivity (NA)
      and social inhibition (SI), has been associated with adverse health outcomes. The
      purpose of this study was to examine if an 8-week mindfulness-based stress
      reduction (MBSR) program could reduce Type D personality characteristics.
      Distressed individuals from the Dutch general population (N = 146; mean age =
      46.07; 69 % female) participated in a randomized trial comparing the mindfulness
      intervention with waitlist control. Although change in Type D caseness did not
      differ between groups, the intervention group showed stronger reductions for both
      NA (p < .001) and SI (p < .05) dimensions, even when change in state negative
      affect was statistically controlled. These effects were mediated by change in
      self-reported mindfulness. In conclusion, MBSR may reduce characteristics of the
      distressed personality type, likely through the mechanism of increased
      mindfulness. 

PMID- 22585016
TI  - Any qualified provider and its role in bladder and bowel care.
AB  - The Department of Health's Any Qualified Provider (AQP) policy blindsided
      specialist continence services in 2011. Continence AQP services, once qualified,
      can bid to provide additional continence services to areas in the country where
      local commissioners have decided they would like competition in the local area to
      give patients greater choice in service provision and drive up clinical
      standards. This short article looks at this subject in more depth.

PMID- 22585015
TI  - Key considerations  of intermittent catheterisation.
AB  - Intermittent catheterisation provides a safe and effective alternative to
      indwelling catheterisation for patients who require bladder drainage. It can be
      undertaken by health professionals in a variety of clinical settings for a range
      of clinical indications, and increasingly by patients themselves who use it as a
      long-term bladder management technique. The relative simplicity of the technique
      comes with the potential for health professionals to underestimate the skills
      required when considering a regimen of intermittent catheterisation and, perhaps
      more importantly, to underestimate the impact it may have on individual patients.
      The aim of this article is to consider intermittent catheterisation, its
      indications as a bladder management technique, and the potential psychological
      impact it may have on the patient, as well as how this may influence concordance.

PMID- 22585017
TI  - Incontinence-associated dermatitis: protecting the older person.
AB  - As the older population in the UK continues to grow, so too will the number of
      people presenting with dermatological problems. Older people's skin is subject to
      dehydration internally and environmental factors externally. If, in addition, the
      individual suffers continence problems, he or she is at risk of painful
      incontinence-associated dermatitis, or even formation of a moisture lesion. The
      use of an effective barrier cream that gives protection while not interfering
      with continence pad efficacy can be an invaluable means of comfort to the older
      person.

PMID- 22585018
TI  - Sweat and tears: treating the patient with primary hyperhidrosis.
AB  - Hyperhidrosis is a distressing disorder characterised by excessive sweating.
      Whereas some cases are secondary to underlying conditions, primary hyperhidrosis
      is the more common form affecting around 3% of the population. Typically starting
      in childhood or adolescence, primary hyperhidrosis has a significant impact on an
      individual's quality of life and self-esteem, which is similar to that of more
      well recognised skin conditions, such as psoriasis, severe pruritus and acne.
      Treatment options for primary hyperhidrosis are varied, including topical
      treatments, Botulinum toxin A, systemic medication, iontophoresis and surgery;
      however, each method has drawbacks that are discussed in this article. Case
      examples within the article illustrate the potential of several of these
      treatments. Particular issues surrounding the treatment of children and
      adolescents with this condition are also discussed.

PMID- 22585019
TI  - Effectiveness of the new  NMC mentor preparation course.
AB  - This study aimed to determine whether the mentor preparation course introduced in
      2006 by the Nursing and Midwifery Council (NMC) and based on NMC mentor standards
      is meeting the needs of mentors to support preregistration students in practice.
      A cross-sectional survey was carried out, involving 346 mentors who successfully
      completed the new course. A self-administered postal questionnaire was used to
      collect data between December 2010 and February 2011, with a response rate of
      57.5%. Overall, respondents felt adequately prepared for their role as mentors
      and were more confident in their ability to support preregistration students in
      practice. However, a significant number of respondents received little protected
      time away from clinical duties to complete the theoretical and practical
      components of the course and many indicated the need for more input on the
      practice assessment document used for assessing preregistration nursing and
      midwifery students.

PMID- 22585020
TI  - Student nurses' personality traits and the nursing profession: part 1.
AB  - Individuals' attitudes stem partly from their personality traits, which may
      influence their interpersonal relationships with patients. Although personality
      traits are somewhat genetically determined, research has found that there are
      other factors, which may influence this, such as self-esteem, family, social and
      clinical environments and education. Part one of this article presents the
      methodology of a cross-sectional descriptive study that assessed the personality
      traits of two cohorts (n=116) of nursing/midwifery students aged 19-44 years
      (mean=21.5) in their third year of the nursing diploma/BSc (Hons) at the
      University of Malta. Data were collected by the NEO Five-Factor Inventory (Costa
      and McCrae, 1992a) in 2006. While acknowledging that this study limits
      generalisation of the findings such as, collection of data in the third year of
      the course, following an attrition rate of 47% (Diploma) and 23% (BSc) since the
      start of the course programme, the findings presented in part two shed light on
      the nature of personality traits of students who are attracted towards the
      nursing profession.

PMID- 22585021
TI  - Adults posing as children and gender dysmorphism: a case study.
AB  - This article explores a case of a female who presented herself as a male to an
      accident and emergency department, where her father collaborated with her. This
      case is explored from many perspectives. Safeguarding is considered from both the
      welfare of this young person, and from their desire to be admitted to a
      children's ward. Gender dysmorphisim is becoming increasingly more recognised in
      the UK, yet it remains rare and is considered here as many nurses will not have
      encountered it. In a challenging situation, as presented here, the role of the
      nurse remains unchanged and a family-centred care approach must continue to be
      practised, while ensuring the care environment is safe for all concerned.

PMID- 22585022
TI  - Chrysalis to butterfly: improving access to psychological therapies.

PMID- 22585023
TI  - Care homes: quality and patient safety challenges.

PMID- 22585024
TI  - Nurses and mental health: breaking down the barriers.

PMID- 22585025
TI  - Simulated practice learning  in a preregistration programme.
AB  - Following the publication of the Nursing and Midwifery Council's (NMC) (2007)
      Simulation of Practice Learning Project, simulated practice learning
      opportunities are now to be incorporated into preregistration undergraduate
      nursing programmes across the UK. Since 2008, the Faculty of Health and Life
      Sciences at Oxford Brookes University has incorporated simulated practice
      learning into their curriculum to contribute towards students' 2300 direct
      clinical care hours. This paper presents the findings of an evaluation project
      that was conducted by academic staff within the faculty to ensure that they could
      continue to meet the principles set out by the NMC for auditing simulated
      learning environments used by higher education institutes (HEIs), and to meet the
      Essential Skills Clusters (NMC, 2010a) for registration as part of the quality
      assurance processes. The evaluation took place over 2 days, with a total of 52
      participants, including practice partners, mentors, practice educators, academic
      staff and students from all four branches of nursing (adult, mental health,
      learning disability and children). Results indicated that the support of direct
      care hours through simulated practice learning can permit students to practice
      essential clinical skills in a designated clinical skills suite. These learning
      experiences can also offer positive outcomes and the opportunities to maintain
      partnership for students, placement partners, and mentors.

PMID- 22585026
TI  - Professional development:  from staff nurse to nurse consultant.  Part 7:
      application forms.

PMID- 22585027
TI  - Can doctors lawfully kill competent patients who want to die?
AB  - This article explores the case of Nicklinson v Ministry of Justice (2012), in
      which a man with locked-in syndrome sought leave to challenge the current law
      concerning euthanasia. This is a preliminary hearing outlining the legal
      arguments being brought to trial; however, the article suggests that the
      significance of this case is likely to be considerable. It will require the
      English courts to consider the application of the doctrine of necessity and the
      application of the Human Rights Act in the context of active euthanasia by
      clinicians, rather than simply assisted suicide.

PMID- 22585028
TI  - Higher education 'category mistakes': are they relevant?

PMID- 22585029
TI  - A view from the North: do older people need more nurses?

PMID- 22585030
TI  - Red blood cell transfusion in neurosurgery.
AB  - BACKGROUND: The necessity of red blood cell (RBC) transfusions in neurosurgical
      procedures is under debate. Although detailed recommendations exist for many
      other surgical disciplines, there are very limited data on the probability of
      transfusions during neurosurgical procedures. METHODS: Three-thousand and twenty
      six consecutive adult patients undergoing neurosurgical procedures at Saarland
      University Hospital from December 2006 to June 2008 were retrospectively analyzed
      for administration of RBCs. The patients were grouped into 11 main diagnostic
      categories for analysis. The transfusion probability and cross-match to
      transfusion ratio (C/T ratio) were calculated. RESULTS: Overall, the transfusion
      probability for neurosurgical procedures was 1.7 % (52/3,026). The probability
      was 6.5 % for acute subdural hematoma (7/108), 6.2 % for spinal tumors (5/80),
      4.6 % for intracerebral hemorrhage (ICH, 4/98), 2.8 % for abscess (3/108), 2.4 %
      for traumatic brain injury (4/162), 2.3 % for cerebral ischemia (1/44), 1.9 % for
      subarachnoid hemorrhage (SAH) /aneurysms (4/206), 1.4 % for brain tumors
      (10/718), 0.8 % for hydrocephalus (2/196), 0.4 % for degenerative diseases of the
      spine (5/1290), including 3.6 % (3/82) for posterior lumbar interbody fusion
      (PLIF) and 0 % for epidural hematoma (0/15). The transfusion probabilities for
      clipping and coiling of SAH were 2.9 % (2/68) and 1.7 % (2/120) respectively.
      CONCLUSIONS: The probability of blood transfusion during neurosurgical procedures
      is well below the 10 % level which is generally defined as the limit for
      preoperative appropriation of RBCs. Patients with spinal tumors, acute subdural
      hematomas or ICH, i.e., patients undergoing large decompressive procedures of
      bone or soft tissue, had a higher probability of transfusion.

PMID- 22585031
TI  - The intra-operative use of blood products in neurosurgical operations.

PMID- 22585032
TI  - Reduction and oxidation of SrCoO2.5 thin films at low temperatures.
AB  - Brownmillerite SrCoO(2.5) (010) thin films synthesized by pulsed laser deposition
      became amorphous when reduced at low temperatures by CaH(2), indicating that the
      infinite-layer structure with the square planar Co(2+)O(4) configuration is
      unstable. Ferromagnetic and conducting perovskite SrCoO(3) epitaxial thin films,
      on the other hand, were obtained topotactically at room temperature by oxidation
      with NaClO.

PMID- 22585033
TI  - Nocturnal enuresis antecedent is common in adolescents with migraine.
AB  - BACKGROUND: Migraine and nocturnal enuresis are highly prevalent disorders with
      striking similarities. Both have unknown pathophysiology and are considered
      multifactorial, with neurobiological, genetic, and behavioral aspects involved.
      Interestingly, the same neurological structures thought to be involved in the
      pathogenesis of migraine are also thought to be involved in nocturnal enuresis.
      Few studies, however, have addressed these conditions as related. The aim of this
      study was to evaluate the antecedent of nocturnal enuresis in a large consecutive
      series of adolescents with migraine as compared to controls. METHODS: A total of
      151 subjects were evaluated; 50 had episodic migraine, 50 had chronic migraine,
      and 51 were control subjects. All patients were submitted to a detailed
      questionnaire addressing epidemiological and clinical aspects. RESULTS: There was
      a strong correlation between the clinical history of nocturnal enuresis and the
      diagnosis of migraine. CONCLUSION: Our study showed that nocturnal enuresis is a
      precursor of migraine and a migraine comorbid condition. These results support a
      pathophysiological linkage between the two conditions.

PMID- 22585034
TI  - The acute effects of exercise on cigarette cravings, withdrawal symptoms, affect,
      and smoking behaviour: systematic review update and meta-analysis.
AB  - RATIONALE: Smoking cessation is associated with cigarette cravings and tobacco
      withdrawal symptoms (TWS), and exercise appears to ameliorate many of these
      negative effects. A number of studies have examined the relationships between
      exercise, cigarette cravings, and TWS. OBJECTIVES: The objectives of this study
      were (a) to review and update the literature examining the effects of short bouts
      of exercise on cigarette cravings, TWS, affect, and smoking behaviour and (b) to
      conduct meta-analyses of the effect of exercise on cigarette cravings. METHODS: A
      systematic review of all studies published between January 2006 and June 2011 was
      conducted. RESULTS: Fifteen new studies were identified, 12 of which found a
      positive effect of exercise on cigarette cravings. The magnitude of statistically
      significant effect sizes for 'desire to smoke' and 'strength of desire to smoke'
      ranged from 0.4 to 1.98 in favour of exercise compared to passive control
      conditions, and peaked either during or soon after treatment. Effects were found
      up to 30 min post-exercise. Cigarette cravings were reduced following exercise
      with a wide range of intensities from isometric exercise and yoga to activity as
      high as 80-85 % heart rate reserve. Meta-analyses revealed weighted mean
      differences of -1.90 and -2.41 in 'desire to smoke' and 'strength of desire to
      smoke' outcomes, respectively. Measures of TWS and negative affect were reduced
      following light-moderate intensity exercise, but increased during vigorous
      exercise. CONCLUSIONS: Exercise can have a positive effect on cigarette cravings
      and TWS. However, the most effective exercise intensity to reduce cravings and
      the underlying mechanisms associated with this effect remain unclear.

PMID- 22585036
TI  - Retraction note to: Neonatal umbilical myiasis with sepsis.

PMID- 22585035
TI  - Two circulating neutrophil populations in acute inflammation in mice.
AB  - OBJECTIVE AND DESIGN: Recent studies indicate that neutrophils are heterogeneous
      and may have an immunosuppressive role in addition to their well-known phagocytic
      and bactericidal function. This study examined neutrophil subpopulations in the
      circulation, peritoneum, spleen and bone marrow from mice at various time points
      after induction of acute inflammation. MATERIAL, TREATMENT AND METHODS: Female
      C57BL/6 mice were injected intraperitoneally with lipopolysaccharide (LPS).
      Blood, peritoneal, spleen and bone marrow cells were collected and counted and
      expression of surface molecules and chemokine receptors analyzed with flow
      cytometry. Chemokine and cytokine concentrations in serum and peritoneal fluid
      were determined by ELISA. RESULTS: Neutrophil numbers in the circulation
      decreased following administration of LPS but reached similar numbers to those
      prior to inflammation at 8 h. At that time point, two distinct neutrophil
      populations were present in the circulation. These two neutrophil populations
      differed in size, granularity and expression of CD11b and Ly6G. Few neutrophils
      were recruited into the peritoneum until 24 h after administration of LPS at a
      time when the neutrophils in the circulation had increased their expression of
      the chemokine receptor CXCR2. CONCLUSIONS: Induction of acute inflammation leads
      to the appearance of two circulating neutrophil subpopulations, which may differ
      in their activation state and function.

PMID- 22585037
TI  - Gsdma3 is a new factor needed for TNF-alpha-mediated apoptosis signal pathway in
      mouse skin keratinocytes.
AB  - Gsdma3, a newly found gene, is expressed restrictedly in mouse skin keratinocytes
      and gastrointestinal tract. But until now, there is little information on the
      regulation and the function of Gsdma3 in skin keratinocytes. In our previous
      study, we found that Gsdma3 mutation resulted in a decrease in catagen-associated
      apoptosis of hair follicle keratinocytes. Apoptosis of skin keratinocytes is
      strictly regulated by a series of signal pathways, among of which, tumor necrosis
      factor (TNF)-alpha-induced signal pathway has been extensively studied. To
      further investigate the role and the pathway of Gsdma3 involved in skin
      keratinocyte apoptosis, using immunofluorescence, RT-PCR, western blot and TUNEL
      analysis, we showed here that accompanying TNF-alpha-induced apoptosis and
      Caspase-3 expression in mouse skin keratinocytes in vivo and in vitro, Gsdma3
      expression was significantly upregulated. After Gsdma3 gene mutation, TNF-alpha
      induced apoptosis and Caspase-3 expression in skin keratinocytes were reduced.
      The injection of Gsdma3 expression plasmid could directly enhance the apoptosis
      and Caspase-3 expression in skin keratinocytes. These results, taken together,
      indicated that in mouse skin keratinocytes, Gsdma3 expression could be regulated
      by TNF-alpha. Gsdma3 was not only involved in but also necessary for the TNF
      alpha-induced apoptosis pathway by directly enhancing the Caspase3 expression as
      well as the apoptosis induction.

PMID- 22585038
TI  - Detection of caveolin-3/caveolin-1/P2X7R complexes in mice atrial cardiomyocytes
      in vivo and in vitro.
AB  - Caveolae and caveolins, structural components of caveolae, are associated with
      specific ion channels in cardiac myocytes. We have previously shown that P2X
      purinoceptor 7 (P2X7R), a ligand-gated ion channel, is increased in atrial
      cardiomyocytes of caveolin-1 knockout mice; however, the specific biochemical
      relationship of P2X7R with caveolins in the heart is not clear. The aim of this
      work was to study the presence of the P2X7R in atrial cardiomyocytes and its
      biochemical relationship to caveolin-1 and caveolin-3. Caveolin isoforms and
      P2X7R were predominantly localized in buoyant membrane fractions (lipid
      rafts/caveolae) prepared from hearts using detergent-free sucrose gradient
      centrifugation. Caveolin-1 knockout mice showed normal distribution of caveolin-3
      and P2X7R to buoyant membranes indicating the importance of caveolin-3 to
      formation of caveolae. Using clear native-PAGE, we showed that caveolin-1, -3 and
      P2X7R contribute to the same protein complex in the membranes of murine
      cardiomyocytes and in the immortal cardiomyocyte cell line HL-1. Western blot
      analysis revealed increased caveolin-1 and -3 proteins in tissue homogenates of
      P2X7R knockout mice. Finally, tissue homogenates of atrial tissues from caveolin
      3 knockout mice showed elevated mRNA for P2X7R in atria. The colocalization of
      caveolins with P2X7R in a biochemical complex and compensated upregulation of
      P2X7R or caveolins in the absence of any component of the complex suggests P2X7R
      and caveolins may serve an important regulatory control point for disease
      pathology in the heart.

PMID- 22585039
TI  - Nuage proteins: their localization in subcellular structures of spermatogenic
      cells as revealed by immunoelectron microscopy.
AB  - Chromatoid body (CB) was identified as granules stained by basic dye 130 years
      ago and called by various names. Electron microscopy revealed that the CB
      belonged to nuage (cloud in French) specific for germ cells. We described the
      localization of several proteins, including RNA helicases, in the nuage
      compartments classified into six types and in several spermatogenic cell-specific
      structures. All the proteins examined were detected in the nuage, including the
      CB with different staining intensities. Several proteins were localized to non
      nuage structures, suggesting that these nuage proteins structures are related to
      nuage function.

PMID- 22585041
TI  - Obesity: comBATting obesity.

PMID- 22585042
TI  - Effects of potential environmental interferents on kinesin-powered molecular
      shuttles.
AB  - Biomolecular motor-powered active transport represents an alternate means for
      analyte processing in nanoscale biosensors and bioanalytical devices. For
      example, a prototype "smart dust" biosensor has recently been reported in which
      the motor protein kinesin processes antibody-functionalized microtubules (MTs) to
      capture and separate optically tagged protein analytes. A potential limitation of
      this technology, however, involves the inhibition of transport function by
      interfering compounds that may be present in raw samples. Here we characterized
      the response of kinesin-MT transport to a range of potential interferents
      including solvents, acids, oxidizers, and environmental contaminants. The results
      of kinesin motility assays suggest that, among the tested interferents, only
      acetic acid and sodium hypochlorite adversely affected MT transport, primarily
      due to depolymerization of MT filaments. While negative effects were not observed
      for the remaining compounds tested, enhancement in motility was observed in the
      presence of acetone, antifreeze, and organic matter. Overall, the data suggest
      that kinesin-MT transport is resilient against a variety of common interferents,
      but primarily susceptible to failure due to significant changes in pH or the
      presence of an oxidizer.

PMID- 22585040
TI  - Fatty acid-binding protein 4 (FABP4) and FABP5 modulate cytokine production in
      the mouse thymic epithelial cells.
AB  - Thymic stromal cells, including cortical thymic epithelial cells (cTEC) produce
      many humoral factors, such as cytokines and eicosanoids to modulate thymocyte
      homeostasis, thereby regulating the peripheral immune responses. In this study,
      we identified fatty acid-binding protein (FABP4), an intracellular fatty acid
      chaperone, in the mouse thymus, and examined its role in the control of cytokine
      production in comparison with FABP5. By immunofluorescent staining, FABP4(+)
      cells enclosing the thymocytes were scattered throughout the thymic cortex with a
      spatial difference from the FABP5(+) cell that were distributed widely throughout
      the cTEC. The FABP4(+) cells were immunopositive for MHC class II, NLDC145 and
      cytokeratin 8, and were identified as part of cTEC. The FABP4(+) cells were
      identified as thymic nurse cells (TNC), a subpopulation of cTEC, by their active
      phagocytosis of apoptotic thymocytes. Furthermore, FABP4 expression was confirmed
      in the isolated TNC at the gene and protein levels. To explore the function of
      FABP in TNC, TSt-4/DLL1 cells stably expressing either FABP4 or FABP5 were
      established and the gene expressions of various cytokines were examined. The gene
      expression of interleukin (IL)-7 and IL-18 was increased both in FABP4 and FABP5
      over-expressing cells compared with controls, and moreover, the increase in their
      expressions by adding of stearic acids was significantly enhanced in the FABP4
      over-expressing cells. These data suggest that both FABPs are involved in the
      maintenance of T lymphocyte homeostasis through the modulation of cytokine
      production, which is possibly regulated by cellular fatty acid-mediated signaling
      in TEC, including TNC.

PMID- 22585043
TI  - Cytoskeleton keratin regulation of FasR signaling through modulation of
      actin/ezrin interplay at lipid rafts in hepatocytes.
AB  - FasR stimulation by Fas ligand leads to rapid formation of FasR microaggregates,
      which become signaling protein oligomerization transduction structures (SPOTS),
      through interactions with actin and ezrin, a structural step that triggers death
      inducing signaling complex formation, in association with procaspase-8
      activation. In some cells, designated as type I, caspase 8 directly activates
      effector caspases, whereas in others, known as type II, the caspase-mediated
      death signaling is amplified through mitochondria. Keratins are the intermediate
      filament (IF) proteins of epithelial cells, expressed as pairs in a
      lineage/differentiation manner. Hepatocyte IFs are made solely of keratins 8/18
      (K8/K18), the hallmark of all simple epithelia. We have shown recently that in
      comparison to type II wild-type (WT) mouse hepatocytes, the absence of K8/K18 IFs
      in K8-null hepatocytes leads to more efficient FasR-mediated apoptosis, in link
      with a type II/type I-like switch in FasR-death signaling. Here, we demonstrate
      that the apoptotic process occurring in type I-like K8-null hepatocytes is
      associated with accelerated SPOTS elaboration at surface membrane, along with
      manifestation of FasR cap formation and internalization. In addition, the lipid
      raft organization is altered in K8-null hepatocytes. While lipid raft inhibition
      impairs SPOTS formation in both WT and K8-null hepatocytes, the absence of K8/K18
      IFs in the latter sensitizes SPOTS to actin de-polymerization, and perturbs ezrin
      compartmentalization. Overall, the results indicate that the K8/K18 IF loss in
      hepatocytes alters the initial FasR activation steps through perturbation of
      ezrin/actin interplay and lipid raft organization, which leads to a type II/type
      I switch in FasR-death signaling.

PMID- 22585046
TI  - Phylogenetic analysis of rabbit hemorrhagic disease virus in China and the
      antigenic variation of new strains.
AB  - This study aimed to investigate rabbit hemorrhagic disease virus (RHDV) in China.
      VP60 sequences of five RHDVs collected by our team, as well as those of 16 other
      published Chinese RHDV strains, were analyzed. Polygenic analysis using MEGA 4
      software showed that 20 of the 21 Chinese strains could be clustered in the RHDVa
      subgroup, and WX/China/1984 was different from them. The Chinese RHDV strains
      were further classified into four subgroups, CH1 to CH4. Subgroup CH1,
      represented by the WX/China/1984 strain, was not prevalent in China after the
      first RHDV epidemic strain was reported. The CH2, CH3, and CH4 subgroups were far
      different from the CH1 subgroup, formed three separate clusters, and were
      distributed according to the time the strains were collected. Recently collected
      strains formed a new subgroup (CH4), represented by new RHDV varieties identified
      by challenging immunized rabbits and by comparison of genomic sequences. The
      present work is the first comprehensive analysis of Chinese RHDV and reveals a
      new RHDV variation that should be carefully monitored.

PMID- 22585045
TI  - Antigen capture ELISA system for henipaviruses using polyclonal antibodies
      obtained by DNA immunization.
AB  - A novel antigen-capture sandwich ELISA system targeting the glycoproteins of the
      henipaviruses Nipah virus (NiV) and Hendra virus (HeV) was developed. Utilizing
      purified polyclonal antibodies derived from NiV glycoprotein-encoding DNA
      immunized rabbits, we established a system that can detect the native antigenic
      structures of the henipavirus surface glycoproteins using simplified and
      inexpensive methods. The lowest detection limit against live viruses was achieved
      for NiV Bangladesh strain, 2.5 * 10(4) TCID(50). Considering the recent emergence
      of genetic variants of henipaviruses and the resultant problems that arise for
      PCR-based detection, this system could serve as an alternative rapid diagnostic
      and detection assay.

PMID- 22585044
TI  - Current epidemiology of diabetic retinopathy and diabetic macular edema.
AB  - With increasing global prevalence of diabetes, diabetic retinopathy (DR) is set
      to be the principle cause of vision impairment in many countries. DR affects a
      third of people with diabetes and the prevalence increases with duration of
      diabetes, hyperglycemia, and hypertension-the major risk factors for the onset
      and progression of DR. There are now increasing data on the epidemiology of
      diabetic macular edema (DME), an advanced complication of DR, with studies
      suggesting DME may affect up to 7 % of people with diabetes. The risk factors for
      DME are largely similar to DR, but dyslipidemia appears to play a more
      significant role. Early detection of DR and DME through screening programs and
      appropriate referral for therapy is important to preserve vision in individuals
      with diabetes. Future research is necessary to better understand the potential
      role of other risk factors such as apolipoproteins and genetic predisposition to
      shape public health programs.

PMID- 22585048
TI  - Computerised cognitive behavioural therapy for insomnia: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Computerised cognitive behavioural therapy (CCBT) is an innovative
      mode of delivering services to patients with psychological disorders. The present
      paper uses a meta-analysis to systematically review and evaluate the
      effectiveness of CCBT for insomnia (CCBT-I). METHOD: A comprehensive search was
      conducted on 7 databases including MEDLINE, PsycINFO, EMBASE, CINAHL, Cochrane
      Library, Social Sciences Citation Index and PubMed (up to March 2011). Search
      terms covered 3 concepts: (1) [internet, web, online, computer-aided, computer
      assisted, computer-guided, computerized OR computerised] AND (2) [CBT, cognitive
      therapy, behavio(u)ral therapy OR behavio(u)r therapy] AND (3) [insomnia, sleep
      disorders OR sleeping problem]. RESULTS: 533 potentially relevant papers were
      identified, and 6 randomised controlled trials (RCTs) that met the selection
      criteria were included in the review and analysis. Two RCTs were done by the same
      group of investigators (Ritterband and colleagues) using the same internet
      programmes. Post-treatment mean differences between groups showed that the
      effects of CCBT-I on sleep quality, sleep efficiency, the number of awakenings,
      sleep onset latency and the Insomnia Severity Index were significant, ranging
      from small to large effect sizes. However, effects on wake time after sleep
      onset, total sleep time and time in bed were non-significant. On average, the
      number needed to treat was 3.59. The treatment adherence rate for CCBT-I was high
      (78%). CONCLUSION: The results lend support to CCBT as a mildly to moderately
      effective self-help therapy in the short run for insomnia. CCBT-I can be an
      acceptable form of low-intensity treatment in the stepped care model for
      insomnia.

PMID- 22585047
TI  - Molecular prevalence of bovine noroviruses and neboviruses detected in central
      eastern Tunisia.
AB  - Two genetically distinct bovine enteric caliciviruses are known: noroviruses of
      genogroup III (NoVsGIII), which are genetically related to human noroviruses, and
      neboviruses, which represent a new calicivirus genus. To investigate the presence
      of NoVsGIII and nebovirus strains in diarrheic calves in Tunisia, a total of 169
      faecal specimens were collected from January 2006 to October 2010 from different
      cattle herds located in the central-east regions. RT-PCRs and sequencing were
      carried out using primers targeting the 3' end of the polymerase gene of NoVsGIII
      and neboviruses. This study revealed that NoVsGIII and nebovirus are endemic in
      diarrheic calves in Tunisia. NoVsGIII infections, all with genotype 2, had an
      apparent molecular prevalence of 16.6 % and were more frequent than nebovirus
      infections. NoVsGIII infections showed clear seasonality, with a peak in winter.
      Nebovirus infections, with a prevalence of 3.0 %, were all related to the
      reference strain Bo/Nebraska/80/US.

PMID- 22585049
TI  - Berger C. Mayne (1920-2011): a friend and his contributions to photosynthesis
      research.
AB  - We provide here insights on the life and work of Berger C. Mayne (1920-2011). We
      remember and honor Berger, whose study of photosynthesis began with the most
      basic processes of intersystem electron transport and oxygen evolution, continued
      with application of fluorescence techniques to the study of photophosphorylation
      and the unique features of photosystems in specialized cells, and concluded with
      collaborative study of photosynthesis in certain nitrogen fixing symbioses.
      Berger loved the outdoors and was dedicated to preserving the environment and to
      social justice, and was a wonderful friend.

PMID- 22585050
TI  - Increased plasma levels of high mobility group box 1 in patients with acute liver
      failure.
AB  - BACKGROUND: High-mobility group box 1 (HMGB1) is a monocyte-derived late-acting
      inflammatory mediator, which is released in conditions such as shock, tissue
      injury and endotoxin-induced lethality. In this study, we determined the plasma
      and hepatic tissue levels of HMGB1 in patients with acute liver failure (ALF).
      PATIENTS AND METHODS: We determined the plasma levels of HMGB1 and aspartate
      aminotransferase (AST) in 7 healthy volunteers (HVs), 40 patients with liver
      cirrhosis (LC), 37 patients with chronic hepatitis (CH), 18 patients with severe
      acute hepatitis (AH), and 14 patients with fulminant hepatitis (FH). The 14
      patients with FH were divided into two subgroups depending upon the history of
      plasma exchange (PE) before their plasma sample collection. The hepatic levels of
      HMGB1 were measured in tissue samples from 3 patients with FH who underwent
      living-donor liver transplantation and from 3 healthy living donors. Hepatic
      tissue samples were also subjected to immunohistochemical examination for HMGB1.
      RESULTS: The plasma levels of HMGB1 (ng/ml) were higher in patients with liver
      diseases, especially in FH patients with no history of PE, than in HVs (0.3 +/-
      0.3 in HVs, 4.0 +/- 2.0 in LC, 5.2 +/- 2.6 in CH, 8.6 +/- 4.8 in severe AH, 7.8
      +/- 2.7 in FH with a history of PE, and 12.5 +/- 2.6 in FH with no history of PE,
      p < 0.05 in each comparison). There was a strong and statistically significant
      relationship between the mean plasma HMGB1 level and the logarithm of the mean
      AST level (R = 0.900, p < 0.05). The hepatic tissue levels of HMGB1 (ng/mg tissue
      protein) were lower in patients with FH than in healthy donors (539 +/- 116 in FH
      vs. 874 +/- 81 in healthy donors, p < 0.05). Immunohistochemical staining for
      HMGB1 was strong and clear in the nuclei of hepatocytes in liver sections from
      healthy donors, but little staining in either nuclei or cytoplasm was evident in
      specimens from patients with FH. CONCLUSION: We confirmed that plasma HMGB1
      levels were increased in patients with ALF. Based on a comparison between HMGB1
      contents in normal and ALF livers, it is very likely that HMGB1 is released from
      injured liver tissue.

PMID- 22585052
TI  - Synthesis and characterization of novel titanium complexes bearing [ONX]-type
      beta-enaminoketonato ligands and their application to ethylene
      (co)polymerization.
AB  - A series of novel titanium complexes bearing tridentate beta-enaminoketonato
      chelating ligands of type, [R(2)NC(CF(3))C(H)CR(1)O]TiCl(3) (2a: R(1) = Ph, R(2)
      = -C(6)H(4)OMe(o); 2b: R(1) = Ph, R(2) = -C(9)H(6)N; 2c: R(1) = Ph, R(2) = 
      C(6)H(4)SMe(o); 2d: R(1) = Ph, R(2) = -C(6)H(4)SPh(o); 2e: R(1) = (t)Bu, R(2) = 
      C(6)H(4)SPh(o)) and [R(2)NC(R(1))C(H)C(CF(3))O]TiCl(3) (2f: R(1) = Ph, R(2) = 
      C(6)H(4)PPh(2)(o)) were prepared from TiCl(4) by treating with one equiv of
      deprotonated ligands in toluene. The reaction of 1a with equivalent of TiCl(4) in
      THF afforded another complex, C(6)H(4)OMeNC(CF(3))C(H)CPhO]TiCl(3)(thf) (3a), in
      addition to formation of the dichloride complex 4a,
      [C(6)H(4)(OMe)NC(CF(3))C(H)CPhO](2)TiCl(2). After deprotonation by alkali-metal
      hydride at -78  degrees C in diethyl ether, ligand 1a could react with 0.5 equiv
      of TiCl(4) to form the exclusive and clean dichloride complex 4a in high yield.
      These complexes were identified by NMR and mass spectra as well as elemental
      analyses. X-ray diffraction studies on these new trichloride complexes revealed a
      distorted octahedral coordination of the central metal with three chlorine atoms
      in a mer disposition. Dichloride complex 4a also adopted a distorted octahedral
      geometry around the titanium center. Two chlorine atoms are situated in the cis
      position, as seen in the bond angles for Cl(1)-Ti-Cl(2) (92.64(7) degrees ). The
      O atom on the heterocyclic group was not coordinated with Ti. When activated by
      modified methylaluminoxane (MMAO), complexes 2a-e exhibited moderate to high
      activity towards ethylene (co)polymerization, giving relatively high molecular
      weight polymers with unimodal molecular weight distribution.

PMID- 22585051
TI  - Analysis of the Th1/Th2 reaction in the immune response induced by EV71
      inactivated vaccine in neonatal rhesus monkeys.
AB  - Although clinical trials for the enterovirus type 71 (EV71) inactivated vaccine
      have been progressing, the potential mechanism of EV71 infection and its
      associated pathogenesis are not well-characterized in terms of comprehensive
      analysis of the induced immune response, which is generally recognized as an
      important indicator of the safety of vaccines. To investigate the Th1/Th2
      response following viral challenge in neonatal rhesus monkeys immunized with
      different doses of EV71 inactivated vaccines, the variety of different Th1 and
      Th2 cytokines in the organs or tissues of the monkeys were identified. The
      results suggest that depending on the viral challenge, the Th1/Th2 reaction
      induced by different doses of EV71 inactivated vaccine varies. More specifically,
      there is an enhanced immune response in 80EU- and 1280EU-immunized monkeys,
      whereas 320EU immunization induces a mild response. Although there is no direct
      impact on the variation in immune protection induced by the vaccine, the Th1
      reaction functions in T-cell cytotoxicity, which will aid further investigation
      of the pathogenic characteristics of small pathological changes in the central
      nerves system (CNS) likely induced by the Th1 response.

PMID- 22585053
TI  - Fluorescence recovery after photobleaching reveals the biochemistry of
      nucleocytoplasmic exchange.
AB  - Fluorescence recovery after photobleaching (FRAP) can help unveil subtle
      dynamical and biochemical properties of intracellular components. A peculiar
      aspect of this method is that it is based on the change of optical properties
      only, whereas dynamics and biochemistry of the molecules of interest are not
      perturbed. This makes FRAP particularly suitable for the study of protein
      translocation, e.g., between nucleus and cytoplasm. Here we present a
      comprehensive theoretical treatment of FRAP applied to protein nucleocytoplasmic
      translocation by passive diffusion and/or energy-driven processes across the
      nuclear envelope. Our mathematical model is validated by experimental FRAP
      studies with functionalized fluorescent protein chimeras. Using this approach we
      demonstrate that molecular crowding at the nuclear pore does not hamper passive
      diffusion and calculate the dimension of the nuclear pore size (5.33 nm).
      Additionally, our FRAP analysis reveals the biochemical parameters (maximum
      translocation rate and dissociation constant of the transport complex in
      cytoplasm) associated with the active import of a prototypical nuclear
      localization sequence (NLS of SV40) and related mutants. We demonstrate that
      transportin binding and active import into the nucleus are independent processes
      that can be separately modulated. The present results are discussed in light of
      their potential to help in engineering sequences for intracellular targeted
      delivery of sensors and/or therapeutic compounds. Finally, the limits of validity
      of our mathematical model are addressed.

PMID- 22585054
TI  - Applicability of multisyringe chromatography coupled to on-line solid-phase
      extraction to the simultaneous determination of dicamba, 2,4-D, and atrazine.
AB  - Simultaneous determination of three herbicides (dicamba, 2,4-D, and atrazine) has
      been achieved by on-line solid-phase extraction (SPE) coupled to multisyringe
      chromatography (MSC) with UV detection. The preconcentration conditions were
      optimized; a preconcentration flow rate of 0.5 mL min(-1) and elution at 0.8 mL
      min(-1) were the optimum conditions. A C(18) (8 mm i.d.) membrane extraction disk
      conditioned with 0.3 mol L(-1) HCl in 0.5% MeOH was used. A 3-mL sample was
      preconcentrated, then eluted with 0.43 mL 40:60 water-MeOH. A C(18) monolithic
      column (25 mm * 4.6 mm) was used for chromatographic separation. Separation of
      the three compounds was achieved in 10 min by use of 0.01% aqueous acetic acid
      MeOH (60:40) as mobile phase at a flow rate of 0.8 mL min(-1). The limits of
      detection (LOD) were 13, 57, and 22 MUg L(-1) for dicamba, 2,4-D, and atrazine,
      respectively. The sampling frequency was three analyses per hour, and each
      analysis consumed only 7.3 mL solvent. The method was applied to spiked water
      samples, and recovery between 85 and 112% was obtained. Recovery was
      significantly better than in the conventional HPLC-UV method. These results
      indicated the reliability and accuracy of this flow-based method. This is the
      first time this family of herbicides has been simultaneously analyzed by on-line
      SPE-MSC using a monolithic column.

PMID- 22585055
TI  - Enantiomeric separations of chiral polychlorinated biphenyls on three
      polysaccharide-type chiral stationary phases by supercritical fluid
      chromatography.
AB  - Enantiomeric separations of 18 chiral polychlorinated biphenyls (PCBs) were
      investigated on three polysaccharide-type chiral stationary phases (CSPs; Sino
      Chiral OJ, Chiralpak IB, and Chiralcel OD) by supercritical fluid chromatography
      (SFC). With these commonly used polysaccharide CSPs, 17 PCBs except PCB 135 (R(S)
      = 0.81) were well resolved (R(S) > 1.5) under appropriate mobile phases and
      temperatures. Using Sino-Chiral OJ, 14 PCBs could be baseline-separated, while
      only one and nine PCBs could be completely separated using Chiralpak IB and
      Chiralcel OD, respectively. The influence of column temperature was studied for
      the optimization of resolution, as well as for the type and percentage of organic
      modifier in the mobile phase. The resolution decreased as the temperature
      increased in the range of 26-40  degrees C in which the enantiomeric separations
      were an enthalpy-driven process. The addition of modifiers in the mobile phase
      decreased the resolution of the PCB enantiomers, but it clearly shortened their
      retention time. These separation results indicate that SFC is a promising
      chromatographic technique for chiral separation and enantiopure standard
      preparation.

PMID- 22585056
TI  - Rapid reagentless quantification of alginate biosynthesis in Pseudomonas
      fluorescens bacteria mutants using FT-IR spectroscopy coupled to multivariate
      partial least squares regression.
AB  - Alginate is an important medical and commercial product and currently is isolated
      from seaweeds. Certain microorganisms also produce alginate and these polymers
      have the potential to replace seaweed alginates in some applications, mainly
      because such production will allow much better and more reproducible control of
      critical qualitative polymer properties. The research conducted here presents the
      development of a new approach to this problem by analysing a transposon insertion
      mutant library constructed in an alginate-producing derivative of the Pseudomonas
      fluorescens strain SBW25. The procedure is based on the non-destructive and
      reagent-free method of Fourier transform infrared (FT-IR) spectroscopy which is
      used to generate a complex biochemical infrared fingerprint of the medium after
      bacterial growth. First, we investigate the potential differences caused by the
      growth media fructose and glycerol on the bacterial phenotype and alginate
      synthesis in 193 selected P. fluorescens mutants and show that clear phenotypic
      differences are observed in the infrared fingerprints. In order to quantify the
      level of the alginate we also report the construction and interpretation of
      multivariate partial least squares regression models which were able to quantify
      alginate levels successfully with typical normalized root-mean-square error in
      predictions of only approximately 14%. We have demonstrated that this high
      throughput approach can be implemented in alginate screens and we believe that
      this FT-IR spectroscopic methodology, when combined with the most appropriate
      chemometrics, could easily be modified for the quantification of other valuable
      microbial products and play a valuable screening role for synthetic biology.

PMID- 22585058
TI  - NOX enzymes as drug targets.

PMID- 22585059
TI  - NADPH oxidase inhibitors: a decade of discovery from Nox2ds to HTS.
AB  - NADPH oxidases (Nox) are established as major sources of reactive oxygen species
      (ROS). Over the past two decades, Nox-derived ROS have emerged as pivotal in the
      development of myriad diseases involving oxidative stress. In contrast, Nox are
      also involved in signaling mechanisms necessary for normal cell function. The
      study of these enzymes in physiological and pathophysiological conditions is made
      considerably more complex by the discovery of 7 isoforms: Nox1 through 5 as well
      as Duox1 and 2, each with its own specific cytosolic components, regulatory
      control mechanisms, subcellular localization and/or tissue distribution. A clear
      understanding of the role individual isoforms play in a given system is hindered
      by the lack of isoform-specific inhibitors. In animal models, knockdown or
      knockout methodologies are providing definitive answers to perplexing questions
      of the complex interplay of multiple Nox isoforms in cell and tissue signaling.
      However, the complex structures and interactions of these heteromeric isozymes
      predict pleiotropic actions of the Nox subunits and thus suppression of these
      proteins is almost certain to have untoward effects. Thus, as both therapies and
      pharmacological tools, molecule-based inhibitors continue to prove extremely
      useful and rational in design. Unfortunately, many of the available inhibitors
      have proven non-specific, falling into the category of scavengers or inhibitors
      of more than one source of ROS. Here, we will review some of the efforts that
      have been undertaken to develop specific inhibitors of NADPH oxidase over the
      past decade, from the peptidic inhibitor Nox2ds-tat to more recent small molecule
      inhibitors that have emerged from high-throughput screening campaigns.

PMID- 22585062
TI  - Gene regulation: Transcription factor clutch control.

PMID- 22585061
TI  - Risk for low back pain from different frequencies, load mass and trunk postures
      of lifting and carrying among female healthcare workers.
AB  - PURPOSE: To investigate the risk of developing non-chronic and chronic low back
      pain (LBP) from frequency, load mass and trunk postures of occupational lifting
      and carrying among female healthcare workers. METHODS: A total of 9,847 workers
      in eldercare answered a questionnaire about occupational lifting and carrying
      frequency (rarely, occasionally and frequently), load mass (low: 1-7 kg,
      moderate: 8-30 kg and heavy: >30 kg), trunk posture (upright or forward bent
      back), and days with LBP in 2005. The odds ratio (OR) for developing non-chronic
      (1-30 days the last 12 months) and chronic (>30 days the last 12 months) LBP
      reported in 2006 from these characteristics of occupational lifting and carrying
      was investigated with multi-adjusted logistic regressions among female healthcare
      workers without LBP in 2005 (n = 1,612). RESULTS: Frequently lifting and carrying
      low load mass with forward bent back doubled the risk for developing chronic LBP
      (OR: 2.14; 95 % CI: 1.02-4.50). Occasionally and frequently lifting or carrying
      of any load mass with upright back did not increase the risk for chronic LBP.
      Lifting and carrying did not increase the risk for non-chronic LBP. CONCLUSIONS:
      Preventive initiatives for LBP among healthcare workers ought to pay attention to
      frequent lifting and carrying of low load mass with forward bent back.

PMID- 22585064
TI  - Human genetics: Fruits of exome sequencing for autism.

PMID- 22585060
TI  - Depression and treatment response: dynamic interplay of signaling pathways and
      altered neural processes.
AB  - Since the 1960s, when the first tricyclic and monoamine oxidase inhibitor
      antidepressant drugs were introduced, most of the ensuing agents were designed to
      target similar brain pathways that elevate serotonin and/or norepinephrine
      signaling. Fifty years later, the main goal of the current depression research is
      to develop faster-acting, more effective therapeutic agents with fewer side
      effects, as currently available antidepressants are plagued by delayed
      therapeutic onset and low response rates. Clinical and basic science research
      studies have made significant progress towards deciphering the pathophysiological
      events within the brain involved in development, maintenance, and treatment of
      major depressive disorder. Imaging and postmortem brain studies in depressed
      human subjects, in combination with animal behavioral models of depression, have
      identified a number of different cellular events, intracellular signaling
      pathways, proteins, and target genes that are modulated by stress and are
      potentially vital mediators of antidepressant action. In this review, we focus on
      several neural mechanisms, primarily within the hippocampus and prefrontal
      cortex, which have recently been implicated in depression and treatment response.

PMID- 22585065
TI  - Mechanisms and consequences of widespread random monoallelic expression.
AB  - Although random monoallelic expression has been known for decades to affect genes
      on the X chromosome in female placental mammals, until a few years ago it was
      thought that there were few autosomal genes that were regulated in this manner.
      New tools for assaying gene expression genome-wide are now revealing that there
      are perhaps more genes that are subject to random monoallelic expression on
      mammalian autosomes than there are on the X chromosome and that these expression
      properties are achieved by diverse molecular mechanisms. This mode of expression
      has the potential to have an impact on natural selection and on the evolution of
      gene families.

PMID- 22585069
TI  - Elaine Fuchs. Interview by Hannah Stower.

PMID- 22585070
TI  - Stool transplants: ready for prime time?
AB  - Clostridium difficile infection (CDI) is a leading cause of antibiotic- and
      healthcare-related diarrhea. Predisposing factors for infection include
      antimicrobial use, exposure to healthcare settings, inflammatory bowel disease,
      chemotherapy and advanced age, although CDI is now seen in patients without
      traditional risk factors. The gut microbiome may hold clues to the
      pathophysiology of CDI and promoting a 'healthy' microbiome has become a focus
      for CDI therapy. Stool transplant or fecal microbiota transplantation has been
      shown to be safe and effective for management of recurrent CDI. We offer a
      protocol for stool transplantation.

PMID- 22585071
TI  - Learning disabilities:  meeting essential standards.

PMID- 22585072
TI  - Effective nurse-patient  communication in diabetes.

PMID- 22585073
TI  - Health promotion for people with intellectual disability and obesity.
AB  - Obesity is a significant health problem for people with intellectual disability,
      as they report a 59% higher rate of obesity as compared with those in the general
      population (Centres for Disease Control and Prevention, 2006). Causes are
      multifactorial and obesity leads to a higher risk of developing chronic
      conditions, such as diabetes and heart disease. While the risks of these
      conditions generally increase with age, people with an intellectual disability
      are at risk of developing them earlier owing to their higher levels of obesity.
      Client groups with mild intellectual disability residing in a group home or
      family home are at a higher risk of obesity than those in institutional care,
      mainly owing to increased independence and available choices. Healthcare services
      have predominantly focused on the primary disability rather than on prevention or
      reduction of secondary health conditions. As health promotion enables people to
      gain control over their lives, it is essential to address the health concern of
      obesity for people with intellectual disability. This article highlights the
      issues in health care faced by people with an intellectual disability and aspects
      that health professionals need to consider when engaging in health promotion for
      those who are obese.

PMID- 22585074
TI  - Meeting the health needs of older people with learning disabilities.
AB  - The increasing population of older people with learning disabilities may lead to
      higher demand for contact with registered nurses. To date, little research has
      been undertaken regarding the role of registered nurses in meeting the health and
      care needs of this client group. In this article, the author reports on the
      second stage of a three-stage research study that used six case studies to
      explore this issue. Implications for nursing were identified in areas such as
      health needs, record keeping, medication, advocacy, social aspects, ageing in
      place, percutaneous endoscopic gastrostomy (PEG) feeding, spirituality and end-of
      life care. The author concludes that registered nurses will need to continue to
      remain up to date to meet the complex needs of older individuals with learning
      disabilities.

PMID- 22585075
TI  - Nurses' role in managing  alcohol misuse among adolescents.
AB  - Over the past decade, there has been an increase in the amount of alcohol
      consumed by young people, aged 11-17 years, in the UK and Ireland, which has
      implications for all health professionals caring for adolescents. Alcohol misuse
      is increasingly common among adolescents and is a significant concern for
      families, communities and society. Health professionals need to be aware of the
      dangers involved with underage drinking, how to recognise the signs of alcohol
      misuse, and how to intervene appropriately. Over the past few years, there has
      been a noticeable increase in the number of adolescents presenting to emergency
      departments (EDs) owing to alcohol-related injuries. This increase means that all
      nurses and other health professionals are suitably placed to provide education
      and support to adolescents who are consuming excessive alcohol. Regular alcohol
      misuse can lead to adverse health outcomes, and therefore nurses need to take an
      active role in health promotion to ensure that adolescents are aware of the
      associated dangers. This article summarises the harmful effects of underage
      drinking, the influencing factors and outlines the current guidelines on alcohol
      misuse in young people. It discusses strategies that nurses can use in the ED
      setting, and all healthcare settings, to motivate adolescents to change health
      damaging behaviours.

PMID- 22585076
TI  - The role of anxiolytic premedication in reducing preoperative anxiety.
AB  - Prevention of preoperative anxiety with anxiolytic premedication is associated
      with improved preoperative outcomes in surgical patients. The objective of the
      authors' study was to evaluate the percentage of surgical patients that are
      prescribed premedication for preoperative anxiety before their anticipated
      surgical procedure. A prospective study was carried out by theatre nursing staff
      in the theatre reception bay of a university teaching hospital. A questionnaire
      was designed to record the number of patients that described symptoms consistent
      with preoperative anxiety. The number of patients that had been offered
      anxiolytic premedication for preoperative anxiety was also recorded. Consent was
      obtained from 115 consecutive surgical patients (male, n=52; female, n=63). Of
      these, 66% (n=76) reported anxiety before their surgical procedure (male: n=27,
      female: n=49). Premedication with a low-dose benzodiazepine was prescribed by an
      anaesthetist in 4% of cases (n=5). Patients that received premedication
      preoperatively reported effective relief of their anxiety symptoms This study
      demonstrates that preoperative patient anxiety is highly prevalent. The authors'
      findings suggest that premedication with anxiolytic pharmacological therapy may
      be an underused therapeutic resource for managing preoperative patient anxiety.

PMID- 22585078
TI  - Nursing leadership within the NHS:  an evolutionary perspective.
AB  - Effective leadership is crucial to the delivery of quality NHS care, particularly
      in the current economic climate. These are unprecedented times for the NHS; at no
      other time in its life has the need for leadership been greater. It is hard to
      define nursing leadership, with roles becoming increasingly complex. Although
      there has been much invested in leadership training, NHS guidance has suggested
      the service has only just begun to understand the importance of leadership. There
      is unparalleled change in the NHS; nurses are being asked to be innovators and
      entrepreneurs. In this article, the author considers what leadership is, and
      stresses the need for it to continue evolving to meet the changing demands of the
      NHS.

PMID- 22585077
TI  - Psychology in sports injury rehabilitation.
AB  - Using the case study of an 18-year-old track athlete with a chronic Achilles
      tendinopathy, this article identifies risk factors associated with training for
      major athletic events, such as the forthcoming Olympic Games, and presents
      evidence for adopting a multidisciplinary approach to the treatment and
      management of athletic injury, addressing the physical aspects of the injury, as
      well as the psychological needs of the athlete. The athlete's GP and practice
      nurse, as well as a podiatrist and sport psychologist, are all involved in
      providing an accurate clinical diagnosis, effective physical intervention, and
      psychological skills training to address emotional issues and encourage adherence
      to the rehabilitation programme. Nurses, in both secondary and primary care, can
      play a crucial role; in this case, the practice nurse recognised the adverse
      impact that the injury was having on the athlete's emotional wellbeing before
      making a referral to a trained sport psychologist.

PMID- 22585079
TI  - Escaping the ivory tower: emancipation of the modern clinical academic.

PMID- 22585080
TI  - The importance and urgency of addressing patient safety globally.

PMID- 22585081
TI  - Negotiating the unofficial hierarchy of placements.

PMID- 22585082
TI  - Professional development: from staff nurse to nurse consultant. Part 10:
      interviews.

PMID- 22585083
TI  - Boosting the public health  agenda through collaboration.

PMID- 22585084
TI  - XAS analysis of a nanostructured iron polysaccharide produced anaerobically by a
      strain of Klebsiella oxytoca.
AB  - A strain of Klebsiella oxytoca, isolated from acid pyrite-mine drainage,
      characteristically produces a ferric hydrogel, consisting of branched
      heptasaccharide repeating units exopolysaccharide (EPS), with metal content of 36
      wt%. The high content of iron in the EPS matrix cannot be explained by a simple
      ferric ion bond to the sugar skeleton. The bio-generated Fe-EPS is investigated
      by X-ray absorption spectroscopy. Fe K-edge XANES analysis shows that iron is
      mostly in trivalent form, with a non-negligible amount of Fe(2+) in the
      structure. The Fe EXAFS results indicate that iron in the sample is in a
      mineralized form, prevalently in the form of nano-sized particles of iron
      oxides/hydroxides, most probably a mixture of different nano-crystalline forms.
      TEM shows that these nanoparticles are located in the interior of the EPS matrix,
      as in ferritin. The strain produces Fe-EPS to modulate Fe-ions uptake from the
      cytoplasm to avoid iron toxicity under anaerobic conditions. This microbial
      material is potentially applicable as iron regulator.

PMID- 22585085
TI  - Unraveling the Amycolatopsis tucumanensis copper-resistome.
AB  - Heavy metal pollution is widespread causing serious ecological problems in many
      parts of the world; especially in developing countries where a budget for
      remediation technology is not affordable. Therefore, screening for microbes with
      high accumulation capacities and studying their stable resistance characteristics
      is advisable to define cost-effective any remediation strategies. Herein, the
      copper-resistome of the novel copper-resistant strain Amycolatopsis tucumanensis
      was studied using several approaches. Two dimensional gel electrophoresis
      revealed that proteins of the central metabolism, energy production,
      transcriptional regulators, two-component system, antioxidants and protective
      metabolites increased their abundance upon copper-stress conditions.
      Transcriptome analysis revealed that in presence of copper, superoxide dismutase,
      alkyl hydroperoxide reductase and mycothiol reductase genes were markedly induced
      in expression. The oxidative damage of protein and lipid from A. tucumanensis was
      negligible compared with that observed in the copper-sensitive strain
      Amycolatopsis eurytherma. Thus, we provide evidence that A. tucumamensis shows a
      high adaptation towards copper, the sum of which is proposed as the copper
      resistome. This adaptation allows the strain to accumulate copper and survive
      this stress; besides, it constitutes the first report in which the copper
      resistome of a strain of the genus Amycolatopsis with bioremediation potential
      has been evaluated.

PMID- 22585086
TI  - (1)H, (13)C and (15)N backbone and side-chain resonance assignments of reduced
      CcmG from Escherichia coli.
AB  - CcmG is a periplasmic, membrane-anchored protein widely distributed in a variety
      of species. In Escherichia coli, the CcmG protein always acts as a weak reductant
      in the electron transport chain during cytochrome c maturation (Ccm). Here we
      report (1)H, (15)N and (13)C backbone and side-chain resonance assignments of the
      reduced CcmG protein (residues 19-185, renumbered as 1-167) from E. coli. This
      work lays the essential basis for the further structural and functional analysis
      of reduced CcmG.

PMID- 22585087
TI  - 1H, 13C and 15N chemical shift assignments for an intracellular proteinase
      inhibitor of Bacillus subtilis.
AB  - Intracellular proteinases (ISPs) are the main component of the bacilli degradome
      and a distinctive class in different bacilli. An intracellular proteinase
      inhibitor of the bacteria Bacillus subtillis was shown to regulate the activity
      of ISP-1. To study the structure of this inhibitor, we report the resonance
      assignment for this protein with 119 amino acid. The data will allow us to
      perform structural study on this inhibitor to understand its mechanism for ISP-1
      inhibition. 

PMID- 22585088
TI  - 1H, 13C and 15N resonance assignments and second structure information of Gad m
      1: a beta-parvalbumin allergen from Atlantic cod (Gadus morhua).
AB  - Gad m 1 is the major allergen from Atlantic cod. It belongs to beta-parvalbumin
      protein family and is characterized by the presence of two calcium-binding sites
      so called EF-hand motifs. beta-Parvalbumins such as Gad m 1 are the most
      important fish allergens and their high cross-reactivity is the cause of the
      observed polysensitization to various fish species in allergic patients. Despite
      extensive efforts, the complete elucidation of beta-parvalbumin-IgE complexes has
      not been achieved yet. Allergen structural studies are essential for the
      development of novel immunotherapy strategies, including vaccination with
      hypoallergenic derivatives and chimeric molecules. Here, we report for the first
      time the NMR study of a beta-parvalbumin: Gad m 1. This report includes: (1)H,
      (13)C and (15)N resonance assignments of Gad m 1 as well as the second structure
      information based on the (13)C chemical shifts. 

PMID- 22585089
TI  - Metabolic and neuroendocrine responses to Roux-en-Y gastric bypass. I: energy
      balance, metabolic changes, and fat loss.
AB  - CONTEXT: Obesity is a major health problem. Effective treatment requires
      understanding the homeostatic responses to caloric restriction. OBJECTIVE: The
      aim was to study Roux-en-Y gastric bypass patients longitudinally for 6 months
      after surgery to identify major factors modulating fat loss. METHODS: We studied
      13 patients (11 females and two males) aged 41.2 +/- 2 yr. Mean body mass index
      was 44.6 +/- 1.2 kg/m(2), with 50 +/- 1% body fat (58.3 kg). Selection excluded
      patients with confounding comorbidities or treatments. RESULTS: Caloric intake
      was reduced 742 +/- 82 kcal/d by 1 month and 450 kcal/d between 2 and 4 months
      postoperatively. By 6 months, relative to baseline, body mass index decreased
      24.8 +/- 1.1%; percentage body fat, 37.3 +/- 3.2% (21.7 kg); fat free mass (FFM),
      9.7 +/- 1.2%; and resting metabolic rate (RMR), 18.1 +/- 4.3%. RMR correlated
      with FFM at all times (r = 0.71; P < 0.0001), but FFM explained no more than 50%
      of RMR variance. Exercise capacity (treadmill walking, 53 m/min with increasing
      grade) improved with time. Mean nonexercise physical activity level was low (1.2,
      or 20% of RMR), with considerable variance among individuals. Fat loss did not
      correlate with the aggregate energy deficit or its individual components. Resting
      or postexercise respiratory exchange ratio (RER) was lowest, whereas plasma beta
      OH-butyrate and glycerol were highest, between 1 and 2 months after surgery. RER
      increased linearly with mild exercise, and fat loss correlated positively with
      physical activity level and RER. CONCLUSIONS: Although the ultimate cause for
      weight loss is the energy deficit, the variance in fat loss correlated with
      glucose oxidation, suggesting that glucose partition between oxidation (muscle)
      and storage (adipose tissue) is an important factor affecting fat loss in
      individuals submitted to Roux-en-Y gastric bypass.

PMID- 22585090
TI  - Factors predicting vitamin D response variation in non-Hispanic white
      postmenopausal women.
AB  - OBJECTIVE: It is well documented that there is wide variation in the response of
      serum 25-hydroxyvitamin D [25(OH)D] to a given dose of vitamin D supplementation.
      Understanding factors affecting the response variation is important for
      identifying subjects who are susceptible to vitamin D deficiency or toxicity.
      This study aimed to evaluate potential predictors for vitamin D response
      variation. DESIGN AND PARTICIPANTS: A total of 1179 non-Hispanic white
      postmenopausal women were enrolled into a 4-yr calcium and vitamin D (1100 IU/d)
      clinical trial. Among them, serum 25(OH)D level of 1063 subjects were measured at
      both baseline and after 12 months treatment. Vitamin D response was computed for
      these 1063 subjects as the difference in levels of serum 25(OH)D concentration at
      the end of a 12-month vitamin D treatment compared with baseline. Stepwise linear
      regression was used to identify predictors of vitamin D response variation.
      RESULTS: Increase in vitamin D intake, baseline serum 25(OH)D level, baseline
      blood collection season, baseline serum calcium level, and baseline body mass
      index were predictors of vitamin D response variation. These five factors
      explained 46.8% of the vitamin D response variation in the 1063 subjects. The
      first three factors [increase in vitamin D intake, baseline serum 25(OH)D level,
      baseline blood collection season] remained as predictors in the 392 subjects with
      trial vitamin D supplementation. For the first time, our study indicated that
      season is an important prediction factor for vitamin D response variation.
      Subjects who started vitamin D treatment in a cold season (autumn and winter)
      achieved a significantly higher serum 25(OH)D increase than those started in a
      hot season (summer) (P < 0.001). CONCLUSION: Our study suggests that the increase
      in vitamin D supplementation, baseline serum 25(OH)D level, and the season when
      initiating the vitamin D supplementation can partially predict vitamin D response
      variation in non-Hispanic postmenopausal women.

PMID- 22585091
TI  - Differential gene expression by oxyphil and chief cells of human parathyroid
      glands.
AB  - CONTEXT: Parathyroid oxyphil cells, whose function is unknown, are thought to be
      derived from chief cells. Oxyphil cells increase in number in parathyroid glands
      of patients with chronic kidney disease (CKD) and are even more abundant in
      patients receiving treatment for hyperparathyroidism with calcitriol and/or the
      calcimimetic cinacalcet. OBJECTIVE: We examined oxyphil and chief cells of
      parathyroid glands of CKD patients for differential expression of genes important
      to parathyroid function. DESIGN/SETTING/PARTICIPANTS: Parathyroid tissue from CKD
      patients with refractory hyperparathyroidism was immunostained for gene
      expression studies. MAIN OUTCOME MEASURE: Immunostaining for PTH, PTHrP, calcium
      sensing receptor, glial cells missing 2, vitamin D receptor, 25-hydroxyvitamin D
      1alpha-hydroxylase, and cytochrome c was quantified and expression reported for
      oxyphil and chief cells. RESULTS: Expression of all proteins analyzed, except for
      the vitamin D receptor, was higher in oxyphil cells than in chief cells.
      CONCLUSION: Human parathyroid oxyphil cells express parathyroid-relevant genes
      found in the chief cells and have the potential to produce additional
      autocrine/paracrine factors, such as PTHrP and calcitriol. Additional studies are
      warranted to define the secretory properties of these cells and clarify their
      role in parathyroid pathophysiology.

PMID- 22585092
TI  - Gene expression profiling identifies ESRP1 as a potential regulator of epithelial
      mesenchymal transition in somatotroph adenomas from a large cohort of patients
      with acromegaly.
AB  - CONTEXT: The epithelial marker E-cadherin plays a crucial role in epithelial
      mesenchymal transition (EMT). Decreased protein content in somatotroph adenomas
      has been associated with increased tumor size, invasion, and poor response to
      somatostatin analog (SA) treatment, but the potential mechanisms of EMT
      progression in these adenomas are lacking. OBJECTIVE: We hypothesized that
      characterization of EMT-related transcripts in somatotroph adenomas could
      identify novel therapeutic targets in individuals with poor response to SA
      treatment and provide more knowledge of the mechanism of EMT progression.
      PATIENTS: Fifty-three patients with acromegaly participated in the study.
      RESEARCH DESIGN AND METHODS: We performed microarray analysis of 16 adenomas,
      eight with high expression and eight with low expression of E-cadherin, in order
      to identify EMT-related transcripts. Candidate transcripts were further explored
      in vivo in 53 adenomas and in vitro in a rat pituitary GH-producing cell (GH3)
      after exploring three models for reducing E-cadherin and inducing a mesenchymal
      phenotype. RESULTS: In vivo E-cadherin mRNA expression in tumor tissue is
      associated negatively with tumor size and invasiveness and positively with GH and
      IGF-I levels in serum and response to SA treatment. Microarray and subsequent PCR
      analysis identify several EMT-related genes associated with E-cadherin
      expression. In vitro, few of these EMT-related genes were regulated by silencing
      E-cadherin or by TGF-beta1 treatment in GH3 cells. In contrast, silencing Esrp1
      in GH3 cells regulated many of the EMT-related transcripts. CONCLUSION: These
      results indicate that ESRP1 could be a master regulator of the EMT process in
      pituitary adenomas causing acromegaly.

PMID- 22585093
TI  - Proline protects liver from D-galactosamine hepatitis by activating the IL
      6/STAT3 survival signaling pathway.
AB  - The oral administration of proline, one of the non-essential amino acids, has
      been shown to effectively protect the liver from D-galactosamine (GalN)-induced
      liver injury and to improve the survival rate. The aim of this study was to
      investigate the mechanism of this protective action of proline. We paid
      particular attention to the effect of proline on inflammatory activation,
      regenerative response, and the associated signal transduction in the liver. Male
      Fischer rats received intraperitoneal injections of GalN (1.4 g/kg) with or
      without the oral administration of proline (2 g/kg) 1 h before GalN treatment.
      Liver pathology, plasma indices of inflammation, and the level of proliferative
      marker in the liver were monitored. The hepatic activation of interleukin-6 (IL
      6)/signal transducer and activator of transcription (STAT)-3 pathway, which is
      downstream of tumor necrosis factor (TNF)-alpha/nuclear factor-kappaB, was also
      studied. GalN induced massive inflammatory expansion in the liver, leading to a
      high death rate (60 %) more than 72 h after the treatment. Proline administration
      significantly suppressed inflammatory infiltration in the live after 48 h, which
      was accompanied by depletion of plasma TNF-alpha, glutamic oxaloacetic
      transaminase, and glutamic pyruvic transaminase. The mRNA expression of histone
      H3, a marker of proliferation, was significantly upregulated in the liver of
      proline-treated animals. Furthermore, IL-6/STAT-3 pathway, an anti-inflammatory
      and regenerative signaling pathway, was strongly activated prior to these
      observations, with the upregulated expression of downstream genes. These results
      suggest that the tissue-protective mechanism of proline involves the early
      activation of IL-6/STAT-3 pathway in the liver, with subsequent activation of the
      regenerative response and suppression of massive inflammatory activation.

PMID- 22585096
TI  - Design and estimation of coded exposure point spread functions.
AB  - We address the problem of motion deblurring using coded exposure. This approach
      allows for accurate estimation of a sharp latent image via well-posed
      deconvolution and avoids lost image content that cannot be recovered from images
      acquired with a traditional shutter. Previous work in this area has used either
      manual user input or alpha matting approaches to estimate the coded exposure
      Point Spread Function (PSF) from the captured image. In order to automate
      deblurring and to avoid the limitations of matting approaches, we propose a
      Fourier-domain statistical approach to coded exposure PSF estimation that allows
      us to estimate the latent image in cases of constant velocity, constant
      acceleration, and harmonic motion. We further demonstrate that previously used
      criteria to choose a coded exposure PSF do not produce one with optimal
      reconstruction error, and that an additional 30 percent reduction in Root Mean
      Squared Error (RMSE) of the latent image estimate can be achieved by
      incorporating natural image statistics.

PMID- 22585094
TI  - Stabilizing group treatment for complex posttraumatic stress disorder related to
      child abuse based on psychoeducation and cognitive behavioural therapy: a
      multisite randomized controlled trial.
AB  - BACKGROUND: Evidence-based treatments for complex posttraumatic stress disorder
      (PTSD) related to childhood abuse are scarce. This is the first randomized
      controlled trial to test the efficacy of psycho-educational and cognitive
      behavioural stabilizing group treatment in terms of both PTSD and complex PTSD
      symptom severity. METHODS: Seventy-one patients with complex PTSD and severe
      comorbidity (e.g., 74% axis II comorbidity) were randomly assigned to either a 20
      week group treatment in addition to treatment as usual or to treatment as usual
      only. Primary outcome measures were the Davidson trauma scale (DTS) for PTSD and
      the structured interview for disorders of extreme stress (SIDES) for complex PTSD
      symptoms. Statistical analysis was conducted in the intention-to-treat (ITT) and
      in the completer sample. Subjects were considered responders when scoring at 20
      weeks at least 1 standard deviation below pretest findings. RESULTS: The 16%
      attrition was relatively low. After 20 weeks, the experimental condition (large
      effect sizes) and control condition (medium effect sizes) both showed significant
      decreases on the DTS and SIDES, but differences between the conditions were not
      significant. The secondary responder analysis (ITT) revealed significantly more
      responders on the DTS (45 vs. 21%), but not on the SIDES (61 vs. 42%).
      CONCLUSIONS: Adding psycho-educational and cognitive behavioural stabilizing
      group treatment for complex PTSD related to child abuse to treatment as usual
      showed an equivocal outcome. Patients in both conditions improved substantially
      during stabilizing treatment, and while significant superiority on change scores
      was absent, responder analysis suggested clinical meaningfulness of adding group
      treatment.

PMID- 22585095
TI  - Microbes as targets and mediators of allelopathy in plants.
AB  - Studies of allelopathy in terrestrial systems have experienced tremendous growth
      as interest has risen in describing biochemical mechanisms responsible for
      structuring plant communities, determining agricultural and forest productivity,
      and explaining invasive behaviors in introduced organisms. While early criticisms
      of allelopathy involved issues with allelochemical production, stability, and
      degradation in soils, an understanding of the chemical ecology of soils and its
      microbial inhabitants has been increasingly incorporated in studies of
      allelopathy, and recognized as an essential predictor of the outcome of
      allelopathic interactions between plants. Microbes can mediate interactions in a
      number of ways with both positive and negative outcomes for surrounding plants
      and plant communities. In this review, we examine cases where soil microbes are
      the target of allelopathic plants leading to indirect effects on competing
      plants, provide examples where microbes play either a protective effect on plants
      against allelopathic competitors or enhance allelopathic effects, and we provide
      examples where soil microbial communities have changed through time in response
      to allelopathic plants with known or potential effects on plant communities. We
      focus primarily on interactions involving wild plants in natural systems, using
      case studies of some of the world's most notorious invasive plants, but we also
      provide selected examples from agriculturally managed systems. Allelopathic
      interactions between plants cannot be fully understood without considering
      microbial participants, and we conclude with suggestions for future research.

PMID- 22585097
TI  - Iterative closest normal point for 3D face recognition.
AB  - The common approach for 3D face recognition is to register a probe face to each
      of the gallery faces and then calculate the sum of the distances between their
      points. This approach is computationally expensive and sensitive to facial
      expression variation. In this paper, we introduce the iterative closest normal
      point method for finding the corresponding points between a generic reference
      face and every input face. The proposed correspondence finding method samples a
      set of points for each face, denoted as the closest normal points. These points
      are effectively aligned across all faces, enabling effective application of
      discriminant analysis methods for 3D face recognition. As a result, the
      expression variation problem is addressed by minimizing the within-class
      variability of the face samples while maximizing the between-class variability.
      As an important conclusion, we show that the surface normal vectors of the face
      at the sampled points contain more discriminatory information than the
      coordinates of the points. We have performed comprehensive experiments on the
      Face Recognition Grand Challenge database, which is presently the largest
      available 3D face database. We have achieved verification rates of 99.6 and 99.2
      percent at a false acceptance rate of 0.1 percent for the all versus all and ROC
      III experiments, respectively, which, to the best of our knowledge, have seven
      and four times less error rates, respectively, compared to the best existing
      methods on this database.

PMID- 22585098
TI  - A framework for mining signatures from event sequences and its applications in
      healthcare data.
AB  - This paper proposes a novel temporal knowledge representation and learning
      framework to perform large-scale temporal signature mining of longitudinal
      heterogeneous event data. The framework enables the representation, extraction,
      and mining of high-order latent event structure and relationships within single
      and multiple event sequences. The proposed knowledge representation maps the
      heterogeneous event sequences to a geometric image by encoding events as a
      structured spatial-temporal shape process. We present a doubly constrained
      convolutional sparse coding framework that learns interpretable and shift
      invariant latent temporal event signatures. We show how to cope with the sparsity
      in the data as well as in the latent factor model by inducing a double sparsity
      constraint on the beta-divergence to learn an overcomplete sparse latent factor
      model. A novel stochastic optimization scheme performs large-scale incremental
      learning of group-specific temporal event signatures. We validate the framework
      on synthetic data and on an electronic health record dataset.

PMID- 22585099
TI  - A fast algorithm for multidimensional ellipsoid-specific fitting by minimizing a
      new defined vector norm of residuals using semidefinite programming.
AB  - A quadratic surface in n-dimensional space is defined as the locus of zeros of a
      quadratic polynomial. The quadratic polynomial may be compactly written in
      notation by an (n+1)-vector and a real symmetric matrix of order n+1, where the
      vector represents homogenous coordinates of an n-D point, and the symmetric
      matrix is constructed from the quadratic coefficients. If an n-D quadratic
      surface is an n-D ellipsoid, the leading n * n principal submatrix of the
      symmetric matrix would be positive or opposite definite. As we know, to impose a
      matrix being positive or opposite definite, perhaps the best choice may be to
      employ semidefinite programming (SDP). From such straightforward and intuitive
      knowledge, in the literature until 2002, Calafiore first proposed a feasible
      method for multidimensional ellipsoid-specific fitting using SDP, which minimizes
      the 2--norm of the algebraic residual vector. However, the runtime of the method
      is significantly long and memory is often out when the number of fitted points is
      greater than several thousand. In this paper, we propose a fast and easily
      implemented algorithm for multidimensional ellipsoid-specific fitting by
      minimizing a new defined vector norm of the algebraic residual vector using SDP,
      which drastically decreases the size of the SDP problem while preserving
      accuracy. The proposed fast method can handle several million fitted points
      without any difficulty.

PMID- 22585100
TI  - Trainable COSFIRE filters for keypoint detection and pattern recognition.
AB  - BACKGROUND: Keypoint detection is important for many computer vision
      applications. Existing methods suffer from insufficient selectivity regarding the
      shape properties of features and are vulnerable to contrast variations and to the
      presence of noise or texture. METHODS: We propose a trainable filter which we
      call Combination Of Shifted FIlter REsponses (COSFIRE) and use for keypoint
      detection and pattern recognition. It is automatically configured to be selective
      for a local contour pattern specified by an example. The configuration comprises
      selecting given channels of a bank of Gabor filters and determining certain blur
      and shift parameters. A COSFIRE filter response is computed as the weighted
      geometric mean of the blurred and shifted responses of the selected Gabor
      filters. It shares similar properties with some shape-selective neurons in visual
      cortex, which provided inspiration for this work. RESULTS: We demonstrate the
      effectiveness of the proposed filters in three applications: the detection of
      retinal vascular bifurcations (DRIVE dataset: 98.50 percent recall, 96.09 percent
      precision), the recognition of handwritten digits (MNIST dataset: 99.48 percent
      correct classification), and the detection and recognition of traffic signs in
      complex scenes (100 percent recall and precision). CONCLUSIONS: The proposed
      COSFIRE filters are conceptually simple and easy to implement. They are versatile
      keypoint detectors and are highly effective in practical computer vision
      applications.

PMID- 22585101
TI  - Simultaneous cast shadows, illumination and geometry inference using hypergraphs.
AB  - The cast shadows in an image provide important information about illumination and
      geometry. In this paper, we utilize this information in a novel framework in
      order to jointly recover the illumination environment, a set of geometry
      parameters, and an estimate of the cast shadows in the scene given a single image
      and coarse initial 3D geometry. We model the interaction of illumination and
      geometry in the scene and associate it with image evidence for cast shadows using
      a higher order Markov Random Field (MRF) illumination model, while we also
      introduce a method to obtain approximate image evidence for cast shadows.
      Capturing the interaction between light sources and geometry in the proposed
      graphical model necessitates higher order cliques and continuous-valued
      variables, which make inference challenging. Taking advantage of domain
      knowledge, we provide a two-stage minimization technique for the MRF energy of
      our model. We evaluate our method in different datasets, both synthetic and real.
      Our model is robust to rough knowledge of geometry and inaccurate initial shadow
      estimates, allowing a generic coarse 3D model to represent a whole class of
      objects for the task of illumination estimation, or the estimation of geometry
      parameters to refine our initial knowledge of scene geometry, simultaneously with
      illumination estimation.

PMID- 22585102
TI  - My back has shrunk: the influence of traditional cupping on body image in
      patients with chronic non-specific neck pain.
AB  - BACKGROUND: In conditions such as phantom limb pain and low back pain body image
      is distorted. This qualitative study investigates body image in patients with
      chronic non-specific neck pain (CNP), its influence on their everyday life and
      any changes linked to traditional cupping therapy. METHODS: The study was
      conducted with a convenience sample of 6 patients with CNP from a larger
      randomised controlled trial (RCT) on cupping. The data came from body image
      drawings and semi-structured interviews. The latter were analysed using Mayring's
      content analysis techniques. RESULTS: The patients' drawings showed apparent body
      image distortions with elements that were missing or deformed. The interviews
      showed that pain was the predominant perception, influencing patients' body
      perception. Patients saw their pain as beyond their control, using mostly passive
      strategies to cope. After cupping, patients reported less pain and improved pain
      perception. These changes were reflected in their drawings. CONCLUSION: Patients
      with CNP experienced apparent body image distortions, which traditional cupping
      therapy appeared to improve. Additional research is needed to further explore
      this link.

PMID- 22585103
TI  - Clay jojoba oil facial mask for lesioned skin and mild acne--results of a
      prospective, observational pilot study.
AB  - BACKGROUND: External application of clay facial masks is a cosmetic procedure
      generally used to reduce skin lesions and to improve overall skin condition.
      OBJECTIVE: Collecting pilot data about self-treatment with clay jojoba oil masks
      on participants with acne-prone, lesioned skin and acne. METHODS: Open,
      prospective, observational pilot study: Participants received written
      information, instructions, and questionnaires without direct contact with the
      study physician. For 6 weeks, they applied the masks 2-3 times per week. The
      primary outcome is the difference of skin lesions: baseline vs. after 6 weeks.
      RESULTS: 194 participants (192 female, 2 male, mean age (+/- SE) (32.3 +/- 0.7
      years) returned questionnaires and diaries. 133 of these participants returned
      complete and precise lesion counts (per-protocol (PP) collective). A 54% mean
      reduction in total lesion count was observed after 6 weeks of treatment with clay
      facial mask. Both inflammatory and non-inflammatory skin lesions were reduced
      significantly after treatment compared to baseline: Median counts (MC) of
      pustules per affected participant were reduced from 7.0 +/- 0.9 to 3.0 +/- 0.5
      (mean individual reduction (MIR) = 49.4%), the MC of the papules from 3.5 +/- 2.2
      to 1.0 +/- 0.4 (MIR = 57.3%), the MC of cysts from 2.0 +/- 0.8 to 0.5 +/- 0.4
      (MIR = 68.6%) and the MC of comedones from 26.5 +/- 6.3 to 16.0 +/- 4.0 (MIR =
      39.1%). DLQI-average score decreased from 5.0 +/- 4.5 (mean +/- SE) before to 2.1
      +/- 2.8 after treatment. CONCLUSIONS: The present study gives preliminary
      evidence that healing clay jojoba oil facial masks can be effective treatment for
      lesioned skin and mild acne vulgaris.

PMID- 22585104
TI  - Temporal changes in tongue color as criterion for tongue diagnosis in Kampo
      medicine.
AB  - BACKGROUND: In Kampo medicine (Japanese traditional herbal medicine), the
      appearance of the tongue contains a lot of useful information for diagnosis.
      However, an inspection of the tongue is not considered to be important in modern
      medical diagnosis, since the skills applied in the examination are difficult to
      understand. Thus, we developed an imaging system and algorithm for quantitative
      analysis of the tongue to provide the traditional techniques of Kampo with
      greater objectivity. MATERIALS AND METHODS: Tongue images were taken from 9
      healthy subjects for 3 consecutive weeks (5 days/week), 12 times a day, with 300
      images taken successively within 30 s each time. Then, the temporal color changes
      in 30 s, 1 day, and 3 weeks were measured in the device-independent International
      Commission on Illumination (CIE) 1976 L*a*b* color space. RESULTS: The tongue
      color change in 30 s varied between individuals, and it was mainly classified
      into 3 patterns. This image acquisition system and valid color management should
      help all tongue-related research, and the 30-s temporal color change might be an
      important target for further tongue analysis. CONCLUSIONS: We were able to
      acquire tongue images without specular reflection and with valid color
      reproduction, and the color change in 30 s was found to vary. Tongue color
      changes have not been mentioned in the classics of Kampo medicine, since they
      were certainly impossible to discriminate by the naked eye. The change during 30
      s is a new finding based on the electronic devices, and together they are
      expected to become a new criterion for tongue analysis.

PMID- 22585105
TI  - [On the relationship of psychosomatic and mind-body medicine: integrative,
      complementary or alternative disciplines within an evolutionary approach?].
AB  - The text outlines the relation between psychosomatic medicine as an established
      medical discipline and the emerging concept of mind-body medicine from a
      historical, clinical and epistemological perspective. Limitations and
      contributions of both disciplines are discussed and the opportunities within the
      concept of Integrative Medicine are outlined. Whereas psychosomatic medicine is
      perceived as a form of transformation through a primarily verbal discoursive
      relationship, mind-body medicine claims healing through increased traditional
      techniques of the relaxation response, increased awareness, mindfulness,
      increasing des-identification and health-promoting lifestyle modification. It
      becomes clear that mind-body medicine seems to be epistemologically the broader
      theoretical framework, whereas in a clinical context the combination of both
      disciplines appears to be complementary and synergistic. The connection between
      psychosomatic medicine and mind-body medicine can make an important and exemplary
      contribution to the concept of Integrative Medicine.

PMID- 22585106
TI  - [Traditional use: phytopharmaceuticals seen from a historical perspective].
AB  - In phytopharmacy, the term 'traditional use' is widely found in colloquial
      language but has also great significance for registration procedures of medicinal
      products. It is therefore justified to explore its actual meaning from the
      perspective of social and pharmaceutical history. It is shown that a tradition is
      founded by transmission of knowledge and techniques over at least three
      generations, while the life span of a generation may vary widely. Changes and
      adaptations to technical advancements do not at all avoid but even constitute the
      development of traditions. Historical research provides valuable knowledge about
      effectiveness and risk of phytopharmaceuticals. Criteria of traditional use may
      complement but not substitute modern evidence based methods; however they always
      need to be applied historically sound.

PMID- 22585109
TI  - The relationship between forgiveness, spirituality, traumatic guilt and
      posttraumatic stress disorder (PTSD) among people with addiction.
AB  - Spirituality and forgiveness have been shown to be associated with psychological
      well-being, while guilt has been associated with poor health. Little is known,
      however, about the relationship between forgiveness, spirituality, guilt,
      posttraumatic stress (PTSD) and psychological co-morbidity among people in
      recovery from addiction. Eighty-one people (F = 36, M = 45) in recovery from drug
      and alcohol addiction were recruited from two residential units and two drop-in
      centres in a city in the United Kingdom. They completed the Posttraumatic Stress
      Diagnostic Scale (PDS), the General Health Questionnaire-28 (GHQ-28), the
      Spiritual Involvement and Beliefs Scale (SIBS), the Heartland Forgiveness Scale
      (HFS), the Traumatic Guilt Inventory (TGI), the Michigan Alcoholism Screening
      Test (MAST-22) and the Drug Abuse Screening Test (DAST-20). The control group
      comprised of 83 (F = 34, M = 49) individuals who confirmed that they did not have
      addiction and completed the PDS & GHQ-28. 54 % of the addiction group met the
      criteria for full PTSD and reported anxiety, somatic problems and depression.
      They described themselves as spiritual, had strong feelings of guilt associated
      with their addiction, and had difficulty in forgiving themselves. Controlling for
      demographics, number of events and medication management, regression analyses
      showed that spirituality predicted psychological co-morbidity, whilst feelings of
      guilt predicted PTSD symptoms and psychological co-morbidity. Unexpectedly,
      forgiveness did not predict outcomes. This study supports existing literature,
      which shows that people with drug and alcohol addiction tend to have experienced
      significant past trauma and PTSD symptoms. Their posttraumatic stress reactions
      and associated psychological difficulties can be better understood in the light
      of guilt and spirituality. Meanwhile, their ability to forgive themselves or
      others did not seem to influence health outcomes.

PMID- 22585111
TI  - [Not Available].

PMID- 22585108
TI  - Guiding plant virus particles to integrin-displaying cells.
AB  - Viral nanoparticles (VNPs) are structurally regular, highly stable, tunable
      nanomaterials that can be conveniently produced in high yields. Unmodified VNPs
      from plants and bacteria generally do not show tissue specificity or high
      selectivity in binding to or entry into mammalian cells. They are, however,
      malleable by both genetic and chemical means, making them useful scaffolds for
      the display of large numbers of cell- and tissue-targeting ligands, imaging
      moieties, and/or therapeutic agents in a well-defined manner. Capitalizing on
      this attribute, we modified the genetic sequence of the Cowpea mosaic virus
      (CPMV) coat protein to display an RGD oligopeptide sequence derived from human
      adenovirus type 2 (HAdV-2). Concurrently, wild-type CPMV was modified via NHS
      acylation and Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) chemistry to
      attach an integrin-binding cyclic RGD peptide. Both types of particles showed
      strong and selective affinity for several different cancer cell lines that
      express RGD-binding integrin receptors.

PMID- 22585110
TI  - Impact of psychiatrists' qualifications on the rate of compulsory admissions.
AB  - Despite efforts to reduce coercion in psychiatry, involuntary hospitalizations
      remain frequent, representing more than half of all admissions in some European
      regions. Since October 2006, only certified psychiatrists are authorized to
      require a compulsory admission to our facility, while before all physicians were,
      including residents. The aim of the present study is to assess the impact of this
      change of procedure on the proportion compulsory admissions. All medical records
      of patients admitted respectively 4 months before and 4 month after the
      implementation of the procedure were retrospectively analyzed. This search
      retrieved a total of 2,227 hospitalizations for 1,584 patients. The overall
      proportions of compulsory and voluntary admissions were 63.9 % and 36.1 %
      respectively. The average length of stay was 32 days (SD +/- 64.4). During the
      study period, 25 % of patients experienced two hospitalizations or more. The most
      frequent patients' diagnoses were affective disorders (30 %), psychotic disorders
      (18.4 %) and substance abuse disorders (15.7 %). Compared with the period before
      October 2006, patients hospitalized from October 2006 up were less likely to be
      hospitalized on a compulsory basis (OR = 0.745, 95 % CI: 0.596-0.930). Factors
      associated with involuntary admission were young age (20 years or less), female
      gender, a diagnosis of psychotic disorder and being hospitalized for the first
      time. Our results strongly suggest that limiting the right to require compulsory
      admissions to fully certified psychiatrists can reduce the rate of compulsory
      versus voluntary admissions.

PMID- 22585112
TI  - Unsafe in the camouflage tower: sexual victimization and perceptions of military
      academy leadership.
AB  - Few studies have examined sexual victimization among cadets and midshipmen at the
      three U.S. Military Academies. Self-report data from the 2005 Service Academy
      Sexual Assault Survey of Cadets and Midshipmen (n = 5,220) were used to examine
      the extent of unwanted sexual attention, sexual harassment, unwanted sexual
      contact, sexual coercion, and rape within the last academic year and their
      effects on cadets' and midshipmen's perceptions of their leadership's morality
      and intolerance for sexual victimization. About 60% of cadets and midshipmen
      experienced at least one type of sexual victimization and 25% reported that they
      had experienced polyvictimization (e.g., two or more types). Eighty-six percent
      of female and 42% of male cadets and midshipmen were sexually victimized. Those
      who were sexually victimized had significantly more negative views of their
      leadership's morality and intolerance for sexual victimization than nonvictims.
      Cadets and midshipmen who reported experiencing polyvictimization were more
      likely to perceive leadership as less moral and more tolerant of sexual
      victimization than those experiencing a single type. This pattern also was
      observed for gender-specific models; both male and female victims reported more
      negative perceptions of leadership. Implications concerning the effects of sexual
      victimization on military leadership are discussed.

PMID- 22585113
TI  - Peer physical aggression and its association with aggressive beliefs, empathy,
      self-control, and cooperation skills among students in a rural town of China.
AB  - This study explored the prevalence of peer physical aggression (PPA) and its
      association with aggressive beliefs, empathy, self-control, and cooperation
      skills among 1,719 7th-to-9th-grade students in a rural town in the central China
      province of Henan. The data were collected by the self-administered questionnaire
      anonymously. Results showed that 17.9% of the students reported that they had one
      or more times of physical aggressive behaviors toward their peers in the past 12
      months. The reported rate of PPA was significantly higher in boys (24.7%) than in
      girls (10.7%). After adjusting the factors of gender and grade, result of
      logistic regression analysis showed that having a higher level of aggressive
      beliefs was PPA risk factor; a higher level of self-control was protective
      factor, but there were no significant association between PPA and the factors of
      empathy and cooperation skills. These results indicated that helping students to
      decrease their aggressive beliefs and to improve their self-control skill would
      aid in the prevention of youth violence.

PMID- 22585114
TI  - Patterns of injuries in domestic violence in a Romanian population.
AB  - In Romania, the quantification of traumatic injuries is achieved in medical-
      legal services; therefore, each domestic violence (DV) victim needs a medical
      legal certificate to prove in a court of law the presence of traumatic injuries.
      In this study, we aimed to determine the pattern of traumatic injuries in DV. A
      total of 219 consecutive DV cases were included. For each victim, a detailed
      medical-legal examination was performed, including specialized consults, if
      needed. Results were analyzed statistically using the SPSS software. Traumatic
      injuries in DV cases were usually located in the head, face, and neck areas and
      had a low severity index. Severe lesions were found in less than 10% and no
      sexual aggression was found. The severity increases with age and is higher for
      males than females. The pattern of DV-associated injuries we have encountered is
      similar to the one found in other similar studies. Knowing this pattern may be
      useful in clinical practice to detect cases of DV.

PMID- 22585115
TI  - Voices of strength and struggle: women's coping strategies against spousal
      violence in Pakistan.
AB  - This article documents the coping strategies adopted by women victims of spousal
      violence in Pakistan. By drawing on 21 in-depth interviews conducted in Lahore
      and Sialkot (Pakistan), we found that the women tried to cope with violence by
      using various strategies, both emotion focused (e.g., use of religion, placating
      the husband, etc.) and problem focused (e.g., seeking support from formal
      institutions, etc.). The data showed that a majority of the women used emotion
      focused strategies, especially spiritual therapies, which somehow reduced the
      violence and provided them with psychosocial solace. Nonetheless, these
      strategies incurred some costs, such as the consumption of scarce resources,
      time, and emotional energy. Our data also showed that few women opted for problem
      focused strategies, such as seeking help from formal institutions, as these
      strategies could lead to overt confrontation with their husbands and may result
      in divorce, the outcome least desired by most of the Pakistani women. We noted
      that the coping behavior of Pakistani women was complex, subjective, and
      nonlinear and that the boundaries between emotion-focused and problem-focused
      strategies were diffuse and blurred. Although the women never surrendered to
      violence, they were fully aware of their structural limitations and
      vulnerabilities. Being mindful of the consequences of their actions, women
      carefully tailored a combination of strategies which could be helpful in
      resisting or reducing violence but, at the same time, should not be
      counterproductive. This article argues that Pakistani women alone cannot
      effectively resist violence while living under a harshly patriarchal regime,
      where violence against women is embedded in the social, political, and legal
      structures of society. There are no quick fixes to change the status quo. The
      Pakistani government, civil society, and formal institutions must proactively
      support women in reducing their vulnerabilities and facilitate them in expanding
      their capabilities to address the real causes of violence against them.

PMID- 22585116
TI  - Extending research on the victim-offender overlap: evidence from a genetically
      informative analysis.
AB  - Criminologists have long noted that offenders are more likely to be the victims
      of crime as compared to nonoffenders. What has not been established, however, is
      why there is a significant degree of victim-offender overlap. While numerous
      explanations have been advanced and a significant number of studies have been
      conducted, there remains much to be learned about the etiology of the victim
      offender overlap. The current study pushes this line of research forward by
      offering and testing a unique hypothesis: that victimization and offending share
      a genetic etiology that leads to victim-offender overlap. Findings culled from a
      sample of sibling pairs drawn from the National Longitudinal Study of Adolescent
      Health indicated that genetic factors explained between 51% and 98% of the
      covariance between victims and offenders. Nonshared environmental factors
      explained the remaining covariance, while shared environmental factors explained
      none of the covariance. Implications and interpretations of these findings are
      considered.

PMID- 22585117
TI  - Patterns of injury and reported violence depending on relationship to assailant
      in female Swedish sexual assault victims.
AB  - Earlier studies have explored the differences between known-assailant sexual
      assaults and stranger assaults and reported the stranger assaults as being more
      violent. Only a few studies have discriminated between sexual assaults by
      intimate partners from assaults by other known assailants when comparing with
      assaults by strangers. In this study, we explored differences in the extent of
      violence and physical injury in sexual assaults committed by intimate partners
      compared with assaults by strangers and acquaintances. Medical and forensic
      records of 690 consecutive women attending a sexual assault center in Stockholm,
      Sweden were reviewed. The final sample included in the analysis consisted of 503
      patients. Our results showed that women sexually assaulted by their intimate
      partners more frequently reported physical violence (OR = 4.1) than women
      assaulted by strangers (OR = 2.0) and acquaintances (OR = 1.0). Genital injuries
      were not found to be related to the victim-assailant relationship in this study.
      Extragenital injuries showed a tendency toward being more frequently found after
      intimate partner assaults compared with stranger and acquaintance assaults;
      however, this was not found to be significant in adjusted analyses. Previous
      history of sexual assault was more common, and seeking medical care within 72 hr
      as well as being under the influence of alcohol during the assault was less
      frequent among intimate partner victims. These results support the conclusion
      that sexual assaults committed by intimate partners, contradictory to earlier
      studies, are likely to involve more physical violence and result in injuries just
      as often as assaults committed by strangers.

PMID- 22585118
TI  - Erythema nodosum.

PMID- 22585119
TI  - Blood cultures.

PMID- 22585120
TI  - Commissioning: past, present and future.

PMID- 22585121
TI  - Dengue fever: a practical guide.

PMID- 22585122
TI  - In vivo experimental stroke and in vitro organ culture induce similar changes in
      vasoconstrictor receptors and intracellular calcium handling in rat cerebral
      arteries.
AB  - Cerebral arteries subjected to different types of experimental stroke upregulate
      their expression of certain G-protein-coupled vasoconstrictor receptors, a
      phenomenon that worsens the ischemic brain damage. Upregulation of contractile
      endothelin B (ET(B)) and 5-hydroxytryptamine 1B (5-HT(1B)) receptors has been
      demonstrated after subarachnoid hemorrhage and global ischemic stroke, but the
      situation is less clear after focal ischemic stroke. Changes in smooth muscle
      calcium handling have been implicated in different vascular diseases but have not
      hitherto been investigated in cerebral arteries after stroke. Here, we evaluate
      changes of ET(B) and 5-HT(1B) receptors, intracellular calcium levels, and
      calcium channel expression in rat middle cerebral artery (MCA) after focal
      cerebral ischemia and in vitro organ culture, a proposed model of vasoconstrictor
      receptor changes after stroke. Rats were subjected to 2 h MCA occlusion followed
      by reperfusion for 1 or 24 h. Alternatively, MCAs from naive rats were cultured
      for 1 or 24 h. ET(B) and 5-HT(1B) receptor-mediated contractions were evaluated
      by wire myography. Receptor and channel expressions were measured by real-time
      PCR and immunohistochemistry. Intracellular calcium was measured by FURA-2.
      Expression and contractile functions of ET(B) and 5-HT(1B) receptors were
      strongly upregulated and slightly downregulated, respectively, 24 h after
      experimental stroke or organ culture. ET(B) receptor-mediated contraction was
      mediated by calcium from intracellular and extracellular sources, whereas 5
      HT(1B) receptor-mediated contraction was solely dependent on extracellular
      calcium. Organ culture and stroke increased basal intracellular calcium levels in
      MCA smooth muscle cells and decreased the expression of inositol triphosphate
      receptor and transient receptor potential canonical calcium channels, but not
      voltage-operated calcium channels.

PMID- 22585123
TI  - Gait adaptability training is affected by visual dependency.
AB  - As part of a larger gait adaptability training study, we designed a program that
      presented combinations of visual flow and support-surface manipulations to
      investigate the response of healthy adults to walking on a treadmill in novel
      discordant sensorimotor conditions. A visual dependence score was determined for
      each subject, and this score was used to explore how visual dependency was linked
      to locomotor performance (1) during three training sessions and (2) in a new
      discordant environment presented at the conclusion of training. Performance
      measures included reaction time (RT), stride frequency (SF), and heart rate (HR),
      which respectively served as indicators of cognitive load, postural stability,
      and anxiety. We hypothesized that training would affect performance measures
      differently for highly visually dependent individuals than for their less
      visually dependent counterparts. A seemingly unrelated estimation analysis of RT,
      SF, and HR revealed a significant omnibus interaction of visual dependency by
      session (p < 0.001), suggesting that the magnitude of differences in these
      measures across training day 1 (TD1), training day 3 (TD3), and exposure to a
      novel test is dependent on subjects' levels of visual dependency. The RT result,
      in particular, suggested that highly visually dependent subjects successfully
      trained to one set of sensory discordant conditions but were unable to apply
      their adapted skills when introduced to a new sensory discordant environment.
      This finding augments rationale for developing customized gait training programs
      that are tailored to an individual. It highlights one factor--personal level of
      visual dependency--to consider when designing training conditions for a subject
      or patient. Finally, the link between visual dependency and locomotor performance
      may offer predictive insight regarding which subjects in a normal population will
      require more training when preparing for specific novel locomotor conditions.

PMID- 22585132
TI  - Pancreatic cancer: USP9X can be used to predict pancreatic cancer outcomes.

PMID- 22585133
TI  - Colonoscopy: Reducing faecal incontinence following colonoscopy.

PMID- 22585134
TI  - Coeliac disease: Lack of consensus regarding definitions of coeliac disease.

PMID- 22585135
TI  - IBD: Optimizing vaccination strategies against HBV in patients with IBD.

PMID- 22585131
TI  - Contributions of the microbial hydrogen economy to colonic homeostasis.
AB  - Colonic gases are among the most tangible features of digestion, yet physicians
      are typically unable to offer long-term relief from clinical complaints of
      excessive gas. Studies characterizing colonic gases have linked changes in volume
      or composition with bowel disorders and shown hydrogen gas (H(2)), methane,
      hydrogen sulphide, and carbon dioxide to be by-products of the interplay between
      H(2)-producing fermentative bacteria and H(2) consumers (reductive acetogens,
      methanogenic archaea and sulphate-reducing bacteria [SRB]). Clinically, H(2) and
      methane measured in breath can indicate lactose and glucose intolerance, small
      intestinal bacterial overgrowth and IBS. Methane levels are increased in patients
      with constipation or IBS. Hydrogen sulphide is a by-product of H(2) metabolism by
      SRB, which are ubiquitous in the colonic mucosa. Although higher hydrogen
      sulphide and SRB levels have been detected in patients with IBD, and to a lesser
      extent in colorectal cancer, this colonic gas might have beneficial effects.
      Moreover, H(2) has been shown to have antioxidant properties and, in the healthy
      colon, physiological H(2) concentrations might protect the mucosa from oxidative
      insults, whereas an impaired H(2) economy might facilitate inflammation or
      carcinogenesis. Therefore, standardized breath gas measurements combined with
      ever-improving molecular methodologies could provide novel strategies to prevent,
      diagnose or manage numerous colonic disorders.

PMID- 22585136
TI  - A perfusable microfluidic device with on-chip total internal reflection
      fluorescence microscopy (TIRFM) for in situ and real-time monitoring of live
      cells.
AB  - A microfluidic device integrated with a Total Internal Reflection (TIR)-based
      chip for cell observation and analysis was developed. This integrated device
      enables in situ Total Internal Reflection Fluorescence Microscopy (TIRFM) on
      adherent cells cultured under continuous medium perfusion. This TIR-based chip,
      allows TIRFM to be easily performed on cells without the assembly of complicated
      optical components and cell culture chambers. The integrated device was evaluated
      by tracking the movement of fluorescent beads and monitoring the location of
      insulin granules in mouse pancreatic beta-cells. This system offers higher signal
      to-noise (S/N) ratio than epi-fluorescence microscopy (EPIFM), and comparable
      image quality to commercial TIRFM systems when imaging insulin granules. We also
      detected repetitive changes in intracellular Ca(2+) concentration in MIN6-m9
      cells stimulated with KCl, which demonstrates quick perfusion for cell analysis
      while maintaining high S/N ratio.

PMID- 22585138
TI  - Catalytic metal-free intramolecular hydroaminations of non-activated
      aminoalkenes: a computational exploration.
AB  - Frustrated Lewis pairs (FLPs) has been applied to catalytic metal-free
      hydrogenation. Can the FLP reactivity be used for catalytic hydroamination? Using
      density functional theory (DFT) calculations, we have explored whether the
      molecules cat1-cat3, which were previously designed by integrating the
      dearomatization-aromatization effect and the FLP reactivity, can catalyze the
      intramolecular hydroaminations of non-activated aminoalkenes to afford nitrogen
      heterocycles. The study shows that the gamma-aminoalkene (am1) hydroamination
      catalyzed by cat1 proceeds via two steps (aminoalkene N-H bond activation and C-N
      bond formation) with experimentally accessible energetics, giving the five
      membered nitrogen heterocycle product 1,1-dimethylpyrrolidine. The N-H bond
      activation is reversible. The C-N bond formation step undergoes a concerted
      mechanism and complies with the Markovnikov addition rule. Possible side
      reactions which may cause catalyst deactivation were confirmed to be
      energetically unfavorable. The molecules cat2 and cat3 are less effective than
      cat1 in catalyzing the am1 hydroamination, but the barriers are not too high. By
      following the most favorable pathway of the cat1-mediated am1 hydroamination, we
      further extended the substrate (am1) to other aminoalkenes, including the methyl
      and phenyl beta-substituted am1 (i.e. am2 and am3, respectively), the benzyl
      protected primary aminoalkene (am4), and the delta-aminoalkene (am5). The
      hydroaminations of am2 and am3 have energetics comparable with am1
      hydroamination, the am5 hydroamination is energetically less favorable, and the
      am4 hydroamination is least favorable but could be realizable by elevating the
      temperature and pressure. We call experimental efforts to synthesize cat1-cat3 or
      similar new molecules on the basis of the design strategy.

PMID- 22585137
TI  - Adenosine A2A antagonists in Parkinson's disease: what's next?
AB  - Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder,
      affecting up to 10 million people worldwide. Current treatment primarily involves
      symptom management with dopaminergic replacement therapy. Levodopa remains the
      most effective oral treatment, although long-term use is associated with
      complications such as wearing off, dyskinesias, and on-off fluctuations. Non
      dopaminergic medications that improve PD symptoms and motor fluctuations are in
      demand. Adenosine A2A receptors are abundantly expressed within the basal ganglia
      and offer a unique target to modify abnormal striatal signaling associated with
      PD. Preclinical animal models have shown the ability of adenosine A2A receptor
      antagonists to improve PD motor symptoms, reduce motor fluctuations and
      dyskinesia, as well as protect against toxin-induced neuronal degeneration. Both
      istradefylline and preladenant have demonstrated moderate efficacy in reducing
      off time in PD patients with motor fluctuations. The safety and efficacy of this
      class of compounds continues to be defined and future studies should focus on non
      motor symptoms, dyskinesias, and neuroprotection.

PMID- 22585139
TI  - Hierarchical motif vectors for prediction of functional sites in amino acid
      sequences using quasi-supervised learning.
AB  - We propose hierarchical motif vectors to represent local amino acid sequence
      configurations for predicting the functional attributes of amino acid sites on a
      global scale in a quasi-supervised learning framework. The motif vectors are
      constructed via wavelet decomposition on the variations of physico-chemical amino
      acid properties along the sequences. We then formulate a prediction scheme for
      the functional attributes of amino acid sites in terms of the respective motif
      vectors using the quasi-supervised learning algorithm that carries out
      predictions for all sites in consideration using only the experimentally verified
      sites. We have carried out comparative performance evaluation of the proposed
      method on the prediction of N-glycosylation of 55,184 sites possessing the
      consensus N-glycosylation sequon identified over 15,104 human proteins, out of
      which only 1,939 were experimentally verified N-glycosylation sites. In the
      experiments, the proposed method achieved better predictive performance than the
      alternative strategies from the literature. In addition, the predicted N
      glycosylation sites showed good agreement with existing potential annotations,
      while the novel predictions belonged to proteins known to be modified by
      glycosylation.

PMID- 22585140
TI  - How little do we actually know? On the size of gene regulatory networks.
AB  - The National Center for Biotechnology Information (NCBI) recently announced the
      availability of whole genome sequences for more than 1,000 species. And the
      number of sequenced individual organisms is growing. Ongoing improvement of DNA
      sequencing technology will further contribute to this, enabling large-scale
      evolution and population genetics studies. However, the availability of sequence
      information is only the first step in understanding how cells survive, reproduce,
      and adjust their behavior. The genetic control behind organized development and
      adaptation of complex organisms still remains widely undetermined. One major
      molecular control mechanism is transcriptional gene regulation. The direct
      juxtaposition of the total number of sequenced species to the handful of model
      organisms with known regulations is surprising. Here, we investigate how little
      we even know about these model organisms. We aim to predict the sizes of the
      whole-organism regulatory networks of seven species. In particular, we provide
      statistical lower bounds for the expected number of regulations. For Escherichia
      coli we estimate at most 37 percent of the expected gene regulatory interactions
      to be already discovered, 24 percent for Bacillus subtilis, and <3% human,
      respectively. We conclude that even for our best researched model organisms we
      still lack substantial understanding of fundamental molecular control mechanisms,
      at least on a large scale.

PMID- 22585141
TI  - Qualitative reasoning for biological network inference from systematic
      perturbation experiments.
AB  - The systematic perturbation of the components of a biological system has been
      proven among the most informative experimental setups for the identification of
      causal relations between the components. In this paper, we present Systematic
      Perturbation-Qualitative Reasoning (SPQR), a novel Qualitative Reasoning approach
      to automate the interpretation of the results of systematic perturbation
      experiments. Our method is based on a qualitative abstraction of the experimental
      data: for each perturbation experiment, measured values of the observed variables
      are modeled as lower, equal or higher than the measurements in the wild type
      condition, when no perturbation is applied. The algorithm exploits a set of IF
      THEN rules to infer causal relations between the variables, analyzing the
      patterns of propagation of the perturbation signals through the biological
      network, and is specifically designed to minimize the rate of false positives
      among the inferred relations. Tested on both simulated and real perturbation
      data, SPQR indeed exhibits a significantly higher precision than the state of the
      art.

PMID- 22585142
TI  - A novel method to select informative SNPs and their application in genetic
      association studies.
AB  - The association studies between complex diseases and single nucleotide
      polymorphisms (SNPs) or haplotypes have recently received great attention.
      However, these studies are limited by the cost of genotyping all SNPs. Therefore,
      it is essential to find a small subset of tag SNPs representing the rest of the
      SNPs. The presence of linkage disequilibrium between tag SNPs and the disease
      variant (genotyped or not), may allow fine mapping study. In this paper, we
      combine a nearest-means classifier (NMC) and ant colony algorithm to select tags.
      Results show that our method (ACO/NMC) can get a similar prediction accuracy with
      method BPSO/SVM and is better than BPSO/STAMPA for small data sets. For large
      data sets, although the prediction accuracy of our method is lower than BPSO/SVM,
      ACO/NMC can reach a high accuracy (>99 percent) in a relatively short time. when
      the number of tags increases, the time complexity of NMC is nearly linear growth.
      To find out that the ability of tags to locate disease locus, we simulate a case
      control study and use two-locus haplotype analysis to quantitatively assess the
      power. The result showed that 20 percent of all SNPs selected by NMC have about
      10 percent higher power than random tags, on average.

PMID- 22585149
TI  - Q&A: Craig Thompson on research joys and jobs by Suzanne Rose.

PMID- 22585150
TI  - Jobs wanted: cancer research.

PMID- 22585151
TI  - Combinations go on trial.

PMID- 22585162
TI  - A role for ATM in hereditary pancreatic cancer.
AB  - The genetic risk factors that contribute to pancreatic cancers are largely
      unknown. A new next-generation sequencing study by Roberts and colleagues now
      adds ATM to the list of pancreatic ductal adenocarcinoma predisposition genes.

PMID- 22585163
TI  - Dissecting "PI3Kness": the complexity of personalized therapy for ovarian cancer.
AB  - Epithelial ovarian cancers exhibit marked heterogeneity and can be divided into
      low-grade type I and more prevalent high-grade type II lesions that differ in
      stage at diagnosis, rate of growth, and susceptibility to platinum-based
      chemotherapy. Activation of the phosphatidylinositol 3' kinase (PI3K) pathway
      occurs in a significant fraction of both types of ovarian cancer, driven
      predominantly by mutations in type I and amplification in type II. Available cell
      lines do not often reflect the genotype of type II ovarian cancers, but studies
      with cell lines driven by mutation suggest that blocking activated AKT is
      necessary, but not sufficient to inhibit cancer cell growth. Inhibition of
      multiple signaling pathways will likely be required to achieve effective
      personalized therapy for patients whose cancers exhibit "PI3Kness."

PMID- 22585164
TI  - The 14-3-3sigma tumor suppressor has multiple functions in ErbB2-induced breast
      cancer.
AB  - Ling and colleagues demonstrated that loss of the conditional 14-3-3sigma allele
      results in accelerated HER2/ERBB2-driven mammary tumorigenesis and metastasis.
      This study underscores the role of 14-3-3sigma as a potent tumor suppressor in
      ERBB2-driven tumor initiation and progression.

PMID- 22585165
TI  - Tackling formalin-fixed, paraffin-embedded tumor tissue with next-generation
      sequencing.
AB  - Most tumor samples available for clinical genotyping are formalin-fixed and
      paraffin-embedded (FFPE), but there has been relatively little published on the
      suitability of such samples for next-generation sequencing approaches. A new
      study by Wagle and colleagues shows that a combination of hybridization-capture
      and deep sequencing yields high-quality data from FFPE specimens.

PMID- 22585166
TI  - Exemestane for breast cancer prevention: a critical shift?
AB  - The Mammary Prevention 3 (MAP.3) placebo-controlled randomized trial in 4,560
      high-risk postmenopausal women showed a 65% reduction in invasive breast cancer
      with the use of exemestane at 35 months median follow-up. Few differences in
      adverse events were observed between the arms, suggesting a promising
      risk:benefit balance with exemestane for use in chemoprevention. Yet, the MAP.3
      design and implementation raise concerns regarding limited data maturity and not
      prospectively including key bone-related and other toxicities as study end
      points. Exemestane for prevention is juxtaposed against selective estrogen
      receptor modulators and the other aromatase inhibitors. Additional issues for
      prevention, including the influence of obesity, alternative dosing, and biomarker
      use in phase III trials, are addressed. SIGNIFICANCE: The recently completed
      MAP.3 trial of exemestane for breast cancer prevention offers a potential new
      standard for pharmaceutical risk reduction in high-risk postmenopausal women. In
      addition to describing key findings from the publication of MAP.3 and related
      trials, our review undertakes a detailed analysis of the strengths and weaknesses
      of MAP.3 as well as the implications for future prevention research.

PMID- 22585167
TI  - ATM mutations in patients with hereditary pancreatic cancer.
AB  - Pancreatic cancers are the fourth most-common cause of cancer-related deaths in
      the Western world, with >200,000 cases reported in 2010. Although up to 10% of
      these cases occur in familial patterns, the hereditary basis for predisposition
      in the vast majority of affected families is unknown. We used next-generation
      sequencing, including whole-genome and whole-exome analyses, and identified
      heterozygous, constitutional, ataxia telangiectasia mutated (ATM) gene mutations
      in 2 kindreds with familial pancreatic cancer. Mutations segregated with disease
      in both kindreds and tumor analysis demonstrated LOH of the wild-type allele. By
      using sequence analysis of an additional 166 familial pancreatic cancer probands,
      we identified 4 additional patients with deleterious mutations in the ATM gene,
      whereas we identified no deleterious mutations in 190 spouse controls (P =
      0.046). When we considered only the mostly severely affected families with 3 or
      more pancreatic cancer cases, 4 deleterious mutations were found in 87 families
      (P = 0.009). Our results indicate that inherited ATM mutations play an important
      role in familial pancreatic cancer predisposition. SIGNIFICANCE: The genes
      responsible for the majority of cases of familial pancreatic ductal
      adenocarcinoma are unknown. We here identify ATM as a predisposition gene for
      pancreatic ductal adenocarcinoma. Our results have important implications for the
      management of patients in affected families and illustrate the power of genome
      wide sequencing to identify the basis of familial cancer syndromes.

PMID- 22585168
TI  - Molecular ontogeny of donor-derived follicular lymphomas occurring after
      hematopoietic cell transplantation.
AB  - The relative timing of genetic alterations that contribute to follicular lymphoma
      remains unknown. We analyzed a donor-recipient pair who both developed grade 2/3A
      follicular lymphoma 7 years after allogeneic transplantation and donor lymphocyte
      infusions. Both patients harbored identical BCL2/IGH rearrangements also present
      in 1 in 2,000 cells in the donor lymphocyte infusion, and the same V(D)J
      rearrangement, which underwent somatic hypermutation both before and after clonal
      divergence. Exome sequencing of both follicular lymphomas identified 15 shared
      mutations, of which 14 (including alterations in EP300 and KLHL6) were recovered
      from the donor lymphocyte infusion by ultra-deep sequencing (average read
      coverage, 361,723), indicating acquisition at least 7 years before clinical
      presentation. Six additional mutations were present in only one follicular
      lymphoma and not the donor lymphocyte infusion, including an ARID1A premature
      stop, indicating later acquisition during clonal divergence. Thus, ultrasensitive
      sequencing can map clonal evolution within rare subpopulations during human
      lymphomagenesis in vivo. SIGNIFICANCE: For the first time, we define the
      molecular ontogeny of follicular lymphoma during clonal evolution in vivo. By
      using ultrasensitive mutation detection, we mapped the time-course of somatic
      alterations after passage of a malignant ancestor by hematopoietic cell
      transplantation.

PMID- 22585169
TI  - Loss of the 14-3-3sigma tumor suppressor is a critical event in ErbB2-mediated
      tumor progression.
AB  - 14-3-3sigma is a putative tumor suppressor involved in cell-cycle progression and
      epithelial polarity. We demonstrate that loss of one or both copies of the
      conditional 14-3-3sigma allele results in accelerated mammary and salivary
      tumorigenesis in mice expressing an activated erbB2 oncogene under the endogenous
      erbB2 promoter. Significantly, the majority of tumors bearing a single
      conditional 14-3-3sigma allele lose expression of the remaining 14-3-3sigma
      allele, which is associated with epigenetic methylation of the 14-3-3sigma locus.
      In addition to accelerated tumor onset, in a mouse mammary tumor virus-driven
      ErbB2 tumor model, loss of 14-3-3sigma results in enhanced metastatic phenotype
      that is correlated with loss of cellular junctions. Taken together, these results
      provide compelling evidence that 14-3-3sigma is a potent tumor suppressor
      involved in ErbB2-driven breast cancer initiation and metastasis. SIGNIFICANCE:
      14-3-3sigma has been identified as a normal mammary epithelial cell marker
      frequently downregulated during neoplastic development. Consistent with its
      potential role as a tumor suppressor, we demonstrate that targeted disruption of
      14-3-3sigma in a number of epithelial tissues can profoundly impact both the
      initiation and metastatic phases of ErbB2-mediated tumor progression through
      modulation of a number of distinct signaling networks.

PMID- 22585171
TI  - Modified stem cells create tumor-attacking T cells.

PMID- 22585170
TI  - High-throughput detection of actionable genomic alterations in clinical tumor
      samples by targeted, massively parallel sequencing.
AB  - Knowledge of "actionable" somatic genomic alterations present in each tumor
      (e.g., point mutations, small insertions/deletions, and copy-number alterations
      that direct therapeutic options) should facilitate individualized approaches to
      cancer treatment. However, clinical implementation of systematic genomic
      profiling has rarely been achieved beyond limited numbers of oncogene point
      mutations. To address this challenge, we utilized a targeted, massively parallel
      sequencing approach to detect tumor genomic alterations in formalin-fixed,
      paraffin-embedded (FFPE) tumor samples. Nearly 400-fold mean sequence coverage
      was achieved, and single-nucleotide sequence variants, small
      insertions/deletions, and chromosomal copynumber alterations were detected
      simultaneously with high accuracy compared with other methods in clinical use.
      Putatively actionable genomic alterations, including those that predict
      sensitivity or resistance to established and experimental therapies, were
      detected in each tumor sample tested. Thus, targeted deep sequencing of clinical
      tumor material may enable mutation-driven clinical trials and, ultimately,
      "personalized" cancer treatment. SIGNIFICANCE: Despite the rapid proliferation of
      targeted therapeutic agents, systematic methods to profile clinically relevant
      tumor genomic alterations remain underdeveloped. We describe a sequencingbased
      approach to identifying genomic alterations in FFPE tumor samples. These studies
      affirm the feasibility and clinical utility of targeted sequencing in the
      oncology arena and provide a foundation for genomics-based stratification of
      cancer patients.

PMID- 22585172
TI  - "Reversed" Krebs cycle can feed tumors.

PMID- 22585173
TI  - Mathematical model could aid biomarker validation.

PMID- 22585174
TI  - Dual HER2 blockade slows metastatic breast cancer.

PMID- 22585175
TI  - Biotech firms look for virtual success.

PMID- 22585178
TI  - Cancer Discovery at one year: the editors' interim analysis.

PMID- 22585180
TI  - Circadian disruption--a new direction for psycho-oncology research? A comment on
      Dedert et al.

PMID- 22585179
TI  - Group-based trajectory modeling of caregiver psychological distress over time.
AB  - BACKGROUND: Competing theories of adaptation and wear-and-tear describe
      psychological distress patterns among family caregivers. PURPOSE: This study
      seeks to characterize psychological distress patterns in family caregivers and
      identify predictors. METHODS: One hundred three caregivers of care recipients
      with primary malignant brain tumors were interviewed within 1, 4, 8, and 12
      months post-diagnosis regarding psychological distress; care recipients were
      interviewed regarding clinical/functional characteristics. Group-based trajectory
      modeling identified longitudinal distress patterns, and weighted
      logistic/multinomial regression models identified predictors of distress
      trajectories. RESULTS: Group-based trajectory modeling identified high-decreasing
      (51.1 % of caregivers) and consistently low (48.9 %) depressive symptom
      trajectories, high-decreasing (75.5 %) and low-decreasing (24.5 %) anxiety
      trajectories, and high (37.5 %), moderate (40.9 %), and low-decreasing (21.6 %)
      caregiver burden trajectories. High depressive symptoms were associated with high
      trajectories for both anxiety and burden, lower caregivers age, income, and
      social support, and lower care recipient functioning. CONCLUSIONS: Our data
      support the adaptation hypothesis; interventions should target those at risk for
      persistent distress.

PMID- 22585181
TI  - Specific binding structures of dendrimers on lipid bilayer membranes.
AB  - Dissipative particle dynamics simulations are used to study the specific binding
      structures of polyamidoamine (PAMAM) dendrimers on amphiphilic membranes and the
      permeation mechanisms. Mutually consistent coarse-grained (CG) models both for
      PAMAM dendrimers and for dimyristoylphosphatidylcholine (DMPC) lipid molecules
      are constructed. The PAMAM CG model describes correctly the conformational
      behavior of the dendrimers, and the DMPC CG model can properly give the surface
      tension of the amphiphilic membrane. A series of systematic simulations is
      performed to investigate the binding structures of the dendrimers on membranes
      with varied length of the hydrophobic tails of amphiphiles. The permeability of
      dendrimers across membranes is enhanced upon increasing the dendrimer size
      (generation). The length of the hydrophobic tails of amphiphiles in turn affects
      the dendrimer conformation, as well as the binding structure of the dendrimer
      membrane complexes. The negative curvature of the membrane formed in the
      dendrimer-membrane complexes is related to dendrimer concentration. Higher
      dendrimer concentration together with increased dendrimer generation is observed
      to enhance the permeability of dendrimers across the amphiphilic membranes.

PMID- 22585182
TI  - Prognostic significance of fragmented QRS in patients with non-ST elevation
      myocardial infarction: results of a 1-year, single-center follow-up.
AB  - OBJECTIVES: The aim of this study was to evaluate the predictive value of
      fragmented QRS (fQRS) among non-ST elevation acute coronary syndrome (ACS)
      patients. DESIGN: The fQRS on standard 12-lead ECGs in 179 patients (63% males,
      mean age 60.9 +/- 12.3 years) were analyzed. Cardiac events and cardiac mortality
      were regarded as two outcomes to determine whether fQRS was a clinical prognostic
      factor; its prognostic value was then assessed adjusting for other covariates.
      RESULTS: Cardiac mortality (18 (17.0%) vs. 4 (5.5%)) and major cardiac event rate
      (46 (43.4%) vs. 22 (30.1%)) were higher in the fQRS group compared with the non
      fQRS group during a mean follow-up of 12 months. A Kaplan-Meier survival analysis
      revealed significantly lower event-free survival for cardiac events (p = 0.030)
      and cardiac mortality (p = 0.020). Multivariate Cox regression analysis revealed
      that significant fQRS was an independent significant predictor for cardiac events
      and cardiac mortality. CONCLUSION: These results indicate that the occurrence of
      fQRS in the ECG is a powerful predictor of decreased survival in NSTEMI. The
      prognostic importance of fQRS was incremental to clinical and conventional
      factors.

PMID- 22585183
TI  - Target concentration intervention in oncology:  where are we at?
AB  - Therapeutic drug monitoring (TDM) and more recently target concentration
      intervention (TCI) have been widely used in clinical practice for the
      optimization of drug treatment. TDM and TCI have been applied most frequently in
      the cardiovascular, respiratory, neurology, and infectious disease areas because
      the medications used here have both narrow therapeutic indices and a clear
      relationship between concentration and effect. However, apart from drugs such as
      methotrexate and 5-fluorouracil, the clinical application of TDM/TCI in oncology
      is minimal. An important reason for this is that a therapeutic index for most
      anticancer agents has not been established. However, in the last 20 years,
      relationships between plasma drug concentrations and clinical outcome have been
      defined for various chemotherapeutic agents. Defining concentration-effect
      relationships is also complicated by the fact that cancer is almost always
      treated with multiple drugs given in combination making the precise definition of
      the pharmacodynamics of individual agents difficult. The increase in patients
      with obesity and also those underweight adds to the complexity of effective
      oncology treatment. This review describes some of the evidence that supports the
      use of TDM/TCI in oncology. It is proposed that as more patients previously
      ineligible for chemotherapy become eligible, TDM/TCI may play a critical role in
      optimizing chemotherapy outcomes. However, pharmacokinetic-pharmacodynamic
      research to investigate both therapeutic benefit and feasibility in daily
      clinical practice is required.

PMID- 22585184
TI  - New sampling strategy using a Bayesian approach to assess iohexol clearance in
      kidney transplant recipients.
AB  - BACKGROUND: Glomerular filtration rate (GFR) measurement is a major issue in
      kidney transplant recipients for clinicians. GFR can be determined by estimating
      the plasma clearance of iohexol, a nonradiolabeled compound. For practical and
      convenient application for patients and caregivers, it is important that a
      minimal number of samples are drawn. The aim of this study was to develop and
      validate a Bayesian model with fewer samples for reliable prediction of GFR in
      kidney transplant recipients. METHODS: Iohexol plasma concentration-time curves
      from 95 patients were divided into an index (n = 63) and a validation set (n =
      32). Samples (n = 4-6 per patient) were obtained during the elimination phase,
      that is, between 120 and 270 minutes. Individual reference values of iohexol
      clearance (CL(iohexol)) were calculated from k (elimination slope) and V (volume
      of distribution from intercept). Individual CL(iohexol) values were then
      introduced into the Brochner-Mortensen equation to obtain the GFR (reference
      value). A population pharmacokinetic model was developed from the index set and
      validated using standard methods. For the validation set, we tested various
      combinations of 1, 2, or 3 sampling time to estimate CL(iohexol). According to
      the different combinations tested, a maximum a posteriori Bayesian estimation of
      CL(iohexol) was obtained from population parameters. Individual estimates of GFR
      were compared with individual reference values through analysis of bias and
      precision. A capability analysis allowed us to determine the best sampling
      strategy for Bayesian estimation. RESULTS: A 1-compartment model best described
      our data. Covariate analysis showed that uremia, serum creatinine, and age were
      significantly associated with k(e), and weight with V. The strategy, including
      samples drawn at 120 and 270 minutes, allowed accurate prediction of GFR (mean
      bias: -3.71%, mean imprecision: 7.77%). With this strategy, about 20% of
      individual predictions were outside the bounds of acceptance set at +/- 10%, and
      about 6% if the bounds of acceptance were set at +/- 15%. CONCLUSIONS: This
      Bayesian approach can help to reduce the number of samples required to calculate
      GFR using Brochner-Mortensen formula with good accuracy.

PMID- 22585187
TI  - What is vitamin D insufficiency? And does it matter?
AB  - The term nutrient "insufficiency," as commonly used, refers to a nutritional
      status intermediate between classical, severe deficiency, and full normal. As
      both "deficiency" and "insufficiency" are causes of dysfunction and disease,
      there is no biological basis for a distinction between them. What is important to
      note is that, in the case of vitamin D, the preponderance of the evidence
      indicates that there is real, preventable disease in the range of vitamin D
      status values now labeled "insufficient."

PMID- 22585185
TI  - The role of decreased levels of Niemann-Pick C1 intracellular cholesterol
      transport on obesity is reversed in the C57BL/6J, metabolic syndrome mouse
      strain: a metabolic or an inflammatory effect?
AB  - We have previously shown that decreased dosage of Niemann-Pick C1 (Npc1) protein,
      caused by heterozygosity at the null mutation, Npc1 (nih), locus, causes altered
      lipid metabolism in mice. When studied on the "lean" BALB/cJ genetic background,
      the decreased protein was associated with no weight changes in either males or
      females when on a regular diet but increased weights and adiposity when on a high
      fat diet Jelinek et al. (Obesity 18: 1457-1459, 2010, Gene 491:128-134, 2012).
      When the heterozygotes were studied on a mixed C57BL/6J, BALB/cJ background,
      increased weight and adiposity were also found on a regular diet (sexes pooled
      Jelinek et al. [Hum Molec Genet 20:312-321, 2011]). We find somewhat different
      results when the hypomorphic Npc1 mutation, Npc1 (nmf164), is studied on a pure
      C57BL/6J, "metabolic syndrome" genetic background with male, but not female,
      heterozygotes having lower weights on the regular diet. The result does not seem
      to be due to the difference in the two mutations as heterozygous Npc1 (nmf164)
      mice on the BALB/cJ background acted like the null mutant heterozygotes. Studies
      of glucose tolerance, liver enzymes, liver triglycerides and fat deposition, and
      adipose tissue caveolin 1 levels did not disclose reasons for these differing
      results.

PMID- 22585186
TI  - Attitudes and practices among internists concerning genetic testing.
AB  - Many questions remain concerning whether, when, and how physicians order genetic
      tests, and what factors are involved in their decisions. We surveyed 220
      internists from two academic medical centers about their utilization of genetic
      testing. Rates of genetic utilizations varied widely by disease. Respondents were
      most likely to have ordered tests for Factor V Leiden (16.8 %), followed by
      Breast/Ovarian Cancer (15.0 %). In the past 6 months, 65 % had counseled patients
      on genetic issues, 44 % had ordered genetic tests, 38.5 % had referred patients
      to a genetic counselor or geneticist, and 27.5 % had received ads from commercial
      labs for genetic testing. Only 4.5 % had tried to hide or disguise genetic
      information, and <2 % have had patients report genetic discrimination. Only 53.4
      % knew of a geneticist/genetic counselor to whom to refer patients. Most rated
      their knowledge as very/somewhat poor concerning genetics (73.7 %) and guidelines
      for genetic testing (87.1 %). Most felt needs for more training on when to order
      tests (79 %), and how to counsel patients (82 %), interpret results (77.3 %), and
      maintain privacy (80.6 %). Physicians were more likely to have ordered a genetic
      test if patients inquired about genetic testing (p < .001), and if physicians had
      a geneticist/genetic counselor to whom to refer patients (p < .002), had referred
      patients to a geneticist/genetic counselor in the past 6 months, had more comfort
      counseling patients about testing (p < .019), counseled patients about genetics,
      larger practices (p < .032), fewer African-American patients (p < .027), and
      patients who had reported genetic discrimination (p < .044). In a multiple
      logistic regression, ordering a genetic test was associated with patients
      inquiring about testing, having referred patients to a geneticist/genetic
      counselor and knowing how to order tests. These data suggest that physicians
      recognize their knowledge deficits, and are interested in training. These
      findings have important implications for future medical practice, research, and
      education.

PMID- 22585188
TI  - Synthesis and antibacterial activity of novel neamine derivatives: preponderant
      role of the substituent position on the neamine core.
AB  - A series of neamine derivatives were prepared from the cyclic carbonate and
      sulfate of 1,3,2',6'-tetraazido-3',4',-di-O-acetylneamine. Ring opening reactions
      with diversely substituted amines result in the formation of the corresponding
      carbamates or sulfonic acids with good overall yields. The antibacterial
      activities of the synthesized products against E. coli (DH5alpha) and S. aureus
      (RN4220) were evaluated. With isolated single regioisomers, the preponderant
      effect of the 5-positions of the carbamate substituent on the neamine core was
      demonstrated.

PMID- 22585189
TI  - Psychometric evaluation of the Danish and Swedish Satisfaction with Life Scale in
      first episode psychosis patients.
AB  - PURPOSE: To psychometrically evaluate the Satisfaction with Life Scale in two
      cohorts of first-episode psychosis patients in the Danish National Schizophrenia
      Project and in the Swedish Parachute Project. METHOD: Four properties of the
      Satisfaction with Life Scale were examined in the Danish cohort (explorative
      investigation) and then confirmed in the Swedish cohort: (1) the factor
      structure; (2) correlations between subscales; (3) internal consistencies of
      subscales; and (4) main tendencies (arithmetic means) and variations (standard
      deviations) of subscales. The relations between the Satisfaction with Life Scale
      and various life conditions were investigated in the Swedish cohort. RESULTS: For
      both samples, the analysis indicated that the obtained four-dimensional 11-item
      scale had satisfactory properties. Moderately high scores were obtained in the
      four subscales: "living," "social relationships," "self and present life" and
      "work." They correlated positively with each other, the internal consistencies of
      the subscales were acceptable and the means for the subscales indicated no
      apparent floor or ceiling effects. The four dimensions obtained seem relevant and
      presented good face validity. The dimensions were confirmed in the Swedish
      sample. CONCLUSION: The Satisfaction with Life Scale shows satisfactory
      psychometric properties and seems valid and useful among first-episode psychosis
      patients.

PMID- 22585191
TI  - Rationing based on 'procedures of limited clinical effectiveness': what are the
      risks?

PMID- 22585190
TI  - Predicting quality of life in pediatric asthma: the role of emotional competence
      and personality.
AB  - PURPOSE: The present study examined the predictive value of emotional competence
      and the five-factor model of personality on the quality of life of children with
      asthma. METHODS: Participants were 90 children (M age = 11.73, SD = 2.60) having
      controlled and partly controlled asthma, undergoing everyday treatment. Children
      filled in questionnaires assessing emotional competence and quality of life.
      Parents completed questionnaires assessing the personality of their child.
      RESULTS: Results showed that two emotional competences, bodily awareness and
      verbal sharing of emotions, were related to the quality of life of children with
      asthma. Moreover, one personality trait, benevolence, was associated with
      children's quality of life. Regression analyses showed that the predictive value
      of these three dimensions remained significant over and above asthma control and
      socio-demographic variables frequently associated with the quality of life of
      children with asthma (age, gender, and educational level of parents).
      CONCLUSIONS: These findings emphasize the importance of alerting the clinician
      who works with children with asthma to observe and assess the child's expression
      of emotions, attention to bodily sensations, and benevolence.

PMID- 22585192
TI  - Multidisciplinary team working: the emperor without clothes?

PMID- 22585194
TI  - Management of surgical conditions  of the wrist.

PMID- 22585195
TI  - Carpal tunnel syndrome.

PMID- 22585196
TI  - Congenital hand anomalies  and reconstruction.

PMID- 22585197
TI  - Fibromyalgia syndrome and depression: common pathways.

PMID- 22585198
TI  - Adult urinary tract infection.

PMID- 22585199
TI  - The early days of the flexible gastroscope  in the UK.

PMID- 22585200
TI  - Interscalene block as a precipitant  of respiratory dysfunction.

PMID- 22585201
TI  - Percutaneous repair of an aortopulmonary fistula using platinum coils.

PMID- 22585202
TI  - Intractable pain from trigeminal neuralgia.

PMID- 22585204
TI  - Lactic acidosis in a diabetic patient treated with metformin undergoing hepatic
      resection.

PMID- 22585203
TI  - TB or not TB: a diagnostic dilemma.

PMID- 22585205
TI  - Role of computed tomography in elderly patients with small bowel obstruction.

PMID- 22585206
TI  - Testosterone-induced erythrocytosis affecting haematocrit prediction of fluid
      responsiveness.

PMID- 22585207
TI  - Five steps to smarter saving.

PMID- 22585209
TI  - Stress ulcer prophylaxis: friend or foe?

PMID- 22585210
TI  - Central leptin replacement enhances chemorespiratory responses in leptin
      deficient mice independent of changes in body weight.
AB  - Previous studies showed that leptin-deficient (ob/ob) mice develop obesity and
      impaired ventilatory responses to CO(2) (V(E) - CO(2)). In this study, we
      examined if leptin replacement improves chemorespiratory responses to hypercapnia
      (7 % CO(2)) in ob/ob mice and if these effects were due to changes in body weight
      or to the direct effects of leptin in the central nervous system (CNS). V(E) -
      CO(2) was measured via plethysmography in obese leptin-deficient- (ob/ob) and
      wild-type- (WT) mice before and after leptin (10 MUg/2 MUl day) or vehicle
      (phosphate buffer solution) were microinjected into the fourth ventricle for four
      consecutive days. Although baseline V(E) was similar between groups, obese ob/ob
      mice exhibited attenuated V(E) - CO(2) compared to WT mice (134 +/- 9 versus 196
      +/- 10 ml min(-1)). Fourth ventricle leptin treatment in obese ob/ob mice
      significantly improved V(E) - CO(2) (from 131 +/- 15 to 197 +/- 10 ml min(-1)) by
      increasing tidal volume (from 0.38 +/- 0.03 to 0.55 +/- 0.02 ml, vehicle and
      leptin, respectively). Subcutaneous leptin administration at the same dose
      administered centrally did not change V(E) - CO(2) in ob/ob mice. Central leptin
      treatment in WT had no effect on V(E) - CO(2). Since the fourth ventricle leptin
      treatment decreased body weight in ob/ob mice, we also examined V(E) - CO(2) in
      lean pair-weighted ob/ob mice and found it to be impaired compared to WT mice.
      Thus, leptin deficiency, rather than obesity, is the main cause of impaired V(E) 
      CO(2) in ob/ob mice and leptin appears to play an important role in regulating
      chemorespiratory response by its direct actions on the CNS.

PMID- 22585211
TI  - Efficacy of daptomycin-cloxacillin combination in experimental foreign-body
      infection due to methicillin-resistant Staphylococcus aureus.
AB  - Despite the use of daptomycin alone at high doses (greater than 6 mg/kg of body
      weight/day) against difficult-to-treat infections, clinical failures and
      resistance appeared. Recently, the combination daptomycin-cloxacillin showed
      enhanced efficacy in clearing bacteremia caused by methicillin-resistant
      Staphylococcus aureus (MRSA). The aim of this study was to evaluate the efficacy
      of daptomycin at usual and high doses (equivalent to 6 and 10 mg/kg/day in
      humans, respectively) in combination with cloxacillin in a rat tissue cage
      infection model by MRSA and to compare its efficacy to that of daptomycin
      rifampin. We used MRSA strain ATCC BAA-39. In the log- and stationary-phase kill
      curves, daptomycin-cloxacillin improved the bactericidal activity of daptomycin,
      especially in log phase. For in vivo studies, therapy was administered
      intraperitoneally for 7 days with daptomycin at 100 mg/kg/day and 45/mg/kg/day
      (daptomycin 100 and daptomycin 45), daptomycin 100-cloxacillin at 200 mg/kg/12 h,
      daptomycin 45-cloxacillin, and daptomycin 100-rifampin at 25 mg/kg/12 h.
      Daptomycin-rifampin was the best therapy (P < 0.05). Daptomycin 45 was the least
      effective treatment and did not protect against the emergence of resistant
      strains. There were no differences between the two dosages of daptomycin plus
      cloxacillin in any situation, and both protected against resistance. The overall
      effect of the addition of cloxacillin to daptomycin was a significantly greater
      cure rate (against adhered bacteria) than that for daptomycin alone. In
      conclusion, daptomycin-cloxacillin enhanced modestly the in vivo efficacy of
      daptomycin alone against foreign-body infection by MRSA and was less effective
      than daptomycin plus rifampin. The benefits of adding cloxacillin to daptomycin
      should be especially evaluated against infections by rifampin-resistant MRSA and
      for protection against the emergence of daptomycin nonsusceptibility.

PMID- 22585212
TI  - Optimal dosing of miltefosine in children and adults with visceral leishmaniasis.
AB  - Only anecdotal data are available on the pharmacokinetics (PK) of miltefosine in
      children suffering from visceral leishmaniasis (VL). While failure rates were
      higher in children with VL, steady-state concentrations appeared lower than those
      seen with adults. We hypothesized that the current linear dosage (in milligrams
      per kilogram of body weight) is too low for children and that a new dosing
      algorithm based on an appropriate body size model would result in an optimal
      exposure. A population PK analysis was performed on three historic pooled data
      sets, including Indian children, Indian adults, and European adults. Linear and
      allometric scaling of PK parameters by either body weight or fat-free mass (FFM)
      was evaluated for body size models. Based on the developed PK model, a dosing
      algorithm for miltefosine in children and adults was proposed and evaluated in
      silico. The population PK model employing allometric scaling fitted best to the
      pooled miltefosine data. Allometric scaling by FFM reduced between-subject
      variability, e.g., for drug clearance, from 49.6% to 32.1%. A new allometric
      miltefosine dosing algorithm was proposed. Exposure to miltefosine was lower in
      children than adults receiving 2.5 mg/kg/day: a C(max) of 18.8 MUg/ml was reached
      by 90% of adults and 66.7% of children. The allometric daily dose resulted in
      similar levels of exposure to miltefosine for adults and children. The use of a
      new allometric dosing algorithm for miltefosine in VL patients results in optimal
      exposure to miltefosine in both adults and children and might improve clinical
      outcome in children.

PMID- 22585213
TI  - An outbreak of Mycoplasma pneumoniae caused by a macrolide-resistant isolate in a
      nursery school in China.
AB  - Eighteen out of 45 children were reported to have a respiratory illness during an
      outbreak at a temporary dormitory in a nursery school in China in 2011. To study
      the outbreak and to determine the risk factors for infection, an epidemiological
      investigation was performed. A standardized questionnaire was completed for a
      total of 45 children with the help of their guardians and parents. In addition,
      acute- and convalescent-phase serum samples and throat swabs from the children
      were taken for laboratory diagnosis. The diagnosis of a Mycoplasma-like illness
      was based on the following clinical criteria. The criteria were onset of illness
      after 31 May 2011, characterized by a cough, fever(>37.5  degrees C), or at least
      3 of the following symptoms: fever, sore throat, cough or expectoration, and
      runny or stuffy nose. PCR-restriction fragment length polymorphism (PCR-RFLP),
      determination of MICs, and sequencing were performed to determine the genotype,
      antibiotic resistance, and sequence polymorphisms of the isolated strains,
      respectively. The paired sera revealed that 15 patients were infected with
      Mycoplasma pneumoniae. Epidemiology confirmed that this was a point source
      outbreak, characterized by a short incubation period, a high secondary attack
      rate, and a long period of hospitalization. PCR-RFLP analysis revealed that the
      12 isolated strains of M. pneumoniae shared the same subtype P1 gene, and 23S
      rRNA sequence analysis showed that these strains harbored two macrolide-resistant
      gene-related point mutations at position 2063 and 2617. In this outbreak, the
      major risk factor was the distance between the bed of the first patient and the
      beds of close contacts (beds less than three meters apart). The strains isolated
      in this study were found to harbor two point mutations conferring macrolide
      resistance, indicating the importance of pathogen and drug resistance
      surveillance systems.

PMID- 22585214
TI  - In vitro activity of TP-271 against Mycobacterium abscessus, Mycobacterium
      fortuitum, and Nocardia species.
AB  - The in vitro activities of TP-271, a novel fluorocycline antimicrobial, against
      22 isolates of Mycobacterium abscessus, 22 isolates of Mycobacterium fortuitum,
      and 19 isolates of Nocardia spp. were studied by a microtiter broth dilution
      method. The MIC(90)s for M. abscessus, M. fortuitum, and Nocardia spp. were 0.5
      MUg/ml, 0.03 MUg/ml, and 8 MUg/ml, respectively. TP-271 was significantly more
      active than the respective control drug in virtually all tests.

PMID- 22585216
TI  - Pharmacokinetics of caspofungin in two patients with burn injuries.

PMID- 22585215
TI  - The cyclophilin inhibitor SCY-635 disrupts hepatitis C virus NS5A-cyclophilin A
      complexes.
AB  - The nonimmunosuppressive cyclophilin (Cyp) inhibitor SCY-635 blocks hepatitis C
      virus (HCV) replication both in vitro and in vivo and represents a novel potent
      anti-HCV agent. However, its mechanism of action remains to be fully elucidated.
      A growing body of evidence suggests that cyclophilin A (CypA) is absolutely
      necessary for HCV replication and that the HCV nonstructural 5A (NS5A) protein
      serves as a main viral ligand for CypA. In this study, we examined the effect of
      SCY-635 on HCV replication. Specifically, we asked whether SCY-635 blocks HCV
      replication by targeting CypA-NS5A interactions. We also investigated the
      possibility that HCV can escape SCY-635 selection pressure and whether this
      resistance influences either CypA-NS5A interactions or the dependence of HCV on
      CypA. We found not only that SCY-635 efficiently inhibits HCV replication, but it
      is sufficient alone to clear HCV replicon-containing cells. We found that SCY-635
      prevents CypA-NS5A interactions in a dose-dependent manner. SCY-635 prevents the
      contact between CypA and NS5A derived from genotypes 1 to 3. Together, these data
      suggest that NS5A-CypA interactions control HCV replication and that SCY-635
      blocks viral replication by preventing the formation of these complexes. We also
      found that NS5A mutant proteins found in SCY-635-resistant HCV replicons behave
      similarly to wild-type NS5A in terms of both CypA binding and SCY-635-mediated
      dissociation and inhibition of CypA binding. However, the NS5A mutations found in
      SCY-635-resistant HCV replicons rescued viral replication in CypA-knockdown
      cells, suggesting that the NS5A mutations, which arose in vitro under SCY-635
      selection, do not alter the binding affinity of CypA for NS5A. These specific
      mutations in NS5A eliminate the dependence of HCV RNA replication on the
      expression of host CypA.

PMID- 22585217
TI  - 2-alkylaminoethyl-1,1-bisphosphonic acids are potent inhibitors of the enzymatic
      activity of Trypanosoma cruzi squalene synthase.
AB  - As part of our efforts aimed at searching for new antiparasitic agents, the
      effect of representative 2-alkylaminoethyl-1,1-bisphosphonic acids on Trypanosoma
      cruzi squalene synthase (TcSQS) was investigated. These compounds had proven to
      be potent inhibitors of T. cruzi. This cellular activity had been associated with
      an inhibition of the enzymatic activity of T. cruzi farnesyl diphosphate
      synthase. 2-Alkylaminoethyl-1,1-bisphosphonic acids appear to have a dual action,
      since they also inhibit TcSQS at the nanomolar range.

PMID- 22585218
TI  - Plasma concentrations of posaconazole administered via nasogastric tube in
      patients in a surgical intensive care unit.
AB  - Abdominal surgery may affect intestinal absorption and the resulting levels of
      posaconazole in the blood. We measured plasma posaconazole levels in surgical
      intensive care unit (SICU) patients and tried to develop a predictive population
      pharmacokinetics model. A total of 270 samples from 15 patients receiving
      posaconazole via nasogastric tube were measured by high-performance liquid
      chromatography (HPLC). SICU patients showed lower plasma drug concentrations, a
      higher apparent clearance, and a higher volume of distribution than those in
      hematology patients, possibly due to poor absorption.

PMID- 22585219
TI  - Population pharmacokinetics of extended-infusion piperacillin-tazobactam in
      hospitalized patients with nosocomial infections.
AB  - While extended infusions of piperacillin-tazobactam (TZP) are increasingly used
      in practice, the effect of infusion on the pharmacokinetic (PK) profile of TZP
      has not been widely assessed. To assess its effect on the pharmacokinetic profile
      of TZP, seven serum samples were collected from 11 hospitalized patients who
      received 3.375 g TZP intravenously for 4 h every 8 h. Population pharmacokinetic
      models were fit to the PK data utilizing first-order, Michaelis-Menten (MM), and
      parallel first-order/MM clearance. A population PK model with first-order
      clearance was fit to the tazobactam PK data. Monte Carlo simulations (MCSs) were
      used to determine the most effective administration schedule to ensure that free
      piperacillin concentrations were above the MIC for at least 50% of the dosing
      interval (50% fT>MIC) and to quantify the extent of the nonlinear clearance. The
      model incorporating parallel linear/MM clearance best fit the piperacillin PK
      data. The MCSs demonstrated that approximately 50% of the administered
      piperacillin is cleared by the nonlinear clearance mechanism. The results of the
      MCSs also revealed that more intensive TZP extended infusion dosing schemes
      (3.375 to 4.5 g intravenously [3-h infusion] every 6 h) than those commonly used
      in clinical practice were needed to maximize the 50% fT>MIC for MICs of >=8
      mg/liter. This study suggests that extended infusion of TZP is the most effective
      method of administration for patients with nosocomial infections. Due to the
      hyperclearance nature of the hospitalized patient populations studied, more
      intensive TZP dosing regimens may be needed to maximize fT>MIC in certain
      hospitalized populations.

PMID- 22585220
TI  - Combination antimicrobial susceptibility testing of multidrug-resistant
      Stenotrophomonas maltophilia from cystic fibrosis patients.
AB  - Stenotrophomonas maltophilia is increasingly being isolated from the respiratory
      tract of individuals with cystic fibrosis, and, because of its multidrug
      resistant nature, the selection of suitable treatment regimens can be
      problematical. Etest methodology was used to facilitate MIC and antimicrobial
      combination testing on 80 isolates of S. maltophilia cultured from the
      respiratory tract of Scottish individuals with cystic fibrosis between 2001 and
      2010. The overall rate of susceptibility for the 1,410 MIC tests was 23.1%, and
      resistance was 68.9%. The most active antimicrobials were minocycline, co
      trimoxazole, and doxycycline, with 92.4%, 87.3%, and 58.8% of isolates being
      susceptible, respectively. Of the 517 combinations, 13.2% were synergistic, with
      the most synergistic being ticarcillin/clavulanate plus aztreonam (91.7%
      synergistic), ticarcillin/clavulanate plus colistin (40%), and
      ticarcillin/clavulanate plus levofloxacin (19.4%). Colistin plus tobramycin was
      the only antagonistic combination (0.2%). By the median susceptible breakpoint
      index, the most active combinations were minocycline plus co-trimoxazole (median
      index, 20), minocycline plus piperacillin-tazobactam (median, 20), and co
      trimoxazole plus ceftazidime (median, 16.5). The increasing problem of multidrug
      resistance in organisms recovered from the respiratory tracts of individuals with
      cystic fibrosis is not going to go away. Current susceptibility testing methods
      do not address the slow-growing organisms associated with chronic infection, and
      interpretive standards are based on achievable blood levels of antimicrobials.
      Addressing these issues specifically for organisms recovered from the respiratory
      tracts of individuals with cystic fibrosis should lead to better therapeutic
      outcomes and improved wellbeing of individuals with cystic fibrosis.

PMID- 22585221
TI  - Mechanistic assessment of DNA ligase as an antibacterial target in Staphylococcus
      aureus.
AB  - We report the use of a known pyridochromanone inhibitor with antibacterial
      activity to assess the validity of NAD(+)-dependent DNA ligase (LigA) as an
      antibacterial target in Staphylococcus aureus. Potent inhibition of purified LigA
      was demonstrated in a DNA ligation assay (inhibition constant [K(i)] = 4.0 nM)
      and in a DNA-independent enzyme adenylation assay using full-length LigA (50%
      inhibitory concentration [IC(50)] = 28 nM) or its isolated adenylation domain
      (IC(50) = 36 nM). Antistaphylococcal activity was confirmed against methicillin
      susceptible and -resistant S. aureus (MSSA and MRSA) strains (MIC = 1.0 MUg/ml).
      Analysis of spontaneous resistance potential revealed a high frequency of
      emergence (4 * 10(-7)) of high-level resistant mutants (MIC > 64) with associated
      ligA lesions. There were no observable effects on growth rate in these mutants.
      Of 22 sequenced clones, 3 encoded point substitutions within the catalytic
      adenylation domain and 19 in the downstream oligonucleotide-binding (OB) fold and
      helix-hairpin-helix (HhH) domains. In vitro characterization of the enzymatic
      properties of four selected mutants revealed distinct signatures underlying their
      resistance to inhibition. The infrequent adenylation domain mutations altered the
      kinetics of adenylation and probably elicited resistance directly. In contrast,
      the highly represented OB fold domain mutations demonstrated a generalized
      resistance mechanism in which covalent LigA activation proceeds normally and yet
      the parameters of downstream ligation steps are altered. A resulting decrease in
      substrate K(m) and a consequent increase in substrate occupancy render LigA
      resistant to competitive inhibition. We conclude that the observed tolerance of
      staphylococcal cells to such hypomorphic mutations probably invalidates LigA as a
      viable target for antistaphylococcal chemotherapy.

PMID- 22585222
TI  - In vitro activities of LTX-109, a synthetic antimicrobial peptide, against
      methicillin-resistant, vancomycin-intermediate, vancomycin-resistant, daptomycin
      nonsusceptible, and linezolid-nonsusceptible Staphylococcus aureus.
AB  - LTX-109 and eight other antimicrobial agents were evaluated against 155
      methicillin-resistant Staphylococcus aureus (MRSA) isolates, including strains
      resistant to vancomycin and strains with decreased susceptibility to daptomycin
      and linezolid, by microdilution tests to determine MICs. Time-kill assays were
      performed against representative MRSA, vancomycin-intermediate S. aureus (VISA),
      and vancomycin-resistant S. aureus (VRSA) isolates. LTX-109 demonstrated a MIC
      range of 2 to 4 MUg/ml and dose-dependent rapid bactericidal activity against S.
      aureus. This activity was not influenced by resistance to other
      antistaphylococcal agents.

PMID- 22585223
TI  - Moxifloxacin population pharmacokinetics in patients with pulmonary tuberculosis
      and the effect of intermittent high-dose rifapentine.
AB  - We described the population pharmacokinetics of moxifloxacin and the effect of
      high-dose intermittent rifapentine in patients with pulmonary tuberculosis who
      were randomized to a continuation-phase regimen of 400 mg moxifloxacin and 900 mg
      rifapentine twice weekly or 400 mg moxifloxacin and 1,200 mg rifapentine once
      weekly. A two-compartment model with transit absorption best described
      moxifloxacin pharmacokinetics. Although rifapentine increased the clearance of
      moxifloxacin by 8% during antituberculosis treatment compared to that after
      treatment completion without rifapentine, it did not result in a clinically
      significant change in moxifloxacin exposure.

PMID- 22585224
TI  - Pharmacokinetics of tulathromycin in healthy and neutropenic mice challenged
      intranasally with lipopolysaccharide from Escherichia coli.
AB  - Tulathromycin represents the first member of a novel subclass of macrolides,
      known as triamilides, approved to treat bovine and swine respiratory disease. The
      objectives of the present study were to assess the concentration-versus-time
      profile of tulathromycin in the plasma and lung tissue of healthy and neutropenic
      mice challenged intranasally with lipopolysaccharide (LPS) from Escherichia coli
      O111:B4. BALB/c mice were randomly allocated into four groups of 40 mice each:
      groups T-28 (tulathromycin at 28 mg/kg of body weight), T-7, T7-LPS, and T7-LPS
      CP (cyclophosphamide). Mice in group T-28 were treated with tulathromycin at 28
      mg/kg subcutaneously (s.c.) (time 0 h). The rest of the mice were treated with
      tulathromycin at 7 mg/kg s.c. (time 0 h). Animals in dose groups T-7-LPS and T7
      LPS-CP received a single dose of E. coli LPS intranasally at -7 h. Mice in group
      T7-LPS-CP were also rendered neutropenic with cyclophosphamide (150 mg/kg
      intraperitoneally) prior to the administration of tulathromycin. Blood and lung
      tissue samples were obtained from 5 mice from each dose group at each sampling
      time over 144 h after the administration of tulathromycin. There were not
      statistical differences in lung tissue concentrations among groups T-7, T-7-LPS,
      and T7-LPS-CP. For all dose groups, the distribution of tulathromycin in the
      lungs was rapid and persisted at relatively high levels during 6 days
      postadministration. The concentration-versus-time profile of tulathromycin in
      lung tissue was not influenced by the intranasal administration of E. coli LPS.
      The results suggest that in mice, neutrophils may not have a positive influence
      on tulathromycin accumulation in lung tissue when the drug is administered during
      either a neutrophilic or a neutropenic state.

PMID- 22585225
TI  - Prevalence of blaZ gene types and the inoculum effect with cefazolin among
      bloodstream isolates of methicillin-susceptible Staphylococcus aureus.
AB  - We sought to define the prevalence of blaZ gene types and the inoculum effect to
      cefazolin among methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream
      infections. The blaZ gene was present in 142/185 (77%) isolates. A total of 50
      (27%) isolates had a >=4-fold increase in the cefazolin MIC from a standard to a
      high inoculum, and 8 (4%) demonstrated a nonsusceptible cefazolin MIC, all type A
      blaZ strains. The efficacy of cefazolin in the presence of the inoculum effect
      requires further study.

PMID- 22585226
TI  - Effects of antimicrobial peptides on methanogenic archaea.
AB  - As members of the indigenous human microbiota found on several mucosal tissues,
      Methanobrevibacter smithii and Methanosphaera stadtmanae are exposed to the
      effects of antimicrobial peptides (AMPs) secreted by these epithelia. Although
      antimicrobial and molecular effects of AMPs on bacteria are well described, data
      for archaea are not available yet. Besides, it is not clear whether AMPs affect
      them as the archaeal cell envelope differs profoundly in terms of chemical
      composition and structure from that of bacteria. The effects of different
      synthetic AMPs on growth of M. smithii, M. stadtmanae, and Methanosarcina mazei
      were tested using a microtiter plate assay adapted to their anaerobic growth
      requirements. All three tested methanoarchaea were highly sensitive against
      derivatives of human cathelicidin, of porcine lysin, and a synthetic
      antilipopolysaccharide peptide (Lpep); however, sensitivities differed markedly
      among the methanoarchaeal strains. The potent AMP concentrations affecting growth
      were below 10 MUM, whereas growth of Escherichia coli WBB01 was not affected at
      peptide concentrations up to 10 MUM under the same anaerobic growth conditions.
      Atomic force microscopy and transmission electron microscopy revealed that the
      structural integrity of the methanoarchaeal cells is destroyed within 4 h after
      incubation with AMPs. The disruption of the cell envelope of M. smithii, M.
      stadtmanae, and M. mazei within a few minutes of exposure was verified by using
      LIVE/DEAD staining. Our results strongly suggest that the release of AMPs by
      eukaryotic epithelial cells is a potent defense mechanism targeting not only
      bacteria, but also methanoarchaea.

PMID- 22585227
TI  - Levofloxacin inhibits rhinovirus infection in primary cultures of human tracheal
      epithelial cells.
AB  - Respiratory virus infections, including infections with rhinoviruses (RVs), are
      related to exacerbations of chronic obstructive pulmonary disease (COPD). A new
      quinolone antibiotic, levofloxacin (LVFX), has been used to treat bacterial
      infections that cause COPD exacerbations as well as bacterial infections that are
      secondary to viral infection in COPD patients. However, the inhibitory effects of
      LVFX on RV infection and RV infection-induced airway inflammation have not been
      studied. We examined the effects of LVFX on type 14 rhinovirus (RV14) (a major
      human RV) infection of human tracheal epithelial cells pretreated with LVFX. LVFX
      pretreatment reduced the RV14 titer, the level of cytokines in the supernatant,
      the amount of RV14 RNA in the cells after RV14 infection, and the cells'
      susceptibility to RV14 infection. LVFX pretreatment decreased the mRNA level of
      intercellular adhesion molecule 1 (ICAM-1), a receptor for RV14, in the cells and
      the concentration of the soluble form of ICAM-1 in the supernatant before RV14
      infection. LVFX pretreatment also decreased the number and the fluorescence
      intensity of the acidic endosomes from which RV14 RNA enters the cytoplasm. LVFX
      pretreatment inhibited the activation of nuclear factor kappaB proteins,
      including p50 and p65, in nuclear extracts. LVFX pretreatment did not reduce the
      titers of RV2 (a minor human RV) but reduced the titers of RV15 (a major human
      RV). These results suggest that LVFX inhibits major-group rhinovirus infections
      in part by reducing ICAM-1 expression levels and the number of acidic endosomes.
      LVFX may also modulate airway inflammation in rhinoviral infections.

PMID- 22585228
TI  - Efficacy of rifaximin vaginal tablets in treatment of bacterial vaginosis: a
      molecular characterization of the vaginal microbiota.
AB  - Bacterial vaginosis (BV) is a common vaginal disorder characterized by an
      alteration of the vaginal bacterial morphotypes, associated with sexually
      transmitted infections and adverse pregnancy outcomes. The purpose of the present
      study was to evaluate the impact of different doses of rifaximin vaginal tablets
      (100 mg/day for 5 days, 25 mg/day for 5 days, and 100 mg/day for 2 days) on the
      vaginal microbiota of 102 European patients with BV enrolled in a multicenter,
      double-blind, randomized, placebo-controlled study. An integrated molecular
      approach based on quantitative PCR (qPCR) and PCR-denaturing gradient gel
      electrophoresis (PCR-DGGE) was used to investigate the effects of vaginal tablets
      containing the antibiotic. An increase in members of the genus Lactobacillus and
      a decrease in the BV-related bacterial groups after the antibiotic treatment were
      demonstrated by qPCR. PCR-DGGE profiles confirmed the capability of rifaximin to
      modulate the composition of the vaginal microbial communities and to reduce their
      complexity. This molecular analysis supported the clinical observation that
      rifaximin at 25 mg/day for 5 days represents an effective treatment to be used in
      future pivotal studies for the treatment of BV.

PMID- 22585229
TI  - Amixicile, a novel inhibitor of pyruvate: ferredoxin oxidoreductase, shows
      efficacy against Clostridium difficile in a mouse infection model.
AB  - Clostridium difficile infection (CDI) is a serious diarrheal disease that often
      develops following prior antibiotic usage. One of the major problems with current
      therapies (oral vancomycin and metronidazole) is the high rate of recurrence.
      Nitazoxanide (NTZ), an inhibitor of pyruvate:ferredoxin oxidoreductase (PFOR) in
      anaerobic bacteria, parasites, Helicobacter pylori, and Campylobacter jejuni,
      also shows clinical efficacy against CDI. From a library of ~250 analogues of
      NTZ, we identified leads with increased potency for PFOR. MIC screens indicated
      in vitro activity in the 0.05- to 2-MUg/ml range against C. difficile. To improve
      solubility, we replaced the 2-acetoxy group with propylamine, producing
      amixicile, a soluble (10 mg/ml), nontoxic (cell-based assay) lead that produced
      no adverse effects in mice by oral or intraperitoneal (i.p.) routes at 200 mg/kg
      of body weight/day. In initial efficacy testing in mice treated (20 mg/kg/day, 5
      days each) 1 day after receiving a lethal inoculum of C. difficile, amixicile
      showed slightly less protection than did vancomycin by day 5. However, in an
      optimized CDI model, amixicile showed equivalence to vancomycin and fidaxomicin
      at day 5 and there was significantly greater survival produced by amixicile than
      by the other drugs on day 12. All three drugs were comparable by measures of
      weight loss/gain and severity of disease. Recurrence of CDI was common for mice
      treated with vancomycin or fidaxomicin but not for mice receiving amixicile or
      NTZ. These results suggest that gut repopulation with beneficial (non-PFOR)
      bacteria, considered essential for protection against CDI, rebounds much sooner
      with amixicile therapy than with vancomycin or fidaxomicin. If the mouse model is
      indeed predictive of human CDI disease, then amixicile, a novel PFOR inhibitor,
      appears to be a very promising new candidate for treatment of CDI.

PMID- 22585230
TI  - Pseudomonas aeruginosa exopolysaccharide Psl promotes resistance to the biofilm
      inhibitor polysorbate 80.
AB  - Polysorbate 80 (PS80) is a nonionic surfactant and detergent that inhibits
      biofilm formation by Pseudomonas aeruginosa at concentrations as low as 0.001%
      and is well tolerated in human tissues. However, certain clinical and laboratory
      strains (PAO1) of P. aeruginosa are able to form biofilms in the presence of
      PS80. To better understand this resistance, we performed transposon mutagenesis
      with a PS80-resistant clinical isolate, PA738. This revealed that mutation of
      algC rendered PA738 sensitive to PS80 biofilm inhibition. AlgC contributes to the
      biosynthesis of the exopolysaccharides Psl and alginate, as well as
      lipopolysaccharide and rhamnolipid. Analysis of mutations downstream of AlgC in
      these biosynthetic pathways established that disruption of the psl operon was
      sufficient to render the PA738 and PAO1 strains sensitive to PS80-mediated
      biofilm inhibition. Increased levels of Psl production in the presence of
      arabinose in a strain with an arabinose-inducible psl promoter were correlated
      with increased biofilm formation in PS80. In P. aeruginosa strains MJK8 and
      ZK2870, known to produce both Pel and Psl, disruption of genes in the psl but not
      the pel operon conferred susceptibility to PS80-mediated biofilm inhibition. The
      laboratory strain PA14 does not produce Psl and does not form biofilms in PS80.
      However, when PA14 was transformed with a cosmid containing the psl operon, it
      formed biofilms in the presence of PS80. Taken together, these data suggest that
      production of the exopolysaccharide Psl by P. aeruginosa promotes resistance to
      the biofilm inhibitor PS80.

PMID- 22585231
TI  - Low expression of ULK1 is associated with operable breast cancer progression and
      is an adverse prognostic marker of survival for patients.
AB  - ULK1 plays an important role in autophagy which is widely involved in the
      development of breast cancer. However, the function and expression of ULK1 in
      human breast cancer is still scarcely explored. In this study, we showed that the
      mRNA and protein levels of ULK1 decreased in 10 of 14 (71.4 %) breast cancer
      tissues, compared with matched normal tissues. Furthermore, immunohistochemical
      staining of ULK1 was performed on the tissue microarray containing 298 non
      metastatic invasive breast primary cancer tissues and 73 matched adjacent
      noncancerous tissues. 70.1 % breast cancer specimens displayed none to weak
      staining of ULK1, however, 78.1 % adjacent noncancerous specimens showed moderate
      to strong staining of ULK1. Statistical analysis revealed that ULK1 expression
      was negatively correlated with tumor size (r = -0.176, P = 0.002), lymph node
      status (r = -0.115, P = 0.048), and pathological stage (r = -0.177, P = 0.002).
      The log-rank test showed that patients with lower level of ULK1 had a significant
      shorter distant metastasis-free survival time (P = 0.008) and cancer-related
      survival time (P = 0.008). Multivariate Cox regression analysis found that ULK1
      expression was recognized as an independent prognostic factor (P = 0.034). In
      addition, a significant positive correlation between expression of ULK1 and LC3A
      (r = 0.401, P < 0.001), and a significant negative correlation between expression
      of ULK1 and p62 (r = -0.226, P < 0.001) were observed in our breast cancer
      cohort. These findings suggest that decreased expression of ULK1 is associated
      with breast cancer progression, together with closely related to decreased
      autophagic capacity. ULK1 also may be used as a novel prognostic biomarker for
      breast cancer patients.

PMID- 22585233
TI  - Novel insights into pathogenesis, diagnosis and treatment of antiphospholipid
      syndrome.
AB  - PURPOSE OF REVIEW: To provide an update of recent insights into the pathogenesis,
      diagnosis and treatment of antiphospholipid syndrome (APS) from current
      literature. RECENT FINDINGS: beta2GPI was recently implicated in the pathogenesis
      of thrombosis. High titres of anti-beta2GPI antibodies are present in patients
      with triple positivity which highlight its importance. Consensus guidelines have
      been published to standardise diagnostic assays and once implemented may yield
      more accurate diagnoses of APS. An 'aPL score' has been formulated to improve the
      detection and outcomes of patients. New oral anticoagulants, statins and
      concomitant therapy with warfarin and aspirin have been identified as potential
      novel therapeutic interventions for thrombotic APS. Advances in the pathogenesis
      of obstetric APS have occurred, such as the concept of redefining the syndrome as
      inflammatory and clearer identification of the roles of complement, beta2GPI and
      annexin 5. Independent risk factors for pregnancy failure have been recognised
      and when combined with clinical and laboratory features may improve patient
      outcomes. Interventions involving adjusted doses of low molecular weight heparin
      in combination with aspirin have shown promising results from initial studies.
      SUMMARY: Recent insights into the pathogenesis of APS have unveiled novel areas
      for treatment intervention. Diagnostic criteria and recommendations have been
      revised and formulated to provide consensus and standardisation for diagnosis.

PMID- 22585234
TI  - Implications of peripheral muscular and anatomical development for the
      acquisition of lingual control for speech production: a review.
AB  - OBJECTIVES: Normally developing children learn to produce intelligible speech
      during rapid, non-uniform growth of their articulators and other vocal tract
      structures. The purpose of this review is to focus attention on the consequences
      of peripheral growth and development for the acquisition of lingual control for
      speech production. This paper (1) reviews physiological underpinnings of tongue
      shaping and movements that are likely to be changing in young children; (2)
      estimates, from previously published studies, the net consequences of growth of
      multiple vocal tract structures on lingual control; (3) integrates our findings
      with the example of [R] production, and (4) highlights areas where further
      investigations would be most helpful. PATIENTS AND METHODS: The authors searched
      the literature, including the PubMed database, for studies of the development of
      muscle proteins, muscle fibers, and motor units of the tongue, and of the growth
      of the tongue, jaw, adenoids, soft and hard palates, oral and pharyngeal
      cavities, and the vocal tract as a whole. CONCLUSIONS: Substantial anatomical and
      muscular data sets focused on children from 1-4 years of age, and rigorous
      definitions of the tongue boundaries are needed.

PMID- 22585235
TI  - Barriers in access to insecticide-treated bednets for malaria prevention: an
      analysis of Cambodian DHS data.
AB  - BACKGROUND & OBJECTIVES: The distribution of insecticide-treated bednets (ITNs),
      as an alternative to untreated bednets or no bednet at all, not only directly
      prevents the mosquito from biting an individual, but kills the mosquito as well.
      This reduces the mosquito infestation at the household and community levels.
      However, barriers may exist limiting the effectiveness of malaria prevention by
      these tactics. Objectives of the study were to assess current disparities in
      access to ITNs, what factors may be associated with disparities in access and the
      progress of antimalaria interventions. METHODS: This study examined disparities
      in access to intervention resources between rural and urban locations by
      assessing the percentage of households in each area that has at least one ITN.
      Demographic Health Survey (DHS) 2005 data from 16,823 survey respondents from
      Cambodia were explored, examining the ratio of households with at least one ITN
      according to various socioeconomic determinants. Statistical analysis was done
      using Chi-square and logistic regression with SPSS. RESULTS: Problematic distance
      from ITN distributors, rural location, and poverty were all associated with
      greater unlikelihood of possession of least one household ITN. CONCLUSION: In
      order to effectively combat high malaria prevalence, interventions need to be
      refocused on increasing accessibility to ITNs. The limitations of this study
      require further investigation into alternative socioeconomic determinants.

PMID- 22585232
TI  - Effects of delta-9-tetrahydrocannabinol on evaluation of emotional images.
AB  - There is growing evidence that drugs of abuse alter processing of emotional
      information in ways that could be attractive to users. Our recent report that
      Delta9-tetrahydrocannabinol (THC) diminishes amygdalar activation in response to
      threat-related faces suggests that THC may modify evaluation of emotionally
      salient, particularly negative or threatening, stimuli. In this study, we
      examined the effects of acute THC on evaluation of emotional images. Healthy
      volunteers received two doses of THC (7.5 and 15 mg; p.o.) and placebo across
      separate sessions before performing tasks assessing facial emotion recognition
      and emotional responses to pictures of emotional scenes. THC significantly
      impaired recognition of facial fear and anger, but it only marginally impaired
      recognition of sadness and happiness. The drug did not consistently affect
      ratings of emotional scenes. THC's effects on emotional evaluation were not
      clearly related to its mood-altering effects. These results support our previous
      work, and show that THC reduces perception of facial threat. Nevertheless, THC
      does not appear to positively bias evaluation of emotional stimuli in general.

PMID- 22585236
TI  - Sandfly saliva of Lutzomyia ovallesi (Diptera: Psychodidae) as a possible marker
      for the transmission of Leishmania in Venezuela Andes region.
AB  - BACKGROUND & OBJECTIVES: The saliva of the Phlebotominae is highly immunogenic to
      the vertebrate host and is a determining factor in the Leishmania infection. The
      aim of this work was to study the saliva of Lutzomyia ovallesi as a possible risk
      marker for the transmission of Leishmania. METHODS: Two populations of L.
      ovallesi from different geographical areas and subjected to different
      environmental conditions were compared by geometric morphometry of the wings, by
      protein profile analysis of salivary glands and by assessing the presence of anti
      saliva protein in human sera confronted with laboratory L. ovallesi saliva.
      RESULTS: The results showed differences in the isometric size and structure of
      the wings but no allometric effects. Protein profiles of salivary glands of both
      the L. ovallesi populations studied were found to be similar, based on 11 protein
      bands with molecular weights ranging from 16 to 99 kDa. Anti-saliva antibodies
      were present in human sera, but human sera infected and uninfected with
      leishmaniasis could not be differentiated. INTERPRETATION & CONCLUSION: We
      conclude that the saliva of laboratory-reared L. ovallesi is representative of
      that of the wild population. It is suggested to study the presence of anti-saliva
      antibodies in other species of sandflies and mosquitoes.

PMID- 22585237
TI  - Molecular diagnosis of Old World leishmaniasis: real-time PCR based on
      tryparedoxin peroxidase gene for the detection and identification of Leishmania
      spp.
AB  - BACKGROUND & OBJECTIVES: Rapid and accurate diagnosis and identification of
      Leishmania sp causing cutaneous leishmaniasis is crucial in control and
      therapeutic programs. The problem of diagnosis with traditional methods is that
      they have a low sensitivity or time consuming but molecular techniques would be
      an alternative method for rapid and accurate diagnosis. In this work,
      tryparedoxine peroxidase gene-based real-time PCR was used for accurate
      identification of Leishmania spp causing Old-World cutaneous leishmaniasis.
      METHODS: In this study, biopsies of specimens were taken from the ulcerative
      sites in 100 patients and used for direct microscopy, culture in NNN or fixed in
      alcohol for identification of Leishmania spp using tryparedoxin peroxidase gene
      based realtime PCR (qPCR). RESULTS: Using direct microscopy and culture method,
      Leishmania parasites were isolated from 68 out of 100 patient samples. However,
      13 patients with negative finding on traditional tests, had positive results on
      RT-PCR test. After melting curve analysis of PCR product, Leishmania major in 75
      and L. tropica in 4 cases were identified. The sensitivity and specificity of RT
      PCR for diagnosis of cutaneous leishmaniasis was 98.7 and 59.8%, respectively.
      CONCLUSION: Results of this study showed that RT-PCR was the most sensitive
      diagnostic test for cutaneous leishmaniasis and represents a tool for rapid
      species identification.

PMID- 22585238
TI  - Immune peptides modelling of Culex pipiens sp by in silico methods.
AB  - BACKGROUND: In the past 60 years, antibiotics have been critical in the fight
      against infectious diseases caused by bacteria and other microbes. Development of
      resistance to the antibiotics is emerging as a major public health issue which
      has resulted in the search for new antibiotics in order to maintain a pool of
      effective drugs at all times. Currently, there is a great interest in cationic
      peptides as antibiotics. These are reported to destroy the host cell membrane
      rather interacting with the other cell components, which may not face emergence
      of resistance. In mosquitoes, peptides like cecropin, defensin and gambicin
      reported to have inhibitory effect on bacteria, fungi and parasites. These
      peptides are well-characterized at both the biochemical and molecular level from
      Anopheles and Culex species, yet their 3D structures were not reported. METHODS:
      Defensin, cecropin and gambicin immune peptides of Culex pipiens was
      characterised to have antiparasitic, antibacterial and antifungal activities.
      Since the crystal structure of defensin, cecropin and gambicin are not yet
      available their 3D structures were determined using homology modeling and Rosetta
      fragment insertion methods and were validated. RESULTS: Stereo chemical
      evaluation indicated that defensin and gambicin showed that 100% residues of
      constructed model lie in the most favoured and allowed regions. Cecropin iso
      forms A and B showed 100% while C showed 97.6% residues that lie in most favoured
      and allowed regions, which indicated quality models. CONCLUSION: Predicted model
      provide insight into their structure and aid in the development of novel
      antibiotic peptides.

PMID- 22585239
TI  - Laboratory colonization of Lucilia sericata Meigen (Diptera: Caliphoridae) strain
      from Hashtgerd, Iran.
AB  - BACKGROUND & OBJECTIVES: The treatment of wounds with live green bottle fly
      larvae is receiving considerable attention in many countries. Laboratory rearing
      of Lucilia sericata is crucially important for the treatment of wounds. STUDY
      DESIGN: The study was carried out for mass rearing of green bottle flies from
      April to November 2010. Hand catch and net trap baited with beef and cattle liver
      were used to collect adult flies from the field. The collected samples were
      placed in appropriately labeled tubes and sent to the laboratory. Adult stage
      flies reared in the insectary were used for species identification using specific
      keys. RESULTS: A total of 89 flies (55 females and 34 males) were collected from
      Hashtgerd area. In the first generation, 299 flies were produced in the
      laboratory including 105 (35.12%) males, and 194 (64.88%) females. The
      female/male sex ratio was 1.61 for parents, whereas it was 1.84, 1.30 for F1 and
      F2 generations respectively. In total, 432 flies were reared in F3 generation
      including 173 (40.04%) males, and 259 (59.96%) females, and the sex ratio was
      1.49. CONCLUSION: Setting up the mass rearing of sheep blowfly at the School of
      Public Health, Tehran University of Medical Sciences is an important step in
      producing candidate flies for the treatment of myiasis by maggot therapy in
      future.

PMID- 22585240
TI  - Malaria healthcare policy change in Kenya: implications on sales and marketing of
      antimalarials.
AB  - BACKGROUND & OBJECTIVES: Malaria healthcare policy change in Kenya aimed at
      improving the control of malaria but faced a number of challenges in
      implementation related to marketing of the drugs. This research investigated the
      effect of the change of the national malaria policy on drug sales and strategic
      marketing responses of antimalarial pharmaceutical companies in Kenya. STUDY
      DESIGN: A descriptive cross-sectional design was employed to describe the
      existing state of antimalarials market in Kenya after the change of the malaria
      healthcare policy. RESULTS & CONCLUSION: Policy change did result in an increase
      in the sales of Coartem(r). Novartis Pharma recorded a 97% growth in sales of
      Coartem(r) between 2003 and 2004. However, this increase was not experienced by
      all the companies. Further, SPs (which had been replaced as first-line therapy
      for malaria) registered good sales. In most cases, these sales were higher than
      the sales of Coartem(r). Generally, the sales contribution of SPs and generic
      antimalarial medicines exceeded that of Coartem(r) for most distributors. The
      most common change made to marketing strategies by distributors (62.5%) was to
      increase imports of antimalarials. A total of 40% of the manufacturers preferred
      to increase their budgetary allocation for marketing activities. In view of the
      fact that continued sale of SP drugs and limited availability of AL poses the
      risk of increasing the incidence of malaria in Kenya, it is therefore,
      recommended that pharmacy surveillance systems be strengthened to ensure drugs
      that have been rendered non-viable or that prescription-only medicines are not
      sold contrary to the national guidelines.

PMID- 22585241
TI  - Mosquito species geographical distribution in Iraq 2009.
AB  - BACKGROUND & OBJECTIVES: Mosquitoes transmit diseases to >700 million people
      annually. Malaria kills three million persons every year, including one child
      every 30 sec. Worldwide there are >3000 mosquito species. In Iraq, 37 species
      have been identified in different surveys over several decades. We conducted an
      entomological survey to determine the mosquito species and their distribution in
      Iraq in 2009. METHODS: Between January 20 and December 31, 2009, mosquitoes in
      houses in 12 Iraqi provinces were collected and speciated. Five to 10 villages
      were selected randomly in each province and in each village 10 houses were
      selected randomly to collect mosquitoes and the density of mosquitoes per room
      was calculated. Kits for entomological investigation were used and the collected
      mosquitoes were sent to the vector borne disease section laboratory for
      classification using the Naval Medical Research Unit 3 standard classification
      key. RESULTS: A total of 29,156 mosquitoes were collected, representing two
      genera: Anopheles (n=13,268, or 46% of the total collected) and Culex (n=15,888,
      or 54% of the total collected). Four Anopheles (An. pulcherrimus, An. stephensi,
      An. superpictus, and An. sacharovi) and one Culex (Cx. pipiens) species were
      identified. Anopheles pulcherrimus was found in 11 provinces, An. stephensi in 7,
      An. superpictus in 2 and An. sacharovi in one province, while Cx. pipiens was
      found in all the 12 provinces. Two peaks of mosquito density were found: the
      first from April-June and the other from September-October. INTERPRETATION &
      CONCLUSION: There are clear differences in Anopheles mosquito species
      geographical distribution and density among Iraqi provinces, while Cx. pipiens
      mosquitoes are distributed all over Iraq. All mosquito genera show clear seasonal
      density variation. The study highlights that the manual mosquito classification
      is not enough to identify all the species of mosquitoes in Iraq.

PMID- 22585242
TI  - Status of insecticide resistance in malaria vector, Anopheles culicifacies in
      Chhattisgarh state, India.

PMID- 22585243
TI  - Insecticide resistance status in Anopheles culicifacies in Madhya Pradesh,
      central India.

PMID- 22585244
TI  - Susceptibility of malaria vectors to insecticides in Gadchiroli district
      (Maharashtra), India.

PMID- 22585245
TI  - Entomological surveillance in a recent autochthonous malaria area of Spain.

PMID- 22585246
TI  - Pleuropulmonary scrub typhus: a summary of Thai cases.

PMID- 22585247
TI  - Unusual presentations of vivax malaria: a report of two cases.

PMID- 22585248
TI  - Acute disseminated encephalomyelitis and dengue fever: comment.

PMID- 22585249
TI  - Old, cold and at risk.

PMID- 22585250
TI  - An evidence-based approach to  diagnosis and management of cellulitis.
AB  - Community nurses are involved in caring for people who are at risk of cellulitis.
      The community nurse may be involved in dressing leg ulcers and may refer a
      patient with suspected cellulitis for appropriate treatment. Community nurses are
      also increasingly involved in delivery of outpatient antibiotic therapy (OPAT).
      As the role of the community nurse expands to encompass diagnosis, prescribing,
      delivery of OPAT and in some cases the decision on when to switch from IV to oral
      antibiotics, it is essential that the nurse is aware of the evidence base for
      diagnosis and treatment of lower leg cellulitis. This paper discusses the reasons
      for the increasing incidence of lower leg cellulitis and explores the evidence
      base for treatment.

PMID- 22585251
TI  - Improving sleep management  in people with Parkinson's.
AB  - This article considers the practicality and patient benefits of transferring
      evidence-based sleep management skills to community health professionals. Sleep
      disturbances are among the most frequently reported and poorly managed non-motor
      symptoms in Parkinson's. But, despite their prevalence, sleep problems in
      Parkinson's are often under-recognized, under-diagnosed and inadequately treated.
      To raise awareness and improve patient care in Parkinson's, a three-day sleep
      management course was developed for Parkinson's disease nurse specialists (PDNSs)
      practising within NHS Scotland. The course aimed to transfer skills in health
      education as applied to sleep and insomnia; the assessment of sleep; the practice
      of sleep hygiene; delivering relaxation methods; the use of stimulus control and
      sleep restriction procedures; and cognitive approaches to insomnia management.
      Between June 2010 and July 2011, 38 PDNSs and practising occupational therapists
      undertook the course. Interviews and evaluations with patients and professionals
      were carried out afterwards. Patients reported a reduction in anxiety over sleep
      problems, feeling able to manage their sleep, and having a sense of control over
      their sleep. Programme outcomes suggest that the training model used is feasible
      and practical; the resources designed for clinical use are practical and
      relevant; and that the initiative as a whole represents a valid and affordable
      investment in patient wellbeing.

PMID- 22585252
TI  - Mental health issues in primary care: implementing policies in practice.
AB  - Recent health policies highlight the important role that mental health
      contributes to our general wellbeing, and call for parity of esteem between
      physical and mental health. The bidirectional relationship between physical and
      mental health culminates in high prevalence rates of mental disorders in primary
      care settings. Despite these prevalence findings being known for some time,
      evidence would suggest that at times mental disorders are being overlooked. This
      article, set in context to policy, patient prevalence, practice and professional
      development, outlines a range of factors that can impede mental health delivery
      and proposes ways in which primary care nurses can strengthen their activity and
      involvement at various levels.

PMID- 22585253
TI  - Enabling patients to die at home:  hidden tensions and barriers.

PMID- 22585254
TI  - Made to measure? Assessing feasibility of quality indicators for district
      nursing.
AB  - Scant empirical information exists regarding the quality of district nursing (DN)
      services. This article reports the testing of 31 quality indicators (QI) in
      practice. METHOD: Twelve DN teams provided patient notes for audit. External
      auditors completed audit forms by cross-referencing between DN office records,
      patient notes from home, electronic GP records and discussions with DN team
      leaders. A patient experience questionnaire was piloted. FINDINGS: 277 (77%)
      patients' records were audited. Access to records was problematic. QIs required
      further refinement of their wording, modification of inclusion criteria, deletion
      of some QIs and inclusion of others. Telephone administration of the patient
      experience questionnaire was not feasible for the DN patient population.
      CONCLUSIONS: QIs can not be used 'off the shelf' and need testing and
      modification before routine use. Trained, external auditors with clinical
      backgrounds ensure an informed, uniform, objective approach to data collection,
      which is desirable as QIs might inform commissioners in a competitive field in
      future.

PMID- 22585255
TI  - Need to know: consent and the nurse's duty to warn of risk.
AB  - This article, the second in a series on consent to examination and treatment,
      considers a district nurse's duty to warn patients of the risks inherent in
      treatment. The article discusses whether patients are entitled to full and honest
      answers to their questions about risks, and whether district nurses can lie to
      anxious patients about the risks of treatment.

PMID- 22585256
TI  - Activating support for patient self-management to boost quality of life.

PMID- 22585257
TI  - Care in a cold climate.

PMID- 22585259
TI  - Two-step hydrothermal synthesis of submicron Li(1+x)Ni(0.5)Mn(1.5)O(4-delta) for
      lithium-ion battery cathodes (x = 0.02, delta = 0.12).
AB  - A facile two-step hydrothermal method is developed for the large-scale
      preparation of lithium nickel manganese oxide spinel as a cathode material for
      lithium ion batteries. In the reaction, nickel is introduced in a first step at
      neutral pH, followed by lithium insertion under base to form a product having
      composition Li(1.02)Ni(0.5)Mn(1.5)O(3.88). The X-ray diffraction pattern and
      Raman spectroscopy of the synthesized material support a cubic Fd3m structure in
      which Ni and Mn are disordered on the 16d Wyckoff site, necessary for good
      cycling characteristics. XP spectroscopy and elemental analysis confirms that Mn
      remains reduced in the final product (Z(Mn) = 3.82) and that two different
      chemical environments for Ni exist on the surface. SEM imaging shows a primary
      particle size of ~200 nm, and galvanostatic cycling of the material vs. Li(+/0)
      gives a reversible gravimetric capacity of ~120 mA h g(-1) at 1 C rate (147 mA g(
      1)) with reversible cycling up to 1470 mA g(-1), supported by rapid Li(+)
      diffusion. The capacity fade at 1 C is substantial, 17.3% over the first 100
      cycles between 3.4 and 5.0 V. However, when the voltage limits are altered, the
      capacity retention is excellent: nearly 100% when cycled either between 3.4 and
      4.4 V (where oxygen vacancies are not electrochemically active) or 89% when
      cycled between 4.4 and 5.0 V (where the Jahn-Teller active Mn(4+/3+) couple is
      not accessed).

PMID- 22585260
TI  - Dynamic pore network model of surface heterogeneity in brine-filled porous media
      for carbon sequestration.
AB  - Trapping of carbon in deep underground brine-filled reservoirs is a promising
      approach for the reduction of atmospheric greenhouse gas emissions. However,
      estimation of the amount of carbon dioxide (CO(2)) that can be captured in a
      given reservoir and the long-term storage stability remain a challenge. One
      difficulty lies in the estimation of local capillary pressure effects that arise
      from mineral surface heterogeneity inherent in underground geological formations.
      As a preliminary step to address this issue, we have performed dynamic pore
      network modelling (PNM) simulations of two-phase immiscible flow in two
      dimensional structured porous media with contact angle heterogeneity under
      typical reservoir conditions. We begin by characterizing the network with a
      single, uniform contact angle. We then present saturation patterns for networks
      with homogeneous and heterogeneous contact angles distributions, based on two
      common reservoir minerals: quartz and mica, both of which have been well
      characterized experimentally for their brine-CO(2) contact angles. At lower flow
      rates, we found moderately higher saturations for the heterogeneous networks than
      for the homogeneous ones. To characterize the fingering patterns, we have
      introduced R as the ratio of filled throats to the total network saturation.
      Based on this measure, the heterogeneous networks demonstrated thicker fingering
      patterns than the homogeneous networks. The computed saturation patterns
      demonstrate the importance of considering surface heterogeneity in pore-scale
      modelling of deep saline aquifers.

PMID- 22585261
TI  - Mental health:  a public health priority.

PMID- 22585262
TI  - International Nurses' Day:  a cause for celebration.

PMID- 22585263
TI  - Moisture-associated skin damage: aetiology, prevention and treatment.
AB  - The concept of excessive moisture causing damage to the skin is not a new one,
      and provides a rationale for many fundamental nursing interventions. Although
      traditionally thought of as a specific problem of continence care, it is a common
      problem encountered in many different patient groups. As a consequence the
      umbrella term moisture-associated skin damage (MASD) has been introduced to
      describe the spectrum of damage that occurs in response to the prolonged exposure
      of a patient's skin to perspiration, urine, faeces or wound exudate. It is
      generally accepted that MASD consists of four main separate conditions, each
      having slightly different aetiologies, all of which will be explored in this
      paper. Careful assessment can help distinguish between the four and enable
      appropriate prevention and treatment interventions to be implemented. Whatever
      causes the excessive moisture, effective interventions should consist of the
      adoption of a structured skin care regime to cleanse and protect, methods to keep
      the skin dry, controlling the source of the excessive moisture and treating any
      secondary infection.

PMID- 22585264
TI  - Does interprofessional education provide a global template?

PMID- 22585265
TI  - Student perceptions of sudden cardiac arrest: a qualitative inquiry.
AB  - Sudden cardiac arrest (SCA) is the number one cause of death in young athletes in
      high school and university settings. Survival and outcomes of SCA is dependent on
      appropriate recognition of symptoms and immediate cardiopulmonary resuscitation
      (CPR), along with a shock from an automatic external defibrillator (AED).  The
      three aims of the authors' study presented in this article were: to describe
      university students' perceptions and beliefs about sudden cardiac arrest, to
      describe university students' understanding of an AED and their level of
      preparedness to recognize and respond to a life threatening emergency event, and
      to identify university students' experiences of responding to handling life
      threatening emergency events. Qualitative methodology was employed using semi
      structured interviews and thematic analysis. Three major themes emerged from data
      analysis: confusion, uncertainty, and fear/uncomfortableness. These themes
      characterised participant's perceptions about SCA. The authors concluded that a
      lack of understanding of what SCA is and participants' inability to respond to an
      emergency event was evident.

PMID- 22585266
TI  - Student nurses' personality traits and the nursing profession: part 2.
AB  - Individuals' attitudes stem partly from their personality traits, which may
      influence their interpersonal relationships with patients. Although personality
      traits are somewhat genetically determined, research has found that there are
      other factors that may influence this, such as self-esteem, family, social and
      clinical environments, and education. Part one of this article explained the
      research process of this cross-sectional descriptive study, which assessed the
      personality traits of two cohorts of nursing/midwifery students (n=116, aged 19
      44 years) in their third year of the Diploma/BSc (Hons) programme at the
      University of Malta (Baldacchino and Galea, 2012). Data were collected in 2006
      using the NEO Five-Factor Inventory (Costa and McCrae, 1992c). In part two, the
      authors demonstrate that students obtained low neuroticism scores, average
      openness scores, and high agreeableness, extraversion and conscientiousness
      scores. Irrespective of nursing/midwifery programmes, age and gender, similar
      mean scores were identified in all five personality domains. These findings are
      consistent with previous studies, with some exceptions related to significant
      differences in gender and religiosity. Further larger scale longitudinal research
      is recommended on nursing/midwifery and allied healthcare students, to exhibit a
      possible profile pattern across time and other influencing factors.

PMID- 22585267
TI  - Current assessment of patient safety education.
AB  - The purpose of this literature review was to examine current evidence on how
      student nurses and nursing faculty members perceived the integration of patient
      safety education in preregistration/undergraduate nursing training. Databases
      searched from January 2000 to April 2011 included CINAHL, PsycINFO, British
      Nursing Index, PubMed, AMED, Academic Science, Midline, Cochrane Library
      Database, Web of Knowledge, Ovid Nursing Database, Wiley Online Library and
      Science Direct. In total, 77 articles were initially found, although only 15 were
      included in the author's review. Of these, 5 papers were research-based articles
      that examined aspects of patient safety education in undergraduate/pre
      registration nursing training, and 9 papers were literature review and discussion
      based, which provided insight into the experience, assessment, evaluation or
      implementation of patient safety education curriculum in nursing education. The
      author's literature review highlights the continuing lack of research on patient
      safety education in undergraduate/preregistration nursing training and, in
      particular, outlines areas in nursing education which need to be addressed to
      develop patient-safety-friendly nursing curricula.

PMID- 22585268
TI  - What are pre-registration nurses taught about caring for children?
AB  - Nurse education curricula have to be continually reviewed to ensure that content
      remains applicable to contemporary healthcare developments. In this article, the
      authors report the findings of a research study that investigated the children's
      nursing component taught in all non-children's BSc Nursing degree programmes in
      Irish colleges. The aim of the study was to identify how European Union
      directives and national curriculum guidelines are interpreted in colleges, and to
      clarify the preparation that non-children's pre-registration nursing students
      receive with respect to caring for children. The authors explored aspects related
      to children's nursing in all non-children's undergraduate pre-registration
      programmes, including curriculum content and its delivery, assessments and
      practice experiences. Data were collected by a specifically designed
      questionnaire based on the Requirements and Standards for Nurse Education
      Programmes (An Bord Altranais, 2005a; b). A university ethics committee provided
      ethical approval. The response rate was 54% (n=7), and data were analysed using
      SPSS 16 and content analysis. The authors' findings illustrated that the
      requirements and standards of all nursing programmes are interpreted in a variety
      of ways regarding children's nursing. Nationally, nursing content related to
      children needs to be reviewed in all nursing programmes to ensure consistency
      among providers. Healthcare requirements for children and families need to be
      heightened within curricula for all disciplines.

PMID- 22585269
TI  - Interprofessional working: the only way forward.

PMID- 22585270
TI  - Looking ahead: tomorrow's nursing profession and care delivery.

PMID- 22585271
TI  - Exploring patients' rights: what does the NHS Constitution tell us?
AB  - On 8 March 2012, the NHS published the latest version of its Constitution. In
      this article, the author explores the background of the debate regarding
      patients' rights and entitlements in the NHS. The author also discusses the
      provisions of the NHS Constitution, noting that it is largely a statement of
      existing principles, rather than a bold statement of rights. The paper suggests
      that, in some instances, its discussion of rights may suggest that patients have
      broader rights than may in fact be the case. The Constitution is currently under
      review, and the author recommends that the way forward for a society where the
      provision of care is likely to be more complex would be the introduction of a
      Patients' Rights Act.

PMID- 22585273
TI  - Professional development: from staff nurse to nurse consultant. Part 11:
      financing your development.

PMID- 22585272
TI  - Deprivation of liberty safeguards:  a human rights issue.

PMID- 22585274
TI  - Inspection: an essential tool  for service improvement.

PMID- 22585280
TI  - Linear attenuation coefficient and buildup factor of MCP-96 alloy for dose
      accuracy, beam collimation, and radiation protection.
AB  - The linear attenuation coefficients and buildup factor of MCP-96 alloy were
      determined for (60)Co, (54)Mn, and (137)Cs gamma emitters and a NaI detector. The
      thickness of the MCP-96 attenuator was varied from 1 to 4 cm. A collimated beam
      of gamma rays was allowed to pass through various thicknesses of the MCP-96
      alloy. The attenuated beam was detected by a NaI detector, and data were recorded
      by a multichannel analyzer. The run was repeated without the collimator for broad
      beam geometry. For each run, the attenuated beam intensity was normalized by the
      intensity of the unattenuated incident beam obtained by removing the attenuators.
      Linear attenuation coefficients were determined by plotting of the intensity of
      the collimated beam against the attenuator thickness. For every thickness of the
      alloy, the ratio of the attenuated to the unattenuated beam was found to be
      higher in broad-beam geometry as compared to the same ratio in narrow-beam
      geometry. We used the difference in these ratios in broad and narrow-beam
      geometries to calculate the buildup factor. The buildup factor was found to
      increase with beam energy and attenuator thickness. Variation in the source-to
      detector distance gave a lower value of the buildup factor for a small and a
      large distance and a higher value for an intermediate distance. The buildup
      factor was found to be greater than 1 in all cases. We conclude that the buildup
      factor must be calculated and incorporated for dose correction and precision when
      the MCP-96 alloy is used for tissue compensation or radiation shielding and
      protection purposes.

PMID- 22585281
TI  - The best of the European Heart Journal: look back with pride.

PMID- 22585275
TI  - Role of dietary therapies in the prevention and treatment of hypertension.
AB  - Blood pressure naturally rises with increasing age. The rate of change in blood
      pressure with age is regulated in part by genetic factors, but can also be
      altered through sustained dietary modification. Dietary approaches to modify
      blood pressure remain an important part of cardiovascular health promotion, which
      is especially important given the aging of the general population coupled with
      the increasing prevalence of obesity and metabolic disturbances. Specific
      modification of dietary components such as macronutrients and micronutrients
      could be helpful to lower blood pressure and alter the slope of blood pressure
      change whereas nutritional supplements are less likely to have a substantial
      beneficial effect. Population-wide generalizations regarding diet are impractical
      as individualized strategies are more likely to be successful in facilitating
      long-term benefits in improving blood-pressure control. Consequently, more effort
      needs to be focused on evaluating data from large-scale observational and
      interventional studies and interpreting their information in a clinically
      relevant manner, which is likely to be helpful for individual patients. Providing
      education on the relationship between diet and blood pressure from an early age
      is most likely to produce tangible benefits.

PMID- 22585282
TI  - The Clinical Atlas of Intravascular Optical Coherence Tomography for iPad.
AB  - The first comprehensive educational tool devoted exclusively to intravascular OCT
      is now available from PCR publishing.

PMID- 22585283
TI  - Examining gender differences for gambling engagement and gambling problems among
      emerging adults.
AB  - Gambling is fast becoming a public health problem in the United States,
      especially among emerging adults (18-25 year olds). Since 1995, rates have
      recently doubled with around 7-11 % of the emerging adult population having
      problems with gambling (Shaffer et al. in Am J Public Health 89(9):1369-1376,
      1999; Cyders and Smith in Pers Individ Diff 45(6):503-508, 2008). Some states
      have lowered their gambling age to 18 years old; in turn, the gambling industry
      has recently oriented their market to target this younger population. However,
      little is known about the gender variation and the factors placing emerging
      adults at risk for getting engaged and developing problems with gambling. The
      purpose of the study was to determine the risk factors accounting for gender
      differences at the two levels of gambling involvement: engagement and problems.
      Mediation analyses revealed that impulsive coping and risk-taking were
      significant partial mediators for gender differences on engagement in gambling.
      Men took more risks and had lower levels of impulsive coping than women, and
      those who took more risks and had lower levels of impulsive coping were more
      likely to engage in gambling. Risk-taking and social anxiety were the significant
      mediators for gender differences in problems with gambling. Men took more risks
      and were more socially anxious than women, and greater risk-taking and more
      socially anxious individuals tended to have more problems with gambling.
      Implications for counseling preventions and intervention strategies are
      discussed.

PMID- 22585284
TI  - Effect of the CYP2C19 genotype on the pharmacokinetics of icotinib in healthy
      male volunteers.
AB  - PURPOSE: Icotinib hydrochloride {4-[(3-ethynylphenyl)amino]-6,7-benzo-12-crown-4
      quinazoline hydrochloride}, a novel epidermal growth factor receptor (EGFR)
      tyrosine kinase inhibitor (TKI), was designed for the treatment of non-small cell
      lung cancer (NSCLC). In the present study, we investigated the influence of the
      CYP2C19*2 and CYP2C19*3 alleles on the pharmacokinetics of icotinib in healthy
      Chinese volunteers. METHODS: In a single-dose pharmacokinetic study, 12 healthy
      Chinese volunteers received an oral dose of 600 mg of icotinib. Plasma was
      sampled for up to 72 h post-dose, followed by quantification of icotinib by
      liquid chromatography-mass spectrometry/mass spectrometry (LC-MS-MS). RESULTS:
      Five subjects genotyped as homozygous extensive metabolizers (CYP2C19*1/*1), 6
      subjects genotyped as heterozygous extensive metabolizers (CYP2C19*1/*2 or
      CYP2C19*1/*3), and 1 subject genotyped as a poor metabolizer (CYP2C19*2/*3) and
      was withdrawn from the research because of urticaria. The mean icotinib AUC(0
      infinity) and C(max) (14.56 +/-5.31 h mg/L and 2.32 +/- 0.49 MUg/mL) in
      homozygous EMs was 1.56 and 1.41-fold lower than that in heterozygous EMs (22.7
      +/- 6.11 and 3.28 +/- 0.48, P = 0.046 and 0.047). The mean CL/F (44.18 +/- 12.17
      L/h) in homozygous EMs was 1.55-fold higher than that in heterozygous EMs (28.42
      +/- 9.23 L/h, P = 0.013). CONCLUSIONS: The data showed that the pharmacokinetics
      of icotinib differ significantly between homozygous EMs and heterozygous EMs in
      CYP2C19.

PMID- 22585285
TI  - Pharmacokinetics and pharmacodynamics of single-dose oral tolvaptan in fasted and
      non-fasted states in healthy Caucasian and Japanese male subjects.
AB  - PURPOSE: To compare the pharmacokinetics and pharmacodynamics of tolvaptan in
      Caucasian and Japanese healthy male subjects under fasting and non-fasting
      conditions. METHODS: This was a single-center, parallel-group, randomized, open
      label, three-period crossover trial of single oral doses of tolvaptan 30 mg under
      fasting and non-fasting [a high-fat, high-calorie meal (HFM) or Japanese standard
      meal] conditions in 25 healthy male Caucasian subjects and 24 healthy male
      Japanese subjects. Pharmacodynamic endpoints were urine volume and fluid balance
      for 0 to 24 h postdose. RESULTS: In the fasted state, the plasma tolvaptan C(max)
      and AUC(infinity) geometric mean ratios (90 % confidence interval) were 1.105
      (0.845-1.444) and 1.145 (0.843-1.554) for Japanese compared to Caucasian
      subjects. A HFM increased the C(max) and AUC(infinity) values by about 1.15-fold
      in both Japanese and Caucasian subjects.. Twenty-four-hour urine volumes
      paralleled pharmacokinetic changes, but the increases were not clinically
      significant. Fluid balance in the Japanese men was 1.4- to 2.0-fold more negative
      than that in the Caucasian men. CONCLUSION: Tolvaptan pharmacokinetics is not
      clinically significantly affected by race. Body weight is a factor that affects
      exposure. Tolvaptan can be administered with or without food.

PMID- 22585286
TI  - Agrobacterium tumefaciens-mediated transformation for investigating pathogenicity
      genes of the phytopathogenic fungus Colletotrichum sansevieriae.
AB  - Agrobacterium tumefaciens-mediated transformation (AtMT) has become a common
      technique for DNA transformation of yeast and filamentous fungi. In this study,
      we first established a protocol of AtMT for the phytopathogenic fungus
      Colletotrichum sansevieriae. Binary T-DNA vector containing the hygromycin B
      phosphotransferase gene controlled by the Aspergillus nidulans gpdA promoter and
      the trpC terminator was constructed with pCAMBIA0380 and used with three
      different strains LBA4404, GV3101, and GV2260 of A. tumefaciens. Transformants
      were most effectively obtained when GV2260 and C. sansevieriae Sa-1-2 were co
      cultivated; there were about 320 transformants per 10(6) spores. When 1,048
      transformants were inoculated on Sansevieria trifasciata, three transformants
      were found to have completely lost their pathogenicity and two transformants
      displayed reduced pathogenicity. All of the five transformants had a single copy
      of T-DNA in their genomes. The three pathogenicity-deficient transformants were
      subjected to thermal asymmetric interlaced polymerase chain reaction and the
      reaction allowed us to amplify the sequences flanking the left and/or right
      borders. The flanking sequences of the two transformants, M154 and M875, showed
      no homology to any sequences in databases, but the sequences of M678 contained
      motifs of alpha-1,3-glucan synthase, suggesting that the gene might contribute to
      the pathogenicity of C. sansevieriae. This study describes a useful method for
      investigating pathogenicity genes in C. sansevieriae.

PMID- 22585287
TI  - Cerebrovascular risk factors and brain microstructural abnormalities on diffusion
      tensor images in HIV-infected individuals.
AB  - HIV-associated neurocognitive disorder remains prevalent in HIV-infected
      individuals despite effective antiretroviral therapy. As these individuals age,
      comorbid cerebrovascular disease will likely impact cognitive function. Effective
      tools to study this impact are needed. This study used diffusion tensor imaging
      (DTI) to characterize brain microstructural changes in HIV-infected individuals
      with and without cerebrovascular risk factors. Diffusion-weighted MRIs were
      obtained in 22 HIV-infected subjects aged 50 years or older (mean age = 58 years,
      standard deviation = 6 years; 19 males, three females). Tensors were calculated
      to obtain fractional anisotropy (FA) and mean diffusivity (MD) maps. Statistical
      comparisons accounting for multiple comparisons were made between groups with and
      without cerebrovascular risk factors. Abnormal glucose metabolism (i.e., impaired
      fasting glucose, impaired glucose tolerance, or diabetes mellitus) was associated
      with significantly higher MD (false discovery rate (FDR) critical p value =
      0.008) and lower FA (FDR critical p value = 0.002) in the caudate and lower FA in
      the hippocampus (FDR critical p value = 0.004). Pearson correlations were
      performed between DTI measures in the caudate and hippocampus and age- and
      education-adjusted composite scores of global cognitive function, memory, and
      psychomotor speed. There were no detectable correlations between the neuroimaging
      measures and measures of cognition. In summary, we demonstrate that brain
      microstructural abnormalities are associated with abnormal glucose metabolism in
      the caudate and hippocampus of HIV-infected individuals. Deep gray matter
      structures and the hippocampus may be vulnerable in subjects with comorbid
      abnormal glucose metabolism, but our results should be confirmed in further
      studies.

PMID- 22585288
TI  - Disease-modifying drugs for multiple sclerosis and JC virus expression.
AB  - Natalizumab-associated progressive multifocal leukoencephalopathy in multiple
      sclerosis (MS) occurred in two individuals also treated with interferon beta1a,
      raising concerns about the interaction of these disease-modifying agents and
      leading to the recommendation to avoid their concomitant administration. However,
      type I interferons are antiviral. Using a real-time quantitative polymerase chain
      reaction for the detection and quantification of the John Cunningham virus (JCV),
      DNA in peripheral blood mononuclear cells (PBMCs), and urine in MS patients, we
      tested the hypothesis that MS disease-modifying drugs (DMD) qualitatively and
      quantitatively alter JCV prevalence and viral copy numbers. Two hundred thirty
      nine patients were enrolled in a cross-sectional study in which blood and urine
      specimens were collected at a single time and 37 newly diagnosed, treatment-naive
      MS patients were enrolled in a longitudinal study in which specimens were
      obtained at diagnosis and 6 months after treatment initiation. JCV DNA was
      detected in PBMCs of only two patients (0.07 %), but was commonly detected in the
      urine (46.8 %) in this population. There was no effect of DMDs on blood or
      urinary JCV prevalence or viral copy numbers with either glatiramer acetate
      (Copaxone(r)) or interferon-beta therapy (Avonex(r), Betaseron(r), or Rebif(r)).
      The small number of patients on other therapies precluded meaningful comment
      about their effects. No obvious effect of the platform DMDs on JCV prevalence was
      observed even for the interferon-betas.

PMID- 22585289
TI  - Sleepless nights: the effect of socioeconomic status, physical activity, and
      lifestyle factors on sleep quality in a large cohort of Australian women.
AB  - The aims of this study were to examine: (1) the association between
      sociodemographic and lifestyle factors and sleep quality in a population-based
      cohort of Australian women and (2) possible influence of reproductive status and
      mental and physical health factors on these associations. Data on 3,655 women
      (mean age = 46.6 years, range 34.3-67.4) were obtained from the Mater Hospital
      University of Queensland Study of Pregnancy for this cross-sectional study. Self
      rated sleep quality was assessed using the Pittsburgh Sleep Quality Index. For
      the purpose of this study, two cutoff points (scores 5 and 10) were used to
      divide women into three categories: normal (65.2%), moderately poor (26.4%), and
      very poor sleep quality (8.5%). Other covariates were measured at 21-year follow
      up as well. After adjusting for reproductive status, mental and physical health,
      there were significant associations between moderately poor sleep quality and
      education and between very poor sleep quality and unemployment, both measures of
      socioeconomic status. In addition, work-related exertion was associated with
      increased rates of moderately poor sleep quality, whereas those women undertaking
      moderate exercise were less likely to experience very poor sleep quality.
      Independent associations between sociodemographic factors and exercise with
      moderately poor and very poor sleep quality were identified. These findings
      demonstrate the dynamic nature of the association between exercise/exertion,
      socioeconomic status, and sleep quality and highlight the importance of taking
      these into consideration when dealing with issues of poor sleep quality in women.

PMID- 22585290
TI  - Dealing with a serious  adverse event.

PMID- 22585292
TI  - Cardiovascular failure, inotropes and vasopressors.

PMID- 22585291
TI  - Atrial fibrillation.

PMID- 22585293
TI  - The collapsing pulse.

PMID- 22585295
TI  - Enantioselective Friedel-Crafts alkylation of indoles with 2-enoylpyridine-N
      oxides catalyzed by glucoBOX-Cu(II) complex.
AB  - The glucosamine derived glucoBOX-Cu(II) complex was found to be a unique
      catalytic system for enantioselective Friedel-Crafts alkylation of indoles with 2
      enoylpyridine-1-oxides. A large number of 3-alkylated indole derivatives were
      prepared using 5 mol% glucoBOX-Cu(II) complex in excellent yields with high
      enantioselectivity up to 99% ee.

PMID- 22585294
TI  - The impact of bladder neck mucosal eversion during open radical prostatectomy on
      bladder neck stricture and urinary extravasation.
AB  - PURPOSE: To determine whether the bladder neck mucosal eversion (BNM-eversion)
      during radical retropubic prostatectomy (RRP) reduces the risk of bladder neck
      stricture (BNS) and of peri-anastomotic extravasation (PAE) in postoperative
      cystography. METHODS: Two hundred and eleven patients with clinically localized
      prostate cancer underwent RRP and were prospectively randomized into patients
      with BNM-eversion (group I) and without BNM-eversion (group II). All patients
      underwent an evaluation of PAE by retrograde cystography on postoperative day 8.
      We assessed BNS after 6 months. RESULTS: Ninety-two patients with and 113
      patients without BNM-eversion were included. There was no significant difference
      in baseline characteristics, including age, TNM-classification, Gleason score,
      PSA, prostate volume, and blood loss in both groups. A complete follow-up of 6
      months for BNS was available for 188 patients (89.1 %). Sixteen BNS out of 188
      patients were recorded, 4.7 % (n = 4) in group I and 11.7 % (n = 12) in group II
      (p = 0.09). Data from 205 out of 211 patients were available for the evaluation
      of the extravasation by cystography. Peri-anastomotic extravasation was
      detectable in 11.96 %, (11/205) in group I and in 21.24 % (24/205) in group II (p
      = 0.08). CONCLUSION: BNM-eversion does not have a positive influence on the
      prevention of bladder neck strictures. Peri-anastomotic extravasation detected by
      cystography does not correlate with a formation of bladder neck stricture.

PMID- 22585296
TI  - Siglec-7 tetramers characterize B-cell subpopulations and leukemic blasts.
AB  - Cell surface glycosylation has important regulatory functions in the maturation,
      activation, and homeostasis of lymphocytes. The family of human sialic acid
      binding immunoglobulin-like lectins (siglecs) comprises inhibitory as well as
      activating receptors intimately involved in the regulation of immune responses.
      Analyses of the interaction between siglecs and glycans are hampered by the low
      affinity of this interaction. Therefore, we expressed siglec-7 in eukaryotic
      cells, allowing for glycosylation, and oligomerized the protein in analogy to MHC
      tetramers. Using this tool, flow cytometric analysis of lymphocytes became
      possible. Sialic acid-dependent binding of siglec-7 tetramers was confirmed by
      glycan array analysis and loss of siglec tetramer binding after neuraminidase
      treatment of lymphocytes. In contrast to most lymphocyte subpopulations, which
      showed high siglec-7 ligand expression, B-cell subpopulations could be further
      subdivided according to different siglec-7 ligand expression levels. We also
      analyzed blasts from acute lymphoblastic leukemias of the B-cell lineage as well
      as the T-cell lineage, since malignant transformation is often associated with
      aberrant cell surface glycosylation. While pediatric T-ALL blasts highly
      expressed siglec-7 ligands, siglec-7 ligands were barely detectable on cALL
      blasts. Taken together, oligomerization of recombinant soluble siglec-7 enabled
      flow cytometric identification of physiologic lymphocyte subpopulations and
      malignant blasts.

PMID- 22585297
TI  - Reliability of non-lethal surveillance methods for detecting ranavirus infection.
AB  - Ranaviruses have been identified as the etiologic agent in many amphibian die
      offs across the globe. Polymerase chain reaction (PCR) is commonly used to detect
      ranavirus infection in amphibian hosts, but the test results may vary between
      tissue samples obtained by lethal and non-lethal procedures. Testing liver
      samples for infection is a common lethal sampling technique to estimate ranavirus
      prevalence because the pathogen often targets this organ and the liver is easy to
      identify and collect. However, tail clips or swabs may be more practicable for
      ranavirus surveillance programs compared with collecting and euthanizing animals,
      especially for uncommon species. Using PCR results from liver samples for
      comparison, we defined false-positive test results as occurrences when a non
      lethal technique indicated positive but the liver sample was negative. Similarly,
      we defined false-negative test results as occurrences when a non-lethal technique
      was negative but the liver sample was positive. Using these decision rules, we
      estimated false-negative and false-positive rates for tail clips and swabs. Our
      study was conducted in a controlled facility using American bullfrog Lithobates
      catesbeianus tadpoles; false-positive and false-negative rates were estimated
      after different periods of time following exposure to ranavirus. False-negative
      and false-positive rates were 20 and 6%, respectively, for tail samples, and 22
      and 12%, respectively, for swabs. False-negative rates were constant over time,
      but false-positive rates decreased with post-exposure duration. Our results
      suggest that non-lethal sampling techniques can be useful for ranavirus
      surveillance, although the prevalence of infection may be underestimated when
      compared to results obtained with liver samples.

PMID- 22585298
TI  - Quantification of piscine reovirus (PRV) at different stages of Atlantic salmon
      Salmo salar production.
AB  - The newly described piscine reovirus (PRV) appears to be associated with the
      development of heart and skeletal muscle inflammation (HSMI) in farmed Atlantic
      salmon Salmo salar L. PRV seems to be ubiquitous among fish in Norwegian salmon
      farms, but high viral loads and tissue distribution support a causal relationship
      between virus and disease. In order to improve understanding of the distribution
      of PRV in the salmon production line, we quantified PRV by using real-time PCR on
      heart samples collected at different points in the life cycle from pre-smolts to
      fish ready for slaughter. PRV positive pre-smolts were found in about 36% of the
      freshwater cohorts and a general increase in viral load was observed after their
      transfer to seawater. A reduction in viral loads was recorded when fish
      approached slaughter (18 mo in sea cages). Sequencing of positive samples did not
      support the hypothesis that outbreaks are caused by the spreading of a particular
      (virulent) strain of PRV.

PMID- 22585299
TI  - Horizontal transmission of nervous necrosis virus between turbot Scophthalmus
      maximus and Atlantic cod Gadus morhua using cohabitation challenge.
AB  - Experimental horizontal transmission of nervous necrosis virus (NNV) originating
      from halibut Hippoglossus hippoglossus was studied through cohabitation of
      intraperitoneally (i.p.) injected fish with uninfected fish for 125 d. The
      experimental groups consisted of i.p. injected turbot Scophthalmus maximus or
      i.p. injected Atlantic salmon Salmo salar with turbot, salmon or Atlantic cod
      Gadus morhua cohabitants. The initial weights were cod 10 g, salmon 40 g and
      turbot 3 g. NNV was detected in brain, eye and spleen by real-time reverse
      transcriptase PCR (qRT-PCR) in cod cohabitated with i.p. injected turbot after 90
      and 125 d, suggesting NNV infection was transmitted horizontally from the turbot
      to cod. NNV was not detected in salmon that were cohabitated with i.p. challenged
      turbot or salmon. This study shows that NNV strains belonging to the Barfin
      Flounder Nervous Necrosis Virus (BFNNV) clade may be transmitted from halibut to
      cod via water. Hence there is a potential risk of horizontal transmission of the
      virus from farmed halibut to farmed and wild cod. The lack of detection of NNV in
      cohabitant salmon suggests that this fish species is less susceptible than cod,
      or not susceptible, to horizontal NNV transmission. This result might be
      influenced by the size of salmon, viral load in i.p. injected cohabitants or
      insufficient duration of the experiment.

PMID- 22585300
TI  - European freshwater VHSV genotype Ia isolates divide into two distinct
      subpopulations.
AB  - Viral haemorrhagic septicaemia (VHS), caused by the novirhabdovirus VHSV, often
      leads to significant economic losses to European rainbow trout production. The
      virus isolates are divided into 4 distinct genotypes with additional subgroups
      including sublineage Ia, isolates of which are the main source of outbreaks in
      European rainbow trout farming. A significant portion of Danish rainbow trout
      farms have been considered endemically infected with VHSV since the first disease
      outbreak was observed in the 1950s. However, following a series of sanitary
      programs starting in 1965, VHSV has not been detected in Denmark since January
      2009. Full-length G-genes of all Danish VHSV isolates that were submitted for
      diagnostic analyses in the period 2004-2009 were sequenced and analysed. All 58
      Danish isolates from rainbow trout grouped with sublineage Ia isolates.
      Furthermore, VHSV isolates from infected Danish freshwater catchments appear to
      have evolved into a distinct clade within sublineage Ia, herein designated clade
      Ia-1, whereas trout isolates originating from other continental European
      countries cluster in another distinct clade, designated clade Ia-2. In addition,
      phylogenetic analyses indicate that VHSV Ia-1 strains have caused a few outbreaks
      in Germany and the UK. It is likely that viruses have been transmitted from
      infected site(s) out of the Danish environment, although a direct transmission
      pathway has not been identified. Furthermore, VHSV Ia-2 isolates seem to have
      been transmitted to Denmark at least once. Interestingly, one viral isolate
      possibly persisted in a Danish watershed for nearly 4 yr without detection
      whereas other subclades of VHSV isolates appear to have been eliminated, probably
      because of implemented eradication procedures.

PMID- 22585301
TI  - Nyctiphanes couchii as intermediate host for the acanthocephalan Bolbosoma
      balaenae in temperate waters of the NE Atlantic.
AB  - Cystacanths of the acanthocephalan Bolbosoma balaenae (Gmelin, 1790) were found
      encapsulated in the cephalothorax of the euphausiid Nyctiphanes couchii (Bell,
      1853) from temperate waters in the NE Atlantic Ocean. Euphausiids were caught in
      locations outside the Ria de Vigo in Galicia, NW Spain, and prevalence of
      infection was up to 0.1%. The parasite was identified by morphological
      characters. Cystacanths were 8.09 +/- 2.25 mm total length (mean +/- SD) and had
      proboscises that consisted of 22 to 24 longitudinal rows of hooks, each of which
      had 8 or 9 hooks per row including 2 or 3 rootless ones in the proboscis base and
      1 field of small hooks in the prebulbar part. Phylogenetic analyses of 18S rDNA
      and cytocrome c oxidase subunit I revealed a close relationship with other taxa
      of the family Polymorphidae (Meyer, 1931). The results extend northwards ot the
      known distribution of B. balaenae. Taxonomic affiliation of parasites and trophic
      ecology in the sampling area suggest that N. couchii is the intermediate host for
      B. balenae, and we suggest that the whales Balaenoptera physalus (Linnaeus, 1758)
      and B. acutorostrata (Lacepede, 1804) are its definitive hosts. This life cycle
      is probably completed with or without paratenic hosts.

PMID- 22585302
TI  - High serotonin levels due to the presence of the acanthocephalan Hexaglandula
      corynosoma could promote changes in behavior of the fiddler crab Uca spinicarpa.
AB  - Between February and June 2010, 113 fiddler crabs Uca spinicarpa were collected
      from the Chuburna lagoon system on the northern coast of the Yucatan Peninsula,
      Mexico. Of the 68 crabs gathered outside their burrows, 13 were infected with 25
      cystacanths of Hexaglandula corynosoma (intensity of infection from 1 to 5) and
      the remaining 55 crabs were uninfected. The other 45 crabs were found inside
      their burrows and only one was found infected with 1 cystacanth of H. corynosoma.
      Serotonin (5-HT) levels were higher in the group of crabs infected with H.
      corynosoma in contrast to the group of uninfected crabs and the group of those
      infected with other parasites. A redundancy analysis corroborated a positive
      relationship between 5-HT and the intensity of infection with H. corynosoma. In
      contrast, dopamine levels remained similar among different groups of crabs.

PMID- 22585303
TI  - Pseudocollinia brintoni gen. nov., sp. nov. (Apostomatida: Colliniidae), a
      parasitoid ciliate infecting the euphausiid Nyctiphanes simplex.
AB  - A novel parasitoid ciliate, Pseudocollinia brintoni gen. nov., sp. nov. was
      discovered infecting the subtropical sac-spawning euphausiid Nyctiphanes simplex
      off both coasts of the Baja California peninsula, Mexico. We used microscopic,
      and genetic information to describe this species throughout most of its life
      cycle. Pseudocollinia is distinguished from other Colliniidae genera because it
      exclusively infects euphausiids, has a polymorphic life cycle, and has a small
      cone-shaped oral cavity whose left wall has a field of ciliated kinetosomes and
      whose opening is surrounded on the left and right by 2 'oral' kineties (or
      ciliary rows) that terminate at its anterior border. Two related species that
      infect different euphausiid species from higher latitudes in the northeastern
      Pacific Ocean, Collinia beringensis Capriulo and Small, 1986, briefly redescribed
      herein, and Collinia oregonensis Gomez-Gutierrez, Peterson, and Morado, 2006, are
      transferred to the genus Pseudocollinia. P. brintoni has between 12 and 18
      somatic kineties, and its oral cavity has only 2 oral kineties, while P.
      beringensis comb. nov. has more somatic kineties, including 3 oral kineties. P.
      oregonensis comb. nov. has an intermediate number of somatic kineties. P.
      beringensis comb. nov. also infects Thysanoessa raschi (a new host species). SSU
      rRNA and cox1 gene sequences demonstrated that Pseudocollinia ciliates are
      apostome ciliates and that P. brintoni is different from P. beringensis comb.
      nov. High densities of rod-shaped bacteria (1.7 um length, 0.2 to 0.5 um
      diameter) were associated with P. brintoni. After euphausiid rupture, high
      concentrations of P. brintoni and bacteria cluster to form 3 to 6 cm long
      filaments where tomites encyst and transform to the phoront stage; this is a
      novel place for encystation. P. brintoni may complete its life cycle when the
      euphausiids feed on these filaments.

PMID- 22585304
TI  - Granulosa cell tumour in a harbour porpoise (Phocoena phocoena) from German
      waters.
AB  - Neoplastic diseases in harbour porpoises Phocoena phocoena have rarely been
      described, and there are no reported gonadal stromal tumours. A 12 yr old female
      harbour porpoise was stranded on the North Sea coast of Schleswig-Holstein,
      Germany. Necropsy findings included a severe granulomatous pneumonia, pregnancy
      and a left ovarian tumour. Respiratory insufficiency was the likely cause of
      death. There was a multinodular mass composed of cords with peripherally
      palisading cells within the left ovary. The histological and cytological
      appearance of the neoplasm was suggestive of a granulosa cell tumour; supportive
      immunohistochemical stains, including those for vimentin, cytokeration,
      carcinoembryonic antigen, c-kit, chromogranin and alpha-smooth muscle action,
      were negative.

PMID- 22585307
TI  - [Rules and regulations applying to incidents in radiotherapy].
AB  - AIMS AND PURPOSE: Radiotherapy is an essential and reliable element of the
      treatment armamentarium in oncology. Numerous rules, regulations, and protocols
      minimize the associated risks. It can, however, never be excluded that errors in
      the treatment delivery chain result in inadequate tumor doses or unnecessary
      damage to organs at risk. A legal framework governs the management of such
      incidents. The most important European and North American regulations are
      reported. RESULTS: Various directives issued by the European Union are
      differently implemented nationally. This applies particularly to the
      characterization of incidents that must be reported to authorities. Reporting
      thresholds, audit systems, and the extent of the integration of voluntary
      reporting systems vary. CONCLUSION: Radiotherapy incidents are dealt with
      differently on an international level. Changes are to be expected based on the
      European Basic Safety Standards Directive that is currently being prepared and
      will have to be implemented nationally in due course.

PMID- 22585305
TI  - DC-derived TSLP promotes Th2 polarization in LPS-primed allergic airway
      inflammation.
AB  - Thymic stromal lymphopoietin (TSLP) plays important roles in the pathogenesis of
      allergic diseases. Whether and how TSLP is involved in the initial priming of T
      helper type-2 (Th2) differentiation against harmless antigen remains unclear.
      Using an intranasal sensitization protocol with OVA and LPS, we showed that TSLP
      signaling is required for low-dose LPS-induced Th2 inflammation, but not for high
      dose LPS-induced Th1 immunity. We further demonstrated that low-dose LPS
      activated bone marrow-derived dendritic cells expressed relatively high Tslp but
      low Il12a, and were able to prime naive DO11.10 T cells to differentiate into Th2
      cells in a TSLP-dependent manner. After transfer into wild-type recipient mice,
      the low-dose LPS-activated OVA-loaded dendritic cells (DCs) induced airway
      eosinophilia, but primed neutrophil-dominated airway inflammation when TSLP
      deficient DCs were used. These studies demonstrate that TSLP released by DCs in
      response to a low concentration of LPS plays a role in priming Th2
      differentiation and thus may serve as a polarizing third signal, in addition to
      antigen/MHC class II and co-stimulatory factors, from antigen-presenting DCs to
      direct effector T-cell differentiation.

PMID- 22585306
TI  - Aqueous speciation and electrochemical properties of a water-soluble manganese
      phthalocyanine complex.
AB  - The speciation behavior of a water-soluble manganese(III) tetrasulfonated
      phthalocyanine complex was investigated with UV-visible and electron paramagnetic
      resonance (EPR) spectroscopies, as well as cyclic voltammetry. Parallel-mode EPR
      (in dimethylformamide : pyridine solvent mix) reveals a six-line hyperfine
      signal, centered at a g-value of 8.8, for the manganese(III) monomer,
      characteristic of the d(4)S = 2 system. The color of an aqueous solution
      containing the complex is dependent upon the pH of the solution; the
      phthalocyanine complex can exist as a water-bound monomer, a hydroxide-bound
      monomer, or an oxo-bridged dimer. Addition of coordinating bases such as borate
      or pyridine changes the speciation behavior by coordinating the manganese center.
      From the UV-visible spectra, complete speciation diagrams are plotted by global
      analysis of the pH-dependent UV-visible spectra, and a complete set of pK(a)
      values is obtained by fitting the data to a standard pK(a) model. Electrochemical
      studies reveal a pH-independent quasi-reversible oxidation event for the
      monomeric species, which likely involves oxidation of the organic ligand to the
      radical cation species. Adsorption of the phthalocyanine complex on the carbon
      working electrode was sometimes observed. The pK(a) values and electrochemistry
      data are discussed in the context of the development of mononuclear water
      oxidation catalysts.

PMID- 22585308
TI  - Optimization of ionic conductivity in solid electrolytes through dopant-dependent
      defect cluster analysis.
AB  - Atomistic simulation based on an energy minimization technique has been carried
      out to investigate defect clusters of R(2)O(3) (R = La, Pr, Nd, Sm, Gd, Dy, Y,
      Yb) solid solutions in fluorite CeO(2). Defect clusters composed of up to six
      oxygen vacancies and twelve accompanied dopant cations have been simulated and
      compared. The binding energy of defect clusters increases as a function of the
      cluster size. A highly symmetric dumbbell structure can be formed by six oxygen
      vacancies, which is considered as a basic building block for larger defect
      clusters. This is also believed to be a universal vacancy structure in an oxygen
      deficient fluorite lattice. Nevertheless, the accurate positions of associated
      dopants depend on the dopant radius. As a consequence, the correlation between
      dopant size and oxygen-ion conductivity has been elucidated based on the ordered
      defect cluster model. This study sheds light on the choice of dopants from a
      physical perspective, and suggests the possibility of searching for optimal solid
      electrolyte materials through atomistic simulations.

PMID- 22585309
TI  - Beyond hyperglycemia in diabetes: role of statin treatment on thrombogenesis
      triggered by inflammation: Editorial to: "Impact of statins on the coagulation
      status of type 2 diabetes patients evaluated by a novel thrombin-generations
      assay" by P. Ferroni et al.

PMID- 22585310
TI  - Lipid fraction quality of milk produced by Minhota (Portuguese autochthonous
      breed) compared to Holstein Friesian cow's.
AB  - BACKGROUND: Minhota and Holstein Friesian cows (15 from each breed) were selected
      from several farms located in the north of Portugal, all under similar feeding
      regime. Milk samples from individual cows were collected once a month, during one
      year, to take into account different lactation stages and feeding seasonal
      changes. RESULTS: Holstein milk was found to have higher content of total
      polyunsaturated fatty acids, omega-6, and trans fatty acids, while Minhota milk
      had significantly higher monounsaturated fatty acids content. No statistical
      differences were observed for omega-3 and saturated fatty acids contents, mostly
      due to the high dispersion observed in Minhota milk samples. The average amount
      of conjugated linoleic acid was higher in Minhota breed, but the high dispersion
      of values reduced the statistical significance. Cholesterol content, expressed as
      mg kg(-1) of fat, was higher in Holstein than in Minhota milk. CONCLUSION: The
      results indicate that Minhota milk has important nutritional qualities that
      deserve attention, but the wide individual variation found within animals from
      this breed suggests a high genetic variability. Following this, the selection of
      some of these animals for intensive milk production could improve milk quality.

PMID- 22585311
TI  - Disparities in preventive health services among Somali immigrants and refugees.
AB  - African immigrants and refugees-almost half of them from Somalia-account for one
      of the fastest-growing groups in the United States. There is reason to suspect
      that Somali-Americans may be at risk for low completion of recommended preventive
      health services. This study's aim was to quantify disparities in preventive
      health services among Somali patients compared with non-Somali patients in an
      academic primary care practice in Rochester, Minn. It also examined the effect of
      medical interpreters, emergency department visits, and primary care visits on the
      completion of preventive services. Rates of pap smears, vaccinations (influenza,
      pneumococcus, and tetanus), lipid screening, colorectal cancer screening, and
      mammography were assessed in Somali and non-Somali patients during the second
      quarter of 2008. Data were collected regarding the utilization of medical
      interpreters, emergency services, and primary care services among Somali
      patients. Results were reported using standard descriptive statistics. Of the
      91,557 patients identified in the database, 810 were Somali. Somali patients had
      significantly lower completion rates of colorectal cancer screening, mammography,
      pap smears, and influenza vaccination than non-Somali patients. Use of medical
      interpreters and primary care services were generally associated with higher
      completion rates of preventive services. There are significant discrepancies in
      the provision of preventive health services to Somali patients compared with that
      of non-Somali patients. These findings suggest the need to identify the root
      causes of these discrepancies so that interventions may be crafted to close the
      gap.

PMID- 22585312
TI  - Impacts of the 2010 Haitian earthquake in the diaspora: findings from Little
      Haiti, Miami, FL.
AB  - In January 2010, a massive earthquake struck Haiti resulting in unprecedented
      damage. Little attention, however, has focused on the earthquake's mental health
      impact in the Haitian diaspora community. As part of an established community
      based participatory research initiative in Little Haiti, the predominately
      Haitian neighborhood in Miami, FL, USA, community health workers conducted
      surveys with neighborhood residents about earthquake-related losses, coping
      strategies, and depressive/traumatic symptomology. Findings reveal the earthquake
      strongly impacted the diaspora community and highlights prominent coping
      strategies. Following the earthquake, only a small percentage of participants
      self-reported engaging in any negative health behaviors. Instead, a majority
      relied on their social networks for support. This study contributes to the
      discourse on designing culturally-responsive mental health initiatives for the
      Haitian diaspora and the ability of existing community-academic partnerships to
      rapidly adapt to community needs.

PMID- 22585313
TI  - Rapid and effective method for the separation of Bacillus subtilis vegetative
      cells and spores.

PMID- 22585314
TI  - Assessing cancer pain.
AB  - Regular assessment for the presence of pain and response to pain management
      strategies should be high priority in cancer patients. Pain is a multidimensional
      experience in cancer patients. Pain management will be most effective when
      treatments are individualized after exploring the various physical and non
      physical components of pain, and the patient and family are educated and involved
      in decision making. This article discusses the various issues that are pertinent
      to the assessment of pain in cancer patients.

PMID- 22585316
TI  - Inorganic polyphosphates in extremophiles and their possible functions.
AB  - Many extremophilic microorganisms are polyextremophiles, being confronted with
      more than one stress condition. For instance, some thermoacidophilic
      microorganisms are in addition capable to resist very high metal concentrations.
      Most likely, they have developed special adaptations to thrive in their living
      environments. Inorganic polyphosphate (polyP) is a molecule considered to be
      primitive in its origin and ubiquitous in nature. It has many roles besides being
      a reservoir for inorganic phosphate and energy. Of special interest are those
      functions related to survival under stressing conditions in all kinds of cells.
      PolyP may therefore have a fundamental part in extremophilic microorganism's
      endurance. Evidence for a role of polyP in the continued existence under acidic
      conditions, high concentrations of toxic heavy metals and elevated salt
      concentrations are reviewed in the present work. Actual evidence suggests that
      polyP may provide mechanistic alternatives in tuning microbial fitness for the
      adaptation under stressful environmental situations and may be of crucial
      relevance amongst extremophiles. The enzymes involved in polyP metabolism show
      structure conservation amongst bacteria and archaea. However, the lack of a
      canonical polyP synthase in Crenarchaea, which greatly accumulate polyP, strongly
      suggests that in this phylum a different enzyme may be in charge of its
      synthesis.

PMID- 22585317
TI  - DNA sequencing of maternal plasma to identify Down syndrome and other trisomies
      in multiple gestations.
AB  - OBJECTIVE: Studies on prenatal testing for Down syndrome (trisomy 21), trisomy
      18, and trisomy 13 by massively parallel shotgun sequencing (MPSS) of circulating
      cell free DNA have been, for the most part, limited to singleton pregnancies. If
      MPSS testing is offered clinically, it is important to know if these trisomies
      will also be identified in multiple pregnancies. METHOD: Among a cohort of 4664
      high-risk pregnancies, maternal plasma samples were tested from 25 twin
      pregnancies (17 euploid, five discordant and two concordant for Down syndrome;
      one discordant for trisomy 13) and two euploid triplet pregnancies [Correction
      made here after initial online publication.]. Results were corrected for GC
      content bias. For each target chromosome (21, 18, and 13), z-scores of 3 or
      higher were considered consistent with trisomy. RESULTS: Seven twin pregnancies
      with Down syndrome, one with trisomy 13, and all 17 twin euploid pregnancies were
      correctly classified [detection rate 100%, 95% confidence interval (CI) 59%-100%,
      false positive rate 0%, 95% CI 0%-19.5%], as were the two triplet euploid
      pregnancies. CONCLUSION: Although study size is limited, the underlying biology
      combined with the present data provide evidence that MPSS testing can be reliably
      used as a secondary screening test for Down syndrome in women with high-risk twin
      gestations.

PMID- 22585315
TI  - Modulation of limbic-cerebellar functional connectivity enables alcoholics to
      recognize who is who.
AB  - Chronic alcoholism is known to disrupt functions served by distributed brain
      systems, including limbic and frontocerebellar circuits involved in resting-state
      and task-activated networks subserving component processes of memory often
      affected in alcoholics. Using an fMRI paradigm, we investigated whether memory
      performance by alcoholics on a face-name association test previously observed to
      be problematic for alcoholics could be explained by desynchronous activity
      between nodes of these specific networks. While in the scanner, 18 alcoholics and
      15 controls performed a face-name associative learning task with different levels
      of processing at encoding. This task was designed to activate the hippocampus,
      cerebellum, and frontal cortex. Alcoholics and controls were also scanned at
      rest. Twelve alcoholics and 12 controls were selected to be matched on face-name
      recognition performance. Task-related fMRI analysis indicated that alcoholics had
      preserved limbic activation but lower cerebellar activation (Crus II) than the
      controls in the face-name learning task. Crus II was, therefore, chosen as a seed
      for functional connectivity MRI analysis. At rest, the left hippocampus and left
      Crus II had positively synchronized activity in controls, while hippocampal and
      cerebellar activities were negatively synchronized in alcoholics. Task engagement
      resulted in hippocampal-cerebellar desynchronization in both groups. We speculate
      that atypical cerebello-hippocampal activity synchronization during rest in
      alcoholics was reset to the normal pattern of asynchrony by task engagement.
      Aberrations from the normal pattern of resting-state default mode synchrony could
      be interpreted as enabling preserved face-name associative memory in alcoholism.

PMID- 22585318
TI  - [Abstracts of the 96th Annual Meeting of the German Society of Pathology. May 31
      June 3, 2012. Berlin, Germany].

PMID- 22585319
TI  - Dignity on the wards: improving hospital care for older people.

PMID- 22585320
TI  - Quality improvement in health care matters.

PMID- 22585322
TI  - What is a quality improvement project?
AB  - This article outlines the why, what and how of quality improvement with the aim
      of encouraging readers to move 'beyond audit' to undertake high calibre quality
      improvement projects within their daily work. It also provides a framework for
      presenting, publishing and disseminating quality improvement findings.

PMID- 22585323
TI  - Quality improvement.
AB  - Quality improvement in health care is a structured analysis of a health-care
      system with a view to improving its performance. This review describes the
      history of quality improvement and its growing application in health care. It
      gives further information for doctors wanting to participate.

PMID- 22585324
TI  - Knowing the risk? NCEPOD 2011: a wake-up call for perioperative practice.
AB  - The high-risk surgical population comprises a minority of cases but accounts for
      the majority of postoperative complications and deaths. The most recent National
      Confidential Enquiry into Patient Outcome and Death review of these patients
      found highly variable standards of care and made several recommendations for
      change.

PMID- 22585325
TI  - Identifying patients at risk of severe Clostridium difficile-associated disease.
AB  - Clostridium difficile infection is responsible for a wide spectrum of clinical
      presentations, ranging from mild diarrhoea to fatal toxic colitis. This article
      reviews factors which may identify individuals who are at high risk of severe C.
      difficile-associated disease, and aims to help clinicians predict patients at
      risk of severe disease.

PMID- 22585326
TI  - Current management of  Barrett's oesophagus.
AB  - Barrett's oesophagus is one of the most common pre-malignant conditions in the
      world and its incidence is increasing. The management of this disease is
      currently the subject of research and debate, with medical, endoscopic and
      operative intervention all having a therapeutic role.

PMID- 22585327
TI  - Kangaroo mother care.
AB  - Kangaroo mother care is a safe, simple method to care for low birth weight
      infants.  This article looks at its origins, what is involved in kangaroo mother
      care and reviews the evidence for improved outcomes resulting from its
      implementation.

PMID- 22585328
TI  - Thomas Wakley:  father of modern medical journalism.

PMID- 22585329
TI  - Who should set the standards  for surgical assessments?
AB  - In light of national policy and educational theory, this article addresses the
      question of who should set the standards for surgical assessments, highlighting
      the multidisciplinary nature of those currently (and potentially) involved.

PMID- 22585330
TI  - Digital gangrene in an elderly patient.

PMID- 22585331
TI  - A rare case of eosinophilia-induced  endomyocardial fibrosis.

PMID- 22585332
TI  - Recurrent symptomatic atrial flutter treated successfully in an 81-year-old
      woman.

PMID- 22585333
TI  - Rapid development of digital nerve neuroma incontinuity.

PMID- 22585334
TI  - Lack of hard evidence gives soft targets.

PMID- 22585336
TI  - The role of vasopressin in  the management of sepsis.

PMID- 22585337
TI  - A systematic analysis of the Braitenberg vehicle 2b for point-like stimulus
      sources.
AB  - Braitenberg vehicles have been used experimentally for decades in robotics with
      limited empirical understanding. This paper presents the first mathematical model
      of the vehicle 2b, displaying so-called aggression behaviour, and analyses the
      possible trajectories for point-like smooth stimulus sources. This sensory-motor
      steering control mechanism is used to implement biologically grounded target
      approach, target-seeking or obstacle-avoidance behaviour. However, the analysis
      of the resulting model reveals that complex and unexpected trajectories can
      result even for point-like stimuli. We also prove how the implementation of the
      controller and the vehicle morphology interact to affect the behaviour of the
      vehicle. This work provides a better understanding of Braitenberg vehicle 2b,
      explains experimental results and paves the way for a formally grounded
      application on robotics as well as for a new way of understanding target seeking
      in biology.

PMID- 22585338
TI  - Heterogeneity in membrane protein genes of porcine epidemic diarrhea viruses
      isolated in China.
AB  - Since late 2010, porcine epidemic diarrhea virus (PEDV) has been re-emerging in
      immunized swine herds with devastating impact in the Hebei province of China.
      Seven prevailing strains of PEDV were isolated from fecal samples out of piglets
      suffering from severe diarrhea. The M gene of the seven PEDV isolates encompasses
      an open reading frame of 681 nucleotides, encoding a protein of 226 amino acids.
      The seven PEDV isolates showed 99.4-99.9 % nucleotide sequence identity and 98.2
      99.1 % deduced amino acid identity. When compared with other Chinese isolates and
      foreign isolates, the seven isolates showed high nucleotide identity with the
      Thailand isolate M-NIAH1005 (99.6-99.9 %) and Korea isolate PFF188 (99.7-100 %),
      but low identity with other Chinese isolates (96.6-99.1 %) and with the vaccine
      strain CV777 used in China (97.8-98.2 %). Phylogenetic analyses showed that all
      seven Chinese field isolates were grouped together in the same cluster. Although
      CV777 was also separated into the same cluster with the seven isolates, they were
      belonged to different sub-cluster. These results showed that the seven prevailing
      isolates in China are closely related phylogenetically to each other and have
      close relationships with the Korean strain PFF188 and Thailand strain M_NIAH1005.
      However, they differ genetically from other Chinese isolates and the vaccine
      strain CV777. Therefore, a more efficient vaccine strain should be chosen to
      prevent outbreaks of PEDV in China.

PMID- 22585339
TI  - Disruption of Bombyx mori nucleopolyhedrovirus ORF71 (Bm71) results in
      inefficient budded virus production and decreased virulence in host larvae.
AB  - The Bombyx mori nucleopolyhedrovirus (BmNPV) is a baculovirus that selectively
      infects domestic silkworm. BmNPV ORF71 (Bm71) is not a core set gene in
      baculovirus and shares 92 % amino acid sequence identity with Autographa
      californica multinucleocapsid NPV ORF88 (Ac88/cg30). Previously, it has been
      reported that virus lacking Ac88 had no striking phenotypes in cell lines or host
      larvae. However, the exact role of Bm71 during BmNPV life cycle remains unknown.
      In the present study, we constructed a Bm71-disrupted (Bm71-D) virus and assessed
      the effect of the Bm71 disruption on viral replication and viral phenotype
      throughout the viral life cycle. Results showed that the Bm71-D bacmid could
      successfully transfect Bm5 cell lines and produce infectious budded virus (BV).
      But the BV titer was 10- to 100-fold lower than that of the wild-type (WT) virus
      during infection, and the decreased BV titer was rescued by Bm71 gene repair
      virus (Bm71-R). A larval bioassay showed that Bm71-D virus took 7.5 h longer than
      the WT to kill Bombyx mori larvae. Transmission electron microscopy analysis
      indicated that the Bm71-D virus-infected cells had typical virogenic stroma,
      bundles of nucleocapsids and polyhedra. Taken together, these results suggest
      that Bm71 has important implications for determining BV yield and virulence in
      viral life cycle even though it is not an essential gene for replication of
      BmNPV.

PMID- 22585340
TI  - Sensitivity of event-related brain potentials to task rules.
AB  - Previous studies have suggested that brain potentials evoked around 300 ms after
      stimulus onset index the processes underlying perceptual decision-making.
      However, the sensitivity of these evoked potentials to the task rules, which link
      sensory perception to the proper action, has not been studied previously. In this
      study, event-related potentials (ERPs) of the human brain were examined when
      subjects randomly performed delayed-matching-to-identity (DMI) and delayed
      matching-to-category (DMC) tasks. The results showed that the amplitudes of the
      brain potentials evoked 228-328 ms after test-stimulus onset varied according to
      the task rules and indexed the processes responsible for decision-making. In
      contrast to these potentials, the preceding evoked activity (< 228 ms) did not
      show any sensitivity to the changes in the subjects' responses and indexed the
      processes responsible for stimulus perception. These findings support the idea
      that the potentials evoked after 228 ms from stimulus onset are influenced by the
      task rules and do not index simple sensory perception.

PMID- 22585343
TI  - Healing and harming.
AB  - As part of a volunteering program, a medical student learns the story of a sick
      infant whose survival was wholly dependent on modern medicine. The family was
      pacified by believing, during pregnancy, that the fetus would be healthy. Poor
      counseling and unethical physician behavior led to the trauma of the family's
      struggle to keep its baby alive, happy, and as healthy as possible. The need for
      adequate, thorough, and individualized counseling is a critical and still
      unfulfilled need in patient care.

PMID- 22585341
TI  - N-acetylserotonin: neuroprotection, neurogenesis, and the sleepy brain.
AB  - N-Acetylserotonin (NAS) is a naturally occurring chemical intermediate in
      biosynthesis of melatonin. Previous studies have shown that NAS has different
      brain distribution patterns from those of serotonin and melatonin, suggesting
      that NAS might have functions other than as a precursor or metabolite of
      melatonin. Indeed, several studies have now shown that NAS may play an important
      role in mood regulation and may have antidepressant activity. Additional studies
      have shown that NAS stimulates proliferation of neuroprogenitor cells and
      prevents some of the negative effects of sleep deprivation. It is believed that
      the antidepressant and neurotrophic actions of NAS are due at least in part to
      the capability on this molecule to activate the TrkB receptor in a brain-derived
      neurotrophic factor-independent manner. Emerging evidence also indicates that NAS
      and its derivatives have neuroprotective properties and protect retinal
      photoreceptor cells from light-induced degeneration. In this review, the authors
      discuss the literature about this exciting and underappreciated molecule.

PMID- 22585342
TI  - A responsive particulate MRI contrast agent for copper(I): a cautionary tale.
AB  - A responsive MION-based MRI contrast agent for the detection of copper(I) is
      presented. Induced agglomeration of azide and acetylene-functionalized magnetite
      nanoparticles via Cu(I)-catalysed Huisgen cycloaddition leads to significant
      decrease in longitudinal relaxivity due to the slow exchange of water molecules
      trapped within the cluster with bulk solvent. Agglomeration leads to an initial
      two-fold increase followed by a sharp and almost complete loss in transverse
      relaxivity for clusters larger than 200 nm in size. The decrease in r(2) for
      clusters reaching the static dephasing regime has two significant implications
      for particulate responsive MRI contrast agents. First, the maximum increase in
      r(2) is barely two-fold, second, since r(2) does not increase continuously with
      increasing cluster size, the r(1)/r(2) ratio cannot be used to determine the
      concentration of an analyte ratiometrically.

PMID- 22585344
TI  - Junctional ectopic tachycardia after infant heart surgery: incidence and
      outcomes.
AB  - Junctional ectopic tachycardia (JET) is an arrhythmia observed almost exclusively
      after open heart surgery in children. Current literature on JET has not focused
      on patients at the highest risk of both developing and being negatively impacted
      by JET. The purpose of this study was to determine the overall incidence of JET
      in an infant patient cohort undergoing open cardiac surgery, to identify patient-
      and procedure-related factors associated with developing JET, and to assess the
      clinical impact of JET on patient outcomes. We performed a nested case-control
      study from the complete cohort of patients at our institution younger than 1 year
      of age who underwent open heart surgery between 2005 and 2010. JET patients were
      compared with an age matched control group undergoing open heart surgery without
      JET regarding potential risk factors and outcomes. The overall incidence of JET
      in infants after open cardiac surgery was 14.3 %. From multivariate analyses,
      complete repair of tetralogy of Fallot [adjusted odds ratio (AOR) 2.0, 95 % CI
      1.12-3.57] and longer aortic cross clamp times (AOR 1.02, 95 % CI 1.01-1.03)
      increased the risk of developing JET. Patients with JET had longer length of
      intubation, intensive care unit stays, and total length of hospitalization, and
      were more likely to require extracorporeal membrane oxygenation support (13 vs.
      4.3 %). JET is a common postoperative arrhythmia in infants after open heart
      operations. Both anatomic substrate and surgical procedure contribute to the
      overall risk of developing JET. Developing JET is associated with worse clinical
      outcomes.

PMID- 22585345
TI  - Retraction note to: Recent advances for the treatment of cocaine abuse: central
      nervous system immunopharmacotherapy.

PMID- 22585347
TI  - What are the patterns of injury and displacement seen in lateral compression
      pelvic fractures?
AB  - BACKGROUND: Lateral compression (LC)-type pelvic fractures encompass a wide
      spectrum of injuries. Current classification systems are poorly suited to help
      guide treatment and do not adequately describe the wide range of injuries seen in
      clinical practice. QUESTIONS/PURPOSES: We therefore (1) defined the spectrum of
      injuries that compose LC fractures with respect to both anterior and posterior
      ring injuries, with particular focus on the morphology of sacral fractures, and
      (2) identified fracture patterns associated with displacement at presentation.
      METHODS: We retrospectively reviewed 318 LC pelvic fractures. Displacement of the
      anterior pelvic ring was identified and measured on plain radiographs and
      posterior displacement was identified by CT. RESULTS: All 318 patients had an
      anterior injury and all but 13 (4%) had a posterior injury; 263 of the 318
      fractures (87%) included a sacral fracture, with 162 of 318 (51%) having an
      anterior incomplete sacral fracture, 53 (17%) a complete simple fracture, and 48
      (15%) a complete comminuted fracture. Forty-two of 318 (13%) had a crescent
      fracture. One hundred six of 318 (33%) were displaced at presentation. There was
      a higher incidence of initial displacement observed in fractures including
      bilateral rami fractures, a comminuted sacral fracture, or a crescent fracture.
      CONCLUSIONS: LC pelvic fractures represent a heterogeneous group of injuries with
      a wide range of associated fracture patterns. In particular, there is a wide
      range of fracture types represented by injuries classified as LC1 (involving any
      sacral fracture). Fractures with more complex sacral fractures, crescent
      fractures, or bilateral pubic rami fractures tend to have higher degrees of
      initial displacement. LEVEL OF EVIDENCE: Level IV, diagnostic study. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 22585346
TI  - [German adrenocortical carcinoma registry. Surgical therapy results and follow-up
      treatment].
AB  - Adrenocortical carcinoma (ACC) is a highly aggressive endocrine disease with an
      incidence of 1-2 cases per million population per year. Due to the low incidence
      of ACC knowledge concerning the surgical management is mainly based on
      retrospective studies or recommendations of isolated experts. Cancer databases,
      such as the German ACC registry are prerequisite to collect and evaluate clinical
      data from a large number of patients. For non-metastatic tumor stages, complete
      tumor resection is the only treatment with curative intent. Open surgery remains
      the recommended approach for ACC. However, in small tumors with uncertain
      malignancy a laparoscopic resection by an expert surgeon can be considered. A
      loco-regional lymphadenectomy should be part of the primary surgical treatment of
      ACC. Tumor recurrence is common even after an apparently complete primary
      resection. Therefore, based on the individual risk (tumor size, resection status,
      proliferation index) adjuvant mitotane treatment is recommended in most patients.
      Patients with low-risk should be included in the ADIUVO trial. In case of tumor
      relapse indications for a reoperation should be strongly considered, especially
      when the time interval since the primary surgery is long (> 12 months) and a
      complete resection of the recurrent disease seems to be feasible.

PMID- 22585348
TI  - A promising thumb Basal joint hemiarthroplasty for treatment of
      trapeziometacarpal osteoarthritis.
AB  - BACKGROUND: Trapeziometacarpal joint osteoarthritis is a painful, disabling
      condition that primarily affects women who are postmenopausal. Arthroplasty has
      been performed to treat this condition; however, subluxation has been a problem
      with all previous implants. We report the results of hemiarthroplasty using a
      prosthesis designed to address the problems associated with previous implants.
      QUESTIONS/PURPOSES: We wished to (1) determine if this prosthesis results in pain
      relief and functional improvement and preserves the appearance of the thumb, (2)
      assess the prosthetic reconstruction during followup, (3) assess complications
      that occur with the use of this prosthesis, and (4) determine the survivorship of
      this prosthesis. METHODS: We performed 159 basal joint hemiarthroplasties (138
      patients) to treat osteoarthritis of the trapeziometacarpal joint. The mean age
      of the patients was 63 years, 78% were women, and all had Eaton-Littler Stage II
      or III changes. Only the damaged articular surfaces of the metacarpal and
      trapezium were excised; no tendon grafts or transfers were performed. Seven
      patients (seven thumbs) were lost to followup and seven (nine thumbs) died,
      leaving 124 patients (143 thumbs) for review. Clinical and radiographic
      assessments were made preoperatively, 12 weeks postoperatively, and annually
      thereafter. Minimum followup was 35 months (mean, 72.1 months; range, 35-120
      months). RESULTS: At latest followup, pain relief occurred in 135 thumbs,
      function improved in 138 thumbs, 139 thumbs were excellent or good in overall
      assessment, and 142 thumbs had good or excellent cosmetic appearance. The mean
      tip pinch improved from 4.9 kg preoperatively to 6.44 kg postoperatively. Mean
      postoperative Buck-Gramcko score was 49 (excellent); overall Kaplan-Meier
      analysis with revision as the end point showed 94% implant survivorship at a mean
      followup of 72.1 months. CONCLUSIONS: Our results are superior to those of other
      implants and support continued use of this implant. Studies with longer followup
      are required to confirm these results. LEVEL OF EVIDENCE: Level IV, therapeutic
      study. See the Guidelines for Authors for a complete description of levels of
      evidence.

PMID- 22585349
TI  - Cementing acetabular liners into secure cementless shells for polyethylene wear
      provides durable mid-term fixation.
AB  - BACKGROUND: In a previous experiment studying cementation of liners into
      cementless acetabular shells, placing grooves in the liner in a spider-web
      configuration created the greatest construct strength. Scoring shells without
      screw holes or other texturing helped prevent failure at the shell-cement
      interface. However, it was unclear whether these practices caused durable
      constructs in patients. QUESTIONS/PURPOSES: We therefore determined (1)
      rerevision rates; (2) functional scores (Harris hip scores, WOMAC, and SF-36);
      (3) acetabular loosening rates; and (4) acetabular osteolysis rates in patients
      in whom we cemented nonconstrained liners into well-fixed and well-positioned
      acetabular shells. METHODS: We prospectively followed 30 patients with 31 total
      hip arthroplasties in which a worn acetabular liner was revised by cementing a
      new liner into the existing shell that was stable and well positioned. Acetabular
      liners were prepared as determined by our previous study. Twenty-seven of the 30
      patients (28 hips) were evaluated clinically. We recorded revisions and
      determined radiographic loosening and osteolysis. The minimum clinical followup
      was 2 years (mean, 5.3 years; range, 2-10 years). Twenty-six hips (87%) had
      minimum 2-year radiographic followup with an average length of 4.8 years.
      RESULTS: No hip required rerevision during the followup interval. Two hips (6%)
      dislocated once, both treated nonoperatively. Harris hip scores, WOMAC, and SF-36
      scores increased over preoperatively at last followup. All acetabular shells and
      liners were radiographically stable without evidence of loosening or progressive
      acetabular osteolysis. CONCLUSIONS: Cementation of a liner into a well-fixed
      cementless shell after scoring in a spider-web configuration provided secure
      fixation with no failures of the construct at average 5.3 years followup. LEVEL
      OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 22585351
TI  - Cis-2-decenoic acid inhibits S. aureus growth and biofilm in vitro: a pilot
      study.
AB  - BACKGROUND: Cis-2 decenoic acid (C2DA) disperses biofilm in many strains of
      microorganisms. However, whether C2DA inhibits bacterial growth or has potential
      to boost the actions of antibiotics is unknown. QUESTIONS/PURPOSES: We asked
      whether (1) C2DA inhibited MRSA growth and biofilm, (2) antibiotics increased
      inhibitory effects, (3) inhibitory concentrations of C2DA were cytotoxic to human
      cells, and (4) effective concentrations could be delivered from a chitosan sponge
      drug delivery device. METHODS: Broth containing seven concentrations of C2DA and
      six concentrations of either daptomycin, vancomycin, or linezolid was inoculated
      with a clinical isolate of MRSA and added to a total of 504 coated microtiter
      plate wells in triplicate (n = 3) for turbidity bacterial growth and crystal
      violet biofilm mass quantification. We used fibroblast cell viability assays of
      six C2DA concentrations (n = 4) to evaluate preliminary biocompatibility. We
      measured the elution of C2DA from a chitosan sponge drug delivery device with two
      representative loading concentrations (n = 3). RESULTS: C2DA at concentrations of
      500 MUg/mL and above inhibited growth, while 125 MUg/mL C2DA inhibited biofilm.
      Combination with antibiotics increased these effects. At concentrations up to 500
      MUg/mL, there were no cytotoxic effects on fibroblasts. Chitosan sponges loaded
      with 100 mg of C2DA eluted concentrations at or above biofilm-inhibitory
      concentrations for 5 days. CONCLUSIONS: C2DA inhibited biofilm formation by MRSA
      at biocompatible concentrations, with increasing biofilm reduction with added
      antibiotics. Elution of C2DA from a chitosan sponge can be modified through
      adjusting loading concentration. CLINICAL RELEVANCE: By inhibiting biofilm
      formation on implant surfaces, C2DA may reduce the number of infections in
      musculoskeletal trauma.

PMID- 22585353
TI  - Efficient proline and prolinol ether mediated 3-component synthesis of 3- and 3,4
      substituted chromenone derivatives.
AB  - A highly efficient route for the synthesis of valuable 3,4-substituted chromenone
      derivatives by the reaction of 1,3-diketones with aldehydes in the presence of l
      proline was developed. The reactions take advantage of readily available starting
      materials and follow a Knoevenagel condensation/Michael
      addition/hemiacetalization domino process. Chiral 3-substituted chromenones are
      obtained with high enantioselectivities when a chiral diarylprolinol TMS-ether is
      applied in the reaction.

PMID- 22585352
TI  - One-screw fixation provides similar stability to that of two-screw fixation for
      type II dens fractures.
AB  - BACKGROUND: Anterior screw fixation has been widely adopted for the treatment of
      type II dens fractures. However, there is still controversy regarding whether one
      or two-screw fixation is more appropriate. QUESTIONS/PURPOSES: We addressed
      three questions: (1) Do one- and two-screw fixation techniques differ regarding
      shear stiffness and rotational stiffness? (2) Can shear stiffness and rotational
      stiffness after screw fixation be restored to normal? (3) Does stiffness after
      screw fixation correlate with bone mineral density (BMD)? METHODS: We randomly
      assigned 14 fresh axes into two groups (seven axes each): one receiving one-screw
      fixation and another receiving two-screw fixation. Shear and torsional stiffness
      were measured using a nondestructive low-load test in six directions. A
      transverse osteotomy then was created at the base of the dens and fixed using one
      or two screws. Shear and torsional stiffness were tested again under the same
      testing conditions. RESULTS: Mean stiffness in all directions after screw
      fixation was similar in both groups. The stiffness after one- and two-screw
      fixation was not restored to normal: the mean shear stiffness restored ratio was
      less than 50% and the mean torsional stiffness restored ratio was less than 6% in
      both groups. BMD did not correlate with mean stiffness after screw fixation in
      both groups. CONCLUSIONS: One- and two-screw fixation for type II dens fractures
      provide similar stability but neither restores normal shear or torsional
      stiffness. CLINICAL RELEVANCE: One-screw fixation might be used as an alternative
      to two-screw fixation. Assumed BMD should not influence surgical decision making.

PMID- 22585354
TI  - Effect of accelerated electron beam on mechanical properties of human cortical
      bone: influence of different processing methods.
AB  - Accelerated electron beam (EB) irradiation has been a sufficient method used for
      sterilisation of human tissue grafts for many years in a number of tissue banks.
      Accelerated EB, in contrast to more often used gamma photons, is a form of
      ionizing radiation that is characterized by lower penetration, however it is more
      effective in producing ionisation and to reach the same level of sterility, the
      exposition time of irradiated product is shorter. There are several factors,
      including dose and temperature of irradiation, processing conditions, as well as
      source of irradiation that may influence mechanical properties of a bone graft.
      The purpose of this study was to evaluate the effect e-beam irradiation with
      doses of 25 or 35 kGy, performed on dry ice or at ambient temperature, on
      mechanical properties of non-defatted or defatted compact bone grafts. Left and
      right femurs from six male cadaveric donors, aged from 46 to 54 years, were
      transversely cut into slices of 10 mm height, parallel to the longitudinal axis
      of the bone. Compact bone rings were assigned to the eight experimental groups
      according to the different processing method (defatted or non-defatted), as well
      as e-beam irradiation dose (25 or 35 kGy) and temperature conditions of
      irradiation (ambient temperature or dry ice). Axial compression testing was
      performed with a material testing machine. Results obtained for elastic and
      plastic regions of stress-strain curves examined by univariate analysis are
      described. Based on multivariate analysis, including all groups, it was found
      that temperature of e-beam irradiation and defatting had no consistent
      significant effect on evaluated mechanical parameters of compact bone rings. In
      contrast, irradiation with both doses significantly decreased the ultimate strain
      and its derivative toughness, while not affecting the ultimate stress (bone
      strength). As no deterioration of mechanical properties was observed in the
      elastic region, the reduction of the energy absorption capacity of irradiated
      bone rings apparently resulted from changes generated by irradiation within the
      plastic strain region.

PMID- 22585355
TI  - Induced chirality in fisetin upon binding to serum albumin: experimental circular
      dichroism and TDDFT calculations.
AB  - Theoretical absorption and electronic circular dichroism (ECD) spectra predicted
      via time-dependent density functional theory (TDDFT) calculations on the neutral
      and four anionic species of fisetin, an achiral flavonoid, were used to
      rationalize the experimental absorption and induced circular dichroism (ICD)
      spectra of the ligand upon binding to human serum albumin (HSA). On this basis,
      the mechanism responsible for the appearance of the ICD signal was ascribed to a
      distortion of the conformation of bound fisetin. Furthermore, comparison of the
      simulated and experimental spectra revealed that two fisetin species bind to HSA,
      namely, the neutral molecule and the anion deprotonated at the hydroxyl group in
      position 7, in a 1:1 ratio. The coupling of the theoretical results with the
      experimental absorption and ICD data allows identification of the flavonoid
      species that bind to the protein and evaluation of their conformation in the
      binding site.

PMID- 22585356
TI  - DFT studies on one-electron oxidation and one-electron reduction for 2- and 4
      aminopyridines.
AB  - Quantum-chemical calculations {DFT(B3LYP)/6-311+G(d,p)} were performed for all
      possible tautomers (aromatic and nonaromatic) of neutral 2- and 4-aminopyridines
      and their oxidized and reduced forms. One-electron oxidation has no important
      effect on the tautomeric preference for 2-aminopyridine. The amine tautomer is
      favored. However, oxidation increases the stability of the imine NH tautomer, and
      its contribution in the tautomeric mixture cannot be neglected. In the case of 4
      aminopyridine, one-electron oxidation increases the stability of both the amine
      and imine NH tautomers. Consequently, they possess very close energies. As major
      tautomers, they dictate the composition of the tautomeric mixture. The CH
      tautomers may be considered as very rare forms for both neutral and oxidized
      aminopyridines. A reverse situation takes place for the reduced forms of
      aminopyridines. One-electron reduction favors the C3 atom for the labile proton
      for both aminopyridines. This may partially explain the origin of the CH
      tautomers for the anionic states of nucleobases containing the exo NH(2) group.

PMID- 22585357
TI  - Acceptability, validity and reliability of the Turkish QUALIOST((r)) in
      postmenopausal women with osteoporosis.
AB  - The quality-of-life questionnaire in osteoporosis (QUALIOST((r))) is commonly
      used and accepted generic instrument in osteoporosis. This study aimed to
      translate QUALIOST((r)) into Turkish language and assess its reliability,
      validity and acceptability in women with postmenopausal osteoporosis (PMO). After
      the questionnaire was translated into Turkish, it was administered to 110 with
      PMO. The reliability studies were assessed by test-retest reliability (ICC) and
      internal consistency (Cronbach's alpha). Construct validity was assessed by using
      correlating QUALIOST((r)) with SF-36. Results showed that ICC values were 0.92,
      0.91 and 0.92, for physical domain, emotional domain and total QUALIOST((r))
      scores, respectively. Similarly, Cronbach's alpha was acceptable in all domains
      (0.85, 0.83 and 0.84, respectively). Significant moderate-to-high correlations
      were obtained between QUALIOST((r)) and SF-36 dimensions (r value between -0.39
      and -0.72, p < 0.001). Also, there were moderate-high correlations between the
      domains of questionnaire and pain intensity and disease duration (r value between
      0.35 and 0.45, p < 0.05). In conclusion, this study, which reported firstly
      psychometric properties and usefulness of the Turkish QUALIOST((r)), showed that
      it is a potentially useful measure with a high validity and reliability
      standards.

PMID- 22585358
TI  - Label-free, coupler-free, scalable and intracellular bio-imaging by multimode
      plasmonic resonances in split-ring resonators.

PMID- 22585359
TI  - Is there any association between the severity of lower urinary tract symptoms and
      the risk of biopsy-detectable prostate cancer in patients with PSA level below 20
      ng/ml in multi-core prostate biopsy?
AB  - BACKGROUND: To assess whether the severity of lower urinary tract symptoms (LUTS)
      is associated with the risk of prostate cancer (PCa) detection via a multi (>=12)
      core prostate biopsy. METHODS: From January 2004 to May 2011, 3,107 patients
      underwent transrectal ultrasound (TRUS) prostate biopsies due to elevated PSA
      levels ranging between 3 and 20 ng/ml or abnormal digital rectal exams (DREs).
      Multivariate logistic analysis was used to assess the potential association of
      LUTS and PCa detection via biopsy. The predictive accuracy of the multivariate
      model was assessed based on the receiver operating characteristics-derived area
      under the curve. RESULTS: The median International Prostate Symptom Score (IPSS)
      was 11, and the mean PSA was 6.81 ng/ml. Of the total subjects, PCa was detected
      from biopsy in 931 (30.0%) patients. In a comparison of 1,465 patients with IPSS
      >= 11 and 1,642 patients with IPSS <11, those with a higher IPSS were older, had
      higher PSA and had a larger prostate, but there were no significant differences
      in the PCa detection rates. However, in multivariate analysis incorporating other
      associated variables, a higher IPSS was significantly associated with lower odds
      of PCa detection (P = 0.016). Nevertheless, addition of the IPSS did not
      significantly increase the accuracy of the multivariate model devised for the
      detection of PCa (P = 0.098). CONCLUSIONS: Although PCa was detected less
      commonly among men with higher LUTS, LUTS may not provide additional prognostic
      information beyond that which can be obtained via previously established
      prognostic factors.

PMID- 22585361
TI  - When contributions make a difference: explaining order effects in responsibility
      attribution.
AB  - In two experiments, we established an order effect in responsibility
      attributions. In line with Spellman (Journal of Experimental Psychology: General
      126: 323-348, 1997), who proposed that a person's perceived causal contribution
      varies with the degree to which it changes the probability of the eventual
      outcome, Experiment 1 showed that in a team challenge in which the players
      contribute sequentially, the last player's blame or credit is attenuated if the
      team's result has already been determined prior to her acting. Experiment 2
      illustrated that this attenuation effect does not overgeneralize to situations in
      which the experienced order of events does not map onto the objective order of
      events; the level of the last person's performance is only discounted if that
      person knew that the result was already determined. Furthermore, Experiment 1
      demonstrated that responsibility attributions remain sensitive to differences in
      performance, even if the outcome is already determined. We suggest a theoretical
      extension of Spellman's model, according to which participants' responsibility
      attributions are determined not only by whether a contribution made a difference
      in the actual situation, but also by whether it would have made a difference had
      things turned out somewhat differently.

PMID- 22585360
TI  - Positron emission tomography imaging of endometrial cancer using engineered anti
      EMP2 antibody fragments.
AB  - PURPOSE: As imaging of the cell surface tetraspan protein epithelial membrane
      protein-2 (EMP2) expression in malignant tumors may provide important prognostic
      and predictive diagnostic information, the goal of this study is to determine if
      antibody fragments to EMP2 may be useful for imaging EMP2 positive tumors.
      PROCEDURES: The normal tissue distribution of EMP2 protein expression was
      evaluated by immunohistochemistry and found to be discretely expressed in both
      mouse and human tissues. To detect EMP2 in tumors, a recombinant human anti-EMP2
      minibody (scFv-hinge-C(H)3 dimer; 80 kDa) was designed to recognize a common
      epitope in mice and humans and characterized. In human tumor cell lines, the
      antibody binding induced EMP2 internalization and degradation, prompting the need
      for a residualizing imaging strategy. Following conjugation to DOTA (1,4,7,10
      tetraazacyclododecane-N,N',N',N'"-tetraacetic acid), the minibody was
      radiolabeled with (64)Cu (t (1/2) = 12.7 h) and evaluated in mice as a positron
      emission tomography (PET) imaging agent for human EMP2-expressing endometrial
      tumor xenografts. RESULTS: The residualizing agent, (64)Cu-DOTA anti-EMP2
      minibody, achieved high uptake in endometrial cancer xenografts overexpressing
      EMP2 (10.2 +/- 2.6, percent injected dose per gram (%ID/g) +/- SD) with moderate
      uptake in wild-type HEC1A tumors (6.0 +/- 0.1). In both cases, precise tumor
      delineation was observed from the PET images. In contrast, low uptake was
      observed with anti-EMP2 minibodies in EMP2-negative tumors (1.9 +/- 0.5).
      CONCLUSIONS: This new immune-PET agent may be useful for preclinical assessment
      of anti-EMP2 targeting in vivo. It may also have value for imaging of tumor
      localization and therapeutic response in patients with EMP2-positive
      malignancies.

PMID- 22585362
TI  - Consequences of restudy choices in younger and older learners.
AB  - Allowing young learners to exert metacognitive control over learning often
      improves memory performance; however, little research has examined the
      consequences of giving older adults control over learning. In this study, younger
      and older adults studied word pairs before choosing half of the word pairs for
      restudy. Learners either restudied the items they chose (in the honor condition)
      or the items they did not choose (the dishonor condition; Kornell & Metcalfe,
      Journal of Experimental Psychology: Learning, Memory, and Cognition 32:609-622,
      2006). Older and younger learners chose the same types of items for restudy, but
      the effectiveness of these choices differed greatly by age. For young learners,
      memory was superior in the honor condition, but older learners actually revealed
      numerically higher performance in the dishonor condition. This reveals a dramatic
      failure of metacognitive control, in the absence of any obvious monitoring
      deficit, in older adults. Implications for models of self-regulated learning are
      discussed.

PMID- 22585363
TI  - Current technologies for biological treatment of textile wastewater--a review.
AB  - The release of colored wastewater represents a serious environmental problem and
      public health concern. Color removal from textile wastewater has become a big
      challenge over the last decades, and up to now, there is no single and
      economically attractive treatment method that can effectively decolorize the
      wastewater. Effluents from textile manufacturing, dyeing, and finishing processes
      contain high concentrations of biologically difficult-to-degrade or even inert
      auxiliaries, chemicals like acids, waxes, fats, salts, binders, thickeners, urea,
      surfactants, reducing agents, etc. The various chemicals such as biocides and
      stain repellents used for brightening, sequestering, anticreasing, sizing,
      softening, and wetting of the yarn or fabric are also present in wastewater.
      Therefore, the textile wastewater needs environmental friendly, effective
      treatment process. This paper provides a critical review on the current
      technology available for decolorization and degradation of textile wastewater and
      also suggests effective and economically attractive alternatives.

PMID- 22585364
TI  - Characterization of xerophytic thermophilic laccase exhibiting metal ion
      dependent dye decolorization potential.
AB  - Five laccase enzyme isoforms were isolated and purified to homogeneity from the
      cladodes of xerophytic Cereus pterogonus and Opuntia vulgaris plant species.
      Catalytic activity of all isoforms was enhanced 40 % by 1 mM Cu(2+) and 1 mM
      Mn(2+), whereas the activity was inhibited 100 % by 10 mM Fe(2+). Enzyme was
      found stable in 4 M urea and exhibited inactivity of 50 % in 8 M urea
      concentration. Ethylenediaminetetraacetic acid and cysteine-HCl were able to
      completely inhibit the enzyme activity at 1 mM and 100 MUM, respectively.
      Preheated enzyme samples showed enhanced and stable catalytic activity in the
      presence of divalent cations over a period of 30 min compared with controls. In
      the presence of metal ions (1 mM Cu(2+) and 1 mM Mn(2+)), the preheated enzyme
      forms (60-90  degrees C) achieved 97 % of Malachite green and 98.75 % of Indigo
      blue (both at 2 %, w/v) dye decolorization in 12 h.

PMID- 22585365
TI  - A rapid and simple method for preparing an insoluble substrate for screening of
      microbial xylanase.
AB  - Several types of enzymes, including cellulases and xylanases, are required to
      degrade hemicelluloses and cellulose, which are major components of
      lignocellulosic biomass. Such degradative processes can be used to produce
      various useful industrial biomaterials. Screening methods for detecting
      polysaccharide-degrading microorganisms include the use of dye-labeled substrates
      in growth medium and culture plate staining techniques. However, the preparation
      of screening plates, which typically involves chemical cross-linking to
      synthesize a dye-labeled substrate, is a complicated and time-consuming process.
      Moreover, such commercial substrates are very expensive, costing tenfold more
      than the natural xylan. Staining methods are also problematic because they may
      damage relevant microorganisms and are associated with contamination of colonies
      of desirable organisms with adjacent unwanted bacteria. In the present study, we
      describe a sonication method for the simple and rapid preparation of an insoluble
      substrate that can be used to screen for xylanase-expressing bacteria in
      microbial populations. Using this new method, we have successfully isolated a
      novel xylanase gene from a xylolytic microorganism termed Xyl02-KBRB and Xyl14
      KBRB in the bovine rumen.

PMID- 22585366
TI  - A model of the lateral line of fish for vortex sensing.
AB  - In this paper, the lateral line trunk canal (LLTC) of a fish is modeled to
      investigate how it is affected by an external flow field. Potential flow theory
      is adopted to model the flow field around a fish's body in the presence of a
      Karman vortex street. Karman and reverse Karman streets represent the flow
      patterns behind a bluff body and a traveling fish, respectively. An analytical
      solution is obtained for a flat body, while a fish-like body is modeled using a
      Joukowski transformation and the corresponding equations are solved numerically.
      The pressure distribution on the body surface is then computed employing
      Bernoulli's equation. For a known external flow, the flow inside the LLTC is
      driven by the pressure gradient between a pair of consecutive pores, which can be
      solved analytically. Governing dimensionless parameters are obtained from this
      analytical solution, and the effects of these numbers on the amplitude or
      features of the velocity distribution inside the canal are studied. The results
      show that the main characteristics of a vortex street including the magnitude of
      vortices, their translational speed, their spacing, their distance from the
      fish's body and the angle of the vortex street axis can all be recovered by
      measuring the velocity distribution along the canal and its changes with time. To
      this end, the proposed LLTC model could explain how a fish identifies the
      characteristics of a Karman vortex street shed by a nearby object or a traveling
      fish. It is also demonstrated that while this model captures the ac (alternating
      current) component of the external velocity signal, the dc (direct current)
      component of the signal is filtered out. Based on the results of our model, the
      role of the LLTC in a fish's schooling and its evolutionary impact on fish
      sensing are discussed.

PMID- 22585367
TI  - Salivary gland pathology as a new finding in Treacher Collins syndrome.
AB  - In our clinical experience, individuals with Treacher Collins syndrome (TCS)
      present with more complaints of oral dryness and higher caries activity than seen
      in the general population. A literature review identified no reports of salivary
      gland pathology and glandular dysfunction associated with TCS. Twenty-one
      Norwegian individuals with TCS underwent ultrasound examinations and salivary
      secretion tests of the submandibular and parotid glands. Intraglandular
      architecture patterns were analyzed and subsequently classified as either normal,
      dysplastic, or aplastic. The results were compared with salivary secretion rates
      and subjective reports of oral dryness. Ultrasound examination revealed
      pathological appearance of the salivary glands in approximately half (48%) of the
      individuals, with dysplasia identified in six (29%) participants and aplasia in
      four (19%). Almost all participants had co-existing low salivary secretion rates.
      A few individuals had low salivary secretion rates despite normal appearance of
      the salivary gland tissue on ultrasound examination. Subjective experience of
      oral dryness did not correlate significantly with low salivary secretion rates.
      We conclude that mild to severe salivary gland pathology and dysfunction can be
      associated with TCS. Further investigation is needed to clarify this association.

PMID- 22585369
TI  - Central venous catheters in premature babies: radiological evaluation,
      malpositioning and complications.
AB  - Central venous catheters are important in the care for prematurely born children
      in the neonatal intensive care unit. The purpose of this pictorial essay is to
      illustrate correct positioning, malpositioning and possible complications of such
      devices.

PMID- 22585370
TI  - Doubly phenoxo-hydroxo-bridged dicopper(II) complexes: individual contributions
      of the bridges to antiferromagnetic coupling based on two related biomimetic
      models for catechol oxidases.
AB  - This paper describes the synthesis, structure and spectroscopic and magnetic
      properties of two (MU-phenoxo)(MU-hydroxo)dicopper(II) complexes (1 and 2) which
      contain similar N,O-donor atoms but with distinct coordination arrangements
      around the Cu(II) centers. Structural and magnetic studies of 1 and 2 allowed us
      to evaluate, for the first time, the individual contributions of the {Cu(MU
      phenoxo)Cu} and {Cu(MU-hydroxo)Cu} structural units to the antiferromagnetic
      coupling between the Cu(II) centers in these complexes.

PMID- 22585368
TI  - Characterization of molten globule PopB in absence and presence of its chaperone
      PcrH.
AB  - The TTSS encoding "translocator operon" of Pseudomonas aeruginosa consists of a
      major translocator protein PopB, minor translocator protein PopD and their
      cognate chaperone PcrH. Far-UV CD spectra and secondary structure prediction
      servers predict an alpha-helical model for PopB, PcrH and PopB-PcrH complex. PopB
      itself forms a single species of higher order oligomer (15 mer) as seen from AUC,
      but in complex with PcrH, both monomeric (1:1) and oligomeric form exist. PopB
      has large solvent-exposed hydrophobic patches and exists as an unordered molten
      globule in its native state, but on forming complex with PcrH it gets transformed
      into an ordered molten globule. Tryptophan fluorescence spectrum indicates that
      PopB interacts with the first TPR region of dimeric PcrH to form a stable PopB
      PcrH complex that has a partial rigid structure with a large hydrodynamic radius
      and few tertiary contacts. The pH-dependent studies of PopB, PcrH and complex by
      ANS fluorescence, urea induced unfolding and thermal denaturation experiments
      prove that PcrH not only provides structural support to the ordered molten
      globule PopB in complex but also undergoes conformational change to assist PopB
      to pass through the needle complex of TTSS and form pores in the host cell
      membrane. ITC experiments show a strong affinity (K(d) ~ 0.37 MUM) of PopB for
      PcrH at pH 7.8, which reduces to ~0.68 MUM at pH 5.8. PcrH also loses its rigid
      tertiary structure at pH 5 and attains a molten globule conformation. This
      indicates that the decrease in pH releases PopB molecules and thus triggers the
      TTSS activation mechanism for the formation of a functional translocon.

PMID- 22585371
TI  - Sinusoidal echo-planar imaging with parallel acquisition technique for reduced
      acoustic noise in auditory fMRI.
AB  - PURPOSE: To extend the parameter restrictions of a silent echo-planar imaging
      (sEPI) sequence using sinusoidal readout (RO) gradients, in particular with
      increased spatial resolution. The sound pressure level (SPL) of the most feasible
      configurations is compared to conventional EPI having trapezoidal RO gradients.
      MATERIALS AND METHODS: We enhanced the sEPI sequence by integrating a parallel
      acquisition technique (PAT) on a 3 T magnetic resonance imaging (MRI) system. The
      SPL was measured for matrix sizes of 64 * 64 and 128 * 128 pixels, without and
      with PAT (R = 2). The signal-to-noise ratio (SNR) was examined for both
      sinusoidal and trapezoidal RO gradients. RESULTS: Compared to EPI PAT, the SPL
      could be reduced by up to 11.1 dB and 5.1 dB for matrix sizes of 64 * 64 and 128
      * 128 pixels, respectively. The SNR of sinusoidal RO gradients is lower by a
      factor of 0.96 on average compared to trapezoidal RO gradients. CONCLUSION: The
      sEPI PAT sequence allows for 1) increased resolution, 2) expanded RO frequency
      range toward lower frequencies, which is in general beneficial for SPL, or 3)
      shortened TE, TR, and RO train length. At the same time, it generates lower SPL
      compared to conventional EPI for a wide range of RO frequencies while having the
      same imaging parameters.

PMID- 22585373
TI  - Miconazole nitrate oral disintegrating tablets: in vivo performance and stability
      study.
AB  - The interest in and need for formulating miconazole nitrate (MN), a broad
      spectrum antifungal, as an oral disintegrating tablet for treatment of some forms
      of candidiasis have increased. Formulation of MN in this dosage form will be more
      advantageous, producing dual effect: local in the buccal cavity and systemic with
      rapid absorption. Four formulations were prepared utilizing the foam granulation
      technique. The prepared tablets were characterized by measuring the weight
      uniformity, thickness, tensile strength, friability, and drug content. In
      addition, tablet disintegration time, in vitro dissolution, and in vivo
      disintegration time were also evaluated. Stability testing for the prepared
      tablets under stress and accelerated conditions in two different packs were
      investigated. Each pack was incubated at two different elevated temperature and
      relative humidity (RH), namely 40 +/- 2 degrees C/75 +/- 5% RH and 50 +/- 2
      degrees C/75 +/- 5% RH. The purpose of the study is to monitor any degradation
      reactions which will help to predict the shelf life of the product under the
      defined storage conditions. Finally, in vivo study was performed on the most
      stable formula to determine its pharmacokinetic parameters. The results revealed
      that all the prepared tablets showed acceptable tablet characteristics and were
      stable under the tested conditions. The most stable formula was that containing
      magnesium stearate as lubricant, hydrophobic Aerosil R972 as glidant, low urea
      content, mannitol/microcrystalline cellulose ratio 2:1, and 9% Plasdone XL100 as
      superdisintegrant. The in vivo results revealed that the tested formula showed
      rapid absorption compared to the physical blend (t (max) were 1 and 4 h,
      respectively), while the extent of absorption was almost the same.

PMID- 22585372
TI  - Design of experiments-based monitoring of critical quality attributes for the
      spray-drying process of insulin by NIR spectroscopy.
AB  - Moisture content and aerodynamic particle size are critical quality attributes
      for spray-dried protein formulations. In this study, spray-dried insulin powders
      intended for pulmonary delivery were produced applying design of experiments
      methodology. Near infrared spectroscopy (NIR) in combination with preprocessing
      and multivariate analysis in the form of partial least squares projections to
      latent structures (PLS) were used to correlate the spectral data with moisture
      content and aerodynamic particle size measured by a time of flight principle. PLS
      models predicting the moisture content were based on the chemical information of
      the water molecules in the NIR spectrum. Models yielded prediction errors (RMSEP)
      between 0.39% and 0.48% with thermal gravimetric analysis used as reference
      method. The PLS models predicting the aerodynamic particle size were based on
      baseline offset in the NIR spectra and yielded prediction errors between 0.27 and
      0.48 MUm. The morphology of the spray-dried particles had a significant impact on
      the predictive ability of the models. Good predictive models could be obtained
      for spherical particles with a calibration error (RMSECV) of 0.22 MUm, whereas
      wrinkled particles resulted in much less robust models with a Q (2) of 0.69.
      Based on the results in this study, NIR is a suitable tool for process analysis
      of the spray-drying process and for control of moisture content and particle
      size, in particular for smooth and spherical particles.

PMID- 22585374
TI  - A study on in-line tablet coating--the influence of compaction and coating on
      tablet dimensional changes.
AB  - Prior to coating, tablets are usually stored for a definite period to enable
      complete strain recovery and prevent subsequent volumetric expansion-related
      coating defects. In-line coating is defined as the coating of tablets immediately
      after compaction. In-line coating will be expected to improve manufacturing
      efficiencies. In this study, the possibility of in-line coating was studied by
      evaluating the influence of compaction and coating on tablet dimensional changes.
      The use of tapered dies for compaction was also evaluated. Two types of tablet
      coaters which presented different coating environments, namely the SupercellTM
      coater and pan coater, were employed for coating. The extent of tablet
      dimensional changes was studied in real time using optical laser sensors in a
      controlled environment. After compaction, tablet dimensional changes were found
      to be anisotropic. In contrast, coating resulted in isotropic volume expansion in
      both the axial and radial directions. Pan coating resulted in significantly
      greater tablet dimensional changes compared to SupercellTM coating. There was no
      significant difference in dimensional changes of tablets coated in line or after
      complete viscoelastic strain recovery for SupercellTM coating. However,
      significantly different dimensional changes were observed for pan coating. The
      use of tapered dies during compaction was found to result in more rapid
      viscoelastic strain recovery and also significantly reduced tablet dimensional
      changes when tablets were immediately coated after compaction using the pan
      coater. In conclusion, the SupercellTM coater appeared to be more suitable for in
      line tablet coating, while tapered dies were beneficial in reducing tablet
      dimensional changes when the pan coater was employed for in-line coating.

PMID- 22585375
TI  - Mechanically induced amorphization of drugs: a study of the thermal behavior of
      cryomilled compounds.
AB  - The purpose of this work was to determine what aspect of the milled compound
      influences its thermal profile. For this, six different compounds with different
      properties were chosen and cryomilled for different times to get an amorphous
      solid. Differential scanning calorimetry (DSC) and X-ray powder diffraction were
      used to characterize the material and look at the thermal behavior. Melt-quenched
      samples were also prepared, and the thermal profile upon milling was determined
      and correlated with the thermal behavior of the cryomilled samples. Growth rates
      were determined by hot-stage microscopy. Ketoconazole, when cryomilled, showed
      only one crystallization exotherm in the DSC profile. Ursodiol, and to some
      extent indomethacin, initially showed a double exotherm which eventually become a
      single exotherm on further milling. Griseofulvin, carbamazepine, and piroxicam
      exhibited a double exotherm in the DSC profile upon cryomilling to the amorphous
      state. Surface crystal growth rates around T (g) were found to be highest for
      compounds showing the double exotherm in the DSC. Thus, it was seen that
      compounds which have high surface crystallization tendency will exhibit the
      double exotherm during heating.

PMID- 22585376
TI  - Effect of polacrilin potassium as disintegrant on bioavailability of diclofenac
      potassium in tablets : a technical note.
AB  - Polacrilin potassium is an ion exchange resin used in oral pharmaceutical
      formulations as a tablet disintegrant. It is a weakly acidic cation exchange
      resin. Chemically, it is a partial potassium salt of a copolymer of methacrylic
      acid with divinyl benzene. It ionizes to an anionic polymer chain and potassium
      cations. It was hypothesized that polacrilin potassium may be able to improve the
      permeability of anionic drugs according to the Donnan membrane phenomenon. The
      effect of polacrilin potassium on the permeability of diclofenac potassium, used
      as a model anionic drug, was tested in vitro using diffusion cells and in vivo by
      monitoring serum levels in rats. The amount of drug permeated across a dialysis
      membrane in vitro was significantly more in the presence of polacrilin potassium.
      Significant improvement was found in the extent of drug absorption in vivo. It
      could be concluded that polacrilin potassium may be used as a high-functionality
      excipient for improving the bioavailability of anionic drugs having poor
      gastrointestinal permeability.

PMID- 22585377
TI  - The original sin of cognitive science.
AB  - Classical cognitive science was launched on the premise that the architecture of
      human cognition is uniform and universal across the species. This premise is
      biologically impossible and is being actively undermined by, for example, imaging
      genomics. Anthropology (including archaeology, biological anthropology,
      linguistics, and cultural anthropology) is, in contrast, largely concerned with
      the diversification of human culture, language, and biology across time and space
      it belongs fundamentally to the evolutionary sciences. The new cognitive sciences
      that will emerge from the interactions with the biological sciences will focus on
      variation and diversity, opening the door for rapprochement with anthropology.

PMID- 22585378
TI  - The effect of a postoperative course of oral prednisone on postoperative
      morbidity following childhood tonsillectomy.
AB  - OBJECTIVE: Tonsillectomy is a common procedure with a wide range of described
      operative techniques and usage of perioperative medications. Single-dose
      intraoperative dexamethasone has been shown to decrease postoperative nausea and
      pain and improve return to normal diet. The aim was to determine if a course of
      oral postoperative steroids would further decrease postoperative morbidity
      following tonsillectomy in children. STUDY DESIGN: Randomized, placebo
      controlled, double-blinded trial. Power analysis recommended 198 participants.
      SETTING: A university hospital and private hospital. SUBJECTS AND METHODS: The
      authors compared a 5-day course of oral prednisolone with placebo in a pediatric
      population (3-16 years) undergoing tonsillectomy to assess effects on
      postoperative pain, nausea, and vomiting and return to normal function. They also
      assessed the effect of corticosteroids on sleep duration and aspects of sleep
      quality. RESULTS: The results showed no significant difference between the 2
      groups when analyzed for differences in the above variables both overall and at
      each of the postoperative 10 time points (pain, P = .478; nausea and vomiting, P
      = .556; return to normal diet well, P = .234; return to normal activity, P =
      .668; bedtime, P = .056; number of times awake during the night, P = .593).
      CONCLUSION: There is no evidence of benefit from postoperative administration of
      corticosteroids in pediatric patients recovering from tonsillectomy.

PMID- 22585379
TI  - Reconditioning of ceramic orthodontic brackets with an Er,Cr:YSGG laser.
AB  - It is now known that erbium lasers are effective in composite removal, but there
      is minimal information about their efficacy on recycling of ceramic brackets.
      This study, therefore, aimed to determine the percentage of remaining adhesive on
      the base and the shear bond strength of debonded ceramic brackets after being
      reconditioned by an Er,Cr:YSGG (erbium, chromium: yttrium-scandium-gallium
      garnet) laser. Thirty premolars were divided into three groups, then bonded with
      mechanical retention ceramic brackets according to the bracket base conditions:
      (1) new brackets; (2) debonded brackets cleaned of adhesive with the Er,Cr:YSGG
      laser at 3.5 W; and (3) debonded brackets cleaned of adhesive with the Er,Cr:YSGG
      laser at 4 W. Before bonding, the percentage of remaining adhesive on the bases
      of reconditioned brackets was calculated by using stereomicroscopic images
      through an image processing software. The brackets were then tested in shear mode
      in a universal testing machine and the adhesive remnant index scores were
      determined. The percentage of remaining adhesive on the bases of brackets that
      were cleaned by the Er,Cr:YSGG laser at 4 W (3.1 %) was significantly lower than
      that of the 3.5-W laser group (5.9 %) (p = 0.03). No significant difference was
      found in bond strengths between the new and the reconditioned brackets (p =
      0.19). The frequency of bond failure at the enamel-adhesive interface was lower
      in the laser-reconditioned brackets when compared to the new brackets. The
      application of Er,Cr:YSGG laser was efficient in removing adhesive from bases of
      debonded ceramic brackets because it produced comparable bond strengths to new
      brackets while reducing the risk of enamel damage during debonding.

PMID- 22585380
TI  - Mechanical properties of composite resins light-cured using a blue DPSS laser.
AB  - Lasers have many favorable features as a light source owing to their
      monochromaticity and coherence. This study examined the mechanical properties of
      composite resins that were light-cured using a diode-pumped solid state (DPSS)
      laser. Eight composite resins were light-cured using four different light sources
      (one quartz-tungsten-halogen (QTH), two light-emitting diodes (LEDs), and one
      DPSS laser with a wavelength of 473 nm). The light intensity of the DPSS laser
      and remaining light-curing units were approximately 500 and 900 mW/cm(2),
      respectively. The microhardness, flexural properties, and compressive properties
      were evaluated using the Vickers hardness test, three-point bending test, and
      compression test, respectively. In most cases, the microhardness, flexural
      properties, and compressive properties of the specimens light-cured using the
      DPSS laser were similar to those obtained using the other light-curing units.
      Within the limits of the study, the microhardness, flexural modulus, and
      compressive strength were linearly correlated with the filler content (in weight
      percent). The flexural modulus and compressive modulus were also linearly
      correlated with the microhardness. Even with a much lower light intensity, the
      DPSS laser with a wavelength of 473 nm can polymerize composite resins and give
      comparable mechanical properties to those obtained using the other light-curing
      units.

PMID- 22585381
TI  - Influence of the hydration state on the ultrashort laser ablation of dental hard
      tissues.
AB  - Since about 40 years, laser-based surgical tools have been used in medicine and
      dentistry to improve clinical protocols. In dentistry, femtosecond lasers have
      been claimed to be a potential ablation tool. It would, however, be good to
      perform a more fundamental investigation to understand ablation interaction
      mechanisms and possible side effects, depending on different specific components
      of the target tissue. The goal of this study is to show the changes of ablation
      characteristics in the femtosecond regime at different levels of structural water
      within dental hard tissues. Thirty human teeth samples were split into three
      hydration groups and subdivided into dentin and enamel groups (n = 5). The
      specimens were irradiated using a 70-fs Ti:sapphire laser (with a 1-kHz
      repetition rate and a 801-nm wavelength output). Ablation was performed using
      five different power levels and three exposure times. The results clearly show an
      inversely proportional dependence of the ablation threshold to the hydration
      level of the tissues. A known mathematical model was adapted in order to include
      the influence of the changes on the relative fractional composition of dental
      hard tissues. This analysis was consistent with the experimental results
      regarding the ablation threshold. High thermal and mechanical damages were
      observed as a high repetition rate had been applied. Macroscopic images and
      scanning electron microscopy images were used to preliminarily analyze both the
      thermal and mechanical damage thresholds, and their variations according to the
      hydration level present. By manipulating the hydration states, the modifications
      in the proportions of the molecules that build dental hard tissues clearly shift,
      and therefore, the characteristics of a plasma-induced ablation change.

PMID- 22585382
TI  - The effects of Photofrin-mediated photodynamic therapy on the modulation of EGFR
      in esophageal squamous cell carcinoma cells.
AB  - Photodynamic therapy (PDT) has been demonstrated to be an effective minimally
      invasive treatment modality for early esophageal cancer. However, the molecular
      action in esophageal cancer during PDT is hardly known. EGFR has been known to
      downregulate in various cancer cells during PDT. In this study, we investigated
      the effects of Photofrin-mediated PDT on cell death and expression of EGFR in
      CE48T/VGH (CE48T) esophageal squamous cell carcinoma cells. We found that the
      photosensitizer Photofrin in the absence of light exposure can downregulate the
      expression of EGFR at both transcription and translation levels. Higher
      concentrations of Photofrin results in cytotoxicity whereas lower doses of
      Photofrin inhibit EGFR expression under dark control without inducing significant
      cell death. This Photofrin-associated inhibition of EGFR was repeated in lung
      cancer, cervical cancer, and glioblastoma cells. Another esophageal squamous cell
      carcinoma cell line CE81T/VGH (CE81T) was found to be resistant to Photofrin
      induced inhibition of EGFR as well as to Photofrin-mediated dark toxicity
      compared with CE48T. The resistance to the cytotoxicity in CE81T cells became
      insignificant when the Photofrin-treated cells were further irradiated by red
      light (Photofrin-PDT). We suggest Photofrin modulates the expression of EGFR in
      cancer cells. However, efficient cell death still requires the combination of
      Photofrin and light irradiation in esophageal squamous cell carcinoma cells.

PMID- 22585383
TI  - Cell-type specific interferon stimulated gene staining in liver underlies
      response to interferon therapy in chronic HBV infected patients.
AB  - BACKGROUND: Interferon-alpha is approved as one of the main therapeutic
      treatments for chronic hepatitis B virus infection, but only a small number of
      patients achieve sustained virological response. The molecular mechanisms
      underlying IFN-alpha resistance in those patients who do not respond remain
      elusive. Previous work in our laboratory identified the pre-activation of IFN
      signaling leading to increased expression of a subset of interferon stimulated
      genes in the pretreatment liver tissues of chronic HBV infected patients
      correlated with treatment non-response. AIMS: We studied the cell-type specific
      gene expression of interferon stimulated genes in the liver of chronic HBV
      infected patients and the cellular basis of the phenotype through ISG15 and MxA
      protein expression. METHODS: Immunohistochemical analysis was used to detect the
      expression of ISG15 and MxA protein in the pretreatment liver tissues of chronic
      HBV infected patients and the expression patterns were correlated with treatment
      outcomes. RESULTS: In the non-responders, ISG15 and MxA protein expression in the
      pretreatment liver tissues was more pronounced in hepatocytes while in the
      responders, ISG15 and MxA protein expression was more focused in macrophages.
      ISG15 and MxA proteins were occasionally expressed in hepatocytes in normal
      livers. CONCLUSION: There were significant differences in the cell-type specific
      protein expression of ISG15 and MxA in the pretreatment liver tissues of chronic
      HBV infected patients between treatment responders and non-responders. An easy
      prediction method based on immunohistochemical stains of a subset of interferon
      stimulated genes may be developed to predict treatment outcomes of IFN therapy in
      chronic HBV infected patients.

PMID- 22585385
TI  - Interstate migration has fallen less than you think: consequences of hot deck
      imputation in the current population survey.
AB  - We show that much of the recent reported decrease in interstate migration is a
      statistical artifact. Before 2006, the Census Bureau's imputation procedure for
      dealing with missing data in the Current Population Survey inflated the estimated
      interstate migration rate. An undocumented change in the procedure corrected the
      problem starting in 2006, thus reducing the estimated migration rate. The change
      in imputation procedures explains 90% of the reported decrease in interstate
      migration between 2005 and 2006, and 42% of the decrease between 2000 (the recent
      high-water mark) and 2010. After we remove the effect of the change in
      procedures, we find that the annual interstate migration rate follows a smooth
      downward trend from 1996 to 2010. Contrary to popular belief, the 2007-2009
      recession is not associated with any additional decrease in interstate migration
      relative to trend.

PMID- 22585384
TI  - Combination of radiofrequency ablation with transarterial chemoembolization for
      hepatocellular carcinoma: a meta-analysis.
AB  - BACKGROUND: Recent studies suggest that the combination of radiofrequency
      ablation (RFA) and transarterial chemoembolization (TACE) may have a synergistic
      effect for hepatocellular carcinoma (HCC). AIMS: The aim of this meta-analysis
      was to compare the effectiveness of combination of RFA and TACE with that of RFA
      alone in patients with HCC. METHODS: Randomized controlled trials and
      retrospective cohort studies comparing RFA plus TACE with RFA alone for HCC were
      included into this meta-analysis. Study quality was rated with a standardized
      scale and the strength of evidence was also rated by using the grading of
      recommendations assessment, development, and evaluation system (GRADE system).
      RESULTS: Meta-analyses showed that the combination of RFA and TACE was obviously
      associated with higher survival rates (odds ratio [OR](1-year) = 2.14, 95 %
      confidence interval [95 % CI] 1.57-2.91, P < 0.001; OR(3-year) = 1.98, 95 % CI
      1.28-3.07, P = 0.001; OR(5-year) = 2.70, 95 % CI 1.42-5.14, P = 0.003). The
      overall quality of evidence was judged to be low by using the GRADE system.
      CONCLUSIONS: The combination of TACE with RFA can improve the overall survival
      rate and provides better prognosis for patients with HCC, but more randomized
      controlled trials using large sample size are needed to provide sufficient
      evidence.

PMID- 22585386
TI  - Use of PCA3 in detecting prostate cancer in initial and repeat prostate biopsy
      patients.
AB  - BACKGROUND: The PCA3 urinary assay has shown promise in predicting the presence
      of prostate cancer. We evaluated the value of this test in patients undergoing
      initial and repeat prostate biopsy. METHODS: PCA3 and PSA levels were obtained
      from 456 men with no known personal history of prostate cancer prior to prostate
      biopsy. Two hundred eighty-nine men underwent an initial prostate biopsy and 167
      underwent a repeat prostate biopsy. PCA3 and PSA levels were compared to the
      prostate biopsy results. RESULTS: PCA3 score was shown to be independent of
      prostate volume (P = 0.162) and PSA level (P = 0.959). PCA3 scores were
      significantly higher in patients with cancer on prostate biopsy compared to
      patients with negative biopsy results (P < 0.0001). In logistic regression, PCA3
      showed a significantly higher AUC than PSA (0.726 vs. 0.512, P = 0.0001). This
      difference persisted when examining the initial biopsy subgroup, with PCA3 out
      performing PSA (AUC 0.772 vs. AUC = 0.552, P < 0.0001), but not in the repeat
      biopsy subgroup (AUC = 0.605 vs. AUC = 0.500, P = 0.2488). CONCLUSIONS: PCA3 was
      found to be a better predictor of prostate cancer than PSA in the total
      population as well as the initial biopsy population, but was not superior to PSA
      in the repeat biopsy population. Prostate 73: 48-53, 2013. (c) 2012 Wiley
      Periodicals, Inc.

PMID- 22585387
TI  - Effects of oxidative stress on immunosuppression induced by selenium deficiency
      in chickens.
AB  - Selenium (Se) is an important nutritional trace element possessing immune
      stimulatory properties. The aim of this 75-day study was to investigate effect of
      oxidative stress on immunosuppression induced by selenium deficiency by
      determining antioxidative function, morphological changes, DNA damage, and immune
      function in immune organ of chickens. One hundred sixty 1-day-old chickens (egg
      type birds) were randomly assigned to two groups of 80 each and were fed on a low
      Se diet (0.032 mg/kg Se) or a control diet (0.282 mg/kg Se, sodium selenite),
      respectively. Se contents in blood and immune organ (thymus, spleen, bursa of
      Fabricius) were determined on days 30, 45, 60, and 75, respectively.
      Antioxidative function was examined by total antioxidant capacity (T-AOC),
      superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and xanthine oxidase
      (XOD), and oxidative damage was examined by malondialdehyde (MDA) detection. DNA
      damage was measured by comet assay, and immune function was examined by
      determining serum interleukin-1beta (IL-1beta), interleukin-2 (IL-2), and tumor
      necrosis factor (TNF) contents. The results showed that Se concentrations in the
      low-Se group were significantly lower (P < 0.05) than in the control group. Low
      Se diet caused a decrease in the activities of T-AOC, SOD, GSH-Px, and an
      increase in XOD activity and MDA content. Pathological lesions and DNA damage of
      immune tissues were observed in low-Se group, while the serum IL-1beta and IL-2
      contents decreased, and TNF content increased. The present study demonstrated
      that chickens fed deficient in Se diets exhibited lesions in immune organs,
      decreased serum IL-1beta, IL-2 content, and serum TNF content, indicating that
      oxidative stress inhibited the development of immune organs and finally impaired
      the immune function of chickens.

PMID- 22585388
TI  - Sonographic diagnosis of fetal intestinal volvulus with ileal atresia: a case
      report.
AB  - Fetal intestinal volvulus is a rare life-threatening condition usually
      manifesting after birth with most cases being associated with intestinal
      malrotation. It appears on prenatal sonography (US) as a twisting of the bowel
      loops around the mesenteric artery, leading to mechanical obstruction and
      ischemic necrosis of the bowel. We report a case of intrauterine intestinal
      volvulus with ileal atresia, suspected when US revealed a typical "whirlpool"
      sign at 37 weeks' gestation, with a segment of markedly distended bowel loops and
      small amount of fetal ascites.

PMID- 22585389
TI  - Walking the walk while thinking about the talk: embodied interpretation of
      metaphorical narratives.
AB  - Two sets of experiments examined people's embodied understanding of metaphorical
      narratives. Participants heard one of two stories about a romantic relationship;
      either one that was successful or one that was not, that initially described it
      in metaphorical terms as "Your relationship was moving along in a good direction"
      or nonmetaphorical terms as "Your relationship was very important to you."
      Participants were then blindfolded and attempted to accurately walk, or imagine
      walking, to a marker 40 feet away while they thought about the story they just
      heard. People who heard about the successful metaphorical story walked longer and
      further than those presented with the unsuccessful relationship story. But these
      walking and imagining differences disappeared when the critical metaphorical
      statement "moving along in a good direction" was replaced by a nonmetaphorical
      expression. These findings, and those from another set of experiments, suggest
      that people's understanding of metaphorical narratives is partly based on their
      embodied simulations of the metaphorical actions referred to in these stories.

PMID- 22585390
TI  - Potential of ultrafiltration for organic matter removal in the polymer industry
      effluent based on particle size distribution analysis.
AB  - The purpose of the study was the experimental evaluation of ultrafiltration as a
      potential innovative technology for the removal of organic matter of around
      15,000 mg chemical oxygen demand (COD) per liter in the polymer industry
      wastewater. Particle size distribution (PSD) analysis served as the major
      experimental instrument along with conventional chemical settling. Biodegradation
      characteristics of the remaining COD after ultrafiltration were determined by
      model interpretation of the corresponding oxygen uptake rate (OUR) profile. The
      study first involved a detailed characterization of the polymer wastewater
      including PSD analysis of the COD content. Chemical treatability was investigated
      using lime alone and with ferric chloride as coagulants followed with a PSD
      assessment of the chemically settled effluent. Modeling of the OUR profile
      generated by the ultrafiltration effluent defined related biodegradation kinetics
      and provided information on the overall COD removal potential. PSD analysis
      indicated that more than 70 % of the total COD accumulated in the 220- to 450-nm
      size range. It indicated that ultrafiltration was potentially capable of removing
      more than 90 % of the COD with an effluent lower than 1,500 mg COD/L. Chemical
      settling with 750 mg/L of FeCl(3) dosing at a pH of 7.0 provided a similar
      performance. The ultrafiltration effluent included mainly hydrolysable COD and
      proved to be biodegradable, with the process kinetics compatible with domestic
      sewage. PSD evaluation proved to be a valuable scientific instrument for
      underlining the merit of ultrafiltration as the appropriate innovative technology
      for polymer wastewater, removing the major portion of the COD in a way that is
      suitable for recovery and reuse and producing a totally biodegradable effluent.

PMID- 22585391
TI  - Characterization, sources, and potential risk assessment of PAHs in surface
      sediments from nearshore and farther shore zones of the Yangtze estuary, China.
AB  - The assessment of polycyclic aromatic hydrocarbons (PAHs) contamination in
      surface sediments from the Yangtze estuary which is a representative area
      affected by anthropogenic activity (rapid industrialization, high-population
      density, and construction of dams upstream) in the world was systematically
      conducted. Fifty-one samples were analyzed by high-performance liquid
      chromatography (HPLC). The ?PAHs in all sediments varied from 76.9 to 2,936.8 ng
      g(-1). Compared with other estuaries in the world, the PAH levels in the Yangtze
      estuary are low to moderate. Phenanthrene, acenaphthylene, fluoranthene, and
      pyrene were relatively abundant. The ?PAH levels and composition varied obviously
      in different estuarine zones due to different sources. The highest ?PAHs
      concentration was observed in the nearshore of Chongming Island. The PAH
      composition showed that four to six ring PAHs were mainly found in the nearshore
      areas, while two to three ring PAHs were in the farther shore zones. The PAHs in
      the Yangtze estuary were derived primarily from combustion sources. A mixture of
      petroleum combustion and biomass combustion mainly from coal combustion and
      vehicle emission was the main source of PAHs from the nearshore areas, while the
      spill, volatilization, or combustion of petroleum from shipping process and
      shoreside discharge were important for PAHs in the farther shore areas. The
      result of potential ecotoxicological risk assessment based on sediment quality
      guidelines indicated low PAH ecological risk in the Yangtze estuary. The study
      could provide foundation for the protection of water quality of the Yangtze
      estuary by inducing main sources input.

PMID- 22585392
TI  - Oxidative stress and lipid peroxidation in the earthworm Eisenia fetida induced
      by low doses of fomesafen.
AB  - Formesafen is a diphenyl ether herbicide that has adverse effects on non-target
      animals. However, knowledge about the effect of fomesafen on the antioxidant
      defense system in earthworms is vague. Thus, it is essential to investigate the
      effects of fomesafen on the antioxidant defense system in earthworms as a
      precautionary method. In the present study, earthworms (Eisenia fetida) were
      exposed to artificial soil treated with a range of concentrations of fomesafen
      (0, 10, 100, and 500 MUg kg(-1)) and were collected on the 3rd, 7th, 14th, 21st,
      and 28th days of exposure. Subsequently, the antioxidant enzyme activities
      (superoxide dismutase (SOD); catalase (CAT); and guaiacol peroxidase (POD)),
      reactive oxygen species (ROS) level, and malondialdehyde (MDA) content due to
      fomesafen treatment were examined in earthworms. Compared with the control, the
      SOD activity increased on the third and seventh days but decreased on the 14th
      day due to treatment with 100 and 500 MUg kg(-1) of fomesafen. The activities of
      CAT and POD increased significantly on the third, seventh, and 14th days of
      exposure. In addition, the ROS level was significantly enhanced throughout the
      entire experimental period and showed a statistically dose-dependent relationship
      on the seventh and 14th days. The MDA content markedly increased on the seventh
      day of exposure; however, obvious changes were not detected at other exposure
      period. Low doses of fomesafen (<= 500 MUg kg(-1)) may result in oxidative damage
      and lipid peroxidation in E. fetida by inducing the generation of ROS at short
      exposure periods (14 days). However, the adverse effects of fomesafen gradually
      disappear as the cooperation of antioxidant enzymes and exposure time are
      prolonged. This result may be helpful for further studies on the toxicological
      mechanisms of fomesafen to earthworms.

PMID- 22585395
TI  - Aging in Prader-Willi syndrome: twelve persons over the age of 50 years.
AB  - The life expectancy of persons with Prader-Willi syndrome (PWS) has increased in
      recent years. Because of the paucity of reports on older persons with PWS, the
      natural history, the onset, and type of age-related problems are poorly
      understood. Twelve persons with a genetically confirmed diagnosis of PWS aged
      over 50 years are described (4 deletion; 8 mUPD). Data on physical, behavioral,
      psychiatric, and aging characteristics were collected through semi-structured
      interviews with the individuals with PWS and their main carers. Cardiovascular
      diseases, diabetes, dermatological, and orthopedic problems were common physical
      complaints in older people with PWS. Functioning in activities of daily living,
      psychological functioning, physical functions, and care dependence were
      substantially worse in the older age group (50+) compared to the control group
      (18-49 years). Seven out of eight persons with mUPD had a history of psychiatric
      illness. Behavioral problems were observed in the older age group. Given the
      combination of age-related physical morbidity, physical appearance, behavioral
      and psychiatric problems, and functional decline in our cohort, we hypothesize
      that premature aging occurs in PWS. The care for older people with PWS requires a
      lifespan approach that recognizes the presence, progression, and consequences of
      specific morbidity. Special medical surveillance of people with PWS from 40 years
      onwards would ensure that intervention and support is offered with respect to
      specific areas of decline at the earliest possible time.

PMID- 22585396
TI  - Preliminary observations and diagnostic value of lipid peak in ovarian
      thecomas/fibrothecomas using in vivo proton MR spectroscopy at 3T.
AB  - PURPOSE: To retrospectively evaluate the significance of lipid peak in in vivo
      proton magnetic resonance (MR) spectroscopy for the diagnosis of ovarian
      thecomas/fibrothecomas in patients with solid gynecologic tumors exhibiting
      totally or partially low signal intensity on T2-weighted images. MATERIALS AND
      METHODS: MR spectroscopy was performed in patients with pathologically diagnosed
      gynecologic tumors at 3T MRI. Single-voxel MR spectroscopy data were collected
      from a single square volume of interest that encompassed the gynecologic masses.
      The lipid concentration level was classified into three classes (high; low;
      none). RESULTS: A total of 20 gynecologic tumors in 20 patients were evaluated in
      this study. High lipid peak was observed in all seven thecomas/fibrothecomas,
      whereas low lipid peak was observed in only one fibroma in 13 nonthecomatous
      tumors (six benign ovarian tumors and seven subserosal uterine leiomyomas). The
      presence of lipid peak for the diagnosis of thecomas/fibrothecomas had a
      sensitivity of 100%, specificity of 92%, positive predictive value of 88%, and
      negative predictive value of 100%. CONCLUSION: The high lipid peak reflecting
      abundant intracellular lipid contents is considered a specific metabolite
      concentration for thecomas/fibrothecomas. Demonstration of high lipid peak may
      contribute to the diagnosis of thecomas/fibrothecomas in distinguishing from
      other benign ovarian fibrous tumors or subserosal uterine leiomyomas.

PMID- 22585397
TI  - Nonequilibrium perturbation theory in Liouville-Fock space for inelastic electron
      transport.
AB  - We use a superoperator representation of the quantum kinetic equation to develop
      nonequilibrium perturbation theory for an inelastic electron current through a
      quantum dot. We derive a Lindblad-type kinetic equation for an embedded quantum
      dot (i.e. a quantum dot connected to Lindblad dissipators through a buffer zone).
      The kinetic equation is converted to non-Hermitian field theory in Liouville-Fock
      space. The general nonequilibrium many-body perturbation theory is developed and
      applied to the quantum dot with electron-vibronic and electron-electron
      interactions. Our perturbation theory becomes equivalent to a Keldysh
      nonequilibrium Green's function perturbative treatment provided that the buffer
      zone is large enough to alleviate the problems associated with approximations of
      the Lindblad kinetic equation.

PMID- 22585398
TI  - miR-9 enhances IL-2 production in activated human CD4(+)  T cells by repressing
      Blimp-1.
AB  - The fast production of effector cytokines, such as IL-2, is essential for the
      autocrine function in the rapid activation of naive CD4(+)  T cells. Here, we
      show that the microRNA (miRNA) pathway plays an important role in the
      posttranscriptional regulation of proinflammatory cytokines in human CD4(+)  T
      cells. miRNAs are small noncoding molecules that act as posttranscriptional
      regulators of gene expression by binding to the 3' untranslated region of target
      mRNAs. Using microarray and deep sequencing approaches, we detected an increase
      in the abundance of miR-9 in activated human CD4(+)  T cells. To determine the
      impact of miR-9 on immune responses, we analyzed its effect on two putative
      target genes, PRDM1, which encodes for the transcription factor Blimp-1 (B
      lymphocyte-induced maturation protein-1), and Bcl-6 (B cell lymphoma-6 protein).
      Suppression of miR-9 led to increased expression of PRDM1 and Bcl-6, which
      subsequently resulted in diminished secretion of IL-2 and IFN-gamma. Our data
      provide evidence that the abundance of Blimp-1, and consequently the secretion of
      proinflammatory cytokines, is regulated in two ways: (i) transcriptional
      regulation by activation of CD4(+)  T cells and (ii) posttranscriptional
      regulation by enhanced miR-9 expression.

PMID- 22585400
TI  - Is fetal magnetic resonance imaging indicated when ultrasound isolated mild
      ventriculomegaly is present in pregnancies with no risk factors?
AB  - OBJECTIVE: Ventriculomegaly (VM) is the most common brain anomaly in prenatal
      ultrasound (US) diagnosis. There is a general trend to perform fetal magnetic
      resonance imaging (MRI) when VM is severe (greater than 15 mm) and/or it is not
      isolated. The role of MRI is debated when VM is borderline (between 10 and 15 mm)
      and isolated. Some authors have subdivided borderline VM into mild (10 to 12 mm)
      and moderate (>12 to 15 mm). The aim of the study was to evaluate the role of MR
      in the imaging protocol of fetal cases characterized by mild isolated VM and no
      risk factors. METHOD: As a retrospective study, 179 fetal MRI exams (mean
      gestational age: 26 weeks), performed for mild, isolated VM on US, were analyzed
      to search additional or different findings with respect to ultrasound. The
      potential impact of MRI results on prenatal counselling is described. RESULTS: In
      49/179 cases, MRI and US results differed, but only in two of these cases did MRI
      studies provide clinically consistent additional information. In 130/179 cases,
      MRI confirmed US findings. CONCLUSION: In this extremely selected group of
      fetuses with isolated, mild VM and no risk factors, MRI may not be indicated in
      the prenatal imaging protocol.

PMID- 22585399
TI  - Telomerase gene therapy in adult and old mice delays aging and increases
      longevity without increasing cancer.
AB  - A major goal in aging research is to improve health during aging. In the case of
      mice, genetic manipulations that shorten or lengthen telomeres result,
      respectively, in decreased or increased longevity. Based on this, we have tested
      the effects of a telomerase gene therapy in adult (1 year of age) and old (2
      years of age) mice. Treatment of 1- and 2-year old mice with an adeno associated
      virus (AAV) of wide tropism expressing mouse TERT had remarkable beneficial
      effects on health and fitness, including insulin sensitivity, osteoporosis,
      neuromuscular coordination and several molecular biomarkers of aging.
      Importantly, telomerase-treated mice did not develop more cancer than their
      control littermates, suggesting that the known tumorigenic activity of telomerase
      is severely decreased when expressed in adult or old organisms using AAV vectors.
      Finally, telomerase-treated mice, both at 1-year and at 2-year of age, had an
      increase in median lifespan of 24 and 13%, respectively. These beneficial effects
      were not observed with a catalytically inactive TERT, demonstrating that they
      require telomerase activity. Together, these results constitute a proof-of
      principle of a role of TERT in delaying physiological aging and extending
      longevity in normal mice through a telomerase-based treatment, and demonstrate
      the feasibility of anti-aging gene therapy.

PMID- 22585401
TI  - Soil microarthropod communities from Mediterranean forest ecosystems in Central
      Italy under different disturbances.
AB  - The aim of this study is to assess soil quality in Mediterranean forests of
      Central Italy, from evergreen to deciduous, with different types of management
      (coppice vs. high forest vs. secondary old growth) and compaction impacts
      (machinery vs. recreational). Soil quality was evaluated studying soil
      microarthropod communities and applying a biological index (QBS-ar) based on the
      concept that the higher is the soil quality, the higher will be the number of
      microarthropod groups well adapted to the soil habitat. Our results confirm that
      hardwood soils are characterised by the highest biodiversity level among
      terrestrial communities and by a well-structured and mature microarthropod
      community, which is typical of stable ecosystems (QBS value, >200). While
      silvicultural practices and forest composition do not seem to influence QBS-ar
      values or microarthropod community structure, the index is very efficient in
      detecting soil impacts (soil compaction due to logging activities). Several taxa
      (Protura, Diplura, Coleoptera adults, Pauropoda, Diplopoda, Symphyla, Chilopoda,
      Diptera larvae and Opiliones) react negatively to soil compaction and degradation
      (QBS value, <150). In particular, Protura, Diplura, Symphyla and Pauropoda, are
      taxonomic groups linked to undisturbed soil. This index could also be a useful
      tool in monitoring soil biodiversity in protected areas and in urban forestry to
      prevent the negative effects of trampling. QBS-ar is a candidate index for
      biomonitoring of soil microarthropod biodiversity across the landscape to provide
      guidance for the sustainable management of renewable resource and nature
      conservation.

PMID- 22585402
TI  - Remote sensing and GIS-based integrated analysis of land cover change in Duzce
      plain and its surroundings (north western Turkey).
AB  - The aim of this study is to research natural land cover change caused by the
      permanent effects of human activities in Duzce plain and its surroundings, and to
      determine the current status of the land cover. For this purpose, two Landsat TM
      images were used in the study for the years 1987 and 2010. These images are
      analysed by using data image processing techniques in ERDAS Imagine(c)10.0 and
      ArcGIS(c)10.0 software. Land cover change nomenclature is classified according to
      the Coordination of Information on the Environment Level 2 Classification (1-
      urban fabric, 2--industrial, commercial and transport units, 3--heterogeneous
      agricultural areas, 4--forests, and 5--inland wetlands). Furthermore, the image
      analysis results are confirmed by the field research. According to the results, a
      decrease of 33.5 % was recorded in forest areas from 24,840.7 to 16,529.0 ha; an
      increase of 11.2 % was recorded in heterogeneous agricultural areas from 47,702.7
      to 53,051.7 ha. Natural vegetation, which is the large part of land cover in the
      research area, has been changing rapidly because of rapid urbanisation and
      agricultural activities. As a result, it is concluded that significant changes
      have occurred on the natural land cover between the years 1987 and 2010 in the
      Duzce plain and its surroundings.

PMID- 22585403
TI  - Spatial variability of air pollutants in the city of Taranto, Italy and its
      potential impact on exposure assessment.
AB  - Epidemiological studies typically use monitored air pollution data from a single
      station or as averaged data from several stations to estimate population
      exposure. In industrialized urban areas, this approach may present critical
      issues due to the spatial complexities of air pollutants which are emitted by
      different sources. This study focused on the city of Taranto, which is one of the
      most highly industrialized cities in southern Italy. Epidemiological studies have
      revealed several critical situations in this area, in terms of mortality excess
      and short-term health effects of air pollution. The aims of this paper are to
      study the variability of air pollutants in the city of Taranto and to interpret
      the results in relation to the applicability of the data in assessing population
      exposure. Meteorological and pollution data (SO2, NO2, PM10), measured
      simultaneously and continuously during the period 2006-2010 in five air quality
      stations, were analyzed. Relative and absolute spatial concentration variations
      were investigated by means of statistical indexes. Results show significant
      differences among stations. The highest correlation between stations was observed
      for PM10 concentrations, while critical values were found for NO2. The worst
      values were observed for the SO2 series. The high values of 90th percentile of
      differences between pairs of monitoring sites for the three pollutants index
      suggest that mean concentrations differ by large amounts from site to site. The
      overall analysis supports the hypothesis that various parts of the city are
      differently affected by the different emission sources, depending on
      meteorological conditions. In particular, analysis revealed that the influence of
      the industrial site may be primarily identified with the series of SO2 data which
      exhibit higher mean concentration values and positive correlations with wind
      intensity when the monitoring station is downwind from the industrial site.
      Results suggest evaluating the population exposure to air pollutants in
      industrialized cities by taking into account the possible zones of influence of
      different emission sources. More research is needed to identify an indicator,
      which ought to be a synthesis of several pollutants, and take into account the
      meteorological variables.

PMID- 22585404
TI  - Spatio-temporal changes in agrochemical inputs and the risk assessment before and
      after the Grain-For-Green Policy in China.
AB  - China's Grain-For-Green Policy (GFGP) of returning marginal cropland to forest or
      grassland is one of the most important large-scale initiatives to combat land
      degradation in its ecologically vulnerable regions. In order to maintain and
      increase crop production from decreasing areas of cropland, substantial spatio
      temporal changes in agrochemical inputs have occurred, which have strongly
      influenced the ecological and environmental status of land in China. Based on the
      agrochemical inputs (chemical fertilizer, pesticide, plastic sheeting, and
      agricultural diesel oil) at the provincial level between 1993 and 2009, cluster
      analysis and gravity center modeling were used to trace these spatio-temporal
      changes. A regional comparative study was also undertaken to investigate the
      changes in the relative size of agrochemical inputs in the eastern, central, and
      western regions of China. It was found that the agrochemical inputs increased
      considerably at the nation level after the GFGP, which in order of increasing
      rate were: plastic sheeting > agricultural diesel oil > pesticide > chemical
      fertilizer. The gravity centers of agrochemical inputs moved substantially
      towards the northwest or west during the latter period of GFGP and regional
      comparative analysis showed that the agrochemical inputs increased substantially
      in the western region between 2004 and 2009. The ecological degradation caused by
      the expansion of the area devoted to crop production in the western region and
      the potential risk of agricultural non-point pollution caused by the increasing
      agrochemical inputs are the main factors restricting this area's sustainable
      development.

PMID- 22585405
TI  - Invariant natural killer T cells are not affected by lysosomal storage in
      patients with Niemann-Pick disease type C.
AB  - Invariant natural killer T (iNKT) cells are a specialised subset of T cells that
      are restricted to the MHC class I like molecule, CD1d. The ligands for iNKT cells
      are lipids, with the canonical superagonist being alpha-galactosylceramide, a non
      mammalian glycosphingolipid. Trafficking of CD1d through the lysosome is required
      for the development of murine iNKT cells. Niemann-Pick type C (NPC) disease is a
      lysosomal storage disorder caused by dysfunction in either of two lysosomal
      proteins, NPC1 or NPC2, resulting in the storage of multiple lipids, including
      glycosphingolipids. In the NPC1 mouse model, iNKT cells are virtually
      undetectable, which is likely due to the inability of CD1d to be loaded with the
      selecting ligand due to defective lysosomal function and/or CD1d trafficking.
      However, in this study we have found that in NPC1 patients iNKT cells are present
      at normal frequencies, with no phenotypic or functional differences. In addi
      tion, antigen-presenting cells derived from NPC1 patients are functionally
      competent to present several different CD1d/iNKT-cell ligands. This further
      supports the hypothesis that there are different trafficking requirements for the
      development of murine and human iNKT cells, and a functional lysosomal/late
      endosomal compartment is not required for human iNKT-cell development.

PMID- 22585406
TI  - Quantitative assessment of bone marrow attenuation values at MDCT: an objective
      tool for the detection of bone bruise related to occult sacral insufficiency
      fractures.
AB  - OBJECTIVES: To prove the feasibility of using Hounsfield attenuation values at
      MDCT to detect bone bruises related to sacral insufficiency fractures. METHODS:
      Twenty-two patients with acute sacrum trauma and no fracture findings at MDCT
      were included in our prospective study. Two observers independently reviewed CTs
      regarding visual signs of bone bruises in 132 defined regions of the sacral alae.
      Interobserver agreement was tested by kappa statistics. Subsequently, HU values
      were obtained in the same regions, and attenuation differences between the two
      sides were calculated. Validity and reliability were assessed by intraclass
      correlation coefficient and Bland-Altman analysis. HU differences were subjected
      to ROC curve analysis to determine sensitivity, specificity, PPV and NPV. MRI
      served as standard reference. RESULTS: MRI revealed 19 regions with bone bruises
      and associated sacral insufficiency fractures. HU measurements demonstrated good
      validity and reliability (r = 0.989). ROC curve analysis exhibited an ideal
      cutoff value of 35.7 HU density difference between affected and non-affected
      regions. Visual evaluation revealed moderate agreement (kappa = 0.48); diagnostic
      accuracy was inferior to objective evaluation. CONCLUSIONS: Assessment of
      differences in bone marrow density by HU measurements is an objective and
      reliable tool for detection of bone bruises associated with occult sacral
      insufficiency fractures. KEY POINTS : * Bone bruising is associated with occult
      sacral insufficiency fractures. * Assessment of differences in bone marrow CT
      attenuation appears valid and reliable. * Comparative HU measurements of bone
      marrow allow detection of bone bruises. * Comparative HU measurements have high
      specificity and negative predictive values. * Comparative HU measurements may
      make further diagnostic workup with MRI unnecessary.

PMID- 22585407
TI  - The value of visfatin in the prediction of metabolic syndrome: a multi-factorial
      analysis.
AB  - We describe the adipokine concentration in patients with metabolic syndrome,
      stressing the role of visfatin. A cross-sectional single center study on 70
      patients with metabolic syndrome plus 76 controls was performed. Patients with
      metabolic syndrome had higher visfatin levels compared to controls, following
      adjustments for age, sex, waist/hip circumference, systolic, and diastolic blood
      pressure, fasting plasma glucose (FPG), HbA1c, body mass index, and homeostasis
      model assessment of insulin resistance (HOMA-IR) [(5.39 +/- 0.29 vs. 3.88 +/-
      0.32); F(1, 129) = 10.8, P < 0.01]. A logistic regression analysis revealed that
      circulating visfatin levels and HbA1c were the top variables for predicating
      metabolic syndrome. In patients with metabolic syndrome, visfatin did not
      correlate with any of the measured variables, with the single exception of
      adiponectin; in patients without metabolic syndrome, circulating visfatin levels
      were significantly associated with FPG, HbA1c, insulin, HOMA-IR, HDL, and
      triglyceride. These findings may contribute to our current knowledge about
      visfatin in metabolic syndrome.

PMID- 22585410
TI  - 31st Annual Conference of the International Society for Clinical Biostatistics.
      Preface.

PMID- 22585408
TI  - Cancer cachexia and anabolic interventions: a case report.
AB  - BACKGROUND: Standard-of-care (SOC) cancer treatments are primarily aimed at
      reducing size and progression of a tumor. There is a need for successful
      supplemental anabolic therapies to combat cancer cachexia in addition to these
      SOC treatment modalities. Anabolic interventions, including testosterone and
      amino acid supplements, may be beneficial in reducing and/or reversing muscle
      wasting in these patient populations. METHODS: A 48-year-old Caucasian female
      with recurrent cervical cancer was scheduled to receive three 21-day cycles of
      cisplatin and topetecan chemotherapy. She qualified, consented, and enrolled into
      a blinded interventional pilot study where she received daily whey protein (10 g,
      three times per day with meals) and a weekly injection of testosterone enanthate
      (100 mg intramuscular) before and during the SOC chemotherapy treatment period.
      Body composition, serum inflammatory markers, mixed muscle protein synthesis and
      breakdown rates, physical function, fatigue, and quality of life were assessed
      before and after the intervention period. RESULTS: Body composition, as assessed
      by an increase in body weight and lean body mass and reduction in fat mass;
      physical function; fatigue; and quality of life each improved across the entire
      intervention period despite general increases in inflammatory markers and no
      improvements in muscle protein turnover towards the end of the intervention.
      CONCLUSIONS: Concomitant treatment of oral amino acids and testosterone may be a
      viable therapeutic option for fighting cachexia and improving body composition
      and quality of life during chemotherapeutic treatment of recurrent cervical
      cancer. These positive outcomes may be attainable over time despite overall poor
      inflammatory status.

PMID- 22585411
TI  - 'Optimum threshold estimation based on cost function in a multistate diagnostic
      setting' by K. Skaltsa, L. Jover, D. Fuster and J. L. Carrasco.

PMID- 22585409
TI  - Novel miRNAs in the control of arsenite levels in rice.
AB  - In a species, the miRNA repertoire comprises many lineage- or species-specific
      miRNAs. Using deep sequencing, the whole transcriptome of seedling roots was
      studied and a total of 18 novel miRNAs in indica rice Minghui 86 were identified.
      Among these novel miRNAs six were up-regulated and two were down-regulated under
      arsenite stress. Quantitative real-time RT-PCR analysis revealed that miR6254 was
      predominantly expressed in roots relative to other tissues, whereas miR6250 and
      miR169i-3p were constitutively expressed in all tissues examined, with high
      abundance in roots (miR6250) or leaves (miR169i-3p). The miR6250 and miR169i-3p
      miRNAs also exhibited distinct expression patterns in rice cultivars Minghui 86
      and Nipponbare at different time points after arsenite treatment. The predicted
      targets for these miRNAs included some protein kinases, DNA, or ATP-binding
      proteins. Besides arsenite, the expression of targets of miR6250 and miR6254 was
      also up- or down-regulated in response to abiotic environmental stresses,
      indicative of their involvement in regulation of plant adaptation. Three types of
      cis-elements involved in hormone, light, and stress response were found to occur
      frequently in the promoter regions. Interestingly, miR6254 was originally
      characterized to be an exonic miRNA located in the exon of AK101391, supporting
      the notion that miRNAs may also originate from some exons in plants.

PMID- 22585412
TI  - Antiangiogenic effects of p-coumaric acid in human endothelial cells.
AB  - p-Coumaric acid, a hydroxy derivative of cinnamic acid, has been known to possess
      antioxidant and anticancer activities. Despite its potential contribution to
      chemopreventive effects, the mechanism by which p-coumaric acid exerts its
      antiangiogenic actions remains elusive. In this study, we revealed that p
      coumaric acid inhibited the sprouting of endothelial cells in rat aortic rings
      and inhibited the tube formation and migration of endothelial cells. We observed
      that p-coumaric acid could downregulate mRNA expression levels of the key
      angiogenic factors vascular endothelial growth factor and basic fibroblast growth
      factor. Also, we demonstrated that p-coumaric acid inhibited both the AKT and ERK
      signaling pathways, which are known to be crucial for angiogenesis. Using a mouse
      model, we also showed that p-coumaric acid effectively suppressed tumor growth in
      vivo by lowering hemoglobin contents. Collectively, these findings indicate that
      p-coumaric acid possesses potent anticancer properties due to the inhibition of
      angiogenesis in vivo.

PMID- 22585414
TI  - Wiedemann-Rautenstrauch syndrome: report of a variant case.
AB  - Wiedemann-Rautenstrauch syndrome (WRS) is a rare autosomal recessive disorder
      that includes premature aging phenotype at birth. The condition is also known as
      a neonatal progeroid syndrome. Up to now only a few published case reports have
      been documented. The syndrome is characterized by progeroid appearance, decreased
      subcutaneous fat, hypotrichosis, macrocephaly, and in some natal teeth. We
      describe a new patient with features of bilaterally pelvicalyceal ectasia and
      partial syndactyly on 2th and 3th toes, not previously described, to our
      knowledge.

PMID- 22585413
TI  - Urinary JCV-DNA testing during natalizumab treatment may increase accuracy of PML
      risk stratification.
AB  - The risk of progressive multifocal leukoencephalopathy (PML) in patients treated
      with natalizumab for multiple sclerosis (MS) is a serious concern. The presence
      of anti-JC virus antibodies is a risk factor for PML development, but 2.5 % of
      the patients result falsely-negative, while the prognostic relevance of testing
      JCV-DNA in biological fluids of treated patients is debated. Aim of this work was
      to evaluate the utility of testing JCV-DNA, together with anti-JCV antibodies, in
      biological samples of treated patients as a tool for PML risk stratification. 126
      subjects from 5 MS Centers in Italy were included in the study. We performed a
      cross-sectional study in 63 patients testing JCV-DNA in blood, peripheral blood
      cells and urine. We longitudinally assessed the presence of JCV-DNA in a cohort
      of 33 subjects, one of which developed PML. We could test retrospectively serum
      samples from another PML case occurred during natalizumab therapy. Anti-JCV
      antibodies and urinary JCV-DNA were both tested in 73 patients. No changes in JCV
      DNA status occurred during natalizumab treatment. The subject who developed PML
      in the longitudinal cohort had detectable JCV-DNA in urine at all time-points
      while serum or blood from both PML patients were always negative before the onset
      of disease and, in one case, after. Four subjects with JCV-DNA in urine and
      undetectable anti-JCV antibodies were retested for anti-JCV antibodies and three
      out of four resulted positive. In conclusion, testing JCV-DNA in urine is
      complementary to testing anti-JCV antibodies in identifying patients at risk of
      PML.

PMID- 22585415
TI  - Effects of Bacillus preparations on immunity and antioxidant activities in grass
      carp (Ctenopharyngodon idellus).
AB  - This experiment was conducted to study the effects of Bacillus preparations on
      immunity and antioxidant activities in grass carp. A total of 315 grass carp,
      with similar initial weight (average weight of fish 45 g), were randomly divided
      into three groups with three replicates. The control group was fed the basal diet
      without Bacillus; treatment group 1 was added Bacillus preparation no. 1 with 1 *
      10(8) cfu/m(3) per 7 days in culture water and also fed the basal diet; treatment
      group 2 was fed the basal diet mixed with 0.5 % Bacillus preparation no. 2, and
      the culture water was added 1 * 10(8) cfu/m(3) Bacillus preparation no. 1 per 7
      days. After 4 weeks of culture, 12 grass carp from each replicate were taken
      randomly for the determination of immune response and oxidization resistance
      indices. The results showed that compared with control, the level of globulin and
      IgM of treatment group 2 was significantly increased (P < 0.05), which was also
      significantly higher (P < 0.05) than that of group 1. For the non-specific
      immunity index, compared with control, the lysozyme activity and complement (C3)
      content of treatment group 1 significantly increased (P < 0.05), and the level of
      myeloperoxidase and C3 of treatment group 2 was significantly higher (P < 0.05)
      than that of control, which was also significantly higher (P < 0.05) than that of
      group 1. In the serum, compared with the control, the level of total antioxidant
      activity (T-AOC), antisuperoxide anion free radical (ASAFR) and glutathione (GSH)
      of two treatment groups was significantly increased (P < 0.05); GSH content of
      treatment group 2 was significantly (P < 0.05) higher than that of treatment
      group 1 and control. There was no significant difference between T-AOC and ASAFR
      among the two treatment groups; no significant effect was found on glutathione
      peroxidase (GSH-Px) and maleic dialdehyde (MDA) among the three groups. In the
      liver, T-AOC, SOD, ASAFR, GSH-Px and GSH from two treatment groups were
      significantly higher (P < 0.05) than those of control; T-AOC, SOD and catalase
      from treatment group 2 were significantly higher (P < 0.05) than those of
      treatment group 1; and MDA of two treatment groups was significantly decreased (P
      < 0.05) as compared with the control. The results indicate that Bacillus
      preparations added into water can increase serum immunoglobulin levels and most
      of non-specific immune parameters content and enhance the antioxidant ability of
      grass carp, while adding Bacillus preparation into the water and feed is much
      better.

PMID- 22585416
TI  - Purinergic receptors and regulatory volume decrease in seabream (Sparus aurata)
      hepatocytes: a videometric study.
AB  - The response of isolated hepatocytes of Sparus aurata to hypotonic stress was
      studied by the aid of videometric methods with the aim to investigate the
      possible involvement of ATP in the regulatory volume decrease (RVD). This study
      confirms our previous observations showing the ability of these cells to undergo
      RVD. In addition, it shows that the homeostatic response was inhibited by
      apyrase, an ATP scavenger, thus suggesting the involvement of extracellular ATP
      in the RVD response. Experiments performed in the presence of ATPgammaS or
      adenosine, agonists of P(2) and P(1) receptors respectively, and in the presence
      of suramin or 8-PT, antagonists of P(2) and P(1) receptors respectively, suggest
      that ATP exerts its stimulatory effect on the homeostatic response by interacting
      with P(2) receptors. On the other hand, the activation of P(1) receptors by ATP
      metabolites produces opposite effects. In an attempt to clarify the mechanisms
      involved in ATP release from the cell, we performed some experiments with known
      inhibitors of the possible mechanisms of regulated ATP release. The results we
      obtained let us to suppose that the mechanism allowing the exit of ATP from the
      cell is verapamil sensitive suggesting the involvement of the P-glycoprotein.

PMID- 22585417
TI  - Ontogeny of the digestive tract in butter catfish Ompok bimaculatus (Bloch)
      larvae.
AB  - The ontogeny of the digestive tract was studied histologically in butter catfish
      Ompok bimaculatus from hatching to 30 days post-hatching (dph). At hatching, the
      digestive tract of butter catfish consisted of a straight tube with a smooth
      lumen dorsally attached to the yolk sac. Between 1 and 2 dph, the mouth opened,
      oral valves were visible and canine-like teeth and taste buds were detected.
      During this period, intestine was differentiated into the anterior and posterior
      intestine, and the digestive accessory glands were also developed. Exogenous
      feeding started at 2 dph, and there was a 2-day mixed endogenous-exogenous
      feeding period. Most of the yolk sac reserves were consumed between 2 and 3 dph,
      and by 5 dph, the yolk sac was completely depleted and no longer visible in
      histological sections. Between 3 and 4 dph, several vacuoles (neutral lipids)
      were observed in the intestine and also in hepatocytes, indicating a functional
      absorption of nutrients from food. At 8 dph, differentiation of gastric glands
      was noticed, and by 9-11 dph, there were abundant gastric tubular glands arranged
      along numerous longitudinal folds. During the same period, pyloric sphincter
      appeared as an epithelial fold that separated the stomach from the anterior
      intestine. From 12 dph to the end of the study at 30 dph, no noticeable
      histological modifications were observed. The development of gastric glands is
      considered as the last major events in digestive tract development and their
      presence designates the end of larval period and the onset of the juvenile
      period. Hence, it is suggested that, butter catfish larvae have a morphologically
      complete digestive tract by 12 dph. These findings on the development of the
      digestive system in butter catfish may lead to a better understanding of the
      ontogeny and would be useful to improve the larval rearing techniques of this
      promising catfish species for freshwater aquaculture diversification.

PMID- 22585418
TI  - Readout of superconducting flux qubit state with a Cooper pair box.
AB  - We study a readout scheme of a superconducting flux qubit state with a Cooper
      pair box as a transmon. The qubit states consist of the superpositions of two
      degenerate states where the charge and phase degrees of freedom are entangled.
      Owing to the robustness of the transmon against external fluctuations, our
      readout scheme enables the quantum non-demolition and single-shot measurement of
      flux qubit states. The qubit state readout can be performed by using the
      nonlinear Josephson amplifiers after a pi/2 rotation driven by an ac electric
      field.

PMID- 22585419
TI  - Intraendosomal flow cytometry: a novel approach to analyze the protein
      composition of antigen-loaded endosomes.

PMID- 22585420
TI  - Trends in antihypertensives use among Moroccan patients.
AB  - PURPOSE: In this study, we analyzed the consumption trends of antihypertensives
      in Morocco during the 1991-2010 period and the impacts after the institution of
      Mandatory Health Insurance and the marketing of generic drugs. METHODS: We used
      sales data from the Moroccan subsidiary of IMS Health "Intercontinental Marketing
      Service". The consumption volumes were converted into defined daily doses (DDDs).
      RESULTS: Between 1991 and 2010, outpatient consumption of antihypertensives went
      from 4.37 to 23.14 DDD/1000 inhabitants/day, a 5.30-fold increase. In 2010,
      calcium channel blockers (CCBs) and angiotensin converting enzyme inhibitors
      (ACEI) were the most consumed (4.97 DDD/1000 inhabitants/day) for each one,
      followed by diuretics (4.20 DDD/1000 inhabitants/day). The most consumed products
      were amlodipine (4.27 DDD/1000 inhabitants/day) followed by ramipril (3.18
      DDD/1000 inhabitants /day) and indapamide (1.72 DDD/1000inhabitants/day). Between
      1991 and 2010, the consumption of generic antihypertensives went from 2% to 46%.
      CONCLUSION: Antihypertensive consumption increased between 1991 and 2010.
      However, despite the increase of generic drugs consumption, the levels of
      antihypertensive consumption remain lower than the needs of hypertensive
      patients.

PMID- 22585421
TI  - Unlike CD4+ T-cell help, CD28 costimulation is necessary for effective primary
      CD8+ T-cell influenza-specific immunity.
AB  - The importance of costimulation on CD4(+)  T cells has been well documented.
      However, primary CTLs against many infections including influenza can be
      generated in the absence of CD4(+)  T-cell help. The role of costimulation under
      such "helpless" circumstances is not fully elucidated. Here, we investigated such
      a role for CD28 using CTLA4Ig transgenic (Tg) mice. To ensure valid comparison
      across the genotypes, we showed that all mice had similar naive precursor
      frequencies and similar peak viral loads. In the absence of help, viral clearance
      was significantly reduced in CTLA4Ig Tg mice compared with WT mice. CD44(+)
      BrdU(+) influenza-specific CD8(+)  T cells were diminished in CTLA4Ig Tg mice at
      days 5 and 8 postinfection. Adoptive transfer of ovalbumin-specific transgenic
      CD8(+)  T cells (OT-I)-I cells into WT or CTLA4Ig Tg mice revealed that loss of
      CD28 costimulation resulted in impairment in OT-I cell division. As shown
      previously, neither viral clearance nor the generation of influenza-specific
      CD8(+)  T cells was affected by the absence of CD4(+)  T cells alone. In
      contrast, both were markedly impaired by CD28 blockade of "helpless" CD8(+)  T
      cells. We suggest that direct CD28 costimulation of CD8(+)  T cells is more
      critical in their priming during primary influenza infection than previously
      appreciated.

PMID- 22585422
TI  - The marine mammal dive response is exercise modulated to maximize aerobic dive
      duration.
AB  - When aquatically adapted mammals and birds swim submerged, they exhibit a dive
      response in which breathing ceases, heart rate slows, and blood flow to
      peripheral tissues and organs is reduced. The most intense dive response occurs
      during forced submersion which conserves blood oxygen for the brain and heart,
      thereby preventing asphyxiation. In free-diving animals, the dive response is
      less profound, and energy metabolism remains aerobic. However, even this
      relatively moderate bradycardia seems diametrically opposed to the normal
      cardiovascular response (i.e., tachycardia and peripheral vasodilation) during
      physical exertion. As a result, there has been a long-standing paradox regarding
      how aquatic mammals and birds exercise while submerged. We hypothesized based on
      cardiovascular modeling that heart rate must increase to ensure adequate oxygen
      delivery to active muscles. Here, we show that heart rate (HR) does indeed
      increase with flipper or fluke stroke frequency (SF) during voluntary, aerobic
      dives in Weddell seals (HR = 1.48SF - 8.87) and bottlenose dolphins (HR = 0.99SF
      + 2.46), respectively, two marine mammal species with different evolutionary
      lineages. These results support our hypothesis that marine mammals maintain
      aerobic muscle metabolism while swimming submerged by combining elements of both
      dive and exercise responses, with one or the other predominating depending on the
      level of exertion.

PMID- 22585424
TI  - Telomerase gene therapy: a novel approach to combat aging.

PMID- 22585423
TI  - Exosomes in Cancer Microenvironment and Beyond: have we Overlooked these
      Extracellular Messengers?
AB  - Cancer is a complex organ whose behavior is not only influenced by genetic and
      epigenetic changes in cancer cells but also by stromal cells, local extracellular
      matrix and specific tissue architecture. Intercellular communications within the
      cancer microenvironment are critical to coordinate the assembly of multiple cell
      types for an amalgamated form and function of a cancer. Exosomes are small
      membrane vesicles with an endosome origin that are released by cells into the
      extracellular environment. They carry a cargo of proteins, lipids, and nucleic
      acids and transfer their cargo to recipient cells and altering the recipient
      cells' biochemical composition, signaling pathways, and gene regulation. Exosomes
      can thus serve as extracellular messengers mediating cell-cell communication.
      Both cancer cells and stromal cells release exosomes not only into the cancer
      microenvironment but also into the circulation. In this review, we summarize the
      research done so far on cancer-derived exosomes and assess their roles as
      extracellular messengers facilitating cancer progression and metastasis.

PMID- 22585425
TI  - The antioxidant activity of allylpyrocatechol is mediated via decreased
      generation of free radicals along with escalation of antioxidant mechanisms.
AB  - Allylpyrocatechol (APC) is responsible for the antiinflammatory activity
      exhibited by the methanolic extract of leaves of Piper betle. As antiinflammatory
      compounds may display antioxidant properties and vice versa, we investigated the
      antioxidant effect of APC. APC effectively reduced phorbol-myristate-acetate
      induced generation of reactive oxygen species and superoxide in murine peritoneal
      macrophages as well as inhibited Escherichia-coli-induced phagocytic activity of
      macrophages. Furthermore, pBluescript SK(+) plasmid DNA damage induced by
      addition of sodium ascorbate was attenuated by APC as it inhibited transformation
      of the supercoiled form to a relaxed form. In addition, APC increased the
      enzymatic (catalase) and nonenzymatic (GSH) antioxidant components of murine
      macrophages. Taken together, APC exhibited an antioxidant activity which was
      mediated both via decreased generation of free radicals along with increase in
      cellular antioxidants.

PMID- 22585426
TI  - A multicenter phase II study of TSU-68, a novel oral multiple tyrosine kinase
      inhibitor, in patients with metastatic breast cancer progressing despite prior
      treatment with an anthracycline-containing regimen and taxane.
AB  - PURPOSE: TSU-68 is a novel multiple tyrosine kinase inhibitor that inhibits
      vascular endothelial growth factor receptor-2, platelet-derived growth factor
      receptor and fibroblast growth factor receptor. TSU-68 demonstrated a strong anti
      tumor effect against established human breast cancer xenografts in nude mice
      without apparent toxicity. We conducted a phase II study to evaluate the efficacy
      and safety of TSU-68 monotherapy in patients with metastatic breast cancer
      progressing despite prior treatment with an anthracycline-containing regimen and
      taxane. METHODS: TSU-68 was administered daily at a dose of 400 mg twice a day
      after meals in 20 patients. The primary endpoint was objective overall response
      rate according to the Response Evaluation Criteria in Solid Tumors guideline
      version 1.0. Secondary endpoints included clinical benefit rate (complete
      response, partial response and stable disease lasting for at least 24 weeks),
      exploratory assessments of change in mRNA levels of biological markers associated
      with angiogenesis in tumor tissue at the end of Cycle 1, and safety of TSU-68.
      RESULTS: Twenty patients were enrolled into the study from October 2002 through
      April 2003. TSU-68 monotherapy produced objective overall response in none of the
      patients; however, clinical benefit was seen in 5 % of the patients. The mRNA
      levels of CD31, Flt-1 and Flk-1/KDR showed a decreasing trend in all 4 patients
      who provided additional written informed consent for collection of tumor tissue.
      However, no significant difference was observed in the change in mRNA level due
      to the small sample size. The most common adverse drug reaction (ADR) was tumor
      pain (60 %); hematological ADRs rarely occurred, and they were mild in severity.
      Only one patient experienced grade 2 rash and no patient experienced
      hypertension. No patients experienced a grade 4 ADR and no episode of death
      related to the study treatment occurred in the 20 patients. CONCLUSIONS: TSU-68
      monotherapy produced clinical benefit in only 5 % of the patients and did not
      produce objective overall response; however, the treatment was well tolerated.
      Further evaluation of the efficacy of TSU-68 will be worthwhile because the mRNA
      levels of CD31, Flt-1 and Flk-1/KDR decreased in 4 patients.

PMID- 22585428
TI  - Novel clinical findings in a case of postnatally diagnosed trisomy 12 mosaicism.
AB  - We report on a girl with trisomy 12 mosaicism diagnosed postnatally. She has been
      followed from 4 months of age for developmental delay, unilateral sensorineural
      hearing loss, intestinal malrotation, hemi-hyperplasia, pigmentary dysplasia,
      retinopathy, and a vascular ring. To our knowledge, there have been no reports of
      complete trisomy 12 in the literature. However there have been a few reports
      describing the phenotype of individuals with trisomy 12 mosaicism. This case
      report is a description of the eighth liveborn individual diagnosed postnatally
      with this condition.

PMID- 22585427
TI  - Feasibility study of S-1 adjuvant chemotherapy in patients with colorectal
      cancer.
AB  - BACKGROUND: We evaluated the safety, efficacy, and compliance of 1-year treatment
      with S-1 in patients with stage II/III resectable colorectal cancer. METHODS: S-1
      was administered orally in two divided doses daily. The dose was assigned
      according to body surface area (BSA) as follows: BSA <1.25 m(2), 80 mg/day; BSA
      >=1.25 to <1.5 m(2), 100 mg/day; and BSA >=1.5 m(2), 120 mg/day. S-1 was given
      for 28 consecutive days, followed by a 14-day rest. The study objects were the
      rate of completion of treatment as planned at 1 year, the ratio of the actually
      administered dose to the planned dose at 1 year, and the total number of days of
      treatment. RESULTS: At 1 year, the rate of completion of treatment as planned was
      77.7 % (42/54 patients), and the ratio of the actually administered dose to the
      planned dose was 82.9 %. The mean and median total numbers of days of treatment
      were 209 and 252, respectively. Grade 3 or higher toxicity (watery eyes) occurred
      in only 1 patient. CONCLUSION: S-1 adjuvant chemotherapy had acceptable
      compliance, safety, and efficacy in patients with colorectal cancer. S-1 adjuvant
      chemotherapy is considered a possible standard treatment regimen for colorectal
      cancer.

PMID- 22585429
TI  - Expression of metastasis-associated protein 2 (MTA2) might predict proliferation
      in non-small cell lung cancer.
AB  - Metastatic tumor antigen 2 (MTA2) is a member of the MTA family that is closely
      associated with tumor progression and metastasis. In this study, the expression
      profile of MTA2 in 223 cases of non-small cell lung cancer (NSCLC) tissues and
      two lung cancer cell lines was investigated. Interestingly, we found MTA2, which
      was believed to have nuclear distribution only, was distributed in both nucleus
      and cytoplasm in normal and cancer cells. Nuclear MTA2 expression was detected in
      148 cases of NSCLC (66.4%), and was correlated with advanced TNM stages
      (p=0.023), tumor size (p=0.036), and lymph node metastasis (p=0.004). Besides,
      the Ki-67 proliferation index was significantly higher in nuclear MTA2-positive
      tumors than in nuclear MTA2-negative tumors (r=0.538, p=0.006). However, there
      was no significant difference in cytoplasmic MTA2 status by age, gender, tumor
      stage, histology, grade, lymph node metastasis, and Ki-67 proliferation index.
      Univariate analysis revealed nuclear MTA2 expression was correlated with poor
      overall survival (p=0.035), whereas there was a nonsignificant trend in the same
      direction for cytoplasmic MTA2 (p=0.134). Multivariate Cox regression analysis
      revealed the overexpression of nuclear and cytoplasmic MTA2 not to be independent
      factors predictive of poor disease outcome. Our data suggested that MTA2 might
      play roles in both the nucleus and cytoplasm in the progression of NSCLC.

PMID- 22585430
TI  - Imaging response in neuroendocrine tumors treated with targeted therapies: the
      experience of sunitinib.
AB  - Among neuroendocrine carcinomas of the gut, well-differentiated tumors are highly
      vascularized, featuring specific characteristics on contrast-enhanced imaging.
      Well-differentiated neuroendocrine tumors spontaneously harbor hypervascular
      enhancement, coexisting with areas of necrosis mainly located at the center of
      tumor lesions. When exposed to vascular endothelial growth factor (VEGFR)
      inhibitors such as sunitinib, target lesions display few if any variation in
      tumor size, but rather detectable modifications in tumor density. In several
      patients treated with targeted therapy, a significant decrease of tumor density
      at first tumor evaluation can be detected as compared to baseline. Consistently,
      the two randomized trials leading to approval of sunitinib and everolimus in
      pancreatic neuroendocrine tumors report objective response rate below 10%,
      emphasizing that Response Evaluation Criteria in Solid Tumors (RECIST), that
      focus only on the largest diameters of target lesions, may be insufficient to
      capture the full benefit of targeted therapies. Alternative criteria, such as
      those developed by Choi et al., consider both the size and the density of the
      tumor as parameters for response evaluation. Choi criteria have been recently
      proposed as a surrogate endpoint for efficacy and to identify patients that are
      good responders to VEGFR inhibitors such as sunitinib and sorafenib in advanced
      hepatocellular carcinoma, another disease highly addicted to angiogenesis.
      Preliminary data generated from patients included in the sunitinib phase III
      trial suggest that Choi criteria might also be considered as an alternative to
      RECIST to evaluate the effects of sunitinib in patients with advanced well
      differentiated neuroendocrine tumors.

PMID- 22585432
TI  - Left anterior descending artery occlusion secondary to blunt chest trauma
      diagnosed by comprehensive echocardiography and coronary angiography.
AB  - Blunt chest trauma can cause serious complications, but coronary artery occlusion
      is rare. In a 19-year-old man, 40 days after a motorcycle accident, comprehensive
      echocardiography detected left anterior descending artery occlusion and left
      ventricular dysfunction, which was confirmed by coronary angiography and
      ventriculography. Echocardiography was also able to confirm restored left
      anterior descending artery flow and improved left ventricular function after
      coronary artery bypass grafting.

PMID- 22585431
TI  - New targeted agents in gastroenteropancreatic neuroendocrine tumors.
AB  - Neuroendocrine carcinomas are rare neoplasms although of increasing incidence and
      concern. While traditionally considered of indolent nature, once they progress
      beyond surgical resectability, the outcome is ultimately fatal for the majority
      of patients. Somatostatin analogs are useful to control symptoms in functioning
      tumors and may slow tumor progression in certain disease settings, but
      sensitivity to conventional cytotoxic chemotherapy is rather limited. In this
      context, results of the recently published randomized trials with sunitinib and
      everolimus have demonstrated for the first time that there are agents able to
      positively impact on the natural history of this complex disease. In this review,
      we will discuss available data on angiogenesis and mammalian target of rapamycin
      inhibitors for the treatment of advanced well-differentiated
      gastroenteropancreatic neuroendocrine tumors.

PMID- 22585433
TI  - Quantifying the concentration of crude oil microdroplets in oil-water
      preparations.
AB  - Dissolved constituents of crude oil, particularly polycyclic aromatic
      hydrocarbons (PAHs), can contribute substantially to the toxicity of aquatic
      organisms. Measured aqueous concentrations of high-molecular weight PAHs (e.g.,
      chrysenes, benzo[a]pyrene) as well as long-chain aliphatic hydrocarbons can
      exceed the theoretical solubility of these sparingly soluble compounds. This is
      attributed to the presence of a "microdroplet" or colloidal oil phase. It is
      important to be able to quantify the dissolved fraction of these compounds in oil
      in-water preparations that are commonly used in toxicity assays because the
      interpretation of test results often assumes that the compounds are dissolved. A
      method is presented to determine the microdroplet contribution in crude oil-in
      water preparations using a comparison of predicted and measured aqueous
      concentrations. Measured concentrations are reproduced in the model by including
      both microdroplets and dissolved constituents of petroleum hydrocarbons.
      Microdroplets were found in all oil-water preparation data sets analyzed.
      Estimated microdroplet oil concentrations typically ranged from 10 to 700 ug
      oil/L water. The fraction of dissolved individual petroleum hydrocarbons ranges
      from 1.0 for highly soluble compounds (e.g., benzene, toluene, ethylbenzene, and
      xylene) to far less than 0.1 for sparingly soluble compounds (e.g., chrysenes)
      depending on the microdroplet oil concentration. The presence of these
      microdroplets complicates the interpretation of toxicity test data because they
      may exert an additional toxic effect due to a change in the exposure profile. The
      implications of the droplet model on toxicity are also discussed in terms of both
      dissolved hydrocarbons and microdroplets.

PMID- 22585434
TI  - Patterns of infant mortality from 1993 to 2007 in Belgrade (Serbia).
AB  - The population of the Republic of Serbia has been exposed to radical changes in
      living standards and employment status and inequalities in utilization of health
      care services. Given that infant mortality rates (IMR) reflect general community
      health, we evaluated the trends and mortality structure of Belgrade's infant
      population for a 15-year period (1993-2007). Data were collected from published
      and unpublished materials of the Municipal Institute of Statistics in Belgrade.
      Records were based on official notifications of live-born infants and death
      certificates. A linear regression equation was used to estimate mortality trends
      over time, while an F test was performed to assess the significance of the linear
      regression coefficient. The average IMR was 11.3 [95% confidence interval (CI)
      9.4, 13.2] per 1,000 live births for both sexes with a higher average rate
      observed for male infants. Throughout the whole period, a statistically
      significant declining trend (y = 17.072 - 0.721x, p = 0.001) was noted. The most
      common causes of death were conditions occurring during the perinatal period,
      with an average annual mortality rate of 7.7 [95% CI 6.4, 8.9] per 1,000, arising
      mainly from respiratory distress of the newborns. Regarding congenital anomalies,
      deformations of the heart and aortic and mitral valves were most frequently
      found. A statistically significant inverse correlation was observed between
      average net salary and IMR for each sex separately (for males r = -0.727, p =
      0.002, for females r = -0.721, p = 0.002) and for both sexes jointly (r = -0.759,
      p = 0.001). A decline in infant mortality in Belgrade has been observed. However,
      further promotion of health-related activities, as well as continuous
      surveillance of IMR, is required.

PMID- 22585435
TI  - Prevalence and comorbidity of nocturnal wandering in the U.S. adult general
      population.
AB  - OBJECTIVE: To assess the prevalence and comorbid conditions of nocturnal
      wandering with abnormal state of consciousness (NW) in the American general
      population. METHODS: Cross-sectional study conducted with a representative sample
      of 19,136 noninstitutionalized individuals of the U.S. general population >=18
      years old. The Sleep-EVAL expert system administered questions on life and
      sleeping habits; health; and sleep, mental, and organic disorders (DSM-IV-TR;
      International Classification of Sleep Disorders, version 2; International
      Classification of Diseases-10). RESULTS: Lifetime prevalence of NW was 29.2% (95%
      confidence interval [CI] 28.5%-29.9%). In the previous year, NW was reported by
      3.6% (3.3%-3.9%) of the sample: 1% had 2 or more episodes per month and 2.6% had
      between 1 and 12 episodes in the previous year. Family history of NW was reported
      by 30.5% of NW participants. Individuals with obstructive sleep apnea syndrome
      (odds ratio [OR] 3.9), circadian rhythm sleep disorder (OR 3.4), insomnia
      disorder (OR 2.1), alcohol abuse/dependence (OR 3.5), major depressive disorder
      (MDD) (OR 3.5), obsessive-compulsive disorder (OCD) (OR 3.9), or using over-the
      counter sleeping pills (OR 2.5) or selective serotonin reuptake inhibitor (SSRI)
      antidepressants (OR 3.0) were at higher risk of frequent NW episodes (>=2
      times/month). CONCLUSIONS: With a rate of 29.2%, lifetime prevalence of NW is
      high. SSRIs were associated with an increased risk of NW. However, these
      medications appear to precipitate events in individuals with a prior history of
      NW. Furthermore, MDD and OCD were associated with significantly greater risk of
      NW, and this was not due to the use of psychotropic medication. These psychiatric
      associations imply an increased risk due to sleep disturbance.

PMID- 22585436
TI  - Mitochondrial dynamics: general concepts and clinical implications.

PMID- 22585438
TI  - Asymptomatic subclavian-carotid double steal phenomenon due to innominate artery
      stenosis.

PMID- 22585439
TI  - Intracranial optic nerve enlargement in infantile Krabbe disease.

PMID- 22585441
TI  - Atomistic modeling of thermodynamic equilibrium and polymorphism of iron.
AB  - We develop two new modified embedded-atom method (MEAM) potentials for elemental
      iron, intended to reproduce the experimental phase stability with respect to both
      temperature and pressure. These simple interatomic potentials are fitted to a
      wide variety of material properties of bcc iron in close agreement with
      experiments. Numerous defect properties of bcc iron and bulk properties of the
      two close-packed structures calculated with these models are in reasonable
      agreement with the available first-principles calculations and experiments.
      Performance at finite temperatures of these models has also been examined using
      Monte Carlo simulations. We attempt to reproduce the experimental iron
      polymorphism at finite temperature by means of free energy computations, similar
      to the procedure previously pursued by Muller et al (2007 J. Phys.: Condens.
      Matter 19 326220), and re-examine the adequacy of the conclusion drawn in the
      study by addressing two critical aspects missing in their analysis: (i) the
      stability of the hcp structure relative to the bcc and fcc structures and (ii)
      the compatibility between the temperature and pressure dependences of the phase
      stability. Using two MEAM potentials, we are able to represent all of the
      observed structural phase transitions in iron. We discuss that the correct
      reproductions of the phase stability among three crystal structures of iron with
      respect to both temperature and pressure are incompatible with each other due to
      the lack of magnetic effects in this class of empirical interatomic potential
      models. The MEAM potentials developed in this study correctly predict, in the bcc
      structure, the self-interstitial in the (110) orientation to be the most stable
      configuration, and the screw dislocation to have a non-degenerate core structure,
      in contrast to many embedded-atom method potentials for bcc iron in the
      literature.

PMID- 22585442
TI  - The effects of the neurotoxin DSP4 on spatial learning and memory in Wistar rats.
AB  - The aim of the present study was to investigate the effect of DSP4-induced
      noradrenaline depletion on learning and memory in a spatial memory paradigm
      (holeboard). Since Harro et al. Brain Res 976:209-216 (2003) have demonstrated
      that short-term effects of DSP4 administration include both noradrenaline
      depletion and changes in dopamine and its metabolites-with the latter vanishing
      within 4 weeks after the neurotoxic lesion-the behavioural effects observed
      immediately after DSP4 administration cannot solely be related to noradrenaline.
      In the present study, spatial learning, reference memory and working memory were
      therefore assessed 5-10 weeks after DSP4 administration. Our results suggest that
      the administration of DSP4 did not lead to changes in spatial learning and memory
      when behavioural assessment was performed after a minimum of 5 weeks following
      DSP4. This lack of changes in spatial behaviour suggests that the role of
      noradrenaline regarding these functions may be limited. Future studies will
      therefore have to take into account the time-course of neurotransmitter
      alterations and behavioural changes following DSP4 administration.

PMID- 22585443
TI  - Images in endocrine pathology: thyrotoxicosis associated with destructive
      thyroiditis.

PMID- 22585444
TI  - Telephone peer support for women with gynaecological cancer: benefits and
      challenges for supporters.
AB  - OBJECTIVE: Despite the prevalence of one-to-one peer support programmes for
      people with cancer, little research has examined its impact on the supporters
      themselves. This qualitative study examined a telephone-delivered one-to-one peer
      support intervention for women with gynaecological cancer, focussing on
      supporters' subjective experiences of benefits or costs to themselves and
      challenges arising in the support process. METHODS: Semi-structured interviews (N
      = 24) were conducted with 16 women who provided peer support for 24 patients.
      Transcripts were analysed thematically using the Framework approach. RESULTS:
      Participants described significant personal benefits of providing support,
      including enhanced self-esteem and well-being, and gaining a new perspective and
      closure on their cancer experience. They experienced no adverse consequences, but
      several challenges arose, for example, finding a balance between emotional
      involvement and detachment, and supporting someone with a poor prognosis or high
      levels of negative emotion. Their accounts indicated resourcefulness in managing
      the challenges. CONCLUSIONS: Providing peer support has a valuable role to play
      in cancer survivorship; it can facilitate the final stages of moving away from
      the role of patient and help to promote a more confident post-cancer sense of
      self. However, readiness to provide support and the availability of backup from
      health-care professionals appear essential. The findings have implications for
      the selection, training and supervision of peer supporters. Future studies should
      routinely measure outcomes for peer supporters.

PMID- 22585446
TI  - Brain abnormalities in patients with Beckwith-Wiedemann syndrome.
AB  - Beckwith-Wiedemann syndrome (BWS) is an overgrowth disorder with variability in
      clinical manifestations and molecular causes. In most cases, patients with BWS
      have normal development. Cases with developmental delay are usually attributed to
      neonatal hypoglycemia or chromosome abnormalities involving copy number variation
      for genes beyond the critical BWS region at 11p15.5. Brain abnormalities have not
      previously been recognized within the BWS phenotypic spectrum. We report on seven
      cases of BWS associated with posterior fossa abnormalities. Of these, two cases
      presented with Blake's pouch cyst, two with Dandy-Walker variant (DWV; hypoplasia
      of the inferior part of the vermis), one with Dandy-Walker malformation (DWM) and
      one with a complex of DWM, dysgenesis of the corpus callosum and brain stem
      abnormality. In all these cases, molecular findings involved the centromeric
      imprinted domain on chromosome locus 11p15.5, which includes imprinting center 2
      (IC2) and the imprinted growth suppressor gene, CDKN1C. Three cases had loss of
      methylation at IC2, two had CDKN1C mutations, and one had loss of methylation at
      IC2 and a microdeletion. In one case no mutation/methylation abnormality was
      detected. These findings together with previously reported correlations suggest
      that genes in imprinted domain 2 at 11p15.5 are involved in normal midline
      development of several organs including the brain. Our data suggest that brain
      malformations may present as a finding within the BWS phenotype when the
      molecular etiology involves imprinted domain 2. Brain imaging may be useful in
      identifying such malformations in individuals with BWS and neurodevelopmental
      issues.

PMID- 22585447
TI  - IL-33 attenuates EAE by suppressing IL-17 and IFN-gamma production and inducing
      alternatively activated macrophages.
AB  - Interleukin (IL)-33, a member of the IL-1 cytokine family, is an important
      modulator of the immune system associated with several immune-mediated disorders.
      High levels of IL-33 are expressed by the central nervous system (CNS) suggesting
      a potential role of IL-33 in autoimmune CNS diseases. We have investigated the
      expression and function of IL-33 in the development of experimental autoimmune
      encephalomyelitis (EAE) in mice. We report here that IL-33 and its receptor ST2
      (IL-33Ralpha) are highly expressed in spinal cord tissue, and ST2 expression is
      markedly increased in the spinal cords of mice with EAE. Furthermore, ST2
      deficient (ST2(-/-) ) mice developed exacerbated EAE compared with wild-type (WT)
      mice while WT, but not ST2(-/-)  EAE mice treated with IL-33 developed
      significantly attenuated disease. IL-33-treated mice had reduced levels of IL-17
      and IFN-gamma but produced increased amounts of IL-5 and IL-13. Lymph node and
      splenic macrophages of IL-33-treated mice showed polarization toward an
      alternatively activated macrophage (M2) phenotype with significantly increased
      frequency of MR(+) PD-L2(+)  cells. Importantly, adoptive transfer of these IL-33
      treated macrophages attenuated EAE development. Our data therefore demonstrate
      that IL-33 plays a therapeutic role in autoimmune CNS disease by switching a
      predominantly pathogenic Th17/Th1 response to Th2 activity, and by polarization
      of anti-inflammatory M2 macrophages.

PMID- 22585449
TI  - Introduction--Knowledge translation and urban health equity: advancing the
      agenda.
AB  - In 2011, an interdisciplinary symposium was organized in Toronto, Canada to
      investigate prevailing models of health policy change in the knowledge
      translation literature and to assess the applicability of these models for equity
      focused urban health research. The papers resulting from the symposium have been
      published together, in the Journal of Urban Health, along with this introductory
      essay. This essay describes how the different papers grapple in different ways
      with how to understand and to bridge the gaps between urban health research and
      action. The breadth of perspectives reflected in the papers (e.g., social
      epidemiology, public health, political science, sociology, critical labor
      studies, and educational psychology) shed much light on core tensions in the
      relationship between KT and health equity. The first tension is whether the
      content of evidence or the context of decision making is the strong determinate
      of research impact in relation to health equity policy. The second tension is
      whether relationships between health equity researchers and decision makers are
      best viewed in terms of collaboration or of conflict. The third concerns the role
      that power plays in evidence-based policy making, when the issues at stake are
      not only empirical but also normative.

PMID- 22585448
TI  - Spatial access to sterile syringes and the odds of injecting with an unsterile
      syringe among injectors: a longitudinal multilevel study.
AB  - Despite the 2010 repeal of the ban on spending federal monies to fund syringe
      exchange programs (SEPs) in the U.S.A., these interventions--and specifically SEP
      site locations--remain controversial. To further inform discussions about the
      location of SEP sites, this longitudinal multilevel study investigates the
      relationship between spatial access to sterile syringes distributed by SEPs in
      New York City (NYC) United Hospital Fund (UHF) districts and injecting with an
      unsterile syringe among injectors over time (1995-2006). Annual measures of
      spatial access to syringes in each UHF district (N = 42) were created using data
      on SEP site locations and site-specific syringe distribution data. Individual
      level data on unsterile injecting among injectors (N = 4,067) living in these
      districts, and on individual-level covariates, were drawn from the Risk Factors
      study, an ongoing cross-sectional study of NYC drug users. We used multilevel
      models to explore the relationship of district-level access to syringes to the
      odds of injecting with an unsterile syringe in >75% of injection events in the
      past 6 months, and to test whether this relationship varied by district-level
      arrest rates (per 1,000 residents) for drug and drug paraphernalia possession.
      The relationship between district-level access to syringes and the odds of
      injecting with an unsterile syringe depended on district-level arrest rates. In
      districts with low baseline arrest rates, better syringe access was associated
      with a decline in the odds of frequently injecting with an unsterile syringe
      (AOR, 0.95). In districts with no baseline syringe access, higher arrest rates
      were associated with increased odds of frequently injecting with an unsterile
      syringe (AOR, 1.02) When both interventions were present, arrest rates eroded the
      protective effects of spatial access to syringes. Spatial access to syringes in
      small geographic areas appears to reduce the odds of injecting with an unsterile
      syringe among local injectors, and arrest rates elevate these odds. Policies and
      practices that curtail syringe flow in geographic areas (e.g., restrictions on
      SEP locations or syringe distribution) or that make it difficult for injectors to
      use the sterile syringes they have acquired may damage local injectors' efforts
      to reduce HIV transmission and other injection-related harms.

PMID- 22585450
TI  - Effects of Crataegus microphylla on vascular dysfunction in streptozotocin
      induced diabetic rats.
AB  - Vascular dysfunction plays a key role in the pathogenesis of diabetic vascular
      disease. In this study, we aimed to investigate whether chronic in vivo treatment
      of Crataegus microphylla (CM) extract in diabetic rats induced with
      streptozotocin (STZ, intraperitoneal, 65 mg/kg) preserves vascular function and
      to evaluate whether the reduction of inducible nitric oxide synthase (iNOS),
      proinflammatory cytokines, and lipid peroxidation mediates its mechanisms of
      action. Starting at 4 weeks of diabetes, CM extract (100 mg/kg) was administrated
      to diabetic rats for 4 weeks. In aortic rings, relaxation to acetylcholine and
      vasoreactivity to noradrenaline were impaired, whereas aortic iNOS expression and
      plasma tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), total
      nitrite-nitrate, and malondialdehite levels were increased in diabetic rats
      compared with controls. Chronic CM treatment significantly corrected all the
      above abnormalities in diabetic rats. In comparison, pretreatment of the aorta of
      diabetic rats with N-[3(aminomethyl) benzyl]-acetamidine, dihydrochloride (10(-5)
      M), a selective inhibitor of iNOS, produced a similar recovery in vascular
      reactivity. These results suggest that chronic in vivo treatment of CM preserves
      endothelium-dependent relaxation and vascular contraction in STZ-induced
      diabetes, possibly by reducing iNOS expression in the aorta and by decreasing
      plasma levels of TNF-alpha and IL-6 and by preventing lipid peroxidation.

PMID- 22585451
TI  - CD45/CD11b positive subsets of adult lung anchorage-independent cells harness
      epithelial stem cells in culture.
AB  - Compensatory growth is mediated by multiple cell types that interact during organ
      repair. To elucidate the relationship between stem/progenitor cells that
      proliferate or differentiate and somatic cells of the lung, we used a novel
      organotypic ex vivo pneumoexplant system. Applying this technique, we identified
      a sustained culture of repopulating adult progenitors in the form of free
      floating anchorage-independent cells (AICs). AICs did not express integrin
      proteins alpha5, beta3 and beta7, and constituted 37% of the total culture at day
      14, yielding a mixed yet conservative population that recapitulated RNA
      expression patterns of the healthy lung. AICs exhibited rapid proliferation
      manifested by a marked 60-fold increase in cell numbers by day 21. More than 50%
      of the AIC population was c-KIT(+) or double-positive for CD45(+) and CD11b(+)
      antigenic determinants, consistent with cells of hematopoietic origin. The latter
      subset was found to be enriched with prosurfactant protein-C and SCGB1A1
      expressing putative stem cells and with aquaporin-5 producing cells,
      characteristic of terminally differentiated alveolar epithelial type-1
      pneumocytes. At the air/gel interface, AICs undergo remodeling to form a cellular
      lining, whereas TGF(beta)1 treatment modifies protein expression properties to
      further imply a robust effect of the microenvironment on AIC phenotypic changes.
      These data confirm the active participation of clonogenic hematopoietic stem
      cells in a mammalian model of lung repair and validate mixed stem/somatic cell
      cultures, which license sustained cell viability, proliferation and
      differentiation, for use in studies of compensatory pulmonary growth.

PMID- 22585452
TI  - Endoscopic endonasal resection of the odontoid peg--case report and literature
      review.

PMID- 22585453
TI  - Giovanni Battista Morgagni (1682-1771): his anatomic majesty's contributions to
      the neurosciences.
AB  - INTRODUCTION: Giovanni Battista Morgagni is considered the Father of Pathology
      and contributed much to our early understanding of neuropathology. For example,
      he introduced the concept that diagnosis, prognosis, and treatment of disease
      must be based on an exact understanding of the pathologic changes in anatomic
      structures. Additionally, he contributed to what would become the discipline of
      neurosurgery and, for example, performed trepanation for head trauma.
      CONCLUSIONS: It is the contributions of such early pioneers as Morgagni that our
      current understanding of the neurosciences is based.

PMID- 22585455
TI  - The pleuro-esophageal muscle: a disregarded anatomical structure.
AB  - A transverse muscular band extending from the left pleura to the esophagus was
      detected during routine dissection of posterior mediastinum in Anatomy Department
      of Ege University Medical Faculty. As a result of a detailed review of the
      literature, we found that this structure is named as the pleuro-esophageal
      muscle. This muscle was made of smooth fibers, acting as an anchoring structure
      to the lower part of the esophagus. While the entire esophageal muscle is smooth
      in the early stage of fetal development, this muscle probably derives as an early
      separation from the esophagus.

PMID- 22585454
TI  - Serial interferon-gamma release assays after chemoprophylaxis in a tuberculosis
      outbreak cohort.
AB  - PURPOSE: Interferon-gamma release assay (IGRA) results have been suggested as a
      surrogate marker of treatment response in latent tuberculosis infection (LTBI).
      However, data have not been consistent, and most previous studies focused on
      participants taking isoniazid prophylaxis. The aim of this study was to elucidate
      the changes in the IGRA results in patients who underwent chemoprophylaxis with
      isoniazid and rifampicin daily for 3 months. METHODS: In a TB outbreak cohort, 26
      asymptomatic close contacts with normal chest radiographs and positive
      QuantiFERON-TB Gold In-Tube assay (QFT-GIT) results were recruited. These
      patients were treated with isoniazid and rifampicin daily for 3 months. The QFT
      GIT was repeated at 3 and 6 months following treatment initiation. RESULTS:
      Compared with the initial QFT-GIT results (3.59 +/- 3.39 IU/mL), the interferon
      gamma (IFN-gamma) levels had decreased significantly at 6 months (0.84 +/- 1.14
      IU/mL; P = 0.005), but not at 3 months (3.58 +/- 3.64 IU/mL; P = 0.98).
      Reversions occurred in seven (26.9 %) patients at 3 months and in an additional
      two participants at 6 months; a total of nine participants (34.6 %) had
      reversions. Recent conversion was associated with reversion of the test results
      (odds ratio 26.3, 95 % confidence interval 3.04-226.6). CONCLUSION:
      Chemoprophylaxis with isoniazid and rifampicin generally decreased IFN-gamma
      levels among tuberculosis contacts. However, only a small portion of participants
      achieved reversion.

PMID- 22585456
TI  - Adult leptomeningeal cerebellar heterotopia in contact with the posterior
      inferior cerebellar artery.
AB  - A leptomeningeal mass was encountered during microdissection of a 63-year-old
      male cadaver, located dorsal to the left side of the medulla oblongata. The
      structure was compressing the posterior inferior cerebellar artery (PICA) and was
      composed of cerebellar-like tissue. Immunohistochemistry for S100 protein, glial
      fibrillary acidic protein and neurofilaments (NF, the triplet proteins and the
      200 kD antibody) on paraffin-embedded samples confirmed the cerebellar
      heterotopion. Abundant Lewy-like degenerative bodies were also identified within
      the heterotopion; they were positive for the NF triplet and negative for the 200
      kD neurofilaments. Purkinje cells were rare. This is the first evidence of a
      leptomeningeal cerebellar heterotopia in contact with PICA in adult. Such
      subtentorial heterotopias, even if rare, should be searched for during clinical,
      paraclinical and surgical explorations of the posterior fossa.

PMID- 22585457
TI  - Superconductivity at 5.2 K in ZrTe3 polycrystals and the effect of Cu and Ag
      intercalation.
AB  - We report the occurrence of superconductivity in polycrystalline samples of
      ZrTe(3) at temperature 5.2 K at ambient pressure. The superconducting state
      coexists with the charge density wave (CDW) phase, which sets in at 63 K. The
      intercalation of Cu or Ag does not have any bearing on the superconducting
      transition temperature but suppresses the CDW state. The feature of a CDW anomaly
      in these compounds is clearly seen in the DC magnetization data. Resistivity data
      are analyzed in order to estimate the relative loss of carriers and reduction in
      the nested Fermi surface area upon CDW formation in ZrTe(3) and the intercalated
      compounds.

PMID- 22585458
TI  - Wischnewski spots and hypothermia: sensitive, specific, or serendipitous?

PMID- 22585459
TI  - First trimester transabdominal chorionic villus sampling--does the needle matter?
AB  - PURPOSE: To compare first-trimester transabdominal chorionic villus samples (TA
      CVS) when obtained by 20-gauge amniocentesis versus lancet needles. METHODS: This
      is a retrospective study of all women with viable singleton pregnancies
      undergoing TA-CVS from 01/01/2009 to 03/31/2011. All CVS were performed by a
      single operator using a freehand technique and amniocentesis needles from
      01/01/2009 to 08/31/2010 and lancet needles from 09/01/2010 to 03/31/2011. All
      samples were processed by the same laboratory. RESULTS: There were no differences
      between groups regarding maternal age, weight, gestational age at CVS, indication
      for CVS, uterine position, or placental location. Lancet needles were associated
      with significantly larger samples (median 18 [range 3-40] versus 7 [range 1-33]
      mg, p < 0.0001), more successful in situ hybridization (96% versus 74.2%, p =
      0.03), and faster result reporting (median 7 [range 5-12] versus 9 [range 6-26]
      days, p = 0.002). CONCLUSIONS: Needle type may be clinically important when
      selecting 20-gauge TA-CVS needles.

PMID- 22585460
TI  - Risk of cancer in relatives of children born with isolated cleft lip and palate.

PMID- 22585461
TI  - Surgical bedside master console for neurosurgical robotic system.
AB  - PURPOSE: We are currently developing a neurosurgical robotic system that
      facilitates access to residual tumors and improves brain tumor removal surgical
      outcomes. The system combines conventional and robotic surgery allowing for a
      quick conversion between the procedures. This concept requires a new master
      console that can be positioned at the surgical bedside and be sterilized.
      METHODS: The master console was developed using new technologies, such as a
      parallel mechanism and pneumatic sensors. The parallel mechanism is a purely
      passive 5-DOF (degrees of freedom) joystick based on the author's haptic
      research. The parallel mechanism enables motion input of conventional brain tumor
      removal surgery with a compact, intuitive interface that can be used in a
      conventional surgical environment. In addition, the pneumatic sensors implemented
      on the mechanism provide an intuitive interface and electrically isolate the tool
      parts from the mechanism so they can be easily sterilized. RESULTS: The 5-DOF
      parallel mechanism is compact (17 cm width, 19cm depth, and 15cm height),
      provides a 505,050 mm and 90 degrees  workspace and is highly backdrivable (0.27N
      of resistance force representing the surgical motion). The evaluation tests
      revealed that the pneumatic sensors can properly measure the suction strength,
      grasping force, and hand contact. In addition, an installability test showed that
      the master console can be used in a conventional surgical environment.
      CONCLUSION: The proposed master console design was shown to be feasible for
      operative neurosurgery based on comprehensive testing. This master console is
      currently being tested for master-slave control with a surgical robotic system.

PMID- 22585462
TI  - Markerless estimation of patient orientation, posture and pose using range and
      pressure imaging : for automatic patient setup and scanner initialization in
      tomographic imaging.
AB  - PURPOSE: In diagnostic tomographic imaging, patient setup and scanner
      initialization is a manual, tedious procedure in clinical practice. A fully
      automatic detection of the patient's position, orientation, posture and pose on
      the patient table holds great potential for optimizing this part of the imaging
      workflow. We propose a markerless framework that is capable of extracting this
      information within seconds from either range imaging (RI) or pressure imaging
      (PI) data. METHODS: The proposed method is composed of three stages: First, the
      position and orientation of the reclined patient are determined. Second, the
      patient's posture is classified. Third, based on the estimated orientation and
      posture, an approximate body pose is recovered by fitting an articulated model to
      the observed RI/PI data. Being a key issue for clinical application, our approach
      does not require an initialization pose. RESULTS: In a case study on real data
      from 16 subjects, the performance of the proposed system was evaluated
      quantitatively with a 3-D time-of-flight RI camera and a pressure sensing
      mattress (PI). The patient orientation was successfully determined for all
      subjects, independent of the modality. At the posture recognition stage, our
      method achieved mean classification rates of 79.4% for RI and 95.5% for PI data,
      respectively. Concerning the approximate body pose estimation, anatomical body
      landmarks were localized with an accuracy of +/-5.84 cm (RI) and +/-5.53 cm (PI).
      CONCLUSIONS: The results indicate that an estimation of the patient's position,
      orientation, posture and pose using RI and PI sensors, respectively, is feasible,
      and beneficial for optimizing the workflow in diagnostic tomographic imaging.
      Both modalities achieved comparable pose estimation results using different
      models that account for modality-specific characteristics. PI outperforms RI in
      discriminating between prone and supine postures due to the distinctive pressure
      distribution of the human body.

PMID- 22585463
TI  - An electromagnetic "Tracker-in-Table" configuration for X-ray fluoroscopy and
      cone-beam CT-guided surgery.
AB  - PURPOSE: A novel electromagnetic tracking configuration was characterized and
      implemented for image-guided surgery incorporating C-arm fluoroscopy and/or cone
      beam CT (CBCT). The tracker employed a field generator (FG) with an open
      rectangular aperture and a frame enclosure with two essentially hollow sides,
      yielding a design that presents little or no X-ray attenuation across the C-arm
      orbit. The "Window" FG (WFG) was characterized in comparison with a conventional
      "Aurora" FG (AFG), and a configuration in which the WFG was incorporated directly
      into the operating table was investigated in preclinical phantom studies. METHOD:
      The geometric accuracy and field of view (FOV) of the WFG and AFG were evaluated
      in terms of target registration error (TRE) using an acrylic phantom on an
      (electromagnetic compatible) experimental bench. The WFG design was incorporated
      in a prototype operating table featuring a carbon fiber top beneath, which the FG
      could be translated for positioning under the patient. The X-ray compatibility
      was evaluated using a prototype mobile C-arm for fluoroscopy and CBCT in an
      anthropomorphic chest phantom. The susceptibility to EM field distortion
      associated with surgical tools (e.g., spine screws) and the C-arm itself was
      investigated in terms of TRE, and calibration methods were tested to provide
      robust image-world registration with minimal perturbation from the rotational C
      arm. RESULTS: The WFG demonstrated mean TRE of 1.28 +/- 0.79 mm compared to 1.13
      +/- 0.72 mm for the AFG, with no statistically significant difference between the
      two (p = 0.32 and n = 250). The WFG exhibited a deeper field of view by ~10 cm
      providing an equivalent degree of geometric accuracy to a depth of z ~55 cm,
      compared to z ~45 cm for the AFG. Although the presence of a small number of
      spine screws did not degrade tracker accuracy, the mobile C-arm perturbed the
      electromagnetic field sufficiently to degrade TRE; however, a calibration method
      was identified to mitigate the effect. Specifically, the average calibration
      between posterior-anterior and lateral orientations of the C-arm was found to
      yield fairly robust registration for any C-arm pose with only a slight reduction
      in geometric accuracy (1.43 +/- 0.31 mm in comparison with 1.28 +/- 0.79 mm, p =
      0.05). The WFG demonstrated reasonable X-ray compatibility, although the initial
      design of the window frame included suboptimal material and shape of the side
      bars that caused a level of streak artifacts in CBCT reconstructions. The streak
      artifacts were of sufficient magnitude to degrade soft-tissue visibility in CBCT
      but were negligible in the context of high-contrast imaging tasks (e.g., bone
      visualization). CONCLUSION: The open frame of the WFG offers a potentially
      valuable configuration for electromagnetic trackers in image-guided surgery
      applications that are based on X-ray fluoroscopy and/or CBCT. The geometric
      accuracy and FOV are comparable to the conventional AFG and offers increased
      depth (z-direction) FOV. Incorporation directly within the operating table offers
      a streamlined implementation in which the tracker is in place but "invisible,"
      potentially simplifying tableside logistics, avoidance of the sterile field, and
      compatibility with X-ray imaging.

PMID- 22585464
TI  - Retinoic acid alleviates Con A-induced hepatitis and differentially regulates
      effector production in NKT cells.
AB  - Retinoic acid (RA) is a diverse regulator of immune responses. Although RA
      promotes natural killer T (NKT) cell activation in vitro by increasing CD1d
      expression on antigen-presenting cells (APCs), the direct effects of RA on NKT
      cell responses in vivo are not known. In the present study, we demonstrated the
      effect of RA on the severity of Con A-induced hepatitis and molecular changes of
      NKT cells. First, we demonstrated that Con A-induced liver damage was ameliorated
      by RA. In correlation with cytokine levels in serum, RA regulated the production
      of IFN-gamma and IL-4 but not TNF-alpha by NKT cells without influencing the NKT
      cell activation status. However, RA did not alleviate alpha-GalCer-induced liver
      injury, even though it reduced IFN-gamma and IL-4 but not TNF-alpha levels in
      serum. This regulation was also detected when liver mononuclear cells (MNCs) or
      NKT hybridoma cells were treated with RA in vitro. The regulatory effect of RA on
      NKT cells was mediated by RAR-alpha, and RA reduced the phosphorylation of MAPK.
      These results suggest that RA differentially modulates the production of effector
      cytokines by NKT cells in hepatitis, and the suppressive effect of RA on
      hepatitis varies with the pathogenic mechanism of liver injury.

PMID- 22585466
TI  - A novel way to isolate MSCs from umbilical cords.

PMID- 22585465
TI  - Cognitive features 10 or more years after successful breast cancer survival:
      comparisons across types of cancer interventions.
AB  - BACKGROUND: The present study examined the long-term cognitive implications of
      cancer treatment among breast cancer survivors aged 65 years and older to better
      understand the long term implications of cancer treatment. METHODS: Fifty-seven
      women survivors were compared with 30 healthy older female adult comparisons,
      matched in terms of age and education, with no history of cancer. Cancer
      survivors were also compared on the basis of treatment intervention, involving
      chemotherapy (n = 27) versus local therapy through surgery and radiation (n =
      30). RESULTS: As a group, the breast cancer survivors scored lower on measures of
      general cognitive function, working memory, psychomotor speed, and executive
      function when compared with the normal comparisons. Among the cancer survivors,
      those who received local therapy scored lower than the other survivors and normal
      comparisons on measures of verbal learning, visual perception and construction,
      as well as visual attention and short-term retention. CONCLUSIONS: Our findings
      suggest that cognitive outcomes may involve greater age-related deficits among
      older cancer survivors compared with matched healthy subjects.

PMID- 22585467
TI  - Critical evaluation and further development of methods for testing ecotoxicity at
      multiple pH using Daphnia magna and Pseudokirchneriella subcapitata.
AB  - To meet the requirements of risk assessment legislature regarding the ecotoxicity
      of ionizing compounds, the present study attempts to establish easy, robust
      methods for testing ecotoxicity at various pH levels. An overview is given of the
      buffering methods found in the literature. This is supplemented by a series of
      experiments where toxicity and ability to stabilize pH of seven common buffering
      compounds was tested on Daphnia magna and Pseudokirchneriella subcapitata. We
      consider a buffer applicable at a given concentration if the pH drift is below
      0.2 pH units, and if there are no toxic effects. Twenty-four- and 48-h acute
      toxicity tests with D. magna were carried on a series of organic buffers with pH
      monitoring. Based on the experimental results it is possible to give
      recommendations for buffer concentrations for use in toxicity testing with D.
      magna at pH levels in the range of pH 6.0-7.8 for 48 h exposure, and pH 6.0-9.5
      for 24 h exposure. Forty-eight- and 72-h growth inhibition tests with P.
      subcapitata were carried out, and recommendations for buffer concentrations at pH
      7.5 and 8.0 are made for both 48 and 72 h of exposure.

PMID- 22585468
TI  - Extrinsic electronic transport in La0.7(Sr,Ca)0.3MnO3 films deposited on step
      edges and bicrystal substrates.
AB  - In this paper, the electronic transport of La(0.7)(Sr,Ca)(0.3)MnO(3) films grown
      by pulsed laser deposition on a LaAlO(3)(001) substrate with deep parallel
      structured steps and a 30 degrees  symmetric bicrystal SrTiO(3)(001) substrate
      have been discussed. The electronic transport properties have been related to the
      well-known extrinsic transport of bulk manganite compounds. The spin-glass-like
      behavior with a characteristic peak at 20 K and domain formation at the grain
      boundary is observed. Further, it has been quantified from the resonant tunneling
      model that mixed magnetic interactions play a significant role in the manganite
      films deposited on step edges.

PMID- 22585469
TI  - Effectiveness and safety of the Levitan FPS ScopeTM for tracheal intubation under
      general anesthesia with a simulated difficult airway.
AB  - PURPOSE: Studies show that the Levitan FPS (first pass success) ScopeTM (LFS) is
      analogous to a bougie in simulated difficult airways with comparable tracheal
      intubation success rates. In this study, the efficacy and safety of tracheal
      intubation with the LFS was compared with that of the Macintosh laryngoscope
      utilizing manual in-line stabilization (MILS) to simulate difficult airways.
      METHODS: Ninety-four subjects successfully completed the trial. Manual in-line
      stabilization of the cervical spine was applied and the initial laryngoscopy was
      performed using either the Macintosh or the LFS in conjunction with the
      Macintosh. Following the initial grading, a second laryngoscopy was repeated
      using the second randomized technique. Cormack-Lehane grades, percentage of
      glottic opening (POGO) scores, time to intubate, number of intubation attempts,
      and the use of alternate techniques were recorded. The anesthesiologist rated the
      subjective difficulty in using each technique with a numeric rating scale and a
      visual rating scale. RESULTS: There was no significant difference in the primary
      outcome "good laryngoscopic views" (Cormack-Lehane grade 1 and 2) compared with
      "poor laryngoscopic views" (Cormack-Lehane grade 3 and 4) between the LFS and the
      Macintosh. There were higher POGO scores with the LFS compared with the Macintosh
      (80% vs 20%, respectively; P < 0.0001), but this did not translate to easier
      intubations, as documented by the need for an alternate intubation technique or
      time to intubate (< 30 and < 60 sec, respectively). The incidence of mucosal
      trauma, sore throat, and hemodynamic responses did not differ significantly
      between the two techniques. CONCLUSION: The LFS in conjunction with the Macintosh
      laryngoscope does not improve the efficacy or safety of tracheal intubation in a
      simulated difficult airway.

PMID- 22585470
TI  - Sugammadex for treatment of postoperative residual curarization in a morbidly
      obese patient.

PMID- 22585471
TI  - Management of Esophageal Squamous Cell Carcinoma with Definitive
      Chemoradiotherapy in a Patient with Scleroderma: Case Report and Review of the
      Literature.

PMID- 22585472
TI  - How it all began: a personal history of gel electrophoresis.
AB  - Arne Tiselius' moving boundary electrophoresis method was still in general use in
      1951 when this personal history begins, although zonal electrophoresis with a
      variety of supporting media (e.g., filter paper or starch grains) was beginning
      to replace it. This chapter is an account of 10 years of experiments carried out
      by the author during which molecular sieving gel electrophoresis was developed
      and common genetic variants of two proteins, haptoglobin and transferrin, were
      discovered in normal individuals. Most of the figures are images of pages from
      the author's laboratory notebooks, which are still available, so that some of the
      excitement of the time and the humorous moments are perhaps apparent. Alkaline
      gels, acidic gels with and without denaturants, vertical gels, two-dimensional
      gels, and gels with differences in starch concentration are presented. The subtle
      details that can be discerned in these various gels played an indispensable role
      in determining the nature of the change in the haptoglobin gene (Hp) that leads
      to the polymeric series characteristic of Hp ( 2 ) /Hp ( 2 ) homozygotes. Where
      possible, the names of scientific friends who made this saga of gel
      electrophoresis so memorable and enjoyable are gratefully included.

PMID- 22585473
TI  - Introduction to protein electrophoresis.
AB  - This chapter discusses, briefly, the developments in electrophoresis of proteins
      from Tiselius' moving boundary electrophoresis to the modern day two-dimensional
      polyacrylamide gel electrophoresis. It also touches upon the staining methods
      used to visualize total proteins postelectrophoresis.

PMID- 22585474
TI  - Protein quantification methods to determine protein concentration prior to
      electrophoresis.
AB  - During each step of a protein isolation technique, if enzyme activity is to be
      determined and before a protein mixture is separated on a polyacrylamide
      electrophoresis gel, it is important to determine the concentration of the
      protein(s) in solution. Measuring protein concentration involves absorbance in
      the UV range or staining the protein with dyes or copper. This review describes
      the various protein determination methods that can be employed to measure protein
      concentration in solution.

PMID- 22585475
TI  - Protein solubilization: attend to the choice of lysis buffer.
AB  - The efficient extraction of proteins of interest from cells and tissues is not
      always straightforward. In this process, the use of the optimal lysis buffer for
      protein solubilization should be considered. Here we demonstrate the use of a
      urea/thiourea lysis buffer, based on O'Farrell's buffer, and compare its
      effectiveness for solubilization of proteins from smooth muscle with the often
      utilized RIPA lysis buffer.

PMID- 22585476
TI  - Native polyacrylamide gels.
AB  - Usually proteins are separated by polyacrylamide gel electrophoresis (PAGE) in
      the presence of a detergent and under (heat-) denaturing and (non- or) reducing
      conditions. The most commonly used detergent is sodium dodecyl sulfate (SDS). The
      major function of SDS is to shield the respective charge of the proteins present
      in the mixture to be analyzed and to provide all proteins with a negative charge.
      As a consequence, the proteins will be separated according to their molecular
      weight. Electrophoresis of proteins can also be performed in the absence of SDS.
      Using such "native" conditions, the charge of each of the proteins, which will
      depend on the primary amino acid sequence of the protein (isoelectric point) and
      the pH during electrophoresis, will mainly influence the mobility of the
      respective protein during electrophoresis. Here we describe a starting protocol
      for "native" PAGE.

PMID- 22585477
TI  - Cationic electrophoresis.
AB  - Denaturing, discontinuous electrophoresis in the presence of SDS has become a
      standard method for the protein scientist. However, there are situations where
      this method produces suboptimal results. In these cases, electrophoresis in the
      presence of positively charged detergents such as cetyltrimethylammonium bromide
      (CTAB) may work considerably better. Methods for electrophoresis and staining of
      such gels are presented.

PMID- 22585478
TI  - SARCOSYL-PAGE: a new electrophoretic method for the separation and immunological
      detection of PEGylated proteins.
AB  - PEGylation of recombinant proteins and synthetic peptides aims to generate
      biopharmaceuticals with altered physical properties. The modification may lead to
      a prolonged serum half-life caused by a decreased receptor-mediated endocytosis
      and/or a delay in renal clearance caused by the increased hydrodynamic volume of
      the pharmaceutical. MIRCERA, a PEGylated recombinant erythropoietin (rhEpo)
      frequently used in the treatment of anemia due to chronic kidney disease, has
      been also abused by athletes as a performance-enhancing drug. While it can be
      detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)
      and immunoblotting, the sensitivity of the test is significantly lower compared
      to other epoetins. By replacing SDS with sarcosyl in the sample and running
      buffers, the interaction between SDS and the PEG group of the protein no longer
      reduces the affinity of the monoclonal anti-Epo antibody (clone AE7A5) to the
      protein chain. Contrary to SDS, sarcosyl only binds to the amino acid chain of
      the PEGylated protein, thus leading to enhanced antibody binding and a sharper
      electrophoretic band. While the method was originally developed for anti-doping
      purposes, it may be also useful for other PEGylated proteins and their
      electrophoretic separation and immunological detection.

PMID- 22585479
TI  - Tricine-SDS-PAGE.
AB  - Tricine-sodium dodecyl sulphate-polyacrylamide gel electrophoresis (tricine-SDS
      PAGE) is an efficient way of separating low-molecular-mass proteins. However, the
      standard system is quite complicated and specifically may not be useful when the
      separated proteins require to be recovered from the gel for quantitative
      analysis. Here, we describe a simplified system whereby these smaller proteins
      can be resolved in comparatively low-percentage gels which have high
      compatibility with modern detectors such as UV and inductively coupled plasma
      mass spectrometry (ICP-MS).

PMID- 22585480
TI  - Analysis of protein glycation using phenylboronate acrylamide gel
      electrophoresis.
AB  - Carbohydrate modification of proteins adds complexity and diversity to the
      proteome. However, undesired carbohydrate modifications also occur in the form of
      glycation, resulting in diseases such as diabetes, Alzheimer's disease,
      autoimmune diseases, and cancer. The analysis of glycated proteins is challenging
      due to their complexity and variability. Numerous analytical techniques have been
      developed that require expensive specialised equipment and complex data analysis.
      In this chapter, we describe a simple electrophoresis-based method that enables
      users to detect, identify, and analyze these post-translational modifications.
      This new cost-effective methodology will aid the detection of unwanted glycation
      products in processed foods and may lead to new diagnostics and therapeutics for
      age-related chronic diseases and glycosylation disorders.

PMID- 22585481
TI  - Protein electrophoresis in agarose gels for separating high molecular weight
      proteins.
AB  - Very large proteins (subunit sizes >200 kDa) are difficult to electrophoretically
      separate on polyacrylamide gels. A SDS vertical agarose gel system has been
      developed that has vastly improved resolving power for very large proteins.
      Proteins with molecular masses between 200 and 4,000 kDa can be clearly
      separated. Inclusion of a reducing agent in the upper reservoir buffer has been
      found to be a key technical procedure for obtaining optimum resolution.

PMID- 22585482
TI  - Increase in local protein concentration by field-inversion gel electrophoresis.
AB  - Proteins that migrate through cross-linked polyacrylamide gels (PAGs) under the
      influence of a constant electric field experience negative factors, such as
      diffusion and nonspecific trapping in the gel matrix. These negative factors
      reduce protein concentrations within a defined gel volume with increasing
      migration distance and, therefore, decrease protein recovery efficiency. Here, we
      describe the enhancement of protein separation efficiency up to twofold in
      conventional one-dimensional PAG electrophoresis (1D PAGE), two-dimensional (2D)
      PAGE, and native PAGE by implementing pulses of inverted electric field during
      gel electrophoresis.

PMID- 22585483
TI  - A combined free flow electrophoresis and DIGE approach to compare proteins in
      complex biological samples.
AB  - Free flow electrophoresis (FFE) has been applied in numerous studies as a protein
      separation technique due to its multiple advantages such as fast and efficient
      sample recovery, high resolving power, high reproducibility, and wide
      applicability to protein classes. As a stand-alone platform however, its utility
      in comparative proteomic analysis is limited as protein samples must be run
      sequentially rather than simultaneously which introduces inherent variability
      when attempting to perform quantitative analysis. Here we describe an approach
      combining fluorescent CyDye technology (DIGE) with FFE to simultaneously separate
      and identify differentially expressed proteins in a model cell system.

PMID- 22585484
TI  - Immunofixation electrophoresis for identification of proteins and specific
      antibodies.
AB  - Immunofixation electrophoresis (IFE) is a technique for the identification of
      proteins within complex mixtures after separation by either conventional zone
      electrophoresis or isoelectric focusing. Most commonly antigens (which are often
      immunoglobulins) are separated by electrophoresis followed by precipitation with
      specific antibodies in situ. However, immunoglobulins with specific reactivity
      can be also precipitated with the proper antigens after electrophoresis in
      reverse or reversed IFE. Because of its great versatility, potentially high
      sensitivity, ease to perform and customize, and relatively low cost with no
      requirement for expensive instrumentation, manual IFE remains a valuable tool for
      both clinical diagnostic testing and research. Any low-viscosity body fluid
      specimen or, possibly, culture fluid could be tested with IFE if proper
      antibodies (or antigens in reverse[d] IFE) are available. After pretreatment with
      chaotropic and/or reducing agents, even high-viscosity specimens might be
      amenable to testing with IFE.

PMID- 22585485
TI  - Microchip electrophoresis, with respect to "profiling of Abeta peptides in the
      cerebrospinal fluid of patients with Alzheimer's disease".
AB  - Aggregation of beta amyloid peptides especially Abeta1-42 in amyloid plaques is
      one of the major -neuropathological events in Alzheimer's disease. This event is
      normally accompanied by a relative reduction of the concentration of Abeta1-42 in
      the cerebrospinal fluid (CSF) of patients developing the signs of Alzheimer's
      disease. Here, we describe a microchip gel electrophoresis method in a
      polydimethylsiloxane (PDMS) chip that enables rapid profiling of major Abeta
      peptides. The method was applied to compare the relative concentration of Abeta1
      42 with other Abeta peptides, for example, Abeta 1-40 in CSF. In order to
      increase the sensitivity of detection, Abeta peptides in the CSF samples were
      first captured and concentrated using magnetic beads coated with specific anti
      Abeta antibodies.

PMID- 22585486
TI  - A Foodomics approach: CE-MS for comparative metabolomics of colon cancer cells
      treated with dietary polyphenols.
AB  - The potential of capillary electrophoresis-mass spectrometry (CE-MS) for
      metabolomics is demonstrated through the analysis of metabolites from human HT29
      colon cancer cells treated and non-treated with dietary polyphenols. Prior to CE
      MS analysis, four different metabolite purification strategies are investigated.
      Namely, the results obtained after methanol deproteinization, ultrafiltration,
      and two solid-phase extraction methods using C18 and polymer-based cartridges are
      described. These generic methods can have broad applications to analyze
      metabolites in a large variety of matrices and fields, including the new
      Foodomics area.

PMID- 22585487
TI  - Peptide fractionation by SDS-free polyacrylamide gel electrophoresis for
      proteomic analysis via DF-PAGE.
AB  - Here we present a procedure for peptide fractionation by SDS-free polyacrylamide
      gel electrophoresis, based on discontinuous buffer systems. In the absence of
      SDS, peptide migration depends both on their molecular mass and on their net
      charge at the electrophoresis pH. By selecting the separation pH, peptide
      mobility is modulated. In the original discontinuous buffer system
      (Tris/glycine), peptides that migrate to the anode have pI values below 6.8 and
      distribute along the lane in a pI decreasing order, while at acidic pH, as that
      afforded by histidine/MOPS buffer system, peptides with pI below 5.5 are
      fractionated. Separation at acid pH is particularly useful for recovering
      phosphopeptides as well as other highly negatively charged peptides, as those
      containing sialic or sulfate substituents. Both separation conditions in
      Tris/glycine and in histidine/MOPS are applicable to proteomic studies, by dual
      fractionation polyacrylamide gel electrophoresis (DF-PAGE). First, complex
      protein samples are separated via SDS-PAGE, and after in-gel proteolysis,
      peptides are loaded on a second SDS-free gel, where they are separated as
      described here.

PMID- 22585488
TI  - Tris-acetate polyacrylamide gradient gels for the simultaneous electrophoretic
      analysis of proteins of very high and low molecular mass.
AB  - Polyacrylamide gel electrophoresis (PAGE) is one of the most powerful tools used
      for protein analysis. We describe the use of Tris-acetate buffer and 3-15%
      polyacrylamide gradient gels to simultaneously separate proteins in the mass
      range of 10-500 kDa. We show that this system is highly sensitive, it has good
      resolution and high reproducibility, and that it can be used for general
      applications of PAGE such as Coomassie Brilliant Blue staining and
      immunoblotting. Moreover, we describe how to generate mini Tris-acetate
      polyacrylamide gels to use them in miniprotein electrophoresis systems. These
      economical gels are easy to generate and to manipulate and allow a rapid analysis
      of proteins. All these features make the Tris-acetate-PAGE system a very helpful
      tool for protein analysis.

PMID- 22585489
TI  - SDS-PAGE for 35S immunoprecipitation and immunoprecipitation western blotting.
AB  - This report discusses recent methods of sample preparation and gel
      electrophoresis for (35)S immunoprecipitation (IP) and IP western blotting. In
      both methods, IP is used to obtain purified proteins, and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) is used to separate the proteins on
      a gel. In (35)S IP, the proteins are radiolabeled and visualized on film by
      fluorography; in IP blotting, proteins are transferred onto nitrocellulose paper,
      and antibodies are used to detect specific proteins. A similar IP and SDS-PAGE
      method can be used for both procedures, but IP blotting has the potential
      advantages of improvement in sensitivity for low-abundance proteins and enhanced
      specificity for identification of proteins from a mixture. Some of the technical
      adaptations discussed here to facilitate IP blotting and avoid loss of beads or
      purified proteins may also be useful for (35)S IP.

PMID- 22585490
TI  - Two-dimensional gel electrophoresis: vertical isoelectric focusing.
AB  - Two-dimensional gel electrophoresis (2-DE) is one of the most powerful tools for
      separating proteins based on their size and charge. 2-DE is very useful to
      separate two proteins with identical molecular weights but different charges,
      which cannot be achieved with just sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE). Here, a simpler and easier version of 2-DE is
      presented which is also faster than all the currently available techniques. In
      this modified version of 2-DE, isoelectric focusing is carried out in the first
      dimension using a vertical SDS-PAGE apparatus. Following the first-dimensional
      IEF, each individual lane is excised from the IEF gel and, after a 90 degrees 
      rotation, is inserted into a second-dimensional SDS-PAGE, which can be stained
      with Coomassie Brilliant Blue for protein analysis or immunoblotted for further
      analysis. This version of IEF can be run in less than 2 h compared to the
      overnight run required by O'Farrell's method. Difficult tube gel casting and gel
      extrusion as well as tube gel distortion are eliminated in our method. This
      method is simpler, faster, and inexpensive. Both dimensions can be done on the
      same SDS-PAGE apparatus, and up to ten samples can be run simultaneously using
      one gel.

PMID- 22585491
TI  - Isoelectric focusing in agarose gel for detection of oligoclonal bands in
      cerebrospinal and other biological fluids.
AB  - Isoelectric focusing (IEF) coupled with immunodetection (immunofixation or
      immunoblotting) has become the leading technique for the detection and study of
      oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) and also is increasingly
      used in other body fluids such as the tear and serum. Limited commercial
      availability of precast agarose IEF gels for research and a need for
      customization prompted reporting a detailed general protocol for the preparation
      and casting of agarose IEF gel along with sample, control, and isoelectric point
      marker preparation and carrying out the focusing itself for CSF OCBs. However,
      the method is readily adaptable to the use of other body fluid specimens and,
      possibly, research specimens such as culture fluids as well.

PMID- 22585492
TI  - Native flatbed isoelectric focusing for determining antibody clonotype
      distribution.
AB  - A sensitive method to analyze specific antibody clonotype changes in a patient
      with systemic lupus erythematosus, who developed autoantibodies to the Ro 60
      autoantigen under observation, is described in this chapter. Patient sera
      collected over several years were separated by flatbed isoelectric focusing
      (IEF). Following electrofocusing, the gel is now ready to be analyzed by affinity
      immunoblotting utilizing Ro 60-coated nitrocellulose membrane to determine
      oligoclonality of the anti-Ro 60-containing sera.

PMID- 22585493
TI  - Two-dimensional gel electrophoresis: glass tube-based IEF followed by SDS-PAGE.
AB  - The genome information combined with data derived from modern mass spectrometry
      enables us to determine the identity of a protein once it is isolated from a
      complex mixture. Two-dimensional gel electrophoresis established more than three
      decades ago serves as a powerful protocol to isolate many proteins at once for
      such protein analysis. In the first two decades, the original procedure to use a
      glass tube-based isoelectric focusing (IEF) had been commonly used. Since an IEF
      in glass tubes is rather difficult to maneuver, a new method to use an IEF on a
      thin agarose slab backed by a plastic film (IPG Dry Strip) has been invented and
      is now widely used. In this chapter, we describe the original protocol that uses
      a glass tube-based IEF because, the capacity of protein loading and resolving
      power of this type of classic two-dimensional gel is still indispensible.

PMID- 22585494
TI  - One-dimensional and two-dimensional immobilized metal affinity electrophoresis.
AB  - Immobilized metal affinity electrophoresis (IMAEP) is a straightforward method in
      which metal ions are embedded in a polyacrylamide gel strip with a negligible
      electrophoretic migration. Due to the preferential binding between metal ions and
      the phosphate group, this method uses immobilized metal ions like iron,
      manganese, aluminum, or titanium to capture phosphoproteins from a mixture of
      phosphoprotein and nonphosphoproteins. IMAEP has also been incorporated into a
      traditional two-dimensional (2D) sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE) system (isoelectric focusing-PAGE) to increase its
      resolving power. In 2D IMAEP, the metal ions in polyacrylamide gel strip are
      overlaid on top of the second dimensional polyacrylamide gel to stop
      electrophoretic migration of phosphoproteins. Data shows that there is no
      detrimental effect of SDS in IMAEP on the extraction of phosphoproteins from a
      mixture of proteins. In addition, SDS exposes phosphate groups by unfolding the
      phosphoproteins to facilitate metal ion-phosphate binding while supplying the
      protein with negative charges.

PMID- 22585495
TI  - Two-dimensional difference gel electrophoresis.
AB  - Two-dimensional difference gel electrophoresis (2D DIGE) is a modified form of 2D
      electrophoresis (2DE) that allows one to compare two or three protein samples
      simultaneously on the same gel. The proteins in each sample are covalently tagged
      with different color fluorescent dyes that are designed to have no effect on the
      relative migration of proteins during electrophoresis. Proteins that are common
      to the samples appear as "spots" with a fixed ratio of fluorescent signals,
      whereas proteins that differ between the samples have different fluorescence
      ratios. With the appropriate imaging system, difference gel electrophoresis
      (DIGE) is capable of reliably detecting as little as 0.2 fmol of protein, and
      protein differences down to +/-15%, over a ~20,000-fold protein concentration
      range. DIGE combined with digital image analysis therefore greatly improves the
      statistical assessment of proteome variation. Here we describe a protocol for
      conducting DIGE experiments, which takes 2-3 days to complete.

PMID- 22585496
TI  - Protein identification on archived 2-D gels.
AB  - Because of the availability of genome information combined with proteomics
      techniques, it is possible to determine the identity of a protein which had been
      isolated many years ago on a two-dimensional gel electrophoresis and stored in a
      dry state as a data archive. The protocol described in this chapter will assist
      researchers who want to know the identity of a protein separated decades ago when
      no techniques were available to determine the identity of the protein.

PMID- 22585497
TI  - Diagonal electrophoresis for the detection of protein disulfides.
AB  - Cysteines are one of the most rarely used amino acids in proteins, therefore when
      conserved in proteins they usually play critical roles in structure, function, or
      regulation of the protein. These cysteines or thiols can be reversibly oxidised
      to sulfenic acid (-SOH), thiyl radicals (-S) or nitrosothiols (-SNO) or form both
      inter-and intra-disulfide bridges (PSSP). The protein thiol groups PSSPs,
      represent a larger active redox pool than glutathione and are likely to be
      directly involved in cellular defence against oxidative stress. Diagonal
      electrophoresis is a relatively simple technique to analyze the formation of
      protein disulfides by sequential non-reducing/reducing electrophoresis. Proteins
      that do not form disulfides, electrophorese identically in both dimensions and
      form a diagonal after the second dimension, proteins that contained intra-chain
      disulfides lie above this diagonal, while those that formed inter-disulfides fall
      below the diagonal. This technique therefore allows for the detection and
      identification of protein disulfides.

PMID- 22585498
TI  - Two-dimensional blue native/SDS gel electrophoresis of multiprotein complexes.
AB  - The two-dimensional blue native/sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (2D BN/SDS-PAGE) is a method of choice for the investigation of
      protein complexes. This highly resolvent separation method is unique in that it
      facilitates the identification of many protein complexes simultaneously. Because
      of its simplicity and suitability, the 2D BN/SDS-PAGE can be now applied to a
      wide range of organisms, including bacteria, viruses, yeasts, animals, and
      plants. Moreover, recent modifications have made it possible to apply this method
      to the study of whole protein complexes of an organism. Here, we propose
      protocols for the investigation of the whole complexome of bacteria as well as
      eukaryotic cells.

PMID- 22585499
TI  - Immunoelectrophoresis: a method with many faces.
AB  - Immunoelectrophoresis (IEP) was the first practical method that combined
      electrophoresis and -immunoprecipitation for identifying and characterizing
      proteins within complex mixtures. Over the years, IEP has been extended to
      include a variety of techniques and, as a general name, has been applied to
      virtually any technique that involves electrophoresis and antigen-antibody
      precipitin reaction for proteins. Because of the diversity in technical details
      of different IEP versions, the method described here deals only with classic IEP.
      Although it requires some manual expertise, IEP is versatile, relatively easy to
      customize, and economical with no need for expensive instrumentation. Further, it
      can discern identity, partial identity, and nonidentity of the proteins. Any low
      viscosity body fluid specimen or, possibly, culture fluid and tissue extract
      could be tested with IEP if proper antibodies are available. With these
      attributes, classic IEP remains a valuable tool for clinical diagnostic testing,
      purity checking of biochemical and pharmaceutical products, and research.

PMID- 22585500
TI  - Cell surface protein biotinylation for SDS-PAGE analysis.
AB  - Cell surface proteins play a very important role in physiology and pathology and
      are receiving increased attention by the pharmaceutical industry as valuable
      targets for development of new therapeutics. However, owing to the very nature of
      this category of proteins, their comprehensive study remains an elusive task. A
      number of methods have been proposed to enrich and purify cell surface proteins.
      Among them, usage of biotinylating reagents and exploitation of the strong
      interaction between biotin and streptavidin for the purification of biotinylated
      proteins has rapidly gained in popularity and allowed some of the most
      significant progresses in quantitative proteomics. This chapter focuses on
      methods for cell surface biotinylation with commercially available reagents,
      capture by avidin-affinity chromatography and release of the biotinylated surface
      proteins for downstream analysis by electrophoretic techniques.

PMID- 22585501
TI  - A multichannel gel electrophoresis and continuous fraction collection apparatus
      for high-throughput protein separation and characterization.
AB  - We developed a multichannel gel electrophoresis system that continuously collects
      fractions as protein bands migrate off the bottom of gel columns. The device uses
      several short linear gel columns, each of a different percent acrylamide, to
      achieve a separation power similar to that of a long gradient gel. A "Counter
      Free-Flow" elution technique allows continuous and simultaneous fraction
      collection from multiple channels at low cost. Using the system with SDS-PAGE,
      300 MUg samples of protein can be separated and eluted into 48-96 fractions over
      a mass range of 10-150 kDa in 2.5 h. Each eluted protein can be recovered at 50%
      efficiency or higher in ~500 MUL. The system can also be used for native gel
      electrophoresis, but protein aggregation limits the loading capacity to about 50
      MUg per channel and reduces resolution. This system has the potential to be
      coupled with mass spectrometry to achieve high-throughput protein identification.

PMID- 22585502
TI  - Gel-absorption-based sample preparation method for shotgun analysis of membrane
      proteome.
AB  - Membrane proteins solubilized in a starting buffer containing high concentration
      of sodium dodecyl sulfate (SDS) are directly entrapped and immobilized into gel
      matrix when the membrane protein solution is absorbed by the vacuum-dried
      polyacrylamide gel. After the detergent and other salts are removed by washing,
      the proteins are subjected to in-gel digestion and the tryptic peptides are
      extracted and analyzed by CapLC-MS/MS. The newly developed method not only avoids
      protein loss and the adverse protein modifications during gel-embedment but also
      improves the subsequent in-gel digestion and the recovery of tryptic peptides,
      particularly the hydrophobic peptides. Thus, this method facilitates the
      identification of membrane proteins especially the integral membrane proteins.

PMID- 22585503
TI  - Interactions of hemoglobin in live red blood cells measured by the
      electrophoresis release test.
AB  - Electrophoresis release test (ERT) is the starch-agarose mixed gel
      electrophoresis of live red blood cells (RBCs). Mixed gel electrophoresis used to
      be one of the classic methods to isolate proteins, and in our laboratory, this
      technique is usually performed to isolate hemoglobins. Recently, combined with
      sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and liquid
      chromatography coupled with tandem mass spectrometry (LC/MS/MS), ERT has been
      used to study the interactions between hemoglobin and other proteins in live
      RBCs.

PMID- 22585504
TI  - Extraction of proteins from gels: a brief review.
AB  - Gel electrophoresis is an important methodology employed for protein analysis. It
      is often necessary to elute and recover proteins separated by sodium dodecyl
      sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The procedure involves
      localizing the protein of interest on the gel following SDS-PAGE, eluting the
      protein from the gel, removing SDS from the eluted sample, and finally renaturing
      the protein (enzymes, for example) for subsequent analysis. Proteins are
      extracted from gels by several methods. These include dissolution of the gel
      matrix, passive diffusion, and electrophoretic elution. Proteins eluted from gels
      have been used successfully in a variety of downstream applications, including
      protein chemistry, proteolytic cleavage, determination of amino acid composition,
      polypeptide identification by trypsin digestion and matrix-assisted laser
      desorption ionization-time of flight mass spectroscopy, as antigens for antibody
      production, identifying a polypeptide corresponding to an enzyme activity and
      other purposes. Protein yields ranging from nanogram levels to 100 MUg have been
      obtained.

PMID- 22585505
TI  - A new algorithm for the simulation of SDS 2D-PAGE datasets.
AB  - This chapter describes a new software for the generation of simulated realistic
      sodium dodecyl sulfate two-dimensional polyacrylamide gel electrophoresis (SDS 2D
      PAGE) images. In order to choose the simulation strategy to provide realistic 2D
      PAGE maps the statistical characteristics of such images were taken into account,
      such as the distributions of sizes, intensities, and volumes of the spots. Also,
      the low reproducibility typical of replicated SDS 2D-PAGE maps of the same sample
      was simulated. This approach can be used to generate simulated datasets useful in
      the development and performance evaluation of new classification and/or image
      analysis algorithms applied to two-dimensional electrophoresis datasets, given
      the usually small number of experimental replications available.

PMID- 22585506
TI  - Isolation of proteins from polyacrylamide gels.
AB  - Minute amounts of proteins are required for immunization of mice for the
      development of antibodies including monoclonal antibodies. Here, we describe a
      rapid procedure for the isolation of proteins from polyacrylamide gels after
      sodium dodecyl sulfate polyacrylamide gel electrophoresis in sufficient amounts
      for immunization of animals.

PMID- 22585507
TI  - Gel drying methods.
AB  - For some instances, protein gels need to be dried after SDS-PAGE, for example, if
      autoradiography should be performed from radioactive-labeled proteins after their
      separation on SDS-polyacrylamide gels. Another reason may be to simply store the
      gel in the laboratory book. Aside from expensive commercial solutions, especially
      for storage of the dried gel in the lab book, the simple and cheap drying
      protocol here presented may be sufficient.

PMID- 22585508
TI  - Long-term, buffer-less, wet gel storage in non-sealed polyethylene bags.
AB  - Electrophoresed gels are normally fixed, stained, destained, and dried. Drying is
      normally carried out with commercial gel dryers or by drying between two
      cellophane sheets held together by two acrylic frames. Here, we report that
      stained and destained gels (7.5, 10, or 15%, denaturing or native gels; 0.4 or
      1.5 mm in thickness) could be stored wet, unsealed, and without any storage
      buffer for several months at room temperature within flexible polyethylene bags
      without significant shrinking or protein diffusion. The gel remains hydrated
      because of the de facto sealing achieved by the polyethylene sheets (PS) adhering
      airtightly to the gel on either sides. The microsaturated environment generated
      by the thin film of water molecules trapped between the gel and the PS, along
      with the nonporous nature of the PS, apparently protects the gel from cracking as
      well as shrinking significantly. The intensity of stained proteins increased
      during storage probably from the slight gel shrinkage observed. Wet gel storage
      is useful (a) when low abundance protein spots from multiple two-dimensional
      electrophoresis gels have to be excised for in-gel tryptic digestion or
      electroelution and (b) for wet gel autoradiography. In addition to avoiding dryer
      contamination and saving drying time, these bags prevent the moist gel from
      sticking to X-ray film. Such storage could also prove useful for electrophoretic
      transfer of fixed and stained gels.

PMID- 22585509
TI  - A brief review of other notable electrophoretic methods.
AB  - The use of electrophoretic methodologies for use in qualitative and preparative
      purposes are commonly used in biological research and have been well established
      as an integral analytical tool for a long time in most research laboratories.
      Listed here are some of the more specialized innovations that have been developed
      in recent times for special purposes of study. These include micropreparative
      isoelectric focusing in liquid suspension, accelerated protease digestion by SDS
      PAGE, two-dimensional SDS-PAGE for membrane protein resolution, carbon nanotube
      modified page for resolution of complement C3, electrophoretic resolution of
      ultra-acidic proteomes in acidic media, and two-dimensional immunoelectrophoresis
      of pre-beta/alpha lipoprotein A-I in agarose. All these methods are briefly
      reviewed in this chapter.

PMID- 22585510
TI  - Protein stains and applications.
AB  - Staining of proteins separated on gels provides the basis for determination of
      the critical properties of these biopolymers, such as their molecular weight
      and/or charge. Detection of proteins on gels and blots require stains. These
      stains vary in sensitivity, ease of use, color, stability, versatility, and
      specificity. This review discusses different stains and applications with details
      on how to use the advantages and disadvantages of each stain. It also compiles
      some important points to be considered in imaging and evaluation. Commonly used
      colorimetric and fluorescent dyes for general protein staining, and
      posttranslational modification-specific detection methods are also discussed.

PMID- 22585511
TI  - Coomassie-Brilliant Blue staining of polyacrylamide gels.
AB  - Over the past, a series of staining procedures for proteins were published. The
      most commonly used staining dye for proteins is still Coomassie-Brilliant Blue.
      The major reason is Coomassie-Brilliant Blue staining is simple, fast, and
      sensitive. As Coomassie-Brilliant Blue is almost insoluble in water, a series of
      procedures including colloidal aqueous procedures were described.

PMID- 22585512
TI  - Accelerated Coomassie Blue staining and destaining of SDS-PAGE gels with
      application of heat.
AB  - Coomassie Brilliant Blue is commonly used for the detection of proteins in sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis, owing to its reliability and
      simplicity. Here, we report dramatically decreased protein staining and
      destaining time, as well as significantly increased detection sensitivity with
      the application of enhanced heat. The staining time was 5 min at 55, 62.5, or 70
      degrees C for a 1.5-mm gel, while it took 45, 45, and 20 min, respectively, for
      destaining. The staining time could be reduced to 1 min for a 0.8 mm gel stained
      at 65 degrees C, to 2 min at 60 degrees C and 5 min at 55 degrees C. The
      destaining of proteins analyzed on a 0.8 mm gel could be accomplished in 8, 15,
      and 20 min at 65, 60, and 55 degrees C, respectively. Application of heat, thus,
      enables proteins to be stained and destained rapidly, as well as enhancing
      detection sensitivity.

PMID- 22585513
TI  - Silver staining techniques of polyacrylamide gels.
AB  - Although the main application for polyacrylamide gels is the separation and
      subsequent blotting of proteins for immunodetection, there are tasks that need
      staining of proteins in the polyacrylamide gel. Several different staining
      techniques exist for protein staining in SDS gels that differ in their
      sensitivity, their expenditure of time, and other aspects. Still, silver staining
      is the most sensitive and reliable staining technique. Because this technique was
      developed in the 1970s, a huge number of variations exist. Therefore, we will
      provide herein three methods, which are robust and easy to perform.

PMID- 22585514
TI  - Revisit of imidazole-zinc reverse stain for protein polyacrylamide gel
      electrophoresis.
AB  - Imidazole-zinc reverse stain (ZN stain) is known for its high sensitivity, ease
      of use, and cost-effective feature. ZN stain is compatible to many experiments of
      which those are proteomics-related in particular. Here, we describe the ZN
      staining procedures and the subsequent procedures incorporated in detail, along
      with the improvements of setup in aspects of visualization and documentation for
      post-processing ZN-stained gel images.

PMID- 22585515
TI  - Counterion dye staining of proteins in one- and two-dimensional sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis and tryptic gel digestion of stained
      protein for mass spectrometry.
AB  - A fast and matrix-assisted laser desorption/ionization mass spectrometry
      compatible protein staining method in one- and two-dimensional sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis is described. It is based on the
      counterion dye staining method that employs oppositely charged two dyes, zincon
      and ethyl violet, to form an ion-pair complex. The protocol, including fixing,
      staining, and quick washing steps, can be completed in 1-1.5 h, depending upon
      gel thickness. It has the sensitivity comparable to the colloidal Coomassie
      Brilliant Blue G stain using phosphoric acid as a component of staining solution
      (4-8 ng). The counterion dye stain does not induce protein modifications that
      complicate interpretation of peptide mapping data from mass spectrometry.
      Considering the speed, sensitivity, and compatibility with mass spectrometry, the
      counterion dye stain may be more practical than any other dye-based protein
      stains for routine proteomic researches.

PMID- 22585516
TI  - TEMED-enhanced photoluminescent imaging of human serum proteins by quantum dots
      after PAGE.
AB  - Polyacrylamide gel electrophoresis (PAGE) has been one of the most powerful and
      widely used separation techniques for complex biological samples, whose
      traditional detection methods include organic dye or silver staining. As a
      simple, convenient, and ultrasensitive detection of proteins for PAGE, a novel
      enhanced photoluminescent (PL) imaging method was developed. Thioglycolic acid
      (TGA)-capped CdTe quantum dots (QDs) and the enhanced reagent of
      tetramethylethylenediamine (TEMED) are introduced, achieving the direct detection
      of various proteins in native 1-DE, 2-DE, and SDS gels. Here, we describe the
      general protocol of TEMED-enhanced PL imaging by QDs, including materials,
      practical procedures, as well as some notes.

PMID- 22585517
TI  - Microwave-assisted protein staining, destaining, and in-gel/in-solution digestion
      of proteins.
AB  - Rapid evolution of state-of-the-art proteomic analyses has encompassed
      development of high-throughput analytical instrumentation and bioinformatic
      tools. However, recently, there has been a particular emphasis on increasing the
      throughput of sample preparation, which has become one of the rate-limiting steps
      in protein characterization workflows. Researchers have been investigating
      alternative methods to conventional convection oven incubations to try and reduce
      sample preparation time for protein characterization. Several protocols have
      appeared in the literature, which employ microwave irradiation as a tool for the
      preparation of biological samples for subsequent characterization by a variety of
      analytical techniques. In this chapter, techniques for microwave-assisted protein
      staining, destaining, and digestion are described. In general, the application of
      microwave-assisted technologies resulted in the drastic reduction of overall
      sample preparation time, though discrepancies in the reproducibility of several
      published digestion protocols still remain to be clarified.

PMID- 22585518
TI  - Electrophoretic separation and detection of metalloproteins by X-ray fluorescence
      mapping.
AB  - All living systems depend on metalloproteins. Yet, while tools for the separation
      and identification of apo-proteins are well developed, those enabling
      identification and quantitation of individual metalloproteins within complex
      mixtures are still nascent. Here, we describe the electrophoretic separation of a
      mixture of carbonic anhydrase, ceruloplasmin, urease, and hemoglobin using native
      2D gel electrophoresis and X-ray fluorescence mapping-an approach we have
      developed to be broadly applicable, not require specialized equipment for sample
      preparation, and likely to be extensible in the future.

PMID- 22585519
TI  - Fluorescent staining of gels.
AB  - Certain transition metal complexes show intensive fluorescence when bound to
      proteins. They can be used to stain gels after electrophoresis with a sensitivity
      approaching that of silver staining, but in a much simpler and more reproducible
      procedure. Stains can be prepared easily and at a fraction of the cost of
      commercially available reagents.Hydrophobic dyes can be used to stain gels
      without fixing; they do not interfere with later blotting or electro-elution.

PMID- 22585520
TI  - A single-step simultaneous protein staining procedure for polyacrylamide gels and
      nitrocellulose membranes by Alta during western blot analysis.
AB  - A simple method for staining of proteins simultaneously on sodium dodecyl sulfate
      (SDS) polyacrylamide gels and nitrocellulose membranes by Alta during western
      blot analysis is described. A 5% solution of Alta, a commercially available
      cosmetic preparation, is added in the upper tank buffer during electrophoresis.
      On completion of electrophoresis, the gel is washed in distilled water and viewed
      on a white light plate and a transilluminator to photograph the protein profiles.
      The gel is processed for western blot transfer of proteins onto a nitrocellulose
      membrane, and upon completion, the protein profiles on the membrane are viewed
      and photographed as stated above. The membrane can then be processed for
      immunostaining as per the standard procedure. Thus, the staining procedure using
      Alta is simple, rapid (without any need of destaining), and cost-effective.

PMID- 22585521
TI  - Detection of glycoproteins in polyacrylamide gels using Pro-Q Emerald 300 dye, a
      fluorescent periodate Schiff-base stain.
AB  - Pro-Q Emerald 300 glycoprotein stain generates a bright-green fluorescent signal
      upon reacting with periodic acid-oxidized carbohydrate groups on proteins. With
      this dye, it is possible to detect proteins directly in the gel without the need
      to transfer them to a membrane. This dye is more sensitive than the standard
      periodic acid Schiff's base which uses acidic fuchsin dye.

PMID- 22585522
TI  - Spicy SDS-PAGE gels: curcumin/turmeric as an environment-friendly protein stain.
AB  - Gel proteins are commonly stained with calorimetric/fluorescent dyes. Here, we
      demonstrate that heat-solubilized curcumin can serve as a nontoxic and
      environment-friendly fluorescent/colorimetric reversible protein stain. Curcumin,
      the yellow pigment found in the rhizomes of the perennial herb Curcuma longa
      (turmeric), is insoluble in aqueous solvents. However, heat (100 degrees C)
      solubilization in water renders 1.5% of curcumin soluble. Curcumin solubilized by
      ethanol or alkali is ineffective in staining proteins. Heat solubilized curry
      spice turmeric stains proteins similarly. Staining is achieved in 30 min, with a
      sensitivity almost equaling that of Coomassie Brilliant Blue (CBB). Destaining is
      not required, and excess curcumin/turmeric can be discarded into the sink.
      Binding of proteins by silver inhibits curcumin binding, suggesting similarity of
      protein binding by silver and curcumin. It costs $1.5-2.0 to stain a mini-gel
      with curcumin, while turmeric costs less than 0.005 cent. CBB staining/destaining
      costs about 2 cents. However, CBB is toxic and its use necessitates specialized
      disposal efforts. Curcumin/turmeric, thus, can serve as an ideal nontoxic protein
      stain.

PMID- 22585523
TI  - In-gel staining of proteins in native polyacrylamide gel electrophoresis using
      meso-tetrakis(4-sulfonatophenyl) porphyrin.
AB  - Protein identification in polyacrylamide gel electrophoresis (PAGE) requires post
      electrophoretic steps like fixing, staining, and destaining of the gel, which are
      time-consuming and cumbersome. A new method for direct visualization of protein
      bands in PAGE has been developed using meso-tetrakis(4-sulfonatophenyl)porphyrin
      (TPPS) as a dye without the need for any post-electrophoretic steps; thus,
      separation and recovery of enzymes become much easier for further analysis.
      Activity staining was carried out to show that the biochemical activity of the
      enzymes was preserved after electrophoresis.

PMID- 22585524
TI  - Rapid detection of proteins in polyacrylamide electrophoresis gels with Direct
      Red 81 and Amido Black.
AB  - Proteins separated by SDS-polyacrylamide gel electrophoresis need to be stained
      with organic dyes to be visualized and to enable comparisons to be made between
      the intensity of protein bands to observe and determine differences in protein
      concentration. The standard protein staining is with Coomassie Blue R-250.
      Coomassie staining takes 1 h to complete. Direct Red 81 and Amido Black stain
      proteins within 10 min. This chapter describes Direct Red 81 and Amido Black
      staining in comparison to staining with Coomassie Blue R-250.

PMID- 22585525
TI  - Zymographic assay of oxidases using peroxidase or hemin entrapped in
      polyacrylamide gel.
AB  - This chapter describes a zymographic assay of oxidases which is based on a
      coupled peroxidase or hemin reaction. The enzymatic activity of oxidases (i.e.,
      diamine oxidase/DAO, glucose oxidase, galactose oxidase) can be directly
      monitored on polyacrylamide gels containing horseradish peroxidase or hemin, in
      the presence of their specific substrates and ortho-phenylenediamine (OPDA), an
      oxidizable chromogen. In the presence of hydrogen peroxide, OPDA is oxidized to
      azo-aniline, which led to well-defined yellow-brown bands on gels, with
      intensities corresponding to the enzymatic activity of oxidases.

PMID- 22585526
TI  - Coomassie Brilliant Blue removal/disposal from gel destain and used gel stain in
      an environment-friendly manner.
AB  - Toxic reagents are employed to destain Coomassie Brilliant Blue (CBB) stained
      gels. We tested the efficacy of various paper adsorbents in adsorbing CBB
      released from gels during destaining. Kimwipes were the most efficient, followed
      by Teri towels, multifold towels, and Whatman (numbers 1 and 3) filter papers.
      Three Kimwipes added during destaining of a CBB-stained mini-gel helped adsorb
      the released dye. Thus, stain removal with Kimwipes helps reduce destain use and
      organic waste accumulation, enables recycling of nonradioactive destaining
      solution, and is 7.5-fold cheaper than an available method for CBB disposal.
      Next, we used Kimwipes to deplete the dye from a used CBB staining solution
      awaiting proper disposal by our Institutional Safety Office. Seventy-five
      Kimwipes successfully helped remove the dye from a 0.05% CBB staining solution in
      5 to 10 min. The blue-colored Kimwipes did not release the stain even when
      squeezed dry after incubation in various salts, water, or acid solutions for five
      weeks. The CBB removed thus can be simply disposed as solid waste and will not
      leach out from solid landfills. Kimwipes, thus, enables CBB disposal in an
      environmentally friendly manner and allows recycling of destaining solution.

PMID- 22585527
TI  - A brief review of other notable protein detection methods on acrylamide gels.
AB  - Several methods have been described to stain proteins analyzed on acrylamide
      gels. These include ultrasensitive protein detection in one-dimensional and two
      dimensional gel electrophoresis using a fluorescent product from the fungus
      Epicoccum nigrum; a fluorescence-based Coomassie Blue protein staining;
      visualization of proteins in acrylamide gels using ultraviolet illumination;
      fluorescence visualization of proteins in sodium dodecyl sulfate-polyacrylamide
      gels using environmentally benign, nonfixative, saline solution; and increasing
      the sensitivity four- to sixfold for detecting trace proteins in dye or silver
      stained polyacrylamide gels using polyethylene glycol 6000. All these methods are
      reviewed briefly in this chapter.

PMID- 22585528
TI  - Ultrasensitive protein detection and imaging: comparison of LumiteinTM,
      ProteoSilverTM, SYPRO((r)) Ruby, and Coomassie ((r)) Brilliant Blue gel stains.
AB  - Following sodium dodecyl sulfate polyacrylamide gel electrophoresis, proteins can
      be visualized by various methods of detection and imaging. Traditional methods of
      protein gel detection and imaging have been improved and expanded through
      technological advancement. Today, the detection of proteins, resolved on gels,
      can be accomplished with a variety of stains with various sensitivities. Digital
      cameras used in the imaging of protein gels are not only more sensitive than
      their film precursors, but they can be used in combination with imaging software
      that offers a host of useful applications. Here we describe the UVP BioImaging
      System in combination with LabWorks Image and Acquisition software to provide a
      comparison of four different protein gel stains: LumiteinTM, ProteoSilverTM,
      SYPRO((r)) Ruby, and Coomassie((r)) Brilliant Blue. We demonstrate that the
      detection sensitivity limit appears to be between 100 and 500 ng/protein band of
      protein with Coomassie((r)) Brilliant Blue, 10-50 ng/protein band with LumiteinTM
      and SYPRO((r)) Ruby, and as little as 5 ng/protein band with the ProteoSilverTM
      stain.

PMID- 22585529
TI  - Common artifacts and mistakes made in electrophoresis.
AB  - Proteases that act at room temperature upon proteins in the sample buffer prior
      to heating, cleavage of the Asp-Pro bond upon prolonged heating of proteins at
      high temperatures, contamination of sample or sample buffer with keratin,
      leaching of chemicals from disposable plasticware, contamination of urea with
      ammonium cyanate are some subtle artifacts that can have significant deleterious
      effects on carefully planned and executed experiments. In addition, researchers
      are culpable of committing mistakes with respect to (a) calculating the cross
      linking factor of a gel, (b) polymerization temperature and time for a
      polyacrylamide gel, (c) inducing aggregates in samples for electrophoresis, (d)
      titrating the running buffer in electrophoresis, (e) proper sample preparation,
      (f) amount of protein to be loaded on a gel, (g) sample buffer-to-protein ratios,
      (h) incompletely removing phosphate buffered saline from cells prior to cell
      lysis and (i) overfocusing of IPG strip in two-dimensional gel electrophoresis.
      Taking proper heed to all these factors can greatly help generate perfect
      experimental results.

PMID- 22585530
TI  - Patient's assessment of discomfort during ultrasound-guided injection of Morton's
      neuroma: selecting the optimal approach.
AB  - PURPOSE: Assess patient discomfort during two different methods of injection of
      Morton's neuroma. METHODS: Sixty-eight patients referred for ultrasound-guided
      injection of Morton's neuroma had punctures performed dorsal or plantar to the
      interdigital skin crease, with and without preliminary subcutaneous local
      anesthesia (LA). Patients rated discomfort during skin puncture (SP) and needle
      advancement (NA) using a visual analog scale. RESULTS: Average pain score was 4.4
      +/- 2.3 (1 SD) for the plantar approach and 2.9 +/- 2.0 for the dorsal approach.
      This difference was statistically significant during SP (p < 0.01) and NA (p <
      0.05). During the plantar approach with LA, mean pain score during SP was 4.4 (+/
      2.1) and 3.9 (+/- 2.8) during NA. This plantar approach without LA resulted in a
      pain score of 4.3 (+/- 2.6) and 3.8 (+/- 3.1), respectively. Mean pain scores for
      patients injected from the dorsal approach with LA during SP were 3.8 (+/- 2.7)
      and NA were 2.2 (+/- 2.0) and without LA were 2.6 (+/- 1.9) and 3.0 (+/- 2.1).
      There was no statistical significance in mean pain score difference during SP and
      NA, with and without LA for either the plantar (p > 0.05) or the dorsal (p >
      0.05) approach. CONCLUSIONS: Injection of Morton's neuroma was better tolerated
      via a dorsal approach and use of preliminary LA did not confer any benefit.

PMID- 22585531
TI  - Confirmation of the Zechi-Ceide syndrome.
AB  - Atretic cephaloceles associated with multiple congenital anomalies are known to
      follow either autosomal dominant or autosomal recessive patterns of inheritance.
      Zechi-Ceide syndrome (OMIM 612916) is an autosomal recessive disorder,
      characterized by an occipital atretic cephalocele, characteristic facial
      features, and large feet. Here we describe a patient with findings fitting Zechi
      Ceide syndrome, in whom some of the manifestations were also present in his
      mother, indicating either autosomal dominant inheritance with variable
      expression, X-linked inheritance, or a manifesting carrier of an autosomal
      recessive inheritance.

PMID- 22585532
TI  - Immunologic response after laparoscopic colon cancer operation within an enhanced
      recovery program.
AB  - OBJECTIVE: It has been demonstrated that colon operation combined with fast-track
      (FT) surgery and laparoscopic technique can shorten the length of hospital stay,
      accelerate recovery of intestinal function, and reduce the occurrence of post
      operative complications. However, there are no reports regarding the combined
      effects of FT colon operation and laparoscopic technique on humoral inflammatory
      cellular immunity. METHODS: This was a prospective, controlled study. One hundred
      sixty-three colon cancer patients underwent the traditional protocol and open
      operation (traditional open group, n=42), the traditional protocol and
      laparoscopic operation (traditional laparoscopic group, n=40), the FT protocol
      and open operation (FT open group, n=41), or the FT protocol and laparoscopic
      operation (FT laparoscopic group, n=40). Blood samples were taken prior to
      operation as well as on days 1, 3, and 5 after operation. The number of
      lymphocyte subpopulations was determined by flow cytometry, and serum interleukin
      6 and C-reactive protein levels were measured. Post-operative hospital stay, post
      operative morbidity, readmission rate, and in-hospital mortality were recorded.
      RESULTS: Compared with open operation, laparoscopic colon operation effectively
      inhibited the release of post-operative inflammatory factors and yielded good
      protection via post-operative cell immunity. FT surgery had a better protective
      role with respect to the post-operative immune system compared with traditional
      peri-operative care. Inflammatory reactions, based on interleukin-6 and C
      reactive protein levels, were less intense following FT laparoscopic operation
      compared to FT open operation; however, there were no differences in specific
      immunity (CD3+ and CD4+ counts, and the CD4+/CD8+ ratio) during these two types
      of surgical procedures. Post-operative hospital stay in patients randomized to
      the FT laparoscopic group was significantly shorter than in the other three
      treatment groups (P<0.01). Post-operative complications in patients who underwent
      FT laparoscopic treatment were less than in the other three treatment groups
      (P<0.05). There were no significant differences between the four treatment groups
      regarding readmission rate and in-hospital mortality. CONCLUSIONS: The
      laparoscopic technique and FT surgery rehabilitation program effectively
      inhibited release of post-operative inflammatory factors with a reduction in peri
      operative trauma and stress, which together played a protective role on the post
      operative immune system. Combining two treatment measures during colon operation
      produced better protective effects via the immune system. The beneficial clinical
      effects support that the better-preserved post-operative immune system may also
      contribute to the improvement of post-operative results in FT laparoscopic
      patients.

PMID- 22585533
TI  - beta-Eudesmol induces JNK-dependent apoptosis through the mitochondrial pathway
      in HL60 cells.
AB  - beta-eudesmol, a natural sesquiterpenol present in a variety of Chinese herbs, is
      known to inhibit the proliferation of human tumor cells. However, the molecular
      mechanisms of the effect of beta-eudesmol on human tumor cells are unknown. In
      the present study, we report the cytotoxic effect of beta-eudesmol on the human
      leukemia HL60 cells and its molecular mechanisms. The cytotoxic effect of beta
      eudesmol on HL60 cells was associated with apoptosis, which was characterized by
      the presence of DNA fragmentation. beta-eudesmol-induced apoptosis was
      accompanied by cleavage of caspase-3, caspase-9, and poly (ADP-ribose)
      polymerase; downregulation of Bcl-2 expression; release of cytochrome c from
      mitochondria; and decrease in mitochondrial membrane potential (MMP). Activation
      of c-Jun N-terminal kinases (JNK) mitogen-activated protein kinases was observed
      in beta-eudesmol-treated HL60 cells, and the inhibitor of JNK blocked the beta
      eudesmol-induced apoptosis, downregulation of Bcl-2, and the loss of MMP. These
      data suggest that beta-eudesmol induces apoptosis in HL60 cells via the
      mitochondrial apoptotic pathway, which is controlled through JNK signaling.

PMID- 22585534
TI  - Avidity determines T-cell reactivity in abacavir hypersensitivity.
AB  - The antiretroviral drug abacavir (abc) elicits severe drug hypersensitivity
      reactions in HLA-B*5701(+)  individuals. To understand the abc-specific
      activation of CD8(+)  T cells, we generated abc-specific T-cell clones (abc
      TCCs). Abc reactivity could not be linked to the metabolism and/or processing of
      the drug, since abc metabolizing enzymes were not expressed in immune cells and
      inhibition of the proteasome in APCs did not affect TCC reactivity. Ca(2+) 
      influx assays revealed different reactivity patterns of abc-TCCs. While all TCCs
      reacted to abc presented on HLA-B*5701 molecules, a minority also reacted
      immediately to abc in solution. Titration experiments showed that the ability to
      react immediately to abc correlated significantly with the TCR avidity of the T
      cells. Modifications of soluble abc concentrations revealed that the reactivity
      patterns of abc-TCCs were not fixed but dynamic. When TCCs with an intermediate
      TCR avidity were stimulated with increasing abc concentrations, they showed an
      accelerated activation kinetic. Thus, they reacted immediately to the drug,
      similar to the reaction of TCCs of high avidity. The observed immediate
      activation and the noninvolvement of the proteasome suggest that, in contrast to
      haptens, abc-specific T-cell stimulation does not require the formation of
      covalent bonds to produce a neo-antigenic determinant.

PMID- 22585535
TI  - Monocytes as effector cells: activated Ly-6C(high) mouse monocytes migrate to the
      lymph nodes through the lymph and cross-present antigens to CD8+ T cells.
AB  - Monocytes have the capacity to differentiate into macrophages or dendritic cells
      (DCs) after extravasation into lymphoid and nonlymphoid tissues. They have thus
      been consequently considered as precursors, but not effector cells, recirculating
      exclusively through the blood. In this report, we demonstrate for the first time
      that, after subcutaneous injection, activated monocytes migrate through the
      lymphatics from the dermis into the draining lymph nodes by a CCR7-dependent
      mechanism. LPS-activated monocytes were less efficient than DCs in stimulating
      CD4(+)  T cells, but unexpectedly, they were highly efficient in inducing antigen
      specific CD8(+)  T-cell proliferation by cross-presentation, both in vitro and in
      vivo. Interestingly, CD8(+)  T cells stimulated in vivo by activated monocytes
      expressed a high level of CD62L, suggesting that they had undergone an
      unconventional activation process. In conclusion, our data strongly support the
      concept that monocytes can behave not only as precursor cells for macrophages and
      DCs, but also as effector cells with the capacity to migrate from the periphery
      to the lymph nodes through the lymph and to cross-present antigens to CD8(+)  T
      cells. These results suggest that monocytes can play an important role in the
      induction and regulation of CD4(+)  and CD8(+)  T-cell responses.

PMID- 22585536
TI  - Shape analysis of the corpus callosum and cerebellum in female MS patients with
      different clinical phenotypes.
AB  - The aim of this study was to investigate the shape differences in the corpus
      callosum (CC) and cerebellum of female relapsing-remitting multiple sclerosis
      (RRMS) and secondary progressive multiple sclerosis (SPMS) patients compared with
      healthy controls. This study was conducted using the magnetic resonance imaging
      scans of 15 control subjects, 26 RRMS, and 14 SPMS patients. The data obtained
      from the landmark coordinates were analyzed with statistical shape analysis. The
      landmarks that were chosen to determine the shape differences of the CC and
      cerebellum have been identified and used in previous studies. In addition to
      these landmarks, constructed landmarks were determined and used to assess
      regional shape differences better. The shapes of the CC and cerebellum showed
      statistically significant differences from the controls when compared with both
      the RRMS and SPMS patients. It was found that the deformation observed from
      controls to SPMS was greater than the deformation from controls to RRMS, both for
      the CC and cerebellum. In conclusion, this study revealed CC and cerebellar shape
      change in RRMS and SPMS, and showed that deformations both in CC and cerebellum
      advances with the disease progression.

PMID- 22585537
TI  - [Primary and secondary glomerular diseases].

PMID- 22585538
TI  - Time-dependent changes of oxime K027 concentrations in different parts of rat
      central nervous system.
AB  - The blood-brain barrier plays a vital role in the protection of the central
      nervous system. It is composed of endothelial cells with tight-junctions to limit
      the penetration of many endogenous and exogenous compounds, particularly
      hydrophilic xenobiotics. Nerve agents and pesticides are groups of compounds with
      high penetration potential into the central nervous system. However, oxime type
      antidotes are known to penetrate blood-brain barrier only in low concentration.
      The aim of presented study is to describe the pharmacokinetic profile of oxime
      K027 a novel antidote candidate. The main focus is on penetration of tested
      substance into the selected brain regions following time-dependent manner. The
      maximum concentration of the oxime K027 was attaining 15 and 30 min after i.m.
      application in plasma and brain tissue, respectively. The perfused brain tissue
      concentration was relatively high (10(-7) M order of magnitude) and depending on
      the brain region it was constant 15-60 min after application. The highest
      concentration was found in the frontal cortex 15 min after application while the
      lowest measured concentration was determined in the basal ganglia. This study
      showed that oxime K027 is able to achieve high concentration level in perfused
      brain tissue relatively quickly, but also demonstrated rapid clearance from the
      central nervous system. These results are probably due to low overall uptake of
      oxime K027 into the brain.

PMID- 22585539
TI  - Modeling nicotine dependence: an application of a longitudinal IRT model for the
      analysis of adolescent nicotine dependence syndrome scale.
AB  - INTRODUCTION: Measures of nicotine dependence typically use the item average or
      total score from rating scales, such as the Nicotine Dependence Syndrome Scale
      (NDSS). Alternatively, item response theory (IRT) methods can provide useful item
      specific information. IRT methods developed for longitudinal data can
      additionally provide information about item-specific changes over time. METHODS:
      We describe a longitudinal 2-parameter ordinal IRT model, and compare the results
      from this model with those from an IRT model for only the baseline item
      responses, and a conventional longitudinal analysis of the item-average NDSS
      score. We examined a 10-item, adolescent version of the NDSS at baseline, 6, 15,
      and 24 months for 1,097 9th or 10th graders. RESULTS: IRT analysis of the
      baseline data revealed that the items "willing to go out of the house in a storm
      to find a cigarette," "choose to spend money on cigarettes than lunch," "function
      better after morning cigarette," and "worth smoking in cold or rain," were good
      items at distinguishing individuals' levels of nicotine dependency. While the
      analysis of the averaged NDSS score indicated linear growth over time, the
      longitudinal IRT method revealed that only 5 out of the 10 items showed
      statistical increase over time. CONCLUSIONS: Infrequently endorsed NDSS items
      were generally better able to distinguish higher levels of dependency. The
      endorsement of such items increased over time. Items that changed significantly
      over time reflected the general drive concept of dependence, as well as the total
      first overarching dimension of dependence.

PMID- 22585540
TI  - Delineating a relationship between problematic anger and cigarette smoking: a
      population-based study.
AB  - BACKGROUND: Research implicates a potentially important relationship between
      anger and smoking, though extant work suffers from a number of limitations,
      including the absence of controls for psychiatric comorbidity and the use of
      treatment-seeking samples. The current study sought to examine the unique
      associations between problematic anger and smoking behavior in a large
      representative sample. METHODS: Participants included 5,692 adults from the
      National Comorbidity Survey-Replication, a nationally representative survey.
      Assessments of psychiatric diagnoses, smoking behavior, and problematic anger
      were administered. RESULTS: Results indicated that problems of anger experience
      were significantly associated with past-year daily smoking, heavy smoking, and
      nicotine dependence. After controlling for demographics and psychiatric
      comorbidity, anger experience was uniquely associated with each of these
      outcomes. Anger experience also was uniquely associated with lifetime history of
      smoking cessation failure. CONCLUSIONS: Overall, these population-based data
      suggest an important relationship between problematic anger and numerous aspects
      of smoking behavior.

PMID- 22585541
TI  - Determination of nicotine absorption from multiple tobacco products and nicotine
      gum.
AB  - INTRODUCTION: Snus is a smokeless tobacco product traditionally used in
      Scandinavia and available in pouched or loose forms. The objective of this study
      was to determine nicotine absorption for current pouched and loose snus products
      in comparison with a cigarette and an over-the-counter nicotine gum. METHODS: We
      conducted an open-label, randomized, 6-way, crossover study involving 20 healthy
      snus and cigarette users. One of 6 products (2 pouched snus, 2 weights of loose
      snus, a cigarette, and a nicotine gum) was administered at each of 6 visits.
      Blood samples were taken at intervals over 120 min and sensory perception
      assessed by questionnaire. RESULTS: For the 4 smokeless tobacco products and the
      nicotine gum, blood plasma levels of nicotine were ranked according to total
      nicotine content as follows: loose snus (27.1 mg nicotine) > pouched snus (14.7
      mg nicotine) > loose snus (10.8 mg nicotine) = pouched snus (10.7 mg nicotine) >
      nicotine gum (4.2 mg nicotine). The area under the plasma concentration-time
      curve (AUC) and maximum plasma concentration (C(max)) of nicotine ranged from
      26.9 to 13.1 ng.h/ml and 17.9 to 9.1 ng.h/ml, respectively across all the
      products. Nicotine was absorbed more rapidly from the cigarette but systemic
      exposure was within the range of the smokeless tobacco products (AUC = 14.8
      ng.h/ml; C(max) = 12.8 ng.h/ml). CONCLUSIONS: This study has generated new
      information on comparative nicotine absorption from a cigarette, loose snus, and
      pouched snus typical of products sold in Scandinavia. The similar nicotine
      absorption for 1 g portions of loose and pouched snus with approximately 11 mg of
      nicotine indicate that absorption kinetics were dependent on quantity of tobacco
      by weight and total nicotine content rather than product form.

PMID- 22585542
TI  - Nanomechanical properties of single amyloid fibrils.
AB  - Amyloid fibrils are traditionally associated with neurodegenerative diseases like
      Alzheimer's disease, Parkinson's disease or Creutzfeldt-Jakob disease.  However,
      the ability to form amyloid fibrils appears to be a more generic property of
      proteins. While disease-related, or pathological, amyloid fibrils are relevant
      for understanding the pathology and course of the disease, functional amyloids
      are involved, for example, in the exceptionally strong adhesive properties of
      natural adhesives. Amyloid fibrils are thus becoming increasingly interesting as
      versatile nanobiomaterials for applications in biotechnology. In the last decade
      a number of studies have reported on the intriguing mechanical characteristics of
      amyloid fibrils. In most of these studies atomic force microscopy (AFM) and
      atomic force spectroscopy play a central role. AFM techniques make it possible to
      probe, at nanometer length scales, and with exquisite control over the applied
      forces, biological samples in different environmental conditions. In this review
      we describe the different AFM techniques used for probing mechanical properties
      of single amyloid fibrils on the nanoscale. An overview is given of the existing
      mechanical studies on amyloid. We discuss the difficulties encountered with
      respect to the small fibril sizes and polymorphic behavior of amyloid fibrils. In
      particular, the different conformational packing of monomers within the fibrils
      leads to a heterogeneity in mechanical properties. We conclude with a brief
      outlook on how our knowledge of these mechanical properties of the amyloid
      fibrils can be exploited in the construction of nanomaterials from amyloid
      fibrils.

PMID- 22585543
TI  - Enhancing patient participation in oncology consultations: a best evidence
      synthesis of patient-targeted interventions.
AB  - OBJECTIVE: Because of the complexity of cancer consultations, the contribution of
      patients is often limited. This systematic review examined the characteristics
      and effectiveness of patient-targeted interventions that aim to enhance cancer
      patients' participation in the consultation. METHODS: Relevant studies were
      selected by a search of databases until mid-2010 (Pubmed, PsycINFO and CINAHL),
      citations in relevant reviews as well as backward/forward citations. A Best
      Evidence Synthesis was performed, taking into account the quality of studies.
      RESULTS: A total of 52 publications were included, describing 46 studies and 30
      unique interventions. One-third was delivered through either written or
      multimedia material, two-thirds face to face. Most originated from English
      speaking countries. Half targeted heterogeneous cancer populations, one-third
      targeted women with breast cancer. Half focussed on initial treatment-planning
      consultations. Overall, there was evidence for an effect on observed patient
      participation. There was no evidence for an effect on patient or doctor
      satisfaction and insufficient evidence for an effect on psychological well-being,
      physical well-being and consultation duration. The findings turned out to be
      largely independent of study quality. CONCLUSIONS: Effect of the interventions
      could only be demonstrated for immediate outcomes, that is, behaviour observed in
      the consultation. Implications for future research are discussed, including
      attention for gaps in the literature as well as the choice of outcome measures.

PMID- 22585544
TI  - Delineation of the interstitial 6q25 microdeletion syndrome: refinement of the
      critical causative region.
AB  - Interstitial deletions of the long arm of chromosome 6 are rare. Clinically, this
      is a recognizable microdeletion syndrome associated with intellectual disability
      (ID), acquired microcephaly, typical dysmorphic features, structural anomalies of
      the brain, and nonspecific multiple organ anomalies. Most of the reported cases
      have cytogenetically visible interstitial deletions or subtelomeric
      microdeletions. We report on a boy with global developmental delay, distinct
      dysmorphic features, dysgenesis of the corpus callosum, limb anomalies, and
      genital hypoplasia who has a small interstitial deletion of the long arm of
      chromosome 6 detected by comparative genomic hybridization (CGH). The deleted
      region spans around 1 Mb of DNA and contains only two coding genes, ARID1B and
      ZDHHC14. To the best of our knowledge, this case represents the typical phenotype
      with the smallest deletion reported so far. We discuss the possible role of these
      genes in the phenotypic manifestations.

PMID- 22585545
TI  - Galanin expression in the mouse major pelvic ganglia during explant culture and
      following cavernous nerve transection.
AB  - Autonomic neurons commonly respond to injury/axotomy with an increased expression
      of neuropeptides including galanin and pituitary adenylyl cyclase-activating
      polypeptide (PACAP). The increased peptide expression may enhance neuronal
      survival and axonal regeneration. Using quantitative (Q) PCR and
      immunocytochemistry, the present study tested whether galanin expression
      increased in male mouse major pelvic ganglia (MPG) neurons in response to injury.
      Galanin transcript expression increased significantly in MPG neurons following 72
      h in explant culture and 72 h after unilateral transection of the cavernous
      nerve. Under both conditions, the increase in galanin transcript levels was
      greater than the increase in PACAP transcript levels. In control MPG, galanin-IR
      nerve fibers formed pericellular arrangements around MPG neurons although few
      galanin-IR cells were evident and many of the galanin-IR cells may be small
      intensely fluorescent (SIF) cells. In 3-day-cultured MPGs, many more galanin-IR
      cells and nerve fibers were noted. The increased galanin expression was most
      apparent in neurons that were also immunoreactive for neuronal nitric oxide
      synthase, rather than tyrosine hydroxylase. Some explant-cultured MPG neurons
      exhibited immunoreactivity to galanin and PACAP. As reported previously for
      PACAP, there is an injury-induced increase in MPG galanin expression, which
      occurs preferentially in the parasympathetic postganglionic neurons.

PMID- 22585547
TI  - Contaminant hepatotoxins as culprits for kava hepatotoxicity--fact or fiction?
AB  - The culprit of kava hepatotoxicity will continue to remain a mystery in humans,
      if the underlying reaction is of idiosyncratic, unpredictable, and dose
      independent nature due potentially to some metabolic aberration in a few
      individuals emerging from kava use. In addition, kava hepatotoxicity is presently
      not reproducible experimentally in preclinical models, as demonstrated by studies
      showing whole kava extracts are not hepatotoxic. This led us to propose our
      'working hypothesis' that contaminant hepatotoxins including moulds might have
      caused rare kava hepatotoxicity in humans. Further studies are now warranted to
      proof or disproof our working hypothesis, because kava hepatotoxicity possibly
      based on contaminant hepatotoxins could be a preventable disease. In the
      meantime, however, for minimizing toxicity risk in kava users, a pragmatic
      approach should focus on the medicinal use of an aqueous extract derived from
      peeled rhizomes and roots of a non-mouldy noble kava cultivar, limited to maximum
      250-mg kavalactones daily for acute or intermittent use.

PMID- 22585546
TI  - In vivo O-Space imaging with a dedicated 12 cm Z2 insert coil on a human 3T
      scanner using phase map calibration.
AB  - Recently, spatial encoding with nonlinear magnetic fields has drawn attention for
      its potential to achieve faster gradient switching within safety limits, tailored
      resolution in regions of interest, and improved parallel imaging using encoding
      fields that complement the sensitivity profiles of radio frequency receive
      arrays. Proposed methods can broadly be divided into those that use phase
      encoding (Cartesian-trajectory PatLoc and COGNAC) and those that acquire
      nonlinear projections (O-Space, Null space imaging, radial PatLoc, and 4D-RIO).
      Nonlinear projection data are most often reconstructed with iterative algorithms
      that backproject data using the full encoding matrix. Just like conventional
      radial sequences that use linear spatial encoding magnetic fields, nonlinear
      projection methods are more sensitive than phase encoding methods to imperfect
      calibration of the encoding fields. In this work, voxel-wise phase evolution is
      mapped at each acquired point in an O-Space trajectory using a variant of
      chemical shift imaging, capturing all spin dynamics caused by encoding fields,
      eddy currents, and pulse timing. Phase map calibration is then applied to data
      acquired from a high-power, 12 cm, Z2 insert coil with an eight-channel radio
      frequency transmit-receive array on a 3T human scanner. We show the first
      experimental proof-of-concept O-Space images on in vivo and phantom samples,
      paving the way for more in-depth exploration of O-Space and similar imaging
      methods.

PMID- 22585549
TI  - CD4+ T-cell immunity after pandemic influenza vaccination cross-reacts with
      seasonal antigens and functionally differs from active influenza infection.
AB  - Antigen-specific antibodies are well characterized after vaccination with
      pandemic H1N1 or seasonal influenza vaccines. However, knowledge on cellular
      immunity toward pandemic H1N1 after vaccination and infection and cross
      reactivities toward seasonal antigens is limited. Nineteen individuals were
      vaccinated with the pandemic H1N1 vaccine. Among those, ten had been
      prevaccinated against seasonal influenza. CD4(+)  T cells specific for pandemic
      H1N1 and for seasonal vaccine, and antibodies were monitored using flow cytometry
      and ELISA/neutralization assays, respectively. In addition, seven patients with
      acute pandemic influenza infection were analyzed. Pandemic H1N1 vaccination
      induced a strong 4.63-fold (IQR 4.16) increase in antigen-specific CD4(+)  T
      cells that was more pronounced in individuals not prevaccinated with seasonal
      influenza (p = 0.01). T-cell levels toward seasonal vaccine concomitantly rose by
      2.71-fold (IQR 2.26). Likewise, prevaccination with seasonal influenza induced a
      less pronounced increase in specific antibodies. Influenza-specific T cells in
      vaccinees had a Th1 phenotype mainly coexpressing IFN-gamma and IL-2, whereas
      patients with active pandemic influenza showed a shift toward cells predominantly
      expressing IFN-gamma. In conclusion, T cells toward seasonal influenza antigens
      cross-react with pandemic H1N1 antigens and affect induction of specific T cells
      after pandemic influenza vaccination. In addition, the cytokine patterns of
      specific T cells during acute H1N1 infection and after vaccination differ, and
      the predominantly dual-positive cytokine profile of vaccine-induced T cells
      suggests sufficient functionality to confer successful virus control.

PMID- 22585550
TI  - Predicting the solid state phase diagram for glass-forming alloys of copper and
      zirconium.
AB  - The free energies of six crystal structures associated with Cu-Zr alloys-Cu (face
      centred cubic), Cu(2)Zr, Cu(10)Zr(7), CuZr, CuZr(2) and Zr (hexagonal close
      packed)-are calculated using the embedded atom potential of Mendelev et al (2009
      Phil. Mag. 89 967). We find that the observed low temperature stability of the
      Cu(10)Zr(7) and CuZr(2) phases is not reproduced. Instead, the model predicts
      that the CuZr phase remains stable down to T = 0 K. This discrepancy is largely
      removed when the interaction potentials are cut off at a short distance, such as
      that used by Duan et al (2005 Phys. Rev. B 71 224208). We present evidence,
      however, that the cut-off distance necessary to achieve the change in phase
      stability results in pathological artefacts in the energetics of some crystal
      phases.

PMID- 22585548
TI  - CD34-derived dendritic cells transfected ex vivo with HIV-Gag mRNA induce
      polyfunctional T-cell responses in nonhuman primates.
AB  - The pivotal role of DCs in initiating immune responses led to their use as
      vaccine vectors. However, the relationship between DC subsets involved in antigen
      presentation and the type of elicited immune responses underlined the need for
      the characterization of the DCs generated in vitro. The phenotypes of tissue
      derived APCs from a cynomolgus macaque model for human vaccine development were
      compared with ex vivo-derived DCs. Monocyte/macrophages predominated in bone
      marrow (BM) and blood. Myeloid DCs (mDCs) were present in all tested tissues and
      were more highly represented than plasmacytoid DCs (pDCs). As in human skin,
      Langerhans cells (LCs) resided exclusively in the macaque epidermis, expressing
      CD11c, high levels of CD1a and langerin (CD207). Most DC subsets were endowed
      with tissue-specific combinations of PRRs. DCs generated from CD34(+)  BM cells
      (CD34-DCs) were heterogeneous in phenotype. CD34-DCs shared properties
      (differentiation and PRR) of dermal and epidermal DCs. After injection into
      macaques, CD34-DCs expressing HIV-Gag induced Gag-specific CD4(+)  and CD8(+)  T
      cells producing IFN-gamma, TNF-alpha, MIP-1beta, or IL-2. In high responding
      animals, the numbers of polyfunctional CD8(+)  T cells increased with the number
      of booster injections. This DC-based vaccine strategy elicited immune responses
      relevant to the DC subsets generated in vitro.

PMID- 22585551
TI  - Understanding multimodal biological decisions from single cell and population
      dynamics.
AB  - Modern techniques on single-cell and -molecule resolution reveal that gene and
      protein expressions between cells of an otherwise identical group are stochastic
      in time, and clonal population of cells display heterogeneity in the abundance of
      a given protein per cell at any measured time. Today, combinatorially,
      stochasticity and heterogeneity are considered as biological noise and are
      essential for generating phenotypic variations, cell fate decisions and
      amplification of molecular signals. Here, several works from experimental and
      theoretical aspects that show multimodal biological decisions at single cell and
      population level are reviewed. The emerging lessons from these studies suggest
      that, for yielding multimodal decisions, living systems are guided by well
      defined nonlinear deterministic processes which are sensitive to specific range
      of biological parameters.

PMID- 22585552
TI  - [Results of flexor tendon sutures of the fingers with 2-strand (40 tendons) and 4
      strand (64 tendons) core sutures].
AB  - PURPOSE: This retrospective examination compares the results of finger flexor
      tendon sutures with 2 strands and 4 strands. It was checked, whether and how 2
      more strands influenced the rupture rate, the movement of the finger and the
      contentment of the patients. METHODS AND MATERIAL: From 1996 to 2000 for the core
      suture of the flexor tendon of fingers we used 2 strands. 35 patients with 40
      tendon sutures of 73 patients were examined. From 2001 to 2005 we used for the
      core suture 2 loop threads. 53 patients with 64 tendon sutures from a total of
      111 patients were examined. At least 12 months had passed between operation and
      the examination. The rupture rate and the range of movement of each finger joint
      and the total mobility of the affected fingers were evaluated. Each case was
      compared to the uninjured opposite hand. The functional result was judged
      according to the score of Buck-Gramcko. The patient's contentment was recorded by
      the DASH (disability of arm, shoulder and hand) score. Effects of gender, age,
      accompanying injuries, zone of the injury and their influence on the results were
      analysed. RESULTS: The Buck-Gramcko score showed in the 2-strand group a
      distribution from summarised 70% "excellent" and "good" and 30% "fair" and
      "poor". In the 4-strand-group the relation was 93.7% "excellent" and "good", 6.3%
      "fair", one "poor". In the 2-strand group 2/40 (5%) of the tendon sutures
      ruptured, in the 4-strand group 1/64 (1.6%) ruptured. The average DASH value in
      the 2-strands-group was 16.6/100, in the 4-strands-group 18.1/100 when 0 is the
      best possible result and 100 the worst. The patient judgement in the 2-strand
      group was summarised to 70% for "excellent" and "good" and 30% "fair" and "poor".
      In the 4-strand group the patient's judgment was summarised in 75% "excellent"
      and "good" and in 25% "fair". CONCLUSION: The results of flexor tendon sutures
      with 4-strand core sutures have been superior to the results with 2-strand core
      suture according to range of motion of the fingers (P <0.005).

PMID- 22585553
TI  - A rasopathy phenotype with severe congenital hypertrophic obstructive
      cardiomyopathy associated with a PTPN11 mutation and a novel variant in SOS1.
AB  - The RAS-MAPK pathway is critical for human growth and development. Abnormalities
      at different steps of this signaling cascade result in neuro-cardio-facial
      cutaneous syndromes, or the RASopathies, a group of disorders with overlapping
      yet distinct phenotypes. RASopathy patients have variable degrees of intellectual
      disability, poor growth, relative macrocephaly, ectodermal abnormalities,
      dysmorphic features, and increased risk for certain malignancies. Congenital
      heart disease, particularly hypertrophic cardiomyopathy (HCM) and pulmonic
      stenosis, are prominent features in these disorders. Significant locus
      heterogeneity exists for many of the RASopathies. Traditionally, these diseases
      were thought to be inherited in an autosomal dominant manner. However, recently
      patients with defects in two components of this pathway and overlapping features
      of various forms of Noonan syndrome and neurofibromatosis 1 and have been
      reported. Here we present a patient with severe, progressive neonatal HCM,
      elevated urinary catecholamine metabolites, and dysmorphic features in whom we
      identified a known LEOPARD syndrome-associated PTPN11 mutation (c.1403 C > T;
      p.T468M) and a novel, potentially pathogenic missense SOS1 variant (c.1018 C > T;
      p.P340S) replacing a rigid nonpolar imino acid with a polar amino acid at a
      highly conserved position. We describe detailed clinical manifestations, cardiac
      histopathology, and the molecular genetic findings. Oligogenic models of
      inheritance with potential synergistic effects should be considered in the
      RASopathies.

PMID- 22585554
TI  - Real-time correction by optical tracking with integrated geometric distortion
      correction for reducing motion artifacts in functional MRI.
AB  - Head motion artifacts are a major problem in functional MRI that limit its use in
      neuroscience research and clinical settings. Real-time scan-plane correction by
      optical tracking has been shown to correct slice misalignment and nonlinear spin
      history artifacts; however, residual artifacts due to dynamic magnetic field
      nonuniformity may remain in the data. A recently developed correction technique,
      Phase Labeling for Additional Coordinate Encoding, can correct for absolute
      geometric distortion using only the complex image data from two echo planar
      images with slightly shifted k-space trajectories. An approach is presented that
      integrates Phase Labeling for Additional Coordinate Encoding into a real-time
      scan-plane update system by optical tracking, applied to a tissue-equivalent
      phantom undergoing complex motion and an functional MRI finger tapping experiment
      with overt head motion to induce dynamic field nonuniformity. Experiments suggest
      that such integrated volume-by-volume corrections are very effective at artifact
      suppression, with potential to expand functional MRI applications.

PMID- 22585555
TI  - Polymethoxyflavonoids tangeretin and nobiletin increase glucose uptake in murine
      adipocytes.
AB  - Tangeretin and nobiletin are polymethoxyflavonoids that are contained in citrus
      fruits. Polymethoxyflavonoids are reported to have several biological functions
      including anti-inflammatory, anti-atherogenic, or anti-diabetic effects. However,
      whether polymethoxyflavonoids directly affect glucose uptake in tissues is not
      well understood. In the current study, we investigated whether tangeretin and
      nobiletin affect glucose uptake in insulin target cells such as adipocytes. We
      observed that treatment with tangeretin or nobiletin significantly increased the
      uptake of [(3) H]-deoxyglucose in differentiated 3T3-F442A adipocytes in a
      concentration-dependent manner. Data showed that phosphatidyl inositol 3 kinase,
      Akt1/2, and the protein kinase A pathways were involved in the increase in
      glucose uptake induced by polymethoxyflavonoids. These data suggest that the anti
      diabetic action of polymethoxyflavonoids is partly exerted via these signaling
      pathways in insulin target tissues.

PMID- 22585556
TI  - Identification of a regulatory subunit of protein phosphatase 1 which mediates
      blue light signaling for stomatal opening.
AB  - Protein phosphatase 1 (PP1) is a eukaryotic serine/threonine protein phosphatase
      comprised of a catalytic subunit (PP1c) and a regulatory subunit that modulates
      catalytic activity, subcellular localization and substrate specificity. PP1c
      positively regulates stomatal opening through blue light signaling between
      phototropins and the plasma membrane H(+)-ATPase in guard cells. However, the
      regulatory subunit functioning in this process is unknown. We identified
      Arabidopsis PRSL1 (PP1 regulatory subunit2-like protein1) as a regulatory subunit
      of PP1c. Tautomycin, a selective inhibitor of PP1c, inhibited blue light
      responses of stomata in the single mutants phot1 and phot2, supporting the idea
      that signals from phot1 and phot2 converge on PP1c. We obtained PRSL1 based on
      the sequence similarity to Vicia faba PRS2, a PP1c-binding protein isolated by a
      yeast two-hybrid screen. PRSL1 bound to Arabidopsis PP1c through its RVxF motif,
      a consensus PP1c-binding sequence. Arabidopsis prsl1 mutants were impaired in
      blue light-dependent stomatal opening, H(+) pumping and phosphorylation of the
      H(+)-ATPase, but showed normal phototropin activities. PRSL1 complemented the
      prsl1 phenotype, but not if the protein carried a mutation in the RVxF motif,
      suggesting that PRSL1 functions through binding PP1c via the RVxF motif. PRSL1
      did not affect the catalytic activity of Arabidopsis PP1c but it stimulated the
      localization of PP1c in the cytoplasm. We conclude that PRSL1 functions as a
      regulatory subunit of PP1 and regulates blue light signaling in stomata.

PMID- 22585557
TI  - A double burden: emotional eating and lack of cognitive reappraisal in eating
      disordered women.
AB  - OBJECTIVE: To examine the influence of emotional eating and lack of cognitive
      reappraisal on eating pathology in women with binge-purge and restricting type
      eating disorders. METHOD: Women with a diagnosis of anorexia or bulimia nervosa
      according to the DSM-IV-tr (n = 50) and non-clinical women without eating
      disorders (n = 52) were asked about emotional eating tendencies, adaptive emotion
      regulation strategies (cognitive reappraisal) and eating pathology symptoms.
      RESULTS: In binge-purging women, emotional eating with limited use of cognitive
      reappraisal predicted level of eating pathology but not in the restricting and
      non-clinical women. DISCUSSION: Emotional eating tendencies in combination with a
      low tendency to use cognitive reappraisal may influence the severity of eating
      pathology in individuals with binge-purge behaviours. Evidently, patients with
      these characteristics require a therapy that addresses adaptive emotion
      regulation skills.

PMID- 22585558
TI  - Sensitivity of prestaining RNA with ethidium bromide before electrophoresis and
      performance of subsequent northern blots using heterologous DNA probes.
AB  - Adding ethidium bromide (EtBr) at low concentrations to RNA samples before
      running formaldehyde-agarose gels affords the advantages of checking RNA
      integrity and evaluating the quality of size-separation at any time during
      electrophoresis or immediately after either electrophoresis or blotted the
      separated RNA onto the membrane without significantly compromising mobility,
      transfer, or hybridization. In this study, we systematically examined the factors
      that affect the sensitivity of RNA prestaining by heating RNA samples that
      include EtBr before electrophoresis under different denaturation conditions. We
      also examined the efficiency of the hybridization of EtBr-prestained RNA with
      heterologous DNA probes. The results showed that the fluorescent intensity of
      EtBr-prestained RNA was affected not only by the EtBr concentration as previously
      reported but also by the RNA amount, denaturation time, and denaturation
      temperature. Prior staining of RNA with 40 MUg/mL EtBr significantly decreased
      the efficiency of Northern blot hybridization with heterologous DNA probes. We
      propose that to best combine staining sensitivity and the efficiency of Northern
      blot hybridization with heterologous DNA probes, the concentration of EtBr used
      to prestain RNA should not exceed 30 MUg/mL. The efficiency of the hybridization
      of EtBr-prestained RNA was affected not only by factors that affect staining
      sensitivity but also by the type of probe used.

PMID- 22585559
TI  - Pseudoaneurysm of the genicular artery after wound closure using a skin stapler
      in a child.
AB  - A 9-year-old child with a left humerus fracture also had minor skin cuts on the
      right knee, which were closed with a skin stapler. After 1 week, a medial
      superior genicular artery pseudoaneurysm developed, which was treated by
      ultrasound-guided compression. This case illustrates a unique complication of the
      use of a skin stapler device.

PMID- 22585560
TI  - Anti-inflammatory effects of high-dose IgG on TNF-alpha-activated human coronary
      artery endothelial cells.
AB  - High-dose infusion of IgG (IVIG) is used to treat autoimmune and inflammatory
      diseases, including Kawasaki disease (KD). Although the immunomodulatory effects
      of IVIG on blood cells such as macrophages have been well studied, its effects on
      tissue cells remain unclear. Here, we show that high-dose IgG specifically and
      completely inhibited TNF-alpha-induced, but not IL-1beta-induced, secretion of
      proinflammatory cytokines such as G-CSF and IL-6 by cultured human coronary
      artery endothelial cells (HCAECs). High-dose IgG did not inhibit TNF-alpha
      mediated early signaling events of the NF-kappaB and MAPK pathways but it
      potently inhibited gene expression of G-CSF and IL-6 12 h after TNF-alpha
      stimulation. Interestingly, suppression of the G-CSF and IL-6 gene expression
      correlated closely with functional inhibition of a transcription factor,
      C/EBPdelta, whose binding sites in the promoters of G-CSF and IL-6 have been
      shown to be critical for their transcriptional activation. Furthermore, the
      inhibitory effect of intact IgG on HCAECs was exerted mainly via its F(ab')(2) 
      fragment, and not its Fc fragment. These findings suggest that the clinical
      effects of IVIG on KD patients are at least in part due to its direct anti
      inflammatory effects on the coronary endothelium, which is a major lesion site in
      the pathogenesis of KD.

PMID- 22585561
TI  - Resveratrol protects cortical neurons against microglia-mediated
      neuroinflammation.
AB  - Neuroinflammation is closely associated with the pathogenesis of neurological
      disorders. The hallmark of neuroinflammation is considered to be microglial
      activation. Therefore, inhibition of microglial activation might hold a promising
      therapy for neurological disorders. Resveratrol, a natural non-flavonoid
      polyphenol found in grapes and red wine, has been recognized as a bioactive agent
      with potential benefit for health. Several lines of evidence show that
      resveratrol could exert neuroprotection against ischemia, seizure, and
      neurodegenerative diseases. However, the mechanisms underlying its beneficial
      neuroprotective effects are poorly defined. Here, by using rat primary cortical
      neuron-glia cultures, results showed that resveratrol attenuated
      lipopolysaccharide (LPS)-induced cortical neurotoxicity. Further studies revealed
      that microglia were responsible for resveratrol-mediated neuroprotection.
      Resveratrol significantly inhibited LPS-induced microglial activation and
      subsequent production of multiple pro-inflammatory and cytotoxic factors such as
      tumor necrosis factor-alpha, nitric oxide, and interleukin-1beta. Collectively,
      resveratrol produced neuroprotection against microglia-induced neurotoxicity.
      Thus, resveratrol might represent a potential benefit for the treatment of
      inflammation-related neurological disorders.

PMID- 22585562
TI  - Phenotypic and functional characteristics of CD4+ CD39+ FOXP3+ and CD4+ CD39+
      FOXP3neg T-cell subsets in cancer patients.
AB  - Human CD4(+) CD39(+)  regulatory T (Treg) cells hydrolyze exogenous adenosine
      triphosphate (ATP) and participate in immunosuppressive adenosine production.
      They contain two T-cell subsets whose role in mediating suppression is not
      understood. Frequencies of both CD4(+) CD39(+)  subsets were evaluated in
      peripheral blood lymphocytes of 57 cancer patients and in tumor infiltrating
      lymphocytes (TILs) of 6 patients. CD4(+) CD39(+)  and CD4(+) CD39(neg)  T cells
      isolated using immunobeads and cell sorting were cultured under various
      conditions. Their conversion into CD39(+) FOXP3(+) CD25(+)  or CD39(+) FOX(neg)
      CD25(neg)  cells was monitored by multiparameter flow cytometry. Hydrolysis of
      exogenous ATP was measured in luminescence assays. Two CD4(+) CD39(+)  cell
      subsets differing in expression of CD25, FOXP3, CTLA-4, CD121a, PD-1, latency
      associated peptide (LAP), glycoprotein A repetitions predominant (GARP), and the
      cytokine profile accumulated with equal frequencies in the blood and tumor
      tissues of cancer patients. The frequency of both subsets was significantly
      increased in cancer. CD39 expression levels correlated with the subsets' ability
      to hydrolyze ATP. Conventional CD4(+) CD39(neg)  T cells incubated with IL-2 +
      TGF-beta expanded to generate CD4(+) CD39(+) FOXP3(+)  Treg cells, while CD4(+)
      CD39(+) FOXP3(neg) CD25(neg)  subset cells stimulated via the TCR and IL-2
      converted to FOXP3(+) CTLA4(+) CD25(+)  TGF-beta-expressing Treg cells. Among
      CD4(+) CD39(+)  Treg cells, the CD4(+) CD39(+) FOXP3(neg) CD25(neg)  subset
      serves as a reservoir of cells able to convert to Treg cells upon activation by
      environmental signals.

PMID- 22585563
TI  - Core needle biopsy of spinal lesions under CT guidance: review of 79 cases.
AB  - The authors report the results of a retrospective study about computed tomography
      (CT)-guided percutaneous vertebral biopsies in 79 cases (44 males and 35 females,
      aged from 6 to 84 years old). Five biopsies were performed at the cervical level,
      31 at the thoracic, 30 at the lumbar, and 13 at the sacrum. A diagnosis was
      obtained in 75 out of the 79 patients. Diagnostic yield was 95%, and diagnostic
      accuracy was 97.3%. Core needle biopsy under CT guidance for spinal lesions is a
      fast, relatively simple, minimally invasive, and low-cost method, with high
      levels of diagnostic accuracy and few complications. It plays a major role in the
      correct diagnosis and therapeutic planning. CT guidance allows safe and accurate
      biopsy of osseous lesions throughout the spine, obviating invasive open biopsy in
      most cases.

PMID- 22585564
TI  - Strategies in the treatment of distal cerebellar aneurysms: report of a series of
      11 patients.
AB  - BACKGROUND: Distal cerebellar artery aneurysms are rare entities and treatment
      modalities technically challenging. In recent years, new therapeutic options have
      emerged through microsurgical and endovascular means. OBJECTIVE: Based on a
      series of 11 cases, we describe combined interdisciplinary treatment strategies
      and report the outcome in a midterm follow-up interval of 12 months. METHODS:
      Collection of clinical case data during acute phase and follow-up including
      standardized angiographic control intervals during follow-up and assessment of
      the outcome. RESULTS: 7 of 11 reported cases had flow-related aneurysms based on
      an underlying arteriovenous malformation (AVM) or dural arteriovenous fistula
      (DAVF); we found multiple aneurysms in four cases. All patients with flow-related
      aneurysms presented with subarachnoid hemorrhage (SAH). Only one of four patients
      in this series without an underlying AVM or DAVF presented with SAH that was
      attributable to a distal cerebellar aneurysm. In one case, we observed a de novo
      formation of two flow-associated distal aneurysms (10 years interval). Two
      patients were treated conservatively, five patients were treated endovascularly,
      one patient was treated surgically and three patients were treated with combined
      methods. 9 of 11 patients with initial SAH had a good outcome. CONCLUSIONS:
      Distal cerebellar aneurysms associated with AVM or DAVF are rare but
      characterized by a high risk of hemorrhage. The present series indicates that an
      experienced interdisciplinary team and the combination of available techniques
      may lead to a reduction of complications and to a better outcome.

PMID- 22585565
TI  - Quality of life 1 year after aneurysmal subarachnoid hemorrhage in good outcome
      patients treated by clipping or coiling.
AB  - BACKGROUND AND PURPOSE: A study was conducted to compare the quality of life
      (QOL) of surgically versus endovascularly treated patients with ruptured cerebral
      aneurysms. METHODS: We treated 45 patients surgically (surgical clipping [SC]
      group) and 44 by endovascular therapy (coil embolization [CE] group). A
      standardized test of QOL and a structured interview were employed to assess
      changes 1 year after subarachnoid hemorrhage (SAH). One neurosurgical team using
      the same treatment protocols treated all patients. The SC and CE groups did not
      differ significantly in age, sex, education, aneurysm size, Hunt and Hess grade,
      Glasgow outcome scale (GOS) score, and intelligence quotient (IQ). RESULTS:
      Generally, the patients reported psychological changes (impairment in memory,
      47%; concentration, 20%; and ability to learn new things, 12%), which they
      subjectively related to SAH. On the one hand, 31% of the patients believed that
      close relatives noticed changes in their psychological condition as a result of
      the intervention. On the other hand, 61% reported an unaltered economic
      situation, 51% were well adjusted in work, and 70% claimed their family
      relationships remained unchanged. In comparison with the controls, patients
      claimed to have lower QOL in the areas of sexuality, love, psychic well-being,
      physical autonomy, and health. No differences in QOL were found between the SE
      and CE groups. CONCLUSIONS: The differences in QOL in the patients treated by
      either coiling or clipping were small and nonsignificant. Participants in both
      groups mentioned lower QOL in the areas of intimate relationships and health.

PMID- 22585566
TI  - Asymmetric polymicrogyria and periventricular nodular heterotopia due to mutation
      in ARX.
AB  - Mutations in the ARX gene, at Xp22.3, cause several disorders, including
      infantile spasms, X-linked lissencephaly with abnormal genitalia (XLAG), callosal
      agenesis and isolated intellectual disability. Genotype/phenotype studies
      suggested that polyalanine tract expansion is associated with non-malformative
      phenotypes, while missense and nonsense mutations cause cerebral malformations,
      however, patients with structural normal brain and missense mutations have been
      reported. We report on a male patient born with cleft lip and palate who
      presented with infantile spasms and hemiplegia. MRI showed agenesis of corpus
      callosum (ACC), an interhemispheric cyst, periventricular nodular heterotopia
      (PVNH), and extensive left frontal polymicrogyria (PMG). Sequencing of the ARX
      gene in the patient identified a six basepair insertion (c.335ins6, exon 2). The
      insertion leads to a two-residue expansion of the first polyalanine tract and was
      described previously in a family with non-syndromic X-linked mental retardation.
      To our knowledge, ARX mutation causing PMG and PVNH is unique, but the spasms and
      ACC are common in ARX mutations. Clinicians should be aware of the broad clinical
      range of ARX mutations, and further studies are necessary to investigate the
      association with PMG and PVNH and to identify possible modifying factors.

PMID- 22585568
TI  - Mesenteric carcinoid.

PMID- 22585567
TI  - 64-section multiphase CT enterography as a diagnostic tool in the evaluation of
      obscure gastrointestinal bleeding.
AB  - BACKGROUND AND AIM: Small bowel follow through (SBFT) and enteroclysis have low
      sensitivity in picking up lesions in obscure gastrointestinal bleed (OGIB).
      Computed tomographic enterography (CT-EG), performed with 64-slice multiphase CT
      system by using large volumes of ingested neutral enteric contrast material, has
      high spatial and temporal resolution in visualization of the small bowel wall and
      lumen. The role of 64-slice multiphase CT-EG in the evaluation of OGIB is still
      evolving, and data on this role are scarce. We evaluated the efficacy of 64-slice
      multiphase CT-EG using polyethylene glycol (PEG) electrolyte solution as neutral
      contrast in patients of OGIB. METHODS: CT-EG was performed with 64-slice
      multiphase CT system using large volume (2,000 mL) of PEG electrolyte solution as
      oral contrast in patients of OGIB. RESULTS: Thirty-five patients (21 men, age
      41.4 [13.5] y, range 19-70 year) with OGIB underwent CT-EG; 20 patients had overt
      OGIB whereas 15 patients had occult OGIB. Among 15 patients with occult OGIB, 10
      patients had iron deficiency anemia (IDA) with fecal occult blood test (FOBT)
      positive and 5 had IDA with FOBT negative. Thirty-two patients (92 %) completed
      the procedure successfully. The total time taken for the ingestion of 2,000 mL of
      PEG electrolyte solution was median 64 (range 60-78) minutes. Adequate luminal
      distension of small bowel was seen in 29 (90.6 %) patients for successful
      interpretation of radiological images. Fifteen of 32 (46.9 %) patients had
      positive findings on CT-EG; 12 of them underwent exploratory laparotomy. The
      surgical findings were in conformity with CT-EG findings in all patients, which
      included gastrointestinal stromal tumors (GIST; n = 6), carcinoid (1), Meckel's
      diverticulum (1), small bowel adenocarcinoma (2) and jejunal vascular
      malformation (2). CONCLUSION: 64-slice multiphase CT-EG is a useful investigation
      in the evaluation of both occult and overt OGIB.

PMID- 22585569
TI  - An unusual endoscopic presentation of solitary rectal ulcer syndrome.
AB  - Solitary rectal ulcer syndrome (SRUS) is an uncommon rectal disorder. Massive
      rectal bleeding is a rare presentation of SRUS, and can pose an endoscopic
      challenge in differentiating from other causes of massive rectal bleeding. A 22
      year-old man presented with massive rectal bleeding which had SRUS with spurting
      bleeding on lower endoscopic evaluation. He was treated by endoscopic hemostasis
      using argon plasma coagulation. He had no complaint after a month and follow up
      lower endoscopy proved complete healing within two months. SRUS should be
      considered as a potential cause of massive rectal bleeding.

PMID- 22585570
TI  - Implementation of vascular-space-occupancy MRI at 7T.
AB  - Vascular-space-occupancy (VASO) MRI exploits the difference between blood and
      tissue T1 to null blood signal and measure cerebral blood volume changes using
      the residual tissue signal. VASO imaging is more difficult at higher field
      because of sensitivity loss due to the convergence of tissue and blood T1 values
      and increased contamination from blood-oxygenation-level-dependent (BOLD)
      effects. In addition, compared to 3T, 7T MRI suffers from increased geometrical
      distortions, e.g., when using echo-planar-imaging, and from increased power
      deposition, the latter especially problematic for the spin-echo-train sequences
      commonly used for VASO MRI. Third, non-steady-state blood spin effects become
      substantial at 7T when only a head coil is available for radiofrequency transmit.
      In this study, the magnetization-transfer-enhanced-VASO approach was applied to
      maximize tissue-blood signal difference, which boosted signal-to-noise ratio by
      149% +/- 13% (n = 7) compared to VASO. Second, a 3D fast gradient-echo sequence
      with low flip-angle (7 degrees ) and short echo-time (1.8 ms) was used to
      minimize the BOLD effect and to reduce image distortion and power deposition.
      Finally, a magnetization-reset technique was combined with a motion-sensitized
      driven-equilibrium approach to suppress three types of non-steady-state spins.
      Our initial functional MRI results in normal human brains at 7T with this
      optimized VASO sequence showed better signal-to-noise ratio than at 3T.

PMID- 22585571
TI  - Glucocorticoid receptor dimerization induces MKP1 to protect against TNF-induced
      inflammation.
AB  - Glucocorticoids acting through the glucocorticoid receptor (GR) inhibit TNF
      induced lethal inflammation. Here, we demonstrate that GR dimerization plays a
      role in reducing TNF sensitivity. In mutant mice unable to dimerize GR, we found
      that TNF failed to induce MAPK phosphatase 1 (MKP1). We assessed TNF sensitivity
      in Mkp1(-/-) mice and found increased inflammatory gene induction in livers,
      increased circulating cytokines, cell death in intestinal epithelium, severe
      intestinal inflammation, hypothermia, and death. Mkp1(-/-) mice had increased
      levels of phosphorylated JNK, which promotes apoptosis, in liver tissue. We
      further examined JNK-deficient mice for their response to TNF. Although Jnk1(-/-)
      mice showed no change in sensitivity to TNF, Jnk2(-/-) mice were significantly
      protected against TNF, identifying JNK2 as an essential player in inflammation
      induced by TNF. Furthermore, we found that loss of Jnk2 partially rescued the
      increased sensitivity of Mkp1(-/-) and mutant GR mice to TNF. Our data show that
      GR dimerization inhibits JNK2 through MKP1 and protects from TNF-induced
      apoptosis and lethal inflammation.

PMID- 22585572
TI  - Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal.
AB  - Glyoxalase 1 (Glo1) expression has previously been associated with anxiety in
      mice; however, its role in anxiety is controversial, and the underlying mechanism
      is unknown. Here, we demonstrate that GLO1 increases anxiety by reducing levels
      of methylglyoxal (MG), a GABAA receptor agonist. Mice overexpressing Glo1 on a Tg
      bacterial artificial chromosome displayed increased anxiety-like behavior and
      reduced brain MG concentrations. Treatment with low doses of MG reduced anxiety
      like behavior, while higher doses caused locomotor depression, ataxia, and
      hypothermia, which are characteristic effects of GABAA receptor activation.
      Consistent with these data, we found that physiological concentrations of MG
      selectively activated GABAA receptors in primary neurons. These data indicate
      that GLO1 increases anxiety by reducing levels of MG, thereby decreasing GABAA
      receptor activation. More broadly, our findings potentially link metabolic state,
      neuronal inhibitory tone, and behavior. Finally, we demonstrated that
      pharmacological inhibition of GLO1 reduced anxiety, suggesting that GLO1 is a
      possible target for the treatment of anxiety disorders.

PMID- 22585573
TI  - Antigen-presenting cell-derived complement modulates graft-versus-host disease.
AB  - Acute graft-versus-host disease (GvHD) is a serious complication of allogeneic
      hematopoietic cell transplantation (allo-HCT) that results from donor allogeneic
      T cell attack on host tissues. Based on previous work implicating immune cell
      derived C3a and C5a as regulators of T cell immunity, we examined the effects of
      locally produced C3a and C5a on murine T cell-mediated GvHD. We found that total
      body irradiation, a conditioning regimen required to permit engraftment of allo
      HCT, caused upregulation and activation of alternative pathway complement
      components by recipient APCs. Allo-HCT with decay accelerating factor-null (Daf1(
      /-)) host BM and Daf1(-/-) donor lymphocytes led to exacerbated GvHD outcome and
      resulted in splenic and organ-infiltrating T cell expansion. T cells deficient in
      C3a receptor (C3aR) and/or C5a receptor (C5aR) responded weakly in allogeneic
      hosts and exhibited limited ability to induce GvHD. Using a clinically relevant
      treatment strategy, we showed that pharmacological C5aR blockade reduced GvHD
      morbidity. Our data mechanistically link APC-derived complement to T cell
      mediated GvHD and support complement inhibition as a therapeutic strategy for
      GvHD in humans.

PMID- 22585574
TI  - p38 Inhibition ameliorates skin and skull abnormalities in Fgfr2 Beare-Stevenson
      mice.
AB  - Beare-Stevenson cutis gyrata syndrome (BSS) is a human genetic disorder
      characterized by skin and skull abnormalities. BSS is caused by mutations in the
      FGF receptor 2 (FGFR2), but the molecular mechanisms that induce skin and skull
      abnormalities are unclear. We developed a mouse model of BSS harboring a FGFR2
      Y394C mutation and identified p38 MAPK as an important signaling pathway
      mediating these abnormalities. Fgfr2+/Y394C mice exhibited epidermal hyperplasia
      and premature closure of cranial sutures (craniosynostosis) due to abnormal cell
      proliferation and differentiation. We found ligand-independent phosphorylation of
      FGFR2 and activation of p38 signaling in mutant skin and calvarial tissues.
      Treating Fgfr2+/Y394C mice with a p38 kinase inhibitor attenuated skin
      abnormalities by reversing cell proliferation and differentiation to near normal
      levels. This study reveals the pleiotropic effects of the FGFR2 Y394C mutation
      evidenced by cutis gyrata, acanthosis nigricans, and craniosynostosis and
      provides a useful model for investigating the molecular mechanisms of skin and
      skull development. The demonstration of a pathogenic role for p38 activation may
      lead to the development of therapeutic strategies for BSS and related conditions,
      such as acanthosis nigricans or craniosynostosis.

PMID- 22585575
TI  - CHK1 targets spleen tyrosine kinase (L) for proteolysis in hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies
      resistant to current chemotherapies or radiotherapies, which makes it urgent to
      identify new therapeutic targets for HCC. In this study, we found that checkpoint
      kinase 1 (CHK1) was frequently overexpressed and correlated with poor clinical
      outcome in patients with HCC. We further showed that the CHK1 inhibitor GO6976
      was capable of sensitizing HCC cells to cisplatin, indicating that CHK1 may have
      oncogenic function in HCC. We found that CHK1 phosphorylated the tumor suppressor
      spleen tyrosine kinase (L) (SYK[L]) and identified the phosphorylation site at
      Ser295. Furthermore, CHK1 phosphorylation of SYK(L) promoted its subsequent
      proteasomal degradation. Expression of a nonphosphorylated mutant of SYK(L) was
      more efficient at suppressing proliferation, colony formation, mobility, and
      tumor growth in HCC lines. Importantly, a strong inverse correlation between the
      expression levels of CHK1 and SYK(L) was observed in patients with HCC.
      Collectively, our data demonstrate that SYK(L) is a substrate of CHK1 in tumor
      cells and suggest that targeting the CHK1/SYK(L) pathway may be a promising
      strategy for treating HCC.

PMID- 22585576
TI  - Angiopoietin-2 differentially regulates angiogenesis through TIE2 and integrin
      signaling.
AB  - Angiopoietin-2 (ANG-2) is a key regulator of angiogenesis that exerts context
      dependent effects on ECs. ANG-2 binds the endothelial-specific receptor tyrosine
      kinase 2 (TIE2) and acts as a negative regulator of ANG-1/TIE2 signaling during
      angiogenesis, thereby controlling the responsiveness of ECs to exogenous
      cytokines. Recent data from tumors indicate that under certain conditions ANG-2
      can also promote angiogenesis. However, the molecular mechanisms of dual ANG-2
      functions are poorly understood. Here, we identify a model for the opposing roles
      of ANG-2 in angiogenesis. We found that angiogenesis-activated endothelium
      harbored a subpopulation of TIE2-negative ECs (TIE2lo). TIE2 expression was
      downregulated in angiogenic ECs, which abundantly expressed several integrins.
      ANG-2 bound to these integrins in TIE2lo ECs, subsequently inducing, in a TIE2
      independent manner, phosphorylation of the integrin adaptor protein FAK,
      resulting in RAC1 activation, migration, and sprouting angiogenesis.
      Correspondingly, in vivo ANG-2 blockade interfered with integrin signaling and
      inhibited FAK phosphorylation and sprouting angiogenesis of TIE2lo ECs. These
      data establish a contextual model whereby differential TIE2 and integrin
      expression, binding, and activation control the role of ANG-2 in angiogenesis.
      The results of this study have immediate translational implications for the
      therapeutic exploitation of angiopoietin signaling.

PMID- 22585577
TI  - Ganglioside GD2 identifies breast cancer stem cells and promotes tumorigenesis.
AB  - Cancer stem cells (CSCs) are a small subpopulation of cancer cells that have
      increased resistance to conventional therapies and are capable of establishing
      metastasis. However, only a few biomarkers of CSCs have been identified. Here, we
      report that ganglioside GD2 (a glycosphingolipid) identifies a small fraction of
      cells in human breast cancer cell lines and patient samples that are capable of
      forming mammospheres and initiating tumors with as few as 10 GD2+ cells. In
      addition, the majority of GD2+ cells are also CD44hiCD24lo, the previously
      established CSC-associated cell surface phenotype. Gene expression analysis
      revealed that GD3 synthase (GD3S) is highly expressed in GD2+ as well as in
      CD44hiCD24lo cells and that interference with GD3S expression, either by shRNA or
      using a pharmacological inhibitor, reduced the CSC population and CSC-associated
      properties. GD3S knockdown completely abrogated tumor formation in vivo. Also,
      induction of epithelial-mesenchymal transition (EMT) in transformed human mammary
      epithelial cells (HMLER cells) dramatically increased GD2 as well as GD3S
      expression in these cells, suggesting a role of EMT in the origin of GD2+ breast
      CSCs. In summary, we identified GD2 as a new CSC-specific cell surface marker and
      GD3S as a potential therapeutic target for CSCs, with the possibility of
      improving survival and cure rates in patients with breast cancer.

PMID- 22585578
TI  - Comorbidity and disease burden in the National Comorbidity Survey Replication
      (NCS-R).
AB  - BACKGROUND: Disease burden estimates rarely consider comorbidity. Using a
      recently developed methodology for integrating information about comorbidity into
      disease burden estimates, we examined the comparative burdens of nine mental and
      10 chronic physical disorders in the National Comorbidity Survey Replication (NCS
      R). METHODS: Face-to-face interviews in a national household sample (n = 5,692)
      assessed associations of disorders with scores on a visual analog scale (VAS) of
      perceived health. Multiple regression analysis with interactions for comorbidity
      was used to estimate these associations. Simulation was used to estimate
      incremental disorder-specific effects adjusting for comorbidity. RESULTS: The
      majority of respondents (74.9%) reported one or more disorders. Of respondents
      with disorders, 73.8-98.2% reported having at least one other disorder. The best
      fitting model to predict VAS scores included disorder main effects and
      interactions for number of disorders. Adjustment for comorbidity reduced
      individual-level disorder-specific burden estimates substantially, but with
      considerable between-disorder variation (0.07-0.69 ratios of disorder-specific
      estimates with and without adjustment for comorbidity). Four of the five most
      burdensome disorders at the individual level were mental disorders based on
      bivariate analyses (panic/agoraphobia, bipolar disorder, posttraumatic stress
      disorder, major depression) but only two based on multivariate analyses,
      adjusting for comorbidity (panic/agoraphobia, major depression). Neurological
      disorders, chronic pain conditions, and diabetes were the other most burdensome
      individual-level disorders. Chronic pain conditions, cardiovascular disorders,
      arthritis, insomnia, and major depression were the most burdensome societal-level
      disorders. CONCLUSIONS: Adjustments for comorbidity substantially influence
      estimates of disease burden, especially those of mental disorders, underlining
      the importance of including information about comorbidity in studies of mental
      disorders.

PMID- 22585579
TI  - Relationship between body mass index, fat distribution and cardiometabolic risk
      factors in Indian children and adolescents.
AB  - BACKGROUND: Studies assessing the relationship of BMI and BF with cardiometabolic
      (CM) risks in Indian children are scarce. OBJECTIVE: To assess the occurrence of
      cardiometabolic risk factors in Indian children and adolescents in relation to
      BMI and body fat and to study their association with body fat distribution.
      METHODS: 286 children and adolescents (mean age 11.2 +/- 2.6 years, 139 boys)
      were recruited from routine health checks and schools. Anthropometry and blood
      pressure were recorded, total body fat (BF) and fat distribution (android and
      gynoid) were measured by Dual Energy X-ray Absorptiometry. Fasting plasma
      glucose, lipid profile and insulin were also measured. RESULTS: When the study
      cohort was divided as per their BMI and biochemical cardiometabolic risk factors,
      8% children had normal BMI with abnormal biochemical parameters while 40%
      children had abnormal BMI but normal biochemical parameters. CONCLUSION: There
      are normal weight children with cardiometabolic risks. There was an increase in
      the occurrence of cardiometabolic risk factors with increased android
      distribution of fat (p-value < 0.05).

PMID- 22585580
TI  - Thymocyte death by neglect: contribution of engulfing macrophages.
AB  - The thymus provides the microenvironment in which thymocytes develop into mature
      T cells, and interactions with thymic stromal cells are thought to provide the
      necessary signals for thymocyte maturation. Recognition of self-MHC by T cells is
      a basic requirement for mature T-cell functions, and those thymocytes that do not
      recognize the peptide-loaded self-MHC molecules found in the thymus, and
      therefore lack a TCR signal, undergo a default death pathway named "death by
      neglect" in the thymic cortex. In the absence of this TCR signaling, it has been
      suggested that binding of glucocorticoids to - or the ligation of certain cell
      surface molecules, such as CD8, CD24, CD45, or CD99 on - these neglected
      thymocytes will induce them to enter the apoptotic program. Apoptotic thymocytes
      are cleared by the surrounding macrophages and, as a consequence, these
      macrophages are known to release various molecules, such as adenosine, retinoids,
      TGF-beta, ATP, and carbon monoxide. Interestingly, all these molecules have been
      described to induce or promote apoptosis in thymocytes in the absence of TCR
      signaling. Here, we propose that thymic macrophages, because they continually
      engulf apoptotic cells, might constantly provide these cell death-inducing
      signals, and thus contribute to the formation of a thymic milieu that ensures the
      effective induction of "death by neglect".

PMID- 22585581
TI  - The need for updates of spin system parameters, illustrated for the case of gamma
      aminobutyric acid.

PMID- 22585582
TI  - [Prevalence of affective and anxiety disorders in cancer: systematic literature
      review and meta-analysis].
AB  - We aimed to systematically summarize the empirical evidence on the 4-week-, 12
      month-, and lifetime prevalence of affective and anxiety disorders in cancer
      patients. We evaluated 89 English or German language original papers and
      systematic reviews that assessed the prevalence of affective and anxiety
      disorders using structured clinical interviews published between 1995 and 2010.
      Adjusted prevalence rates were calculated using a random-intercept model. The
      pooled adjusted 4-week prevalence of affective disorders was 11.1% (95% CI 8.1
      15.1), and 10.8% (95% CI 6.8-16.7) based on German studies. The pooled adjusted 4
      week prevalence of anxiety disorders was 10.2% (95% CI 6.9-14.8), and 13.5% (95%
      CI 7.1-24.3) based on German studies. The findings show the need for further
      research on representative studies that take into account the range of
      psychosocial stressors and supportive care needs in addition to the prevalence of
      mental disorders.

PMID- 22585583
TI  - [Physical and mental long-term sequelae following intensive care of severe sepsis
      in patients and relatives].
AB  - This study aimed at investigating the physical and mental long-term sequelae in
      survivors of severe sepsis and in their relatives. Furthermore, the role of
      resilience as protective factor was examined. We contacted all persons who had
      requested free of charge advice from the German Sepsis Aid's National Helpline
      and asked them to answer a questionnaire. We included 87 patients and 90
      relatives of patients who survived a severe sepsis. About two thirds of the
      patients and relatives reported clinically relevant post-traumatic symptoms.
      There were strong dyadic relations between patient and spouses regarding physical
      and mental health and quality of life. Resilience was found to be a significant
      negative predictor of physical complaints, anxiety, depression and post-traumatic
      stress symptoms in patients and relatives. Diagnosis and therapy of mental
      disorders is of particular importance within primary care following sepsis.

PMID- 22585584
TI  - [Menopausal complaints across the lifespan? Findings of a German representative
      survey].
AB  - Aim of the present investigation was the assessment of magnitude and distribution
      of subjective menopausal complaints in the German population. Study participants
      included 1 350 women aged 14-92 years, completing the menopause rating scale (MRS
      II). A total of 22% of the women exhibited considerable/severe menopausal
      complaints. Symptoms as sleep problems, joint and muscular discomfort, heart
      discomfort and physical and mental exhaustion increased drastically with
      advancing age. Hot flushes/sweating were the only symptoms specifically assigned
      to the menopausal period. Significant predictors for the intensity of menopausal
      complaints were: region of living, age, level of psychic burden, somatic
      complaints, depression, stress and fatigue. It is concluded that menopausal
      symptoms referred to in the literature must be questioned to be phase specific.
      Further research on aetiological factors is needed.

PMID- 22585586
TI  - The idic(15) syndrome: expanding the phenotype.

PMID- 22585585
TI  - Freeze-thaw lysates of Plasmodium falciparum-infected red blood cells induce
      differentiation of functionally competent regulatory T cells from memory T cells.
AB  - In addition to naturally occurring regulatory T (nTreg) cells derived from the
      thymus, functionally competent Treg cells can be induced in vitro from peripheral
      blood lymphocytes in response to TCR stimulation with cytokine costimulation.
      Using these artificial stimulation conditions, both naive as well as memory
      CD4(+)  T cells can be converted into induced Treg (iTreg) cells, but the
      cellular origin of such iTreg cells in vivo or in response to more physiologic
      stimulation with pathogen-derived antigens is less clear. Here, we demonstrate
      that a freeze/thaw lysate of Plasmodium falciparum schizont extract (PfSE) can
      induce functionally competent Treg cells from peripheral lymphocytes in a time-
      and dose-dependent manner without the addition of exogenous costimulatory
      factors. The PfSE-mediated induction of Treg cells required the presence of nTreg
      cells in the starting culture. Further experiments mixing either memory or naive
      T cells with antigen presenting cells and CFSE-labeled Treg cells identified
      CD4(+) CD45RO(+) CD25(-)  memory T cells rather than Treg cells as the primary
      source of PfSE-induced Treg cells. Taken together, these data suggest that in the
      presence of nTreg cells, PfSE induces memory T cells to convert into iTreg cells
      that subsequently expand alongside PfSE-induced effector T cells.

PMID- 22585588
TI  - Diesel and biodiesels induce hepatic palmitoyl-CoA oxidase enzymatic activity
      through different molecular mechanisms in rats.
AB  - Induction of palmitoyl-CoA oxidase enzymatic activity in rat liver suggests that
      ingestion of diesel and biodiesels can cause mild hepatic peroxisomal
      proliferation. Surprisingly, quantification by immunochemistry of the enzyme
      itself (ACOX1) revealed that palmitoyl-CoA oxidase enzymatic activity correlates
      with ACOX1 protein level following exposure to diesel, but not following exposure
      to biodiesels. Quantification of CYP4A1, another biomarker of peroxisomal
      proliferation, further indicates that contrary to diesel, the effects of
      biodiesels appear to be independent of this pathway. There are two ACOX1 protein
      isoforms that exhibit different enzymatic activities depending on the substrate.
      The results of our enzymatic assays performed on substrates presenting different
      carbon chain lengths (octanoyl-CoA and palmitoyl-CoA) are compatible with the
      hypothesis of a differential regulation of the ACOX1 isoforms by diesel and
      biodiesels. Further studies will be required to precisely determine the molecular
      mechanisms by which diesel and biodiesels induce palmitoyl-CoA oxidase activity
      in rat liver.

PMID- 22585587
TI  - Psychosocial aspects of preconception consultation in primary care: lessons from
      our experience in clinical genetics.
AB  - To date, little is known about the psychosocial aspects of preconception
      consultation (PCC) in primary care. PCC in primary care is appropriate for
      couples and individuals with a reproductive wish. In PCC, non-genetic and genetic
      risk factors may be identified. Focusing on non-genetic and genetic risk factors
      in PCC requires the use of different counselling strategies and tools in
      optimizing the outcome of pregnancy. Addressing lifestyle alterations requires
      directive counselling, whereas addressing increased genetic risk and its
      subsequent reproductive options requires non-directiveness. When an increased
      genetic risk is detected, couples should be informed about their possibilities
      for not passing on a disease allele. Depending upon the various modes of
      inheritance and reproductive options, couples may face a variety of psychosocial
      challenges. This paper aims to provide insights into the psychosocial impact of
      the genetic aspects of PCC by drawing upon literature and clinical experience in
      the Clinical Genetics department. Furthermore, this paper provides consideration
      for future developments regarding preconception genetic screening.

PMID- 22585589
TI  - Should benzodiazepines still have a role in treating patients with anxiety
      disorders?

PMID- 22585590
TI  - Different safety profiles of risperidone and paliperidone extended-release: a
      double-blind, placebo-controlled trial with healthy volunteers.
AB  - OBJECTIVE: The present study investigated subjective experiences related to
      secondary negative symptoms and cognitive performance in healthy volunteers in
      response to the repeated administration of paliperidone extended-release (ER) and
      risperidone in a double-blind, placebo-controlled trial. METHODS: Participants (n
      = 32) received a fixed dose of one of three study medications for three
      consecutive days: 6 mg of paliperidone ER, 3 mg of risperidone, or placebo.
      Subjects were evaluated at baseline and after the first and third administrations
      of the medications by using the Neuroleptic-Induced Deficit Syndrome Scale and
      the Scale for the Assessment of Negative Symptoms. Cognitive function was
      measured at baseline and after the third administration of the medications by
      using the computerized neuropsychological test. RESULTS: Risperidone was
      associated with more detrimental subjective experiences compared with
      paliperidone ER and placebo (p < .05), and these differences persisted after
      controlling for mental and physical sedation. Analysis of computerized
      neuropsychological test variables revealed significant differences in the changes
      in Stroop word-color test results from baseline between the paliperidone ER and
      risperidone groups (p < .005) and between the placebo and risperidone groups (p <
      .005). CONCLUSIONS: These results suggest that paliperidone ER may have a better
      safety profile than risperidone in terms of negative subjective experiences and
      cognitive function among normal volunteers.

PMID- 22585591
TI  - Khat use is associated with increased response conflict in humans.
AB  - OBJECTIVE: Khat consumption has become a worldwide phenomenon broadening from
      Eastern Africa and the south west of the Arabian Peninsula to ethnic communities
      in the rest of the world. Only few studies have systematically looked into
      cognitive impairments in khat users. We studied whether khat use is associated
      with changes in the emergence and resolution of response conflict, a central
      cognitive control function. METHOD: Khat users (n = 16) and khat-free controls (n
      = 16) were matched in terms of sex, ethnicity, socio-economical situation, age,
      alcohol and cannabis consumption, and IQ (Raven's Progressive Matrices). Groups
      were tested on response conflict, as measured by the Simon task. RESULTS: Khat
      users performed significantly slower than controls and were more strongly
      affected by stimulus-induced response conflict. CONCLUSIONS: Khat use is
      associated with specific impairments in behavioral control: general slowing and
      less efficient resolution of response conflicts, which is likely to impair
      decision making in everyday life.

PMID- 22585592
TI  - Plasma levels of milnacipran and its effectiveness for the treatment of chronic
      pain in the orofacial region.
AB  - OBJECTIVES: This study was performed to assess the relationship between plasma
      levels of milnacipran and its analgesic/antidepressive effect in patients with
      chronic orofacial pain treated with this drug. METHODS: A total of 44 patients
      took milnacipran for 12 weeks. Patients were assessed for their pain and
      depressive symptoms using the visual analog scale (VAS) and Hamilton Depression
      Rating Scale, respectively. The plasma milnacipran level was also assessed at
      week 12. RESULTS: Forty patients completed study treatment and were included in
      the analysis. In these patients, the VAS score at week 12 significantly decreased
      from the baseline score (t = 5.15, p < 0.0001). The dose of milnacipran was
      positively correlated in a linear manner with the plasma level of the drug (Y =
      44.86 + 0.33X, r = 0.54, R(2)  = 0.29, p = 0.0004). A quadratic regression curve
      was plotted between the percentage of decrease in the VAS score and plasma
      milnacipran level (Y = 27.39 + 0.76X - 0.008X(2) , p = 0.048, r = 0.40, R(2)  =
      0.16). On the other hand, no significant relationship was noted between the
      percentage of decrease in the Hamilton Depression Rating Scale score and plasma
      milnacipran level. CONCLUSION: The analgesic effect of milnacipran was suppressed
      in the presence of the plasma level of the drug outside the therapeutic range,
      whereas its antidepressant effect was not affected by its plasma level.

PMID- 22585593
TI  - No involvement of the adenosine A2A receptor in tardive dyskinesia in Russian
      psychiatric inpatients from Siberia.
AB  - BACKGROUND: The adenosine A2A receptor forms a heteromeric complex with the
      striatal dopamine D2 receptor. We examined whether a specific polymorphism in
      adenosine A2A receptor (2592 C/Tins) is associated with tardive dyskinesia.
      METHODS: Tardive dyskinesia was assessed cross-sectionally in 146 Caucasian
      psychiatric inpatients from Siberia. RESULTS: Between-group comparisons of
      genotypic or allelic frequencies showed no statistically significant difference.
      Logistic regression analysis with the occurrence of tardive dyskinesia as
      dependent variable showed no significant association with age, duration of
      illness, gender, and genotype. CONCLUSION: The interaction between the A2A and D2
      receptors seems not involved in the development of tardive dyskinesia.

PMID- 22585594
TI  - Substance misuse trends in South Africa.
AB  - This paper, the first in a series related to the Joint European South African
      Research Network in Anxiety Disorders programme, examines substance use trends in
      South Africa. Alcohol remains the substance with the greatest burden of harm.
      Yet, trends vary by region, with for example methamphetamine being a major driver
      of psychiatric and substance abuse treatment demand in the Western Cape province.
      Heroin use is increasing in several provinces, where rapid intervention is
      required to avoid an epidemic. In particular, the state (the main funder of drug
      services) urgently needs to provide opioid substitution treatment. Apart from an
      inadequate number of treatment services, barriers to treatment are high. Barriers
      are predominantly cost, transport and resource related. Services are also
      impacted by a small and inadequately trained workforce and poor integration with
      mental health services. To adequately intervene with substance use disorders,
      South Africa needs an evidence-based policy and service planning framework that
      forges linkages with the mental health service system.

PMID- 22585595
TI  - Development of a clinical prediction rule to identify patients with neck pain
      likely to benefit from thrust joint manipulation to the cervical spine.
AB  - STUDY DESIGN: Prospective cohort/predictive validity study. OBJECTIVE: To
      determine the predictive validity of selected clinical examination items and to
      develop a clinical prediction rule to determine which patients with neck pain may
      benefit from cervical thrust joint manipulation (TJM) and exercise. BACKGROUND:
      TJM to the cervical spine has been shown to be effective in patients presenting
      with a primary report of neck pain. It would be useful for clinicians to have a
      decision-making tool, such as a clinical prediction rule, that could accurately
      identify which subgroup of patients would respond positively to cervical TJM.
      METHODS: Consecutive patients who presented to physical therapy with a primary
      complaint of neck pain completed a series of self-report measures, then received
      a detailed standardized history and physical examination. After the clinical
      examination, all patients received a standardized treatment regimen consisting of
      cervical TJM and range-of-motion exercise. Depending on response to treatment,
      patients were treated for 1 or 2 sessions over approximately 1 week. At the end
      of their participation in the study, patients were classified as having
      experienced a successful outcome based on a score of +5 ("quite a bit better") or
      higher on the global rating of change scale. Sensitivity, specificity, and
      positive and negative likelihood ratios were calculated for all potential
      predictor variables. Univariate techniques and stepwise logistic regression were
      used to determine the most parsimonious set of variables for prediction of
      treatment success. Variables retained in the regression model were used to
      develop a multivariate clinical prediction rule. RESULTS: Eighty-two patients
      were included in data analysis, of whom 32 (39%) achieved a successful outcome. A
      clinical prediction rule with 4 attributes (symptom duration less than 38 days,
      positive expectation that manipulation will help, side-to-side difference in
      cervical rotation range of motion of 10 degrees  or greater, and pain with
      posteroanterior spring testing of the middle cervical spine) was identified. If 3
      or more of the 4 attributes (positive likelihood ratio of 13.5) were present, the
      probability of experiencing a successful outcome improved from 39% to 90%.
      CONCLUSION: The clinical prediction rule may improve decision making by providing
      the ability to a priori identify patients with neck pain who are likely to
      benefit from cervical TJM and range-of-motion exercise. However, this is only the
      first step in the process of developing and testing a clinical prediction rule,
      as future studies are necessary to validate the results and should include long
      term follow-up and a comparison group. LEVEL OF EVIDENCE: Prognosis, level 2b.

PMID- 22585596
TI  - Progress towards systems of quality measurement that capture the essence of good
      palliative care.

PMID- 22585598
TI  - Three new natural compounds from the root bark essential oil from Xylopia
      aethiopica.
AB  - INTRODUCTION: In the course of on-going work on the characterisation of aromatic
      plants from the Ivory Coast we investigated the composition of the root oil from
      Xylopia aethiopica. OBJECTIVES: The aim of this work was to investigate the
      chemical composition of X. aethiopica root oil and elucidate the structure of two
      new compounds. METHODOLOGY: Analysis of the essential oil was carried out using a
      combination of chromatographic (CC, GC with retention indices) and spectroscopic
      techniques (MS, (13)C-NMR, 2D-NMR). RESULTS: Twenty seven components, accounting
      for 95.6% of the whole composition, were identified including various compounds
      for which spectroscopic data were absent on commercial computerised MS libraries.
      Three compounds are reported for the first time as natural compounds and the
      structure of two new compounds, 4,4-dimethyl-2-vinylcyclohexene and endo-5
      methoxy-3-patchoulene, has been elucidated using extensive two-dimensional NMR
      spectroscopy. CONCLUSION: The composition of X. aethiopica root oil is dominated
      by two dimethylvinylcyclohexene isomers. It differs drastically from the
      composition of leaf and fruit oils of the same plant. The combination of
      analytical techniques appeared crucial for a fruitful analysis.

PMID- 22585599
TI  - Prenatal sonographic diagnosis of mature renal teratoma: a case report.
AB  - Renal teratoma is an extremely rare condition found in adolescents and young
      adults. Here, we report a case in which renal teratoma was diagnosed by fetal
      ultrasound examination. To our knowledge, this is the first report to describe
      the imaging manifestation of renal teratoma in prenatal diagnosis.

PMID- 22585600
TI  - Evidence for BCR-ABL-dependent dysfunctions of iNKT cells from chronic myeloid
      leukemia patients.
AB  - Chronic myeloid leukemia (CML) is a clonal hematopoietic stem-cell malignancy
      characterized by the presence of the chimeric BCR-ABL oncoprotein with
      deregulated tyrosine-kinase (TK) activity. Although conventional T cells are
      acknowledged as important players in the control of CML, a possible modification
      of invariant NKT (iNKT) cells, known for their antitumoral activity, has not been
      established as yet. Here, we showed that the expression of perforin, CD95L, and
      promyelocytic leukemia zinc finger, a transcription factor required for
      maintenance of iNKT cell functions, was reduced or suppressed in CML patients at
      diagnosis, as compared with healthy individuals. The proliferation rate of blood
      iNKT cells in response to their cognate ligand was likewise diminished. These
      functional deficiencies were corrected in patients having achieved complete
      cytogenetic remission following TK inhibitor or IFN-alpha therapy. iNKT cells
      from CML patients in the chronic phase did not display increased TK activity,
      which argued against a direct autonomous action of BCR-ABL. Instead, we found
      that their anergic status originated from both intrinsic and APC-dependent
      dysfunctions. Our data demonstrate that chronic phase CML is associated with
      functional deficiencies of iNKT cells that are restored upon remission. These
      results suggest a possible contribution to disease control by TK inhibitor
      therapies.

PMID- 22585601
TI  - Mutations of SMAD4 account for both LAPS and Myhre syndromes.

PMID- 22585602
TI  - [What do psychiatrists know about the children of their patients?].
AB  - OBJECTIVE: Psychiatry could be a good starting point for preventive work for
      children of mentally ill parents by detecting children who are potentially at
      risk and connecting affected families with preventive services. However, it is
      unclear how much attention clinical psychiatrists pay for children of their
      patients. Therefore, this study examines the knowledge of german psychiatrists
      about the children of their patients and their attitude towards the youth welfare
      and prevention system. METHODS: Seven psychiatric hospitals of one federal state
      in Germany participated in a questionnaire survey. RESULTS: The majority of the
      psychiatrists know whether their patients have children or not, but they can not
      answer differentiate questions of the children's life circumstances or name
      preventive programs for children and their families. Furthermore, psychiatrists
      potentially could forestall preventive programs because of a lack of knowledge
      about the youth welfare. CONCLUSIONS: Psychiatrists need more information about
      the children of their patients and about the general possibilities of prevention
      as well as more knowledge of supportive offers of the youth welfare.

PMID- 22585603
TI  - AKT as locus of cancer angiogenic robustness and fragility.
AB  - Angiogenesis get full robustness in metastatic cancer, relapsed leukemia or
      lymphoma when complex positive feedback loop signaling systems become
      integrative. A cancer hypoxic microenvironment generates positive loops inducing
      formation of the vascular functional shunts. AKT is an upstream angiogenic locus
      of integrative robustness and fragility activated by the positive loops. AKT
      controls two downstream nodes the mTOR and NOS in nodal organization of the
      signaling genes. AKT phosphorylation is regulated by a balance of an
      oxidant/antioxidant. Targeting AKT locus represents new principle to control
      integrative angiogenic robustness by the locus chemotherapy.

PMID- 22585604
TI  - Expression of von Hippel-Lindau gene product (pVHL) and S100P in cystic neoplasms
      of the pancreas--with an implication for their roles in tumorigenesis.
AB  - Our recent study demonstrated the inverse correlation of expression of S100P and
      von Hippel-Lindau gene product (pVHL) in pancreatic intraepithelial neoplasia
      (PanIN) and pancreatic ductal adenocarcinoma (PDA). This study investigates
      whether there is a correlation of expression of these two markers in common
      cystic neoplasms of the pancreas. Immunohistochemical stains for S100P and pVHL
      were performed on 97 cystic neoplasms of the pancreas, including 23 mucinous
      cystic neoplasms (MCNs), 39 intraductal papillary mucinous neoplasms (IPMNs), 12
      solid pseudopapillary tumors (SPTs), and 23 serous microcystic adenomas (SMAs).
      The results demonstrated a nuclear and cytoplasmic staining pattern of S100P in
      91.3% of MCNs and 100% of IPMNs. In contrast, none of the SPTs or SMAs was
      positive for S100P. All IPMNs and SPTs, and all S100P-expressing MCNs were
      negative for pVHL, including 20 MCNs and 20 IPMNs with low-grade dysplasia. All
      cases of SMA were positive for pVHL. Our data suggest 1) the inverse correlation
      of expression of S100P and pVHL in MCN and IPMN is similar to that in PanIN and
      PDA, suggesting a role of these two proteins in early tumorigenesis; 2) the loss
      of pVHL expression in MCN and IPMN supports the recent recategorization of these
      neoplasms without any cytological atypia as low-grade dysplasia instead of
      adenoma; 3) the loss of expression of pVHL in SPT supports the concept of an
      uncertain malignant potential of this entity; and 4) the lack of expression of
      S100P and expression of pVHL in SMA supports the benign nature of this entity.

PMID- 22585605
TI  - Immunohistochemical evaluation of inhibin-alpha in non-small-cell lung carcinomas
      -a pitfall in diagnosing metastatic pulmonary carcinomas.
AB  - CONTEXT: Inhibin-alpha is commonly used in differentiating non-small-cell lung
      carcinoma from certain metastatic carcinomas, but a study on a large series of
      primary lung cancer cases has not yet been published. OBJECTIVE: To establish
      whether non-small-cell lung carcinoma can express inhibin-alpha; if so, caution
      should be exercised when using the molecule to evaluate metastatic lung cancer in
      both lung and extrapulmonary sites. DESIGN: 187 cases of non-small-cell lung
      carcinoma and small-cell lung carcinoma were evaluated for expression of inhibin
      alpha on both routine and tissue microarray sections by immunohistochemistry.
      These cases included 90 mixed or acinar adenocarcinomas, 2 acinar carcinomas with
      mucinous feature, 6 bronchioloalveolar carcinomas, 9 large-cell carcinomas, 2
      adenosquamous carcinomas, 2 sarcomatoid carcinomas, 41 squamous cell carcinomas,
      12 typical carcinoid tumors, 3 atypical carcinoid tumors, 20 small-cell lung
      carcinomas, and 19 cases of normal lung. The staining intensity was graded as
      weak, intermediate, or strong. The distribution was recorded as negative (no
      staining), 1+ (<25%), 2+ (26-50%), 3+ (51-75%), or 4+ (>75%). Cytoplasmic coarse
      granular staining for inhibin-alpha was the indicator for a positive result.
      RESULTS: A subset of primary mixed or acinar and mucin-producing acinar
      carcinomas (10%) and large-cell carcinomas (22%) expressed inhibin-alpha. No
      expression of inhibin alpha was observed in the remaining cancers or normal lung
      samples. CONCLUSION: Since a significant percentage of non-small-cell lung
      carcinoma cases expressed inhibin-alpha, caution should be taken when using
      inhibin-alpha as the key antibody for exclusion of a lung primary in lung and
      other organs.

PMID- 22585606
TI  - Neuron precursor features of spindle cell oncocytoma of adenohypophysis.
AB  - CONTEXT: Spindle cell oncocytoma of the adenohypophysis (SCO) is a non-endocrine
      neoplasm with few recurrent forms described. It arises from the folliculo
      stellate cells of the adenohypophysis. OBJECTIVE: We describe a case of SCO in a
      24-year-old woman and provide pathogenetic information. DESIGN: Hematoxylin-eosin
      (H&E), and immunohistochemistry, with controls, for S100, SMI-311, neurofilament,
      EMA, CD68, GFAP, chromogranin, synaptophysin, and Ki67 were performed. CD44,
      nestin, Gli2, p-Akt(Ser 473) and p-mTOR(Ser 2448) antibodies were applied, and
      each analyte's cellular distribution and intensity were noted. RESULTS: H&E
      showed a proliferation of spindle and polygonal cells with a fascicular pattern,
      without mitoses. There was reactivity for SMI-311, CD44, nestin, S100, EMA, and
      vimentin. Neurofilament, CD68, chromogranin, synaptophysin, and GFAP were not
      expressed. p-Akt and p-mTOR were expressed suggesting mTORC2. Gli2 showed nuclear
      expression in the tumoral cells. CONCLUSIONS: These findings suggest that SCO has
      neuron-like precursor cells. Sonic hedgehog and mTOR pathways are activated.

PMID- 22585607
TI  - BK virus as a potential co-factor for HPV in the development of cervical
      neoplasia.
AB  - Cervical cancer is the third most common type of cancer in women worldwide. A
      persistent infection with high risk (HR) human papillomavirus (HPV) is necessary
      for cervical cancer to occur. However, the great majority of women that are
      infected with HR-HPV will not develop cervical cancer, indicating that HR-HPV
      alone is not adequate to drive the development of cervical cancer, suggesting the
      involvement of cofactors. The BK polyomavirus (BKV) establishes latency near
      cervical tissue in the urogenital tract and is frequently detected in the urine,
      especially in immunosuppressed patients, and hence may coexist with HR-HPV.
      Current experimental evidence indicates that both HR-HPV and BKV are capable of
      altering cell-cycle control and inhibit apoptosis. Therefore, they may act
      additively or synergistically to promote malignant transformation. We hypothesize
      that BKV is a co-factor for HR-HPV in cervical cancer. In this study, we examined
      249 cervical swabs that were submitted for routine HR-HPV screening test in the
      Molecular Diagnostics Laboratory at the University of Texas Medical Branch
      (UTMB). Our results showed that 107 samples contained HR-HPV at an overall rate
      of 43% (107/249); BKV was present in 4 (3.7%) of the 107 HR-HPV positive
      specimens and in 12 (8.5%) of the 142 HR-HPV negative samples with an overall
      positive rate of 6.4% (16/249). Although there was no statistical significance
      between HR-HPV and BKV co-infection (P=0.19, Fisher's exact test), our results
      support the hypothesis that BKV can co-exist with HR-HPV in cervical specimens.

PMID- 22585608
TI  - HER2-positive male breast cancer with thyroid cancer: an institutional report and
      review of literature.
AB  - We report a rare finding of two male breast cancer patients with HER2-positive
      breast cancer who also developed thyroid cancer. We reviewed 45 male breast
      cancer patients treated in our institution from 2003 to 2008. Only five male
      breast cancer patients were HER2-positive. In reviewing the published data, we
      found no cases of thyroid cancer and concurrent breast cancer in men. However,
      breast cancer and thyroid cancer have shown close association in women. This
      finding therefore provokes speculation as to whether we should investigate
      whether women with HER2-positive breast cancer are at a higher risk for thyroid
      cancer. Although this observation seems to be clinically prevalent, publications
      are sparse in clinical research areas linking thyroid cancer to breast cancer.

PMID- 22585609
TI  - Attenuation of tissue oxidative stress by dietary restriction in rats on
      simulated microgravity.
AB  - INTRODUCTION: Physiologic alterations caused by oxidative stress can be assessed
      by measuring tissue malondialdehyde (MDA) levels, a biomarker for oxidative
      stress. The goal of this study is to determine the consequences of a twenty
      percent caloric restriction on the increased oxidative stress documented in
      tissues from rats exposed to simulated microgravity. MATERIALS/METHODS: Three
      groups of male SD rats (N=6 in each group) were used: Group 1, control; Group 2,
      food restricted (20% less food than control); and Group 3, food restricted with
      HLS. Group 3 was suspended after one week on the HLS-restricted diet and
      maintained for 14 days. Tissues harvested on day 14 were measured for MDA levels.
      RESULTS: The body weight gain of Group 2 and Group 3 was reduced as compared to
      that of Group 1 ( p <0.05) with no significant changes in water intakes. MDA
      levels in Group 2 were not different from those of the control group and were
      elevated only in liver tissues (p<0.05). In Group 3, MDA levels in the heart,
      liver, brain, and testes were significantly elevated (p<0.05) compared to the
      levels of Groups 1 and 2. CONCLUSIONS: Food restriction alleviated tissue
      oxidative response in all tissues except for the liver. Excessive stress
      resulting from HLS appeared to have been minimized by dietary restriction in all
      tissues except for the heart, liver, brain, and testes.

PMID- 22585610
TI  - Regulation of iron-related molecules in the rat hippocampus: sex- and age
      associated differences.
AB  - Iron accumulation, especially that of free oxidized ferrous iron, has been shown
      to induce tissue oxidative damage and contribute to brain aging and the
      development of neurodegenerative disease. Here we examine whether sex and
      advanced age affect the expression of iron-related molecules that participate in
      regulating free iron levels (heme oxygenase 1 (HO1), iron-regulatory protein 1
      (IRP1), and ferritin heavy chain (FTH)) and whether changes in the expression of
      these molecules are associated with differences in the expression of alpha
      synuclein (ASN) which is thought to be a critical regulator in the pathogenesis
      of neurodegeneration. Using a well-established aging animal model, we demonstrate
      that the expression of HO1, FTH, and IRP1 mRNAs is higher in the female
      hippocampus than that observed in male Fischer 344/NNiaHSD x Brown Norway/BiNia
      (F344BN) rats, regardless of age group. Consistent with these sex-associated
      alterations in iron-related regulators, the expression of ASN mRNA and protein in
      the female hippocampus was lower than that found in male rats. These results
      suggest a sex-dependent difference in regulating the expression of molecules
      involved in iron metabolism and neurodegeneration. A similar finding in humans,
      if present, may help to shed light on why sex may affect the incidence of
      neurodegenerative disorders.

PMID- 22585611
TI  - Chronic paracetamol treatment influences indices of reactive oxygen species
      accumulation in the aging Fischer 344 X Brown Norway rat aorta.
AB  - Previous reports have demonstrated that increased levels of reactive oxygen
      species (ROS) and alterations in cell signaling characterize aging in the Fischer
      344 X Brown Norway (FBN) rat aorta. Other work has suggested that increases in
      ROS may be related to vascular wall thickening and the development of
      hypertension. Paracetamol (acetaminophen) is a potent antioxidant that has been
      found to diminish free radicals in ischemia-reperfusion studies. However, it
      remains unclear whether chronic paracetamol administration influences signaling
      or ROS accumulation in the aging aorta. FBN rats (27 months old; n=8) were
      subjected to 6 months of treatment with a therapeutic dose of paracetamol (30
      mg/kg/day) and compared to age-matched untreated FBN rat controls (n=8). Compared
      to measurements in the aortae of 6-month old animals, tunica media thickness,
      tissue superoxide levels, and protein oxidation levels were 38 +/- 7%, 92 +/-
      31%, and 7 +/- 2% higher in the aortae of 33-month control animals (p <=0.05).
      Chronic paracetamol treatment decreased tunica media thickness and the amount of
      oxidized protein by 13 +/- 4% and 30 +/- 1%, respectively (p <=0.05). This
      finding of diminished aortic thickening was associated with increased
      phosphorylation (activation) of the mitogen activated protein kinases and
      diminished levels of the anti-apoptotic protein Bcl-2. Taken together, these data
      suggest that chronic paracetamol treatment may decrease the deleterious effects
      of aging in the FBN rat aorta.

PMID- 22585612
TI  - C. glycolicum as the sole cause of bacteremia in a patient with acute
      cholecystitis.
AB  - Here we describe a case of Clostridia glycolicum (C. glycolicum) bacteremia in a
      bed-ridden elderly man with chronic illnesses. The bacterium was identified by
      the Remel RapID ANA II System. We believe that this is the fifth published report
      of human illness caused by this bacterium. In the four previously reported cases,
      C. glycolicum was found in cultures with other bacteria. This is the first
      reported case in which C. glycolicum was the sole causative agent of disease.

PMID- 22585613
TI  - Analysis of reagent lot-to-lot comparability tests in five immunoassay items.
AB  - We investigated the degree of lot-to-lot reagent variation for 5 common
      immunoassay items. We measured the commercial as well as in-house controls for
      alpha-fetoprotein (AFP), ferritin, CA19-9, quantitative hepatitis B surface
      antigen (HBsAg), and hepatitis B surface antibody (anti-HBs) 10 times each by
      using both the old and the new lot of reagents whenever a reagent lot was
      changed, over a period of 10 months. The differences in the mean control values,
      the percent difference (% difference), and the difference to between-run standard
      deviation ratio (D:SD ratio) between successive lots were calculated. The %
      difference in mean control values between 2 reagent lots ranged from 0.1 to 17.5%
      for AFP, 1.0 to 18.6% for ferritin, 0.6 to 14.3% for CA19-9, 0.6 to 16.2% for
      HBsAg, and 0.1 to 17.7% for anti-HBs except negative controls of HBsAg and anti
      HBs. The maximum D:SD ratios between 2 lots were 4.37 for AFP, 4.39 for ferritin,
      2.43 for CA19-9, 1.64 for HBsAg, and 4.16 for anti-HBs. Thus, we have experienced
      extensive variability in lot-to-lot reagent variation for 5 immunoassay items,
      indicating that reagent lot-to-lot comparability tests should be continuously
      performed and that laboratories should determine their own acceptance criteria
      for each item.

PMID- 22585614
TI  - Rapid detection of bacterial contamination of platelet-rich plasma-derived
      platelet concentrates using flow cytometry.
AB  - Flow cytometry can be used to detect bacterial contamination of platelet
      products. In this study, we investigated whether the incubation of a minimal
      volume of platelet-rich plasma (PRP)-derived platelet concentrates (PCs) with
      growth medium improved the analytical sensitivity of flow cytometry. Five
      bacterial strains (Staphylococcus aureus, Staphylococcus epidermidis, Bacillus
      cereus, Klebsiella pneumoniae, and Escherichia coli) were used. Platelets were
      inoculated with 10, 10(2), and 10(3) CFUs per mL; 0.5 mL, 1.0 mL, and 2.0 mL
      aliquots of spiked platelets were incubated with growth medium at 37 degrees C
      for 24 hours. During the incubation period, the numbers of events were analyzed
      every 4 hours by flow cytometry. We could detect a low concentration (10 CFUs per
      mL) of bacteria in a small volume (minimum 0.5 mL) of PCs. Irrespective of
      spiking concentrations and incubation volumes, the detection times of S. aureus
      and S. epidermidis were 24 hours or less, while those of B. cereus, K.
      pneumoniae, and E. coli were 16 hours or less. A higher spiking concentration
      made it possible to shorten the detection time. The numbers of detected bacteria
      increased during the incubation. However, the graphs corresponding to K.
      pneumoniae and E. coli showed peak levels and decreasing patterns during the
      incubation period. The incubation of small volumes of PC with growth medium
      increased the analytical sensitivity of flow cytometry for bacterial detection.
      Therefore, flow cytometry can serve as a useful method for sterility testing
      using PRP-derived PCs with only low levels of consequent platelet loss.

PMID- 22585615
TI  - Isolation of rare coagulase-negative isolates in immunocompromised patients:
      Staphylococcus gallinarum, Staphylococcus pettenkoferi and Staphylococcus
      pasteuri.
AB  - Herein, we describe the isolation of Staphylococcus pasteuri, Staphylococcus
      pettenkoferi and Staphylococcus gallinarum and summarize the clinical
      characteristics of five patients. Cases were identified over a 2-year
      surveillance period that identified the respective strains using microbiologic
      and molecular methods. These data suggest that rare coagulase-negative
      staphylococcal infections may be under-diagnosed due to difficulties associated
      with routine clinical laboratory diagnostic methods.

PMID- 22585616
TI  - Reversal of FLT3 mutational status and sustained expression of NPM1 mutation in
      paired presentation, and relapse samples in a patient with acute myeloid
      leukemia.
AB  - We report a case of de novo acute myeloid leukemia (AML) with unstable FLT3 gene
      mutations and stable NPM1 mutation. FLT3/D835 and NPM1 (Type A) mutations were
      detected upon diagnosis. During the relapse, the FLT3/D835 mutation changed to an
      FLT3/ITD mutation while the NPM1 (Type A) mutation was retained. Cytogenetic
      analyses showed the normal karyotype at diagnosis and relapse. Our findings raise
      interesting questions about the significance of these mutations in the
      leukemogenic process, about their stability during the evolution of the disease,
      and regarding the selection of appropriate molecular markers for the monitoring
      of minimal residual disease.

PMID- 22585617
TI  - Prevalence of the plasmid-mediated quinolone resistance genes, aac(6')-Ib-cr,
      qepA, and oqxAB in clinical isolates of extended-spectrum beta-lactamase (ESBL)
      producing Escherichia coli and Klebsiella pneumoniae in Korea.
AB  - In this study, we sought to determine the prevalence of the plasmid-mediated
      quinolone resistance (PMQR) genes aac(6')-Ib-cr, qepA, and oqxAB in extended
      spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella
      pneumoniae clinical isolates in South Korea. In total, 104 isolates (63 E. coli
      and 41 K. pneumoniae) were collected. We found that 23 of the 63 (36.5%) E. coli
      and nine of the 41 (22.0%) K. pneumoniae isolates were positive for aac(6')-Ib
      cr. No isolate was positive for qepA, while transferable oqxAB was detected only
      in 10 (24.4%) K. pneumoniae isolates. Among the 32 aac(6')-Ib-cr-positive
      isolates, 30 (93.8%) were positive for both aac(6')-Ib-cr and bla(CTX-M) (CTX-M
      15, -14, and -57). Our results suggest that PMQR determinants are highly
      prevalent in ESBL-producing E. coli and K. pneumoniae isolates in Korea.

PMID- 22585618
TI  - Ligustrazine attenuates myocardial ischemia reperfusion injury in rats by
      activating the phosphatidylinositol 3-kinase/Akt pathway.

PMID- 22585620
TI  - Exploring the professional values of Australian physiotherapists.
AB  - BACKGROUND AND PURPOSE: A profession's values guide daily practice and
      professional behaviours. They clarify what professionalism means to a profession,
      by providing insight into the values that members of the profession aim to uphold
      and profess. There has been limited research into the values of the Australian
      physiotherapy profession, and as such, the values that guide practice and
      constitute professionalism are not explicit. This study aimed to make a
      preliminary identification of the values of the profession, by exploring the
      shared professional values of 14 Australian physiotherapists. METHODS: This study
      was guided by a qualitative approach and constructivist paradigm. Purposive
      sampling was employed to identify physiotherapists who could contribute rich
      information to the study. Semi-structured interviews were conducted and analysed
      using an inductive data analysis method. RESULTS: The emerging professional
      values formed three main themes. The first theme, 'the patient and the patient
      therapist partnership', incorporated values such as having patient trust and
      working collaboratively with patients. The theme labelled 'physiotherapy
      knowledge, skills and practice' included the values of having an evidence base
      and respecting professional boundaries. The last theme, 'altruistic values', was
      inclusive of values such as honesty, empathy and caring. The values that emerged
      went beyond philanthropic values, to values that guided every day practice,
      professional relationships and the responsibilities of being a professional.
      CONCLUSION: The results contribute to research orientated towards identifying the
      values of the profession and in doing so, clarifying what professionalism means
      to the Australian physiotherapy profession. Differences between the values
      identified by the American Physical Therapy Association and the study reported in
      this paper highlight the importance of identifying the values of the profession
      within the Australian context. In terms of practice implications,
      physiotherapists may be prompted to reflect on their values and how these values
      align with those of their patients.

PMID- 22585619
TI  - Effect of zinc supplementation on type 2 diabetes parameters and liver
      metallothionein expressions in Wistar rats.
AB  - Zinc is a trace metal and acts as an active component of various enzymes. Zinc
      deficiency has been suggested to be associated with the development of diabetes.
      The present study investigated the role of zinc supplementation on prevention of
      diabetic conditions. A double-disease model mimicking hyperlipidemia and type 2
      diabetes was created by applying high-fat diet and streptozotocin (STZ) to Wistar
      rats. We demonstrated that zinc supplementation improved symptoms of diabetes
      such as polydipsia and increased serum level of high-density lipoprotein
      cholesterol, indicating that zinc supplementation has a potential beneficial
      effect on diabetic conditions. The level of maldondialdehyde (MDA), an oxidative
      stress marker, was reduced in liver by zinc supplementation in high fat-fed rats
      with or without STZ injection. Meanwhile, we observed an increase in the
      expression of metallothioneins (MTs) in liver of rats treated with zinc. This
      suggests that the induction of MTs in liver, which has been shown to be important
      in scavenging free radicals, could be one of the underlying mechanisms of zinc
      supplementation on reducing MDA levels in liver. Finally, we found that zinc
      levels in liver were increased while there was no change in serum zinc levels,
      indicating that local zinc level might be a critical factor for the induction of
      MTs. Also, the level of MTs could potentially be an index of zinc
      bioavailability. Taken together, these results suggest that both zinc and MT
      could play an important role in balancing nutrition and metabolism to prevent
      diabetic development.

PMID- 22585621
TI  - The Functional Movement Screen: a reliability study.
AB  - STUDY DESIGN: Reliability study. OBJECTIVES: To determine intrarater test-retest
      and interrater reliability of the Functional Movement Screen (FMS) among novice
      raters. BACKGROUND: The FMS is used by various examiners to assess movement and
      predict time-loss injuries in diverse populations (eg, youth to professional
      athletes, firefighters, military service members) of active participants.
      Unfortunately, critical analysis of the reliability of the FMS is currently
      limited to 1 sample of active college-age participants. METHODS: Sixty-four
      active-duty service members (mean +/- SD age, 25.2 +/- 3.8 years; body mass
      index, 25.1 +/- 3.1 kg/m2) without a history of injury were enrolled.
      Participants completed the 7 component tests of the FMS in a counterbalanced
      order. Each component test was scored on an ordinal scale (0 to 3 points),
      resulting in a composite score ranging from 0 to 21 points. Intrarater test
      retest reliability was assessed between baseline scores and those obtained with
      repeated testing performed 48 to 72 hours later. Interrater reliability was based
      on the assessment from 2 raters, selected from a pool of 8 novice raters, who
      assessed the same movements on day 2 simultaneously. Descriptive statistics,
      weighted kappa (kappaw), and percent agreement were calculated on component
      scores. Intraclass correlation coefficients (ICCs), standard error of the
      measurement, minimal detectable change (MDC95), and associated 95% confidence
      intervals (CIs) were calculated on composite scores. RESULTS: The average +/- SD
      score on the FMS was 15.7 +/- 0.2 points, with 15.6% (n = 10) of the participants
      scoring less than or equal to 14 points, the recommended cutoff for predicting
      time-loss injuries. The intrarater test-retest and interrater reliability of the
      FMS composite score resulted in an ICC3,1 of 0.76 (95% CI: 0.63, 0.85) and an
      ICC2,1 of 0.74 (95% CI: 0.60, 0.83), respectively. The standard error of the
      measurement of the composite test was within 1 point, and the MDC95 values were
      2.1 and 2.5 points on the 21-point scale for interrater and intrarater
      reliability, respectively. The interrater agreement of the component scores
      ranged from moderate to excellent (kappaw = 0.45-0.82). CONCLUSION: Among novice
      raters, the FMS composite score demonstrated moderate to good interrater and
      intrarater reliability, with acceptable levels of measurement error. The measures
      of reliability and measurement error were similar for both intrarater reliability
      that repeated the assessment of the movement patterns over a 48-to-72-hour period
      and interrater reliability that had 2 raters assess the same movement pattern
      simultaneously. The interrater agreement of the FMS component scores was good to
      excellent for the push-up, quadruped, shoulder mobility, straight leg raise,
      squat, hurdle, and lunge. Only 15.6% (n = 10) of the participants were identified
      to be at risk for injury based on previously published cutoff values.

PMID- 22585622
TI  - Notch activation on effector T cells increases their sensitivity to Treg cell
      mediated suppression through upregulation of TGF-betaRII expression.
AB  - Notch proteins play an important role in embryonic development and cell-fate
      decisions. Notch influences also the activation and differentiation of peripheral
      T cells. Here, we investigated whether Notch signaling modulates the response of
      effector T cells to regulatory T (Treg) cells. Pre-exposure of CD4(+) CD25(-) 
      effector T cells to the Notch ligands Delta-4 and Jagged-1, but not Delta-1,
      increases significantly effector T-cell sensitivity to Treg cell-mediated
      suppression through upregulation of TGF-betaRII expression and increased levels
      of the phosphorylated form of the Smad 3 protein. This effect is relieved by anti
      TGF-beta Abs. We demonstrate that HES (hairy and enhancer of split), the main
      transcription factor downstream of Notch, induces strong transactivation of TGF
      betaRII by binding the TGF-betaRII promoter through its DNA-binding domain. Thus,
      the crosstalk between Notch and the TGF-beta pathway leads to potentiation of the
      suppressive effect of Treg cells.

PMID- 22585626
TI  - Safety, Efficacy, and Complexities in the ART Laboratory.

PMID- 22585627
TI  - Safety, efficacy, and complexities in ART practice: physician commentary.
AB  - There are few patient care processes for which a team approach is more important
      than for assisted reproduction. Close, continuous communication is required at
      many levels among physicians, nursing staff, therapists, the various
      laboratories, and patients. Quality of care is associated with the reduction of
      medical errors through processes of risk management, mechanisms to allow the safe
      evolution of assisted reproductive technology care within the clinic, and how
      clinics ethically communicate with team members and with patients through
      informed consent and direct and honest interaction.

PMID- 22585628
TI  - Patient and tissue identification in the assisted reproductive technology
      laboratory.
AB  - Several high-profile cases involving in vitro fertilization have recently
      received considerable media attention and highlight the importance of assuring
      patient and tissue identification. Within the assisted reproductive technology
      (ART) laboratory, there are many steps where wrong patient or tissue identity
      could have drastic results. Erroneous identity can result in tragic consequences
      for the patient, the laboratory, and for those working in the program as a whole.
      Such errors can result in enormous psychological and financial costs, as well as
      a loss in confidence. There are several critical steps that should be taken every
      single time and for each specific procedure performed in the ART laboratory to
      ensure the correct identification of patients and their tissue. These steps
      should be detailed in protocols that include the method of identification, the
      two unique identifiers that will be used, the sources of these identifiers, and
      often a system in which more than one person is involved in the identification.
      Each protocol should ideally include a checklist that is actively used for the
      implementation of each procedure. The protocol should also indicate what to do if
      the identification does not match up, including rapid handling and notification
      of the patient involved in the error. All ART laboratories should instill in
      their employees an atmosphere of full and open disclosure for cases where
      mistakes are made.

PMID- 22585629
TI  - Importance of supply integrity for in vitro fertilization and embryo culture.
AB  - The quality of in vitro culture conditions is a key component of a successful
      clinical embryology laboratory. Many, but not all, supplies used in the
      embryology laboratory are screened by the supplier with a bioassay. Embryology
      laboratories use a variety of approaches to verify the quality of mineral oil,
      protein, and disposables before clinical use; however, a best practice has not
      been determined. Some laboratories test every supply, even those already screened
      by the supplier, whereas other laboratories perform as little testing as
      possible. Despite screening by the supplier, recent reports of embryo toxicity,
      specifically with mineral oil, highlight that the integrity of the supply system
      has gaps. This review describes current bioassay quality control testing and
      discusses how it applies to screening of products with documented lot-to-lot
      variation.

PMID- 22585630
TI  - Does the European Union Tissues and Cells Directive improve quality in the in
      vitro fertilization laboratory? A case study in a tertiary referral center.
AB  - Since 2004, assisted conception is encompassed by the European Directive on the
      Quality and Safety of Tissues and Cells (2004/23/EC). The aim of a standard for
      quality and safety is to minimize risks of errors, contamination, and accidents
      and to maximize efficiency of use. This article presents a case study of the
      implementation of the Tissues and Cells Directive in the Leuven University
      Fertility Center (LUFC) with a focus on the assisted reproductive technologies
      laboratory with respect to laboratory facilities, quality management system,
      traceability, storage conditions as well as serological screening. Although the
      current European Union (EU) Directive can be considered a step in the right
      direction to improve patient safety, questions remain as to whether the
      implementation of this EU Directive, requiring extra time and money, has resulted
      in higher quality with respect to the quality dimensions of effectiveness,
      efficiency, timeliness, equity, and patient centeredness.

PMID- 22585631
TI  - In vitro oocyte maturation: current status.
AB  - Due to its numerous clinical applications, in vitro maturation (IVM) has emerged
      as a significant topic in the field of assisted reproduction. IVM of germinal
      vesicle breakdown/metaphase I and germinal vesicle stage oocytes collected from
      in vitro fertilization (IVF) superovulation cycles are commonly applied with
      unsatisfactory results. The biological aspect of this so-called rescue in vitro
      oocyte maturation greatly differs from the actual IVM practice. In the latter,
      immature oocytes are obtained from small antral follicles of unprimed or
      minimally stimulated cycles aiming to avoid ovarian hyperstimulation syndrome in
      high-risk patients or simply as an alternative to conventional IVF in normo
      ovulatory patients. Over the past decade, cases reports regarding IVM have been
      sporadically reported, with ~25 peer-reviewed articles currently available. These
      studies present variable outcomes and deal with clinical approaches about
      selecting the most appropriate patient population that could benefit from IVM
      technology. Although some of the studies are encouraging, the vast majority
      includes small sample sizes, thus making the data rather inconclusive. As such
      there is a certain reserve in the IVF community to embark on treatment cycles for
      IVM in routine use. Laboratory parameters play an important role in the success
      of IVM, and research for optimal culture conditions is warranted. Existing data
      from newborns assure us that IVM may be a safe procedure provided in assisted
      reproductive technology. When optimized, it will serve, not only for infertile
      patients, but also as a more patient-friendly alternative than standard
      controlled ovarian stimulation to obtain oocytes for donation or preservation of
      fecundity.

PMID- 22585632
TI  - Advances in embryo culture systems.
AB  - The growth of mammalian embryos in the laboratory has progressed nicely over the
      last 60 to 70 years. This has been important for basic studies of preimplantation
      embryo regulation of growth, development, and differentiation. It has also been
      critical for the establishment of assisted reproductive technologies in the
      clinical setting to treat infertility. During the first 40 to 50 years, the
      primary focus was on defining soluble media components, which fortunately has
      yielded improved success in the culture of embryos. More recently, attention has
      shifted to other aspects of culture beyond media composition. In this review we
      discuss recent advances in preimplantation embryo culture that deal with
      modifying the insoluble culture environment, producing culture environments that
      are dynamic and not static, systems that allow more precise gas phase and/or
      media pH regulation/monitoring, and platforms that integrate with culture systems
      to allow analysis of embryos and thus assist in selection of the embryos with the
      greatest implantation potential.

PMID- 22585633
TI  - Day 2 transfer in clinical ART.
AB  - Over the past 20 years, numerous techniques have enhanced assisted reproductive
      technology outcomes to help couples have >60,000 infants in the United States in
      2008. Several different days for embryo transfers have been studied, but debate
      for the best timing of embryo transfer is still ongoing. With growing concern
      about multiple gestations and neonatal outcomes, early cleavage stage embryo
      transfer with novel embryo selection tools may be attractive to some patients and
      in vitro fertilization programs. In this review, we summarize clinical and basic
      studies relating to the timing of embryo transfer and highlight the possibilities
      of safe embryo transfer by combining advanced embryo screening tools with
      potentially high efficiency and low adverse effects on clinical outcome.

PMID- 22585634
TI  - To transfer fresh or thawed embryos?
AB  - Worldwide freezing and thawing of embryos has been increasingly used since the
      first infant was born as a result of this technique in 1984. The use of frozen
      embryo replacement (FER) currently even exceeds the number of fresh cycles
      performed in some countries. This article discusses the pros and cons of FER
      versus fresh-embryo transfer with regard to both single-cycle and cumulative
      pregnancy and delivery rates. The review discusses the obvious advantages of FER:
      minimizing the proportion of pharmacological and surgical treatments, and
      lowering the risk of ovarian hyperstimulation syndrome and multiple pregnancies,
      thereby increasing the safety for mother and child. Finally the article describes
      the accumulating literature on perinatal and long-term child outcome after
      transfer of frozen/thawed embryos, including a discussion on the concerns
      regarding cryo techniques and their possible roles in the subsequent development
      of fetus and child. Because larger and more detailed data sets are available for
      early cleavage-stage embryo freezing and slow freezing, they are the main focus
      of this review.

PMID- 22585635
TI  - Comprehensive chromosome screening and embryo selection: moving toward single
      euploid blastocyst transfer.
AB  - Interest in using aneuploidy screening to select embryos has been renewed with
      the introduction of new methods for comprehensive chromosome screening (CCS) that
      evaluate all 24 chromosomes. With a series of experiments providing level I
      evidence of accuracy, reliability, safety, predictive value, and clinical
      efficacy, CCS-based selection of a single euploid blastocyst may provide an
      opportunity to finally realize the potential benefits and practical application
      of elective single embryo transfer. Furthermore, by incorporating CCS into
      research and development to control for chromosomal contribution to reproductive
      potential, additional biomarkers may now be more readily identified that help to
      further enhance the efficacy of embryo selection technology. This review
      describes the critical components of a valid CCS embryo selection methodology and
      discusses the limitations and opportunities for future routine application in
      reproductive medicine.

PMID- 22585636
TI  - Unique patient issues: early interventions and management.
AB  - Patient cases that present with recurring fertilization failure or complete
      abnormality in either the oocytes or sperm before fertilization are uncommon, yet
      they are devastating. This review presents several such instances, including
      oocyte maturation blocks, empty follicle syndrome, oocyte activation failures,
      defects in sperm phospholipase C isoform zeta, sperm structural anomalies,
      spontaneous oocyte activation, and unexplained cases. Diagnostic efforts have not
      only provided insight into possible etiologies but also have helped manage such
      challenging cases. Interventions may comprise cellular, molecular, or genetic
      analyses of gametes, as well as functional assays and/or modified treatment
      strategies. Consequently, infertility professionals can increasingly rely on
      evidence-based counseling with respect to prognosis and treatment options.

PMID- 22585637
TI  - One-step preparative separation of two polyhydroxystilbenes from Rheum
      likiangense Sam. by high-speed counter-current chromatography.
AB  - INTRODUCTION: The official rhubarb species have frequently been investigated for
      their hydroxyanthraquinone components and associated pharmacological properties.
      However, other unofficial rhubarb species were rarely studied until
      polyhydroxystilbenes (PHS), which commonly occur in the unofficial rhubarb,
      revealed a range of potential bioactivities. Hence, there has been increasing
      interest in the efficient preparation of high-purity PHS for pharmacological and
      clinical trials. OBJECTIVE: To develop a suitable method for large-scale
      preparative separation of PHS from the rhizome of Rheum likiangense Sam. by high
      speed counter-current chromatography (HSCCC). RESULTS: Two PHS compounds were
      isolated successfully within 440 min using a solvent system consisting of
      methanol:n-butanol:chloroform:water (2:0.5:3:3, v/v/v/v). Eighty-four milligrams
      of desoxyrhaponticin with 98.2% purity and 148 mg of rhaponticin with 95.3%
      purity were respectively yielded from 1.5 g of crude extract in the single, one
      step operation. CONCLUSION: An optimised HSCCC method has been established for
      large-scale preparative separation of PHS compounds from Rheum likiangense Sam.

PMID- 22585638
TI  - An optimal design for patient-specific templates for pedicle spine screws
      placement.
AB  - BACKGROUND: Currently, pedicle screws are positioned using a free-hand technique
      or under fluoroscopic guidance, with error in the range 10-40%, depending on the
      skill of the surgeon. METHODS: After spine CT acquisition, each vertebra is
      segmented and the surgeon plans screw positioning in a virtual environment, then
      the template is designed around the chosen trajectories. This design is based on
      surgical and mechanical considerations to obtain an optimal solution to guarantee
      template stability, simple positioning and minimized intervention invasiveness.
      In vitro evaluation on synthetic spine models and ex vivo animal tests on porcine
      specimens were performed, with the insertion of 28 Kirschner wires. RESULTS:
      During the in vitro tests, all the surgeons rendered positive evaluations
      regarding the device and considered template placement to be easy. Ex vivo tests
      were evaluated by CT examination, which showed that 96.5% of the Kirschner wires
      had been correctly inserted. CONCLUSIONS: The proposed solution is a promising,
      simple, highly precise, low-cost solution to safely performing posterior
      stabilization. Such a solution would be of interest even in hospitals in which a
      few spine interventions are performed per year, and for which it is not
      reasonable to purchase the equipment required for robotic or navigated
      approaches.

PMID- 22585639
TI  - [Sudden cardiac death of rhythmic origin in athletes: literature review].
AB  - The sudden death in athletes is, in the vast majority of cases, related to
      ventricular fibrillation, often in a subject with unknown cardiovascular
      abnormality; this dramatic event has a significant impact on society and the
      medical profession. We conducted through a literature review an analysis of data
      on sudden cardiac death of rhythmic origin in athletes; sudden death may be
      cardiovascular in 95.3% of cases and related to ventricular arrhythmia in 88%
      cases. The main causes are: hypertrophic cardiomyopathy, congenital anomalies of
      coronary arteries, and arhythmogenic right ventricular dysplasia for athletes
      under 35 years, and atherosclerosis beyond 35 years. Prevention is based on three
      main areas: the medical assessment and screening for cardiovascular disease; the
      chain of survival; the education of the athlete and the public. All these
      measures should improve significantly the survival prognosis of patients
      suffering from these accidents.

PMID- 22585640
TI  - [24-hour esophageal impedance-ph monitoring: technical aspects, indications and
      results].
AB  - BACKGROUND: Classical techniques like endoscopy and esophageal pH-metry are the
      gold standard to study patients with symptoms related to gastroesophageal reflux
      disease. Although these techniques have been useful over the years both for
      diagnosis and therapeutic guidance, there are still many patients with typical or
      atypical gastroesophageal reflux disease symptoms with normal endoscopy and pH
      metry that do not respond adequately to antisecretory therapy. Ambulatory
      esophageal impedance-pH monitoring is a new technique that can be used to
      evaluate all types of gastroesophageal reflux, achieving higher rates of
      sensitivity and specificity than standard techniques. AIM: To precise the
      technical aspects of the esophageal impedancepH monitoring, indications and
      results of this technique in clinical practice. METHODS: Literature revue of the
      esophageal impedance - pH monitoring Results: Combined multichannel intraluminal
      impedance and pH monitoring is a new technique that can be used to evaluate both
      bolus transport and all types of reflux (acid, weakly acidic and weakly
      alkaline), without radiation hazards. With this technique, higher rates of
      sensitivity and specificity than standard techniques are obtained in the
      diagnosis of pathological gastroesophageal reflux. The technique has also been
      used in the evaluation of atypical gastroesophageal reflux symptoms, in the
      assessment of the association of different patterns of reflux with symptoms, and
      in the evaluation of therapeutic outcome mainly in patients with refractory
      gastroesophageal reflux disease. CONCLUSION: The esophageal impedance represents
      real progress in understanding the different mechanisms involved in the
      pathophysiology of gastroesophageal reflux. This technique should also allow a
      better understanding of the responsibility of non-acid reflux in special clinical
      situations, such as patients resistant to antisecretory or extra-intestinal
      manifestations of gastroesophageal reflux.

PMID- 22585641
TI  - [Transfusion safety: state of the arts (ART)].
AB  - BACKGROUND: Blood transfusion is a high risk activity. AIM: To evaluate
      transfusion safety in planned cardiac surgery. METHODS: This study was conducted
      in the blood bank of the Rabta Hospital in two phases: a phase to observe
      transfusion acts followed by corrective actions and a phase to evaluate the
      impacts of these corrections on the transfusion practices. Characteristics of the
      potentially transfused patients, the eventually prescribed, dispensed and
      transfused blood products and transfusion practices were studied. RESULTS: During
      the observation phase, 70 patients were enrolled, 51 potentially transfused.
      Weaknesses concerned the mention of phenotype and transfusion history when
      ordering blood components as well as the double ABO/D group typing, the phenotype
      and the cross match performing. Final bedside controls were done in a wrong way.
      The distribution and the blood administration were established respectively for
      208 and 232 blood products. The traceability was established for 86 blood
      products. During the evaluation phase, 30 patients were enrolled, 15 potentially
      transfused. Improvement was achieved in the transfusion history notification,
      phenotype and antibodies screen performing and cross matching. CONCLUSION:
      Optimisation of blood transfusion can be conceived only with collaboration
      between the different transfusion structures.

PMID- 22585642
TI  - [Cervical ripening at term. A randomized and prospective study: Misoprotol versus
      dinoprostone].
AB  - AIM: To compare the efficacy and safety of cervical ripening at term by vaginal
      Misoprostol and Dinoprostone. METHODS: We performed a prospective randomized
      study on cervical ripening with misoprostol and dinoprostone in the third
      trimester of pregnancy. 300 patients have been divided into two groups: one
      consisted by 150 patients who received Misoprostol (Cytotec (r)) and the second
      consisted by 150 patients who received Dinoprostone (Prepidil (r)). RESULTS:
      Analysis of our results allowed to reveal: a significant decrease in the time of
      entry into work for the Misoprostol group (9.08 hours versus 12.51 hours, p =
      0.007), a significant reduction delivery time (14.48 hours versus 19.30 hours, p
      = 0.001). Moreover, the birth rate in the first 24 hours after the first dose was
      significantly higher in the Misoprostol group (86.7% versus 72.7%, p = 0.003).
      The use of oxytocin was significantly reduced with Misoprostol (44% versus 58.7%,
      p = 0.01). The mode of delivery was not influenced by membership in one or other
      of the two groups. CONCLUSION: Misoprostol seems an interesting molecule for
      cervical ripening and labor induction.

PMID- 22585643
TI  - [Percutaneous vertebroplasty for pain relief in patients with osteoporotic spine
      fractures].
AB  - BACKGROUND: Percutaneous vertebroplasty (PVP) is an interventional radiology
      technique where pathological vertebral bodies are filled with acrylic cement.
      This method is used to strengthen the vertebral body and reduce pain in certain
      diseases involving the vertebrae such as osteoporosis. AIM: To evaluated PVP in
      symptomatic osteoporotic vertebral fractures after failure of conservative
      management. METHODS: Between November 2008 to December 2009, PVP was performed
      for osteoporotic vertebral fractures i 12 consecutive patients in a single
      institution. Medium term (3 days and 15 days post PVP) and long term follow up (1
      month and 3 months post PVP) consisted in the evaluation of residual or secondary
      pain using Huskisson's visual analogue scale. RESULTS: A total of 20 vertebrae
      were treated. Mean follow up was 80 days (30-90 days). Significant symptomatic
      improvement (p=0.002) was noted with pre PVP pain score of 7.4 (+/-1.6 ), 3 days
      post PVP score of 4.1 (+/-2.1), 15 days post PVP score of 1.8 (+/-1.1), 1 month
      post PVP score of 1.22 (+/-1.06) and 3 months post score of 1.4 (+/-1.14).
      CONCLUSION: PVP appears to be an effective technique in the treatment of
      symptomatic osteoporotic vertebral fractures with approximately 94% of
      satisfactory results in the short and medium term period.

PMID- 22585644
TI  - [Performances of imaging investigations and scintigraphy for pre operative
      hyperparathyroidism].
AB  - BACKGROUND: Hyperparathyroidism is a frequent affection. Therapeutic management
      is based on surgical removal of pathological glands. Therapeutic results are
      ameliorated thanks to preoperative imaging approach. AIM: To evaluate
      performances of different imaging investigations and scintigraphy for
      preoperative parathyroid localization. METHODS: Retrospective study about 26
      patients with confirmed hyperparathyroidism. RESULTS: After radio-surgical and
      histological correlation, scintigraphy showed the best rate of sensitivity
      (92.3%), compared to other morphologic imaging (ultrasonography: 66.6%, CT-scan:
      33.3% and MRI: 66.6%). The specificity was the same (100 %). No difference was
      obseved for both scintigraphic modalities. CONCLUSION: Our results compared to
      the literature showed that scintigraphy is the most satisfying for preoperative
      localization of abnormal parathyroid glands in hyperparathyroidism.

PMID- 22585645
TI  - [Clinical and evolutionary characteristics of bipolar disorder according to the
      polarity of the first episode].
AB  - BACKGROUND: The polarity of the inaugural episode seems to determine the clinical
      and evolutionary profile of bipolar disorder. AIM: To study the clinical and
      evolutionary characteristics bipolar disorder according to the polarity of the
      first episode. METHODS: We undertook a retrospective, descriptive and comparative
      study including all the patients reached of bipolar disorder I and II (DSM IV TR)
      who were hospitalized between January 1 2000 and December 31 2006. The minimal
      duration of follow-up was 4 years. Patients were divided into two groups
      according to the polarity of the first episode: maniac or hypomaniaque and
      depressive. The characteristics sociodemographic, clinical, evolutionary and
      therapeutic were raised and compared between the two groups. RESULTS: The sample
      was composed of 38 patients (23 men and 15 women). The first episode was of
      polarity maniac in 57.89% of cases. This mode of beginning was related to a later
      polarity preferentially maniac, more often punctuated of characteristics
      psychotics with a sur representation of the addictives conduits and bipolar
      disorder of type I an episode index of depressive polarity was associated to more
      chronic evolution, marked by a stronger recurrence of episodes particularly
      depressive episodes, with a raised suicidal risk and a high representation of the
      bipolar disorder II. CONCLUSION: The clinical and evolutionary profile of the
      bipolar disorder seems strongly related to the polarity of the first episode. The
      strategies of prevention must take account of the inaugural polarity.

PMID- 22585646
TI  - [Risk factors of children overweight and obesity].
AB  - BACKGROUND: The increase of the prevalence of children obesity in some countries
      as Tunisia, necessitate to welling known risk factors for obesity, to prevent and
      early management. AIMS: To determine the prevalence of overweight and of obesity
      in a group of 4-6 year-old school children in Monastir and to investigate the
      association with possible risk factors. METHODS: A descriptive transversal study
      including 121 children aged 4-6 years old (637 males, 698 females), was conducted
      in 10 Kindergartens in Monastir, in 2011. Personal data such as age, sex, birth
      weight, breastfeeding history and parental data including parental weights and
      heights, parental education level and occupation were collected by questionnaires
      completed by parents. Height and weight were measured with a weighing-scale and
      body mass index (BMI; kg/m2) was calculated. The prevalence of overweight and
      obesity was defined based according to the curves of the french reference of
      Rolland Cachera. RESULTS: Prevalence of overweight and obesity was 9.1% and 11.6%
      respectively. Parental factors associated with overweight were: parental obesity:
      44% vs 17% (p=0.005) (OR = 3.65: 1.27-10.57), artificial feeding: 68% vs 33%
      (p=0.0016) (OR= 4.25: 1.51-12.27), and the early diversification of food before
      the age of 6 months: 88% vs 65% (p=0.029) (OR= 3.84: 0.98 - 17.66). Exclusive
      breast feeding duration >= 6mois is probably protector factor against obesity: 0%
      vs 21% (p=0. 01) (OR=0: 0.00 < OR < 0.78). We found no significant difference
      between overweight and non-overweight schoolchildren in frequency of high degree
      educated mother and father, birth weight, breakfast intake, eating habits and
      exercise. However overweight children intake high-caloric food, low in fiber,
      with troubles of nutritional comportment, and a sedentary lifestyle. CONCLUSIONS:
      Risk factors for obesity, well known in most industrialized countries,
      necessitate to be more understood in Tunisia, to place a preventive strategy
      included supervision of children weight, nutritional education and promote
      physical activity and reducing the time spent watching television.

PMID- 22585647
TI  - [Extra-cardiac findings on coronary computed Tomography scanning].
AB  - BACKGROUND: Multi-detector-row computed tomography (MDCT) has emerged as method
      for non-invasive imaging of the heart. AIM: To investigate the frequency of the
      non cardiac findings in cardiac imaging with MDCT. METHODS: A total of 191
      patients underwent cardiac imaging with 64-slice MDCT over a period of 8 months.
      The detected abnormalities were classified in major (implying an immediate workup
      and treatment or at least a further investigation) and minor abnormalities.
      RESULTS: Extra cardiac abnormalities were detected on 69 examinations (36 %).
      Major abnormalities were found in 17 % of the patients, and the minor
      abnormalities in 25,6 %. The scan revealed 4 cases of lung carcinomas, all at a
      still surgical stage. CONCLUSION: There were a significant number of non cardiac
      findings in cardiac MDCT. To avoid missing clinically important findings, we
      should carefully evaluate all the organs included in the scan.

PMID- 22585648
TI  - [Is there a link between the occurrence of Kidney cancer and hypertension in
      Tunisian population?].
AB  - BACKGROUND: Kidney cancer is generally asymptomatic and discovered incidentally
      at a late stage, which is a negative diagnosis because in most cases the disease
      is incurable at this stage. Some predisposing factors have been revealed by
      studies such high blood pressure, which is a frequent among the Tunisian
      population. AIM: A study among the Tunisian population to determine if there is a
      link between the occurrence of kidney cancer and the hypertension. METHODS: Our
      work was conducted on 91 patients with confirmed renal cell carcinoma and 91
      healthy subjects who consulted the Urology Department at the Charles Nicolle
      Hospital in Tunis. The study of clinical records has identified the clinical,
      pathological and therapeutic features of the 182 patients. RESULTS: 59% of
      individuals with hypertension have developed kidney cancer with a significant p
      value equal to 0.03. The more the value of blood pressure increases the more the
      risk is (p = 0.03). Smoking in combination with hypertension is a factor favoring
      the occurrence of cancer with a value of p equal to 0.05. CONCLUSION: In the
      Tunisian population hypertension is a risk factor for developing kidney cancer, a
      factor compounded by the high incidence of this disease. What prompts us to make
      explorations of kidney lodges of hypertensive patients.

PMID- 22585649
TI  - [Lichtenstein versus Lichtenstein plus plug in prosthetic inguinal hernia repair:
      preliminary results of a prospective randomized controlled trial].
AB  - BACKGROUND: Mesh- based hernioplasties became the reference in inguinal hernia
      repair. AIM: To evaluate the results of combining a conic Plug to the
      Lichtenstein Mesh for inguinal hernia repair. METHODS: Between January 2007 and
      January 2009 we included 50 patients with primary or recurrent inguinal hernia in
      a prospective comparative randomized controlled trial. The randomization
      concerned the association of the conic Plug to the Lichtenstein Mesh. The primary
      objectives were to establish if any differences in operation time, postoperative
      pain response and/or postoperative recovery time, chronic pain and recurrence
      could be detected between the 2 groups. All patients were seen and data were
      collected after 2 weeks, 6 months and 2 years. RESULTS: Twenty two patients were
      treated by Lichtenstein Mesh (group A) and we associated the conic Plug to 28
      patients (group B). The mean age was 56 years. Forty three patients were
      discharged after 24 hours. The postoperative pain was low with visual analogue
      scores <= 5 for 48 patients. One patient had residual pain treated efficiency
      with medical treatment. No recurrence in the 2 groups in 2 years outcome. There
      were no significant differences between the 2 groups. CONCLUSION: Results of the
      Lichtenstein plus Plug technique are similar to the Lichtenstein results. There
      were no significant differences between the 2 groups concerning early or late
      complications. The recurrence will be revaluated after 5 and 10 years outcome.

PMID- 22585650
TI  - [Hemolytic and uremic syndrome and sarcoidosis].

PMID- 22585651
TI  - [Huge cervico-facial teratoma].

PMID- 22585652
TI  - [Colorectal cancer in inflammatory bowel diseases].

PMID- 22585653
TI  - Priapism secondary to involvement of corpora cavernosa by locally advanced
      prostate cancer.

PMID- 22585654
TI  - [Unusual cause of hemoptysis].

PMID- 22585655
TI  - Auricular pyoderma gangrenosum associated with Crohn's disease.

PMID- 22585656
TI  - [Neck mass revealing an esopageal duplication cyst].

PMID- 22585657
TI  - [Synchronous rectal adenocarcinoma and duodenal stromal tumor].

PMID- 22585658
TI  - Massive gastrointestinal bleeding caused by small stromal tumour of the jejunum.

PMID- 22585659
TI  - [Serous cystadenoma of the pancreas].

PMID- 22585660
TI  - [Medical treatment of non ruptured interstitial pregnancy].

PMID- 22585661
TI  - Nanog promotes osteogenic differentiation of the mouse mesenchymal cell line
      C3H10T1/2 by modulating bone morphogenetic protein (BMP) signaling.
AB  - How the pluripotency of stem cells is maintained and the role of transcription
      factors in this maintenance remain major questions. In the present study, in
      order to clarify the mechanism underlying the pluripotency of stem cells for the
      advancement of regenerative medicine, we examined the effect of forced Nanog
      expression in mesenchymal cells, with a particular focus on osteogenic
      differentiation. The human mesenchymal stromal cells (hMSCs) or mouse mesenchymal
      cell line C3H10T1/2 cells were transduced with the Nanog gene or control green
      fluorescent protein (GFP) gene by using retrovirus vectors. Short-term, forced
      Nanog gene expression had few effects on the terminal osteogenic differentiation
      of either hMSCs or C3H10T1/2 cells. To determine its long-term effects, we
      established C3H10T1/2 cells expressing Nanog constitutively. Constitutive Nanog
      expression strongly induced osteogenic differentiation of C3H10T1/2 cells. In
      regard to cell proliferation, constitutive Nanog expression only repressed the
      proliferation of the cells treated with rhBMP-2. Moreover, Nanog also had the
      potential to promote the proliferation of C3H10T1/2 cells in the absence of rhBMP
      2. Constitutive Nanog expression enhanced phosphorylation of Smad1/5/8 and
      suppressed Cdk4 and cyclinD1. The promoter activities of both the osteocalcin and
      Id-1 genes were activated in cells expressing Nanog constitutively. To identify
      downstream molecules of Nanog involved in the promotion of osteogenic
      differentiation, we performed a DNA microarray analysis and discovered that
      NFATc1 was one of the downstream effectors of Nanog. These results indicate that
      Nanog functions as a modulator of BMP signaling in C3H10T1/2 cells probably
      through a genome reprogramming process.

PMID- 22585662
TI  - Deletion of the ST2 proximal promoter disrupts fibroblast-specific expression but
      does not reduce the amount of soluble ST2 in circulation.
AB  - IL-33 signals through ST2, which is expressed either as a full-length signaling
      receptor or a truncated soluble receptor that can suppress IL-33 activity.
      Previous data suggest that soluble ST2 mRNA in fibroblasts is coupled to a serum
      inducible proximal promoter, while full-length ST2 expression in immune cells is
      directed from a distal promoter. In order to better understand the function of
      the alternative promoters and how they ultimately affect the regulation of IL-33,
      we generated a mouse in which the ST2 proximal promoter is deleted. Promoter
      deletion had no impact on ST2 expression in mast cells or their ability to
      respond to IL-33. In contrast, it resulted in a complete loss of both soluble and
      full-length ST2 mRNA in fibroblasts, which corresponded with both an inability to
      secrete soluble ST2 and a defect in IL-33 responsiveness. Importantly, in spite
      of the fibroblast defect, soluble ST2 concentrations were not reduced in the
      serum of naive or allergen-exposed knockout mice. In summary, we found that ST2
      promoter usage is largely cell-type dependent but does not dictate splicing.
      Moreover, the proximal promoter is not a major driver of circulating soluble ST2
      under the conditions tested.

PMID- 22585663
TI  - Pneumopericardium diagnosis by point-of-care ultrasonography.
AB  - Focused cardiac ultrasound by the emergency physician has become a fundamental
      tool to expedite the diagnostic evaluation of the patient at bedside. We report
      the case of a patient admitted to the emergency department for respiratory
      distress. He was examined by an emergency physician who performed a bedside
      echocardiography. Bright spots were seen rapidly moving along the pericardial
      layer during diastole with comet-tail artifacts extending across the whole image
      of the heart and disappearing during systole, suggesting pneumopericardium.

PMID- 22585664
TI  - The impact of acute illness on HbA(1c)  determination of undiagnosed diabetes.
AB  - OBJECTIVE: To improve diabetes screening efforts, the American Diabetes
      Association now recommends haemoglobin A(1c) (HbA(1c)) as a diagnostic test,
      increasing access to patients found in acute care environments. However, the
      influence of acute illness and care on HbA(1c) levels has not been well studied.
      To address this, we evaluated for intra-patient differences in HbA(1c) assessed
      in the emergency department (ED) and after recovery from the acute illness.
      METHODS: Adult patients with no known history of diabetes were tested for HbA(1c)
      during an ED and scheduled follow-up visit. HbA(1c) differences between the two
      visits were compared using limits of agreement with 95% confidence intervals. The
      frequency of individuals who changed diagnostic categories (using >=6.5% to
      classify newly diagnosed diabetes) from ED to follow-up was determined. RESULTS:
      A total of 589 patients were included with a mean age of 50 years, and 57/589
      (9.7%) had an ED HbA(1c)  >= 6.5% with the average follow-up visit 45 days after
      the ED visit. The mean ED HbA(1c) was 5.67% (+/-0.86), and the follow-up HbA(1c)
      was 5.65% (+/-0.89), (difference -0.0129%, 95% limits of agreement -0.740,
      0.714). The ED and follow-up HbA(1c) was highly correlated (r2 = 0.829). Although
      on follow-up almost all patients were classified in the same diagnostic category
      as in the ED, 17 patients had an HbA(1c)  >= 6.5% in the ED and an HbA(1c)  <
      6.5%. On follow-up most patients (14/17) still fell in an abnormal range (6.0
      6.5%). CONCLUSION: The HbA(1c) value is not substantially affected by acute
      illness and is feasible as a screening assay for diabetes in the acute care
      setting such as an ED.

PMID- 22585665
TI  - Growth hormone secretion and its effect on height in pediatric patients with
      different genotypes of Prader-Willi syndrome.
AB  - There have been multiple reports regarding the growth hormone (GH) secretion in
      patients with Prader-Willi syndrome (PWS). However, none have compared GH
      secretion in children with deletion group to those with maternal uniparental
      disomy (UPD). We evaluated the GH secretion in pediatric patients with PWS.
      Seventy-six patients with a deletion (n = 55) or UPD (n = 21) were studied. The
      secretion of GH by insulin stimulation in the patients with UPD (3.6 +/- 2.2
      ng/ml) was significantly lower than those with deletions (peak GH level: 11.1 +/-
      8.6 ng/ml; P = 0.0013). We also compared the response to GH replacement therapy.
      Yearly improvements in height standard deviation score (SDS) were similar in the
      two groups (first year SDS: 0.47 +/- 0.47, deletion; 0.68 +/- 0.26, UPD; P =
      0.14).

PMID- 22585666
TI  - Is the addition of the ductus venosus useful when screening for aneuploidy and
      congenital heart disease in fetuses with normal nuchal translucency?
AB  - OBJECTIVE: The aim of this study was to examine the possible role of Doppler
      ultrasound assessment of ductus venosus (DV) blood flow at 11+0-13+6 weeks'
      gestation in fetuses with normal nuchal translucency (NT) in screening for
      autosomal trisomies (AT) and for congenital heart diseases (CHD) in chromosomally
      normal fetuses. METHODS: First-trimester combined screening for trisomy 21 (T21)
      was carried out prospectively for 7 years in singleton pregnancies. NT and the
      pulsatility index for DV (DVPI) were calculated. The DV was analyzed according to
      its association with AT and CHD. The detection rate (DR), false-positive rate
      (FPR), positive predictive value (PPV), and odds ratio (OR) for abnormal DV were
      calculated. RESULTS: Abnormal DV as an early marker of euploid CHD gives a DR of
      12.5%, an FPR of 4.3%, a PPV of 1.4%, and a negative predictive value (NPV) of
      99.5%, with an OR of 3.1 (95% CI 1.3-7.4). Moreover, abnormal DV as an early
      marker of AT shows a DR of 35.7%, an FPR of 4.3%, a PPV of 1.2%, an NPV of 99.9%,
      and an OR of 12.3 (95% CI 4.1-36), and the values are 33.3, 4.3, 0.97, and 99.9%
      and 11 (95% CI 3.2-36.9), respectively, for T21. CONCLUSIONS: Our data supports
      the association between increased DVPI and CHD or AT. The sensitivity of this
      marker is not strong enough to be used a screening test.

PMID- 22585668
TI  - Retracted article: Running like Alice and losing good ideas: on the quasi
      compulsive use of English by non-native English speaking scientists.

PMID- 22585667
TI  - Atypically located pericardial cyst compressing the left ventricle during the
      whole cardiac cycle: a case report.
AB  - We report the uncommon case of a pericardial cyst with unremitting compression of
      the left ventricle during the whole cardiac cycle, but normal ejection fraction.
      On CT scan, the cyst was found at an atypical location, lateral to the pulmonary
      artery, the ascending aorta, and the right ventricular outflow tract in the left
      anterior mediastinum. The radio-density of the cyst was 41 Hounsfield units (HU),
      higher than other cases reported in the literature. As the cyst was stable,
      conservative treatment was adopted. The usefulness of echocardiography for the
      diagnosis and follow-up of pericardial cysts is discussed.

PMID- 22585669
TI  - Beta blocker use and colorectal cancer risk: population-based case-control study.
AB  - BACKGROUND: Recently, it has been postulated that long-term use of beta blockers
      might decrease the risk of certain types of cancer because of weakening of
      norepinephrine signaling. Previous studies on colorectal cancer (CRC) yielded
      inconsistent results, but lacked information on covariates. Thus, the authors
      investigated the association of beta blocker use and CRC risk in a large
      population-based case-control study (DACHS study). METHODS: Between 2003 and
      2007, information on beta blocker use and potential confounders was collected by
      personal interviews for 1762 CRC cases and 1708 control individuals from Germany.
      The association of CRC risk and beta blocker use and subclasses of beta blockers
      was estimated by multiple logistic regression. In addition, site- and stage
      specific analyses were performed. RESULTS: After adjustment for covariates, no
      association was observed with beta blocker use (odds ratio [OR], 1.05; 95%
      confidence interval [CI], 0.86-1.29) or with duration of beta blocker use. Also,
      the analysis by subclasses of beta blockers (cardioselectivity) and active
      ingredients (metoprolol, bisoprolol, carvedilol, and atenolol) or by CRC subsite
      showed no associations. In stage-specific analyses, long-term beta blocker use
      (6+ years) was associated with a significantly higher risk of stage IV CRC (OR,
      2.02; 95% CI, 1.25-3.27). CONCLUSIONS: Our adjusted results do not support the
      hypothesis that beta blocker use is associated with decreased risk of CRC. In
      contrast, we found a positive association of long-term beta blocker use and risk
      of stage IV CRC. The latter result should be further evaluated in future studies.

PMID- 22585670
TI  - Prostaglandin F2alpha: a bone remodeling mediator.
AB  - Prostaglandin F2alpha (PGF2alpha) plays multiple roles on bone metabolism by
      regulating a wide range of signaling pathways. PGF2alpha, via activation of PKC,
      stimulates Na-dependent inorganic phosphate (Pi) transport system in osteoblasts;
      up-regulates interleukin (IL)-6 synthesis; increases vascular endothelial growth
      factor (VEGF). In addition, PGF2alpha acts as a strong mitogenic and survival
      agent on osteoblasts, and these effects are, at least in part, mediated by the
      binding of fibroblast growth factor-2 (FGF-2) to the specific receptor FGFR1. The
      understanding of PGF2alpha intracellular network, albeit complex to clarify,
      provides molecular bases useful to identify the players of osteoblast
      proliferation, apoptosis, and the associated angiogenic processes. Indeed, the
      molecular mechanism that underline PGF2alpha-regulated bone metabolism may be a
      promising platform for the development of novel targeted therapies in the
      treatment of bone disorders and disease.

PMID- 22585671
TI  - Intra-islet proliferation of cytotoxic T lymphocytes contributes to insulitis
      progression.
AB  - Infiltration of pancreatic islets by immune cells, termed insulitis, increases
      progressively once it begins and leads to clinical type 1 diabetes. But even
      after diagnosis some islets remain unaffected and infiltration is patchy rather
      than uniform. Traffic of autoreactive T cells into the pancreas is likely to
      contribute to insulitis progression but it could also depend on T-cell
      proliferation within islets. This study utilizes transgenic NOD mice to assess
      the relative contributions of these two mechanisms. Progression of insulitis in
      NOD8.3 TCR transgenic mice was mildly reduced by inhibition of T-cell migration
      with the drug FTY720. In FTY720-treated mice, reduced beta cell MHC class I
      expression prevented progression of insulitis both within affected islets and to
      previously unaffected islets. CTL proliferation was significantly reduced in
      islets with reduced or absent beta cell expression of MHC class I protein. This
      indicates that intra-islet proliferation, apparently dependent on beta cell
      antigen presentation, in addition to recruitment, is a significant factor in
      progression of insulitis.

PMID- 22585672
TI  - Bridging the gap between problem recognition and treatment: the use of proactive
      work behaviors by experienced critical care nurses.
AB  - Delayed access to physicians has been identified as a factor in preventable
      adverse patient events during hospitalization. Nurses as front-line providers are
      well positioned to provide a timely response to the needs of patients. Yet legal
      regulations and hospital policies limit the actions nurses can initiate without
      physician authorization. The purpose of this qualitative study was to describe
      what experienced critical care nurses do when they recognize a problem that
      warrants treatment but lack physician authorization to intervene. The 13 nurses
      who participated in this study bridged the gap between problem recognition and
      treatment by communicating proactively, being persistent, running interference
      for other nurses, and, in some situations, acting without physician
      authorization. Revising legal regulations and hospital policies to incorporate
      greater acknowledgment of the overlapping functions between medicine and nursing
      and recognition of the knowledge and expertise of experienced nurses may be
      important in reducing unnecessary treatment delays during hospitalization.

PMID- 22585673
TI  - Risk factors for low birth weight in New York state counties.
AB  - The rate of low birth weight (LBW) is a national concern. In New York counties in
      2009, the LBW rate was 8.2%. Reducing LBW has significant humanitarian and
      economic implications. At an average cost of $51,600 per infant, care for infants
      weighing less than 2,500 grams at birth is substantial. The purpose of this study
      was to identify demographic, socioeconomic, and health service factors that
      contribute to LBW among counties in New York. Analyses of data indicated that the
      number of MOMs providers and teen pregnancy rate were the strongest predictors
      for LBW. These findings reinforce the fact that LBW is a correctable phenomenon
      that can be addressed through public policy. With increasing budget cuts,
      provision of health services and implementation of programs that address teen
      pregnancy have become challenging. Public policy decisions and stewardship that
      support programs that increase the number of providers for the uninsured,
      underinsured, and economic underclass and maintain programs for the pregnant
      adolescent will help New York counties in their fight against LBW.

PMID- 22585674
TI  - Defining a functionally distinct subset of human memory CD4+ T cells that are
      CD25POS and FOXP3NEG.
AB  - Surface expression of the IL-2 receptor alpha-chain (CD25) has been used to
      discriminate between CD4(+) CD25(HI) FOXP3(+)  regulatory T (Treg) cells and
      CD4(+) CD25(NEG) FOXP3(-)  non-Treg cells. However, this study reports that the
      majority of resting human memory CD4(+) FOXP3(-)  T cells expresses intermediate
      levels of CD25 and that CD25 expression can be used to delineate a functionally
      distinct memory subpopulation. The CD25(NEG)  memory T-cell population contains
      the vast majority of late differentiated cells that respond to antigens
      associated with chronic immune responses and are increased in patients with
      systemic lupus erythematosus (SLE). In contrast, the CD25(INT)  memory T cells
      respond to antigens associated with recall responses, produce a greater array of
      cytokines, and are less dependent on costimulation for effector responses due to
      their expression of CD25. Lastly, compared to the CD25(NEG)  and Treg-cell
      populations, the CD25(INT)  memory population is lost to a greater degree from
      the blood of cancer patients treated with IL-2. Collectively, these results show
      that in humans, a large proportion of CD4(+)  memory T cells express intermediate
      levels of CD25, and this CD25(INT) FOXP3(-)  subset is a functionally distinct
      memory population that is uniquely affected by IL-2.

PMID- 22585675
TI  - Secondary head and neck cancer in patients with history of hematological
      malignancy.
AB  - BACKGROUND: Head and neck cancer is a common second cancer in patients with a
      history of hematological malignancies. The purpose of this study was present the
      clinical characteristics and treatment outcomes of this group of patients.
      METHODS: A retrospective analysis was conducted of all patients who had a history
      of hematological malignancy and developed head and neck cancer in a 10-year
      period. RESULTS: The cohort had 10 patients; median age was 45.8 years. Most
      patients were nonsmokers and nondrinkers. Seven patients had chronic graft-versus
      host disease. The median interval between the completion of treatment of
      hematological malignancy and the development of head and neck cancers was 8.79
      years (range, 2.33-26.83 years). Six patients were alive and disease-free, 3
      developed local recurrence, and 3 had metachronous head and neck cancers.
      CONCLUSION: The risk factors and etiology of head and neck cancers in patients
      with hematological malignancy may be different from the ordinary population.

PMID- 22585676
TI  - Autophagy and ionizing radiation in tumors: the "survive or not survive" dilemma.
AB  - Autophagy is a so-called "self-eating" system responsible for degrading long
      lived proteins and cytoplasmic organelles, whose products are recycled to
      maintain cellular homeostasis. This ability makes autophagy a good candidate for
      a survival mechanism in response to several stresses, including the tumor cell
      transformation. In particular, recent studies suggested that autophagy functions
      as a pro-death mechanism within different tumor contexts. It is, however, widely
      reported that autophagy represents both a survival mechanism or contributes
      directly to cell death fate. This interplay of the autophagy functions has been
      observed in many types of cancers and, in some cases, autophagy has been
      demonstrated to both promote and inhibit antitumor drug resistance. From a
      therapeutical point of view, the effects of the modulation of the tumor cell
      autophagic status, in response to ionizing radiations, are presently of
      particular relevance in oncology. Accordingly, this review also provides a
      perspective view on future works for exploring the modulation of autophagic
      indices in tumor cells as a novel molecular-based adjuvant strategy, in order to
      improve radiotherapy and chemotherapy effects in cancer patients.

PMID- 22585677
TI  - Network for Pancreatic Organ Donors with Diabetes (nPOD): developing a tissue
      biobank for type 1 diabetes.
AB  - BACKGROUND: The Network for Pancreatic Organ Donors with Diabetes (nPOD) was
      established to recover and characterize pancreata and related organs from
      cadaveric organ donors with various risk levels for type 1 diabetes (T1D). These
      biospecimens are available to investigators for collaborative studies aimed at
      addressing questions related to T1D natural history and pathogenesis. RESEARCH
      DESIGN AND METHODS: Organ donors included T1D patients (new onset to long term),
      non-diabetic autoantibody-positive subjects, non-diabetic controls and
      individuals with disorders relevant to beta-cell function. Pancreas recovery and
      transport met transplant-grade criteria. Additional samples recovered included
      serum, whole blood, spleen and pancreatic and non-pancreatic lymph nodes.
      Biospecimens were processed for cryopreserved cells, fixed paraffin and fresh
      frozen blocks and snap frozen samples. T1D autoantibodies, C-peptide levels and
      high-resolution HLA genotyping for risk alleles were also determined. RESULTS:
      Over 160 donors have been enrolled (ages of 1 day to >90 years). Standard
      operating procedures were established along with a quality management system.
      Donor demographics, laboratory assays and histopathological characterizations
      were shared through an open online informatics system. Biospecimens were
      distributed to more than 60 investigators. CONCLUSIONS: The nPOD programme
      provides access to high quality biospecimens without cost to investigators.
      Collaborations and open data sharing are emphasized to maximize research
      potential of each donor. On the basis of initial successes, the nPOD programme is
      expanding to recover additional organs relevant to T1D pathogenesis and
      complications from European countries (PanFin network).

PMID- 22585678
TI  - Sonography of the adrenal glands in the adult.
AB  - Although its capability has been overlooked, sonography can be a useful screening
      tool for adrenal lesion in adults. In this article, we discuss scan technique,
      patient positioning, and anatomic consideration for adrenal sonography in adults
      and illustrate sonographic appearance of normal adrenal gland as well as adrenal
      tumors and tumor-like lesions.

PMID- 22585679
TI  - Age-dependent differences in morphine-induced taste aversions.
AB  - Adolescence is a developmental period of particular importance given the host of
      neurobiological changes that occur during this stage of development. Drug use and
      abuse is said to be a function of the balance of its rewarding and aversive
      effects, and any age-dependent differences in morphine's aversive effects could
      impact drug intake. The present experiments examined the ability of morphine
      sulfate (0, 3.2, 10, and 18 mg/kg) to induce taste aversions in adolescent and
      adult rats under high (20-min fluid access each day; Experiment 1A/B) and low
      (50% of ad libitum access; Experiment 2A/B) deprivation conditions. In both
      studies, adolescent and adult rats were given a novel saccharin solution to drink
      and were subsequently injected with morphine. Independent of the deprivation
      condition, adults acquired stronger aversions than adolescents and did so at a
      faster rate. On a subsequent two-bottle aversion test, all morphine-injected
      subjects drank a significantly lower percentage of saccharin than vehicle
      injected controls with adults exhibiting stronger aversions than adolescents.
      These age-dependent differences in morphine-induced CTAs extend the findings with
      other drugs of abuse for which adolescents exhibit weaker aversions. The possible
      basis for and implications of these differences were discussed.

PMID- 22585680
TI  - Giant cavernous mesenteric lymphangioma in adult.

PMID- 22585681
TI  - AP-1 is involved in ICOS gene expression downstream of TCR/CD28 and cytokine
      receptor signaling.
AB  - It has been proposed that sustained ICOS expression in chronic inflammatory
      immune conditions, such as autoimmunity and allergy, contributes to symptom
      exacerbation. Therefore modulation of ICOS gene expression could be a potential
      therapeutic strategy for such immune diseases. However, the precise molecular
      mechanisms controlling ICOS gene expression remain poorly understood. In this
      study, we explored transcription factors involving in ICOS gene expression and
      examined their roles in a physiological situation. Microarray analysis revealed
      that one AP-1 molecule, Fos-related antigen-2 (Fra2), was highly correlated with
      ICOS expression. Ectopic expression of Fra2 and other AP-1 molecules upregulated
      ICOS expression on T cells. We identified an AP-1-responsive site (AP1-RE) within
      the ICOS promoter region and demonstrated AP-1 actually binds to AP1-RE upon
      TCR/CD28 stimulation. Meanwhile, we found several cytokines could upregulate ICOS
      expression on both naive and effector T cells in a manner independent of TCR/CD28
      stimulation. These cytokine stimuli induced AP-1 binding to AP1-RE. Together, our
      results indicate AP-1 transcription factors are involved in ICOS gene expression
      downstream of both TCR/CD28 signaling and cytokine receptor signaling, and
      suggest AP-1 activation via cytokine receptor signaling may be one of the
      mechanisms maintaining high level ICOS expression in chronic inflammatory immune
      responses.

PMID- 22585682
TI  - NK cells are strongly activated by Lassa and Mopeia virus-infected human
      macrophages in vitro but do not mediate virus suppression.
AB  - Lassa virus (LASV) and Mopeia virus (MOPV) are closely related Arenaviruses. LASV
      causes hemorrhagic fever, whereas MOPV is not pathogenic. Both viruses display
      tropism for APCs such as DCs and macrophages. During viral infections, NK cells
      are involved in the clearance of infected cells and promote optimal immune
      responses by interacting with APCs. We used an in vitro model of human NK and APC
      coculture to study the role of NK cells and to characterize their interactions
      with APCs during LASV and MOPV infections. As expected, NK cells alone were
      neither infected nor activated by LASV and MOPV, and infected DCs did not
      activate NK cells. By contrast, LASV- and MOPV-infected macrophages activated NK
      cells, as shown by the upregulation of CD69, NKp30, and NKp44, the downregulation
      of CXCR3, and an increase in NK-cell proliferation. NK cells acquired enhanced
      cytotoxicity, as illustrated by the increase in granzyme B (GrzB) expression and
      killing of K562 targets, but did not produce IFN-gamma. Contact between NK cells
      and infected macrophages and type I IFNs were essential for activation; however,
      NK cells could not kill infected cells and control infection. Overall, these
      findings show that MOPV- as well as pathogenic LASV-infected macrophages mediate
      NK-cell activation.

PMID- 22585683
TI  - Mucin as a therapeutic target in pseudomyxoma peritonei.
AB  - Pseudomyxoma peritonei (PMP) is characterized by intraperitoneal dissemination of
      mucinous ascites. This malignancy frequently recurs despite aggressive
      locoregional therapies, demonstrates chemo-insensitivity and lacks targeted
      therapies. This review addresses some intriguing questions in PMP; what role does
      mucin play in this malignancy?; what genetic alterations and dysregulated
      signaling pathways lead to a putative goblet cell-lineage differentiation or
      mucin overexpression?; are targeted therapies against known transcriptional
      pathways for mucin production a novel therapeutic strategy in this malignancy?

PMID- 22585684
TI  - Melanoma cells become resistant to NK-cell-mediated killing when exposed to NK
      cell numbers compatible with NK-cell infiltration in the tumor.
AB  - During the past few years, a number of studies reported that different melanoma
      cell lines could be extensively lysed in vitro by IL-2-activated NK cells at
      appropriate effector/target ratios. Here, we show, by histological evaluation of
      different melanoma lesions, that NK/target-cell ratios compatible with those
      allowing efficient melanoma cell killing in vitro are hardly reached at the tumor
      site. We then investigated the outcome of cocultures established at low
      NK/melanoma cell ratios. After initial NK-mediated lysis, residual melanoma cells
      acquired resistance to IL-2-activated NK cells. This reflected primarily an
      increased expression, on melanoma cells, of classical and nonclassical HLA class
      I molecules, accompanied by a partial downregulation of NKG2D-ligands, and was
      dependent on NK-mediated IFN-gamma release. Consistently, melanoma lesions showed
      a higher HLA class I expression on tumor cells that were proximal to infiltrating
      NK cells. In long-term cocultures, the "protective phenotype" acquired by
      melanoma cells was lost over time. However, this phenomenon was counteracted by
      downregulation of relevant activating receptors in cocultured NK cells. Analysis
      of different NK-cell-activating cytokines indicated that IL-15 can partially
      overcome this novel tumor escape mechanism suggesting that IL-15, rather than IL
      2, may be eligible for NK-cell-based immunotherapy.

PMID- 22585685
TI  - The era of combination therapy in myeloma.

PMID- 22585686
TI  - Are medicare-based findings applicable to all prostatectomy patients?

PMID- 22585687
TI  - Prospective study of falls and risk factors for falls in adults with advanced
      cancer.
AB  - PURPOSE: Retrospective studies of inpatients with cancer suggest that a cancer
      diagnosis confers a high risk of falls. In adults with advanced cancer, we aimed
      to prospectively document the incidence of falls, identify the risk factors, and
      determine if falls in this population occur predominantly in older patients.
      PATIENTS AND METHODS: Patients admitted consecutively to community and inpatient
      palliative care services with metastatic or locoregionally advanced cancer who
      were mobile without assistance were recruited. Risk-factor assessment was
      conducted on initial encounter. Patients underwent follow-up via weekly telephone
      contact for 6 months or until time of fall or death. Relationship between
      covariates and time to fall was examined using hazard ratios (HRs) derived from
      univariate and multivariate Cox proportional hazards models. RESULTS: Of 185
      participants (52.4% men; mean age 68 +/- standard deviation of 12.6 years), 50.3%
      fell; 35 (53%) of 66 participants age < 65 years and 58 (48.7%) of 119 age >= 65
      years fell; 61.3% of falls occurred in the community; 42% resulted in injury.
      Median time to fall was 96 days (95% CI, 64.66 to 127.34). Primary brain tumor or
      brain metastasis (HR 2.5; P = .002), number of falls in the preceding 3 months
      (HR, 1.27; P = .005), severity of depression (HR, 1.12; P = .012), benzodiazepine
      dose (HR, 1.05; P = .004), and cancer-related pain (HR, 1.96; P = .024) were
      independently associated with time to fall in multivariate analysis. CONCLUSION:
      Fifty percent of adults with advanced cancer, regardless of age, will experience
      a fall associated with high risk of physical injury. There is a compelling need
      to assess the efficacy of assessment and management of modifiable fall risk
      factors in patients with advanced cancer.

PMID- 22585688
TI  - Metastatic prostate adenocarcinoma diagnosed in a colonic polyp.

PMID- 22585689
TI  - Intracutaneous and intravesical immunotherapy with keyhole limpet hemocyanin
      compared with intravesical mitomycin in patients with non-muscle-invasive bladder
      cancer: results from a prospective randomized phase III trial.
AB  - PURPOSE: Despite current treatment after transurethral resection of a bladder
      tumor, recurrences and progression remain a problem. Keyhole limpet hemocyanin
      (KLH) was beneficial in earlier studies. In this study, safety and efficacy of
      KLH were compared with that of mitomycin (MM). PATIENTS AND METHODS: Patients
      with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC)
      without carcinoma in situ were enrolled in a randomized phase III trial. In all,
      283 patients were randomly assigned for 16 adjuvant intravesical instillations
      with KLH after preimmunization, and 270 patients were randomly assigned for 11
      adjuvant intravesical instillations with MM. Primary outcome measurement was
      recurrence-free survival (RFS). Secondary outcome measurements were progression
      free survival, adverse events (AEs), and the effect of delayed-type
      hypersensitivity (DTH) response on clinical outcome. RESULTS: There were
      significantly more pT1 tumors in the MM group (P = .01). In a log-rank test,
      univariate and multivariate Cox regression analysis, KLH was less effective than
      MM regarding RFS (all P < .001). Progression was uncommon (n = 20). In univariate
      Cox regression analyses, KLH tended to prevent progression more effectively than
      MM, but in multivariate Cox regression analyses, this could not be shown. AEs
      were common but mild. Fever, flu-like symptoms, and fatigue occurred
      significantly more after KLH treatment. Allergic reactions and other skin
      disorders occurred significantly more after MM treatment. Significantly more DTH
      positive patients developed a recurrence than DTH-negative patients. CONCLUSION:
      KLH had a different safety profile and was inferior to MM in preventing NMIBC
      recurrences. KLH tended to be more effective than MM in preventing progression.
      More research is needed to clarify the immunologic effects of KLH and the effects
      of KLH on progression.

PMID- 22585690
TI  - Adjuvant therapy for gastric cancer: revisiting the past to clarify the future.

PMID- 22585692
TI  - Superiority of the triple combination of bortezomib-thalidomide-dexamethasone
      over the dual combination of thalidomide-dexamethasone in patients with multiple
      myeloma progressing or relapsing after autologous transplantation: the MMVAR/IFM
      2005-04 Randomized Phase III Trial from the Chronic Leukemia Working Party of the
      European Group for Blood and Marrow Transplantation.
AB  - PURPOSE: This prospective multicenter phase III study compared the efficacy and
      safety of a triple combination (bortezomib-thalidomide-dexamethasone [VTD])
      versus a dual combination (thalidomide-dexamethasone [TD]) in patients with
      multiple myeloma (MM) progressing or relapsing after autologous stem-cell
      transplantation (ASCT). PATIENTS AND METHODS: Overall, 269 patients were randomly
      assigned to receive bortezomib (1.3 mg/m(2) intravenous bolus) or no bortezomib
      for 1 year, in combination with thalidomide (200 mg per day orally) and
      dexamethasone (40 mg orally once a day on 4 days once every 3 weeks). Bortezomib
      was administered on days 1, 4, 8, and 11 with a 10-day rest period (day 12 to day
      21) for eight cycles (6 months), and then on days 1, 8, 15, and 22 with a 20-day
      rest period (day 23 to day 42) for four cycles (6 months). RESULTS: Median time
      to progression (primary end point) was significantly longer with VTD than TD
      (19.5 v13.8 months; hazard ratio, 0.59; 95% CI, 0.44 to 0.80; P = .001), the
      complete response plus near-complete response rate was higher (45% v 21%; P
      0.001), and the median duration of response was longer (17.9 v 13.4 months; P.04)
      [corrected].The 24-month survival rate was in favor of VTD (71% v 65%; P = .093).
      Grade 3 peripheral neuropathy was more frequent with VTD (29% v 12%; P = .001) as
      were the rates of grades 3 and 4 infection and thrombocytopenia. CONCLUSION: VTD
      was more effective than TD in the treatment of patients with MM with progressive
      or relapsing disease post-ASCT but was associated with a higher incidence of
      grade 3 neurotoxicity.

PMID- 22585691
TI  - Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of
      adjuvant radiochemotherapy versus observation after curative gastric cancer
      resection.
AB  - PURPOSE: Surgical resection of gastric cancer has produced suboptimal survival
      despite multiple randomized trials that used postoperative chemotherapy or more
      aggressive surgical procedures. We performed a randomized phase III trial of
      postoperative radiochemotherapy in those at moderate risk of locoregional failure
      (LRF) following surgery. We originally reported results with 4-year median follow
      up. This update, with a more than 10-year median follow-up, presents data on
      failure patterns and second malignancies and explores selected subset analyses.
      PATIENTS AND METHODS: In all, 559 patients with primaries >= T3 and/or node
      positive gastric cancer were randomly assigned to observation versus
      radiochemotherapy after R0 resection. Fluorouracil and leucovorin were
      administered before, during, and after radiotherapy. Radiotherapy was given to
      all LRF sites to a dose of 45 Gy. RESULTS: Overall survival (OS) and relapse-free
      survival (RFS) data demonstrate continued strong benefit from postoperative
      radiochemotherapy. The hazard ratio (HR) for OS is 1.32 (95% CI, 1.10 to 1.60; P
      = .0046). The HR for RFS is 1.51 (95% CI, 1.25 to 1.83; P < .001). Adjuvant
      radiochemotherapy produced substantial reduction in both overall relapse and
      locoregional relapse. Second malignancies were observed in 21 patients with
      radiotherapy versus eight with observation (P = .21). Subset analyses show robust
      treatment benefit in most subsets, with the exception of patients with diffuse
      histology who exhibited minimal nonsignificant treatment effect. CONCLUSION:
      Intergroup 0116 (INT-0116) demonstrates strong persistent benefit from adjuvant
      radiochemotherapy. Toxicities, including second malignancies, appear acceptable,
      given the magnitude of RFS and OS improvement. LRF reduction may account for the
      majority of overall relapse reduction. Adjuvant radiochemotherapy remains a
      rational standard therapy for curatively resected gastric cancer with primaries
      T3 or greater and/or positive nodes.

PMID- 22585693
TI  - Cytogenetics, not just previous therapy, determines the course of therapy-related
      myeloid neoplasms.

PMID- 22585695
TI  - Sex differences in fertility-related information received by young adult cancer
      survivors.
AB  - PURPOSE: The aim was to investigate male and female cancer survivors' perception
      of fertility-related information and use of fertility preservation (FP) in
      connection with cancer treatment during reproductive age. METHODS: The study
      sample consisted of cancer survivors diagnosed from 2003 to 2007 identified in
      population-based registers in Sweden. Inclusion criteria included survivors who
      were age 18 to 45 years at diagnosis and had lymphoma, acute leukemia, testicular
      cancer, ovarian cancer, or female breast cancer treated with chemotherapy. Of 810
      eligible participants, 484 survivors (60% response rate) completed a postal
      questionnaire. RESULTS: The majority of male participants reported having
      received information about treatment impact on fertility (80%) and FP (68%), and
      more than half of the men banked frozen sperm (54%). Among women, less than half
      (48%) reported that they received information about treatment impact on
      fertility, and 14% reported that they received information about FP. Only seven
      women (2%) underwent FP. Predictors for receiving information about treatment
      impact on fertility were a pretreatment desire to have children (odds ratio [OR],
      3.5), male sex (OR, 3.2), and being <= 35 years of age at diagnosis (OR, 2.0).
      Predictors for receiving information about FP included male sex (OR, 14.4), age
      <= 35 at diagnosis (OR, 5.1), and having no children at diagnosis (OR, 2.5).
      CONCLUSION: Our results show marked sex differences regarding the receipt of
      fertility-related information and use of FP. There is an urgent need to develop
      fertility-related information adapted to female patients with cancer to improve
      their opportunities to participate in informed decisions regarding their
      treatment and future reproductive ability.

PMID- 22585694
TI  - Influence of sex on the survival of patients with esophageal cancer.
AB  - PURPOSE: The prognostic value of sex for esophageal cancer survival is currently
      unclear, and growing data suggest that hormonal influences may account for
      incidence disparities between men and women. Therefore, moving from the
      hypothesis that hormones could affect the prognosis of patients with esophageal
      cancer, we investigated the primary hypothesis that sex is associated with
      survival and the secondary hypotheses that the relationship between sex and
      survival depends, at least in part, on age, histology, and race/ethnicity.
      PATIENTS AND METHODS: By using the SEER databases from 1973 to 2007, we
      identified 13,603 patients (34%) with metastatic esophageal cancer (MEC) and
      26,848 patients (66%) with locoregional esophageal cancer (LEC). Cox proportional
      hazards model for competing risks were used for analyses. RESULTS: In the
      multivariate analysis, women had longer esophageal cancer-specific survival
      (ECSS) than men in both MEC (hazard ratio [HR], 0.949; 95% CI, 0.905 to 0.995; P
      = .029) and LEC (HR, 0.920; 95% CI, 0.886 to 0.955; P < .001) cohorts. When age
      and histology were accounted for, there was no difference for ECSS between men
      and women with adenocarcinoma. In contrast, women younger than age 55 years (HR,
      0.896; 95% CI, 0.792 to 1.014; P = .081) and those age 55 years or older (HR,
      0.905; 95% CI, 0.862 to 0.950; P < .001) with squamous cell LEC had longer ECSS
      than men. In the squamous cell MEC cohort, only women younger than age 55 years
      had longer ECSS (HR, 0.823; 95% CI, 0.708 to 0.957; P = .011) than men.
      CONCLUSION: Sex is an independent prognostic factor for patients with LEC or MEC.
      As secondary hypotheses, in comparison with men, women age 55 years or older with
      squamous cell LEC and women younger than age 55 years with squamous cell MEC have
      a significantly better outcome. These last two findings need further validation.

PMID- 22585696
TI  - Phase II trial of vorinostat with idarubicin and cytarabine for patients with
      newly diagnosed acute myelogenous leukemia or myelodysplastic syndrome.
AB  - PURPOSE: To evaluate the safety and efficacy of the combination of the histone
      deacetylase inhibitor vorinostat with idarubicin and ara-C (cytarabine) in
      patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS).
      PATIENTS AND METHODS: Patients with previously untreated AML or higher-risk MDS
      age 15 to 65 years with appropriate organ function and no core-binding factor
      abnormality were candidates. Induction therapy was vorinostat 500 mg orally three
      times a day (days 1 to 3), idarubin 12 mg/m(2) intravenously (IV) daily * 3 (days
      4 to 6), and cytarabine 1.5 g/m(2) IV as a continuous infusion daily for 3 or 4
      days (days 4 to 7). Patients in remission could be treated with five cycles of
      consolidation therapy and up to 12 months of maintenance therapy with single
      agent vorinostat. The study was designed to stop early if either excess toxicity
      or low probability of median event-free survival (EFS) of more than 28 weeks was
      likely. RESULTS: After a three-patient run-in phase, 75 patients were treated.
      Median age was 52 years (range, 19 to 65 years), 29 patients (39%) were
      cytogenetically normal, and 11 (15%) had FLT-3 internal tandem duplication (ITD).
      No excess vorinostat-related toxicity was observed. Induction mortality was 4%.
      EFS was 47 weeks (range, 3 to 134 weeks), and overall survival was 82 weeks
      (range, 3 to 134 weeks). Overall response rate (ORR) was 85%, including 76%
      complete response (CR) and 9% in CR with incomplete platelet recovery. ORR was
      93% in diploid patients and 100% in FLT-3 ITD patients. Levels of NRF2 and CYBB
      were associated with longer survival. CONCLUSION: The combination of vorinostat
      with idarubicin and cytarabine is safe and active in AML.

PMID- 22585697
TI  - Clofarabine plus cytarabine compared with cytarabine alone in older patients with
      relapsed or refractory acute myelogenous leukemia: results from the CLASSIC I
      Trial.
AB  - PURPOSE: To compare the receipt of clofarabine plus cytarabine (Clo+Ara-C arm)
      with cytarabine (Ara-C arm) in patients >= 55 years old with refractory or
      relapsed acute myelogenous leukemia (AML). PATIENTS AND METHODS: Patients were
      randomly assigned to receive either clofarabine (Clo) 40 mg/m(2) or a placebo
      followed by Ara-C 1 g/m(2) for five consecutive days. The primary end point was
      overall survival (OS). Secondary end points included event-free survival (EFS), 4
      month EFS, overall remission rate (ORR; complete remission [CR] plus CR with
      incomplete peripheral blood count recovery), disease-free survival (DFS),
      duration of remission (DOR), and safety. RESULTS: Among 320 patients with
      confirmed AML (median age, 67 years), the median OS was 6.6 months in the Clo+Ara
      C arm and 6.3 months in the Ara-C arm (hazard ratio [HR], 1.00; 95% CI, 0.78 to
      1.28; P = 1.00). The ORR was 46.9% in the Clo+Ara-C arm (35.2% CR) versus 22.9%
      in the Ara-C arm (17.8% CR; P < .01). EFS (HR: 0.63; 95% CI, 0.49 to 0.80; P <
      .01) and 4-month EFS (37.7% v 16.6%; P < .01) favored the Clo+Ara-C arm compared
      with Ara-C arm, respectively. DFS and DOR were similar in both arms. Overall 30
      day mortality was 16% and 5% for CLO+Ara-C and Ara-C arms, respectively. In the
      Clo+Ara-C and Ara-C arms, the most common grade 3 to 4 toxicities were febrile
      neutropenia (47% v 35%, respectively), hypokalemia (18% v 11%, respectively),
      thrombocytopenia (16% v 17%, respectively), pneumonia (14% v 10%, respectively),
      anemia (13% v 0%, respectively), neutropenia (11% v 9%, respectively), increased
      AST (11% v 2%, respectively), and increased ALT (10% v 3%, respectively).
      CONCLUSION: Although the primary end point of OS did not differ between arms,
      Clo+Ara-C significantly improved response rates and EFS. Study follow-up
      continues, and the role of clofarabine in the treatment of adult patients with
      AML continues to be investigated.

PMID- 22585698
TI  - Human epidermal growth factor receptor 2 status and interval breast cancer in a
      population-based cancer registry study.
AB  - PURPOSE: To determine whether human epidermal growth factor receptor 2 (HER2) 
      positive status is associated with risk of breast cancer diagnosis in the
      interval between mammographic screening, we estimated the distribution of
      features of aggressive tumor behavior in a general population with newly
      diagnosed breast cancer and known screening status. PATIENTS AND METHODS: We
      evaluated all invasive breast cancers (N = 641) that were systematically
      collected by the Parma Province Cancer Registry and diagnosed in women age 50 to
      69 years from 2004 to 2007. From this population, 292 screen-detected cancers and
      48 interval cases with negative screening mammograms on expert rereading (true
      interval cancers) were selected for study purposes. Unconditional logistic
      regression adjusted for age and tumor size was used to determine whether interval
      cancers were associated with selected clinicobiologic characteristics. RESULTS:
      Tumors with a high histologic grade (odds ratio [OR], 1.8; 95% CI, 1.2 to 3.8),
      high proliferative rate (OR, 2.4; 95% CI, 1.2 to 4.5), negative estrogen receptor
      status (OR, 1.6; 95% CI, 1.1 to 3.1), or HER2-positive status (OR, 3.4; 95% CI,
      1.7 to 7.1) were more likely to be diagnosed in the interval between screening.
      Women age less than 60 years with HER2-positive breast cancer were four times
      more likely to be diagnosed in the interval between screening compared with only
      a two-fold increased risk for older women. CONCLUSION: This population-based
      cancer registry study demonstrated that HER2-positive tumors account for a
      substantial proportion of mammographic screening failure. The distribution of
      biologic characteristics in screen-detected cancers differs from that observed in
      interval cancers and may account in part for the more aggressive behavior of
      interval-detected cases.

PMID- 22585700
TI  - Personalized medicine: what exactly is it and can we truly measure it?

PMID- 22585699
TI  - Adoption of gene expression profile testing and association with use of
      chemotherapy among women with breast cancer.
AB  - PURPOSE: Gene expression profile (GEP) testing is a relatively new technology
      that offers the potential of personalized medicine to patients, yet little is
      known about its adoption into routine practice. One of the first commercially
      available GEP tests, a 21-gene profile, was developed to estimate the benefit of
      adjuvant chemotherapy for hormone receptor-positive breast cancer (HR-positive
      BC). PATIENTS AND METHODS: By using a prospective registry data set outlining the
      routine care provided to women diagnosed from 2006 to 2008 with HR-positive BC at
      17 comprehensive and community-based cancer centers, we assessed GEP test
      adoption and the association between testing and chemotherapy use. RESULTS: Of
      7,375 women, 20.4% had GEP testing and 50.2% received chemotherapy. Over time,
      testing increased (14.7% in 2006 to 27.5% in 2008; P < .01) and use of
      chemotherapy decreased (53.9% in 2006 to 47.0% in 2008; P < .01). Characteristics
      independently associated with lower odds of testing included African American
      versus white race (odds ratio [OR], 0.70; 95% CI, 0.54 to 0.92) and high school
      or less versus more than high school education (OR, 0.63; 95% CI, 0.52 to 0.76).
      Overall, testing was associated with lower odds of chemotherapy use (OR, 0.70;
      95% CI, 0.62 to 0.80). Stratified analyses demonstrated that for small, node
      negative cancers, testing was associated with higher odds of chemotherapy use
      (OR, 11.13; 95% CI, 5.39 to 22.99), whereas for node-positive and large node
      negative cancers, testing was associated with lower odds of chemotherapy use (OR,
      0.11; 95% CI, 0.07 to 0.17). CONCLUSION: There has been a progressive increase in
      use of this GEP test and an associated shift in the characteristics of and
      overall reduction in the proportion of women with HR-positive BC receiving
      adjuvant chemotherapy.

PMID- 22585701
TI  - My first patient.

PMID- 22585702
TI  - Potential usefulness of single nucleotide polymorphisms to identify persons at
      high cancer risk: an evaluation of seven common cancers.
AB  - PURPOSE: To estimate the likely number and predictive strength of cancer
      associated single nucleotide polymorphisms (SNPs) that are yet to be discovered
      for seven common cancers. METHODS: From the statistical power of published genome
      wide association studies, we estimated the number of undetected susceptibility
      loci and the distribution of effect sizes for all cancers. Assuming a log-normal
      model for risks and multiplicative relative risks for SNPs, family history (FH),
      and known risk factors, we estimated the area under the receiver operating
      characteristic curve (AUC) and the proportion of patients with risks above risk
      thresholds for screening. From additional prevalence data, we estimated the
      positive predictive value and the ratio of non-patient cases to patient cases
      (false-positive ratio) for various risk thresholds. RESULTS: Age-specific
      discriminatory accuracy (AUC) for models including FH and foreseeable SNPs ranged
      from 0.575 for ovarian cancer to 0.694 for prostate cancer. The proportions of
      patients in the highest decile of population risk ranged from 16.2% for ovarian
      cancer to 29.4% for prostate cancer. The corresponding false-positive ratios were
      241 for colorectal cancer, 610 for ovarian cancer, and 138 or 280 for breast
      cancer in women age 50 to 54 or 40 to 44 years, respectively. CONCLUSION:
      Foreseeable common SNP discoveries may not permit identification of small subsets
      of patients that contain most cancers. Usefulness of screening could be
      diminished by many false positives. Additional strong risk factors are needed to
      improve risk discrimination.

PMID- 22585704
TI  - Targeting the Notch pathway: twists and turns on the road to rational
      therapeutics.

PMID- 22585703
TI  - Acute myeloid leukemia and myelodysplastic syndromes after radiation therapy are
      similar to de novo disease and differ from other therapy-related myeloid
      neoplasms.
AB  - PURPOSE: Therapy-related myeloid neoplasms (t-MN) represent a unique clinical
      syndrome occurring in patients treated with chemotherapy and/or external-beam
      radiation (XRT) and are characterized by poorer prognosis compared with de novo
      disease. XRT techniques have evolved in recent years and are associated with
      significantly reduced bone marrow exposure. The characteristics of post-XRT t-MN
      in the current era have not been studied. PATIENTS AND METHODS: We analyzed
      patients who developed acute myeloid leukemia (AML) or myelodysplastic syndromes
      (MDS) after XRT alone (47 patients) or cytotoxic chemotherapy/combined-modality
      therapy (C/CMT, 181 patients) and compared them with patients with de novo MDS or
      AML (222 patients). We estimated bone marrow exposure to radiation and compared
      the clinical, pathologic, and cytogenetic features and outcome of the XRT
      patients with the C/CMT patients and with patients with de novo MDS and AML.
      RESULTS: Patients with t-MN after XRT alone had superior overall survival (P =
      .006) and lower incidence of high-risk karyotypes (P = .01 for AML and < .001 for
      MDS) compared with patients in the C/CMT group. In contrast, there were no
      significant differences in survival or frequency of high-risk karyotypes between
      the XRT and de novo groups. CONCLUSION: AML and MDS diagnosed in the past decade
      in patients after receiving XRT alone differ from t-MN occurring after C/CMT and
      share genetic features and clinical behavior with de novo AML/MDS. Our results
      suggest that post-XRT MDS/AML may not represent a direct consequence of radiation
      toxicity and warrant a therapeutic approach similar to de novo disease.

PMID- 22585705
TI  - Unstable angina associated with cisplatin and carboplatin in a patient with
      advanced melanoma.

PMID- 22585706
TI  - Plasma-derived MHC class II+ exosomes from tumor-bearing mice suppress tumor
      antigen-specific immune responses.
AB  - Tumor-specific immunosuppression is frequently observed in tumor-bearing hosts.
      Exosomes are nano-sized, endosomal-derived membrane vesicles secreted by most
      tumor and hematopoietic cells and have been shown to actively participate in
      immune regulation. We previously demonstrated that antigen-specific
      immunosuppressive exosomes could be isolated from the blood plasma of antigen
      immunized mice. Here, we demonstrate that plasma-derived exosomes isolated from
      mice bearing OVA-expressing tumors were able to suppress OVA-specific immune
      responses in a mouse delayed-type hypersensitivity model. Enrichment of tumor
      derived exosomes in the plasma of mice bearing subcutaneous melanoma was not
      detected using an exosome-tagging approach. Instead, depletion of MHC class II(+)
      vesicles from plasma-derived exosomes or using plasma-derived exosomes isolated
      from MHC class II-deficient mice resulted in significant abrogation of the
      suppressive effect. These results demonstrate that circulating host-derived, MHC
      class II(+)  exosomes in tumor-bearing hosts are able to suppress the immune
      response specific to tumor antigens.

PMID- 22585707
TI  - Improved multiplex ligation-dependent probe amplification analysis identifies a
      deleterious PMS2 allele generated by recombination with crossover between PMS2
      and PMS2CL.
AB  - Heterozygous PMS2 germline mutations are associated with Lynch syndrome. Up to
      one third of these mutations are genomic deletions. Their detection is
      complicated by a pseudogene (PMS2CL), which--owing to extensive interparalog
      sequence exchange--closely resembles PMS2 downstream of exon 12. A recently
      redesigned multiplex ligation-dependent probe amplification (MLPA) assay
      identifies PMS2 copy number alterations with improved reliability when used with
      reference DNAs containing equal numbers of PMS2- and PMS2CL-specific sequences.
      We selected eight such reference samples--all publicly available--and used them
      with this assay to study 13 patients with PMS2-defective colorectal tumors. Three
      presented deleterious alterations: an Alu-mediated exon deletion; a 125-kb
      deletion encompassing PMS2 and four additional genes (two with tumor-suppressing
      functions); and a novel deleterious hybrid PMS2 allele produced by recombination
      with crossover between PMS2 and PMS2CL, with the breakpoint in intron 10 (the
      most 5' breakpoint of its kind reported thus far). We discuss mechanisms that
      might generate this allele in different chromosomal configurations (and their
      diagnostic implications) and describe an allele-specific PCR assay that
      facilitates its detection. Our data indicate that the redesigned PMS2 MLPA assay
      is a valid first-line option. In our series, it identified roughly a quarter of
      all PMS2 mutations.

PMID- 22585708
TI  - Impact of esophageal invasion on clinicopathological characteristics and long
      term outcome of adenocarcinoma of the subcardia.
AB  - BACKGROUNDS AND OBJECTIVES: A different classification system was used in the 7th
      edition of the TNM classification for adenocarcinoma of the subcardia either with
      or without esophageal invasion. The aim of this study was to clarify the
      clinicopathological and survival impact of esophageal invasion. METHODS: The
      present study included 351 patients who underwent gastrectomy for adenocarcinoma
      located within 5 cm of the esophagogastric junction. The clinicopathological
      characteristics and survival curves were compared between patients with
      esophageal invasion [E (+) group, n = 125] and without esophageal invasion [E (-)
      group, n = 226]. RESULTS: Patients in the E (+) group had more advanced disease.
      The 5-year survival rate following macroscopic curative resection was
      significantly better in the E (-) group (80.8%) than in the E (+) (48.7%, P <
      0.001), even after stratification by the pathological stage and nodal status.
      Multivariate analysis identified esophageal invasion (hazard ratio; 3.323, 95%
      confidential interval; 1.815-6.082) as one of the independent prognostic factors.
      CONCLUSIONS: Esophageal invasion affected the clinicopathological characteristics
      and long-term outcome of patients. Further study is necessary to clarify whether
      patients with esophageal invasion should be classified using the system for
      esophageal cancer or by another method.

PMID- 22585709
TI  - Amplification and overexpression of the ABCC3 (MRP3) gene in primary breast
      cancer.
AB  - The ATP-binding cassette (ABC) of active transporters comprises a group of
      proteins that which facilitate efflux of anticancer drugs from cancer cells. We
      focused on the gene amplification and protein expression of ABCC3 (also known as
      MRP3) in breast cancer cell lines and clinical tumor samples. Fluorescence and
      chromogenic in situ hybridization, using an ABCC3-specific probe, was used to
      analyze 11 breast cancer cell lines and 112 clinical tumor samples. The results
      of ABCC3 were correlated with the amplification status of HER2 and topoisomerase
      II alpha (TOP2A), which are located close to ABCC3 at 17q12-q21.
      Immunohistochemistry was used to assess ABCC3 protein overexpression. Of the cell
      lines studied 6 HER2-positive lines and 1 HER2-negative line exhibited
      amplification of ABCC3. In the HER-2-negative clinical tumor samples, only 4/55
      (7.3%) exhibited ABCC3 amplification. In the HER2-positive tumors, ABCC3 was
      amplified in 16/57 tumors (28.1%, P=0.0059). TOP2A did not exhibit any consistent
      coamplification pattern. ABCC3 (MRP3) protein overexpression was more common in
      tumors with gene amplification (P=0.069). In silico analysis of 804 breast
      cancers with matched gene expression and copy number microarray data revealed
      significant differences ABCC3 across the molecular subtypes. Specifically,
      increased ABCC3 mRNA and gene copy numbers were most prominent in HER2 amplified
      and/or HER2-enriched classified tumors. Moreover, differential ABCC3 mRNA levels
      were found within the HER-2 amplified subset when stratified by the estrogen
      receptor status. We conclude that ABCC3 is frequently amplified and overexpressed
      in HER2-positive breast cancer, and something that warrants further studies
      correlating the results with therapeutic outcome.

PMID- 22585711
TI  - The correlations between the expression of FGFR4 protein and clinicopathological
      parameters as well as prognosis of gastric cancer patients.
AB  - BACKGROUND: Fibroblast growth factor receptor 4 (FGFR4) was seldom investigated
      in gastric cancer (GC). The purpose of the study was to elucidate the expression
      of FGFR4 protein in GC and related clinical significance. METHODS: Ninety-four
      paraffin-embedded tumor specimens were obtained from Cancer Hospital, Fudan
      University. The expression of FGFR4 as well as p53, p21, EGFR, neu, c-myc, and
      PCNA were detected by immunohistochemical method. Then, correlation analysis and
      survival analysis were performed. RESULTS: The expression rate of FGFR4 protein
      in GC tissues and normal stomach tissues was 93.6% and 30.8%, respectively (P =
      0.000). The expression of FGFR4 was positively correlated with the expression of
      p21, neu and PCNA (P-value was 0.009, 0.012, and 0.018, respectively). Subgroup
      analysis showed that compared to low expression group, the prognosis of patients
      with III/IV stage and negative expression of p21 in high expression group of
      FGFR4 were worse (P = 0.048, 0.041, respectively). Multivariate analysis showed
      that TNM stage was the independent prognostic factor in high expression group
      (HR, 11.593; 95% CI, 3.532-18.058; P = 0.000). CONCLUSIONS: High expression of
      FGFR4 protein, accelerating the progression of advanced GC, might be associated
      with a poor prognosis in patients with advanced FC.

PMID- 22585710
TI  - Lack of T cells in Act1-deficient mice results in elevated IgM-specific
      autoantibodies but reduced lupus-like disease.
AB  - Act1 is a negative regulator of B-cell activation factor of the TNF family (BAFF)
      and CD40L-induced signaling. BALB/C mice lacking Act1 develop systemic
      autoimmunity resembling systemic lupus erythematosus (SLE) and Sjogren's syndrome
      (SjS). SLE and SjS are characterized by anti-nuclear IgG autoantibody (ANA-IgG)
      production and inflammation of peripheral tissues. As autoantibody production can
      occur in a T-cell dependent or T-cell independent manner, we investigated the
      role of T-cell help during Act1-mediated autoimmunity. Act1-deficiency was bred
      onto C57Bl/6 (B6.Act1(-/-) ) mice and B6.TCRbeta(-/-) TCRdelta(-/-) Act1(-/-) 
      (TKO) mice were generated. While TCRbeta/delta-sufficient B6.Act1(-/-)  mice
      developed splenomegaly and lymphadenopathy, hypergammaglobulinemia, elevated
      levels of ANA-IgG, and kidney pathology, TKO mice failed to develop any such
      signs of disease. Neither B6.Act1(-/-)  nor TKO mice developed SjS-like disease,
      suggesting that epigenetic interactions on the BALB/C background are responsible
      for this phenotype in BALB/C.Act1(-/-)  mice. Interestingly, BAFF-driven
      transitional B-cell abnormalities, previously reported in BALB/C.Act1(-/-)  mice,
      were intact in B6.Act1(-/-)  mice and largely independent of T cells. In
      conclusion, T cells are necessary for the development of SLE-like disease in
      B6.Act1(-/-)  mice, but not BAFF-driven transitional B-cell differentiation.

PMID- 22585712
TI  - Differential expression of RON in small and non-small cell lung cancers.
AB  - RON is a MET related receptor tyrosine kinase (RTK) and its natural ligand is
      macrophage stimulating protein (MSP). RON plays a very important role in the
      regulation of inflammation. Several studies have previously reported
      overexpression of RON in a variety of cancers including lung and identified
      numerous RON alternate splice forms that very likely contribute to tumor growth
      and metastasis. Here, we have analyzed the expression of total RON protein as
      well as its kinase-active form (phospho-RON) in 175 archival lung tumor FFPE
      (formalin fixed paraffin embedded) samples that included non-small-cell lung
      cancer (NSCLC) and small cell lung cancer (SCLC), and their metastatic forms. The
      frequency and intensity of RON protein expression was much higher in lung tumors
      of neuroendocrine origin such as SCLC and in secondary tumors that metastasized
      to brain. In addition, the majority of the expressed RON protein was phospho-RON.
      We also identified 62, and 30 kDa isoforms of RON (GenBank accession numbers are
      JN689381 and JN689382) using RNA isolated from pooled lung cancer cell lines and
      RT-PCR. A majority of the NSCLC cell lines expressed a 150 kDa band that
      corresponded to the RON beta chain and 120 kDa band in the panel of SCLC cell
      lines tested. RON was expressed on the cell surface in NSCLC cell lines. Finally,
      knock down of RON expression resulted in a significant loss in viability as well
      as motility in lung cancer cells suggesting that RON is a potential therapeutic
      target.

PMID- 22585713
TI  - RNAi screen for kinases and phosphatases that play a role in antigen presentation
      by dendritic cells.
AB  - Effective CD8(+)  T-cell responses against tumor or microbial antigens that are
      not directly expressed in antigen-presenting cells (APCs) depend on the cross
      presentation of these antigens on MHC class I in APCs. To identify signaling
      molecules that regulate cross-presentation, we used lentiviral-based RNA
      interference to test the roles of hundreds of kinases and phosphatases in this
      process. Our study uncovered eight previously unknown genes, consisting of one
      positive and seven negative regulators of antigen cross-presentation. Depletion
      of Acvr1c, a type I receptor for TGF-beta family of signaling molecules, led to
      an increase in CD80 and CD86 co-stimulator surface expression and secreted IL-12
      in mouse bone marrow-derived DCs, as well as antigen-specific T-cell
      proliferation.

PMID- 22585714
TI  - HIV replication is associated with increased severity of liver biopsy changes in
      HIV-HBV and HIV-HCV co-infection.
AB  - Histological parameters were assessed in liver biopsies (n = 48) performed in
      patients co-infected with human immunodeficiency virus (HIV) and hepatitis B
      virus (HBV) and/or hepatitis C virus (HCV) in order to evaluate factors which
      were associated with significant liver disease. Necroinflammation and fibrosis
      was scored by the Ishak classification system, and binary logistic regression
      analysis was used to assess HIV and antiretroviral-related determinants of
      necroinflammation and fibrosis. A total of 46 biopsies were included; 33 were
      from HIV-positive patients co-infected with HCV and 15 biopsies were from HIV
      positive patients co-infected with HBV. One HIV-positive patient was co-infected
      with HBV and HCV. Median biopsy inflammatory grade for the cohort was 8.5 (IQR 6
      10), the median fibrosis Stage 2 (IQR 1.8-4), and the median steatosis score was
      1 (IQR 0-2). At the univariate level, HIV-related variables that were
      significantly associated with more severe biopsy changes were higher HIV RNA at
      the time of biopsy (associated with inflammatory Grade 10+; P = 0.018) and any
      exposure to didanasine (ddI) or stavudine (D4T; associated with fibrosis Stage
      3+; P = 0.022). HIV RNA at the time of biopsy remained significant at the
      multivariate level. Patients with HIV hepatitis co-infection in this cohort had
      surprisingly mild changes in liver histology, and there were no statistically
      significant differences between biopsy results in HBV compared to HCV co
      infection. The association between HIV RNA and necroinflammation supports current
      recommendations for earlier initiation of HAART in patients with HIV-hepatitis co
      infection.

PMID- 22585715
TI  - Characterization of HIV-1 subtypes and drug resistance mutations among
      individuals infected with HIV in Georgia.
AB  - In order to describe HIV-1 subtypes and drug resistance mutations in Georgia,
      blood samples from 153 patients infected with HIV-1 collected from 2006 to 2008
      were genotyped. Of these, 126 samples were from newly diagnosed, antiretroviral
      (ARV)-naive patients and 27 from ARV-treated patients. Partial pol region
      sequences were used to identify drug resistance mutations and to conduct
      phylogenetic analysis for subtype determination. The results indicated that 138
      (90.2%) patients harbored subtype A viruses, 11 (7.2%) carried subtype B virus,
      two subtype G (1.3%), one (0.6%) subtype F and one (0.6%) 03_AB recombinant. All
      subtype A strains clustered with the Former Soviet Union A (A FSU) subtype. Among
      patients with no prior exposure to ARVs, mutations associated with resistance
      were detected in five patients: three (2.4%) patients had reverse transcriptase
      (RT) inhibitor mutations and two other patients had the protease (PI) inhibitor
      associated mutation M46I. PI mutation V77I was found in 42 of subtype A isolates.
      Of 27 ARV-treated patients, 22 (81.5%) harbored at least one nucleoside reverse
      transcriptase inhibitors (NRTI), a non-NRTI (NNRTI) and/or a PI mutation. The
      most common NRTI resistance mutation was M184V/I (74.1%). Frequency of thymidine
      analog mutations was relatively low (25.9%). With regard to NNRTI mutations,
      G190S/A was the most frequent mutation, which might be a preferred mutations for
      subtype A. Georgia's HIV epidemic continues to be dominated by Subtype A FSU. The
      prevalence of transmitted drug resistance is low, but has the potential to
      increase with increasing use of ARVs.

PMID- 22585716
TI  - Hepatitis C virus related hepatocellular carcinoma: a case control study from
      India.
AB  - Infection with hepatitis C virus (HCV) is a major risk factor for hepatocellular
      carcinoma (HCC) in India. The study was designed to investigate the clinical and
      molecular profiles of HCV related HCC cases in Indian patients. In a prospective
      study, 68 HCV related HCC, 55 HCV related chronic hepatitis, and 68 HCV related
      patients with cirrhosis were included. Glutathione S-transferase gene
      polymorphism was analyzed in all the cases. The sex ratios were 5.18:1, 1.39:1,
      and 0.83:1 with mean age of 50.57 +/- 12.47, 39.41 +/- 13.34, and 46.08 +/- 15.06
      years, respectively, in three groups. Amongst the HCV related HCC cases seen in
      India, 49.2% (30 out of 68) were with Okuda stage I while 34.4% (21 out of 68)
      cases were classified as stage II. Older age, poor standards of living, HCV
      genotype 4, smoking, and null genotypes of GST were the risk factors associated
      significantly with the development of HCC. In 55.9% cases (38 out of 68) the size
      of the tumor was >=5 cm while in 38.2% cases (26 out of 68) the size was between
      2 and 5 cm, indicating an advanced stage of the disease at presentation.

PMID- 22585717
TI  - Inter-genotypic recombinant hepatitis C virus strains in Japan noted by
      discrepancies between immunoassay and sequencing.
AB  - Genetic recombination plays a significant role in the survival and evolution of
      hepatitis C virus (HCV), but methodological limitations have hindered the
      exploration of genetic recombination. HCV serotypes were evaluated in 104
      patients with chronic hepatitis C when they initially presented in hospitals.
      Subsequently, HCV genotypes were analyzed using primers for core gene and NS5B
      gene. Near-complete nucleotide sequences of eight HCV isolates from two suspected
      patients with 2b/1b recombinant HCV were analyzed by amplification of nine
      overlapping regions of HCV-specific oligonucleotide primers at different time
      points: (i) at the first admission; (ii) before and (iii) after interferon
      therapy; and (iv) after development of hepatocellular carcinoma. The nucleotide
      sequence of eight HCV isolates obtained was 9,321-9,471 nucleotides in length,
      comprising a single ORF (polyprotein of 3,014 amino acids.) and segregated into
      discordant genotypes of 2b and 1b HCV with a recombination junction in NS2. This
      study highlights the need for more precise characterization of HCV in clinical
      samples where there is a discrepancy between immunoassays and sequencing. It also
      demonstrates the circulation of novel inter-genotypic recombinant HCV in Japan,
      because the cross over point of 2b/1b recombinant HCV in eight clinical isolates
      of these two patients differed from previously reported HCV recombinant from the
      Philippines and Japan.

PMID- 22585718
TI  - Molecular characterization of hepatitis E virus in patients with acute hepatitis
      in Venezuela.
AB  - Hepatitis E virus (HEV) causes a common infection in developing countries. HEV
      infection occurs as outbreaks, as sporadic clinical cases and as large epidemics
      in endemic areas. The objective of this study was to determine the presence of
      HEV infection in patients with clinical suspicion of hepatitis A virus (HAV)
      infection, referred to the Instituto Nacional de Higiene "Rafael Rangel" in
      Venezuela. Seventy-four sera were tested for anti-HAV and anti-HEV IgM
      antibodies. HEV-RNA was amplified from anti-HEV IgM positive sera using nested
      reverse transcription polymerase chain reaction for ORF1 (RNA dependent RNA
      polymerase region) and the amplicons sequenced for phylogenetic analysis. The
      frequency of anti-HEV IgM was 22/74 (30%) in the samples tested. Dual infection
      with HAV and HEV was found in 31% (12/39) of anti-HAV IgM positive patients.
      Viremia was detected in 3/22 (14%) of sera positive for anti-HEV IgM. Two HEV
      strains were classified as genotype 1 and one as genotype 3, which were closely
      related to Yam 67 (north of India) and US1 isolates from the USA, respectively.
      These findings suggest that HEV is an important cause of acute viral hepatitis in
      Venezuela as a single infection or co-infection with HAV, with high morbidity in
      children and young adults suggesting that this infection is endemic in Venezuela.

PMID- 22585719
TI  - Factors influencing inadequate or suboptimal response to adefovir with or without
      genotypic resistance.
AB  - The aim of the study was to explore the factors in inadequate-responders to
      treatment with adefovir (ADV) with or without genotypic resistance. The reverse
      transcriptase (RT) gene of hepatitis B virus (HBV) was sequenced in 161 patients
      with inadequate-response to ADV and analyzed for HBV genotypes using a
      phylogenetic approach. Seventy-six patients (47.2%) were found to carry the
      rtA181V/T/S or rtN236T residue substitution, and most of them had viral rebound.
      In the patients with viral rebound and ADV genotypic resistance, 19 (25.7%)
      showed rtA181V/T/S + rtN236T substitutions. In the other patients, it was found
      that HBV genotypes and cirrhosis influenced the selection of ADV-resistant
      positions by univariate analysis and multiple logistic regression analysis. The
      rtN236T was more frequent in patients with genotype B, and the rtA181V/T/S was
      more common in patients with genotype C (chi(2)  = 11.543, P = 0.001). Multiple
      logistic regression analysis showed that the rtN236T and time resistant strains
      occurred during ADV-treatment were statistically significant for influencing
      rtA181 variation types (P = 0.007 and P = 0.024, respectively), and the
      occurrence of rtA181T was found to be significantly earlier than rtA181V. In
      conclusion, genotypic resistance was not detected in the majority of primary
      nonresponders to ADV when compared to the patients with viral rebound. The
      different HBV genotypes influence the selection of ADV-resistant mutation
      positions. The rtA181T occurs more frequently in patients with the rtN236T and it
      occurs earlier when compared to the rtA181V. These findings suggest that early
      judgment of adequate response and making a decision for interference in patients
      treated with ADV are of importance in clinical practice.

PMID- 22585720
TI  - Phylogenetic analysis of the complete genome of 11 BKV isolates obtained from
      allogenic stem cell transplant recipients in Ireland.
AB  - BK polyomavirus (family Polyomaviridae) may cause hemorrhagic cystitis (BKV-HC)
      in hematopoietic stem cell transplant recipients. Eleven complete BKV genomes
      (GenBank accession numbers: JN192431-JN192441) were sequenced from urine samples
      of allogenic hematopoietic stem cell transplant recipients and compared to
      complete BKV genomes in the published literature. Of the 11 isolates, seven (64%)
      were subgroup Ib-1, three (27%) isolates belonged to subgroup Ib-2 and a single
      isolate belonged to subtype III. The analysis of single-nucleotide polymorphisms
      in this study showed that isolates could be subclassified into subtypes I-IV and
      subgroups Ib-1 and Ib-2 on the basis of VP1 of the first part of the Large T
      antigen (LTag). The non-coding control region (NCCR) of the 11 isolates was also
      sequenced. These sequences showed that there was consistent sequence homology
      within subgroups Ib-1 and Ib-2. Two new mutations were described in the isolates,
      G->C at O(84) in isolate SJH-LG-310, and a deletion at R(2-7) in isolate SJH-LG
      309. No known transcription factor is thought to be present at the site of either
      of these mutations. There were no rearrangements seen in isolates and this may be
      because the patients were not followed up over time. There were five nucleotide
      positions at which subgroup Ib-1 isolated differed from subgroup Ib-2 isolates in
      the NCCR sequence, O(41) , P(18) , P(31) , R(4) , and S(18) . The mutation O(41)
      is present in the promoter granulocyte/macrophage stimulating factor) gene and
      the P(31) mutation is present in the NF-1 gene.

PMID- 22585721
TI  - Type 1 diabetes associated and tissue transglutaminase autoantibodies in patients
      without type 1 diabetes and coeliac disease with confirmed viral infections.
AB  - Coeliac disease and type 1 diabetes are autoimmune diseases that may share the
      same initiating environmental factors. In this study, the occurrence of type 1
      diabetes associated autoantibodies (GADA and IA-2A) and tissue transglutaminase
      autoantibodies (TGA) was determined in patients with confirmed viral infections
      and no signs of type 1 diabetes or coeliac disease. Serum samples from 82 Cuban
      patients tested positive for PCR and IgG specific to enterovirus (HEV, serotype
      echovirus 16, 20 samples), Epstein-Barr virus (EBV, 20 samples), cytomegalovirus
      (CMV, 21 samples), and hepatitis C virus (HCV, 21 samples); and sera from 164
      controls negative serologically to EBV, CMV, HCV, and echovirus 16 were enrolled
      in the study. All subjects were screened for GADA, IA-2A, and TGA. The prevalence
      of TGA in patients infected with HEV, EBV, CMV, or HCV was 55% (11/20), 25%
      (5/20), 9.5% (2/21), and 9.5% (2/21), respectively. GADA and IA-2A were found in
      15% (3/20) and 25% (5/20) of patients infected with HEV. None of the patients
      infected by EBV, CMV, and HCV had GADA or IA-2A. All children infected with HEV
      who were positive for type 1 diabetes-associated autoantibodies were also TGA
      positive. None of the sera from uninfected subjects were positive for GADA, IA-2A
      or TGA. In conclusion, TGA can develop during infection with HEV, EBV, CMV, or
      HCV, while the emergence of islet cell related autoantibodies is restricted to
      HEV infections. The findings suggest that HEV may be a shared environmental
      factor for the development of islet and gut-related autoimmunity.

PMID- 22585722
TI  - Prevalence of human papillomavirus types in cervical lesions from women in rural
      Western India.
AB  - Cervical cancer is the most common cancer among women in many areas of India
      which contributes for a fifth of the global burden of disease. Persistent
      infection with one of the high-risk human papillomaviruses (HPV) has been
      established as the cause for cervical cancer and the documentation of the
      prevalence of HPV types in cervical cancer in different regions of India is
      useful for a prevention program combining both screening and vaccination. In this
      study, the HPV type distribution and the frequency of p16(INK4a) immunoexpression
      have been determined in 125 cases of inflammatory lesions or grade 1 cervical
      intraepithelial neoplasia, 74 cases of grade 2, 72 cases of grade 3, and 113
      cervical cancer cases diagnosed among women from rural Solapur and Osmanabad
      districts, Maharashtra. The overall prevalence of high-risk HPV was 37.6% in
      inflammatory lesions or grade 1 cervical intraepithelial neoplasia, 63.5% in
      grade 2, 97.2% in grade 3 and 92% in cervical cancer cases. HPV 16 and HPV 18
      were detected in 80.6% of grade 3 cervical intraepithelial neoplasia and 86.5% of
      cervical cancer cases. 94.7% of the cervical cancer and 84.4% of the high grade
      lesions with a strong and full thickness staining for p16(INK4a) were positive
      for HPV infection; p16(INK4a) immunoexpression increased with worsening grade of
      cervical intraepithelial neoplasia. The HPV genotyping data showing a high HPV 16
      and 18 prevalence in cancer specimens indicate that prophylactic HPV 16/18
      vaccination would have a significant impact on the prevention of cervical cancer
      in India.

PMID- 22585723
TI  - The characterization of monoclonal antibodies to human metapneumovirus and the
      detection of multiple forms of the virus nucleoprotein and phosphoprotein.
AB  - Little is known of the proteome of human metapneumovirus (HMPV). In this study a
      panel of monoclonal antibodies to the virus have been characterized and used to
      identify viral proteins present in infected cell lysates. Of thirteen anti-HMPV
      monoclonal antibodies four reacted with recombinant fusion glycoprotein and one
      with recombinant G glycoprotein by immunofuorescence but not in western blots
      suggesting that they recognize conformation dependent epitopes. The specificity
      of the remaining antibodies were determined by MALDI/TOF analysis of the proteins
      they immunoprecipitated from HMPV infected cell lysates and by western blotting.
      Five MAbs bound to the nucleoprotein and three to the phosphoprotein. In western
      blots of lysates of cells infected with low passage HMPV, the anti-nucleoprotein
      MAbs stained a single polypeptide corresponding in size to the full length
      nucleocapsid protein. On repeated passage of the virus in cell culture, however,
      a second, smaller band appeared which may result from internal initiation of
      translation within the nucleocapsid gene as described for avian metapneumovirus.
      Antibodies to the phosphoprotein, besides the full length form, also recognized
      multiple polypeptides in infected cell lysates, with patterns differing for the
      two subtypes A and B. The possibility that these too may derive by internal
      initiation of translation is discussed.

PMID- 22585724
TI  - The viral etiology of an influenza-like illness during the 2009 pandemic.
AB  - Many viruses are known to cause influenza-like illness (ILI); however, in nearly
      50% of patients, the etiologic agent remains unknown. The distribution of viruses
      in patients with ILI was investigated during the 2009 A/H1N1 influenza pandemic
      (A/H1N1p). From June 2009 to January 2010, 660 patients with suspected influenza
      were questioned and examined, and nasal swabs were collected. All patient samples
      were tested for influenza virus, and 286 negative nasal swabs were tested further
      for 18 other respiratory viruses using real-time RT-PCR. Two waves of ILI were
      observed in the epidemic curve (weeks 35-42 and 42-49). At least eight viruses co
      circulated during this period: human rhinovirus (HRV) (58), parainfluenza 1-4
      viruses (PIV) (9), human Coronavirus (hCoV) OC43 (9), enterovirus (5), adenovirus
      (AdV) (4), and human metapneumovirus (hMPV) (2); however, 204 samples remained
      negative for all viruses tested. ILI symptoms, according to the Centers for
      Disease Control and Prevention criteria for ILI definition, were reported in 75%
      of cases. These patients had positive swabs for A/H1N1p, HRV, hCoV-OC43, PIV,
      AdV, and hMPV without significant difference with non-ILI patients. This study
      found that many respiratory viruses circulated during this period and that the
      A/H1N1p did not impact on the kinetics of other respiratory viruses. The
      proportion of non-documented cases remains high. ILI could not distinguish
      A/H1N1p infection from that due to other respiratory viruses. However, in
      multivariate anlaysis, cough, chills, hyperemia, and dyspnea were associated
      significantly with influenza virus versus other respiratory viruses.

PMID- 22585725
TI  - Picornaviruses in cerebrospinal fluid of children with meningitis in Luanda,
      Angola.
AB  - Human enteroviruses are the most common cause of viral meningitis. Viral
      bacterial interaction may affect the clinical course and outcome of bacterial
      meningitis. In Africa, viruses might be responsible for 14-25% of all meningitis
      cases. However, only few studies from Africa have reported detection of viruses
      in the cerebrospinal fluid (CSF) or mixed viral-bacterial infections of the
      central nervous system (CNS). The aim of the present study was to investigate the
      presence of picornaviruses in the CSF of children suffering from meningitis in
      Luanda, Angola. The study included 142 consecutive children enrolled in a
      prospective study of bacterial meningitis in Luanda between 2005 and 2006, from
      whom a CSF sample was available. CSF samples were obtained at hospital admission,
      stored in a deep-freeze, and transported to Finland for testing by real-time PCR
      for picornaviruses. Enteroviruses were detected in 4 (3%) of 142 children with
      presumed bacterial meningitis. A 5-month-old girl with rhinovirus and Haemophilus
      influenzae meningitis recovered uneventfully. An 8-year-old girl with human
      enterovirus and pneumococcal meningitis developed no sequelae. A 2-month-old girl
      with human enterovirus and malaria recovered quickly. A 7-month-old girl with
      human enterovirus was treated for presumed tuberculous meningitis and survived
      with severe sequelae. Mixed infections of the CNS with picornaviruses and
      bacteria are rare. Detection of an enterovirus does not affect the clinical
      picture and outcome of bacterial meningitis.

PMID- 22585726
TI  - Specific increase in local IL-17 production during recovery from primary RSV
      bronchiolitis.
AB  - Although Respiratory syncytial virus (RSV) bronchiolitis is the most important
      cause of hospital admission for infants during the winter season, the
      pathogenesis is largely unknown. Interleukin-17 (IL-17) concentrations were
      studied in nasopharyngeal aspirates from 21 non-ventilated and 17 ventilated
      infants admitted to hospital with RSV bronchiolitis at time of admission and
      discharge from the hospital. On admission, nasopharyngeal concentrations of most
      cytokines and chemokines were lower in non-ventilated infants than in ventilated
      infants, reaching statistical significance for Eotaxin, IL-1alpha, and IL-6.
      During course of disease, nasopharyngeal concentrations of most cytokines and
      chemokines decreased, reaching statistical significance for IL-6 and IP-10.
      However, nasopharyngeal IL-17 concentrations were higher at discharge than at
      admission in children with non-ventilated RSV disease (209-101 pg/ml, P = 0.008),
      a response pattern not observed in ventilated RSV patients nor for other
      cytokines or chemokines. It is speculated that local IL-17 production may be
      involved during convalescence from RSV bronchiolitis in non-ventilated patients
      by facilitating innate and adaptive antiviral immune responses. The role of IL-17
      in the pathogenesis of RSV bronchiolitis is to be explored further.

PMID- 22585727
TI  - Emergence of a new norovirus GII.6 variant in Japan, 2008-2009.
AB  - Norovirus (NoV) is recognized as one of the most common causative agents of
      diarrhea disease in young children. A total of 187 fecal specimens collected from
      non-hospitalized children with acute gastroenteritis in Shizuoka, Japan during
      July 2008 to June 2009 were investigated for the presence of diarrhea viruses by
      a multiplex RT-PCR. Diarrhea viruses were overall detected in 158 of 187 (84.5%).
      Of the viruses detected, NoV was the most prevalent (55.6%). Most of the NoV
      sequences belonged to GII.4 (53.8%). NoV GII.6 emerged as the second most common
      strain (40.4%). The full-length capsid sequences of five representative Shizuoka
      GII.6 strains were compared with all 12 GII.6 strains available in GenBank
      database between 1990 and 2009. At least three distinct GII.6 subclusters (a-c)
      appeared in different parts of the world. Shizuoka GII.6 strains formed their own
      subcluster c, distinct from other complete GII.6 reference sequences. The
      Shizuoka strains had significant amino acid divergence, particularly in the P2
      domain up to 10.9-17.5% and contained eight unique mutations in the P domains,
      compared with subcluster a and b viruses. The homology model showed that the
      eight mutations were predicted to be located at the surface-exposed P1 and P2
      domains. The data suggest the emergence of a new NoV GII.6 variant in Shizuoka,
      with a high level of genetic variation.

PMID- 22585728
TI  - Determinants of response to triple therapy of telaprevir, peginterferon, and
      ribavirin in previous non-responders infected with HCV genotype 1.
AB  - Patients who do not achieve sustained virological response to
      telaprevir/peginterferon (PEG-IFN)/ribavirin need to be identified. Predictive
      factors of virological response to the triple therapy in non-responders to
      previous PEG-IFN/ribavirin therapy are not clear. The aims of this study were to
      determine the predictive factors of virological response to a 24-week regimen of
      triple therapy in 15 non-responders to previous PEG-IFN/ribavirin therapy among
      61 Japanese adults infected with HCV genotype 1. Overall, sustained virological
      response and end-of-treatment response were achieved by 27% and 60%,
      respectively. Telaprevir-resistant variants (by direct sequencing) appeared
      during or after treatment in 82% of patients who did not show sustained
      virological response, but disappeared at the end of study, except for one patient
      with resistant variant at baseline. Substitution at aa 70 (Arg70) and type of
      previous response to PEG-IFN/ribavirin (partial response) were identified as
      significant determinants of sustained virological response. In addition, alpha
      fetoprotein level (<10 ug/L) and type of previous response (partial response)
      were identified as significant determinants of end-of-treatment response.
      Prediction of response to therapy based on the combination of these factors had
      high sensitivity, specificity, positive, and negative predictive values. In
      conclusion, this study identified amino acid substitution of the core region,
      alpha-fetoprotein level, and type of previous response as predictors of
      virological response to telaprevir/PEG-IFN/ribavirin in patients infected with
      HCV genotype 1b who had not responded to previous PEG-IFN/ribavirin therapy.

PMID- 22585729
TI  - ITPA gene polymorphisms significantly affect hemoglobin decline and treatment
      outcomes in patients coinfected with HIV and HCV.
AB  - Published studies have described a strong association with a single-nucleotide
      polymorphism (SNP) in the inosine triphosphate pyrophosphatase (ITPA) gene and
      ribavirin (RBV)-induced hemolytic anemia in HCV-infected patients receiving
      pegylated interferon (pegIFN) and RBV. This study sought to evaluate the effect
      of these polymorphisms on anemia, hemoglobin reduction, HCV kinetics, and
      treatment outcomes. Sixty-three patients coinfected with HIV and HCV and 58
      patients infected with HCV only were treated with pegIFN/RBV were genotyped using
      the ABI TaqMan allelic discrimination kit for the 2 ITPA SNP variants rs1127354
      and rs7270101. A composite variable of ITPA deficiency using both SNPs was
      created as previously reported. Statistical analysis was performed using Mann
      Whitney test or Chi square/Fishers exact test for categorical data and mixed
      model analysis for multiple variables. Thirty-five patients (30%) were predicted
      to have reduced ITPA activity. ITPA deficiency was found to be protective against
      the development of hemoglobin reduction >3 g/dl over the course of treatment. The
      rates of hemoglobin reduction >3 g/dl decreased in correlation with the severity
      of ITPA deficiency. ITPA deficiency was associated with slower hemoglobin decline
      early in treatment (week 4, P = 0.020) and rapid virologic response (RVR) at week
      4 (P = 0.017) in patients coinfected with HIV and HCV. ITPA polymorphisms are
      associated with hemoglobin decline and in patients coinfected with HIV and HCV it
      is also associated with early virologic outcomes. Determination of ITPA
      polymorphisms may allow prediction of RBV-induced anemia and earlier initiation
      of supportive care to ensure optimal therapeutic outcomes.

PMID- 22585730
TI  - Association between human papillomavirus infection and cytological abnormalities
      during early follow-up of invasive cervical cancer.
AB  - Considering the limitations of cytology for detection of residual cervical cancer
      after radiotherapy, the aim of this study was to evaluate the frequency and viral
      load of high-risk HPV in cervical and vaginal samples during the early follow-up
      of patients treated for invasive cervical cancer and correlate the results with
      cytological examination. Conventional cytology and hybrid capture test were
      performed on cervical and vaginal samples of 52 women with invasive cervical
      carcinoma 3 months after therapy. High-risk HPV was detected in 46.1% of the
      samples and the median and the range of the ratio relative light unit
      (RLU)/cutoff (CO) (estimated viral load) in positive samples was 1.71 (1
      2120.03). No significant difference was observed in viral frequency and in median
      of the ratio RLU/CO between samples of patients at different stages (I-III) and
      between cervical samples, from patients treated by exclusive radiotherapy with or
      without chemotherapy, and vaginal samples, from patients who underwent to
      hysterectomy and radiotherapy with or without chemotherapy. Cytological
      abnormalities were more frequent significantly in samples with HPV than in
      samples without HPV. The viral load was also higher significantly in samples with
      cytological abnormalities when compared with the samples without cytological
      abnormalities. In conclusion, HPV detection methods may be useful during the
      early follow-up as a complement to conventional cytology for the diagnosis of
      residual cervical cancer after radiotherapy.

PMID- 22585731
TI  - Human T-lymphotropic virus type I (HTLV-I)-specific CD8+ cells accumulate in the
      lungs of patients infected with HTLV-I with pulmonary involvement.
AB  - Pulmonary involvement has been identified in human T-lymphotropic virus type I
      (HTLV-I) carriers and patients with HTLV-I-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP). However, the relationship between HTLV-I infection and
      lung disease is poorly understood. The occurrence of HTLV-I-specific immune
      responses in the lungs of patients infected with HTLV-I with pulmonary
      involvement was investigated. The frequency of HTLV-I-specific CD8+ cells and the
      amount of HTLV-I proviral DNA were determined in bronchoalveolar lavage fluid
      cells and peripheral blood mononuclear cells (PBMCs) from five patients with
      HAM/TSP and one HTLV-I carrier who had pulmonary involvement. HTLV-I-specific
      CD8+ cells were detected by flow cytometry using human leukocyte antigen/antigen
      complex multimers. The analysis of bronchoalveolar lavage fluid revealed
      lymphocytosis in five of six patients. HTLV-I provirus was detected in the
      bronchoalveolar lavage fluid cells of all patients, and the proviral load in
      these cells was comparable to that in PBMCs. The frequency of HTLV-I-specific
      CD8+ cells in the bronchoalveolar lavage fluid cells was 5.1 times higher than
      that in PBMCs. Immunohistochemically, clusters formed by HTLV-I-specific CD8+
      cells were detected in lung tissue by in situ tetramer staining. No samples were
      available from patients infected with HTLV-I without lung disorders. Whether
      accumulation of CD8+ cells is specific to patients with pulmonary involvement
      remains unclear. These results indicate that HTLV-I-specific CD8+ cells
      accumulate and HTLV-I-infected cells exist in the lungs of patients infected with
      HTLV-I with pulmonary involvement.

PMID- 22585732
TI  - Do neutralizing antibody responses generated by human papillomavirus infections
      favor a better outcome of low-grade cervical lesions?
AB  - To determine the role of neutralizing antibody generated by human papillomavirus
      (HPV) infections, baseline levels of serum neutralizing antibodies directed
      against HPV 16 and cervical HPV DNA were determined in 242 unvaccinated women
      with low-grade cervical abnormalities, who were then monitored by cytology and
      colposcopy every 4 months. In women infected with HPV 16 (n = 42), abnormal
      cytology persisted longer in those positive for HPV 16-specific neutralizing
      antibodies at baseline (median time to cytological regression: 23.8 vs. 7.2
      months). Progression to cervical precancer (cervical intraepithelial neoplasia
      grade 3) within 5 years occurred only among women carrying HPV 16-specific
      neutralizing antibodies (P = 0.03, log-rank test). In women infected with types
      other than HPV 16 (n = 200), detection of HPV 16-specific neutralizing antibodies
      was not correlated with disease outcome. In conclusion, development of specific
      neutralizing antibodies following natural HPV 16 infection did not favor a better
      outcome of low-grade cervical lesions induced by HPV 16 or by other types;
      rather, detection of neutralizing antibodies generated by current infection may
      reflect viral persistence and thus help identify those who are at high risk of
      disease progression.

PMID- 22585733
TI  - Rhinovirus load and disease severity in children with lower respiratory tract
      infections.
AB  - It has not been clarified if there is a correlation between rhinovirus (RV) load
      and disease severity in the lower respiratory tract infections of hospitalized
      children. This study was undertaken to elucidate the contribution of the viral
      load to the development of disease severity in 412 children <=3 years of age who
      were hospitalized with lower respiratory tract infections. The RV load in
      nasopharyngeal aspirates obtained from the patients at the time of admission was
      measured by real-time quantitative reverse-transcription polymerase chain
      reaction (PCR), and the clinical symptoms of the patients were assessed using a
      severity scoring system. Of the 412 patients, 43 (10.4%) were diagnosed with RV
      infections only, and 15 were determined to have high severity scores. When all
      patients infected with RV were assessed, there was no correlation between the
      viral load and the disease severity. However, there was a significant negative
      correlation between the disease severity and age among children <11 months of age
      (n = 15, rho = -0.677, P = 0.006) and a significant positive correlation between
      the viral load and the disease severity among children >=11 months of age (n =
      28, rho = 0.407, P = 0.032). Among the patients infected with RV <11 months of
      age, the disease severity may be associated with an immature immune response and
      the small diameter of their airways rather than viral load. By contrast, in the
      patients >=11 months of age, viral load may contribute to the development of
      disease severity.

PMID- 22585734
TI  - Association of HPV infection and Chlamydia trachomatis seropositivity in cases of
      cervical neoplasia in Midwest Brazil.
AB  - High-risk human papillomavirus (HPV) is considered the main etiological agent for
      cervical neoplasia. However, the presence of a single type HPV infection alone is
      unlikely to be sufficient to cause cervical cancer. There is epidemiologic
      evidence suggesting that HPV and Chlamydia trachomatis play a central role in the
      etiology of cervical intraepithelial neoplasia and subsequent cervical cancer. To
      evaluate the HPV prevalence and the seropositivity for C. trachomatis in women
      referred to the colposcopy clinic due to an abnormal cervical smear and to
      examine the effect of this association on the severity of cervical neoplasia.
      Following enrollment, 131 patients underwent colposcopy and biopsies when
      necessary. HPV DNA was detected by the polymerase chain reaction (PCR) and
      genotyping was performed by reverse line-blot hybridization assay. C. trachomatis
      seropositivity was tested by ELISA for the detection of IgG antibodies. The
      prevalence of HPV infection was 86.3%. Seropositivity for C. trachomatis was 26%.
      Thirty-one women (27.4%) were positive for C. trachomatis antibodies and HPV-DNA.
      The most prevalent HPV type in C. trachomatis-seropositive women were HPV 16
      (51.6%) and this HPV type was present mainly in neoplasia cases. Positivity for
      HPV, particularly HPV types 16 and 18, and C. trachomatis seropositivity was
      significantly associated with a diagnosis of high grade neoplasia. Borderline
      significance was observed after adjustment for HPV. C. trachomatis seropositivity
      is associated with high grade neoplasia in women infected with HPV, mainly when
      the types 16 and 18 were involved.

PMID- 22585735
TI  - Spatiotemporally separated antigen uptake by alveolar dendritic cells and airway
      presentation to T cells in the lung.
AB  - Asthma pathogenesis is focused around conducting airways. The reasons for this
      focus have been unclear because it has not been possible to track the sites and
      timing of antigen uptake or subsequent antigen presentation to effector T cells.
      In this study, we use two-photon microscopy of the lung parenchyma and note
      accumulation of CD11b(+) dendritic cells (DCs) around the airway after allergen
      challenge but very limited access of these airway-adjacent DCs to the contents of
      the airspace. In contrast, we observed prevalent transepithelial uptake of
      particulate antigens by alveolar DCs. These distinct sites are temporally linked,
      as early antigen uptake in alveoli gives rise to DC and antigen retention in the
      airway-adjacent region. Antigen-specific T cells also accumulate in the airway
      adjacent region after allergen challenge and are activated by the accumulated
      DCs. Thus, we propose that later airway hyperreactivity results from selective
      retention of allergen-presenting DCs and antigen-specific T cells in airway
      adjacent interaction zones, not from variation in the abilities of individual DCs
      to survey the lung.

PMID- 22585736
TI  - Cannabinoids suppress inflammatory and neuropathic pain by targeting alpha3
      glycine receptors.
AB  - Certain types of nonpsychoactive cannabinoids can potentiate glycine receptors
      (GlyRs), an important target for nociceptive regulation at the spinal level.
      However, little is known about the potential and mechanism of glycinergic
      cannabinoids for chronic pain treatment. We report that systemic and intrathecal
      administration of cannabidiol (CBD), a major nonpsychoactive component of
      marijuana, and its modified derivatives significantly suppress chronic
      inflammatory and neuropathic pain without causing apparent analgesic tolerance in
      rodents. The cannabinoids significantly potentiate glycine currents in dorsal
      horn neurons in rat spinal cord slices. The analgesic potency of 11 structurally
      similar cannabinoids is positively correlated with cannabinoid potentiation of
      the alpha3 GlyRs. In contrast, the cannabinoid analgesia is neither correlated
      with their binding affinity for CB1 and CB2 receptors nor with their psychoactive
      side effects. NMR analysis reveals a direct interaction between CBD and S296 in
      the third transmembrane domain of purified alpha3 GlyR. The cannabinoid-induced
      analgesic effect is absent in mice lacking the alpha3 GlyRs. Our findings suggest
      that the alpha3 GlyRs mediate glycinergic cannabinoid-induced suppression of
      chronic pain. These cannabinoids may represent a novel class of therapeutic
      agents for the treatment of chronic pain and other diseases involving GlyR
      dysfunction.

PMID- 22585737
TI  - PTK7 as a novel marker for favorable gastric cancer patient survival.
AB  - BACKGROUND AND OBJECTIVES: Protein tyrosine kinase 7 (PTK7) plays important
      functions in several cancer types but its expression in gastric cancer remains
      unknown. This study was designed to investigate PTK7 expression in gastric
      cancer. METHODS: PTK7 expression was assessed by immunohistochemistry in 201
      gastric cancer patients. The relationship between PTK7 expression and
      clinicopathological features and patients prognosis were statistically analyzed.
      RESULTS: PTK7 expression was detected in 56.72% (114 of 201) of gastric cancer
      patients. The immunostaining was predominantly localized in the cytoplasm. The
      statistical analyses showed that PTK7 expression was more frequently detected in
      patients with well-differentiated tumors (P = 0.001). Furthermore, PTK7
      expression was significantly related to the favorable overall survival (OS; P =
      0.012) and disease-free survival (DFS; P = 0.009). Multivariate Cox regression
      analyses revealed that PTK7 expression was an independent prognostic factor for
      both favorable OS (P = 0.028) and DFS (P = 0.012). CONCLUSION: Our findings
      demonstrate that PTK7 can serve as a novel prognostic biomarker for gastric
      cancer patients.

PMID- 22585738
TI  - Biallelic inactivation of NF1 in a sporadic plexiform neurofibroma.
AB  - Plexiform neurofibromas are a major cause of morbidity in individuals with
      neurofibromatosis type 1 (NF1). Sporadically, these tumors appear as an isolated
      feature without other signs of NF1. A role for the NF1 gene in solitary plexiform
      neurofibromas has never been described. In this study, we report a 13-year-old
      boy who was diagnosed with a plexiform neurofibroma, without other NF1 diagnostic
      criteria. The tumor was partially resected and analyzed using different
      techniques: karyotyping, fluorescence in situ hybridization (FISH), and
      microarray comparative genomic hybridization (aCGH). Tumor Schwann cell culture
      and subsequent karyotyping showed a rearrangement involving chromosomes 1 and 17,
      namely an insertion of chromosomal bands 1p36-35 at 17q11.2. FISH demonstrated
      that the insertion interrupted the NF1 gene. In addition, a deletion was detected
      affecting the other NF1 allele. Whole-genome aCGH analysis of the resected tumor
      confirmed the presence of an 8.28 Mb deletion including the NF1 gene locus in ~15
      20% of tumor cells. We conclude that biallelic NF1 inactivation was at the origin
      of the isolated plexiform neurofibroma in this patient. The insertion is most
      likely the "first hit" and the large deletion the "second hit."

PMID- 22585739
TI  - Wiskott-Aldrich syndrome protein (WASp) and N-WASp are involved in the regulation
      of NK-cell migration upon NKG2D activation.
AB  - NKG2D is a transmembrane receptor mainly expressed on CD8(+)  T cells and NK
      cells. Engagement of NKG2D with its ligands can trigger a cytotoxic response. It
      has been shown that tumor cells deliver soluble NKG2D ligands as a mechanism of
      immune evasion through the downregulation of surface-expressed NKG2D. These
      ligands may be also secreted in microvesicles and regulate NK-cell function, but
      the existence of alternative mechanisms has not been explored. In this study, we
      describe that NKG2D activation inhibits NK-cell chemotaxis toward a CXCL12
      gradient. Costimulation of the inhibitory receptor NKG2A rescues NK-cell
      migration rates. Thus, the balance of NKG2D/NKG2A activation may determine the
      migratory ability of NK cells. Furthermore, our data indicated that NKG2D cross
      linking induces the activation of the Rho GTPases Rac1 and Cdc42, while RhoA
      activity is decreased. Pharmacological inhibition of the Cdc42 effectors Wiskott
      Aldrich syndrome protein (WASp)/N-WASp, and the reduction of their levels using
      RNA interference partially abolished NKG2D-mediated impairment of cell migration,
      suggesting a pivotal role of Cdc42 in the regulation of NK-cell migration by
      NKG2D activation. Therefore, our results provide a new mechanism that may
      contribute to the immune response or evasion in tumors.

PMID- 22585740
TI  - The effectiveness and safety of triple-antiplatelet treatment based on cilostazol
      for patients receiving percutaneous coronary intervention: a meta-analysis.
AB  - The combination of cilostazol, aspirin, and clopidogrel (triple therapy) after
      percutaneous coronary intervention has been considered as an alternative therapy.
      We performed a meta-analysis based on 8 randomized controlled trials with a total
      of 3332 patients to compare the effectiveness and safety of this triple therapy
      with traditional dual therapy (aspirin and clopidogrel). Our findings suggested
      that the triple therapy is more effective than dual therapy in preventing
      restenosis (odds ratio [OR]: 0.52, 95% confidence interval [CI]: 0.40-0.66, P <
      0.00001), maintaining minimal lumen diameter (OR: 0.15, 95% CI: 0.10-0.20, P <
      0.00001), and avoiding target-vessel revascularization (OR: 0.62, 95% CI: 0.47
      0.82, P = 0.001). There is also no significant difference in major adverse
      cardiac and cerebrovascular events between the 2 therapies, except the smaller
      occurrence rate of target-lesion revascularization in the triple-therapy group
      (OR: 0.42, 95% CI: 0.26-0.69, P = 0.0005). However, the triple therapy is
      associated with a higher level of adverse drug events, including rash (OR: 2.45,
      95% CI: 1.41-4.23, P = 0.001), gastrointestinal disorders (OR: 2.59, 95% CI: 1.26
      5.30, P = 0.009), and drug discontinuation (OR: 3.80, 95% CI: 1.59-9.10, P =
      0.003), but it has no difference in bleeding compared with the dual therapy (OR:
      1.05, 95% CI: 0.71-1.55, P = 0.80).

PMID- 22585741
TI  - Discordant monozygotic twins for macrocephaly-capillary malformation.

PMID- 22585742
TI  - Validity of frozen section in sentinel lymph node biopsy for the staging in oral
      and oropharyngeal squamous cell carcinoma.
AB  - BACKGROUND AND OBJECTIVES: The potential of avoiding a secondary surgery for
      therapeutic neck dissection (TND) by sentinel node (SN) positivity makes the
      intraoperative evaluation of SNs an attractive option. The aim of this study was
      to analyze accuracy of intraoperative frozen section (FS) for detection of occult
      metastases in a large single institutional patient cohort undergoing SN-biopsy.
      METHODS: Between 2000 and 2010, 92 consecutive patients with early stage
      oropharyngeal squamous cell carcinoma (OSCC) (cT1/cT2/cN0) were prospectively
      enrolled. Detection rate of occult metastases by monoslice FS was compared with
      the definitive histopathologic work up by step serial sectioning (SSS) and
      immunohistochemistry (IHC). In case of SN-positivity on FS TND was performed in
      the same narcosis. RESULTS: 15/92 patients revealed positive SNs by FS compared
      to 34/92 after SSS and IHC. Sensitivity, NPV and FNR for the detection of all
      sizes of metastases by FS was 47, 77, and 52%, for isolated tumor cells (ITC) 8,
      86, 92%, for micrometastases 43, 90, 57%, and for macrometastases 93, 98, 7%.
      CONCLUSION: Sensitivity of FS by the monoslice depends on the metastases size and
      allows a single-stage procedure in half of the SN-positive patients. To improve
      sensitivity for small tumor deposits either a multislice-technique or molecular
      methods are needed.

PMID- 22585743
TI  - Reduced fractional anisotropy in the uncinate fasciculus in patients with major
      depression carrying the met-allele of the Val66Met brain-derived neurotrophic
      factor genotype.
AB  - Experimental studies support a neurotrophic hypothesis of major depressive
      disorder (MDD). The aim of this study was to determine the effect of Val66Met
      brain-derived neurotrophic factor (BDNF) polymorphism on the white matter fiber
      tracts connecting hippocampus and amygdala with the prefrontal lobe in a sample
      of patients with MDD and healthy controls. Thirty-seven patients with MDD and 42
      healthy volunteers were recruited. Diffusion tensor imaging (DTI) data with 61
      diffusion directions were obtained with MRI 3 Tesla scanner. Deterministic
      tractography was applied with ExploreDTI and Val66Met BDNF SNP (rs6265) was
      genotyped. Fiber tracts connecting the hippocampus and amygdala with the
      prefrontal lobe, namely uncinate fasciculus (UF), fornix, and cingulum were
      analyzed. A significant interaction was found in the UF between BDNF alleles and
      diagnosis. Patients carrying the BDNF met-allele had smaller fractional
      anisotropy (FA) in the UF compared to those patients homozygous for val-allele
      and compared to healthy subjects carrying the met-allele. A significant three-way
      interaction was detected between region of the cingulum (dorsal, rostral, and
      parahippocampal regions), brain hemisphere and BDNF genotype. Larger FA was
      detectable in the left rostral cingulum for met-allele carriers when compared to
      val/val alelle carriers. We provide evidence for the importance of the
      neurotrophic involvement in limbic and prefrontal connections. The met-allele of
      the BDNF polymorphism seems to render subjects more vulnerable for dysfunctions
      associated with the UF, a tract known to be related to negative emotional
      cognitive processing bias, declarative memory problems, and autonoetic self
      awareness.

PMID- 22585744
TI  - CD73 as a novel prognostic biomarker for human colorectal cancer.

PMID- 22585745
TI  - Abstracts of the Teratology Society 52nd Annual Meeting, June 23-27, 2012,
      Baltimore, MD.

PMID- 22585747
TI  - AFM feature definition for neural cells on nanofibrillar tissue scaffolds.
AB  - A diagnostic approach is developed and implemented that provides clear feature
      definition in atomic force microscopy (AFM) images of neural cells on
      nanofibrillar tissue scaffolds. Because the cellular edges and processes are on
      the same order as the background nanofibers, this imaging situation presents a
      feature definition problem. The diagnostic approach is based on analysis of
      discrete Fourier transforms of standard AFM section measurements. The diagnostic
      conclusion that the combination of dynamic range enhancement with low-frequency
      component suppression enhances feature definition is shown to be correct and to
      lead to clear-featured images that could change previously held assumptions about
      the cell-cell interactions present. Clear feature definition of cells on
      scaffolds extends the usefulness of AFM imaging for use in regenerative medicine.

PMID- 22585748
TI  - Quantifying ATP turnover in anoxic coleoptiles of rice (Oryza sativa)
      demonstrates preferential allocation of energy to protein synthesis.
AB  - Oxygen deprivation limits the energy available for cellular processes and yet no
      comprehensive ATP budget has been reported for any plant species under O(2)
      deprivation, including Oryza sativa. Using 3-d-old coleoptiles of a cultivar of
      O. sativa tolerant to flooding at germination, (i) rates of ATP regeneration in
      coleoptiles grown under normoxia (aerated solution), hypoxia (3% O(2)), and
      anoxia (N(2)) and (ii) rates of synthesis of proteins, lipids, nucleic acids, and
      cell walls, as well as K(+) transport, were determined. Based on published
      bioenergetics data, the cost of synthesizing each class of polymer and the
      proportion of available ATP allocated to each process were then compared. Protein
      synthesis consumed the largest proportion of ATP synthesized under all three
      oxygen regimes, with the proportion of ATP allocated to protein synthesis in
      anoxia (52%) more than double that in normoxic coleoptiles (19%). Energy
      allocation to cell wall synthesis was undiminished in hypoxia, consistent with
      preferential elongation typical of submerged coleoptiles. Lipid synthesis was
      also conserved strongly in O(2) deficits, suggesting that membrane integrity was
      maintained under anoxia, thus allowing K(+) to be retained within coleoptile
      cells. Rates of protein synthesis in coleoptiles from rice cultivars with
      contrasting tolerance to oxygen deficits (including mutants deficient in
      fermentative enzymes) confirmed that synthesis and turnover of proteins always
      accounted for most of the ATP consumed under anoxia. It is concluded that
      successful establishment of rice seedlings under water is largely due to the
      capacity of coleoptiles to allocate energy to vital processes, particularly
      protein synthesis.

PMID- 22585749
TI  - Blood glucose determination: plasma or serum?
AB  - BACKGROUND: Blood glucose determination is one of the most common clinical
      diagnostic tests. Often, blood is collected in a field station and analysis is
      carried out in a remote laboratory. Because blood cells can continue to
      metabolize glucose, the time of determination of blood glucose after drawing the
      blood is important. METHOD: In order to test the relative suitability of plasma
      and serum for blood glucose determination, fluoride plasma and Ethylene Diamine
      Tetra Acetic acid (EDTA) plasma were compared with the serum of the same patient.
      The analyses were carried out within 10 min of drawing the blood and, thereafter,
      with a gap of 4 hr and 8 hr. RESULTS: Serum gave values lower than fluoride
      plasma by 1.15%. Although this difference was statistically significant, it may
      not be physiologically relevant. Hence, serum may be used for blood glucose
      determination with an error of 1.15%. On storing the sample at room temperature
      for 8 hr, the serum glucose value decreased by 8%. Even fluoride plasma had 4.3%
      lower glucose. CONCLUSION: Hence, blood glucose should be determined within as
      short a time as possible after drawing the blood.

PMID- 22585750
TI  - CcpA and three newly identified proteins are involved in biofilm development in
      Lactobacillus plantarum.
AB  - The aim of this study was to identify genes involved in biofilm development in
      the probiotic lactic acid bacterium Lactobacillus plantarum. The ability of L.
      plantarum LM3 and of some derivative mutant strains to form biofilm has been
      investigated. Biofilm microtitre plate assays showed that L. plantarum LM3-2,
      carrying a null mutation in the ccpA gene, coding the CcpA master regulator, was
      partially impaired in biofilm production compared to wild type (LM3). Moreover,
      we found three genes in the L. plantarum genome, hereby named flmA, flmB, and
      flmC, whose deduced amino acid sequences show significant identity with the
      Streptococcus mutans BrpA (biofilm regulatory protein A). We investigated the
      role of FlmA, FlmB, and FlmC in biofilm formation by isolating strains carrying
      null mutations in the corresponding genes. Our results suggest involvement of the
      Flm proteins in biofilm development. Moreover, transcriptional studies show that
      expression of flmA, flmB, and flmC is under the control of CcpA. These results,
      together with the reduced ability of LM3-2 (ccpA1) to form biofilm, strongly
      suggest a positive role of the master regulator CcpA in biofilm development.

PMID- 22585751
TI  - A quantitative proteomic analysis of lung epithelial (A549) cells infected with
      2009 pandemic influenza A virus using stable isotope labelling with amino acids
      in cell culture.
AB  - Influenza A virus is one of the world's major uncontrolled pathogens, causing
      seasonal epidemics as well as global pandemics. This was evidenced by the recent
      emergence and now prevalence of the 2009 swine origin pandemic H1N1 influenza A
      virus. In this study, quantitative proteomics using stable isotope labelling with
      amino acids in cell culture was used to investigate the changes in the host cell
      proteome in cells infected with pandemic H1N1 influenza A virus. The study was
      conducted in A549 cells that retain properties similar to alveolar cells. Several
      global pathways were affected, including cell cycle regulation and lipid
      metabolism, and these could be correlated with recent microarray analyses of
      cells infected with influenza A virus. Taken together, both quantitative
      proteomics and transcriptomic approaches can be used to identify potential
      cellular proteins whose functions in the virus life cycle could be targeted for
      chemotherapeutic intervention.

PMID- 22585752
TI  - Anthropologists as cognitive scientists.
AB  - Anthropology combines two quite different enterprises: the ethnographic study of
      particular people in particular places and the theorizing about the human
      species. As such, anthropology is part of cognitive science in that it
      contributes to the unitary theoretical aim of understanding and explaining the
      behavior of the animal species Homo sapiens. This article draws on our own
      research experience to illustrate that cooperation between anthropology and the
      other sub-disciplines of cognitive science is possible and fruitful, but it must
      proceed from the recognition of anthropology's unique epistemology and
      methodology.

PMID- 22585757
TI  - Cognitive anthropological fieldwork.
AB  - In their introduction, Beller et al. point to important issues regarding the
      problematic interaction of anthropology and cognitive sciences (CS). I address
      some of these issues in stressing first some limitations of the current state of
      the fields of anthropology and CS. In the second half of this article, using data
      from studies I have been conducting among the Yucatec Mayas (Mexico), I present
      some concrete cases where anthropological and CS methods and approaches are
      complementary. Finally, I propose some solutions to find common ground and ways
      to improve cross-disciplinary collaboration.

PMID- 22585758
TI  - Journals on the move: launch of the ESC Journals app.

PMID- 22585760
TI  - Should the study of Homo sapiens be part of cognitive science?
AB  - Beller, Bender, and Medin argue that a reconciliation between anthropology and
      cognitive science seems unlikely. We disagree. In our view, Beller et al.'s view
      of the scope of what anthropology can offer cognitive science is too narrow. In
      focusing on anthropology's role in elucidating cultural particulars, they
      downplay the fact that anthropology can reveal both variation and universals in
      human cognition, and is in a unique position to do so relative to the other
      subfields of cognitive science. Indeed, without cross-cultural research, the
      universality of any aspect of human cognition cannot truly be established.
      Therefore, if the goal of cognitive science is to understand the cognitive
      capacities of our species as a whole, then it cannot do without anthropology. We
      briefly review a growing body of anthropological work aimed at answering
      questions about human cognition and offer suggestions for future work.

PMID- 22585759
TI  - Loss of E protein transcription factors E2A and HEB delays memory-precursor
      formation during the CD8+ T-cell immune response.
AB  - The transcription factors E2A and HEB (members of the E protein family) have been
      shown to play essential roles in lymphocyte development, while their negative
      regulators, the Id proteins, have been implicated in both lymphocyte development
      and in the CD8(+)  T-cell immune response. Here, we show that E proteins also
      influence CD8(+)  T cells responding to infection. E protein expression was
      upregulated by CD8(+)  T cells during the early stages of infection and increased
      E protein DNA-binding activity could be detected upon TCR stimulation. Deficiency
      in the E proteins, E2A and HEB, led to increased frequency of terminally
      differentiated effector KLRG1(hi)  CD8(+)  T cells in mice during infection, and
      decreased generation of longer-lived memory-precursor cells during the immune
      response. These data suggest a model whereby E protein transcription factor
      activity favors rapid memory-precursor T-cell formation while their negative
      regulators, Id2 and Id3, are both required for robust effector CD8(+)  T-cell
      response during infection.

PMID- 22585761
TI  - Characteristics of pediatric traditional Chinese medicine users in Taiwan: a
      nationwide cohort study.
AB  - BACKGROUND AND OBJECTIVES: Traditional chinese medicine (TCM) is one of the most
      commonly used complementary and alternative medicines. However, there is a
      paucity of epidemiologic reports on features of pediatric TCM users. As TCM
      services are fully reimbursed by National Health Insurance in Taiwan, this study
      used a nationwide cohort database to investigate demographics, diseases patterns,
      and parents' characteristics of pediatric TCM users. METHODS: Children aged <12
      years were extracted from the National Health Insurance Research Database for
      analysis. These pediatric TCM users' demographics, medical conditions, and
      reasons for medical services were compared with users of Western medicine by
      Poisson regression. Children who did not use any medical services were excluded.
      RESULTS: Of 107,337 children who were enrolled and followed up in 2005, 19,669
      children (18.3%) used TCM. Compared with Western medicine-only users, school-age
      children (aged 6-12 years), preschool age children (3-5 years), and toddlers (1-2
      years) were more likely to use TCM than infants (<1 year; rate ratio = 4.47, 3.66
      and 2.59, respectively; P < .001 for all). Parental factors were associated with
      more TCM use, including female gender, age >35 years, past experience with TCM,
      and higher income levels. Allergic reactions and respiratory tract,
      gastrointestinal tract, and musculoskeletal problems were also associated with
      higher TCM use. CONCLUSIONS: The use of TCM was correlated with both patient and
      parental factors, among which children's age and parental TCM use were the most
      prominent. Additional studies on the efficacy of TCM are warranted.

PMID- 22585762
TI  - The initiative for innovation in pediatric education: a snapshot of a program
      evaluation.

PMID- 22585763
TI  - Pediatric battery-related emergency department visits in the United States, 1990
      2009.
AB  - OBJECTIVE: To investigate the epidemiology of battery-related emergency
      department (ED) visits among children <18 years of age in the United States.
      METHODS: Using a nationally representative sample from the National Electronic
      Injury Surveillance System, battery-related ED visits in the United States from
      1990 to 2009 were analyzed. Four battery exposure routes for patients were
      determined from diagnosis codes and case narratives: ingestion, mouth exposure,
      ear canal insertion, and nasal cavity insertion. RESULTS: An estimated 65788 (95%
      confidence interval: 54498-77078) patients <18 years of age presented to US EDs
      due to a battery-related exposure during the 20-year study period, averaging 3289
      battery-related ED visits annually. The average annual battery-related ED visit
      rate was 4.6 visits per 100000 children. The number (P < .001) and rate (P =
      .002) of visits increased significantly during the study period, with substantial
      increases during the last 8 study years. The mean age was 3.9 years (95%
      confidence interval: 3.5-4.2), and 60.2% of patients were boys. Battery ingestion
      accounted for 76.6% of ED visits, followed by nasal cavity insertion (10.2%),
      mouth exposure (7.5%), and ear canal insertion (5.7%). Button batteries were
      implicated in 83.8% of patient visits caused by a known battery type. Most
      children (91.8%) were treated and released from the ED. CONCLUSIONS: This study
      evaluated battery-related ED visits among US children using a nationally
      representative sample. Batteries pose an important hazard to children, especially
      those <= 5 years of age. The increasing number and rate of battery-related ED
      visits among children underscore the need for increased prevention efforts.

PMID- 22585764
TI  - An interdisciplinary initiative to reduce unplanned extubations in pediatric
      critical care units.
AB  - OBJECTIVE: Unplanned extubations in pediatric critical care units can result in
      increased mortality, morbidity, and length of stay. We sought to reduce the
      incidence of these events by reliably measuring occurrences and instituting a
      series of coordinated interdisciplinary interventions. METHODS: This was an
      internal review board-approved quality improvement project. Data were
      prospectively collected from the electronic medical record, and analyzed over 24
      months (January 1, 2009-December 2010), and divided into 3 periods: baseline (9
      months), intervention with multiple rapid improvement cycles (8 months), and
      postintervention (7 months). Interventions included standardization of
      endotracheal tube taping practices upon admission, improved patient handoffs,
      systematic review of unplanned events, reexamination of sedation practices, and
      promotion of transparency of performance measures. RESULTS: The PICU experienced
      21 events in the 9 months before the initiative, 13 events over the 8-month
      intervention period, and 5 events in the 7-month postintervention period. The
      cardiac intensive care unit (CICU) experienced 11, 4, and 0 events, respectively.
      Mean event rates per 100 patient days for each interval were 0.80, 0.50, and 0.29
      for the PICU and 0.74, 0.44, and 0 for the CICU. Monthly event rates for the CICU
      were significantly different by using the Kruskal-Wallis test (P < .05) but not
      for the PICU (P = .36) CONCLUSIONS: Through accurate tracking, multiple practice
      changes, and promoting transparency of efforts and data, an interdisciplinary
      team reduced the number of unplanned extubations in both ICUs. This reduction has
      been sustained throughout the postintervention monitoring period.

PMID- 22585766
TI  - Postsecondary education and employment among youth with an autism spectrum
      disorder.
AB  - OBJECTIVES: We examined the prevalence and correlates of postsecondary education
      and employment among youth with an autism spectrum disorder (ASD). METHODS: Data
      were from a nationally representative survey of parents, guardians, and young
      adults with an ASD. Participation in postsecondary employment, college, or
      vocational education and lack of participation in any of these activities were
      examined. Rates were compared with those of youth in 3 other eligibility
      categories: speech/language impairment, learning disability, and mental
      retardation. Logistic regression was used to examine correlates of each outcome.
      RESULTS: For youth with an ASD, 34.7% had attended college and 55.1% had held
      paid employment during the first 6 years after high school. More than 50% of
      youth who had left high school in the past 2 years had no participation in
      employment or education. Youth with an ASD had the lowest rates of participation
      in employment and the highest rates of no participation compared with youth in
      other disability categories. Higher income and higher functional ability were
      associated with higher adjusted odds of participation in postsecondary employment
      and education. CONCLUSIONS: Youth with an ASD have poor postsecondary employment
      and education outcomes, especially in the first 2 years after high school. Those
      from lower-income families and those with greater functional impairments are at
      heightened risk for poor outcomes. Further research is needed to understand how
      transition planning before high school exit can facilitate a better connection to
      productive postsecondary activities.

PMID- 22585765
TI  - A double-blind, placebo-controlled trial of omega-3 fatty acids in Tourette's
      disorder.
AB  - OBJECTIVE: Clinical observations have suggested therapeutic effects for omega-3
      fatty acids (O3FA) in Tourette's disorder (TD), but no randomized, controlled
      trials have been reported. In a placebo-controlled trial, we examined the
      efficacy of O3FA in children and adolescents with TD. METHODS: Thirty-three
      children and adolescents (ages 6-18) with TD were randomly assigned, double
      blind, to O3FA or placebo for 20 weeks. O3FA consisted of combined
      eicosapentaenoic acid and docosahexaenoic acid. Placebo was olive oil. Groups
      were compared by using (1) intent-to-treat design, with the last-observation
      carried-forward controlling for baseline measures and attention
      deficit/hyperactivity disorder via (a) logistic regression, comparing percentage
      of responders on the primary Yale Global Tic Severity Scale (YGTSS)-Tic and
      secondary (YGTSS-Global and YGTSS-Impairment) outcome measures and (b) analysis
      of covariance; and (2) longitudinal mixed-effects models. RESULTS: At end point,
      subjects treated with O3FA did not have significantly higher response rates or
      lower mean scores on the YGTSS-Tic (53% vs 38%; 15.6 +/- 1.6 vs 17.1 +/- 1.6, P >
      .1). However, significantly more subjects on O3FA were considered responders on
      the YGTSS-Global measure (53% vs 31%, P = .05) and YGTSS-Impairment measure (59%
      vs 25%, P < .05), and mean YGTSS-Global scores were significantly lower in the
      O3FA-treated group than in the placebo group (31.7 +/- 2.9 vs 40.9 +/- 3.0, P =
      .04). Obsessive-compulsive, anxiety, and depressive symptoms were not
      significantly affected by O3FA. Longitudinal analysis did not yield group
      differences on any of the measures. CONCLUSIONS: O3FA did not reduce tic scores,
      but it may be beneficial in reduction of tic-related impairment for some children
      and adolescents with TD. Limitations include the small sample and the possible
      therapeutic effects of olive oil.

PMID- 22585767
TI  - Randomized trial of sumatriptan and naproxen sodium combination in adolescent
      migraine.
AB  - BACKGROUND: Treatment of adolescent migraine remains a significant unmet medical
      need. We compared the efficacy and safety of 3 doses of sumatriptan and naproxen
      sodium (suma/nap) combination tablets to placebo in the acute treatment of
      adolescent migraine. METHODS: This randomized, parallel group study in 12 to 17
      year olds required 2 to 8 migraines per month (typically lasting >3 hours
      untreated) for >= 6 months. Subjects entered a 12-week run-in phase, treating 1
      moderate-to-severe migraine (attack 1) with single-blind placebo. Subjects
      reporting headache pain 2 hours after dosing were randomly assigned into a 12
      week double-blind phase, treating 1 moderate-to-severe migraine (attack 2) with
      placebo (n = 145), suma/nap 10/60 mg (n = 96), 30/180 mg (n = 97), or 85/500 mg
      (n = 152). The primary end point was the percentage of subjects pain-free at 2
      hours. RESULTS: The attack 2 adjusted (age; baseline pain severity) 2-hour pain
      free rates were higher with suma/nap 10/60 mg (29%; adjusted P = .003), 30/180 mg
      (27%; adjusted P = .003), and 85/500 mg (24%; adjusted P = .003) versus placebo
      (10%). Posthoc primary end-point analyses did not demonstrate differences among
      the 3 doses or an age-by-treatment interaction. Statistically significant
      differences were found for 85/500 mg versus placebo for sustained pain-free 2 to
      24 hours (23% vs 9%; adjusted P = .008), 2-hour photophobia-free (59% vs 41%;
      adjusted P = .008), and 2-hour phonophobia-free (60% vs 42%; adjusted P = .008).
      Analyses of other pain, associated symptoms, rescue medication use, and health
      outcome end points supported higher efficacy for active doses versus placebo. All
      active doses were well tolerated. CONCLUSIONS: All doses of suma/nap were well
      tolerated, providing similarly effective acute treatment of adolescent migraine
      pain and associated symptoms, as compared with placebo.

PMID- 22585768
TI  - Lipid profiles of children with Down syndrome compared with their siblings.
AB  - OBJECTIVES: Our objective was to compare serum lipid profiles, total cholesterol
      (TC), low-density lipoprotein (LDL), triglycerides (TG), and high-density
      lipoprotein (HDL) between children with Down syndrome (DS) and their non-DS
      siblings. We hypothesized that the children with DS would have higher TC, LDL,
      and TG and lower HDL. The secondary aim was to explore if the difference in lipid
      profiles could be explained by differences in weight status. METHODS: This was a
      cross-sectional study. Fasting lipid profile was obtained from 27 children with
      DS and 31 siblings between 4 and 10 years of age with no severe comorbidities
      (heart disease, cancer, hypothyroidism, diabetes, or obesity). BMI was calculated
      and BMI z scores were used to account for differences in BMI throughout
      childhood. RESULTS: Children with DS had higher TC (difference, 11.2 mg/dL; 95%
      confidence interval: 2.5-19.9; P = .01), LDL (12.8 mg/dL; 7.2-18.4; P < .001), TG
      (33.6 mg/dL; 11.1-56.1; P = .003), and lower HDL (-7.6 mg/dL; -12.1 to -3.0; P =
      .001) after adjustment for race, gender, age, and ethnicity. Results remained
      significant after additional adjustment for BMI z score: TC (14.9 mg/dL; 4.9
      24.9; P = .003), LDL (16.6 mg/dL; 10.1-23.2; P < .001), TG (32.7 mg/dL; 7.7-57.7;
      P = .01), and lower HDL (-6.4 mg/dL; -12.2 to -0.7; P = .03). CONCLUSIONS:
      Children with DS have less favorable lipid profiles than their siblings
      independent of weight status. These findings may have important implications for
      the screening and treatment of this large population at increased risk for
      ischemic heart disease.

PMID- 22585769
TI  - Focal segmental glomerulosclerosis in patients with complete deletion of one WT1
      allele.
AB  - The renal prognosis of patients with Wilms' tumor, aniridia, genitourinary
      anomalies, and mental retardation syndrome (WAGR) is poor. However, the renal
      histology and its mechanisms are not well understood. We performed renal biopsies
      in 3 patients with WAGR syndrome who had heavy proteinuria. The complete deletion
      of one WT1 allele was detected in each patient by constitutional chromosomal
      deletion at 11p13 using G-banding, high-resolution G-banding, and fluorescence in
      situ hybridization. The patients exhibited proteinuria at the ages of 6, 10, and
      6 years and were diagnosed as having focal segmental glomerulosclerosis (FSGS) at
      the ages of 7, 16 and 19 years, respectively. They exhibited normal or mildly
      declined renal function at the time of biopsy. Re-examination of a nephrectomized
      kidney from 1 patient revealed that some glomeruli showed segmental sclerosis,
      although he did not have proteinuria at the time of nephrectomy. The other 2
      patients did not develop Wilms' tumor and thus did not undergo nephrectomy,
      chemotherapy, or radiotherapy, thereby eliminating any effect of these therapies
      on the renal histology. In conclusion, complete deletion of one WT1 allele may
      induce the development of FSGS. Our findings suggest that haploinsufficiency of
      the WT1 could be responsible for the development of FSGS.

PMID- 22585770
TI  - Low rates of influenza immunization in young children under Ontario's universal
      influenza immunization program.
AB  - OBJECTIVES: To determine physician-administered influenza vaccine coverage for
      children aged 6 to 23 months in a jurisdiction with a universal influenza
      immunization program during 2002-2009 and to describe predictors of vaccination.
      METHODS: By using hospital records, we identified all infants born alive in
      Ontario hospitals from April 2002 through March 2008. Immunization status was
      ascertained by linkage to physician billing data. Children were categorized as
      fully, partially, or not immunized depending on the number and timing of vaccines
      administered. Generalized linear mixed models determined the association between
      immunization status and infant, physician, and maternal characteristics. RESULTS:
      Influenza immunization was low for the first influenza season of the study period
      (1% fully immunized during the 2002-2003 season), increased for the following 3
      seasons (7% to 9%), but then declined (4% to 6% fully immunized during the 2006
      2007 to 2008-2009 seasons). Children with chronic conditions or low birth weight
      were more likely to be immunized. Maternal influenza immunization (adjusted odds
      ratio 4.31; 95% confidence interval 4.21-4.40), having a pediatrician as the
      primary care practitioner (adjusted odds ratio 1.85; 95% confidence interval 1.68
      2.04), high visit rates, and better continuity of care were all significantly
      associated with full immunization, whereas measures of social disadvantage were
      associated with nonimmunization. Low birth weight infants discharged from
      neonatal care in the winter were more likely to be immunized. CONCLUSIONS:
      Influenza vaccine coverage among children aged 6 to 23 months in Ontario is low,
      despite a universal vaccination program and high primary care visit rates.
      Interventions to improve coverage should target both physicians and families.

PMID- 22585773
TI  - Injuries associated with bottles, pacifiers, and sippy cups in the United States,
      1991-2010.
AB  - OBJECTIVE: To describe the epidemiology of injuries related to bottles,
      pacifiers, and sippy cups among young children in the United States. METHODS: A
      retrospective analysis was conducted by using data from the National Electronic
      Injury Surveillance System for children <3 years of age treated in emergency
      departments (1991-2010) for an injury associated with a bottle, pacifier, or
      sippy cup. RESULTS: An estimated 45398 (95% confidence interval: 38 770-52 026)
      children aged <3 years were treated in emergency departments for injuries related
      to these products during the study period, an average of 2270 cases per year.
      Most injuries involved bottles (65.8%), followed by pacifiers (19.9%) and sippy
      cups (14.3%). The most common mechanism was a fall while using the product (86.1%
      of injuries). Lacerations comprised the most common diagnosis (70.4%), and the
      most frequently injured body region was the mouth (71.0%). One-year-old children
      were injured most often. Children who were aged 1 or 2 years were nearly 2.99
      times (95% confidence interval: 2.07-4.33) more likely to sustain a laceration
      compared with any other diagnosis. Product malfunctions were relatively uncommon
      (4.4% of cases). CONCLUSIONS: This study is the first to use a nationally
      representative sample to examine injuries associated with these products. Given
      the number of injuries, particularly those associated with falls while using the
      product, greater efforts are needed to promote proper usage, ensure safety in
      product design, and increase awareness of American Academy of Pediatrics'
      recommendations for transitioning to a cup and discontinuing pacifier use.

PMID- 22585772
TI  - Infant outcomes after maternal antiretroviral exposure in resource-limited
      settings.
AB  - BACKGROUND AND OBJECTIVE: The impact of maternal antiretrovirals (ARVs) during
      pregnancy, labor, and postpartum on infant outcomes is unclear. METHODS: Infants
      born to HIV-infected mothers in ARV studies were followed for 18 months. RESULTS:
      Between June 2006 and December 2008, 236 infants enrolled from Africa (n = 36),
      India (n = 47), Thailand (n = 152), and Brazil (n = 1). Exposure to ARVs in
      pregnancy included >= 3 ARVs (10%), zidovudine/intrapartum ARV (81%), and
      intrapartum ARV (9%). There were 4 infant infections (1 in utero, 3 late
      postpartum) and 4 deaths with 1.8% mortality (95% confidence interval [CI], 0.1%
      3.5%) and 96.4% HIV-1-free survival (95% CI, 94.0%-98.9%). Birth weight was >=
      2.5 kg in 86%. In the first 6 months, Indian infants (nonbreastfed) had lowest
      median weights and lengths and smallest increases in growth. After 6 months,
      African infants had the lowest median weight and weight-for-age z scores. Infants
      exposed to highest maternal viral load had the lowest height and height-for-age z
      scores. Serious adverse events occurred in 38% of infants, did not differ by
      country, and correlated with less maternal ARV exposure. Clinical diagnoses were
      seen in 84% of Thai, 31% of African, and 9% of Indian infants. Congenital
      defects/inborn errors of metabolism were seen in 18 (7.6%) infants, of which 17
      were Thai (11%: 95% CI, 6.7%-17.0%); none had first trimester ARV exposure.
      CONCLUSIONS: Infant follow-up in large international cohorts is feasible and
      provides important safety and HIV transmission data following maternal ARV
      exposure. Increased surveillance increases identification of congenital/inborn
      errors.

PMID- 22585771
TI  - Incidental medical information in whole-exome sequencing.
AB  - Genomic technologies, such as whole-exome sequencing, are a powerful tool in
      genetic research. Such testing yields a great deal of incidental medical
      information, or medical information not related to the primary research target.
      We describe the management of incidental medical information derived from whole
      exome sequencing in the research context. We performed whole-exome sequencing on
      a monozygotic twin pair in which only 1 child was affected with congenital
      anomalies and applied an institutional review board-approved algorithm to
      determine what genetic information would be returned. Whole-exome sequencing
      identified 79525 genetic variants in the twins. Here, we focus on novel variants.
      After filtering artifacts and excluding known single nucleotide polymorphisms and
      variants not predicted to be pathogenic, the twins had 32 novel variants in 32
      genes that were felt to be likely to be associated with human disease. Eighteen
      of these novel variants were associated with recessive disease and 18 were
      associated with dominantly manifesting conditions (variants in some genes were
      potentially associated with both recessive and dominant conditions), but only 1
      variant ultimately met our institutional review board-approved criteria for
      return of information to the research participants.

PMID- 22585774
TI  - Oral dimenhydrinate versus placebo in children with gastroenteritis: a randomized
      controlled trial.
AB  - OBJECTIVE: To evaluate the efficacy and safety of oral dimenhydrinate in the
      treatment of acute gastroenteritis. METHODS: This was a randomized, double-blind,
      placebo-controlled trial conducted in the emergency department of a pediatric
      university-affiliated center. Children 1 to 12 years old who presented to the
      emergency department with at least 5 episodes of vomiting in the previous 12
      hours and diagnosed with acute gastroenteritis were block-randomized to receive
      oral dimenhydrinate (1 mg/kg; maximum: 50 mg) every 6 hours for 4 doses or
      placebo for 4 doses. The primary outcome measure was treatment failure as defined
      by the occurrence of >= 2 episodes of vomiting in the 24 hours after
      administration of the first dose of the study medication. RESULTS: During the
      study period, 209 patients met inclusion criteria, but 50 refused to participate
      and 7 were missed. Eight participants were lost to follow-up, and 144 were thus
      included in the primary analysis. Of these patients, 74 were randomized to
      receive dimenhydrinate and 70 placebo. The proportions of patients showing
      failure of treatment were similar for both treatment groups: dimenhydrinate, 31%
      (23 of 74); placebo, 29% (20 of 70) (difference: 0.02 [95% confidence interval: 
      0.12 to 0.17]). There were no differences between the 2 groups in rates of
      intravenous cathether insertion, mean number of episodes of vomiting or diarrhea,
      abdominal pain, nausea, duration of symptoms, revisit rates, or parental
      absenteeism. The proportions of adverse effects were similar in both groups (53%
      vs 54%). CONCLUSIONS: The prescription of oral dimenhydrinate did not
      significantly decrease the frequency of vomiting in children with acute
      gastroenteritis compared with placebo.

PMID- 22585775
TI  - Genetic and environmental influences on infant sleep.
AB  - BACKGROUND: Sleep duration is attracting increasing attention in relation to
      chronic disease risk, but few large-scale studies have investigated the
      determinants of sleep characteristics in early life. In this study we used data
      from a large, population-based twin study to examine genetic and environmental
      influences on sleep duration and sleep difficulties in infancy. METHODS:
      Participants were 1931 pairs of young twins (3862 children) from the Gemini twin
      birth cohort. Sleep patterns were assessed at 15 months by using a modification
      of the Brief Infant Sleep Questionnaire completed by parents. Outcomes included
      nighttime and daytime sleep duration and frequency of night waking. RESULTS: Twin
      analyses showed that nighttime sleep duration was predominantly influenced by the
      shared environment (66%, confidence interval [CI] 63%-70%) with a modest genetic
      effect (26%, CI 22%-30%). A similar pattern was observed for daytime nap duration
      (shared environment: 57%, CI 53%-62%; genetic effect: 37%, CI 33%-41%) and sleep
      disturbance (shared environment: 55%, 44%-64%) with a genetic effect of 40% (30%
      51%). These estimates were similar for boys and girls. CONCLUSIONS: These results
      indicate an important contribution of the shared family environment as well as
      genes to children's sleep behavior. There is a need for research to identify
      specific environmental determinants that could provide targets for interventions
      to improve sleep quality.

PMID- 22585776
TI  - Plant proteins containing high mobility group box DNA-binding domains modulate
      different nuclear processes.

PMID- 22585784
TI  - Effects of camelina meal supplementation on ruminal forage degradability,
      performance, and physiological responses of beef cattle.
AB  - Three experiments compared ruminal, physiological, and performance responses of
      beef steers consuming hay ad libitum and receiving grain-based supplements
      without (control) or with (CAM) the inclusion of camelina meal. In Exp. 1, 9
      steers fitted with ruminal cannulas received CAM (2.04 kg of DM/d; n = 5) or
      control (2.20 kg of DM/d; n = 4). Steers receiving CAM had reduced (P = 0.01)
      total DMI and tended to have reduced (P = 0.10) forage DMI compared with control.
      No treatment effects were detected (P >= 0.35) for ruminal hay degradability
      parameters. In Exp. 2, 14 steers fed CAM (1.52 kg of DM/d; n = 7) or control
      (1.65 kg of DM/d; n = 7) were assigned to a corticotropin-releasing hormone (CRH;
      0.1 MUg/kg of BW) and a thyrotropin-releasing hormone (TRH; 0.33 MUg/kg of BW)
      challenge. Steers fed CAM had greater (P < 0.05) serum concentrations of PUFA
      compared with control before challenges. Upon CRH infusion, plasma haptoglobin
      concentrations tended (P = 0.10) to be reduced and ceruloplasmin concentrations
      increased at a lesser rate in CAM steers compared with control (treatment * time;
      P < 0.01). Upon TRH infusion, no treatment effects were detected (P >= 0.55) for
      serum thyrotropin-stimulating hormone, triiodothyronine, and thyroxine. In Exp.
      3, 60 steers were allocated to 20 pens. Pens were assigned randomly to receive
      CAM (2.04 kg of DM/steer daily; n = 10) or control (2.20 kg of DM/steer daily; n
      = 10) during preconditioning (PC; d -28 to 0). On d 0, steers were transported
      for 24 h. Upon arrival, pens were assigned randomly to receive CAM or control
      during feedlot receiving (FR; d 1 to 29). During PC, CAM steers had reduced (P <
      0.01) forage and total DMI, and tended to have reduced (P = 0.10) ADG compared
      with control. Plasma linolenic acid concentrations increased during PC for CAM
      steers, but not for control (treatment * day; P = 0.02). During FR, steers fed
      CAM during PC had reduced (P < 0.01) forage and total DMI, but tended (P = 0.10)
      to have greater G:F compared with control. Steers fed CAM during FR had greater
      (P < 0.05) plasma concentrations of PUFA, and reduced rectal temperature and
      concentrations of haptoglobin and ceruloplasmin during FR compared with control.
      In summary, CAM supplementation to steers impaired forage and total DMI, did not
      alter thyroid gland function, increased circulating concentrations of PUFA, and
      lessened the acute-phase protein reaction elicited by neuroendocrine stress
      responses.

PMID- 22585785
TI  - Supplemental butyrate does not enhance the absorptive or barrier functions of the
      isolated ovine ruminal epithelia.
AB  - Our objective was to determine if increasing the ruminal butyrate concentration
      would improve the selective permeability of ruminal epithelia. Suffolk wether
      lambs (n = 18) with an initial BW of 47.4 +/-1.4 kg were housed in individual
      pens (1.5 * 1.5 m) with rubber mats on the floor. Lambs were blocked by initial
      BW into 6 blocks and, within block, were randomly assigned to either the control
      (CON) or 1 of 2 butyrate supplementation amounts (i.e., 1.25% or 2.50% butyrate
      as a proportion of DMI). With the exception of butyrate supplementation, all
      lambs were fed a common diet (90% concentrate and 10% barley silage). After a 14
      d feeding period, lambs were killed, and ruminal epithelia from the ventral sac
      were mounted in Ussing chambers. To facilitate the Ussing chamber measurements,
      only 1 lamb was killed on an individual day. Thus, the starting date was
      staggered so that all lambs were exposed to the same experimental protocol. In
      Ussing chambers, epithelia were incubated using separate mucosal (pH 6.2) and
      serosal (pH 7.4) bathing solutions. Then 1-14C-butyrate (74 kBq/10 mL) was added
      to the mucosal side and was used to measure the mucosal-to-serosal flux (J(ms
      butyrate)) in 2 consecutive 60-min flux periods with simultaneous measurement of
      transepithelial conductance (G(t)). During the first (challenge) flux period, the
      mucosal buffer solution was either acidified to pH 5.2 (ACID) or used as a
      control (pH 6.2; SHAM). Buffer solutions bathing the epithelia were replaced
      before the second flux period (recovery). Total ruminal short-chain fatty acid
      and butyrate concentrations were greater (P = 0.001) in lambs fed 2.50% compared
      with those fed 0% or 1.25% butyrate. The J(ms-butyrate) was less for lambs fed
      1.25% and 2.50% butyrate [3.00 and 3.12 MUmol/(cm2.h), respectively] than for CON
      [3.91 MUmol/(cm2. h)]. However, no difference (P = 0.13)was observed for G(t). An
      ex vivo treatment * flux period interaction was detected (P = 0.003) for J(ms
      butyrate), where no differences were present between ACID and SHAM during the
      challenge period, but the Jms-butyrate was less for ACID than for SHAM during
      recovery. These results indicate that large increases in the ruminal butyrate
      concentration decrease the selective permeability of the isolated ruminal
      epithelia.

PMID- 22585786
TI  - Effect of various doses of injected selenium on performance and physiological
      responses of sheep to heat load.
AB  - The aim of the study was to determine the effects of various doses of injected Se
      on the physiological responses of sheep to heat load. Fifteen 9-mo-old Australian
      Merino wethers (mean BW = 27.2 +/- 2.1 kg) were randomly assigned to 1 of 3
      treatments: 0 (control), 0.5, and 5 mg of Se, which was administered as a
      subcutaneous sodium selenate injection (5 mg/mL Se) on d 1, 8, and 15 of exposure
      to heat stress. The animals were housed individually in an environmental chamber
      and exposed to high temperature from 0700 to 1800 h (maximum = 38 degrees C;
      minimum = 24 degrees C) and to thermoneutral temperature from 1800 to 0700 h
      (maximum = 24 degrees C; minimum = 20 degrees C) for 21 d. Rectal temperature
      (RT) and respiration rate (RR) were measured daily at 0800, 1200, and 1600 h.
      Feed intake was measured daily, and sheep were weighed on d 1, 8, 15, and 21.
      Blood samples were collected on d 1 and 21. The 5 mg Se treatment decreased RT by
      0.3 degrees C (P = 0.02) and BW loss by 4.5% (P < 0.05) and increased eosinophil
      count (P < 0.05). There were no differences (P > 0.05) between treatments in RR
      and DMI, serum concentrations of glucose, total protein, cholesterol, and NEFA or
      in blood hematology variables. The findings of this study have important
      implications for the sheep industry. Further studies are warranted to elucidate
      the dynamics of Se on productivity and health during hot conditions.

PMID- 22585787
TI  - Effects of dietary spray-dried egg on growth performance and health of weaned
      pigs.
AB  - Four experiments were conducted to evaluate the nutrient contributions and
      physiological health benefits of spray-dried egg (SDE) containing only
      unfertilized eggs as a protein source in nursery pig diets. In all experiments,
      all diets were formulated to the same ME and Lys content, and each pen within a
      block (by BW) housed the same number of barrows and gilts. In Exp. 1 and 2 (168
      and 140 pigs, respectively; 5 kg BW; 16 d old; 14 replicates/experiment),
      conducted at a university farm, treatments were with or without 5% SDE in a
      nursery control diet, which included antibiotics and zinc oxide. Pigs were fed
      for 10 d after weaning to measure ADG, ADFI, and G:F. The SDE increased (P <
      0.05) ADG (Exp. 1: 243 vs. 204 g/d; Exp. 2: 204 vs. 181 g/d) and ADFI (Exp. 1:
      236 vs. 204 g/d; Exp. 2: 263 vs. 253 g/d) compared with the control diet but did
      not affect G:F. In Exp. 3 (1,008 pigs; 5.2 kg BW; 20 d old; 12
      replicates/treatment), conducted at a commercial farm, treatments were in a
      factorial arrangement of with or without SDE and high or low spray-dried plasma
      (SDP) in nursery diets, which included antibiotics and zinc oxide. Pigs were fed
      for 6 wk using a 4-phase feeding program (phases of 1, 1, 2, and 2 wk,
      respectively) with declining diet complexity to measure ADG, ADFI, G:F, removal
      rate (mortality plus morbidity), and frequency of medical treatments per pen and
      day (MED). The diets with the SDE increased (P < 0.05) ADFI during phase 1 only
      (180 vs. 164 g/d) compared with the diets without the SDE but did not affect
      growth performance during any other phases. The diets with SDE reduced MED during
      phase 1 (0.75% vs. 1.35%; P < 0.05) and the overall period (0.84% vs. 1.01%; P =
      0.062) compared with the diets without the SDE but did not affect removal rate.
      In Exp. 4 (160 pigs; 6.7 kg BW; 21 d old; 10 replicates/treatment), conducted at
      a university farm to determine whether SDE can replace SDP, treatments were in a
      factorial arrangement of with or without SDP or SDE in nursery diets, which
      excluded antibiotics and zinc oxide. Pigs were fed for 6 wk using the same
      schedule used in Exp. 3 to measure ADG, ADFI, and G:F. The diets with SDE
      increased (P < 0.05) ADFI during phase 1 only (195 vs. 161 g/d) compared with the
      diets without SDE but did not affect growth performance during any other periods.
      In conclusion, SDE can be an efficacious protein and energy source in nursery pig
      diets and improves health and, in some instances, increases growth rate.

PMID- 22585788
TI  - Effects of temperament and acclimation to handling on reproductive performance of
      Bos taurus beef females.
AB  - Two experiments evaluated the effects of temperament and acclimation to handling
      on reproductive performance of Bos taurus beef females. In Exp. 1, 433
      multiparous, lactating Angus * Hereford cows were sampled for blood and evaluated
      for temperament before the breeding season. Cow temperament was assessed by chute
      score and exit velocity. Chute score was assessed on a 5-point scale according to
      behavioral responses during chute restraining. Exit score was calculated by
      dividing exit velocity into quintiles and assigning cows with a score from 1 to 5
      (1 = slowest, 5 = fastest cows). Temperament score was calculated by averaging
      chute and exit scores. Cows were classified for temperament type according to
      temperament score (<= 3 = adequate, > 3 = aggressive). Plasma cortisol
      concentrations were greater (P < 0.01) in cows with aggressive vs. adequate
      temperament. Cows with aggressive temperament had reduced (P <= 0.05) pregnancy
      and calving rate and tended to have reduced (P = 0.09) weaning rate compared with
      cows with adequate temperament. Hence, kilogram of calf born per cow was reduced
      (P = 0.05) and kilogram of calf weaned per cow tended to be reduced (P = 0.08) in
      aggressive cows. In Exp. 2, 88 Angus * Hereford heifers (initial age = 206 +/- 2
      d) were weighed (d 0 and 10) and evaluated for temperament score (d 10). On d 11,
      heifers were ranked by these variables and assigned to receive or not (control)
      an acclimation treatment. Acclimated heifers were processed through a handling
      facility 3 times weekly for 4 wk (d 11 to 39; Mondays, Wednesdays, and Fridays),
      whereas control heifers remained undisturbed on pasture. Heifer puberty status,
      evaluated via plasma progesterone concentrations, was assessed on d 0 and 10, d
      40 and 50, 70 and 80, 100 and 110, 130 and 140, 160 and 170, and 190 and 200.
      Blood samples collected on d 10 and 40 were also analyzed for plasma
      concentrations of cortisol and haptoglobin. Temperament score was assessed again
      on d 40 and d 200. Acclimated heifers had reduced (P = 0.01) concentrations of
      cortisol and haptoglobin on d 40 and reduced (P = 0.02) exit velocity on d 200
      compared with control heifers. Puberty was hastened in acclimated heifers
      compared with control (P = 0.01). Results from this study indicate that B. taurus
      beef cows with aggressive temperament have impaired reproductive performance
      compared with cohorts with adequate temperament, whereas acclimation to human
      handling after weaning hastens reproductive development of replacement heifers.

PMID- 22585789
TI  - Effect of beta-mannanase on the digestibility of diets with different protein
      sources in dogs determined by different methodologies.
AB  - This experiment aimed at evaluating the effects of including the enzyme, beta
      mannanase, in dog (Canis lupus familiaris) diets based on either poultry (Gallus
      gallus domesticus) by-product meal (PBM) or soybean [Glycine max (L.) Merr.] Meal
      (SBM). The second objective was to evaluate 3 methods for determining energy and
      nutrient digestibility values in diets fed to dogs: total fecal collection (TFC)
      and use of aia or crude fiber (CF) as a marker. Eight dogs were allotted to a
      replicated latin square (4 by 4) design. There were 2 diets based on PBM as the
      major protein source and 2 diets based on SBM as the major protein source. Within
      each protein source, 1 diet contained no beta-mannanase and 1 diet contained
      0.01% beta-mannanase. Diets were fed for an adaptation period of 5 d followed by
      5 d of TFC. Fecal score (1 = watery feces to 5 = dry, hard pellets), pH, DM, and
      fecal volume were determined. The apparent total tract digestibility (ATTD) of
      DM, OM, CP, ether extract (EE), N-free extract (NFE), and GE, and ME content were
      calculated using the methods of TFC, AIA, and CF. Data were analyzed as a 2 by 2
      by 3 split-split-plot design (beta-mannanase, protein source, and digestibility
      calculation procedure). There were interactions between protein source and beta
      mannanase (P < 0.05). Supplementation of beta-mannanase increased ATTD of
      nutrients and energy and ME (+ 195.3 kcal/kg) and also reduced fecal production
      in the diet with SBM, but not in the diet that contained PBM. There was an
      interaction between digestibility calculation procedure and protein source (P <
      0.05). The use of AIA overestimated ATTD of the diets containing PBM, but
      digestibility values estimated based on TFC and CF were not different. Dogs fed
      diets containing SBM produced more feces with greater moisture content and lower
      pH compared with dogs fed the PBM diet (P < 0.05). Addition of 0.01% beta
      mannanase increased (P < 0.05) the digestibility and ME content of the diets
      containing SBM, but did not improve (P > 0.05) fecal texture. Results indicated
      that values for ATTD of energy and nutrients in diets containing sbm are not
      different if they are calculated based on TFC, AIA, or CF, but use of AIA may
      result in an overestimation of values for ATTD of energy and nutrients in diets
      containing PBM.

PMID- 22585790
TI  - Effects of corn processing method and dietary inclusion of wet distillers grains
      with solubles on energy metabolism, carbon-nitrogen balance, and methane
      emissions of cattle.
AB  - The growing ethanol industry in the Southern Great Plains has increased the use
      of wet distillers grains with solubles (WDGS) in beef cattle (Bos taurus)
      finishing diets. Few studies have used steam-flaked corn (Zea mays L.; SFC)-based
      diets to evaluate the effects of WDGS in finishing cattle diets, and a reliable
      estimate of the net energy value of WDGS has yet to be determined. Effects of
      corn processing method and WDGS on energy metabolism, C and N balance, and
      enteric methane (CH(4)) production were evaluated in a short-term study using 8
      Jersey steers and respiration calorimetry chambers. A 2 by 2 factorial
      arrangement of treatments was used in a Latin square design. The 4 treatment
      combinations consisted of: i) SFC-based diet with 0% WDGS (SFC-0); ii) SFC-based
      diet with 30% WDGS (SFC-30); iii) dry-rolled corn (DRC)-based diet with 0% WDGS
      (DRC-0); and iv) DRC-based diet with 30% WDGS (DRC-30). Diets were balanced for
      degradable intake protein (DIP) and ether extract (EE) by the addition of
      cottonseed (Gossypium hirsutum L.) meal and yellow grease. As a proportion of GE,
      grain processing method did not affect (P >= 0.12) fecal, digestible, urinary,
      and ME, or heat production. Steers consuming SFC-based diets produced less (P <
      0.04) CH(4) than steers consuming DRC-based diets. Retained energy tended to be
      greater (P = 0.09) for cattle consuming SFC- than DRC-based diets. Inclusion of
      WDGS did not affect (P >= 0.17) fecal, digestible, urinary, metabolizable, and
      retained energy, or heat production as a proportion of GE. Furthermore, neither
      inclusion of WDGS or grain processing method affected (P >= 0.17) daily CO(2)
      production. Due in part to greater N intake, cattle consuming diets containing
      30% WDGS excreted more (P = 0.01) total N and excreted a greater (P < 0.01)
      quantity of N in the urine. From these results, we conclude that cattle consuming
      SFC-based diets produce less CH(4) and retain more energy than cattle fed DRC
      based diets; however, dietary inclusion of WDGS at 30% seems to have little
      effect on CH(4) production and energy metabolism when diets are balanced for DIP
      and EE. Cattle excrete a greater amount of C when fed DRC compared with SFC-based
      diets, and dietary inclusion of 30% WDGS increases urinary N excretion. Finally,
      we determined the NE(g) values for WDGS were 1.66 and 1.65 Mcal/kg in a SFC or
      DRC-based diet, respectively, when WDGS replaced 30% of our control (SFC-0 and
      DRC-0) diets.

PMID- 22585791
TI  - Genome-wide association study of swine farrowing traits. Part I: genetic and
      genomic parameter estimates.
AB  - The primary objective of this study was to determine genetic and genomic
      parameters among swine (Sus scrofa) farrowing traits. Genetic parameters were
      obtained using MTDFREML. Genomic parameters were obtained using GENSEL. Genetic
      and residual variances obtained from MTDFREML were used as priors for the Bayes C
      analysis of GENSEL. Farrowing traits included total number born (TNB), number
      born alive (NBA), number born dead (NBD), number stillborn (NSB), number of
      mummies (MUM), litter birth weight (LBW), and average piglet birth weight (ABW).
      Statistically significant heritabilities included TNB (0.09, P = 0.048), NBA
      (0.09, P = 0.041), LBW (0.20, P = 0.002), and ABW (0.26, P < 0.0001).
      Statistically significant genetic correlations included TNB-NBA (0.97, P <
      0.0001), TNB-LBW (0.74, P < 0.0001), NBA-LBW (0.56, P < 0.0017), NSB-LBW (0.87, P
      < 0.0395), and LBW-ABW (0.63, P < 0.0002). Genetic parameters are similar to
      others found in the literature. The proportion of phenotypic variance explained
      by genomic markers (GP) generated by GENSEL was TNB (0.04), NBA (0.06), NBD
      (0.00), NSB (0.01), MUM (0.00), LBW (0.11), and ABW (0.31). Limited information
      is available in the literature about genomic parameters. Only the GP estimate for
      NSB is significantly lower than what has been published. The GP estimate for ABW
      is greater than the estimate for heritability found in this study. Other traits
      with significant heritability had GP estimates half the value of heritability.
      This research indicates that significant genetic markers will be found for TNB,
      NBA, LBW, and ABW that will have either immediate use in industry or provide a
      roadmap to further research with fine mapping or sequencing of areas of
      significance. Furthermore, these results indicate that genomic selection
      implemented at an early age would have similar annual progress as traditional
      selection, and could be incorporated along with traditional selection procedures
      to improve genetic progress of litter traits.

PMID- 22585792
TI  - Pre-orbital gland opening: part of sucking behavior in red deer (Cervus elaphus)
      calves.
AB  - Opening of the pre-orbital gland in red deer (Cervus elaphus) was previously
      found to be associated with feeding and negatively associated with achieving
      satiety in bottle-reared red deer calves. We speculated that this acted as a
      signal from a calf to the mother that it was hungry. Thus, we focused on a
      possible association between the pre-orbital gland opening and the sucking
      behavior in red deer calves. We recorded 63 sucking attempts and 150 sucking
      bouts within a stable social group of 24 farmed red deer females with 19 calves
      ages 16 to 90 d. The probability of the pre-orbital gland opening or remaining
      open during a sucking bout rapidly decreased with the on-going sucking phase (P <
      0.001), and it was less after than during a sucking attempt (P < 0.03). The
      proportion of open pre-orbital glands at the end of sucking depended on whether
      the nursing female (27.85%) or the calf (0%, P < 0.01) terminated the sucking
      bout. The open pre-orbital gland of the calf after the sucking bout significantly
      predicted a subsequent sucking attempt (P < 0.001). The probability of open pre
      orbital gland was not significantly affected by the age of the calf, sex or birth
      weight, or age of the nursing female. In conclusion, our study provides evidence
      that the opening of the pre-orbital gland is one of the general patterns of calf
      sucking behavior, specifically that it reflects the level of satisfying calf
      needs.

PMID- 22585793
TI  - Cage size and enrichment effects on the bone quality and fluctuating asymmetry of
      fattening rabbits.
AB  - We studied the effect of increased cage size on different aspects of bone quality
      (bone strength, diameter, weight, and length) and fluctuating asymmetry (FA).
      Such characteristics may indicate improved animal welfare, as greater bone
      quality may decrease fracture incidence during handling, whereas decreased FA has
      been suggested to signal decreased stress. As stress is likely not only
      influenced by the quantity of space, but also by its quality, we also studied the
      effect of environmental enrichment. Groups of 8 rabbits were housed in wire open
      top cages of 0.40, 0.46, 0.53, 0.64, 0.80, 1.07, and 1.60 m(2) from weaning until
      slaughter. All cages of 0.40 and 0.46 m(2) (12 cages/size) were left barren to
      allow sufficient mobility. One-half of the larger cages were enriched with a
      wooden-enrichment structure that could be used to gnaw on, hide in, or lie in (6
      cages per size * enrichment treatment). Increased cage size led to an increase in
      tibiofibula diameter (P = 0.008), a tendency for increased tibiofibula weight (P
      = 0.051), and decreased FA (P = 0.010), suggesting improved welfare. Bone length
      and strength were not affected by cage size (P > 0.1). Enrichment did not affect
      FA (P > 0.1), in contrast with our expectations based on previous glucocorticoid
      analysis. This discrepancy between indicators may be due to sensitivity to other
      types of stressors or different sensitive periods. In summary, rabbits housed in
      larger cages had wider, heavier bones, but the absence of changes in bone
      strength indicate that this is unlikely to result in decreased fracture
      incidence. In larger cages, FA was lower, suggesting a favorable effect on
      welfare, whereas no effect of enrichment was shown.

PMID- 22585794
TI  - Effects of the provision of large amounts of solid feeds to veal calves on growth
      and slaughter performance and intravitam and postmortem welfare indicators.
AB  - Polish Friesian male calves (n = 78) were used to investigate the effects of
      innovative feeding plans based on the provision of large amounts of solid feeds
      on growth performance, welfare, and carcass characteristics of veal calves.
      Groups of calves (initial BW 71.5 +/- 3.7 kg) were fed 1 of 3 treatments (26
      calves/treatment): 1) milk replacer plus corn grain (CG), 2) milk replacer plus
      an 80:20 mixture (as-fed basis) of corn grain and wheat straw (CGS), or 3) milk
      replacer plus a 72:20:8 mixture (as-fed basis) of corn grain, wheat straw, and
      extruded soybean, respectively (CGSES). All the treatments provided at least 170
      kg DM/calf from solid feed throughout the 206 d of fattening. Type and
      concentration of milk replacer were the same for all calves throughout fattening.
      Calves fed CGSES received 96% of the daily amount of milk replacer delivered to
      CG and CGS to balance the dietary CP content. No differences (P >= 0.063) among
      treatments were observed for growth performance and DMI. Health status of CG
      calves was less than CGSES calves, as indicated by the greatest (P < 0.001)
      proportion of milk replacer refusal events and the greatest (P < 0.001) incidence
      of treatments for respiratory disorders. Inclusion of straw and soybean in the
      solid feeds increased (P < 0.001) the daily intake of iron in CGS and CGSES as
      compared with CG; however, blood hemoglobin concentrations measured at d 5 and 31
      were greater (P < 0.05) than when measured on d 80, 122, and 206 of fattening.
      Feeding treatment did not (P >= 0.107) affect HCW, dressing percentage, or
      carcass color. Calves fed CG had heavier (P < 0.001) reticulorumens and more (P <
      0.001) developed rumens than CGS and CGSES calves, but 84% and 68% of CG rumens
      (P < 0.001) showed overt signs of hyperkeratinization and plaques, respectively.
      These alterations of rumen mucosa were not detected in CGSES calves, and only 8%
      of CGS calves had rumen plaques. Regardless of feeding treatment, postmortem
      inspection recorded a prevalence of more than 84% abomasal lesions. When feeding
      veal calves with large amounts of solids, it is advisable to avoid the provision
      of corn grain alone and replace part of the cereal with a roughage source to
      improve calf health and prevent rumen mucosa alterations.

PMID- 22585795
TI  - Urinary excretion of purine derivatives, microbial protein synthesis, nitrogen
      use, and ruminal fermentation in sheep and goats fed diets of different quality.
AB  - The objective of this study was to compare N balance, microbial N flow (MNF)
      estimated from purine derivatives (PD) urinary excretion, and its variation when
      estimated using purine bases:N ratios in liquid associated bacteria (LAB) from
      models reported in the literature (MNF - response models) or measured ratios in
      liquid and solid-associated bacterial (SAB) pellets (MNF-LAB+SAB), diet
      digestibility, and rumen fermentation variables in sheep and goats fed 3
      different practical, quality diets to study interspecies differences concerning N
      use as accurately as possible. Four mature female Merino sheep and 4 mature
      female Granadina goats, each fitted with a ruminal cannula, were used in 3 * 3
      Latin square design with an extra animal. Two experimental diets had a forage-to
      concentrate ratio of 70:30 (DM basis) with alfalfa hay (ALC) or grass hay (GRC)
      as forage, and the third diet contained 70% concentrate and 30% alfalfa hay
      (CAL). All animals were fed the diets at a daily rate of 56 g/kg BW(0.75) to
      minimize feed selection. Digestibility of nutrients was similar (P = 0.16 to
      0.88) in the 2 species, but some animal species * diet interactions (P = 0.01 to
      0.04) were detected. There were small differences between the fermentation
      patterns of both animal species. Goats showed decreased VFA concentrations (P =
      0.005) and butyrate proportions (P = 0.04), and greater acetate proportions (P =
      0.02) compared with sheep, whereas N intake and percentage of N intake excreted
      in feces were similar in both species (P = 0.58 and 0.15, respectively), the
      percentage excreted via the urine was greater in goats compared with sheep (P <
      0.001). As a consequence, sheep had greater (P < 0.001) N retention than goats
      (averaged across diets, 32.6% and 16.1% of N intake, respectively). There were no
      differences (P = 0.95) between animal species in total PD excretion, but goats
      showed a greater excretion of allantoin (P = 0.01) and decreased excretion of
      xanthine (P = 0.008) and hypoxanthine (P = 0.007) compared with sheep. In
      general, differences between sheep and goats were more pronounced for the medium
      quality diet (GRC) compared with those of high-quality diet (ALC and CAL). The
      greater urinary losses in goats would indicate a greater contribution of goats to
      N environmental contamination compared with sheep.

PMID- 22585796
TI  - Adaptive immune response, survival, and somatic cell score between postpartum
      Holstein and Norwegian Red * Holstein first-calf heifers.
AB  - The objectives of this study were to evaluate antibody (AMIR) and cell-mediated
      immune responses (CMIR), survival, and somatic cell score (SCS) between purebred
      Holstein (HO) and crossbred Norwegian Red * Holstein (NRHO) first-calf heifers
      postpartum. Additionally, immune response traits observed as calves in a previous
      study were correlated with their immune response traits as first-calf heifers.
      Heifers, previously immunized as calves, were bled and reimmunized 6 to 9 d
      postcalving with known type 1 and type 2 antigens and human serum albumin (HSA).
      Seven days later, heifers were rebled, and background skinfold measurements of
      the tail fold were taken. Intradermal injections of PBS and type 1 antigen were
      administered on either side of the tail fold. On d 9 final skinfold measurements
      were taken and used to assess delayed-type hypersensitivity (DTH) as an indicator
      of CMIR. Blood samples were also collected for a final time on d 14 from heifers
      that received the antigen HSA. Serum was obtained from blood collected on d 0, 7,
      and 14 and analyzed by ELISA to assess AMIR. Data on survival and somatic cell
      count, which was converted to SCS, were obtained from CanWest Dairy Herd
      Improvement (DHI). All SCS, survival, and immune response data were analyzed
      using general linear models to determine significance between HO and NRHO first
      calf heifers. To determine residual correlations between immune response traits
      observed in calves to their responses as first-calf heifers, residuals were
      obtained from models, and correlations between traits were determined using PROC
      CORR in SAS. Results showed NRHO had a greater primary IgG antibody response to
      HSA and greater tertiary IgG antibody response to the type 2 antigen compared
      with HO. Crossbreds (NRHO)also had significantly greater DTH response (P < 0.05)
      and, in general, greater survival from calving to 100 d in milk (dim), 100 to 305
      dim, calving to 305 dim, and age at immune response testing as calf to 305 dim.
      No difference was observed between breeds for SCS. Results also showed most
      correlations between calf and first-calf heifer immune response traits were found
      to be positive and significant (P < 0.05). In conclusion, NRHO heifers have
      greater survival, which likely relates at least in part to increases in aspects
      of both AMIR and CMIR and could indicate that crossbred heifers have enhanced
      disease resistance.

PMID- 22585797
TI  - Effects of exogenous enzyme supplementation to corn- and soybean meal-based or
      complex diets on growth performance, nutrient digestibility, and blood
      metabolites in growing pigs.
AB  - Two experiments were conducted to determine the effects of dietary
      supplementation of exogenous enzymes on growth performance, apparent total tract
      digestibility (ATTD) of energy and nutrients, blood metabolites, fecal VFA, and
      fecal ammonia-N in growing pigs (Sus scrofa) fed a corn (Zea mays L.)- and
      soybean [Glycine max (L.) Merr.] meal (SBM)-based diet. In Exp. 1, 240 growing
      barrows (initial BW: 55.6 +/- 0.9 kg) were randomly allotted to 5 treatments on
      the basis of BW. There were 4 replicates in each treatment with 12 pigs per
      replicate. The 5 treatments consisted of a corn-SBM-based control diet and 4
      additional diets were similar to the control diet, with the exception that 0.05%
      beta-mannanase (M), alpha-amylase + beta-mannanase (AM), beta-mannanase +
      protease (MPr), or alpha-amylase + beta-mannanase + protease (AMP) was added to
      the diets, which were fed for 28 d. Pigs fed the AM, MPr, or AMP diet had greater
      (P < 0.05) ADG than pigs fed the control diet. Pigs fed the AMP diet also had
      greater (P < 0.05) ADG than pigs fed the M, AM, or MPr diet. Pigs fed the AMP
      diet had greater (P < 0.05) G:F than pigs fed the control diet. The G:F of the
      pigs fed the M, AM, or MPr diet were not different (P > 0.05) from the G:F in
      pigs fed the AMP or control diet. The ADFI, ATTD of nutrients, blood metabolites,
      and fecal VFA and ammonia-N concentrations were not different among treatments.
      In Exp. 2, 192 growing barrows (initial BW: 56.9 +/- 1.0 kg) were allotted to 4
      treatments. There were 4 replicates in each treatment with 12 pigs per replicate.
      Pigs were fed a corn-SBM-based diet (CSD) or a complex diet (CD) that contained
      corn, SBM, 3% rapeseed (Brassica napus L.) meal, 3% copra (Cocos nucifera L.)
      meal, and 3% palm (Elaeis guineensis Jacq.) kernel meal. Each diet was prepared
      without exogenous enzymes or with 0.05% AMP and all diets were fed for 28 d. The
      ADG and G:F of pigs fed the CSD were greater (P < 0.05) than pigs fed the CD.
      However, the type of diet had no effect on the ATTD of nutrients, blood
      metabolites, or fecal VFA and ammonia-N, and there was no diet * enzyme
      interaction for any of the measured variables. Supplementation of diets with
      exogenous enzymes resulted in greater (P < 0.05) ADG, G:F, ATTD of DM, GE, and
      CP, and blood urea nitrogen (BUN) concentration. These results indicate that
      supplementation of 0.05% of AMP enzymes to a corn-SBM diet or a complex diet may
      improve the performance of growing pigs.

PMID- 22585799
TI  - Pre-orbital gland opening in farmed red deer (Cervus elaphus) during stressful
      handling.
AB  - Stressful manipulation by humans has been previously shown to result in opening
      the pre-orbital gland of the newborn red deer. We hypothesized that exposure of
      red deer to stressful handling would result in opening the pre-orbital gland.
      Further, we tested the potential factors associated with pre-orbital opening,
      including season, sex, age and struggling behavior. Pre-orbital gland status was
      observed in 76 red deer (48 males, 28 females) during 281 handling events with
      the animal isolated and fixed in a mechanical restraint cradle (crush) within 3
      consecutive years. The deer age ranged from 1 to 5 yr in males, and from 1 to 11
      yr in females at the beginning of observations. The proportion of handling events
      with an open gland was considerably greater during than before handling (27.76
      vs. 0%, respectively, P < 0.001). The deer that struggled or stiffened revealed 2
      fold greater incidence of pre-orbital opening (P < 0.01), regardless of sex.
      Thus, pre-orbital opening seemed to accompany the behaviors that have been found
      to be related to acute stress. The probability that the animal opens its pre
      orbitals during handling sharply increased at the beginning of the rut (mating
      season, P < 0.01). Deer that threatened the handler (10% out of 215 observations)
      opened their pre-orbitals 30 times more often than nonthreatening ones. These
      effects indicate that other motivations are likely involved in the opening of pre
      orbitals, in addition to the perception of a stressful event. Incidence of pre
      orbital opening decreased with age in both sexes (P < 0.05) across 3 consecutive
      yr of observations, which suggests habituation to repeated handling. Sex of the
      animal did not influence the probability of pre-orbital opening. We found
      significant variability in pre-orbital opening across the individuals (P <
      0.001). In conclusion, we confirmed an association between opening of the pre
      orbital gland and stressful handling in sub-adult and adult red deer, although
      repeated human handling did not elicit such incidence of pre-orbital opening as
      found in newborn red deer calves. Our results support multifactorial origins of
      pre-orbital opening and prompt the necessity of further research to distinguish
      between different motivations that might have been involved in opening of pre
      orbitals.

PMID- 22585800
TI  - Genome-wide association study of swine farrowing traits. Part II: Bayesian
      analysis of marker data.
AB  - Reproductive efficiency has a great impact on the economic success of pork (sus
      scrofa) production. Number born alive (NBA) and average piglet birth weight (ABW)
      contribute greatly to reproductive efficiency. To better understand the
      underlying genetics of birth traits, a genome-wide association study (GWAS) was
      undertaken. Samples of DNA were collected and tested using the Illumina
      PorcineSNP60 BeadChip from 1,152 first parity gilts. Traits included total number
      born (TNB), NBA, number born dead (NBD), number stillborn (NSB), number of
      mummies (MUM), total litter birth weight (LBW), and ABW. A total of 41,151 SNP
      were tested using a Bayesian approach. Beginning with the first 5 SNP on SSC1 and
      ending with the last 5 SNP on the SSCX, SNP were assigned to groups of 5
      consecutive SNP by chromosome-position order and analyzed again using a Bayesian
      approach. From that analysis, 5-SNP groups were selected having no overlap with
      another 5-SNP groups and no overlap across chromosomes. These selected 5-SNP non
      overlapping groups were defined as QTL. Of the available 8,814 QTL, 124 were
      found to be statistically significant (P < 0.01). Multiple testing was considered
      using the probability of false positives. Eleven QTL were found for TNB, 3 on
      SSC1, 3 on SSC4, 1 on SSC13, 1 on SSC14, 2 on SSC15, and 1 on SSC17. Statistical
      testing for NBA identified 14 QTL, 4 on SSC1, 1 on SSC4, 1 on SSC6, 1 on SSC10,
      1on SSC13, 3 on SSC15, and 3 on SSC17. A single NBD QTL was found on SSC11. No
      QTL were identified for NSB or MUM. Thirty-three QTL were found for LBW, 3 on
      SSC1, 1 on SSC2, 1 on SSC3, 5 on SSC4, 2 on SSC5, 5 on SSC6, 3 on SSC7, 2 on
      SSC9, 1 on SSC10, 2 on SSC14, 6 on SSC15, and 2 on SSC17. A total of 65 QTL were
      found for ABW, 9 on SSC1, 3 on SSC2, 9 on SSC5, 5 on SSC6, 1 on SSC7, 2 on SSC8,
      2 on SSC9, 3 on SSC10, 1 on SSC11, 3 on SSC12, 2 on SSC13, 8 on SSC14, 8 on
      SSC15, 1 on SSC17, and 8 on SSC18. Several candidate genes have been identified
      that overlap QTL locations among TNB, NBA, NBD, and ABW. These QTL when combined
      with information on genes found in the same regions should provide useful
      information that could be used for marker assisted selection, marker assisted
      management, or genomic selection applications in commercial pig populations.

PMID- 22585801
TI  - Influence of diet, phytase, and incubation time on calcium and phosphorus
      solubility in the gastric and small intestinal phase of an in vitro digestion
      assay.
AB  - To determine the influence of incubation time, diet, and particle size on Ca and
      P solubility in vitro, experimental diets were formulated to contain 0.89% Ca and
      0.40% available P (positive control; PC) or 0.76% Ca and 0.27% available P
      (negative control; NC). The PC was supplemented with 0 or 1,000 phytase units
      (FTU) of microbial phytase/kg and the NC with 0, 1,000, or 5,000 FTU/kg diet of
      microbial phytase for a total of 5 experimental diets. In Exp. 1, diets were
      exposed to simulated gastric digestion containing HCl and pepsin for 42 min, or a
      small intestinal digestion phase containing NaHCO(3) and pancreatin for 60 min.
      In Exp. 2, diets were ground to pass a 1- or 2-mm screen and exposed to gastric
      digestion for 5, 10, or 20 min. Phosphorus and Ca solubility were similarly
      influenced by diet and digestion phase (Exp. 1), and there was no interaction.
      Phytase supplementation improved (P < 0.001) Ca and P solubility in both the PC
      and NC diets (Exp. 1) and increased P (P < 0.001) and Ca (P < 0.001) solubility
      in the gastric phase of the in vitro digestion model (Exp. 2). Phytase continued
      to release P in the gastric test over time, which resulted in a diet * time
      interaction (P < 0.05). Calcium solubility reached an asymptote at 5 min and both
      Ca and P solubility was reduced (P < 0.05) in diets ground to pass a 2 mm screen
      compared with diets ground to pass a 1-mm screen. In addition, P and Ca
      solubility did not change over time in diets not supplemented with phytase. In
      conclusion, phytase or particle size altered the kinetics of Ca and P release in
      a non-parallel fashion, which may be associated with the precipitation of Ca with
      phytate and the sequential dephosphorylation of phytate by a microbial 6-phytase.
      In the presence of phytase, considerable Ca and P hydrolysis occurred within 5
      min of a simulated gastric digestion. However, the solubility of Ca and P reached
      a plateau in the gastric phase of digestion and no further improvements in
      solubility are apparent in the small intestine. Therefore, absorption of Ca and P
      may be complicated by conditions within the gastrointestinal tract, particle
      size, precipitation with anti-nutrients, and differential rates of delivery to
      the small intestine.

PMID- 22585803
TI  - Alleviation of reproductive toxicity of gossypol using selenium supplementation
      in rams.
AB  - The objective of this study was to evaluate the reproductive toxicity of gossypol
      and the possible counteracting effect of selenium supplementation in rams. Twenty
      five mature crossbred (Barki * Rahamni) rams were randomly divided into 5 equal
      groups. The first group served as a control (no gossypol in diet). The second and
      third groups received diets containing free gossypol of 9 and 14 mg.kg(-1) BW.d(
      1)(low level and high level of gossypol), respectively. The fourth and fifth
      groups received the same diets given to the second and third groups,
      respectively, with an oral administration of 1 mg selenium (as sodium selenite)
      daily for each animal. Results showed reductions in ejaculate volume (P = 0.028),
      percentage of dead sperm (P = 0.003), total functional sperm fraction (P <
      0.001), and blood serum concentration of testosterone (P < 0.001) in the presence
      of both levels of gossypol inclusion. Furthermore, high level of gossypol reduced
      forward motility (P < 0.001) and semen initial fructose concentration (P = 0.002)
      and increased abnormal-head sperm (P = 0.003) and blood serum concentration of
      triiodothyronine (P = 0.006). Regardless of selenium supplementation, increasing
      level of free gossypol in diet resulted in a significant decrease in the
      percentage of forward motility (P = 0.037) and significant increases in the mean
      values of sperm concentration (P < 0.001), total sperm output (P = 0.002),
      percentage of total abnormal sperm (P = 0.058), and abnormal-head sperm (P =
      0.016). On the other hand, regardless of levels of gossypol inclusion, selenium
      supplementation resulted in significant increases in libido (P < 0.001), mean
      values of ejaculate volume (P < 0.001), percentage of forward motility (P =
      0.019), total sperm output (P < 0.001), total functional sperm fraction (P <
      0.001), semen initial fructose concentration (P = 0.031), and blood serum
      concentrations of both testosterone and triiodothyronine (P < 0.001). In
      conclusion, free gossypol in diet induced adverse effects on semen quality in
      rams, but selenium supplementation successfully counteracts most of the hazardous
      effects of gossypol on semen characteristics.

PMID- 22585802
TI  - Amount and source of dietary copper affects small intestine morphology, duodenal
      lipid peroxidation, hepatic oxidative stress,and mRNA expression of hepatic
      copper regulatory proteins in weanling pigs.
AB  - Thirty weanling, crossbred barrows (SUS SCROFA) were used to determine the
      effects of amount and source of dietary Cu on small intestinal morphology and
      lipid peroxidation, Cu metabolism, and mRNA expression of proteins involved in
      hepatic Cu homeostasis. At 21 d of age, pigs were stratified by BW (6.33 +/- 0.23
      kg) and allocated to 1 of the following dietary treatments: i) control (no
      supplemental Cu; 6.7 mg Cu/kg), ii) 225 mg supplemental Cu/kg diet from Cu
      sulfate (CuSO(4)), or iii) 225 mg supplemental Cu/kg diet from tribasic Cu
      chloride (TBCC). Pigs were housed 2 pigs per pen and were fed a 3-phase diet
      regimen until d 35 or 36 of the study. During harvest, bile and liver were
      obtained for mineral analysis, and liver samples were also obtained for analysis
      of liver glutathione (GSH) and mRNA expression of Cu regulatory proteins.
      Segments of duodenum, proximal jejunum, and ileum were obtained for mucosal
      morphology, and duodenal mucosal scrapings were collected from all pigs for
      analysis of malondialdehyde (MDA). Duodenal villus height was reduced in CuSO(4)
      pigs compared with control (P = 0.001) and TBCC (P = 0.03) pigs. Villus height in
      the proximal jejunum of CuSO(4) pigs was reduced (P = 0.03) compared with control
      pigs, but ileal villus height was not affected (P = 0.82) by treatment. Duodenal
      MDA concentrations were greater (P = 0.03) in CuSO(4) pigs and tended to be
      greater (P = 0.10) in pigs supplemented with TBCC compared with control pigs.
      Liver Cu was greater (P = 0.01) in CuSO(4) vs. control pigs, and tended (P =
      0.07) to be greater in TBCC pigs than control pigs. Bile Cu concentrations were
      greater (P < 0.001) in CuSO(4) and TBCC pigs vs. controls and were also greater
      (P = 0.04) in TBCC vs. CuSO(4) pigs. Total liver GSH concentrations were less (P
      = 0.02) in pigs fed diets supplemented with CuSO(4) vs. pigs fed control diets
      but total liver GSH did not differ (P = 0.11) between control and TBCC pigs.
      Hepatic mRNA of cytochrome c oxidase assembly protein 17 was less (P = 0.01) in
      CuSO(4) and tended to be less (P = 0.08) in TBCC pigs vs. control pigs.
      Expression of antioxidant 1 mRNA was greater (P = 0.04) in TBCC pigs and tended
      to be greater (P = 0.06) in CuSO(4) pigs compared with control pigs. Results of
      this study indicated that, when fed at 225 mg Cu/kg diet, TBCC may cause less
      oxidative stress in the duodenum than CuSO(4). Feeding weanling pigs increased Cu
      resulted in modulation of certain Cu transporters and chaperones at the
      transcription level.

PMID- 22585804
TI  - Concentrations of analyzed or reactive lysine, but not crude protein, may predict
      the concentration of digestible lysine in distillers dried grains with solubles
      fed to pigs.
AB  - The objectives of this experiment were to evaluate procedures that may be used to
      predict the concentration of standardized ileal digestible (SID) Lys in
      distillers dried grains with solubles (DDGS) fed to pigs and to evaluate the
      accuracy of a published equation to predict SID Lys in DDGS. Twenty-one sources
      of DDGS were analyzed (as-fed basis) for CP (23.8% to 33.6%; CV = 8.3%), Lys
      (0.69% to 1.17%; CV = 12.4%), and furosine (0.02% to 0.22%; CV = 91.4%). The
      concentration of reactive Lys (%, as-fed basis) was calculated as analyzed Lys
      (%) - furosine (%) / 0.32 * 0.40 and ranged from 0.47% to 1.15% (CV = 20.7%) in
      the 21 sources of DDGS. Twenty-one diets that each contained 60.0% of 1 source of
      DDGS as the sole source of CP and AA were formulated. An N-free diet was also
      formulated and was used to determine basal endogenous losses of CP and AA. Twenty
      two barrows with an initial BW of 45.2 kg (SD = 3.1 kg) were fitted with a T
      cannula in the distal ileum and allotted to a 22 * 10 Youden square design with
      the 22 diets and 10 periods. The SID of CP and AA were calculated for each source
      of DDGS. The SID of CP ranged from 69.8% to 79.6%, and the SID of Lys ranged from
      45.3% to 74.1%. The concentration of SID Lys in the 21 samples of DDGS was highly
      related to the concentration of analyzed Lys (P < 0.001; r(2) = 0.849) and with
      the concentration of reactive Lys in the samples (P < 0.001; r(2) = 0.898). In
      contrast, the concentration of SID Lys in the 21 sources of DDGS was not related
      to the concentration of CP in the samples (P = 0.558; r(2) = 0.021). However,
      values for SID Lys were in good agreement with values predicted using a published
      prediction equation. In conclusion, analyzed Lys in DDGS, but not CP, may be used
      to predict the concentration of SID Lys in DDGS fed to pigs. However, analysis of
      furosine in addition to Lys and subsequent calculation of reactive Lys improve
      the prediction accuracy of digestible Lys concentration in DDGS.

PMID- 22585805
TI  - Direct and maternal genetic effects for body weight and price of calves sold for
      veal production.
AB  - The aim of this study was to estimate direct and maternal genetic parameters for
      age at sale (AS, d), BW (kg), price (PR, ?/kg), and market value (MV, ?/calf) of
      Brown Swiss male calves (Bos taurus) from first- (n = 6,719) and second- (n =
      4,405) parity dams marketed at livestock auctions from 2003 to 2007, and destined
      for veal production. Market value was calculated as the product of PR and BW.
      Restricted maximum likelihood procedures incorporating multiple trait animal
      models were used to infer genetic parameters for AS, BW, and PR, whereas
      estimates for MV were from single trait models. Bivariate analyses treating
      performance of calves from first- and second-parity cows as different traits were
      also performed. Direct heritabilities for AS, BW, and cattle prices ranged from
      0.046 to 0.090, 0.078 to 0.130, and 0.064 to 0.152, respectively, and the
      corresponding maternal heritabilities varied from 0.020 to 0.030, 0.036 to 0.079,
      and 0.020 to 0.045, respectively. Direct genetic correlations between the traits
      were generally moderate to high and negative, whereas direct-maternal
      relationships were moderate to low. Genetic correlation between the same trait
      recorded on calves from first- and second-parity dams was less than unity, but
      generally high and positive, suggesting that AS, BW, PR, and MV can be treated as
      the same traits across parities. As calf price is routinely collected at auctions
      and shows genetic variation, it can be genetically improved.

PMID- 22585806
TI  - Plasma progesterone concentration in beef heifers receiving exogenous glucose,
      insulin, or bovine somatotropin.
AB  - Three experiments were conducted to evaluate plasma concentrations of glucose,
      insulin, IGF-I, and progesterone (P4) in pubertal beef heifers receiving
      exogenous glucose, insulin, or sometribove zinc. All heifers used had no luteal
      P4 synthesis but received a controlled internal drug-releasing device containing
      1.38 g of P4 to estimate treatment effects on hepatic P4 degradation. In Exp. 1,
      8 pubertal, nulliparous Angus * Hereford heifers (initial BW = 442 +/- 14 kg;
      initial age = 656 +/- 7 d) were randomly assigned to receive, in a crossover
      design containing 2 periods of 10 h, intravenous (i.v.) infusions (10 mL) of
      insulin (1 MUg/kg of BW; INS) or saline (0.9%; SAL). Treatments were administered
      via jugular venipuncture in 7 applications (0.15 MUg insulin/kg BW per
      application) 45 min apart (from 0 to 270 min). Blood samples were collected
      immediately before each infusion as well as at -120, -60, 330, 390, and 450 min
      relative to the first infusion. Heifers receiving INS had greater (P < 0.01)
      plasma insulin, reduced (P <= 0.04) plasma glucose and IGF-I, and similar (P =
      0.62) plasma P4 concentrations compared with SAL heifers. In Exp. 2, the same
      heifers were assigned to receive, in a similar experimental design as Exp. 1,
      i.v. infusions (10 mL) of 1) insulin (1 MUg/kg BW) and glucose (0.5 g/kg BW;
      INS+G) or 2) SAL. Heifers receiving INS+G had greater (P <= 0.02) plasma insulin,
      glucose, and P4 but reduced (P = 0.01) plasma IGF-I concentrations compared with
      SAL heifers. In Exp. 3, the same heifers were assigned to receive, in a crossover
      design containing 2 periods of 14 d, subcutaneous (s.c.) injections of 1) 250 mg
      of sometribove zinc (BST) or 2) SAL. Blood samples were collected 3 h apart
      (0900, 1200, 1500, and 1800 h) from heifers on d 6, 8, and 10 relative to
      treatment administration (d 1). Heifers receiving BST had greater (P < 0.01)
      plasma glucose and IGF-I and similar (P >= 0.67) plasma insulin and P4
      concentrations compared with SAL heifers. Results from this series of experiments
      suggested that concurrent increases in glucose and insulin are required to reduce
      hepatic catabolism and increase plasma concentrations of P4 in bovine females.

PMID- 22585807
TI  - Genetic associations between flight speed and growth traits in Nellore cattle.
AB  - The aim of the present study was to estimate genetic parameters for flight speed
      and its association with growth traits in Nellore beef cattle. The flight speed
      (FS) of 7,402 yearling animals was measured, using a device composed of a pair of
      photoelectric cells. Time interval data (s) were converted to speed (m/s) and
      faster animals were regarded as more reactive. The growth traits analyzed were
      weaning weight (WW), ADG from weaning to yearling age, and yearling scrotal
      circumference (SC). The (co)variance components were estimated using REML in a
      multitrait analysis applying an animal model. The model included random direct
      additive genetic and residual effects, fixed effects of contemporary groups, age
      of dam (classes), and age of animal as covariable. For WW, the model also
      included maternal genetic and permanent environmental random effects. The direct
      heritability estimate for FS was 0.26 +/- 0.05 and direct heritability estimates
      for WW, SC, and ADG were 0.30 +/- 0.01, 0.48 +/- 0.02, and 0.19 +/- 0.01,
      respectively. Estimates of the genetic correlation between FS and the growth
      traits were -0.12 +/- 0.07 (WW), -0.13 +/- 0.08 (ADG), and -0.11 +/- 0.07 (SC).
      Although the values were low, these correlations showed that animals with better
      temperaments (slower FS) tended to present better performance. It is possible to
      infer that longterm selection for weight and scrotal circumference can promote a
      positive genetic response in the temperament of animals. Nevertheless, to obtain
      faster genetic progress in temperament, it would be necessary to perform direct
      selection for such trait. Flight speed is an easily measured indicator of
      temperament and can be included as a selection criterion in breeding programs for
      Nellore cattle.

PMID- 22585808
TI  - Influence of thermal environment on sows around farrowing and during the
      lactation period.
AB  - Our objective was to investigate the effects of floor heating duration (HEAT: 35
      degrees c for 12 or 48 h) after birth of first piglet (BFP) under different room
      temperatures (ROOM: 15 degrees C, 20 degrees C, 25 degrees C) on sows during
      farrowing and lactation. The study included 8 to 11 repetitions for each
      combination of ROOM and HEAT. There were no treatment effects on indicators of
      birth problems (duration of parturition, interbirth intervals, umbilical cord
      lactate concentration), BW changes of the sow, and litter size and weight until
      weaning. Sows at 15 degrees C compared with 20 degrees C and 25 degrees C spent
      more time nest building (P = 0.015). The feed intake was reduced the first 7 d
      after farrowing in sows at 25 degrees C (P = 0.014); however, both daily feed
      intake (P = 0.018) and water consumption (P < 0.001) of these warm sows exceeded
      that at lower temperatures during the last part of the lactation. Sows at 15
      degrees C received more medical treatments until weaning at heat = 48 h only
      (ROOM and HEAT interaction, P = 0.005). Room temperature influenced prefarrowing
      water consumption (25 degrees C > 20 degrees C and 15 degrees C; P < 0.017), sow
      surface temperature (15 degrees C < 20 degrees C < 25 degrees C; P < 0.001),
      respiration rate (25 degrees C > 20 degrees C > 15 degrees C; P < 0.001), and
      rectal temperature during the first 12 h after bfp (15 degrees C < 25 degrees C;
      P = 0.009); additionally, long floor heating duration (HEAT = 48 h) increased the
      respiration rate by 50% d 1 and 2 after bfp (p < 0.001). The proportion of lying
      time on the unheated slatted floor increased with room temperature (P < 0.001)
      and, transiently, also for the heat = 48 h treatment 13 to 48 h after BFP (P <
      0.001). The majority of piglets (82% to 95%) were born on the heated solid floor,
      regardless of room temperature (P = 0.46). Sows spent approximately twice as much
      time standing and walking at 15 degrees C during 13 to 48 h after BFP at HEAT =
      12 h only (ROOM and HEAT interaction; P = 0.002). In conclusion, long-term
      indicators of reduced sow performance were unaffected by room temperature,
      probably because the farrowing and lactating sows in the current pen design were
      able to perform thermoregulatory behavior and successfully adapt to room
      temperatures between 15 degrees C and 25 degrees C.

PMID- 22585809
TI  - Characterizing bovine adipocyte distribution and its relationship with carcass
      and meat characteristics using a finite mixture model.
AB  - The appreciation of adipose tissue complexity has initiated a new era of
      multifaceted investigations that continue to provide findings in adipocyte
      biology, but quantitative descriptions of adipocyte distribution are lacking. The
      first objective was to develop a finite mixture model to model adipocyte bimodal
      distribution and to correlate these estimates with carcass and meat
      characteristics. A secondary objective was to demonstrate within-animal observed
      variability in adipocyte cellularity. Steers were finished on a high-grain diet
      (n = 14) or grass (n = 16). One 12-cm thick LM steak from each steer was
      collected during harvest. A probability density function was developed that
      partitioned the cell diameter population into small and large populations and
      described the relative proportions of cells for each animal in these 2 distinct
      populations. Five parameters were estimated through the finite mixture model: the
      means (MU(1) and MU(2)) and SD (sigma(1) and sigma(2)) for the small and large
      adipocyte populations, respectively, and a proportion parameter (p) describing
      the proportion of the distribution of the smaller adipocyte populations. The
      proportion parameter for all animals tended to be different (P = 0.07) between
      groups with the grain presenting a p of 22.5 +/- 12.5% and grass 16.2 +/- 4.7%.
      The MU(2) was correlated with yield grade (YG, P = 0.04), and sigma(2) with final
      BW, HCW, dressing percentage, YG, and quality grade score (P = 0.01). When
      correlating these parameters with the sensory data, MU(2) and sigma(2) were
      correlated with tenderness (P <= 0.05), sigma(1) and p with juiciness (P <=
      0.05), and p with overall palatability (P = 0.01). Adipocyte cellularity
      variability was measured by examining the results from 5 randomly chosen steers
      from each group (grain and grass). In this subset, the MU(1) and p ranged from
      32.1 to 46.1 MUm and 1 to 27% for grass-finished steers, and ranged from 33.7 to
      41.0 MUm and 10 to 48% for grain-finished steers. The MU(2) and (1 - p) ranged
      from 75.0 to 105.1 MUm and 73 to 99% for grass-finished steers, respectively, and
      ranged from 84.8 to 124.0 MUm and 52 to 90% for grain-finished steers,
      respectively. The finite mixture model provides a quantitative description of the
      distribution of adipocytes and contributes to explaining adipocyte biology.
      Adipocyte cellularity variability among samples within an animal is a topic that
      should be further evaluated, as well as its correlation with other factors, such
      as gene expression and hormone secretion.

PMID- 22585810
TI  - Genotype by region and season interactions on weaning weight in United States
      Angus cattle.
AB  - The objective of this study was to determine if weaning weight performance is
      genetically consistent across different environments in the United States. The
      American Angus Association provided weight and pedigree data. Weaning weights
      observed in the Southeast (SoE) and Northwest (NW) were the focus of this study,
      as these regions are perceived as opposite extremes in climate. The 2 most
      represented calving seasons in each region were fall and winter in the SoE and
      winter and spring in the NW. The original data were edited to remove weaning
      weight records outside of 3 SD from the respective region-season mean,
      contemporary groups smaller than 20, and single-sire contemporary groups. The
      final dataset included 884,465 weaning weight records with 64,907 from fall-born
      calves in the SoE, 74,820 from winter-born calves in the SoE, 346,724 from winter
      born calves in the NW and 398,014 from spring-born calves in the NW. Weaning
      weights of calves born in different region-season classes adjusted to 205 d of
      age were considered different but genetically correlated traits in a multivariate
      analysis. The sole fixed effect was weaning contemporary group and random effects
      included direct, maternal, maternal permanent environment, and a residual. Direct
      heritability estimates differed little across environments: 0.31 and 0.35 for
      weight in fall- and winter-born calves in the SoE, and 0.29 and 0.32 for winter-
      and spring-born calves in NW. Maternal heritability estimates ranged from 0.12 in
      the NW to 0.16 the SoE. Genetic correlations spanned from 0.69 to 0.93 among
      direct effects and from 0.65 to 0.95 among maternal effects. All heritability
      estimates had small (0.01 to 0.04) SE. The most distinct environments appeared to
      be winter in SoE and spring in NW (correlations of 0.69 and 0.65 for the direct
      and maternal effects). Different choices of sires for different environments
      might be justified to achieve the growth performance expected.

PMID- 22585811
TI  - Effects of establishment method and fall stocking rate of wheat pasture on forage
      mass, forage chemical composition, and performance of growing steers.
AB  - Stocking rate is a fundamental variable for managing pastures, and there is a
      distinct relationship between stocking rate and animal performance for each
      forage type. This research was conducted to determine the effects of fall
      stocking rate (SR) and method of establishment of wheat pasture planted into
      dedicated crop fields on animal performance during the fall and subsequent
      spring. There was a factorial arrangement of tillage methods used in the
      establishment of wheat pasture and fall stocking rates. Tillage treatments
      included 1) CT, seed sown into a prepared seedbed, 2) RT, a single pass with a
      light disk followed by broadcasting of seed, or 3) NT, direct seeding into the
      undisturbed stubble of the grazed-out wheat pasture from the previous year. The
      fixed SR during the fall were 1.9, 2.5, and 3.7 growing beef steers (Bos taurus
      L.)/ha. In the spring all pastures were grazed at the same fixed SR by steers for
      graze out. Data were analyzed using the mixed procedure of SAS as a randomized
      complete block design with field as the experimental unit and year as the block.
      Forage mass, forage nutritive composition, and animal performance during the fall
      or spring were not affected (P >= 0.14) by tillage method. During the fall
      grazing season, with increasing SR there were linear (P < 0.01) decreases in BW
      of steers upon removal from pasture, BW gain per steer, and ADG, whereas grazing
      day per hectare and BW gain per hectare increased linearly (P < 0.01) with
      increasing SR. The carryover effects of fall SR into the spring grazing season
      decreased (P< 0.01) grazing-day per hectare and tended (P <= 0.09) to produce
      quadratic changes in BW upon removal from pasture and BW gain per hectare. Across
      the fall and spring grazing seasons, grazing-day per hectare increased linearly
      (P < 0.01) with greater SR, and BW gain per hectare increased quadratically (P =
      0.02) with increased fall SR. A tillage treatment by fall SR interaction (P =
      0.10) indicates that although there was no difference (P >= 0.12) due to tillage
      treatment in BW gain per hectare at 1.9 or 2.5 SR, NT fields produced (P <= 0.04)
      more BW gain per hectare than CT or RT at the 3.7 SR. Although increasing SR of
      growing steers leads to reduced animal performance in the fall and reduced
      carrying capacity in the spring, NT appears to be capable of withstanding greater
      fall SR with less impact on total production per hectare than CT or RT.

PMID- 22585812
TI  - Impact of selection for residual feed intake on breeding soundness and
      reproductive performance of bulls on pasture-based multisire mating.
AB  - There is concern in the beef industry that selecting bulls for feed efficiency
      based on residual feed intake (RFI) may have a negative impact on bull
      reproductive performance and fertility. Here we investigated the impact of
      selection of bulls for low RFI on breeding soundness evaluation (BSE),
      reproductive performance, and fertility of bulls under natural service in
      multisire mating groups on pasture. Of the 412 RFI-tested bulls available, 98
      (23.8%) were culled for performance, type, temperament, or other reasons, and 88
      (21.4%) were culled for failing BSE, for an overall cull rate of 45.1%. From
      among the 314 bulls subjected to BSE, 32 (10.2%), 20 (6.4%), and 36 (11.4%) were
      culled for poor feet and legs, scrotal circumference, and semen quality,
      respectively. The BSE traits were not different (P > 0.10) between bulls
      categorized as either inefficient (+RFI) or efficient (-RFI), but the proportion
      of bulls that failed to meet the 60% minimum sperm motility requirement tended (P
      = 0.07) to be greater in the -RFI group than in the +RFI group (10.2% vs. 4.4%,
      respectively). In a subpopulation of 115 bulls, individual progressive sperm
      motility was greater (P < 0.05) in +RFI (85%) than -RFI (80%) bulls. A multisire
      natural mating experiment was conducted during 2 consecutive breeding seasons
      (2006 to 2007 and 2007 to 2008) using 18 +RFI and 18 -RFI bulls. The overall
      calving rate (calves born/cows exposed) was 72.9%. Mean number of progeny per
      sire was significantly greater (P < 0.01) in -RFI bulls (18.3) than in +RFI bulls
      (11.8). Selection for feed efficiency based on RFI appears to have no detrimental
      impact on reproductive performance and fertility in beef bulls bred in multisire
      groups on pasture. However, the decreased sperm motility and the greater number
      of progeny per sire associated with -RFI status need further investigation.

PMID- 22585814
TI  - Modeling the relationships between quality and biochemical composition of fatty
      liver in mule ducks.
AB  - The fatty liver of mule ducks (i.e., French "foie gras") is the most valuable
      product in duck production systems. Its quality is measured by the technological
      yield, which is the opposite of the fat loss during cooking. The purpose of this
      study was to determine whether biochemical measures of fatty liver could be used
      to accurately predict the technological yield (TY). Ninety-one male mule ducks
      were bred, overfed, and slaughtered under commercial conditions. Fatty liver
      weight (FLW) and biochemical variables, such as DM, lipid (LIP), and protein
      content (PROT), were collected. To evaluate evidence for nonlinear fat loss
      during cooking, we compared regression models describing linear and nonlinear
      relations between biochemical measures and TY. We detected significantly greater
      (P = 0.02) linear relation between DM and TY. Our results indicate that LIP and
      PROT follow a different pattern (linear) than DM and showed that LIP and PROT are
      nonexclusive contributing factors to TY. Other components, such as carbohydrates,
      other than those measured in this study, could contribute to DM. Stepwise
      regression for TY was performed. The traditional model with FLW was tested. The
      results showed that the weight of the liver is of limited value in the
      determination of fat loss during cooking (R(2) = 0.14). The most accurate TY
      prediction equation included DM (in linear and quadratic terms), FLW, and PROT
      (R(2) = 0.43). Biochemical measures in the fatty liver were more accurate
      predictors of TY than FLW. The model is useful in commercial conditions because
      DM, PROT, and FLW are noninvasive measures.

PMID- 22585815
TI  - Body weight and body condition of breeding rabbits in commercial units.
AB  - Live BW and BCS data were collected from 2,775 breeding rabbits (644 males and
      2,131 females) of 34 genetic types and sorted according to their specialization
      (maternal, paternal, and others). Data were gathered on 66 visits to 43
      commercial farms in Spain between 2009 and 2011. Mean BW was 4.72 kg (range of
      2.87 to 8.13 kg, with a median BW of 4.60 kg) and mean BCS was 4.6 (range of 1.0
      to 9.0, with a median BCS of 5.0). females had heavier (P < 0.05) BW than males
      and paternal lines of rabbits had greater (P < 0.05) BW than maternal lines and
      other breeds/lines not selected for meat production. Between 69.3% and 75.4% of
      the rabbits were deemed healthy by a veterinarian and, as expected, healthy
      rabbits were heavier (P < 0.05) than sick rabbits diagnosed with rhinitis,
      mastitis, sore hocks, and several other diseases. Among purebred, maternal lines
      of rabbits, Hyplus GD24, UPV A, and UPV V were heavier (P < 0.05) than hyplus
      GD14 and Hyla HL-D lines, and line UPV R had the greatest (P < 0.05) BW among the
      purebred, paternal lines. Additionally, A*H, A*V, PS19, and P*A crossbreds had
      greater (P < 0.05) BW than HE-C*D, HL-C*D, H*V, LP*V, and V*P crossbreds among
      the maternal lines, whereas HE-SL were the heaviest (P < 0.05) crossbred paternal
      line of rabbits. Additionally, females received greater (P < 0.05) BCS than males
      and BCS were greater (P < 0.05) in healthy than sick rabbits. Moreover, maternal
      lines had smaller (P < 0.05) BCS than either paternal lines or other lines/breeds
      not selected for meat production. Results also indicated a moderate relationship
      between BCS and BW (r = 0.32), with a 1-point change in BCS equivalent to an ~
      245-g change in BW. results from this study can be used as baseline figures for
      breeding rabbits in spain and are essential factors in several decisions
      concerning housing, feeding, reproduction, health, and welfare of breeding
      rabbits.

PMID- 22585816
TI  - Effect of amino acids supply in reduced crude protein diets on performance,
      efficiency of mammary uptake, and transporter gene expression in lactating sows.
AB  - To test the hypothesis that reduction in dietary CP concentration coupled with
      crystalline AA inclusion increases the efficiency of AA use for milk production,
      mammary AA arteriovenous concentration differences (A-V), AA transport efficiency
      (A-V/A * 100), and transcript abundance of AA transporters and milk protein genes
      were determined in lactating sows fed 1 of 3 diets containing 9.5% (Deficient),
      13.5% (Ideal), or 17.5% (Standard) CP, with a similar profile of indispensable
      and dispensable AA. On d 7 and 18, arterial and mammary venous blood and mammary
      tissue were sampled postfeeding. Transcript abundance of AA transporters b(0,+)AT
      (SLC7A9), y(+)LAT2 (SLC7A6), ATB(0,+) (SLC6A14), CAT-1 (SLC7A1), and CAT-2b
      (SLC7A2) and milk protein beta-casein (CSN2) and LALBA (alpha-lactalbumin) were
      determined using reverse transcription quantitative PCR. Piglet ADG increased
      curvilinearly (linear and quadratic, P < 0.03) with increasing percent CP from
      Deficient to Standard. On d 7, Lys and Arg A-V and transport efficiency increased
      quadratically (P < 0.05) with increasing percent CP. On d 18, Lys A-V tended to
      increase (linear, P = 0.08) with increasing percent CP. Increasing CP increased
      Ile and Val A-V on d 7 (linear, P = 0.05 and P = 0.08, respectively) and Leu and
      Val on d 18 (linear, P = 0.07 and P = 0.04, respectively). On d 7, plasma
      concentrations of branched chain AA (BCAA):Lys decreased quadratically (P <
      0.05). Expression of genes SLC7A9, SLC7A6, SLC6A14, SLC7A1, SLC7A2, CSN2, and
      LALBA was unaffected by diet. In conclusion, decreasing the dietary CP from 17.5%
      to 13.5% with inclusion of crystalline AA did not affect piglet ADG, AA
      transporter, or milk protein gene expression but increased mammary transport
      efficiency and A-V of Lys and Arg on d 7 of lactation. This increase was
      associated with a decrease in plasma concentration of BCAA:Lys, suggesting a
      competitive mechanism between cationic and BCAA for transport of AA across
      mammary cells.

PMID- 22585818
TI  - Comparison of in vitro and in situ methods in evaluation of forage digestibility
      in ruminants.
AB  - The objective of this study was to compare the application of different in vitro
      and in situ methods in empirical and mechanistic predictions of in vivo OM
      digestibility (OMD) and their associations to near-infrared reflectance
      spectroscopy spectra for a variety of forages. Apparent in vivo OMD of silages
      made from alfalfa (n = 2), corn (n = 9), corn stover (n = 2), grass (n = 11),
      whole crops of wheat and barley (n = 8) and red clover (n = 7), and fresh alfalfa
      (n = 1), grass hays (n = 5), and wheat straws (n = 5) had previously been
      determined in sheep. Concentrations of indigestible NDF (iNDF) in all forage
      samples were determined by a 288-h ruminal in situ incubation. Gas production of
      isolated forage NDF was measured by in vitro incubations for 72 h. In vitro
      pepsin-cellulase OM solubility (OMS) of the forages was determined by a 2-step
      gravimetric digestion method. Samples were also subjected to a 2-step
      determination of in vitro OMD based on buffered rumen fluid and pepsin. Further,
      rumen fluid digestible OM was determined from a single 96-h incubation at 38
      degrees C. Digestibility of OM from the in situ and the in vitro incubations was
      calculated according to published empirical equations, which were either forage
      specific or general (1 equation for all forages) within method. Indigestible NDF
      was also used in a mechanistic model to predict OMD. Predictions of OMD were
      evaluated by residual analysis using the GLM procedure in SAS. In vitro OMS in a
      general prediction equation of OMD did not display a significant forage-type
      effect on the residuals (observed - predicted OMD; P = 0.10). Predictions of OMD
      within forage types were consistent between iNDF and the 2-step in vitro method
      based on rumen fluid. Root mean square error of OMD was least (0.032) when the
      prediction was based on a general forage equation of OMS. However, regenerating a
      simple regression for iNDF by omitting alfalfa and wheat straw reduced the root
      mean square error of OMD to 0.025. Indigestible NDF in a general forage equation
      predicted OMD without any bias (P >= 0.16), and root mean square error of
      prediction was smallest among all methods when alfalfa and wheat straw samples
      were excluded. Our study suggests that compared with the in vitro laboratory
      methods, iNDF used in forage-specific equations will improve overall predictions
      of forage in vivo OMD. The in vitro and in situ methods performed equally well in
      calibrations of iNDF or OMD by near-infrared reflectance spectroscopy.

PMID- 22585819
TI  - Effect of dietary omega-3 fatty acids on red blood cell lipid composition and
      plasma metabolites in the cockatiel, Nymphicus hollandicus.
AB  - Although dietary n-3 fatty acids have been extensively studied in poultry, they
      have not yet been prospectively investigated in psittacines, despite potential
      benefits for preventing and treating atherosclerosis, osteoarthritis, and other
      chronic disease processes. The objectives of this study were to investigate the
      incorporation of dietary n-3 fatty acids into red blood cells (RBC) and to
      determine the effects of supplementation of psittacine diets with fish or flax
      oil on plasma lipids and lipoproteins in the cockatiel. Adult cockatiels were fed
      a custom-formulated diet containing either 4% (wt/wt, as-fed) beef tallow (CON),
      3% fish oil + 1% tallow (FSH), or 3.5% flax oil + 0.5% tallow (FLX; n = 20 per
      diet group). Baseline measurements were obtained for RBC fatty acid composition,
      triacylglycerides (TAG), and cholesterol. After 8 to 13 wk on the study diets,
      plasma chemistry profiles, lipoprotein density profiles, and RBC fatty acid
      composition were determined. At 8 wk, total plasma cholesterol was least in FSH
      birds (P < 0.05) and TAG concentrations were less in FSH birds than FLX birds (P
      < 0.05). Total n-3 fatty acids, docosahexaenoic acid, docosapentaenoic acid, and
      eicosapentaenoic acid were markedly greater in the RBC of FSH birds than FLX or
      CON birds (P < 0.05). Alpha linolenic acid was greatest in FLX (P < 0.05).
      Initial and final BW, and nonlipid plasma chemistry values did not differ among
      diet groups. No adverse effects of dietary supplementation of cockatiels with
      3.5% flax oil or 3% fish oil were observed during the 13-wk feeding period.
      Although fish and flax oils provided similar total n-3 PUFA to the diets, fish
      oil caused greater reductions in cholesterol and TAG, and greater total RBC n-3
      incorporation. Thus, dietary modification of psittacine diets with long chain n-3
      PUFA from fish oil appears safe and may be beneficial to these long-lived
      companion birds.

PMID- 22585820
TI  - An economic evaluation of estrous synchronization and timed artificial
      insemination in suckled beef cows.
AB  - Partial budget analysis was used to determine the economic outcome of estrus
      synchronization (ES) and timed artificial insemination (TAI) in commercial cow
      calf production. Suckled beef cows (n = 1,197) from 8 locations were assigned
      randomly within each location to 1 of 2 treatment groups: 1) cows were
      inseminated artificially after synchronization of ovulation using the CO-Synch +
      CIDR protocol, which includes a 100-MUg injection of GnRH (OvaCyst; TevaAnimal
      Health, St. Joseph, MO) when a controlled internal drug-releasing device (CIDR;
      Pfizer Animal Health, New York, NY) containing 1.38 g of progesterone was
      inserted. The CIDR was removed 7 d later, and cows received a 25-mg injection of
      PGF(2alpha) (PGF; Lutalyse; Pfizer Animal Health), followed in 66 h with TAI and
      a second 100-MUg injection of GnRH (TAI; n = 582), and 2) cows were exposed to
      natural service (NS) without estrous synchronization (Control; n = 615). Within
      each herd, cows from both treatments were maintained together in similar pastures
      and were exposed to bulls 12 h after the last cow in the TAI treatment was
      inseminated. Overall, the percentage of cows exposed to treatments that
      subsequently weaned a calf was greater (P < 0.05) for TAI (84%) than Control
      (78%) cows. In addition, survival analysis demonstrated that cumulative calving
      distribution differed (P < 0.05) between the TAI and Control treatments. Weaning
      weights per cow exposed to treatments were greater (P < 0.01) for cows in the TAI
      treatment (193.4 +/- 4.3 kg) than those cows in the Control treatment (175.9 +/-
      4.3 kg). Overall, increased returns plus decreased costs ($82.32) minus decreased
      returns plus increased costs ($33.18) resulted in a $49.14 advantage per exposed
      cow in the TAI treatment compared with the Control treatment. Location greatly
      influenced weaned calf weights, which may have been a result of differing
      management, nutrition, genetic selection, production goals, and environments. We
      concluded that ES and TAI had a positive economic impact on subsequent weaning
      weights of exposed cows.

PMID- 22585821
TI  - Using real-time ultrasound and carcass measurements to estimate total internal
      fat in beef cattle over different breed types and managements.
AB  - The objective of this study was to re-evaluate our previously published technique
      of estimating total physically separable internal fat (IFAT) in beef cattle using
      real-time ultrasound (RTU) and carcass measurements from live animals by
      including more breed types and genders under different management scenarios. We
      expanded the original database and performed additional analyses. The database
      was gathered from 4 studies and contained 110 animals (16 bulls, 16 heifers, and
      78 steers), being Angus (n = 56), Angus* 5/8 Angus * 3/8 Nellore (n = 18), and
      Angus crossbreds (n = 36). Ultrasound measurements were obtained 7 d before
      slaughter, including the 12th to 13th rib fat thickness (uBF) and ultrasound
      kidney fat depth (uKFd). The uKFd was measured in a cross-sectional image
      collected between the first lumbar and 13th rib as previously published. Carcass
      data were collected 48 h post-mortem and consisted of backfat thickness (cBF),
      kidney fat depth (cKFd) and KPH weight, live BW, and HCW. Whole gastrointestinal
      tracts were removed and dissected to obtain IFAT weights. Weight of IFAT was
      highly correlated with KPH weight (0.88) and cKFd (0.81) and moderately
      correlated with uKFd (0.71). Prediction equations were developed for estimating
      IFAT, KPH weight, and cKFd with the PROC REG of SAS using the stepwise statement.
      The best predictors of IFAT were KPH weight or cKFd and cBF (r(2) = 0.84 and 0.83
      and root mean square errors (RMSE) of 4.23 and 4.33 kg, respectively). Ultrasound
      measurements of uKFd and uBF had an r(2) of 0.65 and RMSE of 6.07 kg when both
      were used to predict IFAT. The results of cross-validation analyses indicated
      that equations developed either with KPH weight or cKFd weight and cBF had
      greater precision than the equation developed with uKFd and uBF. Most of the
      errors associated with the mean square error of prediction were due to random,
      uncontrolled variation. These results were consistent with previously published
      evaluation of this technique. These findings confirm that this RTU technique
      allows the measurement of IFAT in a non-invasive way that may improve our ability
      to estimate IFAT in beef cattle, be used to more accurately formulate rations,
      and be applied in sorting cattle at feedyard.

PMID- 22585822
TI  - Providing a diet deficient in valine but with excess leucine results in a rapid
      decrease in feed intake and modifies the postprandial plasma amino acid and alpha
      keto acid concentrations in pigs.
AB  - Indispensable AA are involved in the control of feed intake. When a diet
      deficient in Val is offered to pigs, feed intake is typically reduced. This
      effect is aggravated when dietary Leu is supplied in excess of the requirement.
      If an unbalanced supply of branched-chain AA (BCAA) is harmful, an anorectic
      response may serve as a mechanism to prevent this situation. We verified this
      hypothesis by measuring the voluntary feed intake of a balanced diet offered
      during the 30-min period 1 h after ingestion of a test meal deficient or not in
      Val (Val- and Val+) with an excess of Leu. Twelve and four 6-wk-old crossbred
      female pigs were used in Exp. 1 and 2, respectively. Prior ingestion of the Val-
      test meal resulted in a 14% reduction in feed intake compared with that observed
      after ingestion of the Val+ test meal (P = 0.06) in Exp. 1, indicating that the
      signal to reduce feed intake occurred within 1 h. It is possible that the plasma
      concentration of the limiting AA serves as a signal for the dietary AA
      deficiency. We therefore determined the postprandial plasma concentrations of
      BCAA and their alpha-keto acids after ingestion of Val- and Val+ in 4 pigs in
      Exp. 2. After ingestion of the Val- diet, plasma concentrations of Val and its
      keto acid were reduced compared with values observed after ingestion of the Val+
      diet. The peak concentration occurred earlier after ingestion of the Val- diet
      compared with that of the Val+ diet. Although the plasma concentration increased
      after the meal, it declined rapidly in pigs offered Val-, and the Val
      concentration 4 h after ingestion of the meal was even less than that observed in
      the fasted state. In conclusion, it appears that the pig is able to detect a
      deficient supply of Val within 1 h after ingestion. The plasma concentration of
      Val or its concentration relative to the other BCAA during the postprandial
      period may act as a signal indicating the AA deficiency.

PMID- 22585823
TI  - Analysis of factors to predict piglet body weight at the end of the nursery
      phase.
AB  - In pig (Sus Scrofa) production, within-batch variation in bw gain of piglets
      during the nursery period (up to 10 wk of age) can be high and is of high
      economic importance. Homogeneity of BW within batches of animals is important as
      it influences the efficiency of use of the grower and finisher facilities, and
      provides an extra value for the fattening farms. In the current study, factors
      for a light BW at the end of the nursery period of pigs were determined by
      analyzing datasets from 3 different swine research centers in the Netherlands and
      France. The entire dataset contained information on 77,868 individual piglets
      born between 2005 and 2010. Body weight was determined at different time points
      over the pre- and post-weaning phase, and sex, season of birth, litter
      information (litter size at day of birth and after cross-fostering, number of
      piglets born alive per litter, number of total born littermates, sow parity
      number), cross-fostered animals (yes or no), and pen group size over the post
      weaning period were recorded. A risk factor analysis approach was used to analyze
      the datasets to determine factors that predict piglet bw at the end of the
      nursery period. Body weight at the end of the nursery period corrected for age
      was mainly determined by season (P < 0.001), birth weight (BiW, P < 0.001),
      weaning weight (WW, P < 0.001), and BW at 6 wk of age (P < 0.001). These
      variables were consistent among datasets and explained approximately 70% of the
      overall variation in BW at the end of the nursery period. Litter information did
      not significantly (P > 0.05) contribute to explaining the BW at the end of the
      nursery period. To discard the possibility of intrauterine growth retarded
      piglets (IUGR) being the reason for the influence of BiW as an explanatory factor
      in the regression model, a further analysis was performed on the effect of this
      category of piglets on the results of the regression analysis. Overall, it was
      concluded that the bw of piglets at the end of the nursery phase is mainly
      determined by season, sex, birth, WW, and BW at 6 wk of age. Piglets with a BiW
      greater than the mean biw minus 2.5 times the sd have the potential to compensate
      during the subsequent phases of growth.

PMID- 22585824
TI  - Application of a computer vision system to classify beef as normal or dark, firm,
      and dry.
AB  - The purpose of this research was to evaluate the possibility of using computer
      vision systems (CVS) to detect DFD beef. The experimental material consisted of
      beef obtained from 60 carcasses (M. semimembranosus) that were 48 h postmortem.
      The beef was classified into 2 quality groups according to pH: normal (pH < 5.8)
      or DFD (pH >= 5.8). L*, a*, and b* color components were determined in the
      experimental materials using both CIELab and a CVS using 3 color models: RGB
      (red, green, blue), HSV (hue, saturation, value), and HSL (hue, saturation,
      lightness). The total heme pigment content also was determined. As determined by
      both CIELab and CVS, DFD meat was characterized by a darker color than normal
      beef. Color lightness, as determined using both CIELab and CVS, can also be used
      to detect DFD beef. A significant relationship was found between V (r = -0.79)
      and L (r = -0.77) using CVS and pH, which is an indicator of DFD beef. This
      finding indicates the possibility of using these color components to assess the
      pH level of beef.

PMID- 22585825
TI  - The impact of endophyte-infected fescue consumption on digital circulation and
      lameness in the distal thoracic limb of the horse.
AB  - This experiment was conducted to evaluate if consumption of endophyte-infected
      fescue alters digital circulation in the distal thoracic limb of the horse and to
      assess if soundness of the hooves of horses is affected by consumption of
      endophyte-infected fescue. Twelve American Quarter Horses (mean initial BW 459 +/
      31 kg), 6 mares and 6 geldings, were used in this 90-d study that comprised high
      endophyte (E+) and low-endophyte (E-) treatment groups. Fescue seed was
      integrated into the E+ diet at a rate sufficient to bring total ergovaline to 200
      MUg/kg, and endophyte-free fescue seed was incorporated into the E- diet from d 0
      to 90. From d 30 to 60, native prairie hay was replaced with high- or low
      endophyte fescue hay, bringing total dietary ergovaline to 280 MUg/kg (E+) and 18
      MUg/kg (E-). From d 61 to 90, fescue seed was ground to decrease particle size.
      On d 0, 30, 60, and 90, Doppler ultrasonography and thermographic imaging were
      used to measure the diam. of the medial palmar artery, velocity of blood flow,
      and surface temperature of the hoof as indicators of digital circulation.
      Lameness examinations were conducted on the same days. There were no consistent
      treatment differences observed when evaluating measurements of digital
      circulation. On d 60, horses in the E+ treatment group showed increased hoof
      sensitivity in the left limb (P = 0.02). These horses tended to have increased
      hoof sensitivity when both thoracic limbs were averaged (P = 0.06), and they
      demonstrated increased lameness during longeing (P = 0.08). Data indicated that
      mares may have increased digital circulation, regardless of treatment, compared
      with geldings (P <= 0.05). Heavier horses also had greater arterial diam.,
      velocity of blood flow, and hoof temperature than lighter BW horses (P <= 0.05)
      on d 30, 60, and 90 at time points that ranged from 90 to 180 min after feeding.
      Although horses consuming the E+ diet demonstrated increased lameness, especially
      on d 60, compared with horses consuming the E- diet, the measures of digital
      circulation did not support the hypothesis that digital circulation was reduced.
      Because of observed lameness issues, limiting the access of horses to endophyte
      infected fescue may be prudent.

PMID- 22585826
TI  - Selection for ovulation rate in rabbits: direct and correlated responses
      estimated with a cryopreserved control population.
AB  - The aim of this work was to evaluate the response in 10 generations of selection
      for ovulation rate in rabbits using a cryopreserved control population. Selection
      was based on the phenotypic value of ovulation rate estimated at d 12 of second
      gestation by laparoscopy. To produce the control population, embryos from 50
      donor females and 18 males, belonging to the base generation of the line selected
      for ovulation rate, were recovered. A total of 467 embryos (72-h embryos) were
      vitrified and stored in liquid N(2) for 10 generations. The size of both
      populations was approximately 10 males and 50 females. The number of records used
      to analyze the different traits ranged from 99 to 340. Data were analyzed using
      Bayesian methodology. A difference between the selected and the control
      populations of 2.1 ova (highest posterior density interval (HPD(95%))[1.3, 2.9])
      was observed in ovulation rate (OR), but it was not accompanied by a correlated
      response in litter size (LS; -0.3; HPD(95%) [-1.1, 0.5]). The number of implanted
      embryos (IE) increased with selection in 1.0 embryo (HPD(95%) [-0.6, 2.0]), but
      this increase was not relevant. Prenatal survival, embryonic survival, and fetal
      survival (FS) were calculated as LS/OR, IE/OR, and LS/IE, respectively. Prenatal
      survival was reduced with selection (-0.12; HPD(95%) [-0.20, -0.04]), basically
      because of a decrease in FS (-0.12; HPD(95%) [-0.19, -0.06]). Embryonic survival
      could have slightly decreased (-0.05; HPD(95%) [-0.12, 0.02]). In summary,
      comparison with a control population showed that ovulation rate in rabbits
      increased with selection without any correlated response in litter size,
      basically because of a decrease in fetal survival.

PMID- 22585827
TI  - Neonatal piglet traits of importance for survival in crates and indoor pens.

PMID- 22585828
TI  - Tonic control of kisspeptin release in prepubertal monkeys: implications to the
      mechanism of puberty onset.
AB  - Previously we have shown that a reduction in gamma-amino butyric acid (GABA)
      inhibition is critical for the mechanism initiating puberty onset because chronic
      infusion of the GABA(A) receptor antagonist, bicuculline, significantly increased
      GnRH release and accelerated the timing of menarche and first ovulation in female
      rhesus monkeys. Because previous studies in our laboratory indicate that in
      prepubertal female monkeys, kisspeptin release in the medial basal hypothalamus
      is low, whereas kisspeptin-10 can stimulate GnRH release, we hypothesized that a
      low level of kisspeptin release prior to puberty onset is due to tonic GABA
      inhibition. To test this hypothesis we examined the effects of bicuculline
      infusion on kisspeptin release using a microdialysis method. We found that
      bicuculline at 1 MUM dramatically stimulates kisspeptin release in the medial
      basal hypothalamus of prepubertal monkeys but had little effect on kisspeptin
      release in midpubertal monkeys. We further examined whether bicuculline-induced
      GnRH release is blocked by the presence of the kisspeptin antagonist, peptide
      234. We found that inhibition of kisspeptin signaling blocked the bicuculline
      induced stimulation of GnRH release, suggesting that kisspeptin neurons may relay
      inhibitory GABA signals to GnRH neurons. This implies that a reduction in tonic
      GABA inhibition of GnRH release is, at least in part, mediated through kisspeptin
      neurons.

PMID- 22585829
TI  - Resveratrol stimulates cortisol biosynthesis by activating SIRT-dependent
      deacetylation of P450scc.
AB  - In the human adrenal cortex, cortisol is synthesized from cholesterol by members
      of the cytochrome P450 superfamily and hydroxysteroid dehydrogenases. Both the
      first and last steps of cortisol biosynthesis occur in mitochondria. Based on our
      previous findings that activation of ACTH signaling changes the ratio of
      nicotinamide adenine dinucleotide (NAD) phosphate to reduced NAD phosphate in
      adrenocortical cells, we hypothesized that pyridine nucleotide metabolism may
      regulate the activity of the mitochondrial NAD(+)-dependent sirtuin (SIRT)
      deacetylases. We show that resveratrol increases the protein expression and half
      life of P450 side chain cleavage enzyme (P450scc). The effects of resveratrol on
      P450scc protein levels and acetylation status are dependent on SIRT3 and SIRT5
      expression. Stable overexpression of SIRT3 abrogates the cellular content of
      acetylated P450scc, concomitant with an increase in P450scc protein expression
      and cortisol secretion. Mutation of K148 and K149 to alanine stabilizes the
      expression of P450scc and results in a 1.5-fold increase in pregnenolone
      biosynthesis. Finally, resveratrol also increases the protein expression of P450
      11beta, another mitochondrial enzyme required for cortisol biosynthesis.
      Collectively, this study identifies a role for NAD(+)-dependent SIRT deacetylase
      activity in regulating the expression of mitochondrial steroidogenic P450.

PMID- 22585831
TI  - Fructose-induced hypothalamic AMPK activation stimulates hepatic PEPCK and
      gluconeogenesis due to increased corticosterone levels.
AB  - Fructose consumption causes insulin resistance and favors hepatic gluconeogenesis
      through mechanisms that are not completely understood. Recent studies
      demonstrated that the activation of hypothalamic 5'-AMP-activated protein kinase
      (AMPK) controls dynamic fluctuations in hepatic glucose production. Thus, the
      present study was designed to investigate whether hypothalamic AMPK activation by
      fructose would mediate increased gluconeogenesis. Both ip and
      intracerebroventricular (icv) fructose treatment stimulated hypothalamic AMPK and
      acetyl-CoA carboxylase phosphorylation, in parallel with increased hepatic
      phosphoenolpyruvate carboxy kinase (PEPCK) and gluconeogenesis. An increase in
      AMPK phosphorylation by icv fructose was observed in the lateral hypothalamus as
      well as in the paraventricular nucleus and the arcuate nucleus. These effects
      were mimicked by icv 5-amino-imidazole-4-carboxamide-1-beta-d-ribofuranoside
      treatment. Hypothalamic AMPK inhibition with icv injection of compound C or with
      injection of a small interfering RNA targeted to AMPKalpha2 in the mediobasal
      hypothalamus (MBH) suppressed the hepatic effects of ip fructose. We also found
      that fructose increased corticosterone levels through a mechanism that is
      dependent on hypothalamic AMPK activation. Concomitantly, fructose-stimulated
      gluconeogenesis, hepatic PEPCK expression, and glucocorticoid receptor binding to
      the PEPCK gene were suppressed by pharmacological glucocorticoid receptor
      blockage. Altogether the data presented herein support the hypothesis that
      fructose-induced hypothalamic AMPK activation stimulates hepatic gluconeogenesis
      by increasing corticosterone levels.

PMID- 22585830
TI  - Uterine development and fertility are dependent on gene dosage of the nuclear
      receptor coregulator REA.
AB  - Although the effectiveness of nuclear hormone-receptor complexes is known to
      depend on coregulator partner proteins, relatively little is known about the
      roles of coregulators in uterine development and early stages of pregnancy and
      implantation. Because conventional genetic deletion of the coregulator, repressor
      of estrogen receptor activity (REA), was embryonic lethal, we here study REA
      conditional knockout mice generated by cre-loxP recombination, in which REA
      function was abrogated only in progesterone receptor-expressing tissues, to
      define the roles of REA in postembryonic stages and in a tissue-specific manner.
      We find that REA has gene dose-dependent activity impacting uterine development
      and fertility. Conditional homozygous mutant (REA(d/d)) mice developed to
      adulthood and showed normal ovarian function, but females were infertile with
      severely compromised uterine development and function characterized by cell cycle
      arrest, apoptosis, and altered adenogenesis (endometrial gland morphogenesis),
      resulting in failure of implantation and decidualization. By contrast, mice
      heterozygous for REA (REA(f/d)) had a very different phenotype, with estradiol
      treatment resulting in hyperstimulated, large uteri showing increased
      proliferation of luminal epithelial cells, and enhanced fluid imbibition
      associated with altered regulation of aquaporins. These REA(f/d) female mice
      showed a subfertility phenotype with reduced numbers and sizes of litters. These
      findings highlight that uterine development and regulation of estrogen receptor
      activities show a bimodal dependence on the gene dosage of REA. Optimal uterine
      development and functional activities require the normal gene dosage of REA, with
      partial or complete deletion resulting in hyperresponsiveness or
      underresponsiveness to hormone and subfertility or infertility, respectively.

PMID- 22585832
TI  - Characterization of the spinal nucleus of the bulbocavernosus neuromuscular
      system in male mice lacking androgen receptor in the nervous system.
AB  - Motoneurons in the spinal nucleus of the bulbocavernosus (SNB) and their target
      bulbocavernosus (BC) and levator ani (LA) muscles play a role in male copulation
      and fertility. Testosterone (T) induces sexual differentiation of this SNB
      neuromuscular system during development and maintains its activation in
      adulthood. In the rat, T-induced effects mostly involve the androgen receptor
      (AR). However, the role of central AR in T-induced effects remains to be studied
      with pertinent genetic models. We addressed this question by using specific
      motoneuron immunolabeling and retrograde tracing in mice selectively disrupted
      for AR in the nervous system. This work reveals that nervous system AR is not
      required either for T-induced development of BC-LA muscles and perinatal sparing
      of SNB motoneurons from atrophy or for adult sensitivity of BC-LA muscles to T.
      By contrast, loss of AR expression in the nervous system resulted in SNB
      motoneurons having smaller somata and shorter dendrites than controls. We studied
      the effects of adult castration and T supplementation on SNB cell morphology in
      control and mutant males; these experiments showed that central AR is involved in
      the developmental regulation of soma size and dendritic length and in the adult
      maintenance of soma size of SNB motoneurons. T seemed to act indirectly through
      BC-LA muscles to maintain dendritic length in adulthood. Our results also suggest
      that central AR functions may contribute to normal activity of SNB motoneurons
      and perineal muscles because mutant mice displayed diminished copulatory behavior
      and fertility.

PMID- 22585836
TI  - NHGRI beats a path to clinical genomics.

PMID- 22585835
TI  - 3D imaging spots cancer cells.

PMID- 22585837
TI  - Lab technique immortalizes cells.

PMID- 22585839
TI  - Q&A: Tom Curran on translational research.

PMID- 22585840
TI  - Finding new uses for existing medications.

PMID- 22585841
TI  - Cancer centers work to optimize pipelines.

PMID- 22585852
TI  - Another LAP in the race.
AB  - The unique promise of latency-associated peptide resides in its selective
      presence on regulatory T cells (Treg) in the activated setting after patients are
      treated with immunomodulators such as anti-CTLA-4. The improved ability to track,
      scrutinize, and potentially target Tregs in this manipulated environment will be
      increasingly critical in developing immune-based therapies for patients with
      cancer.

PMID- 22585853
TI  - New lung cancer susceptibility locus identified: significance and implications
      for other genome-wide association studies.
AB  - Genome-wide association studies have identified more than 150 loci that influence
      the risk of cancer. In this issue of Cancer Discovery, Shi and colleagues report
      that a variant in RAD52 is a risk factor for squamous cell lung carcinoma. This
      work is important not only for its potential implications on control of this
      dreaded malignancy but also for its methodologic contributions that can advance
      the field of molecular-genetic epidemiology.

PMID- 22585854
TI  - Regulating the TRAIL of destruction: how A20 protects glioblastomas from TRAIL
      mediated death.
AB  - In this issue of Cancer Discovery, Bellail and colleagues unravel how
      overexpression of the ubiquitin-modifying enzyme A20 results in TNF-related
      apoptosis-inducing ligand (TRAIL) resistance in glioblastoma. After TRAIL
      receptor stimulation, A20 mediates the polyubiquitination of RIP1 at the TRAIL
      receptor tail, resulting in the interaction of the polyubiquin chain to
      procaspase-8 that is recruited to the TRAIL-bound receptors. The inability of
      ubiquitin-bound procaspase-8 to be dimerized and activated prevents the execution
      of the apoptotic program.

PMID- 22585856
TI  - Cancers of the colon and rectum: identical or fraternal twins?
AB  - Colorectal cancer represents a major cause of cancer morbidity and mortality,
      with approximately 1.2 million cases and 600,000 deaths worldwide each year.
      Because of the anatomic continuity of the colon into the rectum, cancers
      affecting these organs have historically been considered equivalent. In this
      Prospective, we discuss the clinical and experimental data suggesting that colon
      cancer and rectal cancer are highly related, but distinct, diseases.
      Reconsidering the relationship between these cancers has implications for the
      development of new therapeutic paradigms.

PMID- 22585855
TI  - New roles opined for OPCML.
AB  - OPCML, frequently inactivated in ovarian tumors, mediates its antitumor effect
      via binding to the extracellular domains of several important oncogenic receptor
      tyrosine kinases (RTK). This, in turn, leads to the downregulation of RTKs in
      tumor cells and results in significant inhibition of tumor growth.

PMID- 22585857
TI  - Identification of human regulatory T cells in the setting of T-cell activation
      and anti-CTLA-4 immunotherapy on the basis of expression of latency-associated
      peptide.
AB  - Effector and regulatory T cells (Treg) share multiple markers that make it
      difficult to discern differences in these populations in humans. The
      transcription factor FoxP3 has been shown to identify Tregs. However, the
      detection of FoxP3 requires cell permeabilization, thereby preventing isolation
      of viable Tregs. Subsequently, the extracellular marker CD127 was established for
      the identification of Tregs. However, these studies were not conducted in the
      setting of immunotherapy. Here, we conducted studies to analyze CD127 and FoxP3
      expression on T cells before and after in vitro activation as well as in the
      setting of patients treated with antibodies directed against cytotoxic T
      lymphocyte antigen-4 (CTLA-4). We show that latency-associated peptide (LAP), as
      opposed to CD127, was capable of identifying Tregs after in vitro activation as
      well as after treatment with anti-CTLA-4. Therefore, we propose that LAP should
      be used as a marker of Tregs for immune monitoring studies in patients treated
      with active immunotherapy such as anti-CTLA-4. SIGNIFICANCE: Tregs play an
      important role in human diseases, including cancer and autoimmunity; however, it
      has been difficult to study these cells because of a lack of an appropriate
      marker. Here, we propose LAP as a marker that can be used to identify Tregs in
      patients treated with immunotherapy, thereby permitting isolation of these cells
      for functional studies and for ex vivo expansion.

PMID- 22585858
TI  - Inherited variation at chromosome 12p13.33, including RAD52, influences the risk
      of squamous cell lung carcinoma.
AB  - Although lung cancer is largely caused by tobacco smoking, inherited genetic
      factors play a role in its etiology. Genome-wide association studies in Europeans
      have only robustly demonstrated 3 polymorphic variations that influence the risk
      of lung cancer. Tumor heterogeneity may have hampered the detection of
      association signal when all lung cancer subtypes were analyzed together. In a
      genome-wide association study of 5,355 European ever-smoker lung cancer patients
      and 4,344 smoking control subjects, we conducted a pathway-based analysis in lung
      cancer histologic subtypes with 19,082 single-nucleotide polymorphisms mapping to
      917 genes in the HuGE-defined "inflammation" pathway. We identified a
      susceptibility locus for squamous cell lung carcinoma at 12p13.33 (RAD52,
      rs6489769) and replicated the association in 3 independent studies totaling 3,359
      squamous cell lung carcinoma cases and 9,100 controls (OR = 1.20, P(combined) =
      2.3 * 10(-8)). SIGNIFICANCE: The combination of pathway-based approaches and
      information on disease-specific subtypes can improve the identification of cancer
      susceptibility loci in heterogeneous diseases.

PMID- 22585859
TI  - A20 ubiquitin ligase-mediated polyubiquitination of RIP1 inhibits caspase-8
      cleavage and TRAIL-induced apoptosis in glioblastoma.
AB  - The TNF-related apoptosis-inducing ligand (TRAIL) apoptotic pathway has emerged
      as a therapeutic target for the treatment of cancer. However, clinical trials
      have proven that the vast majority of human cancers are resistant to TRAIL
      apoptotic pathway-targeted therapies. We show that A20-mediated ubiquitination
      inhibits caspase-8 cleavage and TRAIL-induced apoptosis in glioblastoma through 2
      signaling complexes. A20 is highly expressed in glioblastomas and, together with
      the death receptor 5 and receptor-interacting protein 1, forms a plasma membrane
      bound preligand assembly complex under physiologic conditions. Treatment with
      TRAIL leads to the recruitment of caspase-8 to the plasma membrane-bound
      preligand assembly complex for the assembly of a death-inducing signaling
      complex. In the death-inducing signaling complex, the C-terminal zinc finger
      (Znf) domain of the A20 ubiquitin ligase mediates receptor-interacting protein 1
      polyubiquitination through lysine-63-linked polyubiquitin chains, which bind to
      the caspase-8 protease domain and inhibit caspase-8 dimerization, cleavage, and
      the initiation of TRAIL-induced apoptosis in glioblastoma-derived cell lines and
      tumor-initiating cells. SIGNIFICANCE: These results identify A20 E3 ligase as a
      therapeutic target whose inhibition can overcome TNF-related apoptosis-inducing
      ligand resistance in glioblastoma and thus have an impact on ongoing clinical
      trials of TNF-related apoptosis-inducing ligand-targeted combination cancer
      therapies.

PMID- 22585860
TI  - The OPCML tumor suppressor functions as a cell surface repressor-adaptor,
      negatively regulating receptor tyrosine kinases in epithelial ovarian cancer.
AB  - Epithelial ovarian cancer is the leading cause of death from gynecologic
      malignancy, and its molecular basis is poorly understood. We previously
      demonstrated that opioid binding protein cell adhesion molecule (OPCML) was
      frequently epigenetically inactivated in epithelial ovarian cancers, with tumor
      suppressor function in vitro and in vivo. Here, we further show the clinical
      relevance of OPCML and demonstrate that OPCML functions by a novel mechanism in
      epithelial ovarian cancer cell lines and normal ovarian surface epithelial cells
      by regulating a specific repertoire of receptor tyrosine kinases: EPHA2, FGFR1,
      FGFR3, HER2, and HER4. OPCML negatively regulates receptor tyrosine kinases by
      binding their extracellular domains, altering trafficking via nonclathrin
      dependent endocytosis, and promoting their degradation via a polyubiquitination
      associated proteasomal mechanism leading to signaling and growth inhibition.
      Exogenous recombinant OPCML domain 1-3 protein inhibited the cell growth of
      epithelial ovarian cancers cell in vitro and in vivo in 2 murine ovarian cancer
      intraperitoneal models that used an identical mechanism. These findings
      demonstrate a novel mechanism of OPCML-mediated tumor suppression and provide a
      proof-of-concept for recombinant OPCML protein therapy in epithelial ovarian
      cancers. SIGNIFICANCE: The OPCML tumor suppressor negatively regulates a specific
      spectrum of receptor tyrosine kinases in ovarian cancer cells by binding to their
      extracellular domain and altering trafficking to a nonclathrin, caveolin-1
      associated endosomal pathway that results in receptor tyrosine kinase
      polyubiquitination and proteasomal degradation. Recombinant OPCML domain 1-3
      recapitulates this mechanism and may allow for the implementation of an
      extracellular tumor-suppressor replacement strategy.

PMID- 22585865
TI  - Antiestrogen drugs might prevent lung cancer.
AB  - Mice exposed to tobacco carcinogens developed fewer tumors when exposed to agents
      that block the effect of estrogen.

PMID- 22585863
TI  - Immune cells may promote skin cancer.
AB  - In mice, Langerhans cells may absorb a toxic chemical and metabolize it into a
      substance even more toxic to surrounding cells.

PMID- 22585861
TI  - Essential gene profiles in breast, pancreatic, and ovarian cancer cells.
AB  - Genomic analyses are yielding a host of new information on the multiple genetic
      abnormalities associated with specific types of cancer. A comprehensive
      description of cancer-associated genetic abnormalities can improve our ability to
      classify tumors into clinically relevant subgroups and, on occasion, identify
      mutant genes that drive the cancer phenotype ("drivers"). More often, though, the
      functional significance of cancer-associated mutations is difficult to discern.
      Genome-wide pooled short hairpin RNA (shRNA) screens enable global identification
      of the genes essential for cancer cell survival and proliferation, providing a
      "functional genomic" map of human cancer to complement genomic studies. Using a
      lentiviral shRNA library targeting ~16,000 genes and a newly developed, dynamic
      scoring approach, we identified essential gene profiles in 72 breast, pancreatic,
      and ovarian cancer cell lines. Integrating our results with current and future
      genomic data should facilitate the systematic identification of drivers,
      unanticipated synthetic lethal relationships, and functional vulnerabilities of
      these tumor types. SIGNIFICANCE: This study presents a resource of genome-scale,
      pooled shRNA screens for 72 breast, pancreatic, and ovarian cancer cell lines
      that will serve as a functional complement to genomics data, facilitate
      construction of essential gene profiles, help uncover synthetic lethal
      relationships, and identify uncharacterized genetic vulnerabilities in these
      tumor types. SIGNIFICANCE: This study presents a resource of genome-scale, pooled
      shRNA screens for 72 breast, pancreatic, and ovarian cancer cell lines that will
      serve as a functional complement to genomics data, facilitate construction of
      essential gene profiles, help uncover synthetic lethal relationships, and
      identify uncharacterized genetic vulnerabilities in these tumor types.

PMID- 22585866
TI  - NCATS is out of the bag.
AB  - NIH has officially launched the National Center for Advancing Translational
      Sciences, a "hub for catalyzing innovations in translational science."

PMID- 22585864
TI  - Web applications aid clinical trial recruitment.
AB  - The websites Ask Dory and My Cancer Genome won a government-sponsored contest for
      providing details on clinical trials and genetic mutations for cancer patients,
      clinicians, and researchers.

PMID- 22585867
TI  - Putting tumors to the blood test.
AB  - Detection devices that combine advances in biology, nanotechnology, and
      microfluidics are dramatically broadening the sensitivity and scope of "liquid
      biopsies" for cancer research, detection, and treatment.

PMID- 22585868
TI  - Gene inactivation promotes immune escape in DLBCL.
AB  - Major finding: The majority of DLBCLs fail to express cell surface-associated B2M
      and CD58. CONCEPT: DLBCLs evade immune recognition by both CTLs and NK cells.
      IMPACT: Immune escape provides selective pressure during lymphomagenesis.

PMID- 22585869
TI  - ROS1 gene rearrangement is identified in NSCLC.
AB  - MAJOR FINDING: ROS1 chromosomal rearrangements define a molecular subtype of
      NSCLC. IMPACT: ROS1 rearrangements tend to occur in younger, non-smoking NSCLC
      patients. CLINICAL RELEVANCE: ROS1-positive NSCLC patients may benefit from
      crizotinib therapy.

PMID- 22585870
TI  - Effects of a culturally grounded community-based diabetes prevention program for
      obese Latino adolescents.
AB  - PURPOSE: The purpose of this study was to test the feasibility and preliminary
      effects of a culturally grounded, community-based diabetes prevention program
      among obese Latino adolescents. METHODS: Fifteen obese Latino adolescents (body
      mass index [BMI] percentile = 96.3 +/- 1.1, age = 15.0 +/- 0.9 years) completed a
      12-week intervention that included weekly lifestyle education classes delivered
      by bilingual/bicultural promotoras and three, 60-minute physical activity
      sessions per week. Participants were assessed for anthropometrics (height,
      weight, BMI, and waist circumference), cardiorespiratory fitness, physical
      activity/inactivity, nutrition behaviors, and insulin sensitivity and glucose
      tolerance by a 2-hour oral glucose tolerance test. RESULTS: The intervention
      resulted in significant decreases in BMI z score, BMI percentile, and waist
      circumference; increases in cardiorespiratory fitness; and decreases in physical
      inactivity and dietary fat consumption. In addition to these changes, the
      intervention led to significant improvements in insulin sensitivity and
      reductions in 2-hour glucose levels. CONCLUSIONS: These results support the
      feasibility and efficacy of a community-based diabetes prevention program for
      high-risk Latino youth. Translational approaches that are both culturally
      grounded and biologically meaningful represent a novel and innovative strategy
      for closing the obesity-related health disparities gap.

PMID- 22585871
TI  - Comorbid diabetes and eating disorders in adult patients: assessment and
      considerations for treatment.
AB  - PURPOSE: The lack of research concerning treatment for individuals with diabetes
      mellitus (DM) and comorbid eating disorders (ED) contributes to the gulf between
      the psychosocial needs of individuals with the two conditions and the treatment
      they receive. Empirical evidence has established that the prognosis of patients
      with this comorbid diagnosis (ED-DM) is poor in the absence of a specialized DM
      treatment specifically adapted to ED. In individuals with DM, comorbid ED is
      associated with numerous complications. Despite these interactions, current
      knowledge about the comorbid diagnosis is limited, and eating disorders in
      patients with diabetes often remain undiagnosed. This article presents standard
      procedures for assessment and optimal therapeutic interventions for patients with
      ED and DM. CONCLUSION: In patients with diabetes, problematic eating behaviors
      and symptoms should be assessed routinely. When an eating disorder is detected,
      diabetes management needs to be adapted, binge eating or medication misuse needs
      to be addressed, and eating disorder specialists should be included in the
      multidisciplinary team.

PMID- 22585872
TI  - Highlight--tracking adaptation's role: do larger populations evolve faster?

PMID- 22585873
TI  - Copy number variation detection and genotyping from exome sequence data.
AB  - While exome sequencing is readily amenable to single-nucleotide variant
      discovery, the sparse and nonuniform nature of the exome capture reaction has
      hindered exome-based detection and characterization of genic copy number
      variation. We developed a novel method using singular value decomposition (SVD)
      normalization to discover rare genic copy number variants (CNVs) as well as
      genotype copy number polymorphic (CNP) loci with high sensitivity and specificity
      from exome sequencing data. We estimate the precision of our algorithm using 122
      trios (366 exomes) and show that this method can be used to reliably predict (94%
      overall precision) both de novo and inherited rare CNVs involving three or more
      consecutive exons. We demonstrate that exome-based genotyping of CNPs strongly
      correlates with whole-genome data (median r(2) = 0.91), especially for loci with
      fewer than eight copies, and can estimate the absolute copy number of multi
      allelic genes with high accuracy (78% call level). The resulting user-friendly
      computational pipeline, CoNIFER (copy number inference from exome reads), can
      reliably be used to discover disruptive genic CNVs missed by standard approaches
      and should have broad application in human genetic studies of disease.

PMID- 22585874
TI  - Political economy analysis for tobacco control in low- and middle-income
      countries.
AB  - Tobacco is already the world's leading cause of preventable death, claiming over
      5 million lives annually, and this toll is rising. Even though effective tobacco
      control policies are well researched and widely disseminated, they remain largely
      unimplemented in most low- and middle-income countries (LMICs). For the most
      part, control attempts by advocates and government regulators have been
      frustrated by transnational tobacco companies (TTCs) and their supporters. One
      reason tobacco is so difficult to control is that its political economy has yet
      to be adequately understood and addressed. We conducted a review of the
      literature on tobacco control in LMICs using the databases PubMed, EconLit,
      PsychInfo and AGRICOLA. Among the over 2500 papers and reports we identified,
      very few explicitly applied political economy analysis to tobacco control in an
      LMIC setting. The vast majority of papers characterized important aspects of the
      tobacco epidemic, including who smokes, the effects of smoking on health, the
      effectiveness of advertising bans, and the activities of TTCs and their allies.
      But the political and economic dynamics of policy adoption and implementation
      were not discussed in any but a handful of papers. To help control advocates
      better understand and manage the process of policy implementation, we identify
      how political economy analysis would differ from the traditional public health
      approaches that dominate the literature. We focus on five important problem
      areas: information problems and the risks of smoking; the roles of domestic
      producers; multinational corporations and trade disputes in consumption;
      smuggling; the barriers to raising taxes and establishing spatial restrictions on
      smoking; and incentive conflicts between government branches. We conclude by
      discussing the political economy of tobacco and its implications for control
      strategies.

PMID- 22585876
TI  - Power of partnership is the theme of the 2012 AADE Annual Meeting.

PMID- 22585881
TI  - Intranasal steroids for acute sinusitis?

PMID- 22585882
TI  - What does it cost to change behavior?

PMID- 22585883
TI  - Health coaching to improve hypertension treatment in a low-income, minority
      population.
AB  - PURPOSE: Poor blood pressure control is common in the United States. We conducted
      a study to determine whether health coaching with home titration of
      antihypertensive medications can improve blood pressure control compared with
      health coaching alone in a low-income, predominantly minority population.
      METHODS: We randomized 237 patients with poorly controlled hypertension at a
      primary care clinic to receive either home blood pressure monitoring, weekly
      health coaching, and home titration of blood pressure medications if blood
      pressures were elevated (n = 129) vs home blood pressure monitoring and health
      coaching but no home titration (n = 108). The primary outcome was change in
      systolic blood pressure from baseline to 6 months. RESULTS: Both the home
      titration arm and the no-home-titration arm had a reduction in systolic blood
      pressure, with no significant difference between them. When both arms were
      combined and analyzed as a before-after study, there was a mean decrease in
      systolic blood pressure of 21.8 mm Hg (P <.001) as well as a decrease in the
      number of primary care visits from 3.5 in the 6 months before the study to 2.6
      during the 6-month study period (P <.001) and 2.4 in the 6 months after the study
      (P <.001). The more coaching encounters patients had, the greater their reduction
      in blood pressure. CONCLUSIONS: Blood pressure control in a low-income, minority
      population can be improved by teaching patients to monitor their blood pressure
      at home and having nonprofessional health coaches assist patients, in particular,
      by counseling them on medication adherence. The improved blood pressure control
      can be achieved while reducing the time spent by physicians.

PMID- 22585884
TI  - Healthy Steps trial: pedometer-based advice and physical activity for low-active
      older adults.
AB  - PURPOSE: We compared the effectiveness of 2 physical activity prescriptions
      delivered in primary care--the standard time-based Green Prescription and a
      pedometer step-based Green Prescription--on physical activity, body mass index
      (BMI), blood pressure, and quality of life in low-active older adults. METHODS:
      We undertook a randomized controlled trial involving 330 low-active older adults
      (aged =65 years) recruited through their primary care physicians' patient
      databases. Participants were randomized to either the pedometer step-based Green
      Prescription group (n = 165) or the standard Green Prescription group (n = 165).
      Both groups had a visit with the primary care practitioner and 3 telephone
      counseling sessions over 12 weeks aimed at increasing physical activity. Outcomes
      were the changes in physical activity (assessed with the Auckland Heart Study
      Physical Activity Questionnaire), blood pressure, BMI, quality of life (assessed
      with the 36-Item Short Form Health Survey), physical function status (assessed
      with the Short Physical Performance Battery), and falls over a 12-month period.
      RESULTS: Of the patients invited to participate, 57% responded. At 12 months,
      leisure walking increased by 49.6 min/wk for the pedometer Green Prescription
      compared with 28.1 min/wk for the standard Green Prescription (P=.03). For both
      groups, there were significant increases across all physical activity domains at
      3 months (end of intervention) that were largely maintained after 12 months of
      follow-up. BMI did not change in either group. Significant improvements in blood
      pressure were observed for both groups without any differences between them.
      CONCLUSIONS: Pedometer use resulted in a greater increase in leisure walking
      without any impact on overall activity level. All participants increased physical
      activity, and on average, their blood pressure decreased over 12 months, although
      the clinical relevance is unknown.

PMID- 22585885
TI  - Involving the health care system in domestic violence: what women want.
AB  - PURPOSE Domestic violence is prevalent among women using primary health care
      services in Lebanon and has a negative effect on their health, yet physicians are
      not inquiring about it. In this study, we explored the attitudes of these women
      regarding involving the health care system in domestic violence management. 
      METHODS We undertook a qualitative focus group study. Health care professionals
      in 6 primary health care centers routinely screened women for domestic violence
      using the HITS (Hurt, Insult, Threaten, Scream) instrument. At each center, 12
      women who were screened (regardless of the result) were recruited to participate
      in a focus group discussion.  RESULTS Most of the 72 women encouraged involvement
      of the health care system in the management of domestic violence and considered
      it to be a "socially accepted way to break the silence." Women expected health
      care professionals to have an "active conscience"; to be open minded, ready to
      listen, and unhurried; and to respect confidentiality. Additionally, they
      recommended mass media and community awareness campaigns focusing on family
      relationships to address domestic violence.  CONCLUSIONS Addressing domestic
      violence through the health care system, if done properly, may be socially
      acceptable and nonoffensive even to women living in conservative societies such
      as Lebanon. The women in this study described characteristics of health
      professionals that would be conducive to screening and that could be extrapolated
      to the health care of immigrant Arab women.

PMID- 22585886
TI  - Typical electronic health record use in primary care practices and the quality of
      diabetes care.
AB  - PURPOSE: Recent efforts to encourage meaningful use of electronic health records
      (EHRs) assume that widespread adoption will improve the quality of ambulatory
      care, especially for complex clinical conditions such as diabetes. Cross
      sectional studies of typical uses of commercially available ambulatory EHRs
      provide conflicting evidence for an association between EHR use and improved
      care, and effects of longer-term EHR use in community-based primary care settings
      on the quality of care are not well understood. METHODS: We analyzed data from 16
      EHR-using and 26 non-EHR-using practices in 2 northeastern states participating
      in a group-randomized quality improvement trial. Measures of care were assessed
      for 798 patients with diabetes. We used hierarchical linear models to examine the
      relationship between EHR use and adherence to evidence-based diabetes care
      guidelines, and hierarchical logistic models to compare rates of improvement over
      3 years. RESULTS: EHR use was not associated with better adherence to care
      guidelines or a more rapid improvement in adherence. In fact, patients in
      practices that did not use an EHR were more likely than those in practices that
      used an EHR to meet all of 3 intermediate outcomes targets for hemoglobin A(1c),
      low-density lipoprotein cholesterol, and blood pressure at the 2-year follow-up
      (odds ratio = 1.67; 95% CI, 1.12-2.51). Although the quality of care improved
      across all practices, rates of improvement did not differ between the 2 groups.
      CONCLUSIONS: Consistent use of an EHR over 3 years does not ensure successful use
      for improving the quality of diabetes care. Ongoing efforts to encourage adoption
      and meaningful use of EHRs in primary care should focus on ensuring that use
      succeeds in improving care. These efforts will need to include provision of
      assistance to longer-term EHR users.

PMID- 22585887
TI  - Effect of a UK pay-for-performance program on ethnic disparities in diabetes
      outcomes: interrupted time series analysis.
AB  - PURPOSE: We wanted to examine the long-term effects of the Quality and Outcomes
      Framework (QOF), a major pay-for-performance program in the United Kingdom, on
      ethnic disparities in diabetes outcomes. METHODS: We undertook an interrupted
      time series analysis of electronic medical record data of diabetes patients
      registered with 29 family practices in South West London, United Kingdom. Main
      outcome measures were mean hemoglobin A(1c) (HbA(1c)), total cholesterol, and
      blood pressure. RESULTS: The introduction of QOF was associated with initial
      accelerated improvements in systolic blood pressure in white and black patients,
      but these improvements were sustained only in black patients (annual decrease: 
      1.68 mm Hg; 95% CI, -2.41 to -0.95 mm Hg). Initial improvements in diastolic
      blood pressure in white patients (-1.01 mm Hg; 95% CI, -1.79 to -0.24 mm Hg) and
      in cholesterol in white (-0.13 mmol/L; 95% CI, -0.21 to -0.05 mmol/L) and black (
      0.10 mmol/L; 95% CI, -0.20 to -0.01 mmol/L) patients were not sustained in the
      post-QOF period. There was no beneficial impact of QOF on HbA(1c) in any ethnic
      group. Existing disparities in risk factor control remained largely intact (for
      example; mean HbA(1c): white 7.5%, black 7.8%, south Asian 7.8%; P <.05) at the
      end of the study period. CONCLUSION: A universal pay-for-performance scheme did
      not appear to address important disparities in chronic disease management over
      time. Targeted quality improvement strategies may be required to improve health
      care in vulnerable populations.

PMID- 22585888
TI  - Intraclass correlation coefficients typical of cluster-randomized studies:
      estimates from the Robert Wood Johnson Prescription for Health projects.
AB  - PURPOSE: Researchers who conduct cluster-randomized studies must account for
      clustering during study planning; failure to do so can result in insufficient
      study power. To plan adequately, investigators need accurate estimates of
      clustering in the form of intraclass correlation coefficients (ICCs). METHODS: We
      used data for 5,042 patients, from 61 practices in 8 practice-based research
      networks, obtained from the Prescription for Health program, sponsored by the
      Robert Wood Johnson Fund, to estimate ICCs for demographic and behavioral
      variables and for physician and practice characteristics. We used an approach
      similar to analysis of variance to calculate ICCs for binary variables and mixed
      models that directly estimated between- and within-cluster variances to calculate
      ICCs for continuous variables. RESULTS: ICCs indicating substantial within
      practice clustering were calculated for age (ICC = 0.151), race (ICC = 0.265),
      and such behaviors as smoking (ICC = 0.118) and unhealthy diet (ICC = 0.206).
      Patients' intent-to-change behaviors related to smoking, diet, or exercise were
      less clustered (ICCs <=0.007). Within-network ICCs were generally smaller,
      reflecting heterogeneity among practices within the same network. ICCs for
      practice-level measures indicated that practices within networks were relatively
      homogenous with respect to practice type (ICC = 0.29) and the use of electronic
      medical records (ICC = 0.23), but less homogenous with respect to size and rates
      of physician and staff turnover. CONCLUSION: ICCs for patient behaviors and
      intent to change those behaviors were generally less than 0.1. Though small, such
      ICCs are not trivial; if cluster sizes are large, even small levels of clustering
      that is unaccounted for reduces the statistical power of a cluster-randomized
      study.

PMID- 22585889
TI  - Intranasal corticosteroids in management of acute sinusitis: a systematic review
      and meta-analysis.
AB  - PURPOSE: Acute sinusitis is a common condition in ambulatory care, where it is
      frequently treated with antibiotics, despite little evidence of their benefit.
      Intranasal corticosteroids might relieve symptoms; however, evidence for this
      benefit is currently unclear. We performed a systematic review and meta-analysis
      of the effects of intranasal corticosteroids on the symptoms of acute sinusitis.
      METHODS: We searched MEDLINE, EMBASE, the Cochrane Central register of Controlled
      Trials (CENTRAL), and Centre for Reviews and Dissemination databases until
      February 2011 for studies comparing intranasal corticosteroids with placebo in
      children or adults having clinical symptoms and signs of acute sinusitis or
      rhinosinusitis in ambulatory settings. We excluded chronic/allergic sinusitis.
      Two authors independently extracted data and assessed the studies' methodologic
      quality. RESULTS: We included 6 studies having a total of 2,495 patients. In 5
      studies, antibiotics were prescribed in addition to corticosteroids or placebo.
      Intranasal corticosteroids resulted in a significant, small increase in
      resolution of or improvement in symptoms at days 14 to 21 (risk difference [RD] =
      0.08; 95% CI, 0.03-0.13). Analysis of individual symptom scores revealed most
      consistently significant benefits for facial pain and congestion. Subgroup
      analysis by time of reported outcomes showed a significant beneficial effect at
      21 days (RD = 0.11; 95% CI, 0.06-0.17), but not at 14 to 15 days (RD = 0.05; 95%
      CI, -0.01 to 0.11). Meta-regression analysis of trials using different doses of
      mometasone furoate showed a significant dose-response relationship (P=.02).
      CONCLUSIONS: Intranasal corticosteroids offer a small therapeutic benefit in
      acute sinusitis, which may be greater with high doses and with courses of 21
      days' duration. Further trials are needed in antibiotic-naive patients.

PMID- 22585890
TI  - Communities of solution: the Folsom Report revisited.
AB  - Efforts to address the current fragmented US health care structure, including
      controversial federal reform, cannot succeed without a reinvigoration of
      community-centered health systems. A blueprint for systematic implementation of
      community services exists in the 1967 Folsom Report--calling for "communities of
      solution." We propose an updated vision of the Folsom Report for integrated and
      effective services, incorporating the principles of community-oriented primary
      care. The 21st century primary care physician must be a true public health
      professional, forming partnerships and assisting data sharing with community
      organizations to facilitate healthy changes. Current policy reform efforts should
      build upon Folsom Report's goal of transforming personal and population health.

PMID- 22585891
TI  - Rewarding healthy behaviors--pay patients for performance.
AB  - Despite a considerable investment of resources into pay for performance,
      preliminary studies have found that it may not be significantly more effective in
      improving health outcome measures when compared with voluntary quality
      improvement programs. Because patient behaviors ultimately affect health
      outcomes, I would propose a novel pay-for-performance program that rewards
      patients directly for achieving evidence-based health goals. These rewards would
      be in the form of discounts towards co-payments for doctor's visits, procedures,
      and medications, thereby potentially reducing cost and compliance issues. A pilot
      study recruiting patients with diabetes or hypertension, diseases with clear and
      objective outcome measures, would be useful to examine true costs, savings, and
      health outcomes of such a reward program. Offering incentives to patients for
      reaching health goals has the potential to foster a stronger partnership between
      doctors and patients and improve health outcomes.

PMID- 22585892
TI  - The joy of family practice.
AB  - Many family physicians have written about how they influence, nurture, and
      empower people in their communities of practice. In this essay, the author writes
      of the personal joys that family medicine has brought him. An expression of his
      appreciation for his work as a family doctor, it touches on 6 themes that
      continue to rejuvenate his practice: love, faith, mystery, place, dance, and
      medicine. By examining the emotional and psychological dimensions of these
      themes, he offers a path by which other family physicians may be able to find
      sustenance and joy in their daily work.

PMID- 22585893
TI  - Why ADFM moved the 2013 Annual Winter Meeting.

PMID- 22585894
TI  - Education gaps between family physicians and licensed nurse practitioners.

PMID- 22585896
TI  - Family medicine match rate increases slightly.

PMID- 22585897
TI  - Cheating: its implications for ABFM examinees.

PMID- 22585898
TI  - STFM unveils the National Family Medicine Clerkship Curriculum website.

PMID- 22585900
TI  - (N-3) Fatty acids: molecular role and clinical uses in psychiatric disorders.
AB  - New discoveries in the field of neurophysiology and neuropharmacology have
      revealed the role of (n-3) fatty acids in controlling inflammation and protecting
      neuron cells from oxidative damage, preserving their function. It has also been
      thought that their psychoactive properties could be beneficial in certain
      psychiatric illnesses. This article discusses the newest discoveries of the
      affected activities by these fats in the cerebral cortex and the efforts that
      have been made to put them in practice in clinical trials in humans. In general,
      we were able to detect certain discord in the scientific community when designing
      placebo-based studies (mainly in establishing the appropriate therapeutic dose of
      (n-3) fatty acids, varying from the recommended dietary dose to an amount that
      may be 3 or 4 times higher), and in interpreting results. Although many studies
      have had the validity of their results questioned because of their small sample
      size, several studies seem to indicate that the (n-3) fatty acids are useful
      therapeutic tools in treating psychiatric conditions such as major depression,
      bipolar disorder, and several other disorders. Larger sample size studies are
      still required to better analyze the treatment potential of these agents.

PMID- 22585901
TI  - Influence of dairy product and milk fat consumption on cardiovascular disease
      risk: a review of the evidence.
AB  - Although evidence has linked the consumption of saturated fat (SF) to increased
      LDL levels and an increased risk of the development of cardiovascular disease
      (CVD), recent findings have indicated that the link between CVD and SF may be
      less straightforward than originally thought. This may be due to the fact that
      some food sources high in SF contain an array of saturated and unsaturated fatty
      acids, each of which may differentially affect lipoprotein metabolism, as well as
      contribute significant amounts of other nutrients, which may alter CVD risk. The
      purpose of this review is to examine the published research on the relationship
      between milk fat containing dairy foods and cardiovascular health. The findings
      indicate that the majority of observational studies have failed to find an
      association between the intake of dairy products and increased risk of CVD,
      coronary heart disease, and stroke, regardless of milk fat levels. Results from
      short-term intervention studies on CVD biomarkers have indicated that a diet
      higher in SF from whole milk and butter increases LDL cholesterol when
      substituted for carbohydrates or unsaturated fatty acids; however, they may also
      increase HDL and therefore might not affect or even lower the total
      cholesterol:HDL cholesterol ratio. The results from the review also indicate that
      cheese intake lowers LDL cholesterol compared with butter of equal milk fat
      content. In addition, the review highlights some significant gaps in the research
      surrounding the effects of full-fat dairy on CVD outcomes, pointing to the need
      for long-term intervention studies.

PMID- 22585902
TI  - Regulation of hepatic glucose uptake and storage in vivo.
AB  - In the postprandial state, the liver takes up and stores glucose to minimize the
      fluctuation of glycemia. Elevated insulin concentrations, an increase in the load
      of glucose reaching the liver, and the oral/enteral/portal vein route of glucose
      delivery (compared with the peripheral intravenous route) are factors that
      increase the rate of net hepatic glucose uptake (NHGU). The entry of glucose into
      the portal vein stimulates a portal glucose signal that not only enhances NHGU
      but concomitantly reduces muscle glucose uptake to ensure appropriate
      partitioning of a glucose load. This coordinated regulation of glucose uptake is
      likely neurally mediated, at least in part, because it is not observed after
      total hepatic denervation. Moreover, there is evidence that both the sympathetic
      and the nitrergic innervation of the liver exert a tonic repression of NHGU that
      is relieved under feeding conditions. Further, the energy sensor 5'AMP-activated
      protein kinase appears to be involved in regulation of NHGU and glycogen storage.
      Consumption of a high-fat and high-fructose diet impairs NHGU and glycogen
      storage in association with a reduction in glucokinase protein and activity. An
      understanding of the impact of nutrients themselves and the route of nutrient
      delivery on liver carbohydrate metabolism is fundamental to the development of
      therapies for impaired postprandial glucoregulation.

PMID- 22585903
TI  - The transcription factor network associated with the amino acid response in
      mammalian cells.
AB  - Mammals exhibit multiple adaptive mechanisms that sense and respond to
      fluctuations in dietary nutrients. Consumption of reduced total dietary protein
      or a protein diet that is deficient in 1 or more of the essential amino acids
      triggers wide-ranging changes in feeding behavior and gene expression. At the
      level of individual cells, dietary protein deficiency is manifested as amino acid
      (AA) deprivation, which activates the AA response (AAR). The AAR is composed of a
      collection of signal transduction pathways that terminate in specific
      transcriptional programs designed to catalyze adaptation to the nutrient stress
      or, ultimately, undergo apoptosis. Independently of the AAR, endoplasmic
      reticulum stress activates 3 signaling pathways, collectively referred to as the
      unfolded protein response. The transcription factor activating transcription
      factor 4 is one of the terminal transcriptional mediators for both the AAR and
      the unfolded protein response, leading to a significant degree of overlap with
      regard to the target genes for these stress pathways. Over the past 5 y, research
      has revealed that the basic leucine zipper superfamily of transcription factors
      plays the central role in the AAR. Formation of both homo- and heterodimers among
      the activating transcription factor, CCAAT enhancer-binding protein, and FOS/JUN
      families of basic leucine zipper proteins forms the nucleus of a highly
      integrated transcription factor network that determines the initiation,
      magnitude, and duration of the cellular response to dietary protein or AA
      limitation.

PMID- 22585906
TI  - Vitamin E.

PMID- 22585907
TI  - Institute of Medicine. 2012. Front-of-Package Nutrition Rating Systems and
      Symbols: Promoting Healthier Choices. Washington, DC: The National Academies
      Press.

PMID- 22585905
TI  - Brain responses to high-protein diets.
AB  - Proteins are suspected to have a greater satiating effect than the other 2
      macronutrients. After protein consumption, peptide hormones released from the
      gastrointestinal tract (mainly anorexigenic gut peptides such as cholecystokinin,
      glucagon peptide 1, and peptide YY) communicate information about the energy
      status to the brain. These hormones and vagal afferents control food intake by
      acting on brain regions involved in energy homeostasis such as the brainstem and
      the hypothalamus. In fact, a high-protein diet leads to greater activation than a
      normal-protein diet in the nucleus tractus solitarius and in the arcuate nucleus.
      More specifically, neural mechanisms triggered particularly by leucine
      consumption involve 2 cellular energy sensors: the mammalian target of rapamycin
      and AMP-activated protein kinase. In addition, reward and motivation aspects of
      eating behavior, controlled mainly by neurons present in limbic regions, play an
      important role in the reduced hedonic response of a high-protein diet. This
      review examines how metabolic signals emanating from the gastrointestinal tract
      after protein ingestion target the brain to control feeding, energy expenditure,
      and hormones. Understanding the functional roles of brain areas involved in the
      satiating effect of proteins and their interactions will demonstrate how
      homeostasis and reward are integrated with the signals from peripheral organs
      after protein consumption.

PMID- 22585908
TI  - Institutional policy change to promote health and sustainability through food.

PMID- 22585909
TI  - Developing and implementing health and sustainability guidelines for
      institutional food service.
AB  - Health and sustainability guidelines for institutional food service are directed
      at improving dietary intake and increasing the ecological benefits of the food
      system. The development and implementation of institutional food service
      guidelines, such as the Health and Human Services (HHS) and General Services
      Administration (GSA) Health and Sustainability Guidelines for Federal Concessions
      and Vending Operations (HHS/GSA Guidelines), have the potential to improve the
      health and sustainability of the food system. Institutional guidelines assist
      staff, managers, and vendors in aligning the food environment at food service
      venues with healthier and more sustainable choices and practices. Guideline
      specifics and their effective implementation depend on the size, culture, nature,
      and management structure of an institution and the individuals affected. They may
      be applied anywhere food is sold, served, or consumed. Changing institutional
      food service practice requires comprehensive analysis, engagement, and education
      of all relevant stakeholders including institutional management, members of the
      food supply chain, and customers. Current examples of food service guidelines
      presented here are the HHS and GSA Health and Sustainability Guidelines for
      Federal Concessions and Vending Operations, which translate evidence-based
      recommendations on health and sustainability into institutional food service
      practices and are currently being implemented at the federal level. Developing
      and implementing guidelines has the potential to improve long-term population
      health outcomes while simultaneously benefitting the food system. Nutritionists,
      public health practitioners, and researchers should consider working with
      institutions to develop, implement, and evaluate food service guidelines for
      health and sustainability.

PMID- 22585904
TI  - Eukaryotic initiation factor 2 phosphorylation and translational control in
      metabolism.
AB  - Regulation of mRNA translation is a rapid and effective means to couple changes
      in the cellular environment with global rates of protein synthesis. In response
      to stresses, such as nutrient deprivation and accumulation of misfolded proteins
      in the endoplasmic reticulum, phosphorylation of the alpha subunit of eukaryotic
      initiation factor 2 (eIF2alpha~P) reduces general translation initiation while
      facilitating the preferential translation of select transcripts, such as that
      encoding activating transcription factor 4 (ATF4), a transcriptional activator of
      genes subject to the integrated stress response (ISR). In this review, we
      highlight the translational control processes regulated by nutritional stress,
      with an emphasis on the events triggered by eIF2alpha~P, and describe the family
      of eukaryotic initiation factor 2 kinases and the mechanisms by which each sense
      different stresses. We then address 3 questions. First, what are the mechanisms
      by which eIF2alpha~P confers preferential translation on select mRNA and what are
      the consequences of the gene expression induced by the ISR? Second, what are the
      molecular processes by which certain stresses can differentially activate
      eIF2alpha~P and ATF4 expression? The third question we address is what are the
      modes of cross-regulation between the ISR and other stress response pathways,
      such as the unfolded protein response and mammalian target of rapamycin, and how
      do these regulatory schemes provide for gene expression programs that are
      tailored for specific stresses? This review highlights recent advances in each of
      these areas of research, emphasizing how eIF2alpha~P and the ISR can affect
      metabolic health and disease.

PMID- 22585910
TI  - Farm to institution: creating access to healthy local and regional foods.
AB  - Farm to Institution (FTI) programs are one approach to align food service
      operations with health and sustainability guidelines, such as those recently
      developed by the U.S. Department of Health and Human Services and General
      Services Administration. Programs and policies that support sourcing local and
      regional foods for schools, hospitals, faith-based organizations, and worksites
      may benefit institutional customers and their families, farmers, the local
      community, and the economy. Different models of FTI programs exist. On-site
      farmer's markets at institutions have been promoted on federal government
      property, healthcare facilities, and private institutions nationwide. Farm to
      School programs focus on connecting schools with local agricultural production
      with the goal of improving school meals and increasing intake of fruits and
      vegetables in children. Sourcing food from local farms presents a number of
      challenges including cost and availability of local products, food safety, and
      liability considerations and lack of skilled labor for food preparation.
      Institutions utilize multiple strategies to address these barriers, and local,
      state, and federal polices can help facilitate FTI approaches. FTI enables the
      purchasing power of institutions to contribute to regional and local food
      systems, thus potentially affecting social, economic, and ecological systems.
      Local and state food policy councils can assist in bringing stakeholders together
      to inform this process. Rigorous research and evaluation is needed to determine
      and document best practices and substantiate links between FTI and multiple
      outcomes. Nutritionists, public health practitioners, and researchers can help
      communities work with institutions to develop, implement, and evaluate programs
      and policies supporting FTI.

PMID- 22585911
TI  - Impact of maternal nutritional status on human milk quality and infant outcomes:
      an update on key nutrients.

PMID- 22585912
TI  - Maternal vitamin D status: effect on milk vitamin D content and vitamin D status
      of breastfeeding infants.
AB  - There are increasing reports of rickets and vitamin D deficiency worldwide.
      Breastfeeding without adequate sunlight exposure and vitamin D supplementation
      are the major risk factors. In view of the drive to promote and increase the rate
      of exclusive breastfeeding, the relationship among maternal vitamin D status,
      vitamin D concentration of human milk, and hence vitamin D status of
      breastfeeding infants deserves reassessment. This review provides current
      information on the interrelationship between maternal vitamin D status and the
      vitamin D status of the breastfeeding infant. It also reviews the results of
      ongoing research on the effect of high-dose maternal vitamin D supplementation
      alone as a possible option to prevent vitamin D deficiency in the breastfeeding
      mother-infant dyad.

PMID- 22585913
TI  - B vitamins in breast milk: relative importance of maternal status and intake, and
      effects on infant status and function.
AB  - Infants should be exclusively breastfed for the first 6 mo of life. However,
      maternal deficiency of some micronutrients, conveniently classified as Group I
      micronutrients during lactation, can result in low concentrations in breast milk
      and subsequent infant deficiency preventable by improving maternal status. This
      article uses thiamin, riboflavin, vitamin B-6, vitamin B-12, and choline as
      examples and reviews the evidence for risk of inadequate intakes by infants in
      the first 6 mo of life. Folate, a Group II micronutrient, is included for
      comparison. Information is presented on forms and concentrations in human milk,
      analytical methods, the basis of current recommended intakes for infants and
      lactating women, and effects of maternal supplementation. From reports of
      maternal and/or infant deficiency, concentrations in milk were noted as well as
      any consequences for infant function. These milk values were used to estimate the
      percent of recommended daily intake that infants fed by a deficient mother could
      obtain from her milk. Estimates were 60% for thiamin, 53% for riboflavin, 80% for
      vitamin B-6, 16% for vitamin B-12, and 56% for choline. Lack of data limits the
      accuracy and generalizability of these conclusions, but the overall picture that
      emerges is consistent across nutrients and points to an urgent need to improve
      the information available on breast milk quality.

PMID- 22585915
TI  - Introduction to the symposium.

PMID- 22585914
TI  - Maternal dietary DHA supplementation to improve inflammatory outcomes in the
      preterm infant.
AB  - Dietary DHA (22:6n-3) is a long-chain PUFA that has provocative effects on
      inflammatory signal events that could potentially affect preterm infant health.
      It is well known that the essential fatty acid of the (n-3) series; alpha
      linolenic acid (18:3n:3) can be desaturated and elongated in the liver
      endoplasmic reticulum and peroxisome to produce the 22-carbon DHA. Nevertheless,
      concern exists as to the efficiency of this mechanism in providing the preterm
      infant with adequate DHA. Activity of the delta-6-desaturase and the delta-5
      desaturase necessary for DHA synthesis is decreased by protein deprivation. The
      combined effects of suboptimal intake of both DHA and protein in the preterm
      infants could have substantial clinical consequences.

PMID- 22585916
TI  - Structure-function relationships of human milk oligosaccharides.
AB  - Human milk contains more than a hundred structurally distinct oligosaccharides.
      In this review, we provide examples of how the structural characteristics of
      these human milk oligosaccharides (HMO) determine functionality. Specific alpha1
      2-fucosylated HMO have been shown to serve as antiadhesive antimicrobials to
      protect the breast-fed infant against infections with Campylobacter jejuni, one
      of the most common causes of bacterial diarrhea. In contrast, alpha1-2
      fucosylation may abolish the beneficial effects of HMO against Entamoeba
      histolytica, a protozoan parasite that causes colitis, acute dysentery, or
      chronic diarrhea. In a different context, HMO need to be both fucosylated and
      sialylated to reduce selectin-mediated leukocyte rolling, adhesion, and
      activation, which may protect breast-fed infants from excessive immune responses.
      In addition, our most recent data show that a single HMO that carries not 1 but 2
      sialic acids protects neonatal rats from necrotizing enterocolitis, one of the
      most common and often fatal intestinal disorders in preterm infants.
      Oligosaccharides currently added to infant formula are structurally different
      from the oligosaccharides naturally occurring in human milk. Thus, it appears
      unlikely that they can mimic some of the structure-specific effects of HMO.
      Recent advances in glycan synthesis and isolation have increased the availability
      of certain HMO tri- and tetrasaccharides for in vitro and in vivo preclinical
      studies. In the end, intervention studies are needed to confirm that the
      structure-specific effects observed at the laboratory bench translate into
      benefits for the human infant. Ultimately, breastfeeding remains the number one
      choice to nourish and nurture our infants.

PMID- 22585917
TI  - Sialic acid utilization.
AB  - Early postnatal development encounters milk as a key environmental variable and
      yet the sole nutrient source. One evolutionary conserved constituent of milk is
      sialic acid, which is generally displayed on glycoconjugates and free glycans.
      During early postnatal development, high sialic acid need was proposed to be
      unmet by the endogenous sialic acid synthetic capacity. Hence, milk sialic acid
      was proposed to serve as a conditional nutrient for the newborn. In the elderly,
      at the other end of ontogeny, decreased sialylation in the brain, saliva, and
      immune system is observed. Analogous to the neonatal situation, the endogenous
      synthetic capacity may be unable to keep up with the need in this age group. The
      data discussed here propose a functional dietary role of sialic acid as a
      building block for sialylation and beyond.

PMID- 22585918
TI  - Milk oligosaccharides and metabolism in infants.
AB  - Since the discovery of human milk oligosaccharides (HMO) >60 y ago, research has
      faced major challenges including (i) the development of methods to identify and
      characterize these components, (ii) the need to use HMO fractions for functional
      studies because single HMO were not available, (iii) the uncertainty of the
      purity of HMO fractions that were often "contaminated" by remainders of lactose,
      proteins, or glycoproteins, and (iv) the low availability of large quantities of
      a single HMO for animal and human studies. In the past 10 years, there has been
      tremendous progress in all of these areas, particularly in the development of
      methods for detailed structural analysis in extremely low milk volumes. The
      greatest success, however, is that biotechnological means are available today to
      produce large amounts even of a single HMO in a purity that allows human studies
      to be performed in the future. In this review, we summarize the current knowledge
      about the metabolic aspects of HMO in infants starting with the first studies by
      Lundblad and co-workers in the early 1980s. After discussing newer observations
      in recent years, the review closes with a perspective on some important questions
      regarding metabolic and functional aspects of HMO.

PMID- 22585919
TI  - Advances in analysis of human milk oligosaccharides.
AB  - Oligosaccharides in human milk strongly influence the composition of the gut
      microflora of neonates. Because it is now clear that the microflora play
      important roles in the development of the infant immune system, human milk
      oligosaccharides (HMO) are studied frequently. Milk samples contain complex
      mixtures of HMO, usually comprising several isomeric structures that can be
      either linear or branched. Traditionally, HMO profiling was performed using HPLC
      with fluorescence or UV detection. By using porous graphitic carbon liquid
      chromatography MS, it is now possible to separate and identify most of the
      isomers, facilitating linkage-specific analysis. Matrix-assisted laser desorption
      ionization time-of-flight analysis allows fast profiling, but does not allow
      isomer separation. Novel MS fragmentation techniques have facilitated structural
      characterization of HMO that are present at lower concentrations. These
      techniques now facilitate more accurate studies of HMO consumption as well as
      Lewis blood group determinations.

PMID- 22585920
TI  - A molecular basis for bifidobacterial enrichment in the infant gastrointestinal
      tract.
AB  - Bifidobacteria are commonly used as probiotics in dairy foods. Select
      bifidobacterial species are also early colonizers of the breast-fed infant colon;
      however, the mechanism for this enrichment is unclear. We previously showed that
      Bifidobacterium longum subsp. infantis is a prototypical bifidobacterial species
      that can readily utilize human milk oligosaccharides as the sole carbon source.
      MS-based glycoprofiling has revealed that numerous B. infantis strains
      preferentially consume small mass oligosaccharides, abundant in human milks.
      Genome sequencing revealed that B. infantis possesses a bias toward genes
      required to use mammalian-derived carbohydrates. Many of these genomic features
      encode enzymes that are active on milk oligosaccharides including a novel 40-kb
      region dedicated to oligosaccharide utilization. Biochemical and molecular
      characterization of the encoded glycosidases and transport proteins has further
      resolved the mechanism by which B. infantis selectively imports and catabolizes
      milk oligosaccharides. Expression studies indicate that many of these key
      functions are only induced during growth on milk oligosaccharides and not
      expressed during growth on other prebiotics. Analysis of numerous B. infantis
      isolates has confirmed that these genomic features are common among the B.
      infantis subspecies and likely constitute a competitive colonization strategy
      used by these unique bifidobacteria. By detailed characterization of the
      molecular mechanisms responsible, these studies provide a conceptual framework
      for bifidobacterial persistence and host interaction in the infant
      gastrointestinal tract mediated in part through consumption of human milk
      oligosaccharides.

PMID- 22585921
TI  - Bifidobacterial enzymes involved in the metabolism of human milk
      oligosaccharides.
AB  - Intestinal colonization of bifidobacteria is important for the health of infants.
      Human milk oligosaccharides (HMO) have been identified as growth factors for
      bifidobacteria. Recently, a bifidobacterial enzymatic system to metabolize HMO
      was identified. 1,3-beta-Galactosyl-N-acetylhexosamine phosphorylase (GLNBP, EC
      2.4.1.211), which catalyzes the reversible phosphorolysis of galacto-N-biose
      (GNB) (Galbeta1->3GalNAc)] and lacto-N-biose I (LNB) (Galbeta1->3GlcNAc), is a
      key enzyme to explain the metabolism of HMO. Infant-type bifidobacteria possess
      the intracellular pathway to specifically metabolize GNB and LNB (GNB/LNB
      pathway). Bifidobacterium bifidum possesses extracellular enzymes to liberate LNB
      from HMO. However, Bifidobacterium longum subsp. infantis imports intact HMO to
      be hydrolyzed by intracellular enzymes. Bifidobacterial enzymes related to the
      metabolism of HMO are useful tools for preparing compounds related to HMO. For
      instance, LNB and GNB were produced from sucrose and GlcNAc/GalNAc in 1 pot using
      4 bifidobacterial enzymes, including GLNBP. LNB is expected to be a selective
      bifidus factor for infant-type strains.

PMID- 22585922
TI  - Historical aspects of human milk oligosaccharides.
AB  - This review focuses on important observations regarding infant health around 1900
      when breastfeeding was not considered a matter of importance. The discovery of
      lactobacilli and bifidobacteria and their relevance for health and disease was an
      important milestone leading to a decrease in infant mortality in the first year
      of life. At the same time, pediatricians realized that the fecal composition of
      breast-fed and bottle-fed infants differed. Observations indicated that this
      difference is linked to milk composition, particularly due to the milk
      carbohydrate fraction. Circa 1930, a human milk carbohydrate fraction called
      gynolactose was identified. This was the starting point of research on human milk
      oligosaccharides (HMO). In the following years, the first HMO were identified and
      their functions investigated. Studies after 1950 focused on the identification of
      various HMO as the bifidus factor in human milk. In the following 30 years, a
      tremendous amount of research was done with regard to the characterization of
      individual HMO and HMO patterns in milk. In this short introduction to the
      history of HMO research, which ends circa 1980, some outstanding scientists in
      pediatrics and chemistry and their pioneering contributions to research in the
      field of HMO are presented.

PMID- 22585923
TI  - Human milk oligosaccharides and Lewis blood group: individual high-throughput
      sample profiling to enhance conclusions from functional studies.
AB  - Human milk oligosaccharides (HMO) are discussed to play a crucial role in an
      infant's development. Lewis blood group epitopes, in particular, seem to
      remarkably contribute to the beneficial effects of HMO. In this regard, large
      scale functional human studies could provide evidence of the variety of results
      from in vitro investigations, although increasing the amount and complexity of
      sample and data handling. Therefore, reliable screening approaches are needed. To
      predict the oligosaccharide pattern in milk, the routine serological Lewis blood
      group typing of blood samples can be applied due to the close relationship
      between the biosynthesis of HMO and the Lewis antigens on erythrocytes. However,
      the actual HMO profile of the individual samples does not necessarily correspond
      to the serological determinations. This review demonstrates the capabilities of
      merging the traditional serological Lewis blood group typing with the additional
      information provided by the comprehensive elucidation of individual HMO patterns
      by means of state-of-the-art analytics. Deduced from the association of the
      suggested HMO biosynthesis with the Lewis blood group, the matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry profiles of
      oligosaccharides in individual milk samples exemplify the advantages and the
      limitations of sample assignment to distinct groups.

PMID- 22585924
TI  - Host-microbe interactions in the neonatal intestine: role of human milk
      oligosaccharides.
AB  - The infant intestinal microbiota is shaped by genetics and environment, including
      the route of delivery and early dietary intake. Data from germ-free rodents and
      piglets support a critical role for the microbiota in regulating gastrointestinal
      and immune development. Human milk oligosaccharides (HMO) both directly and
      indirectly influence intestinal development by regulating cell proliferation,
      acting as prebiotics for beneficial bacteria and modulating immune development.
      We have shown that the gut microbiota, the microbial metatranscriptome, and
      metabolome differ between porcine milk-fed and formula-fed (FF) piglets. Our goal
      is to define how early nutrition, specifically HMO, shapes host-microbe
      interactions in breast-fed (BF) and FF human infants. We an established
      noninvasive method that uses stool samples containing intact sloughed epithelial
      cells to quantify intestinal gene expression profiles in human infants. We
      hypothesized that a systems biology approach, combining i) HMO composition of the
      mother's milk with the infant's gut gene expression and fecal bacterial
      composition, ii) gene expression, and iii short-chain fatty acid profiles would
      identify important mechanistic pathways affecting intestinal development of BF
      and FF infants in the first few months of life. HMO composition was analyzed by
      HLPC Chip/time-of-flight MS and 3 HMO clusters were identified using principle
      component analysis. Initial findings indicated that both host epithelial cell
      mRNA expression and the microbial phylogenetic profiles provided strong feature
      sets that distinctly classified the BF and FF infants. Ongoing analyses are
      designed to integrate the host transcriptome, bacterial phylogenetic profiles,
      and functional metagenomic data using multivariate statistical analyses.

PMID- 22585925
TI  - Profiles of human milk oligosaccharides and production of some human milk
      oligosaccharides in transgenic animals.
AB  - During the decade of the 1990s and the first years of the current century, our
      group embarked on a project to study and synthesize human milk oligosaccharides.
      This report describes 2 unexpected collateral observations from that endeavor.
      The first observation was the detection and confirmation of 2 rare neutral human
      milk oligosaccharides profiles that were uncovered while assessing
      oligosaccharide content in hundreds of samples of human milk. One of these lacked
      fucosylated structures altogether, and the other lacked the oligosaccharide 3
      fucosyllactose [Galbeta1-4(Fucalpha1-3)Glc]. We used glycoconjugate probes to
      determine whether the unusual profiles were mirrored by fucosylation of milk
      glycoproteins. The results show that the lack of fucosylated oligosaccharides in
      these samples corresponds to the absence of equivalent fucosylated motifs in milk
      glycoproteins. The second finding was a shortened and distinct lactation process
      in transgenic rabbits expressing the human fucosyltransferase 1. During the first
      day of lactation, these animals expressed milk that contained both lactose and 2'
      fucosylactose, but on the second day, the production of milk was severely
      diminished, and by the fourth day, no lactose was detected in their milk.
      Meanwhile, the concentration of fucosylated glycoproteins increased from the
      onset of lactation through its premature termination. These 2 findings may shed
      light on the glycobiology of milk and perhaps on mammary gland differentiation.

PMID- 22585926
TI  - Molecular mechanism underlying sialic acid as an essential nutrient for brain
      development and cognition.
AB  - The early stages of neurodevelopment in infants are crucial for establishing
      neural structures and synaptic connections that influence brain biochemistry well
      into adulthood. This postnatal period of rapid neural growth is of critical
      importance for cell migration, neurite outgrowth, synaptic plasticity, and axon
      fasciculation. These processes thus place an unusually high demand on the
      intracellular pool of nutrients and biochemical precursors. Sialic acid (Sia), a
      family of 9-carbon sugar acids, occurs in large amounts in human milk
      oligosaccharides and is an essential component of brain gangliosides and
      sialylated glycoproteins, particularly as precursors for the synthesis of the
      polysialic acid (polySia) glycan that post-translationally modify the cell
      membrane-associated neural cell adhesion molecules (NCAM). Human milk is
      noteworthy in containing exceptionally high levels of Sia-glycoconjugates. The
      predominate form of Sia in human milk is N-acetylneuraminic acid (Neu5Ac). Infant
      formula, however, contains low levels of Sia consisting of both Neu5Ac and N
      glycolyneuraminic acid (Neu5Gc). Current studies implicate Neu5Gc in several
      human inflammatory diseases. Polysialylated NCAM and neural gangliosides both
      play critical roles in mediating cell-to-cell interactions important for neuronal
      outgrowth, synaptic connectivity, and memory formation. A diet rich in Sia also
      increases the level of Sia in the brains of postnatal piglets, the expression
      level of 2 learning-related genes, and enhances learning and memory.

PMID- 22585927
TI  - The predominance of type I oligosaccharides is a feature specific to human breast
      milk.
AB  - Human milk and colostrum contain ~12-13 g/L and ~22-24 g/L of oligosaccharides,
      respectively. The chemical structures of >100 human milk oligosaccharides (HMO)
      have been characterized to date. We determined the concentrations of 10 neutral
      and 9 acidic colostrum HMO collected during the first 3 d of lactation by using
      reverse phase HPLC after derivatization with 2-aminopyridine or 1-methyl-3-phenyl
      5-pyrazolon. The predominant oligosaccharides were Fuc(alpha1-2)Gal(beta1-4Glc
      (2'-FL), Fuc(alpha1-2)Gal(beta1-3)GlcNAc(beta1-3)Gal(beta1-4)Glc (LNFP I),
      Fuc(alpha1-2)Gal(beta1-3)[Fuc(alpha1-4)]GlcNAc(beta1-3)Gal(beta1-4)Glc (LNDFH I),
      and Gal(beta1-3)GlcNAc(beta1-3)Gal(beta1-4)Glc (LNT), the concentration of each
      of which was ~1-3 g/L. Because these HMO, other than 2'-FL, all contain the Lacto
      N-biose type I structure [Gal(beta1-3)GlcNAc], we conclude that HMO containing
      the type I structure predominate over those containing the N-acetyllactosamine
      type II structure [Gal(beta1-4)GlcNAc]. This appears to be a feature that is
      specific to humans, because the milk and colostrum of other species, including
      apes and monkeys, either contain only type II oligosaccharides or type II
      predominate over type I. It is possible that type I HMO may have importance as
      substrates for beneficial bifidobacteria in breast-fed infants. The biological
      importance of type I HMO predominance warrants further study, both in relation to
      human health and to human evolution.

PMID- 22585929
TI  - Seedlings of temperate rainforest conifer and angiosperm trees differ in leaf
      area display.
AB  - BACKGROUND AND AIMS: The contemporary relegation of conifers mainly to cold or
      infertile sites has been ascribed to low competitive ability, as a result of the
      hydraulic inefficiency of tracheids and their seedlings' initial dependence on
      small foliage areas. Here it is hypothesized that, in temperate rainforests, the
      larger leaves of angiosperms also reduce self-shading and thus enable display of
      larger effective foliage areas than the numerous small leaves of conifers.
      METHODS: This hypothesis was tested using 3-D modelling of plant architecture and
      structural equation modelling to compare self-shading and light interception
      potential of seedlings of six conifers and 12 angiosperm trees from temperate
      rainforests. The ratio of displayed leaf area to plant mass (LAR(d)) was used to
      indicate plant light interception potential: LAR(d) is the product of specific
      leaf area, leaf mass fraction, self-shading and leaf angle. RESULTS: Angiosperm
      seedlings self-shaded less than conifers, mainly because of differences in leaf
      number (more than leaf size), and on average their LAR(d) was about twice that of
      conifers. Although specific leaf area was the most pervasive influence on LAR(d),
      differences in self-shading also significantly influenced LAR(d) of large
      seedlings. CONCLUSIONS: The ability to deploy foliage in relatively few, large
      leaves is advantageous in minimizing self-shading and enhancing seedling light
      interception potential per unit of plant biomass. This study adds significantly
      to evidence that vegetative traits may be at least as important as reproductive
      innovations in explaining the success of angiosperms in productive environments
      where vegetation is structured by light competition.

PMID- 22585928
TI  - The role of milk sialyllactose in intestinal bacterial colonization.
AB  - Milk oligosaccharides influence the composition of intestinal microbiota and
      thereby mucosal inflammation. Some of the major milk oligosaccharides are
      alpha2,3-sialyllactose (3SL) and alpha2,6-sialyllactose, which are mainly
      produced by the sialyltransferases ST3GAL4 and ST6GAL1, respectively. Recently,
      we showed that mice fed milk deficient in 3SL were more resistant to dextran
      sulfate sodium-induced colitis. By contrast, the exposure to milk containing or
      deficient in 3SL had no impact on the development of mucosal leukocyte
      populations. Milk 3SL mainly affected the colonization of the intestine by
      clostridial cluster IV bacteria.

PMID- 22585930
TI  - Stem hydraulic traits and leaf water-stress tolerance are co-ordinated with the
      leaf phenology of angiosperm trees in an Asian tropical dry karst forest.
AB  - BACKGROUND AND AIMS: The co-occurring of evergreen and deciduous angiosperm trees
      in Asian tropical dry forests on karst substrates suggests the existence of
      different water-use strategies among species. In this study it is hypothesized
      that the co-occurring evergreen and deciduous trees differ in stem hydraulic
      traits and leaf water relationships, and there will be correlated evolution in
      drought tolerance between leaves and stems. METHODS: A comparison was made of
      stem hydraulic conductivity, vulnerability curves, wood anatomy, leaf life span,
      leaf pressure-volume characteristics and photosynthetic capacity of six evergreen
      and six deciduous tree species co-occurring in a tropical dry karst forest in
      south-west China. The correlated evolution of leaf and stem traits was examined
      using both traditional and phylogenetic independent contrasts correlations. KEY
      RESULTS: It was found that the deciduous trees had higher stem hydraulic
      efficiency, greater hydraulically weighted vessel diameter (D(h)) and higher mass
      based photosynthetic rate (A(m)); while the evergreen species had greater xylem
      cavitation resistance, lower leaf turgor-loss point water potential (pi(0)) and
      higher bulk modulus of elasticity. There were evolutionary correlations between
      leaf life span and stem hydraulic efficiency, A(m), and dry season pi(0). Xylem
      cavitation resistance was evolutionarily correlated with stem hydraulic
      efficiency, D(h), as well as dry season pi(0). Both wood density and leaf density
      were closely correlated with leaf water-stress tolerance and A(m). CONCLUSIONS:
      The results reveal the clear distinctions in stem hydraulic traits and leaf water
      stress tolerance between the co-occurring evergreen and deciduous angiosperm
      trees in an Asian dry karst forest. A novel pattern was demonstrated linking leaf
      longevity with stem hydraulic efficiency and leaf water-stress tolerance. The
      results show the correlated evolution in drought tolerance between stems and
      leaves.

PMID- 22585931
TI  - Serum [25(OH)D] status, ankle strength and activity show seasonal variation in
      older adults: relevance for winter falls in higher latitudes.
AB  - BACKGROUND: seasonal variation exists in serum [25(OH)D] and physical activity,
      especially at higher latitudes, and these factors impact lower limb strength.
      This study investigates seasonal variation in leg strength in a longitudinal
      repeated measures design concurrently with serum vitamin D and physical activity.
      METHODS: eighty-eight community-dwelling independently mobile older adults (69.2
      +/- 6.5 years) were evaluated five times over a year, at the end of five
      consecutive seasons at latitude 41.1 degrees S, recruited in two cohorts. Leg
      strength, serum [25(OH)D] and physical activity levels were measured. Time spent
      outside was recorded. Monthly falls diaries recorded falls. Data were analysed to
      determine annual means and percentage changes. RESULTS: significant variation in
      [25(OH)D] (+/-15%), physical activity (+/-13%), ankle dorsiflexion strength (+/
      8%) and hours spent outside (+/-20%) (all P < 0.001) was demonstrated over the
      year, with maximums in January and February (mid-summer). Low mean ankle strength
      was associated with increased incidence of falling (P = 0.047). Quadriceps
      strength did not change (+/-2%; P = 0.53). CONCLUSION: ankle dorsiflexor strength
      varied seasonally. Increased ankle strength in summer may be influenced by
      increased levels of outdoors activity over the summer months. Reduced winter-time
      dorsiflexor strength may predispose older people to increased risk of tripping
      related falls, and warrants investigation in a multi-faceted falls prevention
      programme.

PMID- 22585932
TI  - The influence of pulsed electric field on hematological parameters in rat.
AB  - The aim of the present study is to investigate whether or not pulsed electric
      field (PEF) affects some hematological parameters in rats. Sixteen healthy male
      Wistar rats weighting 150-200 g were used and were randomly divided into two
      groups. Exposure group (n = 8) was exposed to a PEF (10 kV m-1 for 1 h d-1) for
      10 consecutive days. The control group rats (n = 8) were not exposed to PEF. The
      following hematological parameters were measured in both the groups: white blood
      cells (WBCs), red blood cells (RBCs), hemoglobin (Hb), hematocrit (Ht) and
      platelets (PLTs). Some of the hematological parameters under investigation were
      similar in both the groups. Exposure group, exposed for 1 h d-1 during 10
      consecutive days, induced a significant increase in the rates of WBC (p < 0.05),
      RBC (p < 0.05), Hb (p < 0.05), Ht (p < 0.05) and PLTs (p < 0.05) in blood when
      compared with control. These results suggest that PEFs affect the hematological
      parameters in rat. Results of the parameters are statistically significant.

PMID- 22585933
TI  - Protective effect of Urtica dioica on liver damage induced by biliary obstruction
      in rats.
AB  - The aim of this study was to evaluate the possible protective effects of Urtica
      dioica (UD) against liver damage in the common bile duct-ligated rats. A total of
      24 male Sprague Dawley rats were divided into three groups, namely, control, bile
      duct ligation (BDL) and BDL + received UD groups, containing eight animals in
      each group. The rats in UD-treated groups were given UD oils (2 ml/kg) once a day
      intraperitoneally for 2 weeks starting 3 days prior to BDL operation. The change
      demonstrating the bile duct proliferation and fibrosis in expanded portal tracts
      includes the extension of proliferated bile ducts into the lobules; inflammatory
      cell infiltration into the widened portal areas were observed in BDL group.
      Treatment of BDL with UD attenuated alterations in liver histology. The alpha
      smooth muscle actin, cytokeratin-positive ductular proliferation and the activity
      of terminal deoxynucleotidyl transferase dUTP nick end labeling in the BDL were
      observed to be reduced with the UD treatment. The data indicate that UD
      attenuates BDL-induced cholestatic liver injury, bile duct proliferation and
      fibrosis. 

PMID- 22585934
TI  - The genotoxic and teratogenic effects of maltitol in rats.
AB  - In the present study, the genotoxic and cytotoxic effects of the low-caloric
      artificial sweetener maltitol, which is a sugar alcohol (polyol), were
      investigated in the bone marrow cells of rats using the chromosome aberration
      (CA) test. In addition, the teratogenicity and embryotoxicity of maltitol was
      also investigated in rats. To reveal the genotoxicity and cytotoxicity of
      maltitol, rats were intraperitoneally administered 2.5, 5 and 10 g/kg body weight
      (bw) concentrations of maltitol for 6, 12 and 24 h treatment period. The pregnant
      females were intraperitoneally treated with 1, 2 and 4 g/kg bw/day concentrations
      of maltitol during the first 7 days of gestation (first trimester) to investigate
      the teratogenicity of maltitol. The embryos were collected after killing the dams
      by cervical dislocation under ether anaesthesia on gestation day 19. Maltitol did
      not induce the CA and did not decrease the mitotic index in bone marrow cells of
      rats at all concentrations and treatment periods. In addition, maltitol was not
      teratogenic; however, it decreased the foetuses weight and at the highest dose (4
      g/kg bw) caused growth retardation.

PMID- 22585935
TI  - Gene expression of Hsp70, Hsp90 and Hsp110 families in normal palate and cleft
      palate during mouse embryogenesis.
AB  - Most previous studies focused on a small number of heat shock proteins (Hsps) and
      their relationships with embryogenesis, and the actual roles of these Hsps in
      normal and abnormal embryonic development remain unclear. It was found in the
      present systemic study that except for Grp170, whose expression was not
      detectable at GD18, all 19 Hsps of Hsp70, Hsp90 and Hsp110 families were
      expressed in the normal development of embryonic palate tissue in mice, but their
      expression patterns varied with different Hsps, presenting as a correlation with
      the developmental phases. In the treatment group by all-trans retinoic acid
      (atRA), the messenger RNA (mRNA) abundance of HspA1A, HspA1L, HspA8, HspA9,
      HspA12A, HspA12B, HspA13, HspA14, Hsp90AA1, Hsp90AB1, Grp94, Trap1, Hsp105,
      Hsp110 and Grp170 was higher in the palates at GD11 (the beginning of palate
      development), the mRNA abundance of HspA1A, HspA12A and HspA12B was higher at
      GD18 (before birth) and an mRNA expression peak of HspA1L, HspA8, HspA9,
      Hsp90AA1, Grp94, Hsp110 and Grp170 was observed at GD17. The mRNA abundance of
      most genes in atRA-induced cleft palates of the treatment group was different
      from that of the control group. Grp78, HspA14 and Hsp105 were closely associated
      with the normal palate development and cleft palate in mouse embryo, possibly as
      palate development-related genes. Except Grp170, the other genes may be closely
      associated with the development of mouse palates through participating in the
      stress response process and/or the antiapoptosis process. 

PMID- 22585936
TI  - Protective role of melatonin supplementation against nicotine-induced liver
      damage in mouse.
AB  - The present study was carried out to determine histopathological effects of
      nicotine, one of the most significant components of tobacco, on mouse liver and
      ameliorative effect of melatonin on liver damage. A total of 140 mature Swiss
      Albino mice (Mus musculus) were divided into four experimental groups: control
      group, nicotine group, melatonin group and nicotine + melatonin group. Each group
      was further subdivided into seven groups (five mice each) according to the time
      of killing (12 h and days 1, 3, 5, 7, 14 and 21 after drug administration). In
      nicotine and nicotine + melatonin groups, 3 mg/kg of nicotine was injected
      intraperitoneally every day until killing. The nicotine + melatonin group was
      additionally injected with 10 mg/kg of melatonin after 30 min of nicotine
      injection. The melatonin group was injected only with 10 mg/kg of melatonin every
      day until killing. All the treatments were given 2 h before sunset, when
      melatonin receptors were active. After the last injection, five mice from each
      group were killed at 12th hour and on days 1, 3, 5, 7, 14 and 21; the livers were
      removed for histopathological processing by light microscopy. The
      histopathological results revealed time-dependent degeneration in the livers of
      mice in nicotine group. Regenerative changes in the nicotine and melatonin groups
      were observed when compared with nicotine groups.

PMID- 22585937
TI  - Factors influencing follow-up to newborn hearing screening for infants who are
      hard of hearing.
AB  - PURPOSE: To document the epidemiological characteristics of a group of children
      who are hard of hearing, identify individual predictor variables for timely
      follow-up after a failed newborn hearing screening, and identify barriers to
      follow-up encountered by families. METHOD: The authors used an accelerated
      longitudinal design to investigate outcomes for children who are hard of hearing
      in a large, multicenter study. The present study involved a subgroup of 193
      children with hearing loss who did not pass the newborn hearing screening. The
      authors used available records to capture ages of confirmation of hearing loss,
      hearing aid fitting, and entry into early intervention. Linear regression models
      were used to investigate relationships among individual predictor variables and
      age at each follow-up benchmark. RESULTS: Of several predictor variables, only
      higher levels of maternal education were significantly associated with earlier
      confirmation of hearing loss and fitting of hearing aids; severity of hearing
      loss was not. No variables were significantly associated with age of entry into
      early intervention. Each recommended benchmark was met by a majority of children,
      but only one third met all of the benchmarks within the recommended time frame.
      CONCLUSION: Results suggest that underserved communities need extra support in
      navigating steps that follow failed newborn hearing screening.

PMID- 22585938
TI  - Determining the presence or absence of middle ear disorders: an evidence-based
      systematic review on the diagnostic accuracy of selected assessment instruments.
AB  - PURPOSE: To conduct an evidence-based systematic review on the state of the
      evidence and the diagnostic accuracy of multifrequency tympanometry (MFT), 1000
      Hz tympanometry, and wideband acoustic transfer functions in determining the
      presence or absence of middle ear disorders. METHOD: A systematic search of the
      literature published between 1975 and 2011 was conducted. Articles meeting the
      selection criteria were appraised by 2 reviewers and vetted by a 3rd for
      methodological quality. RESULTS: Ten studies were included and focused on
      participants with otosclerosis or otitis media. Two studies investigated 1000 Hz
      tympanometry, 7 examined MFT, and 2 addressed wideband reflectance (WBR).
      Methodological quality varied. Positive likelihood ratios (LR+) were
      predominantly uninformative for MFT and were mixed for 1000 Hz tympanometry. LR+
      values for WBR ranged from diagnostically suggestive to informative. Negative
      likelihood ratios (LR-) for 1000 Hz tympanometry and WBR were at least
      diagnostically suggestive. LR- values for MFT were mixed, with half considered
      clinically uninformative and half considered diagnostically suggestive.
      CONCLUSIONS: Although some of the results are promising, limited evidence and
      methodological considerations restrict the conclusions that can be drawn
      regarding the diagnostic accuracy of these technologies. Additional
      investigations are needed to determine which tools can most accurately predict
      middle ear status.

PMID- 22585939
TI  - Audiologists' professional satisfaction.
AB  - PURPOSE: The authors surveyed currently practicing audiologists to evaluate their
      professional satisfaction and compared the results to a similar survey conducted
      in 1997. METHOD: The authors repeated an audiologist professional satisfaction
      survey conducted in 1997; 382 randomly chosen, currently practicing audiologists
      participated. Responses to 38 statements were on a 5-point Likert scale (5 =  
      strong agreement with a statement, 1 =   strong disagreement with a statement).
      The respondent sample was broken down into demographic subgroups, and statements
      were divided into subgroups reflecting 6 core reward areas that contribute to
      overall professional satisfaction. RESULTS: Mean group satisfaction was 3.9 (  n
      = 382;   SD = 1.01), which has remained unchanged since 1997 (  p < .05). Private
      practice audiologists' mean group satisfaction of 4.31 (  n = 80,   SD = 0.78)
      was higher than for other practice settings (  p < .05). AuD private practice
      owners' mean group satisfaction of 4.52 (  n = 46,   SD = 0.66) was higher than
      for other degrees and practice settings (  p < .05). Core reward area ratings
      differed for AuD, MA/MS, and PhD degree holders (  p < .05). Correlations between
      the average core reward area ratings and mean group satisfaction met statistical
      significance (  p < .05). CONCLUSIONS: These results have implications for goal
      setting and planning within the profession and for audiologists' career choices.

PMID- 22585940
TI  - Regulatory forum opinion piece: thresholds in toxicologic pathology.
AB  - The definition of diagnostic thresholds is an important aspect of identification
      and recording of histopathologic lesions in toxicology studies. Although the
      primary goal of the pathology examination is to identify and interpret lesions
      associated with the administration of the test article, the toxicologic
      pathologist will encounter many changes in the tissues that are variations in
      tissue morphology, tissue artifacts, and spontaneous background findings. The
      pathologist must establish appropriate thresholds to produce a comprehensive
      record of the findings so that potentially treatment-related lesions may be
      identified. However, the findings should not be so detailed as to create overly
      complex data with the appearance of differences when none exist. Care must be
      taken to be consistent in the identification and recording of background lesions,
      since they are important for historical control data, which is often used as a
      reference when interpreting findings in current studies. Insufficient or
      inconsistent recording of findings may result in a deficiency in the historical
      control data for the identification and interpretation of a finding in the
      future.

PMID- 22585941
TI  - Gender differences in chemical carcinogenesis in National Toxicology Program 2
      year bioassays.
AB  - Differences in cancer incidences between men and women are often explained by
      either differences in environmental exposures or by influences of sex hormones.
      However, there are few studies on intrinsic gender differences in susceptibility
      to chemical carcinogens. We have analyzed the National Toxicology Program (NTP)
      database for sex differences in rat responses to chemical carcinogens. We found
      that the odds that male rat bioassays were assigned a higher level of evidence
      than female rat bioassays was 1.69 (p < .001). Of 278 carcinogenic chemicals in
      the database, 201 (72%) exhibited statistical gender differences (p <= .05) in at
      least one nonreproductive organ. One hundred thirty of these 201 chemicals
      induced gender-specific tumors in male rats and 59 in female rats. Sixty-eight
      chemicals induced tumors in males but no tumors in females. Less than one third
      (i.e., 19 chemicals) induced tumors in females but not males. Male-specific
      tumors included pancreatic and skin tumors, and female-specific tumors included
      lung tumors. For some tumor sites, these differences in gender susceptibility can
      be associated with literature data on sex hormone receptor expression. In
      conclusion, gender-specific tumors were common. The male dominance is in line
      with recent human data, and the male susceptibility to carcinogens should be
      further studied.

PMID- 22585942
TI  - A review of the incidence and coincidence of uterine and mammary tumors in Wistar
      and Sprague-Dawley rats based on the RITA database and the role of prolactin.
AB  - Wistar rats are frequently selected for use in carcinogenicity studies because of
      their advantageous survival rate, which is more favorable than other strains such
      as the Sprague-Dawley (SD) strain. Uterine and mammary tumors are relatively
      common spontaneous neoplasms of both strains. We examined the incidence and
      coincidence of uterine tumors and mammary tumors in control animals of both
      strains within the RITA database. There was a strong inverse relationship between
      these tumor types in Wistar rats (p < .001). A less strong relationship was
      present in SD rats (p = .057). This association is likely to be related to
      prolactin. A short review of the role of prolactin in rats is given. These
      results are also discussed in the background of nonspecific toxicity at high dose
      levels in carcinogenicity studies above MTD levels resulting in reduction in body
      weights of >10%.

PMID- 22585943
TI  - Regulatory forum opinion piece: the role of the toxicologic pathologist in the
      postgenomic era: challenges and opportunities.
AB  - The "omics," high-throughput screening, computational modeling, and database
      mining revolutions have each arrived with euphoric expectations, considerable
      hand waving, and promises to set toxicity testing priorities and reduce reliance
      on conventional animal toxicity and carcinogenicity testing. Reflecting back on
      prior experience with other predictive approaches and alternatives, what follows
      the rush to endorse a promising new technology or different approach to
      toxicity/carcinogenicity testing is years of grinding out data for validation and
      optimization. Much of what has driven the enthusiasm for each new emerging
      technology and approach is the costly, labor-intensive, and sometimes irrelevant
      and inefficient rodent bioassay-testing paradigm. However, no one should expect
      abandonment of all animal testing for the foreseeable future, especially for
      agrochemicals and environmental xenobiotic exposures. It is reasonable to
      anticipate the future will bring still new approaches to safety testing and human
      risk assessment. In the past, each new approach has not achieved the inflated
      expectations for safety testing and human risk assessment but often has become a
      useful research tool with tangible contributions to basic biology and clinical
      medicine. The toxicologic pathologist is embedded in the matrix of a mixed
      disciplinary milieu and is faced with some critical challenges and important
      opportunities in the postgenomic decades ahead. So what advice do we give to the
      journeyman toxicologic pathologist who will hopefully function effectively in the
      postgenomic decades ahead? And what advice do we also give to the experienced
      bench pathologist confronted with emerging technologies each accompanied by a
      bewildering array of techno-jargon so that he or she can remain effective as a
      toxicologic pathology practitioner?

PMID- 22585944
TI  - Renal sympathetic denervation suppresses postapneic blood pressure rises and
      atrial fibrillation in a model for sleep apnea.
AB  - The aim of this study was to identify the relative impact of adrenergic and
      cholinergic activity on atrial fibrillation (AF) inducibility and blood pressure
      (BP) in a model for obstructive sleep apnea. Obstructive sleep apnea is
      associated with sympathovagal disbalance, AF, and postapneic BP rises. Renal
      denervation (RDN) reduces renal efferent and possibly also afferent sympathetic
      activity and BP in resistant hypertension. The effects of RDN compared with beta
      blockade by atenolol on atrial electrophysiological changes, AF inducibility, and
      BP during obstructive events and on shortening of atrial effective refractory
      period (AERP) induced by high-frequency stimulation of ganglionated plexi were
      investigated in 20 anesthetized pigs. Tracheal occlusion with applied negative
      tracheal pressure (NTP; at -80 mbar) induced pronounced AERP shortening and
      increased AF inducibility in all of the pigs. RDN but not atenolol reduced NTP
      induced AF-inducibility (20% versus 100% at baseline; P=0.0001) and attenuated
      NTP-induced AERP shortening more than atenolol (27+/-5 versus 43+/-3 ms after
      atenolol; P=0.0272). Administration of atropine after RDN or atenolol completely
      inhibited NTP-induced AERP shortening. AERP shortening induced by high-frequency
      stimulation of ganglionated plexi was not influenced by RDN, suggesting that
      changes in sensitivity of ganglionated plexi do not play a role in the
      antiarrhythmic effect of RDN. Postapneic BP rise was inhibited by RDN and not
      modified by atenolol. We showed that vagally mediated NTP-induced AERP shortening
      is modulated by RDN or atenolol, which emphasizes the importance of autonomic
      disbalance in obstructive sleep apnea-associated AF. Renal denervation displays
      antiarrhythmic effects by reducing NTP-induced AERP shortening and inhibits
      postapneic BP rises associated with obstructive events.

PMID- 22585946
TI  - Long-term alteration in maternal blood pressure and renal function after
      pregnancy in normal and growth-restricted rats.
AB  - Intrauterine growth restriction is associated with increased risk of adult
      cardiorenal diseases. Small birth weight females are more likely to experience
      complications during their own pregnancy, including pregnancy-induced
      hypertension, preeclampsia, and gestational diabetes. We determined whether the
      physiological demand of pregnancy predisposes growth-restricted females to
      cardiovascular and renal dysfunction later in life. Late gestation bilateral
      uterine vessel ligation was performed in Wistar-Kyoto rats. At 4 months,
      restricted and control female offspring were mated with normal males and
      delivered naturally (ex-pregnant). Regardless of maternal birth weight, at 13
      months, ex-pregnant females developed elevated mean arterial pressure (indwelling
      tail-artery catheter; +6 mm Hg), reduced effective renal blood flow ((14)C-PAH
      clearance; -23%), and increased renal vascular resistance (+27%) compared with
      age-matched virgins. Glomerular filtration rate ((3)H-inulin clearance) was not
      different across groups. This adverse cardiorenal phenotype in ex-pregnant
      females was associated with elevated systemic (+57%) and altered intrarenal
      components of the renin-angiotensin system. After pregnancy at 13 months,
      coronary flow (Langendorff preparation) was halved in restricted females compared
      with controls, and together with reduced NO excretion, this may increase
      susceptibility to additional lifestyle challenges. Our results have implications
      for aging females who have been pregnant, suggesting long-term cardiovascular and
      renal alterations, with additional consequences for females who were small at
      birth.

PMID- 22585945
TI  - Oxidative stress contributes to sex differences in blood pressure in adult growth
      restricted offspring.
AB  - Numerous experimental studies suggest that oxidative stress contributes to the
      pathophysiology of hypertension and, importantly, that oxidative stress plays a
      more definitive role in mediating hypertension in males than in females.
      Intrauterine growth restriction induced by reduced uterine perfusion initiated at
      day 14 of gestation in the rat programs hypertension in adult male growth
      restricted offspring; yet, female growth-restricted offspring are normotensive.
      The mechanisms mediating sex differences in blood pressure in adult growth
      restricted offspring are not clear. Thus, this study tested the hypothesis that
      sex-specific differences in renal oxidative stress contribute to the regulation
      of blood pressure in adult growth-restricted offspring. A significant increase in
      blood pressure measured by telemetry in male growth-restricted offspring (P<0.05)
      was associated with a marked increase in renal markers of oxidative stress
      (P<0.05). Chronic treatment with the antioxidant Tempol had no effect on blood
      pressure in male control offspring, but it normalized blood pressure (P<0.05) and
      renal markers of oxidative stress (P<0.05) in male growth-restricted offspring
      relative to male control offspring. Renal markers of oxidative stress were not
      elevated in female growth-restricted offspring; however, renal activity of the
      antioxidant catalase was significantly elevated relative to female control
      offspring (P<0.05). Chronic treatment with Tempol did not significantly alter
      oxidative stress or blood pressure measured by telemetry in female offspring.
      Thus, these data suggest that sex differences in renal oxidative stress and
      antioxidant activity are present in adult growth-restricted offspring and that
      oxidative stress may play a more important role in modulating blood pressure in
      male but not female growth-restricted offspring.

PMID- 22585947
TI  - Cardiorespiratory fitness reduces the risk of incident hypertension associated
      with a parental history of hypertension.
AB  - Family history of hypertension increases the risk of an individual to develop
      hypertension, whereas moderate-to-high cardiorespiratory fitness has the opposite
      effect. However, the joint association of each on the development of hypertension
      is not well understood. We studied fitness and incident hypertension in 6278
      participants who were given a preventative medical examination. Thirty-three
      percent reported a parent with hypertension, and there were 1545 cases of
      incident hypertension after a mean of 4.7 years. The presence of parental
      hypertension was associated with a 28% higher risk of developing hypertension
      after adjustments for age, sex, and examination year. After further adjustments
      for smoking, alcohol intake, resting systolic and diastolic blood pressures,
      hypercholesterolemia, body mass index, physical inactivity, and fitness, there
      was a 20% higher risk associated with parental hypertension. After adjusting for
      age, sex, and examination year, both moderate and high levels of fitness were
      associated with lower risk for developing hypertension by 26% and 42%,
      respectively. In the joint analysis, individuals with both a low level of fitness
      and a parent with hypertension exhibited a 70% higher risk for developing
      hypertension compared with high fit individuals with no parental history (P =
      0.004). However, individuals with a high level of fitness and a parent with
      hypertension only experienced a 16% higher risk of developing hypertension
      compared with fit individuals with no parental history (P = 0.03). The
      significantly lower risk of developing hypertension when progressing from low- to
      high-fit groups among those with a parental history of hypertension has important
      clinical implications.

PMID- 22585948
TI  - Wave reflections, assessed with a novel method for pulse wave separation, are
      associated with end-organ damage and clinical outcomes.
AB  - We recently developed a novel method for assessment of arterial wave reflections
      (ARCSolver method): based on adopted Windkessel methods, flow curves are
      estimated from pressure waveforms, and wave separation analysis is performed,
      yielding the amplitudes of the forward and backward waves. The aim of this study
      was to investigate their clinical correlates and prognostic impact. In 725
      patients (417 men; mean age, 64 years) undergoing coronary angiography, we
      determined wave reflections from radial tonometry and transfer function-derived
      aortic waveforms using pulse wave analysis, as well as wave separation analysis.
      Measures of pulsatile arterial function were statistically significant, although
      moderately associated with markers of cardiac load and subclinic cardiac, renal,
      and aortic end-organ damage. After a median follow-up duration of 1399 days, 139
      patients reached the combined cardiovascular end point (death, myocardial
      infarction, stroke, coronary, cerebrovascular, and peripheral revascularization).
      In univariate analysis, the relative risk of the combined end point increased
      with increasing levels of incident pressure wave height, augmented pressure, and
      forward and backward wave amplitude (hazard ratio for 1 SD was 1.302, 1.236,
      1.226, and 1.276; P<0.01 for all, respectively). In multivariate analysis,
      backward wave amplitude was the most consistent predictor of the combined end
      point. Of note, its predictive value was independent of brachial systolic,
      diastolic, and mean blood pressures and was superior to brachial pulse pressure.
      In conclusion, the amplitude of the reflected wave, as assessed with a novel
      method for wave separation, is associated with hypertensive end organ damage and
      is an independent predictor of cardiovascular events in high-risk patients.

PMID- 22585949
TI  - "The nighttime might be the right time" for cardiovascular event prediction.

PMID- 22585951
TI  - Day-night dip and early-morning surge in blood pressure in hypertension:
      prognostic implications.
AB  - We investigated the relationship between the day-night blood pressure (BP) dip
      and the early morning BP surge in an cohort of 3012 initially untreated subjects
      with essential hypertension. The day-night reduction in systolic BP showed a
      direct association with the sleep trough (r = 0.564; P < 0.0001) and the
      preawakening (r = 0.554; P < 0.0001) systolic BP surge. Over a mean follow-up
      period of 8.44 years, 268 subjects developed a major cardiovascular event
      (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal
      stroke, and heart failure requiring hospitalization) and 220 subjects died. In a
      Cox model, after adjustment for predictive covariates, including age, sex,
      diabetes mellitus, cigarette smoking, total cholesterol, left ventricular
      hypertrophy on ECG, estimated glomerular filtration rate, and average 24-hour
      systolic BP, a blunted sleep trough (<= 19.5 mm Hg; quartile 1) and preawakening
      (<= 9.5 mm Hg; quartile 1) BP surge was associated with an excess risk of events
      (hazard ratio, 1.66 [95% CI, 1.14-2.42]; P = 0.009; hazard ratio, 1.71 [95% CI,
      1.12-2.71]; P = 0.013). After adjustment for the same covariates, neither the
      dipping pattern nor the measures of early morning BP surge were independent
      predictors of mortality. In conclusion, in initially untreated subjects with
      hypertension, a blunted day-night BP dip was associated with a blunted morning BP
      surge and vice versa. In these subjects, a blunted morning BP surge was an
      independent predictor of cardiovascular events, whereas an excessive BP surge did
      not portend an increased risk of events.

PMID- 22585950
TI  - Ambulatory blood pressure patterns in children with chronic kidney disease.
AB  - Ambulatory blood pressure (BP) monitoring (ABPM) is the best method of detecting
      abnormal BP in patients with chronic kidney disease (CKD), whose hypertension may
      be missed with casual BP measurements. We report ABPM findings in 332 children 1
      year after entry in the Chronic Kidney Disease in Children cohort study. All of
      the subjects underwent casual and ambulatory BP measurement. BP was categorized
      based on casual and ABPM results into normal (42%), white-coat (4%), masked
      (35%), and ambulatory (14%) hypertension. Only half of the subjects had a normal
      ABPM. BP load was elevated (>25%) in 52% (n = 172), whereas mean BP was elevated
      in 32% (n = 105). In multivariate analysis, those using an angiotensin-converting
      enzyme inhibitor were 89% more likely to have a normal ABPM than those who did
      not report using an angiotensin-converting enzyme inhibitor (odds ratio, 1.89
      [95% CI, 1.17-3.04]). For every 20% faster decline in annualized glomerular
      filtration rate change, the odds of an abnormal ABPM increased 26% (odds ratio,
      1.26 [95% CI, 0.97-1.64]). A 2.25-fold increase in urine protein:creatinine ratio
      annualized change was associated with a 39% higher odds of an abnormal ABPM (odds
      ratio, 1.39 [95% CI, 1.06-1.82]). Abnormalities on ABPM are common in children
      with chronic kidney disease and are strongly associated with known risk factors
      for end-stage renal disease. Individuals on angiotensin-converting enzyme
      inhibitors were less likely to have abnormal ABPM, suggesting a possible
      therapeutic intervention. ABPM should be used to monitor risk and guide therapy
      in children with chronic kidney disease.

PMID- 22585952
TI  - Heart rate dependence of aortic pulse wave velocity at different arterial
      pressures in rats.
AB  - Arterial stiffness, as measured by aortic pulse wave velocity (PWV), is an
      independent marker of cardiovascular disease and events in both healthy and
      diseased populations. Although some cardiovascular risk factors, such as age and
      blood pressure, show a strong association with PWV, the association between heart
      rate (HR) and PWV is not firmly established. Furthermore, this association has
      not been investigated at different arterial blood pressures. To study effects of
      HR on aortic PWV at different mean arterial pressures (MAPs), adult (12 weeks;
      n=7), male, anesthetized Sprague-Dawley rats were randomly paced at HRs of
      between 300 and 450 bpm, at 50-bpm steps. At each pacing step, aortic PWV was
      measured across a physiological MAP range of 60 to 150 mmHg by infusing sodium
      nitroprusside and phenylephrine. When compared at the same MAP, increases in HR
      resulted in significant increases in PWV at all of the MAPs >80 mmHg (ANOVA,
      P<0.05), with the greatest significant change of 6.03+/-0.93% observed in the
      range 110 to 130 mmHg. The positive significant association between HR and PWV
      remained when PWV was adjusted for MAP (ANOVA, P<0.001). These results indicate
      that HR dependency of PWV is different at higher pressures than at lower
      pressures and that HR may be a confounding factor that should be taken into
      consideration when performing analysis based on PWV measurements.

PMID- 22585953
TI  - Evaluation of HistoGelTM-embedded specimens for use in veterinary diagnostic
      pathology.
AB  - HistoGelTM is an aqueous specimen-processing gel that encapsulates and suspends
      histologic and cytologic specimens in a solidified medium. HistoGel-embedded
      specimens can then be processed and evaluated by routine histologic and
      immunohistochemical methods. This methodology has been used in human diagnostic
      pathology and is especially useful for small, friable, or viscous tissue samples
      that are difficult to process. In addition, special histochemical stains or
      immunohistochemistry can be performed on HistoGel-embedded cytologic specimens
      using standardized methods developed for histopathology. The current report
      describes several applications for HistoGel, including use with cytologic
      specimens, bone marrow aspirates, retention of tissue orientation for endoscopic
      biopsy specimens, and evaluation of friable tissues. Samples were encapsulated in
      HistoGel, fixed in 10% neutral buffered formalin, routinely processed, paraffin
      embedded, and sectioned for histochemical and immunohistochemical evaluation. The
      results of this study support the use of HistoGel in veterinary diagnostic
      pathology.

PMID- 22585954
TI  - Pathogenesis of nonsuppurative encephalitis caused by highly pathogenic Porcine
      reproductive and respiratory syndrome virus.
AB  - Since 2006, an unprecedented epidemic of highly pathogenic Porcine reproductive
      and respiratory syndrome virus (HP-PRRSV) infection has emerged and prevailed in
      mainland China, causing so called high fever disease with a nervous symptom that
      is different from typical porcine reproductive and respiratory syndrome. To
      investigate this syndrome, the brains of pigs inoculated with HP-PRRSV were
      analyzed. The nucleic acid of HP-PRRSV was detected in brains by reverse
      transcription polymerase chain reaction. Histological examination demonstrated
      nonsuppurative encephalitis with lymphohistiocytic perivascular cuffing and
      infiltration of these leukocytes into the neuropil. Furthermore, transmission
      electron microscopy revealed that the HP-PRRSV that infected the endothelial
      cells crossed the blood-brain barrier into the central nervous system then
      induced cellular damage to neurons and neuroglial cells. These results provide a
      general insight into the pathway of HP-PRRSV invasion into brain tissue and the
      pathogenesis of nonsuppurative encephalitis.

PMID- 22585955
TI  - Infection of an equine placenta with a novel mycobacterial species leading to
      abortion.
AB  - A 25-year-old pregnant American Quarter Horse mare presented with a 1-week
      history of progressively worsening vaginal discharge. Transrectal ultrasound
      revealed increased thickness of the combined uterus and placenta with evidence of
      chorioallantoic edema but no placental separation. A thickened amnion was visible
      on transabdominal ultrasound. Abortion occurred 2 days after presentation despite
      medical treatment. At necropsy, the chorioallantois had variable but diffuse
      thickening with focally extensive browning of the chorionic surface in the right
      horn and adjacent body. There were fluid-filled sacculations on the allantoic
      surface of the umbilical cord, allantoamnion, and chorioallantois associated with
      diffuse perivascular fluid microscopically. A nonbranching acid-fast bacterium
      identified as belonging to the genus Mycobacterium Runyon group IV was isolated
      from the chorioallantois and uterine fluid. Ziehl-Neelsen stain confirmed the
      presence of intracellular acid-fast bacilli in trophoblasts of the gravid horn
      and the cervical star area. The current case is unique in that the mycobacteria
      did not initiate a significant granulomatous inflammatory response in the chorion
      unless villar necrosis occurred. Sequence analysis of the 16S ribosomal RNA gene
      and the rpobeta gene, encoding the beta subunit of RNA polymerase, indicated that
      the strain of mycobacteria isolated in this case belonged to a novel species of
      rapidly growing mycobacteria and not to an established species. Mycobacteria are
      an uncommon and sporadic cause of placentitis and abortion, but should be
      suspected in cases of chronic placentitis that are not restricted to the cervical
      star area.

PMID- 22585956
TI  - Hepatic copper and iron accumulation and histologic findings in 104 feline liver
      biopsies.
AB  - In contrast to dogs, the role of copper and iron accumulation in feline hepatic
      disease remains poorly characterized. Therefore, the objective of the current
      study was to compare the amount and distribution of copper and iron accumulation
      for different disease processes in feline liver biopsies. Liver biopsies (from
      104 privately owned cats) were categorized by primary histopathologic lesion.
      Copper (by rubeanic acid) and iron (by Prussian blue) accumulation were graded by
      amounts (0-3) and location (centrilobular, midzonal, periportal, random). The
      Kruskal-Wallis test and Pearson chi-square test were used to assess differences
      in metal grade and location, respectively, between diagnostic categories.
      Histologic diagnoses were normal (n = 12), congenital (n = 6), neoplastic (n =
      16), infectious and/or inflammatory (n = 39), and other (n = 31). Hepatocellular
      iron staining was negative in 18 samples; remaining samples had grade 1 (n = 38),
      2 (n = 40), and 3 (n = 8) accumulation. Ninety-two samples were negative for
      copper; remaining samples had grade 1 (n = 5), 2 (n = 6), and 3 (n = 1)
      accumulation. No significant differences were found in the amount of iron or
      copper accumulation between the different diagnostic categories. Diagnostic
      category and the location of copper or iron accumulation were not associated.
      Hepatic iron accumulation was common and not associated with histologic
      diagnosis. Hepatocellular copper accumulation was more common in cats than
      previously reported, had a similar pattern of distribution to fibrotic changes,
      and was not present in histologically normal liver biopsies.

PMID- 22585957
TI  - Heat-related injury in lambs.
AB  - The broad spectrum of heat-related injury (HRI) and its associated lesions is
      well described in the human literature, with rare reports of similar findings in
      farm animals. In the current case series, lesions from 4 of 8 lambs that
      presented with clinical signs of heat stress are reported. Gross lesions at
      necropsy consisted of acute renal swelling and pallor in 2 of 4 lambs, muscle
      pallor in 2 of 4 lambs, and chronic bronchointerstitial pneumonia in each of the
      4 lambs. Histological lesions considered heat-related included acute renal
      tubular necrosis, pigment casts, tubular epithelial regeneration, multifocal
      myocyte degeneration, necrosis, and dropout with histiocytic influx and
      regeneration. Chronic, bronchointerstitial pneumonia, present in each lamb, was
      considered a condition predisposing to HRI. Compatibility between observed
      lesions and those reported in human beings with injury secondary to elevated body
      temperatures established a diagnosis of HRI in these animals. Diagnostic
      pathologists should consider HRI in lambs with histological evidence of renal
      tubular necrosis and/or rhabdomyolysis and even in cases where the clinical
      picture is strongly suggestive but lesions are not demonstrable.

PMID- 22585958
TI  - Spontaneously occurring multicentric basal cell carcinoma and keratoacanthomas in
      a multimammate mouse (Mastomys spp.).
AB  - A multicentric basal cell carcinoma was diagnosed in a male multimammate mouse
      (Mastomys spp.) with widespread cutaneous alterations. Macroscopically, the skin
      was thickened and extremely wrinkled. Histopathological examination showed
      multicentric expanding cell-rich tumors composed of basaloid cells interpreted as
      basal cell carcinoma. Immunohistochemistry detected strong cytokeratin 14
      positivity in the epidermal basal layer and in loosely arranged areas of these
      tumors but only a minimal positive reaction in densely packed areas of tumor
      cells. Furthermore, samples from the abdomen showed 3 nodular proliferations
      diagnosed as keratoacanthomas.

PMID- 22585959
TI  - Dermatopathy in juvenile Angus cattle due to vitamin A deficiency.
AB  - In juvenile cattle, vitamin A deficiency is reported most commonly as a
      neurological condition; only rarely are there dermatologic manifestations. In the
      current study, alopecia, severe epidermal and follicular orthokeratosis, and
      acanthosis due to hypovitaminosis A are reported in 2 of 32 Angus calves, with a
      third animal suspected. Affected animals responded to vitamin A supplementation,
      and no additional calves displayed signs. Vitamin A acts on skin by regulating
      DNA transcription in keratinocytes, reducing the number of tonofilaments and
      desmosomes, both involved in cell-to-cell adhesion. Hence, adequate levels of
      dietary vitamin A are necessary for normal keratinocyte turnover, and
      deficiencies result in retention of keratinized cells (orthokeratosis). The
      present report reminds diagnosticians to consider vitamin A deficiency in cases
      of orthokeratotic dermatopathy in cattle.

PMID- 22585960
TI  - Evaluation of the immunogenicity and vaccine potential of recombinant Plasmodium
      falciparum merozoite surface protein 8.
AB  - The C-terminal 19-kDa domain of merozoite surface protein 1 (MSP119) is the
      target of protective antibodies but alone is poorly immunogenic. Previously,
      using the Plasmodium yoelii murine model, we fused P. yoelii MSP119 (PyMSP119)
      with full-length P. yoelii merozoite surface protein 8 (MSP8). Upon immunization,
      the MSP8-restricted T cell response provided help for the production of high and
      sustained levels of protective PyMSP119- and PyMSP8-specific antibodies. Here, we
      assessed the vaccine potential of MSP8 of the human malaria parasite, Plasmodium
      falciparum. Distinct from PyMSP8, P. falciparum MSP8 (PfMSP8) contains an N
      terminal asparagine and aspartic acid (Asn/Asp)-rich domain whose function is
      unknown. Comparative analysis of recombinant full-length PfMSP8 and a truncated
      version devoid of the Asn/Asp-rich domain, PfMSP8(DeltaAsn/Asp), showed that both
      proteins were immunogenic for T cells and B cells. All T cell epitopes utilized
      mapped within rPfMSP8(DeltaAsn/Asp). The dominant B cell epitopes were
      conformational and common to both rPfMSP8 and rPfMSP8(DeltaAsn/Asp). Analysis of
      native PfMSP8 expression revealed that PfMSP8 is present intracellularly in late
      schizonts and merozoites. Following invasion, PfMSP8 is found distributed on the
      surface of ring- and trophozoite-stage parasites. Consistent with a low and/or
      transient expression of PfMSP8 on the surface of merozoites, PfMSP8-specific
      rabbit IgG did not inhibit the in vitro growth of P. falciparum blood-stage
      parasites. These studies suggest that the further development of PfMSP8 as a
      malaria vaccine component should focus on the use of PfMSP8(DeltaAsn/Asp) and its
      conserved, immunogenic T cell epitopes as a fusion partner for protective domains
      of poor immunogens, including PfMSP119.

PMID- 22585961
TI  - Caenorhabditis elegans immune conditioning with the probiotic bacterium
      Lactobacillus acidophilus strain NCFM enhances gram-positive immune responses.
AB  - Although the immune response of Caenorhabditis elegans to microbial infections is
      well established, very little is known about the effects of health-promoting
      probiotic bacteria on evolutionarily conserved C. elegans host responses. We
      found that the probiotic Gram-positive bacterium Lactobacillus acidophilus NCFM
      is not harmful to C. elegans and that L. acidophilus NCFM is unable to colonize
      the C. elegans intestine. Conditioning with L. acidophilus NCFM significantly
      decreased the burden of a subsequent Enterococcus faecalis infection in the
      nematode intestine and prolonged the survival of nematodes exposed to pathogenic
      strains of E. faecalis and Staphylococcus aureus, including multidrug-resistant
      (MDR) isolates. Preexposure of nematodes to Bacillus subtilis did not provide any
      beneficial effects. Importantly, L. acidophilus NCFM activates key immune
      signaling pathways involved in C. elegans defenses against Gram-positive
      bacteria, including the p38 mitogen-activated protein kinase pathway (via TIR-1
      and PMK-1) and the beta-catenin signaling pathway (via BAR-1). Interestingly,
      conditioning with L. acidophilus NCFM had a minimal effect on Gram-negative
      infection with Pseudomonas aeruginosa or Salmonella enterica serovar Typhimurium
      and had no or a negative effect on defense genes associated with Gram-negative
      pathogens or general stress. In conclusion, we describe a new system for the
      study of probiotic immune agents and our findings demonstrate that probiotic
      conditioning with L. acidophilus NCFM modulates specific C. elegans immunity
      traits.

PMID- 22585963
TI  - Interactions between polymorphonuclear leukocytes and Pseudomonas aeruginosa
      biofilms on silicone implants in vivo.
AB  - Chronic infections with Pseudomonas aeruginosa persist because the bacterium
      forms biofilms that are tolerant to antibiotic treatment and the host immune
      response. Scanning electron microscopy and confocal laser scanning microscopy
      were used to visualize biofilm development in vivo following intraperitoneal
      inoculation of mice with bacteria growing on hollow silicone tubes, as well as to
      examine the interaction between these bacteria and the host innate immune
      response. Wild-type P. aeruginosa developed biofilms within 1 day that trapped
      and caused visible cavities in polymorphonuclear leukocytes (PMNs). In contrast,
      the number of cells of a P. aeruginosa rhlA mutant that cannot produce
      rhamnolipids was significantly reduced on the implants by day 1, and the bacteria
      were actively phagocytosed by infiltrating PMNs. In addition, we identified
      extracellular wire-like structures around the bacteria and PMNs, which we found
      to consist of DNA and other polymers. Here we present a novel method to study a
      pathogen-host interaction in detail. The data presented provide the first direct,
      high-resolution visualization of the failure of PMNs to protect against bacterial
      biofilms.

PMID- 22585962
TI  - Expansion of variant diversity associated with a high prevalence of pathogen
      strain superinfection under conditions of natural transmission.
AB  - Superinfection occurs when a second, genetically distinct pathogen strain infects
      a host that has already mounted an immune response to a primary strain. For
      antigenically variant pathogens, the primary strain itself expresses a broad
      diversity of variants over time. Thus, successful superinfection would require
      that the secondary strain express a unique set of variants. We tested this
      hypothesis under conditions of natural transmission in both temperate and
      tropical regions where, respectively, single-strain infections and strain
      superinfections of the tick-borne pathogen Anaplasma marginale predominate. Our
      conclusion that strain superinfection is associated with a significant increase
      in variant diversity is supported by progressive analysis of variant composition:
      (i) animals with naturally acquired superinfection had a statistically
      significantly greater number of unique variant sequences than animals either
      experimentally infected with single strains or infected with a single strain
      naturally, (ii) the greater number of unique sequences reflected a statistically
      significant increase in primary structural diversity in the superinfected
      animals, and (iii) the increase in primary structural diversity reflected
      increased combinations of the newly identified hypervariable microdomains. The
      role of population immunity in establishing temporal and spatial patterns of
      infection and disease has been well established. The results of the present
      study, which examined strain structure under conditions of natural transmission
      and population immunity, support that high levels of endemicity also drive
      pathogen divergence toward greater strain diversity.

PMID- 22585964
TI  - The hydrophilic translocator for Vibrio parahaemolyticus, T3SS2, is also
      translocated.
AB  - The pathogenesis of the diarrheal disease caused by Vibrio parahaemolyticus, a
      leading cause of seafood-associated enteritis worldwide, is dependent upon a type
      III secretion system, T3SS2. This apparatus enables the pathogen to inject
      bacterial proteins (effectors) into the cytosol of host cells and thereby
      modulate host processes. T3SS effector proteins transit into the host cell via a
      membrane pore (translocon) typically formed by 3 bacterial proteins. We have
      identified the third translocon protein for T3SS2: VopW, which was previously
      classified as an effector protein for a homologous T3SS in V. cholerae. VopW is a
      hydrophilic translocon protein; like other such proteins, it is not inserted into
      the host cell membrane but is required for insertion of the two hydrophobic
      translocators, VopB2 and VopD2, that constitute the membrane channel. VopW is not
      required for secretion of T3SS2 effectors into the bacterial culture medium;
      however, it is essential for transfer of these proteins into the host cell
      cytoplasm. Consequently, deletion of vopW abrogates the virulence of V.
      parahaemolyticus in several animal models of diarrheal disease. Unlike previously
      described hydrophilic translocators, VopW is itself translocated into the host
      cell cytoplasm, raising the possibility that it functions as both a translocator
      and an effector.

PMID- 22585965
TI  - The intermediate region of Helicobacter pylori VacA is a determinant of toxin
      potency in a Jurkat T cell assay.
AB  - Colonization of the human stomach with Helicobacter pylori is a risk factor for
      peptic ulceration, noncardia gastric adenocarcinoma, and gastric lymphoma. The
      secreted VacA toxin is an important H. pylori virulence factor that causes
      multiple alterations in gastric epithelial cells and T cells. Several families of
      vacA alleles have been described, and H. pylori strains containing certain vacA
      types (s1, i1, and m1) are associated with an increased risk of gastric disease,
      compared to strains containing other vacA types (s2, i2, and m2). Thus far, there
      has been relatively little study of the role of the VacA intermediate region (i
      region) in toxin activity. In this study, we compared the ability of i1 and i2
      forms of VacA to cause functional alterations in Jurkat cells. To do this, we
      manipulated the chromosomal vacA gene in two H. pylori strains to introduce
      alterations in the region encoding the VacA i-region. We did not detect any
      differences in the capacity of i1 and i2 forms of VacA to cause vacuolation of
      RK13 cells. In comparison to i1 forms of VacA, i2 forms of VacA had a diminished
      capacity to inhibit the activation of nuclear factor of activated T cells (NFAT)
      and suppress interleukin-2 (IL-2) production. Correspondingly, i2 forms of VacA
      bound to Jurkat cells less avidly than did i1 forms of VacA. These results
      indicate that the VacA i-region is an important determinant of VacA effects on
      human T cell function.

PMID- 22585967
TI  - Edwardsiella tarda Eta1, an in vivo-induced antigen that is involved in host
      infection.
AB  - Edwardsiella tarda, a Gram-negative bacterium, is a severe fish pathogen that can
      also infect humans. In this study, we identified, via in vivo-induced antigen
      technology, an E. tarda antigen, Eta1, and analyzed its function in a Japanese
      flounder (Paralichthys olivaceus) model. Eta1 is composed of 226 residues and
      shares homology with putative bacterial adhesins. Quantitative real-time reverse
      transcriptase (RT)-PCR analysis indicated that when cultured in vitro, eta1
      expression was growth phase dependent and reached maximum at mid-logarithmic
      phase. During infection of flounder lymphocytes, eta1 expression was drastically
      increased at the early stage of infection. Compared to the wild type, the eta1
      defective mutant, TXeta1, was unaffected in growth but exhibited attenuated
      overall virulence, reduced tissue dissemination and colonization capacity, and
      impaired ability to invade flounder lymphocytes and to block the immune response
      of host cells. The lost virulence of TXeta1 was restored when a functional eta1
      gene was reintroduced into the strain. Western blot and immunodetection analyses
      showed that Eta1 is localized to the outer membrane and exposed on the surface of
      E. tarda and that recombinant Eta1 (rEta1) was able to interact with flounder
      lymphocytes. Consistent with these observations, antibody blocking of Eta1
      inhibited E. tarda infection at the cellular level. Furthermore, when used as a
      subunit vaccine, rEta1 induced strong protective immunity in flounder against
      lethal E. tarda challenge. Taken together, these results indicate that Eta1 is an
      in vivo-induced antigen that mediates pathogen-host interaction and, as a result,
      is required for optimal bacterial infection.

PMID- 22585966
TI  - YghG (GspSbeta) is a novel pilot protein required for localization of the
      GspSbeta type II secretion system secretin of enterotoxigenic Escherichia coli.
AB  - The enterotoxigenic Escherichia coli (ETEC) pathotype, characterized by the
      prototypical strain H10407, is a leading cause of morbidity and mortality in the
      developing world. A major virulence factor of ETEC is the type II secretion
      system (T2SS) responsible for secretion of the diarrheagenic heat-labile
      enterotoxin (LT). In this study, we have characterized the two type II secretion
      systems, designated alpha (T2SS(alpha)) and beta (T2SS(beta)), encoded in the
      H10407 genome and describe the prevalence of both systems in other E. coli
      pathotypes. Under laboratory conditions, the T2SS(beta) is assembled and
      functional in the secretion of LT into culture supernatant, whereas the
      T2SS(alpha) is not. Insertional inactivation of the three genes located upstream
      of gspC(beta) (yghJ, pppA, and yghG) in the atypical T2SS(beta) operon revealed
      that YghJ is not required for assembly of the GspD(beta) secretin or secretion of
      LT, that PppA is likely the prepilin peptidase required for the function of
      T2SS(beta), and that YghG is required for assembly of the GspD(beta) secretin and
      thus function of the T2SS(beta). Mutational and physiological analysis further
      demonstrated that YghG (redesignated GspS(beta)) is a novel outer membrane
      pilotin protein that is integral for assembly of the T2SS(beta) by localizing
      GspD(beta) to the outer membrane, whereupon GspD(beta) forms the macromolecular
      secretin multimer through which T2SS(beta) substrates are translocated.

PMID- 22585968
TI  - Differential contribution of Bacillus anthracis toxins to pathogenicity in two
      animal models.
AB  - The virulence of Bacillus anthracis, the causative agent of anthrax, stems from
      its antiphagocytic capsule, encoded by pXO2, and the tripartite toxins encoded by
      pXO1. The accepted paradigm states that anthrax is both an invasive and
      toxinogenic disease and that the toxins play major roles in pathogenicity. We
      tested this assumption by a systematic study of mutants with combined deletions
      of the pag, lef, and cya genes, encoding protective antigen (PA), lethal factor
      (LF), and edema factor (EF), respectively. The resulting seven mutants (single,
      double, and triple) were evaluated following subcutaneous (s.c.) and intranasal
      (i.n.) inoculation in rabbits and guinea pigs. In the rabbit model, virulence is
      completely dependent on the presence of PA. Any mutant bearing a pag deletion
      behaved like a pXO1-cured mutant, exhibiting complete loss of virulence with
      attenuation indices of over 2,500,000 or 1,250 in the s.c. or i.n. route of
      infection, respectively. In marked contrast, in guinea pigs, deletion of pag or
      even of all three toxin components resulted in relatively moderate attenuation,
      whereas the pXO1-cured bacteria showed complete attenuation. The results indicate
      that a pXO1-encoded factor(s), other than the toxins, has a major contribution to
      the virulence mechanism of B. anthracis in the guinea pig model. These unexpected
      toxin-dependent and toxin-independent manifestations of pathogenicity in
      different animal models emphasize the importance and need for a comprehensive
      evaluation of B. anthracis virulence in general and in particular for the design
      of relevant next-generation anthrax vaccines.

PMID- 22585970
TI  - Human impact in naturally patched small populations: genetic structure and
      conservation of the burrowing rodent, tuco-tuco (Ctenomys lami).
AB  - Isolated or semi-isolated small populations are commonly found among species, due
      to a naturally patchy occupancy of suitable habitats or also as a result of
      habitat alterations. These populations are subject to an increased risk of local
      extinction because they are more vulnerable to demographic, genetic, and
      environmental stochasticity. Considering that natural areas have been becoming
      progressively more fragmented and smaller, understanding the genetic structure
      and evolutionary dynamics of small populations is critical. Ctenomys lami has 26
      karyotypes distributed in a small area (936 km(2)) continually modified by human
      actions. We assessed the genetic geographical structure of this species,
      examining 178 specimens sampled on a fine scale, using information from
      chromosomal variability, mitochondrial DNA control region and cytochrome c
      oxidase subunit I sequences, and 14 microsatellite loci. The observed isolation
      by-distance pattern and a clinal genetic variation suggest a stepping-stone
      population model. The results did not indicate genetic structuring associated
      with distinct karyotypes. However, mitochondrial and nuclear molecular markers
      demonstrated the existence of 2 demes, which are not completely isolated but are
      probably reinforced by a geographical barrier. The vulnerability of C. lami is
      greater than previously supposed, and our data support the designation of one
      Evolutionary Significant Unit and one Management Unit, and also the inclusion of
      this species' conservation status as vulnerable.

PMID- 22585973
TI  - FDA issues guidelines for biosimilar drugs.

PMID- 22585969
TI  - Glutathione/thioredoxin systems modulate mitochondrial H2O2 emission: an
      experimental-computational study.
AB  - The net emission of hydrogen peroxide (H(2)O(2)) from mitochondria results from
      the balance between reactive oxygen species (ROS) continuously generated in the
      respiratory chain and ROS scavenging. The relative contribution of the two major
      antioxidant systems in the mitochondrial matrix, glutathione (GSH) and
      thioredoxin (Trx), has not been assessed. In this paper, we examine this key
      question via combined experimental and theoretical approaches, using isolated
      heart mitochondria from mouse, rat, and guinea pig. As compared with untreated
      control mitochondria, selective inhibition of Trx reductase with auranofin along
      with depletion of GSH with 2,4-dinitrochlorobenzene led to a species-dependent
      increase in H(2)O(2) emission flux of 17, 11, and 6 fold in state 4 and 15, 7,
      and 8 fold in state 3 for mouse, rat, and guinea pig mitochondria, respectively.
      The maximal H(2)O(2) emission as a percentage of the total O(2) consumption flux
      was 11%/2.3% for mouse in states 4 and 3 followed by 2%/0.25% and 0.74%/0.29% in
      the rat and guinea pig, respectively. A minimal computational model accounting
      for the kinetics of GSH/Trx systems was developed and was able to simulate
      increase in H(2)O(2) emission fluxes when both scavenging systems were inhibited
      separately or together. Model simulations suggest that GSH/Trx systems act in
      concert. When the scavenging capacity of either one of them saturates during
      H(2)O(2) overload, they relieve each other until complete saturation, when
      maximal ROS emission occurs. Quantitatively, these results converge on the idea
      that GSH/Trx scavenging systems in mitochondria are both essential for keeping
      minimal levels of H(2)O(2) emission, especially during state 3 respiration, when
      the energetic output is maximal. This suggests that the very low levels of
      H(2)O(2) emission observed during forward electron transport in the respiratory
      chain are a result of the well-orchestrated actions of the two antioxidant
      systems working continuously to offset ROS production.

PMID- 22585974
TI  - Cornering cancer cells.

PMID- 22585975
TI  - Pancreas cells move out before tumors form.

PMID- 22585977
TI  - Q&A: Alan Auerbach on small and speedy biotechs. Interview by Eric Bender.

PMID- 22585978
TI  - Venture capital arms flex their muscle.

PMID- 22585979
TI  - Breast cancer screening goes personalized.

PMID- 22585990
TI  - USP2a activation of MYC in prostate cancer.
AB  - Ubiquitin-specific protease 2a, a deubiquitinating enzyme, elevates MYC levels in
      prostate cancer cells via its stabilization of MDM2, undermining p53 regulation
      of microRNAs that target MYC mRNA.

PMID- 22585991
TI  - Drug interactions: the importance of looking inside cancer cells.
AB  - nab-Paclitaxel increased intratumoral gemcitabine levels by reactive oxygen
      species-mediated degradation of cytidine deaminase, the rate-limiting enzyme in
      gemcitabine inactivation. This not only has implications for how this drug
      combination mediates anticancer effects but also demonstrates the importance of
      evaluating mechanisms of drug activity within malignant cells.

PMID- 22585992
TI  - Anti-VEGF therapy revived by c-Met inhibition, but is c-Met the answer?
AB  - A new study by Sennino and colleagues demonstrates that selective VEGF inhibition
      via the use of an anti-VEGF antibody is sufficient to increase invasion and
      metastasis in a c-Met-dependent manner. Anti-VEGF therapy induced tumor hypoxia,
      hypoxia-inducible factor 1alpha, and c-Met activation in the RIP-Tag2 model of
      neuroendocrine pancreatic cancer. Selective c-Met inhibition was sufficient to
      block these effects, providing a potential mechanism for and solution to overcome
      increased invasion in the face of anti-VEGF therapy.

PMID- 22585993
TI  - Circumventing cancer drug resistance in the era of personalized medicine.
AB  - All successful cancer therapies are limited by the development of drug
      resistance. The increase in the understanding of the molecular and biochemical
      bases of drug efficacy has also facilitated studies elucidating the mechanism(s)
      of drug resistance. Experimental approaches that can help predict the eventual
      clinical drug resistance, coupled with the evolution of systematic genomic and
      proteomic technologies, are rapidly identifying novel resistance mechanisms. In
      this review, we provide a historical background on drug resistance and a
      framework for understanding the common ways by which cancers develop resistance
      to targeted therapies. We further discuss advantages and disadvantages of
      experimental strategies that can be used to identify drug resistance
      mechanism(s). SIGNIFICANCE: Increased knowledge of drug resistance mechanisms
      will aid in the development of effective therapies for patients with cancer. We
      provide a summary of current knowledge on drug resistance mechanisms and
      experimental strategies to identify and study additional drug resistance
      pathways.

PMID- 22585994
TI  - MYC is activated by USP2a-mediated modulation of microRNAs in prostate cancer.
AB  - Ubiquitin-specific protease 2a (USP2a) is overexpressed in almost half of human
      prostate cancers and c-Myc is amplified in one third of these tumor types.
      Transgenic MYC expression drives invasive adenocarcinomas in the murine prostate.
      We show that overexpression of USP2a downregulates a set of microRNAs that
      collectively increase MYC levels by MDM2 deubiquitination and subsequent p53
      inactivation. By establishing MYC as a target of miR-34b/c, we demonstrate that
      this cluster functions as a tumor suppressor in prostate cancer cells. We
      identify a distinct mRNA signature that is enriched for MYC-regulated transcripts
      and transcription factor binding sites in USP2a overexpressing prostate cancer
      cells. We demonstrate that these genes are associated with an invasive phenotype
      in human prostate cancer and that the proliferative and invasive properties of
      USP2a overexpressing cells are MYC-dependent. These results highlight an
      unrecognized mechanism of MYC regulation in prostate cancer and suggest
      alternative therapeutic strategies in targeting MYC. SIGNIFICANCE: The
      deubiquitinating enzyme USP2a has previously been shown to be oncogenic,
      overexpressed in almost half of human prostate adenocarcinomas, and prolongs the
      half-life of targets such as fatty acid synthase, MDM2, and cyclin D1. Here, we
      highlight a new mechanism by which USP2a enhances MYC levels through the
      modulation of specific subsets of microRNAs in prostate cancer, suggesting
      alternative therapeutic strategies for targeting MYC.

PMID- 22585995
TI  - Akt/PKB-mediated phosphorylation of Twist1 promotes tumor metastasis via
      mediating cross-talk between PI3K/Akt and TGF-beta signaling axes.
AB  - Metastatic breast tumor cells display an epithelial-mesenchymal transition (EMT)
      that increases cell motility, invasion, and dissemination. Although the
      transcription factor Twist1 has been shown to contribute to EMT and cancer
      metastasis, the signaling pathways regulating Twist1 activity are poorly
      understood. Here, we show that Twist1 is ubiquitously phosphorylated in 90% of
      1,532 invasive human breast tumors. Akt/protein kinase B (PKB)-mediated Twist1
      phosphorylation promotes EMT and breast cancer metastasis by modulating its
      transcriptional target TGF-beta2, leading to enhanced TGF-beta receptor
      signaling, which in turn maintains hyperactive phosphoinositide 3-kinase
      (PI3K)/Akt signaling. Preventing phosphorylation of Twist1, as well as depletion
      of TGF-beta2, significantly impaired the metastatic potential of cancer cells in
      vivo, indicating a key role of phosphorylated Twist1 (phospho-Twist1) in
      mediating cross-talk between the PI3K/Akt and TGF-beta/Smad signaling axes that
      supports metastatic tumor development. Our results describe a novel signaling
      event linking PI3K/Akt hyperactivation in tumor cells to direct regulation of
      Twist1 activation and tumor metastasis. SIGNIFICANCE: We identified the first
      phospho-Twist1 transcriptional target TGF-beta2, which mediates cross-talk
      between PI3K/Akt and TGF-beta signaling and promotes tumor metastasis. Our
      results thus illustrate a direct role of PI3K/Akt signaling in metastatic cancer
      development and suggest that Twist1 phosphorylation could be a potential
      therapeutic target in clinical cancer treatment.

PMID- 22585996
TI  - nab-Paclitaxel potentiates gemcitabine activity by reducing cytidine deaminase
      levels in a mouse model of pancreatic cancer.
AB  - Nanoparticle albumin-bound (nab)-paclitaxel, an albumin-stabilized paclitaxel
      formulation, demonstrates clinical activity when administered in combination with
      gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma (PDA).
      The limited availability of patient tissue and exquisite sensitivity of
      xenografts to chemotherapeutics have limited our ability to address the
      mechanistic basis of this treatment regimen. Here, we used a mouse model of PDA
      to show that the coadministration of nab-paclitaxel and gemcitabine uniquely
      demonstrates evidence of tumor regression. Combination treatment increases
      intratumoral gemcitabine levels attributable to a marked decrease in the primary
      gemcitabine metabolizing enzyme, cytidine deaminase. Correspondingly, paclitaxel
      reduced the levels of cytidine deaminase protein in cultured cells through
      reactive oxygen species-mediated degradation, resulting in the increased
      stabilization of gemcitabine. Our findings support the concept that suboptimal
      intratumoral concentrations of gemcitabine represent a crucial mechanism of
      therapeutic resistance in PDA and highlight the advantages of genetically
      engineered mouse models in preclinical therapeutic trials. SIGNIFICANCE: This
      study provides mechanistic insight into the clinical cooperation observed between
      gemcitabine and nab-paclitaxel in the treatment of pancreatic cancer.

PMID- 22585998
TI  - Mutations, tissue type both influence cancer metabolism.
AB  - Research in mice shows that the metabolism of glucose and glutamine differs
      between liver tumors induced by the 2 oncogenes Myc and Met, and between lung and
      liver tumors induced by Myc.

PMID- 22585997
TI  - Suppression of tumor invasion and metastasis by concurrent inhibition of c-Met
      and VEGF signaling in pancreatic neuroendocrine tumors.
AB  - Invasion and metastasis increase after the inhibition of VEGF signaling in some
      preclinical tumor models. In the present study we asked whether selective VEGF
      inhibition is sufficient to increase invasion and metastasis and whether
      selective c-Met inhibition is sufficient to block this effect. Treatment of
      pancreatic neuroendocrine tumors in RIP-Tag2 mice with a neutralizing anti-VEGF
      antibody reduced tumor burden but increased tumor hypoxia, hypoxia-inducible
      factor-1alpha, and c-Met activation and also increased invasion and metastasis.
      However, invasion and metastasis were reduced by concurrent inhibition of c-Met
      by PF-04217903 or PF-02341066 (crizotinib). A similar benefit was found in
      orthotopic Panc-1 pancreatic carcinomas treated with sunitinib plus PF-04217903
      and in RIP-Tag2 tumors treated with XL184 (cabozantinib), which simultaneously
      blocks VEGF and c-Met signaling. These findings document that invasion and
      metastasis are promoted by selective inhibition of VEGF signaling and can be
      reduced by the concurrent inhibition of c-Met. SIGNIFICANCE: This report examines
      the mechanism of increased tumor aggressiveness after anti-VEGF therapy and
      presents evidence for roles of vascular pruning, hypoxia, and c-Met activation.
      The results show that simultaneous inhibition of c-Met and VEGF signaling not
      only slows tumor growth but also reduces invasion and metastasis.

PMID- 22585999
TI  - Tracking down tumor-targeting bacteria.
AB  - Bioluminescent imaging in mice is said to produce the first accurately localized
      3-dimensional in vivo images of bacteria in tumors.

PMID- 22586000
TI  - Antiangiogenic drugs increase xenograft aggressiveness.
AB  - Treating human breast cancer xenografts in mice with bevacizumab or sunitinib has
      increased the population of cancer stem cells found in the tumors.

PMID- 22586001
TI  - Can chemotherapy cause cancer relapse?
AB  - Deep whole-genome sequencing of primary tumors in acute myeloid leukemia has
      revealed evidence that chemotherapy can lead to new mutations that may drive
      resistance.

PMID- 22586005
TI  - Some cells in a tumor protect against metastasis.
AB  - Depleting pericytes from a tumor can shrink the mass, but doing so may also make
      the tumor more aggressive and increase its odds of metastasizing.

PMID- 22586006
TI  - A comprehensive care management program to prevent chronic obstructive pulmonary
      disease hospitalizations: a randomized, controlled trial.
AB  - BACKGROUND: Improving a patient's ability to self-monitor and manage changes in
      chronic obstructive pulmonary disease (COPD) symptoms may improve outcomes.
      OBJECTIVE: To determine the efficacy of a comprehensive care management program
      (CCMP) in reducing the risk for COPD hospitalization. DESIGN: A randomized,
      controlled trial comparing CCMP with guideline-based usual care.
      (ClinicalTrials.gov registration number: NCT00395083) SETTING: 20 Veterans
      Affairs hospital-based outpatient clinics. PARTICIPANTS: Patients hospitalized
      for COPD in the past year. INTERVENTION: The CCMP included COPD education during
      4 individual sessions and 1 group session, an action plan for identification and
      treatment of exacerbations, and scheduled proactive telephone calls for case
      management. Patients in both the intervention and usual care groups received a
      COPD informational booklet; their primary care providers received a copy of COPD
      guidelines and were advised to manage their patients according to these
      guidelines. Patients were randomly assigned, stratifying by site based on random,
      permuted blocks of variable size. MEASUREMENTS: The primary outcome was time to
      first COPD hospitalization. Staff blinded to study group performed telephone
      based assessment of COPD exacerbations and hospitalizations, and all
      hospitalizations were blindly adjudicated. Secondary outcomes included non-COPD
      health care use, all-cause mortality, health-related quality of life, patient
      satisfaction, disease knowledge, and self-efficacy. RESULTS: Of the eligible
      patients, 209 were randomly assigned to the intervention group and 217 to the
      usual care group. Citing serious safety concerns, the data monitoring committee
      terminated the intervention before the trial's planned completion after 426 (44%)
      of the planned total of 960 patients were enrolled. Mean follow-up was 250 days.
      When the study was stopped, the 1-year cumulative incidence of COPD-related
      hospitalization was 27% in the intervention group and 24% in the usual care group
      (hazard ratio, 1.13 [95% CI, 0.70 to 1.80]; P= 0.62). There were 28 deaths from
      all causes in the intervention group versus 10 in the usual care group (hazard
      ratio, 3.00 [CI, 1.46 to 6.17]; P= 0.003). Cause could be assigned in 27 (71%)
      deaths. Deaths due to COPD accounted for the largest difference: 10 in the
      intervention group versus 3 in the usual care group (hazard ratio, 3.60 [CI, 0.99
      to 13.08]; P= 0.053). LIMITATIONS: Available data could not fully explain the
      excess mortality in the intervention group. Ability to assess the quality of the
      educational sessions provided by the case managers was limited. CONCLUSION: A
      CCMP in patients with severe COPD had not decreased COPD-related hospitalizations
      when the trial was stopped prematurely. The CCMP was associated with
      unanticipated excess mortality, results that differ markedly from similar
      previous trials. A data monitoring committee should be considered in the design
      of clinical trials involving behavioral interventions.

PMID- 22586007
TI  - A multidimensional index and staging system for idiopathic pulmonary fibrosis.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung
      disease with an overall poor prognosis. A simple-to-use staging system for IPF
      may improve prognostication, help guide management, and facilitate research.
      OBJECTIVE: To develop a multidimensional prognostic staging system for IPF by
      using commonly measured clinical and physiologic variables. DESIGN: A clinical
      prediction model was developed and validated by using retrospective data from 3
      large, geographically distinct cohorts. SETTING: Interstitial lung disease
      referral centers in California, Minnesota, and Italy. PATIENTS: 228 patients with
      IPF at the University of California, San Francisco (derivation cohort), and 330
      patients at the Mayo Clinic and Morgagni-Pierantoni Hospital (validation cohort).
      MEASUREMENTS: The primary outcome was mortality, treating transplantation as a
      competing risk. Model discrimination was assessed by the c-index, and calibration
      was assessed by comparing predicted and observed cumulative mortality at 1, 2,
      and 3 years. RESULTS: Four variables were included in the final model: gender
      (G), age (A), and 2 lung physiology variables (P) (FVC and Dlco). A model using
      continuous predictors (GAP calculator) and a simple point-scoring system (GAP
      index) performed similarly in derivation (c-index of 70.8 and 69.3, respectively)
      and validation (c-index of 69.1 and 68.7, respectively). Three stages (stages I,
      II, and III) were identified based on the GAP index with 1-year mortality of 6%,
      16%, and 39%, respectively. The GAP models performed similarly in pooled follow
      up visits (c-index >=71.9). LIMITATION: Patients were drawn from academic centers
      and analyzed retrospectively. CONCLUSION: The GAP models use commonly measured
      clinical and physiologic variables to predict mortality in patients with IPF.

PMID- 22586009
TI  - Risk for colorectal cancer in persons with a family history of adenomatous
      polyps: a systematic review.
AB  - BACKGROUND: The risk for colorectal cancer (CRC) is unclear for persons who have
      first-degree relatives with adenomatous polyps (adenomas). PURPOSE: To determine
      the validity of studies about this issue. DATA SOURCES: MEDLINE and Cochrane
      databases from 1966 through 2011. STUDY SELECTION: Sequential review of titles,
      abstracts, and text from retrieved articles. DATA EXTRACTION: Study objective,
      study design, and numbers in study groups. DATA SYNTHESIS: Ten studies were
      identified that have been used to answer the question, "Does having a first
      degree relative with an adenoma increase the risk for CRC?" We determined that
      they instead answer the question, "Does having a first-degree relative with CRC
      increase the risk for an adenoma?" We identified 2 additional studies that
      provide more relevant information. One study showed that the risk for CRC in
      persons who have first-degree relatives with adenomas is greater than the risk in
      persons who do not have first-degree relatives with adenomas (2.31% vs. 0.53%;
      relative risk, 4.36 [95% CI, 1.60 to 10.21]). The other study showed that the
      risk for CRC or large adenomas (>=1 cm) in persons who have first-degree
      relatives with large adenomas is greater than the risk in persons whose first
      degree relatives do not have adenomas or CRC (8.3% vs. 4.2%; adjusted odds ratio,
      2.27 [CI, 1.01 to 5.09]). LIMITATION: Even the 2 relevant studies have design
      problems that affect validity and generalizability. CONCLUSION: Most studies that
      are cited for the risk for CRC when relatives have adenomas do not address the
      issue. The 2 studies that do address the issue suggest an increased risk but have
      important methodological limitations. Properly designed studies are needed to
      measure the risk and identify the factors that modify it.

PMID- 22586008
TI  - Diagnostic accuracy of laxative-free computed tomographic colonography for
      detection of adenomatous polyps in asymptomatic adults: a prospective evaluation.
AB  - BACKGROUND: Colon screening by optical colonoscopy (OC) or computed tomographic
      colonography (CTC) requires a laxative bowel preparation, which inhibits
      screening participation. OBJECTIVE: To assess the performance of detecting
      adenomas 6 mm or larger and patient experience of laxative-free, computer-aided
      CTC. DESIGN: Prospective test comparison of laxative-free CTC and OC. The CTC
      included electronic cleansing and computer-aided detection. Optical colonoscopy
      examinations were initially blinded to CTC results, which were subsequently
      revealed during colonoscope withdrawal; this method permitted reexamination to
      resolve discrepant findings. Unblinded OC served as a reference standard.
      (ClinicalTrials.gov registration number: NCT01200303) SETTING: Multicenter
      ambulatory imaging and endoscopy centers. PARTICIPANTS: 605 adults aged 50 to 85
      years at average to moderate risk for colon cancer. MEASUREMENTS: Per-patient
      sensitivity and specificity of CTC and first-pass OC for detecting adenomas at
      thresholds of 10 mm or greater, 8 mm or greater, and 6 mm or greater; per-lesion
      sensitivity and survey data describing patient experience with preparations and
      examinations. RESULTS: For adenomas 10 mm or larger, per-patient sensitivity of
      CTC was 0.91 (95% CI, 0.71 to 0.99) and specificity was 0.85 (CI, 0.82 to 0.88);
      sensitivity of OC was 0.95 (CI, 0.77 to 1.00) and specificity was 0.89 (CI, 0.86
      to 0.91). Sensitivity of CTC was 0.70 (CI, 0.53 to 0.83) for adenomas 8 mm or
      larger and 0.59 (CI, 0.47 to 0.70) for those 6 mm or larger; sensitivity of OC
      for adenomas 8 mm or larger was 0.88 (CI, 0.73 to 0.96) and 0.76 (CI, 0.64 to
      0.85) for those 6 mm or larger. The specificity of OC at the threshold of 8 mm or
      larger was 0.91 and at 6 mm or larger was 0.94. Specificity for OC was greater
      than that for CTC, which was 0.86 at the threshold of 8 mm or larger and 0.88 at
      6 mm or larger (P= 0.02). Reported participant experience for comfort and
      difficulty of examination preparation was better with CTC than OC. LIMITATIONS:
      There were 3 CTC readers. The survey instrument was not independently validated.
      CONCLUSION: Computed tomographic colonography was accurate in detecting adenomas
      10 mm or larger but less so for smaller lesions. Patient experience was better
      with laxative-free CTC. These results suggest a possible role for laxative-free
      CTC as an alternate screening method.

PMID- 22586010
TI  - How variability in the institutional review board review process affects minimal
      risk multisite health services research.
AB  - BACKGROUND: The Department of Health and Human Services recently called for
      public comment on human subjects research protections. OBJECTIVE: To assess
      variability in reviews across institutional review boards (IRBs) for a multisite,
      minimal-risk trial of financial incentives for evidence-based hypertension care
      and to quantify the effect of review determinations on site participation,
      budget, and timeline. DESIGN: A natural experiment occurring from multiple IRBs
      reviewing the same protocol for a multicenter trial (May 2005 to October 2007).
      PARTICIPANTS: 25 Veterans Affairs (VA) medical centers. MEASUREMENTS: Number of
      submissions, time to approval, and costs were evaluated; patient complexity,
      academic affiliation, size, and location (urban or rural) between participating
      and nonparticipating VA medical centers were compared. RESULTS: Of 25 eligible VA
      medical centers, 6 did not meet requirements for IRB review and 2 declined to
      participate. Of 17 applications, 14 were approved. The process required 115
      submissions, lasted 27 months, and cost close to $170 000 in staff salaries. One
      IRB's concern about incentivizing a particular medication recommended by national
      guidelines prompted a change in our design to broaden our inclusion criteria
      beyond uncomplicated hypertension. The change required amending the protocol at
      14 sites to preserve internal validity. The IRBs that approved the protocol
      classified it as minimal risk. The 12 sites that ultimately participated in the
      trial were more likely to be urban and academically affiliated and to care for
      more complex patients, which limits the external validity of the trial's
      findings. LIMITATION: Because data came from a single multisite trial in the VA
      system that uses a 2-stage review process, generalizability is limited.
      CONCLUSION: Complying with IRB requirements for a minimal-risk study required
      substantial resources and threatened the study's internal and external validity.
      The current review of regulatory requirements may address some of these problems.

PMID- 22586011
TI  - Reactivation of hepatitis B during immunosuppressive therapy: potentially fatal
      yet preventable.

PMID- 22586012
TI  - Ethical dilemmas and malfunctions in clinical trials research.

PMID- 22586013
TI  - A certain gift, and a question of ethics.

PMID- 22586014
TI  - Evaluation of guidelines on diabetes medication.

PMID- 22586016
TI  - Exposing unethical human research.

PMID- 22586015
TI  - Evaluation of guidelines on diabetes medication.

PMID- 22586018
TI  - Summaries for patients. A comprehensive care management program to prevent
      chronic obstructive pulmonary disease hospitalizations.

PMID- 22586017
TI  - Successful treatment of antineutrophil cytoplasmic antibody-associated vasculitis
      with eicosapentaenoic acid.

PMID- 22586019
TI  - Summaries for patients. Screening for colon cancer by using a computed
      tomographic scan without a laxative.

PMID- 22586020
TI  - ACP Journal Club. Review: enoxaparin during PCI is better than unfractionated
      heparin for reducing mortality in coronary heart disease.

PMID- 22586021
TI  - ACP Journal Club. Low-dose rivaroxaban reduced mortality in patients with a
      recent acute coronary syndrome.

PMID- 22586022
TI  - ACP Journal Club. Enoxaparin plus idrabiotaparinux was noninferior to enoxaparin
      plus warfarin for recurrent VTE in acute PE.

PMID- 22586023
TI  - ACP Journal Club. Adding N-acetylcysteine to prednisolone reduced early mortality
      in severe alcoholic hepatitis.

PMID- 22586024
TI  - ACP Journal Club. IV salbutamol increased mortality in patients with the acute
      respiratory distress syndrome.

PMID- 22586025
TI  - ACP Journal Club. 2-cm and 4-cm surgical excision margins did not differ for
      survival in cutaneous melanoma > 2 mm thick.

PMID- 22586026
TI  - ACP Journal Club. Review: Vitamin D supplementation improves some balance
      measures but not muscle strength in older adults.

PMID- 22586027
TI  - ACP Journal Club. Review: biologic agents increase short-term risk for some
      adverse events in conditions other than HIV or AIDS.

PMID- 22586028
TI  - ACP Journal Club. Review: limited evidence suggests that clobetasol or mometasone
      is effective in genital lichen sclerosus.

PMID- 22586029
TI  - ACP Journal Club. SSRI use in late pregnancy was associated with increased
      persistent pulmonary hypertension in newborns.

PMID- 22586030
TI  - ACP Journal Club. Educational messages on laboratory results improved diastolic
      BP but not systolic BP, HbA(1C), or cholesterol in diabetes.

PMID- 22586031
TI  - ACP Journal Club. A 5-item calculator predicted risk for postoperative
      respiratory failure.

PMID- 22586032
TI  - Protein kinase C-theta promotes Th17 differentiation via upregulation of Stat3.
AB  - Although protein kinase C-theta (PKC-theta)-deficient mice are resistant to the
      induction of Th17-dependent experimental autoimmune encephalomyelitis, the
      function of PKC-theta in Th17 differentiation remains unknown. In this article,
      we show that purified, naive CD4 PKC-theta(-/-) T cells were defective in Th17
      differentiation, whereas Th1 and Th2 differentiation appeared normal. Activation
      of PKC-theta with PMA promoted Th17 differentiation in wild type (WT) but not PKC
      theta(-/-) T cells. Furthermore, PKC-theta(-/-) T cells had notably lower levels
      of Stat3, a transcription factor required for Th17 differentiation, and PMA
      markedly stimulated the expression of Stat3 in WT but not PKC-theta(-/-) T cells.
      In contrast, activation of Stat4 and Stat6, which are critical for Th1 and Th2
      differentiation, was normal in PKC-theta(-/-) T cells. Forced expression of Stat3
      significantly increased Th17 differentiation in PKC-theta(-/-) T cells,
      suggesting that reduced Stat3 levels were responsible for impaired Th17
      differentiation, and that Stat3 lies downstream of PKC-theta. Constitutively
      active PKC-theta, or WT PKC-theta activated by either PMA or TCR cross-linking,
      stimulated expression of a luciferase reporter gene driven by the Stat3 promoter.
      PKC-theta-mediated activation of the Stat3 promoter was inhibited by dominant
      negative AP-1 and IkappaB kinase-beta, but stimulated by WT AP-1 and IkappaB
      kinase-beta, suggesting that PKC-theta stimulates Stat3 transcription via the AP
      1 and NF-kappaB pathways. Lastly, conditions favoring Th17 differentiation
      induced the highest activation level of PKC-theta. Altogether, the data indicate
      that PKC-theta integrates the signals from TCR signaling and Th17 priming
      cytokines to upregulate Stat3 via NF-kappaB and AP-1, resulting in the
      stimulation of Th17 differentiation.

PMID- 22586033
TI  - 15 kDa granulysin causes differentiation of monocytes to dendritic cells but
      lacks cytotoxic activity.
AB  - Granulysin is expressed as two isoforms by human cytotoxic cells: a single mRNA
      gives rise to 15 kDa granulysin, a portion of which is cleaved to a 9 kDa
      protein. Studies with recombinant 9 kDa granulysin have demonstrated its
      cytolytic and proinflammatory properties, but much less is known about the
      biologic function of the 15 kDa isoform. In this study, we show that the
      subcellular localization and functions of 9 and 15 kDa granulysin are largely
      distinct. Nine kilodalton granulysin is confined to cytolytic granules that are
      directionally released following target cell recognition. In contrast, 15 kDa
      granulysin is located in distinct granules that lack perforin and granzyme B and
      that are released by activated cytolytic cells. Although recombinant 9 kDa
      granulysin is cytolytic against a variety of tumors and microbes, recombinant 15
      kDa granulysin is not. The 15 kDa isoform is a potent inducer of monocytic
      differentiation to dendritic cells, but the 9 kDa isoform is not. In vivo, mice
      expressing granulysin show markedly improved antitumor responses, with increased
      numbers of activated dendritic cells and cytokine-producing T cells. Thus, the
      distinct functions of granulysin isoforms have major implications for diagnosis
      and potential new therapies for human disease.

PMID- 22586034
TI  - Differential effects of denileukin diftitox IL-2 immunotoxin on NK and regulatory
      T cells in nonhuman primates.
AB  - Denileukin diftitox (DD), a fusion protein comprising IL-2 and diphtheria toxin,
      was initially expected to enhance antitumor immunity by selectively eliminating
      regulatory T cells (Tregs) displaying the high-affinity IL-2R (alpha-beta-gamma
      trimers). Although DD was shown to deplete some Tregs in primates, its effects on
      NK cells (CD16(+)CD8(+)NKG2A(+)CD3(-)), which constitutively express the
      intermediate-affinity IL-2R (beta-gamma dimers) and play a critical role in
      antitumor immunity, are still unknown. To address this question, cynomolgus
      monkeys were injected i.v. with two doses of DD (8 or 18 MUg/kg). This treatment
      resulted in a rapid, but short-term, reduction in detectable peripheral blood
      resting Tregs (CD4(+)CD45RA(+)Foxp3(+)) and a transient increase in the number of
      activated Tregs (CD4(+)CD45RA(-)Foxp3(high)), followed by their partial depletion
      (50-60%). In contrast, all NK cells were deleted immediately and durably after DD
      administration. This difference was not due to a higher binding or
      internalization of DD by NK cells compared with Tregs. Coadministration of DD
      with IL-15, which binds to IL-2Rbeta-gamma, abrogated DD-induced NK cell deletion
      in vitro and in vivo, whereas it did not affect Treg elimination. Taken together,
      these results show that DD exerts a potent cytotoxic effect on NK cells, a
      phenomenon that might impair its antitumoral properties. However,
      coadministration of IL-15 with DD could alleviate this problem by selectively
      protecting potentially oncolytic NK cells, while allowing the depletion of
      immunosuppressive Tregs in cancer patients.

PMID- 22586035
TI  - A switch in pathogenic mechanism in myelin oligodendrocyte glycoprotein-induced
      experimental autoimmune encephalomyelitis in IFN-gamma-inducible lysosomal thiol
      reductase-free mice.
AB  - IFN-gamma-inducible lysosomal thiol reductase (GILT) is an enzyme located in the
      Lamp-2-positive compartments of APC. GILT(-/-) mice are phenotypically normal,
      but their T cells exhibit reduced proliferation to several exogenously
      administered Ags that include cysteine residues and disulfide bonds. We undertook
      the present studies to determine if GILT(-/-) mice would process exogenously
      administered myelin oligodendrocyte glycoprotein (MOG), which contains disulfide
      bonds, to generate experimental autoimmune encephalomyelitis (EAE) to the
      endogenous protein. One possibility was that MOG(35-55) peptide would induce EAE,
      but that MOG protein would not. GILT(-/-) mice were relatively resistant to
      MOG(35-55)-induced EAE but slightly more susceptible to rat MOG protein-induced
      EAE than wild-type (WT) mice. Even though MOG(35-55) was immunogenic in GILT(-/-)
      mice, GILT APCs could not generate MOG(35-55) from MOG protein in vitro,
      suggesting that the endogenous MOG protein was not processed to the MOG(35-55)
      peptide in vivo. Immunization of GILT(-/-) mice with rat MOG protein resulted in
      a switch in pathogenic mechanism from that seen in WT mice; the CNS infiltrate
      included large numbers of plasma cells; and GILT(-/-) T cells proliferated to
      peptides other than MOG(35-55). In contrast to WT rat MOG-immunized mice, rat MOG
      immunized GILT(-/-) mice generated Abs that transferred EAE to MOG(35-55)-primed
      GILT(-/-) mice, and these Abs bound to oligodendrocytes. These studies,
      demonstrating the key role of a processing enzyme in autoimmunity, indicate that
      subtle phenotypic changes have profound influences on pathogenic mechanisms and
      are directly applicable to the outbred human population.

PMID- 22586037
TI  - Cutting edge: LPS-induced emergency myelopoiesis depends on TLR4-expressing
      nonhematopoietic cells.
AB  - Systemic bacterial infection is rapidly recognized as an emergency state leading
      to neutrophil release into the circulation and increased myeloid cell production
      within the bone marrow. However, the mechanisms of sensing infection and
      subsequent translation into emergency myelopoiesis have not been defined. In this
      study, we demonstrate in vivo in mice that, surprisingly, selective TLR4
      expression within the hematopoietic compartment fails to induce LPS-driven
      emergency myelopoiesis. In contrast, TLR4-expressing nonhematopoietic cells are
      indispensable for LPS-induced, G-CSF-mediated myelopoietic responses.
      Furthermore, LPS-induced emergency myelopoiesis is independent of intact IL-1RI
      signaling and, thus, does not require inflammasome activation. Collectively, our
      findings reveal a key and nonredundant role for nonhematopoietic compartment
      pathogen sensing that is subsequently translated into cytokine release for
      enhanced, demand-adapted myeloid cell production.

PMID- 22586036
TI  - Aminopeptidase substrate preference affects HIV epitope presentation and predicts
      immune escape patterns in HIV-infected individuals.
AB  - Viruses evade immune detection partly through immune-associated mutations.
      Analyses of HIV sequences derived from infected individuals have identified
      numerous examples of HLA-associated mutations within or adjacent to T cell
      epitopes, but the potential impact of most mutations on epitope production and
      presentation remains unclear. The multistep breakdown of proteins into epitopes
      includes trimming of N-extended peptides into epitopes by aminopeptidases before
      loading onto MHC class I molecules. Definition of sequence signatures that
      modulate epitope production would lead to a better understanding of factors
      driving viral evolution and immune escape at the population level. In this study,
      we identified cytosolic aminopeptidases cleavage preferences in primary cells and
      its impact on HIV Ag degradation into epitopes in primary human cell extracts by
      mass spectrometry and on epitope presentation to CTL. We observed a hierarchy of
      preferred amino acid cleavage by cytosolic aminopeptidases. We demonstrated that
      flanking mutations producing more or less cleavable motifs can increase or
      decrease epitope production and presentation by up to 14-fold. We found that the
      efficiency of epitope production correlates with cleavability of flanking
      residues. These in vitro findings were supported by in vivo population-level
      analyses of clinically derived viral sequences from 1134 antiretroviral-naive HIV
      infected individuals: HLA-associated mutations immune pressures drove the
      selection of residues that are less cleavable by aminopeptidases predominantly at
      N-flanking sites, leading to reduced epitope production and immune recognition.
      These results underscore an important and widespread role of Ag processing
      mutations in HIV immune escape and identify molecular mechanisms underlying
      impaired epitope presentation.

PMID- 22586038
TI  - Type I IFN induced by adenovirus serotypes 28 and 35 has multiple effects on T
      cell immunogenicity.
AB  - Recombinant adenovirus (rAd) vectors are being investigated as vaccine delivery
      vehicles in preclinical and clinical studies. rAds constructed from different
      serotypes differ in receptor usage, tropism, and ability to activate cells,
      aspects of which likely contribute to their different immunogenicity profiles. In
      this study, we compared the infectivity and cell stimulatory capacity of
      recombinant adenovirus serotype 5 (rAd5), recombinant adenovirus serotype 28
      (rAd28), and recombinant adenovirus serotype 35 (rAd35) in association with their
      respective immunogenicity profiles. We found that rAd28 and rAd35 infected and
      led to the in vitro maturation and activation of both human and mouse dendritic
      cells more efficiently compared with rAd5. In stark contrast to rAd5, rAd28 and
      rAd35 induced production of IFN-alpha and stimulated IFN-related intracellular
      pathways. However, the in vivo immunogenicity of rAd28 and rAd35 was
      significantly lower than that of rAd5. Deletion of IFN-alpha signaling during
      vaccination with rAd28 and rAd35 vectors increased the magnitude of the insert
      specific T cell response to levels induced by vaccination with rAd5 vector. The
      negative impact of IFN-alpha signaling on the magnitude of the T cell response
      could be overcome by increasing the vaccine dose, which was also associated with
      greater polyfunctionality and a more favorable long-term memory phenotype of the
      CD8 T cell response in the presence of IFN-alpha signaling. Taken together, our
      results demonstrate that rAd-induced IFN-alpha production has multiple effects on
      T cell immunogenicity, the understanding of which should be considered in the
      design of rAd vaccine vectors.

PMID- 22586040
TI  - Differential regulation of the Let-7 family of microRNAs in CD4+ T cells alters
      IL-10 expression.
AB  - MicroRNAs (miRNAs) are ~22-nt small RNAs that are important regulators of mRNA
      turnover and translation. Recent studies have shown the importance of the miRNA
      pathway in HIV-1 infection, particularly in maintaining latency. Our initial in
      vitro studies demonstrated that HIV-1-infected HUT78 cells expressed
      significantly higher IL-10 levels compared with uninfected cultures. IL-10 plays
      an important role in the dysregulated cytotoxic T cell response to HIV-1, and in
      silico algorithms suggested that let-7 miRNAs target IL10 mRNA. In a time course
      experiment, we demonstrated that let-7 miRNAs fall rapidly following HIV-1
      infection in HUT78 cells with concomitant rises in IL-10. To show a direct link
      between let-7 and IL-10, forced overexpression of let-7 miRNAs resulted in
      significantly reduced IL-10 levels, whereas inhibition of the function of these
      miRNAs increased IL-10. To demonstrate the relevance of these results, we focused
      our attention on CD4(+) T cells from uninfected healthy controls, chronic HIV-1
      infected patients, and long-term nonprogressors. We characterized miRNA changes
      in CD4(+) T cells from these three groups and demonstrated that let-7 miRNAs were
      highly expressed in CD4(+) T cells from healthy controls and let-7 miRNAs were
      significantly decreased in chronic HIV-1 infected compared with both healthy
      controls and long-term nonprogressors. We describe a novel mechanism whereby IL
      10 levels can be potentially modulated by changes to let-7 miRNAs. In HIV-1
      infection, the decrease in let-7 miRNAs may result in an increase in IL-10 from
      CD4(+) T cells and provide the virus with an important survival advantage by
      manipulating the host immune response.

PMID- 22586039
TI  - Chimeric antigen receptor T cells shape myeloid cell function within the tumor
      microenvironment through IFN-gamma and GM-CSF.
AB  - The infiltration of suppressive myeloid cells into the tumor microenvironment
      restrains anti-tumor immunity. However, cytokines may alter the function of
      myeloid lineage cells to support tumor rejection, regulating the balance between
      pro- and anti-tumor immunity. In this study, it is shown that effector cytokines
      secreted by adoptively transferred T cells expressing a chimeric Ag receptor
      (CAR) shape the function of myeloid cells to promote endogenous immunity and
      tumor destruction. Mice bearing the ovarian ID8 tumor were treated with T cells
      transduced with a chimeric NKG2D receptor. GM-CSF secreted by the adoptively
      transferred T cells recruited peripheral F4/80(lo)Ly-6C(+) myeloid cells to the
      tumor microenvironment in a CCR2-dependent fashion. T cell IFN-gamma and GM-CSF
      activated local, tumor-associated macrophages, decreased expression of regulatory
      factors, increased IL-12p40 production, and augmented Ag processing and
      presentation by host macrophages to Ag-specific T cells. In addition, T cell
      derived IFN-gamma, but not GM-CSF, induced the production of NO by F4/80(hi)
      macrophages and enhanced their lysis of tumor cells. The ability of CAR T cell
      therapy to eliminate tumor was moderately impaired when inducible NO synthase was
      inhibited and greatly impaired in the absence of peritoneal macrophages after
      depletion with clodronate encapsulated liposomes. This study demonstrates that
      the activation of host macrophages by CAR T cell-derived cytokines transformed
      the tumor microenvironment from immunosuppressive to immunostimulatory and
      contributed to inhibition of ovarian tumor growth.

PMID- 22586041
TI  - Cutting edge: Divergent cell-specific functions of MyD88 for inflammatory
      responses and organ injury in septic peritonitis.
AB  - Although global MyD88 deficiency attenuates lethal inflammation in sepsis, cell
      specific functions of MyD88 remain largely unknown. Using mice with selective
      expression of MyD88 in myeloid cells (Myd88(MYEL)), we show that, during
      polymicrobial septic peritonitis, both myeloid and nonmyeloid cells contribute to
      systemic inflammation, whereas myeloid cell MyD88 was sufficient to fully
      establish the peritoneal cytokine response. Importantly, Myd88(MYEL) mice
      developed markedly aggravated liver injury that was linked to impaired
      upregulation of cellular inhibitor of apoptosis protein 2 and an excessive
      production of TNF-alpha. Upregulation of inducible cAMP early repressor (ICER), a
      known transcriptional repressor of the Tnfa gene, was impaired in Myd88(MYEL)
      mice. Moreover, Myd88(MYEL) mice showed enhanced transcription of the Tnfa gene
      and an excessive production of CCL3, which is also negatively regulated by ICER,
      but they had normal levels of CXCL1, which is expressed in an ICER-independent
      manner. Together, these findings suggest a novel protective role for nonmyeloid
      cell MyD88 in attenuating liver injury during septic peritonitis.

PMID- 22586042
TI  - Herpes simplex virus type 2 infection of human epithelial cells induces CXCL9
      expression and CD4+ T cell migration via activation of p38-CCAAT/enhancer-binding
      protein-beta pathway.
AB  - Recruitment of CD4(+) T cells to infection areas after HSV-2 infection may be one
      of the mechanisms that account for increased HIV-1 sexual transmission.
      Lymphocytes recruited by chemokine CXCL9 are known to be important in control of
      HSV-2 infection in mice, although the underlying mechanism remains to be
      addressed. Based on our observation that CXCL9 expression is augmented in the
      cervical mucus of HSV-2-positive women, in this study we demonstrate that HSV-2
      infection directly induces CXCL9 expression in primary cervical epithelial cells
      and cell lines, the principal targets of HSV-2, at both mRNA and protein levels.
      Further studies reveal that the induction of CXCL9 expression by HSV-2 is
      dependent upon a binding site for C/EBP-beta within CXCL9 promoter sequence.
      Furthermore, CXCL9 expression is promoted at the transcriptional level through
      phosphorylating C/EBP-beta via p38 MAPK pathway, leading to binding of C/EBP-beta
      to the CXCL9 promoter. Chemotaxis assays indicate that upregulation of CXCL9
      expression at the protein level by HSV-2 infection enhances the migration of PBLs
      and CD4(+) T cells, whereas neutralization of CXCL9 or inhibition of p38-C/EBP
      beta pathway can significantly decrease the migration. Our data together
      demonstrate that HSV-2 induces CXCL9 expression in human cervical epithelial
      cells by activation of p38-C/EBP-beta pathway through promoting the binding of
      C/EBP-beta to CXCL9 promoter, which may recruit activated CD4(+) T cells to
      mucosal HSV-2 infection sites and potentially increase the risk of HIV-1 sexual
      transmission.

PMID- 22586043
TI  - Molecular testing in colorectal cancer: diagnosis of Lynch syndrome and
      personalized cancer medicine.
AB  - Currently, molecular testing in colorectal cancer (CRC) is aimed at detecting
      Lynch syndrome and predicting response to anti-epidermal growth factor receptor
      (EGFR) therapies. However, CRC is a complex disease, with at least 3 molecular
      pathways of carcinogenesis. The importance of the EGFR signaling pathway in
      colorectal carcinogenesis is underscored by the availability of anti-EGFR
      monoclonal antibodies for the treatment of some metastatic CRCs. Potentially,
      mutations in any of the genes in the EGFR signaling pathway may be associated
      with prognosis and may predict response to anti-EGFR or other targeted therapies.
      Although not currently the standard of care, molecular testing of CRCs is
      expanding to include mutational analysis of the genes in the EGFR pathway, in
      addition to more widely performed tests for identifying cancers with high
      microsatellite instability. Multiplex molecular prognostic panels for therapeutic
      decision making in stage II CRCs also represent expanding use of molecular
      testing for this common cancer.

PMID- 22586044
TI  - Absolute neutrophil counts from automated hematology instruments are accurate and
      precise even at very low levels.
AB  - Using 106 samples from patients with an absolute neutrophil count (ANC) less than
      2.0 * 10(9)/L, two 5-part differential hematology instruments (Sysmex XE-2100,
      Sysmex, Kobe, Japan, and Advia 2120i, Siemens Healthcare Diagnostics, Deerfield,
      IL), two 3-part differential hematology instruments (Sysmex K4500, Sysmex, and
      Advia 60, Siemens Healthcare Diagnostics), and an automated system for
      examination of microscopic slides (CellaVision DM96, CellaVision, Lund, Sweden)
      were compared with a flow cytometric (FCM) neutrophil count using monoclonal
      antibodies for cell classification. The precision and accuracy of the 5-part
      differential instrument ANC was very good at more than 0.1 * 10(9)/L, although a
      small systematic difference (10.3%) was found between the 2 instruments. The ANC
      of the 3-part differential instruments was less reliable, but the WBC count
      correlated very well with the WBC count from the 5-part differential instruments.
      Also, the neutrophil count from the CellaVision DM96 compared very well with FCM.
      When used in the correct laboratory setting, all of the evaluated instruments
      provide ANCs and WBCs with adequate accuracy and precision.

PMID- 22586045
TI  - Assessment of bone marrow fibrosis and angiogenesis in monitoring patients with
      multiple myeloma.
AB  - The aim of our study was to emphasize the importance of accurate and standardized
      techniques for detailed monitoring of the microenvironment in multiple myeloma
      (MM). Bone marrow fibrosis, angiogenesis, and plasma cell infiltrates in bone
      marrow biopsy (BMB) samples at the time of diagnosis and on completion of therapy
      were analyzed for 42 patients with newly diagnosed MM. Computerized image
      analysis was used for all slides stained with anti-CD138 and anti-CD34. The
      patients with fibrosis in pretreatment BMB samples had significantly higher
      microvessel density (MVD) and plasma cell infiltrates. In posttreatment BMB
      samples, nonresponders had a significantly higher frequency and grade of fibrosis
      and higher values of MVD, total vascular area, and plasma cell percentage. The
      overall survival of nonresponders and patients with increased marrow fibrosis in
      posttreatment BMB samples was significantly shorter. The obtained results confirm
      that complex morphologic examination of the bone marrow microenvironment during
      the monitoring of MM can provide better prognostic significance.

PMID- 22586046
TI  - Clinicopathologic analysis of peripheral T-cell lymphoma, follicular variant, and
      comparison with angioimmunoblastic T-cell lymphoma: Bcl-6 expression might affect
      progression between these disorders.
AB  - We examined clinicopathologic findings in 17 cases of peripheral T-cell lymphoma,
      follicular variant (f-PTCL), and compared these findings with angioimmunoblastic
      T-cell lymphoma (AITL) to determine whether they were identical to the spectrum
      of changes seen in AITL and how each of the findings in f-PTCL were related to
      the characteristics of AITL. Almost all f-PTCL cases showed pathologic
      characteristics of AITL and immunohistochemical positivities in lymphoma cells
      for CD4, CD10, Bcl-6, PD-1, and CXCL13. Except for pathologic characteristics,
      clinicopathologic findings in f-PTCL had few significant differences from AITL.
      The positive rate for Bcl-6 expression in neoplastic cells was significantly
      associated with the frequency of polymorphic infiltrates, vascular proliferation,
      B-immunoblasts, clear cells, Epstein-Barr virus-positive lymphocytes,
      hepatosplenomegaly, and skin rash. Our study confirmed the continuity between f
      PTCL and AITL. Moreover, Bcl-6 expression in f-PTCL was statistically associated
      with the characteristics of AITL.

PMID- 22586047
TI  - Extended use of serum free light chain as a biomarker in lymphoproliferative
      disorders: a comprehensive review.
AB  - Serum free light chain (sFLC) assays were shown to improve detection, management,
      and prognostication in plasma cell disorders. Recently, sFLC assays improved
      detection of M proteins when combined with standard methods of protein
      electrophoresis/immunofixation in patients with non-Hodgkin lymphoma/chronic
      lymphocytic leukemia (NHL/CLL). Incidence of abnormal sFLC ratio (sFLCr) varied
      from 0% to 36% and 29.7% to 59% in NHL and CLL, respectively. Increased sFLC
      levels or abnormal sFLCr predict shorter overall survival in early-stage CLL.
      Furthermore, abnormal sFLCr correlated with advanced disease stage and poorer
      outcome. In diffuse large B-cell lymphomas, increased sFLC was demonstrated as an
      independent, adverse prognostic factor for overall/event-free survival. Moreover,
      abnormal sFLCr can be a diagnostic tool in central nervous system lymphomas.
      Finally, the quantitative FLC assay has the potential to become a new, easily
      measured biomarker for predicting prognosis and enhanced detection in NHL/CLL. It
      may be used serially at follow-up evaluations to provide clues to relapse.

PMID- 22586048
TI  - Effect of carryover of clot activators on coagulation tests during phlebotomy.
AB  - We investigated the effect of clot activators carried over from the serum tube on
      major coagulation tests during phlebotomy. First, blood specimens from 30 normal
      subjects were mixed with small amounts of fluid containing clot activators, and
      their effects on various coagulation tests were determined. Only the value of
      fibrin monomer complex displayed a remarkable change when thrombin-containing
      fluid was added to the blood specimens. Subsequently, 100 paired blood specimens
      (taken from 75 healthy volunteers and 25 patients taking warfarin) were collected
      in coagulation tubes before and after the serum tube using standard phlebotomy
      procedures. Various coagulation tests were performed to determine the effect of
      contamination of thrombin-containing blood on coagulation parameters. Differences
      between the 2 tubes were minimal but significant for some of the coagulation
      tests. Therefore, we conclude that the effect of clot activators in the serum
      tube on coagulation tests is minimal when standard phlebotomy procedures are
      used.

PMID- 22586049
TI  - Recommendations for appropriate activated partial thromboplastin time reagent
      selection and utilization.
AB  - The activated partial thromboplastin time (aPTT) is widely used as a screening
      coagulation test and for monitoring unfractionated heparin therapy. Various
      commercial reagents are available, with different performance characteristics,
      particularly responsiveness to the lupus anticoagulant (LA). Because aPTT reagent
      selection significantly affects the interpretation of results, we reviewed
      College of American Pathologists proficiency testing data involving approximately
      4,000 coagulation laboratories, and conducted a survey of coagulation
      laboratories (n = 93) using The Fritsma Factor hemostasis Web site to determine
      the basis for aPTT reagent selection. The data demonstrate that for routine aPTT
      testing, most laboratories use reagents with high/moderate responsiveness to LA.
      Significant misunderstanding was apparent regarding the use of appropriate aPTT
      reagent for routine testing and LA identification. We recommend aPTT reagents
      with low LA responsiveness to screen for coagulation factor deficiencies and
      heparin monitoring, and suggest continued education of laboratory professionals
      and reagent manufacturers about appropriate aPTT reagent use.

PMID- 22586050
TI  - Protein C assay performance: an analysis of North American specialized
      coagulation laboratory association proficiency testing results.
AB  - To determine the performance and frequency of protein C reagents currently used
      by clinical laboratories, we analyzed North American Specialized Coagulation
      Laboratory Association (NASCOLA) protein C proficiency testing data from 6
      surveys conducted in 2009 and 2010 (2009-1 to 2009-3 and 2010-1 to 2010-3).
      Interlaboratory coefficients of variation (CV) for commonly used reagents on a
      survey with normal protein C ranged from 8% to 12% for antigenic assays, from 4%
      to 7% for chromogenic activity assays, and from 7% to 22% for clot-based activity
      assays. CVs for commonly used reagents on specimens with abnormal protein C
      ranged from 15% to 24% for antigenic, 4% to 11% for chromogenic, and 10% to 17%
      for clot-based assays (averaged across 3 surveys). Some reagents were used by
      relatively few laboratories and therefore additional study may be needed for
      those reagents. For all commonly used reagents, biases were usually small and
      often not statistically significant. All assessed reagents were clinically
      accurate, and were considered acceptable options for a specialized coagulation
      laboratory.

PMID- 22586051
TI  - A search for reliable molecular markers of prognosis in prostate cancer: a study
      of 240 cases.
AB  - Most prostate cancers are treated, although more than 80% remain clinically
      insignificant and fewer than 3% are fatal. This retrospective study of 240
      radical prostatectomy cases with comprehensive follow-up was a search for
      reliable markers of prostate cancer prognosis evaluable on biopsy specimens to
      enable minimization of unnecessary treatment, morbidity, and costs.
      Representative cancer and benign tissue from each prostatectomy specimen was made
      into tissue microarrays and stained with antibodies targeting 20 gene sequences.
      Traditional clinical and pathologic prognosticators and the 20 antibody stains
      were correlated with patient outcomes. By univariable analysis 4 of 20 antibodies
      (STMN1/stathmin 1, CYP4Z1/cytochrome p450-4z1, CDH1/E-cadherin, and Hey2),
      Gleason score, perineural invasion, and apical involvement were statistically
      significant outcome predictors for biopsy tissue. By multivariate analysis,
      Gleason score, Hey2, and CYP4Z1 were independently predictive. STMN1 and CDH1
      were not independent of Gleason score but remain useful because marker
      interpretation is objective and Gleason scores often differ for biopsy and
      prostatectomy specimens.

PMID- 22586052
TI  - Foxp3 expression patterns in microscopic colitides: a clinicopathologic study of
      69 patients.
AB  - Microscopic colitides, including lymphocytic (LC) and collagenous colitis (CC),
      are well-described pathologic conditions. An altered immune response is
      implicated in the pathogenesis of both entities. CD8+ T lymphocytes (CTLs)
      secrete interleukin 2 which stimulates proliferation of regulatory T cells
      (Tregs), and Tregs, in turn, inhibit CTLs, inducing cytotoxic tissue damage. In
      Tregs, Foxp3 regulates T-cell-related immune responses. The distribution of Tregs
      and CTLs in microscopic colitides has remained underexplored. To characterize
      differences in the distribution pattern of Foxp3 in biopsy specimens from
      patients with LC and CC, 71 colonic biopsy specimens from 69 consecutive patients
      were categorized into 1 of 3 diagnoses: no significant histopathologic
      abnormality (NSHPA), LC, or CC. Further immunohistochemical evaluation of all
      biopsy specimens was conducted using a panel of markers including CD8 and Foxp3.
      Our study demonstrated that CTL distribution pattern differences exist among
      these 2 colitides and that differences in the immunologic recruitment of Foxp3+
      Tregs in the colonic mucosa correlate with differences in the spectrum of
      morphologic changes seen in patients with either LC or CC.

PMID- 22586053
TI  - Differential diagnostic value of GPC3-CD34 combined staining in small liver
      nodules with diameter less than 3 cm.
AB  - The diagnostic value of combining glypican-3 (GPC3) and CD34 staining for small
      nodules in liver biopsy specimens has not been evaluated. In this study, 201 thin
      core biopsy specimens were assessed using GPC3 and CD34 immunochemical staining,
      including 33 cirrhotic regenerative nodules, 31 high-grade dysplastic nodules, 70
      hepatocellular carcinomas (HCCs) with nodules 3 cm or smaller, and 67 HCCs with
      nodules larger than 3 cm. The results showed that the accuracy of GPC3 staining
      (90.3%) among liver nodules 3 cm or smaller was better than its use among all
      nodules (P = .045). Furthermore, the positive expression rate of costaining was
      significantly greater than that observed for GPC3 or CD34 single staining (P <
      .001 and P = .002, respectively). These data demonstrate that GPC3 staining is
      more accurate for the diagnosis of HCC on thin-core biopsy specimens in nodules 3
      cm or smaller compared with its use in all nodules, while GPC3 and CD34
      costaining has better diagnostic value than does single staining.

PMID- 22586054
TI  - Tissue-sparing application of the newly proposed IASLC/ATS/ERS classification of
      adenocarcinoma of the lung shows practical diagnostic and prognostic impact.
AB  - The histologic subtype of non-small cell lung cancer (NSCLC) determines treatment
      strategies and the need for genetic analyses. Since most NSCLC are diagnosed on
      small biopsy or cytologic specimens, an accurate but tissue-sparing approach is
      necessary. To date, consensus for a general diagnostic algorithm is lacking. To
      test the diagnostic and clinical relevance of the recently published
      multidisciplinary guidelines by the International Association for the Study of
      Lung Cancer, American Thoracic Society, and European Respiratory Society, we
      examined 371 surgically resected NSCLCs brought into tissue microarray format.
      The antibody panel thyroid transcription factor-1 (TTF-1), p63, cytokeratin
      (CK)5/6, and CK7 is diagnostic for most cases (>94%). Faint/focal staining for
      CK7 is negligible for classificatory purposes. Grading adenocarcinomas according
      to histologic architecture is prognostically significant (median overall survival
      for well/moderate differentiation, 72.5 months; for poor differentiation, 38.5
      months; P = .019). Double stains combining the aforementioned nuclear and
      membranous markers are highly diagnostic for NSCLC, conserving tumor tissue for
      subsequent analyses.

PMID- 22586055
TI  - The dynamics of death in prostate cancer.
AB  - The hazard function provides the instantaneous probability of death (or other key
      end point) at various times after diagnosis. Unlike the survival curve, the
      hazard function illustrates graphically or through calculations when deaths are
      common or uncommon. In this study, hazard functions were derived for prostate
      cancer by using survival data on large numbers of patients with prostate cancer
      with data in the Surveillance, Epidemiology and End Results (SEER) database. The
      results demonstrate a form of prostate cancer that rapidly evolves to cause death
      within 5 years, and this form of tumor is only partly identified by routine
      prognostic variables such as serum prostate-specific antigen (PSA) level,
      histologic grade, and quantity of tumor. The results also validate the presence
      of a reservoir of nonfatal prostate cancers that have increased rapidly during
      the PSA era, and they demonstrate that the incidence of fatal prostate cancers
      has declined.

PMID- 22586056
TI  - Solitary fibrous tumor: is there a molecular relationship with cellular
      angiofibroma, spindle cell lipoma, and mammary-type myofibroblastoma?
AB  - Solitary fibrous tumor (SFT) is a mesenchymal tumor characterized by ovoid cells,
      branching blood vessels, stromal hyalinization, and CD34 immunoreactivity.
      Studies have shown loss of 13q in a group of morphologically similar entities,
      including cellular angiofibroma, mammary-type myofibroblastoma, and spindle cell
      lipoma. The histologic and immunophenotypic overlap between SFT and the latter
      group of tumors suggests that these tumors may be genetically linked. We tested a
      group of 40 SFTs to assess for loss of RB1 (13q14) by fluorescence in situ
      hybridization (FISH). All 38 SFTs with evaluable signals failed to show loss of
      RB1 (13q14) by FISH. All cases of cellular angiofibroma (1/1), spindle cell
      lipoma (6/6), and mammary-type myofibroblastoma (4/4), which were used as a
      control group, showed monoallelic or biallelic loss of RB1. The absence of RB1
      loss in SFTs suggests that they are not related to cellular angiofibroma, mammary
      type myofibroblastoma, or spindle cell lipoma.

PMID- 22586057
TI  - LMX1A as a prognostic marker in ovarian mucinous cystadenocarcinoma.
AB  - This study aimed to evaluate the relationship of LMX1A and osteopontin (OPN)
      expression with clinicopathologic parameters for the 4 most common ovarian
      surface epithelial carcinomas. Both biomarkers were investigated
      immunohistochemically using tissue microarrays of 249 specimens including 91
      serous cystadenocarcinomas, 56 mucinous cystadenocarcinomas, 64 endometrioid
      adenocarcinomas, 26 clear cell carcinomas, and 12 normal ovarian tissues. All 4
      carcinomas showed significant expression of LMX1A and OPN. In addition, higher
      immunostaining scores and percentage of cells stained for LMX1A in mucinous
      cystadenocarcinomas correlated with T stage, American Joint Committee on Cancer
      clinical stage, poorer tumor differentiation, and poorer survival rate. In serous
      cystadenocarcinoma, higher percentage of staining for OPN and higher intensity or
      immunostaining scores for LMX1A correlated with poorer tumor differentiation.
      Thus, the expression of LMX1A may be an independent prognostic risk factor in
      mucinous cystadenocarcinoma and a helpful marker in evaluating this tumor's
      aggressiveness.

PMID- 22586058
TI  - Ectopic expression of TIM-3 in lung cancers: a potential independent prognostic
      factor for patients with NSCLC.
AB  - T-cell immunoglobulin- and mucin domain-3-containing molecule 3 (TIM-3) is a
      membrane protein expressed in various kinds of immune cells and plays a pivotal
      role in immune regulation. Recently, TIM-3 was reported to be expressed
      aberrantly in melanoma cells, contributing to the low adhesion ability of tumor
      cells and promoting the survival of melanoma cells. We investigated TIM-3
      expression in non-small cell lung cancers (NSCLCs), and further analyzed whether
      the aberrant expression of TIM-3 is related to the prognosis for patients with
      lung cancer. Tumor tissue samples from 30 patients with NSCLC were involved.
      Results of immunohistochemical analysis showed that TIM-3 stained positive on
      tumor cells in 86.7% (26/30) patients with primary NSCLC. The TIM-3 expression in
      NSCLC tumor cells was correlated with histologic type and pathologic T
      classification of the disease (P < .05). More importantly, patients with TIM-3
      positive tumor cells had a significantly shorter survival time than those with
      TIM-3-negative tumors. Multivariate analysis demonstrated the significant role of
      TIM-3 expression in tumor cells as an independent prognostic factor for patients
      with NSCLC (relative risk, 4.481; 95% confidence interval, 1.790-11.22; P =
      .0005). Our results suggest that the ectopic expression of TIM-3 in tumor cells
      may be a potential, independent prognostic factor for patients with NSCLC.

PMID- 22586060
TI  - ATHENA trial CIN 2+ cervical biopsy misclassifications raise questions.

PMID- 22586061
TI  - Brain-to-brain turnaround loop.

PMID- 22586062
TI  - Immunophenotypic stability of CD200 expression in plasma cell myeloma.

PMID- 22586063
TI  - Transcriptional signatures of Ral GTPase are associated with aggressive
      clinicopathologic characteristics in human cancer.
AB  - RalA and RalB are small GTPases that support malignant development and
      progression in experimental models of bladder, prostate, and squamous cancer.
      However, demonstration of their clinical relevance in human tumors remains
      lacking. Here, we developed tools to evaluate Ral protein expression, activation,
      and transcriptional output and evaluated their association with clinicopathologic
      parameters in common human tumor types. To evaluate the relevance of Ral
      activation and transcriptional output, we correlated RalA and RalB activation
      with the mutational status of key human bladder cancer genes. We also identified
      and evaluated a transcriptional signature of genes that correlates with depletion
      of RalA and RalB in vivo. The Ral transcriptional signature score, but not
      protein expression as evaluated by immunohistochemistry, predicted disease stage,
      progression to muscle invasion, and survival in human bladder cancers and
      metastatic and stem cell phenotypes in bladder cancer models. In prostate cancer,
      the Ral transcriptional signature score was associated with seminal vesicle
      invasion, androgen-independent progression, and reduced survival. In squamous
      cell carcinoma, this score was decreased in cancer tissues compared with normal
      mucosa, validating the experimental findings that Ral acts as a tumor suppressor
      in this tumor type. Together, our findings show the clinical relevance of Ral in
      human cancer and provide a rationale for the development of Ral-directed
      therapies.

PMID- 22586064
TI  - Fra-1 promotes breast cancer chemosensitivity by driving cancer stem cells from
      dormancy.
AB  - Fra-1 is a member of the Fos transcription factor family that is highly expressed
      in multiple cancers, playing important roles in transformation, proliferation,
      and metastasis. In this study, we observed an inverse correlation between the
      expression of Fra-1 in human stage II breast cancer tissues and the corresponding
      level of clinical chemoresistance. Extending these findings in vitro, we found
      that knockdown of Fra-1 in breast tumor cells was sufficient to confer resistance
      to doxorubicin and cyclophosphamide, whereas enhanced Fra-1 expression could
      render these cells chemosensitive. The tumor cell side population, which is
      enriched for cancer stem cells, was found to be associated with chemoresistance.
      Increased side population fractions were detected among tumor cell lines
      subjected to Fra-1 knockdown. In contrast, enhanced expression of Fra-1 was
      correlated with a decreased side population fraction, and significantly, this
      finding was recapitulated in vivo, where tumors with enhanced expression of Fra-1
      were found to have blunted growth. Tumor cells subjected to Fra-1 knockdown grew
      faster and were larger in size. Taken together, our findings suggest that Fra-1
      may be an important prognostic marker for breast cancer therapy.

PMID- 22586065
TI  - Chk2 phosphorylation of survivin-DeltaEx3 contributes to a DNA damage-sensing
      checkpoint in cancer.
AB  - Survivin is an oncogene that functions in cancer cell cytoprotection and mitosis.
      Here we report that differential expression in cancer cells of a C-terminal
      splice variant of survivin, termed survivin-DeltaEx3, is tightly associated with
      aggressive disease and markers of unfavorable prognosis. In contrast to other
      survivin variants, survivin-DeltaEx3 localized exclusively to nuclei in tumor
      cells and was phosphorylated at multiple residues by the checkpoint kinase Chk2
      during DNA damage. Mutagenesis of the Chk2 phosphorylation sites enhanced the
      stability of survivin-DeltaEx3 in tumor cells, inhibited the expression of
      phosphorylated H2AX (gammaH2AX) in response to double-strand DNA breaks, and
      impaired growth after DNA damage. DNA damage induced Chk2 phosphorylation,
      stabilization of p53, induction of the cyclin-dependent kinase inhibitor p21, and
      homologous recombination-induced repair were not affected. In vivo, active Chk2
      was detected at the earliest stages of the colorectal adenoma-to-carcinoma
      transition, persisted in advanced tumors, and correlated with increased survivin
      expression. Together, our findings suggest that Chk2-mediated phosphorylation of
      survivin-DeltaEx3 contributes to a DNA damage-sensing checkpoint that may affect
      cancer cell sensitivity to genotoxic therapies.

PMID- 22586066
TI  - Corallopyronin A specifically targets and depletes essential obligate Wolbachia
      endobacteria from filarial nematodes in vivo.
AB  - Doxycycline and rifampicin deplete essential Wolbachia from filarial nematodes
      that cause lymphatic filariasis or onchocerciasis, resulting in blocked worm
      development and death. However, doxycycline is contraindicated for children and
      pregnant/breastfeeding women, as is rifampicin in the latter group with the
      additional specter of possible resistance development in Mycobacterium spp. Novel
      antibiotics with a narrower spectrum would aid in eliminating filarial diseases.
      Corallococcus coralloides synthesizes corallopyronin A, a noncompetitive
      inhibitor of RNA polymerase ineffective against Mycobacterium spp. Corallopyronin
      A depleted Wolbachia from infected insect cells (1.89 Thus the antibiotic is
      effective against intracellular bacteria despite the many intervening surfaces
      (blood vessels, pleura, worm cuticle) and membranes (worm cell, vesicle,
      Wolbachia inner and outer membranes). Corallopyronin A is an antibiotic to
      develop further for filariasis elimination without concern for cross-resistance
      development in tuberculosis.

PMID- 22586067
TI  - Feature engineering combined with machine learning and rule-based methods for
      structured information extraction from narrative clinical discharge summaries.
AB  - OBJECTIVE: A system that translates narrative text in the medical domain into
      structured representation is in great demand. The system performs three sub
      tasks: concept extraction, assertion classification, and relation identification.
      DESIGN: The overall system consists of five steps: (1) pre-processing sentences,
      (2) marking noun phrases (NPs) and adjective phrases (APs), (3) extracting
      concepts that use a dosage-unit dictionary to dynamically switch two models based
      on Conditional Random Fields (CRF), (4) classifying assertions based on voting of
      five classifiers, and (5) identifying relations using normalized sentences with a
      set of effective discriminating features. MEASUREMENTS: Macro-averaged and micro
      averaged precision, recall and F-measure were used to evaluate results. RESULTS:
      The performance is competitive with the state-of-the-art systems with micro
      averaged F-measure of 0.8489 for concept extraction, 0.9392 for assertion
      classification and 0.7326 for relation identification. CONCLUSIONS: The system
      exploits an array of common features and achieves state-of-the-art performance.
      Prudent feature engineering sets the foundation of our systems. In concept
      extraction, we demonstrated that switching models, one of which is especially
      designed for telegraphic sentences, improved extraction of the treatment concept
      significantly. In assertion classification, a set of features derived from a rule
      based classifier were proven to be effective for the classes such as conditional
      and possible. These classes would suffer from data scarcity in conventional
      machine-learning methods. In relation identification, we use two-staged
      architecture, the second of which applies pairwise classifiers to possible
      candidate classes. This architecture significantly improves performance.

PMID- 22586069
TI  - Perspectives on the convergent evolution of tetrapod salt glands.
AB  - Since their discovery in 1958, the function of specialized salt-secreting glands
      in tetrapods has been studied in great detail, and such studies continue to
      contribute to a general understanding of transport mechanisms of epithelial water
      and ions. Interestingly, during that same time period, there have been only few
      attempts to understand the convergent evolution of this tissue, likely as a
      result of the paucity of taxonomic, embryological, and molecular data available.
      In this review, we synthesize the available data regarding the distribution of
      salt glands across extant and extinct tetrapod lineages and the anatomical
      position of the salt gland in each taxon. Further, we use these data to develop
      hypotheses about the various factors that have influenced the convergent
      evolution of salt glands across taxa with special focus on the variation in the
      anatomical position of the glands and on the molecular mechanisms that may have
      facilitated the development of a salt gland by co-option of a nonsalt-secreting
      ancestral gland. It is our hope that this review will stimulate renewed interest
      in the topic of the convergent evolution of salt glands and inspire future
      empirical studies aimed at evaluating the hypotheses we lay out herein.

PMID- 22586068
TI  - Assessing the influence of traffic-related air pollution on risk of term low
      birth weight on the basis of land-use-based regression models and measures of air
      toxics.
AB  - Few studies have examined associations of birth outcomes with toxic air
      pollutants (air toxics) in traffic exhaust. This study included 8,181 term low
      birth weight (LBW) children and 370,922 term normal-weight children born between
      January 1, 1995, and December 31, 2006, to women residing within 5 miles (8 km)
      of an air toxics monitoring station in Los Angeles County, California.
      Additionally, land-use-based regression (LUR)-modeled estimates of levels of
      nitric oxide, nitrogen dioxide, and nitrogen oxides were used to assess the
      influence of small-area variations in traffic pollution. The authors examined
      associations with term LBW (>=37 weeks' completed gestation and birth weight
      <2,500 g) using logistic regression adjusted for maternal age, race/ethnicity,
      education, parity, infant gestational age, and gestational age squared. Odds of
      term LBW increased 2%-5% (95% confidence intervals ranged from 1.00 to 1.09) per
      interquartile-range increase in LUR-modeled estimates and monitoring-based air
      toxics exposure estimates in the entire pregnancy, the third trimester, and the
      last month of pregnancy. Models stratified by monitoring station (to investigate
      air toxics associations based solely on temporal variations) resulted in 2%-5%
      increased odds per interquartile-range increase in third-trimester benzene,
      toluene, ethyl benzene, and xylene exposures, with some confidence intervals
      containing the null value. This analysis highlights the importance of both
      spatial and temporal contributions to air pollution in epidemiologic birth
      outcome studies.

PMID- 22586070
TI  - Morphological analysis of systolic anterior motion after mitral valve repair.
AB  - OBJECTIVES: The systolic anterior motion (SAM) of mitral valves occurs at a
      certain rate despite the introduction of several preventive procedures. The
      purpose of this study was to investigate its mechanism by analysing the change in
      mitral valve morphology associated with operative procedures. METHODS: Components
      of mitral valves were measured before and after operative procedures by
      transoesophageal echocardiography in 179 patients who underwent mitral valve
      repair. Comparisons were made between 15 patients with SAM (SAM group) and 164
      patients without SAM (non-SAM group). RESULTS: Morphological analysis in all the
      studied patients revealed that operative procedures shifted the coaptation point
      towards the left ventricular outflow tract by 6.9 mm and increased the extra
      portion of anterior leaflet that extended beyond the coaptation point by 5.4 mm.
      These changes were enhanced in the SAM group. Intergroup comparison revealed that
      there were no differences in the preoperative mitral valve morphologies between
      the two groups. After operative procedures, however, the SAM group showed smaller
      annular diameter and smaller coapted anterior/posterior length ratio compared
      with the non-SAM group. CONCLUSIONS: The results of this study show that
      operative procedures might modify the morphology of mitral valves susceptible to
      developing SAM. Postoperative smaller annular diameter and anterior shift of
      coaptation point were considered to contribute to the development of SAM.

PMID- 22586071
TI  - Ergonomics in thoracoscopic surgery: results of a survey among thoracic surgeons.
AB  - OBJECTIVES: The frequent and prolonged use of thoracoscopic equipment raises
      ergonomic risks which may cause physical distress. We aimed to determine the
      relationship between ergonomic problems encountered in thoracoscopic surgery and
      physical distress among thoracic surgeons. METHODS: An online questionnaire which
      investigated personal factors, product factors, interaction factors and physical
      discomfort was sent to all members of the European Society of Thoracic Surgeons
      (ESTS). RESULTS: Of the respondents, 2.4% indicated that a one arm's length
      should be the optimal distance between the surgeon and the monitor. Only 2.4%
      indicated that the monitor should be positioned below the eye level of the
      surgeon. Most of the respondents agreed, partially to fully, that they
      experienced neck discomfort because of inappropriate monitor height, bad monitor
      position and bad table height. Most respondents experienced numb fingers and
      shoulder discomfort due to instrument manipulation. Most of the respondents
      (77.1%) experienced muscle fatigue to some extent due to a static posture during
      thoracoscopic surgery. The majority of respondents (81.9, 76.3 and 83.2%
      respectively) indicated that they had varying degrees of discomfort mainly in the
      neck, shoulder and back. Some 94.4% of respondents were unaware of any guidelines
      concerning table height, monitor and instrument placement for endoscopic surgery.
      CONCLUSIONS: Most thoracic surgeons in Europe are unaware of ergonomic guidelines
      and do not practise them, hence they suffer varying degrees of physical
      discomfort arising from ergonomic issues.

PMID- 22586072
TI  - Modeling of the growth kinetics of occult breast tumors: role in interpretation
      of studies of prevention and menopausal hormone therapy.
AB  - BACKGROUND: Autopsy studies report a reservoir of small, occult, undiagnosed
      breast cancers in up to 15.6% of women dying from unrelated causes. The effective
      doubling times (EDT) of these occult neoplasms range from 70 to 350 days and
      mammographic detection threshold diameters from 0.88 to 1.66 cm. Modeling of the
      biologic behavior of these occult tumors facilitates interpretation of tamoxifen
      breast cancer prevention and menopausal hormone therapy studies. METHODS: We used
      iterative and mathematical techniques to develop a model of occult tumor growth
      (OTG) whose parameters included prevalence, EDT, and detection threshold. The
      model was validated by comparing predicted with observed incidence of breast
      cancer in several populations. RESULTS: Iterative analysis identified a 200-day
      EDT, 7% prevalence and 1.16 cm detection threshold as optimal parameters for an
      OTG model as judged by comparison with Surveillance Epidemiology and End Results
      (SEER) population incidence rates in the United States. We validated the model by
      comparing predicted incidence rates with those observed in five separate
      population databases, in three long-term contralateral breast cancer detection
      studies, and with data from a computer-simulated tumor growth (CSTG) model. Our
      model strongly suggests that breast cancer prevention with anti-estrogens or
      aromatase inhibitors represents early treatment not prevention. In addition,
      menopausal hormone therapy does not primarily induce de novo tumors but promotes
      the growth of occult lesions. CONCLUSIONS: Our OGTG model suggests that occult,
      undiagnosed tumors are prevalent, grow slowly, and are the biologic targets of
      anti-estrogen therapy for prevention and hormone therapy for menopausal women.

PMID- 22586073
TI  - Ultrafast photodriven intramolecular electron transfer from an iridium-based
      water-oxidation catalyst to perylene diimide derivatives.
AB  - Photodriving the activity of water-oxidation catalysts is a critical step toward
      generating fuel from sunlight. The design of a system with optimal energetics and
      kinetics requires a mechanistic understanding of the single-electron transfer
      events in catalyst activation. To this end, we report here the synthesis and
      photophysical characterization of two covalently bound chromophore-catalyst
      electron transfer dyads, in which the dyes are derivatives of the strong
      photooxidant perylene-3,4:9,10-bis(dicarboximide) (PDI) and the molecular
      catalyst is the Cp*Ir(ppy)Cl metal complex, where ppy = 2-phenylpyridine.
      Photoexcitation of the PDI in each dyad results in reduction of the chromophore
      to PDI(*-) in less than 10 ps, a process that outcompetes any generation of
      (3*)PDI by spin-orbit-induced intersystem crossing. Biexponential charge
      recombination largely to the PDI-Ir(III) ground state is suggestive of multiple
      populations of the PDI(*-)-Ir(IV) ion-pair, whose relative abundance varies with
      solvent polarity. Electrochemical studies of the dyads show strong irreversible
      oxidation current similar to that seen for model catalysts, indicating that the
      catalytic integrity of the metal complex is maintained upon attachment to the
      high molecular weight photosensitizer.

PMID- 22586074
TI  - Instant spectral assignment for advanced decision tree-driven mass spectrometry.
AB  - We have developed and implemented a sequence identification algorithm (inSeq)
      that processes tandem mass spectra in real-time using the mass spectrometer's
      (MS) onboard processors. The inSeq algorithm relies on accurate mass tandem MS
      data for swift spectral matching with high accuracy. The instant spectral
      processing technology takes ~16 ms to execute and provides information to enable
      autonomous, real-time decision making by the MS system. Using inSeq and its
      advanced decision tree logic, we demonstrate (i) real-time prediction of peptide
      elution windows en masse (~3 min width, 3,000 targets), (ii) significant
      improvement of quantitative precision and accuracy (~3x boost in detected protein
      differences), and (iii) boosted rates of posttranslation modification site
      localization (90% agreement in real-time vs. offline localization rate and an
      approximate 25% gain in localized sites). The decision tree logic enabled by
      inSeq promises to circumvent problems with the conventional data-dependent
      acquisition paradigm and provides a direct route to streamlined and expedient
      targeted protein analysis.

PMID- 22586075
TI  - Photoprotection in a purple phototrophic bacterium mediated by oxygen-dependent
      alteration of carotenoid excited-state properties.
AB  - Carotenoids are known to offer protection against the potentially damaging
      combination of light and oxygen encountered by purple phototrophic bacteria, but
      the efficiency of such protection depends on the type of carotenoid. Rhodobacter
      sphaeroides synthesizes spheroidene as the main carotenoid under anaerobic
      conditions whereas, in the presence of oxygen, the enzyme spheroidene
      monooxygenase catalyses the incorporation of a keto group forming spheroidenone.
      We performed ultrafast transient absorption spectroscopy on membranes containing
      reaction center-light-harvesting 1-PufX (RC-LH1-PufX) complexes and showed that
      when oxygen is present the incorporation of the keto group into spheroidene,
      forming spheroidenone, reconfigures the energy transfer pathway in the LH1, but
      not the LH2, antenna. The spheroidene/spheroidenone transition acts as a
      molecular switch that is suggested to twist spheroidenone into an s-trans
      configuration increasing its conjugation length and lowering the energy of the
      lowest triplet state so it can act as an effective quencher of singlet oxygen.
      The other consequence of converting carotenoids in RC-LH1-PufX complexes is that
      S(2)/S(1)/triplet pathways for spheroidene is replaced with a new pathway for
      spheroidenone involving an activated intramolecular charge-transfer (ICT) state.
      This strategy for RC-LH1-PufX-spheroidenone complexes maintains the light
      harvesting cross-section of the antenna by opening an active, ultrafast S(1)/ICT
      channel for energy transfer to LH1 Bchls while optimizing the triplet energy for
      singlet oxygen quenching. We propose that spheroidene/spheroidenone switching
      represents a simple and effective photoprotective mechanism of likely importance
      for phototrophic bacteria that encounter light and oxygen.

PMID- 22586076
TI  - Real-time analysis and selection of methylated DNA by fluorescence-activated
      single molecule sorting in a nanofluidic channel.
AB  - Epigenetic modifications, such as DNA and histone methylation, are responsible
      for regulatory pathways that affect disease. Current epigenetic analyses use
      bisulfite conversion to identify DNA methylation and chromatin
      immunoprecipitation to collect molecules bearing a specific histone modification.
      In this work, we present a proof-of-principle demonstration for a new method
      using a nanofluidic device that combines real-time detection and automated
      sorting of individual molecules based on their epigenetic state. This device
      evaluates the fluorescence from labeled epigenetic modifications to actuate
      sorting. This technology has demonstrated up to 98% accuracy in molecule sorting
      and has achieved postsorting sample recovery on femtogram quantities of genetic
      material. We have applied it to sort methylated DNA molecules using simultaneous,
      multicolor fluorescence to identify methyl binding domain protein-1 (MBD1) bound
      to full-duplex DNA. The functionality enabled by this nanofluidic platform now
      provides a workflow for color-multiplexed detection, sorting, and recovery of
      single molecules toward subsequent DNA sequencing.

PMID- 22586077
TI  - Dermatophytic defensin with antiinfective potential.
AB  - Fungi are a newly emerging source of peptide antibiotics with therapeutic
      potential. Here, we report 17 new fungal defensin-like peptide (fDLP) genes and
      the detailed characterization of a corresponding synthetic fDLP (micasin) from a
      dermatophyte in terms of its structure, activity and therapeutic potential. NMR
      analysis showed that synthetic micasin adopts a "hallmark" cysteine-stabilized
      alpha-helical and beta-sheet fold. It was active on both gram-positive and gram
      negative bacteria, and importantly it killed two clinical isolates of methicillin
      resistant Staphylococcus aureus and the opportunistic pathogen Pseudomonas
      aeruginosa at low micromolar concentrations. Micasin killed approximately 100% of
      treated bacteria within 3 h through a membrane nondisruptive mechanism of action,
      and showed extremely low hemolysis and high serum stability. Consistent with
      these functional properties, micasin increases survival in mice infected by the
      pathogenic bacteria in a peritonitis model. Our work represents a valuable
      approach to explore novel peptide antibiotics from a large resource of fungal
      genomes.

PMID- 22586078
TI  - Superpenetration optical microscopy by iterative multiphoton adaptive
      compensation technique.
AB  - Biological tissues are rarely transparent, presenting major challenges for deep
      tissue optical microscopy. The achievable imaging depth is fundamentally limited
      by wavefront distortions caused by aberration and random scattering. Here, we
      report an iterative wavefront compensation technique that takes advantage of the
      nonlinearity of multiphoton signals to determine and compensate for these
      distortions and to focus light inside deep tissues. Different from conventional
      adaptive optics methods, this technique can rapidly measure highly complicated
      wavefront distortions encountered in deep tissue imaging and provide
      compensations for not only aberration but random scattering. The technique is
      tested with a variety of highly heterogeneous biological samples including mouse
      brain tissue, skull, and lymph nodes. We show that high quality three-dimensional
      imaging can be realized at depths beyond the reach of conventional multiphoton
      microscopy and adaptive optics methods, albeit over restricted distances for a
      given correction. Moreover, the required laser excitation power can be greatly
      reduced in deep tissues, deviating from the power requirement of ballistic light
      excitation and thus significantly reducing photo damage to the biological tissue.

PMID- 22586079
TI  - Fe2+ binds iron responsive element-RNA, selectively changing protein-binding
      affinities and regulating mRNA repression and activation.
AB  - Iron increases synthesis rates of proteins encoded in iron-responsive element
      (IRE)-mRNAs; metabolic iron ("free," "labile") is Fe(2+). The noncoding IRE-RNA
      structure, approximately 30 nt, folds into a stem loop to control synthesis of
      proteins in iron trafficking, cell cycling, and nervous system function. IRE-RNA
      riboregulators bind specifically to iron-regulatory proteins (IRP) proteins,
      inhibiting ribosome binding. Deletion of the IRE-RNA from an mRNA decreases both
      IRP binding and IRP-independent protein synthesis, indicating effects of other
      "factors." Current models of IRE-mRNA regulation, emphasizing iron-dependent
      degradation/modification of IRP, lack answers about how iron increases IRE
      RNA/IRP protein dissociation or how IRE-RNA, after IRP dissociation, influences
      protein synthesis rates. However, we observed Fe(2+) (anaerobic) or Mn(2+)
      selectively increase the IRE-RNA/IRP K(D). Here we show: (i) Fe(2+) binds to the
      IRE-RNA, altering its conformation (by 2-aminopurine fluorescence and ethidium
      bromide displacement); (ii) metal ions increase translation of IRE-mRNA in vitro;
      (iii) eukaryotic initiation factor (eIF)4F binds specifically with high affinity
      to IRE-RNA; (iv) Fe(2+) increased eIF4F/IRE-RNA binding, which outcompetes IRP
      binding; (v) exogenous eIF4F rescued metal-dependent IRE-RNA translation in eIF4F
      depeleted extracts. The regulation by metabolic iron binding to IRE-RNA to
      decrease inhibitor protein (IRP) binding and increase activator protein (eIF4F)
      binding identifies IRE-RNA as a riboregulator.

PMID- 22586080
TI  - Closed-form density-based framework for automatic detection of cellular
      morphology changes.
AB  - A primary method for studying cellular function is to examine cell morphology
      after a given manipulation. Fluorescent markers attached to
      proteins/intracellular structures of interest in conjunction with 3D fluorescent
      microscopy are frequently exploited for functional analysis. Despite the central
      role of morphology comparisons in cell biological approaches, few statistical
      tools are available that allow biological scientists without a high level of
      statistical training to quantify the similarity or difference of fluorescent
      images containing multifactorial information. We transform intracellular
      structures into kernels and develop a multivariate two-sample test that is
      nonparametric and asymptotically normal to directly and quantitatively compare
      cellular morphologies. The asymptotic normality bypasses the computationally
      intensive calculations used by the usual resampling techniques to compute the P
      value. Because all parameters required for the statistical test are estimated
      directly from the data, it does not require any subjective decisions. Thus, we
      provide a black-box method for unbiased, automated comparison of cell morphology.
      We validate the performance of our test statistic for finite synthetic samples
      and experimental data. Employing our test for the comparison of the morphology of
      intracellular multivesicular bodies, we detect changes in their distribution
      after disruption of the cellular microtubule cytoskeleton with high statistical
      significance in fixed samples and live cell analysis. These results demonstrate
      that density-based comparison of multivariate image information is a powerful
      tool for automated detection of cell morphology changes. Moreover, the underlying
      mathematics of our test statistic is a general technique, which can be applied in
      situations where two data samples are compared.

PMID- 22586081
TI  - Fluorescence lifetime snapshots reveal two rapidly reversible mechanisms of
      photoprotection in live cells of Chlamydomonas reinhardtii.
AB  - Photosynthetic organisms avoid photodamage to photosystem II (PSII) in variable
      light conditions via a suite of photoprotective mechanisms called
      nonphotochemical quenching (NPQ), in which excess absorbed light is dissipated
      harmlessly. To quantify the contributions of different quenching mechanisms to
      NPQ, we have devised a technique to measure the changes in chlorophyll
      fluorescence lifetime as photosynthetic organisms adapt to varying light
      conditions. We applied this technique to measure the fluorescence lifetimes
      responsible for the predominant, rapidly reversible component of NPQ, qE, in
      living cells of Chlamydomonas reinhardtii. Application of high light to dark
      adapted cells of C. reinhardtii led to an increase in the amplitudes of 65 ps and
      305 ps chlorophyll fluorescence lifetime components that was reversed after the
      high light was turned off. Removal of the pH gradient across the thylakoid
      membrane linked the changes in the amplitudes of the two components to qE
      quenching. The rise times of the amplitudes of the two components were
      significantly different, suggesting that the changes are due to two different qE
      mechanisms. We tentatively suggest that the changes in the 65 ps component are
      due to charge-transfer quenching in the minor light-harvesting complexes and that
      the changes in the 305 ps component are due to aggregated light-harvesting
      complex II trimers that have detached from PSII. We anticipate that this
      technique will be useful for resolving the various mechanisms of NPQ and for
      quantifying the timescales associated with these mechanisms.

PMID- 22586082
TI  - alphaE-catenin is an autoinhibited molecule that coactivates vinculin.
AB  - alphaE-catenin, an essential component of the adherens junction, interacts with
      the classical cadherin-beta-catenin complex and with F-actin, but its precise
      role is unknown. alphaE-catenin also binds to the F-actin-binding protein
      vinculin, which also appears to be important in junction assembly. Vinculin and
      alphaE-catenin are homologs that contain a series of helical bundle domains, D1
      D5. We mapped the vinculin-binding site to a sequence in D3a comprising the
      central two helices of a four-helix bundle. The crystal structure of this peptide
      motif bound to vinculin D1 shows that the two helices adopt a parallel, colinear
      arrangement suggesting that the alphaE-catenin D3a bundle must unfold in order to
      bind vinculin. We show that alphaE-catenin D3 binds strongly to vinculin, whereas
      larger fragments and full-length alphaE-catenin bind approximately 1,000-fold
      more weakly. Thus, intramolecular interactions within alphaE-catenin inhibit
      binding to vinculin. The actin-binding activity of vinculin is inhibited by an
      intramolecular interaction between the head (D1-D4) and the actin-binding D5
      tail. In the absence of F-actin, there is no detectable binding of alphaE-catenin
      D3 to full-length vinculin; however, alphaE-catenin D3 promotes binding of
      vinculin to F-actin whereas full-length alphaE-catenin does not. These findings
      support the combinatorial or "coincidence" model of activation in which binding
      of high-affinity proteins to the vinculin head and tail is required to shift the
      conformational equilibrium of vinculin from a closed, autoinhibited state to an
      open, stable F-actin-binding state. The data also imply that alphaE-catenin must
      be activated in order to bind to vinculin.

PMID- 22586083
TI  - 2-Hydroxyoleate, a nontoxic membrane binding anticancer drug, induces glioma cell
      differentiation and autophagy.
AB  - Despite recent advances in the development of new cancer therapies, the treatment
      options for glioma remain limited, and the survival rate of patients has changed
      little over the past three decades. Here, we show that 2-hydroxyoleic acid
      (2OHOA) induces differentiation and autophagy of human glioma cells. Compared to
      the current reference drug for this condition, temozolomide (TMZ), 2OHOA combated
      glioma more efficiently and, unlike TMZ, tumor relapse was not observed following
      2OHOA treatment. The novel mechanism of action of 2OHOA is associated with
      important changes in membrane-lipid composition, primarily a recovery of
      sphingomyelin (SM) levels, which is markedly low in glioma cells before
      treatment. Parallel to membrane-lipid regulation, treatment with 2OHOA induced a
      dramatic translocation of Ras from the membrane to the cytoplasm, which inhibited
      the MAP kinase pathway, reduced activity of the PI3K/Akt pathway, and
      downregulated Cyclin D-CDK4/6 proteins followed by hypophosphorylation of the
      retinoblastoma protein (RB). These regulatory effects were associated with
      induction of glioma cell differentiation into mature glial cells followed by
      autophagic cell death. Given its high efficacy, low toxicity, ease of oral
      administration, and good distribution to the brain, 2OHOA constitutes a new and
      potentially valuable therapeutic tool for glioma patients.

PMID- 22586084
TI  - Allosteric pathways in imidazole glycerol phosphate synthase.
AB  - Protein allosteric pathways are investigated in the imidazole glycerol phosphate
      synthase heterodimer in an effort to elucidate how the effector (PRFAR, N'-[(5'
      phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamide ribonucleotide)
      activates glutaminase catalysis at a distance of 25 A from the glutamine-binding
      site. We apply solution NMR techniques and community analysis of dynamical
      networks, based on mutual information of correlated protein motions in the active
      and inactive enzymes. We find evidence that the allosteric pathways in the PRFAR
      bound enzyme involve conserved residues that correlate motion of the PRFAR
      binding loop to motion at the protein-protein interface, and ultimately at the
      glutaminase active site. The imidazole glycerol phosphate synthase bienzyme is an
      important branch point for the histidine and nucleotide biosynthetic pathways and
      represents a potential therapeutic target against microbes. The proposed
      allosteric mechanism and the underlying allosteric pathways provide fundamental
      insights for the design of new allosteric drugs and/or alternative herbicides.

PMID- 22586085
TI  - Structure, function and inhibition of the two- and three-domain 4Fe-4S IspG
      proteins.
AB  - IspG is a 4Fe4S protein involved in isoprenoid biosynthesis. Most bacterial IspGs
      contain two domains: a TIM barrel (A) and a 4Fe4S domain (B), but in plants and
      malaria parasites, there is a large insert domain (A*) whose structure and
      function are unknown. We show that bacterial IspGs function in solution as
      (AB)(2) dimers and that mutations in either both A or both B domains block
      activity. Chimeras harboring an A-mutation in one chain and a B-mutation in the
      other have 50% of the activity seen in wild-type protein, because there is still
      one catalytically active AB domain. However, a plant IspG functions as an AA*B
      monomer. We propose, using computational modeling and electron microscopy, that
      the A* insert domain has a TIM barrel structure that interacts with the A domain.
      This structural arrangement enables the A and B domains to interact in a "cup and
      ball" manner during catalysis, just as in the bacterial systems. EPR/HYSCORE
      spectra of reaction intermediate, product, and inhibitor ligands bound to both
      two and three domain proteins are identical, indicating the same local electronic
      structure, and computational docking indicates these ligands bridge both A and B
      domains. Overall, the results are of broad general interest because they indicate
      the insert domain in three-domain IspGs is a second TIM barrel that plays a
      structural role and that the pattern of inhibition of both two and three domain
      proteins are the same, results that can be expected to be of use in drug design.

PMID- 22586086
TI  - Linking agent-based models and stochastic models of financial markets.
AB  - It is well-known that financial asset returns exhibit fat-tailed distributions
      and long-term memory. These empirical features are the main objectives of
      modeling efforts using (i) stochastic processes to quantitatively reproduce these
      features and (ii) agent-based simulations to understand the underlying
      microscopic interactions. After reviewing selected empirical and theoretical
      evidence documenting the behavior of traders, we construct an agent-based model
      to quantitatively demonstrate that "fat" tails in return distributions arise when
      traders share similar technical trading strategies and decisions. Extending our
      behavioral model to a stochastic model, we derive and explain a set of
      quantitative scaling relations of long-term memory from the empirical behavior of
      individual market participants. Our analysis provides a behavioral interpretation
      of the long-term memory of absolute and squared price returns: They are directly
      linked to the way investors evaluate their investments by applying technical
      strategies at different investment horizons, and this quantitative relationship
      is in agreement with empirical findings. Our approach provides a possible
      behavioral explanation for stochastic models for financial systems in general and
      provides a method to parameterize such models from market data rather than from
      statistical fitting.

PMID- 22586087
TI  - Superresolution imaging of HIV in infected cells with FlAsH-PALM.
AB  - Imaging protein assemblies at molecular resolution without affecting biological
      function is a long-standing goal. The diffraction-limited resolution of
      conventional light microscopy (~200-300 nm) has been overcome by recent
      superresolution (SR) methods including techniques based on accurate localization
      of molecules exhibiting stochastic fluorescence; however, SR methods still suffer
      important restrictions inherent to the protein labeling strategies. Antibody
      labels are encumbered by variable specificity, limited commercial availability
      and affinity, and are mostly restricted to fixed cells. Fluorescent protein
      fusions, though compatible with live cell imaging, substantially increase protein
      size and can interfere with their biological activity. We demonstrate SR imaging
      of proteins tagged with small tetracysteine motifs and the fluorescein arsenical
      helix binder (FlAsH-PALM). We applied FlAsH-PALM to image the integrase enzyme
      (IN) of HIV in fixed and living cells under experimental conditions that fully
      preserved HIV infectivity. The obtained resolution (~30 nm) allowed us to
      characterize the distribution of IN within virions and intracellular complexes
      and to distinguish different HIV structural populations based on their
      morphology. We could thus discriminate ~100 nm long mature conical cores from
      immature Gag shells and observe that in infected cells cytoplasmic (but not
      nuclear) IN complexes display a morphology similar to the conical capsid.
      Together with the presence of capsid proteins, our data suggest that cytoplasmic
      IN is largely present in intact capsids and that these can be found deep within
      the cytoplasm. FlAsH-PALM opens the door to in vivo SR studies of microbial
      complexes within host cells and may help achieve truly molecular resolution.

PMID- 22586088
TI  - Tuning the threshold voltage in electrolyte-gated organic field-effect
      transistors.
AB  - Low-voltage organic field-effect transistors (OFETs) promise for low power
      consumption logic circuits. To enhance the efficiency of the logic circuits, the
      control of the threshold voltage of the transistors are based on is crucial. We
      report the systematic control of the threshold voltage of electrolyte-gated OFETs
      by using various gate metals. The influence of the work function of the metal is
      investigated in metal-electrolyte-organic semiconductor diodes and electrolyte
      gated OFETs. A good correlation is found between the flat-band potential and the
      threshold voltage. The possibility to tune the threshold voltage over half the
      potential range applied and to obtain depletion-like (positive threshold voltage)
      and enhancement (negative threshold voltage) transistors is of great interest
      when integrating these transistors in logic circuits. The combination of a
      depletion-like and enhancement transistor leads to a clear improvement of the
      noise margins in depleted-load unipolar inverters.

PMID- 22586089
TI  - Regulatory changes contribute to the adaptive enhancement of thermogenic capacity
      in high-altitude deer mice.
AB  - In response to hypoxic stress, many animals compensate for a reduced cellular
      O(2) supply by suppressing total metabolism, thereby reducing O(2) demand. For
      small endotherms that are native to high-altitude environments, this is not
      always a viable strategy, as the capacity for sustained aerobic thermogenesis is
      critical for survival during periods of prolonged cold stress. For example,
      survivorship studies of deer mice (Peromyscus maniculatus) have demonstrated that
      thermogenic capacity is under strong directional selection at high altitude.
      Here, we integrate measures of whole-organism thermogenic performance with
      measures of metabolic enzyme activities and genomic transcriptional profiles to
      examine the mechanistic underpinnings of adaptive variation in this complex trait
      in deer mice that are native to different elevations. We demonstrate that
      highland deer mice have an enhanced thermogenic capacity under hypoxia compared
      with lowland conspecifics and a closely related lowland species, Peromyscus
      leucopus. Our findings suggest that the enhanced thermogenic performance of
      highland deer mice is largely attributable to an increased capacity to oxidize
      lipids as a primary metabolic fuel source. This enhanced capacity for aerobic
      thermogenesis is associated with elevated activities of muscle metabolic enzymes
      that influence flux through fatty-acid oxidation and oxidative phosphorylation
      pathways in high-altitude deer mice and by concomitant changes in the expression
      of genes in these same pathways. Contrary to predictions derived from studies of
      humans at high altitude, our results suggest that selection to sustain prolonged
      thermogenesis under hypoxia promotes a shift in metabolic fuel use in favor of
      lipids over carbohydrates.

PMID- 22586090
TI  - Global transcriptome response to ionic liquid by a tropical rain forest soil
      bacterium, Enterobacter lignolyticus.
AB  - To process plant-based renewable biofuels, pretreatment of plant feedstock with
      ionic liquids has significant advantages over current methods for deconstruction
      of lignocellulosic feedstocks. However, ionic liquids are often toxic to the
      microorganisms used subsequently for biomass saccharification and fermentation.
      We previously isolated Enterobacter lignolyticus strain SCF1, a lignocellulolytic
      bacterium from tropical rain forest soil, and report here that it can grow in the
      presence of 0.5 M 1-ethyl-3-methylimidazolium chloride, a commonly used ionic
      liquid. We investigated molecular mechanisms of SCF1 ionic liquid tolerance using
      a combination of phenotypic growth assays, phospholipid fatty acid analysis, and
      RNA sequencing technologies. Potential modes of resistance to 1-ethyl-3
      methylimidazolium chloride include an increase in cyclopropane fatty acids in the
      cell membrane, scavenging of compatible solutes, up-regulation of osmoprotectant
      transporters and drug efflux pumps, and down-regulation of membrane porins. These
      findings represent an important first step in understanding mechanisms of ionic
      liquid resistance in bacteria and provide a basis for engineering microbial
      tolerance.

PMID- 22586091
TI  - Gene regulation via excitation and BDNF is mediated by induction and
      phosphorylation of the Etv1 transcription factor in cerebellar granule cells.
AB  - In maturing postnatal cerebellar granule cells, the Etv1/Er81 transcription
      factor is induced by sequential activity-dependent mechanisms through stimulation
      of AMPA and NMDA receptors, voltage-dependent Nav1.2 Na(+) channels, and voltage
      dependent Ca(2+) channels. Etv1 then up-regulates a battery of maturation genes
      involved in the cerebellar circuitry. In this process, BDNF is also induced and
      participates in the up-regulation of these maturation genes. Using cultures of
      granule cells, we addressed how the activity-dependent and BDNF signaling
      mechanisms converge on the regulation of the representative NR2C NMDA receptor
      and Tiam1 maturation genes. BDNF up-regulated both the NR2C and Tiam1 genes via
      the TrkB-Erk cascade and this up-regulation was blocked not only by inhibition of
      the activity-dependent signaling mechanisms but also by suppression of Etv1
      expression with Etv1 siRNA. Importantly, Etv1 was selectively phosphorylated by
      Erk1/2 in the BDNF signaling cascade, and the inhibition of this phosphorylation
      abrogated the BDNF-induced up-regulation of the NR2C and Tiam1 genes. The
      luciferase reporter assays in combination with mutations of MEK and Etv1
      indicated that the Erk-mediated, phosphorylated Etv1 interacted with the Ets
      motifs of the NR2C promoter sequence and that phosphorylation at both serine 94
      and a cluster of threonines and a serine (Thr139, Thr143, and Ser146) of Etv1 was
      indispensable for the BDNF-mediated activation of the NR2C promoter activity.
      This study demonstrates that the NR2C and Tiam1 maturation genes are
      synergistically controlled by the activity-dependent induction of Etv1 and its
      phosphorylation by the BDNF signaling cascade.

PMID- 22586092
TI  - Nuclear factor of activated T cells (NFATc4) is required for BDNF-dependent
      survival of adult-born neurons and spatial memory formation in the hippocampus.
AB  - New neurons generated in the adult dentate gyrus are constantly integrated into
      the hippocampal circuitry and activated during encoding and recall of new
      memories. Despite identification of extracellular signals that regulate survival
      and integration of adult-born neurons such as neurotrophins and
      neurotransmitters, the nature of the intracellular modulators required to
      transduce those signals remains elusive. Here, we provide evidence of the
      expression and transcriptional activity of nuclear factor of activated T cell c4
      (NFATc4) in hippocampal progenitor cells. We show that NFATc4 calcineurin
      dependent activity is required selectively for survival of adult-born neurons in
      response to BDNF signaling. Indeed, cyclosporin A injection and stereotaxic
      delivery of the BDNF scavenger TrkB-Fc in the mouse dentate gyrus reduce the
      survival of hippocampal adult-born neurons in wild-type but not in NFATc4(-/-)
      mice and do not affect the net rate of neural precursor proliferation and their
      fate commitment. Furthermore, associated with the reduced survival of adult-born
      neurons, the absence of NFATc4 leads to selective defects in LTP and in the
      encoding of hippocampal-dependent spatial memories. Thus, our data demonstrate
      that NFATc4 is essential in the regulation of adult hippocampal neurogenesis and
      identify NFATc4 as a central player of BDNF-driven prosurvival signaling in
      hippocampal adult-born neurons.

PMID- 22586093
TI  - Mass spectral molecular networking of living microbial colonies.
AB  - Integrating the governing chemistry with the genomics and phenotypes of microbial
      colonies has been a "holy grail" in microbiology. This work describes a highly
      sensitive, broadly applicable, and cost-effective approach that allows metabolic
      profiling of live microbial colonies directly from a Petri dish without any
      sample preparation. Nanospray desorption electrospray ionization mass
      spectrometry (MS), combined with alignment of MS data and molecular networking,
      enabled monitoring of metabolite production from live microbial colonies from
      diverse bacterial genera, including Bacillus subtilis, Streptomyces coelicolor,
      Mycobacterium smegmatis, and Pseudomonas aeruginosa. This work demonstrates that,
      by using these tools to visualize small molecular changes within bacterial
      interactions, insights can be gained into bacterial developmental processes as a
      result of the improved organization of MS/MS data. To validate this experimental
      platform, metabolic profiling was performed on Pseudomonas sp. SH-C52, which
      protects sugar beet plants from infections by specific soil-borne fungi [R.
      Mendes et al. (2011) Science 332:1097-1100]. The antifungal effect of strain SH
      C52 was attributed to thanamycin, a predicted lipopeptide encoded by a
      nonribosomal peptide synthetase gene cluster. Our technology, in combination with
      our recently developed peptidogenomics strategy, enabled the detection and
      partial characterization of thanamycin and showed that it is a monochlorinated
      lipopeptide that belongs to the syringomycin family of antifungal agents. In
      conclusion, the platform presented here provides a significant advancement in our
      ability to understand the spatiotemporal dynamics of metabolite production in
      live microbial colonies and communities.

PMID- 22586094
TI  - Macaque studies of vaccine and microbicide combinations for preventing HIV-1
      sexual transmission.
AB  - Vaccination and the application of a vaginal microbicide have traditionally been
      considered independent methods to prevent the sexual transmission of HIV-1 to
      women. Both techniques can be effective in macaque models, and limited efficacy
      has been observed in clinical trials for each. Here, we have addressed whether
      vaccines and microbicides can be used together to provide reinforced protection
      against virus challenge of rhesus macaques. In two separate experiments, four
      groups of animals were vaccinated with a T-cell-based adenovirus (Ad) vectored
      vaccine aimed at reducing postinfection viral loads and/or a partially effective
      dose of a vaginal microbicide aimed at blocking infection of a high-dose vaginal
      challenge with SIVmac251 or SHIV-162P3. In the first study, the only two
      protected animals were in the group that received Ad26/Ad5HVR48 vaccine vectors
      combined with the fusion inhibitor T-1249 as the vaginal microbicide before
      SIVmac251 challenge. In the second study, vaccination with Ad35/Ad26 vectors
      combined with the CCR5 inhibitor maraviroc as the vaginal microbicide led to
      significant reductions of both acquisition of infection and postinfection viral
      loads following SHIV-SF162P3 challenge. As expected, the vaccine by itself
      reduced viral loads but had no acquisition effect, whereas the microbicide had a
      partial acquisition effect but minimal impact on viral loads. For both measures
      of protective efficacy, the vaccine-microbicide combination differed more from
      controls than did either separate intervention. Overall, the data suggest that
      vaccines and microbicides are complementary techniques that may protect better
      when used together than separately.

PMID- 22586096
TI  - China's life satisfaction, 1990-2010.
AB  - Despite its unprecedented growth in output per capita in the last two decades,
      China has essentially followed the life satisfaction trajectory of the central
      and eastern European transition countries--a U-shaped swing and a nil or
      declining trend. There is no evidence of an increase in life satisfaction of the
      magnitude that might have been expected to result from the fourfold improvement
      in the level of per capita consumption that has occurred. As in the European
      countries, in China the trend and U-shaped pattern appear to be related to a
      pronounced rise in unemployment followed by a mild decline, and an accompanying
      dissolution of the social safety net along with growing income inequality. The
      burden of worsening life satisfaction in China has fallen chiefly on the lowest
      socioeconomic groups. An initially highly egalitarian distribution of life
      satisfaction has been replaced by an increasingly unequal one, with decreasing
      life satisfaction in persons in the bottom third of the income distribution and
      increasing life satisfaction in those in the top third.

PMID- 22586095
TI  - Differential effects of lipids and lyso-lipids on the mechanosensitivity of the
      mechanosensitive channels MscL and MscS.
AB  - Mechanosensitive (MS) channels of small (MscS) and large (MscL) conductance are
      the major players in the protection of bacterial cells against hypoosmotic shock.
      Although a great deal is known about structure and function of these channels,
      much less is known about how membrane lipids may influence their
      mechanosensitivity and function. In this study, we use liposome coreconstitution
      to examine the effects of different types of lipids on MscS and MscL
      mechanosensitivity simultaneously using the patch-clamp technique and confocal
      microscopy. Fluorescence lifetime imaging (FLIM)-FRET microscopy demonstrated
      that coreconstitution of MscS and MscL led to clustering of these channels
      causing a significant increase in the MscS activation threshold. Furthermore, the
      MscL/MscS threshold ratio dramatically decreased in thinner compared with thicker
      bilayers and upon addition of cholesterol, known to affect the bilayer thickness,
      stiffness and pressure profile. In contrast, application of micromolar
      concentrations of lysophosphatidylcholine (LPC) led to an increase of the
      MscL/MscS threshold ratio. These data suggest that differences in hydrophobic
      mismatch and bilayer stiffness, change in transbilayer pressure profile, and
      close proximity of MscL and MscS affect the structural dynamics of both channels
      to a different extent. Our findings may have far-reaching implications for other
      types of ion channels and membrane proteins that, like MscL and MscS, may coexist
      in multiple molecular complexes and, consequently, have their activation
      characteristics significantly affected by changes in the lipid environment and
      their proximity to each other.

PMID- 22586097
TI  - Insights into plant size-density relationships from models and agricultural
      crops.
AB  - There is general agreement that competition for resources results in a tradeoff
      between plant mass, M, and density, but the mathematical form of the resulting
      thinning relationship and the mechanisms that generate it are debated. Here, we
      evaluate two complementary models, one based on the space-filling properties of
      canopy geometry and the other on the metabolic basis of resource use. For densely
      packed stands, both models predict that density scales as M(-3/4), energy use as
      M(0), and total biomass as M(1/4). Compilation and analysis of data from 183
      populations of herbaceous crop species, 473 stands of managed tree plantations,
      and 13 populations of bamboo gave four major results: (i) At low initial planting
      densities, crops grew at similar rates, did not come into contact, and attained
      similar mature sizes; (ii) at higher initial densities, crops grew until
      neighboring plants came into contact, growth ceased as a result of competition
      for limited resources, and a tradeoff between density and size resulted in
      critical density scaling as M(-0.78), total resource use as M(-0.02), and total
      biomass as M(0.22); (iii) these scaling exponents are very close to the predicted
      values of M(-3/4), M(0), and M(1/4), respectively, and significantly different
      from the exponents suggested by some earlier studies; and (iv) our data extend
      previously documented scaling relationships for trees in natural forests to small
      herbaceous annual crops. These results provide a quantitative, predictive
      framework with important implications for the basic and applied plant sciences.

PMID- 22586098
TI  - Yno1p/Aim14p, a NADPH-oxidase ortholog, controls extramitochondrial reactive
      oxygen species generation, apoptosis, and actin cable formation in yeast.
AB  - The large protein superfamily of NADPH oxidases (NOX enzymes) is found in members
      of all eukaryotic kingdoms: animals, plants, fungi, and protists. The
      physiological functions of these NOX enzymes range from defense to specialized
      oxidative biosynthesis and to signaling. In filamentous fungi, NOX enzymes are
      involved in signaling cell differentiation, in particular in the formation of
      fruiting bodies. On the basis of bioinformatics analysis, until now it was
      believed that the genomes of unicellular fungi like Saccharomyces cerevisiae and
      Schizosaccharomyces pombe do not harbor genes coding for NOX enzymes.
      Nevertheless, the genome of S. cerevisiae contains nine ORFs showing sequence
      similarity to the catalytic subunits of mammalian NOX enzymes, only some of which
      have been functionally assigned as ferric reductases involved in iron ion
      transport. Here we show that one of the nine ORFs (YGL160W, AIM14) encodes a
      genuine NADPH oxidase, which is located in the endoplasmic reticulum (ER) and
      produces superoxide in a NADPH-dependent fashion. We renamed this ORF YNO1 (yeast
      NADPH oxidase 1). Overexpression of YNO1 causes YCA1-dependent apoptosis, whereas
      deletion of the gene makes cells less sensitive to apoptotic stimuli. Several
      independent lines of evidence point to regulation of the actin cytoskeleton by
      reactive oxygen species (ROS) produced by Yno1p.

PMID- 22586099
TI  - Engineering bone tissue from human embryonic stem cells.
AB  - In extensive bone defects, tissue damage and hypoxia lead to cell death,
      resulting in slow and incomplete healing. Human embryonic stem cells (hESC) can
      give rise to all specialized lineages found in healthy bone and are therefore
      uniquely suited to aid regeneration of damaged bone. We show that the cultivation
      of hESC-derived mesenchymal progenitors on 3D osteoconductive scaffolds in
      bioreactors with medium perfusion leads to the formation of large and compact
      bone constructs. Notably, the implantation of engineered bone in immunodeficient
      mice for 8 wk resulted in the maintenance and maturation of bone matrix, without
      the formation of teratomas that is consistently observed when undifferentiated
      hESCs are implanted, alone or in bone scaffolds. Our study provides a proof of
      principle that tissue-engineering protocols can be successfully applied to hESC
      progenitors to grow bone grafts for use in basic and translational studies.

PMID- 22586100
TI  - Efficient genetic modification and germ-line transmission of primordial germ
      cells using piggyBac and Tol2 transposons.
AB  - The derivation of germ-line competent avian primordial germ cells establishes a
      cell-based model system for the investigation of germ cell differentiation and
      the production of genetically modified animals. Current methods to modify
      primordial germ cells using DNA or retroviral vectors are inefficient and prone
      to epigenetic silencing. Here, we validate the use of transposable elements for
      the genetic manipulation of primordial germ cells. We demonstrate that chicken
      primordial germ cells can be modified in vitro using transposable elements. Both
      piggyBac and Tol2 transposons efficiently transpose primordial germ cells. Tol2
      transposon integration sites were spread throughout both the macro- and
      microchromosomes of the chicken genome and were more prevalent in gene
      transcriptional units and intronic regions, consistent with transposon
      integrations observed in other species. We determined that the presence of
      insulator elements was not required for reporter gene expression from the
      integrated transposon. We further demonstrate that a gene-trap cassette carried
      in the Tol2 transposon can trap and mutate endogenous transcripts in primordial
      germ cells. Finally, we observed that modified primordial germ cells form
      functional gametes as demonstrated by the generation of transgenic offspring that
      correctly expressed a reporter gene carried in the transposon. Transposable
      elements are therefore efficient vectors for the genetic manipulation of
      primordial germ cells and the chicken genome.

PMID- 22586101
TI  - Pupil dilation deconvolution reveals the dynamics of attention at high temporal
      resolution.
AB  - The size of the human pupil increases as a function of mental effort. However,
      this response is slow, and therefore its use is thought to be limited to
      measurements of slow tasks or tasks in which meaningful events are temporally
      well separated. Here we show that high-temporal-resolution tracking of attention
      and cognitive processes can be obtained from the slow pupillary response. Using
      automated dilation deconvolution, we isolated and tracked the dynamics of
      attention in a fast-paced temporal attention task, allowing us to uncover the
      amount of mental activity that is critical for conscious perception of relevant
      stimuli. We thus found evidence for specific temporal expectancy effects in
      attention that have eluded detection using neuroimaging methods such as EEG.
      Combining this approach with other neuroimaging techniques can open many research
      opportunities to study the temporal dynamics of the mind's inner eye in great
      detail.

PMID- 22586103
TI  - Photoperiodic regulation of the seasonal pattern of photosynthetic capacity and
      the implications for carbon cycling.
AB  - Although temperature is an important driver of seasonal changes in photosynthetic
      physiology, photoperiod also regulates leaf activity. Climate change will extend
      growing seasons if temperature cues predominate, but photoperiod-controlled
      species will show limited responsiveness to warming. We show that photoperiod
      explains more seasonal variation in photosynthetic activity across 23 tree
      species than temperature. Although leaves remain green, photosynthetic capacity
      peaks just after summer solstice and declines with decreasing photoperiod, before
      air temperatures peak. In support of these findings, saplings grown at constant
      temperature but exposed to an extended photoperiod maintained high photosynthetic
      capacity, but photosynthetic activity declined in saplings experiencing a
      naturally shortening photoperiod; leaves remained equally green in both
      treatments. Incorporating a photoperiodic correction of photosynthetic physiology
      into a global-scale terrestrial carbon-cycle model significantly improves
      predictions of seasonal atmospheric CO(2) cycling, demonstrating the benefit of
      such a function in coupled climate system models. Accounting for photoperiod
      induced seasonality in photosynthetic parameters reduces modeled global gross
      primary production 2.5% (~4 PgC y(-1)), resulting in a >3% (~2 PgC y(-1))
      decrease of net primary production. Such a correction is also needed in models
      estimating current carbon uptake based on remotely sensed greenness. Photoperiod
      associated declines in photosynthetic capacity could limit autumn carbon gain in
      forests, even if warming delays leaf senescence.

PMID- 22586102
TI  - Repair complexes of FEN1 endonuclease, DNA, and Rad9-Hus1-Rad1 are distinguished
      from their PCNA counterparts by functionally important stability.
AB  - Processivity clamps such as proliferating cell nuclear antigen (PCNA) and the
      checkpoint sliding clamp Rad9/Rad1/Hus1 (9-1-1) act as versatile scaffolds in the
      coordinated recruitment of proteins involved in DNA replication, cell-cycle
      control, and DNA repair. Association and handoff of DNA-editing enzymes, such as
      flap endonuclease 1 (FEN1), with sliding clamps are key processes in biology,
      which are incompletely understood from a mechanistic point of view. We have used
      an integrative computational and experimental approach to define the assemblies
      of FEN1 with double-flap DNA substrates and either proliferating cell nuclear
      antigen or the checkpoint sliding clamp 9-1-1. Fully atomistic models of these
      two ternary complexes were developed and refined through extensive molecular
      dynamics simulations to expose their conformational dynamics. Clustering analysis
      revealed the most dominant conformations accessible to the complexes. The cluster
      centroids were subsequently used in conjunction with single-particle electron
      microscopy data to obtain a 3D EM reconstruction of the human 9-1-1/FEN1/DNA
      assembly at 18-A resolution. Comparing the structures of the complexes revealed
      key differences in the orientation and interactions of FEN1 and double-flap DNA
      with the two clamps that are consistent with their respective functions in
      providing inherent flexibility for lagging strand DNA replication or inherent
      stability for DNA repair.

PMID- 22586104
TI  - Dispersal will limit ability of mammals to track climate change in the Western
      Hemisphere.
AB  - As they have in response to past climatic changes, many species will shift their
      distributions in response to modern climate change. However, due to the
      unprecedented rapidity of projected climatic changes, some species may not be
      able to move their ranges fast enough to track shifts in suitable climates and
      associated habitats. Here, we investigate the ability of 493 mammals to keep pace
      with projected climatic changes in the Western Hemisphere. We modeled the
      velocities at which species will likely need to move to keep pace with projected
      changes in suitable climates. We compared these velocities with the velocities at
      which species are able to move as a function of dispersal distances and dispersal
      frequencies. Across the Western Hemisphere, on average, 9.2% of mammals at a
      given location will likely be unable to keep pace with climate change. In some
      places, up to 39% of mammals may be unable to track shifts in suitable climates.
      Eighty-seven percent of mammalian species are expected to experience reductions
      in range size and 20% of these range reductions will likely be due to limited
      dispersal abilities as opposed to reductions in the area of suitable climate.
      Because climate change will likely outpace the response capacity of many mammals,
      mammalian vulnerability to climate change may be more extensive than previously
      anticipated.

PMID- 22586105
TI  - Junctate is a Ca2+-sensing structural component of Orai1 and stromal interaction
      molecule 1 (STIM1).
AB  - Orai1 and stromal interaction molecule (STIM)1 are critical components of Ca(2+)
      release-activated Ca(2+) (CRAC) channels. Orai1 is a pore subunit of CRAC
      channels, and STIM1 acts as an endoplasmic reticulum (ER) Ca(2+) sensor that
      detects store depletion. Upon store depletion after T-cell receptor stimulation,
      STIM1 translocates and coclusters with Orai1 at sites of close apposition of the
      plasma membrane (PM) and the ER membrane. However, the molecular components of
      these ER-PM junctions remain poorly understood. Using affinity protein
      purification, we uncovered junctate as an interacting partner of Orai1-STIM1
      complex. Furthermore, we identified a Ca(2+)-binding EF-hand motif in the ER
      luminal region of junctate. Mutation of this EF-hand domain of junctate impaired
      its Ca(2+) binding and resulted in partial activation of CRAC channels and
      clustering of STIM1 independently of store depletion. In addition to the known
      mechanisms of STIM1 clustering (i.e., phosphoinositide and Orai1 binding), our
      study identifies an alternate mechanism to recruit STIM1 into the ER-PM junctions
      via binding to junctate. We propose that junctate, a Ca(2+)-sensing ER protein,
      is a structural component of the ER-PM junctions where Orai1 and STIM1 cluster
      and interact in T cells.

PMID- 22586106
TI  - PKCalpha is genetically linked to memory capacity in healthy subjects and to risk
      for posttraumatic stress disorder in genocide survivors.
AB  - Strong memory of a traumatic event is thought to contribute to the development
      and symptoms of posttraumatic stress disorder (PTSD). Therefore, a genetic
      predisposition to build strong memories could lead to increased risk for PTSD
      after a traumatic event. Here we show that genetic variability of the gene
      encoding PKCalpha (PRKCA) was associated with memory capacity--including aversive
      memory--in nontraumatized subjects of European descent. This finding was
      replicated in an independent sample of nontraumatized subjects, who additionally
      underwent functional magnetic resonance imaging (fMRI). fMRI analysis revealed
      PRKCA genotype-dependent brain activation differences during successful encoding
      of aversive information. Further, the identified genetic variant was also related
      to traumatic memory and to the risk for PTSD in heavily traumatized survivors of
      the Rwandan genocide. Our results indicate a role for PKCalpha in memory and
      suggest a genetic link between memory and the risk for PTSD.

PMID- 22586107
TI  - G-protein-mediated inhibition of the Trp channel TRPM1 requires the Gbetagamma
      dimer.
AB  - ON bipolar cells are critical for the function of the ON pathway in the visual
      system. They express a metabotropic glutamate receptor (mGluR6) that, when
      activated, couples to the G(o) class of G protein. The channel that is primarily
      responsible for the synaptic response has been recently identified as the
      transient receptor potential cation channel subfamily M member 1 (TRPM1); TRPM1
      is negatively coupled to the mGluR6/Go cascade such that activation of the
      cascade results in closure of the channel. Light indirectly opens TRPM1 by
      reducing transmitter release from presynaptic photoreceptors, resulting in a
      decrease in mGluR6 activation. Conversely, in the dark, binding of synaptic
      glutamate to mGluR6 inhibits TRPM1 current. Closure of TRPM1 by G-protein
      activation in the dark is a critical step in the process of ON bipolar cell
      signal transduction, but the precise pathway linking these two events is not
      understood. To address this question, we measured TRPM1 activity in retinal
      bipolar cells, in human ependymal melanocytes (HEMs) that endogenously express
      TRPM1, and in HEK293 cells transfected with TRPM1. Dialysis of the Gbetagamma
      subunit dimer, but not Galpha(o), closed TRPM1 channels in every cell type that
      we tested. In addition, activation of an endogenous G-protein-coupled receptor
      pathway in HEK293 cells that releases Gbetagamma without activating Go protein
      also closed TRPM1 channels. These results suggest a model in which the Gbetagamma
      dimer that is released as a result of the dissociation from Galpha(o) upon
      activation of mGluR6 closes the TRPM1 channel, perhaps via a direct interaction.

PMID- 22586108
TI  - Isolation of phosphatidylethanolamine as a solitary cofactor for prion formation
      in the absence of nucleic acids.
AB  - Infectious prions containing the pathogenic conformer of the mammalian prion
      protein (PrP(Sc)) can be produced de novo from a mixture of the normal conformer
      (PrP(C)) with RNA and lipid molecules. Recent reconstitution studies indicate
      that nucleic acids are not required for the propagation of mouse prions in vitro,
      suggesting the existence of an alternative prion propagation cofactor in brain
      tissue. However, the identity and functional properties of this unique cofactor
      are unknown. Here, we show by purification and reconstitution that the molecule
      responsible for the nuclease-resistant cofactor activity in brain is endogenous
      phosphatidylethanolamine (PE). Synthetic PE alone facilitates conversion of
      purified recombinant (rec)PrP substrate into infectious recPrP(Sc) molecules.
      Other phospholipids, including phosphatidylcholine, phosphatidylserine,
      phosphatidylinositol, and phosphatidylglycerol, were unable to facilitate
      recPrP(Sc) formation in the absence of RNA. PE facilitated the propagation of
      PrP(Sc) molecules derived from all four different animal species tested including
      mouse, suggesting that unlike RNA, PE is a promiscuous cofactor for PrP(Sc)
      formation in vitro. Phospholipase treatment abolished the ability of brain
      homogenate to reconstitute the propagation of both mouse and hamster PrP(Sc)
      molecules. Our results identify a single endogenous cofactor able to facilitate
      the formation of prions from multiple species in the absence of nucleic acids or
      other polyanions.

PMID- 22586109
TI  - Molecular tracing of the emergence, adaptation, and transmission of hospital
      associated methicillin-resistant Staphylococcus aureus.
AB  - Hospital-associated infections caused by methicillin-resistant Staphylococcus
      aureus (MRSA) are a global health burden dominated by a small number of bacterial
      clones. The pandemic EMRSA-16 clone (ST36-II) has been widespread in UK hospitals
      for 20 y, but its evolutionary origin and the molecular basis for its hospital
      association are unclear. We carried out a Bayesian phylogenetic reconstruction on
      the basis of the genome sequences of 87 S. aureus isolates including 60 EMRSA-16
      and 27 additional clonal complex 30 (CC30) isolates, collected from patients in
      three continents over a 53-y period. The three major pandemic clones to originate
      from the CC30 lineage, including phage type 80/81, Southwest Pacific, and EMRSA
      16, shared a most recent common ancestor that existed over 100 y ago, whereas the
      hospital-associated EMRSA-16 clone is estimated to have emerged about 35 y ago.
      Our CC30 genome-wide analysis revealed striking molecular correlates of hospital-
      or community-associated pandemics represented by mobile genetic elements and
      nonsynonymous mutations affecting antibiotic resistance and virulence.
      Importantly, phylogeographic analysis indicates that EMRSA-16 spread within the
      United Kingdom by transmission from hospitals in large population centers in
      London and Glasgow to regional health-care settings, implicating patient
      referrals as an important cause of nationwide transmission. Taken together, the
      high-resolution phylogenomic approach used resulted in a unique understanding of
      the emergence and transmission of a major MRSA clone and provided molecular
      correlates of its hospital adaptation. Similar approaches for hospital-associated
      clones of other bacterial pathogens may inform appropriate measures for
      controlling their intra- and interhospital spread.

PMID- 22586110
TI  - Hijacking a hydroxyethyl unit from a central metabolic ketose into a nonribosomal
      peptide assembly line.
AB  - Nonribosomal peptide synthetases (NRPSs) usually catalyze the biosynthesis of
      peptide natural products by sequential selection, activation, and condensation of
      amino acid precursors. It was reported that some fatty acids, alpha-ketoacids,
      and alpha-hydroxyacids originating from amino acid metabolism as well as
      polyketide-derived units can also be used by NRPS assembly lines as an
      alternative to amino acids. Ecteinascidin 743 (ET-743), naphthyridinomycin (NDM),
      and quinocarcin (QNC) are three important antitumor natural products belonging to
      the tetrahydroisoquinoline family. Although ET-743 has been approved as an
      anticancer drug, the origin of an identical two-carbon (C(2)) fragment among
      these three antibiotics has not been elucidated despite much effort in the
      biosynthetic research in the past 30 y. Here we report that two unexpected two
      component transketolases (TKases), NapB/NapD in the NDM biosynthetic pathway and
      QncN/QncL in QNC biosynthesis, catalyze the transfer of a glycolaldehyde unit
      from ketose to the lipoyl group to yield the glycolicacyl lipoic acid
      intermediate and then transfer the C(2) unit to an acyl carrier protein (ACP) to
      form glycolicacyl-S-ACP as an extender unit for NRPS. Our results demonstrate a
      unique NRPS extender unit directly derived from ketose phosphates through
      (alpha,beta-dihydroxyethyl)-thiamin diphosphate and a lipoyl group-tethered ester
      intermediate catalyzed by the TKase-ACP platform in the context of NDM and QNC
      biosynthesis, all of which also highlights the biosynthesis of ET-743. This
      hybrid system and precursor are distinct from the previously described universal
      modes involving the NRPS machinery. They exemplify an alternate strategy in
      hybrid NRPS biochemistry and enrich the diversity of precursors for NRPS
      combinatorial biosynthesis.

PMID- 22586111
TI  - Context and dating of Aurignacian vulvar representations from Abri Castanet,
      France.
AB  - We report here on the 2007 discovery, in perfect archaeological context, of part
      of the engraved and ocre-stained undersurface of the collapsed rockshelter
      ceiling from Abri Castanet, Dordogne, France. The decorated surface of the 1.5-t
      roof-collapse block was in direct contact with the exposed archaeological surface
      onto which it fell. Because there was no sedimentation between the engraved
      surface and the archaeological layer upon which it collapsed, it is clear that
      the Early Aurignacian occupants of the shelter were the authors of the ceiling
      imagery. This discovery contributes an important dimension to our understanding
      of the earliest graphic representation in southwestern France, almost all of
      which was discovered before modern methods of archaeological excavation and
      analysis. Comparison of the dates for the Castanet ceiling and those directly
      obtained from the Chauvet paintings reveal that the "vulvar" representations from
      southwestern France are as old or older than the very different wall images from
      Chauvet.

PMID- 22586112
TI  - Causal effect of education on mortality in a quasi-experiment on 1.2 million
      Swedes.
AB  - In 1949-1962, Sweden implemented a 1-y increase in compulsory schooling as a
      quasi-experiment. Each year, children in a number of municipalities were exposed
      to the reform and others were kept as controls, allowing us to test the
      hypothesis that education is causally related to mortality. We studied all
      children born between 1943 and 1955, in 900 Swedish municipalities, with control
      for birth-cohort and area differences. Primary outcome measures are all-cause and
      cause-specific mortality until the end of 2007. The analyses include 1,247,867
      individuals, of whom 92,351 died. We found lower all-cause mortality risk in the
      experimental group after age 40 [hazard ratio (HR) = 0.96, 95% confidence
      interval (CI) 0.93-0.99] but not before (HR = 1.03, 95% CI 0.98-1.07) or during
      the whole follow-up (HR = 0.98, 95% CI 0.95-1.01). After age 40, the experimental
      group had lower mortality from overall cancer, lung cancer, and accidents. In
      addition, exposed women had lower mortality from ischemic heart disease, and
      exposed men lower mortality from overall external causes. In analyses stratified
      for final educational level, we found lower mortality in the experimental group
      within the strata that settled for compulsory schooling only (HR = 0.94, 95% CI
      0.89-0.99) and compulsory schooling plus vocational training (HR = 0.92, 95% CI
      0.88-0.97). Thus, the experimental group had lower mortality from causes known to
      be related to education. Lower mortality in the experimental group was also found
      among the least educated, a group that clearly benefited from the reform in terms
      of educational length. However, all estimates are small and there was no evident
      impact of the reform on all-cause mortality in all ages.

PMID- 22586113
TI  - Controlling the shapes and assemblages of graphene.

PMID- 22586114
TI  - Omega-3 fatty acids cause dramatic changes in TLR4 and purinergic eicosanoid
      signaling.
AB  - Dietary fish oil containing omega3 fatty acids, eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA), elicit cardioprotective and anti-inflammatory effects
      through unresolved mechanisms that may involve competition and inhibition at
      multiple levels. Here, we report the effects of arachidonic acid (AA), EPA, and
      DHA supplementation on membrane incorporation, phospholipase A(2) catalyzed
      release, and eicosanoid production in RAW264.7 macrophages. Using a targeted
      lipidomics approach, we observed that Toll-like receptor 4 and purinergic
      receptor activation of supplemented cells leads to the release of 22-carbon fatty
      acids that potently inhibit cyclooxygenase pathways. This inhibition was able to
      shunt metabolism of AA to lipoxygenase pathways, augmenting leukotriene and other
      lipoxygenase mediator synthesis. In resident peritoneal macrophages,
      docosapentaenoic acid (DPA) was responsible for cyclooxygenase inhibition after
      EPA supplementation, offering fresh insights into how EPA exerts anti
      inflammatory effects indirectly through elongation to 22-carbon DPA.

PMID- 22586115
TI  - Peptidomics approach to elucidate the proteolytic regulation of bioactive
      peptides.
AB  - Peptide hormones and neuropeptides have important roles in physiology and
      therefore the regulation of these bioactive peptides is of great interest. In
      some cases proteolysis controls the concentrations and signaling of bioactive
      peptides, and the peptidases that mediate this biochemistry have proven to be
      extremely successful drug targets. Due to the lack of any general method to
      identify these peptidases, however, the role of proteolysis in the regulation of
      most neuropeptides and peptide hormones is unknown. This limitation prompted us
      to develop an advanced peptidomics-based strategy to identify the peptidases
      responsible for the proteolysis of significant bioactive peptides. The
      application of this approach to calcitonin gene-related peptide (CGRP), a
      neuropeptide associated with blood pressure and migraine, revealed the endogenous
      CGRP cleavage sites. This information was then used to biochemically purify the
      peptidase capable of proteolysis of CGRP at those cleavage sites, which led to
      the identification of insulin-degrading enzyme (IDE) as a candidate CGRP
      degrading enzyme. CGRP had not been identified as an IDE substrate before and we
      tested the physiological relevance of this interaction by quantitative
      measurements of CGRP using IDE null (IDE(-/-)) mice. In the absence of IDE, full
      length CGRP levels are elevated in vivo, confirming IDE as an endogenous CGRP
      degrading enzyme. By linking CGRP and IDE, this strategy uncovers a previously
      unknown pathway for CGRP regulation and characterizes an additional role for IDE.
      More generally, this work suggests that this may be an effective general strategy
      for characterizing these pathways and peptidases moving forward.

PMID- 22586116
TI  - Role for gene looping in intron-mediated enhancement of transcription.
AB  - Intron-containing genes are often transcribed more efficiently than nonintronic
      genes. The effect of introns on transcription of genes is an evolutionarily
      conserved feature, being exhibited by such diverse organisms as yeast, plants,
      flies, and mammals. The mechanism of intron-mediated transcriptional activation,
      however, is not entirely clear. To address this issue, we inserted an intron in
      INO1, which is a nonintronic gene, and deleted the intron from ASC1, which
      contains a natural intron. We then compared transcription of INO1 and ASC1 genes
      in the presence and absence of an intron. Transcription of both genes was
      significantly stimulated by the intron. The introns have a direct role in
      enhancing transcription of INO1 and ASC1 because there was a marked increase in
      nascent transcripts from these genes in the presence of an intron. Intron
      mediated enhancement of transcription required a splicing competent intron.
      Interestingly, both INO1 and ASC1 were in a looped configuration when their genes
      contained an intron. Intron-dependent gene looping involved a physical
      interaction of the promoter and the terminator regions. In addition, the promoter
      region interacted with the 5' splice site and the terminator with the 3' splice
      site. Intron-mediated enhancement of transcription was completely abolished in
      the looping defective sua7-1 strain. No effect on splicing, however, was observed
      in sua7-1 strain. On the basis of these results, we propose a role for gene
      looping in intron-mediated transcriptional activation of genes in yeast.

PMID- 22586117
TI  - Sulfur isotope variability of oceanic DMSP generation and its contributions to
      marine biogenic sulfur emissions.
AB  - Oceanic dimethylsulfoniopropionate (DMSP) is the precursor to dimethylsulfide
      (DMS), which plays a role in climate regulation through transformation to
      methanesulfonic acid (MSA) and non-seasalt sulfate (NSS-SO(4)(2-)) aerosols.
      Here, we report measurements of the abundance and sulfur isotope compositions of
      DMSP from one phytoplankton species (Prorocentrum minimum) and five intertidal
      macroalgal species (Ulva lactuca, Ulva linza, Ulvaria obscura, Ulva prolifera,
      and Polysiphonia hendryi) in marine waters. We show that the sulfur isotope
      compositions (delta(34)S) of DMSP are depleted in (34)S relative to the source
      seawater sulfate by ~1-30/00 and are correlated with the observed intracellular
      content of methionine, suggesting a link to metabolic pathways of methionine
      production. We suggest that this variability of delta(34)S is transferred to
      atmospheric geochemical products of DMSP degradation (DMS, MSA, and NSS-SO(4)(2
      )), carrying implications for the interpretation of variability in delta(34)S of
      MSA and NSS-SO(4)(2-) that links them to changes in growth conditions and
      populations of DMSP producers rather than to the contributions of DMS and non-DMS
      sources.

PMID- 22586118
TI  - Reactive oxygen species are second messengers of neurokinin signaling in
      peripheral sensory neurons.
AB  - Substance P (SP) is a prominent neuromodulator, which is produced and released by
      peripheral damage-sensing (nociceptive) neurons; these neurons also express SP
      receptors. However, the mechanisms of peripheral SP signaling are poorly
      understood. We report a signaling pathway of SP in nociceptive neurons: Acting
      predominantly through NK1 receptors and G(i/o) proteins, SP stimulates increased
      release of reactive oxygen species from the mitochondrial electron transport
      chain. Reactive oxygen species, functioning as second messengers, induce
      oxidative modification and augment M-type potassium channels, thereby suppressing
      excitability. This signaling cascade requires activation of phospholipase C but
      is largely uncoupled from the inositol 1,4,5-trisphosphate sensitive Ca(2+)
      stores. In rats SP causes sensitization of TRPV1 and produces thermal
      hyperalgesia. However, the lack of coupling between SP signaling and inositol
      1,4,5-trisphosphate sensitive Ca(2+) stores, together with the augmenting effect
      on M channels, renders the SP pathway ineffective to excite nociceptors acutely
      and produce spontaneous pain. Our study describes a mechanism for neurokinin
      signaling in sensory neurons and provides evidence that spontaneous pain and
      hyperalgesia can have distinct underlying mechanisms within a single nociceptive
      neuron.

PMID- 22586119
TI  - LPS remodeling is an evolved survival strategy for bacteria.
AB  - Maintenance of membrane function is essential and regulated at the genomic,
      transcriptional, and translational levels. Bacterial pathogens have a variety of
      mechanisms to adapt their membrane in response to transmission between
      environment, vector, and human host. Using a well-characterized model of lipid A
      diversification (Francisella), we demonstrate temperature-regulated membrane
      remodeling directed by multiple alleles of the lipid A-modifying N
      acyltransferase enzyme, LpxD. Structural analysis of the lipid A at environmental
      and host temperatures revealed that the LpxD1 enzyme added a 3-OH C18 acyl group
      at 37  degrees C (host), whereas the LpxD2 enzyme added a 3-OH C16 acyl group at
      18  degrees C (environment). Mutational analysis of either of the individual
      Francisella lpxD genes altered outer membrane (OM) permeability, antimicrobial
      peptide, and antibiotic susceptibility, whereas only the lpxD1-null mutant was
      attenuated in mice and subsequently exhibited protection against a lethal WT
      challenge. Additionally, growth-temperature analysis revealed transcriptional
      control of the lpxD genes and posttranslational control of the LpxD1 and LpxD2
      enzymatic activities. These results suggest a direct mechanism for LPS/lipid A
      level modifications resulting in alterations of membrane fluidity, as well as
      integrity and may represent a general paradigm for bacterial membrane adaptation
      and virulence-state adaptation.

PMID- 22586121
TI  - Functional intestinal stem cells after Paneth cell ablation induced by the loss
      of transcription factor Math1 (Atoh1).
AB  - Intestinal epithelium has the capacity to self-renew and generate differentiated
      cells through the existence of two types of epithelial stem cells: active crypt
      base columnar cells (CBCs) and quiescent +4 cells. The behaviors of these cells
      are regulated both by intrinsic programs and by extrinsic signals sent by
      neighboring cells, which define the niche. It is clear that the beta-catenin
      pathway acts as an essential intrinsic signal for the maintenance and
      proliferation of CBC, and it was recently proposed that Paneth cells provide a
      crucial niche by secreting Wingless/Int (Wnt) ligands. Here, we examined the
      effect of disrupting the intestinal stem cell niche by inducible deletion of the
      transcription factor Math1 (Atoh1), an essential driver of secretory cell
      differentiation. We found that complete loss of Paneth cells attributable to
      Math1 deficiency did not perturb the crypt architecture and allowed the
      maintenance and proliferation of CBCs. Indeed, Math1-deficient crypt cells
      tolerated in vivo Paneth cell loss and maintained active beta-catenin signaling
      but could not grow ex vivo without exogenous Wnt, implying that, in vivo,
      underlying mucosal cells act as potential niche. Upon irradiation, Math1
      deficient crypt cells regenerated and CBCs continued cycling. Finally, CBC stem
      cells deficient in adenomatous polyposis coli (Apc) and Math1 were able to
      promote intestinal tumorigenesis. We conclude that in vivo, Math1-deficient
      crypts counteract the absence of Paneth cell-derived Wnts and prevent CBC stem
      cell exhaustion.

PMID- 22586120
TI  - Cooperative interactions of BRAFV600E kinase and CDKN2A locus deficiency in
      pediatric malignant astrocytoma as a basis for rational therapy.
AB  - Although malignant astrocytomas are a leading cause of cancer-related death in
      children, rational therapeutic strategies are lacking. We previously identified
      activating mutations of v-raf murine sarcoma viral oncogene homolog B1 (BRAF)
      (BRAF(T1799A) encoding BRAF(V600E)) in association with homozygous cyclin
      dependent kinase inhibitor 2A (CDKN2A, encoding p14ARF and p16Ink4a) deletions in
      pediatric infiltrative astrocytomas. Here we report that BRAF(V600E) expression
      in neural progenitors (NPs) is insufficient for tumorigenesis and increases NP
      cellular differentiation as well as apoptosis. In contrast, astrocytomas are
      readily generated from NPs with additional Ink4a-Arf deletion. The BRAF(V600E)
      inhibitor PLX4720 significantly increased survival of mice after intracranial
      transplant of genetically relevant murine or human astrocytoma cells. Moreover,
      combination therapy using PLX4720 plus the Cyclin-dependent kinase (CDK) 4/6
      specific inhibitor PD0332991 further extended survival relative to either
      monotherapy. Our findings indicate a rational therapeutic strategy for treating a
      subset of pediatric astrocytomas with BRAF(V600E) mutation and CDKN2A deficiency.

PMID- 22586122
TI  - Identification of a tetratricopeptide repeat-like domain in the nicastrin subunit
      of gamma-secretase using synthetic antibodies.
AB  - The gamma-secretase complex, composed of presenilin, anterior-pharynx-defective
      1, nicastrin, and presenilin enhancer 2, catalyzes the intramembranous processing
      of a wide variety of type I membrane proteins, including amyloid precursor
      protein (APP) and Notch. Earlier studies have revealed that nicastrin, a type I
      membrane-anchored glycoprotein, plays a role in gamma-secretase assembly and
      trafficking and has been proposed to bind substrates. To gain more insights
      regarding nicastrin structure and function, we generated a conformation-specific
      synthetic antibody and used it as a molecular probe to map functional domains
      within nicastrin ectodomain. The antibody bound to a conformational epitope
      within a nicastrin segment encompassing residues 245-630 and inhibited the
      processing of APP and Notch substrates in in vitro gamma-secretase activity
      assays, suggesting that a functional domain pertinent to gamma-secretase activity
      resides within this region. Epitope mapping and database searches revealed the
      presence of a structured segment, located downstream of the previously identified
      DAP domain (DYIGS and peptidase; residues 261-502), that is homologous to a
      tetratricopeptide repeat (TPR) domain commonly involved in peptide recognition.
      Mutagenesis analyses within the predicted TPR-like domain showed that disruption
      of the signature helical structure resulted in the loss of gamma-secretase
      activity but not the assembly of the gamma-secretase and that Leu571 within the
      TPR-like domain plays an important role in mediating substrate binding. Taken
      together, these studies offer provocative insights pertaining to the structural
      basis for nicastrin function as a "substrate receptor" within the gamma-secretase
      complex.

PMID- 22586123
TI  - Higher-order motion sensitivity in fly visual circuits.
AB  - In higher-order motion stimuli, the direction of object motion does not follow
      the direction of luminance change. Such stimuli could be generated by the wing
      movements of a flying butterfly and further complicated by its motion in and out
      of shadows. Human subjects readily perceive the direction of higher-order motion,
      although this stands in stark contrast to prevailing motion vision models. Flies
      and humans compute motion in similar ways, and because flies behaviorally track
      bars containing higher-order motion cues, they become an attractive model system
      for investigating the neurophysiology underlying higher-order motion sensitivity.
      We here use intracellular electrophysiology of motion-vision-sensitive neurons in
      the hoverfly lobula plate to quantify responses to stimuli containing higher
      order motion. We show that motion sensitivity can be broken down into two
      separate streams, directionally coding for elementary motion and figure motion,
      respectively, and that responses to Fourier and theta motion can be predicted
      from these. The sensitivity is affected both by the stimulus' time course and by
      the neuron's underlying receptive field. Responses to preferred-direction theta
      motion are sexually dimorphic and particularly robust along the visual midline.

PMID- 22586124
TI  - Liver-stage malaria parasites vulnerable to diverse chemical scaffolds.
AB  - Human malaria infection begins with a one-time asymptomatic liver stage followed
      by a cyclic symptomatic blood stage. All high-throughput malaria drug discovery
      efforts have focused on the cyclic blood stage, which has limited potential for
      the prophylaxis, transmission blocking, and eradication efforts that will be
      needed in the future. To address these unmet needs, a high-throughput phenotypic
      liver-stage Plasmodium parasite screen was developed to systematically identify
      molecules with liver-stage efficacy. The screen recapitulates liver-stage
      infection by isolating luciferase-expressing Plasmodium berghei parasites
      directly from the salivary glands of infected mosquitoes, adding them to
      confluent human liver cells in 384-well plates, and measuring luciferase activity
      after a suitable incubation period. Screening 5,375 known bioactive compounds
      identified 37 liver-stage malaria inhibitors with diverse modes of action, as
      shown by inhibition time course experiments. Further analysis of the hits in the
      Food and Drug Administration-approved drug subset revealed compounds that seem to
      act specifically on the liver stage of infection, suggesting that this phase of
      the parasite's life cycle presents a promising area for new drug discovery.
      Notably, many active compounds in this screen have molecular structures and
      putative targets distinctly different from those of known antimalarial agents.

PMID- 22586125
TI  - Deep brain stimulation of the ventral striatum enhances extinction of conditioned
      fear.
AB  - Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS)
      reduces symptoms of intractable obsessive-compulsive disorder (OCD), but the
      mechanism of action is unknown. OCD is characterized by avoidance behaviors that
      fail to extinguish, and DBS could act, in part, by facilitating extinction of
      fear. We investigated this possibility by using auditory fear conditioning in
      rats, for which the circuits of fear extinction are well characterized. We found
      that DBS of the VS (the VC/VS homolog in rats) during extinction training reduced
      fear expression and strengthened extinction memory. Facilitation of extinction
      was observed for a specific zone of dorsomedial VS, just above the anterior
      commissure; stimulation of more ventrolateral sites in VS impaired extinction.
      DBS effects could not be obtained with pharmacological inactivation of either
      dorsomedial VS or ventrolateral VS, suggesting an extrastriatal mechanism.
      Accordingly, DBS of dorsomedial VS (but not ventrolateral VS) increased
      expression of a plasticity marker in the prelimbic and infralimbic prefrontal
      cortices, the orbitofrontal cortex, the amygdala central nucleus (lateral
      division), and intercalated cells, areas known to learn and express extinction.
      Facilitation of fear extinction suggests that, in accord with clinical
      observations, DBS could augment the effectiveness of cognitive behavioral
      therapies for OCD.

PMID- 22586126
TI  - Apex predators and trophic cascades in large marine ecosystems: learning from
      serendipity.

PMID- 22586128
TI  - The polymorphism rs944289 predisposes to papillary thyroid carcinoma through a
      large intergenic noncoding RNA gene of tumor suppressor type.
AB  - A genome-wide association study of papillary thyroid carcinoma (PTC) pinpointed
      two independent SNPs (rs944289 and rs965513) located in regions containing no
      annotated genes (14q13.3 and 9q22.33, respectively). Here, we describe a unique,
      long, intergenic, noncoding RNA gene (lincRNA) named Papillary Thyroid Carcinoma
      Susceptibility Candidate 3 (PTCSC3) located 3.2 kb downstream of rs944289 at
      14q.13.3 and the expression of which is strictly thyroid specific. By
      quantitative PCR, PTCSC3 expression was strongly down-regulated (P = 2.84 * 10(
      14)) in thyroid tumor tissue of 46 PTC patients and the risk allele (T) was
      associated with the strongest suppression (genotype [TT] (n = 21) vs. [CT] (n =
      19), P = 0.004). In adjacent unaffected thyroid tissue, the genotype [TT] was
      associated with up-regulation of PTCSC3 ([TT] (n = 21) vs. [CT] (n = 19), P =
      0.034). The SNP rs944289 was located in a binding site for the CCAAT/enhancer
      binding proteins (C/EBP) alpha and beta. The risk allele destroyed the binding
      site in silico. Both C/EBPalpha and C/EBPbeta activated the PTCSC3 promoter in
      reporter assays (P = 0.0009 and P = 0.0014, respectively) and the risk allele
      reduced the activation compared with the nonrisk allele (C) (P = 0.026 and P =
      0.048, respectively). Restoration of PTCSC3 expression in PTC cell line cells
      (TPC-1 and BCPAP) inhibited cell growth (P = 0.002 and P = 0.019, respectively)
      and affected the expression of genes involved in DNA replication, recombination
      and repair, cellular movement, tumor morphology, and cell death. Our data suggest
      that SNP rs944289 predisposes to PTC through a previously uncharacterized, long
      intergenic noncoding RNA gene (PTCSC3) that has the characteristics of a tumor
      suppressor.

PMID- 22586127
TI  - Y-chromosome analysis reveals genetic divergence and new founding native lineages
      in Athapaskan- and Eskimoan-speaking populations.
AB  - For decades, the peopling of the Americas has been explored through the analysis
      of uniparentally inherited genetic systems in Native American populations and the
      comparison of these genetic data with current linguistic groupings. In northern
      North America, two language families predominate: Eskimo-Aleut and Na-Dene.
      Although the genetic evidence from nuclear and mtDNA loci suggest that speakers
      of these language families share a distinct biological origin, this model has not
      been examined using data from paternally inherited Y chromosomes. To test this
      hypothesis and elucidate the migration histories of Eskimoan- and Athapaskan
      speaking populations, we analyzed Y-chromosomal data from Inuvialuit, Gwich'in,
      and Tlich populations living in the Northwest Territories of Canada. Over 100
      biallelic markers and 19 chromosome short tandem repeats (STRs) were genotyped to
      produce a high-resolution dataset of Y chromosomes from these groups. Among these
      markers is an SNP discovered in the Inuvialuit that differentiates them from
      other Aboriginal and Native American populations. The data suggest that Canadian
      Eskimoan- and Athapaskan-speaking populations are genetically distinct from one
      another and that the formation of these groups was the result of two population
      expansions that occurred after the initial movement of people into the Americas.
      In addition, the population history of Athapaskan speakers is complex, with the
      Tlich being distinct from other Athapaskan groups. The high-resolution biallelic
      data also make clear that Y-chromosomal diversity among the first Native
      Americans was greater than previously recognized.

PMID- 22586129
TI  - Quorum-sensing agr mediates bacterial oxidation response via an intramolecular
      disulfide redox switch in the response regulator AgrA.
AB  - Oxidation sensing and quorum sensing significantly affect bacterial physiology
      and host-pathogen interactions. However, little attention has been paid to the
      cross-talk between these two seemingly orthogonal signaling pathways. Here we
      show that the quorum-sensing agr system has a built-in oxidation-sensing
      mechanism through an intramolecular disulfide switch possessed by the DNA-binding
      domain of the response regulator AgrA. Biochemical and mass spectrometric
      analysis revealed that oxidation induces the intracellular disulfide bond
      formation between Cys-199 and Cys-228, thus leading to dissociation of AgrA from
      DNA. Molecular dynamics (MD) simulations suggest that the disulfide bond
      formation generates a steric clash responsible for the abolished DNA binding of
      the oxidized AgrA. Mutagenesis studies further established that Cys-199 is
      crucial for oxidation sensing. The oxidation-sensing role of Cys-199 is further
      supported by the observation that the mutant Staphylococcus aureus strain
      expressing AgrAC199S is more susceptible to H(2)O(2) owing to repression of the
      antioxidant bsaA gene under oxidative stress. Together, our results show that
      oxidation sensing is a component of the quorum-sensing agr signaling system,
      which serves as an intrinsic checkpoint to ameliorate the oxidation burden caused
      by intense metabolic activity and potential host immune response.

PMID- 22586130
TI  - Comparative genomics of rhizobia nodulating soybean suggests extensive
      recruitment of lineage-specific genes in adaptations.
AB  - The rhizobium-legume symbiosis has been widely studied as the model of
      mutualistic evolution and the essential component of sustainable agriculture.
      Extensive genetic and recent genomic studies have led to the hypothesis that many
      distinct strategies, regardless of rhizobial phylogeny, contributed to the varied
      rhizobium-legume symbiosis. We sequenced 26 genomes of Sinorhizobium and
      Bradyrhizobium nodulating soybean to test this hypothesis. The Bradyrhizobium
      core genome is disproportionally enriched in lipid and secondary metabolism,
      whereas several gene clusters known to be involved in osmoprotection and
      adaptation to alkaline pH are specific to the Sinorhizobium core genome. These
      features are consistent with biogeographic patterns of these bacteria.
      Surprisingly, no genes are specifically shared by these soybean microsymbionts
      compared with other legume microsymbionts. On the other hand, phyletic patterns
      of 561 known symbiosis genes of rhizobia reflected the species phylogeny of these
      soybean microsymbionts and other rhizobia. Similar analyses with 887 known
      functional genes or the whole pan genome of rhizobia revealed that only the
      phyletic distribution of functional genes was consistent with the species tree of
      rhizobia. Further evolutionary genetics revealed that recombination dominated the
      evolution of core genome. Taken together, our results suggested that faithfully
      vertical genes were rare compared with those with history of recombination
      including lateral gene transfer, although rhizobial adaptations to symbiotic
      interactions and other environmental conditions extensively recruited lineage
      specific shell genes under direct or indirect control through the speciation
      process.

PMID- 22586131
TI  - Commentary: a new dimension--studies in schoolchildren.

PMID- 22586132
TI  - Paternal alcohol consumption, family transition and child development in a former
      Soviet country.
AB  - BACKGROUND: Although major societal changes have been observed in former Soviet
      countries, the child health consequences of these changes have rarely been
      studied. METHODS: We examined the associations of paternal alcohol consumption
      and family transitions with cognitive ability and behaviour problems among
      healthy, early school-age Belarusian children. Our study is based on follow-up of
      children aged 6.5 years participating in a cluster-randomized trial of a
      breastfeeding promotion intervention. Paternal alcohol consumption was measured
      at follow-up and classified into three categories: at least weekly consumption of
      heavy (>= 6 standard units per occasion), moderate (4-5 units per occasion), or
      light (<= 3 units per occasion) or infrequent drinking. Family transition from
      birth to age 6.5 years was categorized into living stably with an intact family,
      having transitioned into a stepfamily, having transitioned into a single-parent
      family and living stably with a single-parent family. Mean differences in
      intelligence quotient (IQ) measured with the Wechsler Abbreviated Scales of
      Intelligence and in behaviour problems measured with the Strengths and
      Difficulties Questionnaire were compared according to paternal alcohol and family
      transition, after controlling for a wide range of confounding factors. RESULTS:
      Children whose fathers were moderate or heavy drinkers with at least weekly
      alcohol consumption showed 1.5-2.5 points lower mean IQ scores and greater
      behaviour problems (range 0.1-0.3 SD) compared with those whose fathers were
      light or infrequent drinkers. Compared with children from stable intact families,
      children who transitioned into stepfamilies had 1 point lower IQ and greater
      behaviour problems by 0.1-0.4 SD, and children from stable single-parent families
      or with transition into single-parent families showed no cognitive deficit but
      greater behaviour problems (range 0.1-0.3 SD). CONCLUSIONS: The sharp rise in
      both alcohol consumption and divorce/re-marriage rates in former Soviet countries
      may have negative consequences for cognitive and behavioural development in
      children.

PMID- 22586133
TI  - Commentary: iodine deficiency as a new challenge for industrialized countries: a
      UK perspective.

PMID- 22586134
TI  - Commentary: from iodine deficiency in Papua New Guinea to a global programme of
      prevention.

PMID- 22586135
TI  - Neurological damage to the fetus resulting from severe iodine deficiency during
      pregnancy.
AB  - Endemic cretinism is characterised by multiple neurological defects including
      deaf-mutism, diplegia, squint, and mental deficiency. The condition is widely
      prevalent in the Highlands of New Guinea in association with severe iodine
      deficiency. Previous studies have shown that iodised oil provides a very
      satisfactory correction of severe iodine deficiency in New Guinea. A controlled
      trial on the use of intramuscular iodised oil in the prevention of endemic
      cretinism was carried out in the Western Highlands of New Guinea and involved a
      population of approximately 8000. Subsequent follow-up over four years revealed
      26 endemic cretins out of a total of 534 children born to mothers who had not
      received iodised oil; the mothers of 5 of these cretins were pregnant at the
      start of the trial. In comparison, 7 cases of endemic cretinism occurred among
      498 children born to mothers who had been treated with iodised oil; in 6 of these
      7 cases, the mother was pregnant when the trial commenced. It is concluded that
      intramuscular iodised oil is effective in the prevention of endemic cretinism and
      that, for it to be effective, it should be given prior to conception. This
      suggests that severe iodine deficiency in the mother produces neurological damage
      during fetal development.

PMID- 22586136
TI  - Commentary: epidemiology, iodine deficiency and the power of multidisciplinary
      sufficiency.

PMID- 22586137
TI  - Commentary: from iodine deficiency to anomalous fetal development.

PMID- 22586138
TI  - Functional network connectivity underlying food processing: disturbed salience
      and visual processing in overweight and obese adults.
AB  - In order to adequately explore the neurobiological basis of eating behavior of
      humans and their changes with body weight, interactions between brain areas or
      networks need to be investigated. In the current functional magnetic resonance
      imaging study, we examined the modulating effects of stimulus category (food vs.
      nonfood), caloric content of food, and body weight on the time course and
      functional connectivity of 5 brain networks by means of independent component
      analysis in healthy lean and overweight/obese adults. These functional networks
      included motor sensory, default-mode, extrastriate visual, temporal visual
      association, and salience networks. We found an extensive modulation elicited by
      food stimuli in the 2 visual and salience networks, with a dissociable pattern in
      the time course and functional connectivity between lean and overweight/obese
      subjects. Specifically, only in lean subjects, the temporal visual association
      network was modulated by the stimulus category and the salience network by
      caloric content, whereas overweight and obese subjects showed a generalized
      augmented response in the salience network. Furthermore, overweight/obese
      subjects showed changes in functional connectivity in networks important for
      object recognition, motivational salience, and executive control. These
      alterations could potentially lead to top-down deficiencies driving the
      overconsumption of food in the obese population.

PMID- 22586139
TI  - Coevolution of gyral folding and structural connection patterns in primate
      brains.
AB  - Both cortical folding and structural connection patterns are more elaborated
      during the evolution of primate neocortex. For instance, cortical gyral shapes
      and structural connection patterns in humans are more complex and variable than
      those in chimpanzees and macaques. However, the intrinsic relationship between
      gyral folding and structural connection and their coevolution patterns across
      primates remain unclear. Here, our qualitative and quantitative analyses of in
      vivo diffusion tensor imaging (DTI) and structural magnetic resonance imaging
      (MRI) data consistently demonstrate that structural fiber connection patterns
      closely follow gyral folding patterns in the direction "tangent" to the cortical
      sphere, and this close relationship is well preserved in the neocortices of
      macaque, chimpanzee, and human brains, despite the progressively increasing
      complexity and variability of cortical folding and structural connection
      patterns. The findings suggest a hypothesis that a common axonal fiber pushing
      mechanism sculpts the curved patterns of gyri in the tangent direction during
      primate brain evolution. Our DTI/MRI data analysis provides novel insights into
      the structural architecture of primate brains, a new viewpoint of the
      relationship between cortical morphology and connection, and a basis for future
      elucidation of the functional implication of coevolution of cortical folding and
      structural connection patterns.

PMID- 22586141
TI  - The process of implementation of the diabetes register in Primary Health Care.
AB  - QUALITY PROBLEM OR ISSUE: According to Swedish law, all health care units must
      have a system for quality improvement. The aim of this study was to follow an
      implementation process of a uniform routine for quality control of diabetes care
      in Primary Health Care in one county. INITIAL ASSESSMENT: Primary Health Care had
      a decentralized organization and patients with type 2 diabetes were served at 42
      different Primary Health Care Centres. CHOICE OF SOLUTION: As the Swedish
      Diabetes Register (National Diabetes Register, NDR) holds the most important
      quality indicators, implementation of the NDR registration at all centres was
      chosen to be the best way to follow up quality in diabetes care. IMPLEMENTATION:
      The process of implementing the NDR went through different phases and the main
      way to encourage commitment to the process was to reward performance in a
      progressively more differentiated way. EVALUATION: During the implementation
      process (2001-05) there was an increasing rate of registration. When the
      programme ceased, the registration rate had reached a level of 75%, which has
      remained stable and was still in 2010 one of the highest rates in Sweden. LESSONS
      LEARNED: Important factors for success were the initiative taken by the
      profession itself and strong support from the leaders of the county council. It
      was also important to let the process develop gradually in order to get all staff
      involved. Among the outcomes was an increase in computer use in clinical practice
      among the diabetes nurse specialists and a structured way of encouraging the
      patients' participation in self-care.

PMID- 22586140
TI  - The ups and downs of the posteromedial cortex: age- and amyloid-related
      functional alterations of the encoding/retrieval flip in cognitively normal older
      adults.
AB  - Neural networks supporting memory function decline with increasing age.
      Accumulation of amyloid-beta, a histopathological finding in Alzheimer's disease,
      is a likely contributor. Posteromedial cortices (PMCs) are particularly
      vulnerable to early amyloid pathology and play a role in both encoding and
      retrieval processes. The extent to which aging and amyloid influence the ability
      to modulate activity between these processes within the PMC was investigated by
      combining positron emission tomography-amyloid imaging with functional magnetic
      resonance imaging in cognitively normal older and young adults. Young subjects
      exhibited a marked decrease in activity during encoding and an increase during
      retrieval (also known as encoding/retrieval "flip"). Impaired ability to modulate
      activity was associated with increasing age, greater amyloid burden, and worse
      memory performance. In contrast, the hippocampus showed increased activity during
      both encoding and retrieval, which was not related to these variables. These
      findings support a specific link between amyloid pathology and neural dysfunction
      in PMC and elucidate the underpinnings of age-related memory dysfunction.

PMID- 22586142
TI  - Thyroid hormone and the central control of homeostasis.
AB  - It has long been known that thyroid hormone has profound direct effects on
      metabolism and cardiovascular function. More recently, it was shown that the
      hormone also modulates these systems by actions on the central autonomic control.
      Recent studies that either manipulated thyroid hormone signalling in anatomical
      areas of the brain or analysed seasonal models with an endogenous fluctuation in
      hypothalamic thyroid hormone levels revealed that the hormone controls energy
      turnover. However, most of these studies did not progress beyond the level of
      anatomical nuclei; thus, the neuronal substrates as well as the molecular
      mechanisms remain largely enigmatic. This review summarises the evidence for a
      role of thyroid hormone in the central autonomic control of peripheral
      homeostasis and advocates novel strategies to address thyroid hormone action in
      the brain on a cellular level.

PMID- 22586144
TI  - Molecular pathology and genetics of pancreatic endocrine tumours.
AB  - Pancreatic neuroendocrine tumours (PETs) are the second most frequent pancreatic
      neoplasms. Their poor chemosensitivity, high rate of metastatic disease and
      relatively long survival make PETs an ideal field to be explored for novel
      therapies based on specific molecular changes. PETs are generally sporadic but
      can also arise within hereditary syndromes, such as multiple endocrine neoplasia
      type 1, von Hippel-Lindau, neurofibromatosis type 1 and tuberous sclerosis
      complex, which represent a model for sporadic cases too. Among allelic
      imbalances, main genomic changes involve gain of 17q, 7q and 20q and loss of 11q,
      6q and 11p, which identify regions of putative candidate oncogenes or tumour
      suppressor genes (TSGs), respectively, sometime with potential prognostic
      significance. Overexpression of Src-like kinases and cyclin D1 (CCND1) oncogene
      has been described. As for TSGs, P53 (TP53), DPC4/SMAD4 and RB (RB1) are not
      implicated in PET tumorigenesis, while for p16INK4a (CDKN2A), TIMP3, RASSF1A and
      hMLH1, more data are available, suggesting a role for methylation as a silencing
      mechanism. In the last decade, gene expression profile studies, analysis of
      microRNAs and, more recently, large-scale mutational analysis have highlighted
      commonly altered molecular pathways in the pathology of PETs. The roles of the
      mammalian target of rapamycin pathway, and its connection with Src kinases, and
      the activity of a number of tyrosine kinase receptors seem to be pivotal, as
      confirmed by the results of recent clinical trials with targeted agents.
      Mutations of DAXX and ATRX are common and related to altered telomeres but not to
      prognosis.

PMID- 22586143
TI  - ADAM10 promotes pituitary adenoma cell migration by regulating cleavage of CD44
      and L1.
AB  - ADAM10 is a metalloproteinase that regulates invasiveness in many tumors. Here,
      we found that ADAM10 expression correlates with the invasiveness of pituitary
      adenomas and contributes to invasion by cleaving L1 and CD44. In high-grade
      pituitary adenoma patients, ADAM10 expression levels were found to be elevated
      compared with low-grade pituitary adenomas. In a phorbol 12-myristate 13-acetate
      (PMA)-stimulated pituitary adenoma cell line, AtT-20 cells, we found that the
      cleavage of L1 was correspondingly enhanced with the increased interaction
      between Src and Shc. Increases in PMA-induced L1 cleavage and the phosphorylation
      of residue 418 of Src (418Src) were promoted by overexpression of ADAM10.
      Inversely, knockdown of Adam10 suppressed PMA-induced L1 cleavage and the
      phosphorylation of Src, which was blocked by the Src inhibitor PP2 and the MEK
      inhibitor PD98059. On the other hand, calcium flux activation in AtT-20 cells
      resulted in increased CD44 cleavage, with reduction of the interaction between
      calmodulin and ADAM10. The induction of enhanced CD44 cleavage by calcium flux
      activation was inhibited by knockdown of Adam10. In addition, Adam10 knockdown
      repressed AtT-20 cell migration, which was reversed by CD44EXT (CD44 ectodomain
      cleavage). Collectively, these data indicated that ADAM10 facilitated cell
      migration through modulation of CD44 and L1 cleavage.

PMID- 22586145
TI  - Advances in preclinical SPECT instrumentation.
AB  - Preclinical SPECT of rodents is both in demand and very demanding. The need for
      high spatial resolution in combination with good sensitivity has given rise to
      considerable innovation in the areas of detectors, collimation, acquisition
      geometry, and image reconstruction. Some of the developments described herein are
      beginning to carry over into clinical imaging as well.

PMID- 22586146
TI  - Treadmill exercise inducing mild to moderate ischemia has no significant effect
      on skeletal muscle or cardiac 18F-FDG uptake and image quality on subsequent
      whole-body PET scan.
AB  - We report the effects of treadmill exercise on (18)F-FDG uptake in skeletal
      muscles and image quality of torso PET and compare stress myocardial perfusion
      imaging patterns with myocardial (18)F-FDG uptake. There were 3 groups of
      patients: 48 patients underwent PET within 8 h after a treadmill test (Ex 8), 45
      patients within 48 h after a treadmill test (Ex 48), and 34 patients without
      prior exercise. Mean workload (8.4 +/- 2.3 [Ex 8] vs. 8.9 +/- 2.6 metabolic
      equivalents [Ex 48]) was similar in both exercise groups. Muscle uptake was
      assessed by standardized uptake value. Myocardial uptake patterns were compared
      visually. Minor differences between patient groups were noted only for maximum
      standardized uptake value in quadriceps muscles. There was no correlation between
      perfusion defects and myocardial (18)F-FDG uptake patterns. Thus, treadmill
      exercise does not affect muscle (18)F-FDG uptake or image quality on subsequent
      PET. Cardiac (18)F-FDG uptake on torso PET scans is unrelated to myocardial
      perfusion status.

PMID- 22586147
TI  - Tumor targeting using affibody molecules: interplay of affinity, target
      expression level, and binding site composition.
AB  - Radionuclide imaging of cancer-associated molecular alterations may contribute to
      patient stratification for targeting therapy. Scaffold high-affinity proteins,
      such as Affibody molecules, are a new, promising class of probes for in vivo
      imaging. METHODS: The effects of human epidermal growth factor receptor 2 (HER2)
      affinity and binding site composition of HER2-binding Affibody molecules, and of
      the HER2 density on the tumor targeting, were studied in vivo. The tumor uptake
      and tumor-to-organ ratios of Affibody molecules with moderate (dissociation
      constant [K(D)] = 10(-9) M) or high (K(D) = 10(-10) M) affinity were compared
      between tumor xenografts with a high (SKOV-3) and low (LS174T) HER2 expression
      level in BALB/C nu/nu mice. Two Affibody molecules with similar affinity (K(D) =
      10(-10) M) but having alternative amino acids in the binding site were compared.
      RESULTS: In SKOV-3 xenografts, uptake was independent of affinity at 4 h after
      injection, but high-affinity binders provided 2-fold-higher tumor radioactivity
      retention at 24 h. In LS174T xenografts, uptake of high-affinity probes was
      already severalfold higher at 4 h after injection, and the difference was
      increased at 24 h. The clearance rate and tumor-to-organ ratios were influenced
      by the amino acid composition of the binding surface of the tracer protein.
      CONCLUSION: The optimal affinity of HER2-binding Affibody molecules depends on
      the expression of a molecular target. At a high expression level (>10(6)
      receptors per cell), an affinity in the low-nanomolar range is sufficient. At
      moderate expression, subnanomolar affinity is desirable. The binding site
      composition can influence the imaging contrast. This information may be useful
      for development of imaging agents based on scaffold affinity proteins.

PMID- 22586148
TI  - Republished: Simulation training improves ability to manage medical emergencies.
AB  - OBJECTIVE: In the case of an emergency, fast and structured patient management is
      crucial for a patient's outcome. Every physician and graduate medical student
      should possess basic knowledge of emergency care and the skills to manage common
      emergencies. This study determines the effect of a simulation-based curriculum in
      emergency medicine on students' abilities to manage emergency situations.
      METHODS: A controlled, blinded educational trial of 44 final-year medical
      students was carried out at Frankfurt Medical School; 22 students completed the
      former curriculum as the control group and 22 the new curriculum as the
      intervention group. The intervention consists of simulation-based training with
      theoretical and simulation-based training sessions in realistic encounters based
      on the Basic Life Support (BLS), Advanced Cardiac Life Support (ACLS) and adapted
      Advanced Trauma Life Support (ATLS) training. Further common emergencies were
      integrated corresponding to the course objectives. All students faced a
      performance-based assessment in a 10 station Objective Structured Clinical
      Examination (OSCE) using checklist rating within a maximum of 4 months after
      completion of the intervention. RESULTS: The intervention group performed
      significantly better at all of the 10 OSCE stations in the checklist rating
      (p<0.0001 to p=0.016). CONCLUSIONS: The simulation-based intervention offers a
      positively evaluated possibility to enhance students' skills in recognising and
      handling emergencies. Additional studies are required to measure the long-term
      retention of the acquired skills, as well as the effect of training in healthcare
      professionals.

PMID- 22586149
TI  - Republished: Sensitive troponin assays.
AB  - Sensitive troponin assays have been developed to meet the diagnostic goals set by
      the universal definition of myocardial infarction (MI). The analytical advantages
      of sensitive troponin assays include improved analytical imprecision at
      concentrations below the 99th percentile and the ability to define a reference
      distribution fully. Clinically, the improved sensitivity translates into the
      ability to diagnosis MI earlier, possibly within 3 h from admission and the
      ability to use the rate of change of troponin (Delta troponin) for diagnosis.
      Very sensitive assays may, in appropriately selected populations (perhaps with
      the addition of Delta troponin), allow diagnosis on hospital admission or within
      1-2 h of admission. An elevated troponin level occurring in patients without
      suspected acute coronary syndromes has, in all studies to date in which outcome
      has been examined, been shown to indicate an adverse prognosis whatever the
      underlying clinical diagnosis. Failure of elevation means a good prognosis
      allowing early, safe hospital discharge, whereas a raised value requires
      investigation and should help prevent clinically significant pathology being
      overlooked. Sensitive troponins do present a challenge to the laboratory and the
      clinician. For the laboratory, the diagnosis of MI requires a change in troponin
      value. For the clinician, the challenge is to shift from a simplistic yes/no
      diagnosis of MI based on a single troponin value to a diagnosis that utilises
      early troponin changes as part of the clinical picture, and to relate the new
      class of detectable troponin elevation in patients with ischaemic myocardial
      disease to existing clinical guidelines and trial evidence.

PMID- 22586150
TI  - Republished: Improving hand hygiene in a paediatric hospital: a multimodal
      quality improvement approach.
AB  - BACKGROUND: Effective hand hygiene has long been recognised as an important way
      to reduce the transmission of bacterial and viral pathogens in healthcare
      settings. However, many studies have shown that adherence to hand hygiene remains
      low, and improvement efforts have often not delivered sustainable results. The
      Children's Hospital at Westmead is the largest tertiary paediatric hospital in
      Sydney, Australia. The hospital participated in a state-wide 'Clean hands save
      lives' campaign which was initiated in 2006. INTERVENTION: Strong leadership,
      good stakeholder engagement, readily accessible alcohol-based hand rub at the
      point of patient care, a multifaceted education programme, monitoring of staff,
      adherence to recommended hand hygiene practices and contemporaneous feedback of
      performance data have significantly improved and maintained compliance with hand
      hygiene. RESULTS: Hand hygiene compliance has increased from 23% in 2006 to 87%
      in 2011 (p<0.001). Sustained improvement in compliance with hand hygiene has been
      evident in the last 4 years. A decline in a set of hospital-acquired infections
      (including rotavirus, multiresistant organism transmission, and nosocomial
      bacteraemia) has also been noted as hand hygiene rates have improved. Monthly
      usage of alcohol-based hand rub has increased from 16 litres/1000 bed days to 51
      litres/1000 bed days during this same period. CONCLUSION: This project has
      delivered sustained improvement in hand hygiene compliance by establishing a
      framework of multimodal evidence-based strategies.

PMID- 22586151
TI  - Retraction. Attitudes of preclinical medical students towards caring for
      chronically ill and dying patients: does palliative care teaching make a
      difference?

PMID- 22586152
TI  - Commentary: understanding risk behavior among adolescent cancer survivors--are
      they more like healthy adolescents or is cancer a teachable moment? A commentary
      on Klosky and colleagues' article on health behaviors in survivors of childhood
      cancer and their siblings.

PMID- 22586153
TI  - Engineering of the catalytic site of xylose isomerase to enhance bioconversion of
      a non-preferential substrate.
AB  - Mutation in active site would either completely eliminate enzyme activity or may
      result in an active site with altered substrate-binding properties. The enzyme
      xylose isomerase (XI) is sterospecific for the alpha-pyranose and alpha
      fructofuranose anomers and metal ions (M1 and M2) play a pivotal role in the
      catalytic action of this enzyme. Mutations were created at the M2 site of XI of
      Thermus thermophilus by replacing D254 and D256 with arginine. Mutants D254R and
      a double mutant (D254R/D256R) showed complete loss of activity while D256R showed
      an increase in the specificity on D-lyxose, L-arabinose and D-mannose which are
      non-preferential substrates for XI. Both wild type (WT) and D256R showed higher
      activity at pH 7.0 and 85 degrees C with an increase in metal requirement. The
      catalytic efficiency Kcat/Km (S(-1) mM(-1)) of D256R for D-lyxose, L-arabinose
      and D-mannose were 0.17, 0.09 and 0.15 which are higher than WT XI of
      T.thermophilus. The altered catalytic activity for D256R could be explained by
      the possible role of arginine in catalytic reaction or the changes in a substrate
      orientation site. However, both the theories are only assumptions and have to be
      addressed with crystal study of D256R.

PMID- 22586154
TI  - Towards a universal disulphide stabilised single chain Fv format: importance of
      interchain disulphide bond location and vL-vH orientation.
AB  - Engineered introduction of interface interchain disulphide bonds is perceived to
      be a simple method to increase the stability of single chain Fv (scFv). Six
      disulphide bond locations have been cited within the literature but the potential
      for the broad use of each has not been examined. Five of these disulphide bond
      locations were introduced into one scFv in order to compare their relative
      effects on expression, thermal stability, percent monomer formation and retention
      of antigen binding. The disulphide bond position vH44-vL100 was observed to
      enable the most favourable balance of biophysical properties. The vH44-vL100
      disulphide bond was introduced into five additional scFv in both vL-vH and vH-vL
      orientations in order to investigate its general applicability. Data are
      presented to show the relative influence of scFv sequence, v-region organisation
      and interchain disulphide bond on expression yield, thermal stability and percent
      monomer. Introduction of the vH44-vL100 disulphide bond typically resulted in no
      or little increase in thermal stability and no change in percent monomer but did
      confer the benefit of permanently fixing monomer:dimer ratios during purification
      and analysis.

PMID- 22586156
TI  - National survey of patient doses from whole-body FDG PET-CT examinations in
      France in 2011.
AB  - A national survey of patient doses from 'whole-body PET-CT' examinations was
      conducted within all French nuclear medicine departments in 2011. Data related to
      injected [(18)F]-fluorodeoxyglucose (FDG) activity and to computerised tomography
      (CT) parameters were received from 56 positron emission tomography (PET)-CT units
      (answer rate: ~60 %). The average specific injected FDG activity was equal to 4.3
      MBq kg(-1), in agreement with European recommendations. The new 'time-of-flight'
      technology enabled to decreasing the specific activity down to 3.5 MBq kg(-1).
      The results have shown that current diagnostic reference levels (DRLs) for the
      diagnostic trunk CT are too high for CT combined with PET, only performed in
      France for attenuation correction and localisation, and not for diagnostic
      purpose. Despite wide variations between PET-CT units (4-fold factor in
      CTDI(vol)), DRLs equal to 8 mGy (CTDI(vol)) and 750 mGy cm (dose-length product)
      could be proposed for whole-body PET-CT. The average effective dose related to
      whole-body PET-CT examination in France has been assessed to ~14 mSv.

PMID- 22586155
TI  - tRNAomics: tRNA gene copy number variation and codon use provide bioinformatic
      evidence of a new anticodon:codon wobble pair in a eukaryote.
AB  - tRNA genes are interspersed throughout eukaryotic DNA, contributing to genome
      architecture and evolution in addition to translation of the transcriptome. Codon
      use correlates with tRNA gene copy number in noncomplex organisms including
      yeasts. Synonymous codons impact translation with various outcomes, dependent on
      relative tRNA abundances. Availability of whole-genome sequences allowed us to
      examine tRNA gene copy number variation (tgCNV) and codon use in four
      Schizosaccharomyces species and Saccharomyces cerevisiae. tRNA gene numbers vary
      from 171 to 322 in the four Schizosaccharomyces despite very high similarity in
      other features of their genomes. In addition, we performed whole-genome
      sequencing of several related laboratory strains of Schizosaccharomyces pombe and
      found tgCNV at a cluster of tRNA genes. We examined for the first time effects of
      wobble rules on correlation of tRNA gene number and codon use and showed
      improvement for S. cerevisiae and three of the Schizosaccharomyces species. In
      contrast, correlation in Schizosaccharomyces japonicus is poor due to markedly
      divergent tRNA gene content, and much worsened by the wobble rules. In japonicus,
      some tRNA iso-acceptor genes are absent and others are greatly reduced relative
      to the other yeasts, while genes for synonymous wobble iso-acceptors are
      amplified, indicating wobble use not apparent in any other eukaryote. We
      identified a subset of japonicus-specific wobbles that improves correlation of
      codon use and tRNA gene content in japonicus. We conclude that tgCNV is high
      among Schizo species and occurs in related laboratory strains of S. pombe (and
      expectedly other species), and tRNAome-codon analyses can provide insight into
      species-specific wobble decoding.

PMID- 22586157
TI  - Clinical and pathological significance of interleukin 6 overexpression in
      systemic sclerosis.
AB  - OBJECTIVE: To determine the potential clinical and pathological significance of
      altered expression of interleukin 6 (IL-6) in systemic sclerosis (SSc). METHODS:
      Serum IL-6 and soluble IL-6 receptor levels were measured in patients with SSc
      (n=68) and healthy controls (n=15). Associations between serum IL-6 level and C
      reactive protein, platelet count and key clinical outcomes in SSc were explored.
      Expression of IL-6 in skin biopsies was also examined and western blot and
      reverse transcription PCRanalysis were performed using cultured dermal
      fibroblasts. The effect of IL-6 trans-signalling on production of extracellular
      matrix proteins was assessed and downstream signalling pathways were examined
      using pharmacological inhibitors. RESULTS: Serum IL-6 level was frequently
      elevated in patients with SSc, particularly in those with diffuse cutaneous SSc
      (dcSSc) with thrombocytosis and elevated acute phase markers. Prominent
      expression in the skin was observed in dermal fibroblasts, mononuclear cells and
      endothelial cells in patients with early dcSSc. In vitro experiments supported a
      potent profibrotic effect of IL-6 trans-signalling via the JAK2/STAT3 and ERK
      pathways. High IL-6 expression early in dcSSc appears to be associated with more
      severe skin involvement at 3 years and worse long-term survival than in those
      without elevated IL-6 levels. CONCLUSION: Our results confirm the overexpression
      of IL-6 in dcSSc and support the potential of IL-6 as a surrogate marker for
      clinical outcome in this disease. The data also provide rationale for clinical
      studies targeting IL-6 trans-signalling as a potential antifibrotic therapy for
      SSc.

PMID- 22586158
TI  - Dyslipidaemia in patients with seropositive arthralgia predicts the development
      of arthritis.

PMID- 22586159
TI  - Parental history of lupus and rheumatoid arthritis and risk in offspring in a
      nationwide cohort study: does sex matter?
AB  - OBJECTIVES: To examine the familial risk of systemic lupus erythematosus (SLE)
      and rheumatoid arthritis (RA), including juvenile rheumatoid/idiopathic arthritis
      (JRA), in a population-based setting; and to determine whether patterns of
      transmission differ according to the sex of the parent or offspring, in order to
      provide insight into the potential impact of X-chromosomal factors on sex
      disparities in these autoimmune diseases. METHODS: A population-based cohort of
      parent-offspring triads from Denmark (1977-2010) was established. SLE and RA
      incidence rates among offspring were calculated, and Cox regression was performed
      to assess the sex-specific risk of disease in offspring according to maternal or
      paternal disease history. RESULTS: Among 3 513 817 parent-offspring triads, there
      were 1258 SLE cases among offspring (1095 female, 163 male) and 9118 cases of
      RA/JRA (6086 female, 3032 male). Among female offspring, SLE risk was nearly the
      same according to maternal (HR 14.1) or paternal (HR 14.5) history (p=NS);
      likewise among male offspring, risk according to maternal (HR 5.5) and paternal
      (no cases) history were similar (p=NS). For RA, all risk estimates were similar,
      regardless of the sex of the offspring or parent (HR 2.6-2.9; p=NS). CONCLUSIONS:
      The authors quantified the familial risk of SLE and RA in a nationwide cohort
      study. For both diseases, transmission was comparable among both female and male
      offspring of maternal and paternal cases. These data provide evidence at the
      population level that X-chromosomal factors do not play a major role in sex
      disparities associated with the risk of SLE and RA.

PMID- 22586160
TI  - Screening for latent tuberculosis infection: performance of tuberculin skin test
      and interferon-gamma release assays under real-life conditions.
AB  - OBJECTIVES: To characterise optimal screening strategies for latent tuberculosis
      infection (LTBI) prior to the initiation of anti-tumour necrosis factor therapy.
      METHODS: Patients in 62 German rheumatology centres were evaluated for LTBI. Each
      patient was screened with a tuberculin skin test (TST) and one form of an
      interferon-gamma release assay (IGRA), either TSPOT.TB (TSPOT) or Quantiferon TB
      Gold (QFT). RESULTS: A total of 1529 patients with rheumatological disease were
      tested with a TST, 844 with TSPOT and 685 with QFT. TST was positive in 11.3%
      (n=173). The prevalence of LTBI was 8.0% when defined as a positive TST and no
      previous Bacille Calmette-Guerin (BCG) vaccination and 7.9% when based on a
      positive IGRA. Combining both estimates increased the prevalence of LTBI to
      11.1%. Clinical risk factors for LTBI were found in 122 patients (34 with a
      history of prior TB, 81 close contacts and 27 with suggestive chest x-ray
      lesions). A compound risk factor (CRF) was defined as the presence of at least
      one of these three risk factors. Statistical analyses were conducted to examine
      the association between CRF and LTBI test outcomes. In multivariate analysis, TST
      was influenced by CRF (OR 6.2; CI 4.08 to 9.44, p<0.001) and BCG vaccination
      status (OR 2.9; CI 2.00 to 4.35, p<0.001). QFT and TSPOT were only influenced by
      CRF (QFT: OR 2.6; CI 1.15 to 5.98, p=0.021; TSPOT: OR 8.7; CI 4.83 to 15.82,
      p<0.001). ORs and the agreement of TST and IGRA test results varied by
      rheumatological disease. CONCLUSION: LTBI test results in an individual patient
      need to be considered in the context of prior BCG vaccination and clinical risk
      factors. In patient populations with low rates of TB incidence and BCG
      vaccination, the use of both TST and IGRA may maximise sensitivity in detecting
      LTBI but may also reduce specificity.

PMID- 22586161
TI  - Rituximab therapy for chronic periaortitis.

PMID- 22586162
TI  - Interleukin-6 receptor blockade induces limited repair of bone erosions in
      rheumatoid arthritis: a micro CT study.
AB  - INTRODUCTION: Interleukin-6 receptor (IL-6R) blockade improves the signs and
      symptoms of rheumatoid arthritis (RA) and retards bone damage. Whether IL-6R
      blockade allows repair of existing bone erosions is so far unclear. METHODS: This
      study examined bone erosions in the metacarpophalangeal joints of 20 patients
      receiving treatment with the IL-6R blocker tocilizumab using micro CT (uCT). The
      maximal width and depth of individual bone erosions was measured at baseline and
      after 1 year of treatment. RESULTS: 133 bone erosions were identified at baseline
      with a mean (+/-SD) size of 2.23+/-1.26 mm and depth of 2.16+/-1.50 mm.
      Distribution analysis showed predominant involvement of the second compared with
      the third and fourth metacarpophalangeal joints, the metacarpal heads compared
      with the phalangeal bases and the radial quadrants compared with all other
      surfaces. Repair of bone erosions during tocilizumab treatment was confined to
      those lesions showing sclerosis at baseline and/or at follow-up and those with a
      width larger than 1.6 mm. The mean decrease in width of sclerosed erosions was
      thus 0.14+/-0.05 mm (p=0.0086) and 0.20+/-0.08 mm (p=0.019) for sclerosing
      lesions after 1 year of treatment. CONCLUSIONS: Blockade of IL-6R by tocilizumab
      can induce limited repair in a subset of erosions, particularly in large lesions
      with sclerosis. Repair of erosions during tocilizumab treatment reflects the
      favourable impact of IL-6R blockade on local bone remodelling in patients with
      RA.

PMID- 22586163
TI  - Differential human leucocyte allele association between psoriasis and psoriatic
      arthritis: a family-based association study.
AB  - OBJECTIVE: A recent population-based study identified several HLA alleles as
      conferring a risk for psoriatic arthritis (PsA) among patients with psoriasis.
      The authors aimed to confirm these results using a family-based association
      study. METHODS: PsA probands, psoriasis probands and their first-degree family
      members were included. All participants were evaluated for the presence of
      psoriasis and inflammatory arthritis. HLA-B and -C genotyping was performed. The
      family-based association test was used to test for differences between PsA and
      psoriasis patients in transmission of candidate alleles from parents to
      offspring. RESULTS: A total of 178 PsA and 30 psoriasis probands and 561 first
      degree family members were analysed. The following HLA alleles were over
      transmitted to PsA compared with psoriasis: HLA-C*12 (p=0.005), HLA-B*38
      (p=0.04), HLA-B*39 (p=0.03), HLA-B*27 (p=0.002). CONCLUSIONS: HLA-B*27, HLA-B*38,
      HLA-B*39 and HLA-C*12 alleles are potential PsA-specific genetic markers among
      patients with psoriasis.

PMID- 22586166
TI  - Canakinumab in a patient with juvenile Behcet's syndrome with refractory eye
      disease.

PMID- 22586164
TI  - The rs1143679 (R77H) lupus associated variant of ITGAM (CD11b) impairs complement
      receptor 3 mediated functions in human monocytes.
AB  - OBJECTIVES: The rs1143679 variant of ITGAM, encoding the R77H variant of CD11b
      (part of complement receptor 3; CR3), is among the strongest genetic
      susceptibility effects in human systemic lupus erythematosus (SLE). The authors
      aimed to demonstrate R77H function in ex-vivo human cells. METHODS:
      Monocytes/monocyte-derived macrophages from healthy volunteers homozygous for
      either wild type (WT) or 77H CD11b were studied. The genotype-specific expression
      of CD11b, and CD11b activation using conformation-specific antibodies were
      measured. Genotype-specific differences in iC3b-mediated phagocytosis, adhesion
      to a range of ligands and the secretion of cytokines following CR3 ligation were
      studied. The functionality of R77H was confirmed by replicating findings in COS7
      cells expressing variant-specific CD11b. RESULTS: No genotype-specific difference
      in CD11b expression or in the expression of CD11b activation epitopes was
      observed. A 31% reduction was observed in the phagocytosis of iC3b opsonised
      sheep erythrocytes (sRBC(iC3b)) by 77H cells (p=0.003) and reduced adhesion to a
      range of ligands: notably a 24% reduction in adhesion to iC3b (p=0.014). In
      transfected COS7 cells, a 42% reduction was observed in phagocytosis by CD11b
      (77H)-expressing cells (p=0.004). A significant inhibition was seen in the
      release of Toll-like receptor 7/8-induced pro-inflammatory cytokines from WT
      monocytes when CR3 was pre-engaged using sRBC(iC3b), but no inhibition in 77H
      monocytes resulting in a significant difference between genotypes (interleukin
      (IL)-1beta p=0.030; IL-6 p=0.029; tumour necrosis factor alpha p=0.027).
      CONCLUSIONS: The R77H variant impairs a broad range of CR3 effector functions in
      human monocytes. This study discusses how perturbation of this pathway may
      predispose to SLE.

PMID- 22586165
TI  - Obesity and the risk of psoriatic arthritis: a population-based study.
AB  - BACKGROUND: Obesity is associated with an increased risk of psoriasis; however,
      its potential impact on the risk of psoriatic arthritis (PsA) remains unclear.
      OBJECTIVES: To evaluate the association between body mass index (BMI) and the
      risk of PsA among patients with psoriasis from the general population. METHODS:
      The authors conducted a cohort study using data from The Health Improvement
      Network, an electronic medical records database representative of the UK general
      population, collected between 1995 and 2010. The exposure of interest was the
      first BMI measured after psoriasis diagnosis and endpoints were incident cases of
      physician-diagnosed PsA. The authors estimated the RR of PsA after adjusting for
      age, sex, and histories of trauma, smoking and alcohol consumption. RESULTS:
      Among 75,395 individuals with psoriasis (43% male, mean follow-up of 5 years, and
      mean age of 52 years), 976 developed PsA (incidence rate, 26.5 per 10,000 person
      years). The PsA incidence rates increased with increasing BMI. Compared with
      psoriasis patients with BMI <25 kg/m(2), the RRs for developing PsA were 1.09
      (0.93-1.28) for BMIs from 25.0 to 29.9, 1.22 (1.02-1.47) for BMIs from 30.0 to
      34.9 and 1.48 (1.20-1.81) for BMIs >=35.0. In our secondary analysis among all
      individuals, regardless of psoriasis (~2 million), the corresponding multivariate
      RRs tended to be stronger (1.0, 1.17, 1.57, 1.96; p for trend <0.001).
      CONCLUSIONS: This general population study suggests that obesity is associated
      with an increased risk of incident PsA and supports the importance of weight
      reduction among psoriasis patients who often suffer from the metabolic syndrome
      and obesity.

PMID- 22586167
TI  - B cell or T cell-dominant recurrence after rituximab therapy in patients with
      SLE.

PMID- 22586168
TI  - Gene expression analysis reveals HBP1 as a key target for the osteoarthritis
      susceptibility locus that maps to chromosome 7q22.
AB  - OBJECTIVES: An osteoarthritis (OA) susceptibility locus has been mapped to
      chromosome 7q22, to a region of high-linkage disequilibrium encompassing six
      genes: PRKAR2B, HBP1, COG5, GPR22, DUS4L and BCAP29. The authors assessed whether
      these genes were subject to cis-acting regulatory polymorphisms that are active
      in joint tissues and which could contribute to the association signal. METHODS:
      Using joint tissues from 156 patients with OA, and control cartilage from 25
      patients who had neck of the femur fractures, the authors measured the overall
      gene expression by quantitative PCR and the allelic expression of the genes,
      using an assay that can distinguish mRNA output from each allele of a transcript
      single nucleotide polymorphism. RESULTS: Five of the genes were expressed in
      joint tissues, the exception being GPR22, which the authors could not detect. In
      OA cartilage compared with control cartilage, significantly reduced expression
      levels were observed for these five genes. Carriers of the OA-associated alleles
      showed a significant reduction in expression of HBP1 in cartilage (p=0.0002) and
      synovium (p=0.02), and of DUS4L in fat pad (p=0.04). HBP1 and DUS4L also
      demonstrated allelic expression imbalance across a range of different joint
      tissues, with carriers of the associated allele showing an HBP1 allelic
      expression imbalance profile that was significantly different from non-carriers
      (p=0.008). CONCLUSION: Cis-acting regulatory polymorphisms acting on HBP1
      contribute to the OA association signal at chromosome 7q22. HBP1 codes for a
      transcription factor and studies by the authors have enabled them to prioritise
      this gene for further investigation.

PMID- 22586169
TI  - Methotrexate reduces immunogenicity in adalimumab treated rheumatoid arthritis
      patients in a dose dependent manner.

PMID- 22586170
TI  - Who are the young professionals working in the field of rheumatology in Europe
      and what are their needs? An EMEUNET (EMerging EUlar NETwork) survey.

PMID- 22586171
TI  - Mesenchymal stem cells are conditionally therapeutic in preclinical models of
      rheumatoid arthritis.
AB  - OBJECTIVE: The role of mesenchymal stem cells (MSC) in experimental arthritis is
      undoubtedly conflicting. This study explored the effect of bone marrow-derived
      MSC in previously untested and pathogenetically different models of rheumatoid
      arthritis (RA). METHODS: MSC were tested both in an induced (adjuvant-induced)
      and a spontaneous (K/BxN) arthritis model. Arthritis was assessed clinically and
      histologically. The proliferation of splenocytes and fibroblast-like synoviocytes
      (FLS) in the presence of MSC was measured by radioactivity incorporation. Toll
      like receptor (TLR) expression was measured by real-time PCR. T-regulatory cell
      (Treg) frequency, T-cell apoptosis and cytokine secretion were monitored by flow
      cytometry. RESULTS: MSC, in vitro, strongly inhibited critical cell populations;
      splenocytes and FLS. In contrast, MSC proved ineffective in vivo, unless they
      were administered before disease onset, an effect implying that the inflammatory
      arthritic milieu potentially abrogates MSC immunomodulatory properties. In order
      to alleviate inflammation before MSC infusion, the authors administered, at
      arthritis onset, a short course with a proteasome inhibitor, bortezomib, whereas
      MSC were infused when established disease was expected. The bortezomib plus MSC
      group demonstrated a significantly decreased arthritis score over arthritic, MSC
      only, bortezomib-only groups, also confirmed by histology and
      immunohistochemistry. The bortezomib plus MSC combination restored TLR expression
      and Treg frequency in blood and normalised FLS and splenocyte proliferation,
      apoptosis and cytokine secretion. CONCLUSION: MSC lose their immunomodulatory
      properties when infused in the inflammatory micromilieu of autoimmune arthritis.
      Conditioning of the recipient with bortezomib alters the disease microenvironment
      enabling MSC to modulate arthritis. Should milieu limitations also operate in
      human disease, this approach could serve as a strategy to treat RA by MSC.

PMID- 22586172
TI  - Prognostic factors of survival in patients with non-infectious mixed
      cryoglobulinaemia vasculitis: data from 242 cases included in the CryoVas survey.
AB  - BACKGROUND: Data on the prognosis of non-infectious mixed cryoglobulinaemia
      vasculitis (CryoVas) in the era of hepatitis C virus screening are lacking.
      METHODS: The French multicentre and retrospective CryoVas survey included 242
      patients with non-infectious mixed CryoVas. Causes of death and prognostic
      factors of survival were assessed and a prognostic score was determined to
      predict survival at 5 years. RESULTS: After a median follow-up of 35 months, 42
      patients (17%) died. Causes of death were mainly serious infections (50%) and
      vasculitis flare (19%). One-, 2-, 5- and 10-year overall survival rates were 91%,
      89%, 79% and 65%, respectively. A prognostic score, the CryoVas score (CVS), for
      the prediction of survival at 5 years was devised. Pulmonary and gastrointestinal
      involvement, glomerular filtration rate <60 ml/min and age >65 years were
      independently associated with death. At 5 years the death rates were 2.6%, 13.1%,
      29.6% and 38.5% for a CVS of 0, 1, 2 and >=3, respectively. At 1 year the death
      rates were 0%, 3.2%, 18.5% and 30.8% for a CVS of 0, 1, 2 and >=3, respectively.
      The CVS was strongly correlated with the Five Factor Score (FFS) 2009, another
      prognostic score validated in primary necrotising vasculitis (r=0.82; p<0.0001).
      The area under the curve for the CVS was 0.74 compared with 0.67 for the FFS,
      indicating a better performance of the CVS (p=0.052). CONCLUSIONS: In patients
      with non-infectious mixed CryoVas, the main prognostic factors are age >65 years,
      pulmonary and gastrointestinal involvement and renal failure. A score including
      these variables is significantly associated with the prognosis.

PMID- 22586173
TI  - Canakinumab for acute gouty arthritis in patients with limited treatment options:
      results from two randomised, multicentre, active-controlled, double-blind trials
      and their initial extensions.
AB  - OBJECTIVES: Gouty arthritis patients for whom non-steroidal anti-inflammatory
      drugs and colchicine are inappropriate have limited treatment options.
      Canakinumab, an anti-interleukin-1beta monoclonal antibody, may be an option for
      such patients. The authors assessed the efficacy/safety of one dose of
      canakinumab 150 mg (n=230) or triamcinolone acetonide (TA) 40 mg (n=226) at
      baseline and upon a new flare in frequently flaring patients contraindicated for,
      intolerant of, or unresponsive to non-steroidal anti-inflammatory drugs and/or
      colchicine. Core study co-primary endpoints were pain intensity 72 h postdose (0
      100 mm visual analogue scale and time to first new flare. METHODS: Two 12-week
      randomised, multicentre, active-controlled, double-blind, parallel-group core
      studies with double-blind 12-week extensions (response in acute flare and in
      prevention of episodes of re-flare in gout (beta-RELIEVED and beta-RELIEVED-II)).
      RESULTS: 82.6% patients had comorbidities. Mean 72-h visual analogue scale pain
      score was lower with canakinumab (25.0 mm vs 35.7 mm; difference, -10.7 mm; 95%
      CI -15.4 to -6.0; p<0.0001), with significantly less physician-assessed
      tenderness and swelling (ORs=2.16 and 2.74; both p<=0.01) versus TA. Canakinumab
      significantly delayed time to first new flare, reduced the risk of new flares by
      62% versus TA (HR: 0.38; 95% CI 0.26 to 0.57) in the core studies and by 56% (HR:
      0.44; 95% CI 0.32 to 0.60; both p<=0.0001) over the entire 24-week period, and
      decreased median C-reactive protein levels (p<=0.0001 at 72 h and 7 days). Over
      the 24-week period, adverse events were reported in 66.2% (canakinumab) and 52.8%
      (TA) and serious adverse events were reported in 8.0% (canakinumab) and 3.5% (TA)
      of patients. Adverse events reported more frequently with canakinumab included
      infections, low neutrophil count and low platelet count. CONCLUSION: Canakinumab
      provided significant pain and inflammation relief and reduced the risk of new
      flares in these patients with acute gouty arthritis.

PMID- 22586174
TI  - Descriptions of spinal MRI lesions and definition of a positive MRI of the spine
      in axial spondyloarthritis: a consensual approach by the ASAS/OMERACT MRI study
      group.
AB  - OBJECTIVE: The aim of this study was to define characteristic MRI findings in the
      spine of patients with axial spondyloarthritis (SpA) and provide a definition of
      a positive spinal MRI for inflammation and structural changes. METHODS: Technical
      details of spinal MRI and the description of spinal lesions of both inflammation
      and structural changes were discussed in consecutive meetings of 10 experts of
      the Assessment in SpondyloArthritis international Society (ASAS). The discussions
      aimed at a broad consensus on definitions of 'a positive spinal MRI' for both
      types of lesions and were backed up by a systematic literature search. RESULTS: A
      total of six different types of lesions were described for inflammation-
      anterior/posterior spondylitis, spondylodiscitis, arthritis of costovertebral
      joints, arthritis of zygoapophyseal joints and enthesitis of spinal ligaments-
      and another four for structural changes--fatty deposition, erosions,
      syndesmophytes and ankylosis. In the literature review, four relevant papers were
      identified. Anterior/posterior spondylitis and fat depositions at vertebral edges
      were considered as the most typical findings in SpA. Based on expert consensus
      and taking the literature review into consideration, a positive spinal MRI for
      inflammation was defined as the presence of anterior/posterior spondylitis in >=3
      sites. Evidence of fatty deposition at several vertebral corners was found to be
      suggestive of axial SpA, especially in younger adults. ASAS members (n=56)
      approved these definitions by voting in January 2010. CONCLUSIONS: This consensus
      statement gives clear descriptions of disease-related spinal lesions and of
      definitions of a positive spinal MRI for inflammatory lesions (spondylitis) and
      structural changes (fat deposition). These definitions can be used to describe
      findings of spinal MRI in patients with SpA in daily practice and clinical
      studies.

PMID- 22586175
TI  - Studying associations between variants in TRAF1-C5 and TNFAIP3-OLIG3 and the
      progression of joint destruction in rheumatoid arthritis in multiple cohorts.

PMID- 22586176
TI  - Childhood socioeconomic factors and perinatal characteristics influence
      development of rheumatoid arthritis in adulthood.
AB  - BACKGROUND: Rheumatoid arthritis (RA) has been associated with lower
      socioeconomic status (SES), but the reasons for this are not known. OBJECTIVE: To
      examine childhood SES measures, SES trajectory and other perinatal factors in
      relation to RA. METHODS: The sample included 50 884 women, aged 35-74 (84% non
      Hispanic white) enrolled 2004-9 in a US national cohort study. In baseline
      questionnaires, cases (N=424, 0.8%) reported RA diagnosis after age 16, ever use
      of disease-modifying antirheumatic drugs or steroids for RA and >=6 weeks
      bilateral joint swelling. Childhood SES measures are presented as OR and 95% CI
      adjusted for age and race/ethnicity. Analyses of perinatal factors also adjusted
      for childhood SES, and joint effects of childhood and adult SES and smoking
      exposures were evaluated. RESULTS: Patients with RA reported lower childhood
      household education (<12 years vs college degree; OR=1.7; 95% CI 1.1 to 2.5),
      food insecurity (OR=1.5, 95% CI 1.1 to 2.0) and young maternal age (<20 vs 20-34
      years; OR=1.7, 95% CI 1.2 to 2.5), with a trend (p<0.0001) for increasing number
      of adverse factors (OR=3.0; 95% CI 1.3 to 7.0; 4 vs 0 factors) compared with non
      cases. Low birth weight (<2500 g) [corrected] and preconception paternal smoking
      were independently associated with RA. Together, lower childhood SES and adult
      education (<college degree) were associated with RA (interaction p=0.03), with a
      joint effect magnitude similar to a history of paternal and adult smoking.
      CONCLUSIONS: RA was associated with low childhood SES sustained into adulthood,
      with cumulative effects across multiple measures, suggesting the importance of
      other unmeasured factors linking SES and RA.

PMID- 22586177
TI  - Rituximab versus oral cyclophosphamide for treatment of relapses of proliferative
      lupus nephritis: a clinical observational study.

PMID- 22586178
TI  - HCS-Analyzer: open source software for high-content screening data correction and
      analysis.
AB  - MOTIVATION: High-throughput screening is a powerful technology principally used
      by pharmaceutical industries allowing the identification of molecules of interest
      within large libraries. Originally target based, cellular assays provide a way to
      test compounds (or other biological material such as small interfering RNA) in a
      more physiologically realistic in vitro environment. High-content screening (HCS)
      platforms are now available at lower cost, giving the opportunity for
      universities or research institutes to access those technologies for research
      purposes. However, the amount of information extracted from each experiment is
      multiplexed and hence difficult to handle. In such context, there is an important
      need for an easy-to-use, but still powerful software able to manage
      multidimensional screening data by performing adapted quality control and
      classification. HCS-analyzer includes: a user-friendly interface specifically
      dedicated to HCS readouts, an automated approach to identify systematic errors
      potentially occurring during screening and a set of tools to classify, cluster
      and identify phenotypes of interest among large and multivariate data.
      AVAILABILITY: The application, the C# .Net source code, as well as detailed
      documentation, are freely available at the following URL: http://hcs-analyzer.ip
      korea.org.

PMID- 22586179
TI  - Blindness-causing trachomatous trichiasis biomarkers sighted.

PMID- 22586180
TI  - Single nucleotide polymorphisms and outcome risk in unrelated mismatched
      hematopoietic stem cell transplantation: an exploration study.
AB  - Genetic risk factors contribute to adverse outcome of hematopoietic stem cell
      transplantation (HSCT). Mismatching of the HLA complex most strongly determines
      outcomes, whereas non-HLA genetic polymorphisms are also having an impact.
      Although the majority of HSCTs are mismatched, only few studies have investigated
      the effects of non-HLA polymorphisms in the unrelated HSCT and HLA-mismatched
      setting. To understand these effects, we genotyped 41 previously studied single
      nucleotide polymorphisms (SNPs) in 2 independent, large cohorts of HSCT donor
      recipient pairs (n = 460 and 462 pairs) from a homogeneous genetic background.
      The study population was chosen to pragmatically represent a large clinically
      homogeneous group (acute leukemia), allowing all degrees of HLA matching. The TNF
      1031 donor-recipient genotype mismatch association with acute GVHD grade 4 was
      the only consistent association identified. Analysis of a subgroup of higher HLA
      matching showed consistent associations of the recipient IL2-330 GT genotype with
      risk of chronic GVHD, and the donor CTLA4-CT60 GG genotype with protection from
      acute GVHD. These associations are strong candidates for prediction of risk in a
      clinical setting. This study shows that non-HLA gene polymorphisms are of
      relevance for predicting HSCT outcome, even for HLA mismatched transplants.

PMID- 22586182
TI  - Nonmyeloablative allogeneic transplantation with or without 90yttrium ibritumomab
      tiuxetan is potentially curative for relapsed follicular lymphoma: 12-year
      results.
AB  - In 2008, we reported favorable 5-year outcomes of nonmyeloablative allogeneic
      stem cell transplantation after fludarabine, cyclophosphamide, rituximab (FCR)
      conditioning for relapsed and chemosensitive follicular lymphoma. However,
      innovative strategies were still needed to treat patients with chemorefractory
      disease. We therefore subsequently performed a trial in which (90)Y-ibritumomab
      tiuxetan (0.4 mCi/kg) was added to the fludarabine, cyclophosphamide conditioning
      regimen ((90)YFC). Here, we report updated results of the FCR trial and outcomes
      after (90)YFC. For the FCR group (N = 47), since the last update, one patient
      developed recurrent disease. With a median follow-up of 107 months (range, 72-142
      months), the 11-year overall survival and progression-free survival rates were
      78%, and 72%, respectively. For the (90)YFC group (N = 26), more patients had
      chemorefractory disease than did those in the FCR group (38% and 0%, P < .001).
      With a median follow-up of 33 months (range,17-94 months), the 3-year progression
      free survival rates for patients with chemorefractory and chemosensitive disease
      were 80% and 87%, respectively (P = .7). The low frequency of relapse observed
      after a long follow-up interval of 9 years in the FCR group suggests that these
      patients are cured of their disease. The addition of (90)Y to the conditioning
      regimen appears to be effective in patients with chemorefractory disease. This
      trial was registered at www.clinicaltrials.gov as NCT00048737.

PMID- 22586181
TI  - The COPII pathway and hematologic disease.
AB  - Multiple diseases, hematologic and nonhematologic, result from defects in the
      early secretory pathway. Congenital dyserythropoietic anemia type II (CDAII) and
      combined deficiency of coagulation factors V and VIII (F5F8D) are the 2 known
      hematologic diseases that result from defects in the endoplasmic reticulum (ER)
      to-Golgi transport system. CDAII is caused by mutations in the SEC23B gene, which
      encodes a core component of the coat protein complex II (COPII). F5F8D results
      from mutations in either LMAN1 (lectin mannose-binding protein 1) or MCFD2
      (multiple coagulation factor deficiency protein 2), which encode the ER cargo
      receptor complex LMAN1-MCFD2. These diseases and their molecular pathogenesis are
      the focus of this review.

PMID- 22586183
TI  - Multiple SNP testing improves risk prediction of first venous thrombosis.
AB  - There are no risk models available yet that accurately predict a person's risk
      for developing venous thrombosis. Our aim was therefore to explore whether
      inclusion of established thrombosis-associated single nucleotide polymorphisms
      (SNPs) in a venous thrombosis risk model improves the risk prediction. We
      calculated genetic risk scores by counting risk-increasing alleles from 31 venous
      thrombosis-associated SNPs for subjects of a large case-control study, including
      2712 patients and 4634 controls (Multiple Environmental and Genetic Assessment).
      Genetic risk scores based on all 31 SNPs or on the 5 most strongly associated
      SNPs performed similarly (areas under receiver-operating characteristic curves
      [AUCs] of 0.70 and 0.69, respectively). For the 5-SNP risk score, the odds ratios
      for venous thrombosis ranged from 0.37 (95% confidence interval [CI], 0.25-0.53)
      for persons with 0 risk alleles to 7.48 (95% CI, 4.49-12.46) for persons with
      more than or equal to 6 risk alleles. The AUC of a risk model based on known
      nongenetic risk factors was 0.77 (95% CI, 0.76-0.78). Combining the nongenetic
      and genetic risk models improved the AUC to 0.82 (95% CI, 0.81-0.83), indicating
      good diagnostic accuracy. To become clinically useful, subgroups of high-risk
      persons must be identified in whom genetic profiling will also be cost-effective.

PMID- 22586184
TI  - Should we stop telling obese patients to lose weight?

PMID- 22586186
TI  - Is the treatment of obesity futile?: NO.

PMID- 22586185
TI  - Is the treatment of obesity futile?: YES.

PMID- 22586188
TI  - I go to my minister to pray.

PMID- 22586189
TI  - Religiosity in primary care.

PMID- 22586190
TI  - On-target article.

PMID- 22586192
TI  - The downside of weight loss: realistic intervention in body-weight trajectory.
AB  - OBJECTIVE: To explore the reasons why long-term weight loss is seldom achieved
      and to evaluate the consequences of various weight trajectories, including
      stability, loss, and gain. QUALITY OF EVIDENCE: Studies evaluating population
      weight metrics were mainly observational. Level I evidence was available to
      evaluate the influence of weight interventions on mortality and quality of life.
      MAIN MESSAGE: Sustained weight loss is achieved by a small percentage of those
      intending to lose weight. Mortality is lowest in the high-normal and overweight
      range. The safest body-size trajectory is stable weight with optimization of
      physical and metabolic fitness. With weight loss there is evidence for lower
      mortality in those with obesity-related comorbidities. There is also evidence for
      improved health-related quality of life in obese individuals who lose weight.
      Weight loss in the healthy obese, however, is associated with increased
      mortality. CONCLUSION: Weight loss is advisable only for those with obesity
      related comorbidities. Healthy obese people wishing to lose weight should be
      informed that there might be associated risks. A strategy that leads to a stable
      body mass index with optimized physical and metabolic fitness at any size is the
      safest weight intervention option.

PMID- 22586194
TI  - Unplanned pregnancy in a woman with Crohn disease.

PMID- 22586193
TI  - Smoking cessation therapy during pregnancy.
AB  - QUESTION: Despite being highly motivated to quit, many of my patients struggle
      with smoking cessation during pregnancy. Can you comment on the current treatment
      options and discuss their safety and efficacy during pregnancy? ANSWER: Given the
      considerable and well-documented adverse effects of antenatal smoking on mother
      and fetus, pharmacotherapy for smoking cessation should be considered. Available
      medications include nicotine replacement therapy, sustained-release bupropion,
      and varenicline. Nicotine replacement therapy and bupropion do not appear to
      increase the risk of major malformations; however, there is currently limited
      evidence on the use of varenicline during pregnancy. Given that these agents are
      only marginally successful in smoking cessation, their use should always be
      accompanied by behavioural counseling and education to maximize quit rates.

PMID- 22586195
TI  - Physical activity in type 1 diabetes mellitus: assessing risks for physical
      activity clearance and prescription.

PMID- 22586196
TI  - Ophthaproblem. Can you identify this condition? Vernal keratoconjunctivitis with
      shield ulcers.

PMID- 22586197
TI  - Dermacase. Can you identify this condition? Eruptive xanthomas.

PMID- 22586199
TI  - Nutritional counseling in family medicine in 2010.

PMID- 22586198
TI  - Diabetes in the frail elderly: individualization of glycemic management.

PMID- 22586201
TI  - Transformative teachers.

PMID- 22586200
TI  - Emergency contraception: knowledge and attitudes of Nova Scotian family
      physicians.
AB  - OBJECTIVE: To determine the extent to which Nova Scotian FPs prescribe and
      provide emergency contraceptive pills (ECPs) and to explore their knowledge of
      and attitudes toward ECPs. DESIGN: Survey of Nova Scotian FPs using a modified
      Dillman method. SETTING: All regions of Nova Scotia. PARTICIPANTS: Family
      physicians registered with Dalhousie University's Division of Continuing Medical
      Education. MAIN OUTCOME MEASURES: Sex differences in the provision of ECPs and
      knowledge and attitudes about the ECP Plan B. RESULTS: Of 913 eligible FPs, 155
      (17.0%) participated in the survey. Respondents resembled the sampling frame
      closely. Most physicians (64.0%) had prescribed ECPs in the previous year (mean
      number of prescriptions, 4.92); only 12.9% provided ECPs in advance of need.
      Knowledge about Plan B was quite good, except for knowledge of the time frame for
      potential effectiveness; only 29.2% of respondents answered that question
      correctly. Respondents generally supported nonprescription availability of ECPs,
      but 25.0% of FPs were concerned that this could lead to less use of more
      effective methods of contraception, and 39.2% believed that it would encourage
      repeat use. Younger FPs provided ECPs more often than their older colleagues,
      while female respondents had better knowledge about Plan B. In multivariate
      analysis being younger than 40 years was marginally associated with prescribing
      Plan B and with prescribing any form of ECP. CONCLUSION: Most Nova Scotian FPs
      provided ECPs and had generally good knowledge about and attitudes toward
      providing such contraception without prescription. However, FPs were poorly
      informed about the length of time that Plan B can be effective, which could
      potentially affect use when patients consult several days after unprotected sex.
      There were some concerns about nonprescription availability of ECPs, which could
      have implications for recommending it to patients. Rarely were ECPs prescribed
      for advance use, which might represent a lost prevention opportunity, especially
      for adolescents who often do not use effective contraception.

PMID- 22586202
TI  - FMF: Canada's premier medical conference: November 15 to 17, 2012, in Toronto,
      Ont.

PMID- 22586203
TI  - Rebuttal: is the treatment of obesity futile?: YES.

PMID- 22586204
TI  - Rebuttal: Is the treatment of obesity futile?: NO.

PMID- 22586205
TI  - Practice and payment preferences of newly practising family physicians in British
      Columbia.
AB  - OBJECTIVE: To examine the remuneration model preferences of newly practising
      family physicians. DESIGN: Mixed-methods study comprising a cross-sectional, Web
      based survey, as well as qualitative content analysis of answers to open-ended
      questions. SETTING: British Columbia. PARTICIPANTS: University of British
      Columbia family practice residents who graduated between 2000 and 2009. MAIN
      OUTCOME MEASURES: Preferred remuneration models of newly practising physicians.
      RESULTS: The survey response rate was 31% (133 of 430). Of respondents, 71% (93
      of 132) preferred non-fee-for-service practice models and 86% (110 of 132)
      identified the payment model as very or somewhat important in their choice of
      future practice. Three principal themes were identified from content analysis of
      respondents' open-ended comments: frustrations with fee-for-service billing,
      which encompassed issues related to aggravations with "the business side of
      things" and was seen as impeding "the freedom to focus on medicine"; quality of
      patient care, which embraced the importance of a payment model that supported
      "comprehensive patient care" and "quality rather than quantity"; and freedom to
      choose, which supported the plurality of practice preferences among providers who
      strived to provide quality care for patients, "whatever model you happen to be
      working in." CONCLUSION: Newly practising physicians in British Columbia
      preferred alternatives to fee-for-service payment models, which were perceived as
      contributing to fewer frustrations with billing systems, improved quality of work
      life, and better quality of patient care.

PMID- 22586206
TI  - Practice recruitment.

PMID- 22586207
TI  - Evaluation of the 20% D-methamphetamine requirement for determining illicit use
      of methamphetamine in urine.
AB  - In urine drug testing, enantiomer analysis is used to determine whether a
      positive methamphetamine result could be due to use of an over-the-counter (OTC)
      nasal inhaler containing L-methamphetamine. D-methamphetamine at more than 20% of
      the total is considered indicative of a source other than an OTC product. This
      interpretation is based on a 1991 Department of Health and Human Services (HHS)
      Technical Advisory. We performed studies to verify the methamphetamine enantiomer
      content of current OTC nasal inhalers and to evaluate current laboratory testing
      capabilities. This study demonstrated that OTC inhalers contain less than 1% D
      methamphetamine. A proficiency testing (PT) set for HHS-certified laboratories
      performing methamphetamine enantiomer testing found D-methamphetamine percentages
      that were consistently 1 to 3% higher than theoretical due to optical impurity of
      the derivatizing reagent N-trifluoroacetyl-L-prolyl chloride (L-TPC). The PT
      results also demonstrate that laboratories can accurately determine 20% D
      methamphetamine in samples with total methamphetamine concentrations down to 250
      ng/mL. Based on these studies, the guideline of >20% D-methamphetamine is
      appropriate for interpreting results obtained using current laboratory methods.

PMID- 22586208
TI  - Analysis of first and second generation legal highs for synthetic cannabinoids
      and synthetic stimulants by ultra-performance liquid chromatography and time of
      flight mass spectrometry.
AB  - Various "legal high" products were tested for synthetic cannabinoids and
      synthetic stimulants to qualitatively determine the active ingredient(s). Ultra
      performance liquid chromatography with accurate mass time-of-flight mass
      spectrometry (UPLC-TOF) was used to monitor the non-biological specimens
      utilizing a customized panel of 65+ compounds comprised of synthetic
      cannabinoids, synthetic stimulants and other related drugs. Over the past year,
      the United States Drug Enforcement Agency has controlled five synthetic
      cannabinoid compounds (JWH-018, JWH-073, JWH-200, CP-47,497 and CP-47,497-C8) and
      three synthetic stimulant compounds (3,4-methylenedioxypyrovalerone, mephedrone
      and methylone) that were previously reported to be detected in these legal high
      products. Through our analyses of first and second generation products, it was
      shown that many of these banned substances are no longer used and have been
      replaced by other derivatives that are federally legal. Since enactment of the
      federal bans on synthetic cannabinoids and synthetic stimulants, 4.9% of the
      products analyzed at our facility contained at least one controlled substance.
      The remaining 95.1% of products contained only uncontrolled drugs. We demonstrate
      the UPLC-TOF methodology to be a powerful tool in the qualitative identification
      of these designer drugs, thus enabling a laboratory to keep current with the
      drugs that are being sold as these designer products.

PMID- 22586209
TI  - Medical, statistical, ethical and human rights considerations in the assessment
      of age in children and young people subject to immigration control.
AB  - BACKGROUND: Unprecedented changes in both the scale and the complexity of
      international migration have led to international concern and controversy over
      the assessment of age in children and young people subject to immigration control
      or seeking asylum who say they are children yet have no documents to prove their
      stated age. SOURCES OF DATA: The article reviews the existing evidence on the
      reliability of medical and non-medical techniques for the assessment of
      chronological age. AREAS OF AGREEMENT: There is evidence that radiography (X
      rays) of bones and teeth, which is increasingly relied upon by immigration
      authorities, is imprecise, unethical and potentially unlawful, and should not be
      used for age assessment. AREAS OF CONTROVERSY: Medical techniques including X
      rays continue to be relied upon in the absence of an alternative approach
      resulting in legal challenges and uncertainty for children and young people.
      AREAS TIMELY FOR DEVELOPING RESEARCH: Further work is needed to establish a
      process for age assessment based on a 'holistic' multi-disciplinary approach
      which focuses not on chronological age exclusively but rather on the needs of
      children and young people subject to immigration control.

PMID- 22586210
TI  - Implementing tobacco control policies.
AB  - INTRODUCTION OR BACKGROUND: Tobacco currently kills 6 million people each year,
      increasingly in the low- and middle-income countries, which will bear the
      economic brunt of this epidemic. Tobacco control takes health professionals to
      very new destinations, away from the traditional curative medical model to
      mastering the corridors of power, using the media, and political lobbying and
      advocacy. None of these skills is taught in medical schools. AREAS OF AGREEMENT:
      The magnitude and future expansion of the tobacco epidemic is beyond controversy,
      as is the fact that the economic costs of tobacco outweigh any benefits. The
      tools needed to reduce the epidemic are also known and accepted, and these are
      virtually identical in all countries. It only requires political will to
      implement these. GROWING POINTS: All countries should ratify and implement the
      WHO Framework Convention on Tobacco Control and commit adequate funding to
      counter this global pandemic. AREAS TIMELY FOR DEVELOPING RESEARCH: Action must
      be based on the science of epidemiology, prevalence, health effects, economic
      burden, success of action taken and tracking the tobacco industry.

PMID- 22586211
TI  - Simultaneous chromatic and luminance human electroretinogram responses.
AB  - The parallel processing of information forms an important organisational
      principle of the primate visual system. Here we describe experiments which use a
      novel chromatic-achromatic temporal compound stimulus to simultaneously identify
      colour and luminance specific signals in the human electroretinogram (ERG).
      Luminance and chromatic components are separated in the stimulus; the luminance
      modulation has twice the temporal frequency of the chromatic modulation. ERGs
      were recorded from four trichromatic and two dichromatic subjects (1 deuteranope
      and 1 protanope). At isoluminance, the fundamental (first harmonic) response was
      elicited by the chromatic component in the stimulus. The trichromatic ERGs
      possessed low-pass temporal tuning characteristics, reflecting the activity of
      parvocellular post-receptoral mechanisms. There was very little first harmonic
      response in the dichromats' ERGs. The second harmonic response was elicited by
      the luminance modulation in the compound stimulus and showed, in all subjects,
      band-pass temporal tuning characteristic of magnocellular activity. Thus it is
      possible to concurrently elicit ERG responses from the human retina which reflect
      processing in both chromatic and luminance pathways. As well as providing a clear
      demonstration of the parallel nature of chromatic and luminance processing in the
      human retina, the differences that exist between ERGs from trichromatic and
      dichromatic subjects point to the existence of interactions between afferent post
      receptoral pathways that are in operation from the earliest stages of visual
      processing.

PMID- 22586212
TI  - Positional circulatory control in the sleeping infant and toddler: role of the
      inner ear and arterial pulse pressure.
AB  - Heart rate (HR) and arterial blood pressure (BP) are rapidly and reflexively
      adjusted as body position and the force/direction of gravity alters. Anomalies in
      these mechanisms may predispose to circulatory failure during sleep. We analysed
      the development of two key reflexes involved by undertaking a longitudinal (birth
      1 year) comparison of instantaneous HR and BP changes evoked by abrupt upright,
      sideways or horizontal repositioning. Each manoeuvre triggered an identical rise
      in HR (tachycardia) followed by a slower rise in diastolic blood pressure
      (DBP)/systolic blood pressure (SBP) and variable pulse pressure (PP) change. We
      show that tachycardia is triggered by acceleration (vestibular) sensors located
      in the inner ear and slight changes in the pulsatile component of BP then signal
      to the arterial baroreceptors to reinforce or oppose these actions as needed. We
      also identified a PP anomaly in sleeping 1-year-olds of smokers that prematurely
      slows HR and is associated with mild positional hypotension. We conclude that
      positional circulatory compensation is initiated pre-emptively in a feed-forward
      manner and that feedback changes in vago-sympathetic drive to the heart (and
      perhaps blood vessels) by PP exert a slower but powerful modulating effect. An
      anomaly in either or both mechanisms may weaken positional compensation in some
      sleeping infants.

PMID- 22586213
TI  - ATP binding and cross-bridge detachment steps during full Ca2+ activation:
      comparison of myofibril and muscle fibre mechanics by sinusoidal analysis.
AB  - Single myofibrils 50-60 MUm length and 2-3 MUm diameter were isolated from rabbit
      psoas muscle fibres, and cross-bridge kinetics were studied by small
      perturbations of the length (~0.2%) over a range of 15 frequencies (1-250 Hz).
      The experiments were performed at 15?C in the presence of 0.05-10 mM MgATP, 8mM
      phosphate (Pi), 200 mM ionic strength with KAc (acetate), pCa 4.35-4.65, and pH
      7.0. Two exponential processes, B and C, were resolved in tension transients.
      Their apparent rate constants (2pib and 2pic) increased as the [MgATP] was raised
      from 0.05 mM to 1mM, and then reached saturation at [MgATP] >= 1. Given that
      these rate constants were similar (c/b ~1.7) at [Pi] >= 4 mM, they were combined
      to achieve an accurate estimate of the kinetic constants: their sum and product
      were analysed as functions of [MgATP]. These analyses yielded K1 =2.91 +/- 0.31
      mM -1, k2 =288 +/- 36 s-1, and k-2 =10 +/- 21 s-1 (+/-95% confidence limit, n =13
      preparations), based on the cross-bridge model: AM+ATP <-> (step 1) AM.ATP <->
      (step 2) A+M.ATP, where K1 is the ATP association constant (step 1), k2 is the
      rate constant of the cross-bridge detachment (step 2), and k-2 is the rate
      constant of its reversal step. These kinetic constants are respectively
      comparable to those observed in single fibres from rabbit psoas (K1 =2.35 +/-
      0.31 mM -1, k2 =243 +/- 22 s-1, and k-2 =6 +/- 14 s-1; n =8 preparations) when
      analysed by the same methods and under the same experimental conditions. These
      values are respectively not significantly different from those obtained in
      myofibrils, indicating that the same kinetic constants can be deduced from
      myofibril and muscle fibre studies, in terms of ATP binding and cross-bridge
      detachments steps. The fact that K1 in myofibrils is 1.2 times that in fibres
      (P~0.05) may be explained by a small concentration gradient of ATP, ADP and/or Pi
      in single fibres.

PMID- 22586214
TI  - Corticospinal reorganization after spinal cord injury.
AB  - The corticospinal tract (CST) is a major descending pathway contributing to the
      control of voluntary movement in mammals. During the last decades anatomical and
      electrophysiological studies have demonstrated significant reorganization in the
      CST after spinal cord injury (SCI) in animals and humans. In animal models of
      SCI, anatomical evidence showed corticospinal sprouts rostral and caudal to the
      lesion and their integration into intraspinal axonal circuits.
      Electrophysiological data suggested that indirect connections from the primary
      motor cortex to forelimb motoneurons, via brainstem nuclei and spinal cord
      interneurons, or direct connections from slow uninjured corticospinal axons,
      might contribute to the control of movement after a CST injury. In humans with
      SCI, post mortem spinal cord tissue revealed anatomical changes in the CST some
      of which were similar but others markedly different from those found in animal
      models of SCI. Human electrophysiological studies have provided ample evidence
      for corticospinal reorganization after SCI that may contribute to functional
      recovery. Together these studies have revealed a large plastic capacity of the
      CST after SCI. There is also a limited understanding of the relationship between
      anatomical and electrophysiological changes in the CST and control of movement
      after SCI. Increasing our knowledge of the role of CST plasticity in functional
      restoration after SCI may support the development of more effective repair
      strategies.

PMID- 22586215
TI  - Biomarkers of mitochondrial content in skeletal muscle of healthy young human
      subjects.
AB  - Skeletal muscle mitochondrial content varies extensively between human subjects.
      Biochemical measures of mitochondrial proteins, enzyme activities and lipids are
      often used as markers of mitochondrial content and muscle oxidative capacity
      (OXPHOS). The purpose of this study was to determine how closely associated these
      commonly used biochemical measures are to muscle mitochondrial content and
      OXPHOS. Sixteen young healthy male subjects were recruited for this study.
      Subjects completed a graded exercise test to determine maximal oxygen uptake
      (VO2peak) and muscle biopsies were obtained from the vastus lateralis.
      Mitochondrial content was determined using transmission electron microscopy
      imaging and OXPHOS was determined as the maximal coupled respiration in
      permeabilized fibres. Biomarkers of interest were citrate synthase (CS) activity,
      cardiolipin content, mitochondrial DNA content (mtDNA), complex I-V protein
      content, and complex I-IV activity. Spearman correlation coefficient tests and
      Lin's concordance tests were applied to assess the absolute and relative
      association between the markers and mitochondrial content or OXPHOS. Subjects had
      a large range of VO2peak (range 29.9-71.6ml min-1 kg-1) and mitochondrial content
      (4-15% of cell volume).Cardiolipin content showed the strongest association with
      mitochondrial content followed by CS and complex I activities. mtDNA was not
      related to mitochondrial content. Complex IV activity showed the strongest
      association with muscle oxidative capacity followed by complex II activity.We
      conclude that cardiolipin content, and CS and complex I activities are the
      biomarkers that exhibit the strongest association with mitochondrial content,
      while complex IV activity is strongly associated with OXPHOS capacity in human
      skeletal muscle.

PMID- 22586216
TI  - Orai1, STIM1, and their associating partners.
AB  - Store-operated Ca(2+) (SOC) entry is one of the major mechanisms to raise
      intracellular Ca(2+) concentration in non-excitable cells. Ca(2+)-release
      activated Ca(2+) (CRAC) channels are a subtype of SOC channels that are
      extensively characterized in immune cells. Identification of STIM1 as an
      endoplasmic reticulum Ca(2+) sensor and Orai1 as the pore subunit has
      dramatically advanced the molecular understanding of CRAC channels. Recent
      efforts have focused on understanding the physiological aspects of CRAC channels
      at an organism level using transgenic animal models and at a molecular level
      using electrophysiological and biochemical tools. In this review, we summarize
      our current understanding of the interacting partners of Orai and STIM proteins
      in the regulation of CRAC channel activity and other non-CRAC channel-related
      functions.

PMID- 22586217
TI  - Uteroplacental insufficiency programmes vascular dysfunction in non-pregnant
      rats: compensatory adaptations in pregnancy.
AB  - Intrauterine growth restriction is a risk factor for cardiovascular disease in
      adulthood. We have previously shown that intrauterine growth restriction caused
      by uteroplacental insufficiency programmes uterine vascular dysfunction and
      increased arterial stiffness in adult female rat offspring. The aim of this study
      was to investigate vascular adaptations in growth restricted female offspring
      when they in turn become pregnant. Uteroplacental insufficiency was induced in
      WKY rats by bilateral uterine vessel ligation (Restricted) or sham surgery
      (Control) on day 18 of pregnancy. F0 pregnant females delivered naturally at
      term. F1 Control and Restricted offspring were mated at 4 months of age and
      studied on day 20 of pregnancy. Age-matched non-pregnant F1 Control and
      Restricted females were also studied. Wire and pressure myography were used to
      test endothelial and smooth muscle function, and passive mechanical wall
      properties, respectively, in uterine, mesenteric, renal and femoral arteries of
      all four groups. Collagen and elastin fibres were quantified using polarized
      light microscopy and qRT-PCR. F1 Restricted females were born 10-15% lighter than
      Controls (P <0.05). Non-pregnant Restricted females had increased uterine and
      renal artery stiffness compared with Controls (P <0.05), but this difference was
      abolished at day 20 of pregnancy. Vascular smooth muscle and endothelial function
      were preserved in all arteries of non-pregnant and pregnant Restricted rats.
      Collagen and elastin content were unaltered in uterine arteries of Restricted
      females. Growth restricted females develop compensatory vascular changes during
      late pregnancy, such that region-specific vascular deficits observed in the non
      pregnant state did not persist in late pregnancy.

PMID- 22586218
TI  - Coronary wave intensity during the Valsalva manoeuvre in humans reflects altered
      intramural vessel compression responsible for extravascular resistance.
AB  - Our aim was to investigate the effect of altered cardiac-coronary interaction
      during the Valsalva manoeuvre (VM) on coronary wave intensity and the response of
      coronary microvascular resistance. In 13 patients, left ventricular (P(LV)) and
      aortic pressure were measured during catheterization, together with intracoronary
      pressure and blood flow velocity (U) via a dual-sensor guide wire advanced into
      an angiographically normal coronary artery. Signals were analysed for the
      following phases of VM: baseline (B1), onset of strain (S1), sustained strain
      (S2), onset of release (R1), maximal response during recovery (R2), and baseline
      after VM. The immediate effects of VM were most evident from diastolic P(LV)
      (LVDP), which increased from 11.0 +/- 2.3 to 36.4 +/- 2.7 mmHg between B1 and S1
      and fell from 28.3 +/- 3.4 to 8.3 +/- 1.9 mmHg between S2 and R1. Wave
      intensities and rate pressure product (RPP) were only minimally affected at these
      transient phases, but coronary wave energies decreased by about 50% and RPP by
      38% from S1 to S2, together with a 30% depression of LVdP/dt. All signals were
      restored to baseline values during the recovery. U did not vary significantly
      throughout the VM. Despite the depressed cardiac performance during VM strain,
      microvascular resistance, calculated with LVDP as backpressure, decreased by 31%
      from B1 to S2, whereas an increase via metabolically induced vasoconstriction was
      expected. Since coronary U remained essentially constant despite the marked
      reduction in oxygen consumption, microvascular vasoconstriction must have been
      compensated by a decrease in the contraction-mediated impediment on coronary
      blood flow, as confirmed by the reduced coronary wave energies.

PMID- 22586219
TI  - Theoretical study of L-type Ca(2+) current inactivation kinetics during action
      potential repolarization and early afterdepolarizations.
AB  - Sarcoplasmic reticulum (SR) Ca(2+) release mediates excitation-contraction
      coupling (ECC) in cardiac myocytes. It is triggered upon membrane depolarization
      by entry of Ca(2+) via L-type Ca(2+) channels (LTCCs), which undergo both voltage
      and Ca(2+)-dependent inactivation (VDI and CDI, respectively). We developed
      improved models of L-type Ca(2+) current and SR Ca(2+) release within the
      framework of the Shannon-Bers rabbit ventricular action potential (AP) model. The
      formulation of SR Ca(2+) release was modified to reproduce high ECC gain at
      negative membrane voltages. An existing LTCC model was extended to reflect more
      faithfully contributions of CDI and VDI to total inactivation. Ba(2+) current
      inactivation included an ion-dependent component (albeit small compared with
      CDI), in addition to pure VDI. Under physiological conditions (during an AP) LTCC
      inactivates predominantly via CDI, which is controlled mostly by SR Ca(2+)
      release during the initial AP phase, but by Ca(2+) through LTCCs for the
      remaining part. Simulations of decreased CDI or K(+) channel block predicted the
      occurrence of early and delayed after depolarizations. Our model accurately
      describes ECC and allows dissection of the relative contributions of different
      Ca(2+) sources to total CDI, and the relative roles of CDI and VDI, during normal
      and abnormal repolarization.

PMID- 22586220
TI  - Functional coupling of the metabotropic glutamate receptor, InsP3 receptor and L
      type Ca2+ channel in mouse CA1 pyramidal cells.
AB  - Activity-dependent regulation of calcium dynamics in neuronal cells can play
      significant roles in the modulation of many cellular processes such as
      intracellular signalling, neuronal activity and synaptic plasticity. Among many
      calcium influx pathways into neurons, the voltage-dependent calcium channel
      (VDCC) is the major source of calcium influx, but its modulation by synaptic
      activity has still been under debate. While the metabotropic glutamate receptor
      (mGluR) is supposed to modulate L-type VDCCs (L-VDCCs), its reported actions
      include both facilitation and suppression, probably reflecting the uncertainty of
      both the molecular targets of the mGluR agonists and the source of the recorded
      calcium signal in previous reports. In this study, using subtype-specific
      knockout mice, we have shown that mGluR5 induces facilitation of the
      depolarization-evoked calcium current. This facilitation was not accompanied by
      the change in single-channel properties of the VDCC itself; instead, it required
      the activation of calcium-induced calcium release (CICR) that was triggered by
      VDCC opening, suggesting that the opening of CICR-coupled cation channels was
      essential for the facilitation. This facilitation was blocked or reduced by the
      inhibitors of both L-VDCCs and InsP3 receptors (InsP3Rs). Furthermore, L-VDCCs
      and mGluR5 were shown to form a complex by coimmunoprecipitation, suggesting that
      the specific functional coupling between mGluR5, InsP3Rs and L-VDCCs played a
      pivotal role in the calcium-current facilitation. Finally, we showed that mGluR5
      enhanced VDCC-dependent long-term potentiation (LTP) of synaptic transmission.
      Our study has identified a novel mechanism of the interaction between the mGluR
      and calcium signalling, and suggested a contribution of mGluR5 to synaptic
      plasticity.

PMID- 22586221
TI  - Permeation, selectivity and gating in store-operated CRAC channels.
AB  - Store-operated Ca(2+) release-activated Ca(2+) (CRAC) channels are a widespread
      mechanism for generating cellular Ca(2+) signals and regulate many Ca(2+)
      dependent functions, including transcription, motility and proliferation. The
      opening of CRAC channels in response to depletion of intracellular Ca(2+) stores
      involves a cascade of cellular events that culminate in direct interactions
      between STIM1, the endoplasmic reticulum Ca(2+) sensor, and the channels composed
      of Orai proteins. Evidence gathered over the last two decades indicates that CRAC
      channels display a unique functional pore fingerprint characterized by exquisite
      Ca(2+) selectivity, low unitary conductance, and low permeability to large
      cations. Here, we review the key pore properties of CRAC channels and discuss
      recent progress in addressing the molecular foundations of these properties.
      Structure-function and cysteine-scanning studies have revealed the identity and
      organization of pore-lining residues, including those that form the selectivity
      filter, providing a structural framework for understanding CRAC channel pore
      properties. Recent studies in pore mutants that produce STIM1-independent
      constitutive channel activation indicate that exquisite Ca(2+) selectivity in
      CRAC channels is not hardwired into Orai proteins, but is instead manifested only
      following the binding of STIM1 to the intrinsically poorly Ca(2+)-selective Orai
      channels. These findings reveal new functional aspects of CRAC channels and
      suggest that the selectivity filter of the CRAC channel is a dynamic structure
      whose conformation and functional properties are powerfully regulated by the
      channel activation stimulus.

PMID- 22586222
TI  - Three-dimensional mechanisms of increased vulnerability to electric shocks in
      myocardial infarction: altered virtual electrode polarizations and conduction
      delay in the peri-infarct zone.
AB  - Defibrillation efficacy is decreased in infarcted hearts, but the mechanisms by
      which infarcted hearts are more vulnerable to electric shocks than healthy hearts
      remain poorly understood. The goal of this study was to provide insight into the
      3D mechanisms for the increased vulnerability to electric shocks in infarcted
      hearts. We hypothesized that changes in virtual electrode polarizations (VEPs)
      and propagation delay through the peri-infarct zone (PZ) were responsible. We
      developed a micro anatomically detailed rabbit ventricular model with chronic
      myocardial infarction from magnetic resonance imaging and enriched the model with
      data from optical mapping experiments. We further developed a control model
      without the infarct. The simulation protocol involved apical pacing followed by
      biphasic shocks. Simulation results from both models were compared.The upper
      limit of vulnerability(ULV) was 8 V cm(-1) in the infarction model and 4 V cm(-1)
      in the control model. VEPs were less pronounced in the infarction model,
      providing a larger excitable area for postshock propagation but smaller
      transmembrane potential gradients to initiate new wavefronts. Initial post-shock
      transmural activation occurred at a later time in the infarction model, and the
      PZ served to delay propagation in subsequent beats. The presence of the PZ was
      found to be responsible for the increased vulnerability.

PMID- 22586223
TI  - Regulation of blood flow distribution in skeletal muscle: role of erythrocyte
      released ATP.
AB  - The maintenance of adequate tissue O(2) levels in skeletal muscle is vital for
      normal physiology and requires a well regulated and appropriately distributed
      convective O(2) supply. Inherent in this fundamental physiological process is the
      requirement for a mechanism which both senses tissue O(2) need and locally
      adjusts flow to appropriately meet that need. Over the past several years we and
      others have suggested that, in skeletal muscle, O(2) carrying erythrocytes
      participate in the regulation of total blood flow and its distribution by
      releasing ATP. Importantly, the release of this vasoactive molecule must be both
      rapid and well controlled if it is to serve an important physiological role. Here
      we provide insights into three distinct regulated signalling pathways within the
      erythrocyte that are activated by exposure to reduced O(2) tension or in response
      to binding of agonists to the prostacyclin or beta-adrenergic receptors. Although
      much has been learned about the role of the erythrocyte in perfusion of skeletal
      muscle, much remains to be understood. However, what is clear is that the long
      established passive carrier of O(2) also contributes to the regulation of the
      distribution of microvascular perfusion in skeletal muscle by virtue of its
      capacity to release ATP.

PMID- 22586224
TI  - Reactive oxygen species contribute to the development of arrhythmogenic Ca2+
      waves during beta-adrenergic receptor stimulation in rabbit cardiomyocytes.
AB  - While beta-adrenergic receptor (beta-AR) stimulation leads to positive inotropic
      effects, it can also induce arrhythmogenic Ca2+ waves. beta-AR stimulation
      increases mitochondrial oxygen consumption and, thereby, the production of
      reactive oxygen species (ROS). We therefore investigated the role of ROS in the
      generation of Ca2+ waves during beta-AR stimulation in rabbit ventricular
      myocytes. Isoproterenol (ISO) increased Ca2+ transient amplitude during systole,
      sarcoplasmic reticulum (SR) Ca2+ load and the occurrence of Ca2+ waves during
      diastole. These effects, however, developed at different time points during ISO
      application.While SR Ca2+ release and load reached a maximum level after 3 min,
      Ca2+ waves occurred at the highest frequency only after 6 min of ISO
      application.Measurement of intra-SR-free Ca2+ concentration ([Ca2+]SR) showed an
      initial increase of SR Ca2+ load followed by a gradual decline over time during
      ISO application. This decline of [Ca2+]SR was not due to decreased SR Ca2+
      uptake, but instead was the result of increased SRCa2+ leak mainly in the form of
      Ca2+ waves. ISO application led to significant RyR phosphorylation at the protein
      kinase A (PKA)-specific site, which remained relatively stable throughout beta-AR
      activation.Moreover, beta-AR stimulation significantly increased ROS production
      after 4-6 min of ISO application. The ROS scavenger Tiron and the superoxide
      dismutase mimetic MnTBPA abolished the ISO-mediated ROS production. The
      mitochondria-specific antioxidant Mito-Tempo and an inhibitor of the electron
      transport chain, rotenone, also effectively prevented the ISO-mediated ROS
      production. Scavenging ROS during ISO application decreased the occurrence of
      Ca2+ waves and partially prevented augmentation of SRCa2+ leak, but did not
      affect the increase of Ca2+ transient amplitude. Treatment of myocytes with ISO
      for 15 min significantly reduced the free thiol content in RyRs. These data
      suggest that increased mitochondrial ROS production during beta-AR stimulation
      causes RyR oxidation. Together with RyR phosphorylation, oxidation of RyRs
      increases diastolic SR Ca2+ leak to a critical level leading to the generation of
      arrhythmogenic Ca2+ waves.

PMID- 22586227
TI  - Fukushima--one year later.

PMID- 22586225
TI  - The electroneutral Na+:HCO3- cotransporter NBCn1 is a major pHi regulator in
      murine duodenum.
AB  - Duodenocyte pHi control and HCO3 - secretion protects the proximal duodenum
      against damage by gastric acid. The molecular details of duodenocyte pH control
      are not well understood. A selective duodenal expression (within the upper GI
      tract) has been reported for the electroneutral Na+:HCO3 - cotransporter NBCn1
      (Slc4a7). We aimed to determine the role of NBCn1 and NBCe2 in duodenocyte
      intracellular pH regulation as well as basal and agonist-stimulated duodenal
      bicarbonate secretion (JHCO3 -), exploiting mouse models of genetic slc4a7 and
      slc4a5 disruption. Basal and forskolin (FSK)-stimulated JHCO3 - was measured by
      single-pass perfusion in the duodenum of slc4a7-/- and slc4a7+/+ as well as
      slc4a5-/- and slc4a5+/+ mice in vivo, and by pH-stat titration in isolated
      duodenal mucosa in vitro. Duodenocyte HCO3 - uptake rates were fluorometrically
      assessed after acidification of intact villi and of isolated duodenocytes. Slc4a7
      /- mice displayed significantly lower basal and FSK-stimulated duodenal HCO3 -
      secretion than slc4a7+/+ littermates in vivo. FSK-stimulated HCO3 - secretion was
      significantly reduced in slc4a7-/- isolated duodenal mucosa. Na+- and HCO3 -
      dependent base uptake rates were significantly decreased in slc4a7-/- compared
      with slc4a7+/+ villus duodenocytes when measured in intact villi. Carbonic
      anhydrase (CA)-mediated CO2 hydration played no apparent role as a HCO3 - supply
      mechanism for basal or FSK-stimulated secretion in the slc4a7+/+ duodenum, but
      was an important alternative HCO3 - supply mechanism in the slc4a7-/- duodenum.
      NBCe2 (Slc4a5) displayed markedly lower duodenal mRNA expression levels, and its
      disruption did not interfere with duodenal HCO3 - secretion. The electroneutral
      Na+:HCO3 - cotransporter NBCn1 (slc4a7) is a major duodenal HCO3 - importer that
      supplies HCO3 - during basal and FSK-stimulated HCO3 - secretion.

PMID- 22586231
TI  - How effective are non-drug, non-surgical treatments for primary dysmenorrhoea?

PMID- 22586230
TI  - A weak leg.

PMID- 22586226
TI  - Regulation of prefrontal excitatory neurotransmission by dopamine in the nucleus
      accumbens core.
AB  - Interactions between dopamine and glutamate signalling within the nucleus
      accumbens core are required for behavioural reinforcement and habit formation.
      Dopamine modulates excitatory glutamatergic signals from the prefrontal cortex,
      but the precise mechanism has not been identified. We combined optical and
      electrophysiology recordings in murine slice preparations from CB1 receptor-null
      mice and green fluorescent protein hemizygotic bacterial artificial chromosome
      transgenic mice to show how dopamine regulates glutamatergic synapses specific to
      the striatonigral and striatopallidal basal ganglia pathways. At low cortical
      frequencies, dopamine D1 receptors promote glutamate release to both D1 and D2
      receptor-expressing medium spiny neurons while D2 receptors specifically inhibit
      excitatory inputs to D2 receptor-expressing cells by decreasing exocytosis from
      cortical terminals with a low probability of release. At higher cortical
      stimulation frequencies, this dopaminergic modulation of presynaptic activity is
      occluded by adenosine and endocannabinoids. Glutamatergic inputs to both D1 and
      D2 receptor-bearing medium spiny neurons are inhibited by adenosine, released
      upon activation of NMDA and AMPA receptors and adenylyl cyclase in D1 receptor
      expressing cells. Excitatory inputs to D2 receptor-expressing cells are
      specifically inhibited by endocannabinoids, whose release is dependent on D2 and
      group 1 metabotropic glutamate receptors. The convergence of excitatory and
      inhibitory modulation of corticoaccumbal activity by dopamine, adenosine and
      endocannabinoids creates subsets of corticoaccumbal inputs, selectively and
      temporally reinforces strong cortical signals through the striatonigral pathway
      while inhibiting the weak, and may provide a mechanism whereby continued
      attention might be focused on behaviourally salient information.

PMID- 22586232
TI  - Tick bite and early Lyme borreliosis.

PMID- 22586233
TI  - Keeping patients safe while avoiding bias in randomised trials.

PMID- 22586234
TI  - Canada's first mental health strategy calls for major improvements to services.

PMID- 22586235
TI  - Dying remains a taboo subject for patients and GPs, finds survey.

PMID- 22586236
TI  - CCG funding could be based on population age, not deprivation, says Lansley.

PMID- 22586237
TI  - More than half of diabetes patients are not getting standard health checks.

PMID- 22586238
TI  - Reverse marsupialization technique of defibulation to restore vulvo-perineal
      elasticity: a case report and description of technique.
AB  - A 'reverse marsupialization' technique was used to restore vulval and perineal
      elasticity in order to improve the reproductive and sexual health of a woman with
      severely scarred vulva and perineum following infibulations.

PMID- 22586239
TI  - American Society for Gastrointestinal Endoscopy guidelines for appropriate use of
      colonoscopy: are they suitable for African patients?
AB  - This study investigates the appropriateness and diagnostic yield of colonoscopy
      referrals in an African setting using the American Society of Gastrointestinal
      Endoscopy guidelines: a prospective, descriptive, cross-sectional hospital-based
      study. A total of 311 patients were included in the study; 228 referrals (73.3%)
      were considered appropriate and clinically significant pathology was found in 157
      patients, giving an overall diagnostic yield of 50.5%. Diagnostic yield in those
      with appropriate referrals was 58.8% and 27.7% (P = 0.004) in those with
      inappropriate referrals. In our setting these guidelines are useful in improving
      diagnostic yield and reducing the rate of inappropriate referrals for
      colonoscopy. However, patients above the age of 50 presenting with lower
      gastrointestinal symptoms should undergo a colonoscopy even if the indication was
      inappropriate, especially in countries which are not implementing colorectal
      cancer screening programmes for average risk patients.

PMID- 22586240
TI  - Determination of uranium in seawater samples by liquid chromatography using
      mandelic acid as a complexing agent.
AB  - The determination of uranium at different stages of the recovery process as well
      as in seawater is important in its recovery study. A previous study developed a
      high-performance liquid chromatography (HPLC) method for uranium determination in
      seawater using alpha-hydroxy isobutyric acid as a chelating agent. However, this
      method causes turbidity in process samples containing high amounts of iron,
      resulting in the clogging of the HPLC column. In the present work, use of
      mandelic acid as a chelating agent for uranium has been explored. Elution
      conditions were optimized for the separation of iron [Fe(III)] and uranium
      [U(VI)] by studying the effect of an ion interaction reagent, the concentration
      of mandelic acid, and methanol content in the mobile phase. Different parameters
      were optimized to develop off- line pre-concentration of uranyl-mandelate on the
      reversed stationary phase. The method offers quantitative recovery of uranium and
      linearity in the U(VI) concentration range of 0.5 ppb to 500 ppb and can be used
      for the determination of U(VI) in process samples with Fe/U amount ratios up to
      3,000. The method has been successfully used for the determination of U(VI) in
      seawater samples and process samples. The developed methodology was validated by
      comparing the results with those of isotope dilution-thermal ionization mass
      spectrometry.

PMID- 22586241
TI  - Determination of microcystin-LR in drinking water using UPLC tandem mass
      spectrometry-matrix effects and measurement.
AB  - A simple detection method using ultra-performance liquid chromatography
      electrospray ionisation tandem mass spectrometry (UPLC-ESI-MS-MS) coupled with
      the sample dilution method for determining trace microcystin-LR (MC-LR) in
      drinking water is presented. The limit of detection (LOD) was 0.04 ug/L and the
      limit of quantitation (LOQ) was 0.1 ug/L. Water matrix effects of ionic strength,
      dissolved organic carbon (DOC) and pH were examined. The results indicate that
      signal detection intensity for MC-LR was significantly suppressed as the ionic
      strength increased from ultrapure water condition, whereas it increased slightly
      with solution pH and DOC at low concentrations. However, addition of methanol
      (MeOH) into the sample was able to counter the signal suppression effects. In
      this study, dilution of the tap water sample by adding 4% MeOH (v/v) was observed
      to be adequate to compensate for the signal suppression. The recoveries of the
      samples fortified with MC-LR (0.2, 1, and 10 ug/L) for three different tap water
      samples ranged from 84.4% to 112.9%.

PMID- 22586242
TI  - Determination of trace benzene derivatives in aqueous samples by ultrasonic
      enhanced hollow fiber liquid-phase microextraction prior to gas chromatography.
AB  - A new method was developed for the determination of trace compounds in water
      samples using ultrasonic-enhanced hollow fiber liquid-phase microextraction (U-HF
      LPME). The ultrasonic radiation, which produces mechanical vibration and
      ultrasonic cavitation, could be used for accelerating the diffusion mass transfer
      process. Thus, ultrasonic was introduced into the HF-LPME procedure to enhance
      the mass-transfer rate during the aqueous and extraction solvent phases.
      Experimental parameters such as the extraction solvent, the extraction time, the
      ultrasonic frequency and power, the extractant volume, and ionic strength of the
      sample were assessed and optimized. Under optimal conditions, HF-LPME was
      achieved within 10 min. The high enrichment factor in the range of 120-666 and a
      good relative recovery in the range of 97-103% were evaluated with the relative
      standard deviations (RSDs, n = 5) of 0.3-7.0%. The limit of detection was in the
      range of 0.8-3.0 ug/L. The method was applied to the analysis of groundwater,
      lake water, and seawater. The results showed that the method can determine trace
      benzene derivatives in real samples with RSD values of 1.1-4.2%. The results
      demonstrated that U-HF- LPME is a rapid, accurate, and effective sample
      preparation method, and could be successfully applied for the determination of
      trace compounds in analytical chemistry.

PMID- 22586243
TI  - Enrichment and determination of trace estradiol in environmental water samples by
      hollow-fiber liquid-phase microextraction prior to HPLC.
AB  - This paper presents a novel and simple cleanup procedure based on hollow fiber
      liquid-phase microextraction (HF-LPME) for the determination of trace estradiol
      in environmental. Estradiol was extracted from a 140-mL water sample (the donor
      phase) into the pores of the hollow fiber wall organic solvent, then into the
      organic solvent (the acceptor phase) in the lumen of the hollow fiber.
      Afterwards, the hollow fiber was eluted with methanol to capture estradiol from
      the acceptor phase. Different experimental parameters, including the organic
      phase type and its volume, compositions of the donor phases, ionic strength,
      stirring rate, temperature, and the extraction times were controlled and
      optimized based on the response of the HPLC instrument. Under the optimized
      experimental conditions, the proposed method was found to be linear in the
      concentration of 1-1000 ng/mL for estradiol, and the limit of detection was 0.1
      ng/mL. Furthermore, the method provided a good enrichment factor of 300, and
      repeatability (relative standard deviation = 5.5). Finally, the proposed method
      was applied for the analysis of real environmental samples.

PMID- 22586244
TI  - Bamboo charcoal as adsorbent for SPE coupled with monolithic column-HPLC for
      rapid determination of 16 polycyclic aromatic hydrocarbons in water samples.
AB  - The coupling of solid-phase extraction (SPE) using bamboo charcoal (BC) as an
      adsorbent with a monolithic column-high performance liquid chromatography (MC
      HPLC) method was developed for the high-efficiency enrichment and rapid
      determination of 16 polycyclic aromatic hydrocarbons (PAHs) in water. Key
      influence factors, such as the type and the volume of the elution solvent, and
      the flow rate and the volume of the sample loading, were optimized to obtain a
      high SPE recovery and extraction efficiency. BC as an SPE adsorbent presented a
      high extraction efficiency due to its large specific surface area and high
      adsorption capacity; MC as an HPLC column accelerated the separation within 8 min
      because of its high porosity, fast mass transfer, and low-pressure resistance.
      The calibration curves for the PAHs extracted were linear in the range of 0.2-15
      ug/L, with the correlation coefficients (r(2)) between 0.9970-0.9999. This method
      attained good precisions (relative standard deviation, RSD) from 3.5 to 10.9% for
      the standard PAHs I aqueous solutions at 5 ug/L; the method recoveries ranged in
      52.6-121.6% for real spiked river water samples with 0.4 and 4 ug/L. The limits
      of detection (LODs, S/N = 3) of the method were determined from 11 and 87 ng/L.
      The developed method was demonstrated to be applicable for the rapid and
      sensitive determination of 16 PAHs in real environmental water samples.

PMID- 22586245
TI  - Determination of triazine herbicides in environmental samples by dispersive
      liquid-liquid microextraction coupled with high performance liquid
      chromatography.
AB  - A simple, rapid, efficient, and environmentally friendly method for the
      determination of five triazine herbicides in water and soil samples was developed
      by using dispersive liquid-liquid microextraction (DLLME), coupled with high
      performance liquid chromatography-diode array detection (HPLC-DAD). The water
      samples were directly used for DLLME extraction. For soil samples, the target
      analytes were first extracted by water-methanol (99:1, v/v). In the DLLME
      extraction method, chloroform was used as an extraction solvent, and acetonitrile
      as a dispersive solvent. Under the optimum conditions, the enrichment factors of
      DLLME were in the range between 183-221. The linearity of the method was obtained
      in the range of 0.5-200 ng/mL for the water sample analysis, and 1-200 ng/g for
      the soil samples, respectively. The correlation coefficients ranged from 0.9968
      to 0.9999. The limits of detection were 0.05-0.1 ng/mL for the water samples, and
      0.1-0.2 ng/g for the soil samples. The proposed method has been successfully
      applied to the analysis of target triazine herbicides (simazin, atrazine,
      prometon, ametryn, and prometryn) in water and soil samples with satisfactory
      results.

PMID- 22586246
TI  - Determination of polycyclic aromatic hydrocarbons in coastal sediments from the
      Porto region (Portugal) by microwave-assisted extraction, followed by SPME and GC
      MS.
AB  - A simple low-cost, analytical method based on microwave-assisted extraction of
      sediments, followed by solid phase micro-extraction and gas chromatography mass
      spectrometry, was developed and validated for the quantification of sixteen
      polycyclic aromatic hydrocarbons (PAHs) in marine and estuarine sediment samples.
      The PAHs were those included in the United States Environmental Protection Agency
      (US EPA) priority list. Method detection limits were between 0.07 and 0.76 ug/kg
      dry weight (dw), which makes the current method suitable for environmental
      analysis. Sediments screened for PAHs from the Douro River estuary and the Porto
      seacoast exhibit total concentrations that ranged from 58.98 to 156.45 ug/kg dw,
      and from 51.98 to 54.79 ug/kg dw, respectively. The presence of almost all human
      carcinogenic PAHs in the analyzed areas indicate that these sediments can be
      considered polluted, suggesting that future monitoring programs together with an
      effective coastal management program must be implemented to guarantee the safe
      usage of the current areas for fishing and bathing.

PMID- 22586247
TI  - Dispersive solid-phase extraction cleanup combined with accelerated solvent
      extraction for the determination of carbamate pesticide residues in Radix
      Glycyrrhizae samples by UPLC-MS-MS.
AB  - Dispersive solid-phase extraction (DSPE) cleanup combined with accelerated
      solvent extraction (ASE) is described here as a new approach for the extraction
      of carbamate pesticides in Radix Glycyrrhizae samples prior to UPLC-MS-MS. In the
      DSPE-ASE method, 15 carbamate pesticides were extracted from Radix Glycyrrhizae
      samples with acetonitrile by the ASE method at 60  degrees C with a 5 min heating
      time and two static cycles. Cleanup of a 1 mL aliquot of the extract by the DSPE
      method used 20 mg PSA (primary secondary amine), 50 mg Al(2)O(3)-N, and 20 mg GCB
      (graphitized carbon black) (as cleanup sorbents) under the determined optimum
      conditions. The linearity of the method was in the range of 10 to 200 ng/mL with
      correlation coefficients (r(2)) of more than 0.996. The limits of detection were
      approximately 0.2 to 5.0 ug/kg. The method was successfully used for the analysis
      of target pesticides in Radix Glycyrrhizae samples. The recoveries of the
      carbamate pesticides at the spiking levels of 50, 100, and 200 ug/kg ranged from
      79.7% to 99.3% with relative standard deviations lower than 10%. This multi
      residue analytical method allows for a rapid, efficient, sensitive and reliable
      determination of target pesticides in Radix Glycyrrhizae and other medicinal
      herbs.

PMID- 22586248
TI  - Performance and matrix effect observed in QuEChERS extraction and tandem mass
      spectrometry analyses of pesticide residues in different target crops.
AB  - The method performance and matrix effect related to quantitative determination of
      pesticide residues was assessed after QuEChERS extraction and LC-MS-MS analysis.
      Dicloran, phosmet and phosmet-oxon, pirimiphos-methyl, and BNOA were analyzed in
      peach, apple, melon, cereals, tomato, and strawberry. The matrix effects, as well
      as recovery and process efficiencies, were determined for a fungicide, two
      insecticides, and a plant growth regulator. Crop samples were spiked either pre-
      or post-extraction, then the peak area was compared with the peak area in neat
      solvent. The mean recovery ranged from 73% to 98%, and repeatability (as RSD) was
      between 3% and 16%, depending on the compound and spiking level. The matrix
      effect occurred as ionic suppression and was found in the range of 5% to 22%
      depending on the compound. Recovery efficiencies were good and substantially
      comparable, being in the range of 93-96%. Although the suppression observed still
      appears to be acceptable considering the overall process efficiency, it seems
      evident that the matrix effect is important when a reliable quantitative method
      must be applied.

PMID- 22586249
TI  - Determination of pesticides in fruit and fruit juices by chromatographic methods.
      An overview.
AB  - In order to combat a variety of pests, pesticides are widely used in fruits.
      Several extraction procedures (liquid extraction, single drop microextraction,
      microwave-assisted extraction, pressurized liquid extraction, supercritical fluid
      extraction, solid-phase extraction, solid-phase microextraction, matrix solid
      phase dispersion, and stir bar sorptive extraction) have been reported to
      determine pesticide residues in fruits and fruit juices. The significant change
      in recent years is the introduction of the Quick, Easy, Cheap, Effective, Rugged,
      and Safe (QuEChERS) methods in these matrices analysis. A combination of
      techniques reported the use of new extraction methods and chromatography to
      provide better quantitative recoveries at low levels. The use of mass
      spectrometric detectors in combination with liquid and gas chromatography has
      played a vital role to solve many problems related to food safety. The main
      attention in this review is on the achievements that have been possible because
      of the progress in extraction methods and the latest advances and novelties in
      mass spectrometry, and how these progresses have influenced the best control of
      food, allowing for an increase in the food safety and quality standards.

PMID- 22586250
TI  - An evaluation of two calibration procedures using thermal desorption-gas
      chromatography in the analysis of odorous volatile compounds.
AB  - In this study, the relative performance of gas chromatography (GC) was
      investigated with respect to the differences in two types of calibration
      approaches with a thermal desorption (TD) method: the fixed standard
      concentration approach (FSC: the comparison of different sample volumes for a
      given standard) was compared with the fixed standard volume approach (FSV: the
      comparison of different concentration standards at a fixed loading volume).
      Gaseous working standards of seven odorants, including methyl ethyl ketone (MEK),
      butyl acetate, methyl isobutyl ketone, isobutyl alcohol, toluene, xylene, and a
      reference component, benzene, were prepared at four concentration levels (10-100
      ppb). They were then analyzed by controlling the TD-loading volumes at six levels
      (40-1200 mL). The results derived by these contrasting calibration approaches
      showed moderate changes in the GC sensitivity, either with an increasing
      concentration (i.e., FSC), or with an increasing sample loading volume (i.e.,
      FSV). Despite an eccentric trend of MEK, the TD-based analysis was fairly
      predictable and can be recommended for the analysis of the selected odorants.

PMID- 22586251
TI  - Enantiomeric resolution of five chiral pesticides on a Chiralpak IB-H column by
      SFC.
AB  - The enantiomeric separations of five chiral pesticides, diclofopmethyl, 1;
      benalaxy, 2; acetofenate, 3; myclobutanil, 4; and difenoconazole, 5, were
      conducted on a Chiralpak IB-H column by a packed-column supercritical fluid
      chromatography (p-SFC). All compounds, except difenoconazole and myclobutanil,
      were well resolved within 10 min. As the mobile phase polarity decreased through
      changing the percentage and the type of alcohol modifiers in the supercritical
      carbon dioxide (CO(2)), the retention time, the separation factors, and the
      resolution increased. However, based on the retention time and the resolution,
      the optimized separations were obtained with the mobile phase containing 10% 2
      propanol for diclofop-methyl 1; benalaxy, 2; myclobutanil, 4; difenoconazole, 5;
      and containing 3% 2-propanol for acetofenate, 3. The optimized separation
      temperature was at 35 degrees C under the supercritical fluid condition. The pi
      pi interactions and the hydrogen bonding interactions between Chiralpak IB-H CSP
      and the analytes might be the main chiral discriminations on enantioseparation of
      these five pesticides.

PMID- 22586252
TI  - MBSR vs aerobic exercise in social anxiety: fMRI of emotion regulation of
      negative self-beliefs.
AB  - Mindfulness-based stress reduction (MBSR) is thought to reduce emotional
      reactivity and enhance emotion regulation in patients with social anxiety
      disorder (SAD). The goal of this study was to examine the neural correlates of
      deploying attention to regulate responses to negative self-beliefs using
      functional magnetic resonance imaging. Participants were 56 patients with
      generalized SAD in a randomized controlled trial who were assigned to MBSR or a
      comparison aerobic exercise (AE) stress reduction program. Compared to AE, MBSR
      yielded greater (i) reductions in negative emotion when implementing regulation
      and (ii) increases in attention-related parietal cortical regions. Meditation
      practice was associated with decreases in negative emotion and social anxiety
      symptom severity, and increases in attention-related parietal cortex neural
      responses when implementing attention regulation of negative self-beliefs.
      Changes in attention regulation during MBSR may be an important psychological
      factor that helps to explain how mindfulness meditation training benefits
      patients with anxiety disorders.

PMID- 22586254
TI  - Reorganisation at Global Fund sparks $1.6bn in new donations.

PMID- 22586253
TI  - Arterolane maleate plus piperaquine phosphate for treatment of uncomplicated
      Plasmodium falciparum malaria: a comparative, multicenter, randomized clinical
      trial.
AB  - BACKGROUND: Artemisinin-based combination therapy is the first-line treatment for
      uncomplicated falciparum malaria. This study assessed the antimalarial efficacy
      and safety of a combination of 150 mg of arterolane maleate and 750 mg of
      piperaquine phosphate (AM-PQP) in comparison to Coartem (artemether and
      lumefantrine) in patients with acute uncomplicated P. falciparum malaria.
      METHODS: In this open-label, randomized, multicentric, parallel group clinical
      trial, 240 patients were randomized to receive AM-PQP (160 patients) or Coartem
      (80 patients). Patients with P. falciparum monoinfection and initial parasite
      densities ranging from 1000 to 100 000 asexual parasites/uL of blood were
      followed for 28 days. Polymerase chain reaction-corrected adequate clinical and
      parasitologic response on day 28, parasite clearance time, and fever clearance
      time were evaluated. RESULTS: A total of 151 (94.4%) of 160 patients in the AM
      PQP group completed the trial, while 77 (96.3%) of 80 patients in the Coartem
      group completed the trial. No treatment failure was noted in the AM-PQP group,
      while one patient receiving Coartem failed treatment on day 28. There was no
      difference in the median parasite clearance time (30 hours in both groups) or
      median fever clearance time (24 hours in both groups) after administration of the
      2 study treatments. CONCLUSIONS: The available data support the evaluation of a
      drug combination in a larger population as a fixed-dose combination. Clinical
      Trials Registration. CTRI/2007/091/000031.

PMID- 22586255
TI  - Old authoritarian patterns of doctors' behaviour are still alive and well in
      California, study shows.

PMID- 22586256
TI  - More Americans find healthcare unattainable, shows study.

PMID- 22586257
TI  - Hospitals in Wales need to reconfigure to improve patient outcomes, says report.

PMID- 22586258
TI  - Cheap alcohol is to be outlawed in Scotland.

PMID- 22586259
TI  - Pulmonary venous anatomy imaging with low-dose, prospectively ECG-triggered, high
      pitch 128-slice dual-source computed tomography.
AB  - BACKGROUND: The efforts to reduce radiation from cardiac computed tomography (CT)
      are essential. Using a prospectively triggered, high-pitch dual-source CT
      protocol, we aim to determine the radiation dose and image quality in patients
      undergoing pulmonary vein (PV) imaging. METHODS AND RESULTS: In 94 patients (61+/
      9 years; 71% male) who underwent 128-slice dual-source CT (pitch 3.4), radiation
      dose and image quality were assessed and compared between 69 patients with sinus
      rhythm and 25 patients with atrial fibrillation. Radiation dose was compared in a
      subset of 19 patients with prior retrospective or prospectively triggered CT PV
      scans without high pitch. In a subset of 18 patients with prior magnetic
      resonance imaging for PV assessment, PV anatomy and scan duration were compared
      with high-pitch CT. Using the high-pitch protocol, total effective radiation dose
      was 1.4 (1.3, 1.9) mSv, with no difference between sinus rhythm and atrial
      fibrillation (1.4 versus 1.5 mSv; P=0.22). No high-pitch CT scans were
      nondiagnostic or had poor image quality. Radiation dose was reduced with high
      pitch (1.6 mSv) compared with standard protocols (19.3 mSv; P<0.0001). This
      radiation dose reduction was seen with sinus rhythm (1.5 versus 16.7 mSv;
      P<0.0001) but was more profound with atrial fibrillation (1.9 versus 27.7 mSv;
      P=0.039). There was excellent agreement of PV anatomy (kappa 0.84; P<0.0001) and
      a shorter CT scan duration (6 minutes) compared with magnetic resonance imaging
      (41 minutes; P<0.0001). CONCLUSIONS: Using a high-pitch dual-source CT protocol,
      PV imaging can be performed with minimal radiation dose, short scan acquisition,
      and excellent image quality in patients with sinus rhythm or atrial fibrillation.
      This protocol highlights the success of new cardiac CT technology to minimize
      radiation exposure, giving clinicians a new low-dose imaging alternative to
      assess PV anatomy.

PMID- 22586260
TI  - Neural control of ventricular rate in ambulatory dogs with pacing-induced
      sustained atrial fibrillation.
AB  - BACKGROUND: We hypothesize that inferior vena cava-inferior atrial ganglionated
      plexus nerve activity (IVC-IAGPNA) is responsible for ventricular rate (VR)
      control during atrial fibrillation (AF) in ambulatory dogs. METHODS AND RESULTS:
      We recorded bilateral cervical vagal nerve activity (VNA) and IVC-IAGPNA during
      baseline sinus rhythm and during pacing-induced sustained AF in 6 ambulatory
      dogs. Integrated nerve activities and average VR were measured every 10 seconds
      over 24 hours. Left VNA was associated with VR reduction during AF in 5 dogs
      (from 211 bpm [95% CI, 186-233] to 178 bpm [95% CI, 145-210]; P<0.001) and right
      VNA in 1 dog (from 208 bpm [95% CI, 197-223] to 181 bpm [95% CI, 163-200];
      P<0.01). There were good correlations between IVC-IAGPNA and left VNA in the
      former 5 dogs and between IVC-IAGPNA and right VNA in the last dog. IVC-IAGPNA
      was associated with VR reduction in all dogs studied. Right VNA was associated
      with baseline sinus rate reduction from 105 bpm (95% CI, 95-116) to 77 bpm (95%
      CI, 64-91; P<0.01) in 4 dogs, whereas left VNA was associated with sinus rate
      reduction from 111 bpm (95% CI, 90-1250) to 81 bpm (95% CI, 67-103; P<0.01) in 2
      dogs. CONCLUSIONS: IVC-IAGPNA is invariably associated with VR reduction during
      AF. In comparison, right or left VNA was associated with VR reduction only when
      it coactivates with the IVC-IAGPNA. The vagal nerve that controls VR during AF
      may be different from that which controls sinus rhythm.

PMID- 22586261
TI  - Analysis of caregiver perceptions of "hallucinations" in people with dementia in
      institutional settings.
AB  - This study investigated the meanings and etiologies of hallucinations in persons
      with dementia. Participants were 74 nursing home residents aged >= 65 diagnosed
      with dementia. Most of the reported visual and auditory hallucinations involved
      talking to persons who are not present, a phenomenon described as either a visual
      or auditory hallucination, or both. All participants who were reported to
      experience a hallucination had poor vision. Current results suggest that
      hallucination was a term staff caregivers used for the phenomena they could not
      easily explain, demonstrating their lack of understanding of the resident and/or
      the phenomena they termed hallucination. The classification of hallucinations
      into subtypes may not be meaningful, and most visual and auditory hallucinations
      were not associated with negative affect. Some hallucinations occurred out of
      boredom, which exacerbated the sensory deprivation experienced by these persons,
      thereby increasing the likelihood of hallucinations.

PMID- 22586262
TI  - Loss of synaptophysin immunoexpression in primary progressive aphasia.
AB  - Primary progressive aphasia (PPA) is characterized by progressive loss of
      language, unassociated with generalized cognitive loss and with no uniform
      pathological abnormality. To address whether the issue of PPA is associated with
      synaptic loss, we compared immunoreactivity in Broca's area with that in the
      adjacent gyrus from a case of progressive, nonfluent PPA using antibodies against
      synaptophysin. Using semiautomated methods, we assessed serial 0.10 mm(2)
      diameter areas from the cortical surface to the white matter in both the case and
      the control. In PPA, synaptophysin immunoreactivity was significantly less in
      Broca's area than in the adjacent area (optical densities of 0.16 and 0.24). The
      reduced synaptophysin immunoreactivity was significantly greater in the upper
      cortex than in the regions of cortex adjacent to the white matter (mean optical
      densities of 0.14 and 0.18). These data suggest that synaptic loss may be a
      factor underlying the language deficits in PPA.

PMID- 22586263
TI  - Sir3 and epigenetic inheritance of silent chromatin in Saccharomyces cerevisiae.
AB  - Epigenetic mechanisms maintain the specific characteristics of differentiated
      cells by ensuring the inheritance of gene expression patterns through DNA
      replication and mitosis. We examined the mechanism of epigenetic inheritance of
      Sir protein-dependent transcriptional silencing in Saccharomyces cerevisiae by
      examining gene expression and molecular markers of silencing at the silent mating
      type loci under conditions of limiting Sir3 protein. We observed that silencing
      at HMR, as previously reported for HML, is epigenetically inherited. This
      inheritance is accompanied by an increased ability of previously silenced cells
      to retain or recruit limiting Sir3 protein to cis-acting silencer sequences. We
      also observed that the low H4-K16 histone acetylation and H3-K79 methylation
      associated with a silenced HMR locus persist in recently derepressed cells for
      several generations at levels of Sir3 insufficient to maintain these marks in
      long-term-derepressed cells. The unique ability of previously silenced cells to
      retain Sir3 protein, maintain silencing-specific histone modifications, and
      repress HMR transcription at levels of Sir3 insufficient to mediate these effects
      in long-term-derepressed cells suggests that a cis-acting, chromatin-based
      mechanism drives epigenetic inheritance at this locus.

PMID- 22586264
TI  - SIRT1 negatively regulates the activities, functions, and protein levels of hMOF
      and TIP60.
AB  - SIRT1 is a NAD(+)-dependent histone H4K16 deacetylase that controls several
      different normal physiologic and disease processes. Like most histone
      deacetylases, SIRT1 also deacetylates nonhistone proteins. Here, we show that two
      members of the MYST (MOZ, Ybf2/Sas3, Sas2, and TIP60) acetyltransferase family,
      hMOF and TIP60, are SIRT1 substrates. SIRT1 deacetylation of the enzymatic
      domains of hMOF and TIP60 inhibits their acetyltransferase activity and promotes
      ubiquitination-dependent degradation of these proteins. Importantly, immediately
      following DNA damage, the binding of SIRT1 to hMOF and TIP60 is transiently
      interrupted, with corresponding hMOF/TIP60 hyperacetylation. Lysine-to-arginine
      mutations in SIRT1-targeted lysines on hMOF and TIP60 repress DNA double-strand
      break repair and inhibit the ability of hMOF/TIP60 to induce apoptosis in
      response to DNA double-strand break. Together, these findings uncover novel
      pathways in which SIRT1 dynamically interacts with and regulates hMOF and TIP60
      through deacetylation and provide additional mechanistic insights by which SIRT1
      regulates DNA damage response.

PMID- 22586265
TI  - Regulatory effects of programmed cell death 4 (PDCD4) protein in interferon (IFN)
      stimulated gene expression and generation of type I IFN responses.
AB  - The precise mechanisms by which the activation of interferon (IFN) receptors
      (IFNRs) ultimately controls mRNA translation of specific target genes to induce
      IFN-dependent biological responses remain ill defined. We provide evidence that
      IFN-alpha induces phosphorylation of programmed cell death 4 (PDCD4) protein on
      Ser67. This IFN-alpha-dependent phosphorylation is mediated by either the p70 S6
      kinase (S6K) or the p90 ribosomal protein S6K (RSK) in a cell-type-specific
      manner. IFN-dependent phosphorylation of PDCD4 results in downregulation of PDCD4
      protein levels as the phosphorylated form of PDCD4 interacts with the ubiquitin
      ligase beta-TRCP (beta-transducin repeat-containing protein) and undergoes
      degradation. This process facilitates IFN-induced eukaryotic translation
      initiation factor 4A (eIF4A) activity and binding to translation initiation
      factor eIF4G to promote mRNA translation. Our data establish that PDCD4
      degradation ultimately facilitates expression of several ISG protein products
      that play important roles in the generation of IFN responses, including IFN
      stimulated gene 15 (ISG15), p21(WAF1/CIP1), and Schlafen 5 (SLFN5). Moreover,
      engagement of the RSK/PDCD4 pathway by the type I IFNR is required for the
      suppressive effects of IFN-alpha on normal CD34(+) hematopoietic precursors and
      for antileukemic effects in vitro. Altogether, these findings provide evidence
      for a unique function of PDCD4 in the type I IFN system and indicate a key
      regulatory role for this protein in mRNA translation of ISGs and control of IFN
      responses.

PMID- 22586266
TI  - Blockade of the activin receptor IIb activates functional brown adipogenesis and
      thermogenesis by inducing mitochondrial oxidative metabolism.
AB  - Brown adipose tissue (BAT) is a key tissue for energy expenditure via fat and
      glucose oxidation for thermogenesis. In this study, we demonstrate that the
      myostatin/activin receptor IIB (ActRIIB) pathway, which serves as an important
      negative regulator of muscle growth, is also a negative regulator of brown
      adipocyte differentiation. In parallel to the anticipated hypertrophy of skeletal
      muscle, the pharmacological inhibition of ActRIIB in mice, using a neutralizing
      antibody, increases the amount of BAT without directly affecting white adipose
      tissue. Mechanistically, inhibition of ActRIIB inhibits Smad3 signaling and
      activates the expression of myoglobin and PGC-1 coregulators in brown adipocytes.
      Consequently, ActRIIB blockade in brown adipose tissue enhances mitochondrial
      function and uncoupled respiration, translating into beneficial functional
      consequences, including enhanced cold tolerance and increased energy expenditure.
      Importantly, ActRIIB inhibition enhanced energy expenditure only at ambient
      temperature or in the cold and not at thermoneutrality, where nonshivering
      thermogenesis is minimal, strongly suggesting that brown fat activation plays a
      prominent role in the metabolic actions of ActRIIB inhibition.

PMID- 22586267
TI  - The AMPK beta2 subunit is required for energy homeostasis during metabolic
      stress.
AB  - AMP activated protein kinase (AMPK) plays a key role in the regulatory network
      responsible for maintaining systemic energy homeostasis during exercise or
      nutrient deprivation. To understand the function of the regulatory beta2 subunit
      of AMPK in systemic energy metabolism, we characterized beta2 subunit-deficient
      mice. Using these mutant mice, we demonstrated that the beta2 subunit plays an
      important role in regulating glucose, glycogen, and lipid metabolism during
      metabolic stress. The beta2 mutant animals failed to maintain euglycemia and
      muscle ATP levels during fasting. In addition, beta2-deficient animals showed
      classic symptoms of metabolic syndrome, including hyperglycemia, glucose
      intolerance, and insulin resistance when maintained on a high-fat diet (HFD), and
      were unable to maintain muscle ATP levels during exercise. Cell surface
      associated glucose transporter levels were reduced in skeletal muscle from beta2
      mutant animals on an HFD. In addition, they displayed poor exercise performance
      and impaired muscle glycogen metabolism. These mutant mice had decreased
      activation of AMPK and deficits in PGC1alpha-mediated transcription in skeletal
      muscle. Our results highlight specific roles of AMPK complexes containing the
      beta2 subunit and suggest the potential utility of AMPK isoform-specific
      pharmacological modulators for treatment of metabolic, cardiac, and neurological
      disorders.

PMID- 22586268
TI  - Sphingolipids regulate the yeast high-osmolarity glycerol response pathway.
AB  - The yeast high-osmolarity glycerol response (HOG) mitogen-activated protein (MAP)
      kinase pathway is activated in response to hyperosmotic stress via two
      independent osmosensing branches, the Sln1 branch and the Sho1 branch. While the
      mechanism by which the osmosensing machinery activates the downstream MAP kinase
      cascade has been well studied, the mechanism by which the machinery senses and
      responds to hyperosmotic stress remains to be clarified. Here we report that
      inhibition of the de novo sphingolipid synthesis pathway results in activation of
      the HOG pathway via both branches. Inhibition of ergosterol biosynthesis also
      induces activation of the HOG pathway. Sphingolipids and sterols are known to be
      tightly packed together in cell membranes to form partitioned domains called
      rafts. Raft-enriched detergent-resistant membranes (DRMs) contain both Sln1 and
      Sho1, and sphingolipid depletion and hyperosmotic stress have similar effects on
      the osmosensing machinery of the HOG pathway: dissociation of an Sln1-containing
      protein complex and elevated association of Sho1 with DRMs. These observations
      reveal the sphingolipid-mediated regulation of the osmosensing machinery of the
      HOG pathway.

PMID- 22586270
TI  - Identification of estrogen receptor beta as a SUMO-1 target reveals a novel
      phosphorylated sumoylation motif and regulation by glycogen synthase kinase
      3beta.
AB  - SUMO conjugation has emerged as a dynamic process in regulating protein function.
      Here we identify estrogen receptor beta (ERbeta) to be a new target of SUMO-1.
      ERbeta SUMO-1 modification occurs on a unique nonconsensus sumoylation motif
      which becomes fully competent upon phosphorylation of its contained serine
      residue, which provides the essential negative charge for sumoylation. This
      process is further regulated by phosphorylation of additional adjacent serine
      residues by glycogen synthase kinase 3beta (GSK3beta), which maximizes ERbeta
      sumoylation in response to hormone. SUMO-1 attachment prevents ERbeta degradation
      by competing with ubiquitin at the same acceptor site and dictates ERbeta
      transcriptional inhibition by altering estrogen-responsive target promoter
      occupancy and gene expression in breast cancer cells. These findings uncovered a
      novel phosphorylated sumoylation motif (pSuM), which consists of the sequence
      psiKXS (where psi represents a large hydrophobic residue) and which is connected
      to a GSK3-activated extension that functions as a SUMO enhancer. This extended
      pSuM offers a valuable signature to predict SUMO substrates under protein kinase
      regulation.

PMID- 22586269
TI  - The SUMO pathway promotes basic helix-loop-helix proneural factor activity via a
      direct effect on the Zn finger protein senseless.
AB  - During development, proneural transcription factors of the basic helix-loop-helix
      (bHLH) family are required to commit cells to a neural fate. In Drosophila
      neurogenesis, a key mechanism promoting sense organ precursor (SOP) fate is the
      synergy between proneural factors and their coactivator Senseless in
      transcriptional activation of target genes. Here we present evidence that
      posttranslational modification by SUMO enhances this synergy via an effect on
      Senseless protein. We show that Senseless is a direct target for SUMO
      modification and that mutagenesis of a predicted SUMOylation motif in Senseless
      reduces Senseless/proneural synergy both in vivo and in cell culture. We propose
      that SUMOylation of Senseless via lysine 509 promotes its synergy with proneural
      proteins during transcriptional activation and hence regulates an important step
      in neurogenesis leading to the formation and maturation of the SOPs.

PMID- 22586271
TI  - Acyl coenzyme A thioesterase Them5/Acot15 is involved in cardiolipin remodeling
      and fatty liver development.
AB  - Acyl coenzyme A (acyl-CoA) thioesterases hydrolyze thioester bonds in acyl-CoA
      metabolites. The majority of mammalian thioesterases are alpha/beta-hydrolases
      and have been studied extensively. A second class of Hotdog-fold enzymes has been
      less well described. Here, we present a structural and functional analysis of a
      new mammalian mitochondrial thioesterase, Them5. Them5 and its paralog, Them4,
      adopt the classical Hotdog-fold structure and form homodimers in crystals. In
      vitro, Them5 shows strong thioesterase activity with long-chain acyl-CoAs. Loss
      of Them5 specifically alters the remodeling process of the mitochondrial
      phospholipid cardiolipin. Them5(-/-) mice show deregulation of lipid metabolism
      and the development of fatty liver, exacerbated by a high-fat diet. Consequently,
      mitochondrial morphology is affected, and functions such as respiration and beta
      oxidation are impaired. The novel mitochondrial acyl-CoA thioesterase Them5 has a
      critical and specific role in the cardiolipin remodeling process, connecting it
      to the development of fatty liver and related conditions.

PMID- 22586273
TI  - Dynamic reconfiguration of long human genes during one transcription cycle.
AB  - We analyzed three human genes that were >200 kbp in length as they are switched
      on rapidly and synchronously by tumor necrosis factor alpha and obtained new
      insights into the transcription cycle that are difficult to obtain using
      continuously active, short, genes. First, a preexisting "whole-gene" loop in one
      gene disappears on stimulation; it is stabilized by CCCTC-binding factor and
      TFIIB and poises the gene for a prompt response. Second, "subgene" loops
      (detected using chromosome conformation capture) develop and enlarge, a result
      that is simply explained if elongating polymerases become immobilized in
      transcription factories, where they reel in their templates. Third, high
      resolution localization confirms that relevant nascent transcripts (detected
      using RNA fluorescence in situ hybridization) lie close enough to be present on
      the surface of one factory. These dynamics underscore the complex transitions
      between the poised, initiating, and elongating transcriptional states.

PMID- 22586272
TI  - Nerve growth factor-induced cell cycle reentry in newborn neurons is triggered by
      p38MAPK-dependent E2F4 phosphorylation.
AB  - Cumulative evidence indicates that activation of cyclin D-dependent kinase 4/6
      (cdk4/6) represents a major trigger of cell cycle reentry and apoptosis in
      vertebrate neurons. We show here the existence of another mechanism triggering
      cell cycle reentry in differentiating chick retinal neurons (DCRNs), based on
      phosphorylation of E2F4 by p38(MAPK). We demonstrate that the activation of
      p75(NTR) by nerve growth factor (NGF) induces nuclear p38(MAPK) kinase activity,
      which leads to Thr phosphorylation and subsequent recruitment of E2F4 to the E2F
      responsive cdc2 promoter. Inhibition of p38(MAPK), but not of cdk4/6,
      specifically prevents NGF-dependent cell cycle reentry and apoptosis in DCRNs.
      Moreover, a constitutively active form of chick E2F4 (Thr261Glu/Thr263Glu)
      stimulates G(1)/S transition and apoptosis, even after inhibition of p38(MAPK)
      activity. In contrast, a dominant-negative E2F4 form (Thr261Ala/Thr263Ala)
      prevents NGF-induced cell cycle reactivation and cell death in DCRNs. These
      results indicate that NGF-induced cell cycle reentry in neurons depends on the
      activation of a novel, cdk4/6-independent pathway that may participate in
      neurodegeneration.

PMID- 22586274
TI  - NF-E2-related factor 1 (Nrf1) serves as a novel regulator of hepatic lipid
      metabolism through regulation of the Lipin1 and PGC-1beta genes.
AB  - Hepatic lipid metabolism is under elaborate regulation, and perturbations in this
      regulatory process at the transcriptional level lead to pathological conditions.
      NF-E2-related factor 1 (Nrf1) is a member of the cap'n'collar (CNC) transcription
      factor family. Hepatocyte-specific Nrf1 gene conditional-knockout mice are known
      to develop hepatic steatosis, but it remains unclear how Nrf1 contributes to the
      lipid homeostasis. Therefore, in this study we examined the gene expression
      profiles of Nrf1-deficient mouse livers. A pathway analysis based on the
      profiling results revealed that the levels of expression of the genes related to
      lipid metabolism, amino acid metabolism, and mitochondrial respiratory function
      were decreased in Nrf1-deficient mouse livers, indicating the profound effects
      that the Nrf1 deficiency conferred to various metabolic pathways. We discovered
      that the Nrf1 deficiency leads to the reduced expression of the transcriptional
      coactivator genes Lipin1 and PGC-1beta (for peroxisome proliferator-activated
      receptor gamma coactivator 1beta). Chromatin immunoprecipitation analyses showed
      that Nrf1 binds to the antioxidant response elements (AREs) in regulatory regions
      of the Lipin1 and PGC-1beta genes and the binding of Nrf1 to the AREs activates
      reporter gene transcription. These results thus identified Nrf1 to be a novel
      regulator of the Lipin1 and PGC-1beta genes, providing new insights into the Nrf1
      function in hepatic lipid metabolism.

PMID- 22586275
TI  - Deconstructing Ras signaling in the thymus.
AB  - Thymocytes must transit at least two distinct developmental checkpoints, governed
      by signals that emanate from either the pre-T cell receptor (pre-TCR) or the TCR
      to the small G protein Ras before emerging as functional T lymphocytes. Recent
      studies have shown a role for the Ras guanine exchange factor (RasGEF) Sos1 at
      the pre-TCR checkpoint. At the second checkpoint, the quality of signaling
      through the TCR is interrogated to ensure the production of an appropriate T cell
      repertoire. Although RasGRP1 is the only confirmed RasGEF required at the TCR
      checkpoint, current models suggest that the intensity and character of Ras
      activation, facilitated by both Sos and RasGRP1, will govern the boundary between
      survival (positive selection) and death (negative selection) at this stage. Using
      mouse models, we have assessed the independent and combined roles for the RasGEFs
      Sos1, Sos2, and RasGRP1 during thymocyte development. Although Sos1 was the
      dominant RasGEF at the pre-TCR checkpoint, combined Sos1/RasGRP1 deletion was
      required to effectively block development at this stage. Conversely, while
      RasGRP1 deletion efficiently blocked positive selection, combined RasGRP1/Sos1
      deletion was required to block negative selection. This functional redundancy in
      RasGEFs during negative selection may act as a failsafe mechanism ensuring
      appropriate central tolerance.

PMID- 22586276
TI  - The linker histone plays a dual role during gametogenesis in Saccharomyces
      cerevisiae.
AB  - The differentiation of gametes involves dramatic changes to chromatin, affecting
      transcription, meiosis, and cell morphology. Sporulation in Saccharomyces
      cerevisiae shares many chromatin features with spermatogenesis, including a 10
      fold compaction of the nucleus. To identify new proteins involved in spore
      nuclear organization, we purified chromatin from mature spores and discovered a
      significant enrichment of the linker histone (Hho1). The function of Hho1 has
      proven to be elusive during vegetative growth, but here we demonstrate its
      requirement for efficient sporulation and full compaction of the spore genome.
      Hho1 chromatin immunoprecipitation followed by sequencing (ChIP-seq) revealed
      increased genome-wide binding in mature spores and provides novel in vivo
      evidence of the linker histone binding to nucleosomal linker DNA. We also link
      Hho1 function to the transcription factor Ume6, the master repressor of early
      meiotic genes. Hho1 and Ume6 are depleted during meiosis, and analysis of
      published ChIP-chip data obtained during vegetative growth reveals a high binding
      correlation of both proteins at promoters of early meiotic genes. Moreover, Ume6
      promotes binding of Hho1 to meiotic gene promoters. Thus, Hho1 may play a dual
      role during sporulation: Hho1 and Ume6 depletion facilitates the onset of meiosis
      via activation of Ume6-repressed early meiotic genes, whereas Hho1 enrichment in
      mature spores contributes to spore genome compaction.

PMID- 22586277
TI  - Splice-mediated motif switching regulates disabled-1 phosphorylation and SH2
      domain interactions.
AB  - Disabled-1 (Dab1) plays a key role in reelin-mediated neuronal migration during
      brain development. Tyrosine phosphorylation of Dab1 at two YQXI and two YXVP
      motifs recruits multiple SH2 domains, resulting in activation of a wide range of
      signaling cascades. However, the molecular mechanisms underlying the coordinated
      regulation of Dab1 downstream effectors remain poorly understood. Here, we show
      that alternative splicing results in inclusion of different combinations of YQXI
      and YXVP motifs in Dab1 isoforms during development. Dab1 variants with partial
      or complete loss of YQXI motifs are preferentially expressed at early
      developmental stages, whereas the commonly studied Dab1 is predominantly
      expressed at late developmental stages. Expression of Dab1 variants in 293T and
      Neuro2a cells reveals reduced levels or absence of tyrosine phosphorylation in
      variants that have lost one or both YQXI motifs. We further demonstrate that Dab1
      variants differ in their abilities to activate Src and recruit distinct SH2
      domains involved in specific downstream signaling pathways. We propose that
      coordinated expression of specific Dab1 isoforms in different populations of
      cells in the developing brain contributes to precise neuronal migration by
      modulating the activity of subsets of Dab1 downstream effectors.

PMID- 22586278
TI  - Sealing the mitochondrial respirasome.
AB  - The mitochondrial respiratory chain is organized within an array of
      supercomplexes that function to minimize the generation of reactive oxygen
      species (ROS) during electron transfer reactions. Structural models of
      supercomplexes are now known. Another recent advance is the discovery of non
      OXPHOS complex proteins that appear to adhere to and seal the individual
      respiratory complexes to form stable assemblages that prevent electron leakage.
      This review highlights recent advances in our understanding of the structures of
      supercomplexes and the factors that mediate their stability.

PMID- 22586279
TI  - Ventricular assist device implantation corrects myocardial lipotoxicity, reverses
      insulin resistance, and normalizes cardiac metabolism in patients with advanced
      heart failure.
AB  - BACKGROUND: Heart failure is associated with impaired myocardial metabolism with
      a shift from fatty acids to glucose use for ATP generation. We hypothesized that
      cardiac accumulation of toxic lipid intermediates inhibits insulin signaling in
      advanced heart failure and that mechanical unloading of the failing myocardium
      corrects impaired cardiac metabolism. METHODS AND RESULTS: We analyzed the
      myocardium and serum of 61 patients with heart failure (body mass index, 26.5+/
      5.1 kg/m(2); age, 51+/-12 years) obtained during left ventricular assist device
      implantation and at explantation (mean duration, 185+/-156 days) and from 9
      control subjects. Systemic insulin resistance in heart failure was accompanied by
      decreased myocardial triglyceride and overall fatty acid content but increased
      toxic lipid intermediates, diacylglycerol, and ceramide. Increased membrane
      localization of protein kinase C isoforms, inhibitors of insulin signaling, and
      decreased activity of insulin signaling molecules Akt and Foxo were detectable in
      heart failure compared with control subjects. Left ventricular assist device
      implantation improved whole-body insulin resistance (homeostatic model of
      analysis-insulin resistance, 4.5+/-0.6-3.2+/-0.5; P<0.05) and decreased
      myocardial levels of diacylglycerol and ceramide, whereas triglyceride and fatty
      acid content remained unchanged. Improved activation of the
      insulin/phosphatidylinositol-3 kinase/Akt signaling cascade after left
      ventricular assist device implantation was confirmed by increased phosphorylation
      of Akt and Foxo, which was accompanied by decreased membrane localization of
      protein kinase C isoforms after left ventricular assist device implantation.
      CONCLUSIONS: Mechanical unloading after left ventricular assist device
      implantation corrects systemic and local metabolic derangements in advanced heart
      failure, leading to reduced myocardial levels of toxic lipid intermediates and
      improved cardiac insulin signaling.

PMID- 22586280
TI  - Chronic heart failure: a reversible metabolic syndrome?

PMID- 22586281
TI  - Short- and long-term outcomes with drug-eluting and bare-metal coronary stents: a
      mixed-treatment comparison analysis of 117 762 patient-years of follow-up from
      randomized trials.
AB  - BACKGROUND: Drug-eluting stents (DES) have been in clinical use for nearly a
      decade; however, the relative short- and long-term efficacy and safety of DES
      compared with bare-metal stents (BMS) and among the DES types are less well
      defined. METHODS AND RESULTS: PubMed, Embase, and Cochrane Central Register of
      Controlled Trials (CENTRAL) were searched for randomized clinical trials, until
      March 2012, that compared any of the Food and Drug Administration-approved
      durable stent and polymer DES (sirolimus-eluting stent [SES], paclitaxel-eluting
      stent [PES], everolimus-eluting stent [EES], zotarolimus-eluting stent [ZES], and
      ZES-Resolute [ZES-R]) with each other or against BMS for de novo coronary
      lesions, enrolling at least 100 patients and with follow-up of at least 6 months.
      Short-term (<= 1 year) and long-term efficacy (target-vessel revascularization,
      target-lesion revascularization) and safety (death, myocardial infarction, stent
      thrombosis) outcomes were evaluated and trial-level data pooled by both mixed
      treatment comparison and direct comparison analyses. From 76 randomized clinical
      trials with 117 762 patient-years of follow-up, compared with BMS, each DES
      reduced long-term target-vessel revascularization (39%-61%), but the magnitude
      varied by DES type (EES~SES~ZES-R>PES~ZES>BMS), with a >42% probability that EES
      had the lowest target-vessel revascularization rate. There was no increase in the
      risk of any long-term safety outcomes, including stent thrombosis, with any DES
      (versus BMS). In addition, there was reduction in myocardial infarction (all DES
      except PES versus BMS) and stent thrombosis (with EES versus BMS: Rate ratio,
      0.51; 95% credibility interval, 0.35-0.73). The safest DES appeared to be EES
      (>86% probability), with reduction in myocardial infarction and stent thrombosis
      compared with BMS. Short-term outcomes were similar to long-term outcomes, with
      SES, ZES-R, and everolimus-eluting stent being the most efficacious and EES being
      the safest stent. CONCLUSIONS: DES are highly efficacious at reducing the risk of
      target-vessel revascularization without an increase in any safety outcomes,
      including stent thrombosis. However, among the DES types, there were considerable
      differences, such that EES, SES, and ZES-R were the most efficacious and EES was
      the safest stent.

PMID- 22586282
TI  - Behavioural and weight status outcomes from an exploratory trial of the Healthy
      Lifestyles Programme (HeLP): a novel school-based obesity prevention programme.
AB  - OBJECTIVES: To assess the behavioural and weight status outcomes in English
      children in a feasibility study of a novel primary school-based obesity
      prevention programme. DESIGN: Exploratory cluster randomised controlled trial of
      the Healthy Lifestyles Programme. SETTING: Four city primary schools (two control
      and two intervention) in the South West of England. PARTICIPANTS: 202 children
      aged 9-10 years, of whom 193 and 188 were followed up at 18 and 24 months,
      respectively. No child was excluded from the study; however, to be eligible,
      schools were required to have at least one single Year 5 class. INTERVENTION:
      Four-phase multicomponent programme using a range of school-based activities
      including lessons, assemblies, parents' evenings, interactive drama workshops and
      goal setting to engage and support schools, children and their families in
      healthy lifestyle behaviours. It runs over the spring and summer term of Year 5
      and the autumn term of Year 6. PRIMARY AND SECONDARY OUTCOMES: Weight status
      outcomes were body mass index, waist circumference and body fat standard
      deviation scores (SDS) at 18 and 24 months, and behavioural outcomes were
      physical activity, television (TV) viewing/screen time and food intake at 18
      months. RESULTS: At 18 months of follow-up, intervention children consumed less
      energy-dense snacks and more healthy snacks; had less 'negative food markers',
      more 'positive food markers', lower mean TV/screen time and spent more time doing
      moderate-vigorous physical activity each day than those in the control schools.
      Intervention children had lower anthropometric measures at 18 and 24 months than
      control children, with larger differences at 24 months than at 18 months for
      nearly all measures. CONCLUSIONS: Results from this exploratory trial show
      consistent positive changes in favour of the intervention across all targeted
      behaviours, which, in turn, appear to affect weight status and body shape. A
      definitive trial is now justified.

PMID- 22586283
TI  - Efficacy and tolerability of a beta-1 selective beta blocker, bisoprolol, as a
      first-line antihypertensive in Indian patients diagnosed with essential
      hypertension (BRIGHT): an open-label, multicentric observational study.
AB  - OBJECTIVES: This study was aimed to evaluate the efficacy and tolerability of
      bisoprolol, in Indian patients diagnosed with stage I essential hypertension as
      first-line drug. DESIGN: This was an open-label, phase IV, multicentric
      prospective study. SETTINGS: 239 outpatient centres across India. PARTICIPANTS:
      After ethical approval, patients who were willing to sign informed consent, who
      are newly diagnosed with JNC VII stage I essential hypertension (systolic blood
      pressure 140-159 mm Hg or diastolic blood pressure 90-99 mm Hg) and who are
      prescribed bisoprolol were enrolled in the study. Patients with significant organ
      disease or complications, women of childbearing age refusing reliable
      contraceptive method, patients with known contraindications (like symptomatic
      bradycardia, significant atrioventricular blockade, sick sinus syndrome) and
      patients with known hypersensitivity reactions to bisoprolol and unwilling
      patients were excluded.   PRIMARY AND SECONDARY OUTCOMES MEASURES:  The primary
      outcome measure was percentage of patients achieving blood pressure (BP) <=140/90
      mm Hg at the end of 12 weeks, while multiple secondary outcome measures were
      assessed. RESULTS: Of 2418 patients screened, 2161 patients were recruited
      (66.64% men, mean age 51.7+/-9.8 years, smokers 19.19%) and 2131 (96.44%)
      patients achieved BP control. There was significant reduction in systolic blood
      pressure (-25.29; SD: 13.22 mm Hg), diastolic blood pressure (-14.14; SD: 7.67 mm
      Hg) and heart rate (-12/min; SD: 6.15) compared with baseline (all p values
      <0.05). The median dose of bisoprolol and average period required for the
      response were 5 mg/day and 33 days, respectively. Bisoprolol was found to be well
      tolerated in the patients up to 10 mg/day. A total of 1.9% patients showed
      adverse events, which were mild to moderate in severity without any severe
      adverse event. None required treatment withdrawal. CONCLUSION: Bisoprolol is an
      effective and safe option to control BP. Thus, it can be used as one of the first
      line antihypertensive in Indian patients.

PMID- 22586284
TI  - Effect of a school-based peer education intervention on physical activity and
      sedentary behaviour in Chinese adolescents: a pilot study.
AB  - OBJECTIVE: To evaluate the effect on physical activity and sedentary behaviour of
      a pilot school-based peer education programme in urban Beijing, China. DESIGN: 4
      junior high schools were matched by school size and randomised to intervention
      (n=346) and control group (n=336). INTERVENTION: Trained peer leaders from grade
      7 by research staff delivered weekly 40-min lessons to their classmates over four
      consecutive weeks. Students in control schools received no intervention. OUTCOME
      MEASURES: A validated 7-day youth physical activity questionnaire was used to
      evaluate physical activity and sedentary behaviours at baseline (September 2010),
      3 months (December 2010) and 7 months (May 2011). Generalised linear mixed models
      were applied to evaluate the effect. RESULTS: There was a significant decrease in
      time in sedentary behaviour on weekdays, 20 min/day at 7 months (p=0.020)
      reported by students in the intervention schools compared with control schools.
      This reduction was mainly due to a reduction of 14 min/day in computer usage on
      weekdays (p=0.0009). There were no significant differences in time on other
      sedentary behaviours, including television and DVD, video game, extracurricular
      reading, writing, drawing and listening to music, passive commuting and sitting
      to talk. There was also no significant difference in time in moderate-to-vigorous
      physical activity between intervention and control group. CONCLUSIONS: Peer
      education appears to be a promising intervention in reducing sedentary behaviours
      in adolescents in China. These results need confirmation in a larger study.
      CLINICAL TRIAL REGISTRATION NUMBER: ACTRN12612000417886 at http://ANZCTR.org.au.

PMID- 22586285
TI  - Worldwide impact of economic cycles on suicide trends over 3 decades: differences
      according to level of development. A mixed effect model study.
AB  - OBJECTIVES: To investigate the trends and correlations of gross domestic product
      (GDP) adjusted for purchasing power parity (PPP) per capita on suicide rates in
      10 WHO regions during the past 30 years. DESIGN: Analyses of databases of PPP
      adjusted GDP per capita and suicide rates. Countries were grouped according to
      the Global Burden of Disease regional classification system. DATA SOURCES: World
      Bank's official website and WHO's mortality database. STATISTICAL ANALYSES: After
      graphically displaying PPP-adjusted GDP per capita and suicide rates, mixed
      effect models were used for representing and analysing clustered data. RESULTS:
      Three different groups of countries, based on the correlation between the PPP
      adjusted GDP per capita and suicide rates, are reported: (1) positive
      correlation: developing (lower middle and upper middle income) Latin-American and
      Caribbean countries, developing countries in the South East Asian Region
      including India, some countries in the Western Pacific Region (such as China and
      South Korea) and high-income Asian countries, including Japan; (2) negative
      correlation: high-income and developing European countries, Canada, Australia and
      New Zealand and (3) no correlation was found in an African country. CONCLUSIONS:
      PPP-adjusted GDP per capita may offer a simple measure for designing the type of
      preventive interventions aimed at lowering suicide rates that can be used across
      countries. Public health interventions might be more suitable for developing
      countries. In high-income countries, however, preventive measures based on the
      medical model might prove more useful.

PMID- 22586286
TI  - Understanding public trust in services provided by community pharmacists relative
      to those provided by general practitioners: a qualitative study.
AB  - OBJECTIVES: To apply sociological theories to understand public trust in extended
      services provided by community pharmacists relative to those provided by general
      practitioners (GPs). DESIGN: Qualitative study involving focus groups with
      members of the public. SETTING: The West of Scotland. PARTICIPANTS: 26
      purposively sampled members of the public were involved in one of five focus
      groups. The groups were composed to represent known groups of users and non-users
      of community pharmacy, namely mothers with young children, seniors and men.
      RESULTS: Trust was seen as being crucial in healthcare settings. Focus group
      discussions revealed that participants were inclined to draw unfavourable
      comparisons between pharmacists and GPs. Importantly, participants' trust in GPs
      was greater than that in pharmacists. Participants considered pharmacists to be
      primarily involved in medicine supply, and awareness of the pharmacist's extended
      role was low. Participants were often reluctant to trust pharmacists to deliver
      unfamiliar services, particularly those perceived to be 'high risk'. Numerous
      system-based factors were identified, which reinforce patient trust and
      confidence in GPs, including GP registration and appointment systems, GPs'
      expert/gatekeeper role and practice environments. Our data indicate that the
      nature and context of public interactions with GPs fostered familiarity with a
      specific GP or practice, which allowed interpersonal trust to develop. By
      contrast, participants' exposure to community pharmacists was limited.
      Additionally, a good understanding of the GPs' level of training and role
      promoted confidence. CONCLUSION: Current UK initiatives, which aim to implement a
      range of pharmacist-led services, are undermined by lack of public trust. It
      seems improbable that the public will trust pharmacists to deliver unfamiliar
      services, which are perceived to be 'high risk', unless health systems change in
      a way that promotes trust in pharmacists. This may be achieved by increasing the
      quality and quantity of patient interactions with pharmacists and gaining GP
      support for extended pharmacy services.

PMID- 22586287
TI  - A four-country survey of public attitudes towards restricting healthcare costs by
      limiting the use of high-cost medical interventions.
AB  - OBJECTIVE: To discern how the public in four countries, each with unique health
      systems and cultures, feels about efforts to restrain healthcare costs by
      limiting the use of high-cost prescription drugs and medical/surgical treatments.
      DESIGN: Cross-sectional survey. SETTING: Adult populations in Germany, Italy, the
      UK and the USA. PARTICIPANTS: 2517 adults in the four countries. A questionnaire
      survey conducted by telephone (landline and cell) with randomly selected adults
      in each of the four countries. MAIN OUTCOME MEASURES: Support for different
      rationales for not providing/paying for high-cost prescription drugs/medical or
      surgical treatments, measured in the aggregate and using four case examples
      derived from actual decisions. Measures of public attitudes about specific
      policies involving comparative effectiveness and cost-benefit decision making.
      RESULTS: The survey finds support among publics in four countries for decisions
      that limit the use of high-cost prescription drugs/treatments when some other
      drug/treatment is available that works equally well but costs less. The survey
      finds little public support, either in individual case examples or when asked in
      the aggregate, for decisions in which prescription drugs/treatments are denied on
      the basis of cost or various definitions of benefits. The main results are based
      on majorities of the public in each country supporting or opposing each measure.
      CONCLUSIONS: The survey findings indicate that the public distinguishes in
      practice between the concepts of comparative effectiveness and cost-effectiveness
      analysis. This suggests that public authorities engaged in decision-making
      activities will find much more public support if they are dealing with the first
      type of decision than with the second.

PMID- 22586288
TI  - Observational study on factors related to health-promoting community activity
      development in primary care (frAC Project): a study protocol.
AB  - INTRODUCTION: According to Spanish health regulations, primary care professionals
      have the responsibility to carry out health-promoting community activities (CAs).
      However, in practice, their implementation is not as widespread as it should be.
      The aims of this study were to identify factors within the team, the community
      and the professionals that influence the development of these activities and to
      describe the community interventions in progress. METHODS AND ANALYSIS: This
      study is an observational analytical retrospective study. The information will be
      collected from five Spanish regions: Catalonia, Madrid, the Balearic Islands,
      Navarra and Aragon. The authors will contact primary care teams (PCTs) and
      identify the CAs from the previous year. The research team will conduct a peer
      review whether the inclusion criteria are met. In the health centres where CAs
      are implemented, the authors will select professionals carrying them out and
      randomly select an identical number of professionals not doing these activities.
      In the centres where no CA is implemented, three professionals will be randomly
      selected. The selected professionals will complete the questionnaires for
      individual-level variables. Information about the registered population and the
      PCTs will be collected through questionnaires and secondary sources. OUTCOMES:
      Variables will be collected from the community, the PCTs, the individual
      professionals and CAs. ANALYSIS: A descriptive analysis of all the variables will
      be carried out, along with a bivariate and a logistic regression analysis, with
      CAs being the primary outcome. ETHICS AND DISSEMINATION: This study has been
      approved by the Research Ethics Committee of the Jordi Gol y Gurina Foundation in
      Barcelona and area 11 in Madrid. The questionnaire distributed to the
      professionals will be anonymous.

PMID- 22586289
TI  - Molecular characterization of folate receptor 1 mutations delineates cerebral
      folate transport deficiency.
AB  - Cerebral folate transport deficiency is an inherited brain-specific folate
      transport defect that is caused by mutations in the folate receptor 1 gene coding
      for folate receptor alpha (FRalpha). This genetic defect gives rise to a
      progressive neurological disorder with late infantile onset. We screened 72
      children with low 5-methyltetrahydrofolate concentrations in the cerebrospinal
      fluid and neurological symptoms that developed after infancy. We identified
      nucleotide alterations in the folate receptor 1 gene in 10 individuals who shared
      developmental regression, ataxia, profound cerebral hypomyelination and
      cerebellar atrophy. We found four novel pathogenic alleles, one splice mutation
      and three missense mutations. Heterologous expression of the missense mutations,
      including previously described mutants, revealed minor decrease in protein
      expression but loss of cell surface localization, mistargeting to intracellular
      compartments and thus absence of cellular binding of folic acid. These results
      explain the functional loss of folate receptor alpha for all detected folate
      receptor 1 mutations. Three individuals presenting a milder clinical phenotype
      revealed very similar biochemical and brain imaging data but partially shared
      pathogenic alleles with more severely affected patients. Thus, our studies
      suggest that different clinical severities do not necessarily correlate with
      residual function of folate receptor alpha mutants and indicate that additional
      factors contribute to the clinical phenotype in cerebral folate transport
      deficiency.

PMID- 22586290
TI  - Georg Ohm and the changing character of aortic stenosis: it's not your
      grandfather's oldsmobile.

PMID- 22586291
TI  - Primary prevention of atherosclerosis: a clinical challenge for the reversal of
      epigenetic mechanisms?

PMID- 22586292
TI  - Pediatric out-of-hospital cardiac arrest.

PMID- 22586293
TI  - Recurrent inflammatory myofibroblastic tumor of the heart.

PMID- 22586294
TI  - Successful Fontan completion after cardiac resynchronization therapy.

PMID- 22586296
TI  - Letter by Farmakis and Aessopos regarding article, "echocardiographic markers of
      elevated pulmonary pressure and left ventricular diastolic dysfunction are
      associated with exercise intolerance in adults and adolescents with homozygous
      sickle cell anemia in the United States and United kingdom".

PMID- 22586297
TI  - Letter by Kuller and Wong regarding article, "comparative effectiveness of
      exercise electrocardiography with or without myocardial perfusion single photon
      emission computed tomography in women with suspected coronary artery disease:
      results from the What Is the Optimal Method for Ischemia Evaluation in Women
      (WOMEN) trial".

PMID- 22586298
TI  - Letter by Palmas regarding article, "comparative effectiveness of exercise
      electrocardiography with or without myocardial perfusion single photon emission
      computed tomography in women with suspected coronary artery disease: results from
      the What Is the Optimal Method for Ischemia Evaluation in Women (WOMEN) trial".

PMID- 22586299
TI  - Letter by Heston regarding article, "comparative effectiveness of exercise
      electrocardiography with or without myocardial perfusion single photon emission
      computed tomography in women with suspected coronary artery disease: results from
      the What Is the Optimal Method for Ischemia Evaluation in Women (WOMEN) trial".

PMID- 22586300
TI  - GDC-0941, a novel class I selective PI3K inhibitor, enhances the efficacy of
      docetaxel in human breast cancer models by increasing cell death in vitro and in
      vivo.
AB  - PURPOSE: Docetaxel is a front-line standard-of-care chemotherapeutic drug for the
      treatment of breast cancer. Phosphoinositide 3-kinases (PI3K) are lipid kinases
      that regulate breast tumor cell growth, migration, and survival. The current
      study was intended to determine whether GDC-0941, an orally bioavailable class I
      selective PI3K inhibitor, enhances the antitumor activity of docetaxel in human
      breast cancer models in vitro and in vivo. EXPERIMENTAL DESIGN: A panel of 25
      breast tumor cell lines representing HER2+, luminal, and basal subtypes were
      treated with GDC-0941, docetaxel, or the combination of both drugs and assayed
      for cellular viability, modulation of PI3K pathway markers, and apoptosis
      induction. Drug combination effects on cellular viability were also assessed in
      nontransformed MCF10A human mammary epithelial cells. Human xenografts of breast
      cancer cell lines and patient-derived tumors were used to assess efficacy of GDC
      0941 and docetaxel in vivo. RESULTS: Combination of GDC-0941 and docetaxel
      decreased the cellular viability of breast tumor cell lines in vitro but to
      variable degrees of drug synergy. Compared with nontransformed MCF10A cells, the
      addition of both drugs resulted in stronger synergistic effects in a subset of
      tumor cell lines that were not predicted by breast cancer subtype. In xenograft
      models, GDC-0941 enhanced the antitumor activity of docetaxel with maximum
      combination efficacy observed within 1 hour of administering both drugs. GDC-0941
      increased the rate of apoptosis in cells arrested in mitosis upon cotreatment
      with docetaxel. CONCLUSION: GDC-0941 augments the efficacy of docetaxel by
      increasing drug-induced apoptosis in breast cancer models.

PMID- 22586302
TI  - The era of cancer discovery.

PMID- 22586307
TI  - Update from the Hill: budget battle.

PMID- 22586301
TI  - Targeted inhibition of Src kinase with dasatinib blocks thyroid cancer growth and
      metastasis.
AB  - PURPOSE: There are no effective therapies for patients with poorly differentiated
      papillary thyroid cancer (PTC) or anaplastic thyroid cancer (ATC), and metastasis
      to the bone represents a significantly worse prognosis. Src family kinases (SFKs)
      are overexpressed and activated in numerous tumor types and have emerged as a
      promising therapeutic target, especially in relation to metastasis. We recently
      showed that Src is overexpressed and activated in thyroid cancer. We therefore
      tested whether inhibition of Src with dasatinib (BMS-354825) blocks thyroid
      cancer growth and metastasis. EXPERIMENTAL DESIGN: The effects of dasatinib on
      thyroid cancer growth, signaling, cell cycle, and apoptosis were evaluated in
      vitro. The therapeutic efficacy of dasatinib was further tested in vivo using an
      orthotopic and a novel experimental metastasis model. Expression and activation
      of SFKs in thyroid cancer cells was characterized, and selectivity of dasatinib
      was determined using an Src gatekeeper mutant. RESULTS: Dasatinib treatment
      inhibited Src signaling, decreased growth, and induced cell-cycle arrest and
      apoptosis in a subset of thyroid cancer cells. Immunoblotting showed that c-Src
      and Lyn are expressed in thyroid cancer cells and that c-Src is the predominant
      SFK activated. Treatment with dasatinib blocked PTC tumor growth in an orthotopic
      model by more than 90% (P = 0.0014). Adjuvant and posttreatment approaches with
      dasatinib significantly inhibited metastasis (P = 0.016 and P = 0.004,
      respectively). CONCLUSION: These data provide the first evidence that Src is a
      central mediator of thyroid cancer growth and metastasis, indicating that Src
      inhibitors may have a higher therapeutic efficacy in thyroid cancer, as both
      antitumor and antimetastatic agents.

PMID- 22586312
TI  - KRAS oncogene rearrangements and gene fusions: unexpected rare encounters in late
      stage prostate cancers.
AB  - Wang and colleagues identify a fusion between UBE2L3 and KRAS in a subset of
      metastatic prostate cancers.

PMID- 22586313
TI  - A new BATTLE in the evolving war on cancer.
AB  - The Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer
      Elimination (BATTLE) trial couples real-time molecular interrogation of cancer
      specimens with an adaptive Bayesian clinical trial design.

PMID- 22586314
TI  - The BATTLE trial: a bold step toward improving the efficiency of biomarker-based
      drug development.
AB  - Successful completion of the Biomarker-integrated Approaches of Targeted Therapy
      for Lung Cancer Elimination (BATTLE) trial, reported in this issue of Cancer
      Discovery, is an important advance in the effort to improve clinical trial
      approaches to the simultaneous development of new therapeutics with matching
      diagnostic tests so that patients most likely to benefit from these therapies can
      be identified.

PMID- 22586315
TI  - Epidemiology--found in translation.
AB  - We highlight the value of carefully designed observational epidemiologic analyses
      in translating basic science discoveries to clinical application and in providing
      the impetus for exploring underlying mechanisms for observed associations.
      Coupling epidemiologic data with an in vitro screen of commonly used therapeutic
      agents may identify novel applications for further clinical testing.

PMID- 22586316
TI  - A new target for therapy in squamous cell carcinoma of the lung.
AB  - Investigators report the identification of novel somatic mutations in the DDR2
      kinase gene in squamous cell carcinoma of the lung. Cellular, biochemical, and
      human data suggest that tumor cells harboring DDR2 mutations have increased
      sensitivity to existing tyrosine kinase inhibitors, providing rationale for
      clinical trials of agents that inhibit DDR2 kinase in the disease.

PMID- 22586317
TI  - Toward molecular imaging-driven drug development in oncology.
AB  - With current testing strategies, the number of novel targeted anticancer agents
      will exceed our drug selection capacity. Molecular imaging is a powerful
      additional tool that can assist us in selecting effective drugs and help patients
      benefit from targeted agents. Moreover, measurement of the functional effects of
      such targeted agents could permit dynamic tuning of treatment selection at the
      earliest time point at which loss of functional effects is observed.

PMID- 22586318
TI  - Stumbling blocks on the path to personalized medicine in breast cancer: the case
      of PARP inhibitors for BRCA1/2-associated cancers.
AB  - The popular vision for the future of oncology includes the rational design of
      therapies inhibiting specific targets, for which development would be less
      expensive and the chance of success greater because the agent, the target, and a
      population predicted to benefit maximally would be known from the outset. In the
      breast cancer arena, successful targeted therapies have entered clinical
      practice. Recently, patients with BRCA-associated cancers have been identified as
      eligible for novel investigational therapies targeting their genetic deficiency.
      Preclinical data, phase I results, and 2 phase II proof-of-concept studies
      support the continued development of PARP inhibitors, either as single agents or
      in combination with specific cytotoxic drugs in this setting. In this article, we
      provide a brief review of current developments concerning PARP inhibitors in BRCA
      associated cancers and express concerns about challenges to further development.
      SUMMARY: PARP inhibitors may represent a new and promising targeted therapy for
      patients with BRCA1/2 -associated cancer. In this review we summarize the main
      challenges in the clinical development of these agents.

PMID- 22586324
TI  - Counterpoint: enough evidence to treat? The American College of Obstetricians and
      Gynecologists guidelines.

PMID- 22586319
TI  - The BATTLE trial: personalizing therapy for lung cancer.
AB  - The Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer
      Elimination (BATTLE) trial represents the first completed prospective, biopsy
      mandated, biomarker-based, adaptively randomized study in 255 pretreated lung
      cancer patients. Following an initial equal randomization period, chemorefractory
      non-small cell lung cancer (NSCLC) patients were adaptively randomized to
      erlotinib, vandetanib, erlotinib plus bexarotene, or sorafenib, based on relevant
      molecular biomarkers analyzed in fresh core needle biopsy specimens. Overall
      results include a 46% 8-week disease control rate (primary end point), confirm
      prespecified hypotheses, and show an impressive benefit from sorafenib among
      mutant-KRAS patients. BATTLE establishes the feasibility of a new paradigm for a
      personalized approach to lung cancer clinical trials. SIGNIFICANCE: The BATTLE
      study is the first completed prospective, adaptively randomized study in heavily
      pretreated NSCLC patients that mandated tumor profiling with "real-time"
      biopsies, taking a substantial step toward realizing personalized lung cancer
      therapy by integrating real-time molecular laboratory findings in delineating
      specific patient populations for individualized treatment.

PMID- 22586325
TI  - Binding of hepcidin to plasma proteins.

PMID- 22586327
TI  - Divergent evolutionary pattern of starch biosynthetic pathway genes in grasses
      and dicots.
AB  - Starch is the most widespread and abundant storage carbohydrate in crops and its
      production is critical to both crop yield and quality. In regard to the starch
      content in the seeds of crop plants, there is a distinct difference between
      grasses (Poaceae) and dicots. However, few studies have described the
      evolutionary pattern of genes in the starch biosynthetic pathway in these two
      groups of plants. In this study, therefore, an attempt was made to compare
      evolutionary rate, gene duplication, and selective pattern of the key genes
      involved in this pathway between the two groups, using five grasses and five
      dicots as materials. The results showed 1) distinct differences in patterns of
      gene duplication and loss between grasses and dicots; duplication in grasses
      mainly occurred before the divergence of grasses, whereas duplication mostly
      occurred in individual species within the dicots; there is less gene loss in
      grasses than in dicots, 2) a considerably higher evolutionary rate in grasses
      than in dicots in most gene families analyzed, and 3) evidence of a different
      selective pattern between grasses and dicots; positive selection may have
      occurred asymmetrically in grasses in some gene families, for example, ADP
      glucose pyrophosphorylase small subunit. Therefore, we deduced that gene
      duplication contributes to, and a higher evolutionary rate is associated with,
      the higher starch content in grasses. In addition, two novel aspects of the
      evolution of the starch biosynthetic pathway were observed.

PMID- 22586326
TI  - Functional proteomics establishes the interaction of SIRT7 with chromatin
      remodeling complexes and expands its role in regulation of RNA polymerase I
      transcription.
AB  - Among mammalian sirtuins, SIRT7 is the only enzyme residing in nucleoli where
      ribosomal DNA is transcribed. Recent reports established that SIRT7 associates
      with RNA Pol I machinery and is required for rDNA transcription. Although defined
      by its homology to the yeast histone deacetylase Sir2, current knowledge suggests
      that SIRT7 itself has little to no deacetylase activity. Because only two SIRT7
      interactions have been thus far described: RNA Pol I and upstream binding factor,
      identification of proteins and complexes associating with SIRT7 is critical to
      understanding its functions. Here, we present the first characterization of SIRT7
      interaction networks. We have systematically investigated protein interactions of
      three EGFP-tagged SIRT7 constructs: wild type, a point mutation affecting rDNA
      transcription, and a deletion mutant lacking the predicted coiled-coil domain. A
      combinatorial proteomics and bioinformatics approach was used to integrate gene
      ontology classifications, functional protein networks, and normalized abundances
      of proteins co-isolated with SIRT7. The resulting refined proteomic data set
      confirmed SIRT7 interactions with RNA Pol I and upstream binding factor and
      highlighted association with factors involved in RNA Pol I- and II-dependent
      transcriptional processes and several nucleolus-localized chromatin remodeling
      complexes. Particularly enriched were members of the B-WICH complex, such as
      Mybbp1a, WSTF, and SNF2h. Prominent interactions were validated by a selected
      reaction monitoring-like approach using metabolic labeling with stable isotopes,
      confocal microscopy, reciprocal immunoaffinity precipitation, and co-isolation
      with endogenous SIRT7. To extend the current knowledge of mechanisms involved in
      SIRT7-dependent regulation of rDNA transcription, we showed that small
      interfering RNA-mediated SIRT7 knockdown leads to reduced levels of RNA Pol I
      protein, but not messenger RNA, which was confirmed in diverse cell types. The
      down-regulation of RNA Pol I protein levels placed in the context of SIRT7
      interaction networks led us to propose that SIRT7 plays a crucial role in
      connecting the function of chromatin remodeling complexes to RNA Pol I machinery
      during transcription.

PMID- 22586328
TI  - Habitat variability correlates with duplicate content of Drosophila genomes.
AB  - The factors limiting the habitat range of species are crucial in understanding
      their biodiversity and response to environmental change. Yet the genetic and
      genomic architectures that produce genetic variation to enable environmental
      adaptation have remained poorly understood. Here we show that the proportion of
      duplicated genes (P(D)) in the whole genomes of fully sequenced Drosophila
      species is significantly correlated with environmental variability within the
      habitats measured by the climatic envelope and habitat diversity. Furthermore,
      species with a low P(D) tend to lose the duplicated genes owing to their faster
      evolution. These results indicate that the rapid relaxation of functional
      constraints on duplicated genes resulted in a low P(D) for species with lower
      habitat diversity, and suggest that the maintenance of duplicated genes gives
      organisms an ecological advantage during evolution. We therefore propose that the
      P(D) in a genome is related to adaptation to environmental variation.

PMID- 22586329
TI  - Medical ink.

PMID- 22586330
TI  - Managing obesity in adults in primary care.

PMID- 22586332
TI  - Diabetes registry overdue, if not obsolete.

PMID- 22586333
TI  - Statistical starting points in Africa.

PMID- 22586331
TI  - The prognosis of acute and persistent low-back pain: a meta-analysis.
AB  - BACKGROUND: Although low-back pain is a highly prevalent condition, its clinical
      course remains uncertain. Our main objective was to systematically review the
      literature on the clinical course of pain and disability in patients with acute
      and persistent low-back pain. Our secondary objective was to investigate whether
      pain and disability have similar courses. METHODS: We performed a meta-analysis
      of inception cohort studies. We identified eligible studies by searching MEDLINE,
      Embase and CINAHL. We included prospective studies that enrolled an episode
      inception cohort of patients with acute or persistent low-back pain and that
      measured pain, disability or recovery. Two independent reviewers extracted data
      and assessed methodologic quality. We used mixed models to determine pooled
      estimates of pain and disability over time. RESULTS: Data from 33 discrete
      cohorts (11 166 participants) were included in the review. The variance-weighted
      mean pain score (out of a maximum score of 100) was 52 (95% CI 48-57) at
      baseline, 23 (95% CI 21-25) at 6 weeks, 12 (95% CI 9-15) at 26 weeks and 6 (95%
      CI 3-10) at 52 weeks after the onset of pain for cohorts with acute pain. Among
      cohorts with persistent pain, the variance-weighted mean pain score (out of 100)
      was 51 (95% CI 44-59) at baseline, 33 (95% CI 29-38) at 6 weeks, 26 (95% CI 20
      33) at 26 weeks and 23 (95% CI 16-30) at 52 weeks after the onset of pain. The
      course of disability outcomes was similar to the time course of pain outcomes in
      the acute pain cohorts, but the pain outcomes were slightly worse than disability
      outcomes in the persistent pain cohorts. INTERPRETATION: Patients who presented
      with acute or persistent low-back pain improved markedly in the first six weeks.
      After that time improvement slowed. Low to moderate levels of pain and disability
      were still present at one year, especially in the cohorts with persistent pain.

PMID- 22586334
TI  - Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo
      controlled trial.
AB  - BACKGROUND: Spasticity is a common and poorly controlled symptom of multiple
      sclerosis. Our objective was to determine the short-term effect of smoked
      cannabis on this symptom. METHODS: We conducted a placebo-controlled, crossover
      trial involving adult patients with multiple sclerosis and spasticity. We
      recruited participants from a regional clinic or by referral from specialists. We
      randomly assigned participants to either the intervention (smoked cannabis, once
      daily for three days) or control (identical placebo cigarettes, once daily for
      three days). Each participant was assessed daily before and after treatment.
      After a washout interval of 11 days, participants crossed over to the opposite
      group. Our primary outcome was change in spasticity as measured by patient score
      on the modified Ashworth scale. Our secondary outcomes included patients'
      perception of pain (as measured using a visual analogue scale), a timed walk and
      changes in cognitive function (as measured by patient performance on the Paced
      Auditory Serial Addition Test), in addition to ratings of fatigue. RESULTS:
      Thirty-seven participants were randomized at the start of the study, 30 of whom
      completed the trial. Treatment with smoked cannabis resulted in a reduction in
      patient scores on the modified Ashworth scale by an average of 2.74 points more
      than placebo (p < 0.0001). In addition, treatment reduced pain scores on a visual
      analogue scale by an average of 5.28 points more than placebo (p = 0.008). Scores
      for the timed walk did not differ significantly between treatment and placebo (p
      = 0.2). Scores on the Paced Auditory Serial Addition Test decreased by 8.67
      points more with treatment than with placebo (p = 0.003). No serious adverse
      events occurred during the trial. INTERPRETATION: Smoked cannabis was superior to
      placebo in symptom and pain reduction in participants with treatment-resistant
      spasticity. Future studies should examine whether different doses can result in
      similar beneficial effects with less cognitive impact.

PMID- 22586335
TI  - Cushing syndrome due to ritonavir-fluticasone interaction.

PMID- 22586337
TI  - A Jehovah's Witness adolescent with pancytopenia.

PMID- 22586338
TI  - Prognosis in people with back pain.

PMID- 22586339
TI  - Mental health strategy needs national buy-in.

PMID- 22586340
TI  - Genetic literacy poor in primary care.

PMID- 22586346
TI  - Drug discovery gets an academic push.

PMID- 22586351
TI  - Kras, Pten, NF-kappaB, and inflammation: dangerous liaisons.
AB  - Ying and colleagues identify a novel function of Pten as a haploinsufficient
      tumor suppressor in human pancreatic cancer development. Genomic, genetic, and
      biochemical data reveal that Pten loss and Kras mutation cooperate to accelerate
      pancreatic cancer development by altering PI3K regulation to enhance NF-kappaB
      activation and upregulate downstream cytokine genes; this provides a
      protumorigenic and metastatic microenvironment.

PMID- 22586352
TI  - New routes to old places: PIK3R1 and PIK3R2 join PIK3CA and PTEN as endometrial
      cancer genes.
AB  - Cheung and colleagues identify PIK3R1 and PIK3R2, the genes encoding the alpha
      and beta isoforms of the phosphatidylinositol 3-kinase (PI3K) p85 regulatory
      subunit, as additional mutation targets in endometrial cancer, and describe a
      novel mechanism leading to PTEN loss.

PMID- 22586354
TI  - The drug-induced degradation of oncoproteins: an unexpected Achilles' heel of
      cancer cells?
AB  - Many targeted therapies against cancer are aimed at inhibiting the enzymatic
      activity of kinases. Thus far, this approach has undoubtedly yielded significant
      clinical improvements, but has only rarely achieved cures. Other drugs, which
      selectively elicit proteasome-dependent degradation of oncoproteins, induce the
      loss of cancer cell self-renewal and promote cell differentiation and/or
      apoptosis. In acute promyelocytic leukemia, the cooperative degradation of
      PML/RARA by arsenic and retinoic acid cures most patients. In this condition and
      others, drug-induced proteolysis of oncoproteins is feasible and underlies
      improved clinical outcome. Several transcription factors, nuclear receptors, or
      fusion proteins driving cancer growth could be candidates for proteolysis-based
      drug-discovery programs.

PMID- 22586355
TI  - Deformation measurement of individual cells in large populations using a single
      cell microchamber array chip.
AB  - We analyze the deformability of individual red blood cells (RBCs) using SiCMA
      technology. Our approach is adequate to quickly measure large numbers of
      individual cells in heterogeneous populations. Individual cells are trapped in a
      large-scale array of micro-wells, and dielectrophoretic (DEP) force is applied to
      deform the cells. The simple structures of micro-wells and DEP electrodes
      facilitate the analysis of thousands of RBCs in parallel. This unique method
      allows the correlation of red cell deformation with cell surface and cytosolic
      characteristics to define the distribution of individual cellular characteristics
      in heterogeneous populations.

PMID- 22586356
TI  - Adaptively deformed mesh based interface method for elliptic equations with
      discontinuous coefficients.
AB  - Mesh deformation methods are a versatile strategy for solving partial
      differential equations (PDEs) with a vast variety of practical applications.
      However, these methods break down for elliptic PDEs with discontinuous
      coefficients, namely, elliptic interface problems. For this class of problems,
      the additional interface jump conditions are required to maintain the well
      posedness of the governing equation. Consequently, in order to achieve high
      accuracy and high order convergence, additional numerical algorithms are required
      to enforce the interface jump conditions in solving elliptic interface problems.
      The present work introduces an interface technique based adaptively deformed mesh
      strategy for resolving elliptic interface problems. We take the advantages of the
      high accuracy, flexibility and robustness of the matched interface and boundary
      (MIB) method to construct an adaptively deformed mesh based interface method for
      elliptic equations with discontinuous coefficients. The proposed method generates
      deformed meshes in the physical domain and solves the transformed governed
      equations in the computational domain, which maintains regular Cartesian meshes.
      The mesh deformation is realized by a mesh transformation PDE, which controls the
      mesh redistribution by a source term. The source term consists of a monitor
      function, which builds in mesh contraction rules. Both interface geometry based
      deformed meshes and solution gradient based deformed meshes are constructed to
      reduce the L(infinity) and L(2) errors in solving elliptic interface problems.
      The proposed adaptively deformed mesh based interface method is extensively
      validated by many numerical experiments. Numerical results indicate that the
      adaptively deformed mesh based interface method outperforms the original MIB
      method for dealing with elliptic interface problems.

PMID- 22586357
TI  - Different evolutionary modifications as a guide to rewire two-component systems.
AB  - Two-component systems (TCS) are short signalling pathways generally occurring in
      prokaryotes. They frequently regulate prokaryotic stimulus responses and thus are
      also of interest for engineering in biotechnology and synthetic biology. The aim
      of this study is to better understand and describe rewiring of TCS while
      investigating different evolutionary scenarios. Based on large-scale screens of
      TCS in different organisms, this study gives detailed data, concrete alignments,
      and structure analysis on three general modification scenarios, where TCS were
      rewired for new responses and functions: (i) exchanges in the sequence within
      single TCS domains, (ii) exchange of whole TCS domains; (iii) addition of new
      components modulating TCS function. As a result, the replacement of stimulus and
      promotor cassettes to rewire TCS is well defined exploiting the alignments given
      here. The diverged TCS examples are non-trivial and the design is challenging.
      Designed connector proteins may also be useful to modify TCS in selected cases.

PMID- 22586359
TI  - Development of the corticothalamic projections.
AB  - In this review we discuss recent advances in the understanding of corticothalamic
      axon guidance; patterning of the early telencephalon, the sequence and
      choreography of the development of projections from subplate, layers 5 and 6.
      These cortical subpopulations display different axonal outgrowth kinetics and
      innervate distinct thalamic nuclei in a temporal pattern determined by cortical
      layer identity and subclass specificity. Guidance by molecular cues, structural
      cues, and activity-dependent mechanisms contribute to this development. There is
      a substantial rearrangement of the corticofugal connectivity outside the thalamus
      at the border of and within the reticular thalamic nucleus, a region that shares
      some of the characteristics of the cortical subplate during development. The
      early transient circuits are not well understood, nor the extent to which this
      developmental pattern may be driven by peripheral sensory activity. We
      hypothesize that transient circuits during embryonic and early postnatal
      development are critical in the matching of the cortical and thalamic
      representations and forming the cortical circuits in the mature brain.

PMID- 22586360
TI  - Why Some People Discount More than Others: Baseline Activation in the Dorsal PFC
      Mediates the Link between COMT Genotype and Impatient Choice.
AB  - Individuals differ widely in how steeply they discount future rewards. The
      sources of these stable individual differences in delay discounting (DD) are
      largely unknown. One candidate is the COMT Val158Met polymorphism, known to
      modulate prefrontal dopamine levels and affect DD. To identify possible neural
      mechanisms by which this polymorphism may contribute to stable individual DD
      differences, we measured 73 participants' neural baseline activation using
      resting electroencephalogram (EEG). Such neural baseline activation measures are
      highly heritable and stable over time, thus an ideal endophenotype candidate to
      explain how genes may influence behavior via individual differences in neural
      function. After EEG-recording, participants made a series of incentive-compatible
      intertemporal choices to determine the steepness of their DD. We found that COMT
      significantly affected DD and that this effect was mediated by baseline
      activation level in the left dorsal prefrontal cortex (DPFC): (i) COMT had a
      significant effect on DD such that the number of Val alleles was positively
      correlated with steeper DD (higher numbers of Val alleles means greater COMT
      activity and thus lower dopamine levels). (ii) A whole-brain search identified a
      cluster in left DPFC where baseline activation was correlated with DD; lower
      activation was associated with steeper DD. (iii) COMT had a significant effect on
      the baseline activation level in this left DPFC cluster such that a higher number
      of Val alleles was associated with lower baseline activation. (iv) The effect of
      COMT on DD was explained by the mediating effect of neural baseline activation in
      the left DPFC cluster. Our study thus establishes baseline activation level in
      left DPFC as salient neural signature in the form of an endophenotype that
      mediates the link between COMT and DD.

PMID- 22586362
TI  - Comparison of dry and gel based electrodes for p300 brain-computer interfaces.
AB  - Most brain-computer interfaces (BCIs) rely on one of three types of signals in
      the electroencephalogram (EEG): P300s, steady-state visually evoked potentials,
      and event-related desynchronization. EEG is typically recorded non-invasively
      with electrodes mounted on the human scalp using conductive electrode gel for
      optimal impedance and data quality. The use of electrode gel entails serious
      problems that are especially pronounced in real-world settings when experts are
      not available. Some recent work has introduced dry electrode systems that do not
      require gel, but often introduce new problems such as comfort and signal quality.
      The principal goal of this study was to assess a new dry electrode BCI system in
      a very common task: spelling with a P300 BCI. A total of 23 subjects used a P300
      BCI to spell the word "LUCAS" while receiving real-time, closed-loop feedback.
      The dry system yielded classification accuracies that were similar to those
      obtained with gel systems. All subjects completed a questionnaire after data
      recording, and all subjects stated that the dry system was not uncomfortable.
      This is the first field validation of a dry electrode P300 BCI system, and paves
      the way for new research and development with EEG recording systems that are much
      more practical and convenient in field settings than conventional systems.

PMID- 22586363
TI  - What is the Thalamus in Zebrafish?
AB  - Current research on the thalamus and related structures in the zebrafish
      diencephalon identifies an increasing number of both neurological structures and
      ontogenetic processes as evolutionary conserved between teleosts and mammals. The
      patterning processes, for example, which during the embryonic development of
      zebrafish form the thalamus proper appear largely conserved. Yet also striking
      differences between zebrafish and other vertebrates have been observed,
      particularly when we look at mature and histologically differentiated brains. A
      case in point is the migrated preglomerular complex of zebrafish which evolved
      only within the lineage of ray-finned fish and has no counterpart in mammals or
      tetrapod vertebrates. Based on its function as a sensory relay station with
      projections to pallial zones, the preglomerular complex has been compared to
      specific thalamic nuclei in mammals. However, no thalamic projections to the
      zebrafish dorsal pallium, which corresponds topologically to the mammalian
      isocortex, have been identified. Merely one teleostean thalamic nucleus proper,
      the auditory nucleus, projects to a part of the dorsal telencephalon, the pallial
      amygdala. Studies on patterning mechanisms identify a rostral and caudal domain
      in the embryonic thalamus proper. In both, teleosts and mammals, the rostral
      domain gives rise to GABAergic neurons, whereas glutamatergic neurons originate
      in the caudal domain of the zebrafish thalamus. The distribution of GABAergic
      derivatives in the adult zebrafish brain, furthermore, revealed previously
      overlooked thalamic nuclei and redefined already established ones. These findings
      require some reconsideration regarding the topological origin of these adult
      structures. In what follows, I discuss how evolutionary conserved and newly
      acquired features of the developing and adult zebrafish thalamus can be compared
      to the mammalian situation.

PMID- 22586361
TI  - Crosstalk among Epigenetic Pathways Regulates Neurogenesis.
AB  - The process of neurogenesis includes neural stem cell proliferation, fate
      specification, young neuron migration, neuronal maturation, and functional
      integration into existing circuits. Although neurogenesis occurs largely during
      embryonic development, low levels but functionally important neurogenesis
      persists in restricted regions of the postnatal brain, including the subgranular
      zone of the dentate gyrus in the hippocampus and the subventricular zone of the
      lateral ventricles. This review will cover both embryonic and adult neurogenesis
      with an emphasis on the latter. Of the many endogenous mediators of postnatal
      neurogenesis, epigenetic pathways, such as mediators of DNA methylation,
      chromatin remodeling systems, and non-coding RNA modulators, appear to play an
      integral role. Mounting evidence shows that such epigenetic factors form
      regulatory networks, which govern each step of postnatal neurogenesis. In this
      review, we explore the emerging roles of epigenetic mechanisms particularly
      microRNAs, element-1 silencing transcription factor/neuron-restrictive silencing
      factor (REST/NRSF), polycomb proteins, and methyl-CpG bindings proteins, in
      regulating the entire process of postnatal and adult neurogenesis. We further
      summarize recent data regarding how the crosstalk among these different
      epigenetic proteins forms the critical regulatory network that regulates neuronal
      development. We finally discuss how crosstalk between these pathways may serve to
      translate environmental cues into control of the neurogenic process.

PMID- 22586364
TI  - Reaching movement onset- and end-related characteristics of EEG spectral power
      modulations.
AB  - The spectral power of intracranial field potentials shows movement-related
      modulations during reaching movements to different target positions that in
      frequencies up to the high-gamma range (approximately 50 to above 200 Hz) can be
      reliably used for single-trial inference of movement parameters. However,
      identifying spectral power modulations suitable for single-trial analysis for non
      invasive approaches remains a challenge. We recorded non-invasive
      electroencephalography (EEG) during a self-paced center-out and center-in arm
      movement task, resulting in eight reaching movement classes (four center-out,
      four center-in). We found distinct slow (<=5 Hz), MU (7.5-10 Hz), beta (12.5-25
      Hz), low-gamma (approximately 27.5-50 Hz), and high-gamma (above 50 Hz) movement
      onset- and end-related responses. Movement class-specific spectral power
      modulations were restricted to the beta band at approximately 1 s after movement
      end and could be explained by the sensitivity of this response to different
      static, post-movement electromyography (EMG) levels. Based on the beta band,
      significant single-trial inference of reaching movement endpoints was possible.
      The findings of the present study support the idea that single-trial decoding of
      different reaching movements from non-invasive EEG spectral power modulations is
      possible, but also suggest that the informative time window is after movement end
      and that the informative frequency range is restricted to the beta band.

PMID- 22586365
TI  - The role of neuronal calcium sensors in balancing synaptic plasticity and
      synaptic dysfunction.
AB  - Neuronal calcium sensors (NCS) readily bind calcium and undergo conformational
      changes enabling them to interact and regulate specific target molecules. These
      interactions lead to dynamic alterations in protein trafficking that
      significantly impact upon synaptic function. Emerging evidence suggests that NCS
      and alterations in Ca(2+) mobilization modulate glutamate receptor trafficking,
      subsequently determining the expression of different forms of synaptic
      plasticity. In this review, we aim to discuss the functional relevance of NCS in
      protein trafficking and their emerging role in synaptic plasticity. Their
      significance within the concept of "translational neuroscience" will also be
      highlighted, by assessing their potential as key molecules in neurodegeneration.

PMID- 22586366
TI  - Guidance of longitudinally projecting axons in the developing central nervous
      system.
AB  - The directed and stereotypical growth of axons to their synaptic targets is a
      crucial phase of neural circuit formation. Many axons in the developing
      vertebrate and invertebrate central nervous systems (CNSs), including those that
      remain on their own (ipsilateral), and those that cross over to the opposite
      (commissural), side of the midline project over long distances along the anterior
      posterior (A-P) body axis within precisely positioned longitudinally oriented
      tracts to facilitate the transmission of information between CNS regions. Despite
      the widespread distribution and functional importance of these longitudinal
      tracts, the mechanisms that regulate their formation and projection to poorly
      characterized synaptic targets remain largely unknown. Nevertheless, recent
      studies carried out in a variety of invertebrate and vertebrate model systems
      have begun to elucidate the molecular logic that controls longitudinal axon
      guidance.

PMID- 22586367
TI  - Molecular mechanisms of Cys-loop ion channel receptor modulation by ivermectin.
AB  - Ivermectin is an anthelmintic drug that works by inhibiting neuronal activity and
      muscular contractility in arthropods and nematodes. It works by activating
      glutamate-gated chloride channels (GluClRs) at nanomolar concentrations. These
      receptors, found exclusively in invertebrates, belong to the pentameric Cys-loop
      receptor family of ligand-gated ion channels (LGICs). Higher (micromolar)
      concentrations of ivermectin also activate or modulate vertebrate Cys-loop
      receptors, including the excitatory nicotinic and the inhibitory GABA type-A and
      glycine receptors (GlyRs). An X-ray crystal structure of ivermectin complexed
      with the C. elegans alpha GluClR demonstrated that ivermectin binds to the
      transmembrane domain in a cleft at the interface of adjacent subunits. It also
      identified three hydrogen bonds thought to attach ivermectin to its site. Site
      directed mutagenesis and voltage-clamp electrophysiology have also been employed
      to probe the binding site for ivermectin in alpha1 GlyRs. These have raised
      doubts as to whether the hydrogen bonds are essential for high ivermectin
      potency. Due to its lipophilic nature, it is likely that ivermectin accumulates
      in the membrane and binds reversibly (i.e., weakly) to its site. Several lines of
      evidence suggest that ivermectin opens the channel pore via a structural change
      distinct from that induced by the neurotransmitter agonist. Conformational
      changes occurring at locations distant from the pore can be probed using voltage
      clamp fluorometry (VCF), a technique which involves quantitating agonist-induced
      fluorescence changes from environmentally sensitive fluorophores covalently
      attached to receptor domains of interest. This technique has demonstrated that
      ivermectin induces a global conformational change that propagates from the
      transmembrane domain to the neurotransmitter binding site, thus suggesting a
      mechanism by which ivermectin potentiates neurotransmitter-gated currents.
      Together, this information provides new insights into the mechanisms of action of
      this important drug.

PMID- 22586369
TI  - Generation of neuromuscular specificity in Drosophila: novel mechanisms revealed
      by new technologies.
AB  - The Drosophila larval neuromuscular system is one of the best-characterized model
      systems for axon targeting. In each abdominal hemisegment, only 36 identified
      motor neurons form synaptic connections with just 30 target muscles in a highly
      specific and stereotypic manner. Studies in the 1990s identified several cell
      surface and secreted proteins that are expressed in specific muscles and
      contribute to target specificity. Emerging evidence suggests that target
      selection is determined not only by attraction to the target cells but also by
      exclusion from non-target cells. Proteins with leucine-rich repeats (LRR
      proteins) appear to be a major molecular family of proteins responsible for the
      targeting. While the demonstrated roles of the target-derived cues point to
      active recognition by presynaptic motor neurons, postsynaptic muscles also reach
      out and recognize specific motor neurons by sending out cellular protrusions
      called myopodia. Simultaneous live imaging of myopodia and growth cones has
      revealed that local and mutual recognition at the tip of myopodia is critical for
      selective synapse formation. A large number of candidate target cues have been
      identified on a single muscle, suggesting that target specificity is determined
      by the partially redundant and combinatorial function of multiple cues. Analyses
      of the seemingly simple neuromuscular system in Drosophila have revealed an
      unexpected complexity in the mechanisms of axon targeting.

PMID- 22586370
TI  - Significance of the dynamic expression of pax6 and dlx2 in the postnatal
      periventricular zone cells.

PMID- 22586368
TI  - Ca(2+) sensor proteins in dendritic spines: a race for Ca(2+).
AB  - Dendritic spines are believed to be micro-compartments of Ca(2+) regulation. In a
      recent study, it was suggested that the ubiquitous and evolutionarily conserved
      Ca(2+) sensor, calmodulin (CaM), is the first to intercept Ca(2+) entering the
      spine and might be responsible for the fast decay of Ca(2+) transients in spines.
      Neuronal calcium sensor (NCS) and neuronal calcium-binding protein (nCaBP)
      families consist of Ca(2+) sensors with largely unknown synaptic functions
      despite an increasing number of interaction partners. Particularly how these
      sensors operate in spines in the presence of CaM has not been discussed in detail
      before. The limited Ca(2+) resources and the existence of common targets create a
      highly competitive environment where Ca(2+) sensors compete with each other for
      Ca(2+) and target binding. In this review, we take a simple numerical approach to
      put forth possible scenarios and their impact on signaling via Ca(2+) sensors of
      the NCS and nCaBP families. We also discuss the ways in which spine geometry and
      properties of ion channels, their kinetics and distribution, alter the spatio
      temporal aspects of Ca(2+) transients in dendritic spines, whose interplay with
      Ca(2+) sensors in turn influences the race for Ca(2+).

PMID- 22586371
TI  - Stimulus intensity-dependent modulations of hippocampal long-term potentiation by
      basolateral amygdala priming.
AB  - There is growing realization that the relationship between memory and
      stress/emotionality is complicated, and may include both memory enhancing and
      memory impairing aspects. It has been suggested that the underlying mechanisms
      involve amygdala modulation of hippocampal synaptic plasticity, such as long-term
      potentiation (LTP). We recently reported that while in CA1 basolateral amygdala
      (BLA) priming impaired theta stimulation induced LTP, it enhanced LTP in the
      dentate gyrus (DG). However, emotional and stressfull experiences were found to
      activate synaptic plasticity within the BLA, raising the possibility that BLA
      modulation of other brain regions may be altered as well, as it may depend on the
      way the BLA is activated or is responding. In previous studies BLA priming
      stimulation was relatively weak (1 V, 50 MUs pulse duration). In the present
      study we assessed the effects of two stronger levels of BLA priming stimulation
      (1 V or 2 V, 100 MUs pulse duration) on LTP induction in hippocampal DG and CA1,
      in anesthetized rats. Results show that 1V-BLA priming stimulation enhanced but
      2V-BLA priming stimulation impaired DG LTP; however, both levels of BLA priming
      stimulation impaired CA1 LTP, suggesting that modulation of hippocampal synaptic
      plasticity by amygdala is dependent on the degree of amygdala activation. These
      findings suggest that plasticity-induced within the amygdala, by stressful
      experiences induces a form of metaplasticity that would alter the way the
      amygdala may modulate memory-related processes in other brain areas, such as the
      hippocampus.

PMID- 22586373
TI  - Retinal Mosaics: Pattern Formation Driven by Local Interactions between Homotypic
      Neighbors.

PMID- 22586372
TI  - Divisive normalization and neuronal oscillations in a single hierarchical
      framework of selective visual attention.
AB  - Divisive normalization models of covert attention commonly use spike rate
      modulations as indicators of the effect of top-down attention. In addition, an
      increasing number of studies have shown that top-down attention increases the
      synchronization of neuronal oscillations as well, particularly in gamma-band
      frequencies (25-100 Hz). Although modulations of spike rate and synchronous
      oscillations are not mutually exclusive as mechanisms of attention, there has
      thus far been little effort to integrate these concepts into a single framework
      of attention. Here, we aim to provide such a unified framework by expanding the
      normalization model of attention with a multi-level hierarchical structure and a
      time dimension; allowing the simulation of a recently reported backward
      progression of attentional effects along the visual cortical hierarchy. A simple
      cascade of normalization models simulating different cortical areas is shown to
      cause signal degradation and a loss of stimulus discriminability over time. To
      negate this degradation and ensure stable neuronal stimulus representations, we
      incorporate a kind of oscillatory phase entrainment into our model that has
      previously been proposed as the "communication-through-coherence" (CTC)
      hypothesis. Our analysis shows that divisive normalization and oscillation models
      can complement each other in a unified account of the neural mechanisms of
      selective visual attention. The resulting hierarchical normalization and
      oscillation (HNO) model reproduces several additional spatial and temporal
      aspects of attentional modulation and predicts a latency effect on neuronal
      responses as a result of cued attention.

PMID- 22586374
TI  - Dynamic temporal signal processing in the inferior colliculus of echolocating
      bats.
AB  - In nature, communication sounds among animal species including humans are typical
      complex sounds that occur in sequence and vary with time in several parameters
      including amplitude, frequency, duration as well as separation, and order of
      individual sounds. Among these multiple parameters, sound duration is a simple
      but important one that contributes to the distinct spectral and temporal
      attributes of individual biological sounds. Likewise, the separation of
      individual sounds is an important temporal attribute that determines an animal's
      ability in distinguishing individual sounds. Whereas duration selectivity of
      auditory neurons underlies an animal's ability in recognition of sound duration,
      the recovery cycle of auditory neurons determines a neuron's ability in
      responding to closely spaced sound pulses and therefore, it underlies the
      animal's ability in analyzing the order of individual sounds. Since the multiple
      parameters of naturally occurring communication sounds vary with time, the
      analysis of a specific sound parameter by an animal would be inevitably affected
      by other co-varying sound parameters. This is particularly obvious in
      insectivorous bats, which rely on analysis of returning echoes for prey capture
      when they systematically vary the multiple pulse parameters throughout a target
      approach sequence. In this review article, we present our studies of dynamic
      variation of duration selectivity and recovery cycle of neurons in the central
      nucleus of the inferior colliculus of the frequency-modulated bats to highlight
      the dynamic temporal signal processing of central auditory neurons. These studies
      use single pulses and three biologically relevant pulse-echo (P-E) pairs with
      varied duration, gap, and amplitude difference similar to that occurring during
      search, approach, and terminal phases of hunting by bats. These studies show that
      most collicular neurons respond maximally to a best tuned sound duration (BD).
      The sound duration to which these neurons are tuned correspond closely to the
      behaviorally relevant sounds occurring at different phases of hunting. The
      duration selectivity of these collicular neurons progressively increases with
      decrease in the duration of pulse and echo, P-E gap, and P-E amplitude
      difference. GABAergic inhibition plays an important role in shaping the duration
      selectivity of these collicular neurons. The duration selectivity of these
      neurons is systematically organized along the tonotopic axis of the inferior
      colliculus and is closely correlated with the graded spatial distribution of
      GABA(A) receptors. Duration-selective collicular neurons have a wide range of
      recovery cycle covering the P-E intervals occurring throughout the entire target
      approaching sequences. Collicular neurons with low best frequency and short BD
      recover rapidly when stimulated with P-E pairs with short duration and small P-E
      amplitude difference, whereas neurons with high best frequency and long BD
      recover rapidly when stimulated with P-E pairs with long duration and large P-E
      amplitude difference. This dynamic variation of echo duration selectivity and
      recovery cycle of collicular neurons may serve as the neural basis underlying
      successful hunting by bats. Conceivably, high best frequency neurons with long BD
      would be suitable for echo recognition during search and approach phases of
      hunting when the returning echoes are high in frequency, large in P-E amplitude
      difference, long in duration but low in repetition rate. Conversely, low best
      frequency neurons with shorter BD and sharper duration selectivity would be
      suitable for echo recognition during the terminal phase of hunting when the
      highly repetitive echoes are low in frequency, small in P-E amplitude difference,
      and short in duration. Furthermore, the tonotopically organized duration
      selectivity would make it possible to facilitate the recruitment of different
      groups of collicular neurons along the tonotopic axis for effective processing of
      the returning echoes throughout the entire course of hunting.

PMID- 22586375
TI  - The auditory and non-auditory brain areas involved in tinnitus. An emergent
      property of multiple parallel overlapping subnetworks.
AB  - Tinnitus is the perception of a sound in the absence of an external sound source.
      It is characterized by sensory components such as the perceived loudness, the
      lateralization, the tinnitus type (pure tone, noise-like) and associated
      emotional components, such as distress and mood changes. Source localization of
      quantitative electroencephalography (qEEG) data demonstrate the involvement of
      auditory brain areas as well as several non-auditory brain areas such as the
      anterior cingulate cortex (dorsal and subgenual), auditory cortex (primary and
      secondary), dorsal lateral prefrontal cortex, insula, supplementary motor area,
      orbitofrontal cortex (including the inferior frontal gyrus), parahippocampus,
      posterior cingulate cortex and the precuneus, in different aspects of tinnitus.
      Explaining these non-auditory brain areas as constituents of separable
      subnetworks, each reflecting a specific aspect of the tinnitus percept increases
      the explanatory power of the non-auditory brain areas involvement in tinnitus.
      Thus, the unified percept of tinnitus can be considered an emergent property of
      multiple parallel dynamically changing and partially overlapping subnetworks,
      each with a specific spontaneous oscillatory pattern and functional connectivity
      signature.

PMID- 22586376
TI  - Histamine neurons in the tuberomamillary nucleus: a whole center or distinct
      subpopulations?
AB  - Histamine axons originate from a single source, the tuberomamillary nucleus (TMN)
      of the posterior hypothalamus, to innervate almost all central nervous system
      (CNS) regions. This feature, a compact cell group with widely distributed fibers,
      resembles that of other amine systems, such as noradrenaline or serotonin, and is
      consistent with a function for histamine over a host of physiological processes,
      including the regulation of the sleep-wake cycle, appetite, endocrine
      homeostasis, body temperature, pain perception, learning, memory, and emotion. An
      important question is whether these diverse physiological roles are served by
      different histamine neuronal subpopulation. While the histamine system is
      generally regarded as one single functional unit that provides histamine
      throughout the brain, evidence is beginning to accumulate in favor of
      heterogeneity of histamine neurons. The aim of this review is to summarize
      experimental evidence demonstrating that histamine neurons are heterogeneous,
      organized into functionally distinct circuits, impinging on different brain
      regions, and displaying selective control mechanisms. This could imply
      independent functions of subsets of histamine neurons according to their
      respective origin and terminal projections.

PMID- 22586377
TI  - Computational models of neurophysiological correlates of tinnitus.
AB  - The understanding of tinnitus has progressed considerably in the past decade, but
      the details of the mechanisms that give rise to this phantom perception of sound
      without a corresponding acoustic stimulus have not yet been pinpointed. It is now
      clear that tinnitus is generated in the brain, not in the ear, and that it is
      correlated with pathologically altered spontaneous activity of neurons in the
      central auditory system. Both increased spontaneous firing rates and increased
      neuronal synchrony have been identified as putative neuronal correlates of
      phantom sounds in animal models, and both phenomena can be triggered by damage to
      the cochlea. Various mechanisms could underlie the generation of such aberrant
      activity. At the cellular level, decreased synaptic inhibition and increased
      neuronal excitability, which may be related to homeostatic plasticity, could lead
      to an over-amplification of natural spontaneous activity. At the network level,
      lateral inhibition could amplify differences in spontaneous activity, and
      structural changes such as reorganization of tonotopic maps could lead to self
      sustained activity in recurrently connected neurons. However, it is difficult to
      disentangle the contributions of different mechanisms in experiments, especially
      since not all changes observed in animal models of tinnitus are necessarily
      related to tinnitus. Computational modeling presents an opportunity of evaluating
      these mechanisms and their relation to tinnitus. Here we review the computational
      models for the generation of neurophysiological correlates of tinnitus that have
      been proposed so far, and evaluate predictions and compare them to available
      data. We also assess the limits of their explanatory power, thus demonstrating
      where an understanding is still lacking and where further research may be needed.
      Identifying appropriate models is important for finding therapies, and we
      therefore, also summarize the implications of the models for approaches to treat
      tinnitus.

PMID- 22586378
TI  - Imaging the neural correlates of tinnitus: a comparison between animal models and
      human studies.
AB  - Tinnitus is the perception of a sound, a so-called "phantom sound," in the
      absence of a physical sound. The phantom perception persists after transection of
      the auditory nerve, indicating that the site of tinnitus manifestation is in the
      central nervous system. Imaging studies in tinnitus sufferers have revealed
      increased neuronal activity-hyperactivity-in subcortical and cortical auditory
      centers. These studies have demonstrated that non-auditory brain areas, such as
      the limbic system, are involved in the neural basis of tinnitus, Finally human
      imaging studies have led to novel hypotheses for the generation of tinnitus, such
      as the thalamocortical dysrhythmia hypothesis. Imaging in animal models of
      tinnitus exhibit similarities to results from human studies and have revealed
      hyperexcitability of auditory brain centers as a neural correlate of tinnitus. We
      propose that the comparison between animal model and human studies will aid in
      the design of appropriate experimental paradigms aimed at elucidating the
      cellular and circuit mechanisms underlying tinnitus.

PMID- 22586379
TI  - Reinstatement of extinguished fear by an unextinguished conditional stimulus.
AB  - Anxiety disorders are often treated using extinction-based exposure therapy, but
      relapse is common and can occur as a result of reinstatement, whereby an aversive
      "trigger" can reinstate extinguished fear. Animal models of reinstatement
      commonly utilize a Pavlovian fear conditioning procedure, in which subjects are
      first trained to fear a conditional stimulus (CS) by pairing it with an aversive
      unconditional stimulus (US), and then extinguished by repeated presentations of
      the CS alone. Reinstatement is typically induced by exposing subjects to an
      aversive US after extinction, but here we show that exposure to a non
      extinguished CS can reinstate conditional fear responding to an extinguished CS,
      a phenomenon we refer to as "conditional reinstatement" (CRI). Rats were trained
      to fear two CSs (light and tone) and subsequently underwent extinction training
      to only one CS (counterbalanced). Presenting the unextinguished CS (but not a
      novel cue) immediately after extinction reinstated conditional fear responding to
      the extinguished CS in a test session given 24 h later. These findings indicate
      that reinstatement of extinguished fear can be triggered by exposure to
      conditional as well as unconditional aversive stimuli, and this may help to
      explain why relapse is common following clinical extinction therapy in humans.
      Further study of CRI using animal models may prove useful for developing refined
      extinction therapies that are more resistant to reinstatement.

PMID- 22586381
TI  - How do we think machines think? An fMRI study of alleged competition with an
      artificial intelligence.
AB  - Mentalizing is defined as the inference of mental states of fellow humans, and is
      a particularly important skill for social interactions. Here we assessed whether
      activity in brain areas involved in mentalizing is specific to the processing of
      mental states or can be generalized to the inference of non-mental states by
      comparing brain responses during the interaction with an intentional and an
      artificial agent. Participants were scanned using fMRI during interactive rock
      paper-scissors games while believing their opponent was a fellow human
      (Intentional agent, Int), a humanoid robot endowed with an artificial
      intelligence (Artificial agent, Art), or a computer playing randomly (Random
      agent, Rnd). Participants' subjective reports indicated that they adopted
      different stances against the three agents. The contrast of brain activity during
      interaction with the artificial and the random agents didn't yield any cluster at
      the threshold used, suggesting the absence of a reproducible stance when
      interacting with an artificial intelligence. We probed response to the artificial
      agent in regions of interest corresponding to clusters found in the contrast
      between the intentional and the random agents. In the precuneus involved in
      working memory, the posterior intraparietal suclus, in the control of attention
      and the dorsolateral prefrontal cortex, in executive functions, brain activity
      for Art was larger than for Rnd but lower than for Int, supporting the
      intrinsically engaging nature of social interactions. A similar pattern in the
      left premotor cortex and anterior intraparietal sulcus involved in motor
      resonance suggested that participants simulated human, and to a lesser extend
      humanoid robot actions, when playing the game. Finally, mentalizing regions, the
      medial prefrontal cortex and right temporoparietal junction, responded to the
      human only, supporting the specificity of mentalizing areas for interactions with
      intentional agents.

PMID- 22586380
TI  - Adult mouse basal forebrain harbors two distinct cholinergic populations defined
      by their electrophysiology.
AB  - We performed whole-cell recordings from basal forebrain (BF) cholinergic neurons
      in transgenic mice expressing enhanced green fluorescent protein (eGFP) under the
      control of the choline acetyltransferase promoter. BF cholinergic neurons can be
      differentiated into two electrophysiologically identifiable subtypes: early and
      late firing neurons. Early firing neurons (~70%) are more excitable, show
      prominent spike frequency adaptation and are more susceptible to depolarization
      blockade, a phenomenon characterized by complete silencing of the neuron
      following initial action potentials. Late firing neurons (~30%), albeit being
      less excitable, could maintain a tonic discharge at low frequencies. In voltage
      clamp analysis, we have shown that early firing neurons have a higher density of
      low voltage activated (LVA) calcium currents. These two cholinergic cell
      populations might be involved in distinct functions: the early firing group being
      more suitable for phasic changes in cortical acetylcholine release associated
      with attention while the late firing neurons could support general arousal by
      maintaining tonic acetylcholine levels.

PMID- 22586382
TI  - When planning results in loss of control: intention-based reflexivity and working
      memory.
AB  - In this review, the authors discuss the seemingly paradoxical loss of control
      associated with states of high readiness to execute a plan, termed "intention
      based reflexivity." The review suggests that the neuro-cognitive systems involved
      in the preparation of novel plans are different than those involved in
      preparation of practiced plans (i.e., those that have been executed beforehand).
      When the plans are practiced, intention-based reflexivity depends on the prior
      availability of response codes in long-term memory (LTM). When the plans are
      novel, reflexivity is observed when the plan is pending and the goal has not yet
      been achieved. Intention-based reflexivity also depends on the availability of
      working-memory (WM) limited resources and the motivation to prepare. Reflexivity
      is probably related to the fact that, unlike reactive control (once a plan is
      prepared), proactive control tends to be relatively rigid.

PMID- 22586383
TI  - A combination of thematic and similarity-based semantic processes confers
      resistance to deficit following left hemisphere stroke.
AB  - Semantic knowledge may be organized in terms of similarity relations based on
      shared features and/or complementary relations based on co-occurrence in events.
      Thus, relationships between manipulable objects such as tools may be defined by
      their functional properties (what the objects are used for) or thematic
      properties (e.g., what the objects are used with or on). A recent study from our
      laboratory used eye-tracking to examine incidental activation of semantic
      relations in a word-picture matching task and found relatively early activation
      of thematic relations (e.g., broom-dustpan), later activation of general
      functional relations (e.g., broom-sponge), and an intermediate pattern for
      specific functional relations (e.g., broom-vacuum cleaner). Combined with other
      recent studies, these results suggest that there are distinct semantic systems
      for thematic and similarity-based knowledge and that the "specific function"
      condition drew on both systems. This predicts that left hemisphere stroke that
      damages either system (but not both) may spare specific function processing. The
      present experiment tested these hypotheses using the same experimental paradigm
      with participants with left hemisphere lesions (N = 17). The results revealed
      that, compared to neurologically intact controls (N = 12), stroke participants
      showed later activation of thematic and general function relations, but
      activation of specific function relations was spared and was significantly
      earlier for stroke participants than controls. Across the stroke participants,
      activation of thematic and general function relations was negatively correlated,
      further suggesting that damage tended to affect either one semantic system or the
      other. These results support the distinction between similarity-based and
      complementarity-based semantic relations and suggest that relations that draw on
      both systems are relatively more robust to damage.

PMID- 22586384
TI  - Brain networks of visuospatial attention and their disruption in visual neglect.
AB  - Visual neglect is a multi-component syndrome including prominent attentional
      disorders. Research on the functional mechanisms of neglect is now moving from
      the description of dissociations in patients' performance to the identification
      of the possible component deficits and of their interaction with compensatory
      strategies. In recent years, the dissection of attentional deficits in neglect
      has progressed in parallel with increasing comprehension of the anatomy and
      function of large-scale brain networks implicated in attentional processes. This
      review focuses on the anatomy and putative functions of attentional circuits in
      the brain, mainly subserved by fronto-parietal networks, with a peculiar although
      not yet completely elucidated role for the right hemisphere. Recent results are
      discussed concerning the influence of a non-spatial attentional function, phasic
      alertness, on conscious perception in normal participants and on conflict
      resolution in neglect patients. The rapid rate of expansion of our knowledge of
      these systems raises hopes for the development of effective strategies to improve
      the functioning of the attentional networks in brain-damaged patients.

PMID- 22586385
TI  - The social environment and neurogenesis in the adult Mammalian brain.
AB  - Adult neurogenesis - the formation of new neurons in adulthood - has been shown
      to be modulated by a variety of endogenous (e.g., trophic factors,
      neurotransmitters, and hormones) as well as exogenous (e.g., physical activity
      and environmental complexity) factors. Research on exogenous regulators of adult
      neurogenesis has focused primarily on the non-social environment. More recently,
      however, evidence has emerged suggesting that the social environment can also
      affect adult neurogenesis. The present review details the effects of adult-adult
      (e.g., mating and chemosensory interactions) and adult-offspring (e.g.,
      gestation, parenthood, and exposure to offspring) interactions on adult
      neurogenesis. In addition, the effects of a stressful social environment (e.g.,
      lack of social support and dominant-subordinate interactions) on adult
      neurogenesis are reviewed. The underlying hormonal mechanisms and potential
      functional significance of adult-generated neurons in mediating social behaviors
      are also discussed.

PMID- 22586387
TI  - Eye contact with neutral and smiling faces: effects on autonomic responses and
      frontal EEG asymmetry.
AB  - In our previous studies we have shown that seeing another person "live" with a
      direct vs. averted gaze results in enhanced skin conductance responses (SCRs)
      indicating autonomic arousal and in greater relative left-sided frontal activity
      in the electroencephalography (asymmetry in the alpha-band power), associated
      with approach motivation. In our studies, however, the stimulus persons had a
      neutral expression. In real-life social interaction, eye contact is often
      associated with a smile, which is another signal of the sender's approach-related
      motivation. A smile could, therefore, enhance the affective-motivational
      responses to eye contact. In the present study, we investigated whether the
      facial expression (neutral vs. social smile) would modulate autonomic arousal and
      frontal EEG alpha-band asymmetry to seeing a direct vs. an averted gaze in faces
      presented "live" through a liquid crystal (LC) shutter. The results showed that
      the SCRs were greater for the direct than the averted gaze and that the effect of
      gaze direction was more pronounced for a smiling than a neutral face. However, in
      this study, gaze direction and facial expression did not affect the frontal EEG
      asymmetry, although, for gaze direction, we found a marginally significant
      correlation between the degree of an overall bias for asymmetric frontal activity
      and the degree to which direct gaze elicited stronger left-sided frontal activity
      than did averted gaze.

PMID- 22586388
TI  - Neuroimaging evidence for social rank theory.

PMID- 22586389
TI  - Iconic memory requires attention.
AB  - Two experiments investigated whether attention plays a role in iconic memory,
      employing either a change detection paradigm (Experiment 1) or a partial-report
      paradigm (Experiment 2). In each experiment, attention was taxed during initial
      display presentation, focusing the manipulation on consolidation of information
      into iconic memory, prior to transfer into working memory. Observers were able to
      maintain high levels of performance (accuracy of change detection or
      categorization) even when concurrently performing an easy visual search task (low
      load). However, when the concurrent search was made difficult (high load),
      observers' performance dropped to almost chance levels, while search accuracy
      held at single-task levels. The effects of attentional load remained the same
      across paradigms. The results suggest that, without attention, participants
      consolidate in iconic memory only gross representations of the visual scene,
      information too impoverished for successful detection of perceptual change or
      categorization of features.

PMID- 22586386
TI  - The role of consciousness in cognitive control and decision making.
AB  - Here we review studies on the complexity and strength of unconscious information
      processing. We focus on empirical evidence that relates awareness of information
      to cognitive control processes (e.g., response inhibition, conflict resolution,
      and task-switching), the life-time of information maintenance (e.g., working
      memory) and the possibility to integrate multiple pieces of information across
      space and time. Overall, the results that we review paint a picture of local and
      specific effects of unconscious information on various (high-level) brain
      regions, including areas in the prefrontal cortex. Although this neural
      activation does not elicit any conscious experience, it is functional and capable
      of influencing many perceptual, cognitive (control) and decision-related
      processes, sometimes even for relatively long periods of time. However, recent
      evidence also points out interesting dissociations between conscious and
      unconscious information processing when it comes to the duration, flexibility and
      the strategic use of that information for complex operations and decision-making.
      Based on the available evidence, we conclude that the role of task-relevance of
      subliminal information and meta-cognitive factors in unconscious cognition need
      more attention in future work.

PMID- 22586390
TI  - Modulations of ongoing alpha oscillations predict successful short-term visual
      memory encoding.
AB  - Alpha-frequency band oscillations have been shown to be one of the most prominent
      aspects of neuronal ongoing oscillatory activity, as reflected by
      electroencephalography (EEG) recordings. First thought to reflect an idling
      state, a recent framework indicates that alpha power reflects cortical
      inhibition. In the present study, the role of oscillations in the upper alpha
      band (12 Hz) was investigated during a change-detection test of short-term visual
      memory. If alpha oscillations arise from a purely inhibitory process, higher
      alpha power before sample stimulus presentation would be expected to correlate
      with poorer performance. Instead, participants with faster reaction-times showed
      stronger alpha power before the sample stimulus in frontal and posterior regions.
      Additionally, faster participants showed stronger alpha desynchronization after
      the stimulus in a group of right frontal and left posterior electrodes. The same
      pattern of electrodes showed stronger alpha with higher working-memory load, so
      that when more items were processed, alpha power desynchronized faster after the
      stimulus. During memory maintenance, alpha power was greater when more items were
      held in memory, likely due to a faster resynchronization. These data are
      consistent with the hypothesis that the level of suppression of alpha power by
      stimulus presentation is an important factor for successfully encoding visual
      stimuli. The data are also consistent with a role for alpha as actively
      participating in attentional processes.

PMID- 22586391
TI  - Population coding in sparsely connected networks of noisy neurons.
AB  - This study examines the relationship between population coding and spatial
      connection statistics in networks of noisy neurons. Encoding of sensory
      information in the neocortex is thought to require coordinated neural
      populations, because individual cortical neurons respond to a wide range of
      stimuli, and exhibit highly variable spiking in response to repeated stimuli.
      Population coding is rooted in network structure, because cortical neurons
      receive information only from other neurons, and because the information they
      encode must be decoded by other neurons, if it is to affect behavior. However,
      population coding theory has often ignored network structure, or assumed
      discrete, fully connected populations (in contrast with the sparsely connected,
      continuous sheet of the cortex). In this study, we modeled a sheet of cortical
      neurons with sparse, primarily local connections, and found that a network with
      this structure could encode multiple internal state variables with high signal-to
      noise ratio. However, we were unable to create high-fidelity networks by
      instantiating connections at random according to spatial connection
      probabilities. In our models, high-fidelity networks required additional
      structure, with higher cluster factors and correlations between the inputs to
      nearby neurons.

PMID- 22586392
TI  - Recurrent coupling improves discrimination of temporal spike patterns.
AB  - Despite the ubiquitous presence of recurrent synaptic connections in sensory
      neuronal systems, their general functional purpose is not well understood. A
      recent conceptual advance has been achieved by theories of reservoir computing in
      which recurrent networks have been proposed to generate short-term memory as well
      as to improve neuronal representation of the sensory input for subsequent
      computations. Here, we present a numerical study on the distinct effects of
      inhibitory and excitatory recurrence in a canonical linear classification task.
      It is found that both types of coupling improve the ability to discriminate
      temporal spike patterns as compared to a purely feed-forward system, although in
      different ways. For a large class of inhibitory networks, the network's
      performance is optimal as long as a fraction of roughly 50% of neurons per
      stimulus is active in the resulting population code. Thereby the contribution of
      inactive neurons to the neural code is found to be even more informative than
      that of the active neurons, generating an inherent robustness of classification
      performance against temporal jitter of the input spikes. Excitatory couplings are
      found to not only produce a short-term memory buffer but also to improve linear
      separability of the population patterns by evoking more irregular firing as
      compared to the purely inhibitory case. As the excitatory connectivity becomes
      more sparse, firing becomes more variable, and pattern separability improves. We
      argue that the proposed paradigm is particularly well-suited as a conceptual
      framework for processing of sensory information in the auditory pathway.

PMID- 22586393
TI  - Electronic data capture, representation, and applications for neuroimaging.

PMID- 22586394
TI  - PEDOT-CNT Composite Microelectrodes for Recording and Electrostimulation
      Applications: Fabrication, Morphology, and Electrical Properties.
AB  - Composites of carbon nanotubes and poly(3,4-ethylenedioxythiophene, PEDOT) and
      layers of PEDOT are deposited onto microelectrodes by electropolymerization of
      ethylenedioxythiophene in the presence of a suspension of carbon nanotubes and
      polystyrene sulfonate. Analysis by FIB and SEM demonstrates that CNT-PEDOT
      composites exhibit a porous morphology whereas PEDOT layers are more compact.
      Accordingly, capacitance and charge injection capacity of the composite material
      exceed those of pure PEDOT layers. In vitro cell culture experiments reveal
      excellent biocompatibility and adhesion of both PEDOT and PEDOT-CNT electrodes.
      Signals recorded from heart muscle cells demonstrate the high S/N ratio
      achievable with these electrodes. Long-term pulsing experiments confirm stability
      of charge injection capacity. In conclusion, a robust fabrication procedure for
      composite PEDOT-CNT electrodes is demonstrated and results show that these
      electrodes are well suited for stimulation and recording in cardiac and
      neurophysiological research.

PMID- 22586395
TI  - Heme cytotoxicity and the pathogenesis of immune-mediated inflammatory diseases.
AB  - Heme, iron (Fe) protoporphyrin IX, functions as a prosthetic group in a range of
      hemoproteins essential to support life under aerobic conditions. The Fe contained
      within the prosthetic heme groups of these hemoproteins can catalyze the
      production of reactive oxygen species. Presumably for this reason, heme must be
      sequestered within those hemoproteins, thereby shielding the reactivity of its Fe
      heme. However, under pathologic conditions associated with oxidative stress, some
      hemoproteins can release their prosthetic heme groups. While this heme is not
      necessarily damaging per se, it becomes highly cytotoxic in the presence of a
      range of inflammatory mediators such as tumor necrosis factor. This can lead to
      tissue damage and, as such, exacerbate the pathologic outcome of several immune
      mediated inflammatory conditions. Presumably, targeting "free heme" may be used
      as a therapeutic intervention against these diseases.

PMID- 22586397
TI  - Voltage-dependent gating of HERG potassium channels.
AB  - The mechanisms by which voltage-gated channels sense changes in membrane voltage
      and energetically couple this with opening of the ion conducting pore has been
      the source of significant interest. In voltage-gated potassium (Kv) channels,
      much of our knowledge in this area comes from Shaker-type channels, for which
      voltage-dependent gating is quite rapid. In these channels, activation and
      deactivation are associated with rapid reconfiguration of the voltage-sensing
      domain unit that is electromechanically coupled, via the S4-S5 linker helix, to
      the rate-limiting opening of an intracellular pore gate. However, fast voltage
      dependent gating kinetics are not typical of all Kv channels, such as Kv11.1
      (human ether-a-go-go related gene, hERG), which activates and deactivates very
      slowly. Compared to Shaker channels, our understanding of the mechanisms
      underlying slow hERG gating is much poorer. Here, we present a comparative review
      of the structure-function relationships underlying activation and deactivation
      gating in Shaker and hERG channels, with a focus on the roles of the voltage
      sensing domain and the S4-S5 linker that couples voltage sensor movements to the
      pore. Measurements of gating current kinetics and fluorimetric analysis of
      voltage sensor movement are consistent with models suggesting that the hERG
      activation pathway contains a voltage independent step, which limits voltage
      sensor transitions. Constraints upon hERG voltage sensor movement may result from
      loose packing of the S4 helices and additional intra-voltage sensor counter
      charge interactions. More recent data suggest that key amino acid differences in
      the hERG voltage-sensing unit and S4-S5 linker, relative to fast activating
      Shaker-type Kv channels, may also contribute to the increased stability of the
      resting state of the voltage sensor.

PMID- 22586396
TI  - Heme oxygenase, inflammation, and fibrosis: the good, the bad, and the ugly?
AB  - Upon injury, prolonged inflammation and oxidative stress may cause pathological
      wound healing and fibrosis, leading to formation of excessive scar tissue.
      Fibrogenesis can occur in most organs and tissues and may ultimately lead to
      organ dysfunction and failure. The underlying mechanisms of pathological wound
      healing still remain unclear, and are considered to be multifactorial, but so
      far, no efficient anti-fibrotic therapies exist. Extra- and intracellular levels
      of free heme may be increased in a variety of pathological conditions due to
      release from hemoproteins. Free heme possesses pro-inflammatory and oxidative
      properties, and may act as a danger signal. Effects of free heme may be
      counteracted by heme-binding proteins or by heme degradation. Heme is degraded by
      heme oxygenase (HO) that exists as two isoforms: inducible HO-1 and
      constitutively expressed HO-2. HO generates the effector molecules
      biliverdin/bilirubin, carbon monoxide, and free iron/ferritin. HO deficiency in
      mouse and man leads to exaggerated inflammation following mild insults, and
      accumulating epidemiological and preclinical studies support the widely
      recognized notion of the cytoprotective, anti-oxidative, and anti-inflammatory
      effects of the activity of the HO system and its effector molecules. In this
      review, we address the potential effects of targeted HO-1 induction or
      administration of HO-effector molecules as therapeutic targets in fibrotic
      conditions to counteract inflammatory and oxidative insults. This is exemplified
      by various clinically relevant conditions, such as hypertrophic scarring, chronic
      inflammatory liver disease, chronic pancreatitis, and chronic graft rejection in
      transplantation.

PMID- 22586399
TI  - Development of a rapid and confirmatory method to identify ganoderic acids in
      ganoderma mushrooms.
AB  - To examine the composition of lanostanoids in Ganoderma lucidum, we have
      developed a liquid chromatography-mass spectrometry (LC-MS) method by using the
      ganoderic acids isolated in our laboratory as reference standards. The identity
      of 14 peaks in the high performance liquid chromatogram (HPLC) of G. lucidum has
      been confirmed. By using the HPLC retention times of these ganoderic acids and
      their mass fragmentation patterns established in this paper, one can use LC-MS to
      analyze G. lucidum without requiring the reference standards of these 14
      ganoderic acids. Subsequently, only the HPLC-UV method would be needed to analyze
      routine samples of G. lucidum.

PMID- 22586398
TI  - mGlu5 Receptor Functional Interactions and Addiction.
AB  - The idea of "receptor mosaics" is that proteins may form complex and dynamic
      networks with respect to time and composition. These have the potential to
      markedly expand the diversity and specificity of G protein-coupled receptors
      (GPCR) signaling, particularly in neural cells, where a few key receptors have
      been implicated in many neurological and psychiatric disorders, including
      addiction. Metabotropic glutamate type 5 receptors (mGlu5) can form complexes
      with other GPCRs, including adenosine A(2A) and dopamine D(2) receptors. mGlu5
      containing complexes have been reported in the striatum, a brain region critical
      for mediating the rewarding and incentive motivational properties of drugs of
      abuse. mGlu5-containing complexes and/or downstream interactions between
      divergent receptors may play roles in addiction-relevant behaviors. Interactions
      between mGlu5 receptors and other GPCRs can regulate the rewarding and
      conditioned effects of drugs as well as drug-seeking behaviors. mGlu5 complexes
      may influence striatal function, including GABAergic output of striatopallidal
      neurons and glutamatergic input from corticostriatal afferents. Given their
      discrete localization, mGlu5-[non-mGlu5] receptor interactions and/or mGlu5
      containing complexes may minimize off-target effects and thus provide a novel
      avenue for drug discovery. The therapeutic targeting of receptor-receptor
      functional interactions and/or receptor mosaics in a tissue specific or temporal
      manner (for example, a sub-population of receptors in a "pathological state")
      might reduce detrimental side effects that may otherwise impair vital brain
      functions.

PMID- 22586400
TI  - Ion channel screening: advances in technologies and analysis.

PMID- 22586401
TI  - Arterial-ventricular coupling with aging and disease.
AB  - Age is the dominant risk factor for cardiovascular diseases. Understanding the
      coupling between the left ventricle (LV) and arterial system, termed arterial
      ventricular coupling (E(A)/E(LV)), provides important mechanistic insights into
      the complex cardiovascular system and its changes with aging in the absence and
      presence of disease. E(A)/E(LV) can be indexed by the ratio of effective arterial
      elastance (E(A); a measure of the net arterial load exerted on the LV) to left
      ventricular end-systolic elastance (E(LV); a load-independent measure of left
      ventricular chamber performance). Age-associated alterations in arterial
      structure and function, including diameter, wall thickness, wall stiffness, and
      endothelial dysfunction, contribute to a gradual increase in resting E(A) with
      age. Remarkably there is a corresponding increase in resting E(LV) with age, due
      to alterations to LV remodeling (loss in myocyte number, increased collagen) and
      function. These age-adaptations at rest likely occur, at least, in response to
      the age-associated increase in E(A) and ensure that E(A)/E(LV) is closely
      maintained within a narrow range, allowing for optimal energetic efficiency at
      the expense of mechanical efficacy. This optimal coupling at rest is also
      maintained when aging is accompanied by the presence of hypertension, and
      obesity, despite further increases in E(A) and E(LV) in these conditions. In
      contrast, in heart failure patients with either reduced or preserved ejection
      fraction, E(A)/E(LV) at rest is impaired. During dynamic exercise, E(A)/E(LV)
      decreases, due to an acute mismatch between the arterial and ventricular systems
      as E(LV) increases disproportionate compared to E(A) (~200 vs. 40%), to ensure
      that sufficient cardiac performance is achieved to meet the increased energetic
      requirements of the body. However, with advancing age the reduction in E(A)/E(LV)
      during acute maximal exercise is blunted, due to a blunted increase E(LV). This
      impaired E(A)/E(LV) is further amplified in the presence of disease, and may
      explain, in part, the reduced cardiovascular functional capacity with age and
      disease. Thus, although increased stiffness of the arteries itself has important
      physiological and clinical relevance, such changes also have major implications
      on the heart, and vice versa, and the manner in the way they interact has
      important ramifications on cardiovascular function both at rest and during
      exercise. Examination of the alterations in arterial-ventricular coupling with
      aging and disease can yield mechanistic insights into the pathophysiology of
      these conditions and increase the effectiveness of current therapeutic
      interventions.

PMID- 22586402
TI  - Computational modeling and numerical methods for spatiotemporal calcium cycling
      in ventricular myocytes.
AB  - Intracellular calcium (Ca) cycling dynamics in cardiac myocytes is regulated by a
      complex network of spatially distributed organelles, such as sarcoplasmic
      reticulum (SR), mitochondria, and myofibrils. In this study, we present a
      mathematical model of intracellular Ca cycling and numerical and computational
      methods for computer simulations. The model consists of a coupled Ca release unit
      (CRU) network, which includes a SR domain and a myoplasm domain. Each CRU
      contains 10 L-type Ca channels and 100 ryanodine receptor channels, with
      individual channels simulated stochastically using a variant of Gillespie's
      method, modified here to handle time-dependent transition rates. Both the SR
      domain and the myoplasm domain in each CRU are modeled by 5 * 5 * 5 voxels to
      maintain proper Ca diffusion. Advanced numerical algorithms implemented on
      graphical processing units were used for fast computational simulations. For a
      myocyte containing 100 * 20 * 10 CRUs, a 1-s heart time simulation takes about 10
      min of machine time on a single NVIDIA Tesla C2050. Examples of simulated Ca
      cycling dynamics, such as Ca sparks, Ca waves, and Ca alternans, are shown.

PMID- 22586403
TI  - Impact of KChIP2 on Cardiac Electrophysiology and the Progression of Heart
      Failure.
AB  - Electrophysiological remodeling of cardiac potassium ion channels is important in
      the progression of heart failure. A reduction of the transient outward potassium
      current (I(to)) in mammalian heart failure is consistent with a reduced
      expression of potassium channel interacting protein 2 (KChIP2, a K(V)4 subunit).
      Approaches have been made to investigate the role of KChIP2 in shaping cardiac
      I(to), including the use of transgenic KChIP2 deficient mice and viral
      overexpression of KChIP2. The interplay between I(to) and myocardial calcium
      handling is pivotal in the development of heart failure, and is further
      strengthened by the dual role of KChIP2 as a functional subunit on both K(V)4 and
      Ca(V)1.2. Moreover, the potential arrhythmogenic consequence of reduced I(to) may
      contribute to the high relative incidence of sudden death in the early phases of
      human heart failure. With this review, we offer an overview of the insights into
      the physiological and pathological roles of KChIP2 and we discuss the limitations
      of translating the molecular basis of electrophysiological remodeling from animal
      models of heart failure to the clinical setting.

PMID- 22586404
TI  - Osmotic gradients induce bio-reminiscent morphological transformations in giant
      unilamellar vesicles.
AB  - We report observations of large-scale, in-plane and out-of-plane membrane
      deformations in giant uni- and multilamellar vesicles composed of binary and
      ternary lipid mixtures in the presence of net transvesicular osmotic gradients.
      The lipid mixtures we examined consisted of binary mixtures of DOPC and DPPC
      lipids and ternary mixtures comprising POPC, sphingomyelin and cholesterol over a
      range of compositions - both of which produce co-existing phases for selected
      ranges of compositions at room temperature under thermodynamic equilibrium. In
      the presence of net osmotic gradients, we find that the in-plane phase separation
      potential of these mixtures is non-trivially altered and a variety of out-of
      plane morphological remodeling events occur. The repertoire of membrane
      deformations we observe display striking resemblance to their biological
      counterparts in live cells encompassing vesiculation, membrane fission and
      fusion, tubulation and pearling, as well as expulsion of entrapped vesicles from
      multicompartmental giant unilamellar vesicles through large, self-healing
      transient pores. These observations suggest that the forces introduced by simple
      osmotic gradients across membrane boundaries could act as a trigger for shape
      dependent membrane and vesicle trafficking activities. We speculate that such
      coupling of osmotic gradients with membrane properties might have provided lipid
      mediated mechanisms to compensate for osmotic stress during the early evolution
      of membrane compartmentalization in the absence of osmoregulatory protein
      machinery.

PMID- 22586405
TI  - Defects in cytoskeletal signaling pathways, arrhythmia, and sudden cardiac death.
AB  - Ankyrin polypeptides are cellular adapter proteins that tether integral membrane
      proteins to the cytoskeleton in a host of human organs. Initially identified as
      integral components of the cytoskeleton in erythrocytes, a recent explosion in
      ankyrin research has demonstrated that these proteins play prominent roles in
      cytoskeletal signaling pathways and membrane protein trafficking/regulation in a
      variety of excitable and non-excitable cells including heart and brain.
      Importantly, ankyrin research has translated from bench to bedside with the
      discovery of human gene variants associated with ventricular arrhythmias that
      alter ankyrin-based pathways. Ankyrin polypeptides have also been found to play
      an instrumental role in various forms of sinus node disease and atrial
      fibrillation (AF). Mouse models of ankyrin-deficiency have played fundamental
      roles in the translation of ankyrin-based research to new clinical understanding
      of human sinus node disease, AF, and ventricular tachycardia.

PMID- 22586406
TI  - The conundrum of functional brain networks: small-world efficiency or fractal
      modularity.
AB  - The human brain has been studied at multiple scales, from neurons, circuits,
      areas with well-defined anatomical and functional boundaries, to large-scale
      functional networks which mediate coherent cognition. In a recent work, we
      addressed the problem of the hierarchical organization in the brain through
      network analysis. Our analysis identified functional brain modules of fractal
      structure that were inter-connected in a small-world topology. Here, we provide
      more details on the use of network science tools to elaborate on this behavior.
      We indicate the importance of using percolation theory to highlight the modular
      character of the functional brain network. These modules present a fractal, self
      similar topology, identified through fractal network methods. When we lower the
      threshold of correlations to include weaker ties, the network as a whole assumes
      a small-world character. These weak ties are organized precisely as predicted by
      theory maximizing information transfer with minimal wiring costs.

PMID- 22586407
TI  - Role of Intrapancreatic SPINK1/Spink3 Expression in the Development of
      Pancreatitis.
AB  - Studies on hereditary pancreatitis have provided evidence in favor of central
      role for trypsin activity in the disease. Identification of genetic variants of
      trypsinogen linked the protease to the onset of pancreatitis, and biochemical
      characterization proposed an enzymatic gain of function as the initiating
      mechanism. Mutations of serine protease inhibitor Kazal type 1 gene (SPINK1) are
      shown to be associated with hereditary pancreatitis. We previously reported that
      Spink3 (a mouse homolog gene of human SPINK1) deficient mice showed excessive
      autophagy, followed by inappropriate trypsinogen activation in the exocrine
      pancreas. These data indicate that the role of SPINK1/Spink3 is not only trypsin
      inhibitor, but also negative regulator of autophagy. On the other hand, recent
      studies showed that high levels of SPINK1 protein detected in a serum or urine
      were associated with adverse outcome in various cancer types. It has been
      suggested that expression of SPINK1 and trypsin is balanced in normal tissue, but
      this balance could be disrupted during tumor progression. Based on the structural
      similarity between SPINK1 and epidermal growth factor (EGF), we showed that
      SPINK1 protein binds and activates EGF receptor, thus acting as a growth factor
      on tumor cell lines. In this review, we summarize the old and new roles of
      SPINK1/Spink3 in trypsin inhibition, autophagy, and cancer cell growth. These new
      functions of SPINK1/Spink3 may be related to the development of chronic
      pancreatitis.

PMID- 22586408
TI  - Measuring fractality.
AB  - WHEN INVESTIGATING FRACTAL PHENOMENA, THE FOLLOWING QUESTIONS ARE FUNDAMENTAL FOR
      THE APPLIED RESEARCHER: (1) What are essential statistical properties of 1/f
      noise? (2) Which estimators are available for measuring fractality? (3) Which
      measurement instruments are appropriate and how are they applied? The purpose of
      this article is to give clear and comprehensible answers to these questions.
      First, theoretical characteristics of a fractal pattern (self-similarity, long
      memory, power law) and the related fractal parameters (the Hurst coefficient, the
      scaling exponent alpha, the fractional differencing parameter d of the
      autoregressive fractionally integrated moving average methodology, the power
      exponent beta of the spectral analysis) are discussed. Then, estimators of
      fractal parameters from different software packages commonly used by applied
      researchers (R, SAS, SPSS) are introduced and evaluated. Advantages,
      disadvantages, and constrains of the popular estimators ([Formula: see text]
      power spectral density, detrended fluctuation analysis, signal summation
      conversion) are illustrated by elaborate examples. Finally, crucial steps of
      fractal analysis (plotting time series data, autocorrelation, and spectral
      functions; performing stationarity tests; choosing an adequate estimator;
      estimating fractal parameters; distinguishing fractal processes from short-memory
      patterns) are demonstrated with empirical time series.

PMID- 22586410
TI  - Urothelial TRPV1: TRPV1-Reporter Mice, a Way to Clarify the Debate?

PMID- 22586409
TI  - Vascular inflammatory cells in hypertension.
AB  - Hypertension is a common disorder with uncertain etiology. In the last several
      years, it has become evident that components of both the innate and adaptive
      immune system play an essential role in hypertension. Macrophages and T cells
      accumulate in the perivascular fat, the heart and the kidney of hypertensive
      patients, and in animals with experimental hypertension. Various
      immunosuppressive agents lower blood pressure and prevent end-organ damage. Mice
      lacking lymphocytes are protected against hypertension, and adoptive transfer of
      T cells, but not B cells in the animals restores their blood pressure response to
      stimuli such as angiotensin II or high salt. Recent studies have shown that mice
      lacking macrophages have blunted hypertension in response to angiotensin II and
      that genetic deletion of macrophages markedly reduces experimental hypertension.
      Dendritic cells have also been implicated in this disease. Many hypertensive
      stimuli have triggering effects on the central nervous system and signals arising
      from the circumventricular organ seem to promote inflammation. Studies have
      suggested that central signals activate macrophages and T cells, which home to
      the kidney and vasculature and release cytokines, including IL-6 and IL-17, which
      in turn cause renal and vascular dysfunction and lead to blood pressure
      elevation. These recent discoveries provide a new understanding of hypertension
      and provide novel therapeutic opportunities for treatment of this serious
      disease.

PMID- 22586412
TI  - The structural neural substrates of persistent negative symptoms in first-episode
      of non-affective psychosis: a voxel-based morphometry study.
AB  - OBJECTIVES: An important subset of patients with schizophrenia present clinically
      significant persistent negative symptoms (PNS). Identifying the neural substrates
      of PNS could help improve our understanding and treatment of these symptoms.
      METHODS: This study included 64 non-affective first-episode of psychosis (FEP)
      patients and 60 healthy controls; 16 patients displayed PNS (i.e., at least one
      primary negative symptom at moderate or worse severity sustained for at least six
      consecutive months). Using voxel-based morphometry (VBM), we explored for gray
      matter differences between PNS and non-PNS patients; patient groups were also
      compared to controls. All comparisons were performed at p < 0.05, corrected for
      multiple comparisons. RESULTS: PNS patients had smaller gray matter in the right
      frontal medial-orbital gyrus (extending into the inferior frontal gyrus) and
      right parahippocampal gyrus (extending into the fusiform gyrus) compared to non
      PNS patients. Compared to controls, PNS patients had smaller gray matter in the
      right parahippocampal gyrus (extending into the fusiform gyrus and superior
      temporal gyrus); non-PNS patients showed no significant differences to controls.
      CONCLUSION: Neural substrates of PNS are evident in FEP patients. A better
      understanding of the neural etiology of PNS may encourage the search for new
      medications and/or alternative treatments to better help those affected.

PMID- 22586411
TI  - Rett syndrome: genes, synapses, circuits, and therapeutics.
AB  - Development of the nervous system proceeds through a set of complex checkpoints
      which arise from a combination of sequential gene expression and early neural
      activity sculpted by the environment. Genetic and environmental insults lead to
      neurodevelopmental disorders which encompass a large group of diseases that
      result from anatomical and physiological abnormalities during maturation and
      development of brain circuits. Rett syndrome (RTT) is a neurological disorder of
      genetic origin, caused by mutations in the X-linked gene methyl-CpG binding
      protein 2 (MeCP2). It features a range of neuropsychiatric abnormalities
      including motor dysfunctions and mild to severe cognitive impairment. Here, we
      discuss key questions and recent studies describing animal models, cell-type
      specific functions of methyl-CpG binding protein 2 (MeCP2), defects in neural
      circuit plasticity, and attempts to evaluate possible therapeutic strategies for
      RTT. We also discuss how genes, proteins, and overlapping signaling pathways
      affect the molecular etiology of apparently unrelated neuropsychiatric disorders,
      an understanding of which can offer novel therapeutic strategies for a range of
      autism spectrum disorders (ASDs).

PMID- 22586413
TI  - Muscle or motivation? A stop-signal study on the effects of sequential cognitive
      control.
AB  - Performance on cognitive control tasks deteriorates when control tasks are
      performed together with other control tasks, that is, if simultaneous cognitive
      control is required. Surprisingly, this is also observed if control tasks are
      preceded by other control tasks, that is, if sequential cognitive control is
      required. The typical explanation for the latter finding is that previous acts of
      cognitive control deplete a common resource, just like a muscle becomes fatigued
      after repeated usage. An alternative explanation, however, is that previous acts
      of cognitive control reduce motivation to match allocated resources to required
      resources. In this paper we formalize these muscle and motivation accounts, and
      show that they yield differential predictions regarding the interaction between
      simultaneous and sequential cognitive control. These predictions were tested
      using a paradigm where participants had to perform multiple stop-signal tasks,
      which varied in their demands on simultaneous and sequential control. Results of
      two studies supported predictions derived from the motivation account. Therefore,
      we conclude that the effects of sequential cognitive control are best explained
      in terms of a reduction of motivation to match allocated to required resources.

PMID- 22586414
TI  - Free-energy minimization and the dark-room problem.
AB  - Recent years have seen the emergence of an important new fundamental theory of
      brain function. This theory brings information-theoretic, Bayesian,
      neuroscientific, and machine learning approaches into a single framework whose
      overarching principle is the minimization of surprise (or, equivalently, the
      maximization of expectation). The most comprehensive such treatment is the "free
      energy minimization" formulation due to Karl Friston (see e.g., Friston and
      Stephan, 2007; Friston, 2010a,b - see also Fiorillo, 2010; Thornton, 2010). A
      recurrent puzzle raised by critics of these models is that biological systems do
      not seem to avoid surprises. We do not simply seek a dark, unchanging chamber,
      and stay there. This is the "Dark-Room Problem." Here, we describe the problem
      and further unpack the issues to which it speaks. Using the same format as the
      prolog of Eddington's Space, Time, and Gravitation (Eddington, 1920) we present
      our discussion as a conversation between: an information theorist (Thornton), a
      physicist (Friston), and a philosopher (Clark).

PMID- 22586415
TI  - Does Filtering Preclude Us from Studying ERP Time-Courses?

PMID- 22586416
TI  - Predictive coding strategies for developmental neurorobotics.
AB  - In recent years, predictive coding strategies have been proposed as a possible
      means by which the brain might make sense of the truly overwhelming amount of
      sensory data available to the brain at any given moment of time. Instead of the
      raw data, the brain is hypothesized to guide its actions by assigning causal
      beliefs to the observed error between what it expects to happen and what actually
      happens. In this paper, we present a variety of developmental neurorobotics
      experiments in which minimalist prediction error-based encoding strategies are
      utilize to elucidate the emergence of infant-like behavior in humanoid robotic
      platforms. Our approaches will be first naively Piagian, then move onto more
      Vygotskian ideas. More specifically, we will investigate how simple forms of
      infant learning, such as motor sequence generation, object permanence, and
      imitation learning may arise if minimizing prediction errors are used as
      objective functions.

PMID- 22586417
TI  - Porcine head response to blast.
AB  - Recent studies have shown an increase in the frequency of traumatic brain
      injuries related to blast exposure. However, the mechanisms that cause blast
      neurotrauma are unknown. Blast neurotrauma research using computational models
      has been one method to elucidate that response of the brain in blast, and to
      identify possible mechanical correlates of injury. However, model validation
      against experimental data is required to ensure that the model output is
      representative of in vivo biomechanical response. This study exposes porcine
      subjects to primary blast overpressures generated using a compressed-gas shock
      tube. Shock tube blasts were directed to the unprotected head of each animal
      while the lungs and thorax were protected using ballistic protective vests
      similar to those employed in theater. The test conditions ranged from 110 to 740
      kPa peak incident overpressure with scaled durations from 1.3 to 6.9 ms and
      correspond approximately with a 50% injury risk for brain bleeding and apnea in a
      ferret model scaled to porcine exposure. Instrumentation was placed on the
      porcine head to measure bulk acceleration, pressure at the surface of the head,
      and pressure inside the cranial cavity. Immediately after the blast, 5 of the 20
      animals tested were apneic. Three subjects recovered without intervention within
      30 s and the remaining two recovered within 8 min following respiratory
      assistance and administration of the respiratory stimulant doxapram. Gross
      examination of the brain revealed no indication of bleeding. Intracranial
      pressures ranged from 80 to 390 kPa as a result of the blast and were notably
      lower than the shock tube reflected pressures of 300-2830 kPa, indicating
      pressure attenuation by the skull up to a factor of 8.4. Peak head accelerations
      were measured from 385 to 3845 G's and were well correlated with peak incident
      overpressure (R(2) = 0.90). One SD corridors for the surface pressure,
      intracranial pressure (ICP), and head acceleration are presented to provide
      experimental data for computer model validation.

PMID- 22586418
TI  - Vitreo-retinal hemorrhage after thrombolysis in a patient with acute ischemic
      stroke: a case report.
AB  - PURPOSE: Bleeding is the major side effect of thrombolysis with alteplase (tissue
      plasminogen activator, t-PA) used for the treatment of acute ischemic stroke.
      Life-threatening intracranial, retroperitoneal, gastrointestinal, respiratory,
      and genitourinary bleeding can occur with the use of t-PA. Vitreo-retinal
      bleeding in the context of acute ischemic stroke treatment has not been reported
      in the literature before and therefore is not posed as a potential risk during
      decision making. Here we describe the first reported case of vitreo-retinal
      hemorrhage due to alteplase administration in a patient with acute ischemic
      stroke. SUMMARY: An 84-year-old white male presented to the emergency room with
      complaints of right arm and leg weakness. The onset of symptoms was approximately
      30 min prior to presentation to the emergency room. After ruling out
      contraindications including the presence of hemorrhage on head CT scan, patient
      was administered alteplase within 2 hours of symptom onset. Four hours after the
      administration of alteplase, the patient developed right-sided vision changes. A
      repeat CT scan demonstrated a newly developed right intraocular hemorrhage.
      Throughout the hospital course, patient's neurological status improved, but he
      continued to have right-sided visual loss. CONCLUSION: Clinicians should be aware
      of the potential for ocular hemorrhage especially in high-risk patients. The
      likelihood of a subsequent vision-loss needs to be therefore discussed with the
      patient and family in such situations.

PMID- 22586420
TI  - The role of adjuvants in therapeutic protection against paracoccidioidomycosis
      after immunization with the P10 peptide.
AB  - Paracoccidioidomycosis (PCM), a common chronic mycosis in Latin America, is a
      granulomatous systemic disease caused by the thermo-dimorphic fungus
      Paracoccidioides brasiliensis. The glycoprotein gp43 is the main antigen target
      of P. brasiliensis and a 15-mer internal peptide (QTLIAIHTLAIRYAN), known as P10,
      defines a major CD4(+)-specific T cell epitope. Previous results have indicated
      that, besides having a preventive role in conventional immunizations prior to
      challenge with the fungus, protective anti-fungal effects can be induced in P.
      brasiliensis-infected mice treated with P10 administered with complete Freund's
      adjuvant (CFA). The peptide elicits an IFN-gamma-dependent Th1 immune response
      and is the main candidate for effective immunotherapy of patients with PCM, as an
      adjunctive approach to conventional chemotherapy. In the present study we tested
      the therapeutic effects of P10 combined with different adjuvants [aluminum
      hydroxide, CFA, flagellin, and the cationic lipid dioctadecyl-dimethylammonium
      bromide (DODAB)] in BALB/c mice previously infected with the P. brasiliensis Pb18
      strain. Significant reductions in the number of colony forming units of the
      fungus were detected in lungs of mice immunized with P10 associated with the
      different adjuvants 52 days after infection. Mice treated with DODAB and P10,
      followed by mice treated with P10 and flagellin, showed the most prominent
      effects as demonstrated by the lowest numbers of viable yeast cells as well as
      reductions in granuloma formation and fibrosis. Concomitantly, secretion of IFN
      gamma and TNF-alpha, in contrast to interleukin (IL)-4 and IL-10, was enhanced in
      the lungs of mice immunized with P10 in combination with the tested adjuvants,
      with the best results observed in mice treated with P10 and DODAB. In conclusion,
      the present results demonstrate that the co-administration of the synthetic P10
      peptide with several adjuvants, particularly DODAB, have significant therapeutic
      effects in experimental PCM.

PMID- 22586421
TI  - Impacts of microbial activity on the optical and copper-binding properties of
      leaf-litter leachate.
AB  - Dissolved organic matter (DOM) is a universal part of all aquatic systems that
      largely originates with the decay of plant and animal tissue. Its
      polyelectrolytic and heterogeneous characters make it an effective metal
      complexing agent with highly diverse characteristics. Microbes utilize DOM as a
      source of nutrients and energy and their enzymatic activity may change its
      composition, thereby altering the bioavailability and toxicity of metals. This
      study investigated the impacts of microbial inoculation upon the optical and
      copper-binding properties of freshly produced leaf-litter leachate over 168 h.
      Copper speciation was measured using voltammetry, and using fluorescence
      quenching analysis of independent fluorophores determined using parallel factor
      analysis (PARAFAC). Two protein/polyphenol-like and two fulvic/humic-like
      components were detected. Thirty-five percent of total protein/polyphenol-like
      fluorescence was removed after 168-h of exposure to riverine microbes. The
      microbial humic-like and tryptophan-like PARAFAC components retained
      significantly different log K values after 168 h of incubation (p < 0.05), while
      their complexing capacities were similar. Using voltammetry, a sixfold increase
      in copper-complexing capacity (CC, from 130 to 770 MUmol Cu g C(-1)) was observed
      over the exposure period, while the conditional binding constant (log K)
      decreased from 7.2 to 5.8. Overall binding parameters determined using
      voltammetry and fluorescence quenching were in agreement. However, the
      electrochemically based binding strength was significantly greater than that
      exhibited by any of the PARAFAC components, which may be due to the impact of non
      fluorescent DOM, or differences in the concentration ranges of metals analyzed
      (i.e., different analytical windows). It was concluded that the microbial
      metabolization of maple leaf leachate has a significant impact upon DOM
      composition and its copper-binding characteristics.

PMID- 22586419
TI  - Behavioral and psychological symptoms of dementia.
AB  - Behavioral and psychological symptoms of dementia (BPSD), also known as
      neuropsychiatric symptoms, represent a heterogeneous group of non-cognitive
      symptoms and behaviors occurring in subjects with dementia. BPSD constitute a
      major component of the dementia syndrome irrespective of its subtype. They are as
      clinically relevant as cognitive symptoms as they strongly correlate with the
      degree of functional and cognitive impairment. BPSD include agitation, aberrant
      motor behavior, anxiety, elation, irritability, depression, apathy,
      disinhibition, delusions, hallucinations, and sleep or appetite changes. It is
      estimated that BPSD affect up to 90% of all dementia subjects over the course of
      their illness, and is independently associated with poor outcomes, including
      distress among patients and caregivers, long-term hospitalization, misuse of
      medication, and increased health care costs. Although these symptoms can be
      present individually it is more common that various psychopathological features
      co-occur simultaneously in the same patient. Thus, categorization of BPSD in
      clusters taking into account their natural course, prognosis, and treatment
      response may be useful in the clinical practice. The pathogenesis of BPSD has not
      been clearly delineated but it is probably the result of a complex interplay of
      psychological, social, and biological factors. Recent studies have emphasized the
      role of neurochemical, neuropathological, and genetic factors underlying the
      clinical manifestations of BPSD. A high degree of clinical expertise is crucial
      to appropriately recognize and manage the neuropsychiatric symptoms in a patient
      with dementia. Combination of non-pharmacological and careful use of
      pharmacological interventions is the recommended therapeutic for managing BPSD.
      Given the modest efficacy of current strategies, there is an urgent need to
      identify novel pharmacological targets and develop new non-pharmacological
      approaches to improve the adverse outcomes associated with BPSD.

PMID- 22586422
TI  - Keys to eukaryality: planctomycetes and ancestral evolution of cellular
      complexity.
AB  - Planctomycetes are known to display compartmentalization via internal membranes,
      thus resembling eukaryotes. Significantly, the planctomycete Gemmata
      obscuriglobus has not only a nuclear region surrounded by a double-membrane, but
      is also capable of protein uptake via endocytosis. In order to clearly analyze
      implications for homology of their characters with eukaryotes, a correct
      understanding of planctomycete structure is an essential starting point. Here we
      outline the major features of such structure necessary for assessing the case for
      or against homology with eukaryote cell complexity. We consider an evolutionary
      model for cell organization involving reductive evolution of Planctomycetes from
      a complex proto-eukaryote-like last universal common ancestor, and evaluate
      alternative models for origins of the unique planctomycete cell plan. Overall,
      the structural and molecular evidence is not consistent with convergent evolution
      of eukaryote-like features in a bacterium and favors a homologous relationship of
      Planctomycetes and eukaryotes.

PMID- 22586423
TI  - Control of biogenic amines in fermented sausages: role of starter cultures.
AB  - Biogenic amines show biological activity and exert undesirable physiological
      effects when absorbed at high concentrations. Biogenic amines are mainly formed
      by microbial decarboxylation of amino acids and thus are usually present in a
      wide range of foods, fermented sausages being one of the major biogenic amine
      sources. The use of selected starter cultures is one of the best technological
      measures to control aminogenesis during meat fermentation. Although with variable
      effectiveness, several works show the ability of some starters to render biogenic
      amine-free sausages. In this paper, the effect of different starter culture is
      reviewed and the factors determining their performance discussed.

PMID- 22586424
TI  - Light Quantity Affects the Regulation of Cell Shape in Fremyella diplosiphon.
AB  - In some cyanobacteria, the color or prevalent wavelengths of ambient light can
      impact the protein or pigment composition of the light-harvesting complexes. In
      some cases, light color or quality impacts cellular morphology. The significance
      of changes in pigmentation is associated strongly with optimizing light
      absorption for photosynthesis, whereas the significance of changes in light
      quality-dependent cellular morphology is less well understood. In natural aquatic
      environments, light quality and intensity change simultaneously at varying depths
      of the water column. Thus, we hypothesize that changes in morphology that also
      have been attributed to differences in the prevalent wavelengths of available
      light may largely be associated with changes in light intensity. Fremyella
      diplosiphon shows highly reproducible light-dependent changes in pigmentation and
      morphology. Under red light (RL), F. diplosiphon cells are blue-green in color,
      due to the accumulation of high levels of phycocyanin, a RL-absorbing pigment in
      the light-harvesting complexes or phycobilisomes (PBSs), and the shape of cells
      are short and rounded. Conversely, under green light (GL), F. diplosiphon cells
      are red in color due to accumulation of GL-absorbing phycoerythrin in PBSs, and
      are longer and brick-shaped. GL is enriched at lower depths in the water column,
      where overall levels of light also are reduced, i.e., to 10% or less of the
      intensity found at the water surface. We hypothesize that longer cells under low
      light intensities at increasing depths in the water column, which are generally
      also enriched in green wavelengths, are associated with greater levels of total
      photosynthetic pigments in the thylakoid membranes. To test this hypothesis, we
      grew F. diplosiphon under increasing intensities of GL and observed whether the
      length of cells diminished due to reduced pressure to maintain larger cells and
      the associated increased photosynthetic membrane capacity under high light
      intensity, independent of whether it is light of green wavelengths.

PMID- 22586425
TI  - Biogenic amines in italian pecorino cheese.
AB  - The quality of distinctive artisanal cheeses is closely associated with the
      territory of production and its traditions. Pedoclimatic characteristics, genetic
      autochthonous variations, and anthropic components create an environment so
      specific that it would be extremely difficult to reproduce elsewhere. Pecorino
      cheese is included in this sector of the market and is widely diffused in Italy
      (~62.000t of production in 2010). Pecorino is a common name given to indicate
      Italian cheeses made exclusively from pure ewes' milk characterized by a high
      content of fat matter and it is mainly produced in the middle and south of Italy
      by traditional procedures from raw or pasteurized milk. The microbiota plays a
      major role in the development of the organoleptic characteristics of the cheese
      but it can also be responsible for the accumulation of undesirable substances,
      such as biogenic amines (BA). Bacterial amino acid decarboxylase activity and BA
      content have to be investigated within the complex microbial community of raw
      milk cheese for different cheese technologies. The results emphasize the
      necessity of controlling the indigenous bacterial population responsible for high
      production of BA and the use of competitive adjunct cultures could be suggested.
      Several factors can contribute to the qualitative and quantitative profiles of
      BA's in Pecorino cheese such as environmental hygienic conditions, pH, salt
      concentration, water activity, fat content, pasteurization of milk, decarboxylase
      microorganisms, starter cultures, temperature and time of ripening, storage, part
      of the cheese (core, edge), and the presence of cofactor (pyridoxal phosphate,
      availability of aminases and deaminases). In fact physico-chemical parameters
      seem to favor biogenic amine-positive microbiota; both of these environmental
      factors can easily be modulated, in order to control growth of undesirable
      microorganisms. Generally, the total content of BA's in Pecorino cheeses can
      range from about 100-2400 mg/kg, with a prevalence of toxicologically important
      BA's, tyramine and histamine. The presence of BA is becoming increasingly
      important to consumers and cheese-maker alike, due to the potential threats of
      toxicity to humans and consequent trade implications.

PMID- 22586426
TI  - Suitability of a probiotic Lactobacillus paracasei strain as a starter culture in
      olive fermentation and development of the innovative patented product "probiotic
      table olives".
AB  - Probiotic bacteria are generally available for consumers as concentrated
      preparations or incorporated in milk-based foods. Due to an increased interest of
      the market for probiotic foods as well as to meet a demand of industry for
      innovation, a new kind of probiotic food has been developed using table olives as
      a carrier. Green table olives, produced according to the Spanish-style, are
      obtained by a fermentation which can be carried out by spontaneous microflora,
      even if the use of starter cultures is desirable to obtain a more controlled
      process. In this regard, the selected strain Lactobacillus paracasei IMPC 2.1 of
      human origin was used in the dual role of starter and probiotic culture, and here
      we describe the different aspects which have been evaluated and solved to utilize
      that strain for the development of a new table olive-based probiotic food. These
      aspects include selection of the strain on the basis of its probiotic properties,
      molecular characterization, compatibility with the carrier food, and efficacy as
      starter. The final product meets commercial and functional requirements
      throughout its shelf-life.

PMID- 22586427
TI  - Pandemic H1N1 Influenza Infection and Vaccination in Humans Induces Cross
      Protective Antibodies that Target the Hemagglutinin Stem.
AB  - Most monoclonal antibodies (mAbs) generated from humans infected or vaccinated
      with the 2009 pandemic H1N1 (pdmH1N1) influenza virus targeted the hemagglutinin
      (HA) stem. These anti-HA stem mAbs mostly used IGHV1-69 and bound readily to
      epitopes on the conventional seasonal influenza and pdmH1N1 vaccines. The anti-HA
      stem mAbs neutralized pdmH1N1, seasonal influenza H1N1 and avian H5N1 influenza
      viruses by inhibiting HA-mediated fusion of membranes and protected against and
      treated heterologous lethal infections in mice with H5N1 influenza virus. This
      demonstrated that therapeutic mAbs could be generated a few months after the new
      virus emerged. Human immunization with the pdmH1N1 vaccine induced circulating
      antibodies that when passively transferred, protected mice from lethal,
      heterologous H5N1 influenza infections. We observed that the dominant
      heterosubtypic antibody response against the HA stem correlated with the relative
      absence of memory B cells against the HA head of pdmH1N1, thus enabling the rare
      heterosubtypic memory B cells induced by seasonal influenza and specific for
      conserved sites on the HA stem to compete for T-cell help. These results support
      the notion that broadly protective antibodies against influenza would be induced
      by successive vaccination with conventional influenza vaccines based on subtypes
      of HA in viruses not circulating in humans.

PMID- 22586428
TI  - Macroautophagy Regulation during HIV-1 Infection of CD4+ T Cells and Macrophages.
AB  - Autophagy is an intracellular mechanism whereby pathogens, particularly viruses,
      are destroyed in autolysosomes after their entry into targets cells. Therefore,
      to survive and replicate in host cells, viruses have developed multiple
      strategies to either counteract or exploit this process. The aim of this review
      is to outline the known relationships between HIV-1 and autophagy in CD4+ T
      lymphocytes and macrophages, two main HIV-1 cell targets. The differential
      regulation of autophagy in these two cell-types is highlighted and its potential
      consequences in terms of viral replication and physiopathology discussed.

PMID- 22586429
TI  - Roles for ca(2+) mobilization and its regulation in mast cell functions.
AB  - Mobilization of Ca(2+) in response to IgE receptor-mediated signaling is a key
      process in many aspects of mast cell function. Here we summarize our current
      understanding of the molecular bases for this process and the roles that it plays
      in physiologically relevant mast cell biology. Activation of IgE receptor
      signaling by antigen that crosslinks these complexes initiates Ca(2+)
      mobilization as a fast wave that is frequently followed by a series of Ca(2+)
      oscillations which are dependent on Ca(2+) influx-mediated by coupling of the
      endoplasmic reticulum luminal Ca(2+) sensor STIM1 to the calcium release
      activated calcium channel protein Orai1. Granule exocytosis depends on this
      process, together with the activation of protein kinase C isoforms, and specific
      roles for these signaling steps are beginning to be understood. Ca(2+)
      mobilization also plays important roles in stimulated exocytosis of recycling
      endosomes and newly synthesized cytokines, as well as in antigen-mediated
      chemotaxis of rat mucosal mast cells. Phosphoinositide metabolism plays key roles
      in all of these processes, and we highlight these roles in several cases.

PMID- 22586430
TI  - Chronic intestinal inflammation: inflammatory bowel disease and colitis
      associated colon cancer.
AB  - The inflammatory bowel diseases (IBD), including Crohn's disease (CD) and
      ulcerative colitis (UC), are chronic inflammatory disorders of the intestine. The
      prevalence in the United States is greater than 200 cases per 100,000, with the
      total number of IBD patients between 1 and 1.5 million. CD may affect all parts
      of the gastrointestinal tract, from mouth to anus, but most commonly involves the
      distal part of the small intestine or ileum, and colon. UC results in colonic
      inflammation that can affect the rectum only, or can progress proximally to
      involve part of or the entire colon. Clinical symptoms include diarrhea,
      abdominal pain, gastrointestinal bleeding, and weight loss. A serious long-term
      complication of chronic inflammation is the development of colorectal cancer. A
      genetic basis for IBD had long been recognized based on the increased familial
      risk. However, significant discordance for CD in twins, and a much less robust
      phenotypic concordance for UC, suggested additional factors play a role in
      disease pathogenesis, including environmental factors. In the past several years,
      progress in understanding the molecular basis of IBD has accelerated, beginning
      with the generation of animal models of colitis and progressing to the
      identification of specific genetic markers from candidate gene, gene linkage, and
      genome-wide association analyses. Genetic studies have also resulted in the
      recognition of the importance of environmental factors, particularly the crucial
      role of the gut microbiota in CD and UC. Altered immune responses to the normal
      intestinal flora are key factors in IBD pathogenesis. In this research topic, the
      genetic basis of IBD, the genetic and cellular alterations associated with
      colitis-associated colon cancer, and the emerging role of the intestinal
      microbiota and other environmental factors will be reviewed.

PMID- 22586431
TI  - Drosophila melanogaster as a model for lead neurotoxicology and toxicogenomics
      research.
AB  - Drosophila melanogaster is an excellent model animal for studying the
      neurotoxicology of lead. It has been known since ancient Roman times that long
      term exposure to low levels of lead results in behavioral abnormalities, such as
      what is now known as attention deficit hyperactivity disorder (ADHD). Because
      lead alters mechanisms that underlie developmental neuronal plasticity, chronic
      exposure of children, even at blood lead levels below the current CDC community
      action level (10 MUg/dl), can result in reduced cognitive ability, increased
      likelihood of delinquency, behaviors associated with ADHD, changes in activity
      level, altered sensory function, delayed onset of sexual maturity in girls, and
      changes in immune function. In order to better understand how lead affects
      neuronal plasticity, we will describe recent findings from a Drosophila
      behavioral genetics laboratory, a Drosophila neurophysiology laboratory, and a
      Drosophila quantitative genetics laboratory who have joined forces to study the
      effects of lead on the Drosophila nervous system. Studying the effects of lead on
      Drosophila nervous system development will give us a better understanding of the
      mechanisms of Pb neurotoxicity in the developing human nervous system.

PMID- 22586432
TI  - On the analysis of the illumina 450k array data: probes ambiguously mapped to the
      human genome.

PMID- 22586433
TI  - Medication use in the context of everyday living as understood by seniors.
AB  - Recognizing that older adults are among the biggest consumers of medication, and
      the demographic group most likely to suffer an adverse drug reaction (ADR), this
      paper details the findings from a recent study on how older adults come to
      understand medication and its related use. Using a qualitative content analysis
      method, semi-structured interviews were conducted with 21 individuals from
      British Columbia, Canada. Study participants ranged in age from 65 to 89 years
      (male=9, female=11). Using NVIVO((r)) 7 software, data were subjected to
      comparative thematic content analysis in an effort to capture the role of
      medication use in the context of everyday living as understood by older adults.
      While there was variability in how older adults come to understand their
      medication use, an overarching theme was revealed whereby most participants
      identified their prescription medications as being life-sustaining and
      prolonging. Deeper thematic content analysis of participant narratives drew
      attention to three key areas: (A) medications are viewed as a necessary, often
      unquestioned, aspect of day-to-day life (B) a relationship is perceived to exist
      between the amount of medications taken and ones current state of health (C) the
      overall medication experience is positively or negatively influenced by the
      doctor patient relationship and the assumption that it is the physicians role to
      communicate medication information that will support everyday living. The article
      concludes that medical authority and the complexities surrounding medication use
      need to undergo significant revision if community dwelling older adults are to
      experience greater success in safely managing their health and medication-related
      needs.

PMID- 22586434
TI  - Multiple cytokines are involved in the early events leading to the Alzheimer's
      disease pathology.
AB  - It is likely that neuroinflammation begins well before detectable cognitive
      impairment in Alzheimer's disease (AD) occurs. Clarifying the alterations
      occurring prior to the clinical manifestation of overt AD dementia may provide
      valuable insight into the early diagnosis and management of AD. Herein, to
      address the issue that neuroinflammation precedes development of AD pathology, we
      analyzed cytokine expression profiles of the brain, with focus on non-demented
      control patients with increasing AD pathology, referred to as high pathology
      control (HPC) cases, who provide an intermediate subset between AD and normal
      control cases referred to as low pathology control (LPC) cases. With a semi
      quantitative analysis of cytokine mRNA, among 15 cytokines and their related
      molecules tested, we found the involvement of eight: interleukin-1(IL-1) receptor
      antagonist (IL-1ra), IL-1 converting enzyme (ICE), IL-2, IL-6, IL-8, tumor
      necrosis factor (TNF) alpha, macrophage-colony stimulating factor (M-CSF) and
      transforming growth factor (TGF) beta1 during the development from LPC to HPC,
      while decreases in IL-1ra, IL-8, MCP-1 and TNFalpha, and an increase in TACE were
      implicated in the later development from HPC to AD. These findings indicate that
      neuroinflammation precedes the clinical manifestation of overt dementia, rather
      than being involved at the later stages of AD.

PMID- 22586439
TI  - Genome-wide search reveals the existence of a limited number of thyroid hormone
      receptor alpha target genes in cerebellar neurons.
AB  - Thyroid hormone (T3) has a major influence on cerebellum post-natal development.
      The major phenotypic landmark of exposure to low levels of T3 during development
      (hypothyroidism) in the cerebellum is the retarded inward migration of the most
      numerous cell type, granular neurons. In order to identify the direct genetic
      regulation exerted by T3 on cerebellar neurons and their precursors, we used
      microarray RNA hybridization to perform a time course analysis of T3 induced gene
      expression in primary cultures of cerebellar neuronal cell. These experiments
      suggest that we identified a small set of genes which are directly regulated,
      both in vivo and in vitro, during cerebellum post-natal development. These modest
      changes suggest that T3 does not acts directly on granular neurons and mainly
      indirectly influences the cellular interactions taking place during development.

PMID- 22586440
TI  - Five-year follow-up of parapapillary atrophy: the Beijing Eye Study.
AB  - PURPOSE: To assess longitudinal changes in parapapillary atrophy in the adult
      population of Greater Beijing. METHODS: The population-based Beijing Eye Study
      2006 included 3251 subjects who had participated in the Beijing Eye Study 2001
      and returned for re-examination. The mean age was 60.4 +/- 10.1 years. Using
      optic disc photographs, we measured parapapillary atrophy which was divided into
      alpha zone and beta zone. RESULTS: Overall progression rate of alpha zone was
      seen in 0.6 +/- 0.1% (95% confidence interval (CI):0.3,0.9) of the subjects and
      of beta zone in 8.2 +/- 0.5% (95%CI:7.2,9.1) of the subjects. In binary
      regression analysis, rate of progression of alpha zone was significantly
      associated higher age (P = 0.04) and the co-progression of zone Beta (P<0.001).
      Rate of progression of beta zone was significantly associated with higher age
      (P<0.001; odds ratio (OR):1.11;95%CI:1.10,1.14), higher intraocular pressure
      (P<0.001;OR:1.10;95%CI:1.05,1.14), higher myopic refractive error
      (P<0.001;OR:0.71; 95%CI:0.67,0.75), rural region of habitation (P = 0.002;OR:
      0.58; 95%CI:0.41,0.82), presence of glaucomatous optic nerve damage
      (P<0.001;OR:2.89; 95%CI:1.62,5.14), co-progression of alpha zone
      (P<0.001;OR:7.13;95%CI:2.43,20.9), absence of arterial hypertension (P = 0.03;OR:
      0.70; 95%CI:0.51,0.96), and thicker central corneal thickness (P =
      0.02;OR:1.01;95%CI:1.00,1.01). Subjects with a non-glaucomatous optic nerve
      damage (n = 22) as compared to the remaining subjects did not vary in the
      progression rate of alpha zone (0.0% versus 0.6 +/- 0.1%; P = 1.0) and beta zone
      (8.2 +/- 0.5% versus 6.3 +/- 0.6%;P = 1.0). CONCLUSIONS: In adult Chinese in
      Greater Beijing, the 5-year progression rate of beta zone of parapapillary
      atrophy (seen in 8.2 +/- 0.5% of subjects) was significantly correlated with
      higher age, rural region of habitation, absence of arterial hypertension, higher
      intraocular pressure, higher myopic refractive error, thicker central corneal
      thickness, and presence of glaucoma. It was not associated with non-glaucomatous
      optic nerve damage.

PMID- 22586441
TI  - Association of human leukocyte antigen with interstitial lung disease in
      rheumatoid arthritis: a protective role for shared epitope.
AB  - INTRODUCTION: Interstitial Lung Disease (ILD) is frequently associated with
      Rheumatoid Arthritis (RA) as one of extra-articular manifestations. Many studies
      for Human Leukocyte Antigen (HLA) allelic association with RA have been reported,
      but few have been validated in an RA subpopulation with ILD. In this study, we
      investigated the association of HLA class II alleles with ILD in RA. METHODS: An
      association study was conducted on HLA-DRB1, DQB1, and DPB1 in 450 Japanese RA
      patients that were or were not diagnosed with ILD, based on the findings of
      computed tomography images of the chest. RESULTS: Unexpectedly, HLA-DRB1*04
      (corrected P [Pc] = 0.0054, odds ratio [OR] 0.57), shared epitope (SE) (P =
      0.0055, OR 0.66) and DQB1*04 (Pc = 0.0036, OR 0.57) were associated with
      significantly decreased risk of ILD. In contrast, DRB1*16 (Pc = 0.0372, OR
      15.21), DR2 serological group (DRB1*15 and *16 alleles) (P = 0.0020, OR 1.75) and
      DQB1*06 (Pc = 0.0333, OR 1.57, respectively) were significantly associated with
      risk of ILD. CONCLUSION: HLA-DRB1 SE was associated with reduced, while DR2
      serological group (DRB1*15 and *16) with increased, risk for ILD in Japanese
      patients with RA.

PMID- 22586442
TI  - Frequency and risk indicators of tooth decay among pregnant women in France: a
      cross-sectional analysis.
AB  - INTRODUCTION: Little is known on the prevalence of tooth decay among pregnant
      women. Better knowledge of tooth decay risk indicators during pregnancy could
      help to develop follow-up protocols for women at risk, along with better
      prevention strategies. The aim of this study was to assess the frequency of tooth
      decay and the number of decayed teeth per woman in a large sample of pregnant
      women in France, and to study associated risk indicators. METHODS: A secondary
      cross-sectional analysis of data from a French multicentre case-control study was
      performed. The sample was composed of 1094 at-term women of six maternity units.
      A dental examination was carried out within 2 to 4 days post-partum. Socio
      demographic and behavioural characteristics were obtained through a standardised
      interview with the women. Medical characteristics were obtained from the women's
      medical records. Risk indicators associated with tooth decay were identified
      using a negative binomial hurdle model. RESULTS: 51.6% of the women had tooth
      decay. The mean number of decayed teeth among women having at least one was 3.1
      (s.d. = 2.8). Having tooth decay was statistically associated with lower age (aOR
      = 1.58, 95%CI [1.03,2.45]), lower educational level (aOR = 1.53, 95%CI
      [1.06,2.23]) and dental plaque (aOR = 1.75, 95%CI [1.27,2.41]). The number of
      decayed teeth was associated with the same risk indicators and with non-French
      nationality and inadequate prenatal care. DISCUSSION: The frequency of tooth
      decay and the number of decayed teeth among pregnant women were high. Oral health
      promotion programmes must continue to inform women and care providers about the
      importance of dental care before, during and after pregnancy. Future research
      should also assess the effectiveness of public policies related to oral health in
      target populations of pregnant women facing challenging social or economic
      situations.

PMID- 22586443
TI  - Single cell profiling of circulating tumor cells: transcriptional heterogeneity
      and diversity from breast cancer cell lines.
AB  - BACKGROUND: To improve cancer therapy, it is critical to target metastasizing
      cells. Circulating tumor cells (CTCs) are rare cells found in the blood of
      patients with solid tumors and may play a key role in cancer dissemination.
      Uncovering CTC phenotypes offers a potential avenue to inform treatment. However,
      CTC transcriptional profiling is limited by leukocyte contamination; an approach
      to surmount this problem is single cell analysis. Here we demonstrate feasibility
      of performing high dimensional single CTC profiling, providing early insight into
      CTC heterogeneity and allowing comparisons to breast cancer cell lines widely
      used for drug discovery. METHODOLOGY/PRINCIPAL FINDINGS: We purified CTCs using
      the MagSweeper, an immunomagnetic enrichment device that isolates live tumor
      cells from unfractionated blood. CTCs that met stringent criteria for further
      analysis were obtained from 70% (14/20) of primary and 70% (21/30) of metastatic
      breast cancer patients; none were captured from patients with non-epithelial
      cancer (n = 20) or healthy subjects (n = 25). Microfluidic-based single cell
      transcriptional profiling of 87 cancer-associated and reference genes showed
      heterogeneity among individual CTCs, separating them into two major subgroups,
      based on 31 highly expressed genes. In contrast, single cells from seven breast
      cancer cell lines were tightly clustered together by sample ID and ER status. CTC
      profiles were distinct from those of cancer cell lines, questioning the
      suitability of such lines for drug discovery efforts for late stage cancer
      therapy. CONCLUSIONS/SIGNIFICANCE: For the first time, we directly measured high
      dimensional gene expression in individual CTCs without the common practice of
      pooling such cells. Elevated transcript levels of genes associated with
      metastasis NPTN, S100A4, S100A9, and with epithelial mesenchymal transition: VIM,
      TGFbeta1, ZEB2, FOXC1, CXCR4, were striking compared to cell lines. Our findings
      demonstrate that profiling CTCs on a cell-by-cell basis is possible and may
      facilitate the application of 'liquid biopsies' to better model drug discovery.

PMID- 22586444
TI  - Insight into the assembly properties and functional organisation of the
      magnetotactic bacterial actin-like homolog, MamK.
AB  - Magnetotactic bacteria (MTB) synthesize magnetosomes, which are intracellular
      vesicles comprising a magnetic particle. A series of magnetosomes arrange
      themselves in chains to form a magnetic dipole that enables the cell to orient
      itself along the Earth's magnetic field. MamK, an actin-like homolog of MreB has
      been identified as a central component in this organisation. Gene deletion,
      fluorescence microscopy and in vitro studies have yielded mechanistic differences
      in the filament assembly of MamK with other bacterial cytoskeletal proteins
      within the cell. With little or no information on the structural and behavioural
      characteristics of MamK outside the cell, the mamK gene from Magnetospirillium
      gryphiswaldense was cloned and expressed to better understand the differences in
      the cytoskeletal properties with its bacterial homologues MreB and acitin.
      Despite the low sequence identity shared between MamK and MreB (22%) and actin
      (18%), the behaviour of MamK monitored by light scattering broadly mirrored that
      of its bacterial cousin MreB primarily in terms of its pH, salt, divalent metal
      ion and temperature dependency. The broad size variability of MamK filaments
      revealed by light scattering studies was supported by transmission electron
      microscopy (TEM) imaging. Filament morphology however, indicated that MamK
      conformed to linearly orientated filaments that appeared to be distinctly
      dissimilar compared to MreB suggesting functional differences between these
      homologues. The presence of a nucleotide binding domain common to actin-like
      proteins was demonstrated by its ability to function both as an ATPase and
      GTPase. Circular dichroism and structural homology modelling showed that MamK
      adopts a protein fold that is consistent with the 'classical' actin family
      architecture but with notable structural differences within the smaller domains,
      the active site region and the overall surface electrostatic potential.

PMID- 22586445
TI  - Describing and quantifying asthma comorbidity [corrected]: a population study.
AB  - BACKGROUND: Asthma comorbidity has been correlated with poor asthma control,
      increased health services use, and decreased quality of life. Managing it
      improves these outcomes. Little is known about the amount of different types of
      comorbidity associated with asthma and how they vary by age.
      METHODOLOGY/PRINCIPAL FINDINGS: The authors conducted a population study using
      health administrative data on all individuals living in Ontario, Canada
      (population 12 million). Types of asthma comorbidity were quantified by comparing
      physician health care claims between individuals with and without asthma in each
      of 14 major disease categories; results were adjusted for demographic factors and
      other comorbidity and stratified by age. Compared to those without asthma,
      individuals with asthma had higher rates of comorbidity in most major disease
      categories. Most notably, they had about fifty percent or more physician health
      care claims for respiratory disease (other than asthma) in all age groups;
      psychiatric disorders in individuals age four and under and age 18 to 44;
      perinatal disorders in individuals 17 years and under, and metabolic and
      immunity, and hematologic disorders in children four years and under.
      CONCLUSION/SIGNIFICANCE: Asthma appears to be associated with significant rates
      of various types of comorbidity that vary according to age. These results can be
      used to develop strategies to recognize and address asthma comorbidity to improve
      the overall health of individuals with asthma.

PMID- 22586446
TI  - Molecular epidemiology and evolution of human enterovirus serotype 68 in
      Thailand, 2006-2011.
AB  - BACKGROUND: Publications worldwide have reported on the re-occurrence of human
      enterovirus 68 (EV68), a rarely detected pathogen usually causing respiratory
      illness. However, epidemiological data regarding this virus in particular on the
      Asian continent has so far been limited. METHODOLOGY/FINDINGS: We investigated
      the epidemiology and genetic variability of EV68 infection among Thai children
      with respiratory illnesses from 2006-2011 (n = 1810). Semi-nested PCR using
      primer sets for amplification of the 5'-untranslated region through VP2 was
      performed for rhino-enterovirus detection. Altogether, 25 cases were confirmed as
      EV68 infection indicating a prevalence of 1.4% in the entire study population.
      Interestingly, the majority of samples were children aged >5 years (64%). Also,
      co-infection with other viruses was found in 28%, while pandemic H1N1
      influenza/2009 virus was the most common co-infection. Of EV68-positive patients,
      36% required hospitalizations with the common clinical presentations of fever,
      cough, dyspnea, and wheezing. The present study has shown that EV68 was extremely
      rare until 2009 (0.9%). An increasing annual prevalence was found in 2010 (1.6%)
      with the highest detection frequency in 2011 (4.3%). Based on analysis of the VP1
      gene, the evolutionary rate of EV68 was estimated at 4.93 * 10(-3)
      substitutions/site/year. Major bifurcation of the currently circulating EV68
      strains occurred 66 years ago (1945.31 with (1925.95-1960.46)95% HPD). Among the
      current lineages, 3 clusters of EV68 were categorized based on the different
      molecular signatures in the BC and DE loops of VP1 combined with high posterior
      probability values. Each cluster has branched off from their common ancestor at
      least 36 years ago (1975.78 with (1946.13-1984.97)95% HPD). CONCLUSION:
      Differences in epidemiological characteristic and seasonal profile of EV68 have
      been found in this study. Results from Bayesian phylogenetic investigations also
      revealed that EV68 should be recognized as a genetically diverse virus with a
      substitution rate identical to that of enterovirus 71 genotype B (4.2 * 10(-3
      )s/s/y).

PMID- 22586447
TI  - Polymorphism rs4919510:C>G in mature sequence of human microRNA-608 contributes
      to the risk of HER2-positive breast cancer but not other subtypes.
AB  - BACKGROUND: A few polymorphisms are located in the mature microRNA sequences.
      Such polymorphisms could directly affect the binding of microRNA to hundreds of
      target mRNAs. It remains unknown whether rs4919510:C>G located in the mature miR
      608 alters breast cancer susceptibility. METHODS: The association of
      rs4919510:C>G with risk and pathologic features of breast cancer were
      investigated in two independent case-control studies, the first set including
      1,138 sporadic breast cancer patients (including 927 invasive ductal carcinoma
      patients, 777 of them with known subtypes: 496 luminal-like, 133 HER2-positive,
      and 148 triple-negative) and 1,434 community-based controls, and the second set
      including 294 familial/early-onset breast cancer patients and 500 hospital-based
      cancer-free controls. Odds ratios (ORs) were estimated by logistic regression.
      Predicted targets of miR-608 and complementary sequences containing rs4919510:C>G
      were surveyed to reveal potential pathological mechanism. RESULTS: In the first
      set, although rs4919510:C>G was unrelated to breast cancer in general patients,
      variant genotypes (CG/GG) were specifically associated with increased risk of
      HER2-positive subtype (Adjusted OR = 1.97, 95% CI, 1.34-2.90 in the recessive
      model). Variant G-allele was the risk allele with OR of 1.62 (95% CI, 1.23-2.15).
      Patients carrying GG-genotype also had larger HER2-positive tumors (P for Kruskal
      Wallis test = 0.006). The relationship between rs4919510:C>G and risk of HER2
      positive subgroup was validated in the second set (Bonferroni corrected P =
      0.06). The adjusted combined OR (total 164 HER2-positive cases) in the recessive
      model was 1.97 (95% CI, 1.43-2.72) for GG genotype (corrected P = 1.1 * 10(-4)).
      Bioinformatic analysis indicated that, HSF1, which is required for HER2-induced
      tumorigenesis, might be a target of miR-608. The minimum free-energy of ancestral
      miR-608 (C-allele) binding to HSF1 is -35.9 kcal/mol, while that of variant-form
      (G-allele) is -31.5 kcal/mol, indicating a lower affinity of variant-miR-608 to
      HSF1 mRNA. CONCLUSION: rs4919510:C>G in mature miR-608 may influence HER2
      positive breast cancer risk and tumor proliferation.

PMID- 22586448
TI  - Nicotinic acetylcholine receptor agonists attenuate septic acute kidney injury in
      mice by suppressing inflammation and proteasome activity.
AB  - Sepsis is one of the leading causes of acute kidney injury (AKI). Septic patients
      who develop acute kidney injury (AKI) are at increased risk of death. To date
      there is no effective treatment for AKI or septic AKI. Based on their anti
      inflammatory properties, we examined the effects of nicotinic acetylcholine
      receptor agonists on renal damage using a mouse model of lipopolysaccharide (LPS)
      induced AKI where localized LPS promotes inflammation-mediated kidney damage.
      Administration of nicotine (1 mg/kg) or GTS-21 (4 mg/kg) significantly abrogated
      renal leukocyte infiltration (by 40%) and attenuated kidney injury. These
      renoprotective effects were accompanied by reduced systemic and localized kidney
      inflammation during LPS-induced AKI. Consistent with these observations,
      nicotinic agonist treatment significantly decreased renal IkappaBalpha
      degradation and NFkappaB activation during LPS-induced AKI. Treatment of human
      kidney cells with nicotinic agonists, an NFkappaB inhibitor (Bay11), or a
      proteasome inhibitor (MG132) effectively inhibited their inflammatory responses
      following stimulation with LPS or TNFalpha. Renal proteasome activity, a major
      regulator of NFkappaB-mediated inflammation, was enhanced by approximately 50%
      during LPS-induced AKI and elevated proteasome activity was significantly blunted
      by nicotinic agonist administration in vivo. Taken together, our results identify
      enhanced renal proteasome activity during LPS-induced AKI and the suppression of
      both proteasome activity and inflammation by nicotinic agonists to attenuate LPS
      induced kidney injury.

PMID- 22586449
TI  - Learning transcriptional regulatory relationships using sparse graphical models.
AB  - Understanding the organization and function of transcriptional regulatory
      networks by analyzing high-throughput gene expression profiles is a key problem
      in computational biology. The challenges in this work are 1) the lack of complete
      knowledge of the regulatory relationship between the regulators and the
      associated genes, 2) the potential for spurious associations due to confounding
      factors, and 3) the number of parameters to learn is usually larger than the
      number of available microarray experiments. We present a sparse (L1 regularized)
      graphical model to address these challenges. Our model incorporates known
      transcription factors and introduces hidden variables to represent possible
      unknown transcription and confounding factors. The expression level of a gene is
      modeled as a linear combination of the expression levels of known transcription
      factors and hidden factors. Using gene expression data covering 39,296
      oligonucleotide probes from 1109 human liver samples, we demonstrate that our
      model better predicts out-of-sample data than a model with no hidden variables.
      We also show that some of the gene sets associated with hidden variables are
      strongly correlated with Gene Ontology categories. The software including source
      code is available at http://grnl1.codeplex.com.

PMID- 22586450
TI  - gamma Sulphate PNA (PNA S): highly selective DNA binding molecule showing
      promising antigene activity.
AB  - Peptide Nucleic Acids (PNAs), nucleic acid analogues showing high stability to
      enzyme degradation and strong affinity and specificity of binding toward DNA and
      RNA are widely investigated as tools to interfere in gene expression. Several
      studies have been focused on PNA analogues with modifications on the backbone and
      bases in the attempt to overcome solubility, uptake and aggregation issues. gamma
      PNAs, PNA derivatives having a substituent in the gamma position of the backbone
      show interesting properties in terms of secondary structure and affinity of
      binding toward complementary nucleic acids. In this paper we illustrate our
      results obtained on new analogues, bearing a sulphate in the gamma position of
      the backbone, developed to be more DNA-like in terms of polarity and charge. The
      synthesis of monomers and oligomers is described. NMR studies on the
      conformational properties of monomers and studies on the secondary structure of
      single strands and triplexes are reported. Furthermore the hybrid stability and
      the effect of mismatches on the stability have also been investigated. Finally,
      the ability of the new analogue to work as antigene, interfering with the
      transcription of the ErbB2 gene on a human cell line overexpressing ErbB2
      (SKBR3), assessed by FACS and qPCR, is described.

PMID- 22586451
TI  - Generation of NSE-MerCreMer transgenic mice with tamoxifen inducible Cre activity
      in neurons.
AB  - To establish a genetic tool for conditional deletion or expression of gene in
      neurons in a temporally controlled manner, we generated a transgenic mouse (NSE
      MerCreMer), which expressed a tamoxifen inducible type of Cre recombinase
      specifically in neurons. The tamoxifen inducible Cre recombinase (MerCreMer) is a
      fusion protein containing Cre recombinase with two modified estrogen receptor
      ligand binding domains at both ends, and is driven by the neural-specific rat
      neural specific enolase (NSE) promoter. A total of two transgenic lines were
      established, and expression of MerCreMer in neurons of the central and enteric
      nervous systems was confirmed. Transcript of MerCreMer was detected in several
      non-neural tissues such as heart, liver, and kidney in these lines. In the
      background of the Cre reporter mouse strain Rosa26R, Cre recombinase activity was
      inducible in neurons of adult NSE-MerCreMer mice treated with tamoxifen by
      intragastric gavage, but not in those fed with corn oil only. We conclude that
      NSE-MerCreMer lines will be useful for studying gene functions in neurons for the
      conditions that Cre-mediated recombination resulting in embryonic lethality,
      which precludes investigation of gene functions in neurons through later stages
      of development and in adult.

PMID- 22586452
TI  - Predicting spike occurrence and neuronal responsiveness from LFPs in primary
      somatosensory cortex.
AB  - Local Field Potentials (LFPs) integrate multiple neuronal events like synaptic
      inputs and intracellular potentials. LFP spatiotemporal features are particularly
      relevant in view of their applications both in research (e.g. for understanding
      brain rhythms, inter-areal neural communication and neuronal coding) and in the
      clinics (e.g. for improving invasive Brain-Machine Interface devices). However
      the relation between LFPs and spikes is complex and not fully understood. As
      spikes represent the fundamental currency of neuronal communication this gap in
      knowledge strongly limits our comprehension of neuronal phenomena underlying
      LFPs. We investigated the LFP-spike relation during tactile stimulation in
      primary somatosensory (S-I) cortex in the rat. First we quantified how reliably
      LFPs and spikes code for a stimulus occurrence. Then we used the information
      obtained from our analyses to design a predictive model for spike occurrence
      based on LFP inputs. The model was endowed with a flexible meta-structure whose
      exact form, both in parameters and structure, was estimated by using a multi
      objective optimization strategy. Our method provided a set of nonlinear simple
      equations that maximized the match between models and true neurons in terms of
      spike timings and Peri Stimulus Time Histograms. We found that both LFPs and
      spikes can code for stimulus occurrence with millisecond precision, showing,
      however, high variability. Spike patterns were predicted significantly above
      chance for 75% of the neurons analysed. Crucially, the level of prediction
      accuracy depended on the reliability in coding for the stimulus occurrence. The
      best predictions were obtained when both spikes and LFPs were highly responsive
      to the stimuli. Spike reliability is known to depend on neuron intrinsic
      properties (i.e. on channel noise) and on spontaneous local network fluctuations.
      Our results suggest that the latter, measured through the LFP response
      variability, play a dominant role.

PMID- 22586453
TI  - Enhanced extinction of aversive memories by high-frequency stimulation of the rat
      infralimbic cortex.
AB  - Electrical stimulation of the rodent medial prefrontal cortex (mPFC), including
      the infralimbic cortex (IL), immediately prior to or during fear extinction
      training facilitates extinction memory. Here we examined the effects of high
      frequency stimulation (HFS) of the rat IL either prior to conditioning or
      following retrieval of the conditioned memory, on extinction of Pavlovian fear
      and conditioned taste aversion (CTA). IL-HFS applied immediately after fear
      memory retrieval, but not three hours after retrieval or prior to conditioning,
      subsequently reduced freezing during fear extinction. Similarly, IL-HFS given
      immediately, but not three hours after, retrieval of a CTA memory reduced
      aversion during extinction. These data indicate that HFS of the IL may be an
      effective method for reducing both learned fear and learned aversion.

PMID- 22586455
TI  - When do objects become landmarks? A VR study of the effect of task relevance on
      spatial memory.
AB  - We investigated how objects come to serve as landmarks in spatial memory, and
      more specifically how they form part of an allocentric cognitive map.
      Participants performing a virtual driving task incidentally learned the layout of
      a virtual town and locations of objects in that town. They were subsequently
      tested on their spatial and recognition memory for the objects. To assess whether
      the objects were encoded allocentrically we examined pointing consistency across
      tested viewpoints. In three experiments, we found that spatial memory for objects
      at navigationally relevant locations was more consistent across tested
      viewpoints, particularly when participants had more limited experience of the
      environment. When participants' attention was focused on the appearance of
      objects, the navigational relevance effect was eliminated, whereas when their
      attention was focused on objects' locations, this effect was enhanced, supporting
      the hypothesis that when objects are processed in the service of navigation,
      rather than merely being viewed as objects, they engage qualitatively distinct
      attentional systems and are incorporated into an allocentric spatial
      representation. The results are consistent with evidence from the neuroimaging
      literature that when objects are relevant to navigation, they not only engage the
      ventral "object processing stream", but also the dorsal stream and medial
      temporal lobe memory system classically associated with allocentric spatial
      memory.

PMID- 22586456
TI  - What parents of children who have received emergency care think about deferring
      consent in randomised trials of emergency treatments: postal survey.
AB  - OBJECTIVE: To investigate parents' views about deferred consent to inform
      management of trial disclosure after a child's death. METHODS: A postal
      questionnaire survey was sent to members of the Meningitis Research Foundation UK
      charity, whose child had suffered from bacterial meningitis or meningococcal
      septicaemia within the previous 5 years. Main outcome measures were acceptability
      of deferred consent; timing of requesting consent; and the management of
      disclosure of the trial after a child's death. RESULTS: 220 families were sent
      questionnaires of whom 63 (29%) were bereaved. 68 families responded (31%), of
      whom 19 (28%) were bereaved. The majority (67%) was willing for their child to be
      involved in the trial without the trial being explained to them beforehand; 70%
      wanted to be informed about the trial as soon as their child's condition had
      stabilised. In the event of a child's death before the trial could be discussed
      the majority of bereaved parents (66% 12/18) anticipated wanting to be told about
      the trial at some time. This compared with 37% (18/49) of non-bereaved families
      (p = 0.06). Parents' free text responses indicated that the word 'trial' held
      strongly negative connotations. A few parents regarded gaps in the evidence base
      about emergency treatments as indicating staff lacked expertise to care for a
      critically ill child. Bereaved parents' free text responses indicated the
      importance of individualised management of disclosure about a trial following a
      child's death. DISCUSSION: Deferred consent is acceptable to the majority of
      respondents. Parents whose children had recovered differed in their views
      compared to bereaved parents. Most bereaved parents would want to be informed
      about the trial in the aftermath of a child's death, although a minority strongly
      opposed such disclosure. Distinction should be drawn between the views of
      bereaved and non-bereaved parents when considering the acceptability of different
      consent processes.

PMID- 22586454
TI  - Exposure to lipopolysaccharide and/or unconjugated bilirubin impair the integrity
      and function of brain microvascular endothelial cells.
AB  - BACKGROUND: Sepsis and jaundice are common conditions in newborns that can lead
      to brain damage. Though lipopolysaccharide (LPS) is known to alter the integrity
      of the blood-brain barrier (BBB), little is known on the effects of unconjugated
      bilirubin (UCB) and even less on the joint effects of UCB and LPS on brain
      microvascular endothelial cells (BMEC). METHODOLOGY/PRINCIPAL FINDINGS:
      Monolayers of primary rat BMEC were treated with 1 ug/ml LPS and/or 50 uM UCB, in
      the presence of 100 uM human serum albumin, for 4 or 24 h. Co-cultures of BMEC
      with astroglial cells, a more complex BBB model, were used in selected
      experiments. LPS led to apoptosis and UCB induced both apoptotic and necrotic
      like cell death. LPS and UCB led to inhibition of P-glycoprotein and activation
      of matrix metalloproteinases-2 and -9 in mono-cultures. Transmission electron
      microscopy evidenced apoptotic bodies, as well as damaged mitochondria and rough
      endoplasmic reticulum in BMEC by either insult. Shorter cell contacts and
      increased caveolae-like invaginations were noticeable in LPS-treated cells and
      loss of intercellular junctions was observed upon treatment with UCB. Both
      compounds triggered impairment of endothelial permeability and transendothelial
      electrical resistance both in mono- and co-cultures. The functional changes were
      confirmed by alterations in immunostaining for junctional proteins beta-catenin,
      ZO-1 and claudin-5. Enlargement of intercellular spaces, and redistribution of
      junctional proteins were found in BMEC after exposure to LPS and UCB.
      CONCLUSIONS: LPS and/or UCB exert direct toxic effects on BMEC, with distinct
      temporal profiles and mechanisms of action. Therefore, the impairment of brain
      endothelial integrity upon exposure to these neurotoxins may favor their access
      to the brain, thus increasing the risk of injury and requiring adequate clinical
      management of sepsis and jaundice in the neonatal period.

PMID- 22586457
TI  - Plasma Plasmodium falciparum histidine-rich protein-2 concentrations are
      associated with malaria severity and mortality in Tanzanian children.
AB  - Plasma Plasmodium falciparum histidine-rich protein-2 (PfHRP-2) concentrations, a
      measure of parasite biomass, have been correlated with malaria severity in
      adults, but not yet in children. We measured plasma PfHRP-2 in Tanzanian children
      with uncomplicated (n = 61) and cerebral malaria (n = 45; 7 deaths). Median
      plasma PfHRP-2 concentrations were higher in cerebral malaria (1008 [IQR 342
      2572] ng/mL) than in uncomplicated malaria (465 [IQR 36-1426] ng/mL; p = 0.017).
      In cerebral malaria, natural log plasma PfHRP-2 was associated with coma depth (r
      = -0.42; p = 0.006) and mortality (OR: 3.0 [95% CI 1.03-8.76]; p = 0.04). In this
      relatively small cohort study in a mesoendemic transmission area of Africa,
      plasma PfHRP-2 was associated with pediatric malaria severity and mortality.
      Further studies among children in areas of Africa with higher malaria
      transmission and among children with different clinical manifestations of severe
      malaria will help determine the wider utility of quantitative PfHRP-2 as a
      measure of parasite biomass and prognosis in sub-Saharan Africa.

PMID- 22586458
TI  - Intestinal inflammation responds to microbial tissue load independent of
      pathogen/non-pathogen discrimination.
AB  - The intestinal immune system mounts inflammatory responses to pathogens but
      tolerates harmless commensal microbiota. Various mechanisms for pathogen/non
      pathogen discrimination have been proposed but their general relevance for
      inflammation control is unclear. Here, we compared intestinal responses to
      pathogenic Salmonella and non-pathogenic E. coli. Both microbes entered
      intestinal Peyer's patches and, surprisingly, induced qualitatively and
      quantitatively similar initial inflammatory responses revealing a striking
      discrimination failure. Diverging inflammatory responses only occurred when
      Salmonella subsequently proliferated and induced escalating neutrophil
      infiltration, while harmless E. coli was rapidly cleared from the tissue and
      inflammation resolved. Transient intestinal inflammation induced by harmless E.
      coli tolerized against subsequent exposure thereby preventing chronic
      inflammation during repeated exposure. These data revealed a striking failure of
      the intestinal immune system to discriminate pathogens from harmless microbes
      based on distinct molecular signatures. Instead, appropriate intestinal responses
      to gut microbiota might be ensured by immediate inflammatory responses to any
      rise in microbial tissue loads, and desensitization after bacterial clearance.

PMID- 22586459
TI  - Evolving sensitivity balances Boolean Networks.
AB  - We investigate the sensitivity of Boolean Networks (BNs) to mutations. We are
      interested in Boolean Networks as a model of Gene Regulatory Networks (GRNs). We
      adopt Ribeiro and Kauffman's Ergodic Set and use it to study the long term
      dynamics of a BN. We define the sensitivity of a BN to be the mean change in its
      Ergodic Set structure under all possible loss of interaction mutations. In silico
      experiments were used to selectively evolve BNs for sensitivity to losing
      interactions. We find that maximum sensitivity was often achievable and resulted
      in the BNs becoming topologically balanced, i.e. they evolve towards network
      structures in which they have a similar number of inhibitory and excitatory
      interactions. In terms of the dynamics, the dominant sensitivity strategy that
      evolved was to build BNs with Ergodic Sets dominated by a single long limit cycle
      which is easily destabilised by mutations. We discuss the relevance of our
      findings in the context of Stem Cell Differentiation and propose a relationship
      between pluripotent stem cells and our evolved sensitive networks.

PMID- 22586460
TI  - Depletion of cellular pre-replication complex factors results in increased human
      cytomegalovirus DNA replication.
AB  - Although HCMV encodes many genes required for the replication of its DNA genome,
      no HCMV-encoded orthologue of the origin binding protein, which has been
      identified in other herpesviruses, has been identified. This has led to
      speculation that HCMV may use other viral proteins or possibly cellular factors
      for the initiation of DNA synthesis. It is also unclear whether cellular
      replication factors are required for efficient replication of viral DNA during or
      after viral replication origin recognition. Consequently, we have asked whether
      cellular pre-replication (pre-RC) factors that are either initially associated
      with cellular origin of replication (e.g. ORC2), those which recruit other
      replication factors (e.g. Cdt1 or Cdc6) or those which are subsequently recruited
      (e.g. MCMs) play any role in the HCMV DNA replication. We show that whilst RNAi
      mediated knock-down of these factors in the cell affects cellular DNA
      replication, as predicted, it results in concomitant increases in viral DNA
      replication. These data show that cellular factors which initiate cellular DNA
      synthesis are not required for the initiation of replication of viral DNA and
      suggest that inhibition of cellular DNA synthesis, in itself, fosters conditions
      which are conducive to viral DNA replication.

PMID- 22586461
TI  - Screening estrogenic activities of chemicals or mixtures in vivo using transgenic
      (cyp19a1b-GFP) zebrafish embryos.
AB  - The tg(cyp19a1b-GFP) transgenic zebrafish expresses GFP (green fluorescent
      protein) under the control of the cyp19a1b gene, encoding brain aromatase. This
      gene has two major characteristics: (i) it is only expressed in radial glial
      progenitors in the brain of fish and (ii) it is exquisitely sensitive to
      estrogens. Based on these properties, we demonstrate that natural or synthetic
      hormones (alone or in binary mixture), including androgens or progestagens, and
      industrial chemicals induce a concentration-dependent GFP expression in radial
      glial progenitors. As GFP expression can be quantified by in vivo imaging, this
      model presents a very powerful tool to screen and characterize compounds
      potentially acting as estrogen mimics either directly or after metabolization by
      the zebrafish embryo. This study also shows that radial glial cells that act as
      stem cells are direct targets for a large panel of endocrine disruptors, calling
      for more attention regarding the impact of environmental estrogens and/or certain
      pharmaceuticals on brain development. Altogether these data identify this in vivo
      bioassay as an interesting alternative to detect estrogen mimics in hazard and
      risk assessment perspective.

PMID- 22586462
TI  - 3D profile-based approach to proteome-wide discovery of novel human chemokines.
AB  - Chemokines are small secreted proteins with important roles in immune responses.
      They consist of a conserved three-dimensional (3D) structure, so-called IL8-like
      chemokine fold, which is supported by disulfide bridges characteristic of this
      protein family. Sequence- and profile-based computational methods have been
      proficient in discovering novel chemokines by making use of their sequence
      conserved cysteine patterns. However, it has been recently shown that some
      chemokines escaped annotation by these methods due to low sequence similarity to
      known chemokines and to different arrangement of cysteines in sequence and in 3D.
      Innovative methods overcoming the limitations of current techniques may allow the
      discovery of new remote homologs in the still functionally uncharacterized
      fraction of the human genome. We report a novel computational approach for
      proteome-wide identification of remote homologs of the chemokine family that uses
      fold recognition techniques in combination with a scaffold-based automatic
      mapping of disulfide bonds to define a 3D profile of the chemokine protein
      family. By applying our methodology to all currently uncharacterized human
      protein sequences, we have discovered two novel proteins that, without having
      significant sequence similarity to known chemokines or characteristic cysteine
      patterns, show strong structural resemblance to known anti-HIV chemokines.
      Detailed computational analysis and experimental structural investigations based
      on mass spectrometry and circular dichroism support our structural predictions
      and highlight several other chemokine-like features. The results obtained support
      their functional annotation as putative novel chemokines and encourage further
      experimental characterization. The identification of remote homologs of human
      chemokines may provide new insights into the molecular mechanisms causing
      pathologies such as cancer or AIDS, and may contribute to the development of
      novel treatments. Besides, the genome-wide applicability of our methodology based
      on 3D protein family profiles may open up new possibilities for improving and
      accelerating protein function annotation processes.

PMID- 22586463
TI  - Disruption of the Eng18B ENGase gene in the fungal biocontrol agent Trichoderma
      atroviride affects growth, conidiation and antagonistic ability.
AB  - The recently identified phylogenetic subgroup B5 of fungal glycoside hydrolase
      family 18 genes encodes enzymes with mannosyl glycoprotein endo-N-acetyl-beta-D
      glucosaminidase (ENGase)-type activity. Intracellular ENGase activity is
      associated with the endoplasmic reticulum associated protein degradation pathway
      (ERAD) of misfolded glycoproteins, although the biological relevance in
      filamentous fungi is not known. Trichoderma atroviride is a mycoparasitic fungus
      that is used for biological control of plant pathogenic fungi. The present work
      is a functional study of the T. atroviride B5-group gene Eng18B, with emphasis on
      its role in fungal growth and antagonism. A homology model of T. atroviride
      Eng18B structure predicts a typical glycoside hydrolase family 18 (alphabeta)(8)
      barrel architecture. Gene expression analysis shows that Eng18B is induced in
      dual cultures with the fungal plant pathogens Botrytis cinerea and Rhizoctonia
      solani, although a basal expression is observed in all growth conditions tested.
      Eng18B disruption strains had significantly reduced growth rates but higher
      conidiation rates compared to the wild-type strain. However, growth rates on
      abiotic stress media were significantly higher in Eng18B disruption strains
      compared to the wild-type strain. No difference in spore germination, germ-tube
      morphology or in hyphal branching was detected. Disruption strains produced less
      biomass in liquid cultures than the wild-type strain when grown with chitin as
      the sole carbon source. In addition, we determined that Eng18B is required for
      the antagonistic ability of T. atroviride against the grey mould fungus B.
      cinerea in dual cultures and that this reduction in antagonistic ability is
      partly connected to a secreted factor. The phenotypes were recovered by re
      introduction of an intact Eng18B gene fragment in mutant strains. A putative role
      of Eng18B ENGase activity in the endoplasmic reticulum associated protein
      degradation pathway of endogenous glycoproteins in T. atroviride is discussed in
      relation to the observed phenotypes.

PMID- 22586464
TI  - Call cultures in orang-utans?
AB  - BACKGROUND: Several studies suggested great ape cultures, arguing that human
      cumulative culture presumably evolved from such a foundation. These focused on
      conspicuous behaviours, and showed rich geographic variation, which could not be
      attributed to known ecological or genetic differences. Although geographic
      variation within call types (accents) has previously been reported for orang
      utans and other primate species, we examine geographic variation in the
      presence/absence of discrete call types (dialects). Because orang-utans have been
      shown to have geographic variation that is not completely explicable by genetic
      or ecological factors we hypothesized that this will be similar in the call
      domain and predict that discrete call type variation between populations will be
      found. METHODOLOGY/PRINCIPAL FINDINGS: We examined long-term behavioural data
      from five orang-utan populations and collected fecal samples for genetic
      analyses. We show that there is geographic variation in the presence of discrete
      types of calls. In exactly the same behavioural context (nest building and infant
      retrieval), individuals in different wild populations customarily emit either
      qualitatively different calls or calls in some but not in others. By comparing
      patterns in call-type and genetic similarity, we suggest that the observed
      variation is not likely to be explained by genetic or ecological differences.
      CONCLUSION/SIGNIFICANCE: These results are consistent with the potential presence
      of 'call cultures' and suggest that wild orang-utans possess the ability to
      invent arbitrary calls, which spread through social learning. These findings
      differ substantially from those that have been reported for primates before.
      First, the results reported here are on dialect and not on accent. Second, this
      study presents cases of production learning whereas most primate studies on vocal
      learning were cases of contextual learning. We conclude with speculating on how
      these findings might assist in bridging the gap between vocal communication in
      non-human primates and human speech.

PMID- 22586465
TI  - Proteome-wide analysis of single-nucleotide variations in the N-glycosylation
      sequon of human genes.
AB  - N-linked glycosylation is one of the most frequent post-translational
      modifications of proteins with a profound impact on their biological function.
      Besides other functions, N-linked glycosylation assists in protein folding,
      determines protein orientation at the cell surface, or protects proteins from
      proteases. The N-linked glycans attach to asparagines in the sequence context Asn
      X-Ser/Thr, where X is any amino acid except proline. Any variation (e.g. non
      synonymous single nucleotide polymorphism or mutation) that abolishes the N
      glycosylation sequence motif will lead to the loss of a glycosylation site. On
      the other hand, variations causing a substitution that creates a new N
      glycosylation sequence motif can result in the gain of glycosylation. Although
      the general importance of glycosylation is well known and acknowledged, the
      effect of variation on the actual glycoproteome of an organism is still mostly
      unknown. In this study, we focus on a comprehensive analysis of non-synonymous
      single nucleotide variations (nsSNV) that lead to either loss or gain of the N
      glycosylation motif. We find that 1091 proteins have modified N-glycosylation
      sequons due to nsSNVs in the genome. Based on analysis of proteins that have a
      solved 3D structure at the site of variation, we find that 48% of the variations
      that lead to changes in glycosylation sites occur at the loop and bend regions of
      the proteins. Pathway and function enrichment analysis show that a significant
      number of proteins that gained or lost the glycosylation motif are involved in
      kinase activity, immune response, and blood coagulation. A structure-function
      analysis of a blood coagulation protein, antithrombin III and a protease,
      cathepsin D, showcases how a comprehensive study followed by structural analysis
      can help better understand the functional impact of the nsSNVs.

PMID- 22586466
TI  - Overfeeding reduces insulin sensitivity and increases oxidative stress, without
      altering markers of mitochondrial content and function in humans.
AB  - BACKGROUND: Mitochondrial dysfunction and increased oxidative stress are
      associated with obesity and type 2 diabetes. High fat feeding induces insulin
      resistance and increases skeletal muscle oxidative stress in rodents, but there
      is controversy as to whether skeletal muscle mitochondrial biogenesis and
      function is altered. METHODOLOGY AND PRINCIPAL FINDINGS: Forty (37 +/- 2 y) non
      obese (25.6 +/- 0.6 kg/m(2)) sedentary men (n = 20) and women (n = 20) were
      overfed (+1040 +/- 100 kcal/day, 46 +/- 1% of energy from fat) for 28 days.
      Hyperinsulinemic-euglycemic clamps were performed at baseline and day 28 of
      overfeeding and skeletal muscle biopsies taken at baseline, day 3 and day 28 of
      overfeeding in a sub cohort of 26 individuals (13 men and 13 women) that
      consented to having all 3 biopsies performed. Weight increased on average in the
      whole cohort by 0.6 +/- 0.1 and 2.7 +/- 0.3 kg at days 3 and 28, respectively
      (P<0.0001, without a significant difference in the response between men and women
      (P = 0.4). Glucose infusion rate during the hyperinsulinemic-euglycemic clamp
      decreased from 54.8 +/- 2.8 at baseline to 50.3 +/- 2.5 umol/min/kg FFM at day 28
      of overfeeding (P = 0.03) without a significant difference between men and women
      (P = 0.4). Skeletal muscle protein carbonyls and urinary F2-isoprostanes
      increased with overfeeding (P<0.05). Protein levels of muscle peroxisome
      proliferator-activated receptor gamma coactivator-1alpha (PGC1alpha) and subunits
      from complex I, II and V of the electron transport chain were increased at day 3
      (all P<0.05) and returned to basal levels at day 28. No changes were detected in
      muscle citrate synthase activity or ex vivo CO(2) production at either time
      point. CONCLUSIONS: Peripheral insulin resistance was induced by overfeeding,
      without reducing any of the markers of mitochondrial content that were examined.
      Oxidative stress was however increased, and may have contributed to the reduction
      in insulin sensitivity observed.

PMID- 22586467
TI  - Impairment of the organization of locomotor and exploratory behaviors in bile
      duct-ligated rats.
AB  - Hepatic encephalopathy (HE) arises from acute or chronic liver diseases and leads
      to several problems, including motor impairment. Animal models of chronic liver
      disease have extensively investigated the mechanisms of this disease. Impairment
      of locomotor activity has been described in different rat models. However, these
      studies are controversial and the majority has primarily analyzed activity
      parameters. Therefore, the aim of the present study was to evaluate locomotor and
      exploratory behavior in bile duct-ligated (BDL) rats to explore the spatial and
      temporal structure of behavior. Adult female Wistar rats underwent common bile
      duct ligation (BDL rats) or the manipulation of common bile duct without ligation
      (control rats). Six weeks after surgery, control and BDL rats underwent open
      field, plus-maze and foot-fault behavioral tasks. The BDL rats developed chronic
      liver failure and exhibited a decrease in total distance traveled, increased
      total immobility time, smaller number of rearings, longer periods in the home
      base area and decreased percentage of time in the center zone of the arena, when
      compared to the control rats. Moreover, the performance of the BDL rats was not
      different from the control rats for the elevated plus-maze and foot-fault tasks.
      Therefore, the BDL rats demonstrated disturbed spontaneous locomotor and
      exploratory activities as a consequence of altered spatio-temporal organization
      of behavior.

PMID- 22586468
TI  - Sodium selenide toxicity is mediated by O2-dependent DNA breaks.
AB  - Hydrogen selenide is a recurrent metabolite of selenium compounds. However, few
      experiments studied the direct link between this toxic agent and cell death. To
      address this question, we first screened a systematic collection of Saccharomyces
      cerevisiae haploid knockout strains for sensitivity to sodium selenide, a donor
      for hydrogen selenide (H(2)Se/HSe(-/)Se(2-)). Among the genes whose deletion
      caused hypersensitivity, homologous recombination and DNA damage checkpoint genes
      were over-represented, suggesting that DNA double-strand breaks are a dominant
      cause of hydrogen selenide toxicity. Consistent with this hypothesis, treatment
      of S. cerevisiae cells with sodium selenide triggered G2/M checkpoint activation
      and induced in vivo chromosome fragmentation. In vitro, sodium selenide directly
      induced DNA phosphodiester-bond breaks via an O(2)-dependent reaction. The
      reaction was inhibited by mannitol, a hydroxyl radical quencher, but not by
      superoxide dismutase or catalase, strongly suggesting the involvement of hydroxyl
      radicals and ruling out participations of superoxide anions or hydrogen peroxide.
      The (*)OH signature could indeed be detected by electron spin resonance upon
      exposure of a solution of sodium selenide to O(2). Finally we showed that, in
      vivo, toxicity strictly depended on the presence of O(2). Therefore, by combining
      genome-wide and biochemical approaches, we demonstrated that, in yeast cells,
      hydrogen selenide induces toxic DNA breaks through an O(2)-dependent radical
      based mechanism.

PMID- 22586469
TI  - Gene mapping via bulked segregant RNA-Seq (BSR-Seq).
AB  - Bulked segregant analysis (BSA) is an efficient method to rapidly and efficiently
      map genes responsible for mutant phenotypes. BSA requires access to quantitative
      genetic markers that are polymorphic in the mapping population. We have developed
      a modification of BSA (BSR-Seq) that makes use of RNA-Seq reads to efficiently
      map genes even in populations for which no polymorphic markers have been
      previously identified. Because of the digital nature of next-generation
      sequencing (NGS) data, it is possible to conduct de novo SNP discovery and
      quantitatively genotype BSA samples by analyzing the same RNA-Seq data using an
      empirical Bayesian approach. In addition, analysis of the RNA-Seq data provides
      information on the effects of the mutant on global patterns of gene expression at
      no extra cost. In combination these results greatly simplify gene cloning
      experiments. To demonstrate the utility of this strategy BSR-Seq was used to
      clone the glossy3 (gl3) gene of maize. Mutants of the glossy loci exhibit altered
      accumulation of epicuticular waxes on juvenile leaves. By subjecting the
      reference allele of gl3 to BSR-Seq, we were able to map the gl3 locus to an ~ 2
      Mb interval. The single gene located in the ~ 2 Mb mapping interval whose
      expression was down-regulated in the mutant pool was subsequently demonstrated to
      be the gl3 gene via the analysis of multiple independent transposon induced
      mutant alleles. The gl3 gene encodes a putative myb transcription factor, which
      directly or indirectly affects the expression of a number of genes involved in
      the biosynthesis of very-long-chain fatty acids.

PMID- 22586470
TI  - Hepcidin expression in iron overload diseases is variably modulated by
      circulating factors.
AB  - Hepcidin is a regulatory hormone that plays a major role in controlling body iron
      homeostasis. Circulating factors (holotransferrin, cytokines, erythroid
      regulators) might variably contribute to hepcidin modulation in different
      pathological conditions. There are few studies analysing the relationship between
      hepcidin transcript and related protein expression profiles in humans. Our aims
      were: a. to measure hepcidin expression at either hepatic, serum and urinary
      level in three paradigmatic iron overload conditions (hemochromatosis,
      thalassemia and dysmetabolic iron overload syndrome) and in controls; b. to
      measure mRNA hepcidin expression in two different hepatic cell lines (HepG2 and
      Huh-7) exposed to patients and controls sera to assess whether circulating
      factors could influence hepcidin transcription in different pathological
      conditions. Our findings suggest that hepcidin assays reflect hepatic hepcidin
      production, but also indicate that correlation is not ideal, likely due to
      methodological limits and to several post-trascriptional events. In vitro study
      showed that THAL sera down-regulated, HFE-HH and C-NAFLD sera up-regulated
      hepcidin synthesis. HAMP mRNA expression in Huh-7 cells exposed to sera form C
      Donors, HFE-HH and THAL reproduced, at lower level, the results observed in
      HepG2, suggesting the important but not critical role of HFE in hepcidin
      regulation.

PMID- 22586471
TI  - Patrilineal perspective on the Austronesian diffusion in Mainland Southeast Asia.
AB  - The Cham people are the major Austronesian speakers of Mainland Southeast Asia
      (MSEA) and the reconstruction of the Cham population history can provide insights
      into their diffusion. In this study, we analyzed non-recombining region of the Y
      chromosome markers of 177 unrelated males from four populations in MSEA,
      including 59 Cham, 76 Kinh, 25 Lao, and 17 Thai individuals. Incorporating
      published data from mitochondrial DNA (mtDNA), our results indicated that, in
      general, the Chams are an indigenous Southeast Asian population. The origin of
      the Cham people involves the genetic admixture of the Austronesian immigrants
      from Island Southeast Asia (ISEA) with the local populations in MSEA. Discordance
      between the overall patterns of Y chromosome and mtDNA in the Chams is evidenced
      by the presence of some Y chromosome lineages that prevail in South Asians. Our
      results suggest that male-mediated dispersals via the spread of religions and
      business trade might play an important role in shaping the patrilineal gene pool
      of the Cham people.

PMID- 22586472
TI  - Exploiting temporal network structures of human interaction to effectively
      immunize populations.
AB  - Decreasing the number of people who must be vaccinated to immunize a community
      against an infectious disease could both save resources and decrease outbreak
      sizes. A key to reaching such a lower threshold of immunization is to find and
      vaccinate people who, through their behavior, are more likely than average to
      become infected and to spread the disease further. Fortunately, the very behavior
      that makes these people important to vaccinate can help us to localize them.
      Earlier studies have shown that one can use previous contacts to find people that
      are central in static contact networks. However, real contact patterns are not
      static. In this paper, we investigate if there is additional information in the
      temporal contact structure for vaccination protocols to exploit. We answer this
      affirmative by proposing two immunization methods that exploit temporal
      correlations and showing that these methods outperform a benchmark static-network
      protocol in four empirical contact datasets under various epidemic scenarios.
      Both methods rely only on obtainable, local information, and can be implemented
      in practice. For the datasets directly related to contact patterns of potential
      disease spreading (of sexually-transmitted and nosocomial infections
      respectively), the most efficient protocol is to sample people at random and
      vaccinate their latest contacts. The network datasets are temporal, which enables
      us to make more realistic evaluations than earlier studies--we use only
      information about the past for the purpose of vaccination, and about the future
      to simulate disease outbreaks. Using analytically tractable models, we identify
      two temporal structures that explain how the protocols earn their efficiency in
      the empirical data. This paper is a first step towards real vaccination protocols
      that exploit temporal-network structure--future work is needed both to
      characterize the structure of real contact sequences and to devise immunization
      methods that exploit these.

PMID- 22586473
TI  - Control of germline stem cell division frequency--a novel, developmentally
      regulated role for epidermal growth factor signaling.
AB  - Exploring adult stem cell dynamics in normal and disease states is crucial to
      both better understanding their in vivo role and better realizing their
      therapeutic potential. Here we address the division frequency of Germline Stem
      Cells (GSCs) in testes of Drosophila melanogaster. We show that GSC division
      frequency is under genetic control of the highly conserved Epidermal Growth
      Factor (EGF) signaling pathway. When EGF signaling was attenuated, we detected a
      two-fold increase in the percentage of GSCs in mitotic division compared to GSCs
      in control animals. Ex vivo and in vivo experiments using a marker for cells in S
      phase of the cell cycle showed that the GSCs in EGF mutant testes divide faster
      than GSCs in control testes. The increased mitotic activity of GSCs in EGF
      mutants was rescued by restoring EGF signaling in the GSCs, and reproduced in
      testes from animals with soma-depleted EGF-Receptor (EGFR). Interestingly, EGF
      attenuation specifically increased the GSC division frequency in adult testes,
      but not in larval testes. Furthermore, GSCs in testes with tumors resulting from
      the perturbation of other conserved signaling pathways divided at normal
      frequencies. We conclude that EGF signaling from the GSCs to the CySCs normally
      regulates GSC division frequency. The EGF signaling pathway is bifurcated and
      acts differently in adult compared to larval testes. In addition, regulation of
      GSC division frequency is a specific role for EGF signaling as it is not affected
      in all tumor models. These data advance our understanding concerning stem cell
      dynamics in normal tissues and in a tumor model.

PMID- 22586474
TI  - Phylogenetic codivergence supports coevolution of mimetic Heliconius butterflies.
AB  - The unpalatable and warning-patterned butterflies Heliconius erato and Heliconius
      melpomene provide the best studied example of mutualistic Mullerian mimicry,
      thought-but rarely demonstrated-to promote coevolution. Some of the strongest
      available evidence for coevolution comes from phylogenetic codivergence, the
      parallel divergence of ecologically associated lineages. Early evolutionary
      reconstructions suggested codivergence between mimetic populations of H. erato
      and H. melpomene, and this was initially hailed as one of the most striking known
      cases of coevolution. However, subsequent molecular phylogenetic analyses found
      discrepancies in phylogenetic branching patterns and timing (topological and
      temporal incongruence) that argued against codivergence. We present the first
      explicit cophylogenetic test of codivergence between mimetic populations of H.
      erato and H. melpomene, and re-examine the timing of these radiations. We find
      statistically significant topological congruence between multilocus coalescent
      population phylogenies of H. erato and H. melpomene. Cophylogenetic historical
      reconstructions support repeated codivergence of mimetic populations, from the
      base of the sampled radiations. Pairwise distance correlation tests, based on our
      coalescent analyses plus recently published AFLP and wing colour pattern gene
      data, also suggest that the phylogenies of H. erato and H. melpomene show
      significant topological congruence. Divergence time estimates, based on a
      Bayesian coalescent model, suggest that the evolutionary radiations of H. erato
      and H. melpomene occurred over the same time period, and are compatible with a
      series of temporally congruent codivergence events. Our results suggest that
      differences in within-species genetic divergence are the result of a greater
      overall effective population size for H. erato relative to H. melpomene and do
      not imply incongruence in the timing of their phylogenetic radiations. Repeated
      codivergence between Mullerian co-mimics, predicted to exert mutual selection
      pressures, strongly suggests coevolution. Our results therefore support a history
      of reciprocal coevolution between Mullerian co-mimics characterised by
      phylogenetic codivergence and parallel phenotypic change.

PMID- 22586475
TI  - Cell expansion-mediated organ growth is affected by mutations in three EXIGUA
      genes.
AB  - Organ growth depends on two distinct, yet integrated, processes: cell
      proliferation and post-mitotic cell expansion. Although the regulatory networks
      of plant cell proliferation during organ growth have begun to be unveiled, the
      mechanisms regulating post-mitotic cell growth remain mostly unknown. Here, we
      report the characterization of three EXIGUA (EXI) genes that encode different
      subunits of the cellulose synthase complex specifically required for secondary
      cell wall formation. Despite this highly specific role of EXI genes, all the
      cells within the leaf, even those that do not have secondary walls, display small
      sizes in the exi mutants. In addition, we found a positive correlation between
      cell size and the DNA ploidy levels in exi mutant leaves, suggesting that both
      processes share some regulatory components. Our results are consistent with the
      hypothesis that the collapsed xylem vessels of the exi mutants hamper water
      transport throughout the plant, which, in turn, limits the turgor pressure levels
      required for normal post-mitotic cell expansion during leaf growth.

PMID- 22586476
TI  - Programmatic impact of QuantiFERON-TB Gold In-Tube implementation on latent
      tuberculosis diagnosis and treatment in a public health clinic.
AB  - BACKGROUND: QuantiFERON-TB Gold In-Tube (QFT-GIT) is considered an alternative to
      the tuberculin skin test (TST) for the diagnosis of tuberculosis (TB) infection,
      but the programmatic impact of QFT-GIT implementation is largely unknown. In
      March, 2010, the Baltimore City Health Department (BCHD) introduced routine QFT
      GIT testing for individuals referred to the TB program for suspected latent TB
      infection (LTBI). DESIGN: Retrospective study comparing LTBI diagnosis and
      treatment during the 13 months before and after QFT-GIT implementation at the
      BCHD TB clinic. RESULTS: 607 and 750 individuals were referred by community
      providers for suspected LTBI in the pre- and post-QFT-GIT periods, respectively.
      Most individuals in the pre- and post-QFT-GIT periods were referred on the basis
      of a positive TST (597/607 [98%] vs. 690/750 [92%], respectively) and were
      foreign-born (363/607[59%] vs. 507/750[68%], respectively). BCHD performed QFT
      GIT testing for 375/543 (69%) eligible individuals in the post-QFT-GIT period, of
      which 185 (49%) were positive, 178 (47%) were negative, 1 (0.25%) was
      indeterminate, and 11 (3%) did not yield results. Concordance of QFT-GIT with TST
      was low (183/352[52%]). Foreign-born individuals had higher proportions of QFT
      GIT positivity (57%) than US-born individuals (36%; AOR 3.3 [95%CI 1.7-6.2]).
      Significantly fewer individuals received a final diagnosis of LTBI in the post
      QFT-GIT period (397/567 [70%]) compared to the pre-QFT-GIT period (445/452 [98%],
      p<0.001). In the post-QFT-GIT period, only 230/399 (58%) of those receiving QFT
      GIT testing had a final diagnosis of LTBI, while 167/168 (99%) of those without
      QFT-GIT testing were diagnosed with LTBI (p<0.001). There was no difference in
      treatment initiation between those with and without QFT-GIT testing (175/230
      [76%]) vs. 133/167 [80%], respectively) in the post-QFT-GIT period. CONCLUSION:
      QFT-GIT implementation for LTBI evaluation in a public health clinic
      significantly reduced the proportion of referred individuals in whom LTBI was
      diagnosed. QFT-GIT testing had no impact on treatment initiation or completion
      among those diagnosed with LTBI.

PMID- 22586477
TI  - Fall classification by machine learning using mobile phones.
AB  - Fall prevention is a critical component of health care; falls are a common source
      of injury in the elderly and are associated with significant levels of mortality
      and morbidity. Automatically detecting falls can allow rapid response to
      potential emergencies; in addition, knowing the cause or manner of a fall can be
      beneficial for prevention studies or a more tailored emergency response. The
      purpose of this study is to demonstrate techniques to not only reliably detect a
      fall but also to automatically classify the type. We asked 15 subjects to
      simulate four different types of falls-left and right lateral, forward trips, and
      backward slips-while wearing mobile phones and previously validated, dedicated
      accelerometers. Nine subjects also wore the devices for ten days, to provide data
      for comparison with the simulated falls. We applied five machine learning
      classifiers to a large time-series feature set to detect falls. Support vector
      machines and regularized logistic regression were able to identify a fall with
      98% accuracy and classify the type of fall with 99% accuracy. This work
      demonstrates how current machine learning approaches can simplify data collection
      for prevention in fall-related research as well as improve rapid response to
      potential injuries due to falls.

PMID- 22586479
TI  - Fussy feeders: phyllosoma larvae of the Western Rocklobster (Panulirus cygnus)
      demonstrate prey preference.
AB  - The Western Rocklobster (Panulirus cygnus) is the most valuable single species
      fishery in Australia and the largest single country spiny lobster fishery in the
      world. In recent years a well-known relationship between oceanographic conditions
      and lobster recruitment has become uncoupled, with significantly lower
      recruitment than expected, generating interest in the factors influencing
      survival and development of the planktonic larval stages. The nutritional
      requirements and wild prey of the planktotrophic larval stage (phyllosoma) of P.
      cygnus were previously unknown, hampering both management and aquaculture efforts
      for this species. Ship-board feeding trials of wild-caught mid-late stage P.
      cygnus phyllosoma in the eastern Indian Ocean, off the coast of Western
      Australia, were conducted in July 2010 and August-September 2011. In a series of
      experiments, phyllosoma were fed single and mixed species diets of relatively
      abundant potential prey items (chaetognaths, salps, and krill). Chaetognaths were
      consumed in 2-8 times higher numbers than the other prey, and the rate of
      consumption of chaetognaths increased with increasing concentration of prey. The
      highly variable lipid content of the phyllosoma, and the fatty acid profiles of
      the phyllosoma and chaetognaths, indicated they were from an oligotrophic oceanic
      food chain where food resources for macrozooplankton were likely to be
      constrained. Phyllosoma fed chaetognaths over 6 days showed significant changes
      in some fatty acids and tended to accumulate lipid, indicating an improvement in
      overall nutritional condition. The discovery of a preferred prey for P. cygnus
      will provide a basis for future oceanographic, management and aquaculture
      research for this economically and ecologically valuable species.

PMID- 22586478
TI  - Musical training induces functional plasticity in perceptual and motor networks:
      insights from resting-state FMRI.
AB  - A number of previous studies have examined music-related plasticity in terms of
      multi-sensory and motor integration but little is known about the functional and
      effective connectivity patterns of spontaneous intrinsic activity in these
      systems during the resting state in musicians. Using functional connectivity and
      Granger causal analysis, functional and effective connectivity among the motor
      and multi-sensory (visual, auditory and somatosensory) cortices were evaluated
      using resting-state functional magnetic resonance imaging (fMRI) in musicians and
      non-musicians. The results revealed that functional connectivity was
      significantly increased in the motor and multi-sensory cortices of musicians.
      Moreover, the Granger causality results demonstrated a significant increase
      outflow-inflow degree in the auditory cortex with the strongest causal outflow
      pattern of effective connectivity being found in musicians. These resting state
      fMRI findings indicate enhanced functional integration among the lower-level
      perceptual and motor networks in musicians, and may reflect functional
      consolidation (plasticity) resulting from long-term musical training, involving
      both multi-sensory and motor functional integration.

PMID- 22586480
TI  - Surveillance length and validity of benchmarks for central line-associated
      bloodstream infection incidence rates in intensive care units.
AB  - INTRODUCTION: Several national and regional central line-associated bloodstream
      infections (CLABSI) surveillance programs do not require continuous hospital
      participation. We evaluated the effect of different hospital participation
      requirements on the validity of annual CLABSI incidence rate benchmarks for
      intensive care units (ICUs). METHODS: We estimated the annual pooled CLABSI
      incidence rates for both a real regional (<100 ICUs) and a simulated national
      (600 ICUs) surveillance program, which were used as a reference for the
      simulations. We simulated scenarios where the annual surveillance participation
      was randomly or non-randomly reduced. Each scenario's annual pooled CLABSI
      incidence rate was estimated and compared to the reference rates in terms of
      validity, bias, and proportion of simulation iterations that presented valid
      estimates (ideal if >= 90%). RESULTS: All random scenarios generated valid CLABSI
      incidence rates estimates (bias -0.37 to 0.07 CLABSI/1000 CVC-days), while non
      random scenarios presented a wide range of valid estimates (0 to 100%) and higher
      bias (-2.18 to 1.27 CLABSI/1000 CVC-days). In random scenarios, the higher the
      number of participating ICUs, the shorter the participation required to generate
      >= 90% valid replicates. While participation requirements in a countrywide
      program ranged from 3 to 13 surveillance blocks (1 block = 28 days), requirements
      for a regional program ranged from 9 to 13 blocks. CONCLUSIONS: Based on the
      results of our model of national CLABSI reporting, the shortening of
      participation requirements may be suitable for nationwide ICU CLABSI surveillance
      programs if participation months are randomly chosen. However, our regional
      models showed that regional programs should opt for continuous participation to
      avoid biased benchmarks.

PMID- 22586481
TI  - Interleukin-7 influences FOXP3+CD4+ regulatory T cells peripheral homeostasis.
AB  - Mechanisms governing peripheral CD4+ FOXP3+ regulatory T cells (Treg) survival
      and homeostasis are multiple suggesting tight and complex regulation of
      regulatory T cells homeostasis. Some specific factors, such as TGF-beta,
      interleukin-2 (IL-2) and B7 costimulatory molecules have been identified as
      essentials for maintenance of the peripheral Treg compartment. Conversely, Treg
      dependency upon classical T cell homeostatic factors such as IL-7 is still
      unclear. In this work, we formally investigated the role of IL-7 in Treg
      homeostasis in vivo in murine models. We demonstrated that IL-7 availability
      regulated the size of peripheral Treg cell pool and thus paralleled the impact of
      IL-7 on conventional T cell pool. Moreover, we showed that IL-7 administration
      increased Treg cell numbers by inducing thymic-independent Treg peripheral
      expansion. Importantly the impact of IL-7 on Treg expansion was detected whether
      conventional T cells were present or absent as IL-7 directly participates to the
      peripheral expansion of Treg after adoptive transfer into lymphopenic hosts. Our
      results definitively identify IL-7 as a central factor contributing to Treg
      peripheral homeostasis, thus reassembling Treg to other T cell subsets in respect
      of their need for IL-7 for their peripheral maintenance.

PMID- 22586482
TI  - Catheter colonization and abscess formation due to Staphylococcus epidermidis
      with normal and small-colony-variant phenotype is mouse strain dependent.
AB  - Coagulase-negative staphylococci (CoNS) form a thick, multilayered biofilm on
      foreign bodies and are a major cause of nosocomial implant-associated infections.
      Although foreign body infection models are well-established, limited in vivo data
      are available for CoNS with small-colony-variant (SCV) phenotype described as
      causative agents in implant-associated infections. Therefore, we investigated the
      impact of the Staphylococcus epidermidis phenotype on colonization of implanted
      PVC catheters and abscess formation in three different mouse strains. Following
      introduction of a catheter subcutaneously in each flank of 8- to 12-week-old
      inbred C57BL/6JCrl (B6J), outbred Crl:CD1(ICR) (CD-1), and inbred BALB/cAnNCrl
      (BALB/c) male mice, doses of S. epidermidis O-47 wild type, its hemB mutant with
      stable SCV phenotype, or its complemented mutant at concentrations of 10(6) to
      10(9) colony forming units (CFUs) were gently spread onto each catheter. On day
      7, mice were sacrificed and the size of the abscesses as well as bacterial
      colonization was determined. A total of 11,500 CFUs of the complemented mutant
      adhered to the catheter in BALB/c followed by 9,960 CFUs and 9,900 CFUs from S.
      epidermidis wild type in BALB/c and CD-1, respectively. SCV colonization was
      highest in CD-1 with 9,500 CFUs, whereas SCVs were not detected in B6J. The
      minimum dose that led to colonization or abscess formation in all mouse strains
      was 10(7) or 10(8) CFUs of the normal phenotype, respectively. A minimum dose of
      10(8) or 10(9) CFU of the hemB mutant with stable SCV phenotype led to
      colonization only or abscess formation, respectively. The largest abscesses were
      detected in BALB/c inoculated with wild type bacteria or SCV (64 mm(2) vs. 28
      mm(2)). Our results indicate that colonization and abscess formation by different
      phenotypes of S. epidermidis in a foreign body infection model is most effective
      in inbred BALB/c followed by outbred CD-1 and inbred B6J mice.

PMID- 22586483
TI  - A prospective randomized controlled trial of the effects of vitamin D
      supplementation on cardiovascular disease risk.
AB  - Vitamin D (VitD) supplementation has been advocated for cardiovascular risk
      reduction; however, supporting data are sparse. The objective of this study was
      to determine whether VitD supplementation reduces cardiovascular risk. Subjects
      in this prospective, randomized, double-blind, placebo-controlled trial of post
      menopausal women with serum 25-hydroxyvitamin D concentrations >10 and <60 ng/mL
      were randomized to Vitamin D3 2500 IU or placebo, daily for 4 months. Primary
      endpoints were changes in brachial artery flow-mediated vasodilation (FMD),
      carotid-femoral pulse wave velocity (PWV), and aortic augmentation index (AIx).
      The 114 subjects were mean (standard deviation) 63.9 (3.0) years old with a 25
      hydroxyvitamin D level of 31.3 (10.6) ng/mL. Low VitD (<30 ng/mL) was present in
      47% and was associated with higher body-mass index, systolic blood pressure,
      glucose, CRP, and lower FMD (all p<0.05). After 4 months, 25-hydroxyvitamin D
      levels increased by 15.7 (9.3) ng/mL on vitamin D3 vs. -0.2 (6.1) ng/mL on
      placebo (p<0.001). There were no significant differences between groups in
      changes in FMD (0.3 [3.4] vs. 0.3 [2.6] %, p = 0.77), PWV (0.00 [1.06] vs. 0.05
      [0.92] m/s, p = 0.65), AIx (2.7 [6.3] vs. 0.9 [5.6] %, p = 0.10), or CRP (0.3
      [1.9] vs. 0.3 [4.2] mg/L, p = 0.97). Multivariable models showed no significant
      interactions between treatment group and low VitD status (<30 ng/mL) for changes
      in FMD (p = 0.65), PWV (p = 0.93), AIx (p = 0.97), or CRP (p = 0.26). In
      conclusion, VitD supplementation did not improve endothelial function, arterial
      stiffness, or inflammation. These observations do not support use of VitD
      supplementation to reduce cardiovascular disease risk.

PMID- 22586484
TI  - KRAS, BRAF and PIK3CA mutations and the loss of PTEN expression in Chinese
      patients with colorectal cancer.
AB  - BACKGROUND: To investigate the frequency and relationship of the KRAS, BRAF and
      PIK3CA mutations and the loss of PTEN expression in Chinese patients with
      colorectal cancer (CRC). METHODOLOGY/PRINCIPAL FINDINGS: Genomic DNA was
      extracted from the formalin-fixed paraffin-embedded (FFPE) tissues of 69 patients
      with histologically confirmed CRC. Automated sequencing analysis was conducted to
      detect mutations in the KRAS (codons 12, 13, and 14), BRAF (codon 600) and PIK3CA
      (codons 542, 545 and 1047). PTEN protein expression was evaluated by
      immunohistochemistry on 3 mm FFPE tissue sections. Statistical analysis was
      carried out using SPSS 16.0 software. The frequency of KRAS, BRAF and PIK3CA
      mutations and loss of PTEN expression was 43.9% (25/57), 25.4% (15/59), 8.2%
      (5/61) and 47.8% (33/69), respectively. The most frequent mutation in KRAS, BRAF
      and PIK3CA was V14G (26.7% of all mutations), V600E (40.0% of all mutations) and
      V600L (40.0% of all mutations), and H1047L (80.0% of all mutations),
      respectively. Six KRAS mutant patients (24.0%) harbored BRAF mutations. BRAF and
      PIK3CA mutations were mutually exclusive. No significant correlation was observed
      between the four biomarkers and patients' characteristics.
      CONCLUSIONS/SIGNIFICANCE: BRAF mutation rate is much higher in this study than in
      other studies, and overlap a lot with KRAS mutations. Besides, the specific types
      of KRAS and PIK3CA mutations in Chinese patients could be quite different from
      that of patients in other countries. Further studies are warranted to examine
      their impact on prognosis and response to targeted treatment.

PMID- 22586485
TI  - The prevalence of immunologic injury in renal allograft recipients with de novo
      proteinuria.
AB  - Post-transplant proteinuria is a common complication after renal transplantation;
      it is associated with reduced graft and recipient survival. However, the
      prevalence of histological causes has been reported with considerable variation.
      A clinico-pathological re-evaluation of post-transplant proteinuria is necessary,
      especially after dismissal of the term "chronic allograft nephropathy," which had
      been considered to be an important cause of proteinuria. Moreover, urinary
      protein can promote interstitial inflammation in native kidney, whether this
      occurs in renal allograft remains unknown. Factors that affect the graft outcome
      in patients with proteinuria also remain unclear. Here we collected 98 cases of
      renal allograft recipients who developed proteinuria after transplant,
      histological features were characterized using Banff scoring system. Cox
      proportional hazard regression models were used for graft survival predictors. We
      found that transplant glomerulopathy was the leading (40.8%) cause of post
      transplant proteinuria. Immunological causes, including transplant
      glomerulopathy, acute rejection, and chronic rejection accounted for the majority
      of all pathological causes of proteinuria. Nevertheless, almost all patients that
      developed proteinuria had immunological lesions in the graft, especially for
      interstitial inflammation. Intraglomerular C3 deposition was unexpectedly
      correlated with the severity of proteinuria. Moreover, the severity of
      interstitial inflammation was an independent risk factor for graft loss, while
      high level of hemoglobin was a protective factor for graft survival. This study
      revealed a predominance of immunological parameters in renal allografts with post
      transplant proteinuria. These parameters not only correlate with the severity of
      proteinuria, but also with the outcome of the graft.

PMID- 22586486
TI  - Echovirus 30 induced neuronal cell death through TRIO-RhoA signaling activation.
AB  - BACKGROUND: Echovirus 30 (Echo30) is one of the most frequently identified human
      enteroviruses (EVs) causing aseptic meningitis and encephalitis. However the
      mechanism underlying the pathogenesis of Echo30 infection with significant
      clinical outcomes is not completely understood. The aim of this investigation is
      to illustrate molecular pathologic alteration in neuronal cells induced by Echo30
      infection using clinical isolate from young patient with neurologic involvement.
      METHODOLOGY/PRINCIPAL FINDINGS: To characterize the neuronal cellular response to
      Echo30 infection, we performed a proteomic analysis based on two-dimensional gel
      electrophoresis (2-DE) and MALDI-TOF/TOF Mass Spectrophotometric (MS) analysis.
      We identified significant alteration of several protein expression levels in
      Echo30-infected SK-N-SH cells. Among these proteins, we focused on an outstanding
      up-regulation of Triple functional domain (TRIO) in Echo30-infected SK-N-SH
      cells. Generally, TRIO acts as a key component in the regulation of axon guidance
      and cell migration. In this study, we determined that TRIO plays a role in the
      novel pathways in Echo30 induced neuronal cell death. CONCLUSIONS/SIGNIFICANCE:
      Our finding shows that TRIO plays a critical role in neuronal cell death by
      Echo30 infection. Echo30 infection activates TRIO-guanine nucleotide exchange
      factor (GEF) domains (GEFD2) and RhoA signaling in turn. These results suggest
      that Echo30 infection induced neuronal cell death by activation of the TRIO-RhoA
      signaling. We expect the regulation of TRIO-RhoA signaling may represent a new
      therapeutic approach in treating aseptic meningitis and encephalitis induced by
      Echo30.

PMID- 22586487
TI  - Objective and self-rated sedentary time and indicators of metabolic health in
      Dutch and Hungarian 10-12 year olds: the ENERGY-Project.
AB  - BACKGROUND: The association between objectively assessed sedentary time and
      metabolic risk factors in childhood have rarely been studied. Therefore, we
      examined the independent relationship between objectively assessed and self-rated
      sedentary time and indicators of metabolic health in Dutch and Hungarian 10-12
      year olds. METHODOLOGY/PRINCIPAL FINDINGS: We performed a cross-sectional survey
      in primary schools. Participants were Dutch and Hungarian girls (n = 73, aged
      12.2 +/- 0.6 years, 18% overweight/obese) and boys (n = 69, aged 12.2 +/- 0.7
      years, 38% overweight/obese). Sedentary time and physical activity were assessed
      by the Actigraph accelerometer. TV and PC time were assessed by self-report.
      Adiposity indicators included body weight, height, and waist circumference (WC).
      Fasting plasma glucose, C-peptide, total cholesterol, low density lipoprotein
      cholesterol, high density lipoprotein cholesterol, and triglycerides were
      determined in capillary blood and summed into a metabolic risk score. Linear
      regression analyses were adjusted for physical activity, number of sedentary
      bouts and WC. Children spent on average 7.6 hours of their daily waking time in
      sedentary behavior and self-reported 116 +/- 64 min/day watching TV and 85 +/- 57
      min/day using the computer. Comparing the 1(st) and 4(th) quartile of objectively
      assessed sedentary time, C-Peptide levels, WC and BMI were significantly higher
      in the most sedentary quartile, while the difference in metabolic risk score was
      borderline significant (p = 0.09). Comparing the 1(st) and 4(th) quartile of TV
      time, BMI was significantly higher in the most sedentary quartile, while the
      difference in WC score was borderline significant (p = 0.06). In the adjusted
      linear regression analysis we found no significant association of sedentary time
      with metabolic risk. CONCLUSIONS/SIGNIFICANCE: Although BMI and WC were higher in
      the most sedentary versus the least sedentary children; we found no further
      evidence that more sedentary children were at increased metabolic risk.

PMID- 22586488
TI  - A two-stage random forest-based pathway analysis method.
AB  - Pathway analysis provides a powerful approach for identifying the joint effect of
      genes grouped into biologically-based pathways on disease. Pathway analysis is
      also an attractive approach for a secondary analysis of genome-wide association
      study (GWAS) data that may still yield new results from these valuable datasets.
      Most of the current pathway analysis methods focused on testing the cumulative
      main effects of genes in a pathway. However, for complex diseases, gene-gene
      interactions are expected to play a critical role in disease etiology. We
      extended a random forest-based method for pathway analysis by incorporating a two
      stage design. We used simulations to verify that the proposed method has the
      correct type I error rates. We also used simulations to show that the method is
      more powerful than the original random forest-based pathway approach and the set
      based test implemented in PLINK in the presence of gene-gene interactions.
      Finally, we applied the method to a breast cancer GWAS dataset and a lung cancer
      GWAS dataset and interesting pathways were identified that have implications for
      breast and lung cancers.

PMID- 22586489
TI  - Regeneration of pancreatic non-beta endocrine cells in adult mice following a
      single diabetes-inducing dose of streptozotocin.
AB  - The non-beta endocrine cells in pancreatic islets play an essential counterpart
      and regulatory role to the insulin-producing beta-cells in the regulation of
      blood-glucose homeostasis. While significant progress has been made towards the
      understanding of beta-cell regeneration in adults, very little is known about the
      regeneration of the non-beta endocrine cells such as glucagon-producing alpha
      cells and somatostatin producing delta-cells. Previous studies have noted the
      increase of alpha-cell composition in diabetes patients and in animal models. It
      is thus our hypothesis that non-beta-cells such as alpha-cells and delta-cells in
      adults can regenerate, and that the regeneration accelerates in diabetic
      conditions. To test this hypothesis, we examined islet cell composition in a
      streptozotocin (STZ)-induced diabetes mouse model in detail. Our data showed the
      number of alpha-cells in each islet increased following STZ-mediated beta-cell
      destruction, peaked at Day 6, which was about 3 times that of normal islets. In
      addition, we found delta-cell numbers doubled by Day 6 following STZ treatment.
      These data suggest alpha- and delta-cell regeneration occurred rapidly following
      a single diabetes-inducing dose of STZ in mice. Using in vivo BrdU labeling
      techniques, we demonstrated alpha- and delta-cell regeneration involved cell
      proliferation. Co-staining of the islets with the proliferating cell marker Ki67
      showed alpha- and delta-cells could replicate, suggesting self-duplication played
      a role in their regeneration. Furthermore, Pdx1(+)/Insulin(-) cells were detected
      following STZ treatment, indicating the involvement of endocrine progenitor cells
      in the regeneration of these non-beta cells. This is further confirmed by the
      detection of Pdx1(+)/glucagon(+) cells and Pdx1(+)/somatostatin(+) cells
      following STZ treatment. Taken together, our study demonstrated adult alpha- and
      delta-cells could regenerate, and both self-duplication and regeneration from
      endocrine precursor cells were involved in their regeneration.

PMID- 22586490
TI  - Role of the polarity protein Scribble for podocyte differentiation and
      maintenance.
AB  - The kidney filter represents a unique assembly of podocyte epithelial cells that
      tightly enwrap the glomerular capillaries with their complex foot process
      network. While deficiency of the polarity proteins Crumbs and aPKC result in
      impaired podocyte foot process architecture, the function of basolateral polarity
      proteins for podocyte differentiation and maintenance remained unclear. Here we
      report, that Scribble is expressed in developing podocytes, where it translocates
      from the lateral aspects of immature podocytes to the basal cell membrane and
      foot processes of mature podocytes. Immunogold electron microscopy reveals
      membrane associated localisation of Scribble predominantly at the basolateral
      site of foot processes. To further study the role of Scribble for podocyte
      differentiation Scribble(flox/flox) mice were generated by introducing loxP-sites
      into the Scribble introns 1 and 8 and these mice were crossed to NPHS2.Cre mice
      and Cre deleter mice. Podocyte-specific Scribble knockout mice develop normally
      and display no histological, ultrastructural or clinical abnormalities up to 12
      months of age. In addition, no increased susceptibility to glomerular stress
      could be detected in these mice. In contrast, constitutive Scribble knockout
      animals die during embryonic development indicating the fundamental importance of
      Scribble for embryogenesis. Like in podocyte-specific Scribble knockout mice, the
      development of podocyte foot processes and the slit diaphragm was unaffected in
      kidney cultures from constitutive Scribble knockout animals. In summary these
      results indicate that basolateral polarity signaling via Scribble is dispensable
      for podocyte function, highlighting the unique feature of podocyte development
      with its significant apical membrane expansions being dominated by apical
      polarity complexes rather than by basolateral polarity signaling.

PMID- 22586491
TI  - High adherence is necessary to realize health gains from water quality
      interventions.
AB  - BACKGROUND: Safe drinking water is critical for health. Household water treatment
      (HWT) has been recommended for improving access to potable water where existing
      sources are unsafe. Reports of low adherence to HWT may limit the usefulness of
      this approach, however. METHODS AND FINDINGS: We constructed a quantitative
      microbial risk model to predict gains in health attributable to water quality
      interventions based on a range of assumptions about pre-treatment water quality;
      treatment effectiveness in reducing bacteria, viruses, and protozoan parasites;
      adherence to treatment interventions; volume of water consumed per person per
      day; and other variables. According to mean estimates, greater than 500 DALYs may
      be averted per 100,000 person-years with increased access to safe water, assuming
      moderately poor pre-treatment water quality that is a source of risk and high
      treatment adherence (>90% of water consumed is treated). A decline in adherence
      from 100% to 90% reduces predicted health gains by up to 96%, with sharpest
      declines when pre-treatment water quality is of higher risk. CONCLUSIONS: Results
      suggest that high adherence is essential in order to realize potential health
      gains from HWT.

PMID- 22586493
TI  - Repression of cardiac hypertrophy by KLF15: underlying mechanisms and therapeutic
      implications.
AB  - The Kruppel-like factor (KLF) family of transcription factors regulates diverse
      cell biological processes including proliferation, differentiation, survival and
      growth. Previous studies have shown that KLF15 inhibits cardiac hypertrophy by
      repressing the activity of pivotal cardiac transcription factors such as GATA4,
      MEF2 and myocardin. We set out this study to characterize the interaction of
      KLF15 with putative other transcription factors. We first show that KLF15
      interacts with myocardin-related transcription factors (MRTFs) and strongly
      represses the transcriptional activity of MRTF-A and MRTF-B. Second, we
      identified a region within the C-terminal zinc fingers of KLF15 that contains the
      nuclear localization signal. Third, we investigated whether overexpression of
      KLF15 in the heart would have therapeutic potential. Using recombinant adeno
      associated viruses (rAAV) we have overexpressed KLF15 specifically in the mouse
      heart and provide the first evidence that elevation of cardiac KLF15 levels
      prevents the development of cardiac hypertrophy in a model of Angiotensin II
      induced hypertrophy.

PMID- 22586492
TI  - EGFR-mediated carcinoma cell metastasis mediated by integrin alphavbeta5 depends
      on activation of c-Src and cleavage of MUC1.
AB  - Receptor tyrosine kinases and integrins play an essential role in tumor cell
      invasion and metastasis. We previously showed that EGF and other growth factors
      induce human carcinoma cell invasion and metastasis mediated by integrin
      alphavbeta5 that is prevented by Src blockade. MUC1, a transmembrane
      glycoprotein, is expressed in most epithelial tumors as a heterodimer consisting
      of an extracellular and a transmembrane subunit. The MUC1 cytoplasmic domain of
      the transmembrane subunit (MUC1.CD) translocates to the nucleus where it promotes
      the transcription of a metastatic gene signature associated with epithelial to
      mesenchymal transition. Here, we demonstrate a requirement for MUC1 in carcinoma
      cell metastasis dependent on EGFR and Src without affecting primary tumor growth.
      EGF stimulates Src-dependent MUC1 cleavage and nuclear localization leading to
      the expression of genes linked to metastasis. Moreover, expression of MUC1.CD
      results in its nuclear localization and is sufficient for transcription of the
      metastatic gene signature and tumor cell metastasis. These results demonstrate
      that EGFR and Src activity contribute to carcinoma cell invasion and metastasis
      mediated by integrin alphavbeta5 in part by promoting proteolytic cleavage of
      MUC1 and highlight the ability of MUC1.CD to promote metastasis in a context
      dependent manner. Our findings may have implications for the use and future
      design of targeted therapies in cancers known to express EGFR, Src, or MUC1.

PMID- 22586494
TI  - Impact of the resident microbiota on the nutritional phenotype of Drosophila
      melanogaster.
AB  - BACKGROUND: Animals are chronically infected by benign and beneficial
      microorganisms that generally promote animal health through their effects on the
      nutrition, immune function and other physiological systems of the host. Insight
      into the host-microbial interactions can be obtained by comparing the traits of
      animals experimentally deprived of their microbiota and untreated animals.
      Drosophila melanogaster is an experimentally tractable system to study host
      microbial interactions. METHODOLOGY/PRINCIPAL FINDINGS: The nutritional
      significance of the microbiota was investigated in D. melanogaster bearing
      unmanipulated microbiota, demonstrated by 454 sequencing of 16S rRNA amplicons to
      be dominated by the alpha-proteobacterium Acetobacter, and experimentally
      deprived of the microbiota by egg dechorionation (conventional and axenic flies,
      respectively). In axenic flies, larval development rate was depressed with no
      effect on adult size relative to conventional flies, indicating that the
      microbiota promotes larval growth rates. Female fecundity did not differ
      significantly between conventional and axenic flies, but axenic flies had
      significantly reduced metabolic rate and altered carbohydrate allocation,
      including elevated glucose levels. CONCLUSIONS/SIGNIFICANCE: We have shown that
      elimination of the resident microbiota extends larval development and perturbs
      energy homeostasis and carbohydrate allocation patterns of of D. melanogaster.
      Our results indicate that the resident microbiota promotes host nutrition and
      interacts with the regulation of host metabolism.

PMID- 22586495
TI  - Importance of human leukocyte antigen (HLA) class I and II alleles on the risk of
      multiple sclerosis.
AB  - Multiple sclerosis (MS) is a complex disease of the central nervous system of
      unknown etiology. The human leukocyte antigen (HLA) locus on chromosome 6 confers
      a considerable part of the susceptibility to MS, and the most important factor is
      the class II allele HLA-DRB1*15:01. In addition, we and others have previously
      established a protective effect of HLA-A*02. Here, we genotyped 1,784 patients
      and 1,660 healthy controls from Scandinavia for the HLA-A, HLA-B, HLA-C and HLA
      DRB1 genes and investigated their effects on MS risk by logistic regression.
      Several allele groups were found to exert effects independently of DRB1*15 and
      A*02, in particular DRB1*01 (OR = 0.82, p = 0.034) and B*12 (including B*44/45,
      OR = 0.76, p = 0.0028), confirming previous reports. Furthermore, we observed
      interaction between allele groups: DRB1*15 and DRB1*01 (multiplicative: OR =
      0.54, p = 0.0041; additive: AP = 0.47, p = 4 * 10(-06)), DRB1*15 and C*12
      (multiplicative: OR = 0.37, p = 0.00035; additive: AP = 0.58, p = 2.6 * 10(-05)),
      indicating that the effect size of these allele groups varies when taking DRB1*15
      into account. Analysis of inferred haplotypes showed that almost all DRB1*15
      bearing haplotypes were risk haplotypes, and that all A*02 bearing haplotypes
      were protective as long as they did not carry DRB1*15. In contrast, we found one
      class I haplotype, carrying A*02-C*05-B*12, which abolished the risk of DRB1*15.
      In conclusion, these results confirms a complex role of HLA class I and II genes
      that goes beyond DRB1*15 and A*02, in particular by including all three classical
      HLA class I genes as well as functional interactions between DRB1*15 and several
      alleles of DRB1 and class I genes.

PMID- 22586497
TI  - Suppressive effects of Schizandra chinensis Baillon water extract on allergy
      related cytokine generation and degranulation in IgE-antigen complex-stimulated
      RBL-2H3 cells.
AB  - Schizandra chinensis Baillon is a traditional folk medicine plant that is used to
      treat and prevent several inflammatory diseases and cancer in Korea, but the
      underlying mechanisms involved in its anti-allergic activity are not fully
      understood. This study was designed to investigate mechanisms of anti-allergic
      activity of a Schizandra chinensis Baillon water extract (SCWE) in immunoglobulin
      E (IgE)-antigen complex-stimulated RBL2H3 cells and to assess whether gastric and
      intestinal digestion affects the anti-allergic properties of SCWE. Oxidative
      stress is an important consequence of the allergic inflammatory response. The
      antioxidant activities of SCWE increased in a concentration-dependent manner. RBL
      2H3 cells were sensitized with monoclonal anti-dinitrophenol (DNP) specific IgE,
      treated with SCWE, and challenged with the antigen DNP-human serum albumin. SCWE
      inhibited beta-hexosaminidase release and expression of interleukin (IL)-4, IL
      13, and tumor necrosis factor-alpha (TNF-alpha) mRNA and protein in IgE-antigen
      complex-stimulated RBL2H3 cells. We found that digested SCWE fully maintained its
      antioxidant activity and anti-allergic activity against the IgE-antigen complex
      induced activation of RBL-2H3 cells. SCWE may be useful for preventing allergic
      diseases, such as asthma. Thus, SCWE could be used as a natural functional
      ingredient for allergic diseases in the food and/or pharmaceutical industries.

PMID- 22586496
TI  - Extracellular matrix mineralization promotes E11/gp38 glycoprotein expression and
      drives osteocytic differentiation.
AB  - Osteocytes are terminally differentiated osteoblasts which reside in a
      mineralized extracellular matrix (ECM). The factors that regulate this
      differentiation process are unknown. We have investigated whether ECM
      mineralization could promote osteocyte formation. To do this we have utilised MLO
      A5 pre-osteocyte-like cells and western blotting and comparative RT-PCR to
      examine whether the expression of osteocyte-selective markers is elevated
      concurrently with the onset of ECM mineralization. Secondly, if mineralization of
      the ECM is indeed a driver of osteocyte formation, we reasoned that impairment of
      ECM mineralization would result in a reversible inhibition of osteocyte
      formation. Supplementation of MLO-A5 cell cultures with ascorbic acid and
      phosphate promoted progressive ECM mineralization as well as temporally
      associated increases in expression of the osteocyte-selective markers, E11/gp38
      glycoprotein and sclerostin. Consistent with a primary role for ECM
      mineralization in osteocyte formation, we also found that inhibition of ECM
      mineralization, by omitting phosphate or adding sodium pyrophosphate, a
      recognized inhibitor of hydroxyapatite formation, resulted in a 15-fold decrease
      in mineral deposition that was closely accompanied by lower expression of E11 and
      other osteocyte markers such as Dmp1, Cd44 and Sost whilst expression of
      osteoblast markers Ocn and Col1a increased. To rule out the possibility that such
      restriction of ECM mineralization may produce an irreversible modification in
      osteoblast behaviour to limit E11 expression and osteocytogenesis, we also
      measured the capacity of MLO-A5 cells to re-enter the osteocyte differentiation
      programme. We found that the mineralisation process was re-initiated and closely
      allied to increased expression of E11 protein after re-administration of
      phosphate or omission of sodium pyrophosphate, indicating an ECM mineralization
      induced restoration in osteocyte formation. These results emphasise the
      importance of cell-ECM interactions in regulating osteoblast behaviour and, more
      importantly, suggest that ECM mineralization exerts pivotal control during
      terminal osteoblast differentiation and acquisition of the osteocyte phenotype.

PMID- 22586498
TI  - Effects of green tea or Sasa quelpaertensis bamboo leaves on plasma and liver
      lipids, erythrocyte Na efflux, and platelet aggregation in ovariectomized rats.
AB  - This study was conducted to investigate the effects of Sasa quelpaertensis bamboo
      and green tea on plasma and liver lipids, platelet aggregation, and erythrocyte
      membrane Na channels in ovariectomized (OVX) rats. Thirty female rats were OVX,
      and ten female rats were sham-operated at the age of 6 weeks. The rats were
      divided into four groups at the age of 10 weeks and fed the experiment diets:
      sham-control, OVX-control, OVX-bamboo leaves (10%), or OVX-green tea leaves (10%)
      for four weeks. Final body weight increased significantly in the OVX groups
      compared with that in the sham-control, whereas body weight in the OVX-green tea
      group decreased significantly compared with that in the OVX-control (P < 0.01).
      High density lipoprotein (HDL)-cholesterol level decreased in all OVX groups
      compared with that in the sham-control rats (P < 0.05) but without a difference
      in plasma total cholesterol. Plasma triglycerides in the OVX-green tea group were
      significantly lower than those in the sham-control or OVX-control group (P <
      0.05). Liver triglycerides increased significantly in the OVX-control compared
      with those in the sham-control (P < 0.01) but decreased significantly in the OVX
      green tea group compared with those in the OVX-control or OVX-bamboo group (P <
      0.01). Platelet aggregation in both maximum and initial slope tended to be lower
      in all OVX rats compared with that in the sham-control rats but was not
      significantly different. Na-K ATPase tended to increase and Na-K cotransport
      tended to decrease following ovariectomy. Na-K ATPase decreased significantly in
      the OVX-green tea group compared with that in the OVX-control group (P < 0.01),
      and Na-K cotransport increased significantly in the OVX-bamboo and OVX-green tea
      groups compared with that in the OVX-control (P < 0.05). Femoral bone mineral
      density tended to be lower in OVX rats than that in the sham-control, whereas the
      green tea and bamboo leaves groups recovered bone density to some extent. The
      results show that ovariectomy caused an increase in body weight and liver
      triglycerides, and that green tea was effective for lowering body weight and
      triglycerides in OVX rats. Ovariectomy induced an increase in Na efflux via Na-K
      ATPase and a decrease in Na efflux via Na-K cotransport. Furthermore, consumption
      of green tea and bamboo leaves affected Na efflux channels, controlling
      electrolyte and body water balance.

PMID- 22586499
TI  - Lutein decreases oxidative stress and inflammation in liver and eyes of guinea
      pigs fed a hypercholesterolemic diet.
AB  - Guinea pigs were fed a hypercholesterolemic diet (0.25 g/100 g cholesterol) and
      randomly allocated either to a Control group (n = 9) or to a Lutein (0.1 g/100 g)
      group (n = 10) for 12 weeks to evaluate oxidative stress and inflammation in both
      liver and eyes. Malondialdehyde (MDA) concentrations and inflammatory cytokines
      were measured as well as hepatic nuclear factor-kappaB (NF-kappaB) binding.
      Lutein concentrations were greater in eyes (P < 0.01) and liver (P < 0.001) in
      the Lutein group. All guinea pigs had high concentrations of hepatic cholesterol
      as well as high plasma ALT and AST levels indicative of liver injury. However,
      the Lutein group had 43% lower hepatic free cholesterol than the Controls (P <
      0.05). Hepatic MDA and MDA in the eye were lower in the Lutein compared to the
      Control group (P < 0.05). Hepatic tumor necrosis factor-alpha was 32% lower in
      the Lutein group (P < 0.05). Lastly, the Lutein group presented lower NF-kappaB
      DNA binding activity than the Control group (P < 0.001). These results suggest
      that in the presence of high cholesterol, lutein exerts both antioxidant and anti
      inflammatory effects, which can be explained by attenuated NF-kappaB DNA binding
      activity. Furthermore, results also suggest that lutein accumulates in the eyes
      of guinea pigs to protect against oxidative stress.

PMID- 22586500
TI  - Higher levels of serum triglyceride and dietary carbohydrate intake are
      associated with smaller LDL particle size in healthy Korean women.
AB  - The aim of this study was to investigate the influencing factors that
      characterize low density lipoprotein (LDL) phenotype and the levels of LDL
      particle size in healthy Korean women. In 57 healthy Korean women (mean age, 57.4
      +/- 13.1 yrs), anthropometric and biochemical parameters such as lipid profiles
      and LDL particle size were measured. Dietary intake was estimated by a developed
      semi-quantitative food frequency questionnaire. The study subjects were divided
      into two groups: LDL phenotype A (mean size: 269.7A, n = 44) and LDL phenotype B
      (mean size: 248.2A, n = 13). Basic characteristics were not significantly
      different between the two groups. The phenotype B group had a higher body mass
      index, higher serum levels of triglyceride, total-cholesterol, LDL-cholesterol,
      apolipoprotein (apo)B, and apoCIII but lower levels of high density lipoprotein
      (HDL)-cholesterol and LDL particle size than those of the phenotype A group. LDL
      particle size was negatively correlated with serum levels of triglyceride (r = 
      0.732, P < 0.001), total-cholesterol, apoB, and apoCIII, as well as carbohydrate
      intake (%En) and positively correlated with serum levels of HDL-cholesterol and
      ApoA1 and fat intake (%En). A stepwise multiple linear regression analysis
      revealed that carbohydrate intake (%En) and serum triglyceride levels were the
      primary factors influencing LDL particle size (P < 0.001, R(2) = 0.577). This
      result confirmed that LDL particle size was closely correlated with circulating
      triglycerides and demonstrated that particle size is significantly associated
      with dietary carbohydrate in Korean women.

PMID- 22586502
TI  - Maternal anthropometric measurements and other factors: relation with birth
      weight of neonates.
AB  - The objective of this study was to examine the influence of anthropometric
      measurements of pregnant women, gestational weight gain, fundal height, and
      maternal factors, namely age, education, family income, parity along with
      maternal hemoglobin, on birth weight of neonates. A cross sectional study was
      performed in Khoy City in north west of Iran. Four hundred and fifty healthy
      pregnant women in the age between 16-40 years were selected for this study from
      seven health urban centers and one referral hospital. Findings showed that the
      mean age, height, fundal height, maternal weight, and gestational weight gain
      during pregnancy were 26.1 years, 159.1 cm, 32.9 cm, 72.0 kg, 11.8 kg
      respectively. The mean birth weight of neonates was 3.2 kg and 11% of neonates
      showed low birth weight. Age, family income, maternal height, weight, gestational
      weight gain and fundal height were significantly associated with birth weight of
      neonates. Using binary logistic regression analysis, fundal height, maternal
      hemoglobin, family income and gestational weight gain of pregnant women could be
      considered as predictive factors of birth weight of neonates.

PMID- 22586501
TI  - Effects of rehydration fluid temperature and composition on body weight retention
      upon voluntary drinking following exercise-induced dehydration.
AB  - The purpose of this study was to determine the effects of beverage temperature
      and composition on weight retention and fluid balance upon voluntary drinking
      following exercise induced-dehydration. Eight men who were not acclimated to heat
      participated in four randomly ordered testing sessions. In each session, the
      subjects ran on a treadmill in a chamber maintained at 37C without being supplied
      fluids until 2% body weight reduction was reached. After termination of exercise,
      they recovered for 90 min under ambient air conditions and received one of the
      following four test beverages: 10C water (10W), 10C sports drink (10S), 26C water
      (26W), and 26C sports drink (26S). They consumed the beverages ad libitum. The
      volume of beverage consumed and body weight were measured at 30, 60, and 90 min
      post-recovery. Blood samples were taken before and immediately after exercise as
      well as at the end of recovery in order to measure plasma parameters and
      electrolyte concentrations. We found that mean body weight decreased by 1.8-2.0%
      following exercise. No differences in mean arterial pressure, plasma volume,
      plasma osmolality, and blood electrolytes were observed among the conditions.
      Total beverage volumes consumed were 1,164 +/- 388, 1,505 +/- 614, 948 +/- 297,
      and 1,239 +/- 401 ml for 10W, 10S, 26W, and 26S respectively (P > 0.05). Weight
      retention at the end of recovery from dehydration was highest in 10S (1.3 +/- 0.7
      kg) compared to 10W (0.4 +/- 0.5 kg), 26W (0.4 +/- 0.4 kg), and (0.6 +/- 0.4 kg)
      (P < 0.005). Based on these results, carbohydrate/electrolyte-containing
      beverages at cool temperature were the most favorable for consumption and weight
      retention compared to plain water and moderate temperature beverages.

PMID- 22586503
TI  - The effect of a healthy school tuck shop program on the access of students to
      healthy foods.
AB  - The objective of this study was to evaluate the effect of a healthy school tuck
      shop program, developed as a way of creating a healthy and nutritional school
      environment, on students' access to healthy foods. Five middle schools and four
      high schools (775 students) participated in the healthy school tuck shop program,
      and nine schools (1,282 students) were selected as the control group. The
      intervention program included restriction of unhealthy foods sold in tuck shops,
      provision of various fruits, and indirect nutritional education with promotion of
      healthy food products. The program evaluation involved the examination of
      students' purchase and intake patterns of healthy foods, satisfaction with the
      available foodstuffs, and utilization of and satisfaction with nutritional
      educational resources. Our results indicated that among of the students who
      utilized the tuck shop, about 40% purchased fruit products, showing that
      availability of healthy foods in the tuck shop increased the accessibility of
      healthy foods for students. Overall food purchase and intake patterns did not
      significantly change during the intervention period. However, students from the
      intervention schools reported higher satisfaction with the healthy food products
      sold in the tuck shop than did those from the control schools (all P < 0.001),
      and they were highly satisfied with the educational resources provided to them.
      In conclusion, the healthy school tuck shop program had a positive effect on the
      accessibility of healthy food. The findings suggest that a healthy school tuck
      shop may be an effective environmental strategy for promoting students' access to
      healthy foods.

PMID- 22586504
TI  - Drinking behaviors by stress level in Korean university students.
AB  - The purposes of this study are to estimate the stress level of university
      students, and to verify the relationships between stress level and drinking
      behavior. A questionnaire survey was administered to 430 university students in
      the Gangwon area in Korea from November 5 to November 28, 2008, and data from 391
      students were used for the final statistical analysis. The most stressful factor
      was "Worry about academic achievements" (2.86 by Likert-type 4 point scale). The
      subjects were divided into two groups, a low stress group (<= 65.0) and a high
      stress group (>= 66.0), by the mean value (65.1) and median value (66.0) of the
      stress levels. The drinking frequency was not different between the two stress
      groups, but the amount of alcohol consumption was significantly different (P <
      0.05). The portion of students reporting drinking "7 glasses or over" was higher
      in the lower stress group than in the higher stress group. In addition, factor 6,
      "Lack of learning ability", was negatively correlated with drinking frequency and
      the amount of alcohol consumption (P < 0.05), and factor 3, "Worry about academic
      achievements", was negatively correlated with the amount of drinking (P < 0.05).
      The major motive for drinking was "When overjoyed or there is something to
      celebrate" (2.62), and the main expected effect of drinking was "Drinking enables
      me to get together with people and shape my sociability" (2.73). The higher
      stress group showed significantly higher scores on several items in the
      categories of motives (P < 0.01), negative experience (P < 0.05), and expected
      effects (P < 0.05) of drinking than the lower stress group. Our results imply
      that university students at the lower stress level may drink more from social
      motives in positive drinking environments, while those at the higher stress level
      may have more problematic-drinking despite their smaller amount of alcohol
      consumption.

PMID- 22586505
TI  - Long-term vegetarians have low oxidative stress, body fat, and cholesterol
      levels.
AB  - Excessive oxidative stress and abnormal blood lipids may cause chronic diseases.
      This risk can be reduced by consuming an antioxidant- and fiber-rich vegetarian
      diet. We compared biomarkers of oxidative stress, antioxidant capacity, and lipid
      profiles of sex- and age-matched long-term vegetarians and omnivores in Korea.
      Forty-five vegetarians (23 men and 22 women; mean age, 49.5 +/- 5.3 years), who
      had maintained a vegetarian diet for a minimum of 15 years, and 30 omnivores (15
      men and 15 women; mean age, 48.9 +/- 3.6 years) participated in this study. Their
      1-day, 24-h recall, and 2-day dietary records were analyzed. Oxidative stress was
      measured by the levels of diacron reactive oxygen metabolites (d-ROM).
      Antioxidant status was determined by the biological antioxidant potential (BAP)
      and levels of endogenous antioxidant enzymes such as superoxide dismutase,
      catalase, and glutathione peroxidase. We observed that vegetarians had a
      significantly lower body fat percentage (21.6 +/- 6.4%) than that of omnivores
      (25.4 +/- 4.6%; P < 0.004). d-ROM levels were significantly lower in vegetarians
      than those in omnivores (331.82 +/- 77.96 and 375.80 +/- 67.26 Carratelli units;
      P < 0.011). Additionally, total cholesterol levels in the vegetarians and
      omnivores were 173.73 +/- 31.42 mg/dL and 193.17 +/- 37.89 mg/dL, respectively (P
      < 0.018). Low-density lipoprotein cholesterol was 101.36 +/- 23.57 mg/dL and
      120.60 +/- 34.62 mg/dL (P < 0.005) in the vegetarians and omnivores,
      respectively, indicating that vegetarians had significantly lower lipid levels.
      Thus, oxidative stress, body fat, and cholesterol levels were lower in long-term
      vegetarians than those in omnivores.

PMID- 22586506
TI  - Vitamin D deficiency is an independent risk factor for cardiovascular disease in
      Koreans aged >= 50 years: results from the Korean National Health and Nutrition
      Examination Survey.
AB  - Vitamin D deficiency is a risk factor for metabolic syndromes. We examined
      whether vitamin D deficiency altered the prevalence of cardiovascular disease
      (CVD) in older Koreans. Cross-sectional analysis of data from the Korean National
      Health and Nutrition Examination Survey IV 2008-2009 was used to examine the
      association between serum 25-hydroxyvitamin D (25(OH)D) levels and the prevalence
      of CVD in a representative population-based sample of 5,559 men and women aged >=
      50 years. CVD was defined as angina pectoris, myocardial infarction, or stroke.
      The prevalence of CVD (7.0%) in the older Korean population was lower than that
      in the older US population, although average serum 25(OH)D levels were much lower
      in the Korean population. Additionally, serum 25(OH)D levels did not differ
      significantly between the CVD and non-CVD groups. However, subjects in the lowest
      category (< 25 nmol/l) of serum 25(OH)D level had the greatest prevalence of CVD,
      about two-fold higher than subjects in the highest category (> 75 nmol/l), after
      adjusting for age, gender, body mass index, education level, residence location,
      and region. The prevalence of other risk factors for CVD, including higher waist
      circumference, fasting glucose, low-density lipoprotein (LDL) cholesterol, and
      triglyceride levels and lower high-density lipoprotein (HDL) cholesterol levels,
      was also higher among subjects in the lowest category than among those in the
      highest category. In conclusion, low serum 25(OH)D may be an independent risk
      factor for CVD in older Koreans.

PMID- 22586507
TI  - The effects of food safety education on adolescents' hand hygiene behavior: an
      analysis of stages of change.
AB  - The hand hygiene behavior of 400 middle school students (grades 1-3) in Seoul and
      Gyeonggi-Do was studied to determine how stages of change were affected by food
      safety education, focusing on hand hygiene and general food safety. Subjects were
      51.3% male and 44.3% of study subjects were first graders of middle school.
      Approximately 40% of subjects were at the stage of action, 42.7% were at the
      stage of contemplation, and 16.4% were at pre-contemplation. The most important
      factor that influenced proper hand washing was self efficacy (P < 0.001). Proper
      hand washing was also correlated significantly with positive belief (P < 0.01)
      and stages of change (P < 0.01). After food safety education by high-school
      mentors, middle-school students who were in the stages of pre-contemplation
      (11.1%) and contemplation (88.9%) showed significant progression toward the
      action stage (P < 0.001). Proper hand washing (P < 0.01) and food safety
      knowledge (P < 0.05) were also significantly increased after educational
      intervention.

PMID- 22586508
TI  - Body image distortion in fifth and sixth grade students may lead to stress,
      depression, and undesirable dieting behavior.
AB  - The widespread pursuit of a thin physique may have a detrimental impact on the
      wellbeing of preadolescents. The influence of body image distortions on the
      lifestyles, dieting behaviors, and psychological factors was investigated in 631
      fifth and sixth grade children in Kyeonggi-do, Korea. Children were classified
      into three weight groups (underweight, normal, and overweight) and three
      perception groups (underestimation, normal, and overestimation). Necessary
      information was obtained by questionnaire, and each subject's weight status was
      determined by the Rohrer index calculated from the annual measurement records,
      which were obtained from the school. According to their current weights, 57.4% of
      children were normal and 32.2% were overweight or obese, 16.6% of the children
      overestimated their body weight, and 55.2% had an undistorted body image.
      Overweight children had desirable lifestyles and dietary habits and presented
      reasonable weight control behaviors. Compared to those without distortion, the
      overestimated group had greater interest in weight control (P = 0.003) and
      dissatisfaction with their body weights (P = 0.011), presented unhealthy reasons
      to lose weight (P = 0.026), and had higher scores for "feeling sad when comparing
      own body with others" (P = 0.000) and for "easily getting annoyed and tired" (P =
      0.037), even though they had similar obesity indices. More subjects from the
      overestimation group (P = 0.006) chose drama/movies as their favorite TV
      programs, suggesting a possible role for the media in body image distortion.
      These findings suggest that body image distortion can lead preadolescents to
      develop stress about obesity and unhealthy dieting practices, despite similar
      obesity indices to those without distorted body images. These results emphasize
      the importance of having an undistorted body image.

PMID- 22586509
TI  - Moving forward with new data and approaches: a fresh look at anthracyclines in
      non-Hodgkin's lymphoma.
AB  - Anthracyclines have a central role in the management of non-Hodgkin's lymphoma
      (NHL). The cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)
      treatment regimen has been the standard of care for more than 20 years. Further
      improvements have been made to the efficacy of this chemotherapy by reducing the
      dosing interval and adding rituximab to the regimen. A major limitation to the
      use of anthracyclines is the development of cardiotoxicity as a late adverse
      event. Strategies to reduce cardiac events include changes to the dosing schedule
      for doxorubicin, use of the chelating agent dexrazoxane and the use of liposome
      encapsulated doxorubicin. This latter strategy has demonstrated good efficacy and
      reduced cardiotoxicity in patients with NHL, including those at risk of
      developing cardiac effects.

PMID- 22586510
TI  - The use of molecular profiling for diagnosis and research in non-Hodgkin's
      lymphoma.
AB  - Molecular profiling facilitates the understanding of the genetic processes
      underlying the development of cancer, and makes it possible to use specific
      signatures to prognosticate clinical outcome and to predict response to specific
      treatments. There has been a great increase in the availability of tools for
      exploring genetic abnormalities in cancer cells, which have allowed a more
      comprehensive characterization of the mutations, translocations, and copy-number
      variations that may affect the development of cancer or therapy response. An
      improved understanding of the molecular basis of cancer is helping also in the
      identification of new molecular targets for therapy.

PMID- 22586511
TI  - Current approaches to the treatment of non-Hodgkin's lymphoma.
AB  - Chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone
      (CHOP) has long been a standard treatment for lymphoma. Improvements to the
      efficacy of this regimen can be made by increasing the doses of doxorubicin and
      cyclophosphamide, as in the chemotherapeutic regimen of doxorubicin,
      cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP), and by reducing
      the standard dosing interval, as seen with the CHOP-14 regimen. Adding the
      immunotherapeutic agent rituximab (R) to either CHOP or ACVBP has been shown to
      improve outcomes significantly, such that six cycles of R-CHOP plus two cycles of
      ritux-imab are as effective as eight cycles of R-CHOP, and R-CHOP-21 appears to
      be at least as effective as the more dose-intense R-CHOP-14. In patients who have
      several adverse prognostic factors, R-ACVBP plus autologous stem-cell
      transplantation has been shown to produce good treatment outcomes. The use of
      positron emission tomography scanning before and early in treatment should allow
      prediction of long-term outcomes, and therefore the adaptation of treatment to
      individual prognosis and treatment needs. In patients with follicular lymphoma,
      rituximab has been shown to improve the efficacy of conventional chemotherapies.
      In addition, rituximab alone or yttrium-90-ibritumomab tiuxetan are effective
      maintenance therapies in this condition.

PMID- 22586512
TI  - Anthracyclines: a cornerstone in the management of non-Hodgkin's lymphoma.
AB  - Since anthracyclines were introduced in the treatment of non-Hodgkin's lymphoma
      in the late 1960s, they have been acknowledged as a cornerstone in the management
      of the disease and, in particular, of aggressive lymphomas. The high efficacy of
      anthracycline-containing regimens must, however, be balanced against the drug
      related toxicity, which mainly affects the cardiovascular system and represents a
      major concern for clinicians, especially in the treatment of elderly patients.
      Patients' outcomes could be further improved, particularly for those at high risk
      of cardiotoxicity, by substituting liposomal doxorubicin for conventional
      doxorubicin. This approach has already been tested and shown to be effective in
      several cancers, especially in different subsets of patients with diffuse large B
      cell lymphoma. The use of liposomal doxorubicin in combination regimens for other
      conditions, such as follicular lymphoma and splenic marginal zone lymphoma, is
      also under investigation, and early results are promising.

PMID- 22586513
TI  - Ongoing trials in low-grade lymphoma.
AB  - There are many therapies available for the management of low-grade lymphoma. With
      follicular lymphoma, for example, combination of chemotherapy and rituximab
      (immuno-chemotherapy) and consecutive maintenance therapy for 2 years is the
      current standard of care. To date, the most widely used regimen seems to be
      rituximab combined with cyclophosphamide, doxorubicin, vincristine, and
      prednisone (R-CHOP). Substitution of liposomal doxorubicin in place of
      conventional doxorubicin may improve outcomes in this indication, although
      evidence for its use in low-grade lymphoma is not as relevant as in aggressive
      lymphoma. Bendamustine, in combination with rituximab, has shown very good
      efficacy and tolerability in several lymphoma types, particularly follicular
      lymphoma and other low-grade lymphomas. Other combinations, such as those
      including bortezomib and lenalidomide, are under investigation in low-grade
      lymphoma, and the duration of rituximab maintenance therapy following
      bendamustine-rituximab-containing induction is being researched by the German
      Study Group for Indolent Lymphoma (StiL).

PMID- 22586514
TI  - SIOG (International Society of Geriatric Oncology) recommendations for
      anthracycline use in the elderly.
AB  - A taskforce of the International Society of Geriatric Oncology (SIOG) has
      recently submitted recommendations on the use of anthracyclines in elderly
      patients. Despite the aging of the population and the high proportion of elderly
      individuals in the population of patients with non-Hodgkin's lymphoma, the
      development of specialist expertise in the treatment of elderly patients with
      cancer is relatively recent. Treatment of the elderly is complex because they are
      a highly heterogeneous population, with large variations in health status,
      comorbidities and life expectancy. In addition, these patients are generally more
      susceptible than young patients to the cardiotoxic effects of anthracyclines.
      Strategies for assessing elderly patients with cancer, reducing the risk of
      congestive heart failure, and assessing the cardiotoxic effects of treatments are
      discussed. In addition, a summary of the SIOG recommendations is presented.

PMID- 22586515
TI  - Case studies of elderly patients with non-Hodgkin's lymphoma.

PMID- 22586516
TI  - Formation of nano-bio-complex as nanomaterials dispersed in a biological solution
      for understanding nanobiological interactions.
AB  - Information on how cells interface with nanomaterials in biological environments
      has important implications for the practice of nanomedicine and safety
      consideration of nanomaterials. However, our current understanding of
      nanobiological interactions is still very limited. Here, we report the direct
      observation of nanomaterial bio-complex formation (other than protein corona)
      from nanomaterials dispersed in biologically relevant solutions. We observed
      highly selective binding of the components of cell culture medium and phosphate
      buffered saline to ZnO and CuO nanoparticles, independent of protein molecules.
      Our discoveries may provide new insights into the understanding of how cells
      interact with nanomaterials.

PMID- 22586519
TI  - A tribute to a deceased genius.

PMID- 22586518
TI  - Focus issue: neck dissection for oropharyngeal squamous cell carcinoma.
AB  - The staging and prognosis of oropharyngeal squamous cell carcinoma is intimately
      tied to the status of the cervical lymph nodes. Due to the high risk for occult
      nodal disease, most clinicians recommend treating the neck for these primary
      tumors. While there are many modalities available, surgical resection of nodal
      disease offers both a therapeutic and a diagnostic intervention. We review the
      relevant anatomy, nodal drainage patterns, clinical workup, surgical management
      and common complications associated with neck dissection for oropharyngeal
      squamous cell carcinoma.

PMID- 22586517
TI  - Reduction of N2 by supported tungsten clusters gives a model of the process by
      nitrogenase.
AB  - Metalloenzymes catalyze difficult chemical reactions under mild conditions.
      Mimicking their functions is a challenging task and it has been investigated
      using homogeneous systems containing metal complexes. The nitrogenase that
      converts N(2) to NH(3) under mild conditions is one of such enzymes. Efforts to
      realize the biological function have continued for more than four decades, which
      has resulted in several reports of reduction of N(2), ligated to metal complexes
      in solutions, to NH(3) by protonation under mild conditions. Here, we show that
      seemingly distinct supported small tungsten clusters in a dry environment reduce
      N(2) under mild conditions like the nitrogenase. N(2) is reduced to NH(3) via
      N(2)H(4) by addition of neutral H atoms, which agrees with the mechanism recently
      proposed for the N(2) reduction on the active site of nitrogenase. The process on
      the supported clusters gives a model of the biological N(2) reduction.

PMID- 22586520
TI  - Antiplaque and antigingivitis effects of a mouthrinse containing cetylpyridinium
      chloride, triclosan and dipotassium glycyrrhizinate.
AB  - PURPOSE: The goal of this study was to evaluate the clinical anitplaque and
      antigingivitis effects of a mouthrinse containing cetylpyridinium chloride (CPC),
      triclosan and dipotassium glycyrrhizinate (DPZ) in patients with gingivitis and
      mild periodontitis. METHODS: Thirty-two subjects were randomized into 2 groups.
      The test group used a mouthrinse containing 0.05% CPC, 0.02% triclosan and 0.02%
      DPZ, while the control group used a placebo mouthrinse. At baseline, 2 weeks and
      4 weeks, the papillary bleeding index (PBI), Turesky-Quigley-Hein plaque index
      (PI) and Loe-Silness gingival index (GI) were assessed. During the experimental
      period, the patients used the mouthrinse for 30 seconds, 4 to 5 times/day (10
      mL/time) within 30 minutes after toothbrushing. RESULTS: No adverse effects
      appeared in either the experimental or the control group. Regarding PBI, PI and
      GI values, statistical significance was detected between values at baseline and 2
      weeks for both groups (P<0.05). In the experimental group, statistically
      significantly lower values were detected at 4 weeks compared to at 2 weeks.
      However, in the control group, no statistically significant difference was
      detected between the values at 2 weeks and 4 weeks. Additionally, the mean value
      after 4 weeks for the control group was slightly higher than the mean value after
      2 weeks for the control group. CONCLUSIONS: This study for 4 weeks demonstrated
      that mouthrinses containing CPC, triclosan and DPZ may contribute to the
      reduction of supragingival plaque and gingivitis.

PMID- 22586521
TI  - Reliability of two different presurgical preparation methods for implant
      dentistry based on panoramic radiography and cone-beam computed tomography in
      cadavers.
AB  - PURPOSE: Special care is necessary to avoid invading important anatomic
      structures during surgery when presurgical planning is made based on radiographs.
      However, none of these types of radiography represents a perfect modality. The
      purpose of this study was to determine the reliability of presurgical planning
      based on the use of two types of radiographic image (digital panoramic
      radiography [DPR] and cone-beam computed tomography [CBCT]) by beginner dentists
      to place implants, and to quantify differences in measurements between
      radiographic images and real specimens. METHODS: Ten fresh cadavers without
      posterior teeth were used, and twelve practitioners who had no experience of
      implant surgery performed implant surgery after 10 hours of basic instruction
      using conventional surgical guide based on CBCT or DPR. Two types of measurement
      error were evaluated: 1) the presurgical measurement error, defined as that
      between the presurgical and postsurgical measurements in each modality of
      radiographic analysis, and 2) the measurement error between postsurgical
      radiography and the real specimen. RESULTS: The mean presurgical measurement
      error was significantly smaller for CBCT than for DPR in the maxillary region,
      whereas it did not differ significantly between the two imaging modalities in the
      mandibular region. The mean measurement error between radiography and real
      specimens was significantly smaller for CBCT than for DPR in the maxillary
      region, but did not differ significantly in the mandibular region. CONCLUSIONS:
      Presurgical planning can be performed safely using DPR in the mandible; however,
      presurgical planning using CBCT is recommended in the maxilla when a structure in
      a buccolingual location needs to be evaluated because this imaging modality
      supplies buccolingual information that cannot be obtained from DPR.

PMID- 22586522
TI  - Comparison of pain intensity of anterior middle superior alveolar injection with
      infiltration anesthetic technique in maxillary periodontal surgery.
AB  - PURPOSE: The aim of the present clinical trial was to compare pain during
      injection of anterior middle superior alveolar (AMSA) technique with that of
      infiltration injection technique in the maxilla in periodontal flap surgeries of
      patients referring to the Department of Periodontics, Faculty of Dentistry,
      Tabriz University of Medical Sciences. METHODS: Twenty subjects with an age range
      of 20 to 40 years were selected for the present study. One side of the maxilla
      was randomly selected as the test side and the other as the control side using a
      flip of a coin. AMSA technique was used on the test side and infiltration
      technique was used on the control side for anesthesia. On both sides 2% lidocaine
      containing 1:80,000 epinephrine was used for anesthesia. The operator obtained
      the visual analogue scale for each patient immediately after the injection and
      immediately after surgery. Data was analyzed using descriptive statistical
      methods (frequency percentages, means and standard deviations) and Wilcoxon's
      test using SPSS ver. 13 (SPSS Inc.). Statistical significance was defined at
      P<0.05. RESULTS: There were no statistically significant differences in pain
      during injection between the two techniques (P=0.856). There were statistically
      significant differences in postoperative pain between the two injection
      techniques (P=0.024). CONCLUSIONS: Postoperative pain in AMSA injection technique
      was less than that in the infiltration technique. Therefore, the AMSA technique
      is preferable in the periodontal surgeries for the anesthesia of palatal tissues
      given the fact that it has other advantages, too.

PMID- 22586525
TI  - Meet the Executive Editor-in-Chief: Professor Joseph Leung.

PMID- 22586523
TI  - Periodontal tissue reaction to customized nano-hydroxyapatite block scaffold in
      one-wall intrabony defect: a histologic study in dogs.
AB  - PURPOSE: This study evaluated histologically the tissue responses to and the
      effects of a customized nano-hydroxyapatite (n-HA) block bone graft on
      periodontal regeneration in a one-wall periodontal-defect model. METHODS: A
      customized block bone for filling in the standardized periodontal defect was
      fabricated from prefabricated n-HA powders and a polymeric sponge. Bilateral
      4*4*5 mm (buccolingual width*mesiodistal width*depth), one-wall, critical-size
      intrabony periodontal defects were surgically created at the mandibular second
      and fourth premolars of five Beagle dogs. In each dog, one defect was filled with
      block-type HA and the other served as a sham-surgery control. The animals were
      sacrificed following an 8-week healing interval for clinical and histological
      evaluations. RESULTS: Although the sites that received an n-HA block showed
      minimal bone formation, the n-HA block was maintained within the defect with its
      original hexahedral shape. In addition, only a limited inflammatory reaction was
      observed at sites that received an n-HA block, which might have been due to the
      high stability of the customized block bone. CONCLUSIONS: In the limitation of
      this study, customized n-HA block could provide a space for periodontal tissue
      engineering, with minimal inflammation.

PMID- 22586526
TI  - Introduction to the fourth issue.

PMID- 22586524
TI  - Surface characteristics of a novel hydroxyapatite-coated dental implant.
AB  - PURPOSE: This study evaluated the surface characteristics and bond strength
      produced using a novel technique for coating hydroxyapatite (HA) onto titanium
      implants. METHODS: HA was coated on the titanium implant surface using a super
      high-speed (SHS) blasting method with highly purified HA. The coating was
      performed at a low temperature, unlike conventional HA coating methods. Coating
      thickness was measured. The novel HA-coated disc was fabricated. X-ray
      diffraction analysis was performed directly on the disc to evaluate
      crystallinity. Four novel HA-coated discs and four resorbable blast medium (RBM)
      discs were prepared. Their surface roughnesses and areas were measured. Five
      puretitanium, RBM-treated, and novel HA-coated discs were prepared. Contact angle
      was measured. Two-way analysis of variance and the post-hoc Scheffe's test were
      used to analyze differences between the groups, with those with a probability of
      P<0.05 considered to be statistically significant. To evaluate exfoliation of the
      coating layer, 7 sites on the mandibles from 7 mongrel dogs were used. Other
      sites were used for another research project. In total, seven novel HA-coated
      implants were placed 2 months after extraction of premolars according to the
      manufacturer's instructions. The dogs were sacrificed 8 weeks after implant
      surgery. Implants were removed using a ratchet driver. The surface of the
      retrieved implants was evaluated microscopically. RESULTS: A uniform HA coating
      layer was formed on the titanium implants with no deformation of the RBM titanium
      surface microtexture when an SHS blasting method was used. CONCLUSIONS: These HA
      coated implants exhibited increased roughness, crystallinity, and wettability
      when compared with RBM implants.

PMID- 22586527
TI  - Clinical and histopathological characteristics of patients with duodenal
      papillary tumors treated at Kitasato University East Hospital.

PMID- 22586528
TI  - EUS-guided biliary rendezvous using a short hydrophilic guidewire.
AB  - BACKGROUND AND STUDY AIMS: EUS-guided rendezvous technique for biliary access
      requires expert manipulation of the guidewire across the downstream stricture or
      papilla. Published literature reports usage of the long-wire system to prevent
      loss of wire during scope exchange. We studied the efficacy of using a short
      hydrophilic guidewire in EUS-guided rendezvous.  PATIENTS AND METHODS: This is a
      retrospective study conducted in a tertiary care referral centre. 15 patients
      underwent EUS-guided biliary rendezvous with short wire. EUS-guided
      transduodenal/transgastric puncture of the biliary system was performed, followed
      by anterograde placement of a hydrophilic short-wire (260 cm) across the
      downstream stricture and/or papilla. Retrograde access was then achieved by
      retrieving the trans-papillary wire, followed by standard ERCP intervention. Main
      outcome measurements were rates of procedural success and complications. 
      RESULTS: EUS-guided biliary rendezvous was successful in 14 patients (93.3%).
      Failure was seen in one patient due to a tight malignant biliary stricture. One
      patient had peri-choledochal bile tracking which did not require any specific
      treatment.  CONCLUSIONS: Short-wire system in EUS-guided biliary rendezvous is
      highly effective and safe. It is a useful salvage procedure for biliary
      cannulation in patients with accessible papilla.

PMID- 22586529
TI  - A pilot study of contrast harmonic endosonography using DEFINITYTM in the
      evaluation of suspected pancreatic and peri-ampullary malignancies.
AB  - AIM: Contrast harmonic endosonography (CHEUS) is not widely available. This study
      assessed the utility of CHEUS using DEFINITYTM, a second generation ultrasonic
      contrast agent, in the evaluation of suspected pancreatic and peri-ampullary
      malignancies.  METHODS: Prospectively enrolled patients with suspected pancreatic
      and peri-ampullary malignancies underwent EUS followed by CHEUS. The incremental
      yield of CHEUS over EUS was analyzed. The gold standard for diagnosis of
      malignancy was positive cytology or histology; a negative diagnosis for
      malignancy was based on negative cytology or histology and benign clinical
      course.  RESULTS: Twenty-nine patients were enrolled and underwent CHEUS. The
      final diagnoses were: pancreatic adenocarcinoma (16/29); metastases to pancreas
      (4/29); pancreatitis with inflammatory mass (4/29); normal pancreas with focal
      fat sparing (1/29); ampulla adenocarcinoma (2/29); serous cystic neoplasm (1/29);
      peri-pancreatic lymph node due to lymphoma (1/29). One bengin case of chronic
      pancreatitis had calcification casting artifacts that prevented accurate EUS
      examination and was excluded, leaving 28 cases for comparative analysis between
      EUS and CHEUS. CHEUS enhanced tumor margins. CHEUS detected vascular invasion
      missed by EUS in 2/16 patients with pancreatic adenocarcinoma. Masses appeared
      hypoechoic with EUS. With CHEUS malignant masses had an inhomogeneous hypoechoic
      pattern associated with abnormal vessels while lesions due to focal pancreatitis
      or fat sparing were characterized by diffuse enhancement (p<0.001).  CONCLUSION:
      CHEUS improved the visualization of tumor margins and vascular invasion, and
      differentiated benign from malignant masses.

PMID- 22586530
TI  - Exploring the optimal fluorescein dose in probe-based confocal laser
      endomicroscopy for colonic imaging.
AB  - BACKGROUND: Probe-based confocal laser endomicroscopy (pCLE) is an emerging
      method for in-vivo imaging of the gastrointestinal tract and requires a contrast
      agent. Fluorescein is the most commonly used agent. The optimal dose of
      fluorescein for pCLE in colon is unknown.  OBJECTIVE: Exploration of optimal dose
      of fluorescein for pCLE in colon.  DESIGN: Comparative, prospective pilot trail. 
      SETTING: Tertiary-care center.  PATIENTS: 18 participants underwent colonoscopy
      without complications.  INTERVENTIONS: pCLE videos were recorded in normal cecum,
      using 10% fluorescein intravenously.  MAIN OUTCOME MEASUREMENTS: For subjective
      analysis, pCLE videos were scored for quality, by 2 observers, independently and
      blinded to fluorescein dose. For objective analysis, signal-to-noise ratios (SNR)
      were calculated for each video by an expert.  RESULTS: 6 fluorescein doses were
      used, including 0.5 mL, 1 mL, 2.5 mL, 5 mL, 7.5 mL and 10 mL and each dose was
      used in three patients. For each dose, median image quality score was 2.5, 2.0,
      3.25, 4.0, 4.0 and 3.5 by first observer and 2.0, 3.0, 4.0, 5.0, 4.0 and 4.0 by
      second observer, respectively. The subjective quality scores increased from 0.5
      mL to 5.0 mL, with no evidence of further improved quality at 7.5 mL and 10 mL
      doses. SNR were not significantly different between doses but trended higher for
      higher doses.  LIMITATIONS: Small sample size. The results can not be applied to
      other parts of gastrointestinal tract i.e. duodenum, esophagus with different
      blood supply.  CONCLUSION: This preliminary study suggests that the optimal dose
      of fluorescein for high quality pCLE imaging in colon is approximately 5.0 mL.

PMID- 22586531
TI  - The water method is effective in difficult colonoscopy - it enhances cecal
      intubation in unsedated patients with a history of abdominal surgery.
AB  - BACKGROUND: Colonoscopy in unsedated patients in the US is considered to be
      difficult. Success rate of cecal intubation is limited by discomfort. Colonoscopy
      in patients with a history of abdominal surgery is also considered to be
      difficult due to adhesion-related bowel angulations. The water method has been
      shown to significantly reduce pain during colonoscopy.  OBJECTIVE: To test the
      hypothesis that the water method enhances the completion of colonoscopy in
      unsedated patients with a history of abdominal surgery.  DESIGN: The data bases
      of two parallel RCT were combined and analyzed.  SETTING: Two Veterans Affairs
      endoscopy units.  PATIENT AND METHODS: The water and air methods were compared in
      these two parallel RCT examining unsedated patients. Those with a history of
      abdominal surgery were selected for evaluation.  MAIN OUTCOME MEASUREMENTS:
      Completion of unsedated colonoscopy.  RESULTS: Among patients with a history of
      abdominal surgery, the proportion completing unsedated colonoscopy in the water
      group (19 of 22) was significantly higher than that (11 of 22) in the air group
      (p=0.0217, Fisher's exact test).  LIMITATIONS: Small number of predominantly male
      veterans, unblinded colonoscopists, not all types of abdominal surgery (e.g.
      hysterectomy, gastrectomy) predisposing to difficult colonoscopy were
      represented.  CONCLUSION: This proof-of-principle assessment confirms that in
      patients with a history of abdominal surgery the water method significantly
      increases the proportion able to complete unsedated colonoscopy. The water method
      deserves to be evaluated in patients with other factors associated with difficult
      colonoscopy.

PMID- 22586532
TI  - A novel method of endoscopic removal of an impacted ampullary stone using a snare
      (case report with video).

PMID- 22586533
TI  - Endoscopic management of complete colonic obstruction.
AB  - A patient with metastatic rectal cancer underwent a diverting transverse loop
      colostomy due to rectal obstruction. 16 months later, he underwent a low anterior
      resection to resect his rectal cancer along with reversal of his transverse
      colostomy, and creation of a temporary loop ileostomy. Six months later, he was
      brought to the operating room for closure of his ileostomy. Post-operatively, the
      patient developed nausea, vomiting, and abdominal distention and imaging revealed
      a large bowel obstruction, confirmed by colonoscopy. The patient refused surgical
      diversion and a cecostomy tube was placed for decompression. After maturation of
      the cecostomy fistula, a rendezvous colonoscopy was performed, retrograde through
      the rectum and antegrade through the cecostomy fistula. The obstructing mucosa
      was traversed and the site of obstruction was balloon dilated, relieving the
      obstruction endoscopically.

PMID- 22586534
TI  - Contrast enhanced ultrasonography in the diagnosis of IgG4-negative autoimmune
      pancreatitis: A case report.
AB  - Autoimmune pancreatitis (AIP) is a rare disorder frequently manifesting as a mass
      like lesion that may lead to obstructive jaundice. We report here a case of
      pancreatic obstruction with painless jaundice, and elevation of CA 19-9 without
      elevation of serum IgG4. Contrast enhanced ultrasonography (CE US) revealed the
      possibility of AIP, and the final pathological findings confirmed the diagnosis.

PMID- 22586535
TI  - Feasibility of colonoscopy with water infusion in minimally sedated patients in
      an Asian Community Setting.
AB  - BACKGROUND: Investigators in the US described large volume water infusion with
      marked benefits but acknowledged the limitation of male veteran predominance in
      the study subjects. The aim of this study was to assess the feasibility of large
      volume water infusion in Asian patients undergoing minimal sedation diagnostic
      colonoscopy in a community setting.  METHODS: Consecutive patients who underwent
      colonoscopy were randomized to receive large volume (entire colon) (Group A,
      n=51), limited volume (rectum and sigmoid colon) (Group B, n=51) water infusion,
      or air insufflation (Group C, n=51). Pain during insertion, completion rate,
      cecal intubation and total procedure times, and patient satisfaction were
      evaluated. Pain and satisfaction were assessed with a 0-10 visual analog scale. 
      RESULTS: The mean pain scores during insertion were lower in the Group A and
      Group B than in Group C, 3.3+/-2.4, 3.0+/-2.2 and 4.4+/-2.6, respectively
      (p=0.028 and p=0.004). The completion rates and cecal intubation times were
      similar among the three groups. The procedure time was significantly longer in
      Group A than in group C (15.3+/-5.9 min vs. 13.1+/-5.4 min, p=0.049). Overall
      satisfaction with the procedure was greater in Group B than in Group C only
      (9.7+/-0.5 vs. 9.4+/-0.8, p=0.044).  CONCLUSIONS: Diagnostic colonoscopy with
      large volume water infusion without air insufflation appears to be feasible in
      minimally sedated Asian patients in a community setting. Measures to improve the
      outcome further are discussed.

PMID- 22586536
TI  - The water method - untapped potential in extended flexible sigmoidoscopy for
      colorectal cancer screening?

PMID- 22586538
TI  - Treatment of fecal incontinence - review of observational studies (OS) and
      randomized controlled trials (RCT) related to injection of bulking agent into
      peri-anal tissue.
AB  - PURPOSE: Novel treatments are needed to augment medical therapy for fecal
      incontinence.  METHODS: Medline and Google search (fecal incontinence and
      injection treatment), English publications.  RESULTS: Twenty-two observational
      studies and 4 randomized controlled trials were identified. OS mostly with
      limited sample sizes reported promising results. Repeated injection was necessary
      in some patients. Effect on anal sphincter pressures was highly variable.
      Significant improvements in the length of anal high-pressure zone, asymmetry
      index and maximum tolerable rectal volume were suggested. Four randomized
      controlled trials (n=176) revealed: 1. Short-term benefits from injection of
      Bioplastique under ultrasound guidance compared with digital guidance; 2.
      Silicone biomaterial (PTQ) provided some advantages and was safer than carbon
      coated beads (Durasphere); 3. PTQ did not demonstrate clinical benefit compared
      to control injection of saline; 4. There was significant improvement at 6 weeks
      post injection, but no difference between Bulkamid and Permacol. A 2010 Cochrane
      review, however, noted that these data were inconclusive due to limited number
      and methodological weaknesses.  CONCLUSION: Further studies are warranted to
      assess patient-centered outcomes (e.g. adequate relief) in addition to the
      attenuation of severity of incontinence symptoms in ambulatory patients. In
      nursing home residents, cost-effectiveness studies combining injection treatment
      and prompted voiding (to mitigate constraints of immobility and dementia) in
      preventing peri-anal skin complications deserves to be considered.

PMID- 22586537
TI  - Endosonography in solid and cystic pancreatic tumors.
AB  - Pancreatic tumors being either benign or malignant can be solid or cystic.
      Although diverse in presentation, their imaging features share commonalities and
      it is often difficult to distinguish these tumors. Endoscopic ultrasonography
      (EUS) is the most sensitive of the imaging procedures currently available for
      characterizing pancreatic tumors, and is especially good in identifying the
      smaller sized tumors. Additional applications inclusive of EUS-guided fine needle
      aspiration (EUS-FNA) are useful in tissue sampling and preoperative staging of
      pancreatic tumors.Although diagnostic capabilities have greatly evolved with
      advances in EUS and tissue processing technology (cytology, tumor markers, DNA
      analysis), differentiation of benign and malignant neoplasms, neoplastic and non
      neoplastic (chronic pancreatitis) conditions, continues to be challenging.Recent
      innovative applications include contrast-enhanced EUS with Doppler mode, contrast
      enhanced harmonic EUS, 3-dimensinal EUS, and EUS elastography. Incorporation of
      these methods has improved the differential diagnosis of pancreatic tumors.
      Finally, a multi-disciplinary approach involving radiology, gastroenterology and
      surgical specialties is often necessary for accurate diagnosis and management of
      solid and cystic pancreatic tumors.

PMID- 22586540
TI  - Introduction to the volume 2, first issue.

PMID- 22586539
TI  - Meet our Senior Associate Editor: Professor Felix W. Leung.

PMID- 22586541
TI  - Recognition of changes in microvascular and microstructural patterns upon
      magnifying endoscopy predicted the presence of extranodal gastric MALToma.
AB  - BACKGROUND AND OBJECTIVES: Gastric MALToma is difficult to recognize upon
      endoscopy. The aim of this study is to evaluate the application of
      microstructural and microvascular patterns in recognizing gastric MALToma on
      magnifying endoscopy.  METHOD: All patients with diagnosis of gastric MALToma
      upon histology were recruited. They received magnifying endoscopy to observe for
      changes in microstructural and microvascular patterns. For patients with H
      pylori, eradication therapy would be given. For those without, appropriate
      treatments including gastrectomy or chemotherapy were commenced accordingly.
      Patients treated with H pylori eradication and non-operative treatments received
      follow-up magnifying endoscopy, and the same features were observed to predict
      the response to these treatments.  RESULTS: From 2004 to 2007, nine patients
      presented to with epigastric pain, dyspepsia and belching. All patients were
      confirmed to have MALToma upon initial biopsy. Five patients had H pylori
      infection and received eradication. Two patients without H pylori were treated
      with Laparoscopic total gastrectomy. Two patients had pulmonary metastasis and
      treated with chemotherapy. Under magnifying endoscopy, all the lesions
      demonstrated either absence or irregular gastric pits. Moreover, there was
      consistently appearance of spider-shaped vascular pattern. Five patients with H
      pylori eradication had follow-up magnifying endoscopy, four of them showed
      resolution of abnormal vascular pattern and recovery of gastric pits. 
      CONCLUSION: Abnormal spider like vasculature and disappearance of gastric pits
      are diagnostic features upon magnifying endoscopy for gastric MALToma. These
      features enhanced the diagnosis and assessment of extent of involvement during
      primary endoscopy, as well as follow-up surveillance for response to non
      operative treatments.

PMID- 22586542
TI  - Complication rates of colonic polypectomy in relation to polyp characteristics
      and techniques: a district hospital experience.
AB  - BACKGROUND: Colonic polypectomy reduces the subsequent rate of development of
      colonic cancer but is not without its risks. We aimed to examine our complication
      rates in relation to the characteristics of polyps and techniques employed. 
      METHODS: A database for all colonic polypectomies performed over a 31/2-year
      period between 2006 and 2009 was matched against all patients readmitted after an
      endoscopy. Serious complications post-polypectomy were defined as events leading
      to readmission within 14 days.  RESULTS: We performed 2106 polypectomies on 1252
      patients in this period. Fourteen patients or 24 (1.1%) polypectomies experienced
      complications. Two patients (0.09%) experienced perforation, 10 (0.47%) had
      bleeding and 3 (0.14%) had post-polypectomy syndromes. Our bleeding rate was
      1:211, lower than the national standard of 1:100. No deaths were reported.
      Complication rates rose from 1% in the smallest group (1-10 mm) to 4.9% in the
      largest (>31 mm) but the difference was not statistically significant (p=0.067).
      Right-colon polypectomies had a higher tendency of developing post-polypectomy
      syndrome and bleeding (p=0.002). Complication rates in snare polypectomies were
      not significantly different from that of hot biopsies (p=0.64). However,
      endoscopic mucosal resections (EMR) had significantly more complications compared
      to snares (p=0.045) and hot biopsies (p=0.026).  CONCLUSION: We achieved lower
      bleeding rates than that published nationally. Hot biopsies did not carry a
      higher risk unlike EMRs. Although polyp size may be an important risk factor,
      statistical significance was not met. Ascending and transverse colon
      polypectomies carried the highest risks of complications.

PMID- 22586543
TI  - Utility of single balloon enteroscopy (SBE) for difficult cases of total
      colonoscopy.
AB  - Balloon enteroscopy (BE) was originally developed for observation of the deep
      small intestine, and has recently been utilized for difficult cases of total
      colonoscopy due to reasons such as adhesions and elongation. In this report, we
      present our experience with single balloon enteroscopy (SBE) to facilitate
      successful colonoscopy when standard techniques failed. In two cases, early colon
      cancers were detected in the cecum by SBE and were removed endoscopically or
      surgically. A third case is discussed in which SBE was attempted but was
      ultimately not successful. In that case, total colonoscopy was not performed
      because of looping in the sigmoid and transverse colon. A fourth case in which
      SBE was performed in order to remove colonic gas in a patient with megacolon. In
      that case, total colonoscopy could not be completed because the SBE balloon could
      not "grab" the dilated colon and therefore could not advance. SBE is a useful
      adjunct to standard colonoscopy in challenging cases, but has limitations and
      does not always ensure success.

PMID- 22586544
TI  - Retained capsule endoscopy causing intestinal obstruction - Endoscopic retrieval
      by retrograde single-balloon enteroscopy.

PMID- 22586545
TI  - Tapeworm infection identified on capsule endoscopy.

PMID- 22586546
TI  - A pilot study to assess feasibility of the water method to aid colonoscope
      insertion in community settings in the United States.
AB  - BACKGROUND: The water method decreases patient discomfort and sedation
      requirement. Applicability in non-veteran community settings in the United States
      (U.S.) has not been reported.  AIMS: Our aim is to perform a pilot study to
      establish feasibility of use the water method at 2 community sites. We tested the
      hypothesis that compared with air insufflation patients examined with the water
      method would require less sedation without adverse impact on outcomes.  METHODS:
      Two performance improvement projects were carried out. Consecutive patients who
      consented to respond to a questionnaire after colonoscopy were enrolled. Project
      1: The design was single-blinded (patient only); quasi-randomized - odd days
      (water), even days (air). Colonoscopy was performed by a staff attending. Project
      2: A supervised trainee performed the reported procedures. In both, patient
      demographics (age, gender and body mass index), amount of sedation required
      during colonoscopy and procedure-related variables were recorded. The patients
      completed a questionnaire that enquired about discomfort during colonoscopy and
      willingness to repeat the procedure within 24 hours after the procedure. 
      RESULTS: Project 1: Significantly lower doses of fentanyl and midazolam were used
      and a higher adenoma detection rate (ADR) was demonstrated in the water group.
      Project 2: 100% cecal intubation rate was achieved by the supervised trainee. 
      CONCLUSION: This is the first pilot report in the U.S. documenting feasibility of
      the water method as the principal modality to aid colonoscope insertion in both
      male and female community patients. In a head-to-head comparison, significant
      reduction of sedation requirement is confirmed as hypothesized. No adverse impact
      on outcomes was noted.

PMID- 22586547
TI  - Endoscopic ampullectomy: a practical guide.
AB  - Endoscopic ampullectomy is a minimally invasive method of treating superficial
      lesions of the ampulla of Vater. With careful patient selection and lesion
      assessment it is a safe and efficacious therapeutic procedure that can obviate
      the need for potentially major surgical intervention. Strategies for safe and
      successful endoscopic ampullectomy with a focus on resection technique and
      recognition and management of complications are presented.

PMID- 22586548
TI  - How to improve the success of endoscopic ultrasound guided fine needle aspiration
      cytology in the diagnosis of pancreatic lesions.
AB  - Endoscopic ultrasonography (EUS) is highly accurate for assessing the pancreatic
      parenchyma and ductal system. Currently, it is the most sensitive imaging
      procedure for detecting small solid pancreatic masses. EUS-guided fine needle
      aspiration cytology (EUS-FNA) is a safe and highly accurate tool for the
      diagnosis of pancreatic malignancy. Prior to perform an EUS-FNA one should wonder
      whether the benefits outweigh the potential risks of the procedure. Therefore, it
      is important to take into account whether the procedure will influence patient
      management. The diagnostic yield and success rate of EUS-FNA in pancreatic
      lesions varies greatly depending on many factors including: the characteristics
      of the lesion itself (location of the mass and consistency of the lesion),
      technical factors (type of needle size, use of stylet, use of suction and number
      of needle passes performed) and the availability of immediate cytological
      assessment of the specimen. The aim of this review is to analyze all these
      factors for optimizing specimen collection and diagnostic efficiency in dealing
      with solid pancreatic masses.

PMID- 22586549
TI  - The role of upper gastrointestinal endoscopy in treating postoperative
      complications in bariatric surgery.
AB  - There are an estimated 500 million obese individuals worldwide. Currently,
      bariatric surgery has been shown to result in clinically significant weight loss.
      With increasing demand for bariatric surgery, endoscopic techniques used intra
      and postoperatively continue to evolve. Endoscopic evaluation of anastomotic
      integrity following RYGB allows for early detection of anastomotic leaks.
      Furthermore, endoscopy is a valuable tool to diagnose and treat RYGB
      postoperative surgical complications such as anastomotic leakage, hemorrhage and
      stricture formation. Early evidence suggests that endoscopic management of upper
      gastrointestinal hemorrhage following RYGB is effective. In addition, endoscopic
      balloon dilatation is able to effectively treat obstruction in the setting of
      gastrojejunal anastomotic strictures. With successful endoscopic management of
      these complications, bariatric patients may avoid more invasive surgical
      procedures.

PMID- 22586560
TI  - Q&A: Anna Barker on the cancer genome atlas.

PMID- 22586550
TI  - Interventional balloon-enteroscopy.
AB  - Balloon assisted enteroscopy (BE) expands greatly the therapeutic options in
      interventional endoscopy; bleeding sites, strictures, polyps, and other small
      bowel lesions are increasingly been treated by use of BE in the last 10 years.
      Treatment options for small bowel bleeding include Argon plasma coagulation
      (APC), injection therapy, and application of TTS metal clips, and thereby
      bleeding is stopped in most cases. Dilating symptomatic strictures, resecting
      polyps as seen in Peutz-Jeghers syndrome (PJS), and removing foreign bodies, BE
      carries most endoscopic treatment techniques to the small bowel. Another new
      indication field for BE are interventions at the biliary system in patients with
      surgically modified anatomy such as Roux-Y anastomosis. This review offers a full
      overview on indications of BE and refers to the practical use of the method for
      all endoscopic interventions.

PMID- 22586561
TI  - Revamping the clinical trials system.

PMID- 22586568
TI  - Unraveling the role of hypoxia-inducible factor in renal cell carcinoma: a
      biological and therapeutic perspective.
AB  - The genetic control of hypoxia-inducible factor (HIF) has long been associated
      with the pathogenesis of clear cell renal cell carcinoma. Only recently have the
      complex genetics and biology of relevant HIF subtypes been unraveled, leading to
      potential novel strategies for treating this disease.

PMID- 22586569
TI  - Targeting NF-kappaB in mouse models of lung adenocarcinoma.
AB  - Xue et al. demonstrate response and increased survival but development of
      acquired resistance to proteasome and inhibitor-kappaB kinase inhibitors
      targeting NF-kappaB activation in adenocarcinomas of Kras-activated, p53
      deficient mice.

PMID- 22586570
TI  - mTOR inhibition, the second generation: ATP-competitive mTOR inhibitor initiates
      unexpected receptor tyrosine kinase-driven feedback loop.
AB  - mTOR inhibition with the ATP-competitive kinase inhibitor AZD8055 induces
      receptor tyrosine kinase-dependent feedback activation of AKT.

PMID- 22586571
TI  - Functional subtyping of breast cancer.
AB  - Breast cancers can be subdivided in several different ways. In this issue, Brough
      and colleagues describe a functional subtyping of breast cancers based on their
      responses to specific perturbations.

PMID- 22586572
TI  - Parallel anticancer drug development and molecular stratification to qualify
      predictive biomarkers: dealing with obstacles hindering progress.
AB  - Current anticancer drug development still largely follows the classic designs
      developed for chemotherapeutic agents over the past 4 to 5 decades, remaining
      slow, costly, and inefficient, with continuing high risks of costly late drug
      attrition. A Pharmacologic Audit Trail has been described to decrease these
      risks, incorporating pharmacokinetic, pharmacodynamic, intermediate efficacy
      endpoints, as well as patient stratification molecular biomarkers. Molecular
      biomarker-based patient selection in hypothesis-testing early clinical trials is
      critical to clinically qualify putative predictive biomarkers for rationally
      designed, molecularly targeted drugs as early as possible. Nevertheless, major
      concerns have been raised about the impact of using such biomarkers in early
      trials, in view of the costs and time involved to develop multiple certified
      assays for clinical use. The rapid evolution of novel technologies of utility to
      this field, such as next-generation sequencing and circulating tumor-cell
      isolation, makes these valid concerns of critical importance. We therefore
      propose a more efficient parallel predictive biomarker and clinical anticancer
      drug development process to deal with the obstacles hindering progress.

PMID- 22586573
TI  - A shining light in the darkness for the treatment of pancreatic neuroendocrine
      tumors.
AB  - Gastroenteropancreatic neuroendocrine tumors are rare neoplasms; past decades
      have seen limited research channeled into this area. Recently, 2 placebo
      controlled phase III trials using 2 drugs--everolimus and sunitinib--with
      distinct molecular rationales achieved their principal objective of increasing
      survival in patients with advanced pancreatic neuroendocrine tumors (PNET).
      Nonetheless, several questions remain unanswered, notably defining the optimal
      schedule for integrating these targeted agents with conventional cytotoxics and
      other treatment options, and identifying appropriate biomarkers for patients with
      the potential to derive greater benefit. In this article, we analyze the results
      of the 2 largest studies ever completed in patients with PNETs and discuss the
      challenges for future drug development in this setting. SUMMARY: Sunitinib and
      everolimus will become new treatment options for patients with PNETs and will be
      integrated into the complex therapeutic management of this disease. In this
      review, we summarize the evidence-based data of these drugs as well as the
      molecular-based science in this setting that will lay the groundwork for future
      studies.

PMID- 22586574
TI  - Different superstructures formed by Janus-type nucleosides.
AB  - We describe the formation of different superstructures from novel Janus-type
      nucleoside analogues depending on different base pairing patterns in the solution
      state.

PMID- 22586576
TI  - Breast cancer guidelines.

PMID- 22586577
TI  - Breast cancer guidelines.

PMID- 22586579
TI  - Loss of Pdk1-Foxo1 signaling in myeloid cells predisposes to adipose tissue
      inflammation and insulin resistance.
AB  - Chronic inflammation in adipose tissue contributes to obesity-related insulin
      resistance. The 3-phosphoinositide-dependent protein kinase 1 (Pdk1)/forkhead
      transcription factor (Foxo1) pathway is important in regulating glucose and
      energy homeostasis, but little is known about this pathway in adipose tissue
      macrophages (ATMs). To investigate this, we generated transgenic mice that
      carried macrophage/granulocyte-specific mutations, including a Pdk1 knockout
      (LysMPdk1(-/-)), a Pdk1 knockout with transactivation-defective Foxo1
      (Delta256LysMPdk1(-/-)), a constitutively active nuclear (CN) Foxo1
      (CNFoxo1(LysM)), or a transactivation-defective Foxo1 (Delta256Foxo1(LysM)). We
      analyzed glucose metabolism and gene expression in ATM populations isolated with
      fluorescence-activated cell sorting. The LysMPdk1(-/-) mice exhibited elevated M1
      macrophages in adipose tissue and insulin resistance. Overexpression of
      transactivation-defective Foxo1 rescued these phenotypes. CNFoxo1(LysM) promoted
      transcription of the C-C motif chemokine receptor 2 (Ccr2) in ATMs and increased
      M1 macrophages in adipose tissue. On a high-fat diet, CNFoxo1(LysM) mice
      exhibited insulin resistance. Pdk1 deletion or Foxo1 activation in bone marrow
      derived macrophages abolished insulin and interleukin-4 induction of genes
      involved in alternative macrophage activation. Thus, Pdk1 regulated macrophage
      infiltration by inhibiting Foxo1-induced Ccr2 expression. This shows that the
      macrophage Pdk1/Foxo1 pathway is important in regulating insulin sensitivity in
      vivo.

PMID- 22586580
TI  - ZnT8 is a major CD8+ T cell-recognized autoantigen in pediatric type 1 diabetes.
AB  - Type 1 diabetes results from the destruction of beta-cells by an autoimmune T
      cell response assisted by antigen-presenting B cells producing autoantibodies.
      CD8(+) T-cell responses against islet cell antigens, thought to play a central
      role in diabetes pathogenesis, can be monitored using enzyme-linked immunosorbent
      spot (ELISpot) assays. However, such assays have been applied to monitoring of
      adult patients only, leaving aside the large and increasing pediatric patient
      population. The objective of this study was twofold: 1) to develop a CD8(+) T
      cell interferon-gamma ELISpot assay for pediatric patients and 2) to determine
      whether zinc transporter 8 (ZnT8), a recently described target of autoantibodies
      in a majority of patients, is also recognized by autoreactive CD8(+) T cells.
      Using DNA immunization of humanized mice, we identified nine HLA-A2-restricted
      ZnT8 epitopes. Among 36 HLA-A2(+) children with diabetes, 29 responded to ZnT8
      epitopes, whereas only 3 of 16 HLA-A2(+) control patients and 0 of 17 HLA-A2(-)
      control patients responded. Some single ZnT8 epitopes performed as well as the
      group of epitopes in discriminating between patients and control individuals.
      Thus, ZnT8 is a major CD8(+) T-cell autoantigen, and ELISpot assays display
      similar performance in adult and pediatric type 1 diabetes.

PMID- 22586581
TI  - Hyperglycemia causes renal cell damage via CCN2-induced activation of the TrkA
      receptor: implications for diabetic nephropathy.
AB  - CCN2, a secreted profibrotic protein, is highly expressed in diabetic nephropathy
      (DN) and implicated in its pathogenesis; however, the actions of CCN2 in DN
      remain elusive. We previously demonstrated that CCN2 triggers signaling via
      tropomyosin receptor kinase A (TrkA). Trace expression of TrkA is found in normal
      kidneys, but its expression is elevated in several nephropathies; yet its role in
      DN is unexplored. In this study we show de novo expression of TrkA in human and
      murine DN. We go on to study the molecular mechanisms leading to TrkA activation
      and show that it involves hypoxia, as demonstrated by ischemia-reperfusion injury
      and in vitro experiments mimicking hypoxia, implicating hypoxia as a common
      pathway leading to disease. We also expose renal cells to hyperglycemia, which
      led to TrkA phosphorylation in mesangial cells, tubular epithelial cells, and
      podocytes but not in glomerular endothelial cells and renal fibroblasts. In
      addition, we report that hyperglycemia caused an induction of phosphorylated
      extracellular signal-related kinase 1/2 and Snail1 that was abrogated by
      silencing of TrkA or CCN2 using small interfering RNA. In conclusion, we provide
      novel evidence that TrkA is activated in diabetic kidneys and suggest that anti
      TrkA therapy may prove beneficial in DN.

PMID- 22586583
TI  - Uncoupling endothelial nitric oxide synthase is ameliorated by green tea in
      experimental diabetes by re-establishing tetrahydrobiopterin levels.
AB  - The current study investigated the potential of green tea (GT) to improve
      uncoupling of endothelial nitric oxide synthase (eNOS) in diabetic conditions. In
      rats with streptozotocin-induced diabetes, nitric oxide (NO) bioavailability was
      reduced by uncoupling eNOS, characterized by a reduction in tetrahydrobiopterin
      (BH(4)) levels and a decrease in the eNOS dimer-to-monomer ratio. GT treatment
      ameliorated these abnormalities. Moreover, immortalized human mesangial cells
      (ihMCs) exposed to high glucose (HG) levels exhibited a rise in reactive oxygen
      species (ROS) and a decline in NO levels, which were reversed with GT. BH(4) and
      the activity of guanosine triphosphate cyclohydrolase I decreased in ihMCs
      exposed to HG and was normalized by GT. Exogenous administration of BH(4) in
      ihMCs reversed the HG-induced rise in ROS and the decline in NO production.
      However, coadministration of GT with BH(4) did not result in a further reduction
      in ROS production, suggesting that reduced ROS with GT was indeed secondary to
      uncoupled eNOS. In summary, GT reversed the diabetes-induced reduction of BH(4)
      levels, ameliorating uncoupling eNOS, and thus increasing NO bioavailability and
      reducing oxidative stress, two abnormalities that are involved in the
      pathogenesis of diabetic nephropathy.

PMID- 22586582
TI  - Inhibition of gelatinase B (matrix metalloprotease-9) activity reduces cellular
      inflammation and restores function of transplanted pancreatic islets.
AB  - Islet transplantation provides an approach to compensate for loss of insulin
      producing cells in patients with type 1 diabetes. However, the intraportal route
      of transplantation is associated with instant inflammatory reactions to the graft
      and subsequent islet destruction as well. Although matrix metalloprotease (MMP)-2
      and -9 are involved in both remodeling of extracellular matrix and leukocyte
      migration, their influence on the outcome of islet transplantation has not been
      characterized. We observed comparable MMP-2 mRNA expressions in control and
      transplanted groups of mice, whereas MMP-9 mRNA and protein expression levels
      increased after islet transplantation. Immunostaining for CD11b (Mac-1)
      expressing leukocytes (macrophage, neutrophils) and Ly6G (neutrophils) revealed
      substantially reduced inflammatory cell migration into islet-transplanted liver
      in MMP-9 knockout recipients. Moreover, gelatinase inhibition resulted in a
      significant increase in the insulin content of transplanted pancreatic islets and
      reduced macrophage and neutrophil influx compared with the control group. These
      results indicate that the increase of MMP-9 expression and activity after islet
      transplantation is directly related to enhanced leukocyte migration and that
      early islet graft survival can be improved by inhibiting MMP-9 (gelatinase B)
      activity.

PMID- 22586584
TI  - Modulation of redox balance leaves murine diabetogenic TH1 T cells "LAG-3-ing"
      behind.
AB  - Preventing activation of diabetogenic T cells is critical for delaying type 1
      diabetes onset. The inhibitory molecule lymphocyte activation gene 3 (LAG-3) and
      metalloprotease tumor necrosis factor-alpha converting enzyme (TACE) work
      together to regulate TH1 responses. The aim of this study was to determine if
      regulating redox using a catalytic antioxidant (CA) could modulate TACE-mediated
      LAG-3 shedding to impede diabetogenic T-cell activation and progression to
      disease. A combination of in vitro experiments and in vivo analyses using NOD
      mouse strains was conducted to test the effect of redox modulation on LAG-3
      shedding, TACE enzymatic function, and disease onset. Systemic treatment of NOD
      mice significantly delayed type 1 diabetes onset. Disease prevention correlated
      with decreased activation, proliferation, and effector function of diabetogenic T
      cells; reduced insulin-specific T-cell frequency; and enhanced LAG-3(+) cells.
      Redox modulation also affected TACE activation, diminishing LAG-3 cleavage.
      Furthermore, disease progression was monitored by measuring serum soluble LAG-3,
      which decreased in CA-treated mice. Therefore, affecting redox balance by CA
      treatment reduces the activation of diabetogenic T cells and impedes type 1
      diabetes onset via decreasing T-cell effector function and LAG-3 cleavage.
      Moreover, soluble LAG-3 can serve as an early T-cell-specific biomarker for type
      1 diabetes onset and immunomodulation.

PMID- 22586585
TI  - A gene-family analysis of 61 genetic variants in the nicotinic acetylcholine
      receptor genes for insulin resistance and type 2 diabetes in American Indians.
AB  - Cigarette smoking is a risk factor for type 2 diabetes. Genetic variants in the
      nicotinic acetylcholine receptor (nAChR) genes have been associated with smoking
      phenotypes and are likely to influence diabetes. Although each single variant may
      have only a minor effect, the joint contribution of multiple single nucleotide
      polymorphisms (SNPs) to the occurrence of disease may be larger. In this study,
      we conducted a gene-family analysis to investigate the joint impact of 61 tag
      SNPs in 7 nAChRs genes on insulin resistance and type 2 diabetes in 3,665
      American Indians recruited by the Strong Heart Family Study. Results show that
      although multiple SNPs showed marginal individual association with insulin
      resistance and type 2 diabetes, only a few can pass adjustment for multiple
      testing. However, a gene-family analysis considering the joint impact of all 61
      SNPs reveals significant association of the nAChR gene family with both insulin
      resistance and type 2 diabetes (both P < 0.0001), suggesting that genetic
      variants in the nAChR genes jointly contribute to insulin resistance and type 2
      diabetes among American Indians. The effects of these genetic variants on insulin
      resistance and diabetes are independent of cigarette smoking per se.

PMID- 22586586
TI  - Oxidation of fatty acids is the source of increased mitochondrial reactive oxygen
      species production in kidney cortical tubules in early diabetes.
AB  - Mitochondrial reactive oxygen species (ROS) cause kidney damage in diabetes. We
      investigated the source and site of ROS production by kidney cortical tubule
      mitochondria in streptozotocin-induced type 1 diabetes in rats. In diabetic
      mitochondria, the increased amounts and activities of selective fatty acid
      oxidation enzymes is associated with increased oxidative phosphorylation and net
      ROS production with fatty acid substrates (by 40% and 30%, respectively), whereas
      pyruvate oxidation is decreased and pyruvate-supported ROS production is
      unchanged. Oxidation of substrates that donate electrons at specific sites in the
      electron transport chain (ETC) is unchanged. The increased maximal production of
      ROS with fatty acid oxidation is not affected by limiting the electron flow from
      complex I into complex III. The maximal capacity of the ubiquinol oxidation site
      in complex III in generating ROS does not differ between the control and diabetic
      mitochondria. In conclusion, the mitochondrial ETC is neither the target nor the
      site of ROS production in kidney tubule mitochondria in short-term diabetes.
      Mitochondrial fatty acid oxidation is the source of the increased net ROS
      production, and the site of electron leakage is located proximal to coenzyme Q at
      the electron transfer flavoprotein that shuttles electrons from acyl-CoA
      dehydrogenases to coenzyme Q.

PMID- 22586587
TI  - Ceramide mediates vascular dysfunction in diet-induced obesity by PP2A-mediated
      dephosphorylation of the eNOS-Akt complex.
AB  - Vascular dysfunction that accompanies obesity and insulin resistance may be
      mediated by lipid metabolites. We sought to determine if vascular ceramide leads
      to arterial dysfunction and to elucidate the underlying mechanisms.
      Pharmacological inhibition of de novo ceramide synthesis, using the Ser palmitoyl
      transferase inhibitor myriocin, and heterozygous deletion of dihydroceramide
      desaturase prevented vascular dysfunction and hypertension in mice after high-fat
      feeding. These findings were recapitulated in isolated arteries in vitro,
      confirming that ceramide impairs endothelium-dependent vasorelaxation in a tissue
      autonomous manner. Studies in endothelial cells reveal that de novo ceramide
      biosynthesis induced protein phosphatase 2A (PP2A) association directly with the
      endothelial nitric oxide synthase (eNOS)/Akt/Hsp90 complex that was concurrent
      with decreased basal and agonist-stimulated eNOS phosphorylation. PP2A attenuates
      eNOS phosphorylation by preventing phosphorylation of the pool of Akt that
      colocalizes with eNOS and by dephosphorylating eNOS. Ceramide decreased the
      association between PP2A and the predominantly cytosolic inhibitor 2 of PP2A. We
      conclude that ceramide mediates obesity-related vascular dysfunction by a
      mechanism that involves PP2A-mediated disruption of the eNOS/Akt/Hsp90 signaling
      complex. These results provide important insight into a pathway that represents a
      novel target for reversing obesity-related vascular dysfunction.

PMID- 22586588
TI  - ChREBP mediates glucose-stimulated pancreatic beta-cell proliferation.
AB  - Glucose stimulates rodent and human beta-cell replication, but the intracellular
      signaling mechanisms are poorly understood. Carbohydrate response element-binding
      protein (ChREBP) is a lipogenic glucose-sensing transcription factor with unknown
      functions in pancreatic beta-cells. We tested the hypothesis that ChREBP is
      required for glucose-stimulated beta-cell proliferation. The relative expression
      of ChREBP was determined in liver and beta-cells using quantitative RT-PCR (qRT
      PCR), immunoblotting, and immunohistochemistry. Loss- and gain-of-function
      studies were performed using small interfering RNA and genetic deletion of ChREBP
      and adenoviral overexpression of ChREBP in rodent and human beta-cells.
      Proliferation was measured by 5-bromo-2'-deoxyuridine incorporation,
      [(3)H]thymidine incorporation, and fluorescence-activated cell sorter analysis.
      In addition, the expression of cell cycle regulatory genes was measured by qRT
      PCR and immunoblotting. ChREBP expression was comparable with liver in mouse
      pancreata and in rat and human islets. Depletion of ChREBP decreased glucose
      stimulated proliferation in beta-cells isolated from ChREBP(-/-) mice, in INS-1
      derived 832/13 cells, and in primary rat and human beta-cells. Furthermore,
      depletion of ChREBP decreased the glucose-stimulated expression of cell cycle
      accelerators. Overexpression of ChREBP amplified glucose-stimulated proliferation
      in rat and human beta-cells, with concomitant increases in cyclin gene
      expression. In conclusion, ChREBP mediates glucose-stimulated proliferation in
      pancreatic beta-cells.

PMID- 22586589
TI  - Intranasal insulin suppresses food intake via enhancement of brain energy levels
      in humans.
AB  - Cerebral insulin exerts anorexic effects in humans and animals. The underlying
      mechanisms, however, are not clear. Because insulin physiologically facilitates
      glucose uptake by most tissues of the body and thereby fosters intracellular
      energy supply, we hypothesized that intranasal insulin reduces food consumption
      via enhancement of the neuroenergetic level. In a double-blind, placebo
      controlled, within-subject comparison, 15 healthy men (BMI 22.2 +/- 0.37 kg/m(2))
      aged 22-28 years were intranasally administered insulin (40 IU) or placebo after
      an overnight fast. Cerebral energy metabolism was assessed by (31)P magnetic
      resonance spectroscopy. At 100 min after spray administration, participants
      consumed ad libitum from a test buffet. Our data show that intranasal insulin
      increases brain energy (i.e., adenosine triphosphate and phosphocreatine levels).
      Cerebral energy content correlates inversely with subsequent calorie intake in
      the control condition. Moreover, the neuroenergetic rise upon insulin
      administration correlates with the consecutive reduction in free-choice calorie
      consumption. Brain energy levels may therefore constitute a predictive value for
      food intake. Given that the brain synchronizes food intake behavior in dependence
      of its current energetic status, a future challenge in obesity treatment may be
      to therapeutically influence cerebral energy homeostasis. Intranasal insulin,
      after optimizing its application schema, seems a promising option in this regard.

PMID- 22586599
TI  - Q&A: Stephen Baylin and Peter Jones on team science by Suzanne Rose.

PMID- 22586590
TI  - Reactive oxygen species signaling facilitates FOXO-3a/FBXO-dependent vascular BK
      channel beta1 subunit degradation in diabetic mice.
AB  - Activity of the vascular large conductance Ca(2+)-activated K(+) (BK) channel is
      tightly regulated by its accessory beta(1) subunit (BK-beta(1)). Downregulation
      of BK-beta(1) expression in diabetic vessels is associated with upregulation of
      the forkhead box O subfamily transcription factor-3a (FOXO-3a)-dependent F-box
      only protein (FBXO) expression. However, the upstream signaling regulating this
      process is unclear. Overproduction of reactive oxygen species (ROS) is a common
      finding in diabetic vasculopathy. We hypothesized that ROS signaling cascade
      facilitates the FOXO-3a/FBXO-mediated BK-beta(1) degradation and leads to
      diabetic BK channel dysfunction. Using cellular biology, patch clamp, and
      videomicroscopy techniques, we found that reduced BK-beta(1) expression in
      streptozotocin (STZ)-induced diabetic mouse arteries and in human coronary smooth
      muscle cells (SMCs) cultured with high glucose was attributable to an increase in
      protein kinase C (PKC)-beta and NADPH oxidase expressions and accompanied by
      attenuation of Akt phosphorylation and augmentation of atrogin-1 expression.
      Treatment with ruboxistaurin (a PKCbeta inhibitor) or with GW501516 (a peroxisome
      proliferator-activated receptor delta activator) reduced atrogin-1 expression and
      restored BK channel-mediated coronary vasodilation in diabetic mice. Our results
      suggested that oxidative stress inhibited Akt signaling and facilitated the FOXO
      3a/FBXO-dependent BK-beta(1) degradation in diabetic vessels. Suppression of the
      FOXO-3a/FBXO pathway prevented vascular BK-beta(1) degradation and protected
      coronary function in diabetes.

PMID- 22586600
TI  - Nanoparticle theories slowly turn into practice.

PMID- 22586591
TI  - Methazolamide is a new hepatic insulin sensitizer that lowers blood glucose in
      vivo.
AB  - We previously used Gene Expression Signature technology to identify methazolamide
      (MTZ) and related compounds with insulin sensitizing activity in vitro. The
      effects of these compounds were investigated in diabetic db/db mice, insulin
      resistant diet-induced obese (DIO) mice, and rats with streptozotocin (STZ)
      induced diabetes. MTZ reduced fasting blood glucose and HbA(1c) levels in db/db
      mice, improved glucose tolerance in DIO mice, and enhanced the glucose-lowering
      effects of exogenous insulin administration in rats with STZ-induced diabetes.
      Hyperinsulinemic-euglycemic clamps in DIO mice revealed that MTZ increased
      glucose infusion rate and suppressed endogenous glucose production. Whole-body or
      cellular oxygen consumption rate was not altered, suggesting MTZ may inhibit
      glucose production by different mechanism(s) to metformin. In support of this,
      MTZ enhanced the glucose-lowering effects of metformin in db/db mice. MTZ is
      known to be a carbonic anhydrase inhibitor (CAI); however, CAIs acetazolamide,
      ethoxyzolamide, dichlorphenamide, chlorthalidone, and furosemide were not
      effective in vivo. Our results demonstrate that MTZ acts as an insulin sensitizer
      that suppresses hepatic glucose production in vivo. The antidiabetic effect of
      MTZ does not appear to be a function of its known activity as a CAI. The additive
      glucose-lowering effect of MTZ together with metformin highlights the potential
      utility for the management of type 2 diabetes.

PMID- 22586601
TI  - Chinese, American researchers expand collaborations.

PMID- 22586608
TI  - On the road to combinations of targeted therapies: PPM1H phosphatase as a
      suppressor of trastuzumab resistance.
AB  - Lee-Hoeflich and colleagues use RNA interference screening to identify the
      serine/threonine phosphatase PPM1H as an inhibitor of trastuzumab resistance in
      vitro. This finding extends the molecular portrait of trastuzumab-resistant cells
      and provides a rationale when searching for potential therapeutic targets among
      regulators of PPM1H and/or its substrates.

PMID- 22586609
TI  - The potential benefits of BIM in the further pursuit of biomarker discovery in
      cancer therapeutics.
AB  - In this issue of Cancer Discovery, Faber and colleagues demonstrate that the
      basal expression of BIM is positively correlated with the amount of apoptosis
      induced by the corresponding tyrosine kinase inhibitor treatment within the same
      subtype of several oncogene-addicted cancer cell types. Their results suggest
      that pre-treatment assessment of BIM levels can identify patients who would
      benefit from molecularly targeted therapies even after biomarker-based patient
      selection.

PMID- 22586619
TI  - Q&A: Phillip Sharp on biomedical convergence.
AB  - Upgrading therapeutics calls for tighter links across scientific and engineering
      disciplines.

PMID- 22586610
TI  - Discovery of Mdm2-MdmX E3 ligase inhibitors using a cell-based ubiquitination
      assay.
AB  - E3 ubiquitin ligases are of interest as drug targets for their ability to
      regulate protein stability and function. The oncogene Mdm2 is an attractive E3
      ligase to target, as it is the key negative regulator of the tumor suppressor
      p53, which controls the transcription of genes involved in cell fate.
      Overexpression of Mdm2 facilitates tumorigenesis by inactivating p53, and through
      p53-independent oncogenic effects. We developed a high-throughput cellular Mdm2
      auto-ubiquitination assay, which we used to discover a class of small-molecule
      Mdm2 ligase activity inhibitors. These compounds inhibit Mdm2 and p53
      ubiquitination in cells, reduce viability of cells with wild-type p53, and
      synergize with DNA-damaging agents to cause cell death. We determined that these
      compounds effectively inhibit the E3 ligase activity of the Mdm2-MdmX hetero
      complex. This mechanism may be exploitable to create a new class of anti-tumor
      agents.

PMID- 22586620
TI  - Drugs, diagnostic tests approved quickly.
AB  - Accelerated review and greater understanding of tumor biology speed targeted
      treatments to patients.

PMID- 22586611
TI  - PPM1H is a p27 phosphatase implicated in trastuzumab resistance.
AB  - The HER2 oncogene is overexpressed or amplified in 20% of breast cancers. HER2
      positive cancer historically portends a poor prognosis, but the HER2-targeted
      therapy trastuzumab mitigates this otherwise ominous distinction. Nevertheless,
      some patients suffer disease recurrence despite trastuzumab, and metastatic
      disease remains largely incurable due to innate and acquired resistance. Thus,
      understanding trastuzumab resistance remains an unmet medical need. Through RNA
      interference screening, we discovered that knockdown of the serine/threonine
      phosphatase PPM1H confers trastuzumab resistance via reduction in protein levels
      of the tumor suppressor p27. PPM1H dephosphorylates p27 at threonine 187, thus
      removing a signal for proteasomal degradation. We further determined that
      patients whose tumors express low levels of PPM1H trend towards worse clinical
      outcome on trastuzumab. Identifying PPM1H as a novel p27 phosphatase reveals new
      insight into how cancer cells destabilize a well-recognized tumor suppressor.
      Furthermore, low PPM1H expression may identify a subset of HER2-positive tumors
      that are harder to treat.

PMID- 22586621
TI  - Speed traps for trials.
AB  - Around the globe, investigators struggle to expedite clinical research.

PMID- 22586628
TI  - The prospects of HPV vaccination in cervical cancer prevention: results of a new
      independent trial.
AB  - Herrero and colleagues show that in a phase III randomized trial in Guanacaste,
      Costa Rica, the use of a human papillomavirus type 16 (HPV16) and HPV18 ASO4
      adjuvanted vaccine (Cervarix) resulted in complete efficacy against 12-month
      persistent HPV16 and HPV18 infections and partial protection against HPV31, 33,
      and 45 in HPV-naive young women ages 18 to 25.

PMID- 22586629
TI  - Nuclear receptor LXR as a novel therapeutic antitumoral target in glioblastoma.
AB  - Both primary and transformed cells need cholesterol for their growth. Guo and
      colleagues unraveled the connection between epidermal growth factor receptor
      mutations in glioblastoma and increased cholesterol influx via sterol regulatory
      element-binding protein 1 and low-density lipoprotein receptor (LDLR) increase.
      They propose the activation of the liver X receptor-inducible degrader of LDLR
      LDLR axis as a therapeutic approach to reduce intracellular cholesterol, block
      tumor growth, and induce cell death.

PMID- 22586630
TI  - Forty years of translational cancer research.
AB  - Forty years after the signing of the National Cancer Act, we have produced a
      stunning repository of scientific information that is being translated into
      better therapies for patients. Although challenges remain, many solutions have
      been adopted, leading to early signs of progress against some of humankind's most
      dreadful diseases. This Prospective attempts to highlight some of the approaches
      that have been successful and analyze some that have not, and peers into a future
      in which renewal of the investment in cancer research will produce further
      benefits for patients.

PMID- 22586639
TI  - Q&A: Michael Stratton on what's next in sequence.

PMID- 22586640
TI  - Broadening recruitment for minorities, the elderly.

PMID- 22586632
TI  - Variants in inflammation genes are implicated in risk of lung cancer in never
      smokers exposed to second-hand smoke.
AB  - Lung cancer in lifetime never smokers is distinct from that in smokers, but the
      role of separate or overlapping carcinogenic pathways has not been explored. We
      therefore evaluated a comprehensive panel of 11,737 single-nucleotide
      polymorphisms (SNP) in inflammatory-pathway genes in a discovery phase (451 lung
      cancer cases, 508 controls from Texas). SNPs that were significant were evaluated
      in a second external population (303 cases, 311 controls from the Mayo Clinic).
      An intronic SNP in the ACVR1B gene, rs12809597, was replicated with significance
      and restricted to those reporting adult exposure to environmental tobacco smoke.
      Another promising candidate was an SNP in NR4A1, although the replication OR did
      not achieve statistical significance. ACVR1B belongs to the TGFR-beta
      superfamily, contributing to resolution of inflammation and initiation of airway
      remodeling. An inflammatory microenvironment (second-hand smoking, asthma, or hay
      fever) is necessary for risk from these gene variants to be expressed. These
      findings require further replication, followed by targeted resequencing, and
      functional validation.

PMID- 22586631
TI  - Prevention of persistent human papillomavirus infection by an HPV16/18 vaccine: a
      community-based randomized clinical trial in Guanacaste, Costa Rica.
AB  - Target groups for human papillomavirus (HPV) vaccination are controversial. We
      evaluated vaccine efficacy (VE) against 1-year persistent infection, stratified
      by age and sexual behavior, among young women in Costa Rica. We randomized 7,466
      healthy women 18 to 25 years of age to HPV16/18 or hepatitis A vaccine (follow
      up, 50.4 months). According-to-protocol (ATP) cohorts included compliant HPV
      negative women; intention-to-treat (ITT) included all randomized women. ATP VE
      was 90.9% (95% CI, 82.0-95.9) against HPV16/18 infections, 44.5% against
      HPV31/33/45 (95% CI, 17.5-63.1), and 12.4% (95% CI, -3.2 to 25.6) against any
      oncogenic infection. Overall ITT VE against HPV16/18 infections was 49.0%, but
      ATP and ITT VE almost reached 100% in year 4 of follow-up. ATP efficacy against
      HPV16/18 was similar by age, but ITT VE was greatest among youngest women (68.9%
      among those 18-19 years of age; 21.8% among those 24-25 years of age) and 79.8%
      among virgins. Among previously unexposed women, vaccination is highly
      efficacious against HPV16/18 and partially against HPV31/33/45. Vaccination is
      most effective in women and girls before they initiate sexual activity, with
      programmatic and individual decision implications.

PMID- 22586641
TI  - Placing bets on biotech.

PMID- 22586648
TI  - Understanding the lethal variant of prostate cancer: power of examining extremes.
AB  - Small cell prostate carcinoma is a lethal variant of castration-resistant
      prostate cancer. Beltran and colleagues identified overexpression and
      amplification of both aurora kinase A (AURKA) and the MYCN proto-oncogene in the
      small cell prostate carcinomas and propose Aurora kinase A as a potential
      therapeutic target in this disease subset.

PMID- 22586650
TI  - HER2 signaling and resistance to the anti-EGFR monoclonal antibody cetuximab: a
      further step toward personalized medicine for patients with colorectal cancer.
AB  - Primary and acquired resistance to anti-epidermal growth factor receptor (EGFR)
      drugs are clinically relevant problems in patients with metastatic colorectal
      carcinoma. A complex network of molecular alterations is involved in this
      phenomenon. Bertotti et al. report the development of serially transplantable
      groups of tumor xenografts in immune-deficient mice from patient-derived,
      genetically characterized metastatic colorectal carcinoma samples. These
      experimental models ("xenopatients") might represent a novel approach to discover
      and characterize the mechanisms of resistance to anti-EGFR therapy and other
      molecularly targeted therapies in metastatic colorectal carcinoma. In this
      respect, Bertotti et al. were able to identify HER2 gene amplification as one
      such mechanism of resistance to anti-EGFR therapy.

PMID- 22586649
TI  - NF-kappaB in cancer: a matter of life and death.
AB  - Activation of NF-kappaB has been linked to various cellular processes in cancer,
      including inflammation, transformation, proliferation, angiogenesis, invasion,
      metastasis, chemoresistance, and radioresistance. Although acute inflammation
      mediates innate and humoral immunity, chronic inflammation has been linked to
      tumorigenesis. Thus, inhibition of NF-kappaB has therapeutic potential in
      sensitization of tumors to chemotherapeutic agents; however, generalized
      suppression of NF-kappaB can result in serious host toxicity with minimum effect
      on the tumor.

PMID- 22586651
TI  - mTORC 2:1 for chemotherapy sensitization in glioblastoma.
AB  - mTOR signaling is frequently deregulated in cancer, including brain tumors.
      Although the signaling of mTOR complex 1 (mTORC1) has been subject to intensive
      investigations and mTORC1 itself has been a well-established cancer drug target
      for years, the role of the second complex, mTORC2, remains elusive. Tanaka et al.
      reveal an EGFRvIII-mTORC2-NFkappaB signaling cascade and demonstrate that mTORC2
      mediates cisplatin resistance through NF-kappaB in an Akt-independent manner in
      glioblastoma. Uncovering the role of mTORC2 in chemotherapy resistance in
      glioblastoma highlights the need for further investigations of mTORC2 inhibition.

PMID- 22586652
TI  - Curing "incurable" cancer.
AB  - Cancer cells are preferentially killed by anticancer agents because key signals
      for growth and cell division are "always on" as opposed to the alternative "on"
      and "off" signaling of normal cells. Too much of today's anticancer drug
      discovery effort may go toward reversing genetically promoted "always on"
      signals. More effective anticancer drug targets may be found through use of RNAi
      technologies that pinpoint the key gene regulatory and metabolic weakness of the
      "always on" cancer cells.

PMID- 22586658
TI  - What's cost-effective in cancer care?

PMID- 22586653
TI  - A molecularly annotated platform of patient-derived xenografts ("xenopatients")
      identifies HER2 as an effective therapeutic target in cetuximab-resistant
      colorectal cancer.
AB  - Only a fraction of patients with metastatic colorectal cancer receive clinical
      benefit from therapy with anti-epidermal growth factor receptor (EGFR)
      antibodies, which calls for the identification of novel biomarkers for better
      personalized medicine. We produced large xenograft cohorts from 85 patient
      derived, genetically characterized metastatic colorectal cancer samples
      ("xenopatients") to discover novel determinants of therapeutic response and new
      oncoprotein targets. Serially passaged tumors retained the morphologic and
      genomic features of their original counterparts. A validation trial confirmed the
      robustness of this approach: xenopatients responded to the anti-EGFR antibody
      cetuximab with rates and extents analogous to those observed in the clinic and
      could be prospectively stratified as responders or nonresponders on the basis of
      several predictive biomarkers. Genotype-response correlations indicated HER2
      amplification specifically in a subset of cetuximab-resistant,
      KRAS/NRAS/BRAF/PIK3CA wild-type cases. Importantly, HER2 amplification was also
      enriched in clinically nonresponsive KRAS wild-type patients. A proof-of-concept,
      multiarm study in HER2-amplified xenopatients revealed that the combined
      inhibition of HER2 and EGFR induced overt, long-lasting tumor regression. Our
      results suggest promising therapeutic opportunities in cetuximab-resistant
      patients with metastatic colorectal cancer, whose medical treatment in the
      chemorefractory setting remains an unmet clinical need. SIGNIFICANCE: Direct
      transfer xenografts of tumor surgical specimens conserve the interindividual
      diversity and the genetic heterogeneity typical of the tumors of origin,
      combining the flexibility of preclinical analysis with the informative value of
      population-based studies. Our suite of patient-derived xenografts from metastatic
      colorectal carcinomas reliably mimicked disease response in humans, prospectively
      recapitulated biomarker-based case stratification, and identified HER2 as a
      predictor of resistance to anti-epidermal growth factor receptor antibodies and
      of response to combination therapies against HER2 and epidermal growth factor
      receptor in this tumor setting.

PMID- 22586659
TI  - Making molecular diagnostics ready for prime time.

PMID- 22586672
TI  - Q&A: William Sellers on success in small molecules. Interview by Eric Bender.

PMID- 22586673
TI  - Upcoming battles in the war on cancer.

PMID- 22586678
TI  - Anti-MET targeted therapy has come of age: the first durable complete response
      with MetMAb in metastatic gastric cancer.
AB  - The MET/hepatocyte growth factor (HGF) signaling pathway plays important roles in
      oncogenesis and tumor progression in a variety of human cancers. MET/HGF drives
      an invasive signaling program that can be dysregulated in human cancers through a
      number of activating mechanisms, including mutations, overexpression,
      amplification, alternative splicing, and HGF ligand-induced autocrine/paracrine
      loop signaling. As a testimony of MET-targeting therapeutics is beginning to come
      to clinical fruition, Catenacci and colleagues report the first case of durable
      complete response under an anti-MET receptor monoclonal antibody, MetMAb, in a
      patient with chemotherapy-refractory, advanced gastric cancer metastatic to the
      liver, found to have high MET gene polysomy and remarkably high serum HGF level.
      Serum and tissue studies also revealed predictive biomarkers for therapeutic
      response to MET inhibition.

PMID- 22586679
TI  - Genomic investigation of dedifferentiated liposarcoma suggests a role for
      therapeutic targeting of the tumor epigenome.
AB  - A comprehensive genetic analysis of dedifferentiated liposarcomas suggests that
      epigenetic modifications are common and may alter the differentiation capacity in
      these tumors. Furthermore, these data suggest that treatment strategies aimed at
      altering histone acetylation and/or DNA methylation are worthy of further study.

PMID- 22586680
TI  - A combined epigenetic therapy equals the efficacy of conventional chemotherapy in
      refractory advanced non-small cell lung cancer.
AB  - A new study by Juergens and colleagues provides the first successful example of a
      combined epigenetic therapy capable of achieving results similar to those of
      conventional chemotherapy in refractory metastatic non-small cell lung cancer.
      Furthermore, the authors describe interesting blood-based DNA methylation
      biomarkers that may be useful in predicting clinical response.

PMID- 22586681
TI  - PI3Kdelta inhibitors in cancer: rationale and serendipity merge in the clinic.
AB  - Several phosphoinositide 3-kinase (PI3K) inhibitors are in the clinic and many
      more are in preclinical development. CAL-101, a selective inhibitor of the
      PI3Kdelta isoform, has shown remarkable success in certain hematologic
      malignancies. Although PI3Kdelta signaling plays a central role in lymphocyte
      biology, the degree of single-agent therapeutic activity of CAL-101 during early
      phase development has been somewhat unexpected. CAL-101 works in part by blocking
      signals from the microenvironment that normally sustain leukemia and lymphoma
      cells in a protective niche. As PI3Ks enter the arena of molecular-targeted
      therapies, CAL-101 provides proof of principle that isoform-selective compounds
      can be effective in selected cancer types and patient populations. SIGNIFICANCE:
      A key question is whether compounds targeting a single PI3K catalytic isoform can
      provide meaningful single agent efficacy in cancer cells that express multiple
      isoforms. Clinical studies of the drug CAL-101 have provided a significant
      advance by showing that selective targeting of PI3Kdelta achieves efficacy in
      chronic lymphocytic leukemia, in part through targeting the tumor
      microenvironment.

PMID- 22586689
TI  - Analyzing intact proteins with mass spectrometry.
AB  - A new top-down method of identifying intact proteins is particularly suited to
      differentiating highly related protein species created by alternative splicing,
      proteolytic events, and post-translational modifications.

PMID- 22586682
TI  - Combination epigenetic therapy has efficacy in patients with refractory advanced
      non-small cell lung cancer.
AB  - Epigenetic alterations are strongly associated with the development of cancer. We
      conducted a phase I/II trial of combined epigenetic therapy with azacitidine and
      entinostat, inhibitors of DNA methylation and histone deacetylation,
      respectively, in extensively pretreated patients with recurrent metastatic non
      small cell lung cancer. This therapy is well tolerated, and objective responses
      were observed, including a complete response and a partial response in a patient
      who remains alive and without disease progression approximately 2 years after
      completing protocol therapy. Median survival in the entire cohort was 6.4 months
      (95% CI 3.8-9.2), comparing favorably with existing therapeutic options.
      Demethylation of a set of 4 epigenetically silenced genes known to be associated
      with lung cancer was detectable in serial blood samples in these patients and was
      associated with improved progression-free (P = 0.034) and overall survival (P =
      0.035). Four of 19 patients had major objective responses to subsequent
      anticancer therapies given immediately after epigenetic therapy. SIGNIFICANCE:
      This study demonstrates that combined epigenetic therapy with low-dose
      azacitidine and entinostat results in objective, durable responses in patients
      with solid tumors and defines a blood-based biomarker that correlates with
      clinical benefit.

PMID- 22586690
TI  - Triple-acting drug boosts prostate cancer survival.
AB  - A phase III trial of the agent MDV3100 in men with advanced prostate cancer
      previously treated with docetaxel-based chemotherapy is being stopped early so
      that the drug can be given to all participants.

PMID- 22586683
TI  - Amplification of CRKL induces transformation and epidermal growth factor receptor
      inhibitor resistance in human non-small cell lung cancers.
AB  - We previously identified a region of recurrent amplification on chromosome
      22q11.21 in a subset of primary lung adenocarcinomas. Here we show that CRKL,
      encoding for an adaptor protein, is amplified and overexpressed in non-small cell
      lung cancer (NSCLC) cells that harbor 22q11.21 amplifications. Overexpression of
      CRKL in immortalized human airway epithelial cells promoted anchorage-independent
      growth and tumorigenicity. Oncogenic CRKL activates the SOS1-RAS-RAF-ERK and SRC
      C3G-RAP1 pathways. Suppression of CRKL in NSCLC cells that harbor CRKL
      amplifications induced cell death. Overexpression of CRKL in epidermal growth
      factor receptor (EGFR)-mutant cells induces resistance to gefitinib by activating
      extracellular signal-regulated kinase and AKT signaling. We identified CRKL
      amplification in an EGFR inhibitor-treated lung adenocarcinoma that was not
      present before treatment. These observations demonstrate that CRKL overexpression
      induces cell transformation, credential CRKL as a therapeutic target for a subset
      of NSCLC that harbor CRKL amplifications, and implicate CRKL as an additional
      mechanism of resistance to EGFR-directed therapy. SIGNIFICANCE: These studies
      credential CRKL as an oncogene in a subset of NSCLC. Overexpression of CRKL
      induces cell transformation and resistance to epidermal growth factor receptor
      inhibitor treatment and suggest that therapeutic interventions targeting CRKL may
      confer a clinical benefit in a defined subset of NSCLCs.

PMID- 22586691
TI  - Automated pathology gives accurate predictions.
AB  - Image-processing software has successfully predicted survival of breast cancer
      patients based on microscopy images of tissue samples. The Stanford University
      researchers hope that computerized pathology eventually will provide more
      objective, reproducible tumor grading in the clinic.

PMID- 22586692
TI  - Phenotypic profiling identifies novel anticancer drugs.
AB  - Image analysis of vasculature in a tumor-derived 3D matrix shows high predictive
      value in discovering angiogenesis inhibitors.

PMID- 22586693
TI  - HDAC inhibitors show benefits in breast cancer.
AB  - One agent reduces tamoxifen resistance in preclinical studies, while lysine
      acetylation measurements may monitor clinical benefit of a second drug.

PMID- 22586694
TI  - FDA pulls approval for avastin in breast cancer.
AB  - The FDA has revoked approval of the breast cancer indication for bevacizumab
      (Avastin; Genetech), saying that studies have not shown enough of a benefit to
      outweigh the drug's serious and potentially life-threatening side effects.

PMID- 22586699
TI  - Paget's disease of the bone after treatment with Denosumab: a case report.
AB  - Bone affection in Paget's disease is characterized by increased bone turnover
      localised at one or more sites of the skeleton. Bisphosphonates are the drugs of
      choice when treating the increased bone turnover in Paget's disease. However, in
      cases of decreased kidney function only less effective treatments that are
      available as bisphosphonates are contraindicated in these patients. We present a
      case of a male patient aged 86 years with GFR of 11 mL/min and Paget's disease
      successfully treated by Denosumab. The bone turnover and pain decreased upon
      treatment.

PMID- 22586701
TI  - The buccal gland of Lampetra japonica is a source of diverse bioactive proteins.
AB  - The parasitic phase lampreys (Lampetra japonica) are bloodsuckers in the marine,
      and their buccal gland secretion (lamphredin) contains various regulators such as
      anticoagulants, ion channel blockers, and immune suppressors like those from
      leeches, insects, ticks, vampire bats, and snakes. This review focuses on the
      functions and characteristics of the active proteins from the buccal gland of L.
      japonica for the first time, and provides new insights into the parasitic
      mechanisms of lampreys and the possibilities of developing drugs such as novel
      anticoagulants, thrombolytic agents, local anesthetics, and immunosuppressants.

PMID- 22586700
TI  - Absence of bone sialoprotein (BSP) impairs primary bone formation and resorption:
      the marrow ablation model under PTH challenge.
AB  - Bone sialoprotein (BSP) is highly expressed in early bone deposition and may play
      a part in primary bone mineralization. We previously showed that while BSP-/-
      mice have a mild secondary bone phenotype and are responsive to mechanical
      (unloading) and hormonal (ovariectomy, parathyroid hormone (PTH)) challenges,
      repair of a cortical bone defect, which involves primary bone deposition is
      significantly delayed in these mice. In the present study, we investigated the
      role of BSP in a pure model of primary bone modeling. Bone marrow was ablated by
      trans-epiphysis aspiration in the femora of BSP+/+ and BSP-/- mice, and 7 days
      post surgery MUCT analysis showed vigorous new bone formation in the shaft of
      BSP+/+ animals but much less in BSP-/- mice. After 14 days, the volume of
      medullary bone was significantly decreased as expected in BSP+/+ mice, while it
      remained stable in the BSP-/-. Osteoid thickness and surface were higher in BSP-/
      at day 7, suggesting delayed mineralization, while osteoclast surface and number
      were significantly lower at day 14, a stage of high medullary bone resorption. At
      day 7, mRNA expression of early osteoblast marker genes (RUNX2, osterix, alkaline
      phosphatase, osteopontin) did not differ between the two genotypes, while markers
      of terminal differentiation (MEPE, DMP1, osteocalcin) as well as receptor
      activator of NF-kappaB ligand (RANKL) and tartrate-resistant acid phosphatase
      (TRAP) were significantly lower in BSP-/- than in BSP+/+ mice. PTH treatment
      maintained the volume of medullary bone up to 12 days after ablation in BSP+/+
      mice, but failed to do so in BSP-/- mice. PTH significantly increased bone
      formation rate in both genotype, while it reduced osteoclast number and surface
      in BSP+/+, but not in BSP-/- medullary bone. In summary, medullary bone formation
      after marrow ablation is blunted in BSP-/- mice, with delayed resorption and
      impaired response to PTH. These findings confirm the hypothesis of a crucial role
      for BSP in primary ossification, which has long been suspected for
      mineralization, but here extends to bone deposition and turnover.

PMID- 22586702
TI  - Different sensitivity of H69 modification enzymes RluD and RlmH to mutations in
      Escherichia coli 23S rRNA.
AB  - Nucleoside modifications are introduced into the ribosomal RNA during the
      assembly of the ribosome. The number and the localization of the modified
      nucleosides in rRNAs are known for several organisms. In bacteria, rRNA modified
      nucleosides are synthesized by a set of specific enzymes, the majority of which
      have been identified in Escherichia coli. Each rRNA modification enzyme
      recognizes its substrate nucleoside(s) at a specific stage of ribosome assembly.
      Not much is known about the specificity determinants involved in the substrate
      recognition of the modification enzymes. In order to shed light on the substrate
      specificity of RluD and RlmH, the enzymes responsible for the introduction of
      modifications into the stem-loop 69 (H69), we monitored the formation of H69
      pseudouridines (Psi) and methylated pseudouridine (m3Psi) in vitro on ribosomes
      with alterations in 23S rRNA. While the synthesis of Psis in H69 by RluD is
      relatively insensitive to the point mutations at neighboring positions,
      methylation of one of the Psis by RlmH exhibited a much stronger sensitivity.
      Apparently, in spite of synthesizing modifications in the same region or even at
      the same position of rRNA, the two enzymes employ different substrate recognition
      mechanisms.

PMID- 22586703
TI  - Consequences of the presence of 24-epibrassinolide, on cultures of a diatom,
      Asterionella formosa.
AB  - Addition of the plant hormone 24-epibrassinolide to culture media stimulated the
      growth of a freshwater diatom, Asterionella formosa. The hormone stimulated
      activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a key enzyme from
      Calvin cycle, by 6-fold. Other key metabolic enzymes, phosphofructokinase and
      malate dehydrogenase were also stimulated but to a lesser extent. The activity of
      glucose-6-phosphate dehydrogenase, involved in the oxidative pentose phosphate
      pathway, also increased in the presence of the hormone but only under non
      reducing conditions. In cells stimulated by epibrassinolide, activated enzymes
      were sensitive to oxidized-DTT. GAPDH purified from cells grown in the presence
      of the hormone was not associated with a small protein of 8.5 kDa shown to be
      similar to CP12. Consequently the activity of GAPDH was no longer regulated by
      either oxidizing or reducing conditions. Among enzymes that, like GAPDH,
      responded positively to reducing agent were fructose-1,6-bisphosphatase (FBPase)
      and glucose-6-phosphate dehydrogenase (G6PDH). These enzymes were also sensitive
      to, and were negatively regulated by, oxidized-DTT. The activities in extracts
      from illuminated cells differed from those from darkened cells: FBPase, G6PDH and
      GAPDH, that were activated by DTT in darkened cells were no more activated in
      illuminated cells, but were oxidized by oxidized-DTT. Thus, oxidizing or reducing
      conditions mimic the conditions in dark and light, respectively. Unlike the other
      enzymes, phosphofructokinase (PFK) was inhibited by DTT but oxidized-DTT reversed
      this effect. The enzymes shown to be redox regulated in vitro by
      reduction/oxidation are very likely candidates for regulation in vivo by
      thioredoxins.

PMID- 22586704
TI  - Kinetic and thermodynamic characterization of the functional properties of a
      hybrid versatile peroxidase using isothermal titration calorimetry: Insight into
      manganese peroxidase activation and lignin peroxidase inhibition.
AB  - Isothermal titration calorimetry (ITC) was developed for measuring lignin
      peroxidase (LiP) and manganese peroxidase (MnP) activities of versatile
      peroxidase (VP) from Bjerkandera adusta. Developing an ITC approach provided an
      alternative to colorimetric methods that enabled reaction kinetics to be
      accurately determined. Although VP from Bjerkandera adjusta is a hybrid enzyme,
      specific conditions of [Mn+2] and pH were defined that limited activity to either
      LiP or MnP activities, or enabled both to be active simultaneously. MnP activity
      was found to be more efficient than LiP activity, with activity increasing with
      increasing concentrations of Mn+2. These properties of MnP were explained by a
      second metal binding site involved in homotropic substrate (Mn+2) activation. The
      activation of MnP was also accompanied by a decrease in both activation energy
      and substrate (Mn) affinity, reflecting a flexible enzyme structure. In contrast
      to MnP activity, LiP activity was inhibited by high dye (substrate)
      concentrations arising from uncompetitive substrate inhibition caused by
      substrate binding to a site distinct from the catalytic site. Our study provides
      a new level of understanding about the mechanism of substrate regulation of
      catalysis in VP from B. adjusta, providing insight into a class of enzyme, hybrid
      class II peroxidases, for which little experimental data is available.

PMID- 22586705
TI  - ATP independent proteasomal degradation of NQO1 in BL cell lines.
AB  - Human NAD(P)H: quinone oxidoreductase 1 (NQO1) catalyzes the obligatory two
      electron reduction of quinones. For this peculiar catalytic mechanism, the enzyme
      is considered an important cytoprotector. The NQO1 gene is expressed in all human
      tissues, unless a polymorphism due to C609T point mutation is present. This
      polymorphism produces a null phenotype in the homozygous condition and reduced
      enzyme activity in the heterozygous one. We previously demonstrated that two cell
      lines of haematopoietic origin, HL60 and Raji cells, possess the same
      heterozygous genotype, but different phenotypes; as expected for a heterozygous
      condition the HL60 cell line showed a low level of enzyme activity, while the
      Raji cell line appeared as null phenotype. The level of NQO1 mRNA was similar in
      the two cell lines and the different phenotype was not due to additional
      mutations or to expression of alternative splicing products. Here we show that in
      Raji BL cell line with heterozygous genotype the null NQO1 phenotype is due to
      20S proteasome degradation of wild type and mutant protein isoforms and is not
      directly linked to C609T polymorphism. This finding may have important
      implications in B-cell differentiation, in leukaemia risk evaluation and in
      chemotherapy based on proteasome inhibitors.

PMID- 22586706
TI  - Alternative splicing generates two lactate dehydrogenase subunits differentially
      expressed during hypoxia via HIF-1 in the shrimp Litopenaeus vannamei.
AB  - Metabolic adjustment to low oxygen exposure (hypoxia) in the white shrimp
      Litopenaeus vannamei implies a shift to anaerobic metabolism. Lactate
      dehydrogenase (LDH) is a key enzyme of the anaerobic metabolism described in most
      organisms. The structure and expression of the LDH gene, as well as the LDH
      isoenzymes in marine crustacean are not well defined. In the present study we
      characterized a gene that codes for two LDH subunits, measured their expression
      and detected the isoenzymes in tissues from white shrimp. We also silenced the
      transcriptional activator hypoxia inducible factor 1 (HIF-1) to elucidate the
      regulation of LDH in tissues from white shrimp in response to hypoxia. The
      complete LDH gene coding sequence is 7571 bp (LvanLDH) and encodes two different
      LDH subunits (LDHvan-1 and LDHvan-2) generated by alternative splicing and
      composed of 332 amino acids with conserved domains important for the function and
      regulation. Phylogenetic analysis shows that LvanLDH -1 and -2 are closer to the
      invertebrate counterparts. The LDHvan-1 transcript increased 2.5-fold after
      hypoxia in gills but not in hepatopancreas, while the LDHvan-2 transcript
      decreased 14-fold in muscle but not in gills and hepatopancreas. Three bands with
      LDH activity of ~60-90 kDa were detected in hepatopancreas, while one band of
      ~140 kDa was detected in gills and muscle. The silencing of HIF-1 blocked the
      increase of LDH mRNA and activity produced by hypoxia in gills. These results
      demonstrate a single gene for LDH (LvanLDH) that by alternative splicing
      generates two different LDH subunits (LDHvan-1 and LDHvan-2) that are expressed
      in a tissue-specific manner during hypoxia via the HIF-1 pathway.

PMID- 22586707
TI  - European health-care systems: a new CardioPulse series.

PMID- 22586708
TI  - The United Kingdom's response to the CardioPulse survey questionnaire.

PMID- 22586709
TI  - Prior psychiatric hospitalization: an underappreciated risk factor for premature
      mortality among individuals with chest pain.

PMID- 22586710
TI  - Reorganizing children's heart surgery in England.

PMID- 22586711
TI  - Webinars: the future of online medical education?

PMID- 22586712
TI  - Heart disease in women: I: pathophysiology and symptoms.

PMID- 22586714
TI  - William R. Harvey: an appreciation.

PMID- 22586713
TI  - Hmx1 is required for the normal development of somatosensory neurons in the 
      geniculate ganglion.
AB  - Hmx1 is a variant homeodomain transcription factor expressed in the developing
      sensory nervous system, retina, and craniofacial mesenchyme. Recently, mutations
      at the Hmx1 locus have been linked to craniofacial defects in humans, rats, and
      mice, but its role in nervous system development is largely unknown. Here we show
      that Hmx1 is expressed in a subset of sensory neurons in the cranial and dorsal
      root ganglia which does not correspond to any specific sensory modality. Sensory
      neurons in the dorsal root and trigeminal ganglia of Hmx1dm/dm mouse embryos have
      no detectable Hmx1 protein, yet they undergo neurogenesis and express sensory
      subtype markers normally, demonstrating that Hmx1 is not globally required for
      the specification of sensory neurons from neural crest precursors. Loss of Hmx1
      expression has no obvious effect on the early development of the trigeminal (V),
      superior (IX/X), or dorsal root ganglia neurons in which it is expressed, but
      results in marked defects in the geniculate (VII) ganglion. Hmx1dm/dm mouse
      embryos possess only a vestigial posterior auricular nerve, and general
      somatosensory neurons in the geniculate ganglion are greatly reduced by mid
      gestation. Although Hmx1 is expressed in geniculate neurons prior to cell cycle
      exit, it does not appear to be required for neurogenesis, and the loss of
      geniculate neurons is likely to be the result of increased cell death. Fate
      mapping of neural crest-derived tissues indicates that Hmx1-expressing
      somatosensory neurons at different axial levels may be derived from either the
      neural crest or the neurogenic placodes.

PMID- 22586715
TI  - The metabotropic glutamate 2/3 receptor antagonist LY341495 differentially
      affects recognition memory in rats.
AB  - Experimental evidence suggests that metabotropic glutamate 2/3 (mGlu2/3) receptor
      antagonists affect cognitive function, although contradictory findings have been
      reported. To clarify the role of mGlu2/3 receptor antagonists in one aspect of
      cognition, the present study investigated the effects of a broad range of doses
      of the mGlu2/3 receptor antagonist LY341495 on post-training recognition memory
      components (storage and/or retrieval) in rats. The efficacy of LY341495 in
      antagonizing the extinction of recognition memory was also investigated. The
      novel object recognition test was used as the memory test. The highest LY341495
      doses administered (0.3, 1, and 3 mg/kg) disrupted performance in this
      recognition memory procedure in rats at all delay conditions tested, whereas
      administration of lower doses (0.05 and 0.1 mg/kg) did not impair recognition
      memory. Moreover, administration of the low LY341495 doses (0.05 and 0.1 mg/kg)
      counteracted the extinction of recognition memory. The present results indicate
      that administration of the mGlu2/3 receptor antagonist LY341495 can either impair
      or enhance recognition memory in rats, depending on the dose of the compound and
      delay period used. Thus, together with previously reported findings, the present
      data suggest complex effects of this compound on cognitive function, particularly
      recognition memory.

PMID- 22586717
TI  - FDA maps out global strategy.

PMID- 22586716
TI  - Association between locomotor response to novelty and light reinforcement:
      sensory reinforcement as a rodent model of sensation seeking.
AB  - BACKGROUND: The human personality trait of sensation seeking (SS) indicates an
      attraction to novel sensations and experiences, and is associated with greater
      likelihood of drug abuse. In rodents, locomotor activity in a novel environment
      (Loco) has been found to predict drug self-administration (SA), and has been
      hypothesized to be a translational model of human SS. Previously, we reported
      (Gancarz et al., 2011) that high responder (HR) animals responded more than low
      responder (LR) animals to produce a response contingent light onset. The primary
      goal of this paper was a detailed analysis of the association between Loco and
      light contingent responding in a large sample of rats (n = 93). METHODS: Male
      rats were pre-exposed to dark operant test chambers for ten 30 min sessions and
      baseline levels of responding (snout poking) were determined. The pre-exposure
      phase was followed by 6 sessions during which active responding produced a visual
      sensory reinforcer (VSR; 5 s light onset) according to a variable interval 1 min
      schedule of reinforcement. After completion of the VSR phase, Loco was tested.
      RESULTS: The activating effects (total responding) of light were associated with
      Loco, but the response guiding effects (proportion of active responding) of the
      light were not. In addition, HR rats habituated more slowly in both the VSR and
      Loco tests than LR rats. CONCLUSIONS: These data indicate that VSR measures
      aspects of the rodent's response to novel sensations and experiences that are not
      detected by Loco. These data provide some evidence for the use of light
      reinforcement as an animal model of SS.

PMID- 22586718
TI  - Texas stem cell rules may impede clinical research.

PMID- 22586719
TI  - Spanish health cuts could create "humanitarian problem".

PMID- 22586720
TI  - Military coup triggers health crisis in northern Mali.

PMID- 22586721
TI  - Jean-Francois Champollion and ancient Egyptian embalming.

PMID- 22586722
TI  - Multidisciplinary and collaborative research in sports physiology and
      performance.

PMID- 22586723
TI  - A delay mathematical model for the spread and control of water borne diseases.
AB  - A non-linear SIRS mathematical model to explore the dynamics of water borne
      diseases like cholera is proposed and analyzed by incorporating delay in using
      disinfectants to control the disease. It is assumed that the only way for the
      spread of infection is ingestion of contaminated water by susceptibles. As the
      pathogens discharged by infectives reach to the aquatic environment, it is
      assumed that the growth rate of pathogens is proportional to the number of
      infectives. Further, it is assumed that disinfectants are introduced to kill
      pathogens with a rate proportional to the density of pathogens in the aquatic
      environment. The model is analyzed by using stability theory of delay
      differential equations. It is found that the model exhibits two equilibria, the
      disease free equilibrium and the endemic equilibrium. The analysis shows that
      under certain conditions, the cholera disease may be controlled by using
      disinfectants but a longer delay in their use may destabilize the system.
      Numerical simulation is also carried out to confirm the analytical results.

PMID- 22586724
TI  - A model for transit time distributions through organs that accounts for fractal
      heterogeneity.
AB  - It has been shown that density functions of organ transit time distributions of
      vascular markers (washout curves) are characterized by a power-law tail,
      reflecting the fractal nature of the vascular network. Yet, thus far, no closed
      form model is available that can be fitted to such organ outflow data. Here we
      propose a model that accounts for the existing data. The model is a continuous
      mixture of inverse Gaussian densities, implying flow heterogeneity in the organ.
      It has been fitted to outflow data from the rabbit heart and rat liver. The power
      law decay with exponent -3 observed in the heart, corresponds to an intra-organ
      flow distribution with a relative dispersion of about 35%.

PMID- 22586725
TI  - Ecological importance of the thermal emissivity of avian eggshells.
AB  - Breeding birds have to divide their time between egg incubation and foraging.
      Particularly in cases when only one parent incubates the eggs, and especially in
      cold climates, the cooling of the eggs during absence from the nest may be
      problematic. In the present study we find that the thermal emissivity of
      eggshells may be ecologically important, and that an evolutionary pressure
      towards lower emissivity for exposed eggs in cold climates exists. We plan to
      experimentally compare emissivities among species in a future study.

PMID- 22586726
TI  - Kinetics of peptide secondary structure conversion during amyloid beta-protein
      fibrillogenesis.
AB  - Amyloid fibrils are a common component in many debilitating human neurological
      diseases such as Alzheimer's (AD), Parkinson's, and Creutzfeldt-Jakob, and in
      animal diseases such as BSE. The role of fibrillar Alphabeta proteins in AD has
      stimulated interest in the kinetics of Alphabeta fibril formation. Kinetic models
      that include reaction pathways and rate parameters for the various stages of the
      process can be helpful towards understanding the dynamics on a molecular level.
      Based upon experimental data, we have developed a mathematical model for the
      reaction pathways and determined rate parameters for peptide secondary structural
      conversion and aggregation during the entire fibrillogenesis process from random
      coil to mature fibrils, including the molecular species that accelerate the
      conversions. The model and the rate parameters include different molecular
      structural stages in the nucleation and polymerization processes and the
      numerical solutions yield graphs of concentrations of different molecular species
      versus time that are in close agreement with experimental results. The model also
      allows for the calculation of the time-dependent increase in aggregate size. The
      calculated results agree well with experimental results, and allow differences in
      experimental conditions to be included in the calculations. The specific steps of
      the model and the rate constants that are determined by fitting to experimental
      data provide insight on the molecular species involved in the fibril formation
      process.

PMID- 22586727
TI  - [Treating chronic hepatitis B: what to do and how to do].

PMID- 22586728
TI  - Insight into pressure drop dependent efficiencies of dry powder inhalers.
AB  - PURPOSE: The purpose of this study was to assess the effectiveness of three
      commercial capsule-based dry powder passive inhalers [Rotahaler(r) (RH), Monodose
      Inhaler(r) (MI) and Handihaler(r) (HH)] in de-agglomerating salbutamol sulphate
      (SS) and micronized lactose (LH300) powders and their sensitivity to air flow
      rate changes and air flow resistance. METHODS: Aerosolisation was assessed in
      real-time using a laser diffraction method: this approach was possible as only
      single-component formulations were tested. Volume percent of the aerosolised
      particles with diameter less than 5.4 MUm at air flow rates from 30 to 180 l min
      1 was obtained with the RH, MI and HH and provided a parameter, relative de
      agglomeration (RD), as a measure of de-agglomeration. The pressure drops across
      the device at various flow rates were obtained from a differential pressure
      meter. RESULTS: The relationship between RD of SS and LH300 and air flow rate
      appeared substantially different between the devices. It was surprisingly found
      that in some cases RD dropped at the highest air flows: this indicates a device
      specific maxima in RD occurs, and this may in part be attributed to changes in
      capsule motion. It is proposed that this relationship between RD and pressure
      drop provides a patient focussed simple way to assess RD performance. This
      assessment indicated that MI was the most efficient relative de-agglomerator at
      lower pressure drops, while HH increases its effectiveness at higher pressure
      drops. CONCLUSION: The approach of measuring RD as a function of pressure drop
      revealed instructive variations in the aerosolisation performances of different
      devices. This new approach helps compare device performances with different
      powders, and hence improve optimisation and consistency of performance.

PMID- 22586729
TI  - [Optimized strategy: new concept in antiviral therapy for chronic hepatitis B].

PMID- 22586730
TI  - [Therapy for chronic hepatitis B: can we reject combination therapy].

PMID- 22586731
TI  - [Nucleos(t)ides analog block HBV mother-to-child transmission in pregnancy HBV
      carriers-agreement and challenges].

PMID- 22586734
TI  - [Hungarian Karavukovo from 1751-70].

PMID- 22586735
TI  - [Aggressive anti-Semitism in Austrian sports    in the interwar years: selected
      examples of manifestations and reactions].

PMID- 22586732
TI  - Dynamics and ordering of lipid spin-labels along the coexistence curve of two
      membrane phases: an ESR study.
AB  - An analysis of electron spin resonance (ESR) spectra from compositions along the
      liquid-ordered (L(o)) and liquid-disordered (L(d)) coexistence curve from the
      brain-sphingomyelin/dioleoylphosphatidylcholine/cholesterol (SPM/DOPC/Chol) model
      lipid system was performed to characterize the dynamic structure on a molecular
      level of these coexisting phases. We obtained 200 continuous-wave ESR spectra
      from glycerophospholipid spin-labels labeled at the 5, 7, 10, 12, 14, and 16
      carbon positions of the 2nd acyl chain, a sphingomyelin spin-label labeled at the
      14 carbon position of the amide-linked acyl chain, a headgroup-labeled
      glycerophospholipid, a headgroup-labeled sphingomyelin, and the cholesterol
      analogue spin-label cholestane all within multi-lamellar vesicle suspensions at
      room temperature. The spectra were analyzed using the MOMD (microscopic-order
      macroscopic-disorder) model to provide the rotational diffusion rates and order
      parameters which characterize the local molecular dynamics in these phases. The
      analysis also incorporated the known critical point and invariant points of the
      neighboring three-phase triangle along the coexistence curve. The variation in
      the molecular dynamic structures of coexisting L(o) and L(d) compositions as one
      moves toward the critical point is discussed. Based on these results, a molecular
      model of the L(o) phase is proposed incorporating the "condensing effect" of
      cholesterol on the phospholipid acyl chain dynamics and ordering and the
      "umbrella model" of the phospholipid headgroup dynamics and ordering.

PMID- 22586736
TI  - [The great Chinese famine, 1958-61: introduction to the "descent" into the
      inferno].

PMID- 22586737
TI  - [Famine in the Landle: the long end of    World War I in Vorarlberg, 1918-21].

PMID- 22586739
TI  - ["One has not even enough bread!" Nutrition and morale in the Gau of Tyrol
      Vorarlberg, 1942-43].

PMID- 22586740
TI  - [For "Aryans" only: the visual genesis of the male physique in National
      Socialism].

PMID- 22586741
TI  - [Propaganda and soccer: sports and    politics in the meetings of the Italian
      Azzurri and the Weissen from Vienna in    the interwar years].

PMID- 22586742
TI  - [Operation Bergius "Food from Wood": prestige project of the famine years 1945
      46].

PMID- 22586744
TI  - [The murder of Jews as an educational goal? The place of "worldview education" by
      the SS and police in the framework of the Final Solution].

PMID- 22586745
TI  - [The 24 November 1933 law on habitual criminals: Nazi criminal law    between a
      tradition of reform and racial reorientation].

PMID- 22586746
TI  - ["The year of horrors": a debate on the past in Latvia].

PMID- 22586748
TI  - [Solitude and freedom, the    beginnings of academic education for women - the
      Swedish example].

PMID- 22586749
TI  - Exploration and Exploitation of Data in Bioinformatics.

PMID- 22586750
TI  - [Knowledge in the plural. For a 'generous' history of science].
AB  - Even if C.P. Snow's sharp distinction between a scientific and a literary culture
      has often been contested, historians still mostly conceive these cultures as two
      separate fields. The authors of this article argue that the potential scope of
      the history of science is regrettably limited by this dichotomy. Recent
      developments within the history of science have made clear that scholars of both
      'cultures' share workplaces, practices and self-images to a large extent, and
      that even natural scientists heavily rely on artistic representations. The
      recognition of these commonalities can contribute to a full integration of the
      human sciences into the history of science and, more generally, into cultural
      history. This evolution is further stimulated by the transdisciplinary approach
      which has recently become dominant within the history of the human sciences
      itself. Since the newly founded journal takes part in these fruitful tendencies,
      the authors welcome Studium as a promising enterprise.

PMID- 22586751
TI  - [A beautiful cow is a good cow. Dutch scientists and commercial breeders on
      cattle breeding, 1900-1950].
AB  - In the agricultural journal De Nieuwe Veldbode of 1941 Dutch scientists,
      agricultural engineers, commercial cattle breeders and herd-book officials
      engaged in a prolonged debate about cattle breeding methods. Geneticist Arend
      Hagedoorn started the debate by accusing commercial breeders of deceiving their
      buyers. In his view, breeders were merely interested in producing beautiful show
      bulls that could be sold for high prices, and they ignored the animals'
      hereditary potential for milk production. Rational breeding, he argued, required
      progeny testing: only the production of his daughters should decide on a bull's
      merits. Commercial breeders denied the charge. They did indeed select for
      conformation, not however for aesthetic reasons, but to safeguard the health and
      durability of the breed. In their view, selecting for production was not feasible
      in practice and would, moreover, lead to the degeneration of the breed. In this
      article I explore the backgrounds of this debate by investigating the different
      views of scientists and practical breeders on theory and practice of cattle
      breeding in the first half of the century. I shall show that to understand the
      different viewpoints, the practical realities of dairy farming under Dutch
      circumstances, commercial considerations and normative ideas on good farming have
      to be taken into account.

PMID- 22586752
TI  - [Introduction].
AB  - Along with the international trends in history of computing, Dutch contributions
      over the past twenty years moved away from a focus on machinery to the broader
      scope of use of computers, appropriation of computing technologies in various
      traditions, labour relations and professionalisation issues, and, lately,
      software. It is only natural that an emerging field like computer science sets
      out to write its genealogy and canonise the important steps in its intellectual
      endeavour. It is fair to say that a historiography diverging from such "home"
      interest, started in 1987 with the work of Eda Kranakis--then active in The
      Netherlands--commissioned by the national bureau for technology assessment, and
      Gerard Alberts, turning a commemorative volume of the Mathematical Center into a
      history of the same institute. History of computing in The Netherlands made a
      major leap in the spring of 1994 when Dirk de Wit, Jan van den Ende and Ellen van
      Oost defended their dissertations, on the roads towards adoption of computing
      technology in banking, in science and engineering, and on the gender aspect in
      computing. Here, history of computing had already moved from machines to the use
      of computers. The three authors joined Gerard Alberts and Onno de Wit in
      preparing a volume on the rise of IT in The Netherlands, the sequel of which in
      now in preparation in a team lead by Adrienne van den Bogaard. Dutch research
      reflected the international attention for professionalisation issues (Ensmenger,
      Haigh) very early on in the dissertation by Ruud van Dael, Something to do with
      computers (2001) revealing how occupations dealing with computers typically
      escape the pattern of closure by professionalisation as expected by the, thus
      outdated, sociology of professions. History of computing not only takes use and
      users into consideration, but finally, as one may say, confronts the
      technological side of putting the machine to use, software, head on. The
      groundbreaking works of the 2000 Paderborn meeting and by Martin Campbell-Kelly
      resonate in work done in The Netherlands and recently in a major research project
      sponsored by the European Science Foundation: Software for Europe. The four
      contributions to this issue offer a true cross-section of ongoing history of
      computing in The Netherlands. Gerard Alberts and Huub de Beer return to the
      earliest computers at the Mathematical Center. As they do so under the
      perspective of using the machines, the result is, let us say, remarkable.
      Adrienne van den Bogaard compares the styles of software as practiced by Van der
      Poel and Dijkstra: so much had these two pioneers in common, so different the
      consequences they took. Frank Veraart treats us with an excerpt from his recent
      dissertation on the domestication of the micro computer technology: appropriation
      of computing technology is shown by the role of intermediate actors. Onno de Wit,
      finally, gives an account of the development, prior to internet, of a national
      data communication network among large scale users and its remarkable persistence
      under competition with new network technologies.

PMID- 22586753
TI  - [AERA. Dream machines and computing practices at the Mathematical Center].
AB  - Dream machines may be just as effective as the ones materialised. Their symbolic
      thrust can be quite powerful. The Amsterdam 'Mathematisch Centrum' (Mathematical
      Center), founded February 11, 1946, created a Computing Department in an effort
      to realise its goal of serving society. When Aad van Wijngaarden was appointed as
      head of the Computing Department, however, he claimed space for scientific
      research and computer construction, next to computing as a service. Still, the
      computing service following the five stage style of Hartree's numerical analysis
      remained a dominant characteristic of the work of the Computing Department. The
      high level of ambition held by Aad van Wijngaarden lead to ever renewed
      projections of big automatic computers, symbolised by the never-built AERA. Even
      a machine that was actually constructed, the ARRA which followed A.D. Booth's
      design of the ARC, never made it into real operation. It did serve Van
      Wijngaarden to bluff his way into the computer age by midsummer 1952. Not until
      January 1954 did the computing department have a working stored program computer,
      which for reasons of policy went under the same name: ARRA. After just one other
      machine, the ARMAC, had been produced, a separate company, Electrologica, was set
      up for the manufacture of computers, which produced the rather successful X1
      computer. The combination of ambition and absence of a working machine lead to a
      high level of work on programming, way beyond the usual ideas of libraries of
      subroutines. Edsger W. Dijkstra in particular led the way to an emphasis on the
      duties of the programmer within the pattern of numerical analysis. Programs
      generating programs, known elsewhere as autocoding systems, were at the
      'Mathematisch Centrum' called 'superprograms'. Practical examples were usually
      called a 'complex', in Dutch, where in English one might say 'system'.
      Historically, this is where software begins. Dekker's matrix complex, Dijkstra's
      interrupt system, Dijkstra and Zonneveld's ALGOL compiler--which for housekeeping
      contained 'the complex'--were actual examples of such super programs. In 1960
      this compiler gave the Mathematical Center a leading edge in the early
      development of software.

PMID- 22586754
TI  - [Styles of programming 1952-1972].
AB  - In the field of history of computing, the construction of the early computers has
      received much scholarly attention. However, these machines have not only been
      important because of their logical design and their engineering, but also because
      of the programming practices that emerged around these first machines. This
      article compares two styles of programming that developed around Dutch 'first
      computers'. The first style is represented by Edsger Wybe Dijkstra (1930-2002),
      who would receive the Turing Award for his work in 1972. Dijkstra developed a
      mathematical style of programming--a program was something you should be able to
      design mathematically and prove it logically. The second style is represented by
      Willem Louis van der Poel (born 1926). For him, programming is 'trickology'. A
      program is primarily a technical artefact that should work: a program is
      something you play with, comparable to the way one solves a puzzle.

PMID- 22586755
TI  - [Dutch computer domestication, 1975-1990].
AB  - A computer seems an indispensable tool among twenty-first century households.
      Computers however, did not come as manna from heaven. The domestication and
      appropriation of computers in Dutch households was a result of activities by
      various intermediary actors. Computers became household commodities only
      gradually. Technophile computer hobbyists imported the first computers into the
      Netherlands from the USA, and started small businesses from 1975 onwards. They
      developed a social network in which computer technology was made available for
      use by individuals. This network extended itself via shops, clubs, magazines, and
      other means of acquiring and exchanging computer hard- and software. Hobbyist
      culture established the software-copying habits of private computer users as well
      as their ambivalence to commercial software. They also made the computer into a
      game machine. Under the impulse of a national policy that aimed at transforming
      society into an 'Information Society', clubs and other actors extended their
      activities and tailored them to this new agenda. Hobby clubs presented themselves
      as consumer organizations and transformed into intermediary actors that filled
      the gap between suppliers and a growing group of users. They worked hard to give
      meaning to (proper) use of computers. A second impulse to the increasing use of
      computers in the household came from so-called 'private-PC' projects in the late
      1980s. In these projects employers financially aided employees in purchasing
      their own private PCs'. The initially important intermediary actors such as hobby
      clubs lost control and the agenda for personal computers was shifted to
      interoperability with office equipment. IBM compatible PC's flooded the
      households. In the household the new equipment blended with the established uses,
      such as gaming. The copying habits together with the PC standard created a risky
      combination in which computer viruses could spread easily. New roles arose for
      intermediary actors in guiding and educating computer users. The activities of
      intermediaries had a lasting influence on contemporary computer use and user
      preferences. Technical choices and the nature of Dutch computer use in households
      can be explained by analyzing the historical developments of intermediaries and
      users.

PMID- 22586756
TI  - [Datanet 1 and the convergence of the computer and telecommunications].
AB  - This article describes the efforts of the Dutch national company for
      telecommunication, PTT, in introducing and developing a public network for data
      communication in the Netherlands in the last decades of the twentieth century. As
      early as the 1960s, private companies started to connect their local computers.
      As a result, small private computer networks started to emerge. As the state
      company offering general access to public services in telephony, the PTT strove
      to develop a public data network, accessible to every user and telephone
      subscriber. This ambition was realized with Datanet 1, the public data network
      which was officially opened in 1982. In the years that followed, Datanet became
      the dominant network for data transmission, despite competing efforts by private
      companies and computer manufacturers. The large-scale application of Datanet in
      public municipal administration serves as a case study for the development of
      data communication in practice, that shows that there was a gradual migration
      from X-25 to TCP/IP protocols. The article concludes by stating that the
      introduction and development of data transmission transformed the role of the PTT
      in Dutch society, brought new working practices, new services and new
      responsibilities, and resulted in a whole new phase in the history of the
      computer.

PMID- 22586757
TI  - [The South-American eel. Two early letters on animal electricity from the Dutch
      colonies].
AB  - Speculations about the nature of nerve action, including animal spirits, date
      back to antiquity. Only during the 18th century, when it became possible to store
      electricity in Leyden jars, did natural philosophers begin to realise that the
      sensations caused by electric fish are like those produced by these primitive
      capacitors. The important roles played by amateur observers in the Dutch colonies
      of South-America, and how they communicated with more established Dutch
      scientists in The Netherlands, are often relatively overlooked in histories of
      how the nerves became electrical. In this article we examine two mid-18th-century
      letters from South-America to the Netherlands. Both dealt with what would soon be
      called the electric eel, and were published in the proceedings of the first Dutch
      Society of Science (in Haarlem). The discovery of the electric nature of the
      shocks produced by these fish in particular proved to be a crucial step in
      understanding animal electricity and the true nature of neurophysiology.

PMID- 22586758
TI  - [The dangers of attendance. About the genesis of health care in Dutch schools (c.
      1900)].
AB  - In this article, the authors discuss the origins of the school medical service in
      The Netherlands. They focus on the period of transition from nineteenth-century
      concern for school hygiene--focusing on the improvement of buildings, school
      desks and timetables--to twentieth-century prevention of diseases and infirmities
      through medical inspection of pupils' health by school doctors. The research
      shows that in the Netherlands, when compared to Belgium and England, the state
      played only a minor role in this respect, as no legislation was introduced.
      Moreover, the instructions of the first generation of municipal school doctors
      were limited to medical examination; treatment of the illnesses they found
      continued to be the privilege of private practitioners. The sectarian character
      of Dutch society around 1900 seems to have been an important circumstance,
      stimulating restraint from interfering with religion-based education and its
      pupils in particular on the part of the government. School doctors' limited
      instruction appears to have been crucial for the acceptance of the service for
      denominational groups. Teachers' organisations welcomed the service, as they
      admitted their own lack of hygienic knowledge and the service did not interfere
      with teaching itself. Nevertheless, compulsory education seems to have ruled out
      other solutions to reduce the dangers of classroom education, particularly
      catching contagious and other 'school' diseases. The medical profession did not
      have to act as imperialists to become the protector of children that were forced
      to go to school. In the Netherlands, school medical inspection was created by a
      society that no longer accepted the health hazards of classroom education.

PMID- 22586759
TI  - [Yesterday, today, tomorrow. A retrospective look at the acid rain problem].
AB  - Last century, at the end of the seventies, Europe was startled by a serious
      environmental problem: acid rain. Acid rain was held responsible for the decline
      of fishes in Scandinavian lakes. Later, it was suggested that acid rain could
      lead to forest dieback over vast areas of Europe. Forests in the Netherlands
      could be at great risk, as well. It was clear to everyone what it was all about,
      for 'rain' means water falling from the atmosphere and the meaning of 'acid' was
      evident, too. Acid rain caused much commotion in the eighties but, since then, it
      has faded into the background. Why is it, that there is so little attention paid
      to acid rain these days? Maybe the acid rain problem was a hype; with an
      exaggerated reaction to a problem that was, in fact, insignificant. This article
      aims to reconstruct the history of one of the most prominent environmental
      problems of the twentieth century. The article describes the origin of the acid
      rain problem in the 1960s and describes the scientific research that was carried
      out to develop a better understanding of the problem from an atmospheric chemical
      point of view. Subsequently, it treats the rise of public awareness in the
      seventies. The article subsequently focuses on the situation in the Netherlands.
      The initial research into forest health showed alarming results. This led to
      widespread concern within The Netherlands, which, once more, urged the government
      to come into action. Some measures to reduce air-polluting emissions were already
      taken in the early 1980s. However, these were meant, mainly, to improve local air
      quality. As the eighties progressed, acid rain provided an additional argument
      for reducing air pollution. This article presents the consequences of the
      emission reductions for the acidity of acid rain, and it discusses--in brief--the
      acid rain problem in light of current scientific knowledge. Finally, it answers
      the question of why forests did not die.

PMID- 22586760
TI  - [Altruistic public servant or heroic genius? The propagated image of provincial
      and academic directors of bacteriological laboratories in Belgium (ca. 1900
      1940)].
AB  - At the end of the nineteenth century provincial bacteriological institutes were
      established in Belgium--in Liege, Mons, Namur and Brussels--in order to combat
      epidemics, to promote preventive medicine and to pursue the successful research
      of Louis Pasteur and Robert Koch. Similar laboratories existed at the
      universities of Ghent, Louvain and Brussels. The image building played an
      important role for both kinds of institutes, as bacteriology in pioneering phase
      had to be publicly confirmed as a new, valuable discipline. However, the
      directors of provincial and academic institutes--with the same academic training
      though--were awarded with different qualities at their jubilees, fitting with the
      purposes and the self-image of their respective institutions, either provincial
      authorities or universities. The image of academic directors was guided by
      academic decorum: Emile van Ermengem, Edmond Destree and Joseph Denys were
      represented as savants, solely devoted to pure science and paternally educating
      young researchers, notwithstanding the fact that their laboratories had
      humanitarian merits as well. On the other hand, the discourse on the first
      provincial directors--Ernest Malvoz, Martin Herman, Achille Haibe--emphasized
      their altruistic commitment and their solid work for the provincial government.
      Jules Bordet, a internationally rewarded scientist, professor and provincial
      director of the Pasteur Institute in Brussels, was celebrated with both sorts of
      discourses.

PMID- 22586761
TI  - ['Piracy of kowledge'--the role of a buccaneer-scientist in the knowledge
      circulation around diseases and drugs in the tropics].
AB  - Knowledge circulation in the seventeenth and eighteenth centuries was not only
      stimulated by the mutual interaction of trade and science. In the context of
      territorial expansion, war, and the activities of privateers and pirates,
      knowledge of diseases and drugs in the tropics was increased as well. An
      important part in this process was performed by so-called 'buccaneer-scientists':
      adventurers with medical and scientific backgrounds and/or interest who operated
      on the cultural borders in different parts of the hemisphere. The characteristics
      of this type of contributor to Early Modern knowledge circulation are explored
      and analyzed in the example of Scottish surgeon and pirate Lionel Wafer (c. 1660 
      c. 1705). The buccaneer scientist had to share the passions of other scientists,
      resulting in accurate and detailed empirical observation; be able to judge the
      relevance of observations and 'facts'; be part of a context that stimulates these
      observations; be capable of describing of these observations; and be part of a
      network of dissemination of observations. His activities should have an important
      practical and pragmatic component stimulating trade, expansion and even piracy.
      And he should possess personal characteristics such as perseverance, a healthy
      constitution, and ruthlessness, to work and survive in a violent and traumatic
      environment. Wafer is typical for other 'buccaneer-scientists' of this period-
      not only pirates and privateers, but also physicians and natural explorers
      operating in other and more 'respectable' areas of the European overseas
      expansion.

PMID- 22586763
TI  - [From 'triumphalism' to 'postcolonialism': trends in the historiography of
      tropical medicine].
AB  - This article highlights some of the most remarkable trends in the historiography
      of tropical medicine. Focusing on the literature that deals with the 19th and
      20th centuries, it describes how by the 1980's triumphalist, apologetic histories
      were replaced by critical studies that revealed the less positive sides of
      tropical medicine. It also talks about the increasing influence in medical
      historiography of the postcolonial body of thought and its dynamic perspective on
      colonial categories and relations. This postcolonialism turns out to be a
      fruitful approach, as is shown especially by recent studies that focus on the
      production of tropical medical knowledge. In fact, the historiography of tropical
      medicine increasingly contributes to the growing body of literature on science
      and imperialism that looks for postcolonial alternatives to the diffusionist
      paradigm. This concern to reject diffusionism (which views imperialism as the
      basis for the spread of European science to the non-western world) has been
      noticeable particularly in the Anglo-Saxon academic world. This article calls for
      the adoption of similar approaches in other historiographic traditions.

PMID- 22586762
TI  - [Coping with leprosy in the Dutch West Indies in the 19th century; opposing but
      meaningful views from Suriname].
AB  - Leprosy was highly prevalent among African slaves in the Dutch West Indian colony
      of Suriname. Largely based on observations in Suriname, Dutch physicians
      described the aetiology of leprosy in terms of'a substrate' to which all sorts of
      mixtures of infection, heredity and hygiene contributed ('seed and soil'). This
      explanatory model with multiple options for prevention and treatment left room
      for different developmental trajectories to control the spread of the disease in
      the various tropical colonies of the Dutch empire. In Suriname there was a
      growing worry in the 19th century regarding the spread of leprosy, threatening
      the health of slaves, settlers and colonial administrators. And this could be
      harmful to an already weakening plantation economy. This concern prompted the
      local administration to develop a rigorous policy of strict isolation of leprosy
      sufferers. This, in turn, intersected with a changing insight in Europe -
      including the Netherlands - that leprosy was non-contagious. However,'in splendid
      isolation' in the economically and politically marginal colony Suriname, Dutch
      physicians like Charles Landre and his son, Charles Louis Drognat Landre, could
      afford to ignore the European non-contagious approach and continue to support the
      strict isolation policies. Moreover, they developed a dissident radical
      explanation of leprosy as a disease caused only by contagion. In the absence of a
      receptive Dutch audience Drognat Landre published his contagion theory in French
      and so succeeded in inspiring the Norwegian Hansen, who subsequently discovered
      the culpable micro-organism. At the same time colonial administrators and
      physicians in the economically and politically important Dutch colonies in the
      East Indies adhered to the prevailing European concept and changed policies: the
      system of isolation was abolished. Given the rather different trajectories of
      leprosy health policies in the Dutch East and West Indies we point out the
      importance of a comparative approach.

PMID- 22586764
TI  - [The foundation of the Dutch Society for Tropical Medicine: an affair of national
      importance].
AB  - The 'Nederlandsche Vereeniging voor Tropische Geneeskunde' (Dutch Society for
      Tropical Medicine--in short: NVTG) was founded in 1907, a time not only of
      colonial expansion, but also a time in which the economic interest of the Dutch
      East-Indies for The Netherlands grew exceptionally. This had its effect on the
      motivations behind medical aid. Hygienic measures were financially backed because
      healthy workers had a positive effect on profits. This atmosphere of economic
      interest and political-military expansion had its effect on the foundation of the
      NVTG as well. Colonialism was generally approved of, and the goal of the society
      apart from sociability motives--was to support research into illnesses torturing
      mainly the Dutch colonies. This was in line with the reasoning that the colonies
      were rightfully governed by the Netherlands, because the peoples living there had
      proven not to be able to look after themselves in a proper manner. The foundation
      of the Society should have been a part of the foundation of an international
      society for tropical medicine, but this failed. Although internationalism
      generally was seen as an important feature of science and certainly of medical
      science, it is not strange this was not seen as a major problem. For it was
      national and not international reasons that had led to founding the Dutch
      society. It was the Dutch position as a colonial power that had convinced Dutch
      tropical doctors a society should be called into being. A generally shared spirit
      of internationalism had little to do with this unless internationalism is defined
      as: what others have, we need to have as well, and let us see in international
      conferences what could be of national benefit. That nevertheless this spirit of
      internationalism--and not nationalism--is commonly hailed as the main reason
      behind the foundation, is probably due to the fact that around 1900 nationalism
      was such a normal state of mind and so fully incorporated in man's way of
      thinking and acting, that, as for instance was the case with racism, it was hardy
      noticed and recognised as such.

PMID- 22586765
TI  - [Medical policies, state and religious missions in Rwanda (1920-1940). An
      authoritative design of colonial medicine?].
AB  - The Belgian health policy set up in mandated Rwanda after the First World War was
      mainly centred on some campaigns taking specifically yaws as a target. The
      struggle against this endemic disease (not fatal, but most disabling) was
      organized in a very systematic and authoritarian way. This article looks into two
      of those yaws campaigns, questions their runnings and alterations, and finally
      brings to light the intra-colonial tensions between the health services and the
      administration on the one hand, between the colonizers and the African
      populations on the other hand.

PMID- 22586766
TI  - [The Prince Leopold Institute for Tropical Medicine in Antwerp: an overview].
AB  - The struggle against the sleeping sickness in Congo was the major reason for the
      opening of a School of Tropical Medicine (1906). The edition of new statutes in
      1931 at the moment of the transfer to Antwerp conformed the autonomous and
      neutral character of the Institute. On the other hand, as the person responsible
      to the community represented by the Ministery of Colonies and--later--the
      Ministery of Education, she had to publish an annual report on their activities
      and finances.After the independence of the colony (1960) the teaching and
      research policy accentuated development aid, and in particular the fight against
      tropical disease (malaria, sleeping sickness, leishmaniasis...) and HIV (AIDS and
      Tuberculosis). The Institute delivers postgraduate and master's degrees. Each
      year, two hundred doctors and nurses attend its classes, and around a hundred
      students from over the world prepare for their medical degree. The Institute of
      Tropical Medicine in Antwerp is a'center of excellence' and an important
      component in an international network that aims for 'Health for all'.

PMID- 22586767
TI  - [Cohen comment].

PMID- 22586768
TI  - [About real and fictional people in 'How Modern Science Came into the World' by
      Floris Cohen: Ibn al-Haytham, al-Toesi, al-Kepler and al-Galilei].

PMID- 22586769
TI  - [About essential questions, necessary and satisfactory conditions].

PMID- 22586770
TI  - [The Socratic problem and the challenge of Newton. How to understand 'How Modern
      Science Came into the World' better].

PMID- 22586771
TI  - [The end of all world images? Modern natural science and religion].

PMID- 22586772
TI  - [The war metaphor. About the relationship between religion and science].

PMID- 22586773
TI  - [Answers to my critics].

PMID- 22586776
TI  - [Peter Debye and the Commission-Terlouw. Reaction to the discussion about Debye
      in the previous issue of Studium].

PMID- 22586775
TI  - [The development of Rein van Bemmelens (1904-1983) undation theory: forty years
      of Dutch geology].
AB  - The Dutch geologist Rein van Bemmelen was the greatest opponent of plate
      tectonics in The Netherlands. He lived and worked during an important period in
      the history of earth sciences. He had studied geology when Wegeners theory was
      introduced and enthusiastically received in the Netherlands and he worked as a
      geologists during the period in which, after Wegeners theory was rejected in The
      Netherlands, several Dutch geologists came with their own theories to explain the
      origin of continents and oceans and in which plate tectonics was introduced in
      The Netherlands. He had proposed his own theory, the undation theory, at the
      beginning of the 1930s and kept on developing it during the following years. He
      continued to do so until his death in 1983. The history of the undation theory
      thus sheds light on the history of geology in The Netherlands. I will trace the
      history of geology in The Netherlands using Rein van Bemmelen and his undation
      theory as a lens.

PMID- 22586774
TI  - Journals under threat. A joint response from History of Science, Technology and
      Medicine editors.

PMID- 22586777
TI  - [An analytical visualization practice. The pathological-anatomical illustrations
      of Jean Cruveilhier in relation to clinical observations].
AB  - The article examines the meaning and function of medical illustrations in the
      famous Atlas Anatomie pathologique, published by the French surgeon Jean
      Cruveilhier (1791-1874). By tracing the complex representation of pathological
      entities both back to the visual tradition of anatomy and the semiotic tradition
      of case descriptions and case histories, the article identifies the visualization
      technique of Cruveilhier as an analytical practice. The illustration of
      pathological anatomy gains a functional diagnostic quality when bound to case
      descriptions and clinical histories. The Atlas serves thereby as a sample to
      trace the genealogies of a clinical visualization practice in characteristic
      images that is both engaged with an individual case and classificational tasks.

PMID- 22586778
TI  - [Max Planck--an adversary of Christianity? The debate about Planck's attitude
      towards religion after World War II].
AB  - The article discusses a debate which unfolded in the early 1950s and 1960s
      between East German Marxist philosophers and historians of science and West
      German theologians and scientists. The subject treated was the attitude towards
      religion of famous physicist Max Planck who had died a few years earlier, in
      1947. The article analyses the different positions of the contributors, mainly
      with a view to developing a categorial framework usable in descriptions and
      analyses of the religious attitudes of natural scientists. Moreover the different
      stages of the debate are outlined in order to exhibit their connections to the
      larger historical context, i.e. the unfolding of the cold war. In the light of
      this the debate can be regarded as a religious or ideological war, albeit a cold
      one, on German soil, which fortunately did not escalate into a hot conflict. It
      ended, as can be illustrated in a late contribution to the debate, with the
      collapse of the GDR in 1989 or shortly thereafter.

PMID- 22586779
TI  - Rocket scientists need not apply.

PMID- 22586780
TI  - Avoiding emergency stops in end of life care.

PMID- 22586781
TI  - Improving end-of-life care: recommendations on professional development for
      physicians.

PMID- 22586782
TI  - Dysfunctional doctors--will revalidation help?
AB  - Numbers of National Clinical Assessment Service referrals concerning
      practitioners' performance are much higher for the over-50s, especially in GPs.
      In 20% of cases there are concerns with diagnosis that are unlikely to be
      recognised by revalidation. Accurate and timely diagnosis is fundamental to
      patient safety, and the results of studies in which GPs were tested using mystery
      patients are not encouraging. We need to assess pratictioners' competencies in
      diagnosis throughout their careers. Plans to extend working life may require
      changes to the clinical responsibilities of older doctors.

PMID- 22586783
TI  - Service provision for liver disease in the UK: a national questionnaire-based
      survey.
AB  - The National Plan for Liver Services in 2009 called for a review of current liver
      services across the UK to identify areas of good and poor provision. We present
      the results of a national questionnaire survey of liver services, which focussed
      on staffing and training, access to key facilities and clinical management of
      liver disease. Areas of good practice include the increased proportion of
      consultants who trained at a liver centre, the introduction of specific liver
      clinics and the widespread use of terlipressin and antibiotics for variceal
      bleeding. Areas of poor practice include limited access to alcohol psychiatry
      services and transjugular intrahepatic portosystemic shunts (TIPS) and limited
      recording of outcome measures or patient databases. Wide variation in the
      clinical management of serious liver diseases supports the need for managed
      clinical networks. These results will help to guide the development of standards
      of care for liver services across the UK.

PMID- 22586784
TI  - Simple prescribing errors and allergy documentation in medical hospital
      admissions in Australia and New Zealand.
AB  - This study aimed to quantify and compare the prevalence of simple prescribing
      errors made by clinicians in the first 24 hours of a general medical patient's
      hospital admission. Four public or private acute care hospitals across Australia
      and New Zealand each audited 200 patients' drug charts. Patient demographics,
      pharmacist review and pre-defined prescribing errors were recorded. At least one
      simple error was present on the medication charts of 672/715 patients, with a
      linear relationship between the number of medications prescribed and the number
      of errors (r = 0.571, p < 0.001). The four sites differed significantly in the
      prevalence of different types of simple prescribing errors. Pharmacists were more
      likely to review patients aged > or = 75 years (39.9% vs 26.0%; p < 0.001) and
      those with more than 10 drug prescriptions (39.4% vs 25.7%; p < 0.001). Patients
      reviewed by a pharmacist were less likely to have inadequate documentation of
      allergies (13.5% vs 29.4%, p < 0.001). Simple prescribing errors are common,
      although their nature differs from site to site. Clinical pharmacists target
      patients with the most complex health situations, and their involvement leads to
      improved documentation.

PMID- 22586785
TI  - Living for the weekend: electronic documentation improves patient handover.
AB  - With increasing shift work the importance of effective handover is becoming more
      widely recognised, resulting in the production of guidelines on written handover
      documentation. A particular area of poor compliance was handover from the week to
      weekend teams for medical inpatients, as shown through an audit cycle. Full
      implementation of any guidelines can be time and financially costly. However, a
      simple, minimal cost, electronic-based list improved the quantitative measures of
      written handover, particularly in areas of patient location, resuscitation status
      and investigations. Qualitative data showed multiple benefits, but also problems
      with logistics in computer terminals, networks and access. Solutions to such
      problems are discussed, with the importance of carefully implemented longer-term
      changes being emphasised.

PMID- 22586786
TI  - Opening the oyster: the 2010-11 NHS reforms in England.
AB  - This opinion paper briefly considers the credibility of the announced rationale
      behind the current extensive reform of the NHS in light of recent research
      evidence about performance of the system. The paper outlines the authors' views
      of the history of the reform, which originates in a set of documents, produced in
      the late 1980s by the Centre for Policy Studies, which aimed to introduce private
      sector involvement throughout the NHS, and a brief report by a consultant for a
      health maintenance organisation in the USA. Tracking of the pro-private sector
      changes in the NHS demonstrates that the bill is a major step in the
      implementation of NHS privatisation and also delineates a roadmap for coming
      developments, which have been explained to corporate providers and investors
      seeking new profit opportunities but have not yet been debated openly with the
      electorate in the UK.

PMID- 22586787
TI  - Intravenous diuretic day-care treatment for patients with heart failure.
AB  - Fluid overload is a common manifestation of decompensated chronic heart failure.
      This paper reports on a pilot study that investigated whether intravenous (i.v.)
      furosemide administered on a cardiology day ward for three successive days was
      effective in improving the symptoms of patients with fluid overload and chronic
      heart failure. The results showed that 94.1% of patients reported an improvement
      in their breathlessness, with a marked weight loss in 88.2% of patients. There
      were no marked changes in blood pressure or renal function. Hospital admission
      was avoided in 94.1% of cases. The study concluded that i.v. diuretic treatment
      given in a hospital day-care setting is safe and effective, and that it reduces
      the need for hospital admissions. As a consequence, this reduces the associated
      financial costs of hospitalisation.

PMID- 22586788
TI  - Assessing the relationship between admission glucose levels, subsequent length of
      hospital stay, readmission and mortality.
AB  - This study aimed to investigate relationships between dysglycaemia and length of
      hospital stay, short-term mortality and readmission in an unselected population
      in an acute medical unit (AMU). The rate of follow up in non-diabetic individuals
      with hyperglycaemia was also measured. We analysed data from all 1,502 patients
      admitted through our AMU in February 2010 to assess blood glucose levels on
      admission, length of stay, 28-day readmissions and mortality, and to determine
      whether blood glucose > or = 11.1 mmol/l on admission in non-diabetic individuals
      was followed up. In total, blood glucose was measured on admission for 893
      patients. Mean length of stay was 8.8 (standard deviation 11.9) days, for
      patients with blood glucose < 6.5 mmol/l on admission; 11.3 (13.6) days, for 6.5
      7 mmol/l; 10.2 (14.5) days, for 7.1-9 mmol/l; 10.6 (14.9) days, for 9.1-11
      mmol/l; 12 (18.4) days, for 11.1-20 mmol/l and 9.1 (11.2) days, for > 20.1
      mmol/l. Length of stay for patients with blood glucose > 6.5 mmol/l on admission
      was significantly longer (p = 0.002). The 28-day readmission rates were 6.4%, 6%,
      9.7%, 12.5%, 10% and 15%, respectively, and 28-day death rates were 4.8%, 6%,
      5.8%, 17.2%, 17.1% and 6.1%, respectively. Overall, 51.4% of non-diabetic
      individuals with blood glucose > 11.1 mmol/l on admission were followed up. The
      study showed that blood glucose > 6.5 mmol/l on admission is associated with
      significantly longer length of stay. Hyperglycaemia was associated with increased
      28-day mortality and readmissions, and is frequently underinvestigated.

PMID- 22586789
TI  - Preclinic telephone consultations: an observational cohort study.
AB  - Patients referred to secondary care for specialist respiratory review frequently
      undergo multiple hospital attendances for investigations and consultations. This
      study evaluated the potential of a preclinic telephone consultation and
      subsequent coordination of tests and face-to-face consultations to reduce
      hospital visits. Total hospital attendances were recorded for three cohorts
      (participants, non-participants and comparators) for 6 months from first
      specialist contact. Patients completed the medical interview satisfaction scale
      21 (MISS-21). The study showed that a preclinic telephone consultation can
      significantly reduce hospital visits over a fixed period without reducing patient
      satisfaction. In total, 20.8% of the participant group had three or more hospital
      attendances compared with 42.9% of the non-participant group (p = 0.001) and
      44.7% of the comparator group (p = 0.002). Participants had fewer follow up
      visits and lower rates of non-attendance/late rearrangement of appointments. This
      service reduces unnecessary hospital visits, seems to improve patient compliance
      and may save costs associated with non-attendance and follow up consultations.

PMID- 22586790
TI  - Revalidating Sherlock Holmes for a role in medical education.
AB  - Sir Arthur Conan Doyle endowed Sherlock Holmes with extraordinary skills that Dr
      Watson and others found incomprehensible until Holmes gave explanations, often in
      the form of memorable maxims and short monologues. Intentionally or not, Doyle
      left us crime-solving precepts that still inform aspects of medical practice.
      Experienced clinicians share with Holmes the dilemma of how to make complex,
      often unconscious, capability accessible to novices. Doctors still invoke
      Holmes's methods in clinical contexts, but the validity of some of the parallels
      has been challenged and quoting the more popular sayings has been equated with
      conceit. This paper examines how the use of selected maxims and monologues can
      help to link abstract principles and live context in a credible way in order to
      make aspects of clinical reasoning and professional behaviour more accessible and
      memorable.

PMID- 22586791
TI  - An unusual cause of bleeding in an elderly patient.

PMID- 22586792
TI  - Osteoarthritis: a holistic approach.
AB  - Osteoarthritis represents a massive and rapidly increasing burden on our society
      and the NHS. Current treatments are limited in efficacy and have significant
      toxicities. A conference was organised in conjunction with the British Society of
      Rheumatology with the aim of updating frontline clinicians and researchers on the
      size and causes of this problem, with a focus on modern management.

PMID- 22586793
TI  - Concise guidance: diagnosis, management and prevention of occupational asthma.
AB  - This concise guidance, prepared for physicians, summarises the British
      Occupational Health Research Foundation guideline for the prevention,
      identification and management of occupational asthma. Approximately one in six
      people of working age who develop asthma have work-related asthma, where work has
      either caused or aggravated their disease. Physicians who assess working adults
      with asthma need to ask the patient about their job and the materials they work
      with, and be aware of those that carry particular risks; they should also ask
      whether symptoms improve regularly on days away from work. A diagnosis of
      occupational asthma (ie asthma caused by work) should not be made on the basis of
      history alone, but be supported by immunological and physiological investigations
      of proven diagnostic benefit. Following a validated diagnosis of occupational
      asthma, physicians should recommend early avoidance of further exposure, because
      this offers the best chance of complete recovery. If appropriate and timely
      interventions are not taken, the prognosis of occupational asthma is poor, with
      only approximately one-third of workers achieving full symptomatic recovery.

PMID- 22586794
TI  - Management of cutaneous T-cell lymphoma.

PMID- 22586795
TI  - The urticarias: pathophysiology and management.

PMID- 22586796
TI  - Advances in the treatment of melanoma.

PMID- 22586797
TI  - Systemic treatment of adult atopic dermatitis.

PMID- 22586798
TI  - Vasculitic rash: do not jump to conclusions.

PMID- 22586799
TI  - Treating acute asthma--salbutamol may not always be the right answer.

PMID- 22586800
TI  - Vetting requests for molecular diagnostics for CNS infections based on
      cerebrospinal fluid measurements undermines the quality of patient care.

PMID- 22586801
TI  - Lessons of the month.

PMID- 22586802
TI  - Let's hear it for the medical registrar.

PMID- 22586803
TI  - The impact of twice-daily consultant ward rounds on the length of stay in two
      general medical wards--effect on training?

PMID- 22586804
TI  - Offering HIV testing in an acute medical admissions unit in Newcastle upon Tyne.

PMID- 22586805
TI  - Acute hypercapnic respiratory failure (AHRF): looking at long-term mortality,
      prescription of long-term oxygen therapy and chronic non-invasive ventilation
      (NIV).

PMID- 22586806
TI  - European School of Internal Medicine summer meeting: September 2011.

PMID- 22586807
TI  - Clinical coding for electrophysiology and device procedures: why and how to get
      it right.

PMID- 22586808
TI  - Closing the therapeutic gap in patients with low vitamin B12 levels.

PMID- 22586809
TI  - [Psychiatry in multiplicity].
AB  - According to a widespread interpretation, the history of psychiatry is
      characterized by a strong opposition between biological and psychological
      paradigms, which would dominate consecutive periods in history. The image of a
      swinging pendulum is a popular metaphor to describe this idea. The culture of
      Dutch psychiatry in the interwar years (1918-1940) seems to gainsay this image.
      Psychological, biological and socials models of explanation and therapy were used
      alongside each other without apparent debate and conflict. Influential professors
      of psychiatry like H.C. Rumke (Utrecht University) even pleaded for a conscious
      integration of these approaches. Some historians have interpreted this stance as
      a sign of scientific 'vagueness' and 'anarchy'. Analyzing the work of three major
      representatives of Dutch psychiatry in the Interbellum (Leendert Bouman, Han
      Rumke and Lammert van der Horst), the authors (former students of the master
      Historical and Comparative Studies of the Sciences and the Humanities) shed light
      on the psychiatric climate of this era, dealing with themes like the openness of
      psychiatry to other sciences, the interactions of psychiatry and literature, and
      the relationship between theory and clinical practice. As a result a further
      qualification of the image of the pendulum is argued for.

PMID- 22586810
TI  - [The pendulum, the gap, and the clinic. Leendert Bouman (1869-1936) and the
      'psychological turn' in Dutch psychiatry].
AB  - In recent historical literature, the Dutch psychiatrist Leendert Bouman (1869
      1936) is named 'the godfather of psychological psychiatry'. He is regarded as one
      of the exponents of a shift or 'pendulum' movement from a biological
      materialistic to a psychological, phenomenological orientation in the Dutch
      psychiatry of the Interbellum. As a professor of the orthodox calvinist Vrije
      Universiteit of Amsterdam, he explicitly opposed a 'soul-less', biological
      reductionist psychiatry. In addition, he played an important part in the
      introduction and spread of new'psychological' theories and especially Karl
      Jaspers' phenomenology in The Netherlands. It is one-sided and misleading,
      however, to refer to Bouman as a 'psychological' psychiatrist. Most of his
      scientific work was of a neurological and biological nature. He did not see
      biological (or nomothetic) and psychological (or idiographic) approaches as
      mutually exclusive, but as necessarily complementary. In this he followed
      Jaspers' distinction between and complementary use of the causal connections of
      psychic life (explanatory psychology) and meaningful psychic connections
      (psychology of meaning). Boumans pluralist orientation was rooted in his
      fundamentally clinical attitude toward psychiatry. In his view, a psychiatrist
      was in the first place a clinician. In the clinic, he stressed, a psychiatrist
      has to view and examine each individual patient in his bio-psycho-social
      totality. The case of Bouman illustrates that the history of psychiatry is by far
      richer and more complicated than is suggested by the standard account of that
      history being characterized by a pendulum movement and a one-dimensional struggle
      between 'somatic' and 'psychological' schools. It also suggests that the
      interaction between theory and clinical practice should be emphasized as an
      important dynamic factor in the history of psychiatry--next to or even above the
      dichotomy between 'biology' and 'psychology'.

PMID- 22586811
TI  - [As a clincian beyond the boundaries of psychiatry. The congeniality of
      literature and psychiatry in the work of psychiatrist H.C. Rumke (1893-1967)].
AB  - One of the most important Dutch psychiatrists in the interwar period was H.C.
      Rumke (1893-1967). With his eclectic interest in psychiatric approaches such as
      both psychoanalysis and phenomenology, Rumke is most well known for his
      remarkable diagnostic and therapeutic skills. The life and work of Rumke has been
      studied in detail, most notably by the Dutch historian Jacob Van Belzen. Despite
      this extensive research, in this paper it is stated that a relevant aspect of
      Rumke's work has been largely disregarded--namely his profound interest in and
      use of poetry and literature. Not only did Rumke write poems himself under the
      pseudonym of H. Cornelius, in his scholarly work he frequently refers to
      fictional literature and at the end of his career he wrote a comprehensive
      analysis of Frederik van Eeden's novel Van de Koele Meeren des Doods. For the
      eclectic clinician Rumke literature and poetry are a source of knowledge to gain
      insight into the human psyche. Furthermore, according to Rumke, often literature
      succeeds better at expressing the human condition than the science of psychiatry
      can. In this article it is argued that for a coherent interpretation of the life
      and work of Rumke this literal and poetic aspect of his work cannot be
      disregarded. It is precisely Rumke's profound interest in literature and poetry
      that reflects his two main theses about the science of psychiatry. These are on
      the one hand the centrality of clinical practice and on the other hand the
      boundaries of psychiatry. As a clinical practitioner Rumke's aim was to be able
      to understand the suffering of the patient - literature and poetry could help him
      do that. Rumke's use of literature and poetry can be understood by taking into
      account the context of the clinic, but the intertwinement between psychiatry,
      literature and poetry in Rumke's work also reflects a broader issue. Namely that
      the science of psychiatry is not omnipotent and that sometimes the arts are
      better equipped to grasp the human condition.

PMID- 22586812
TI  - [The totality of man. The anthropological approach to psychiatry in the work of
      Lammert van der Horst (1893-1978)].
AB  - The anthropological approach was one of the new approaches to psychiatry that
      emerged in the interbellum. In The Netherlands professor Van der Horst (VU
      university Amsterdam and the municipal University of Amsterdam) was its most
      prominent proponent. The general idea of the anthropological approach was to
      integrate the various ways of knowing then available. A psychiatric disease was
      seen as the result of a failure in the self-realisation of the individual person.
      This required to consider all relevant aspects relating to the patient's
      existence. How to tailor these ideas to concrete forms of diagnosis and methods
      of treatment was no easy matter and Van der Horst devoted himself all his life to
      this task. He first sought to classify man in three or four types of character
      inspired by the works of Heymans and Kretschmer. Then he tried to give the
      specific human aspect its place in psychiatry by introducing a 'pneumatic'
      dimension in his analysis of persons. He also connected this dimension to
      Calvinism, the church he belonged to. In the 1940's he made a turn towards
      existentialism and tried to connect this philosophy to anthropological
      psychiatry. In spite of its fragmentary appearance I believe it is possible to
      discern a degree of continuity in the work of Van der Horst. The concern with the
      specifically human was always central to him. Moreover Van der Horst saw no
      strict divide between addressing questions in psychiatry and thinking about the
      greater questions of life which provides an explanation for his meandering
      thoughts. The dissertation of J.H. van den Berg which appeared in 1946 offers an
      interesting contrast to Van der Horst. To Van den Berg the anthropological
      approach was no more than a method best developed by Binswanger. Van den Berg
      tested this method and concluded that the approach could offer hermeneutic
      insights at points where methods of the natural sciences fell short. These
      restrictions had the sake of clarity. In stark contrast, and in spite of all his
      efforts, many aspects in the work of Van der Horst remained obscure. However his
      search for an overarching anthropological approach to psychiatry is still
      interesting to us because it questions what the borders of the field actually
      are. Since the various approaches to psychiatry are still at best loosely
      integrated this question is of continuing relevance.

PMID- 22586813
TI  - [From relativism to evaluation. Recent trends in the historiography of science
      and the humanities].
AB  - Historians of science have taken leave of finalism. No longer do they write
      teleological histories of scientific progress. Instead of a grand narrative on
      the triumph of science they now tend to write small stories on local knowledge.
      This is the result of several decades of criticism of Whig history. Starting with
      neo-marxist critique in the interwar years, enhanced in the social history of the
      1970s, science was seen as an economic commodity and as a social product.
      Cultural history and anthropology added the view that scientists and scholars are
      mere mortals, muddling through messy life. This critique was topped off with
      postmodern criticism of knowledge as power, which translates into the accusation
      that historiography is only legitimating cultural and political oppression. To
      counter these allegations, many historians have insulated themselves into a kind
      of retro-historicism that shies away from any teleology, coherence, meaning and
      evaluation. It depicts the production of knowledge as a practical, local activity
      that is strictly limited to its cultural context. No claims to truth, validity,
      let alone progress or even development were allowed. This situation of rampant
      relativism could not last. Total abstinence of any evaluation of knowledge
      claims, quality of research or success of theories has proven unsatisfactory. The
      need has arisen to study broader issues of traveling knowledge and longer lines
      of scientific development. There is a shift of interest into traditions of
      knowledge that spring the bonds of locality and context. Why do some scientific
      theories and research practices succeed in surpassing paradigms and bridging
      epistemic ruptures? In this respect disciplines are in the process of being
      rehabilitated. Instead of oppressive structures they become the vehicles of
      sustained knowledge growth. Especially the role of education and academic
      training is focused on. Facing up to the charges of conceptual anachronism,
      historians of knowledge now opt for a cautiously evaluative history. The
      alternative would be an intellectually barren historicism.

PMID- 22586814
TI  - [Long-term history of science: on the flexibility and fragility of scientific
      disciplines].
AB  - Most scientific disciplines, such as chemistry, biology and physics, are now
      about two centuries old. Using physics as a case study the present paper aims to
      account for this longevity. What kept the physics discipline together from the
      early nineteenth century onwards? Literature on the rise of physics suggests that
      the discipline was formed around energy, the ether, or other theoretical notions.
      Yet the twentieth-century revolutions in physics showed that the discipline could
      prosper without some of its most 'fundamental' concepts. Some scholars conclude
      that internal factors are therefore irrelevant and disciplinary identity and
      continuity are purely institutional. Drawing on the work of Thomas Kuhn, Peter
      Galison and Andrew Warwick, this paper defends a different point of view.
      Although there is no intellectual core of disciplines, the prolonged existence of
      disciplines cannot be explained without some degree of internal continuity. If
      there is a revolution of a theoretical level, there may still be continuity on
      the level of experimental practices (and vice versa). It is this flexibility that
      accounts for the fact that disciplines may adapt to different circumstances. In
      addition, an educational tradition is required to transmit knowledge from one
      generation to the next.

PMID- 22586815
TI  - [The 'national philologies' and the history of discipline formation in the
      humanities].
AB  - The start of discipline formation in the 'national philologies' (such as 'English
      language and literature', 'Germanistik', etc.) is often considered to have taken
      place around the middle of the nineteenth century. At that time, the German
      philological school of scholars such as Jacob Grimm gained influence at
      universities all over Europe. Meticulous analysis of the oldest (medieval) texts,
      as well as rigorous application of the methods of historical-comparative
      linguistics in editing these texts, became the norm and the nec plus ultra of
      philology. Other forms of academic and scholarly attention to national literature
      -e.g., the study of the history of literature in post-medieval and modern times-
      were from then on looked down upon as mere hobbies, made obsolete by the
      'modern', 'truly scientific' methods of the German school. The case of the
      'national philologies' thus seems to corroborate the common idea that discipline
      formation in science consists mainly of a process of specialization and
      differentiation. However, an overview of the history of 'Neerlandistiek' (the
      academic study of Dutch language and literature) over the course of the
      nineteenth century suggests that the success of German School's methods was in
      fact but a temporary episode. In the history of 'national philologies' such as
      the 'Neerlandistiek', episodes of specialization seem to alternate with episodes
      in which the main emphasis is not on specialization but on extension of the
      scope, on integration of elements from other disciplines, and on reinforcement of
      the ties with social institutions such as the education system.
      Interdisciplinarity is not a new phenomenon but can already be found in the days
      of the discipline's origin in Holland. Back then, the first professors of 'Dutch
      rhetorics' around 1800 rapidly expanded their specialist studies into the study
      of 'Dutch language and literature' in the broadest possible sense. Phenomena such
      as these seem to apply more generally to the process of discipline formation in
      the humanities. The fact that disciplines such as the 'national philologies'
      still exist, suggests that specialization, differentiation and 'boundary wars'
      are not the only road to scientific legitimacy. Extension of the scope,
      (re)unification with other disciplines and intense communication with social
      systems inside and outside university are at least as important.

PMID- 22586816
TI  - [The medical literature of the Egyptian campaign].
AB  - Bonaparte's Egyptian Campaign (1798 - 1801), like all other episodes from the
      Napoleonic era, gave rise to an extensive literature on the subject, but most of
      all a significant medical literature. This fact is due to many reasons:--an
      important health service for this expeditionary corps of more than 36.000 men,
      with two main figures at its hea, Desgenettes and Larrey--but also with valuable
      subordinates like Assalini, Savaresi, Balme, Pugnet or Barbes.--A Commission for
      Science and Art, of which a few doctors and surgeons were members, but most of
      all pharmacists like Boudet or Rouyer--The presence in the field of Ludwig Frank,
      the nephew of the famous Johann Peter Frank.--The creation in Cairo of an
      Egyptian Institute and the publication of the masterly Description of Egypt and
      the establishment of printing houses.--The emergence of the myth of the Orient
      and its mysteries.--An extensive array of indigenous pathologies, which is
      characteristic of those countries. For instance: plague, dysentery, yellow fever,
      Egyptian ophthalmia, as well as more common diseases like tetanus, scurvy or
      venereal diseases. The main medical works that cover this period and its
      pathologies are skimmed.

PMID- 22586817
TI  - [The humanitarian work of France in the Sahara. The Health Service of the army in
      the territories of Southern Algeria (1900-1976].
AB  - Medical assistance to the Saharian populations (1900-1976) is viewed through its
      organization. The management of the Health Service in the Southern Territories,
      doctors, nursing staff, medical districts, centred on infirmary-hospitals and
      rural first-aid posts. We insist on the everrising free consultations and the
      care to sick and wounded patients in infirmaries; the fight against epidemics and
      social scourges. Then on French medical mission from 1963 to 1976, and on the
      humanitarian work by the Health Service throughout the five continents.

PMID- 22586818
TI  - [Esquirol and dementia].
AB  - Jean Etienne Dominique Esquirol (1772-1840), after Pinel (1745-1826), stated
      precisely the symptoms of dementia according to the new medical definition of the
      word: a disease including all the states of intellectual weakness for various
      reasons. For example Esquirol clearly distinguished dementia from mania--that is
      to say our present psychoses--, and also from mental deficiency. In the same time
      Esquirol became more and more conscious, from 1814 (cf. his contributions to the
      Dictionnaire des sciences medicales, in 58 volumes, dir. Panckoucke) and 1838
      (his famous work Des maladies mentales), of the very nature of senile insanity
      compared with other kinds of dementia.

PMID- 22586819
TI  - [The doctor and the consul. Relations between Galen and Flavius Boethos under
      Marcus Aurelius].
AB  - The author describes the rich relationship between young Galen, just arrived in
      Rome from his native Minor Asia, and Flavius Boethos a consul suffectus who was
      to become the governor of Syria, and asked him to cure his wife and then their
      son, Cyrillos. Although very famous, Galen who never became a Roman citizen,
      needed such a friend and social mentor.

PMID- 22586820
TI  - [Wouter van Doeveren (1730-1783) professor of practical medicine, obstetrics and
      pathology].
AB  - Between September 1752 and July 1753, Wouter van Doeveren, a student of Gaubius,
      Albinus and Winter at Leyden University, studied, together with a couple of
      friends at various Paris hospitals in order to improve his skills in the fields
      of surgery and obstetrics. After his return to Leyden, he took his doctor's
      degree in medicine and started his practice in that town. In 1754 he was
      appointed professor of medicine at Groningen University. In 1770 he was appointed
      professor of theoretical and practical medicine at Leyden University. He held
      that office until his death on 31 December 1783. He was a most appreciated
      foreign member of the Societe Royale de Medecine (Paris) and of the Royal Society
      of Medicine (Edinburgh). He succeeded in improving his medical skills, by doing
      thorough research in the fields of pathological anatomy and teratology. He laid
      the foundations for national healthcare regulations for the United Provinces.

PMID- 22586821
TI  - [Drug advertising as communication between the pharmaceutical industry and the
      physician: advertisements for psychotropic drugs in the Dutch medical journal,
      Nederlands Tijdschrift voor Geneeskunde, 1900-1940].
AB  - In this article we explore the historical development of drug advertisements for
      psychotropic drugs in the leading Dutch medical journal from 1900 to 1940. The
      advertisements for hypnotics and sedatives, in The Nederlands Tijdschrift voor
      Geneeskunde (Dutch medical journal) reflected the changes in the vocabulary and
      image promoted by the pharmaceutical companies. In the first two decades, the
      advertisements were sober and to the point, and included the trademark, company
      name, molecular formula and therapeutic properties of the medication. The
      emphasis was on creating a scientific image of reliable symptom control for the
      therapeutic drug. In doing so, the ethical drug companies tried (successfully) to
      distinguish themselves from the producers of patent medicines. Once scientific
      credibility was established, the form and content of the advertisements changed
      significantly. In the late 1920s and 1930s drug companies embraced modern
      advertising techniques, developing a figurative language to address the changing
      beliefs and practices of Dutch physicians. Instead of promoting therapeutic drugs
      as safe and scientific, the emphasis was on their effectiveness in comparison to
      similar drugs. In the process, scientific information was reduced to an
      indispensable standardized minimum, whereby therapeutic drugs were advertised
      according to the latest pharmacological taxonomy rather than molecular formulas.
      The image-making of 'ethical marketing' began during the interwar years when
      marketers applied modern advertising techniques and infotainment strategies. The
      scanty black and white informational bulletins transitioned into colourful
      advertisements. The pharmaceutical companies employed the same medical language
      as used by physicians, so that one word or image in an advertisement would
      suffice for the physician to recognize a drug and its therapeutic properties.
      These developments show the changing relationship between the modern ethical
      pharmaceutical industry and Dutch doctors during the interwar years--from
      rapprochement towards concerted action.

PMID- 22586822
TI  - [Professor Buytendijk's miracle drug. The vitamin preparation Eviunis and the
      risks of scientists doing publicity work].
AB  - The discovery of vitamins at the start of the 20th century not only stimulated
      new areas of scientific research in the field of nutrition and pharmacy; vitamins
      also turned out to be profitable products for new or existing industries.
      Consequently, vitamins drove scientists and commercial vitamin producers into
      each others' arms during the first decades of the century. Several publications-
      by Harmke Kamminga and Sally Horrocks for instance--deal with the causes and
      effects of forms of co-operation between science and industry in the nutritional
      and pharmaceutical sector. They mostly stress--using examples from Great-Britain-
      the interconnected interests from which both profited: industry-sponsored vitamin
      research made vitamins available to a larger public of consumers, with scientists
      authorizing the health claims of the products these companies tried to sell. This
      article shows how Dutch scientists and vitamin producers were concerned with the
      same issue in the inter-war period. Not only does it focus on the interconnected
      interests, but particularly on the conflicts of interests scientists were
      experiencing whilst performing advisory or research work for the industry. The
      article singles out E.J.J. Buytendijk, nowadays remembered for his pioneering
      research in the field of phenomenological psychology after the Second World War,
      and his involvement with the Swiss vitamin preparation Eviunis at the end of the
      nineteen-twenties. Buytendijk actively promoted the introduction of this
      particular preparation on the Dutch market. He was confronted with a growing
      number of critics, however, after tests demonstrated how the preparation could
      hardly sustain any of the claims that had been made with regard to its vitamin
      like performance. Buytendijk's strongest critics accused him of misusing his
      scientific authority to sell a fraudulent product--after all, he that maintained
      his own tests had confirmed Eviunis' claims. A final, state-ordered counter test
      of Eviunis resulted in the ban of the preparation from the Dutch market. However,
      it did not condemn Buytendijks commitment to the product. It only concluded that
      the physiologist had been mistaken in his interpretation of the working of
      Eviunis. Buytendijk's reputation as a vitamin researcher compromised nonetheless,
      because of his spirited commitment to a product that turned out to sell an
      illusion.

PMID- 22586823
TI  - Dry bones.

PMID- 22586824
TI  - Response to Dr. Heir's letter to the editor in CRANIO, April 2011, vol. 29, no.
      2, pp 97-98.

PMID- 22586825
TI  - Another response in support of Dr. Miller's editorial in CRANIO, January 2011,
      vol. 29, no. 1, pp 1-5.

PMID- 22586826
TI  - Bruxism and temporal bone hypermobility in patients with multiple sclerosis.
AB  - In this study, the authors investigated the link between jaw clenching/bruxism
      and temporal bone movement associated with multiple sclerosis (MS). Twenty-one
      subjects participated in this study (10 patients with MS and 11 controls). To
      quantify the change in intracranial dimension between the endocranial surfaces of
      the temporal bones during jaw clenching, an ultrasonic pulsed phase locked loop
      (PPLL) device was used. A sustained jaw clenching force of 100 lbs was used to
      measure the mean change in acoustic pathlength (delta L) as the measure of
      intracranial distance. In the control subjects the mean delta L was 0.27 mm +/-
      0.24. In subjects with MS the mean delta L was 1.71 mm +/- 1.18 (p<0.001). The
      increase in magnitude of bi-temporal bone intracranial expansion was
      approximately six times greater in subjects with MS compared to controls.
      Therefore, jaw clenching/bruxism is associated with more marked displacement of
      the temporal bones and expansion of the cranial cavity in patients with MS than
      in control subjects.

PMID- 22586827
TI  - The effect of the PostureJac on deep cervical flexor endurance: implications in
      the management of cervicogenic headache and mechanical neck pain.
AB  - The convergence of cervical and trigeminal afferents on second-order neurons in
      the trigeminocervical nucleus may refer pain from the upper cervical spine into
      the head and face. Furthermore, "bi-directional interactions" between trigeminal
      and upper cervical afferents may also explain neck symptoms of trigeminal origin
      (e.g., migraine). It is known that cervicogenic headache sufferers present with
      several musculoskeletal changes including poor endurance of the deep cervical
      flexor muscles. These intrinsic muscles of the neck contribute to stabilization
      and protection of the cervical spine and are critical for the control of both
      intervertebral motion and the cervical lordosis. The purpose of this study was to
      determine whether the use of the PostureJac (SomatoCentric Systems, Inc.,
      Toronto, Ontario, Canada), a posture support and exercise jacket, was effective
      in enhancing deep cervical muscle endurance. Forty-five (45) female subjects,
      between the ages of 18 and 40 years, were randomly assigned to three groups
      consisting of the no-treatment control, the treatment-control (table
      stabilization), and the experimental (PostureJac) group. The outcome measure of
      deep cervical flexor muscle endurance was based on the Flexor Endurance Test and
      was recorded in seconds. The results indicated that the PostureJac group was
      superior to the no-treatment control (p=.001) and the treatment-control (p=.004)
      groups in terms of increasing endurance of the deep cervical flexors.
      Consequently, the PostureJac may be a useful therapeutic tool in the management
      of cervicogenic headache and mechanical neck pain.

PMID- 22586828
TI  - Effects of experimental leg length discrepancies on body posture and dental
      occlusion.
AB  - The purpose of this study was to quantitatively evaluate the effects of
      experimental leg length discrepancies on body posture and dental occlusion.
      Thirty asymptomatic subjects (15 males and 15 females, ages 19-33, mean age 25.6
      years) were included in this study and randomly assigned to one of two groups
      based on a table of random numbers. The only difference between group A and group
      B was the sequence of testing. Experimental leg length discrepancies were
      provided by using ten types of insoles with heights ranging from one to ten mm at
      one mm intervals, placed under both feet. The MatScan (Nitta Corp., Osaka, Japan)
      system was used to measure changes in body posture (center of foot pressure: COP)
      while subjects maintained the following three postural positions: 1. natural
      standing posture (control); 2. control with a heel lift under the right foot; or
      3. control with a heel lift under the left foot. The T-Scan II system (Nitta
      Corp., Osaka, Japan) was used to analyze the results of changes in dental
      occlusion (center of occlusal force: COF) in the above-mentioned three postural
      positions. When subjects used a heel lift of six mm or more under the right foot,
      lateral weight distribution (LWD) shifted to the right side compared to the
      control (p<0.05). When a heel lift of four mm or more was used under the left
      foot, LWD shifted to the left side compared to the control (p<0.05). When
      subjects used a heel lift of eight mm or more under the right foot, occlusal
      force shifted to the right side compared to the control (p<0.05). When subjects
      used a heel lift of seven mm or more under the left foot, occlusal force shifted
      to the left side compared to the control (p<0.05). Based on these findings, it
      was concluded that leg length discrepancy affected body posture and dental
      occlusion.

PMID- 22586829
TI  - Temporal tendinitis: a modified Levandoski panoramic analysis of 21 cases.
AB  - In 1993, Levandoski published the details of a system to analyze panoramic
      radiographs and especially, the temporomandibular joints. Piedra expanded the
      work of Levandoski to analyze facial and dental asymmetries. In this brief
      treatise, the disorder of temporal tendinitis was explored. A modified Levandoski
      technique was used to compare the lengths of the coronoid and condylar processes
      in an attempt to demonstrate how the panoramic radiograph can be simply used in
      the diagnosis of temporal tendinitis in the retrospective study of 21 such cases.
      CONCLUSIONS: a total of 18 of the 21 coronoid processes (85%) were equal to or
      longer than their condylar process counterparts, thus indicating that a panoramic
      radiograph may be useful in the diagnosis of temporal tendinitis.

PMID- 22586830
TI  - Evaluation of the effects of temporomandibular joint disk displacement and its
      progression on dentocraniofacial morphology in symptomatic patients using lateral
      cephalometric analysis.
AB  - The aim of this study was to evaluate the effects of disk displacement (DD) and
      its progression on dentocraniofacial morphology in symptomatic patients and
      compare the results with asymptomatic volunteers. Skeletal and dental Class I
      female patients with DD, diagnosed using magnetic resonance imaging (MRI) and
      lateral cephalometric analysis were included in the study. Subjects were grouped
      as follows: control group with bilateral normal disk position (group 1, n=12),
      unilateral DD with reduction (group 2, n=16), bilateral DD with reduction (group
      3, n=26), unilateral DD without reduction (group 4, n=12), and bilateral DD
      without reduction (group 5, n=8). Thirty-two (32) cephalometric variables were
      measured, and statistically significant differences were found in 11. Dental and
      soft tissue measurements did not reveal any differences, but variables related to
      the mandible showed statistically significant differences. Progression of DD was
      associated with an increase in all angular measurements related to vertical
      skeletal relationships and articular angle and a decrease in the ratio of
      posterior face height to anterior face height indicating clockwise rotation of
      the mandible. Similarly, the height of ramus was decreased with the progression
      of DD. The results of this study demonstrated that the presence of DD in skeletal
      Class I female patients effects facial morphology, and its progression makes the
      differences more significant and remarkable. These results emphasize the
      importance of early diagnosis and treatment in the management of DD.

PMID- 22586831
TI  - Atypical odontalgia: a systematic review following the evidence-based principles
      of dentistry.
AB  - Atypical odontalgia (AO) is a severe and persistent pain involving controversial
      pathophysiological mechanisms and clinical management. Presented here is a
      systematic review of the literature on AO, using the SORT criteria (Strength of
      Recommendation Taxonomy) to assess the level of evidence and the quality of
      randomized clinical trials (RCT). A total of 54 articles were obtained of which
      34 belonged to level 3 evidence, 17 to level 2, and 3 to level 1. Of these, only
      8 RCT had an average quality of four points. The main finding of this systematic
      review is that only a few studies have systematically evaluated AO. It also
      determines a strength recommendation of level B to the theory of neuropathic
      origin of pain in AO and strength of recommendation level C for the
      pharmacological management of this condition. The aim of this study was to carry
      out a systematic review of the published literature on AO in order to determine
      the physiopathology and treatment based on the level of scientific evidence and
      following the evidence-based principles of dentistry.

PMID- 22586832
TI  - Temporomandibular joint disk fracture: a case report.
AB  - A case of a patient with a fracture of the temporomandibular joint (TMJ) disk is
      reported. The patient presented with posterior bilateral open-bite and difficulty
      to chew due to lack of contact between the posterior teeth. Diagnosis of disk
      fracture of the right TMJ was made based on magnetic resonance imaging (MRI),
      with posterior displacement of the posterior fragment of the disk, causing the
      posterior open-bite, and anterior displacement of the anterior fragment of the
      disk. TMJ manipulation failed to reposition the posterior fragment of the disk,
      and the patient refused to undergo TMJ arthroscopy to try to remove it. After
      four months, the posterior open-bite was reduced, probably because of remodeling
      of the posterior TMJ capsule and extrusion of the molars and premolars. Contact
      with the patient was lost after that time.

PMID- 22586833
TI  - A case of refractory perforation at the floor of the mouth with ectopic bone
      formation.
AB  - Although most fistulae are not problematic, surgeons occasionally encounter
      recurrent and/or refractory fistulae in the field of oral and maxillofacial
      surgery. In this case report, the authors describe a case in which a patient
      experienced a recurrent and refractory fistula or perforation at his oral floor
      through the submandible, with heterotopic bone formation arising on both sides of
      the mylohyoid line. These heterotopic bones were connected to each other, forming
      a bone bridge at the center of the oral floor. A fistulectomy and wound closure
      with a tongue flap was successful. The perforation has not recurred after over
      four years of follow-up, and the bone bridge is still present.

PMID- 22586834
TI  - Temporomandibular disorders: A position paper of the International College of
      Cranio-Mandibular Orthopedics (ICCMO).
AB  - PURPOSE: Two principal schools of thought regarding the etiology and optimal
      treatment of temporomandibular disorders exist; one physical/functional, the
      other biopsychosocial. This position paper establishes the scientific basis for
      the physical/functional. THE ICCMO POSITION: Temporomandibular disorders (TMD)
      comprise a group of musculoskeletal disorders, affecting alterations in the
      structure and/or function of the temporomandibular joints (TMJ), masticatory
      muscles, dentition and supporting structures. The initial TMD diagnosis is based
      on history, clinical examination and imaging, if indicated. Diagnosis is greatly
      enhanced with physiologic measurement devices, providing objective measurements
      of the functional status of the masticatory system: TMJs, muscles and dental
      occlusion. The American Alliance of TMD organizations represent thousands of
      clinicians involved in the treatment of TMD. The ten basic principles of the
      Alliance include the following statement: Dental occlusion may have a significant
      role in TMD; as a cause, precipitant and/or perpetuating factor. Therefore, it
      can be stated that the overwhelming majority of dentists treating TMD believe
      dental occlusion plays a major role in predisposition, precipitation and
      perpetuation. While our membership believes that occlusal treatments most
      frequently resolve TMD, it is recognized that TMD can be multi faceted and may
      exist with co-morbid physical or emotional factors that may require therapy by
      appropriate providers. The International College of Cranio-Mandibular Orthopedics
      (ICCMO), composed of academic and clinical dentists, believes that TMD has a
      primary physical/functional basis. Initial conservative and reversible TMD
      treatment employing a therapeutic neuromuscular orthosis that incorporates
      relaxed, healthy masticatory muscle function and a stable occlusion is most often
      successful. This is accomplished using objective measurement technologies and
      ultra low frequency transcutaneous electrical neural stimulation (TENS).
      CONCLUSION: Extensive literature substantiates the scientific validity of the
      physical/functional basis of TMD, efficacy of measurement devices and TENS and
      their use as aids in diagnosis and in establishing a therapeutic neuromuscular
      dental occlusion. CLINICAL IMPLICATIONS: A scientifically valid basis for TMD
      diagnosis and treatment is presented aiding in therapy.

PMID- 22586835
TI  - Physical capital and the embodied nature of income inequality: gender differences
      in the effect of body size on workers' incomes in Canada.
AB  - This study assesses the effects of body size--measured using the body mass index-
      on the income attainment of female and male workers in Canada. Using data from a
      national representative sample of Canadians, multivariate analyses show that, for
      female workers, the body size-income relationship is negative. However, for male
      workers, the body size-income relationship is positive and nonlinear. Using
      Bourdieu's conceptualization of physical capital, and Shilling's extension of it,
      it is argued that these results are suggestive of the relative importance of body
      size to the production and continuation of gender income inequality in Canada.

PMID- 22586836
TI  - Moral codes of mothering and the introduction of welfare-to-work in Ontario.
AB  - In this paper, I trace how the reform of social assistance in Ontario, especially
      the post-1990s enforcement of lone mothers' employability via welfare-to-work
      programs, parallels shifts in dominant moral codes of mothering, from "mother
      carer" to "mother-worker." Additionally, I use this case as an entry point to
      consider the implications of public and policy allegiance to these moral codes
      for all mothers. The central argument I make is that the introduction of welfare
      to-work programs in Ontario did not occur in a neoliberal state-sanctioned vacuum
      but also involved the circulation of ideas about moral mothering outside of
      policy into policy.

PMID- 22586837
TI  - Socioeconomic status and cumulative disadvantage processes across the life
      course: implications for health outcomes.
AB  - Given the complexity surrounding various interactions among health determinants
      and the challenge of being able to adequately describe the dynamic processes
      through which health determinants have their effects, the purpose of this paper
      is to provide a conceptual overview demonstrating the effects of socioeconomic
      status and cumulative disadvantage on producing health disparities across the
      life course. The idea underlying cumulative disadvantage is that socioeconomic
      based health inequalities will increase across the life course, mostly because of
      differential exposure to risk factors and access to protective resources. The
      advantage of life course sociology is its consideration of early life
      experiences, and the social and historical context of their occurrences, as
      important contingencies in producing these systematic socioeconomic differences
      in health gradients.

PMID- 22586838
TI  - [The Galenic content of Isaac Beeckman's medical ideas (1617-1629)].
AB  - The Journal tenu par Isaac Beeckman de 1604 a 1634 has been studied in the
      history of the seventeenth-century scientific revolution following the theme of
      Isaac Beeckman's physical mathematical mechanistic view, his proto-molecular
      theory and his atomistic Lucretian influence. This article goes deeper into the
      medical ideas of the Journal: how Isaac Beeckman (1588-1637) settles the
      structure of living matter according to his intensive reading of Galen. It
      develops a different analysis from the traditionally triumphalist approach in the
      history of science, focused on the victory of Cartesian mechanism, particularly
      in the history of medicine taking up Galenism very briefly because of its
      obsolete physiology. The Galenic corpus inside Isaac Beeckman's Journal consists
      of the many commentaries of Galen which Beeckman has put down in writing since
      1616 until 1627, after when the passages linked to Galen became fewer. Isaac
      Beeckman's study of Galenic medicine is analyzed according to three approaches:
      the teleological dimension of Galenism showing up the organic conception of human
      body corresponding to the divine Providence and consistent with Beeckman's
      Calvinist belief, the physiologic angle of Galenism, based on natural faculties,
      stressing the purely speculative aspect of Beeckman's commentaries, while the
      pathologic and therapeutic angle supports the Hippocratic humourism influence.

PMID- 22586839
TI  - ['The political world puzzle'. Ernst Haeckel and the German liberalism 1859
      1900].

PMID- 22586840
TI  - Calling controversy: assessing synthetic biology's conflict potential.
AB  - Will synthetic biology elicit controversies similar to those of genetically
      modified crops before? Maybe, but where exactly are the analogies, and how can we
      gain substantial insights rather than mere guesses? We argue that as well as the
      intrinsic properties of the technologies at stake, the context of their
      implementation is decisive. To assess mechanisms of past and potential
      controversies, an investigative tool is presented. The Gate Resonance model,
      derived from older models of societal conflict, allows the identification of key
      elements of conflict generating processes. In monitoring the developing debate on
      synthetic biology using this model, analogies to the case of genetically modified
      crops appear less convincing. So far, there are only few indications that a
      controversy is imminent.

PMID- 22586841
TI  - Synthetic biology in the view of European public funding organisations.
AB  - We analysed the decisions of major European public funding organisations to fund
      or not to fund synthetic biology (SB) and related ethical, legal and social
      implication (ELSI) studies. We investigated the reaction of public organisations
      in six countries (Austria, France, Germany, the Netherlands, Switzerland and the
      U.K.) towards SB that may influence SB's further development in Europe. We
      examined R&D and ELSI communities and their particular funding situation. Our
      results show that the funding situation for SB varies considerably among the
      analysed countries, with the U.K. as the only country with an established funding
      scheme for R&D and ELSI that successfully integrates these research communities.
      Elsewhere, we determined a general lack of funding (France), difficulties in
      funding ELSI work (Switzerland), lack of an R&D community (Austria), too small
      ELSI communities (France, Switzerland, Netherlands), or difficulties in linking
      existing communities with available funding sources (Germany), partly due to an
      unclear SB definition.

PMID- 22586842
TI  - "Knight in shining armour" or "Frankenstein's creation"? The coverage of
      synthetic biology in German-language media.
AB  - Although still a side issue in the German-language media, attention towards
      synthetic biology has risen clearly during the last years, in line with the first
      applications being presented. This paper presents findings from a content
      analysis of synthetic biology coverage in German-language media over the years
      2004-2009. In the media, synthetic biology is not clearly separated from gene
      technology. News value is attributed to established categories such as persons
      and events. Many metaphors and analogies used in describing gene technology can
      also be found in the coverage of synthetic biology; however, engineering
      metaphors are more prominent. In addition, playfulness constitutes an aspect
      rarely found in genetic engineering coverage. Overall, the picture emerging is
      ambivalent, which leaves prospects for the further development of public debate
      ambiguous.

PMID- 22586843
TI  - Consequences of media information uptake and deliberation: focus groups' symbolic
      coping with synthetic biology.
AB  - Whenever a new, potentially controversial technology enters public awareness,
      stakeholders suggest that education and public engagement are needed to ensure
      public support. Both theoretical and empirical analyses suggest, however, that
      more information and more deliberation per se will not make people more
      supportive. Rather, taking into account the functions of public sense-making
      processes, attitude polarisation is to be expected. In a real-world experiment,
      this study on synthetic biology investigated the effect of information uptake and
      deliberation on opinion certainty and opinion valence in natural groups. The
      results suggest (a) that biotechnology represents an important anchor for sense
      making processes of synthetic biology, (b) that real-world information uptake and
      deliberation make people feel more certain about their opinions, and (c) that
      group attitudes are likely to polarise over the course of deliberation if the
      issue is important to the groups.

PMID- 22586844
TI  - Commentary: Looking for conflict and finding none?

PMID- 22586845
TI  - Rhetoric, power and legitimacy: a critical analysis of the public policy disputes
      surrounding stem cell research in Australia (2005-6).
AB  - In December 2006, the Australian Parliament liberalized regulation governing stem
      cell research. This decision and preceding legislative review generated
      considerable public debate, which centred on objections to the deliberate
      creation and destruction of human embryos for research purposes. This paper draws
      on qualitative research conducted on the public debate surrounding this policy
      episode. The aim of this research was to examine how science and scientific
      knowledge are mobilized by participants in these debates to support their
      arguments. Data were collected from 109 newspaper opinion editorials as well as
      23 in-depth interviews and examined using qualitative content and thematic
      analysis. Results of this analysis depict science as a rhetorical, moral and
      political resource that provides opportunities for participants to gain
      legitimacy, negotiate meaning and assert authority in the public domain. The
      mobilization of science in public discourse is discussed along with suggestions
      that are aimed at encouraging greater transparency and inclusiveness in public
      debates around contested science and emergent technologies.

PMID- 22586846
TI  - Severe acute respiratory syndrome (SARS) and the rhetorical construction of "bad"
      scientific work.
AB  - How are secondary accounts of "bad" scientific practice constructed? How do they
      engage with the primary data produced by "bad" scientists? And what happens to
      those primary data as generations of secondary accounts purporting to describe
      them accumulate? This paper addresses such questions via a case study of Dr.
      Hong, a microbiologist accused of "bad" scientific practice by numerous secondary
      accounts of the 2003 SARS outbreak. Bringing Hong's own account of his own
      actions into dialogue with one of the most influential secondary accounts of his
      actions, the paper highlights the gross disparity between the two. Having argued
      that the rhetorical structuring of the secondary account is, ultimately,
      responsible for Hong's characterisation as a "bad" scientist, it then moves to
      explore how subsequent accounts developed their own characterisations. What
      becomes clear is that as secondary accounts began feeding off one another,
      references to Hong's account disappeared. Aided by the concepts of the
      "vanishing" and the "phantasm", the paper concludes with a consideration of how
      this process left Hong's work with a very peculiar form of existence.

PMID- 22586847
TI  - Organ economy: organ trafficking in Moldova and Israel.
AB  - Organ trafficking is an illegal means of meeting the shortage of transplants. The
      activity flourishes for several interacting reasons, such as medical needs,
      poverty and criminality. Other factors are fundamental conceptual structures such
      as the dream of the regenerative body as well as the view of the body as an
      object of utility and an object of value. The article aims to go behind the
      normative discussions that usually surround organ trafficking. Why this is
      happening, and what the societal consequences are, is examined through
      ethnographic fieldwork. The focus is on the shadow economies that govern
      existence and in which people, goods, weapons, money, bodies, etc. constitute
      components of the global market.

PMID- 22586849
TI  - The impact of molecular techniques on cytology.

PMID- 22586848
TI  - Who is willing to pay for science? On the relationship between public perception
      of science and the attitude to public funding of science.
AB  - This article examines the relationship between the general public's understanding
      of science and the attitude towards public funding of scientific research. It
      applies a multivariate and discriminant analysis (Wilks' Lambda), in addition to
      a more commonly used bivariate analysis (Cramer's V), to data compiled from the
      Third National Survey on the Social Perception of Science and Technology in Spain
      (FECYT, 2006). The general conclusion is that the multivariate analysis produces
      information complementary to the bivariate analysis, and that the variables
      commonly applied in public perception studies have limited predictive value with
      respect to the attitude towards public funding of scientific research.

PMID- 22586850
TI  - Best practices in phlebotomy... in an ACO environment.

PMID- 22586851
TI  - Acquiring a new analyzer.

PMID- 22586852
TI  - New HIV algorithm holds promise.

PMID- 22586853
TI  - Genomics, proteomics, cytomics, and genetic.

PMID- 22586854
TI  - Lab construction projects: a guide to a smoother ride.

PMID- 22586855
TI  - Barcode specimen collection improves patient safety.

PMID- 22586856
TI  - Barcoding: the way to patient safety.

PMID- 22586857
TI  - Formaldehyde shipments: avoid potential pitfalls.

PMID- 22586858
TI  - The future of laboratory developed tests.

PMID- 22586859
TI  - Group B strep disease in the newborn.

PMID- 22586860
TI  - A journey through the prescriptions.

PMID- 22586861
TI  - The pharmacopoeial handbook Sammu sikinsu--an edition.

PMID- 22586862
TI  - [Some plants found in Mesopotamia].

PMID- 22586863
TI  - Getting it right for children, young people and families.

PMID- 22586864
TI  - Reducing cot death by half.

PMID- 22586865
TI  - Training health visiting support staff to detect likelihood of possible postnatal
      depression.
AB  - Community nursery nurses (CNNs) and health visiting assistants (HVAs) are
      increasingly working and supporting health visitors (HVs) within clinical
      settings. The acute shortage of HVs and increased workloads has resulted in
      routine services normally provided by HVs, such as detection/screening for
      postnatal depression, no longer being offered. A training programme for CNNs and
      HVAs in the use of detector questions in assisting the possible detection of
      women at risk of PND was completed by eight CNNs and eight HVAs. Twelve trainees
      consolidated the taught sessions involving specific learning outcomes and
      satisfactory completion of a designated competency framework within the clinical
      setting at the six-to-eight-week child health review in 15 GP practices. HVs
      provided mentorship and assessment within this clinical environment. The
      evaluation suggests that trainees valued the training, and with supervision CNNs
      and HVAs become comfortable in providing this additional service within health
      visiting teams.

PMID- 22586866
TI  - Health visitors' needs--national perspectives from the Restorative Clinical
      Supervision Programme.
AB  - The restorative clinical supervision programme has been delivering supervision
      for the last 18 months to over 600 health visitors within trusts across the UK.
      This opportunity has allowed the supervision team to work with individual
      organisations to identify the key issues with which health visiting teams are
      struggling, and provide effective solutions to reduce staff stress, encourage
      retention and increase job satisfaction. This paper offers an overview of the
      consistent themes that health visitors are attempting to resolve and of how
      restorative supervision supports professionals working with complex families to
      manage these difficulties.

PMID- 22586867
TI  - Parent perspectives of clinical psychology access when experiencing distress.
AB  - Around 20 to 30% of parents experience mental health difficulties within their
      child's first year, but only a small proportion go on to access specialist
      services. This is despite growing evidence around the positive benefits of
      psychosocial interventions for both parents and children. Previous research
      highlights facilitators and barriers to generic healthcare services for mothers
      with postnatal depression. The current study adopted a qualitative methodology to
      explore parents' own perceptions of the barriers and facilitators to clinical
      psychology specifically. Seven women took part in the study, most of whom had no
      previous involvement with specialist mental health services. A thematic analysis
      of interview data suggested six key themes in relation to the research question:
      'The importance of connecting', 'Pressing the danger button', 'I'm not mad',
      'More round care', 'Psychological distress as barrier' and 'Making space, making
      sense'. These are presented alongside a consideration of the clinical
      implications for community-based practitioners, including clinical psychologists.

PMID- 22586868
TI  - Implementing a healthy eating programme: changing children's eating habits for
      life.

PMID- 22586869
TI  - Pay, pensions and holidays.

PMID- 22586870
TI  - The blank piece of paper...

PMID- 22586871
TI  - Pseudoephedrine and methamphetamine and the legal opposition.

PMID- 22586872
TI  - Question: What are the 5 most common systemic causes of pruritus without primary
      skin changes in adults?

PMID- 22586874
TI  - Heart attack symptoms in women.

PMID- 22586875
TI  - Warning signs of heart failure.

PMID- 22586873
TI  - Patient safety and medical errors: a focus on care transitions of the vulnerable
      older patient.
AB  - The delivery of quality medical care includes the reduction of patient exposure
      to potentially adverse events that can lead to unnecessary suffering and
      disability or possibly death. Elderly patients residing in long-term care
      facilities are often transferred to emergency rooms for evaluation and management
      of an exacerbation of a chronic medical condition or an acute injury. Studies
      show that nursing home residents may be at higher risk for experiencing adverse
      medical events that lead to serious patient safety and quality of care concerns.
      These risks may be attributable to lack of effective communication among
      caregivers who help transition patients across acute care settings. This article
      reviews some of the challenges inherent in a complex system of care as elderly
      patients traverse healthcare settings and discusses the need to create system
      wide changes that will help prevent medical errors and improve patient safety for
      an at risk vulnerable population.

PMID- 22586876
TI  - The use of electronic portfolios in nurse anesthesia education and practice.

PMID- 22586877
TI  - Role of splenic artery partial embolization in a patient with portal hypertension
      and pancytopenia undergoing hysterectomy under anesthesia.
AB  - Management of a patient with portal hypertension and hypersplenism who is
      scheduled for elective surgery is a challenge for anesthesia providers. We report
      a case that was scheduled for elective surgery in which preoperative splenic
      artery embolization improved the hematologic parameters. A 32-year-old woman was
      scheduled for total abdominal hysterectomy for multiple fibroids and menorrhagia
      with pancytopenia. She also had diagnoses of chronic liver disease with cirrhotic
      changes, portal hypertension, and grade IV Manageesophageal varices with
      hepatosplenomegaly. In view of pancytopenia, splenic artery partial embolization
      was done preoperatively. Her hematologic parameters improved, and she underwent
      surgery under general anesthesia with intrathecal morphine analgesia,
      uneventfully. The condition of patients with portal hypertension with associated
      hypersplenism and pancytopenia who are scheduled for elective surgery can be
      optimized with preoperative partial splenic artery embolization.

PMID- 22586879
TI  - Total artificial heart freedom driver in a patient with end-stage biventricular
      heart failure.
AB  - Approximately 5.7 million people in the United States have a diagnosis of heart
      failure, and more than 3,100 patients are awaiting a heart transplant. A
      temporary total artificial heart (TAH-t, SynCardia Systems Inc, Tucson, Arizona)
      is approved by the US Food and Drug Administration (FDA) as a bridge to
      transplant in patients at risk of dying of biventricular heart failure.
      Currently, TAH-t recipients awaiting transplant are hospital-bound and attached
      to a large pneumatic driver. In 2010, the FDA gave conditional approval for an
      Investigational Device Exemption clinical study of the portable Freedom driver
      (SynCardia). This case report describes a 61-year-old man admitted with acute
      decompensated heart failure, which progressively worsened, eventually requiring
      implantation of a TAH-t. Following stabilization, the patient was switched to the
      Freedom driver. After the patient and his wife proved competence in managing the
      device, they were able to take several daylong excursions outside the hospital.
      The patient considered discharge from the hospital while awaiting a transplant
      but ultimately received a heart transplant while still an inpatient. Higher rates
      of survival to transplant have already been proved with the TAH-t. Potential
      benefits for the portable Freedom driver include increased mobility, decreased
      cost, and improved quality of life.

PMID- 22586878
TI  - Effects of topical lidocaine on successful extubation time among patients
      undergoing elective carotid endarterectomies.
AB  - Little research has been done on the effects that topical intratracheal
      anesthesia have on the length of time required to successfully extubate patients
      after surgical interventions. This retrospective case-control study, using a
      convenience sample (n = 100 patients), explored the effects of using topical
      lidocaine laryngotracheal anesthesia injected into the adult trachea before
      insertion of the endotracheal tube on patients undergoing surgical treatment for
      blockage of the carotid artery. Both descriptive and inferential analyses were
      performed to evaluate differences among all variables. Multiple linear regression
      was also performed while adjusting for the confounding factors (age, gender, and
      smoking status). Results revealed that the use of lidocaine laryngotracheal
      anesthesia during induction of anesthesia prolonged the mean times for
      postoperative removal of the endotracheal tube by nearly 2 minutes. Extended time
      for removal of endotracheal tubes may lead to increased costs to the healthcare
      institution and to the patient, which in turn may lead to dissatisfaction within
      healthcare teams and possibly to patient discontent with care provided.

PMID- 22586880
TI  - Rapunzel syndrome in a pediatric patient: a case report.
AB  - This case report describes a 2.5-year-old girl who was hospitalized with
      complaints of abdominal pain and vomiting for 2 days. Abdominal ultrasound
      revealed small bowel-to-small bowel intussusception. Diagnostic laparoscopic
      assisted exploration of the abdomen revealed 4 separate intestinal
      intussusceptions along with multiple dark intraluminal masses within the small
      intestine. Laparoscopic reduction of the intussusceptions was unsuccessful.
      Laparotomy allowed palpation of the entire small intestine with extraction of the
      masses, which were found to be human hair (trichobezoars). The intussusceptions
      were reduced, and the multiple masses were removed through a single enterotomy.
      The child recovered following surgery and was discharged home to her family. The
      surgeon counseled the parents before discharging the patient and recommended
      follow-up counseling for their child. The parents were given information about
      trichophagia and strategies to reduce the behavior in their child. A
      comprehensive literature review revealed this to be the youngest reported case of
      intussusception and Rapunzel syndrome due to trichobezoars.

PMID- 22586881
TI  - Opioid abuse among nurse anesthetists and anesthesiologists.
AB  - Abuse and dependency on potent opioids have long been recognized as problems
      among nurse anesthetists and anesthesiologists. Research has provided insight
      into the incidence of abuse, risk factors associated with this type of
      dependency, identification of an impaired provider, treatment for abuse and
      dependency, and prevention strategies. Although several factors influence the
      development of abuse and dependency, access to potent opioids likely has a large
      role. This access also makes returning to practice while in recovery extremely
      difficult because the temptation for relapse continually surrounds a recovering
      anesthesia provider. There is research supporting successful reentry of
      anesthesia providers into the practice of anesthesia; however, research also
      reveals high relapse rates among anesthesia providers who return to the practice
      of anesthesia. This article reviews the literature regarding opioid abuse and
      dependency among nurse anesthetists and anesthesiologists and offers implications
      for future research.

PMID- 22586882
TI  - Anesthetic-induced anaphylaxis.
AB  - The purpose of this course is to update nurse anesthetists about anesthetic
      induced anaphylaxis. This course discusses the pathophysiologic process of
      anaphylaxis with descriptions of the allergic immune response and the mediators
      and mechanisms of mast cell activation. The preoperative identification of
      patients at high risk and the assessment of potential anesthetic triggers of a
      hypersensitivity and/or allergic reaction are prudent strategies to minimize the
      risk of anaphylaxis. Other practices recommended for clinicians include
      suggestions for anesthetic management to decrease threat of an allergic response
      in high-risk patients. Furthermore, the identification of the severity grade of
      hypersensitivity reactions and the appropriate treatment of perioperative
      anaphylaxis is discussed. In addition, postoperative and follow-up interventions,
      including testing for patients who have had an anesthetic-induced
      hypersensitivity reaction, are considered.

PMID- 22586883
TI  - [Miracle healers of the Weimar Republic. Protagonists, methods of healing and
      status within the health care system].

PMID- 22586884
TI  - [Miracle healers of the Weimar Republic. Protagonists, methods of healing and
      status within the health care system. The miracle healers].

PMID- 22586886
TI  - Hippocrates, on the art of medicine. Introduction.

PMID- 22586888
TI  - On the art of medicine.

PMID- 22586889
TI  - Hippocrates, On the art of medicine. Commentary.

PMID- 22586890
TI  - [Dr. Michiharu Matsuoka, founder of the Department of Orthopaedic Surgery, Kyoto
      University, and his achievements. (Part 7: The academic carrier of Dr. Michiharu
      Matsuoka--from elementary school to the graduate school, Imperial University of
      Tokyo)].
AB  - The background of the higher education of Dr. Michiharu Matsuoka shown on the
      official resume was disclosed by Dr. Kazuo Naito in 1986, but the courses of the
      elementary and secondary schools were not described in it. In regard to his lower
      educational courses, the author referred to the laws and regulations issued by
      the Ministry of Education of the Japan Government and the Yamaguchi Prefectural
      Office. Those were often revised with times. The author presumed the elementary
      school (Murozumi Primary School [the first established primary school at the
      birthplace; Murozumi, Hikari-City, Yamaguchi Prefecture]) and middle schools
      (Prefectural Yamaguchi Middle School and Yamaguchi High School) to which he had
      been admitted. These presumptions were made to explain his whole educational
      course without unreasonableness. After finishing the first school year of the
      Yamaguchi High School, he was transferred to the Preparatory Course of the
      Yamaguchi Higher School (Yamaguchi Koto Chugakko, Yoka), because of the amendment
      of the educational system. Then he was transferred to the Preparatory Course of
      the Daisan Higher School (Daisan Koto Chugakko, Yoka), and to the Preparatory
      Course of Daiichi Higher School (Daiichi Koto Chugakko, Yoka). After his
      graduation from the Regular Course of the Daiichi Higher School (Daiichi Koto
      Chugakko, Honka), he was admitted to the Medical College of the Imperial
      University from which he graduated in 1897. In addition, he was a medical student
      of the Graduate School of the Imperial University of Tokyo just before he left
      Japan for studying abroad. The whole academic carrier of Dr. Matsuoka is not only
      clearly clarified, but it is also indicated that he was one of the successful
      examples of the educational system proposed by Yamaguchi Prefecture in Meiji era
      which articulated the local primary and middle schools with the Imperial
      University of Tokyo.

PMID- 22586891
TI  - [Dissemination of medical information in Europe, the USA and Japan, 1850-1870:
      focusing on information concerning the hypodermic injection method].
AB  - Modern medicine was introduced in Japan in the second half of the nineteenth
      century. In order to investigate this historical process, this paper focuses on
      the dissemination of information of a new medical technology developed in the mid
      nineteenth century; it does so by making comparisons of the access to medical
      information between Europe, the USA and Japan. The hypodermic injection method
      was introduced in the clinical field in Europe and the USA as a newly developed
      therapeutic method during the 1850s and 1870s. This study analyzed information on
      the medical assessments of this method by clinicians of these periods. The
      crucial factor in accumulating this information was to develop a worldwide inter
      medical communication circle with the aid of the medical journals. Information on
      the hypodermic injection method was introduced in Japan almost simultaneously
      with its introduction in Europe and the USA. However, because of the geographical
      distance and the language barrier, Japanese clinicians lacked access to this
      worldwide communication circle, and they accepted this new method without
      adequate medical technology assessments.

PMID- 22586892
TI  - [Medical history of Martin Luther].
AB  - Martin Luther achieved great success in religious reformation, though he was said
      to have suffered from many kinds of diseases during his lifetime. Unfortunately,
      however, his medical history has never been reported in Japan. Since the second
      half of his thirties, he was suffering from severe constipation, causing
      hemorrhoids and anal prolapse. At the beginning of his forties he had vertigo,
      tinnitis and headaches, which were the signs of chronic purlent otitis media and
      ended in left otorrhea and pyorrhea of the left mastoiditis. Nearly at the same
      time, he started to suffer from anginal pain, colic and dysuria due to urinary
      uric acid stones, gout and left leg ulcer, which were all caused by metabolic
      syndromes. The last 1/3 of his life was affected by the shadow of diseases, and
      his religious activities were frequently disturbed. He died from myocardial
      infarction at the age 63, in February 1546.

PMID- 22586893
TI  - [The medical studies in the modern Greek academic journal "Hermes o Logios"].

PMID- 22586894
TI  - [Explanation and translation of Galen's "de Usu Partium" (see text) book 1].

PMID- 22586895
TI  - [Research on the Ikeda Documents (41)].

PMID- 22586896
TI  - [Investigation of antitumor substance from Trichoderma].
AB  - The effect of L-lysine-alpha-oxidase from Trichoderma harzianum Rifai on the
      functional activity of T-lymphocytes was investigated. It was shown that in a
      dose of 35 units/kg administered parentally the enzyme had no suppressive effect
      on the T-lymphocyte functional activity. An inhibitory effect of L-lysine-a
      oxidase on some indices of the macrophages functional activity was observed. L
      Lyzine-alpha-oxidase had a selective lymphotropic action and showed no mytostatic
      activity, which is in favour of the enzyme vs. other antitumor agents.

PMID- 22586897
TI  - [Investigation of molecular mechanisms of aminoglycoside resistance in
      Salmonella].
AB  - The spread of aminoglycoside resistance phenotype and respective genetic
      resistance determinants was evaluated in 243 Salmonella strains isolated within
      1948-2010 and stored in the Culture Collection of the Russian State Research
      Institute for Control, Standardization and Certification of Veterinary
      Preparations (Moscow). The Salmonella strains showed resistance to streptomycin
      and gentamicin in 3.7% (n = 9) and 0.8% (n = 2) of the isolates respectively.
      Intermediate resistance to streptomycin was recorded in 9.9% (n = 24) of the
      isolates. To detect the genes responsible for the aminoglycoside resistance,
      primers for aadA1, aadA2, aadB, aphA1, aphA3, sat, strA, strB, aphA, aacC, rmtB,
      armA and rpsL genes amplification and sequencing were designed. The strains with
      lower susceptibility to streptomycin harbored aadA1, aadA2, strA, strB resistance
      genes encoding enzymes for aminoglicoside modification and rpsL mutant allele
      (K42N, G91D). Genetic mechanisms able to explain the gentamicin resistance
      development were not detected. Some strains carried genetic markers of
      streptomycine resistance but had no clinically sufficient resistance to it. In
      this regard, genetic testing is essential for prevention of drug resistance
      spreading due to horizontal transfer of genes in microbial population.

PMID- 22586898
TI  - [Efficacy of enterocin S760 in treatment of mice with anthrax infection due to
      Bacillus anthracis M-71].
AB  - The therapeutic efficacy of enterocin S760, a broad spectrum antimicrobial
      peptide produced by Enterococcus faecium LWP760 was tested on mice infected with
      Bacillus anthracis M-71 to induce anthrax (second Tsenkovsky's vaccine).
      Intraperitoneal four-, two- or one-fold administration of the peptide in a dose
      of 25 mg/kg for 10 days for prophylactic (1 hour after the contamination) and
      therapeutic (24 hours after the contamination) purposes prevented or cured the
      infection in 90-100% of the mice versus the 100-percent lethality in the control
      (untreated animals). The antimicrobial activity of enterocin S760 against B.
      anthracis M-71 in vivo correlated with activity in vitro. Enterocin S760 is
      considered a novel promising antimicrobial for the treatment of grampositive and
      gramnegative infections.

PMID- 22586899
TI  - [Estimation of possible use of interferon inductors for prevention of
      postvaccional reactions to TEOVac in animal models].
AB  - The experiments on guinea pigs showed that arbidol administered orally in a
      single dose 24 hours prior vaccination with TEOVAC and ridostin administered in a
      single dose intranasally on the 4th day after the vaccination lowered the vaccine
      virus accumulation in the animal organs and tissue without any effect on the
      vaccine immunogeneity. The results are someway indicative of the possible use of
      the interferon inductors for prevention of postvaccinal reactions to TEOVAC.

PMID- 22586900
TI  - [Ergoferon and improvement of etiopathogenetic therapy of influenza and acute
      respiratore viral infection in adults].
AB  - The therapeutic efficacy and tolerance of ergoferon, an antiviral medication
      combining anti-inflammatory and antihistaminic actions were estimated in the
      treatment of adult patients with influenza and acute respiratory viral infection.
      Ergoferon was shown to stimulate production of endogenous interferon-alpha and
      interferon-gamma and to normalize the T-lymphocyte subpopulation composition and
      histamine level, that made it possible to lower the time of the disease clinical
      signs development and to prevent typical complications and chronic somatic
      pathology exacerbation.

PMID- 22586901
TI  - [Antiviral activity of recombinant interferon-alpha-2b in combination with
      certain antioxidant].
AB  - In vitro activity of interferon-alpha-2b in combination with various antioxidants
      against the influenza virus and Herpes simplex was studied. The standard strains
      and a clinical strain of Herpes simplex isolated from a patient with resistance
      to acyclovir were used. The in vitro studie showed that antioxidants, such as
      alpho-tocoferol acetate (vitamin E), Unithiol and ascorbic acid had a significant
      antiinfluenzae and antiherpetic action on the influenza virus A/H5N1 and Herpes
      simplex variants. They protected up to 100% of the cell monolayer from the virus
      cytopathic effect. The taurin solutions had no antiviral activity irrespective of
      the infection dose. Combinations of interferon-alpha-2b with alpha-tocopherol
      acetate (vitamin E), Unithiol or ascorbic acid showed a significant synergistic
      effect: the antiviral activity of interferon increased several times. The
      antiinfluenza activity of interferon-a-2b in the presence of various
      concentrations of taurin did not change.

PMID- 22586902
TI  - [Therapeutic efficacy of various formulations of cycloferon in the treatment of
      infectious mononucleosis in children].
AB  - One hundred twenty six children at the age of 4 to 7 years with infectious
      mononucleosis were observed. The subjects under the complex therapy were treated
      with cycloferon suppositoria (1st group), intramuscular cycloferon (2nd group) or
      placebo (3rd group). The results demonstrated similar therapeutic efficacy of the
      parenteral cycloferon and rectal suppositoria (a novel cycloferon formulation).

PMID- 22586903
TI  - [Clinical efficacy of cycloferon in complex therapy of infectious mononucleosis
      in pediatrics].
AB  - The results of the cycloferon use in therapy of 80 children at the age of 1 to 15
      years with infectious mononucleosis are presented. The children were divided by
      chance sampling into two comparable groups of 40 subjects each. In the first
      group the children in addition to the standard therapy were treated with
      cycloferon for 10 days, intramuscularly or orally depending on the age. The
      reference group included the patients under the standard therapy alone. The
      efficacy of the drug was evaluated by reduction and more rapid disappearance of
      the main clinical symptoms of the disease. The improvement of certain laboratory
      indices, including those of the liver protein synthesis function were recorded,
      that allowed to reduce the hospitalization term. No side effects of the
      cycloferon use were observed.

PMID- 22586904
TI  - [Present state of in vitro and in vivo studies on efficacy of medical nonspecific
      protective agents with respect to genotype IV coronavirus causing severe acute
      respiratory syndrome].
AB  - The results of the in vitro studies on the efficacy of medical nonspecific
      protective agents from various pharmacological groups showed that some drugs,
      such as velferon, alferon, betaferon, ribavirin and lopinavir were active against
      TOPC virus, that permitted to recommend them for estimation of their activity on
      laboratory animals. The data on the in vivo activity of pharmacological drugs
      with respect to TOPC virus are rather scanty and it is difficult to predetermine
      their efficacy. The danger of TOPC virus latent circulation among wild animals in
      China requires research of new efficient medical agents for protection of the
      people from the pathogen in the Russian Federation.

PMID- 22586906
TI  - Changes in the antioxidant system and level of proinflammatory cytokin IL-1beta
      in the blood patients of sufferi.
AB  - Diabetes mellitus type 1 provokes the development of the oxidative stress,
      accompanied by the increased level of TBA-active products, activation of NO
      synthases and increased production of nitric oxide. Activation of glutathione
      reductase, decrease of the glutathione peroxidase and superoxide dismutases
      activity was observed. This shows a specific disturbance in the functioning of
      the antioxidant defense system and the augmentation in the concentration of one
      of the major first line reacting cytokin (IL-1beta).

PMID- 22586905
TI  - Cytochrome C as an amplifier of ROS release in mitochondria.
AB  - The influence of exogenous cytochrome c on reactive oxygen species (ROS)
      formation and its dependence on mitochondrial permeability transition pore (MPTP)
      opening is studied in rat liver mitochondria. Fluorescent probe
      dichlorofluorescein (DCF) was used. It was shown that MPTP activation by
      increasing concentrations of Ca2+ in the medium results in the increase in
      mitochondrial ROS production and oxygen consumption, but the decrease in matrix
      calcium retention, dependent on the amount of added Ca2+. Cytochrome c in the
      incubation medium does not much influence ROS formation when MPTP opening is
      blocked by cyclosporine A. However, in the presence of cytochrome c MPTP opening
      is accompanied by dramatic increase in ROS production. Steep rise in DCF
      fluorescence because of matrix ROS formation is sensitive to MPTP opening and is
      not resulted from the direct interaction between the probe and cytochrome c
      outside the mitochondria. To explain obtained data the hypothesis is put forward
      that MPTP could serve for ROS exchange between the matrix and the medium where
      heme iron of cytochrome c would act as a catalytic center to enhance ROS
      production. We suppose that apart of its conventional function, cytochrome c
      which is not involved in electron transport, could serve in such way as the
      amplifier of ROS production which in turn would provide a background for the
      development of apoptosis due to MPTP opening.

PMID- 22586907
TI  - Bioprospecting microalgae as potential sources of "green energy"--challenges and
      perspectives (review).
AB  - Microalgae and cyanobacteria are potential foods, feeds, sources of high-value
      bioactive molecules and biofuels, and find tremendous applications in
      bioremediation and agriculture. Although few efforts have been undertaken to
      index the microalgal germplasm available in terms of lipid content, information
      on suitability of strains for mass multiplication and advances in development of
      methods for extraction and generating biofuel are scarce. Our review summarizes
      the potential of microalgae, latest developments in the field and analyzes the
      "pitfalls" in oversimplification of their promise in the years to come.
      Microalgae represent "green gold mines" for generating energy; however, the path
      to success is long and winding and needs tremendous and concerted efforts from
      science and industry, besides political will and social acceptance for overcoming
      the limitations. The major advantages of second generation biofuels based on
      microalgal systems, include their higher photon conversion efficiency, growth all
      around the year, even in wastewaters, and production of environment friendly
      biodegradable biofuels.

PMID- 22586908
TI  - Microalgae biofuel potentials (review).
AB  - With the decrease of fossil based fuels and the environmental impact of them over
      the planet, it seems necessary to seek the sustainable sources of clean energy.
      Biofuels, is becoming a worldwide leader in the development of renewable energy
      resources. It is worthwhile to say that algal biofuel production is thought to
      help stabilize the concentration of carbon dioxide in the atmosphere and decrease
      global warming impacts. Also, among algal fuels' attractive characteristics,
      algal biodiesel is non toxic, with no sulfur, highly biodegradable and relatively
      harmless to the environment if spilled. Algae are capable of producing in excess
      of 30 times more oil per acre than corn and soybean crops. Currently, algal
      biofuel production has not been commercialized due to high costs associated with
      production, harvesting and oil extraction but the technology is progressing.
      Extensive research was conducted to determine the utilization of microalgae as an
      energy source and make algae oil production commercially viable.

PMID- 22586909
TI  - [Enzymatic synthesis of electroconductive biocomposites based on DNA and
      optically active polyaniline].
AB  - Electroconductive interpolymer polyaniline complexes are synthesized on the DNA
      matrix, using the method of oxidative polymerization of aniline with two
      different biocatalyzers: horseradish root peroxidase and micropiroxidase-11
      biomimetic. The spectral characteristics and morphology of the acquired
      biocomposites have been studied. The stereospecificity of the acquired samples of
      interpolymer complexes is shown, depending on the biocatalyzers used. The results
      acquired indicate the important role of a biocatalyzer in the formation of the
      twist direction of an electroconductive polymer spiral on the DNA matrix; i.e.,
      the optical activity of the polymer samples acquired is apparently associated
      with the biocatalyzer properties.

PMID- 22586910
TI  - Enzymatic modification of chitosan with quercetin and its application as
      antioxidant edible films.
AB  - Quercetin, rutin, naringin, hesperidin and chrysin were tested as substrates for
      chloroperoxidase to produce reactive quinones to graft onto chitosan. Quercetin
      and rutin quinones were successfully chemically attached to low molecular weight
      chitosan. The quercetin-modified chitosan showed an enhancement of plastic,
      antioxidant and antimicrobial properties as well as of thermal degradability.
      Finally, chitosan-quercetin films visibly decreased enzymatic oxidation when
      applied to Opuntia ficus indica cladodes.

PMID- 22586911
TI  - Enzymatic synthesis oF L-tryptophan from D,L-2-amino-delta2-thiazoline-4
      carboxylic acid and indole by Pseudomonas sp. TS1138 L-2-amino-delta2-thiazoline
      4-carboxylic acid hydrolase, S-carbamyl-L-cysteine amidohydrolase, and
      Escherichia coli L-tryptophanase.
AB  - L-Tryptophan (L-Trp) is an essential amino acid. It is widely used in medical,
      health and food products, so a low-cost supply is needed. There are 4 methods for
      L-Trp production: chemical synthesis, extraction, enzymatic synthesis, and
      fermentation. In this study, we produced a recombinant bacterial strain pET-tnaA
      of Escherichia coli which has the L-tryptophanase gene. Using the pET-tnaA E.
      coli and the strain TS1138 of Pseudomonas sp., a one-pot enzymatic synthesis of L
      Trp was developed. Pseudomonas sp. TS1138 was added to a solution of D,L-2-amino
      delta2-thiazoline-4-carboxylic acid (DL-ATC) to convert it to L-cysteine (L-Cys).
      After concentration, E. coli BL21 (DE 3) cells including plasmid pET-tnaA,
      indole, and pyridoxal 5'-phosphate were added. At the optimum conditions, the
      conversion rates of DL-ATC and L-Cys were 95.4% and 92.1%, respectively. After
      purifying using macroporous resin S8 and NKA-II, 10.32 g of L-Trp of 98.3% purity
      was obtained. This study established methods for one-pot enzymatic synthesis and
      separation of L-Trp. This method of producing L-Trp is more environmentally sound
      than methods using chemical synthesis, and it lays the foundations for industrial
      production of L-Trp from DL-ATC and indole.

PMID- 22586912
TI  - Proline dehydrogenase from Pseudomonas fluorescence: gene cloning, purification,
      characterization and homology modeling.
AB  - The gene encoding proline dehydrogenase (ProDH) from Pseudomonas fluorescence was
      isolated using PCR amplification and cloned into pET23a expression vector. The
      expression of the recombinant target enzyme was induced by addition of IPTG. The
      produced His-fusion enzyme was purified and its kinetic properties were studied.
      The 3D structure modeling was also performed to identify key amino acids involved
      in FAD-binding and catalysis. The PCR product contained a 1033 bp open reading
      frame encoding 345 amino acid residue polypeptide chain. SDS-PAGE analysis
      revealed a MW of 40 kDa, whereas the native enzyme exhibited a MW of 40 kDa
      suggesting a monomeric protein. The K(m) and V(max) values of the P. fluorescence
      ProDH were estimated to be 35 mM and 116 micromol/min, respectively. ProDH
      activity was stable at alkaline pH and the highest activity was observed at 30
      degrees C and pH 8.5. The modeling analysis of the three dimensional structure
      elucidated that Lys-173 and Asp-202, which were oriented near the hydroxyl group
      of the substrate, were essential residues for the ProDH activity. This study, to
      our knowledge, is the first data on the cloning and biochemical and structural
      properties of P. fluorescence ProDH.

PMID- 22586913
TI  - Isolation and characterization of feather degrading enzymes from Bacillus
      megaterium SN1 isolated from Ghazipur poultry waste site.
AB  - The SN1 strain of Bacillus megaterium, isolated from soil of Ghazipur poultry
      waste site (India) produced extracellular caseinolytic and keratinolytic enzymes
      in basal media at 30 degrees C, 160 rpm in the presence of 10% feather. Feathers
      were completely degraded after 72 h of incubation. The caesinolytic enzyme was
      separated from the basal media following ammonium sulphate precipitation and ion
      exchange chromatography. We report 29.3-fold purification of protease after Q
      Sepharose chromatography. The molecular weight of this enzyme was estimated to be
      30 kDa as shown by SDS-PAGE and zymography studies. Protease activity increased
      by 2-fold in presence of 10 mM Mn2+ whereas Ba2+ and Hg2+ inhibited it. Ratio of
      milk clotting activity to caseinolytic was found to be 520.8 activity for the 30
      60% ammonium sulphate fraction in presence of Mn2+ ion suggesting potential
      application in dairy industry. Keratinase was purified to 655.64 fold with
      specific activity of 544.7 U/mg protein and 12.4% recovery. We adopted the
      strategy of isolating the keratinolytic and caesinolytic producing microorganism
      by its selective growing in enriched media and found that feather protein can be
      metabolized for production of animal feed protein concentrates.

PMID- 22586914
TI  - Effect of partial pressure of CO2 on the production of thermostable alpha-amylase
      and neutral protease by Bacillus caldolyticus.
AB  - Controlling the concentration of dissolved oxygen is a standard feature in
      aerobic fermentation processes but the measurement of dissolved CO2
      concentrations is often neglected in spite of its influence on the cellular
      metabolism. In this work room air and room air supplemented with 5% and 10%
      carbon dioxide were used for aeration during the cultivation of the thermophilic
      microorganism Bacillus caldolyticus (DSM 405) on starch to produce alpha-amylase
      (E.C. 3.2.1.1) and neutral protease (E.C. 3.4.24.27/28). The increased CO2
      concentrations resulted in a 22% raise in activity of secreted alpha-amylase and
      a 43% raise in protease activity when compared with aeration with un-supplemented
      room air. There was no effect on the final biomass concentration. Furthermore,
      the lag-phase of fermentation was reduced by 30%, further increasing the
      productivity of alpha-amylase production. Determinations of dissolved CO2 in the
      culture broth were conducted both in situ with a probe as well as using exhaust
      gas analysis and both the methods of quantification showed good qualitative
      congruence.

PMID- 22586915
TI  - Rhamnolipid production by Pseudomonas aeruginosa engineered with the Vitreoscilla
      hemoglobin gene.
AB  - The potential of Pseudomonas aeruginosa expressing the Vitreoscilla hemoglobin
      gene (vgb) for rhamnolipid production was studied. P. aeruginosa (NRRL B-771) and
      its transposon mediated vgb transferred recombinant strain, PaJC, were used in
      the research. The optimization of rhamnolipid production was carried out in the
      different conditions of cultivation (agitation rate, the composition of culture
      medium and temperature) in a time-course manner. The nutrient source, especially
      the carbon type, had a dramatic effect on rhamnolipid production. The PaJC strain
      and the wild type cells of P. aeruginosa started producing biosurfactant at the
      stationary phase and its concentration reached maximum at 24 h (838 mg/l(-1)) and
      at 72 h (751 mg l(-1)) of the incubation respectively. Rhamnolipid production was
      optimal in batch cultures when the temperature and agitation rate were controlled
      at 30 degrees C and 100 rpm. It reached 8373 mg l(-1) when the PaJC cells were
      grown in 1.0% glucose supplemented minimal media. Genetic engineering of
      biosurfactant producing strains with vgb may be an effective method to increase
      its production.

PMID- 22586916
TI  - [Prolonged cultivation of an anaerobic bacterial community producing hydrogen].
AB  - This paper studies various methods of long-term maintenance of the process of
      hydrogen evolution during the growth of an aerobic bacterial community on a
      starch-containing environment. When cultured in separable trip fermentation mode
      for 72 days, from 0.10 to 0.23 H2/l of medium/day was formed. The regime of
      regular reseeding lasted more than 100 days, forming an average of 0.81 1 H2/l of
      medium/day. The advantages and disadvantages of different methods of microbial
      hydrogen production during a dark starch fermentation process are presented. From
      the obtained H2 forming microbial communities, we isolated an anaerobic spore
      forming bacterium (strain BF). Phylogenetic analysis of the 16S RNA gene sequence
      of the new strain showed that according to its genotype it belongs to the
      Clostridium butyricum species.

PMID- 22586917
TI  - [Effect of exogenous fatty acids on the growth and production of
      exopolysaccharides of obligately methylotrophic bacterium Methylophilus quaylei].
AB  - Accelerating growth and increasing exopolysaccharide production in obligate
      methylotrophic bacterium Methylophilus quaylei were observed in the presence of
      C12-C18 fatty acids added to the growth media. Sodium oleate was the best growth
      factor. Based on data on the composition of the free fatty acids fraction in the
      cells and the values of the zeta-potential and fluorescence anisotropy of whole
      cells, we suggested that fatty acids were incorporated in the outer membrane of
      M. quaylei.

PMID- 22586918
TI  - [Ratio [13C]/[12C] as an index for express estimation of hydrocarbon-oxidizing
      potential of microbiota in soil polluted with crude oil].
AB  - The hydrocarbon-oxidizing potential of soil microbiota and hydrocarbon-oxidizing
      microorganisms introduced into soil was studied based on the quantitative and
      isotopic characteristics of carbon in products formed in microbial degradation of
      oil hydrocarbons. Comparison of CO2 production rates in native soil and that
      polluted with crude oil showed the intensity of microbial mineralization of soil
      organic matter (SOM) in the presence of oil hydrocarbons to be higher as compared
      with non-polluted soil, that is, revealed a priming effect ofoil. The amount of
      carbon of newly synthesized organic products (cell biomass and exometabolites)
      due to consumed petroleum was shown to significantly exceed that of SOM consumed
      for production of CO2. The result of microbial processes in oil-polluted soil was
      found to be a potent release of carbon dioxide to the atmosphere.

PMID- 22586919
TI  - Construction of the industrial ethanol-producing strain of Saccharomyces
      cerevisiae able to ferment cellobiose and melibiose.
AB  - The gene mel1, encoding alpha-galactosidase in Schizosaccharomyces pombe, and the
      gene bgl2, encoding and beta-glucosidase in Trichoderma reesei, were isolated and
      co-expressed in the industrial ethanol-producing strain of Saccharomyces
      cerevisiae. The resulting strains were able to grow on cellobiose and melibiose
      through simultaneous production of sufficient extracellular alpha-galactosidase
      and beta-glucosidase activity. Under aerobic conditions, the growth rate of the
      recombinant strain GC 1 co-expressing 2 genes could achieve 0.29 OD600 h(-1) and
      a biomass yield up to 7.8 g l(-1) dry cell weight on medium containing 10.0 g l(
      1) cellobiose and 10.0 g l(-1) melibiose as sole carbohydrate source. Meanwhile,
      the new strain of S. cerevisiae CG 1 demonstrated the ability to directly produce
      ethanol from microcrystalline cellulose during simultaneous saccharification and
      fermentation process. Approximately 36.5 g l(-1) ethanol was produced from 100 g
      of cellulose supplied with 5 g l(-1) melibose within 60 h. The yield (g of
      ethanol produced/g of carbohydrate consumed) was 0.44 g/g, which corresponds to
      88.0% of the theoretical yield.

PMID- 22586920
TI  - [Development and optimization of immunoassays for the detection of botulinum
      toxins].
AB  - Monoparametric immunoassay tests for detecting botulinum toxins types A and B and
      multiparametric assays for simultaneous detection of botulinum toxins type A and
      B have been developed. It is shown that the sensitivity of assays is affected by
      the size of nanoparticles of colloidal gold used as a marker of antibodies, load
      intensity of antibodies of colloidal gold in conjugates, the type of analytical
      membranes, as well as the chemical composition of buffer solutions used for the
      storage of conjugates and immunoassay analysis. The detection limit of
      monoparametric immunoassay tests is 0.5 ng/ml; that of multiparametric assays,
      5.0 ng/ml. The developed immunoassay can be used for rapid assay of product
      quality, for grade control of botulinum toxins in pharmaceuticals, and
      environmental monitoring.

PMID- 22586921
TI  - [Comparison of nucleotide sequences of ribosomal DNA of the mosquito genera Aedes
      and Ochlerotatus (Diptera: Culicidae: Aedini)].
AB  - Morphological study allowed identifying 9 species of mosquitoes of the genus
      Ochlerotatus and 2 species of the genus Aedes. Sequencing of the rDNA region was
      performed for all these speciemens. The sequences of rDNA were the following: A.
      cinereus -868 bp, A. vexans--889 bp, Och. cantans--803 bp, O. excrucians--801 bp,
      O. euedes--794 bp, Och. cyprius--777 bp, O. diantaeus--758 bp, O. intrudens--817
      bp, Och. punctor--783 bp, O. dorsalis--748 bp, O. species--767 bp. On average,
      the size of Aedes rDNA fragments exceeds rDNA of Ochlerotatus by 90-100 bp. The
      sequences are characterized by a high number of insertions and deletions, and
      also by point substitutions of nucleotides. It is important to notice that
      interspecific differences include not only different regions of the internal
      transcribed spacers, but also the conservative site which is represented by the
      5.8S gene. Among four substitutions in this gene, one (C/A) represents the
      difference between Aedes and Ochlerotatus, the next (T/A) distinguishes A.
      cinereus from Ochlerotatus speciment and A. vexans, and two substitutions (A/C,
      T/G) testify the similarity between O. dorsalis and O. species and specimens of
      Aedes. Besides, two more deletions are typical for O. dorsalis and O. species.
      One deletion is com- mon, it distinguishes them from the other examined species,
      and another one is typical only for O. dorsalis. When analyzing morphological
      characteristics and comparing nucleotide rDNA sequences of O. species with the
      database, the similarity to O. caspius has been revealed. On the whole,
      phylogenetic relationships among Ochlerotatus species correspond to subdivision
      into groups based on morphological characters. Probably, examination of the
      larger number of specimens will change the morphological division into groups.

PMID- 22586922
TI  - [Variability of the dimensional structure in the hemipopulation of Thominx
      neopulchra (Nematoda: Capillariidae) females from bats of the genus myotis
      (Chiroptera: Vespertilionidae)].
AB  - Variability of the dimensional structure in the hemipopulation Thominx neopulchra
      females from 3 species of the genus Myotis bats in the Zhiguli State Reserve was
      examined. The size of T. neopulchra from different bat species varied within the
      limits constituting 10.17-13.41 mm. It was demonstrated that the variability of
      the dimensional structure in the subpopulation group T. neopulchra from
      Daubenton's bats did not depend on the number of parasites in the host and the
      season and is probably determined by the genetic polymorphism of the parasite
      population.

PMID- 22586923
TI  - [Morphology and taxonomy of two new cercariae of the group microcotylae].
AB  - Two new microcotylous cercariae are described. Their morphology is described and
      the differential diagnoses is given. All description are allustrated. For the
      first time, taxonomy of some microcotylous cercariae is discussed on the basis of
      their basic morphology.

PMID- 22586924
TI  - [A new nematode species, Physaloptera musayevi sp. n., from the Lybian jird
      Meriones libycus and the social vole Microtus socialis in the Gobustan area of
      Azerbaijan Republic].
AB  - Nematodes belonging to the genus Physaloptera Rudolphi, 1819 were obtained from
      the Lybian jird Meriones libycus and the social vole Microtus socialis in the
      Gobustan area as a result of helminthological research. These nematodes
      significantly differed from other species of the genus in morphological and
      morphometric characters. In the present paper, they are described as the new
      species Physaloptera musayevi sp. n.

PMID- 22586925
TI  - [A checklist of protozoan and metazoan parasites of the burbot (Lota lota)].
AB  - The parasite fauna of the burbot (Lota lota) within its natural range is
      reviewed. The sent paper summarizes the data on parasites of the burbot from
      water bodies of Eurasia and North America, based on published monographs,
      reviewed journals, scientific reports, conference contributions, and PhD theses.
      The checklist includes all protozoan and metazoan parasites of the burbot. A
      total of 242 parasite species/taxa were recorded in the burbot (Ki
      netoplastomonada--4, Parasitomonada--3, Coccidiomorpha--1. Microsporidea--3,
      Myxosporidia--35, Pleurostomata--1. Cyrtostomata--3, Peritricha--20. Protozoa
      incertae sedis--1. Monogenea--8, Cestoda--23, Digenea--50. Nematoda--36,
      Acanthocephala--28, Hirudinea--11. Bivalvia--5, Crustacea--10). Most parasites
      belong to digenean trematodes. Most of these species (183 species/taxa) were
      recorded on Eurasian and only 92--in North America fishes. Several parasite
      species recorded from the burbot are discussed in relation to host specificity
      and their geographical distribution.

PMID- 22586926
TI  - [The first international annual symposium on the control of parasitic diseases].

PMID- 22586927
TI  - [EEG correlates of geno-phenotypical features of the brain development in
      children of the native and newcomers' population of the Russian North-East].
AB  - Traditional and original methods of EEG analysis were used to study the brain
      electrical activity maturation in 156 children and adolescents from 7 to 17 years
      old who represented the native (Koryaks and Evenks) and newcomers' populations
      living in severe climatic and geographic conditions of the Russian North-East.
      New data revealing age-, sex- and ethnic-related features in quantitative EEG
      parameters are presented. Markers are obtained that characterize alterations in
      the structure of interaction between different EEG rhythms. The results
      demonstrate age-dependent transformation of this structure separated in time for
      both different cortical areas and different EEG frequency bands. These
      alterations show time lag from 2 to 3 years in children of native population
      compared to the newcomers. The revealed differences are assumed to reflect geno
      phenotypical features of morpho-functional CNS development in children of the
      native and newcomers' population that depend on strong adaptation tension for
      extreme environmental conditions.

PMID- 22586928
TI  - [Organisation of the hemisphere interaction in preschool children and in adults
      during mental speech production and speech perception].
AB  - The main goal of this study was to investigate reorganisation of the EEG systemic
      interactions spatial structure during mental speech production in preschool
      children: generating sentences from the set of words and generating words from
      the set of phonemes. In both cases, interhemisphere biopotential relations
      significantly increased as compared with the baseline (resting with closed eyes).
      Results of the EEG cross-correlation and coherent analyses showed that during
      verbal tasks marked intensification of hemisphere interaction was observed. High
      coefficients of statistic similarity between intercortical interactions patterns
      in adults and children during sentence and words generating were observed (SC =
      0.71 & 0.62 respectively). Opposite to that, lesser coefficients of statistic
      similarity were observed between these two groups during grammar and semantic
      mistakes identification (SC < or = 0.50). According to this data we could expect
      a relatively high maturation level of central mechanisms which underlie the
      processes of speech production rather than mechanisms which underlie grammar and
      semantic mistakes identification in preschool children.

PMID- 22586929
TI  - [Functional profiles typical of the male and female residents in different
      climatic-geographical areas of Magadan region].
AB  - Residents of the Extreme North, in total 255 males and 72 females were examined
      to study morpho-fuctional changes occurring in dependence on the area of
      residence. It was found that the subjects who recide in the towns of Magadan and
      Susuman demonstrated adaptive changes in somatometric parameters as well as in
      functioning of the body cardio-respiratory and gas-transporting systems that can
      be considered as a compensatory response providing the body energy balance and
      homeostasis maintenance at the level the unfavourable environmental factors.

PMID- 22586930
TI  - [Biorhythmic markers of stress and dysadaptation condition at work on a
      rotational basis in the north].
AB  - Within the limits of researches of medical and biologic problems of work on a
      rotational basis in regions with extreme climatic conditions, the concept of
      suboptimal strategy of adaptation as "incomplete adaptation" (IA) has been
      developed. A basic IA at work on a rotational basis makes synchronisation
      infringement of functions which develops at a change of time zones at cross
      meridian migrations, and as a result of occurrence of climatic stress at cross
      latitude migrations. The condition of IA is characterised by reactive anxiety,
      inversion of inter-hemisphere domination, infringement of circadian rhythms,
      boundary shifts of the hormonal status, the lowered physical and intellectual
      working capacity, features of psycho-somatic tiredness. In modelling experiments,
      it is shown that chronic infringement of circadian rhythms at IA has the
      expressed "acute" form which then later passes into the hidden form. In the phase
      of hidden form, functional reserves of the organism decrease and the risk of
      diseases increases.

PMID- 22586931
TI  - [Adaptation to military-professional work].
AB  - Theoretical and practical aspects of a problem of adaptation to military
      professional work are considered. Neurophysiological mechanisms of adaptation of
      military men to conditions of hot mountain-desert climate are revealed. Condition
      of the opioidergic system is shown at fighting stress, and its role in occurrence
      of illness of adaptation is described. Influence of extreme factors of a hot
      climate mountain-desert district is accompanied by infringement of
      interhemisphere mutual relations and psychosomatic changes.

PMID- 22586932
TI  - [The stress of mortally dangerous conditions: the individual psychophysiological
      mechanisms of adaptation in life-threatening situations].
AB  - Investigation into the mechanisms of the individual psychophysiological
      adaptation to life-threatening situations was performed. The data analysis of
      evoked potentials induced with verbal stimuli in 30-50-msec exposures was
      executed. Cross-correlation and wavelet analysis, as well as neurone algorithms
      were used to define total brain response to each stimulus and its duration.
      Correlation of the estimated parameters with subconscious aspects of psychic
      activity is discussed. Results of the studies performed with this neurosemantie
      method in various groups of subjects perceiving threat to life in the course of
      their performance, are presented. Described changes in the subconscious response
      mechanisms can help to clarify the direction for creation of new approaches with
      psychological correction and support.

PMID- 22586933
TI  - [The problem of estimation of the organism adaptable opportunities under
      stressful influences].
AB  - The human organism testing in conditions of modern scientific and technical
      progress constant stressful influences (industrial, social, psycho-emotional) was
      carried out for continuous adaptation to the environment: changing of the level
      of functioning of separate systems and a corresponding tension of regulatory
      mechanisms occurred. In the article, theoretical bases and methodology of
      studying the adaptable capacities of the organism are considered. The
      prenosological diagnostics was used for studying functional conditions on the
      verge of norm and pathology. The heart rate variability analysis was used based
      on mathematical model of functional conditions. Concrete technologies and results
      of evaluation of the adaptation capacities of the organism in space and aviation
      medicine are presented as well as in applied physiology.

PMID- 22586934
TI  - [Molecular-cellular and hormonal mechanisms of induced brain tolerance of extreme
      factors].
AB  - This review includes results of own studies and literature data on the topical
      problem of neurobiology and medicine: discovery of the mechanisms of increased
      brain resistance to extreme exposures. The emphasis is made on the molecular
      cellular and hormonal mechanisms of hypoxic preconditioning-induced brain
      tolerance to injurious hypoxia, psychoemotional and traumatic stress. A role of
      basic hormonal and intracellular cascade pro-adaptive processes mediating the
      neuroprotective action of hypoxic preconditioning is reviewed. A dynamics of the
      mechanisms of development of induced susceptible brain areas (hippocampus,
      neocortex) tolerance which includes phases of induction, transformation and
      expression, is presented. New data on preconditioning-induced cross-tolerance
      providing increased brain resistance not only to hypoxia but also to other
      stresses are reported. For the first time neuroprotective effects of hypoxic
      postconditioning are described.

PMID- 22586935
TI  - [Systemic and organ mechanisms of the organism oxygen supply in high altitude].
AB  - Organ and systemic mechanisms of organism oxygen supply in adaptation to high
      altitude of the Tien Shan (3200 m above sea level) were studied in the
      experiments on dogs. It is shown that in the first few days in the mountains (5
      7th and 15th days) oxygen supply of the body is due to the increased delivery of
      O2 to organs and tissues; in the process of adaptation (30 days), the efficiency
      of tissue utilization of O2 increases. Changes of organ blood flow in visceral
      and somatic organs, features of compensation of the tissue hypoxia and oxygen
      supply of the heart, brain, skeletal muscle in different periods of adaptation to
      high altitude were established.

PMID- 22586936
TI  - [Phospholipids and structural modification of tissues and cell membranes for
      adaptation in high altitude mountains].
AB  - The nature of the impact of physical factors of high altitudes (3200 m) on the
      lipids of tissues and membranes of animals was researched. It was established
      that the adaptation process in Wistar rats was followed by peroxide degradation
      and subsequent modification of the phospholipids' structure of tissues and
      microsomal membranes. Adaptive phospholipids reconstruction takes place in
      microsomal membranes in the tissues of the lungs, brain, liver and skeletal
      muscles. Together with this, the amount of phosphatidylinositol and phosphatidic
      acid accumulates, indicating that the hydrolysis of phosphatidylinositol-4, 5
      biphosphate to diacylglycerol and secondary messenger--inositol triphosphate,
      occurs. A decrease in temperature adaptation (+10 degrees C) leads to a more
      noticeable shift in peroxide oxidation of lipids, phospholipid structure in the
      tissues and membranes rather than adaptation in thermoneutral conditions (+30
      degrees C). Modification of lipid composition of tissues and cell membranes in
      the highlands obviously increases the adaptive capabilities of cells of the whole
      body: physical performance and resistance to hypoxia increases in animals.

PMID- 22586937
TI  - [Nitric oxide metabolites level in human serum in acute normobaric hypoxia].
AB  - The influence of acute normobaric hypoxia on NO metabolites level of the blood
      serum in volunteers at respiration of hypoxic gas mixture containing 8 % of O2
      during 25 min was investigated. Health status of participants and the hypoxia
      intensity were monitored with a complex of indexes: EEC, ECG, blood pressure,
      oxygen saturation of haemoglobin, cardiac output, gas composition of exhaled air.
      Cluster analysis (k-means clustering) conducted among volunteers that have
      successfully passed the test has shown presence of two groups differing in NO
      metabolites level during experiment. Statistically significant differences on NO
      metabolites level between groups were observed before hypoxia exposure, on 10th
      minute of acute hypoxia (maximum difference) and on 5th minute of recovery.
      Differences on NO metabolites level between groups have been caused by changes in
      nitrates concentration whereas nitrites level did not differ. The least NO and
      nitrates levels have been revealed in volunteers that have been in volunteers
      that had interrupted performance of the test after 10 minutes of respiration of
      hypoxic gas mixture. Thus the moderate increase of NO metabolites level due to
      accumulation of nitrates at acute hypoxia testifies to good adaptive reserves of
      system of nitric oxide generation in organism.

PMID- 22586938
TI  - [Low-frequency neuronal oscillations as operant processing of integrative
      mechanisms of conditioning and plasticity].
AB  - It was found that neuronal activity of the rabbit somatosensory cortex could be
      operantly conditioned according to the given algorithm of biofeedback control of
      nociceptive stimulation leading to rising or lowering of firing rate of multiunit
      activity, or to changes of range of units interspike intervals, or neuronal
      firing patterns for conditional stimulus, which become operants. Neuronal
      interactions of its population with feedback and systems of cardiovascular and
      pain regulation lead to appearance of wave patterns, combining elements to
      integrative activity by conditioning. Low-frequency oscillations of neuronal
      assemblies within range of 0.02-0.8 Hz act as operant processing in mechanisms of
      system plasticity and conditioning.

PMID- 22586939
TI  - [Understanding a new conception of addiction in current clinical practices].
AB  - This paper described the historical process that the conception of "addiction"
      and "dependence" have been formed and changed. Before, the "addiction" was a
      prejudiced word used when people contempt an individual with compulsive drinking
      or taking psychoactive drugs, and this word implied moralistic and ethical faults
      of the individual. After that, this word describing an individual without control
      of drinking was taken place by the "dependence." This is the neutral and medical
      conception, defined by presence of tolerance and withdrawal symptoms, although it
      was based on the "alcoholism." which originated in the citizen movement in 1930s
      in U.S. Recently some professionals have preferred to use the "addiction" when
      describing an individual losing control of deviated, impulsive, and repetitive
      behavior including pathological gambling and compulsive buying. These behaviors
      have been discriminated form substance dependence, while clinically applied to
      analogical treatment to substance dependence. However, the DSM-5 draft which the
      American Psychiatric Association has published as a draft of new diagnostic
      criteria for mental disorders has classified both of substance dependence and
      addictive behavior into the same category, and has removed the word "dependence"
      in the description. In this paper, we looked back on historical conflicts between
      the two words of "dependence" and "addiction," and discussed the clinical
      meanings and problems of these words.

PMID- 22586940
TI  - [Study on risk factors of suicidal ideation in people with drug abuse].
AB  - In Japan, the target mental disorders of preventive strategies for suicide had
      been limited to be mood disorder, but recently drug abuse are known to be
      significant as a cause of suicide because some researches has found the
      association between substance use disorder and suicidal behavior in Japan.
      However, the preventive plans for suicide of drug abusers has not been developed
      yet. In this study we would like to examine the risk factors of suicide ideation
      in Japanese drug abusers. We analyzed the data of 445 drug addicts from the
      Nationwide Research of Drug Addiction Rehabilitation Centers by Tokyo DARC and
      compared many variables including demographic factors, drug use status, family
      history, psychopathologies, treatment and daily life satisfactions between people
      with suicide ideations and without ideations. It was found that 182 cases (43.8%)
      had suicide ideations in a recent month, and that addicts who had suicide
      ideations had significantly shorter abstinence time, higher prevalence of
      victimized experiences before 15 years age, and more mental symptoms such as
      insomnia, depression, and psychotic symptoms, and more tendencies to use
      prescribed psychotropic drug than those without suicide ideation. These results
      suggested that to prevent suicide of drug abusers, we should pay attention to
      family histories, insomnia and abstinence periods, and help them recovery from
      psychological damages caused by childhood trauma without inappropriate
      medications.

PMID- 22586941
TI  - Genetic dissection of pulmonary tuberculosis: implications for drug and vaccine
      development.

PMID- 22586942
TI  - [Pathology specimens suggest a history of Hansen's disease].

PMID- 22586943
TI  - [For the future of Japanese leprosy association (3)].

PMID- 22586944
TI  - [Discussion on the original theory of "care"--the common ground and essence of
      nursing and social welfare].

PMID- 22586945
TI  - [Stress management: how to cope with stress].

PMID- 22586946
TI  - Report on research approach to diabetic foot syndrome in Japan.

PMID- 22586947
TI  - [Conjugal leprosy infection in Japan--case report and review].
AB  - The authors reported a conjugal leprosy infection observed in Japan. The husband,
      index case, first noticed sensory disturbance at the lower right leg in his
      forties. He developed edematous swelling with redness of the right hand and
      forearm at the age of 72 (1989), and then developed multiple erythema and
      hypesthesia at the extremities. He was diagnosed as BL type leprosy (reactional
      stage) and treated with multi-drug therapy. His 71-year-old wife developed a few
      erythema at the right forearm in 1993. She was classified as BT type. The
      duration of their marriage life was over forty years. The couple did not have
      consanguinity. No other leprosy patients were found in their lineage. From their
      clinical courses the authors concluded that the husband infected his wife.
      According to Japanese literatures, the frequency of conjugal leprosy among new
      patients in Japan was approximately 1%. There were worldwide observations that
      the husband often infected the wife, and mostly the index case was multibacillary
      and the secondary case paucibacillary. The authors reviewed definition and
      frequency of conjugal leprosy, factors in conjugal infection and leprosy
      infection among the adults.

PMID- 22586948
TI  - [Present leprosy situation in the world in 2011].
AB  - The epidemiological situation of leprosy is reported by the health division of
      each country to WHO. The reported data is collected by WHO and is immediately run
      on the Weekly Epidemiological Record. On this latest edition, data from the
      beginning of 2010 was reported. The Enhanced global strategy for further reducing
      the disease burden due to leprosy (plan period: 2011-2015) emphasizes reducing
      grade-2 disabilities among new cases. The burden of leprosy continues to decline
      globally as a result of sustained efforts carried out by national leprosy
      programmes along with continued support from both national and international
      partners. Improving the management of complications through the development of an
      effective referral service and increased community awareness about the disease
      will ensure that cases present for diagnosis at an early stage and will help
      reduce the disease burden further.

PMID- 22586949
TI  - [Ghana: the experience in the land highly endemic for Buruli ulcer].

PMID- 22586950
TI  - [Characteristics of soil respiration components and their temperature sensitivity
      in a Pleioblastus amarus plantation in rainy area of West China].
AB  - To understand the characteristics of soil respiration components and their
      temperature sensitivity in a Pleioblastus amarus plantation in the Rainy Area of
      West China, a one-year periodic monitoring was conducted in a fixed plot of the
      plantation from February 2010 to January 2011. In the plantation, the mean annual
      soil respiration rate was 1.13 micromol x m(-2) x s(-1), and the soil respiration
      presented a clear seasonal pattern, with the maximum rate in mid-summer and the
      minimum rate in late winter. The contribution rates of the respiration of litter
      layer, root-free soil, and root to the total soil respiration of the plantation
      accounted for 30.9%, 20.8% and 48.3%, respectively, and the respiration of the
      components had a similar seasonal pattern to the total soil respiration, being
      related to temperature and litterfall. The annual CO2 efflux from the total soil
      respiration, litter layer CO2 release, root-free soil CO2 release, and root
      respiration was 4.27, 1.32, 0.87 and 2.08 Mg C x hm(-2) x a(-1), respectively.
      The total soil respiration and its components had significant positive linear
      correlations with litterfall, and significant positive exponential correlations
      with air temperature and the soil temperature at depth 10 cm. The Q10 values of
      total soil respiration, litter layer CO2 release, root-free soil CO2 release, and
      root respiration calculated based on the soil temperature were 2.90, 2.28, 3.09
      and 3.19, respectively, suggesting that the temperature sensitivity of litter
      layer CO2 release was significantly lower than that of the total soil respiration
      and of its other components.

PMID- 22586951
TI  - [Contribution of soil fauna to the mass loss of Betula albosinensis leaf litter
      at early decomposition stage of subalpine forest litter in western Sichuan].
AB  - In order to quantify the contribution of soil fauna to the decomposition of birch
      (Betula albosinensis) leaf litter in subalpine forests in western Sichuan of
      Southwest China during freeze-thaw season, a field experiment with different mesh
      sizes (0.02, 0.125, 1 and 3 mm) of litterbags was conducted in a representative
      birch-fir (Abies faxoniana) forest to investigate the mass loss rate of the birch
      leaf litter from 26 October, 2010 to 18 April, 2011, and the contributions of
      micro-, meso- and macro-fauna to the decomposition of the leaf litter. Over the
      freeze-thaw season, 11.8%, 13.2%, 15.4% and 19.5% of the mass loss were detected
      in the litterbags with 0.02, 0. 125, 1 and 3 mm mesh sizes, respectively. The
      total contribution of soil fauna to the litter decomposition accounted for 39.5%
      of the mass loss, and the taxa and individual relative density of the soil fauna
      in the litterbags had the similar variation trend with that of the mass loss
      rate. The contribution rate of soil fauna to the leaf litter mass loss showed the
      order of micro- < meso- < macro-fauna, with the highest contribution of micro
      fauna (7.9%), meso-fauna (11.9%), and macro-fauna (22.7%) at the onset of
      freezing stage, deeply frozen stage, and thawing stage, respectively. The results
      demonstrated that soil fauna played an important role in the litter decomposition
      in subalpine forests of western Sichuan during freeze-thaw season.

PMID- 22586952
TI  - [Characteristics of terrestrial ecosystem primary productivity in East Asia based
      on remote sensing and process-based model].
AB  - Based on the bi-linearly interpolated meteorological reanalysis data from
      National Centers for Environmental Prediction, USA and by using the leaf area
      index data derived from the GIMMS NDVI to run the process-based Boreal Ecosystems
      Productivity Simulator (BEPS) model, this paper simulated and analyzed the
      spatiotemporal characteristics of the terrestrial ecosystem gross primary
      productivity (GPP) and net primary productivity (NPP) in East Asia in 2000-2005.
      Before regional simulating and calculating, the observation GPP data of different
      terrestrial ecosystem in 15 experimental stations of AsiaFlux network and the
      inventory measurements of NPP at 1300 sampling sites were applied to validate the
      BEPS GPP and NPP. The results showed that BEPS could well simulate the changes in
      GPP and NPP of different terrestrial ecosystems, with the R2 ranging from 0.86 to
      0.99 and the root mean square error (RMSE) from 0.2 to 1.2 g C x m(-2) x d(-1).
      The simulated values by BEPS could explain 78% of the changes in annual NPP, and
      the RMSE was 118 g C x m(-2) x a(-1). In 2000-2005, the averaged total GPP and
      total NPP of the terrestrial ecosystems in East Asia were 21.7 and 10.5 Pg C x a(
      1), respectively, and the GPP and NPP exhibited similar spatial and temporal
      variation patterns. During the six years, the total NPP of the terrestrial
      ecosystems varied from 10.2 to 10.7 Pg C x a(-1), with a coefficient of variation
      being 2. 2%. High NPP (above 1000 g C x m(-2) x a(-1)) occurred in the southeast
      island countries, while low NPP (below 30 g C x m(-2) x a(-1)) occurred in the
      desert area of Northwest China. The spatial patterns of NPP were mainly
      attributed to the differences in the climatic variables across East Asia. The NPP
      per capita also varied greatly among different countries, which was the highest
      (70217 kg C x a(-1)) in Mongolia, far higher than that (1921 kg C x a(-1)) in
      China, and the lowest (757 kg C x a(-1)) in India.

PMID- 22586953
TI  - [Evaluation of remote sensing extraction methods for vegetation phenology based
      on flux tower net ecosystem carbon exchange data].
AB  - Taking the vegetation phenological metrics derived from the net ecosystem carbon
      exchange (NEE) data of 72 flux towers in North America as the references, a
      comprehensive evaluation was conducted on the three typical classes of remote
      sensing extraction methods (threshold method, moving average method, and function
      fitting method) for vegetation phenology from the aspects of feasibility and
      accuracy. The results showed that the local midpoint threshold method had the
      highest feasibility and accuracy for extracting vegetation phenology, followed by
      the first derivative method based on fitted Logistic function. The feasibility
      and accuracy of moving average method were determined by the moving window size.
      As for the MODJS 16 d composited time-series normalized difference vegetation
      index (NDVI), the moving average method had preferable performance when the
      window size was set as 15. The global threshold method performed quite poor in
      the feasibility and accuracy. Though the values of the phenological metrics
      extracted by the curvature change rate method based on fitted Logistic function
      and the corresponding ones derived from NEE data had greater differences, there
      existed a strong correlation between them, indicating that the vegetation
      phenological metrics extracted by the curvature change rate method could reflect
      the real temporal and spatial variations of vegetation phenology.

PMID- 22586954
TI  - [Effects of elevated CO2 on forest soil CH4 consumption in Changbai Mountains].
AB  - Elevated atmospheric CO2 concentration may affect the oxidation rate of methane
      (CH4 ) in forest soil. In this study, the effects of a 6-year exposure to
      elevated CO2 concentration (500 micromol x mol(-1)) on the soil microbial process
      of CH4 oxidation under Quercus mongolica seedlings were investigated with open
      top chamber (OTC), and specific 16S rRNA and pmoA gene fragment primers were
      adopted to analyze the diversity and abundance of soil methanotrophs. Comparing
      with that under ambient CO2 and open-air, the soil methane consumption under
      elevated atmospheric CO2 during growth season was reduced by 4% and 22%,
      respectively. The specific 16S rRNA PCR-DGGE analysis showed that under elevated
      CO2, the community structure of methane-oxidizing bacteria (MOB) changed, and the
      diversity index decreased. Elevated CO2 concentration had no distinct effects on
      the abundance of Type I MOB, but decreased the amount of Type II MOB
      significantly. The pmoA gene copy number under elevated CO2 concentration
      decreased by 15% and 46%, respectively, as compared with that under ambient CO2
      and open-air. Our results suggested that elevated atmospheric CO2 decreased the
      abundance and activity of soil methanotrophs, and the main cause could be the
      increase of soil moisture content.

PMID- 22586955
TI  - [Characteristics of carbon storage and sequestration in different age beech
      (Castanopsis hystrix) plantations in south subtropical area of China].
AB  - To transform large area pure conifer plantations by planting indigenous and
      valuable broad-leaved tree species has been advocated as an effective close-to
      nature forest management in sub-tropical China. Taking the 10-, 20- and 27-year
      old Castanopsis hystrix plantations in Guangxi of South China as test objects and
      by the methods of plot investigation and biomass measurement, this paper studied
      the carbon content in different plant organs, litter layers, and soil layers and
      the carbon storage and its allocation in tree layer, litter layer and soil layer.
      For the test plantations, the carbon content in different C. hystrix organs
      ranged from 49.7% to 57.9%, and that in litter layer was 40.8%-50.5%, being
      higher in fresh litter layer than in semi-decomposed litter layer. The carbon
      storage in the soil profiles (0-60 cm) increased with plantation age but
      decreased with soil depth. The total carbon storage in the 10-, 20- and 27-year
      old plantations was 182. 42, 234.75 and 269. 75 t x hm(-2), respectively, among
      which, tree layer, litter layer and soil layer occupied 19.8%, 32.0% and 32.8%,
      1.5%, 1.6% and 1.3%, and 78.7%, 66.4% and 65.9%, respectively. The annual net
      carbon sequestration of the 10-, 20- and 27-year-old plantations was 4.70, 5.64
      and 5.18 t x hm(-2), respectively. It was considered that C. hystrix had a high
      capability in carbon sequestration, being able to be an ideal tree species for
      multi-purpose forest management with large and valuable timber production.

PMID- 22586956
TI  - [Forest carbon rates at different scales in Northeast China forest area].
AB  - To accurately estimate forest carbon storage is of significance in researching
      terrestrial ecosystem carbon cycle and global change. Based on the survey data
      from the representative plots in Northeast China forest area (Da Xing' an
      Mountains, Xiao Xing' an Mountains, Zhangguangcai Mountains and Changbai
      Mountains) in 2007 and 2008 and the inventory data in the same period, and by
      using the models for estimating ground tree biomass, shrub biomass, and grass
      biomass and the Multi N/C 3000 for measuring forest carbon rate in laboratory,
      this paper calculated the forest biomass and carbon storage in the forest area,
      and analyzed the variation and stability of the forest carbon rates at different
      scales. There was an obvious difference in the carbon rates among tree organs,
      being the highest in leaf (0.4448), followed by in branch (0.4422), bark
      (0.4398), and trunk (0.4351). In Changbai and Zhangguangcai Mountains, coniferous
      forest had a higher carbon rate than broad-leaved forest; whereas in Daxing' an
      and Xiaoxing' an mountains, it was in adverse. In Northeast China forest area,
      the forest carbon rates were relatively stable, with a total value of 0.44.

PMID- 22586957
TI  - [Vegetation succession on retired croplands during their recovery processes in
      Dan-Han River Watershed of Shaanxi Province, Northwest China].
AB  - Taking naturally recovering plant communities on the croplands having been
      retired for different years and distributed on the southern and northern slopes
      in the Dan-Han River watershed of Shaanxi Province as test objects, an
      investigation was conducted on their community species composition, diversity
      characteristics, and community polar ordination. In the study area, the
      vegetation succession process on the retired croplands followed the stages of
      annual herb community-->perennial herb community-->shrub-herb community-->arbor
      shrub-herb community. The formation period for perennial herb community, shrub
      herb community, and arbor-shrub-herb community was about 2-5 a, 7-10 a, and more
      than 30 a respectively. On the southern and northern slopes, dif ferent types of
      retired croplands had the same vegetation succession stages, and had small
      discrepancies in species diversity indices. With increasing retired years, the
      species diversity indices on the southern slope increased after an initial
      decrease, while those on the northern slope had a fluctuated increase first, and
      slightly decreased by the end of the 30 a.

PMID- 22586958
TI  - [Effects of shading on two Sphagnum species growth and their interactions].
AB  - Taking Sphagnum palustre and S. fallax as test materials, this paper studied
      their growth and interactions under shading. In monoculture, shading promoted the
      height growth of S. palustre markedly, but had no effect on the growth of S.
      fallax and the biomass and branching of S. palustre. In mixed culture, S. fallax
      suppressed the increase of biomass and branching of S. palustre, while S.
      palustre had no effects on S. fallax. With the increase of shading stress, the
      competition of neighbour on S. fallax intensified. When the stress increased
      further, neighbor effect on S. fallax tended to be positive. However, the effect
      of neighbour on S. palustre was always competitive and did not change with the
      increase of shading stress.

PMID- 22586959
TI  - [Effects of desulfurization waste on calcium distribution, Ca(2+)-ATPase
      activity, and antioxidant characteristics of rice leaf under alkali stress].
AB  - To approach the action mechanisms of desulfurization waste on alleviating alkali
      stress-induced injury of rice, a pot experiment was conducted to study the
      variations of leaf total calcium content, calcium distribution, plasma membrane
      Ca(2+)-ATPase activity, and reactive oxygen content of rice seedlings under
      alkali stress after the application of desulfurization waste. In the control, a
      few calcium particulates scattered in the cell wall and chloroplasts, while
      applying desulfurization waste or CaSO4 increased the calcium particulates in the
      plasma membrane, intercellular space, cell wall, and vacuole significantly. With
      the increasing application rate of desulfurization waste or CaSO4, the leaf total
      calcium content increased, Ca(2+)-ATPase activity in plasma membrane and
      tonoplast presented an increasing trend, plasma membrane relative permeability,
      MDA content, and O2 production rate decreased, and SOD and POD activities
      increased. The desulfurization waste could relieve the alkali stress to rice in
      some extent, and the main reactive compound in the waste could be CaSO4.

PMID- 22586960
TI  - [Effects of soil moisture before sowing and nitrogen fertilization on winter
      wheat yield and water use on Weibei Plain of Loess Plateau].
AB  - A five-year site-specific experiment was carried out on the Weibei Plain of Loess
      Plateau in Shaanxi Province of northwestern China to study the effects of soil
      moisture regime before sowing (SMBS) and nitrogen fertilization on the grain
      yield and water use of winter wheat. On the basis of applying 100 kg x hm(-2) of
      P2O5, five nitrogen fertilization levels (0, 80, 160, 240, and 320 kg N x hm(-2))
      were installed, and took the precipitation in the five years into consideration.
      In the study area, there was a linear correlation between the precipitation in
      summer (from July to September) and the SMBS, with an increment of 0.6 mm SMBS
      per 1 mm precipitation. For a stable or high wheat yield, the SMBS should be kept
      around 550 mm, and the precipitation in summer should be around 370-390 mm. In
      the years with adequate precipitation (> 386 mm) in summer, the SMBS in present
      winter wheat growth season less decreased by the increase of the nitrogen
      fertilization rate in previous growth season. However, in the years with less
      precipitation in summer (< 350 mm), the SMBS in present winter wheat growth
      season decreased significantly by 9-17 mm when the nitrogen fertilization rate in
      previous growth season was increased by each 100 kg N x hm(-2). In addition to
      SMBS, adequate precipitation in key growth stages was another important factor to
      ensure the wheat yield in dryland area because 1 mm SMBS could produce 10.6-11.4
      kg x hm(-2) of wheat grain, and 1 mm precipitation occurred in the key growth
      stages could lead to more grain yield as high as 30.6-33.1 kg x hm(-2). Variation
      analysis showed that nitrogen fertilization rate affected the utilization degree
      of SMBS by winter wheat, while SMBS controlled the allocation and transportation
      of dry matter from vegetative parts to grain.

PMID- 22586961
TI  - [Environmental effects of applying heavy metal-containing municipal sewage sludge
      on wheat-rice rotation system on different types of soil].
AB  - A pot experiment with the yellow soil and limestone soil from Guizhou province,
      and paddy soil from Zhejiang Province was conducted to study the impacts of
      applying municipal sewage sludge containing different concentrations of heavy
      metals on the wheat and rice growth and their Zn and Cd absorption. The risks of
      the crop heavy metals pollution caused by the application of the same sludge
      differed with tested soils. On the yellow soil and paddy soil, applying the
      sludge containing high concentration heavy metals induced higher pollution risks
      to the crops. Applying the sludge 1.6% in dry mass and containing 1789 mg x kg(
      1) of Zn and 8.47 mg x kg(-1) of Cd to yellow soil made the Zn and Cd
      concentrations in wheat grains reached 109 and 0.08 mg x kg(-1), and after the
      second time application of the same dosage of this sludge after rice planting,
      the Zn and Cd concentrations in brown rice reached 52.0 and 0.54 mg x kg(-1),
      respectively. However, applying the sludge to calcareous soil had no pollution
      risk to the edible parts of wheat and rice. Soil NH4OAc-extractable Zn was the
      main factor affecting the Zn concentration in wheat grain and brown rice, but
      soil NH4OAc-extractable Cd had less effect on the Cd concentration in wheat grain
      and brown nce. Applying the sludge containing high concentration Zn and Cd to the
      three soils made the concentrations of total Zn and Cd in the soils increased
      significantly, and after the first time and the second time of the application,
      the total Zn concentration in the soils all exceeded the 2nd level of the
      national soil environmental quality standards.

PMID- 22586962
TI  - [Effects of organic amendments on the growth and heavy metal uptake of rice on a
      contaminated soil].
AB  - A pot experiment was carried out to investigate the effects of three organic
      amendments (organic carbon material, rapeseed cake, and pig manure) on the growth
      and heavy metal uptake of rice on a heavy metal mixed contaminated paddy soil.
      Applying rapeseed cake and pig manure could mitigate the toxic effect of heavy
      metals on rice plant. The two organic amendments increased the shoot biomass and
      grain yield significantly, and decreased the heavy metal concentration in brown
      rice. Under the application of organic carbon material, rice growth was
      inhibited. As compared with the control, applying rapeseed cake and pig manure
      increased the grain yield by 128.3% and 67.9%, and decreased the Cd, Cu, and Zn
      concentrations in brown rice by 47.6%, 35.2% and 21.5%, and 9.5%, 21.2% and 9.3%,
      respectively. The shoot biomass and its total accumulation of Cd, Cu, and Zn had
      significant negative correlations with the soil DTPA-extractable heavy metals.

PMID- 22586963
TI  - [Effects of tilage mode and deficit irrigation on the yield and water use of
      transplanted cotton following wheat harvest under sprinkler irrigation].
AB  - To develop a suitable tillage mode and irrigation schedule of transplanted cotton
      following wheat harvest under sprinkler irrigation, a field experiment was
      conducted to study the effects of different tillage modes (conventional tillage
      and no-tillage) and different irrigation schedules (45 and 22.5 mm of irrigating
      water quota) on the water consumption, seed yield, water use efficiency, and
      fiber quality of cotton. Comparing with conventional tillage, no-tillage
      decreased the soil evaporation among cotton plants by 20.3%. Whether with
      conventional tillage or with no-tillage, deficit irrigation (22.5 mm of
      irrigating water quota) did not affect seed yield and fiber quality, while
      decreased the water consumption and improved the water use efficiency. No-tillage
      with 22.5 mm of irrigating water quota under sprinkler irrigation not only
      decreased the soil evaporation effectively, but also achieved water-saving, high
      quality and high yield of transplanted cotton following wheat harvest.

PMID- 22586964
TI  - [Effects of water storage in deeper soil layers on the root growth, root
      distribution and economic yield of cotton in arid area with drip irrigation under
      mulch].
AB  - Taking cotton cultivar Xinluzao 13 as test material, a soil column culture
      expenment was conducted to study the effects of water storage in deeper (> 60 cm)
      soil layer on the root growth and its relations with the aboveground growth of
      the cultivar in arid area with drip irrigation under mulch. Two levels of water
      storage in 60-120 cm soil layer were installed, i. e., well-watered and no
      watering, and for each, the moisture content in 0-40 cm soil layer during growth
      period was controlled at two levels, i.e., 70% and 55% of field capacity. It was
      observed that the total root mass density of the cultivar and its root length
      density and root activity in 40-120 cm soil layer had significant positive
      correlations with the aboveground dry mass. When the moisture content in 0-40 cm
      soil layer during growth season was controlled at 70% of field capacity, the
      total root mass density under well-watered and no watering had less difference,
      but the root length density and root activity in 40-120 cm soil layer under well
      watered condition increased, which enhanced the water consumption in deeper soil
      layer, increased the aboveground dry mass, and finally, led to an increased
      economic yield and higher water use efficiency. When the moisture content in 0-40
      cm soil layer during growth season was controlled at 55% of field capacity and
      the deeper soil layer was well-watered, the root/shoot ratio and root length
      density in 40-120 cm soil layer and the root activity in 80-120 cm soil layer
      were higher, the water consumption in deeper soil layer increased, but it was
      still failed to adequately compensate for the negative effects of water deficit
      during growth season on the impaired growth of roots and aboveground parts,
      leading to a significant decrease in the economic yield, as compared with that at
      70% of field capacity. Overall, sufficient water storage in deeper soil layer and
      a sustained soil moisture level of 65% -75% of field capacity during growth
      period could promote the downward growth of cotton roots, which was essential for
      achieving water-saving and high-yielding cultivation of cotton with drip
      irrigation under mulch.

PMID- 22586965
TI  - [Effects of nitrogen fertilization rate and planting density on cotton boll
      biomass and nitrogen accumulation in extremely early maturing cotton region of
      Northeast China].
AB  - Taking cotton cultivars Liaomian 19 and NuCoTN 33B as test materials, a field
      experiment was conducted to study the effects of nitrogen fertilization rate (0,
      240 and 480 kg x hm(-2)) and planting density (75000, 97500 and 120000 plants x
      hm(-2)) on the boll biomass and nitrogen accumulation in the extremely early
      maturing cotton region of Northeast China. With the growth and development of
      cotton, the biomass and nitrogen accumulation of cotton boll, cotton seed, and
      cotton fiber varied in 'S' shape. Both nitrogen fertilization rate and planting
      density had significant effects on the dynamic characteristics of boll biomass
      and nitrogen accumulation, and on the fiber yield and quality. In treatment 240
      kg x hm(-2) and 97500 plants x hm(-2), the biomass of single boll, cotton seed
      and cotton fiber was the maximum, the starting time and ending time of the rapid
      accumulation period of the biomass and nitrogen were earlier but the duration of
      the accumulation was shorter, the rapid accumulation speed of the biomass was the
      maximum, and the distribution indices of the biomass and nitrogen were the lowest
      in boll shell but the highest in cotton seed and cotton fiber.

PMID- 22586966
TI  - [Effects of applying selenium on selenium allocation, grain yield, and grain
      quality of two maize cultivars].
AB  - A pot experiment with conventional maize cultivar ZD958 and glutinous maize
      cultivar JN218 was conducted to study the effects of applying different
      concentrations (0, 10, 25 and 50 mg x kg(-1)) of selenium (Se) on the Se
      allocation in plant organs, grain yield, and its quality. At low concentrations
      (< or = 10 mg x kg(-1)), Se stimulated maize growth, and increased biomass
      accumulation and grain yield significantly. At high concentrations (> 25 mg x kg(
      1)), Se inhibited maize growth, and decreased dry mass accumulation, grain yield,
      and its quality. The Se concentration in plant organs was in the order of root >
      leaf > stalk > sheath. The Se concentrations in plant organs had a positive
      correlation with the Se concentration in soil. Comparing with ZD958, JN218 could
      accumulate more Se in natural low-Se environment, but enrich lesser Se in the
      environment with 10 mg x kg(-1) of Se. Taking the Se accumulation amount in grain
      and aboveground vegetative organs as the standard for evaluation, JN218 was more
      available planted on natural low-Se (0.25 mg x kg(-1)) soil or high-Se (25 mg x
      kg(-1)) soil, while ZD958 was appropriate planted on Se-rich (10 mg x kg(-1))
      soil or Se-polluted (50 mg x kg(-1)) soil.

PMID- 22586967
TI  - [Effects of organic fertilizer application rate on leaf photosynthetic
      characteristics and grain yield of dryland maize].
AB  - A 4-year field experiment was conducted at the Heyang Research Station in Weibei
      dryland to study the effects of organic fertilizer application rate on the leaf
      photosynthetic characteristics and grain yield of dryland maize. Comparing with
      applying chemical fertilizer, applying organic fertilizer increased the leaf
      photosynthetic rate and stomatal conductance, but decreased the leaf
      intercellular CO2 concentration at each growth stage of maize significantly. With
      the increasing application rate of organic fertilizer, the leaf photosynthetic
      rate and stomatal conductance at each growth stage of maize had a gradual
      increase, while the leaf intercellular CO2 concentration had a gradual decrease.
      The leaf photosynthesis of maize at each growth stage was controlled by non
      stomatal factors, and the application of organic fertilizer reduced the non
      stomatal limitation on the photosynthesis performance significantly. The 4-year
      application of organic fertilizer improved soil nutrient status, and soil
      nutrients were no longer the main factors limiting the leaf photosynthetic rate
      and grain yield of maize.

PMID- 22586968
TI  - [Climatic suitability of single cropping rice planting region in China].
AB  - To clarify the leading climate factors affecting the distribution of single
      cropping rice planting region in China at national and annual temporal scales and
      to reveal the potential distribution and climatic suitability divisions of this
      planting region in China could not only provide scientific basis for optimizing
      the allocation of single cropping rice production, modifying planting pattern,
      and introducing fine varieties, but also ensure the food security of China. In
      this paper, the potential climate factors affecting the single cropping rice
      distribution in China at regional and annual scales were selected from related
      literatures, and the single cropping rice geographic information from the
      national agro-meteorological observation stations of China Meteorological
      Administration (CMA), together with the maximum entropy model (MaxEnt) and
      spatial analyst function of Arc-GIS software, were adopted to clarify the leading
      climate factors affecting the potential distribution of single cropping rice
      planting region in China, and to construct a model about the relationships
      between the potential distribution of the planting region and the climate. The
      results showed that annual precipitation, moisture index, and days of not less
      than 18 degrees C stably were the leading climate factors affecting the potential
      distribution of single cropping rice planting region in China, with their
      cumulative contribution rate reached 94.5% of all candidate climate factors. The
      model constructed in this paper could well simulate the potential distribution of
      single cropping rice planting region in China. According to the appearance
      frequency, the low, medium and high climatic suitability divisions of single
      cropping rice planting region in China were clarified, and the climate
      characteristics of the planting region in each climatic suitability division were
      analyzed.

PMID- 22586969
TI  - [Variations of microbial biomass and hydrolase activities in purple soil under
      different cropping modes as affected by ginger planting].
AB  - This paper studied the variations of soil microbial biomass C, N, and P contents
      and soil hydrolase activities under different cropping modes, i.e., corn + sweet
      potato intercropping (CS), soybean mono-cropping (SM), continuous cropping of
      ginger (CG), and rice-milk vetch rotation (RM) , after ginger planting in the
      purple soil area at the lower reaches of Minjiang River. Ginger planting
      decreased the soil microbial biomass C, N and P contents significantly. The
      decrement of the soil microbial biomass C and N contents after ginger planting
      was lesser under CS and RM than under SM and CG, but the soil microbial biomass P
      content was in adverse. Ginger planting also decreased the soil acid phosphatase
      activity significantly, and the decrement was the greatest under CS but the least
      under RM. The soil invertase activity decreased significantly under CG, and the
      soil urease activity had a significant decrease under SM, CG and RM. After ginger
      planting, the soil urease and intervase activities under CS were higher, as
      compared with those under the other cropping modes.

PMID- 22586970
TI  - [Effects of tillage mode on black soil's penetration resistance and bulk
      density].
AB  - Taking an eight-year field experiment site in Dehui County of Jilin Province,
      Northeast China as test object, this paper studied the effects of different
      tillage modes (no tillage and ploughing in autumn) on the penetration resistance
      and bulk density of black soil. No tillage increased the soil penetration
      resistance, especially at the soil depth of 2.5-17.5 cm. In the continuous
      cropping of maize and the rotation of maize-soybean, the maximum soil penetration
      resistance at planting zone under no tillage and ploughing in autumn was 2816 and
      1931 kPa, and 2660 and 2051 kPa, respectively, which had no restriction on the
      crop growth. The curve of soil penetration resistance under ploughing in autumn
      changed with ridge shape, while that under no tillage changed less. Comparing
      with ploughing in autumn, no tillage increased the bulk density of 5-20 cm soil
      layer significantly. Under no tillage, the bulk density of 5-30 cm soil layer
      changed little, but under ploughing in autumn, soil bulk density increased
      gradually with increasing soil depth. There was no significant correlation
      between soil bulk density and soil penetration resistance.

PMID- 22586971
TI  - [Relationships between soil nutrient contents and soil enzyme activities in Pinus
      massoniana stands with different ages in Three Gorges Reservoir Area].
AB  - Based on the measurements of soil nutrient contents and enzyme activities and the
      canonical correspondence analysis (CCA), this paper studied the relationships
      between soil nutrient contents and soil enzyme activities in different age Pinus
      massoniana stands in Three Gorges Reservoir Area. Among the test stands, mature
      stand had the highest contents of organic matter, total nitrogen, ammonium
      nitrogen, and available phosphorus in 0-20 cm soil layer, followed by middle-aged
      stand, and nearly-mature stand. With the increase of the stand age, soil
      invertase activity increased after an initial decrease, cellulase and
      polyphenoloxidase activities decreased gradually, while urease and peroxidase
      activities decreased after an initial increase. CCA analysis showed that the
      effects of the main soil parameters on the soil enzyme activities in the stands
      ranked in the sequence of total nitrogen > organic matter > pH > bulk density >
      ammonium nitrogen > available phosphorus. Soil invertase activity had significant
      positive correlations with soil organic matter, total nitrogen, and total
      phosphorus, while soil peroxidase activity significantly negatively correlated
      with soil organic matter, total nitrogen, total phosphorus, and bulk density. The
      soil was rich in main nutrients, invertase activity was relatively high, while
      peroxidase activity was relatively low. The activities of soil invertase,
      cellulase and peroxidase could be used as the good biological indicators in
      evaluating soil quality and fertility.

PMID- 22586972
TI  - [Prediction of regional soil quality based on mutual information theory
      integrated with decision tree algorithm].
AB  - In this paper, some main factors such as soil type, land use pattern, lithology
      type, topography, road, and industry type that affect soil quality were used to
      precisely obtain the spatial distribution characteristics of regional soil
      quality, mutual information theory was adopted to select the main environmental
      factors, and decision tree algorithm See 5.0 was applied to predict the grade of
      regional soil quality. The main factors affecting regional soil quality were soil
      type, land use, lithology type, distance to town, distance to water area,
      altitude, distance to road, and distance to industrial land. The prediction
      accuracy of the decision tree model with the variables selected by mutual
      information was obviously higher than that of the model with all variables, and,
      for the former model, whether of decision tree or of decision rule, its
      prediction accuracy was all higher than 80%. Based on the continuous and
      categorical data, the method of mutual information theory integrated with
      decision tree could not only reduce the number of input parameters for decision
      tree algorithm, but also predict and assess regional soil quality effectively.

PMID- 22586973
TI  - [Evaluation of land resources carrying capacity of development zone based on
      planning environment impact assessment].
AB  - Assessment of land resources carrying capacity is the key point of planning
      environment impact assessment and the main foundation to determine whether the
      planning could be implemented or not. With the help of the space analysis
      function of Geographic Information System, and selecting altitude, slope, land
      use type, distance from resident land, distance from main traffic roads, and
      distance from environmentally sensitive area as the sensitive factors, a
      comprehensive assessment on the ecological sensitivity and its spatial
      distribution in Zhangzhou Merchants Economic and Technological Development Zone,
      Fujian Province of East China was conducted, and the assessment results were
      combined with the planning land layout diagram for the ecological suitability
      analysis. In the Development Zone, 84.0% of resident land, 93.1% of industrial
      land, 86.0% of traffic land, and 76. 0% of other constructive lands in planning
      were located in insensitive and gently sensitive areas, and thus, the implement
      of the land use planning generally had little impact on the ecological
      environment, and the land resources in the planning area was able to meet the
      land use demand. The assessment of the population carrying capacity with
      ecological land as the limiting factor indicated that in considering the highly
      sensitive area and 60% of the moderately sensitive area as ecological land, the
      population within the Zone in the planning could reach 240000, and the available
      land area per capita could be 134.0 m2. Such a planned population scale is
      appropriate, according to the related standards of constructive land.

PMID- 22586974
TI  - [Eco-hydrological characteristics and soil and water conservation effect of
      citrus plantation on slope red soil of Jiangxi Province, China].
AB  - A 9-year observation was conducted at the experimental plots in the Citrus
      reticulata plantation in Jiangxi Provincial Eco-Technology Park to study the eco
      hydrological characteristics and soil conservation benefits of the plantation on
      slope red soil. Seven treatments were designed and monitored over nine years. The
      average flow and the rate of sediment for the seven treatments were reduced by
      78.5% and 77.2%, respectively. The reduction rates were the highest in treatments
      band coverage of Paspalum natatu, whole coverage of P. natatu, and level terrace
      with grass on ridge, with the values of 94.8%, 94.3% and 92.5%, respectively,
      followed by in treatment intercropping Glycine max (66.0%) and Raphanus sativus
      (77.5%), with horizontal planting being better than vertical planting, and the
      lowest in treatment without understory vegetation (33.1%). The observations on
      the precipitation redistribution of 43 rainfall events with a mean precipitation
      of 20.07 mm in 2009-2010 showed that the throughfall, stemflow, and canopy
      interception were 9.15, 4.72 and 6.20 mm, accounting for 44.7%, 25.7% and 29.6%
      of the precipitation, respectively. The throughfall and stemflow tended to
      increase with increasing precipitation. There was a significant liner negative
      correlation between the canopy interception rate and the precipitation when the
      rainfall was less than 10 mm, but no significant correlation when the rainfall
      was greater than 10 mm. The water holding rate of C. reticulata litters was
      logarithmically correlated with water soaking time, and the maximum water holding
      rate was 326%. It was considered that rational allocation of understory
      vegetation played an important role in the soil and water conservation of citrus
      orchard on slope red soil.

PMID- 22586975
TI  - [Optimization of conservation network system for inter-basin wetland ecosystem in
      Huang-Huai-Hai Region].
AB  - By using systematic conservation planning (SCP) method, and taking catchment as
      planning unit, an optimization of conservation network system for the inter-basin
      wetland ecosystem in Huang-Huai-Hai Region was conducted, with a comprehensive
      consideration of 3-dimensional (lateral, longitudinal and vertical) connectivity
      and Inter-basin Water Transfer Project and by the methods of irreplaceability
      analysis and gap identification. The efficacy of the optimized conservation
      network system was evaluated, as compared with the existing conservation network
      system. According to the principles of irreplaceability and connectivity, the
      wetland conservation gaps could be divided into two types, i.e. , be conserved in
      priority and in general. After the optimization, the conservation status of the
      inter-basin wetland ecosystem in Huang-Huai-Hai Region had an overall
      improvement. The conserved percentage of the wetland types was from about 20% up
      to 46.8%, and, for each wetland type, its conserved level increased to some
      extent, almost above 40%. Both in the near future and in the long term, more
      attention should be paid to the conservation of lake wetland. In addition, the
      integration of ecosystem service function and biodiversity and the combination of
      protection with restoration would be the main task for the wetland ecosystem
      conservation planning in the future.

PMID- 22586976
TI  - [Application of carrying capacity assessment in spatial allocation of regional
      population: a case of Changzhou City of East China].
AB  - Based on the spatial differences in urban ecosystem carrying capacity, and by
      using geographic information system (GIS) spatial analysis technology and system
      dynamics (SD) model, this paper ascertained the moderate population size in urban
      area and its subareas, and presented an alternative method for quantitatively
      allocate the population. This method was applied in Changzhou, a city with more
      than three million populations in East China. A SD model consisted of population,
      economy, land and environment modules for the city was established and scenario
      analysis was made. The results showed that under the requirements of satisfying
      both economic development and environmental protection, the total population in
      the city in 2050 would reach nearly 4 million, and according to the differences
      in the urban ecosystem carrying capacity, a spatial allocation pattern of 2.4
      million populations in main city and 150000-400000 populations in each of 5 new
      towns was proposed. This study could provide scientific support for the spatial
      allocation of population and economy in country land development and management.

PMID- 22586977
TI  - [Breeding habitat characteristics of red-crowned crane at Zhalong of Northeast
      China: a multi-scale approach based on TM and ASAR image data].
AB  - Based on the Landsat TM and Envisat ASAR HH/HV imagery data and by using the GPS
      data of red-crowned crane nesting sites (n = 28) at Zhalong National Nature
      Reserve of Northeast China, the models of the breeding habitat selection of red
      crowned crane at the Reserve were established by binary Logistic regression to
      identify the key variables for the habitat selection at eight spatial scales (30
      240 m). The relative performance of the two models based on the Landsat TM and
      Envisat ASAR HH/HV databases was compared, and the prediction capacity of the
      models across the eight scales was approached. The overall precisions of the two
      models were satisfactory (> or = 69.0%). At scale 30 m, only variable TCA_2
      entered with negative value into the model based on Landsat TM database, which
      indicated that the crane at this scale avoided selecting higher density reed
      marshes. At scales 60-120 m, the variable PCA_2 entered with positive value into
      the two models, indicating that the crane at these scales had higher demand of
      high density reed marshes to improve its concealment. At scale 90 m, the variable
      HV backward scatting coefficient also entered into the combined model, which
      indicated that water condition was the important factor for the habitat selection
      of the crane at this scale. At scales > 120 m, the texture information of the two
      satellite sensors started to be involved into the two models, indicating that at
      larger scales, the crane had decreasing demand on the vegetation features for its
      breeding habitat selection but increasing sensitivity to the anthropogenic
      disturbance factors. The introduction of ASAR variables into the models increased
      the prediction accuracy of the models markedly at all scales.

PMID- 22586978
TI  - [Emergy of agro-ecosystem in Hunan Province: evolution and trend].
AB  - By using emergy analysis method, a trend analysis was made on the total emergy,
      its input-output structure, and emergy indices of the agro-ecosystem in Hunan
      Province of South-central China from 1999 to 2008. In the study period, the
      available total emergy input of the ecosystem was basically maintained at a
      stable level, but the input structure changed with the input of non-renewable
      industrial auxiliary emergy increased from 4.00E+22 sej in 1999 to 5.53E+22 sej
      in 2008, while that of renewable organic emergy decreased from 1.32E+23 sej to
      1.20E+23 sej. Both the total emergy output and the output efficiency of the
      ecosystem had a great increase, with the total output reached 1.69E+23 sej in
      2008, which was 23.8% higher than that in 1999, and the net output ratio
      increased from 0.79 to 0.96. Owing to the ever-increasing trend of the
      environmental loading ratio which was from 1.12 to 1.79, the sustainable
      development index of the ecosystem presented a decreasing trend, from 0.71 to
      0.54, indicating that the agriculture in Hunan Province was overall belonged to
      the type of ecosystem driven by high consumption, and had relatively apparent
      extensive development characteristics.

PMID- 22586979
TI  - [Effects of high temperature on the mortality and fecundity of two co-existing
      cotton aphid species Aphis gossypii Glover and Acyrthosiphon gossypii Mordvilko].
AB  - Aphis gossypii and Acyrthosiphon gossypii are the coexisting species on cotton
      plant, with their abundance differed within and among years. To explore whether
      the abundance difference was related to the different responses of the two aphid
      species to high temperature, a laboratory experiment was conducted to assess the
      mortality and reproduction of the two aphid species at high temperatures 32, 34,
      36 and 38 degrees C. With the increasing temperature and prolonged exposure
      period, the cumulative mortality of the two aphid species increased, and
      Acyrthosiphon gossypii had a higher cumulative mortality than Aphis gossypii. The
      daily mortality of the aphids could be well simulated by complementary log-log
      (CLL) model. The median lethal temperature of the two aphid species estimated by
      CLL model decreased with prolonged exposure period. Under the same exposure
      period, the median lethal temperature of Aphis gossypii was higher than that of
      Acyrthosiphon gossypii. Within the range of 32-38 degrees C, the reproduction
      rate of the two aphid species decreased with increasing temperature, but Aphis
      gossypii had a significantly higher reproduction rate than Acyrthosiphon
      gossypii, indicating that at the temperature higher than 32 degrees C, Aphis
      gossypi had higher tolerance against high temperature than Acyrthosiphon
      gossypii, and consequently, had more competitive advantage under global warming.

PMID- 22586980
TI  - [Diversity of antagonistic bacteria isolated from rhizosphere of several cash
      crops].
AB  - By adopting antimicrobial spectrum test, BOXAIR-PCR, physiological and
      biochemical, and 16S rDNA sequencing analysis, this paper analyzed the diversity
      of 55 antagonistic bacterial strains isolated from the rhizosphere of 10 cash
      crops. There was a high diversity of the antagonism of the strains. Based on
      BOXAIR-PCR, all the strains were clustered into 7 groups at the similarity level
      of 72.1%, and divided into 25 groups at the similarity level of 85.0%. All the
      strains belonged to Bacillus, Paenibacillus, Brevibacillus, Pseudomonas and
      Alcaligenes, respectively. The antagonistic bacteria isolated from the
      rhizosphere had high genetic diversity and high diversity in antagonistic
      activity.

PMID- 22586981
TI  - [Stress resistance and genetic diversity of endophytic bacteria isolated from
      Caragana spp. root nodules].
AB  - By adopting PCR-RFLP and 16S rDNA sequencing, this paper analyzed the genetic
      diversity and phylogeny of 40 endophytic bacterial strains isolated from Caragana
      spp. root nodules, and determined the salt resistance, acid- and alkali
      resistance, and growth temperature range of the strains. A total of 9 genotypes
      were obtained from the 40 strains by RFLP. The 16S rDNA sequencing, morphological
      observation, and biochemical test of representative strains showed that the
      strains belonged to Bacillus, Inquilinus, Shinella and Acinetobacter,
      respectively, and had rich genetic diversity. 57.5% of the strains could tolerate
      4% NaCl stress, 75% of the strains could grow in YMA medium with an initial pH
      11.0, and 85% of the strains could survive after heat shock treatment at 60
      degrees C, suggesting that the endophytic bacteria of Caragana spp. had strong
      resistance capacity. Among the strains, LWEN 07 and LWEN 15 were most resistant.

PMID- 22586982
TI  - [Residue of chlorpyrifos and its degradation dynamics in Chinese chive (Allium
      tuberosum) plant and soil].
AB  - This paper studied the residue of chlorpyrifos and its degradation dynamics in
      Chinese chive (Allium tuberosum) plant and soil after irrigating different
      concentrations of this pesticide into A. tuberosum root zone under plastic
      greenhouse and open-field cultivated conditions. The chlorpyrifos in A. tuberosum
      plant had a faster degradation rate than that in soil, with an average half-life
      of the pesticide being 3.41 and 7.40 days in the plant and soil, respectively.
      Under the conditions of plastic greenhouse and open-field cultivation, the
      degradation rate of chlorpyrifos in A. tuberosum plant had less difference, with
      the average half-life of chlorpyrifos being 3.37 and 3.44 days, respectively. 21
      days after irrigating into root zone, the chlorpyrifos (0.021-0.102 mg x kg(-1))
      in A. tuberosum plant did not exceed the maximum residue limit (< or = 0.01 mg x
      kg(-1), GB 2763-2005). A few chlorpyrifos residue was found in the new growth
      parts of A. tuberosum, but the residue concentration was obviously lower than
      that in the first harvested plant after irrigating this pesticide. The
      chlorpyrifos residue in soil had significant effects on the residue of the
      pesticide in A. tuberosum plant.

PMID- 22586983
TI  - [Biological activity of capsaicin and its effects on development and fecundity in
      Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae)].
AB  - Biological activity of capsaicin and its effects on development and fecundity in
      Bemisia tabaci were tested in the laboratory. The results showed that capsaicin
      induced direct mortality in different developmental stages of B. tabaci, and the
      mortality of whiteflies were significantly dosage-dependent. The toxicity of
      capsaicin to different developmental stages of B. tabaci by either leaf-dip or
      egg/larval-dip bioassays (the LC50 for adult, egg and nymph were 3525.79, 1603.29
      and 1526.27 mg x L(-1), respectively) was higher than that by systemic bioassay
      (the LC50 for adult, egg and nymph were 5360.04, 2359.19 and 5897.43 mg x L(-1),
      respectively), and toxicity of capsaicin to eggs was higher than to adults in
      both bioassay methods. 2000 and 4000 mg x L(-1) concentrations of capsaicin had
      strong antifeedant effect on B. tabaci, as exemplified by reduced honeydew
      excretion of adults feeding on leaves treated with capsaicin compared with
      untreated leaf discs. Capsaicin also had strong oviposition deterrence against B.
      tabaci, with 94. 2% of selective oviposition deterrence rate and 83. 0% of
      nonselective oviposition deterrence rate when exposed to 4000 mg x L(-1)
      concentration for 24 h. We did not find effect on development time of B. tabaci
      eggs and nymphs, and on molting rate of adults when exposed to capsaicin at 500,
      1000 and 2000 mg x L(-1) concentrations, however, exposure to 4000 mg x L(-1)
      concentration of capsaicin significantly affected development time of B. tabaci
      nymphs and molting rate of adults. Exposure to capsaicin also significantly
      reduced fecundity of B. tabaci adults, and this reduction was significantly
      dosage-dependent.

PMID- 22586984
TI  - [Dietary composition and food competition of six main fish species in rocky reef
      habitat off Gouqi Island].
AB  - Based on the monthly investigation data of fish resources in the rocky reef
      habitat off Gouqi Island from March 2009 to February 2010, this paper studied the
      dietary composition of three native fish species (Sebasticus marmoratus,
      Hexagrammos otakii and Hexagrammos agrammus) and three non-native fish species
      (Lateolabrax japonica, Nibea albiflora and Larimichthys polyactis). The analysis
      of gut content indicated that the main prey items of these six dominant fish
      species were Caprellidae, Gammaridea, juvenile S. marmoratus, Engraulis japonicas
      and Acetes chinensis and the dietary composition of each of the 6 fish species
      had obvious seasonal variation. There was an intense food competition between
      native species H. otakii and H. agrammus in autumn, between non-native species N.
      albiflora and L. polyactis in summer, between non-native species N. albiflora and
      native species S. marmoratus in autumn, and between non-native species N.
      albiflora and native species H. otakii in winter. It was suggested the non-native
      species N. albiflora was the key species in the food competition among the six
      dominant fish species in this rocky reef habitat, and thus the feeding behaviors
      of these six fish species could have definite effects on the resource capacity of
      juvenile S. marmoratus.

PMID- 22586985
TI  - [Community structure of fish in Zhoushan Fishing Ground and its adjacent waters
      in spring and summer].
AB  - Based on the investigation data of the fishery resources and environment in
      Zhoushan Fishing Ground and its adjacent waters in August 2006 and April 2007,
      and by using multi-dimensional scaling (MDS) and canonical correspondence
      analysis (CCA), this paper studied the species composition and the
      characteristics of fish community in the area. In spring, a total of 62 fish
      species were captured, belonging to 56 genera, 36 families and 11 orders. The
      dominant species were Amblychaeturichthys hexanema and Larimichthys polyactis,
      and their abundance occupied 82. 9% of the total. In summer, 58 fish species were
      captured, belonging to 51 genera, 38 families and 11 orders. Amblychaeturichthys
      hexanema, Champsodon snyderi, Dysomma anguillaaris and Acropoma japonicum were
      the dominant species, with the abundance accounted for 60.8% of the total. In the
      two seasons, twenty stations were separated into three groups. Among the fishes
      captured, 26 and 30 fish species had an occurrence rate larger than 5.0% in
      spring and summer, respectively, and formed two and three assemblages
      correspondingly.

PMID- 22586986
TI  - [Spatial distribution of wintering Engraulis japonicus and its relationship with
      the inter-annual variations of water temperature in central and southern Yellow
      Sea].
AB  - Abstract: This paper studied the inter-annual variations in the spatial
      distribution of wintering anchovy (Engraulis japonicus) in central and southern
      Yellow Sea, based on the 1986-2010 bottom trawl survey data and related sea
      surface temperature (SST) data obtained by remote sensing, and approached the
      relationships between the inter-annual variations in the spatial distribution of
      the wintering anchovy and the SST, by using GIS technique, spatial analysis and
      correlation analysis. In 1986-2010, the wintering anchovy in the study area had
      apparent inter-annual variations in spatial distribution, with its abundance
      dropped to the lowest level and its distribution moved shoreward in 2004, and the
      abundance rebounded and centralized in the eastern waters in 2010. The
      centralized distribution regions of the anchovy's capture locations and stock
      density in longitudinal and latitudinal directions also had apparent inter-annual
      variations. There was a significant correlation between the latitude of the
      anchovy's stock density center and the mean latitude of the representative
      isotherms, suggesting that the variations in water temperature had effects on the
      latitudinal distribution of the wintering anchovy, and whether the anchovy
      distributed shoreward or not was determined by the inter-annual variations of
      Yellow Sea Warm Current. Among the factors affecting the anchovy distribution,
      fishing pressure was the main factor affecting the changes in anchovy abundance,
      and water temperature mainly determined the changes in anchovy spatial
      distribution.

PMID- 22586987
TI  - [Characteristics of Pomacea canaliculata reproduction under natural conditions].
AB  - Abstract: A three-year breeding experiment was conducted in a paddy field in
      Zixing City of Hunan Province, South-central China to study the characteristics
      of golden apple snail (Pomacea canaliculata) reproduction under natural
      conditions. Under the natural conditions in southern Hunan Province, the snails
      could approximately reproduce three generations per year. The average sexual
      maturity periods of the first, the second, and the third generation of the female
      snails were 59.3, 45.4 and 213.0 days, respectively, and those of the male snails
      were 4.3 days earlier than the females'. The natural sex ratio of the females to
      the males was 1.54:1. The average copulation duration was 19.2 hours, but
      spawning did not always occur after each time of copulation. The number of the
      egg masses produced by the females per month was significantly positively
      correlated with the mean monthly air temperature (r = 0.756) , while the average
      incubation duration of the egg masses was significantly negatively correlated
      with the daily air temperature (gamma = -0.726x + 23.064, r = -0.980). The
      average incubation time of the egg masses was 20.7 days, average incubation rate
      was 44.1%, and the average life expectancy of the female and male snails was 2.40
      and 1.98 years, respectively. A female snail in its lifetime could averagely
      spawn 13764 eggs and reproduce 6070 young snails.

PMID- 22586988
TI  - [Underlying mechanisms and related techniques of stand establishment of cotton on
      coastal saline-alkali soil].
AB  - Stand establishment is the most difficult step for cotton planting on coastal
      saline-alkali soil. To establish and improve the techniques for stand
      establishment is the key in the production of high-yielding cotton on saline
      alkali soil. Based on the previous studies and our own research progress in this
      field, this paper reviewed the effects and the underlying mechanisms of making
      unequal salt distribution in root zone, increasing soil moisture and temperature,
      establishing under-mulching greenhouse, and introducing seed coating agent in
      promoting stand establishment of cotton on saline-alkali soil. It was suggested
      that under the conditions of the average salt content in topsoil being not able
      to reduce, improving at least partial root zone environment through the induction
      of unequal salt distribution in the root zone and increasing soil moisture and
      temperature could significantly reduce salt injury and improve stand
      establishment. Flat seeding under plastic mulching on low-salinity soil, furrow
      seeding with mulching on moderate- or high-salinity soil, early mulching before
      sowing on rain-fed saline soil, and late sowing of short-season cotton in heat
      limited area were the efficient techniques for improving the stand establishment
      of cotton on coastal saline-alkali soil. This review could provide full guarantee
      for the cotton stand establishment on coastal saline-alkali soil.

PMID- 22586989
TI  - [Roles of glucosinolates in the interrelationships between Brassicaceae plants
      and insects: a review].
AB  - Glucosinolates (GS) are the important secondary metabolites of Brassicaceae
      plants, playing an important role in regulating the interrelationships between
      Brassicaceae plants and insects. GS can protect Brassicaceae plants against
      euryphagous herbivorous pests because of the toxicity of GS and their breakdown
      products. However, oligophagous pests which have evolved manifold metabolic
      pathways to cope with the defensive compounds depended fully on GS and their
      volatile breakdown products for host-plant recognition and orientation. The GS
      ingested by herbivores are also toxic to carnivores, and can directly deter
      predators. On the other hand, predators and parasitoids are attracted by the
      volatile breakdown products of GS from the Brassicaceae plants damaged by
      herbivores. Based on the recent findings, this paper reviewed the defensive
      function of GS against herbivores, host selection of oligophagous pests, GS
      metabolic pathways of herbivores, induction of GS by herbivores, and effects of
      GS on the third tropic level. Future directions and techniques in this research
      field were also suggested.

PMID- 22586990
TI  - [Current advance in the topological structure and function of holin encoded by
      bacteriophage lambda--a review].
AB  - The holin-lysin two-step lysis system widely exists in double stranded DNA
      bacteriophages for the release of progeny bacteriophage from an infected
      bacterial cell at the final stage of phage infection. Lambda bacteriophage is a
      prototype for studying holin. The S gene in Lambda bacteriophage has a dual-start
      motif and encodes holin S105 and antiholin S107. Here, we reviewed the progress
      in topological structure of holin from Lambda bacteriophage and its formation of
      membrane lethal holes. We also discussed the potential of the holin in the
      control of bacterial infection.

PMID- 22586991
TI  - [Biosynthesis and regulation of mycolic acids in Mycobacterium tuberculosis--a
      review].
AB  - Tuberculosis (TB) is one of the world's deadliest diseases. Approximately eight
      million individuals develop active tuberculosis annually, and two million die of
      tuberculosis. The emergence of multi-drug resistance strains, HIV co-infection,
      and an increasing aging population further worsen this scenario. Mycolic acids
      (MAs, also mycolate) are integral cell wall components of Mycobacterium
      tuberculosis, other mycobacterium and most actinomycetes, engaging in the
      remarkable survival ability of Mycobacterium tuberculosis within infected hosts,
      virulence and evasion of immunity. The biosynthesis and regulation of mycolic
      acids are rife with anti-tuberculosis drug targets. First-line tuberculosis drugs
      such as isoniazid and ethambutol target this pathway. In-depth investigation of
      this aspect will provide more opportunities to find better measures to combat
      tuberculosis. To this end, we reviewed the structures, classification,
      biosynthesis pathway, regulation factors in pathway of mycolic acid, as well as
      promising drug targets.

PMID- 22586992
TI  - [Biosynthesis of geosmin and 2-methylisoborneol in the prokaryotes--a review].
AB  - The occurrence of off-flavor problems caused by prokaryotes cyanobacteria and
      actinomycetes is a worldwide water and food quality issue. Based on literatures
      on two earthy-muddy-smelling metabolites, (i. e., geosmin and 2-methylisoborneol
      (2-MIB)), we reviewed their chemical characteristics, biosynthetic pathways,
      genes and enzymes that are involved in biosynthesis. Then we discussed current
      research questions related to off-flavor and future directions. Finally, we
      addressed the significance of probable key regulatory mechanism for the
      production and release of geosmin and 2-MIB, which could provide more scientific
      strategies to better control off-flavors outbreaks in drinking and aquaculture
      water.

PMID- 22586993
TI  - [Isolation and identification of myxobacteria in the saline-alkaline soils of
      Akesu in Xinjiang].
AB  - OBJECTIVE: To isolate myxobacteria and investigate their diversity in saline
      alkaline soils from Akesu in Xinjiang. METHODS: Conventional culture-dependent
      methods, e. g. baiting technique, water agar, soil extract agar and mineral agar,
      were used to isolate myxobacteria from 25 soil samples collected from Akesu areas
      of Xinjiang. Combining with physicochemical properties (acidity/alkalinity, salt
      concentration, vegetation and geographical locations) of the soil samples,
      myxobacterial diversity was studied. RESULTS: In total 58 strains were isolated,
      and identified as belonging to 6 different genera, i.e. Myxococcus, Cystobacter,
      Corallococcus, Sorangium, Nannocystis and Polyangium of Myxococcales. The most
      frequent genus isolated was Myxococcus which may better adapt in harsh
      environments. Different myxobacterial diversity was detected in different
      habitat. CONCLUSION: Myxobacteria diversity was low in saline-alkaline soils of
      Akesu in Xinjiang.

PMID- 22586994
TI  - [Isolation and identification of Citrobacter freundii from diseased giant
      salamander, Andrias davidianus].
AB  - OBJECTIVE: To determine the pathogenic bacterium infecting giant salamander
      (Andrias davidianus). METHODS: Bacterium was isolated from the liver of diseased
      Chinese giant salamander and identified by the Biolog Microbial Identification
      System and molecular biology method. Healthy Chinese giant salamander and crucian
      carp were used for experimental infection with bacterial suspension. RESULTS: A
      bacterial strain JZ01 was isolated and identified from diseased giant salamander.
      Infection with the bacterial suspension to healthy giant salamander could
      reproduce the diseased symptoms as occurred naturally and the same bacterium
      could be recovered from these infected giant salamanders. The isolated bacterium
      also has certain pathogenicity to crucian carp. Identification by the Biolog
      Microbial Identification System, and further 16S rDNA sequence and phylogenetic
      analysis demonstrated that the bacterium isolated from diseased giant salamander
      was Citrobacter freundii. The susceptibility test to antibiotics demonstrated
      that the bacterial strain JZ01 was susceptible to aztreonam, cefepime and
      cefotamine. CONCLUSION: Citrobacter freundii is a pathogen for cultured Chinese
      giant salamander.

PMID- 22586995
TI  - [A novel bacterial cell-surface display system based on NCgl1221 from
      Corynebacterium glutamicum].
AB  - OBJECTIVE: To develop a novel Escherichia coli cell surface display system by
      using C-terminally truncated NCgl1221 as the anchoring protein, which greatly
      enriched or optimized the bacterial displayed systems. METHODS: We amplified the
      sequence of C-terminally truncated NCgl1221 and beta-amylase, and constructed the
      fusion expression vector. Then we transformed the recombinant plasmids PET-NA and
      PET-28a into Rosetta (DE3) pLysS. The fusion protein expression was induced by
      IPTG and identified by SDS-PAGE and Western blot analysis. The IPTG induced
      strains were immunostained and investigated by fluorescence microscope and flow
      cytometry to detect the displayed beta-amylase. Finally, we analyzed the activity
      of beta-amylase and starch hydrolization in order to determine whether the
      displayed beta-amylase has the activity or not. RESULTS: The fusion protein was
      successfully expressed in E. coli, and the active beta-amylase was displayed on
      the cell surface by fusing it to the C terminus of the anchor. The recombinant
      strain displaying beta-amylase can utilize soluble starch in the medium.
      CONCLUSION: A novel E. coli surface display system by using C-terminally
      truncated NCgl1221 as the anchor motif was successfully developed. The active
      enzyme with a molecular size of 56 kDa was displayed on E. coli by this system,
      which provided the basis for the application of the system in whole-cell
      biocatalyst or biosorbent.

PMID- 22586996
TI  - [Transient expression of Aeromonas hydrophila HBNUAh01 outer membrane protein A
      gene in tobacco leaf cells].
AB  - OBJECTIVE: To clone outer membrane protein A (ompA) gene from Aeromonas
      hydrophila HBNUAh01 and transiently express this protein in tobacco (Nicotiana
      tabacum) leaf cells. METHODS: A. hydrophila outer membrane protein A (AhompA)
      gene was amplified by PCR using A. hydrophila HBNUAh01 cells as template, and
      cloned into the pEASY-Blunt Simple vector for sequencing. After sequence
      confirmation, AhompA gene was inserted into expression vector pCAMBIA1300
      containing a yellow fluorescent protein (YFP) gene, to obtain a recombinant
      expression plasmid. The recombinant expression plasmid was introduced into
      Agrobacterium tumefaciens GV3101 competent cells, and the positive clones were
      transfected to tobacco leaf cells. The expression of yellow fluorescent protein
      fused with AhompA was observed by Confocal Laser Scanning Microscope, and the
      mRNA of AhompA was detected by RT-PCR. RESULTS: The AhompA gene cloned from A.
      hydrophila HBNUAh01 was 1032 bp. The fusion protein of AhompA and YFP was
      successfully expressed in tobacco leaf cells. CONCLUSION: The successful
      expression of the AhompA gene in tobacco leaf cells has laid a foundation for
      further investigation of prevention of limnobios diseases caused by A. hydrophila
      with plant vaccine.

PMID- 22586997
TI  - [A minicircle DNA vector-mediated siRNA to stably suppress hepatitis B virus
      replication and expression].
AB  - OBJECTIVE: We used a minicircle DNA vector system to express small interfering
      RNA (siRNA) and studied the inhibition of hepatitis B virus (HBV) replication and
      gene expression in vitro. METHODS: siRNA targeting HBV S gene (siHBS) was
      designed , synthesized and cloned into a minicircle DNA vector pMC. BESPX-MCS2.
      After sequencing, we transformed the recombinant pMC-H1-siHBS-U6 into E. coli
      ZYCY10P3S2T, and induced the degradation of its bacterial backbone by adding L
      arabinose into the bacterial growth medium. As expected, a minicircle RNA
      interference (RNAi) vector pmc-H1-siHBS-U6 was generated only consisting of gene
      expression cassette. Then pmc-H1-siHBS-U6 was co-transfected into Huh-7 cells
      with HBV expression vector pHBV1.3. ELISA and Real-time PCR were performed to
      evaluate the inhibition effect of the secretion of HBsAg and HBeAg and the levels
      of HBV DNA and mRNA in Huh-7 cells. RESULTS: We Successfully established the
      minicircle-based RNAi vector pmc-H1-siHBS-U6, which can significantly inhibit the
      secretion of HBsAg and HBeAg in Huh-7 cells for two to three weeks. Real-time PCR
      results show that HBV DNA and mRNA levels were also down-regulated about 71% and
      80%. CONCLUSION: The minicircle DNA-based RNAi vector pmc-H1-siHBS-U6 can
      suppress HBV replication and gene expression specifically, efficiently and
      steadily. Thus, this study provided us a new siRNA delivery system and a new gene
      therapy strategy of HBV infection.

PMID- 22586998
TI  - [Effect of casamino acid on intergeneric conjugation in rapamycin-producing
      Streptomyces hygroscopicus ATCC29253].
AB  - OBJECTIVE: Streptomyces hygroscopicus ATCC29253 has attracted much interests due
      to its capacity of producing various secondary metabolites with strong
      bioactivities, including immunosuppressant rapamycin, nigericin, hexaenes,
      elaiophylin and hygrocins. OBJECTIVE: To investigate biosynthetic pathway of
      these metabolites and construct high-yield strains by genetic engineering,
      establishment of a highly efficient genetic manipulation system is critically
      required in this strain. METHODS: We tested the effects of conjugation media and
      donor strains on conjugal transfer from Escherichia coli to S. hygroscopicus
      ATCC29253 and other Streptomycetes. RESULTS: We found that both casamino acid and
      MgCl2 supplemented in conjugation media improved conjugation frequency in S.
      hygroscopicus ATCC29253. A random experiment led to the disclosure of an optimal
      combination of casamino acid and MgCl2 by which the conjugation frequency in S.
      hygroscopicus reached 1.5 x 10(-4). Meanwhile, we also found significant changes
      in conjugation frequencies of S. lividans, S. albus and S. avermitilis when
      casamino acid was supplemented in conjugation media. CONCLUSION: Casamino acid
      has significant influence on conjugation frequency in not only S. hygroscopicus
      ATCC29253 but also other Streptomyces such as S. lividans, S. albus and S.
      avermitilis.

PMID- 22586999
TI  - [Effects of ammonium sulfate on the metabolism and K-feldspar weathering of two
      potassium-bearing mineral-solubilizing bacteria].
AB  - OBJECTIVE: To determine the best conditions for Bacillus globisporus Q12 and
      Rhizobium sp. Q32 to produce organic acids and extracellular polysaccharides,
      respectively, and further elucidate the weathering mechanism of the two potassium
      bearing mineral-solubilizing bacteria. METHODS: Different contents (0-1.2 g/L) of
      (NH4)2SO4 were added to media to analyze the ability of the strains to produce
      organic acids and extracellular polysaccharides, and assess the ability of Q12,
      Q32 and their mixture to dissolve potassium feldspar. Scanning electron
      microscope (SEM) was also used to observe the distribution of the bacterial cells
      on the surfaces of the feldspar and the mineral weathering. RESULTS: Results show
      that Bacillus globisporus Q12 produced more organic acids, when the contents of
      (NH4)2SO4 were 0.6 g/L; Rhizobium sp. Q32 produced more extracellular
      polysaccharides, when there was no (NH4)2SO4 in the media; and the mixture of two
      strains produced more organic acids and extracellular polysaccharides, when the
      contents of (NH4)2SO4 were 0.3 g/L. Mineral dissolution experiment showed that
      Bacillus globisporus Q12, Rhizobium sp. Q32 and the mixture (Q12 + Q32)
      significantly dissolved the feldspar and released the elements from the mineral,
      of which the mixture of Q12 and Q32 had the best weathering ability than strain
      Q12 or Q32; SEM also indicated that the mixture of Q12 and Q32 had more ability
      to weather feldspar than each tested strain. CONCLUSION: The contents of
      (NH4)2SO4 in the media could affect the growth and metabolites of the strains Q12
      and Q32 and the mineral bioweathering, the mixture of strains Q12 and Q32 had the
      more potential of feldspar weathering through the combined action of organic
      acids and extracellular polysaccharides produced by strains Q12 and Q32.

PMID- 22587000
TI  - [Cloning, expression and characterization of the nucleotidylyltransferase gene
      amiE in amicetin biosynthesis].
AB  - OBJECTIVE: The aim of this study is to clone and express the
      nucleotidylytransferase encoding gene-amiE from the biosynthetic gene cluster of
      amicetin, a disaccharide nucleoside antibiotic, and to characterize AmiE in
      vitro. METHODS: The amiE, encoding a nucleotidylytransferase of 257 amino acid,
      was PCR amplified and cloned into pET28a, resulting in the plasmid pCSG4001,
      which was transformed into E. coli BL21(DE3) for expressing N-(His)6-tag AmiE.
      The recombinant AmiE was purified by affinity chromatography via AKTA Purifier 10
      system. The AmiE-catalyzed reactions were performed using TTP (or UTP) and
      glucose-1-phosphate as substrates. The enzyme assays were analyzed by HPLC; the
      substrate flexibility of AmiE was probed with three unnatural sugars-1-phosphate,
      including galactose-1-phosphate, galactosamine-1-phosphate and mannos-1
      phosphate. RESULTS: The N-(His)6-tag AmiE was expressed in E. coli in soluble
      form and was successfully purified via Ni2+ mediated affinity chromatography; in
      vitro biochemical experiments showed that AmiE could convert glucose-1-phosphate
      into TDP-glucose (or UDP-glucose) in the presence of TTP (or UTP). However,
      galactose-1-phosphate, galactosamine-1-phosphate and mannos-1-phosphate were not
      substrates of AmiE. CONCLUSION: The amiE was successfully cloned and expressed in
      E. coli, and the purified AmiE was biochemically confirmed to be a
      nucleotylyltransferase in amicetin biosynthesis pathway.

PMID- 22587001
TI  - [Clostridium sp. MH18 strain induces the formation of carbonate minerals].
AB  - OBJECTIVE: We studied the formation of carbonate minerals by bacteria to
      understand the mechanism of microbial mineralization. METHODS: Cultures of
      carbonate precipitation using Lagoa Vermelha medium with 6:1 molar ratio of Mg/Ca
      within 35 days were made under the mediation of Clostridium sp. (MH18 strain)
      isolated from soil. At the same time, aseptic experiments without the inoculation
      were done as the control. Mineral species were determined by X-ray diffraction,
      and the morphologies of precipitated carbonates were observed using optical
      microscopy and scanning electron microscopy. RESULTS: In the LV medium, MH18
      strain mediated the formation of carbonate mineral, in which high-magnesium
      calcite was dominant. In the initial stage, the minerals had shapes with dumbbell
      like morphology, and finally transformed to spheres. Only a small amount of
      precipitation appeared in the control, but X-ray diffraction patterns showed that
      these precipitations were amorphous substance. CONCLUSIONS: MH18 strain could
      induce crystallization of carbonate.

PMID- 22587002
TI  - [Morphological and biochemical changes of Microcystis aeruginosa PCC7806
      subjected to dark and oxygen limitation].
AB  - OBJECTIVE: To explore the mechanism of cell death in Microcystis aeruginosa PCC
      7806. METHOD: According to the water environment of the later period of algal
      bloom, M. aeruginosa PCC 7806 was treat with dark and O2 limitation. We observed
      the morphological changes using transmission electron microscope (TEM) and
      detected the reactive oxygen species (ROS) activity and Caspase3 activity in M.
      aeruginosa PCC7806 subjected to dark and O2 limitation. DNA status was also
      examined with the methods of Terminal deoxynucleotidyl transferase-mediated dUTP
      nick end-labeling (TUNEL) and agarose gel electrophoresis. RESULT: Massive algae
      cell died after 48 h treatment under dark and O2 limitation. During cell death
      process, we observed some changes of cell organelles including ribosomes and
      thylakoids disorganization, cytoplasmic vacuolation, nucleoplasm diffusion and
      plasmolysis in M. aeruginosa PCC7806 subjected to darkness and O2 limitation.
      Meanwhile, we found that increased ROS reactivity and capase 3 activity were
      related to the cell death process of M. aeruginosa. DNA breakage and
      fragmentation were proved by TUNEL staining and agarose gel electrophoresis
      during cell death process. CONCLUSION: All results showed that cell death with
      characteristics similar to eukaryotic programmed cell death could be induced in
      M. aeruginosa PCC 7806 after treatment with darkness and O2 limitation.
      Therefore, we suggested that the mechanism of cell death are conserved during
      evolution according to the characteristics of cell death shared between
      eukaryotes and Microcystis.

PMID- 22587003
TI  - [Isolation and characterization of a lytic bacteriophage from Mingyong glacier
      melt water].
AB  - OBJECTIVE: Glacier is a unique ecological system. This study focused on the
      isolation and characterization of a cold-active bateriophage from Mingyong
      glacier area in northwest Yunnan. METHODS: Bacterial strains isolated from
      glacial melt water were used as host cells to isolate and purify bacteriophages
      by double-layer plate method. The morphology of the isolated phages and their
      host strains were observed by electron microscope. Restriction fragment length
      polymorphism (RFLP) analysis of genomic DNA, constituent proteins and
      physiological analysis of the bacteriophages were further carried out to
      characterize the phages. RESULTS: A lytic cold-active bacteriophage, designated
      as MYSP03, was isolated from Mingyong glacier. Its host strain MYB03 was
      identified as a member of genus Flavobacterium, based on the 16S rRNA sequence
      analysis. The bacteriophage MYSP03 has a isometric head (about 72 nm in diameter)
      and a long tail (about 240 nm in length and 10 nm in width), but no envelope was
      detected. Physiological analysis results showed that MYSP03 had infection
      activity at 4 degrees C, and clear and transparent plaques were formed on double
      layer plates between 4 and 20 degrees C. Its optimum infection temperature was 10
      degrees C and optimal pH 9.4, respectively. It is insensitive to chloroform.
      Furthermore, the genome of MYSP03 consists of double-stranded DNA and is
      approximately 66 kb.

PMID- 22587004
TI  - [Screening of beta-lactoglobulin allergy-modulating lactobacilli strains using in
      vitro-in vivo correlation].
AB  - OBJECTIVE: We investigated the correlation between the in vitro immune profiling
      of 5 lactobacilli strains and their in vivo protective effect in a mouse beta
      lactoglobulin (BLG) allergy model for selecting the candidate strains with
      potential anti-allergy activity. METHODS: In vitro immunomodulation was assessed
      by measuring interleukin (IL)-4 and interferon gamma (IFN-gamma) release by
      primary lymphocytes stimulated with 5 active/heat-killed lactobacilli. A mice
      model of beta-lactoglobulin allergy was then used to evaluate the alleviating
      allergy capacity of the same set of strains. The rats were randomly divided into
      blank group, BLG allergy group and different lactobacilli strains group. The
      total IgE and BLG-specific IgE contents in the serum of rats were measured with
      ELISA. Splenic lymphocytes were isolated and cultured in vitro, the levels of
      Thl/Th2 type cytokine were detected by ELISA. RESULTS: Protection of BLG-induced
      allergy was strain-specific. The strains displaying an in vitro capacity to
      induce higher levels of the Thl type cytokine (IFN-gamma) and lower levels of the
      Th2 type cytokine (IL-4), significantly decreased the levels of total IgE and BLG
      IgE in allergic rat serum (P<0.05). In contrast, strains leading to a low IFN
      gamma/IL-4 cytokine ratio could not significantly attenuate allergic symptoms.
      CONCLUSION: We could predict the in vivo protective capacity of the studied
      lactobacilli strains based on the cytokine profile established in vitro. Oral
      consumption of specific strain may be effective in preventing and alleviating BLG
      allergic symptoms by the improvement of the Th1/Th2 cell balance toward Th1
      dominance, and the inhibition of IgE production.

PMID- 22587005
TI  - [Identification and biological characterization of an acetonitrile degrading
      strain].
AB  - OBJECTIVE: To identify and characterize an acetonitrile degrading strain BX2,
      thus to assess its potentials in the treatment of acetonitrile containing
      wastewater. METHODS: By means of phenotype and physio-biochemical
      characterization as well as phylogenetic analysis, we identified strain BX2. The
      optimum culture conditions of the strain were studied with single factor test,
      and the degradation of acetonitrile under the optimal growth conditions was
      determined. Additionally, NaCl tolerance was investigated. RESULTS: The phenotype
      and physio-biochemical characteristics of strain BX2 were similar to those of
      Rhodococcus sp.. The phylogenetic analysis based on 16S rRNA, gyrB and secA1 gene
      suggested strain BX2 was the closest relative of Rhodococcus rhodochrous with
      99.37%, 99.29% and 97.87% sequence similarity respectively. The optimal
      conditions for cell growth were 35 degrees C, initial pH 7.5, and 1% inoculum.
      Under these conditions, the degradation rate of acetonitrile was 95.87% (800mg/L)
      within 16 h. Strain BX2 was able to grow in defined medium containing NaCl up to
      6%. CONCLUSION: Strain BX2 was identified as Rhodococcus rhodochrous and named
      Rhodococcus rhodochrous BX2. It showed great environmental adaptation and high
      capability of degrading acetonitrile.

PMID- 22587006
TI  - [Isolation and function of genes regulating aphB expression in Vibrio cholerae].
AB  - OBJECTIVE: We identified genes that regulate the expression of aphB, the gene
      encoding a key virulence regulator in Vibrio cholerae O1 E1 Tor C6706(-).
      METHODS: We constructed a transposon library in V. cholerae C6706 strain
      containing a P(aphB)-luxCDABE and P(aphB)-lacZ transcriptional reporter plasmids.
      Using a chemiluminescence imager system, we rapidly detected aphB promoter
      expression level at a large scale. We then sequenced the transposon insertion
      sites by arbitrary PCR and sequencing analysis. RESULTS: We obtained two
      candidate mutants T1 and T2 which displayed reduced aphB expression from
      approximately 40,000 transposon insertion mutants. Sequencing analysis shows that
      Tn inserted in vc1585 reading frame in the T1 mutant and Tn inserted in the end
      of coding sequence of vc1602 in the T2 mutant. CONCLUSION: By using a genetic
      screen, we identified two potential genes that may involve in regulation of the
      expression of the key virulence regulator AphB. This study sheds light on our
      further investigation to fully understand V. cholerae virulence gene regulatory
      cascades.

PMID- 22587007
TI  - [Development and application of a new p1-based genotyping method for Mycoplasma
      pneumoniae].
AB  - OBJECTIVE To develop a PCR method for detecting the newly reported genotype
      (variant 2c, V2c) of Mycoplasma pneumoniae strains. METHODS: Specific primer was
      designed for detecting the V2c type based on the variant region of V2c strain p1
      gene. A nested multiple PCR method for V2c strain detection was set up and
      confirmed by related gene sequencing. In total 214 clinical strains isolated from
      Beijing between 2008 and 2011 were analyzed by this typing method. RESULTS: Nest
      multiple PCR typing method is effective to detect the V2c strain. Of the 214 M.
      pneumoniae strains 90.2% (193/214) were type 1, 0.9% (2/214) were variant 2a, and
      8.9% (19/214) were V2c. No type 2 was detected. CONCLUSION: This typing method is
      effective to distinguish the V2c strains from other variant M. pneumoniae
      strains, and important for the epidemiological study of Mycoplasma pneumonia
      infection.

PMID- 22587008
TI  - Amplified protein detection and identification through DNA-conjugated M13
      bacteriophage.
AB  - Sensitive protein detection and accurate identification continues to be in great
      demand for disease screening in clinical and laboratory settings. For these
      diagnostics to be of clinical value, it is necessary to develop sensors that have
      high sensitivity but favorable cost-to-benefit ratios. However, many of these
      sensing platforms are thermally unstable or require significant materials
      synthesis, engineering, or fabrication. Recently, we demonstrated that naturally
      occurring M13 bacteriophage can serve as biological scaffolds for engineering
      protein diagnostics. These viruses have five copies of the pIII protein, which
      can bind specifically to target antigens, and thousands of pVIII coat proteins,
      which can be genetically or chemically modified to react with signal-producing
      materials, such as plasmon-shifting gold nanoparticles (Au NPs). In this report,
      we show that DNA-conjugated M13 bacteriophage can act as inexpensive protein
      sensors that can rapidly induce a color change in the presence of a target
      protein yet also offer the ability to identify the detected antigen in a separate
      step. Many copies of a specific DNA oligonucleotide were appended to each virus
      to create phage-DNA conjugates that can hybridize with DNA-conjugated gold
      nanoparticles. In the case of a colorimetric positive result, the identity of the
      antigen can also be easily determined by using a DNA microarray. This saves
      precious resources by establishing a rapid, quantitative method to first screen
      for the presence of antigen followed by a highly specific typing assay if
      necessary.

PMID- 22587009
TI  - Hybrids of organic molecules and flat, oxide-free silicon: high-density
      monolayers, electronic properties, and functionalization.
AB  - Since the first report of Si-C bound organic monolayers on oxide-free Si almost
      two decades ago, a substantial amount of research has focused on studying the
      fundamental mechanical and electronic properties of these Si/molecule surfaces
      and interfaces. This feature article covers three closely related topics,
      including recent advances in achieving high-density organic monolayers (i.e.,
      atomic coverage >55%) on oxide-free Si(111) substrates, an overview of progress
      in the fundamental understanding of the energetics and electronic properties of
      hybrid Si/molecule systems, and a brief summary of recent examples of subsequent
      functionalization on these high-density monolayers, which can significantly
      expand the range of applicability. Taken together, these topics provide an
      overview of the present status of this active area of research.

PMID- 22587010
TI  - A totally synthetic, self-assembling, adjuvant-free MUC1 glycopeptide vaccine for
      cancer therapy.
AB  - In the development of vaccines for epithelial tumors, the key targets are MUC1
      proteins, which have a variable number of tandem repeats (VNTR) bearing tumor
      associated carbohydrate antigens (TACAs), such as Tn and STn. A major obstacle in
      vaccine development is the low immunogenicity of the short MUC1 peptide. To
      overcome this obstacle, we designed, synthesized, and evaluated several totally
      synthetic self-adjuvanting vaccine candidates with self-assembly domains. These
      vaccine candidates aggregated into fibrils and displayed multivalent B-cell
      epitopes under mild conditions. Glycosylation of Tn antigen on the Thr residue of
      PDTRP sequence in MUC1 VNTR led to effective immune response. These vaccines
      elicited a high level antibody response without any adjuvant and induced
      antibodies that recognized human breast tumor cells. These vaccines appeared to
      act through a T-cell independent pathway and were associated with the activation
      of cytotoxic T cells. These fully synthetic, molecularly defined vaccine
      candidates had several features that hold promise for anticancer therapy.

PMID- 22587011
TI  - Cytochrome P450 3A4 inhibition by ketoconazole: tackling the problem of ligand
      cooperativity using molecular dynamics simulations and free-energy calculations.
AB  - Cytochrome P450 3A4 (CYP3A4) metabolizes more than 50% of clinically used drugs
      and is often involved in adverse drug-drug interactions. It displays atypical
      binding and kinetic behavior toward a number of ligands characterized by a
      sigmoidal shape of the corresponding titration curves, which is indicative of a
      positive homotropic cooperativity. This requires a participation of at least two
      ligand molecules, whereby the binding of the first ligand molecule increases the
      affinity of CYP3A4 for the binding of the second ligand molecule. In the current
      study, a combination of molecular dynamics simulations and free-energy
      calculations was applied to elucidate the physicochemical origin of the observed
      positive homotropic cooperativity in ketoconazole binding to CYP3A4. The binding
      of the first ketoconazole molecule was established to increase the affinity for
      the binding of the second ketoconazole molecule by 5 kJ mol(-1), which explains
      and quantifies the experimentally observed cooperative behavior of CYP3A4. Shape
      complementarity through nonpolar van der Waals interactions was identified as the
      main driving force of this binding, which seems to be in line with the
      promiscuous nature of CYP3A4. Moreover, the calculated binding free energies were
      found to be in good agreement with the values predicted from a simple 2-ligand
      binding kinetic model as well as to successfully reproduce the experimental
      titration curve. This confirms the general applicability of rapid free-energy
      methods to study challenging biomolecular systems like cytochromes P450, which
      are characterized by a large flexibility and malleability of their active sites.

PMID- 22587012
TI  - The impact of preoperative total parenteral nutrition on early complications
      after surgery for Crohn's disease.

PMID- 22587013
TI  - InGaN/GaN multiple quantum wells grown on nonpolar facets of vertical GaN nanorod
      arrays.
AB  - Uniform GaN nanorod arrays are grown vertically by selective area growth on (left
      angle bracket 0001 right angle bracket) substrates. The GaN nanorods present six
      nonpolar {1-100} facets, which serve as growth surfaces for InGaN-based light
      emitting diode quantum well active regions. Compared to growth on the polar
      {0001} plane, the piezoelectric fields in the multiple quantum wells (MQWs) can
      be eliminated when they are grown on nonpolar planes. The capability of growing
      ordered GaN nanorod arrays with different rod densities is demonstrated. Light
      emission from InGaN/GaN MQWs grown on the nonpolar facets is investigated by
      photoluminescence. Local emission from MQWs grown on different regions of GaN
      nanorods is studied by cathodoluminescence (CL). The core-shell structure of MQWs
      grown on GaN nanorods is investigated by cross-sectional transmission electron
      microscopy in both axial and radial directions. The results show that the active
      MQWs are predominantly grown on nonpolar planes of GaN nanorods, consistent with
      the observations from CL. The results suggest that GaN nanorod arrays are
      suitable growth templates for efficient light-emitting diodes.

PMID- 22587015
TI  - Sodium periodate as a primary oxidant for water-oxidation catalysts.
AB  - Sodium periodate was characterized as a primary chemical oxidant for the
      catalytic evolution of oxygen at neutral pH using a variety of water-oxidation
      catalysts. The visible spectra of solutions formed from Cp*Ir(bpy)SO(4) during
      oxygen-evolution catalysis were measured. NMR spectroscopy suggests that the
      catalyst remains molecular after several turnovers with sodium periodate. Two of
      our [Cp*Ir(bis-NHC)][PF(6)](2) complexes, along with other literature catalysts,
      such as the manganese terpyridyl dimer, Hill's cobalt polyoxometallate, and
      Meyer's blue dimer, were also tested for activity. Sodium periodate was found to
      function only for water-oxidation catalysts with low overpotentials. This
      specificity is attributed to the relatively low oxidizing capability of sodium
      periodate solutions relative to solutions of other common primary oxidants.
      Studying oxygen-evolution catalysis by using sodium periodate as a primary
      oxidant may, therefore, provide preliminary evidence that a given catalyst has a
      low overpotential.

PMID- 22587014
TI  - Host carbon sources modulate cell wall architecture, drug resistance and
      virulence in a fungal pathogen.
AB  - The survival of all microbes depends upon their ability to respond to
      environmental challenges. To establish infection, pathogens such as Candida
      albicans must mount effective stress responses to counter host defences while
      adapting to dynamic changes in nutrient status within host niches. Studies of C.
      albicans stress adaptation have generally been performed on glucose-grown cells,
      leaving the effects of alternative carbon sources upon stress resistance largely
      unexplored. We have shown that growth on alternative carbon sources, such as
      lactate, strongly influence the resistance of C. albicans to antifungal drugs,
      osmotic and cell wall stresses. Similar trends were observed in clinical isolates
      and other pathogenic Candida species. The increased stress resistance of C.
      albicans was not dependent on key stress (Hog1) and cell integrity (Mkc1)
      signalling pathways. Instead, increased stress resistance was promoted by major
      changes in the architecture and biophysical properties of the cell wall. Glucose-
      and lactate-grown cells displayed significant differences in cell wall mass,
      ultrastructure, elasticity and adhesion. Changes in carbon source also altered
      the virulence of C. albicans in models of systemic candidiasis and vaginitis,
      confirming the importance of alternative carbon sources within host niches during
      C. albicans infections.

PMID- 22587017
TI  - In vivo, in vitro toxicity and in vitro angiogenic inhibition of sunitinib
      malate.
AB  - PURPOSE: To evaluate the in vivo and in vitro toxicity of sunitinib malate, a
      multikinase inhibitor molecule. DESIGN: Experimental, Prospective, Controlled.
      METHODS: Human retinal pigment epithelial (ARPE-19) and human umbilical vein
      endothelialcells (HUVECS) were used in a culture toxicity test and exposed to
      different concentrations of sunitinib malate for 18 hours. The HUVECs also were
      cultured to evaluate the angiogenesis inhibitory effect of sunitinib malate.
      Fundus photography and angiographic, electrophysiologic, and histopathologic
      evaluations with light and electron microscopy were performed in two groups of
      five rabbits each that received different intravitreal concentrations of the
      drug. Each rabbit received 0.1 ml of sunitinib malate in the right eye (one group
      with 12.5 mg/ml, the other group with 25 mg/ml); all animals received 0.1 ml of
      physiologic saline solution in the left eye. After sacrifice, the eyes were
      enucleated and fixed with modified Karnovsky solution. RESULTS: No toxicity
      related to sunitinib malate was observed using an in vitro model with the 12.5
      and 25 mg/ml solutions in HUVEC and ARPE cell cultures. No toxicity was observed
      in the in vivo model with 12.5 mg/ml, but light microscopy showed that the 25
      mg/ml solution damaged the photoreceptors layer. No functional changes in the
      electroretinogram were observed in any group. CONCLUSIONS: Sunitinib malate 12.5
      mg/ml caused no toxicity in in vivo and in vitro models, but the 25 mg/ml
      concentration caused retinal changes suggesting toxicity in the in vivo model.
      Further research with the drug is needed in models of ocular neovascularization.

PMID- 22587016
TI  - Associations of alcohol, nicotine, cannabis, and drug use/dependence with
      educational attainment: evidence from cotwin-control analyses.
AB  - BACKGROUND: Although substance use is associated with reduced educational
      attainment, this association may be owing to common risk factors such as
      socioeconomic disadvantage. We tested whether alcohol, nicotine, and illicit drug
      use and dependence were associated with lifetime educational attainment after
      controlling for familial background characteristics. METHODS: Data were from a
      1987 questionnaire and a 1992 telephone diagnostic interview of 6,242 male twins
      (n = 3,121 pairs; mean age = 41.9 years in 1992) who served in the U.S. military
      during the Vietnam era and therefore, were eligible for educational benefits
      after military service. Reduced educational attainment (<16 years) was examined
      in twin pairs discordant for substance use history. Substance use and dependence
      risk factors assessed were early alcohol and cannabis use, daily nicotine use,
      lifetime cannabis use, and alcohol, nicotine, cannabis, and any illicit drug
      dependence. RESULTS: Three significant differences were observed between at-risk
      twins and their cotwins: Compared to their low-risk cotwins, likelihood of
      completing <16 years of education was significantly increased for the following:
      (i) twins who used alcohol before age 18 (adjusted OR = 1.44; 95% CI: 1.02 to
      2.05), (ii) twins with a lifetime alcohol dependence diagnosis (adjusted OR =
      1.76; 95% CI: 1.27 to 2.44), and (iii) twins who had used nicotine daily for 30
      or more days (adjusted OR = 2.54, 95% CI: 1.55 to 4.17). However, no differences
      in education were observed among twin pairs discordant for cannabis initiation,
      early cannabis use, or cannabis, nicotine, or any illicit drug dependence.
      CONCLUSIONS: Even in a veteran population with access to military educational
      benefits, early alcohol use, alcohol dependence, and daily nicotine use remained
      significantly associated with years of education after controlling for shared
      familial contributions to educational attainment. The association between other
      substances and educational attainment was explained by familial factors common to
      these substance use phenotypes and adult educational attainment.

PMID- 22587018
TI  - In this issue of the International Reviews of Immunology.
AB  - This issue hosts diverse topics, from myeloid derived suppressor cells (MDSC)
      with their mechanism and role in cancer, the interplay between diet and emerging
      allergies studied in a genetically closed population, the pleiotropic anti
      inflammatory effects of resveratrol, to the quest to achieve more reliable immune
      correlates of protection against the hepatitis C virus (HCV).

PMID- 22587019
TI  - Amino acid metabolism related to immune tolerance by MDSCs.
AB  - Myeloid-derived suppressor cells (MDSCs) are present in most cancer patients. Due
      to their significant role in blocking immune responses, MDSCs are strategic
      obstacles to immunotherapy that require activation of the host's cell-mediated
      and innate immune responses. Following a brief description of the
      immunosuppressive MDSCs, the authors review the discovered mechanisms of amino
      acid metabolism that MDSCs use to suppress the activation of T cells. Given the
      heterogeneity of MDSCs and the variety of suppressive mechanisms employed by
      MDSCs, it is essential to understand which group of these cells and mechanisms
      are dominant.

PMID- 22587020
TI  - The interplay between diet and emerging allergy: what can we learn from
      Indigenous Australians?
AB  - The pathophysiology of atopic diseases, including asthma and allergy, is the
      result of complex gene-environment interactions. Since European colonization the
      Indigenous population of Australia has undergone significant changes with respect
      to their lifestyle as hunter-gatherers. These changes have had a detrimental
      effect on Aboriginal health, in part due to immunological modification. This
      review provides a comparative look at both the traditional Aboriginal/Indigenous
      diet and modern Western diets, examines some common allergies increasingly
      reported in contemporary Indigenous populations, and reviews concepts such the
      effect of vitamin deficiencies and changes in gut microbiota on immune function.

PMID- 22587021
TI  - Anti-inflammatory effects of resveratrol and its potential use in therapy of
      immune-mediated diseases.
AB  - A molecule with a relatively simple chemical structure, resveratrol has been
      found to interact with multiple molecular targets, many of them associated with
      inflammation and immunity. Indeed, it has been shown to act directly on central
      players of both innate and adaptive immunity, such as macrophages, lymphocytes,
      and dendritic cells. In addition, there is very little evidence suggesting
      significant deleterious side effects of resveratrol, further highlighting its
      potential future use as a therapeutic agent. This review provides an up-to-date
      discussion on recent advances regarding anti-inflammatory effects of resveratrol,
      mechanisms of action, and its potential for therapeutic use.

PMID- 22587022
TI  - Complete definition of immunological correlates of protection and clearance of
      hepatitis C virus infection: a relevant pending task for vaccine development.
AB  - Hepatitis C virus (HCV) infects approximately 3% of global population. This
      pathogen is one of the main causes of chronic viral hepatitis, cirrhosis, and
      liver cancer, as well as the principal reason for liver transplant in Western
      countries. Therapy against HCV infection is effective in only half of treated
      patients. There is no vaccine available against HCV. Some vaccine candidates have
      reached the clinical trials but several factors, including the incomplete
      definition of immunological correlates of protection and treatment-related
      clearance have slowed down vaccine development. Precisely, the present review
      discusses the state of the art in the establishment of parameters related with
      immunity against HCV. Validity and limitations of the information accumulated
      from chimpanzees and other animal models, analysis of studies in humans infected
      with HCV, and relevance of aspects like type, strength, duration, and specificity
      of immune response related to successful outcome are evaluated in detail.
      Moreover, the immune responses induced in some clinical trials with vaccine
      candidates resemble the theoretical immunological correlates, raising questions
      about the validity of those correlates. When all facts are taken together,
      complete definition of immunological correlates for protection or treatment
      related clearance is an urgent priority. A limited or wrong criterion with
      respect to this relevant matter might cause incorrect vaccine design and
      selection of immunization strategies or erroneous clinical evaluation.

PMID- 22587023
TI  - Measuring geographic access to health care: raster and network-based methods.
AB  - BACKGROUND: Inequalities in geographic access to health care result from the
      configuration of facilities, population distribution, and the transportation
      infrastructure. In recent accessibility studies, the traditional distance measure
      (Euclidean) has been replaced with more plausible measures such as travel
      distance or time. Both network and raster-based methods are often utilized for
      estimating travel time in a Geographic Information System. Therefore, exploring
      the differences in the underlying data models and associated methods and their
      impact on geographic accessibility estimates is warranted. METHODS: We examine
      the assumptions present in population-based travel time models. Conceptual and
      practical differences between raster and network data models are reviewed, along
      with methodological implications for service area estimates. Our case study
      investigates Limited Access Areas defined by Michigan's Certificate of Need (CON)
      Program. Geographic accessibility is calculated by identifying the number of
      people residing more than 30 minutes from an acute care hospital. Both network
      and raster-based methods are implemented and their results are compared. We also
      examine sensitivity to changes in travel speed settings and population
      assignment. RESULTS: In both methods, the areas identified as having limited
      accessibility were similar in their location, configuration, and shape. However,
      the number of people identified as having limited accessibility varied
      substantially between methods. Over all permutations, the raster-based method
      identified more area and people with limited accessibility. The raster-based
      method was more sensitive to travel speed settings, while the network-based
      method was more sensitive to the specific population assignment method employed
      in Michigan. CONCLUSIONS: Differences between the underlying data models help to
      explain the variation in results between raster and network-based methods.
      Considering that the choice of data model/method may substantially alter the
      outcomes of a geographic accessibility analysis, we advise researchers to use
      caution in model selection. For policy, we recommend that Michigan adopt the
      network-based method or reevaluate the travel speed assignment rule in the raster
      based method. Additionally, we recommend that the state revisit the population
      assignment method.

PMID- 22587024
TI  - Persistence of vigilance and flight response behaviour in wild reindeer with
      varying domestic ancestry.
AB  - Knowledge about changes in behavioural traits related to wildness and tameness is
      for most mammals lacking, despite the increased trend of using domestic stock to
      re-establish wild populations into historical ranges. To test for persistence of
      behavioural traits of wild reindeer (Rangifer tarandus L.) exposed to hunting, we
      sampled DNA, vigilance and flight responses in wild reindeer herds with varying
      domestic ancestry. Analyses of 14 DNA microsatellite loci revealed a dichotomous
      main genetic structure reflecting their native origin, with the Rondane reindeer
      genetically different from the others and with least differentiation towards the
      Hardangervidda reindeer. The genetic clustering of the reindeer in Norefjell
      Reinsjofjell, Ottadalen and Forollhogna, together with domestic reindeer,
      supports a predominant domestic origin of these herds. Despite extensive hunting
      in all herds, the behavioural measures indicate increasing vigilance, alert and
      flight responses with increasing genetic dissimilarity with domestic herds.
      Vigilance frequency and time spent vigilant were higher in Rondane compared to
      Hardangervidda, which again were higher than herds with a domestic origin. We
      conclude that previous domestication has preserved a hard wired behavioural trait
      in some reindeer herds exhibiting less fright responses towards humans that
      extensive hunting has, but only slightly, altered. This brings novel and relevant
      knowledge to discussions about genetic diversity of wildlife in general and wild
      reindeer herds in Norway in specific.

PMID- 22587025
TI  - Correlation between molecular signals and bone bonding to titanium implants.
AB  - OBJECTIVES: A better understanding of the biological processes controlling
      osseointegration at the bone-to-implant interface is needed. The aim of this
      study was to examine which are the molecular and biochemical variables that are
      significantly related to osseointegration, using multiple regression analysis.
      MATERIALS AND METHODS: Titanium coins were placed into the tibial cortical bone
      of New Zealand White rabbits and evaluated using pull-out test after 4 and 8
      weeks of healing. Correlations between pull-out and several markers from tissue
      fluid (Lactate dehydrogenase [LDH] and Alkaline phosphatase [ALP] activities and
      total protein content) and peri-implant bone tissue (total protein, RNA and DNA
      content, implant area covered with bone and gene expression of osteoblast,
      osteoclast and inflammation markers) were used to assess the importance of these
      parameters in bone healing and in relation to implant performance. RESULTS: Our
      results showed a negative correlation between the content of DNA, RNA and total
      protein at the peri-implant bone tissue and the pull-out force, indicating that
      as bone matures and implant becomes more osseointegrated, the organic content of
      bone decreases. The negative correlation found between pull-out force and ALP
      activity pointed to a delayed healing in implants with lower pull-out values and
      primary mineralization still ongoing. LDH activity and total protein content in
      the tissue fluid were as well negatively correlated with the pull-out force.
      Finally, a positive correlation was observed between the pull-out force and the
      expression of the osteoblast and the bone resorption markers, being osteocalcin
      and collagen-I the best predictive markers for osseointegration after 4 and 8
      weeks of healing respectively. CONCLUSIONS: These results suggest that the
      evaluation of these markers could be relevant for the assessment of new implant
      surfaces for rapid bone healing and improved implant performance.

PMID- 22587026
TI  - Dental implants from the patients perspective: transition from tooth loss,
      through amputation to implants - negative and positive trajectories.
AB  - AIM: The aim of this study was to explore patients' expectations on and
      experiences from dental implant treatment through deep-interview technique.
      MATERIAL & METHODS: A qualitative study design was chosen and 17 patients were
      interviewed by open-ended questions. All patients in the study had a previous
      history of periodontal disease with, in most cases, many years of treatment. The
      interviews were transcribed; a coding process was used according to qualitative
      conventional content analysis. RESULTS: In the analysis, a core category was
      identified as "Transition from tooth loss, to 'Amputation', and to implants -
      negative and positive trajectories". When the patients faced the fact that it was
      not possible to keep the teeth any longer, a period of fear, shame and denial,
      which also affected their social life negatively followed. After they received
      their implants and the chewing ability and appearance became better, it also
      improved their quality of life. CONCLUSION: Treatment with dental implants
      improved function, enhanced self-esteem, social life and, thus quality of life.
      In clinical practice, information about dental implants and motivational
      strategies are needed during the period before getting dental implants. Follow-up
      is important thereafter, capturing both the pros and cons with implants.

PMID- 22587027
TI  - Inhomogeneities on all scales at a phase transition altered by disorder.
AB  - We have done a finite-size scaling study of a continuous phase transition altered
      by the quenched bond disorder, investigating systems at quasicritical
      temperatures of each disorder realization by using the equilibriumlike invaded
      cluster algorithm. Our results indicate that in order to access the thermal
      critical exponent y(tau), it is necessary to average the free energy at
      quasicritical temperatures of each disorder configuration. Despite the thermal
      fluctuations on the scale of the system at the transition point, we find that
      spatial inhomogeneities form in the system and become more pronounced as the size
      of the system increases. This leads to different exponents describing rescaling
      of the fluctuations of observables in disorder and thermodynamic ensembles.

PMID- 22587028
TI  - Phenomenology of aging in the Kardar-Parisi-Zhang equation.
AB  - We study aging during surface growth processes described by the one-dimensional
      Kardar-Parisi-Zhang equation. Starting from a flat initial state, the systems
      undergo simple aging in both correlators and linear responses, and its dynamical
      scaling is characterized by the aging exponents a=-1/3, b=-2/3,
      lambda(C)=lambda(R)=1, and z=3/2. The form of the autoresponse scaling function
      is well described by the recently constructed logarithmic extension of local
      scale invariance.

PMID- 22587029
TI  - Jammed spheres: Minkowski tensors reveal onset of local crystallinity.
AB  - The local structure of disordered jammed packings of monodisperse spheres without
      friction, generated by the Lubachevsky-Stillinger algorithm, is studied for
      packing fractions above and below 64%. The structural similarity of the particle
      environments to fcc or hcp crystalline packings (local crystallinity) is
      quantified by order metrics based on rank-four Minkowski tensors. We find a
      critical packing fraction phi(c)~0.649, distinctly higher than previously
      reported values for the contested random close packing limit. At phi(c), the
      probability of finding local crystalline configurations first becomes finite and,
      for larger packing fractions, increases by several orders of magnitude. This
      provides quantitative evidence of an abrupt onset of local crystallinity at
      phi(c). We demonstrate that the identification of local crystallinity by the
      frequently used local bond-orientational order metric q(6) produces false
      positives and thus conceals the abrupt onset of local crystallinity. Since the
      critical packing fraction is significantly above results from mean-field analysis
      of the mechanical contacts for frictionless spheres, it is suggested that dynamic
      arrest due to isostaticity and the alleged geometric phase transition in the
      Edwards framework may be disconnected phenomena.

PMID- 22587030
TI  - 4He crystals in superfluid under zero gravity.
AB  - The response of 4He crystals to the rapid reduction of gravity down to
      practically zero in a superfluid was investigated visually, utilizing the
      parabolic flight of a jet plane. At a high temperature of 1.6 K, the shape of 4He
      crystals in the bcc phase did not change with a reduction of gravity during a
      parabolic period of 20 s, due to the low crystallization rate. At lower
      temperatures, such as 0.63 K, where the crystallization rate is sufficiently
      high, the shape of 4He crystals in the hcp phase changed significantly, relaxing
      to a quasiequilibrium shape under zero gravity, where the c facet became enlarged
      and the a facet emerged on the surface. The crystal did not detach from the
      sample cell wall at any time because the adhesive force manifested as partial
      wetting to the wall was sufficiently strong. Some crystals removed from the wall
      by an acoustic wave pulse were found to float and drift in the superfluid for
      approximately 4.2 s under zero gravity, although most of them were quickly
      reattached to the wall.

PMID- 22587031
TI  - Glassy dynamics in relaxation of soft-mode turbulence.
AB  - The autocorrelation function of pattern fluctuation is used to study soft-mode
      turbulence (SMT), a spatiotemporal chaos observed in homeotropic nematics. We
      show that relaxation near the electroconvection threshold deviates from the
      exponential. To describe this relaxation, we propose a compressed exponential
      appearing in dynamics of glass-forming liquids. Our findings suggest that
      coherent motion contributes to SMT dynamics. We also confirmed that
      characteristic time is inversely proportional to electroconvection's control
      parameter.

PMID- 22587032
TI  - Holographic entanglement entropy in Suzuki-Trotter decomposition of spin systems.
AB  - In quantum spin chains at criticality, two types of scaling for the entanglement
      entropy exist: one comes from conformal field theory (CFT), and the other is for
      entanglement support of matrix product state (MPS) approximation. On the other
      hand, the quantum spin-chain models can be mapped onto two-dimensional (2D)
      classical ones by the Suzuki-Trotter decomposition. Motivated by the scaling and
      the mapping, we introduce information entropy for 2D classical spin
      configurations as well as a spectrum, and examine their basic properties in the
      Ising and the three-state Potts models on the square lattice. They are defined by
      the singular values of the reduced density matrix for a Monte Carlo snapshot. We
      find scaling relations of the entropy compatible with the CFT and the MPS
      results. Thus, we propose that the entropy is a kind of "holographic"
      entanglement entropy. At T(c), the spin configuration is fractal, and various
      sizes of ordered clusters coexist. Then, the singular values automatically
      decompose the original snapshot into a set of images with different length
      scales, respectively. This is the origin of the scaling. In contrast to the MPS
      scaling, long-range spin correlation can be described by only few singular
      values. Furthermore, the spectrum, which is a set of logarithms of the singular
      values, also seems to be a holographic entanglement spectrum. We find multiple
      gaps in the spectrum, and in contrast to the topological phases, the low-lying
      levels below the gap represent spontaneous symmetry breaking. These contrasts are
      strong evidence of the dual nature of the holography. Based on these
      observations, we discuss the amount of information contained in one snapshot.

PMID- 22587033
TI  - Validity of nonequilibrium work relations for the rapidly expanding quantum
      piston.
AB  - Recent work by Teifel and Mahler [Eur. Phys. J. B 75, 275 (2010)] raises
      legitimate concerns regarding the validity of quantum nonequilibrium work
      relations in processes involving moving hard walls. We study this issue in the
      context of the rapidly expanding one-dimensional quantum piston. Utilizing exact
      solutions of the time-dependent Schrodinger equation, we find that the evolution
      of the wave function can be decomposed into static and dynamic components, which
      have simple semiclassical interpretations in terms of particle-piston collisions.
      We show that nonequilibrium work relations remain valid at any finite piston
      speed, provided both components are included, and we study explicitly the work
      distribution for this model system.

PMID- 22587034
TI  - Bohman-Frieze-Wormald model on the lattice, yielding a discontinuous percolation
      transition.
AB  - The BFW model introduced by Bohman, Frieze, and Wormald [Random Struct.
      Algorithms, 25, 432 (2004)], and recently investigated in the framework of
      discontinuous percolation by Chen and D'Souza [Phys. Rev. Lett. 106, 115701
      (2011)], is studied on the square and simple-cubic lattices. In two and three
      dimensions, we find numerical evidence for a strongly discontinuous transition.
      In two dimensions, the clusters at the threshold are compact with a fractal
      surface of fractal dimension d(f)=1.49+/-0.02. On the simple-cubic lattice,
      distinct jumps in the size of the largest cluster are observed. We proceed to
      analyze the tree-like version of the model, where only merging bonds are sampled,
      for dimension two to seven. The transition is again discontinuous in any
      considered dimension. Finally, the dependence of the cluster-size distribution at
      the threshold on the spatial dimension is also investigated.

PMID- 22587035
TI  - Continuous transition of social efficiencies in the stochastic-strategy minority
      game.
AB  - We show that in a variant of the minority game problem, the agents can reach a
      state of maximum social efficiency, where the fluctuation between the two choices
      is minimum, by following a simple stochastic strategy. By imagining a social
      scenario where the agents can only guess about the number of excess people in the
      majority, we show that as long as the guessed value is sufficiently close to the
      reality, the system can reach a state of full efficiency or minimum fluctuation.
      A continuous transition to less efficient condition is observed when the guessed
      value becomes worse. Hence, people can optimize their guess for excess population
      to optimize the period of being in the majority state. We also consider the
      situation where a finite fraction of agents always decide completely randomly
      (random trader) as opposed to the rest of the population who follow a certain
      strategy (chartist). For a single random trader the system becomes fully
      efficient with majority-minority crossover occurring every 2 days on average. For
      just two random traders, all the agents have equal gain with arbitrarily small
      fluctuations.

PMID- 22587036
TI  - Nonstationary dynamics of the Alessandro-Beatrice-Bertotti-Montorsi model.
AB  - We obtain an exact solution for the motion of a particle driven by a spring in a
      Brownian random-force landscape, the Alessandro-Beatrice-Bertotti-Montorsi (ABBM)
      model. Many experiments on quasistatic driving of elastic interfaces (Barkhausen
      noise in magnets, earthquake statistics, shear dynamics of granular matter)
      exhibit the same universal behavior as this model. It also appears as a limit in
      the field theory of elastic manifolds. Here we discuss predictions of the ABBM
      model for monotonous, but otherwise arbitrary, time-dependent driving. Our main
      result is an explicit formula for the generating functional of particle
      velocities and positions. We apply this to derive the particle-velocity
      distribution following a quench in the driving velocity. We also obtain the joint
      avalanche size and duration distribution and the mean avalanche shape following a
      jump in the position of the confining spring. Such nonstationary driving is easy
      to realize in experiments, and provides a way to test the ABBM model beyond the
      stationary, quasistatic regime. We study extensions to two elastically coupled
      layers, and to an elastic interface of internal dimension d, in the Brownian
      force landscape. The effective action of the field theory is equal to the action,
      up to one-loop corrections obtained exactly from a functional determinant. This
      provides a connection to renormalization-group methods.

PMID- 22587037
TI  - Singular response of bistable systems driven by telegraph noise.
AB  - We show that weak periodic driving can exponentially strongly change the rate of
      escape from a potential well of a system driven by telegraph noise. The analysis
      refers to an overdamped system, where escape requires that the noise amplitude
      theta exceed a critical value theta(c). For theta close to theta(c), the exponent
      of the escape rate displays a nonanalytic dependence on the amplitude of an
      additional low-frequency modulation. This leads to giant nonlinearity of the
      response of a bistable system to periodic modulation. Also studied is the linear
      response to periodic modulation far from theta(c). We analyze the scaling of the
      logarithm of the escape rate with the distance to the saddle-node and pitchfork
      bifurcation points. The analytical results are in excellent agreement with
      numerical simulations.

PMID- 22587038
TI  - Small-network approximations for geometrically frustrated Ising systems.
AB  - The study of frustrated spin systems often requires time-consuming numerical
      simulations. As the simplest approach, the classical Ising model is often used to
      investigate the thermodynamic behavior of such systems. Exploiting the small
      correlation lengths in frustrated Ising systems, we develop a method for
      obtaining first approximations to the energetic properties of frustrated two
      dimensional Ising systems using small networks of less than 30 spins. These small
      networks allow much faster numerical simulations, and more importantly,
      analytical evaluations of their properties are numerically tractable. We choose
      Ising systems on the triangular lattice, the kagome lattice, and the triangular
      kagome lattice as prototype systems and find small systems that can serve as good
      approximations to these prototype systems. Through comparisons between the
      properties of extended models and small systems, we develop a set of criteria for
      constructing small networks to approximate general infinite two-dimensional
      frustrated Ising systems. This method of using small networks provides a
      different and efficient way to obtain a first approximation to the properties of
      frustrated spin systems.

PMID- 22587039
TI  - Out-of-equilibrium relaxation of the thermal Casimir effect in a model
      polarizable material.
AB  - Relaxation of the thermal Casimir or van der Waals force (the high temperature
      limit of the Casimir force) for a model dielectric medium is investigated. We
      start with a model of interacting polarization fields with a dynamics that leads
      to a frequency dependent dielectric constant of the Debye form. In the static
      limit, the usual zero frequency Matsubara mode component of the Casimir force is
      recovered. We then consider the out-of-equilibrium relaxation of the van der
      Waals force to its equilibrium value when two initially uncorrelated dielectric
      bodies are brought into sudden proximity. For the interaction between dielectric
      slabs, it is found that the spatial dependence of the out-of-equilibrium force is
      the same as the equilibrium one, but it has a time dependent amplitude, or
      Hamaker coefficient, which increases in time to its equilibrium value. The final
      relaxation of the force to its equilibrium value is exponential in systems with a
      single or finite number of polarization field relaxation times. However, in
      systems, such as those described by the Havriliak-Negami dielectric constant with
      a broad distribution of relaxation times, we observe a much slower power law
      decay to the equilibrium value.

PMID- 22587040
TI  - Energy transport in closed quantum systems.
AB  - We examine energy transport in an ensemble of closed quantum systems driven by
      stochastic perturbations. One can show that the probability and energy fluxes can
      be described in terms of quantum advection modes (QAMs) associated with the off
      diagonal elements of the density matrix. These QAMs play the role of Landauer
      channels in a system with discrete energy spectrum and the eigenfunctions that
      cannot be described as plane waves. In order to determine the type of
      correlations that exist between the direction and magnitudes of each QAM and the
      average direction of energy and probability fluxes we have numerically solved the
      time-dependent Schrodinger equation describing a single particle trapped in a
      parabolic potential well which is perturbed by stochastic ripples. The ripples
      serve as a localized energy source and are offset to one side of the potential
      well. As the result a nonzero net energy flux flows from one part of the
      potential well to another across the symmetry center of the potential. We find
      that some modes exhibit positive correlation with the direction of the energy
      flow. Other modes, that carry a smaller energy per unit of the probability flux,
      anticorrelate with the energy flow and thus provide a backflow of the
      probability. The overall picture of energy transport that emerges from our
      results is very different from the conventional one based on a system with
      continuous energy spectrum.

PMID- 22587041
TI  - Quantum-trajectory approach to the stochastic thermodynamics of a forced harmonic
      oscillator.
AB  - I formulate a quantum stochastic thermodynamics for the quantum trajectories of a
      continuously monitored forced harmonic oscillator coupled to a thermal reservoir.
      Consistent trajectory-dependent definitions are introduced for work, heat, and
      entropy, through engineering the thermal reservoir from a sequence of two-level
      systems. Within this formalism the connection between irreversibility and entropy
      production is analyzed and confirmed by proving a detailed fluctuation theorem
      for quantum trajectories. Finally, possible experimental verifications are
      discussed.

PMID- 22587042
TI  - Flooding transition in the topography of toppling surfaces of stochastic and
      rotational sandpile models.
AB  - A continuous phase transition occurs in the topography of toppling surfaces of
      stochastic and rotational sandpile models when they are flooded with liquid, say
      water. The toppling surfaces are extracted from the sandpile avalanches that
      appear due to sudden burst of toppling activity in the steady state of these
      sandpile models. Though a wide distribution of critical flooding heights exists,
      a critical point is defined by merging the flooding thresholds of all the
      toppling surfaces. The criticality of the transition is characterized by power
      law distribution of island area in the critical regime. A finite size scaling
      theory is developed and verified by calculating several new critical exponents.
      The flooding transition is found to be an interesting phase transition and does
      not belong to the percolation universality class. The universality class of this
      transition is found to depend on the degree of self-affinity of the toppling
      surfaces characterized by the Hurst exponent H and the fractal dimension D(f) of
      critical spanning islands. The toppling surfaces of different stochastic sandpile
      models are found to have a single Hurst exponent, whereas those of different
      rotational sandpile models have another Hurst exponent. As a consequence, the
      universality class of different sandpile models remains preserved within the same
      symmetry of the models.

PMID- 22587043
TI  - Nonequilibrium fluctuations in a driven stochastic Lorentz gas.
AB  - We study the stationary state of a one-dimensional kinetic model where a probe
      particle is driven by an external field E and collides, elastically or
      inelastically, with a bath of particles at temperature T. We focus on the
      stationary distribution of the velocity of the particle, and of two estimates of
      the total entropy production Deltas(tot). One is the entropy production of the
      medium Deltas(m), which is equal to the energy exchanged with the scatterers,
      divided by a parameter theta, coinciding with the particle temperature at E=0.
      The other is the work W done by the external field, again rescaled by theta. At
      small E, a good collapse of the two distributions is found: in this case, the two
      quantities also verify the fluctuation relation (FR), indicating that both are
      good approximations of Deltas(tot). Differently, for large values of E, the
      fluctuations of W violate the FR, while Deltas(m) still verifies it.

PMID- 22587044
TI  - Geometrical exponents of contour loops on synthetic multifractal rough surfaces:
      multiplicative hierarchical cascade p model.
AB  - In this paper, we study many geometrical properties of contour loops to
      characterize the morphology of synthetic multifractal rough surfaces, which are
      generated by multiplicative hierarchical cascading processes. To this end, two
      different classes of multifractal rough surfaces are numerically simulated. As
      the first group, singular measure multifractal rough surfaces are generated by
      using the p model. The smoothened multifractal rough surface then is simulated by
      convolving the first group with a so-called Hurst exponent, H*. The generalized
      multifractal dimension of isoheight lines (contours), D(q), correlation exponent
      of contours, x(l), cumulative distributions of areas, xi, and perimeters, eta,
      are calculated for both synthetic multifractal rough surfaces. Our results show
      that for both mentioned classes, hyperscaling relations for contour loops are the
      same as that of monofractal systems. In contrast to singular measure multifractal
      rough surfaces, H* plays a leading role in smoothened multifractal rough
      surfaces. All computed geometrical exponents for the first class depend not only
      on its Hurst exponent but also on the set of p values. But in spite of
      multifractal nature of smoothened surfaces (second class), the corresponding
      geometrical exponents are controlled by H*, the same as what happens for
      monofractal rough surfaces.

PMID- 22587045
TI  - Multiparticle quantum Szilard engine with optimal cycles assisted by a Maxwell's
      demon.
AB  - We present a complete-quantum description of a multiparticle Szilard engine that
      consists of a working substance and a Maxwell's demon. The demon is modeled as a
      multilevel quantum system with specific quantum control, and the working
      substance consists of identical particles obeying Bose-Einstein or Fermi-Dirac
      statistics. In this description, a reversible scheme to erase the demon's memory
      by a lower-temperature heat bath is used. We demonstrate that (1) the quantum
      control of the demon can be optimized for a single-particle Szilard engine so
      that the efficiency of the demon-assisted thermodynamic cycle could reach the
      Carnot cycle's efficiency and (2) the low-temperature behavior of the working
      substance is very sensitive to the quantum statistics of the particles and the
      insertion position of the partition.

PMID- 22587046
TI  - Lower and upper bounds on the fidelity susceptibility.
AB  - We derive upper and lower bounds on the fidelity susceptibility in terms of
      macroscopic thermodynamical quantities, such as the susceptibilities and thermal
      average values. The quality of the bounds is checked against the exact
      expressions for a single spin in an external magnetic field. Their usefulness is
      illustrated by two examples of many-particle models which are exactly solved in
      the thermodynamic limit: the Dicke superradiance model and the single-impurity
      Kondo model. It is shown that, when divergent behavior is considered, the
      fidelity susceptibility and the thermodynamic susceptibility are equivalent for a
      large class of models exhibiting critical behavior.

PMID- 22587047
TI  - Irreversibilities and efficiency at maximum power of heat engines: the
      illustrative case of a thermoelectric generator.
AB  - Energy conversion efficiency at maximum output power, which embodies the
      essential characteristics of heat engines, is the main focus of the present work.
      The so-called Curzon and Ahlborn efficiency eta(CA) is commonly believed to be an
      absolute reference for real heat engines; however, a different but general
      expression for the case of stochastic heat engines, eta(SS), was recently found
      and then extended to low-dissipation engines. The discrepancy between eta(CA) and
      eta(SS) is here analyzed considering different irreversibility sources of heat
      engines, of both internal and external types. To this end, we choose a
      thermoelectric generator operating in the strong-coupling regime as a physical
      system to qualitatively and quantitatively study the impact of the nature of
      irreversibility on the efficiency at maximum output power. In the limit of pure
      external dissipation, we obtain eta(CA), while eta(SS) corresponds to the case of
      pure internal dissipation. A continuous transition between from one extreme to
      the other, which may be operated by tuning the different sources of
      irreversibility, also is evidenced.

PMID- 22587048
TI  - Stochastically driven single-level quantum dot: a nanoscale finite-time
      thermodynamic machine and its various operational modes.
AB  - We describe a single-level quantum dot in contact with two leads as a nanoscale
      finite-time thermodynamic machine. The dot is driven by an external stochastic
      force that switches its energy between two values. In the isothermal regime, it
      can operate as a rechargeable battery by generating an electric current against
      the applied bias in response to the stochastic driving and then redelivering work
      in the reverse cycle. This behavior is reminiscent of the Parrondo paradox. If
      there is a thermal gradient the device can function as a work-generating thermal
      engine or as a refrigerator that extracts heat from the cold reservoir via the
      work input of the stochastic driving. The efficiency of the machine at maximum
      power output is investigated for each mode of operation, and universal features
      are identified.

PMID- 22587049
TI  - Propagation on networks: an exact alternative perspective.
AB  - By generating the specifics of a network structure only when needed (on-the-fly),
      we derive a simple stochastic process that exactly models the time evolution of
      susceptible-infectious dynamics on finite-size networks. The small number of
      dynamical variables of this birth-death Markov process greatly simplifies
      analytical calculations. We show how a dual analytical description, treating
      large scale epidemics with a Gaussian approximation and small outbreaks with a
      branching process, provides an accurate approximation of the distribution even
      for rather small networks. The approach also offers important computational
      advantages and generalizes to a vast class of systems.

PMID- 22587050
TI  - Dynamic mean-field and cavity methods for diluted Ising systems.
AB  - We compare dynamic mean-field and dynamic cavity methods to describe the
      stationary states of dilute kinetic Ising models. We compute dynamic mean-field
      theory by expanding in interaction strength to third order, and we compare to the
      exact dynamic mean-field theory for fully asymmetric networks. We show that in
      diluted networks, the dynamic cavity method generally predicts magnetizations of
      individual spins better than both first-order ("naive") and second-order ("TAP")
      dynamic mean-field theory.

PMID- 22587051
TI  - Fractional Brownian motion and the critical dynamics of zipping polymers.
AB  - We consider two complementary polymer strands of length L attached by a common
      end monomer. The two strands bind through complementary monomers and at low
      temperatures form a double-stranded conformation (zipping), while at high
      temperature they dissociate (unzipping). This is a simple model of DNA (or RNA)
      hairpin formation. Here we investigate the dynamics of the strands at the
      equilibrium critical temperature T=T(c) using Monte Carlo Rouse dynamics. We find
      that the dynamics is anomalous, with a characteristic time scaling as
      tau~L(2.26(2)), exceeding the Rouse time ~L(2.18). We investigate the probability
      distribution function, velocity autocorrelation function, survival probability,
      and boundary behavior of the underlying stochastic process. These quantities
      scale as expected from a fractional Brownian motion with a Hurst exponent
      H=0.44(1). We discuss similarities to and differences from unbiased polymer
      translocation.

PMID- 22587052
TI  - Testing a model with an extended O(2) symmetry in two and three dimensions.
AB  - We investigate a model with an extended O(2) symmetry in two and three
      dimensions, using the combination of extensive Monte Carlo simulations and the
      finite-size scaling. On this basis, we establish rich phase diagrams, which are
      constituted by O(2) critical lines. From various prospectives, the ordered states
      on the phase diagrams can be classified into intraspecies and interspecies
      correlated phases, quasi-long-range and long-range ordered phases, or
      ferromagnetic and antiferromagnetic phases. We furthermore show that the
      dimensionality effect acts on not only the ordering property, but also the
      topological structure of the phase diagram.

PMID- 22587053
TI  - Relaxation in finite and isolated classical systems: an extension of Onsager's
      regression hypothesis.
AB  - In order to derive the reciprocity relations, Onsager formulated a relation
      between thermal equilibrium fluctuations and relaxation widely known as
      regression hypothesis. It is shown in the present work how such a relation can be
      extended to finite and isolated classical systems. This extension is derived from
      the fluctuation-dissipation theorem for the microcanonical ensemble. The results
      are exemplified with a nonintegrable system in order to motivate possible
      applications to dynamical systems and statistical mechanics of finite systems.

PMID- 22587054
TI  - Absorbing states of zero-temperature Glauber dynamics in random networks.
AB  - We study zero-temperature Glauber dynamics for Ising-like spin variable models in
      quenched random networks with random zero-magnetization initial conditions. In
      particular, we focus on the absorbing states of finite systems. While it has
      quite often been observed that Glauber dynamics lets the system be stuck into an
      absorbing state distinct from its ground state in the thermodynamic limit, very
      little is known about the likelihood of each absorbing state. In order to explore
      the variety of absorbing states, we investigate the probability distribution
      profile of the active link density after saturation as the system size N and (k)
      vary. As a result, we find that the distribution of absorbing states can be split
      into two self-averaging peaks whose positions are determined by (k), one slightly
      above the ground state and the other farther away. Moreover, we suggest that the
      latter peak accounts for a nonvanishing portion of samples when N goes to
      infinity while (k) stays fixed. Finally, we discuss the possible implications of
      our results on opinion dynamics models.

PMID- 22587055
TI  - Reaction-diffusion process driven by a localized source: first-passage
      properties.
AB  - We study a reaction-diffusion process that involves two species of atoms,
      immobile and diffusing. We start with only immobile atoms uniformly distributed
      throughout the entire space. Diffusing atoms are injected at the origin by a
      source that is turned on at time t=0. When a diffusing atom collides with an
      immobile atom, the two atoms form an immobile stable molecule. The region
      occupied by molecules is asymptotically spherical with radius growing as t(1/d)
      in d>=2 dimensions. We investigate the survival probability that a diffusing atom
      has not become a part of a molecule during the time interval t after its
      injection. We show that, asymptotically, the survival probability (i) saturates
      in one dimension, (ii) vanishes algebraically with time in two dimensions (with
      exponent being a function of the dimensionless flux and determined as a zero of a
      confluent hypergeometric function), and (iii) exhibits a stretched exponential
      decay in three dimensions.

PMID- 22587056
TI  - Ripples in a string coupled to Glauber spins.
AB  - Each oscillator in a linear chain (a string) interacts with a local Ising spin in
      contact with a thermal bath. These spins evolve according to Glauber dynamics.
      Below a critical temperature, there appears an equilibrium, time-independent,
      rippled state in the string that is accompanied by a nonzero spin polarization.
      On the other hand, the system is shown to form "metastable," nonequilibrium long
      lived ripples in the string for slow spin relaxation. The system vibrates rapidly
      about these quasistationary states, which can be described as snapshots of a
      coarse-grained stroboscopic map. For moderate observation times, ripples are
      observed irrespective of the final thermodynamically stable state (rippled or
      not). Interestingly, the system can be considered as a "minimal" model to
      understand rippling in clamped graphene sheets.

PMID- 22587057
TI  - Mean-field-like behavior of the generalized voter-model-class kinetic Ising
      model.
AB  - We analyze a kinetic Ising model with suppressed bulk noise, which is a prominent
      representative of the generalized voter model phase transition. On the one hand,
      we discuss the model in the context of social systems and opinion formation in
      the presence of a tunable social temperature. On the other hand, we characterize
      the abrupt phase transition. The system shows nonequilibrium dynamics in the
      presence of absorbing states. We slightly change the system to get a stationary
      state model variant exhibiting the same kind of phase transition. Using a Fokker
      Planck description and comparing to mean-field calculations, we investigate the
      phase transition, finite-size effects, and the effect of the absorbing states
      resulting in a dynamic slowing down.

PMID- 22587058
TI  - Thermodynamic interpretation of soft glassy rheology models.
AB  - Mesoscopic models play an important role in our understanding of the deformation
      and flow of amorphous materials. One such description, based on the shear
      transformation zone theory, has recently been reformulated within a
      nonequilibrium thermodynamics framework and found to be consistent with it. We
      show here that a similar interpretation can be made for the soft glassy rheology
      (SGR) model. Conceptually this means that the "noise temperature" x, proposed
      phenomenologically in the SGR model to control the dynamics of a set of slow
      mesoscopic degrees of freedom, can consistently be interpreted as their actual
      thermodynamic temperature. (Because such modes are slow to equilibrate, this
      generally does not coincide with the temperature of the fast degrees of freedom
      and/or heat bath.) If one chooses to make this interpretation, the thermodynamic
      framework significantly constrains extensions of the SGR approach to models in
      which x is a dynamical variable. We assess in this light some such extensions
      recently proposed in the context of shear banding.

PMID- 22587059
TI  - Entropic dynamical hysteresis in a driven system.
AB  - We show that the application of a time periodic field driving a Brownian particle
      between the two lobes of a two-dimensional bilobal enclosure results in a
      hysteresis loop in the variation of integrated probability of residence of the
      particle as a function of the field. The confinement of the particle is
      characterized by symmetry breaking of the hysteresis loop, and the area of the
      loop exhibits a turnover with variation of frequency of the field. This dynamical
      hysteresis is geometry controlled, entropic in nature, and amenable to
      theoretical analysis with a two-state model.

PMID- 22587060
TI  - Entropy production and Kullback-Leibler divergence between stationary
      trajectories of discrete systems.
AB  - The irreversibility of a stationary time series can be quantified using the
      Kullback-Leibler divergence (KLD) between the probability of observing the series
      and the probability of observing the time-reversed series. Moreover, this KLD is
      a tool to estimate entropy production from stationary trajectories since it gives
      a lower bound to the entropy production of the physical process generating the
      series. In this paper we introduce analytical and numerical techniques to
      estimate the KLD between time series generated by several stochastic dynamics
      with a finite number of states. We examine the accuracy of our estimators for a
      specific example, a discrete flashing ratchet, and investigate how close the KLD
      is to the entropy production depending on the number of degrees of freedom of the
      system that are sampled in the trajectories.

PMID- 22587061
TI  - Poisson-Helmholtz-Boltzmann model of the electric double layer: analysis of
      monovalent ionic mixtures.
AB  - In the classical mean-field description of the electric double layer, known as
      the Poisson-Boltzmann model, ions interact exclusively through their Coulomb
      potential. Ion specificity can arise through solvent-mediated, nonelectrostatic
      interactions between ions. We employ the Yukawa pair potential to model the
      presence of nonelectrostatic interactions. The combination of Yukawa and Coulomb
      potential on the mean-field level leads to the Poisson-Helmholtz-Boltzmann model,
      which employs two auxiliary potentials: one electrostatic and the other
      nonelectrostatic. In the present work we apply the Poisson-Helmholtz-Boltzmann
      model to ionic mixtures, consisting of monovalent cations and anions that exhibit
      different Yukawa interaction strengths. As a specific example we consider a
      single charged surface in contact with a symmetric monovalent electrolyte. From
      the minimization of the mean-field free energy we derive the Poisson-Boltzmann
      and Helmholtz-Boltzmann equations. These nonlinear equations can be solved
      analytically in the weak perturbation limit. This together with numerical
      solutions in the nonlinear regime suggests an intricate interplay between
      electrostatic and nonelectrostatic interactions. The structure and free energy of
      the electric double layer depends sensitively on the Yukawa interaction strengths
      between the different ion types and on the nonelectrostatic interactions of the
      mobile ions with the surface.

PMID- 22587062
TI  - Comparison of complete scaling and a field-theoretic treatment of asymmetric
      fluid criticality.
AB  - We investigate the connection between the theory of complete scaling and a field
      theoretic (FT) treatment of asymmetric fluid criticality. To facilitate the
      comparison, we develop an equation of state from a simplified form of the
      complete scaling transformations and systematically compare this equation of
      state with the equation of state generated by a FT treatment of an asymmetric
      Landau-Ginzburg-Wilson Hamiltonian. We find, with care in interpretation, that
      these two approaches may be read as equivalent up to terms involving an
      independent higher-order asymmetric correction-to-scaling exponent.

PMID- 22587063
TI  - Subdiffusive master equation with space-dependent anomalous exponent and
      structural instability.
AB  - We derive the fractional master equation with space-dependent anomalous exponent.
      We analyze the asymptotic behavior of the corresponding lattice model both
      analytically and by Monte Carlo simulation. We show that the subdiffusive
      fractional equations with constant anomalous exponent MU in a bounded domain
      [0,L] are not structurally stable with respect to the nonhomogeneous variations
      of parameter MU. In particular, the Gibbs-Boltzmann distribution is no longer the
      stationary solution of the fractional Fokker-Planck equation whatever the space
      variation of the exponent might be. We analyze the random distribution of MU in
      space and find that in the long-time limit, the probability distribution is
      highly intermediate in space and the behavior is completely dominated by very
      unlikely events. We show that subdiffusive fractional equations with the
      nonuniform random distribution of anomalous exponent is an illustration of a
      "Black Swan," the low probability event of the small value of the anomalous
      exponent that completely dominates the long-time behavior of subdiffusive
      systems.

PMID- 22587064
TI  - Inverse freezing in the Ghatak-Sherrington model with a random field.
AB  - The present work studies the Ghatak-Sherrington (GS) model in the presence of a
      magnetic random field (RF). Previous results obtained from the GS model without a
      RF suggest that disorder and frustration are the key ingredients to produce
      spontaneous inverse freezing (IF). However, in this model, the effects of
      disorder and frustration always appear combined. In that sense, the introduction
      of RF allows us to study the IF under the effects of a disorder which is not a
      source of frustration. The problem is solved within the one step replica symmetry
      approximation. The results show that the first order transition between the spin
      glass and the paramagnetic phases, which is related to the IF for a certain range
      of crystal field D, is gradually suppressed when the RF is increased.

PMID- 22587065
TI  - Predictability of extreme events in a nonlinear stochastic-dynamical model.
AB  - The objective of this work is to evaluate the potential of reduced order models
      to reproduce the extreme event and predictability characteristics of higher
      dimensional dynamical systems. A nonlinear toy model is used which contains key
      features of comprehensive climate models. First, we demonstrate that the
      systematic stochastic mode reduction strategy leads to a reduced order model with
      the same extreme value characteristics as the full dynamical models for a wide
      range of time-scale separations. Second, we find that extreme events in this
      model follow a generalized Pareto distribution with a negative shape parameter;
      thus extreme events are bounded in this model. Third, we show that a precursor
      approach has good forecast skill for extreme events. We then find that the
      reduced stochastic models capture the predictive skill of extreme events of the
      full dynamical models well. Consistent with previous studies we also find that
      the larger the extreme events, the better predictable they are. Our results
      suggest that systematically derived reduced order models have the potential to be
      used for the modeling and statistical prediction of weather- and climate-related
      extreme events and, possibly, in other areas of science and engineering too.

PMID- 22587066
TI  - Infinite family of second-law-like inequalities.
AB  - The probability distribution function for an out of equilibrium system may
      sometimes be approximated by a physically motivated "trial" distribution. A
      particularly interesting case is when a driven system (e.g., active matter) is
      approximated by a thermodynamic one. We show here that every set of trial
      distributions yields an inequality playing the role of a generalization of the
      second law. The better the approximation is, the more constraining the inequality
      becomes: this suggests a criterion for its accuracy, as well as an optimization
      procedure that may be implemented numerically and even experimentally. The
      fluctuation relation behind this inequality, a natural and practical extension of
      the Hatano-Sasa theorem, does not rely on the a priori knowledge of the
      stationary probability distribution.

PMID- 22587067
TI  - Optimal estimates of the diffusion coefficient of a single Brownian trajectory.
AB  - Modern developments in microscopy and image processing are revolutionizing areas
      of physics, chemistry, and biology as nanoscale objects can be tracked with
      unprecedented accuracy. The goal of single-particle tracking is to determine the
      interaction between the particle and its environment. The price paid for having a
      direct visualization of a single particle is a consequent lack of statistics.
      Here we address the optimal way to extract diffusion constants from single
      trajectories for pure Brownian motion. It is shown that the maximum likelihood
      estimator is much more efficient than the commonly used least-squares estimate.
      Furthermore, we investigate the effect of disorder on the distribution of
      estimated diffusion constants and show that it increases the probability of
      observing estimates much smaller than the true (average) value.

PMID- 22587068
TI  - Behavior of magnetic currents in anisotropic Heisenberg spin chains out of
      equilibrium.
AB  - The behavior of the magnetic currents in one-dimensional Heisenberg XXZ spin
      chains kept out of equilibrium by boundary driving fields is investigated. In
      particular, the dependence of the spin currents on the anisotropy parameter Delta
      and on the boundary fields is studied both analytically and numerically in the
      framework of the Lindblad master equation formalism. We show that the spin
      current can be maximized with appropriate choices of the boundary fields, and for
      odd system sizes, N, we demonstrate the existence of additional symmetries that
      cause the current to be an odd function of Delta. From direct numerical
      integrations of the quantum master equation, we find that for an arbitrary N the
      current J(z)(N) vanishes for Delta=0, while for Delta negative it alternates its
      sign with the system size. In the gapless critical region |Delta|<1, the scaling
      of the current is shown to be J(z)(N)~1/N while in the gapped region |Delta|>1 we
      find that J(z)(N)~exp(-alphaN). A simple mean-field approach, which predicts
      rather well the values of J(z)(N) for the gapped region and the values of the
      absolute current maxima in the critical region, is developed. The existence of
      two different stationary solutions for the mean-field density matrix in the whole
      parameter range is also demonstrated.

PMID- 22587069
TI  - Operator solutions for fractional Fokker-Planck equations.
AB  - We obtain exact results for fractional equations of Fokker-Planck type using the
      evolution operator method. We employ exact forms of one-sided Levy stable
      distributions to generate a set of self-reproducing solutions. Explicit cases are
      reported and studied for various fractional order of derivatives, different
      initial conditions, and for different versions of Fokker-Planck operators.

PMID- 22587070
TI  - Restoring the three-dimensional correlation function and structure factor from
      two-dimensional data.
AB  - In uniform and isotropic systems the three-dimensional pair distribution function
      and the structure factor can be restored from two-dimensional observations of the
      sliced volume with finite thickness without scanning along the third dimension.
      By numerically simulating such observations of a known system, it is explicitly
      shown that proposed formulas for such restorations are applicable, at least when
      the thickness of the sliced volume is smaller than or comparable to the mean
      distance between particles. It is also pointed out that one cannot simply guess
      the behavior of the long-wavelength limit of the three-dimensional structure
      factor from the two-dimensional observation: Even when the (true) three
      dimensional structure factor vanishes, the observed two-dimensional structure
      factor goes to a finite value which depends on the thickness. The correct
      behavior of the three-dimensional structure factor is given by the restoration
      formula.

PMID- 22587071
TI  - Crossover in growth laws for phase-separating binary fluids: molecular dynamics
      simulations.
AB  - Pattern and dynamics during phase separation in a symmetrical binary (A+B)
      Lennard-Jones fluid are studied via molecular dynamics simulations after
      quenching homogeneously mixed critical (50:50) systems to temperatures below the
      critical one. The morphology of the domains, rich in A or B particles, is
      observed to be bicontinuous. The early-time growth of the average domain size is
      found to be consistent with the Lifshitz-Slyozov law for diffusive domain
      coarsening. After a characteristic time, dependent on the temperature, we find a
      clear crossover to an extended viscous hydrodynamic regime where the domains grow
      linearly with time. Pattern formation in the present system is compared with that
      in solid binary mixtures, as a function of temperature. Important results for the
      finite-size and temperature effects on the small-wave-vector behavior of the
      scattering function are also presented.

PMID- 22587072
TI  - Universal statistics of vortex lines.
AB  - We study the vortex lines that are a feature of many random or disordered three
      dimensional systems. These show universal statistical properties on long length
      scales, and geometrical phase transitions analogous to percolation transitions
      but in distinct universality classes. The field theories for these problems have
      not previously been identified, so that while many numerical studies have been
      performed, a framework for interpreting the results has been lacking. We provide
      such a framework with mappings to simple supersymmetric models. Our main focus is
      on vortices in short-range-correlated complex fields, which show a geometrical
      phase transition that we argue is described by the CP(k|k) model (essentially the
      CP(n-1) model in the replica limit n->1). This can be seen by mapping a lattice
      version of the problem to a lattice gauge theory. A related field theory with a
      noncompact gauge field, the 'NCCP(k|k) model', is a supersymmetric extension of
      the standard dual theory for the XY transition, and we show that XY duality gives
      another way to understand the appearance of field theories of this type. The
      supersymmetric descriptions yield results relevant, for example, to vortices in
      the XY model and in superfluids, to optical vortices, and to certain models of
      cosmic strings. A distinct but related field theory, the RP(2l|2l) model (or the
      RP(n-1) model in the limit n->1) describes the unoriented vortices that occur,
      for instance, in nematic liquid crystals. Finally, we show that in two
      dimensions, a lattice gauge theory analogous to that discussed in three
      dimensions gives a simple way to see the known relation between two-dimensional
      percolation and the CP(k|k) sigma model with a theta term.

PMID- 22587073
TI  - Markov-switching multifractal models as another class of random-energy-like
      models in one-dimensional space.
AB  - We map the Markov-switching multifractal model (MSM) onto the random energy model
      (REM). The MSM is, like the REM, an exactly solvable model in one-dimensional
      space with nontrivial correlation functions. According to our results, four
      different statistical physics phases are possible in random walks with
      multifractal behavior. We also introduce the continuous branching version of the
      model, calculate the moments, and prove multiscaling behavior. Different phases
      have different multiscaling properties.

PMID- 22587074
TI  - Effects of inert species in the gas phase in a model for the catalytic oxidation
      of CO.
AB  - We study by kinetic Monte Carlo simulations the catalytic oxidation of carbon
      monoxide on a surface in the presence of contaminants in the gas phase. The
      process is simulated by a Ziff-Gulari-Barshad (ZGB) model that has been modified
      to include the effect of the contaminants and to eliminate an unphysical oxygen
      poisoned phase at very low CO partial pressures. The impurities can adsorb and
      desorb on the surface but otherwise remain inert. We find that if the impurities
      cannot desorb, no matter how small their proportion in the gas mixture, the
      reactive window and discontinuous transition to a CO poisoned phase at high CO
      pressures that characterize the original ZGB model disappear. The coverages
      become continuous, and once the surface has reached a steady state there is no
      production of CO(2). This is quite different from the behavior of systems in
      which the surface presents a fixed percentage of impurities. When the
      contaminants are allowed to desorb, the reactive phase appears again for CO
      pressures below a value that depends on the proportion of contaminants in the gas
      and on their desorption rate.

PMID- 22587075
TI  - Periodically driven underdamped periodic and washboard potential systems:
      dynamical states and stochastic resonance.
AB  - We have studied the motion of an underdamped Brownian particle in (i) a bistable
      periodic potential and (ii) washboard potentials subjected to a sinusoidal
      external field. The particles are shown to be effectively in two dynamical states
      of their trajectories with distinct amplitudes and phase relationship with the
      external drive. These dynamical states are stable with fixed energies at low
      temperatures, but transitions between them take place as the temperature is
      increased. The average input energy loss to the environment per period of the
      drive shows a stochastic resonance (SR) peak as a function of temperature for the
      underdamped system potentials studied. The occurrence of SR in these systems is
      explained using the statistics of transitions between the two dynamical states.

PMID- 22587076
TI  - Efficiency at maximum power output of quantum heat engines under finite-time
      operation.
AB  - We study the efficiency at maximum power, eta(m), of irreversible quantum Carnot
      engines (QCEs) that perform finite-time cycles between a hot and a cold reservoir
      at temperatures T(h) and T(c), respectively. For QCEs in the reversible limit
      (long cycle period, zero dissipation), eta(m) becomes identical to the Carnot
      efficiency eta(C)=1-T(c)/T(h). For QCE cycles in which nonadiabatic dissipation
      and the time spent on two adiabats are included, the efficiency eta(m) at maximum
      power output is bounded from above by eta(C)/(2-eta(C)) and from below by
      eta(C)/2. In the case of symmetric dissipation, the Curzon-Ahlborn efficiency
      eta(CA)=1-?(T(c)/T(h)) is recovered under the condition that the time allocation
      between the adiabats and the contact time with the reservoir satisfy a certain
      relation.

PMID- 22587077
TI  - Universality of the Ising and the S=1 model on Archimedean lattices: a Monte
      Carlo determination.
AB  - The Ising models S=1/2 and S=1 are studied by efficient Monte Carlo schemes on
      the (3,4,6,4) and the (3,3,3,3,6) Archimedean lattices. The algorithms used, a
      hybrid Metropolis-Wolff algorithm and a parallel tempering protocol, are briefly
      described and compared with the simple Metropolis algorithm. Accurate Monte Carlo
      data are produced at the exact critical temperatures of the Ising model for these
      lattices. Their finite-size analysis provide, with high accuracy, all critical
      exponents which, as expected, are the same with the well-known 2D Ising model
      exact values. A detailed finite-size scaling analysis of our Monte Carlo data for
      the S=1 model on the same lattices provides very clear evidence that this model
      obeys, also very well, the 2D Ising model critical exponents. As a result, we
      find that recent Monte Carlo simulations and attempts to define effective
      dimensionality for the S=1 model on these lattices are misleading. Accurate
      estimates are obtained for the critical amplitudes of the logarithmic expansions
      of the specific heat for both models on the two Archimedean lattices.

PMID- 22587078
TI  - Transition from single-file to two-dimensional diffusion of interacting particles
      in a quasi-one-dimensional channel.
AB  - Diffusive properties of a monodisperse system of interacting particles confined
      to a quasi-one-dimensional channel are studied using molecular dynamics
      simulations. We calculate numerically the mean-squared displacement (MSD) and
      investigate the influence of the width of the channel (or the strength of the
      confinement potential) on diffusion in finite-size channels of different shapes
      (i.e., straight and circular). The transition from single-file diffusion to the
      two-dimensional diffusion regime is investigated. This transition [regarding the
      calculation of the scaling exponent (alpha) of the MSD (Deltax(2)(t) ? t(alpha)]
      as a function of the width of the channel is shown to change depending on the
      channel's confinement profile. In particular, the transition can be either smooth
      (i.e., for a parabolic confinement potential) or rather sharp (i.e., for a hard
      wall potential), as distinct from infinite channels where this transition is
      abrupt. This result can be explained by qualitatively different distributions of
      the particle density for the different confinement potentials.

PMID- 22587079
TI  - Levy walks with velocity fluctuations.
AB  - The standard Levy walk is performed by a particle that moves ballistically
      between randomly occurring collisions when the intercollision time is a random
      variable governed by a power-law distribution. During instantaneous collision
      events, the particle randomly changes the direction of motion but maintains the
      same constant speed. We generalize the standard model to incorporate velocity
      fluctuations into the process. Two types of models are considered, namely (i)
      with a walker changing the direction and absolute value of its velocity during
      collisions only, and (ii) with a walker whose velocity continuously fluctuates.
      We present a full analytic evaluation of both models and emphasize the importance
      of initial conditions. We show that, in the limit of weak velocity fluctuations,
      the integral diffusion characteristics and the bulk of diffusion profiles are
      identical to those for the standard Levy walk. However, the type of underlying
      velocity fluctuations can be identified by looking at the ballistic regions of
      the diffusion profiles. Our analytical results are corroborated by numerical
      simulations.

PMID- 22587080
TI  - Non-Maxwellian behavior and quasistationary regimes near the modal solutions of
      the Fermi-Pasta-Ulam beta system.
AB  - In a recent paper [M. Leo, R. A. Leo, and P. Tempesta, J. Stat. Mech. (2011)
      P03003], it has been shown that the pi/2-mode exact nonlinear solution of the
      Fermi-Pasta-Ulam beta system, with periodic boundary conditions, admits two
      energy density thresholds. For values of the energy density epsilon below or
      above these thresholds, the solution is stable. Between them, the behavior of the
      solution is unstable, first recurrent and then chaotic. In this paper, we study
      the chaotic behavior between the two thresholds from a statistical point of view,
      by analyzing the distribution function of a dynamical variable that is zero when
      the solution is stable and fluctuates around zero when it is unstable. For
      mesoscopic systems clear numerical evidence emerges that near the second
      threshold, in a large range of the energy density, the numerical distribution is
      fitted accurately with a q-Gaussian distribution for very large integration
      times, suggesting the existence of a quasistationary state possessing a weakly
      chaotic behavior. A normal distribution is recovered in the thermodynamic limit.

PMID- 22587081
TI  - Stochastic theory of quantum vortex on a sphere.
AB  - A stochastic theory is presented for a quantum vortex in superfluid films coated
      on a two-dimensional sphere S^{2}. The starting point is the canonical equation
      of motion (Kirchhoff equation) for a point vortex, which is derived using the
      time-dependent Landau-Ginzburg theory. The vortex equation, which is equivalent
      to the spin equation, turns out to be the Langevin equation in presence of random
      forces. This is converted to the Fokker-Planck (FP) equation for the distribution
      function of a point vortex by using a functional integral technique. The FP
      equation is analyzed with special emphasis on the role of the pinning potential.
      By considering a typical form of the pinning potential, we address two problems:
      (i) The one is concerning an interplay between strength of the pinning potential
      and effective temperature, which discriminates the weak and strong coupling
      scheme to determine the solutions of the FP equation. (ii) The other is
      concerning a small diffusion limit, for which an asymptotic analysis is given
      using the functional integral to lead a compact expression of the distribution
      function. An extension to the vortex in nonspherical geometry is briefly
      discussed for the case of vortex on a plane and a pseudosphere.

PMID- 22587082
TI  - Shannon-entropy-based nonequilibrium "entropic" temperature of a general
      distribution.
AB  - The concept of temperature is one of the key ideas in describing the
      thermodynamical properties of systems. In classical statistical mechanics of
      ideal gases, the notion of temperature can be described in at least two different
      ways: the kinetic temperature (related to the average kinetic energy of the
      particles) and the thermodynamic temperature (related to the ratio between
      infinitesimal changes in entropy and energy). For the Boltzmann distribution, the
      two notions lead to the same result. However, for nonequilibrium phenomena, while
      the kinetic temperature has been commonly used both for theoretical and
      simulation purposes, there appears to be no corresponding general definition of
      thermodynamic or entropic temperature. In this paper, we consider the statistical
      or Shannon entropy of a system and use the "de Bruijn identity" from information
      theory (see Appendix A 2 for a derivation of this identity) to show that it is
      possible to define a "Shannon temperature" or "entropic temperature" T for a
      nonequilibrium system as the ratio between the average curvature of the
      Hamiltonian function associated with the system and the trace of the Fisher
      information matrix of the nonequilibrium probability distribution (see Appendix A
      1 for a definition of the Fisher information). We show that this definition
      subsumes many other attempts at defining entropic temperatures for nonequilibrium
      systems and is not restricted to equilibrium or near equilibrium systems.
      Intuitively, the gist of our approach is to use the Shannon or Gibbs entropy of a
      system and make use of the relation dS=dQ(rev)/T as a definition of temperature.
      We achieve this by positing a statistical notion of infinitesimal heating as the
      addition of uncorrelated random variables (in a special way). As an example of
      the utility of such a definition, we obtain the nonequilibrium entropic
      temperature for a system satisfying the Langevin equations. For such a system, we
      show that while the kinetic temperature is related to the changes in the energy
      of the system, the entropic or Shannon temperature is related to the changes in
      the entropy of the system. We show that this notion, together with the well known
      Cramer-Rao inequality in statistics demonstrates the validity of the second law
      of thermodynamics for such a nonequilibrium system.

PMID- 22587083
TI  - Riemannian geometry study of vapor-liquid phase equilibria and supercritical
      behavior of the Lennard-Jones fluid.
AB  - The behavior of thermodynamic response functions and the thermodynamic scalar
      curvature in the supercritical region have been studied for a Lennard-Jones fluid
      based on a revised modified Benedict-Webb-Rubin equation of state. Response
      function extrema are sometimes used to estimate the Widom line, which is
      characterized by the maxima of the correlation lengths. We calculated the Widom
      line for the Lennard-Jones fluid without using any response function extrema.
      Since the volume of the correlation length is proportional to the Riemannian
      thermodynamic scalar curvature, the locus of the Widom line follows the slope of
      maximum curvature. We show that the slope of the Widom line follows the slope of
      the isobaric heat capacity maximum only in the close vicinity of the critical
      point and that, therefore, the use of response function extrema in this context
      is problematic. Furthermore, we constructed the vapor-liquid coexistence line for
      the Lennard-Jones fluid using the fact that the correlation length, and therefore
      the thermodynamic scalar curvature, must be equal in the two coexisting phases.
      We compared the resulting phase envelope with those from simulation data where
      multiple histogram reweighting was used and found striking agreement between the
      two methods.

PMID- 22587084
TI  - Self-diffusivity and interdiffusivity of molten aluminum-copper alloys under
      pressure, derived from molecular dynamics.
AB  - We use molecular dynamics (MD) to simulate diffusion in molten aluminum-copper
      (AlCu) alloys. The self-diffusivities and Maxwell-Stefan diffusivities are
      calculated for AlCu mixtures using the Green-Kubo formulas at temperatures from
      1000 to 4000 K and pressures from 0 to 25 GPa, along with additional points at
      higher temperatures and pressures. The diffusivities are corrected for finite
      size effects. The Maxwell-Stefan diffusivity is compared to the diffusivity
      calculated from the self-diffusivities using a generalization of the Darken
      equation. We find that the effects of cross-correlation are small. Using the
      calculated self-diffusivities, we have assessed whether dilute hard-sphere and
      dilute Lennard-Jones models apply to the molten mixture. Neither of the two
      dilute gas diffusivities describes the diffusivity in molten Al and Cu. We report
      generalized analytic models for the self-diffusivities and interdiffusivity
      (mutual diffusivity) that fit the MD results well. The MD-derived transport
      coefficients are in good agreement with the available experimental data. We also
      report MD calculations of the viscosity and an analytic fit to those results. The
      ionic thermal conductivity is discussed briefly.

PMID- 22587085
TI  - Two liquid states of matter: a dynamic line on a phase diagram.
AB  - It is generally agreed that the supercritical region of a liquid consists of one
      single state (supercritical fluid). On the other hand, we show here that liquids
      in this region exist in two qualitatively different states: "rigid" and
      "nonrigid" liquids. Rigid to nonrigid transition corresponds to the condition
      tau~tau(0), where tau is the liquid relaxation time and tau(0) is the minimal
      period of transverse quasiharmonic waves. This condition defines a new dynamic
      crossover line on the phase diagram and corresponds to the loss of shear
      stiffness of a liquid at all available frequencies and, consequently, to the
      qualitative change in many important liquid properties. We analyze this line
      theoretically as well as in real and model fluids and show that the transition
      corresponds to the disappearance of high-frequency sound, to the disappearance of
      roton minima, qualitative changes in the temperature dependencies of sound
      velocity, diffusion, viscous flow, and thermal conductivity, an increase in
      particle thermal speed to half the speed of sound, and a reduction in the
      constant volume specific heat to 2k(B) per particle. In contrast to the Widom
      line that exists near the critical point only, the new dynamic line is universal:
      It separates two liquid states at arbitrarily high pressure and temperature and
      exists in systems where liquid-gas transition and the critical point are absent
      altogether. We propose to call the new dynamic line on the phase diagram "Frenkel
      line".

PMID- 22587086
TI  - Polymerlike statistical characterization of two-dimensional granular chains.
AB  - Statistical behaviors of packing collections of granular chains in a two
      dimensional container have been investigated experimentally. On compaction from
      their own gravity, the longer chains pack into a structure with lower packing
      density due to the prevalence of backbone loops. The packing of chains can be
      considered as the jamming of the granular system. The structure factor of packing
      chains shows scaling behavior g(q)~q(-2) in good agreement with dense polymer
      solutions. In addition, we compute various probability distributions of distances
      and estimate three crucial contact exponents, finding that the scaling behavior
      from granular chains is in accord with the theoretical expectation of polymers.
      Finally, an orientational anticorrelation of granular chains is observed by bond
      bond correlation function, which agrees with the results in the two-dimensional
      model of compact polymers.

PMID- 22587087
TI  - Phase transition in peristaltic transport of frictionless granular particles.
AB  - Flows of dissipative particles driven by the peristaltic motion of a tube are
      numerically studied. A transition from a slow "unjammed" flow to a fast "jammed"
      flow is found through the observation of the flow rate at a critical width of the
      bottleneck of a peristaltic tube. It is also found that the average and
      fluctuation of the transition time, and the peak value of the second moment of
      the flow rate exhibit power-law divergence near the critical point and that these
      variables satisfy scaling relationships near the critical point. The dependence
      of the critical width and exponents on the peristaltic speed and the density is
      also discussed.

PMID- 22587088
TI  - Force chains and contact network topology in sheared packings of elongated
      particles.
AB  - By means of contact dynamic simulations, we investigate the contact network
      topology and force chains in two-dimensional packings of elongated particles
      subjected to biaxial shearing. The morphology of large packings of elongated
      particles in quasistatic equilibrium is complex due to the combined effects of
      local nematic ordering of the particles and orientations of contacts between
      particles. The effect of elongation on shear behavior and dilatancy was
      investigated in detail in a previous paper [Azema and Radjai, Phys. Rev. E 81,
      051304 (2010)]. Here, we show how particle elongation affects force distributions
      and force-fabric anisotropy via various local structures allowed by steric
      exclusions and the requirement of force balance. We find that the force
      distributions become increasingly broader as particles become more elongated.
      Interestingly, the weak force network transforms from a passive stabilizing agent
      with respect to strong force chains to an active force-transmitting network for
      the whole system. The strongest force chains are carried by side-side contacts
      oriented along the principal stress direction.

PMID- 22587089
TI  - Contact anisotropy and coordination number for a granular assembly: a comparison
      of distinct-element-method simulations and theory.
AB  - We study an ideal granular aggregate consisting of elastic spherical particles,
      isotropic in stress and anisotropic in the contact network. Because of the
      contact anisotropy, a confining pressure applied at zero deviatoric stress,
      produces shear strain as well as volume strain. Our goal is to predict the
      coordination number k, the average number of contacts per particle, and the
      magnitude of the contact anisotropy E, from knowledge of the elastic moduli of
      the aggregate. We do this through a theoretical model based upon the well known
      effective medium theory. However, rather than focusing on the moduli, we consider
      their ratios over the moduli of an equivalent isotropic state. We observe good
      agreement between numerical simulation and theory.

PMID- 22587090
TI  - Ringlike spin segregation of binary mixtures in a high-velocity rotating drum.
AB  - This study presents molecular dynamics simulations on the segregation of binary
      mixtures in a high-velocity rotating drum. Depending on the ratio between the
      particle radius and density, similarities to the Brazil-nut effect and its
      reverse form are shown in the ringlike spin segregation patterns in radial
      direction. The smaller and heavier particles accumulated toward the drum wall,
      whereas the bigger and lighter particles accumulated toward the drum center. The
      effects of particle radius and density on the segregation states were quantified
      and the phase diagram of segregation in the rho(b)/rho(s) - r(b)/r(s) space was
      plotted. The observed phenomena can be explained by the combined percolation and
      the buoyancy effects.

PMID- 22587091
TI  - Elastic waves in the presence of a granular shear band formed by direct shear.
AB  - The propagation of elastic waves in a box under direct shear, filled with glass
      beads and being sheared at constant rates, is studied experimentally and
      theoretically. The respective velocities are shown to be essentially unchanged
      from that in a static granular system under the same pressure and shear stress
      but without a shear band. Influence of shear band on sound behaviors are also
      briefly discussed.

PMID- 22587092
TI  - Recurrent inflation and collapse in horizontally shaken granular materials.
AB  - We report a striking effect observed experimentally in several granular materials
      when shaken horizontally: The material displays a recurrent alternation between a
      slow inflation phase, characterized by an increase in its volume, and a fast
      collapse phase, when the volume abruptly returns to its original value. The
      frequency of such phase alternations is totally decoupled from the frequency of
      the external drive. We argue that the inflation and collapse alternation arises
      from an interplay between the mechanical stability of the material and Reynolds
      dilatancy due to convective motion.

PMID- 22587093
TI  - Wave propagation in random granular chains.
AB  - The influence of randomness on wave propagation in one-dimensional chains of
      spherical granular media is investigated. The interaction between the elastic
      spheres is modeled using the classical Hertzian contact law. Randomness is
      introduced in the discrete model using random distributions of particle mass,
      Young's modulus, or radius. Of particular interest in this study is the
      quantification of the attenuation in the amplitude of the impulse associated with
      various levels of randomness: two distinct regimes of decay are observed,
      characterized by an exponential or a power law, respectively. The responses are
      normalized to represent a vast array of material parameters and impact
      conditions. The virial theorem is applied to investigate the transfer from
      potential to kinetic energy components in the system for different levels of
      randomness. The level of attenuation in the two decay regimes is compared for the
      three different sources of randomness and it is found that randomness in radius
      leads to the maximum rate of decay in the exponential regime of wave propagation.

PMID- 22587094
TI  - How relative humidity affects random packing experiments.
AB  - The influence of relative humidity (RH) on the extremely slow compaction dynamics
      of a granular assembly has been experimentally investigated. Millimeter-sized
      glass beads are considered. Compaction curves are fitted by stretched
      exponentials with characteristic time tau and exponent delta, which are seen to
      be deeply affected by the moisture content. A kinetic model, taking into account
      both triboelectric and capillary effects, is in excellent agreement with our
      results. It confirms the existence of an optimal condition at a relative humidity
      ~45% for minimizing cohesive interactions between glass beads. The exponent delta
      is seen to depend strongly on the diffusive character of grains and voids inside
      the packing: diffusion for cohesiveless particles and subdiffusion when cohesion
      plays a role. As a consequence, the RH represents a relevant parameter that
      should be reported for every experimental work on a slowly driven dense random
      packing.

PMID- 22587095
TI  - Easy-use and low-cost fiber-based two-color dynamic light-scattering apparatus.
AB  - We present a small and compact two-color cross-correlation light-scattering setup
      designed to study the structure and dynamics of colloidal suspensions in the
      regime of considerable turbidity. Using a homemade concentric four-arm
      goniometer, combined with fiber-optical illumination and detection devices,
      allows an easy and long time stable alignment-even under a temperature variation
      of ~5  degrees C. Tests with a nearly multiple scattering free suspension of
      small Rayleigh scatterers show intercepts in cross correlation near 0.4 over a
      wide range of scattering angles from 20 degrees  to 150 degrees . Measuring
      slightly turbid samples in cross-correlation mode multiple scattering is
      sufficiently suppressed allowing the determination of multiple scattering free
      dynamic structure factors as well as particle form factors.

PMID- 22587096
TI  - Nonaffine measures of particle displacements in sheared colloidal glasses.
AB  - The nonaffine motion of particles is central to the relaxation and flow of
      glasses. It is usually assumed in plasticity theories that nonaffine
      rearrangements are localized and uncorrelated. Here we present evidence that this
      assumption may not hold. We investigate and compare systematically different
      measures of nonaffinity in a sheared colloidal glass by tracking the motion of
      the individual particles directly with confocal microscopy. We show that besides
      differences in the appearance and degree of localization of nonaffine
      displacements, the nature of their fluctuations is very similar. At intermediate
      times, all spatial correlation functions display robust power-law behavior,
      clearly demonstrating long-range correlations and critical behavior of the driven
      glass, in contrast to the assumptions of plasticity theories. We show that on
      long-time scales, correlations become finite and plasticity theories may apply.

PMID- 22587097
TI  - Dynamics of confined water reconstructed from inelastic x-ray scattering
      measurements of bulk response functions.
AB  - Nanoconfined water and surface-structured water impacts a broad range of fields.
      For water confined between hydrophilic surfaces, measurements and simulations
      have shown conflicting results ranging from "liquidlike" to "solidlike" behavior,
      from bulklike water viscosity to viscosity orders of magnitude higher. Here, we
      investigate how a homogeneous fluid behaves under nanoconfinement using its bulk
      response function: The Green's function of water extracted from a library of
      S(q,omega) inelastic x-ray scattering data is used to make femtosecond movies of
      nanoconfined water. Between two confining surfaces, the structure undergoes
      drastic changes as a function of surface separation. For surface separations of
      ~9 A, although the surface-associated hydration layers are highly deformed, they
      are separated by a layer of bulklike water. For separations of ~6 A, the two
      surface-associated hydration layers are forced to reconstruct into a single layer
      that modulates between localized "frozen' and delocalized "melted" structures due
      to interference of density fields. These results potentially reconcile recent
      conflicting experiments. Importantly, we find a different delocalized wetting
      regime for nanoconfined water between surfaces with high spatial frequency charge
      densities, where water is organized into delocalized hydration layers instead of
      localized hydration shells, and are strongly resistant to 'freezing' down to
      molecular distances (<6 A).

PMID- 22587098
TI  - Stagnation point flow of wormlike micellar solutions in a microfluidic cross-slot
      device: effects of surfactant concentration and ionic environment.
AB  - We employ the techniques of microparticle image velocimetry and full-field
      birefringence microscopy combined with mechanical measurements of the pressure
      drop to perform a detailed characterization of the extensional rheology and
      elastic flow instabilities observed for a range of wormlike micellar solutions
      flowing through a microfluidic cross-slot device. As the flow rate through the
      device is increased, the flow first bifurcates from a steady symmetric to a
      steady asymmetric configuration characterized by a birefringent strand of highly
      aligned micellar chains oriented along the shear-free centerline of the flow
      field. At higher flow rates the flow becomes three dimensional and time dependent
      and is characterized by aperiodic spatiotemporal fluctuations of the birefringent
      strand. The extensional properties and critical conditions for the onset of flow
      instabilities in the fluids are highly dependent on the fluid formulation
      (surfactant concentration and ionic strength) and the resulting changes in the
      linear viscoelasticity and nonlinear shear rheology of the fluids. By combining
      the measurements of critical conditions for the flow transitions with the
      viscometric material properties and the degree of shear-thinning characterizing
      each test fluid, it is possible to construct a stability diagram for viscoelastic
      flow of complex fluids in the cross-slot geometry.

PMID- 22587099
TI  - Temperature dependence of the structure of protein hydration water and the liquid
      liquid transition.
AB  - We study the temperature dependence of the structure and orientation of the first
      hydration layers of the protein lysozyme and compare it with the situation for a
      model homogeneous hydrophobic surface, a graphene sheet. We show that in both
      cases these layers are significantly better structured than bulk water. The
      geometrical constraint of the interface makes the water molecules adjacent to the
      surface lose one water-water hydrogen bond and expel the fourth neighbors away
      from the surface, lowering local density. We show that a decrease in temperature
      improves the ordering of the hydration water molecules, preserving such a
      geometrical effect. For the case of graphene, this favors an ice Ih-like local
      structuring, similar to the water-air interface but in the opposite way along the
      c axis of the basal plane (while the vicinal water molecules of the air interface
      orient a hydrogen atom toward the surface, the oxygens of the water molecules
      close to the graphene plane orient a lone pair in such a direction). In turn, the
      case of the first hydration layers of the lysozyme molecule is shown to be more
      complicated, but still displaying signs of both kinds of behavior, together with
      a tendency of the proximal water molecules to hydrogen bond to the protein both
      as donors and as acceptors. Additionally, we make evident the existence of
      signatures of a liquid-liquid transition (Widom line crossing) in different
      structural parameters at the temperature corresponding to the dynamic transition
      incorrectly referred to as "the protein glass transition."

PMID- 22587100
TI  - Free-energy landscape for cage breaking of three hard disks.
AB  - We investigate cage breaking in dense hard-disk systems using a model of three
      Brownian disks confined within a circular corral. This system has a six
      dimensional configuration space, but can be equivalently thought to explore a
      symmetric one-dimensional free-energy landscape containing two energy minima
      separated by an energy barrier. The exact free-energy landscape can be calculated
      as a function of system size by a direct enumeration of states. Results of
      simulations show the average time between cage breaking events follows an
      Arrhenius scaling when the energy barrier is large. We also discuss some of the
      consequences of using a one-dimensional representation to understand dynamics
      through a multidimensional space, such as diffusion acquiring spatial dependence
      and discontinuities in spatial derivatives of free energy.

PMID- 22587101
TI  - Phase separation in fluids exposed to spatially periodic external fields.
AB  - When a fluid is confined within a spatially periodic external field, the liquid
      vapor transition is replaced by a different transition called laser-induced
      condensation (LIC) [Gotze et al., Mol. Phys. 101, 1651 (2003)]. In d=3
      dimensions, the periodic field induces an additional phase, characterized by
      large density modulations along the field direction. At the triple point, all
      three phases (modulated, vapor, and liquid) coexist. At temperatures slightly
      above the triple point and for low (high) values of the chemical potential, two
      phase coexistence between the modulated phase and the vapor (liquid) is observed;
      by increasing the temperature further, both coexistence regions terminate in
      critical points. In this paper, we reconsider LIC using the Ising model to
      resolve a number of open issues. To be specific, we (1) determine the
      universality class of the LIC critical points and elucidate the nature of the
      correlations along the field direction, (2) present a mean-field analysis to show
      how the LIC phase diagram changes as a function of the field wavelength and
      amplitude, (3) develop a simulation method by which the extremely low tension of
      the interface between modulated and vapor or liquid phase can be measured, (4)
      present a finite-size scaling analysis to accurately extract the LIC triple point
      from finite-size simulation data, and (5) consider the fate of LIC in d=2
      dimensions.

PMID- 22587102
TI  - Onsager approach to the one-dimensional solidification problem and its relation
      to the phase-field description.
AB  - We give a general phenomenological description of the steady-state 1D front
      propagation problem in two cases: the solidification of a pure material and the
      isothermal solidification of two-component dilute alloys. The solidification of a
      pure material is controlled by the heat transport in the bulk and the interface
      kinetics. The isothermal solidification of two-component alloys is controlled by
      the diffusion in the bulk and the interface kinetics. We find that the condition
      of positive-definiteness of the symmetric Onsager matrix of interface kinetic
      coefficients still allows an arbitrary sign of the slope of the velocity
      concentration line near the solidus in the alloy problem or of the velocity
      temperature line in the case of solidification of a pure material. This result
      offers a very simple and elegant way to describe the interesting phenomenon of a
      possible non-single-value behavior of velocity versus concentration that has
      previously been discussed by different approaches. We also discuss the relation
      of this Onsager approach to the thin-interface limit of the phase-field
      description.

PMID- 22587103
TI  - Lowering liquid-solid interfacial thermal resistance with nanopatterned surfaces.
AB  - Advances in nanopatterned surface fabrication have sparked an interest in
      studying surface topology effects on heat transfer across liquid-solid interfaces
      (LSIs). In this study, molecular dynamics (MD) simulations are conducted to
      examine the effects of surface nanopatterning on the thermal resistance across
      LSIs. It is shown that nanopatterning can strongly influence the wetting behavior
      and vibrational properties of a solid surface. The combination of these two
      factors has a direct effect on the degree of vibrational coupling between the
      adsorbed liquid and the solid surface. A strong correlation exists between this
      coupling and the resulting LSI thermal resistance.

PMID- 22587104
TI  - Defects in crystalline packings of twisted filament bundles. I. Continuum theory
      of disclinations.
AB  - We develop the theory of the coupling between in-plane order and out-of-plane
      geometry in twisted, two-dimensionally ordered filament bundles based on the
      nonlinear continuum elasticity theory of columnar materials. We show that twisted
      textures of filament backbones necessarily introduce stresses into the cross
      sectional packing of bundles and that these stresses are formally equivalent to
      the geometrically induced stresses generated in thin elastic sheets that are
      forced to adopt spherical curvature. As in the case of crystalline order on
      curved membranes, geometrically induced stresses couple elastically to the
      presence of topological defects in the in-plane order. We derive the effective
      theory of multiple disclination defects in the cross section of bundle with a
      fixed twist and show that above a critical degree of twist, one or more fivefold
      disclinations is favored in the elastic energy ground state. We study the
      structure and energetics of multidisclination packings based on models of
      equilibrium and nonequilibrium cross-sectional order.

PMID- 22587105
TI  - Defects in crystalline packings of twisted filament bundles. II. Dislocations and
      grain boundaries.
AB  - Twisted and ropelike assemblies of filamentous molecules are common and vital
      structural elements in cells and tissues of living organisms. We study the
      intrinsic frustration occurring in these materials between the two-dimensional
      organization of filaments in cross section and out-of-plane interfilament twist
      in bundles. Using nonlinear continuum elasticity theory of columnar materials, we
      study the favorable coupling of twist-induced stresses to the presence of edge
      dislocations in the lattice packing of bundles, which leads to a restructuring of
      the ground-state order of these materials at intermediate twist. The stability of
      dislocations increases as both the degree of twist and lateral bundle size grow.
      We show that in ground states of large bundles, multiple dislocations pile up
      into linear arrays, radial grain boundaries, whose number and length grows with
      bundle twist, giving rise to a rich class of "polycrystalline" packings.

PMID- 22587106
TI  - Excess equimolar radius of liquid drops.
AB  - The curvature dependence of the surface tension is related to the excess
      equimolar radius of liquid drops, i.e., the deviation of the equimolar radius
      from the radius defined by the macroscopic capillarity approximation. Based on
      the Tolman [J. Chem. Phys. 17, 333 (1949)] approach and its interpretation by
      Nijmeijer et al. [J. Chem. Phys. 96, 565 (1991)], the surface tension of
      spherical interfaces is analyzed in terms of the pressure difference due to
      curvature. In the present study, the excess equimolar radius, which can be
      obtained directly from the density profile, is used instead of the Tolman length.
      Liquid drops of the truncated and shifted Lennard-Jones fluid are investigated by
      molecular dynamics simulation in the canonical ensemble, with equimolar radii
      ranging from 4 to 33 times the Lennard-Jones size parameter sigma. In these
      simulations, the magnitude of the excess equimolar radius is shown to be smaller
      than sigma/2. This suggests that the surface tension of liquid drops at the
      nanometer length scale is much closer to that of the planar vapor-liquid
      interface than reported in studies based on the mechanical route.

PMID- 22587107
TI  - Scaling properties of fluid adsorption near the base of a cylinder.
AB  - We consider the adsorption of fluid at the foot of a cylinder that protrudes from
      a flat substrate made of the same material. Provided the contact angle theta is
      small enough, a drop of liquid condenses near the base, the size of which can be
      determined using simple macroscopic arguments. The adsorption in this geometry
      shows scaling behavior related to a number of different interfacial phase
      transitions and, for systems with short-ranged forces, shows a remarkable
      property; for small theta, the height of the drop (measured from the base) and
      the width (measured from the cylinder axis) are near identical to expressions for
      the thickness and parallel correlation length for microscopic wetting films (at
      planar walls). The only difference is that the bulk correlation length is
      replaced by the radius of the cylinder. By taking into account the correct
      singular behavior of the line tension we show that this geometrical amplification
      of the microscopic lengths occurs for second-order, first-order, and complete
      wetting transitions, and is specific to three dimensions. Similar phenomena
      occurs for long-ranged forces, and shows crossover scaling behavior.

PMID- 22587108
TI  - Topological and geometric decomposition of nematic textures.
AB  - Directional media, such as nematic liquid crystals and ferromagnets, are
      characterized by their topologically stabilized defects in directional order. In
      nematics, boundary conditions and surface-treated inclusions often create complex
      structures, which are difficult to classify. Topological charge of point defects
      in nematics has ambiguously defined sign, and its additivity cannot be ensured
      when defects are observed separately. We demonstrate how the topological charge
      of complex defect structures can be determined by identifying and counting parts
      of the texture that satisfy simple geometric rules. We introduce a parameter
      called the defect rank and show that it corresponds to what is intuitively
      perceived as a point charge based on the properties of the director field.
      Finally, we discuss the role of free-energy constraints in the validity of the
      classification with the defect rank.

PMID- 22587109
TI  - Modeling the reflection from cholesteric liquid crystals using modal analysis and
      mode matching.
AB  - The reflection and transmission spectra from right-handed cholesteric liquid
      crystals are computed in the visible region for a linearly, circularly, or
      elliptically polarized incident plane wave at oblique incidence. The liquid
      crystal cell is sandwiched between dielectric layers of certain thickness and
      refractive index. The underlined formulation is based on a modal analysis of the
      governing field expressions in the dielectric and liquid-crystal regions. A
      representative matrix system is obtained after enforcing the continuity of the
      tangential electric and magnetic fields at the material interfaces. Solution of
      the governing matrix system results in the reflectance and transmittance for a
      given wavelength. Numerical results for both normal and oblique incidence were
      obtained and compared with data published in the literature. The underlined
      formulation is effective, accurate, robust, versatile, and computationally
      efficient.

PMID- 22587110
TI  - Smectic-A-smectic-C phase transition in biaxial disordered environments.
AB  - We study the smectic-A-smectic-C phase transition in biaxial disordered
      environments, e.g., fully anisotropic aerogel. We find that both the A and C
      phases belong to the universality class of the "XY Bragg glass," and therefore
      have quasi-long-ranged translational smectic order. The phase transition itself
      belongs to a new universality class, which we study using an epsilon=7/2-d
      expansion. We find a stable fixed point, which implies a continuous transition,
      the critical exponents of which we calculate.

PMID- 22587111
TI  - Electro-optic response of the anticlinic, antiferroelectric liquid-crystal phase
      of a biaxial bent-core molecule with tilt angle near 45?.
AB  - We describe the unusual electro-optic response of a biaxial bent-core liquid
      crystal molecule that exhibits an anticlinic, antiferroelectric smectic phase (Sm
      C(A)P(A)) with a molecular tilt angle close to 45 degrees . In the ground state,
      the sample shows very low birefringence. A weak applied electric field distorts
      the antiferroelectric ground state, inducing a small azimuthal reorientation of
      the molecules on the tilt cone. This results in only a modest increase in the
      birefringence but an anomalously large (~40 degrees ) analog rotation of the
      extinction direction. This unusual electro-optic response is shown to be a
      consequence of the molecular biaxiality.

PMID- 22587112
TI  - Molecular-field-theory approach to the Landau theory of liquid crystals: uniaxial
      and biaxial nematics.
AB  - Nematic liquid crystal phase diagrams in temperature-biaxiality space are usually
      complex. We construct a Landau theory based on the analogous molecular-field
      theory for orthorhombic biaxial nematic fluids. A formal procedure yields
      coefficients (some of which, unusually, can be tensorial) in this Landau
      expansion, correctly predicts the complete set of invariants formed from the
      ordering tensors, and avoids ad hoc parametrization of the molecular biaxiality.
      By regularizing the Landau expansion to avoid unwanted order parameter
      divergences at low temperatures, we predict phase behavior over the whole range
      of biaxiality. The resulting phase diagrams have the same topology as those of
      molecular-field theory.

PMID- 22587113
TI  - Modeling mechanochromatic lamellar gels.
AB  - Consisting of alternating swelling and nonswelling polymeric layers (SLs and
      NLs), lamellar gels are one-dimensional photonic crystals with mechanically
      tunable optical properties. The lamellar structure induces a constraint between
      the SLs and the NLs, resulting in a highly anisotropic swelling behavior that is
      coupled with deformation. The coupling gives rise to the mechanochromatic effect,
      i.e., the color change in the material in response to mechanical deformations. A
      quantitative understanding of the coupling behavior is the key to many
      applications. This paper formulates a nonlinear continuum model for lamellar gels
      by considering the constrained swelling and anisotropic deformation in both
      layers. A finite-element method is further developed to simulate the
      mechanochromatic response of a lamellar gel undergoing a nonuniform field.

PMID- 22587114
TI  - Striped networks and other hierarchical structures in AmBmCn (2m+n)-miktoarm star
      terpolymer melts.
AB  - Using dissipative particle dynamics simulations we give numerical evidence of the
      formation of "striped" (or AB alternating) diamond and gyroid network structures
      and other hierarchical morphologies in A(m)B(m)C(n) (2m+n)-miktoarm star
      terpolymers where the main variable is the ratio x=n/m with m,n being the number
      of equal length polymer arms of A and B and C, respectively. The formed networks
      are purely a result of the star topology, as clearly shown by direct comparison
      with parallel ABC miktoarm star terpolymer simulations with matching overall
      composition. Progressively changing x, the system adopts the following phase
      sequence: three-colored lamellae, C spheres embedded in AB lamellae, C spheres
      decorating AB lamellae, three-colored [6.6.6] tiling, AB striped diamond network,
      AB striped gyroid network, AB striped hexagonally arranged cylinders, and finally
      AB striped globular aggregates. The striped gyroid is particularly interesting as
      it constitutes an inherently chiral structure made from achiral building blocks.

PMID- 22587115
TI  - Mechanical desorption of a single chain: unusual aspects of phase coexistence at
      a first-order transition.
AB  - The phase transition occurring when a single polymer chain adsorbed at a planar
      solid surface is mechanically desorbed is analyzed in two statistical ensembles.
      In the force ensemble, a constant force applied to the nongrafted end of the
      chain (that is grafted at its other end) is used as a given external control
      variable. In the z-ensemble, the displacement z of this nongrafted end from the
      surface is taken as the externally controlled variable. Basic thermodynamic
      parameters, such as the adsorption energy, exhibit a very different behavior as a
      function of these control parameters. In the thermodynamic limit of infinite
      chain length the desorption transition with the force as a control parameter
      clearly is discontinuous, while in the z-ensemble continuous variations are
      found. However, one should not be misled by a too-naive application of the
      Ehrenfest criterion to consider the transition as a continuous transition:
      rather, one traverses a two-phase coexistence region, where part of the chain is
      still adsorbed and the other part desorbed and stretched. Similarities with and
      differences from two-phase coexistence at vapor-liquid transitions are pointed
      out. The rounding of the singularities due to finite chain length is illustrated
      by exact calculations for the nonreversal random walk model on the simple cubic
      lattice. A new concept of local order parameter profiles for the description of
      the mechanical desorption of adsorbed polymers is suggested. This concept give
      evidence for both the existence of two-phase coexistence within single polymer
      chains for this transition and the anomalous character of this two-phase
      coexistence. Consequences for the proper interpretation of experiments performed
      in different ensembles are briefly mentioned.

PMID- 22587116
TI  - Phase diagrams of knotted and unknotted ring polymers.
AB  - The phase diagram for a lattice ring polymer under applied force, with variable
      solvent quality, for different topological knot states, is determined for the
      first time. In addition to eliminating pseudophases where the polymer is
      flattened into a single layer, it is found that nontrivial knots result in
      additional pseudophases under tensile force conditions.

PMID- 22587117
TI  - Bioinspired, mechanical, deterministic fractal model for hierarchical suture
      joints.
AB  - Many biological systems possess hierarchical and fractal-like interfaces and
      joint structures that bear and transmit loads, absorb energy, and accommodate
      growth, respiration, and/or locomotion. In this paper, an elastic deterministic
      fractal composite mechanical model was formulated to quantitatively investigate
      the role of structural hierarchy on the stiffness, strength, and failure of
      suture joints. From this model, it was revealed that the number of hierarchies
      (N) can be used to tailor and to amplify mechanical properties nonlinearly and
      with high sensitivity over a wide range of values (orders of magnitude) for a
      given volume and weight. Additionally, increasing hierarchy was found to result
      in mechanical interlocking of higher-order teeth, which creates additional load
      resistance capability, thereby preventing catastrophic failure in major teeth and
      providing flaw tolerance. Hence, this paper shows that the diversity of
      hierarchical and fractal-like interfaces and joints found in nature have
      definitive functional consequences and is an effective geometric-structural
      strategy to achieve different properties with limited material options in nature
      when other structural geometries and parameters are biologically challenging or
      inaccessible. This paper also indicates the use of hierarchy as a design strategy
      to increase design space and provides predictive capabilities to guide the
      mechanical design of synthetic flaw-tolerant bioinspired interfaces and joints.

PMID- 22587118
TI  - Membrane heterogeneity: manifestation of a curvature-induced microemulsion.
AB  - To explain the appearance of heterogeneities in the plasma membrane, I propose a
      hypothesis which begins with the observation that fluctuations in the membrane
      curvature are coupled to the difference between compositions of one leaf and the
      other. Because of this coupling, the most easily excited fluctuations can occur
      at nonzero wave numbers. When the coupling is sufficiently strong, it is well
      known that it leads to microphase separation and modulated phases. I note that
      when the coupling is less strong, the tendency toward modulation remains manifest
      in a liquid phase that exhibits a transient structure of a characteristic size,
      that is, it is a microemulsion. The characteristic size of the fluctuating
      domains is estimated to be on the order of 100 nm, and experiments to verify this
      hypothesis are proposed.

PMID- 22587119
TI  - Solvable model for polymorphic dynamics of biofilaments.
AB  - We investigate an analytically tractable toy model for thermally induced
      polymorphic dynamics of cooperatively rearranging biofilaments-like microtubules.
      The proposed four-block model, which can be seen as a coarse-grained
      approximation of the full polymorphic tube model, permits a complete analytical
      treatment of all thermodynamic properties including correlation functions and
      angular Fourier mode distributions. Due to its mathematical tractability the
      model straightforwardly leads to some physical insights in recently discussed
      phenomena like the "length dependent persistence length." We show that a
      polymorphic filament can disguise itself as a classical worm-like chain on small
      and on large scales and yet display distinct anomalous tell-tale features
      indicating an inner switching dynamics on intermediate length scales.

PMID- 22587120
TI  - Analytical calculation of protein production distributions in models of clustered
      protein expression.
AB  - A theoretical framework is presented, which derives chemical master equations for
      the number of protein molecules produced in a given time window, It is applied to
      derive analytical solutions that describe protein production distributions for
      the random bursting model (with an exponential or geometric burst-size
      distribution) and the clustering model. This distribution is experimentally
      observable using recently developed, single-molecule gene expression experiments.
      Furthermore, intrinsic stochasticity in a gene's expression can be calculated
      from protein production distributions using a new, time-dependent noise curve
      analysis. Different models of gene expression are compared with respect to their
      protein production distributions and intrinsic stochasticity, revealing the
      effects of molecular memory and burstlike expression on fluctuations in gene
      expression. It is distinct from and provides major advantages over measurements
      of steady-state concentrations.

PMID- 22587121
TI  - Rupture of a biomembrane under dynamic surface tension.
AB  - How long will a fluid membrane vesicle stressed with a steady ramp of
      micropipette last before rupture? Or conversely, how high should the surface
      tension be to rupture such a membrane? To answer these challenging questions we
      developed a theoretical framework that allows for the description and
      reproduction of dynamic tension spectroscopy (DTS) observations. The kinetics of
      the membrane rupture under ramps of surface tension is described as a succession
      of an initial pore formation followed by the Brownian process of the pore radius
      crossing the time-dependent energy barrier. We present the formalism and a derive
      (formal) analytical expression of the survival probability describing the fate of
      the membrane under DTS conditions. Using numerical simulations for the membrane
      prepared in an initial state with a given distribution of times for pore
      nucleation, we study the membrane lifetime (or inverse of rupture rate) and
      distribution of membrane surface tension at rupture as a function of membrane
      characteristics like pore nucleation rate, the energy barrier to failure, and
      tension loading rate. It is found that simulations reproduce the main features of
      DTS experiments, particularly the pore nucleation and pore-size diffusion
      controlled limits of membrane rupture dynamics. This approach can be adapted and
      applied to processes of permeation and pore opening in membranes
      (electroporation, membrane disruption by antimicrobial peptides, vesicle fusion).

PMID- 22587122
TI  - Soliton concepts and protein structure.
AB  - Structural classification shows that the number of different protein folds is
      surprisingly small. It also appears that proteins are built in a modular fashion
      from a relatively small number of components. Here we propose that the modular
      building blocks are made of the dark soliton solution of a generalized discrete
      nonlinear Schrodinger equation. We find that practically all protein loops can be
      obtained simply by scaling the size and by joining together a number of copies of
      the soliton, one after another. The soliton has only two loop-specific
      parameters, and we compute their statistical distribution in the Protein Data
      Bank (PDB). We explicitly construct a collection of 200 sets of parameters, each
      determining a soliton profile that describes a different short loop. The ensuing
      profiles cover practically all those proteins in PDB that have a resolution which
      is better than 2.0 A, with a precision such that the average root-mean-square
      distance between the loop and its soliton is less than the experimental B-factor
      fluctuation distance. We also present two examples that describe how the loop
      library can be employed both to model and to analyze folded proteins.

PMID- 22587123
TI  - Kinetic Monte Carlo and cellular particle dynamics simulations of multicellular
      systems.
AB  - Computer modeling of multicellular systems has been a valuable tool for
      interpreting and guiding in vitro experiments relevant to embryonic
      morphogenesis, tumor growth, angiogenesis and, lately, structure formation
      following the printing of cell aggregates as bioink particles. Here we formulate
      two computer simulation methods: (1) a kinetic Monte Carlo (KMC) and (2) a
      cellular particle dynamics (CPD) method, which are capable of describing and
      predicting the shape evolution in time of three-dimensional multicellular systems
      during their biomechanical relaxation. Our work is motivated by the need of
      developing quantitative methods for optimizing postprinting structure formation
      in bioprinting-assisted tissue engineering. The KMC and CPD model parameters are
      determined and calibrated by using an original computational-theoretical
      experimental framework applied to the fusion of two spherical cell aggregates.
      The two methods are used to predict the (1) formation of a toroidal structure
      through fusion of spherical aggregates and (2) cell sorting within an aggregate
      formed by two types of cells with different adhesivities.

PMID- 22587124
TI  - Multicomponent hydrodynamic model for heterogeneous biofilms: two-dimensional
      numerical simulations of growth and interaction with flows.
AB  - We develop a tricomponent (ternary) hydrodynamic model for multiphase flows of
      biomass and solvent mixtures, which we employ to simulate biofilm. In this model,
      the three predominant effective components in biofilms, which are the
      extracellular polymeric substance (EPS) network, the bacteria, and the effective
      solvent (consisting of the solvent and nutrient, etc.), are modeled explicitly.
      The tricomponent fluid mixture is assumed incompressible as a whole, while
      intercomponent mixing, dissipation, and conversion are allowed among the
      effective components. Bacterial growth and EPS production due to the growing
      bacterial population are modeled in the biomass transport equations. Bacterial
      decay due to starvation and natural causes is accounted for in the bacterial
      population dynamics to capture the possible bacterial population reduction due to
      the depletion of the nutrient. In the growth regime for biofilms, the mixture
      behaves like a multiphase viscous fluid, in which the molecular relaxation is
      negligible in the corresponding time scale. In this regime, the dynamics of
      biofilm growth in the solvent (water) are simulated using a two-dimensional
      finite difference solver that we developed, in which the distribution and
      evolution of the EPS and bacterial volume fractions are investigated. The
      hydrodynamic interaction between the biomass and the solvent flow field is also
      simulated in a shear cell environment, demonstrating the spatially and temporally
      heterogeneous distribution of the EPS and bacteria under shear. This model
      together with the numerical codes developed provides a predictive tool for
      studying biomass-flow interaction and other important biochemical interactions in
      the biofilm and solvent fluid mixture.

PMID- 22587125
TI  - Filling of a Poisson trap by a population of random intermittent searchers.
AB  - We extend the continuum theory of random intermittent search processes to the
      case of N independent searchers looking to deliver cargo to a single hidden
      target located somewhere on a semi-infinite track. Each searcher randomly
      switches between a stationary state and either a leftward or rightward constant
      velocity state. We assume that all of the particles start at one end of the track
      and realize sample trajectories independently generated from the same underlying
      stochastic process. The hidden target is treated as a partially absorbing trap in
      which a particle can only detect the target and deliver its cargo if it is
      stationary and within range of the target; the particle is removed from the
      system after delivering its cargo. As a further generalization of previous
      models, we assume that up to n successive particles can find the target and
      deliver its cargo. Assuming that the rate of target detection scales as 1/N, we
      show that there exists a well-defined mean-field limit N->infinity, in which the
      stochastic model reduces to a deterministic system of linear reaction-hyperbolic
      equations for the concentrations of particles in each of the internal states.
      These equations decouple from the stochastic process associated with filling the
      target with cargo. The latter can be modeled as a Poisson process in which the
      time-dependent rate of filling lambda(t) depends on the concentration of
      stationary particles within the target domain. Hence, we refer to the target as a
      Poisson trap. We analyze the efficiency of filling the Poisson trap with n
      particles in terms of the waiting time density f(n)(t). The latter is determined
      by the integrated Poisson rate MU(t)=?(0)(t)lambda(s)ds, which in turn depends on
      the solution to the reaction-hyperbolic equations. We obtain an approximate
      solution for the particle concentrations by reducing the system of reaction
      hyperbolic equations to a scalar advection-diffusion equation using a quasisteady
      state analysis. We compare our analytical results for the mean-field model with
      Monte Carlo simulations for finite N. We thus determine how the mean first
      passage time (MFPT) for filling the target depends on N and n.

PMID- 22587126
TI  - Temperature-modulated synchronization transition in coupled neuronal oscillators.
AB  - We study two firing properties to characterize the activities of a neuron:
      frequency-current (f-I) curves and phase response curves (PRCs), with variation
      in the intrinsic temperature scaling parameter (MU) controlling the opening and
      closing of ionic channels. We show a peak of the firing frequency for small MU in
      a class I neuron with the I value immediately after the saddle-node bifurcation,
      which is entirely different from previous experimental reports as well as model
      studies. The PRC takes a type II form on a logarithmic f-I curve when MU is
      small. Then, we analyze the synchronization phenomena in a two-neuron network
      using the phase-reduction method. We find common MU-dependent transition and
      bifurcation of synchronizations, regardless of the values of I. Such results give
      us helpful insight into synchronizations tuned with a sinusoidal-wave temperature
      modulation on neurons.

PMID- 22587127
TI  - Predator-prey dynamics in a uniform medium lead to directed percolation and wave
      train propagation.
AB  - The dynamics of birth-death processes with extinction points that are unstable in
      the deterministic average description has been extensively studied, mainly in the
      context of the stochastic transition from the mean-field attracting fixed point
      to the absorbing state. Here we study the opposite case of a small perturbation
      from the zero-population absorbing state. We show that such perturbations can
      grow beyond the mean-field attracting fixed point and then can collapse back into
      the absorbing state. Such dynamics can represent, for example, the fast growth of
      a pathogen and then its destruction by the immune system. We show that when the
      prey perturbation extinction probability is high, the loss of synchronization
      between the prey densities in different regions in space leads to two possible
      dynamic regimes: (a) a directed percolation regime based on the balance between
      regions escaping the absorbing state and regions absorbed into it, and (b) wave
      trains representing the transition of the entire space to the mean-field stable
      positive fixed point.

PMID- 22587129
TI  - Effective tension and fluctuations in active membranes.
AB  - We calculate the fluctuation spectrum of the shape of a lipid vesicle or cell
      exposed to a nonthermal source of noise. In particular, we take constraints on
      the membrane area and the volume of fluid that it encapsulates into account when
      obtaining expressions for the dependency of the membrane tension on the noise. We
      then investigate three possible origins of the nonthermal noise taken from the
      literature: A direct force, which models an external medium pushing on the
      membrane, a curvature force, which models a fluctuating spontaneous curvature,
      and a permeation force coming from an active transport of fluid through the
      membrane. For the direct force and curvature force cases, we compare our results
      to existing experiments on active membranes.

PMID- 22587128
TI  - Efficient coarse simulation of a growing avascular tumor.
AB  - The subject of this work is the development and implementation of algorithms
      which accelerate the simulation of early stage tumor growth models. Among the
      different computational approaches used for the simulation of tumor progression,
      discrete stochastic models (e.g., cellular automata) have been widely used to
      describe processes occurring at the cell and subcell scales (e.g., cell-cell
      interactions and signaling processes). To describe macroscopic characteristics
      (e.g., morphology) of growing tumors, large numbers of interacting cells must be
      simulated. However, the high computational demands of stochastic models make the
      simulation of large-scale systems impractical. Alternatively, continuum models,
      which can describe behavior at the tumor scale, often rely on phenomenological
      assumptions in place of rigorous upscaling of microscopic models. This limits
      their predictive power. In this work, we circumvent the derivation of closed
      macroscopic equations for the growing cancer cell populations; instead, we
      construct, based on the so-called "equation-free" framework, a computational
      superstructure, which wraps around the individual-based cell-level simulator and
      accelerates the computations required for the study of the long-time behavior of
      systems involving many interacting cells. The microscopic model, e.g., a cellular
      automaton, which simulates the evolution of cancer cell populations, is executed
      for relatively short time intervals, at the end of which coarse-scale information
      is obtained. These coarse variables evolve on slower time scales than each
      individual cell in the population, enabling the application of forward projection
      schemes, which extrapolate their values at later times. This technique is
      referred to as coarse projective integration. Increasing the ratio of projection
      times to microscopic simulator execution times enhances the computational
      savings. Crucial accuracy issues arising for growing tumors with radial symmetry
      are addressed by applying the coarse projective integration scheme in a
      cotraveling (cogrowing) frame. As a proof of principle, we demonstrate that the
      application of this scheme yields highly accurate solutions, while preserving the
      computational savings of coarse projective integration.

PMID- 22587130
TI  - Ion fluxes through nanopores and transmembrane channels.
AB  - We introduce an implicit solvent Molecular Dynamics approach for calculating
      ionic fluxes through narrow nanopores and transmembrane channels. The method
      relies on a dual-control-volume grand-canonical molecular dynamics (DCV-GCMD)
      simulation and the analytical solution for the electrostatic potential inside a
      cylindrical nanopore recently obtained by Levin [Europhys. Lett. 76, 163 (2006)].
      The theory is used to calculate the ionic fluxes through an artificial
      transmembrane channel which mimics the antibacterial gramicidin A channel. Both
      current-voltage and current-concentration relations are calculated under various
      experimental conditions. We show that our results are comparable to the
      characteristics associated to the gramicidin A pore, especially the existence of
      two binding sites inside the pore and the observed saturation in the current
      concentration profiles.

PMID- 22587131
TI  - Electroelastic unpinning of rotating vortices in biological excitable media.
AB  - Spiral waves in excitable biological media are associated with pathological
      situations. In the heart an action potential vortex pinned by an obstacle has to
      be removed through defibrillation protocols fine-tuned theoretically by using
      electrophysiological nonlinear mathematical models. Cardiac tissue, however, is
      an electroelastic medium whose electrical properties are strongly affected by
      large deformations. In this paper we specifically investigate the electroelastic
      pinning-unpinning mechanism in order to include cardiac contraction in the
      preexisting theoretically modeled defibrillation scenarios. Based on a two
      dimensional minimal electromechanical model, we show numerically the existence of
      an unpinning band characterized by the size of the obstacle, the pacing site, and
      the frequency. Similar numerical simulations, performed in the absence of elastic
      coupling, show small differences in comparison with the electroelastic studies,
      suggesting for this specific scenario of pinning-unpinning dynamics a
      nonprominent role of elasticity.

PMID- 22587132
TI  - Recurrent interactions in spiking networks with arbitrary topology.
AB  - The population activity of random networks of excitatory and inhibitory leaky
      integrate-and-fire neurons has been studied extensively. In particular, a state
      of asynchronous activity with low firing rates and low pairwise correlations
      emerges in sparsely connected networks. We apply linear response theory to
      evaluate the influence of detailed network structure on neuron dynamics. It turns
      out that pairwise correlations induced by direct and indirect network connections
      can be related to the matrix of direct linear interactions. Furthermore, we study
      the influence of the characteristics of the neuron model. Interpreting the reset
      as self-inhibition, we examine its influence, via the spectrum of single-neuron
      activity, on network autocorrelation functions and the overall correlation level.
      The neuron model also affects the form of interaction kernels and consequently
      the time-dependent correlation functions. We find that a linear instability of
      networks with Erdos-Renyi topology coincides with a global transition to a highly
      correlated network state. Our work shows that recurrent interactions have a
      profound impact on spike train statistics and provides tools to study the effects
      of specific network topologies.

PMID- 22587133
TI  - Frequency-dependent signal transfer at the interface between electrogenic cells
      and nanocavity electrodes.
AB  - We present a model to describe the response of chip-based nanocavity sensors
      during extracellular recording of action potentials. These sensors feature
      microelectrodes which are embedded in liquid-filled cavities. They can be used
      for the highly localized detection of electrical signals on a chip. We calculate
      the sensor's impedance and simulate the propagation of action potentials.
      Subsequently we apply our findings to analyze cell-chip coupling properties. The
      results are compared to experimental data obtained from cardiomyocyte-like cells.
      We show that both the impedance and the modeled action potentials fit the
      experimental data well. Furthermore, we find evidence for a large seal resistance
      of cardiomyocytes on nanocavity sensors compared to conventional planar recording
      systems.

PMID- 22587134
TI  - Network reciprocity by coexisting learning and teaching strategies.
AB  - We propose a network reciprocity model in which an agent probabilistically adopts
      learning or teaching strategies. In the learning adaptation mechanism, an agent
      may copy a neighbor's strategy through Fermi pairwise comparison. The teaching
      adaptation mechanism involves an agent imposing its strategy on a neighbor. Our
      simulations reveal that the reciprocity is significantly affected by the
      frequency with which learning and teaching agents coexist in a network and by the
      structure of the network itself.

PMID- 22587135
TI  - Escape rate of an active Brownian particle over a potential barrier.
AB  - We study the dynamics of an active Brownian particle with a nonlinear friction
      function located in a spatial cubic potential. For strong but finite damping, the
      escape rate of the particle over the spatial potential barrier shows a
      nonmonotonic dependence on the noise intensity. We relate this behavior to the
      fact that the active particle escapes from a limit cycle rather than from a fixed
      point and that a certain amount of noise can stabilize the sojourn of the
      particle on this limit cycle.

PMID- 22587136
TI  - Critical condition of the water-retention model.
AB  - We study how much water can be retained without leaking through boundaries when
      each unit square of a two-dimensional lattice is randomly assigned a block of
      unit bottom area but with different heights from zero to n-1. As more blocks are
      put into the system, there exists a phase transition beyond which the system
      retains a macroscopic volume of water. We locate the critical points and verify
      that the criticality belongs to the two-dimensional percolation universality
      class. If the height distribution can be approximated as continuous for large n,
      the system is always close to a critical point and the fraction of the area below
      the resulting water level is given by the percolation threshold. This provides a
      universal upper bound of areas that can be covered by water in a random
      landscape.

PMID- 22587137
TI  - Shape evolution of a core-shell spherical particle under hydrostatic pressure.
AB  - The morphological evolution by surface diffusion of a core-shell spherical
      particle has been investigated theoretically under hydrostatic pressure when the
      shear modulii of the core and shell are different. A linear stability analysis
      has demonstrated that depending on the pressure, shear modulii, and radii of both
      phases, the free surface of the composite particle may be unstable with respect
      to a shape perturbation. A stability diagram finally emphasizes that the
      roughness development is favored in the case of a hard shell with a soft core.

PMID- 22587138
TI  - Comment on "Inference with minimal Gibbs free energy in information field
      theory".
AB  - Enbetalin and Weig [Phys. Rev. E 82, 051112 (2010)] have introduced a "minimum
      Gibbs free energy" (MGFE) approach for estimation of the mean signal and signal
      uncertainty in Bayesian inference problems: it aims to combine the maximum a
      posteriori (MAP) and maximum entropy (ME) principles. We point out, however, that
      there are some important questions to be clarified before the new approach can be
      considered fully justified, and therefore able to be used with confidence. In
      particular, after obtaining a Gaussian approximation to the posterior in terms of
      the MGFE at some temperature T, this approximation should always be raised to the
      power of T to yield a reliable estimate. In addition, we show explicitly that
      MGFE indeed incorporates the MAP principle, as well as the MDI (minimum
      discrimination information) approach, but not the well-known ME principle of
      Jaynes [E.T. Jaynes, Phys. Rev. 106, 620 (1957)]. We also illuminate some related
      issues and resolve apparent discrepancies. Finally, we investigate the
      performance of MGFE estimation for different values of T, and we discuss the
      advantages and shortcomings of the approach.

PMID- 22587140
TI  - Symmetry-induced pinning-depinning transition of a subharmonic wave pattern.
AB  - The stationary to drifting transition of a subharmonic wave pattern is studied in
      the presence of inhomogeneities and drift forces as the pattern wavelength is
      comparable with the system size. We consider a pinning-depinning transition of
      stationary subharmonic waves in a tilted quasi-one-dimensional fluidized shallow
      granular bed driven by a periodic air flow in a small cell. The transition is
      mediated by the competition of the inherent periodicity of the subharmonic
      pattern, the asymmetry of the system, and the finite size of the cell.
      Measurements of the mean phase velocity of the subharmonic pattern are in good
      agreement with those inferred from an amplitude equation, which takes into
      account asymmetry and finite-size effects of the system, emphasizing the main
      ingredients and mechanism of the transition.

PMID- 22587141
TI  - How to obtain extreme multistability in coupled dynamical systems.
AB  - We present a method for designing an appropriate coupling scheme for two
      dynamical systems in order to realize extreme multistability. We achieve the
      coexistence of infinitely many attractors for a given set of parameters by using
      the concept of partial synchronization based on Lyapunov function stability. We
      show that the method is very general and allows a great flexibility in choosing
      the coupling. Furthermore, we demonstrate its applicability in different models,
      such as the Rossler system and a chemical oscillator. Finally we show that
      extreme multistability is robust with respect to parameter mismatch and, hence, a
      very general phenomenon in coupled systems.

PMID- 22587142
TI  - Determination of carrier-envelope phase of relativistic few-cycle laser pulses by
      Thomson backscattering spectroscopy.
AB  - A method is proposed to determine the carrier-envelope phase (CEP) of a
      relativistic few-cycle laser pulse via the frequency of the Thomson
      backscattering (TBS) light. We theoretically investigate the generation of a
      flying mirror when a few-cycle drive pulse with relativistic intensity interacts
      with a target combined with a thin and a thick foil. The frequency of the TBS
      light generated from the flying mirror shows a sensitive dependence on the CEP of
      the drive pulse. The obtained results are verified by one-dimensional particle-in
      cell simulations and are explained by an analytical model.

PMID- 22587143
TI  - Removing spurious interactions in complex networks.
AB  - Identifying and removing spurious links in complex networks is meaningful for
      many real applications and is crucial for improving the reliability of network
      data, which, in turn, can lead to a better understanding of the highly
      interconnected nature of various social, biological, and communication systems.
      In this paper, we study the features of different simple spurious link
      elimination methods, revealing that they may lead to the distortion of networks'
      structural and dynamical properties. Accordingly, we propose a hybrid method that
      combines similarity-based index and edge-betweenness centrality. We show that our
      method can effectively eliminate the spurious interactions while leaving the
      network connected and preserving the network's functionalities.

PMID- 22587144
TI  - Hysteresis effects of changing the parameters of noncooperative games.
AB  - We adapt the method used by Jaynes to derive the equilibria of statistical
      physics to instead derive equilibria of bounded rational game theory. We analyze
      the dependence of these equilibria on the parameters of the underlying game,
      focusing on hysteresis effects. In particular, we show that by gradually imposing
      individual-specific tax rates on the players of the game, and then gradually
      removing those taxes, the players move from a poor equilibrium to one that is
      better for all of them.

PMID- 22587145
TI  - Agent-specific impact of single trades in financial markets.
AB  - We present an analysis of the price impact associated with single trades effected
      by different financial firms. Using data from the Spanish Stock Market, we find a
      high degree of heterogeneity across different market members, both in the
      instantaneous impact functions and in the time-dependent market response to
      trades by individual members. This heterogeneity is statistically incompatible
      with the existence of market-wide universal impact dynamics that apply uniformly
      to all trades and suggest that, rather, market dynamics emerge from the complex
      interaction of different behaviors of market participants. Several possible
      reasons for this are discussed, along with potential extensions one may consider
      to increase the range of applicability of existing models of market impact.

PMID- 22587146
TI  - Topological effects on dynamics in complex pulse-coupled networks of integrate
      and-fire type.
AB  - For a class of integrate-and-fire, pulse-coupled networks with complex topology,
      we study the dependence of the pulse rate on the underlying architectural
      connectivity statistics. We derive the distribution of the pulse rate from this
      dependence and determine when the underlying scale-free architectural
      connectivity gives rise to a scale-free pulse-rate distribution. We identify the
      scaling of the pairwise coupling between the dynamical units in this network
      class that keeps their pulse rates bounded in the infinite-network limit. In the
      process, we determine the connectivity statistics for a specific scale-free
      network grown by preferential attachment.

PMID- 22587147
TI  - Effective number of accessed nodes in complex networks.
AB  - The measurement called accessibility has been proposed as a means to quantify the
      efficiency of the communication between nodes in complex networks. This article
      reports results regarding the properties of accessibility, including its
      relationship with the average minimal time to visit all nodes reachable after h
      steps along a random walk starting from a source, as well as the number of nodes
      that are visited after a finite period of time. We characterize the relationship
      between accessibility and the average number of walks required in order to visit
      all reachable nodes (the exploration time), conjecture that the maximum
      accessibility implies the minimal exploration time, and confirm the relationship
      between the accessibility values and the number of nodes visited after a basic
      time unit. The latter relationship is investigated with respect to three types of
      dynamics: traditional random walks, self-avoiding random walks, and preferential
      random walks.

PMID- 22587148
TI  - Spreading paths in partially observed social networks.
AB  - Understanding how and how far information, behaviors, or pathogens spread in
      social networks is an important problem, having implications for both predicting
      the size of epidemics, as well as for planning effective interventions. There
      are, however, two main challenges for inferring spreading paths in real-world
      networks. One is the practical difficulty of observing a dynamic process on a
      network, and the other is the typical constraint of only partially observing a
      network. Using static, structurally realistic social networks as platforms for
      simulations, we juxtapose three distinct paths: (1) the stochastic path taken by
      a simulated spreading process from source to target; (2) the topologically
      shortest path in the fully observed network, and hence the single most likely
      stochastic path, between the two nodes; and (3) the topologically shortest path
      in a partially observed network. In a sampled network, how closely does the
      partially observed shortest path (3) emulate the unobserved spreading path (1)?
      Although partial observation inflates the length of the shortest path, the
      stochastic nature of the spreading process also frequently derails the dynamic
      path from the shortest path. We find that the partially observed shortest path
      does not necessarily give an inflated estimate of the length of the process path;
      in fact, partial observation may, counterintuitively, make the path seem shorter
      than it actually is.

PMID- 22587149
TI  - Epidemic reemergence in adaptive complex networks.
AB  - The dynamic nature of a system gives rise to dynamical features of epidemic
      spreading, such as oscillation and bistability. In this paper, by studying the
      epidemic spreading in growing networks, in which susceptible nodes may adaptively
      break the connections with infected ones yet avoid being isolated, we reveal a
      phenomenon, epidemic reemergence, where the number of infected nodes is incubated
      at a low level for a long time and then erupts for a short time. The process may
      repeat several times before the infection finally vanishes. Simulation results
      show that all three factors, namely the network growth, the connection breaking,
      and the isolation avoidance, are necessary for epidemic reemergence to happen. We
      present a simple theoretical analysis to explain the process of reemergence in
      detail. Our study may offer some useful insights, helping explain the phenomenon
      of repeated epidemic explosions.

PMID- 22587150
TI  - Intermittent social distancing strategy for epidemic control.
AB  - We study the critical effect of an intermittent social distancing strategy on the
      propagation of epidemics in adaptive complex networks. We characterize the effect
      of our strategy in the framework of the susceptible-infected-recovered model. In
      our model, based on local information, a susceptible individual interrupts the
      contact with an infected individual with a probability sigma and restores it
      after a fixed time t(b). We find that, depending on the network topology, in our
      social distancing strategy there exists a cutoff threshold sigma(c) beyond which
      the epidemic phase disappears. Our results are supported by a theoretical
      framework and extensive simulations of the model. Furthermore we show that this
      strategy is very efficient because it leads to a "susceptible herd behavior" that
      protects a large fraction of susceptible individuals. We explain our results
      using percolation arguments.

PMID- 22587152
TI  - Complexity of spatiotemporal traffic phenomena in flow of identical drivers:
      explanation based on fundamental hypothesis of three-phase theory.
AB  - Based on numerical simulations of a stochastic three-phase traffic flow model, we
      reveal the physics of the fundamental hypothesis of three-phase theory that, in
      contrast with a fundamental diagram of classical traffic flow theories,
      postulates the existence of a two-dimensional (2D) region of steady states of
      synchronized flow where a driver makes an arbitrary choice of a space gap (time
      headway) to the preceding vehicle. We find that macroscopic and microscopic
      spatiotemporal effects of the entire complexity of traffic congestion observed up
      to now in real measured traffic data can be explained by simulations of traffic
      flow consisting of identical drivers and vehicles, if a microscopic model used in
      these simulations incorporates the fundamental hypothesis of three-phase theory.
      It is shown that the driver's choice of space gaps within the 2D region of
      synchronized flow associated with the fundamental hypothesis of three-phase
      theory can qualitatively change types of congested patterns that can emerge at a
      highway bottleneck. In particular, if drivers choose long enough spaces gaps
      associated with the fundamental hypothesis, then general patterns, which consist
      of synchronized flow and wide moving jams, do not emerge independent of the flow
      rates and bottleneck characteristics: Even at a heavy bottleneck leading to a
      very low speed within congested patterns, only synchronized flow patterns occur
      in which no wide moving jams emerge spontaneously.

PMID- 22587151
TI  - Effects of degree-biased transmission rate and nonlinear infectivity on rumor
      spreading in complex social networks.
AB  - We introduce a generalized rumor spreading model and analytically investigate the
      spreading of rumors on scale-free (SF) networks. In the standard rumor spreading
      model, each node has an infectivity equal to its degree, and connectivity is
      uniform across all links. To generalize this model, we introduce an infectivity
      function that determines the number of simultaneous contacts that a given node
      (individual) may establish with its connected neighbors and a connectivity
      strength function (CSF) for the direct link between two connected nodes. These
      lead to a degree-biased propagation of rumors. For nonlinear functions, this
      generalization is reflected in the infectivity's exponent alpha and the CSF's
      exponent beta. We show that, by adjusting exponents alpha and beta, the epidemic
      threshold can be controlled. This feature is absent in the standard rumor
      spreading model. In addition, we obtain a critical threshold. We show that the
      critical threshold for our generalized model is greater than that of the standard
      model on a finite SF network. Theoretically, we show that beta=-1 leads to a
      maximum spreading of rumors, and computation results on different networks verify
      our theoretical prediction. Also, we show that a smaller alpha leads to a larger
      spreading of rumors. Our results are interesting since we obtain these results
      regardless of the network topology and configuration.

PMID- 22587153
TI  - Properties of pedestrians walking in line: fundamental diagrams.
AB  - We present experimental results obtained for a one-dimensional pedestrian flow
      using high precision motion capture. The full pedestrians' trajectories are
      obtained. In this paper, we focus on the fundamental diagram, and on the relation
      between the instantaneous velocity and spatial headway (distance to the
      predecessor). While the latter was found to be linear in previous experiments, we
      show that it is rather a piecewise linear behavior which is found if larger
      density ranges are covered. Indeed, our data clearly exhibits three distinct
      regimes in the behavior of pedestrians that follow each other. The transitions
      between these regimes occur at spatial headways of about 1.1 and 3 m,
      respectively. This finding could be useful for future modeling.

PMID- 22587154
TI  - Extracting topological features from dynamical measures in networks of Kuramoto
      oscillators.
AB  - The Kuramoto model for an ensemble of coupled oscillators provides a paradigmatic
      example of nonequilibrium transitions between an incoherent and a synchronized
      state. Here we analyze populations of almost identical oscillators in arbitrary
      interaction networks. Our aim is to extract topological features of the
      connectivity pattern from purely dynamical measures based on the fact that in a
      heterogeneous network the global dynamics is not only affected by the
      distribution of the natural frequencies but also by the location of the different
      values. In order to perform a quantitative study we focused on a very simple
      frequency distribution considering that all the frequencies are equal but one,
      that of the pacemaker node. We then analyze the dynamical behavior of the system
      at the transition point and slightly above it as well as very far from the
      critical point, when it is in a highly incoherent state. The gathered topological
      information ranges from local features, such as the single-node connectivity, to
      the hierarchical structure of functional clusters and even to the entire
      adjacency matrix.

PMID- 22587155
TI  - Single-shooting homotopy method for parameter identification in dynamical
      systems.
AB  - An algorithm for identifying parameters in dynamical systems is developed in this
      work using homotopy transformations and the single-shooting method. The equations
      governing the dynamics of the mathematical model are augmented with observer-like
      homotopy terms that smooth the objective function. As a result, premature
      convergence to a local minimum is avoided and the obtained parameter estimates
      are globally optimal. Numerical examples are presented to demonstrate the
      application of the proposed approach to chaotic systems.

PMID- 22587156
TI  - Supersharp resonances in chaotic wave scattering.
AB  - Wave scattering in chaotic systems can be characterized by its spectrum of
      resonances, z(n)=E(n)-iGamma(n)/2, where E(n) is related to the energy and
      Gamma(n) is the decay rate or width of the resonance. If the corresponding ray
      dynamics is chaotic, a gap is believed to develop in the large-energy limit:
      almost all Gamma(n) become larger than some gamma. However, rare cases with
      Gamma<gamma may be present and actually dominate scattering events. We consider
      the statistical properties of these supersharp resonances. We find that their
      number does not follow the fractal Weyl law conjectured for the bulk of the
      spectrum. We also test, for a simple model, the universal predictions of random
      matrix theory for density of states inside the gap and the hereby derived
      probability distribution of gap size.

PMID- 22587157
TI  - Short periodic orbit approach to resonances and the fractal Weyl law.
AB  - We investigate the properties of the semiclassical short periodic orbit approach
      for the study of open quantum maps that was recently introduced [Novaes, Pedrosa,
      Wisniacki, Carlo, and Keating, Phys. Rev. E 80, 035202(R) (2009)]. We provide
      solid numerical evidence, for the paradigmatic systems of the open baker and cat
      maps, that by using this approach the dimensionality of the eigenvalue problem is
      reduced according to the fractal Weyl law. The method also reproduces the
      projectors |psi(n)(R)><psi(n)(L)|, which involves the right and left states
      associated with a given eigenvalue and is supported on the classical phase-space
      repeller.

PMID- 22587158
TI  - Required criteria for recognizing new types of chaos: application to the "cord"
      attractor.
AB  - After suggesting criteria to recognize a new system and a new attractor-and to
      make a distinction between them-the paper details the topological analysis of the
      "cord" attractor. This attractor, which resembles a cord between two leaves, is
      produced by a three-dimensional system that is obtained after a modification of
      the Lorenz-84 model for the global atmospheric circulation [L. A. Aguirre and C.
      Letellier, Phys. Rev. E 83, 066209 (2011)]. The nontrivial topology of the
      attractor is described in terms of a template that corresponds to a reverse
      horseshoe, that is, to a spiral Rossler attractor with negative and positive
      global pi twists. Due to its particular structure and to the fact that such a
      system has two variables from which the dynamics is poorly observable, this
      attractor qualifies as a challenging benchmark in nonlinear dynamics.

PMID- 22587159
TI  - Fidelity for kicked atoms with gravity near a quantum resonance.
AB  - Kicked atoms under a constant Stark or gravity field are investigated for
      experimental setups with cold and ultracold atoms. The parametric stability of
      the quantum dynamics is studied using the fidelity. In the case of a quantum
      resonance, it is shown that the behavior of the fidelity depends on arithmetic
      properties of the gravity parameter. Close to a quantum resonance, the long-time
      asymptotics of the fidelity is studied by means of a pseudoclassical
      approximation introduced by Fishman et al. [J. Stat. Phys. 110, 911 (2003)]. The
      long-time decay of fidelity arises from the tunneling out of pseudoclassical
      stable islands, and a simple ansatz is proposed which satisfactorily reproduces
      the main features observed in numerical simulations.

PMID- 22587160
TI  - Heat diffusion: thermodynamic depth complexity of networks.
AB  - In this paper we use the Birkhoff-von Neumann decomposition of the diffusion
      kernel to compute a polytopal measure of graph complexity. We decompose the
      diffusion kernel into a series of weighted Birkhoff combinations and compute the
      entropy associated with the weighting proportions (polytopal complexity). The
      maximum entropy Birkhoff combination can be expressed in terms of matrix
      permanents. This allows us to introduce a phase-transition principle that links
      our definition of polytopal complexity to the heat flowing through the network at
      a given diffusion time. The result is an efficiently computed complexity measure,
      which we refer to as flow complexity. Moreover, the flow complexity measure
      allows us to analyze graphs and networks in terms of the thermodynamic depth. We
      compare our method with three alternative methods described in the literature
      (Estrada's heterogeneity index, the Laplacian energy, and the von Neumann
      entropy). Our study is based on 217 protein-protein interaction (PPI) networks
      including histidine kinases from several species of bacteria. We find a
      correlation between structural complexity and phylogeny (more evolved species
      have statistically more complex PPIs). Although our methods outperform the
      alternatives, we find similarities with Estrada's heterogeneity index in terms of
      network size independence and predictive power.

PMID- 22587161
TI  - Intermingled basins in coupled Lorenz systems.
AB  - We consider a system of two identical linearly coupled Lorenz oscillators
      presenting synchronization of chaotic motion for a specified range of the
      coupling strength. We verify the existence of global synchronization and
      antisynchronization attractors with intermingled basins of attraction such that
      the basin of one attractor is riddled with holes belonging to the basin of the
      other attractor and vice versa. We investigated this phenomenon by verifying the
      fulfillment of the mathematical requirements for intermingled basins and obtained
      scaling laws that characterize quantitatively the riddling of both basins in this
      system.

PMID- 22587163
TI  - Onset of chaos and relaxation in isolated systems of interacting spins: energy
      shell approach.
AB  - We study the onset of chaos and statistical relaxation in two isolated dynamical
      quantum systems of interacting spins 1/2, one of which is integrable and the
      other chaotic. Our approach to identifying the emergence of chaos is based on the
      level of delocalization of the eigenstates with respect to the energy shell, the
      latter being determined by the interaction strength between particles or
      quasiparticles. We also discuss how the onset of chaos may be anticipated by a
      careful analysis of the Hamiltonian matrices, even before diagonalization. We
      find that despite differences between the two models, their relaxation processes
      following a quench are very similar and can be described analytically with a
      theory previously developed for systems with two-body random interactions. Our
      results imply that global features of statistical relaxation depend on the degree
      of spread of the eigenstates within the energy shell and may happen to both
      integrable and nonintegrable systems.

PMID- 22587162
TI  - Classical dynamics of quantum entanglement.
AB  - We analyze numerically the dynamical generation of quantum entanglement in a
      system of two interacting particles, started in a coherent separable state, for
      decreasing values of h. As h->0 the entanglement entropy, computed at any finite
      time, converges to a finite nonzero value. The limit law that rules the time
      dependence of entropy is well reproduced by purely classical computations. Its
      general features can be explained by simple classical arguments, which expose the
      different ways entanglement is generated in systems that are classically chaotic
      or regular.

PMID- 22587164
TI  - Stationary patterns of coherence and incoherence in two-dimensional arrays of non
      locally-coupled phase oscillators.
AB  - Recently, it has been shown that large arrays of identical oscillators with
      nonlocal coupling can have a remarkable type of solutions that display a
      stationary macroscopic pattern of coexisting regions with coherent and incoherent
      motions, often called chimera states. Here, we present a detailed numerical study
      of the appearance of such solutions in two-dimensional arrays of coupled phase
      oscillators. We discover a variety of stationary patterns, including circular
      spots, stripe patterns, and patterns of multiple spirals. Here, stationarity
      means that, for increasing system size, the locally averaged phase distributions
      tend to the stationary profile given by the corresponding thermodynamic limit
      equation.

PMID- 22587165
TI  - Quantum mechanical calculation of spectral statistics of a modified Kepler
      problem.
AB  - For a modified Kepler problem, we reexamine jumps in the saturation spectral
      rigidity and large oscillations of the level number variance with near zero
      minima. Earlier discrepancy between the periodic orbit theory and numerical
      calculation is cleared by a quantum mechanical calculation. A new class of radial
      periodic orbits is included establishing a complete correspondence between the
      periodic orbit theory and the quantum mechanical approach. We show that the
      diagonal approximation for the level density in the periodic orbit theory already
      gives a good fit with the numerical calculation. Even greater accuracy is
      achieved by considering coherent interference between the classical periodic
      orbits term and the Balian-Bloch term. This procedure produces improved results
      for the hard-wall rectangular billiards as well.

PMID- 22587166
TI  - Mode-resolved travel-time statistics for elastic rays in three-dimensional
      billiards.
AB  - We consider the ray limit of propagating ultrasound waves in three-dimensional
      bodies made from a homogeneous, isotropic, elastic material. Using a Monte Carlo
      approach, we simulate the propagation and proliferation of elastic rays using
      realistic angle-dependent reflection coefficients, taking into account mode
      conversion and ray splitting. For a few simple geometries, we analyze the long
      time equilibrium distribution, focusing on the energy ratio between compressional
      and shear waves. Finally, we study the travel time statistics, i.e., the
      distribution of the amount of time a given trajectory spends as a compressional
      wave, as compared to the total travel time. These results are intimately related
      to recent elastodynamics experiments on Coda-wave interferometry by Lobkis and
      Weaver [Phys. Rev. E 78, 066212 (2008)].

PMID- 22587167
TI  - Consequences of flooding on spectral statistics.
AB  - We study spectral statistics in systems with a mixed phase space, in which
      regions of regular and chaotic motion coexist. Increasing their density of
      states, we observe a transition of the level-spacing distribution P(s) from Berry
      Robnik to Wigner statistics, although the underlying classical phase-space
      structure and the effective Planck constant h(eff) remain unchanged. This
      transition is induced by flooding, i.e., the disappearance of regular states due
      to increasing regular-to-chaotic couplings. We account for this effect by a
      flooding-improved Berry-Robnik distribution, in which an effectively reduced size
      of the regular island enters. To additionally describe power-law level repulsion
      at small spacings, we extend this prediction by explicitly considering the
      tunneling couplings between regular and chaotic states. This results in a
      flooding- and tunneling-improved Berry-Robnik distribution which is in excellent
      agreement with numerical data.

PMID- 22587168
TI  - Spikes matter for phase-locked bursting in inhibitory neurons.
AB  - We show that inhibitory networks composed of two endogenously bursting neurons
      can robustly display several coexistent phase-locked states in addition to stable
      antiphase and in-phase bursting. This work complements and enhances our recent
      result [Jalil, Belykh, and Shilnikov, Phys. Rev. E 81, 045201(R) (2010)] that
      fast reciprocal inhibition can synchronize bursting neurons due to spike
      interactions. We reveal the role of spikes in generating multiple phase-locked
      states and demonstrate that this multistability is generic by analyzing diverse
      models of bursting networks with various fast inhibitory synapses; the individual
      cell models include the reduced leech heart interneuron, the Sherman model for
      pancreatic beta cells, and the Purkinje neuron model.

PMID- 22587169
TI  - Reflection-antisymmetric spatiotemporal chaos under field-translational
      invariance.
AB  - We propose a route to spatiotemporal chaos, in which the system is assumed to
      have spatial reflection antisymmetry and field-translation symmetry. The lowest
      order nonlinear equation that satisfies these symmetries is explored with the
      weak nonlinear analysis around the bifurcation point. We conclude that the
      nonlinear term ?(x)(2)u?(x)(3)u is important to make a nontrivial dynamics, and
      show that the nonlinear dynamical equation having this term produces a turbulent
      dynamics.

PMID- 22587170
TI  - Random dynamical models from time series.
AB  - In this work we formulate a consistent Bayesian approach to modeling stochastic
      (random) dynamical systems by time series and implement it by means of artificial
      neural networks. The feasibility of this approach for both creating models
      adequately reproducing the observed stationary regime of system evolution, and
      predicting changes in qualitative behavior of a weakly nonautonomous stochastic
      system, is demonstrated on model examples. In particular, a successful prognosis
      of stochastic system behavior as compared to the observed one is illustrated on
      model examples, including discrete maps disturbed by non-Gaussian and nonuniform
      noise and a flow system with Langevin force.

PMID- 22587171
TI  - Time-periodic lattice of spiral pairs in excitable media.
AB  - The feasibility of a spiral-type solution, periodic both in time and in space, of
      a reaction-diffusion equation (specifically the FitzHugh-Nagumo system) in an
      excitable medium is numerically demonstrated. The solution consists of arrays of
      interacting spiral pairs, which repeatedly create by partial annihilation a
      system of residual portions (RPs). The latter behaves as a source to the next
      generation of the spiral-pair array. If basic (highest) translational symmetry is
      not conserved, pointwise perturbations, above a certain threshold, are shown to
      be able to destroy the pattern after a certain transient time by changing its
      symmetry. If the basic translational symmetry is preserved, such perturbations do
      not cause destruction unless occurring at the nearest vicinity of the RP site.
      Singular value decomposition methods are used to analyze the structure of the
      pattern, revealing the importance of the spiral pairs and the RPs.

PMID- 22587172
TI  - Temperature crossover of decoherence rates in chaotic and regular bath dynamics.
AB  - The effect of chaotic bath dynamics on the decoherence of a quantum system is
      examined for the vibrational degrees of freedom of a diatomic molecule in a
      realistic, constant temperature collisional bath. As an example, the specific
      case of I(2) in liquid xenon is examined as a function of temperature, and the
      results compared with an integrable xenon bath. A crossover in behavior is found:
      The integrable bath induces more decoherence at low bath temperatures than does
      the chaotic bath, whereas the opposite is the case at the higher bath
      temperatures. These results, verifying a conjecture due to Wilkie, shed light on
      the differing views of the effect of chaotic dynamics on system decoherence.

PMID- 22587173
TI  - Emergence and multistability of time-periodic states in a population of noisy
      passive rotators with time-lag coupling.
AB  - We study the onset of the time-periodic distribution of phases in a population of
      a large number of passive rotators in asymmetric potential and time-delayed
      antiferromagnetic mean-field coupling. The threshold between the stationary and
      the time-periodic states is found exactly by solving the linearized Fokker-Planck
      equation using the numerical continuation technique. A typical scenario of the
      reversal of the left- and right-running phases by the asymmetric potential is
      demonstrated. Analytical results are supported by numerical simulations of the
      Langevin equations.

PMID- 22587174
TI  - Bistability and chaos in the Taylor-Green dynamo.
AB  - Using direct numerical simulations, we study dynamo action under Taylor-Green
      forcing for a magnetic Prandtl number of 0.5. We observe bistability with weak-
      and strong-magnetic-field branches. Both the dynamo branches undergo subcritical
      dynamo transition. We also observe a host of dynamo states including constant,
      periodic, quasiperiodic, and chaotic magnetic fields. One of the chaotic states
      originates through a quasiperiodic route with phase locking, while the other
      chaotic attractor appears to follow the Newhouse-Ruelle-Takens route to chaos. We
      also observe intermittent transitions between quasiperiodic and chaotic states
      for a given Taylor-Green forcing.

PMID- 22587175
TI  - Bilateral shear layer between two parallel Couette flows.
AB  - We consider an unusual shear layer occuring between two parallel Couette flows.
      Contrary to the classical free shear layer, the width of the shear zone does not
      vary in the streamwise direction but rather exhibits a lateral variation. Based
      on some simplifying assumptions, an analytic solution is derived for this shear
      layer. These assumptions are justified by a comparison with numerical solutions
      of the full Navier-Stokes equations, which accord with the analytical solution to
      better than 1% in the entire domain. An explicit formula is found for the width
      of the shear zone as a function of the wall-normal coordinate. This width is
      independent of the wall velocities in the laminar regime. Preliminary results for
      a cocurrent laminar-turbulent shear layer in the same geometry are also
      presented. Shear-layer instabilities are then developed and result in an unsteady
      mixing zone at the interface between the two cocurrent streams.

PMID- 22587176
TI  - Buoyancy-driven convection may switch between reactive states in three
      dimensional chemical waves.
AB  - Traveling waves in an extended reactor, whose width cannot be neglected,
      represent a three-dimensional (3D) reaction-diffusion-convection system. We
      investigate the effects of buoyancy-driven convection in such a setting. The 3D
      waves traveled through horizontal layers of the iodate-arsenous acid (IAA)
      reaction solution containing excess of arsenous acid. The depth of the reaction
      solution was the examined parameter. An increase in the intensity of buoyancy
      driven flow caused an increase of the traveling wave velocities. Convection
      distorted the front of the chemical waves. For layers deeper than h>13 mm, heat
      release became smaller than heat production causing the emergence of Rayleigh
      Benard convection cells. At the interface, a dependency of wave shape on solution
      depth was observed. For h<7 mm, the waves adopted a stable V-like shape, while
      for h>13 mm a parabolic shape dominated. For 7<h<13 mm, both shapes were realized
      with the same probability. Finally, an intermittent switch between stoichiometric
      regimes is observed as an unexpected effect of the buoyancy-driven convection.
      The switch is expressed by iodine enrichment in the product. Hence, the
      experiments demonstrate that the buoyancy-driven convective flow can cause long
      lived, but nevertheless transient, changes in the chemical composition by
      inducing a local transition between different regimes of the IAA reaction.

PMID- 22587178
TI  - Numerical study on the bulk instability of constant-current conduction in cation
      exchange membranes.
AB  - Numerical simulation of two-dimensional bulk instability of the one-dimensional
      conduction state in an electrolyte confined between a pair of cation-exchange
      membranes subjected to an external voltage is conducted under an assumption of
      constant current. By employing variable grids, we resolve the problem of
      sensitive dependence of the numerical solutions to the grid refinement in
      particular at a current close to the limiting value. In fact, the full range of
      parameters, i.e., Schmidt number, Peclet number, diffusivity ratio, and current,
      is considered in this study in obtaining the stability chart. It turns out that
      the Schmidt number exerts almost no influence on the results. From the neutral
      curves in the chart of the parameter space (current versus diffusivity ratio,
      i.e., cation diffusivity divided by anion diffusivity) we confirm that the system
      tends to be unstable at high Peclet numbers, high currents, and low diffusivity
      ratios. As the diffusivity ratio is increased the instability mode switches from
      the monotonic to the oscillatory type, and the critical diffusivity ratio for the
      switching is found to be decreased as the Peclet number decreases. At the
      switching, no jump in the neutral curves is found, contrary to the earlier
      result, because the wave number is set free to change in this study. The
      stability chart obtained in this study represents the true boundaries in
      discriminating the stable from the unstable parameter sets because the critical
      eigenvalues constituting the chart are sought for the entire possible range of
      the wave numbers and the frequencies.

PMID- 22587177
TI  - Low-Reynolds-number swimming in viscous two-phase fluids.
AB  - The fluid media surrounding many microorganisms are often mixtures of multiple
      materials with very different physical properties. The composition and rheology
      of the mixture may strongly affect the related locomotive behaviors. We study the
      classical Taylor's swimming sheet problem within a two-fluid model, which
      consists of two intermixed viscous fluids with different viscosities, with both
      numerical experiments and analysis. Our results indicate that both the swimming
      speed and efficiency may be decreased substantially relative to those for a
      single-phase fluid.

PMID- 22587179
TI  - Vortex knots in a Bose-Einstein condensate.
AB  - We present a method for numerically building a vortex knot state in the
      superfluid wave function of a Bose-Einstein condensate. We integrate in time the
      governing Gross-Pitaevskii equation to determine evolution and shape preservation
      of the two (topologically) simplest vortex knots which can be wrapped over a
      torus. We find that the velocity of a vortex knot depends on the ratio of
      poloidal and toroidal radius: for smaller ratio, the knot travels faster.
      Finally, we show how vortex knots break up into vortex rings.

PMID- 22587180
TI  - Fluid-mechanical interaction of flexible bacterial flagella by the immersed
      boundary method.
AB  - Flagellar bundling is an important aspect of locomotion in bacteria such as
      Escherichia coli. To study the hydrodynamic behavior of helical flagella, we
      present a computational model that is based on the geometry of the bacterial
      flagellar filament at the micrometer scale. We consider two model flagella, each
      of which has a rotary motor at its base with the rotation rate of the motor set
      at 100 Hz. Bundling occurs when both flagella are left-handed helices turning
      counterclockwise (when viewed from the nonmotor end of the flagellum looking back
      toward the motor) or when both flagella are right-handed helices turning
      clockwise. Helical flagella of the other combinations of handedness and rotation
      direction do not bundle.

PMID- 22587181
TI  - Control of particle clustering in turbulence by polymer additives.
AB  - We study the clustering properties of inertial particles in a turbulent
      viscoelastic fluid. The investigation is carried out by means of direct numerical
      simulations of turbulence in the Oldroyd-B model. The effects of polymers on the
      small-scale properties of homogeneous turbulence are considered in relation with
      their consequences on clustering of particles, both lighter and heavier than the
      carrying fluid. We show that, depending on particle and flow parameters, polymers
      can either increase or decrease clustering.

PMID- 22587182
TI  - First-order energy-integral model for thin Newtonian liquids falling along
      sinusoidal furrows.
AB  - An average modeling methodology under the lubrication approach is used to
      formulate a set of three coupled nonlinear partial differential equations based
      on the Nusselt scales. This system, known as the energy-integral method in
      literature, simplifies the Navier-Stokes equation at the first order and analyzes
      the dynamics of a thin sheet of fluid flowing over a topography with sinusoidally
      varying longitudinal furrows. Limiting cases of the linear stability results are
      mathematically discussed and the complete linear system is numerically handled by
      means of finite differences to approximate the eigenfunctions and their
      derivatives in a periodic domain. In a geometry which resembles a vertical shift
      of a topography, with the amplitude being equal to the shift length, it is found
      that such a geometry stabilizes the flow compared to its counterpart with no
      shift, such that the wave characteristics get affected. To confirm the stability
      results, a numerical investigation is performed.

PMID- 22587183
TI  - How particle shape affects the flow through granular materials.
AB  - Flow through the pores of granular materials has many instances in practice.
      Therefore, it is interesting to realize how some parameters, such as the shape of
      the particles affect the passing flow. Following the recent mathematical theory
      proposed by the authors, this paper deals with the issue of how tortuosity and
      permeability are influenced by the particle shape. Comparison of the results with
      the experimental data reveals the competency of the theory in predicting the
      impact of particle geometry.

PMID- 22587184
TI  - Propagation limits and velocity of reaction-diffusion fronts in a system of
      discrete random sources.
AB  - The effect of spatially randomizing a system of pointlike sources on the
      propagation of reaction-diffusion fronts is investigated in multidimensions. The
      dynamics of the reactive front are modeled by superimposing the solutions for
      diffusion from a single point source. A nondimensional parameter is introduced to
      quantify the discreteness of the system, based on the characteristic reaction
      time of sources compared to the diffusion time between sources. The limits to
      propagation and the average velocity of propagation are expressed as
      probabilistic quantities to account for the influence of the randomly distributed
      sources. In random systems, two- and three-dimensional fronts are able to
      propagate beyond a limit previously found for systems with regularly distributed
      sources, while a propagation limit in one dimension that is independent of domain
      size cannot be defined. The dimensionality of the system is seen to have a strong
      influence on the front propagation velocity, with higher dimensional systems
      propagating faster than lower dimensional systems. In a three-dimensional system,
      both the limit to propagation and average front velocity revert to a solution
      that assumes a spatially continuous source function as the discreteness parameter
      is increased to the continuum limit. The results indicate that reactive systems
      are able to exploit local fluctuations in source concentration to extend
      propagation limits and increase the velocity in comparison to regularly spaced
      systems.

PMID- 22587185
TI  - Frequency spectrum of the noise emitted by two interacting cavitation bubbles in
      strong acoustic fields.
AB  - The dynamics and acoustic emission of two interacting cavitation bubbles exposed
      to strong acoustic fields with a frequency of 515 KHz are investigated
      numerically in this paper. After comparing the dynamics of a single bubble
      excited by the given pressure waves, bubbles with ambient radii of 2 and 5 MUm
      were chosen to be studied to discuss the influence of the mutual bubble-bubble
      interaction on the dynamic behaviors and acoustic emission of the bubbles. The
      results show that, aside from the external driving pressure waves, the
      interaction between the bubbles imposes an extra nonlinear effect on the
      oscillations of the bubbles and that the dynamics of the smaller bubble could be
      suppressed gradually with the enhancement of this mutual interaction by
      decreasing the distance between the bubbles. Moreover, the improvement in the
      oscillation nonlinearity of the bubbles due to the change in the ambient
      circumstance could readily be observed from the frequency spectra of the bubbles'
      acoustic emission, which interprets the change by exhibiting an appropriate
      development of the subharmonics, the ultraharmonics, and the broadband component.

PMID- 22587186
TI  - Depinning and creeplike motion of wetting fronts in weakly vibrated granular
      media.
AB  - We study the effect of weak vibrations on the imbibition of water in granular
      media. In our experiments, we have observed that as soon as the vibration is
      applied, an initially pinned wetting front advances in the direction of
      imbibition. We found that the front motion is governed by the avalanches of
      localized intermittent advances directed at 45 degrees  to the imbibition
      direction. When the rescaled gravitational acceleration of vertical vibrations is
      in the range of 0.81<=G<=0.95, we observed an almost steady motion of wetting
      front with a constant velocity v(cr)(G)?exp(-1/G) during more than 20 min,
      whereas at lower accelerations (0.5<=G<=0.8) the front velocity decreases in time
      as v?t(-delta). We suggest that the steady motion of an imbibition front in a
      weakly vibrated granular medium can be treated as a creep motion associated with
      nonthermal temporal fluctuations of packing density in a weakly vibrated granular
      medium.

PMID- 22587187
TI  - Water film motor driven by alternating electric fields: its dynamical
      characteristics.
AB  - The "liquid film motor," a novel device with important implications for basic
      research and technology, is analyzed. It works perfectly with both direct current
      (dc) and alternating current (ac) fields. We develop a mathematical model
      describing electrohydrodynamical (EHD) motions induced by ac fields, which are
      more complex and have wider technological applications than those produced by dc
      fields. The main characteristics of these motions, derived in our paper and in
      full agreement with the experimental ones, are as follows: (i) Rotation of the
      film requires that the frequencies of the ac fields are exactly the same and
      their magnitudes surpass a threshold, which depends on their phase difference.
      (ii) Vibrations may be induced by fields with different frequencies. (iii) The
      EHD motions strongly depend on the polarization induced by the external electric
      field. However, these motions are little affected by the liquid's electrical
      conductivity, viscosity, dielectric constant, and density. Our model also
      predicts several features, which have yet to be experimentally verified.

PMID- 22587188
TI  - Dynamics of saturated energy condensation in two-dimensional turbulence.
AB  - In two-dimensional forced Navier-Stokes turbulence, energy cascades to the
      largest scales in the system to form a pair of coherent vortices known as the
      Bose condensate. We show, both numerically and analytically, that the energy
      condensation saturates and the system reaches a statistically stationary state.
      The time scale of saturation is inversely proportional to the viscosity and the
      saturation energy level is determined by both the viscosity and the force. We
      further show that, without sufficient resolution to resolve the small-scale
      enstrophy spectrum, numerical simulations can give a spurious result for the
      saturation energy level. We also find that the movement of the condensate is
      similar to the motion of an inertial particle with an effective drag force.
      Furthermore, we show that the profile of the saturated coherent vortices can be
      described by a Gaussian core with exponential wings.

PMID- 22587189
TI  - Model for polygonal hydraulic jumps.
AB  - We propose a phenomenological model for the polygonal hydraulic jumps discovered
      by Ellegaard and co-workers [Nature (London) 392, 767 (1998); Nonlinearity 12, 1
      (1999); Physica B 228, 1 (1996)], based on the known flow structure for the type
      II hydraulic jumps with a "roller" (separation eddy) near the free surface in the
      jump region. The model consists of mass conservation and radial force balance
      between hydrostatic pressure and viscous stresses on the roller surface. In
      addition, we consider the azimuthal force balance, primarily between pressure and
      viscosity, but also including nonhydrostatic pressure contributions from surface
      tension in light of recent observations by Bush and co-workers [J. Fluid Mech.
      558, 33 (2006); Phys. Fluids 16, S4 (2004)]. The model can be analyzed by
      linearization around the circular state, resulting in a parameter relationship
      for nearly circular polygonal states. A truncated but fully nonlinear version of
      the model can be solved analytically. This simpler model gives rise to polygonal
      shapes that are very similar to those observed in experiments, even though
      surface tension is neglected, and the condition for the existence of a polygon
      with N corners depends only on a single dimensionless number phi. Finally, we
      include time-dependent terms in the model and study linear stability of the
      circular state. Instability occurs for sufficiently small Bond number and the
      most unstable wavelength is expected to be roughly proportional to the width of
      the roller as in the Rayleigh-Plateau instability.

PMID- 22587190
TI  - Dielectric function beyond the random-phase approximation: kinetic theory versus
      linear response theory.
AB  - Calculating the frequency-dependent dielectric function for strongly coupled
      plasmas, the relations within kinetic theory and linear response theory are
      derived and discussed in comparison. In this context, we give a proof that the
      Kohler variational principle can be extended to arbitrary frequencies. It is
      shown to be a special case of the Zubarev method for the construction of a
      nonequilibrium statistical operator from the principle of the extremum of entropy
      production. Within kinetic theory, the commonly used energy-dependent relaxation
      time approach is strictly valid only for the Lorentz plasma in the static case.
      It is compared with the result from linear response theory that includes electron
      electron interactions and applies for arbitrary frequencies, including
      bremsstrahlung emission. It is shown how a general approach to linear response
      encompasses the different approximations and opens options for systematic
      improvements.

PMID- 22587191
TI  - Harmonic analysis of irradiation asymmetry for cylindrical implosions driven by
      high-frequency rotating ion beams.
AB  - Cylindrical implosions driven by intense heavy ion beams should be instrumental
      in the near future for study of high-energy-density matter. By rotating the beam
      by means of a high-frequency wobbler, it should be possible to deposit energy in
      the outer layers of a cylinder, compressing the material deposited in its core.
      The beam's temporal profile should, however, generate an inevitable irradiation
      asymmetry likely to feed the Rayleigh-Taylor instability (RTI) during the
      implosion phase. In this paper, we compute the Fourier components of the target
      irradiation in order to make the connection with previous works on the RTI
      performed in this setting. Implementing one- and two-dimensional beam models, we
      find that these components can be expressed exactly in terms of the Fourier
      transform of the temporal beam profile. If T is the beam duration and Omega its
      rotation frequency, "magic products" OmegaT can be identified which cancel the
      first harmonic of the deposited density, resulting in an improved irradiation
      symmetry.

PMID- 22587192
TI  - Floating potential of large dust grains in a collisionless flowing plasma.
AB  - Dust immersed in plasma quickly charges to a potential where the ion and electron
      currents to its surface balance; this is the floating potential. In order to
      accurately determine dust behavior, the floating potential must be known. The
      charging of dust grains that are small with respect to electron Debye length
      (lambda(D)) may be adequately approximated using the orbital-motion-limited (OML)
      approach. A modified version of OML is presented for large dust grains in both
      stationary and flowing plasmas. This modified OML is compared with simulation and
      found to be in good agreement. The modified OML is applied to large grains
      charging under tokamak conditions and found to have an appreciable effect on the
      drag force.

PMID- 22587193
TI  - Effect of quantum correction on the acceleration and delayed heating of plasma
      blocks.
AB  - The interaction of laser pulses of picosecond duration and terawatt to petawatt
      power accelerated for the very fast undistorted plasma blocks for deuterium DD or
      deuterium tritium fast ignition is investigated. Based on the direct and instant
      conversion of laser energy into mechanical motion by nonlinear (ponderomotive)
      forces, any thermal pressure generation is delayed by the collision process.
      Following the studying of the classical collision frequency, it is found that the
      quantum modified collision at higher energies results in a correction by about
      15% reduction of the delay.

PMID- 22587194
TI  - Laser ion acceleration using a solid target coupled with a low-density layer.
AB  - We investigate by particle-in-cell simulations in two and three dimensions the
      laser-plasma interaction and the proton acceleration in multilayer targets where
      a low-density ("near-critical") layer of a few-micron thickness is added on the
      illuminated side of a thin, high-density layer. This target design can be
      obtained by depositing a "foam" layer on a thin metallic foil. The presence of
      the near-critical plasma strongly increases both the conversion efficiency and
      the energy of electrons and leads to enhanced acceleration of protons from a rear
      side layer via the target normal sheath acceleration mechanism. The electrons of
      the foam are strongly accelerated in the forward direction and propagate on the
      rear side of the target, building up a high electric field with a relatively flat
      longitudinal profile. In these conditions the maximum proton energy is up to
      three times higher than in the case of the bare solid target.

PMID- 22587195
TI  - Weak Alfven-wave turbulence revisited.
AB  - Weak Alfvenic turbulence in a periodic domain is considered as a mixed state of
      Alfven waves interacting with the two-dimensional (2D) condensate. Unlike in
      standard treatments, no spectral continuity between the two is assumed, and,
      indeed, none is found. If the 2D modes are not directly forced, k(-2) and k(-1)
      spectra are found for the Alfven waves and the 2D modes, respectively, with the
      latter less energetic than the former. The wave number at which their energies
      become comparable marks the transition to strong turbulence. For imbalanced
      energy injection, the spectra are similar, and the Elsasser ratio scales as the
      ratio of the energy fluxes in the counterpropagating Alfven waves. If the 2D
      modes are forced, a 2D inverse cascade dominates the dynamics at the largest
      scales, but at small enough scales, the same weak and then strong regimes as
      described above are achieved.

PMID- 22587196
TI  - Anisotropic scattering effects of a gyrotropic sphere characterized using the T
      matrix method.
AB  - Solutions for characterizing both electromagnetic wave propagation in, and
      scattering by, a gyrotropic sphere are obtained based on some recently published
      literature. Both gyrotropic permittivity and permeability tensors are considered
      herein, and both transmitted internal fields and scattered external fields are
      derived theoretically. Compared with problems of a uniaxial sphere, a
      gyroelectric sphere, and a gyromagnetic sphere, the scattering problem considered
      here is found to be astonishingly complicated but more generalized in formulation
      and solution procedure. Numerical validations are made by reducing our results to
      a gyromagnetic sphere and comparing them with the results obtained using the
      Fourier transform method, where excellent agreements are observed. Then, radar
      cross sections (RCSs) versus electric and magnetic gyrotropy ratios are computed,
      while hybrid effects due to both electric and magnetic gyrotropies are studied
      extensively, where some special cases of uniaxial spheres are demonstrated. It is
      shown that characteristics of gyrotropy parameters in Cartesian coordinates may
      lead to considerably large variations in RCS values, elucidating physical
      significance of gyrotropy and anisotropy ratios in scattering control. The
      generalized formulation of the problem is expected to have wide practical
      applications, while some features of this gyrotropic sphere may help other
      researchers or engineers to understand more physical insight. In addition, some
      critical mistakes made in literature were corrected.

PMID- 22587197
TI  - Highly nonlinear solitary wave propagation in Y-shaped granular crystals with
      variable branch angles.
AB  - We study the propagation of highly nonlinear waves in a branched (Y-shaped)
      granular crystal composed of chains of spherical particles of different
      materials, arranged at variable branch angles. We experimentally test the dynamic
      behavior of a solitary pulse, or of a train of solitary waves, crossing the Y
      junction interface, and splitting between the two branches. We describe the
      dependence of the split pulses' speed and amplitude on the branch angles.
      Analytic predictions based on the quasiparticle model and numerical simulations
      based on Hertzian interactions between the particles are found to be in excellent
      agreement with the experimental data.

PMID- 22587198
TI  - Generalized van der Waals Hamiltonian: periodic orbits and C1 nonintegrability.
AB  - The aim of this paper is to study the periodic orbits of the generalized van der
      Waals Hamiltonian system. The tool for studying such periodic orbits is the
      averaging theory. Moreover, for this Hamiltonian system we provide information on
      its C(1) nonintegrability, i.e., on the existence of a second first integral of
      class C(1).

PMID- 22587199
TI  - Phase extraction in disordered isospectral shapes.
AB  - The phase of the electronic wave function is not directly measurable but, quite
      remarkably, it becomes accessible in pairs of isospectral shapes, as recently
      proposed in the experiment by Moon et al. [Science 319, 782 (2008)]. The method
      is based on a special property, called transplantation, which relates the
      eigenfunctions of the isospectral pairs, and allows us to extract the phase
      distributions, if the amplitude distributions are known. We numerically simulate
      such a phase extraction procedure in the presence of disorder, which is
      introduced both as Anderson disorder and as roughness at edges. With disorder,
      the transplantation can no longer lead to a perfect fit of the wave functions,
      however we show that a phase can still be extracted-defined as the phase that
      minimizes the misfit. Interestingly, this extracted phase coincides with (or
      differs negligibly from) the phase of the disorder-free system, up to a certain
      disorder amplitude, and a misfit of the wave functions as high as ~5%, proving a
      robustness of the phase extraction method against disorder. However, if the
      disorder is increased further, the extracted phase shows a puzzle structure, no
      longer correlated with the phase of the disorder-free system. A discrete model is
      used, which is the natural approach for disorder analysis. We provide a proof
      that discretization preserves isospectrality and the transplantation can be
      adapted to the discrete systems.

PMID- 22587200
TI  - Soliton interactions and complexes for coupled nonlinear Schrodinger equations.
AB  - Under investigation in this paper are the coupled nonlinear Schrodinger (CNLS)
      equations, which can be used to govern the optical-soliton propagation and
      interaction in such optical media as the multimode fibers, fiber arrays, and
      birefringent fibers. By taking the 3-CNLS equations as an example for the N-CNLS
      ones (N>=3), we derive the analytic mixed-type two- and three-soliton solutions
      in more general forms than those obtained in the previous studies with the Hirota
      method and symbolic computation. With the choice of parameters for those soliton
      solutions, soliton interactions and complexes are investigated through the
      asymptotic and graphic analysis. Soliton interactions and complexes with the
      bound dark solitons in a mode or two modes are observed, including that (i) the
      two bright solitons display the breatherlike structures while the two dark ones
      stay parallel, (ii) the two bright and dark solitons all stay parallel, and (iii)
      the states of the bound solitons change from the breatherlike structures to the
      parallel one even with the distance between those solitons smaller than that
      before the interaction with the regular one soliton. Asymptotic analysis is also
      used to investigate the elastic and inelastic interactions between the bound
      solitons and the regular one soliton. Furthermore, some discussions are extended
      to the N-CNLS equations (N>3). Our results might be helpful in such applications
      as the soliton switch, optical computing, and soliton amplification in the
      nonlinear optics.

PMID- 22587201
TI  - Effective particles and classification of the dynamics of homogeneous granular
      chains with no precompression.
AB  - We develop a systematic methodology for classifying the periodic orbits of
      homogeneous ordered granular chains with no dissipation, under the assumption
      that all granules oscillate with the same frequency. The analysis is based on the
      idea of balancing linear momentum for sets of auxiliary models consisting of
      "effective particles." The auxiliary models may be defined for any given finite,
      ordered granular chain composed of n identical granules (beads) that interact
      with each other through strongly nonlinear Hertzian interaction law. In turn, the
      auxiliary models may be effectively used for theoretically predicting the total
      number of periodic orbits and the corresponding amplitude ratios of the granules.
      Good correspondence between the theoretical models and results of direct
      numerical simulations is reported. The results presented herein can be used to
      understand the complex intrinsic dynamics of ordered granular media, and to
      systematically study the generation of mode localization in these strongly
      nonlinear systems. The derived analytical models can be utilized to predict the
      response of the effective particles, and based on that, to predict primary pulse
      transmission in periodic layered media with granular interfaces. Moreover, our
      analysis can be extended to the general class of nonlinear chains of particles
      with smooth interacting potentials and possible separation between particles
      during the motion.

PMID- 22587202
TI  - Dynamics of analytical three-dimensional solutions in Bose-Einstein condensates
      with time-dependent gain and potential.
AB  - Using the F-expansion method we systematically present exact solutions of the
      three-dimensional nonlinear generalized Gross-Pitaevskii equation, with time
      varying gain or loss, in both attractive and expulsive harmonic confinement
      regimes. This approach allows us to obtain solitons for a large variety of
      solutions depending on the time-varying potential and the gain or loss profiles.
      The dynamics of these matter waves, including quasibreathing solitons, double
      quasibreathing solitons, and three-quasibreathing solitons, is discussed. The
      explicit functions that describe the evolution of the amplitude, width, and
      trajectory of the soliton's wave center are presented exactly. It is demonstrated
      that an arbitrary additional time-dependent gain function can be added to the
      model to control the amplitude and width of the soliton and the nonlinearity
      without affecting the motion of the solitons' wave center. Additionally, a number
      of exact traveling waves, including the Faraday pattern formation, have been
      found. The obtained results may raise the possibility of relative experiments and
      potential applications.

PMID- 22587203
TI  - Analysis of two-dimensional photonic band gaps of any rod shape and conductivity
      using a conical-integral-equation method.
AB  - The conical-boundary-integral-equation method has been proposed for calculation
      of the sensitive optical response of two-dimensional photonic band gaps (PBGs),
      including dielectric, absorbing, and high-conductive rods of various shapes
      working in any wavelength range. It is possible to determine the diffracted field
      by computing the scattering matrices separately for any grating boundary profile.
      The computation of the matrices is based on the solution of a 2*2 system of
      singular integral equations at each interface between two different materials.
      The advantage of our integral formulation is that the discretization of the
      integral equation system and the factorization of the discrete matrices, which
      takes the majority of the computing time, are carried out only once for a
      boundary. It turns out that a small number of collocation points per boundary
      combined with a high convergence rate can provide an adequate description of the
      dependence on diffracted energy of very different PBGs illuminated at arbitrary
      incident and polarization angles. The numerical results presented describe the
      significant impact of rod shape on diffraction in PBGs supporting polariton
      plasmon excitation, particularly in the vicinity of resonances and at high
      filling ratios. The diffracted energy response calculated vs the array cell
      geometry parameters was found to vary from a few up to a few hundred percent. The
      influence of other types of anomalies (i.e., waveguide anomalies, cavity modes,
      Fabry-Perot and Bragg resonances, Rayleigh orders, etc.), conductivity, and
      polarization states on the optical response is demonstrated.

PMID- 22587204
TI  - Parallel-pulling protocol for free-energy evaluation.
AB  - Jarzynski's equality (JE) allows us to compute free-energy differences from
      distributions of work. In molecular dynamics simulations, the traditional way of
      constructing work distributions is to perform as many pulling simulations as
      possible. But reliable work distributions are not always produced in a finite
      number of simulations. The computational cost of using JE is not less than other
      commonly used methods such as thermodynamic integration and umbrella sampling
      methods. Here we first show a different proof of JE based on the idea of stepwise
      pulling procedures that is efficient in computing free energies by using JE. The
      key point in our proof is that the processes of turning on or off a harmonic
      potential to perform work are described by double Heaviside functions of time. We
      then show that the distributions of work performed by the potential can be easily
      generated from the distributions of a reaction coordinate along a pathway. Based
      on the proof, we propose sequential and parallel stepwise pulling protocols for
      generating work distributions that require suitable relaxation time at each
      pulling step. The criterion for reliable work distributions is that there must be
      sufficient mutual overlaps between the adjacent distributions of the reaction
      coordinate along the pathway. We arrive at an alternative formula (besides JE) to
      compute free-energy differences from the averaged values of the reaction
      coordinate. The combination of JE and the alternative formula provides a viable
      way to determine the accuracy of computed free-energy differences. For the
      stretching of a deca-alanine molecule, our approach requires 21 parallel
      simulations and relaxation time as small as 0.4 ns for each simulation to
      estimate free-energy differences with an uncertainty of about 13%.

PMID- 22587205
TI  - Compact computations based on a stream-function-velocity formulation of two
      dimensional steady laminar natural convection in a square cavity.
AB  - A class of compact second-order finite difference algorithms is proposed for
      solving steady-state laminar natural convection in a square cavity using the
      stream-function-velocity (psi-u) form of Navier-Stokes equations. The stream
      function-velocity equation and the energy equation are all solved as a coupled
      system of equations for the four field variables consisting of stream function,
      two velocities, and temperature. Two strategies are considered for the
      discretizaton of the temperature equation, which are a second-order five-point
      compact scheme and a fourth-order nine-point compact scheme, respectively. The
      numerical capability of the presented algorithm is demonstrated by the
      application to natural convection in a square enclosure for a wide range of
      Rayleigh numbers (from 10(3) to 10(8)) and compared with some of the accurate
      results available in the literature. The presented schemes not only show second
      order accurate, but also prove effective. For larger Rayleigh numbers, the
      algorithm combining the second-order compact scheme for the stream-function
      velocity equation with the fourth-order compact scheme for the temperature
      equation performs more stably and effectively.

PMID- 22587206
TI  - Generalized Monte Carlo loop algorithm for two-dimensional frustrated Ising
      models.
AB  - We introduce a generalized loop move (GLM) update for Monte Carlo simulations of
      frustrated Ising models on two-dimensional lattices with bond-sharing plaquettes.
      The GLM updates are designed to enhance Monte Carlo sampling efficiency when the
      system's low-energy states consist of an extensive number of degenerate or near
      degenerate spin configurations, separated by large energy barriers to single spin
      flips. Through implementation on several frustrated Ising models, we demonstrate
      the effectiveness of the GLM updates in cases where both degenerate and near
      degenerate sets of configurations are favored at low temperatures. The GLM
      update's potential to be straightforwardly extended to different lattices and
      spin interactions allows it to be readily adopted on many other frustrated Ising
      models of physical relevance.

PMID- 22587207
TI  - Excitation gap from optimized correlation functions in quantum Monte Carlo
      simulations.
AB  - We give a prescription for finding optimized correlation functions for the
      extraction of the gap to the first excited state within quantum Monte Carlo
      simulations. We demonstrate that optimized correlation functions provide a more
      accurate reading of the gap when compared to other "nonoptimized" correlation
      functions and are generally characterized by considerably larger signal-to-noise
      ratios. We also analyze the cost of the procedure and show that it is not
      computationally demanding. We illustrate the effectiveness of the proposed
      procedure by analyzing several exemplary many-body systems of interacting spin
      1/2 particles.

PMID- 22587208
TI  - Finite-size scaling for quantum criticality using the finite-element method.
AB  - Finite size scaling for the Schrodinger equation is a systematic approach to
      calculate the quantum critical parameters for a given Hamiltonian. This approach
      has been shown to give very accurate results for critical parameters by using a
      systematic expansion with global basis-type functions. Recently, the finite
      element method was shown to be a powerful numerical method for ab initio
      electronic-structure calculations with a variable real-space resolution. In this
      work, we demonstrate how to obtain quantum critical parameters by combining the
      finite-element method (FEM) with finite size scaling (FSS) using different ab
      initio approximations and exact formulations. The critical parameters could be
      atomic nuclear charges, internuclear distances, electron density, disorder,
      lattice structure, and external fields for stability of atomic, molecular systems
      and quantum phase transitions of extended systems. To illustrate the
      effectiveness of this approach we provide detailed calculations of applying FEM
      to approximate solutions for the two-electron atom with varying nuclear charge;
      these include Hartree-Fock, local density approximation, and an "exact"
      formulation using FEM. We then use the FSS approach to determine its critical
      nuclear charge for stability; here, the size of the system is related to the
      number of elements used in the calculations. Results prove to be in good
      agreement with previous Slater-basis set calculations and demonstrate that it is
      possible to combine finite size scaling with the finite-element method by using
      ab initio calculations to obtain quantum critical parameters. The combined
      approach provides a promising first-principles approach to describe quantum phase
      transitions for materials and extended systems.

PMID- 22587209
TI  - Stabilized lattice Boltzmann-Enskog method for compressible flows and its
      application to one- and two-component fluids in nanochannels.
AB  - A numerically stable method to solve the discretized Boltzmann-Enskog equation
      describing the behavior of nonideal fluids under inhomogeneous conditions is
      presented. The algorithm employed uses a Lagrangian finite-difference scheme for
      the treatment of the convective term and a forcing term to account for the
      molecular repulsion together with a Bhatnagar-Gross-Krook relaxation term. In
      order to eliminate the spurious currents induced by the numerical discretization
      procedure, we use a trapezoidal rule for the time integration together with a
      version of the two-distribution method of He et al. [J. Comput. Phys. 152, 642
      (1999)]. Numerical tests show that, in the case of a one-component fluid in the
      presence of a spherical potential well, the proposed method reduces the numerical
      error by several orders of magnitude. We conduct another test by considering the
      flow of a two-component fluid in a channel with a bottleneck and provide
      information about the density and velocity field in this structured geometry.

PMID- 22587210
TI  - Analysis of intermittency in under-resolved smoothed-particle-hydrodynamics
      direct numerical simulations of forced compressible turbulence.
AB  - We perform three-dimensional under-resolved direct numerical simulations of
      forced compressible turbulence using the smoothed particle hydrodynamics (SPH)
      method and investigate the Lagrangian intermittency of the resulting hydrodynamic
      fields. The analysis presented here is motivated by the presence of typical
      stretched tails in the probability density function (PDF) of the particle
      accelerations previously observed in two-dimensional SPH simulations of uniform
      shear flow [Ellero et al., Phys. Rev. E 82, 046702 (2010)]. In order to produce a
      stationary isotropic compressible turbulent state, the real-space stochastic
      forcing method proposed by Kida and Orszag is applied, and the statistics of
      particle quantities are evaluated. We validate our scheme by checking the
      behavior of the energy spectrum in the supersonic case where the expected Burgers
      like scaling is obtained. By discretizing the continuum equations along fluid
      particle trajectories, the SPH method allows us to extract Lagrangian statistics
      in a straightforward fashion without the need for extra tracer particles. In
      particular, Lagrangian PDF of the density, particle accelerations as well as
      their Lagrangian structure functions and local scaling exponents are analyzed.
      The results for low-order statistics of Lagrangian intermittency in compressible
      turbulence demonstrate the implicit subparticle-scale modeling of the SPH
      discretization scheme.

PMID- 22587211
TI  - On-the-fly coarse-graining methodology for the simulation of chain formation of
      superparamagnetic colloids in strong magnetic fields.
AB  - The aim of this work is the description of the chain formation phenomena observed
      in colloidal suspensions of superparamagnetic nanoparticles under high magnetic
      fields. We introduce a methodology based on an on-the-fly coarse-grain (CG)
      model. Within this approach, the coarse-grain objects of the simulation and their
      dynamic behavior are not fixed a priori at the beginning of the simulation but
      rather redefined on the fly. The motion of the CG objects (single particles or
      aggregates) is described by an anisotropic diffusion model and the magnetic
      dipole-dipole interaction is replaced by an effective short-range interaction
      between CG objects. The methodology correctly reproduces previous results from
      detailed Langevin dynamics simulations of dispersions of superparamagnetic
      colloids under strong fields while requiring an amount of CPU time orders of
      magnitude smaller. This substantial improvement in the computational requirements
      allows the simulation of problems in which the relevant phenomena extend to time
      scales inaccessible with previous simulation techniques. A relevant example is
      the waiting time dependence of the relaxation time T(2) of water protons observed
      in magnetic resonance experiments containing dispersions of superparamagnetic
      colloids, which is correctly predicted by our simulations. Future applications
      may include other popular real-world applications of superparamagnetic colloids
      such as the magnetophoretic separation processes.

PMID- 22587212
TI  - Transition path sampling algorithm for discrete many-body systems.
AB  - We propose a Monte Carlo method for efficiently sampling trajectories with fixed
      initial and final conditions in a system with discrete degrees of freedom. The
      method can be applied to any stochastic process with local interactions,
      including systems that are out of equilibrium. We combine the proposed path
      sampling algorithm with thermodynamic integration to calculate transition rates.
      We demonstrate our method on the well-studied two-dimensional Ising model with
      periodic boundary conditions, and show agreement with other results for both
      large and small system sizes. The method scales well with the system size,
      allowing one to simulate systems with many degrees of freedom, and providing
      complementary information with respect to other algorithms.

PMID- 22587213
TI  - Percolation threshold determines the optimal population density for public
      cooperation.
AB  - While worldwide census data provide statistical evidence that firmly link the
      population density with several indicators of social welfare, the precise
      mechanisms underlying these observations are largely unknown. Here we study the
      impact of population density on the evolution of public cooperation in structured
      populations and find that the optimal density is uniquely related to the
      percolation threshold of the host graph irrespective of its topological details.
      We explain our observations by showing that spatial reciprocity peaks in the
      vicinity of the percolation threshold, when the emergence of a giant cooperative
      cluster is hindered neither by vacancy nor by invading defectors, thus
      discovering an intuitive yet universal law that links the population density with
      social prosperity.

PMID- 22587214
TI  - Traveling kinks in cubic nonlinear Ginzburg-Landau equations.
AB  - Nonlinear cubic Euler-Lagrange equations of motion in the traveling variable are
      usually derived from Ginzburg-Landau free energy functionals frequently
      encountered in several fields of physics. Many authors considered in the past
      damped versions of such equations, with the damping term added by hand simulating
      the friction due to the environment. It is known that even in this damped case
      kink solutions can exist. By means of a factorization method, we provide analytic
      formulas for several possible kink solutions of such equations of motion in the
      undriven and constant field driven cases, including the recently introduced
      Riccati parameter kinks, which were not considered previously in such a context.
      The latter parameter controls the delay of the switching stage of the kinks. The
      delay is caused by antikink components that are introduced in the structure of
      the solution through this parameter.

PMID- 22587215
TI  - Antiphase synchronization of phase-reduced oscillators using open-loop control.
AB  - In this report we present an elegant method to build and maintain an antiphase
      configuration of two nonlinear oscillators with different natural frequencies and
      dynamics described by the sinusoidal phase-reduced model. The antiphase
      synchronization is achieved using a common input that couples the oscillators and
      consists of a sequence of square pulses of appropriate amplitude and duration.
      This example provides a proof of principle that open-loop control can be used to
      create desired synchronization patterns for nonlinear oscillators, when feedback
      is expensive or impossible to obtain.

PMID- 22587216
TI  - Ion acoustic solitary waves in a plasma with nonthermal electrons featuring
      Tsallis distribution.
AB  - The model of Cairns et al. [Geophys. Res. Lett. 22, 2709 (1995)] is generalized.
      A physically meaningful nonextensive nonthermal velocity distribution is
      outlined. As the nonextensive character of the nonthermal electrons increases,
      the distribution shoulders may become less or more prominent and high-energy
      states are less or more probable than in the extensive nonthermal case. It is
      found that our plasma model supports the coexistence of smooth rarefactive and
      spiky compressive ion-acoustic solitary waves. The rarefactive solitons are more
      affected by nonextensivity than their compressive counterpart and a slight
      increase in the nonextensive parameter may destroy this dual nature.

PMID- 22587217
TI  - Defect modes in one-dimensional granular crystals.
AB  - We study the vibrational spectra of one-dimensional statically compressed
      granular crystals (arrays of elastic particles in contact) containing light-mass
      defects. We focus on the prototypical settings of one or two spherical defects
      (particles of smaller radii) interspersed in a chain of larger uniform spherical
      particles. We present a systematic measurement, using continuous noise, of the
      near-linear frequency spectrum within the spatial vicinity of the defect(s).
      Using this technique, we identify the frequencies of the localized defect modes
      as a function of the defect size and the position of the defects relative to each
      other. We also compare the experimentally determined frequencies with those
      obtained by numerical eigenanalysis and by analytical expressions based on few
      site considerations. These approximate analytical expressions, based on normal
      mode analysis, are found to be in excellent agreement with numerics for a wide
      range of mass ratios. We also observe that the experimentally measured
      frequencies of the localized defect modes are uniformly upshifted, compared to
      the numerically and theoretically predicted values.

PMID- 22587218
TI  - No stability switching at saddle-node bifurcations of solitary waves in
      generalized nonlinear Schrodinger equations.
AB  - Saddle-node bifurcations arise frequently in solitary waves of diverse physical
      systems. Previously it was believed that solitary waves always undergo stability
      switching at saddle-node bifurcations, just as in finite-dimensional dynamical
      systems. Here we show that this is not true. For a large class of generalized
      nonlinear Schrodinger equations with real or complex potentials, we prove that
      stability of solitary waves does not switch at saddle-node bifurcations. This
      analytical result is confirmed by numerical examples where both soliton branches
      are stable at saddle-node bifurcations.

PMID- 22587219
TI  - Exsanguination of a home hemodialysis patient as a result of misconnected blood
      lines during the wash back procedure: a case report.
AB  - BACKGROUND: Home hemodialysis is common in New Zealand and associated with lower
      cost, improved survival and better patient experience. We present the case of a
      fully trained home hemodialysis patient who exsanguinated at home as a result of
      an incorrect wash back procedure. CASE PRESENTATION: The case involves a 67 year
      old male with a history of well controlled hypertension and impaired glucose
      tolerance. He commenced on peritoneal dialysis in 2006 following the development
      of end stage kidney failure secondary to focal segmental glomerulosclerosis. He
      transferred to hemodialysis due to peritoneal membrane failure in 2010, and
      successfully trained for home hemodialysis over a 20 week period. Following one
      month of uncomplicated dialysis at home, he was found deceased on his machine at
      home in the midst of dialysis. His death occurred during the wash back procedure
      performed using the "open circuit" method, and resulted from misconnection of the
      saline bag to the venous end of the extracorporeal blood circuit instead of the
      arterial end. This led to approximately 2.3L of his blood being pumped into the
      saline bag resulting in hypovolaemic shock and death from exsanguination.
      CONCLUSIONS: Despite successful training, critical procedural errors can still be
      made by patients on home hemodialysis. In this case, the error involved
      misconnection of the saline bag for wash back. This case should prompt providers
      of home hemodialysis to review their training protocols and manuals.
      Manufacturers of dialysis machinery should be encouraged to design machines
      specifically for home hemodialysis, and consider distinguishing the arterial and
      venous ends of the extracorporeal blood circuit with colour coding or
      incompatible connectivity, to prevent occurrences such as these in the future.

PMID- 22587220
TI  - Employment of a noninvasive magnetic method for evaluation of gastrointestinal
      transit in rats.
AB  - AC Biosusceptometry (ACB) was previously employed towards recording
      gastrointestinal motility. Our data show a reliable and successful evaluation of
      gastrointestinal transit of liquid and solid meals in rats, considering the
      methods scarcity and number of experiments needed to endorsement of drugs and
      medicinal plants. ACB permits real time and simultaneous experiments using the
      same animal, preserving the physiological conditions employing both meals with
      simplicity and accuracy.

PMID- 22587221
TI  - A novel cost function to estimate parameters of oscillatory biochemical systems.
AB  - Oscillatory pathways are among the most important classes of biochemical systems
      with examples ranging from circadian rhythms and cell cycle maintenance.
      Mathematical modeling of these highly interconnected biochemical networks is
      needed to meet numerous objectives such as investigating, predicting and
      controlling the dynamics of these systems. Identifying the kinetic rate
      parameters is essential for fully modeling these and other biological processes.
      These kinetic parameters, however, are not usually available from measurements
      and most of them have to be estimated by parameter fitting techniques. One of the
      issues with estimating kinetic parameters in oscillatory systems is the
      irregularities in the least square (LS) cost function surface used to estimate
      these parameters, which is caused by the periodicity of the measurements. These
      irregularities result in numerous local minima, which limit the performance of
      even some of the most robust global optimization algorithms. We proposed a
      parameter estimation framework to address these issues that integrates temporal
      information with periodic information embedded in the measurements used to
      estimate these parameters. This periodic information is used to build a proposed
      cost function with better surface properties leading to fewer local minima and
      better performance of global optimization algorithms. We verified for three
      oscillatory biochemical systems that our proposed cost function results in an
      increased ability to estimate accurate kinetic parameters as compared to the
      traditional LS cost function. We combine this cost function with an improved
      noise removal approach that leverages periodic characteristics embedded in the
      measurements to effectively reduce noise. The results provide strong evidence on
      the efficacy of this noise removal approach over the previous commonly used
      wavelet hard-thresholding noise removal methods. This proposed optimization
      framework results in more accurate kinetic parameters that will eventually lead
      to biochemical models that are more precise, predictable, and controllable.

PMID- 22587222
TI  - Modulation of T-cell reactivity during equine pregnancy is antigen independent.
AB  - PROBLEM: Pregnant mares demonstrate a reduction in cytotoxic T lymphocyte (CTL)
      reactivity against cells from the breeding stallion. We investigated whether this
      effect is limited to activity against paternal major histocompatibility complex
      (MHC) antigens, and whether it occurs during MHC-compatible pregnancy. METHOD OF
      STUDY: Mares were mated to carry MHC-compatible or MHC-incompatible pregnancies.
      CTL activity of these mares when pregnant and non-pregnant was measured against
      cells from horses with MHC haplotypes unrelated to the mare or breeding stallion.
      RESULTS: While carrying MHC-incompatible pregnancies, mares demonstrated reduced
      CTL activity against lymphocytes from third-party horses in addition to those
      from the breeding stallion. This effect was also observed in mares carrying MHC
      compatible pregnancies. CONCLUSIONS: The decrease in maternal T-cell reactivity
      characteristic of normal equine pregnancy is not restricted to paternal
      alloantigen, and occurs during MHC-matched matings. This suggests that antigen
      independent mechanisms may be responsible for this reduction in cell-mediated
      immune activity.

PMID- 22587223
TI  - Stressful involvement in psychotherapeutic work: therapist, client and process
      correlates.
AB  - We examined potential predictors of therapists' "Stressful Involvement" (SI)
      among variables reflecting the psychotherapy process, therapist characteristics,
      patients' symptom severity or context variables (treatment setting). Ninety-eight
      sequences from individual psychodynamic treatments conducted by 26 therapists
      were studied. Data were analyzed using mixed regression models. Between-therapist
      and within-therapist variance accounted for most of the difference in SI. SI was
      strongly associated with negative feelings of the therapist about patient and
      therapy in the time between sessions. Therapists with more 'unassertive' and
      'vindictive' interpersonal styles were also more prone to experiencing SI. The
      strong association of SI with therapist rather than patient characteristics and
      process ratings indicates the importance of further study of the therapist as a
      person and participant in psychotherapy.

PMID- 22587224
TI  - Clinical correlates of chronic cerebrospinal venous insufficiency in multiple
      sclerosis.
AB  - BACKGROUND: Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular
      condition characterized by anomalies of the primary veins outside the skull that
      has been reported to be associated with MS. In the blinded Combined Transcranial
      (TCD) and Extracranial Venous Doppler Evaluation (CTEVD) study, we found that
      prevalence of CCSVI was significantly higher in multiple sclerosis (MS) vs.
      healthy controls (HC) (56.1% vs. 22.7%, p < 0.001).The objective was to evaluate
      the clinical correlates of venous anomalies indicative of CCSVI in patients with
      MS. METHODS: The original study enrolled 499 subjects; 163 HC, 289 MS, 21 CIS and
      26 subjects with other neurological disorders who underwent a clinical
      examination and a combined Doppler and TCD scan of the head and neck. This
      analysis was restricted to adult subjects with MS (RR-MS: n = 181, SP-MS: n = 80
      and PP-MS: n = 12). Disability status was evaluated by using the Kurtzke Expanded
      Disability Status Scale (EDSS) and MS severity scale (MSSS). RESULTS: Disability
      was not associated with the presence (>=2 venous hemodynamic criteria) or the
      severity of CCSVI, as measured with venous hemodynamic insufficiency severity
      score (VHISS). However, the severity of CCSVI was associated with the increased
      brainstem functional EDSS sub-score (p = 0.002). In logistic regression analysis,
      progressive MS (SP-MS or PP-MS) vs. non-progressive status (including RR-MS) was
      associated with CCSVI diagnosis (p = 0.004, OR = 2.34, CI = 1.3-4.2).
      CONCLUSIONS: The presence and severity of CCVSI in multiple sclerosis correlate
      with disease status but has no or very limited association with clinical
      disability.

PMID- 22587225
TI  - Mechanism of photogenerated reactive oxygen species and correlation with the
      antibacterial properties of engineered metal-oxide nanoparticles.
AB  - Oxidative stress induced by reactive oxygen species (ROS) is one of the most
      important antibacterial mechanisms of engineered nanoparticles (NPs). To
      elucidate the ROS generation mechanisms, we investigated the ROS production
      kinetics of seven selected metal-oxide NPs and their bulk counterparts under UV
      irradiation (365 nm). The results show that different metal oxides had distinct
      photogenerated ROS kinetics. Particularly, TiO(2) nanoparticles and ZnO
      nanoparticles generated three types of ROS (superoxide radical, hydroxyl radical,
      and singlet oxygen), whereas other metal oxides generated only one or two types
      or did not generate any type of ROS. Moreover, NPs yielded more ROS than their
      bulk counterparts likely due to larger surface areas of NPs providing more
      absorption sites for UV irradiation. The ROS generation mechanism was elucidated
      by comparing the electronic structures (i.e., band edge energy levels) of the
      metal oxides with the redox potentials of various ROS generation, which correctly
      interpreted the ROS generation of most metal oxides. To develop a quantitative
      relationship between oxidative stress and antibacterial activity of NPs, we
      examined the viability of E. coli cells in aqueous suspensions of NPs under UV
      irradiation, and a linear correlation was found between the average concentration
      of total ROS and the bacterial survival rates (R(2) = 0.84). Although some NPs
      (i.e., ZnO and CuO nanoparticles) released toxic ions that partially contributed
      to their antibacterial activity, this correlation quantitatively linked ROS
      production capability of NPs to their antibacterial activity as well as shed
      light on the applications of metal-oxide NPs as potential antibacterial agents.

PMID- 22587226
TI  - Bone mineral density directly correlates with duodenal Marsh stage in newly
      diagnosed adult celiac patients.
AB  - OBJECTIVES: To estimate the prevalence of low bone mineral density (BMD) in a
      prospective series of adult celiac patients and to identify nutritional and
      metabolic factors associated with osteoporosis and osteopenia. METHODS: Patients
      over 18 years of age who were consecutively and newly diagnosed with celiac
      disease (CD) were recruited. A bone density scan with dual-energy X-ray
      absorptiometry was carried out on the left hip and lumbar spine; nutritional
      parameters were analyzed and a hormone study conducted in order to exclude
      secondary low BMD. RESULTS: 40 patients (36 females/4 males) between the ages of
      18 and 68 (mean 44.25 years) were recruited. Overall, at the moment of diagnosis
      45% of patients exhibited low BMD at both demarcations. Risk of hip fracture was
      generally low, but ascended to mild in patients with villous atrophy (p = 0.011).
      Differences in major fracture risk were also observed depending on Marsh stage (p
      = 0.015). Significant differences were observed in nutritional status between
      patients with and without duodenal villous atrophy, with body mass index and
      blood levels of prealbumin, iron, vitamin D and folic acid significantly lower in
      Marsh III stage patients. No differences were found in blood hormone levels
      between Marsh stages or BMDs. The degree of bone mass loss in the lumbar spine
      directly correlated to Marsh stage. In the hip, a parallel association between
      BMD and Marsh stage was also observed, but did not reach statistical
      significance. CONCLUSION: Duodenal villous atrophy, through malabsorption, was
      the main determinant factor for low BMD in adult-onset CD patients.

PMID- 22587227
TI  - Covariance among premating, post-copulatory and viability fitness components in
      Drosophila melanogaster and their influence on paternity measurement.
AB  - In polyandrous mating systems, male fitness depends on success in premating, post
      copulatory and offspring viability episodes of selection. We tracked male success
      across all of these episodes simultaneously, using transgenic Drosophila
      melanogaster with ubiquitously expressed green fluorescent protein (i.e. GFP) in
      a series of competitive and noncompetitive matings. This approach permitted us to
      track paternity-specific viability over all life stages and to distinguish true
      competitive fertilization success from differential early offspring viability.
      Relationships between episodes of selection were generally not present when
      paternity was measured in eggs; however, positive correlations between sperm
      competitive success and offspring viability became significant when paternity was
      measured in adult offspring. Additionally, we found a significant male * female
      interaction on hatching success and a lack of repeatability of offspring
      viability across a focal male's matings, which may underlay the limited number of
      correlations found between episodes of selection.

PMID- 22587228
TI  - Neurovascular anatomical variations in the anterior palate observed on CBCT
      images.
AB  - OBJECTIVE: This study aimed to assess the presence of additional foramina and
      canals in the anterior palate region, through cone beam computed tomography
      (CBCT) images, describing their location, direction, and diameter. MATERIALS &
      METHODS: CBCT exams of 178 subjects displaying the anterior maxilla were included
      and the following parameters were registered: gender; age group; presence of
      additional foramina in the anterior palate (AFP) with at least 1 mm in diameter;
      location and diameter of AFP; and direction of bony canals associated with AFP.
      RESULTS: Twenty-eight patients (15.7%) presented AFP and in total 34 additional
      foramina were registered. No statistical differences between patients with or
      without AFP were found for gender or age. The average diameter of AFP was 1.4 mm
      (range from 1 to 1.9 mm). Their location was variable, with most of the cases
      occurring in the alveolar process near the incisors or canines (n = 27). In 18
      cases, AFP was associated with bony canals with upward or oblique direction
      toward the anterior nasal cavity floor. In 14 cases, the canal presented as a
      direct extension of the canalis sinuosus, in an upward direction laterally to the
      nasal cavity aperture. In two cases, the canal was observed adjacent to the
      incisive and joined the nasopalatine canal superiorly. DISCUSSION: CBCT images
      have a crucial role in the recognition of anatomical variations by allowing
      detailed tridimensional evaluations. Additional foramina and canals in the
      anterior region of the upper jaw are relatively frequent. Practitioners should be
      aware and trained to identify these variations. CONCLUSIONS: Over 15% of the
      population studied had additional foramina in the anterior palate, between 1 mm
      and 1.9 mm wide, with variable locations. In most cases the canals associated
      with these foramina either presented as a direct extension of the canalis
      sinuosus, or coursed towards the nasal cavity floor.

PMID- 22587229
TI  - Alterations of glutamate, glutamine, and related amino acids in the anterior eye
      secondary to ischaemia and reperfusion.
AB  - PURPOSE: To assess the amino acid levels of the ciliary epithelium, aqueous and
      lens under normal conditions and secondary to ischaemia and reperfusion. METHODS:
      We assessed the amino acids glutamate, glutamine, aspartate, alanine, gamma-amino
      butyric acid, glycine, arginine and taurine in albino Sprague-Dawley rats. Acute
      ischaemia was created in the eye and the different anterior eye components were
      assessed for amino acid levels. Quantitative immunocytochemistry was used to
      compare amino acid profiles within the ciliary processes immediately after
      ischaemia and after 4 days of reperfusion. Liquid chromatography was used to
      determine amino acid levels in the aqueous humour and quantitative
      immunocytochemistry to determine the location and alterations of amino acids in
      the lens 4 days after ischaemia/reperfusion. RESULTS: Elevated amino acid levels
      were evident in the ciliary epithelium immediately after ischaemia. After 4 days
      of reperfusion, decreased levels of glutamine, gamma-aminobutyric acid, glycine
      and arginine were evident in the ciliary epithelium, in particular the
      nonpigmented epithelial cells. The amino acid levels in the aqueous humour
      remained unchanged after ischaemia/reperfusion and thus showed considerable
      resilience to this kind of injury. However, significant reductions of glutamate,
      glutamine, alanine, glycine, arginine and taurine were observed in the lens 4
      days after ischaemia/reperfusion. CONCLUSIONS: We propose a model to explain the
      maintenance of amino acid homeostasis in the aqueous humour despite altered
      levels in both the ciliary processes and lens.

PMID- 22587230
TI  - Molecular dynamics unlocks atomic level self-assembly of the exopolysaccharide
      matrix of water-treatment granular biofilms.
AB  - Biofilm formation, in which bacteria are embedded within an extracellular matrix,
      is the default form of microbial life in most natural and engineered habitats. In
      this work, atomistic molecular dynamics simulations were employed to examine the
      self-assembly of the polysaccharide Granulan to provide insight into the
      molecular interactions that lead to biofilm formation. Granulan is a major gel
      forming matrix component of granular microbial biofilms found in used-water
      treatment systems. Molecular dynamics simulations showed that Granulan forms an
      antiparallel double helix stabilized by complementary hydrogen bonds between the
      beta-glucosamine of one strand and the N-acetyl-beta-galactosamine-2-acetoamido-2
      deoxy-alpha-galactopyranuronic pair of the other in both the presence and absence
      of Ca(2+). It is shown that Ca(2+) binds primarily to the carboxyl group of the
      terminal hexuronic acid of the sugar branch and that interactions between
      branches mediated by Ca(2+) suggest a possible mechanism for strengthening gels
      by facilitating interhelical bridging.

PMID- 22587231
TI  - The association between density of alcohol establishments and violent crime
      within urban neighborhoods.
AB  - BACKGROUND: Numerous studies have found that areas with higher alcohol
      establishment density are more likely to have higher violent crime rates, but
      many of these studies did not assess the differential effects of type of
      establishments or the effects on multiple categories of crime. In this study, we
      assess whether alcohol establishment density is associated with 4 categories of
      violent crime and whether the strength of the associations varies by type of
      violent crime and by on-premise establishments (e.g., bars, restaurants) versus
      off-premise establishments (e.g., liquor and convenience stores). METHODS: Data
      come from the city of Minneapolis, Minnesota in 2009 and were aggregated and
      analyzed at the neighborhood level. Across the 83 neighborhoods in Minneapolis,
      we examined 4 categories of violent crime: assault, rape, robbery, and total
      violent crime. We used a Bayesian hierarchical inference approach to model the
      data, accounting for spatial auto-correlation and controlling for relevant
      neighborhood demographics. Models were estimated for total alcohol establishment
      density as well as separately for on-premise establishments and off-premise
      establishments. RESULTS: Positive, statistically significant associations were
      observed for total alcohol establishment density and each of the violent crime
      outcomes. We estimate that a 3.9 to 4.3% increase across crime categories would
      result from a 20% increase in neighborhood establishment density. The
      associations between on-premise density and each of the individual violent crime
      outcomes were also all positive and significant and similar in strength as for
      total establishment density. The relationships between off-premise density and
      the crime outcomes were all positive but not significant for rape or total
      violent crime, and the strength of the associations was weaker than those for
      total and on-premise density. CONCLUSIONS: Results of this study, combined with
      earlier findings, provide more evidence that community leaders should be cautious
      about increasing the density of alcohol establishments within their
      neighborhoods.

PMID- 22587232
TI  - Injuries in preschool children: the hypothetical protector effect of minor
      injuries and risk factors for minor and medically attended injuries.
AB  - This study aimed to investigate the relationship between minor and medically
      attended injuries and to analyse the influence of child-related factors and
      family-related factors in injuries of preschool children. Individual interviews
      were conducted with 335 parents of 1- to 5-year-old children. Parents informed
      about the child and the family variables and reported the child's history of
      injuries in the last year. The frequencies of minor injuries and medically
      attended injuries were not correlated. The risk factors for both kinds of
      injuries include the number of siblings and the size of the family. Minor
      injuries were more frequent in older than in younger children. Medically attended
      injuries were more frequent in boys than in girls. The risk factors that
      influence minor and medically attended injuries are different, suggesting that
      the strategies to prevent and reduce injuries need to take that difference into
      consideration. 

PMID- 22587233
TI  - Quantum shock waves and domain walls in the real-time dynamics of a superfluid
      unitary Fermi gas.
AB  - We show that in the collision of two superfluid fermionic atomic clouds one
      observes the formation of quantum shock waves as discontinuities in the number
      density and collective flow velocity. Domain walls, which are topological
      excitations of the superfluid order parameter, are also generated and exhibit
      abrupt phase changes by pi and slower motion than the shock waves. The domain
      walls are distinct from the gray soliton train or number density ripples formed
      in the wake of the shock waves and observed in the collisions of superfluid
      bosonic atomic clouds. Domain walls with opposite phase jumps appear to collide
      elastically.

PMID- 22587234
TI  - Is a system's wave function in one-to-one correspondence with its elements of
      reality?
AB  - Although quantum mechanics is one of our most successful physical theories, there
      has been a long-standing debate about the interpretation of the wave function-
      the central object of the theory. Two prominent views are that (i) it corresponds
      to an element of reality, i.e., an objective attribute that exists before
      measurement, and (ii) it is a subjective state of knowledge about some underlying
      reality. A recent result [M. F. Pusey, J. Barrett, and T. Rudolph,
      arXiv:1111.3328] has placed the subjective interpretation into doubt, showing
      that it would contradict certain physically plausible assumptions, in particular,
      that multiple systems can be prepared such that their elements of reality are
      uncorrelated. Here we show, based only on the assumption that measurement
      settings can be chosen freely, that a system's wave function is in one-to-one
      correspondence with its elements of reality. This also eliminates the possibility
      that it can be interpreted subjectively.

PMID- 22587235
TI  - Observable measure of bipartite quantum correlations.
AB  - We introduce a measure Q of bipartite quantum correlations for arbitrary two
      qubit states, expressed as a state-independent function of the density matrix
      elements. The amount of quantum correlations can be quantified experimentally by
      measuring the expectation value of a small set of observables on up to four
      copies of the state, without the need for a full tomography. We extend the
      measure to 2*d systems, providing its explicit form in terms of observables and
      applying it to the relevant class of multiqubit states employed in the
      deterministic quantum computation with one quantum bit model. The number of
      required measurements to determine Q in our scheme does not increase with d. Our
      results provide an experimentally friendly framework to estimate quantitatively
      the degree of general quantum correlations in composite systems.

PMID- 22587236
TI  - Dynamical recurrence and the quantum control of coupled oscillators.
AB  - Controllability--the possibility of performing any target dynamics by applying a
      set of available operations--is a fundamental requirement for the practical use
      of any physical system. For finite-dimensional systems, such as spin systems,
      precise criteria to establish controllability, such as the so-called rank
      criterion, are well known. However, most physical systems require a description
      in terms of an infinite-dimensional Hilbert space whose controllability
      properties are poorly understood. Here, we investigate infinite-dimensional
      bosonic quantum systems--encompassing quantum light, ensembles of bosonic atoms,
      motional degrees of freedom of ions, and nanomechanical oscillators--governed by
      quadratic Hamiltonians (such that their evolution is analogous to coupled
      harmonic oscillators). After having highlighted the intimate connection between
      controllability and recurrence in the Hilbert space, we prove that, for coupled
      oscillators, a simple extra condition has to be fulfilled to extend the rank
      criterion to infinite-dimensional quadratic systems. Further, we present a useful
      application of our finding, by proving indirect controllability of a chain of
      harmonic oscillators.

PMID- 22587238
TI  - Nuclear correlations and the r process.
AB  - We show that long-range correlations for nuclear masses have a significant effect
      on the synthesis of heavy elements by the r process. As calculated by Delaroche
      et al. [Phys. Rev. C 81, 014303 (2010)], these correlations suppress magic number
      effects associated with minor shells. This impacts the calculated abundances
      before the third r-process peak (at mass number A~195), where the abundances are
      low and form a trough. This trough and the position of the third abundance peak
      are strongly affected by the masses of nuclei in the transition region between
      deformed and spherical. Based on different astrophysical environments, our
      results demonstrate that a microscopic theory of nuclear masses including
      correlations naturally smoothens the separation energies, thus reducing the
      trough and improving the agreement with observed solar system abundances.

PMID- 22587237
TI  - Near-equilibrium measurements of nonequilibrium free energy.
AB  - A central endeavor of thermodynamics is the measurement of free energy changes.
      Regrettably, although we can measure the free energy of a system in thermodynamic
      equilibrium, typically all we can say about the free energy of a nonequilibrium
      ensemble is that it is larger than that of the same system at equilibrium.
      Herein, we derive a formally exact expression for the probability distribution of
      a driven system, which involves path ensemble averages of the work over
      trajectories of the time-reversed system. From this we find a simple near
      equilibrium approximation for the free energy in terms of an excess mean time
      reversed work, which can be experimentally measured on real systems. With
      analysis and computer simulation, we demonstrate the accuracy of our
      approximations for several simple models.

PMID- 22587239
TI  - Rapidity renormalization group.
AB  - We introduce a systematic approach for the resummation of perturbative series
      which involves large logarithms not only due to large invariant mass ratios but
      large rapidities as well. A series of this form can appear in a variety of gauge
      theory observables. The formalism is utilized to calculate the jet broadening
      event shape in a systematic fashion to next-to-leading logarithmic order. An
      operator definition of the factorized cross section as well as a closed form of
      the next-to-leading-log cross section are presented. The result agrees with the
      data to within errors.

PMID- 22587240
TI  - Gauge coupling beta functions in the standard model to three loops.
AB  - In this Letter, we compute the three-loop corrections to the beta functions of
      the three gauge couplings in the standard model of particle physics using the
      minimal subtraction scheme and taking into account Yukawa and Higgs self
      couplings.

PMID- 22587241
TI  - Observation of B(s)(0) -> J/psif(2)'(1525) in J/psiK+ K- final states.
AB  - The decay B(s)(0) -> J/psiK+ K- is investigated using 0.16  fb(-1) of data
      collected with the LHCb detector using 7 TeV pp collisions. Although the J/psiphi
      channel is well known, final states at higher K+ K- masses have not previously
      been studied. In the K+ K- mass spectrum we observe a significant signal in the
      f(2)'(1525) region as well as a nonresonant component. After subtracting the
      nonresonant component, we find B(B(s)(0) -> J/psif(2)'(1525))/B(B(s)(0) ->
      J/psiphi) = (26.4 +/- 2.7 +/- 2.4)%.

PMID- 22587247
TI  - Direct measurement of the proton magnetic moment.
AB  - The proton magnetic moment in nuclear magnetons is measured to be MU(p)/MU(N) =
      g/2 = 2.792 846 +/- 0.000 007, a 2.5 parts per million uncertainty. The direct
      determination, using a single proton in a Penning trap, demonstrates the first
      method that should work as well with an antiproton (p) as with a proton (p). This
      opens the way to measuring the p magnetic moment (whose uncertainty has
      essentially not been reduced for 20 years) at least 10(3) times more precisely.

PMID- 22587246
TI  - Meson-exchange currents and quasielastic antineutrino cross sections in the
      superscaling approximation.
AB  - We evaluate quasielastic double-differential antineutrino cross sections obtained
      in a phenomenological model based on the superscaling behavior of electron
      scattering data and estimate the contribution of the vector meson-exchange
      currents in the two-particle-two-hole sector. We show that the impact of meson
      exchange currents for charge-changing antineutrino reactions is much larger than
      in the neutrino case.

PMID- 22587244
TI  - Measurement of the W boson mass with the D0 detector.
AB  - We present a measurement of the W boson mass using data corresponding to 4.3  fb(
      1) of integrated luminosity collected with the D0 detector during Run II at the
      Fermilab Tevatron pp collider. With a sample of 1,677,394 W -> enu candidate
      events, we measure M(W) = 80.367 +/- 0.026  GeV. This result is combined with an
      earlier D0 result determined using an independent Run II data sample,
      corresponding to 1  fb(-1) of integrated luminosity, to yield M(W) = 80.375 +/-
      0.023  GeV.

PMID- 22587248
TI  - High-accuracy measurement of atomic polarizability in an optical lattice clock.
AB  - Presently, the Stark effect contributes the largest source of uncertainty in a
      ytterbium optical atomic clock through blackbody radiation. By employing an
      ultracold, trapped atomic ensemble and high stability optical clock, we
      characterize the quadratic Stark effect with unprecedented precision. We report
      the ytterbium optical clock's sensitivity to electric fields (such as blackbody
      radiation) as the differential static polarizability of the ground and excited
      clock levels alpha(clock) = 36.2612(7)  kHz (kV/cm)(-2). The clock's uncertainty
      due to room temperature blackbody radiation is reduced by an order of magnitude
      to 3*10(-17).

PMID- 22587251
TI  - Two-photon path-entangled states in multimode waveguides.
AB  - We experimentally show that two-photon path-entangled states can be coherently
      manipulated by multimode interference in multimode waveguides. By measuring the
      output two-photon spatial correlation function versus the phase of the input
      state, we show that multimode waveguides perform as nearly ideal multiport beam
      splitters at the quantum level, creating a large variety of entangled and
      separable multipath two-photon states.

PMID- 22587249
TI  - Experimental verification of the chemical sensitivity of two-site double core
      hole states formed by an x-ray free-electron laser.
AB  - We have performed x-ray two-photon photoelectron spectroscopy using the Linac
      Coherent Light Source x-ray free-electron laser in order to study double core
      hole (DCH) states of CO2, N2O, and N2. The experiment verifies the theory behind
      the chemical sensitivity of two-site DCH states by comparing a set of small
      molecules with respect to the energy shift of the two-site DCH state and by
      extracting the relevant parameters from this shift.

PMID- 22587252
TI  - Using interference for high fidelity quantum state transfer in optomechanics.
AB  - We revisit the problem of using a mechanical resonator to perform the transfer of
      a quantum state between two electromagnetic cavities (e.g., optical and
      microwave). We show that this system possesses an effective mechanically dark
      mode which is immune to mechanical dissipation; utilizing this feature allows
      highly efficient transfer of intracavity states, as well as of itinerant photon
      states. We provide simple analytic expressions for the fidelity for transferring
      both gaussian and non-gaussian states.

PMID- 22587250
TI  - Pulsed laser cooling for cavity optomechanical resonators.
AB  - A pulsed cooling scheme for optomechanical systems is presented that is capable
      of cooling at much faster rates, shorter overall cooling times, and for a wider
      set of experimental scenarios than is possible by conventional methods. The
      proposed scheme can be implemented for both strongly and weakly coupled
      optomechanical systems in both weakly and highly dissipative cavities. We study
      analytically its underlying working mechanism, which is based on interferometric
      control of optomechanical interactions, and we demonstrate its efficiency with
      pulse sequences that are obtained by using methods from optimal control. The
      short time in which our scheme approaches the optomechanical ground state allows
      for a significant relaxation of current experimental constraints. Finally, the
      framework presented here can be used to create a rich variety of optomechanical
      interactions and hence offers a novel, readily available toolbox for fast
      optomechanical quantum control.

PMID- 22587253
TI  - Adiabatic state conversion and pulse transmission in optomechanical systems.
AB  - Optomechanical systems with strong coupling can be a powerful medium for quantum
      state engineering of the cavity modes. Here, we show that quantum state
      conversion between cavity modes of distinctively different wavelengths can be
      realized with high fidelity by adiabatically varying the effective optomechanical
      couplings. The conversion fidelity for gaussian states is derived by solving the
      Langevin equation in the adiabatic limit. Meanwhile, we also show that traveling
      photon pulses can be transmitted between different input and output channels with
      high fidelity and the output pulse can be engineered via the optomechanical
      couplings.

PMID- 22587242
TI  - Measurements of the angular distributions of muons from Upsilon decays in pp
      collisions at sqrt[s] = 1.96  TeV.
AB  - The angular distributions of muons from Upsilon(1S,2S,3S) -> MU+ MU- decays are
      measured using data from pp collisions at sqrt[s] = 1.96  TeV corresponding to an
      integrated luminosity of 6.7  fb(-1) and collected with the CDF II detector at
      the Fermilab Tevatron. This analysis is the first to report the full angular
      distributions as functions of transverse momentum p(T) for Upsilon mesons in both
      the Collins-Soper and s-channel helicity frames. This is also the first
      measurement of the spin alignment of Upsilon(3S) mesons. Within the kinematic
      range of Upsilon rapidity |y|<0.6 and p(T) up to 40  GeV/c, the angular
      distributions are found to be nearly isotropic.

PMID- 22587243
TI  - Precise measurement of the W-boson mass with the CDF II detector.
AB  - We have measured the W-boson mass M(W) using data corresponding to 2.2  fb(-1) of
      integrated luminosity collected in pp collisions at sqrt[s] = 1.96  TeV with the
      CDF II detector at the Fermilab Tevatron collider. Samples consisting of 470,126
      W -> enu candidates and 624,708 W -> MUnu candidates yield the measurement M(W) =
      80,387 +/- 12(stat.) +/- 15(syst.) = 80,387 +/- 19  MeV/c2. This is the most
      precise measurement of the W-boson mass to date and significantly exceeds the
      precision of all previous measurements combined.

PMID- 22587254
TI  - Monolithic source of photon pairs.
AB  - The creation of monolithically integratable sources of single and entangled
      photons is a top research priority with formidable challenges: The production,
      manipulation, and measurement of the photons should all occur in the same
      material platform, thereby fostering stability and scalability. Here we
      demonstrate efficient photon pair production in a semiconductor platform, gallium
      arsenide. Our results show type-I spontaneous parametric down-conversion of laser
      light from a 2.2 mm long Bragg-reflection waveguide, and we estimate its internal
      pair production efficiency to be 2.0*10(-8) (pairs/pump photon). This is the
      first time that significant pair production has been demonstrated in a structure
      that can be electrically self-pumped and which can form the basis for passive
      optical circuitry, bringing us markedly closer to complete integration of quantum
      optical technologies.

PMID- 22587255
TI  - Photonic Aharonov-Bohm effect based on dynamic modulation.
AB  - We show that when the refractive index of a photonic system is harmonically
      modulated, the phase of the modulation introduces an effective gauge potential
      for photons. This effective gauge potential can be used to create a photonic
      Aharonov-Bohm effect. We show that the photonic Aharonov-Bohm effect provides the
      optimal mechanism for achieving complete on-chip nonmagnetic optical isolation.

PMID- 22587256
TI  - Geometry of inertial manifolds probed via a Lyapunov projection method.
AB  - A method for determining the dimension and state space geometry of inertial
      manifolds of dissipative extended dynamical systems is presented. It works by
      projecting vector differences between reference states and recurrent states onto
      local linear subspaces spanned by the Lyapunov vectors. A sharp characteristic
      transition of the projection error occurs as soon as the number of basis vectors
      is increased beyond the inertial manifold dimension. Since the method can be
      applied using standard orthogonal Lyapunov vectors, it provides a possible way to
      also determine experimentally inertial manifolds and their geometric
      characteristics.

PMID- 22587257
TI  - Spider silk violin strings with a unique packing structure generate a soft and
      profound timbre.
AB  - We overcome the difficulties in pulling long draglines from spiders, twist
      bundles of dragline filaments, and succeed in preparing violin strings. The
      twisting is found to change the cross section shapes of filaments from circular
      to polygonal and to optimize the packing structure with no openings among
      filaments providing mechanically strong and elastic strings. The spider string
      signal peaks of overtones for the violin are relatively large at high
      frequencies, generating a soft and profound timbre. Such a preferable timbre is
      considered to be due to the unique polygonal packing structure which provides
      valuable knowledge for developing new types of materials.

PMID- 22587258
TI  - Ejection of uniform micrometer-sized droplets from Faraday waves on a millimeter
      sized water drop.
AB  - This Letter reports the first observation and theoretical analysis of a new
      phenomenon: one large spherical water drop ejecting simultaneously a very large
      number of monodisperse microdroplets. An ultrasonic nozzle with multiple-Fourier
      horns in resonance enables controlled excitation of megahertz Faraday waves on
      the free water surface. The temporal instability of such waves leads to the
      ejection of 3.5-4.4  MUm monodisperse droplets at a high rate (>4.0*10(7) 
      droplets/sec). This is in stark contrast to the Rayleigh-Plateau instability,
      which ejects one droplet at a time.

PMID- 22587259
TI  - Observation of a free-Shercliff-layer instability in cylindrical geometry.
AB  - We report on observations of a free-Shercliff-layer instability in a Taylor
      Couette experiment using a liquid metal over a wide range of Reynolds numbers,
      Re~10(3)-10(6). The free Shercliff layer is formed by imposing a sufficiently
      strong axial magnetic field across a pair of differentially rotating axial end
      cap rings. This layer is destabilized by a hydrodynamic Kelvin-Helmholtz-type
      instability, characterized by velocity fluctuations in the r-theta plane. The
      instability appears with an Elsasser number above unity, and saturates with an
      azimuthal mode number m which increases with the Elsasser number. Measurements of
      the structure agree well with 2D global linear mode analyses and 3D global
      nonlinear simulations. These observations have implications for a range of
      rotating MHD systems in which similar shear layers may be produced.

PMID- 22587260
TI  - Fusion using fast heating of a compactly imploded CD core.
AB  - A compact fast core heating experiment is described. A 4-J 0.4-ns output of a
      laser-diode-pumped high-repetition laser HAMA is divided into four beams, two of
      which counterilluminate double-deuterated polystyrene foils separated by 100  MUm
      for implosion. The remaining two beams, compressed to 110 fs for fast heating,
      illuminate the same paths. Hot electrons produced by the heating pulses heat the
      imploded core, emitting x-ray radiations >20  eV and yielding some 10(3) thermal
      neutrons.

PMID- 22587261
TI  - Role of zonal flow predator-prey oscillations in triggering the transition to H
      mode confinement.
AB  - Direct evidence of zonal flow (ZF) predator-prey oscillations and the synergistic
      roles of ZF- and equilibrium E*B flow shear in triggering the low- to high
      confinement (L- to H-mode) transition in the DIII-D tokamak is presented.
      Periodic turbulence suppression is first observed in a narrow layer at and just
      inside the separatrix when the shearing rate transiently exceeds the turbulence
      decorrelation rate. The final transition to H mode with sustained turbulence and
      transport reduction is controlled by equilibrium E*B shear due to the increasing
      ion pressure gradient.

PMID- 22587262
TI  - Observation of magnetically induced transparency in a classical magnetized
      plasma.
AB  - We report the first demonstration of magnetically induced transmission in an
      opaque magnetized plasma. Magnetically induced transmission in a plasma is a
      classical analog to the electromagnetically induced transparency in atomic
      systems. The transmission of radiation through an axially magnetized plasma is
      obtained by applying an additional one dimensional transverse spatial periodic
      magnetic field. The transverse-periodic magnetic field uncouples the right-hand
      electromagnetic wave from interacting with plasma electrons, rendering the plasma
      band-stop transparent. This provides means to control the extent of absorption of
      electromagnetic radiation in magnetized plasma.

PMID- 22587263
TI  - Bosonic superfluid-insulator transition in continuous space.
AB  - We investigate the zero-temperature phase diagram of interacting Bose gases in
      the presence of a simple cubic optical lattice, going beyond the regime where the
      mapping to the single-band Bose-Hubbard model is reliable. Our computational
      approach is a new hybrid quantum Monte Carlo method which combines algorithms
      used to simulate homogeneous quantum fluids in continuous space with those used
      for discrete lattice models of strongly correlated systems. We determine the
      critical interaction strength and optical lattice intensity where the superfluid
      to-insulator transition takes place, considering also the regime of shallow
      optical lattices and strong interatomic interactions. The implications of our
      findings for the supersolid state of matter are discussed.

PMID- 22587264
TI  - Traces of vortices in superfluid helium droplets.
AB  - We report on the observation of vortices in superfluid 4He droplets produced in
      the expansion of liquid He. The vortices were traced by introducing Ag atoms,
      which clustered along the vortex lines, into the droplets. The Ag clusters were
      subsequently surface-deposited and imaged via electron microscopy. The prevalence
      of elongated track-shaped deposits shows that vortices are present in droplets
      larger than about 300 nm and that their lifetime exceeds a few milliseconds. We
      discuss the possible formation mechanisms and the stability of the vortices.

PMID- 22587265
TI  - Silicene: compelling experimental evidence for graphenelike two-dimensional
      silicon.
AB  - Because of its unique physical properties, graphene, a 2D honeycomb arrangement
      of carbon atoms, has attracted tremendous attention. Silicene, the graphene
      equivalent for silicon, could follow this trend, opening new perspectives for
      applications, especially due to its compatibility with Si-based electronics.
      Silicene has been theoretically predicted as a buckled honeycomb arrangement of
      Si atoms and having an electronic dispersion resembling that of relativistic
      Dirac fermions. Here we provide compelling evidence, from both structural and
      electronic properties, for the synthesis of epitaxial silicene sheets on a silver
      (111) substrate, through the combination of scanning tunneling microscopy and
      angular-resolved photoemission spectroscopy in conjunction with calculations
      based on density functional theory.

PMID- 22587267
TI  - Nanotransformation and current fluctuations in exciton condensate junctions.
AB  - We analyze the nonlinear transport properties of a bilayer exciton condensate
      that is contacted by four metallic leads by calculating the full counting
      statistics of electron transport for arbitrary system parameters. Despite its
      formal similarity to a superconductor the transport properties of the exciton
      condensate turn out to be completely different. We recover the generic features
      of exciton condensates such as counterpropagating currents driven by excitonic
      Andreev reflections and make predictions for nonlinear transconductance between
      the layers as well as for the current (cross)correlations and generalized Johnson
      Nyquist relationships. Finally, we explore the possibility of connecting another
      mesoscopic system (in our case a quantum point contact) to the bottom layer of
      the exciton condensate and show how the excitonic Andreev reflections can be used
      for transforming voltage at the nanoscale.

PMID- 22587266
TI  - Reentrant mechanism for associative desorption: H2/Pt(110)-(1*2).
AB  - Calculations of the desorption of hydrogen from Pt(110)-(1*2), a surface used to
      model nanoparticle edge sites, show the activation energy varying strongly with
      hydrogen coverage, from 0.8 to 0.3 eV. The predicted temperature programed
      desorption spectra agree well with experiments, but the formation of the hydrogen
      molecules occurs only at two types of sites on the surface even though three
      peaks are observed. The lowest and highest temperature peaks result from
      desorption from the same strong binding sites at the ridge, while desorption from
      the weakest binding trough sites is insignificant.

PMID- 22587268
TI  - Inelastic electron backscattering in a generic helical edge channel.
AB  - We evaluate the low-temperature conductance of a weakly interacting one
      dimensional helical liquid without axial spin symmetry. The lack of that symmetry
      allows for inelastic backscattering of a single electron, accompanied by forward
      scattering of another. This joint effect of weak interactions and potential
      scattering off impurities results in a temperature-dependent deviation from the
      quantized conductance, deltaG ? T4. In addition, deltaG is sensitive to the
      position of the Fermi level. We determine numerically the parameters entering our
      generic model for the Bernevig-Hughes-Zhang Hamiltonian of a HgTe/CdTe quantum
      well in the presence of Rashba spin-orbit coupling.

PMID- 22587269
TI  - Shallow versus deep nature of Mg acceptors in nitride semiconductors.
AB  - We investigate the properties of Mg acceptors in nitride semiconductors with
      hybrid functional calculations. We find that although the thermodynamic
      transition level is relatively close to the valence band in GaN (260 meV), Mg(Ga)
      exhibits key features of a deep acceptor: the hole is localized on a N atom
      neighboring the Mg impurity, inducing a large local lattice distortion and giving
      rise to broad blue luminescence. We show that the ultraviolet photoluminescence
      peak attributed to Mg acceptors in GaN is likely related to Mg-H complexes,
      explaining the results of photoluminescence and electron paramagnetic resonance
      experiments. Predictions for Mg acceptors in AlN and InN are also presented.

PMID- 22587270
TI  - Topological Hall effect in pyrochlore lattice with varying density of spin
      chirality.
AB  - The three-site spin correlation, S(i).(S(j)*S(k)) on the neighboring triangular
      sites i, j and k, termed scalar spin chirality, can endow the conduction electron
      with a quantum Berry phase and resultant transverse (Hall) transport. The
      paramagnetic barely metallic state was prepared in hole-doped Y2Mo2O7 with
      pyrochlore lattice using a high-pressure synthesis method, which is further
      endowed with the spin chirality by partially replacing Y site with Tb (content
      x). The local spin chirality formed by the adjacent three Tb Ising moments on the
      pyrochlore lattice can couple to the conduction electrons to give rise to the
      topological Hall effect whose magnitude increases in proportion to x3 or the
      density of the Tb-moment triangular clusters.

PMID- 22587271
TI  - Suppression of inelastic electron-electron scattering in anderson insulators.
AB  - We report on measurements of absorption from applied ac fields in Anderson
      localized indium-oxide films. The absorption shows a roll-off at a frequency that
      is much smaller than the electron-electron scattering rate measured at the same
      temperature in diffusive samples of this material. These results are interpreted
      as evidence for discreteness of the energy spectrum.

PMID- 22587272
TI  - Optical spin injection and spin lifetime in Ge heterostructures.
AB  - We demonstrate optical orientation in Ge/SiGe quantum wells and study their spin
      properties. The ultrafast electron transfer from the center of the Brillouin zone
      to its edge allows us to achieve high spin polarizations and to resolve the spin
      dynamics of holes and electrons. The circular polarization degree of the direct
      gap photoluminescence exceeds the theoretical bulk limit, yielding ~37% and ~85%
      for transitions with heavy and light holes states, respectively. The spin
      lifetime of holes at the top of the valence band is estimated to be ~0.5  ps and
      it is governed by transitions between light and heavy hole states. Electrons at
      the bottom of the conduction band, on the other hand, have a spin lifetime that
      exceeds 5 ns below 150 K. Theoretical analysis of the spin relaxation indicates
      that phonon-induced intervalley scattering dictates the spin lifetime of
      electrons.

PMID- 22587273
TI  - Structure-dependent Fano resonances in the infrared spectra of phonons in few
      layer graphene.
AB  - The in-plane optical phonons around 200 meV in few-layer graphene are
      investigated utilizing infrared absorption spectroscopy. The phonon spectra
      exhibit unusual asymmetric features characteristic of Fano resonances, which
      depend critically on the layer thickness and stacking order of the sample. The
      phonon intensities in samples with rhombohedral (ABC) stacking are significantly
      higher than those with Bernal (AB) stacking. These observations reflect the
      strong coupling between phonons and interband electronic transitions in these
      systems and the distinctive variation in the joint density of electronic states
      in samples of differing thickness and stacking order.

PMID- 22587274
TI  - Designing electrical contacts to MoS2 monolayers: a computational study.
AB  - Studying the reason why single-layer molybdenum disulfide (MoS2) appears to fall
      short of its promising potential in flexible nanoelectronics, we find that the
      nature of contacts plays a more important role than the semiconductor itself. In
      order to understand the nature of MoS2/metal contacts, we perform ab initio
      density functional theory calculations for the geometry, bonding, and electronic
      structure of the contact region. We find that the most common contact metal (Au)
      is rather inefficient for electron injection into single-layer MoS2 and propose
      Ti as a representative example of suitable alternative electrode materials.

PMID- 22587275
TI  - Charge-transfer-induced cesium superlattices on graphene.
AB  - We investigate cesium (Cs) adsorption on graphene formed on a 6H-SiC(0001)
      substrate by a combined scanning tunneling microscopy and density functional
      theory study. Individual Cs atoms adsorb preferentially at the rim region of the
      well-defined 6*6 substrate superstructure and on multilayer graphene. By finely
      controlling the graphene thickness and Cs coverages (1/3  ML and 1 ML), we here
      demonstrate two intriguing and well-ordered Cs superlattices on bilayer and
      multilayer graphene (<6   layers). Statistical analysis of the Cs-Cs interatomic
      distance reveals a hitherto unobserved Cs-Cs long-range electrostatic potential
      caused by charge transfer from Cs to graphene, which couples with the
      inhomogeneous substrate potential to stabilize the observed Cs superlattices. The
      present study provides a new avenue to fabricate atomic and molecular
      superlattices for applications in high-density recording and data storage.

PMID- 22587276
TI  - Intrinsic Hall effect in a multiband chiral superconductor in the absence of an
      external magnetic field.
AB  - We identify an intrinsic Hall effect in multiband chiral superconductors in the
      absence of a magnetic field (i.e., an anomalous Hall effect). This effect arises
      from interband transitions involving time-reversal symmetry-breaking chiral
      Cooper pairs. We discuss the implications of this effect for the putative chiral
      p-wave superconductor, Sr2RuO4, and show that it can contribute significantly to
      Kerr rotation experiments. Since the magnitude of the effect depends on the
      structure of the order parameter across the bands, this result may be used to
      distinguish between different models proposed for the superconducting state of
      Sr2RuO4.

PMID- 22587277
TI  - Twofold spontaneous symmetry breaking in the heavy-fermion superconductor UPt3.
AB  - The field-orientation dependent thermal conductivity of the heavy-fermion
      superconductor UPt3 was measured down to very low temperatures and under magnetic
      fields throughout the distinct superconducting phases: B and C phases. In the C
      phase, a striking twofold oscillation of the thermal conductivity within the
      basal plane is resolved reflecting the superconducting gap structure with a line
      of node along the a axis. Moreover, we find an abrupt vanishing of the
      oscillation across a transition to the B phase, as a clear indication of a change
      of gap symmetries. We also identify extra two line nodes below and above the
      equator in both B and C phases. From these results together with the symmetry
      consideration, the gap function of UPt3 is determined as a E(1u) representation
      characterized by a combination of two line nodes at the tropics and point nodes
      at the poles.

PMID- 22587278
TI  - Field-induced negative differential spin lifetime in silicon.
AB  - We show that the electric-field-induced thermal asymmetry between the electron
      and lattice systems in pure silicon substantially impacts the identity of the
      dominant spin relaxation mechanism. Comparison of empirical results from long
      distance spin transport devices with detailed Monte Carlo simulations confirms a
      strong spin depolarization beyond what is expected from the standard Elliott
      Yafet theory even at low temperatures. The enhanced spin-flip mechanism is
      attributed to phonon emission processes during which electrons are scattered
      between conduction band valleys that reside on different crystal axes. This leads
      to anomalous behavior, where (beyond a critical field) reduction of the transit
      time between spin-injector and spin-detector is accompanied by a counterintuitive
      reduction in spin polarization and an apparent negative spin lifetime.

PMID- 22587279
TI  - Refining the spin Hamiltonian in the spin-1/2 kagome lattice antiferromagnet
      ZnCu3(OH)6Cl2 using single crystals.
AB  - We report thermodynamic measurements of the S=1/2 kagome lattice antiferromagnet
      ZnCu3(OH)6Cl2, a promising candidate system with a spin-liquid ground state.
      Using single crystal samples, the magnetic susceptibility both perpendicular and
      parallel to the kagome plane has been measured. A small, temperature-dependent
      anisotropy has been observed, where chi(z)/chi(p)>1 at high temperatures and
      chi(z)/chi(p)<1 at low temperatures. Fits of the high-temperature data to a Curie
      Weiss model also reveal an anisotropy. By comparing with theoretical
      calculations, the presence of a small easy-axis exchange anisotropy can be
      deduced as the primary perturbation to the dominant Heisenberg nearest neighbor
      interaction. These results have great bearing on the interpretation of
      theoretical calculations based on the kagome Heisenberg antiferromagnet model to
      the experiments on ZnCu3(OH)6Cl2.

PMID- 22587280
TI  - Ultrafast alpha-like relaxation of a fragile glass-forming liquid measured using
      two-dimensional infrared spectroscopy.
AB  - Ultrafast two-dimensional infrared (2D-IR) spectroscopy is used to study the
      picosecond dynamics of a vibrational probe molecule dissolved in a fragile glass
      former. The spectral dynamics are observed as the system is cooled to within a
      few degrees of the glass transition temperature (T(g)). We observe nonexponential
      relaxation of the frequency-frequency correlation function, similar to what has
      been reported for other dynamical correlation functions. In addition, we see
      evidence for alpha-like relaxation, typically associated with long-time,
      cooperative molecular motion, on the ultrafast time scale. The data suggests that
      the spectral dynamics are sensitive to cooperative motion occurring on time
      scales that are necessarily longer than the observation time.

PMID- 22587281
TI  - Room-temperature laser emission of ZnO nanowires explained by many-body theory.
AB  - Are excitons involved in lasing in ZnO nanowires or not? Our recently developed
      and experimentally tested quantum many-body theory sheds new light on this
      question. We measured the laser thresholds and Fabry-Perot laser modes for three
      radically different excitation schemes. The thresholds, photon energies, and mode
      spacings can all be explained by our theory, without invoking enhanced light
      matter interaction, as is needed in an earlier excitonic model. Our conclusion is
      that lasing in ZnO nanowires at room temperature is not of excitonic nature, as
      is often thought, but instead is electron-hole plasma lasing.

PMID- 22587282
TI  - Coherent control of the route of an ultrafast magnetic phase transition via low
      amplitude spin precession.
AB  - Time-resolved magneto-optical imaging of laser-excited rare-earth orthoferrite
      (SmPr)FeO3 demonstrates that a single 60 fs circularly polarized laser pulse is
      capable of creating a magnetic domain on a picosecond time scale with a
      magnetization direction determined by the helicity of light. Depending on the
      light intensity and sample temperature, pulses of the same helicity can create
      domains with opposite magnetizations. We argue that this phenomenon relies on a
      twofold effect of light which (i) instantaneously excites coherent low-amplitude
      spin precession and (ii) triggers a spin reorientation phase transition. The
      former dynamically breaks the equivalence between two otherwise degenerate states
      with opposite magnetizations in the high-temperature phase and thus controls the
      route of the phase transition.

PMID- 22587283
TI  - Spin coherence during optical excitation of a single nitrogen-vacancy center in
      diamond.
AB  - We examine the quantum spin state of a single nitrogen-vacancy (NV) center in
      diamond at room temperature as it makes a transition from the orbital ground
      state (GS) to the orbital excited state (ES) during nonresonant optical
      excitation. While the fluorescence readout of NV-center spins relies on
      conservation of the longitudinal spin projection during optical excitation, the
      question of quantum phase preservation has not been examined. Using Ramsey
      measurements and quantum process tomography of the optical excitation process, we
      measure a trace fidelity of F=0.87+/-0.03, which includes ES spin dephasing
      during measurement. Extrapolation to the moment of optical excitation yields
      F~0.95. This result provides insight into the interaction between spin coherence
      and nonresonant optical absorption through a vibronic sideband.

PMID- 22587284
TI  - Polar antiferromagnets produced with orbital order.
AB  - Polar states are realized in pseudocubic manganite films fabricated on high-index
      substrates, in which a Jahn-Teller (JT) distortion remains an active variable.
      Several types of orbital orders (OOs) were found to develop large optical second
      harmonics, signaling broken-inversion symmetry distinct from their bulk forms and
      films on (100) substrates. The observed symmetry lifting and first-principles
      calculation both indicate that the modified JT q2 mode drives Mn-site off
      centering, which can be controlled by a magnetic-field-induced phase transition
      via a coupling of OO and spin orders.

PMID- 22587285
TI  - Substrate clamping effects on irreversible domain wall dynamics in lead zirconate
      titanate thin films.
AB  - The role of long-range strain interactions on domain wall dynamics is explored
      through macroscopic and local measurements of nonlinear behavior in mechanically
      clamped and released polycrystalline lead zirconate-titanate (PZT) films.
      Released films show a dramatic change in the global dielectric nonlinearity and
      its frequency dependence as a function of mechanical clamping. Furthermore, we
      observe a transition from strong clustering of the nonlinear response for the
      clamped case to almost uniform nonlinearity for the released film. This behavior
      is ascribed to increased mobility of domain walls. These results suggest the
      dominant role of collective strain interactions mediated by the local and global
      mechanical boundary conditions on the domain wall dynamics. The work presented in
      this Letter demonstrates that measurements on clamped films may considerably
      underestimate the piezoelectric coefficients and coupling constants of released
      structures used in microelectromechanical systems, energy harvesting systems, and
      microrobots.

PMID- 22587286
TI  - Bifurcation analysis of the transition of dune shapes under a unidirectional
      wind.
AB  - A bifurcation analysis of dune shape transition is made. By use of a reduced
      model of dune morphodynamics, the Dune Skeleton model, we elucidate the
      transition mechanism between different shapes of dunes under unidirectional wind.
      It was found that the decrease in the total amount of sand in the system and/or
      the lateral sand flow shifts the stable state from a straight transverse dune to
      a wavy transverse dune through a pitchfork bifurcation. A further decrease causes
      wavy transverse dunes to shift into barchans through a Hopf bifurcation. These
      bifurcation structures reveal the transition mechanism of dune shapes under
      unidirectional wind.

PMID- 22587287
TI  - Bistability and spatiotemporal irregularity in neuronal networks with nonlinear
      synaptic transmission.
AB  - We present a mean-field theory for spiking networks operating in the balanced
      excitation-inhibition regime, with synapses displaying short-term plasticity. The
      theory reveals a novel mechanism for bistability which relies on the nonlinearity
      of the synaptic interactions. As synaptic nonlinearity is mainly controlled by
      the spiking rates, the different states are stabilized by dynamically generated
      changes in the noise level. Thus, in both states, the network operates in the
      fluctuation-driven regime, producing activity patterns characterized by strong
      spatiotemporal irregularity.

PMID- 22587288
TI  - Two-dimensional x-ray beam phase sensing.
AB  - We present a new method to analyze quantitatively the wave front of a partially
      coherent x-ray beam. The technique is based on the use of two-dimensional speckle
      patterns combined with digital image correlation algorithms and offers a pixel
      size resolution, a high accuracy, and a reduced sensitivity to mechanical
      vibrations thanks to a very simple setup. The requirements on transverse and
      longitudinal coherence are also low. Finally, we show how the method can be used
      for phase contrast imaging applications by a single sample exposure process.

PMID- 22587289
TI  - Critical behavior and axis defining symmetry breaking in Hydra embryonic
      development.
AB  - The formation of a hollow cellular sphere is often one of the first steps of
      multicellular embryonic development. In the case of Hydra, the sphere breaks its
      initial symmetry to form a foot-head axis. During this process a gene, ks1, is
      increasingly expressed in localized cell domains whose size distribution becomes
      scale-free at the axis-locking moment. We show that a physical model based solely
      on the production and exchange of ks1-promoting factors among neighboring cells
      robustly reproduces the scaling behavior as well as the experimentally observed
      spontaneous and temperature-directed symmetry breaking.

PMID- 22587290
TI  - Emergence of fairness in repeated group interactions.
AB  - Often groups need to meet repeatedly before a decision is reached. Hence, most
      individual decisions will be contingent on decisions taken previously by others.
      In particular, the decision to cooperate or not will depend on one's own
      assessment of what constitutes a fair group outcome. Making use of a repeated N
      person prisoner's dilemma, we show that reciprocation towards groups opens a
      window of opportunity for cooperation to thrive, leading populations to engage in
      dynamics involving both coordination and coexistence, and characterized by cycles
      of cooperation and defection. Furthermore, we show that this process leads to the
      emergence of fairness, whose level will depend on the dilemma at stake.

PMID- 22587291
TI  - Evolutionary dynamics of restriction site avoidance.
AB  - Molecular noise in bacterial restriction-modification systems can cause rare
      events of host DNA cleavage at restriction sites. Such noise-induced selective
      pressure may result in evolved sequences exhibiting restriction site avoidance.
      We identify a two-state regime of evolutionary dynamics, in which populations
      either develop avoidance or go extinct. Using perturbation theory, we show that
      equilibrium sequence statistics exhibit power-law scaling in the ratio of
      restriction strength to mutation rate. Noise levels comparable to mutation rates
      can be sufficient to evolve detectable avoidance.

PMID- 22587292
TI  - Role of cellulose oxidation in the yellowing of ancient paper.
AB  - The yellowing of paper on aging causes major aesthetic damages of cultural
      heritage. It is due to cellulose oxidation, a complex process with many possible
      products still to be clarified. By comparing ultraviolet-visible reflectance
      spectra of ancient and artificially aged modern papers with ab initio time
      dependent density functional theory calculations, we identify and estimate the
      abundance of oxidized functional groups acting as chromophores and responsible of
      paper yellowing. This knowledge can be used to set up strategies and selective
      chemical treatments preventing paper yellowing.

PMID- 22587293
TI  - Comment on "Magnetic-field-tuned quantum phase transition in the insulating
      regime of ultrathin amorphous Bi films".

PMID- 22587297
TI  - Fourth Conversation in the Discipline: Biomolecular Stereodynamics State
      University of New York at Albany, June 4-8, 1985.

PMID- 22587299
TI  - Erratum.

PMID- 22587300
TI  - Statin pleiotropy prevents rho kinase-mediated intestinal epithelial barrier
      compromise induced by Blastocystis cysteine proteases.
AB  - Blastocystis is an enteric parasite that causes acute and chronic intestinal
      infections, often non-responsive to conventional antibiotics. The effects of
      Blastocystis infections on human epithelial permeability are not known, and
      molecular mechanisms of Blastocystis-induced intestinal pathology remain unclear.
      This study was conducted to determine whether Blastocystis species alters human
      intestinal epithelial permeability, to assess whether these abnormalities are rho
      kinase (ROCK)-dependent, and to investigate the therapeutic potential of the HMG
      CoA reductase inhibitor Simvastatin in altered intestinal epithelial barrier
      function. The effect of metronidazole resistant (Mz(r)) Blastocystis isolated
      from a symptomatic patient on human colonic epithelial monolayers (Caco-2) was
      assessed. Modulation of enterocyte myosin light chain phosphorylation,
      transepithelial fluorescein isothiocyanate-dextran fluxes, transepithelial
      resistance, cytoskeletal F-actin and tight junctional zonula occludens-1 (ZO-1)
      by parasite cysteine proteases were measured in the presence or absence of HMG
      CoA reductase and ROCK inhibition. Blastocystis significantly decreased
      transepithelial resistance, increased epithelial permeability, phosphorylated
      myosin light chain and reorganized epithelial actin cytoskeleton and ZO-1. These
      alterations were abolished by inhibition of enterocyte ROCK, HMG-CoA reductase
      and parasite cysteine protease. Our findings suggest that cysteine proteases of
      Mz(r) Blastocystis induce ROCK-dependent disruption of intestinal epithelial
      barrier function and correlates with reorganization of cytoskeletal F-actin and
      tight junctional ZO-1. Simvastatin prevented parasite-induced barrier-compromise,
      suggesting a therapeutic potential of statins in intestinal infections.

PMID- 22587301
TI  - Genetic factors associated with small for gestational age birth and the use of
      human growth hormone in treating the disorder.
AB  - The term small for gestational age (SGA) refers to infants whose birth weights
      and/or lengths are at least two standard deviation (SD) units less than the mean
      for gestational age. This condition affects approximately 3%-10% of newborns.
      Causes for SGA birth include environmental factors, placental factors such as
      abnormal uteroplacental blood flow, and inherited genetic mutations. In the past
      two decades, an enhanced understanding of genetics has identified several
      potential causes for SGA. These include mutations that affect the growth hormone
      (GH)/insulin-like growth factor (IGF)-1 axis, including mutations in the IGF-1
      gene and acid-labile subunit (ALS) deficiency. In addition, select polymorphisms
      observed in patients with SGA include those involved in genes associated with
      obesity, type 2 diabetes, hypertension, ischemic heart disease and deletion of
      exon 3 growth hormone receptor (d3-GHR) polymorphism. Uniparental disomy (UPD)
      and imprinting effects may also underlie some of the phenotypes observed in SGA
      individuals. The variety of genetic mutations associated with SGA births helps
      explain the diversity of phenotype characteristics, such as impaired motor or
      mental development, present in individuals with this disorder. Predicting the
      effectiveness of recombinant human GH (hGH) therapy for each type of mutation
      remains challenging. Factors affecting response to hGH therapy include the dose
      and method of hGH administration as well as the age of initiation of hGH therapy.
      This article reviews the results of these studies and summarizes the success of
      hGH therapy in treating this difficult and genetically heterogenous disorder.

PMID- 22587302
TI  - Conjugated microporous polymers as molecular sensing devices: microporous
      architecture enables rapid response and enhances sensitivity in fluorescence-on
      and fluorescence-off sensing.
AB  - Conjugated polymers are attractive materials for the detection of chemicals
      because of their remarkable pi-conjugation and photoluminescence properties. In
      this article, we report a new strategy for the construction of molecular
      detection systems with conjugated microporous polymers (CMPs). The condensation
      of a carbazole derivative, TCB, leads to the synthesis of a conjugated
      microporous polymer (TCB-CMP) that exhibits blue luminescence and possesses a
      large surface area. Compared with a linear polymer analogue, TCB-CMP showed
      enhanced detection sensitivity and allowed for the rapid detection of arenes upon
      exposure to their vapors. TCB-CMP displayed prominent fluorescence enhancement in
      the presence of electron-rich arene vapors and drastic fluorescence quenching in
      the presence of electron-deficient arene vapors, and it could be reused without a
      loss of sensitivity and responsiveness. These characteristics are attributed to
      the microporous conjugated network of the material. Specifically, the micropores
      absorb arene molecules into the confined space of the polymer, the skeleton
      possesses a large surface area and provides a broad interface for arenes, and the
      network architecture facilitates exciton migration over the framework. These
      structural features function cooperatively, enhancing the signaling activity of
      TCB-CMP in fluorescence-on and fluorescence-off detection.

PMID- 22587304
TI  - Chirality measures of alpha-amino acids.
AB  - To measure molecular chirality, the molecule is treated as a finite set of points
      in the Euclidean R(3) space supplemented by k properties, p(1)((i)), p(2)((i)),
      ..., p(k)((i)) assigned to the ith atom, which constitute a point in the Property
      P(k) space. Chirality measures are described as the distance between a molecule
      and its mirror image minimized over all its arbitrary orientation-preserving
      isometries in the R(3) * P(k) Cartesian product space. Following this formalism,
      different chirality measures can be estimated by taking into consideration
      different sets of atomic properties. Here, for alpha-amino acid zwitterionic
      structures taken from the Cambridge Structural Database and for all 1684 neutral
      conformers of 19 biogenic alpha-amino acid molecules, except glycine and cystine,
      found at the B3LYP/6-31G** level, chirality measures have been calculated by a
      CHIMEA program written in this project. It is demonstrated that there is a
      significant correlation between the measures determined for the alpha-amino acid
      zwitterions in crystals and the neutral forms in the gas phase. Performance of
      the studied chirality measures with changes of the basis set and computation
      method was also checked. An exemplary quantitative structure-activity
      relationship (QSAR) application of the chirality measures was presented by an
      introductory model for the benchmark Cramer data set of steroidal ligands of the
      sex-hormone binding globulin.

PMID- 22587303
TI  - Dynamic metabolomics differentiates between carbon and energy starvation in
      recombinant Saccharomyces cerevisiae fermenting xylose.
AB  - BACKGROUND: The concerted effects of changes in gene expression due to changes in
      the environment are ultimately reflected in the metabolome. Dynamics of
      metabolite concentrations under a certain condition can therefore give a
      description of the cellular state with a high degree of functional information.
      We used this potential to evaluate the metabolic status of two recombinant
      strains of Saccharomyces cerevisiae during anaerobic batch fermentation of a
      glucose/xylose mixture. Two isogenic strains were studied, differing only in the
      pathways used for xylose assimilation: the oxidoreductive pathway with xylose
      reductase (XR) and xylitol dehydrogenase (XDH) or the isomerization pathway with
      xylose isomerase (XI). The isogenic relationship between the two strains
      ascertains that the observed responses are a result of the particular xylose
      pathway and not due to unknown changes in regulatory systems. An increased
      understanding of the physiological state of these strains is important for
      further development of efficient pentose-utilizing strains for bioethanol
      production. RESULTS: Using LC-MS/MS we determined the dynamics in the
      concentrations of intracellular metabolites in central carbon metabolism, nine
      amino acids, the purine nucleotides and redox cofactors. The general response to
      the transition from glucose to xylose was increased concentrations of amino acids
      and TCA-cycle intermediates, and decreased concentrations of sugar phosphates and
      redox cofactors. The two strains investigated had significantly different uptake
      rates of xylose which led to an enhanced response in the XI-strain. Despite the
      difference in xylose uptake rate, the adenylate energy charge remained high and
      stable around 0.8 in both strains. In contrast to the adenylate pool, large
      changes were observed in the guanylate pool. CONCLUSIONS: The low uptake of
      xylose by the XI-strain led to several distinguished responses: depletion of key
      metabolites in glycolysis and NADPH, a reduced GTP/GDP ratio and accumulation of
      PEP and aromatic amino acids. These changes are strong indicators of carbon
      starvation. The XR/XDH-strain displayed few such traits. The coexistence of these
      traits and a stable adenylate charge indicates that xylose supplies energy to the
      cells but does not suppress a response similar to carbon starvation. Particular
      signals may play a role in the latter, of which the GTP/GMP ratio could be a
      candidate as it decreased significantly in both strains.

PMID- 22587305
TI  - The partly epithelialized free gingival graft (pe-fgg) at lower incisors. A pilot
      study with implications for alignment of the mucogingival junction.
AB  - AIMS: A partly epithelialized free gingival graft (PE-FGG) is described for the
      treatment of isolated and multiple gingival recessions in lower incisors to
      improve root coverage potential and mucogingival junction (MGJ) alignment.
      METHODS: Twelve single gingival recessions in 12 patients and 16 multiple
      recessions in 7 patients at lower incisors were included. A FGG partly deprived
      of epithelium was harvested from the palate. The epithelialized coronal part of
      the graft extended from the CEJ to the "ideal" position of the MGJ of the
      recession site/s. The apical part of the PE-FGG deprived of the epithelium was
      inserted between the alveolar mucosal flap and the recipient bed periostium. An
      aesthetic evaluation was performed. RESULTS: Treatment resulted in 94 +/- 11% and
      96 +/- 11% root coverage and 75% and 87.5% of the treated teeth completely
      covered in the single recession and in the multiple recession groups
      respectively. The 1-year KT was associated with the baseline extent of the
      epithelialized part of the graft in both groups. As a consequence, the MGJ
      resulted in properly aligned teeth in 14 of 19 patients. Three independent
      clinicians assigned an aesthetic score ranging from 6.36 +/- 2.5 to 7.91 +/- 1.7
      in the single REC group and from 6.62 +/- 2.2 to 7.87 +/- 1.8 in the multiple REC
      group. CONCLUSIONS: The application of the M-FGG resulted in high percentage of
      recessions completely covered with excellent alignment of the MGJ and appreciable
      aesthetic outcomes.

PMID- 22587306
TI  - Layered graphitic carbon host formation during liquid-free solid state growth of
      metal pyrophosphates.
AB  - We report a successful ligand- and liquid-free solid state route to form metal
      pyrophosphates within a layered graphitic carbon matrix through a single step
      approach involving pyrolysis of previously synthesized organometallic derivatives
      of a cyclotriphosphazene. In this case, we show how single crystal Mn(2)P(2)O(7)
      can be formed on either the micro- or the nanoscale in the complete absence of
      solvents or solutions by an efficient combustion process using rationally
      designed macromolecular trimer precursors, and present evidence and a mechanism
      for layered graphite host formation. Using in situ Raman spectroscopy, infrared
      spectroscopy, X-ray diffraction, high resolution electron microscopy,
      thermogravimetric and differential scanning calorimetric analysis, and near-edge
      X-ray absorption fine structure examination, we monitor the formation process of
      a layered, graphitic carbon in the matrix. The identification of thermally and
      electrically conductive graphitic carbon host formation is important for the
      further development of this general ligand-free synthetic approach for inorganic
      nanocrystal growth in the solid state, and can be extended to form a range of
      transition metals pyrophosphates. For important energy storage applications, the
      method gives the ability to form oxide and (pyro)phosphates within a conductive,
      intercalation possible, graphitic carbon as host-guest composites directly on
      substrates for high rate Li-ion battery and emerging alternative positive
      electrode materials.

PMID- 22587307
TI  - Second-harmonic generation imaging of metal nano-objects with cylindrical vector
      beams.
AB  - We introduce an imaging technique based on second-harmonic generation with
      cylindrical vector beams that is extremely sensitive to three-dimensional
      orientation and nanoscale morphology of metal nano-objects. Our experiments and
      second-harmonic field calculations based on frequency-domain boundary element
      method are in very good agreement. The technique provides contrast for structural
      features that cannot be resolved by linear techniques or conventional states of
      polarization and shows great potential for simple and cost-effective far-field
      optical imaging in plasmonics.

PMID- 22587308
TI  - BDE261: a comprehensive set of high-level theoretical bond dissociation
      enthalpies.
AB  - We have used the high-level W1w protocol to compile a comprehensive collection of
      261 bond dissociation enthalpies (BDEs) for bonds connecting hydrogen, first-row
      and second-row p-block elements. Together they cover 45 bond types, and we term
      this the BDE261 set. We have used these benchmark values to assess the
      performance of computationally less demanding theoretical procedures, including
      density functional theory (DFT), double-hybrid DFT (DHDFT), and high-level
      composite procedures. We find that the M06-2X (DFT), ROB2-PLYP and DuT-D3
      (DHDFT), and G3X(MP2)-RAD and G4(MP2)-6X (composite) procedures yield absolute
      BDEs with satisfactory to excellent accuracy. Overall, we recommend G4(MP2)-6X as
      an accurate and relatively cost-effective procedure for the direct computation of
      BDEs. One important finding is that the deviations for DFT and (especially) DHDFT
      procedures are often quite systematic. This allows an alternative approach to
      obtaining accurate absolute BDEs, namely, to evaluate accurate relative BDEs
      (RBDEs) using a computationally less demanding procedure, and to use these RBDEs
      in combination with appropriate and accurate reference BDEs to give accurate
      absolute BDEs. We recommend DuT-D3 for this purpose. For a still less
      computationally demanding approach, we introduce the deviation from additivity of
      the RBDE (DARBDE), and demonstrate that the combination of lower-level DARBDEs
      for larger systems and higher-level (W1w) reference RBDEs and BDEs for small
      systems can be utilized to obtain improved RBDEs for multiply substituted systems
      at low cost.

PMID- 22587309
TI  - When competent isn't good enough.

PMID- 22587310
TI  - Improving suturing workshops using modern educational theory.
AB  - BACKGROUND: The teaching of practical skills such as venepuncture and suturing
      are important for medical students and junior doctors alike. Despite its
      importance, little time is devoted to its teaching on the undergraduate
      curriculum. Instead, the responsibility of skills teaching often falls to senior
      health care professionals. CONTEXT: At Aberdeen Royal Infirmary, clinicians have
      laid on 'after-work' skills workshops. One of the regularly run workshops is on
      basic suturing. Initially these sessions were run in a relatively ad-libbed and
      unprepared way. It was clear that these sessions were not as successful as they
      could be--with students failing to attain proficiency at the desired rate.
      INNOVATION: It was decided to adapt the suturing workshop by adhering to current
      theories in modern educational practice. Using the work of Gagne and others,
      small changes were made to the delivery of the workshop to see if this improved
      student outcome. IMPLICATIONS: Adapting the workshops using modern educational
      theory had two distinct benefits: the students enjoyed the sessions far more and
      attained proficiency in suturing more quickly. The article demonstrates how
      making small changes, which are not labour intensive, can dramatically improve
      the impact of a teaching session.

PMID- 22587311
TI  - New theory from an old technique: the Rolma matrices.
AB  - BACKGROUND: Understanding the reasons behind non-adherence to clinical practice
      guidelines is a complex process. Many explanatory models have been proposed that
      are grounded in qualitative theory. The 2 * 2 matrix has often been used to
      condense this potentially complex information into a format understandable to
      clinicians without educational or qualitative backgrounds. METHODS: The concept
      of tacit knowledge and its interplay with evidence-based practice is explored and
      the role of matrices in demonstrating various interactions is defined. RESULTS:
      Two new matrices are proposed to describe how experience and tacit knowledge may
      determine the outcome of patients, regardless of the evidence base. CONCLUSIONS:
      The Rolma 1 and 2 matrices can be used to demonstrate to all clinicians,
      regardless of their background, how their experiences effect judgements and why
      junior (and senior) staff may not appear to engage with best practice.

PMID- 22587312
TI  - Cadaveric surgery: a novel approach to teaching clinical anatomy.
AB  - INTRODUCTION: Anatomy is an essential basic science for safe and effective
      medical practice. In 2006 the UK Anatomy Act was changed to allow the use of
      surgical procedures on cadavers. This has unlocked opportunities for new methods
      of teaching clinically relevant anatomy. This study explores how surgical
      procedures may provide a purposeful and memorable way for undergraduates to learn
      anatomy, compared with conventional teaching methods. METHODS: Under supervision,
      a group of third-year medical students prepared for and then performed a shoulder
      hemi-arthroplasty after identifying key anatomical structures and surgical
      objectives. The procedure was performed in a simulated theatre environment. A
      focus group was used to collect qualitative data based on the learning
      experience. RESULTS: The surgical approach and implant insertion were
      successfully completed, and the educational objectives of identifying and
      learning surrounding structures were met. The focus group found that the exercise
      presented a relaxed introduction to surgery, enabled learning by association, and
      provided a learning experience that was both purposeful and complete. DISCUSSION:
      The preparation and completion of the procedure enabled the students to focus on
      the anatomy of the shoulder, by identifying and forming associations with
      surrounding structures. Uniquely, the surgical nature of this project also
      allowed undergraduate students to practice key surgical skills and principles.
      CONCLUSION: The authors believe that learning anatomy via a surgical approach
      provides a relevant, in-depth, purposeful and enjoyable learning experience. This
      technique also provided a valuable insight into surgery.

PMID- 22587313
TI  - evPaeds: undergraduate clinical reasoning.
AB  - BACKGROUND: Clinical reasoning is one of the most important skills that medical
      students need to develop. Our medical students learn clinical reasoning in small
      group discussion sessions and during their clinical attachments. We wanted to
      provide additional opportunities for them to develop these important skills.
      CONTEXT: Our undergraduate paediatric curriculum is based on 25 clinical
      presentations, and is delivered on the website myPaediatrics. We used simple show
      and-hide case examples in each presentation to illustrate to students how to use
      the knowledge and skills they acquire to solve the clinical presentations. These
      are popular with students but provide little opportunity for interaction.
      INNOVATION: Based on two commonly available formats for the virtual patient,
      neither of which had fully met the specific needs of our undergraduate students,
      we developed hybrid software: evPaeds. Close collaboration with students and
      teachers ensured that evPaeds met the unique learning needs of undergraduate
      students. evPaeds incorporates the Paediatric Decision Tree, which encourages
      students to make decisions on investigations and management, with immediate
      feedback. Explicitly referring to the basic sciences in our virtual patients
      resulted in them being valuable to students in both the pre-clinical and clinical
      years. IMPLICATIONS: evPaeds has proven popular with students to practise and
      develop clinical reasoning, individually or in small group sessions.

PMID- 22587314
TI  - Medicine in the community: a unique partnership.
AB  - INTRODUCTION: Many advantages to community-oriented medical education have
      already been described. Responding to reforms in undergraduate medical education
      policy, our medical school reconfigured its clinical curriculum to include a
      module with a broad community focus, based in primary and secondary care. We
      describe our initial experience developing, implementing and evaluating this
      module. METHODS: The aim of the module was to provide students with an
      understanding of medicine as practised, and health care as delivered, in the
      community. The 6-week module is delivered four times annually in the final stage
      of the medical degree programme, with 40-50 students attending each time.
      Learning experiences encompass clinical attachments, lectures, workshops,
      seminars and group presentations, with multifaceted assessment and formal student
      feedback at the end of the module (Ramsden's Module/Course Experience
      Questionnaire, and student self-assessment of specified learning objectives,
      using a five-point Likert scale). RESULTS OF STUDENT FEEDBACK: A total of 104 out
      of 181 (57.5%) students completed the evaluation. Of these, 69.3 per cent were
      satisfied with the course (with a mean Likert score of 3.7). More than 75 per
      cent of the students agreed or strongly agreed that they had attained 12 of 13
      specified learning objectives, and 64.6 per cent (95% CI 55.0-74.2%) agreed that
      they could use common diagnostic/therapeutic equipment. The mean Likert scores
      for Ramsden questionnaire subscales were: good teaching, 3.5; clarity of goals,
      3.1; appropriate assessment, 3.6; appropriate workload, 3.7; and generic skills
      development, 3.4. The most positive scores were attained for teachers' ability to
      explain (3.95; 77.5% agreed or strongly agreed) and effort at making subjects
      interesting (3.83; 73.5% agreed or strongly agreed). CONCLUSION: Our experience
      shows a community-based module with a strong combined primary care and elderly
      care focus is feasible, and enables the achievement of valuable learning
      objectives.

PMID- 22587315
TI  - DrivAbility: teaching medical aspects of driving.
AB  - CONTEXT: Teaching medical aspects of fitness to drive (FTD) is currently
      inconsistent across UK medical schools, with almost one-third of UK medical
      schools offering no tuition on medical aspects of FTD. It is, therefore, not
      surprising to find that medical students and doctors tend to lack confidence
      regarding the medical aspects of FTD and Driver and Vehicle Licensing Agency
      (DVLA) medical standards. INNOVATION: In response to this inconsistency we
      developed an innovative new learning module to teach our medical students the
      importance of giving appropriate advice to patients about driving, the role of
      the DVLA regarding medical aspects of FTD, how to recognise when patients should
      be referred to a driving assessment centre and what adaptations are available to
      allow patients with physical disabilities to drive safely. As far as we are aware
      Derby is the first centre in the world to incorporate the practical experience of
      driving adapted vehicles (at a driving assessment centre) into the undergraduate
      medical curriculum as an aid to teaching medical aspects of FTD. This practical
      learning module has proven popular with the students. IMPLICATIONS: Driving these
      adapted vehicles has allowed our students to appreciate some of the practical
      difficulties disabled drivers experience when learning new driving techniques.
      However, as only 18 driving assessment centres exist within the UK, an exact
      replication of this learning module will be limited elsewhere. Nevertheless, we
      would encourage other medical schools to evaluate the local resources that could
      enhance the delivery of their undergraduate curricula.

PMID- 22587316
TI  - Introducing medical students to prehospital care.
AB  - BACKGROUND: Studies show that prehospital care is an important, yet often
      neglected part of the medical undergraduate curriculum. Thus, the Prehospital
      Care Programme (PCP) was introduced at Barts and the London School of Medicine
      and Dentistry in 2008, aiming to expose medical undergraduates to this unique
      area of medicine. CONTEXT: The programme makes use of the links between the
      medical school and the London Ambulance Service (LAS) and the London Air
      Ambulance (LAA), and places students from Bachelor of Medicine and Bachelor of
      Surgery (MBBS) years 2-5 with mentors from these services during a series of
      working shifts. During shifts, students are assigned a set of learning objects
      and are instructed to complete a specially designed Student Report Form for each
      case that they observe. Students are recruited onto the programme at the end of
      MBBS year 1 through the submission of a CV and a written application. Shortlisted
      candidates are interviewed and those that are successful are invited to join the
      programme at the beginning of MBBS year 2. INNOVATION AND IMPLICATIONS: Interest
      in the programme has increased exponentially since it was introduced in 2008. It
      appeals to medical students who are enthusiastic about the field of Emergency
      Medicine and Prehospital Care, and offers them a unique opportunity to enhance
      their knowledge and experience. It also encourages students to develop generic
      skills, communication skills, interprofessionalism and record keeping.
      CONCLUSION: The PCP is a successful and immensely popular addition to the MBBS
      curriculum at Barts and the London School of Medicine and Dentistry. We hope to
      observe and continue to support similar replications at other medical schools.

PMID- 22587317
TI  - Training improves inter-collegial communication.
AB  - BACKGROUND: Good intercollegial communication is a relatively unstudied topic,
      although it is important for both health professionals and patients, contributing
      to enhanced well-being, self-awareness and integrity for health professionals,
      and positively affecting patient outcome and satisfaction. OBJECTIVE: To
      investigate whether a communication skills training course would improve
      intercollegial communication in an orthopaedic department. METHODS: The study was
      designed as an intervention study investigating the effectiveness of an in-house
      training course, evaluated by means of questionnaires. RESULTS: A total of
      177/181 (97.8%) participants answered the questionnaire before (T1), 165/169
      (97.6%) immediately after (T2) and 150/153 (98%) 6 months after the course (T3).
      Of six questions about intraprofessional communication, one and two questions
      were evaluated significantly higher at T2 and T3, respectively. Of the six
      questions about interprofessional communication, the increase was statistically
      significant for four questions in T2 and for five questions in T3, respectively.
      CONCLUSION: A communication skills training course improved health care
      professionals' assessment of intercollegial communication, and this was more
      pronounced in interprofessional rather than in intraprofessional communication,
      and was more pronounced 6 months after the training course than immediately after
      the training course. PRACTICE IMPLICATIONS: Communication skills training for
      health care professionals is recommended, and should also include all health care
      professions that have patient contact.

PMID- 22587318
TI  - Students developing resources for students.
AB  - BACKGROUND: The development of new technologies has provided medical education
      with the ability to enhance the student learning experience and meet the needs of
      changing curricula. Students quickly adapt to using multimedia learning
      resources, but these need to be well designed, learner-centred and interactive
      for students to become significantly engaged. CONTEXT: One way to ensure that
      students become committed users and that resources become distinct elements of
      the learning cycle is to involve students in resource design and production. Such
      an approach enables resources to accommodate student needs and preferences, but
      also provides opportunities for them to develop their own teaching and training
      skills. INNOVATION: The aim of the medical student research project was to design
      and produce an electronic resource that was focused on a particular anatomical
      region. The views of other medical students were used to decide what features
      were suitable for inclusion and the resulting package contained basic principles
      and clinical relevance, and used a variety of approaches such as images of
      cadaveric material, living anatomy movies and quizzes. The completed package was
      assessed using a survey matrix and found to compare well with commercially
      available products. IMPLICATIONS: Given the ever-diversifying arena of multimedia
      instruction and the ability of students to be fully conversant with technology,
      this project demonstrates that students are ideal participants and creators of
      multimedia resources. It is hoped that such an approach will help to further
      develop the skill base of students, but will also provide an avenue of developing
      packages that are student user friendly, and that are focused towards particular
      curricula requirements.

PMID- 22587319
TI  - Utility of a student-organised revision day.
AB  - BACKGROUND: Senior medical students organised and delivered a teaching day to
      prepare an academic year of junior colleagues for their end-of-year objective
      structured clinical examination (OSCE). METHODS: The day involved a series of
      mini lectures, followed by group-based teaching to reflect the various stations
      in the proceeding examinations. Feedback forms were completed at the start and
      end of the teaching day. RESULTS: As indicated through feedback, senior medical
      students are capable of organising a successful revision day to prepare more
      junior peers for their end-of-year examinations. DISCUSSION: Having completed the
      same set of assessments, senior medical students are well placed to prepare more
      junior colleagues for their examinations. This exercise offered valuable teaching
      experience for the tutors, and also highlighted numerous areas of development for
      future iterations. As found in other such projects, this approach was also rated
      as effective by the participants.

PMID- 22587320
TI  - Growth in empathy during clinical exchange.

PMID- 22587321
TI  - Clinical teaching.

PMID- 22587325
TI  - Interactive lecturing: a student perspective.

PMID- 22587326
TI  - Is sleeping in lectures a professionalism issue?

PMID- 22587328
TI  - Spatio-temporal pattern of programmed cell death in the developing Drosophila
      optic lobe.
AB  - A large number of cells die via programmed cell death during the normal
      development of the Drosophila optic lobe. In this study, we report the precise
      spatial and temporal pattern of cell death in this organ. Cell death in the
      developing optic lobe occurs in two distinct phases. The first phase extends from
      the start of metamorphosis to the mid-pupal stage. During this phase, a large
      number of cells die in the optic lobe as a whole, with a peak of cell death at an
      early pupal stage in the lamina and medulla cortices and the region of the
      T2/T3/C neurons, and a smaller number of dead cells observed in the lobula plate
      cortex. The second phase extends from the mid-pupal stage to eclosion. Throughout
      this period, a small number of dying cells can be observed, with a small peak at
      a late pupal stage. Most of the dying cells are neurons. During the first phase,
      dying cells are distributed in specific patterns in cortices. The lamina cortex
      contains two distinct clusters of dying cells; the medulla cortex, four clusters;
      the lobula plate cortex, one cluster; and the region of the T2/T3/C neurons, one
      cluster. Many of the clusters maintain their distinct positions in the optic lobe
      but others extend the region they cover during development. The presence of
      distinct clusters of dying cells at different phases suggests that distinct
      mechanisms control cell death during different stages of optic lobe development
      in Drosophila.

PMID- 22587330
TI  - Investigation of the local structure of mixtures of an ionic liquid with polar
      molecular species through molecular dynamics: cluster formation and angular
      distributions.
AB  - In this work, we used molecular dynamics simulations to analyze in detail the
      spatial distributions of the different constituents in mixtures of 1-butyl-3
      methylimidazolium tetrafluoroborate with three polar molecular species: water and
      two alcohols of different chain lengths (methanol and ethanol). In particular, we
      report results regarding the influence of the chosen species and its
      concentration on the formation of ionic and molecular clusters over the whole
      miscibility range, as well as on the angular distribution of polar molecules
      around the anion and the cation in these systems. Both analyses showed that
      addition of a molecular species breaks down the polar network of the pure ionic
      liquid in clusters whose mean size decreases progressively as more molecules are
      added. At very high concentrations of the molecular species, the ions are found
      to be isolated in mixtures with water and methanol, but they tend to form pairs
      in ethanol. In mixtures with water we identified large clusters that form a water
      network at very high water concentrations, while at low water concentrations
      polar molecules tend to form smaller aggregates. In contrast, in mixtures with
      alkanols there is no evidence of the formation of large alcohol clusters at any
      concentration. Spatial order in alcohol was also studied by means of the Kirkwood
      G factor, reaching the conclusion that the angular correlations which appear in
      pure alcohols due to dipole interactions are destroyed by the ionic liquid, even
      when present only in tiny amounts.

PMID- 22587329
TI  - Identification of 3'UTR sequence elements and a teloplasm localization motif
      sufficient for the localization of Hro-twist mRNA to the zygotic animal and
      vegetal poles.
AB  - The early localization of mRNA transcripts is critical in sorting cell fate
      determinants in the developing embryo. In the glossiphoniid leech, Helobdella
      robusta, maternal mRNAs, such as Hro-twist, localize to the zygotic teloplasm.
      Ten seven nucleotide repeat elements (AAUAAUA) called ARE2 and a predicted
      secondary structural motif, called teloplasm localization motif (TLM), are
      present in the 3'UTR of Hro-twist mRNA. We used site-directed mutagenesis,
      deletions, and microinjection of labeled, exogenous transcripts to determine if
      ARE2 elements, and the TLM, play a role in Hro-twist mRNA localization. Deleting
      the poly-A tail and the cytoplasmic polyadenylation element (CPE) had no effect
      on Hro-twist mRNA localization. Site-directed mutagenesis of nucleotides that
      altered ARE2 element sequences or the TLM suggest that the ARE2 elements and the
      TLM are important for Hro-twist mRNA localization to the teloplasm of pre
      cleavage zygotes. Hro-Twist protein expression data suggest that the localization
      of Hro-twist transcripts in zygotes and stage two embryos is not involved in
      ensuring mesoderm specification, as Hro-Twist protein is expressed uniformly in
      most cells before gastrulation. Our data may support a shared molecular mechanism
      for leech transcripts that localize to the teloplasm.

PMID- 22587331
TI  - Effects of the novel mitochondrial protein mimitin in insulin-secreting cells.
AB  - Mimitin, a novel mitochondrial protein, has been shown to act as a molecular
      chaperone for the mitochondrial complex I and to regulate ATP synthesis. During
      Type 1 diabetes development, pro-inflammatory cytokines induce mitochondrial
      damage in pancreatic beta-cells, inhibit ATP synthesis and reduce glucose-induced
      insulin secretion. Mimitin was expressed in rat pancreatic islets including beta
      cells and decreased by cytokines. In the ob/ob mouse, a model of insulin
      resistance and obesity, mimitin expression was down-regulated in liver and brain,
      up-regulated in heart and kidney, but not affected in islets. To further analyse
      the impact of mimitin on beta-cell function, two beta-cell lines, one with a low
      (INS1E) and another with a higher (MIN6) mimitin expression were studied. Mimitin
      overexpression protected INS1E cells against cytokine-induced caspase 3
      activation, mitochondrial membrane potential reduction and ATP production
      inhibition, independently from the NF-kappaB (nuclear factor kappaB)-iNOS
      (inducible NO synthase) pathway. Mimitin overexpression increased basal and
      glucose-induced insulin secretion and prevented cytokine-mediated suppression of
      insulin secretion. Mimitin knockdown in MIN6 cells had opposite effects to those
      observed after overexpression. Thus mimitin has the capacity to modulate
      pancreatic islet function and to reduce cytokine toxicity.

PMID- 22587332
TI  - Plasma levels of lipometabolism-related miR-122 and miR-370 are increased in
      patients with hyperlipidemia and associated with coronary artery disease.
AB  - BACKGROUND: Hyperlipidemia plays a crucial role in the development and
      progression of coronary artery disease (CAD). Recent studies have identified that
      microRNAs (miRNAs) are important regulators of lipid metabolism, but little is
      known about the circulating levels of lipometabolism-related miRNAs and their
      relationship with the presence of CAD in patients with hyperlipidemia. METHODS:
      In the present study, we enrolled a total of 255 hyperlipidemia patients with or
      without CAD and 100 controls with normal blood lipids. The plasma levels of four
      known lipometabolism-related miRNAs, miR-122, miR-370, miR-33a, and miR-33b were
      quantified by real-time quantitative PCR. Blood levels of total cholesterol (TC),
      triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and high density
      lipoprotein cholesterol were determined. Furthermore, the severity of CAD was
      assessed with the Gensini score system based on the degree of luminal narrowing
      and its geographic importance. RESULTS: Our results revealed for the first time
      that plasma levels of miR-122 and miR-370 were significantly increased in
      hyperlipidemia patients compared with controls, and the levels of miR-122 and miR
      370 were positively correlated with TC, TG, and LDL-C levels in both
      hyperlipidemia patients and controls. Multiple logistic regression analysis
      demonstrated that the increased levels of miR-122 and miR-370 were associated
      with CAD presence, even after adjustment for other cardiovascular risk factors.
      Furthermore, miR-122 and miR-370 levels were positively correlated with the
      severity of CAD quantified by the Gensini score. However, both miR-33a and miR
      33b were undetectable in plasma. CONCLUSIONS: Our results suggest that increased
      plasma levels of miR-122 and miR-370 might be associated with the presence as
      well as the severity of CAD in hyperlipidemia patients.

PMID- 22587333
TI  - Structural remodeling of the mouse gracilis artery: coordinated changes in
      diameter and medial area maintain circumferential stress.
AB  - OBJECTIVE: Vascular networks respond to chronic alterations in blood supply by
      structural remodeling. Previously, we showed that blood flow changes in the mouse
      GA lead to transient diameter increases, which can generate large increases in
      circumferential wall stress. Here, we examine the associated changes in the
      medial area of the arterial wall and the effects on circumferential wall stress.
      METHODS: To induce blood flow changes, one of the two feeding vessels to the GA
      was surgically removed. At 7-56 days after blood flow interruption, the
      vasculature was perfused with India ink for morphological measurements, and
      processed for immuno-cytochemistry to mark the medial cross-section area.
      Theoretical simulations of hemodynamics were used to analyze the data. RESULTS:
      During adaptive increases in vessel diameter, increases in medial area were
      observed, most strongly in the middle region of the artery. Simulations showed
      that this increase in medial area limits the increase in estimated
      circumferential stress during vascular adaptation to less than 50%, in contrast
      to an increase of up to 250% if the medial area had remained unchanged.
      CONCLUSIONS: During vascular adaptation, increases in circumferential stress are
      limited by growth of the media coordinated with diameter changes.

PMID- 22587334
TI  - Anaemia treatment in chronically dialysed children: a multicentre nationwide
      observational study.
AB  - OBJECTIVE: Erythropoiesis-stimulating agents (ESAs) are applied as a standard
      therapy in children with anaemia in chronic kidney disease. The aim of this study
      was to describe the efficacy and details of ESA treatment in a population of
      dialysed children in Poland. MATERIAL AND METHODS: The study had a prospective
      observational design and was performed in 12 dialysis centres. The study group
      comprised 117 dialysed children with a mean age at enrolment of 165.33 (97.18
      196.45) months. RESULTS: Dialysed children were treated mostly with epoietin beta
      and darbepoietin. The mean dose of ESA was 99 (68-147) U/kg/week with a
      significant difference between patients on peritoneal dialysis [83 (54-115)] and
      haemodialysis [134 (103-186)] (p < 0.0001). The mean haemoglobin of all the time
      point tests during 6 months was 10.91 +/- 1.18 g/dl. The efficacy of anaemia
      treatment was unsatisfactory in 52% of subjects. In multivariate analysis,
      initial haemoglobin level <10 g/l, any infection, younger age at first dialysis,
      malnutrition and inadequate ESA dosage remained significant predictors of
      anaemia. CONCLUSIONS: The study revealed that anaemia treatment in Polish
      children is unsatisfactory. Late commencement of the treatment, inadequate
      dosing, malnutrition and infections could constitute risk factors for therapy
      failure.

PMID- 22587335
TI  - Microscopical and chemical surface characterization of the gingival portion and
      connection of an internal hexagon abutment before and after different technical
      stages of preparation.
AB  - AIM: This study was aimed to assess contaminants on the abutment surface close to
      the implant-abutment interface and the connection, after common technical
      protocols. MATERIALS AND METHODS: A total of 40 abutments were divided into four
      groups: control group (abutment removed from the plastic envelop), test group1
      (milled), test group2 (milled and polished), test group3 (milled, polished and
      steamed). Groups were subjected to scanning electron microscope (SEM) analysis.
      Pollution particles were counted and measured. Mean values and standard deviation
      (SD) were calculated. To evaluate any difference between groups Wilcoxon Signed
      Rank Test was conducted. In addition, contaminant chemical characterization was
      investigated by Energy-dispersive X-ray spectroscopy (EDX). RESULTS: Control
      group presented minimal amount of pollution (mean value of 2.1 spots [SD: 1.66]
      covering 0.004% of the surface). On the other hand, SEM analysis revealed on the
      abutment surface a mean value of 115.9 (SD: 32.27), 162 (SD: 21.17), and 32.5
      (SD: 9.73) spots, respectively, in Test group 1, 2, and 3. Micro-particles
      covered the 0.025%, 0.057%, 0.0404% of the surface, respectively, in Test group
      1, 2, and 3. On the connection, SEM analysis revealed a mean value of 61.9 (SD:
      9.07), 39 (SD: 12.35), 42.1 (SD: 8.59) spots, respectively, in Test group 1, 2,
      and 3. Micro-particles covered the 0.0774%, 0.0869%, and 0.0392% of the surface,
      respectively, in Test group 1, 2, and 3. Spots were identified by EDX as micro
      particles of lubricant and titanium smear layer. All differences were
      statistically significant. CONCLUSIONS: After technical procedures, presence of
      contaminants on the abutment surface in contact with the peri-implant tissues was
      confirmed. To prevent that such debris could interfere with biological stability
      of peri-implant tissues and, thus, enhance the implant-prosthesis integration,
      different cleaning protocols should be evaluated.

PMID- 22587336
TI  - Grasp modelling with a biomechanical model of the hand.
AB  - The use of a biomechanical model for human grasp modelling is presented. A
      previously validated biomechanical model of the hand has been used. The
      equilibrium of the grasped object was added to the model through the
      consideration of a soft contact model. A grasping posture generation algorithm
      was also incorporated into the model. All the geometry was represented using a
      spherical extension of polytopes (s-topes) for efficient collision detection. The
      model was used to simulate an experiment in which a subject was asked to grasp
      two cylinders of different diameters and weights. Different objective functions
      were checked to solve the indeterminate problem. The normal finger forces
      estimated by the model were compared to those experimentally measured. The
      popular objective function sum of the squared muscle stresses was shown not
      suitable for the grasping simulation, requiring at least being complemented by
      task-dependent grasp quality measures.

PMID- 22587337
TI  - Adaptive molecular evolution of a defence gene in sexual but not functionally
      asexual evening primroses.
AB  - Theory predicts that sexual reproduction provides evolutionary advantages over
      asexual reproduction by reducing mutational load and increasing adaptive
      potential. Here, we test the latter prediction in the context of plant defences
      against pathogens because pathogens frequently reduce plant fitness and drive the
      evolution of plant defences. Specifically, we ask whether sexual evening primrose
      plant lineages (Onagraceae) have faster rates of adaptive molecular evolution and
      altered gene expression of a class I chitinase, a gene implicated in defence
      against pathogens, than functionally asexual evening primrose lineages. We found
      that the ratio of amino acid to silent substitutions (K(a) /K(s) = 0.19 vs. 0.11
      for sexual and asexual lineages, respectively), the number of sites identified to
      be under positive selection (four vs. zero for sexual and asexual lineages,
      respectively) and the expression of chitinase were all higher in sexual than in
      asexual lineages. Our results are congruent with the conclusion that a loss of
      sexual recombination and segregation in the Onagraceae negatively affects
      adaptive structural and potentially regulatory evolution of a plant defence
      protein.

PMID- 22587338
TI  - Development of normal-suction boundary control method based on inflow cannula
      pressure waveform for the undulation pump ventricular assist device.
AB  - It is desirable to obtain the maximum assist without suction in ventricular
      assist devices (VADs). However, high driving power of a VAD may cause severe
      ventricle suction that can induce arrhythmia, hemolysis, and pump damage. In this
      report, an appropriate VAD driving level that maximizes the assist effect without
      severe systolic suction was explored. The target driving level was set at the
      boundary between low driving power without suction and high driving power with
      frequent suction. In the boundary range, intermittent mild suction may occur.
      Driving power was regulated by the suction occurrence. The normal-suction
      boundary control method was evaluated in a female goat implanted with an
      undulation pump ventricular assist device (UPVAD). The UPVAD was driven in a
      semipulsatile mode with heartbeat synchronization control. Systolic driving power
      was adjusted using a normal-suction boundary control method developed for this
      study. We confirmed that driving power could be maintained in the boundary range.
      Occurrences of suction were evaluated using the suction ratio. We defined this
      ratio as the number of suction occurrences divided by the number of heartbeats.
      The suction ratio decreased by 70% when the normal-suction boundary control
      method was used.

PMID- 22587339
TI  - Comprehensive analysis of the effects of CdSe quantum dot size, surface charge,
      and functionalization on primary human lung cells.
AB  - The growing potential of quantum dots (QDs) in applications as diverse as
      biomedicine and energy has provoked much dialogue about their conceivable impact
      on human health and the environment at large. Consequently, there has been an
      urgent need to understand their interaction with biological systems. Parameters
      such as size, composition, surface charge, and functionalization can be modified
      in ways to either enhance biocompatibility or reduce their deleterious effects.
      In the current study, we simultaneously compared the impact of size, charge, and
      functionalization alone or in combination on biological responses using primary
      normal human bronchial epithelial cells. Using a suite of cellular end points and
      gene expression analysis, we determined the biological impact of each of these
      properties. Our results suggest that positively charged QDs are significantly
      more cytotoxic compared to negative QDs. Furthermore, while QDs functionalized
      with long ligands were found to be more cytotoxic than those functionalized with
      short ligands, negative QDs functionalized with long ligands also demonstrated
      size-dependent cytotoxicity. We conclude that QD-elicited cytotoxicity is not a
      function of a single property but a combination of factors. The mechanism of
      toxicity was found to be independent of reactive oxygen species formation, as
      cellular viability could not be rescued in the presence of the antioxidant n
      acetyl cysteine. Further exploring these responses at the molecular level, we
      found that the relatively benign negative QDs increased gene expression of
      proinflammatory cytokines and those associated with DNA damage, while the highly
      toxic positive QDs induced changes in genes associated with mitochondrial
      function. In an attempt to tentatively "rank" the contribution of each property
      in the observed QD-induced responses, we concluded that QD charge and ligand
      length, and to a lesser extent, size, are key factors that should be considered
      when engineering nanomaterials with minimal bioimpact (charge > functionalization
      > size).

PMID- 22587340
TI  - Effect of aging on optical quality and intraocular scattering using the double
      pass instrument.
AB  - PURPOSE: To assess the effect of aging on optical quality in a normal population.
      METHODS: We prospectively examined 100 normal eyes of 100 healthy volunteers (50
      men, 50 women; ages, 20-69 years; mean age +/- standard deviation, 44.6 +/- 15.5
      years). We quantitatively assessed the values of MTF cutoff frequency, Strehl
      ratio, and objective scattering index (OSI), using an Optical Quality Analysis
      SystemTM (Visiometrics, Terrassa, Spain). We took these measurements three times
      each, and the mean value obtained was used for statistical analysis. We
      investigated the relationships between subject age and these optical quality
      parameters. RESULTS: The mean MTF cutoff frequency, Strehl ratio, and OSI, were
      27.76 +/- 8.41, 0.17 +/- 0.05, and 1.29 +/- 0.76 cycles/degree, respectively. We
      found a significant negative correlation between subject age and MTF cutoff
      frequency (Pearson's correlation coefficient r = -0.606, p < 0.001), and between
      age and Strehl ratio (r = -0.649, p < 0.001). We also found a significant
      positive correlation between subject age and OSI (r = 0.691, p < 0.001).
      CONCLUSIONS: The MTF cutoff frequency and the Strehl ratio are significantly
      decreased, and the OSI is significantly increased, by aging, indicating that the
      optical quality of the eye is degraded in older subjects.

PMID- 22587341
TI  - A statistical analysis of the impact of advertising signs on road safety.
AB  - This research aims to investigate the impact of advertising signs on road safety.
      An exhaustive review of international literature was carried out on the effect of
      advertising signs on driver behaviour and safety. Moreover, a before-and-after
      statistical analysis with control groups was applied on several road sites with
      different characteristics in the Athens metropolitan area, in Greece, in order to
      investigate the correlation between the placement or removal of advertising signs
      and the related occurrence of road accidents. Road accident data for the 'before'
      and 'after' periods on the test sites and the control sites were extracted from
      the database of the Hellenic Statistical Authority, and the selected 'before' and
      'after' periods vary from 2.5 to 6 years. The statistical analysis shows no
      statistical correlation between road accidents and advertising signs in none of
      the nine sites examined, as the confidence intervals of the estimated safety
      effects are non-significant at 95% confidence level. This can be explained by the
      fact that, in the examined road sites, drivers are overloaded with information
      (traffic signs, directions signs, labels of shops, pedestrians and other
      vehicles, etc.) so that the additional information load from advertising signs
      may not further distract them.

PMID- 22587342
TI  - Oxidative DNA damage correlates with cell immortalization and mir-92 expression
      in hepatocellular carcinoma.
AB  - BACKGROUND: MicroRNAs expression has been extensively studied in hepatocellular
      carcinoma but little is known regarding the relationship, if any, with
      inflammation, production of reactive oxygen species (ROS), host's repair
      mechanisms and cell immortalization. This study aimed at assessing the extent of
      oxidative DNA damage (8-hydroxydeoxyguanosine - 8-OHdG) in different phases of
      the carcinogenetic process, in relation to DNA repair gene polymorphism,
      telomeric dysfunction and to the expression of several microRNAs, non-coding
      genes involved in post-transcriptional regulation, cell proliferation,
      differentiation and death. METHODS: Tissue samples obtained either at surgery,
      [neoplastic (HCC) and adjacent non-cancerous cirrhotic tissues (NCCT)] at
      percutaneous or laparoscopic biopsy (patients with HCV or HBV-related hepatitis
      or patients undergoing cholecystectomy) were analysed for 8-OHdG (HPLC-ED), OGG1
      (a DNA repair gene) polymorphism (PCR-RFLP), telomerase activity, telomere length
      (T/S, by RT-PCR), Taqman microRNA assay and Bad/Bax mRNA (RT-PCR). Fifty-eight
      samples from 29 HCC patients (obtained in both neoplastic and peritumoral
      tissues), 22 from chronic hepatitis (CH) and 10 controls (cholecystectomy
      patients - CON) were examined. RESULTS: Eight-OHdG levels were significantly
      higher in HCC and NCCT than in CH and CON (p=0.001). Telomerase activity was
      significantly higher in HCC than in the remaining subgroups (p=0.002); conversely
      T/S was significantly lower in HCC (p=0.05). MiR-199a-b, -195, -122, -92a and 
      145 were down-regulated in the majority of HCCs while miR-222 was up-regulated. A
      positive correlation was observed among 8-OHdG levels, disease stage, telomerase
      activity, OGG1 polymorphisms and ALT/GGT levels. In HCC, miR-92 expression
      correlated positively with telomerase activity, 8-OHdG levels and Bad/Bax mRNA.
      CONCLUSIONS: The above findings confirm the accumulation, in the progression of
      chronic liver damage to HCC, of a ROS-mediated oxidative DNA damage, and suggest
      that this correlates with induction of telomerase activity and, as a novel
      finding, with over-expression of miR-92, a microRNA that plays a role in both the
      apoptotic process and in cellular proliferation pathways.

PMID- 22587344
TI  - Outlier detection using projection quantile regression for mass spectrometry data
      with low replication.
AB  - BACKGROUND: Mass spectrometry (MS) data are often generated from various
      biological or chemical experiments and there may exist outlying observations,
      which are extreme due to technical reasons. The determination of outlying
      observations is important in the analysis of replicated MS data because elaborate
      pre-processing is essential for successful analysis with reliable results and
      manual outlier detection as one of pre-processing steps is time-consuming. The
      heterogeneity of variability and low replication are often obstacles to
      successful analysis, including outlier detection. Existing approaches, which
      assume constant variability, can generate many false positives (outliers) and/or
      false negatives (non-outliers). Thus, a more powerful and accurate approach is
      needed to account for the heterogeneity of variability and low replication.
      FINDINGS: We proposed an outlier detection algorithm using projection and
      quantile regression in MS data from multiple experiments. The performance of the
      algorithm and program was demonstrated by using both simulated and real-life
      data. The projection approach with linear, nonlinear, or nonparametric quantile
      regression was appropriate in heterogeneous high-throughput data with low
      replication. CONCLUSION: Various quantile regression approaches combined with
      projection were proposed for detecting outliers. The choice among linear,
      nonlinear, and nonparametric regressions is dependent on the degree of
      heterogeneity of the data. The proposed approach was illustrated with MS data
      with two or more replicates.

PMID- 22587343
TI  - Transmitted antiretroviral drug resistance and thumb subdomain polymorphisms
      among newly HIV type 1 diagnosed patients infected with CRF01_AE and CRF07_BC
      virus in Guangdong Province, China.
AB  - The aim of this study was to elucidate the prevalence of transmitted drug
      resistant (TDR) mutations and reverse transcriptase (RT) thumb subdomain
      polymorphisms in CRF01_AE and CRF07_BC virus among newly diagnosed, therapy-naive
      HIV-1 patients in Guangdong Province, China. One hundred and sixty-four samples
      were collected in the Guangzhou Eighth People's Hospital. The entire protease
      gene and 300 codons of the entry part of the reverse transcriptase were amplified
      and sequenced. Furthermore, genotypic drug resistance, polymorphisms, and their
      phylogeny were analyzed. According to eligibility criteria, seven samples were
      excluded, and 119 of 157 (75.8%) samples (84 CRF01_AE and 35 CRF07_BC) were
      amplified and sequenced successfully. The prevalence of TDR identified in the
      present study was 6.7% [8/119, 95% confidence interval (CI) 1.8-11.6%]. Three
      major resistance mutations, K103N, M184V, and Y188L, each of which caused more
      than one drug resistance, appeared in only two patients; the prevalence [1.7 %
      (2/119)] was relatively low. Until now, this is the first observation of the five
      newly identified accessory mutations, V35T, K43E, V60I, K122E, and E203D, and
      seven thumb subdomain polymorphisms, A272P, K277R, K281R, T286A, E291D, V292I,
      and I293V, in the RT gene in China. These findings provide useful information for
      guidance on the antiretroviral therapy (ART) policy in China where therapeutic
      options are still limited.

PMID- 22587348
TI  - Erratum.

PMID- 22587345
TI  - No pharmacokinetic interaction between ipragliflozin and sitagliptin,
      pioglitazone, or glimepiride in healthy subjects.
AB  - AIMS: To investigate the effect of ipragliflozin on the pharmacokinetics of
      sitagliptin, pioglitazone or glimepiride and vice versa in healthy subjects.
      METHODS: Three trials with an open-label, randomized, two-way crossover design
      were conducted in healthy subjects. Ipragliflozin 150 mg, sitagliptin 100 mg,
      pioglitazone 30 mg or glimepiride 1-2 mg were administered alone or in
      combination. Primary endpoints were the area under the curve from the time of
      dosing to infinity (AUC(inf)) and the maximum observed plasma concentration
      (C(max)) of each drug. RESULTS: Multiple doses of ipragliflozin did not change
      the AUC(inf) and C(max) of a single dose of sitagliptin, pioglitazone or
      glimepiride. All geometric mean ratios and 90% CIs for AUC(inf) and C(max) , with
      and without ipragliflozin, were within the predefined range of 80-125% (AUC(inf)
      : sitagliptin 100.1 [96.9-103.5], pioglitazone 101.7 [96.6-107.0], glimepiride
      105.1 [101.3-109.0], and C(max) : sitagliptin 92.4 [82.8-103.1], pioglitazone
      98.6 [87.7-110.8], glimepiride 110.0 [101.9-118.8]). Similarly, multiple doses of
      sitagliptin, pioglitazone or glimepiride did not change the pharmacokinetics of a
      single dose of ipragliflozin (AUC(inf) : 95.0 [93.4-103.1], 100.0 [98.1-102.0],
      99.1 [96.6-101.6]; and C(max) : 96.5 [90.4-103.1], 93.5 [86.3-101.2], 97.3 [89.2
      106.2]). Ipragliflozin either alone or in combination with any of the three
      glucose-lowering drugs was well tolerated in healthy subjects. CONCLUSION:
      Ipragliflozin did not affect the pharmacokinetics of sitagliptin, pioglitazone or
      glimepiride and vice versa, suggesting that no dose-adjustments are likely to be
      required when ipragliflozin is given in combination with other glucose-lowering
      drugs in patients with type 2 diabetes mellitus.

PMID- 22587350
TI  - Overexpression of serine hydroxymethyltransferase from halotolerant
      cyanobacterium in Escherichia coli results in increased accumulation of choline
      precursors and enhanced salinity tolerance.
AB  - Serine hydroxymethyltransferase (SHMT) is a key enzyme in cellular one-carbon
      pathway and has been studied in many living organisms from bacteria to higher
      plants and mammals. However, biochemical and molecular characterization of SHMT
      from photoautotrophic microorganisms remains a challenge. Here, we isolated the
      SHMT gene from a halotolerant cyanobacterium Aphanothece halophytica (ApSHMT) and
      expressed it in Escherichia coli. Purified recombinant ApSHMT protein exhibited
      catalytic reactions for dl-threo-3-phenylserine as well as for l-serine.
      Catalytic reaction for l-serine was strongly inhibited by NaCl, but not to that
      level with glycine betaine. Overexpression of ApSHMT in E. coli resulted in the
      increased accumulation of glycine and serine. Choline and glycine betaine levels
      were also significantly increased. Under high salinity, the growth rate of ApSHMT
      expressing cells was faster compared to its respective control. High salinity
      also strongly induced the transcript level of ApSHMT in A. halophytica. Our
      results indicate the importance of a novel pathway; salt-induced ApSHMT increased
      the level of glycine betaine via serine and choline and conferred the tolerance
      to salinity stress.

PMID- 22587351
TI  - Differential roles of breakfast only (one meal per day) and a bigger breakfast
      with a small dinner (two meals per day) in mice fed a high-fat diet with regard
      to induced obesity and lipid metabolism.
AB  - BACKGROUND: Recent studies on humans and rodents have suggested that the timing
      of food intake plays an important role in circadian regulation and metabolic
      health. Consumption of high-fat foods during the inactive period or at the end of
      the awake period results in weight gain and metabolic syndrome in rodents.
      However, the distinct effects of breakfast size and the breakfast/dinner size
      ratio on metabolic health have not yet been fully examined in mice. METHODS: We
      examined whether the parameters of metabolic syndrome were differentially
      affected in mice that consumed a large meal at the beginning of the awake period
      (breakfast; one meal group) and a relatively smaller meal at end of the awake
      period (dinner; two meals group). The mice of each group were provided equal food
      volume per day. RESULTS: Mice on one meal exhibited an increase in body weight
      gain, hyperinsulinemia, hyperleptinemia, and a decrease of gene expression
      associated with beta-oxidation in adipose tissue and liver compared with those on
      two meals. The circadian expression pattern of the Clock gene in mice on one meal
      was disturbed compared with those on two meals. CONCLUSIONS: In conclusion, a
      bigger breakfast with a smaller dinner (two meals per day) but not breakfast only
      (one meal per day) helps control body weight and fat accumulation in mice on a
      high-fat meals schedule. The findings of this study suggest that dietary
      recommendations for weight reduction and/or maintenance should include
      information on the timing and quantity of dietary intake.

PMID- 22587353
TI  - Evidence for the likely origin of homochirality in amino acids, sugars, and
      nucleosides on prebiotic Earth.

PMID- 22587354
TI  - ZINC: a free tool to discover chemistry for biology.
AB  - ZINC is a free public resource for ligand discovery. The database contains over
      twenty million commercially available molecules in biologically relevant
      representations that may be downloaded in popular ready-to-dock formats and
      subsets. The Web site also enables searches by structure, biological activity,
      physical property, vendor, catalog number, name, and CAS number. Small custom
      subsets may be created, edited, shared, docked, downloaded, and conveyed to a
      vendor for purchase. The database is maintained and curated for a high purchasing
      success rate and is freely available at zinc.docking.org.

PMID- 22587355
TI  - Diagnostic and prognostic impact of serum-soluble UL16-binding protein 2 in lung
      cancer patients.
AB  - UL16-binding protein 2 (ULBP2) is one of the ligands for NKG2D (NKG2DL). ULBP2
      expression is induced in transformed cells and is recognized by immune effector
      cells via the activating NKG2D immunoreceptor. Soluble forms of NKG2DL have been
      reported in the serum of patients with several types of cancer. The present study
      investigated the diagnostic and prognostic significance of serum-soluble ULBP2
      (sULBP2) in lung cancer patients. We used flow cytometry to evaluate the surface
      expression of NKG2DL by various lung cancer cells, while sULBP2 was measured
      using our original ELISA. In addition, the immunological effect of sULBP2 on
      peripheral blood mononuclear cells (PBMC) was examined by the (51) Cr release
      assay. We found that ULBP2 was highly expressed and that the sULBP2 level was
      elevated in supernatants of cultured non-small-cell lung cancer (NSCLC) cells as
      well as in the serum of NSCLC patients. ULBP2 levels were especially high in
      squamous cell carcinoma (SQ) patients. Clinical stage IIIB and IV NSCLC patients
      with a sULBP2 level >= 8.7 pg/mL showed significantly shorter survival than
      patients with sULBP2 <8.7 pg/mL. In multivariate analysis, a sULBP2 level >= 8.7
      pg/mL (hazard ratio [HR], 2.13; P = 0.038) and clinical stage IV (HR, 2.65; P =
      0.019) were independent determinants of a poor outcome. As a possible mechanism,
      we demonstrated that sULBP2 directly suppresses the cytolytic activity of PBMC.
      In conclusion, ULBP2 is the most significant NKG2DL for lung cancer, and sULBP2
      is useful in the diagnosis of SQ and as a prognostic indicator for patients with
      advanced NSCLC.

PMID- 22587356
TI  - Intersecting discourses on race and sexuality: compounded colonization among
      LGBTTQ American Indians/Alaska Natives.
AB  - This article examines discourses on race and sexuality in scientific literature
      during the late-nineteenth and early-twentieth centuries in context of U.S.
      settler colonialism. It uses a theoretical and methodological intersectional
      perspective to identify rhetorical strategies deployed in discursive
      representations salient to lesbian, gay, bisexual, transgender, Two-Spirit, and
      queer American Indians and Alaska Natives. These representations reflect a
      context of compounded colonization, a historical configuration of co-constituting
      discourses based on cultural and ideological assumptions that invidiously marked
      a social group with consequential, continued effects. Hence, language is a vector
      of power and a critical vehicle in the project of decolonization.

PMID- 22587357
TI  - Unmet mental health and substance abuse treatment needs of sexual minority
      elders.
AB  - In a survey exploring the reliability and validity of a screening tool, we
      explored the substance abuse and mental health issues among 371 elders; 74 were
      sexual minorities. Analyses by age group indicated that elders 55-64 years had
      significantly more problems with substance abuse, posttraumatic stress disorder
      (PTSD), depression, anxiety, and suicidal thoughts compared to those 65 and
      older. Bisexuals reported significantly greater problems with depression,
      anxiety, and suicidality than either heterosexual or lesbian or gay elders.
      Mental health and substance abuse treatment utilization was low among all elders
      with problems. Implications for assessment, access to care, and group-specific
      services delivery are discussed.

PMID- 22587358
TI  - Deconstructing the silences: gay social memory.
AB  - Adopting a Foucaultian perceptive, this article deconstructs the silences in the
      Singaporean gay community. The collective absences in homosexuals' social memory
      is not simply reflective of a fragmented community, but must be comprehended in
      relation to the role of the state and media in shaping particular discourses.

PMID- 22587359
TI  - Weight loss and related behavior changes among lesbians.
AB  - Overweight and obesity are known risk factors for several modifiable, if not
      preventable diseases. Growing evidence suggests that lesbians may have higher
      rates of obesity than other women. This study was designed to describe weight
      loss and behavior changes related to food choices and exercise habits among
      lesbians who participated in a predominantly lesbian, mainstream, commercial
      weight loss program. Behavioral changes were recorded in exercise, quality of
      food choices, and number of times dining out. Although there were several
      limitations based on sample size and heterogeneity, the impact of a lesbian
      supportive environment for behavior change was upheld.

PMID- 22587360
TI  - "It ain't all as bad as it may seem": young Black lesbians' responses to sexual
      prejudice.
AB  - This article explores the ways in which young, Black lesbians manage their sexual
      minority identity when experiencing sexual prejudice. Fourteen Black lesbians
      between the ages of 16 and 24 participated in semistructured interviews.
      Instances of sexual prejudice and the young women's responses were thematically
      analyzed using open and axial qualitative coding techniques. Results indicated
      that participants experienced sexual prejudice frequently and even within the
      lesbian community. Responses to sexual prejudice included: cognitive reframing of
      heterosexist messages, passing, gaining support from self-created gay families,
      and fighting back (physically and verbally) in the event of isolated instances of
      sexual prejudice. Analysis focuses on how gender identity relates to experiences
      of sexual prejudice and identity management strategies. Findings suggest that
      there are parallels between the management strategies of these women and young,
      Black gay and bisexual males and between these women and Black women who are
      coping with sexism and racism.

PMID- 22587361
TI  - Beyond a lesbian space? An investigation on the intergenerational discourse
      surrounding lesbian public social places in Amsterdam.
AB  - This article investigates intergenerational discourse on public lesbian social
      spaces within Amsterdam, Netherlands. The author seeks to address how lesbian
      women from different generations talk about lesbian social spaces in Amsterdam
      through anthropological ethnographic research and semistructured interviews with
      20 lesbian women who have or currently are attending these places. The author
      also addresses the gradual decline of lesbian specific spaces in the city and the
      current belief that lesbian women are beyond having a public social space that
      services only the lesbian community. The rise in popularity of mixed gay- and
      lesbian-friendly bars and girl circuit parties will be identified as a key area
      where generational tensions and discourse are being played out. Issues pertaining
      to generational disagreements over lesbian identity, visibility, and space will
      be addressed.

PMID- 22587362
TI  - Legal consciousness and LGBT research: the role of the law in the everyday lives
      of LGBT individuals.
AB  - The law occupies a prominent place in the everyday lives of lesbian, gay,
      bisexual, and transgender (LGBT) individuals, and the continuing regulation and
      policing of sexuality and gender weighs heavily on many people who identify as
      LGBT. Despite remarkable progress in the area of LGBT civil rights, LGBT
      individuals in the United States still lack formal equality and are denied many
      of the protections that are afforded other historically disadvantaged groups.
      These legal disabilities represent an ongoing source of minority stress and can
      produce a correspondingly high degree of legal consciousness within the LGBT
      community.

PMID- 22587364
TI  - Long term follow-up of health-related quality of life in young adults born very
      preterm or with a very low birth weight.
AB  - BACKGROUND: The purpose was, first, to evaluate changes in health-related quality
      of life (HRQL) in a cohort of very low birth weight (VLBW; <1500 g.) or very
      preterm (< 32 weeks of gestation) children between ages 14 and 19, and second, to
      identify correlates of HRQL at age 19. METHODS: HRQL was assessed using the
      Health Utilities Index Mark 3 (HUI3). In order to explore correlates of HRQL, we
      performed a hierarchical regression analysis. RESULTS: Surviving VLBW children (n
      = 959) from a 1983 Dutch nation-wide cohort were eligible; 630 participated both
      at age 14 and 19; 54 at age 19 only. The mean HRQL score decreased from 0.87 to
      0.86. The HRQL of 45% was stable, 25% were better and 30% were worse. A
      regression model showed internalizing problems were related most strongly to
      HRQL. CONCLUSIONS: In the transition from adolescence to young adulthood, HRQL in
      Dutch VLBW children was stable at the group level but varied at the individual
      level. HRQL was negatively associated with internalizing problems and also with
      physical handicaps. Long-term follow-up studies on the impact of VLBW on HRQL are
      all the more called for, given the growing number of vulnerable infants surviving
      the neonatal period.

PMID- 22587365
TI  - Correlation of fasting serum apolipoprotein B-48 with coronary artery disease
      prevalence.
AB  - BACKGROUND: Postprandial hyperlipidemia partially refers to the postprandial
      accumulation of chylomicrons and chylomicron remnants (CM-R). Many in vitro
      studies have shown that CM-R has highly atherogenic properties, but consensus is
      lacking on whether CM-R accumulation correlates with the development of
      atherosclerotic cardiovascular diseases. We investigated the correlation between
      CM-R accumulation and the prevalence of coronary artery disease (CAD). DESIGN:
      Subjects who received a coronary angiography and did not take any lipid-lowering
      drugs (n = 189) were enrolled. Subjects with coronary artery stenosis (>= 75%)
      were diagnosed as CAD. Biochemical markers for glucose and lipid metabolism
      including fasting apolipoprotein (apo) B-48 concentration were compared between
      CAD patients (n = 96) and age-, sex-, and body mass index (BMI)-matched non-CAD
      subjects without overt coronary stenosis (< 75%) (n = 67). We tried to determine
      which metabolic parameters were correlated with the prevalence of CAD by multiple
      logistic regression analysis, and whether or not the combination of high apo B-48
      and other coronary risk factors (high triglyceride, low HDL-C, high HbA1c or low
      adiponectin levels) increased the prevalence of CAD. RESULTS: Fasting serum apo B
      48 levels were significantly higher in CAD patients than in non-CAD subjects (3.9
      +/- 2.4 vs. 6.9 +/- 2.6 MUg/mL, P < 0.0001) and had the most significant
      correlation with the existence of CAD. The clustering of high fasting apo B-48
      levels (> 4.34 MUg/mL, the cut-off value) and other coronary risk factors were
      found to be associated with a stronger risk of CAD compared with single high
      fasting apo B-48 levels. CONCLUSION: Fasting serum apo B-48 levels significantly
      correlated with the prevalence of CAD.

PMID- 22587366
TI  - Mutational analysis of putative phosphate- and proton-binding sites in the
      Saccharomyces cerevisiae Pho84 phosphate:H(+) transceptor and its effect on
      signalling to the PKA and PHO pathways.
AB  - In Saccharomyces cerevisiae, the Pho84 phosphate transporter acts as the main
      provider of phosphate to the cell using a proton symport mechanism, but also
      mediates rapid activation of the PKA (protein kinase A) pathway. These two
      features led to recognition of Pho84 as a transceptor. Although the physiological
      role of Pho84 has been studied in depth, the mechanisms underlying the transport
      and sensor functions are unclear. To obtain more insight into the structure
      function relationships of Pho84, we have rationally designed and analysed site
      directed mutants. Using a three-dimensional model of Pho84 created on the basis
      of the GlpT permease, complemented with multiple sequence alignments, we selected
      Arg(168) and Lys(492), and Asp(178), Asp(358) and Glu(473) as residues
      potentially involved in phosphate or proton binding respectively, during
      transport. We found that Asp(358) (helix 7) and Lys(492) (helix 11) are critical
      for the transport function, and might be part of the putative substrate-binding
      pocket of Pho84. Moreover, we show that alleles mutated in the putative proton
      binding site Asp(358) are still capable of strongly activating PKA pathway
      targets, despite their severely reduced transport activity. This indicates that
      signalling does not require transport and suggests that mutagenesis of amino acid
      residues involved in binding of the co-transported ion may constitute a promising
      general approach to separate the transport and signalling functions in
      transceptors.

PMID- 22587368
TI  - Simulation study of pO2 distribution in induced tumour masses and normal tissues
      within a microcirculation environment.
AB  - The biological microenvironment is interrupted when tumour masses are introduced
      because of the strong competition for oxygen. During the period of avascular
      growth of tumours, capillaries that existed play a crucial role in supplying
      oxygen to both tumourous and healthy cells. Due to limitations of oxygen supply
      from capillaries, healthy cells have to compete for oxygen with tumourous cells.
      In this study, an improved Krogh's cylinder model which is more realistic than
      the previously reported assumption that oxygen is homogeneously distributed in a
      microenvironment, is proposed to describe the process of the oxygen diffusion
      from a capillary to its surrounding environment. The capillary wall permeability
      is also taken into account. The simulation study is conducted and the results
      show that when tumour masses are implanted at the upstream part of a capillary
      and followed by normal tissues, the whole normal tissues suffer from hypoxia. In
      contrast, when normal tissues are ahead of tumour masses, their pO2 is
      sufficient. In both situations, the pO2 in the whole normal tissues drops
      significantly due to the axial diffusion at the interface of normal tissues and
      tumourous cells. As the existence of the axial oxygen diffusion cannot supply the
      whole tumour masses, only these tumourous cells that are near the interface can
      be partially supplied, and have a small chance to survive.

PMID- 22587367
TI  - What is the efficiency of ATP signaling from erythrocytes to regulate
      distribution of O(2) supply within the microvasculature?
AB  - Erythrocytes appear to be ideal sensors for regulating microvascular O(2) supply
      as they release the potent vasodilator ATP in an O(2) saturation-dependent
      manner. Whether erythrocytes play a significant role in regulating O(2) supply in
      the complex environment of diffusional O(2) exchange among capillaries,
      arterioles, and venules, depends on the efficiency with which erythrocytes signal
      the vascular endothelium. If one assumes that the distribution of purinergic
      receptors is uniform throughout the microvasculature, then the most efficient
      site for signaling should occur in capillaries, where the erythrocyte membrane is
      in close proximity to the endothelium. ATP released from erythrocytes would
      diffuse a short distance to P(2y) receptors inducing an increase in blood flow,
      possibly the result of endothelial hyperpolarization. We hypothesize that this
      hyperpolarization varies across the capillary bed depending upon erythrocyte
      supply rate and the flux of O(2) from these erythrocytes to support O(2)
      metabolism. This would suggest that the capillary bed would be the most effective
      site for erythrocytes to communicate tissue oxygen needs. Electrically coupled
      endothelial cells conduct the integrated signal upstream where arterioles adjust
      vascular resistance, thus enabling ATP released from erythrocytes to regulate the
      magnitude and distribution of O(2) supply to individual capillary networks.

PMID- 22587369
TI  - Association between Thr21Met and Ser89Asn polymorphisms of the urotensin-II
      (UTS2) gene, diabetes mellitus, and diabetic retinopathy.
AB  - PURPOSE: To evaluate possible role of the UTS2 gene polymorphisms (Thr21Met and
      Ser89Asn) in the genetic susceptibility to diabetic retinopathy (DR) in a Turkish
      population. METHODS: Total number of 280 patients with DR (nonproliferative DR
      170 and proliferative DR 110), 291 nondiabetic healthy controls, and 113 diabetic
      controls (without DR) were included to this study. The detection of UTS2 gene
      polymorphisms was achieved with PCR-RFLP technique. The Discovery Studio 2.1
      program was used for molecular modeling analysis. RESULTS: Thr21Met (T21M) and
      Ser89Asn (S89N) polymorphisms of the UTS2 gene were associated with the risk of
      developing diabetes and DR. M21M genotype frequencies were high in PDR (8.9% in
      diabetic control vs. 54.6% in PDR, P = 0.0092) group. Increases in 21M allele
      frequency (52.7% in diabetic control vs. 76.4% in PDR, P < 0.0001) frequency in
      PDR group were detected. However, there were no changes in genotype and allele
      frequencies for T21M in NPDR group. There were decreases in the S89N genotype
      (23.9% in diabetic control vs. 13.5%) and 89N allele frequencies (11.9% in
      diabetic control vs. 6.8%) in NPDR group. However, S89S genotype (76.1% in
      diabetic control vs. 86.4%) and 89S allele frequencies (88.1% in diabetic control
      vs. 93.2%) were high in NPDR group. Three haplotypes (MN, MS and TS) were
      associated with NPDR patients (P < 0.001), but only MN (P < 0.001) and TS
      haplotypes (P = 0.018) were associated in PDR group. Molecular modeling analysis
      showed that these two polymorphisms changed the 3D structure of UTS2, and
      provided interactions with neighboring residues. CONCLUSION: The associations
      between Thr21Met and Ser89Asn polymorphisms in the UTS2 gene and DR strongly
      suggest that these SNPs may be an important a risk factor for the development of
      DR in Caucasians, and could be candidate markers for earlier diagnosis and
      targets for DR therapy.

PMID- 22587370
TI  - The prevalence of early repolarization in patients with noncompaction
      cardiomyopathy presenting with malignant ventricular arrhythmias.
AB  - Early Repolarization in Noncompaction Cardiomyopathy.  BACKGROUND: Early
      repolarization (ER) is associated with malignant ventricular arrhythmias,
      including ventricular fibrillation (VF) and sudden cardiac death (SCD). One
      possible mechanism is increased trabeculation with deep intramyocardial
      invagination, carrying the Purkinje system deeper into the myocardium resulting
      in delayed depolarization and inhomogenous repolarization. Noncompaction
      cardiomyopathy (NCCM) is a recently classified, primary cardiomyopathy with
      excessive trabeculations. In these patients ventricular arrhythmias, including
      sustained VT and VF, occur frequently. The aim of this study was to determine the
      prevalence of ER in NCCM patients, especially in those primarily presenting with
      malignant ventricular arrhythmias or SCD. METHODS: We analyzed prospective data
      from our NCCM registry including 84 patients, median age: 40 (3-79) years.
      RESULTS: Fourteen patients (17%) initially presented with sustained VT (n = 5) or
      VF (n = 9) and 70 (83%) with heart failure or else. After the exclusion of 20
      patients with the left bundle branch block, 25 (39%) NCCM patients had ER; 3 (6%)
      located in inferior leads, 14 (27%) in lateral leads, and 8 (15%) in both. None
      had ER in leads V1 to V3. In those presenting with VT/VF, 9/12 (75%) had ER (2 in
      inferior leads, 3 in lateral leads and 4 in both), versus 16/52 (31%) in the
      other patients (P = 0.02). If the NCCM population was dichotomized according to
      the presence or absence of ER, the long-term outcome for VT/VF appeared worse in
      the ER positive patients (P = 0.05). CONCLUSION: There is a high prevalence of ER
      in NCCM patients, especially in those who present with malignant ventricular
      arrhythmias. (J Cardiovasc Electrophysiol, Vol. 23, pp. 938-944, September 2012).

PMID- 22587372
TI  - CytoITMprobe: a network information flow plugin for Cytoscape.
AB  - BACKGROUND: Cytoscape is a well-developed flexible platform for visualization,
      integration and analysis of network data. Apart from the sophisticated graph
      layout and visualization routines, it hosts numerous user-developed plugins that
      significantly extend its core functionality. Earlier, we developed a network
      information flow framework and implemented it as a web application, called ITM
      Probe. Given a context consisting of one or more user-selected nodes, ITM Probe
      retrieves other network nodes most related to that context. It requires neither
      user restriction to subnetwork of interest nor additional and possibly noisy
      information. However, plugins for Cytoscape with these features do not yet exist.
      To provide the Cytoscape users the possibility of integrating ITM Probe into
      their workflows, we developed CytoITMprobe, a new Cytoscape plugin. FINDINGS:
      CytoITMprobe maintains all the desirable features of ITM Probe and adds
      additional flexibility not achievable through its web service version. It
      provides access to ITM Probe either through a web server or locally. The input,
      consisting of a Cytoscape network, together with the desired origins and/or
      destinations of information and a dissipation coefficient, is specified through a
      query form. The results are shown as a subnetwork of significant nodes and
      several summary tables. Users can control the composition and appearance of the
      subnetwork and interchange their ITM Probe results with other software tools
      through tab-delimited files. CONCLUSIONS: The main strength of CytoITMprobe is
      its flexibility. It allows the user to specify as input any Cytoscape network,
      rather than being restricted to the pre-compiled protein-protein interaction
      networks available through the ITM Probe web service. Users may supply their own
      edge weights and directionalities. Consequently, as opposed to ITM Probe web
      service, CytoITMprobe can be applied to many other domains of network-based
      research beyond protein-networks. It also enables seamless integration of ITM
      Probe results with other Cytoscape plugins having complementary functionality for
      data analysis.

PMID- 22587373
TI  - Nomograms to predict the pathological stage of clinically localized prostate
      cancer in Korean men: comparison with western predictive tools using decision
      curve analysis.
AB  - OBJECTIVES: To develop and evaluate nomograms to predict the pathological stage
      of clinically localized prostate cancer after radical prostatectomy in Korean
      men. METHODS: We reviewed the medical records of 2041 patients who had clinical
      stages T1c-T3a prostate cancer and were treated solely with radical prostatectomy
      at two hospitals. Logistic regressions were carried out to predict organ-confined
      disease, extraprostatic extension, seminal vesicle invasion, and lymph node
      metastasis using preoperative variables and resulting nomograms. Internal
      validations were assessed using the area under the receiver operating
      characteristic curve and calibration plot, and then external validations were
      carried out on 129 patients from another hospital. Head-to-head comparisons with
      2007 Partin tables and Cancer of the Prostate Risk Assessment score were carried
      out using the area under the curve and decision curve analysis. RESULTS: The
      significant predictors for organ-confined disease and extraprostatic extension
      were clinical stage, prostate-specific antigen, Gleason score and a percent
      positive core of biopsy. Significant predictors for seminal vesicle invasion were
      prostate-specific antigen, Gleason score and percent positive core, and those for
      lymph node metastasis were prostate-specific antigen and percent positive core.
      The area under the curve of established nomograms for organ-confined disease,
      extraprostatic extension, seminal vesicle invasion and lymph node metastasis were
      0.809, 0.804, 0.889 and 0.838, respectively. The nomograms were well calibrated
      and externally validated. These nomograms showed significantly higher accuracies
      and net benefits than two Western tools in Korean men. CONCLUSION: This is the
      first study to have developed and fully validated nomograms to predict the
      pathological stage of prostate cancer in an Asian population. These nomograms
      might be more accurate and useful for Korean men than other predictive models
      developed using Western populations.

PMID- 22587376
TI  - Fifth Conversation in the Discipline Biomolecular Stereodynamics State University
      of New York at Albony, June 02-06, 1987.

PMID- 22587371
TI  - A gp41-based heteroduplex mobility assay provides rapid and accurate assessment
      of intrasubtype epidemiological linkage in HIV type 1 heterosexual transmission
      Pairs.
AB  - A critical step in HIV-1 transmission studies is the rapid and accurate
      identification of epidemiologically linked transmission pairs. To date, this has
      been accomplished by comparison of polymerase chain reaction (PCR)-amplified
      nucleotide sequences from potential transmission pairs, which can be cost
      prohibitive for use in resource-limited settings. Here we describe a rapid, cost
      effective approach to determine transmission linkage based on the heteroduplex
      mobility assay (HMA), and validate this approach by comparison to nucleotide
      sequencing. A total of 102 HIV-1-infected Zambian and Rwandan couples, with known
      linkage, were analyzed by gp41-HMA. A 400-base pair fragment within the envelope
      gp41 region of the HIV proviral genome was PCR amplified and HMA was applied to
      both partners' amplicons separately (autologous) and as a mixture (heterologous).
      If the diversity between gp41 sequences was low (<5%), a homoduplex was observed
      upon gel electrophoresis and the transmission was characterized as having
      occurred between partners (linked). If a new heteroduplex formed, within the
      heterologous migration, the transmission was determined to be unlinked. Initial
      blind validation of gp-41 HMA demonstrated 90% concordance between HMA and
      sequencing with 100% concordance in the case of linked transmissions. Following
      validation, 25 newly infected partners in Kigali and 12 in Lusaka were evaluated
      prospectively using both HMA and nucleotide sequences. Concordant results were
      obtained in all but one case (97.3%). The gp41-HMA technique is a reliable and
      feasible tool to detect linked transmissions in the field. All identified
      unlinked results should be confirmed by sequence analyses.

PMID- 22587378
TI  - Dynamic properties of a dirt and a synthetic equine racetrack surface measured by
      a track-testing device.
AB  - REASONS FOR PERFORMING STUDY: Racetrack surface is a risk factor for Thoroughbred
      racehorse injury and death that can be engineered and managed. To investigate the
      relationship between surface and injury, the mechanical behaviour of dirt and
      synthetic track surfaces must be quantified. OBJECTIVES: To compare dynamic
      properties of a dirt and a synthetic surface in situ using a track-testing device
      designed to simulate equine hoof impact; and to determine the effects of impact
      velocity, impact angle and repeated impact on dynamic surface behaviour. METHODS:
      A track-testing device measured force and displacement during impact into a dirt
      and a synthetic surface at 3 impact velocities (1.91, 2.30, 2.63 m/s), 2 impact
      angles (0 degrees , 20 degrees  from vertical), and 2 consecutive impacts
      (initial, repeat). Surfaces were measured at 3 locations/day for 3 days. The
      effects of surface type, impact velocity, impact angle and impact number on
      dynamic surface properties were assessed using analysis of variance. RESULTS:
      Synthetic surface maximum forces, load rates and stiffnesses were 37-67% of dirt
      surface values. Surfaces were less stiff with lower impact velocities, angled
      impacts and initial impacts. The magnitude of differences between dirt and
      synthetic surfaces increased for repeat impacts and higher impact velocities.
      CONCLUSIONS: The synthetic surface was generally softer than the dirt surface.
      Greatly increased hardness for repeat impacts corroborates the importance of
      maintenance. Results at different impact velocities suggest that surface
      differences will persist at higher impact velocities. POTENTIAL RELEVANCE: For
      both surfaces it is clearly important to prevent horse exposure to precompacted
      surfaces, particularly during high-speed training when the surface has already
      been trampled. These data should be useful in coordinating racetrack surface
      management with racehorse training to prevent injuries.

PMID- 22587379
TI  - Atypical signatures of motor variability found in an individual with ASD.
AB  - We provide objective metrics of sequential movements and study a young adolescent
      with Autism Spectrum Disorders (ASD) in relation to novice typical controls (TC)
      as they learned to perform beginners' martial-arts routines. We studied segments
      staged to hit an opponent simultaneously performed with supplemental segments. In
      TC instructed changes in speed had profound differential effects on the intended
      vs. supplemental segments that were absent in the ASD case. Moreover, the
      frequency-distribution of velocity and acceleration maxima in TC was well fitted
      by a Gamma distribution but in the ASD case the fit was exponential yielding
      uncannily precise motions with atypically low-range of spatio-temporal
      variability.

PMID- 22587380
TI  - Retro-mode imaging and fundus autofluorescence with scanning laser ophthalmoscope
      of retinal dystrophies.
AB  - BACKGROUND: Retinal dystrophies display a considerably wide range of phenotypic
      variability, which can make diagnosis and clinical staging difficult. The aim of
      the study is to analyze the contribution of retro-mode imaging (RMI) and fundus
      autofluorescence (FAF) to the characterization of retinal dystrophies. METHODS:
      Eighteen consecutive patients affected by retinal dystrophies underwent a
      complete ophthalmological examination, including best corrected visual acuity
      with ETDRS charts, blue-light fundus autofluorescence, (BL-FAF), near-infrared
      fundus autofluorescence (NIR-FAF), and RMI. The primary outcome was the
      identification of abnormal patterns on RMI. The secondary outcome was the
      correlation with the findings on BL-FAF and NIR-FAF. RESULTS: Overall, the main
      feature of RMI is represented by a pseudo-3D pattern of all the lesions at the
      posterior pole. More specifically, any accumulation of material within the retina
      appears as an area of elevation of different shape and size, displaying irregular
      and darker borders. No precise correlations between RMI, BL-AF, and NIR-AF
      imaging was found. CONCLUSIONS: RMI and FAF appear to be useful tools for
      characterizing retinal dystrophies. Non-invasive diagnostic tools may yield
      additional information on the clinical setting and the monitoring of the
      patients.

PMID- 22587381
TI  - alpha-Glycosylation by D-glucosamine-derived donors: synthesis of heparosan and
      heparin analogues that interact with mycobacterial heparin-binding hemagglutinin.
AB  - Numerous biomolecules possess alpha-D-glucosamine as structural component.
      However, chemical glycosylations aimed at this backbone are usually not easily
      attained without generating the unwanted beta-isomer. We report herein a
      versatile approach in affording full alpha-stereoselectivity built upon a
      carefully selected set of orthogonal protecting groups on a D-glucosaminyl donor.
      The excellent stereoselectivity provided by the protecting group combination was
      found independent of leaving groups and activators. With the trichloroacetimidate
      as the optimum donor leaving group, core skeletons of glycosylphosphatidyl
      inositol anchors, heparosan, heparan sulfate, and heparin were efficiently
      assembled. The orthogonal protecting groups were successfully manipulated to
      further carry out the total syntheses of heparosan tri- and pentasaccharides and
      heparin di-, tetra-, hexa-, and octasaccharide analogues. Using the heparin
      analogues, heparin-binding hemagglutinin, a virulence factor of Mycobacterium
      tuberculosis, was found to bind at least six sugar units with the interaction
      notably being entropically driven.

PMID- 22587382
TI  - Short-term glucose variability in healthy volunteers is not associated with
      raised oxidative stress markers.
AB  - It is unknown whether glycaemic variability adds to the risk of microvascular
      complications of diabetes over and above the mean glucose value for a patient. We
      examined the effect of purposefully induced short-term glycaemic variability on
      oxidative stress markers. Eleven healthy subjects underwent three sequential
      glycaemic states; sustained hyperglycaemia, sustained euglycaemia and variable
      glycaemia, using glycaemic clamps for 3 h. Twenty-four hours urinary 8
      isoprostane-PGF2alpha was measured before and after each glycaemic state to
      assess oxidative stress. The median and interquartile range of the urinary 8-iso
      PGF2alpha in ng/24 h were (1373, 513), (996, 298) and (1227, 472) for the
      euglycaemic, hyperglycaemic and variable states, respectively. There was no
      significant difference in urinary isoprostanes between the three different
      states; mean ranks 20.9, 11.9 and 18.2 for the euglycaemic state, hyperglycaemic
      state and glycaemic variability state, respectively, p = 0.083. In conclusion, we
      did not see a significant increase in the urinary isoprostanes when glycaemic
      variability was induced under controlled conditions in healthy individuals.

PMID- 22587383
TI  - Novel regulatory therapies for prevention of Graft-versus-host disease.
AB  - Graft-versus-host disease is one of the major transplant-related complications in
      allogeneic hematopoietic stem cell transplantation. Continued efforts have been
      made to prevent the occurrence of severe graft-versus-host disease by eliminating
      or suppressing donor-derived effector T cells. Conventional immunosuppression
      does not adequately prevent graft-versus-host disease, especially in mismatched
      transplants. Unfortunately, elimination of donor-derived T cells impairs stem
      cell engraftment, and delays immunologic reconstitution, rendering the recipient
      susceptible to post-transplant infections and disease relapse, with potentially
      lethal consequences. In this review, we discuss the role of dynamic immune
      regulation in controlling graft-versus-host disease, and how cell-based therapies
      are being developed using regulatory T cells and other tolerogenic cells for the
      prevention and treatment of graft-versus-host disease. In addition, advances in
      the design of cytoreductive conditioning regimens to selectively target graft
      versus-host disease-inducing donor-derived T cells that have improved the safety
      of allogeneic stem cell transplantation are reviewed. Finally, we discuss
      advances in our understanding of the tolerogenic facilitating cell population, a
      phenotypically and functionally distinct population of bone marrow-derived cells
      which promote hematopoietic stem cell engraftment while reducing the risk of
      graft-versus-host disease.

PMID- 22587384
TI  - Computational studies of darunavir into HIV-1 protease and DMPC bilayer:
      necessary conditions for effective binding and the role of the flaps.
AB  - Human immunodeficiency virus type 1 protease (HIV-1 PR) is one of the main
      targets toward AIDS therapy. We have selected the potent drug darunavir and a
      weak inhibitor (fullerene analog) as HIV-1 PR substrates to compare protease's
      conformational features upon binding. Molecular dynamics (MD), molecular
      mechanics Poisson-Boltzmann surface area (MM-PBSA), and quantum-mechanical (QM)
      calculations indicated the importance of the stability of HIV-1 PR flaps toward
      effective binding: a weak inhibitor may induce flexibility to the flaps, which
      convert between closed and semiopen states. A water molecule in the darunavir-HIV
      1 PR complex bridged the two flap tips of the protease through hydrogen bonding
      (HB) interactions in a stable structure, a feature that was not observed for the
      fullerene-HIV-1 PR complex. Additionally, despite that van der Waals interactions
      and nonpolar contribution to solvation favored permanent fullerene entrapment
      into the cavity, these interactions alone were not sufficient for effective
      binding; enhanced electrostatic interactions as observed in the darunavir-complex
      were the crucial component of the binding energy. An alternative pathway to the
      usual way of a ligand to access the cavity was also observed for both compounds.
      Each ligand entered the binding cavity through an opening between the one flap of
      the protease and a neighboring loop. This suggested that access to the cavity is
      not necessarily regulated by flap opening. Darunavir exerts its biological action
      inside the cell, after crossing the membrane barrier. Thus, we also initiated a
      study on the interactions between darunavir and the DMPC bilayer to reveal that
      the drug was accommodated inside the bilayer in conformations that resembled its
      structure into HIV-1 PR, being stabilized via HBs with the lipids and water
      molecules.

PMID- 22587386
TI  - Abstracts of the XXV International Symposium on Technological Innovations in
      Laboratory Hematology. May 21-24, 2012. Nice, France.

PMID- 22587385
TI  - The economic burden of pleural effusions in patients with chronic myeloid
      leukemia treated with tyrosine kinase inhibitors.
AB  - OBJECTIVE: Tyrosine kinase inhibitors (TKI), the standard of care for patients
      with chronic myeloid leukemia (CML) patients, may in some cases lead to the
      development of pleural effusion (PE). The purpose of this study is to compare
      healthcare resource utilization and costs associated with PE among CML patients
      treated with a TKI therapy. METHODS: Two large retrospective claims databases
      (1999-2009) were combined to identify adult CML patients who received >=1 TKI
      prescription before the index date, which was defined as 30 days before the first
      PE diagnosis for patients with PE and a randomly selected date for PE-free
      patients. Patients were followed for 6 months after the index date. PE and PE
      free patients were matched on a 1:1 ratio. PE-related resource utilization and
      costs (measured in 2009 US dollars) were estimated for PE patients. All-cause and
      CML-related resource utilization and costs were compared between PE and PE-free
      patients. Multivariate regression models were used to control for confounding
      factors. RESULTS: The study included 186 matched pairs. PE-free and PE patients
      were on average 65.4 and 63.6 years old and 39.8% and 48.9% were female,
      respectively. PE patients had a significantly higher number of inpatient (IP)
      days, IP admissions, outpatient (OP) visits and emergency room (ER) visits than
      PE-free patients (all p < 0.01). All-cause medical services costs were $88,526
      and $30,434 for PE and PE-free patients, respectively. After adjusting for
      confounding factors, the PE-related total medical costs were $47,288 (p < 0.01),
      which was mostly accounted for by higher IP (difference: $34,123, p < 0.01) and
      OP (difference: $9563, p < 0.05) costs. PE patients also incurred higher CML
      related medical costs compared to PE-free patients (difference: $39,599; p <
      0.01). CONCLUSION: PE presents a substantial economic burden for CML patients
      treated with TKI.

PMID- 22587245
TI  - Observation of a new chi(b) state in radiative transitions to Upsilon(1S) and
      Upsilon(2S) at ATLAS.
AB  - The chi(b)(nP) quarkonium states are produced in proton-proton collisions at the
      Large Hadron Collider at sqrt[s] = 7  TeV and recorded by the ATLAS detector.
      Using a data sample corresponding to an integrated luminosity of 4.4  fb(-1),
      these states are reconstructed through their radiative decays to Upsilon(1S,2S)
      with Upsilon -> MU+ MU-. In addition to the mass peaks corresponding to the decay
      modes chi(b)(1P,2P) -> Upsilon(1S)gamma, a new structure centered at a mass of
      10.530 +/- 0.005(stat) +/- 0.009(syst)  GeV is also observed, in both the
      Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This structure is interpreted
      as the chi(b)(3P) system.

PMID- 22587387
TI  - Oral health-related quality of life in an aging Canadian population.
AB  - BACKGROUND: The purpose of the study is to describe the impact of oral health
      related quality of life (OHRQoL) on the lives of pre-seniors and seniors living
      in Nova Scotia, Canada. METHODS: This cross-sectional study involved 1461
      participants, grouped by age (pre-seniors [45-64] and seniors [65+]) and
      residential status (long-term care facility [LTC] or community). OHRQoL was
      measured using the 14-item Oral Health Impact Profile questionnaire (OHIP-14) in
      a random digit dialing telephone survey (for community residents) or a face-to
      face interview (for LTC residents). Intra-oral examinations were performed by one
      of six dentists calibrated to W.H.O. standards. RESULTS: Approximately one in
      four pre-seniors and seniors reported at least one OHRQoL impact 'fairly/very
      often'. The most commonly reported impacts were within the dimensions 'physical
      pain' and 'psychological discomfort'. It was found that 12.2% of LTC residents
      found it uncomfortable to eat any foods 'fairly/very' often compared to 7.7% in
      the community, and 11.6% of LTC residents reported being self-conscious
      'fairly/very often' compared to 8.2% in the community. Of those residing in the
      community, pre-seniors (28.8%) reported significantly more impacts than seniors
      (22.0%); but there were no significant differences in OHRQoL between pre-seniors
      (21.2%) and seniors (25.3%) in LTC. Pre-seniors living in the community scored
      significantly higher than community dwelling seniors on prevalence, extent and
      severity of OHIP-14 scores. Logistic regression revealed that for the community
      dwelling sample, individuals living in rural areas in addition to those being
      born outside of Canada were approximately 2.0 times more likely to report an
      impact 'fairly/very often', whereas among the LTC sample, those having a high
      school education or less were 2.3 times more likely to report an impact.
      CONCLUSIONS: Findings indicate that the oral health and OHRQoL of both pre
      seniors and seniors in LTC residents is poor. Community dwelling pre-seniors have
      the highest prevalence rate of oral impacts.

PMID- 22587388
TI  - SIL index, comprising stage, soluble interleukin-2 receptor, and lactate
      dehydrogenase, is a useful prognostic predictor in diffuse large B-cell lymphoma.
AB  - Rituximab (R) plus doxorubicin, cyclophosphamide, vincristine, and prednisolone
      (CHOP) chemotherapy (R-CHOP) is widely accepted as standard care for diffuse
      large B-cell lymphoma (DLBCL) patients. The revised International Prognostic
      Index (R-IPI) was established in 2007 after the addition of rituximab to standard
      DLBCL treatment. To reassess the utility of R-IPI, we carried out a retrospective
      analysis of patients with DLBCL uniformly treated with standard R-CHOP.
      Progression-free survival (PFS) curves in "very good" and "good" risk groups as
      defined by the R-IPI showed no statistical difference. We added soluble
      interleukin-2 receptor (sIL-2R) level to the factors comprising the R-IPI. Five
      levels of sIL-2R were weighed with respect to their impact on PFS. sIL-2R of
      >2500 U/mL was determined as the most appropriate threshold. We developed a new
      prognostic SIL index, which includes three independent prognostic risk factors:
      clinical stage (S); sIL-2R level over 2500 U/mL (I); and elevated lactate
      dehydrogenase level (L). This index indicates standard risk (0 or 1 risk factors,
      4-year PFS 83%, 4-year overall survival 91%) and high risk (2 or 3 risk factors,
      4-year PFS 52%, 4-year overall survival 67%) outcomes. The SIL index is a simple
      and objective prognostic index for DLBCL patients to identify candidates for
      experimental therapy other than R-CHOP.

PMID- 22587390
TI  - Influence of a postural change of the swimmer's head in hydrodynamic performances
      using 3D CFD.
AB  - This study deals with recent researches undertaken by the authors in the field of
      hydrodynamics of human swimming. The aim of this numerical study was to
      investigate the flow around the entire swimmer's body. The results presented in
      this article focus on the combination of a 3D computational fluid dynamics code
      and the use of the k-omega turbulence model, in the range of Reynolds numbers
      representative of a swimming level varying from national to international
      competition. Emphasis is placed on the influence of a postural change of the
      swimmer's head in hydrodynamic performances, which is directly related to the
      reduction of overall drag. These results confirm and complete those, less
      accurate, of a preliminary 2D study recently published by the authors and allow
      the authors to optimise the swimmer's head position in underwater swimming.

PMID- 22587392
TI  - Solid organ transplant recipients presenting for Mohs micrographic surgery: a
      retrospective case-control study.
AB  - BACKGROUND: Solid organ transplant recipients (SOTR) have a high risk of
      cutaneous malignancy. Mohs micrographic surgery (MMS) is recommended for the
      treatment of skin cancers in this group. The characteristics of the tumors in
      SOTR presenting for MMS are not well documented. OBJECTIVE: To describe the
      characteristics of tumors in SOTR presenting to a single institution over an 11
      year period and compare them with tumors of non-SOTR who have also undergone MMS.
      METHODS: A database query captured patients with a current organ transplant who
      underwent MMS. These patients (cases) were matched to controls who also underwent
      MMS. Statistical models were used to identify tumor and operative characteristics
      significantly associated with SOTR compared with matching controls. RESULTS:
      Ninety-two SOTR underwent MMS for 432 skin cancers; 163 controls had 269 skin
      cancers. Squamous cell carcinoma (SCC) was the most common tumor in SOTR, with a
      reversal of the usual ratio of basal cell carcinoma to SCC. Mean tumor and defect
      sizes were similar in SOTR and controls. Cardiac transplants were the predominant
      transplant. CONCLUSIONS: SOTR referred for MMS have disproportionately more and
      different types of skin cancers than controls.

PMID- 22587393
TI  - Direct observation of ligand rebinding pathways in hemoglobin using femtosecond
      mid-IR spectroscopy.
AB  - The dynamics of NO rebinding in hemoglobin (Hb) was directly observed using
      femtosecond mid-IR spectroscopy after photodeligation of NO from HbNO in D(2)O at
      283 K. Time-resolved spectra of bound NO appeared to have a single feature peaked
      at 1616 cm(-1) but were much better described by two Gaussians with equal
      intensities but different rebinding kinetics, where the feature at 1617 cm(-1)
      rebinds faster than the one at 1614 cm(-1). It is possible that the two bands
      each correspond to one of two subunit constituents of the tetrameric Hb.
      Transient absorption spectra of photodeligated NO revealed three evolving bands
      near 1858 cm(-1) and their red-shifted replicas. The red-shifted replicas arise
      from photodeligated NO in the vibrationally excited v = 1 state. More than 10% of
      the NO was dissociated into the vibrationally excited v = 1 state when photolyzed
      by a 580 nm pulse. The three absorption bands for the deligated NO could be
      attributed to three NO sites in or near the heme pocket. The kinetics of the
      three transient bands for the deligated NO, as well as the recovery of the bound
      NO population, was most consistent with a kinetics scheme that incorporates time
      dependent rebinding from one site that rapidly equilibrates with the other two
      sites. The time dependence results from a time-dependent rebinding barrier due to
      conformational relaxation of protein after deligation. By assigning each
      absorption band to a site in the heme pocket of Hb, a pathway for rebinding of NO
      to Hb was proposed.

PMID- 22587391
TI  - p130Cas-dependent actin remodelling regulates myogenic differentiation.
AB  - Actin dynamics are implicated in various cellular processes, not only through the
      regulation of cytoskeletal organization, but also via the control of gene
      expression. In the present study we show that the Src family kinase substrate
      p130Cas (Cas is Crk-associated substrate) influences actin remodelling and
      concomitant muscle-specific gene expression, thereby regulating myogenic
      differentiation. In C2C12 myoblasts, silencing of p130Cas expression by RNA
      interference impaired F-actin (filamentous actin) formation and nuclear
      localization of the SRF (serum-response factor) co-activator MAL (megakaryocytic
      acute leukaemia) following the induction of myogenic differentiation.
      Consequently, formation of multinucleated myotubes was abolished. Re-introduction
      of wild-type p130Cas, but not its phosphorylation-defective mutant, into p130Cas
      knockdown myoblasts restored F-actin assembly, MAL nuclear localization and
      myotube formation. Depletion of the adhesion molecule integrin beta3, a key
      regulator of myogenic differentiation as well as actin cytoskeletal organization,
      attenuated p130Cas phosphorylation and MAL nuclear localization during C2C12
      differentiation. Moreover, knockdown of p130Cas led to the activation of the F
      actin-severing protein cofilin. The introduction of a dominant-negative mutant of
      cofilin into p130Cas-knockdown myoblasts restored muscle-specific gene expression
      and myotube formation. The results of the present study suggest that p130Cas
      phosphorylation, mediated by integrin beta3, facilitates cofilin inactivation and
      promotes myogenic differentiation through modulating actin cytoskeleton
      remodelling.

PMID- 22587394
TI  - Precision of ocular response analyzer.
AB  - PURPOSE: To evaluate the repeatability of corneal hysteresis (CH) and corneal
      resistance measurements as well as the consistency of the four shots within each
      measurement using the ocular response analyzer (ORA, Reichert Ophthalmic
      Instruments, Depew, NY) and to generate a pool of data of a normal population.
      METHODS: A total of 45 eyes from 45 healthy volunteers without ocular pathologies
      and normal visual acuity were enrolled in this study. A sequence of five
      consecutive measurements was performed with each patient with the ORA. The
      biomechanical properties of the cornea in terms of CH and corneal resistance
      factor (CRF) were recorded, as well as the Goldmann-correlated IOP (IOPg) and
      cornea correlated IOP (IOPcc). The trend in each measurement sequence was
      analyzed and Cronbach's alpha was derived for the repeatability. The average of
      four shots within each measurement was compared with the best signal value (BSV)
      provided by the internal data processing of the ORA. RESULTS: Mean value for CH
      was 11.58 and BSV was 11.55. For CRF, mean value was 11.21 and BSV was 11.28. No
      significant difference was found between the average value and the BSV of one
      measurement (p > 0.05). No significant difference was found between the average
      value and the BSV of the five consecutive measurements, only IOPg showed a
      significant difference (p = 0.017), average value of IOPg is higher than BSV.
      Within a sequence of five measurements for each individual, the average values of
      the four shots per measurement for IOPg and IOPcc are decreasing by 1.19 and 1.05
      mmHg on average. The repeatability test revealed good results for CH and CRF (all
      alpha are higher than 0.9). CONCLUSION: The ORA provides, beside intraocular
      pressure additional, information about the biomechanical properties of the cornea
      such as hysteresis and resistance. It proves to yield good repeatability for
      corneal hysteresis and resistance in normal subjects.

PMID- 22587389
TI  - Haem oxygenase 1 expression is altered in monocytes from patients with systemic
      lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by
      multiple functional alterations affecting immune cells, such as B cells, T cells,
      dendritic cells (DCs) and monocytes. During SLE, the immunogenicity of monocytes
      and DCs is significantly up-regulated, promoting the activation of self-reactive
      T cells. Accordingly, it is important to understand the contribution of these
      cells to the pathogenesis of SLE and the mechanisms responsible for their altered
      functionality during disease. One of the key enzymes that control monocyte and DC
      function is haem oxygenase-1 (HO-1), which catalyses the degradation of the haem
      group into biliverdin, carbon monoxide and free iron. These products possess
      immunosuppressive and anti-inflammatory capacities. The main goal of this work
      was to determine HO-1 expression in monocytes and DCs from patients with SLE and
      healthy controls. Hence, peripheral blood mononuclear cells were obtained from 43
      patients with SLE and 30 healthy controls. CD14(+) monocytes and CD4(+) T cells
      were sorted by FACS and HO-1 expression was measured by RT-PCR. In addition, HO-1
      protein expression was determined by FACS. HO-1 levels in monocytes were
      significantly reduced in patients with SLE compared with healthy controls. These
      results were confirmed by flow cytometry. No differences were observed in other
      cell types, such as DCs or CD4(+) T cells, although decreased MHC-II levels were
      observed in DCs from patients with SLE. In conclusion, we found a significant
      decrease in HO-1 expression, specifically in monocytes from patients with SLE,
      suggesting that an imbalance of monocyte function could be partly the result of a
      decrease in HO-1 expression.

PMID- 22587395
TI  - Community structure of methanogenic archaea and methane production associated
      with compost-treated tropical rice-field soil.
AB  - The diversity and density of methanogenic archaea and methane production were
      investigated ex situ at different growth stages of rice plant cultivated in
      compost-treated tropical rice fields. The qPCR analysis revealed variation in
      methanogens population from 3.40 * 10(6)  to 1.11 * 10(7)  copies g(-1)  dws, in
      the year 2009 and 4.37 * 10(6)  to 1.36 * 10(7)  copies g(-1)  dws in the year
      2010. Apart from methanogens, a large number of bacterial (9.60 * 10(9) -1.44 *
      10(10)  copies g(-1)  dws) and archaeal (7.13 * 10(7) -3.02 * 10(8)  copies g(-1)
      dws) communities were also associated with methanogenesis. Methanogen population
      size varied in the order: flowering > ripening > tillering > postharvest >
      preplantation stage. The RFLP-based 16S rRNA gene-targeted phylogenetic analysis
      showed that clones were closely related to diverse group of methanogens
      comprising members of Methanomicrobiaceae, Methanosarcinaceae, Methanosaetaceae
      and RC I. Laboratory incubation studies revealed higher amount of cumulative
      CH(4)  at the flowering stage. The integration of methanogenic community
      structure and CH(4)  production potential of soil resulted in a better
      understanding of the dynamics of CH(4)  production in organically treated rice
      field soil. The hypothesis that the stages of plant development influence the
      methanogenic community structure leading to temporal variation in the CH(4) 
      production has been successfully tested.

PMID- 22587396
TI  - Redox cycling of 1,2-naphthoquinone by thioredoxin1 through Cys32 and Cys35
      causes inhibition of its catalytic activity and activation of ASK1/p38 signaling.
AB  - 1,2-Naphthoquinone (1,2-NQ) is an atmospheric chemical capable of (1) redox
      cycling with electron donors and (2) covalent modification of nucleophilic groups
      on proteins. In the present study, we investigated its interaction with the redox
      protein, thioredoxin1 (Trx1), which led to oxidative stress-dependent cell
      damage. In experiments with purified wild-type Trx1 and its double mutant
      (32S/35S Trx1), we found that incubation of Trx1 with 1,2-NQ resulted in a redox
      cycling reaction, generating superoxide and hydrogen peroxide involving Cys32 and
      Cys35 and an arylation reaction resulting in covalent modification of Lys85
      together with a loss of Trx activity. A significant fraction of the lost Trx1
      activity following interaction with 1,2-NQ was restored by dithiothreitol.
      Exposure of RAW264.7 cells to 1,2-NQ generated reactive oxygen species (ROS) and
      caused a decrease in Trx activity. Trx is a negative regulator of apoptosis
      signal-regulating kinase 1 (ASK1), and under the conditions of the experiment,
      1,2-NQ activated ASK1 and p38, leading to PARP cleavage and apoptotic cell death
      that were blocked by pretreatment with polyethylene glycol-catalase. These
      results suggest that Trx1 readily undergoes oxidative modification by 1,2-NQ
      through the proximal thiols Cys32 and Cys35. It seems likely that ROS production
      concomitant with decline in cellular Trx activity plays a role in the activation
      of ASK1/p38 signaling to promote apoptotic cell death cause by 1,2-NQ exposure.

PMID- 22587397
TI  - New three-dimensional head-mounted display system, TMDU-S-3D system, for
      minimally invasive surgery application: procedures for gasless single-port
      radical nephrectomy.
AB  - We present an application of a new three-dimensional head-mounted display system
      that combines a high-definition three-dimensional organic electroluminescent head
      mounted display with a high-definition three-dimensional endoscope to minimally
      invasive surgery, using gasless single-port radical nephrectomy procedures as a
      model. This system presents the surgeon with a higher quality of magnified three
      dimensional imagery in front of the eyes regardless of head position, and
      simultaneously allows direct vision by moving the angle of sight downward. It is
      also significantly less expensive than the current robotic surgery system. While
      carrying out gasless single-port radical nephrectomy, the system provided the
      surgeon with excellent three-dimensional imagery of the operative field, direct
      vision of the outside and inside of the patient, and depth perception and tactile
      feedback through the devices. All four nephrectomies were safely completed within
      the operative time, blood loss was within usual limits and there were no
      complications. The display was light enough to comfortably be worn for a long
      operative time. Our experiences show that the three-dimensional head-mounted
      display system might facilitate maneuverability and safety in minimally invasive
      procedures, without prohibitive cost, and thus might mitigate the drawbacks of
      other three-dimensional vision systems. Because of the potential benefits that
      this system offers, it deserves further refinements of its role in various
      minimally invasive surgeries.

PMID- 22587398
TI  - Tungsten-enhanced growth of Methanosphaera stadtmanae.
AB  - BACKGROUND: The methanogenic Archaea Methanosphaera stadtmanae has been detected
      in the human gut microbiota by both culture and culture-independent methods. Its
      growth reaches an exponential phase after 5 to 7-day culture in medium 322 (10%
      vol). Our recent successful isolation of Methanomassiliicoccus luminyensis, a
      tungstate-selenite-requiring Archaea sharing similar metabolism characteristics
      with M. stadtmanae prompted us to study the effects of tungsten and selenium on
      M. stadtmanae growth. FINDINGS: Addition of 0.2 mg/L sodium tungstate to medium
      322 yielded, 48 hours after inoculation, a growth rate equivalent to that
      obtained after 6 days with control culture as measured by methane monitoring and
      optical density measurement. Addition of 50 MUg/mL sodium selenate had no effect
      on M. stadtmanae growth. Quantitative real-time PCRs targeting the M. stadtmanae
      16S rRNA confirmed these data. CONCLUSIONS: These data provide new information
      regarding the poorly known nutritional requirements of the human gut colonizing
      organismsM. stadtmanae. Adding sodium tungstate to basal medium may facilitate
      phenotypic characterization of this organism and additionally aid the isolation
      of new Archaea from complex host microbiota.

PMID- 22587399
TI  - Tachycardia-induced tachycardia.

PMID- 22587402
TI  - Upcoming New Feature in the Journal of Biomolecular Structure & Dynamics.

PMID- 22587404
TI  - Fasting, Ramadan and diabetes.

PMID- 22587405
TI  - Ramadan Prospective Diabetes Study: the role of drug dosage and timing
      alteration, active glucose monitoring and patient education.
AB  - AIMS: To observe the effects of active glucose monitoring, alteration of drug
      dosage and timing, dietary counselling and patient education in the occurrence of
      acute diabetic complications in fasting individuals with diabetes during the
      month of Ramadan. METHODS: This prospective study was conducted at the outpatient
      department of the Baqai Institute of Diabetology and Endocrinology. Two
      educational sessions, one about drug dosage and timing alteration and glucose
      monitoring, and the other about dietary and lifestyle modifications, were given
      to the patients by a doctor and a dietician, respectively. Patients who had been
      recruited were advised to note their blood glucose readings on a chart for at
      least 15 fasting days, twice a day with at least one reading in the fasting
      state. RESULTS: A total of 3946 readings were obtained in 110 subjects; 82
      readings were in the hypoglycaemic range, and there were 22 episodes of
      symptomatic hypoglycaemia and 60 episodes of biochemical hypoglycaemia observed
      in 27 patients. Seven patients experienced symptomatic hypoglycaemia, whereas 20
      patients had biochemical hypoglycaemia. Symptomatic hypoglycaemic episodes showed
      a downward trend from weeks 1 to 4. The highest frequencies of hypo- and
      hyperglycaemic episodes were observed pre-dawn. None of the patients developed
      diabetic ketoacidosis or hyperglycaemic hyperosmolar state. CONCLUSION: We
      observed that, with active glucose monitoring, alteration of drug dosage and
      timing, dietary counselling and patient education, the majority of the patients
      did not have any serious acute complications of diabetes during Ramadan.

PMID- 22587406
TI  - Self-monitoring of blood glucose in Type 2 diabetes: cross-sectional analyses in
      1993, 1999 and 2009.
AB  - AIM: To characterize the numbers of reagent strips dispensed for self-monitoring
      of blood glucose to patients with Type 2 diabetes in Tayside, Scotland, in 1993,
      1999 and 2009. METHODS: A diabetes clinical information system in Tayside, record
      linked to electronic dispensed prescribing records, was used to collate all
      dispensed prescribing records for three cross-sectional samples of patients with
      Type 2 diabetes in 1993 (n = 5728), 1999 (n = 8109) and at 1 January 2009 (n =
      16,450). The numbers of reagent strips dispensed during the relevant calendar
      year were calculated and patients stratified by treatment. We also explored
      whether age, sex or material and social deprivation were associated with whether
      a patient received strips. RESULTS: Proportions of people who received self
      monitoring reagent strips increased from 15.5% in 1993, to 24.2% in 1999 to 29.8%
      in 2009, as did numbers of strips dispensed. While the proportion of diet-treated
      patients who received reagent strips was still very low in 2009 (5.6%), the
      proportion among those treated with oral agents tripled from 9.4 to 27.4% between
      1993 and 2009. Over 90% of patients treated with insulin received reagent strips
      and, among non-insulin-treated patients, this was more common among women,
      younger people and less deprived groups. CONCLUSIONS: The numbers of reagent
      strips dispensed for self-monitoring of blood glucose has increased and almost
      all insulin-treated patients receive strips. While few diet-treated patients
      receive strips, they are more extensively dispensed to those treated with oral
      agents. Given that self-monitoring of blood glucose is no longer routinely
      recommended in non-insulin treated patients, strategies to reduce unnecessary
      dispensing of reagent strips are needed.

PMID- 22587408
TI  - Recurrence of the acute Charcot foot in diabetes.
AB  - BACKGROUND: The acute Charcot foot is thought to occur in people who have a
      number of predisposing factors, of which distal neuropathy is the most important.
      But while occurrence in the contralateral foot is not infrequent, recurrence in
      the same foot seems to be very rare. CASE REPORT: A case is described in which
      discrete episodes of inflammation of the midfoot occurred in the same foot over a
      period of 14 years, and were attributed to acute Charcot neuroarthropathy
      (Charcot foot). There was coincidental evidence of osteomyelitis of the 4(th) toe
      but there was no suspicion that the inflammatory episodes of the midfoot were the
      result of bone infection and they settled without treatment with antibiotics.
      CONCLUSION: This case had clinically diagnosed recurrences of inflammation and
      destruction typical of the acute Charcot foot over an extended period, and this
      is most unusual. The implications of the rarity of such recurrences are
      discussed.

PMID- 22587407
TI  - Trait anxiety and glucose metabolism in people without diabetes: vulnerabilities
      among black women.
AB  - AIMS: We examined whether the relationship between anxiety and indicators of
      glucose metabolism in people without diabetes varies by race and gender. METHODS:
      Participants were 914 adults (777 white, 137 black) without diabetes in the MIDUS
      (Midlife in the USA) II study. Glucose metabolism was characterized by fasting
      glucose, insulin, HOMA-IR (homeostasis model of assessment--insulin resistance),
      and HbA(1c). Hierarchical linear regressions stratified by race and gender
      examined whether anxiety was associated with glucose metabolism. RESULTS: After
      adjustment for potential confounders, positive relationships between anxiety and
      fasting glucose (P = 0.04), insulin (P = 0.01), and HOMA-IR (P = 0.02) but not
      HbA(1c), were observed in black women only. CONCLUSIONS: Our findings extend
      previous evidence for the links between psychosocial vulnerabilities and impaired
      glucose metabolism in black women, by documenting significant associations
      between anxiety and clinical indicators of glycaemic control among black women
      without diabetes. Thus, anxiety might constitute an intervention target in black
      women, a subgroup disproportionately affected by Type 2 diabetes, its
      complications, and premature mortality.

PMID- 22587409
TI  - Exceptionally long-lived luminescence from [Cu(I)(isocyanide)2(phen)]+ complexes
      in nanoporous crystals enables remarkable oxygen gas sensing.
AB  - We report crystalline mixed-ligand copper complexes with phenanthroline and
      isocyanides with almost millesecond emission lifetimes that are efficient
      dioxygen sensors. The oxygen sensitivity of the prototype ([Cu(CN
      xylyl)(2)(dmp)]tfpb, dmp = 2,9-dimethyl-1,10-phenanthroline; CN-xylyl = 2,6
      dimethylphenylisocyanide; tfpb = tetrakis(bis-3,5-trifluoromethylphenylborate) is
      38 times better than that of [Ru(phen)(3)]tfpb(2) (phen = 1,10-phenanthroline).

PMID- 22587411
TI  - Validation of the Neurological Fatigue Index for stroke (NFI-Stroke).
AB  - BACKGROUND: Fatigue is a common symptom in Stroke. Several self-report scales are
      available to measure this debilitating symptom but concern has been expressed
      about their construct validity. OBJECTIVE: To examine the reliability and
      validity of a recently developed scale for multiple sclerosis (MS) fatigue, the
      Neurological Fatigue Index (NFI-MS), in a sample of stroke patients. METHOD: Six
      patients with stroke participated in qualitative interviews which were analysed
      and the themes compared for equivalence to those derived from existing data on MS
      fatigue. 999 questionnaire packs were sent to those with a stroke within the past
      four years. Data from the four subscales, and the Summary scale of the NFI-MS
      were fitted to the Rasch measurement model. RESULTS: Themes identified by stroke
      patients were consistent with those identified by those with MS. 282
      questionnaires were returned and respondents had a mean age of 67.3 years; 62%
      were male, and were on average 17.2 (SD 11.4, range 2-50) months post stroke. The
      Physical, Cognitive and Summary scales all showed good fit to the model, were
      unidimensional, and free of differential item functioning by age, sex and time.
      The sleep scales failed to show adequate fit in their current format. CONCLUSION:
      Post stroke fatigue appears to be represented by a combination of physical and
      cognitive components, confirmed by both qualitative and quantitative processes.
      The NFI-Stroke, comprising a Physical and Cognitive subscale, and a 10-item
      Summary scale, meets the strictest measurement requirements. Fit to the Rasch
      model allows conversion of ordinal raw scores to a linear metric.

PMID- 22587412
TI  - Two unique recombinant forms identified in incident HIV type 1 infections in Thai
      blood donors.
AB  - HIV-1 genetic diversity of recently seroconverting (<12 months) Thai repeated
      blood donors attending the National Blood Centre, Thai Red Cross Society (NBC,
      TRCS) from September 2007 until March 2008 was assessed. Ten HIV-1 recent
      seroconvertors (10/239,134 donations) were identified during the study period.
      The estimated median time to seroconversion was 67.3 days (range: 45.5-102.0
      days), and viral load ranged from 307 to 341,805 copies HIV-1 RNA/ml. MHAbce, a
      real-time-based PCR genotyping assay, identified six CRF01_AE, two CRF01_AE/B
      recombinants, one subtype B, and one CRF01_AE/B dual infection. Nine samples were
      further characterized by full genome sequencing, identifying CRF01_AE (N=6),
      unique CRF01_AE/B recombinants (N=2), and subtype B (N=1). One recombinant
      contained 13 breakpoints located in gag, pol, vif, vpr, env, and nef while the
      other recombinant contained 10 breakpoints located in pol, vif, env, and nef.
      This study found two unique CRF01B recombinants circulating in 10 recent HIV-1
      positive subjects from a blood donor population in Thailand.

PMID- 22587410
TI  - Bariatric surgery and T2DM improvement mechanisms: a mathematical model.
AB  - BACKGROUND: Consensus exists that several bariatric surgery procedures produce a
      rapid improvement of glucose homeostasis in obese diabetic patients, improvement
      apparently uncorrelated with the degree of eventual weight loss after surgery.
      Several hypotheses have been suggested to account for these results: among these,
      the anti-incretin, the ghrelin and the lower-intestinal dumping hypotheses have
      been discussed in the literature. Since no clear-cut experimental results are so
      far available to confirm or disprove any of these hypotheses, in the present work
      a mathematical model of the glucose-insulin-incretin system has been built,
      capable of expressing these three postulated mechanisms. The model has been
      populated with critically evaluated parameter values from the literature, and
      simulations under the three scenarios have been compared. RESULTS: The modeling
      results seem to indicate that the suppression of ghrelin release is unlikely to
      determine major changes in short-term glucose control. The possible existence of
      an anti-incretin hormone would be supported if an experimental increase of GIP
      concentrations were evident post-surgery. Given that, on the contrary, collected
      evidence suggests that GIP concentrations decrease post-surgery, the lower
      intestinal dumping hypothesis would seem to describe the mechanism most likely to
      produce the observed normalization of Type 2 Diabetes Mellitus (T2DM) after
      bariatric surgery. CONCLUSIONS: The proposed model can help discriminate among
      competing hypotheses in a context where definitive data are not available and
      mechanisms are still not clear.

PMID- 22587413
TI  - Guided tissue regeneration using rigid absorbable membranes in the dog model of
      chronic furcation defect.
AB  - OBJECTIVE: Absorbable membranes are used to promote the regeneration of
      periodontal defects by Guided Tissue Regeneration (GTR). However, their collapse
      into the defect is commonly reported, impairing regeneration. Therefore,
      absorbable but rigid membranes aiming at preventing such collapse were developed
      and analyzed in periodontal regeneration. MATERIALS AND METHODS: Membranes were
      analyzed in class II furcation defects in dogs; procedures included periodontal
      disease induction, prophylaxis and GTR (treated groups) or open flap debridement
      alone (control group). For GTR, the membranes were made of either 25%
      hydroxyapatite (HA) in polyhydroxybutyrate matrix (PHB) or 35% HA in PHB. Animals
      were clinically evaluated for gingival recession, clinical attachment level (CAL)
      and biopsies were collected at 60 and 120 days. Bone volume, trabeculae number,
      trabecular thickness and trabecular separation were quantified by micro-computed
      tomography, followed by histology. RESULTS: Membrane exposure was observed in
      both treated groups (25 and 35% HAP) from the 8(th) day after surgery,
      continuously progressing until 120 days. Mean CAL for all groups remained above
      normal values for dogs. Bone volumetric values were not significantly different.
      Partial formation of bone, cementum and periodontal ligament was observed in
      treated groups. An inflammatory infiltrate was observed in the dense connective
      tissue that partially filled the center of the treated defects with active
      osteoclasts on bone surface. CONCLUSION: Although partial regeneration of the
      defect was observed, it was limited by wound contamination. Consequently, rigid
      absorbable membranes made of HA and PHB failed to improve the regeneration of
      class II furcation defects in dogs.

PMID- 22587414
TI  - Influence of altered gait patterns on the hip joint contact forces.
AB  - Children who exhibit gait deviations often present a range of bone deformities,
      particularly at the proximal femur. Altered gait may affect bone growth and lead
      to deformities by exerting abnormal stresses on the developing bones. The
      objective of this study was to calculate variations in the hip joint contact
      forces with different gait patterns. Muscle and hip joint contact forces of four
      children with different walking characteristics were calculated using an inverse
      dynamic analysis and a static optimisation algorithm. Kinematic and kinetic
      analyses were based on a generic musculoskeletal model scaled down to accommodate
      the dimensions of each child. Results showed that for all the children with
      altered gaits both the orientation and magnitude of the hip joint contact force
      deviated from normal. The child with the most severe gait deviations had hip
      joint contact forces 30% greater than normal, most likely due to the increase in
      muscle forces required to sustain his crouched stance. Determining how altered
      gait affects joint loading may help in planning treatment strategies to preserve
      correct loading on the bone from a young age.

PMID- 22587415
TI  - Longitudinal Evaluation of Transition Services ("LETS Study"): protocol for
      outcome evaluation.
AB  - BACKGROUND: Because of advances in medical treatment, most children with physical
      disabilities can expect to achieve near normal life spans. Typically, coordinated
      teams of health care providers in specialized pediatric settings care for these
      children. As these children reach adulthood, however, the availability of
      services and expertise changes because the adult health care system has different
      processes designed to meet their specialized needs. Gaps in continuity of care
      during the transition from pediatric to adult services, and associated poor
      health outcomes are well documented. In response, new models of care are being
      introduced to address the complex process of health care transition. This paper
      describes a study protocol of a client-centred, prospective, longitudinal, mixed
      method evaluation of linked model of health care across the lifespan (the
      LIFEspan Model), offered by a pediatric rehabilitation centre and an adult
      rehabilitation centre. METHOD: This project will include a process and an outcome
      evaluation of the LIFEspan Model. The process evaluation will detail the specific
      service delivery that occurs with respect to preparation for transition and
      transfer of care through chart audits of pediatric medical records and
      qualitative interviews with LIFEspan staff. The outcome evaluation will measure
      the effect of the model on: 1) maintaining continuity within the health care
      system from pediatric to adult care; and 2) secondary outcomes related to health,
      well-being, social participation, transition readiness, and health care
      utilization of youth with cerebral palsy and acquired brain injury. Standardized
      instruments will include Health Utilities Inventory, Assessment of Life Habits,
      Arc's Self-Determination, Assessment of Health-Related Quality of Life, Partners
      in Health Questionnaire, Social Support Questionnaire, and Self-Efficacy for
      Managing Chronic Disease. DISCUSSION: The LETS study will be original in its
      undertaking of a prospective examination of outcomes 1-year post-transition, use
      of multiple comparison groups, and absence of disability-related exclusion
      criteria ensuring that the transition experiences of varied populations of young
      people and their families will be represented. TRIAL REGISTRATION:
      http://www.clinicaltrials.gov, ID NCT00975338.

PMID- 22587416
TI  - Aurora-A activation, correlated with hypoxia-inducible factor-1alpha, promotes
      radiochemoresistance and predicts poor outcome for nasopharyngeal carcinoma.
AB  - Previously, we and others showed that hypoxia-inducible factor-1alpha (HIF
      1alpha) and transcriptionally upregulated Aurora-A were required for disease
      progression in several tumors. Here, we address the clinicopathologic value of
      Aurora-A and HIF-1alpha in locally advanced nasopharyngeal carcinoma (NPC).
      Aurora-A and HIF-1alpha expression was semiquantitatively evaluated by
      immunohistochemistry staining in 144 cases from a randomized controlled trial. Of
      these patients, 69 received neoadjuvant chemotherapy plus concurrent
      chemoradiotherapy, and acted as the training set, and 75 cases treated with
      neoadjuvant chemotherapy plus radiotherapy were used as the testing set to
      validate the prognostic effect of Aurora-A and HIF-1alpha. We found that Aurora-A
      and HIF-1alpha were highly expressed in NPC, but were deficient in normal
      adjacent epithelia. In the testing set, Aurora-A overexpression predicted a
      shortened 5-year overall survival (59.1% vs 82.5%, P = 0.024), progression-free
      survival (44.8% vs 79.8%, P = 0.004), and distant metastasis-free survival (43.0%
      vs 17.3%, P = 0.016). Multivariate regression analysis confirmed that Aurora-A
      was indeed an independent prognostic factor for death, recurrence, and distant
      metastasis both in the testing set and overall patients. Moreover, a positive
      correlation between Aurora-A and HIF-1alpha was detected (P = 0.037).
      Importantly, although HIF-1alpha did not show any prognostic effect for patient
      outcome, the subset with Aurora-A and HIF-1alpha co-overexpression had the
      poorest overall, progression-free, and distant metastasis-free survival (all P <
      0.05). Our results confirmed that Aurora-A was an independent prognostic factor
      for NPC. Aurora-A combined with HIF-1alpha refined the risk definition of the
      patient subset, thus potentially directing locally advanced NPC patients for more
      selective therapy.

PMID- 22587417
TI  - Treating scars: addressing surface, volume, and movement to optimize results:
      part 1. Mild grades of scarring.
AB  - BACKGROUND: The management of scarring (from acne, surgery, or disease) remains a
      common concern and an ongoing challenge, with improvement, not eradication, the
      goal. METHODS: To describe a growing strategy used in esthetic dermatology
      illustrating the effects of movement, volume, and surface changes on skin aging,
      deformity, or disease using a grading scale of disease burden to classify scarred
      patients. RESULTS: Through the use of this grading scale and with emphasis on the
      role of surface, volume changes, and recurrent movement, treatment planning will
      be suggested and relevant treatments reviewed. Tabulated treatment planning will
      also present algorithms summarizing a logical approach to the treatment of more
      minor grades of scarring. CONCLUSION: More-minor grades of scarring may be
      assessed in terms of treatments to restore minor volume loss and to improve the
      surface of the skin.

PMID- 22587418
TI  - Editorial: The developmental psychopathologist as scientist-sleuth--can large
      scale longitudinal birth cohort studies provide the missing clues?

PMID- 22587419
TI  - A key structural domain of the Candida albicans Mdr1 protein.
AB  - A major multidrug transporter, MDR1 (multidrug resistance 1), a member of the MFS
      (major facilitator superfamily), invariably contributes to an increased efflux of
      commonly used azoles and thus corroborates their direct involvement in MDR in
      Candida albicans. The Mdr1 protein has two transmembrane domains, each comprising
      six transmembrane helices, interconnected with extracellular loops and ICLs
      (intracellular loops). The introduction of deletions and insertions through
      mutagenesis was used to address the role of the largest interdomain ICL3 of the
      MDR1 protein. Most of the progressive deletants, when overexpressed, eliminated
      the drug resistance. Notably, restoration of the length of the ICL3 by
      insertional mutagenesis did not restore the functionality of the protein.
      Interestingly, most of the insertion and deletion variants of ICL3 became
      amenable to trypsinization, yielding peptide fragments. The homology model of the
      Mdr1 protein showed that the molecular surface-charge distribution was perturbed
      in most of the ICL3 mutant variants. Taken together, these results provide the
      first evidence that the CCL (central cytoplasmic loop) of the fungal MFS
      transporter of the DHA1 (drug/proton antiporter) family is critical for the
      function of MDR. Unlike other homologous proteins, ICL3 has no apparent role in
      imparting substrate specificity or in the recruitment of the transporter protein.

PMID- 22587420
TI  - Knowledge and practices of pig farmers regarding Japanese encephalitis in
      Kathmandu, Nepal.
AB  - Japanese encephalitis (JE) is the single largest cause of viral encephalitis in
      the world and has been endemic in Nepal since the early 1980s. Since then, it has
      spread from its origins in lowland plains to the Kathmandu Valley as well as in
      hill and mountain districts. Pigs are amplifying hosts for the virus. The Nepal
      government has been encouraging the development of pig farming as a means of
      poverty alleviation. Whereas other countries have reduced JE through vaccination
      programmes and improvements in pig husbandry, these options are not economically
      possible in Nepal. The objective of this study was to examine the occupational
      risk of pig farmers in Nepal and to determine their level of knowledge and
      practice of JE prevention techniques. We surveyed 100 randomly selected pig
      farmers in the Kathmandu District and found that pig farmers were exposed to many
      JE risk factors including poverty and close proximity to pigs, rice paddy fields
      and water birds, which are the definitive hosts for the virus. Forty-two percent
      of the farmers had heard of JE, 20% associated it with mosquito bites and 7%
      named pigs as risk factors. Few protective measures were taken. None of the
      farmers were vaccinated against JE nor were any pigs, despite an ongoing human
      vaccination campaign. This farming community had little ownership of land and
      limited education. JE education programmes must consider gender differences in
      access to public health information as there were an equal number of male and
      female farmers. We provide findings that can inform future JE education
      programmes for this vulnerable population.

PMID- 22587421
TI  - Water model tuning for improved reproduction of rotational diffusion and NMR
      spectral density.
AB  - A water model for molecular simulation was optimized to improve the reproduction
      of translational and rotational diffusion of pure water and proteins. The
      SPC/E(b) model was developed from the original SPC/E model with a slight increase
      of the O-H bond length of 1%. This tuning has significantly improved the
      translational and rotational diffusion when compared to the experimental values,
      whereas only small changes were observed in the other thermodynamic properties
      examined. The overall tumbling correlation times (tau(p)) from ubiquitin, protein
      G, bovine pancreatic trypsin inhibitor, and barstar C42/80A were successfully
      reproduced using the SPC/E(b) model. Calculated site-specific spectral densities
      of the main chain amide bond rotation in ubiquitin and protein G were in good
      agreement with those derived from nuclear magnetic resonance reduced spectral
      density mapping. The SPC/E(bT) model was also developed with temperature
      dependent bond-length tuning to facilitate reproduction of the experimental
      tau(p) around room temperature.

PMID- 22587422
TI  - Pharmacokinetics of dasatinib for Philadelphia-positive acute lymphocytic
      leukemia with acquired T315I mutation.
AB  - BACKGROUND: The BCR-ABL T315I kinase domain mutation is insensitive to dasatinib
      therapy for Philadelphia-positive acute lymphoid leukemia (Ph + ALL) patients.
      Resistant T315I clone may be present prior to initiating dasatinib, which could
      expand under selective pressures during treatment. However, it is also possible
      that Ph + ALL patients newly acquire the T315I mutation during dasatinib therapy.
      Despite the potent inhibition of BCR-ABL kinase by dasatinib, little is known
      about the relationship between dasatinib pharmacokinetics and the emergence of
      kinase domain mutations in vivo. METHODS: To determine whether plasma dasatinib
      pharmacokinetics influences the emergence of BCR-ABL mutations, we measured
      plasma dasatinib levels in 11 Ph + ALL patients undergoing dasatinib monotherapy.
      RESULTS: Bone marrow relapse occurred in 5 of the 11 Ph + ALL patients (45%).
      Importantly, a T315I mutation was detected in 4 of the 5 relapsed patients,
      despite the absence of BCR-ABL mutations in any patient at baseline. The median
      plasma concentration at 2 hours (C(2h)), the median plasma maximum concentration
      (C(max)), and the median area under the observed plasma concentration-time curve
      from 0 to 4 hours (AUC(0-4)) were all significantly lower in patients with T315I
      than those without the mutation (C(2h), 22.3 ng/mL vs. 111.6 ng/mL, P = 0.0242;
      C(max), 43.8 ng/mL vs. 112.4 ng/mL, P = 0.0242; AUC(0-4), 108.3 ng.h/mL vs. 268.3
      ng.h/mL, P = 0.0061, respectively). CONCLUSIONS: These data indicate that the
      emergence of the T315I mutation among Ph + ALL patients treated with dasatinib
      is, in part, dependent on plasma dasatinib pharmacokinetics. Notably, these data
      also suggest that newly acquired BCR-ABL mutations may be inhibited by an
      increased exposure of dasatinib.

PMID- 22587423
TI  - Left atrial appendage occlusion by the WATCHMAN device: a beneficial procedure?

PMID- 22587424
TI  - Development of insulin allergy after bone marrow transplantation.
AB  - BACKGROUND: Insulin allergy is a not uncommon condition even though human insulin
      and insulin analogues are widely used. However, the development of insulin
      allergy after bone marrow transplantation has not been reported. CASE REPORT: A
      44-year-old Japanese woman had aplastic anaemia and secondary haemochromatosis.
      She was diagnosed with having diabetes at age 32 years and had been treated with
      human insulin. At age 34 years, bone marrow transplantation was performed. One
      year later, a rash and urticaria appeared immediately after insulin injections.
      Intracutaneous tests were positive for both human insulins and analogues, whereas
      the test for protamine was negative. Furthermore, an IgE-radioallergosorbent test
      against insulin was positive. Thus, we diagnosed the patient with having an IgE
      mediated type I allergy against insulin. Insulin therapy with insulin aspart,
      which showed the least skin reaction, was continued and the insulin allergy
      disappeared in 7 years. CONCLUSIONS: This is the first description of insulin
      allergy after bone marrow transplantation. Our case underscores the effects of
      bone marrow cells on IgE-mediated type I allergy for insulin.

PMID- 22587425
TI  - Standard abdominal wound edge protection with surgical dressings vs coverage with
      a sterile circular polyethylene drape for prevention of surgical site infections
      (BaFO): study protocol for a randomized controlled trial.
AB  - BACKGROUND: Postoperative surgical site infections cause substantial morbidity,
      prolonged hospitalization, costs and even mortality and remain one of the most
      frequent surgical complications. Approximately 14% to 30% of all patients
      undergoing elective open abdominal surgery are affected and methods to reduce
      surgical site infection rates warrant further investigation and evaluation in
      randomized controlled trials. METHODS/DESIGN: To investigate whether the
      application of a circular plastic wound protector reduces the rate of surgical
      site infections in general and visceral surgical patients that undergo midline or
      transverse laparotomy by 50%. BaFO is a randomized, controlled, patient-blinded
      and observer-blinded multicenter clinical trial with two parallel surgical
      groups. The primary outcome measure will be the rate of surgical site infections
      within 45 days postoperative assessed according to the definition of the Center
      for Disease Control. Statistical analysis of the primary endpoint will be based
      on the intention-to-treat population. The global level of significance is set at
      5% (2 sided) and sample size (n = 258 per group) is determined to assure a power
      of 80% with a planned interim analysis for the primary endpoint after the
      inclusion of 340 patients. DISCUSSION: The BaFO trial will explore if the rate of
      surgical site infections can be reduced by a single, simple, inexpensive
      intervention in patients undergoing open elective abdominal surgery. Its
      pragmatic design guarantees high external validity and clinical relevance.

PMID- 22587431
TI  - Can graphene oxide cause damage to eyesight?
AB  - As graphene becomes one of the most exciting candidates for multifunctional
      biomedical applications, contact between eyes and graphene-based materials is
      inevitable. On the other hand, eyes, as a special organ in the human body, have
      unique advantages to be used for testing new biomedical research and development,
      such as drug delivery. Intraocular biocompatible studies on graphene-related
      materials are thus essential. Here, we report our recent studies on intraocular
      biocompatibility and cytotoxicity of graphene oxide (GO) both in vitro and in
      vivo. The successful preparation of GO nanosheets was confirmed using atomic
      force microscopy, contact angle analyzer, Fourier transform infrared
      spectroscopy, and Raman spectroscopy. The influence of GO on human retinal
      pigment epithelium (RPE) cells in terms of the cell morphology, viability,
      membrane integrity, and apoptosis was investigated using various techniques,
      including optical micrography, cell counting kit-8 (CCK-8) assay, lactate
      dehydrogenase (LDH) assay, and apoptosis assay. The addition of GO had little
      influence on cell morphology, but the change was visible after long-time
      culturing. RPE cells showed higher than 60% cell viability by CCK-8 assay in GO
      solutions and less than 8% LDH release, although a small amount of apoptosis
      (1.5%) was observed. In vitro results suggested good biocompatibility of GO to
      RPE cells with slight adverse influence, on the cell viability and morphology in
      long-time periods, along with aggregation of GO. Thus, some further studies are
      needed to clarify the cytotoxicity mechanism of GO. GO intravitreally injected
      eyes showed few changes in eyeball appearance, intraocular pressure (IOP),
      eyesight, and histological photos. Our results suggested that GO did not cause
      any significant toxicity to the cell growth and proliferation. Intravitreal
      injection of GO into rabbits' eyes did not lead to much change in the eyeball
      appearance, IOP, electroretinogram, and histological examination.

PMID- 22587432
TI  - Hand hygiene instruction decreases illness-related absenteeism in elementary
      schools: a prospective cohort study.
AB  - BACKGROUND: Illness-related absences have been shown to lead to negative
      educational and economic outcomes. Both hand washing and hand sanitizer
      interventions have been shown to be effective in reducing illness-related
      absences. However, while the importance of hand hygiene in schools is clear, the
      role of instruction in use is less obvious. The purpose of this study was to
      compare absenteeism rates among elementary students given access to hand hygiene
      facilities versus students given both access and short repetitive instruction in
      use, particularly during influenza season when illness-related absences are at a
      peak. METHODS: A hand hygiene intervention was implemented from October to May
      during the 2009/2010 academic year, including peak flu season, in two Chicago
      Public Elementary Schools among students grades pre-kindergarten to eighth grade
      (ages 4-14). Classrooms were systematically assigned to an intervention or
      control group by grade (cluster design). Hand hygiene facilities (sanitizer and
      soap) were made available to all students. Students in the intervention group
      also received short repetitive instruction in hand hygiene every 2 months. Only
      absences as a result of respiratory or gastrointestinal illness were used to
      establish illness-related absenteeism rates. Percent absent days were calculated
      and bivariate analyses were performed to compare percent absent days among
      students given access to hand hygiene facilities versus students given both
      access and instruction. Prior to the intervention, teachers' perceptions of
      students' hand hygiene were also evaluated. Teacher perceptions were analysed to
      describe attitudes and beliefs. RESULTS: Data were collected and analysed for 773
      students reporting 1,886 absences during the study period (1.73% of total school
      days). Both the percent total absent days and percent illness-related absent days
      were significantly lower in the group receiving short instruction during flu
      season (P = 0.002, P < 0.001, respectively). This difference peaked during the
      influenza season (when intervention began) and declined in the following months.
      Teachers (n = 23) agreed that hand hygiene is not performed properly among
      students and reported time constraints as a barrier to frequent hand washing.
      CONCLUSIONS: Adding hand hygiene instruction to existing hand hygiene practices
      improved attendance at public elementary schools during the flu season.
      Standardized and brief repetitive instruction in hand hygiene holds potential to
      significantly reduce absenteeism.

PMID- 22587433
TI  - Prostatic relaxation induced by agmatine is decreased in spontaneously
      hypertensive rats.
AB  - What's known on the subject? and What does the study add? Neurotransmitters are
      known to control prostate contractility. Agmatine is one of them and induces
      relaxation through imidazoline receptors. The paper shows that the action of
      agmatine is reduced in hypertensive rats, and that this change is related to the
      decrease of ATP-sensitive potassium channels in the prostate. The findings can
      increase our understanding of the possible underlying mechanism for the
      development of clinical benign prostatic hyperplasia. OBJECTIVES: To compare
      agmatine-induced prostatic relaxation in hypertensive and control rats. To
      investigate the responsible mechanism(s) and the role of the ATP-sensitive
      potassium channel. METHODS: Prostate strips were isolated from male spontaneously
      hypertensive (SH) rats and normal Wistar-Kyoto (WKY) rats for measurement of
      isometric tension. The strips were precontracted with 1 umol/L phenylephrine or
      50 mmol/L KCl. Dose-dependent relaxation of the prostatic strips was studied by
      cumulative administration of agmatine, 1 to 100 umol/L, into the organ bath.
      Effects of specific antagonists on agmatine-induced relaxation were studied.
      Western blotting analysis was used to measure the gene expression of the ATP
      sensitive potassium channel in the rat prostate. RESULTS: Prostatic relaxation
      induced by agmatine was markedly reduced in SH rats compared with WKY rats. The
      relaxation caused by agmatine was abolished by BU224, a selective imidazoline
      I(2)-receptor antagonist, but was not modified by efaroxan at a dose sufficient
      to block imidazoline I(1)-receptors. The relaxation induced by diazoxide at a
      concentration sufficient to activate ATP-sensitive potassium channels was
      markedly reduced in the SH rat prostate. Expressions of ATP-sensitive potassium
      channel sulphonylurea receptor and inwardly rectifying potassium channel (Kir)
      6.2 subunits were both decreased in the prostate of SH rats. CONCLUSION: The
      decrease of agmatine-induced prostatic relaxation in SH rats is related to the
      change in ATP-sensitive potassium channels.

PMID- 22587434
TI  - On high-cycle fatigue of 316L stents.
AB  - This paper deals with fatigue life prediction of 316L stainless steel cardiac
      stents. Stents are biomedical devices used to reopen narrowed vessels. Fatigue
      life is dominated by the cyclic loading due to the systolic and diastolic
      pressure and the design against premature mechanical failure is of extreme
      importance. Here, a life assessment approach based on the Dang Van high cycle
      fatigue criterion and on finite element analysis is applied to explore the
      fatigue reliability of 316L stents subjected to multiaxial fatigue loading. A
      finite element analysis of the stent vessel subjected to cyclic pressure is
      performed to carry out fluctuating stresses and strain at some critical elements
      of the stent where cracks or complete fracture may occur. The obtained results
      show that the loading path of the analysed stent subjected to a pulsatile load
      pressure is located in the safe region concerning infinite lifetime. 

PMID- 22587435
TI  - Extensive amyloid formation in transplanted microencapsulated mouse and human
      islets.
AB  - OBJECTIVE: Deposition of cell toxic islet amyloid is a frequent finding in type 2
      diabetes and also in transplanted human islets, where it is a possible
      explanation for their long-term failure. One suggested reason for amyloid in
      transplanted islets is that their low vascular density results in a disturbed
      local clearance of islet amyloid polypeptide (IAPP). To test this hypothesis we
      analysed accumulation of amyloid in microencapsulated islets, which exemplify a
      non-vascularised islet graft. METHODS: Isolated islets from human or transgenic
      mice expressing human IAPP were microencapsulated in alginate and cultured in
      vitro or transplanted under the kidney capsule of normoglycemic nude mice. The
      degree of amyloid was determined after Congo red staining and subcellular
      alterations were analysed with electron microscopy. RESULTS: Insulin and IAPP
      secretion from transgenic mouse islets were markedly increased during stimulation
      with glucose after one week of culture, but encapsulated islets in general
      released less insulin. Amyloid was detected after both one and three weeks of
      culture in the transgenic mouse islets and the encapsulated islets were most
      affected. After transplantation, electron microscopy displayed both intra- and
      extracellular amyloid in microencapsulated as well as in non-encapsulated human
      and transgenic mouse islet grafts. However, amyloid was more frequent in the
      encapsulated grafts. CONCLUSION: Micro-encapsulation of pancreatic islets might
      serve as an important tool for studies of amyloid formation under enhanced
      circumstances.

PMID- 22587436
TI  - Anti-angiogenesis effect of 3'-sulfoquinovosyl-1'-monoacylglycerol via
      upregulation of thrombospondin 1.
AB  - We previously reported that 3'-sulfoquinovosyl-1'-monoacylglycerol (SQMG)
      effectively suppresses the growth of solid tumors, likely via its anti-angiogenic
      activity. To investigate how SQMG affects angiogenesis, we performed DNA
      microarray analysis and quantitative real-time polymerase chain reaction.
      Consequently, upregulation of thrombospondin 1 (TSP-1) in SQMG-treated tumors in
      vitro and in vivo was confirmed. To address the mechanisms of TSP-1 upregulation
      by SQMG, we established stable TSP-1-knockdown transformants (TSP1-KT) by short
      hairpin RNA induction and performed reporter assay and in vivo assessment of anti
      tumor assay. On the reporter assay, transcriptional upregulation of TSP-1 in TSP1
      KT could not be induced by SQMG, thus suggesting that TSP-1 upregulation by SQMG
      occurred via TSP-1 molecule. In addition, growth of TSP1-KT xenografted tumors in
      vivo was not inhibited by SQMG, thus suggesting that anti-angiogenesis via TSP-1
      upregulation induced by SQMG did not occur, as the SQMG target molecule TSP-1 was
      knocked down in TSP1-KT transformants. These data provide that SQMG is a
      promising candidate for the treatment of tumor-induced angiogenesis via TSP-1
      upregulation.

PMID- 22587437
TI  - Mesopore-free hollow silica particles with controllable diameter and shell
      thickness via additive-free synthesis.
AB  - Mesopore-free hollow silica particles with a spherical shape, smooth surface, and
      controllable diameter (from 80 to 300 nm) and shell thickness (from 2 to 25 nm)
      were successfully prepared using an additive-free synthesis method. Different
      from other hollow particle developments, a mesopore-free shell was produced
      because of the absence of additive. Although common reports pointed out the
      importance of the additional additive in pasting and growing silica on the
      surface of a template, here we preferred to exploit the effect of the template
      charge in gaining the silica coating process. To form the silica, basic amino
      acid (i.e., lysine) was used as a catalyst to replace ammonia or hydrazine, which
      is harmless and able to control the silica growth and produce hollow particles
      with smooth surfaces. Control of the particle diameter was drastically achieved
      by altering the size of the template. The flexibility of the process in
      controlling the shell thickness was predominantly attained by varying the
      compositions of the reactants (i.e., silica source and catalyst). The present
      mesopore-free hollow particles could be efficiently used for various
      applications, especially for thermal insulator and optical devices because of
      their tendency not to adsorb large molecules, as confirmed by adsorption
      analysis.

PMID- 22587438
TI  - High molecular weight hyaluronan reduces lipopolysaccharide mediated microglial
      activation.
AB  - Toll-like receptor-4 (TLR4) signaling has been implicated in microglial
      activation and propagation of inflammation following spinal cord injury (SCI). As
      such, modulating microglial activation through TLR4 represents an attractive
      therapeutic approach to treat SCI. High molecular weight hyaluronan (HMW-HA), a
      polymer with multiple therapeutic uses, has been previously shown to modulate
      TLR4 activation in macrophages and has shown early promise as a therapeutic agent
      in SCI. However, the mechanism associated with HMW-HA has not been fully
      elucidated or tested in microglia, a similar cell type. In the current study, we
      sought to determine the effects of HMW-HA on TLR4 activation in microglia and to
      gain insights into the mechanism of action. Rat primary microglial cultures were
      exposed to lipopolysaccharides (LPS) and HMW-HA, and the extent and mechanisms of
      inflammation were studied. HMW-HA decreased LPS mediated IL-1beta, IL-6, and
      Tumor necrosis factor-alpha gene expression and IL-6 and nitric oxide production.
      This decrease was associated with a reduction in ERK 1/2 and p38 phosphorylation,
      was dependent on the continued presence of HMW-HA, and activation of Akt and A20
      protein expression was reduced by HMW-HA. Together, our results show that HMW-HA
      can reduce LPS-mediated inflammatory signaling in microglia. We suggest that HA
      possibly mediates its effects by blocking the induction of inflammatory signaling
      through an extracellular mechanism.

PMID- 22587439
TI  - Schwannoma of ascending colon treated by laparoscopic right hemicolectomy.
AB  - Schwannomas of the colon are rare and are difficult to diagnose preoperatively,
      since they often defy endoscopic and radiographic detection. Immunohistochemical
      stains are useful postoperatively to confirm this tumor, but more reliable
      diagnostic techniques (such as colonoscopic biopsy with immunohistochemistry)
      have emerged to enhance preoperative diagnostic accuracy. Here we report an
      instance of schwannoma arising in the ascending colon, where immunohistochemical
      staining of a preoperative biopsy facilitated diagnosis. After laparoscopic
      resection, histologic examination was confirmatory.

PMID- 22587441
TI  - Development and application of a loop-mediated isothermal amplification assay for
      rapid detection of Borrelia burgdorferi s. l. in ticks.
AB  - A loop-mediated isothermal amplification (LAMP) assay was developed to detect
      Borrelia burgdorferi s. l. in ticks, which is a pathogen that causes Lyme
      disease. Cross-reactions with Chlamydia psittaci, Mycoplasma mycoides subsp.
      capri and some tick-borne pathogens were excluded. Analytical sensitivity of LAMP
      showed its detection limit was from 0.02 to 0.2 pg of DNA in detection of the
      reference samples at 65 degrees C for 40 min. The performance of LAMP was
      assessed by testing 110 samples from susceptible tick species and comparing the
      results with conventional and nested PCR tests previously described. The results
      demonstrated that LAMP was significantly more sensitive than the conventional PCR
      (32.7% versus 15.5%, P < 0.05) and slightly more sensitive, although not
      significantly so, than nested PCR (32.7% versus 26.4%, P > 0.05). The assay was
      used to analyse a total of 1052 ticks collected from eight provinces in China.
      The results showed that the infection rates of B. burgdorferi s. l. varied from
      12.5% to 88.9% across the different geographical sites. Selected positive samples
      were subjected to sequencing and sequence analysis for conformation of the
      accuracy of the assay. Here we report a highly sensitive, specific and easy
      diagnostic assay based on LAMP technology. These data indicate that LAMP is a
      useful approach for detecting B. burgdorferi s. l. in field-collected ticks and
      has the potential as an alternative tool for the ecological and epidemiological
      surveillance of Lyme disease.

PMID- 22587440
TI  - A key role for Mg(2+) in TRPM7's control of ROS levels during cell stress.
AB  - The TRPM7 (transient receptor potential melastatin 7) channel has been shown to
      play a pivotal role in cell survival during brain ischaemia as well as in the
      survival of other cell types challenged with apoptotic stimuli. Ca(2+) is thought
      to be central to the channel's ability to regulate ROS (reactive oxygen species)
      production. However, channel-mediated entry of Mg(2+) and Zn(2+) have also been
      implicated in cell death. In the present study, we show that depletion of TRPM7
      by RNA interference in fibroblasts increases cell resistance to apoptotic stimuli
      by decreasing ROS levels in an Mg(2+)-dependent manner. Depletion of TRPM7
      lowered cellular Mg(2+), decreased the concentration of ROS and lessened p38 MAPK
      (mitogen-activated protein kinase) and JNK (c-Jun N-terminal kinase) activation
      as well as decreased caspase 3 activation and PARP [poly(ADP-ribose) polymerase]
      cleavage in response to apoptotic stimuli. Re-expression of TRPM7 or of a kinase
      inactive mutant of TRPM7 in TRPM7-knockdown cells increased cellular Mg(2+) and
      ROS levels, as did expression of the Mg(2+) transporter SLC41A2 (solute carrier
      family 41 member 2). In addition, expression of SLC41A2 increased the sensitivity
      of TRPM7-knockdown cells to apoptotic stimuli and boosted ROS generation in
      response to cell stress. Taken together, these data uncover an essential role for
      Mg(2+) in TRPM7's control of cell survival and in the regulation of cellular ROS
      levels.

PMID- 22587442
TI  - Tubal ligation, hysterectomy and ovarian cancer: A meta-analysis.
AB  - PURPOSE: The purpose of this meta-analysis was to determine the strength of the
      association between gynecologic surgeries, tubal ligation and hysterectomy, and
      ovarian cancer. METHODS: We searched the PubMed, Web of Science, and Embase
      databases for all English-language articles dated between 1969 through March 2011
      using the keywords "ovarian cancer" and "tubal ligation" or "tubal sterilization"
      or "hysterectomy." We identified 30 studies on tubal ligation and 24 studies on
      hysterectomy that provided relative risks for ovarian cancer and a p-value or 95%
      confidence interval (CI) to include in the meta-analysis. Summary RRs and 95% CIs
      were calculated using a random-effects model. RESULTS: The summary RR for women
      with vs. without tubal ligation was 0.70 (95%CI: 0.64, 0.75). Similarly, the
      summary RR for women with vs. without hysterectomy was 0.74 (95%CI: 0.65, 0.84).
      Simple hysterectomy and hysterectomy with unilateral oophorectomy were associated
      with a similar decrease in risk (summery RR = 0.62, 95%CI: 0.49-0.79 and 0.60,
      95%CI: 0.47-0.78, respectively). In secondary analyses, the association between
      tubal ligation and ovarian cancer risk was stronger for endometrioid tumors
      (summary RR = 0.45, 95%CI: 0.33, 0.61) compared to serous tumors. CONCLUSION:
      Observational epidemiologic evidence strongly supports that tubal ligation and
      hysterectomy are associated with a decrease in the risk of ovarian cancer, by
      approximately 26-30%. Additional research is needed to determine whether the
      association between tubal ligation and hysterectomy on ovarian cancer risk
      differs by individual, surgical, and tumor characteristics.

PMID- 22587443
TI  - Synthesis and structure-activity relationships of pyrazolo[1,5-a]pyridine
      derivatives: potent and orally active antagonists of corticotropin-releasing
      factor 1 receptor.
AB  - Design, synthesis, and structure-activity relationships of a series of 3
      dialkylamino-7-phenyl pyrazolo[1,5-a]pyridines (I) as selective antagonists of
      the corticotropin-releasing factor 1 (CRF(1)) receptor are described. The most
      prominent compound to emerge from this work, 46 (E2508), exhibits potent in vitro
      activity, excellent drug-like properties, and robust oral efficacy in animal
      models of stress-related disorders. It has advanced into clinical trials.

PMID- 22587444
TI  - Could basic research shed light on false positivity in photodynamic diagnosis?

PMID- 22587445
TI  - Do skeletal cephalometric characteristics correlate with condylar volume, surface
      and shape? A 3D analysis.
AB  - OBJECTIVE: The purpose of this study was to determine the condylar volume in
      subjects with different mandibular divergence and skeletal class using cone-beam
      computed tomography (CBCT) and analysis software. MATERIALS AND METHODS: For 94
      patients (46 females and 48 males; mean age 24.3 +/- 6.5 years), resultant
      rendering reconstructions of the left and right temporal mandibular joints (TMJs)
      were obtained.Subjects were then classified on the base of ANB angle the GoGn-SN
      angle in three classes (I, II, III) . The data of the different classes were
      compared. RESULTS: No significant difference was observed in the whole sample
      between the right and the left sides in condylar volume.The analysis of mean
      volume among low, normal and high mandibular plane angles revealed a
      significantly higher volume and surface in low angle subjects (p < 0.01) compared
      to the other groups.Class III subjects also tended to show a higher condylar
      volume and surface than class I and class II subjects, although the difference
      was not significant. CONCLUSIONS: Higher condylar volume was a common
      characteristic of low angle subjects compared to normal and high mandibular plane
      angle subjects. Skeletal class also appears to be associated to condylar volume
      and surface.

PMID- 22587446
TI  - Marker chromosomes.
AB  - Marker chromosomes are a morphologically heterogeneous group of structurally
      abnormal chromosomes that pose a significant challenge in prenatal diagnosis.
      Phenotypes associated with marker chromosomes are highly variable and range from
      normal to severely abnormal. Clinical outcomes are very difficult to predict when
      marker chromosomes are detected prenatally. In this review, we outline the
      classification, etiology, cytogenetic characterization, and clinical consequences
      of marker chromosomes, as well as practical approaches to prenatal diagnosis and
      genetic counseling.

PMID- 22587448
TI  - Structure & Expression, Volumes 1, 2 & 3.

PMID- 22587451
TI  - Upcoming New Feature in the Journal of Biomolecular Structure & Dynamics.

PMID- 22587453
TI  - Antipsychotic polypharmacy in a regional health service: a population-based
      study.
AB  - BACKGROUND: To analyse the extent and profile of outpatient regular dispensation
      of antipsychotics, both in combination and monotherapy, in the Barcelona Health
      Region (Spain), focusing on the use of clozapine and long-acting injections
      (LAI). METHODS: Antipsychotic drugs dispensed for people older than 18 and
      processed by the Catalan Health Service during 2007 were retrospectively
      reviewed. First and second generation antipsychotic drugs (FGA and SGA) from the
      Anatomical Therapeutic Chemical classification (ATC) code N05A (except lithium)
      were included. A patient selection algorithm was designed to identify
      prescriptions regularly dispensed. Variables included were age, gender,
      antipsychotic type, route of administration and number of packages dispensed.
      RESULTS: A total of 117,811 patients were given any antipsychotic, of whom 71,004
      regularly received such drugs. Among the latter, 9,855 (13.9%) corresponded to an
      antipsychotic combination, 47,386 (66.7%) to monotherapy and 13,763 (19.4%) to
      unspecified combinations. Of the patients given antipsychotics in association,
      58% were men. Olanzapine (37.1%) and oral risperidone (36.4%) were the most
      common dispensations. Analysis of the patients dispensed two antipsychotics
      (57.8%) revealed 198 different combinations, the most frequent being the
      association of FGA and SGA (62.0%). Clozapine was dispensed to 2.3% of patients.
      Of those who were receiving antipsychotics in combination, 6.6% were given
      clozapine, being clozapine plus amisulpride the most frequent association
      (22.8%). A total of 3.800 patients (5.4%) were given LAI antipsychotics, and
      2.662 of these (70.1%) were in combination. Risperidone was the most widely used
      LAI. CONCLUSIONS: The scant evidence available regarding the efficacy of
      combining different antipsychotics contrasts with the high number and variety of
      combinations prescribed to outpatients, as well as with the limited use of
      clozapine.

PMID- 22587455
TI  - Pain management in dermatologic procedures: before and after.
AB  - BACKGROUND: Periprocedural analgesic therapy is an often overlooked, but critical
      component of ensuring adequate surgical patient care and overall satisfaction
      with surgical outcomes. Adequate pain management requires thorough assessment of
      pain and complete knowledge and understanding of the various therapeutic agents
      available. OBJECTIVES: To further the knowledge and understanding of current
      strategies in pain management. METHODS: A literature review was conducted through
      PubMed to define current pain assessment and management strategies. RESULTS AND
      CONCLUSIONS: Appropriate pain assessment leads to the selection of optimal
      pharmacologic options for pain control in the acute postoperative setting.

PMID- 22587454
TI  - Dynamics of metastable beta-hairpin structures in the folding nucleus of amyloid
      beta-protein.
AB  - The amyloid beta-protein (Abeta), which is present predominately as a 40- or 42
      residue peptide, is postulated to play a seminal role in the pathogenesis of
      Alzheimer's disease (AD). Folding of the Abeta(21-30) decapeptide region is a
      critical step in the aggregation of Abeta. We report results of constant
      temperature all-atom molecular dynamics simulations in explicit water of the
      dynamics of monomeric Abeta(21-30) and its Dutch [Glu22Gln], Arctic [Glu22Gly],
      and Iowa [Asp23Asn] isoforms that are associated with familial forms of cerebral
      amyloid angiopathy and AD. The simulations revealed a variety of loop conformers
      that exhibited a hydrogen bond network involving the Asp23 and Ser26 amino acids.
      A population of conformers, not part of the loop population, was found to form
      metastable beta-hairpin structures with the highest probability in the Iowa
      mutant. At least three beta-hairpin structures were found that differed in their
      hydrogen bonding register, average number of backbone hydrogen bonds, and
      lifetimes. Analysis revealed that the Dutch mutant had the longest beta-hairpin
      lifetime (>=500 ns), closely followed by the Iowa mutant (~500 ns). Abeta(21-30)
      and the Arctic mutant had significantly lower lifetimes (~200 ns). Hydrophobic
      packing of side chains was responsible for enhanced beta-hairpin lifetimes in the
      Dutch and Iowa mutants, whereas lifetimes in Abeta(21-30) and its Arctic mutant
      were influenced by the backbone hydrogen bonding. The data suggest that prolonged
      beta-hairpin lifetimes may impact peptide pathogenicity in vivo.

PMID- 22587456
TI  - Predictors of decrease in ankle-brachial index among patients with diabetes
      mellitus.
AB  - AIM: Screening for peripheral arterial disease, a complication among patients
      with diabetes, is performed by periodic assessment of ankle-brachial index. We
      aimed to study the degree of ankle-brachial index change over time and factors
      associated with significant change. METHOD: We assessed difference between two
      ankle-brachial index measurements over time in a consecutive series of 82
      patients with Type 2 diabetes. All patients had ankle-brachial index > 0.9 but <=
      1.3 for the first measurement, and significant ankle-brachial index decrease was
      defined as a decrease of > 0.1 in the follow-up measurement compared with the
      baseline. RESULTS: The mean follow-up duration was 27.6 (median 30.0) months.
      Significant ankle-brachial index decrease was seen in 20.7% of patients,
      including 5% with follow-up ankle-brachial index of <= 0.9, consistent with the
      diagnosis of peripheral arterial disease. After adjusting for age and gender,
      higher baseline HbA(1c) and serum creatinine levels, increase in follow-up serum
      LDL cholesterol levels compared with baseline and history of retinopathy were
      predictors of significant ankle-brachial index decrease. CONCLUSIONS: Our study
      suggests that, within two years, one in five patients with diabetes and a normal
      ankle-brachial index may have significant progression of peripheral arterial
      disease. Annual ankle-brachial index assessment and better control of
      hyperlipidaemia may thus be required for at-risk patients with poor glycaemic
      control, renal impairment and retinopathy.

PMID- 22587457
TI  - Phase I study of TAC-101, an oral synthetic retinoid, in Japanese patients with
      advanced hepatocellular carcinoma.
AB  - Preclinical models have shown that TAC-101 (4-[3,5-bis(trimethylsilyl) benzamide]
      benzoic acid), an oral synthetic retinoid, has antitumor activity in
      hepatocellular carcinoma (HCC). We conducted a phase I study in Japanese patients
      with advanced HCC to examine the pharmacokinetics, recommended dose, safety, and
      efficacy of TAC-101. The administered dose of TAC-101 was 10 mg/day in four
      patients (level 1), 20 mg/day in six (level 2), and 30 mg/day in three (level 3).
      There was no dose-limiting toxicity at level 1. Only one patient each had dose
      limiting toxicity at level 2 (grade 2 fatigue, recovery requiring eight or more
      consecutive days of rest) and at level 3 (grade 3 splenic vein thrombosis). Level
      3 (30 mg/day) was considered the maximum tolerated dose and 20 mg/day the
      recommended dose by a panel of medical experts, placing maximum emphasis on
      safety. The most frequent adverse events were fatigue, headache, and dermal
      symptoms such as rash. Pharmacokinetic parameters in Japanese patients with HCC
      were similar to those in patients in the United States, most of whom were
      Caucasian. Although no patient had a complete or partial response, the disease
      control rate was 38.5%. In conclusion, the recommended dose of TAC-101 for
      patients with HCC is 20 mg/day. TAC-101 had an acceptable toxicity profile,
      warranting further evaluation in clinical trials.

PMID- 22587458
TI  - Arrhythmia--a pitfall in tests of cardiac autonomic function after liver
      transplantation for familial amyloidotic polyneuropathy: a long-term follow-up of
      Swedish patients.
AB  - Liver transplantation (LT) is a potentially curative treatment for hereditary
      transthyretin amyloidosis, of which familial amyloid polyneuropathy (FAP) is the
      most common form in Sweden. This study investigated the long-term development in
      heart rate variability (HRV) after LT in Swedish FAP patients. HRV was analyzed
      before LT, and during a first (<40 months) and a second (>40 months) follow-up
      recording after transplantation, respectively. Power spectrum analysis was
      performed on 2-min sequences in the supine position and after passive tilt, after
      careful identification of patients with arrhythmia. Data were obtained from 33
      patients, but 18 patients had developed cardiac arrhythmia or were pacemaker
      treated (4 before LT and 14 after LT) and three patients had not performed the
      first follow-up recording. In the remaining 12 patients, HRV decreased between
      the pretransplant evaluation and the first follow-up, thereafter no significant
      changes were found. In conclusion, our study showed that the progressive
      development of cardiac arrhythmias after LT is a major pitfall when assessing
      cardiac autonomic function in FAP patients, especially in patients older than 40
      years. In the minority of patients with sinus rhythm in all recordings, cardiac
      autonomic modulation remained stable after transplantation and no improvement was
      noted.

PMID- 22587459
TI  - New section in journal of translational medicine: patient-targeted molecular
      therapies.
AB  - This Editorial announces a new section in the Journal of Translational Medicine:
      Patient-Targeted Molecular Therapies. This section is dedicated to the
      dissemination of targeted molecular therapies in context of patient-centered
      outcomes research and evidence-based clinical decisions. The focus on patient
      targeted molecular therapies - spanning small molecules and biomolecules alike -
      stems from the unprecedented growth in this arena. This is consonant with the
      overall objective of the Journal of Translational Medicine, which seeks out to
      expand firmly to other vast areas of medicine in the domain of translational
      science, viewed here as the transaction between translational research and
      translational effectiveness. As we inaugurate this new section in Journal of
      Translational Medicine, with its mission described in detail in this Editorial,
      we invite interested scientists to submit their work for publication.

PMID- 22587460
TI  - Role of the junctional epithelium in periodontal innate defense and homeostasis.
AB  - BACKGROUND AND OBJECTIVE:   The junctional epithelium provides the front-line
      defense against periodontal bacterial infection. The migration of neutrophils
      into the junctional epithelium might represent a protective reaction against
      bacterial infections. However, neutrophils penetrate into the junctional
      epithelium even under sterile conditions. In this study, we analyzed and compared
      the number of neutrophils and the cytokine expression related to neutrophil
      migration in the junctional epithelium in conventional and germ-free mice.
      MATERIAL AND METHODS:   Germ-free and conventional ICR mice were used at 12 wk of
      age. Frozen sections were used for the detection of Gr-1, macrophage inflammatory
      protein-2 (MIP-2/CXCL2) and proliferating cell nuclear antigen-positive cells in
      the two groups of mice. Laser capture microdissection and RT-PCR analysis were
      used to evaluate the expression of keratinocyte-derived chemokine (KC/CXCL1), MIP
      2, interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) mRNAs
      in the two groups of mice. RESULTS:   Morphometric examination indicated an
      increase in the area of the junctional epithelium upon bacterial infection.
      Immunohistochemical studies also detected an increased number of neutrophils in
      the junctional epithelium upon bacterial infection. Higher up-regulation of KC
      and MIP-2 were detected in the junctional epithelium of conventional mice than in
      germ-free mice, whereas the expression of Il-1beta and Tnfalpha mRNAs was not
      affected. CONCLUSION:   Junctional epithelium cells constitutively expressed
      several types of chemokines and cytokines and the expression of chemokines was
      augmented by bacterial infection. Therefore, the constitutive expression of
      cytokines in junctional epithelium might be related to the morphological and
      functional homeostasis of the junctional epithelium in addition to the defense
      against the bacterial infection.

PMID- 22587462
TI  - Detecting internet activity for erectile dysfunction using search engine query
      data in the Republic of Ireland.
AB  - What's known on the subject? and What does the study add? Despite the increasing
      prevalence of erectile dysfunction (ED), there is reluctance among symptomatic
      patients to present to healthcare providers for appropriate advice and treatment.
      A number of Internet campaigns have been launched by the Irish healthcare media
      since 2007 aiming to provide easily accessible advice on ED. Novel online
      technologies appear to provide a useful tool for educating the general public on
      the symptoms of ED because there has been a significant increase in overall
      Internet search activity for this term since 2007. OBJECTIVES: * To assess
      Internet search trends for erectile dysfunction (ED) subsequent to public
      awareness campaigns being launched within the Republic of Ireland * To assess
      whether the advent of such campaigns correlates with increased Internet search
      activity for ED. MATERIALS AND METHODS: * Google insights for search was utilized
      to examine Internet search trends for the term 'erectile dysfunction' across all
      categories between January 2005 and December 2011. * Search activity was limited
      to users from the Republic of Ireland within this timeframe. * Additionally, the
      number of Irish Internet media campaigns and Irish web pages providing
      information on ED was assessed between January 2005 and December 2011. *
      Statistical analysis of the data was performed using analysis of variance and
      Student's t-tests for pairwise comparisons. RESULTS: * There has been a
      significant increase in mean search activity for ED on an annual basis since 2007
      (P < 0.001). * The number of Irish web pages associated with information on ED
      has also increased significantly on an annual basis since 2007 (P < 0.001). *
      There have been seven different Irish Internet media campaigns on ED since 2007
      compared to two from 2005 to 2007 (P < 0.001). * There was no significant change
      in mean search activity for ED from 2005 to 2007 CONCLUSIONS: * The advent of
      recent Internet media campaigns and increasing number of Irish web pages is
      associated with a significant increase in online activity for ED in the Republic
      of Ireland. * Novel online technologies appear to provide a useful tool for
      educating the general public on the symptoms and treatment options available for
      ED.

PMID- 22587463
TI  - Size-controlled electrochemical growth of PbS nanostructures into
      electrochemically patterned self-assembled monolayers.
AB  - 1-Hexadecanethiol self-assembled monolayers (HDT SAMs) on Au(111) were used as a
      molecular resist to fabricate nanosized patterns by electrochemical reductive
      partial desorption for subsequent electrodeposition of PbS from the same solution
      simultaneously. The influences of potential steps of variable pulse width and
      amplitude on the size and the number of patterns were investigated. The kinetics
      of pattern formation by reductive desorption appears to be instantaneous
      according to chronoamperometric and morphological investigations. PbS structures
      were deposited electrochemically into the patterns on HDT SAMs by a combined
      electrochemical technique, based on the codeposition from the same saturated PbS
      solution at the underpotential deposition of Pb and S. Scanning tunneling
      microscopy measurements showed that all of the PbS deposits were disk shaped and
      uniformly distributed on Au(111) surfaces. Preliminary results indicated that the
      diameter and the density of PbS deposits can be controlled by controlling the
      pulse width and amplitude of potential applied at the reductive removal stage of
      HDT SAMs and the deposition time during the electrochemical deposition step.

PMID- 22587461
TI  - Recruitment and membrane interactions of host cell proteins during attachment of
      enteropathogenic and enterohaemorrhagic Escherichia coli.
AB  - EPEC (enteropathogenic Escherichia coli) and EHEC (enterohaemorrhagic Escherichia
      coli) are attaching and effacing pathogens frequently associated with infectious
      diarrhoea. EPEC and EHEC use a T3SS (type III secretion system) to translocate
      effectors that subvert different cellular processes to sustain colonization and
      multiplication. The eukaryotic proteins NHERF2 (Na(+)/H(+) exchanger regulatory
      factor 2) and AnxA2 (annexin A2), which are involved in regulation of intestinal
      ion channels, are recruited to the bacterial attachment sites. Using a stable
      HeLa-NHERF2 cell line, we found partial co-localization of AnxA2 and NHERF2; in
      EPEC-infected cells, AnxA2 and NHERF2 were extensively recruited to the site of
      bacterial attachment. We confirmed that NHERF2 dimerizes and found that NHERF2
      interacts with AnxA2. Moreover, we found that AnxA2 also binds both the N- and C
      terminal domains of the bacterial effector Tir through its C-terminal domain.
      Immunofluorescence of HeLa cells infected with EPEC showed that AnxA2 is
      recruited to the site of bacterial attachment in a Tir-dependent manner, but
      independently of Tir-induced actin polymerization. Our results suggest that AnxA2
      and NHERF2 form a scaffold complex that links adjacent Tir molecules at the
      plasma membrane forming a lattice that could be involved in retention and
      dissemination of other effectors at the bacterial attachment site.

PMID- 22587464
TI  - Self-expanding stent modelling and radial force accuracy.
AB  - Computational simulations using finite element analysis are a tool commonly used
      to analyse stent designs, deployment geometries and interactions between stent
      struts and arterial tissue. Such studies require large computational models and
      efforts are often made to simplify models in order to reduce computational time
      while maintaining reasonable accuracy. The objective of the study is focused on
      computational modelling and specifically aims to investigate how different
      methods of modelling stent-artery interactions can affect the results,
      computational time taken and computational size of the model. Various different
      models, each with increasing levels of complexity, are used to simulate this
      analysis, representing the many assumptions and simplifications used in other
      similar studies in order to determine what level of simplification will still
      allow for an accurate representation of stent radial force and resulting stress
      concentrations on the inner lining of the vessel during self-expanding stent
      deployment. The main conclusions of the study are that methods used in stent
      crimping impact on the resulting predicted radial force of the stent; that
      accurate representation of stent-artery interactions can only be made when
      modelling the full length of the stent due to the incorporation of end effects;
      and that modelling self-contact of the stent struts greatly impacts on the
      resulting stress concentrations within the stent, but that the effect of this on
      the unloading behaviour and resulting radial force of the stent is negligible.

PMID- 22587465
TI  - Identification of HIV-1 inhibitors targeting the nucleocapsid protein.
AB  - The HIV-1 nucleocapsid (NC) is a RNA/DNA binding protein encoded within the Gag
      polyprotein, which is critical for the selection and chaperoning of viral genomic
      RNA during virion assembly. RNA/DNA binding occurs through a highly conserved
      zinc-knuckle motif present in NC. Given the necessity of NC-viral RNA/DNA
      interaction for viral replication, identification of compounds that disrupt the
      NC-RNA/DNA interaction may have value as an antiviral strategy. To identify small
      molecules that disrupt NC-viral RNA/DNA binding, a high-throughput fluorescence
      polarization assay was developed and a library of 14,400 diverse, druglike
      compounds was screened. Compounds that disrupted NC binding to a fluorescence
      labeled DNA tracer were next evaluated by differential scanning fluorimetry to
      identify compounds that must bind to NC or Gag to impart their effects. Two
      compounds were identified that inhibited NC-DNA interaction, specifically bound
      NC with nanomolar affinity, and showed modest anti-HIV-1 activity in ex vivo cell
      assays.

PMID- 22587466
TI  - Prognostic factors in canine appendicular osteosarcoma - a meta-analysis.
AB  - BACKGROUND: Appendicular osteosarcoma is the most common malignant primary canine
      bone tumor. When treated by amputation or tumor removal alone, median survival
      times (MST) do not exceed 5 months, with the majority of dogs suffering from
      metastatic disease. This period can be extended with adequate local intervention
      and adjuvant chemotherapy, which has become common practice. Several prognostic
      factors have been reported in many different studies, e.g. age, breed, weight,
      sex, neuter status, location of tumor, serum alkaline phosphatase (SALP), bone
      alkaline phosphatase (BALP), infection, percentage of bone length affected,
      histological grade or histological subtype of tumor. Most of these factors are,
      however, only reported as confounding factors in larger studies. Insight in truly
      significant prognostic factors at time of diagnosis may contribute to tailoring
      adjuvant therapy for individual dogs suffering from osteosarcoma. The objective
      of this study was to systematically review the prognostic factors that are
      described for canine appendicular osteosarcoma and validate their scientific
      importance. RESULTS: A literature review was performed on selected studies and
      eligible data were extracted. Meta-analyses were done for two of the three
      selected possible prognostic factors (SALP and location), looking at both
      survival time (ST) and disease free interval (DFI). The third factor (age) was
      studied in a qualitative manner. Both elevated SALP level and the (proximal)
      humerus as location of the primary tumor are significant negative prognostic
      factors for both ST and DFI in dogs with appendicular osteosarcoma. Increasing
      age was associated with shorter ST and DFI, however, was not statistically
      significant because information of this factor was available in only a limited
      number of papers. CONCLUSIONS: Elevated SALP and proximal humeral location are
      significant negative prognosticators for canine osteosarcoma.

PMID- 22587467
TI  - Mutagenicity of diesel engine exhaust is eliminated in the gas phase by an
      oxidation catalyst but only slightly reduced in the particle phase.
AB  - Concerns about adverse health effects of diesel engine emissions prompted strong
      efforts to minimize this hazard, including exhaust treatment by diesel oxidation
      catalysts (DOC). The effectiveness of such measures is usually assessed by the
      analysis of the legally regulated exhaust components. In recent years additional
      analytical and toxicological tests were included in the test panel with the aim
      to fill possible analytical gaps, for example, mutagenic potency of polycyclic
      aromatic hydrocarbons (PAH) and their nitrated derivatives (nPAH).  This
      investigation focuses on the effect of a DOC on health hazards from combustion of
      four different fuels: rapeseed methyl ester (RME), common mineral diesel fuel
      (DF), SHELL V-Power Diesel (V-Power), and ARAL Ultimate Diesel containing 5% RME
      (B5ULT). We applied the European Stationary Cycle (ESC) to a 6.4 L turbo-charged
      heavy load engine fulfilling the EURO III standard. The engine was operated with
      and without DOC. Besides regulated emissions we measured particle size and number
      distributions, determined the soluble and solid fractions of the particles and
      characterized the bacterial mutagenicity in the gas phase and the particles of
      the exhaust.  The effectiveness of the DOC differed strongly in regard to the
      different exhaust constituents: Total hydrocarbons were reduced up to 90% and
      carbon monoxide up to 98%, whereas nitrogen oxides (NO(X)) remained almost
      unaffected. Total particle mass (TPM) was reduced by 50% with DOC in common
      petrol diesel fuel and by 30% in the other fuels. This effect was mainly due to a
      reduction of the soluble organic particle fraction. The DOC caused an increase of
      the water-soluble fraction in the exhaust of RME, V-Power, and B5ULT, as well as
      a pronounced increase of nitrate in all exhausts. A high proportion of ultrafine
      particles (10-30 nm) in RME exhaust could be ascribed to vaporizable particles.
      Mutagenicity of the exhaust was low compared to previous investigations. The DOC
      reduced mutagenic effects most effectively in the gas phase. Mutagenicity of
      particle extracts was less efficiently diminished. No significant differences of
      mutagenic effects were observed among the tested fuels. In conclusion, the
      benefits of the DOC concern regulated emissions except NO(X) as well as
      nonregulated emissions such as the mutagenicity of the exhaust. The reduction of
      mutagenicity was particularly observed in the condensates of the gas phase. This
      is probably due to better accessibility of gaseous mutagenic compounds during the
      passage of the DOC in contrast to the particle-bound mutagens. Concerning the
      particulate emissions DOC especially decreased ultrafine particles.

PMID- 22587468
TI  - Ultra wide field fluorescein angiography can detect macular pathology in central
      retinal vein occlusion.
AB  - The purpose of this study was to evaluate whether ultra wide field fluorescein
      angiography (UWFFA), a tool established for the detection of peripheral non
      perfusion, can also detect macular pathology. A retrospective imaging review was
      performed on patients with central retinal vein occlusion. UWFFA was graded for
      angiographic leakage (petalloid and/or diffuse leakage) and presence of
      abnormalities in the foveal avascular zone and was then correlated to spectral
      domain optical coherence tomography (SD-OCT). Sixty-six eyes met inclusion
      criteria. Intergrader agreement was highly reliable for grading macular leakage
      on UWFFA (kappa = 0.75) and moderately reliable for the evaluation of an abnormal
      foveal avascular zone (kappa = 0.43). Angiographic leakage on UWFFA correlated to
      macular edema on SD-OCT (P > .0001), and abnormalities in the foveal avascular
      zone on UWFFA correlated to ganglion cell layer atrophy on SD-OCT (P = .0002).
      Intergrader reliability in grading UWFFA was better when assessing macular
      leakage than when assessing macular ischemia. UWFFA findings correlated to
      macular edema and signs of macular ischemia on SD-OCT.

PMID- 22587469
TI  - Assessment of cellular immune parameters in paediatric toxic shock syndrome: a
      report of five cases.
AB  - Toxic shock syndrome (TSS) and septic shock (SS) share many clinical signs of an
      exacerbated inflammatory response. In this report, we investigated whether TSS
      presents similar features of delayed immunosuppression as described in SS. Five
      children with TSS from paediatric intensive care units in a university hospital
      were monitored. TSS cases were defined by the association of standardized
      clinical signs of TSS and confirmed by measurement of specific Vbeta expansions
      corresponding to toxin gene profile of the isolated strains. As in SS, an
      increased percentage of circulating regulatory T cells (Treg) was observed in
      patients with TSS. However, in contrast to SS, neither lymphopenia nor decreased
      HLA-DR expression on monocytes was measured. In conclusion, whereas SS and TSS
      exhibited similar clinical presentation, the present observation suggests that
      respective pathophysiological mechanisms induce different immune alterations.
      Future studies must isolate and better characterize the phenotypic and functional
      properties of Treg subsets during TSS to understand the mechanisms sustaining
      their increase, especially the putative role of superantigens.

PMID- 22587470
TI  - Eratum, Volume 5.

PMID- 22587473
TI  - Structure & Expression, Volumes 1, 2 & 3.

PMID- 22587476
TI  - Upcoming New Feature in the Journal of Biomolecular Structure & Dynamics.

PMID- 22587478
TI  - Synthesis, high-resolution millimeter-wave spectroscopy, and ab initio
      calculations of ethylmercury hydride.
AB  - The millimeter-wave rotational spectrum of an organomercury compound,
      ethylmercury hydride, has been recorded and assigned for the first time. The
      spectroscopic study is complemented by quantum chemical calculations taking into
      account relativistic effects on the mercury atom. The very good agreement between
      theoretical and experimental molecular parameters validates the chosen ab initio
      method, in particular its capability to predict accurate quartic centrifugal
      distortion constants related to this type of compound. Estimations of the nuclear
      quadrupole coupling constants have less predictive power than those of the
      structural parameters, but are good enough to satisfy the spectroscopic needs. In
      addition, the orientation of the axis of the H-Hg-C bonds deduced from the
      experimental nuclear quadrupole coupling constants compares well with the
      corresponding ab initio value. From the good agreement between experimental and
      theoretical results, together with the observation of the six most abundant
      isotopes of mercury, ethylmercury hydride is unambiguously identified as the
      product of the chemical reaction described here, and its calculated equilibrium
      geometry is confirmed.

PMID- 22587479
TI  - CONCERN: Does ovary need D-chiro-inositol?
AB  - BACKGROUND: Polycystic Ovary Syndrome (PCOS) is a multifactorial pathology that
      affects 10% of the women in reproductive age being the main cause of infertility
      due to menstrual dysfunction. Since 1980, it is known that PCOS is associated
      with insulin resistance (IR). The recognition of this association has prompted
      extensive investigation on the relationship between insulin and gonadal function,
      and has turned insulin sensitizer agent as the main therapeutic choice. In
      particular two different polyalcohol myo-inositol and D-chiro-inositol have been
      shown to improve insulin resistance, hyperandrogenism and to induce ovulation in
      PCOS women. In particular, while data on myo-inositol and restored ovulation were
      consistent, data on D-chiro-inositol were not . Recently, a comparative study,
      proposed a D-chiro-inositol paradox in the ovary of PCOS patients hypothesizing
      that only myo-inositol has a specific ovarian action. In the present study we aim
      to further study the role played by D-chiro-inositol at ovarian level. METHODS: A
      total of 54 women, aged <40 years and diagnosed with PCOS were enrolled in this
      study. Patients with insulin resistance and/or hyperglycaemia were excluded from
      the study. Patients were randomly divided into 5 groups (n=10-12): a placebo
      group, and 4 groups (A-D) that received 300-600-1200-2400 mg of DCI daily
      respectively. All treatments were carried out for 8 weeks before follicle
      stimulating hormone (rFSH) administration. RESULTS: Total r-FSH units increased
      significantly in the two groups that received the higher doses of DCI. The number
      of immature oocytes was significantly increased in the three groups that received
      the higher doses of DCI. Concurrently, the number of MII oocytes was
      significantly lower in the D group compared to placebo group. Noteworthy, the
      number of grade I embryos was significantly reduced by DCI supplementation.
      CONCLUSIONS: Indeed, increasing DCI dosage progressively worsens oocyte quality
      and ovarian response.

PMID- 22587480
TI  - Tumor hormone/HER2 receptor status and pharmacologic treatment of metastatic
      breast cancer in Western Europe.
AB  - INTRODUCTION: Tumor hormone receptor (HR) and human epidermal growth factor
      receptor 2 (HER2) expression are important factors influencing treatment response
      and selection in patients with metastatic breast cancer (mBC). Using the LifeLink
      Oncology Analyzer Database, we classified mBC patients by combined HR and HER2
      status, and evaluated the use of pharmacological treatment modalities both
      overall and within these subtypes in Western Europe. PATIENTS AND METHODS: The
      study population included 4670 women with mBC from five Western European
      countries (France, Germany, Italy, Spain, UK). The most recent treatment
      administered (use of chemotherapy, endocrine therapy, HER2-targeted therapy, or
      others) and tumor marker (HR and HER2) status were captured. The results were
      summarized descriptively by combined tumor receptor status, current therapy type
      at the time of the survey, and age. RESULTS: Combined tumor receptor status and
      the most recent treatment for mBC were known for 4070 and 4060 women,
      respectively. The proportion of patients with each subtype ranged from 12.6-53.5%
      of the overall population (HR-/HER2+ least common and HR+/HER2- most common).
      Overall, chemotherapy was the most frequently reported treatment used followed by
      endocrine therapy and HER2-targeted therapy (59%, 33% and 15% of patients,
      respectively). Patients aged <=55 years were more likely to receive chemotherapy
      and less likely to receive endocrine treatment compared with patients aged >55.
      Patterns of treatment also differed by combined tumor receptor status and age
      although chemotherapy was consistently the mainstay of treatment. These results
      should be reviewed in light of the study limitations, including the cross
      sectional nature of data, the heterogeneity of our mBC population (newly
      metastasized vs. extensively treated), and the variations in receptor status
      evaluation among participating centers. CONCLUSIONS: Our analysis highlights the
      heterogeneity of the mBC population in Europe and illustrates that treatment
      modalities differed by age and by combined HR/HER2 receptor status.

PMID- 22587481
TI  - An assessment of the efficacy and safety of diclofenac potassium liquid-filled
      capsules in patients with various levels of baseline pain intensity.
AB  - CONTEXT: Diclofenac potassium liquid-filled soft gelatin capsule (DPSGC; Zipsor*)
      is a novel formulation of diclofenac potassium used to treat mild to moderate
      acute pain. OBJECTIVE: To investigate whether DPSGC 25 mg provided significant
      reduction in pain intensity compared with placebo, regardless of baseline pain
      intensity, a post hoc analysis was performed of pooled data from two replicate
      randomized controlled trials (NCT00366444 and NCT00375934) that evaluated the
      safety and efficacy of DPSGC in postbunionectomy treatment. METHODS: Patients
      from the two randomized trials were assigned to one of two subgroups: patients
      with baseline numerical pain rating scale (NPRS) scores of 4 or greater to less
      than 7 and those with baseline NPRS scores of 7 or greater. Within each subgroup,
      efficacy and safety of DPSGC was compared with placebo. RESULTS: Across the two
      studies, 73 DPSGC- and 59 placebo-treated patients had baseline pain intensity
      scores ranging from 4 or greater to less than 7, while 128 DPSGC- and 141 placebo
      treated patients had baseline pain intensity scores of 7 or greater.
      Significantly lower mean 48-hour NPRS scores were observed in the DPSGC group,
      regardless of baseline pain intensity (P < 0.0001). In both subgroups, at least
      twice as many patients treated with DPSGC rated the study drug as very good or
      excellent compared with patients taking placebo. Potential limitations for this
      post hoc analysis include study design and patient population. As with all
      studies investigating treatment for pain, the use of rescue medication may also
      be a potential limitation. CONCLUSIONS: DPSGC provided significantly greater
      improvements in pain compared with placebo following bunionectomy, regardless of
      patients' baseline pain level.

PMID- 22587482
TI  - Valproate-induced hyperammonemic encephalopathy: a brief review.
AB  - BACKGROUND: This brief review presents a comprehensive evaluation of valproate
      induced encephalopathy (VHE) and also discusses potential mechanisms of the
      condition. SCOPE: Sodium valproate (VPA) is an effective antiepileptic drug used
      in neurology as well as in psychiatry, in adults and children. VHE requires early
      diagnosis and management. Focused research efforts in understanding the condition
      will help decrease its incidence. Delay in recognition of VHE can result in the
      development of potentially life-threatening complications. FINDINGS: Management
      options are described. Since VPA frequently causes a modest rise in plasma
      ammonia levels which is asymptomatic, it is important to recognize the symptoms
      of VHE promptly and to correlate them with the plasma ammonia levels.
      CONCLUSIONS: Although there are several case reports on VHE, this review is a
      comprehensive evaluation of its causes and potential mechanisms. Rapid diagnosis
      and management will help in reducing VHE-related morbidity.

PMID- 22587483
TI  - Efficacy and tolerability of rosiglitazone and pioglitazone in drug-naive
      Japanese patients with type 2 diabetes mellitus: a double-blind, 28 weeks'
      treatment, comparative study.
AB  - OBJECTIVE: A 28-week, randomized, placebo-controlled study was performed to
      evaluate efficacy and tolerability of rosiglitazone in Japanese type 2 diabetes
      patients. RESEARCH AND DESIGN METHODS: 373 patients were randomized to
      rosiglitazone (4-8 mg/day), pioglitazone (15-45 mg/day) or placebo. Agents were
      titrated to maximum doses at fixed time points in a pre-defined manner. Primary
      endpoints were superiority of each active treatment compared to placebo in
      HbA(1c) at week 16, and non-inferiority between active agents in HbA(1c) at week
      28, based on a -0.45% margin. RESULTS: At week 16, improvements versus placebo
      were observed with rosiglitazone 4 mg/day (-0.96%, p < 0.001) and pioglitazone 30
      mg/day (-1.26%, p < 0.001). At week 28, rosiglitazone and pioglitazone were
      associated with significant changes from baseline of -0.94% and -1.35%,
      respectively and rosiglitazone produced statistically and clinically significant
      improvement versus placebo (-1.29%, CI: -1.62, -0.97). Pioglitazone also showed
      significant improvement versus placebo (-1.64%, CI: -1.96, -1.31). Non
      inferiority of rosiglitazone (4-8 mg/day) to pioglitazone (30-45 mg/day) was not
      demonstrated (treatment-difference: -0.41%, 95% CI: -0.64, -0.18). More patients
      treated with pioglitazone were withdrawn from the study by adverse events
      compared with rosiglitazone (14 vs. 4, p = 0.015). Pioglitazone was associated
      with higher incidences of adverse events relating to edema and weight gain
      compared with rosiglitazone (edema: 25.2 vs. 11.3%, weight gain: 9.4 vs. 4.4%).
      There were no reports of ischemic heart disease or congestive heart failure in
      any treatment group. CONCLUSION: Although non-inferiority to pioglitazone up to
      45 mg in efficacy was not shown, rosiglitazone was confirmed to have clinically
      meaningful efficacy over placebo and fewer fluid-related events than
      pioglitazone. The study is registered on ClinicalTrials.gov as protocol
      NCT00297063.

PMID- 22587484
TI  - Leukocidin genes lukF-P83 and lukM are associated with Taphylococcus aureus
      clonal complexes 151, 479 and 133 isolated from bovine udder infections in
      Thuringia, Germany.
AB  - Staphylococcus aureus is one of the most important causal agents of bovine
      mastitis. Population studies on bovine Staphylococcus aureus isolates have
      identified considerable genetic heterogeneity among strains causing mastitis. The
      aim of this study was to investigate the contribution of different clonal
      complexes and the occurrence of virulence factors and resistance determinants
      within bovine Staphylococcus aureus isolates.A total of 189 Staphylococcus aureus
      isolates obtained from milk samples of 34 dairy herds in the German Federal State
      of Thuringia were characterised by microarray technology.The isolates were
      assigned to eleven different clonal complexes with CC151, CC479 and CC133 being
      dominant (together 80.5%). The methicillin resistance gene mecA was found in four
      isolates (2.1%), which belonged to CC398. Enterotoxin genes could be detected in
      79.3% of analysed Staphylococcus aureus and 19 isolates (10.1%) harboured a
      distinct allele of the toxic shock syndrome toxin gene, tst-RF122. The most
      striking finding of the present study was that almost all except one isolate
      (151/152) belonging to CC151, CC479 and CC133 harboured the leukocidin genes lukF
      P83 and lukM, whereas no further isolates from other lineages possessed these
      genes.The consistent occurrence of lukF-P83/lukM in the dominating clonal
      complexes suggests an essential role of this leukocidin in the etiology of bovine
      mastitis.

PMID- 22587486
TI  - Proliferating pilar tumor of the scalp.

PMID- 22587487
TI  - A microscopic model of singlet fission.
AB  - Singlet fission, where an electronically excited singlet on one chromophore
      converts into a doubly excited state on two, has gone from a curiosity in organic
      photophysics to a potential pathway for increasing solar energy conversion
      efficiencies. Focusing on the role of solvent-induced energy level fluctuations
      that would be present in a dye-sensitized solar cell, we present a microscopic
      model for singlet fission. Starting from an electronic model Hamiltonian, we
      construct diabatic states in a manifold of single and double excitations with
      total singlet multiplicity and then develop a multilevel non-Markovian theory of
      dynamics for electronic populations in the presence of energy level fluctuations.
      Depending on the energy scales, energy gap fluctuations can either facilitate or
      hinder interconversion steps that lead to singlet fission. We critically assess
      the Markovian approximation that leads to golden rule rates and study the role of
      intramolecular solvation dynamics and electron transfer.

PMID- 22587485
TI  - Effects of neuromuscular electrical stimulation, laser therapy and LED therapy on
      the masticatory system and the impact on sleep variables in cerebral palsy
      patients: a randomized, five arms clinical trial.
AB  - BACKGROUND: Few studies demonstrate effectiveness of therapies for oral
      rehabilitation of patients with cerebral palsy (CP), given the difficulties in
      chewing, swallowing and speech, besides the intellectual, sensory and social
      limitations. Due to upper airway obstruction, they are also vulnerable to sleep
      disorders. This study aims to assess the sleep variables, through
      polysomnography, and masticatory dynamics, using electromiography, before and
      after neuromuscular electrical stimulation, associated or not with low power
      laser (Gallium Arsenide- Aluminun, =780 nm) and LED (= 660 nm) irradiation in CP
      patients. METHODS/DESIGN: 50 patients with CP, both gender, aged between 19 and
      60 years will be enrolled in this study. The inclusion criteria are: voluntary
      participation, patient with hemiparesis, quadriparesis or diparetic CP, with
      ability to understand and respond to verbal commands. The exclusion criteria are:
      patients undergoing/underwent orthodontic, functional maxillary orthopedic or
      botulinum toxin treatment. Polysomnographic and surface electromyographic exams
      on masseter, temporalis and suprahyoid will be carry out in all sample.
      Questionnaire assessing oral characteristics will be applied. The sample will be
      divided into 5 treatment groups: Group 1: neuromuscular electrical stimulation;
      Group 2: laser therapy; Group 3: LED therapy; Group 4: neuromuscular electrical
      stimulation and laser therapy and Group 5: neuromuscular electrical stimulation
      and LED therapy. All patients will be treated during 8 consecutive weeks. After
      treatment, polysomnographic and electromiographic exams will be collected again.
      DISCUSSION: This paper describes a five arm clinical trial assessing the
      examination of sleep quality and masticatory function in patients with CP under
      non-invasive therapies. TRIAL REGISTRATION: The protocol for this study is
      registered with the Brazilian Registry of Clinical Trials - ReBEC RBR-994XFS.

PMID- 22587488
TI  - How occupational health care professionals experience evidence-based guidelines
      in Finland: a qualitative study.
AB  - AIMS AND OBJECTIVES: Evidence-based guidelines are currently the most relevant
      source of information in practice. The adherence to and use of guidelines is
      often influenced by attitudes towards the guidelines themselves, which have not
      been sufficiently explored in occupational health. This study examines the
      attitude of Finnish occupational nurses' and doctors' attitudes towards evidence
      based guidelines. METHODS: Ten occupational doctors and eight occupational nurses
      were interviewed in Southern Finland on their attitudes towards evidence-based
      guidelines in 2009. RESULTS: The nurses were not very familiar with the concept
      of evidence-based medicine. Rather, they used recommendations developed in their
      workplace or by their employer. The evidence base of these recommendations was
      not clear. The doctors considered the evidence-based guidelines reliable and
      practical, but did not always act according to them. Participants felt that they
      did not have time to check guidelines during their working hours. Participants
      wished for clearer, shorter guidelines on occupational health care topics, which
      would help in their practical daily work and clarify roles in teamwork.
      CONCLUSIONS: Based on these positive attitudes, the use of guidelines may be more
      common than it seems. The viewpoints of all occupational health professional
      groups should be taken into account in guideline development, particularly on the
      availability and usability of the guidelines.

PMID- 22587489
TI  - Ablation of atrioventricular nodal reentrant tachycardia using the superior
      approach in a patient with IVC interruption.

PMID- 22587490
TI  - Non-equidistant scanning approach for millimetre-sized SPM measurements.
AB  - Long-range scanning probe microscope (SPM) measurements are usually extremely
      time consuming as many data need to be collected, and the microscope probe speed
      is limited. In this article, we present an adaptive measurement method for a
      large-area SPM. In contrast to the typically used line by line scanning with
      constant pixel spacing, we use an algorithm based on several levels of local
      refinement in order to minimize the amount of information that would be useless
      in the data processing phase. The data obtained from the measurement are in
      general formed by xyz data sets that are triangulated back with a desired local
      resolution. This enables storing more relevant information from a single
      measurement as the data are interpolated and regularized in the data processing
      phase instead of during the measurement. In this article, we also discuss the
      influence of thermal drifts on the measured data and compare the presented
      algorithm to the standard matrix-based measuring approach.

PMID- 22587491
TI  - The novel marker LTBP2 predicts all-cause and pulmonary death in patients with
      acute dyspnoea.
AB  - The risk stratification in patients presenting with acute dyspnoea remains a
      challenge. We therefore conducted a prospective, observational cohort study
      enrolling 292 patients presenting to the emergency department with acute
      dyspnoea. A proteomic approach for antibody-free targeted protein quantification
      based on high-end MS was used to measure LTBP2 [latent TGF (transforming growth
      factor)-binding protein 2] levels. Final diagnosis and death during follow-up
      were adjudicated blinded to LTBP2 levels. AHF (acute heart failure) was the final
      diagnosis in 54% of patients. In both AHF (P<0.001) and non-AHF (P=0.015)
      patients, LTBP2 levels at presentation were significantly higher in non-survivors
      compared with survivors with differences on median levels being 2.2- and 1.5-fold
      respectively. When assessing the cause of death, LTBP2 levels were significantly
      higher in patients dying from pulmonary causes (P=0.0005). Overall, LTBP2
      powerfully predicted early pulmonary death {AUC (area under the curve), 0.95 [95%
      CI (confidence interval), 0.91-0.98]}. In ROC (receiver operating characteristic)
      curve analyses for the prediction of 1-year mortality LTBP2 achieved an AUC of
      0.77 (95% CI, 0.71-0.84); comparable with the predictive potential of NT-proBNP
      [N-terminal pro-B-type natriuruetic peptide; 0.77 (95% CI, 0.72-0.82)].
      Importantly, the predictive potential of LTBP2 persisted in patients with AHF as
      the cause of dypnea (AUC 0.78) and was independent of renal dysfunction (AUC
      0.77). In a multivariate Cox regression analysis, LTBP2 was the strongest
      independent predictor of death [HR (hazard ratio), 3.76 (95% CI, 2.13-6.64);
      P<0.0001]. In conclusion, plasma levels of LTBP2 present a novel and powerful
      predictor of all-cause mortality, and particularly pulmonary death. Cause
      specific prediction of death would enable targeted prevention, e.g. with pre
      emptive antibiotic therapy.

PMID- 22587492
TI  - 18F-FDG PET/CT in patients with amyloid light-chain amyloidosis: case-series and
      literature review.
AB  - OBJECTIVES: To describe FDG-PET/CT in amyloid light-chain (AL) amyloidosis.
      METHODS: We describe a French multicenter study which included patients with AL
      amyloidosis who had undergone a FDG-PET/CT during follow-up. RESULTS: Ten
      patients with AL amyloidosis (median age 62 years [59-85]) were analyzed. AL
      amyloidosis was of lambda-type in 7/10 cases (70%) and localized amyloidosis in
      4/10 cases (40%). AL amyloidosis was primary in 7/10 (70%) cases and associated
      with Waldenstrom's macroglobulinemia (n = 2) and plasmocytoma (n = 1) in the
      remaining cases. Median delay between diagnosis and PET was 1 month [0-51]. PET
      was positive in seven (70%) patients and showed a median FDG SUV of 6.5 [ 4-15 ].
      FDG uptakes with positive PET were localized in seven patients, namely in the
      nasopharynx (n = 3), bronchopulmonary (n = 2), duodenal, cutaneous, bone, joint
      and muscular areas (n = 1, each). FDG uptakes on PET were concordant with the
      known organ impairment in 6/7 cases (86%) and showed unknown nasopharyngeal and
      mesenteric localization in one case each. PET was negative in the patient with
      cardiac amyloidosis and two patients with pulmonary amyloidosis. CONCLUSION: High
      FDG uptake may be present in patients with AL amyloidosis, however prospective
      studies are needed in order to determine the place of FDG PET in AL amyloidosis.

PMID- 22587493
TI  - Nematocidal effects of natural phytoregulators jasmonic acid and methyl-jasmonate
      against Pratylenchus zeae and Helicotylenchus spp.
AB  - The aim of this study was to evaluate the nematocidal effects of natural
      phytoregulators jasmonic acid (JA) and methyl-jasmonate (MJ) against plant
      parasitic nematodes Pratylenchus zeae (Graham) (Pratylenchidae) and
      Helicotylenchus spp. (Hoplolaimidae). Both JA and MJ promoted elevated
      percentages of mortality in P. zeae and Helicotylenchus spp. after 12 and 24 h of
      nematodes exposition at different concentrations of jasmonates. Considering the
      potential use of jasmonates as biofertiliser added now for their nematocidal
      effects, our results are of relevance in terms of biotechnological application.

PMID- 22587494
TI  - Depression and diabetes in India: perspectives and recommendations.
AB  - As diabetes prevalence shifts from affluent to lower-income groups in India,
      focus on depression in diabetes will become essential. This paper describes four
      perspectives through which depression and diabetes should be understood in the
      Indian context. We consider (1) how rapid socio-economic and demographic changes
      contribute to increased co-occurring diabetes and depression; (2) how social,
      cultural and economic factors in the Indian context contribute to depression and
      therefore play an important role in diabetes care; (3) biological and behavioural
      pathways between depression and diabetes; and (4) the role of health systems in
      depression, diabetes and their overlap. We conclude with recommendations for
      future research and policy on this topic in India.

PMID- 22587496
TI  - Transcription profiling in environmental diagnostics: health assessments in
      Columbia River basin steelhead (Oncorhynchus mykiss).
AB  - The health condition of out-migrating juvenile salmonids can influence migration
      success. Physical damage, pathogenic infection, contaminant exposure, and immune
      system status can affect survival probability. The present study is part of a
      wider investigation of out-migration success in juvenile steelhead (Oncorhynchus
      mykiss) and focuses on the application of molecular profiling to assess sublethal
      effects of environmental stressors in field-collected fish. We used a suite of
      genes in O. mykiss to specifically assess responses that could be directly
      related to steelhead health condition during out-migration. These biomarkers were
      used on juvenile steelhead captured in the Snake River, a tributary of the
      Columbia River, in Washington, USA, and were applied on gill and anterior head
      kidney tissue to assess immune system responses, pathogen-defense (NRAMP, Mx,
      CXC), general stress (HSP70), metal-binding (metallothionein-A), and xenobiotic
      metabolism (Cyp1a1) utilizing quantitative polymerase chain reaction (PCR)
      technology. Upon capture, fish were ranked according to visual external physical
      conditions into good, fair, poor, and bad categories; gills and kidney tissues
      were then dissected and preserved for gene analyses. Transcription responses were
      tissue-specific for gill and anterior head kidney with less significant responses
      in gill tissue than in kidney. Significant differences between the condition
      ranks were attributed to NRAMP, MX, CXC, and Cyp1a1 responses. Gene profiling
      correlated gene expression with pathogen presence, and results indicated that
      gene profiling can be a useful tool for identifying specific pathogen types
      responsible for disease. Principal component analysis (PCA) further correlated
      these responses with specific health condition categories, strongly
      differentiating good, poor, and bad condition ranks. We conclude that molecular
      profiling is an informative and useful tool that could be applied to indicate and
      monitor numerous population-level parameters of management interest.

PMID- 22587495
TI  - Quantification of differential ErbB1 and ErbB2 cell surface expression and
      spatial nanoclustering through plasmon coupling.
AB  - Cell surface receptors play ubiquitous roles in cell signaling and communication
      and their expression levels are important biomarkers for many diseases.
      Expression levels are, however, only one factor that determines the physiological
      activity of a receptor. For some surface receptors, their distribution on the
      cell surface, especially their clustering, provides additional mechanisms for
      regulation. To access this spatial information robust assays are required that
      provide detailed insight into the organization of cell surface receptors on
      nanometer length scales. In this manuscript, we demonstrate through combination
      of scattering spectroscopy, electron microscopy, and generalized multiple
      particle Mie theory (GMT) simulations that the density- and morphology-dependent
      spectral response of Au nanoparticle (NP) immunolabels bound to the epidermal
      growth factor receptors ErbB1 and ErbB2 encodes quantitative information of both
      the cell surface expression and spatial clustering of the two receptors in
      different unliganded in vitro cancer cell lines (SKBR3, MCF7, A431). A systematic
      characterization of the collective spectral responses of NPs targeted at ErbB1
      and ErbB2 at various NP concentrations indicates differences in the large-scale
      organization of ErbB1 and ErbB2 in cell lines that overexpress these receptors.
      Validation experiments in the scanning electron microscope (SEM) confirm that NPs
      targeted at ErbB1 on A431 are more strongly clustered than NPs bound to ErbB2 on
      SKBR3 or MCF7 at overall comparable NP surface densities. This finding is
      consistent with the existence of larger receptor clusters for ErbB1 than for
      ErbB2 in the plasma membranes of the respective cells.

PMID- 22587497
TI  - Transitions.

PMID- 22587499
TI  - A 14-year-old boy with vomiting.

PMID- 22587500
TI  - An unexpected cause of infantile failure to thrive.

PMID- 22587501
TI  - Vesicopustular eruption in a neonate.

PMID- 22587502
TI  - Transition to adult care.

PMID- 22587503
TI  - Pediatric assessment and management of concussions.

PMID- 22587504
TI  - Exclusion of mildly ill children from childcare.

PMID- 22587505
TI  - 10 useful apps for everyday pediatric use.

PMID- 22587506
TI  - A conversation with Tomisaku Kawasaki, MD. Interviewed by Stanford T. Shulman.

PMID- 22587507
TI  - A primary care quality improvement approach to health care transition.

PMID- 22587508
TI  - Transition of care for young adults with type 1 and 2 diabetes.

PMID- 22587509
TI  - Adolescent rheumatology transition care in the UK.

PMID- 22587510
TI  - The management of gestational diabetes.
AB  - The incidence of gestational diabetes is increasing, with higher obesity in the
      pregnant population, lifestyle changes and migration thought to underlie this.
      Recent large studies, such as the MiG, HAPO and ACHOIS trials, have furthered our
      understanding of both the implications of the disease and the management options
      available. Previous CEMACH (Confidential Enquiries into Maternal and Child
      Health) studies of diabetes in pregnancy have shown a significant proportion of
      patients receiving sub-optimal care. We aim to summarise the current standard of
      management strategies in pregnancy, whilst acknowledging controversies and
      limitations in the existing evidence. Antenatal management involves service
      organisation to provide multi-disciplinary team reviews to address glycaemic
      control, fetal monitoring and associated conditions such as obesity and
      hypertensive disorders of pregnancy. The use of diet, exercise, oral
      hypoglycaemic agents and insulins will be discussed, along with specific
      considerations for the management of preterm labour and administration of
      corticosteroids for fetal lung maturity. The timing and management of labour,
      including mechanisms of delivery, will be covered, including neonatal
      considerations and the use of breast feeding. Finally, a discussion of
      appropriate post delivery care will consider the prevention of, and screening
      for, the development of type 2 diabetes.

PMID- 22587511
TI  - Genetic association studies in diabetic nephropathy.
AB  - Clinical observations and epidemiological studies have shown that there is
      familial aggregation of diabetic nephropathy in many ethnic groups, indicating
      the strong contribution of inherited factors in the development of diabetic
      nephropathy. Identification of the genes involved in the pathogenesis of diabetic
      nephropathy may provide better knowledge of its pathophysiology and future
      therapies. To search for the genes involved in susceptibility, resistance or
      progression to diabetic nephropathy, candidate gene population association,
      family-based association and genome wide association studies have been widely
      used. This article reviews genetic polymorphisms, summarizes the data from
      genetic association studies of diabetic nephropathy in both type 1 and type 2
      diabetes, and discusses about the future genetic analyses in the complex
      diseases.

PMID- 22587512
TI  - Subthreshold diode micropulse laser photocoagulation (SDM) as invisible retinal
      phototherapy for diabetic macular edema: a review.
AB  - PURPOSE: To present the state-of-the-art of subthreshold diode laser micropulse
      photocoagulation (SDM) as invisible retinal phototherapy for diabetic macular
      edema (DME). METHOD: To review the role and evolution of retinal laser treatment
      for DME. RESULTS: Thermal laser retinal photocoagulation has been the cornerstone
      of treatment for diabetic macular edema for over four decades. Throughout, laser
      induced retinal damage produced by conventional photocoagulation has been
      universally accepted as necessary to produce a therapeutic benefit, despite the
      inherent risks, adverse effects and limitations of thermally destructive
      treatment. Recently, SDM, performed as invisible retinal phototherapy for DME,
      has been found to be effective in the absence of any retinal damage or adverse
      effect, fundamentally altering our understanding of laser treatment for retinal
      disease. SUMMARY: The discovery of clinically effective and harmless SDM
      treatment for DME offers exciting new information that will improve our
      understanding of laser treatment for retinal disease, expand treatment
      indications, and improve patient outcomes.

PMID- 22587513
TI  - FGF21: The center of a transcriptional nexus in metabolic regulation.
AB  - Fibroblast growth factor 21 (FGF21) is emerging as a key regulator of energy
      homeostasis and presents a novel target for the development of therapies for the
      treatment of diabetes, cardiovascular disease and obesity. Recent publications
      have demonstrated that FGF21 resides downstream of a complex network of
      transcriptional regulators which modulate its expression in response to a wide
      array of physiological stimuli or pharmacologic agents. The manner in which these
      mechanisms are integrated to regulate FGF21 transcription, production and
      subsequent secretion is poorly understood. While FGF21 is detected in many
      metabolically active tissues and is regulated by several of the known
      transcription factors involved in metabolic control little is known about how
      these pathways are integrated. In this review, we discuss the data presented to
      date on regulation of FGF21 by a wide array of transcription factors and explore
      how it relates to metabolic regulation in vivo.

PMID- 22587514
TI  - Glucagon and cyclic AMP: time to turn the page?
AB  - It is well established that glucagon can stimulate adipose lipolysis, myocardial
      contractility, and hepatic glucose output by activating a GPCR and adenylate
      cyclase (AC) and increasing cAMP production. It is also widely reported that
      activation of AC in all three tissues requires pharmacological levels of the
      hormone, exceeding 0.1 nM. Extensive evidence is presented here supporting the
      view that cAMP does not mediate metabolic actions of glucagon on adipose, heart,
      or liver in vivo. Only pharmacological levels stimulate AC, adipose lipolysis, or
      cardiac contractility. Physiological concentrations of glucagon (below 0.1 nM)
      duplicate metabolic effects of insulin on the heart by activating a PI3K
      dependent signal without stimulating AC. In the liver, glucagon can enhance
      gluconeogenesis and glucose output - by increasing the expression of PEPCK or
      inhibiting the activity of PK - at pharmacological concentrations by activating
      AC coupled to a low-affinity GPCR, but also at physiological concentrations by
      activating a high affinity receptor without generating cAMP. Plausible AC/cAMP
      independent signals mediating the increase in gluconeogenesis include p38 MAPK
      (PEPCK expression) and IP3/DAG/Ca(2+) (PK activity). None of glucagon's
      physiological effects can be explained by activation of spare receptors or
      amplification of the AC/cAMP signal. In a new model proposed here, glucagon
      antagonizes insulin on the liver but mimics insulin on the heart without
      activating AC. Confirmation of the model would have broad implications,
      applicable not only to the general field of metabolic endocrinology but also to
      the specific role of glucagon in the pathogenesis and treatment of diabetes.

PMID- 22587515
TI  - Corneal changes in diabetes mellitus.
AB  - Diabetes mellitus is a major disease worldwide, and the prevalence of diabetes
      has risen significantly in the past several decades. Although one of the major
      complications of diabetic eyes is diabetic retinopathy (DR), corneal diseases can
      not only develop in diabetic patients but are also difficult to manage. Diabetic
      neurotrophic keratopathy is a component of diabetic polyneuropathy and is
      recognized to be the cause of the morbidity of the cornea in diabetic patients.
      In addition, corneal endothelial cell damage can cause disturbances in the
      management of proliferative DR before and after surgeries because of endothelial
      decompensation with bullous keratopathy. However, there have been only a limited
      number of studies that have focused on the importance of corneal diseases in
      diabetic patients. This review describes the pathophysiological roles of
      different factors that have been found to be causative factors of diabetic
      corneal keratopathy and endothelial cell dysfunction in diabetic patients. In
      addition, the clinical features of the corneal changes in diabetic patients and
      recent studies related to the development of therapies for the management of
      corneal diseases are presented.

PMID- 22587516
TI  - Islets from rats and pigs transgenic for photogenic proteins.
AB  - Translational research is necessary for the development of efficient experimental
      animal models that can be used to develop innovative medical treatments, such as
      improvements in organ or tissue transplantation. We have developed animal models
      that produce photogenic proteins in their islet cells: rats models expressing the
      gene for luciferase or green fluorescent protein (GFP), and pig models expressing
      the gene for GFP or Kusabira-Orange. We also developed methods for preserving
      isolated islets in culture and showed that the fluorescence of the islets remains
      at usable levels for at least seven days. These models will enable transplanted
      islets to be visualized without the need for chemical reactions, and will be
      useful for research on the biology of islets as well as for the development of
      new transplantation methods.

PMID- 22587518
TI  - Antifungal activity of Andrographis paniculata extracts and active principles
      against skin pathogenic fungal strains in vitro.
AB  - CONTEXT: Andrographis paniculata Nees. (Acanthaceae) is an annual herbaceous
      plant widely cultivated in southern Asia, China, and Europe. It is used in the
      treatment of skin infections in India, China, and Malaysia by folk medicine
      practitioners. OBJECTIVE: Antifungal activity of the whole plant extracts and
      isolation of active principles from A. paniculata were investigated. MATERIALS
      AND METHODS: Dichloromethane (DCM) and methanol (MEOH) extracts of A. paniculata
      whole plant were screened for their antifungal potential using broth
      microdilution method in vitro against seven pathogenic fungal species responsible
      for skin infections. Active principles were detected through bioguided assays and
      isolated using chromatography techniques. Structures of compounds were elucidated
      through spectroscopy techniques and comparisons were made with previously
      reported data for similar compounds. RESULTS: DCM extract revealed lowest minimum
      inhibitory concentration (MIC) value (100 MUg/mL) against Microsporum canis,
      Candida albicans, and Candida tropicalis, whereas MEOH extract revealed lowest
      MIC (150 ug/mL) against C. tropicalis and Aspergillus niger. DCM extract showed
      lowest minimum fungicidal concentration (MFC) value (250 ug/mL) against M. canis,
      C. albicans, C. tropicalis and A. niger, whereas MEOH extract showed lowest MFC
      (250 ug/mL) against Trichophyton mentagrophytes, Trichophyton rubrum, M. canis,
      C. albicans, C. tropicalis and A. niger. Bioassay guided isolation from DCM and
      MEOH extract afforded 3-O-beta-d-glucosyl-14-deoxyandrographiside, 14
      deoxyandrographolide, and 14-deoxy-11,12-didehydroandrographolide as antifungal
      compounds. The lowest MIC (50 ug/mL) and MFC (50 ug/mL) was exerted by 14
      deoxyandrographolide on M. canis. DISCUSSION AND CONCLUSION: This is first report
      on the isolation of antifungal substances through bioassay-guided assay from A.
      paniculata. Our finding justifies the use of A. paniculata in folk medicines for
      the treatment of fungal skin infections.

PMID- 22587520
TI  - Special focus--Antibody-mediated rejection. Guest editorial.

PMID- 22587517
TI  - The good and bad effects of cysteine S-nitrosylation and tyrosine nitration upon
      insulin exocytosis: a balancing act.
AB  - As understanding of the mechanisms driving and regulating insulin secretion from
      pancreatic beta cells grows, there is increasing and compelling evidence that
      nitric oxide (*NO) and other closely-related reactive nitrogen species (RNS) play
      important roles in this exocytic process. *NO and associated RNS, in particular
      peroxynitrite, possess the capability to effect signals across both intracellular
      and extracellular compartments in rapid fashion, affording extraordinary
      signaling potential. It is well established that nitric oxide signals through
      activation of guanylate cyclase-mediated production of cyclic GMP. The intricate
      intracellular redox environment, however, lends credence to the possibility that
      *NO and peroxynitrite could interact with a wider variety of biological targets,
      with two leading mechanisms involving 1) Snitrosylation of cysteine, and 2)
      nitration of tyrosine residues comprised within a variety of proteins. Efforts
      aimed at delineating the specific roles of *NO and peroxynitrite in regulated
      insulin secretion indicate that a highly-complex and nuanced system exists, with
      evidence that *NO and peroxynitrite can contribute in both positive and negative
      regulatory ways in beta cells. Furthermore, the ultimate biochemical outcome
      within beta cells, whether to compensate and recover from a given stress, or not,
      is likely a summation of contributory signals and redox status. Such seeming
      regulatory dichotomy provides ample opportunity for these mechanisms to serve
      both physiological and pathophysiologic roles in onset and progression of
      diabetes. This review focuses attention upon recent accumulating evidence
      pointing to roles for nitric oxide induced post-translational modifications in
      the normal regulation as well as the dysfunction of beta cell insulin exocytosis.

PMID- 22587519
TI  - (Z)-1-aryl-3-arylamino-2-propen-1-ones, highly active stimulators of tubulin
      polymerization: synthesis, structure-activity relationship (SAR), tubulin
      polymerization, and cell growth inhibition studies.
AB  - Tubulin, the major structural component of microtubules, is a target for the
      development of anticancer agents. A series of (Z)-1-aryl-3-arylamino-2-propen-1
      one (10) were synthesized and evaluated for antiproliferative activity in cell
      based assay. The most active compound (Z)-1-(2-bromo-3,4,5-trimethoxyphenyl)-3-(3
      hydroxy-4-methoxyphenylamino)prop-2-en-1-one (10ae) was tested in 20 tumor cell
      lines including multidrug resistant phenotype and was found to induce apoptosis
      in all these cell lines with similar GI(50) values. Flow cytometry studies showed
      that 10ae arrested the cells in G2/M phase of cell cycle. In addition to G2/M
      block, these compounds caused microtubule stabilization like paclitaxel and
      induced apoptosis via activation of the caspase family. The observations made in
      this investigation demonstrate that (Z)-1-Aryl-3-arylamino-2-propen-1-one (10)
      represents a new class of microtubule-stabilizing agents.

PMID- 22587521
TI  - Detection and clinical relevance of donor specific HLA antibodies: a matter of
      debate.
AB  - The introduction of new sensitive assays for the detection of HLA antibodies on
      basis of their binding to isolated HLA molecules has got an enormous impact on
      the decision-making process with respect to donor selection for sensitized
      patients. In the past, when only complement-dependent cytotoxicity was used as a
      tool to define HLA alloantibodies, the presence of donor specific antibodies
      (DSA) before transplantation was considered a contraindication for renal
      transplantation with that donor. The interpretation of the current DSA results is
      far more difficult and leads to a lot of discussions and controversy. The
      problems associated with the use of solid phase assays for clinical decision
      making and possible solutions are discussed.

PMID- 22587522
TI  - Prevention of antibody-mediated kidney transplant rejection.
AB  - There is increasing evidence that antibody-mediated rejection is the major cause
      of late kidney graft failure. Prevention of antibody-mediated allograft damage
      has therefore become an important issue in kidney transplantation. Such
      prevention starts already before transplantation with the avoidance of
      sensitizing events. When a patient is already sensitized, precise
      characterization of alloantibodies and exact HLA typing of the donor at the time
      of transplantation are mandatory. To ensure timely and successful transplantation
      of highly sensitized patients, desensitization, and inclusion in special programs
      such as the Eurotransplant Acceptable Mismatch Program should be considered.
      After transplantation, close monitoring of kidney function, testing for the de
      novo development or changing characteristics of alloantibodies, and attention to
      non-adherence to immunosuppression is obligatory. In the current overview, we
      discuss the currently available measures for the prevention of antibody-mediated
      kidney graft rejection.

PMID- 22587523
TI  - Negative electron affinities from DFT: influence of asymptotic exchange
      correlation potential and effective homogeneity under density scaling.
AB  - The influence of the asymptotic exchange-correlation potential and density
      scaling homogeneity on negative electron affinities determined using the approach
      of Tozer and De Proft [J. Phys. Chem. A2005, 109, 8923] is investigated.
      Application of an asymptotic correction to the potential improves the accuracy
      for several of the systems with the most negative affinities, reflecting their
      diffuse lowest unoccupied orbitals. For systems with modest affinities, it
      reduces the accuracy marginally. Enforcing a near-exact effective homogeneity
      through a simple shift in the potential leads to improved correlation with
      experimental values but significantly overestimated affinities. Optimal effective
      homogeneities are therefore determined, and a simple scheme is proposed for
      enforcing an average optimal value. Application of the scheme to a series of
      organic molecules maintains the excellent correlation with the experimental
      values while significantly reducing the absolute errors.

PMID- 22587525
TI  - Retraction: Role of senescence and mitotic catastrophe in cancer therapy.

PMID- 22587524
TI  - A difficult conversation? The views and experiences of parents and professionals
      on the consent process for perinatal postmortem after stillbirth.
AB  - OBJECTIVE: To describe the experiences, knowledge and views of both parents and
      professionals regarding the consent process for perinatal postmortem. DESIGN:
      Internet-based survey. SETTING: Obstetricians, midwives and perinatal
      pathologists currently working in the UK. Parents who have experienced a
      stillbirth in the UK in the previous 10 years. SAMPLE: Obstetricians, midwives
      and perinatal pathologists registered with their professional bodies. Parents who
      accessed the Sands website or online forum. METHODS: Online self-completion
      questionnaire with both fixed-choice and open-ended questions. RESULTS: Responses
      were analysed from 2256 midwives, 354 obstetricians, 21 perinatal pathologists
      and 460 parents. The most common reason for parents to request postmortem
      examination was to find a cause for their baby's death; the prevention of
      stillbirths in others also ranked highly. Perinatal pathologists possessed
      greatest knowledge of the procedure and efficacy of postmortem, but were unlikely
      to meet bereaved parents. The majority of professionals and parents ranked
      emotional distress and a lengthy wait for results as barriers to consent. The
      majority of staff ranked workload, negative publicity, religion and cultural
      issues as important barriers, whereas most parents did not. Almost twice as many
      parents who declined postmortem examination later regretted their decision
      compared with those who accepted the offer (34.4 versus 17.4%). CONCLUSION:
      Emotional, practical and psychosocial issues can act as real or perceived
      barriers for staff and bereaved parents. Education is required for midwives and
      obstetricians, to increase their knowledge to ensure accurate counselling, with
      due regard for the highly individual responses of bereaved parents. The
      contribution of perinatal pathologists to staff education and parental decision
      making would be invaluable.

PMID- 22587526
TI  - The partitioned LASSO-patternsearch algorithm with application to gene expression
      data.
AB  - BACKGROUND: In systems biology, the task of reverse engineering gene pathways
      from data has been limited not just by the curse of dimensionality (the
      interaction space is huge) but also by systematic error in the data. The gene
      expression barcode reduces spurious association driven by batch effects and probe
      effects. The binary nature of the resulting expression calls lends itself
      perfectly to modern regularization approaches that thrive in high-dimensional
      settings. RESULTS: The Partitioned LASSO-Patternsearch algorithm is proposed to
      identify patterns of multiple dichotomous risk factors for outcomes of interest
      in genomic studies. A partitioning scheme is used to identify promising patterns
      by solving many LASSO-Patternsearch subproblems in parallel. All variables that
      survive this stage proceed to an aggregation stage where the most significant
      patterns are identified by solving a reduced LASSO-Patternsearch problem in just
      these variables. This approach was applied to genetic data sets with expression
      levels dichotomized by gene expression bar code. Most of the genes and second
      order interactions thus selected and are known to be related to the outcomes.
      CONCLUSIONS: We demonstrate with simulations and data analyses that the proposed
      method not only selects variables and patterns more accurately, but also provides
      smaller models with better prediction accuracy, in comparison to several
      alternative methodologies.

PMID- 22587527
TI  - Understanding surfactant/graphene interactions using a graphene field effect
      transistor: relating molecular structure to hysteresis and carrier mobility.
AB  - Manipulation of transport hysteresis on graphene transistors and understanding
      electron transfer between graphene and polar/ionic adsorbates are important for
      the development of graphene-based sensor devices and nonvolatile memory
      electronics. We have investigated the effects of commonly used surfactants for
      graphene dispersion in aqueous solution on transport characteristics of graphene
      transistors. The adsorbates are found to transfer electrons to graphene, scatter
      carrier transport, and induce additional electron-hole puddles when the graphene
      is on an SiO(2) substrate. We relate the change in transport characteristics to
      specific chemical properties of a series of anionic, cationic, and neutral
      surfactants using a modification of a self-consistent transport theory developed
      for graphene. To understand the effects of surfactant adsorbates trapped on
      either side of the graphene, suspended devices were fabricated. Strong hysteresis
      is observed only when both sides of the graphene were exposed to the surfactants,
      attributable to their function as charge traps. This work is the first to
      demonstrate the control of hysteresis, allowing us to eliminate it for sensor and
      device applications or to enhance it to potentially enable nonvolatile memory
      applications.

PMID- 22587529
TI  - New cell line development for antibody-producing Chinese hamster ovary cells
      using split green fluorescent protein.
AB  - BACKGROUND: The establishment of high producer is an important issue in Chinese
      hamster ovary (CHO) cell culture considering increased heterogeneity by the
      random integration of a transfected foreign gene and the altered position of the
      integrated gene. Fluorescence-activated cell sorting (FACS)-based cell line
      development is an efficient strategy for the selection of CHO cells in high
      therapeutic protein production. RESULTS: An internal ribosome entry site (IRES)
      was introduced for using two green fluorescence protein (GFP) fragments as a
      reporter to both antibody chains, the heavy chain and the light chain. The cells
      co-transfected with two GFP fragments showed the emission of green fluorescence
      by the reconstitution of split GFP. The FACS-sorted pool with GFP expression had
      a higher specific antibody productivity (q(Ab)) than that of the unsorted pool.
      The q(Ab) was highly correlated with the fluorescence intensity with a high
      correlation coefficient, evidenced from the analysis of median GFP and q(Ab) in
      individual selected clones. CONCLUSIONS: This study proved that the fragment
      complementation for split GFP could be an efficient indication for antibody
      production on the basis of high correlation of q(Ab) with reconstitution of GFP.
      Taken together, we developed an efficient FACS-based screening method for high
      antibody-producing CHO cells with the benefits of the split GFP system.

PMID- 22587530
TI  - Sildenafil for COPD: a randomized crossover trial.

PMID- 22587533
TI  - Clinician awareness of tetanus-diphtheria vaccination in trauma patients: a
      questionnaire study.
AB  - BACKGROUND: Most trauma patients visit the hospital via the emergency department.
      They are at high risk for tetanus infection because many trauma patients are
      wounded. Tetanus immunity in the Korean population has been revealed to be
      decreased in age groups over 20 years old. It is important for emergency
      physicians to vaccinate patients with the tetanus booster in wound management.
      METHODS: Questionnaires were sent to the directors of the emergency departments
      of resident training hospitals certified by the Korean Society of Emergency
      Medicine. RESULTS: Two thirds of the emergency department directors surveyed
      reported applying tetanus prophylaxis guidelines to more than 80% of wounded
      patients. However, about 45% of clinicians in the emergency departments
      considered giving less than half of the wounded patient tetanus booster
      vaccinations, and there were no distinct differences in tetanus booster
      vaccination rates among different age groups. Most emergency physicians are
      familiar with tetanus prophylaxis guidelines for wound management. However, more
      than half of the emergency department directors reported that the major reason
      for not considering tetanus-diphtheria vaccination was due to assumptions that
      patients already had tetanus immunity. CONCLUSION: Attitude changes should be
      encouraged among emergency physicians regarding tetanus prophylaxis. As emergency
      physicians are frequently confronted with patients that are at a high risk for
      tetanus infection in emergency situations, they need to be more informed
      regarding tetanus immunity epidemiology and encouraged to administer tetanus
      booster vaccines.

PMID- 22587534
TI  - Study of interaction between PEG carrier and three relevant drug molecules:
      piroxicam, paclitaxel, and hematoporphyrin.
AB  - Molecular dynamics simulation has been used to study the specific interactions
      between poly(ethylene glycol) (PEG) and three drug molecules for which PEG is
      used to aid delivery: paclitaxel and piroxicam, where PEG is a carrier agent, and
      hematoporphyrin, where PEG is covalently attached to form a "stealth shield".
      Simulating at physiological salt concentration, we found no evidence of any
      specific interaction between paclitaxel or piroxicam with PEG, but found a strong
      interaction for the case of hematoporphyrin. This interaction is lipophilic in
      nature, between the nonpolar (CH(2))(2) groups of the PEG and the porphin ring of
      the hematoporphyrin. This interaction was found to be strong enough that the PEG
      aggregated to the hematoporphyrin, independent of whether or not it was
      covalently bound. Interestingly, when the simulation was repeated in absence of
      salt we found evidence of this interaction being weakened. This led us to
      hypothesize a previously unforeseen mechanism: interaction with salt cations
      cause the PEG to coil around the salt ions, each ion binding to many PEG oxygens,
      increasing the exposure of the nonpolar ethylene groups, thus increasing the
      effective hydrophobicity of PEG. The Hydrophobic ethylene groups of the PEG
      chains adhere strongly to the hydrophobic porphin ring. Experiments involving
      absorption spectra measurements were conducted, and these results also indicated
      that presence of salt at physiological level increases the effective attractive
      interaction between PEG and hematoporphyrin. Taken together, our results
      demonstrate that while PEG, due to its solubility in both polar and nonpolar
      solvents, may act as a dissolution aid for paclitaxel and piroxicam, of the three
      drug molecules studied it will only have a protective role for the case of the
      hematoporphyrin.

PMID- 22587537
TI  - Upcoming New Feature in the Journal of Biomolecular Structure & Dynamics.

PMID- 22587539
TI  - Clinical information transfer and data capture in the acute myocardial infarction
      pathway: an observational study.
AB  - RATIONALE, AIMS AND OBJECTIVES: Acute myocardial infarctions (MIs) or heart
      attacks are the result of a complete or an incomplete occlusion of the lumen of
      the coronary artery with a thrombus. Prompt diagnosis and early coronary
      intervention results in maximum myocardial salvage, hence time to treat is of the
      essence. Adequate, accurate and complete information is vital during the early
      stages of admission of an MI patient and can impact significantly on the quality
      and safety of patient care. This study aimed to record how clinical information
      between different clinical teams during the journey of a patient in the MI care
      pathway is captured and to review the flow of information within this care
      pathway. METHOD: A prospective, descriptive, structured observational study to
      assess (i) current clinical information systems (CIS) utilization and (ii) real
      time information availability within an acute cardiac care setting was carried
      out. Completeness and availability of patient information capture across four key
      stages of the MI care pathway were assessed prospectively. RESULTS: Thirteen
      separate information systems were utilized during the four phases of the MI
      pathway. Observations revealed fragmented CIS utilization, with users accessing
      an average of six systems to gain a complete set of patient information. Data
      capture was found to vary between each pathway stage and in both patient cohort
      risk groupings. The highest level of information completeness (100%) was observed
      only in the discharge stage of the MI care pathway. The lowest level of
      information completeness (58%) was observed in the admission stage. CONCLUSION:
      The study highlights fragmentation, CIS duplication, and discrepancies in the
      current clinical information capture and data transfer across the MI care pathway
      in an acute cardiac care setting. The development of an integrated and user
      friendly electronic data capture and transfer system would reduce duplication and
      would facilitate efficient and complete information provision at the point of
      care.

PMID- 22587540
TI  - A scientific nutrition strategy improves time trial performance by ~6% when
      compared with a self-chosen nutrition strategy in trained cyclists: a randomized
      cross-over study.
AB  - We investigated whether an athlete's self-chosen nutrition strategy (A), compared
      with a scientifically determined one (S), led to an improved endurance
      performance in a laboratory time trial after an endurance exercise. S consisted
      of about 1000 mL.h(-1) fluid, in portions of 250 mL every 15 min, 0.5 g sodium.L(
      1), 60 g glucose.h(-1), 30 g fructose.h(-1), and 5 mg caffeine.kg body mass(-1).
      Eighteen endurance-trained cyclists (16 male; 2 female) were tested using a
      randomized crossover-design at intervals of 2 weeks, following either A or S.
      After a warm-up, a maximal oxygen uptake test was performed. Following a 30-min
      break, a 2.5-h endurance exercise on a bicycle ergometer was carried out at 70%
      maximal oxygen uptake. After 5 min of rest, a time trial of 64.37 km (40 miles)
      was completed. The ingested nutrition was recorded every 15 min. In S, the
      athletes completed the time trial faster (128 vs. 136 min; p <= 0.001) and with a
      significantly higher power output (212 vs. 184 W; p <= 0.001). The intake of
      fluid, energy (carbohydrate-, mono-, and disaccharide), and sodium was
      significantly higher in S compared with A (p <= 0.001) during the endurance
      exercise. In the time trial, only sodium intake was significantly higher in S (p
      <= 0.001). We concluded that a time trial performance after a 2.5-h endurance
      exercise in a laboratory setting was significantly improved following a
      scientific nutrition strategy.

PMID- 22587541
TI  - Dermoscopy: an aid to the detection of amelanotic cutaneous melanoma metastases.
AB  - BACKGROUND: The recognition of amelanotic cutaneous melanoma metastases (ACMM)
      remains a diagnostic challenge. OBJECTIVES: To describe and analyze the clinical
      and dermoscopic characteristics of ACMM. PATIENTS AND METHODS: Cases of ACMM were
      retrospectively selected from the image databases of three dermatology centers.
      The clinical and dermoscopic images were combined into one database for analysis.
      RESULTS: Forty-seven ACMM were observed in 18 patients. All lesions were
      erythematous, symmetric, dome-shaped papules or nodules appearing an average of
      17 months after the diagnosis of the primary melanoma. ACMM presented as clinical
      outliers or as nonspecific papules found by palpation of the skin. The
      predominant dermoscopic feature was the presence of vascular structures,
      including serpentine (45%), glomerular (30%), irregular hairpin (23%) and
      corkscres-like vessels (19%). A few lesions also revealed crystalline (or shiny
      white lines) when viewed using polarized dermoscopy. CONCLUSION: ACMM should be
      considered in the differential diagnosis of new or persistent skin-colored or
      pink papules in patients with a previous history of invasive melanoma, especially
      if the lesions reveal atypical vessels under dermoscopy. The presence of
      crystalline structures may be another clue for the detection of some ACMM.

PMID- 22587542
TI  - Enhanced magnetic-field-induced optical properties of nanostructured magnetic
      fluids by doping nematic liquid crystals.
AB  - Ferronematic materials composed of 4-cyano-4'-pentylbiphenyl nematic liquid
      crystal and oil-based Fe3O4 magnetic fluid were prepared using ultrasonic
      agitation. The birefringence (Deltan) and figure of merit of optical properties
      (Q = Deltan/alpha, where alpha is the extinction coefficient) of pure magnetic
      fluids and the as-prepared ferronematic materials were examined and compared. The
      figure of merit of optical properties weighs the birefringence and extinction of
      the materials and is more appropriate to evaluate their optical properties.
      Similar magnetic-field- and magnetic-particle-concentration-dependent properties
      of birefringence and figure of merit of optical properties were obtained for the
      pure magnetic fluids and the ferronematic materials. For the ferronematic
      materials, the values of Q increase with the volume fractions of nematic liquid
      crystal under certain fixed field strength and are larger than those of their
      corresponding pure magnetic fluids at high field region. In addition, the
      enhancement of Q value increases monotonously with the magnetic field and becomes
      remarkable when the applied magnetic field is beyond 50 mT. The maximum relative
      enhanced value of QR exceeds 6.8% in our experiments. The results of this work
      may conduce to extend the pragmatic applications of nanostructured magnetic
      fluids in optical field.

PMID- 22587543
TI  - Combined QSAR studies of inhibitor properties of O-phosphorylated oximes toward
      serine esterases involved in neurotoxicity, drug metabolism and Alzheimer's
      disease.
AB  - Oxime reactivation of serine esterases (EOHs) inhibited by organophosphorus (OP)
      compounds can produce O-phosphorylated oximes (POXs). Such oxime derivatives are
      of interest, because some of them can have greater anti-EOH potencies than the OP
      inhibitors from which they were derived. Accordingly, inhibitor properties of 58
      POXs against four EOHs, along with pair-wise selectivities between them, have
      been analysed using different QSAR approaches. EOHs (with their abbreviations and
      consequences of inhibition in parentheses) comprised acetylcholinesterase (AChE:
      acute neurotoxicity; cognition enhancement), butyrylcholinesterase (BChE:
      inhibition of drug metabolism or stoichiometric scavenging of EOH inhibitors;
      cognition enhancement), carboxylesterase (CaE: inhibition of drug metabolism or
      stoichiometric scavenging of EOH inhibitors), and neuropathy target esterase
      (NTE: delayed neurotoxicity). QSAR techniques encompassed linear regression and
      backpropagation neural networks in conjunction with fragmental descriptors
      containing labelled atoms, Molecular Field Topology Analysis (MFTA), Comparative
      Molecular Similarity Index Analysis (CoMSIA), and molecular modelling. All
      methods provided mostly consistent and complementary information, and they
      revealed structural features controlling the 'esterase profiles', i.e. patterns
      of anti-EOH activities and selectivities of the compounds of interest. In
      addition, MFTA models were used to design a library of compounds having a
      cognition-enhancement esterase profile suitable for potential application to the
      treatment of Alzheimer's disease.

PMID- 22587544
TI  - Conceptualization in the pigeon: What do we know?

PMID- 22587545
TI  - Acculturation of Greek Americans: Change and continuity in cognitive schemas
      guiding intimate relationships.
AB  - The study compares Greek Americans to Greeks and to third-generation white
      Americans in their endorsement of two cognitive schemas guiding intimate
      relationships. Greek Americans were more rejecting of low self-disclosure in
      intimate relationships than were Greeks but did not differ from them on how
      strongly they advocated sacrificing the self for one's partner. By contrast,
      Greek Americans did not differ from Americans in their rejection of low self
      disclosure and more strongly endorsed self-sacrifice in intimate relationships
      than did Americans. These findings were interpreted as indicating that Greek
      Americans have acculturated to a more individualistic orientation in terms of
      self-disclosure while maintaining a collectivistic orientation regarding self
      sacrifice in intimate relationships. Respondents' age, cultural group, and
      whether they were college students or professionals interacted with how strongly
      individuals rejected low self-disclosure and showed that age and status
      differences were more pronounced between rather than within the three cultural
      groups. It revealed that the initial finding, showing that Greeks and Americans
      differed, was based on the scores of students; professionals, with one exception,
      did not differ in their disagreement with low self-disclosure, regardless of
      their age and cultural group. The exception was the older Greek American
      professional subgroup, whose stronger disagreement with low self-disclosure may
      be an overreaction to the acculturation process. Age and status differences were
      not significant in the American group, while there was a pattern in Greece for
      professionals to reject low self-disclosure more strongly than did students.
      Women were more rejecting of both low self-disclosure and self-sacrifice in
      intimate relationships than were men. Older women most strongly disagreed with
      the self-sacrifice principle and older men adhered to it more strongly with
      increasing age.   Cette etude compare des Americains grecs a des Grecs et a des
      Americains blancs de troisieme generation relativement a leur adhesion a deux
      schemas cognitifs guidant les relations intimes. Les resultats indiquent que les
      Americains grecs se montrent plus rejetants d'une faible ouverture de soi dans
      les relations intimes comparativement aux Grecs, mais ils ne se differencient pas
      de ceux-ci quant a la force avec laquelle ils se disent prets a se sacrifier pour
      leur partenaire. En contrepartie, Americain grecs ne se differencient pas des
      Americains sur le plan du rejet de la faible ouverture de soi, tout en se
      montrant davantage en accord avec le sacrifice de soi dans les relations intimes
      que ne le font les Americains. Ces resultats sont interpretes comme des
      indicateurs que les Americains grecs auraient adopte la culture americaine
      d'orientation plus individualiste en ce qui a trait a l'ouverture de soi, tandis
      qu'ils semblent avoir maintenu une orientation collectiviste en regard du
      sacrifice de soi dans les relations intimes. L'age des repondants, leur groupe
      culturel et leur statut de collegien ou de professionnel montrent une interaction
      avec le degre de rejet de la faible ouverture de soi. Aussi, il appert que les
      differences d'age et de statut sont plus prononcees entre les trois groupes
      culturels qu'a l'interieur-meme de ces groupes. Les resultats indiquent que les
      donnees initiales, montrant que les Grecs et les Americains sont differents, sont
      basees sur les scores des etudiants; de facon generale, en regard des
      professionnels uniquement, aucune difference n'est soulevee pour le degre
      d'accord face a la faible ouverture de soi, peu importe leur age ou groupe
      culturel. Une exception apparait toutefois pour le sous-groupe d'Americains grecs
      professionnels et plus ages pour lequel le fort desaccord avec la faible
      ouverture de soi peut refleter une sur-reaction face au processus
      d'acculturation. Les differences d'age et de statut n'apparaissent pas
      significatives pour le groupe d'Americains, tandis qu'il semble y avoir un patron
      chez les professionels grecs a rejeter plus fortement la faible ouverture de soi
      comparativement aux etudiants grecs. Enfin, les femmes se montrent plus
      rejetantes a la fois en ce qui concerne la faible ouverture de soi et le
      sacrifice de soi dans les relations intimes comparativement aux hommes. Les
      femmes plus agees sont plus fortement en desaccord avec le principe de sacrifice
      de soi, tandis que les hommes plus ages y adherent davantage a mesure qu'ils
      vieillissent.   El estudio compara griegos estadounidenses con griegos y
      estadounidenses blancos de por lo menos tres generaciones respecto a que tanto se
      sentian representados por dos esquemas cognitivos de las relaciones intimas. Los
      griegos estadounidenses muestran mayor rechazo a revelar poco sobre si mismos en
      las relaciones intimas que los griegos, pero no difieren de estos en cuanto a que
      tanto se sacrificarian por la pareja. En contraste, los griegos estadounidenses
      no difirieron de los estadounidenses en su rechazo a revelar poco sobre si mismos
      a la pareja y apoyaron mas el auto sacrificio en las relaciones intimas que los
      estadounidenses. Estos hallazgos se interpretaron como indicativos de que los
      griegos estadounidenses se han aculturado a una orientacion mas individualista en
      terminos de que tanto revelan sobre si mismos, a la vez que han mantenido una
      orientacion colectivista respecto al auto sacrificio en las relaciones intimas.
      La edad, el grupo cultural, y la condicion de estudiante o profesional
      interactuaron con el rechazo a revelar poco sobre si mismo y mostro que la edad y
      la diferencia en la condicion de estudiante o profesional eran mas pronunciadas
      entre los tres grupos culturales que al interior de cada uno de estos. Revelo que
      el hallazgo inicial sobre la diferencia entre griegos y estadounidenses se basaba
      en las calificaciones de los estudiantes; los profesionales, con una excepcion,
      no diferian en cuanto a su desacuerdo con revelar poco sobre si mismos,
      independientemente de su edad y grupo cultural. La excepcion fue el subgrupo de
      profesionales griegos estadounidenses de mayor edad, cuyo mayor descuerdo con
      revelar poco sobre si mismo podria ser una reaccion exagerada al proceso de
      aculturacion. Las diferencias en la edad y en la condicion de estudiante o
      profesional no fueron significativas en el grupo de estadounidenses, en tanto que
      los profesionales griegos muestran una tendencia a rechazar con mayor fuerza el
      revelar poco sobre si mismos, en comparacion con los estudiantes. Las mujeres
      rechazan mas que los hombres tanto revelar poco sobre si mismas como el auto
      sacrificio en las relaciones intimas. Las mujeres de mayor edad discrepan con
      mayor fuerza con el principio de auto sacrificio, y a mayor edad en los hombres
      mayor adhesion a este.

PMID- 22587546
TI  - Human rights and ethnic attitudes in Spain: The role of cognitive, social status,
      and individual difference factors.

PMID- 22587547
TI  - Acculturation orientations towards Israeli Arabs and Jewish immigrants in Israel.

PMID- 22587548
TI  - Filial belief and parent-child conflict.

PMID- 22587549
TI  - Middle East and north Africa regional conference of psychology, dubai, United
      arab emirates.

PMID- 22587550
TI  - Congresses and scientific meetings.

PMID- 22587551
TI  - Nerve transfers for the restoration of hand function after spinal cord injury.
AB  - Spinal cord injury (SCI) remains a significant public health problem. Despite
      advances in understanding of the pathophysiological processes of acute and
      chronic SCI, corresponding advances in translational applications have lagged
      behind. Nerve transfers using an expendable nearby motor nerve to reinnervate a
      denervated nerve have resulted in more rapid and improved functional recovery
      than traditional nerve graft reconstructions following a peripheral nerve injury.
      The authors present a single case of restoration of some hand function following
      a complete cervical SCI utilizing nerve transfers.

PMID- 22587553
TI  - Public awareness and cervical cancer screening.

PMID- 22587554
TI  - The pathology clinic - pathologists should see patients.
AB  - This invited review describes why and how a pathologist should talk to patients
      in order to enhance the patient care pathway. The pathologist-patient interaction
      should become a natural extension to multidisciplinary team decision making, and
      also become the forum in which patients are helped to understand important
      aspects of their conditions and the pathological basis for their treatment plans.
      There is a vast amount of information available through the internet and to
      digest this can be a difficult process for a patient who is already having to
      cope with a medical condition. The pathologist is often best placed to sieve
      through this information and offer the patient the relevant detail necessary to
      understand the condition and the management pathway. Pathologists can provide up
      to-date, simple information about malignant and even certain significant benign
      conditions, and they can do this with the help of several pictorial tools. In
      this way, the pathologist becomes an even more active member of a clinical team
      and helps both clinicians and patients to deal with illnesses in a novel way
      hitherto not considered.

PMID- 22587555
TI  - How do the thiolate ligand and its relative position control the oxygen
      activation in the cysteine dioxygenase model?
AB  - In the iron(II)-thiolate models of cysteine dioxygenase, the thiolate ligand is a
      key factor in the oxygen activation. In this contribution, four model compounds
      have been theoretically investigated. This comparative study reveals that the
      thiolate ligand itself and its relative position are both important for the
      activation of O(2). Before the O(2) binding, the thiolate ligand must transfer
      charge to Fe(II), and the effective nuclear charges of Fe(II) is decreased, which
      results in a lower redox potential of compounds. In other words, the thiolate
      ligand provides a prerequisite for the O(2) activation. Furthermore, the relative
      position of the thiolate ligand is discovered to determine the reaction path of
      O(2) activation. The amount of charge transfer is crucial for these reactions;
      the more charge it transfers, the lower the related redox potentials. This work
      really helps think deeper into the O(2) activation process of mononuclear nonheme
      iron enzymes.

PMID- 22587556
TI  - Response of anaerobic granular sludge to a shock load of zinc oxide nanoparticles
      during biological wastewater treatment.
AB  - The increasing use of zinc oxide nanoparticles (ZnO NPs) in consumer and
      industrial products highlights a need to understand their potential environmental
      impacts. In this study, the response of anaerobic granular sludge (AGS) to a
      shock load of ZnO NPs during anaerobic biological wastewater treatment was
      reported. It was observed that the extracellular polymeric substances (EPS) of
      AGS and the methane production were not significantly influenced at ZnO NPs of 10
      and 50 mg per gram of total suspended solids (mg/g-TSS), but they were decreased
      when the dosage of ZnO NPs was greater than 100 mg/g-TSS. The visualization of
      EPS structure with multiple fluorescence labeling and confocal laser scanning
      microscope revealed that ZnO NPs mainly caused the decrease of proteins by 69.6%.
      The Fourier transform infrared spectroscopy analysis further indicated that the C
      O-C group of polysaccharides and carboxyl group of proteins in EPS were also
      changed in the presence of ZnO NPs. The decline of EPS induced by ZnO NPs
      resulted in their deteriorating protective role on the inner microorganisms of
      AGS, which was in correspondence with the observed lower general physiological
      activity of AGS and the death of microorganisms. Further investigation showed
      that the negative influence of ZnO NPs on methane production was due to their
      severe inhibition on the methanization step.

PMID- 22587558
TI  - Stereoselective synthesis by olefin metathesis and characterization of eta
      carotene (7,8,7',8'-tetrahydro-beta,beta-carotene).
AB  - The purported structure of the elusive eta-carotene (7,8,7',8'-tetrahydro
      beta,beta-carotene), a natural C(40) carotenoid first detected in the berries of
      Lonicera japonica and in citrus fruits sixty years ago, has been synthesized by
      olefin cross-metathesis/dimerization of a C(21) polyene derived from trans-7,8
      dihydroretinal, thus allowing the full characterization of this highly unstable
      natural product.

PMID- 22587557
TI  - Characterization and 454 pyrosequencing of major histocompatibility complex class
      I genes in the great tit reveal complexity in a passerine system.
AB  - BACKGROUND: The critical role of Major Histocompatibility Complex (Mhc) genes in
      disease resistance and their highly polymorphic nature make them exceptional
      candidates for studies investigating genetic effects on survival, mate choice and
      conservation. Species that harbor many Mhc loci and high allelic diversity are
      particularly intriguing as they are potentially under strong selection and
      studies of such species provide valuable information as to the mechanisms
      maintaining Mhc diversity. However comprehensive genotyping of complex multilocus
      systems has been a major challenge to date with the result that little is known
      about the consequences of this complexity in terms of fitness effects and disease
      resistance. RESULTS: In this study, we genotyped the Mhc class I exon 3 of the
      great tit (Parus major) from two nest-box breeding populations near Oxford, UK
      that have been monitored for decades. Characterization of Mhc class I exon 3 was
      adopted and bidirectional sequencing was carried using the 454 sequencing
      platform. Full analysis of sequences through a stepwise variant validation
      procedure allowed reliable typing of more than 800 great tits based on 214,357
      reads; from duplicates we estimated the repeatability of typing as 0.94. A total
      of 862 alleles were detected, and the presence of at least 16 functional loci was
      shown - the highest number characterized in a wild bird species. Finally, the
      functional alleles were grouped into 17 supertypes based on their antigen binding
      affinities. CONCLUSIONS: We found extreme complexity at the Mhc class I of the
      great tit both in terms of allelic diversity and gene number. The presence of
      many functional loci was shown, together with a pseudogene family and putatively
      non-functional alleles; there was clear evidence that functional alleles were
      under strong balancing selection. This study is the first step towards an in
      depth analysis of this gene complex in this species, which will help
      understanding how parasite-mediated and sexual selection shape and maintain host
      genetic variation in nature. We believe that study systems like ours can make
      important contributions to the field of evolutionary biology and emphasize the
      necessity of integrating long-term field-based studies with detailed genetic
      analysis to unravel complex evolutionary processes.

PMID- 22587559
TI  - HNF1B deletions in patients with young-onset diabetes but no known renal disease.
AB  - AIMS: Hepatocyte nuclear factor 1beta (HNF1B) mutations cause a syndrome of renal
      cysts and diabetes, with whole gene deletions accounting for approximately 50% of
      cases. The severity of the renal phenotype is variable, from enlarged cystic
      kidneys incompatible with life to normal renal development and function. We
      investigated the prevalence of HNF1B deletions in patients with diabetes but no
      known renal disease. METHODS: We tested 461 patients with familial diabetes
      diagnosed before 45 years, including 258 probands who met clinical criteria for
      maturity-onset diabetes of the young (two generations affected and at least one
      family member diagnosed under 25 years). A fluorescent polymerase chain reaction
      assay was used to analyse two intragenic polymorphic HNF1B markers and identify
      heterozygous patients who therefore did not have whole gene deletions. Those
      patients homozygous for both markers were then tested for an HNF1B deletion using
      multiplex ligation-dependent probe amplification. RESULTS: Heterozygous HNF1B
      intragenic polymorphisms were identified in 337/461 subjects. Multiplex ligation
      dependent probe amplification analysis showed an HNF1B gene deletion in three of
      the remaining 124 probands, all of whom met the criteria for maturity-onset
      diabetes of the young. Testing of their relatives identified three additional
      deletion carriers and ultrasound scanning showed renal developmental
      abnormalities in three of these six patients. CONCLUSIONS: We estimate that HNF1B
      mutations account for < 1% of cases of maturity-onset diabetes of the young.
      Although HNF1B mutations are a rare cause of diabetes in the absence of known
      renal disease, a genetic diagnosis of renal cysts and diabetes syndrome is
      important as it raises the possibility of subclinical renal disease and the 50%
      risk of renal cysts and diabetes syndrome in the patient's offspring.

PMID- 22587560
TI  - Preparation and enhancement of oral bioavailability of curcumin using
      microemulsions vehicle.
AB  - A new microemulsions system of curcumin (CUR-MEs) was successfully developed to
      improve the solubility and bioavailability of curcumin. Several formulations of
      the microemulsions system were prepared and evaluated using different ratios of
      oils, surfactants, and co-surfactants (S&CoS). The optimal formulation, which
      consists of Capryol 90 (oil), Cremophor RH40 (surfactant), and Transcutol P
      aqueous solution (co-surfactant), could enhance the solubility of curcumin up to
      32.5 mg/mL. The pharmacokinetic study of microemulsions was performed in rats
      compared to the corresponding suspension. The stability of microemulsions after
      dilution was excellence. Microemulsions have significantly increased the C(max)
      and area under the curve (AUC) in comparison to that in suspension (p < 0.05).
      The relative bioavailability of curcumin in microemulsions was 22.6-fold higher
      than that in suspension. The results indicated that the CUR-MEs could be used as
      an effective formulation for enhancing the oral bioavailability of curcumin.

PMID- 22587561
TI  - Transient receptor potential vanilloid-1 regulates osteoprotegerin/RANKL
      homeostasis in human periodontal ligament cells.
AB  - BACKGROUND AND OBJECTIVE: Increasing evidence has shown the presence of transient
      receptor potential vanilloid-1 (TRPV1) in a variety of nonneuronal tissues;
      however, the function of TRPV1 in these cells is not well understood. In this
      study, we aimed to investigate the expression and function of TRPV1 in human
      periodontal ligament (HPDL) cells. As HPDL cells are known to play an important
      role in the bone-remodeling process, we hypothesized that TRPV1 might be
      implicated in the regulation of osteoprotegerin (OPG) and RANKL expression.
      MATERIAL AND METHODS: TRPV1 expression was examined by western blot analysis. The
      function of TRPV1 was studied using capsaicin, a well-known TRPV1 agonist. RT-PCR
      was performed to study the expression of OPG and RANKL mRNAs. The expression of
      OPG and RANKL proteins was analyzed by ELISA and western blotting, respectively.
      The mechanisms of capsaicin-induced OPG expression in HPDL cells were studied
      using inhibitors. RESULTS: In this study we found that TRPV1 was present in HPDL
      cells. Treatment with capsaicin induced OPG expression in a dose-dependent manner
      but did not affect the expression of RANKL. The increase of the OPG/RANKL ratio
      was also found in human osteoblasts, but not in MC3T3-E1 cells, a mouse
      osteoblastic cell line, suggesting species specificity. Capsazepine, the
      competitive TRPV1 antagonist, significantly abolished the effect of capsaicin on
      OPG expression in HPDL cells. In addition, studies investigating the effects of a
      calcium chelator and a phospholipase C inhibitor indicated that calcium ions and
      phospholipase C were required for the induction. Interestingly, capsaicin was
      able to increase the OPG/RANKL ratio, even in the presence of prostaglandin E2, a
      potent inducer of RANKL. CONCLUSION: Our study demonstrates that activation of
      TRPV1 leads to an increase of the OPG/RANKL ratio in HPDL cells. These findings
      suggest the novel function of TRPV1 in periodontal tissues, at least, as the
      regulator of the OPG/RANKL axis.

PMID- 22587562
TI  - Experience with using second life for medical education in a family and community
      medicine education unit.
AB  - BACKGROUND: The application of new technologies to the education of health
      professionals is both a challenge and a necessity. Virtual worlds are
      increasingly being explored as a support for education. AIM: The aim of this work
      is to study the suitability of Second Life (SL) as an educational tool for
      primary healthcare professionals. METHODS:  DESIGN: Qualitative study of
      accredited clinical sessions in SL included in a continuing professional
      development (CPD) programme for primary healthcare professionals. LOCATION:
      Zaragoza I Zone Family and Community Medicine Education Unit (EU) and 9 health
      centres operated by the Aragonese Health Service, Aragon, Spain. METHOD: The EU
      held two training workshops in SL for 16 healthcare professionals from 9 health
      centres by means of two workshops, and requested them to facilitate clinical
      sessions in SL. Attendance was open to all personnel from the EU and the 9 health
      centres. After a trail period of clinical sessions held at 5 health centres
      between May and November 2010, the CPD-accredited clinical sessions were held at
      9 health centres between February and April 2011. PARTICIPANTS: 76 healthcare
      professionals attended the CPD-accredited clinical sessions in SL. MAIN
      MEASUREMENTS: Questionnaire on completion of the clinical sessions. RESULTS:
      Response rate: 42-100%. Questionnaire completed by each health centre on
      completion of the CPD-accredited clinical sessions: Access to SL: 2 centres were
      unable to gain access. Sound problems: 0% (0/9). Image problems: 0% (0/9).
      Voice/text chat: used in 100% (10/9); 0 incidents. Questionnaire completed by
      participants in the CPD-accredited clinical sessions: Preference for SL as a
      tool: 100% (76/76). Strengths of this method: 74% (56/76) considered it
      eliminated the need to travel; 68% (52/76) believed it made more effective use of
      educational resources; and 47% (36/76) considered it improved accessibility.
      Weaknesses: 91% (69/76) experienced technical problems, while; 9% (7/76) thought
      it was impersonal and with little interaction. 65.79% (50/76) believed it was
      better than other distance learning methods and 38.16% (29/76) believed it was
      better than face-to-face learning. CONCLUSIONS: SL is a tool that allows
      educational activities to be designed that involve a number of health centres in
      different geographical locations, consequently eliminating the need to travel and
      making more effective use of educational resources.

PMID- 22587563
TI  - Rapamycin slows aging in mice.
AB  - Rapamycin increases lifespan in mice, but whether this represents merely
      inhibition of lethal neoplastic diseases, or an overall slowing in multiple
      aspects of aging is currently unclear. We report here that many forms of age
      dependent change, including alterations in heart, liver, adrenal glands,
      endometrium, and tendon, as well as age-dependent decline in spontaneous
      activity, occur more slowly in rapamycin-treated mice, suggesting strongly that
      rapamycin retards multiple aspects of aging in mice, in addition to any
      beneficial effects it may have on neoplastic disease. We also note, however, that
      mice treated with rapamycin starting at 9 months of age have significantly higher
      incidence of testicular degeneration and cataracts; harmful effects of this kind
      will guide further studies on timing, dosage, and tissue-specific actions of
      rapamycin relevant to the development of clinically useful inhibitors of TOR
      action.

PMID- 22587564
TI  - Atrioventricular conduction after transcatheter aortic valve implantation and
      surgical aortic valve replacement.
AB  - INTRODUCTION: Atrioventricular conduction abnormalities (AVCA) may complicate
      transcatheter aortic valve implantation (TAVI) and surgical aortic valve
      replacement (SAVR). The aim of this study was to prospectively evaluate AVCA
      after TAVI and SAVR. METHODS AND RESULTS: Among 50 patients undergoing TAVI and
      25 patients undergoing SAVR a continuous 7-day Holter electrocardiogram (ECG) was
      recorded after the procedure. ECGs during TAVI and 12-lead ECGs before and 1 and
      7 days after TAVI and SAVR were analyzed. At baseline, TAVI patients were older
      (mean 82.1 vs 75.4, P < 0.001), had a longer PR interval (median 200 milliseconds
      vs 175 milliseconds, P = 0.004) and broader QRS width (median 100 milliseconds vs
      80 milliseconds, P = 0.007) than SAVR patients. New AVCA were observed among 29
      TAVI patients (58%), mostly new left bundle branch block (76%). Predilatation
      induced new AVCA in 14 TAVI patients (28%). New AVCA resolved within 24 hours in
      15 TAVI patients (30%), and persisted in 14 TAVI (28%) and 3 SAVR patients (12%,
      P = 0.12). Among patients with persistent QRS width <120 milliseconds during the
      first 24 hours after TAVI, QRS width remained stable during the remainder of the
      observation period. During Holter monitoring complete AV block was observed in 4
      TAVI patients (8%) and 3 SAVR patients (12%; P = 0.68). CONCLUSIONS: Almost half
      of AVCA during TAVI are induced by predilatation, but half of them resolve within
      24 hours. Persistent AVCA are more frequently observed after TAVI than SAVR. If
      QRS width is below 120 milliseconds the first day after TAVI, the risk of late
      AVCA seems low.

PMID- 22587565
TI  - Tree-average distances on certain phylogenetic networks have their weights
      uniquely determined.
AB  - A phylogenetic network N has vertices corresponding to species and arcs
      corresponding to direct genetic inheritance from the species at the tail to the
      species at the head. Measurements of DNA are often made on species in the leaf
      set, and one seeks to infer properties of the network, possibly including the
      graph itself. In the case of phylogenetic trees, distances between extant species
      are frequently used to infer the phylogenetic trees by methods such as neighbor
      joining. This paper proposes a tree-average distance for networks more general
      than trees. The notion requires a weight on each arc measuring the genetic change
      along the arc. For each displayed tree the distance between two leaves is the sum
      of the weights along the path joining them. At a hybrid vertex, each character is
      inherited from one of its parents. We will assume that for each hybrid there is a
      probability that the inheritance of a character is from a specified parent.
      Assume that the inheritance events at different hybrids are independent. Then for
      each displayed tree there will be a probability that the inheritance of a given
      character follows the tree; this probability may be interpreted as the
      probability of the tree. The tree-average distance between the leaves is defined
      to be the expected value of their distance in the displayed trees. For a class of
      rooted networks that includes rooted trees, it is shown that the weights and the
      probabilities at each hybrid vertex can be calculated given the network and the
      tree-average distances between the leaves. Hence these weights and probabilities
      are uniquely determined. The hypotheses on the networks include that hybrid
      vertices have indegree exactly 2 and that vertices that are not leaves have a
      tree-child. 

PMID- 22587566
TI  - Predicting chiral nanostructures, lattices and superlattices in complex
      multicomponent nanoparticle self-assembly.
AB  - "Bottom up" type nanoparticle (NP) self-assembly is expected to provide facile
      routes to nanostructured materials for various, for example, energy related,
      applications. Despite progress in simulations and theories, structure prediction
      of self-assembled materials beyond simple model systems remains challenging. Here
      we utilize a field theory approach for predicting nanostructure of complex and
      multicomponent hybrid systems with multiple types of short- and long-range
      interactions. We propose design criteria for controlling a range of NP based
      nanomaterial structures. In good agreement with recent experiments, the theory
      predicts that ABC triblock terpolymer directed assemblies with ligand-stabilized
      NPs can lead to chiral NP network structures. Furthermore, we predict that long
      range Coulomb interactions between NPs leading to simple NP lattices, when
      applied to NP/block copolymer (BCP) assemblies, induce NP superlattice formation
      within the phase separated BCP nanostructure, a strategy not yet realized
      experimentally. We expect such superlattices to be of increasing interest to
      communities involved in research on, for example, energy generation and storage,
      metamaterials, as well as microelectronics and information storage.

PMID- 22587567
TI  - Redox albuminomics: oxidized albumin in human diseases.
AB  - SIGNIFICANCE: Albumin is the major contributor to colloid oncotic pressure and
      also serves as an important carrier protein of many endogenous and exogenous
      molecules throughout the body. In blood and extravascular fluids, albumin is
      susceptible to different oxidative modifications, especially thiol oxidation and
      carbonylation. Because of its metal-binding properties and the redox properties
      of its Cys34 thiol, albumin displays an important antioxidant activity. As
      albumin is the predominant protein in most body fluids, its Cys34 represents the
      largest fraction of free thiols within body fluids. RECENT ADVANCES: Evidence
      that albumin oxidation takes place in vivo has been reported only recently.
      Different redox proteomic, mass spectrometric, and chromatographic techniques
      have shown albumin redox modifications in various human pathophysiological
      conditions. As a whole, most data here presented demonstrate that massive albumin
      oxidation occurs in vivo in different biological fluids and, to some extent, that
      this process is correlated to organ dysfunction. CRITICAL ISSUES: Recent reports
      suggest that the albumin redox state may serve as a global biomarker for the
      redox state in the body in various human diseases. However, further study is
      required to elucidate the exact relationship between albumin oxidation and
      pathology. In addition, it is unknown if some albumin oxidized forms may also
      have diagnostic uses. FUTURE DIRECTIONS: Application of specific redox proteomics
      techniques for the characterization of oxidized albumin forms in screening
      studies is required. A further challenge will be to analyze how these oxidative
      albumin modifications are related to real impact to the body.

PMID- 22587568
TI  - Interleukin-18 and interferon-gamma polymorphisms are implicated on proviral load
      and susceptibility to human T-lymphotropic virus type 1 infection.
AB  - Interleukin-18 (IL-18) and interferon-gamma (IFN-gamma) exert important functions
      in both innate and adaptive immune responses against intracellular pathogens and
      viruses. Previous studies suggested that host genetic factors, including
      cytokines gene polymorphisms, could be involved in the pathogenesis of human T
      cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP). Thus, we analyzed -137C/G and -607A/C of the IL-18
      promoter and +874T/A of the IFN-gamma in DNA samples from 98 HTLV-1-infected
      individuals exhibiting or not clinical symptoms and 150 healthy control
      individuals. The IL-18 promoter -607CC genotype was significantly lower in HTLV-1
      asymptomatic carriers (HAC) and HTLV-1-infected individuals (HAC + HAM/TSP) than
      healthy control group. In contrast, the -607AC genotype was significantly higher
      in HAC and HTLV-1-infected individuals group compared to the healthy control
      group. The -137G/-607A IL-18 haplotype was higher in infected group than healthy
      control group, and the -137C/-607C IL-18 haplotype was increased in the healthy
      control group compared to the others. Finally, the IFN-gamma polymorphism
      analysis showed that the HTLV-1-infected individuals with +874AT genotype
      presented higher proviral load than +874AA genotype. These data indicate that the
      IL-18-607AC genotype and -137G/-607A haplotype could be a risk factor for HTLV-1
      infection, whereas the protective effect could be conferred by -607CC genotype
      and -137C/-607C haplotype. Also, the IFN-gamma could be implicated on the
      proviral load levels.

PMID- 22587569
TI  - Overcoming the "coffee-stain" effect by compositional Marangoni-flow-assisted
      drop-drying.
AB  - Attempts at depositing uniform films of nanoparticles by drop-drying have been
      frustrated by the "coffee-stain" effect due to convective macroscopic flow into
      the contact line. Here, we show that uniform deposition of nanoparticles in
      aqueous suspensions can be attained easily by drying the droplet in an ethanol
      vapor atmosphere. This technique allows the particle-laden water droplets to
      spread on a variety of surfaces such as glass, silicon, mica, PDMS, and even
      Teflon. Visualization of droplet shape and internal flow shows initial droplet
      spreading and strong recirculating flow during spreading and shrinkage. The
      initial spreading is due to a diminishing contact angle from the absorption of
      ethanol from the vapor at the contact line. During the drying phase, the vapor is
      saturated in ethanol, leading to preferential evaporation of water at the contact
      line. This generates a surface tension gradient that drives a strong
      recirculating flow and homogenizes the nanoparticle concentration. We show that
      this method can be used for depositing catalyst nanoparticles for the growth of
      single-walled carbon nanotubes as well as to manufacture plasmonic films of well
      spaced, unaggregated gold nanoparticles.

PMID- 22587570
TI  - Differences in DNA curvature-related sequence periodicity between prokaryotic
      chromosomes and phages, and relationship to chromosomal prophage content.
AB  - BACKGROUND: Periodic spacing of A-tracts (short runs of A or T) with the DNA
      helical period of ~10-11 bp is characteristic of intrinsically bent DNA. In
      eukaryotes, the DNA bending is related to chromatin structure and nucleosome
      positioning. However, the physiological role of strong sequence periodicity
      detected in many prokaryotic genomes is not clear. RESULTS: We developed measures
      of intensity and persistency of DNA curvature-related sequence periodicity and
      applied them to prokaryotic chromosomes and phages. The results indicate that
      strong periodic signals present in chromosomes are generally absent in phage
      genomes. Moreover, chromosomes containing prophages are less likely to possess a
      persistent periodic signal than chromosomes with no prophages. CONCLUSIONS:
      Absence of DNA curvature-related sequence periodicity in phages could arise from
      constraints associated with DNA packaging in the viral capsid. Lack of prophages
      in chromosomes with persistent periodic signal suggests that the sequence
      periodicity and concomitant DNA curvature could play a role in protecting the
      chromosomes from integration of phage DNA.

PMID- 22587571
TI  - Kinetic metal release from competing processes in aquifers.
AB  - Understanding groundwater time scales wherein kinetic metal-desorption and
      mineral-dissolution are important mechanisms is essential for realistic modeling
      of metal release. In this study, release rate constants were compiled and the
      Damkohler number was applied to calculate residence times where kinetic
      formulations are relevant. Desorption rate constants were compiled for arsenic,
      barium, cadmium, copper, lead, mercury, nickel, and zinc, and span 6 orders of
      magnitude, while mineral-dissolution rate constants compiled for calcite,
      kaolinite, smectite, anorthite, albite, K-feldspar, muscovite, quartz, goethite,
      and galena ranged over 13 orders of magnitude. This Damkohler analysis
      demonstrated that metal-desorption kinetics are potentially influential at
      residence times up to about two years, depending on the metal and groundwater
      conditions. Kinetic mineral-dissolution should be considered for nearly all
      residence times relevant to groundwater modeling, provided the rate, solubility,
      and availability of the mineral generates a non-negligible concentration.
      Geochemical models of competitive desorption and dissolution for an illustrative
      metal demonstrate total metal concentrations may be sensitive to dissolution rate
      variations despite the predominance of release from desorption. Ultimately, this
      analysis provides constraints on relevant processes for incorporation into
      transport models.

PMID- 22587572
TI  - alpha-glucosidase inhibitors from Brickellia cavanillesii.
AB  - An aqueous extract from the aerial parts of Brickellia cavanillesii attenuated
      postprandial hyperglycemia in diabetic mice during oral glucose and sucrose
      tolerance tests. Experimental type-II DM was achieved by treating mice with
      streptozotocin (100 mg/kg) and beta-nicotinamide adenine dinucleotide (40 mg/kg).
      These pharmacological results demonstrated that B. cavanillesii is effective for
      controlling fasting and postprandial blood glucose levels in animal models. The
      same aqueous extract also showed potent inhibitory activity (IC(50) = 0.169 vs
      1.12 mg/mL for acarbose) against yeast alpha-glucosidase. Bioassay-guided
      fractionation of the active extract using the alpha-glucosidase inhibitory assay
      led to the isolation of several compounds including two chromenes [6-acetyl-5
      hydroxy-2,2-dimethyl-2H-chromene (1) and 6-hydroxyacetyl-5-hydroxy-2,2-dimethyl
      2H-chromene (2)], two sesquiterpene lactones [caleins B (3) and C (4)], several
      flavonoids [acacetin (5), genkwanin (6), isorhamnetin (7), kaempferol (8), and
      quercetin (9)], and 3,5-di-O-caffeoylquinic acid (10). Chromene 2 is a new
      chemical entity. Compounds 2, 4, 7, and 9 inhibited the activity of yeast alpha
      glucosidase with IC(50) 0.42, 0.28, 0.16, and 0.53 mM, respectively, vs 1.7 mM
      for acarbose. Kinetic analysis revealed that compounds 4 and 7 behaved as mixed
      type inhibitors with K(i) values of 1.91 and 0.41 mM, respectively, while 2 was
      noncompetititive, with a K(i) of 0.13 mM. Docking analysis predicted that these
      compounds, except 2, bind to the enzyme at the catalytic site.

PMID- 22587573
TI  - Effect of ketorolac 0.5% drops on patients' pain perception during intravitreal
      injection procedure.
AB  - PURPOSE: To evaluate the analgesic effect of ketorolac 0.5% drops during the
      intravitreal injection procedure. METHODS: Thirty patients (n=30) received
      topical ketorolac 0.5% or vehicle on subsequent intravitreal drug
      administrations. The procedure followed for the intravitreal injections was the
      same for all subsequent administrations with the use of tetracaine 0.5% drops as
      anesthetic. Ketorolac or vehicle was instilled before the injection, and pain
      perception was recorded on a 0 to 100 Visual Analog Scale (VAS) immediately after
      the intravitreal administration. RESULTS: Mean VAS pain score was 8.16+/-1.3 when
      patients received ketorolac and 12.33+/-1.41 when they received placebo, a
      difference that was statistically significant (P=0.0003) (paired t-test).
      CONCLUSIONS: Topical ketorolac 0.5% reduces patients' pain perception during
      intravitreal drug administration.

PMID- 22587574
TI  - Benchmark studies on the building blocks of DNA. 1. Superiority of coupled
      cluster methods in describing the excited states of nucleobases in the Franck
      Condon region.
AB  - Equation of motion excitation energy coupled-cluster (EOMEE-CC) methods including
      perturbative triple excitations have been used to set benchmark results for the
      excitation energy and oscillator strength of the building units of DNA, i.e.,
      cytosine, guanine, adenine and thymine. In all cases the lowest twelve
      transitions have been considered including valence and Rydberg ones. Triple-zeta
      basis sets with diffuse functions have been used and the results are compared to
      CC2, CASPT2, TDDFT, and DFT/MRCI results from the literature. The results clearly
      show that it is only the EOMEE-CCSD(T) that is capable of providing accuracy of
      about 0.1 eV. EOMEE-CCSD systematically overshoots the energy of all types of
      transitions by 0.1-0.3 eV, whereas CC2 is surprisingly accurate for pipi*
      transitions but fails (often badly) for npi* and Rydberg transitions. DFT and
      CASPT2 seem to give reliable results for the lowest transition, but the error
      increases fast with the excitation level. The differences in the excitation
      energies often change the energy ordering of the states, which should even
      influence the conclusions of excited state dynamics obtained with these
      approximate methods. The results call for further benchmark calculations on
      larger building blocks of DNA (nucleosides, basis pairs) at the CCSD(T) level.

PMID- 22587575
TI  - Development of multiresidue analysis for twenty phthalate esters in edible
      vegetable oils by microwave-assisted extraction-gel permeation chromatography
      solid phase extraction-gas chromatography-tandem mass spectrometry.
AB  - A novel multiresidue analysis method is developed for the determination of twenty
      phthalate esters at the MUg/kg level in edible vegetable oils by microwave
      assisted extraction-gel permeation chromatography-solid phase extraction-high
      resolution gas chromatography-tandem mass spectrometry (MAE-GPC-SPE-HRGC-MS/MS).
      The samples were extracted with methanol under microwave incubation. Cleanup was
      carried out with GPC followed by a further C18 SPE column and then separated by
      the HP-5MS capillary column under a temperature program. The eluents were
      qualitatively and quantitatively determined by tandem mass analyzer with selected
      reaction monitoring (SRM) type and positive ion mode. The calibration curves
      showed good linearity in the range 5 MUg/kg to 2.50 mg/kg with correlation
      coefficients larger than 0.999. Low detection limits (LODs) of 0.218-1.367 MUg/kg
      and quantification limits (LOQ) of 0.72-4.51 MUg/kg were achieved. The mean
      recoveries were in the range from 93.04% to 104.6% at 5, 15, and 40 MUg/kg spiked
      levels, and the relative standard deviations (RSDs) were in the range of 1.01%
      and 5.26% (n = 7). This method could potentially overcome the interference from
      large amounts of lipids and pigment. The real sample test showed this method can
      be used for sensitive and accurate determination and confirmation of phthalate
      ester residues in high-fat and complex samples.

PMID- 22587578
TI  - Upcoming New Feature in the Journal of Biomolecular Structure & Dynamics.

PMID- 22587580
TI  - The use of artificial neural networks in electrostatic force microscopy.
AB  - The use of electrostatic force microscopy (EFM) to characterize and manipulate
      surfaces at the nanoscale usually faces the problem of dealing with systems where
      several parameters are not known. Artificial neural networks (ANNs) have
      demonstrated to be a very useful tool to tackle this type of problems. Here, we
      show that the use of ANNs allows us to quantitatively estimate magnitudes such as
      the dielectric constant of thin films. To improve thin film dielectric constant
      estimations in EFM, we first increase the accuracy of numerical simulations by
      replacing the standard minimization technique by a method based on ANN learning
      algorithms. Second, we use the improved numerical results to build a complete
      training set for a new ANN. The results obtained by the ANN suggest that accurate
      values for the thin film dielectric constant can only be estimated if the thin
      film thickness and sample dielectric constant are known.PACS: 07.79.Lh; 07.05.Mh;
      61.46.Fg.

PMID- 22587581
TI  - Etiology, diagnosis, and management of uterine leiomyomas.
AB  - Uterine leiomyomas are the most common benign gynecologic tumors. While the true
      etiology of leiomyomas remains unknown, their origin is thought to be
      multifactorial including genetic, hormonal, and tissue growth factor variations.
      Leiomyomas are predominantly found in women of reproductive age and are the
      leading indication for hysterectomy worldwide. Menstrual irregularities, pain,
      and fertility difficulties may arise from leiomyoma presence, although many women
      remain asymptomatic. Diagnosis can be made via ultrasound or magnetic resonance
      imaging, when precise mapping of the tissue is needed. Many treatment options are
      available ranging from surgical to medical and should be chosen depending on
      symptom severity, number and size of leiomyomas, patient age, fertility desires,
      and patient preferences. The objective of this article is to present a practical
      clinical perspective on uterine leiomyomas and an overview of contemporary
      treatment options.

PMID- 22587582
TI  - Secondary processing of red cells - adding insult to injury.

PMID- 22587584
TI  - Compositional dependence of the open-circuit voltage in ternary blend bulk
      heterojunction solar cells based on two donor polymers.
AB  - Ternary blend bulk heterojunction (BHJ) solar cells containing as donor polymers
      two P3HT analogues, high-band-gap poly(3-hexylthiophene-co-3-(2
      ethylhexyl)thiophene) (P3HT(75)-co-EHT(25)) and low-band-gap poly(3
      hexylthiophene-thiophene-diketopyrrolopyrrole) (P3HTT-DPP-10%), with phenyl-C(61)
      butyric acid methyl ester (PC(61)BM) as an acceptor were studied. When the ratio
      of the three components was varied, the open-circuit voltage (V(oc)) increased as
      the amount of P3HT(75)-co-EHT(25) increased. The dependence of V(oc) on the
      polymer composition for the ternary blend regime was linear when the overall
      polymer:fullerene ratio was optimized for each polymer:polymer ratio. Also, the
      short-circuit current densities (J(sc)) for the ternary blends were bettter than
      those of the binary blends because of complementary polymer absorption, as
      verified using external quantum efficiency measurements. High fill factors (FF)
      (>0.59) were achieved in all cases and are attributed to high charge-carrier
      mobilities in the ternary blends. As a result of the intermediate V(oc),
      increased J(sc) and high FF, the ternary blend BHJ solar cells showed power
      conversion efficiencies of up to 5.51%, exceeding those of the corresponding
      binary blends (3.16 and 5.07%). Importantly, this work shows that upon
      optimization of the overall polymer:fullerene ratio at each polymer:polymer
      ratio, high FF, regular variations in V(oc), and enhanced J(sc) are possible
      throughout the ternary blend composition regime. This adds to the growing
      evidence that the use of ternary blends is a general and effective strategy for
      producing efficient organic photovoltaics manufactured in a single active-layer
      processing step.

PMID- 22587585
TI  - Low rate of atrial fibrillation recurrence verified by implantable loop recorder
      monitoring following a convergent epicardial and endocardial ablation of atrial
      fibrillation.
AB  - OBJECTIVE: Evaluate long-term outcomes in patients undergoing the Convergent
      procedure (CP) for the treatment of atrial fibrillation (AF). BACKGROUND: The CP
      provides a multidisciplinary approach, combining endoscopic creation of
      epicardial linear lesions followed by endocardial mapping and ablation and
      targets persistent and longstanding persistent AF patients who are at increased
      risk of heart failure, stroke, and mortality. METHODS: Outcomes from a
      prospective nonrandomized study were recorded for consecutive patients by
      interrogation of implanted Reveal monitors. Rhythm status and AF burden were
      quantified 6-24 months postprocedure, and compared relative to AF type, gender,
      age, body mass index, left atrial size, left ventricular ejection fraction, and
      congestive heart failure, hypertension, age >75 years, age between 65 and 74
      years, stroke/TIA/TE, vascular disease (previous MI, peripheral arterial disease
      or aortic plaque), diabetes mellitus, female (CHA(2) DS(2) VASc). RESULTS: A
      total of 50 patients were enrolled with 94% having persistent or longstanding
      persistent AF. There were 2 atrioesophageal fistulas reported. In one patient,
      the fistula resulted in death at 33 days postprocedure; in the second, the
      fistula was surgically repaired but patient died 8 months postprocedure from a
      CVI. After CP, 95% of patients were in sinus rhythm at 6-month follow-up; 88% at
      12 months; and 87% at 24 months. The median AF burden recorded with Reveal XT
      monitors was 0.0%, 0.1%, and 0.1% at 6, 12, and 24 months with 81%, 81%, and 87%
      of patients reporting a burden less than 3%, respectively. CONCLUSION: Using 24 *
      7 continuous loop recording, the CP demonstrated success in treating persistent
      and longstanding persistent AF patients. Endocardial mapping and catheter
      ablation with diagnostic confirmation of procedural success complemented the
      endoscopic creation of epicardial linear lesions in restoring sinus rhythm.

PMID- 22587586
TI  - Study protocol for a pilot study to explore the determinants of knowledge use in
      a medical education context.
AB  - RATIONALE, AIMS AND OBJECTIVES: While the science of knowledge translation (KT)
      has been growing steadily for the past decade in relation to understanding
      processes and actions which are embedded within clinical practice settings,
      little is known about how empirical knowledge is used within the medical
      education system. Despite an increase of research in this domain, we know very
      little about the contribution of this evidence in the development of medical
      students into effective physicians. This pilot study aims to: provide a synthesis
      of the evidence for educational strategies within medical education; explore the
      perceptions and experiences of faculty in undergraduate (UG) medical education in
      relation to their use of evidence in their educational practices; and illuminate
      how medical education evidence is formally integrated into a UG medical
      curriculum. METHOD: The study will involve three phases. First, a scoping review
      of the medical education research literature will be undertaken to generate
      insight into the evidence available for curriculum development, teaching and
      assessment activities within this domain. Second, a content analysis of
      undergraduate courses at the University of Toronto will be undertaken to generate
      an additional insight into the extent that medical education research has been
      formally integrated into the UG curriculum for medical students at the
      University. Finally, a purposeful sample of 30-40 medical education leaders from
      a single large university, selected as it aims to deliver a rigorous research
      oriented medical curriculum, will be interviewed to understand how they use the
      available evidence in their education practices. DISCUSSION: This study will lay
      the grounds to generate initial data into the determinants of knowledge use in a
      medical education context. In doing so, the findings will also inform the
      development of a larger, pan-Canadian study at medical schools that will generate
      a comprehensive account of the processes and challenges related to KT within an
      educational context. This larger study will also begin to explore the relevance
      of the Knowledge-to-Action model to a medical education context.

PMID- 22587587
TI  - Accessing maternal and child health services in Melbourne, Australia: reflections
      from refugee families and service providers.
AB  - BACKGROUND: Often new arrivals from refugee backgrounds have experienced poor
      health and limited access to healthcare services. The maternal and child health
      (MCH) service in Victoria, Australia, is a joint local and state government
      operated, cost-free service available to all mothers of children aged 0-6 years.
      Although well-child healthcare visits are useful in identifying health issues
      early, there has been limited investigation in the use of these services for
      families from refugee backgrounds. This study aims to explore experiences of
      using MCH services, from the perspective of families from refugee backgrounds and
      service providers. METHODS: We used a qualitative study design informed by the
      socioecological model of health and a cultural competence approach. Two
      geographical areas of Melbourne were selected to invite participants. Seven focus
      groups were conducted with 87 mothers from Karen, Iraqi, Assyrian Chaldean,
      Lebanese, South Sudanese and Bhutanese backgrounds, who had lived an average of
      4.7 years in Australia (range one month-18 years). Participants had a total of
      249 children, of these 150 were born in Australia. Four focus groups and five
      interviews were conducted with MCH nurses, other healthcare providers and
      bicultural workers. RESULTS: Four themes were identified: facilitating access to
      MCH services; promoting continued engagement with the MCH service; language
      challenges; and what is working well and could be done better. Several processes
      were identified that facilitated initial access to the MCH service but there were
      implications for continued use of the service. The MCH service was not formally
      notified of new parents arriving with young children. Pre-arranged group
      appointments by MCH nurses for parents who attended playgroups worked well to
      increase ongoing service engagement. Barriers for parents in using MCH services
      included access to transportation, lack of confidence in speaking English and
      making phone bookings. Service users and providers reported that continuity of
      nurse and interpreter is preferred for increasing client-provider trust and
      ongoing engagement. CONCLUSIONS: Although participants who had children born in
      Melbourne had good initial access to, and experience of, using MCH services,
      significant barriers remain. A systems-oriented, culturally competent approach to
      service provision would improve the service utilisation experience for parents
      and providers, including formalising links and notifications between settlement
      services and MCH services.

PMID- 22587589
TI  - Catalytic asymmetric sulfenylation of unprotected 3-substituted oxindoles.
AB  - Catalytic asymmetric sulfenylation of unprotected 3-substituted oxindoles has
      been developed via cooperative catalysis of a chiral N,N'-dioxide-Sc(OTf)(3)
      complex and a Bronsted base. Utilizing readily available N
      (phenylthio)phthalimide as the sulfur source, a wide range of optically active 3
      phenylthiooxindoles were obtained in excellent yields with excellent
      enantioselectivities under mild reaction conditions.

PMID- 22587588
TI  - Thoracic hyperextension injury with complete "bony disruption" of the thoracic
      cage: Case report of a potentially life-threatening injury.
AB  - BACKGROUND: Severe chest wall injuries are potentially life-threatening injuries
      which require a standardized multidisciplinary management strategy for prevention
      of posttraumatic complications and adverse outcome. CASE PRESENTATION: We report
      the successful management of a 55-year old man who sustained a complete "bony
      disruption" of the thoracic cage secondary to an "all-terrain vehicle" roll-over
      accident. The injury pattern consisted of a bilateral "flail chest" with serial
      segmental rib fractures, bilateral hemo-pneumothoraces and pulmonary contusions,
      bilateral midshaft clavicle fractures, a displaced transverse sternum fracture
      with significant diastasis, and an unstable T9 hyperextension injury. After
      initial life-saving procedures, the chest wall injuries were sequentially
      stabilized by surgical fixation of bilateral clavicle fractures, locked plating
      of the displaced sternal fracture, and a two-level anterior spine fixation of the
      T9 hyperextension injury. The patient had an excellent radiological and
      physiological outcome at 6 months post injury. CONCLUSION: Severe chest wall
      trauma with a complete "bony disruption" of the thoracic cage represents a rare,
      but detrimental injury pattern. Multidisciplinary management with a staged timing
      for addressing each of the critical injuries, represents the ideal approach for
      an excellent long-term outcome.

PMID- 22587590
TI  - Disentangling respiratory acclimation and adaptation to growth temperature by
      Eucalyptus.
AB  - * Respiratory acclimation to growth temperature differs between species, but
      underlying mechanisms are poorly understood. In the present study, we tested the
      hypothesis that respiratory acclimation of CO(2) release is a consequence of
      growth regulation such that growth rates of young foliage of Eucalyptus spp. are
      similar at contrasting growth temperatures. Further, we tested whether such a
      response is affected by adaptation of Eucalyptus to different thermal
      environments via growth at different altitudes in the Australian Alps. * We
      employed calorimetric methods to relate rates of CO(2) release (mainly from
      substrate oxidation) and rates of O(2) reduction to conservation of energy.
      Temperature responses of these processes provided insight into mechanisms that
      control energy conservation and expenditure, and helped define 'instantaneous
      enthalpic growth capacity' (CapG). * CapG increased with altitude, but was
      counteracted by other factors in species adapted to highland habitats. The
      acclimation response was partly driven by changes in respiratory capacity
      (CapR(CO2)), and partly by more pronounced dynamic responses of CO(2) release
      (delta(R(CO2))) to measurement temperature. We observed enhanced temperature
      sensitivity of O(2) reduction (E(o)(R(O2))) at higher altitudes. * Adaptation to
      growth temperature included differences in respiration and growth capacities, but
      there was little evidence that Eucalyptus species vary in metabolic flexibility.

PMID- 22587591
TI  - Evaluation of methods for cultivating limbal mesenchymal stromal cells.
AB  - BACKGROUND AIMS: Mesenchymal stromal cells (MSC) with similar properties to bone
      marrow-derived mesenchymal stromal cells (BM-MSC) have recently been grown from
      the limbus of the human cornea. We have evaluated methods for culturing human
      limbal MSC (L-MSC). METHODS: Four basic strategies were compared: serum
      supplemented medium (10% fetal bovine serum; FBS), standard serum-free medium
      supplemented with B-27, epidermal growth factor and fibroblast growth factor 2,
      or one of two commercial serum-free media, defined keratinocyte serum-free medium
      (Invitrogen) and MesenCult-XF(r) (Stem Cell Technologies). The resulting cultures
      were examined using photography, flow cytometry (for CD34, CD45, CD73, CD90,
      CD105, CD141 and CD271), immunocytochemistry (alpha-smooth muscle actin; alpha
      sma), differentiation assays (osteogenesis, adipogenesis and chrondrogenesis) and
      co-culture experiments with human limbal epithelial (HLE) cells. RESULTS: While
      all techniques supported the establishment of cultures to varying degrees,
      sustained growth and serial propagation were only achieved in 10% FBS medium or
      MesenCult-XF medium. Cultures established in 10% FBS medium were 70-80% CD34(-)
      CD45(-) CD90 (+) CD73 (+) CD105 (+) , approximately 25% alpha-sma (+) and
      displayed multipotency. Cultures established in MesenCult-XF were > 95% CD34(-)
      CD45(-) CD90 (+) CD73 (+) CD105 (+) , 40% CD141 (+) , rarely expressed alpha-sma,
      and displayed multipotency. L-MSC supported growth of HLE cells, with the largest
      epithelial islands being observed in the presence of MesenCult-XF-grown L-MSC.
      All HLE cultures supported by L-MSC widely expressed the progenitor cell marker
      ?Np63, along with the corneal differentiation marker cytokeratin 3. CONCLUSIONS:
      MesenCult-XF is a superior culture system for L-MSC, but further studies are
      required to explore the significance of CD141 expression in these cells.

PMID- 22587592
TI  - Effect of culture media on expansion properties of human umbilical cord matrix
      derived mesenchymal cells.
AB  - BACKGROUND AIMS: Mesenchymal stromal cells (MSC) have been isolated from a number
      of different tissues, including umbilical cord. Because of the lack of a uniform
      approach to human umbilical cord matrix-derived mesenchymal (hUCM) cell
      expansion, we attempted to identify the optimum conditions for the production of
      a high quantity of hUCM cells by comparing two media. METHODS: We compared the
      ability of Dulbecco's Modified Eagle's Medium/F12 (DMEM/F12) and Alpha Minimum
      Essential Medium (alpha-MEM) with Glutamax (GL) (alpha-MEM/GL) to expand hUCM
      cells. For this purpose, hUCM cells were cultured in plates containing different
      culture media supplemented with 10% fetal bovine serum (FBS). Culture dishes were
      left undisturbed for 10-14 days to allow propagation of the newly formed hUCM
      cells. The expansion properties, CD marker expression, differentiation potential,
      population doubling time (PDT) and cell activity were compared between the two
      groups. RESULTS: The hUCM cells harvested from each group were positive for MSC
      markers, including CD44, CD90 and CD105, while they were negative for the
      hematopoietic cell surface marker CD34. Differentiation into adipogenic and
      osteogenic lineages was confirmed for both treatments. Cell activity was higher
      in the alpha-MEM/GL group than the DMEM/F12 group. PDT was calculated to be 60 h
      for the DMEM/F12 group, while for the alpha-MEM/GL group it was 47 h.
      CONCLUSIONS: Our data reveal that alpha-MEM/GL with 10% FBS supports hUCM cell
      growth more strongly than DMEM/F12 with 10% FBS.

PMID- 22587593
TI  - Decreased GAD(65)-specific Th1/Tc1 phenotype in children with Type 1 diabetes
      treated with GAD-alum.
AB  - AIM: The balance between T helper cell subsets is an important regulator of the
      immune system and is often examined after immune therapies. We aimed to study the
      immunomodulatory effect of glutamic acid decarboxylase (GAD) 65 formulated with
      aluminium hydroxide (GAD-alum) in children with Type 1 diabetes, focusing on
      chemokines and their receptors. METHODS: Blood samples were collected from 70
      children with Type 1 diabetes included in a phase II clinical trial with GAD
      alum. Expression of CC chemokine receptor 5 (CCR5) and CCR4 was analysed on CD4+
      and CD8+ lymphocytes after in vitro stimulation with GAD(65) using flow
      cytometry, and secretion of the chemokines CCL2, CCL3 and CCL4 was detected in
      peripheral blood mononuclear cell supernatants with Luminex. RESULTS: Expression
      of Th1-associated CCR5 was down-regulated following antigen challenge, together
      with an increased CCR4/CCR5 ratio and CCL2 secretion in GAD-alum-treated
      patients, but not in the placebo group. CONCLUSION: Our results suggest that GAD
      alum treatment has induced a favourable immune modulation associated with
      decreased Th1/Tc1 phenotypes upon antigen re-challenge, which may be of
      importance for regulating GAD(65) immunity.

PMID- 22587594
TI  - Effect of bioaugmentation and biostimulation on sulfate-reducing column startup
      captured by functional gene profiling.
AB  - Sulfate-reducing permeable reactive zones (SR-PRZs) depend upon a complex
      microbial community to utilize a lignocellulosic substrate and produce sulfides,
      which remediate mine drainage by binding heavy metals. To gain insight into the
      impact of the microbial community composition on the startup time and pseudo
      steady-state performance, functional genes corresponding to cellulose-degrading
      (CD), fermentative, sulfate-reducing, and methanogenic microorganisms were
      characterized in columns simulating SR-PRZs using quantitative polymerase chain
      reaction (qPCR) and denaturing gradient gel electrophoresis (DGGE). Duplicate
      columns were bioaugmented with sulfate-reducing or CD bacteria or biostimulated
      with ethanol or carboxymethyl cellulose and compared with baseline dairy manure
      inoculum and uninoculated controls. Sulfate removal began after ~ 15 days for all
      columns and pseudo-steady state was achieved by Day 30. Despite similar
      performance, DGGE profiles of 16S rRNA gene and functional genes at pseudo-steady
      state were distinct among the column treatments, suggesting the potential to
      control ultimate microbial community composition via bioaugmentation and
      biostimulation. qPCR revealed enrichment of functional genes in all columns
      between the initial and pseudo-steady-state time points. This is the first
      functional gene-based study of CD, fermentative and sulfate-reducing bacteria and
      methanogenic archaea in a lignocellulose-based environment and provides new
      qualitative and quantitative insight into startup of a complex microbial system.

PMID- 22587595
TI  - Spectrophotometric titration of bimetallic metal cation binding in
      polyamido(amine) dendrimer templates.
AB  - Spectrophotometric titration and a binding isotherm were used to accurately
      assess the loading capacity of generation four polyamido(amine) (PAMAM) dendrimer
      templates with terminal alcohol groups (G4-OH). Preparation of bimetallic G4-OH
      dendrimer-encapsulated metal nanoclusters (DENs) necessitates knowledge of the
      precise metal-ion binding capacity. The binding of metal ions such as Pt(2+) and
      Pd(2+) has proven difficult to assess via UV-vis spectroscopy because the
      absorbance shifts associated with metal-ion binding within the dendrimer template
      are masked by the absorbance of the PAMAM dendrimer itself. In contrast, the
      binding of Cu(2+) to G4-OH PAMAM dendrimer results in a strong, distinct
      absorption band at 300 nm, making UV-vis spectrophotometric titration with copper
      straightforward. Here we use copper binding as a means to assess the number of
      binding sites remaining within the PAMAM G4-OH dendrimer after the complexation
      of a specified molar excess of Pd(2+) or Pt(2+). In addition, we use a binding
      isotherm to mathematically estimate the loading capacity of the dendrimer in each
      case. The loading capacities for M(2+) in the G4-OH dendrimer were found to be
      ~16 for copper alone, ~21 for copper combined with palladium, and ~25 for copper
      combined with platinum.

PMID- 22587597
TI  - "Tram track effect" after treatment of acne scars using a microneedling device.

PMID- 22587596
TI  - In-silico predictive mutagenicity model generation using supervised learning
      approaches.
AB  - BACKGROUND: Experimental screening of chemical compounds for biological activity
      is a time consuming and expensive practice. In silico predictive models permit
      inexpensive, rapid "virtual screening" to prioritize selection of compounds for
      experimental testing. Both experimental and in silico screening can be used to
      test compounds for desirable or undesirable properties. Prior work on prediction
      of mutagenicity has primarily involved identification of toxicophores rather than
      whole-molecule predictive models. In this work, we examined a range of in silico
      predictive classification models for prediction of mutagenic properties of
      compounds, including methods such as J48 and SMO which have not previously been
      widely applied in cheminformatics. RESULTS: The Bursi mutagenicity data set
      containing 4337 compounds (Set 1) and a Benchmark data set of 6512 compounds (Set
      2) were taken as input data set in this work. A third data set (Set 3) was
      prepared by joining up the previous two sets. Classification algorithms including
      Naive Bayes, Random Forest, J48 and SMO with 10 fold cross-validation and default
      parameters were used for model generation on these data sets. Models built using
      the combined performed better than those developed from the Benchmark data set.
      Significantly, Random Forest outperformed other classifiers for all the data
      sets, especially for Set 3 with 89.27% accuracy, 89% precision and ROC of 95.3%.
      To validate the developed models two external data sets, AID1189 and AID1194,
      with mutagenicity data were tested showing 62% accuracy with 67% precision and
      65% ROC area and 91% accuracy, 91% precision with 96.3% ROC area respectively. A
      Random Forest model was used on approved drugs from DrugBank and metabolites from
      the Zinc Database with True Positives rate almost 85% showing the robustness of
      the model. CONCLUSION: We have created a new mutagenicity benchmark data set with
      around 8,000 compounds. Our work shows that highly accurate predictive
      mutagenicity models can be built using machine learning methods based on chemical
      descriptors and trained using this set, and these models provide a complement to
      toxicophores based methods. Further, our work supports other recent literature in
      showing that Random Forest models generally outperform other comparable machine
      learning methods for this kind of application.

PMID- 22587598
TI  - Fibroblast growth factor receptor 4 polymorphisms are associated with coronary
      artery disease.
AB  - Fibroblast growth factor receptor 4 (FGFR4) plays crucial roles in vascular
      smooth muscle cell proliferation and atherosclerosis and, therefore, may
      potentially affect the development of coronary artery disease (CAD). The aim of
      this study was to investigate the association between FGFR4 polymorphisms and the
      susceptibility to CAD in the Chinese population. Two polymorphisms,
      rs192201146G/A (Asp756Asn) and rs188755817C/G (Ser778Arg), were detected by
      polymerase chain reaction-restriction fragment length polymorphism and direct
      sequencing in 722 CAD cases and 802 age-matched controls. Data were analyzed
      using the chi-square test. Results showed that frequencies of rs192201146GA
      genotype and rs188755817CG genotype were significantly higher in CAD patients
      than in controls (odds ratio [OR]=1.92, 95% confidence interval [CI] 1.11-3.28,
      p=0.016, and OR=1.87, 95% CI 1.06-3.30, p=0.027). Similarly, numbers of the
      rs192201146A allele and the rs188755817G allele were significantly increased in
      CAD cases (OR=1.89, 95% CI 1.11-3.22, p=0.017, and OR=1.85, 95% CI 1.06-3.24,
      p=0.029). Haplotype analysis revealed that GG and AC (rs192201146 rs188755817)
      haplotypes had higher frequencies in CAD patients (OR=2.75, p=0.002 and OR=2.69,
      p=0.001). Our data suggested that the FGFR4 rs192201146 (Asp756Asn) and
      rs188755817 (Ser778Arg) polymorphisms could act as risk factors for CAD in the
      Chinese population.

PMID- 22587599
TI  - Leiden V factor and spastic cerebral palsy in Mexican children.
AB  - AIM: Cerebral palsy (CP) is a persistent motor disorder that appears before the
      patient is 3 years old due to a nonprogressive interference in the brain's
      development which takes place before the central nervous system growth is
      complete. Causes of this have been studied, and one that has been proposed for
      spastic hemiparesis CP is the Leiden mutation of V factor coagulation. We want to
      know whether this mutation can cause CP in our population. MATERIALS AND METHODS:
      We carried out a study of cases and controls with 94 patients with spastic
      hemiparesis CP and 120 controls as well as their mothers with their controls.
      RESULTS: None of the patients, their mothers, or controls had the Leiden
      mutation; however, other risk factors were significant: hypoxia odds ratio (OR)
      7.189 (2.546, 20.302) p=0.0001, smoking OR 16.621 (2.945, 93.818) p=0.001,
      maternal infections (urinary or vaginal) OR 7.040 (2.952, 16.789) p=0.0001, weeks
      of gestation OR 0.866 (0.7750, 0.999) p=0.048, and maternal age OR 1.114 (1.031,
      1.204) p=0.006. CONCLUSION: Leiden mutation of factor V is not an important
      factor for our Mexican mestizo population; however, there are other important
      perinatal risk factors.

PMID- 22587600
TI  - Association of MMP3-1171(5A>6A) polymorphism with lung cancer in Lebanon.
AB  - Matrix metalloproteinases (MMPs) are a family of enzymes that degrade
      extracellular matrix components and are involved in the development and
      progression of cancer. Lung cancer is the most commonly diagnosed cancer in
      Lebanon. This study was undertaken to investigate the association between 
      1171(5A>6A) polymorphism in the promoter of MMP3 gene and the susceptibility to
      lung cancer in a Lebanese population. The MMP3 polymorphism was investigated in
      41 lung cancer patients and 51 unrelated healthy controls using polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) technique. We found
      a significant association between MMP3-1171 5A allele and lung cancer (Odds ratio
      [OR]=2.7, 95% [CI]=1.3-5.3; Fisher's p-value=0.005). This study may form an
      additional evidence for the association of MMP3 enzyme and genetic susceptibility
      to lung cancer.

PMID- 22587601
TI  - Prevalence of psychiatric disorders before and 1 year after bariatric surgery:
      the role of shame in maintenance of psychiatric disorders in patients undergoing
      bariatric surgery.
AB  - OBJECTIVE: The present study examined prevalence of psychiatric disorders before
      and 1 year after weight loss surgery. Furthermore, we studied if level of pre
      operative shame could be a maintaining factor for psychiatric disorders at 1-year
      follow-up. METHOD: One-hundred and twenty-seven patients (F/M: 94/33) with mean
      body mass index (BMI) +/- standard deviation (s) =45.3+/-5.2 kg/m(2) and mean age
      41.3+/-10.3 years participated in the study. Eighty-seven patients met for follow
      up 1 year after surgery. Psychiatric disorders were assessed by the Mini
      International Neuropsychiatric Interview (M.I.N.I.) and the Structured Clinical
      Interview (SCID-II). Levels of depression, anxiety and shame were assessed by the
      Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAI) and the
      Internalized Shame Scale (ISS). RESULTS: Sixty-one patients (48%) at pre
      operative assessment and 16 patients (18%) at 1-year follow-up had a comorbid
      psychiatric disorder. The strongest predictor of post-operative psychiatric
      disorder was pre-operative psychiatric disorder, odds ratio of 27.7 (95% CI for
      EXP (B) 3.2-239.8, P =0.003). Pre-operative level of shame (higher than 50-point
      ISS score) was also a significant predictor for post-operative psychiatric
      disorders, odds ratio of 9.1 (95% CI for EXP (B) 1.8-44.4, P =0.007). CONCLUSION:
      There was a significant reduction in prevalence of psychiatric disorders from pre
      operative assessment to follow-up 1 year after surgery. Level of shame at pre
      operative assessment was associated with maintenance of psychiatric problems.
      This finding is of clinical importance, since psychiatric disorders persisting
      after bariatric surgery have strong impact on the course of weight loss and
      quality of life.

PMID- 22587602
TI  - Macrocyclic lactones in antiparasitic therapy. Editorial.

PMID- 22587603
TI  - Dibenzo[c,h][1,5]naphthyridinediones as topoisomerase I inhibitors: design,
      synthesis, and biological evaluation.
AB  - Dibenzo[c,h][1,5]naphthyridinediones were prepared via a novel synthetic pathway.
      The compounds were designed as topoisomerase I (Top1) inhibitors based on the
      indenoisoquinoline series of drugs. The results of biological evaluation
      demonstrate that, unlike very closely related
      dibenzo[c,h][1,6]naphthyridinediones, dibenzo[c,h][1,5]naphthyridinediones retain
      the Top1 inhibitory activity of similarly substituted indenoisoquinolines.

PMID- 22587604
TI  - TIM3 gene polymorphisms in patients with chronic hepatitis B virus infection:
      impact on disease susceptibility and hepatocellular carcinoma traits.
AB  - Hepatitis B virus (HBV) infection is associated with the development of acute and
      chronic liver diseases including hepatocellular carcinoma (HCC). T-cell
      immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3), which
      negatively regulates T-cell response and mediates phagocytosis of apoptotic
      cells, has been implicated in HBV infection and cancers. This study explored the
      polymorphisms of TIM3 gene in 535 patients with HBV-related liver diseases
      including 213 chronic hepatitis, 178 cirrhosis and 144 HCC, 72 HBV infection
      resolvers and 182 healthy controls and analyzed the effects of these
      polymorphisms on the disease susceptibility and HCC traits. TIM3-1541C/T, 
      1516G/T, -882C/T, -574G/T and +4259T/G polymorphisms were genotyped using
      polymerase chain reaction-restriction fragment length polymorphism. Of the five
      polymorphisms genotyped, the allele T-containing genotypes (GT + TT), allele T
      and allele T-containing haplotype (CTCGT) of -1516G/T polymorphism were more
      frequent in HBV patients than in controls [P = 0.005, odds ratio (OR) = 2.300,
      95% confidence interval (CI): 1.294-4.088; P = 0.004, OR = 2.266, 95% CI: 1.297
      3.962; and P = 0.005, OR = 2.203, 95% CI: 1.260-3.854, respectively]. The allele
      T-containing genotypes and allele T of -1516G/T were associated with HCC tumor
      grade (P = 0.023 and P = 0.017, respectively) and lymph node metastasis (P =
      0.024 and P = 0.017, respectively). These findings suggest that -1516G/T
      polymorphism in the promoter region of TIM3 gene may affect the disease
      susceptibility and HCC traits associated with HBV infection, potentially
      supporting the role of Tim-3 in T-cell dysfunction and exhaustion involved in
      persistent HBV infection and HCC development.

PMID- 22587606
TI  - Organocatalytic Dakin oxidation by nucleophilic flavin catalysts.
AB  - Flavin catalysts perform the first organocatalytic Dakin oxidation of electron
      rich arylaldehydes to phenols under mild, basic conditions. Catechols are readily
      prepared, and the oxidation of 2-hydroxyacetophenone was achieved. Aerobic
      oxidation is displayed in the presence of Zn(0) as a reducing agent. This
      reactivity broadens the scope of biomimetic flavin catalysis in the realm of
      nucleophilic oxidations, providing a framework for mechanistic investigations for
      related oxidations, such as the Baeyer-Villiger oxidation and Weitz-Scheffer
      epoxidation.

PMID- 22587607
TI  - Isolation and identification of phlorotannins from Ecklonia stolonifera with
      antioxidant and hepatoprotective properties in tacrine-treated HepG2 cells.
AB  - Four kinds of phlorotannins having antioxidant activity were isolated from the
      ethyl acetate fraction of Ecklonia stolonifera ethanolic extract. The structures
      of the phlorotannins were determined on the basis of spectroscopic evidence,
      including 1D and 2D nuclear magnetic resonance. The isolated phlorotannins showed
      potential radical-scavenging activities against 2,2-diphenyl-1-picrylhydrazyl and
      suppressed the intracellular reactive oxygen species in tacrine-treated HepG2
      cells. Among them, eckol and 2-phloroeckol showed hepatoprotective activity in
      tacrine-treated HepG2 cells; however, phlorofucofuroeckol B and 6,6'-bieckol did
      not show the activity, even though having high antioxidant activity. Both eckol
      and 2-phloroeckol inhibited the expression of Fas-mediated cell-death proteins,
      including tBid, caspase-3, and poly(ADP-ribose) polymerase, and suppressed the
      release of cytochrome c from mitochondria to cytosol in a dose-dependent manner
      in tacrine-treated HepG2 cells. These results suggest that eckol and 2
      phloroeckol are the principal hepatoprotective constituents of the ethyl acetate
      fraction of E. stolonifera ethanolic extract.

PMID- 22587608
TI  - Dissociative addition of water to a main group 13 metal cluster: computational
      study of the reaction of gallium dimer with H2O.
AB  - We have investigated the lowest triplet and singlet potential energy surfaces
      (PESs) for the reaction of Ga(2) dimer with water. Under thermal conditions, we
      predict formation of the triplet ground state addition complex
      Ga(2)...OH(2)((3)B(1)) involving Ga...O...Ga bridge interaction. At the coupled
      cluster CCSD(T)/AE (CCSD(T)/ECP) computational levels, Ga(2)...OH(2)((3)B(1)) is
      bound by 5.5 (5.7) kcal/mol with respect to the ground state reactants
      Ga(2)((3)Pi(u)) + H(2)O. Identification of the addition complex is in agreement
      with the experimental evidence from matrix isolation infrared (IR) spectroscopy
      reported recently by Macrae and Downs. The located minimum energy crossing points
      (MECPs) between the triplet and singlet energy surfaces on the entrance channel
      of Ga(2) + H(2)O are not expected to be energetically accessible under the matrix
      conditions, consistent with the lack of occurrence of Ga(2) insertion into the O
      H bond under such conditions. The computed energies and harmonic and anharmonic
      vibrational frequencies for the triplet and singlet Ga(2)(H)(OH) insertion
      isomers indicate the singlet double-bridged Ga(MU-H)(MU-OH)Ga isomer to be the
      most stable and support the experimental IR identification of this species. The
      energy barrier for elimination of H(2) from the second most stable singlet HGa(MU
      OH)Ga insertion isomer found to be 13.9 (12.9) kcal/mol is also consistent with
      the available experimental data.

PMID- 22587609
TI  - Proteomic analysis of 17beta-estradiol degradation by Stenotrophomonas
      maltophilia.
AB  - Microbial degradation plays a critical role in determining the environmental fate
      of steroid hormones, such as 17beta-estradiol (E2). The molecular mechanisms
      governing the microbial transformation of E2 and its primary degradation
      intermediate, estrone (E1), are largely unknown. The objective of this study was
      to identify metabolism pathways that might be involved in microbial estrogen
      degradation. To achieve the objective, Stenotrophomonas maltophilia strain ZL1
      was used as a model estrogen degrading bacterium and its protein expression level
      during E2/E1 degradation was studied using quantitative proteomics. During an E2
      degradation experiment, strain ZL1 first converted E2 to E1 stoichiometrically.
      At 16 h E1 reached its peak concentration, and microbial growth started. At the
      same time, enzymes involved in certain catabolic and anabolic pathways were most
      highly expressed compared to the other time points tested. Among those enzymes,
      the ones involved in protein and lipid biosyntheses were observed to be
      particularly active. Based on the metabolite information from a previous study
      and the proteomic data from this study, we hypothesized that S. maltophilia
      strain ZL1 was able to convert E1 to amino acid tyrosine through ring cleavage on
      a saturated ring of the E1 molecule and then utilize tyrosine in protein
      biosynthesis.

PMID- 22587611
TI  - The aging of the donor base.

PMID- 22587610
TI  - Impact of oral simvastatin therapy on acute lung injury in mice during
      pneumococcal pneumonia.
AB  - BACKGROUND: Recent studies suggest that the reported protective effects of
      statins (HMG-CoA reductase inhibitors) against community-acquired pneumonia (CAP)
      and sepsis in humans may be due to confounders and a healthy user-effect. To
      directly test whether statins are protective against Streptococcus pneumoniae,
      the leading cause of CAP, we examined the impact of prolonged oral simvastatin
      therapy at physiologically relevant doses in a mouse model of pneumococcal
      pneumonia. BALB/c mice were placed on rodent chow containing 0 mg/kg (control),
      12 mg/kg (low simvastatin diet [LSD]; corresponds to 1.0 mg/kg/day), or 120 mg/kg
      (high simvastatin diet [HSD]; corresponds to 10 mg/kg/day) simvastatin for four
      weeks, infected intratracheally with S. pneumoniae serotype 4 strain TIGR4, and
      sacrificed at 24, 36, or 42 h post-infection for assessment of lung histology,
      cytokine production, vascular leakage and edema, bacterial burden and bloodstream
      dissemination. Some mice received ampicillin at 12-h intervals beginning at 48 h
      post-infection and were monitored for survival. Immunoblots of homogenized lung
      samples was used to assess ICAM-1 production. RESULTS: Mice receiving HSD had
      reduced lung consolidation characterized by less macrophage and neutrophil
      infiltration and a significant reduction in the chemokines MCP-1 (P = 0.03) and
      KC (P = 0.02) and ICAM-1 in the lungs compared to control mice. HSD mice also had
      significantly lower bacterial titers in the blood at 36 (P = 0.007) and 42 (P =
      0.03) hours post-infection versus controls. LSD had a more modest effect against
      S. pneumoniae but also resulted in reduced bacterial titers in the lungs and
      blood of mice after 42 h and a reduced number of infiltrated neutrophils. Neither
      LSD nor HSD mice had reduced mortality in a pneumonia model where mice received
      ampicillin 48 h after challenge. CONCLUSIONS: Prolonged oral simvastatin therapy
      had a strong dose-dependent effect on protection against S. pneumoniae as
      evidenced by reduced neutrophil infiltration, maintenance of vascular integrity,
      and lowered chemokine production in the lungs of mice on HSD. Statin therapy also
      protected through reduced bacterial burden in the lungs. Despite these protective
      correlates, mortality in the simvastatin-receiving cohorts was equivalent to
      controls. Thus, oral simvastatin at physiologically relevant doses only modestly
      protects against pneumococcal pneumonia.

PMID- 22587612
TI  - Xanthine oxidase inhibition prevents atrial fibrillation in a canine model of
      atrial pacing-induced left ventricular dysfunction.
AB  - AIMS: Oxidative stress could be a possible mechanism and a therapeutic target of
      atrial fibrillation (AF). Xanthine oxidase (XO) inhibition reduces oxidative
      stress, but the effects of XO inhibitor on AF have not been evaluated. Hence, we
      assessed the effects of XO inhibitor, allopurinol, on progression of atrial
      vulnerability in dogs associated with tachycardia-induced cardiomyopathy. METHODS
      AND RESULTS: The dogs were subjected to atrial tachypacing (ATP, 400 bpm) without
      atrioventricular block for 4 weeks. The dynamics of atrial-tachycardia remodeling
      were evaluated in allopurinol-treated dogs (ALO, n = 5), placebo-treated controls
      (CTL, n = 6), and sham-operated dogs (n = 6). In CTL dogs, 4 weeks of ATP
      significantly increased AF duration (DAF; from 0.2 +/- 0.2 seconds to 173 +/- 67
      seconds, P < 0.05) and decreased atrial effective refractory period (ERP; from
      152 +/- 9 milliseconds to 80 +/- 4 milliseconds at a cycle length of 350
      milliseconds, P < 0.01). Allopurinol attenuated the ATP effects on ERP (118 +/- 6
      milliseconds, P < 0.01) or DAF (0.6 +/- 0.3 seconds, P < 0.05). In CTL dogs, ATP
      induced rapid ventricular responses decreased left ventricular ejection fraction
      (LVEF; from 58.6 +/- 0.1 to 23.5 +/- 2.4%, P < 0.01), and increased left atrial
      diameter (LAD; from 17 +/- 1 mm to 24 +/- 1 mm, P < 0.01). ATP increased atrial
      fibrosis when compared with sham-operated dogs (CTL 10.7 +/- 0.8% vs Sham 1.1 +/-
      0.3%, P < 0.01). Allopurinol suppressed atrial fibrosis (2.3 +/- 0.6%, P < 0.01
      vs CTL) and eNOS reduction without affecting LVEF (20.6 +/- 2.2%, ns) and LAD (23
      +/- 1 mm, ns). CONCLUSION: Allopurinol suppresses AF promotion by preventing both
      electrical and structural remodeling. These results suggest that XO may play an
      important role in enhancement of atrial vulnerability, and might be a novel
      target of AF therapy.

PMID- 22587613
TI  - De novo DNA methylation activity of methyltransferase 1 (MET1) partially restores
      body methylation in Arabidopsis thaliana.
AB  - Arabidopsis METHYLTRANSFERASE 1 (MET1) controls faithful maintenance of cytosine
      methylation at CG sites in repetitive regions and central body regions of active
      genes. If MET1 is removed in a mutant background, CG methylation is lost and is
      only restored in specific heterochromatic regions that have maintained competence
      for re-methylation due to the presence of small RNAs and the RNA-directed DNA
      methylation pathway that controls de novo DNA methylation functions. We analysed
      re-methylation at a locus that loses body methylation in an met1 mutant. We found
      that body methylation at this locus is at least partially restored when MET1 is
      re-introduced into the met1 mutant background, either via genetic cross or DNA
      transfer. Re-methylation is region-specific but random with respect to individual
      CG targets, does not require passage through the germline, and its efficiency
      appears to be influenced by transcription. This suggests that, at least at some
      loci, MET1 has de novo methylation activity that can restore lost body
      methylation patterns. We propose that this activity helps to stabilize body
      methylation patterns, and the random target site selection probably also enhances
      the variability of body methylation patterns.

PMID- 22587614
TI  - Hydrogels containing redispersible spray-dried melatonin-loaded nanocapsules: a
      formulation for transdermal-controlled delivery.
AB  - The aim of the present study was to develop a transdermal system for controlled
      delivery of melatonin combining three strategies: nanoencapsulation of melatonin,
      drying of melatonin-loaded nanocapsules, and incorporation of nanocapsules in a
      hydrophilic gel. Nanocapsules were prepared by interfacial deposition of the
      polymer and were spray-dried using water-soluble excipients. In vitro drug
      release profiles were evaluated by the dialysis bag method, and skin permeation
      studies were carried out using Franz cells with porcine skin as the membrane. The
      use of 10% (w/v) water-soluble excipients (lactose or maltodextrin) as spray
      drying adjuvants furnished redispersible powders (redispersibility index
      approximately 1.0) suitable for incorporation into hydrogels. All formulations
      showed a better controlled in vitro release of melatonin compared with the
      melatonin solution. The best controlled release results were achieved with
      hydrogels prepared with dried nanocapsules (hydrogels > redispersed dried
      nanocapsules > nanocapsule suspension > melatonin solution). The skin permeation
      studies demonstrated a significant modulation of the transdermal melatonin
      permeation for hydrogels prepared with redispersible nanocapsules. In this way,
      the additive effect of the different approaches used in this study
      (nanoencapsulation, spray-drying, and preparation of semisolid dosage forms)
      allows not only the control of melatonin release, but also transdermal
      permeation.

PMID- 22587615
TI  - Gestational trophoblastic disease: an overview.
AB  - This article reviews the different disease entities that fall under the
      classification of gestational trophoblastic disease (GTD). The conditions
      included range from molar pregnancy to the malignant forms of gestational
      trophoblastic neoplasm (GTN). These disorders all arise from abnormal placental
      trophoblastic development. The different types of GTD, symptomatology, and
      diagnostic modalities are examined. The various methods of treatment are
      reviewed. Although the management of GTD and GTN falls outside the scope of
      midwifery practice, midwives need to be aware of the incidence, risk factors, and
      symptoms for specific types of GTD in order to be able to diagnose and refer for
      treatment in a timely manner. Psychosocial aspects that affect the woman who has
      not only had a pregnancy loss but also may be faced with a life-threatening
      illness are examined. The role of the midwife in the management, counseling, and
      follow-up of GTD and GTN is discussed.

PMID- 22587617
TI  - Isolation and functional characterization of bacterial endophytes from Carica
      papaya fruits.
AB  - AIMS: To isolate and characterize the endophytes from papaya fruits and to
      determine the fermentative potential of the strains. METHODS AND RESULTS:
      Endophytes provide potential sources for novel natural products for the use in
      agriculture and nutrition. There is very limited information on isolation and
      characterization of bacterial endophytes from papaya. We describe isolation and
      characterization of eighteen endophytes of papaya fruit from four economically
      important papaya varieties viz 'Red lady', 'Solo', 'Coorg Honey' and 'Bangalore'.
      The phylogenetic analysis based on the 16S rRNA sequence revealed that isolated
      endophytes are genetically distinct and cluster as discrete clades in the
      dendrogram. The Bacillus species is a predominant bacterial endophyte across
      papaya varieties. The seeds and the endocarp of papaya fruits harbour Kocuria,
      Acinetobacter and Enterobacter species. The Staphylococcus species were detected
      in the fruit mesocarp of two papaya varieties used in the study. The endophytes
      isolated from papaya fruits were capable of producing extracellular enzymes like
      amylase, cellulase, pectinase and xylanase. Three isolates, Bacillus (PE-LR-1 and
      PE-LR-3) and Kocuria (PE-LR-2), were selected for fruit fermentation, and
      antioxidant potential of the fermented product was evaluated. PE-LR-3 fermented
      product has the free radical scavenging activity of 61.2% and a microbial
      cocktail of PE-LR-3 with Saccharomyces cerevisiae MTCC 2918 enhances the
      antioxidant potential to 75.7%. CONCLUSION: These findings suggest that different
      parts of papaya fruits harbour an array of bacterial endophytes that could be
      important agents in attributing the high nutritive status to the fruit and can
      serve as potent microbial cocktails for developing value-added fermented products
      of this important fruit. SIGNIFICANCE AND IMPACT OF STUDY: This study describes
      isolation of a bacterial endophyte from papaya fruit that is capable of improving
      the antioxidant potential of raw papaya after fermentation.

PMID- 22587616
TI  - Associations between retinol-binding protein 4 and cardiometabolic risk factors
      and subclinical atherosclerosis in recently postmenopausal women: cross-sectional
      analyses from the KEEPS study.
AB  - BACKGROUND: The published literature regarding the relationships between retinol
      binding protein 4 (RBP4) and cardiometabolic risk factors and subclinical
      atherosclerosis is conflicting, likely due, in part, to limitations of frequently
      used RBP4 assays. Prior large studies have not utilized the gold-standard western
      blot analysis of RBP4 levels. METHODS: Full-length serum RBP4 levels were
      measured by western blot in 709 postmenopausal women screened for the Kronos
      Early Estrogen Prevention Study. Cross-sectional analyses related RBP4 levels to
      cardiometabolic risk factors, carotid artery intima-media thickness (CIMT), and
      coronary artery calcification (CAC). RESULTS: The mean age of women was 52.9 (+/-
      2.6) years, and the median RBP4 level was 49.0 (interquartile range 36.9-61.5)
      MUg/mL. Higher RBP4 levels were weakly associated with higher triglycerides (age,
      race, and smoking-adjusted partial Spearman correlation coefficient = 0.10; P =
      0.01), but were unrelated to blood pressure, cholesterol, C-reactive protein,
      glucose, insulin, and CIMT levels (all partial Spearman correlation coefficients
      <=0.06, P > 0.05). Results suggested a curvilinear association between RBP4
      levels and CAC, with women in the bottom and upper quartiles of RBP4 having
      higher odds of CAC (odds ratio [95% confidence interval] 2.10 [1.07-4.09], 2.00
      [1.02-3.92], 1.64 [0.82-3.27] for the 1st, 3rd, and 4th RBP4 quartiles vs. the
      2nd quartile). However, a squared RBP4 term in regression modeling was non
      significant (P = 0.10). CONCLUSIONS: In these healthy, recently postmenopausal
      women, higher RBP4 levels were weakly associated with elevations in triglycerides
      and with CAC, but not with other risk factors or CIMT. These data using the gold
      standard of RBP4 methodology only weakly support the possibility that
      perturbations in RBP4 homeostasis may be an additional risk factor for
      subclinical coronary atherosclerosis. TRIAL REGISTRATION: ClinicalTrials.gov
      number NCT00154180.

PMID- 22587618
TI  - Improvement of skin quality using a new collagen scaffold in acute burns and
      reconstructive surgery: an in vivo evaluation of split skin graft transplantation
      in a rat model.
AB  - INTRODUCTION: Split-thickness skin grafting is often associated with poor skin
      quality. In this context, a new collagen cell carrier (CCC), as an underlayment
      in split skin graft (SSG) transplantation for covering tissue defects in rats,
      has been evaluated as an improving agent. METHODS: Twenty-eight full-thickness
      wounds were covered with SSGs, applying the CCC as an underlayment in 14 rats and
      using SSG transplantation alone in control group. Postgraft skin areas were
      assessed using an instrument that measures mechanical properties of skin. Three
      parameters were considered for skin elasticity analysis: total skin deviation
      (R0), gross elasticity (R2) and viscoelasticity (R8). Measurements were performed
      every 10 days for 80 days after grafting. Biopsies were taken subsequently for
      histologic evaluation. RESULTS: The results demonstrated significantly superior
      elasticity values in CCC-supplemented SSGs in terms of gross elasticity and
      viscoelasticity (R2/R8) starting from day 60 after grafting to the end of the
      measuring period. There was no histologic evidence of inflammation, adverse host
      tissue reaction, or scar tissue formation. CONCLUSION: Split skin grafting is
      associated with poor dermal quality, but CCC may offer unique opportunities in
      complex wound management in terms of skin graft quality improvement.

PMID- 22587619
TI  - Copper-mediated oxidative cross-coupling reaction of terminal alkynes with alpha
      silyldifluoromethylphosphonates: an efficient method for alpha,alpha
      difluoropropargylphosphonates.
AB  - A copper-mediated oxidative cross-coupling reaction of terminal alkynes with
      readily available alpha-silyldifluoromethylphosphonates under mild conditions has
      been developed. This method allows for an efficient synthesis of a series of
      synthetically useful alpha,alpha-difluoropropargylphosphonates with excellent
      functional group compatibility.

PMID- 22587620
TI  - More functional genes and convergent overall functional patterns detected by
      GEOCHIP in phenanthrene-spiked soils.
AB  - To explore the effect of phenanthrene on the functional diversity of soil
      microbial communities, Luvisol and Cambisol spiked with phenanthrene and their
      corresponding control soils were incubated in soil microcosms. Total community
      DNA extracted from samples taken at days 0 and 21 was analyzed by geochip. The
      number of genes detected by geochip was unexpectedly higher in spiked soils than
      in control soils, especially for Luvisol. Enriched genes in the spiked Luvisol
      were mainly affiliated to proteobacterial and actinobacterial genes involved in
      the degradation of aromatic compounds, heavy metal resistance, sulfate reduction,
      nitrogen and carbon cycling, suggesting changes in the relative abundance of
      these aerobic and anaerobic functional groups after phenanthrene spiking.
      Interestingly, the overall functional gene patterns in the different soils
      converged after phenanthrene spiking, indicating the selection of similar
      functional groups.

PMID- 22587621
TI  - A grounded theory of taking control after fall-induced hip fracture.
AB  - PURPOSE: We applied the grounded theory method to explore the post discharge
      concerns of older people after fall-induced hip fracture repair. It was
      anticipated that this understanding would increase awareness of issues that may
      impact on recovery and rehabilitation. METHOD: Semi-structured interviews were
      carried out with 19 older people after discharge home. Initially, purposive
      sampling guided data collection and thereafter theoretical sampling was employed.
      Interviews were analysed using the constant comparative method. RESULTS: We
      generated a theory of how older people 'take control' after hip fracture.
      Conceptually, taking control was about 'balancing' and was both a process and a
      range of strategies. The three stages of the process that people moved through
      were: 'going under', 'keeping afloat' and 'gaining ground'. Nautical metaphors
      conceptualise the precarious and unstable conditions that older people faced as
      they struggled to regain their independence. Older people struggled to balance
      help and risk, in their attempt to manage their concerns relating to losing
      control of their future independence. CONCLUSION: Older people are vulnerable to
      losing a sense of control after a health trauma. This theory adds a new dimension
      to our understanding of recovery from hip fracture and highlights that older
      people and their families need tailored information and support to enable them to
      take control safely and appropriately.

PMID- 22587622
TI  - Collaboration at the federal, state, and local levels to build capacity in
      maternal and child health: the impact of the Maternal and Child Health
      Epidemiology Program.
AB  - This article provides a description of the Maternal and Child Health Epidemiology
      Program housed in the Division of Reproductive Health at the Centers for Disease
      Control and Prevention. The article highlights programmatic efforts to build
      capacity and increase infrastructure within states, localities, and among tribes
      in the field of maternal and child health by leveraging partnerships with other
      federal, nonprofit, private, and academic agencies.

PMID- 22587623
TI  - Scanning electrochemical microscopy study of ion annihilation electrogenerated
      chemiluminescence of rubrene and [Ru(bpy)3]2+.
AB  - Scanning electrochemical microscopy (SECM) was used for the study of
      electrogenerated chemiluminescence (ECL) in the radical annihilation mode. The
      concurrent steady-state generation of radical ions in the microgap formed between
      a SECM probe and a transparent microsubstrate provides a distance-dependent ECL
      signal that can provide information about the kinetics, stability, and mechanism
      of the light emission process. In the present study, the ECL emission from
      rubrene and [Ru(bpy)(3)](2+) was used to model the system by carrying out
      experiments with the SECM and light-detecting apparatus inside an inert
      atmosphere box. We studied the influence of the distance between the two
      electrodes, d, and the annihilation kinetics on the ECL light emission profiles
      under steady-state conditions, as well as the ECL profiles when carrying out
      cyclic voltammetry (CV) at a fixed d. Experimental results are compared to
      simulated results obtained through commercial finite element method software. The
      light produced by annihilation of the ions was a function of d; stronger light
      was observed at smaller d. The distance dependence of the ECL emission allows the
      construction of light approach curves in a similar fashion as with the tip
      currents in the feedback mode of SECM. These ECL approach curves provide an
      additional channel to describe the reaction kinetics that lead to ECL; good
      agreement was found between the ECL approach curve emission profile and the
      simulated results for a fast, diffusion-limited second-order annihilation process
      (k(ann) > 10(7) M(-1) s(-1)). In the CV mode at fixed distance, the ECL emission
      of rubrene showed two distinct signals at different potentials when fixing the
      substrate to generate the radical cation and scanning the tip to generate the
      radical anion. The first signal (pre-emission) corresponded to an emission well
      before reaching the generation of the radical anion and was more intense on Au
      than on Pt. The second ECL signal showed the expected steady-state behavior from
      the second-order annihilation reaction and agreed well with the simulation. A
      comparison of the emission obtained with rubrene and [Ru(bpy)(3)](2+) to test the
      direct formation of lower energy triplets directly at the electrode showed that
      triplets are not the cause of the pre-emission observed. Wavelength selection
      experiments for the rubrene system showed that the pre-emission ECL signal also
      appeared slightly red-shifted with respect to the main luminophore emission; a
      possible explanation for this phenomenon is inverse photoemission, where the
      injection of highly energetic holes by the oxidized species into the negatively
      biased tip electrode causes emission of states in the metal that appear at a
      different wavelength than the singlet emission from the ECL luminophore.

PMID- 22587624
TI  - A new scale for assessment of severity and outcome in iNPH.
AB  - OBJECTIVE: To present a new, continuous, calibrated and norm-based scale for the
      grading of severity and assessment of treatment outcome in idiopathic normal
      pressure hydrocephalus (iNPH). PATIENTS AND METHODS: A scale designed for the
      assessment of the four domains, gait, neuropsychology, balance and continence,
      using ordinal ratings and continuous measures, was developed. Data from a series
      of 181 consecutive iNPH patients were used to calibrate the continuous parts of
      the scale and to describe the distributional properties of the ordinal ratings.
      Data from normative studies were used to determine the limits for normal scores.
      RESULTS: The construction of the scale made it well equipped to separate iNPH
      patients at baseline, and the total scores assumed a bell-shaped, approximately
      normal distribution. All four domain scores correlated significantly with each
      other, underscoring the well-known syndromatic nature of iNPH, and justifying the
      use of a total score to describe the patients. Reliability [Cronbach's alpha for
      the total score = 0.74, and for the domains of gait and neuropsychology, 0.86 and
      0.89, respectively) and validity estimates (convergent validity evaluated by
      Spearman rank correlations for the scale and the modified Rankin scale (rho = 
      0.61) and the mini mental state examination (rho = 0.57)] are satisfying.
      CONCLUSION: The iNPH scale covers the four most important symptom domains and the
      full range of severity of the iNPH syndrome. The scale is sensitive, reliable,
      valid and feasible. We recommend that it should be used in future iNPH research.

PMID- 22587625
TI  - Accumulation of phenylpropanoids and correlated gene expression during the
      development of tartary buckwheat sprouts.
AB  - Buckwheat sprouts are considered an excellent dietary source of phenolic
      compounds. The time duration and amount of light for sprouting strongly affect
      the nutritional quality of sprouts. In this study, these two factors were
      investigated in two cultivars of tartary buckwheat sprouts: Hokkai T8 and T10.
      The transcriptional levels of flavonoid biosynthetic genes were investigated in
      light/dark- and dark-treated sprouts. Among the main flavonoid biosynthesis
      structural genes, FtPAL, Ft4CL, FtF3H, FtDFR, and FtANS exhibited higher
      transcriptional levels than others as compared to that of a housekeeping gene
      (histone H3) during sprouting; FtF3'H1, FtF3'H2, FtFLS2, and FtANS were
      substantially upregulated at 2, 4, and 6 days in light/dark-treated T10 sprouts
      than in dark-treated ones. However, FtDFR was downregulated in 8 and 10 day old
      light/dark-treated sprouts of both cultivars. High-performance liquid
      chromatography (HPLC) analysis revealed that increasing the culture time did not
      affect the accumulation of flavonoids or anthocyanins. However, light contributed
      the production of anthocyanins in Hokkai T10 sprouts. The anthocyanins included
      cyanidin 3-O-glucoside, cyanidin 3-O-rutinoside, and delphinidin-3-O
      coumarylglucoside, which were identified by HPLC and electrospray ionization
      tandem mass spectrometry. Instead of anthocyanins, Hokkai T8 sprouts produced
      large amounts of 4 flavonoid C-glycosylflavone compounds in both light/dark and
      dark conditions: orientin, isoorientin, vitexin, and isovitexin. These results
      indicate that these two types of tartary buckwheat sprouts have different
      mechanisms for flavonoid and anthocyanin biosynthesis that also vary in
      light/dark and dark conditions.

PMID- 22587626
TI  - Improvement of refractory migraine headache by propofol: case series.
AB  - BACKGROUND: Several studies have been conducted on managing migraine headaches
      and developing effective medications for decreasing migraine-associated pain.
      CASE PRESENTATION: Intravenous propofol was prescribed (10 mg every 5 min) for
      eight patients with intractable migraine headaches visiting the Emergency
      Department. The average pain score experienced by patients was recorded using the
      Visual Analogue Scale at the beginning of the treatment procedure and following
      the injection for 30 min (5-min intervals). The patients' reported pain scores
      decreased significantly (P = 0.01) from 8.87 +/- 0.83 (CI: 8.17, 9.57) to 1.12 +/
      0.83 (CI: 0.43, 1.82) before and 30 min following the injection. DISCUSSION: It
      seems that in the treatment of intractable migraine headaches, GABAergic
      receptors, compared to the normal conditions, have a lower activity status.
      CONCLUSION: Because of the high tendency of propofol to GABAergic receptors, it
      probably changes this physiological condition by activating the receptors, which
      results in a significant pain reduction.

PMID- 22587627
TI  - Impact of patient-prosthesis mismatch on 30-day outcomes in young and middle-aged
      patients undergoing aortic valve replacement.
AB  - BACKGROUND: The impact of patient-prosthesis mismatch (PPM) on early outcomes in
      young and middle-aged patients undergoing conventional aortic valve replacement
      for severe aortic stenosis remains unknown. Our objective was to evaluate the
      incidence of some degree of PPM and its influence on early mortality and
      morbidity. METHODS: We analyzed our single center experience in all patients <70
      years undergoing first-time isolated aortic valve replacement for severe stenosis
      in our center from September 2007 to September 2011. PPM was defined as an
      indexed effective orifice area <= 0,85 cm(2)/m(2). The influence of PPM on early
      mortality and postoperative complications was studied using propensity score
      analysis. Follow up at 30 postoperative days was 100% complete. RESULTS: Of 199
      patients studied, 61 (30,7%) had some degree of PPM. PPM was associated with an
      increased postoperative mortality (OR = 8,71; 95% CI = 1,67-45,29; p = 0,04) and
      major postoperative complications (OR = 2,96; CI = 1,03-8,55; p = 0,044).
      However, no association between PPM and prolonged hospital or ICU stay was
      demonstrated. CONCLUSIONS: Moderate PPM is a common finding in young and middle
      aged patients undergoing surgery for aortic valve replacement due to severe
      stenosis. In addition, its influence on early outcomes may be relevant.

PMID- 22587628
TI  - Increased risk of ovarian hyperstimulation syndrome following controlled ovarian
      hyperstimulation in patients with vascular endothelial growth factor +405 cc
      genotype.
AB  - Ovarian hyperstimulation syndrome (OHSS) is a serious complication following
      controlled ovarian hyperstimulation (COH) for in vitro fertilization. OHSS has a
      range of clinical features from mild abdominal distention to severe
      thromboembolic events. Several clinical manifestations of OHSS such as ascites
      and hemoconcentration can be attributed to increased vascular permeability.
      Vascular endothelial growth factor (VEGF) and its receptor VEGFR2 have been
      identified as an important signaling system in mediating this increase. There is
      considerable genetic variation in the VEGF/R2 signaling system. We present the
      first study to examine if single nucleotide polymorphisms (SNPs) in the genes
      encoding the VEGF/R2 signaling system are associated with OHSS following COH.
      Blood samples from 53 OHSS patients and 100 controls were analyzed for six SNPs
      of interest. Odds ratios (OR) and 95% confidence intervals (95% CI) were
      estimated by a multivariate logistic regression model. We found an association
      between the VEGF +405cc genotype and OHSS (OR 3.4, 95% CI 1.01-11.7). This
      finding requires confirmation from other patient populations.

PMID- 22587629
TI  - Sleep duration and sleep quality are associated differently with alterations of
      glucose homeostasis.
AB  - AIMS: Studies suggest that inadequate sleep duration and poor sleep quality
      increase the risk of impaired glucose regulation and diabetes. However,
      associations with specific markers of glucose homeostasis are less well
      explained. The objective of this study was to explore possible associations of
      sleep duration and sleep quality with markers of glucose homeostasis and glucose
      tolerance status in a healthy population-based study sample. METHODS: The study
      comprised 771 participants from the Danish, population-based cross-sectional
      'Health2008' study. Sleep duration and sleep quality were measured by self
      report. Markers of glucose homeostasis were derived from a 3-point oral glucose
      tolerance test and included fasting plasma glucose, 2-h plasma glucose, HbA(1c),
      two measures of insulin sensitivity (the insulin sensitivity index(0,120) and
      homeostasis model assessment of insulin sensitivity), the homeostasis model
      assessment of beta-cell function and glucose tolerance status. Associations of
      sleep duration and sleep quality with markers of glucose homeostasis and
      tolerance were analysed by multiple linear and logistic regression. RESULTS: A 1
      h increment in sleep duration was associated with a 0.3 mmol/mol (0.3%) decrement
      in HbA(1c) and a 25% reduction in the risk of having impaired glucose regulation.
      Further, a 1-point increment in sleep quality was associated with a 2% increase
      in both the insulin sensitivity index(0,120) and homeostasis model assessment of
      insulin sensitivity, as well as a 1% decrease in homeostasis model assessment of
      beta-cell function. CONCLUSIONS: In the present study, shorter sleep duration was
      mainly associated with later alterations in glucose homeostasis, whereas poorer
      sleep quality was mainly associated with earlier alterations in glucose
      homeostasis. Thus, adopting healthy sleep habits may benefit glucose metabolism
      in healthy populations.

PMID- 22587630
TI  - Catheter ablation for idiopathic right ventricular outflow tract premature
      ventricular contraction via the single right transjugular approach.

PMID- 22587631
TI  - Novel functionalized nano-TiO2 loading electrocatalytic membrane for oily
      wastewater treatment.
AB  - Membrane fouling is a critical problem in membrane filtration processes for water
      purification. Electrocatalytic membrane reactor (ECMR) was an effective method to
      avoid membrane fouling and improve water quality. This study focuses on the
      preparation and characterization of a novel functionalized nano-TiO(2) loading
      electrocatalytic membrane for oily wastewater treatment. A TiO(2)/carbon membrane
      used in the reactor is prepared by coating TiO(2) as an electrocatalyst via a sol
      gel process on a conductive microporous carbon membrane. In order to immobilize
      TiO(2) on the carbon membrane, the carbon membrane is first pretreated with
      HNO(3) to generate the oxygen-containing functional groups on its surface. X-ray
      diffraction (XRD), field-emission scanning electron microscopy (FESEM), high
      resolution transmission electron microscopy (HRTEM), and X-ray photoelectron
      spectroscopy (XPS) analyses are used to evaluate the morphology and
      microstructure of the membranes. Cyclic voltammetry (CV) and electrochemical
      impedance spectroscopy (EIS) measurements are employed to illustrate the
      eletrochemical activity of the TiO(2)/carbon membrane. The membrane performance
      is investigated by treating oily wastewater. The oil removal rate increases with
      a decrease in the liquid hourly space velocity (LHSV) through the ECMR. The COD
      removal rate was 100% with a LHSV of 7.2 h(-1) and 87.4% with a LHSV of 21.6 h(
      1) during the treatment of 200 mg/L oily water. It suggests that the synergistic
      effect of electrocatalytic oxidation and membrane separation in the ECMR plays a
      key role.

PMID- 22587632
TI  - iTRAQ-based proteomic profiling of breast cancer cell response to doxorubicin and
      TRAIL.
AB  - Breast cancer is a molecularly heterogeneous disease, and predicting response to
      chemotherapy remains a major clinical challenge. To minimize adverse side-effects
      or cumulative toxicity in patients unlikely to benefit from treatment, biomarkers
      indicating treatment efficacy are critically needed. iTRAQ labeling coupled with
      multidimensional LC-MS/MS of the enriched mitochondria and endoplasmic reticulum
      fraction, key organelles regulating apoptosis, has led to the discovery of
      several differentially abundant proteins in breast cancer cells treated with the
      chemotherapeutic agent doxorubicin followed by the death receptor ligand, TRAIL,
      among 571 and 801 unique proteins identified in ZR-75-1 and MDA-MB-231 breast
      cancer cell lines, respectively. The differentially abundant proteins represent
      diverse biological processes associated with cellular assembly and organization,
      molecular transport, oxidative stress, cell motility, cell death, and cancer.
      Despite many differences in molecular phenotype between the two breast cancer
      cell lines, a comparison of their subproteomes following drug treatment revealed
      three proteins displaying common regulation: PPIB, AHNAK, and SLC1A5. Changes in
      these proteins, detected by iTRAQ, were confirmed by immunofluorescence,
      visualized by confocal microscopy. These novel potential biomarkers may have
      clinical utility for assessing response to cancer treatment and may provide
      insight into new therapeutic targets for breast cancer.

PMID- 22587633
TI  - Study of specific ion-amino acid interactions through the use of local
      correlation methods.
AB  - Specific ion effects, related to the hydration of ions and ion-solute
      interactions, play a fundamental part in many processes in chemistry and biology.
      Although intensively studied since the seminal studies of Franz Hofmeister and co
      workers, their molecular origin has only recently started to be unveiled. In this
      work, we have investigated the interaction between halide anions and a selected
      set of amino acid residues in an attempt to identify the forces behind ion
      specificity. Two-dimensional potential energy surfaces have been calculated with
      the use of local second order Moller-Plesset perturbation theory (LMP2), coupled
      with the COSMO model to describe solvent effects. The results show in great
      detail the impact of dispersion interactions, in particular for the heavier
      anions (Br(-) and I(-)). The obtained potential energy surfaces also hint at a
      greater mobility of iodide in the vicinity of a residue, which correlates well
      with its placing in the Hofmeister series.

PMID- 22587635
TI  - Predictive value of symptoms for quality of life in first-episode schizophrenia.
AB  - BACKGROUND: Management of the disease symptomatology impacts the long-term
      functioning and quality of life (QOL) in psychotic patients. AIM: The aim of this
      research was to study the association between psychiatric symptoms (positive,
      negative and general psychopathology symptoms) and QOL in first-episode
      schizophrenia patients. METHODS: Fifty-five first-episode drug-naive
      schizophrenia outpatients were recruited from a tertiary care hospital in New
      Delhi, India. WHOQOL-Bref (World Health Organization Quality of Life) Scale was
      used to assess multi-dimensional domains of QOL (physical, psychological, social
      and environmental health). The patients were evaluated clinically using PANSS and
      followed up for 6 months. Multivariate analyses were carried out to outline the
      symptoms which are predictive of QOL in these patients. RESULTS: Physical well
      being as assessed with WHOQOL-Bref is significantly impacted by the positive,
      negative and general psychopathology symptoms of the disease. General
      psychopathology symptoms demonstrated a strong relationship with different facets
      of QOL. These symptoms are predictive of physical (P=0.025) and psychological
      health (P=0.026), social relationships (P=0.009) and environmental QOL (P=0.022).
      CONCLUSIONS: The general psychopathology symptoms significantly impact QOL in a
      diverse manner. Negative symptoms have a greater influence than positive symptoms
      on subjective QOL. CLINICAL IMPLICATIONS: The antipsychotics focus on primary
      positive and negative disease symptoms. There is a need to develop a holistic
      approach (target non-psychotic symptoms intensively) in the disease management to
      prevent further long-term impairment of QOL.

PMID- 22587634
TI  - A comparative genomics screen identifies a Sinorhizobium meliloti 1021 sodM-like
      gene strongly expressed within host plant nodules.
AB  - BACKGROUND: We have used the genomic data in the Integrated Microbial Genomes
      system of the Department of Energy's Joint Genome Institute to make predictions
      about rhizobial open reading frames that play a role in nodulation of host
      plants. The genomic data was screened by searching for ORFs conserved in alpha
      proteobacterial rhizobia, but not conserved in closely-related non-nitrogen
      fixing alpha-proteobacteria. RESULTS: Using this approach, we identified many
      genes known to be involved in nodulation or nitrogen fixation, as well as several
      new candidate genes. We knocked out selected new genes and assayed for the
      presence of nodulation phenotypes and/or nodule-specific expression. One of these
      genes, SMc00911, is strongly expressed by bacterial cells within host plant
      nodules, but is expressed minimally by free-living bacterial cells. A strain
      carrying an insertion mutation in SMc00911 is not defective in the symbiosis with
      host plants, but in contrast to expectations, this mutant strain is able to out
      compete the S. meliloti 1021 wild type strain for nodule occupancy in co
      inoculation experiments. The SMc00911 ORF is predicted to encode a "SodM-like"
      (superoxide dismutase-like) protein containing a rhodanese sulfurtransferase
      domain at the N-terminus and a chromate-resistance superfamily domain at the C
      terminus. Several other ORFs (SMb20360, SMc01562, SMc01266, SMc03964, and the
      SMc01424-22 operon) identified in the screen are expressed at a moderate level by
      bacteria within nodules, but not by free-living bacteria. CONCLUSIONS: Based on
      the analysis of ORFs identified in this study, we conclude that this comparative
      genomics approach can identify rhizobial genes involved in the nitrogen-fixing
      symbiosis with host plants, although none of the newly identified genes were
      found to be essential for this process.

PMID- 22587636
TI  - Old ideals and new realities: the changing context of young people's partnerships
      in Cebu, Philippines.
AB  - The Philippines has experienced rapid sociodemographic changes in recent years,
      with implications for young people. This study combines quantitative and
      qualitative data from Metro Cebu to assess the timing and predictors of young
      people's partnerships, as well as the context in which these partnerships are
      occurring. The majority of young people (54%) had premarital sex, though this
      pattern varied by gender. Wealthier, urban young men, and women with less
      education and lower reported religiosity, were more likely to have premarital
      sex. Engagement in risk behaviours was predictive of premarital sex for both
      males and females. The qualitative data contextualise the circumstances under
      which young people engage in sex and form partnerships and illustrate how
      sociocultural norms contribute to gender differences in partnership patterns.
      Given the 'new' realities of young Filipinos' lives, targeted efforts to support
      the transition to adulthood are needed to avert potentially adverse life events.

PMID- 22587637
TI  - Multicenter evaluation of a commercial multiplex polymerase chain reaction test
      for screening plasma donations for parvovirus B19 DNA and hepatitis A virus RNA.
AB  - BACKGROUND: Three European laboratories evaluated the TaqScreen DPX test (DPX
      test), a multiplex nucleic acid test assay for the simultaneous detection and
      quantitation of parvovirus B19 (B19V) DNA and the detection of hepatitis A virus
      (HAV) RNA. STUDY DESIGN AND METHODS: The 95% limit of detection of the test for
      B19V and HAV was determined using the respective WHO International Standards. The
      reproducibility of the test was evaluated by testing replicate samples of B19V at
      log 4.0 and 40 IU/mL and HAV at 5 IU/mL. The accuracy of the DPX test for B19V
      was evaluated by replicate testing of B19V samples containing log 3.0, log 4.0,
      and log 5.0 IU/mL. Panels of B19V Genotypes 1, 2, and 3 and HAV genotypes were
      evaluated. Cross-contamination was evaluated. For comparison of the DPX test and
      the established tests, the sites tested plasma samples in pools of either 96 or
      480 donations. RESULTS: The mean 95% lower limits of detection of the three
      laboratories for B19V and HAV were 20.30 and 1.85 IU/mL. The test showed good
      reproducibility with the major part of the variance of the test being attributed
      to intermediate assay variation. The test showed great accuracy for B19V,
      especially at log 4.0 IU/mL. Spiking of test pools of 480 donations and
      manufacturing pools with log 4.0 IU/mL B19 DNA and 4 IU/mL HAV RNA showed that
      the DPX assay was robust. The test was able to detect the three genotypes of B19V
      and HAV genotypes. No cross-contamination was seen. Test results of routine
      samples correlated well with those of the established tests. CONCLUSION: The DPX
      test is a robust and sensitive test for the detection of B19V and HAV in plasma
      samples. The quantitative B19V results obtained with the test are accurate, and
      the test is able to detect all the known genotypes of B19V and HAV and fulfills
      all the European Pharmacopoeia and Food and Drug Administration requirements for
      a B19V and HAV test for screening of plasma donations and samples from plasma
      pools for manufacture.

PMID- 22587638
TI  - Low plasma renin activity and high aldosterone/renin ratio are associated with
      untreated isolated systolic hypertension.
AB  - OBJECTIVE: Isolated systolic hypertension (ISH) is generally encountered in
      elderly patients and there are scarce data regarding the renin-angiotensin
      aldosterone system (RAAS) activity in patients with ISH. We aimed to determine
      the plasma renin activity (PRA), plasma aldosterone levels (PAL) and
      aldosterone/PRA ratio (PAL/PRA) in patients (age >50 years) with ISH and to
      compare these values with patients with essential hypertension (EH) as well as
      subjects with normal blood pressure values (control) who have similar age and
      cardiovascular risk profile. METHODS: Consecutively, 42 untreated ISH patients,
      30 patients with EH and 29 normal subjects were included in the study. Parameters
      were presented as median (interquartile range). RESULTS: There were no
      significant differences regarding age, gender and other cardiovascular risk
      factors among groups. As expected, systolic, diastolic blood pressure and pulse
      pressure values were significantly different among groups. Besides, PRA values
      were found to be significantly lower in patients with ISH (0.4 [0.2-1.1] ng/ml/h)
      compared with the EH (0.95 [0.5-2.6] ng/ml/h, p =0.024) and control (1.3 [0.7
      2.1] ng/ml/h, p =0.001) groups. Although, PAL were similar among groups, PAL/PRA
      ratio was significantly higher in ISH group (134.1 [73-224]) compared with those
      with EH (42.2 [35-84], p <0.001) and the control group (53.3 [30-106], p =0.001).
      No significant difference was present with respect to PAL/PRA ratio between EH
      and control groups. CONCLUSIONS: Our findings suggested that in patients with
      ISH, despite lower PRA levels, PAL/PRA ratio is significantly higher compared
      with the patients with EH and subjects with normal blood pressure. Since higher
      PAL/PRA levels is an indicator of relative aldosterone excess, medications
      blocking RAAS activity including aldosterone antagonists may have useful
      cardiovascular consequences in addition to their antihypertensive effects in ISH.

PMID- 22587639
TI  - Does a screening questionnaire for familial and hereditary colorectal cancer risk
      work in a health insurance population?
AB  - The aim of our study was to evaluate actual prevalence, uptake and first
      experiences with a questionnaire developed for early detection of colorectal
      cancer (CRC) in persons with familial/hereditary risk. A cross sectional study in
      an insurance population aged 30-54 years was conducted. Subjects with ICD-10
      codes C00 to C97 and D37 to D48 were excluded. A standardised questionnaire was
      sent to 12,139 subjects. Three months later, subjects with a reported family
      history were followed by a second questionnaire. An additional telephone survey
      was performed to validate responses. Nineteen per cent met the inclusion criteria
      (mean age 45 +/- 7 years, 38% men). Three hundred and seventy-three subjects
      (16%) were followed by a second questionnaire. Of these, 248 (66%) returned.
      Forty-four per cent were already aware of their increased risk of developing CRC.
      Awareness was associated with knowledge of CRC. One hundred subjects (41%)
      reported that they had informed their general practitioner (GP) or
      gastroenterologist. A colonoscopy or stool test was recommended to 92. Subjects
      who found out about their increased risk for the first time, reported
      significantly less frequent physician contact (GP: 20% vs. 34%,
      gastroenterologist: 8% vs. 21%). Results indicate that there is a need for a
      structured, person at risk-adapted, statutory early detection program.

PMID- 22587640
TI  - Gold nanonetwork film on the ITO surface exhibiting one-dimensional optical
      properties.
AB  - A network of gold nanostructures exhibiting one-dimensional gold nanostructure
      properties may become a prospective novel structure for optical, electrical and
      catalytic applications benefited by its unusual characteristics resulting from
      the collective properties of individual nanostructures in the network. In this
      paper, we demonstrate a facile method for the formation of high-density gold
      nanonetwork film on the substrate surface composed of quasi-1D nanoparticles
      (typically fusiform) with length ca. 10 nm - via reduction of gold ions in the
      presence of nanoseeds attached surface, binary surfactants of
      cetyltrimethylammonium bromide and hexamethyleneteramine and Ag+ ions. The length
      of the nanonetworks can be up to ca. 100 nm, which corresponds to the aspect
      ratio of ca. 10. The quasi-1D gold nanostructures as well as the nanonetworks
      were found to be sensitive to the binary surfactants system and the Ag+ ions as
      they can only be formed if all the chemicals are available in the reaction. The
      nanonetworks exhibit unique 1D optical properties with the presence of transverse
      and longitudinal surface plasmon resonance absorption. Owing to their peculiar
      structures that are composed of small quasi-1D nanoparticles, the nanonetworks
      may produce unusual optical and catalytic properties, which are potentially used
      in surface-enhanced Raman scattering, catalysis and optical and non-linear
      optical applications.

PMID- 22587642
TI  - Custodial grandparents raising grandchildren: lack of legal relationship is a
      barrier for services.
AB  - In the United States, the majority of custodial grandparents are raising their
      grandchildren without a legal relationship. The lack of a legal relationship
      (i.e., foster care, custody, adoption) is a barrier for obtaining services and
      has resulted in limited access to information and public services, inadequate
      financial assistance, and difficulty providing medical and educational consent.
      This situation arises not only as a consequence of eligibility criteria, but also
      because children being raised by custodial grandparents remain outside the child
      welfare system. Federal and state policies were not designed for this population;
      subsequently, the majority of grandparent caregivers remain without access to
      services and support. In this article, perceptions of custodial grandparents
      concerning family obligations and the child welfare system as a barrier to
      pursuing a legal relationship are reviewed. Challenges with existing financial
      and health services, educational needs of grandparents and providers, and
      suggestions for policy changes are presented.

PMID- 22587643
TI  - Validity of the malnutrition screening tool for older adults at high risk of
      hospital readmission.
AB  - Malnutrition is a serious problem in older adults, particularly for those at risk
      of hospital readmission. The essential step in managing malnutrition is early
      identification using a valid nutrition screening tool. The purpose of this study
      was to validate the Malnutrition Screening Tool (MST) in older adults at high
      risk of hospital readmission. Two RNs administered the MST to identify
      malnutrition risk and compared it with the comprehensive Subjective Global
      Assessment (SGA) to assess nutritional status for patients 65 and older who had
      at least one risk factor for hospital readmission. The MST demonstrates
      substantial sensitivity, specificity, and agreement with the SGA. These findings
      indicate that nursing staff can use the MST as a valid tool for routine screening
      and rescreening to identify patients at risk of malnutrition. Use of the MST may
      prevent hospital-acquired malnutrition in acute hospitalized older adults at high
      risk of readmission.

PMID- 22587641
TI  - Improving medication management among at-risk older adults.
AB  - Low health literacy is common among Medicare recipients and affects their
      understanding of complex medication regimens. Interventions are needed to improve
      medication use among older adults, while addressing low health literacy.
      Community-dwelling older adults in this study were enrolled at an inner-city
      adult day center. They completed a baseline measure of health literacy,
      medication self-efficacy, and medication adherence. They were provided with a
      personalized, illustrated daily medication schedule (PictureRxTM). Six weeks
      later, their medication self-efficacy and adherence were assessed. Among the 20
      participants in this pilot project, 70% had high likelihood of limited health
      literacy and took an average of 13.20 prescription medications. Both self
      efficacy and medication adherence increased significantly after provision of the
      PictureRx cards (p < 0.001 and p < 0.05, respectively). All participants rated
      the PictureRx cards as very helpful in terms of helping them remember the
      medication's purpose and dosing. Illustrated daily medication schedules improve
      medication self-efficacy and adherence among at-risk, community-dwelling older
      adults.

PMID- 22587644
TI  - Minimizing health risks among older adults with intellectual and/or developmental
      disabilities: clinical considerations to promote quality of life.
AB  - The number of individuals aging with lifelong intellectual and/or developmental
      disabilities (I/DD) is increasing and is expected to double by 2030. People with
      I/DD have faced a number of health disparities, including health care
      professionals unprepared to meet their health needs. This article will review age
      and health-related clinical considerations among individuals aging with I/DD.
      The aim is to provide nurses with suggested interventions that promote health,
      prevent secondary conditions, and foster person-centered care among individuals
      aging with I/DD to help them live healthy and meaningful lives in their later
      years.

PMID- 22587645
TI  - K2CO3-catalyzed synthesis of chromones and 4-quinolones through the cleavage of
      aromatic C-O bonds.
AB  - Phenol-derived electrophiles are favorable substrates because phenols are
      naturally abundant or can be readily prepared from other aromatic compounds.
      However, the cleavage of aromatic C-O bonds is a great challenge because of their
      high energy. K(2)CO(3)-catalyzed intramolecular cyclization of 1-(2-alkoxyphenyl)
      3-akylpropane-1,3-dione and 3-(alkylimino)-1-(2-methoxyphenyl)-2-methylpropan-1
      one derivatives via the selective cleavage of aromatic C-O bonds is reported. The
      corresponding chromone and 4-quinolone derivatives were obtained in reasonable
      yields.

PMID- 22587646
TI  - Extracorporeal photopheresis, a therapeutic option for cutaneous T-cell lymphoma
      and immunological diseases: state of the art.
AB  - INTRODUCTION: Extracorporeal photopheresis (ECP) has been extensively used for
      the treatment of immune-mediated diseases for over 20 years and has a consistent
      and predictable safety profile with long-term use. Documenting the efficacy of
      ECP as therapeutic treatment has long been a matter of importance for physicians.
      AREAS COVERED: The authors reviewed publications in this field with the goal of
      providing an overview of this therapeutic approach. EXPERT OPINION: ECP is
      efficacious in a high percentage of those cutaneous T-cell lymphoma patients who
      have circulating malignant T cells in the context of a still-near-normal immune
      competence. From the side of graft-versus-host disease (GVHD), the use of ECP
      showed a clinical benefit in patients with steroid-refractory acute GVHD (aGVHD)
      and it is believed that ECP deserves to be evaluated as part of a combination
      strategy in first-line therapy of aGVHD. In chronic GHVD, the published data show
      that ECP can be effective in extensive and long-standing disease even when
      treatment is initiated at an advanced stage after conventional immunosuppressive
      and corticosteroid therapy has failed. ECP should be considered most beneficial
      for patients with predominantly mucocutaneous chronic GVHD. The fields of
      application of the procedure could be vast, and could also include autoimmune and
      metabolic diseases. The most important methodological issues which affect ECP
      evaluation is that the large majority of data about ECP result from single-arm
      observational series and the significant efficacy is mainly based on small and
      retrospective studies. ECP has never been proved to offer any survival advantage
      in a context of a randomized trial and the above-mentioned limitation also
      affects the accuracy of many biological modifications observed during ECP.
      Starting from these considerations, the need of a prospective randomized study
      becomes increasingly urgent.

PMID- 22587647
TI  - Bacteriocinogenic and virulence potential of Enterococcus isolates obtained from
      raw milk and cheese.
AB  - AIMS: To provide molecular and phenotypical characterization of Enterococcus
      isolates obtained from raw milk and cheese, regarding their bacteriocinogenic and
      virulence activity. METHODS AND RESULTS: Forty-three bacteriocinogenic
      enterococci isolates were identified by 16s rDNA, fingerprinted by RAPD-PCR
      analysis and tested by PCR for the presence of genes for lantibiotics (lanM, lanB
      and lanC) and enterocins (entA, entB, entP, entL50AB and entAS48) and by
      phenotypical methods for bacteriocin production and inhibitory spectrum. Also,
      the virulence of the isolates was evaluated by PCR for genes gelE, hyl, asa1,
      esp, cylA, efaA, ace, vanA, vanB, hdc1, hdc2, tdc and odc and by phenotypical
      tests for gelatinase, lipase, DNAse and alpha- and beta-haemolysis. Most isolates
      (93.0%) harboured at least one lantibiotic or enterocin gene and were positive
      for several tested virulence genes, mainly asa1 (100%), gelE (93.0%) and efaA
      (83.7%). 53.5% of the isolates presented beta-haemolysis [corrected].
      CONCLUSIONS: Enterococcus spp. isolates presented an interesting potential
      application for food preservation because of bacteriocin production; however,
      virulence-related genes were identified in all RAPD profiles. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The study demonstrated the contradictory characteristics of
      the tested Enterococcus isolates: they presented a good potential for application
      in food biopreservation but contained several virulence factors.

PMID- 22587648
TI  - Contraception and antiepileptic drugs.
AB  - Epilepsy is a neurologic condition that affects women and women's choices in many
      areas of their lives. Some antiepileptic drugs (AEDs) used in the treatment of
      epilepsy can interact with hormonal contraceptives. The result can be decreased
      effectiveness in the contraceptive with the possibility of unintended pregnancy,
      or decreased effectiveness of the AED that can result in seizure activity. This
      article provides information about concurrent AED and contraceptive use to assist
      health care providers in guiding women with epilepsy to make the best
      contraceptive choices based on their reproductive life plans.

PMID- 22587649
TI  - Long-term in situ dynamics of the fungal communities in a multi-contaminated soil
      are mainly driven by plants.
AB  - The fungal communities of a multi-contaminated soil polluted by polycyclic
      aromatic hydrocarbons and heavy metals (NM) were studied within a long-term in
      situ experiment of natural attenuation assisted by plants. Three treatments were
      monitored: bare soil (NM-BS), soil planted with alfalfa and inoculated with
      mycorrhizal fungi (NM-Msm), and soil with spontaneous vegetation (NM-SV). The
      same soil after thermal desorption (TD) was planted with alfalfa and inoculated
      with mycorrhizal fungi (TD-Msm). Twice a year for 5 years, the fungal abundance
      and the community structure were evaluated by real-time PCR and temporal
      temperature gradient gel electrophoresis targeting 18S rRNA genes. The fungal
      abundance increased over time and was higher in planted than in bare NM soil and
      in TD than in NM soil. The Shannon diversity index (H') increased during the
      first 2 years with the emergence of more than 30 ribotypes, but decreased after 3
      years with the selection of a few competitive species, mostly Ascomycetes. H' was
      higher under complex plant assemblage (NM-SV) than in the NM-BS plots but did not
      differ between NM and TD soils planted with alfalfa. These results indicated that
      even in a highly polluted soil, the plant cover was the main driver of the fungal
      community structure.

PMID- 22587651
TI  - Multiple H2 occupancy of cages of clathrate hydrate under mild conditions.
AB  - Experiments were carried out by reacting H(2) gas with N(2) hydrate at a
      temperature of 243 K and a pressure of 15 MPa. The characterizations of the
      reaction products indicated that multiple H(2) molecules can be loaded into both
      large and small cages of structure II clathrate hydrates. The realization of
      multiple H(2) occupancy of hydrate cages under moderate conditions not only
      brings new insights into hydrogen clathrates but also refreshes the perspective
      of clathrate hydrates as hydrogen storage media.

PMID- 22587650
TI  - Evaluation of antiproliferative and anti-inflammatory activities of methanol
      extract and its fractions from the Mediterranean sponge.
AB  - BACKGROUND: Without doubt, natural products have been, and still are, the
      cornerstone of the health care armamentarium. Of all natural sources, the marine
      environment is clearly the last great frontier for pharmaceutical and medical
      research. METHODS: This work progresses in the direction of identifying
      component(s) from the Mediterranean sponge, Spongia officinalis with
      pharmacological activities. In the present study we investigated the efficacy of
      methanol extract and its semi-purified fractions (F2, F3) from Spongia
      officinalis for their in vivo anti-inflammatory activity using the carrageenan
      induced paw edema in rats and their in vitro antiproliferative effects by their
      potential cytotoxic activity using the MTT colorimetric method and clonogenic
      inhibition against three human cancer cell lines (A549, lung cell carcinoma,
      HCT15, colon cell carcinoma and MCF7, breast adenocarcinoma). RESULTS: The
      fractions F2 and F3 showed interesting anti-inflammatory and antiproliferative
      activities in a dose dependent manner. CONCLUSIONS: The present study indicates
      that the methanolic extrac and its fractions from Spongia officinalis are a
      significant source of compounds with the antiproliferative and anti-inflammatory
      activities, and this may be useful for developing potential chemopreventive
      substances.

PMID- 22587652
TI  - Uptake and phloem transport of glucose-fipronil conjugate in Ricinus communis
      involve a carrier-mediated mechanism.
AB  - Some compounds containing glucose are absorbed via the monosaccharide
      transporters of the plasma membrane. A glucose-fipronil conjugate, N-[3-cyano-1
      [2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazol
      5-yl]-1-(beta-d-glucopyranosyl)-1H-1,2,3-triazole-4-methanamine (GTF), has been
      synthesized in our previous work. GTF exhibits moderate phloem mobility in
      Ricinus communis. In the current paper, we demonstrate that the uptake of GTF by
      Ricinus seedling cotyledon discs is partly mediated by an active carrier system
      (K(m)1 = 0.17 mM; V(max)1 = 2.2 nmol cm(-2) h(-1)). Four compounds [d-glucose,
      sucrose, phloridzin, and carbonyl cyanide m-chlorophenylhydrazone (CCCP)] were
      examined for their effect on GTF uptake. Phloridzin as well as CCCP markedly
      inhibit GTF uptake, and d-glucose weakly competes with it. The phloem transport
      of GTF in Ricinus seedlings is found to involve an active carrier-mediated
      mechanism that effectively contributes to the GTF phloem loading. The results
      prove that adding a glucose core is a reasonable and feasible approach to confer
      phloem mobility to fipronil by utilizing plant monosaccharide transporters.

PMID- 22587653
TI  - Motor imagery in stroke patients, or plegic patients with spinal cord or
      peripheral diseases.
AB  - OBJECTIVES: When motor imagery (MI) is impaired in stroke patients, it is not
      clear, whether this is caused by the central lesion with a disruption of networks
      or this may be due to inactivity/lack of practice following hemiparesis. To
      answer this question, we investigated MI in two groups of patients: stroke
      patients and patients with no central lesion, who suffered high-grade
      tetraparesis caused by myopathy or spinal muscular atrophy. MATERIALS AND
      METHODS: The first study measured MI in 31 sub-acute and chronic stroke patients
      with hand paresis. We used self-assessment questionnaires [Kinaesthetic and
      Visual Imagery Questionnaire (KVIQ), the Vividness of Motor Imagery Questionnaire
      (VMIQ)] as well as a new chronometric test (mental version and normal/physical
      version of Box and Block Test). The second study assessed MI in 10 patients
      without a central lesion, but with severe tetraparesis of peripheral origin. They
      were incapable of performing the requested task physically. RESULTS: MI in
      patients was better (i) for the third-person (VMIQ(3.P) ) compared to the first
      person perspective (VMIQ(1.P) ), (ii) in patients without sensory impairment
      compared to those with impaired proprioception, (iii) in patients with light
      paresis compared to severe paresis and (iv) for the non-affected than the
      affected hand (KVIQ-10). Patients with severe tetraparesis were able to imagine
      another person's knee bends, but were not capable of imagining themselves
      performing knee bends. CONCLUSIONS: MI may be hampered on the affected side in
      severely paretic patients, particularly in the presence of impaired
      proprioception. Remarkably, the second study illustrates that motor experiences
      shape MI. This confirms the close relationship between MI and movement execution.
      The study advocates the careful use of test batteries for assessment of MI when
      investigating mental training in clinical trials. Not all patients might benefit
      to the same extent from MI training. This is possibly contingent on intact
      proprioception and preserved MI.

PMID- 22587654
TI  - Acoustic and EGG analyses of emotional utterances.
AB  - The aim of the present study was to investigate whether the glottal and filter
      variables of emotional expressions vary by emotion and valence expressed.
      Prolonged emotional vowels (n = 96) were produced by professional actors and
      actresses (n = 4) expressing joy, surprise, interest, sadness, fear, anger,
      disgust, and a neutral emotional state. Acoustic parameters and the contact
      quotient from the electroglottographic signal (CQEGG) were calculated. Statistics
      were calculated for the parameters. Vocal fold contact time differed
      significantly between the emotional expressions reflecting differences in
      phonation types. It was concluded that CQEGG may vary simultaneously and
      inversely with F3 and F4 in emotional expressions of positive emotions. Changes
      in the lower pharynx and larynx may affect the higher formant frequencies.

PMID- 22587655
TI  - Welcome to microbial informatics and experimentation.

PMID- 22587656
TI  - The anniversary issue of Diseases of the Esophagus.

PMID- 22587659
TI  - Long hydrogen-bonded rod of molecular oxide: a hexatantalate tetramer.
AB  - A tetra-n-butylammonium (TBA) salt of [H(4.5)(Ta(6)O(19))](3.5-) was synthesized
      by reacting hydrous tantalum oxide with TBAOH. X-ray structural analysis of
      TBA(3.5)[H(4.5)(Ta(6)O(19))].2THF.5.5H(2)O (THF = tetrahydrofuran) revealed that
      this compound consists of a hydrogen-bonded, rod-shaped tetramer of hexatantalate
      that is almost 30 A long together with TBA cations and solvent molecules of
      crystallization [a = 20.6354(5) A, b = 25.5951(7) A, c = 37.2058(8) A, alpha =
      77.092(1) degrees , beta = 86.177(1) degrees , gamma = 88.683(1) degrees , V =
      19110.9(8) A(3), Z = 8, and space group P 1]. (1)H NMR spectra showed that this
      tetrameric structure is maintained in solution.

PMID- 22587658
TI  - Calcium homeostasis may influence resting energy expenditure with effects most
      apparent in early pubertal girls.
AB  - AIM: Perturbations in dietary and hormonal components of the calciotropic network
      may be mediated through the influence of calcium homoeostasis on resting energy
      expenditure (REE). We investigated the association of dietary and hormonal
      factors involved in the regulation of calcium homoeostasis with REE in girls.
      METHODS: Thirty-six girls aged 7-11 years participated. REE was assessed by
      indirect calorimetry, and body composition, dietary intake (calcium, vitamins D
      and K, phosphorus) and serum hormones (PTH, osteocalcin, 25OHD) were evaluated by
      DXA, 24 h recall and serum assay, respectively. RESULTS:   A positive association
      between vitamin K and REE and an inverse association of parathyroid hormone (PTH)
      with REE (p = 0.05) were observed. PTH and REE were positively related in those
      having normal adiposity (p = 0.03) and inversely related in those with excess
      adiposity (p = 0.01). The association of REE with vitamin K intake was evident in
      lean individuals (p = 0.001), but was null in those with excess adiposity.
      CONCLUSION: Decreased calciotropic hormone levels along with increased related
      nutrient intakes were associated with greater REE, although these relationships
      differed according to adiposity. The physiologic response to the diet and
      subsequent energy partitioning needs to be considered in the context of puberty.
      In particular, regulation and signalling of the calciotropic network during
      pubertal maturation warrant investigation.

PMID- 22587660
TI  - A case of ovarian hyperstimulation syndrome following a spontaneous complete
      hydatidiform molar pregnancy.
AB  - INTRODUCTION: To present a rare case of ovarian hyperstimulation syndrome (OHSS)
      following a spontaneous complete hydatidiform molar (CHM) pregnancy. CASE: A 38
      year-old woman underwent vacuum curettage for a CHM pregnancy. Seven days later,
      she was admitted to our hospital with the symptoms of OHSS. Transvaginal
      ultrasonography demonstrated enlarged multicystic ovaries, marked ascites and
      large pleural effusions that required abdominocentesis and thoracocentesis,
      respectively. She was treated with intravenous fluid, exogenous colloid
      supplementation, prophylaxis for deep vein thrombosis, and drainage of the
      ascites and bilateral pleural effusions. She recovered by day 14 of admission.
      CONCLUSION: OHSS may develop in older women who undergo treatment for CHM
      pregnancies. Serious complications may develop rapidly and therefore the prompt
      diagnosis of OHSS is very important.

PMID- 22587662
TI  - Catheter ablation of cavotricuspid isthmus dependent atrial flutter: manual
      skills or technology or both?

PMID- 22587661
TI  - Hypoglycaemia related to inherited metabolic diseases in adults.
AB  - In non-diabetic adult patients, hypoglycaemia may be related to drugs, critical
      illness, cortisol or glucagon insufficiency, non-islet cell tumour, insulinoma,
      or it may be surreptitious. Nevertheless, some hypoglycaemic episodes remain
      unexplained, and inborn errors of metabolism (IEM) should be considered,
      particularly in cases of multisystemic involvement. In children, IEM are
      considered a differential diagnosis in cases of hypoglycaemia. In adulthood, IEM
      related hypoglycaemia can persist in a previously diagnosed childhood disease.
      Hypoglycaemia may sometimes be a presenting sign of the IEM. Short stature,
      hepatomegaly, hypogonadism, dysmorphia or muscular symptoms are signs suggestive
      of IEM-related hypoglycaemia. In both adults and children, hypoglycaemia can be
      clinically classified according to its timing. Postprandial hypoglycaemia can be
      an indicator of either endogenous hyperinsulinism linked to non-insulinoma
      pancreatogenic hypoglycaemia syndrome (NIPHS, unknown incidence in adults) or
      very rarely, inherited fructose intolerance. Glucokinase-activating mutations
      (one family) are the only genetic disorder responsible for NIPH in adults that
      has been clearly identified so far. Exercise-induced hyperinsulinism is linked to
      an activating mutation of the monocarboxylate transporter 1 (one family). Fasting
      hypoglycaemia may be caused by IEM that were already diagnosed in childhood and
      persist into adulthood: glycogen storage disease (GSD) type I, III, 0, VI and IX;
      glucose transporter 2 deficiency; fatty acid oxidation; ketogenesis disorders;
      and gluconeogenesis disorders. Fasting hypoglycaemia in adulthood can also be a
      rare presenting sign of an IEM, especially in GSD type III, fatty acid oxidation
      [medium-chain acyl-CoA dehydrogenase (MCAD), ketogenesis disorders (3-hydroxy-3
      methyl-glutaryl-CoA (HMG-CoA) lyase deficiency, and gluconeogenesis disorders
      (fructose-1,6-biphosphatase deficiency)].

PMID- 22587663
TI  - Glucocorticoid receptor-promoter interactions: energetic dissection suggests a
      framework for the specificity of steroid receptor-mediated gene regulation.
AB  - The glucocorticoid receptor (GR) is a member of the steroid receptor family of
      ligand-activated transcription factors. A number of studies have shown that
      steroid receptors regulate distinct but overlapping sets of genes; however, the
      molecular basis for such specificity remains unclear. Previous work from our
      laboratory has demonstrated that under identical solution conditions, three other
      steroid receptors [the progesterone receptor A isoform (PR-A), the progesterone
      receptor B isoform (PR-B), and estrogen receptor alpha (ER-alpha)] differentially
      partition their self-association and promoter binding energetics. For example, PR
      A and PR-B generate similar dimerization free energies but differ significantly
      in their extents of intersite cooperativity. Conversely, ER-alpha maintains an
      intersite cooperativity most comparable to that of PR-A yet dimerizes with an
      affinity orders of magnitude greater than that of either of the PR isoforms. We
      have speculated that these differences serve to generate receptor-specific
      promoter occupancies, and thus receptor-specific gene regulation. Noting that GR
      regulates a unique subset of genes relative to the other receptors, we
      hypothesized that the receptor should maintain a unique set of interaction
      energetics. We rigorously determined the self-association and promoter binding
      energetics of full-length, human GR under conditions identical to those used in
      our earlier studies. We find that unlike all other receptors, GR shows no
      evidence of reversible self-association. Moreover, GR assembles with strong
      intersite cooperativity comparable to that seen only for PR-B. Finally,
      simulations show that such partitioning of interaction energetics allows for
      receptor-specific promoter occupancies, even under conditions where multiple
      receptors are competing for binding at identical sites.

PMID- 22587665
TI  - Models of the radiation-induced bystander effect.
AB  - PURPOSE: To implement quantitative models of the Radiation-Induced Bystander
      Effects (RIBE) based on cellular excitation at a rate proportional to the
      concentration of signal molecules (called signals here) released by irradiated
      cells. Clonogenic cell survival and transformation frequency as a function of
      rescue time and dose were considered. MATERIALS AND METHODS: Our first stochastic
      model was based on the hypothesis that chemical signals are released into the
      extracellular medium by irradiated cells. These signals act on unirradiated cells
      switching them from the healthy to the dead state at rate R(t). We extended this
      model including a non-lethal transformed state in order to describe clonogenic
      cell survival and transformation frequency as a function of the number of alpha
      particles. RESULTS: The first stochastic model was applied to an experiment on
      human keratinocyte (HaCat) cells yielding the half-life of at least one signal
      among the ensemble of possible candidates to trigger cell death in this cell
      culture. The second model yielded good fits to the data on clonogenic cell
      survival and transformation frequency in microbeam experiments with mouse embryo
      (C3H10T(1/2)) cells (Sawant et al. 2001a, 2001b). CONCLUSIONS: The fit of the
      first stochastic model to HaCat cell survival yielded a half-life of the order of
      minutes for possible signal candidates. This model also furnished the variance of
      the fraction of surviving cells.

PMID- 22587666
TI  - 'Boots for my Sancho': structural vulnerability among Latin American day
      labourers in Berkeley, California.
AB  - This paper addresses the structural vulnerability of Latin American undocumented
      day labourers in Northern California, as it is expressed in conversations on
      street corners where they wait for work. The intimate aspects of migrant
      experience become exemplified in jokes about the Sancho - a hypothetical
      character who has moved in on a day labourer's family and who enjoys the money he
      sends home. Joking turns to more serious topics of nostalgia and tensions with
      family far away, elements that come together with the fears and threats of labour
      on the corner and affect the way day labourers see themselves. Sexuality is
      rearticulated in the absence of women and masculinity becomes enmeshed in the
      contingencies of unregulated work and long-term separation from the people the
      men support. Together, these elements result in the articulation of threat to the
      immigrant body itself, which is exemplified by anxieties over homosexual
      propositions on the corner.

PMID- 22587664
TI  - Hydrogen-rich saline alleviates early brain injury via reducing oxidative stress
      and brain edema following experimental subarachnoid hemorrhage in rabbits.
AB  - BACKGROUND: Increasing experimental and clinical data indicate that early brain
      injury (EBI) after subarachnoid hemorrhage (SAH) largely contributes to
      unfavorable outcomes, and it has been proved that EBI following SAH is closely
      associated with oxidative stress and brain edema. The present study aimed to
      examine the effect of hydrogen, a mild and selective cytotoxic oxygen radical
      scavenger, on oxidative stress injury, brain edema and neurology outcome
      following experimental SAH in rabbits. RESULTS: The level of MDA, caspase-12/3
      and brain water content increased significantly at 72 hours after experimental
      SAH. Correspondingly, obvious brain injury was found in the SAH group by terminal
      deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end
      labeling (TUNEL) and Nissl staining. Similar results were found in the SAH+saline
      group. In contrast, the upregulated level of MDA, caspase-12/3 and brain edema
      was attenuated and the brain injury was substantially alleviated in the hydrogen
      treated rabbits, but the improvement of neurology outcome was not obvious.
      CONCLUSION: The results suggest that treatment with hydrogen in experimental SAH
      rabbits could alleviate brain injury via decreasing the oxidative stress injury
      and brain edema. Hence, we conclude that hydrogen possesses the potential to be a
      novel therapeutic agent for EBI after SAH.

PMID- 22587667
TI  - Adsorption of chain type-specific ABO antibodies on Sepharose-linked A and B
      tetrasaccharides.
AB  - BACKGROUND: Antigen-specific removal of anti-A and anti-B on immunoadsorption
      columns carrying the blood group A and B trisaccharides is one important
      component of some protocols used in ABO-incompatible organ transplantation.
      Because ABO antibodies exist requiring parts of the core saccharide chain for
      binding, the anti-A and -B-binding capacity of individual and combined, Sepharose
      linked Types 1 through 4 A and B tetrasaccharides with that of the A and B
      trisaccharides was compared. STUDY DESIGN AND METHODS: Sepharose-linked A and B
      tri- and tetrasaccharides were used to adsorb anti-A and -B from pooled blood
      group O serum. Remaining chain type-specific anti-A and -B were detected and
      quantified in enzyme-linked immunosorbent assays using wells coated with
      neoglycoproteins or recombinant mucins carrying A and B determinants on defined
      core saccharide chains. RESULTS: Significantly more anti-A Type 3- and 4-specific
      immunoglobulin (Ig)G remained after adsorption on the A trisaccharide and the A
      Type 1 and A Type 2 tetrasaccharide than after adsorption on the A Types 3 and 4
      tetrasaccharides. Selective adsorption of chain type-specific IgG anti-B was
      detected on Sepharose-linked B tetrasaccharides. In contrast, there were no chain
      type-specific IgM anti-A or -B. A combination of the A or B tetrasaccharides
      adsorbed a larger fraction of the IgG anti-A and -B repertoires than the
      corresponding trisaccharides. CONCLUSION: There are chain type-specific anti-A
      and anti-B IgG, and an adsorber based on a combination of Types 1 through 4 A or
      B tetrasaccharides will be a more efficient adsorber than an adsorber based on
      the A or B trisaccharides.

PMID- 22587668
TI  - Variability and concordance of Cornell and Sokolow-Lyon electrocardiographic
      criteria in hypertensive patients.
AB  - AIM: To assess the variability and concordance of left ventricular hypertrophy
      electrocardiographic (LVH-ECG) criteria. METHODS AND RESULTS: Convenience
      sampling of hypertensive subjects without coronary disease or bundle branch
      blocks. Two electrocardiograms (ECGs) were performed on each patient. Two
      investigators carried out two blind-readings of each ECG (Cornell and Sokolow
      Lyon criteria). The between-rater and within-rater reliability were assessed
      (intraclass correlation coefficient, ICC). Poor concordance was defined: mean
      voltage difference between both ECGs >2 mm; 824 ECG readings were performed in
      103 subjects (58.3% females), aged 66.8+/-8.8 years, mean blood pressure 141+/
      15.10/78+/-9.0 mmHg. The between-rater ICCs of the baseline ECG were 0.97(95% CI
      0.96-0.98) and 0.98 (95% CI 0.97-0.99) for Cornell and Sokolow-Lyon criteria,
      respectively. Poor concordance was found in 39.8% and in 41.7% of the cases for
      Cornell and Sokolow-Lyon criteria, respectively. Systolic blood pressure was
      found to be significant and positively associated with both criteria. Elderly
      hypertensive subjects, with higher ECG voltages and lower pulse pressure
      presented poor concordance of Cornell criteria. CONCLUSIONS: The between-rater
      and within-rater reliability of Cornell and Sokolow-Lyon criteria is minimal.
      Approximately 40% of hypertensive subjects presented poor concordance in a second
      ECG. Older patients with lower pulse pressure and higher baseline voltages
      presented poorer reproducibility of LVH-ECG criteria.

PMID- 22587670
TI  - Application of microflow conditions to visible light photoredox catalysis.
AB  - Applications of microflow conditions for visible light photoredox catalysis have
      successfully been developed. Operationally simple microreactor and FEP
      (fluorinated ethylene propylene copolymer) tube reactor systems enable
      significant improvement of several photoredox reactions using different
      photocatalysts such as [Ru(bpy)(3)](2+) and Eosin Y. Apart from rate
      acceleration, this approach facilitates previously challenging transformations of
      nonstabilized intermediates. Additionally, the productivity of the synergistic,
      catalytic enantioselective photoredox alpha-alkylation of aldehydes was
      demonstrated to be increased by 2 orders of magnitude.

PMID- 22587669
TI  - Fabrication and characterization of WO3/Ag/WO3 multilayer transparent anode with
      solution-processed WO3 for polymer light-emitting diodes.
AB  - The dielectric/metal/dielectric multilayer is suitable for a transparent
      electrode because of its high-optical and high-electrical properties; however, it
      is fabricated by an expensive and inefficient multistep vacuum process. We
      present a WO3/Ag/WO3 (WAW) multilayer transparent anode with solution-processed
      WO3 for polymer light-emitting diodes (PLEDs). This WAW multilayer not only has
      high transmittance and low resistance but also can be easily and rapidly
      fabricated. We devised a novel method to deposit a thin WO3 layer by a solution
      process in an air environment. A tungstic acid solution was prepared from an
      aqueous solution of Na2WO4 and then converted to WO3 nanoparticles (NPs) by a
      thermal treatment. Thin WO3 NP layers form WAW multilayer with a thermal
      evaporated Ag layer, and they improve the transmittance of the WAW multilayer
      because of its high transmittance and refractive index. Moreover, the surface of
      the WO3 layer is homogeneous and flat with low roughness because of the WO3 NP
      generation from the tungstic acid solution without aggregation. We performed
      optical simulation and experiments, and the optimized WAW multilayer had a high
      transmittance of 85% with a sheet resistance of 4 Omega/sq. Finally, PLEDs based
      on the WAW multilayer anode achieved a maximum luminance of 35,550 cd/m2 at 8 V,
      and this result implies that the solution-processed WAW multilayer is appropriate
      for use as a transparent anode in PLEDs.

PMID- 22587671
TI  - Candidate biomarkers for acute rejection of pregnancy after in-utero cell-based
      therapy in pre-immune embryos via ultrasound-guided celocentesis.
AB  - PROBLEM: A maternal serum biomarker profile analysis was performed to determine
      potential indicators of acute rejection of pregnancy following in-utero cell
      based treatments in pre-immune embryos. METHOD OF STUDY: We used an established
      non-human primate model for in-utero stem cell therapy at 38-42 days from
      fertilization. The maternal serum concentrations of nine candidate biomarkers for
      acute rejection of pregnancy were determined before and after the injection of
      different cocktails of human umbilical cord blood stem cells into the gestational
      sac. All animals were then followed until delivery. RESULTS: Twenty-four hours
      after celocentesis, two of the animals aborted. These two animals received a
      cocktail of haemopoietic stem cells with the highest concentration of human
      CD3(+)  cells and showed a twofold increase in maternal serum IL-6 and a
      threefold increase in prolactin after the procedure. The remaining six animals
      delivered at term live and normal newborns and only demonstrated an increase in
      prolactin after the celocentesis procedure. CONCLUSION: IL-6 and prolactin are
      master immunoregulators with pleiotropic biological functions that have different
      maternal serum concentrations depending on pregnancy outcome. These findings
      suggest that increases in maternal serum prolactin and IL-6 concentration may be
      associated with acute rejection of pregnancy after in-utero stem cell therapy.

PMID- 22587672
TI  - Translational web robots for pathogen genome analysis.

PMID- 22587673
TI  - Do colonization by dark septate endophytes and elevated temperature affect
      pathogenicity of oomycetes?
AB  - Phialocephala subalpina is one of the most frequent dark septate root endophytes
      in tree roots but its function in forest ecosystems is largely unknown. A full
      factorial infection experiment was performed, using six P. subalpina isolates,
      two pathogenic oomycetes (Phytophthora plurivora [syn. Phytophthora citricola
      s.l.] and Elongisporangium undulatum [syn. Pythium undulatum]) and two
      temperature regimes (17.9 and 21.6  degrees C) to examine the ability of P.
      subalpina to protect Norway spruce seedlings against root pathogens. Seedling
      survival, disease intensity and seedling growth were affected by P. subalpina
      genotype, temperature and pathogen species. Some P. subalpina isolates
      effectively reduced mortality and disease intensity caused by the two pathogens.
      Elevated temperature adversely affected seedling growth but did not aggravate the
      effect of the pathogens. Elongisporangium undulatum but not P. plurivora
      significantly reduced plant growth. Colonization density of P. subalpina measured
      by quantitative PCR was not affected by temperature or the presence of the
      pathogens. In conclusion, P. subalpina confers an indirect benefit to its host
      and might therefore be tolerated in natural ecosystems, despite negative effects
      on plant health and plant growth.

PMID- 22587675
TI  - Systematic review shows certified nurse-midwives are safe and effective.

PMID- 22587676
TI  - Solid-state water electrolysis with an alkaline membrane.
AB  - We report high-performance, durable alkaline membrane water electrolysis in a
      solid-state cell. An anion exchange membrane (AEM) and catalyst layer ionomer for
      hydroxide ion conduction were used without the addition of liquid electrolyte. At
      50  degrees C, an AEM electrolysis cell using iridium oxide as the anode catalyst
      and Pt black as the cathode catalyst exhibited a current density of 399 mA/cm(2)
      at 1.80 V. We found that the durability of the AEM-based electrolysis cell could
      be improved by incorporating a highly durable ionomer in the catalyst layer and
      optimizing the water feed configuration. We demonstrated an AEM-based
      electrolysis cell with a lifetime of >535 h. These first-time results of water
      electrolysis in a solid-state membrane cell are promising for low-cost, scalable
      hydrogen production.

PMID- 22587674
TI  - Incidence and risk for traumatic and overuse injuries in top-level road cyclists.
AB  - All traumatic and overuse injuries occurring during an average period of 4 years
      (2002/09) in a group of 51 currently active road top-level cyclists were
      retrospectively registered through clinical interviews. Average age was 25.8
      years. Average training and competition period was 28.3 +/- 2.4 h a week. Only 8
      cyclists (15.6%) were completely free from lesions during the period of study.
      The remaining 43 cyclists suffered a total of 112 lesions; however, 9 out of
      these were unrelated to their cycling practice. These 103 cycling-related
      injuries include 50 (48.5%) traumatic and 53 (51.5%) overuse injuries. Twenty
      eight fractures were reported, the clavicle being the most frequently affected
      bone (11 cases). The 68.5% of overuse injuries were located in the lower limbs.
      Most overuse injuries (89.6%) occurred during the training period. According to
      the injury abbreviated scale (AIS), severe lesions were only found in 4 cases (8%
      of traumatic injuries). Overall injury rates were 0.50 per racer/year, 2.02 per
      studied racer, and 0.007 per 1000 km of training and competition. Active
      professional top-level cyclists are exposed to a high injury risk. According to
      the scarce previously published data the current study provides relevant
      information on the injury occurrence of still active top-level road cycling.

PMID- 22587677
TI  - The expression of suppressor of cytokine signaling 1 and 3 in fat and placental
      tissue from women with gestational diabetes.
AB  - The suppressor of cytokine signaling (SOCS) proteins are feedback inhibitors of
      signaling pathways induced by cytokines, hormones and growth factors. In the
      present study we measured the expression of SOCS1, SOCS3, interleukin-6 (IL-6),
      IL-6 receptor, IL-8 and leptin mRNA in paired samples of subcutaneous adipose
      tissue (SAT), visceral adipose tissue (VAT) and placental tissue obtained from 18
      pregnant women with normal glucose tolerance (NGT) and 20 subjects with
      gestational diabetes mellitus (GDM), using quantitative RT-PCR. The patients with
      GDM had significantly higher IL-8 mRNA expression in VAT than the women with NGT
      (p = 0.007), whereas the expression of SOCS1, SOCS3 and other genes study did not
      differ significantly between the two groups. Stepwise regression analysis
      revealed that SOCS1 mRNA expression in VAT was significantly associated with
      prepregnancy BMI (beta = -0.68, p = 0.03) and IL-8 mRNA expression (beta = 0.66,
      p = 0.03), whereas SOCS3 mRNA expression in VAT was independently predicted by IL
      6 mRNA expression (beta = 0.94, p = 0.0002, R(2) = 0.88). In conclusion, our
      results did not show significant differences in SOCS1 and SOCS3 mRNA expression
      in adipose and placental tissue obtained from pregnant women with and without
      GDM.

PMID- 22587678
TI  - Design of a dinuclear nickel(II) bioinspired hydrolase to bind covalently to
      silica surfaces: synthesis, magnetism, and reactivity studies.
AB  - Presented herein is the design of a dinuclear Ni(II) synthetic hydrolase
      [Ni(2)(HBPPAMFF)(MU-OAc)(2)(H(2)O)]BPh(4) (1) (H(2)BPPAMFF = 2-[(N-benzyl-N-2
      pyridylmethylamine)]-4-methyl-6-[N-(2-pyridylmethyl)aminomethyl)])-4-methyl-6
      formylphenol) to be covalently attached to silica surfaces, while maintaining its
      catalytic activity. An aldehyde-containing ligand (H(2)BPPAMFF) provides a
      reactive functional group that can serve as a cross-linking group to bind the
      complex to an organoalkoxysilane and later to the silica surfaces or directly to
      amino-modified surfaces. The dinuclear Ni(II) complex covalently attached to the
      silica surfaces was fully characterized by different techniques. The catalytic
      turnover number (k(cat)) of the immobilized Ni(II)Ni(II) catalyst in the
      hydrolysis of 2,4-bis(dinitrophenyl)phosphate is comparable to the homogeneous
      reaction; however, the catalyst interaction with the support enhanced the
      substrate to complex association constant, and consequently, the catalytic
      efficiency (E = k(cat)/K(M)) and the supported catalyst can be reused for
      subsequent diester hydrolysis reactions.

PMID- 22587679
TI  - Iron oxide/hydroxide nanoparticles with negatively charged shells show increased
      uptake in Caco-2 cells.
AB  - The absorption of commonly used ferrous iron salts from intestinal segments at
      neutral to slightly alkaline pH is low, mainly because soluble ferrous iron is
      easily oxidized to poorly soluble ferric iron and because ferrous iron, but not
      ferric iron, is carried by the divalent metal transporter DMT-1. Moreover,
      ferrous iron frequently causes gastrointestinal side effects. Iron hydroxide
      nanoparticles with neutral and hydrophilic carbohydrate shells are alternatively
      used to ferrous salts. In these formulations gastrointestinal side effects are
      rare because hundreds of ferric iron atoms are safely packed in nanoscaled cores
      surrounded by the solubilizing shell; nevertheless, iron bioavailability is even
      worse compared to ferrous salts. In this study the cell uptake of iron hydroxide
      and iron oxide nanoparticles (FeONP) with negatively charged shells of different
      chemical types and sizes was compared to the uptake of those with neutral
      hydrophilic shells, ferrous sulfate and ferric chloride. The nanoparticle uptake
      was measured in Caco-2 cells with the iron detecting ferrozine method and
      visualized by transmission electron microscopy. The toxicity was evaluated using
      the MTT assay. For nanoparticles with a negatively charged shell the iron uptake
      was about 40 times higher compared to those with neutral hydrophilic carbohydrate
      shell or ferric chloride and in the same range as ferrous sulfate. However, in
      contrast to ferrous sulfate, nanoparticles with negatively charged shells showed
      no toxicity. Two different uptake mechanisms were proposed: diffusion for
      hydroxide nanoparticles with neutral hydrophilic shell and adsorptive endocytosis
      for nanoparticles with negatively charged shells. It needs to be determined
      whether iron hydroxide nanoparticles with negatively charged shells also show
      improved bioavailability in iron-deficient patients compared to iron hydroxide
      nanoparticles with a neutral hydrophilic shell, which exist in the market today.

PMID- 22587680
TI  - While we are waiting for NFOG 2012 and summer, enjoy this issue of AOGS.

PMID- 22587682
TI  - A mutation in KIF7 is responsible for the autosomal recessive syndrome of
      macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance.
AB  - BACKGROUND: We previously reported the existence of a unique autosomal recessive
      syndrome consisting of macrocephaly, multiple epiphyseal dysplasia and
      distinctive facial appearance mapping to chromosome 15q26. METHODS: In this
      manuscript, we have used whole exome sequencing on two affected members of a
      consanguineous family with this condition and carried out detailed bioinformatics
      analysis to elucidate the causative mutation. RESULTS: Our analysis resulted in
      the identification of a homozygous p.N1060S missense mutation in a highly
      conserved residue in KIF7, a regulator of Hedgehog signaling that has been
      recently found to be causing Joubert syndrome, fetal hydrolethalus and
      acrocallosal syndromes. The phenotype in our patients partially overlaps with the
      phenotypes associated with those syndromes but they also exhibit some distinctive
      features including multiple epiphyseal dysplasia. CONCLUSIONS: We report the
      first missense homozygous disease-causing mutation in KIF7 and expand the
      clinical spectrum associated with mutations in this gene to include multiple
      epiphyseal dysplasia. The missense nature of the mutation might account for the
      unique presentation in our patients.

PMID- 22587683
TI  - Leishmania (V.) braziliensis and L. (L.) amazonensis promote differential
      expression of dendritic cells and cellular immune response in murine model.
AB  - The expression of Langerhans cell (LC) and dermal dendritic cell (dDC) as well as
      T CD4(+) and CD8(+) immune responses was evaluated in the skin of BALB/c mice
      experimentally infected by L. (L.) amazonensis (La) and L. (V.) braziliensis
      (Lb). At 4th and 8th weeks post infection (PI), skin biopsies were collected to
      determine the parasite load and CD207(+), CD11c(+), CD4(+), CD8(+), iNOS(+)
      cellular densities. Cytokine (IFN-gamma, IL-4 and IL-10) profiles were also
      analysed in draining lymph node. At 4th week, the densities of CD207(+) and
      CD11c(+) were higher in the La infection, while in the Lb infection, these
      markers revealed a significant increase at 8th week. At 4th week, CD4(+) and
      CD8(+) were higher in the La infection, but at 8th week, there was a substantial
      increase in both markers in the Lb infection. iNOS(+) was higher in the Lb
      infection at 4th and 8th weeks. In contrast, the parasite load was higher in the
      La infection at 4th and 8th weeks. The concentration of IFN-gamma was higher in
      the Lb infection, but IL-4 and IL-10 were higher in the La infection at 4th and
      8th weeks. These results confirm the role of the Leishmania species in the BALB/c
      mice disease characterized by differences in the expression of dendritic cells
      and cellular immune response.

PMID- 22587685
TI  - Incidence and clinical characteristics of myeloproliferative neoplasms displaying
      a PDGFRB rearrangement.
AB  - OBJECTIVES: The myeloproliferative neoplasms displaying a PDGFRB rearrangement
      are rare diseases derived from a haematopoietic stem cell. The goals of the study
      were to assess the incidence of these disorders and to define the clinical and
      biological characteristics as well as the response to the imatinib therapy.
      METHODS: A total of 556 patients with myeloproliferative neoplasms were studied
      by means of molecular cytogenetics. RESULTS: The incidence of myeloproliferative
      neoplasms (MPN) with PDGFRB rearrangement was low (10 cases, 1.8% of all MPN).
      Most of the patients showed moderate anaemia (median Hb was 10.0 gr/dL; range
      from 7.5 to 13 g/dL), leukocytosis (median white blood cells was 21.7 * 10(9) /L
      with a range from 4 to 43 * 10(9) /L) and eosinophilia (median circulating
      eosinophils was 2.4 * 10(9) /L with a range of 1.1-5.7 * 10(9) /L) with a median
      of bone marrow infiltration cells displaying PDGFRB rearrangement of 55% (range,
      37-85%). In three cases, a t(5;12) was observed while two patients showed
      rearrangements of 17q21 region. In two cases, a del(5)(q31) was observed. Most of
      the patients responded to standard dosage of imatinib, and the response was
      maintained in the time in those patients with a follow-up higher than 9 years.
      CONCLUSIONS: The incidence of patients with PDGFRB rearrangement is low. These
      patients showed leukocytosis with eosinophilia and anaemia. The efficacy of
      imatinib therapy in patients showing PDGFRB rearrangement is high. For this
      reason, in all patients with MPN without any other molecular aberration, PDGFRB
      rearrangement should be ascertained.

PMID- 22587684
TI  - Effectiveness of two intensive treatment methods for smoking cessation and
      relapse prevention in patients with coronary heart disease: study protocol and
      baseline description.
AB  - BACKGROUND: There is no more effective intervention for secondary prevention of
      coronary heart disease than smoking cessation. Yet, evidence about the (cost
      )effectiveness of smoking cessation treatment methods for cardiac inpatients that
      also suit nursing practice is scarce. This protocol describes the design of a
      study on the (cost-)effectiveness of two intensive smoking cessation
      interventions for hospitalised cardiac patients as well as first results on the
      inclusion rates and the characteristics of the study population. METHODS/DESIGN:
      An experimental study design is used in eight cardiac wards of hospitals
      throughout the Netherlands to assess the (cost-)effectiveness of two intensive
      smoking cessation counselling methods both combined with nicotine replacement
      therapy. Randomization is conducted at the ward level (cross-over). Baseline and
      follow-up measurements after six and 12 months are obtained. Upon admission to
      the cardiac ward, nurses assess patients' smoking behaviour, ensure a quit advice
      and subsequently refer patients for either telephone counselling or face-to-face
      counselling. The counselling interventions have a comparable structure and
      content but differ in provider and delivery method, and in duration. Both
      counselling interventions are compared with a control group receiving no
      additional treatment beyond the usual care. Between December 2009 and June 2011,
      245 cardiac patients who smoked prior to hospitalisation were included in the
      usual care group, 223 in the telephone counselling group and 157 in the face-to
      face counselling group. Patients are predominantly male and have a mean age of 57
      years. Acute coronary syndrome is the most frequently reported admission
      diagnosis. The ultimate goal of the study is to assess the effects of the
      interventions on smoking abstinence and their cost-effectiveness. Telephone
      counselling is expected to be more (cost-)effective in highly motivated patients
      and patients with high SES, whereas face-to-face counselling is expected to be
      more (cost-)effective in less motivated patients and patients with low SES.
      DISCUSSION: This study examines two intensive smoking cessation interventions for
      cardiac patients using a multi-centre trial with eight cardiac wards. Although
      not all eligible patients could be included and the distribution of patients is
      skewed in the different groups, the results will be able to provide valuable
      insight into effects and costs of counselling interventions varying in delivery
      mode and intensity, also concerning subgroups. TRIAL REGISTRATION: Dutch Trial
      Register NTR2144.

PMID- 22587686
TI  - Pharmacokinetic evaluation of  atorvastatin and sitagliptin  in combination for
      the treatment of type 2 diabetes.
AB  - INTRODUCTION: Patients with type 2 diabetes (T2DM) are exposed to a high risk of
      cardiovascular disease (CVD) requiring a global therapeutic approach. Statin
      therapy has proven its efficacy in reducing CVD events in T2DM patients.
      Dipeptidylpeptidase-4 inhibitors (gliptins), which are increasingly used to
      target hyperglycemia, also offer promising preliminary results regarding a
      possible reduction in CVD events. As most patients with T2DM may be treated with
      both a statin and a gliptin, dual pharmacological therapy, possibly as a fixed
      dose combination (FDC), deserves further consideration. AREAS COVERED: The reader
      is provided with an update of information on the pharmacokinetics (PK) and
      pharmacodynamics (PD) of atorvastatin and sitagliptin . The article provides an
      analysis of the potential PK/PD interactions between the two compounds and puts
      into perspective the potential cardiovascular protection that such a dual therapy
      may offer in patients with T2DM. EXPERT OPINION: Atorvastatin and sitagliptin are
      not prone to PK drug-drug interactions. Their coadministration, either separately
      or in an FDC, improves both blood glucose levels and cholesterol concentrations,
      without clinically relevant adverse events. The atorvastatin plus sitagliptin
      combination may be used to reduce LDL cholesterol and hyperglycemia in patients
      with T2DM, with the aim to improve CVD prognosis and adherence to therapy.

PMID- 22587687
TI  - Efficacy of ICON(r) Maxx in the laboratory and against insecticide-resistant
      Anopheles gambiae in central Cote d'Ivoire.
AB  - BACKGROUND: Long-lasting treatment kits, designed to transform untreated nets
      into long-lasting insecticidal nets (LLINs), may facilitate high coverage with
      LLINs where non-treated nets are in place. In this study, the efficacy of ICON(r)
      Maxx (Syngenta) was evaluated under laboratory conditions and in an experimental
      hut trial in central Cote d'Ivoire, where Anopheles gambiae s.s. are resistant to
      pyrethroid insecticides. METHODS: In the laboratory, polyester and polyethylene
      net samples were treated with ICON(r) Maxx, washed up to 20 times and their
      efficacy determined in World Health Organization (WHO) cone assays against a
      susceptible laboratory An. gambiae s.s. colony. Over a 12-month period, the
      polyester nets were evaluated in a hut trial to determine mosquito deterrence,
      induced exophily, blood-feeding inhibition and mortality. RESULTS: In the
      laboratory, ICON(r) Maxx-treated polyethylene nets showed higher efficacy against
      pyrethroid-susceptible mosquitoes than polyester nets. After 20 washings,
      insecticidal efficacy in bioassays was 59.4% knockdown (KD) and 22.3% mortality
      for polyethylene, and 55.3% KD and 17.9% mortality for polyester nets. In
      experimental huts, treated nets showed strong deterrence, induced exophily and an
      over three-fold reduction in blood-fed mosquitoes. More than half (61.8%) of the
      mosquitoes entering the huts with treated nets were found dead the next morning
      despite high levels of KD resistance. After washing the treated nets, KD and
      mortality rates were close to or exceeded predefined WHO thresholds in cone
      bioassays. CONCLUSION: In contrast to previous laboratory investigation, ICON(r)
      Maxx-treated nets showed only moderate KD and mortality rates. However, under
      semi-field conditions, in an area where mosquitoes are resistant to pyrethroids,
      ICON(r) Maxx showed high deterrence, induced exophily and provided a significant
      reduction in blood-feeding rates; features that are likely to have a positive
      impact in reducing malaria transmission. The WHO cone test may not always be a
      good proxy for predicting product performance under field conditions.

PMID- 22587689
TI  - Ageing, sexuality and enhancement among Yoruba people in south western Nigeria.
AB  - Sexual health across the life course is influenced by biological and psychosocial
      factors. The paper explores sexuality and associated practices among older Yoruba
      people with a view to identifying the implications of cultural beliefs and
      practices for sexual health in later life. A total of 64 vignette-based in-depth
      interviews and 12 focus-group discussions were held with older adults (50-75
      years) in two Yoruba communities in south western Nigeria. Findings portray
      sexuality as an important aspect of old age, with sexual intercourse being
      construed as having physical and spiritual consequences. This same perspective
      also emerged as participants' attributed factors affecting sexual desire in old
      age to religious beliefs, poverty, ill health and the non-availability of a
      partner. Gender differences were dominant on sexual desire and pleasure in old
      age. Participants' views on causes of sexual dysfunction identified biological,
      psychosocial and spiritual factors. Sexual decline in old age was considered
      redeemable with the support of biomedical and traditional medicines. However,
      only traditional medicine was considered beneficial in addressing sexual
      dysfunctions that had spiritual dimensions.

PMID- 22587688
TI  - NXL104 irreversibly inhibits the beta-lactamase from Mycobacterium tuberculosis.
AB  - NXL104 is a novel beta-lactamase inhibitor with a non-lactam structural scaffold.
      Our kinetic and mass spectrometric analysis demonstrates that NXL104
      quantitatively inhibits BlaC, the only chromosomally encoded beta-lactamase from
      Mycobacterium tuberculosis, by forming a carbamyl adduct with the enzyme. The
      inhibition efficiency (k(2)/K) of NXL104 was shown to be more than 100-fold lower
      than that of clavulanate, a classical beta-lactamase inhibitor, which is probably
      caused by the bulky rings of NXL104. However, the decarbamylation rate constant
      (k(3)) was determined to be close to zero. The BlaC-NXL104 adduct remained stable
      for at least 48 h, while the hydrolysis of the BlaC-clavulanate adduct was
      observed after 2 days. The three-dimensional crystal structure of the BlaC-
      NXL104 carbamyl adduct was determined at a resolution of 2.3 A. Interestingly,
      the sulfate group of NXL104 occupies the position of a phosphate ion in the
      structure of the BlaC-clavulanate adduct and is hydrogen bonded to residues
      Ser128, Thr237, and Thr239. Favorable interactions are also seen in the
      electrostatic potential map. We propose that these additional interactions, as
      well as the intrinsic stability of the carbamyl linkage, contribute to the
      extraordinary stability of the BlaC-NXL104 adduct.

PMID- 22587690
TI  - Effects of humanness and gender in voice processing.
AB  - When we observe a producible human movement, the brain performs a specific
      perception-action matching process, which possibly facilitates perceptual
      processing. In this work, we wanted to study whether the producibility of a sound
      affects the speed at which it is categorized. Participants were presented with
      isolated sounds, either sung by a natural male or female voice ('producible') or
      distorted by saturation ('non-producible'), and had to categorize them as
      produced by a voice or by a machine. We analyzed reaction time variations as a
      function of the gender and humanness of the voice. Results corroborate the
      existence of a 'human bias' in auditory perception, and suggest a processing
      speed asymmetry between natural female and male voices.

PMID- 22587691
TI  - Ultrasound guidance characteristics and efficiency of suprazygomatic maxillary
      nerve blocks in infants: a descriptive prospective study.
AB  - BACKGROUND: Bilateral suprazygomatic maxillary nerve blocks approach improves
      pain relief after palate surgery. We report the feasibility and efficiency of
      ultrasound-guided suprazygomatic maxillary nerve blocks in cleft palate repair in
      children. METHODS: Twenty-five children scheduled to undergo surgical cleft
      palate repair were included. Ultrasound-guided suprazygomatic maxillary blocks
      were performed according to landmarks previously defined. The ultrasound probe
      was located optimally over the maxilla and under the zygomatic bone to visualize
      the pterygopalatine fossa. 0.15.ml.kg(-1) of 0.2% ropivacaine was injected
      bilaterally. Feasibility of block, spread of local anesthetic, pain scores and
      side effects were noted. RESULTS: Fifty ultrasound-guided suprazygomatic
      maxillary nerve blocks were performed in 25 children. The needle movement was
      seen in all cases using an out-of-plane approach. The spread of LA was clearly
      observed in 94% (47/50) of cases. A poor ultrasound imaging was found in 4%
      (2/50), and the spread of LA was not identified in 2% of case (1/50). The median
      time to perform the block was 56 s (35-120 s). The median pain scores and
      consumption of nalbuphine were low during the study period. 80% of patients did
      not require continuous opioid infusion. No complication related to maxillary
      blocks was reported. CONCLUSION: With a very low technical failure rate and a
      good clinical success rate, ultrasound appears to be a useful and simple tool to
      aid suprazygomatic maxillary nerve block in children.

PMID- 22587692
TI  - Carbon-fiber tips for scanning probe microscopes and molecular electronics
      experiments.
AB  - We fabricate and characterize carbon-fiber tips for their use in combined
      scanning tunneling and force microscopy based on piezoelectric quartz tuning fork
      force sensors. An electrochemical fabrication procedure to etch the tips is used
      to yield reproducible sub-100-nm apex. We also study electron transport through
      single-molecule junctions formed by a single octanethiol molecule bonded by the
      thiol anchoring group to a gold electrode and linked to a carbon tip by the
      methyl group. We observe the presence of conductance plateaus during the
      stretching of the molecular bridge, which is the signature of the formation of a
      molecular junction.

PMID- 22587693
TI  - Environmental and genetic effects on yield and secondary metabolite production in
      Brassica rapa crops.
AB  - Twelve Brassica rapa varieties grown, such as turnip green and turnip top, were
      evaluated in seven environments to determine the environmental and genotypic
      variables that have an influence on crop production and on the content of
      glucosinolates and phenolic compounds. Factorial regression analysis showed that,
      in general, crop production was favored by high temperatures all along the crop
      cycle. However, the lack of a period of intense cold could be a limiting factor.
      The metabolite content seems to be regulated by extreme temperatures (daily
      maximum and minimum temperatures) rather than by average daily temperatures. With
      regard to genotypic covariables, turnip top production was significantly affected
      by traits related to the vegetative development and time to flowering. Meanwhile,
      turnip green production was largely affected by a sinapoyl derivative compound,
      which is a precursor of cell wall components. Cross-talk between glucosinolate
      biosynthesis and phenylpropanoid signaling pathways is suggested.

PMID- 22587694
TI  - Occupational health nursing in Spain.

PMID- 22587695
TI  - 2012 AAOHN Lillian G. Carter humanitarian Award winner: Joy E. Wachs, PhD, RN,
      FAAOHN.

PMID- 22587696
TI  - Time management for today's workplace demands.
AB  - As the work force decreases, the workload remains the same or, in many cases,
      increases. An effective employee must arrange work time to accomplish what needs
      to be done in the time available. The best way to manage time is to set a goal,
      develop a plan, and measure the outcome. To manage time requires determining
      where time is currently spent, taking time at the end of the day to prepare for
      the next morning, managing appointments, carefully planning projects, and
      managing phone, electronic, and paper mail. Organization is another step in
      effectively managing time. An organizational system decreases wasted time.
      Keeping the desk clear and creating a system to organize mail improves
      efficiency. Time management also focuses on balance, an overall purpose, and
      supporting principles. Personal or professional effectiveness does not depend
      solely on the effort expended, but whether the effort is in the right direction.
      The challenge of time management is to manage not only time, but also oneself.

PMID- 22587697
TI  - Nurse overtime, working conditions, and the presence of mandatory nurse overtime
      regulations.
AB  - Although more states have regulated mandatory nurse overtime, limited research
      has examined the impact of these regulations on the actual time nurses work and
      their working conditions. The purpose of this study was to compare nurse overtime
      and working conditions between states with and states without regulations
      limiting mandatory nurse overtime. Data were collected from registered nurses
      working in hospitals located in states with and without mandatory nurse overtime
      regulations; the final sample consisted of 219 nurses. No difference was found in
      overtime worked between nurses who worked in states with regulations or without.
      Those nurses working in states with regulations cared for more patients per shift
      and experienced more chronic nursing shortages on their nursing units than those
      working in states without regulation. Continuous efforts are needed to improve
      the implementation of regulations to reduce nurse mandatory overtime and long
      work hours.

PMID- 22587698
TI  - Mortality and cancer incidence in a copper-zinc cohort.
AB  - Previous studies of copper-zinc workers have primarily observed significant
      increases in lung and other respiratory cancers. This study concurrently examined
      cancer incidence and cause-specific mortality for a cohort of workers at a copper
      zinc producer in Ontario, Canada, from 1964 to 2005. Significant elevations in
      lung cancer incidence were observed for males in the overall cohort (standardized
      incidence ratio [SIR] = 124, 95% confidence interval [CI] = 102-150) and for
      surface mine (SIR = 272, 95% CI = 124-517), concentrator (SIR = 191, 95% CI = 102
      327), and central maintenance (SIR = 214, 95% CI = 125-343) employees.
      Significant elevations of non-Hodgkin's lymphoma incidence were observed for male
      underground mine employees (SIR = 232, 95% CI = 111-426). Occupational etiology
      cannot be ascertained with the current exploratory study design. Future studies
      could (1) incorporate exposure assessment for subgroups within the existing
      cohort and (2) determine the efficacy of wellness programs in partnership with
      the local health unit.

PMID- 22587701
TI  - Living well with chronic disease.
AB  - Occupational and environmental health nurses are well positioned to assist
      workers in living well with chronic disease.

PMID- 22587699
TI  - Pesticide exposure and child neurodevelopment: summary and implications.
AB  - Widely used around the world, pesticides play an important role in protecting
      health, crops, and property. However, pesticides may also have detrimental
      effects on human health, with young children among the particularly vulnerable.
      Recent research suggests that even low levels of pesticide exposure can affect
      young children's neurological and behavioral development. Evidence shows a link
      between pesticides and neonatal reflexes, psychomotor and mental development, and
      attention-deficit hyperactivity disorder. Implications include a need for
      improved risk assessment and health histories by clinicians, greater education at
      all levels, more common use of integrated pest management, and continued policy
      and regulatory strategies to mitigate the effects of and the need for pesticides.

PMID- 22587702
TI  - Structural evolution of BaTiO(3) nanocrystals synthesized at room temperature.
AB  - Sub-10 nm BaTiO(3) nanocrystals were synthesized at room temperature via the
      vapor diffusion sol-gel method, and their structural evolution during nucleation
      and growth stages was followed using a series of techniques that probe the atomic
      structure on different length and time scales. Special emphasis was placed on
      assessing the evolution of the local symmetry and structural coherence of the
      resulting nanocrystals, as these are the structural bases for cooperative
      properties such as ferroelectricity. Although the room-temperature crystal
      structure of the fully grown nanocrystals appears cubic to Rietveld analysis of
      synchrotron X-ray diffraction data, Raman spectroscopy and pair distribution
      function analysis demonstrate the presence of non-centrosymmetric regions arising
      from the off-centering of the titanium atoms. This finding demonstrates that
      accounting for diffuse scattering is critical when attempting the structural
      characterization of nanocrystals with X-ray diffraction. The local symmetry of
      acentric regions present in BaTiO(3) nanocrystals, particularly structural
      correlations within an individual unit cell and between two adjacent unit cells,
      is best described by a tetragonal P4mm space group. The orthorhombic Amm2 space
      group also provides an adequate description, suggesting both types of local
      symmetry can coexist at room temperature. The average magnitude of the local off
      center displacements of the titanium atoms along the polar axis is comparable to
      that observed in bulk BaTiO(3), and their coherence length is on the order of 16
      A. The presence of local dipoles suggests that a large amount of macroscopic
      polarization can be achieved in nanocrystalline BaTiO(3) if the coherence of
      their ferroelectric coupling is further increased.

PMID- 22587703
TI  - Cucurbituril adamantanediazirine complexes and consequential carbene chemistry.
AB  - Adamantanediazirines, precursors of adamantanylidenes, form 1:1 complexes (guest
      to host) with cucurbit[7]uril and cucurbit[8]uril and a 3:1 complex with a Pd
      nanocage in water. (1)H NMR spectra suggested that these complexes are stable in
      water on the NMR time scale. While photolysis of adamantanediazirines in water
      gave mainly adamantanone and adamantanol via adamantanylidene as intermediate,
      the 1:1 complexes of adamantanediazirine with cucurbiturils gave intramolecular C
      H insertion products of adamantanylidene in >90% yield. The study establishes
      that significant control of carbene reactivity can be achieved when the precursor
      is encapsulated within a tight inert cavity. While the general characteristics of
      molecular containers can be understood on the basis of concepts such as
      "confinement" and "weak interactions", each one is unique and deserves careful
      scrutiny.

PMID- 22587704
TI  - Prediction of a novel RNA binding domain in crocodilepox Zimbabwe Gene 157.
AB  - BACKGROUND: Although the crocodilepox virus (CRV) is currently unclassified,
      phylogenetic analyses suggest that its closest known relatives are molluscum
      contagiosum virus (MCV) and the avipox viruses. The CRV genome is approximately
      190 kb and contains a large number of unique genes in addition to the set of
      conserved Chordopoxvirus genes found in all such viruses. Upon sequencing the
      viral genome, others noted that this virus was also unusual because of the lack
      of a series of common immuno-suppressive genes. However, the genome contains
      multiple genes of unknown function that are likely to function in reducing the
      anti-viral response of the host. RESULTS: By using sensitive database searches
      for similarity, we observed that gene 157 of CRV-strain Zimbabwe (CRV-ZWE)
      encodes a protein with a domain that is predicted to bind dsRNA. Domain
      characterization supported this prediction, therefore, we tested the ability of
      the Robetta protein structure prediction server to model the amino acid sequence
      of this protein on a well-characterized RNA binding domain. The model generated
      by Robetta suggests that CRV-ZWE-157 does indeed contain an RNA binding domain;
      the model could be overlaid on the template protein structure with high
      confidence. CONCLUSION: We hypothesize that CRV-ZWE-157 encodes a novel poxvirus
      RNA binding protein and suggest that as a non-core gene it may play a role in
      host-range determination or function to dampen host anti-viral responses.
      Potential targets for this CRV protein include the host interferon response and
      miRNA pathways.

PMID- 22587705
TI  - Transcription activator-like effector proteins induce the expression of the
      frataxin gene.
AB  - Genes encoding transcription activator-like effector (TALE) proteins may be
      engineered to target specific DNA sequences. TALEs fused with a transcription
      activator can be used to specifically induce the expression of a gene. This could
      lead to completely new therapies for several diseases. We have applied this
      potential therapeutic approach to Friedreich ataxia (FRDA), as an example. FRDA
      is due to reduced expression of frataxin because of elongation of a trinucleotide
      (GAA) repeat in intron 1. Our aim was to develop a potential treatment for FRDA
      by increasing the expression of the frataxin gene. We engineered 12 TALE genes
      (TALE(Frat)) encoding TALE(Frat) proteins, each specifically targeting different
      14-bp DNA sequences within the proximal region of the human frataxin promoter.
      When the genes encoding these TALE(Frat) proteins were fused with a transcription
      activator, that is, four VP16 peptides (i.e., VP64), the resulting TALE(Frat)
      VP64 proteins induced the expression of an mCherry reporter gene fused to a mini
      cytomegalovirus promoter able to be activated by the insertion of the frataxin
      proximal promoter upstream to the minipromoter. These TALE(Frat)-VP64 proteins
      also increased, by 2- to 3-fold, frataxin gene expression (detected by qRT-PCR)
      in the cells. We conclude that TALE(Frat) proteins targeting the frataxin
      promoter may be used to increase the expression of frataxin mRNA and potentially
      could alleviate the symptoms of Friedreich ataxia. TALE methodology opens a new
      field of research, which could be used to develop TALE proteins to treat other
      diseases by inducing the expression of specific genes.

PMID- 22587706
TI  - Molecular characterization of swine leukocyte antigen gene diversity in purebred
      Pietrain pigs.
AB  - The porcine major histocompatibility complex (MHC) harbors the highly polymorphic
      swine leukocyte antigen (SLA) class I and II gene clusters encoding glycoproteins
      that present antigenic peptides to T cells in the adaptive immune response. In
      Austria, the majority of commercial pigs are F 2 descendants of F 1 Large
      White/Landrace hybrids paired with Pietrain boars. Therefore, the repertoire of
      SLA alleles and haplotypes present in Pietrain pigs has an important influence on
      that of their descendants. In this study, we characterized the SLA class I ( SLA
      1 , SLA-2 , SLA-3 ) and class II ( SLA-DRB1 , SLA-DQB1 , SLA-DQA ) genes of 27
      purebred Pietrain pigs using a combination of the high-resolution sequence-based
      typing (SBT) method and a low-resolution (Lr) PCR-based method using allele
      group, sequence-specific primers (PCR-SSP). A total of 15 class I and 13 class II
      haplotypes were identified in the studied cohort. The most common SLA class I
      haplotype Lr-43.0 ( SLA-1 *11XX- SLA-3 *04XX- SLA-2 *04XX) was identified in 11
      animals with a frequency of 20%. For SLA class II, the most prevalent haplotype,
      Lr-0.14 [ SLA-DRB1 *0901- SLA-DQB1 *0801- SLA-DQA *03XX], was found in 14 animals
      with a frequency of 26%. Two class II haplotypes, tentatively designated as Lr
      Pie-0.1 [ SLA-DRB1 *01XX/be01/ha04- SLA-DQB1 *05XX- SLA - DQA*blank] and Lr-Pie
      0.2 [ SLA-DRB1 *06XX- SLA-DQB1 *03XX- SLA-DQA *03XX], appeared to be novel and
      have never been reported so far in other pig populations. We showed that SLA
      genotyping using PCR-SSP-based assays represents a rapid and cost-effective way
      to study SLA diversity in outbred commercial pigs and may facilitate the
      development of more effective vaccines or identification of disease-resistant
      pigs in the context of SLA antigens to improve overall swine health.

PMID- 22587707
TI  - Multiple Pappenheimer bodies after splenectomy.

PMID- 22587708
TI  - Inhibition of MMP-9 by a selective gelatinase inhibitor protects neurovasculature
      from embolic focal cerebral ischemia.
AB  - BACKGROUND: Cerebral ischemia has been shown to induce activation of matrix
      metalloproteinases (MMPs), particularly MMP-9, which is associated with
      impairment of the neurovasculature, resulting in blood-brain barrier breakdown,
      hemorrhage and neurodegeneration. We previously reported that the thiirane
      inhibitor SB-3CT, which is selective for gelatinases (MMP-2 and -9), could
      antagonize neuronal apoptosis after transient focal cerebral ischemia. RESULTS:
      Here, we used a fibrin-rich clot to occlude the middle cerebral artery (MCA) and
      assessed the effects of SB-3CT on the neurovasculature. Results show that
      neurobehavioral deficits and infarct volumes induced by embolic ischemia are
      comparable to those induced by the filament-occluded transient MCA model.
      Confocal microscopy indicated embolus-blocked brain microvasculature and neuronal
      cell death. Post-ischemic SB-3CT treatment attenuated infarct volume, ameliorated
      neurobehavioral outcomes, and antagonized the increases in levels of proform and
      activated MMP-9. Embolic ischemia caused degradation of the neurovascular matrix
      component laminin and tight-junction protein ZO-1, contraction of pericytes, and
      loss of lectin-positive brain microvessels. Despite the presence of the embolus,
      SB-3CT mitigated these outcomes and reduced hemorrhagic volumes. Interestingly,
      SB-3CT treatment for seven days protected against neuronal laminin degradation
      and protected neurons from ischemic cell death. CONCLUSION: These results
      demonstrate considerable promise for the thiirane class of selective gelatinase
      inhibitors as potential therapeutic agents in stroke therapy.

PMID- 22587710
TI  - Theoretical study on polynuclear superalkali cations with various functional
      groups as the central core.
AB  - A new series of polynuclear superalkali cations YLi(3)(+) (Y = CO(3), SO(3),
      SO(4), O(4), and O(5)) has been created when the central group is surrounded by
      alkali atoms. The structural characteristics and stabilities of these systems are
      provided on the basis of ab initio methods. In the lowest-energy structure of the
      CO(3)Li(3)(+), SO(3)Li(3)(+), and SO(4)Li(3)(+) cations, the central Y (Y =
      CO(3), SO(3), and SO(4)) group features a slight distortion. The global minima of
      O(4)Li(3)(+) and O(5)Li(3)(+) are of the forms O(2)(-)(Li(+))(3)O(2)(-) and O(2)(
      )(Li(+))(3)O(3)(-), respectively, both of which contain two monovalent ion units.
      The structural integrity of the central Y group and the arrangement of the
      lithium ligands are two influencing factors on the vertical electron affinities
      (EA(vert)) for the YLi(3)(+) species. The YLi(3)(+) cation, with its lithium
      ligands being distributed evenly or far from each other, tends to exhibit a low
      EA(vert) value, whereas a greater extent of cleavage of the central Y group leads
      to a higher EA(vert) value and even makes some species lose their superalkali
      nature.

PMID- 22587709
TI  - Executive function predicts adaptive behavior in children with histories of heavy
      prenatal alcohol exposure and attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: Prenatal exposure to alcohol often results in disruption to discrete
      cognitive and behavioral domains, including executive function (EF) and adaptive
      functioning. In the current study, the relation between these 2 domains was
      examined in children with histories of heavy prenatal alcohol exposure,
      nonexposed children with a diagnosis of attention-deficit/hyperactivity disorder
      (ADHD), and typically developing controls. METHODS: As part of a multisite study,
      3 groups of children (8 to 18 years, M = 12.10) were tested: children with
      histories of heavy prenatal alcohol exposure (ALC, n = 142), nonexposed children
      with ADHD (ADHD, n = 82), and typically developing controls (CON, n = 133) who
      did not have ADHD or a history of prenatal alcohol exposure. Children completed
      subtests of the Delis-Kaplan Executive Function System (D-KEFS), and their
      primary caregivers completed the Vineland Adaptive Behavior Scales-II. Data were
      analyzed using regression analyses. RESULTS: Analyses showed that EF measures
      were predictive of adaptive abilities, and significant interactions between D
      KEFS measures and group were present. For the ADHD group, the relation between
      adaptive abilities and EF was more general, with 3 of the 4 EF measures showing a
      significant relation with adaptive score. In contrast, for the ALC group, this
      relation was specific to the nonverbal EF measures. In the CON group, performance
      on EF tasks did not predict adaptive scores over the influence of age.
      CONCLUSIONS: These results support prior research in ADHD, suggesting that EF
      deficits are predictive of poorer adaptive behavior and extend this finding to
      include children with heavy prenatal exposure to alcohol. However, the relation
      between EF and adaptive ability differed by group, suggesting unique patterns of
      abilities in these children. These results provide enhanced understanding of
      adaptive deficits in these populations, as well as demonstrate the ecological
      validity of laboratory measures of EF.

PMID- 22587711
TI  - Highly enantioselective synthesis of chiral allenes by sequential creation of
      stereogenic center and chirality transfer in a single pot operation.
AB  - Chiral allenes are readily accessed in a single pot operation in the reaction of
      terminal alkynes, aldehydes, chiral secondary amines, and zinc halides in good
      yields (up to 77% yield) and excellent enantioselectivities (up to 99% ee) in
      toluene at 120  degrees C. The reaction proceeds through initial formation of
      chiral propargylamine intermediates with creation of a new stereogenic center and
      subsequent chirality transfer via an intramolecular hydride shift to produce
      chiral allenes with high enantiomeric purities.

PMID- 22587712
TI  - Heart rate monitors: state of the art.
AB  - Heart rate is a useful indicator of physiological adaptation and intensity of
      effort. Therefore, heart rate monitoring is an important component of
      cardiovascular fitness assessment and training programmes. The electrocardiogram
      (ECG) and Holter monitoring devices are accurate, but they are not appropriate
      for use in field settings due to cost, size and complexity of operation.
      Lightweight telemetric heart rate monitors equipped with conventional electrodes
      have been available since 1983 and have been shown to be accurate and valid tools
      for heart rate monitoring and registering in the field. Polar Electro Oy has been
      at the forefront of ambulatory heart rate monitor technology for 15 years. This
      paper reviews the development of Polar heart rate monitors and their measurement
      accuracy compared to Holter ECG devices at rest and during exercise, both in
      adults and in children.

PMID- 22587713
TI  - Young people's physical activity patterns as assessed by heart rate monitoring.
AB  - Physical activity is a complex behaviour and the accurate assessment of young
      people's physical activity patterns is extremely difficult. Ideally, a
      combination of different techniques should be used. For example, the simultaneous
      use of doubly labelled water, heart rate monitoring and structured observation
      would yield information on total energy expenditure, patterns of relative
      physiological load (intensity) on the cardiopulmonary system, and the frequency,
      duration and type of physical activity experienced. However, the choice of
      method(s) is likely to be dictated by cost and logistics and heart rate
      monitoring alone has provided some valuable insights into young people's physical
      activity patterns. Sustained periods of moderate to vigorous physical activity
      are not characteristic of either children's or adolescents' physical activity
      patterns. Boys appear to be more active than girls from an early age and,
      although both males and females generally reduce their level of physical activity
      as they move from childhood through adolescence and into adult life, the rate of
      decline is greater in girls. Some children and adolescents are physically active,
      but many young people have adopted sedentary lifestyles.

PMID- 22587714
TI  - Longitudinal relationships between resting heart rate and biological risk factors
      for cardiovascular disease: the Amsterdam Growth and Health Study.
AB  - The aim of this study was to analyse longitudinal relationships between resting
      heart rate and biological risk factors for cardiovascular disease using data from
      the longitudinal Amsterdam Growth and Health Study (AGHS). In the AGHS, 98
      females and 81 males were measured six times between 1977 and 1991. In 1977, the
      age of the subjects was 13 years. The variables assessed included resting heart
      rate, diastolic and systolic blood pressure, high-density serum lipoprotein,
      total serum cholesterol, the sum of four skinfolds, cardiopulmonary fitness (VO 2
      max), habitual physical activity and smoking history. To investigate the
      longitudinal relationships between resting heart rate and diastolic blood
      pressure, systolic blood pressure, high-density serum lipoprotein, total serum
      cholesterol, sum of four skinfolds and V O 2 max, generalized estimating
      equations were used, leading to one standardized longitudinal regression
      coefficient (beta). Significant univariate relationships were found between
      resting heart rate and diastolic blood pressure (beta = 0.142; P = 0.00),
      systolic blood pressure (beta = 0.134; P = 0.00), VO 2 max (beta = -0.091; P =
      0.00) and sum of four skinfolds (beta = 0.047; P = 0.021). The relationships
      between resting heart rate and diastolic blood pressure, systolic blood pressure
      and VO 2 max did not change substantially when corrected for habitual physical
      activity and smoking history. The relationship between resting heart rate and sum
      of four skinfolds was no longer found to be significant when corrected for
      habitual physical activity and smoking history. For these relationships, no
      interaction between resting heart rate and sex was found.

PMID- 22587715
TI  - Experiences of heart rate monitoring in observational and intervention studies.
AB  - Scientific demonstration of the health-enhancing eff ects, and the cardiovascular
      risks, of regular physical activity has created a need to characterize, in a
      quantitative manner, the intensity of physical activity in its various forms.
      Heart rate is one useful indicator because of its known predictable and
      reproducible relationships, within certain limits, to energy expenditure and
      cardiac load or strain. The development of versatile ambulatory heart rate
      monitoring devices expands the possibilities to assess the intensity and cardiac
      strain of various types of physical activity in natural settings. The examples
      cited in this paper demonstrate that ambulatory heart rate monitoring is an
      accurate, reliable, non-obtrusive and socially acceptable technique in a variety
      of conditions. It is relatively inexpensive and easy to use by both the
      experimental subjects and the research personnel, and it provides large amounts
      of data for versatile processing and display by ordinary equipment.

PMID- 22587716
TI  - A natural history of athleticism, health and longevity.
AB  - Longitudinal observations on the sports play, social habits and health status of
      52,000 men who entered Harvard College or the University of Pennsylvania between
      1916 and 1950 have afforded means of identifying causes of disease and death.
      These observations were then translated into the eff ect of sports and physical
      exercise on health and longevity. Student sports play in college predicted a
      decreased risk of developing cardiovascular disease (CVD) at least up to age 50
      years. Questionnaire surveys showed physical exercise (sports play, walking and
      stair climbing) in middle age to be inversely related to the later development of
      CVD and early death. In a 10-year follow-up between 1962 and 1972, alumni aged 35
      74 years who expended greater than or equal to >= 2000 kcal week(-1) (8.4 MJ week
      -1 ) in such activities had a 25% reduced risk of CVD and death compared with
      less active men. But, the 'protective eff ect' of early athleticism waned unless
      a physically active life was maintained. In contrast, sedentary students who took
      up an active life were at a lower risk of CVD and death than former student
      athletes who gave up or reduced their physical activities in middle age. A total
      of 17,815 Harvard alumni aged 45-84 years were followed from a 1977 questionnaire
      survey through 1992, with 4399 deaths occurring. Death rates declined with
      increased levels of total activity (estimated in kilocalories), and declined also
      with increased intensity of effort measured as from none, to light, to moderately
      vigorous or vigorous sports play. Death rates at any given quantity of physical
      exercise were lower for men playing moderately intense sports than for less
      vigorous men. Over the age range, in the 16-year follow-up, Harvard alumni
      playing moderately vigorous or more intense sports gained 1.5 years by age 90
      compared with less active men.

PMID- 22587717
TI  - Cardiorespiratory fitness determined by exercise heart rate as a predictor of
      mortality in the Aerobics Center Longitudinal Study.
AB  - This paper reviews the association of cardiorespiratory fitness to all-cause and
      cardiovascular disease mortality. Data are presented from the Aerobics Center
      Longitudinal Study (ACLS), which is a prospective study of 25,341 men and 7080
      women. These individuals completed a health screening examination and were
      followed for more than 8 years for mortality. Low cardiorespiratory fitness was
      one of the strongest predictors of mortality in this study, with the risk of low
      fitness being comparable to smoking. Risk of low fitness persisted after
      adjustment for a long list of other risk factors and other potential confounders.
      Previously unpublished data on metabolic and cardiovascular responses to the
      exercise test used in the ACLS are also provided. This additional information
      further characterizes this cohort, and gives additional data and methods that can
      be used by others for risk assessment and stratification.

PMID- 22587718
TI  - Rehabilitation of cardiac patients in the twenty-first century: changing
      paradigms and perceptions.
AB  - Rehabilitation of the coronary patient has changed dramatically over the past 40
      years. The deleterious effects of prolonged bed rest have prompted the
      liberalization of activity soon after an acute cardiac event. Exercise-based
      cardiac rehabilitation has been shown to provide a 20-24% reduction in total and
      cardiovascular-related mortality. Adjunctive upper body aerobic exercise and mild
      to moderate resistance training can improve muscular strength and endurance in
      clinically stable coronary patients and attenuate the cardiovascular demands of
      occupational and leisure-time activities. Risk stratification has emerged as the
      centrepiece of strategies aimed at stabilizing or enhancing the clinical status
      of post-myocardial infarction patients, as well as vocational counselling.
      Moreover, randomized controlled trials have confirmed the hypothesis that lipid
      lowering is associated with, and possibly preceded by, plaque stabilization and a
      reduction in the risk of recurrent cardiac events.

PMID- 22587719
TI  - Submaximal markers of exercise intensity.
AB  - Numerous approaches have been used to improve the science and art of exercise
      prescription, and particular challenges exist in the prescription of exercise
      intensity. Traditionally, work in the area has been the province of exercise
      physiologists interested in the improvement of training programmes for athletes,
      as opposed to the more widespread recent interest in health-related fitness and
      physical activity for all. The generalized approach to the provision of
      guidelines for exercise prescription has meant that individuals have, at best,
      prediction equations which provide a wide band of heart rate between which they
      can work to derive health benefits. This paper explores some of the commonly
      employed submaximal markers of exercise intensity and proposes a number of
      approaches for improvements beyond generalized equations.

PMID- 22587720
TI  - Physiological and metabolic responses to increasing work rates: relevance for
      exercise prescription.
AB  - Interest in rises in oxygen consumption (VO2) with increasing exercise intensity
      largely originate from the work of Hill and colleagues in the 1920s. Their
      studies led to a belief that cardiac output and VO2 'plateau' at increasing work
      rates and that muscle hypoxia leads to fatigue. Hence, it was assumed that the
      primary benefit of exercise training is to increase muscle oxidative capacity and
      that the greatest benefit of training would occur at work rates around the
      'anaerobic threshold'. In this paper, we question whether working muscles become
      hypoxic at high work rates. Rather than being a threshold response to hypoxia, we
      propose that plasma lactate accumulation and curvilinear rises in ventilation at
      high work rates are both independent consequences of the acceleration of
      carbohydrate metabolism with increasing exercise intensity. Evidence is also
      presented to suggest that athletic performances are not exclusively related to
      muscle oxidative capacity. Once an athlete has adapted to prolonged, 'aerobic'
      training, intervals of 'anaerobic', high-intensity exercise further improve
      performance without additional increases in muscle mitochondrial density or
      alterations in metabolism. Until the mechanisms underlying the latter
      improvements in performance are understood, it is difficult to advise athletes on
      how best to prepare for competition.

PMID- 22587721
TI  - Heart rate during training and competition for long-distance running.
AB  - Heart rate monitors are used widely by scientists, coaches and sports
      participants to monitor heart rate during physical activity. Although there are
      data that show that heart rate monitors measure heart rate accurately during a
      range of physical activities, there is less consensus on the interpretation of
      heart rate data. The day-to-day variation in heart rate under controlled
      submaximal exercise conditions is approximately 6 beats min (-1), which is
      generally less than the decrease in the submaximal heart rate that results from
      endurance training. A bout of exercise that causes moderate dehydration can
      affect heart rate during submaximal exercise. It has been estimated that, for
      every 1% loss in body weight due to dehydration, heart rate increases by 7 beats
      min (-1). During a 10-km race, the heart rate is approximately 20 beats min (-1)
      higher at racing pace compared to the heart rate at the same running speed under
      non-competitive conditions. In conclusion, heart rate monitors measure heart rate
      accurately under diverse conditions, and have the potential to be regarded as
      'ergogenic aids'. However, further scientific studies are needed before the heart
      rate data can be interpreted accurately and used to improve long-distance running
      performance.

PMID- 22587722
TI  - Heart rate monitoring during training and competition in cyclists.
AB  - To obtain optimal training effects and avoid overtraining, it is necessary to
      monitor the intensity of training. In cycling, speed is not an accurate indicator
      of exercise intensity, and therefore alternatives have to be found to monitor
      exercise intensity during training and competition. Power output may be the most
      direct indicator, but heart rate is easier to monitor and measure. There are,
      however, limitations that have to be taken into account when using a heart rate
      monitor. For example, the position on the bicycle may change heart rate at a
      given exercise intensity. More important, however, is the increase in heart rate
      over time, a phenomenon described as 'cardiac drift'. Cardiac drift can change
      the heart rate-power output relationship drastically, especially in hot
      environments or at altitude. It is important to determine whether one is
      interested in monitoring exercise intensity per se or measuring whole-body
      stress. Power output may be a better indicator of the former and heart rate may,
      under many conditions, be a better indicator of the latter. Heart rate can be
      used to evaluate a cyclist after training or competition, or to determine the
      exercise intensity during training. Heart rate monitoring is very useful in the
      detection of early overtraining, especially in combination with lactate curves
      and questionnaires. During overtraining, maximal heart rates as well as
      submaximal heart rates may be decreased, while resting and, in particular,
      sleeping - heart rates may be increased.

PMID- 22587723
TI  - Heart rate monitoring and exercise: challenges for the future.
AB  - In little over a decade, lightweight radiotelemetric equipment has been designed
      and developed which measures heart rate accurately under free-living conditions.
      The rate of refinement of the heart rate monitor technology has far exceeded the
      rate at which the understanding of heart rate during exercise has improved. This
      brief paper lists the problems and questions that need to be addressed to improve
      our understanding and application of heart rate measured during exercise to
      optimize exercise prescription for health and sports performance.

PMID- 22587724
TI  - Daily texting improves birth control pill adherence.

PMID- 22587725
TI  - Scanning tunneling spectroscopy of epitaxial graphene nanoisland on Ir(111).
AB  - Scanning tunneling spectroscopy (STS) was used to measure local differential
      conductance (dI/dV) spectra on nanometer-size graphene islands on an Ir(111)
      surface. Energy resolved dI/dV maps clearly show a spatial modulation, which we
      ascribe to a modulated local density of states due to quantum confinement. STS
      near graphene edges indicates a position dependence of the dI/dV signals, which
      suggests a reduced density of states near the edges of graphene islands on
      Ir(111).

PMID- 22587726
TI  - Establishing a toolkit for precursor-directed polyketide biosynthesis: exploring
      substrate promiscuities of acid-CoA ligases.
AB  - Polyketides are chemically diverse and medicinally important biochemicals that
      are biosynthesized from acyl-CoA precursors by polyketide synthases. One of the
      limitations to combinatorial biosynthesis of polyketides has been the lack of a
      toolkit that describes the means of delivering novel acyl-CoA precursors
      necessary for polyketide biosynthesis. Using five acid-CoA ligases obtained from
      various plants and microorganisms, we biosynthesized an initial library of 79
      acyl-CoA thioesters by screening each of the acid-CoA ligases against a library
      of 123 carboxylic acids. The library of acyl-CoA thioesters includes derivatives
      of cinnamyl-CoA, 3-phenylpropanoyl-CoA, benzoyl-CoA, phenylacetyl-CoA, malonyl
      CoA, saturated and unsaturated aliphatic CoA thioesters, and bicyclic aromatic
      CoA thioesters. In our search for the biosynthetic routes of novel acyl-CoA
      precursors, we discovered two previously unreported malonyl-CoA derivatives (3
      thiophenemalonyl-CoA and phenylmalonyl-CoA) that cannot be produced by canonical
      malonyl-CoA synthetases. This report highlights the utility and importance of
      determining substrate promiscuities beyond conventional substrate pools and
      describes novel enzymatic routes for the establishment of precursor-directed
      combinatorial polyketide biosynthesis.

PMID- 22587727
TI  - The taxonomic status of Trichophyton quinckeanum and T. interdigitale revisited:
      a multigene phylogenetic approach.
AB  - Trichophyton quinckeanum, known as the causative agent of mouse favus, has been a
      subject of controversy since its discovery, 125 years ago. The purpose of this
      study was to examine the phylogenetic relationships between this fungus and
      related taxa. To achieve this objective, the ITS rDNA region, as well as actin
      and beta-tubulin gene regions of various isolates were sequenced. Bayesian
      inference and maximum likelihood analyses were conducted with T. rubrum as
      outgroup. Our study showed that strains identified as T. quinckeanum and others
      identified as T. schoenleinii are part of the complex T. mentagrophytes, and that
      their genotype cannot be confused with any other dermatophytes. Furthermore, this
      study demonstrates that the choice of the neotype of T. mentagrophytes was
      inappropriate. The beta-tubulin topology also revealed that isolates of T.
      interdigitale form a genetically distinct population from the type strains of
      Arthroderma vanbreuseghemii. Therefore, contrary to what is generally accepted,
      the anthropophilic species T. interdigitale cannot be considered as the anamorph
      associated with the latter.

PMID- 22587729
TI  - Evaluation of fungal-specific fluorescent labeled echinocandin probes as
      diagnostic adjuncts.
AB  - The diagnosis of invasive fungal infections from radiographic imaging is non
      specific and problematic. As a first step toward increasing specificity, we
      describe the development of a broad-spectrum fungal-specific targeting molecule,
      which when modified with a fluorescent label fully retains its targeting
      properties, and provides a basis for future imaging applications.

PMID- 22587728
TI  - Amphotericin B in vitro resistance is associated with fatal Aspergillus flavus
      infection.
AB  - Whether in vitro antifungal susceptibility findings correlate with the outcome of
      patients with invasive aspergillosis (IA) remains debated. This study aimed to
      test whether IA patients' outcomes were associated with in vitro susceptibility
      results. To do so, we determined the in vitro susceptibility to amphotericin B
      (AMB) of 37 Aspergillus flavus isolates from 14 patients with haematological
      malignancies diagnosed with proven or probable IA, of which 13 were treated with
      AMB deoxycholate. Minimal inhibitory concentrations (MICs) were determined by
      Etest with the isolates classified as in vitro sensitive (AMB-S) or resistant
      (AMB-R) if their MICs were < 2 or >= 2 mg/l, respectively. The association of the
      patients' death with primary disease, administered antifungal treatment, and
      infection with AMB-R A. flavus was tested using generalized estimating equations
      logistic regression. We assessed AMB-R in 31/37 (84%) isolates. In the patients
      treated with AMB, the survival rate was 2/3 (67%) and 2/9 (22%) for those
      infected with AMB-S or AMB-R A. flavus, respectively. Both infection with AMB-R
      A. flavus (P = 0.014) strain and acute myelocytic leukaemia as the underlying
      primary disease (P = 0.036) were independent predictors of death. Our findings
      indicate that in vitro resistance predicts a poor outcome in patients with A.
      flavus invasive disease treated with AMB. Recent advances in non-culture-based
      microbiological methods should not discourage efforts to obtain in vitro
      antifungal susceptibility results, which are critical for the choice of
      antifungal therapy in patients with IA.

PMID- 22587730
TI  - Molecular epidemiology of dermatophytosis in Tehran, Iran, a clinical and
      microbial survey.
AB  - In the framework of a survey on dermatophytoses, 14,619 clinical specimens taken
      from outpatients with symptoms suggestive of tinea and referred to a Medical
      Mycology laboratory in Tehran, Iran, were analyzed by direct microscopy and
      culture. In total, 777 dermatophyte strains recovered in culture were randomly
      identified by a formerly established RFLP analysis method based on the rDNA ITS
      regions. For confirmation of species identification, 160 isolates representing
      the likely entire species spectrum were subjected to ITS-sequencing. Infection
      was confirmed in 5,175 collected samples (35.4%) by direct microscopy and/or
      culture. Tinea pedis was the most prevalent type of infection (43.4%), followed
      by tinea unguium (21.3%), tinea cruris (20.7%), tinea corporis (9.4%), tinea
      manuum (4.2%), tinea capitis (0.8%) and tinea faciei (0.2%). Trichophyton
      interdigitale was the most common isolate (40.5%) followed by T. rubrum (34.75%),
      Epidermophyton floccosum (15.6%), Microsporum canis (3.9%), T. tonsurans (3.5 %)
      and M. gypseum (0.5%). Other species included M. ferrugineum, T. erinacei, T.
      violaceum, T. schoenleinii, and a very rare species T. eriotrephon (each one
      0.25%). The two strains of T. eriotrephon isolated from tinea manuum and tinea
      faciei are the second and third reported cases worldwide. Application of DNA
      based methods is an important aid in monitoring trends in dermatophytosis in the
      community.

PMID- 22587731
TI  - Renal mucormycosis complicating extracorporeal membrane oxygenation.
AB  - Zygomycosis can manifest as severe infections, particularly in immunocompromised
      patients, which can be nosocomial in nature resulting from complications of
      invasive procedures. We report the case of a 65-year-old woman with a medical
      history of unclassified inflammatory rheumatism who underwent arteriovenous
      extracorporeal membrane oxygenation because of a myocardial failure following the
      drainage of a tuberculous tamponade. This procedure was complicated by a
      superinfection of the scarpa which revealed a disseminated zygomycosis with renal
      involvement. A favorable outcome was achieved after 15 months of antifungal
      therapy involving the use of liposomal amphotericin B followed with posaconazole
      which involved the close monitoring of the concentrations of this antifungal.
      Extracorporeal membrane oxygenation is a frequent procedure which could be
      complicated with severe fungal nosocomial infections such as zygomycosis. The
      outcome of such complication can be favorable with the utilization of new
      antifungal therapies.

PMID- 22587732
TI  - Candida albicans adhesion to human epithelial cells and polystyrene and formation
      of biofilm is reduced by sub-inhibitory Melaleuca alternifolia (tea tree)
      essential oil.
AB  - This study investigated the effects of the volatile terpene-rich oil from
      Melaleuca alternifolia (tea tree oil) on the formation of biofilms and the
      adhesion of C. albicans cells to both biotic and abiotic surfaces. Biofilm
      formation on polystyrene was significantly inhibited for 70% of the isolates at
      the lowest test concentration of 0.016% of tea tree oil (TTO) when quantified by
      XTT and 40% of isolates when measured by crystal violet staining. Adhesion to
      polystyrene, quantified by crystal violet staining, was significantly reduced for
      3 isolates at 0.031%, 6 isolates at 0.062% and 0.125% and for all 7 isolates at
      0.25% TTO. Reductions in adhesion were not due to loss of viability (at
      concentrations of <= 0.125%) or interactions between the TTO and polystyrene.
      Similarly, adhesion to buccal epithelial and HeLa cells was also significantly
      reduced in the presence of 0.016-0.062% TTO. Treatment with 0.125% TTO, but not
      0.062%, decreased the cell surface hydrophobicity of C. albicans, indicating one
      potential mechanism by which adhesion may be reduced. These data demonstrate that
      sub-inhibitory TTO reduces the adhesion of C. albicans to both human cells and
      polystyrene, inhibits biofilm formation and decreases cell surface
      hydrophobicity.

PMID- 22587733
TI  - Vaccination with mannan protects mice against systemic aspergillosis.
AB  - Invasive aspergillosis is a major cause of mortality in immunocompromised
      patients and therapeutic options are often limited, thus a vaccine would be
      desirable. We presently studied acid-stable cell-wall mannan (alpha-1, 6-linked
      backbone highly branched with alpha-1, 2; alpha-1, 3; and beta-1, 2-linked manno
      oligomers) derived from C. albicans, with or without conjugation to bovine serum
      albumin (BSA), as a vaccine against systemic aspergillosis. Mice were vaccinated
      subcutaneously with mannan or mannan-BSA conjugate weekly 3 times, ending 2 weeks
      prior to infection with A. fumigatus conidia. Results showed that the protection
      induced by mannan is dose-dependent; 12 mg unconjugated mannan alone or > 0.3 mg
      mannan-BSA consistently enhanced survival (P < 0.05). Fungal burdens in brains
      and kidneys were reduced after > 0.3 mg of mannan-BSA (all P < 0.05). Mannan
      induced protection was improved about 40-fold by conjugation of BSA to mannan.
      Mannan-BSA (500 kDa) was more protective than 40 kDa mannan-BSA. Mannan is a
      candidate for a cross-protective conjugate fungal vaccine.

PMID- 22587734
TI  - Screening by pulse CO-oximetry for environmental tobacco smoke exposure in
      preanesthetic children.
AB  - OBJECTIVE: The purpose of this study was to evaluate the ability of multiple
      wavelength pulse CO-oximetry (SpCO) to screen for environmental tobacco smoke
      (ETS) exposure in children. BACKGROUND: Exposure to ETS is associated with an
      increased risk of perioperative respiratory complications in children. It is
      often difficult to obtain an accurate history for ETS exposure, so a preoperative
      screening tool is desirable. Carbon monoxide is a measurable product of tobacco
      combustion. Multiple wavelength pulse CO-oximetry is a recently developed point
      of-care monitor. METHODS: Following IRB approval and parental consent, 220
      children aged 1-16 years having outpatient surgical procedures were enrolled.
      SpCO was measured preoperatively three times with the Radical-7 Rainbow SET CO
      oximeter (Masimo, Irvine, CA, USA). Immediately following induction of
      anesthesia, a blood sample for laboratory measurement of carboxyhemoglobin (COHb)
      and serum cotinine was obtained. Regression analysis determined the correlation
      of SpCO with serum cotinine values. Receiver operator characteristic (ROC) curves
      analyzed the discriminating ability of SpCO or COHb to predict ETS exposure based
      on cotinine cutoff values known to be present in children exposed to ETS.
      Agreement of SpCO and COHb values was assessed using Bland-Altman plots. RESULTS:
      SpCO did not correlate with cotinine (R(2) = 0.005). Both SpCO and COHb had poor
      discriminating ability for ETS exposure (area under the ROC curve = 0.606 and
      0.562, respectively). SpCO values had poor agreement with COHb values.
      CONCLUSIONS: The point-of-care multiple wavelength pulse CO-oximeter does not
      appear to be a useful preoperative screening tool for ETS exposure in children.

PMID- 22587735
TI  - Combination therapy in type 2 diabetes mellitus: adding linagliptin to a stable
      regimen of metformin and a sulfonylurea.
AB  - Linagliptin, the most recently approved drug of the dipeptidyl peptidase-4 (DPP
      4) inhibitor class, is an oral agent used to improve glycemic control in type 2
      diabetes mellitus (T2DM). By inhibiting the DPP-4 enzyme, these drugs slow the
      inactivation of the endogenous incretin hormones glucagon-like peptide-1 (GLP-1)
      and glucose-dependent insulinotropic polypeptide (GIP), in turn reducing blood
      glucose levels in a glucose-dependent manner. As well as significantly reducing
      glycosylated hemoglobin, the class has a good safety profile, with a low
      incidence of hypoglycemia, and is not associated with weight gain. From a
      practical point of view, they also have simple regimens, generally with once
      daily oral administration, and can be used as monotherapy or in combination with
      other anti-diabetic drugs. Owens and colleagues have reported a 6-month study of
      linagliptin add-on therapy in patients who were receiving a stable regimen of
      metformin and a sulfonylurea, but needed additional glycemic control. Linagliptin
      was associated with significant improvement in glycemic control and was well
      tolerated by patients, indicating that it provides a valuable option for a large
      number of patients with T2DM, especially for those who would prefer to add an
      oral therapy to a current regimen.

PMID- 22587736
TI  - Intraclass reliability for assessing how well Taiwan constrained hospital
      provided medical services using statistical process control chart techniques.
AB  - BACKGROUND: Few studies discuss the indicators used to assess the effect on cost
      containment in healthcare across hospitals in a single-payer national healthcare
      system with constrained medical resources. We present the intraclass correlation
      coefficient (ICC) to assess how well Taiwan constrained hospital-provided medical
      services in such a system. METHODS: A custom Excel-VBA routine to record the
      distances of standard deviations (SDs) from the central line (the mean over the
      previous 12 months) of a control chart was used to construct and scale annual
      medical expenditures sequentially from 2000 to 2009 for 421 hospitals in Taiwan
      to generate the ICC. The ICC was then used to evaluate Taiwan's year-based
      convergent power to remain unchanged in hospital-provided constrained medical
      services. A bubble chart of SDs for a specific month was generated to present the
      effects of using control charts in a national healthcare system. RESULTS: ICCs
      were generated for Taiwan's year-based convergent power to constrain its medical
      services from 2000 to 2009. All hospital groups showed a gradually well
      controlled supply of services that decreased from 0.772 to 0.415. The bubble
      chart identified outlier hospitals that required investigation of possible
      excessive reimbursements in a specific time period. CONCLUSION: We recommend
      using the ICC to annually assess a nation's year-based convergent power to
      constrain medical services across hospitals. Using sequential control charts to
      regularly monitor hospital reimbursements is required to achieve financial
      control in a single-payer nationwide healthcare system.

PMID- 22587737
TI  - Rape disclosure: the interplay of gender, culture and kinship in contemporary
      Vietnam.
AB  - This paper examines the social management of rape within kin groups in
      contemporary Vietnam, with a particular focus on the decision whether or not to
      seek legal redress. Post-rape management entails negotiations among families on
      matters such as apology and compensation before a decision is made about whether
      to report the incident to the authorities. By drawing on an ethnographic study of
      a limited number of respondents, this paper highlights how rape disclosure is
      often bound up with notions of family honour, with assumptions about kinship,
      gender relations, social belonging and shared responsibility in a collective
      society such as Vietnam.

PMID- 22587738
TI  - PerPlot & PerScan: tools for analysis of DNA curvature-related periodicity in
      genomic nucleotide sequences.
AB  - BACKGROUND: Periodic spacing of short adenine or thymine runs phased with DNA
      helical period of ~10.5 bp is associated with intrinsic DNA curvature and
      deformability, which play important roles in DNA-protein interactions and in the
      organization of chromosomes in both eukaryotes and prokaryotes. Local differences
      in DNA sequence periodicity have been linked to differences in gene expression in
      some organisms. Despite the significance of these periodic patterns, there are
      virtually no publicly accessible tools for their analysis. RESULTS: We present
      novel tools suitable for assessments of DNA curvature-related sequence
      periodicity in nucleotide sequences at the genome scale. Utility of the present
      software is demonstrated on a comparison of sequence periodicities in the genomes
      of Haemophilus influenzae, Methanocaldococcus jannaschii, Saccharomyces
      cerevisiae, and Arabidopsis thaliana. The software can be accessed through a web
      interface and the programs are also available for download. CONCLUSIONS: The
      present software is suitable for comparing DNA curvature-related sequence
      periodicity among different genomes as well as for analysis of intrachromosomal
      heterogeneity of the sequence periodicity. It provides a quick and convenient way
      to detect anomalous regions of chromosomes that could have unusual structural and
      functional properties and/or distinct evolutionary history.

PMID- 22587739
TI  - Fatigued patients with multiple sclerosis can be discriminated from healthy
      controls by the recordings of a newly developed measurement system (FAMOS): a
      pilot study.
AB  - PURPOSE: To explore the difference between fatigued patients with multiple
      sclerosis (MS) and matched healthy controls by applying a newly developed
      physiological and functional data recording system. METHODS: A portable wireless
      measurement system, named FAtigue MOnitoring System (FAMOS), has been developed,
      which can continuously measure electrocardiogram (ECG), body skin temperature,
      electromyogram, and motion parameters. In a pilot study, 17 fatigued MS patients
      (fatigue severity scale (FSS) = 53.9 SD 5.4) and 9 healthy matched controls (FSS
      = 27.2 SD 6.8) were recruited and monitored by FAMOS during the execution of
      functional (36 m walk test, 5- and 50-repetition sit-to-stand test) and cognitive
      (short-term memory tests) tests. Furthermore, oxygen saturation (SPO(2)) was
      measured during the functional and cognitive tests and during rest periods
      between these tests. RESULTS: Recordings from FAMOS indicate that fatigued MS
      patients have reduced standard deviation (SD) of the heart rate (HR) during the
      short-term memory test, reduced high frequency (HF) component power spectrum
      (representing parasympathetic activation) at rest after walk test, and higher
      ratio of low frequency (LF) to HF (LF/HF) during 50-repetition sit-to-stand test.
      CONCLUSIONS: FAMOS recordings can discriminate fatigued MS patients from healthy
      controls. The data indicate that fatigued MS patients have vagus nerve
      dysfunction during cognitive tests and disturbed sympathovagal balance during
      stressful physical tests. [Box: see text].

PMID- 22587741
TI  - Palladium-catalyzed synthesis of 2,3-disubstituted 5-azaindoles via
      heteroannulation reaction and of 2-substituted 5-azaindoles through domino sila
      Sonogashira/5-endo cyclization.
AB  - A general and efficient procedure for the synthesis of 2,3-disubstituted 5
      azaindoles through the palladium-catalyzed heteroannulation of 4-acetamido-3
      iodopyridines and diaryl-, dialkyl-, or arylalkylalkynes is described along with
      a study of the reaction regioselectivity. The preparation of 2-monosubstituted 5
      azaindoles via sila-Sonogashira/5-endo cyclization is also reported. These
      methods allowed us to prepare 36 diversely substituted 5-azaindoles in good
      yields.

PMID- 22587740
TI  - Inequity in maternal health care utilization in Vietnam.
AB  - INTRODUCTION: Vietnam has succeeded in reducing maternal mortality in the last
      decades. Analysis of survey data however indicate that large inequities exist
      between different segments of the population. We have analyzed utilization of
      antenatal care and skilled birth attendance among Vietnamese women of
      reproductive age in relation to social determinants with the aim to reveal health
      inequities and identify disadvantaged groups. METHOD: Data on maternal health
      care utilization and social determinants were derived from the Multiple Indicator
      Cluster Survey (MICS) conducted in Vietnam in 2006, and analyzed through
      stratified logistic regressions and g-computation. RESULTS: Inequities in
      maternal health care utilization persist in Vietnam. Ethnicity, household wealth
      and education were all significantly associated with antenatal care coverage and
      skilled birth attendance, individually and in synergy. Although the structural
      determinants included in this study were closely related to each other, analysis
      revealed a significant effect of ethnicity over and above wealth and education.
      Within the group of mothers from poor households ethnic minority mothers were at
      a three-fold risk of not attending any antenatal care (OR 3.06, 95% CI 1.27-7.41)
      and six times more likely not to deliver with skilled birth attendance (OR 6.27,
      95% CI 2.37-16.6). The association between ethnicity and lack of antenatal care
      and skilled birth attendance was even stronger within the non-poor group.
      CONCLUSIONS: In spite of policies to out rule health inequities, ethnic minority
      women constitute a disadvantaged group in Vietnam. More efficient ways to target
      disadvantaged groups, taking synergy effects between multiple social determinants
      into consideration, are needed in order to assure safe motherhood for all.

PMID- 22587742
TI  - Body mass index and 25 hydroxyvitamin D status in patients with and without heart
      failure.
AB  - The purpose of this pilot study was to assess the association between 25
      hydroxyvitamin D (25[OH]D) concentrations, vitamin D intake, and sunlight
      exposure in patients with heart failure (HF) compared with healthy volunteers.
      Fourteen healthy volunteers 50 and older were recruited to compare with 14
      patients with HF. Healthy volunteers were compared with HF patients by serum
      25(OH)D concentrations, dietary vitamin D intake, weekly sunlight exposure, and
      other covariates. Independent sample t tests and linear regression models were
      used to compare differences between healthy volunteers and patients with HF. The
      mean serum 25(OH)D concentration was not significantly different between groups
      (healthy volunteers 25.7 +/- 11.1 ng/mL, patients with HF 20.4 +/- 10.2 ng/mL;
      P=.2) and no group effect was found in any multivariable models. Body mass index
      regardless of group was found to be inversely associated with serum 25(OH)D
      concentrations (P=.025). There was no difference in the dietary intake of vitamin
      D or calcium between groups. The healthy volunteers had a significantly greater
      amount of sunlight exposure but this did not result in higher 25(OH)D when
      compared with those with HF. Our findings suggest that body mass index has an
      important relationship with 25(OH)D concentrations regardless of a person being
      healthy or having HF.

PMID- 22587743
TI  - Hyperuricemia and the echocardiographic measures of myocardial dysfunction.
AB  - Few studies have investigated the association between hyperuricemia and
      subclinical myocardial dysfunction. The authors analyzed the relationship between
      serum uric acid and subclinical markers of heart failure in participants in the
      Framingham Offspring Cohort (N=2169, mean age 57.3 years, 55.4% women). Cardiac
      dysfunction was assessed through echocardiographic measurements of left
      ventricular (LV) mass and thickness, end-diastolic LV thickness, and LV
      fractional shortening at the sixth visit, approximately 24 years after study
      onset. Participants in the highest serum uric acid quartile (>= 6.2 mg/dL serum
      uric acid) had a significantly greater frequency of echocardiographic
      abnormalities compared with those in the lowest quartile (<4.3 mg/dL). Those in
      the highest quartile had multivariable-adjusted odds ratios of 9.013 (95%
      confidence interval, 2.051-39.604) for abnormal LV ejection fraction and 4.584
      (95% confidence interval, 1.951-10.768) for LV systolic dysfunction compared with
      those in the lowest quartile. Hyperuricemia in young adults can be a marker for
      subsequent heart failure.

PMID- 22587744
TI  - Serum carbohydrate antigen 125 levels in nonischemic dilated cardiomyopathy: a
      useful biomarker for prognosis and functional mitral regurgitation.
AB  - The authors investigated the prognostic relevance of serum carbohydrate antigen
      125 (CA125) levels in nonischemic dilated cardiomyopathy (NICMP) and assessed
      whether increased levels relate to the degree of functional mitral regurgitation
      (FMR). Seventy-seven patients with NICMP were enrolled and followed-up for 10 +/-
      2 months in this prospective study. Receiver-operating characteristic analysis
      established a cutoff CA125 value of 25 U/mL for predicting mortality. Patients
      were divided into two groups according to their CA125 levels (CA125 <25 U/mL
      [n=58] and CA125 >= 25 U/mL [n=19]). Patients with high CA125 values had
      statistically worse functional status, higher B-type natriuretic peptide (BNP)
      levels, higher left ventricular volumes, lower ejection fraction, higher E/Em
      ratio, higher pulmonary artery systolic pressure, and more severe FMR. On the
      multivariate analysis, serum CA125 (P=.002) and severe FMR (P=.04) were
      identified as the independent predictors of mortality. Serum CA125 levels also
      correlated with BNP levels and FMR severity (P<.001). Serum CA125 is a powerful
      prognostic biomarker that is associated with the severity of heart failure, serum
      BNP levels and several echocardiographic parameters including left ventricular
      volumes, systolic and diastolic functions, pulmonary artery pressure, and the
      degree of FMR. Serum CA125 was also shown as an independent predictor of
      mortality during 10 +/- 2 months of follow-up.

PMID- 22587745
TI  - Worsening renal function and prognosis in pulmonary hypertension patients
      hospitalized for right heart failure.
AB  - Increased central venous pressures have been associated with the development of
      worsening renal function (WRF), an important marker of prognosis. We sought to
      determine the incidence and prognostic significance of WRF in pulmonary
      hypertension patients (PH) with isolated right HF. A prospective study of PH
      clinic patients admitted to hospital for right HF. WRF was defined as a rise in
      creatinine of 26 MUmol/L (0.3 mg/dL) within the first 48 hours of admission. A
      total of 32 patients were enrolled in this study, 67% of patients had moderate
      severe chronic kidney disease with an eGFR <= 60 mL/min and 34% (n=11) developed
      WRF during their admission. The mean right atrial pressure was higher in patients
      with WRF (19 +/- 7 mm Hg vs 12 +/- 6 mm Hg, P=.05). A total of 36% of patients
      with WRF died in hospital compared to 5% in the group that did not develop WRF
      (OR for hospital death 13.3 +/- 16, P=.03). The combined endpoint of death or
      readmission at 6 months was 45% in the WRF group and 43% in the group without WRF
      (P=.89). Significant renal dysfunction is common in patients with PH and an acute
      decline in renal function is an important marker of in hospital death and short
      term mortality in right heart failure.

PMID- 22587746
TI  - Poor prognosis in chronic heart failure patients with reduced ejection fraction
      in China.
AB  - Most Chinese cardiologists are challenged by the high mortality rate of heart
      failure (HF) in patients with reduced ejection fraction in China. This study was
      designed as a single-center, retrospective study. All consecutive HF patients
      with left ventricular ejection fraction (LVEF) <= 45% from January 1, 2007, to
      December 31, 2009, were enrolled. The primary outcome was all-cause mortality.
      The secondary outcome was all-cause mortality or the first cardiovascular
      readmission event. A total of 187 patients comprised the study population,
      classified into two groups: LVEF <= 35% (n=83) and LVEF 36% to 45% (n=104). The
      median follow-up was 18 months (2-41 months). All-cause mortality was 27% among
      patients with LVEF <= 35%, as compared with 14% among those with LVEF 36% to 45%
      (P=.025). All-cause mortality or first cardiovascular readmission rates were 53%
      and 32% among patients with LVEF <= 35% and 36% to 45% (P=.003), respectively.
      The predictors of all-cause mortality were advanced age and New York Heart
      Association functional class, chronic kidney disease, oral beta-blockers, and
      statins at discharge. The prognosis of chronic HF patients with LVEF <= 45% was
      poor in China, especially for patients with LVEF <= 35%. Cardiologists should
      provide further efforts to improve the prognosis of HF in Chinese patients.

PMID- 22587747
TI  - Review of ambulatory pulmonary artery catheterization in the management of
      advanced heart failure.
AB  - The use of pulmonary artery catheterization (PAC) has declined secondary to
      associated complications and lack of demonstrable efficacy in the inpatient
      setting. Few studies have been published on the use of PAC in nonacute heart
      failure (HF) patients. The purpose of this study was to review the use of PAC in
      guiding advanced therapy in nonacute ambulatory HF patients. A retrospective
      observational study assessing our group's practice pattern with regard to the use
      of PAC in 515 ambulatory HF patients, outcomes, and adverse events that resulted
      from its use was performed. A total of 159 ambulatory HF patients were referred
      for PAC; 7% underwent heart transplant, 6% had ventricular assist device (VAD)
      placement, 18% underwent inotropic therapy, and 48% had addition of therapy while
      14% had subtraction of therapy. Adverse events occurred in 4% of ambulatory PAC.
      Patients who underwent heart transplant, VAD, or inotropic therapy had
      significantly elevated pulmonary capillary wedge pressures, mean pulmonary artery
      pressures, and depressed cardiac index. Patients selected for inotropic therapy
      also had significantly elevated right atrial pressures and depressed ejection
      fractions. PAC use safely guided medical therapy in more than half of the
      nonacute ambulatory patients.

PMID- 22587748
TI  - Uric acid, heart failure survival, and the impact of xanthine oxidase inhibition.
AB  - Increasing evidence suggests that serum uric acid (UA), a product of xanthine
      oxidase (XO), may be a useful marker for metabolic, hemodynamic, and functional
      staging in heart failure (HF) and a valid predictor of survival in HF patients.
      Recent data support an expanded role for UA and the XO pathway in the
      pathogenesis of HF, as studies have shown that an elevation in the enzymatic
      activity of XO can lead to increases in oxidative stress, endothelial
      dysfunction, and reduced myocardial function. Numerous population studies have
      previously reported that elevated UA levels are an independent predictor of
      cardiovascular mortality, and recent evidence suggests that lowering serum levels
      of UA may lead to improved outcomes in HF patients. The question of whether UA is
      only a marker rather than a causal factor in the pathogenesis of HF remains.
      Regardless of whether UA levels are ready for routine clinical use, either as a
      prognostic factor or novel therapeutic target, further prospective studies are
      necessary to demonstrate that routine measurement or reduction of UA levels
      improves outcomes in HF patients.

PMID- 22587749
TI  - Severe dilated cardiomyopathy in a patient with myotonic dystrophy type 2 and
      homozygous repeat expansion in ZNF9.

PMID- 22587750
TI  - Fungicide-induced declines of freshwater biodiversity modify ecosystem functions
      and services.
AB  - Although studies on biodiversity and ecosystem function are often framed within
      the context of anthropogenic change, a central question that remains is how
      important are direct vs. indirect (via changes in biodiversity) effects of
      anthropogenic stressors on ecosystem functions in multitrophic-level communities.
      Here, we quantify the effects of the fungicide chlorothalonil on 34 species-, 2
      community- and 11 ecosystem-level responses in a multitrophic-level system. At
      ecologically relevant concentrations, chlorothalonil increased mortality of
      amphibians, gastropods, zooplankton, algae and a macrophyte (reducing taxonomic
      richness), reduced decomposition and water clarity and elevated dissolved oxygen
      and net primary productivity. These ecosystem effects were indirect and
      predictable based on changes in taxonomic richness. A path analysis suggests that
      chlorothalonil-induced reductions in biodiversity and top-down and bottom-up
      effects facilitated algal blooms that shifted ecosystem functions. This work
      emphasises the need to re-evaluate the safety of chlorothalonil and to further
      link anthropogenic-induced changes in biodiversity to altered ecosystem
      functions.

PMID- 22587752
TI  - Bone health in persons with haemophilia: a review.
AB  - Bone density is a measure of equilibrium between bone formation and bone
      resorption; any imbalance in these two processes might lead to osteopenia and
      osteoporosis. Osteoporosis in general has been considered to be an important
      cause of morbidity in both men and women and more so in haemophilia and other
      bleeding disorders. Specific triggering factors in persons with haemophilia (PWH)
      are abnormal liver function because of viral infection, bleeding and
      inflammation, lack of physical and athletic activities, low body weight and
      others. Although the pathogenesis of osteoporosis is not clear, it has been
      considered as a severe comorbidity in PWH in both developing and developed
      countries. This is more evident in developing countries where there is no free
      access to factor concentrates, and primary prophylaxis is beyond the reach of
      vast majority of the patients. Only few references are available in the
      literature on the prevalence and management of osteoporosis in haemophilia
      population. This review summarises the prevalence, plausible mechanisms and
      management options of this important morbidity in PWH.

PMID- 22587753
TI  - Stereoselective intermolecular allylic C-H trifluoroacetoxylation of
      functionalized alkenes.
AB  - Pd-catalyzed allylic C-H trifluoroacetoxylation of substituted alkenes was
      performed using PhI(OCOCF(3))(2) as the oxidant and acyloxy source.
      Trifluoroacetoxylation of monosubstituted cyclopentenes and cyclohexenes proceeds
      with excellent regio- and diastereoselectivity. Studies with one of the possible
      (eta(3)-allyl)Pd(II) intermediates suggest that the reaction proceeds via
      stereoselective formation of Pd(IV) intermediates and subsequent stereo- and
      regioselective reductive elimination of the product.

PMID- 22587751
TI  - Resiliency in adolescents at high risk for substance abuse: flexible adaptation
      via subthalamic nucleus and linkage to drinking and drug use in early adulthood.
AB  - INTRODUCTION: The personality trait resiliency is the ability to flexibly adapt
      impulse control relative to contextual demand. Low resiliency has been linked to
      later alcohol/drug problems. The underlying psychological and neural mechanisms
      are unknown, but neurocomputational models suggested relations between resiliency
      and working memory. Cortical-striatal connectivity has been proposed to underlie
      adaptive switches between cautious and risky behaviors. METHODS: Working memory
      was probed in sixty-seven 18- to 22-year-olds from a larger community study of
      alcoholism, using the n-back task during functional magnetic resonance imaging.
      Functional connectivity between task-related regions was investigated with
      psychophysiological interaction analysis. Resiliency was measured in early teen
      years and related to early adulthood measures of drinking/drug use, task
      activation, and connectivity. Relationships with risk factors, including family
      history, age of drinking onset, and number of alcohol problems, were also
      investigated. RESULTS: Higher resiliency was related to lower levels of substance
      use, fewer alcohol problems, and better working memory performance. Whole-brain
      regression revealed resiliency negatively correlated with activation of
      subthalamic nucleus (STN) and pallidum during the n-back. High and Low resiliency
      quartile groups (n = 17 each) differed in coupling strength between STN and
      median cingulate cortex, a region of reduced activation during working memory.
      The high resiliency group had later onset of drinking, fewer alcohol problems,
      had used fewer illicit drugs, and were less likely to smoke cigarettes than their
      low resiliency counterparts. CONCLUSIONS: These findings suggest that resiliency
      in early adolescence may protect against alcohol problems and drug use, although
      the direction of this effect is currently unknown. This protective factor may
      relate to executive functioning as supported by the finding of a neural link
      shared between resiliency and working memory in basal ganglia structures. The
      STN, a key basal ganglia structure, may adaptively link flexible impulse control
      with cognitive processing, potentially modulating substance use outcomes.

PMID- 22587754
TI  - Base-By-Base version 2: single nucleotide-level analysis of whole viral genome
      alignments.
AB  - BACKGROUND: Base-By-Base is a Java-based multiple sequence alignment editor. It
      is capable of working with protein and DNA molecules, but many of its unique
      features relate to the manipulation of the genomes of large DNA viruses such as
      poxviruses, herpesviruses, baculoviruses and asfarviruses (1-400 kb). The tool
      was built to serve as a platform for comparative genomics at the level of
      individual nucleotides. RESULTS: In version 2, BBB-v2, of Base-By-Base we have
      added a series of new features aimed at providing the bench virologist with a
      better platform to view, annotate and analyze these complex genomes. Although a
      poxvirus genome, for example, may be less than 200 kb, it probably encodes close
      to 200 proteins using multiple classes of promoters with frequent overlapping of
      promoters and coding sequences and even some overlapping of genes. The new
      features allow users to 1) add primer annotations or other data sets in batch
      mode, 2) export differences between sequences to other genome browsers, 3)
      compare multiple genomes at a single nucleotide level of detail, 4) create new
      alignments from subsets/subsequences of a very large master alignment and 5)
      allow display of summaries of deep RNA sequencing data sets on a genome sequence.
      CONCLUSION: BBB-v2 significantly improves the ability of virologists to work with
      genome sequences and provides a platform with which they can use a multiple
      sequence alignment as the basis for their own editable documents. Also, a .bbb
      document, with a variety of annotations in addition to the basic coding regions,
      can be shared among collaborators or made available to an entire research
      community. The program is available via Virology.ca using Java Web Start and is
      platform independent; the Java 1.5 virtual machine is required.

PMID- 22587756
TI  - Stakeholders' perspective on ecological modeling in environmental risk assessment
      of pesticides: challenges and opportunities.
AB  - The article closely examines the role of mechanistic effect models (e.g.,
      population models) in the European environmental risk assessment (ERA) of
      pesticides. We studied perspectives of three stakeholder groups on population
      modeling in ERA of pesticides. Forty-three in-depth, semi-structured interviews
      were conducted with stakeholders from regulatory authorities, industry, and
      academia all over Europe. The key informant approach was employed in recruiting
      our participants. They were first identified as key stakeholders in the field and
      then sampled by means of a purposive sampling, where each stakeholder identified
      as important by others was interviewed and asked to suggest another potential
      participant for our study. Our results show that participants, although having
      different institutional backgrounds often presented similar perspectives and
      concerns about modeling. Analysis of repeating ideas and keywords revealed that
      all stakeholders had very high and often contradicting expectations from models.
      Still, all three groups expected effect models to become integrated in future ERA
      of pesticides. Main hopes associated with effect models were to reduce the amount
      of expensive and complex testing and field monitoring, both at the product
      development stage, and as an aid to develop mitigation measures. Our analysis
      suggests that, although the needs of stakeholders often overlapped, subtle
      differences and lack of trust hinder the process of introducing mechanistic
      effect models into ERA.

PMID- 22587755
TI  - Pharmacogenetically driven treatments for alcoholism: are we there yet?
AB  - Pharmacogenetic analyses of treatments for alcohol dependence attempt to predict
      treatment response and side-effect risk for specific medications. We review the
      literature on pharmacogenetics relevant to alcohol dependence treatment, and
      describe state-of-the-art methods of pharmacogenetic research in this area. Two
      main pharmacogenetic study designs predominate: challenge studies and treatment
      trial analyses. Medications studied include US FDA-approved naltrexone and
      acamprosate, both indicated for treating alcohol dependence, as well as several
      investigational (and off-label) treatments such as sertraline, olanzapine and
      ondansetron. The best-studied functional genetic variant relevant to alcoholism
      treatment is rs1799971, a single-nucleotide polymorphism in exon 1 of the OPRM1
      gene that encodes the MU-opioid receptor. Evidence from clinical trials suggests
      that the presence of the variant G allele of rs1799971 may predict better
      treatment response to opioid receptor antagonists such as naltrexone. Evidence
      from clinical trials also suggests that several medications interact
      pharmacogenetically with variation in genes that encode proteins involved in
      dopaminergic and serotonergic neurotransmission. Variation in the DRD4 gene,
      which encodes the dopamine D(4) receptor, may predict better response to
      naltrexone and olanzapine. A polymorphism in the serotonin transporter gene
      SLC6A4 promoter region appears related to differential treatment response to
      sertraline depending on the subject's age of onset of alcoholism. Genetic
      variation in SLC6A4 may also be associated with better treatment response to
      ondansetron. Initial pharmacogenetic efforts in alcohol research have identified
      functional variants with potential clinical utility, but more research is needed
      to further elucidate the mechanism of these pharmacogenetic interactions and
      their moderators in order to translate them into clinical practice.

PMID- 22587757
TI  - Bendability optimization of flexible optical nanoelectronics via neutral axis
      engineering.
AB  - The enhancement of bendability of flexible nanoelectronics is critically
      important to realize future portable and wearable nanoelectronics for personal
      and military purposes. Because there is an enormous variety of materials and
      structures that are used for flexible nanoelectronic devices, a governing design
      rule for optimizing the bendability of these nanodevices is required. In this
      article, we suggest a design rule to optimize the bendability of flexible
      nanoelectronics through neutral axis (NA) engineering. In flexible optical
      nanoelectronics, transparent electrodes such as indium tin oxide (ITO) are
      usually the most fragile under an external load because of their brittleness.
      Therefore, we representatively focus on the bendability of ITO which has been
      widely used as transparent electrodes, and the NA is controlled by employing a
      buffer layer on the ITO layer. First, we independently investigate the effect of
      the thickness and elastic modulus of a buffer layer on the bendability of an ITO
      film. Then, we develop a design rule for the bendability optimization of flexible
      optical nanoelectronics. Because NA is determined by considering both the
      thickness and elastic modulus of a buffer layer, the design rule is conceived to
      be applicable regardless of the material and thickness that are used for the
      buffer layer. Finally, our design rule is applied to optimize the bendability of
      an organic solar cell, which allows the bending radius to reach about 1 mm. Our
      design rule is thus expected to provide a great strategy to enhance the bending
      performance of a variety of flexible nanoelectronics.

PMID- 22587759
TI  - Measurement of volatile organic compounds emitted in libraries and archives: an
      inferential indicator of paper decay?
AB  - BACKGROUND: A sampling campaign of indoor air was conducted to assess the typical
      concentration of indoor air pollutants in 8 National Libraries and Archives
      across the U.K. and Ireland. At each site, two locations were chosen that
      contained various objects in the collection (paper, parchment, microfilm,
      photographic material etc.) and one location was chosen to act as a sampling
      reference location (placed in a corridor or entrance hallway). RESULTS: Of the
      locations surveyed, no measurable levels of sulfur dioxide were detected and low
      formaldehyde vapour (< 18 MUg m-3) was measured throughout. Acetic and formic
      acids were measured in all locations with, for the most part, higher acetic acid
      levels in areas with objects compared to reference locations. A large variety of
      volatile organic compounds (VOCs) was measured in all locations, in variable
      concentrations, however furfural was the only VOC to be identified consistently
      at higher concentration in locations with paper-based collections, compared to
      those locations without objects. To cross-reference the sampling data with VOCs
      emitted directly from books, further studies were conducted to assess emissions
      from paper using solid phase microextraction (SPME) fibres and a newly developed
      method of analysis; collection of VOCs onto a polydimethylsiloxane (PDMS)
      elastomer strip. CONCLUSIONS: In this study acetic acid and furfural levels were
      consistently higher in concentration when measured in locations which contained
      paper-based items. It is therefore suggested that both acetic acid and furfural
      (possibly also trimethylbenzenes, ethyltoluene, decane and camphor) may be
      present in the indoor atmosphere as a result of cellulose degradation and
      together may act as an inferential non-invasive marker for the deterioration of
      paper. Direct VOC sampling was successfully achieved using SPME fibres and
      analytes found in the indoor air were also identified as emissive by-products
      from paper. Finally a new non-invasive, method of VOC collection using PDMS
      strips was shown to be an effective, economical and efficient way of examining
      VOC emissions directly from the pages of a book and confirmed that toluene,
      furfural, benzaldehyde, ethylhexanol, nonanal and decanal were the most
      concentrated VOCs emitted directly from paper measured in this study.

PMID- 22587760
TI  - QSAR and computer aided drug design.

PMID- 22587761
TI  - Fullerene derivative as anti-HIV protease inhibitor: molecular modeling and QSAR
      approaches.
AB  - A Fullerene based system is modified in order to increase its solubility and
      enhance its ability to carry a protein-like structure. The modified structure,
      which is proposed to act as HIV-1 protease inhibitor, is [C60-C2H4N-(2,4-
      XCOCH2OH)C6H4], where the X atom is either O, S or Se. The geometry optimization,
      vibrational spectra and thermodynamics were performed using semiempirical quantum
      mechanical PM3 method in order to study the proposed compounds. Furthermore, the
      quantitative structure activity relationship (QSAR) properties of the compounds
      are calculated at the same level of theory. Results indicate a possible use of
      the investigated structures as HIV-1 protease inhibitors. The compounds
      containing oxygen is more stable as compared to the other two compounds.

PMID- 22587762
TI  - Review of theoretical studies for prediction of neurodegenerative inhibitors.
AB  - Alzheimer's disease (AD) is characterized by several pathologies, this disease is
      a neuropathological lesion in brain. Indeed, a wealth of evidence suggests that
      beta-amyloid is central to the pathophysiology of AD and is likely to play an
      early role in this intractable neurodegenerative disorder. AD is the most
      prevalent form of dementia, and current indications show that twenty-nine million
      people live with AD worldwide, a figure expected rise exponentially over the
      coming decades. Clearly, blocking disease progression or, in the best-case
      scenario, preventing AD altogether would be of benefit in both social and
      economic terms. However, current AD therapies are merely palliative and only
      temporarily slow cognitive decline, and treatments that address the underlying
      pathologic mechanisms of AD are completely lacking. While familial AD (FAD) is
      caused by autosomal dominant mutations in either amyloid precursor protein (APP)
      or the presenilin (PS1, PS2) genes. First, we revised 2D QSAR, 3D QSAR, CoMFA,
      CoMSIA and Docking of beta and gamma-secretase inhibitors. Next, we review 2D
      QSAR, 3D QSAR, CoMFA, CoMSIA and docking for GSK-3alpha and GSK-3beta with
      different compound to find out the structural requirements.

PMID- 22587763
TI  - Evaluation of the pharmacological descriptors related to the induction of
      antidepressant activity and its prediction by QSAR/QRAR methods.
AB  - Antidepressants are psychiatric agents used for the treatment of different types
      of depression, being at present amongst the most commonly prescribed drugs, while
      their effectiveness and adverse effects are still the subject of many studies. To
      reduce the inefficiency of known antidepressants caused by their side-effects,
      many research efforts have recently focused on the development of improved
      strategies for new antidepressants drug design. For this reason it is necessary
      to apply very fast and precise techniques, such as QSAR (Quantitative Structure
      Activity Relationships) and QRAR (Quantitative Retention-Activity Relationship),
      which are capable to analyze and predict the biological activity for these
      structures, taking in account the possible changes of the molecular structures
      and chromatographic parameters. We discuss the pharmaceutical descriptors (van
      der Waals, electrostatic, hydrophobicity, hydrogen donor/acceptor bond, Verloop's
      parameters, polar area) involved in QSAR and also chromatographic parameters
      involved in QRAR studies of antidepressants. Antidepressant activities of alkanol
      piperazine, acetamides, arylpiperazines, thienopyrimidinone derivatives (as
      preclinical antidepressants) and also the antidepressants already used in
      clinical practice are mentioned.

PMID- 22587764
TI  - On the use of the metric rm2 as an effective tool for validation of QSAR models
      in computational drug design and predictive toxicology.
AB  - Validation of quantitative structure-activity relationship (QSAR) models plays a
      key role for the selection of robust and predictive models that may be employed
      for further activity prediction of new molecules. Traditionally, QSAR models are
      validated based on classical metrics for internal (Q2) and external validation
      (R2 pred). Recently, it has been shown that for data sets with wide range of the
      response variable, these traditional metrics tend to achieve high values without
      truly reflecting absolute differences between the observed and predicted response
      values, as in both cases the reference for comparison of the predicted residuals
      is the deviations of the observed values from the training set mean. Roy et al.
      have recently developed a new parameter, modified r2 (rm2), which considers the
      actual difference between the observed and predicted response data without
      consideration of training set mean thereby serving as a more stringent measure
      for assessment of model predictivity compared to the traditional validation
      parameters (Q2 and R2 pred). The rm2 parameter has three different variants: (i)
      rm2 (LOO) for internal validation, (ii) rm2 (test) for external validation and
      (iii) rm2 (overall) for analyzing the overall performance of the developed model
      considering predictions for both internal and external validation sets. Thus, the
      rm2 metrics strictly judge the ability of a QSAR model to predict the
      activity/toxicity of untested molecules. The present review provides a survey of
      the development of different rm2 metrics followed by their applications in
      modeling studies for selection of the best QSAR models in different reports made
      by several workers.

PMID- 22587765
TI  - Quantitative structure-activity relationship (QSAR) analysis to predict drug-drug
      interactions of ABC transporter ABCG2.
AB  - Quantitative structure-activity relationship (QSAR) analysis is a practical
      approach by which chemical structure is quantitatively correlated with biological
      activity or chemical reactivity. Human ABC transporter ABCG2 exhibits broad
      substrate specificity toward structurally diverse compounds. To gain insight into
      the relationship between the molecular structures of compounds and the
      interaction with ABCG2, we have developed an algorithm that analyzes QSAR to
      evaluate ABCG2-drug interactions. In addition, to support QSAR analysis, we
      developed a high-speed screening method for analyzing the drug-drug interactions
      of ABCG2. Based on both experimental results and computational QSAR analysis
      data, we propose a hypothetical mechanism underlying ABC-mediated drug transport
      and its interaction with drugs.

PMID- 22587766
TI  - Binding modes and pharmacophore modelling of thermolysin inhibitors.
AB  - In the present paper 25 known thermolysin inhibitors were docked into thermolysin
      using the Internal Coordinate Mechanics (ICM) software. Pharmacophore models
      based on thermolysin binding modes and activity profiles were generated using the
      LigandScout program. The docking studies indicated that all 25 inhibitors
      coordinated the catalytic zinc in bidentate or monodentate geometry. A 'three
      point' pharmacophore model was proposed which consisted of a hydrophobic group, a
      negative ionizable group and a hydrogen bond acceptor group. Finally the
      pharmacophore model has been tested against a small compound library containing
      18 highly, moderately, less active as well as inactive compounds. The screening
      indicated that the pharmacophore model could, identify highly active compounds in
      front of inactive or less active ones.

PMID- 22587767
TI  - QSPR in oral bioavailability: specificity or integrality?
AB  - During the last decade the technological advances in drug discovery changed the
      absorption, distribution, metabolism, excretion and toxicity (ADMET) profiles of
      New Chemical Entities (NCEs). Among ADMET processes, absorption plays an
      important role in the research and development of more effective orally
      administered drugs. Although significant progress has been made in in vitro, in
      situ and in vivo experimental determinations of absorption, the development of in
      silico methodologies has emerged as a cheaper and fast alternative to predict
      them. Even though several in silico models have been described in the literature
      to predict oral bioavailability and related properties, the prediction accuracy
      and their potential use is still limited. The low precision and high variability
      of data, the lack of a complete experimental and theoretical validation of in
      silico approach, and above all, the multi-factorial nature of the oral absorption
      term, make the development of predictive in silico models a thorny task. The
      present review discusses several important advances regarding the QSPR approaches
      used in the development of predictive oral bioavailability models. The importance
      of fixing the problem associated with data resource, as well as improving the
      reliability of in silico results is highlighted. Optimization of individual
      properties along the absorption process must be integrated in a multi-objective
      scenario for studying oral bioavailability behavior in the early drug discovery
      and development.

PMID- 22587768
TI  - Estimation of the binding free energy by Linear Interaction Energy models.
AB  - Since Hansch's extra thermodynamic multi-parameter approach, originally coined as
      Linear Free Energy Relationship, great efforts in medicinal chemistry have been
      made to properly estimate the binding free energy. Despite the often small
      amount, its value is however very critical in determining a successful binding.
      As a result, its correct estimation may provide a guide for a prospective
      rational drug design. The calculation of the absolute binding free energies is
      however a very challenging task as it requires a rigorous treatment of a number
      of physical terms that are both very time demanding and to some extent not
      immediately interpretable. In view of this, the introduction of some numerical
      approximations has permitted to develop the so called Linear Interaction Energy
      method that, at present, constitutes the best compromise among accuracy, speed of
      computation and easy interpretation. The initially developed Linear Interaction
      Energy method was subsequently revisited and several important improvements have
      been made. Significant examples are the Extended Linear Response, the surface
      generalized Born LIE, the molecular mechanics generalized Born surface area, the
      linear interaction energy in continuum electrostatics as well as its quantum
      mechanics variant. Principles and selected applications of these methods will be
      herein reviewed.

PMID- 22587769
TI  - A critical view on antimalarial endoperoxide QSAR studies.
AB  - Malaria is one of the most dangerous diseases in developing countries. The
      chemotherapy of malaria has been based on drugs developed more than half a
      century ago. These drugs are continuously losing their efficacy, mainly due to
      multi-drug resistance developed by the malaria-causing parasite. In the last
      three decades, artemisinin and artemisinin-like compounds have proven to be
      efficient alternatives to the chemotherapeutic control of malaria. These facts
      have led to an increasing interest in the development of Quantitative Structure
      Activity Relantioship (QSAR) models for these compounds. This work presents a
      critical view on some QSAR models, and shows that, due to lack of a rigorous
      selection of the descriptors entering the models, most of them are unable to
      accurately indicate the molecular cause of biological activity. Some reasons for
      the weakness of the published models are discussed.

PMID- 22587770
TI  - QSAR and QM/MM approaches applied to drug metabolism prediction.
AB  - In modern drug discovery process, ADME/Tox properties should be determined as
      early as possible in the test cascade to allow a timely assessment of their
      property profiles. To help medicinal chemists in designing new compounds with
      improved pharmacokinetics, the knowledge of the soft spot position or the site of
      metabolism (SOM) is needed. In recent years, large number of in silico approaches
      for metabolism prediction have been developed and reported. Among these methods,
      QSAR models and combined quantum mechanics/molecular mechanics (QM/MM) methods
      for predicting drug metabolism have undergone significant advances. This review
      provides a perspective of the utility of QSAR and QM/MM approaches on drug
      metabolism prediction, highlighting the present challenges, limitations, and
      future perspectives in medicinal chemistry.

PMID- 22587771
TI  - Discovery of anti-Alzheimer agents: current ligand-based approaches toward the
      design of acetylcholinesterase inhibitors.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by
      progressive dementia and loss of cognitive abilities. Until now, AD remains
      incurable. The principal biological target for AD therapy is acetylcholinesterase
      (AChE). Thus, the search for new drug candidates like AChE inhibitors constitutes
      an essential part for the discovery of more potent anti-AD agents. In general
      terms, rational drug design methodologies have played a decisive role. The
      present work is focused on the current state of the Ligand-Based Drug Design
      (LBDD) methods which have been applied to the elucidation of new molecular
      entities with high anti-AChE activity. Also, as a contribution to this field, we
      suggest a promising fragment-based approach for the search and prediction of new
      AChE inhibitors and for the fast and efficient extraction of substructural alerts
      which are responsible for the anti-AChE activity.

PMID- 22587772
TI  - Efficacy of first-line doxorubicin and ifosfamide in myxoid liposarcoma.
AB  - BACKGROUND: Myxoid liposarcoma (MLS) is a soft tissue sarcoma with adipocytic
      differentiation characterized by a unique chromosome rearrangement,
      t(12;16)(q13;p11). The exact efficacy of chemotherapy in MLS has not been clearly
      established. PATIENTS AND METHODS: We retrospectively analyzed the records of 37
      histologically confirmed MLS patients who were treated at the University of Texas
      MD Anderson Cancer Center from January 2000 to December 2009 with doxorubicin 75
      90 mg/m2 over 72 hours combined with ifosfamide 10 gm/m2 in the first-line
      setting. Response was assessed using RECIST and Choi criteria. The Kaplan-Meier
      method and log-rank test was used to estimate clinical outcomes. RESULTS: The
      median follow-up period was 50.1 months. The overall response rates were 43.2%
      using RECIST and 86.5% using the Choi criteria. The 5-year disease-free survival
      rate was 90% for patients with resectable tumors. Median time to progression and
      overall survival time for the advanced-disease group were 23 and 31.1 months,
      respectively. CONCLUSION: Our study demonstrates that doxorubicin-ifosfamide
      combination therapy has a role in the treatment of MLS. The Choi criteria may be
      more sensitive in evaluating response to chemotherapy in MLS.

PMID- 22587773
TI  - Increasing prevalence of ESBL production among Irish clinical Enterobacteriaceae
      from 2004 to 2008: an observational study.
AB  - BACKGROUND: Extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae
      infections are associated with delayed initiation of appropriate treatment, poor
      outcomes and increased hospital stay and expense. Although initially associated
      with healthcare settings, more recent international reports have shown increasing
      isolation of ESBLs in the community. Both hospital and community ESBL
      epidemiology in Ireland are poorly defined. METHODS: This report describes
      clinical and laboratory data from three hospitals over 4.5 years. All significant
      isolates of Enterobacteriaceae were subjected to standardized antimicrobial
      susceptibility testing and screening for ESBL production. Available patient data
      from hospital databases were reviewed. RESULTS: The database included 974 ESBL
      producing organisms from 464 patients. Urine and blood isolates represented 84%
      and 3% of isolates respectively. E. coli predominated (90.9%) followed by K.
      pneumoniae (5.6%). The majority of patients (n = 246, 53.0%) had been admitted to
      at least one of the study hospitals in the year prior to first isolation of ESBL.
      The overall 30-day all-cause mortality from the date of culture positivity was
      9.7% and the 1 year mortality was 61.4%. A Cox regression analysis showed age
      over 60, male gender and previous hospital admissions were significant risk
      factors for death within 30 days of ESBL isolation. Numbers of ESBL-producing E.
      coli isolated from urine and blood cultures increased during the study. Urine
      isolates were more susceptible than blood isolates. Co-resistance to other
      classes of antimicrobial agents was more common in ESBL producers from residents
      of long stay facilities (LSF) compared with hospital inpatients who lived at
      home. CONCLUSIONS: This work demonstrates a progressively increasing prevalence
      of ESBL Enterobacteriaceae in hospital, LSF and community specimens in a defined
      catchment area over a long time period . These results will improve clinician
      awareness of this problem and guide the development of empiric antimicrobial
      regimens for community acquired bloodstream and urinary tract infections.

PMID- 22587774
TI  - Hemodynamic changes during spinal anesthesia in premature infants with congenital
      heart disease undergoing inguinal hernia correction.
AB  - INTRODUCTION: There are conflicting reports on the effects of spinal anesthesia
      (SA) on hemodynamics. Data on the hemodynamic effects of SA in infants with
      congenital heart disease (CHD) are limited. METHODS: We reviewed our experience
      with 44 unsupplemented SA with 1 mg.kg(-1) of either hyperbaric tetracaine or
      bupivacaine in premature and former premature infants with noncyanotic CHD.
      Hemodynamics and oxyhemoglobin saturation (SpO(2)) were assessed. Neither
      preoperative fluid boluses nor atropine was administered to any of the infants.
      RESULTS: There was no significant change in systolic, diastolic, or mean blood
      pressures from pre-SA induction compared with end of surgery. Heart rate showed a
      small but systematic decline (mean change of 10 beats per minute, P < 0.01) but
      was within the normative range values for age. There was a small, but clinically
      insignificant increase in SpO(2) across the time course. Intraoperatively, two
      infants developed transient apneic spells. No infant developed postoperative
      apnea, oxygen desaturation, or bradycardia. CONCLUSIONS: The data suggest that SA
      with 1 mg.kg(-1) of either hyperbaric tetracaine or bupivacaine can be used
      safely as the sole anesthetic for inguinal hernia repair in infants with
      noncyanotic CHD even when fluid restricted and apparently causes minimal
      respiratory complications in these infants.

PMID- 22587775
TI  - Tackling inequalities in obesity: a protocol for a systematic review of the
      effectiveness of public health interventions at reducing socioeconomic
      inequalities in obesity amongst children.
AB  - BACKGROUND: There is growing evidence of the impact of overweight and obesity on
      short- and long-term functioning, health and well-being. Internationally,
      childhood obesity rates continue to rise in some countries (for example, Mexico,
      India, China and Canada), although there is emerging evidence of a slowing of
      this increase or a plateauing in some age groups. In most European countries, the
      United States and Australia, however, socioeconomic inequalities in relation to
      obesity and risk factors for obesity are widening. Addressing inequalities in
      obesity, therefore, has a very high profile on the public health and health
      services agendas. However, there is a lack of accessible policy-ready evidence on
      what works in terms of interventions to reduce inequalities in obesity. METHODS
      AND DESIGN: This article describes the protocol for a National Health Service
      Trust (NHS) National Institute for Health Research-funded systematic review of
      public health interventions at the individual, community and societal levels
      which might reduce socioeconomic inequalities in relation to obesity amongst
      children ages 0 to 18 years. The studies will be selected only if (1) they
      included a primary outcome that is a proxy for body fatness and (2) examined
      differential effects with regard to socioeconomic status (education, income,
      occupation, social class, deprivation and poverty) or the intervention was
      targeted specifically at disadvantaged groups (for example, children of the
      unemployed, lone parents, low income and so on) or at people who live in deprived
      areas. A rigorous and inclusive international literature search will be conducted
      for randomised and nonrandomised controlled trials, prospective and retrospective
      cohort studies (with and/or without control groups) and prospective repeat cross
      sectional studies (with and/or without control groups). The following electronic
      databases will be searched: MEDLINE, Embase, CINAHL, PsycINFO, Social Science
      Citation Index, ASSIA, IBSS, Sociological Abstracts and the NHS Economic
      Evaluation Database. Database searches will be supplemented with website and grey
      literature searches. No studies will be excluded on the basis of language,
      country of origin or publication date. Study inclusion, data extraction and
      quality appraisal will be conducted by two reviewers. Meta-analysis and narrative
      synthesis will be conducted. The main analysis will examine the effects of (1)
      individual, (2) community and (3) societal level public health interventions on
      socioeconomic inequalities in childhood obesity. Interventions will be
      characterised by their level of action and their approach to tackling
      inequalities. Contextual information on how such public health interventions are
      organised, implemented and delivered will also be examined. DISCUSSION: In this
      review, we consider public health strategies which reduce and prevent
      inequalities in the prevalence of childhood obesity, highlight any gaps in the
      evidence base and seek to establish how such public health interventions are
      organised, implemented and delivered. PROSPERO registration number:
      CRD42011001740.

PMID- 22587776
TI  - Tolerability of angiotensin-receptor blockers in patients with intolerance to
      angiotensin-converting enzyme inhibitors: a systematic review and meta-analysis.
AB  - BACKGROUND: Between 5% and 20% of patients treated with angiotensin-converting
      enzyme inhibitors (ACE inhibitors) develop intolerance. Angiotensin II type 1
      receptor antagonists (angiotensin receptor blockers [ARBs]) can be used as an
      alternative treatment. OBJECTIVE: In this study we aimed to evaluate the
      tolerability of ARBs in patients with intolerance to ACE inhibitors. DATA
      SOURCES: The electronic databases PubMed, MEDLINE/EMBASE via Dialog, CENTRAL, and
      ISI Web of Knowledge were searched. STUDY SELECTION: Randomized controlled trials
      (RCTs) evaluating ARBs in patients with intolerance to ACE inhibitors were
      selected. DATA SYNTHESIS: Risk ratio (RR) and 95% confidence intervals (CIs) were
      estimated assuming the random effects method. We found 11 RCTs comparing ARBs
      with ACE inhibitors, diuretics, or placebo, and one RCT comparing high-dose
      versus low-dose ARB. RESULTS: ARBs had fewer cough events versus ACE inhibitors
      (RR 0.37; 95% CI 0.28, 0.48). ARBs had drug discontinuation (RR 0.99; 95% CI
      0.84, 1.17) and cough risk (RR 1.01; 95% CI 0.74, 1.39) rates similar to placebo.
      Angioedema risk with ARBs was also similar to placebo (RR 1.62; 95% CI 0.17,
      15.79). Compared with placebo, hypotension (RR 2.63; 95% CI 1.77, 3.92), renal
      dysfunction (RR 2.07; 95% CI 1.45, 2.95) and hyperkalemia (RR 3.37; 95% CI 1.60,
      7.11) were more frequent with ARBs. CONCLUSIONS: ACE inhibitor rechallenge should
      be discouraged in patients with previous intolerance to ACE inhibitors due to a
      higher risk of cough. ARBs had cough and angioedema incidences similar to
      placebo. Despite a significantly higher incidence of hypotension, renal
      dysfunction and hyperkalemia, discontinuation of ARBs was similar to placebo.

PMID- 22587777
TI  - Insulin therapy improves protein metabolism in the critically ill.
AB  - Critical illness, trauma and burns are associated with profound metabolic
      abnormalities, of which protein catabolism, hyperglycemia and insulin resistance
      are hallmarks of these conditions. Increased protein breakdown and loss results
      in muscle wasting, weakness and diminished functioning. Interestingly,
      hyperglycemia and insulin resistance augment catabolic responses. Insulin, which
      is routinely administered to critically ill patients to prevent excessive
      hyperglycemia, also stimulates protein synthesis and prevents whole-body protein
      loss. The present commentary highlights the results of a recent study published
      in Critical Care and discusses whether moderate insulin therapy is equally as
      beneficial as conventional insulin therapy in preventing protein catabolism and
      loss. 

PMID- 22587778
TI  - The Regulatory Network of Pseudomonas aeruginosa.
AB  - BACKGROUND: Pseudomonas aeruginosa is an important bacterial model due to its
      metabolic and pathogenic abilities, which allow it to interact and colonize a
      wide range of hosts, including plants and animals. In this work we compile and
      analyze the structure and organization of an experimentally supported regulatory
      network in this bacterium. RESULTS: The regulatory network consists of 690 genes
      and 1020 regulatory interactions between their products (12% of total genes: 54%
      sigma and 16% of transcription factors). This complex interplay makes the third
      largest regulatory network of those reported in bacteria. The entire network is
      enriched for activating interactions and, peculiarly, self-activation seems to
      occur more prominent for transcription factors (TFs), which contrasts with other
      biological networks where self-repression is dominant. The network contains a
      giant component of 650 genes organized into 11 hierarchies, encompassing
      important biological processes, such as, biofilms formation, production of
      exopolysaccharide alginate and several virulence factors, and of the so-called
      quorum sensing regulons. CONCLUSIONS: The study of gene regulation in P.
      aeruginosa is biased towards pathogenesis and virulence processes, all of which
      are interconnected. The network shows power-law distribution -input degree -, and
      we identified the top ten global regulators, six two-element cycles, the longest
      paths have ten steps, six biological modules and the main motifs containing three
      and four elements. We think this work can provide insights for the design of
      further studies to cover the many gaps in knowledge of this important bacterial
      model, and for the design of systems strategies to combat this bacterium.

PMID- 22587780
TI  - Detection of antibodies against synthetic peptides mimicking ureases fragments in
      sera of rheumatoid arthritis patients.
AB  - Rheumatoid arthritis (RA) is a chronic disease with an autoimmunological
      background. RA is mostly characterized by systemic inflammation and injuries of
      synovial joints. There is a hypothesis that bacterial infections may be connected
      with development of the disease. It has been suggested that molecular mimicry
      between bacterial and human antigens may be one of possible mechanisms of RA
      development. One of potential antigens involved in this mechanism is urease -
      enzyme with high structural conservatism, occurring in pathogenic and commensal
      bacteria. We found that the level of antibodies against peptide mimicking urease
      "flap" region is significantly higher in sera from patients with rheumatoid
      arthritis in comparison with volunteer blood donor sera. We also observed that
      antibodies present in RA sera may bind not only specific peptide antigens but
      also peptides with a slightly different structure.

PMID- 22587779
TI  - Stringent response of Escherichia coli: revisiting the bibliome using literature
      mining.
AB  - BACKGROUND: Understanding the mechanisms responsible for cellular responses
      depends on the systematic collection and analysis of information on the main
      biological concepts involved. Indeed, the identification of biologically relevant
      concepts in free text, namely genes, tRNAs, mRNAs, gene products and small
      molecules, is crucial to capture the structure and functioning of different
      responses. RESULTS: In this work, we review literature reports on the study of
      the stringent response in Escherichia coli. Rather than undertaking the
      development of a highly specialised literature mining approach, we investigate
      the suitability of concept recognition and statistical analysis of concept
      occurrence as means to highlight the concepts that are most likely to be
      biologically engaged during this response. The co-occurrence analysis of core
      concepts in this stringent response, i.e. the (p)ppGpp nucleotides with gene
      products was also inspected and suggest that besides the enzymes RelA and SpoT
      that control the basal levels of (p)ppGpp nucleotides, many other proteins have a
      key role in this response. Functional enrichment analysis revealed that basic
      cellular processes such as metabolism, transcriptional and translational
      regulation are central, but other stress-associated responses might be elicited
      during the stringent response. In addition, the identification of less annotated
      concepts revealed that some (p)ppGpp-induced functional activities are still
      overlooked in most reviews. CONCLUSIONS: In this paper we applied a literature
      mining approach that offers a more comprehensive analysis of the stringent
      response in E. coli. The compilation of relevant biological entities to this
      stress response and the assessment of their functional roles provided a more
      systematic understanding of this cellular response. Overlooked regulatory
      entities, such as transcriptional regulators, were found to play a role in this
      stress response. Moreover, the involvement of other stress-associated concepts
      demonstrates the complexity of this cellular response.

PMID- 22587781
TI  - Biochemical property and in vivo efficacies of novel Val/Arg-rich antimicrobial
      peptide.
AB  - A novel alpha-helical antimicrobial peptide G6 rich in Val/Arg residues has been
      screened previously. In this study, we further evaluated the biochemical
      stability, interaction with whole bacteria, and in vivo therapeutic or
      prophylactic role of the peptide in Salmonella typhimurium-infected mice. The
      results showed that G6 exhibited strong resistance to pH, heat, and salts. But G6
      lost the antimicrobial activity when treated with proteolytic enzymes. G6 had no
      toxicity on mammalian cell. An intraperitoneal model of sepsis caused by
      Salmonella typhimurium was established in mice. G6 was administered
      intraperitoneally 1 h before or after mice were infected with Salmonella
      typhimurium. For the mice given peptide post-bacterial infection, the mortality
      of the mice and the peritoneal bacterial counts were significantly lower in the
      groups that were administered 2.5 mg/kg BW and 5.0 mg/kg BW of G6 (P < 0.05)
      compared to the PBS-treated group. Similar trend was obtained when G6 was given 1
      h prior to Salmonella typhimurium infection. Peptide-membrane experiments showed
      that G6 was effective in permeabilizing the outer and inner membrane in a dose
      dependent manner, indicating that the peptide targets the cell membrane. Taken
      together, the results revealed that the peptide G6 may provide a useful
      alternative to antibiotic agents to treat or prevent bacterial infections.

PMID- 22587782
TI  - Novel design of short antimicrobial peptides derived from the bactericidal domain
      of avian beta-defensin-4.
AB  - Short antimicrobial peptides were designed and synthesized by C-terminal
      truncation and residue substitution of avian beta-defensin-4. The biological
      activity of these peptides was examined to elucidate the quantitative structure
      activity relationships and find a lead peptide for the development of a novel
      antimicrobial peptide. The results showed that the truncation of the avian beta
      defensin-4 eliminated the hemolysis of the peptide. The GLI13 derivative,
      developed by substituting the Cys of the truncated peptide with Ile, led to
      increased antimicrobial activity. These results suggest that the peptides with
      antimicrobial activity can be derived by truncating the avian beta-defensin-4. We
      further developed the GLI13 derivative with an increased net charge by residue
      substitution. The results showed that the GLI13-5 with 5 net charges had the
      highest cell selectivty. An increase in the net charge from 6 to 8 did not result
      in the improvement of antimicrobial potency. Membrane-simulating experiments
      showed that the peptides preferentially bound to negatively charged phospholipids
      over zwitterionic phospholipids, which led to greater cell selectivity. A
      membrane depolarization assay showed that GLI13-5 killed bacteria by targeting
      the cytoplasmic membrane. These results suggest that the short peptide developed
      by truncation of linear beta-defensin may be a promising candidate for future
      antibacterial agents.

PMID- 22587783
TI  - Crystal structure of the Tum1 protein from the yeast Saccharomyces cerevisiae.
AB  - Yeast tRNA-thiouridine modification protein 1 (Tum1) plays essential role in the
      sulfur transfer process of Urm1 system, which in turn is involved in many
      important cellular processes. In the rhodanese-like domain (RLD), conserved
      cysteine residue is proved to be the centre of active site of sulfurtransferases
      and crucial for the substrate recognition. In this report, we describe the
      crystal structure of Tum1 protein at 1.90 A resolution which, despite consisting
      of two RLDs, has only one conserved cysteine residue in the C-terminal RLD. An
      unaccounted electron density is found near the active site, which might point to
      the new cofactor in the sulfur transfer mechanism.

PMID- 22587784
TI  - Biochemical characterization of thymidine monophosphate kinase from white spot
      syndrome virus: a functional domain from the viral ORF454.
AB  - Nucleotide phosphorylation is a key step towards DNA replication and during viral
      infections the maintenance of the nucleotide triphosphates pool is required.
      Deoxythymidine triphosphate (dTTP) is the unique nucleotide that is produced
      either by de novo or salvage pathways. Thymidine monophosphate kinase (TMK) is
      the enzyme that phosphorylates deoxythymidine monophosphate (dTMP) using
      adenosine triphosphate (ATP) as a phosphate group donor in presence of Mg2+
      yielding deoxythymidine diphosphate (dTDP) and adenosine diphosphate. The TMK
      region of the WSSV TK-TMK chimeric protein was overexpressed and purified. This
      recombinant protein had TMK activity, this is that dTMP was phosphorylated to
      dTDP and we found that the dimeric state of the protein was the functional and a
      theoretical structural model was built as such. Future work will focus towards a
      structural characterization as an antiviral target.

PMID- 22587785
TI  - Aqueous microwave-assisted solid-phase peptide synthesis using Fmoc strategy: in
      water synthesis of "difficult sequences".
AB  - A microwave assisted peptide synthesis in water using nanosized Fmoc-amino acids
      was developed. 5, 7, and 10 mer peptides (Leu-enkephalinamide, dermorphinamide,
      and a typical difficult sequence, ACP (65-74) peptide) were successfully
      synthesized in water according to Fmoc chemistry using water-dispersible
      nanoparticles with microwave irradiation.

PMID- 22587786
TI  - Characterization of glycine substitution mutations within the putative NAD+
      binding site of Bacillus licheniformis aldehyde dehydrogenase.
AB  - The NAD(+)-requiring enzymes of the aldehyde dehydrogenase (ALDH) family contain
      a glycine motif, GX1- 2GXXG, which is reminiscent of the fingerprint region of
      the Rossman fold, a conserved structural motif of the classical nicotinamide
      nucleotide-binding proteins. In this research, the role of three glycine residues
      situated within the putative NAD(+)-binding motif (211-GPGSSAG) together with
      Gly233 and Gly238 of Bacillus licheniformis ALDH (BlALDH) were probed by site
      directed mutatgenesis. Fifteen mutant BlALDHs were obtained by substitution of
      the indicated glycine residues with alanine, glutamate and arginine. Except for
      the Ala replacement at positions 211, 213, 217 and 238, the remaining mutant
      enzymes lost the dehydrogenase activity completely. Tryptophan fluorescence and
      far-UV circular dichroism spectra allowed us to discriminate BlALDH and the
      inactive mutant enzymes, and unfolding analyses further revealed that they had a
      different sensitivity towards temperature- and guanidine hydrochloride (GdnHCl)
      induced denaturation. BlALDH and the functional variants had a comparable T(m)
      value, but the value was reduced by more than 5.1 degrees C in the rest of mutant
      enzymes. Acrylamide quenching analysis showed that the inactive mutant enzymes
      had a dynamic quenching constant greater than that of BlALDH. Native BlALDH
      started to unfold beyond ~0.21 M GdnHCl and reached an unfolded intermediate,
      [GdnHCl](0.5, N-U), at 0.92 M equivalent to free energy change (DeltaG(N-U)(H2O))
      of 12.34 kcal/mol for the N -> U process, whereas the denaturation midpoints for
      mutant enzymes were 0.45-1.61 M equivalent to DeltaG(N-U)(H2O) of 0.31-4.35
      kcal/mol. Taken together, these results strongly suggest that the explored
      glycines are indeed important for the catalytic activity and structural stability
      of BlALDH.

PMID- 22587787
TI  - Principles, challenges and advances in ab initio protein structure prediction.
AB  - The gap between known protein sequences and structures is increasing rapidly and
      experimental methods alone will not be able to fill in this gap. Therefore it is
      necessary to use computational methods to predict protein structures. Template
      based modeling methods could be used for sequences, which have detectable
      relationship with sequences of one or more experimentally determined protein
      structures. For predicting the structure of proteins, which does not share a
      detectable sequence relationship with experimental structures, ab initio protein
      structure prediction techniques must be used. The methods under ab initio protein
      structure prediction category aim to predict the structure of a protein from the
      sequence information alone, without any explicit use of previously known
      structures. These methods use thermodynamic principles and try to identify the
      native structure of a protein as the global minimum of a potential energy
      landscape. However, such methods are computationally complex and are
      extraordinarily challenging. There has been significant progress in the
      development of ab inito protein structure prediction methods over the past few
      years. This review describes the basic principles, the complexity, challenges and
      recent progresses of ab initio protein structure prediction.

PMID- 22587788
TI  - SVM prediction of ligand-binding sites in bacterial lipoproteins employing shape
      and physio-chemical descriptors.
AB  - Bacterial lipoproteins play critical roles in various physiological processes
      including the maintenance of pathogenicity and numbers of them are being
      considered as potential candidates for generating novel vaccines. In this work,
      we put forth an algorithm to identify and predict ligand-binding sites in
      bacterial lipoproteins. The method uses three types of pocket descriptors, namely
      fpocket descriptors, 3D Zernike descriptors and shell descriptors, and combines
      them with Support Vector Machine (SVM) method for the classification. The three
      types of descriptors represent shape-based properties of the pocket as well as
      its local physio-chemical features. All three types of descriptors, along with
      their hybrid combinations are evaluated with SVM and to improve classification
      performance, WEKA-InfoGain feature selection is applied. Results obtained in the
      study show that the classifier successfully differentiates between ligand-binding
      and non-binding pockets. For the combination of three types of descriptors, 10
      fold cross-validation accuracy of 86.83% is obtained for training while the
      selected model achieved test Matthews Correlation Coefficient (MCC) of 0.534.
      Individually or in combination with new and existing methods, our model can be a
      very useful tool for the prediction of potential ligand-binding sites in
      bacterial lipoproteins.

PMID- 22587789
TI  - Enhanced hematopoietic differentiation toward erythrocytes from murine embryonic
      stem cells with HepG2-conditioned medium.
AB  - Embryonic stem cell (ESC) differentiation via embryoid body (EB) formation is an
      established method that generates the 3 germ layers. However, EB differentiation
      poses several problems including formation of heterogeneous cell populations.
      Previously, we have enhanced mesoderm derivation from murine ESCs (mESCs) using
      conditioned medium (CM) from HepG2 cells. We used this technique to direct
      hematopoiesis by generating "embryoid-like" colonies (ELCs) from mESCs without
      standard formation of EBs. Two predifferentiation conditions were tested: (1)
      mESCs cultured 3 days in standard predifferentiation medium (control) and (2)
      mESCs cultured 3 days in HepG2 CM (CM-mESCs). Both groups were then exposed to
      primary differentiation for 8 days (ELC-formation period) and 14 days of
      hematopoietic differentiation. Enhanced mesoderm formation was observed in the CM
      mESC group with an almost 5-fold increase in ELC formation (P <= 0.05) and higher
      expression of mesoderm genes-Brachyury-T, Goosecoid, and Flk-1-compared with
      those of control mESCs. Hematopoietic colony formation by CM-mESCs was also
      enhanced by 2-fold at days 7 and 14 with earlier colony commitment compared with
      those of control mESCs (P <= 0.05). This early clonogenic capacity was confirmed
      morphologically by the presence of nucleated erythrocytes and macrophages as
      early as day 7 in CM-mESC culture using standard 14-day colony-forming assay.
      Early expression of hematopoietic primitive (zeta-globin) and definitive (beta
      globin) erythroid genes and proteins was also observed by day 7 in CM-mESC
      cultures. These data indicate that hematopoietic cells more quickly differentiate
      from CM-mESCs, compared with those using standard EB approaches, and provide an
      efficient bioprocess platform for erythroid-specific differentiation of ESCs.

PMID- 22587790
TI  - Cultural repertoires and food-related household technology within colonia
      households under conditions of material hardship.
AB  - BSTRACT: INTRODUCTION: Mexican-origin women in the U.S. living in colonias (new
      destination Mexican-immigrant communities) along the Texas-Mexico border suffer
      from a high incidence of food insecurity and diet-related chronic disease.
      Understanding environmental factors that influence food-related behaviors among
      this population will be important to improving the well-being of colonia
      households. This article focuses on cultural repertoires that enable food choice
      and the everyday uses of technology in food-related practice by Mexican-immigrant
      women in colonia households under conditions of material hardship. Findings are
      presented within a conceptual framework informed by concepts drawn from
      sociological accounts of technology, food choice, culture, and material hardship.
      METHODS: Field notes were provided by teams of promotora-researchers (indigenous
      community health workers) and public-health professionals trained as participant
      observers. They conducted observations on three separate occasions (two half-days
      during the week and one weekend day) within eight family residences located in
      colonias near the towns of Alton and San Carlos, Texas. English observations were
      coded inductively and early observations stressed the importance of technology
      and material hardship in food-related behavior. These observations were further
      explored and coded using the qualitative data package Atlas.ti. RESULTS:
      Technology included kitchen implements used in standard and adapted
      configurations and household infrastructure. Residents employed tools across a
      range of food-related activities identified as forms of food acquisition,
      storage, preparation, serving, feeding and eating, cleaning, and waste
      processing. Material hardships included the quality, quantity, acceptability, and
      uncertainty dimensions of food insecurity, and insufficient consumption of
      housing, clothing and medical care. Cultural repertoires for coping with material
      hardship included reliance on inexpensive staple foods and dishes, and
      conventional and innovative technological practices. These repertoires expressed
      the creative agency of women colonia residents. Food-related practices were
      constrained by climate, animal and insect pests, women's gender roles,
      limitations in neighborhood and household infrastructure, and economic and
      material resources. CONCLUSIONS: This research points to the importance of
      socioeconomic and structural factors such as gender roles, economic poverty and
      material hardship as constraints on food choice and food-related behavior. In
      turn, it emphasizes the innovative practices employed by women residents of
      colonias to prepare meals under these constraints.

PMID- 22587791
TI  - Efficacy and safety of calcipotriene 0.005% foam for the treatment of plaque-type
      psoriasis: results of two multicenter, randomized, double-blind, vehicle
      controlled, phase III clinical trials.
AB  - BACKGROUND: Topical calcipotriene is frequently prescribed for the treatment of
      plaque-type psoriasis. Calcipotriene is currently available in the US as an
      ointment, a solution, a cream, and in a fixed-dose combination ointment with
      betamethasone dipropionate. Calcipotriene 0.005% has recently been formulated as
      a foam using a novel aqueous-based formulation to provide a new topical treatment
      option for patients with psoriasis. OBJECTIVE: The objective of this study was to
      evaluate the efficacy and safety of topical calcipotriene 0.005% foam for the
      treatment of mild to moderate plaque-type psoriasis. DESIGN: Two identical,
      randomized, double-blind, vehicle-controlled, 8-week phase III clinical trials.
      INTERVENTION: Subjects with plaque-type psoriasis affecting 2-20% of the body
      surface area, with an identifiable target lesion affecting the trunk or
      extremities, were randomized in a 2:1 ratio to calcipotriene foam (n = 437) or
      vehicle foam (n = 222). Study medication was applied twice daily for 8 weeks.
      OUTCOME MEASURES: Treatment success was defined as a score of 0 or 1 (clear or
      almost clear) on the Investigator's Static Global Assessment (ISGA) psoriasis
      rating scale and a minimum improvement of ISGA score of at least 2 grades from
      baseline. Predefined target lesions were assessed for erythema, scaling, and
      plaque thickness. Primary endpoint was the proportion of subjects in each
      treatment group who achieved treatment success after 8 weeks, analyzed on an
      intent-to-treat (ITT) basis. In the primary endpoint analysis, subjects missing 8
      week outcomes data were classified as treatment failures regardless of their
      outcomes at earlier evaluations. As part of the sensitivity analysis, a last
      observation-carried-forward (LOCF) approach to impute missing 8-week efficacy
      outcomes also examined treatment. Secondary endpoints included treatment success
      as a function of baseline ISGA score (mild or moderate), ISGA score of 0 or 1
      (clear or almost clear), and effects of treatment on target lesion. Adverse
      events (AEs) were recorded throughout the study. RESULTS: In the ITT population
      of Study 1, treatment success after 8 weeks was achieved by 14% of subjects in
      the calcipotriene foam group versus 7% of subjects in the vehicle foam group (p =
      0.058). In the LOCF analysis, treatment success was achieved by more subjects
      with calcipotriene foam than with vehicle foam (15% vs 7%; p = 0.034). In Study
      2, treatment success was achieved by more subjects in the calcipotriene foam
      group for the primary endpoint (27% vs 16%; p = 0.016) and the LOCF analysis (28%
      vs 16%; p = 0.010). Subjects in the calcipotriene foam group exhibited better
      response rates than did the vehicle foam group for most of the secondary
      outcomes. Calcipotriene foam was safe with an overall incidence of AEs similar to
      those experienced in the vehicle foam group. Application-site reactions were
      noted in approximately 1-2% of subjects in each group. No AE was reported in more
      than 2% of subjects in the calcipotriene foam group. Treatment was discontinued
      because of AEs in approximately 2% of subjects in both groups. CONCLUSIONS: In
      two identically designed, phase III clinical trials, calcipotriene 0.005% foam
      was safe and effective for the treatment of mild to moderate plaque-type
      psoriasis for up to 8 weeks. CLINICAL TRIAL REGISTRATION: Registered at
      clinicaltrials.gov: NCT00688519 and NCT00689481.

PMID- 22587793
TI  - Two new homoflavonoids from the fern Ophioglossum pedunculosum.
AB  - Two new homoflavonoids (1 and 2) were isolated from the fern Ophioglossum
      pedunculosum Desv. Their structures were elucidated on the basis of spectroscopic
      data to be 6-(3-methyl-2-buten-1-yl) ophioglonin (1) and ophioglonin 4'-O-beta-D
      glucopyranoside (2), respectively. In addition, the possible biogenetic pathway
      to compounds 1 and 2 was discussed.

PMID- 22587792
TI  - Chemical constituents from the fruits of Trichosanthes kirilowii.
AB  - Two new compounds, 1-deoxy-1-[2'-oxo-1'-pyrrolidinyl]-2-n-butyl-alpha
      fructofuranoside and isoarvenin III, were isolated from the fruits of
      Trichosanthes kirilowii Maxim, and their structures were established on the basis
      of spectroscopic methods.

PMID- 22587794
TI  - Enhancing effects of different dosages of borneol on pharmacokinetics of salvanic
      acid B after oral administration to rats.
AB  - The main purpose of this study was to illustrate the effect of borneol on
      pharmacokinetics of salvianolic acid B (SalB) in rats after oral administration
      of SalB with different doses of borneol. The concentrations of SalB in rat plasma
      were determined by an established and validated LC-MS/MS method. Our data showed
      that when 20, 40, and 80 mg kg-1 of borneol were orally administrated with SalB
      at 50 mg kg-1, C (max) of SalB was increased by 18.4%, 55.8%, and 103.2% compared
      with that of SalB alone. And AUC(0-t) of SalB in plasma was increased by 14.4%,
      48.5%, and 123.3%, respectively. The results indicated that borneol is able to
      enhance the intestinal absorption and relative bioavailability of SalB, with a
      positive dose-dependent relationship. The described herb-drug interactions might
      prove the scientific rationality of the compatible ratio of traditional Chinese
      medicines.

PMID- 22587795
TI  - Lipoxygenase inhibitory sphingolipids from Launaea nudicaulis.
AB  - Four new sphingolipids: nudicaulin A [(2S,3S,4R,14E)-2
      {[octadecanoyl]amino}tetraeicos-14-ene-1,3,4-triol; 1], nudicaulin B
      [(2S,3S,4R,14E)-2-{[(2R)-2-hydroxyoctadecanoyl]amino}tetraeicos-14-ene-1,3,4
      triol; 2], nudicaulin C [(2S,3S,4R,14E)-2-{[(2R)-2
      hydroxyoctadecanoyl]amino}tetraeicos-14-ene-1,3,4-triol-1-O-beta-D
      glucopyranoside; 3], and nudicaulin D [(2S,3S,4R)-2-{[(2R,3S,12E)-2,3
      dihydroxyeicos-12-enoyl]amino}octadecane-1,3,4-triol; 4] together with 1
      hexatriacontanol, beta-sitosterol, octadecyl 4-hydroxycinnamate, elaidic acid,
      cholesta-5,22-diene-3,7-diol, oleanolic acid, apigenin, and beta-sitosterol 3-O
      beta-D-glucopyranoside were isolated from the methanolic extract of the whole
      plant of Launaea nudicaulis. Their structures were elucidated using 1H and 13C
      NMR spectra and 2D NMR analyses (HMQC, HMBC, and COSY) in combination with mass
      spectrometry (EI-MS, HR-EI-MS, FAB-MS, and HR-FAB-MS) experiments and comparison
      with literature data of related compounds. Compounds 1-4 displayed moderate
      inhibitory potential against enzyme lipoxygenase in concentration-dependent
      manner with IC50 value ranges 103-193 MUM.

PMID- 22587796
TI  - A new flavan-3-ol from Artocarpus nitidus subsp. lingnanensis.
AB  - Further investigation on the stems of Artocarpus nitidus subsp. lingnanensis led
      to the isolation and characterization of a new flavan-3-ol, named
      artoflavanocoumarin, along with three known compounds (+)-catechin, (+)
      afzelechin 3-O-alpha-L-rhamnoside, and (+)-catechin 3-O-alpha-L-rhamnoside. Their
      structures were elucidated on the basis of spectroscopic data.

PMID- 22587797
TI  - Two new steroidal glycosides from Cynanchum amplexicaule.
AB  - Two new C21 steroidal glycosides were isolated from the EtOAc fraction of
      Cynanchum amplexicaule. Their structures were elucidated as amplexicogenin D-3-O
      beta-D-cymaropyranoside and stauntogenin -3-O-alpha-L-oleandropyranosyl-(1 -> 4)
      O-beta-D-digitoxopyranosyl-(1 -> 4)-O-beta-D-oleandropyranoside by spectroscopic
      analysis including 1D and 2D NMR experiments.

PMID- 22587799
TI  - Structure of a polysaccharide from Urtica fissa determined by NMR spectra.
AB  - A polysaccharide, isolated and purified from the aqueous extract of nettle plant
      Urtica fissa, was found to consist of D-glucose and D-arabinose. Molecular weight
      was determined to be Mn 4140. The NMR experiments (1H, 13C, 1H--1H COSY, TOCSY,
      HSQC, NOESY, and HMBC) revealed the structure as the following repeating unit: -
      >6)-alpha-D-Glcp-(1-->6)-alpha-D-Glcp-(1-->6)-beta-D-Glcp--(1-->5)-beta-D-Araf-(1
      ->3)-beta-D-Glcp-(1-->

PMID- 22587798
TI  - Partial synthesis and biological evaluation of bisbenzylisoquinoline alkaloids
      derivatives: potential modulators of multidrug resistance in cancer.
AB  - A series of new bisbenzylisoquinoline alkaloids was partially synthesized from
      tetrandrine and fangchinoline and evaluated for their ability to reverse P
      glycoprotein-mediated multidrug resistance (MDR) in cancer cells. All the test
      compounds increased the intracellular accumulation rate of rhodamine 123 in MDR
      cells (Bel7402 and HCT8), and most exhibited more potent MDR-reversing activity
      relative to the reference compound verapamil. Compounds 8, 10, 13, and 14
      enhanced intracellular accumulation of doxorubicin in Bel7402 and HCT8 cells.

PMID- 22587800
TI  - Chalcone-derived Diels-Alder adducts as NF-kappaB inhibitors from Morus alba.
AB  - A bioassay-guided phytochemical fractionation of the methanol extract of the
      Morus alba root barks led to the isolation of two chalcone-derived Diels-Alder
      adducts (1 and 2). Their structures were elucidated as kuwanon J 2,4,10"
      trimethyl ether (1) and kuwanon R (2) by means of spectroscopic methods. Both
      compounds strongly inhibited nuclear transcription factor.kappaB activity with
      the IC50 values of 4.65 and 7.38 MUM, respectively.

PMID- 22587801
TI  - Spiraeamide, new sphingolipid from Spiraea brahuica.
AB  - Spiraeamide, a new sphingolipid, has been isolated from the ethyl acetate-soluble
      fraction of the methanolic extract of the whole plant of Spiraea brahuica, along
      with marrubiin, 19-acetylmarrubenol, and 6-acetylmarruenol. Their structures were
      elucidated by 1H and 13C NMR spectra, and COSY, NOESY, HMQC, HMBC, EI-MS, and FAB
      MS experiments.

PMID- 22587802
TI  - A new triterpenoid saponin from Sanguisorba officinalis.
AB  - A new 19-oxo-18,19-seco-ursane-type triterpenoid saponin, named sanguisoside A
      (1), along with nine known triterpenoid saponins (2-10), was isolated from the
      roots of Sanguisorba officinalis. Their structures were determined on the basis
      of spectroscopic analysis and chemical method. Compounds 2 and 3 showed cytotoxic
      activity against SGC-7901, SMMC-7721, A549, and DU145 cell lines.

PMID- 22587803
TI  - Paratesticular desmoplastic small round cell tumour: an unusual tumour with an
      unusual fusion; cytogenetic and molecular genetic analysis combining RT-PCR and
      COBRA-FISH.
AB  - Desmoplastic small round cell tumour is a rare malignant tumour with a male to
      female ratio of 4:1. It manifests mostly at serosal sites. Here we present a case
      of a 28-year-old male patient, who presented with a fast growing paratesticular
      mass. On biopsy nests and cords of small round cells, without a clear
      morphological lineage of differentiation were seen. Occasionally desmoplatic
      small round cell tumour shows different lines of differentiation. An unequivocal
      histological diagnosis might be difficult in such cases. Here we demonstrate by a
      combination of methods the characteristic immunohistochemical profile and -
      albeit unusual - molecular background and discuss the eventual link with Ewing
      sarcoma.Immunohistochemical studies showed a membranous staining of Keratine
      AE1/3 and a dot-like staining of Desmine, confirming its diagnosis. Using COBRA
      FISH following a metaphase approach we demonstrated a balanced translocation,
      t(11;22)(p13;q12) and in RT-PCR formation of the EWSR1-WT1 fusion product, a
      specific translocation of desmoplastic round cell tumour. The fusion involves
      exon 9 of EWSR1 to exon 8 of WT1, an unusual fusion product, though earlier
      described in a case of a desmoplastic small round cell tumour of the hand. The
      EWSR1-WT1 chimera seems to function as an oncogenic transcription factor. Here
      the zinc finger domain of the WT1 acts with affinity with certain promoter
      domains influencing the expression of various downstream proteins such as: PDGFA,
      PAX2, insulin-like growth factor 1 receptor, epidermal growth factor receptor,
      IL2 receptor beta, BAIAP3, MLF1, TALLA-1, LRRC15 and ENT. We discuss their
      potential oncogenic roles and potential therapeutic consequences.

PMID- 22587804
TI  - Protocol for a systematic review of prognosis after mild traumatic brain injury:
      an update of the WHO Collaborating Centre Task Force findings.
AB  - BACKGROUND: Mild traumatic brain injury (MTBI) is a major public-health concern
      and represents 70-90% of all treated traumatic brain injuries. The last best
      evidence synthesis, conducted by the WHO Collaborating Centre for Neurotrauma,
      Prevention, Management and Rehabilitation in 2002, found few quality studies on
      prognosis. The objective of this review is to update these findings.
      Specifically, we aim to describe the course, identify modifiable prognostic
      factors, determine long-term sequelae, and identify effects of interventions for
      MTBI. Finally, we will identify gaps in the literature, and make recommendations
      for future research. METHODS: The databases MEDLINE, PsychINFO, Embase, CINAHL
      and SPORTDiscus were systematically searched (2001 to date). The search terms
      included 'traumatic brain injury', 'craniocerebral trauma', 'prognosis', and
      'recovery of function'. Reference lists of eligible papers were also searched.
      Studies were screened according to pre-defined inclusion and exclusion criteria.
      Inclusion criteria included original, published peer-reviewed research reports in
      English, French, Swedish, Norwegian, Danish and Spanish, and human participants
      of all ages with an accepted definition of MTBI. Exclusion criteria included
      publication types other than systematic reviews, meta-analyses, randomized
      controlled trials, cohort studies, and case-control studies; as well as
      cadaveric, biomechanical, and laboratory studies. All eligible papers were
      critically appraised using a modification of the Scottish Intercollegiate
      Guidelines Network (SIGN) criteria. Two reviewers performed independent, in-depth
      reviews of each eligible study, and a third reviewer was consulted for
      disagreements. Data from accepted papers were extracted into evidence tables, and
      the evidence was synthesized according to the modified SIGN criteria. CONCLUSION:
      The results of this study form the basis for a better understanding of recovery
      after MTBI, and will allow development of prediction tools and recommendation of
      interventions, as well as informing health policy and setting a future research
      agenda.

PMID- 22587805
TI  - Is there a gender difference in anatomic features of incisive canal and maxillary
      environmental bone?
AB  - OBJECTIVES: The effect of gender on anatomic structures and various body systems
      were illustrated in the literature. The purpose of this study was to identify the
      influence of gender and tooth loss on incisive canal characteristics and buccal
      bone dimensions in the anterior maxilla. MATERIALS AND METHODS: Computed
      tomographies (CTs) of 417 male and 516 female patients in four dental clinics
      were included in this study. The diameter and the length of the incisive canal;
      width and the length of the bone anterior to the canal; palatal bone length, root
      length, and root width of the central incisor teeth were measured and recorded
      from CT sections. RESULTS: Mean incisive canal length was 11.96 +/- 2.73 mm and
      10.39 +/- 2.47 mm in men and women, respectively, (P < 0.05). In men, mean canal
      diameter was 2.79 +/- 0.94 mm whereas in women it was 2.43 +/- 0.85 mm and this
      difference was statistically significant (P < 0.05). Men had significant higher
      buccal bone dimensions (length and width of the bone anterior to the canal) than
      women. Absence of teeth in the anterior maxilla decreased incisive canal length
      and buccal bone dimensions; however, canal diameter remain unchanged.
      CONCLUSIONS: Present results suggested a gender related differences in anatomic
      features of incisive canal and surrounding buccal bone. In addition, crestal
      canal diameter, buccal bone length, and thickness parameters might be different
      in distinct countries.

PMID- 22587806
TI  - Anesthesia with sevoflurane and remifentanil under spontaneous respiration
      assisted with high-frequency jet ventilation for tracheobronchial foreign body
      removal in 586 children.
AB  - BACKGROUND: Foreign body aspiration is a common life-threatening event in young
      children. Tracheobronchial foreign body removal is usually performed by rigid
      tracheobronchoscopy under general anesthesia. Anesthetic and ventilation
      techniques vary greatly among anesthesiologists and institutions. In the present
      retrospective study, we report our anesthetic experience over 5 years. We
      describe complications and outcomes and analyze the clinical characteristics of
      anesthesia and ventilation. METHODS: We retrospectively reviewed relevant
      clinical findings of 586 pediatric patients treated with rigid
      tracheobronchoscopy under general anesthesia. All procedures were performed under
      inhaled sevoflurane anesthesia combined with remifentanil infusion, with
      spontaneous respiration assisted by high-frequency jet ventilation (HFJV) and
      topical airway anesthesia. RESULTS: Among 586 patients, the foreign body was
      successfully removed by rigid tracheobronchoscopy in 558 patients, and no foreign
      body was found in 28 patients. Laryngospasm was observed during the procedure in
      five patients. Hypoxemia was observed in 15 patients (2.6%). No severe
      complications or deaths occurred. The mean operation time was 22 min and the
      average hospital stay was 2 days. CONCLUSION: Inhaled sevoflurane anesthesia
      combined with remifentanil infusion, with spontaneous respiration assisted by
      HFJV and topical airway anesthesia, is safe and effective for tracheobronchial
      foreign body removal.

PMID- 22587807
TI  - The interpupillary distance in adult Caucasian subjects, with reference to
      'readymade' reading spectacle centration.
AB  - PURPOSE: The magnitude of the far interpupillary distance (FIPD) has recognized
      significance within and beyond clinical optometry. Quantitative information
      regarding the lesser-reported near parameter (NIPD) would similarly be of
      interest, and could be of relevance with regard to the visual comfort obtained
      with 'readymade' reading spectacles. METHODS: Mensuration statistics relating to
      the FIPD and NIPD are presented, as collated from the spectacle dispensing
      records of n = 1354 healthy Caucasian presbyopic subjects. The FIPD data were
      partitioned across 4 age bands (by decade, 41-80 years of age): the NIPD data
      were distributed across seven nominal reading powers (in 0.50 D steps, +1.00 to
      +4.00 D). The results of these analyses are considered here, along with their
      potential application. RESULTS: Consistent gender (male > female) and
      classification (far > near) differences in IPD (both of approximately 3 mm) were
      confirmed throughout these data. The magnitude of the adult FIPD is in accord
      with previously published results; this dimension is now supplemented by NIPD
      values, whose relationship with total near power is also described. CONCLUSIONS:
      This new anthropometric survey indicates that inter- and intra-gender interocular
      facial measurement stability is a characteristic of presbyopic subjects. It is
      suggested that across the anticipated range of age and total reading power
      requirement of Caucasian (White Northern European) wearers of 'readymade' reading
      spectacles, adoption of a standard optical centration distance of 61 mm would be
      universally appropriate.

PMID- 22587808
TI  - Amphiphilic self-assembled polymeric copper catalyst to parts per million levels:
      click chemistry.
AB  - Self-assembly of copper sulfate and a poly(imidazole-acrylamide) amphiphile
      provided a highly active, reusable, globular, solid-phase catalyst for click
      chemistry. The self-assembled polymeric Cu catalyst was readily prepared from
      poly(N-isopropylacrylamide-co-N-vinylimidazole) and CuSO(4) via coordinative
      convolution. The surface of the catalyst was covered with globular particles tens
      of nanometers in diameter, and those sheetlike composites were layered to build
      an aggregated structure. Moreover, the imidazole units in the polymeric ligand
      coordinate to CuSO(4) to give a self-assembled, layered, polymeric copper
      complex. The insoluble amphiphilic polymeric imidazole Cu catalyst with even 4.5
      45 mol ppm drove the Huisgen 1,3-dipolar cycloaddition of a variety of alkynes
      and organic azides, including the three-component cyclization of a variety of
      alkynes, organic halides, and sodium azide. The catalytic turnover number and
      frequency were up to 209000 and 6740 h(-1), respectively. The catalyst was
      readily reused without loss of catalytic activity to give the corresponding
      triazoles quantitatively.

PMID- 22587809
TI  - Apolipoprotein M--a new biomarker in sepsis.
AB  - Sepsis is one of the leading causes of mortality in non-cardiac intensive care
      units, and the need for markers of progression and severity are high. Also,
      treatment of sepsis is highly debated and potential new targets of treatment are
      of great interest. In the previous issue of Critical Care Kumaraswamy and
      colleagues have investigated whether plasma apolipoprotein M (apoM) is affected
      during different grades of sepsis, septic shock and systemic inflammatory
      response syndrome. Interestingly, plasma apoM was significantly decreased in all
      groups of patients with a relationship to severity of disease. This identifies
      apoM as a potential new biomarker in sepsis. It also underscores the possibility
      that altered high-density lipoprotein in sepsis patients can affect the course of
      disease. Thus, since apoM is the carrier of Sphingosine-1-P (S1P), a molecule
      with great influence on vascular barrier function, the study presented raises the
      interest and relevance for further studies of apoM and S1P in relation to sepsis
      and inflammation. 

PMID- 22587811
TI  - Messages about methadone and buprenorphine in reality television: a content
      analysis of celebrity rehab with Dr. Drew.
AB  - Medication-assisted treatment for opioid dependence is safe and effective, yet
      negative perceptions about methadone and buprenorphine may discourage patients
      from entering treatment. One source of information that may influence viewers'
      perceptions is television. We performed a content analysis of a popular reality
      television program on addiction treatment. Although many patients had histories
      of opioid use, there were no positive messages about methadone or buprenorphine.
      The two main messages were that they (1) are primarily drugs of abuse, and (2)
      not acceptable treatment options. These messages reinforce negative stereotypes
      and may perpetuate stigma. There were multiple missed opportunities to provide
      evidence-based information.

PMID- 22587810
TI  - Predicted Relative Metabolomic Turnover (PRMT): determining metabolic turnover
      from a coastal marine metagenomic dataset.
AB  - BACKGROUND: The world's oceans are home to a diverse array of microbial life
      whose metabolic activity helps to drive the earth's biogeochemical cycles.
      Metagenomic analysis has revolutionized our access to these communities,
      providing a system-scale perspective of microbial community interactions.
      However, while metagenome sequencing can provide useful estimates of the relative
      change in abundance of specific genes and taxa between environments or over time,
      this does not investigate the relative changes in the production or consumption
      of different metabolites. RESULTS: We propose a methodology, Predicted Relative
      Metabolic Turnover (PRMT) that defines and enables exploration of metabolite
      space inferred from the metagenome. Our analysis of metagenomic data from a time
      series study in the Western English Channel demonstrated considerable
      correlations between predicted relative metabolic turnover and seasonal changes
      in abundance of measured environmental parameters as well as with observed
      seasonal changes in bacterial population structure. CONCLUSIONS: The PRMT method
      was successfully applied to metagenomic data to explore the Western English
      Channel microbial metabalome to generate specific, biologically testable
      hypotheses. Generated hypotheses linked organic phosphate utilization to
      Gammaproteobactaria, Plantcomycetes, and Betaproteobacteria, chitin degradation
      to Actinomycetes, and potential small molecule biosynthesis pathways for
      Lentisphaerae, Chlamydiae, and Crenarchaeota. The PRMT method can be applied as a
      general tool for the analysis of additional metagenomic or transcriptomic
      datasets.

PMID- 22587812
TI  - Successful completion: an examination of factors influencing drug court
      completion for white and non-white male participants.
AB  - This research examines the influence of demographic and legal factors on the
      successful completion of the Seahawk Drug Treatment Court Program for White and
      Non-White male participants. Located in a medium-size city, the program targets
      male felony offenders and has been in operation for more than 10 years. The
      research sample is comprised of 526 participants with a program disposition
      between January 1, 2005 and September 30, 2010. Using race-specific logistic
      regression models, results reveal both similarities and differences among these
      groups. The implications and limitations of this research are discussed, as well
      as avenues for future research.

PMID- 22587813
TI  - Clinical nurses' expressions of the emotions related to caring and coping with
      cancer patients in Pakistan: a qualitative study.
AB  - Nursing in Pakistan is a developing profession. This was the first study to
      examine nurses' views and emotions related to nursing cancer patients in an
      oncology hospital in Pakistan. Semi-structured interviews explored the concept of
      emotions and their interpretation by nurses. A purposive sample of nurses was
      recruited from hospital departments and wards. Twenty nurses were interviewed.
      Data were analysed using thematic analysis. Four themes emerged from the data.
      These were: the importance of expressing empathy, feelings of helplessness,
      developing emotions and tailoring moods to match the patient environment. The
      significance of the patients' cancer journey was multilayered with highs and lows
      that were imbued with the hope of cure and remission and by an emotional
      catalogue of feelings; joy at nursing patients in remission to helplessness for
      patients in advanced stage. Male domination and a negative public perception of
      cancer were significant issues that nurses acknowledged. The strategies nurses
      use to manage emotional situations needs further research with workshops to
      enhance nurse's skills in emotional intelligence when caring for cancer patients.

PMID- 22587814
TI  - A phenomenological analysis of disaster-related experiences in fire and emergency
      medical services personnel.
AB  - This article explores the experiences of fire and Emergency Medical Services
      (EMS) personnel during and immediately after a technological event using a
      phenomenological approach. Personnel engaged in the rescue operations during and
      immediately after the Ghislenghien gas explosion reflected upon their experiences
      in their responses to a specially designed, self-reporting questionnaire that
      included open-ended questions. Firefighters reported more perceived threat and
      direct exposure to death than did EMS personnel. Qualitative analysis indicates
      that the central characteristics of this potentially traumatizing event were the
      suddenness and massiveness of the impact, and the fact that it involved young
      victims and/or multiple deaths. With regard to emotions, powerlessness, horror,
      fear, a sense of apocalypse, and grief were experienced by both firefighters and
      EMS personnel. Firefighters noted that the death of colleagues, the involvement
      of friends and family, the massive impact, and exposure to the burned victims
      were most shocking. Emergency Medical Services personnel and in-hospital staff
      reported the impact, the confrontation with death, the involvement of friends and
      family, and the pain, suffering, and screaming of burned victims as the most
      shocking aspects of this event. Qualitative differences in the lived experiences
      of firefighters, EMS personnel, and in-hospital staff might be explained by
      differences in life threat, contact with death, and various degrees of training.

PMID- 22587815
TI  - An empirical study using permutation-based resampling in meta-regression.
AB  - BACKGROUND: In meta-regression, as the number of trials in the analyses
      decreases, the risk of false positives or false negatives increases. This is
      partly due to the assumption of normality that may not hold in small samples.
      Creation of a distribution from the observed trials using permutation methods to
      calculate P values may allow for less spurious findings. Permutation has not been
      empirically tested in meta-regression. The objective of this study was to perform
      an empirical investigation to explore the differences in results for meta
      analyses on a small number of trials using standard large sample approaches
      verses permutation-based methods for meta-regression. METHODS: We isolated a
      sample of randomized controlled clinical trials (RCTs) for interventions that
      have a small number of trials (herbal medicine trials). Trials were then grouped
      by herbal species and condition and assessed for methodological quality using the
      Jadad scale, and data were extracted for each outcome. Finally, we performed meta
      analyses on the primary outcome of each group of trials and meta-regression for
      methodological quality subgroups within each meta-analysis. We used large sample
      methods and permutation methods in our meta-regression modeling. We then compared
      final models and final P values between methods. RESULTS: We collected 110 trials
      across 5 intervention/outcome pairings and 5 to 10 trials per covariate. When
      applying large sample methods and permutation-based methods in our backwards
      stepwise regression the covariates in the final models were identical in all
      cases. The P values for the covariates in the final model were larger in 78%
      (7/9) of the cases for permutation and identical for 22% (2/9) of the cases.
      CONCLUSIONS: We present empirical evidence that permutation-based resampling may
      not change final models when using backwards stepwise regression, but may
      increase P values in meta-regression of multiple covariates for relatively small
      amount of trials.

PMID- 22587816
TI  - Role of NADPH oxidase/ROS in pro-inflammatory mediators-induced airway and
      pulmonary diseases.
AB  - Reactive oxygen species (ROS) are products of normal cellular metabolism and are
      known to act as second messengers. Under physiological conditions, ROS
      participate in maintenance of cellular 'redox homeostasis' in order to protect
      cells against oxidative stress. In addition, regulation of redox state is
      important for cell activation, viability, proliferation, and organ function.
      However, overproduction of ROS, most frequently due to excessive stimulation of
      either reduced nicotinamide adenine dinucleotide phosphate (NADPH) by pro
      inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-1beta (IL-1beta) or the mitochondrial electron transport chain and
      xanthine oxidase, results in oxidative stress. Oxidative stress is a deleterious
      process that leads to airway and lung damage and consequently to several
      respiratory inflammatory diseases/injuries, including acute respiratory distress
      syndrome (ARDS), asthma, cystic fibrosis (CF), and chronic obstructive pulmonary
      disease (COPD). Many of the known inflammatory target proteins, such as matrix
      metalloproteinase-9 (MMP-9), intercellular adhesion molecule-1 (ICAM-1), vascular
      cell adhesion molecule-1 (VCAM-1), cyclooxygenase-2 (COX-2), and cytosolic
      phospholipase A(2) (cPLA(2)), are associated with NADPH oxidase activation and
      ROS overproduction in response to pro-inflammatory mediators. Thus, oxidative
      stress regulates both key inflammatory signal transduction pathways and target
      proteins involved in airway and lung inflammation. In this review, we discuss
      mechanisms of NADPH oxidase/ROS in the expression of inflammatory target proteins
      involved in airway and lung diseases. Knowledge of the mechanisms of ROS
      regulation could lead to the pharmacological manipulation of antioxidants in
      airway and lung inflammation and injury.

PMID- 22587818
TI  - What is the best management strategy for a 20-year-old woman with premature
      ovarian failure?
AB  - The diagnosis of premature ovarian failure (POF) for a 20-year-old woman is
      devastating and will impact on many areas of her life. She deserves prompt
      confirmation of the diagnosis and accurate, honest information about the
      condition including the chances of conception and long-term health issues. She
      should be offered investigation of aetiology, although this may be hard to
      establish, and assessment of associated medical conditions. Oestrogen replacement
      should be advised for long-term use until the normal age of menopause, and she
      should be fully counselled on the benefits and risks of hormone replacement and
      her options of which preparation to take. Long-term follow-up is needed, and this
      is likely to require multidisciplinary input, including that from a
      gynaecologist, clinical psychologist and fertility team. POF may not be the
      appropriate terminology for this condition. Ovarian function often fluctuates in
      young women with POF, who may continue to menstruate occasionally and even
      conceive spontaneously. In view of this unpredictability, 'premature ovarian
      insufficiency' is a better description of the condition and carries a less
      negative connotation than 'ovarian failure' which can cause great distress. We
      recommend that the condition is termed 'premature ovarian insufficiency'
      (Clinical Endocrinology 2008;68:499).

PMID- 22587817
TI  - Structure-activity relationships for the binding of polymyxins with human alpha-1
      acid glycoprotein.
AB  - Here, for the first time, we have characterized binding properties of the
      polymyxin class of antibiotics for human alpha-1-acid glycoprotein (AGP) using a
      combination of biophysical techniques. The binding affinity of colistin,
      polymyxin B, polymyxin B(3), colistin methansulfonate, and colistin nona-peptide
      was determined by isothermal titration calorimetry (ITC), surface plasma
      resonance (SPR) and fluorometric assay methods. All assay techniques indicated
      colistin, polymyxin B and polymyxin B(3) display a moderate binding affinity for
      AGP. ITC and SPR showed there was no detectable binding affinity for colistin
      methansulfonate and colistin nona-peptide, suggesting both the positive charges
      of the diaminobutyric acid (Dab) side chains and the N-terminal fatty acyl chain
      of the polymyxin molecule are required to drive binding to AGP. In addition, the
      ITC and fluorometric data suggested that endogenous lipidic substances bound to
      AGP provide part of the polymyxin binding surface. A molecular model of the
      polymyxin B(3)-AGP F1*S complex was presented that illustrates the pivotal role
      of the N-terminal fatty acyl chain and the D-Phe6-L-Leu7 hydrophobic motif of
      polymyxin B(3) for binding to the cleft-like ligand binding cavity of AGP F1*S
      variant. The model conforms with the entropy driven binding interaction
      characterized by ITC which suggests hydrophobic interactions coupled to
      desolvation events and conformational changes are the primary driving force for
      polymyxins binding to AGP. Collectively, the data are consistent with a role of
      this acute-phase reactant protein in the transport of polymyxins in plasma.

PMID- 22587819
TI  - Risk of catheter-associated infection in young hematology/oncology patients
      receiving long-term peripheral nerve blocks.
AB  - BACKGROUND: Continuous peripheral nerve blocks (CPNBs) are increasingly used to
      control postoperative and chronic pain. At our pediatric oncology institution,
      the duration of CPNBs is often prolonged. The risk of catheter-associated
      infection with prolonged CPNBs has not been previously investigated. AIM: We
      analyzed the incidence of CPNB-related infection and its relation to catheter
      duration, catheter site, intensive care stay, and antibiotic coverage. METHODS:
      All CPNBs placed at our institution between August 1, 2005 and October 31, 2010
      were studied. Primary diagnosis and the site, indication, duration, and
      infectious adverse effects of CPNBs were obtained from our Pain Service QI
      database. Patients' age and sex, antibiotic administration, and number of days in
      intensive care were collected from patients' medical records. RESULTS: The use of
      179 catheters in 116 patients was evaluated. Mean age at CPNB placement was 15.1
      years (median, 14.7; range, 0.4-26.9). The most frequent indication for CPNB was
      surgery (89.4%), most commonly orthopedic (78.8%). Mean CPNB duration was 7.2
      days (median, 5.0; range, 1-81 days). Two cases (1.12%) of CPNBs developed signs
      of infection, both associated with femoral catheters. The infections were mild
      and necessitated catheter removal at days 10 and 13, respectively. CONCLUSION:
      Nerve block catheter-associated infections are infrequent at our institution
      despite prolonged CPNB use. Both patients with infection had femoral catheters
      and prolonged catheter (>= 10 days) use.

PMID- 22587820
TI  - Exercise training in chronic kidney disease patients.
AB  - Chronic kidney disease (CKD) is a major public health problem that affects an
      estimated 1.7 million Australians. Patients with CKD commonly progress to end
      stage kidney disease (ESKD) requiring dialysis and/or kidney transplantation.
      They are at high risk of cardiovascular disease and many die from this prior to
      reaching ESKD. Few therapies are available to slow CKD progression and reduce
      cardiovascular morbidity and mortality. The benefit of exercise training has been
      well demonstrated in a range of disease conditions including ESKD and was
      recently highlighted by a systematic review in haemodialysis patients and a
      recent Cochrane review of all stages of CKD. However, the effects of exercise
      training in patients with CKD have not been extensively investigated. Our
      systematic search of the literature found only ten clinical trials in this area.
      The aim of this review is to review these studies, and to discuss the findings,
      safety considerations and suggest future areas of research. Overall, the majority
      of the studies are small, non-randomized, non-controlled trials. They have found
      that exercise training can increase exercise capacity, improve muscle strength
      and function, decrease blood pressure, and improve inflammation and oxidative
      stress biomarkers. The effects of exercise training on kidney function,
      cardiovascular disease and quality of life are unknown. Studies are needed to
      answer these questions and develop evidence-based exercise training guidelines
      for individuals with CKD.

PMID- 22587821
TI  - The potential for high-intensity interval training to reduce cardiometabolic
      disease risk.
AB  - In the US, 34% of adults currently meet the criteria for the metabolic syndrome
      defined by elevated waist circumference, plasma triglycerides (TG), fasting
      glucose and/or blood pressure, and decreased high-density lipoprotein cholesterol
      (HDL-C). While these cardiometabolic risk factors can be treated with medication,
      lifestyle modification is strongly recommended as a first-line approach. The
      purpose of this review is to focus on the effect of physical activity
      interventions and, specifically, on the potential benefits of incorporating
      higher intensity exercise. Several recent studies have suggested that compared
      with continuous moderate exercise (CME), high-intensity interval training (HIT)
      may result in a superior or equal improvement in fitness and cardiovascular
      health. HIT is comprised of brief periods of high-intensity exercise interposed
      with recovery periods at a lower intensity. The premise of using HIT in both
      healthy and clinical populations is that the vigorous activity segments promote
      greater adaptations via increased cellular stress, yet their short length, and
      the ensuing recovery intervals, allow even untrained individuals to work harder
      than would otherwise be possible at steady-state intensity. In this review, we
      examine the impact of HIT on cardiometabolic risk factors, anthropometric
      measures of obesity and cardiovascular fitness in both healthy and clinical
      populations with cardiovascular and metabolic disease. The effects of HIT versus
      CME on health outcomes were compared in 14 of the 24 studies featuring HIT.
      Exercise programmes ranged from 2 weeks to 6 months. All 17 studies that measured
      aerobic fitness and all seven studies that measured insulin sensitivity showed
      significant improvement in response to HIT, although these changes did not always
      exceed responses to CME comparison groups. A minimum duration of 12 weeks was
      necessary to demonstrate improvement in fasting glucose in four of seven studies
      (57%). A minimum duration of 8 weeks of HIT was necessary to demonstrate
      improvement in HDL-C in three of ten studies (30%). No studies reported that HIT
      resulted in improvement of total cholesterol, low-density lipoprotein cholesterol
      (LDL-C), or TG. At least 12 weeks of HIT was required for reduction in blood
      pressure to emerge in five studies of participants not already being treated for
      hypertension. A minimum duration of 12 weeks was necessary to see consistent
      improvement in the six studies that examined anthropometric measures of obesity
      in overweight/obese individuals. In the 13 studies with a matched-exercise-volume
      CME group, improvement in aerobic fitness in response to HIT was equal to (5
      studies), or greater than (8 studies) in response to CME. Additionally, HIT has
      been shown to be safe and effective in patients with a range of cardiac and
      metabolic dysfunction. In conclusion, HIT appears to promote superior
      improvements in aerobic fitness and similar improvements in some cardiometabolic
      risk factors in comparison to CME, when performed by healthy subjects or clinical
      patients for at least 8-12 weeks. Future studies need to address compliance and
      efficacy of HIT in the real world with a variety of populations.

PMID- 22587822
TI  - Exercise-training intervention studies in competitive swimming.
AB  - Competitive swimming has a long history and is currently one of the largest
      Olympic sports, with 16 pool events. Several aspects separate swimming from most
      other sports such as (i) the prone position; (ii) simultaneous use of arms and
      legs for propulsion; (iii) water immersion (i.e. hydrostatic pressure on thorax
      and controlled respiration); (iv) propulsive forces that are applied against a
      fluctuant element; and (v) minimal influence of equipment on performance.
      Competitive swimmers are suggested to have specific anthropometrical features
      compared with other athletes, but are nevertheless dependent on physiological
      adaptations to enhance their performance. Swimmers thus engage in large volumes
      of training in the pool and on dry land. Strength training of various forms is
      widely used, and the energetic systems are addressed by aerobic and anaerobic
      swimming training. The aim of the current review was to report results from
      controlled exercise training trials within competitive swimming. From a
      structured literature search we found 17 controlled intervention studies that
      covered strength or resistance training, assisted sprint swimming, arms-only
      training, leg-kick training, respiratory muscle training, training the energy
      delivery systems and combined interventions across the aforementioned categories.
      Nine of the included studies were randomized controlled trials. Among the
      included studies we found indications that heavy strength training on dry land
      (one to five repetitions maximum with pull-downs for three sets with maximal
      effort in the concentric phase) or sprint swimming with resistance towards
      propulsion (maximal pushing with the arms against fixed points or pulling a
      perforated bowl) may be efficient for enhanced performance, and may also possibly
      have positive effects on stroke mechanics. The largest effect size (ES) on
      swimming performance was found in 50 m freestyle after a dry-land strength
      training regimen of maximum six repetitions across three sets in relevant muscle
      groups (ES 1.05), and after a regimen of resisted- and assisted-sprint training
      with elastic surgical tubes (ES 1.21). Secondly, several studies suggest that
      high training volumes do not pose any immediate advantage over lower volumes
      (with higher intensity) for swim performance. Overall, very few studies were
      eligible for the current review although the search strategy was broad and fairly
      liberal. The included studies predominantly involved freestyle swimming and,
      overall, there seems to be more questions than answers within intervention-based
      competitive swimming research. We believe that this review may encourage other
      researchers to pursue the interesting topics within the physiology of competitive
      swimming.

PMID- 22587823
TI  - Fibrosarcomatous changes and expression of CD34+ and apolipoprotein-D in
      dermatofibrosarcoma protuberans.
AB  - BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a relatively common soft
      tissue tumor. A more aggressive appearing fibrosarcoma may arise in DFSP,
      changing its biological behavior. CD34 and apolipoprotein-D are highly expressed
      in DFSP, but their prognostic significance is uncertain. METHODS: DFSP and
      fibrosarcomatous-DFSP (FS-DFSP) patients referred to our institute between 1982
      and 2009 were identified. Fibrosarcomatous changes, expression of CD34 and
      apolipoprotein-D were evaluated. RESULTS: 40 patients, (median age 43 years, 55%
      males) were identified. Tumor was located in the limbs in 60%, in the trunk in
      40%. Thirty-seven patients had localized and 3 had metastatic disease. Thirteen
      (32%) patients were FS-DFSP. All but one underwent surgery with adequate surgical
      margins in 72%. 7 FS-DFSP received also radiotherapy (RT). Chemotherapy was
      administered to 3 patients with FS-DFSP. With a median follow-up of 49 months,
      the 5-OS was 90%. Local recurrence rate was 23%: 42% FS-DFSP, 15% DFSP.
      Metastases developed in three FS-DFSP patients. The 5-year EFS was 70% in
      localized patients. Histology (DFSP 75% vs. FS-DFSP 52%, p = 0.002), surgical
      margins (adequate 74% vs. inadequate 55%, p = 0.02), site (limb 47% vs. trunk
      100%), CD34 expression (CD34 positive: 70% vs. CD34 negative: 33%, p = 0.05), and
      apolipoprotein-D expression (Apo-D positive: 73% vs. Apo-D negative: 33%, p =
      0.02) influenced the 5-year EFS, whereas sex, use of RT or number of previous
      surgical treatments did not. CONCLUSIONS: Patients with DFSP have a high survival
      probability. Site, adequate surgical margins, presence of the fibrosarcomatous
      component, lack of CD34 expression and apolipoprotein-D influence outcome.

PMID- 22587824
TI  - A tetracycline inducible expression vector for Corynebacterium glutamicum
      allowing tightly regulable gene expression.
AB  - Here we report on the construction of a tetracycline inducible expression vector
      that allows a tightly regulable gene expression in Corynebacterium glutamicum
      which is used in industry for production of small molecules such as amino acids.
      Using the green fluorescent protein (GFP) as a reporter protein we show that this
      vector, named pCLTON1, is characterized by tight repression under non-induced
      conditions as compared to a conventional IPTG inducible expression vector, and
      that it allows gradual GFP synthesis upon gradual increase of anhydrotetracycline
      addition.

PMID- 22587825
TI  - Genetic relationships among 527 Gram-negative bacterial plasmids.
AB  - Plasmids are mosaic in composition with a maintenance "backbone" as well as
      "accessory" genes obtained via horizontal gene transfer. This horizontal gene
      transfer complicates the study of their genetic relationships. We describe a
      method for relating a large number of Gram-negative (GN) bacterial plasmids based
      on their genetic sequences. Complete coding gene sequences of 527 GN bacterial
      plasmids were obtained from NCBI. Initial classification of their genetic
      relationships was accomplished using a computational approach analogous to
      hybridization of "mixed-genome microarrays." Because of this similarity, the
      phrase "virtual hybridization" is used to describe this approach. Protein
      sequences generated from the gene sequences were randomly chosen to serve as
      "probes" for the virtual arrays, and virtual hybridization for each GN plasmid
      was achieved using BLASTp. Each resulting intensity matrix was used to generate a
      distance matrix from which an initial tree was constructed. Relationships were
      refined for several clusters by identifying conserved proteins within a cluster.
      Multiple-sequence alignment was applied to the concatenated conserved proteins,
      and maximum likelihood was used to generate relationships from the results of the
      alignment. While it is not possible to prove that the genetic relationships among
      the 527 GN bacterial plasmids obtained in this study are correct, replication of
      identical results produced in a separate study for a small group of IncA/C
      plasmids provides evidence that the approach used can correctly predict genetic
      relationships. In addition, results obtained for clusters of Borrelia plasmids
      are consistent with the expected exclusivity for plasmids from this genus.
      Finally, the 527-plasmid tree was used to study the distribution of four common
      antibiotic resistance genes.

PMID- 22587826
TI  - The importance of metagenomic surveys to microbial ecology: or why Darwin would
      have been a metagenomic scientist.
AB  - Scientific discovery is incremental. The Merriam-Webster definition of
      'Scientific Method' is "principles and procedures for the systematic pursuit of
      knowledge involving the recognition and formulation of a problem, the collection
      of data through observation and experiment, and the formulation and testing of
      hypotheses". Scientists are taught to be excellent observers, as observations
      create questions, which in turn generate hypotheses. After centuries of science
      we tend to assume that we have enough observations to drive science, and enable
      the small steps and giant leaps which lead to theories and subsequent testable
      hypotheses. One excellent example of this is Charles Darwin's Voyage of the
      Beagle, which was essentially an opportunistic survey of biodiversity. Today,
      obtaining funding for even small-scale surveys of life on Earth is difficult; but
      few argue the importance of the theory that was generated by Darwin from his
      observations made during this epic journey. However, these observations, even
      combined with the parallel work of Alfred Russell Wallace at around the same time
      have still not generated an indisputable 'law of biology'. The fact that
      evolution remains a 'theory', at least to the general public, suggests that
      surveys for new data need to be taken to a new level.

PMID- 22587827
TI  - The UK Responsibility Deal and its implications for effective alcohol policy in
      the UK and internationally.

PMID- 22587828
TI  - Early course of microcirculatory perfusion in eye and digestive tract during
      hypodynamic sepsis.
AB  - INTRODUCTION: The aim of the study was to evaluate and compare the
      microcirculatory perfusion during experimental sepsis in different potentially
      available parts of the body, such as sublingual mucosa, conjunctiva of the eye,
      and mucosa of jejunum and rectum. METHODS: Pigs were randomly assigned to sepsis
      (n = 9) and sham (n = 4) groups. The sepsis group received a fixed dose of live
      Escherichia coli infusion over a 1-hour period (1.8 * 10(9)/kg colony-forming
      units). Animals were observed 5 hours after the start of E. coli infusion. In
      addition to systemic hemodynamic assessment, we performed conjunctival,
      sublingual, jejunal, and rectal evaluation of microcirculation by using
      Sidestream Dark Field (SDF) videomicroscopy at the same time points: at baseline,
      and at 3 and 5 hours after the start of live E. coli infusion. Assessment of
      microcirculatory parameters of convective oxygen transport (microvascular flow
      index (MFI) and proportion of perfused vessels (PPV)), and diffusion distance
      (perfused vessel density (PVD) and total vessel density (TVD)) was done by using
      a semiquantitative method. RESULTS: Infusion of E. coli resulted in a hypodynamic
      state of sepsis associated with low cardiac output and increased systemic
      vascular resistance despite fluid administration. Significant decreases in MFI
      and PPV of small vessels were observed in sublingual, conjunctival, jejunal, and
      rectal locations 3 and 5 hours after the start of E. coli infusion in comparison
      with baseline variables. Correlation between sublingual and conjunctival (r =
      0.80; P = 0.036), sublingual and jejunal (r = 0.80; P = 0.044), and sublingual
      and rectal (r = 0.79; P = 0.03) MFI was observed 3 hours after onset of sepsis.
      However, this strong correlation between the sublingual and other regions
      disappeared 5 hours after the start of E. coli infusion. Overall, the sublingual
      mucosa exhibited the most-pronounced alterations of microcirculatory flow in
      comparison with conjunctival, jejunal, and rectal microvasculature (P < 0.05).
      CONCLUSIONS: In this pig model, a time-dependent correlation exists between
      sublingual and microvascular beds during the course of a hypodynamic state of
      sepsis.

PMID- 22587829
TI  - Routine development of objectively derived search strategies.
AB  - BACKGROUND: Over the past few years, information retrieval has become more and
      more professionalized, and information specialists are considered full members of
      a research team conducting systematic reviews. Research groups preparing
      systematic reviews and clinical practice guidelines have been the driving force
      in the development of search strategies, but open questions remain regarding the
      transparency of the development process and the available resources. An
      empirically guided approach to the development of a search strategy provides a
      way to increase transparency and efficiency. METHODS: Our aim in this paper is to
      describe the empirically guided development process for search strategies as
      applied by the German Institute for Quality and Efficiency in Health Care
      (Institut fur Qualitat und Wirtschaftlichkeit im Gesundheitswesen, or "IQWiG").
      This strategy consists of the following steps: generation of a test set, as well
      as the development, validation and standardized documentation of the search
      strategy. RESULTS: We illustrate our approach by means of an example, that is, a
      search for literature on brachytherapy in patients with prostate cancer. For this
      purpose, a test set was generated, including a total of 38 references from 3
      systematic reviews. The development set for the generation of the strategy
      included 25 references. After application of textual analytic procedures, a
      strategy was developed that included all references in the development set. To
      test the search strategy on an independent set of references, the remaining 13
      references in the test set (the validation set) were used. The validation set was
      also completely identified. DISCUSSION: Our conclusion is that an objectively
      derived approach similar to that used in search filter development is a feasible
      way to develop and validate reliable search strategies. Besides creating high
      quality strategies, the widespread application of this approach will result in a
      substantial increase in the transparency of the development process of search
      strategies.

PMID- 22587830
TI  - The great Indian invisible railroad disaster.

PMID- 22587831
TI  - BClI polymorphism of the glucocorticoid receptor gene is associated with
      increased obesity, impaired glucose metabolism and dyslipidaemia in patients with
      Addison's disease.
AB  - OBJECT: Although glucocorticoids are essential for health, several studies have
      shown that glucocorticoids replacement in Addison's disease might be involved in
      anthropometric and metabolic impairment, with increased cardiovascular risk,
      namely if conventional doses are used. As the effects of glucocorticoids are
      mediated by the glucocorticoid receptor, encoded by NR3C1 gene, different
      polymorphisms in the NR3C1 gene have been linked to altered glucocorticoid
      sensitivity in general population as well as in patients with obesity or
      metabolic syndrome. DESIGN: We investigated the impact of glucocorticoid receptor
      gene polymorphisms, including the BclI, N363S and ER22/23EK variants, on
      anthropometric parameters (BMI and waist circumference), metabolic profile (HOMA,
      OGTT and serum lipids) and ACTH levels in 50 patients with Addison's disease (34
      women and 16 men, age 20-82 year) under glucocorticoids replacement. RESULTS:
      Neither N363S nor ER22/23EK variants were significantly associated with
      anthropometric, metabolic or hormonal parameters, while patients carrying the
      homozygous BclI polymorphism GG (n = 4) showed higher (P < 0.05) BMI, waist
      circumference, HOMA and 2-h glucose levels after OGTT, as well as total
      cholesterol and triglycerides than those with wild-type genotype CC (n = 28) or
      heterozygous CG (n = 18). The totality of GG patients was connoted by abdominal
      adiposity, impaired glucose tolerance/diabetes mellitus or dyslipidaemia, while a
      lower percentage of CC or CG patients showed some anthropometric and metabolic
      alterations. CONCLUSION: These results suggest that BclI polymorphism may
      influence the sensitivity to glucocorticoids in patients with Addison's disease
      and may contribute, along with other factors, to the increase in central
      adiposity, impaired glucose metabolism and dyslipidaemia.

PMID- 22587832
TI  - "Military importance": what does it mean and can it be assessed objectively?

PMID- 22587833
TI  - Absolute and relative morbidity burdens attributable to various illnesses and
      injuries, U.S. Armed Forces, 2011.

PMID- 22587835
TI  - Ambulatory visits among members of the active component, U.S. Armed Forces, 2011.

PMID- 22587834
TI  - Hospitalizations among members of the active component, U.S. Armed Forces, 2011.

PMID- 22587837
TI  - Anti-amyloidogenic effects of soybean isoflavones in vitro: Fluorescence
      spectroscopy demonstrating direct binding to Abeta monomers, oligomers and
      fibrils.
AB  - Alzheimer's disease is characterized by the presence of extracellular deposits of
      amyloid, primarily composed of the amyloid beta-protein (Abeta). A growing body
      of evidence indicates that oligomeric forms of Abeta play a critical role in
      disease causation. Soybean isoflavones are flavonoids with an isoflavone
      backbone. Isoflavones have been reported to protect against Abeta-induced
      neurotoxicity in cultured cell systems, the molecular mechanisms remain unclear.
      Our previous studies demonstrated that red wine-related flavonoids with a flavone
      backbone are able to inhibit Abeta assembly and destabilize preformed Abeta
      aggregates. Here, we show that isoflavones, especially glycitein and genistein,
      have anti-fibrillization, anti-oligomerization and fibril-destabilizing effects
      on Abeta(1-40) and Abeta(1-42)in vitro at physiological pH and temperature, by
      using nucleation-dependent polymerization monitored by thioflavin T fluorescence,
      atomic force microscopy, electron microscopy, and photo-induced cross-linking of
      unmodified proteins followed by SDS-PAGE. Our three-dimensional fluorescence
      spectroscopic analyses demonstrated that glycitein interacted with Abeta
      monomers, oligomers and fibrils, indicating specific binding of glycitein to
      these Abeta species. Glycitein also interacted with different Abeta fragments
      (Abeta(1-42), Abeta(1-40), Abeta(1-16) and Abeta(25-35)), exhibiting the highest
      fluorescence enhancement with Abeta(25-35). We speculated that glycitein's anti
      amyloidogenic properties are specifically mediated by its binding to Abeta
      monomers, oligomers and fibrils. Isoflavones may hold promise as a treatment
      option for preventative strategies targeting amyloid formation in Alzheimer's
      disease.

PMID- 22587838
TI  - HSF4 is involved in DNA damage repair through regulation of Rad51.
AB  - Heat shock factor protein 4 (HSF4) is expressed exclusively in the ocular lens
      and plays a critical role in the lens formation and differentiation. Mutations in
      the HSF4 gene lead to congenital and senile cataract. However, the molecular
      mechanisms causing this disease have not been well characterized. DNA damage in
      lens is a crucial risk factor in senile cataract formation, and its timely repair
      is essential for maintaining the lens' transparency. Our study firstly found
      evidence that HSF4 contributes to the repair of DNA strand breaks. Yet, this does
      not occur with cataract causative mutations in HSF4. We verify that DNA damage
      repair is mediated by the binding of HSF4 to a heat shock element in the Rad51
      promoter, a gene which assists in the homologous recombination (HR) repair of DNA
      strand breaks. HSF4 up-regulates Rad51 expression while mutations in HSF4 fail,
      and DNA does not get repaired. Camptothecin, which interrupts the regulation of
      Rad51 by HSF4, also affects DNA damage repair. Additionally, with HSF4 knockdown
      in the lens of Zebrafish, DNA damage was observed and the protein level of Rad51
      was significantly lower. Our study presents the first evidence demonstrating that
      HSF4 plays a role in DNA damage repair and may contribute a better understanding
      of congenital cataract formation.

PMID- 22587842
TI  - The nuts and bolts of PROSPERO: an international prospective register of
      systematic reviews.
AB  - BACKGROUND: Following publication of the PRISMA statement, the UK Centre for
      Reviews and Dissemination (CRD) at the University of York in England began to
      develop an international prospective register of systematic reviews with health
      related outcomes. The objectives were to reduce unplanned duplication of reviews
      and provide transparency in the review process, with the aim of minimizing
      reporting bias. METHODS: An international advisory group was formed and a
      consultation undertaken to establish the key items necessary for inclusion in the
      register and to gather views on various aspects of functionality. This article
      describes the development of the register, now called PROSPERO, and the process
      of registration. RESULTS: PROSPERO offers free registration and free public
      access to a unique prospective register of systematic reviews across all areas of
      health from all around the world. The dedicated web-based interface is
      electronically searchable and available to all prospective registrants. At the
      moment, inclusion in PROSPERO is restricted to systematic reviews of the effects
      of interventions and strategies to prevent, diagnose, treat, and monitor health
      conditions, for which there is a health-related outcome.Ideally, registration
      should take place before the researchers have started formal screening against
      inclusion criteria but reviews are eligible as long as they have not progressed
      beyond the point of completing data extraction.The required dataset captures the
      key attributes of review design as well as the administrative details necessary
      for registration.Submitted registration forms are checked against the scope for
      inclusion in PROSPERO and for clarity of content before being made publicly
      available on the register, rejected, or returned to the applicant for
      clarification.The public records include an audit trail of major changes to
      planned methods, details of when the review has been completed, and links to
      resulting publications when provided by the authors. CONCLUSIONS: There has been
      international support and an enthusiastic response to the principle of
      prospective registration of protocols for systematic reviews and to the
      development of PROSPERO.In October 2011, PROSPERO contained 200 records of
      systematic reviews being undertaken in 26 countries around the world on a diverse
      range of interventions.

PMID- 22587841
TI  - Comprehensive analysis of published phase I/II clinical trials between 1990-2010
      in osteosarcoma and Ewing sarcoma confirms limited outcomes and need for
      translational investment.
AB  - BACKGROUND: High grade primary bone sarcomas are rare cancers that affect mostly
      children and young adults. Osteosarcoma and Ewing sarcoma are the most common
      histological subtypes in this age group, with current multimodality treatment
      strategies achieving 55-70% overall survival. As there remains an urgent need to
      develop new therapeutic interventions, we have reviewed published phase I/II
      trials that have been reported for osteosarcoma and Ewing sarcoma in the last
      twenty years. RESULTS: We conducted a literature search for clinical trials
      between 1990 and 2010, either for trials enrolling bone sarcoma patients as part
      of a general sarcoma indication or trials specifically in osteosarcoma and Ewing
      sarcoma. We identified 42 clinical trials that fulfilled our search criteria for
      general sarcoma that enrolled these patient groups, and eight and twenty specific
      trials for Ewing and osteosarcoma patients, respectively. For the phase I trials
      which enrolled different tumour types our results were incomplete, because the
      sarcoma patients were not mentioned in the PubMed abstract. A total of 3,736
      sarcoma patients were included in these trials over this period, 1,114 for
      osteosarcoma and 1,263 for Ewing sarcoma. As a proportion of the worldwide
      disease burden over this period, these numbers reflect a very small percentage of
      the potential patient recruitment, approximately 0.6% for Ewing sarcoma and 0.2%
      for osteosarcoma. However, these data show an increase in recent activity overall
      and suggest there is still much room for improvement in the current trial
      development structures. CONCLUSION: Lack of resources and commercial investment
      will inevitably limit opportunity to develop sufficiently rapid improvements in
      clinical outcomes. International collaboration exists in many well founded co
      operative groups for phase III trials, but progress may be more effective if
      there were also more investment of molecular and translational research into
      disease focused phase I/II clinical trials. Examples of new models for early
      translational and early phase trial collaboration include the European based
      EuroBoNeT network, the Sarcoma Alliance for Research through Collaboration
      network (SARC) and the new European collaborative translational trial network,
      EuroSarc.

PMID- 22587843
TI  - Geographic variation in corticosterone response to chronic predator stress in
      tadpoles.
AB  - Chronic stress often affects growth and development negatively, and these effects
      are often mediated via glucocorticoid hormones, which elevate during stress. We
      investigated latitudinal variation in corticosterone (CORT) response to chronic
      predator stress in Rana temporaria tadpoles along a 1500-km latitudinal cline in
      Sweden tadpoles, in a laboratory experiment. We hypothesized that more time
      constrained high-latitude populations have evolved a lower CORT response to
      chronic stress to maintain higher growth under stressful conditions. Southern
      tadpoles had higher CORT content in response to predators after 1 day of
      exposure, whereas there was no increase in CORT in the northern populations. Two
      weeks later, there were no predator-induced CORT elevations. Artificially
      elevated CORT levels strongly decreased growth, development and survival in both
      northern and southern tadpoles. We suggest that the lower CORT response in high
      latitude populations can be connected with avoidance of CORT-mediated reduction
      in growth and development, but also discuss other possible explanations.

PMID- 22587844
TI  - Plasticity and heritability of morphological variation within and between
      parapatric stickleback demes.
AB  - The threespine stickleback (Gasterosteus aculeatus) has emerged as an important
      model organism in evolutionary ecology, largely due to the repeated, parallel
      evolution of divergent morphotypes found in populations having colonized
      freshwater habitats. However, morphological divergence following colonization is
      not a universal phenomenon. We explore this in a large-scale estuarine ecosystem
      inhabited by two parapatric stickleback demes, each physiologically adapted to
      divergent osmoregulatory environments (fresh vs. saline waters). Using geometric
      morphometric analyses of wild-caught individuals, we detected significant
      differences between demes, in addition to sexual dimorphism, in body shape.
      However, rearing full-sib families from each deme under controlled, reciprocal
      salinity conditions revealed no differences between genotypes and highly
      significant environmental effects. It is also noteworthy that fish from both
      demes were fully plated, whether found in the wild or reared under reciprocal
      salinity conditions. Although we found significant heritability for body shape,
      we also noted significant direct environmental effects for many latent shape
      variables. Moreover, we found little evidence for diversifying selection acting
      on body size and shape (Q(ST) ). Nevertheless, uniform compressive variation did
      exceed neutral expectations, yet despite evidence of both allometry and genetic
      correlation with body length, we detected no correlated signatures of selection.
      Taken together, these results suggest that much of the morphological divergence
      observed in this system is the result of plastic responses to environmental
      variation rather than adaptive differentiation.

PMID- 22587845
TI  - Use it or lose it: reproductive implications of ecological specialization in a
      haematophagous ectoparasite.
AB  - Using experimentally induced disruptive selection, we tested two hypotheses
      regarding the evolution of specialization in parasites. The 'trade-off'
      hypothesis suggests that adaptation to a specific host may come at the expense of
      a reduced performance when exploiting another host. The alternative 'relaxed
      selection' hypothesis suggests that the ability to exploit a given host would
      deteriorate when becoming obsolete. Three replicate populations of a flea
      Xenopsylla ramesis were maintained on each of two rodent hosts, Meriones crassus
      and Dipodillus dasyurus, for nine generations. Fleas maintained on a specific
      host species for a few generations substantially decreased their reproductive
      performance when transferred to an alternative host species, whereas they
      generally did not increase their performance on their maintenance host. The
      results support the 'relaxed selection' hypothesis of the evolution of ecological
      specialization in haematophagous ectoparasites, while suggesting that trade-offs
      are unlikely drivers of specialization. Further work is needed to study the
      extent by which the observed specializations are based on epigenetic or genetic
      modifications.

PMID- 22587846
TI  - Decontamination of human and rabbit skin experimentally contaminated with 99mTc
      radionuclide using the active components of "Shudhika"-a skin decontamination
      kit.
AB  - INTRODUCTION: Radioactive contamination can occur as a result of accidental or
      intentional release of radioactive materials (RM) into the environment. RM may
      deposit on clothing, skin, or hair. Decontamination of contaminated persons
      should be done as soon as possible to minimize the deleterious health effects of
      radiation. The goal of this study was to evaluate the decontamination efficiency
      (for residual contaminant) of the active components of "Shudhika," an
      indigenously developed skin decontamination kit. The study kit is for external
      radioactive decontamination of intact skin. METHODS: Decontamination efficiency
      was evaluated on the skin surface of rabbit (n = 6) and human volunteers (n =
      13). 99mTc sodium pertechnetate (200-250 MUCi) was used as the radio-contaminant.
      Skin surface area (5 * 5 cm2) of thoracic abdominal region of the rabbit and the
      forearm and the palm of human volunteers were used for the study. Decontamination
      was performed by using cotton swabs soaked with chemical decontamination agents
      of the kit. RESULTS: Decontamination efficiency (% of the contaminant removed)
      was calculated for each component of the study. Overall effectiveness of the kit
      was calculated to be 85% +/- 5% in animal and 92% +/- 3% in human skin surfaces.
      Running water and liquid soap with water was able to decontaminate volunteers'
      hand and animal skin up to 70% +/- 5%. Chemical decontamination agents were
      applied only for trace residues (30% +/- 5%). Efficiency of all the kit
      components was found up to be 20% +/- 3% (animal) and 28% +/- 2 (human),
      respectively. Residual contamination after final decontamination attempt for both
      the models was observed to be 12% +/- 3% and 5% +/- 2%. After 24 and 48 hours of
      the decontamination procedure, skin was found to be normal (no redness, erythema
      and edema were observed). CONCLUSION: Decontaminants of the study kit were
      effective in removal of localized radioactive skin contamination when water is
      ineffective for further decontamination. By using the chemical decontaminants of
      the study kit, the use of water and radioactive waste generation could be
      reduced. Cross-contamination could also be avoided. During radiologic emergencies
      where water may be radioactively contaminated, the study kit could be used.

PMID- 22587847
TI  - Large-scale experimental studies show unexpected amino acid effects on protein
      expression and solubility in vivo in E. coli.
AB  - The biochemical and physical factors controlling protein expression level and
      solubility in vivo remain incompletely characterized. To gain insight into the
      primary sequence features influencing these outcomes, we performed statistical
      analyses of results from the high-throughput protein-production pipeline of the
      Northeast Structural Genomics Consortium. Proteins expressed in E. coli and
      consistently purified were scored independently for expression and solubility
      levels. These parameters nonetheless show a very strong positive correlation. We
      used logistic regressions to determine whether they are systematically influenced
      by fractional amino acid composition or several bulk sequence parameters
      including hydrophobicity, sidechain entropy, electrostatic charge, and predicted
      backbone disorder. Decreasing hydrophobicity correlates with higher expression
      and solubility levels, but this correlation apparently derives solely from the
      beneficial effect of three charged amino acids, at least for bacterial proteins.
      In fact, the three most hydrophobic residues showed very different correlations
      with solubility level. Leu showed the strongest negative correlation among amino
      acids, while Ile showed a slightly positive correlation in most data segments.
      Several other amino acids also had unexpected effects. Notably, Arg correlated
      with decreased expression and, most surprisingly, solubility of bacterial
      proteins, an effect only partially attributable to rare codons. However, rare
      codons did significantly reduce expression despite use of a codon-enhanced
      strain. Additional analyses suggest that positively but not negatively charged
      amino acids may reduce translation efficiency in E. coli irrespective of codon
      usage. While some observed effects may reflect indirect evolutionary
      correlations, others may reflect basic physicochemical phenomena. We used these
      results to construct and validate predictors of expression and solubility levels
      and overall protein usability, and we propose new strategies to be explored for
      engineering improved protein expression and solubility.

PMID- 22587848
TI  - Iodine deficiency in pregnant women in the apparently iodine-sufficient capital
      city of Turkey.
AB  - OBJECTIVE: Previous studies of the current iodine status in Turkey have yielded
      contradictory results. Although urinary iodine concentration (UIC) in school age
      children (SAC) suggests sufficient iodine status, studies on neonatal thyroid
      stimulating hormone (TSH) indicate that iodine deficiency is a continuing
      problem. We aimed to assess the iodine nutritional status of pregnant women
      living in Ankara, an area that has appeared to be iodine sufficient in earlier
      studies. DESIGN: Hospital-based, noninterventional, prospective, cross-sectional
      study. METHODS: A total of 162 pregnant women in their second trimester were
      examined regarding iodized salt use, UIC, presence or absence of goitre and
      thyroid function. Goitre status was determined by palpation. UIC was measured
      using colorimetric method based on Sandell-Kolthoff reaction. Thyroid hormones
      and TSH were measured by chemiluminescence immunoassays. RESULTS: While the
      proportion of iodized salt use was 80.2%, UIC was below 150 MUg/l in 72.8% of the
      women. The median UIC was 80.5 (8.9-340.3) MUg/l, indicating insufficient iodine
      intake. Total goitre rate was 15.4%. Preferential T3 secretion reflected by
      elevated molar ratios of FT3/FT4 was present in 89.5% of the women. 12.4% had
      subclinical hypothyroidism or isolated hypothyroxinaemia based on serum TSH and
      FT4 levels. CONCLUSIONS: Our study shows that iodine deficiency is a serious
      problem among pregnant women in Ankara. These data confirm that iodine
      nutritional status among SAC does not reflect the iodine supply for pregnant
      women. We propose that nationwide surveillance studies should urgently be
      performed to directly assess and monitor the iodine status of pregnant women. We
      also consider that pregnant women in Turkey should be supplemented by iodine
      containing preparations in addition to iodized salt.

PMID- 22587850
TI  - Effectiveness of tai chi as a community-based falls prevention intervention: a
      randomized controlled trial.
AB  - OBJECTIVES: To compare the effectiveness of tai chi and low-level exercise in
      reducing falls in older adults; to determine whether mobility, balance, and lower
      limb strength improved and whether higher doses of tai chi resulted in greater
      effect. DESIGN: Randomized controlled trial. SETTING: Eleven sites throughout New
      Zealand. PARTICIPANTS: Six hundred eighty-four community-residing older adults
      (mean age 74.5; 73% female) with at least one falls risk factor. INTERVENTION:
      Tai chi once a week (TC1) (n = 233); tai chi twice a week (TC2) (n = 220), or a
      low-level exercise program control group (LLE) (n = 231) for 20 wks.
      MEASUREMENTS: Number of falls was ascertained according to monthly falls
      calendars. Mobility (Timed-Up-and-Go Test), balance (step test), and lower limb
      strength (chair stand test) were assessed. RESULTS: The adjusted incident rate
      ratio (IRR) for falls was not significantly different between the TC1 and LLE
      groups (IRR = 1.05, 95% confidence interval (CI) = 0.83-1.33, P = .70) or between
      the TC2 and LLE groups (IRR = 0.88, 95% CI = 0.68-1.16, P = .37). Adjusted
      multilevel mixed-effects Poisson regression showed a significant reduction in
      logarithmic mean fall rate of -0.050 (95% CI = -0.064 to -0.037, P < .001) per
      month for all groups. Multilevel fixed-effects analyses indicated improvements in
      balance (P < .001 right and left leg) and lower limb strength (P < .001) but not
      mobility (P = .54) in all groups over time, with no differences between the
      groups (P = .37 (right leg), P = .66 (left leg), P = .21, and P = .44,
      respectively). CONCLUSION: There was no difference in falls rates between the
      groups, with falls reducing similarly (mean falls rate reduction of 58%) over the
      17-month follow-up period. Strength and balance improved similarly in all groups
      over time.

PMID- 22587849
TI  - Transitions in care for older adults with and without dementia.
AB  - OBJECTIVES: To describe transitions in care of persons with dementia with
      attention to nursing facility transitions. DESIGN: Prospective cohort. SETTING:
      Public health system. PARTICIPANTS: Four thousand one hundred ninety-seven
      community-dwelling older adults. MEASUREMENTS: Participants' electronic medical
      records were merged with Medicare claims, Medicaid claims, the Minimum Data Set
      (MDS), and the Outcome and Assessment Information Set (OASIS) from 2001 to 2008
      with a mean follow-up of 5.2 years from the time of enrollment. RESULTS: Older
      adults with prevalent (n = 524) or incident (n = 999) dementia had greater
      Medicare (44.7% vs 44.8% vs 11.4%, P < .001) and Medicaid (21.0% vs 16.8% vs
      1.4%, P < .001) nursing facility use, greater hospital (76.2% vs 86.0% vs 51.2%,
      P < .001) and home health (55.7% vs 65.2% vs 27.3%, P < .001) use, more
      transitions in care per person-year of follow-up (2.6 vs 2.7 vs 1.4, P < .001),
      and more mean total transitions (11.2 vs 9.2 vs 3.8, P < .001) than those who
      were never diagnosed (n = 2,674). For the 1,523 participants with dementia, 74.5%
      of transitions to nursing facilities were transfers from hospitals. For
      transitions from nursing facilities, the conditional probability was 41.0% for a
      return home without home health care, 10.7% for home health care, and 39.8% for a
      hospital transfer. Of participants with dementia with a rehospitalization within
      30 days, 45% had been discharged to nursing facilities from the index
      hospitalization. At time of death, 46% of participants with dementia were at
      home, 35% were in the hospital, and 19% were in a nursing facility. CONCLUSION:
      Individuals with dementia live and frequently die in community settings. Nursing
      facilities are part of a dynamic network of care characterized by frequent
      transitions.

PMID- 22587851
TI  - Fruit and vegetable intake, physical activity, and mortality in older community
      dwelling women.
AB  - OBJECTIVES: To examine the relationship between fruit and vegetable intake,
      physical activity, and all-cause mortality in older women. DESIGN: Six Cox
      proportional hazards models examined independent and additive relationships
      between physical activity, carotenoids, and all-cause mortality. Additional
      models tested whether physical activity and carotenoids were conjointly related
      to mortality. Models were adjusted for age, education, and race and ethnicity.
      SETTING: Baltimore, Maryland. PARTICIPANTS: Seven hundred thirteen women aged 70
      to 79 participating in the Women's Health and Aging Studies. MEASUREMENTS: Total
      serum carotenoids, a marker of fruit and vegetable intake, and physical activity
      were measured at baseline. Physical activity was measured according to
      kilocalorie expenditure. RESULTS: During 5 years of follow-up, 82 (11.5%)
      participants died. Measured continuously, physical activity improved survival (HR
      = 0.52, 95% CI = 0.41-0.66, P < .001). The most active women were more likely to
      survive than the least physically active women (HR = 0.28, 95% CI = 0.13-0.59, P
      < .001). Continuous measures of carotenoids improved survival (HR = 0.67, 95% CI
      = 0.51-0.89, P = .01). Women in the highest tertile of total carotenoids were
      more likely to survive those in the lowest (HR = 0.50, 95% CI = 0.27-0.91, P =
      .03). When examined in the same model, continuous measures of physical activity
      (HR = 0.54, 95% CI = 0.42-0.68, P < .001) and carotenoids (HR = 0.76, 95% CI =
      0.59-0.98, P = .04) predicted survival during follow-up. CONCLUSION: The
      combination of low total serum carotenoids and low physical activity, both
      modifiable risk factors, strongly predicted earlier mortality. These findings
      provide preliminary support that higher fruit and vegetable intake and exercise
      improve survival.

PMID- 22587852
TI  - Are geriatricians more efficient than other physicians at managing inpatient care
      for elderly patients?
AB  - OBJECTIVES: To compare outcomes and measures of efficiency for hospitalized
      elderly adults managed by geriatricians with those managed by other physicians.
      DESIGN: Secondary data analysis using a system that integrates clinical and
      financial information for inpatient and outpatient services delivered throughout
      the University of Pittsburgh Medical Center (UPMC). Propensity scores were
      developed based on participant sociodemographic and clinical characteristics and
      used to match participants based on the attending physician's specialty
      (geriatrician, n = 701; nongeriatrician, n = 11,549). Multivariate analyses using
      generalized estimating equations methods were performed. SETTING: Two UPMC
      hospitals in Pittsburgh, Pennsylvania. PARTICIPANTS: Patients aged 65 and older
      admitted in 2002 in a medical diagnosis-related group (DRG). MEASUREMENTS:
      Outcomes (inpatient mortality, 30-day mortality, readmission) and efficiency
      measures (length of stay, total costs, and surplus, which is the difference
      between hospital costs and payment received for an admission). RESULTS: Elderly
      adults managed by geriatricians were significantly older (P < .001) and more
      likely to be male (P < .001) and had more diagnoses (P < .001). Propensity scores
      successfully balanced characteristics managed by the two groups. Patients of
      geriatricians had shorter length of stay (P < .001), lower costs per admission (P
      < .001), and greater surplus (P < .001) with no differences in outcomes. In
      multivariate analyses, there were not significant differences in outcomes, but
      patients of geriatricians had significantly shorter length of stay and lower
      costs per admission and generated more surplus for the hospitals. CONCLUSION:
      Geriatricians were more efficient than other physicians in managing hospitalized
      elderly adults with medical DRGs frequently managed by geriatricians. This
      efficiency did not compromise patient outcomes.

PMID- 22587853
TI  - Underuse of diagnostic codes for specific dementias in the Veterans Affairs New
      England healthcare system.
AB  - OBJECTIVES: To examine the specificity of dementia coding in large populations.
      DESIGN: Retrospective cohort and chart review study of dementia diagnosis.
      SETTING: U.S. Department of Veterans Affairs (VA) New England healthcare system.
      PARTICIPANTS: Veterans aged 50 and older given outpatient visit codes for
      dementia between January 1, 2000, and December 31, 2009. MEASUREMENTS: The
      frequency of the code "dementia not otherwise specified (DNOS)" as a first and
      final diagnosis was determined. DNOS use was examined according to provider type
      and geographic location. The medical records of 100 individuals with unspecified
      dementia were reviewed to determine their underlying diagnoses and describe their
      examination. RESULTS: Twenty-two thousand fifty veterans diagnosed with dementia
      were identified over 10 years of follow-up. One-third of all cases had no
      specific dementia code (n = 6,659). DNOS was the most commonly used code as a
      first dementia diagnosis (42.5%) and was second only to Alzheimer's type dementia
      (35.8%) as a final diagnosis. Individuals who saw geriatricians and neurologists
      were most likely to have a specific dementia diagnosis, and DNOS use was lowest
      in centers with the most dementia specialists. Only 12% of primary care
      physicians performed cognitive testing the first time they used the DNOS code,
      compared with 98% of specialists. Nearly half of individuals with a persistent
      diagnosis of DNOS met criteria for a specific dementia. CONCLUSION: Substantial
      overuse was found of nonspecific dementia codes in the VA New England healthcare
      system, leading to an underestimation of the prevalence of Alzheimer's disease
      and other dementias. System-based changes in dementia coding and greater access
      to dementia specialists may help improve diagnostic specificity.

PMID- 22587854
TI  - Racial differences in gait velocity in an urban elderly cohort.
AB  - OBJECTIVES: To investigate whether there are racial differences in gait velocity
      in elderly adults. DESIGN: Cross-sectional analysis. SETTING: Bronx, New York.
      PARTICIPANTS: Two hundred thirteen participants of the Einstein Aging Study (157
      Caucasian, 56 African American), a longitudinal study of community-residing
      elderly adults recruited using Medicare and voter registration records.
      MEASUREMENTS: Demographic characteristics, medical history, Geriatric Depression
      Scale, Blessed Information-Memory-Concentration Test, Total Pain Index, gait
      velocity. RESULTS: Caucasians were older (median 79.9 vs 75.5, P = .002) and more
      educated (median 14 vs 12 years, P = .007) and had lower body mass index (mean
      26.9 +/- 4.3 vs 28.9 +/- 6.4, P = .03). African Americans were more likely to be
      female (80.4% vs 59.9%, P = .006) and to have diabetes mellitus (28.6% vs 13.4%,
      P = .01). Pain levels were not significantly different between Caucasians and
      African Americans. African Americans had a significantly slower gait velocity
      (mean 90.2 +/- 17.9 vs 99.1 +/- 20.1 cm/s, P = .004). This difference persisted
      after adjusting for multiple covariates. Differences in common factors known to
      influence gait did not explain a 7.79-cm/s slower gait speed in African Americans
      than Caucasians. CONCLUSION: Differences in gait velocity persist between African
      Americans and Caucasians despite adjusting for many confounders. Increases of
      just 10 cm/s are associated with lower mortality. Further studies are needed to
      evaluate whether there are modifiable risk factors that may explain this
      difference and whether an intervention could reduce the discrepancy between the
      groups.

PMID- 22587855
TI  - Insufficient help for activity of daily living disabilities and risk of all-cause
      hospitalization.
AB  - OBJECTIVES: To determine whether insufficient help for activity of daily living
      (ADL) disability, a potentially modifiable condition, significantly increases
      disabled older adults' risk of future hospital admissions. DESIGN: Prospective
      study. SETTING: Community-living participants with ADL disabilities in the 1994,
      1999, and 2004 National Long-Term Care Survey (NLTCS). PARTICIPANTS: Medicare
      recipients with one or more ADL disabilities completed 5,884 surveys.
      MEASUREMENTS: Times to hospital admission in the year after the NLTCS community
      survey were obtained from linked Medicare claims. Insufficient ADL help for each
      ADL limitation was determined from a series of questions common to the three
      NLTCS community surveys. RESULTS: Insufficient help for one or more ADL
      limitations was reported in 22% of surveys. Respondents to 3,629 surveys did not
      experience a hospital admission in the year after the survey. Of the remaining
      2,255 surveys, one admission occurred for 382 surveys, two admissions for 525
      surveys, three admissions for 193 surveys, and four or more admissions for 155
      surveys. Participants reporting insufficient help were 14% (hazard ratio = 1.14,
      95% confidence interval = 1.01-1.28) more likely to experience one or more
      hospitalizations than those who did not report insufficient help after
      controlling for demographic characteristics, comorbidities, prior
      hospitalizations, and level of ADL disability. CONCLUSION: Self-reports of
      insufficient help provide prognostic information beyond what typical health
      assessments can capture. Greater recognition and referral for insufficient help
      for ADL disability may result in lower rates of hospitalization in a population
      that is at high risk of hospitalization.

PMID- 22587856
TI  - Frailty and disability in older adults with intellectual disabilities: results
      from the healthy ageing and intellectual disability study.
AB  - OBJECTIVES: To obtain first insight into prevalence and correlates of frailty in
      older people with intellectual disability (ID). DESIGN: Population-based cross
      sectional study in persons using formal ID services. SETTING: Three Dutch care
      provider services. PARTICIPANTS: Eight hundred forty-eight individuals with
      borderline to profound ID aged 50 and older participating in the Healthy Ageing
      and Intellectual Disability (HA-ID) Study. MEASUREMENTS: All participants
      underwent an extensive health examination. Frailty was diagnosed according to
      Cardiovascular Health Study criteria. Associations between frailty and
      participant characteristics were investigated using multivariate logistic
      regression analysis. RESULTS: Prevalence of frailty was 11% at age 50 to 64 and
      18% at age 65 and older. Age, Down syndrome, dementia, motor disability, and
      severe ID were significantly associated with frailty, but only motor disability
      had a unique association with frailty. In a regression model with these
      variables, 25% of the variance of frailty was explained. CONCLUSION: At age 50 to
      64, prevalence of frailty is as high as in the general population aged 65 and
      older (7-9%), with a further increase after the age of 65. Motor disability only
      partially explains frailty. Future studies should address health outcomes,
      causes, and prevention of frailty in this population.

PMID- 22587858
TI  - Dementia as a moving target.

PMID- 22587857
TI  - Falls in newly admitted nursing home residents: a national study.
AB  - OBJECTIVES: To examine the relationship between nursing home (NH) organizational
      characteristics and falls in newly admitted NH residents. DESIGN: Observational
      cross-sectional study from January 1, 2006, to December 31, 2006. SETTING: NHs in
      the United States in 2006. PARTICIPANTS: Individuals (n = 230,730) admitted to a
      NH in 2006 without a prior NH stay and with a follow-up Minimum Data Set (MDS)
      assessment completed 30 days or more after admission. MEASUREMENTS: The
      relationship between experiencing a fall noted on the MDS assessment and NH
      characteristics (e.g., staffing, profit and chain status, religious affiliation,
      hospital-based facility status, number of beds, presence of a special care unit,
      funding) was examined, adjusting for NH resident characteristics. RESULTS: Twenty
      one percent of this cohort (n = 47,750) had experienced at least one fall in the
      NH at the time of the MDS assessment, which was completed for newly admitted NH
      residents who had at least a 30-day stay. NHs with higher certified nursing
      assistant (CNA) staffing had lower rates of falls (adjusted odds ratio = 0.97,
      95% confidence interval = 0.95-0.99). CONCLUSION: For newly admitted NH
      residents, NHs with higher CNA staffing had a lower fall rate. In an effort to
      maximize fall prevention efforts, further research is needed to understand the
      relationship between CNA staffing and falls in this NH population.

PMID- 22587859
TI  - Chorea in an 83-year-old woman: don't forget Huntington's disease.

PMID- 22587860
TI  - Fever of unknown origin in an elderly adult with lipid overload syndrome.

PMID- 22587861
TI  - Association between vitamin D3 supplementation and serum 25-hydroxyvitamin D
      levels in older individuals residing in long-term care in Ontario, Canada.

PMID- 22587862
TI  - Effect of a mobile safety alarm on going outside, feeling safe, fear of falling,
      and quality of life in community-living older persons: a randomized controlled
      trial.

PMID- 22587863
TI  - Falls in skilled nursing facilities associated with opioid use.

PMID- 22587864
TI  - Depressive symptoms, their management, and mortality in elderly people.

PMID- 22587865
TI  - Geriatric Depression Scale items and mortality in Italian elderly persons living
      at home.

PMID- 22587866
TI  - Natriuretic peptide concentrations in centenarians.

PMID- 22587867
TI  - Geriatric consultations offer help and maybe education.

PMID- 22587868
TI  - Five-year outcome of individuals with hip fracture admitted to a Singapore
      hospital: quality of life and survival rates after treatment.

PMID- 22587869
TI  - U.S. geriatricians and gastric cancer screening in elderly Korean-American men:
      differences from Korean geriatricians.

PMID- 22587870
TI  - Incidence and characteristics of metabolic disorders and vascular complications
      in individuals with Werner syndrome in Japan.

PMID- 22587871
TI  - Rehabilitation of elderly adults with severe cognitive impairment: it is time for
      evidence.

PMID- 22587873
TI  - Cyclooxygenase-2 ( COX -2) gene-765G/C polymorphism and advanced-stage
      endometriosis in Korean women.
AB  - PROBLEM: We investigated the association of COX -2 gene-765G/C polymorphism and
      risk of advanced-stage endometriosis in Korean women. METHOD OF STUDY: This study
      consisted of 268 women with advanced-stage endometriosis and 242 control women
      without endometriosis in Korea. Subjects were genotyped for the -765G/C
      polymorphism of the COX -2 gene by RFLP-PCR analysis. RESULTS: There were
      significant differences in the genotype distributions of the -765G/C polymorphism
      between patients with advanced-stage endometriosis and control subjects. The C
      allele for -765G/C was associated with significantly lower risk of advanced-stage
      endometriosis (OR, 0.14; 95% CI, 0.06-0.30). CONCLUSIONS: We have demonstrated a
      significant genetic association between the -765G/C polymorphism and advanced
      stage endometriosis in Korean women. The -765C allele may be protective against
      the development of the disease in Korean women.

PMID- 22587874
TI  - Molecular pathogenesis and targeted therapeutics in Ewing sarcoma/primitive
      neuroectodermal tumours.
AB  - BACKGROUND: Ewing sarcoma/PNET is managed with treatment paradigms involving
      combinations of chemotherapy, surgery, and sometimes radiation. Although the 5
      year survival rate of non-metastatic disease approaches 70%, those cases that are
      metastatic and those that recur have 5-year survival rates of less than 20%.
      Molecularly targeted treatments offer the potential to further improve treatment
      outcomes. METHODS: A PUBMED search was performed from 1997 to 2011. Published
      literature that included the topic of the Ewing sarcoma/PNET was also referenced.
      RESULTS: Insulin-like growth factor-1 receptor (IGF-1R) antagonists have
      demonstrated modest single agent efficacy in phase I/II clinical trials in Ewing
      sarcoma/PNET, but have a strong preclinical rationale. Based on in vitro and
      animal data, treatment using antisense RNA and cDNA oligonucleotides directed at
      silencing the EWS-FLI chimera that occurs in most Ewing sarcoma/PNET may have
      potential therapeutic importance. However drug delivery and degradation problems
      may limit this therapeutic approach. Protein-protein interactions can be targeted
      by inhibition of RNA helicase A, which binds to EWS/FLI as part of the
      transcriptional complex. Tumour necrosis factor related apoptosis inducing ligand
      induction using interferon has been used in preclinical models. Interferons may
      be incorporated into future chemotherapeutic treatment paradigms. Histone
      deacetylase inhibitors can restore TGF-beta receptor II allowing TFF-beta
      signalling, which appears to inhibit growth of Ewing sarcoma/PNET cell lines in
      vitro. Immunotherapy using allogeneic natural killer cells has activity in Ewing
      sarcoma/PNET cell lines and xenograft models. Finally, cyclin dependent kinase
      inhibitors such as flavopiridol may be clinically efficacious in relapsed Ewing
      sarcoma/PNET. CONCLUSION: Preclinical evidence exists that targeted therapeutics
      may be efficacious in the ESFT. IGF-1R antagonists have demonstrated efficacy in
      phase I/II clinical trials, although predicting responses remains a challenge.
      The future treatment of Ewing sarcoma/PNET is likely to be improved by these
      scientific advances.

PMID- 22587875
TI  - Auto-titrating versus fixed continuous positive airway pressure for the treatment
      of obstructive sleep apnea: a systematic review with meta-analyses.
AB  - BACKGROUND: Obstructive sleep apnea is a relatively common disorder that can lead
      to lost productivity and cardiovascular disease. The form of positive airway
      treatment that should be offered is unclear. METHODS: MEDLINE and the Cochrane
      Central Trials registry were searched for English language randomized controlled
      trials comparing auto-titrating positive airway pressure (APAP) with continuous
      positive airway pressure (CPAP) in adults with obstructive sleep apnea (inception
      through 9/2010). Six researchers extracted information on study design, potential
      bias, patient characteristics, interventions and outcomes. Data for each study
      were extracted by one reviewer and confirmed by another. Random effects model
      meta-analyses were performed for selected outcomes. RESULTS: Twenty-four
      randomized controlled trials met the inclusion criteria. In individual studies,
      APAP and fixed CPAP resulted in similar changes from baseline in the apnea
      hypopnea index, most other sleep study measures and quality of life. By meta
      analysis, APAP improved compliance by 11 minutes per night (95% CI, 3 to 19
      minutes) and reduced sleepiness as measured by the Epworth Sleepiness Scale by
      0.5 points (95% CI, 0.8 to 0.2 point reduction) compared with fixed CPAP. Fixed
      CPAP improved minimum oxygen saturation by 1.3% more than APAP (95% CI, 0.4 to
      2.2%). Studies had relatively short follow-up and generally excluded patients
      with significant comorbidities. No study reported on objective clinical outcomes.
      CONCLUSIONS: Statistically significant differences were found but clinical
      importance is unclear. Because the treatment effects are similar between APAP and
      CPAP, the therapy of choice may depend on other factors such as patient
      preference, specific reasons for non-compliance and cost.

PMID- 22587876
TI  - Where the bugs are: analyzing distributions of bacterial phyla by descriptor
      keyword search in the nucleotide database.
AB  - BACKGROUND: The associations between bacteria and environment underlie their
      preferential interactions with given physical or chemical conditions. Microbial
      ecology aims at extracting conserved patterns of occurrence of bacterial taxa in
      relation to defined habitats and contexts. RESULTS: In the present report the
      NCBI nucleotide sequence database is used as dataset to extract information
      relative to the distribution of each of the 24 phyla of the bacteria superkingdom
      and of the Archaea. Over two and a half million records are filtered in their
      cross-association with each of 48 sets of keywords, defined to cover natural or
      artificial habitats, interactions with plant, animal or human hosts, and physical
      chemical conditions. The results are processed showing: (a) how the different
      descriptors enrich or deplete the proportions at which the phyla occur in the
      total database; (b) in which order of abundance do the different keywords score
      for each phylum (preferred habitats or conditions), and to which extent are phyla
      clustered to few descriptors (specific) or spread across many (cosmopolitan); (c)
      which keywords individuate the communities ranking highest for diversity and
      evenness. CONCLUSIONS: A number of cues emerge from the results, contributing to
      sharpen the picture on the functional systematic diversity of prokaryotes.
      Suggestions are given for a future automated service dedicated to refining and
      updating such kind of analyses via public bioinformatic engines.

PMID- 22587877
TI  - A multivariate test of evolutionary constraints for thermal tolerance in
      Drosophila melanogaster.
AB  - Exposure to extreme temperatures is increasingly likely to impose strong
      selection on many organisms in their natural environments. The ability of
      organisms to adapt to such selective pressures will be determined by patterns of
      genetic variation and covariation. Despite increasing interest in thermal
      adaptation, few studies have examined the extent to which the genetic covariance
      between traits might constrain thermal responses. Furthermore, it remains unknown
      whether sex-specific genetic architectures will constrain responses to climatic
      selection. We used a paternal half-sibling breeding design to examine whether sex
      specific genetic architectures and genetic covariances between traits might
      constrain evolutionary responses to warming climates in a population of
      Drosophila melanogaster. Our results suggest that the sexes share a common
      genetic underpinning for heat tolerance as indicated by a strong positive inter
      sexual genetic correlation. Further, we found no evidence in either of the sexes
      that genetic trade-offs between heat tolerance and fitness will constrain
      responses to thermal selection. Our results suggest that neither trade-offs, nor
      sex-specific genetics, will significantly constrain an evolutionary response to
      climatic warming, at least in this population of D. melanogaster.

PMID- 22587878
TI  - Use of a geographic information system (GIS) in the medical response to the
      Fukushima nuclear disaster in Japan.
AB  - The Great East Japan Earthquake occurred on March 11, 2011. In the first 10 days
      after the event, information about radiation risks from the Fukushima Daiichi
      nuclear plant was unavailable, and the disaster response, including deployment of
      disaster teams, was delayed. Beginning on March 17, 2011, the Japan Medical
      Association used a geographic information system (GIS) to visualize the risk of
      radiation exposure in Fukushima. This information facilitated the decision to
      deploy disaster medical response teams on March 18, 2011.

PMID- 22587879
TI  - The clinical use of biomarkers as prognostic factors in Ewing sarcoma.
AB  - Ewing Sarcoma is the second most common primary bone sarcoma with 900 new
      diagnoses per year in Europe (EU27). It has a poor survival rate in the face of
      metastatic disease, with no more than 10% survival of the 35% who develop
      recurrence. Despite the remaining majority having localised disease,
      approximately 30% still relapse and die despite salvage therapies. Prognostic
      factors may identify patients at higher risk that might require differential
      therapeutic interventions. Aside from phenotypic features, quantitative
      biomarkers based on biological measurements may help identify tumours that are
      more aggressive. We audited the research which has been done to identify
      prognostic biomarkers for Ewing sarcoma in the past 15 years. We identified 86
      articles were identified using defined search criteria. A total of 11,625
      patients were reported, although this number reflects reanalysis of several
      cohorts. For phenotypic markers, independent reports suggest that tumour size > 8
      cm and the presence of metastasis appeared strong predictors of negative outcome.
      Good histological response (necrosis > 90%) after treatment appeared a
      significant predictor for a positive outcome. However, data proposing biological
      biomarkers for practical clinical use remain un-validated with only one secondary
      report published. Our recommendation is that we can stratify patients according
      to their stage and using the phenotypic features of metastases, tumour size and
      histological response. For biological biomarkers, we suggest a number of
      validating studies including markers for 9p21 locus, heat shock proteins,
      telomerase related markers, interleukins, tumour necrosis factors, VEGF pathway,
      lymphocyte count, and a number of other markers including Ki-67.

PMID- 22587880
TI  - ACTH-secreting pituitary microadenomas are associated with a higher prevalence of
      central hypothyroidism compared to other microadenoma types.
AB  - CONTEXT: Unlike pituitary macroadenomas, microadenomas (micros) are not commonly
      associated with hypopituitarism. In clinical practice, we have observed that
      patients with ACTH-secreting micros have a higher than expected prevalence of
      central hypothyroidism (HT), and we speculated that this effect might be because
      of glucocorticoid-induced suppression of the hypothalamic-pituitary-thyroid axis.
      OBJECTIVE: To determine whether there is a difference in the prevalence of
      central HT among ACTH micros compared to other types of microadenoma, and if so,
      to investigate whether this is directly related to the degree of
      hypercortisolism. DESIGN, SETTING AND PATIENTS: Retrospective study of 149 newly
      diagnosed patients with pituitary micros: 34 ACTH-secreting, 72 prolactin
      secreting (PRLomas) and 43 clinically nonfunctioning adenomas (NFAs). MAIN
      OUTCOMES MEASURES: Prevalence of central HT, correlation between normalized free
      T4 or TSH vs normalized urinary free cortisol (UFC) or salivary cortisol.
      RESULTS: The prevalence of central HT was significantly higher in the ACTH
      compared to the non-ACTH adenomas: 18% (ACTH), 1% (PRL) and 0% (NFAs). The mean
      normalized free T4 was lower in the ACTH micros compared to the non-ACTH micros
      (1.29 +/- 0.06 vs 1.50 +/- 0.23, P = 0.0001). There was no correlation between
      the degree of hypercortisolism, as reflected by 24-h urine free cortisol and
      salivary cortisol, and free T4 or TSH levels among the ACTH adenomas. Similarly,
      there were no differences in mean UFC or salivary cortisol between ACTH adenomas
      with and without central HT. Following transsphenoidal adenomectomy, central HT
      recovered in three of six patients with ACTH micros. CONCLUSIONS: These findings
      suggest that patients with ACTH-secreting microadenomas should always, at a
      minimum, undergo testing for central HT. However, given the potential for
      recovery of thyroid function following cure of Cushing disease, we recommend
      withholding thyroid hormone replacement until after pituitary surgery.

PMID- 22587881
TI  - Semiparametric maximum likelihood methods for analyzing genetic and environmental
      effects with case-control mother-child pair data.
AB  - Case-control mother-child pair design represents a unique advantage for
      dissecting genetic susceptibility of complex traits because it allows the
      assessment of both maternal and offspring genetic compositions. This design has
      been widely adopted in studies of obstetric complications and neonatal outcomes.
      In this work, we developed an efficient statistical method for evaluating joint
      genetic and environmental effects on a binary phenotype. Using a logistic
      regression model to describe the relationship between the phenotype and maternal
      and offspring genetic and environmental risk factors, we developed a
      semiparametric maximum likelihood method for the estimation of odds ratio
      association parameters. Our method is novel because it exploits two unique
      features of the study data for the parameter estimation. First, the correlation
      between maternal and offspring SNP genotypes can be specified under the
      assumptions of random mating, Hardy-Weinberg equilibrium, and Mendelian
      inheritance. Second, environmental exposures are often not affected by offspring
      genes conditional on maternal genes. Our method yields more efficient estimates
      compared with the standard prospective method for fitting logistic regression
      models to case-control data. We demonstrated the performance of our method
      through extensive simulation studies and the analysis of data from the Jerusalem
      Perinatal Study.

PMID- 22587882
TI  - Antenatal magnesium individual participant data international collaboration:
      assessing the benefits for babies using the best level of evidence (AMICABLE).
AB  - BACKGROUND: The primary aim of this study is to assess, using individual
      participant data (IPD) meta-analysis, the effects of administration of antenatal
      magnesium sulphate given to women at risk of preterm birth on important clinical
      outcomes for their child such as death and neurosensory disability. The secondary
      aim is to determine whether treatment effects differ depending on important pre
      specified participant and treatment characteristics, such as reasons at risk of
      preterm birth, gestational age, or type, dose and mode of administration of
      magnesium sulphate. METHODS:  DESIGN: The Antenatal Magnesium Individual
      Participant Data (IPD) International Collaboration: assessing the benefits for
      babies using the best level of evidence (AMICABLE) Group will perform an IPD meta
      analysis to answer these important clinical questions. SETTING/TIMELINE: The
      AMICABLE Group was formed in 2009 with data collection commencing late 2010.
      INCLUSION CRITERIA: Five trials involving a total 6,145 babies are eligible for
      inclusion in the IPD meta-analysis. PRIMARY STUDY OUTCOMES: For the
      infants/children: Death or cerebral palsy. For the women: Any severe maternal
      outcome potentially related to treatment (death, respiratory arrest or cardiac
      arrest). DISCUSSION: Results are expected to be publicly available in 2012.

PMID- 22587883
TI  - Transforming growth factor (TGF)-beta expression and activation mechanisms as
      potential targets for anti-tumor therapy and tumor imaging.
AB  - Cancer remains one of the leading causes of death in the developed countries and
      cancer mortality is expected to rise globally. Despite encouraging developments
      regarding targeted drugs, the most prevalent cancer mortality remains metastatic
      disease. Therefore, drugs that target cancer progression, invasion and metastasis
      are clearly needed. One of the most interesting targets in this setting is
      transforming growth factor beta (TGF-beta). TGF-beta can promote tumor growth,
      invasion and metastasis. However, TGF-beta also has a physiological, opposing
      role: maintaining tissue homeostasis and suppression of tumor progression. The
      window of effective TGF-beta targeting is therefore evidently small, which poses
      a clear challenge in selecting patients at the right time. Despite this
      complexity, several TGF-beta inhibitors are currently in clinical development,
      modulating TGF-beta production, activation or signaling. Still, specificity and
      long term toxicity remain unclear, emphasizing the importance of careful
      monitoring of clinical trials. Development and application of these drugs in the
      clinic require adequate insight and evaluation methods for the role of TGF-beta
      during tumor invasion and metastasis. In this review, presently available methods
      for clinical evaluation will be discussed, such as an ex vivo stimulation assay,
      TGF-beta response signature and molecular imaging techniques. Future clinical
      trials incorporating the validation of these evaluation methods will show which
      method will be most predictive and suitable for clinical application.

PMID- 22587884
TI  - Bacteraemia in Malawian neonates and young infants 2002-2007: a retrospective
      audit.
AB  - OBJECTIVES: To assess the causes of bacteraemia in young infants and
      susceptibility to first-line antibiotics (benzylpenicillin plus gentamicin) at
      the Queen Elizabeth Central Hospital (QECH), Malawi during 2002-2007. DESIGN:
      Retrospective analysis of demographic and microbiological data using laboratory
      records. SETTING: QECH is Malawi's largest hospital with 7000 neonates admitted
      annually, 9% for septicaemia. PATIENTS: All infants aged 60 days or less admitted
      to QECH that had a blood culture taken over the 6-year period. MAIN OUTCOME
      MEASURES: 6754 blood cultures were taken. 3323 organisms were isolated: one-third
      were pathogens, two-thirds contaminants. Gram-positive organisms (53%) were more
      common than gram-negatives (47%). Four organisms made up half of all pathogens:
      Staphylococcus aureus (15.3%), group B streptococci (13.5%), non-typhoidal
      salmonellae (12.6%) and Escherichia coli (10.5%). Apart from non-typhoidal
      salmonellae and Streptococcus pneumoniae, most organisms were more common in the
      first week of life than later. Overall, 28% of isolates during 2002-2007 were
      resistant to first-line antibiotic, higher than observed during 1996-2001 (22%).
      Penicillin susceptibility fluctuated while gram-negative resistance to gentamicin
      increased from 17% to 27% over the study period. CONCLUSIONS: In the QECH,
      pathogens causing young infant sepsis are an unusual mix of organisms seen in
      both developed and developing countries. Resistance to first-line antibiotics is
      higher than observed in most studies. Ongoing monitoring is needed and clinical
      outcome data would aid interpretation of findings. A high proportion of blood
      cultures were contaminated with skin flora-improved training and supervision of
      phlebotomists are needed to improve the utility of taking blood cultures.

PMID- 22587885
TI  - A cohort study of mortality predictors and characteristics of patients with
      combined pulmonary fibrosis and emphysema.
AB  - OBJECTIVES: Our purpose was to assess the clinical data, predictors of mortality
      and acute exacerbation (AE) in combined pulmonary fibrosis and emphysema (CPFE)
      patients. DESIGN: Single-centre retrospective cohort study. SETTING: Teaching
      hospital in Japan. PARTICIPANTS: We identified 93 CPFE patients with high
      resolution computed tomographic (HRCT) through multidisciplinary discussion.
      Patients who had connective tissue disease, drug-associated interstitial lung
      disease and occupationally related interstitial lung disease, such as asbestosis
      and silicosis, were excluded. INTERVENTIONS: There were no interventions.
      METHODS: Medical records and HRCT scans from January 2002 through December 2007
      were reviewed retrospectively at our hospital. Ninety-three patients had CPFE.
      RESULTS: The mean age of CPFE patients was 74 years. Idiopathic pulmonary
      fibrosis and non-specific interstitial pneumonia were observed as distinct HRCT
      patterns. Forty-two patients showed finger clubbing. Mean serum Krebs von den
      Lungen-6 (KL-6) and per cent predicted forced vital capacity (%FVC) were 1089
      IU/l, 63.86%, respectively. Twenty-two patients developed AE during observation
      period. Baseline KL-6 was a strong predictor of AE (OR=1.0016, p=0.009). Finger
      clubbing (HR=2.2620, p=0.015) and per cent predicted forced expiratory volume in
      one second/%FVC more than 1.2 (HR=1.9259, p=0.048) were independent predictors of
      mortality in CPFE. CONCLUSIONS: Baseline serum KL-6 was a useful predictor of AE
      (cut-off =1050, receiver operator characteristic curve: 0.7720), which occurred
      in 24% (22/93) of the CPFE patients. Finger clubbing and per cent predicted
      forced expiratory volume in one second/%FVC more than 1.2 were independent
      predictors of mortality.

PMID- 22587886
TI  - Neural activity and branching of embryonic retinal ganglion cell dendrites.
AB  - The shape of a neuron's dendritic arbor is critical for its function as it
      determines the number of inputs the neuron can receive and how those inputs are
      processed. During development, a neuron initiates primary dendrites that branch
      to form a simple arbor. Subsequently, growth occurs by a process that combines
      the extension and retraction of existing dendrites, and the addition of new
      branches. The loss and addition of the fine terminal branches of retinal ganglion
      cells (RGCs) is dependent on afferent inputs from its synaptic partners, the
      amacrine and bipolar cells. It is unknown, however, whether neural activity
      regulates the initiation of primary dendrites and their initial branching. To
      investigate this, Xenopus laevis RGCs developing in vivo were made to express
      either a delayed rectifier type voltage-gated potassium (KV) channel, Xenopus
      Kv1.1, or a human inward rectifying channel, Kir2.1, shown previously to modulate
      the electrical activity of Xenopus spinal cord neurons. Misexpression of either
      potassium channel increased the number of branch points and the total length of
      all the branches. As a result, the total dendritic arbor was bigger than for
      control green fluorescent protein-expressing RGCs and those ectopically
      expressing a highly related mutant non-functional Kv1.1 channel. Our data
      indicate that membrane excitability regulates the earliest differentiation of RGC
      dendritic arbors.

PMID- 22587887
TI  - Expression and cell distribution of metabotropic glutamate receptor 5 in the rat
      cortex following traumatic brain injury.
AB  - Traumatic brain injury (TBI)-released excessive glutamate resulted in the
      activation of glutamate receptors including the metabotropic glutamate receptor 5
      (mGluR5). To investigate the expression and cell distribution of mGluR5 in the
      rat cortex following TBI, western blot and quantitative real-time PCR were used
      to study the protein and mRNA level of mGluR5 respectively while
      immunohistochemistry analysis and double immunofluorescence with neural cell
      marker were used to define the cell distribution of mGluR5. Furthermore, we
      examined the effects of post-TBI administration of (R,S)-2-chloro-5
      hydroxyphenylglycine (CHPG), a selective mGluR5 agonist, on the neuronal
      degeneration in the cortex. In the present study, we found that the protein level
      of mGluR5 was up-regulated by traumatic brain injury, while TBI-induced mGluR5
      mRNA expression displayed biphasic changes with up-regulation in the early time
      and down-regulation in the late time after TBI. And neuron, astrocyte and
      microglia in the cortex after TBI all expressed mGluR5. Moreover, CHPG treatment
      significantly reduced the number of degenerating neurons detected by Fluoro-Jade
      C staining. These findings demonstrate that expression of mGluR5 differentially
      changes both spatially and temporally after TBI and may be related to the
      neuroprotection after TBI. Therefore, understanding the expression and cell
      distribution of mGluR5 after TBI may give insight into pathophysiology after TBI
      and provide a new target for the therapy of TBI.

PMID- 22587888
TI  - Perinatal exposure to low-dose methylmercury induces dysfunction of motor
      coordination with decreases in synaptophysin expression in the cerebellar granule
      cells of rats.
AB  - Methylmercury (MeHg) is an environmental pollutant that is toxic to the
      developing central nervous system (CNS) in children, even at low exposure levels.
      Perinatal exposure to MeHg is known to induce neurological symptoms with
      neuropathological changes in the CNS. However, the relationship between the
      neurological symptoms and neuropathological changes induced in offspring as a
      result of exposure to low-dose MeHg is not well defined. In the present study,
      neurobehavioral analyses revealed that exposure to a low level of MeHg (5 ppm in
      drinking water) during developmental caused a significant deficit in the motor
      coordination of rats in the rotating rod test. In contrast, general
      neuropathological findings, including neuronal cell death and the subsequent
      nerve inflammation, were not observed in the region of the cerebellum responsible
      for regulating motor coordination. Surprisingly, the expression of synaptophysin
      (SPP), a marker protein for synaptic formation, significantly decreased in
      cerebellar granule cells. These results showed that perinatal exposure to low
      dose MeHg causes neurobehavioral impairment without general neuropathological
      changes in rats. We demonstrated for the first time that exposure to low-dose
      MeHg during development induces the dysfunction of motor coordination due to
      changes of synaptic homeostasis in cerebellar granule cells.

PMID- 22587889
TI  - Fear memory for cue and context: opposite and time-dependent effects of a
      physiological dose of corticosterone in male BALB/c and C57BL/6J mice.
AB  - Highly emotional, stress reactive BALB/c mice secrete more corticosterone in
      response to fear conditioning than the low stress reactive C57BL/6J mice. Fear
      memory to cue and context differs between the strains. We injected corticosterone
      at physiological concentrations (250 MUg/kg i.p.) 30 min before fear
      conditioning. Fear memory was tested 48 and 72 h later. Although corticosterone
      had little effect on acquisition, it differentially affected fear memories in
      strain dependent manner: while BALB/c mice decreased freezing during cue and
      context episodes, C57BL/6J mice showed an overall increase in freezing. BALB/c
      mice showed extinction over days while no such extinction was seen in C57BL/6J
      mice. Evaluation of these data in the perspective of previous studies using the
      same fear conditioning paradigm with corticosterone injections 5 min before or
      immediately after acquisition, revealed the impact of corticosterone during
      conditioning on the strength of fear memories. In C57BL/6J mice the overall
      increase in fear memories was higher if corticosterone was injected 30 min pre
      acquisition than if injected 5 min pre. In contrast, BALB/c mice showed reduced
      fear memories when injected 30 min pre compared to that seen 5 min pre
      acquisition. Both strains showed decreased fear memories compared to vehicle if
      corticosterone was administered immediately after acquisition. We conclude that
      the timing of physiologically relevant, stress levels increase in corticosterone
      is essential for the processing of aversive events and the formation of fear
      memories. However, the quality of the effect depends on the genetic background.
      These findings contribute to the understanding of the etiology of stress-related
      disorders.

PMID- 22587891
TI  - Electrophysiological difference between mental state decoding and mental state
      reasoning.
AB  - Previous studies have explored the neural mechanism of Theory of Mind (ToM), but
      the neural correlates of its two components, mental state decoding and mental
      state reasoning, remain unclear. In the present study, participants were
      presented with various photographs, showing an actor looking at 1 of 2 objects,
      either with a happy or an unhappy expression. They were asked to either decode
      the emotion of the actor (mental state decoding task), predict which object would
      be chosen by the actor (mental state reasoning task), or judge at which object
      the actor was gazing (physical task), while scalp potentials were recorded.
      Results showed that (1) the reasoning task elicited an earlier N2 peak than the
      decoding task did over the prefrontal scalp sites; and (2) during the late
      positive component (240-440 ms), the reasoning task elicited a more positive
      deflection than the other two tasks did at the prefrontal scalp sites. In
      addition, neither the decoding task nor the reasoning task has no left/right
      hemisphere difference. These findings imply that mental state reasoning differs
      from mental state decoding early (210 ms) after stimulus onset, and that the
      prefrontal lobe is the neural basis of mental state reasoning.

PMID- 22587890
TI  - Evaluation of the effects of testosterone and luteinizing hormone on regulation
      of beta-amyloid in male 3xTg-AD mice.
AB  - During normal aging, men experience a significant decline in testosterone levels
      and a compensatory elevation in levels of gonadotropin luteinizing hormone (LH).
      Both low testosterone and elevated LH have been identified as significant risk
      factors for the development of Alzheimer's disease (AD) in men. It is unclear
      whether changes in testosterone or LH primarily underlie the relationship with
      AD, and therefore may be a more suitable therapeutic target. To examine this
      issue, we compared levels of beta-amyloid (Abeta) immunoreactivity in male 3xTg
      AD mice under varying experimental conditions associated with relatively low or
      high levels of testosterone and/or LH. In gonadally intact mice, Abeta
      accumulation increased after treatment with the gonadotropin-releasing hormone
      agonist leuprolide, which inhibits the hypothalamic-pituitary-gonadal (HPG) axis
      and reduces both testosterone and LH levels. In gonadectomized (GDX) mice with
      low testosterone and high LH, we also observed increased Abeta levels. Treatment
      of GDX mice with testosterone significantly reduced Abeta levels. In contrast,
      leuprolide did not significantly decrease Abeta levels and moreover, inhibited
      the Abeta-lowering effect of testosterone. Evaluation of hippocampal-dependent
      behavior revealed parallel findings, with performance in GDX mice improved by
      testosterone but not leuprolide. These data suggest that Abeta-lowering actions
      of testosterone are mediated directly by androgen pathways rather than indirectly
      via regulation of LH and the HPG axis. These findings support the clinical
      evaluation of androgen therapy in the prevention and perhaps treatment of AD in
      hypogonadal men.

PMID- 22587892
TI  - Histone deacetylase inhibitors enhance expression of NKG2D ligands in Ewing
      sarcoma and sensitize for natural killer cell-mediated cytolysis.
AB  - BACKGROUND: Ewing sarcoma patients have a poor prognosis despite multimodal
      therapy. Integration of combination immunotherapeutic strategies into first
      /second-line regimens represents promising treatment options, particularly for
      patients with intrinsic or acquired resistance to conventional therapies. We
      evaluated the susceptibility of Ewing sarcoma to natural killer cell-based
      combination immunotherapy, by assessing the capacity of histone deacetylase
      inhibitors to improve immune recognition and sensitize for natural killer cell
      cytotoxicity. METHODS: Using flow cytometry, ELISA and immunohistochemistry,
      expression of natural killer cell receptor ligands was assessed in chemotherapy
      sensitive/-resistant Ewing sarcoma cell lines, plasma and tumours. Natural killer
      cell cytotoxicity was evaluated in Chromium release assays. Using ATM/ATR
      inhibitor caffeine, the contribution of the DNA damage response pathway to
      histone deacetylase inhibitor-induced ligand expression was assessed. RESULTS:
      Despite comparable expression of natural killer cell receptor ligands,
      chemotherapy-resistant Ewing sarcoma exhibited reduced susceptibility to resting
      natural killer cells. Interleukin-15-activation of natural killer cells overcame
      this reduced sensitivity. Histone deacetylase inhibitor-pretreatment induced
      NKG2D-ligand expression in an ATM/ATR-dependent manner and sensitized for NKG2D
      dependent cytotoxicity (2/4 cell lines). NKG2D-ligands were expressed in vivo,
      regardless of chemotherapy-response and disease stage. Soluble NKG2D-ligand
      plasma concentrations did not differ between patients and controls. CONCLUSION:
      Our data provide a rationale for combination immunotherapy involving immune
      effector and target cell manipulation in first-/second-line treatment regimens
      for Ewing sarcoma.

PMID- 22587893
TI  - The kinomes of apicomplexan parasites.
AB  - Protein phosphorylation plays a fundamental role in the biology of apicomplexan
      parasites. Many apicomplexan protein kinases are substantially different from
      their mammalian orthologues, and thus constitute a landscape of potential drug
      targets. Here, we integrate genomic, biochemical, genetic and evolutionary
      information to provide an integrated and up-to-date analysis of twelve
      apicomplexan kinomes. All kinome sequences are available through the Kinomer
      database.

PMID- 22587894
TI  - Effectiveness of brief interventions as part of the screening, brief intervention
      and referral to treatment (SBIRT) model for reducing the non-medical use of
      psychoactive substances: a systematic review protocol.
AB  - BACKGROUND: There is a significant public health burden associated with substance
      use in Canada. The early detection and/or treatment of risky substance use has
      the potential to dramatically improve outcomes for those who experience harms
      from the non-medical use of psychoactive substances, particularly adolescents
      whose brains are still undergoing development. The Screening, Brief Intervention,
      and Referral to Treatment model is a comprehensive, integrated approach for the
      delivery of early intervention and treatment services for individuals
      experiencing substance use-related harms, as well as those who are at risk of
      experiencing such harm. METHODS: This article describes the protocol for a
      systematic review of the effectiveness of brief interventions as part of the
      Screening, Brief Intervention, and Referral to Treatment model for reducing the
      non-medical use of psychoactive substances. Studies will be selected in which
      brief interventions target non-medical psychoactive substance use (excluding
      alcohol, nicotine, or caffeine) among those 12 years and older who are
      opportunistically screened and deemed at risk of harms related to psychoactive
      substance use. We will include one-on-one verbal interventions and exclude non
      verbal brief interventions (for example, the provision of information such as a
      pamphlet or online interventions) and group interventions. Primary, secondary and
      adverse outcomes of interest are prespecified. Randomized controlled trials will
      be included; non-randomized controlled trials, controlled before-after studies
      and interrupted time series designs will be considered in the absence of
      randomized controlled trials. We will search several bibliographic databases (for
      example, MEDLINE, EMBASE, CINAHL, PsycINFO, CORK) and search sources for grey
      literature. We will meta-analyze studies where possible. We will conduct subgroup
      analyses, if possible, according to drug class and intervention setting.
      DISCUSSION: This review will provide evidence on the effectiveness of brief
      interventions as part of the Screening, Brief Intervention, and Referral to
      Treatment protocol aimed at the non-medical use of psychoactive substances and
      may provide guidance as to where future research might be most beneficial.

PMID- 22587895
TI  - Principles of Emergency Department facility design for optimal management of mass
      casualty incidents.
AB  - INTRODUCTION: The Emergency Department (ED) is the triage, stabilization and
      disposition unit of the hospital during a mass-casualty incident (MCI). With most
      EDs already functioning at or over capacity, efficient management of an MCI
      requires optimization of all ED components. While the operational aspects of MCI
      management have been well described, the architectural/structural principles have
      not. Further, there are limited reports of the testing of ED design components in
      actual MCI events. The objective of this study is to outline the important
      infrastructural design components for optimization of ED response to an MCI, as
      developed, implemented, and repeatedly tested in one urban medical center.
      REPORT: In the authors' experience, the most important aspects of ED design for
      MCI have included external infrastructure and promoting rapid lockdown of the
      facility for security purposes; an ambulance bay permitting efficient vehicle
      flow and casualty discharge; strategic placement of the triage location; patient
      tracking techniques; planning adequate surge capacity for both patients and
      staff; sufficient command, control, communications, computers, and information;
      well-positioned and functional decontamination facilities; adequate, well-located
      and easily distributed medical supplies; and appropriately built and functioning
      essential services. DISCUSSION: Designing the ED to cope well with a large
      casualty surge during a disaster is not easy, and it may not be feasible for all
      EDs to implement all the necessary components. However, many of the components of
      an appropriate infrastructural design add minimal cost to the normal expenditures
      of building an ED. CONCLUSION: This study highlights the role of design and
      infrastructure in MCI preparedness in order to assist planners in improving their
      ED capabilities. Structural optimization calls for a paradigm shift in the
      concept of structural and operational ED design, but may be necessary in order to
      maximize surge capacity, department resilience, and patient and staff safety.

PMID- 22587896
TI  - Temperature-tolerant COLD-PCR reduces temperature stringency and enables robust
      mutation enrichment.
AB  - BACKGROUND: Low-level mutations in clinical tumor samples often reside below
      mutation detection limits, thus leading to false negatives that may impact
      clinical diagnosis and patient management. COLD-PCR (coamplification at lower
      denaturation temperature PCR) is a technology that magnifies unknown mutations
      during PCR, thus enabling downstream mutation detection. However, a practical
      difficulty in applying COLD-PCR has been the requirement for strict control of
      the denaturation temperature for a given sequence, to within +/-0.3  degrees C.
      This requirement precludes simultaneous mutation enrichment in sequences of
      substantially different melting temperature (T(m)) and limits the technique to a
      single sequence at a time. We present a temperature-tolerant (TT) approach (TT
      COLD-PCR) that reduces this obstacle. METHODS: We describe thermocycling programs
      featuring a gradual increase of the denaturation temperature during COLD-PCR.
      This approach enabled enrichment of mutations when the cycling achieves the
      appropriate critical denaturation temperature of each DNA amplicon that is being
      amplified. Validation was provided for KRAS (v-Ki-ras2 Kirsten rat sarcoma viral
      oncogene homolog) and TP53 (tumor protein p53) exons 6-9 by use of dilutions of
      mutated DNA, clinical cancer samples, and plasma-circulating DNA. RESULTS: A
      single thermocycling program with a denaturation-temperature window of 2.5-3.0 
      degrees C enriches mutations in all DNA amplicons simultaneously, despite their
      different T(m)s. Mutation enrichments of 6-9-fold were obtained with TT-full-COLD
      PCR. Higher mutation enrichments were obtained for the other 2 forms of COLD-PCR,
      fast-COLD-PCR, and ice-COLD-PCR. CONCLUSIONS: Low-level mutations in diverse
      amplicons with different T(m)s can be mutation enriched via TT-COLD-PCR provided
      that their T(m)s fall within the denaturation-temperature window applied during
      amplification. This approach enables simultaneous enrichment of mutations in
      several amplicons and increases significantly the versatility of COLD-PCR.

PMID- 22587897
TI  - Molecular evolution of vertebrate Toll-like receptors: evolutionary rate
      difference between their leucine-rich repeats and their TIR domains.
AB  - Toll-like receptors (TLRs) that initiate an innate immune response contain an
      extracellular leucine rich repeat (LRR) domain and an intracellular Toll IL
      receptor (TIR) domain. There are fifteen different TLRs in vertebrates. The LRR
      domains, which adopt a solenoid structure, usually have higher rates of evolution
      than do the TIR globular domains. It is important to understand the molecular
      evolution and functional roles of TLRs from this standpoint. Both pairwise
      genetic distances and Ka/Ks's (the ratios between non synonymous and synonymous
      substitution rates) were compared between the LRR domain and the TIR domain of
      366 vertebrate TLRs from 96 species (from fish to primates). In fourteen members
      (TLRs 1, 2, 3, 4, 5, 6, 7, 8, 9, 11/12, 13, 14, 21, and 22/23) the LRR domains
      evolved significantly more rapidly than did the corresponding TIR domains. The
      evolutionary rates of the LRR domains are significantly different among these
      members; LRR domains from TLR3 and TLR7 from primates to fishes have the lowest
      rate of evolution. In contrast, the fifteenth member, TLR10, shows no significant
      differences; its TIR domain is not highly conserved. The present results suggest
      that TLR10 may have a different function in signaling from those other members
      and that a higher conservation of TLR3 and TLR7 may reflect a more ancient
      mechanism and/or structure in the innate immune response system. Gene conversions
      are suggested to have occurred in platypus TLR6 and TLR10. This study provides
      new insight about structural and functional diversification of vertebrate TLRs.

PMID- 22587899
TI  - Arteries dominate volume changes during brief functional hyperemia: evidence from
      mathematical modelling.
AB  - Variations in local neural activity are accompanied by rapid, focal changes in
      cerebral blood flow and volume. While a range of observations have shown that
      dilation occurs in cerebral arteries, there is conflicting evidence about the
      significance of volume changes in post-arteriole vessels. Here, we reconcile the
      competing observations using a new mathematical model of the hemodynamic
      response. First, we followed a 'top down' approach, without constraining the
      model, but using experimental observations at progressively more detailed scales
      to ensure physiological behaviour. Then, we blocked dilation of post-arteriole
      vessels, and predicted observations at progressively more aggregated scales (a
      'bottom up' approach). Predictions of blood flow, volume, velocity, and vessel
      diameter changes were consistent with experimental observations. Interestingly,
      the model predicted small, slow increases in capillary and venous diameter in
      agreement with recent in vivo data. Blocking dilation in these vessels led to
      erroneous volume predictions. The results are further evidence that arteries make
      up the majority of blood volume increases during brief functional activation.
      However, dilation of capillaries and veins appears to be increasingly significant
      during extended stimulation. These are important considerations when interpreting
      results from different neurovascular imaging modalities.

PMID- 22587900
TI  - Overlapping activity in anterior insula during interoception and emotional
      experience.
AB  - Classic theories of emotion posit that awareness of one's internal bodily states
      (interoception) is a key component of emotional experience. This view has been
      indirectly supported by data demonstrating similar patterns of brain activity -
      most importantly, in the anterior insula - during both interoception and emotion
      elicitation. However, no study has directly compared these two phenomena within
      participants, leaving it unclear whether interoception and emotional experience
      truly share the same functional neural architecture. The current study addressed
      this gap in knowledge by examining the neural convergence of these two phenomena
      within the same population. In one task, participants monitored their own
      heartbeat; in another task they watched emotional video clips and rated their own
      emotional responses to the videos. Consistent with prior research, heartbeat
      monitoring engaged a circumscribed area spanning insular cortex and adjacent
      inferior frontal operculum. Critically, this interoception-related cluster also
      was engaged when participants rated their own emotion, and activity here
      correlated with the trial-by-trial intensity of participants' emotional
      experience. These findings held across both group-level and individual
      participant-level approaches to localizing interoceptive cortex. Together, these
      data further clarify the functional role of the anterior insula and provide novel
      insights about the connection between bodily awareness and emotion.

PMID- 22587898
TI  - Neuroanatomical correlates of visual car expertise.
AB  - Expertise in non-visual domains such as musical performance is associated with
      differences in gray matter volume of particular regions of the human brain.
      Whether this is also the case for expertise in visual object recognition is
      unknown. Here we tested whether individual variability in the ability to
      recognize car models, from novice performance to high level of expertise, is
      associated with specific structural changes in gray matter volume. We found that
      inter-individual variability in expertise with cars was significantly and
      selectively correlated with gray matter volume in prefrontal cortex. Inter
      individual differences in the recognition of airplanes, that none of the
      participants had expertise with, were correlated with structural variability of
      regions bordering the visual cortex. These results highlight the role of
      prefrontal regions outside the visual cortex in accessing and processing visual
      knowledge about objects from the domain of expertise and suggest that expertise
      in visual object recognition may entail structural changes in regions associated
      with semantic knowledge.

PMID- 22587901
TI  - Significant enhancement in the thermoelectric performance of a bismuth telluride
      nanocompound through brief fabrication procedures.
AB  - A binary BiTe nanocompound for thermoelectric applications was prepared via a
      water-based chemical reaction under atmospheric conditions. We attempted to
      increase the carrier mobility of the nanocompound by adopting a post-thermal
      treatment consisting of calcination and reduction at different temperatures. We
      also tried to control the carrier density of the compound by adjusting the
      stoichiometry of the atomic constituents. We measured other transport properties
      (i.e., electrical resistivity, Seebeck coefficient, and thermal conductivity) and
      observed how these properties were affected by both the carrier mobility and the
      carrier density. We derived the thermoelectric performance, as captured by the
      figure of merit (ZT), from the transport properties and discussed the effect of
      such properties on the ZT value. The nanocompound exhibited a very competent ZT
      value (0.91 at 100  degrees C), which is one of the best thermoelectric
      performances of chemically synthesized BiTe materials. 

PMID- 22587902
TI  - Serum tumor markers in pediatric osteosarcoma: a summary review.
AB  - Osteosarcoma is the most common primary high-grade bone tumor in both
      adolescents and children. Early tumor detection is key to ensuring effective
      treatment. Serum marker discovery and validation for pediatric osteosarcoma has
      accelerated in recent years, coincident with an evolving understanding of
      molecules and their complex interactions, and the compelling need for improved
      pediatric osteosarcoma outcome measures in clinical trials. This review gives a
      short overview of serological markers for pediatric osteosarcoma, and highlights
      advances in pediatric osteosarcoma-related marker research within the past year.
      Studies in the past year involving serum markers in patients with pediatric
      osteosarcoma can be assigned to one of four categories, i.e., new approaches and
      new markers, exploratory studies in specialized disease subsets, large cross
      sectional validation studies, and longitudinal studies, with and without an
      intervention.Most of the studies have examined the association of a serum marker
      with some aspect of the natural history of pediatric osteosarcoma. As illustrated
      by the many studies reviewed, several serum markers are emerging that show a
      credible association with disease modification. The expanding pool of informative
      osteosarcoma-related markers is expected to impact development of therapeutics
      for pediatric osteosarcoma positively and, it is hoped, ultimately clinical care.
      Combinations of serum markers of natural immunity, thyroid hormone homeostasis,
      and bone tumorigenesis may be undertaken together in patients with pediatric
      osteosarcoma. These serum markers in combination may do better. The potential
      effect of an intrinsic dynamic balance of tumor angiogenesis residing within a
      single hormone (tri-iodothyronine) is an attractive concept for regulation of
      vascularization in pediatric osteosarcoma.

PMID- 22587904
TI  - Rejected.

PMID- 22587903
TI  - Quantifying the effect of environment stability on the transcription factor
      repertoire of marine microbes.
AB  - BACKGROUND: DNA-binding transcription factors (TFs) regulate cellular functions
      in prokaryotes, often in response to environmental stimuli. Thus, the environment
      exerts constant selective pressure on the TF gene content of microbial
      communities. Recently a study on marine Synechococcus strains detected
      differences in their genomic TF content related to environmental adaptation, but
      so far the effect of environmental parameters on the content of TFs in bacterial
      communities has not been systematically investigated. RESULTS: We quantified the
      effect of environment stability on the transcription factor repertoire of marine
      pelagic microbes from the Global Ocean Sampling (GOS) metagenome using
      interpolated physico-chemical parameters and multivariate statistics. Thirty-five
      percent of the difference in relative TF abundances between samples could be
      explained by environment stability. Six percent was attributable to spatial
      distance but none to a combination of both spatial distance and stability. Some
      individual TFs showed a stronger relationship to environment stability and space
      than the total TF pool. CONCLUSIONS: Environmental stability appears to have a
      clearly detectable effect on TF gene content in bacterioplanktonic communities
      described by the GOS metagenome. Interpolated environmental parameters were shown
      to compare well to in situ measurements and were essential for quantifying the
      effect of the environment on the TF content. It is demonstrated that
      comprehensive and well-structured contextual data will strongly enhance our
      ability to interpret the functional potential of microbes from metagenomic data.

PMID- 22587905
TI  - Hydrothermal synthesis and humidity sensing property of ZnO nanostructures and
      ZnO-In(OH)3 nanocomposites.
AB  - Prism- and raspberry-like ZnO nanoparticles and ZnO-In(OH)(3) nanocomposites were
      prepared by template free hydrothermal method. XRD investigations and microscopic
      studies showed that pill-like In(OH)(3) particles with body-centered cubic
      crystal structure formed on the surface of ZnO nanoparticles resulting in
      increased specific surface area. TEM-EDX mapping images demonstrated that not
      only nanocomposite formation took place in the course of the synthesis, but zinc
      ions were also built into the crystal lattice of the In(OH)(3). However, only
      undoped In(OH)(3) was found on the surface of the pill-like particle aggregates
      by XPS analyses. The raspberry- and prism-like ZnO particles exhibit strong
      visible emission with a maximum at 585 and 595 nm, respectively, whose intensity
      significantly increase due to nanocomposite formation. Photoelectric
      investigations revealed that photocurrent intensity decreased with increasing
      indium ion concentration during UV light excitation, which was explained by
      increase in visible fluorescence emission. QCM measurements showed that
      morphology of ZnO and concentration of In(OH)(3) had an influence on the water
      vapor sensing properties.

PMID- 22587906
TI  - Effect of systemic kynurenine on cortical spreading depression and its modulation
      by sex hormones in rat.
AB  - BACKGROUND: The aura symptoms in migraine are most likely due to cortical
      spreading depression (CSD). CSD is favored by NMDA receptor activation and
      increased cortical excitability. The latter probably explains why migraine with
      aura may appear when estrogen levels are high, like during pregnancy. Kynurenic
      acid, a derivative of tryptophan metabolism, is an endogenous NMDA receptor
      antagonist whose cerebral concentrations can be augmented by systemic
      administration of its precursor L-kynurenine. OBJECTIVE: To determine if
      exogenous administration of L-kynurenine is able to influence KCl-induced CSD in
      rat, if the effect is sex-dependent and if it differs in females between the
      phases of the estrous cycle. METHODS: Adult Sprague-Dawley rats (n=8/group)
      received intraperitoneal (i.p.) injections of L-kynurenine (L-KYN, 300 mg/kg), L
      KYN combined with probenecid (L-KYN+PROB) that increases cortical concentration
      of KYNA by blocking its excretion from the central nervous system, probenecid
      alone (PROB, 200 mg/kg) or NaCl. Cortical kynurenic acid concentrations were
      determined by HPLC (n=7). Thirty minutes after the injections, CSDs were elicited
      by application of 1M KCl over the occipital cortex and recorded by DC
      electrocorticogram. In NaCl and L-KYN groups, supplementary females were added
      and CSD frequency was analyzed respective to the phases of the estrous cycle
      determined by vaginal smears. RESULTS: In both sexes, PROB, L-KYN and L-KYN+PROB
      increased cortical kynurenic acid level. PROB, L-KYN and L-KYN+PROB with
      increasing potency decreased CSD frequency in female rats, while in males such an
      effect was significant only for L-KYN+PROB. The inhibitory effect of L-KYN on CSD
      frequency in females was most potent in diestrus. CONCLUSION: L-Kynurenine
      administration suppresses CSD, most likely by increasing kynurenic acid levels in
      the cortex. Females are more sensitive to this suppressive effect of L-kynurenine
      than males. These results emphasize the role of sex hormones in migraine and open
      interesting novel perspectives for its preventive treatment.

PMID- 22587907
TI  - Pioglitazone attenuates the detrimental effects of advanced glycation end
      products in the pancreatic beta cell line HIT-T15.
AB  - Pioglitazone is an anti-diabetic agent that preserves pancreatic beta cell mass
      and improves their function. Advanced Glycation End-Products (AGEs) are
      implicated in diabetic complications. We previously demonstrated that exposure of
      the pancreatic islet cell line HIT-T15 to high concentrations of AGEs
      significantly decreases cell proliferation and insulin secretion, and affects
      transcription factors regulating insulin gene transcription. The aim of this work
      was to investigate the effects of Pioglitazone on the function and viability of
      HIT-T15 cells cultured with AGEs. HIT-T15 cells were cultured for 5 days in the
      presence of AGEs alone, or supplemented with 1 MUmol/l Pioglitazone. Cell
      viability, insulin secretion and insulin content, redox balance, expression of
      the AGE receptor (RAGE), and NF-kB activation were then determined. The results
      showed that Pioglitazone protected beta cells against AGEs-induced apoptosis and
      necrosis. Moreover, Pioglitazone restored the redox balance and improved the
      responsiveness to low glucose concentration. Adding Pioglitazone to the AGEs
      culture attenuated NF-kB phosphorylation, and prevented AGEs to down-regulate
      IkBalpha expression. These findings suggest that Pioglitazone protects beta cells
      from the dangerous effects of AGEs.

PMID- 22587908
TI  - Salt-induced downregulation of renal aquaporins is prevented by losartan.
AB  - AIMS: The purpose of this study was to investigate the expression of aquaporin-1
      (AQP-1) and aquaporin-2 (AQP-2) in the renal tubule of rats fed with a high-salt
      diet and its modulation by the AT1 receptor blocker losartan. MAIN METHODS: The
      experiments were performed in four groups of rats fed for 3 weeks with the
      following diets: regular rat chow (NS); high-salt (8% NaCl) chow (HS), NS plus
      losartan (NS-L) and HS plus losartan (HS-L). Losartan (40 mg x kg(-1)) was
      administered in the drinking water. Systolic blood pressure (SBP) and renal
      function were evaluated. The intrarenal levels of angiotensin II (Ang II), TGF
      beta(1), alpha-smooth muscle actin (alpha-SMA), endothelial nitric oxide synthase
      (eNOS), AQP-1 and AQP-2 were determined by immunohistochemistry. AQP-1 and AQP-2
      protein levels were measured by western blot analysis. KEY FINDINGS: A high
      sodium diet downregulated AQP-1 and AQP-2 expression levels in the proximal
      tubule and collecting duct, respectively. The high-sodium diet also induced Ang
      II, TGF-beta(1) and alpha-SMA overexpression and decreased eNOS expression in the
      renal cortex and medulla. Losartan increased the diuresis and natriuresis,
      favoring urinary sodium concentration. Additionally, losartan prevented the
      profibrogenic response, decreasing Ang II, TGF-beta(1) and alpha-SMA levels and
      normalizing AQP-2 expression in the HS-L group. AQP-1 expression was upregulated
      by losartan in both the NS-L and HS-L groups. SIGNIFICANCE: These results show
      that increased intrarenal Ang II in rats fed with a high-salt diet downregulates
      renal AQP-1 and AQP-2 expressions. In addition, although losartan increased
      diuresis and natriuresis, it prevented the downregulation of aquaporins, favoring
      urinary sodium concentration.

PMID- 22587909
TI  - Early intervention with liraglutide improves glucose tolerance without affecting
      islet microcirculation in young Goto-Kakizaki rats.
AB  - Liraglutide, an analog of glucagon-like peptide-1 (GLP-1), is an effective anti
      diabetic agent with few side effects. Since native GLP-1 exerts vascular effects,
      we investigated changes in pancreatic islet blood flow using a non-radioactive
      microsphere technique, as well as insulin concentration and glucose tolerance
      after 17 day treatment with liraglutide in 6-week-old Goto-Kakizaki (GK) rats.
      Compared to saline-treated control GK rats, liraglutide limited body weight gain,
      decreased glycemia, improved glucose tolerance and lowered serum insulin
      concentration. Neither pancreatic or islet blood flow, nor pancreatic insulin
      content, was affected by liraglutide treatment. We conclude that early
      intervention with liraglutide decreases glycemia and improves glucose tolerance,
      thus halting the natural progression towards diabetes, without affecting islet
      microcirculation or pancreatic insulin content in young female GK rats.

PMID- 22587910
TI  - Effects of maternal captopril treatment during late pregnancy on neonatal lung
      development in rats.
AB  - The renin-angiotensin system (RAS) has been implicated in pulmonary hypertension
      and pulmonary fibrosis. In the present study, we examined the effects of maternal
      exposure to captopril (2.85 mg/kg/day) during late pregnancy (G13-G21) on
      postnatal rat lung development. Treatment with captopril during late pregnancy
      caused a significant decrease in ACE activity in P0 rats. Body weight decreased
      at P0 (p<0.001), P8 and P15 (p<0.01) in captopril-treated rats. Lung weight of P0
      and P8 pups was lower in treated-animals (p<0.05). Lungs from captopril-treated
      animals showed impaired alveolar formation, with enlarged distal airway spaces at
      P8, P15 and P30. Interalveolar wall distance measured by mean linear intercept
      increased in treated vs. age-matched animals at P8, P15 (p<0.001) and P30
      (p<0.05) resembling new bronchopulmonary dysplasia. In control animals, the
      proliferating cell nuclear antigen (PCNA) marker was higher at P0 and then drops
      gradually, while in captopril-treated animals PCNA marker remains higher at all
      stages studied. alpha-Smooth muscle actin (alpha-SMA), a marker of fibroblast
      differentiation into myofibroblasts, was higher at the tips of developing
      secondary septa in captopril-treated lungs at P8 and P15. The increased
      expression of PCNA and alpha-SMA in treated pups suggest that beyond the effect
      caused by captopril, the developing lungs have the capacity to recover once the
      treatment was stopped. Taking together the low weight, histomorphological changes
      and increased expression of cellular markers caused by ACE inhibition during late
      pregnancy, it appears that the RAS could be an intrinsic factor involved in
      secondary septa formation during lung development.

PMID- 22587911
TI  - Evidence for the persistence of the land planarian species Microplana terrestris
      (Muller, 1774) (Platyhelminthes, Tricladida) in microrefugia during the Last
      Glacial Maximum in the northern section of the Iberian Peninsula.
AB  - The land planarian species Microplana terrestris (Muller, 1774), shows a wide
      distribution in the north of the Iberian Peninsula, where mature humid forests
      can be found. Since most terrestrial planarians require the presence and good
      condition of wet forests to survive, a parallel evolution of the taxon and its
      habitat might be expected. Performing molecular analyses (mitochondrial
      cytochrome oxidase I and nuclear ITS-1 genes) we estimated the demography and
      biogeographic history of the species in that region. Our results show the species
      to present levels of genetic diversity likely originating before the Pleistocene.
      However, it presents a genetic structure that presumably resulted from its
      survival in various refugees during the Pleistocene glacial cycles. The two main
      genetic groups, present on the Iberian Peninsula, seem to have different origins:
      the western one being of Iberian origin, while the eastern group may have been
      the result of a re-colonization from the north. In both cases, their
      biogeographical history mirrors their habitat range movements, reinforcing the
      phylogeographical hypothesis put forward for its preferred habitat, i.e. humid
      forests.

PMID- 22587912
TI  - Evaluation of patient involvement in a systematic review and meta-analysis of
      individual patient data in cervical cancer treatment.
AB  - BACKGROUND: In April 2005, researchers based at the Medical Research Council
      Clinical Trials Unit, set out to involve women affected by cervical cancer in a
      systematic review and meta-analysis of individual patient data to evaluate
      treatments for this disease. Each of the women had previously been treated for
      cervical cancer. Following completion of the meta-analysis, we aimed to evaluate
      the process of involvement from the researcher and research partner perspective.
      METHODS: An advisory group was first established to give advice on recruiting,
      supporting and involving women and led to efforts to recruit women to take part
      in the systematic review using different approaches. Evaluation of the process
      and outcomes of the partnership between the systematic reviewers and the
      patients, in respect to what the partnership achieved; what worked well and what
      were the difficulties; what was learned and the resource requirements, took place
      during the conduct of the meta-analysis and again after completion of the
      project. RESULTS: Six women, each of whom had received treatments for cervical
      cancer, were recruited as Patient Research Partners and five of these women
      subsequently took part in a variety of activities around the systematic review.
      They attended progress meetings and all but one attended a meeting at which the
      first results of the review were presented to all collaborators and gave
      feedback. Three of the women also became involved in a further related research
      project which led to an editorial publication from the patient perspective and
      also participated, along with two lead researchers, in the evaluation of the
      process and outcomes. While they were generally positive about the experience,
      one Patient Research Partner questioned the extent of the impact patients could
      make to the systematic review process. CONCLUSIONS: In general, researchers and
      patient research partners felt that they had learned a lot from the process and
      considered it to have been a positive experience. The researchers felt that
      because of resource implications, patient involvement in future systematic
      reviews would probably have to be prioritized to those in which the greatest
      impacts could be achieved.

PMID- 22587913
TI  - Plastic-syringe induced silicone contamination in organic photovoltaic
      fabrication: implications for small-volume additives.
AB  - Herein, the implications of silicone contamination found in solution-processed
      conjugated polymer solar cells are explored. Similar to a previous work based on
      molecular cells, we find this contamination as a result of the use of plastic
      syringes during fabrication. However, in contrast to the molecular case, we find
      that glass-syringe fabricated devices give superior performance than plastic
      syringe fabricated devices in poly(3-hexylthiophene)-based cells. We find that
      the unintentional silicone addition alters the solution's wettability, which
      translates to a thinner, less absorbent film on spinning. With many groups
      studying the effects of small-volume additives, this work should be closely
      considered as many of these additives may also directly alter the solutions'
      wettability, or the amount of silicone dissolved off the plastic syringes, or
      both. Thereby, film thickness, which generally is not reported in detail, can
      vary significantly from device to device. 

PMID- 22587914
TI  - The angiogenic response is dependent on ultrasound contrast agent concentration.
AB  - OBJECTIVE: Ultrasound (US) and ultrasound contrast agents (UCAs) provide a way to
      noninvasively induce targeted angiogenesis. However, there exists a lack of
      understanding regarding the mechanisms of this process that has impeded progress.
      This study sought to characterize the angiogenic response, by both exploring the
      role of UCA concentration ([UCA]) in bioeffect induction at 0 days post exposure
      (DPE) and assessing the bioeffect as a possible potentiator of angiogenesis at 5
      DPE. METHODS: A 1-MHz ultrasonic transducer was used to expose the gracilis
      muscles of Sprague Dawley rats for 5 min with a 10-MUs pulse duration, 10-Hz
      pulse repetition frequency, and 0.7-MPa peak rarefactional acoustic pressure
      (pr). Four [UCA]s were tested: 0x (saline), 1*, 5*, and 10*, where 1* is 5%
      Definity by volume of solution. Evans blue dye (EBD) was used to quantify changes
      in acute vascular permeability (0 DPE), and VEGF expression was quantified at 5
      DPE to support that angiogenesis had occurred. CD31 staining was used to assess
      capillary density at both time points. RESULTS: [UCA] was a significant parameter
      for determining EBD leakage (permeability) and VEGF expression (p < 0.001 for
      both). However, [UCA] was not a significant parameter for capillary density at 0
      or 5 DPE. Multiple comparisons between 0 and 5 DPE showed that only 10* [UCA] at
      5 DPE was significantly different than 0 DPE, suggesting a [UCA] dependence of
      the angiogenic response. CONCLUSIONS: This study suggests that [UCA] was a
      significant parameter in the induction of an angiogenic response with US and
      UCAs. It also suggests that rather than damage from US and UCAs, as previously
      speculated, a nondestructive mechanical interaction between the UCAs and vascular
      endothelium induces bioeffects to potentiate the angiogenic response.

PMID- 22587915
TI  - Expression of BMP-2 and Ets1 in BMP-2-stimulated mouse pre-osteoblast
      differentiation is regulated by microRNA-370.
AB  - MicroRNAs (miRs) regulate several biological functions such as cell growth, cell
      differentiation, and carcinogenesis, by binding to the 3'-untranslated regions
      (3'-UTR) of specific target genes, in order to repress translation or promote
      degradation of the transcribed mRNAs. In the present study, using microRNA array
      and in silico analyses, we found that miR-370 regulates the expression of bone
      morphogenetic protein-2 (BMP-2) and V-ets Erythroblastosis Virus E26 Oncogene
      Homolog 1 (Ets1) in BMP-2-stimulated murine pre-osteoblast MC3T3-E1 cell
      differentiation. The enforced expression of mature miR-370 in MC3T3-E1 cells or
      primary osteoblast cells remarkably attenuated BMP-2-induced pre-osteoblast
      differentiation. To ascertain the mechanisms underlying the regulation of
      osteoblast differentiation by miR-370, we hypothesized a BMP-2-Ets1-PTHrP feed
      forward loop regulatory mechanism.

PMID- 22587917
TI  - [No sedation: dream or nightmare?].

PMID- 22587916
TI  - Use of the University of Minnesota Biocatalysis/Biodegradation Database for study
      of microbial degradation.
AB  - Microorganisms are ubiquitous on earth and have diverse metabolic transformative
      capabilities important for environmental biodegradation of chemicals that helps
      maintain ecosystem and human health. Microbial biodegradative metabolism is the
      main focus of the University of Minnesota Biocatalysis/Biodegradation Database
      (UM-BBD). UM-BBD data has also been used to develop a computational metabolic
      pathway prediction system that can be applied to chemicals for which
      biodegradation data is currently lacking. The UM-Pathway Prediction System (UM
      PPS) relies on metabolic rules that are based on organic functional groups and
      predicts plausible biodegradative metabolism. The predictions are useful to
      environmental chemists that look for metabolic intermediates, for regulators
      looking for potential toxic products, for microbiologists seeking to understand
      microbial biodegradation, and others with a wide-range of interests.

PMID- 22587919
TI  - [Changes in serum high mobility group box-1 protein and high-sensitivity C
      reactive protein in patients with acute cerebral infarction and their clinical
      significance].
AB  - OBJECTIVE: To study the potential role of high mobility group box-1 protein
      (HMGB1) and high-sensitivity C-reactive protein (hs-CRP) in acute cerebral
      infarction (ACI). METHODS: Forty patients with ACI were enrolled within 72 hours
      after onset of symptom in this study. Venous blood samples were collected within
      24 hours of admission, 7th day and 12th day after admission. Serum HMGB1 and hs
      CRP levels were measured with enzyme linked immunosorbent assay (ELISA) method.
      RESULTS: Serum HMGB1 levels (MUg/L) at all time points (24 hours: 7.598+/-0.280,
      7th day: 10.491+/-0.512, 12th day: 5.315+/-0.224) were significantly higher than
      those of healthy controls (n=20, 2.994+/-0.243) and risk factor group in which
      patients suffered from one risk factor in hypertension, diabetes mellitus, and
      hyperlipemia at least (n=20, 3.272+/-0.285), with significant difference (all
      P<0.01). Serum hs-CRP levels (mg/L, 24 hours: 5.815+/-0.408, 7th day: 5.063+/
      0.510, 12th day: 2.863+/-0.297) of the patients were also significantly higher
      than those of healthy controls (0.642+/-0.047), with significant difference (all
      P<0.01), and serum hs-CRP levels on 12th day were similar to that in risk factor
      group (2.514+/-0.312), with no significant difference (P>0.05). Serum HMGB1
      levels in risk factor group were higher than those in healthy control group but
      with no significant difference (P>0.05), and serum hs-CRP levels were
      significantly higher than those in healthy control group (P<0.01). The levels of
      HMGB1 and hs-CRP in serum were similar between patients with cerebral infarction
      in vertebral basilar system (n=17) and internal carotid artery system (n=23), and
      the result showed that the serum HMGB1 or hs-CRP levels had no correlation with
      infarct site, but had significantly positive correlations with the National
      Institute of Health stroke scale (NIHSS) score [r1=0.377, P1=0.034; r2=0.353,
      P2=0.025]. In addition, there was a positive correlation between levels of serum
      HMGB1 and hs-CRP (r=0.428, P=0.047). CONCLUSIONS; Inflammatory mediators
      including HMGB1 and hs-CRP might play important roles in the pathogenesis of ACI.
      They were positively correlated with the severity of ACI, while not correlated
      with infarct sites. Serum hs-CRP levels in ACI could be of value in early
      diagnosing of cerebral infarction. Serial determination of serum HMGB1 and hs-CRP
      levels might be helpful to evaluate the severity and prognosis of ACI.

PMID- 22587918
TI  - [Analysis of energy balance and risk factors on clinical outcomes in patients
      with severe traumatic brain injury].
AB  - OBJECTIVE: To observe the energy expenditure in severe traumatic brain injury
      patients, and to assess the impact of cumulative energy balance on clinical
      outcomes. METHODS: Using prospective self-controlled study, the change in energy
      expenditure of 42 patients with severe traumatic brain injury was measured by
      indirect calorimetry (IC). Daily energy intake was recorded. Afterwards, energy
      balance was calculated. The levels of nutritional biochemical indicators were
      compared. Logistic regression analysis was used to analyze the correlation of
      cumulative energy balance with clinical outcomes. RESULTS: Mean practical energy
      intake of all patients was (6787 +/- 1848) kJ/d, and mean negative energy balance
      was (913 +/- 285) kJ/d. The negative energy balance was most crucial in first 3
      days after admission. Meanwhile, practical energy intake was significantly lower
      than target energy intake (kJ: 2859 +/- 1370 vs. 6027 +/- 899, P < 0.01). The
      practical energy intake was increased with time, and it was found that the first
      14 days were crucial for development of negative energy balance. On 7th day after
      admission, albumin (g/L) level in plasma was lowest compared with that on 3rd day
      (29.5 +/- 5.0 vs. 35.9 +/- 3.8, P < 0.01), and then it was increased gradually
      returning to normal level on 28 days (34.1 +/- 2.8). Three days after admission,
      prealbumin (mg/L: 122.5 +/- 23.3) was obviously lower than normal level, but it
      rapidly elevated on 7th day (214.3 +/- 38.6, P < 0.01) and continued to rise till
      28th day (257.7 +/- 25.2). On the 3rd day after admission, C-reactive protein
      (mg/L: 139.5 +/- 54.4) was obviously higher than normal level. However, it
      significantly fell on 7th day (108.4 +/- 42.2, P < 0.01), and it continued to
      fall. Logistic regression analysis showed a strong association of cumulative
      negative energy balance with infection and upper gastrointestinal bleeding [odds
      ratio (OR) of infection was 2.130, 95% confidence interval (95%CI) 1.540 to
      29.661, P = 0.023; OR of upper gastrointestinal bleeding was 0.083, 95%CI 0.013
      to 0.542, P = 0.009]. CONCLUSIONS: Cumulative negative energy balance may be
      correlated with the occurrence of complications in patients with severe traumatic
      brain injury. On the basis of the measurements of changes in energy by IC, early
      supply of sufficient energy may improve the outcome of patients.

PMID- 22587920
TI  - [The diagnostic and prognostic values of serum total RNA concentration in
      patients with sepsis].
AB  - OBJECTIVE: To explore the diagnostic and prognostic roles of serum total RNA in
      patients with sepsis. METHODS: Seventy-six patients with sepsis admitted to
      intensive care unit (ICU) of Chinese PLA General Hospital from October 2009 to
      November 2010 were enrolled. Blood samples were drawn from these patients and
      total RNAs of these blood samples were isolated. The concentration of total RNA
      in the samples was detected. C-reactive protein (CRP) was determined by
      scattering turbidimetry, and procalcitonin (PCT) was determined using enzyme
      linked fluorescence analysis (ELFA). Acute physiology and chronic health
      evaluation II (APACHE II ) score and sequential organ failure assessment (SOFA)
      score were recorded. Twenty-four healthy individuals with matched age and sex
      were enrolled as normal controls. Receiver operating characteristic curve (ROC
      curve) was used to determine the optimal concentration of serum total RNA for the
      diagnosis of sepsis. Binary logistic regression analysis was used to analyze the
      risk factors of sepsis patients. RESULTS: The concentration of serum total RNA
      (ng/MUl) in sepsis group was significantly higher than healthy controls [4.233
      (0.204, 37.733) vs. 1.593 (0.319, 5.913), P<0.01]. The area under curve (AUC) of
      the diagnosis of sepsis was 0.820. When the cut-off point was set at 2.027
      ng/MUl, the concentration of serum total RNA yielded a sensitivity of 95.9% and a
      specificity of 65.2%. Total RNA concentration in the healthy controls, the
      survival group (n=42) and non-survival group (n=34) were step wisely increased
      [1.593 (0.319, 5.913), 4.178 (0.204, 10.776), 5.006 (0.997, 37.733),
      respectively, F=8.061, P=0.001]. Binary multivariate logistic regression analysis
      showed that APACHE II score and SOFA score were independent risk factors of
      septic patients [APACHE II score: odds ratio (OR)=1.265, 95% confidence interval
      (95%CI) 1.031 to 1.553, P=0.025; SOFA score: OR=1.151, 95%CI 1.031 to 2.284,
      P=0.012]. But PCT was not independent risk factor of sepsis patients (OR=1.075,
      95%CI 0.974 to 1.187, P=0.151). In the binary univariate logistic regression
      analysis model, the OR of total RNAs was 1.149, but P value was 0.061, because of
      the small sample size. CONCLUSIONS: The concentration of total RNA in sepsis
      patients' serum was significantly increased and correlated to the severity of
      sepsis, which can be used as biomarkers for sepsis patients.

PMID- 22587921
TI  - [Risk factors analysis of outcomes for patients with primary pontine hemorrhage].
AB  - OBJECTIVE: To evaluate the risk factors of prognosis in patients with primary
      pontine hemorrhage. METHODS: A retrospective analysis was conducted using data
      from 60 patients admitted with a diagnosis of primary pontine hemorrhage to the
      Department of Neurology of Nanfang Hospital in Guangzhou City. Patients were
      classified as survivors (n=34) and non-survivors (n=26) according to their
      outcomes on 30 days from the onset of symptoms. Univariate analysis and
      multivariate logistic regression analysis were performed on clinical data and
      imaging features of patients. Receiver operating characteristic curve (ROC curve)
      analysis was used on continuous parameters verified by multivariate logistic
      regression analysis to determine their cut-off value. RESULTS: The 30-day
      mortality was 43.3% for 60 patients with primary pontine hemorrhage. Univariate
      analysis showed Glasgow coma scale (GCS) at admission, temperature, heart rate,
      hemorrhage volume, mechanical ventilation, involvement of ventricles and location
      of hematoma were statistically related to 30-day mortality in patients with
      primary pontine hemorrhage. Multivariate logistic regression analysis
      demonstrated that the GCS at admission [odds ratio (OR)=0.745, 95% confidence
      interval (95%CI) 0.585 to 0.949], hemorrhage volume (OR=1.438, 95%CI 1.077 to
      1.919) and location of hematoma (basal-tegmental hemorrhage, OR=0.120, 95%CI
      0.016 to 0.904) were independent risk factors of poor prognosis in patients with
      primary pontine hemorrhage (all P<0.05). ROC curve analysis showed the cut-off
      value for GCS score at admission and hemorrhage volume was 7.5 and 5.5 ml,
      respectively. CONCLUSION: Patients suffering from primary pontine hemorrhage in
      the basal-tegmental region, GCS<7.5 at admission and hemorrhage volume>=5.5 ml
      would lead to a poor outcome in 30 days.

PMID- 22587922
TI  - [Protective effects of heparin against increased permeability of endothelial
      cells induced by lipopolysaccharide].
AB  - OBJECTIVE: To evaluate the effects of heparin on the changes in permeability and
      cytoskeleton of cultured human umbilical vascular endothelial cells (HUVECs)
      induced by lipopolysaccharide (LPS). METHODS: HUVECs were cultured in vitro and
      randomly assigned to blank control group, LPS group, heparin group, and LPS +
      heparin group, n=8. Cell viability was determined by methyl thiazolyl tetrazolium
      (MTT) method. Endothelial permeability was measured with the Transwell chamber
      models. F-actin of cytoskeletons was assayed with fluorescein isothiocyanate
      (FITC)-phalloidine. RESULTS: Compared with the blank control group, 10 mg/L and
      100 mg/L of LPS significantly inhibited cell viability (0.695+/-0.015, 0.476+/
      0.030 vs. 0.860+/-0.053, P<0.05 and P<0.01). Heparin 100 kU/L also inhibited cell
      viability (0.675+/-0.030 vs. 0.840+/-0.023, P<0.05). Increase in permeability of
      endothelium was induced by 10 mg/L of LPS, and it peaked at 4 hours, there was
      significant difference compared with blank control group (5.882+/-0.101 vs.
      4.489+/-0.015, P<0.05). At the same time, LPS led to the reorganization of F
      actin cytoskeleton and the formation of stress fibers. LPS+heparin decreased the
      increase in permeability of endothelium at 2-12 hours (2 hours: 4.382+/-0.053 vs.
      5.084+/-0.129, 4 hours: 4.528+/-0.044 vs. 5.882+/-0.101, 6 hours: 4.381+/-0.089
      vs. 5.479+/-0.125, 12 hours: 4.447+/-0.054 vs. 4.719+/-0.080, all P<0.05), and
      attenuated the reorganization of F-actin and the formation of stress fibers.
      CONCLUSION: Heparin attenuates LPS-induced increase in permeability of HUVECs and
      alterations in F-actin organization, thus protects endothelial barrier.

PMID- 22587923
TI  - [The influence of positive end-expiratory pressure on central venous pressure in
      patients with severe craniocerebral injury].
AB  - OBJECTIVE: To observe the impact of positive end-expiratory pressure (PEEP) on
      central venous pressure (CVP) in mechanically ventilated patients with severe
      craniocerebral injury. METHODS: A prospective, interventional, self-control study
      was conducted. Thirty severe craniocerebral injury patients with central
      respiratory failure were enrolled. The changes in CVP, mean arterial pressure
      (MAP), heart rate (HR) and pulse oxygen saturation [SpO2] were monitored at
      different PEEP levels [0, 3, 6, 9, 12, 15 cm H2O; 1 cm H2O=0.098 kPa] during
      mechanical ventilation and after weaning of mechanical ventilation. The
      influences of PEEP and its discontinuance on haemodynamics and oxygenation were
      analyzed. RESULTS: The values of CVP [cm H2O] were increased when PEEP increased
      (from 7.9+/-3.1 to 13.1+/-3.7), a linear correlation was found (R=0.509,
      P=0.000), and linear regression equation was CVP [cm H2O]=7.774+0.368*PEEP [cm
      H2O]; CVP was elevated about 0.368 cm H2O when PEEP increased 1 cm H2O. CVP
      values significantly decreased during discontinuance of mechanical ventilation,
      as compared to those measured at different PEEP levels during mechanical
      ventilation (F=24.429, P=0.000). The values of MAP, HR and SpO2 showed no
      significant change with increase of PEEP levels [MAP (mm Hg, 1 mm Hg=0.133 kPa):
      from 81.6+/-10.4 to 85.6+/-10.6; HR (beats per minute): from 79.9+/-13.5 to
      88.1+/-15.4; SpO2: from 0.968+/-0.036 to 0.975+/-0.033, all P>0.05] in
      mechanically ventilated patients, but discontinuance of mechanical ventilation
      could significantly increase the levels of MAP and HR (95.3+/-8.4 and 94.9+/
      10.3, respectively) and lower SpO2 levels (0.928+/-0.036, all P=0.000).
      CONCLUSIONS: CVP values were overestimated during an increase in PEEP in
      mechanically ventilated patients with severe craniocerebral injury. CVP was
      increased about 0.368 cm H2O following an increase of PEEP of 1 cm H2O, whereas
      the values of MAP, HR and SpO2 showed no significant change with increase in PEEP
      levels. This study could offer a theoretical base in the correct assessment of
      CVP values at different PEEP levels without discontinuation of mechanical
      ventilation.

PMID- 22587924
TI  - [Neuroprotective effects of combined pretreatment with edaravone and propofol on
      neonatal rat cerebral cortical neurons with ischemia/reperfusion injury in
      vitro].
AB  - OBJECTIVE: To investigate the protective effect of combined pretreatment of
      edaravone and propofol on cerebral cortex with ischemia/reperfusion (I/R) injury
      and its therapeutic window. METHODS: Sprague Dawley (SD) rat brain cortex cells
      harvested within 24 hours of birth were cultured in vitro for 7 days. The cells
      were then divided into blank control group, glutamate injury group, 24-hour drug
      precondition control group, and 24-, 2-, 0-hour drug precondition groups
      according to random number table. The nerve cells in each pretreatment group were
      cultured in medium containing 100 MUmol/L of edaravone and 3 mg/L of propofol 24,
      2, or 0 hour before glutamate damage (200 MUmol/L for 0.5 hour). Nerve cell
      survival or damage was determined by methyl thiazolyl tetrazolium (MTT), lactate
      dehydrogenase (LDH) leakage rate, and nerve cell Na+-K+-ATPase activity. The
      oxidation and anti-oxidation ability of nerve cells was observed by determining
      superoxide dismutase (SOD) activity (xanthine oxidase), malondialdehyde (MDA)
      content (thiobarbituric acid). Nerve apoptosis was detected by flow cytometry.
      RESULTS: Compared with blank control group, in the glutamate injury group, nerve
      cell survival rate [(62.2+/-23.4)% vs. (90.5+/-14.8)%], the activity of SOD
      (U/ml: 6.864+/-2.872 vs. 29.569+/-3.684), Na+-K+-ATPase activity [U*mg(-1)*h(-1):
      0.318+/-0.146 vs. 0.636+/-0.168] were significantly decreased, and rate of
      neuronal apoptosis [(9.4+/-0.7)% vs. (6.1+/-0.2)%], the content of MDA (nmol/ml:
      0.515+/-0.101 vs. 0.294+/-0.105), LDH leakage rate [(41.2+/-1.6)% vs. (36.8+/
      4.6)%] were significantly increased (P<0.05 or P<0.01). Compared with glutamate
      injury group, the cell survival rate and the activity of SOD and Na+-K+-ATPase
      were significantly increased in the drug pretreatment groups, and apoptosis rate,
      MDA content, and LDH leakage rate were significantly decreased with time
      department, and effect in the 24-hour pretreatment group was most significant
      [survival rate of cell: (89.2+/-30.3)% vs. (62.2+/-23.4)%, SOD activity (U/ml):
      17.780+/-4.514 vs. 6.864+/-2.872, Na+-K+-ATPase activity [U*mg(-1)*h(-1)]:
      0.541+/-0.052 vs. 0.318+/-0.146, the rate of cell apoptosis: (6.7+/-0.4)% vs.
      (9.4+/-0.7)%, the content of MDA (nmol/ml): 0.319+/-0.101 vs. 0.515+/-0.101, LDH
      leakage rate: (37.2+/-1.4)% vs. (41.2+/-1.6)%, all P<0.01]. CONCLUSION: The
      synergistic protective effect of pretreatment with edaravone combined with
      propofol on neonatal rat brain cortex cells with I/R injury in vitro was evident;
      and 24-hour pretreatment is the best time window of protection for the cerebral
      neurons.

PMID- 22587925
TI  - [A controlled study on the treatment of acute progressive cerebral infarction by
      continuous anticoagulation with small doses of heparin].
AB  - OBJECTIVE: To discuss the treatment of acute progressive cerebral infarction by
      continuous anticoagulation with small doses of heparin. METHODS: A prospective,
      randomized, and controlled clinical research was conducted. Three hundred and
      fifty-one patients were randomly divided into three groups. Group A (n=119) was
      treated with heparin, which was controlled by an infusion pump with a speed of 18
      U*kg(-1)*h(-1) for 24 hours, and the dosage was regulated according to the
      changes in activated partial thromboplastin time (APTT) which was determined
      every 8 hours. Group B (n=115) was treated with intravenous drip of 12,500 U of
      heparin with a speed of 18 U*kg(-1)*h(-1) once a day. Group C (n=117) was treated
      with 5000 U of low-molecular-weight heparin calcium injection twice a day. After
      14 days, nerve function defect according to the National Institutes of Heath
      stroke scale (NIHSS) score was determined, the adverse events (e.g. intracranial
      hemorrhage, subcutaneous ecchymosis, gingival bleeding, hematuria and occult
      blood in stools) were observed. After 6 months, the recurrence rate and Barthel
      index (BI) would be determined. RESULTS: The total efficiency in group A (95.80%)
      was significantly higher than that in group B (85.22%) and group C (85.47%).
      Recurrence rate in group A (1.68%) was significantly lower than group B (8.70%)
      and group C (8.33%) with significant differences (P<0.05 or P<0.01), while there
      was no significant difference between group B and group C (both P>0.05). The BI
      of group A (89.27+/-8.56) was significantly higher than group B (72.57+/-9.77)
      and group C (71.66+/-9.37) with significant difference (both P<0.01), while there
      was no significant difference between group B and group C (P>0.05). Adverse event
      rate in group A (5.88%) was slightly higher than that of group B (3.48%) and
      group C (4.27%), but the difference was not significant (both P>0.05).
      CONCLUSIONS: Continuous infusion of low dosage of heparin could significantly
      reduce neurologic impairment score in patients with progressive cerebral
      infarction, increase cure rate, reduce the recurrence rate, and raise the BI of
      patients, and it dose not increase the risk of intracranial and extracranial
      hemorrhage.

PMID- 22587926
TI  - [Significance of serum procalcitonin levels in the evaluation of severity and
      prognosis of patients with systemic inflammatory response syndrome].
AB  - OBJECTIVE: To observe the dynamic changes in serum procalcitonin (PCT), C
      reactive protein (CRP), and white blood cell (WBC) count in systemic inflammatory
      response syndrome (SIRS) and their implication in assessment of illness severity
      and prognosis. METHODS: A prospective case control study was conducted. Seventy
      two patients with SIRS in Guangdong General Hospital were enrolled in intensive
      care unit (ICU) from May, 2010 to June, 2011. Parameters including PCT, CRP, and
      WBC count were determined on the 1st, 3rd, and 5th day after admission. The
      patients were divided into septic group (n=49) and non-septic group (non
      infectious SIRS group, n=23) according to the presence or absence of infectious.
      Dynamic changes in all parameters were compared between the two groups and
      correlation analysis was carried out on the basis of differential indexes and
      sequential organ failure assessment (SOFA). The clinical outcome within 28 days
      after admission to ICU was observed, and the patients were divided into death
      group (n=19) and survival group (n=53). Dynamic changes in all parameters between
      the two groups were compared. Relevant parameters were analyzed with area under
      receiver operator characteristic curve (ROC curve, AUC) to predict 28-day
      survival. Logistic regression analysis of the multiple factors was used to screen
      independent risk factors for predicting death. RESULTS: PCT level (MUg/L) on 1st,
      3rd, 5th day after admission were all significantly higher in septic group than
      those in non-septic group (1st day: 2.5+/-0.3 vs. 0.9+/-0.2, 3rd day: 1.9+/-0.3
      vs. 0.6+/-0.2, 5th day: 0.9+/-0.1 vs. 0.5+/-0.1, all P<0.05), while there was no
      statistically significant difference in CRP and WBC between two groups. PCT level
      in septic group was gradually decreased with time, there were statistically
      significant differences between septic group and non-septic group at the
      different treatment time (all P<0.05), but there was no correlation between PCT
      and treatment duration in non-septic group. Positive statistical correlation was
      found between PCT and SOFA score (r=0.979, P<0.05). PCT (MUg/L) and CRP levels
      (mg/L) on 1st, 3rd, 5th day were significantly higher in death group than those
      of survival group (PCT on 1st day: 2.0+/-0.8 vs. 0.8+/-0.3, 3rd day: 2.2+/-0.7
      vs. 0.6+/-0.3, 5th day: 2.4+/-1.0 vs. 0.4+/-0.1; CRP on 1st day: 422+/-45 vs.
      411+/-44, 3rd day: 418+/-39 vs. 403+/-52, 5th day: 392+/-38 vs. 382+/-46, all
      P<0.05), but WBC count showed no statistically significant difference between two
      groups. PCT level in survival group showed a significant lowering along with
      treatment duration, and statistical difference was seen by paired comparison
      between every two time-points (all P<0.05). There was no correlation between PCT
      level and treatment duration in death group, and it maintained a rather high
      level. No significant difference was seen in CRP and WBC between two groups with
      passage of time. AUC was 0.824 and 0.720, respectively, when patient's 28-day
      survival was predicted by PCT and CRP (both P<0.01). Logistic regression analysis
      of the multiple factors revealed that PCT>2.23 MUg/L was independent risk factor
      predicting the prognosis [odds ratio (OR) was 1.773, 95% confidence interval
      (95%CI) 1.033 to 3.214, P=0.015]. CONCLUSIONS: Serum PCT evaluation may be
      helpful in differentiating sepsis and non-sepsis at early stage of disease, and
      also in predicting the severity of the illness and prognosis of SIRS. PCT may be
      one of the independent risk factors for 28-day survival.

PMID- 22587927
TI  - [Value of procalcitonin in the early diagnosis of sepsis in Department of
      Emergency].
AB  - OBJECTIVE: To investigate the value of procalcitonin (PCT) in the early diagnosis
      and risk stratification in sepsis. METHODS: Among 90 patients, 42 patients
      suffered sepsis, and 48 patients with severe sepsis. Serum PCT levels, high
      sensitivity C-reactive protein (hs-CRP), white blood cell (WBC) count, the
      percentage of neutrophils and lactate levels in sepsis and severe sepsis patients
      were determined. Receive operating characteristic curve (ROC curve) was drawn to
      evaluate the ability of PCT and related inflammatory parameters in assessing risk
      factors in patients with sepsis, and to analyze correlation between PCT and
      sequential organ failure assess (SOFA) score, WBC, lactic acid, and hs-CRP.
      RESULTS: Compared with sepsis patients, among severe sepsis patients, the levels
      of PCT (MUg/L), hs-CRP (mg/L), WBC [*10(9)/L] , and SOFA score were significantly
      higher (PCT: 7.228+/-2.153 vs. 0.172+/-0.165, hs-CRP: 102.68+/-90.99 vs. 29.05+/
      28.76, WBC: 14.15+/-8.14 vs. 8.15+/-4.55, SOFA score: 9.87+/-2.47 vs. 3.09+/
      1.55), with statistical significance (all P<0.01), and the levels of percentage
      of neutrophils and lactic acid (mmol/L) were slightly increased (percentage of
      neutrophils: 0.820+/-0.094 vs. 0.740+/-0.130, lactic acid: 1.47+/-0.99 vs. 1.18+/
      0.60), with no statistical significance (both P>0.05). Analysis of ROC curve
      displayed that area under the curve (AUC) of PCT was 0.808, which was higher than
      that of WBC, percentage of neutrophils, lactic acid and hs-CRP (AUC was 0.124,
      0.042, 0.551 and 0.262, respectively), and when PCT was 1.000 MUg/L, the
      sensitivity was 80.3%, specificity was 72.2%, and they were better than those of
      other traditional markers of inflammation. Bivariate correlation analysis showed
      that a positive correlation was found between PCT and SOFA score and WBC
      [r1=0.418, P1=0.006; r2=0.251, P2=0.011], and there was no correlation between
      PCT and lactic acid and hs-CRP [r1=0.186, P1=0.155; r2=0.089, P2=0.133].
      CONCLUSION: Serum PCT is a reliable measure in emergency room for early diagnosis
      of sepsis with high sensitivity and specificity, it could be used as a routine
      monitoring index in critically ill patients to help assess disease severity in
      sepsis.

PMID- 22587928
TI  - [An experimental study of contrast enhanced ultrasound diagnosis of cerebral
      intraparenchymal hemorrhage in dogs].
AB  - OBJECTIVE: To explore the role of contrast enhanced ultrasound (CEUS) in
      diagnosing experimental cerebral intraparenchymal hemorrhage (IH) in dogs.
      METHODS: A self-control study was conducted. An IH model was reproduced by
      puncturing middle cerebral artery (MCA) in 12 dogs. Two-dimensional ultrasound
      and CEUS were conducted immediately, 30 minutes, and 1 hour after modeling,
      respectively, to observe the lesion echo and bleeding area. CT scans were also
      conducted at 1 hour after modeling, then the lesion size in CT scan was compared
      with that of CEUS. RESULTS: In 12 dogs IH model was reproduced successfully, and
      unilateral hematomas were confirmed by CT and pathological examination. Two
      dimensional ultrasound of IH showed irregular high-echo area, with unclear
      boundary, but it was not able to show active bleeding. CEUS demonstrated active
      bleeding by outflow and pooling of contrast agent with obvious enhancement. CEUS
      of the hematoma showed perfusion deficit, with a clear boundary. The size of
      bleeding lesions (cm) continued to increase at 30 minutes and 1 hour after
      modeling (1.47+/-0.40, 1.76+/-0.45 by CEUS measuring), and demonstrated
      statistically significant difference comparing with the measurement of IH
      immediately after modeling (1.03+/-0.24, both P<0.01), while there was no
      statistically significant difference between the 30-minute and 1-hour
      measurements (P>0.05). Compared with the measurements between CEUS and CT at 1
      hour, there was no statistically significant difference in size of bleeding
      lesions (1.76+/-0.45 vs. 1.79+/-0.47, P>0.05). CONCLUSION: CEUS can help
      determine the extent and size of IH, and the process of hematoma formation when
      dynamically monitoring.

PMID- 22587929
TI  - [Evaluation of the sedative effect of dexmedetomidine on patients after surgical
      occlusion of ruptured cerebral aneurysm in intensive care unit].

PMID- 22587930
TI  - [Prognostic effects of serum albumin level in patients with progressive stroke].

PMID- 22587931
TI  - Evaluation and optimization of multiple fluorophore analysis of a Pseudomonas
      aeruginosa biofilm.
AB  - Conventional laser scanning microscopy for multiple fluorescent stains can be a
      useful tool if the problems of autofluorescence and cross-talk are eliminated.
      The technique of spectral imaging was employed to unmix five different
      fluorophores - ranging in emission from 435 to 665 nm - applied to a Pseudomonas
      aeruginosa biofilm with overlapping spectra and which was not possible using
      traditional channel mode operation. Using lambda scanning and linear unmixing,
      the five fluorophores could be distinguished with regions of differentiation
      apparent.

PMID- 22587932
TI  - Detection and identification of methicillin resistant and sensitive strains of
      Staphylococcus aureus using tandem measurements.
AB  - Discrimination of methicillin resistant (MRSA) and sensitive (MSSA) strains of
      Staphylococcus aureus, was achieved by the specially selected lytic bacteriophage
      with a wide host range of S. aureus strains and a penicillin-binding protein (PBP
      2a) specific antibody. A quartz crystal microbalance with dissipation monitoring
      (QCM-D) was employed to analyze bacteria-phage interactions. The lytic phages
      were transformed into phage spheroids by exposure to water-chloroform interface.
      Phage spheroid monolayers were transferred onto QCM-D sensors by Langmuir
      Blodgett (LB) technique. Biosensors were tested in the flow mode with bacterial
      water suspensions, while collecting frequency and energy dissipation changes.
      Bacteria-spheroid interactions resulted in decreased resonance frequency and an
      increase in dissipation energy for both MRSA and MSSA strains. Following the
      bacterial binding, these sensors were further exposed to a flow of the penicillin
      binding protein (PBP 2a) specific antibody conjugated latex beads. Sensors tested
      with MRSA responded to PBP 2a antibody beads; while sensors examined with MSSA
      gave no response. This experimental difference establishes an unambiguous
      discrimination between methicillin resistant and sensitive S. aureus strains.
      Both free and immobilized bacteriophages strongly inhibit bacterial growth on
      solid/air interfaces and in water suspensions. After lytic phages are transformed
      into spheroids, they retain their strong lytic activity and demonstrate high
      bacterial capture efficiency. The phage and phage spheroids can be used for
      screening and disinfection of antibiotic resistant bacteria. Other applications
      may include use on biosensors, bacteriophage therapy, and antimicrobial surfaces.

PMID- 22587933
TI  - Prospective systematic review registration: perspective from the Guidelines
      International Network (G-I-N).
AB  - Clinical practice and public health guidelines are important tools for
      translating research findings into practice with the aim of assisting health
      practitioners as well as patients and consumers in health behavior and healthcare
      decision-making. Numerous programs for guideline development exist around the
      world, with growing international collaboration to improve their quality. One of
      the key features in developing trustworthy guidelines is that recommendations
      should be based on high-quality systematic reviews of the best available
      evidence. The review process used by guideline developers to identify and grade
      relevant evidence for developing recommendations should be systematic,
      transparent and unbiased. In this paper, we provide an overview of current
      international developments in the field of practice guidelines and methods to
      develop guidelines, with a specific focus on the role of systematic reviews. The
      Guidelines International Network (G-I-N) aims to stimulate collaboration between
      guideline developers and systematic reviewers to optimize the use of available
      evidence in guideline development and to increase efficiency in the guideline
      development process. Considering the significant benefit of systematic reviews
      for the guideline community, the G-I-N Board of Trustees supports the
      international prospective register of systematic reviews (PROSPERO) initiative. G
      I-N also recently launched a Data Extraction Resource (GINDER) to present and
      share data extracted from individual studies in a standardized template. PROSPERO
      and GINDER are complementary tools to enhance collaboration between guideline
      developers and systematic reviewers to allow for alignment of activities and a
      reduction in duplication of effort.

PMID- 22587934
TI  - The effects of sage extract feed supplementation on biochemical parameters,
      weight of internal organs and Salmonella counts in chickens.
AB  - We investigated the effects of dietary addition of sage extract on the
      biochemical parameters, weight of some body organs and changes in the counts of
      Salmonella Enteritidis PT4 (SE) in experimentally infected chickens. The
      following diets were used: basal diet, basal diet with addition of an extract of
      Salvia officinalis L. (S), basal diet and SE, and basal diet and S and SE (SSE).
      Compared to the SE group, sage extract in the SSE group decreased activities of
      ALP and ALT and concentrations of glucose and bilirubin on the 4th day post
      inoculation (p.i.). However, on the 18th day p.i., lower levels of bilirubin and
      ALT activity only were detected. Addition of sage extract to the diets decreased
      the counts of Salmonella in the liver, spleen and caecum at both sampling times,
      along with lower production of mucus in the chickens' intestines. Our results
      suggest that the addition of sage extract to the diet could be effective in
      protecting SE-infected chickens.

PMID- 22587936
TI  - On the role of the microenvironment in mammary gland development and cancer.

PMID- 22587937
TI  - Safety immunopharmacology: evaluation of the adverse potential of pharmaceuticals
      on the immune system.
AB  - The ICH S6R1 and S8 guidelines define a general framework for the immunotoxicity
      evaluation of biotechnology-derived pharmaceuticals and human pharmaceuticals,
      respectively. As severe and unpredicted adverse events dramatically showed in the
      recent years that the immune system is a critical aspect of drug safety, this
      framework needs to be revisited to enhance the prediction of nonclinical immune
      safety evaluation. Safety immunopharmacology is deemed to contribute to this
      awaited improvement by enabling early screening of the potential for drug
      candidates to induce unexpected immunosuppressive and immunostimulatory effects
      as well as nonimmune-mediated hypersensitivity reactions. Dedicated safety
      immunopharmacology can also generate mechanistic data to determine which relevant
      additional immunotoxicity studies should be conducted. Immunological assays and
      models that can be considered for use in the context of safety pharmacology
      studies are presented as well as perspectives for their timely development.

PMID- 22587935
TI  - Deconstructing pancreas developmental biology.
AB  - The relentless nature and increasing prevalence of human pancreatic diseases, in
      particular, diabetes mellitus and adenocarcinoma, has motivated further
      understanding of pancreas organogenesis. The pancreas is a multifunctional organ
      whose epithelial cells govern a diversity of physiologically vital endocrine and
      exocrine functions. The mechanisms governing the birth, differentiation,
      morphogenesis, growth, maturation, and maintenance of the endocrine and exocrine
      components in the pancreas have been discovered recently with increasing tempo.
      This includes recent studies unveiling mechanisms permitting unexpected
      flexibility in the developmental potential of immature and mature pancreatic cell
      subsets, including the ability to interconvert fates. In this article, we
      describe how classical cell biology, genetic analysis, lineage tracing, and
      embryological investigations are being complemented by powerful modern methods
      including epigenetic analysis, time-lapse imaging, and flow cytometry-based cell
      purification to dissect fundamental processes of pancreas development.

PMID- 22587938
TI  - Linear normalised hash function for clustering gene sequences and identifying
      reference sequences from multiple sequence alignments.
AB  - BACKGROUND: Comparative genomics has put additional demands on the assessment of
      similarity between sequences and their clustering as means for classification.
      However, defining the optimal number of clusters, cluster density and boundaries
      for sets of potentially related sequences of genes with variable degrees of
      polymorphism remains a significant challenge. The aim of this study was to
      develop a method that would identify the cluster centroids and the optimal number
      of clusters for a given sensitivity level and could work equally well for the
      different sequence datasets. RESULTS: A novel method that combines the linear
      mapping hash function and multiple sequence alignment (MSA) was developed. This
      method takes advantage of the already sorted by similarity sequences from the MSA
      output, and identifies the optimal number of clusters, clusters cut-offs, and
      clusters centroids that can represent reference gene vouchers for the different
      species. The linear mapping hash function can map an already ordered by
      similarity distance matrix to indices to reveal gaps in the values around which
      the optimal cut-offs of the different clusters can be identified. The method was
      evaluated using sets of closely related (16S rRNA gene sequences of Nocardia
      species) and highly variable (VP1 genomic region of Enterovirus 71) sequences and
      outperformed existing unsupervised machine learning clustering methods and
      dimensionality reduction methods. This method does not require prior knowledge of
      the number of clusters or the distance between clusters, handles clusters of
      different sizes and shapes, and scales linearly with the dataset. CONCLUSIONS:
      The combination of MSA with the linear mapping hash function is a computationally
      efficient way of gene sequence clustering and can be a valuable tool for the
      assessment of similarity, clustering of different microbial genomes, identifying
      reference sequences, and for the study of evolution of bacteria and viruses.

PMID- 22587939
TI  - Concurrent attenuated reactivity of alpha-amylase and cortisol is related to
      disruptive behavior in male adolescents.
AB  - Attenuated reactivity of salivary alpha-amylase has been proposed as a specific
      sympathetic marker of disruptive behavior in juveniles and may have additional
      value to studying other autonomic parameters and hypothalamic-pituitary-adrenal
      axis activity. Investigating the interrelationships between neurobiological
      parameters in relation to juvenile disruptive behavior may enhance insight into
      the complex mechanisms at play. We investigated salivary alpha-amylase, cortisol,
      heart rate (HR), and heart rate variability (HRV) in response to a standardized
      public speaking task, and examined interactions between these parameters in
      relation to disruptive behavior. Participants were 48 delinquent male adolescents
      (mean age 18.4 years, SD 0.9), with and without a disruptive behavior disorder
      (resp. DP+, DP-) and 16 matched normal controls (NC). A structured psychiatric
      interview as well as the Youth Self Report and Child Behavior Checklist were
      administered to assess disruptive behavior. Alpha-amylase and cortisol
      reactivity, but not HR or HRV, showed significant inverse associations with
      dimensional measures of disruptive behavior. Moreover, both cortisol and alpha
      amylase reactivity were significantly lower in the DP+ group as compared to the
      NC group. The mentioned relationships remained present when nicotine use was
      entered as a covariate. Combining alpha-amylase and cortisol in one model
      explained a larger part of the variance of disruptive behavior than either single
      parameter. There were no interactions between alpha-amylase and cortisol or HRV
      in relation to disruptive behavior. Attenuated alpha-amylase responsivity to
      stress is a correlate of disruptive behavior in late-adolescent males. Although
      nicotine use explains a considerable part of the variance of disruptive behavior,
      both alpha-amylase and cortisol are related to disruptive behavior, over and
      above the effect of nicotine use. Combining alpha-amylase and cortisol improved
      insight into neurobiological mechanisms involved with disruptive behavior;
      concurrent low reactivity of both parameters was related to higher levels of
      disruptive behavior.

PMID- 22587940
TI  - Estrogens, estrogen receptors, and female cognitive aging: the impact of timing.
AB  - Estrogens have been shown to be protective agents against neurodegeneration and
      associated cognitive decline in aging females. However, clinical data have been
      equivocal as to the benefits to the brain and cognition of estrogen therapy in
      postmenopausal women. One factor that is proposed to be critical in determining
      the efficacy of hormone therapy is the timing of its initiation. The critical
      period or window of opportunity hypothesis proposes that following long-term
      ovarian hormone deprivation, the brain and cognition become insensitive to
      exogenously administered estrogens. In contrast, if estrogens are administered
      during a critical period near the time of cessation of ovarian function, they
      will exert beneficial effects. The focus of the current review is the examination
      of evidence from rodent models investigating the critical period hypothesis. A
      growing body of experimental data indicates that beneficial effects of 17beta
      estradiol (estradiol) on cognition and on cholinergic function and hippocampal
      plasticity, both of which have been linked to the ability of estradiol to exert
      beneficial effects on cognition, are attenuated if estradiol is administered
      following a period of long-term ovarian hormone deprivation. Further, emerging
      data implicate loss of estrogen receptor alpha (ERalpha) in the brain resulting
      from long-term hormone deprivation as a basis for the existence of the critical
      period. A unifying model is proposed by which the presence or absence of
      estrogens during a critical period following the cessation of ovarian function
      permanently alters the system resulting in decreased or increased risk,
      respectively, of neurodegeneration and cognitive decline.

PMID- 22587941
TI  - Multifunctional drug delivery system for targeting tumor and its acidic
      microenvironment.
AB  - Effective targeting drug delivery for cancer therapy still remains a formidable
      challenge due to the complication and heterogeneity of malignant tumors. Herein,
      a multifunctional targeting strategy was proposed, in which a novel pH-sensitive
      polymethacrylates (PMA)-grafted poly(amidoamine) (PAMAM) nano delivery system was
      designed to be responsive to the acidic tumor microenvironment, and thereby
      trigger drug release in the intra-tumoral space. In addition, folate-PEGylation
      was applied to modify the surface of PMA-PAMAM nanoparticles in order to enhance
      tumor selectivity via both active and passive targeting mechanisms: folate
      receptor targeting, long circulation and EPR effect. The utility and efficacy of
      such system was demonstrated both in vitro and in vivo. Tumor drug accumulation
      was significantly enhanced by folate-PEGylated PMA-PAMAM nanoparticles, and such
      observation corresponded to their strong inhibition of tumor growth in tumor
      bearing mice, demonstrating the success of the multifunctional targeting
      delivery. This multifunctional targeting strategy provides a promising solution
      to improve targeting drug delivery for combating the complex cancer diseases.

PMID- 22587942
TI  - A methodological study to compare survey-based and observation-based evaluations
      of organisational and safety cultures and then compare both approaches with
      markers of the quality of care.
AB  - BACKGROUND: Patient safety concerns have focused attention on organisational and
      safety cultures, in turn directing attention to the measurement of organisational
      and safety climates. OBJECTIVES: First, to compare levels of agreement between
      survey- and observation-based measures of organisational and safety
      climates/cultures and to compare both measures with criterion-based audits of the
      quality of care, using evidence-based markers drawn from national care standards
      relating to six common clinical conditions. (This required development of an
      observation-based instrument.) Second, to examine whether observation-based
      evaluations could replace or augment survey measurements to mitigate concerns
      about declining response rates and increasing social desirability bias. Third, to
      examine mediating factors in safety and organisational climate scores. DESIGN:
      The study had three strands: (A) a postal questionnaire survey to elicit staff
      perceptions of organisational and safety climates, using six prevalidated scales;
      (B) semistructured non-participant observation of clinical teams; and (C) a
      retrospective criterion-based audit carried out by non-clinical auditors to
      minimise hindsight bias. Standardised summary scores were created for each
      strand, and pairs of measurements were compared (strand A with strand B, strand A
      with strand C, and strand B with strand C) using Bland-Altman plots to evaluate
      agreement. Correlations were also examined. Multilevel modelling of Strand A
      scores explored mediating factors. SETTING AND PARTICIPANTS: Eight emergency
      departments and eight maternity units in England, UK. INTERVENTIONS: None. MAIN
      OUTCOME MEASURES: Examination of feasibility, correlation and agreement. RESULTS:
      Strand A: the overall response rate was 27.6%, whereas site-specific rates ranged
      from 9% to 47%. We identified more mediating factors than previous studies;
      variable response rates had little effect on the results. Organisational and
      safety climate scores were strongly correlated (r = 0.845) and exhibited good
      agreement [standard deviation (SD) differences 0.449; 14 (88%) within +/- 0.5;
      one large difference]. Two commonly used scales had high levels of positive
      responses, suggesting positive climates or social desirability bias. Strand B:
      scoring on a four-point scale was feasible. Observational evaluation of teamwork
      culture was good but too limited for evaluating organisational culture. Strand C:
      a total of 359-399 cases were audited per condition. The results varied widely
      between different markers for the same condition, so selection matters. Each site
      performed well on some markers but not others, with few consistent patterns. Some
      national guidelines were contested. Comparisons: the comparison of safety climate
      (survey) and teamwork culture (observation) revealed a moderately low correlation
      (r = 0.316) and good agreement [SD differences 1.082; 7 (44%) within +/-0.5; one
      large difference]. The comparison of safety climate (survey) and performance
      (audit) revealed lower correlation (r = 0.150, i.e. relationship not linear) but
      reasonably good agreement [SD differences 0.992; 9 (56%) within +/- 0.5; two
      large differences]. Comparisons between performance (audit) and both
      organisational climate (survey) and teamwork culture (observation) showed
      negligible correlations (< 0.1) but moderately good agreement [SD differences
      1.058 and 1.241; 6 (38%) and 7 (44%) within +/- 0.5; each with two large
      differences (at different sites)]. Field notes illuminated large differences.
      CONCLUSIONS: Climate scores from staff surveys are not unduly affected by survey
      response rates, but increasing use risks social desirability bias. Safety climate
      provides a partial indicator of performance, but qualitative data are needed to
      understand discrepant results. Safety climate (surveys) and, to a lesser degree,
      teamwork culture (observations) are better indicators of performance than
      organisational climate (surveys) or attempts to evaluate organisational culture
      from time-limited observations. Scoring unobtrusive, time-limited observations to
      evaluate teamwork culture is feasible, but the instrument developed for this
      study needs further testing. A refined observation-based measure would be useful
      to augment or replace surveys. FUNDING: The National Institute for Health
      Research Health Technology Assessment programme.

PMID- 22587943
TI  - High-index faceted noble metal nanocrystals.
AB  - The formation of novel and complex structures with specific morphologies from
      nanocrystals via a direct assembly of atoms or ions remains challenging. In
      recent years, researchers have focused their attention on nanocrystals of noble
      metals and their controlled synthesis, characterization, and potential
      applications. Although the synthesis of various noble metal nanocrystals with
      different morphologies has been reported, most studies are limited to low-index
      facet-terminated nanocrystals. High-index facets, denoted by a set of Miller
      indices {hkl} with at least one index greater than unity, possess a high density
      of low-coordinated atoms, steps, edges, and kinks within these structures and
      serve as more active catalytic sites. With the potential for enhanced catalytic
      performance, researchers have used the insights from shape-controlled nanocrystal
      synthesis to construct noble metal nanocrystals bounded with high-index facets.
      Since the report of Pt tetrahexahedral nanocrystals, researchers have achieved
      significant progress and have prepared nanocrystals with various high-index
      facets. Because of the general order of surface energy for noble metals, high
      index facets typically vanish faster in a crystal growth stage and are difficult
      to preserve on the surface of the final nanocrystals. Therefore researchers have
      had limited opportunities to examine high-indexed noble metal nanocrystals with a
      controlled morphology and investigate their resultant behaviors in depth.  In
      this Account, we thoroughly discuss the basic concepts and state-of-the-art
      morphology control of some noble metal nanocrystals enclosed with high-index
      facets. We briefly introduce high-index facets from both crystallographic and
      geometrical points of view, both of which serve as methods to classify these high
      index facets. Then, we summarize various typical noble metal nanocrystals
      terminated by different types of high-index facets, including {hk0} (h > k > 0),
      {hhl} (h > l > 0), {hkk} (h > k > 0), and {hkl} (h > k > l > 0). In each type, we
      describe several distinct morphologies including convex, concave, and other
      irregular shapes in detail. Based on these remarks, we discuss key factors that
      may induce the variations of Miller indices in each class, such as organic
      capping ligands and metallic cationic species. In a look at applications, we
      review several typical high-indexed noble metal nanocrystals showing enhanced
      electrocatalytic or chemical catalytic activities.

PMID- 22587944
TI  - Interactions of the potent D-amino acid oxidase inhibitor CBIO with morphine in
      pain and tolerance to analgesia.
AB  - A series of experiments using technologies of gene mutation and silencing as well
      as chemical biology have demonstrated that spinal D-amino acid oxidase (DAAO)
      contributes to the development of central sensitization-mediated chronic pain and
      might be a potential molecular target for the treatment of chronic pain. DAAO
      inhibitors are now under clinical investigations for the management of chronic
      neuropathic pain. This study examined the interactions between morphine and the
      DAAO inhibitor CBIO (5-chloro-benzo[d]isoxazol-3-ol) in pain and analgesia
      tolerance mainly in the formalin test. Given subcutaneously CBIO acutely
      interacted with morphine in analgesia in an additive manner both in the acute
      nociception settings (the formalin acute phase nociception, hot-plate test and
      tail immersion test) and in formalin-induced tonic pain. Bi-daily exposure of
      CBIO given subcutaneously for 7 days did not produce self-tolerance to analgesia
      or cross-tolerance to morphine whereas 7-day subcutaneous morphine induced self
      tolerance to analgesia but not cross-tolerance to CBIO. More importantly,
      subcutaneous co-administrations or even single dose of CBIO completely prevented
      or reversed morphine tolerance to analgesia (exhibited by a single dose or a dose
      response curve of morphine) in both formalin-induced acute phase nociception and
      tonic phase pain. These results, for the first time, identified DAAO as an
      efficacious molecule mediating morphine tolerance, in addition to clarifying the
      complex interactions between morphine and DAAO inhibitors probed by CBIO, and
      provided a pharmacological basis for DAAO inhibitors in combination with morphine
      to clinically manage pain.

PMID- 22587945
TI  - Debunking myths of protocol registration.
AB  - Developing and registering protocols may seem like an added burden to systematic
      review investigators. This paper discusses benefits of protocol registration and
      debunks common misperceptions on the barriers of protocol registration. Protocol
      registration is easy to do, reduces duplication of effort and benefits the review
      team by preventing later confusion.

PMID- 22587946
TI  - Establishing a new journal for systematic review products.
AB  - Welcome to a new age in publishing systematic reviews. We hope the launch of
      Systematic Reviews will resonate with a broad spectrum of readers interested in
      using them in a variety of ways, such as providing comprehensive and up to date
      evidence for patient management, informing health policy, and developing rigorous
      practice guidelines. Systematic reviews are increasingly popular. Our journal is
      committed to publishing a wide variety of well conducted and transparently
      reported systematic reviews and associated research. We are open access and
      electronic and not confined by space and so offer scope for publishing reviews in
      detail and providing a modern and innovative approach to publishing. We look
      forward to participating in the voyage with all of our readers.

PMID- 22587948
TI  - Interactions between Fusarium verticillioides, Ustilago maydis, and Zea mays: an
      endophyte, a pathogen, and their shared plant host.
AB  - Highly diverse communities of microbial symbionts occupy eukaryotic organisms,
      including plants. While many well-studied symbionts may be characterized as
      either parasites or as mutualists, the prevalent but cryptic endophytic fungi are
      less easily qualified because they do not cause observable symptoms of their
      presence within their host. Here, we investigate the interactions of an
      endophytic fungus, Fusarium verticillioides with a pathogen, Ustilago maydis, as
      they occur within maize (Zea mays). We used experimental inoculations to evaluate
      metabolic mechanisms by which these three organisms might interact. We assessed
      the impacts of fungal-fungal interactions on endophyte and pathogen growth within
      the plant, and on plant growth. We find that F. verticillioides modulates the
      growth of U. maydis and thus decreases the pathogen's aggressiveness toward the
      plant. With co-inoculation of the endophyte with the pathogen, plant growth is
      similar to that which would be gained without the pathogen present. However, the
      endophyte may also break down plant compounds that limit U. maydis growth, and
      obtains a growth benefit from the presence of the pathogen. Thus, an endophyte
      such as F. verticillioides may function as both a defensive mutualist and a
      parasite, and express nutritional modes that depend on ecological context.

PMID- 22587949
TI  - A novel method for fast and statistically verified morphological characterization
      of filamentous fungi.
AB  - Along with productivity and physiology, morphological growth behavior is the key
      parameter in bioprocess design for filamentous fungi. Despite complex
      interactions between fungal morphology, broth viscosity, mixing kinetics,
      transport characteristics and process productivity, morphology is still commonly
      tackled only by empirical trial-and-error techniques during strain selection and
      process development procedures. In fact, morphological growth characteristics are
      investigated by computational analysis of only a limited number of pre-selected
      microscopic images or via manual evaluation of images, which causes biased
      results and does not allow any automation or high-throughput quantification. To
      overcome the lack of tools for fast, reliable and quantitative morphological
      analysis, this work introduces a method enabling statistically verified
      quantification of fungal morphology in accordance with Quality by Design
      principles. The novel, high-throughput method presented here interlinks fully
      automated recording of microscopic images with a newly developed evaluation
      approach reducing the need for manual intervention to a minimum. Validity of
      results is ensured by concomitantly testing the acquired sample for
      representativeness by statistical inference via bootstrap analysis. The novel
      approach for statistical verification can be equally applied as control logic to
      automatically proceed with morphological analysis of a consecutive sample once
      user defined acceptance criteria are met. Hence, analysis time can be reduced to
      an absolute minimum. The quantitative potential of the developed methodology is
      demonstrated by characterizing the morphological growth behavior of two
      industrial Penicillium chrysogenum production strains in batch cultivation.

PMID- 22587947
TI  - Metagenomics - a guide from sampling to data analysis.
AB  - Metagenomics applies a suite of genomic technologies and bioinformatics tools to
      directly access the genetic content of entire communities of organisms. The field
      of metagenomics has been responsible for substantial advances in microbial
      ecology, evolution, and diversity over the past 5 to 10 years, and many research
      laboratories are actively engaged in it now. With the growing numbers of
      activities also comes a plethora of methodological knowledge and expertise that
      should guide future developments in the field. This review summarizes the current
      opinions in metagenomics, and provides practical guidance and advice on sample
      processing, sequencing technology, assembly, binning, annotation, experimental
      design, statistical analysis, data storage, and data sharing. As more metagenomic
      datasets are generated, the availability of standardized procedures and shared
      data storage and analysis becomes increasingly important to ensure that output of
      individual projects can be assessed and compared.

PMID- 22587950
TI  - The MAP kinase Bbslt2 controls growth, conidiation, cell wall integrity, and
      virulence in the insect pathogenic fungus Beauveria bassiana.
AB  - Entomopathogenic fungi, such as Beauveria bassiana, are key environmental
      pathogens of insects that have been exploited for biological control of insect
      pests. Mitogen-activated protein (MAP) kinases play crucial roles in regulating
      fungal development, growth, and pathogenicity, mediating responses to the
      environment. Bbslt2, encoding for an Slt2 family MAPK, was isolated and
      characterized from B. bassiana. Gene disruption of Bbslt2 affected growth, caused
      a significant reduction in conidial production and viability, and increased
      sensitivity to Congo Red and fungal cell wall degrading enzymes. DeltaBbslt2
      mutants were altered in cell wall structure and composition, which included
      temperature dependent chitin accumulation, reductions in conidial and hyphal
      hydrophobicity, and alterations in cell surface carbohydrate epitopes. The
      DeltaBbslt2 strain also showed hypersensitivity to heat shock and altered
      trehalose accumulation, which could only be partially attributed to changes in
      the expression of trehalase (ntl1). Insect bioassays revealed decreased virulence
      in the DeltaBbslt2 strain using both topical and intrahemoceol injection assays.
      These results indicate that Bbslt2 plays an important role in conidiation,
      viability, cell wall integrity and virulence in B. bassiana. Our findings are
      discussed within the context of the two previous MAP kinases characterized from
      B. bassiana.

PMID- 22587951
TI  - Human renal cancer stem cells.
AB  - Cancer stem cells (CSCs), isolated in renal carcinomas, exhibit tumor-initiating
      capabilities and pluripotency. No specific CSC markers have been identified so
      far; therefore, their characterization is mainly based on functional studies. As
      they are resistant to chemo and radio therapy, renal CSCs may have a relevant
      role in tumor establishment, progression, and recurrence. CSCs were also shown to
      contribute to intra-tumor vasculogenesis through an endothelial differentiation
      and to favor the generation of the pre-metastatic niche through the release of
      exosomes/microvesicles. 

PMID- 22587952
TI  - Assessing biological and chemical signatures related to nutrient removal by
      floating islands in stormwater mesocosms.
AB  - Aquatic floating plants on BioHaven mats were tested for their potential use as a
      Best Management Practice to be incorporated within existing stormwater detention
      ponds. Plants were analyzed for their capability to remove nutrient-pollution in
      parallel with the study of ecological dynamics. Experiments were carried out in
      cylindrical mesocosms of 5 m diameter and 1.2 m height, above-ground pools with a
      water volume of 14 m(3). The design parameters tested were for 5% and 10%
      vegetated floating island coverage of the mesocosm, both with and without
      shoreline plants called littoral zone. This littoral shelf was 0.5 m thick,
      graded at a downward slope of 1:5 toward the center using loamy soil with low
      organic matter content, excavated from below turf grass. Endemic plant species
      were chosen for the experimental location in central Florida based on a wetland
      identification manual by the Florida Department of Environmental Protection to
      ensure the study was not compromised by unique climate requirements of the
      plants. Nutrient and aquatic chemical conditions such as pH, dissolved oxygen,
      temperature, turbidity, and chlorophyll a were monitored to understand their
      relationships to the general wetland ecosystem. Real-time polymerase chain
      reaction analysis identified the microbial activity near the rhizospheric zone.
      Logistical placement considerations were made using spatial sampling across the
      horizontal plane of the mesocosms, beneath and around the root zone, to determine
      if nutrients tend to aggregate around the floating island. This study concluded
      that the application of floating islands as a stormwater technology can remove
      nutrients through plant uptake and biological activity. The most cost-effective
      size in the outdoor mesocosms was 5% surface area coverage of the mat.

PMID- 22587953
TI  - Solubility of organic acids in various methanol and salt concentrations: the
      implication on organic acid sorption in a cosolvent system.
AB  - The well-known cosolvency-induced sorption model is not applicable to predict the
      sorption of carboxylic acids in cosolvent system. To investigate the phenomenon,
      sorption and solubility of chlorinated phenols (2,4-dichlorophenol (2,4-DCP) and
      2,4,6-trichlorophenol (2,4,6-TCP)) and carboxylic acids (benzoic acid and 2,4
      dichlorophenoxyacetic acid (2,4-D)) were measured in soil-methanol mixture with
      various ionic strengths. The sorption (K(m)) of chlorinated phenols was explained
      by a cosolvency-induced sorption model; the inverse log-linear relationship
      between the K(m) and methanol volume fraction (f(c)). However, the K(m) of
      carboxylic acids increased with increasing f(c). This discrepancy was attributed
      to the effect of the carboxylic moiety. To explain the effect, solubility was
      measured for benzoic acid and 2,4,6-TCP from various liquid conditions. For both
      solutes, the cosolvency power (sigma) increased with CaCl(2) concentrations and
      the salting constant (K(s)) became smaller as f(c) increased. However, the sigma
      value at a given salt concentration and the K(s) value at a given f(c) were
      greater for 2,4,6-TCP than for benzoic acid, both of which were due to the
      greater hydrophobicity of the former. Overall, the solubility profiles of the
      both solutes on combination of f(c) and CaCl(2) concentration evidenced no
      specific role of the carboxylic moiety. Therefore, it can be reasonably concluded
      that the positive relationship between K(m) and f(c) for carboxylic organic acid
      can be attributed to the modification of the activity coefficient occurred in the
      solid phase, which cannot be traceable by cosolvency-based model.

PMID- 22587954
TI  - Hand hygiene practices in healthcare: measure and improve.

PMID- 22587955
TI  - Possible contamination of organ preservation fluid with Bacillus cereus: the
      United Kingdom response.
AB  - We describe here the United Kingdom (UK) response following the recent
      international recall of an organ preservation fluid owing to potential Bacillus
      cereus contamination. This fluid is used for the transport of solid organs and
      pancreatic islet cells for transplant. We detail the response mechanisms,
      including the initial risk stratification, investigatory approaches, isolate
      analysis and communications to professional bodies. This report further lays out
      the potential need for enhanced surveillance in UK transplant patients.

PMID- 22587956
TI  - First estimates of influenza vaccine effectiveness among severe influenza cases,
      France, 2011/12.
AB  - Following a suspected virus-vaccine mismatch, the screening method was used to
      estimate in almost real time the influenza vaccine effectiveness (VE) against
      severe cases in high-risk individuals. Data on vaccination status were provided
      by the influenza severe surveillance system and data on vaccination coverage by
      the National Social Security Scheme. The analysis showed a decline of the vaccine
      effectiveness in 2011/12 (VE: 30% (95% CI: 22-39)) compared to 2010/11 (VE: 53%
      (95% CI: 40-67)).

PMID- 22587957
TI  - Four multifaceted countrywide campaigns to promote hand hygiene in Belgian
      hospitals between 2005 and 2011: impact on compliance to hand hygiene.
AB  - Four consecutive one-month campaigns were organised to promote hand hygiene in
      Belgian hospitals between 2005 and 2011. The campaigns included a combination of
      reminders in wards, educational sessions for healthcare workers, promotion of
      alcohol-based hand rub use, increasing patient awareness, and audits with
      performance feedback. Prior and after each one month intervention period, the
      infection control teams measured hand hygiene compliance of healthcare workers by
      direct observation using a standardised observation roster. A total of 738,367
      opportunities for hand hygiene were observed over the four campaigns. Compliance
      with hand hygiene significantly increased from 49.6% before to 68.6% after the
      intervention period for the first, from 53.2% to 69.5% for the second, from 58.0%
      to 69.1% for the third, and from 62.3% to 72.9% for the fourth campaign. The
      highest compliance rates were consistently observed in paediatric units.
      Compliance rates were always markedly lower among physicians than nurses. After
      patient contact and body fluid exposure risk, compliance rates were noticeably
      higher than before patient contact and performing aseptic procedures. We conclude
      that repeated countrywide campaigns to promote hand hygiene result in positive
      long-term outcomes. However, lower compliance rates among physicians compared
      with nurses, before patient contact, and before performing aseptic procedures
      remain challenges for future campaigns.

PMID- 22587958
TI  - Influenza-related deaths--available methods for estimating numbers and detecting
      patterns for seasonal and pandemic influenza in Europe.
AB  - Two methodologies are used for describing and estimating influenza-related
      mortality: Individual-based methods, which use death certification and laboratory
      diagnosis and predominately determine patterns and risk factors for mortality,
      and population-based methods, which use statistical and modelling techniques to
      estimate numbers of premature deaths. The total numbers of deaths generated from
      the two methods cannot be compared. The former are prone to underestimation,
      especially when identifying influenza-related deaths in older people. The latter
      are cruder and have to allow for confounding factors, notably other seasonal
      infections and climate effects. There is no routine system estimating overall
      European influenza-related premature mortality, apart from a pilot system
      EuroMOMO. It is not possible at present to estimate the overall influenza
      mortality due to the 2009 influenza pandemic in Europe, and the totals based on
      individual deaths are a minimum estimate. However, the pattern of mortality
      differed considerably between the 2009 pandemic in Europe and the interpandemic
      period 1970 to 2008, with pandemic deaths in 2009 occurring in younger and
      healthier persons. Common methods should be agreed to estimate influenza-related
      mortality at national level in Europe, and individual surveillance should be
      instituted for influenza-related deaths in key groups such as pregnant women and
      children.

PMID- 22587960
TI  - Evidence summaries: the evolution of a rapid review approach.
AB  - BACKGROUND: Rapid reviews have emerged as a streamlined approach to synthesizing
      evidence - typically for informing emergent decisions faced by decision makers in
      health care settings. Although there is growing use of rapid review 'methods',
      and proliferation of rapid review products, there is a dearth of published
      literature on rapid review methodology. This paper outlines our experience with
      rapidly producing, publishing and disseminating evidence summaries in the context
      of our Knowledge to Action (KTA) research program. METHODS: The KTA research
      program is a two-year project designed to develop and assess the impact of a
      regional knowledge infrastructure that supports evidence-informed decision making
      by regional managers and stakeholders. As part of this program, we have developed
      evidence summaries - our form of rapid review - which have come to be a flagship
      component of this project. Our eight-step approach for producing evidence
      summaries has been developed iteratively, based on evidence (where available),
      experience and knowledge user feedback. The aim of our evidence summary approach
      is to deliver quality evidence that is both timely and user-friendly. RESULTS:
      From November 2009 to March 2011 we have produced 11 evidence summaries on a
      diverse range of questions identified by our knowledge users. Topic areas have
      included questions of clinical effectiveness to questions on health systems
      and/or health services. Knowledge users have reported evidence summaries to be of
      high value in informing their decisions and initiatives. We continue to
      experiment with incorporating more of the established methods of systematic
      reviews, while maintaining our capacity to deliver a final product in a timely
      manner. CONCLUSIONS: The evolution of the KTA rapid review evidence summaries has
      been a positive one. We have developed an approach that appears to be addressing
      a need by knowledge users for timely, user-friendly, and trustworthy evidence and
      have transparently reported these methods here for the wider rapid review and
      scientific community.

PMID- 22587961
TI  - The temperature challenges on cardiac performance in winter-quiescent and
      migration-stage eels Anguilla anguilla.
AB  - The present study was undertaken to examine cardiac responses to some of the
      temperature challenges that eels encounter in their natural environment. The
      contractile properties of ventricular muscle was studied on electrically paced
      tissue strips after long term acclimation at 0  degrees C, 10  degrees C, or 20 
      degrees C, and following acute +/- 10  degrees C temperature changes. The time
      course of contraction, and thus maximal attainable heart rates, was greatly
      influenced by working temperature, but was independent of acclimation history.
      The absolute force of contraction and power production (i.e. the product of force
      and stimulation frequency) was significantly influenced by acute temperature
      decrease from 20  degrees C to 10  degrees C. The role of adrenaline as a
      modulator of contraction force, power production, rates of contraction and
      relaxation, and minimum time in contraction was assessed. Increased adrenergic
      tonus elicited a positive inotropic, temperature-dependent response, but did not
      influence twitch duration. This suggests that adrenaline acts as an agent in
      maintaining an adequate contractile force following temperature challenges. A
      significant increased relative ventricular mass was observed in 0  degrees C and
      10  degrees C-acclimated eels compared to 20  degrees C-acclimated, which
      suggests that at low temperatures, eels secure cardiac output by heart
      enlargement. Inhibition of specific sarcolemmal Ca(2+) channels by selective drug
      treatment revealed that, depending on temperature, L-type channels is the major
      entry site, but also that reverse-mode Na(+)/Ca(2+)-exchange and store operated
      calcium entry contribute to the pool of activator Ca(2+).

PMID- 22587962
TI  - The importance of PROSPERO to the National Institute for Health Research.
AB  - An important activity of the National Institute for Health Research is to
      commission and support the preparation of systematic reviews. For research
      commissioners, the international prospective register for systematic reviews
      known as PROSPERO provides an important further step in ensuring the quality and
      integrity of research evidence and will help avoid unplanned research
      duplication.

PMID- 22587963
TI  - Synthesis of cycloparaphenylenes and related carbon nanorings: a step toward the
      controlled synthesis of carbon nanotubes.
AB  - Since their discovery in 1991, carbon nanotubes (CNTs) have attracted significant
      attention because of their remarkable mechanical, electronic, and optical
      properties. Structural uniformity of the CNT is critically important because the
      sidewall structures (armchair, zigzag, and chiral) determine many of the
      significant properties of CNTs. Ideally researchers would synthesize CNTs with a
      defined target sidewall structure and diameter, but the current synthetic
      methods, such as arc discharge and chemical vapor deposition, only provide CNTs
      as the mixtures of various structures. Purification of these mixtures does not
      allow researchers to isolate a structurally uniform CNT, which is the bottleneck
      for fundamental studies and advanced applications of these materials. Therefore,
      the selective and predictable synthesis of structurally uniform CNTs would
      represent a critical advance in both nanocarbon science and synthetic chemistry.
      This Account highlights our efforts toward the bottom-up synthesis of
      structurally uniform carbon nanotubes (CNTs). We envisioned a bottom-up synthesis
      of structurally uniform CNTs through a controlled growth process from a short
      carbon nanoring (template) that corresponds to the target structure of CNTs. Our
      simple retrosynthetic analysis led to the identification of cycloparaphenylenes
      (CPPs), acene-inserted CPPs, and cyclacenes as the shortest sidewall segments of
      armchair, chiral, and zigzag CNTs, respectively. With this overall picture in
      mind, we initiated our synthetic studies of aromatic rings/belts as an initial
      step toward structurally uniform CNTs in 2005. This research has led to (i) a
      general strategy for the synthesis of CPPs and related carbon nanorings using
      cyclohexane derivatives as a benzene-convertible L-shaped unit, (ii) a modular,
      size-selective, and scalable synthesis of [n]CPPs (a shortest segment of armchair
      CNTs), (iii) the X-ray crystal structure analysis of CPPs, (iv) the design and
      synthesis of acene-inserted CPPs as the shortest segment of chiral CNTs, and (v)
      the first synthesis of cyclo-1,4-naphthylene, a pi-extended CPP. We believe this
      work will serve as important initial steps toward a controlled synthesis of CNTs.

PMID- 22587964
TI  - Developmental expression of chemokine-like factor 1, a novel member of chemokines
      family, in postnatal rat cerebral cortex.
AB  - Chemokine-like factor 1 (CKLF1) has been implicated to induce the migration of
      neuroblastoma cells and is abundant in fetal brain but scarce in adult brain.
      Given the importance of neural cell migration in brain development, it is
      possible that the chemotaxis of CKLF1 is required during brain development.
      Therefore, it is essential to know the detailed expression profiles of CKLF1
      during brain development first. However, the developmental expression patterns of
      CKLF1 still remain unclear. We aimed to investigate the temporal and spatial
      expressions of CKLF1 during cerebral cortex postnatal development in rats. By
      reverse-transcription PCR/immunoblotting at multiple time points, the
      mRNA/protein expressions of CKLF1 were in abundance at birth, then decreased
      progressively within the next two weeks and almost disappeared in adulthood. By
      immunohistochemistry staining, an obvious expression of CKLF1 was observed in the
      cerebral cortex, hippocampus, olfactory bulb, some specific nuclei and
      commissural fibers. Concluding, the temporal expression pattern of CKLF1 was
      coincident with the postnatal developmental stages and the spatial locations of
      CKLF1 were some destinations of neural cell migration or regions where
      myelination normally occurs during cerebrum postnatal development.

PMID- 22587965
TI  - Salivary enzymes are injected into xylem by the glassy-winged sharpshooter, a
      vector of Xylella fastidiosa.
AB  - A few phytophagous hemipteran species such as the glassy-winged sharpshooter,
      Homalodisca vitripennis, (Germar), subsist entirely on xylem fluid. Although
      poorly understood, aspects of the insect's salivary physiology may facilitate
      both xylem-feeding and transmission of plant pathogens. Xylella fastidiosa is a
      xylem-limited bacterium that causes Pierce's disease of grape and other scorch
      diseases in many important crops. X. fastidiosa colonizes the anterior foregut
      (precibarium and cibarium) of H. vitripennis and other xylem-feeding vectors.
      Bacteria form a dense biofilm anchored in part by an exopolysaccharide (EPS)
      matrix that is reported to have a beta-1,4-glucan backbone. Recently published
      evidence supports the following, salivation-egestion hypothesis for the
      inoculation of X. fastidiosa during vector feeding. The insect secretes saliva
      into the plant and then rapidly takes up a mixture of saliva and plant
      constituents. During turbulent fluid movements in the precibarium, the bacteria
      may become mechanically and enzymatically dislodged; the mixture is then egested
      back out through the stylets into plant cells, possibly including xylem vessels.
      The present study found that proteins extracted from dissected H. vitripennis
      salivary glands contain several enzyme activities capable of hydrolyzing
      glycosidic linkages in polysaccharides such as those found in EPS and plant cell
      walls, based on current information about the structures of those
      polysaccharides. One of these enzymes, a beta-1,4-endoglucanase (EGase) was
      enriched in the salivary gland protein extract by subjecting the extract to a
      few, simple purification steps. The EGase-enriched extract was then used to
      generate a polyclonal antiserum that was used for immunohistochemical imaging of
      enzymes in sharpshooter salivary sheaths in grape. Results showed that enzyme
      containing gelling saliva is injected into xylem vessels during sharpshooter
      feeding, in one case being carried by the transpiration stream away from the
      injection site. Thus, the present study provides support for the salivation
      egestion hypothesis.

PMID- 22587966
TI  - Mycobacterium tuberculosis and Clostridium difficille interactomes: demonstration
      of rapid development of computational system for bacterial interactome
      prediction.
AB  - BACKGROUND: Protein-protein interaction (PPI) networks (interactomes) of most
      organisms, except for some model organisms, are largely unknown. Experimental
      methods including high-throughput techniques are highly resource intensive.
      Therefore, computational discovery of PPIs can accelerate biological discovery by
      presenting "most-promising" pairs of proteins that are likely to interact. For
      many bacteria, genome sequence, and thereby genomic context of proteomes, is
      readily available; additionally, for some of these proteomes, localization and
      functional annotations are also available, but interactomes are not available. We
      present here a method for rapid development of computational system to predict
      interactome of bacterial proteomes. While other studies have presented methods to
      transfer interologs across species, here, we propose transfer of computational
      models to benefit from cross-species annotations, thereby predicting many more
      novel interactions even in the absence of interologs. Mycobacterium tuberculosis
      (Mtb) and Clostridium difficile (CD) have been used to demonstrate the work.
      RESULTS: We developed a random forest classifier over features derived from Gene
      Ontology annotations and genetic context scores provided by STRING database for
      predicting Mtb and CD interactions independently. The Mtb classifier gave a
      precision of 94% and a recall of 23% on a held out test set. The Mtb model was
      then run on all the 8 million protein pairs of the Mtb proteome, resulting in 708
      new interactions (at 94% expected precision) or 1,595 new interactions at 80%
      expected precision. The CD classifier gave a precision of 90% and a recall of 16%
      on a held out test set. The CD model was run on all the 8 million protein pairs
      of the CD proteome, resulting in 143 new interactions (at 90% expected precision)
      or 580 new interactions (at 80% expected precision). We also compared the overlap
      of predictions of our method with STRING database interactions for CD and Mtb and
      also with interactions identified recently by a bacterial 2-hybrid system for
      Mtb. To demonstrate the utility of transfer of computational models, we made use
      of the developed Mtb model and used it to predict CD protein-pairs. The cross
      species model thus developed yielded a precision of 88% at a recall of 8%. To
      demonstrate transfer of features from other organisms in the absence of feature
      based and interaction-based information, we transferred missing feature values
      from Mtb orthologs into the CD data. In transferring this data from orthologs
      (not interologs), we showed that a large number of interactions can be predicted.
      CONCLUSIONS: Rapid discovery of (partial) bacterial interactome can be made by
      using existing set of GO and STRING features associated with the organisms. We
      can make use of cross-species interactome development, when there are not even
      sufficient known interactions to develop a computational prediction system.
      Computational model of well-studied organism(s) can be employed to make the
      initial interactome prediction for the target organism. We have also demonstrated
      successfully, that annotations can be transferred from orthologs in well-studied
      organisms enabling accurate predictions for organisms with no annotations. These
      approaches can serve as building blocks to address the challenges associated with
      feature coverage, missing interactions towards rapid interactome discovery for
      bacterial organisms. AVAILABILITY: The predictions for all Mtb and CD proteins
      are made available at: http://severus.dbmi.pitt.edu/TB and
      http://severus.dbmi.pitt.edu/CD respectively for browsing as well as for
      download.

PMID- 22587968
TI  - Cancer stem cells and the impact of Chinese herbs, isolates and other
      complementary medical botanicals: a review.
AB  - To elucidate the connection between the origin of certain cancers and stem cells,
      cancer stem cells, the stem cell niche and the tumor microenvironment, and to
      examine the ability of traditional Chinese herbal medicines and isolates in
      treating these types of cancers, the existing literature was examined and eight
      studies regarding Chinese herbal medicines and the prevention of cancer
      recurrence were critically analyzed and evaluated. Tumor stem cells may be the
      final target of traditional Chinese medicine. Soy flavones, ginsenoside Rg3,
      parthenolide, berbamine and curcumin are several examples of Chinese herbal
      medicines, which have been shown to be effective in the treatment of cancer, and
      seem to act by targeting cancer stem cells and associated pathways resulting in
      tumorigenesis. The treatment approaches combined with an overall treatment
      protocol for the tumor microenvironment and chronic systemic inflammation are
      likely to provide a more successful outcome than a single tactical approach. As
      shown in numerous studies in the literature, using complementary disciplines with
      orthodox treatments may enhance treatment outcomes.

PMID- 22587969
TI  - Taiji practice in Switzerland: a short report.

PMID- 22587970
TI  - The first acupuncture center in the United States: an interview with Dr. Yao Wu
      Lee, Washington Acupuncture Center. Interview by Arthur Yin Fan.

PMID- 22587971
TI  - The balance principle in scientific research.
AB  - The principles of balance, randomization, control and repetition, which are
      closely related, constitute the four principles of scientific research. The
      balance principle is the kernel of the four principles which runs through the
      other three. However, in scientific research, the balance principle is always
      overlooked. If the balance principle is not well performed, the research
      conclusion is easy to be denied, which may lead to the failure of the whole
      research. Therefore, it is essential to have a good command of the balance
      principle in scientific research. This article stresses the definition and
      function of the balance principle, the strategies and detailed measures to
      improve balance in scientific research, and the analysis of the common mistakes
      involving the use of the balance principle in scientific research.

PMID- 22587967
TI  - Invasive non-typhoidal salmonella disease: an emerging and neglected tropical
      disease in Africa.
AB  - Invasive strains of non-typhoidal salmonellae have emerged as a prominent cause
      of bloodstream infection in African adults and children, with an associated case
      fatality of 20-25%. The clinical presentation of invasive non-typhoidal
      salmonella disease in Africa is diverse: fever, hepatosplenomegaly, and
      respiratory symptoms are common, and features of enterocolitis are often absent.
      The most important risk factors are HIV infection in adults, and malaria, HIV,
      and malnutrition in children. A distinct genotype of Salmonella enterica var
      Typhimurium, ST313, has emerged as a new pathogenic clade in sub-Saharan Africa,
      and might have adapted to cause invasive disease in human beings. Multidrug
      resistant ST313 has caused epidemics in several African countries, and has driven
      the use of expensive antimicrobial drugs in the poorest health services in the
      world. Studies of systemic cellular and humoral immune responses in adults
      infected with HIV have revealed key host immune defects contributing to invasive
      non-typhoidal salmonella disease. This emerging pathogen might therefore have
      adapted to occupy an ecological and immunological niche provided by HIV, malaria,
      and malnutrition in Africa. A good understanding of the epidemiology of this
      neglected disease will open new avenues for development and implementation of
      vaccine and public health strategies to prevent infections and interrupt
      transmission.

PMID- 22587972
TI  - [Analysis of composite traditional Chinese medicine constitution: an
      investigation of 974 volunteers].
AB  - OBJECTIVE: To explore the analysis methods for composite traditional Chinese
      medicine (TCM) constitutions. METHODS: The epidemiological data of TCM
      constitutions were collected from 974 volunteers via a cross-sectional survey.
      The samples were classified into 9 constitution types according to the maximal
      standardized scores of imbalanced constitutions. The correlation matrix of 9
      constitutions was computed. The standardized scores of 9 constitutions of all the
      volunteers were ranked respectively, and the composite status of every two
      constitutions was observed using cross tabulation. The constitution types of all
      the volunteers were transformed into ternary code of 9 digits, and the composite
      status of 3 or more than 3 kinds of constitution types was analyzed. RESULTS:
      According to the maximal standardized scores of imbalanced constitutions, of 974
      volunteers, 227, 148, 218, 102, 31, 81, 44, 97 and 26 volunteers had balanced
      constitution, qi-deficiency constitution, yang-deficiency constitution, yin
      deficiency constitution, phlegm-dampness constitution, heat-dampness
      constitution, blood stasis constitution, qi-stagnation constitution, and
      inherited special constitution, respectively. The standardized scores of balanced
      constitution were negatively correlated with those of imbalanced constitutions,
      while there was a positive correlation between the standardized scores of every
      two imbalanced constitutions. Among the 8 imbalanced constitutions, one kind of
      imbalanced constitutions was usually complicated with another kind of imbalanced
      constitutions. The number of qi-deficiency constitution complicated with yang
      deficiency constitution, qi-deficiency constitution complicated with yin
      deficiency constitution, and yin-deficiency constitution complicated with yang
      deficiency constitution ranked the top three. The constitution types of 974
      volunteers were transformed into a total of 465 ternary codes, showing a total of
      465 kinds of constitution types; the simplex constitution, the approximately
      simplex constitution, and the composite constitution of two or more than two
      types were found in 259, 130, and 585 volunteers, respectively. CONCLUSION: Cross
      tabulation can show the composite status of every two constitutions, while the
      ternary code can show the composite status of three or more than three
      constitutions.

PMID- 22587973
TI  - [Acupuncture treatment programs for post-stroke motor rehabilitation in community
      hospitals: study protocol of a multicenter, randomized, controlled trial].
AB  - BACKGROUND: Stroke is responsible for increasingly high rates of mortality and
      disability worldwide. Approximately two million people suffer from stroke for the
      first time in China each year. The high incidence (50%) of post-stroke disability
      brings a heavy burden to patients and their caregivers. Acupuncture has been
      widely used in the communities for post-stroke rehabilitation in China. The
      objective of this trial is to apply our acupuncture research achievement to
      treatment and evaluation of post-stroke hemiplegic patients in community. METHODS
      AND DESIGN: A multicenter, randomized, controlled trial will be performed in
      Longhua Hospital and a number of community health service centers in Shanghai. A
      total of 124 patients (estimated sample size) with post-stroke hemiplegia will be
      randomly divided into an acupuncture group and a control group. The patients
      undergoing randomization should be stratified according to National Institutes of
      Health Stroke Scale score at baseline. Within the acupuncture group, different
      acupuncture protocols are administered to patients with flaccid paralysis or
      spastic paralysis based on the Ashworth Scale. Patients in the acupuncture group
      will also be treated with comprehensive rehabilitation therapy. The control group
      will be treated with comprehensive rehabilitation therapy only. The primary
      outcome measures are the Simplified Fugl-Meyer Motor Scale, the Modified Barthel
      Index, and the Burden of Stroke Scale. Secondary outcome measures are the
      modified Rankin Scale, the modified Ashworth Scale and the Stroke Scale of
      Traditional Chinese Medicine. Outcome measures will be performed after 4 and 8
      weeks of treatment. The patients will be followed up after 6 months. DISCUSSION:
      The results of this study are expected to demonstrate that our standardized
      acupuncture protocol for treating and evaluating post-stroke hemiplegic patients
      will improve motor function and lessen the burden of post-stroke patients within
      the communities. This will provide the evidence to support successful translation
      of acupuncture therapy for post-stroke hemiplegic patients in community hospital
      use. TRIAL REGISTRATION: This trial was registered in Chinese Clinical Trial
      Registry with the registration number ChiCTR-TRC-11001347.

PMID- 22587974
TI  - [Investigation on traditional Chinese medicine syndrome distribution of 4 618
      hepatitis B virus infection subjects in Qidong of Jiangsu Province, China].
AB  - OBJECTIVE: To study the traditional Chinese medicine (TCM) syndrome distribution
      in patients with hepatitis B virus (HBV) infection in Qidong region of Jiangsu
      Province, China. METHODS: A cross-sectional survey was performed. Subjects from
      Qidong of Jiangsu Province of China were screened among the locally enrolled
      residents by detecting hepatitis B surface antigen (HBsAg) from May 2007 to May
      2011 and were assigned to HBsAg-negative cohort or HBsAg-positive cohort. Then,
      the subjects were diagnosed according to alanine aminotransferase, alpha
      fetoprotein and B ultrasound. The syndrome of the subjects was determined using a
      TCM questionnaire consisting of signs and symptoms. RESULTS: A total of 5 908
      subjects were enrolled in this survey, among whom, 4 718 were diagnosed with
      HbsAg infection (positive result of HbsAg detection) and 1 147 were negative. 143
      subjects were excluded for not receiving the blood examination. The final
      diagnoses of the subjects were non-HBV infection (n=1128), HBV carrier (n=4019),
      chronic hepatitis B (n=225), posthepatitic cirrhosis (n=263) or liver cancer
      (n=111). The TCM syndrome differentiation results showed that there were
      differences in syndrome distribution between HBV-infected and non-HBV-infected
      patients. The main syndromes of the HBV-infected patients were qi deficiency, qi
      stagnation, blood stasis and dampness heat, related to the Zang of liver and
      spleen. The distribution principles of TCM syndrome among patients of HBV
      carrier, chronic hepatitis B and cirrhosis were similar. Moreover, with the
      progression of the patients' condition, the scores of syndromes increased, and
      the number of accompanying syndromes increased as well. The main syndromes of
      patients with liver cancer were blood stasis and excess heat, which was slightly
      different from that of the other HBV-infected patients. CONCLUSION: The TCM
      syndrome distribution in patients of HBV infection in Qidong region of Jiangsu
      Province shows regularity. The disorder is mainly due to qi stagnation and blood
      stasis and is also related to deficiency of healthy qi, especially deficiency of
      spleen qi.

PMID- 22587975
TI  - Can heat and cold be parameterized? Clinical data of a preliminary study.
AB  - OBJECTIVE: The aim of this study was to demonstrate whether it is possible to
      objectively assess the effects of acupuncture by microcirculation-related
      parameters in the given clinical scenario, to evaluate the significance of the
      status of capillary perfusion prior to acupuncture for the treatment of a
      clinical cold pattern, and to evaluate the possible role of microcirculation
      related parameters for the future parameterization of the traditional Chinese
      medicine (TCM) diagnosis. METHODS: This prospective, uncontrolled, unblinded
      preliminary clinical trial included 32 elderly patients after surgical treatment
      for femoral fractures. For acupuncture treatment the patients received
      acupuncture with the "leopard spot technique" on the stomach meridian (Liangqiu,
      S34/ST34). Measurements of microcirculation-related parameters (velocity, blood
      flow, haemoglobin, oxygen saturation) by white light spectroscopy and laser
      Doppler were performed prior to and after acupuncture treatment. RESULTS: Two
      subgroups of patients after femur fracture could be identified: a low- and a high
      perfusion group. Capillary flow velocity and blood flow were significantly
      augmented by acupuncture in the low-perfusion group only. In the high-perfusion
      group, there was no significant change of perfusion after acupuncture. The
      statistical analysis of all patients regardless of their pre-acupuncture
      perfusion status revealed no statistically significant alteration after
      acupuncture. The acupuncture effect may have been masked by the inhomogeneity of
      the overall group. CONCLUSION: Microcirculation-related parameters may be
      valuable to measure acupuncture effects objectively and to characterize the
      vegetative functions prior to acupuncture so as to homogenize the comparison
      groups in clinical trials. In our example, a local cold pattern (low capillary
      perfusion of the leg) could be treated successfully by a point which enhances qi
      and blood flow, whereas in heat pattern (high capillary perfusion) this
      intervention had no such effect. Future studies may be directed to correlate the
      vegetative status as measurable by TCM vegetative parameters with the key
      symptoms of TCM diagnosis.

PMID- 22587976
TI  - In vitro and in vivo evaluation of the inhibitory effect of Limnophila indica
      (Linn.) Druce on shigellosis.
AB  - OBJECTIVE: The research aimed to evaluate the anti-Shigella and antacid
      activities of the methanolic extract of Limnophila indica. METHODS: The whole
      plant of L. indica was extracted using methanol and then subjected to preliminary
      chemical screening. The in vitro antibacterial screening on two Gram-positive and
      two Gram-negative bacteria as well as three Shigella species of which two
      bacteria were antibiotic-resistant were evaluated by disc diffusion method.
      Castor oil-induced diarrhoea on Wistar albino rats was performed by using
      loperamide as a standard control. The in vitro antacid activity was tested by
      artificial stomach model. The neutralization efficiency, capacity, volume and
      hydrogen ions consumed were also evaluated. RESULTS: The preliminary chemical
      screening on methanolic extract of L.indica showed the presence of phenolic
      compounds, flavonoids, alkaloids, fats and oils. It was proved to be a potent
      antibacterial agent against the four bacterial strains. Screening against
      Shigella species revealed that it was a powerful antibacterial agent towards
      antibiotic-resistant Shigella species. In the case of in vivo antidiarrheal
      activity, the plant has shown a dose-dependent activity and the lowest dose at
      100 mg/kg gave a much better result than loperamide (P<0.01). The in vitro
      antacid study showed a mild activity. CONCLUSION: As the plant L. indica has been
      proved to be a competent antibacterial as well as a compelling antidiarrheal
      agent with mild antacid activity, this plant can be very well suggested to be an
      eminent substitute for the various synthetic anti-dysentery and antidiarrheal
      agents available in the market.

PMID- 22587978
TI  - Protective effect of Heliotropium eichwaldi against cisplatin-induced
      nephrotoxicity in mice.
AB  - OBJECTIVE: The aim of the present study was to evaluate the nephroprotective
      effect of methanolic extract of Heliotropium eichwaldii (MHE) in mice with
      cisplatin-induced acute renal damage. METHODS: Nephrotoxicity was induced by a
      single intraperitoneal injection of cisplatin (16mg/kg). Swiss albino mice were
      injected with vehicle, cisplatin, cisplatin plus MHE 200 mg/kg and cisplatin plus
      MHE 400mg/kg, respectively. MHE was administered for 7 d at a dose of 200 and 400
      mg/kg per day orally starting 4 d before cisplatin injection. Animals were
      sacrificed 3d after treatment and blood as well as kidney tissue was isolated and
      analyzed. The various parameters such as blood urea nitrogen (BUN), serum
      creatinine (CRE), malondialdehyde (MDA), and catalase (CAT) and superoxide
      dismutase (SOD) activities were analyzed. RESULTS: MHE treatment significantly
      reduced BUN and serum CRE levels elevated by cisplatin administration (P<0.05).
      Also, it significantly attenuated cisplatin-induced increase in MDA level and
      improved the decreased CAT and SOD activities in renal cortical homogenates
      (P<0.05). Additionally, histopathological examination and scoring showed that MHE
      markedly ameliorated cisplatin-induced renal tubular necrosis. CONCLUSION: MHE
      can be considered a potential candidate for protection of nephrotoxicity induced
      by cisplatin.

PMID- 22587977
TI  - Rapid green synthesis of silver nanoparticles from silver nitrate by a
      homeopathic mother tincture Phytolacca Decandra.
AB  - OBJECTIVE: To examine if a homeopathic mother tincture (Phytolacca Decandra) is
      capable of precipitating silver nanoparticles from silver nitrate (AgNO(3)) and
      to characterize the biosynthesized nanoparticles for evaluating their biological
      activities. METHODS: A total of 100 mg of AgNO(3) was added to 20mL of Milli-Q
      water and stirred vigorously. Then 5mL of the homeopathic mother tincture of
      Phytolacca Decandra (ethanolic root extract of Phytolacca decandra) was added and
      stirred continuously. Reduction took place rapidly at 300K and completed in 10
      min as shown by stable light greenish-yellow color of the solution which gave
      colloid of silver nanoparticles. The colloid solution was then centrifuged at
      5000*g to separate the nanoparticles for further use. The nanoparticles were
      characterized by spectroscopic analysis, particle size analysis and zeta
      potential measurements, and morphology was analyzed by atomic force microscopy.
      The drug-DNA interaction was determined by circular dichroism spectrophotometry
      and melting temperature profiles by using calf thymus DNA as the target. The
      biological activities were determined using a cancer cell line A549 in vitro and
      using bacteria Escherichia coli and fungus Saccharomyces cerevisiae as test
      models. RESULTS: Phytolacca Decandra precipitated silver nanoparticles in ambient
      conditions. The nanoparticles had 91 nm particle size, with polydispersity index
      of 0.119 and zeta potential of -15.6 mV. The silver nanoparticles showed
      anticancer and antibacterial properties, but no clear antifungal properties.
      CONCLUSION: This could be a novel environment-friendly method to biosynthesize
      silver nanoparticles using a cost-effective, nontoxic manner. The homeopathic
      mother tincture may utilize this property of nano-precipitation in curing
      diseases or disease symptoms.

PMID- 22587979
TI  - [Chinese herbal medicine Fuzheng Huayu recipe inhibits liver fibrosis by
      mediating the transforming growth factor-beta1/Smads signaling pathway].
AB  - OBJECTIVE: To investigate the mechanism of Fuzheng Huayu recipe (FZHY), a
      compound traditional Chinese herbal medicine, against liver fibrosis related to
      transforming growth factor-beta1 (TGF-beta1)/Smads signaling transduction.
      METHODS: The research consisted of in vitro and in vivo experiments. In the in
      vivo experiment, 37 male Wistar rats were divided into 3 groups: 5 rats in normal
      group, 18 and 14 rats respectively in model and FZHY groups. Liver fibrosis was
      induced in rats of the model group and the FZHY group by intraperitoneal
      injection of dimethylnitrosamine with a dose of 10MUg/kg body weight for 4 weeks.
      Rats in the FZHY group were administered with FZHY for 4 weeks after liver
      fibrosis was induced. After the treatment of FZHY, hydroxyproline (Hyp) content
      in rat liver tissue was assayed by Jamall's method and protein expressions of TGF
      beta1, TGF-beta1 receptor I (TbetaR-I), Smad2, Smad3 and phosphorylated-Smad2/3
      were analyzed by Western blotting. In the in vitro experiment, hepatic stellate
      cells (HSCs) were isolated from normal rats by in situ pronase/collagenase
      perfusion followed by density gradient centrifugation. On the 4th day of cell
      culture, HSCs were stimulated by 2.5 ng/mL TGF-beta1 for 24 h, then incubated
      with the medium containing 10% FZHY-medicated serum or 10MUmol/L SB-431542 (a
      potent and specific inhibitor of TGF-beta1 receptor I kinase) for 24 h. And the
      HSCs without TGF-beta1 stimulating were used as control group. Protein
      expressions and location of alpha-smooth muscle actin (alpha-SMA) and Smad3 in
      HSCs were assayed by immunofluorescent staining, and the image was analyzed by
      Image-Pro Plus 6.1 System. RESULTS: In the in vivo experiment, liver Hyp content
      in the FZHY group was reduced significantly compared with the model group. FZHY
      also down-regulated the protein expressions of TGF-beta1, TbetaR-I and p-Smad2/3
      in fibrotic liver tissue. In the in vitro experiment, FZHY-medicated serum
      incubated with TGF-beta1-stimulated HSCs significantly down-regulated the protein
      expression of alpha-SMA. It also inhibited Smad3 nuclear translocation in TGF
      beta1-stimulated HSCs. CONCLUSION: The mechanism of FZHY against liver fibrosis
      is related to the regulation of TGF-beta1 signaling transduction pathway by
      inhibition of TGF-beta1 and TbetaR-I expressions and Smads activation in fibrotic
      liver tissue and HSCs.

PMID- 22587980
TI  - [Effects of the effective component group of Chinese herbal medicine Xiaoxuming
      Decoction on brain mitochondria in rats with chronic cerebral ischemia].
AB  - OBJECTIVE: To investigate the effects of the effective component group of
      Xiaoxuming Decoction (XXM), a compound traditional Chinese herbal medicine, on
      cerebral mitochondria in rats with chronic cerebral ischemia. METHODS: Rats were
      subjected to permanent bilateral common carotid artery occlusion to induce
      chronic cerebral ischemia. Then, the rats with chronic cerebral ischemia were
      randomly divided into five groups: model group, extract of Ginkgo biloba group
      and low-, medium- and high-dose effective component group of XXM groups. Another
      11 rats without common carotid artery occlusion were used as a sham control.
      Gradient centrifugation was used to obtain the mitochondria from the rat brain.
      Clark oxygen electrode method was used to determine mitochondrial respiratory
      function. Photometric determination was used to measure mitochondrial swelling.
      Rodamine 123 was used to measure mitochondrial membrane potential. Western
      blotting was used to detect mitochondrial apoptosis. RESULTS: Compared with the
      sham group, the mitochondria dysfunction was caused by chronic cerebral ischemia
      associated with the decrease of oxidative phosphorylation parameters and the
      mitochondrial membrane potential, the increase of the mitochondrial degree, the
      elevation of reactive oxygen species level, the decrease in Bcl-2/Bax ratio, and
      the release of cytochrome c. The effective component group of XXM could reduce
      mitochondrial damage induced by chronic cerebral ischemia by improving the
      indexes mentioned above. CONCLUSION: The effective component group of Xiaoxuming
      Decoction can protect brain mitochondrial homeostasis and improve the function of
      mitochondria in rats with chronic cerebral ischemia, which may be the mechanism
      of its protection against chronic cerebral ischemia.

PMID- 22587981
TI  - [Effects of a compound Chinese herbal medicine Yixin Jiedu formula on
      haemodynamic in rats with heart failure of qi-deficiency and blood stasis
      syndrome].
AB  - OBJECTIVE: To explore the effects of Yixin Jiedu Formula (YXJDF), a compound
      Chinese herbal medicine, on hemodynamic and B-type natriuretic (BNP) in a rat
      model of heart failure with qi deficiency and blood stasis syndrome. Moreover,
      its therapeutic effects in improving the symptoms were also studied. METHODS: The
      model of heart failure was established by ligation of left coronary artery in
      rats. Rats were randomly divided into sham-operated group, model group, YXJDF
      group and positive control (sodium fosinopril tablet) group. On the second day
      after the operation, rats in different groups received different treatments. Rats
      in the YXJDF group were treated with YXJDF (9.33g/kg); rats in the positive
      control group received solution of sodium fosinopril tablet (1.2mg/kg) and rats
      in the model and the control groups were given an equal volume of saline,
      respectively. Drugs were delivered by intragastric administration for 28d.
      Symptoms such as respiratory rate and red-green-blue value of color of the
      plantar skin were also collected. Then hemodynamic indexes were evaluated and the
      levels of plasma BNP were examined by enzyme-linked immunosorbent assay (ELISA)
      in all groups. RESULTS: After 28d, rats in the YXJDF group and the positive
      control group were more active than rats in the model group. Both YXJDF and
      sodium fosinopril tablet significantly improved the purple degree of the plantar
      skin and the respiratory rate. Compared with rats in the sham-operated group,
      systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial
      pressure (MAP) of the model group decreased significantly (P<0.05); rats in the
      YXJDF group and the positive control group showed significant improvement on SBP,
      DBP and MAP (P<0.05). In ventricular hemodynamic, left ventricular systolic
      pressure (LVSP), maximal rate of left ventricular systolic pressure
      (LV+dP/dt(max)) and maximal rate of left ventricular diastolic blood pressure (LV
      dP/dt(max)) of the model group were significantly down-regulated when compared
      with the sham-operated group (P<0.05); YXJDF and sodium fosinopril tablet
      increased the LVSP, LV+dP/dt(max) and LV-dP/dt(max) (P<0.05), and thus improved
      ventricular hemodynamic in rats with heart failure. ELISA results showed that
      plasma BNP level of the model group was higher than that of the sham-operated
      group (P<0.05); YXJDF and sodium fosinopril tablet down-regulated the plasma BNP
      level significantly (P<0.05) compared with the model group. CONCLUSION: YXJDF can
      strengthen left ventricular contractile force, increase LVSP, LV+dP/dt(max) and
      LV-dP/dtmax, SBP and SDP, and MAP, and improve hemodynamic indicators in rats
      with heart failure after myocardial infarction. YXJDF can also relieve the
      symptoms of qi deficiency and blood stasis syndrome.

PMID- 22587982
TI  - [Effects of Chinese herbal medicine Feiyanning Decoction on the ratio of
      CD4+CD25+ regulatory T cells and expression of transcription factor Foxp3 in mice
      bearing Lewis lung carcinoma].
AB  - OBJECTIVE: To study the effects of Feiyanning Decoction, a compound traditional
      Chinese herbal medicine, on the ratio of CD4(+)CD25(+) regulatory T cells and
      expression of transcription factor Foxp3 in mice with Lewis lung cancer. METHODS:
      Thirty-two male wild-type C57BL/6 mice aging from 6 to 8 weeks were inoculated
      with Lewis lung cancer cells to establish the tumor-bearing model of Lewis lung
      carcinoma and were randomly divided into model group, Chinese medicine group,
      chemotherapy group and Chinese medicine combined with chemotherapy group. After
      intervention for 14 d with corresponding drugs, behaviors, physical signs and
      changes of feed consumption of the mice were observed. All mice were sacrificed
      after drug treatment, and tumors and organs were removed to weigh and calculate
      organ indexes (lung index, spleen index and thymus index). The percentages of
      CD4(+)CD25(+) regulatory T cells in the thymus, spleen and tumor were determined
      by flow cytometry. The expression of Foxp3 mRNA in the thymus, spleen and tumor
      tissues was detected by quantitative real-time polymerase chain reaction.
      RESULTS: Compared with those in the model group, the mice in the Chinese medicine
      group showed significant reductions in spleen and thymus indexes and tumor
      weight, and elevation in the body weight without tumor (P<0.05). The numbers of
      CD4(+)CD25(+) regulatory T cells in spleen, thymus and tumor were lower in the
      Chinese medicine group than in the model group (P<0.05). The expression of Foxp3
      mRNA in spleen, thymus and tumor was significantly down-regulated in the Chinese
      medicine group compared with the model group (P<0.05). There were no significant
      differences in CD4(+)CD25(+) regulatory T cell ratio and Foxp3 mRNA expression
      between the Chinese medicine combined with chemotherapy group and the
      chemotherapy group. CONCLUSION: Feiyanning Decoction can enhance the antitumor
      immune response and thus play a role in antitumor therapy by reducing the ratio
      of CD4(+)CD25(+) regulatory T cells and down-regulating the expression of Foxp3
      mRNA.

PMID- 22587983
TI  - [Issues on translation of terms in traditional Chinese medicine clinical
      practice].

PMID- 22587984
TI  - Taxonomic revision of three species of the genus Genarchopsis (Digenea:
      Hemiuroidea: Derogenidae) in Japan by molecular phylogenetic analyses.
AB  - The taxonomic status of three nominal species of Genarchopsis (G. goppo Ozaki,
      1925; G. gigi Yamaguti 1939; and G. fellicola Shimazu, 1995) (Digenea:
      Hemiuroidea: Derogenidae) was investigated by molecular phylogenetic analyses
      using partial sequences of the genomic ITS-1 region and the mitochondrial COI.
      The analyzed samples were divided into four groups: Lake Biwa, West Japan,
      Central Japan and G. fellicola. The Lake Biwa group, a sister taxon to the other
      three groups, was interpreted as G. gigi, so we concluded that G. gigi is valid;
      thus, this species is resurrected taxonomically. The specimens from the type host
      caught near the type locality of G. goppo were included in the West Japan group,
      so this group was regarded as G. goppo sensu stricto. Because the phylogenetic
      position of the Central Japan group could not be confirmed, it was identified
      tentatively as G. goppo, even though this species thus becomes paraphyletic. The
      taxonomic validity of G. fellicola was reconfirmed. The divergence time of G.
      gigi is discussed in relation to the geological history of Lake Biwa and the
      origin of host species.

PMID- 22587985
TI  - Knowledge synthesis and the Canadian Institutes of Health Research.
AB  - The Canadian Institutes of Health Research (CIHR) is Canada's premier health
      research funding agency. We fund nearly 14,000 researchers and trainees in four
      theme areas: biomedical, clinical, health services, and population and public
      health research. Our mandate is 'to excel according to international standards of
      scientific excellence, in the creation of new knowledge and its translation into
      improved health for Canadians, more effective health services and products and a
      strengthened Canadian health care system'. Knowledge synthesis is a key element
      of the knowledge-translation objectives of CIHR, as outlined in our definition of
      knowledge-translation.

PMID- 22587986
TI  - The development, characterization, and application of an OATP1B1 inhibition assay
      in drug discovery.
AB  - The pivotal role of organic anion-transporting polypeptide 1B1 (OATP1B1) in drug
      disposition has become clear over the last decade. Therefore, an OATP1B1
      inhibition assay suitable for use within early drug discovery was developed and
      characterized. IC(50) estimates for 10 literature compounds using pitavastatin
      and estradiol-17beta-glucuronide as substrates were within 2-fold of each other.
      In addition, the IC(50) estimates using pitavastatin uptake agreed well with
      literature values (r(2) = 0.92, average fold error = 1.3). However, when estrone
      3-sulfate was used, OATP1B1 inhibition was underpredicted by as much as 10-fold.
      A comparison of uptake in human hepatocytes and OATP1B1 inhibition showed a
      significant correlation (r(2) = 0.53, P < 0.001) for more than 40 compounds.
      These data suggest that, for discrete chemical series, OATP1B1 inhibition data
      may be used as a surrogate for more costly and time-consuming uptake studies in
      hepatocytes. OATP1B1 inhibition data, determined for over 260 compounds
      representing both internal AstraZeneca and literature chemistry, were also used
      to generate a continuous in silico model. The robustness of the model was
      demonstrated by accurately predicting OATP1B1 inhibition for external test sets
      using 50 AstraZeneca compounds (root mean square error = 0.45) and 12 literature
      drugs (RMSE = 0.32). The most important molecular descriptors for the prediction
      of OATP1B1 inhibition were maximal hydrogen bonding strength followed by cLogP.
      This study has shown that a well validated OATP1B1 inhibition assay in
      conjunction with an in silico approaches has the potential to influence
      significantly the design-make-test cycle and subsequently reduce the propensity
      of OATP1B1 ligands.

PMID- 22587987
TI  - Metabolism of (2S)-pterosin A: identification of the phase I and phase II
      metabolites in rat urine.
AB  - The metabolic profile of the potent hypoglycemic agent, (2S)-pterosin A (1), in
      rat urine via intragastrical oral administration was investigated. In total, 19
      metabolites (M1-M19) were identified. Among these, 16 metabolites were
      characterized by high-performance liquid chromatography solid-phase extraction
      tube transfer-NMR, and seven metabolites were further isolated from the treated
      urine to enable further structural determination. Twelve of these are new
      compounds. The phase I metabolites of 1 were formed via various oxidations at
      positions C-3, C-10, C-12, C-13, or C-1 followed by decarboxylation of C-10 or C
      14, and lactonization at C-12/C-14 or C-14/C-12. The phase II metabolites were
      glucuronide conjugates from the parent compound or phase I metabolites. The major
      metabolites were found to be (2S)-14-O-glucuronylpterosin A (M9), (2S)-2
      hydroxymethylpterosin E (M14), and (+/-)-pterosin B (M19). Quantitative HPLC
      analysis of metabolites, based on similar UV absorption and use of the regression
      equation of 1, indicated that ~71% 1 was excreted as metabolites in rat urine.

PMID- 22587988
TI  - Effect of structural variation on aldehyde oxidase-catalyzed oxidation of
      zoniporide.
AB  - Current studies explored the effect of structural changes on the aldehyde oxidase
      (AO)-mediated metabolism of zoniporide (1). Zoniporide analogs with modifications
      of the acylguanidine moiety, the cyclopropyl group on the pyrazole ring, and the
      quinoline ring were studied for their AO-catalyzed metabolism using the human S9
      fraction. Analysis of the half-lives suggested that subtle changes in the
      structure of 1 influenced its metabolism and that the guanidine and the quinoline
      moieties were prerequisites for AO-catalyzed oxidation to 2-oxozoniporide (M1).
      In contrast, replacement of the cyclopropyl group with other alkyl groups was
      tolerated. The effect of structural variation on AO properties was rationalized
      by docking 1 and its analogs into the human AO homology model. These studies
      indicated the importance of electrostatic, pi-pi stacking and hydrophobic
      interactions of the three motifs with residues in the active site. Differences in
      substrate properties were also rationalized by comparing their half-lives with
      cLogD, electrophilicity parameters [electrostatic potential (ESP) charges and
      energy of lowest unoccupied molecular orbitals (E(LUMO))], and the energies of
      formation of tetrahedral intermediates (J Med Chem 50:4642-4647, 2007). Whereas
      the success of energetics in predicting the AO substrate properties of analogs
      was 87%, the predictive ability of other descriptors was none (cLogD) to 60% (ESP
      charges and E(LUMO)). Overall, the structure-metabolism relationship could be
      rationalized using a combination of both the energy calculations and docking
      studies. This combination method can be incorporated into a strategy for
      mitigating AO liabilities observed in the lead candidate or studying structure
      metabolism relationships of other AO substrates.

PMID- 22587989
TI  - Methods for the evaluation of hospital cooperation activities (Systematic review
      protocol).
AB  - BACKGROUND: Hospital partnerships, mergers and cooperatives are arrangements
      frequently seen as a means of improving health service delivery. Many of the
      assumptions used in planning hospital cooperatives are not stated clearly and are
      often based on limited or poor scientific evidence. METHODS: This is a protocol
      for a systematic review, following the Cochrane EPOC methodology. The review aims
      to document, catalogue and synthesize the existing literature on the reported
      methods for the evaluation of hospital cooperation activities as well as methods
      of hospital cooperation. We will search the Database of Abstracts of Reviews of
      Effectiveness, the Effective Practice and Organisation of Care Register, the
      Cochrane Central Register of Controlled Trials and bibliographic databases
      including PubMed (via NLM), Web of Science, NHS EED, Business Source Premier (via
      EBSCO) and Global Health for publications that report on methods for evaluating
      hospital cooperatives, strategic partnerships, mergers, alliances, networks and
      related activities and methods used for such partnerships. The method proposed by
      the Cochrane EPOC group regarding randomized study designs, controlled clinical
      trials, controlled before and after studies, and interrupted time series will be
      followed. In addition, we will also include cohort, case-control studies, and
      relevant non-comparative publications such as case reports. We will categorize
      and analyze the review findings according to the study design employed, the study
      quality (low versus high quality studies) and the method reported in the primary
      studies. We will present the results of studies in tabular form. DISCUSSION:
      Overall, the systematic review aims to identify, assess and synthesize the
      evidence to underpin hospital cooperation activities as defined in this protocol.
      As a result, the review will provide an evidence base for partnerships, alliances
      or other fields of cooperation in a hospital setting. PROSPERO registration
      number: CRD42011001579.

PMID- 22587990
TI  - New diethylsilylacetylenic linker for parallel solid-phase synthesis of libraries
      of hydroxy acetylenic steroid derivatives with improved metabolic stability.
AB  - Acetylenic tertiary alcohols are well-known to be compounds that are biologically
      more stable than their corresponding secondary alcohols. The linkage of an
      acetylenic compound to a polymer support and further introduction of molecular
      diversity was found to be an interesting way to generate libraries of hydroxy
      acetylenic derivatives and thus potentially improve their biological properties.
      For the first time, we describe the loading of an ethynyl steroid to a
      polystyrene-diethylsilane resin and its uses for the solid-phase synthesis of a
      model library of 21 steroid derivatives. Two levels of molecular diversity were
      introduced by successive addition of amino acids and carboxylic acids, and
      hydroxy acetylenic steroids were then released by an acidic treatment in high
      yield and purity without further purification step. 

PMID- 22587991
TI  - AAV micro-dystrophin gene therapy alleviates stress-induced cardiac death but not
      myocardial fibrosis in >21-m-old mdx mice, an end-stage model of Duchenne
      muscular dystrophy cardiomyopathy.
AB  - Duchenne muscular dystrophy (DMD) is a fatal genetic disease caused by the
      absence of the sarcolemmal protein dystrophin. Dilated cardiomyopathy leading to
      heart failure is a significant source of morbidity and mortality in DMD. We
      recently demonstrated amelioration of DMD heart disease in 16 to 20-m-old
      dystrophin-null mdx mice using adeno-associated virus (AAV) mediated micro
      dystrophin gene therapy. DMD patients show severe heart disease near the end of
      their life expectancy. Similarly, mdx mice exhibit profoundly worsening heart
      disease when they reach beyond 21 months of age. To more rigorously test micro
      dystrophin therapy, we treated mdx mice that were between 21.2 and 22.7-m-old
      (average, 22.1 +/- 0.2 months; N=8). The ?R4-23/?C micro-dystrophin gene was
      packaged in the cardiotropic AAV-9 virus. 5*10(12) viral genome particles/mouse
      were delivered to mdx mice via the tail vein. AAV transduction, myocardial
      fibrosis and heart function were examined 1.7 +/- 0.2 months after gene therapy.
      Efficient micro-dystrophin expression was observed in the myocardium of treated
      mice. Despite the robust dystrophin expression, myocardial fibrosis was not
      mitigated. Most hemodynamic parameters were not improved either. However, ECG
      abnormalities were partially corrected. Importantly, treated mice became more
      resistant to dobutamine-induced cardiac death. In summary, we have revealed for
      the first time the potential benefits and limitations of AAV micro-dystrophin
      therapy in end-stage Duchenne dilated cardiomyopathy. Our findings have important
      implications for the use of AAV gene therapy in dilated cardiomyopathy and heart
      failure.

PMID- 22587992
TI  - PKCbetaII modulation of myocyte contractile performance.
AB  - Significant up-regulation of the protein kinase Cbeta(II) (PKCbeta(II)) develops
      during heart failure and yet divergent functional outcomes are reported in animal
      models. The goal here is to investigate PKCbeta(II) modulation of contractile
      function and gain insights into downstream targets in adult cardiac myocytes.
      Increased PKCbeta(II) protein expression and phosphorylation developed after gene
      transfer into adult myocytes while expression remained undetectable in controls.
      The PKCbeta(II) was distributed in a peri-nuclear pattern and this expression
      resulted in diminished rates and amplitude of shortening and re-lengthening
      compared to controls and myocytes expressing dominant negative PKCbeta(II)
      (PKCbetaDN). Similar decreases were observed in the Ca(2+) transient and the
      Ca(2+) decay rate slowed in response to caffeine in PKCbeta(II)-expressing
      myocytes. Parallel phosphorylation studies indicated PKCbeta(II) targets
      phosphatase activity to reduce phospholamban (PLB) phosphorylation at residue
      Thr17 (pThr17-PLB). The PKCbeta inhibitor, LY379196 (LY) restored pThr17-PLB to
      control levels. In contrast, myofilament protein phosphorylation was enhanced by
      PKCbeta(II) expression, and individually, LY and the phosphatase inhibitor,
      calyculin A each failed to block this response. Further work showed PKCbeta(II)
      increased Ca(2+)-activated, calmodulin-dependent kinase IIdelta (CaMKIIdelta)
      expression and enhanced both CaMKIIdelta and protein kinase D (PKD)
      phosphorylation. Phosphorylation of both signaling targets also was resistant to
      acute inhibition by LY. These later results provide evidence PKCbeta(II)
      modulates contractile function via intermediate downstream pathway(s) in cardiac
      myocytes.

PMID- 22587993
TI  - Non-neuronal cholinergic machinery present in cardiomyocytes offsets hypertrophic
      signals.
AB  - Recent work has provided compelling evidence that increased levels of
      acetylcholine (ACh) can be protective in heart failure, whereas reduced levels of
      ACh secretion can cause heart malfunction. Previous data show that cardiomyocytes
      themselves can actively secrete ACh, raising the question of whether this
      cardiomyocyte derived ACh may contribute to the protective effects of ACh in the
      heart. To address the functionality of this non-neuronal ACh machinery, we used
      cholinesterase inhibitors and a siRNA targeted to AChE (acetylcholinesterase) as
      a way to increase the availability of ACh secreted by cardiac cells. By using
      nitric oxide (NO) formation as a biological sensor for released ACh, we showed
      that cholinesterase inhibition increased NO levels in freshly isolated
      ventricular myocytes and that this effect was prevented by atropine, a muscarinic
      receptor antagonist, and by inhibition of ACh synthesis or vesicular storage.
      Functionally, cholinesterase inhibition prevented the hypertrophic effect as well
      as molecular changes and calcium transient alterations induced by adrenergic
      overstimulation in cardiomyocytes. Moreover, inhibition of ACh storage or
      atropine blunted the anti-hypertrophic action of cholinesterase inhibition.
      Altogether, our results show that cardiomyocytes possess functional cholinergic
      machinery that offsets deleterious effects of hyperadrenergic stimulation. In
      addition, we show that adrenergic stimulation upregulates expression levels of
      cholinergic components. We propose that this cardiomyocyte cholinergic signaling
      could amplify the protective effects of the parasympathetic nervous system in the
      heart and may counteract or partially neutralize hypertrophic adrenergic effects.

PMID- 22587994
TI  - Slow freezing and vitrification differentially modify the gene expression profile
      of human metaphase II oocytes.
AB  - BACKGROUND: Cryopreservation is now considered as an efficient way to store human
      oocytes to preserve fertility. However, little is known about the effects of this
      technology on oocyte gene expression. The aim of this study was to examine the
      effect of the two cryopreservation procedures, slow freezing and vitrification,
      on the gene expression profile of human metaphase II (MII) oocytes. METHODS:
      Unfertilized MII oocytes following ICSI failure were cryopreserved either by slow
      freezing or by the Cryotip method for vitrification. After thawing, total RNA was
      extracted and analyzed using Affymetrix Human Genome U133 Plus 2.0 GeneChip
      arrays. The gene expression profiles and associated biological pathways in slowly
      frozen/thawed and vitrified MII oocytes were determined and compared with those
      of non-cryopreserved MII oocytes used as controls. RESULTS: Both cryopreservation
      procedures negatively affected the gene expression profile of human MII oocytes
      in comparison with controls. However, slowly frozen and vitrified MI oocytes
      displayed specific gene expression signatures. Slow freezing was associated with
      down-regulation of genes involved in chromosomal structure maintenance (KIF2C and
      KIF3A) and cell cycle regulation (CHEK2 and CDKN1B) that may lead to a reduction
      in the oocyte developmental competence. In vitrified oocytes, many genes of the
      ubiquitination pathway were down-regulated, including members of the ubiquitin
      specific peptidase family and subunits of the 26S proteasome. Such inhibition of
      the degradation machinery might stabilize the maternal protein content that is
      necessary for oocyte developmental competence. CONCLUSIONS: The low pregnancy
      rates commonly observed when using human MII oocytes after slow freezing-thawing
      may be explained by the alterations of the oocyte gene expression profile.

PMID- 22587995
TI  - Are children born after infertility treatment at increased risk of
      retinoblastoma?
AB  - BACKGROUND: Retinoblastoma (RB) is the most frequent eye tumour in children, with
      an incidence of 1 in 15-20,000 births. It accounts for 11% of all cancers in the
      first year of life. Except for the hereditary forms, its causes are not well
      known. Studies have recently suggested an increased risk of RB among children
      born after IVF, but the relevant literature is sparse. We assessed the
      association between infertility treatment, subfertility and RB. METHODS: We
      included all children living in France diagnosed with RB between 1 January 2000
      and 31 December 2006 at the Institut Curie, the national reference centre for RB
      diagnosis and treatment. We used multiple logistic regression to compare them
      with a national sample of births in France in 1998 and 2003 (n = 28 170).
      RESULTS: The study included 244 non-familial RB cases. The risk of RB increased
      with maternal age [adjusted odds ratio (adj OR) = 2.07, 95% confidence interval
      (CI) 1.33-3.22 at 35-39 years compared with younger than 25 years and adj OR =
      2.42, 95% CI 1.22-4.81 at 40 years or older], but the associations with IVF (adj
      OR = 1.37, 95% CI 0.64-2.95) and ovarian stimulation or intrauterine insemination
      (adj OR = 1.35, 95% CI 0.77-2.38) were not statistically significant after
      adjustment for maternal age and tobacco use. Among women who had no infertility
      treatment, the risk of RB was significantly increased when time to pregnancy
      exceeded 24 months (adj OR = 2.02, 95% CI 1.17-3.48) compared with time to
      pregnancy <= 24 months. CONCLUSIONS: Our study did not observe a significantly
      increased risk of RB associated with infertility treatment, in particular with
      IVF. But we did find an increased risk for women for whom time to pregnancy
      exceeded 24 months.

PMID- 22587996
TI  - Methylation levels at imprinting control regions are not altered with ovulation
      induction or in vitro fertilization in a birth cohort.
AB  - STUDY QUESTION: Do fertility treatments, including ovulation induction (OI),
      alter epigenetic mechanisms such as DNA methylation at imprinted loci? SUMMARY
      ANSWER: We observed small but statistically significant differences in certain
      imprinting control regions (ICRs) based on the method of conception, however,
      these small changes in methylation did not correlate to the overall
      transcriptional levels of the genes adjacent to the ICRs (such as KCNQ1 and
      SNRPN). WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Assisted reproductive technology
      (ART) has been associated with an increase in the risk of rare childhood
      disorders caused by loss of imprinting (LOI). This study provides novel
      epigenetic analyses on infants conceived by OI and examines how methylation
      levels correlate with gene expression. DESIGN: Data and biospecimens used in this
      study were from 147 participants of the Epigenetic Birth Cohort comprising 1941
      mother-child dyads recruited between June 2007 and June 2009 at the Department of
      Obstetrics, Gynecology and Reproductive Biology at Brigham and Women's Hospital
      (BWH) in Boston, MA, USA. Wilcoxon rank-sum tests were used to examine the
      differences in median percent methylation at each differentially methylated
      region (DMR) between the spontaneous conception control group and the fertility
      treatment groups (OI and IVF). PARTICIPANTS AND SETTING: For each woman who
      reported IVF we selected a woman who conceived spontaneously matched on age (+/-
      2 years). To increase efficiency, we matched the same controls from the
      spontaneously conceived group to participants who reported OI. If an appropriate
      control was not identified that had been previously matched to an IVF
      participant, a new control was selected. The final analytic sample consisted of
      61 spontaneous, 59 IVF and 27 OI conceptions. MAIN RESULTS AND THE ROLE OF
      CHANCE: No functionally relevant differences in methylation levels were observed
      across five (out of six) imprinted DMRs in either the placenta or cord blood of
      infants conceived with OI or IVF compared with infants conceived spontaneously.
      While KCNQ1, SNRPN and H19 DMRs demonstrated small but statistically significant
      differences in methylation based on the method of conception, expression levels
      of the genes related to these control regions only correlated with the
      methylation levels of H19. BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION:
      Limitations of our study include the limited sample size, lack of information on
      OI medication used and culture medium for the IVF procedures and underlying
      reasons for infertility among OI and IVF patients. We did not perform allele
      specific expression analyses and therefore cannot make any inferences about LOI.
      GENERALIZABILITY TO OTHER POPULATIONS: These results are likely to be
      generalizable to non-Hispanic white individuals in populations with similar ART
      and fertility treatments.

PMID- 22587997
TI  - Prospective follow-up of 838 fetuses conceived after ovarian stimulation with
      corifollitropin alfa: comparative and overall neonatal outcome.
AB  - STUDY QUESTION: Is treatment with corifollitropin alfa, a new recombinant
      gonadotrophin with sustained follicle-stimulating activity, safe in terms of
      perinatal complications and birth defects in infants conceived following
      corifollitropin alfa treatment for contolled ovarian stimulation (COS)? SUMMARY
      ANSWER: In terms of neonatal outcome and risk of malformations, treatment with a
      single dose of corifollitropin alfa during COS is as safe as treatment with daily
      recombinant FSH (rFSH). WHAT IS KNOWN AND WHAT THIS PAPER ADDS: This is the first
      pooled analysis of individual safety data in terms of neonatal outcome and major
      and minor congenital malformations collected following intervention trials of
      corifollitropin alfa. DESIGN: Pregnancy and follow-up studies were conducted
      prospectively and data were collected from all Phase II and III trials with
      corifollitropin alfa intervention, including two comparative randomized
      controlled trials (RCTs) in which patients received either a single dose of
      corifollitropin alfa or daily rFSH for the first 7 days of COS. Patients with
      ongoing pregnancies at 10 weeks after embryo transfer were followed up to labour
      and the health of the offspring was assessed up to 4-12 weeks after birth.
      PARTICIPANTS AND SETTING: Following corifollitropin alfa treatment prior to IVF
      or ICSI, the health of 677 pregnant women, 838 fetuses and 806 live born infants
      was evaluated. MAIN RESULTS AND THE ROLE OF CHANCE: Among 440 fetuses in the
      corifollitropin alfa arm and 381 fetuses in the rFSH arm of the two RCTs, there
      were 424 (96.4%) and 370 (98.7%) live births, respectively. Neonatal
      characteristics, the frequency of premature births and the incidence of infant
      adverse events were similar in both treatment arms. The overall incidence of any
      congenital malformations in live born infants was 16.3 and 17.0%, with major
      malformation rates of 4.0 and 5.4% in the corifollitropin alfa and rFSH groups,
      respectively [odds ratio (OR) for major malformations, 0.71; 95% confidence
      interval, 0.36-1.38]. From 838 fetuses assessed in all corifollitropin alfa
      intervention trials, there were 806 (96.2%) live births with a major malformation
      rate of 4.5% in live born infants. BIAS, CONFOUNDING AND OTHER REASONS FOR
      CAUTION: Both RCTs had a double-blind and active-controlled design and the
      adjudication of congenital malformations was also performed in a blinded fashion.
      As the total number of major malformations was limited (37), the confidence
      interval around the OR was rather wide. GENERALISABILITY TO OTHER POPULATIONS:
      The similarity of corifollitropin alfa and rFSH with respect to the incidence of
      congenital malformations was consistent across the RCTs and pregnancy type
      (singleton, multiple). This suggests that this similarity could hold in general.
      Overall incidences, however, may depend on the definitions of malformations and
      rules to adjudicate these events as major or minor.

PMID- 22587998
TI  - Serum and peritoneal interleukin-33 levels are elevated in deeply infiltrating
      endometriosis.
AB  - BACKGROUND: Interleukin 33 (IL-33) is a cytokine involved in fibrotic disorders.
      We have analyzed IL-33 levels in the sera and peritoneal fluids of women with
      various forms of endometriosis and investigated the correlation with disease
      activity. METHODS: We conducted a prospective laboratory study in a tertiary-care
      university hospital between January 2005 and December 2010. Five hundred and ten
      women with histologically proven endometriosis and 132 endometriosis-free
      controls were enrolled in this study. Complete surgical exploration of the
      abdominopelvic cavity was performed in each patient. Blood samples and peritoneal
      fluids were obtained before and during surgical procedures, respectively. IL-33
      was measured by an enzyme-linked immunosorbent assay in sera and peritoneal
      fluids, and the concentrations correlated with the extent and the severity of
      endometriotic lesions. RESULTS: IL-33 was detectable in 23.1% of serum samples
      from all 642 women studied and 75.0% of peritoneal fluid samples studied (44
      women with endometriosis and 36 controls). Serum IL-33 was higher in deeply
      infiltrating endometriosis (DIE) (median, 104.9 pg/ml; range, 8.0-104.9) than in
      endometriosis-free women (median, 61.3 pg/ml; range, 7.5-526.0; P = 0.022) or in
      women affected by superficial endometriosis (median, 36.8 pg/ml; range, 7.5
      179.0; P < 0.001). Peritoneal IL-33 was higher in DIE than in endometriosis-free
      women (median, 642.0 pg/ml; range, 25.9-3350.6 versus median, 194.2 pg/ml; range,
      12.7-1818.2, respectively; P = 0.003). We found positive correlations between
      serum IL-33 concentration and intensity of dysmenorrhea (r = 0.174; P = 0.028)
      and gastrointestinal symptoms (r = 0.199; P = 0.027), total number of DIE lesions
      (r = 0.224; P = 0.016) and the worst DIE lesion (r = 0.299; P < 0.001).
      CONCLUSIONS: In spite of the number of samples with undetectable levels, serum IL
      33 is abnormally elevated in women with endometriosis and principally in DIE.
      Elevated serum IL-33 is correlated with the intensity of preoperative painful
      symptoms, and with the extent and severity of the DIE. IL-33 may be considered as
      a novel cytokine involved in the pathogenesis of DIE.

PMID- 22587999
TI  - The nuclear factor-kappaB pathway is involved in matrix metalloproteinase-9
      expression in RU486-induced endometrium breakdown in mice.
AB  - BACKGROUND: Progesterone-withdrawal (WP)-induced endometrial breakdown occurs in
      both physiological and pathological processes such as menstruation and abortion.
      However, the underlying mechanisms are not clearly understood. As the nuclear
      factor-kappaB (NF-kappaB) pathway has been proposed to play a role in endometrial
      breakdown, we tested this hypothesis using RU486-induced mouse menstruation-like
      model. METHODS: The activation of NF-kappaB was evaluated by
      immunohistochemistry, western blot and immunofluorescence. The expression of
      matrix metalloproteinase-9 (MMP9) was analyzed by real-time PCR and its proteins
      by gelatin zymography and western blot. Chromatin immunoprecipitation was used to
      investigate the direct binding of NF-kappaB to MMP9 gene promoter. Inhibitors of
      NF-kappaB were used to block its signal in vivo and in vitro to analyze the
      function of NF-kappaB in the tissue breakdown process. RESULTS: Administration of
      RU486 resulted in increased phospho-IkappaB levels and nuclear translocation of
      p65 in decidual stromal cells, accompanied by the up-regulation of NF-kappaB
      inducing kinase and IkappaB kinase beta mRNA. The NF-kappaB inhibitor,
      'pyrrolidine dithiocarbamate' partially suppressed the RU486-induced endometrial
      breakdown, thus verifying the role of this pathway in vivo. MMP9 was up- and down
      regulated following the NF-kappaB activation and inhibition, respectively. RU486
      stimulated recruitment of NF-kappaB p65 to the MMP9 promoter and further
      increased its expression. Effects of NF-kappaB activation and inactivation on
      MMP9 expression were further explored in human stromal cells in vitro. A similar
      MMP9 expression pattern was observed in cultured human, as well as mouse,
      decidual stromal cells following RU486 treatment. CONCLUSIONS: The activation of
      the NF-kappaB pathway induces downstream target genes, including MMP9 from
      stromal cells to facilitate tissue breakdown in mouse uterus, highlighting the
      likelihood that this regulatory pattern exists in the human endometrium.

PMID- 22588000
TI  - Somatostatin and somatostatin analogues reduce PDGF-induced endometrial cell
      proliferation and motility.
AB  - BACKGROUND: Endometriosis is characterized by ectopic implantation of endometrial
      cells, which show increased proliferation and migration. Somatostatin (SST) and
      its analogues inhibit normal and cancer cell growth and motility through the SST
      receptors, sst1-5. Cortistatin (CST), which displays high structural and
      functional homology with SST, binds all ssts, as well as MrgX2. Our objective was
      to investigate the gene expression of the SST/CST system and to determine the
      effect of SST and its analogues on platelet-derived growth factor (PDGF)-induced
      proliferation and motility in telomerase-immortalized human endometrial stromal
      cell (T HESC) line and in primary endometrial stromal cell (ESCs) isolated from
      human endometriotic tissues. METHODS: Ectopic endometrial tissues were collected
      from women (n= 23) undergoing laparoscopic surgery for endometriosis (Stage
      III/IV). Gene expression was evaluated by real-time PCR, cell motility by wound
      healing assay, protein expression and beta-actin rearrangement by
      immunofluorescence, cell proliferation by the Alamar blue assay and ERK1/2 and
      Akt phosphorylation by western blot. RESULTS: Human endometriotic tissues,
      primary ESCs and T HESCs expressed SST, CST and ssts. SST, its analogues SOM230
      and octreotide, as well as CST, counteracted PDGF-induced proliferation and
      migration in both ESCs and T HESCs. SST also inhibited vascular endothelial
      growth factor and metalloprotease-2 mRNA expression, and reduced basal and PDGF
      induced ERK1/2 phosphorylation. CONCLUSION: These results indicate that the
      SST/CST system is expressed in endometriotic tissues and cells. The inhibitory
      effects of SST and its analogues on PDGF-induced proliferation and motility
      suggest that these peptides may represent promising tools in the treatment of
      endometriosis.

PMID- 22588001
TI  - The selective vitamin D receptor agonist, elocalcitol, reduces endometriosis
      development in a mouse model by inhibiting peritoneal inflammation.
AB  - BACKGROUND: Endometriosis, which is characterized by the growth of endometrial
      tissue at ectopic locations as well as vascular development and inflammation, is
      still an unmet clinical need since an optimal drug that allows for both pain and
      infertility management does not exist. Since both the eutopic and the ectopic
      endometrium express the vitamin D receptor (VDR), and VDR agonists are endowed
      with anti-proliferative and anti-inflammatory properties, we evaluated the effect
      of elocalcitol, a VDR agonist with low calcaemic liability, in a mouse model of
      experimentally induced endometriosis. METHODS AND RESULTS: Endometriosis was
      induced by injection of syngeneic endometrial tissue fragments into adult Balb/c
      female mice. After having confirmed by immunohistochemistry that endometriotic
      lesions developing in mice expressed VDR, the mice were administered with
      elocalcitol (100 MUg/kg) or vehicle orally, once a day, for various durations of
      time. In this model, elocalcitol was able to reduce total lesion weight up to 70%
      upon treatment for 1 week before and 2 weeks after disease induction.
      Interestingly, a therapeutic effect was also observed on already established
      lesions. Elocalcitol was shown to reduce the capacity of mouse endometrial cells
      to adhere to collagen. In addition in treated mice, a decreased state of
      peritoneal inflammation was demonstrated by the inhibition of macrophage
      recruitment and inflammatory cytokine secretion. CONCLUSIONS: The VDR agonist
      elocalcitol inhibits lesion development in a validated mouse model of
      endometriosis, and exerts a protective effect on both the implantation and
      organization of transferred endometrial tissue. These preliminary data in mice
      provide a sound rationale for further testing in primate models and eventually in
      humans.

PMID- 22588002
TI  - Cajal's first steps in scientific research.
AB  - More than 125 years ago, Santiago Ramon y Cajal was able to draft and prove the
      neuron doctrine, and later, to develop prophetic theories about neural function
      and plasticity, many of which have been proven by current neuroscience. It was
      chance that made Cajal, during his doctorate studies, have his first contact with
      histology and force him to study the then current theories about pathogenesis of
      inflammation. Thus, he gained knowledge of the vascular hypothesis, by Julius
      Cohnheim, a German pathologist who, opposing the opinion of his teacher and
      father of cellular pathology, Rudolf Virchow, made leukocytes the protagonists of
      inflammation, given their ability to develop ameboid movements directed by
      chemical signals. Cohnheim's chemotactic theory deeply influenced Cajal's
      conception of biology. So, the basic postulates of chemotaxis can be identified
      at different moments in Cajal's research, from the description of the "growth
      cone" in embryonic neuroblasts, the origin of the neurotrophic theory, to the
      proposal of the pathophysiological mechanisms of neuronal plasticity. From
      Cajal's point of view, the neurons move during their development and also adapt
      to different external circumstances. Chemical endogenous substances can stimulate
      this movement in a similar way to leukocytes during the process of inflammation.

PMID- 22588003
TI  - Mode-dependent effect of high-frequency electrical stimulation of the anterior
      thalamic nucleus on amygdala-kindled seizures in rats.
AB  - Deep brain stimulation (DBS) is an emerging treatment of epilepsy. Anterior
      nucleus of the thalamus (ANT) is considered to be an attractive target due to its
      close connection to the limbic structures and wide regions of neocortex. The
      present study aimed to investigate the effects of high frequency stimulation
      (HFS) targeting the ANT on amygdala-kindled seizures in Wistar rats in two
      different stimulation modes i.e. pre-treatment and post-treatment stimulations,
      mimicking the scheduled and responsive stimulations in clinical use respectively.
      When fully-kindled seizures were achieved by daily amygdala kindling (1 s train
      of 1 ms pulses at 60 Hz), HFS (15 min train of 100 MUs pulses at 150 Hz and 450
      800 MUA) was applied in two modes for 10 days. Bilateral post-treatment with HFS
      reduced the incidence of generalized seizures and the mean behavioral seizure
      stage and shortened average afterdischarge duration (ADD) and generalized seizure
      duration (GSD), while bilateral pre-treatment with HFS resulted in a similar but
      much weaker inhibition of seizures. On the other hand, we also found the two
      stimulation modes both increased the afterdischarge threshold (ADT) and the
      differences of current intensity between ADT and generalized seizure threshold
      (GST) i.e. Delta(GST-ADT). However, Delta(GST-ADT) increased by at least 20 MUA
      in bilateral post-treatment group, while less in bilateral pre-treatment group.
      Additionally, unilateral post-treatment with HFS failed to inhibit seizures. Our
      data show that anti-epileptic effect of bilateral post-treatment with HFS of ANT
      is much stronger than that of bilateral pre-treatment HFS, indicating bilateral
      responsive stimulation might be more appropriate for clinical anti-epileptic
      treatment of ANT HFS.

PMID- 22588004
TI  - Growth comparison of several Escherichia coli strains exposed to various
      concentrations of lactoferrin using linear spline regression.
AB  - BACKGROUND: We wanted to compare growth differences between 13 Escherichia coli
      strains exposed to various concentrations of the growth inhibitor lactoferrin in
      two different types of broth (Syncase and Luria-Bertani (LB)). To carry this out,
      we present a simple statistical procedure that separates microbial growth curves
      that are due to natural random perturbations and growth curves that are more
      likely caused by biological differences.Bacterial growth was determined using
      optical density data (OD) recorded for triplicates at 620 nm for 18 hours for
      each strain. Each resulting growth curve was divided into three equally spaced
      intervals. We propose a procedure using linear spline regression with two knots
      to compute the slopes of each interval in the bacterial growth curves. These
      slopes are subsequently used to estimate a 95% confidence interval based on an
      appropriate statistical distribution. Slopes outside the confidence interval were
      considered as significantly different from slopes within. We also demonstrate the
      use of related, but more advanced methods known collectively as generalized
      additive models (GAMs) to model growth. In addition to impressive curve fitting
      capabilities with corresponding confidence intervals, GAM's allow for the
      computation of derivatives, i.e. growth rate estimation, with respect to each
      time point. RESULTS: The results from our proposed procedure agreed well with the
      observed data. The results indicated that there were substantial growth
      differences between the E. coli strains. Most strains exhibited improved growth
      in the nutrient rich LB broth compared to Syncase. The inhibiting effect of
      lactoferrin varied between the different strains. The atypical enteropathogenic
      aEPEC-2 grew, on average, faster in both broths than the other strains tested
      while the enteroinvasive strains, EIEC-6 and EIEC-7 grew slower. The
      enterotoxigenic ETEC-5 strain, exhibited exceptional growth in Syncase broth, but
      slower growth in LB broth. CONCLUSIONS: Our results do not indicate clear growth
      differences between pathogroups or pathogenic versus non-pathogenic E. coli.

PMID- 22588006
TI  - Aryl aryl methyl thio arenes prevent multidrug-resistant malaria in mouse by
      promoting oxidative stress in parasites.
AB  - We have synthesized a new series of aryl aryl methyl thio arenes (AAMTAs) and
      evaluated antimalarial activity in vitro and in vivo against drug-resistant
      malaria. These compounds interact with free heme, inhibit hemozoin formation, and
      prevent Plasmodium falciparum growth in vitro in a concentration-dependent
      manner. These compounds concentration dependently promote oxidative stress in
      Plasmodium falciparum as evident from the generation of intraparasitic oxidants,
      protein carbonyls, and lipid peroxidation products. Furthermore, AAMTAs deplete
      intraparasite GSH levels, which is essential for antioxidant defense and survival
      during intraerythrocytic stages. These compounds displayed potent antimalarial
      activity not only in vitro but also in vivo against multidrug-resistant
      Plasmodium yoelii dose dependently in a mouse model. The mixtures of enantiomers
      of AAMTAs containing 3-pyridyl rings were found to be more efficient in providing
      antimalarial activity. Efforts have been made to synthesize achiral AAMTAs 17-23
      and among them, compound 18 showed significant antimalarial activity in vivo.

PMID- 22588005
TI  - Temporal expression of hypoxia-regulated genes is associated with early changes
      in redox status in irradiated lung.
AB  - The development of normal lung tissue toxicity after radiation exposure results
      from multiple changes in cell signaling and communication initiated at the time
      of the ionizing event. The onset of gross pulmonary injury is preceded by tissue
      hypoxia and chronic oxidative stress. We have previously shown that development
      of debilitating lung injury can be mitigated or prevented by administration of
      AEOL10150, a potent catalytic antioxidant, 24h after radiation. This suggests
      that hypoxia-mediated signaling pathways may play a role in late radiation
      injury, but the exact mechanism remains unclear. The purpose of this study was to
      evaluate changes in the temporal expression of hypoxia-associated genes in
      irradiated mouse lung and determine whether AEOL10150 alters expression of these
      genes. A focused oligo array was used to establish a hypoxia-associated gene
      expression signature for lung tissue from sham-irradiated or irradiated mice
      treated with or without AEOL10150. Results were further verified by RT-PCR. Forty
      four genes associated with metabolism, cell growth, apoptosis, inflammation,
      oxidative stress, and extracellular matrix synthesis were upregulated after
      radiation. Elevated expression of 31 of these genes was attenuated in animals
      treated with AEOL10150, suggesting that expression of a number of hypoxia
      associated genes is regulated by early development of oxidative stress after
      radiation. Genes identified herein could provide insight into the role of hypoxic
      signaling in radiation lung injury, suggesting novel therapeutic targets, as well
      as clues to the mechanism by which AEOL10150 confers pulmonary radioprotection.

PMID- 22588007
TI  - Mechanism of superoxide and hydrogen peroxide generation by human electron
      transfer flavoprotein and pathological variants.
AB  - Reactive oxygen species production by mitochondrial enzymes plays a fundamental
      role both in cellular signaling and in the progression of dysfunctional states.
      However, sources of reactive oxygen species and the mechanisms by which enzymes
      produce these reactive species still remain elusive. We characterized the
      generation of reactive oxygen species by purified human electron-transfer
      flavoprotein (ETF), a mitochondrial enzyme that has a central role in the
      metabolism of lipids, amino acids, and choline. The results showed that ETF
      produces significant amounts of both superoxide and hydrogen peroxide in the
      presence of its partner enzyme medium-chain acyl-CoA dehydrogenase (MCAD). ETF
      mediated production of reactive oxygen species is partially inhibited at high
      MCAD/ETF ratios, whereas it is enhanced at high ionic strength. Determination of
      the reduction potentials of ETF showed that thermodynamic properties of the FAD
      cofactor are changed upon formation of a complex between ETF and MCAD, supporting
      the notion that protein:protein interactions modulate the reactivity of the
      protein with dioxygen. Two pathogenic ETF variants were also studied to determine
      which factors modulate the reactivity toward molecular oxygen and promote
      reactive oxygen species production. The results obtained show that destabilized
      conformations and defective protein:protein interactions increase the ability of
      ETF to generate reactive oxygen species. A possible role for these processes in
      mitochondrial dysfunction in metabolic disorders of fatty acid beta-oxidation is
      discussed.

PMID- 22588008
TI  - Why prospective registration of systematic reviews makes sense.
AB  - Prospective registration of systematic reviews promotes transparency, helps
      reduce potential for bias and serves to avoid unintended duplication of reviews.
      Registration offers advantages to many stakeholders in return for modest
      additional effort from the researchers registering their reviews.

PMID- 22588010
TI  - A randomized controlled trial of the efficacy and cost-effectiveness of a brief
      intensified cognitive behavioral therapy and/or pharmacotherapy for mood and
      anxiety disorders: design and methods.
AB  - BACKGROUND: Anxiety and mood disorders involve a high disease burden and are
      associated with high economic costs. A stepped-care approach intervention and
      abbreviated diagnostic method are assumed to increase effectiveness and
      efficiency of the mental healthcare and are expected to reduce economic costs.
      METHODS: Presented are the rationale, design, and methods of a two-armed
      randomized controlled trial comparing 'treatment as usual' (TAU) with a brief
      intensified cognitive behavioral therapy (CBT) and/or pharmacotherapy. Eligible
      participants (N=500) of five Dutch outpatient Mental Healthcare Centers are
      randomly assigned to either TAU or to the experimental condition (brief CBT
      and/or pharmacotherapy). Data on patients' progress and clinical effectiveness of
      treatment are assessed at baseline, post-treatment (3 months after baseline), and
      at 6 and 12 months post-treatment by Routine Outcome Monitoring (ROM). Cost
      analysis is performed on the obtained data. DISCUSSION: Since few studies have
      investigated both the clinical and cost effectiveness of a stepped-care approach
      intervention and a shortened diagnostic ROM method in both anxiety and/or mood
      disorders within secondary mental health care, the results of this study might
      contribute to the improvement of (cost)-effective treatment options and
      diagnostic methods for these disorders.

PMID- 22588009
TI  - Repeat prenatal corticosteroid prior to preterm birth: a systematic review and
      individual participant data meta-analysis for the PRECISE study group (prenatal
      repeat corticosteroid international IPD study group: assessing the effects using
      the best level of evidence) - study protocol.
AB  - BACKGROUND: The aim of this individual participant data (IPD) meta-analysis is to
      assess whether the effects of repeat prenatal corticosteroid treatment given to
      women at risk of preterm birth to benefit their babies are modified in a
      clinically meaningful way by factors related to the women or the trial protocol.
      METHODS/DESIGN: The Prenatal Repeat Corticosteroid International IPD Study Group:
      assessing the effects using the best level of Evidence (PRECISE) Group will
      conduct an IPD meta-analysis. The PRECISE International Collaborative Group was
      formed in 2010 and data collection commenced in 2011. Eleven trials with up to
      5,000 women and 6,000 infants are eligible for the PRECISE IPD meta-analysis. The
      primary study outcomes for the infants will be serious neonatal outcome (defined
      by the PRECISE International IPD Study Group as one of death (foetal, neonatal or
      infant); severe respiratory disease; severe intraventricular haemorrhage (grade 3
      and 4); chronic lung disease; necrotising enterocolitis; serious retinopathy of
      prematurity; and cystic periventricular leukomalacia); use of respiratory support
      (defined as mechanical ventilation or continuous positive airways pressure or
      other respiratory support); and birth weight (Z-scores). For the children, the
      primary study outcomes will be death or any neurological disability (however
      defined by trialists at childhood follow up and may include developmental delay
      or intellectual impairment (developmental quotient or intelligence quotient more
      than one standard deviation below the mean), cerebral palsy (abnormality of tone
      with motor dysfunction), blindness (for example, corrected visual acuity worse
      than 6/60 in the better eye) or deafness (for example, hearing loss requiring
      amplification or worse)). For the women, the primary outcome will be maternal
      sepsis (defined as chorioamnionitis; pyrexia after trial entry requiring the use
      of antibiotics; puerperal sepsis; intrapartum fever requiring the use of
      antibiotics; or postnatal pyrexia). DISCUSSION: Data analyses are expected to
      commence in 2011 with results publicly available in 2012.

PMID- 22588011
TI  - Repair of atrioventricular septal defect associated with tetralogy of Fallot or
      double-outlet right ventricle: 30 years of experience.
AB  - BACKGROUND: The surgical outcomes of atrioventricular septal defect (AVSD)
      associated with tetralogy of Fallot (TOF) or double-outlet right ventricle (DORV)
      have improved in recent times. However, high mortality and reoperation rates are
      still reported. This study reviews our surgical experience in patients with
      complete AVSD and TOF or DORV. METHODS: Between 1980 and 2010, 48 consecutive
      patients with AVSD associated with TOF (n = 26) or DORV (n = 22) underwent
      complete repair; of which, 19 had staged repair. A transatrial-transpulmonary
      approach with the 2-patch technique was the preferred surgical technique. Data
      were obtained from inpatient and outpatient medical files. RESULTS: The mortality
      rates were 8.3% (4 of 48) for in-hospital death and 13.6% (6 of 44) for late
      death. Mean follow-up was 8.0 +/- 8.7 years (median 10.8 years; range from 2
      months to 30 years). Actuarial survival was 76% at 5 years and 71% at 20 years.
      No deaths occurred after 2001. Reoperations were required in 16 of 48 patients
      (33%). The overall freedom from reoperation was 55% at 5 and 20 years. Down
      syndrome was protective for reoperation (p = 0.022). CONCLUSIONS: Complete AVSD
      associated with TOF or DORV can be repaired with good survival. Detachment of the
      superior bridging leaflet provided excellent exposure. However, reoperation rate
      remains high.

PMID- 22588012
TI  - Dynamic assessment of mitral annular force profile in an ovine model.
AB  - BACKGROUND: Limited knowledge exists regarding the forces that act on devices
      implanted in the mitral annulus. Determining the peak magnitudes, directions,
      rates, variation throughout the cardiac cycle, and change with left ventricular
      pressure (LVP) will aid in device development and evaluation. METHODS: Novel
      transducers with the ability to measure forces in the septal-lateral and
      transverse directions were implanted in six healthy ovine subjects. Forces were
      measured for cardiac cycles reaching a peak LVP of 90, 125, 150, 175, and 200 mm
      Hg. RESULTS: The septal-lateral force was observed to significantly increase from
      3.9 +/- 0.8 N (90) to 5.2 +/- 1.0 N (125) p < 0.001, 5.9 +/- 0.9 N (150) p <
      0.001, 6.4 +/- 1.2 N (175) p < 0.001, and 6.7 +/- 1.5 N (200 mm Hg) p < 0.001.
      Similarly, the transverse force was seen to increase from 2.6 +/- 0.6 N (90) to
      3.8 +/- 1.0 N (125) p < 0.01, 4.6 +/- 1.3 N (150) p < 0.001, 4.3 +/- 1.2 N (175)
      p < 0.001, and 3.5 +/- 0.7 N (200 mm Hg) p < 0.05. In comparison, the septal
      lateral force was significantly greater than the transverse force at 90 (p <
      0.05), 125 (p < 0.05), 175 (p < 0.001), and 200 mm Hg (p < 0.0005). CONCLUSIONS:
      Annular forces and their variations with LVP through the cardiac cycle are
      described. The results demonstrate differences in force magnitude and rate for
      increasing levels of LVP between the septal-lateral and transverse directions.
      These directional differences have strong implications in the development of
      future mitral devices.

PMID- 22588013
TI  - Cognitive deficits in animal models of basal ganglia disorders.
AB  - The two most common neurological disorders of the basal ganglia are Parkinson's
      disease (PD) and Huntington's disease (HD). The most overt symptoms of these
      diseases are motoric, reflecting the loss of the striatal medium spiny neurons in
      HD and ascending substantia nigra dopaminergic cells in PD. However, both disease
      processes induce insidious psychiatric and cognitive syndromes that can manifest
      well in advance of the onset of motor deficits. These early deficits provide an
      opportunity for prophylactic therapeutic intervention in order to retard disease
      progression from the earliest possible point. In order to exploit this
      opportunity, animal models of HD and PD are being probed for the specific
      cognitive deficits represented in the disease states. At the neuronal level,
      these deficits are typically, but not exclusively, mediated by disruption of
      parallel corticostriatal loops that integrate motor information with sensory and
      higher order, "executive" cognitive functions. Dysfunction in these systems can
      be probed with sensitive behavioural tests that selectively probe these cognitive
      functions in mouse models with focal lesions of striatal or cortical regions, or
      of specific neurotransmitter systems. Typically these tests were designed and
      validated in rats. With the advent of genetically modified mouse models of
      disease, validated tests provide an opportunity to screen mouse models of disease
      for early onset cognitive deficits. This review seeks to draw together the
      literature on cognitive deficits in HD and PD, to determine the extent to which
      these deficits are represented in the current animal models of disease, and to
      evaluate the viability of selecting cognitive deficits as potential therapeutic
      targets. This article is part of a Special Issue entitled 'Animal Models'.

PMID- 22588014
TI  - The effect of 5-fluorouracil on the long term survival and proliferation of cells
      in the rat hippocampus.
AB  - Chemotherapy has been reported to produce cognitive impairments in a significant
      number of cancer patients. These deficits frequently involve aspects of spatial
      or declarative memory which can persist for up to several years after completion
      of the treatment. We have recently shown that 5-fluorouracil (5-FU), a commonly
      used chemotherapy drug, induces cognitive impairment and a reduction in
      hippocampal neurogenesis using a rat model of chemotherapy (Elbeltagy et al.
      [17]). The present study examines the effects of two weeks of 5-FU treatment on
      cell proliferation in the sub granular zone (SGZ) of the dentate gyrus and the
      survival of newly dividing cells over a six week period after the end of
      treatment. Cell proliferation at each time point was quantified by staining for
      the cell proliferation marker Ki67 while the survival of cells, dividing at the
      start of treatment, was determined by quantification of BrdU positive cell
      numbers after pulse labelling with BrdU at the start of drug treatment. The
      results show that 2 weeks of 5-FU treatment did not significantly reduce cell
      proliferation in the SGZ immediately after treatment. However cell proliferation
      was significantly reduced, compared to saline treated controls, two weeks after
      the end of treatment and remained significantly reduced at 6 weeks. The survival
      of cells, dividing at the start of treatment, was significantly reduced when
      quantified immediately after the end of treatment and continued to decline
      compared with control animals over the following 2 weeks but no further change
      occurred at 6 weeks. Quantification of COX-2 positive cell numbers in the
      hippocampus did not correlate with the reduction in cell proliferation or
      survival suggesting that inflammation is not responsible for these changes. These
      results demonstrate that 5-FU has delayed and prolonged effects on hippocampal
      neurogenesis after the end of chemotherapy treatment. This correlates with
      patient reports of continued cognitive impairment after treatment and indicates
      that changes in neurogenesis may underlie these effects.

PMID- 22588015
TI  - Predicting infectious complications in neutropenic children and young people with
      cancer (IPD protocol).
AB  - BACKGROUND: A common and potentially life-threatening complication of the
      treatment of childhood cancer is infection, which frequently presents as fever
      with neutropenia. The standard management of such episodes is the extensive use
      of intravenous antibiotics, and though it produces excellent survival rates of
      over 95%, it greatly inconveniences the three-fourths of patients who do not
      require such aggressive treatment. There have been a number of studies which have
      aimed to develop risk prediction models to stratify treatment. Individual
      participant data (IPD) meta-analysis in therapeutic studies has been developed to
      improve the precision and reliability of answers to questions of treatment effect
      and recently have been suggested to be used to answer questions regarding
      prognosis and diagnosis to gain greater power from the frequently small
      individual studies. DESIGN: In the IPD protocol, we will collect and synthesise
      IPD from multiple studies and examine the outcomes of episodes of febrile
      neutropenia as a consequence of their treatment for malignant disease. We will
      develop and evaluate a risk stratification model using hierarchical regression
      models to stratify patients by their risk of experiencing adverse outcomes during
      an episode. We will also explore specific practical and methodological issues
      regarding adaptation of established techniques of IPD meta-analysis of
      interventions for use in synthesising evidence derived from IPD from multiple
      studies for use in predictive modelling contexts. DISCUSSION: Our aim in using
      this model is to define a group of individuals at low risk for febrile
      neutropenia who might be treated with reduced intensity or duration of antibiotic
      therapy and so reduce the inconvenience and cost of these episodes, as well as to
      define a group of patients at very high risk of complications who could be
      subject to more intensive therapies. The project will also help develop methods
      of IPD predictive modelling for use in future studies of risk prediction.

PMID- 22588016
TI  - Male participation in prevention programmes of mother to child transmission of
      HIV: a protocol for a systematic review to identify barriers, facilitators and
      reported interventions.
AB  - BACKGROUND: Infection with the HIV and AIDS are leading causes of morbidity and
      mortality among women and children worldwide. Prevention of mother-to-child
      transmission of HIV (PMTCT) programs were developed to protect women and their
      babies from having HIV infection. However, knowledge on how male participation
      has been applied to these programs is limited. We present a research protocol for
      a review which seeks to determine the effects of male participation on female
      uptake of PMTCT programs, and assess how this male participation has been
      investigated and documented worldwide. METHODS: This is a systematic review of
      published literature. We will attempt to identify all studies relevant to the
      subject written in the English language from January 1998 to June 2011.
      Electronic searches of the PubMED, EMBASE, CINAHL, and LILACS databases will be
      conducted using the relevant medical subject headings. Reference lists of
      identified studies and previous reviews will be manually checked for articles of
      interest. We shall also contact authors on the field for any relevant material.
      Two authors (FM and LM) will independently screen potential articles for
      eligibility using well-defined inclusion and exclusion criteria. They will
      independently assess the methodological quality of each included paper using the
      Jadad scale for randomized controlled trials, and the Newcastle-Ottawa scale for
      observational studies. Then they will independently extract data from the studies
      using a pre-established data extraction form. The primary outcome data will be
      female uptake of PMTCT services following a male/couple intervention, while
      secondary outcome measures will include indicators and barriers of male
      participation in PMTCT activities among others. During the data extraction
      process, discrepancies between the two authors will be sorted out by discussion
      or consultation with a third party (LT). The analysis and reporting of the review
      will be according to the PRISMA and MOOSE guidelines. Any identified clinical or
      statistical heterogeneity will be explored. Where possible, a random-effects meta
      analysis will be performed to obtain aggregate estimates. We will also assess
      publication bias using funnel plots. Analysis of other outcomes will be
      descriptive.

PMID- 22588017
TI  - Reclassification and subtyping of so-called malignant fibrous histiocytoma of
      bone: comparison with cytogenetic features.
AB  - BACKGROUND: The diagnostic entity malignant fibrous histiocytoma (MFH) of bone
      is, like its soft tissue counterpart, likely to be a misnomer, encompassing a
      variety of poorly differentiated sarcomas. When reviewing a series of 57 so
      called MFH of bone within the framework of the EuroBoNeT consortium according to
      up-to-date criteria and ancillary immunohistochemistry, a fourth of all tumors
      were reclassified and subtyped. METHODS: In the present study, the cytogenetic
      data on 11 of these tumors (three myoepithelioma-like sarcomas, two
      leiomyosarcomas, one undifferentiated pleomorphic sarcoma with incomplete
      myogenic differentiation, two undifferentiated pleomorphic sarcomas, one
      osteosarcoma, one spindle cell sarcoma, and one unclassifiable biphasic sarcoma)
      are presented. RESULTS: All tumors were high-grade lesions and showed very
      complex karyotypes. Neither the overall pattern (ploidy level, degree of
      complexity) nor specific cytogenetic features distinguished any of the subtypes.
      The subgroup of myoepithelioma-like sarcomas was further investigated with regard
      to the status of the EWSR1 and FUS loci; however, no rearrangement was found. Nor
      was any particular aberration that could differentiate any of the subtypes from
      osteosarcomas detected. CONCLUSIONS: chromosome banding analysis is unlikely to
      reveal potential genotype-phenotype correlations between morphologic subtypes
      among so-called MFH of bone.

PMID- 22588018
TI  - Using nitrile functional groups to replace amines for solution-deposited single
      walled carbon nanotube network films.
AB  - Amine-terminated self-assembled monolayers (SAMs) can be utilized to selectively
      adsorb semiconducting single-walled carbon nanotubes (S-SWNTs), but are not
      ideal. Formation of these monolayer films from silanes can be dramatically
      influenced by atmospheric and other processing conditions, resulting in poor
      quality SAMs or irreproducible results. The surface sorting method of fabricating
      these semiconducting nanotube networks (SWNTnts) can become ineffective if the
      functionalized surface is not smooth with high amine density. However, by
      replacing the amine with a nitrile group, SAM formation can be made more
      controllable and reproducible. Upon SWNT deposition, the nitrile group was found
      to not only adsorb higher density SWNTnts but also sort the nanotubes
      efficiently, as shown by micro-Raman spectroscopy. Upon testing these SWNTnts for
      device performance, these thin-film transistors (TFTs) were also found to yield
      higher quality devices than those fabricated on amine surfaces. Overall, these
      results expand the applicability of surface sorting and SWNT adsorption to other
      organic functionalities for nanotube separation. This report provides an outline
      of the merits and characterization of using the nitrile functional group for the
      separation and adsorption of SWNTs and its integration in network TFTs.

PMID- 22588019
TI  - A molecular network underlying spontaneous cAMP oscillation and synchronization
      in Dictyostelium.
AB  - We propose a molecular network, incorporating both adaptation and
      phosphorylation, to account for the spontaneous cAMP oscillation of Dictyostelium
      discoideum. We have modified the scheme previously proposed by Loomis and his
      collaborators so as to include adaptation by the cAMP receptor and such that
      extracellular cAMP is formed by the secreted intracellular cAMP instead of being
      directly produced by adenylyl cyclase. Furthermore, our scheme provides better
      robustness, and can be applied to spontaneous cAMP production by a cluster of
      cells.

PMID- 22588020
TI  - False mathematical reasoning in biology.
AB  - Some consequences of fallacious mathematical reasoning in the recent literature
      of mathematical biology are highlighted.

PMID- 22588021
TI  - Extinction conditions for Y-linked mutant-alleles through two-sex branching
      processes with blind-mating structure.
AB  - A new two-sex bidimensional branching process is introduced to model the
      evolution of the number of carriers of an allele and its mutations of a Y-linked
      gene. A population is assumed in which females and males coexist and mate without
      the gene influencing the mating process. It is deduced from the model that the
      key determining conditions for the extinction or survival of the allele are given
      by the probability that an offspring is female, the rate of mutation, and the
      mean number of offspring per mating unit. It is also proved that the destiny of
      the allele's mutations in the population also depends on the survival or
      extinction of the original allele.

PMID- 22588022
TI  - Modelling the effect of phosphorylation on the circadian clock of Drosophila.
AB  - It is by now well known that, at the molecular level, the core of the circadian
      clock of most living species is a negative feedback loop where some proteins
      inhibit their own transcription. However, it has recently been shown that post
      translational processes, such as phosphorylations, are essential for a correct
      timing of the clock. Depending on which sites of a circadian protein are
      phosphorylated, different properties such as degradation, nuclear localization
      and repressing power can be altered. Furthermore, phosphorylation domains can be
      related in a positive way, giving rise to consecutive phosphorylations, or in a
      negative way, hindering phosphorylation at other domains. Here we present a
      simple mathematical model of a circadian protein having two mutually exclusive
      domains of phosphorylation. We show that the system has limit cycles that arise
      from a unique fixed point through a Hopf bifurcation. We find a set of
      parameters, with realistic values, for which the limit cycle has the same period
      as the wild type circadian oscillations of the fruit fly. The domains act as a
      switch, in the sense that alterations in their phosphorylation can alter the
      period of circadian oscillation in opposite ways, increasing or decreasing the
      period of the wild type oscillations. In particular, we show that our model is
      able to reproduce some of the experimental results found for switch-like
      phosphorylations of the PER protein of the circadian clock of the fly Drosophila
      melanogaster.

PMID- 22588023
TI  - A mathematical model of ParA filament-mediated chromosome movement in Caulobacter
      crescentus.
AB  - Caulobacter crescentus uses the dynamic interactions between ParA and ParB
      proteins to segregate copies of its circular chromosome. In this paper, we
      develop two mathematical models of the movement of the circular chromosome of
      this bacterium during division. In the first model, posed as a set of stochastic
      differential equations (SDE), we propose that a simple biased diffusion mechanism
      for ParB/ParA interactions can reproduce the observed patterns of ParB and ParA
      localization in the cell. The second model, posed as a set of nonlinear partial
      differential equations, is a continuous treatment of the problem where we use
      results from the SDE model to describe ParB/ParA interactions and we also track
      ParA monomer dynamics in the cytoplasm. For both models, we show that if ParB
      complexes bind weakly and nonspecifically to ParA filaments, then they can
      closely track and move with the edge of a shrinking ParA filament bundle.
      Unidirectional chromosome movement occurs when ParB complexes have a passive role
      in depolymerizing ParA filaments. Finally, we show that tight control of ParA
      filament dynamics is essential for proper segregation.

PMID- 22588024
TI  - Do the chaotic features of gait change in Parkinson's disease?
AB  - Some previous studies have focused on chaotic properties of Parkinson's disease
      (PD). It seems that considering PD from dynamical systems perspective is a
      relevant method that may lead to better understanding of the disease. There is
      some ambiguity about chaotic nature in PD symptoms and normal behaviour. Some
      studies claim that normal gait has somehow a chaotic behaviour and disturbed gait
      in PD has decreased chaotic nature. However, it is worth noting that the basis of
      this idea is the difference of fractal behaviour in gait of normal and PD
      patients, which is concluded from Long Range Correlation (LRC) indices. Our
      primary calculations show that a large number of normal persons and patients have
      similar LRC. It seems that chaotic studies on PD need a different view. Because
      of short time recording of symptoms, accurate calculation of chaotic features is
      tough. On the other hand, long time recording of symptoms is experimentally
      difficult. In this research, we have first designed a physiologically plausible
      model for normal and PD gait. Then, after validating the model with neural
      network classifier, we used the model for extracting long time simulation of
      stride in normal and PD persons. These long time simulations were then used for
      calculating the chaotic features of gait. According to change of phase space
      behaviour and alteration of three largest lyapunov exponents, it was observed
      that simulated normal persons act as chaotic systems in stride production, but
      simulated PD does not have chaotic dynamics and is stochastic. Based on our
      results, it may be claimed that normal gait has chaotic nature which is disturbed
      in PD state. Surely, long time real recordings from gait signal in normal persons
      and PD patients are necessary to warranty this hypothesis.

PMID- 22588025
TI  - Prevalence of hyponatremia on geriatric wards compared to other settings over
      four decades: a systematic review.
AB  - Aim of the study was to analyze temporal trends in prevalence of hyponatremia
      over four decades in different settings. A systematic review of the literature
      from 1966 to 2009 yielded prevalences of hyponatremia, with standard errors (SE)
      and pooled estimated means (PEM), calculated by year and setting (geriatric, ICU,
      other hospital wards, psychiatric hospitals, nursing homes, outpatients). 53
      studies were included. Prevalence of hyponatremia was stable from 1976 to 2006,
      and higher on geriatric wards accept for ICU: e.g. PEM prevalence of mild
      hyponatremia (serum sodium <135 mM) was 22.2% (95%CI 20.2-24.3) on geriatric
      wards, 6.0% (95%CI 5.9-6.1) on other hospital wards and 17.2% (SE 7.0) in one ICU
      study; for severe hyponatremia (serum sodium<125 mM) these figures were 4.5%
      (95%CI 3.0-6.1), 0.8% (95%CI 0.7-0.8) and 10.3% (SE 5.6). In nursing homes PEM
      prevalence of mild hyponatremia was 18.8% (95%CI 15.6-22.2). The higher
      prevalence on geriatric wards could partly be explained by age-related changes in
      the regulation of serum sodium. Other underlying factors can be the presence of
      multiple diagnoses and the use of polypharmacy.

PMID- 22588026
TI  - First BAFF gene cloned from an aquatic mammal.
AB  - The finless porpoise (Neophocaena phocaenoides) is one of the smallest cetacean
      species. Research into the immune system of the finless porpoise is essential to
      the protection of this species, but, to date, no genes coding for proteins from
      the tumor necrosis factor family (TNF family) have yet been reported from finless
      porpoises. The TNF B cell activating factor (BAFF) is critical to B cell
      survival, proliferation, maturation, and immunoglobulin secretion and to T cell
      activation. It acts through its three receptors, BAFF-R, BCMA, and TACI. In the
      present study, the full-length cDNA of BAFF (designated NpBAFF) from the finless
      porpoise was cloned using RT-PCR and rapid amplification of cDNA ends (RACE)
      techniques, and its biological activities have been characterized. To our
      knowledge, this is the first report of any BAFF gene being cloned from an aquatic
      mammal. The full-length cDNA of NpBAFF consists of 1502 bases including an 852 bp
      open reading frame encoding 283 amino acids. This protein was found to contain a
      predicted transmembrane domain, a putative furin protease cleavage site, and a
      typical TNF homology domain corresponding to other, known BAFF homologues.
      Sequence comparison indicated that the amino acid sequence of NpBAFF was very
      similar to its bovine (87.68%), porcine (76.33%), hircine (87.68%) and canine
      (82.19%) counterparts. The predicted three-dimensional (3D) structure of the
      NpsBAFF monomer, analyzed by comparative protein modeling, revealed that it was
      very similar to its human counterpart. Phylogenetic analysis indicated that
      NpBAFF showed a notable homology with Artiodactyla BAFFs. The SUMO-NpsBAFF was
      efficiently expressed in Escherichia coli BL21 (DE3) and confirmed by SDS-PAGE
      and Western blot analysis. Laser scanning confocal microscopy analysis showed
      that NpsBAFF could bind to its receptors on B cells. In vitro, MTT assays
      indicated that SUMO-NpsBAFF could promote the survival or proliferation of mouse
      splenic B cells grown with anti-mouse IgM. These findings indicate that NpBAFF
      plays an important role in the survival or proliferation of B cells and has
      functional cross-reactivity among cetaceans and other mammals. The present
      findings may provide valuable information for research into the immune system of
      the finless porpoise.

PMID- 22588027
TI  - Analyses of chromosome copy number and expression level of four genes in the
      ciliate Chilodonella uncinata reveal a complex pattern that suggests epigenetic
      regulation.
AB  - Chilodonella uncinata, like all ciliates, contains two distinct nuclei in every
      cell: a germline micronucleus and a somatic macronucleus. The macronucleus
      develops from the zygotic nucleus through a series of chromosomal rearrangements.
      Macronuclear development in C. uncinata yields a nucleus with highly amplified
      gene-sized chromosomes. The macronucleus is transcriptionally active during
      vegetative growth while there is no expression in the micronucleus except during
      a brief period following conjugation. Gene family evolution in ciliates occurs
      through complex processes including gene duplication and an alternative
      processing of scrambled genes. Here we use quantitative PCR to compare relative
      expression levels of eight genes (SSU-rDNA, actin, alpha-tubulin and five beta
      tubulin sequences) to their abundance as macronuclear chromosomes. We show that
      three strains of the morphospecies C. uncinata share similar patterns across all
      loci. For example, we find an inverse correlation among five beta-tubulin genes
      whereby the more abundant macronuclear chromosomes have lower levels of
      expression compared to less abundant chromosomes. We discuss the implication of
      our findings, which suggest that epigenetic mechanisms maintain chromosome copy
      number in C. uncinata.

PMID- 22588028
TI  - Gender and sexual behavior modulate the composition of serum lipocalins in Nile
      tilapia (Oreochromis niloticus).
AB  - In tilapia species, plasma lipoproteins with high electrophoretic mobility
      function in intra- and intergender communication. Blood samples taken at onset
      and peak of daily sexual activity from dominant and subordinate Oreochromis
      niloticus males and females were fractionated by native gel electrophoresis and
      the fast-migrating proteins were subjected to mass spectrometry. Mining the
      sequence data of the Cichlid Genome Consortium, we identified 11 proteins from
      the lipocalin super-family and characterized their genes' structures.
      Phylogenetic and structural analyses subdivided these genes into two classes: (I)
      3-coding-exon apolipoproteins and (II) more complex 6-coding-exon sulfide-bond
      containing lipocalins. Five apolipoproteins and PTGDSL1, TBTBP, and MSP proteins
      were modulated by gender and sexual behavior. PTGDSL1 protein was only observed
      in the plasma serum of dominant males. However, the cysteine residue in the
      position that is crucial for synthetase activity in mammalian prostaglandin D
      synthetases was not conserved in PTGDSL1 or PTGDSL2 proteins. In line with
      previous reports suggesting their involvement in male functions as pheromone
      transporters, TBTBP and MSP proteins were not detected in females at the onset of
      daily activity. Their increasing amount in males was concordant with the increase
      in apolipoproteins AFP4L, APOA4a, APOA4b, APO14kD and APOC2, which were detected
      exclusively in dominant males, indicating a possible role in mobilization of the
      energy required to maintain their social hierarchy.

PMID- 22588029
TI  - Aortic valve replacement with the Cardioprotese Premium bovine pericardium
      bioprosthesis: four-year clinical results.
AB  - OBJECTIVES: This study reports the initial clinical and echocardiographic results
      of the Premium bioprosthetic aortic valve up to 4 years of follow-up. METHODS:
      Between October 2007 and July 2011, 121 consecutive patients were submitted for
      aortic valve replacement with the Premium bioprosthetic valve. The mean age was
      68 +/- 9 years and 64 patients were males. The patients were periodically
      evaluated by clinical and echocardiographic examinations. The mean follow-up was
      21 months (min = 2, max = 48), yielding 217 patients/year for the analysis.
      RESULTS: The hospital mortality was 8%. Late survival at 3 years was 89% (95% CI:
      81.9-93.3%), and 80% of the patients were in NYHA functional class I/II. The
      rates of valve-related complications were low, with a linearized incidence of
      0.9%/100 patients/year for thromboembolic complications, 0% for haemorrhagic
      events and 0.9%/100 patients/year of bacterial endocarditis. There was no case of
      primary structural valve dysfunction. The mean effective orifice area was 1.61 +/
      0.45 cm(2); mean gradient 13 +/- 5 mmHg and peak gradient 22 +/- 9 mmHg.
      Significant patient-prosthesis mismatch was found in only 11% of the cases.
      CONCLUSIONS: The Premium bioprosthetic aortic valve demonstrated very
      satisfactory clinical and echocardiographic results up to 4 years, similar to
      other commercially available, third-generation bioprosthetic valves.

PMID- 22588030
TI  - Chest wall giant lipoma with a thirty-year history.
AB  - Benign chest wall tumours are very uncommon and chest wall lipomas are rarely
      reported in literature. We report herein a case of a 68-year old man who
      developed a giant, symptomless mass of the chest wall. A chest computed
      tomography scan evidenced a solid neoplasm measuring 27 cm in its major axis. A
      radical excision was performed and the histology was consistent with lipoma. To
      our knowledge, this is the first case reporting a giant lipoma of the chest wall
      with a thirty-year history.

PMID- 22588031
TI  - Usefulness of chest images for the assessment of pectus excavatum before and
      after a Nuss repair in adults.
AB  - OBJECTIVES: The aim of this study was to evaluate whether chest radiographs could
      offer useful information for the assessment of pectus excavatum (PE) before and
      after Nuss repair in adults. METHODS: A total of 154 adults, with a mean age of
      24.0 +/- 5.0 years (range, 18-44 years), who underwent a Nuss repair of PE, with
      a mean follow-up of 42 months (range, 14-71 months), were included in this
      retrospective study. Sixty-two of these patients were also evaluated after the
      pectus bar removal, with a mean follow-up of 13 months (range, 6-44 months). The
      preoperative and postoperative imaging modalities were compared. RESULTS: The
      preoperative mean Haller indices measured on computed tomography (CT) and chest
      radiographs were 4.61 +/- 1.58 (range, 2.6-11.9) and 3.82 +/- 1.17 (range, 2.0
      10.2), respectively. The Pearson correlation coefficient between the two
      parameters was 0.757. The postoperative mean Haller index measured on chest
      radiographs was 2.86 +/- 0.56 (range, 1.7-5.4) and showed statistically
      significant improvement compared with the preoperative index (P < 0.001). The
      mean sternovertebral (SV) distances detected on preoperative and postoperative
      (>6 months after surgery) lateral chest radiographs were 7.67 +/- 1.89 cm (range,
      2.5-12.9 cm) and 9.89 +/- 1.80 cm (range, 4.6-15.0 cm), respectively, showing
      statistically significant improvement (P < 0.001). The mean sternovertebral (SV)
      distance in patients after the bar removal detected on lateral chest radiographs
      was 9.25 +/- 2.14 cm, also showing statistically significant improvement compared
      with the preoperative value (P < 0.001). CONCLUSIONS: Haller indices measured
      using chest radiographs and CT showed a strong correlation. Therefore, chest
      radiographs can be used as an alternative tool for the preoperative evaluation of
      PE. The Nuss operation significantly improved SV distances detected on lateral
      chest radiographs. Lateral chest radiographs can be used as a simple modality for
      the objective quantitative assessment of the anatomic results and follow-up of
      the Nuss operation in adults.

PMID- 22588032
TI  - Is alternative cardiac surgery an option in adults with congenital heart disease
      referred for thoracic organ transplantation?
AB  - OBJECTIVES: We analysed the outcomes of adults with congenital heart disease
      (ACHD) referred for thoracic organ transplantation who underwent non-transplant
      cardiac surgery as an alternative management option. METHODS: Adult patients with
      congenital heart disease assessed for heart or heart-lung transplant were
      identified from the departmental database. A retrospective analysis of the
      medical records, transplant assessment data and surgical notes was carried out.
      RESULTS: One hundred and twenty-six patients were assessed between January 2000
      and July 2011. Non-transplant cardiac surgery was performed in 14 (11%) patients.
      There were nine males with a median age of 37 years (range 21-42). The patients
      can be divided into four subgroups [left-sided lesions (n = 4), right-sided
      lesions (n = 3), systemic right ventricle (n = 5) and Fontan circulation (n =
      2)]. Surgical procedures performed were: relief of systemic
      obstructive/regurgitant lesions +/- endocardial fibroelastosis resection (n = 4,
      three pulmonary vascular resistance >6 Wood units), correction of right-sided
      regurgitant/stenotic lesions (n = 3), ventricular assist device for patients with
      a systemic right ventricle (n = 5) and re-fashioning of the Fontan pathway (n =
      2). There were two early (5 and 30 days) and three late deaths (64, 232 and 374
      days) with a 1-year mortality of 28%. None of the deaths occurred in patients
      with a two-ventricle circulation and atrio-ventricular concordance. Nine patients
      are alive at a median of 433 days (range 204-2456). The New York Heart
      Association class has improved in all survivors by at least one class at 3 and 6
      months (P = 0.004 and 0.003). CONCLUSIONS: Alternative cardiac surgery can be
      undertaken in selected patients with ACHD referred for cardiopulmonary
      transplantation with a low mortality in patients with two ventricles and a
      systemic left ventricle. Ventricular assist devices carry a significant mortality
      in patients with a systemic right ventricle, although this offers a valuable
      palliation when there are no other options. The medium and long-term results are
      awaited.

PMID- 22588033
TI  - Preoperative pulmonary rehabilitation in patients with lung cancer and chronic
      obstructive pulmonary disease.
AB  - OBJECTIVES: Impaired cardiopulmonary reserve is the main cause of inoperability
      in non-small-cell lung cancer (NSCLC). This study aims to evaluate the role of a
      preoperative pulmonary rehabilitation (PPR) programme in the improvement of
      functional parameters, which can enable an increase in the number of patients
      eligible for surgery. METHODS: From January 2008 to June 2011, we observed a
      uniform group of 27 patients with NSCLC and chronic obstructive pulmonary disease
      (COPD). It showed: (i) a body mass index of 21.5 +/- 2 kg/m2;; (ii) forced
      expiratory volume in 1 s (FEV(1)) of 1.14 +/- 0.7 l; (iii) maximal peak of oxygen
      consumption (VO(2)max) of 12.9 +/- 1.8 ml/kg/min; (iv) carbon monoxide diffusing
      capacity (DLCO) of 72 +/- 3% predicted; (v) stage IB of lung cancer. All patients
      underwent a 4-week PPR programme, 6 days a week and were re-evaluated before
      inclusion for surgery. RESULTS: The rehabilitation programme was completed by all
      patients and extended by 2 weeks in nine patients, in order to obtain a further
      functional improvement. A statistically significant increase has been in the
      values of PaO(2) (60 +/- 10 vs 82 +/- 12 mmHg), of VO(2)max (12.9 +/- 1.8 vs 19.2
      +/- 2.1 ml/kg/min, P = 0.00001) and of FEV(1) (1.14 +/- 0.7 vs 1.65 +/- 0.8 l, P
      = 0.02). All patients underwent a lobectomy, with a postoperative morbidity of
      15%. CONCLUSIONS: A 4 to 6-week PPR programme prepares the NSCLC and COPD
      patients properly for the surgical approach, reducing the functional limitations
      of inoperability.

PMID- 22588034
TI  - Should methodological filters for diagnostic test accuracy studies be used in
      systematic reviews of psychometric instruments? A case study involving screening
      for postnatal depression.
AB  - BACKGROUND: Challenges exist when searching for diagnostic test accuracy (DTA)
      studies that include the design of DTA search strategies and selection of
      appropriate filters. This paper compares the performance of three MEDLINE search
      strategies for psychometric diagnostic test accuracy (DTA) studies in postnatal
      depression. METHODS: A reference set of six relevant studies was derived from a
      forward citation search via Web of Knowledge. The performance of the 'target
      condition and index test' method recommended by the Cochrane DTA Group was
      compared to two alternative strategies which included methodological filters.
      Outcome measures were total citations retrieved, sensitivity, precision and
      associated 95% confidence intervals (95%CI). RESULTS: The Cochrane recommended
      strategy and one of the filtered search strategies were equivalent in performance
      and both retrieved a total of 105 citations, sensitivity was 100% (95% CI 61%,
      100%) and precision was 5.2% (2.6%, 11.9%). The second filtered search retrieved
      a total of 31 citations, sensitivity was 66.6% (30%, 90%) and precision was 12.9%
      (5.1%, 28.6%). This search missed the DTA study with most relevance to the DTA
      review. CONCLUSIONS: The Cochrane recommended search strategy, 'target condition
      and index test', method was pragmatic and sensitive. It was considered the
      optimum method for retrieval of relevant studies for a psychometric DTA review
      (in this case for postnatal depression). Potential limitations of using filtered
      searches during a psychometric mental health DTA review should be considered.

PMID- 22588036
TI  - Current management of infantile hemangiomas and their common associated
      conditions.
AB  - This article reviews the most current practice guidelines in the diagnosis and
      treatment of infantile hemangiomas. Several systemic conditions that can be
      associated with hemangiomas, such as PHACES syndrome, are also discussed.
      Propranolol has become an effective first-line treatment, and protocols for its
      use as well as its potential risks are outlined.

PMID- 22588037
TI  - Otolaryngologic manifestations of craniofacial syndromes.
AB  - This review describes important aspects of the most commonly encountered
      craniofacial syndromes. The goal is to provide otolaryngologists and other health
      care providers with critical information necessary to manage these patients
      appropriately. The algorithm provided in this article should be helpful in
      guiding the treatment of craniofacial patients based on their unique
      otolaryngologic characteristics. The principles highlighted in the algorithm can
      be applied to other craniofacial syndromes not addressed here, including Pierre
      Robin sequence and Down syndrome.

PMID- 22588035
TI  - The quality of research synthesis in surgery: the case of laparoscopic surgery
      for colorectal cancer.
AB  - BACKGROUND: Several systematic reviews and meta-analyses populate the literature
      on the effectiveness of laparoscopic surgery for colorectal cancer. The utility
      of this body of work is unclear. The objective of this study was to synthesize
      all such systematic reviews in terms of clinical effectiveness, to appraise their
      quality, and to determine whether areas of duplication exist across reviews.
      METHODS: Systematic reviews comparing laparoscopic and open surgery for
      colorectal cancer were identified using a comprehensive search protocol (1991 to
      2008). The primary outcome was overall survival. The methodological quality of
      reviews was appraised using the Assessment of Multiple Systematic Reviews
      (AMSTAR) instrument. Abstraction and quality appraisal was carried out by two
      independent reviewers. Reviews were synthesized, and outcomes were compared
      qualitatively. A citation analysis was carried out using simple matrices to
      assess the comprehensiveness of each review. RESULTS: In total, 27 reviews were
      included; 13 reviews included only randomized controlled trials. Rectal cancer
      was addressed exclusively by four reviews. There was significant overlap between
      review purposes, populations and, outcomes. The mean AMSTAR score (out of 11) was
      5.8 (95% CI: 4.6 to 7.0). Overall survival was evaluated by ten reviews, none of
      which found a significant difference. Three reviews provided a selective meta
      analysis of time-to-event data. Previously published systematic reviews were
      poorly and highly selectively referenced (mean citation ratio 0.16, 95% CI: 0.093
      to 0.22). Previously published trials were not comprehensively identified and
      cited (mean citation ratio 0.56, 95% CI: 0.46 to 0.65). CONCLUSIONS: Numerous
      overlapping systematic reviews of laparoscopic and open surgery for colorectal
      cancer exist in the literature. Despite variable methods and quality, survival
      outcomes are congruent across reviews. A duplication of research efforts appears
      to exist in the literature. Further systematic reviews or meta-analyses are
      unlikely to be justified without specifying a significantly different research
      objective. This works lends support to the registration and updating of
      systematic reviews.

PMID- 22588038
TI  - Otolaryngologic manifestations of skeletal dysplasias in children.
AB  - This article reviews some of the otolaryngologic manifestations of skeletal
      dysplasias. Achondroplasia is discussed most comprehensively. Skeletal dysplasias
      are bone and cartilage disorders that disrupt the development of the long bones,
      craniofacial skeleton, and vertebral column, with the most notable characteristic
      being short stature. Children with skeletal dysplasias have various medical
      problems. These children often develop head and neck manifestations of their
      disorders. Hearing loss, middle ear disease, and respiratory difficulties are
      seen in these children. Otolaryngologists must be knowledgeable about these
      disorders to diagnose, treat, and appropriately refer children with skeletal
      dysplasias.

PMID- 22588039
TI  - The otolaryngologist's approach to the patient with Down syndrome.
AB  - As more patients with Down syndrome are living into adulthood, attention has
      focused on health factors that affect the quality of the patient's life and their
      ability to reach full potential. Patients with Down syndrome have several
      morphologic abnormalities that predispose them to problems with the ear, nose,
      and throat, and appropriate treatment can have a significant impact on the
      quality of life of these patients. Otolaryngologists are likely to see many
      patients with Down syndrome throughout their careers. This article reviews the
      literature to provide information and recommendations regarding management of
      Down syndrome.

PMID- 22588040
TI  - Allergic fungal sinusitis in children.
AB  - Allergic fungal sinusitis (AFS) is a subtype of eosinophilic chronic
      rhinosinusitis (CRS) characterized by type I hypersensitivity, nasal polyposis,
      characteristic computed tomography scan findings, eosinophilic mucus, and the
      presence of fungus on surgical specimens without evidence of tissue invasion.
      This refractory subtype of CRS is of the great interest in the pediatric
      population, given the relatively early age of onset and the difficulty in
      managing AFS through commercially available medical regimens. Almost universally,
      a diagnosis of AFS requires operative intervention. Postoperative adjuvant
      medical therapy is a mainstay in the treatment paradigm of pediatric AFS.

PMID- 22588041
TI  - Multisystem disease and pediatric laryngotracheal reconstruction.
AB  - Laryngotracheal reconstruction can be technically challenging. Successfully
      managing the patient's medical comorbidities is essential. Children undergoing
      laryngotracheal reconstruction rarely present with isolated subglottic stenosis;
      many have associated multisystem disorders. Effectively managing the patient
      enables successful outcomes after airway reconstruction.

PMID- 22588042
TI  - A review of the evaluation and management of velopharyngeal insufficiency in
      children.
AB  - This article highlights the most common causes of velopharyngeal insufficiency
      (VPI), and discusses routine evaluation and treatment algorithms for the
      management of VPI in children. VPI is a multifactorial condition that occurs
      commonly in syndromic and non-syndromic children. The most common features of VPI
      are audible hypernasal speech, facial grimacing, decreased speech
      intelligibility, nasal regurgitation, and nasal emission from failure to produce
      oronasal separation. Work-up of VPI typically involves radiologic and endoscopic
      testing performed with the assistance of a speech-language pathologist.
      Management of VPI involves initial speech therapy followed by operative repair
      with sphincter or pharyngeal flap pharyngoplasty, if needed.

PMID- 22588044
TI  - Pierre Robin Sequence: evaluation, management, indications for surgery, and
      pitfalls.
AB  - This article reviews the various treatment methods for airway obstruction and
      feeding difficulty in infants with Pierre Robin Sequence (PRS), and highlights
      the benefits and limitations of early mandibular distraction osteogenesis in
      particular as a way of managing both airway obstruction and feeding difficulty in
      these children.

PMID- 22588045
TI  - Endoscopic skull base techniques for juvenile nasopharyngeal angiofibroma.
AB  - This review focuses on the anatomy and techniques for endoscopic resection of
      juvenile nasopharyngeal angiofibroma (JNA), as well as adjunctive and potential
      alternative treatments. JNA is a benign but locally aggressive vascular tumor
      that primarily affects adolescent boys. Traditionally, these tumors have been
      removed via open surgical approaches. Recent advances in endoscopic equipment and
      techniques have enabled the endoscopic surgical excision of these tumors with
      favorable outcomes and decreased morbidity. At our institution as at others, we
      have achieved successful outcomes with transnasal endoscopic resection of JNA,
      including tumors with significant extension into adjacent compartments.

PMID- 22588046
TI  - Treating common disorders in complex children.

PMID- 22588043
TI  - Recurrent respiratory papillomatosis.
AB  - Recurrent respiratory papillomatosis (RRP) is a rare, benign disease with no
      known cure. RRP is caused by infection of the upper aerodigestive tract with the
      human papillomavirus (HPV). Passage through the birth canal is thought to be the
      initial transmission event, but infection may occur in utero. HPV vaccines have
      helped to provide protection from cervical cancer; however, their role in the
      prevention of RRP is undetermined. Clinical presentation of initial symptoms of
      RRP may be subtle. RRP course varies, and current management focuses on surgical
      debulking of papillomatous lesions with or without concurrent adjuvant therapy.

PMID- 22588047
TI  - Acute dietary nitrate supplementation improves dry static apnea performance.
AB  - Acute dietary nitrate (NO3-) supplementation has been reported to lower resting
      blood pressure, reduce the oxygen (O2) cost of sub-maximal exercise, and improve
      exercise tolerance. Given the proposed effects of NO3- on tissue oxygenation and
      metabolic rate, it is possible that NO3- supplementation might enhance the
      duration of resting apnea. If so, this might have important applications both in
      medicine and sport. We investigated the effects of acute NO3- supplementation on
      pre-apnea blood pressure, apneic duration, and the heart rate (HR) and arterial
      O2 saturation (SaO2) responses to sub-maximal and maximal apneas in twelve well
      trained apnea divers. Subjects were assigned in a randomized, double blind,
      crossover design to receive 70 ml of beetroot juice (BR; containing ~5.0 mmol of
      nitrate) and placebo juice (PL; ~0.003 mmol of nitrate) treatments. At 2.5 h post
      ingestion, the subjects completed a series of two 2-min (sub-maximal) static
      apneas separated by 3 min of rest, followed by a maximal effort apnea. Relative
      to PL, BR reduced resting mean arterial pressure by 2% (PL: 86+/-7 vs. BR: 84 +/-
      6 mmHg; P=0.04). The mean nadir for SaO2 after the two sub-maximal apneas was
      97.2+/-1.6% in PL and 98.5+/-0.9% in BR (P=0.03) while the reduction in HR from
      baseline was not significantly different between PL and BR. Importantly, BR
      increased maximal apneic duration by 11% (PL: 250 +/- 58 vs. BR: 278+/-64s;
      P=0.04). In the longer maximal apneas in BR, the magnitude of the reductions in
      HR and SaO2 were greater than in PL (P <= 0.05). The results suggest that acute
      dietary NO3- supplementation may increase apneic duration by reducing metabolic
      costs.

PMID- 22588048
TI  - Image-based vessel-by-vessel analysis for red blood cell and plasma dynamics with
      automatic segmentation.
AB  - The aim of the present study was to test the hypothesis that vascular tones of
      cortical surface and parenchymal blood flow can be dissociated depending on the
      perturbation. To this end, a novel image-based analytical method for
      quantitatively measuring vessel diameters and flow dynamics was developed. The
      algorithm relies on the spatiotemporal coherence of the pixel intensity changes
      induced by the transit of the fluorescent signals measured using confocal laser
      scanning fluorescent microscopy in the rat cerebral cortex. A cocktail of
      fluorescently labeled red blood cell (RBC) and plasma agents was administered to
      simultaneously compare RBC and plasma dynamics in the same vascular networks. The
      time to fluorescent signal appearance and the width of the fluorescent signal
      were measured in each segment and compared between sodium nitroprusside-induced
      global and sensory stimulation-induced local perturbation conditions. We observed
      that infusion of sodium nitroprusside induced significant vasodilation in the
      surface artery, particularly in the small arteries (1.8-fold increase).
      Vasodilation induced by sensory stimulation was observed to depend on vessel
      size, but significant changes were only detected for the small arteries and
      veins. Measurements of the time to venous appearance revealed that appearance
      time was extended by sodium nitroprusside, but shortened during forepaw
      stimulation, relative to the control condition. Both perturbations provoked the
      largest changes between the small artery and vein segments, indicating that the
      changes in the appearance time originate from blood passage through parenchymal
      microcirculation. These findings support the hypothesis that cortical surface
      vascular tone and parenchymal blood flow are individually coordinated.

PMID- 22588049
TI  - Evaluation of the antinociceptive, anti-inflammatory and gastric antiulcer
      activities of the essential oil from Piper aleyreanum C.DC in rodents.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Piper aleyreanum is a small tree that is widely
      distributed in tropical and subtropical regions, mostly in North and South
      America, and is used as an immunomodulator, analgesic and antidepressant in folk
      medicine. AIM OF THE STUDY: This study was designed to investigate the
      antinociceptive, anti-inflammatory and gastric antiulcer activities of the
      essential oils from the aerial parts of Piper aleyreanum (EOPa) in rodents.
      MATERIALS AND METHODS: The antinociceptive and anti-inflammatory effects of
      orally administered EOPa were evaluated in mice subjected to the formalin and
      pleurisy models, respectively. We also pretreated the rats with EOPa before acute
      ethanol-induced gastric lesions and measured gastric lesion extension and mucus
      and glutathione (GSH) levels in the gastric mucosa. Finally, we performed a
      phytochemical analysis of EOPa. RESULTS: The chemical composition of EOPa was
      analyzed by gas chromatography and mass spectrometry (GC/MS), which identified 35
      compounds, representing 81.7% of total oil compounds. Caryophyllene oxide
      (11.5%), beta-pinene (9%), spathulenol (6.7%), camphene (5.2%), beta-elemene
      (4.7%), myrtenal (4.2%), verbenone (3.3%) and pinocarvone (3.1%) were the major
      oil constituents. The oral administration of EOPa (10-1000 mg/kg) significantly
      inhibited the neurogenic and inflammatory phases of formalin-induced licking,
      with ID50 values of 281.2 and 70.5 mg/kg, respectively. The antinociception
      caused by EOPa (100 mg/kg, p.o.) was not reversed by naloxone (1 or 5 mg/kg,
      i.p.) in the formalin test. EOPa (100-300 mg/kg, p.o.) did not affect animal
      motor coordination in an open-field model. In carrageenan-induced pleurisy, EOPa
      (1-100 mg/kg, p.o.) significantly decreased the total cell count, neutrophils and
      mononuclear cells with mean ID50 values of 53.6, 21.7 and 43.5 mg/kg,
      respectively. In addition, EOPa (1-30 mg/kg, p.o.) protected the rats against
      ethanol-induced gastric lesions with an ID50 value of 1.7 mg/kg and increased the
      mucus and GSH levels of the gastric mucosa to levels similar to those of the non
      lesioned group. CONCLUSIONS: These data show for the first time that EOPa has
      significant antinociceptive and anti-inflammatory actions, which do not appear to
      be related to the opioid system. EOPa also has interesting gastroprotective
      effects related to the maintenance of protective factors, such as mucus
      production and GSH. These results support the widespread use of Piper aleyreanum
      in popular medicine and demonstrate that this plant has therapeutic potential for
      the development of phytomedicines with antinociceptive, anti-inflammatory and
      gastroprotective properties.

PMID- 22588050
TI  - Evolution and diversification of Group 1 [NiFe] hydrogenases. Is there a
      phylogenetic marker for O(2)-tolerance?
AB  - Group 1 hydrogenases are periplasmic enzymes and are thus strongly affected by
      the "outside world" the cell experiences. This exposure has brought about an
      extensive heterogeneity in their cofactors and redox partners. Whereas in their
      majority they are very O(2)-sensitive, several enzymes of this group have been
      recently reported to be O(2)-tolerant. Structural and biochemical studies have
      shown that this O(2)-tolerance is conferred by the presence of an unusual iron
      sulfur cofactor with supernumerary cysteine ligation (6 instead of 4 Cys, hence
      called '6C cluster'). This atypical cluster coordination affords redox plasticity
      (i.e. two-redox transitions), unprecedented for this type of cofactors and likely
      involved in resistance to O(2). Genomic screening and phylogenetic tree
      reconstruction revealed that 6C hydrogenases form a monophyletic clade and are
      unexpectedly widespread among bacteria. However, several other well-defined
      clades are observed, which indicate early diversification of the enzyme into
      different subfamilies. The various idiosyncrasies thereof are shown to comply
      with a very simple rule: phylogenetic grouping of hydrogenases directly
      correlates with their specific functions and hence biochemical characteristics.
      The observed variability results from gene duplication, gene shuffling and
      subsequent adaptation of the diversified enzymes to specific environments. An
      important factor for this diversification seems to have been the emergence of
      molecular oxygen. Hydrogenases appear to have dealt with oxidative stress in
      various ways, the most successful of which, however, was the innovation of the 6C
      cluster conferring pronounced O(2)-tolerance to the parent enzymes.

PMID- 22588051
TI  - An increased incidence of Hodgkin's lymphoma in patients with adult-onset
      sarcoma.
AB  - BACKGROUND: Sarcomas are rare, often fatal malignancies of connective tissues
      that can occur in genetic predisposition syndromes or result from carcinogen
      exposure. Hodgkin's lymphoma (HL) is not known to contribute to any recognised
      familial cancer syndrome comprising sarcomas, but is known to be associated with
      a variety of second cancers, including sarcomas. This study describes the
      prevalence of HL in families affected by sarcoma. METHODS: The International
      Sarcoma Kindred Study (ISKS) is a prospective cohort of 561 families ascertained
      via a proband with adult-onset sarcoma. Cancer-specific standardised incidence
      ratios (SIR) for multiple primary malignancies in probands were estimated.
      Clinical characteristics of individuals reporting both sarcoma and HL were
      described. Standardised incidence ratios for the occurrence of cancer in ISKS
      families were also estimated. RESULTS: Multiple primary cancers were reported in
      16% of probands, significantly higher than in the general population. The risk of
      HL in probands was increased 15.8-fold (95%CI 7.9-31.6) and increased risks were
      also seen for breast cancer (SIR 2.9, 95%CI 1.9-4.4) and thyroid cancer (SIR 8.4,
      95%CI 4.2-16.8). In 8 probands with both HL and sarcoma, the diagnosis of HL
      preceded that of sarcoma in 7 cases, and occurred synchronously in one case. Only
      3 cases of sarcoma occurred in or close to prior radiotherapy fields. The overall
      incidence of HL in the ISKS cohort was not significantly increased by comparison
      with age- and gender-specific population estimates (SIR 1.63, 95%CI 1.05-2.43),
      suggesting that the association between HL and sarcomas did not extend to other
      family members. The age of onset of non-sarcoma, non-HL cancers in families
      affected by both HL and sarcoma was younger than the general population (56.2 y
      vs 65.6 y, P < 0.0001). CONCLUSIONS: The basis for the association between HL and
      sarcomas may include the carcinogenic effects of therapy combined with excellent
      survival rates for HL. Common risk factors for both may also exist, including
      both environmental and heritable factors.

PMID- 22588052
TI  - A Web-based archive of systematic review data.
AB  - Systematic reviews have become increasingly critical to informing healthcare
      policy; however, they remain a time-consuming and labor-intensive activity. The
      extraction of data from constituent studies comprises a significant portion of
      this effort, an activity which is often needlessly duplicated, such as when
      attempting to update a previously conducted review or in reviews of overlapping
      topics.In order to address these inefficiencies, and to improve the speed and
      quality of healthcare policy- and decision-making, we have initiated the
      development of the Systematic Review Data Repository, an open collaborative Web
      based repository of systematic review data. As envisioned, this resource would
      serve as both a central archive and data extraction tool, shared among and freely
      accessible to organizations producing systematic reviews worldwide. A suite of
      easy-to-use software tools with a Web frontend would enable researchers to
      seamlessly search for and incorporate previously deposited data into their own
      reviews, as well as contribute their own.In developing this resource, we
      identified a number of technical and non-technical challenges, as well as devised
      a number of potential solutions, including proposals for systems and software
      tools to assure data quality, stratify and control user access effectively and
      flexibly accommodate all manner of study data, as well as means by which to
      govern and foster adoption of this new resource.Herein we provide an account of
      the rationale and development of the Systematic Review Data Repository thus far,
      as well as outline its future trajectory.

PMID- 22588053
TI  - Effect of Zn impurity in K0.8Fe(2-delta-x)Zn(x)Se2.
AB  - A series of K(0.8)Fe(2-delta-x)Zn(x)Se(2) single-crystal samples with nominal
      compositions 0 <= x <= 0.05 were grown and their physical properties were
      measured in order to study the effect of Zn impurity. It is found that the Zn
      impurity (x <= 0.02) does not affect the superconducting transition temperature
      T(c) significantly. Meanwhile the hump in resistivity which corresponds to the
      transition from the insulating to metallic phase quickly shifts towards low
      temperatures. The results imply that there should be a phase separation in this
      system and Zn impurity causes the enhancement of the insulating phase. The
      negligible effect of Zn impurity on T(c) suggests an s-wave pairing in the
      superconducting phase. Meanwhile there is a possibility that the Zn impurity may
      selectively enter into the insulting phase.

PMID- 22588054
TI  - Regulation of tumor initiation and metastatic progression by Eph receptor
      tyrosine kinases.
AB  - In recent years, a growing body of evidence has indicated that signaling
      molecules previously implicated in axon guidance are important regulators of
      multistep tumorigenesis and progression. Eph receptors and ephrins belong to this
      special class of molecules that play important roles in both axon guidance and
      cancer. Tremendous progress has been made in the past few years in both
      understanding the role of Eph receptors and ephrins in cancer and designing
      therapeutic strategies for cancer therapy. This review will focus on new advances
      in elucidating the contribution of Eph/ephrin molecules to key processes in tumor
      initiation and metastatic progression, including cancer cell proliferation,
      invasion and metastasis, and tumor angiogenesis.

PMID- 22588056
TI  - Semaphorin signals tweaking the tumor microenvironment.
AB  - Solid tumors not only comprise malignant cells but also other nonmalignant cell
      types, forming a unique microenvironment that can strongly influence the behavior
      of tumor cells. Recent advances in the understanding of cancer biology have
      highlighted the functional role of semaphorins. In fact, semaphorins form a
      family of molecular signals known to guide and control cell migration during
      embryo development and in adults. Tumor cells express semaphorins as well as
      their receptors, plexins and neuropilins. It has been shown that semaphorin
      signaling can regulate tumor cell behavior. Moreover, semaphorins are important
      regulators of tumor angiogenesis. Conversely, very little is known about the
      functional relevance of semaphorin signals for tumor-infiltrating stromal cells,
      such as leukocytes. In this chapter, we review the current knowledge on the
      functional role of semaphorins in cancer progression, and we focus on the
      emerging role of semaphorins in mediating the cross talk between tumor cells and
      different tumor stromal cells.

PMID- 22588057
TI  - Guidance for life, cell death, and colorectal neoplasia by netrin dependence
      receptors.
AB  - This review is focusing on a critical mediator of embryonic and postnatal
      development with multiple implications in inflammation, neoplasia, and other
      pathological situations in brain and peripheral tissues. These morphogenetic
      guidance and dependence processes are involved in several malignancies targeting
      the epithelial and immune systems including the progression of human colorectal
      cancers. We consider the most important findings and their impact on basic,
      translational, and clinical cancer research. Expected information can bring new
      cues for innovative, efficient, and safe strategies of personalized medicine
      based on molecular markers, protagonists, signaling networks, and effectors
      inherent to the Netrin axis in pathophysiological states.

PMID- 22588055
TI  - Essential roles of EphB receptors and EphrinB ligands in endothelial cell
      function and angiogenesis.
AB  - Eph receptor tyrosine kinases and their Ephrin ligands represent an important
      signaling system with widespread roles in cell physiology and disease. Receptors
      and ligands in this family are anchored to the cell surface; thus Eph/Ephrin
      interactions mainly occur at sites of cell-to-cell contact. EphB4 and EphrinB2
      are the Eph/Ephrin molecules that play essential roles in vascular development
      and postnatal angiogenesis. Analysis of expression patterns and function has
      linked EphB4/EphrinB2 to endothelial cell growth, survival, migration, assembly,
      and angiogenesis. Signaling from these molecules is complex, with the potential
      for being bidirectional, emanating both from the Eph receptors (forward
      signaling) and from the Ephrin ligands (reverse signaling). In this review, we
      describe recent advances on the roles of EphB/EphrinB protein family in
      endothelial cell function and outline potential approaches to inhibit
      pathological angiogenesis based on this understanding.

PMID- 22588059
TI  - Role of the VEGF/VEGFR axis in cancer biology and therapy.
AB  - New vessel formation (angiogenesis) is an essential physiological process for
      embryologic development, normal growth, and tissue repair. Angiogenesis is
      tightly regulated at the molecular level; however, this process is dysregulated
      in several pathological conditions such as cancer. The imbalance between pro- and
      antiangiogenic signaling molecules within tumors creates an abnormal vascular
      network that is characterized by dilated, tortuous, and leaky vessels. The
      pathophysiological consequences of these vascular abnormalities include temporal
      and spatial heterogeneity in tumor blood flow, oxygenation, and increased tumor
      interstitial fluid pressure. The resultant microenvironment deeply impacts on
      tumor progression, and also leads to a reduction in therapy efficacy. The
      discovery of vascular endothelial growth factor (VEGF) as a major driver of tumor
      angiogenesis has led to efforts to develop novel therapeutics aimed at inhibiting
      its activity. Anti-VEGF therapy has become an important option for the management
      of several human malignancies; however, a significant number of patients do not
      respond to anti-VEGF therapy when used either as single agent or in combination
      with chemotherapy. In addition, the benefit of antiangiogenic therapy is
      relatively short lived and the majority of patients relapse and progress. An
      increasing amount of reports suggest several potential mechanisms of resistance
      to antiangiogenic therapy including, but not limited to, tumor hypoxia. This
      chapter discusses the role of the VEGF axis in tumor biology and highlights the
      clinical application of anti-VEGF therapies elaborating on pitfalls and
      strategies to improve clinical outcome.

PMID- 22588060
TI  - Human cancer. Preface.

PMID- 22588058
TI  - A roundabout way to cancer.
AB  - The Slit family of secreted proteins and their transmembrane receptor, Robo, were
      originally identified in the nervous system where they function as axon guidance
      cues and branching factors during development. Since their discovery, a great
      number of additional roles have been attributed to Slit/Robo signaling, including
      regulating the critical processes of cell proliferation and cell motility in a
      variety of cell and tissue types. These processes are often deregulated during
      cancer progression, allowing tumor cells to bypass safeguarding mechanisms in the
      cell and the environment in order to grow and escape to new tissues. In the past
      decade, it has been shown that the expression of Slit and Robo is altered in a
      wide variety of cancer types, identifying them as potential therapeutic targets.
      Further, studies have demonstrated dual roles for Slits and Robos in cancer,
      acting as both oncogenes and tumor suppressors. This bifunctionality is also
      observed in their roles as axon guidance cues in the developing nervous system,
      where they both attract and repel neuronal migration. The fact that this
      signaling axis can have opposite functions depending on the cellular circumstance
      make its actions challenging to define. Here, we summarize our current
      understanding of the dual roles that Slit/Robo signaling play in development,
      epithelial tumor progression, and tumor angiogenesis.

PMID- 22588061
TI  - Advanced glycation end product associated skin autofluorescence: a mirror of
      vascular function?
AB  - Advanced glycation end products (AGEs) seem to be involved in aging as well as in
      the development of cardiovascular diseases. During aging, AGEs accumulate in
      extracellular matrix proteins like collagen and contribute to vessel stiffness.
      Whether non-invasive measurement of AGE accumulation in the skin may reflect
      vessel function and vessel protein modification is unknown. Herein we set out to
      analyze the AGE-modifications in the collagens extracted from residual bypass
      graft material, the skin autofluorescence reflecting the accumulation of AGEs in
      the body as well as the pulse wave velocity reflecting vessel stiffness. Collagen
      types I and III (pepsin digestible collagen fraction) were isolated from the
      veins of 52 patients by proteolysis. The residual collagen fraction was further
      extracted by collagenase digestion. Collagen was quantified by hydroxyproline
      assay and AGEs by the AGE intrinsic fluorescence. Skin autofluorescence was
      measured with an autofluorescence reader; pulse wave velocity with the VICORDER.
      The collagen AGE autofluorescence in patient vein graft material increased with
      patient age. The pepsin digestible collagen fraction was significantly less
      modified in comparison to the collagenase digestible fraction. Decreasing amounts
      of extracted collagenase digestible collagen correspond with increasing AGE
      autofluorescence. Skin autofluorescence and vessel stiffness were significantly
      linked to the AGE autofluorescence of the collagenase digestible collagen
      fraction from graft material. In conclusion we have found that skin
      autofluorescence and pulse wave velocity as non-invasive parameters significantly
      correlate with the AGE contained in graft material and therefore are strong
      predictors of vessel AGE modifications in patients with coronary heart disease.
      Whether the analysis of the skin autofluorescence leads to an improvement of the
      risk stratification in patients suffering from cardiovascular disease has to be
      further tested.

PMID- 22588062
TI  - Sodium nitrite de-stiffening of large elastic arteries with aging: role of
      normalization of advanced glycation end-products.
AB  - We tested the hypothesis that sodium nitrite treatment reverses large elastic
      artery stiffening in old mice via reductions in collagen I, increases in elastin
      and/or decreases in advanced glycation end products (AGEs) mediated by reduced
      oxidative stress. Aortic pulse wave velocity (aPWV), a measure of large elastic
      artery stiffness, was greater in old (26-28months) compared with young (4
      6months) control animals (520+/-9 vs. 405+/-6cm/s, p<0.05), and this was reversed
      by 3weeks of sodium nitrite treatment (50mg/L) (435+/-17cm/s). Age-related
      increases (p<0.05) in aortic superoxide production were associated with greater
      total and adventitial nitrotyrosine staining, all of which were reversed by
      nitrite treatment. Total and adventitial transforming growth factor beta and
      collagen I were increased, and total and medial elastin were reduced with aging
      (p<0.05), but were unaffected by sodium nitrite. Aorta from old mice had
      increased total, adventitial and medial AGEs (p<0.05 vs. young), which were
      normalized by sodium nitrite treatment. In aortic segments from young mice in
      vitro, pyrogallol (10MUM), a superoxide generator, induced an "aging-like"
      increase in AGEs, and direct treatment with AGEs induced vascular stiffening;
      these effects were prevented by incubation with sodium nitrite. De-stiffening of
      aged large elastic arteries by short-term sodium nitrite therapy is mediated in
      part by normalization of AGEs secondary to amelioration of oxidative stress.

PMID- 22588063
TI  - The superiority in voice processing of the blind arises from neural plasticity at
      sensory processing stages.
AB  - Blind people rely much more on voices compared to sighted individuals when
      identifying other people. Previous research has suggested a faster processing of
      auditory input in blind individuals than sighted controls and an enhanced
      activation of temporal cortical regions during voice processing. The present
      study used event-related potentials (ERPs) to single out the sub-processes of
      auditory person identification that change and allow for superior voice
      processing after congenital blindness. A priming paradigm was employed in which
      two successive voices (S1 and S2) of either the same (50% of the trials) or
      different actors were presented. Congenitally blind and matched sighted
      participants made an old-young decision on the S2. During the pre-experimental
      familiarization with the stimuli, congenitally blind individuals showed faster
      learning rates than sighted controls. Reaction times were shorter in person
      congruent trials than in person-incongruent trials in both groups. ERPs to S2
      stimuli in person-incongruent as compared to person-congruent trials were
      significantly enhanced at early processing stages (100-160 ms) in congenitally
      blind participants only. A later negative ERP effect (>200 ms) was found in both
      groups. The scalp topographies of the experimental effects were characterized by
      a central and parietal distribution in the sighted but a more posterior
      distribution in the congenitally blind. These results provide evidence for an
      improvement of early voice processing stages and a reorganization of the person
      identification system as a neural correlate of compensatory behavioral
      improvements following congenital blindness.

PMID- 22588064
TI  - A highly specific and discriminatory FISH assay for distinguishing between benign
      and malignant melanocytic neoplasms.
AB  - The diagnosis of certain melanocytic proliferations remains one of the most
      challenging areas in pathology. In recent times, fluorescence in situ
      hybridization (FISH) has emerged as a promising diagnostic aid to conventional
      microscopy. We previously showed that a 4-probe FISH assay targeting 6p25
      (RREB1), 6q23 (MYB), Cep6 (centromere 6), and 11q13 (CCND1) could discriminate
      between histologically unequivocal melanomas and benign nevi with a sensitivity
      of 86.7% and specificity of 95.4%. However, the sensitivity of the assay is
      approximately 70% in melanomas with spitzoid morphology. Furthermore,
      differentiating true gains from tetraploidy may cause difficulties in
      interpretation by inexperienced examiners. Here we refine the current probe set
      to better target spitzoid melanomas and more easily distinguish cells with
      imbalanced copy number aberrations from tetraploid cells. Using FISH data from 3
      training sets of 322 tumors, including 152 melanomas and 170 nevi, we identified
      9p21, 6p25, 11q13, and 8q24 as a probe set with improved discriminatory power in
      differentiating melanomas from nevi. In a validation set of 51 melanomas and 51
      nevi this probe set had a sensitivity of 94% and specificity of 98%, compared
      with the original probe set that had a sensitivity of 75% and specificity of 96%
      in the same validation cohort. We propose that by incorporating 9p21 into the 4
      probe FISH assay, with a new diagnostic algorithm, this new probe set would have
      improved discriminatory power in melanocytic neoplasms and improved sensitivity
      for detecting spitzoid melanomas, as demonstrated by our previous studies.

PMID- 22588065
TI  - Presence of a sarcomatous component outside the ovary is an adverse prognostic
      factor for primary ovarian malignant mixed mesodermal/mullerian tumors:  a
      clinicopathologic study of 47 cases.
AB  - Primary ovarian malignant mixed mesodermal tumors are uncommon. There exist few
      data in the literature on the significance of the sarcomatous component (SC) in
      these tumors. Here we investigated this aspect in 47 such tumors, with particular
      interest in whether the presence of SC outside the ovary confers a worse
      prognosis. We correlated various features of the SC (homologous vs. heterologous,
      type of heterologous SC, extent/percentage, mitotic count, necrosis, whether or
      not SC is present outside the ovary) with disease-specific survival (DSS) using
      the Kaplan-Meier method and log-rank test. We also correlated other
      clinicopathologic parameters with DSS: age, stage, tumor size, tumor laterality,
      type of the carcinomatous component (CC), lymph node status, vascular invasion,
      and degree of surgical debulking. The mean age was 69.0 years (range, 43 to 89
      y). The tumor was located in the left and right ovary in 18 and 24 patients,
      respectively (laterality could not be determined in 5 cases). The mean tumor size
      was 13.6 cm. Surgical debulking was optimal in 28, suboptimal in 6, and unclear
      in 13 patients. FIGO stage was I in 1 patient, II in 5 patients, III in 40 (IIIA
      in 1, IIIB in 11, IIIC in 28), and IV in 1 patient. Node metastasis and vascular
      invasion were noted in 6/17 and 29/47 patients, respectively. The mean percentage
      of SC was 29% (median 20%; range, 1% to 90%). The SC was heterologous in 34 (72%)
      and homologous in 13 (28%) patients. The mitotic figures per 10 HPF in SC were 33
      (0 to 128). Tumor necrosis was present in 45/47 cases (mean 10%; range, 1% to
      40%, only in CC in 14, only in SC in 2, in both SC and CC in 29). The CC was high
      grade serous in 27 patients, endometrioid in 2, mixed high-grade serous and
      endometrioid in 17, and mixed high-grade serous and clear cell carcinoma in 1
      patient. The extraovarian tumor contained only CC in 17 cases, only SC in 1 case,
      and both SC and CC in 28 cases. The median follow-up was 29 months (range, 1 to
      183 mo): 6 patients were lost to follow-up, 3 died postoperatively, 29 died from
      disease, 2 died from other causes, and 7 were still alive (14 to 183 mo). The DSS
      rate at 1, 2, and 5 years was 75%, 56%, and 21%, respectively. Presence of SC
      outside the ovary was a significant adverse prognostic factor (P=0.03), whereas
      other parameters were not. After adjusting for FIGO stage, presence of SC outside
      the ovary was still a significant adverse prognosticator for stage III patients
      (P=0.003), whereas others were not. Therefore, our findings showed that presence
      of SC outside the ovary was a significant adverse prognostic factor. We advocate
      listing the specific extraovarian tumor component (SC and/or CC) in the pathology
      report for primary ovarian malignant mixed mesodermal tumors.

PMID- 22588066
TI  - Endobronchial pulmonary angiomatoid fibrous histiocytoma: two cases with EWSR1
      CREB1 and EWSR1-ATF1 fusions.
AB  - Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue neoplasm of
      intermediate biological potential, predominantly occurring in the extremities of
      children and young adults. It has only recently been reported as a primary lung
      tumor. We describe 2 cases arising endobronchially harboring EWSR1 gene
      rearrangements by fluorescence in situ hybridization and, respectively, EWSR1
      CREB1 and EWSR1-ATF1 gene fusions by reverse transcription polymerase chain
      reaction. Histologically, both tumors showed classical features of AFH,
      comprising multiple nodules of bland spindle to epithelioid cells surrounded by
      lymphoplasmacytic inflammation and at least a partial fibrous capsule. Both
      tumors showed focal but strong desmin immunoreactivity, with focal pancytokeratin
      and epithelial membrane antigen in 1 case. The lung is now a recognized site of
      AFH occurrence, but tumors arising here can be associated with different gene
      fusions. It is important to recognize AFH in the pulmonary region, as its
      behavior at other sites is generally relatively indolent; however, it may be
      mistaken for metastatic or more aggressive primary lung tumors. It is likely that
      cases of AFH in the lung may have been previously missed because of their
      morphologic and genetic overlap with other pulmonary lesions.

PMID- 22588067
TI  - Podoplanin lymphatic density and invasion correlate with adverse
      clinicopathologic and biological factors and survival in neuroblastomas.
AB  - Neuroblastoma (NB) is a challenging problem in oncology, as the majority of
      patients have lymphatic and/or hematogenous metastases at diagnosis. We
      investigated the prognostic significance of lymphatic density (LD) and invasion
      (LI) in NBs using the lymphatic endothelial marker podoplanin (PDPN). A total of
      77 neuroblastic tumors and 9 ganglioneuromas (GNs) were immunostained for PDPN
      using D2-40 antibody. Intratumoral lymphatics were identified in 87% (67/77) of
      NBs and 7/9 GNs. The LD counts were significantly higher (P<0.01) in NBs
      (median=19.6, range=0.00 to 89.3) than in GNs (median=10.2, range=0 to 18.7). LI,
      assessed in D2-40-stained lymphatics, was present in 52/67 (78%) NBs. LDs were
      significantly higher in NBs from patients with adverse clinical factors (advanced
      stage, high-risk group, primary abdominal compared with extra-abdominal sites),
      biological factors (MYCN amplification, 1p deletion, 17q gain), and distant lymph
      node metastases. LDs and LI were also significantly higher in NBs belonging to an
      unfavorable pathology prognostic group and in those with a high mitosis
      karyorrhexis index. High LD and the presence of LI correlated with a shorter
      event-free survival in univariable analyses. High LD and the presence of LI were
      also associated with worse overall survival, although the association was less
      strong. In conclusion, increased LDs and the presence of LI correlated with
      adverse clinicopathologic and biological factors and survival. These findings
      suggest that PDPN has the potential to provide valuable prognostic information to
      clinicians for risk assessment in NBs.

PMID- 22588068
TI  - Histopathologic and ultrastructural features and claudin expression in papillary
      tumors of the pineal region:  a multicenter analysis.
AB  - Neuroepithelial papillary tumor of the pineal region (PTPR) has been defined as a
      distinct entity that is increasingly being recognized, with 96 cases now
      reported. This tumor shares morphologic features with both ependymomas and
      choroid plexus tumors. PTPR is characterized by an epithelial-like growth pattern
      in which the vessels are covered by layers of tumor cells forming perivascular
      pseudorosettes. These tumors exhibit various combinations of papillary and solid
      architecture, making the differential diagnosis of PTPR difficult to establish.
      We report the detailed description of the histopathologic features of a large
      series of PTPRs from 20 different centers and distinguish 2 subgroups of tumors
      with either a striking papillary growth pattern or a papillary and solid growth
      pattern. We highlight the findings that PTPRs have unusual vessels with multiple
      lumina and frequently show detachment of the border of the tumoral cells from the
      vascular wall. The 2 PTPR subgroups present similar clinical characteristics and
      immunophenotypes. We confirmed and extended the results of previous
      ultrastructural studies on the presence of intercellular junctions at the apical
      part of tumoral cells. The expression of the tight junction proteins claudin-1,
      claudin-2, and claudin-3 was investigated by immunohistochemistry. Claudin-1 and
      claudin-3, but not claudin-2, were expressed in PTPRs and in the fetal
      subcommissural organ, potentially the origin of this tumor. In contrast, all 3
      claudins were expressed in choroid plexus papillomas. Claudin expression may help
      in the diagnosis of PTPRs and can be used in combination with other markers, such
      as CK18, NCAM, E-cadherin, MAP-2, and Kir 7.1.

PMID- 22588069
TI  - Duodenal gastrinoma with multiple gastric neuroendocrine tumors secondary to
      chronic Helicobacter pylori gastritis.
AB  - Helicobacter pylori (HP) has been associated with neuroendocrine tumors of the
      stomach and duodenum. Gastric enterochromaffin-like (ECL) cell tumors and
      duodenal gastrinomas have also been associated with HP gastritis in separate
      series but have not been reported together. With other possible causes excluded,
      we present a patient with HP-associated atrophy of the oxyntic mucosa that
      ultimately resulted in stimulation and reactive hyperplasia of gastrin-producing
      cells in both the antrum and proximal duodenum, the latter progressing to
      formation of a gastrin-producing cell nodule (gastrinoma). Both of these sources
      of gastrin resulted in ECL hyperplasia in the atrophied oxyntic mucosa with
      progression to microcarcinoids and well-differentiated neuroendocrine tumors,
      along with hypertrophy of residual proximal gastric parietal cells. As atrophy
      tends to spread from the antrum proximally, residual oxyntic mucosa was still
      infected with HP and offers 1 explanation for the apparent paradox of atrophic
      gastritis with ECL hyperplasia and neoplasia in the distal oxyntic mucosa, with
      proximal oxyntic mucosa showing mild hypertrophic changes in a background of
      typical HP gastritis.

PMID- 22588070
TI  - Corneal reinforcement using an acellular dermal matrix for an analysis of
      biocompatibility, mechanical properties, and transparency.
AB  - The aim of this study was to analyze the viability of using an acellular dermal
      matrix (ADM) as a reinforcement material for peripheral corneal thinning disease.
      The complete removal of cell components was confirmed by hematoxylin and eosin
      (H&E) and 4',6-diamidino-2-phenylindole (DAPI) staining. Transmission electron
      microscopy determined that the stromal structure was well preserved. Uniaxial
      tests revealed that the ADM had strong mechanical properties. After being
      implanted into rabbit cornea the ADM showed no sign of rejection and even
      achieved good transparency 24weeks post-surgery. H&E staining demonstrated that
      keratocytes grew in the ADM and the ADM-cornea interface became blurry.
      Picrosirius red staining revealed great changes of collagen in the ADM. Uniaxial
      testing of the reinforced cornea showed better mechanical strength than the
      normal rabbit cornea, but this did not exhibit statistical significance. These
      results suggest that ADM is a worthy candidate for future exploration as a
      reinforcement material for peripheral corneal thinning problems.

PMID- 22588071
TI  - Cohesive behavior of soft biological adhesives: experiments and modeling.
AB  - Extracellular proteins play a key role in generating and maintaining cohesion and
      adhesion in biological tissues. These "natural glues" are involved in vital
      biological processes such as blood clotting, wound healing and maintaining the
      structural integrity of tissues. Macromolecular assemblies of proteins can be
      functionally stabilized in a variety of ways in situ that include ionic
      interactions as well as covalent crosslinking to form protein networks that can
      extend both within and between tissues. Within tissues, myriad cohesive forces
      are required to preserve tissue integrity and function, as are additional
      appropriate adhesive forces at interfaces both within and between tissues of
      differing composition. While the mechanics of some key structural adhesive
      proteins have been characterized in tensile experiments at both the macroscopic
      and single protein levels, the fracture toughness of thin proteinaceous
      interfaces has never been directly measured. Here, we describe a novel and simple
      approach to measure the cohesive behavior and toughness of thin layers of
      proteinaceous adhesives. The test is based on the standard double-cantilever beam
      test used for engineering adhesives, which was adapted to take into account the
      high compliance of the interface compared with the beams. This new "rigid double
      cantilever beam" method enables stable crack propagation through an interfacial
      protein layer, and provides a direct way to measure its full traction-separation
      curve. The method does not require any assumption of the shape of the cohesive
      law, and the results provide abundant information contributing to understanding
      the structural, chemical and molecular mechanisms acting in biological adhesion.
      As an example, results are presented using this method for thin films of fibrin-a
      protein involved in blood clotting and used clinically as a tissue bio-adhesive
      after surgery-with the effects of calcium and crosslinking by Factor XIII being
      examined. Finally, a simple model is proposed, demonstrating how a bell-shaped
      cohesive law forms during the failure of the fibrin interface based on an eight
      chain model whose structure degrades and changes configuration with stress.

PMID- 22588072
TI  - Bulk properties and bioactivity assessment of porous polymethylmethacrylate
      cement loaded with calcium phosphates under simulated physiological conditions.
AB  - Polymethylmethacrylate (PMMA) cements are widely used in spinal surgery.
      Nevertheless, these types of cements present some documented drawbacks.
      Therefore, efforts have been made to improve the properties and biological
      performance of solid PMMA. A porous structure would seem to be advantageous for
      anchoring purposes. This work studied the bulk physicochemical, mechanical and
      interconnectivity properties of porous PMMA cements loaded with various amounts
      of calcium phosphate (CaP). As a measure of bioactivity, changes of PMMA cements
      under simulated physiological conditions were studied in a calcium phosphate
      solution for 0, 3, 7, 14, 21 and 28 days. Scanning electron microscopy (SEM), X
      ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), micro
      computed tomography (MU-CT) and mechanical compression tests were performed to
      characterize the morphology, crystallographic and chemical composition,
      interconnectivity and mechanical properties, respectively. SEM allowed observing
      the result of loading CaP into the porous PMMA, which was corroborated by XRD,
      FTIR and MU-CT. No interference of the CaP with the PMMA was detected. MU-CT
      described similar interconnectivity and pore distribution for all CaP
      percentages. Mechanical properties were not significantly altered by the CaP
      percentages or the immersion time. Hence, porous PMMA was effectively loaded with
      CaP, which provided the material with properties for potential osteoconductivity.

PMID- 22588073
TI  - The microRNA expression signature on modified titanium implant surfaces
      influences genetic mechanisms leading to osteogenic differentiation.
AB  - Topographically and chemically modified titanium implants are recognized to have
      improved osteogenic properties; however, the molecular regulation of this process
      remains unknown. This study aimed to determine the microRNA profile and the
      potential regulation of osteogenic differentiation following early exposure of
      osteoprogenitor cells to sand-blasted, large-grit acid-etched (SLA) and
      hydrophilic SLA (modSLA) surfaces. Firstly, the osteogenic characteristics of the
      primary osteoprogenitor cells were confirmed using ALP activity and Alizarin Red
      S staining. The effect of smooth (SMO), SLA and modSLA surfaces on the TGF
      beta/BMP (BMP2, BMP6, ACVR1) and non-canonical WNT/Ca(2+) (WNT5A, FZD6) pathways,
      as well as the integrins ITGB1 and ITGA2, was determined. It was revealed that
      the modified titanium surfaces could induce the activation of TGF-beta/BMP and
      non-canonical WNT/Ca(2+) signaling genes. The expression pattern of microRNAs
      (miRNAs) related to cell differentiation was evaluated. Statistical analysis of
      the differentially regulated miRNAs indicated that 35 and 32 miRNAs were down
      regulated on the modSLA and SLA surfaces respectively, when compared with the
      smooth surface (SMO). Thirty-one miRNAs that were down-regulated were common to
      both modSLA and SLA. There were 10 miRNAs up-regulated on modSLA and nine on SLA
      surfaces, amongst which eight were the same as observed on modSLA. TargetScan
      predictions for the down-regulated miRNAs revealed genes of the TGF-beta/BMP and
      non-canonical Ca(2+) pathways as targets. This study demonstrated that modified
      titanium implant surfaces induce differential regulation of miRNAs, which
      potentially regulate the TGF-beta/BMP and WNT/Ca(2+) pathways during osteogenic
      differentiation on modified titanium implant surfaces.

PMID- 22588075
TI  - A subscapularis-preserving arthroscopic release of capsule in the treatment of
      internal rotation contracture of shoulder in Erb's palsy (SPARC procedure).
AB  - The purpose of this study was to evaluate a minimally invasive subscapularis
      preserving arthroscopic release of capsule in the treatment of internal rotation
      contracture of the shoulder due to Erb's palsy. We performed our procedure
      (subscapularis-preserving arthroscopic release of capsule) in 10 paediatric
      shoulders with an average age of 20.2 months and followed them for an average
      period of 41.5 months. All the patients were assessed clinically and
      radiologically preoperatively and postoperatively at regular intervals. The
      Mallet scoring system was used for analysing the results. The average gain in
      passive external rotation was 50 degrees . The active internal rotation was
      preserved in all the cases. With the mid-term follow-up, there was no loss of the
      gained external rotation or the recurrence of internal rotation contracture of
      the shoulder. Our hypothesis has achieved its goal in preserving subscapularis,
      active internal rotation and treatment of internal rotation contracture of the
      shoulder. The success of this procedure lies in the early identification of
      starting of internal rotation contracture and early surgical intervention to
      prevent progressive permanent glenohumeral osseocartilaginous deformity.

PMID- 22588074
TI  - Crosslinking and composition influence the surface properties, mechanical
      stiffness and cell reactivity of collagen-based films.
AB  - This study focuses on determining the effect of varying the composition and
      crosslinking of collagen-based films on their physical properties and interaction
      with myoblasts. Films composed of collagen or gelatin and crosslinked with a
      carbodiimide were assessed for their surface roughness and stiffness. These
      samples are significant because they allow variation of physical properties as
      well as offering different recognition motifs for cell binding. Cell reactivity
      was determined by the ability of myoblastic C2C12 and C2C12-alpha2+ cell lines
      (with different integrin expression) to adhere to and spread on the films.
      Significantly, crosslinking reduced the cell reactivity of all films,
      irrespective of their initial composition, stiffness or roughness. Crosslinking
      resulted in a dramatic increase in the stiffness of the collagen film and also
      tended to reduce the roughness of the films (R(q) = 0.417 +/- 0.035 MUm, E = 31
      +/- 4.4 MPa). Gelatin films were generally smoother and more compliant than
      comparable collagen films (R(q) = 7.9 +/- 1.5 nm, E = 15 +/- 3.1 MPa). The
      adhesion of alpha2-positive cells was enhanced relative to the parental C2C12
      cells on collagen compared with gelatin films. These results indicate that the
      detrimental effect of crosslinking on cell response may be due to the altered
      physical properties of the films as well as a reduction in the number of
      available cell binding sites. Hence, although crosslinking can be used to enhance
      the mechanical stiffness and reduce the roughness of films, it reduces their
      capacity to support cell activity and could potentially limit the effectiveness
      of the collagen-based films and scaffolds.

PMID- 22588076
TI  - Acute traumatic posterior elbow dislocation in children.
AB  - Traumatic posterior dislocation of the elbow is often associated with significant
      morbidity and incomplete recovery. The aim of this study was to retrospectively
      analyse the outcome of 33 children (median age 10.8 years). Patients underwent
      reduction and assessment of stability under general anaesthesia. Pure
      dislocations (n=10) were immobilized, whereas unstable fractures (n=23) were
      stabilized. Refixation of ligaments was performed if stability was not achieved
      by fracture stabilization alone. Immobilization was continued for 26 (pure
      dislocations) or 35 days (associated injuries), respectively. Results were
      excellent (n=9) or good (n=1) after pure dislocation. Results were excellent
      (n=15), good (n=7) or poor (n=1) in children with associated injuries. Accurate
      diagnosis, concentric stable reduction of the elbow as well as stable
      osteosynthesis of displaced fractures are associated with good results in
      children with acute posterior elbow dislocations.

PMID- 22588077
TI  - Expanding cytotoxic T lymphocytes from umbilical cord blood that target
      cytomegalovirus, Epstein-Barr virus, and adenovirus.
AB  - Virus infections after stem cell transplantation are among the most common causes
      of death, especially after cord blood (CB) transplantation (CBT) where the CB
      does not contain appreciable numbers of virus-experienced T cells which can
      protect the recipient from infection. We and others have shown that virus
      specific CTL generated from seropositive donors and infused to the recipient are
      safe and protective. However, until recently, virus-specific T cells could not be
      generated from cord blood, likely due to the absence of virus-specific memory T
      cells. In an effort to better mimic the in vivo priming conditions of naive T
      cells, we established a method that used CB-derived dendritic cells (DC)
      transduced with an adenoviral vector (Ad5f35pp65) containing the immunodominant
      CMV antigen pp65, hence driving T cell specificity towards CMV and adenovirus. At
      initiation, we use these matured DCs as well as CB-derived T cells in the
      presence of the cytokines IL-7, IL-12, and IL-15. At the second stimulation we
      used EBV-transformed B cells, or EBV-LCL, which express both latent and lytic EBV
      antigens. Ad5f35pp65-transduced EBV-LCL are used to stimulate the T cells in the
      presence of IL-15 at the second stimulation. Subsequent stimulations use
      Ad5f35pp65-transduced EBV-LCL and IL-2. From 50x10(6) CB mononuclear cells we are
      able to generate upwards of 150 x 10(6) virus-specific T cells that lyse antigen
      pulsed targets and release cytokines in response to antigenic stimulation. These
      cells were manufactured in a GMP-compliant manner using only the 20% fraction of
      a fractionated cord blood unit and have been translated for clinical use.

PMID- 22588078
TI  - Phenol levels during intralesional curettage and local adjuvant treatment of
      benign and low-grade malignant bone tumours.
AB  - BACKGROUND: Phenol is widely used for years as local adjuvant treatment for bone
      tumours. Despite its use for a long time, no information is available about the
      local concentration of phenol that is achieved in an individual patient, and the
      most sufficient and safe procedure to wash out the phenol after using it as local
      adjuvant. QUESTIONS/PURPOSES: 1. What is the initial local concentration of
      phenol in the tissue of the cavity wall after the application of phenol? 2. How
      quickly is phenol 85% diluted by washing the bone cavity with ethanol 96%
      solution? 3. Is the degree and speed of dilution influenced by the size of the
      cavity? 4. How many times should the cavity be rinsed to obtain sufficient
      elimination of phenol? METHODS: A basic science study was performed at
      respectively 16 and 10 patients, treated by intralesional curettage and adjuvant
      therapy for low-grade central chondrosarcoma of bone. Test 1:in 16 patients ten
      samples were collected of the mixture of phenol and ethanol from the bone cavity.
      Test 2:in ten patients, two biopsy samples were taken from the cavity wall in the
      bone during surgery. RESULTS: Phenol concentrations had wide variety in different
      patients, but all decreased by rinsing with ethanol. CONCLUSIONS: Ethanol 96% is
      effective to wash out local applicated phenol, by rinsing the bone cavity six
      times. The local concentration of phenol diminishes to an acceptable
      concentration of 0.2%. This study provides new insights to safely further improve
      the surgical technique of intralesional treatment of bone tumours.

PMID- 22588080
TI  - Innate immunity: regulation of caspases by IAP-dependent ubiquitylation.
AB  - Caspases are widely known as initiators and executioners of cell death. Full
      activation of caspases leading to cleavage of many cellular substrates was long
      considered to be a point-of-no-return in the apoptosis pathway. However, it also
      has been known that activated caspases do not always have the ability to kill,
      but instead initiate non-apoptotic processes such as cell differentiation or
      activation of innate immune responses. In this issue of The EMBO Journal,
      Meinander et al (2012) explore the contribution of polyubiquitination of Dredd, a
      known initiator caspase, to the activation of innate immunity. The authors show
      that infection with gram-negative bacteria leads to DIAP2-dependent
      ubiquitylation of Dredd which in turn is required for processing of Relish (Rel)
      and expression of antimicrobial peptide (AMP) genes that are indispensable for
      fighting the infection.

PMID- 22588079
TI  - miR-124-regulated RhoG reduces neuronal process complexity via ELMO/Dock180/Rac1
      and Cdc42 signalling.
AB  - The small GTPase RhoG plays a central role in actin remodelling during diverse
      biological processes such as neurite outgrowth, cell migration, phagocytosis of
      apoptotic cells, and the invasion of pathogenic bacteria. Although it is known
      that RhoG stimulates neurite outgrowth in the rat pheochromocytoma PC12 cell
      line, neither the physiological function nor the regulation of this GTPase in
      neuronal differentiation is clear. Here, we identify RhoG as an inhibitor of
      neuronal process complexity, which is regulated by the microRNA miR-124. We find
      that RhoG inhibits dendritic branching in hippocampal neurons in vitro and in
      vivo. RhoG also inhibits axonal branching, acting via an ELMO/Dock180/Rac1
      signalling pathway. However, RhoG inhibits dendritic branching dependent on the
      small GTPase Cdc42. Finally, we show that the expression of RhoG in neurons is
      suppressed by the CNS-specific microRNA miR-124 and connect the regulation of
      RhoG expression by miR-124 to the stimulation of neuronal process complexity.
      Thus, RhoG emerges as a cellular conductor of Rac1 and Cdc42 activity, in turn
      regulated by miR-124 to control axonal and dendritic branching.

PMID- 22588081
TI  - A dual function of Bcl11b/Ctip2 in hippocampal neurogenesis.
AB  - The development of the dentate gyrus is characterized by distinct phases
      establishing a durable stem-cell pool required for postnatal and adult
      neurogenesis. Here, we report that Bcl11b/Ctip2, a zinc finger transcription
      factor expressed in postmitotic neurons, plays a critical role during postnatal
      development of the dentate gyrus. Forebrain-specific ablation of Bcl11b uncovers
      dual phase-specific functions of Bcl11b demonstrated by feedback control of the
      progenitor cell compartment as well as regulation of granule cell
      differentiation, leading to impaired spatial learning and memory in mutants.
      Surprisingly, we identified Desmoplakin as a direct transcriptional target of
      Bcl11b. Similarly to Bcl11b, postnatal neurogenesis and granule cell
      differentiation are impaired in Desmoplakin mutants. Re-expression of Desmoplakin
      in Bcl11b mutants rescues impaired neurogenesis, suggesting Desmoplakin to be an
      essential downstream effector of Bcl11b in hippocampal development. Together, our
      data define an important novel regulatory pathway in hippocampal development, by
      linking transcriptional functions of Bcl11b to Desmoplakin, a molecule known to
      act on cell adhesion.

PMID- 22588082
TI  - Structure of human POFUT2: insights into thrombospondin type 1 repeat fold and O
      fucosylation.
AB  - Protein O-fucosylation is a post-translational modification found on
      serine/threonine residues of thrombospondin type 1 repeats (TSR). The fucose
      transfer is catalysed by the protein O-fucosyltransferase 2 (POFUT2) and >40
      human proteins contain the TSR consensus sequence for POFUT2-dependent
      fucosylation. To better understand O-fucosylation on TSR, we carried out a
      structural and functional analysis of human POFUT2 and its TSR substrate. Crystal
      structures of POFUT2 reveal a variation of the classical GT-B fold and identify
      sugar donor and TSR acceptor binding sites. Structural findings are correlated
      with steady-state kinetic measurements of wild-type and mutant POFUT2 and TSR and
      give insight into the catalytic mechanism and substrate specificity. By using an
      artificial mini-TSR substrate, we show that specificity is not primarily encoded
      in the TSR protein sequence but rather in the unusual 3D structure of a small
      part of the TSR. Our findings uncover that recognition of distinct conserved 3D
      fold motifs can be used as a mechanism to achieve substrate specificity by
      enzymes modifying completely folded proteins of very wide sequence diversity and
      biological function.

PMID- 22588083
TI  - Quantification of the humoral immune response and hemoplasma blood and tissue
      loads in cats coinfected with 'Candidatus Mycoplasma haemominutum' and feline
      leukemia virus.
AB  - 'Candidatus Mycoplasma haemominutum' (CMhm) is a hemotropic mycoplasma (aka
      hemoplasma) of domestic cats and wild felids. In a transmission study, we exposed
      eight specified pathogen-free cats to blood from Iberian lynxes (Lynx pardinus)
      infected with CMhm. The cats were coinfected with feline leukemia virus (FeLV)
      from an Iberian lynx or with a prototype FeLV. The goal of the present study was
      to quantify the humoral immune response to CMhm and to identify potential target
      tissues and sequestration sites. Antibodies were measured by a recombinant
      antigen-based enzyme-linked immunosorbent assay, and blood and tissue loads were
      quantified using real-time PCR. Seven out of eight cats became CMhm-infected; all
      of these cats seroconverted between 3 and 13 weeks after inoculation. Antibody
      levels correlated with the CMhm blood loads. The peak CMhm blood loads were
      inversely correlated with the incubation period. PCR-positive results were found
      in all 24 tissues tested but not for all samples. Although all tissues were PCR
      positive in one cat euthanized ten weeks after infection, many tissues tested
      negative in six cats euthanized at week 20 after infection. In several cats, the
      spleen, lung, liver, heart and aorta contained more copies than expected given
      the tissue's blood supply, but most tissues contained fewer copies than expected.
      In conclusion, this is the first study to quantify the humoral immune response
      and tissue loads in CMhm-FeLV-coinfected cats. The tissue loads appeared to
      correlate with the duration of infection and with the blood loads, but no
      evidence of significant CMhm tissue sequestration was found.

PMID- 22588084
TI  - Gap analysis survey: an aid in transitioning to standardized curricula for
      nuclear medicine technology.
AB  - This article discusses the process by which the Society of Nuclear Medicine
      Technology Section (SNMTS) is assisting educators as they transition to comply
      with the fourth edition of the Curriculum Guide for Educational Programs in
      Nuclear Medicine Technology. METHODS: An electronic survey was sent to a list of
      nuclear medicine technology programs compiled by the educational division of the
      SNMTS. The collected data included committee member demographics, goals and
      objectives, conference call minutes, consultation discussions, transition
      examples, 4- and 2-y program curricula, and certificate program curricula.
      RESULTS: There were 56 responses to the survey. All respondents were program
      directors, with 3 respondents having more than one type of program, for a total
      of 59 programs. Of these, 19 (33.93%) were baccalaureate, 19 (28.57%) associate,
      and 21 (37.5%) certificate. Forty-eight respondents (85.71%) had accreditation
      through the Joint Review Commission on Educational Programs in Nuclear Medicine
      Technology, 6 (10.71%) had regional accreditation, and 2 (3.57%) were accredited
      through other entities. Thirteen categories of required general education courses
      were identified, and the existing program curricula of 9 (69.2%) courses were
      more than 50% compliant with the fourth edition Curriculum Guide. The fact that
      no measurable gap could be found within the didactic professional content across
      programs was due to the lack of a degree requirement and content standardization
      within the profession. The data indicated that the participating programs offer a
      minimum of 1-15 contact hours in emerging technology modalities. The required
      clinical hours ranged from 765 to 1,920 for degree or certificate completion. The
      average number of clinical hours required for all programs was 1,331.69.
      CONCLUSION: Standardization of the number and types of courses is needed both for
      current baccalaureate programs and for clinical education. This standardization
      will guide programs in transitioning from a certificate or associate level to the
      baccalaureate level. The greatest obstacle is in expanding curricula to meet the
      recommendations of the fourth edition Curriculum Guide. Such expansion to entry
      level competency may be met by incorporating hybrid imaging courses, secondary
      level courses, and equivalency courses on the basic sciences and emerging
      technologies.

PMID- 22588085
TI  - Transport properties of diazonium functionalized graphene: chiral two-dimensional
      hole gases.
AB  - The electric transport properties of diazonium functionalized graphene (DFG) were
      investigated. The temperature dependence of the resistivity (rho-T) and the
      Shubnikov-de Haas oscillation of the DFG revealed two-dimensional hole gas (2DHG)
      behaviors. The DFGs exhibited unusual weak localization behaviors in which both
      inelastic and chirality-breaking elastic scattering processes should be taken
      into account, meaning that graphene chirality was maintained. Because of the
      giant decrease in the diffusion coefficient, the scattering rates remained
      relatively low in the presence of suppression of the scattering lengths. The
      decreases of both the mean free path and the Fermi velocity were responsible for
      the suppression of the diffusion coefficient and hence the charge mobility.

PMID- 22588086
TI  - Palpitations are predictive of future atrial fibrillation. An 11-year follow-up
      of 22,815 men and women: the Tromso Study.
AB  - BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia which
      increases morbidity and mortality. Identification of risk factors is therefore
      important. We examined the impact of palpitations and cardiovascular risk factors
      in prediction of AF (all types) and lone AF in a large population-based cohort.
      DESIGN: We carried out a prospective population-based cohort study. METHODS: A
      total of 22,815 participants from a population survey in 1994-1995 were followed
      up for a mean of 11.1 years. Mean age at baseline was 46 years. Measurements of
      height, weight, blood pressure, heart rate, total cholesterol and high-density
      lipoprotein (HDL)-cholesterol, and information on palpitations, diabetes, angina,
      myocardial infarction, and antihypertensive treatment were obtained at baseline.
      The outcome measure was first-ever AF, documented on an electrocardiogram. Cox
      proportional hazards regression model was used to estimate hazard ratios (HRs)
      for AF. RESULTS: Palpitations were associated with increased risk of AF in both
      women (HR 1.62, 95% confidence interval [CI] 1.29-2.02) and men (HR 1.91, 95% CI
      1.54-2.35). For hypertension the HR for AF was 1.98 (1.46-2.69) in women and 1.40
      (1.13-1.74) in men. The HR for 1 SD increase in body mass index (BMI) was 1.16
      (1.06-1.27) in women and 1.47 (1.32-1.63) in men. Body height and BMI were
      associated with increased risk for lone AF in men. CONCLUSION: Palpitations,
      hypertension and BMI were predictive of future atrial fibrillation in both sexes.

PMID- 22588087
TI  - Cardiovascular risk prediction in a population with the metabolic syndrome:
      Framingham vs. UKPDS algorithms.
AB  - BACKGROUND: Cardiovascular disease (CVD) risk-prediction algorithms are key in
      determining one's eligibility for prevention strategies, but are often population
      specific. Metabolic syndrome (MetS), a clustering of risk factors that increase
      the risk of CVD, does not currently have a risk-prediction algorithm available
      for prediction of CVD. The aim of this study was to compare the predictive
      capacities of an algorithm intended for 'healthy' individuals and one intended
      for 'diabetic' individuals. METHODS: Individual-specific data from 2700 subjects
      defined as MetS but free of diagnosed CVD from the Australian Diabetes, Obesity
      and Lifestyle study was used to estimate 5-year risk of CVD using the two
      algorithms, and compared using Wilcoxon-signed rank test. CVD end point data was
      used to assess the performance using discrimination and calibration techniques of
      the two algorithms. RESULTS: Five-year risk-prediction comparisons demonstrated
      that the UKPDS algorithm overpredicted risk in the younger age groups (25-54
      years) and underpredicted risk in the older age groups (>=55 years) compared to
      the Framingham algorithm. A total of 133 CVD events occurred over a median follow
      up of 5.0 years. Model performance analyses demonstrated both the Framingham and
      UKPDS algorithms were poor at discrimination (area under receiver operator curve
      0.513 and 0.524, respectively) and calibration (Hosmer-Lemeshow 467.1 and 297.0,
      respectively). CONCLUSIONS: Neither the Framingham or UKPDS algorithms are ideal
      for prediction of CVD risk in a MetS population. This study highlights the need
      for development of population-specific risk-prediction algorithms for this
      growing population group.

PMID- 22588088
TI  - A diastereoselective synthesis of 7alpha-nitromethyl steroid derivative and its
      use for an efficient synthesis of eplerenone.
AB  - A novel and efficient method of stereoselectively introducing alpha-nitromethyl
      group to C-7 position of 11alpha-hydroxyl canrenone 4 was described. In addition,
      this method was successfully applied in a total synthesis of Eplerenone 8. The
      route was characteristic of simple operation, moderate reaction conditions with 5
      steps and 55% total yield, at the same time, without any expensive or toxic
      reagent in use.

PMID- 22588089
TI  - Mussel-inspired load bearing metal-polymer glues.
AB  - A mussel-inspired synthetic adhesive based on dopamine containing methacrylate
      copolymers was developed to bond polymers to metal surfaces at an adhesion
      strength of up to 20 MPa for bulk samples.

PMID- 22588090
TI  - The search for ideal hernia repair; mesh materials and types.
AB  - Hernia surgery continues to draw the attention of surgeons, patients, and the
      industry. This strong interest has driven the establishment of professional
      medical societies with the sole purpose of furthering the understanding of
      hernias and hernia repair. In the more than 100 years of development, industry
      has played a major role in advancing the technology to perfect the performance of
      hernia repair with the hope of establishing the "best" technique and its
      associated technology. However, with the development of newer prosthetics and
      approaches to hernia repair, many surgeons do not fully understand the properties
      of the available prosthetics. The goal of this review is to highlight the
      different types of meshes in an effort to clarify to surgeons what types of
      materials are available to them and how to select an appropriate one for a given
      case.

PMID- 22588091
TI  - Correlative light and electron microscopy (CLEM) as a tool to visualize
      microinjected molecules and their eukaryotic sub-cellular targets.
AB  - The eukaryotic cell relies on complex, highly regulated, and functionally
      distinct membrane bound compartments that preserve a biochemical polarity
      necessary for proper cellular function. Understanding how the enzymes, proteins,
      and cytoskeletal components govern and maintain this biochemical segregation is
      therefore of paramount importance. The use of fluorescently tagged molecules to
      localize to and/or perturb subcellular compartments has yielded a wealth of
      knowledge and advanced our understanding of cellular regulation. Imaging
      techniques such as fluorescent and confocal microscopy make ascertaining the
      position of a fluorescently tagged small molecule relatively straightforward,
      however the resolution of very small structures is limited. On the other hand,
      electron microscopy has revealed details of subcellular morphology at very high
      resolution, but its static nature makes it difficult to measure highly dynamic
      processes with precision. Thus, the combination of light microscopy with electron
      microscopy of the same sample, termed Correlative Light and Electron Microscopy
      (CLEM), affords the dual advantages of ultrafast fluorescent imaging with the
      high-resolution of electron microscopy. This powerful technique has been
      implemented to study many aspects of cell biology. Since its inception, this
      procedure has increased our ability to distinguish subcellular architectures and
      morphologies at high resolution. Here, we present a streamlined method for
      performing rapid microinjection followed by CLEM (Fig. 1). The microinjection
      CLEM procedure can be used to introduce specific quantities of small molecules
      and/or proteins directly into the eukaryotic cell cytoplasm and study the effects
      from millimeter to multi-nanometer resolution (Fig. 2). The technique is based on
      microinjecting cells grown on laser etched glass gridded coverslips affixed to
      the bottom of live cell dishes and imaging with both confocal fluorescent and
      electron microscopy. Localization of the cell(s) of interest is facilitated by
      the grid pattern, which is easily transferred, along with the cells of interest,
      to the Epon resin used for immobilization of samples and sectioning prior to
      electron microscopy analysis (Fig. 3). Overlay of fluorescent and EM images
      allows the user to determine the subcellular localization as well as any
      morphological and/or ultrastructural changes induced by the microinjected
      molecule of interest (Fig. 4). This technique is amenable to time points ranging
      from <=5 s up to several hours, depending on the nature of the microinjected
      sample.

PMID- 22588092
TI  - A separation mechanism of photogenerated charges and magnetic properties for
      BiFeO3 microspheres synthesized by a facile hydrothermal method.
AB  - BiFeO(3) (BFO) microspheres were synthesized by a facile hydrothermal method. The
      optical absorption spectrum indicates that on site Fe(3+) crystal-field
      transitions and the charge transfer excitations can be observed. Magnetic
      measurements show a spin-glass behavior and room temperature weak ferromagnetism.
      The surface photovoltage spectroscopy of the BFO shows two response peaks
      centered at about 370 and 400 nm, respectively. Under an ambient atmosphere, the
      maximum surface photovoltage of the BFO reaches 180 MUV with the bias (+2 V) and
      is three times larger than that with zero bias. It is found that the surface
      photovoltage response intensity increases with an increase in applied bias,
      regardless of positive or negative bias. It is suggested that the surface
      photovoltaic properties are related to both the depolarization field owing to
      ferroelectric polarization and the build-in electric field due to the Schottky
      barrier. The micro-process and the physical mechanism of the separation of
      photogenerated charges for BFO are fully explained.

PMID- 22588093
TI  - Chitosan oligosaccharide-stabilized ferrimagnetic iron oxide nanocubes for
      magnetically modulated cancer hyperthermia.
AB  - Magnetic nanoparticles have gained significant attention as a therapeutic agent
      for cancer treatment. Herein, we developed chitosan oligosaccharide-stabilized
      ferrimagnetic iron oxide nanocubes (Chito-FIONs) as an effective heat
      nanomediator for cancer hyperthermia. Dynamic light scattering and transmission
      electron microscopic analyses revealed that Chito-FIONs were composed of multiple
      30-nm-sized FIONs encapsulated by a chitosan polymer shell. Multiple FIONs in an
      interior increased the total magnetic moments, which leads to localized
      accumulation under an applied magnetic field. Chito-FIONs also exhibited superior
      magnetic heating ability with a high specific loss power value (2614 W/g)
      compared with commercial superparamagnetic Feridex nanoparticles (83 W/g). The
      magnetically guided Chito-FIONs successfully eradicated target cancer cells
      through caspase-mediated apoptosis. Furthermore, Chito-FIONs showed excellent
      antitumor efficacy on an animal tumor model without any severe toxicity.

PMID- 22588096
TI  - Clavicle shaft fractures:  are children little adults?
AB  - Most clavicle shaft fractures in children are nondisplaced, minimally shortened
      or angulated, and are well treated with nonoperative management. Indications for
      operative fixation include open fractures and impending open fractures. Relative
      indications for operative fixation include fractures in multi-trauma patients,
      floating shoulder injuries, comminuted fractures, and shortened fractures in
      older adolescents. Controversies exist in preferred methods of fixation and
      include superior or anteroinferior plating, locked or unlocked plating, and
      intramedullary fixation. Retrospective studies of operative fixation in children
      show the feasibility and safety of fixation and are helping to define operative
      indications, but stronger evidence and reliable outcomes' measures for the
      pediatric upper extremity are still needed. Both nonoperative and operative
      treatment should be considered when making recommendations for treatment of
      significantly displaced or shortened midshaft clavicle fractures. The advantages
      and disadvantages of both should be clearly presented to the patient and family
      so that they may also participate in the decision-making process.

PMID- 22588097
TI  - Medial epicondyle fractures of the humerus:  how to evaluate and when to operate.
AB  - The fundamental principles of fracture care apply to medial epicondyle fractures
      in that the goals of treatment are to obtain fracture healing and to promote a
      return of appropriate motion, strength, and stability. Recent studies have
      revealed limitations of some classically described evaluation methods and have
      revealed more precise methods of measuring displacement. The authors of this
      manuscript describe established principles of care and incorporate recent
      evidence-based articles to help the clinician study the issues relative to the
      clinical evaluation and the operative and nonoperative treatment of medial
      epicondyle fractures.

PMID- 22588098
TI  - Pediatric radial neck fractures:  when and how to fix.
AB  - This is a review of current evaluation and treatment recommendations for
      pediatric radial neck fractures, including a series of cases that were presented
      and reviewed by a panel at The Pediatric Orthopedic Society of North America
      annual meeting 2010. We summarize the different published techniques for closed,
      percutaneous, and open reduction, and review when these techniques are
      recommended. The potential complications that can arise from radial neck
      fractures and their treatment are discussed.

PMID- 22588099
TI  - Forearm shaft fractures:  does fixation improve outcomes?

PMID- 22588100
TI  - Pediatric finger fractures:  which ones turn ugly?
AB  - The majority of pediatric finger fractures can be treated by closed means with
      expected excellent outcomes. However, a subset of fractures can turn "ugly," with
      complications such as growth arrest, malunion, and joint dysfunction if not
      recognized and treated appropriately. The present paper discusses several
      fractures in a child's fingers that can cause substantial problems if not
      recognized promptly, highlighting important themes in the evaluation and
      treatment of a child's injured finger.

PMID- 22588101
TI  - Flexibility in fixation:  an update on femur fractures in children.
AB  - Although non-operative strategies remain a viable option for the management of
      some children's femur fractures, surgical management has become more popular and
      predictable, with potential complications better recognized and thus more easily
      avoided. This paper addresses the operative management of children's femur
      fractures highlighting the multiple techniques available to treat the spectrum of
      pediatric femur fractures. We present the applications of Elastic Stable
      Intramedullary Nailing and Locked intramedullary nailing, sub-muscular or open
      plating, and external fixation, and discuss the relative advantages and
      shortcomings of each technique. Cases are presented for illustration.

PMID- 22588102
TI  - Growth plate fractures of the distal femur.
AB  - Growth plate fractures of the distal femur are challenging to treat, with
      complications that require a secondary surgery 40% to 60% of the time. These
      fractures often necessitate operative intervention, even in the youngest patients
      and even with minimal apparent displacement. Treatment varies with the Salter
      Harris (SH) classification and with the extent of initial displacement, ranging
      from simple casting for nondisplaced SH I fractures to open reduction and
      internal fixation for almost all SH III and IV fractures. Poor outcomes have been
      associated with pediatric fracture care of SH III and IV in 29% to 32% of cases.
      There are many pitfalls that have to be avoided in the treatment of these
      fractures to prevent malunion, growth arrest, and posttraumatic arthritis.

PMID- 22588103
TI  - Traumatic patellar dislocation: loose bodies and the MPFL.
AB  - Traumatic patellar dislocation is a common occurrence in adolescents. Treatment
      in the acute situation is controversial but should always address replacement or
      removal of osteochondral loose bodies. Reconstruction of the medial
      patellofemoral ligament in the acute and recurrent situation has provided
      excellent results in this select patient group.

PMID- 22588104
TI  - Lateral condylar humerus fractures:  which ones should we fix?
AB  - Lateral condyle fractures of the distal humerus are problematic whether displaced
      early or late. Operative intervention with closed reduction and percutaneous
      pinning or open reduction internal fixation are indicated for a malaligned
      articular surface and/or an unstable fracture. Intraoperative arthrograms can aid
      the surgeon in assessing joint reduction. LEVEL OF EVIDENCE: Case report.

PMID- 22588105
TI  - Tibia fractures: what should be fixed?
AB  - PURPOSE: The purpose of this study is to provide a summary of the absolute and
      the relative surgical indications for both closed and operative treatment of
      tibial shaft fractures. METHODS: A literature review of the pertinent literature
      was undertaken, and a limited number of the most significant papers are cited.
      Recommendations are provided for fractures that are most likely to need surgical
      intervention and relative indications for fractures that may benefit from
      surgical stabilization. RESULTS: Successful closed treatment can be achieved
      either by casting and conventional 3-point molding or by utilizing the Sarmiento
      technique of casting. Either technique depends on soft tissues to maintain bony
      alignment. The reported results are significantly improved after surgical
      stabilization after open tibial shaft fractures and tibial shaft fractures
      associated with ipsilateral femoral fractures. Relative indications for surgical
      stabilization include comminuted fractures, displaced fractures with an intact
      fibula, and displaced fractures in adolescents. Compartment syndrome remains the
      most significant early complication encountered when treating tibial shaft
      fractures in children and adolescents by either closed or surgical methods and
      should be considered in the face of pain out of proportion to the injury or
      increasing narcotic requirements. CONCLUSIONS: Tibial fractures are one of the
      more common injuries treated by orthopedic surgeons. Although most can be treated
      by closed techniques, certain fractures benefit significantly from surgical
      stabilization.

PMID- 22588106
TI  - Physeal fractures of the distal tibia and fibula (Salter-Harris Type I, II, III,
      and IV fractures).
AB  - Physeal fractures of the distal tibia and fibula are common and can be seen at
      any age, although most are seen in the adolescent. An understanding of the unique
      anatomy of the skeletally immature ankle in relation to the mechanism of injury
      will help one understand the injury patterns seen in this population. A thorough
      clinical exam is critical to the diagnosis and treatment of these injuries and
      the avoidance of potentially catastrophic complications. Nondisplaced physeal
      fractures of the distal tibia and fibula can be safely treated nonoperatively.
      Displaced fractures should undergo a gentle reduction with appropriate anesthesia
      while multiple reduction attempts should be avoided. Gapping of the physis >3 mm
      after reduction should raise the suspicion of entrapped periosteum that will
      increase the risk of premature physeal closure. Open reduction of displaced
      Salter-Harris type III and IV fractures is critical to maintain joint congruity
      and minimize the risk of physeal arrest.

PMID- 22588107
TI  - Triplane and Tillaux fractures: is a 2 mm residual gap acceptable?
AB  - Children's ankle fractures are the second most common growth plate fractures in
      humans and one of the top 10 reasons for pediatric orthopaedic hospital
      admissions. Because triplane and Tillaux fractures occur during the period of
      distal tibial physeal closure, they are considered transitional injuries. The
      distal tibial physis closes in a unique, asymmetric pattern (middle, then medial,
      and finally lateral), and it is the portion of the physis that is open at the
      time of injury that is vulnerable to fracture in this age group. Triplane and
      Tillaux fractures occur after supination external rotation and compression stress
      with unpredictable multiplanar fracture patterns. The fracture may appear
      different on different x-ray projections, making computed tomography mandatory to
      determine the number of fragments. Because most of these fractures are intra
      articular, anatomic or near-anatomic reduction of the joint surface is
      recommended to minimize future posttraumatic ankle arthritis. Because these
      fractures occur at the end of growth, they rarely result in growth arrest.

PMID- 22588108
TI  - Transient receptor potential ankyrin 1 ion channel contributes to guarding pain
      and mechanical hypersensitivity in a rat model of postoperative pain.
AB  - BACKGROUND: The transient receptor potential ankyrin 1 (TRPA1) ion channel is
      expressed on nociceptive primary afferent nerve fibers. On the distal ending, it
      is involved in transduction of noxious stimuli, and on the proximal ending
      (within the spinal dorsal horn), it regulates transmission of nociceptive
      signals. Here we studied whether the cutaneous or spinal TRPA1 ion channel
      contributes to mechanical hypersensitivity or guarding, an index of spontaneous
      pain, in an experimental model of postoperative pain in the rat. METHODS: A skin
      plus deep-tissue incision was performed under general anesthesia in the plantar
      skin of one hind paw, after which the incised skin was closed with sutures.
      Postoperative pain and hypersensitivity were assessed 24-48 h after the
      operation. Guarding pain was assessed by scoring the hind-paw position.
      Mechanical hypersensitivity was assessed with a calibrated series of
      monofilaments applied to the wound area in the operated paw or the contralateral
      control paw. Chembridge-5861528, a TRPA1 channel antagonist, was administered
      intaperitoneally (10-30 mg/kg), intraplantarly (10-30 MUg), or intrathecally (10
      MUg) in attempts to suppress guarding and hypersensitivity. RESULTS:
      Intraperitoneal or ipsi- but not contralateral intraplantar treatment with
      Chembridge-5861528 reduced mechanical hypersensitivity and guarding in the
      operated limb. Intrathecal treatment attenuated hypersensitivity but not
      guarding. Intraplantar Chembridge-5861528 suppressed preferentially mechanical
      hyperalgesia and intrathecal Chembridge-5861528 tactile allodynia. CONCLUSIONS:
      The TRPA1 channel in the skin contributes to sustained as well noxious mechanical
      stimulus-evoked postoperative pain, whereas the spinal TRPA1 channel contributes
      predominantly to innocuous mechanical stimulus-evoked postoperative pain.

PMID- 22588109
TI  - Battery ingestion resulting in an aortoesophageal fistula.

PMID- 22588110
TI  - Tumor growth inhibition by sonodynamic therapy using a novel sonosensitizer.
AB  - Sonodynamic therapy (SDT) with low-intensity ultrasound combined with a
      sonosensitizer may be a promising approach to cancer therapy. Use of ultrasound
      has the advantage of being noninvasive, with deep-penetration properties, and
      convenient because of the low or no sensitivity of sonosensitizers to light. In
      this study, SDT with a novel sonosensitizer (a porphyrin derivative) was
      evaluated in vitro and in vivo. Ultrasound irradiation with a sonosensitizer
      elicited potent sonotoxicity in vitro without the danger of phototoxicity. The
      sonotoxic effect was mediated by reactive oxygen species (ROS) and was reduced by
      ROS scavengers. Cell membrane lipid peroxidation increased significantly just
      after ultrasound irradiation with a sonosensitizer, but there was no increase in
      apoptosis. In an in vivo mouse xenograft model, SDT with a sonosensitizer
      markedly inhibited tumor cell growth. The skin hypersensitivity after light
      exposure was not observed in a sonosensitizer-treatment group, consistent with
      the in vitro findings. These results suggest that ROS generated by SDT with a
      sensitizer can damage tumor cells, resulting in necrosis and prevention of tumor
      growth. This noninvasive treatment with no adverse effects such as skin
      sensitivity is therefore promising for therapy of cancers located deep within
      patients.

PMID- 22588111
TI  - Perceived health status and environmental quality in the assessment of external
      costs of waste disposal facilities. An empirical investigation.
AB  - Taxation for urban waste management has been reformed in Italy by the
      introduction of an environmental law in 2006. In the planning phase of waste
      management, externalities generated by new facilities remain widely unaccounted,
      with a consequent distortion for prices, often raising local conflicts. The paper
      presents a survey based on the choice modelling methodology, aimed to evaluate on
      a monetary scale the disamenity effect perceived by incinerator and landfills in
      an Italian urban context: the city of Turin. In a random utility framework the
      behaviour of respondents, whose choices are found to be driven by the endowment
      of information about technological options, socio-economic characteristics as
      income, education, family composition, and also by their health status was
      modelled. Furthermore, empirical evidence that the behaviour in residential
      location choices is affected by different aspects of the respondent life and in
      particular by the health status was found. Distinct estimates of willingness to
      accept compensation for disamenity effects of incinerator (Euro 2670) and
      landfill (Euro 3816) are elicited. The effect of health status of the
      respondents, their level of information about the waste disposal infrastructure,
      the presence of a subjective strong aversion (NIMBY) and the actual endowment and
      concentration of infrastructures are demonstrated to be significant factors
      determining the choice behaviour, but differentiated and specific for
      incinerators and landfills.

PMID- 22588112
TI  - Evaluating greenhouse gas impacts of organic waste management options using life
      cycle assessment.
AB  - Efforts to divert organics away from landfills are viewed by many as an important
      measure to significantly reduce the climate change impacts of municipal solid
      waste management. However, the actual greenhouse gas (GHG) impacts of organics
      diversion from landfills have yet to be thoroughly evaluated and whether such a
      diversion provides significant environmental benefits in terms of GHG impacts
      must be answered. This study, using California-specific information, aimed to
      analyse the GHG impacts of organics diversion through a life-cycle assessment
      (LCA). This LCA considered all aspects of organics management including
      transportation, materials handling, GHG emissions, landfill gas
      capture/utilization, energy impacts, and carbon sequestration. The LCA study
      evaluated overall GHG impacts of landfilling, and alternative management options
      such as composting and anaerobic digestion for diverted organic waste. The LCA
      analysis resulted in net GHG reductions of 0.093, 0.048, 0.065 and 0.073 tonnes
      carbon equivalent per tonne organic waste for landfilling, windrow composting,
      aerated static pile composting, and anaerobic digestion, respectively. This study
      confirms that all three options for organics management result in net reductions
      of GHG emissions, but it also shows that organics landfilling, when well-managed,
      generates greater GHG reductions. The LCA provides scientific insight with
      regards to the environmental impacts of organics management options, which should
      be considered in decision and policy-making. The study also highlights the
      importance of how site and case-specific conditions influence project outcomes
      when considering organic waste management options.

PMID- 22588113
TI  - Methanogenic potential of formate in thermophilic anaerobic digestion.
AB  - In the present study the methanogenic potential of formate (HCOO(-)) during
      thermophilic anaerobic digestion was investigated. After appropriate conditions
      for methanogenesis (HCOO(-) and inoculum concentration, pH and duration of
      incubation) were assessed, an experiment with initial 31 replicates was run.
      Diluted fermenter sludge was used as inoculum, and process parameters including
      the pH, quality and quantity of the produced biogas and the concentrations of
      volatile fatty acids and HCO(3) (-) were determined. Remarkably, after 5 days of
      incubation the highest CH(4) production was calculated for a HCOO(-)
      concentration of 200 mmol L(-1), a concentration, however, which might not occur
      in situ. During the phase of high CH(4) production HCOO(-) was degraded with a
      rate of 1.5 mmol L(-1) h(-1), and distinct changes of Gibbs free energy for
      several reactions were observed. Based on denaturing high-performance liquid
      chromatography, denaturing gradient gel electrophoresis, and additional
      subsequent sequencing approaches the hydrogenotrophic Methanothermobacter wolfeii
      was the dominant methanogen responsible for CH(4) production. Further
      confirmation was achieved due to the detection of autofluorescing rods with a
      size of up to ~3 um, which were often arranged in pairs and chains. It was shown
      that even high concentrations of HCOO(-) are readily degraded, which might lead
      to an underestimation of both, the concentration and thus, the importance of
      HCOO(-) in anaerobic digestion.

PMID- 22588114
TI  - Detecting aircraft with a low-resolution infrared sensor.
AB  - Existing computer simulations of aircraft infrared signature (IRS) do not account
      for dispersion induced by uncertainty on input data, such as aircraft aspect
      angles and meteorological conditions. As a result, they are of little use to
      estimate the detection performance of IR optronic systems; in this case, the
      scenario encompasses a lot of possible situations that must be indeed addressed,
      but cannot be singly simulated. In this paper, we focus on low-resolution
      infrared sensors and we propose a methodological approach for predicting
      simulated IRS dispersion of poorly known aircraft and performing aircraft
      detection on the resulting set of low-resolution infrared images. It is based on
      a sensitivity analysis, which identifies inputs that have negligible influence on
      the computed IRS and can be set at a constant value, on a quasi-Monte Carlo
      survey of the code output dispersion, and on a new detection test taking
      advantage of level sets estimation. This method is illustrated in a typical
      scenario, i.e., a daylight air-to-ground full-frontal attack by a generic combat
      aircraft flying at low altitude, over a database of 90,000 simulated aircraft
      images. Assuming a white noise or a fractional Brownian background model,
      detection performances are very promising.

PMID- 22588116
TI  - The influence of filtering by the macular carotenoids on contrast sensitivity
      measured under simulated blue haze conditions.
AB  - PURPOSE: Distant objects are often obscured as a result of wavelength-dependent
      scattering in the atmosphere. This scattered light, which is mostly short-wave,
      effectively forms a veiling luminance (or background light) against which a
      target must be detected and discriminated. The macular pigment (MP) carotenoids
      could reduce the effective background intensity by selectively filtering out
      short wavelengths which would increase the contrast of the object in the retinal
      image, thus improving visibility. This Visibility hypothesis was originally
      posited by Wooten and Hammond (2002). This study represents a first empirical
      test of the hypothesis. METHODS: Five young healthy subjects were evaluated. MP
      optical density (OD) was measured using HFP. Visibility was assessed by measuring
      contrast sensitivity thresholds at 8 cycles/deg (CST) using an optical system
      that passed xenon-light through the sine-wave grating. Blue haze was simulated
      using an ecologically valid broad-spectrum filter. Changes in MP density were
      simulated using a variable path length filter with an oil-based carotenoid
      solution that mimicked the absolute absorption spectrum of MP. RESULTS: The
      average baseline CST was 0.004. Adding 0.25OD of simulated MP lowered the average
      threshold to 0.003 (25%). An additional 0.25OD decreased thresholds an additional
      10% and the effect reached a plateau at about 0.50. DISCUSSION: The largest
      improvement (about 25%) in contrast occurred with the initial, and relatively
      modest, addition of 0.25OD units of simulated MP suggesting that the largest
      improvements may be linked to initial increases in MPOD.

PMID- 22588117
TI  - Interocular transfer of spatial adaptation is weak at low spatial frequencies.
AB  - Adapting one eye to a high contrast grating reduces sensitivity to similar target
      gratings shown to the same eye, and also to those shown to the opposite eye.
      According to the textbook account, interocular transfer (IOT) of adaptation is
      around 60% of the within-eye effect. However, most previous studies on this were
      limited to using high spatial frequencies, sustained presentation, and criterion
      dependent methods for assessing threshold. Here, we measure IOT across a wide
      range of spatiotemporal frequencies, using a criterion-free 2AFC method. We find
      little or no IOT at low spatial frequencies, consistent with other recent
      observations. At higher spatial frequencies, IOT was present, but weaker than
      previously reported (around 35%, on average, at 8c/deg). Across all conditions,
      monocular adaptation raised thresholds by around a factor of 2, and observers
      showed normal binocular summation, demonstrating that they were not binocularly
      compromised. These findings prompt a reassessment of our understanding of the
      binocular architecture implied by interocular adaptation. In particular, the
      output of monocular channels may be available to perceptual decision making at
      low spatial frequencies.

PMID- 22588118
TI  - Drag in a resonantly driven polariton fluid.
AB  - We study the linear response of a coherently driven polariton fluid in the pump
      only configuration scattering against a point-like defect and evaluate
      analytically the drag force exerted by the fluid on the defect. When the system
      is excited near the bottom of the lower polariton dispersion, the sign of the
      interaction-renormalised pump detuning classifies the collective excitation
      spectra into three different categories (Ciuti and Carusotto 2005 Phys. Status
      Solidi b 242 2224): linear for zero, diffusive-like for positive and gapped for
      negative detuning. We show that both cases of zero and positive detuning share a
      qualitatively similar crossover of the drag force from the subsonic to the
      supersonic regime as a function of the fluid velocity, with a critical velocity
      given by the speed of sound found for the linear regime. In contrast, for gapped
      spectra, we find that the critical velocity exceeds the speed of sound. In all
      cases, the residual drag force in the subcritical regime depends on the polariton
      lifetime only. Also, well below the critical velocity, the drag force varies
      linearly with the polariton lifetime, in agreement with previous work
      (Cancellieri et al 2010 Phys. Rev. B 82 224512), where the drag was determined
      numerically for a finite-size defect.

PMID- 22588119
TI  - The identification of a new role for LEKTI in the skin: The use of protein 'bait'
      arrays to detect defective trafficking of dermcidin in the skin of patients with
      Netherton syndrome.
AB  - Lympho-Epithelial Kazal-Type-related Inhibitor (LEKTI) has been demonstrated to
      be an inhibitor of various kallikreins and is thought to play a role in the
      regulation of skin desquamation. In order to identify and investigate the
      potential of LEKTI to interact with other proteins, a method was developed using
      immobilised proteins onto arrays and nanoUPLC/MALDI-TOF MS. Using various domains
      of LEKTI, we demonstrated that these domains bound a number of kallikreins (5, 13
      and 14) to varied extents on the array surface. Inhibitory assays confirmed that
      binding on the protein array surface corresponded directly to levels of
      inhibition. The method was then tested using skin epidermal extracts. All forms
      of rLEKTI with the exception of rLEKTI 12-15, demonstrated the binding of several
      potential candidate proteins. Surprisingly, the major binding partners of LEKTI
      were found to be the antimicrobial peptide dermcidin and the serine protease
      cathepsin G and no kallikreins. Using confocal microscopy and Netherton syndrome
      skin sections, we confirmed the co-localisation of LEKTI with dermcidin and
      demonstrated altered trafficking of dermcidin in these patients. This potential
      new role for LEKTI as a multifunctional protein in the protection and transport
      of proteins in the epidermis and its role in disease are discussed.

PMID- 22588120
TI  - Protein S-nitrosylation and denitrosylation in the mouse spinal cord upon injury
      of the sciatic nerve.
AB  - Nitric oxide is a pain signaling molecule and exerts its influence through two
      primary pathways: by stimulation of soluble guanylylcyclase and by direct S
      nitrosylation (SNO) of target proteins. We assessed in the spinal cord the SNO
      proteome with two methods, two-dimensional S-nitrosothiol difference gel
      electrophoresis (2D SNO-DIGE) and SNO-site identification (SNOSID) at baseline
      and 24h after sciatic nerve injury with/without pretreatment with the nitric
      oxide synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME). After nerve
      injury, SNO-DIGE revealed 30 proteins with increased and 23 proteins with
      decreased S-nitrosylation. SNO-sites were identified for 17 proteins. After sham
      surgery only 3 proteins were up-nitrosylated. L-NAME pretreatment substantially
      reduced both constitutive and nerve injury evoked up-S-nitrosylation. For the top
      candidates S-nitrosylation was confirmed with the biotin switch technique and
      time course analyses at 1 and 7days showed that SNO modifications of protein
      disulfide isomerase, glutathione synthase and peroxiredoxin-6 had returned to
      baseline within 7days whereas S-nitrosylation of mitochondrial aconitase 2 was
      further increased. The identified SNO modified proteins are involved in
      mitochondrial function, protein folding and transport, synaptic signaling and
      redox control. The data show that nitric oxide mediated S-nitrosylation
      contributes to the nerve injury-evoked pathology in nociceptive signaling
      pathways.

PMID- 22588121
TI  - Batch effects correction improves the sensitivity of significance tests in
      spectral counting-based comparative discovery proteomics.
AB  - Shotgun proteomics has become the standard proteomics technique for the large
      scale measurement of protein abundances in biological samples. Despite
      quantitative proteomics has been usually performed using label-based approaches,
      label-free quantitation offers advantages related to the avoidance of labeling
      steps, no limitation in the number of samples to be compared, and the gain in
      protein detection sensitivity. However, since samples are analyzed separately,
      experimental design becomes critical. The exploration of spectral counting
      quantitation based on LC-MS presented here gathers experimental evidence of the
      influence of batch effects on comparative proteomics. The batch effects shown
      with spiking experiments clearly interfere with the biological signal. In order
      to minimize the interferences from batch effects, a statistical correction is
      proposed and implemented. Our results show that batch effects can be attenuated
      statistically when proper experimental design is used. Furthermore, the batch
      effect correction implemented leads to a substantial increase in the sensitivity
      of statistical tests. Finally, the applicability of our batch effects correction
      is shown on two different biomarker discovery projects involving cancer
      secretomes. We think that our findings will allow designing and executing better
      comparative proteomics projects and will help to avoid reaching false conclusions
      in the field of proteomics biomarker discovery.

PMID- 22588122
TI  - Assessing the impact of chloroacetanilide herbicides and their metabolites on
      periphyton in the Leyre River (SW France) via short term growth inhibition tests
      on autochthonous diatoms.
AB  - The Leyre River is the main tributary to the Bassin d'Arcachon lagoon. Herbicides
      belonging to the chloroacetanilide class have been found in the river (S
      metolachlor and acetochlor) as well as some of their metabolites at higher
      concentrations. As the environmental toxicity of these molecules is not well
      known, ecotoxicological tests have been carried out on river periphyton at
      different levels of biological diversity: from the clone of one diatom species
      (Nitzschia nana) to the population of the same species (several clones) up to the
      multi-specific species community dominated by diatoms. Moreover, tests were
      performed on diatoms coming from an unpolluted upstream site and from a
      contaminated downstream site, in order to investigate possible tolerance
      acquisition to pollutants. The method consisted in measuring diatom growth
      inhibition at different doses of each substance from the increase of chlorophyll
      a concentration after 4 days. It resulted that acetochlor was clearly more toxic
      than S-metolachlor at all levels of biological diversity. EC(50) values estimated
      from the tests suggest no effect of contaminants on diatom growth or biomass in
      the river. The toxicity of the metabolites appeared very low compared to that of
      their parent compounds. No difference in tolerance to the herbicides was
      demonstrated between summer diatom communities from the two sites in spite of
      different specific compositions. However, concerning the populations of N. nana
      isolated in winter following the highest herbicide concentrations in the river
      (about 0.5 MUg L(-1)), the downstream population showed a higher tolerance to
      acetochlor but there was no co-tolerance to S-metolachlor. Thus, it appeared that
      acetochlor represents the highest toxic pressure on periphyton among the other
      contaminants in the Leyre River.

PMID- 22588123
TI  - Assessment of cross-cultural adaptations and measurement properties of self
      report outcome measures relevant to shoulder disability in Portuguese: a
      systematic review.
AB  - OBJECTIVES: To evaluate the quality of the adaptation procedures as well as the
      clinimetric testing of the shoulder disability questionnaires available in
      Portuguese that has occurred for each adaptation. METHODS: Systematic literature
      searches on MEDLINE, EMBASE, CINAHL, SCIELO and LILACS were performed to identify
      relevant studies. Data on the quality of the cross-cultural adaptation procedures
      and clinimetric testing were extracted. All studies were evaluated according to
      the current guidelines for cross-cultural adaptation and measurement properties.
      RESULTS: Seven different questionnaires adapted into Brazilian-Portuguese (DASH,
      WORC, SPADI, PSS, ASORS, ASES and UCLA) were indentified from eleven studies.
      Most of the studies performed the cross-cultural adaptation procedures following
      the recommendations from the guidelines. From a total of seven instruments, two
      were not tested for any measurement property (PSS and ASES) and two
      questionnaires (DASH and WORC) were evaluated for almost all of properties. None
      of the questionnaires were fully tested for their measurement properties.
      CONCLUSIONS: Although most of the shoulder disability questionnaires have been
      properly adapted into Brazilian-Portuguese, some of them were either inadequately
      tested or not tested at all. It is recommended that only tested instruments can
      be used in clinical practice, as well as in research.

PMID- 22588124
TI  - A fully automated and highly versatile system for testing multi-cognitive
      functions and recording neuronal activities in rodents.
AB  - We have developed a fully automated system for operant behavior testing and
      neuronal activity recording by which multiple cognitive brain functions can be
      investigated in a single task sequence. The unique feature of this system is a
      custom-made, acoustically transparent chamber that eliminates many of the issues
      associated with auditory cue control in most commercially available chambers. The
      ease with which operant devices can be added or replaced makes this system quite
      versatile, allowing for the implementation of a variety of auditory, visual, and
      olfactory behavioral tasks. Automation of the system allows fine temporal (10 ms)
      control and precise time-stamping of each event in a predesigned behavioral
      sequence. When combined with a multi-channel electrophysiology recording system,
      multiple cognitive brain functions, such as motivation, attention, decision
      making, patience, and rewards, can be examined sequentially or independently.

PMID- 22588125
TI  - A novel calmodulin-beta-PIX interaction and its implication in receptor tyrosine
      kinase regulation.
AB  - Calmodulin (CaM), a ubiquitous calcium-binding protein, regulates numerous
      cellular processes, primarily in response to calcium flux. We have identified and
      characterized a novel interaction between CaM and beta-p21-activated kinase
      interacting exchange factor (beta-PIX), a putative guanine exchange factor
      implicated in cell signaling, using affinity pull-down assays, co
      immunoprecipitation, co-localization and circular dichroism studies. Fluorescence
      based titration and isothermal titration calorimetry experiments revealed a
      Ca(2+)-dependent binding mechanism (K(D)<=10MUM). Further, we show that CaM
      participates in a multi-protein complex involving beta-PIX and E3 ubiquitin
      ligase c-Cbl (casitas B-cell lymphoma), which may play a critical role in
      receptor tyrosine kinase regulation and downstream signaling.

PMID- 22588126
TI  - cAMP-elevation mediated by beta-adrenergic stimulation inhibits salt-inducible
      kinase (SIK) 3 activity in adipocytes.
AB  - Salt-inducible kinase (SIK) 3 is a virtually unstudied, ubiquitously expressed
      serine/threonine kinase, belonging to the AMP-activated protein kinase (AMPK)
      related family of kinases, all of which are regulated by LKB1 phosphorylation of
      a threonine residue in their activation (T)-loops. Findings in adrenal cells have
      revealed a role for cAMP in the regulation of SIK1, and recent findings suggest
      that insulin can regulate an SIK isoform in Drosophila. As cAMP has important
      functions in adipocytes, mainly in the regulation of lipolysis, we have evaluated
      a potential role for cAMP, as well as for insulin, in the regulation of SIK3 in
      these cells. We establish that raised cAMP levels in response to forskolin and
      the beta-adrenergic receptor agonist CL 316,243 induce a phosphorylation of SIK3
      in HEK293 cells and primary adipocytes. This phosphorylation coincides with
      increased 14-3-3 binding to SIK3 in these cell types. Our findings also show that
      cAMP-elevation results in reduced SIK3 activity in adipocytes. Phosphopeptide
      mapping and site-directed mutagenesis reveal that the cAMP-mediated regulation of
      SIK3 appears to depend on three residues, T469, S551 and S674, that all
      contribute to some extent to the cAMP-induced phosphorylation and 14-3-3-binding.
      As the cAMP-induced regulation can be reversed with the protein kinase A (PKA)
      inhibitor H89, and a role for other candidate kinases, including PKB and RSK,
      could be excluded, we believe that PKA is the kinase responsible for SIK3
      regulation in response to elevated cAMP levels. Our findings of cAMP-mediated
      regulation of SIK3 suggest that SIK3 may mediate some of the effects of this
      important second messenger in adipocytes.

PMID- 22588127
TI  - EGF-like peptide-enhanced cell movement in Dictyostelium is mediated by protein
      kinases and the activity of several cytoskeletal proteins.
AB  - DdEGFL1, a synthetic epidermal growth factor-like (EGFL) peptide based on the
      first EGFL repeat of the extracellular matrix, cysteine-rich, calmodulin-binding
      protein CyrA, has previously been shown to sustain the threonine phosphorylation
      of a 210kDa protein during the starvation of Dictyostelium cells.
      Immunoprecipitation coupled with a LC/MS/MS analysis identified the 210kDa
      protein as vinculin B (VinB). VinB shares sequence similarity with mammalian
      vinculin, a protein that links the actin cytoskeleton to the plasma membrane.
      Both threonine phosphorylated VinB (P-VinB) and VinB-GFP localized to the
      cytoplasm and cytoskeleton of Dictyostelium amoebae. VinB-GFP was also shown to
      be threonine phosphorylated and co-immunoprecipitated with established vinculin
      binding cytoskeletal proteins (e.g. myosin II heavy chain, actin, alpha-actinin,
      talin). P-VinB and VinB-GFP were detected in DdEGFL1 pull-down assays, which also
      identified a 135kDa phosphothreonine protein and two phosphotyrosine proteins (35
      and 32kDa) as potential components of the DdEGFL1 signaling pathway. DdEGFL1
      enhanced cell movement required the cytoskeletal proteins talin B and paxillin B
      and tyrosine kinase activity mediated by PKA signaling, however VinB threonine
      phosphorylation was shown to be independent of PI3K/PLA2 signaling and PI3K and
      PKA kinase activity. Finally, VinB-GFP over-expression suppressed DdEGFL1
      enhanced random cell movement, but not folic acid-mediated chemotaxis. Together,
      this study provides the first evidence for VinB function plus new insight into
      the signaling pathway(s) mediating EGFL repeat/peptide-enhanced cell movement in
      Dictyostelium. This information is integrated into an emerging model that
      summarizes existing knowledge.

PMID- 22588128
TI  - Variation in selective intensity over space alters classic mutation load
      predictions.

PMID- 22588129
TI  - Spatial heterogeneity in the strength of selection against deleterious alleles
      and the mutation load.
AB  - According to current estimates of genomic deleterious mutation rates (which are
      often of the order 0.1-1) the mutation load (defined as a reduction in the
      average fitness of a population due to the presence of deleterious alleles) may
      be important in many populations. In this paper, I use multilocus simulations to
      explore the effect of spatial heterogeneity in the strength of selection against
      deleterious alleles on the mutation load (for example, it has been suggested that
      stressful environments may increase the strength of selection). These simulations
      show contrasted results: in some situations, spatial heterogeneity may greatly
      reduce the mutation load, due to the fact that migrants coming from demes under
      stronger selection carry relatively few deleterious alleles, and benefit from a
      strong advantage within demes under weaker selection (where individuals carry
      many more deleterious alleles); in other situations, however, deleterious alleles
      accumulate within demes under stronger selection, due to migration pressure from
      demes under weaker selection, leading to fitness erosion within those demes. This
      second situation is more frequent when the productivity of the different demes is
      proportional to their mean fitness. The effect of spatial heterogeneity is
      greatly reduced, however, when the response to environmental differences is
      inconsistent across loci.

PMID- 22588130
TI  - A missense mutation in AGTPBP1 was identified in sheep with a lower motor neuron
      disease.
AB  - A type of lower motor neuron (LMN) disease inherited as autosomal recessive in
      Romney sheep was characterized with normal appearance at birth, but with
      progressive weakness and tetraparesis after the first week of life. Here, we
      carried out genome-wide homozygosity mapping using Illumina Ovine SNP50 BeadChips
      on lambs descended from one carrier ram, including 19 sheep diagnosed as affected
      and 11 of their parents that were therefore known carriers. A homozygous region
      of 136 consecutive single-nucleotide polymorphism (SNP) loci on chromosome 2 was
      common to all affected sheep and it was the basis for searching for the
      positional candidate genes. Other homozygous regions shared by all affected sheep
      spanned eight or fewer SNP loci. The 136-SNP region contained the sheep ATP/GTP
      binding protein 1 (AGTPBP1) gene. Mutations in this gene have been shown to be
      related to Purkinje cell degeneration (pcd) phenotypes including ataxia in mice.
      One missense mutation c.2909G>C on exon 21 of AGTPBP1 was discovered, which
      induces an Arg to Pro substitution (p.Arg970Pro) at amino-acid 970, a conserved
      residue for the catalytic activity of AGTPBP1. Genotyping of this mutation showed
      100% concordant rate with the recessive pattern of inheritance in affected,
      carrier, phenotypically normal and unrelated normal individuals. This is the
      first report showing a mutant AGTPBP1 is associated with a LMN disease in a large
      mammal animal model. Our finding raises the possibility of human patients with
      the same etiology caused by this gene or other genes in the same pathway of
      neuronal development.

PMID- 22588131
TI  - Genetic diversity and population structure in contemporary house sparrow
      populations along an urbanization gradient.
AB  - House sparrow (Passer domesticus) populations have suffered major declines in
      urban as well as rural areas, while remaining relatively stable in suburban ones.
      Yet, to date no exhaustive attempt has been made to examine how, and to what
      extent, spatial variation in population demography is reflected in genetic
      population structuring along contemporary urbanization gradients. Here we use
      putatively neutral microsatellite loci to study if and how genetic variation can
      be partitioned in a hierarchical way among different urbanization classes.
      Principal coordinate analyses did not support the hypothesis that urban/suburban
      and rural populations comprise two distinct genetic clusters. Comparison of FST
      values at different hierarchical scales revealed drift as an important force of
      population differentiation. Redundancy analyses revealed that genetic structure
      was strongly affected by both spatial variation and level of urbanization. The
      results shown here can be used as baseline information for future genetic
      monitoring programmes and provide additional insights into contemporary house
      sparrow dynamics along urbanization gradients.

PMID- 22588132
TI  - Effect of hydrogen-bonding on the excited-state reactivity of fullerene
      derivatives and its impact on the control of the emission polarisation from
      photopolic single crystals.
AB  - The kinetics of the irreversible photoinduced switch in polarisation (p) observed
      in single crystals of a fullerene derivative possessing hydrogen-bonding
      barbiturate units were investigated using confocal fluorescence microscopy. In
      the samples investigated, it was found that the maximum luminescence polarisation
      (p = 0.78) is obtained for an orientation of ca. 60 degrees  from the long axis
      of the crystal. Upon irradiation at 385 nm, the maximum luminescence polarisation
      undergoes a rotation of ca. 70 degrees  with respect to the initial orientation
      and reaches a new value of p = 0.40. The results indicate that the process is not
      dependent on the orientation of the incident polarised excitation beam and that
      it is not accompanied by a noticeable change in the photophysical properties of
      the crystal. Based on these observations, a mechanism is proposed in which
      photoinduced dimerisation occurs from the lowest energy emissive excimer-like
      state that acts as a sink for the excitation energy.

PMID- 22588134
TI  - Identification of a crab gill FXYD2 protein and regulation of crab microsomal
      Na,K-ATPase activity by mammalian FXYD2 peptide.
AB  - This investigation discloses the recognition of an FXYD2 protein in a microsomal
      Na,K-ATPase preparation from the posterior gills of the blue crab, Callinectes
      danae, by a mammalian (rabbit) FXYD2 peptide specific antibody (gammaC(33)) and
      MALDI-TOF-TOF mass spectrometry techniques. This is the first demonstration of an
      invertebrate FXYD2 protein. The addition of exogenous pig FXYD2 peptide to the
      crab gill microsomal fraction stimulated Na,K-ATPase activity in a dose-dependent
      manner. Exogenous pig FXYD2 also considerably increased enzyme affinity for K(+),
      ATP and NH(4)(+). K(0.5) for Na(+) was unaffected. Exogenous pig FXYD2 increased
      the V(max) for stimulation of gill Na,K-ATPase activity by Na(+), K(+) and ATP,
      by 30% to 40%. The crab gill FXYD2 is phosphorylated by PKA, suggesting a
      regulatory function similar to that known for the mammalian enzyme. The PKA
      phosphorylated pig FXYD2 peptide stimulated the crab gill Na,K-ATPase activity by
      80%, about 2-fold greater than did the non-phosphorylated peptide. Stimulation by
      the PKC-phosphorylated pig FXYD2 peptide was minimal. These findings confirm the
      presence of an FXYD2 peptide in the crab gill Na,K-ATPase and demonstrate that
      this peptide plays an important role in regulating enzyme activity.

PMID- 22588135
TI  - Extensive gluteal hematoma following InterStim implant: a case report.
AB  - Major bleeding complications following sacral nerve stimulation (SNS, InterStim)
      are exceptionally rare and have not been reported in the literature. We report a
      case of extensive gluteal hematoma following SNS procedure in a woman with a
      known history of thrombophilia.

PMID- 22588133
TI  - Effect of membrane tension on the physical properties of DOPC lipid bilayer
      membrane.
AB  - Molecular dynamics simulations of a dioleoylphosphocholine (DOPC) lipid bilayer
      were performed to explore its mechanosensitivity. Variations in the bilayer
      properties, such as area per lipid, volume, thickness, hydration depth (HD),
      hydration thickness (HT), lateral diffusion coefficient, and changes in lipid
      structural order were computed in the membrane tension range 0 to 15dyn/cm. We
      determined that an increase in membrane tension results in a decrease in the
      bilayer thickness and HD of ~5% and ~5.7% respectively, whereas area per lipid,
      volume, and HT/HD increased by 6.8%, 2.4%, and 5% respectively. The changes in
      lipid conformation and orientation were characterized using orientational (S(2))
      and deuterium (S(CD)) order parameters. Upon increase of membrane tension both
      order parameters indicated an increase in lipid disorder by 10-20%, mostly in the
      tail end region of the hydrophobic chains. The effect of membrane tension on
      lipid lateral diffusion in the DOPC bilayer was analyzed on three different time
      scales corresponding to inertial motion, anomalous diffusion and normal
      diffusion. The results showed that lateral diffusion of lipid molecules is
      anomalous in nature due to the non-exponential distribution of waiting times. The
      anomalous and normal diffusion coefficients increased by 20% and 52% when the
      membrane tension changed from 0 to 15dyn/cm, respectively. In conclusion, our
      studies showed that membrane tension causes relatively significant changes in the
      area per lipid, volume, polarity, membrane thickness, and fluidity of the
      membrane suggesting multiple mechanisms by which mechanical perturbation of the
      membrane could trigger mechanosensitive response in cells.

PMID- 22588136
TI  - Pregnancy and delivery after anterior vaginal mesh replacement: a case
      presentation.
AB  - A 36-year-old para 2 woman with Pelvic Organ Prolapse Quantification (POP-Q)
      stage III anterior prolapse and stress urinary incontinence (SUI) was treated
      using Polypropylene monofilament anterior vaginal mesh kit. She conceived 3
      months after mesh replacement. During pregnancy and after delivery, patient
      satisfaction was achieved in terms of symptom relief, and surgeon satisfaction
      was obtained in terms of anatomical results. Three years after cesarean section,
      she had no incontinence, and on exam, POP-Q score was Ba -2 cm. No mesh
      complication was noted, and no sexual dysfunction was declared. In summary,
      vaginal mesh kits can be used satisfactorily for patients with anterior prolapse
      and SUI who want to be pregnant.

PMID- 22588137
TI  - Sensory neuropathy following suspension of the vaginal apex to the proximal
      uterosacral ligaments.
AB  - INTRODUCTION AND HYPOTHESIS: Reports of sensory neuropathy attributed to
      uterosacral ligament suspension (USLS) have emerged. The objectives of this study
      were to assess the rate of sensory neuropathy symptoms following transvaginal
      USLS at a single institution during a 5-year period and to describe the
      evaluation, management, and outcomes in these patients. METHODS: A retrospective
      review of records identified 278 women who underwent transvaginal USLS during the
      study period. Inpatient and outpatient records within the first 4 weeks
      postsurgery were reviewed. Women with new-onset buttock and/or lower-extremity
      pain, numbness, weakness or a combination of these symptoms were identified.
      Demographic data, intraoperative data, and management modalities and outcomes
      were collected. RESULTS: Nineteen (6.8 %) women met criteria for inclusion. The
      most common symptom was buttock pain (73.7 % of cases). Pain radiation to the
      ipsilateral posterior thigh was present in 11 cases (57.9 %). The majority of
      women (73.7 %) reported pain symptoms on the right side. Conservative treatment
      modalities were initially implemented in all women. Four women (21 %) underwent
      suture removal a median of 1.75 months after USLS. Full symptom resolution was
      reported in 13 (68.4 %) women a median of 6 months after USLS. The remaining
      women experienced partial symptom resolution with ongoing conservative
      management. CONCLUSIONS: Sensory neuropathy is common in women who undergo
      transvaginal USLS. As quality of life may be significantly affected, any symptoms
      of buttock or lower-extremity pain in the immediate postoperative period warrant
      a thorough evaluation and close follow-up, with early suture removal
      consideration.

PMID- 22588138
TI  - Lower urinary tract symptoms in chronically constipated women.
AB  - INTRODUCTION AND HYPOTHESIS: The prevalence of lower urinary tract symptoms
      (LUTS) is as high as 66 % in the general population. Constipation rates of >30 %
      were reported among women with LUTS. We examined the association of chronic
      constipation to the occurrence of LUTS and, in particular, the relationship of
      LUTS to the type of constipation. We also examined the prevalence and association
      of pelvic organ prolapse (POP) to LUTS. METHODS: In a retrospective survey of
      data collected on patients referred to our clinic during 2008-2009 for assessment
      of chronic constipation, 161 constipated women and 162 healthy female volunteers
      completed a structured questionnaire of urinary and bowel habits components (BBUS
      Q22), the constipation scoring system for assessment of constipation severity and
      the Rome III component for IBS and chronic constipation. The constipated group
      underwent dynamic transperineal ultrasound. RESULTS: Demographic data was similar
      in both groups. LUTS were more common in the constipated group (increased urinary
      frequency 34 % vs. 14 %, p < 0.001, nocturia 31 % vs. 8 %, p < 0.001, urinary
      urgency 53 % vs. 21 %, p < 0.001, incomplete urinary emptying 24 % vs. 9 %, p =
      0.003 and urinary incontinence 21 % vs. 5 %, p < 0.0001). Urinary symptoms did
      not vary between IBS and functional constipation. In addition, the occurrence of
      urinary symptoms was unrelated to the diagnosis of posterior pelvic organ
      prolapse (POP) in the constipated group. CONCLUSIONS: LUTS are common in
      constipated women, but are unrelated to the type of constipation. These findings
      may suggest that the constipation process may have a direct contribution to the
      occurrence of LUTS.

PMID- 22588139
TI  - Transischioanal trans-sacrospinous ligament rectocele repair with polypropylene
      mesh: a prospective study with assessment of rectoanal function.
AB  - INTRODUCTION AND HYPOTHESIS: Despite good anatomical outcomes of pelvic organ
      prolapse (POP) repair by the vaginal route using synthetic mesh, complications
      limit their use. Clinical data are needed to generalize prolapse mesh repair by
      the vaginal route. The current study aims to evaluate midterm rectoanal function
      and clinical outcomes after transischioanal rectocele repair using a medium
      weight polypropylene mesh. METHODS: Between March 2003 and June 2004, 230
      patients with stage II-IV anterior and/or posterior POP were included in a
      prospective multicenter study. The current study is based on the analysis of the
      116 patients who underwent a rectocele repair via the infracoccygeal route
      through the sacrospinous ligament. Anatomical cure was defined when rectocele was
      at stage <II in the Pelvic Organ Prolapse Quantification (POP-Q) system.
      Postoperative functional results were evaluated using the self-administered
      Pelvic Floor Distress Inventory (PFDI) and the Pelvic Floor Impact Questionnaire
      (PFIQ). RESULTS: Of the 116 patients who received a posterior mesh with two arms
      via the infracoccygeal route through the sacrospinous ligament, midterm
      anatomical results were available for 78 women representing 67 % (78/116) of the
      operated patients. The mean follow-up was 36 (+/- 8.1) months. No rectal injury
      occurred during surgery. The objective success rate was 94.8 % and subjective (by
      patient satisfaction) was 93.23 %. Colorectal-Anal Impact (CRAI) and Colorectal
      Anal Distress Inventory (CRADI) scores were both significantly decreased at
      midterm follow-up in comparison with baseline (42.7 at baseline vs 11.4 at 24- or
      36-month follow-up, p = 0.001 for CRAI, and 81.1 vs 34.4, p < 0.001 for CRADI)
      highlighting the benefits of rectocele repair on colorectal-anal function.
      CONCLUSIONS: Polypropylene mesh with two arms via the infracoccygeal route
      through the sacrospinous ligament has good anatomical results at midterm follow
      up with significant improvement in symptoms and quality of life and is associated
      with few complications. Obstructive symptoms reported in cases of rectocele can
      be improved by transvaginal mesh repair.

PMID- 22588140
TI  - 75NC007 device for noninvasive stress urinary incontinence management in women: a
      randomized controlled trial.
AB  - INTRODUCTION AND HYPOTHESIS: Management of stress urinary incontinence (SUI) with
      intravaginal devices is an alternative to surgical management, but data of a high
      level of evidence remain scarce. Our goal was to assess efficacy, tolerance, and
      acceptability of the 75NC007 intravaginal device for SUI management. METHODS: A
      phase III, multicenter randomized controlled trial was conducted. After an
      initial washout period with no treatment, allowing baseline evaluation, women
      with SUI were randomly assigned to a treatment or control group (no treatment).
      The primary endpoint was the reduction of incontinence episode frequency (IEF),
      according to bladder diaries, as compared to baseline. Secondary endpoints were
      variation of the Urinary Symptom Profile (USP) score, of 24-h pad test, and of
      CONTILIFE questionnaire scores as compared to baseline. Intent-to-treat and per
      protocol analyses were conducted. RESULTS: Fifty-five patients were enrolled and
      analyzed (26 controls and 29 treated). The mean relative variations of IEF, SUI
      USP subscore, and overactive bladder (OAB) USP subscore were more significant in
      the treatment group than in the control group (-31.7 +/- 65.1 % vs -7.6 +/- 24.5
      %, p = 0.002, -2.4 +/- 2.6 vs 0.2 +/- 2.2, p = 0.004, and -1.5 +/- 2.8 vs 0.2 +/-
      1.8, p = 0.016, respectively). The dysuria USP subscore was slightly decreased in
      the treatment group. CONTILIFE scores were slightly improved in the treatment
      group. Pad test variations were not different between groups. No serious adverse
      event was noted throughout the entire study. CONCLUSIONS: The 75NC007
      intravaginal device is a safe and effective noninvasive treatment of SUI in
      women.

PMID- 22588141
TI  - Computed tomography-guided S3 lead placement for sacral neuromodulation.
AB  - Computed tomography (CT)-guided lead placement for sacral neuromodulation was
      used in a patient with arthritis and narrow S3 foramina. Bilateral S3 foramina
      were localized and guide needles were placed with CT guidance. Lead placement was
      further modified by placement of a tined, quadripolar lead through a dilated S3
      tract without initial somatosensory testing. The lead was then interrogated to
      assess placement and to differentiate superiority of response between two leads.
      The patient has had greater than 50 % improvement in urinary symptoms by voiding
      diary. Using CT guidance, satisfactory localization of bilateral S3 foramina may
      be achieved where prior attempts with conventional fluoroscopy have failed.

PMID- 22588142
TI  - Clinical and urodynamic differences among women with overactive bladder according
      to the presence of detrusor overactivity.
AB  - INTRODUCTION AND HYPOTHESIS: We tried to determine whether clinical and
      urodynamic differences exist between women with and without detrusor overactivity
      (DO) using a large database of overactive bladder (OAB) patients. METHODS: We
      reviewed the medical records of 513 women who underwent urodynamic studies for
      OAB symptoms without neurogenic or anatomical conditions that affect micturition
      function. Clinical symptoms were evaluated using a 3-day frequency-volume chart
      (FVC) including the Urinary Sensation Scale and American Urological Association
      Symptom Index (AUA-SI). All clinical and urodynamic findings were compared
      between women with and without DO. RESULTS: The patients' mean age was 58.9
      years. DO was identified urodynamically in 167 (32.6 %) women. Those with DO were
      older (62.9 vs 57.0 years, p < 0.001); however, no differences in AUA-SI,
      episodes of daytime voiding, and episodes of nocturia were observed between the
      groups. Functional bladder capacity was smaller in women with DO; however, this
      difference did not reach statistical significance. Women with DO had
      significantly more urgency incontinence symptoms than those without DO (55.1 vs
      29.5 %, p < 0.001). In urodynamic parameters, the volumes at first desire to void
      and strong desire to void and maximum cystometric capacity were significantly
      smaller, and detrusor pressure at the opening was significantly higher in women
      with DO compared to subjects without DO (26.2 vs 21.2 cmH(2)O, p = 0.004).
      CONCLUSIONS: Our findings suggest a more severe disturbance of bladder function
      when DO exists, although no differences were observed in symptom scores and 3-day
      FVC parameters among women with OAB symptoms according to the presence of DO.

PMID- 22588143
TI  - International Prostate Symptom Score for assessing lower urinary tract
      dysfunction in women.
AB  - INTRODUCTION AND HYPOTHESIS: Some lower urinary tract dysfunction (LUTD) subtypes
      may have similar symptoms. This study aimed to investigate the feasibility of
      using the International Prostate Symptom Score (IPSS) to evaluate lower urinary
      tract symptoms (LUTS) in women. METHODS: All consecutive women with non-stress
      urinary incontinence LUTS who visited the urologic clinics for treatment were
      prospectively enrolled. LUTS include urinary storage, voiding, and post
      micturition symptoms. All enrolled patients were requested to complete the
      Overactive Bladder Symptom Score (OABSS) and the modified Indevus Urgency
      Severity Scale (IUSS) questionnaires as well undergo uroflowmetry and post-void
      residual testing. A videourodynamic study was also performed, if indicated, for
      LUTD. RESULTS: A total of 222 women were enrolled, including 60 with overactive
      bladder (OAB) dry, 42 with OAB wet, 78 with bladder oversensitivity, and 42 with
      voiding dysfunction. A significantly higher IPSS voiding to storage subscore
      ratio (IPSS-V/S) and IPSS voiding score were found in the voiding dysfunction
      group. IPSS-V/S was found to have the highest area under the receiver-operating
      characteristic curve for predicting voiding LUTD than other noninvasive methods,
      and an IPSS-V/S of >=1.33 had the best predictive value for female voiding LUTD
      with a high negative predictive value (97.4 %). In addition, significantly higher
      IPSS storage subscore (IPSS-S) values were found in the OAB wet subgroup, and the
      IPSS-S was well correlated with the OABSS and IUSS. CONCLUSIONS: The IPSS can be
      used to evaluate female LUTD. IPSS-V/S may provide an initial guide for the
      treatment of voiding dysfunction in women. In addition, IPSS-S may be used for
      evaluating storage LUTD in women.

PMID- 22588144
TI  - Evaluation of a stochastic reconstruction algorithm for use in Compton camera
      imaging and beam range verification from secondary gamma emission during proton
      therapy.
AB  - In this paper, we study the feasibility of using the stochastic origin ensemble
      (SOE) algorithm for reconstructing images of secondary gammas emitted during
      proton radiotherapy from data measured with a three-stage Compton camera. The
      purpose of this study was to evaluate the quality of the images of the gamma rays
      emitted during proton irradiation produced using the SOE algorithm and to measure
      how well the images reproduce the distal falloff of the beam. For our evaluation,
      we performed a Monte Carlo simulation of an ideal three-stage Compton camera
      positioned above and orthogonal to a proton pencil beam irradiating a tissue
      phantom. Scattering of beam protons with nuclei in the phantom produces secondary
      gamma rays, which are detected by the Compton camera and used as input to the SOE
      algorithm. We studied the SOE reconstructed images as a function of the number of
      iterations, the voxel probability parameter, and the number of detected gammas
      used by the SOE algorithm. We quantitatively evaluated the capabilities of the
      SOE algorithm by calculating and comparing the normalized mean square error
      (NMSE) of SOE reconstructed images. We also studied the ability of the SOE
      reconstructed images to predict the distal falloff of the secondary gamma
      production in the irradiated tissue. Our results show that the images produced
      with the SOE algorithm converge in ~10,000 iterations, with little improvement to
      the image NMSE for iterations above this number. We found that the statistical
      noise of the images is inversely proportional to the ratio of the number of
      gammas detected to the SOE voxel probability parameter value. In our study, the
      SOE predicted distal falloff of the reconstructed images agrees with the Monte
      Carlo calculated distal falloff of the gamma emission profile in the phantom to
      within +/-0.6 mm for the positions of maximum emission (100%) and 90%, 50% and
      20% distal falloff of the gamma emission profile. We conclude that the SOE
      algorithm is an effective method for reconstructing images of a proton pencil
      beam from the data collected by an ideal Compton camera and that these images
      accurately model the distal falloff of secondary gamma emission during proton
      irradiation.

PMID- 22588145
TI  - Donor lungs with pulmonary embolism evaluated with ex vivo lung perfusion.
AB  - Acute pulmonary embolism (PE) compromises oxygenation and is typically considered
      a contraindication to lung donation for transplantation. We report the use of ex
      vivo lung perfusion (EVLP) to evaluate and possibly improve a pair of donor lungs
      with PE and poor oxygen exchange to a condition that might have been suitable for
      subsequent transplantation. A pair of donor lungs was procured for research after
      being declined for clinical use and placed on the EVLP circuit for 7 hours.
      Functional monitoring of the lungs revealed an increase in the partial pressure
      of oxygen to fraction of inspired oxygen ratio (P/F ratio) from 268 in situ to
      458 after EVLP. While on the circuit, pulmonary vascular resistance decreased as
      dynamic compliance of the lungs increased, suggesting they might have been
      acceptable for transplantation.

PMID- 22588146
TI  - In vitro performance testing of a pediatric oxygenator with an integrated
      pulsatile pump.
AB  - For different lung and heart diseases (e.g., acute respiratory distress syndrome,
      congenital heart failure, and cardiomyopathy) extracorporeal membrane oxygenation
      is a well-established therapy, particularly in the field of neonatal and
      pediatric medicine. To reduce the priming volume of the extracorporeal circuit,
      different components can be combined. In this study, an oval-shaped oxygenator
      (called ExMeTrA) with integrated pulsatile pump was tested in vitro using porcine
      blood. A feasibility study regarding the performance of collapsing and expanding
      silicone tubes within an oxygenator fiber bundle as a pulsatile pump was
      previously completed with successful results. The findings of this study improve
      upon the previous feasibility results, particularly in terms of gas exchange and
      filling volume. Five modules were manufactured in sizes of 20 +/- 2.2 ml (priming
      volume) with fiber surface areas of 0.24 +/- 0.027 m(2) and an analytically
      calculated volume pumping capacity of 692 +/- 75 ml/min. The modules were made of
      polymethylpentene fibers with dense outer layer to permit long-term applications.
      The gas exchange rates at a gas/blood flow ratio of 2:1 were between 64 and 72.7
      ml(O)(2)/l(blood) and between 62.5 and 81.5 ml/l(blood), depending on the blood
      flow. The individual module's pumping capacity ranged from 200-500 ml/min thus
      providing room for further improvements. In order to enhance the pumping capacity
      while maintaining sufficient gas exchange rates future optimization, adjustments
      will be made to the inlet and outlet geometries.

PMID- 22588147
TI  - A multicenter international survey of renal supportive therapy during ECMO: the
      Kidney Intervention During Extracorporeal Membrane Oxygenation (KIDMO) group.
AB  - Acute kidney injury and fluid overload (FO) are associated with increased
      mortality in critically ill patients, including the subset supported with
      extracorporeal membrane oxygenation (ECMO). The indication for and method of
      application of renal support therapy (RST) during ECMO is largely unknown beyond
      single-center experiences. The current study uses a survey design to document
      practice variation regarding RST, including indication, method of interface with
      the ECMO circuit, and prescribing practices. Sixty-five international ECMO
      centers (31%) responded to an online electronic survey regarding RST during ECMO.
      Nearly a quarter of centers (23%) reported using no RST during ECMO. Among those
      using the therapy, the predominant mode of therapy applied was convection and
      included slow continuous ultrafiltration and continuous venovenous
      hemofiltration. The predominant indication for RST was the treatment (43%) or
      prevention (16%) of FO. Nephrology rather than critical care medicine is reported
      as the prescribing service in a majority of centers with a significant difference
      between US centers and non-US centers. The results of this study identify a wide
      variation in practice regarding RST during ECMO that will offer multiple
      important avenues for further research by this group and others regarding the
      interface of RST and ECMO.

PMID- 22588148
TI  - Copper based metal-organic molecular ring with inserted Keggin-type
      polyoxometalate: a stable photofunctional host-guest molecular system.
AB  - Keggin polyphosphotungstate cluster was captured by a porous molecular ring with
      light sensitizing TPT molecules as connectors and copper ions as nodes. The self
      assembly reaction gives a stable host-guest supramolecular system, demonstrating
      efficient heterogeneous photocatalytic behavior for the degradation of methyl
      orange in near-neutral conditions.

PMID- 22588149
TI  - Use of longer periods of temporary detention to reduce mental health civil
      commitments.
AB  - OBJECTIVE: This study examined whether lengthening the holding period for an
      individual experiencing a mental health crisis under a temporary detention order
      (TDO) can reduce the number and length of post-TDO involuntary hospital
      commitments. METHODS: Data from the Virginia Court System were matched to the
      Commonwealth of Virginia Medicaid claims database for July 1, 2008, through March
      30, 2009. The final data set included 500 Medicaid recipients who had a mental
      health diagnosis and at least one TDO during the study period. Covariates
      included sex, race, age, primary diagnosis, and Community Service Board serving
      the individual. Logistic and multivariate regression models were used. RESULTS:
      Longer TDO periods were correlated with an increased probability of a dismissal
      of the commitment petition rather than hospitalization after a TDO. Among
      individuals who were hospitalized, longer TDO periods were correlated with an
      increased likelihood of voluntary hospitalization, rather than involuntary
      commitment, and shorter hospitalizations, although the net care time (TDO period
      plus post-TDO hospitalization) increased for individuals whose TDO length was
      greater than 24 hours. CONCLUSIONS: Longer TDO periods were correlated with
      shorter hospital stays and fewer involuntary commitments. These findings support
      previous work showing that short TDO periods provide insufficient time to
      stabilize and evaluate individuals. More research is needed to establish a causal
      link between TDO length and health outcomes.

PMID- 22588150
TI  - Polychlorinated biphenyls (PCBs) analysis using a miniaturized high-resolution
      time-of-flight mass spectrometer "MULTUM-S II".
AB  - In this study, we conducted polychlorinated biphenyls (PCBs) analysis using fast
      gas chromatography (GC)/high-resolution mass spectrometry (HRMS). Mass
      spectrometry (MS) was performed with a miniature multi-turn time-of-flight (TOF)
      analyzer called "MULTUM-S II". MULTUM-S II is truly a portable high resolution
      mass spectrometer. The mass spectrometer's high resolution capability is due to
      its theoretical infinite flight path utilizing perfect space and time focusing
      within a closed flight orbit. Mass resolution above 10 000 was easily achievable
      employing this portable system. This mass resolution is comparable to magnetic
      sector mass spectrometers, which have traditionally performed PCB analyses in the
      past. At a resolution of 10 000, a limit-of-detection of 1 ppb was determined
      using a heptachlorinated biphenyl standard sample. Using this fast GC/HRMS, 66
      PCB congeners were analyzed within 5 min. In addition experiments aimed at
      confirming interference of PCB signal peaks and matrix peaks in diluted
      dielectric coolant fluids were performed. We found that the PCB signal peaks were
      detected without matrix interference via high mass resolution.

PMID- 22588151
TI  - The mTOR pathway in lung cancer and implications for therapy and biomarker
      analysis.
AB  - Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that functions
      as a key regulatory protein in normal cell growth, survival, metabolism,
      development, and angiogenic pathways. Deregulation of these processes is a
      required hallmark of cancer, and dysregulation of mTOR signaling frequently
      occurs in a wide variety of malignancies, including lung cancer. Targeting of
      mTOR is thus an attractive strategy in the development of therapeutic agents
      against lung cancer. In this review, the mTOR-signaling pathway is described,
      highlighting opportunities for therapeutic intervention and biomarker analysis,
      and clinical trials in lung cancer including both non-small cell lung cancer and
      small cell lung cancer.

PMID- 22588152
TI  - A pooled exploratory analysis of the effect of tumor size and KRAS mutations on
      survival benefit from adjuvant platinum-based chemotherapy in node-negative non
      small cell lung cancer.
AB  - INTRODUCTION: The staging of node-negative non-small-cell lung cancer is modified
      in the 7th edition TNM classification. Here, we pool data from the National
      Cancer Institute of Canada Clinical Trials Group JBR.10 trial and the Cancer and
      Leukemia Group B-9633 trial to explore the prognostic and predictive effects of
      the new T-size descriptors and KRAS mutation status. METHODS: Node-negative
      patients were reclassified as T2a (>3-<=5 cm), T2b (>5-<=7 cm), T3 (>7 cm) or T
      <= 3 cm (<=3 cm, but other T2 characteristics). RESULTS: Of 538 eligible
      patients, 288 (53.5%) were T2a, 111 (21%) T2b, 62 (11.5%) T3, whereas 77 (14%)
      T<=3 cm were excluded to avoid confounding. KRAS mutations were detected in 104
      of 390 patients (27%). T-size was prognostic for disease-free survival (p =
      0.03), but borderline for overall survival (OS; p = 0.10), on multivariable
      analysis. Significant interaction between the prognostic value of KRAS and tumor
      size was observed for OS (p = 0.01), but not disease-free survival (p = 0.10).
      There was a nonsignificant trend (p = 0.24) for increased chemotherapy effect on
      OS with advancing T-size (hazard ratio [HR] T2a 0.90, [0.63-1.30]; T2b 0.69,
      [0.38-1.24]; and T3 0.57, [0.28-1.17]). The HR for chemotherapy effect on OS in
      T2a patients with KRAS wild-type tumors was 0.81 (p = 0.36), whereas a trend for
      detrimental effect was observed in those with mutant tumors (HR 2.11; p = 0.09;
      interaction p = 0.05). Similar trends were observed in T2b to T3 patients with
      wild-type (HR 0.86; p = 0.62), and KRAS mutant tumors (HR 1.16; p = 0.74;
      interaction p = 0.58). CONCLUSION: Chemotherapy effect seems to increase with
      tumor size. However, this small study could not identify subgroups of patients
      who did or did not derive significant benefit from adjuvant chemotherapy based on
      T-size or KRAS status.

PMID- 22588153
TI  - Early detection of lung cancer by molecular markers in endobronchial epithelial
      lining fluid.
AB  - INTRODUCTION: Early detection of malignancies in the lung by less-invasive
      methods aims at achieving efficient intervention and subsequently a reduction of
      the high mortality rate. We investigated whether biomarker analysis in
      endobronchial epithelial-lining fluid (ELF) collected by bronchoscopic
      microsampling (BMS) may be useful for a definitive preoperative diagnosis.
      METHODS: ELF was collected from subsegmental bronchi close to the indeterminate
      pulmonary nodule, which was detected by computed tomography, and from the
      contralateral lung. Diagnosis was confirmed by transbronchial biopsy or surgery.
      The study includes 142 ELF samples from 51 non-small-cell lung cancer patients
      and 20 benign cases. Microarray analysis was done with a patient subset (n = 15)
      to narrow down genes associated with a malignant phenotype. Thirteen potential
      biomarkers have been further analyzed by quantitative real-time polymerases chain
      reaction in an independent patient cohort (n = 56). RESULTS: All patients
      underwent BMS without complications. Gene-expression analyses by microarrays and
      quantitative real-time polymerases chain reaction could be reliably applied to
      ELF samples, and resulted in potential biomarkers for malignant pulmonary
      nodules. Four genes (tenascin-C, [C-X-C motif] ligand 14, S100 calcium binding
      protein A9, and keratin 17) were found to be upregulated in ELF of non-small-cell
      lung cancer patients with adenocarcinoma or squamous cell carcinoma. Combined
      analysis of tenascin-C expression and the nodule size improved the prediction of
      malignancy in this patient cohort. CONCLUSIONS: Our study suggests that the
      analysis of specific biomarkers in ELF collected by BMS could be a potentially
      useful adjunct to other diagnostic techniques aiming at the preoperative
      diagnosis of malignant pulmonary nodules.

PMID- 22588154
TI  - Lung cancer screening and video-assisted thoracic surgery.
AB  - INTRODUCTION: The objective of this study is to report the impact of computed
      tomography (CT) screening on the use of Video-Assisted Thoracic Surgery (VATS) in
      a randomized screening trial. METHODS: The Danish Lung Cancer Screening Trial is
      a randomized clinically controlled trial of 4104 smokers and previous smokers who
      were randomized to either screening with five annual low-dose CT scans or no
      screening in Copenhagen from 2004 to 2006. The major end point is the effect of
      CT screening on lung cancer mortality and treatment options. All diagnostic and
      treatment interventions in both groups were monitored prospectively until 1 to 3
      years after the last screening round. RESULTS: By February 1, 2011 68 cases of
      lung cancer were detected in the screening group. Furthermore, seven patients
      with a benign nodule underwent surgical treatment because of suspicion of
      malignancy (12%). Fifty-one of the 68 lung cancer patients were eligible for
      surgical treatment. Eight patients had open thoracotomy. Of the operations for
      lung cancer, 84% were performed by VATS in the CT-screened arm, significantly
      higher than the control arm (p < 0.05). Thirty-six patients had a VATS lobectomy.
      One patient had a VATS segmentectomy, and four patients had a VATS wedge
      resection. The seven benign nodules were all treated with VATS. CONCLUSIONS: CT
      screening seems to facilitate the use of VATS in the treatment of lung cancer
      with an 84% rate in our data. Furthermore, all benign nodules could be removed by
      VATS. In our view, a basic requirement for a surgical institution to be involved
      in lung cancer CT screening is a dedicated VATS program.

PMID- 22588155
TI  - Screening for germline EGFR T790M mutations through lung cancer genotyping.
AB  - INTRODUCTION: The study of patients carrying germline epidermal [corrected]
      growth factor receptor (EGFR) mutations, which have been found in cases of
      familial lung adenocarcinoma, could provide unique insight into lung cancer risk
      and carcinogenesis in never-smokers. However, investigations into the biology of
      germline EGFR mutations have been hampered by the lack of an effective strategy
      for screening for carriers. We hypothesized that patients with lung cancers found
      to harbor the EGFR T790M resistance mutation before treatment, an uncommon
      occurrence, would be likely to carry underlying germline T790M mutations.
      METHODS: Eleven unrelated patients with lung cancer, harboring an EGFR T790M
      mutation, were identified from a 7-year institutional experience with tumor
      genotyping. Ten patients had benign tissue available, which was anonymously
      tested for the presence of germline EGFR mutations. RESULTS: Five of 10 cases
      carried a germline T790M mutation (50%, confidence interval 27%-73%). One
      patient's cancer exhibited a distinctive indolent growth, which has also been
      described in preclinical studies of T790M-mutant cancers. A second patient
      underwent resection of six separate primary lung adenocarcinomas, each carrying
      different sensitizing EGFR mutations and T790M. CONCLUSIONS: Genotyping of lung
      cancers, now commonly performed to predict benefit from treatment with EGFR
      tyrosine kinase inhibitors, can also be used as a screening tool to identify
      patients at risk of carrying germline EGFR mutations. Once identified, these
      patients and their families can be studied prospectively to explore appropriate
      lung cancer screening strategies. Further studies using existing oncogenomic data
      to provide insight into underlying germline genetics are warranted.

PMID- 22588156
TI  - Tasisulam sodium (LY573636 sodium) as third-line treatment in patients with
      unresectable, metastatic non-small-cell lung cancer: a phase-II study.
AB  - INTRODUCTION: Tasisulam sodium (hereafter referred to as tasisulam) is a novel
      anticancer compound that induces apoptosis and exhibits antiangiogenesis activity
      in a broad range of cancer models, including non-small-cell lung cancer (NSCLC).
      METHODS: Tasisulam was administered as a 2-hour infusion every 21 days as third
      line treatment in patients with advanced (stage IIIB/IV) NSCLC. RESULTS: Thirty
      two patients received a Cmax target dose of 420 ug/ml. Median time to progression
      was 3.12 months, median progression-free survival was 2.69 months, and median
      overall survival was 8.48 months. There were no objective responses; 43.8% of
      patients achieved stable disease. A high rate of grade-4 hematologic toxicity in
      the first 30 patients led to exploration of a lower Cmax target dose of 380
      ug/ml. The rate of grade-4 hematologic toxicity (thrombocytopenia and/or
      neutropenia) at the 380-ug/ml dose (n = 20) was 20% versus 34% at the 420-ug/ml
      dose. CONCLUSIONS: Tasisulam has only modest activity as a third-line treatment
      of patients with unresectable/metastatic NSCLC. The high rate of grade-4
      hematologic toxicity observed with this highly albumin- bound compound in this
      patient population provided challenges for fixed Cmax-based dosing. Alternative
      dosing methods, including varying the Cmax target dose by predose albumin, are
      under investigation in other studies.

PMID- 22588157
TI  - Tubular tumor growth along entire biopsy track of brain metastasis.

PMID- 22588158
TI  - Erlotinib in symptomatic brain metastases from a lung adenocarcinoma with a
      sensitizing EGFR mutation.

PMID- 22588159
TI  - Secondary resistance to erlotinib: acquired T790M mutation and small-cell lung
      cancer transformation in the same patient.

PMID- 22588160
TI  - Same dataset, same conclusion, different in detail: who's doing what from large
      public database?

PMID- 22588162
TI  - Effect of sample dilution on two free light chain nephelometric assays.

PMID- 22588161
TI  - The influence of acute, late-life calorie restriction on whole body energy
      metabolism in p66Shc(-/-) mice.
AB  - It has been proposed that Shc proteins may influence aging by regulating insulin
      signaling and energy metabolism. Evidence suggests that deletion of p66Shc could
      partially attenuate weight gain on a high fat diet by increasing energy
      expenditure. However, the impact of p66Shc on the metabolic response to calorie
      restriction (CR) has not been determined. Thus, we used indirect respiration
      calorimetry to determine the impact of CR on energy expenditure (EE) and
      substrate utilization (RQ) in 18mo p66Shc(-/-) and wild-type (WT) mice.
      Calorimetry measurements were completed at baseline and following 3d of 40% CR
      and 2 mo of 26% CR. There was no difference (P>0.10) in EE and RQ between
      gentoypes, regardless of how EE data was normalized. Both p66Shc(-/-) and WT mice
      showed decreases (P<0.001) in EE normalized for body weight at 2 mo of CR.
      However, the response to 3d of CR was different between genotypes with only the
      p66Shc(-/-) showing a decrease (P<0.001) in 24 h EE expressed per mouse or
      normalized for body weight. The results indicate that p66Shc does not
      significantly influence EE in 18 mo mice at baseline or 2 mo of CR, although it
      may play a role in the EE response to very acute CR.

PMID- 22588163
TI  - Novel mutations of CYP27B1 gene lead to reduced activity of 1alpha-hydroxylase in
      Chinese patients.
AB  - Pseudovitamin D-deficiency rickets (PDDR) is an autosomal recessive disorder
      resulting from a defect in renal 25-hydroxyvitamin D 1alpha-hydroxylase, the key
      enzyme in the pathway of vitamin D metabolism. We identified ten different
      mutations in the 1alpha-hydroxylase gene (CYP27B1) in eight Chinese families with
      PDDR by DNA-sequence analysis. Six of them are novel missense mutations: G57V,
      G73W, L333F, R432C, R459C, and R492W; three are novel deletion mutations: c48
      60del, c1310delG, and c1446delA; and an insertion mutation c1325-1332insCCCACCC
      reported previously. Functional assay revealed that the missense mutants
      identified in this study retain 5.5-12.1% 1alpha-hydroxylase activity of the wild
      type. The study describes nine novel mutations in addition to 37 known mutations
      of CYP27B1 gene and shows the correlation between these mutations and the
      clinical findings of 1alpha-hydroxylase deficiency.

PMID- 22588164
TI  - Progressive-ratio responding for palatable high-fat and high-sugar food in mice.
AB  - Foods that are rich in fat and sugar significantly contribute to over-eating and
      escalating rates of obesity. The consumption of palatable foods can produce a
      rewarding effect that strengthens action-outcome associations and reinforces
      future behavior directed at obtaining these foods. Increasing evidence that the
      rewarding effects of energy-dense foods play a profound role in overeating and
      the development of obesity has heightened interest in studying the genes,
      molecules and neural circuitry that modulate food reward. The rewarding impact of
      different stimuli can be studied by measuring the willingness to work to obtain
      them, such as in operant conditioning tasks. Operant models of food reward
      measure acquired and voluntary behavioral responses that are directed at
      obtaining food. A commonly used measure of reward strength is an operant
      procedure known as the progressive ratio (PR) schedule of reinforcement. In the
      PR task, the subject is required to make an increasing number of operant
      responses for each successive reward. The pioneering study of Hodos (1961)
      demonstrated that the number of responses made to obtain the last reward, termed
      the breakpoint, serves as an index of reward strength. While operant procedures
      that measure changes in response rate alone cannot separate changes in reward
      strength from alterations in performance capacity, the breakpoint derived from
      the PR schedule is a well-validated measure of the rewarding effects of food. The
      PR task has been used extensively to assess the rewarding impact of drugs of
      abuse and food in rats (e.g., 6-8), but to a lesser extent in mice. The increased
      use of genetically engineered mice and diet-induced obese mouse models has
      heightened demands for behavioral measures of food reward in mice. In the present
      article we detail the materials and procedures used to train mice to respond
      (lever-press) for a high-fat and high-sugar food pellets on a PR schedule of
      reinforcement. We show that breakpoint response thresholds increase following
      acute food deprivation and decrease with peripheral administration of the
      anorectic hormone leptin and thereby validate the use of this food-operant
      paradigm in mice.

PMID- 22588165
TI  - Fast range-corrected proton dose approximation method using prior dose
      distribution.
AB  - For robust plan optimization and evaluation purposes, one needs a computationally
      efficient way to calculate dose distributions and dose-volume histograms (DVHs)
      under various changes in the variables associated with beam delivery and images.
      In this study, we report an approximate method for rapid calculation of dose when
      setup errors and anatomical changes occur during proton therapy. This fast dose
      approximation method calculates new dose distributions under various
      circumstances based on the prior knowledge of dose distribution from a reference
      setting. In order to validate the method, we calculated and compared the dose
      distributions from our approximation method to the dose distributions calculated
      from a clinically commissioned treatment planning system which was used as the
      ground truth. The overall accuracy of the proposed method was tested against
      varying degrees of setup error and anatomical deformation for selected patient
      cases. The setup error was simulated by rigid shifts of the patient; while the
      anatomical deformation was introduced using weekly acquired repeat CT data sets.
      We evaluated the agreement between the dose approximation method and full dose
      recalculation using a 3D gamma index and the root-mean-square (RMS) and maximum
      deviation of the cumulative dose volume histograms (cDVHs). The average passing
      rate of 3D gamma analysis under 3% dose and 3 mm distance-to-agreement criteria
      were 96% and 89% for setup errors and severe anatomy changes, respectively. The
      average of RMS and maximum deviation of the cDVHs under the setup error was 0.5%
      and 1.5%, respectively for all structures considered. Similarly, the average of
      RMS and maximum deviations under the weekly anatomical change were 0.6% and 2.7%,
      respectively. Our results show that the fast dose approximation method was able
      to account for the density variation of the patient due to the setup and
      anatomical changes with acceptable accuracy while significantly improving the
      computation time.

PMID- 22588166
TI  - AMPK activators inhibit the proliferation of human melanomas bearing the
      activated MAPK pathway.
AB  - Raf/MEK/ERK signaling can inhibit the liver kinase B1-AMP-activated protein
      kinase (LKB1-AMPK) pathway, thus rendering melanoma cells resistant to energy
      stress conditions. We evaluated whether pharmacological reactivation of the AMPK
      function could exert antitumor effects on melanoma cells bearing this pathway
      constitutively active because of a mutation in NRAS or BRAF genes. Nine melanoma
      cell lines were treated with the AMPK activators 5-aminoimidazole-4-carboxamide
      ribonucleoside (AICAR) and phenformin. The activation of AMPK enzymatic activity,
      phosphorylation of AMPK and acetyl-CoA carboxylase kinase, in-vitro
      proliferation, cell cycle, and in-vivo growth of xenografts in nude mice were
      evaluated. AICAR and phenformin promoted phosphorylation and enzymatic activity
      of AMPK, as well as phosphorylation of the AMPK downstream target acetyl-CoA
      carboxylase. Drug treatment of either BRAF-mutant or NRAS-mutant melanomas, at
      doses not inducing cell death, was accompanied by a dose-dependent decrease in
      melanoma cell proliferation because of cell cycle arrest in either the G0/G1 or
      the S phase, associated with an increased expression of the p21 cell cycle
      inhibitor. Melanomas isolated from subcutaneously implanted mice, 25 days from
      treatment with AICAR, showed increased staining of the senescence-associated
      marker beta-galactosidase, high p21 expression, and evidence of necrosis.
      Altogether, these results indicate that pharmacological activators of AMPK
      dependent pathways inhibit the cell growth of melanoma cells with active
      Raf/MEK/ERK signaling and provide a rationale for further investigation on their
      use in combination therapies.

PMID- 22588167
TI  - An examination of costs, charges, and payments for inpatient psychiatric
      treatment in community hospitals.
AB  - OBJECTIVE: Hospitalization is a critical component of treatment for individuals
      with serious and persistent mental illness. Despite its resource intensity, the
      costs of inpatient psychiatric hospitalizations in the United States are not well
      understood. The objective of this research was to provide cost estimates for
      inpatient psychiatric care. METHODS: Using Premier's Perspective Comparative
      Database, supplemented with the MarketScan database, this study estimated the
      average charges, cost to provide care, and amount of reimbursement for inpatient
      psychiatric care in 418 community-based hospitals in 2006 (N=261,996
      hospitalizations). RESULTS: Charges were 2.5 times higher than the hospitals'
      reported costs to deliver care. Reimbursed amounts indicated by MarketScan were
      similar to the reported costs to deliver care. The average cost to deliver care
      was highest for Medicare and lowest for the uninsured: schizophrenia treatment,
      $8,509 for 11.1 days and $5,707 for 7.4 days, respectively; bipolar disorder
      treatment, $7,593 for 9.4 days and $4,356 for 5.5 days; depression treatment,
      $6,990 for 8.4 days and $3,616 for 4.4 days; drug use disorder treatment, $4,591
      for 5.2 days and $3,422 for 3.7 days; and alcohol use disorder treatment, $5,908
      for 6.2 days and $4,147 for 3.8 days. CONCLUSIONS: Consistent with past research,
      the results suggest that previous attempts to control pricing may have led to
      unintended consequences, including a large gap between charges and reimbursed
      amounts, potential cost shifting between payers, and potentially extended lengths
      of stay to offset reduced per diems. The lack of transparency in pricing makes it
      challenging to estimate the cost to society for a day of psychiatric
      hospitalization.

PMID- 22588168
TI  - Nursing informatics education past, present, and future.

PMID- 22588169
TI  - From passion to excellence: national nursing informatics movement in Taiwan.

PMID- 22588171
TI  - Infrared spectra of ethylene clusters: (C2D4)2 and (C2D4)3.
AB  - Spectra of ethylene dimers and trimers are studied in the nu(11) fundamental band
      region of C(2)D(4) (~2200 cm(-1)) using a tuneable quantum cascade laser to probe
      a pulsed supersonic slit jet expansion. The dimer spectrum is that of a prolate
      symmetric top perpendicular band, with a distinctive appearance because the A
      rotational constant is almost exactly equal to six times the B constant. The
      analysis supports the previously determined cross-shaped dimer structure with
      D(2d) symmetry. An ethylene trimer has not previously been observed with
      rotational resolution. The spectrum is that of an oblate symmetric top parallel
      band. It leads to a proposed trimer structure which is barrel shaped and has
      C(3h) or C(3) symmetry, with the ethylene monomer C-C axes approximately aligned
      along the trimer symmetry axis.

PMID- 22588172
TI  - Disease-drug pairs revealed by computational genomic connectivity mapping on GBA1
      deficient, Gaucher disease mice.
AB  - We have reported that, in addition to recapitulating the classical human Gaucher
      disease (GD1) phenotype, deletion of the glucocerebrosidase (GBA1) gene in mice
      results in the dysfunction of a diverse population of immune cells. Most of
      immune-related, non-classical features of GD1, including gammopathies and
      autoimmune diathesis, are resistant to macrophage-directed therapies. This has
      prompted a search for newer agents for human GD1. Here, we used high-density
      microarray on splenic and liver cells from affected GBA1(-/-) mice to establish a
      gene "signature", which was then utilized to interrogate the Broad Institute
      database, CMAP. Computational connectivity mapping of disease and drug pairs
      through CMAP revealed several highly enriched, non-null, mimic and anti-mimic
      hits. Most notably, two compounds with anti-helminthic properties, namely
      albendazole and oxamniquine, were identified; these are particularly relevant for
      future testing as the expression of chitinases is enhanced in GD1.

PMID- 22588173
TI  - Differential expression of secreted phosphoprotein 1 in response to estradiol
      17beta and in ovarian tumors in chickens.
AB  - Secreted phosphoprotein 1 (SPP1), a highly phosphorylated protein containing a
      polyaspartic acid sequence and a conserved RGD motif, plays important roles in
      physiological processes such as inflammatory responses, calcification, organ
      development, immune cell function and carcinogenesis. Results of the present
      study indicate expression of SPP1 mRNA in various organs such as oviduct, small
      intestine and kidney from chickens, particularly in the glandular epithelium (GE)
      of the shell gland and, to a lesser extent, in luminal epithelium (LE) of the
      infundibulum and magnum, and GE of the isthmus of the oviduct. We determined that
      DES (diethylstilbestrol, a synthetic nonsteroidal estrogen) decreases SPP1
      expression in the oviduct and that SPP1 mRNA and protein are significantly more
      abundant in GE of ovarian endometrioid carcinoma, but not the other cancerous and
      normal ovaries of hens. Further, microRNA-140 was discovered to influence SPP1
      expression via its 3'-UTR which suggests that post-transcriptional regulation
      influences SPP1 expression in chickens. Collectively, results of this study
      indicate that SPP1 is novel in that its expression is down-regulated by estrogen
      in epithelial cells of the chicken oviduct and that it is up-regulated in chicken
      ovarian endometrioid tumor that could be used for monitoring effects of therapies
      for this disease in laying hens.

PMID- 22588174
TI  - TRIM59 interacts with ECSIT and negatively regulates NF-kappaB and IRF-3/7
      mediated signal pathways.
AB  - Innate immune responses are triggered by pathogen-associated molecular patterns
      (PAMPs) through pattern recognition receptors (PRRs) and then activate
      intracellular signaling pathways including NF-kappaB and interferon regulatory
      factors. Recently, it has been reported that tripartite motif (TRIM) proteins
      function as crucial regulators via ubiquitin-mediated modifications for these
      signaling pathways. In this study, we showed that one of the TRIM family
      ubiquitin ligases, TRIM59, interacts with ECSIT as an adaptor protein required
      for the TLR-mediated transduction pathway. Luciferase reporter assays using
      reporter plasmids including NF-kappaB responsive element, interferon beta (IFN
      beta) promoter and interferon-sensitive response element (ISRE) showed that
      overexpression of TRIM59 repressed their transcriptional activities, whereas
      knockdown of TRIM59 enhanced their transcriptional activities. Furthermore,
      TRIM59 inhibited phosphorylation and dimerization of IRF3 and IRF7, suggesting
      that TRIM59 negatively regulates upstream kinases for IRFs. These findings
      indicate that TRIM59 may serve as a multifunctional regulator for innate immune
      signaling pathways.

PMID- 22588175
TI  - Antibacterial activity of class IIa bacteriocin Cbn BM1 depends on the
      physiological state of the target bacteria.
AB  - Carnobacteriocin BM1 (Cbn BM1) is a class IIa bacteriocin produced by
      Carnobacterium maltaromaticum CP5 isolated from a French mold ripened cheese.
      Numerous studies highlight variations in numerous parameters, such as bacterial
      membrane composition and potential, according to physiological changes. In this
      work, the mechanism of action of an oxidized form of Cbn BM1 was studied on C.
      maltaromaticum DSM20730 in log and stationary growth phases. Membrane integrity
      assessment and high resolution imaging by atomic force microscopy confirmed the
      link between physiological state and bacterial sensitivity to Cbn BM1. Indeed,
      these approaches enable visualizing morphological damage of C. maltaromaticum
      DSM20730 only in an active dividing state. To specifically address the
      interaction between peptide and bacterial membrane, fluorescence anisotropy
      measurements were conducted. Results revealed strong modifications in membrane
      fluidity by Cbn BM1 only for C. maltaromaticum DSM20730 in log growth phase. In a
      similar way, the Deltapsi component, but not the DeltapH component of the proton
      motive force, was perturbed only for bacteria in log growth phase. These results
      clearly show that a class IIa bacteriocin antimicrobial mechanism of action can
      be modulated by the physiological state of its target bacteria.

PMID- 22588176
TI  - Source apportionment in oil spill remediation.
AB  - A pipe rupture during unloading led to a spillage of 350-700 tonnes of Cano
      Limon, a light sweet crude oil, into San Vicente Bay in 2007. Initial clean-up
      methods removed the majority of the oil from the sandy beaches although some oil
      remained on the rocky shores. It was necessary for the responsible party to clean
      the spilled oil even though at this location there were already crude oil
      hydrocarbons from previous industrial activity. A biosolvent based on vegetable
      oil derivatives was used to solubilise the remaining oil and a statistical
      approach to source apportionment was used to determine the efficacy of the
      cleaning. Sediment and contaminated rock samples were taken prior to cleaning and
      again at the same locations two days after application of the biosolvent. The oil
      was extracted using a modified USEPA Method 3550B. The alkanes were quantified
      together with oil biomarkers on a GC-MS. The contribution that Cano Limon made to
      the total oil hydrocarbons was calculated from a Partial Least Squares (PLS)
      analysis using Cano Limon crude oil as the source. By the time the biosolvent was
      applied, there had already been some attenuation of the oil with all alkanes
      <C(16) removed. After treatment, more of the mid-chain length compounds had been
      removed leading a skew towards the longer chain length compounds in the samples.
      The steranes provided a good indication of the source of the oil in this case and
      the contribution that Cano Limon made to the total oil ranged from 0% to 74%. The
      total hydrocarbon concentrations were lower after cleaning indicating an efficacy
      of 90% although the reduction in Cano Limon oil was smaller. This was sufficient
      to make further remediation unnecessary.

PMID- 22588177
TI  - The effect of combination therapy on the plasma concentrations of traditional
      antiepileptics: a retrospective study.
AB  - The present study aimed at determining the differences in plasma concentrations
      of traditional antiepileptics such as phenytoin, carbamazepine, and valproic acid
      in patients receiving monotherapy and combination therapy. In addition, the
      effect of gender and age on plasma drug concentration was evaluated in these
      patients. For this purpose, plasma trough concentrations obtained during routine
      therapeutic monitoring of these drugs were assessed retrospectively. The average
      plasma concentrations reached the apparent therapeutic ranges, except for the
      average plasma concentration of phenytoin, which was below the therapeutic range
      in patients who received only phenytoin or in combination with the other agents.
      Phenytoin when combined with carbamazepine or valproic acid significantly
      decreased the average plasma concentrations of these drugs to subtherapeutic
      concentrations. The results showed that plasma carbamazepine concentrations were
      higher in men than in women, whereas plasma concentrations of valproic acid and
      phenytoin were higher in women than in men. The difference in this regard between
      men and women was found to be statistically significant for phenytoin. The
      difference between the average plasma concentrations of carbamazepine, phenytoin,
      and valproic acid among age groups was not significant. In conclusion, our study
      measured the average plasma antiepileptic drug concentrations in patients with
      epilepsy who were receiving monotherapy and combination therapy and were
      routinely monitored, and has thus shown the importance of drug monitoring in the
      evaluation of the effectiveness of these drugs.

PMID- 22588178
TI  - Surgical staging for endometrial cancer in the elderly - is there a role for
      lymphadenectomy?
AB  - OBJECTIVES: We sought to evaluate the effect of systematic lymphadenectomy (LND)
      on endometrial cancer-specific survival in an elderly population. METHODS: Data
      were obtained from the Surveillance, Epidemiology, and End Results (SEER) program
      from 1988 to 2006. Women who underwent primary hysterectomy for non-serous, non
      clear cell endometrial carcinoma were included. Women were stratified by age
      (<70, 70-79, and >= 80) and disease-specific survival (DSS) was analyzed via the
      Kaplan-Meier method and stratified by postoperative grade. Cohorts were compared
      using the log-rank test. In a simulated population, the disease-specific survival
      of women with pre-operative grade 1 endometrial carcinoma was calculated using a
      weighted average survival accounting for those upgraded at final pathology.
      RESULTS: Endometrial cancer was identified in 5759 women >= 80 years old. Disease
      specific survival at 5 years for the LND and no LND groups was 93.4% and 94.5%
      (p=0.36) for grade 1, 84.4% and 85% (p=0.97) for grade 2, and 65.9% and 60.9%
      (p=0.002) for grade 3. In the simulated pre-operative grade 1 group, 5 year
      disease-specific survival (DSS) was 91% in the LND group and 92% in the no LND
      group. CONCLUSION: In women older than 80, systematic lymphadenectomy is
      associated with improved DSS for high grade, but similar DSS for low grade
      endometrial cancer, consistent with what is seen with younger women. As there is
      no clear survival benefit to lymphadenectomy in elderly women presenting with low
      grade disease, the surgeon should carefully weigh the surgical risks and benefits
      in this patient population, which may be at higher risk for morbidity.

PMID- 22588179
TI  - Summary of the 2012 American Association for Cancer Research (AACR) Annual
      Meeting.

PMID- 22588180
TI  - p16/Ki-67 dual staining in cervico-vaginal cytology: correlation with histology,
      Human Papillomavirus detection and genotyping in women undergoing colposcopy.
AB  - OBJECTIVES: To evaluate the CINtec PLUS assay (mtm laboratories), a new
      immunocytochemical method for the simultaneous detection of p16(INK4a) and Ki-67,
      in liquid-based cervico-vaginal cytology, investigating the association of the
      dual staining with HPV infection and genotyping as well as cytological and
      histological abnormalities. METHODS: 140 women with a cervico-vaginal sample
      obtained immediately before the colposcopy were enrolled. This cytological sample
      was used for HPV testing with the Linear Array HPV Genotyping Test, the dual
      staining with the CINtec PLUS kit and the morphology assessment. RESULTS:
      Cytology results were 38 NILM, 16 ASC-US, 32L-SIL, 54H-SIL or worse. 113 patients
      also had a colposcopy-guided biopsy, classified as 14 negative, 35 CIN1, 24 CIN2,
      37 CIN3, 3 invasive SCC. A strong association between p16/Ki-67 and HR-HPV
      infection was found (COR=6.86, 95% CI: 1.84-31.14). Importantly, the association
      between p16/Ki-67 positivity and HPV16 and/or 18 infection was 2-fold stronger
      compared to that with the infection by other HR-HPV types (COR=9.92, 95% CI: 2.39
      47.77 vs COR=4.20, 95% CI: 0.99-20.87). In addition, p16/Ki-67 positivity rate
      significantly increased with the severity of the cytological and histological
      abnormalities (p<0.05 in both cases). p16/Ki-67 positivity resulted strongly
      associated with a CIN2+ diagnosis (COR=10.86 95% CI: 4.16-29.12). CONCLUSIONS:
      This preliminary study evidenced that p16/Ki-67 immunostaining might have a
      relevant clinical role, since the dual staining was significantly associated with
      HR-HPV infection, particularly with HPV 16 and 18, and the increasing grade of
      the cervical lesions, the positivity for this biomarker being strongly related to
      the presence of a CIN2+ lesion.

PMID- 22588181
TI  - Titanate nanofunnel brushes: toward functional interfacial applications.
AB  - Titanate nanofunnel brushes were grown on sol-gel derived amorphous TiO(2) thin
      films, whose shape can be tuned from nanosheets to nanofunnels by changing
      hydrothermal conditions. A superhydrophobic adhesive surface was achieved by a
      chemical modification of the brushes.

PMID- 22588182
TI  - Risk of refracture associated with compliance and persistence with bisphosphonate
      therapy in Taiwan.
AB  - SUMMARY: Bisphosphonates have been used for the treatment of postmenopausal
      osteoporosis since the early 1990s and studies show that compliant patients
      experience a lower fracture rate. This cohort study showed that the compliance of
      Taiwanese patients was poor and the refracture risk was related to compliance
      with bisphosphonate therapy. INTRODUCTION: Bisphosphonates are potent inhibitors
      of osteoclast activity, and reduce bone turnover by inhibiting bone resorption.
      According to Taiwanese reimbursement guidelines, patients with osteoporosis
      related fractures are eligible for bisphosphonate treatment. This study aimed to
      elucidate the relationship of refracture risk with compliance/persistence with
      bisphosphonate therapy in Taiwan. METHODS: This was a retrospective,
      administrative, database analysis measuring the adherence status and impact of
      poor adherence to bisphosphonate therapy in Taiwan. Study data derived from the
      National Health Insurance Research Database (NHIRD) were used to assemble a
      cohort of all osteoporosis patients who initiated bisphosphonate treatment
      between January 1, 2004, and December 31, 2005. Patients were followed until
      death, end of registration in NHIRD, or end of study period (December 31, 2006),
      whichever occurred first. Compliance was calculated as medication possession
      ratio (MPR; sum of days of supply of osteoporosis medications divided by follow
      up duration). RESULTS: The refracture rates for osteoporosis patients were 5.15
      %, 7.36 %, and 8.49 % in the first, second, and third year, respectively, and
      were significantly lower for patients with >80 % compliance than with <80 %
      compliance (p < 0.05). Nearly 50 % patients were noncompliant (MPR < 80 %) at 3
      months, and only around 30 % patients were adherent at 1 year. Refracture risk
      increased with MPR < 80 %, age, and co-morbidities like diabetes mellitus or
      dementia. Patients with concomitant statin medication had significantly lower
      refracture risk. CONCLUSIONS: The compliance of Taiwanese patients with
      osteoporosis medication is poor, and refracture risk is related to compliance
      with bisphosphonate therapy.

PMID- 22588183
TI  - MENOPOST--calcium and vitamin D supplementation in postmenopausal osteoporosis
      treatment: a descriptive cohort study.
AB  - SUMMARY: Adequate vitamin D/calcium supplementation during osteoporosis (OP)
      treatments seems insufficient. This cohort study within a national claims
      database evaluated calcium/vitamin D co-prescription in postmenopausal women
      initiating an OP treatment. A high co-prescription rate was observed with three
      quarters of women supplemented with calcium and/or vitamin D in agreement with
      current recommendations. INTRODUCTION: Adequate calcium/vitamin D supplementation
      should be taken in combination with antiresorptive drugs in OP treatment. Despite
      guidelines, supplementation appears to be insufficient. The objective of this
      study was to describe and estimate co-prescription rates of calcium/vitamin D
      among postmenopausal women initiating an OP treatment. METHODS: All women over 50
      years with a first claim for a bisphosphonates, raloxifene, or strontium
      prescription filled between May and August 2010 were included in a retrospective
      cohort study. Data source was the health insurance claims database of the Rhone
      Alpes area. RESULTS: Among 4,415 women, 77.0 % had co-prescription of calcium or
      vitamin D with initial OP treatment, of which 2,150 (49.7 %) had both calcium and
      vitamin D. The proportion of women with calcium and/or vitamin D (81.7 %) was
      significantly higher when OP treatment was a bisphosphonate compared to strontium
      (70.9 %) or raloxifene (67.0 %) (p < 0.05). Among women prescribed both calcium
      and vitamin D, 7.6 % received a bisphosphonate and vitamin D +/- calcium fixed
      combination pack. General practitioners prescribed two thirds of initial
      supplementation treatment (66.9 %). Patients were twice as likely to be
      prescribed supplementation when the prescriber was a rheumatologist (OR = 2; 95 %
      CI = 1.57-2.54). CONCLUSION: Three quarters of women initiating OP treatment were
      supplemented with calcium and/or vitamin D in agreement with current
      recommendations. This represents a high co-prescription rate.

PMID- 22588184
TI  - Discriminating sarcopenia in community-dwelling older women with high frequency
      of overweight/obesity: the Sao Paulo Ageing & Health Study (SPAH).
AB  - SUMMARY: The criteria most used for the definition of sarcopenia, those based on
      the ratio between the appendicular skeletal muscle mass (ASM) and the square of
      the height (h(2)) underestimate prevalence in overweight/obese people whereas
      another criteria consider ASM adjusted for total fat mass. We have shown that ASM
      adjusted for fat seems to be more appropriate for sarcopenia diagnosis.
      INTRODUCTION: Since the prevalence of overweight and obesity is a growing public
      health issue, the aim of this study was to evaluate the prevalence and risk
      factors associated with sarcopenia, based on these two criteria, among older
      women. METHODS: Six hundred eleven community-dwelling women were evaluated by
      specific questionnaire including clinical data. Body composition and bone mineral
      density were evaluated by dual X-ray absorptiometry. Logistic regression models
      were used to identify factors independently related to sarcopenia by ASM/h(2) and
      ASM adjusted for total fat mass criteria. RESULTS: The prevalence of
      overweight/obesity was high (74.3 %). The frequency of sarcopenia was lower using
      the criteria of ASM/h(2) (3.7 %) than ASM adjusted for fat (19.9 %) (P < 0.0001).
      We also note that less than 5 %(1/23) of sarcopenic women, according to ASM/h(2),
      had overweight/obesity, whereas 60 % (74/122) of sarcopenic women by ASM adjusted
      for fat had this complication. Using ASM/h(2), the associated factors observed in
      regression models were femoral neck T-score (OR = 1.90; 95 % CI 1.06-3.41; P =
      0.03) and current alcohol intake (OR = 4.13, 95 % CI 1.18-14.45, P = 0.03). In
      contrast, we have identified that creatinine (OR = 0.21; 95 % CI 0.07-0.63; P =
      0.005) and the White race (OR = 1.81; 95 % CI 1.15-2.84; P = 0.01) showed a
      significant association with sarcopenia using ASM adjusted for fat. CONCLUSIONS:
      In women with overweight/obesity, ASM adjusted for fat seems to be the more
      appropriate criteria for sarcopenia diagnosis. This finding has relevant public
      health implications, considering the high prevalence of overweight/obesity in
      older women.

PMID- 22588185
TI  - SHBG levels are associated with bone loss and vertebral fractures in patients
      with prostate cancer.
AB  - SUMMARY: Fractures are increased among prostate cancer patients. No data have
      been reported in patients with prostate cancer about the relation between serum
      sex hormone-binding globulin (SHBG) and bone metabolism. We found that SHBG
      levels were inversely related to bone mass and vertebral fractures in this
      population. INTRODUCTION: Fractures are increased among prostate cancer patients,
      especially those on androgen deprivation therapy (ADT), but few data are
      available on the role of SHBG in their bone status. Our objective was to analyze
      the relation between serum SHBG and bone metabolism in prostate cancer patients.
      METHODS: This is a cross-sectional study including 91 subjects with prostate
      cancer (54 % with ADT). We measured serum levels of SHBG and sex steroids, bone
      mineral density (BMD) by dual-energy X-ray absorptiometry, and prevalent
      radiographic vertebral fractures. RESULTS: SHBG levels were inversely related to
      BMD (femoral neck: r = -0.299, p = 0.00; total hip: r = -0.259, p = 0.019).
      Subjects with osteoporosis had higher SHBG concentrations than patients without
      osteoporosis (60.97 +/- 39.56 vs 44.45 +/- 23.32 nmol/l, p = 0.022). Patients
      with SHBG levels in the first quartile (>57.6 nmol/l) had an odds ratio (OR) for
      osteoporosis of 2.59 (95 % CI, 1.30-5.12; p = 0.009) compared with patients with
      lower SHBG levels. In patients with SHBG >57.6 nmol/l, the OR for vertebral
      fractures was 2.34 (95 % CI, 1.15-4.78; p = 0.034). The calculated OR was higher
      after adjustment for age (OR, 5.16; 95 % CI, 1.09-24.49; p = 0.039), estrogens
      (OR, 6.45; 95 % CI, 1.44-28.95; p = 0.023), and androgens (OR, 5.51; 95 % CI,
      1.36-22.37; p = 0.017). CONCLUSIONS: In prostate cancer patients, SHBG levels
      were inversely related to bone mass and vertebral fractures. Determination of the
      serum SHBG level may constitute a useful and straightforward marker for
      predicting the severity of osteoporosis in these patients.

PMID- 22588186
TI  - Quantification of atherosclerotic plaque activity and vascular inflammation using
      [18-F] fluorodeoxyglucose positron emission tomography/computed tomography (FDG
      PET/CT).
AB  - Conventional non-invasive imaging modalities of atherosclerosis such as coronary
      artery calcium (CAC) and carotid intimal medial thickness (C-IMT) provide
      information about the burden of disease. However, despite multiple validation
      studies of CAC, and C-IMT, these modalities do not accurately assess plaque
      characteristics, and the composition and inflammatory state of the plaque
      determine its stability and, therefore, the risk of clinical events. [(18)F]-2
      fluoro-2-deoxy-D-glucose (FDG) imaging using positron-emission tomography
      (PET)/computed tomography (CT) has been extensively studied in oncologic
      metabolism. Studies using animal models and immunohistochemistry in humans show
      that FDG-PET/CT is exquisitely sensitive for detecting macrophage activity, an
      important source of cellular inflammation in vessel walls. More recently, we and
      others have shown that FDG-PET/CT enables highly precise, novel measurements of
      inflammatory activity of activity of atherosclerotic plaques in large and medium
      sized arteries. FDG-PET/CT studies have many advantages over other imaging
      modalities: 1) high contrast resolution; 2) quantification of plaque volume and
      metabolic activity allowing for multi-modal atherosclerotic plaque
      quantification; 3) dynamic, real-time, in vivo imaging; 4) minimal operator
      dependence. Finally, vascular inflammation detected by FDG-PET/CT has been shown
      to predict cardiovascular (CV) events independent of traditional risk factors and
      is also highly associated with overall burden of atherosclerosis. Plaque activity
      by FDG-PET/CT is modulated by known beneficial CV interventions such as short
      term (12 week) statin therapy as well as longer term therapeutic lifestyle
      changes (16 months). The current methodology for quantification of FDG uptake in
      atherosclerotic plaque involves measurement of the standardized uptake value
      (SUV) of an artery of interest and of the venous blood pool in order to calculate
      a target to background ratio (TBR), which is calculated by dividing the arterial
      SUV by the venous blood pool SUV. This method has shown to represent a stable,
      reproducible phenotype over time, has a high sensitivity for detection of
      vascular inflammation, and also has high inter-and intra-reader reliability. Here
      we present our methodology for patient preparation, image acquisition, and
      quantification of atherosclerotic plaque activity and vascular inflammation using
      SUV, TBR, and a global parameter called the metabolic volumetric product (MVP).
      These approaches may be applied to assess vascular inflammation in various study
      samples of interest in a consistent fashion as we have shown in several prior
      publications.

PMID- 22588187
TI  - Optimization of supervised cluster analysis for extracting reference tissue input
      curves in (R)-[(11)C]PK11195 brain PET studies.
AB  - Performance of two supervised cluster analysis (SVCA) algorithms for extracting
      reference tissue curves was evaluated to improve quantification of dynamic (R)
      [(11)C]PK11195 brain positron emission tomography (PET) studies. Reference
      tissues were extracted from images using both a manually defined cerebellum and
      SVCA algorithms based on either four (SVCA4) or six (SVCA6) kinetic classes. Data
      from controls, mild cognitive impairment patients, and patients with Alzheimer's
      disease were analyzed using various kinetic models including plasma input, the
      simplified reference tissue model (RPM) and RPM with vascular correction
      (RPMV(b)). In all subject groups, SVCA-based reference tissue curves showed lower
      blood volume fractions (V(b)) and volume of distributions than those based on
      cerebellum time-activity curve. Probably resulting from the presence of specific
      signal from the vessel walls that contains in normal condition a significant
      concentration of the 18 kDa translocation protein. Best contrast between subject
      groups was seen using SVCA4-based reference tissues as the result of a lower
      number of kinetic classes and the prior removal of extracerebral tissues. In
      addition, incorporation of V(b) in RPM improved both parametric images and
      binding potential contrast between groups. Incorporation of V(b) within RPM,
      together with SVCA4, appears to be the method of choice for analyzing cerebral
      (R)-[(11)C]PK11195 neurodegeneration studies.

PMID- 22588188
TI  - No evidence for additional blood-brain barrier P-glycoprotein dysfunction in
      Alzheimer's disease patients with microbleeds.
AB  - Decreased blood-brain barrier P-glycoprotein (Pgp) function has been shown in
      Alzheimer's disease (AD) patients using positron emission tomography (PET) with
      the radiotracer (R)-[(11)C]verapamil. Decreased Pgp function has also been
      hypothesized to promote cerebral amyloid angiopathy (CAA) development. Here, we
      used PET and (R)-[(11)C]verapamil to assess Pgp function in eighteen AD patients,
      of which six had microbleeds (MBs), presumably reflecting underlying CAA. No
      differences were found in binding potential and nonspecific volume of
      distribution of (R)-[(11)C]verapamil between patient groups. These results
      provide no evidence for additional Pgp dysfunction in AD patients with MBs.

PMID- 22588190
TI  - Current world literature. Translational research in wasting diseases.

PMID- 22588189
TI  - Malnutrition screening tools for hospitalized children.
AB  - PURPOSE OF REVIEW: Malnutrition is highly prevalent in hospitalized children and
      has been associated with relevant clinical outcomes. The scope of this review is
      to describe the five screening tools and the recent European Society for
      Parenteral and Enteral Nutrition (ESPEN) research project aimed at establishing
      agreed, evidence-based criteria for malnutrition and screening tools for its
      diagnosis in hospitalized children. RECENT FINDINGS: Five nutrition screening
      tools have recently been developed to identify the risk of malnutrition in
      hospitalized children. These tools have been tested to a limited extent by their
      authors in the original published studies but have not been validated by other
      independent studies. So far, such screening tools have not been established
      widely as part of standard pediatric care. SUMMARY: Although nutrition screening
      and assessment are recommended by European Society for Parenteral and Enteral
      Nutrition and the European Society for Pediatric Gastroenterology Hepatology and
      Nutrition and are often accepted to be required by healthcare facilities, there
      is no standardized approach to nutritional screening for pediatric inpatients.
      The near future will provide us with comparative data on the existing tools which
      may contribute to delineating a standard for useful nutrition screening in
      pediatrics.

PMID- 22588192
TI  - Amide-induced phase separation of hexafluoroisopropanol-water mixtures depending
      on the hydrophobicity of amides.
AB  - Amide-induced phase separation of hexafluoro-2-propanol (HFIP)-water mixtures has
      been investigated to elucidate solvation properties of the mixtures by means of
      small-angle neutron scattering (SANS), (1)H and (13)C NMR, and molecular dynamics
      (MD) simulation. The amides included N-methylformamide (NMF), N-methylacetamide
      (NMA), and N-methylpropionamide (NMP). The phase diagrams of amide-HFIP-water
      ternary systems at 298 K showed that phase separation occurs in a closed-loop
      area of compositions as well as an N,N-dimethylformamide (DMF) system previously
      reported. The phase separation area becomes wider as the hydrophobicity of amides
      increases in the order of NMF < NMA < DMF < NMP. Thus, the evolution of HFIP
      clusters around amides due to the hydrophobic interaction gives rise to phase
      separation of the mixtures. In contrast, the disruption of HFIP clusters causes
      the recovery of the homogeneity of the ternary systems. The present results
      showed that HFIP clusters are evolved with increasing amide content to the lower
      phase separation concentration in the same mechanism among the four amide
      systems. However, the disruption of HFIP clusters in the NMP and DMF systems with
      further increasing amide content to the upper phase separation concentration
      occurs in a different way from those in the NMF and NMA systems.

PMID- 22588193
TI  - Spa therapy of upper respiratory tract inflammations.
AB  - The upper airway respiratory diseases (i.e. common cold, allergic rhinitis,
      nonallergic/vasomotor rhinitis, acute and chronic rhinosinusitis and nasal
      polyposis) in which nasal congestion is a common symptom are often undertreated
      due to the frequent inadequate efficacy and safety concern with current
      therapies. In scientific literature, few studies seem to support the hypothesis
      that nasal inhalatory treatment with thermal water promotes the improvement of
      nasal symptoms, even if the mechanisms by which the improvement from SPA therapy
      can be expected remain debated. A prospective comparative study with a pre-post
      design has been performed consecutively enrolling 33 (males 70 %) patients of
      both genders older than 12 years of age, affected by chronic sinonasal
      inflammation. All patients underwent a 14-days course of radioactive water warm
      vapour inhalations followed by nasal aerosol of the same thermal water 10 min
      each once/day at Merano Therme. At the beginning and end of the study, in all the
      subjects, nasal function evaluation by active anterior rhinomanometry,
      mucociliary transport time (MCTt) determination and nasal cytology were
      performed. After the inhalatory treatment, the mucociliary function was improved
      and the pathologic mucociliary transport times recorded at the beginning of the
      study being significantly reduced to physiologic ones. Besides, before treatment,
      the cytologic picture showed an inflammatory cell infiltration (eosinophils,
      neutrophils with/without bacteria, mast cells) in 37 % of patients; after therapy
      in 66 % of these patients, the rhinocytogram was normal. Our results suggest,
      according to the literature data, that SPA therapy with radioactive water could
      represent an alternative choice in chronic inflammatory diseases of the upper
      airways, nonresponsive to pharmacological therapy.

PMID- 22588194
TI  - Inflammatory myofibroblastic tumors of the head and neck: evaluation of
      clinicopathologic and prognostic features.
AB  - Head and neck lesions composed of spindle cells evoke a differential diagnosis
      which includes a host of benign and malignant entities. One of the less common
      spindle cell lesions in this region is the inflammatory myofibroblastic tumor
      (IMT). Although IMTs were originally regarded as "pseudotumors", they are now
      recognized to be true neoplasms. Local recurrence, and, rarely, malignant change
      have been reported. Currently, the definitive means of diagnosing IMTs is the
      identification of a rearrangement of the anaplastic lymphoma kinase gene (at
      chromosome 2p23) by fluorescence in situ hybridization. The histopathologic
      differential diagnosis includes infectious processes, other fibro-inflammatory
      lesions, lymphoma, the inflammatory variant of malignant fibrous histiocytoma,
      and sarcomatoid (spindle cell) carcinoma. Complete surgical excision is the
      treatment of choice.

PMID- 22588195
TI  - The clinical impact of p16 status in fine-needle aspirates of cervical lymph node
      metastasis of head and neck squamous cell carcinomas.
AB  - Lymph node involvement is prognostically the most determinant clinical factor for
      patients with head and neck squamous cell carcinomas (HNSCCs). Ultrasound of the
      neck and fine-needle aspiration (FNA) cytology is one of the first diagnostic
      procedures and the most accurate diagnostic staging tool for the neck. Patients
      with HPV-positive oropharyngeal carcinomas (OPSCC) show a significantly better
      prognosis when compared with HPV-negative OPSCC. P16 overexpression is accepted
      as surrogate marker for HPV-positive in OPSCC. These HPV/p16-positive OPSCC are
      localized either in the palatal tonsils or the base of tongue and frequently
      present with lymph node metastases. We analyzed the correlation and reliability
      of p16 expression of the FNA of the lymph node metastasis with the
      immunohistochemical expression of p16 of the same lymph node metastasis and its
      corresponding primary tumor, as it could be of importance for determining the
      localization and different prognosis of the primary tumor. 54 HNSCC patients were
      evaluated, p16 expression of the primary tumors and their lymph node metastases
      correlated precisely. In 25 of the 54 HNSCC patients, a FNA of the lymph node
      metastases was taken before the treatment. The positive cytological and
      immunohistochemical p16 staining correlated exactly. Of the 17 histologically p16
      negative lymph node metastases 15 FNA were p16-negative, whereas two samples were
      p16-positive. In our view, a cytological p16 analysis of cervical lymph node
      metastasis can facilitate the correct localization of the primary tumor and
      discriminate reliably HPV-positive OPSCC from HPV-negative HNSCC with their
      significantly diverse prognosis.

PMID- 22588196
TI  - The necessity of post-maneuver postural restriction in treating benign paroxysmal
      positional vertigo: a meta-analytic study.
AB  - The objective of this article is to verify the role of postural restrictions
      after repositioning maneuvers in treating patients with benign paroxysmal
      positional vertigo (BPPV). The study included published articles yielded by a
      Pubmed search concerning post-maneuver postural restriction in treating BPPV. The
      search was limited to articles published in English language in the last three
      decades. The search was done on 1/11/2011. For the 18 relevant articles, we
      applied our inclusion and exclusion criteria and only 9 articles were included.
      The data collected from each article were statistically analyzed utilizing meta
      analytic Review Manager (RevMan 5.1) software. (Version: 5.1.0.0). There were no
      significant differences between patients instructed with postural restriction
      after undergoing repositioning maneuver and patients left free to move after
      undergoing repositioning maneuver with regard to the presence or absence of post
      maneuver symptoms. In conclusion, post-maneuver restrictions do not add to the
      success of the treatment of BPPV and there is no reason to submit patients to
      these impractical instructions.

PMID- 22588197
TI  - Transmission of human papillomavirus DNA from patient to surgical masks, gloves
      and oral mucosa of medical personnel during treatment of laryngeal papillomas and
      genital warts.
AB  - The risk of occupational human papillomavirus (HPV) transmission from patient to
      medical personnel during laser vaporization procedures remains controversial. The
      purpose of this study was to determine the risk of HPV transmission from the
      patient to the protective surgical masks, gloves and oral mucosa of medical
      personnel during the treatment of laryngeal papillomas and genital warts. The
      study involved five male patients scheduled for the surgical treatment of
      laryngeal papillomas, and five male patients undergoing carbon dioxide (CO(2))
      laser treatment for urethral warts. Oral mucosa specimens were obtained from the
      study patients and the employees pre- and postoperatively. Samples were collected
      from the HPV-infected patient tissue, and from the surgical masks and gloves used
      by the employees. A total of 120 samples were analyzed for the presence of HPV
      DNA by PCR, using the degenerated MY09/11/HMB01 primers. After the papilloma
      procedures, the surgeons' gloves tested HPV positive in one of the five cases and
      those of the surgical nurse in three of the five cases. After the treatment of
      genital warts, HPV DNA corresponding to the patient tissue specimens was present
      in all the samples obtained from the surgical gloves of the operators. All oral
      mucosa samples obtained from 18 different employees tested HPV negative, as did
      the surgical mask specimens. According to our study, HPV may contaminate
      protective equipment, most of all surgical gloves, but transmission of HPV DNA to
      medical personnel is unlikely to occur provided that protective surgical gloves
      and masks are applied and disposed of properly.

PMID- 22588198
TI  - The role of culture in substance abuse treatment programs for American Indian and
      Alaska Native communities.
AB  - OBJECTIVE: Culture figures prominently in discussions regarding the etiology of
      alcohol and substance abuse in American Indian and Alaska Native (AI/AN)
      communities, and a substantial body of literature suggests that it is critical to
      developing meaningful treatment interventions. However, no study has
      characterized how programs integrate culture into their services. Furthermore,
      reports regarding the associated challenges are limited. METHODS: Twenty key
      informant interviews with administrators and 15 focus groups with clinicians were
      conducted in 18 alcohol and substance abuse treatment programs serving AI/AN
      communities. Transcripts were coded to identify relevant themes. RESULTS:
      Substance abuse treatment programs for AI/AN communities are integrating culture
      into their services in two discrete ways: by implementing specific cultural
      practices and by adapting Western treatment models. More important, however, are
      the fundamental principles that shape these programs and their interactions with
      the people and communities they serve. These foundational beliefs and values,
      defined in this study as the core cultural constructs that validate and
      incorporate AI/AN experience and world view, include an emphasis on community and
      family, meaningful relationships with and respect for clients, a homelike
      atmosphere within the program setting, and an "open door" policy for clients. The
      primary challenges for integrating these cultural practices include AI/AN
      communities' cultural diversity and limited socioeconomic resources to design and
      implement these practices. CONCLUSIONS: The prominence of foundational beliefs
      and values is striking and suggests a broader definition of culture when
      designing services. This definition of foundational beliefs and values should
      help other diverse communities culturally adapt their substance abuse
      interventions in more meaningful ways.

PMID- 22588199
TI  - Evaluation of the behavioral and pharmacokinetic profile of SYA013, a
      homopiperazine analog of haloperidol in rats.
AB  - SYA013, a homopiperazine analog of haloperidol, was further evaluated for
      antipsychotic potential using additional animal models. Previously, SYA013 was
      tested in mice with an antipsychotic screening model in which it inhibited
      apomorphine induced climbing behavior, indicating antagonism of the dopaminergic
      system and the potential for use in the treatment of schizophrenia. In this
      study, SYA013 was shown to inhibit both d-amphetamine-induced locomotor activity
      in rats and conditioned avoidance response (CAR) in rats in a dose dependent
      manner and in the case of CAR, without producing any escape failure responses
      (EFRs), two tests predictive of antipsychotic action. The selective 5HT(1A)
      antagonist WAY100,635 was used to determine if binding of SYA013 to the 5HT(1A)
      receptor contributed to suppression of CAR. The results indicated that 0.63mg/kg
      WAY100,635 did not have a significant effect on the inhibition of CAR by SYA013.
      Pharmacokinetic parameters in brain and plasma were determined for SYA013. A log
      brain/plasma concentration ratio at a t(max) of 1.48 suggests that SYA013 readily
      crosses the blood brain barrier (BBB). The hypothesis that binding of SYA013 to
      the 5HT(1A) receptor contributed to the lack of significant catalepsy was
      investigated using the 5HT(1A) antagonist WAY100,635. The results of acute and
      semi-chronic tests suggest that binding to the 5HT(1A) receptor alone did not
      significantly account for the lack of catalepsy. Lack of catalepsy was preserved
      after the semi-chronic challenge with SYA013. These tests further indicate that
      SYA013 has a pharmacological profile with the potential for use in the treatment
      of neuropsychiatric diseases. In addition, the 5HT(1A) receptor does not appear
      to play a significant role in the pharmacological profile of SYA013.

PMID- 22588200
TI  - Organosilane micellization for direct encapsulation of hydrophobic quantum dots
      into silica beads with highly preserved fluorescence.
AB  - Effective silica coating on hydrophobic quantum dots (QDs) was achieved by
      ultrasonic fragmentation of lipophilic silane-QDs precusor into water-soluble
      micelles and subsequent silicate deposition. This method allowed high retention
      of QD fluorescent properties and an easy scaling over the size and loading amount
      of silica beads.

PMID- 22588201
TI  - Applying an animal model to quantify the uncertainties of an image-based 4D-CT
      algorithm.
AB  - The purpose of this paper is to use an animal model to quantify the spatial
      displacement uncertainties and test the fundamental assumptions of an image-based
      4D-CT algorithm in vivo. Six female Landrace cross pigs were ventilated and
      imaged using a 64-slice CT scanner (GE Healthcare) operating in axial cine mode.
      The breathing amplitude pattern of the pigs was varied by periodically crimping
      the ventilator gas return tube during the image acquisition. The image data were
      used to determine the displacement uncertainties that result from matching CT
      images at the same respiratory phase using normalized cross correlation (NCC) as
      the matching criteria. Additionally, the ability to match the respiratory phase
      of a 4.0 cm subvolume of the thorax to a reference subvolume using only a single
      overlapping 2D slice from the two subvolumes was tested by varying the location
      of the overlapping matching image within the subvolume and examining the effect
      this had on the displacement relative to the reference volume. The displacement
      uncertainty resulting from matching two respiratory images using NCC ranged from
      0.54 +/- 0.10 mm per match to 0.32 +/- 0.16 mm per match in the lung of the
      animal. The uncertainty was found to propagate in quadrature, increasing with
      number of NCC matches performed. In comparison, the minimum displacement
      achievable if two respiratory images were matched perfectly in phase ranged from
      0.77 +/- 0.06 to 0.93 +/- 0.06 mm in the lung. The assumption that subvolumes
      from separate cine scan could be matched by matching a single overlapping 2D
      image between to subvolumes was validated. An in vivo animal model was developed
      to test an image-based 4D-CT algorithm. The uncertainties associated with using
      NCC to match the respiratory phase of two images were quantified and the
      assumption that a 4.0 cm 3D subvolume can by matched in respiratory phase by
      matching a single 2D image from the 3D subvolume was validated. The work in this
      paper shows the image-based 4D-CT algorithm to be a promising method for
      producing 4D-CT images for radiotherapy.

PMID- 22588202
TI  - Chemically-blocked antibody microarray for multiplexed high-throughput profiling
      of specific protein glycosylation in complex samples.
AB  - In this study, we describe an effective protocol for use in a multiplexed high
      throughput antibody microarray with glycan binding protein detection that allows
      for the glycosylation profiling of specific proteins. Glycosylation of proteins
      is the most prevalent post-translational modification found on proteins, and
      leads diversified modifications of the physical, chemical, and biological
      properties of proteins. Because the glycosylation machinery is particularly
      susceptible to disease progression and malignant transformation, aberrant
      glycosylation has been recognized as early detection biomarkers for cancer and
      other diseases. However, current methods to study protein glycosylation typically
      are too complicated or expensive for use in most normal laboratory or clinical
      settings and a more practical method to study protein glycosylation is needed.
      The new protocol described in this study makes use of a chemically blocked
      antibody microarray with glycan-binding protein (GBP) detection and significantly
      reduces the time, cost, and lab equipment requirements needed to study protein
      glycosylation. In this method, multiple immobilized glycoprotein-specific
      antibodies are printed directly onto the microarray slides and the N-glycans on
      the antibodies are blocked. The blocked, immobilized glycoprotein-specific
      antibodies are able to capture and isolate glycoproteins from a complex sample
      that is applied directly onto the microarray slides. Glycan detection then can be
      performed by the application of biotinylated lectins and other GBPs to the
      microarray slide, while binding levels can be determined using Dylight 549
      Streptavidin. Through the use of an antibody panel and probing with multiple
      biotinylated lectins, this method allows for an effective glycosylation profile
      of the different proteins found in a given human or animal sample to be
      developed.

PMID- 22588203
TI  - Phycoerythrin evolution and diversification of spectral phenotype in marine
      Synechococcus and related picocyanobacteria.
AB  - In marine Synechococcus there is evidence for the adaptive evolution of
      spectrally distinct forms of the major light harvesting pigment phycoerythrin
      (PE). Recent research has suggested that these spectral forms of PE have a
      different evolutionary history than the core genome. However, a lack of explicit
      statistical testing of alternative hypotheses or for selection on these genes has
      made it difficult to evaluate the evolutionary relationships between spectral
      forms of PE or the role horizontal gene transfer (HGT) may have had in the
      adaptive phenotypic evolution of the pigment system in marine Synechococcus. In
      this work, PE phylogenies of picocyanobacteria with known spectral phenotypes,
      including newly co-isolated strains of marine Synechococcus from the Gulf of
      Mexico, were constructed to explore the diversification of spectral phenotype and
      PE evolution in this group more completely. For the first time, statistical
      evaluation of competing evolutionary hypotheses and tests for positive selection
      on the PE locus in picocyanobacteria were performed. Genes for PEs associated
      with specific PE spectral phenotypes formed strongly supported monophyletic
      clades within the PE tree with positive directional selection driving evolution
      towards higher phycourobilin (PUB) content. The presence of the PUB-lacking
      phenotype in PE-containing marine picocyanobacteria from cyanobacterial lineages
      identified as Cyanobium is best explained by HGT into this group from marine
      Synechococcus. Taken together, these data provide strong examples of adaptive
      evolution of a single phenotypic trait in bacteria via mutation, positive
      directional selection and horizontal gene transfer.

PMID- 22588204
TI  - Chemotherapy and molecular-targeted treatment for unresectable hepatic
      metastases: a Japanese perspective.
AB  - Liver metastasis from colorectal cancer has become a common disease associated
      with the increase of primary colorectal cancer in Japan. The standard treatment
      for resectable liver metastases is still complete liver resection. Recent
      advances in systemic chemotherapy have introduced another strategy, i.e.,
      conversion chemotherapy, for patients with initially diagnosed unresectable liver
      metastases. The conversion rate after neo-adjuvant chemotherapy is increasing
      with multidisciplinary approaches. Long-term clinical data have not been
      established yet. Indications for liver resection after neo-adjuvant chemotherapy;
      optimal chemotherapy regimens; and histological changes in the normal liver are
      important research issues for the future.

PMID- 22588205
TI  - Bioconversion of alpha-linolenic acid to n-3 LCPUFA and expression of PPAR-alpha,
      acyl Coenzyme A oxidase 1 and carnitine acyl transferase I are incremented after
      feeding rats with alpha-linolenic acid-rich oils.
AB  - High dietary intake of n-6 fatty acids in relation to n-3 fatty acids may
      generate health disorders, such as cardiovascular and other chronic diseases.
      Fish consumption rich in n-3 fatty acids is low in Latin America, it being
      necessary to seek other alternatives to provide alpha-linolenic acid (ALA),
      precursor of n-3 LCPUFA (EPA and DHA). Two innovative oils were assayed, chia
      (Salvia hispanica) and rosa mosqueta (Rosa rubiginosa). This study evaluated
      hepatic bioconversion of ALA to EPA and DHA, expression of PPAR-alpha, acyl
      Coenzyme A oxidase 1 (ACOX1) and carnitine acyltransferase I (CAT-I), and
      accumulation of EPA and DHA in plasma and adipose tissue in Sprague-Dawley rats.
      Three experimental groups were fed 21 days: sunflower oil (SFO, control); chia
      oil (CO); rosa mosqueta oil (RMO). Fatty acid composition of total lipids and
      phospholipids from plasma, hepatic and adipose tissue was assessed by gas-liquid
      chromatography and TLC. Expression of PPAR-alpha (RT-PCR) and ACOX1 and CAT-I
      (Western blot). CO and RMO increased plasma, hepatic and adipose tissue levels of
      ALA, EPA and DHA and decreased n-6:n-3 ratio compared to SFO (p < 0.05, One-way
      ANOVA and Newman-Keuls test). CO increased levels of ALA and EPA compared to RMO
      (p < 0.05). No significant differences were observed for DHA levels. CO also
      increased the expression of PPAR-alpha, ACOX1 and CAT-I. Only CAT-I levels were
      increased by RO. CO and RMO may be a nutritional alternative to provide ALA for
      its bioconversion to EPA and DHA, and to increase the expression of PPAR-alpha,
      ACOX1 and CAT-I, especially CO-oil.

PMID- 22588206
TI  - Successful surgical repair of a giant coronary-pulmonary artery fistula: role of
      magnetic resonance imaging.

PMID- 22588207
TI  - Prediction of 9-year cardiovascular outcomes by myocardial perfusion imaging in
      patients with normal exercise electrocardiographic testing.
AB  - AIMS: Exercise myocardial perfusion imaging (MPI) is widely used, but the long
      term prognostic value of this test in patients with normal exercise
      electrocardiographic testing is not defined. METHODS AND RESULTS: A consecutive
      group of 650 patients (428 men, mean age: 56 +/- 11 years) with known or
      suspected coronary artery disease underwent exercise electrocardiographic testing
      and MPI. Follow-up endpoints were mortality and major adverse cardiac events
      (MACE). Predictors of outcome were identified by multivariate logistic regression
      analysis using clinical, exercise electrocardiographic testing and single-photon
      emission computed tomography (SPECT) variables. A total of 324 (50%) patients had
      an abnormal SPECT, and 131 (20%) had completely or partially reversible perfusion
      defects. During a mean follow-up of 9.2 +/- 2.0 years, 107 (23%) patients died,
      69 (11%) had a non-fatal myocardial infarction, 90 (14%) underwent coronary
      artery bypass surgery, and 142 (22%) percutaneous coronary intervention.
      Multivariate analysis demonstrated that the summed rest score was an independent
      predictor of mortality [hazard ratio (HR): 1.15, 95% confidence interval (CI):
      (1.08-1.22], P < 0.001). The summed stress score was an independent predictor of
      MACE [HR: 1.09, 95% CI: (1.04-1.13), P < 0.001]. The addition of SPECT variables
      to clinical and exercise electrocardiographic testing data provided incremental
      prognostic information for the prediction of mortality and MACE (both P < 0.001).
      CONCLUSION: Approximately 20% of patients with known or suspected coronary artery
      disease and normal exercise electrocardiographic testing have completely or
      partially reversible myocardial perfusion defects. MPI provides additional
      information for the prediction of 9-year cardiovascular outcomes in these
      patients.

PMID- 22588208
TI  - Closure of a large pulmonary arterio-venous fistula with Amplatzer vascular plug
      I.

PMID- 22588209
TI  - Validation of the isovolumetric relaxation time for the estimation of pulmonary
      systolic arterial blood pressure in chronic pulmonary hypertension.
AB  - AIMS: Transthoracic echocardiography is a useful technique for non-invasive
      detection of pulmonary arterial systolic pressure (PASP). Isovolumic relaxation
      time (IVRT) measured by Doppler tissue imaging (DTI) is a sensitive measurement
      of changes in pulmonary vasculature. Our aim was to validate IVRT in the
      echocardiographic assessment of pulmonary hypertension (PH) patients. METHODS AND
      RESULTS: We studied 196 PH patients (67% women, mean age 51.8 +/- 16.6 years,
      mean PASP: 81 +/- 24 mmHg) and 37 consecutive age- and sex-matched controls (58%
      women, mean age 44.7 +/- 16.4 years, mean PASP 27.7 +/- 5.5 mmHg). The estimation
      of PASP was derived from tricuspid regurgitation velocity according to the
      Bernoulli equation. The measurement of IVRT was calculated using pulsed tissue
      Doppler. In the PH group and in the healthy volunteers group (P < 0.0001), the
      average IVRT was 113.4 +/- 28.5 ms [95% confidence interval (CI): 109-117] and 41
      +/- 12.5 ms (95% CI: 37-45), respectively. We found a strong correlation between
      IVRT and systolic pulmonary pressure in the PH group (r = 0.52, P < 0.0001) and a
      cut-off of 75 ms showed a sensitivity and specificity of 94% and 97%,
      respectively, for the prediction of elevated PASP. CONCLUSION: The determination
      of IVRT by DTI is a simple and reproducible method that correlates well with
      PASP. It is, therefore, a parameter to consider in the echocardiographic
      assessment of patients with PH, and may be particularly important when the
      tricuspid Doppler signal is poor.

PMID- 22588210
TI  - An unusual cause of intractable cough.

PMID- 22588212
TI  - Effects of estrogen on vaginal innervation:  denervation or remodeling?

PMID- 22588213
TI  - Adiposity, body composition, and weight change in relation to organochlorine
      pollutant plasma concentrations.
AB  - We investigated cross-sectional associations of body composition and weight
      change with polychlorinated biphenyls (PCB) and organochlorine
      pesticides/pesticide metabolites measured in blood collected at the baseline of
      the Physical Activity for Total Health study of postmenopausal, overweight women
      living in the Seattle, Washington metropolitan area. Indicators of greater
      adiposity were associated with lower plasma concentrations of most PCBs with six
      or more chlorine atoms. This pattern was observed for current weight, body mass
      index, fat mass percent, subcutaneous abdominal fat, intra-abdominal fat, waist
      circumference, hip circumference, waist-to-hip ratio, and maximum adult weight.
      Conversely, PCB 105, PCB 118, and p,p'-DDE were generally increased or showed no
      association with these variables. Weight gain since age 35 was associated with
      lower concentrations of almost every organochlorine we studied, and past weight
      loss episodes of at least 20 pounds (>=9.1 kg) were associated with higher
      concentrations. Our results have implications for epidemiologic studies of
      organochlorines in terms of covariates that may be important to consider in
      statistical analyses, particularly as such considerations may differ importantly
      by specific analyte. Our finding of increased organochlorine concentrations with
      past weight loss episodes may have public health significance; however, this
      association requires confirmation in longitudinal studies.

PMID- 22588214
TI  - Interpreting variability in population biomonitoring data: role of elimination
      kinetics.
AB  - Biomarker concentrations in spot samples of blood and urine are implicitly
      interpreted as direct surrogates for long-term exposure magnitude in a variety of
      contexts including (1) epidemiological studies of potential health outcomes
      associated with general population chemical exposure, and (2) cross-sectional
      population biomonitoring studies. However, numerous factors in addition to
      exposure magnitude influence biomarker concentrations in spot samples, including
      temporal variation in spot samples because of elimination kinetics. The influence
      of half-life of elimination relative to exposure interval is examined here using
      simple first-order pharmacokinetic simulations of urinary concentrations in spot
      samples collected at random times relative to exposure events. Repeated exposures
      were modeled for each individual in the simulation with exposure amounts drawn
      from lognormal distributions with varying geometric standard deviations. Relative
      variation in predicted spot sample concentrations was greater than the variation
      in underlying dose distributions when the half-life of elimination was shorter
      than the interval between exposures, with the degree of relative variation
      increasing as the ratio of half-life to exposure interval decreased. Results of
      the modeling agreed well with data from a serial urine collection data set from
      the Centers for Disease Control. Data from previous studies examining intra-class
      correlation coefficients for a range of chemicals relying upon repeated sampling
      support the importance of considering the half-life relative to exposure
      frequency in design and interpretation of studies using spot samples for exposure
      classification and exposure estimation. The modeling and data sets presented here
      provide tools that can assist in interpretation of variability in cross-sectional
      biomonitoring studies and in design of studies utilizing biomonitoring data as
      markers for exposure.

PMID- 22588215
TI  - A Bayesian mixture modeling approach for assessing the effects of correlated
      exposures in case-control studies.
AB  - Predisposition to a disease is usually caused by cumulative effects of a
      multitude of exposures and lifestyle factors in combination with individual
      susceptibility. Failure to include all relevant variables may result in biased
      risk estimates and decreased power, whereas inclusion of all variables may lead
      to computational difficulties, especially when variables are correlated. We
      describe a Bayesian Mixture Model (BMM) incorporating a variable-selection prior
      and compared its performance with logistic multiple regression model (LM) in
      simulated case-control data with up to twenty exposures with varying prevalences
      and correlations. In addition, as a practical example we re analyzed data on male
      infertility and occupational exposures (Chaps-UK). BMM mean-squared errors (MSE)
      were smaller than of the LM, and were independent of the number of model
      parameters. BMM type I errors were minimal (<=1), whereas for the LM this
      increased with the number of parameters and correlation between exposures. The
      numbers of type II errors were comparable. Re analysis of Chaps-UK data
      demonstrated more convincingly than by using a LM that occupational exposure to
      glycol ethers and VOCs are likely risk factors for male infertility. This BMM
      proves an appealing alternative to standard logistic regression when dealing with
      the analysis of (correlated) exposures in case-control studies.

PMID- 22588216
TI  - Evaluation of urinary metabolites of 1-nitropyrene as biomarkers for exposure to
      diesel exhaust in taxi drivers of Shenyang, China.
AB  - Diesel exhaust (DE) is a significant contributor to the toxicity associated with
      particulate matter (PM). 1-Nitropyrene (1-NP) has been used as a molecular marker
      for DE, and the urinary metabolites of 1-NP have been proposed as biomarkers for
      exposure to DE. In this study, several urinary 1-NP metabolites were evaluated
      for their utility as markers of short-term exposures to DE. The study population
      was a cohort of 24 taxi drivers from Shenyang, China, who submitted urine samples
      collected before, after, and the next morning following their workshifts. The
      urinary metabolites studied were isomers of hydroxy-1-nitropyrene (3-, 6-, 8-
      OHNPs) and hydroxy-N-acetyl-1-aminopyrene (3-,6-, 8-OHNAAPs). Exposure to DE was
      estimated based on exposure to 1-NP in air samples collected during and after the
      driver's workshift; 6- and 8-OHNP, and 8-OHNAAP were consistently detected in the
      drivers' urine. Concentrations of the metabolites in the taxi drivers' urine were
      greater than metabolite levels previously reported in non-occupationally exposed
      subjects; however no associations were observed between subject-specific
      exposures to 1-NP and urinary metabolites measured at the end of the workshift or
      in the next morning void. Significant autocorrelation was observed in metabolite
      levels in successive urine samples, from which half-lives for urinary elimination
      of ~10-12 h were estimated. These observations suggest that, in an occupational
      setting, urinary 1-NP metabolites may be more suitable as markers of ongoing
      exposure (timescales of several days) rather than indicators of acute exposure
      associated with single workshifts.

PMID- 22588217
TI  - Probabilistic assessment of chlorpyrifos exposure to rice farmers in Viet Nam.
AB  - Chlorpyrifos is the most common organophosphate compound registered for
      agricultural use in Vietnam. The aim of this study was to evaluate chlorpyrifos
      exposure to rice farmers in Vietnam, using a probabilistic approach. Urine
      samples on a 24-h basis were collected from farmers before and post application
      of pesticide. Samples were analysed for 3,5,6-trichloro-2-pyridinol (TCP), the
      major urinary metabolite of chlorpyrifos, using an enzymatic pre-treatment for
      extraction and HPLC-MS/MS. Absorbed daily doses (ADD) of chlorpyrifos for farmers
      were subsequently estimated from the urinary TCP levels. The baseline and post
      application exposure levels were evaluated at the 5th, 50th, and 95th percentile
      representing low, medium and high-exposure groups in the population. Regression
      analysis was applied to examine the association between exposure level and
      factors. The baseline exposure level, which ranged from 0.03 to 1.98 MUg/kg/day
      was below the chronic guidelines recommended by international and national
      bodies. However, the post-application exposure level, which ranged from 0.35 to
      94 MUg/kg/day exceeded most of the acute guidelines at the 95th percentile level.
      Multivariate analysis provided strong evidence for a relationship between post
      application exposure level and amount of chlorpyrifos used, as well as body
      coverage of personal protective equipment.

PMID- 22588218
TI  - Exposure and health risk assessment of applicators to DDT during indoor residual
      spraying in malaria vector control program.
AB  - We assessed exposure of applicators, health risk of DDT to the applicators and
      evaluated the applicability of existing pesticide exposure models for indoor
      residual spraying (IRS). Patch sampling for dermal and personal air sampler for
      inhalation exposure were used in monitoring 57 applicators on the exposure
      assessment to DDT. The exposure of the applicators was also estimated using three
      exposure models. The mean actual dermal exposure was 449 mg total DDT per
      applicator per one house treatment. The applicators were exposed to DDT much
      beyond the estimated AOEL (acceptable operator exposure level) of DDT. The
      exposure estimated with ConsExpo 5.0 b01 model is situated between the median and
      the 75th percentile of the experimental data. On the other hand, spraying model 1
      and spraying model 10 overestimate the exposure. Thus, these three models cannot
      be directly used for the particular circumstances of IRS as a tool for risk
      assessment. In general, use of DDT in IRS as a control method for malaria
      mosquitoes holds a high health risk for the applicators. Strict implementation of
      spraying procedures stated in the IRS manual of World Health Organization (WHO)
      is necessary to reduce the exposure level and health risk of applicators to DDT.

PMID- 22588219
TI  - Multiple forms of perceived discrimination and health among adolescents and young
      adults.
AB  - Research on perceived discrimination has overwhelmingly focused on one form of
      discrimination, especially race discrimination, in isolation from other forms.
      The present article uses data from the Black Youth Culture Survey, a nationally
      representative, racially and ethnically diverse sample of 1,052 adolescents and
      young adults to investigate the prevalence, distribution, and mental and physical
      health consequences of multiple forms of perceived discrimination. The findings
      suggest that disadvantaged groups, especially multiply disadvantaged youth, face
      greater exposure to multiple forms of discrimination than their more privileged
      counterparts. The experience of multiple forms of discrimination is associated
      with worse mental and physical health above the effect of only one form and
      contributes to the relationship between multiple disadvantaged statuses and
      health. These findings suggest that past research may misspecify the
      discrimination-health relationship and fails to account for the disproportionate
      exposure to discrimination faced by multiply disadvantaged individuals.

PMID- 22588220
TI  - Humeral development from neonatal period to skeletal maturity--application in age
      and sex assessment.
AB  - The goal of the present study is to examine cross-sectional information on the
      growth of the humerus based on the analysis of four measurements, namely,
      diaphyseal length, transversal diameter of the proximal (metaphyseal) end of the
      shaft, epicondylar breadth and vertical diameter of the head. This analysis was
      performed in 181 individuals (90 ? and 91 ?) ranging from birth to 25 years of
      age and belonging to three documented Western European skeletal collections
      (Coimbra, Lisbon and St. Bride). After testing the homogeneity of the sample, the
      existence of sexual differences (Student's t- and Mann-Whitney U-test) and the
      growth of the variables (polynomial regression) were evaluated. The results
      showed the presence of sexual differences in epicondylar breadth above 20 years
      of age and vertical diameter of the head from 15 years of age, thus indicating
      that these two variables may be of use in determining sex from that age onward.
      The growth pattern of the variables showed a continuous increase and followed
      first- and second-degree polynomials. However, growth of the transversal diameter
      of the proximal end of the shaft followed a fourth-degree polynomial. Strong
      correlation coefficients were identified between humeral size and age for each of
      the four metric variables. These results indicate that any of the humeral
      measurements studied herein is likely to serve as a useful means of estimating
      sub-adult age in forensic samples.

PMID- 22588221
TI  - A five-gene cluster involved in utilization of taurine-nitrogen and excretion of
      sulfoacetaldehyde by Acinetobacter radioresistens SH164.
AB  - Acinetobacter calcoaceticus SW1, under nitrogen limitation, assimilates the
      nitrogen moiety of taurine (2-aminoethanesulfonate) inducibly and excretes
      sulfoacetaldehyde, a product of taurine dehydrogenase (TauXY). BLAST searches of
      newly available genome sequences using the TauXY sequences revealed a 5-gene
      cluster, tauRXYPI, in Acinetobacter radioresistens SH164. We hypothesized that
      tauXYPI (HMPREF0018_00717-HMPREF0018_00720) encodes proteins that are orthologs
      of the undefined pathway from strain SW1, and that tauR (HMPREF0018_00716)
      encodes the relevant transcriptional regulator. Strain SH164 excreted
      sulfoacetaldehyde from taurine during growth. TauXY activity was expressed
      inducibly. Reverse transcription PCR showed that the tauRXYPI genes were
      transcribed inducibly. This allowed the conclusions that (i) TauP (currently
      annotated as permease GabP [TC 2.A.3]) is a taurine permease, and (ii) TauI
      (currently annotated as DUF6 drug/metabolite exporter [TC 2.A.7]) is a
      sulfoacetaldehyde exporter. The presumably equifunctional cluster tauRXYPI was
      then found in strain SW1. TauP is the third recognized taurine uptake system, and
      TauI is the third postulated class of sulfonate exporters, in bacteria.

PMID- 22588222
TI  - Evaluating secretion and surface attachment of SapA, an S-layer-associated
      metalloprotease of Caulobacter crescentus.
AB  - Caulobacter crescentus is used to display foreign peptides at high density as
      insertions into the surface (S)-layer protein (RsaA). Many recombinant RsaA
      proteins, however, are cleaved by SapA, a 71-kDa metalloprotease, suggesting a
      role in maintaining S-layer integrity. When overexpressed on a multicopy plasmid
      SapA was detected on the surface by fluorescent antibody only if RsaA and the O
      side chain of LPS that mediates S-layer attachment were removed by mutation,
      indicating an outer membrane location beneath the S-layer. Secretion was mediated
      by the RsaA type 1 transporter since secretion was eliminated in transporter
      deficient strains or by C-terminal deletions in SapA (the presumed location of
      type 1 secretion signals). Secretion was required to become an active protease;
      mass spectrometry suggested this might be due to N-terminal processing during
      secretion, a feature shared with other type 1-secreted proteases. Overexpression
      leads to additional processing C-terminal to the protease domain, producing a 45
      kDa protein. This was demonstrated to be self-processing. Deletion analysis
      revealed the C-terminal 100 amino acids were sufficient for anchoring and
      secretion. When protein G was fused to the last 238 amino acids of SapA it was
      secreted, surface attached and bound immunoglobulin, indicating potential for
      foreign protein display.

PMID- 22588223
TI  - Improving the performance of a membraneless and mediatorless glucose-air biofuel
      cell with a TiO2 nanotube photoanode.
AB  - A new light-driven, membraneless and mediatorless glucose-air biofuel cell
      combining a TiO(2) nanotube photoanode with an enzyme-modified biocathode has
      been successfully constructed. Upon UV light illumination, the open-circuit
      voltage and the maximum power density of the cell reach 1.00 V and 47 MUW cm(-2),
      respectively.

PMID- 22588224
TI  - Attaching biological probes to silica optical biosensors using silane coupling
      agents.
AB  - In order to interface with biological environments, biosensor platforms, such as
      the popular Biacore system (based on the Surface Plasmon Resonance (SPR)
      technique), make use of various surface modification techniques, that can, for
      example, prevent surface fouling, tune the hydrophobicity/hydrophilicity of the
      surface, adapt to a variety of electronic environments, and most frequently,
      induce specificity towards a target of interest. These techniques extend the
      functionality of otherwise highly sensitive biosensors to real-world applications
      in complex environments, such as blood, urine, and wastewater analysis. While
      commercial biosensing platforms, such as Biacore, have well-understood, standard
      techniques for performing such surface modifications, these techniques have not
      been translated in a standardized fashion to other label-free biosensing
      platforms, such as Whispering Gallery Mode (WGM) optical resonators. WGM optical
      resonators represent a promising technology for performing label-free detection
      of a wide variety of species at ultra-low concentrations. The high sensitivity of
      these platforms is a result of their unique geometric optics: WGM optical
      resonators confine circulating light at specific, integral resonance frequencies.
      Like the SPR platforms, the optical field is not totally confined to the sensor
      device, but evanesces; this "evanescent tail" can then interact with species in
      the surrounding environment. This interaction causes the effective refractive
      index of the optical field to change, resulting in a slight, but detectable,
      shift in the resonance frequency of the device. Because the optical field
      circulates, it can interact many times with the environment, resulting in an
      inherent amplification of the signal, and very high sensitivities to minor
      changes in the environment. To perform targeted detection in complex
      environments, these platforms must be paired with a probe molecule (usually one
      half of a binding pair, e.g. antibodies/antigens) through surface modification.
      Although WGM optical resonators can be fabricated in several geometries from a
      variety of material systems, the silica microsphere is the most common. These
      microspheres are generally fabricated on the end of an optical fiber, which
      provides a "stem" by which the microspheres can be handled during
      functionalization and detection experiments. Silica surface chemistries may be
      applied to attach probe molecules to their surfaces; however, traditional
      techniques generated for planar substrates are often not adequate for these three
      dimensional structures, as any changes to the surface of the microspheres (dust,
      contamination, surface defects, and uneven coatings) can have severe, negative
      consequences on their detection capabilities. Here, we demonstrate a facile
      approach for the surface functionalization of silica microsphere WGM optical
      resonators using silane coupling agents to bridge the inorganic surface and the
      biological environment, by attaching biotin to the silica surface. Although we
      use silica microsphere WGM resonators as the sensor system in this report, the
      protocols are general and can be used to functionalize the surface of any silica
      device with biotin.

PMID- 22588225
TI  - Controlling the rate of electron transfer between a quantum dot and a tri
      ruthenium molecular cluster by tuning the chemistry of the interface.
AB  - Ultrafast transient absorption measurements reveal that the rate of photoinduced
      electron transfer (PET) from colloidal CdSe quantum dots (QDs) to oxo-centered
      triruthenium clusters (Ru(3)O) depends on the structure of the chemical headgroup
      by which the Ru(3)O clusters adsorb to the QDs. Complexes comprising QDs and
      Ru(3)O clusters adsorbed through a pyridine-4-carboxylic acid ligand (nic-Ru(3)O)
      have an intrinsic PET rate constant of (4.9 +/- 0.9) * 10(9) s(-1) whereas
      complexes comprising QDs and Ru(3)O clusters adsorbed through a 4
      mercaptopyridine ligand (thiol-Ru(3)O) have an intrinsic PET rate constant of (36
      +/- 7) * 10(9) s(-1). Cyclic voltammetry measurements of nic-Ru(3)O and thiol
      Ru(3)O yield reduction potentials vs. Ag/AgCl of -0.93 V for both clusters, and
      density functional theory calculations of the nic-Ru(3)O and thiol-Ru(3)O
      clusters yield internal reorganization energies for the cluster radical anion of 
      0.17 eV and -0.19 eV, respectively. The small differences in driving force and
      reorganization energy between the two complexes rule out these parameters as
      possible explanations for the factor-of-seven difference in the rate constants
      for PET. The difference in the observed rates of PET for the two complexes is
      therefore attributable to a difference in donor-acceptor electronic coupling,
      which, according to electronic structure calculations, is modulated by the
      torsional angle between the Ru(3)O core of the cluster and the functionalized
      pyridine ligand that bridges the cluster to the QD surface.

PMID- 22588226
TI  - Associations of physical activity and screen-time on health related quality of
      life in adults.
AB  - BACKGROUND: Associations between the combined effect of physical activity and
      screen based activities on health related quality of life remain largely
      undetermined. METHODS: During 2008-2010, cross-sectional data for self-reported
      health related quality of life, physical activity, and screen-time were collected
      for 3796 Australian adults. Logistic regression was conducted to examine
      associations for six combinations of physical activity (none, insufficient, and
      sufficient), and screen-time (low and high) on health related quality of life.
      RESULTS: In comparison to the reference category (sufficient physical activity
      and low screen-time) men and women who reported no physical activity and either
      high (OR=4.52, 95% CI 2.82-7.25) or low (OR=2.29, 95% CI 1.37-3.80) screen-time,
      were significantly more likely to report over 14 unhealthy days. Men reporting
      either; no physical activity and high (OR=3.15, 95% CI 1.92-5.15), or low
      (OR=2.17, 95% CI 1.30-3.63) screen-time; insufficient physical activity and high
      (OR=1.68, 95% CI 1.08-2.60), or low (OR=1.79, 95% CI 1.14-2.82) screen-time were
      more likely to rate their health as poor or fair. In women this was significant
      for those who reported no physical activity and high screen-time (OR=1.98, 95%
      CI, 1.19-3.31). CONCLUSIONS: Results suggest that the combination of no physical
      activity and high screen-time demonstrated the greatest negative impact on health
      related quality of life.

PMID- 22588228
TI  - Inequalities in usage of a public bicycle sharing scheme: socio-demographic
      predictors of uptake and usage of the London (UK) cycle hire scheme.
AB  - OBJECTIVE: Cycling confers individual and population-level health benefits, but
      uptake is not always equitable across socio-demographic groups. We sought to
      examine inequalities in uptake and usage of London's Barclays Cycle Hire (BCH)
      scheme. METHOD: We obtained complete BCH registration data, and compared users
      with the general population. We examined usage levels by explanatory variables
      including gender, small-area income-deprivation and local cycling prevalence.
      RESULTS: 100,801 registered individuals made 2.5 million trips between July 2010
      and March 2011. Compared with residents and workers in the central London area
      served by the scheme, registered individuals were more likely to be male and to
      live in areas of low deprivation and high cycling prevalence. Among those
      registered, females made 1.63 (95%CI 1.53, 1.74) fewer trips per month than
      males, and made under a fifth of all trips. Adjusting for the fact that deprived
      areas were less likely to be close to BCH docking stations, users in the most
      deprived areas made 0.85 (95%CI 0.63,1.07) more trips per month than those in the
      least deprived areas. CONCLUSION: Females and residents in deprived areas are
      underrepresented among users of London's public bicycle sharing scheme. The
      scheme's planned expansion into more deprived areas has, however, the potential
      to create a more equitable uptake of cycling.

PMID- 22588227
TI  - Making preventive medicine more personalized: implications for exercise-related
      research.
AB  - OBJECTIVE: This commentary offers a discussion of the need to consider behavioral
      interventions such as physical exercise as integral components of personalized
      medicine. METHODS: We discuss the concept of personalized medicine and review
      existing evidence of variability in response to exercise training. RESULTS: We
      argue that increased understanding is needed regarding sources of variability in
      exercise responsiveness, and that such understanding should lead to more
      tailored, often multimodal interventions. CONCLUSION: Studies of personalized
      medicine to date have primarily investigated heterogeneity in drug
      responsiveness; we believe it is time to begin considering preventive strategies
      such as exercise within a broader scope of personalized care.

PMID- 22588229
TI  - Encapsulation of angiogenic monocytes using bio-spraying technology.
AB  - Therapeutic neovascularisation using angiogenic cells has been hampered by the
      loss of cells from the target tissue. Encapsulation of these cells within a semi
      permeable membrane could improve their retention within the ischaemic tissue
      without affecting the excretion of the angiogenic growth factors produced. Bio
      spraying is a novel cell-handling technique that does not adversely affect cell
      viability. We used this technique to encapsulate human peripheral blood monocytes
      and found that cell viability, cell phenotype and functional downstream
      angiogenic signalling were preserved. Encapsulation of monocytes with macrophage
      colony stimulating factor resulted in increased vascular-endothelial growth
      factor production and enhanced angiogenic function. Bio-spraying/encapsulation
      has the potential to enhance the efficacy of current angiogenic cell therapy
      strategies and merits further investigation.

PMID- 22588230
TI  - Influence of trace elements in human tissue in low-energy photon brachytherapy
      dosimetry.
AB  - The aim of this paper is to determine the dosimetric impact of trace elements in
      human tissues for low-energy photon sources used in brachytherapy. Monte Carlo
      dose calculations were used to investigate the dosimetric effect of trace
      elements present in normal or cancerous human tissues. The effect of individual
      traces (atomic number Z = 11-30) was studied in soft tissue irradiated by low
      energy brachytherapy sources. Three other tissue types (prostate, adipose and
      mammary gland) were also simulated with varying trace concentrations to quantify
      the contribution of each trace to the dose distribution. The dose differences
      between cancerous and healthy prostate tissues were calculated in single- and
      multi-source geometries. The presence of traces in a tissue produces a difference
      in the dose distribution that is dependent on Z and the concentration of the
      trace. Low-Z traces (Na) have a negligible effect (<0.3%) in all tissues, while
      higher Z (K) had a larger effect (>3%). There is a potentially significant
      difference in the dose distribution between cancerous and healthy prostate
      tissues (4%) and even larger if compared to the trace-free composition (15%) in
      both single- and multi-sourced geometries. Trace elements have a non-negligible
      (up to 8% in prostate D(90)) effect on the dose in tissues irradiated with low
      energy photon sources. This study underlines the need for further investigation
      into accurate determination of the trace composition of tissues associated with
      low-energy brachytherapy. Alternatively, trace elements could be incorporated as
      a source of uncertainty in dose calculations.

PMID- 22588231
TI  - Screening, diagnosis, and treatment of dyslipidemia among persons with persistent
      mental illness: a literature review.
AB  - OBJECTIVE: Cardiovascular disease is the most frequent cause of death of persons
      with severe and persistent mental illness, and there is evidence of a widening
      mortality gap with the general population. Modifiable risk factors for
      cardiovascular disease, including dyslipidemia, are frequently underrecognized
      and undertreated. This review provides practitioners with an update on screening,
      diagnosis, and referral or treatment of dyslipidemia in this population. METHODS:
      A literature search in PubMed from 1990 to 2012 that used various combinations of
      the terms cholesterol, screening, diagnosis, treatment, and severe mental
      illnesses identified 74 clinically relevant articles for review, and reference
      lists guided further exploration of sources. Additional material was selected
      with a focus on emerging guidelines to create clinically relevant recommendations
      for practitioners. RESULTS: Multiple barriers can prevent clinicians from
      obtaining samples from fasting patients, which can be detrimental to successful
      screening. Dyslipidemia can be successfully screened for with nonfasting total
      cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides, with
      follow-up measurement of fasting low-density lipoprotein (LDL) cholesterol if
      total cholesterol is greater than 200 mg/dl or triglycerides are above 500 mg/dl.
      Compelling evidence supports pharmacologic treatment of dyslipidemia to reduce
      cardiovascular events among high-risk patients. CONCLUSIONS: When obtaining
      samples from fasting patients is not feasible, use of samples from nonfasting
      patients can radically improve management of dyslipidemia among persons with
      severe and persistent mental illness. Common medications used to treat
      dyslipidemia are inexpensive, safe, and effective and could be more liberally
      employed to address comorbidities in this population.

PMID- 22588234
TI  - Choice of ear for cochlear implantation in adults with monaural sound-deprivation
      and unilateral hearing aid.
AB  - OBJECTIVES: To identify whether speech recognition outcomes are influenced by the
      choice of ear for cochlear implantation in adults with bilateral hearing loss who
      use a hearing aid in 1 ear but have long-term auditory deprivation in the other.
      STUDY DESIGN: Retrospective matched cohort study. Speech recognition results were
      examined in 30 adults with monaural sound deprivation. Fifteen received the
      implant in the sound-deprived ear and 15 in the aided ear. SETTING: Tertiary
      referral centers with active cochlear implant programs. PATIENTS: Adults with
      bilateral hearing loss and a minimum of 15 years of monaural sound deprivation
      who received a cochlear implant after meeting the traditional implantation
      criteria of the referral centers. INTERVENTION: Cochlear implantation with
      devices approved by the U.S. Food and Drug Administration. MAIN OUTCOME
      MEASURE(S): Paired comparisons of postoperative monosyllabic word recognition
      scores obtained with the implant alone and in the usual listening condition (CI
      alone or bimodal). RESULTS: With the cochlear implant alone, individuals who
      received the implant in a sound-deprived ear obtained poorer scores than
      individuals who received the implant in the aided ear. There was no significant
      difference, however, in speech recognition results for the 2 groups when tested
      in their usual listening condition. In particular, poorer speech recognition
      scores were obtained with the cochlear implant alone by individuals using bimodal
      hearing. CONCLUSION: Similar clinical outcomes of cochlear implantation can be
      achieved by adults with a long-term monaural sound deprivation when comparing the
      usual listening condition, irrespective of whether the implant is in the sound
      deprived or in the aided ear.

PMID- 22588233
TI  - Benefit of a commercially available cochlear implant processor with dual
      microphone beamforming:  a multi-center study.
AB  - OBJECTIVE: Previous research shows that cochlear implant users experience
      significant difficulty with speech perception in noisy listening situations.
      There is a paucity of research evaluating the potential improvement in speech
      recognition in noise provided by a dual-microphone directional system in a
      commercial implant sound processor. The primary objective of this study was to
      compare speech recognition in quiet and in noise for the Nucleus Freedom and
      Nucleus 5 CP810 sound processors set to the manufacturer's default user programs
      for quiet and noisy environments. RESEARCH DESIGN: Crossover with repeated
      measures design. SETTING: This multi-center study was conducted across four
      cochlear implant clinics in the United States. PATIENTS: Thirty-five adults with
      unilateral Nucleus Freedom cochlear implants. All subjects had used their
      cochlear implant for at least 6 months and had substantial open-set word
      recognition as evidenced by a score of at least 40% correct on the Consonant
      Nucleus-Consonant (CNC) monosyllabic word recognition test in quiet.
      INTERVENTION: All subjects (previous users of the Nucleus Freedom sound
      processor) were fitted with the Nucleus 5 sound processor. Performance was
      assessed while these subjects used each sound processor in the default user
      program the manufacturer recommends for quiet and noisy conditions. MAIN OUTCOME
      MEASURES: Speech recognition was assessed with CNC monosyllabic words in quiet
      and sentences in noise from the BKB-SIN (Bamford-Kowal-Bench Sentences in Noise)
      test. The data were analyzed with descriptive statistics and performance with
      each processor in each listening condition was compared using a repeated-measures
      analysis of variance. RESULTS: Word recognition in quiet was significantly better
      with the Nucleus 5 sound processor when compared to performance with the Nucleus
      Freedom processor. In noise, the Nucleus 5 sound processor also provided a
      significant improvement in speech recognition relative to the performance with
      the Nucleus Freedom. CONCLUSION: The results of the study suggest that the
      Nucleus 5 sound processor provides significantly better speech recognition in
      quiet and in noise when compared with performance with the Nucleus Freedom
      processor.

PMID- 22588232
TI  - Timing of cochlear implantation and parents' global ratings of children's health
      and development.
AB  - OBJECTIVE: To assess children's health-related quality of life (HRQL) and
      development after cochlear implant (CI) surgery and compare improvements between
      different age of implantation categories. STUDY DESIGN: Prospective, longitudinal
      study comparing outcomes of deaf children post-CI with hearing controls. SETTING:
      Six US CI centers. PATIENTS: Deaf children who received CI (n = 188) and hearing
      children of comparable ages (n = 97). INTERVENTION: CI before 5 years of age.
      MAIN OUTCOME MEASURE: Parental ratings of global HRQL and development, as
      assessed over the first 4 years of follow-up using visual analog scales.
      Development scores assess parental views of children's growth and development,
      motor skills, ability to express themselves and communicate with others, and
      learning abilities. Associations of baseline child and family characteristics
      with post-CI HRQL and development were investigated using multivariable analysis,
      controlling for factors that influence post-CI language learning. RESULTS:
      Baseline deficits of CI candidates relative to hearing controls were larger in
      development than HRQL. Development scores improved significantly by 4 years after
      CI, particularly in the youngest CI recipients. Developmental deficits of older
      CI recipients with early, extended hearing aid use were only partially remediated
      by CI. Overall, no significant health deficits were observed in CI children after
      4 years. Cognition and speech recognition were positively associated with both
      HRQL and development. CONCLUSION: Parental perspectives on quality of their
      child's life and development provide practical insight into the optimal timing of
      interventions for early-onset deafness. Validity of parental global assessments
      is supported by clinical measures of speech perception and language learning and
      comparison with a well-validated health status instrument.

PMID- 22588235
TI  - Cholesteatoma-associated pathogenicity:  potential role of lysosomal
      exoglycosidases.
AB  - The enzymatic profile of lysosomal exoglycosidases in middle ear cholesteatoma
      has not been well known. The assessment of glycoconjugate catabolism may
      contribute to a better understanding of cholesteatoma pathogenesis. OBJECTIVE:
      The study aim was to evaluate catabolic processes of glycoproteins, glycolipids,
      and proteoglycans in cholesteatoma through outlining the concentration of N
      acetyl-beta-hexosaminidase (HEX), beta-glucuronidase (GLUC), and beta
      galactosidase (GAL) activity as well as in serum of cholesteatoma patients and
      healthy volunteers. STUDY DESIGN: Acquired cholesteatomas (n = 25) and normal
      retroauricular skin specimens (n = 25) were taken during surgery as well as serum
      from cholesteatoma patients and healthy volunteers. HEX, GAL, and GLUC activity
      was assessed on basis of p-nitrophenol release from derivatives of the substrate
      (HEX: N-acetylglucosamine i N-acetylgalactosamine, GAL from galactose, and GLUC
      from glucuronide). RESULTS: The mean concentration of activity of HEX 1142.39
      pKat/ml, GAL 8.90 pKat/ml, and GLUC 14.06 pKat/ml was significantly higher
      compared with the concentration of enzyme activity in normal tissue: HEX 267.65
      pKat/ml, GAL 3.44 pKat/ml, and GLUC 3.90 pKat/ml. In the serum of cholesteatoma
      patients, the mean concentration of enzyme activities were as follows: HEX 641.62
      pKat/ml, GAL 4.55 pKat/ml, and GLUC 12.80 pKat/ml and were significantly higher
      compared with the concentration of HEX activity (215.75 pKat/ml), GAL (1.89
      pKat/ml), and GLUC (5.51 pKat/ml) in the serum of the healthy control group. In
      cholesteatoma compared with the normal tissue, there is an increase of the
      glycoconjugate catabolism due to significantly higher concentration of HEX, GAL,
      and GLUC activity in cholesteatoma. Cholesteatoma causes systemic reaction due to
      the increase of HEX, GAL, and GLUC activity in patient serum.

PMID- 22588236
TI  - Usefulness of cortical mastoidectomy in myringoplasty.
AB  - OBJECTIVES: The usefulness of cortical mastoidectomy in myringoplasty remains an
      issue of controversy. We aimed to assess the effectiveness of mastoidectomy on
      outcomes of tympanoplasty performed in patients with persistent or intermittent
      discharging chronic suppurative otitis media without cholesteatoma. STUDY DESIGN:
      Prospective, randomized, single-blinded study. Level of evidence-1B. SETTING:
      Tertiary referral center. PATIENTS: Three hundred twenty consecutive adult
      patients presenting persistent or intermittent otorrhea during the preceding 6
      months scheduled for myringoplasty were included. INTERVENTIONS: Patients were
      randomly assigned to undergo either myringoplasty with cortical mastoidectomy
      (Group A) or myringoplasty only (Group B). MAIN OUTCOME MEASURES: Graft success
      rate and mean postoperative air-bone gap. Auditory outcomes were evaluated at one
      year postoperatively. RESULTS: At the end of the follow-up period, there were 24
      failures within Group A (success rate, 82.8%) and 34 within Group B (success
      rate, 76%), statistically not significant. In the univariate analysis, 3 factors
      were found to be significant in predicting success rate: healthy opposite ear, a
      long dry period preceding the operation and nonsmoker status. The only factor
      attaining significance in the multivariate analysis was a dry period longer than
      3 months. CONCLUSION: Cortical mastoidectomy offers no additional benefit in
      myringoplasty performed on patients with persistent or intermittent discharging
      CSOM and no evidence of cholesteatoma or mucosal blockage within the antrum.

PMID- 22588237
TI  - Petrous bone fracture:  a virtual trauma analysis.
AB  - OBJECTIVE: The temporal bone shields sensorineural, nervous, and vascular
      structures explaining the potential severity and complications of trauma related
      to road and sport accidents. So far, no clear data are available on the exact
      mechanisms involved for fracture processes. Modelization of structures helps to
      answer these concerns. Our objective was to design a finite element model of the
      petrous bone structure to modelize temporal bone fracture propagation in a
      scenario of lateral impact. MATERIALS AND METHODS: A finite element model of the
      petrous bone structure was designed based on computed tomography data. A 7-m/s
      lateral impact was simulated to reproduce a typical lateral trauma. Results of
      model analysis was based on force recorded, stress level on bone structure up to
      induce a solution of continuity of the bony structure. RESULTS: Model simulation
      showed that bone fractures follow the main axes of the petrous bone and occurred
      in a 2-step process: first, a crush, and second, a massive fissuration of the
      petrous bone. The lines of fracture obtained by simulation of a lateral impact
      converge toward the middle ear region. This longitudinal fracture is located at
      the mastoid-petrous pyramid junction. DISCUSSION: Using this model, it was
      possible to map petrous bone fractures including fracture chronology and areas of
      fusion of the middle ear region. This technique may represent a first step to
      investigate the pathophysiology of the petrous bone fractures, aiming to define
      prognostic criteria for patients' care.

PMID- 22588238
TI  - Dexamethasone levels and base-to-apex concentration gradients in the scala
      tympani perilymph after intracochlear delivery in the guinea pig.
AB  - HYPOTHESIS: To determine whether intracochlearly applied dexamethasone will lead
      to better control of drug levels, higher peak concentrations, and lower base-to
      apex concentration gradients in the scala tympani (ST) of the guinea pig than
      after intratympanic (round window [RW]) application. BACKGROUND: Local
      application of drugs to the RW results in substantial variation of intracochlear
      drug levels and significant base-to-apex concentration gradients in ST. METHODS:
      Two microliters of dexamethasone-phosphate (10 mg/ml) were injected into ST
      either through the RW membrane, which was covered with 1% sodium hyaluronate gel
      or through a cochleostomy with a fluid tight seal of the micropipette. Perilymph
      was sequentially sampled from the apex at a single time point for each animal, at
      20, 80, or 200 min after the injection ended. Results were mathematically
      interpreted by means of an established computer model and compared with previous
      experiments performed by our group with the same experimental techniques but
      using intratympanic applications. RESULTS: Single intracochlear injections of 20
      minutes resulted in approximately 10 times higher peak concentrations (on
      average) than 2 to 3 hours of intratympanic application to the RW niche.
      Intracochlear drug levels were less variable and could be measured for over 220
      minutes. Concentration gradients along the scala tympani were less pronounced.
      The remaining variability in intracochlear drug levels was attributable to
      perilymph and drug leak from the injection site. CONCLUSION: With significantly
      higher, less variable drug levels and smaller base-to-apex concentration
      gradients, intracochlear applications have advantages to intratympanic
      injections. For further development of this technique, it is of importance to
      control leaks of perilymph and drug from the injection site and to evaluate its
      clinical feasibility and associated risks.

PMID- 22588239
TI  - Trauma care and case fatality during a period of frequent, violent terror attacks
      and thereafter.
AB  - BACKGROUND: From September 1999 through January 2004 during the second Intifada
      (al-Aqsa), there were frequent terror attacks in Jerusalem. We assessed the
      effects on case fatality of introducing a specialized, intensified approach to
      trauma care at the Hebrew University-Hadassah Hospital Shock Trauma Unit (HHSTU)
      and other level I Israeli trauma units. This approach included close senior
      supervision of prehospital triage, transport, and all surgical procedures and
      longer hospital stays despite high patient-staff ratios and low hospital budgets.
      Care for lower income patients also was subsidized. METHODS: We tracked case
      fatality rates (CFRs) initially during a period of terror attacks (1999-2003) in
      8,127 patients (190 deaths) at HHSTU in subgroups categorized by age, injury
      circumstances, and injury severity scores (ISSs). Our comparisons were four other
      Israeli level I trauma centers (n = 2,000 patients), and 51 level I U.S. trauma
      centers (n = 265,902 patients; 15,237 deaths). Detailed HHSTU follow-up continued
      to 2010. RESULTS: Five-year HHSTU CFR (2.62 %) was less than half that in 51 U.S.
      centers (5.73 %). CFR progressively decreased; in contrast to a rising trend in
      the US for all age groups, injury types, and ISS groupings, including gunshot
      wounds (GSW). Patients with ISS > 25 accounted for 170 (89 %) of the 190 deaths
      in HHSTU. Forty-one lives were saved notionally based on U.S. CFRs within this
      group. However, far more lives were saved from reductions in low CFRs in large
      numbers of patients with ISS < 25. CFRs in HHSTU and other Israeli trauma units
      decreased more through the decade to 1.9 % up to 2010. CONCLUSIONS: Sustained
      reductions in trauma unit CFRs followed introduction of a specialized,
      intensified approach to trauma care.

PMID- 22588241
TI  - Control of splenic bleeding during splenic flexure mobilisation by
      devascularisation of the inferior pole of the spleen.
AB  - Injury to the spleen is a recognised complication of colorectal resections
      involving mobilisation of the splenic flexure. Bleeding from the spleen is
      difficult to control and not infrequently requires splenectomy with its attendant
      lifelong potential haematological and immunological complications. Furthermore,
      conversion from a laparoscopic to an open procedure may be required as splenic
      haemorrhage is more difficult to control laparoscopically. We describe a
      technique for control of bleeding from the inferior pole of the spleen, used
      during laparoscopic splenectomy, which may be applied to either open or
      laparoscopic surgery to achieve haemostasis thereby obviating splenectomy and in
      laparoscopic cases, conversion to open.

PMID- 22588242
TI  - Coated transjugular intrahepatic portosystemic shunt does not improve
      thrombocytopenia in patients with liver cirrhosis.
AB  - BACKGROUND/AIM: Thrombocytopenia is a common complication of chronic liver
      disease. The theory of portal decompression to improve thrombocytopenia due to
      hypersplenism has led to the study of transjugular intrahepatic portosystemic
      shunt (TIPS) as a potential therapy. However, there is a paucity of data and
      results have been conflicting. The aim of this study was to determine whether
      platelet counts improved in cirrhotic patients after placement of the new
      polytetrafluoroethylene (PTFE)-coated TIPS, developed in 2004. METHODS: This is a
      retrospective cohort study of 68 patients with chronic liver disease who
      underwent a TIPS procedure. One-hundred twenty controls who did not undergo a
      TIPS procedure were matched on average for age, sex, race, model for end-stage
      liver disease (MELD) score, and etiology of liver disease. Platelet and
      hemoglobin counts were recorded during the month prior to the TIPS procedure
      (baseline) and over the following 12-14 months or until transplanted or death.
      RESULTS: While platelet counts improved during the first 3 months after TIPS with
      a mean increase of 11.25 * 103/MUL (p = 0.064), they returned to baseline (pre
      TIPS) with mean platelets of 91.31 * 103 MUL by 12-14 months in comparison with a
      mild decrease of 10.2 * 103 MUL in platelet counts in the control group from
      100.4 * 103 MUL to 90.2 * 103 (p = 0.119). There was also no significant
      correlation between platelet counts and etiology of liver disease, age, race,
      gender, or MELD score. Hemoglobin counts were found to have a small increase of
      0.657 g/dL over the 12-14 month course in the TIPS group, which was statistically
      significant (p = 0.003). CONCLUSION: There does not appear to be a significant
      improvement in thrombocytopenia in cirrhotic patients after TIPS placement,
      despite advances in TIPS stents. However, there may be a mild improvement in
      anemia after TIPS implantation.

PMID- 22588243
TI  - Prevalence of autoimmune pancreatitis and other benign disorders in
      pancreatoduodenectomy for presumed malignancy of the pancreatic head.
AB  - BACKGROUND: Occasionally patients undergoing resection for presumed malignancy of
      the pancreatic head are diagnosed postoperatively with benign disease. Autoimmune
      pancreatitis (AIP) is a rare disease that mimics pancreatic cancer. We aimed to
      determine the prevalence of benign disease and AIP in patients who underwent
      pancreatoduodenectomy (PD) over a 9-year period, and to explore if and how
      surgery could have been avoided. METHODS: All patients undergoing PD between 2000
      and 2009 in a tertiary referral centre were analyzed retrospectively. In cancer
      negative cases, postoperative diagnosis was reassessed. Preoperative index of
      suspicion of malignancy was scored as non-specific, suggestive, or high. In AIP
      patients, diagnostic criteria systems were checked. RESULTS: A total of 274 PDs
      were performed for presumed malignancy. The prevalence of benign disease was 8.4
      %, overall prevalence of AIP was 2.6 %. Based on preoperative index of suspicion
      of malignancy, surgery could have been avoided in 3 non-AIP patients. All AIP
      patients had sufficient index to justify surgery. If diagnostic criteria would
      have been checked; however, surgery could have been avoided in one to five AIP
      patients. CONCLUSIONS: The prevalence of benign disease in patients who underwent
      PD for presumed malignancy was 8.4 %, nearly one-third attributable to AIP.
      Although misdiagnosis of AIP as carcinoma is a problem of limited quantitative
      importance, every effort to establish the correct diagnosis should be undertaken
      considering the major therapeutic consequences. IgG4 measurement and systematic
      use of diagnostic criteria systems are recommended for every candidate patient
      for PD when there is no histological proof of malignancy.

PMID- 22588245
TI  - Comparison of subjective olfaction ratings in patients with and without olfactory
      disorders.
AB  - OBJECTIVE: Olfactory dysfunction is common. The reliability of self-assessment
      tools for smell testing is still controversial. This study aimed to provide new
      data about the accuracy of olfactory self-assessment compared with a standardised
      smell test. DESIGN: Prospective, controlled, cohort study of patients with
      olfactory disorders and healthy controls. SUBJECTS: Ninety-six patients with a
      smell deficit and 71 controls were asked to rate their sense of smell on a visual
      analogue scale. Their olfactory abilities were also evaluated with the Sniffin'
      Sticks tests. RESULTS: The whole cohort showed a significant correlation between
      visual analogue scale smell scores and Sniffin' Sticks total scores. This
      correlation was also significant in the patient group, but not in the control
      group. These results were independent of olfactory deficit aetiology and subject
      age. CONCLUSION: Self-assessment of olfaction is only a reliable indicator in
      smell-impaired patients, not in healthy controls. For an accurate assessment of
      olfaction, reliable, standardised tests are needed.

PMID- 22588244
TI  - Soluble epoxide hydrolase gene deficiency or inhibition attenuates chronic active
      inflammatory bowel disease in IL-10(-/-) mice.
AB  - BACKGROUND: Soluble epoxide hydrolase (sEH) metabolizes anti-inflammatory
      epoxyeicosatrienoic acids (EETs) into their much less active dihydroxy
      derivatives dihydroxyeicosatrienoic acids. Thus, targeting sEH would be important
      for inflammation. AIMS: To determine whether knockout or inhibition of sEH would
      attenuate the development of inflammatory bowel disease (IBD) in a mouse model of
      IBD in IL-10(-/-) mice. METHODS: Either the small molecule sEH inhibitor trans/-4
      [4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB) or sEH knockout
      mice were used in combination with IL-10(-/-) mice. t-AUCB was administered to
      mice in drinking fluid. Extensive histopathologic, immunochemical, and
      biochemical analyses were performed to evaluate effect of sEH inhibition or
      deficiency on chronic active inflammation and related mechanism in the bowel.
      RESULTS: Compared to IL-10 (-/-) mice, sEH inhibition or sEH deficiency in IL-10(
      /-) mice resulted in significantly lower incidence of active ulcer formation and
      transmural inflammation, along with a significant decrease in myeloperoxidase
      labeled neutrophil infiltration in the inflamed bowel. The levels of IFN-gamma,
      TNF-alpha, and MCP-1, as well VCAM-1 and NF-kB/IKK-alpha signals were
      significantly decreased as compared to control animals. Moreover, an eicosanoid
      profile analysis revealed a significant increase in the ratio of EETs/DHET and
      EpOME/DiOME, and a slightly down-regulation of inflammatory mediators LTB(4) and
      5-HETE. CONCLUSION: These results indicate that sEH gene deficiency or inhibition
      reduces inflammatory activities in the IL-10 (-/-) mouse model of IBD, and that
      sEH inhibitor could be a highly potential in the treatment of IBD.

PMID- 22588247
TI  - Unique biocatalytic resolution of racemic tetrahydroberberrubine via kinetic
      glycosylation and enantio-selective sulfation.
AB  - In this communication, we document a facile kinetic glycosylation resolution of
      racemic tetrahydroberberrubine. We also demonstrate that the enantiomeric excess
      of the resolved products is increased via a second resolution of the minor
      product of the first glycosylation resolution. This provides a rare example of
      tandem kinetic resolution of racemates.

PMID- 22588246
TI  - Sequential immunological analysis of HBV/HCV co-infected patients during Peg
      IFN/RBV therapy.
AB  - BACKGROUND: The immunopathogenesis of dual chronic infection with hepatitis B
      virus and hepatitis C virus (HBV/HCV) remains unclear. The in vivo suppressive
      effects of each virus on the other have been reported. In this study we aimed to
      analyze the virological and immunological parameters of HBV/HCV coinfected
      patients during pegylated interferon/ribavirin (Peg-IFN/RBV) therapy. METHODS:
      One patient with high HBV-DNA and high HCV-RNA titers (HBV-high/HCV-high) and 5
      patients with low HBV-DNA and high HCV-RNA titers (HBV-low/HCV-high) were
      enrolled. Twenty patients monoinfected with HBV and 10 patients monoinfected with
      HCV were enrolled as control subjects.. In vitro cultures of Huh 7 cells with
      HBV/HCV dual infection were used to analyze the direct interaction of HBV/HCV.
      RESULTS: Direct interaction of HBV clones and HCV could not be detected in the
      Huh-7 cells. In the HBV-high/HCV-high-patient, the HCV-RNA level gradually
      declined and HBV-DNA gradually increased during Peg-IFN/RBV therapy. Activated
      CD4- and CD8-positive T cells were increased at 1 month of Peg-IFN/RBV-therapy,
      but HBV-specific IFN-gamma-secreting cells were not increased and HBV-specific
      interleukin (IL)-10 secreting cells were increased. The level of HBV- and HCV
      specific IFN-gamma-secreting cells in the HBV-high/HCV-high-patient was low in
      comparison to that in the HBV- or HCV-monoinfected patients. In the HBV-low/HCV
      high-patient, HCV-RNA and HBV-DNA rapidly declined during Peg-IFN/RBV therapy.
      Activated CD4- and CD8-positive T cells were increased, and HBV- and HCV-specific
      IFN-gamma-secreting cells were also increased during Peg-IFN/RBV-therapy.
      CONCLUSION: The immunological responses of the HBV-high/HCV-high patient were low
      in comparison to the responses in HBV and HCV monoinfected patients. Moreover,
      the response of immune cells in the HBV-high/HCV-high patient during Peg-IFN/RBV
      therapy was insufficient to suppress HBV and HCV.

PMID- 22588248
TI  - 'Our community is the worst': the influence of cultural beliefs on stigma,
      relationships with family and help-seeking in three ethnic communities in London.
AB  - BACKGROUND: Existing knowledge about the cultural beliefs of black and minority
      ethnic (BME) communities in the UK regarding stigma and mental illness is
      limited. MATERIAL: Data were collected in 10 focus groups, five with service
      users and five with laypersons, from BME communities in London. DISCUSSION:
      Thematic analysis identified that cultural beliefs regarding mental illness
      reflect four different voices present within the BME communities. CONCLUSION: The
      study revealed that cultural beliefs influencing both relationships with family
      and, consequently, help-seeking for individuals with mental illness must be
      considered in the development of anti-stigma interventions and when engaging
      communities around mental health.

PMID- 22588249
TI  - Charge dynamics in solar cells with a blend of pi-conjugated polymer-fullerene
      studied by transient photo-generated voltage.
AB  - The biphasic feature of transient photo-generated voltage (TPV) is investigated
      in organic solar cells (OSCs) with a blend active layer of poly(3-hexylthiophene)
      (P3HT) and phenyl C61 butyric acid methyl ester (PCBM). The positive and negative
      components in biphasic TPV are explained through PCBM only and P3HT only devices.
      The negative and positive components are ascribed to the dipole formation at the
      buried interface of P3HT/indium tin oxide (ITO) and PCBM/ITO respectively. Based
      on these findings, two fundamental phenomena are revealed as follows: (1)
      interfacial modification on the buried interface inverts the negative component
      in biphasic TPV to a positive component, which prevents the leakage current
      channel in the conventional OSC structure; and (2) the solvent chosen transforms
      the positive component in biphasic TPV into a negative signal, which blocks the
      leakage current channel in the inverted OSC structure. Consequently, the study of
      TPV polarity provides the justification of the interaction at the buried
      interface. Besides, the decay of TPV is found to be bi-exponential, which can be
      used as a tool to estimate the degree of charge balance in OSCs.

PMID- 22588251
TI  - Peer influences on drug self-administration: social facilitation and social
      inhibition of cocaine intake in male rats.
AB  - RATIONALE: One problem facing animal models of intravenous drug self
      administration, particularly those examining social manipulations, is that
      subjects must be removed from the home environment and separated from cagemates
      during testing. This represents a limitation of animal models because it fails to
      capture the complex social environments in which drug use often occur.
      OBJECTIVES: The aim of this study was to examine intravenous cocaine self
      administration in isolated and socially housed rats, with the caveat that the
      socially housed subjects lived together 24 h/day, including during daily self
      administration sessions. As a secondary aim, the study examined the impact of a
      companion that also self-administered cocaine versus a companion without access
      to cocaine. METHODS: Male rats were obtained at weaning and reared in isolated or
      pair-housed conditions for 6 weeks. Rats were then implanted with intravenous
      catheters and transferred to custom-built operant conditioning chambers that
      served as home cages for the remainder of the study. For some socially housed
      subjects, both rats had simultaneous access to cocaine; for others, only one rat
      of the pair had access to cocaine. RESULTS: Cocaine self-administration was
      facilitated in socially housed rats if both members of the pair had access to
      cocaine; however, cocaine self-administration was inhibited if only one rat of
      the pair had access to cocaine. CONCLUSIONS: These data indicate that the self
      administration behavior of a peer, not merely the presence of a peer, determines
      whether cocaine self-administration is facilitated or inhibited by social
      contact.

PMID- 22588250
TI  - NMDA receptor antagonism: escalation of aggressive behavior in alcohol-drinking
      mice.
AB  - RATIONALE: Memantine is a potential treatment for alcoholic patients, yet few
      studies investigate the effect of concurrent treatment with memantine and ethanol
      on aggression. We evaluated aggressive behavior following ethanol consumption and
      treatment with glutamatergic drugs to characterize interactions between these
      compounds. OBJECTIVE: This study aimed to use rodent models of aggression to
      examine interactions between glutamatergic compounds and ethanol. MATERIALS AND
      METHODS: Once male CFW mice reliably self-administered 1 g/kg ethanol or water,
      they were assessed for aggression in resident-intruder confrontations.
      Alternatively, aggression was evaluated following a social-instigation procedure.
      Animals were then injected with memantine, ketamine, neramexane, MTEP, or
      LY379268 before aggressive confrontations. Effects of the pharmacological
      manipulations on salient aggressive and non-aggressive behaviors were analyzed.
      RESULTS: Moderate doses of memantine, neramexane, and MTEP interacted with
      ethanol to increase the frequency of attack bites while ketamine did not. The
      highest dose of LY379268, an mGluR(2/3) agonist, reduced both aggressive and non
      aggressive behaviors after water and ethanol self-administration. Attack bites
      increased with social instigation and decreased with administration of high doses
      of MTEP and LY379268. Memantine and MTEP both reduced attack bite frequency in
      the instigation condition without reducing locomotor behavior. CONCLUSIONS:
      Memantine and neramexane interacted with ethanol to heighten aggression. The
      binding characteristics of these compounds allow for 'partial trapping' by which
      some NMDARs are unblocked between depolarizations. We propose that this feature
      may contribute to the differential aggression-heightening interactions between
      these compounds and ethanol. MTEP also interacted with ethanol to escalate
      aggression, possibly through inhibition of mGluR(5) modulation of NMDARs.

PMID- 22588252
TI  - The effect of morphine dependence on impulsive choice in rats.
AB  - RATIONALE: In the human opiate-dependent population, the most consistently
      reported deficit in executive functioning is impulsivity. Previous research has
      shown that acute and chronic exposure to drugs of abuse can increase impulsive
      choice; however, the extent to which opiate dependence contributes to increased
      impulsivity has not been examined. We report here the effects of morphine
      dependence on rats' delay discounting (DD) of a sucrose reward. METHODS: We
      assigned rats randomly to either a dependent group that received a nightly 30
      mg/kg subcutaneous dose of morphine or a morphine-naive group that received a
      nightly saline injection. DD of a sucrose reward was examined in rats prior to
      initiation of the dosing regimen, 22.5 h after the daily maintenance dose, and
      after a 14-day abstinence period. RESULTS: The groups did not differ at baseline,
      but rats showed accelerated DD while dependent on morphine. After withdrawal from
      morphine, DD in previously dependent rats was not significantly different from
      that of naive rats. Since dependent rats also showed reduced motivation to
      acquire the sucrose reinforcer, we performed a separate experiment to test
      whether such a decrease in motivation could cause an increase in impulsivity. We
      found that food-deprived rats switched to a free-feeding diet did not differ in
      DD from rats maintained at 85 % of free-feeding weight. CONCLUSIONS: An increase
      in impulsivity can result from physical dependence on morphine and cannot be
      attributed to changes in motivation to acquire sucrose-reinforced responses.

PMID- 22588253
TI  - Balanced placebo design with marijuana: pharmacological and expectancy effects on
      impulsivity and risk taking.
AB  - RATIONALE: Marijuana is believed to increase impulsivity and risk taking, but the
      processes whereby it affects such behaviors are not understood. Indeed, either
      the pharmacologic effect of delta-9-tetrahydrocannabinol (THC) or the expectancy
      of receiving it may lead to deficits in cognitive processing and increases in
      risk taking. OBJECTIVES AND METHODS: We examined the relative effects of
      expecting to receive active marijuana and the pharmacological drug effects using
      a balanced placebo design. Young adult regular marijuana users (N = 136) were
      randomly assigned into one of four groups in a two * two instructional set (Told
      THC vs. Told no THC) by drug administration (smoked marijuana with 2.8 % THC vs.
      placebo) design. Dependent measures included subjective intoxication, behavioral
      impulsivity, and decision-making related to risky behaviors. RESULTS: Active THC,
      regardless of expectancy, impaired inhibition on the Stop Signal and Stroop Color
      Word tasks. Expectancy of having smoked THC, regardless of active drug, decreased
      impulsive decision-making on a delay discounting task among participants
      reporting no deception and increased perception of sexual risk among women,
      consistent with a compensatory effect. Expectancy of smoking THC in combination
      with active THC increased negative perceptions from risky alcohol use. Active
      drug and expectancy independently increased subjective intoxication. CONCLUSIONS:
      Results highlight the importance of marijuana expectancy effects as users
      believing they are smoking marijuana may compensate for expected intoxication
      effects when engaged in deliberate decision-making by making less impulsive and
      risky decisions. Effects of marijuana on impulsive disinhibition, by contrast,
      reflect direct pharmacologic effects for which participants did not compensate.

PMID- 22588254
TI  - Clinical and imaging features of the room tilt illusion.
AB  - Room tilt illusion (RTI) is a transient disorder of the environmental visuo
      spatial perception consisting of paroxysmal tilts of the visual scene. It is
      attributed to an erroneous cortical mismatch of the visual and vestibular three
      dimensional coordinate maps. Thirteen subjects were included in this
      retrospective case series. Clinical presentation was 180o rotation of the visual
      scene following the coronal plane in seven patients. The most common cause for
      RTI in our series was posterior circulation ischaemia (five cases). Cases of
      endolymphatic sac tumour, critical illness neuropathy, acute traumatic myelopathy
      and multiple system atrophy causing RTI are reported for the first time. No case
      of supratentorial focal lesion was found. In order to describe the clinical and
      imaging features of RTI, 135 cases previously reported in the literature were
      reviewed along with our series. There was a male predominance (60.2 %). Mean age
      was 51.2 +/- 20.3 years. The most common location of the injury was the central
      nervous system (CNS) (61.4 %). Supratentorial and infratentorial structures
      accounted for the same frequency of lesions. The most common aetiology was
      cerebral ischaemia (infarction or transient ischaemic episode; 27.7 %). These
      patients were significantly older and their lesions commonly involved posterior
      fossa structures when compared to patients with non-vascular disorders. In
      summary, RTI is a manifestation of several CNS and vestibular disorders, and
      rarely of peripheral nervous system disorders, triggered by disruption of
      vestibular and sensory perception or integration. Cerebral ischaemic disorders
      are the most common aetiology for this rare syndrome.

PMID- 22588256
TI  - A novel, orally active alpha 4 integrin antagonist, AJM300 prevents the
      development of experimental colitis induced by adoptive transfer of IL-10
      deficient CD4(+) T cells in mice.

PMID- 22588255
TI  - Vitamin D levels in Hispanics with multiple sclerosis.
AB  - Vitamin D has been associated with multiple sclerosis (MS) and several markers of
      disease state in whites. There are limited reports of vitamin D's influence in MS
      in ethnic groups, such as in Hispanics. In this study, we compared vitamin D
      levels in Hispanics and whites with MS and tried to determine whether season or
      increasing disability influence hypovitaminosis D in Hispanics with MS. Serum 25
      hydroxyvitamin D [25(OH)D] levels and clinical characteristics were compared in a
      cross-sectional sample of Hispanics (n = 80) and whites (n = 80) with MS
      recruited from the University of Southern California. Serum 25(OH)D levels were
      significantly lower in Hispanics than whites with MS (mean and standard deviation
      25.1 +/- 9.4 and 37.3 +/- 19.8 ng/ml, respectively; p < 0.001). Hispanics were
      significantly more likely than whites to be vitamin D insufficient (<= 30 ng/ml;
      70 vs. 41 %, respectively; p < 0.001) and deficient (<= 20 ng/ml; 40 vs. 14 %,
      respectively, p < 0.001). In Hispanics, serum 25(OH)D levels were not influenced
      by season (p = 0.8) or higher physical disability (EDSS >= 6, p = 0.7). We found
      that the relationship between vitamin D and MS differs by Hispanic ethnicity.
      Hypovitaminosis D was significantly more common among Hispanics than among whites
      with MS, and the majority of Hispanics were vitamin D insufficient.
      Interestingly, there was no association between vitamin D levels and season or
      increasing disability in the Hispanics. Our findings imply that factors
      influencing vitamin D levels and possibly vitamin D requirements may vary by
      ethnicity in patients with MS. These results should be confirmed in larger,
      prospective multi-ethnic cohort studies.

PMID- 22588257
TI  - Involvement of inositol 1,4,5-trisphosphate formation in the voltage-dependent
      regulation of the Ca(2+) concentration in porcine coronary arterial smooth muscle
      cells.
AB  - The involvement of inositol 1,4,5-trisphosphate (IP(3)) formation in the voltage
      dependent regulation of intracellular Ca(2+) concentration ([Ca(2+)](i)) was
      examined in smooth muscle cells of the porcine coronary artery. Slow ramp
      depolarization from -90 to 0 mV induced progressive [Ca(2+)](i) increase. The
      slope was reduced or increased in the presence of Cd(2+) or (+/-)-1,4-dihydro-2,6
      dimethyl-5-nitro-4-(2-[trifluoromethyl]-phenyl)pyridine-3-carboxlic acid methyl
      ester (Bay K 8644), respectively. The decrease in [Ca(2+)](i) via the membrane
      hyperpolarization induced by K(+) channel openers (levcromakalim and Evans blue)
      under current clamp was identical to that under voltage clamp. The step
      hyperpolarization from -40 to -80 mV reduced [Ca(2+)](i) uniformly over the whole
      cell area with a time constant of ~10 s. The [Ca(2+)](i) at either potential was
      unaffected by heparin, an inhibitor of IP(3) receptors. Alternatively,
      [Ca(2+)](i) rapidly increased in the peripheral regions by depolarization from 
      80 to 0 mV and stayed at that level (~400 nM) during a 60-s pulse. When the
      pipette solution contained IP(3) pathway blockers [heparin, 2
      aminoethoxydiphenylborate, xestospongin C, or 1-[6-[((17beta)-3-methoxyestra
      1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dione (U73122)], the peak
      [Ca(2+)](i) was unchanged, but the sustained [Ca(2+)](i) was gradually reduced by
      ~250 nM within 30 s. In the presence of Cd(2+), a long depolarization period
      slightly increased the [Ca(2+)](i), which was lower than that in the presence of
      heparin alone. In coronary arterial myocytes, the sustained increase in the
      [Ca(2+)](i) during depolarization was partly caused by the Ca(2+) release
      mediated by the enhanced formation of IP(3). The initial [Ca(2+)](i) elevation
      triggered by the Ca(2+) influx though voltage-dependent Ca(2+) channels may be
      predominantly responsible for the activation of phospholipase C for IP(3)
      formation.

PMID- 22588258
TI  - Pharmacological characterization of (3S)-3-(hydroxymethyl)-4-(5-methylpyridin-2
      yl)-N-[6-(2,2,2-trifluoroethoxy)pyridin-3-yl]-3,4-dihydro-2H-benzo[b][1,4]oxazine
      8-carboxamide (JTS-653), a novel transient receptor potential vanilloid 1
      antagonist.
AB  - Transient receptor potential vanilloid 1 (TRPV1) activation in peripheral sensory
      nerve is known to be associated with various pain-related diseases, thus TRPV1
      has been the focus as a target for drug discovery. In this study, we
      characterized the pharmacological profiles of (3S)-3-(hydroxymethyl)-4-(5
      methylpyridin-2-yl)-N-[6-(2,2,2-trifluoroethoxy)pyridin-3-yl]-3,4-dihydro-2H
      benzo[b][1,4]oxazine-8-carboxamide (JTS-653), a novel TRPV1 antagonist. JTS-653
      displaced [(3)H]resiniferatoxin binding to human and rat TRPV1. JTS-653
      competitively antagonized the capsaicin-induced activation of human TRPV1 with
      pA(2) values of 10.1. JTS-653 also inhibited proton-induced activation of human
      and rat TRPV1 with IC(50) values of 0.320 and 0.347 nM, respectively.
      Electrophysiological studies indicated that JTS-653 blocked heat-induced inward
      currents in rat TRPV1 with IC(50) values of 1.4 nM. JTS-653 showed weak or no
      inhibitory effects on other TRP channels, receptors, and enzymes. JTS-653
      significantly prevented capsaicin-induced mechanical hyperalgesia at 1 mg/kg p.o.
      and attenuated carrageenan-induced mechanical hyperalgesia at 0.3 mg/kg p.o. JTS
      653 significantly attenuated carrageenan-induced thermal hyperalgesia at 0.1
      mg/kg p.o. and fully reversed at 0.3 mg/kg p.o. without affecting the volume of
      the carrageenan-treated paw. JTS-653 showed a transient increase of body
      temperature at 0.3 mg/kg p.o. These results indicated that JTS-653 is a highly
      potent and selective TRPV1 antagonist in vitro and in vivo and suggested that JTS
      653 is one of the most potent TRPV1 antagonists. The profiles of JTS-653, high
      potency in vivo and transient hyperthermia, seem to be associated with polymodal
      inhibition of TRPV1 activation.

PMID- 22588259
TI  - Pharmacological characterization of abediterol, a novel inhaled beta(2)
      adrenoceptor agonist with long duration of action and a favorable safety profile
      in preclinical models.
AB  - Abediterol is a novel potent, long-acting inhaled beta(2)-adrenoceptor agonist in
      development for the treatment of asthma and chronic obstructive pulmonary
      disease. Abediterol shows subnanomolar affinity for the human beta(2)
      adrenoceptor and a functional selectivity over beta(1)-adrenoceptors higher than
      that of formoterol and indacaterol in both a cellular model with overexpressed
      human receptors and isolated guinea pig tissue. Abediterol is a full agonist at
      the human beta(2)-adrenoceptor (E(max) = 91 +/- 5% of the maximal effect of
      isoprenaline). The potency and onset of action that abediterol shows in isolated
      human bronchi (EC(50) = 1.9 +/- 0.4 nM; t1/2 onset = 7-10 min) is not
      significantly different from that of formoterol, but its duration of action (t1/2
      ~ 690 min) is similar to that of indacaterol. Nebulized abediterol inhibits
      acetylcholine-induced bronchoconstriction in guinea pigs in a concentration
      dependent manner, with higher potency and longer duration of action (t1/2 = 36 h)
      than salmeterol (t1/2 = 6 h) and formoterol (t1/2 = 4 h) and similar duration of
      action to indacaterol up to 48 h. In dogs, the bronchoprotective effect of
      abediterol is more sustained than that of salmeterol and indacaterol at doses
      without effects on heart rate, thus showing a greater safety margin (defined as
      the ratio of dose increasing heart rate by 5% and dose inhibiting bronchospasm by
      50%) than salmeterol, formoterol, and indacaterol (5.6 versus 3.3, 2.2, and 0.3,
      respectively). In conclusion, our results suggest that abediterol has a
      preclinical profile for once-daily dosing in humans together with a fast onset of
      action and a favorable cardiovascular safety profile.

PMID- 22588260
TI  - Differential role of organic anion-transporting polypeptides in estrone-3
      sulphate uptake by breast epithelial cells and breast cancer cells.
AB  - The purpose of this study was to investigate the differential expression and
      function of organic anion-transporting polypeptides (OATPs) in breast epithelial
      and breast cancer cells. Estrone-3-sulfate (E3S), a substrate for 7 of 11 OATPs,
      is a predominant source of tumor estrogen in postmenopausal, hormone-dependent
      patients with breast cancer. Overexpression of certain OATPs (e.g., OATP1A2)
      reported in breast tumor tissues compared with surrounding normal tissues could
      contribute toward two to three times higher tumoral E3S concentration. Little is
      known about expression and function of other OATP family members among breast
      epithelial and breast cancer cells. We therefore compared gene and protein
      expression of seven OATPs (OATP1A2, OATP1B1, OATP1B3, OATP1C1, OATP2B1, OATP3A1,
      and OATP4A1) in immortalized breast epithelial cells (MCF10A), hormone-dependent
      breast cancer cells (MCF7), and hormone-independent breast cancer cells (MDA/LCC6
      435, MDA-MB-231, and MDA-MB-468) by quantitative polymerase chain reaction and
      immunoblotting, respectively. Expression of solute carrier superfamily encoding
      for OATPs (SLCO) 1A2, 1B1, 1B3, 2B1, and 3A1 is exclusive, similar, or
      significantly higher in cancer cells compared with MCF10A cells. Protein
      expression of OATPs is found to be either exclusive or higher in cancer cells
      compared with MCF10A cells. Specificity of OATP-mediated E3S uptake is observed
      only in cancer cells, with the highest total uptake in MCF7 cells. Transport
      kinetics of E3S uptake demonstrates transport efficiency that is 10 times greater
      in the MCF7 cells than in the hormone-independent cells. These data suggest that
      OATPs could be a novel therapeutic target for hormone-dependent breast cancers,
      particularly in postmenopausal patients, where the major source of tumor estrogen
      is E3S.

PMID- 22588261
TI  - Ring substituents on substituted benzamide ligands indirectly mediate
      interactions with position 7.39 of transmembrane helix 7 of the D4 dopamine
      receptor.
AB  - In an effort to delineate how specific molecular interactions of dopamine
      receptor ligand classes vary between D2-like dopamine receptor subtypes, a
      conserved threonine in transmembrane (TM) helix 7 (Thr7.39), implicated as a key
      ligand interaction site with biogenic amine G protein-coupled receptors, was
      substituted with alanine in D2 and D4 receptors. Interrogation of different
      ligand chemotypes for sensitivity to this substitution revealed enhanced affinity
      in the D4, but not the D2 receptor, specifically for substituted benzamides
      (SBAs) having polar 4- (para) and/or 5- (meta) benzamide ring substituents. D4
      T7.39A was fully functional, and the mutation did not alter the sodium-mediated
      positive and negative allostery observed with SBAs and agonists, respectively.
      With the exception of the non-SBA ligand (+)-butaclamol, which, in contrast to
      certain SBAs, had decreased affinity for the D4-T7.39A mutant, the interactions
      of numerous other ligands were unaffected by this mutation. SBAs were docked into
      D4 models in the same mode as observed for eticlopride in the D3 crystal
      structure. In this mode, interactions with TM5 and TM6 residues constrain the SBA
      ring position that produces distal steric crowding between
      pyrrolidinyl/diethylamine moieties and D4-Thr7.39. Ligand-residue interaction
      energy profiles suggest this crowding is mitigated by substitution with a smaller
      alanine. The profiles indicate sites that contribute to the SBA binding
      interaction and site-specific energy changes imparted by the D4-T7.39A mutation.
      Substantial interaction energy changes are observed at only a few positions, some
      of which are not conserved among the dopamine receptor subtypes and thus seem to
      account for this D4 subtype-specific structure-activity relationship.

PMID- 22588262
TI  - Regional variation in recommended treatments for ischemic stroke and TIA: Get
      with the Guidelines--Stroke 2003-2010.
AB  - BACKGROUND AND PURPOSE: Secondary stroke prevention treatments vary in different
      regions of the US. We determined the degree to which guideline-recommended stroke
      treatments vary by region for patients treated at hospitals participating in a
      voluntary national quality improvement program, Get with ehe Guidelines--Stroke.
      METHODS: Receipt of 8 guideline-recommended treatments (intravenous tissue-type
      plasminogen activator, antihypertensives, antithrombotics, anticoagulants for
      atrial fibrillation, deep vein thrombosis prophylaxis, lipid-lowering medications
      at discharge, smoking cessation counseling, weight loss education) and defect
      free care were compared in 4 US regions among eligible patients with ischemic
      stroke and transient ischemic attack; there was adjustment for patient
      demographics, medical history, and hospital characteristics. RESULTS: Among 991
      995 admissions (South, 37%; Northeast, 27.6%; Midwest, 19.3%; West, 15.9%).
      Receipt varied regionally for tissue-type plasminogen activator (58.2%-67.8%),
      lipid-lowering medications (72.5%-75.7%), antihypertensives (80.1%-83.6%),
      antithrombotics (95.6%-96.8%), deep vein thrombosis prophylaxis (88.0%-91.4%),
      weight loss education (49.3%-54.7%), and defect-free care (72.1%-76.5%). In
      adjusted analyses, patients in the South had lower odds of use of intravenous
      tissue-type plasminogen activator (OR [95% CI]; 0.82 [0.69-0.97]),
      antihypertensives (0.82 [0.67-0.99]), and defect-free care (0.83 [0.75-0.92]);
      but, they were more likely to receive lipid-lowering medications (1.28 [1.05
      1.54]) compared with those in the Northeast. Patients in the Midwest had lower
      odds of intravenous tissue-type plasminogen activator administration (0.82 [0.68
      0.99]) and defect-free care (0.81 [0.72-0.92]). Those in the West had lower odds
      of antihypertensives (0.81 [0.67-0.99]), but had greater odds of receiving lipid
      lowering medications (1.26 [1.03-1.53]). CONCLUSIONS: Despite relatively high
      rates of adherence to stroke-related therapies in Get With The Guidelines-Stroke
      hospitals, regional variations exist, with over one quarter of patients receiving
      suboptimal care. Systematic improvements may lead to better patient outcomes.

PMID- 22588263
TI  - Oxygen imaging by MRI: can blood oxygen level-dependent imaging depict the
      ischemic penumbra?

PMID- 22588264
TI  - Upregulation of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E2 synthase
      1 (mPGES-1) in wall of ruptured human cerebral aneurysms: preliminary results.
AB  - BACKGROUND AND PURPOSE: Cyclooxygenase-2 (COX-2) and Microsomal Prostaglandin E2
      Synthase-1 (mPGES-1) catalyze isomerization of the cyclooxygenase product PGH2
      into PGE2. Deletion of COX-2/mPGES-1 suppresses carotid artery atherogenesis and
      angiotensin II-induced aortic aneurysms formation, and attenuates neointimal
      hyperplasia after vascular injury in mice. The upregulation of COX-2/mPGES-1 in
      the wall of ruptured human cerebral aneurysms is not known. METHODS: Ten patients
      with intracranial aneurysms (5 ruptured and 5 nonruptured) underwent
      microsurgical clipping. During the procedure, a segment of the aneurysm dome was
      resected and immunostained with monoclonal antibodies for COX-1, COX-2, and mPGES
      1. A segment of the superficial temporal artery was also removed and
      immunostained with monoclonal antibodies for COX-1, COX-2, and mPGES-1. RESULTS:
      All 10 aneurysm tissues stained positive for mPGES-1 monoclonal antibody.
      Expression of mPGES-1 was more abundant in ruptured aneurysm tissue than in
      nonruptured aneurysms, based on a semiquantitative grading. None of the
      superficial temporal artery specimens expressed mPGES-1. COX-2 was upregulated in
      the same distribution as was mPGES-1. COX-1 was present constitutively in all
      tissues. CONCLUSIONS: COX-2/mPGES-1 are expressed in the wall of human cerebral
      aneurysms and more abundantly so in ruptured aneurysms than in nonruptured. We
      speculate that the protective effect of aspirin against rupture of cerebral
      aneurysms may be mediated in part by inhibition of COX-2/mPGES-1.

PMID- 22588265
TI  - Differentiation of transverse sinus thrombosis from congenitally atretic cerebral
      transverse sinus with CT.
AB  - BACKGROUND AND PURPOSE: Transverse sinus thrombosis can have nonspecific clinical
      and radiographic signs. We hypothesized that the novel "sigmoid notch sign" (on
      head CT) can help differentiate transverse sinus thrombosis from a congenitally
      atretic sinus among individuals with absent signal in 1 transverse sinus by MR
      venography. METHODS: We retrospectively evaluated 53 subjects with a unilaterally
      absent transverse sinus signal on MR venography. Eleven had true transverse sinus
      thrombosis and 42 had an atretic transverse sinus. Reviewers were trained in the
      sigmoid notch sign: "positive" if 1 of the sigmoid notches was asymmetrically
      smaller than the other, consistent with a congenitally absent transverse sinus on
      that side. This sign was scored on CT scans by 2 blinded reviewers to determine
      if signal dropout was clot or atretic sinus. A consensus rating was reached when
      the reviewers disagreed. Characteristics of the sigmoid notch sign as a
      diagnostic test were compared with a gold standard of full chart review by an
      independent reviewer. RESULTS: Each reviewer had a sensitivity of 91% (detecting
      10 of 11 clots based on a negative sigmoid notch sign) and specificity of 71% to
      81%; consensus specificity increased to 86% (36 of 42 individuals with an atretic
      sinus had a positive notch sign, detecting atretic sinuses based on presence of
      the sign). CONCLUSIONS: Asymmetries of the sigmoid notches on noncontrast brain
      CT is a very sensitive and specific measure of differentiating transverse sinus
      thrombosis from an atretic transverse sinus when absence of transverse sinus flow
      is visualized on MR venography.

PMID- 22588266
TI  - Statin therapy and the risk of intracerebral hemorrhage: a meta-analysis of 31
      randomized controlled trials.
AB  - BACKGROUND AND PURPOSE: Statin therapy decreases the risk of ischemic stroke. An
      increased risk of intracerebral hemorrhage (ICH) has been observed in some
      studies. To investigate this issue, we performed a meta-analysis of randomized
      controlled trials using statins that reported ICH. METHODS: We performed a
      literature search of Medline, Web of Science, and The Cochrane Library through
      January 25, 2012, and identified additional randomized controlled trials by
      reviewing reference lists of retrieved studies and prior meta-analyses. All
      randomized controlled trials of statin therapy that reported ICH or hemorrhagic
      stroke were included. The primary outcome variable was ICH. Thirty-one randomized
      controlled trials were included. All analyses used random effects models and
      heterogeneity was not observed in any of the analyses. RESULTS: A total of 91,588
      subjects were included in the active group and 91,215 in the control group. There
      was no significant difference in incidence of ICH observed in the active
      treatment group versus control (OR, 1.08; 95% CI, 0.88-1.32; P=0.47). ICH risk
      was not related to the degree of low-density lipoprotein reduction or achieved
      low-density lipoprotein cholesterol. Total stroke (OR, 0.84; 95% CI, 0.78-0.91;
      P<0.0001) and all-cause mortality (OR, 0.92; CI, 0.87-0.96; P=0.0007) were
      significantly reduced in the active therapy group. There was no evidence of
      publication bias. CONCLUSIONS: Active statin therapy was not associated with
      significant increase in ICH in this meta-analysis of 31 randomized controlled
      trials of statin therapy. A significant reduction in all stroke and all-cause
      mortality was observed with statin therapy.

PMID- 22588267
TI  - Planimetric hematoma measurement in patients with intraventricular hemorrhage: is
      total volume a preferred target for reliable analysis?
AB  - BACKGROUND AND PURPOSE: Reliable quantification of both intracerebral hemorrhage
      and intraventricular hemorrhage (IVH) volume is important for hemostatic trials.
      We evaluated the reliability of computer-assisted planimetric volume measurements
      of IVH. METHODS: Computer-assisted planimetry was used to quantify IVH volume.
      Five raters measured IVH volumes, total (intracerebral hemorrhage+IVH) volumes,
      and Graeb scores from 20 randomly selected computed tomography scans twice.
      Estimates of interrater and intrarater reliability were calculated and expressed
      as an intrarater correlation coefficient and an absolute minimum detectable
      difference. RESULTS: Planimetric IVH volume analysis had excellent intra- and
      interrater agreement (intrarater correlation coefficient, 0.96 and 0.92,
      respectively), which was superior to the Graeb score (intrarater correlation
      coefficient, 0.88 and 0.83). Minimum detectable differences for intra- and
      interrater volumes were 12.1 mL and 17.3 mL, and were dependent on the total size
      of the hematoma; hematomas smaller than the median 43.8 mL had lower minimum
      detectable differences, whereas those larger than the median had higher minimum
      detectable differences. Planimetric total hemorrhage volume analysis had the best
      intra- and interrater agreement (intrarater correlation coefficient, 0.99 and
      0.97, respectively). CONCLUSIONS: Computer-assisted planimetric techniques
      provide a reliable measurement of ventricular hematoma volume, but are
      susceptible to higher absolute error when assessing larger hematomas.

PMID- 22588268
TI  - Horizontal plane localization in single-sided deaf adults fitted with a bone
      anchored hearing aid (Baha).
AB  - OBJECTIVES: : One purpose of this investigation was to evaluate the effect of a
      unilateral bone-anchored hearing aid (Baha) on horizontal plane localization
      performance in single-sided deaf adults who had either a conductive or
      sensorineural hearing loss in their impaired ear. The use of a 33-loudspeaker
      array allowed for a finer response measure than has previously been used to
      investigate localization in this population. In addition, a detailed analysis of
      error patterns allowed an evaluation of the contribution of random error and bias
      error to the total rms error computed in the various conditions studied. A second
      purpose was to investigate the effect of stimulus duration and head-turning on
      localization performance. DESIGN: : Two groups of single-sided deaf adults were
      tested in a localization task in which they had to identify the direction of a
      spoken phrase on each trial. One group had a sensorineural hearing loss (SNHL
      group; N = 7), and the other group had a conductive hearing loss (CHL group; N =
      5). In addition, a control group of four normal-hearing adults was tested. The
      spoken phrase was either 1250 msec in duration (a male saying "Where am I coming
      from now?") or 341 msec in duration (the same male saying "Where?"). For the
      longer-duration phrase, subjects were tested in conditions in which they either
      were or were not allowed to move their heads before the termination of the
      phrase. The source came from one of nine positions in the front horizontal plane
      (from -79 degrees  to +79 degrees ). The response range included 33 choices (from
      -90 degrees  to +90 degrees , separated by 5.6 degrees ). Subjects were tested in
      all stimulus conditions, both with and without the Baha device. Overall rms error
      was computed for each condition. Contributions of random error and bias error to
      the overall error were also computed. RESULTS: : There was considerable
      intersubject variability in all conditions. However, for the CHL group, the
      average overall error was significantly smaller when the Baha was on than when it
      was off. Further analysis of error patterns indicated that this improvement was
      primarily based on reduced response bias when the device was on; that is, the
      average response azimuth was nearer to the source azimuth when the device was on
      than when it was off. The SNHL group, on the other hand, had significantly
      greater overall error when the Baha was on than when it was off. Collapsed across
      listening conditions and groups, localization performance was significantly
      better with the 1250 msec stimulus than with the 341 msec stimulus. However, for
      the longer-duration stimulus, there was no significant beneficial effect of head
      turning. Error scores in all conditions for both groups were considerably larger
      than those in the normal-hearing control group. CONCLUSIONS: : On average, single
      sided deaf adults with CHL showed improved localization ability when using the
      Baha, whereas single-sided deaf adults with SNHL showed a decrement in
      performance when using the device. These results may have implications for
      clinical counseling for patients with unilateral hearing impairment.

PMID- 22588269
TI  - Generational differences in the reporting of tinnitus.
AB  - OBJECTIVES: Recent research suggests that hearing impairment is declining among
      older adults compared with earlier generations of the same age. Tinnitus is often
      associated with hearing impairment, so one might hypothesize that the prevalence
      of tinnitus is declining in a similar manner. The purpose of this study was to
      use multigenerational data with repeated measures to determine whether the
      prevalence of tinnitus is declining among more recent generations. DESIGN: Using
      data from the Epidemiology of Hearing Loss Study (1993-1995, 1998-2000, 2003
      2005, and 2009-2010) and the Beaver Dam Offspring Study (2005-2008), the authors
      examined birth cohort patterns in the report of tinnitus for adults aged 45 years
      and older (n =12,689 observations from 5764 participants). Participants were
      classified as having tinnitus if they reported tinnitus in the past year of at
      least moderate severity or that caused difficulty falling asleep. A low-frequency
      (500, 1000, and 2000 Hz) and high-frequency (3000, 4000, 6000, and 8000 Hz) pure
      tone average from the worse ear was used to summarize hearing status. Other
      potential risk factors for tinnitus were also explored to determine if changes in
      the prevalence of these factors over time could explain any observed birth cohort
      differences in the prevalence of tinnitus. These included the following:
      education, history of head injury, history of doctor-diagnosed ear infections,
      history of cardiovascular disease (myocardial infarction, stroke, or angina),
      current noisy job, longest-held job, target shooting in the past year, number of
      concerts ever attended, alcohol use in the past year, doctor diagnosis of
      arthritis, current aspirin use, regular exercise, and consulting with a physician
      in the past year about any hearing/ear problem. Birth cohort effects were modeled
      with alternating logistic regression models which use generalized estimating
      equations to adjust for correlation among repeated measurements over time that
      are nested within families. RESULTS: The report of tinnitus tended to increase
      with more recent birth cohorts compared with earlier birth cohorts. For example,
      at ages 55 to 59 years, 7.6% of participants born between 1935 and 1939 reported
      tinnitus, compared with 11.0% of those born in 1940 to 1944, 13.6% of those born
      between 1945 and 1949, and 17.5% of those born between 1950 and 1954. Similarly,
      at ages 65 to 69 years, 7.9% of participants born between 1925 and 1929 reported
      tinnitus, compared with 10.0% of those born between 1930 and 1934, 11.9% of those
      born between 1935 and 1939, and 13.7% of those born between 1940 and 1944. Final
      alternating logistic regression model results indicated that, on average, after
      adjusting for age and other factors, participants in a given generation were
      significantly more likely to report tinnitus than participants from a generation
      20 years earlier (odds ratio = 1.78, 95% confidence interval = 1.44, 2.21).
      CONCLUSIONS: Increased reports of tinnitus may reflect increased prevalence of
      symptoms, increased awareness of symptoms, or higher health expectations among
      more recent generations of adults. Regardless of the reasons, the increasing
      prevalence of tinnitus suggests that health care providers may see an increased
      number of patients bothered by this common but little understood symptom.

PMID- 22588270
TI  - Sound localization in noise by normal-hearing listeners and cochlear implant
      users.
AB  - OBJECTIVES: This study aimed to characterize horizontal plane sound localization
      in interfering noise at different signal-to-noise ratios (SNRs) and to compare
      performance across normal-hearing listeners and users of unilateral and bilateral
      cochlear implants (CIs). CI users report difficulties with listening in noisy
      environments. Although their difficulties with speech understanding have been
      investigated in several studies, the ability to localize sounds in background
      noise has not extensively been examined, despite the benefits of binaural hearing
      being greatest in noisy situations. Sound localization is a measure of binaural
      processing and is thus well suited to assessing the benefit of bilateral
      implantation. The results will inform clinicians and implant manufacturers how to
      focus their efforts to improve localization with CIs in noisy situations. DESIGN:
      Six normal-hearing listeners, four unilateral, and 10 bilateral CI users
      indicated the perceived location of sound sources using a light pointer method.
      Target sounds were noise pulses played from one of 11 loudspeakers placed between
      -80 and +80 degrees in the frontal horizontal plane in the free field.
      Localization was assessed in quiet and in diffuse background noise at SNRs
      between +10 and -7 dB. Speech reception thresholds were measured and their
      relation to the localization results examined. RESULTS: Localization performance
      declined with decreasing SNR: target sounds were perceived closer to the median
      plane and the standard deviation of responses increased. Localization performance
      across groups was compared using a measure of "Spatial Resolvability" (SR). This
      measure gives the angular separation between two sound sources that would enable
      an ideal observer to correctly distinguish them 69.1% of the time. For all
      participants SR increased with decreasing SNR, that is, at low SNRs the spatial
      separation between sound sources remained distinguishable only when it was
      larger. Normal-hearing participants performed best, with SR between 1.4 and 5.1
      degrees in quiet. Bilateral CI users showed SR between 8.3 and 43.6 degrees in
      quiet, corresponding approximately to the spatial resolution of normal-hearing
      listeners at an SNR of -5 dB. Most bilateral CI users had lost the ability to
      correctly determine which side the sound came from at an SNR of -3 dB. Overall,
      the SNR had to be at least +7 dB to achieve localization performance near to that
      in quiet for all bilateral CI users. No significant correlation was found between
      spatial resolution and speech reception thresholds, but the speech processor
      sensitivity setting did significantly affect performance. Unilateral CI users
      showed the most severe localization problems, with only two of four participants
      being able to correctly determine which side sounds came from in quiet.
      CONCLUSIONS: This study is the first to examine sound localization with CIs at
      various SNRs and to compare it with normal hearing. The results confirm that
      localization with CIs is strongly disrupted in noisy situations. Bilateral CIs
      were shown to be clearly superior over unilateral CIs for localization in quiet
      and in noisy situations. With bilateral CIs, localization declined at moderately
      high absolute noise levels (>63 dB SPL), suggesting that an extension of the
      acoustic-dynamic range to higher levels would be beneficial. The absence of a
      relation between speech reception thresholds and spatial resolution highlights
      the need for additional clinical tests to assess the binaural benefit of a second
      implant.

PMID- 22588271
TI  - PD-1/PD-L1 blockade can enhance HIV-1 Gag-specific T cell immunity elicited by
      dendritic cell-directed lentiviral vaccines.
AB  - Exhaustion of CD8(+) T cells and upregulation of programmed death 1 (PD-1), a
      negative regulator of T cell activation, are characteristic features of
      individuals chronically infected with human immunodeficiency virus type 1. In a
      previous study, we showed in mice that a dendritic cell-directed lentiviral
      vector (DCLV) system encoding the human immunodeficiency virus (HIV)-1 Gag
      protein was an efficient vaccine modality to induce a durable Gag-specific T cell
      immune response. In this study, we demonstrate that blocking of the PD-1/PD-1
      ligand (PD-L) inhibitory signal via an anti-PD-L1 antibody generated an enhanced
      HIV-1 Gag-specific CD8(+) immune response following both a single round of DCLV
      immunization and a homologous prime/boost regimen. The prime/boost regimen
      combined with PD-L1 blockade generated very high levels of Gag-specific CD8(+) T
      cells comprising several valuable features: improved ability to produce multiple
      cytokines, responding to a broader range of Gag-derived epitopes, and long
      lasting memory. This enhanced cellular immune response generated by DCLV
      immunization combined with anti-PD-L1 blockade correlated with improved viral
      control following challenge with Gag-expressing vaccinia virus. Taken together,
      our studies offer evidence to support the use of PD-1/PD-L1 blockade as an
      adjuvant modality to enhance antigen-specific immune responses elicited by T cell
      based immunizations such as DCLV.

PMID- 22588272
TI  - Modulation of eIF5A expression using SNS01 nanoparticles inhibits NF-kappaB
      activity and tumor growth in murine models of multiple myeloma.
AB  - Despite recent advances in the first-line treatment of multiple myeloma, almost
      all patients eventually experience relapse with drug-resistant disease. New
      therapeutic modalities are needed, and to this end, SNS01, a therapeutic
      nanoparticle, is being investigated for treatment of multiple myeloma. The
      antitumoral activity of SNS01 is based upon modulation of eukaryotic translation
      initiation factor 5A (eIF5A), a highly conserved protein that is involved in many
      cellular processes including proliferation, apoptosis, differentiation and
      inflammation. eIF5A is regulated by post-translational hypusine modification, and
      overexpression of hypusination-resistant mutants of eIF5A induces apoptosis in
      many types of cancer cells. SNS01 is a polyethylenimine (PEI)-based nanoparticle
      that contains both a B-cell-specific expression plasmid expressing a non
      hypusinable mutant of eIF5A and a small interfering RNA (siRNA) which depletes
      endogenous hypusinated eIF5A. Reducing hypusine-modified eIF5A levels was found
      to inhibit phosphorylation and activity of ERK MAPK and nuclear factor-kappaB (NF
      kappaB), and thus sensitize myeloma cells to apoptosis resulting from
      transfection of a plasmid expressing eIF5A(K50R). SNS01 exhibited significant
      antitumoral activity in both KAS-6/1 (95% inhibition; P < 0.05) and RPMI 8226
      (59% inhibition; P < 0.05) multiple myeloma xenograft models following systemic
      administration. These results highlight the potential of using this approach as a
      new therapeutic strategy for multiple myeloma.

PMID- 22588274
TI  - New treatments for infrapopliteal disease: devices, techniques, and outcomes so
      far.
AB  - The use of endovascular treatment of infrapopliteal disease has increased in
      popularity in recent years. An improvement in technical success rates due to the
      availability of newer devices has fuelled an increased interest in the subject.
      The pathogenesis, indications for treatment, and outcome measures of
      infrapopliteal disease differ from larger vessel intervention. Diabetes and renal
      failure are prevalent. Neuropathy and venous disease contribute to the etiology
      of ulceration. Most interventions are undertaken for critical limb ischemia
      rather than claudication. Therefore, a range of conservative, pharmacological,
      and invasive therapies are provided. Conventional percutaneous transluminal
      angioplasty (PTA) using modern low-profile systems is associated with high
      technical success rates. However, initial data from recent randomized, controlled
      trials suggest that drug-eluting stents are consistently achieving improved
      patency over PTA alone or over bare metal stents. This review summarizes recent
      advances in the treatment of infrapopliteal disease.

PMID- 22588273
TI  - Sialic acid deposition impairs the utility of AAV9, but not peptide-modified AAVs
      for brain gene therapy in a mouse model of lysosomal storage disease.
AB  - Recombinant vector systems have been recently identified that when delivered
      systemically can transduce neurons, glia, and endothelia in the central nervous
      system (CNS), providing an opportunity to develop therapies for diseases
      affecting the brain without performing direct intracranial injections. Vector
      systems based on adeno-associated virus (AAV) include AAV serotype 9 (AAV9) and
      AAVs that have been re-engineered at the capsid level for CNS tropism. Here, we
      performed a head-to-head comparison of AAV9 and a capsid modified AAV for their
      abilities to rescue CNS and peripheral disease in an animal model of lysosomal
      storage disease (LSD), the mucopolysacharidoses (MPS) VII mouse. While the
      peptide-modified AAV reversed cognitive deficits, improved storage burden in the
      brain, and substantially prolonged survival, we were surprised to find that AAV9
      provided no CNS benefit. Additional experiments demonstrated that sialic acid, a
      known inhibitor of AAV9, is elevated in the CNS of MPS VII mice. These studies
      highlight how disease manifestations can dramatically impact the known tropism of
      recombinant vectors, and raise awareness to assuming similar transduction
      profiles between normal and disease models.

PMID- 22588275
TI  - MR-guided neurolytic celiac plexus ablation: an evaluation of effect and
      injection spread pattern in cancer patients with celiac tumor infiltration.
AB  - OBJECTIVE: The purpose of this study was to evaluate the feasibility, the initial
      accuracy, and the effects of the MR-guided neurolytic celiac plexus ablation as a
      method to treat cancer-induced chronic abdominal pain. METHODS: Thirteen celiac
      plexus ablations were performed for 12 patients. A 0.23-T open MRI scanner with
      optical navigation was used for procedural guidance. As an adjunct to the MR
      guided needle positioning, the needle location was confirmed with saline
      injection and consequent MR imaging (STIR sequence). The spread of the ablative
      injection material (alcohol-lidocaine mix) was observed by repeating this
      sequence after the therapeutic injection. Pain scores from seven patients (eight
      ablations) were used to assess the therapy effect. RESULTS: MR guidance allowed
      adequate needle positioning and visualization of injection material in all cases.
      The rest pain scores significantly decreased from 4 (median) at baseline to 1
      (median) at 2 weeks (p < 0.05). Average and worst pain experienced during the
      past week were significantly lower at the 2-week time point compared with the
      baseline (p < 0.05). However, the intervention did not result in reduction of
      opioid use at 2 weeks. CONCLUSIONS: MR guidance is an accurate and safe method
      for celiac plexus ablation with positive therapeutic effect.

PMID- 22588276
TI  - Life-threatening cerebral edema caused by acute occlusion of a superior vena cava
      stent.
AB  - A71-year-old man with advanced lung cancer developed a life-threatening cerebral
      edema caused by the acute occlusion of a superior vena cava (SVC) stent and was
      successfully treated by an additional stent placement. Although stent occlusion
      is a common early complication, no life-threatening situations have been reported
      until now. Our experience highlights the fact that acute stent occlusion can
      potentially lead to the complete venous shutdown of the SVC, resulting in life
      threatening cerebral edema, after SVC stent placement. Immediate diagnosis and
      countermeasures are required.

PMID- 22588277
TI  - Elevated resting heart rate is an independent predictor of all-cause death and
      cardiovascular events in Japanese ambulatory hemodialysis patients.
AB  - BACKGROUND: Elevated heart rate (HR) is an independent risk factor for all-cause
      death or cardiovascular events in non-hemodialysis subjects; however, the
      clinical significance of elevated HR in hemodialysis patients is not well
      studied. METHODS: We prospectively evaluated the relationship between HR and
      adverse outcome in a total of 229 ambulatory hemodialysis patients (57 % men;
      mean age 62.2 years) recruited from two dialysis clinics in 2009. Mean (SD) HR of
      this cohort was 74.1 (11.0) beats per minute (bpm). RESULTS: Receiver operating
      characteristic curves identified an HR cut-off level of >=80 bpm for increased
      adverse outcome. After a mean follow-up of 525 days (range 7-760 days) a total of
      30 primary endpoints (21 all-cause deaths, 4 acute coronary syndromes and 8
      strokes) and 38 secondary endpoints (30 primary endpoints, 8 congestive heart
      failures, and 5 other cardiovascular events) were detected. Cox regression
      analysis revealed that HR >80 bpm was not an independent predictor of primary
      endpoints [hazard ratio 1.81, 95 % confidence interval (CI) 0.79-4.11, p = NS],
      but of secondary endpoints (hazard ratio 2.01, 95 % CI 1.01-4.22, p < 0.05) after
      adjusting for age, sex, hemodialysis duration, and cardiovascular risks.
      CONCLUSIONS: Elevated HR is an independent predictor of all-cause death and
      cardiovascular events in Japanese ambulatory hemodialysis patients.

PMID- 22588280
TI  - Barbara Hepworth and the tonsillectomy.
AB  - The Garnett Passe and Rodney Williams Foundation, a major medical research
      foundation in Melbourne, has recently acquired a hitherto unknown and
      uncatalogued painting by Dame Barbara Hepworth, the celebrated British sculptor
      and artist. It is of the Foundation's nominal patron Garnett Passe performing a
      tonsillectomy, probably at the London Clinic, in 1948. This article gives an
      account of Barbara Hepworth and her relationships with Garnett Passe and Norman
      Capener, the two surgeons who introduced her to this subject and who led to the
      creation of this unique work of art.

PMID- 22588279
TI  - AKT-mediated regulation of polarization in differentiated human neutrophil-like
      HL-60 cells.
AB  - OBJECTIVES: Neutrophil polarization is critical for the inflammatory response.
      AKT is a serine/threonine protein kinase and has been implicated in cell
      migration. However, it is not completely clear whether AKT affects neutrophil
      polarization. In this study, we tested the hypothesis that AKT regulates the
      polarization of neutrophil-like differentiated HL-60 cells (dHL-60) in response
      to fMLP. METHODS: HL-60 cells were differentiated into dHL-60 by incubation in
      medium containing 1.3 % DMSO for up to 6 days. Polarization of dHL-60 cells and
      primary human neutrophils were measured by Zigmond chamber. Phospho-Akt was
      analyzed by immunofluorescence and Western blot analysis. F-actin polymerization
      was detected by Rhodamine-Phalloidine staining. Rac2 activation was evaluated
      using GST Pull-down assay. RESULTS: We found that changes in the rate of cell
      polarization were consistent with the changes in AKT phosphorylation levels
      during HL-60 cell differentiation in response to fMLP. Moreover, cell
      polarization and AKT phosphorylation were reduced in fMLP-stimulated dHL-60 cells
      pretreated with the PI3 kinase inhibitors or the AKT inhibitors, which was
      confirmed in the primary human neutrophils. The AKT inhibitors altered fMLP
      induced F-actin polymerization. Rac2 GTPases was also decreased by the AKT
      inhibitors in fMLP-stimulated dHL-60 cells. CONCLUSION: This study demonstrates
      that AKT activation plays a crucial role in dHL-60 cell polarization.

PMID- 22588278
TI  - Inflammatory markers and bariatric surgery: a meta-analysis.
AB  - OBJECTIVE: Obesity is a state of chronic low grade inflammation with increased
      levels of inflammatory markers such as C-reactive protein (CRP), interleukin (IL)
      6 and tumor necrosis factor (TNF) alpha. The changes of some of the above markers
      after bariatric surgery are not consistent across studies. The objective of this
      study is to confirm the changes in blood levels of CRP, IL-6 and TNFalpha after
      bariatric surgery. METHODS: A Pubmed and EMBASE search was performed for studies
      measuring the above cytokines in blood before and after bariatric surgery. A meta
      analysis was performed for the changes in CRP, TNFalpha and IL-6 for the maximum
      follow-up time in each study as well as for discrete follow-up times. RESULTS:
      Only observational studies could be retrieved. Bariatric surgery produces about
      66 and 27 % reduction in CRP and IL-6 levels, respectively. The change in
      TNFalpha after bariatric surgery did not approach statistical significance.
      CONCLUSION: Bariatric surgery decreases the low grade inflammation associated
      with obesity as measured by CRP and IL-6 levels. The change of TNFalpha after
      bariatric surgery should be further investigated with randomized trials.

PMID- 22588281
TI  - A microfluidic device for whole-animal drug screening using electrophysiological
      measures in the nematode C. elegans.
AB  - This paper describes the fabrication and use of a microfluidic device for
      performing whole-animal chemical screens using non-invasive electrophysiological
      readouts of neuromuscular function in the nematode worm, C. elegans. The device
      consists of an array of microchannels to which electrodes are attached to form
      recording modules capable of detecting the electrical activity of the pharynx, a
      heart-like neuromuscular organ involved in feeding. The array is coupled to a
      tree-like arrangement of distribution channels that automatically delivers one
      nematode to each recording module. The same channels are then used to perfuse the
      recording modules with test solutions while recording the electropharyngeogram
      (EPG) from each worm with sufficient sensitivity to detect each pharyngeal
      contraction. The device accurately reported the acute effects of known
      anthelmintics (anti-nematode drugs) and also correctly distinguished a specific
      drug-resistant mutant strain of C. elegans from wild type. The approach described
      here is readily adaptable to parasitic species for the identification of novel
      anthelmintics. It is also applicable in toxicology and drug discovery programs
      for human metabolic and degenerative diseases for which C. elegans is used as a
      model.

PMID- 22588283
TI  - Carbon self-doping induced high electronic conductivity and photoreactivity of g
      C3N4.
AB  - We theoretically and experimentally demonstrate that carbon self-doping could
      induce intrinsic electronic and band structure change of g-C(3)N(4)via the
      formation of delocalized big pi bonds to increase visible light absorption and
      electrical conductivity as well as surface area and thus enhance both
      photooxidation and photoreduction activities.

PMID- 22588282
TI  - Electroantennographic bioassay as a screening tool for host plant volatiles.
AB  - Plant volatiles play an important role in plant-insect interactions. Herbivorous
      insects use plant volatiles, known as kairomones, to locate their host plant.
      When a host plant is an important agronomic commodity feeding damage by insect
      pests can inflict serious economic losses to growers. Accordingly, kairomones can
      be used as attractants to lure or confuse these insects and, thus, offer an
      environmentally friendly alternative to pesticides for insect control.
      Unfortunately, plants can emit a vast number volatiles with varying compositions
      and ratios of emissions dependent upon the phenology of the commodity or the time
      of day. This makes identification of biologically active components or blends of
      volatile components an arduous process. To help identify the bioactive components
      of host plant volatile emissions we employ the laboratory-based screening
      bioassay electroantennography (EAG). EAG is an effective tool to evaluate and
      record electrophysiologically the olfactory responses of an insect via their
      antennal receptors. The EAG screening process can help reduce the number of
      volatiles tested to identify promising bioactive components. However, EAG
      bioassays only provide information about activation of receptors. It does not
      provide information about the type of insect behavior the compound elicits; which
      could be as an attractant, repellent or other type of behavioral response.
      Volatiles eliciting a significant response by EAG, relative to an appropriate
      positive control, are typically taken on to further testing of behavioral
      responses of the insect pest. The experimental design presented will detail the
      methodology employed to screen almond-based host plant volatiles by measurement
      of the electrophysiological antennal responses of an adult insect pest navel
      orangeworm (Amyelois transitella) to single components and simple blends of
      components via EAG bioassay. The method utilizes two excised antennae placed
      across a "fork" electrode holder. The protocol demonstrated here presents a
      rapid, high-throughput standardized method for screening volatiles. Each volatile
      is at a set, constant amount as to standardize the stimulus level and thus allow
      antennal responses to be indicative of the relative chemoreceptivity. The
      negative control helps eliminate the electrophysiological response to both
      residual solvent and mechanical force of the puff. The positive control (in this
      instance acetophenone) is a single compound that has elicited a consistent
      response from male and female navel orangeworm (NOW) moth. An additional
      semiochemical standard that provides consistent response and is used for bioassay
      studies with the male NOW moth is (Z,Z)-11,13-hexdecadienal, an aldehyde
      component from the female-produced sex pheromone.

PMID- 22588284
TI  - Vertical phase separation of conjugated polymer and fullerene bulk heterojunction
      films induced by high pressure carbon dioxide treatment at ambient temperature.
AB  - The morphology of bulk-heterojunctions (BHJ) is critically important for
      conjugated polymer and fullerene blend solar cells. To alter the morphology, high
      pressure (gas phase) carbon dioxide (CO(2)) treatment is applied to poly(3-hexyl
      thiophene) (P3HT) and [6,6]-phenyl-C61 butyric acid methyl ester (PCBM) blend
      films under ambient temperature. This process can achieve vertically phase
      separated morphology such that PCBM distributes toward the film surface, which is
      suggested by secondary ion mass spectroscopy (SIMS), contact angle, X-ray
      photoelectron spectroscopy (XPS) and cross-sectional scanning electron microscope
      (SEM) studies. While pristine P3HT films do not show a significant change upon
      CO(2) treatment, pristine PCBM films are plasticized in high pressure CO(2).
      Thus, PCBM is selectively plasticized by CO(2) in the blend film and is drawn
      towards the surface due to depressed surface energy, although P3HT tends to
      distribute around the surface without CO(2). This stratification process can
      enhance solar cell performance. 55% improvement is achieved in the power
      conversion efficiency of the CO(2) treated device compared to the untreated one,
      indicating that CO(2) treatment can be a good candidate for optimizing the
      morphology and enhancing the performance of BHJ polymer solar cells.

PMID- 22588285
TI  - Foreword. Reproductive physiology of fish.

PMID- 22588286
TI  - Epidural catheter insertion during general anesthesia.

PMID- 22588287
TI  - Prediction of volume responsiveness using pleth variability index in patients
      undergoing cardiac surgery after cardiopulmonary bypass.
AB  - BACKGROUND: The pleth variability index (PVI) is derived from analysis of the
      plethysmographic curve and is considered to be a noninvasive parameter for
      prediction of volume responsiveness. The aim of our prospective clinical study
      was to evaluate if volume responsiveness can be predicted by PVI in patients
      undergoing cardiac surgery after cardiopulmonary bypass. METHODS: Eighteen
      patients were prospectively studied. Directly after cardiac surgery, PVI, stroke
      volume variation (SVV), and cardiac index (CI) were recorded. Colloid infusion (4
      ml/kg body weight) was used for volume loading, and volume responsiveness was
      defined as increase of CI more than 10 %. RESULTS: SVV and PVI measures were
      found to be highly correlated at r = 0.80 (p < 0.001). Receiver operating
      characteristics curve (ROC) analysis resulted in an area under the curve of 0.87
      for SVV and 0.95 for PVI, which values did not differ statistically significant
      from each other (p > 0.05). The optimal threshold value given by ROC analysis was
      >=11 % for SVV with a sensitivity and specificity of 100 % and 72.2 %. For PVI,
      optimal threshold value was >=16 % with a sensitivity and specificity of 100 %
      and 88.9 %. Positive and negative predictive values estimating an increase of CI
      >=10 % for SVV were 44.4 % and 100 % and 66.7 % and 100 % for PVI. CONCLUSIONS:
      For consideration of fluid responsiveness PVI is as accurate as SVV in patients
      after cardiopulmonary bypass. Methodological limitations such as instable cardiac
      rhythm after cardiopulmonary bypass and right- or left ventricular impairment
      seem to be responsible for low specificity and positive predictive values in both
      parameters PVI and SVV.

PMID- 22588288
TI  - Management of strabismus with hemianopic visual field defects.
AB  - BACKGROUND: Hemianopia and strabismus leads to severe disturbance of visual
      orientation and diplopia under binocular conditions if the deviated eye has a
      normal retinal localization. SUBJECTS AND METHODS: Four cases with homonymous
      (two) and bitemporal (two) hemianopia and strabismus will be described with
      respect to binocular visual field and diplopia/confusion. All of them were
      recommended for strabismus surgery. Preoperatively, prism adaptation test was
      carried out to analyze functional results and fusional competence. In three of
      the four cases, strabismus surgery was successfully performed to avoid
      diplopia/confusion. All three patients revealed normal retinal correspondence.
      Furthermore, in two cases surgery led to an extension of binocular visual field;
      in one case with a bitemporal hemianopia and hemifield-slide phenomenon, blurred
      central vision and reading problems reduced significantly postoperatively. In one
      patient with anomalous retinal correspondence due to early childhood trauma
      exotropia led to an extension of the binocular visual field. In this case,
      strabismus surgery would have been unfavourable. RESULTS: Case 1 showed a
      homonymous hemianopia to the left and acquired exotropia of the right eye,
      leading to binocular diplopia. Case 2 with homonymous hemianopia to the right and
      exotropia of right eye revealed anomalous retinal correspondence after history of
      perinatal brain injury, resulting in absence of diplopia and enlargement of
      visual field to the right. Cases 3 and 4 with bitemporal hemianopia suffered from
      sensory disturbances caused by additional acquired strabismus. The exodeviation
      of the right eye in case 3 led to a restriction of binocular visual field with
      overlap of the nasal parts causing diplopia, whereas the esodeviation of case 4
      resulted in a "gap" between the nasal parts (blind area). CONCLUSION: Depending
      on the extent of visual field defects and on retinal correspondence, functional
      consequences for binocular vision and binocular visual field should be considered
      prior to surgery. In normal retinal correspondence, strabismus surgery will be
      indicated in most cases because of diplopia. However, surgery might result in a
      reduction of binocular visual field. Preoperatively, it is important to map
      monocular and binocular visual fields, to examine retinal correspondence, and to
      undertake prism adaptation test to imitate the postoperative functional result
      and risk of double vision.

PMID- 22588289
TI  - Pars plana vitrectomy for the repair of primary, inferior rhegmatogenous retinal
      detachment associated to inferior breaks. A comparison of a 25-gauge versus a 20
      gauge system.
AB  - BACKGROUND: To compare anatomical, functional outcomes and complications of high
      speed 25-gauge (G) pars plana vitrectomy (PPV) versus 20-G PPV for the management
      of primary inferior rhegmatogenous retinal detachment (RRD) associated to
      inferior breaks/holes. METHODS: Eighty-five eyes from 85 patients with a minimum
      follow-up of 3 months were retrospectively evaluated. Forty-one patients
      underwent 25-G and 44 patients underwent 20-G PPV. All patients underwent PPV
      with fluid-air exchange, sulfur hexafluoride (SF6) 20 % gas tamponade and laser
      or cryo retinopexy. RESULTS: The mean follow-up interval was 6.51(+/- 2.32) and
      6.63 (+/- 2.58) months in the 25-G and 20-G groups respectively. Single-operation
      success rate was 92.7 % for the 25-G group and 81.8 % for the 20-G group (P =
      0.24). Post-operative hypotony was observed in no case. Redetachment occurred in
      3 eyes operated on with 25-G and in 8 eyes operated on with 20-G system. All
      retinas were attached at final follow-up. Logarithm of the minimum angle of
      resolution visual acuity significantly improved from 0.69 +/- 0.76 to 0.33 +/-
      0.37 in the 25-G and from 0.47 +/- 0.59 to 0.21 +/- 0.28 in the 20-G group (P =
      0.0007 and P < 0.0001 respectively). CONCLUSIONS: High-speed PPV and SF6 gas
      tamponade using either 25-G or 20-G PPV system, yields similar single operation
      anatomical success rates for the repair of uncomplicated, primary inferior RRDs
      associated to inferior breaks.

PMID- 22588290
TI  - Analysis of internal astigmatism and higher order aberrations in eyes implanted
      with a new diffractive multifocal toric intraocular lens.
AB  - BACKGROUND: To evaluate the intraocular lens (IOL) position by analyzing the
      postoperative axis of internal astigmatism as well as the higher-order aberration
      (HOA) profile after cataract surgery following the implantation of a diffractive
      multifocal toric IOL METHODS: Prospective study including 51 eyes with corneal
      astigmatism of 1.25D or higher of 29 patients with ages ranging between 20 and 61
      years old. All cases underwent uneventful cataract surgery with implantation of
      the AT LISA 909 M toric IOL (Zeiss). Visual, refractive and corneal topograpy
      changes were evaluated during a 12-month follow-up. In addition, the axis of
      internal astigmatism as well as ocular, corneal, and internal HOA (5-mm pupil)
      were evaluated postoperatively by means of an integrated aberrometer (OPD Scan
      II, Nidek). RESULTS: A significant improvement in uncorrected distance and near
      visual acuities (p < 0.01) was found, which was consistent with a significant
      correction of manifest astigmatism (p < 0.01). No significant changes were
      observed in corneal astigmatism (p = 0.32). With regard to IOL alignment, the
      difference between the axes of postoperative internal and preoperative corneal
      astigmatisms was close to perpendicularity (12 months, 87.16 degrees  +/- 7.14),
      without significant changes during the first 6 months (p >= 0.46). Small but
      significant changes were detected afterwards (p = 0.01). Additionally, this
      angular difference correlated with the postoperative magnitude of manifest
      cylinder (r = 0.31, p = 0.03). Minimal contribution of intraocular optics to the
      global magnitude of HOA was observed. CONCLUSIONS: The diffractive multifocal
      toric IOL evaluated is able to provide a predictable astigmatic correction with
      apparent excellent levels of optical quality during the first year after
      implantation.

PMID- 22588291
TI  - Hexahomotrioxacalix[3]arene derivatives as ionophores for molecular recognition
      of dopamine, serotonin and phenylethylamine.
AB  - The lower rim functionalized hexahomotrioxacalix[3]arene derivatives cone-3 and
      cone-5 bearing three benzyl and three N,N-diethyl-2-aminoethoxy groups,
      respectively, were synthesized from triol 1. Their complexation with 2-(3,4
      dihydroxyphenyl)ethylamine (dopamine), 5-hydroxytryptamine (serotonin), and 2
      phenylethylamine (phenethylamine), which have biologically important activities,
      has been studied by (1)H-NMR spectroscopy. The chemical shifts of the aromatic
      protons of the host and guest molecules and the up-field shifts of the ethyl
      protons of the guest molecules strongly suggest the formation of inclusion
      complexes in solution. The formation of the host-guest complexes is assisted by a
      hydrogen bond and/or an electrostatic interaction between the host and ammonium
      ion (RNH(3)(+)) of the guest. The structures of receptors cone-3 and cone-5 have
      been determined by X-ray crystallography.

PMID- 22588292
TI  - Resonant magnetic exciton mode in the heavy-fermion antiferromagnet CeB6.
AB  - Resonant magnetic excitations are recognised as hallmarks of unconventional
      superconductivity in copper oxides, iron pnictides and heavy-fermion compounds.
      Model calculations have related these modes to the microscopic properties of the
      pair wave function, but the mechanisms of their formation are still debated. Here
      we report the discovery of a similar resonant mode in the non-superconducting
      antiferromagnetic heavy-fermion metal CeB(6). Unlike conventional magnons, the
      mode is non-dispersive and is sharply peaked around a wave vector separate from
      those characterising the antiferromagnetic order. It is likely associated with a
      co-existing order parameter of the unusual antiferro-quadrupolar phase of CeB(6),
      which has long remained hidden to neutron-scattering probes. The mode energy
      increases continuously below the onset temperature for antiferromagnetism, in
      parallel to the opening of a nearly isotropic spin gap throughout the Brillouin
      zone. These attributes are similar to those of the resonant modes in
      unconventional superconductors. This unexpected commonality between the two
      disparate ground states indicates the dominance of itinerant spin dynamics in the
      ordered low-temperature phases of CeB(6) and throws new light on the interplay
      between antiferromagnetism, superconductivity and 'hidden' order parameters in
      correlated-electron materials.

PMID- 22588293
TI  - Switching of macroscopic molecular recognition selectivity using a mixed solvent
      system.
AB  - The formation of macroscopic assemblies based on molecular recognition is
      promising in a wide variety of fields of materials science. Switching of the
      selectivity of macroscopic assemblies is of increasing importance to produce
      highly functional materials. Here we show macroscopic assembly based on molecular
      recognition using polyacrylamide gel modified with pyrenyl (Py) moiety (Py-gel)
      and gels possessing CD moieties (alphaCD-gel, betaCD-gel and gammaCD-gel) in a
      mixed solvent of water and dimethyl sulfoxide. Changing the composition of the
      mixed solvent can switch the selectivity of Py-gel, because the fractions of the
      monomer and dimer of the Py moieties on the gel surface depend on the mixed
      solvent composition. The monomer and dimer of the Py moieties prefer betaCD and
      gammaCD moieties, respectively.

PMID- 22588294
TI  - The origin of pelletal lapilli in explosive kimberlite eruptions.
AB  - Kimberlites are volatile-rich magmas from mantle depths of >= 150  km and are the
      primary source of diamonds. Kimberlite volcanism involves the formation of
      diverging pipes or diatremes, which are the locus of high-intensity explosive
      eruptions. A conspicuous and previously enigmatic feature of diatreme fills are
      'pelletal lapilli'--well-rounded clasts consisting of an inner 'seed' particle
      with a complex rim, thought to represent quenched juvenile melt. Here we show
      that these coincide with a transition from magmatic to pyroclastic behaviour,
      thus offering fundamental insights into eruption dynamics and constraints on vent
      conditions. We propose that pelletal lapilli are formed when fluid melts intrude
      into earlier volcaniclastic infill close to the diatreme root zone. Intensive
      degassing produces a gas jet in which locally scavenged particles are
      simultaneously fluidised and coated by a spray of low-viscosity melt. A similar
      origin may apply to pelletal lapilli in other alkaline volcanic rocks, including
      carbonatites, kamafugites and melilitites.

PMID- 22588295
TI  - Giant nonlinear optical activity in a plasmonic metamaterial.
AB  - In 1950, a quarter of a century after his first-ever nonlinear optical experiment
      when intensity-dependent absorption was observed in uranium-doped glass, Sergey
      Vavilov predicted that birefringence, dichroism and polarization rotatory power
      should be dependent on light intensity. It required the invention of the laser to
      observe the barely detectable effect of light intensity on the polarization
      rotatory power of the optically active lithium iodate crystal, the phenomenon now
      known as the nonlinear optical activity, a high-intensity counterpart of the
      fundamental optical effect of polarization rotation in chiral media. Here we
      report that a plasmonic metamaterial exhibits nonlinear optical activity 30
      million times stronger than lithium iodate crystals, thus transforming this
      fundamental phenomenon of polarization nonlinear optics from an esoteric
      phenomenon into a major effect of nonlinear plasmonics with potential for
      practical applications.

PMID- 22588296
TI  - Abyssal undular vortices in the Eastern Mediterranean basin.
AB  - Abyssal temperature and velocity observations performed within the framework of
      the Neutrino Mediterranean Observatory, a project devoted to constructing a km(3)
      scale underwater telescope for the detection of high-energy cosmic neutrinos,
      demonstrate cross-fertilization between subnuclear physics and experimental
      oceanography. Here we use data collected south of Sicily in the Ionian abyssal
      plain of the Eastern Mediterranean (EM) basin to show for the first time that
      abyssal vortices exist in the EM, at depths exceeding 2,500 m. The eddies consist
      of chains of near-inertially pulsating mesoscale cyclones/anticyclones. They are
      embedded in an abyssal current flowing towards North-Northwest. The paucity of
      existing data does not allow for an unambiguous determination of the vortex
      origin. A local generation mechanism seems probable, but a remote genesis cannot
      be excluded a priori. The presence of such eddies adds further complexity to the
      discussion of structure and evolution of water masses in the EM.

PMID- 22588297
TI  - Contrasting arbuscular mycorrhizal responses of vascular and non-vascular plants
      to a simulated Palaeozoic CO2 decline.
AB  - The arbuscular mycorrhizal (AM) fungal symbiosis is widely hypothesized to have
      promoted the evolution of land plants from rootless gametophytes to rooted
      sporophytes during the mid-Palaeozoic (480-360 Myr, ago), at a time coincident
      with a 90% fall in the atmospheric CO(2) concentration ([CO(2)](a)). Here we show
      using standardized dual isotopic tracers ((14)C and (33)P) that AM symbiosis
      efficiency (defined as plant P gain per unit of C invested into fungi) of
      liverwort gametophytes declines, but increases in the sporophytes of vascular
      plants (ferns and angiosperms), at 440 p.p.m. compared with 1,500 p.p.m.
      [CO(2)](a). These contrasting responses are associated with larger AM hyphal
      networks, and structural advances in vascular plant water-conducting systems,
      promoting P transport that enhances AM efficiency at 440 p.p.m. [CO(2)](a). Our
      results suggest that non-vascular land plants not only faced intense competition
      for light, as vascular land floras grew taller in the Palaeozoic, but also
      markedly reduced efficiency and total capture of P as [CO(2)](a) fell.

PMID- 22588298
TI  - A crucial role for bone morphogenetic protein-Smad1 signalling in the DNA damage
      response.
AB  - DNA damage and the elicited cellular response underlie the etiology of
      tumorigenesis and ageing. Yet, how this response integrates inputs from cells'
      environmental cues remains underexplored. Here we report that the BMP-Smad1
      pathway, which is essential for embryonic development and tissue homeostasis, has
      an important role in the DNA damage response and oncogenesis. On genotoxic
      stress, Atm phosphorylates BMPs-activated Smad1 in the nucleus on S239, which
      disrupts Smad1 interaction with protein phosphatase PPM1A, leading to enhanced
      activation and upregulation of Smad1. Smad1 then interacts with p53 and inhibits
      Mdm2-mediated p53 ubiquitination and degradation to regulate cell proliferation
      and survival. Enhanced Smad1 S239 phosphorylation, and Smad1 mutations causing
      S239 substitution were detected in oesophageal and gastric cancer samples,
      respectively. These findings suggest that BMP-Smad1 signalling participates in
      the DNA damage response via the Atm-p53 pathway, thus providing a molecular
      mechanism whereby BMP-Smad1 loss-of-function leads to tumorigenesis, for example,
      juvenile polyposis and Cowden syndromes.

PMID- 22588299
TI  - Developmentally based scaling of leaf venation architecture explains global
      ecological patterns.
AB  - Leaf size and venation show remarkable diversity across dicotyledons, and are key
      determinants of plant adaptation in ecosystems past and present. Here we present
      global scaling relationships of venation traits with leaf size. Across a new
      database for 485 globally distributed species, larger leaves had major veins of
      larger diameter, but lower length per leaf area, whereas minor vein traits were
      independent of leaf size. These scaling relationships allow estimation of intact
      leaf size from fragments, to improve hindcasting of past climate and biodiversity
      from fossil remains. The vein scaling relationships can be explained by a
      uniquely synthetic model for leaf anatomy and development derived from published
      data for numerous species. Vein scaling relationships can explain the global
      biogeographical trend for smaller leaves in drier areas, the greater construction
      cost of larger leaves and the ability of angiosperms to develop larger and more
      densely vascularised lamina to outcompete earlier-evolved plant lineages.

PMID- 22588300
TI  - Phase fluctuations and the absence of topological defects in a photo-excited
      charge-ordered nickelate.
AB  - The dynamics of an order parameter's amplitude and phase determines the
      collective behaviour of novel states emerging in complex materials. Time- and
      momentum-resolved pump-probe spectroscopy, by virtue of measuring material
      properties at atomic and electronic time scales out of equilibrium, can decouple
      entangled degrees of freedom by visualizing their corresponding dynamics in the
      time domain. Here we combine time-resolved femotosecond optical and resonant X
      ray diffraction measurements on charge ordered La(1.75)Sr(0.25)NiO(4) to reveal
      unforeseen photoinduced phase fluctuations of the charge order parameter. Such
      fluctuations preserve long-range order without creating topological defects,
      distinct from thermal phase fluctuations near the critical temperature in
      equilibrium. Importantly, relaxation of the phase fluctuations is found to be an
      order of magnitude slower than that of the order parameter's amplitude
      fluctuations, and thus limits charge order recovery. This new aspect of phase
      fluctuations provides a more holistic view of the phase's importance in ordering
      phenomena of quantum matter.

PMID- 22588301
TI  - Enamel-like apatite crown covering amorphous mineral in a crayfish mandible.
AB  - Carbonated hydroxyapatite is the mineral found in vertebrate bones and teeth,
      whereas invertebrates utilize calcium carbonate in their mineralized organs. In
      particular, stable amorphous calcium carbonate is found in many crustaceans. Here
      we report on an unusual, crystalline enamel-like apatite layer found in the
      mandibles of the arthropod Cherax quadricarinatus (freshwater crayfish). Despite
      their very different thermodynamic stabilities, amorphous calcium carbonate,
      amorphous calcium phosphate, calcite and fluorapatite coexist in well-defined
      functional layers in close proximity within the mandible. The softer amorphous
      minerals are found primarily in the bulk of the mandible whereas apatite, the
      harder and less soluble mineral, forms a wear-resistant, enamel-like coating of
      the molar tooth. Our findings suggest a unique case of convergent evolution,
      where similar functional challenges of mastication led to independent
      developments of structurally and mechanically similar, apatite-based layers in
      the teeth of genetically remote phyla: vertebrates and crustaceans.

PMID- 22588302
TI  - Symbiont fidelity and the origin of species in fungus-growing ants.
AB  - A major problem in evolutionary biology is explaining the success of mutualism.
      Solving this problem requires understanding the level of fidelity between
      interacting partners. Recent studies have proposed that fungus-growing ants and
      their fungal cultivars are the products of 'diffuse' coevolution, in which single
      ant and fungal species are not exclusive to one another. Here we show for ants
      and associated fungi in the Cyphomyrmex wheeleri species group that each ant
      species has been exclusively associated with a single fungal cultivar 'species'
      for millions of years, even though alternative cultivars are readily available,
      and that rare shifts to new cultivars are associated with ant speciation. Such
      long-term partner fidelity may have facilitated 'tight' ant-fungus coevolution,
      and shifts to new fungal cultivars may have had a role in the origin of new ant
      species.

PMID- 22588303
TI  - Activin induces cortical interneuron identity and differentiation in embryonic
      stem cell-derived telencephalic neural precursors.
AB  - Understanding the mechanisms underlying neural progenitor differentiation and
      neuronal fate specification is critical for the use of embryonic stem cells
      (ESCs) for regenerative medicine. Cortical interneurons are of particular
      interest for cell transplantation; however, only a limited subset of these
      neurons can be generated from ESCs. Here we uncover a pivotal role for Activin in
      regulating the differentiation and identity of telencephalic neural precursors
      derived from mouse and human ESCs. We show that Activin directly inhibits the
      mitogenic sonic hedgehog pathway in a Gli3-dependent manner while enhancing
      retinoic acid signalling, the pro-neurogenic pathway. In addition, we demonstrate
      that Activin provides telencephalic neural precursors with positional cues that
      specifically promote the acquisition of a calretinin interneuron fate by
      controlling the expression of genes that regulate cortical interneuron identity.
      This work demonstrates a novel means for regulating neuronal differentiation and
      specification of subtype identity.

PMID- 22588304
TI  - Serine-7 but not serine-5 phosphorylation primes RNA polymerase II CTD for P-TEFb
      recognition.
AB  - Phosphorylation of RNA polymerase II carboxy-terminal domain (CTD) in hepta
      repeats YSPTSPS regulates eukaryotic transcription. Whereas Ser5 is
      phosphorylated in the initiation phase, Ser2 phosphorylation marks the elongation
      state. Here we show that the positive transcription elongation factor P-TEFb is a
      Ser5 CTD kinase that is unable to create Ser2/Ser5 double phosphorylations, while
      it exhibits fourfold higher activity on a CTD substrate pre-phosphorylated at
      Ser7 compared with the consensus hepta-repeat or the YSPTSPK variant. Mass
      spectrometry reveals an equal number of phosphorylations to the number of hepta
      repeats provided, yet the mechanism of phosphorylation is distributive despite
      the repetitive nature of the substrate. Inhibition of P-TEFb activity is mediated
      by two regions in Hexim1 that act synergistically on Cdk9 and Cyclin T1. HIV-1
      Tat/TAR abrogates Hexim1 inhibition to stimulate transcription of viral genes but
      does not change the substrate specificity. Together, these results provide
      insight into the multifaceted pattern of CTD phosphorylation.

PMID- 22588305
TI  - Environmental noise exposure degrades normal listening processes.
AB  - To date, the functional and physiological impact on the mature brain of moderate
      level environmental noises that do not cause noticeable peripheral deficits
      remains largely unstudied. Here we show that exposing adult rats to structured
      noise at a sound pressure level of 65 dB, which is markedly below the broadly
      accepted safety level standard, results in behavioural impairments and
      substantially impairs the function of the auditory cortex. The strong
      deterioration in cortical processing of acoustic inputs is independent of the
      modulation rates of structured noises. Almost equally strong effects result from
      10-h daily versus 24-h daily exposure regimens. These results indicate that there
      can be substantial negative consequences for the auditory system documented at
      the cortical level, attributable to environmental exposure to structured noises
      delivered under conditions that do not directly impact hearing sensitivity. These
      noises are deemed to be 'safe' and are often present in modern human
      environments.

PMID- 22588306
TI  - Nanotomy-based production of transferable and dispersible graphene nanostructures
      of controlled shape and size.
AB  - Because of the edge states and quantum confinement, the shape and size of
      graphene nanostructures dictate their electrical, optical, magnetic and chemical
      properties. The current synthesis methods for graphene nanostructures do not
      produce large quantities of graphene nanostructures that are easily transferable
      to different substrates/solvents, do not produce graphene nanostructures of
      different and controlled shapes, or do not allow control of GN dimensions over a
      wide range (up to 100 nm). Here we report the production of graphene
      nanostructures with predetermined shapes (square, rectangle, triangle and ribbon)
      and controlled dimensions. This is achieved by diamond-edge-induced nanotomy
      (nanoscale-cutting) of graphite into graphite nanoblocks, which are then
      exfoliated. Our results show that the edges of the produced graphene
      nanostructures are straight and relatively smooth with an I(D)/I(G) of 0.22-0.28
      and roughness <1 nm. Further, thin films of GN-ribbons exhibit a bandgap
      evolution with width reduction (0, 10 and ~35 meV for 50, 25 and 15 nm,
      respectively).

PMID- 22588307
TI  - Higher rates of chronic hepatitis B infection and low vaccination-induced
      protection rates among parturients escaping HBsAg prenatal testing in Greece:  a
      2-year prospective study.
AB  - OBJECTIVES: Universal screening for the identification of hepatitis B surface
      antigen [HBsAg(+)] mothers is essential to prevent perinatal hepatitis B virus
      (HBV) infection. In Greece, although adherence to HBV prenatal testing has
      improved significantly, there are still pregnant women who do not receive
      testing, and there is concern that this group may include women with a higher
      disease burden. METHODS: The seroprevalence of HBV markers among parturient women
      escaping HBsAg prenatal testing was assessed prospectively. Seropositivity rates
      were compared with those from a control group of women [n=1304, Greek: 1156
      (88.7%), Albanian: 148 (11.3%)], with appropriate prenatal HBsAg documentation,
      who delivered in the same public hospital. RESULTS: Between January 2007 and
      March 2009, 9546 women delivered at the Alexandra Hospital, Athens, Greece, and
      1000 (10.6%, mean age: 26.6+/-6.2 years) were unable to document their HBsAg
      status. Among women tested for the first time in the delivery room, 70.4% were
      immigrants (Albanians: 41.7%, Eastern European: 14.7%, African: 7.2%, Asian:
      6.9%), 15.2% were of Roma origin, and 14.4% were Greek. Overall, 53/1000 (5.3%,
      95% confidence interval: 4.1-6.9%) HBsAg(+) cases were found (Albanians: 7.4%,
      Roma: 5.3%, Asians: 4.3%, Eastern European: 3.4%, Greeks: 2.8%, African: 2.8%,
      P<0.05 between Greek and Albanian women) versus 15/1304 (1.2%, 95% confidence
      interval: 0.7-1.9%) in the control group (P<0.0001). Greek women nonadherent to
      HBV maternal testing were more likely to be chronically infected with HBV (0.6
      vs. 2.8%, P<0.05), whereas a similar trend was observed in Albanian women (5.4
      vs. 7.4%, P=0.45). Disappointingly low vaccination-induced protection rates (mean
      21.4%) were observed among women escaping HBV maternal testing. CONCLUSION:
      Higher HBV disease burden and low vaccination-induced protection are
      characteristic in pregnant women nonadherent to HBsAg prenatal testing. More
      intense surveillance and implementation of immunization programs should be
      applied in these populations.

PMID- 22588308
TI  - Linear, nonlinear or categorical: how to treat complex associations? Splines and
      nonparametric approaches.

PMID- 22588309
TI  - Neighbourhood context and abuse among immigrant and non-immigrant women in
      Canada: findings from the Maternity Experiences Survey.
AB  - OBJECTIVES: To examine the relationship between neighbourhood deprivation and
      concentration of immigrants, and abuse among immigrant women versus non-immigrant
      women. METHODS: Using data from the Canadian Maternity Experiences Survey (un
      weighted sample N = 5,679 and weighted sample N = 68,719) linked to the
      neighbourhoods Census data, we performed contextual analysis to compare abuse
      prevalence among: immigrants <=5 years, immigrants >5 years and Canadian-born. We
      identified two level effect modifiers: living in high (<=15 % of households at or
      below low-income cut-off- [LICO]) versus low-income (>15 % below LICO)
      neighbourhoods and living in high (>=25 %) versus low immigrant (<25 %)
      neighbourhoods. Individual socioeconomic position (SEP), family variables and
      neighbourhood SEP or percentage of immigrants were considered in different
      logistic regression models. RESULTS: Immigrant women were less likely to
      experience abuse even upon adjustment for individual SEP, family variables and
      neighbourhood characteristics. The protective effect of the neighborhood was
      stronger among immigrant women living in low-income and high immigrant
      neighborhoods, irrespective of length of stay in Canada. CONCLUSION: Policies and
      interventions to reduce abuse among immigrant women need to consider
      neighbourhood's SEP and concentration of immigrants.

PMID- 22588311
TI  - Doing the best for one's child: satisficing versus optimizing parentalism.
AB  - The maxim "parents should do what is in the best interests of their child" seems
      like an unassailable truth, and yet, as I argue here, there are serious problems
      with it when it is taken seriously. One problem concerns the sort of demands such
      a principle places on parents; the other concerns its larger social implications
      when conceived as part of a national policy for the rearing of children. The
      theory of parenting that creates these problems I call "optimizing parentalism."
      To avoid them, I define and defend a new and more morally appealing theory,
      "satisficing parentalism."

PMID- 22588312
TI  - Elevation of KL-6 serum levels in clinical trials of tumor necrosis factor
      inhibitors in patients with rheumatoid arthritis: a report from the Japan College
      of Rheumatology Ad Hoc Committee for Safety of Biological DMARDs.
AB  - OBJECTIVE: The associations between elevated levels of serum Krebs von den Lungen
      6 (KL-6) and treatment of rheumatoid arthritis (RA) with tumor necrosis factor
      (TNF) inhibitors were investigated in five Japanese clinical trials. METHODS:
      Percentages and incidence rates were calculated for elevated serum KL-6 levels.
      Adverse events associated with elevated levels of serum KL-6 were investigated.
      RESULTS: In RISING, a clinical trial for infliximab, 15.6 % of the enrolled
      patients met criterion B (KL-6 >=500 U/ml and >1.5-fold increase over the
      baseline value) by week 54. In HIKARI, 7.8 % of the certolizumab pegol (CZP)
      group and 0 % of the placebo group met criterion B during the double-blind (DB)
      period (p = 0.003). In J-RAPID, 8.4 % of the methotrexate (MTX) + CZP and 3.9 %
      of the MTX + placebo groups met criterion B during the DB period. In GO-MONO, 1.8
      % of the golimumab (GLM) and 1.3 % of the placebo groups met criterion B during
      the DB period. In GO-FORTH, 7.1 % of the MTX + GLM and 0 % of the MTX + placebo
      groups met criteron B during the DB period (p = 0.017). No adverse events
      accompanied the elevation of serum KL-6 levels in 95.7 % of these patients.
      CONCLUSION: Serum KL-6 levels may increase during anti-TNF therapy without
      significant clinical events. In these patients, continuing treatment with TNF
      inhibitors under careful observation is a reasonable option.

PMID- 22588310
TI  - The embodiment of adverse childhood experiences and cancer development: potential
      biological mechanisms and pathways across the life course.
AB  - OBJECTIVES: To explore current evidence of the physiological embedding of stress
      to discuss whether adverse childhood experiences (ACE) causing chronic or acute
      stress responses may alter fundamental biological functions. METHODS: A non
      systematic review of the literature was carried out using keyword searches in
      Pubmed and the web of science from May to October 2011. In reference to the
      literature identified, we examine the potential biological pathways potentially
      linking exposure to ACE and cancer development and progression in adulthood.
      RESULTS: These mechanisms, in interaction with social position, and mediated by
      subsequent environmental exposures, may ultimately lead to the development of
      cancer. The experience of acute or chronic stressors during sensitive periods of
      childhood development which can induce several known biological responses, are
      likely to have an impact on subsequent biological and behavioural functions
      depending on the timing of initial exposures, and subsequently mediated by later
      exposures. For this reason, childhood exposure to adversity is a likely source of
      both acute and chronic stressors, and can be examined as an important initial
      exposure on a pathway towards adult ill health. CONCLUSIONS: Such pathways
      justify a life course approach to understanding cancer aetiology, which may have
      its origins early in life.

PMID- 22588314
TI  - Client satisfaction with HIV counseling services: a cross-sectional study from
      south India.
AB  - BACKGROUND: Client satisfaction is a good predictor of performance of health
      programs. Hence, clients' perception and satisfaction studies provide insight to
      improve the program. PURPOSE: To assess clients' perception and satisfaction with
      Integrated Counselling and Testing Centres (ICTCs) for HIV in an operational
      setting. METHODS: A total of 191 client exit interviews from 12 ICTCs. The
      clients were stratified into general and antenatal clients. A systematic random
      sampling was done at high client load centers. RESULTS: Cumulative client
      satisfaction was found to be 60% (+/-24%). Most of the clients (76%) agreed that
      counseling cleared doubts about HIV and found counseling beneficial (71%). Only
      32% of the clients could recall issues discussed during the sessions. However,
      92.5% were satisfied with ICTC facilities. CONCLUSIONS: Poor perception and low
      satisfaction with ICTCs needs to be addressed as this could have a direct bearing
      on the program.

PMID- 22588315
TI  - Continuous operation of a hybrid solid-liquid state reconfigurable photonic
      system without resupply of liquids.
AB  - Optofluidics offers a number of potentially transformative advantages for
      photonic systems. At present however there are a number of technological
      roadblocks that prevent the practical integration of liquid-state elements into
      traditional high-speed solid-state photonic systems. Two of the most important of
      these are the need for continuous resupply of liquids and the difficulty in
      shuttling light between the liquid- and solid-states. In this paper we present an
      integrated system that solves both these problems. For the first time we
      demonstrate direct evanescent and end-fire coupling between liquid- and solid
      state waveguides and an on-chip fluid core/cladding separation and recirculation
      system that reduces the consumption of liquids more than 200 fold over the state
      of the art. The device is operated continuously for over 20 h without performance
      degradation or requiring the replenishment of liquids. We believe that our system
      represents an important step towards the development of practical optofluidically
      enabled photonic systems.

PMID- 22588317
TI  - Fixation of carbon dioxide and related small molecules by a bifunctional
      frustrated pyrazolylborane Lewis pair.
AB  - The bifunctional frustrated Lewis pair 1-[bis(pentafluorophenyl)boryl]-3,5-di
      tert-butyl-1H-pyrazole (1) was employed for small molecule fixation by reaction
      with carbon dioxide, paraformaldehyde, tert-butyl isocyanate, tert-butyl
      isothiocyanate, methyl isothiocyanate and benzonitrile, affording the adducts 3-8
      as zwitterionic, bicyclic boraheterocycles. Treatment of 1 with tert-butyl
      isocyanide gave the isocyanide-borane complex 9, whereas the zwitterionic
      alkynylborate 10 was formed by C-H bond activation of phenylacetylene. The
      molecular structures of all products 3-10 were established by X-ray diffraction
      analyses. DFT calculations at the M06-2X/6-311++G(d,p) level of theory revealed
      that CO(2) fixation by 1 and formation of the adduct 3 is strongly exothermic and
      proceeds with a low energy barrier of approximately 7.3 kcal mol(-1) via an
      intermediate van der Waals complex.

PMID- 22588316
TI  - Very important pharmacogene summary for VDR.

PMID- 22588318
TI  - Heart failure: can we define, assess, and treat diastolic heart failure?

PMID- 22588319
TI  - Tailored telemonitoring in patients with heart failure: results of a multicentre
      randomized controlled trial.
AB  - AIMS: Recent increases in heart failure tend to overload the healthcare system.
      Consequently, there is a need for innovative strategies to reduce heart failure
      hospitalizations. METHODS AND RESULTS: A multicentre randomized controlled trial
      was carried out to test the hypothesis that telemonitoring reduces heart failure
      hospitalizations during 1 year follow-up. The mean age of the 382 participating
      patients was 71.5 (32-93) years; the mean left ventricular ejection fraction was
      0.38, and in 61% it was <=0.45%. Mean time to first heart failure-related
      hospitalization was 161 days for the intervention group and 139 days for the
      usual-care group; hospitalizations occurred in 18 (9.1%) compared with 25 (13.5%)
      patients, with a total number of 24 and 43 hospitalizations, respectively [Kaplan
      Meier P = 0.151, hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.35-1.17].
      Subgroup analysis of the primary endpoint showed benefits for three subgroups:
      duration of heart failure, having a pacemaker, and co-habiting. The combined
      endpoint of heart failure admission and all-cause mortality was similar for both
      groups (Kaplan-Meier P = 0.641, HR 0.89, 95% CI 0.69-1.83). No differences were
      found regarding secondary endpoints, except for the reduced number of face to
      face contacts with the heart failure nurse (Mann-Whitney P < 0.001). Mortality
      was 18 (9.1%) in the intervention group and 12 (6.5%) in the usual-care group
      (Mann-Whitney P = 0.34, Cox regression analysis P = 0.82). CONCLUSION: No
      significant differences were found regarding the primary endpoint, possibly
      caused by a relative underpowering of the population combined with well-treated
      study groups. However, telemonitoring tends to reduce heart failure
      (re)admissions and significantly decreases contacts with specialized nurses.
      Further research with pre-specified groups, as found in the subgroup analysis, is
      needed. TRIAL REGISTRATION: NCT00502255.

PMID- 22588320
TI  - Increased Rho kinase activity in congestive heart failure.
AB  - AIMS: Rho kinases (ROCKs) are the best characterized effectors of the small G
      protein RhoA, and play a role in enhanced vasoconstriction in animal models of
      congestive heart failure (CHF). This study examined if ROCK activity is increased
      in CHF and how it is associated with the outcome in CHF. METHODS AND RESULTS:
      Patients admitted with CHF (n =178), disease controls (n =31), and normal
      subjects (n =30) were studied. Baseline ROCK activity was measured by
      phosphorylation of themyosin-binding subunit in peripheral leucocytes. The
      patients were followed up for 14.4 +/- 7.2 months (range 0.5-26 months) or until
      the occurrence of cardiac death. The ROCK activity in CHF patients (2.93 +/-
      0.87) was significantly higher than that of the disease control (2.06 +/- 0.38, P
      < 0.001) and normal control (1.57 +/- 0.43, P < 0.001) groups. Similarly, protein
      levels of ROCK1 and ROCK2 as well as the activity of RhoA in CHF were
      significantly higher than in disease controls and normal controls (all P < 0.05).
      Dyspnoea at rest (beta =0.338, P < 0.001), low left ventricular ejection fraction
      (beta = -0.277, P < 0.001), and high creatinine (beta =0.202, P =0.006) were
      independent predictors of the baseline ROCK activity in CHF. Forty-five patients
      died within 2 years follow-up (25.3%). Combining ROCK activity and N-terminal pro
      brain natriuretic peptide (NT-proBNP) had an incremental value (log rank chi(2)
      =11.62) in predicting long-term mortality when compared with only NT-proBNP (log
      rank chi(2) =5.16, P < 0.05). CONCLUSION: ROCK activity is increased in CHF and
      it might be associated with the mortality in CHF. ROCK activity might be a
      complementary biomarker to CHF risk stratification.

PMID- 22588321
TI  - Delayed recovery in peripartum cardiomyopathy: an indication for long-term follow
      up and sustained therapy.
AB  - AIMS: Persistence of left ventricular (LV) systolic dysfunction after 6 months of
      diagnosis is believed to be a marker of an irreversible cardiomyopathy in
      peripartum cardiomyopathy (PPCM). We sought to determine the length of time
      required for recovery of LV systolic function (LVSF) in patients with PPCM.
      METHODS AND RESULTS: Forty-two consecutive women with PPCM were enrolled in this
      prospective study. The minimum required time of follow-up for inclusion was 30
      months. Each patient underwent transthoracic echocardiography, and plasma brain
      natriuretic peptide (BNP) and C-reactive protein measurement at admission, and
      every 3 months. Early recovery was defined as normalization of LVSF at 6 months
      post-diagnosis. Delayed recovery was defined if the length of time required for
      recovery of LVSF was longer than 6 months. Persistent left ventricular
      dysfunction (PLVD) was defined as an ejection fraction of <50% at the end of
      follow-up. Twenty patients (47.6%) recovered completely, 10 died (23.8%), and 12
      (28.6%) had PLVD. Average time to complete recovery was 19.3 months after initial
      diagnosis (3-42 months). Early recovery was observed only in six patients (30%),
      whereas delayed recovery was observed in 14 out of 20 patients (70%). Patients
      with complete recovery were more likely to have a higher LV ejection fraction and
      smaller LV end-systolic dimensions at baseline. CONCLUSION: Full recovery of LVSF
      in PPCM patients often requires longer than 6 months.

PMID- 22588322
TI  - Acute effect of percutaneous MitraClip therapy in patients with haemodynamic
      decompensation.
AB  - AIMS: To evaluate the haemodynamic effect of acute procedural success (APS) after
      MitraClip therapy in patients with haemodynamic decompensation. METHODS AND
      RESULTS: Of 107 patients, 79 achieved APS after MitraClip implantation. The
      increase in cardiac index (CI) was primarily detected in patients with a low
      baseline CI (2.0 +/- 0.5 to 2.5 +/- 5 L/min/m(2), P < 0.001). There was a
      decrease in left ventricular end-diastolic pressure (LVEDP) (20 +/- 5 to 13 +/- 5
      mmHg, P = 0.002) and mean pulmonary capillary wedge pressure (PCWPm) (20 +/- 4 to
      16 +/- 5 mmHg, P = 0.001) in patients with values >15 mmHg at baseline, and a
      decrease in mean pulmonary artery systolic (PAPm) (36 +/- 4 to 29 +/- 7 mmHg P =
      0.003) in those with values >30 mmHg before the MitraClip procedure. Patients
      with decompensation compared with patients with compensation experienced
      significant reduction in LVEDP (-8.3 +/- 11.9 mmHg vs. -0.2 +/- 4.5 mmHg, P =
      0.009), a reduction in PCWPm (-3.5 +/- 5.6 mmHg vs. 1.9 +/- 4.7 mmHg, P < 0.001),
      and a reduction in PAPm (-8 +/- 9 mmHg vs. 3 +/- 6 mmHg, P < 0.001). CONCLUSION:
      The favourable haemodynamic effects of MitraClip therapy on CI were primarily
      detected in patients with low CI before the procedure, and improvements in left
      sided filling pressure and PAP were primarily seen in those with elevated values
      at baseline.

PMID- 22588323
TI  - Social isolation, vital exhaustion, and incident heart failure: findings from the
      Atherosclerosis Risk in Communities Study.
AB  - AIMS: Prospective studies have shown that social isolation (i.e. lack of social
      contacts) predicts incident coronary heart disease (CHD), but it is unclear
      whether it predicts incident heart failure (HF) and what factors might mediate
      this association. HF patients may be more susceptible to social isolation as they
      tend to be older and may have disrupted social relationships due to life course
      factors (e.g. retirement or bereavement). We prospectively examined whether
      individuals with higher vs. low social isolation have a higher incidence of HF
      and determined whether this association is mediated by vital exhaustion. METHODS
      AND RESULTS: We estimated incident HF hospitalization or death among 14 348
      participants from Visit 2 (1990-1992) in the Atherosclerosis Risk in Communities
      (ARIC) study using Cox proportional hazard models which were sequentially
      adjusted for age, race/study community, gender, current smoking, alcohol use, and
      co-morbidities. We conducted mediation analyses according to the Baron and Kenny
      method. After a median follow-up of 16.9 person-years, 1727 (13.0%) incident HF
      events occurred. The adjusted hazard of incident HF was greater for those in the
      higher vs. low social isolation risk group (hazard ratio 1.21, 95% confidence
      interval 1.08-1.35). Our data suggest that vital exhaustion strongly mediates the
      association between higher social isolation and incident HF (the percentage
      change in beta coefficient for higher vs. low social isolation groups after
      adjusting for vital exhaustion was 36%). CONCLUSION: These data suggest that
      greater social isolation is an independent risk factor for incident HF, and this
      association appears to be strongly mediated by vital exhaustion.

PMID- 22588324
TI  - The ratio of the absolute lymphocyte count to the absolute monocyte count is
      associated with prognosis in Hodgkin's lymphoma: correlation with tumor
      associated macrophages.
AB  - BACKGROUND: Although most patients with classical Hodgkin's lymphoma (cHL) have a
      long survival duration, the current risk stratification is imperfect. A recent
      study suggested a prognostic role for the peripheral blood absolute lymphocyte
      count/absolute monocyte count (ALC/AMC) ratio at diagnosis in cHL. It is
      intriguing to investigate the significance of the ALC/AMC ratio in relation to
      tumor-associated macrophages (TAMs), yet another prognostic factor for cHL.
      METHODS: We examined the prognostic impact of the ALC, AMC, and ALC/AMC ratio in
      312 cHL patients (median age, 37 years) using receiver operating characteristic
      curve analysis for optimal cutoff values, and compared these with TAM content.
      RESULTS: The median follow-up was 65 months (range, 0.1-245 months). On
      univariate analysis, a low ALC/AMC ratio (<2.9) was correlated with a poorer
      overall survival (OS) outcome. A subgroup analysis of patients with limited-stage
      disease showed that the ALC/AMC ratio was significantly correlated with the OS
      time. Multivariate analysis showed the ALC/AMC ratio to be an independent
      prognostic factor for OS outcome. A Spearman correlation test of TAM content
      showed a negative correlation with the ALC/AMC ratio and a positive correlation
      with the peripheral blood macrophage percentage. CONCLUSIONS: This study suggests
      that the ALC/AMC ratio may be a simple, inexpensive, and independent prognostic
      factor for OS outcome in patients with cHL and may have a role in the
      stratification of cHL patients in addition to the International Prognostic Score
      and TAM content.

PMID- 22588326
TI  - A novel frameshift mutation Gly239Serfs*8 in the PROC gene results in protein C
      deficiency in a Korean patient.

PMID- 22588325
TI  - Risk, characteristics, and prognosis of breast cancer after Hodgkin's lymphoma.
AB  - PURPOSE: To assess breast cancer (BC) risk after Hodgkin's lymphoma (HL) and
      compare characteristics, risk of second BC, and prognosis of patients with these
      BCs with patients with first primary BC. PATIENTS AND METHODS: We considered all
      9,620 women with HL recorded in the Surveillance, Epidemiology and End Results
      dataset in 1973-2007. We calculated age-period standardized incidence ratios of
      BC. We compared patient, tumor, and treatment characteristics, risk of second BC,
      and prognosis between patients with BC after HL (n = 316) and patients with other
      BCs occurring during the same period (n = 450,413) using logistic regression and
      Cox models adjusted for confounders. RESULTS: HL patients had a 2.4-fold higher
      risk for developing BC (95% confidence interval [CI], 2.2-2.7) than the general
      population. Age at HL diagnosis and radiation therapy influenced this risk.
      Compared with first primary BCs, BCs after HL were diagnosed at a younger age, at
      an earlier stage, were less frequently hormone receptor positive, were located
      more frequently in external quadrants, and were less frequently treated using
      radiotherapy. These patients had a higher risk (adjusted hazard ratio [HR], 2.85;
      95% CI, 1.79-4.53) for developing a second BC and had a higher BC mortality risk
      (adjusted HR, 1.36; 95% CI, 1.05-1.76). The higher mortality risk was only partly
      explained by the higher occurrence rate of a second BC. CONCLUSION: HL survivors
      have a higher risk for developing BC, their BCs are more aggressive, they have a
      higher risk for a second BC occurrence, and they have a poorer prognosis.
      Guidelines of care should be adapted to decrease the impact of BC in these high
      risk patients.

PMID- 22588327
TI  - Deep vein thrombosis associated with factor V inhibitor followed by immune
      thrombocytopenia.

PMID- 22588328
TI  - Metabolic factors and blood cancers among 578,000 adults in the metabolic
      syndrome and cancer project (Me-Can).
AB  - We investigated associations between metabolic factors and blood cancer subtypes.
      Data on body mass index (BMI), blood pressure, blood glucose, total cholesterol,
      and triglycerides from seven prospective cohorts were pooled (n = 578,700; mean
      age = 44 years). Relative risks of blood cancers were calculated from Cox
      regression models. During mean follow-up of 12 years, 2,751 incident and 1,070
      fatal cases of blood cancers occurred. Overall, higher BMI was associated with an
      increased blood cancer risk. In gender-specific subgroup analyses, BMI was
      positively associated with blood cancer risk (p = 0.002), lymphoid neoplasms (p =
      0.01), and Hodgkin's lymphoma (p = 0.02) in women. Further associations with BMI
      were found for high-grade B-cell lymphoma (p = 0.02) and chronic lymphatic
      leukemia in men (p = 0.05) and women (p = 0.01). Higher cholesterol levels were
      inversely associated with myeloid neoplasms in women (p = 0.01), particularly
      acute myeloid leukemia (p = 0.003), and glucose was positively associated with
      chronic myeloid leukemia in women (p = 0.03). In men, glucose was positively
      associated with risk of high-grade B-cell lymphoma and multiple myeloma, while
      cholesterol was inversely associated with low-grade B-cell lymphoma. The
      metabolic syndrome score was related to 48 % increased risk of Hodgkin's lymphoma
      among women. BMI showed up as the most consistent risk factor, particularly in
      women. A clear pattern was not found for other metabolic factors.

PMID- 22588329
TI  - Neuroprotective effects of pretreatment with propofol in LPS-induced BV-2
      microglia cells: role of TLR4 and GSK-3beta.
AB  - Surgery often leads to neuroinflammation, which mainly acts as the activation of
      microglia cells. Propofol is always used for induction and maintenance of
      anesthesia prior to surgical trauma, whereas whether or not it could attenuate
      neuroinflammation used prophylactically is not well defined. In the present
      study, we incubated BV-2 microglia cells with 1 MUg/ml lipopolysaccharide (LPS)
      to mimic neuroinflammation in vitro. Firstly, cell viability was measured using 3
      (4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and the
      data indicated that propofol would not reduce cell viability unless its
      concentration reached 300 MUM. Secondly, BV-2 microglia cells were pretreated
      with 30 MUM propofol (clinically relevant concentration), and then stimulated
      with LPS. The results showed that the production of tumor necrosis factor-alpha
      (TNF-alpha), interleukin (IL)-1beta and IL-10 was considerably increased by LPS,
      but the change could be markedly attenuated by pretreatment with propofol.
      Meanwhile, pretreatment with propofol inhibited LPS-induced augmentation of toll
      like receptor 4 (TLR4) expression at both mRNA and protein levels and further
      upregulated LPS-induced inactivation of glycogen synthase kinase-3beta (GSK
      3beta) in BV-2 microglia cells. These results indicated, at least in part, that
      pretreatment with propofol can protect BV-2 microglia cells against LPS-induced
      inflammation. Downregulation of TLR4 expression and inactivation of GSK-3beta may
      be involved in its protective effect.

PMID- 22588331
TI  - Adjusting to mealtime change within the context of dementia.
AB  - Little is known about how persons with dementia and their care partners respond
      to mealtime changes that occur throughout the dementia journey. By interviewing
      27 persons living with dementia and their 28 care partners, we explored the
      meaning and experience of change surrounding mealtimes. Participants adjusted to
      mealtime change by adapting to an evolving life, as a result of a dynamic process
      of becoming aware of change, attaching meaning to change, and responding to
      change. Seminal events compounded by a sense of things being different triggered
      awareness of mealtime changes. Meaning was attached to mealtime changes, observed
      through emotions experienced and diverse strategies developed to support mealtime
      values. Responding to change ranged from resisting, to being in a holding
      pattern, to transforming and adapting. Understanding how individuals and families
      adjust to mealtime changes, and the strategies they develop, provides critical
      insights for supporting families throughout the dementia journey.

PMID- 22588330
TI  - Dichloromethane fraction of Laminaria japonica ethanolic extract inhibits
      lipopolysaccharide-induced nitric oxide synthase and cyclooxygenase-2 expression
      in RAW 264.7 cells via NF-kappaB pathway.
AB  - Strong anti-inflammatory activity has been found in Laminaria japonica
      dichloromethane fraction (LDF); however, the molecular mechanisms underlying its
      anti-inflammatory activity are not reported. Our results indicated that LDF
      inhibited LPS-induced nitric oxide and prostaglandin E(2) production in a dose
      dependent manner and suppressed the expression of inducible nitric oxide synthase
      (iNOS) and cyclooxygenase 2 (COX-2) in RAW 264.7 cells. Also, levels of pro
      inflammatory cytokines such as tumor necrosis factor-alpha, interleukin (IL)
      1beta and IL-6 were remarkably reduced by LDF in LPS-treated RAW 264.7 cells. LDF
      greatly inhibited promoter activity of nuclear factor-kappaB (NF-kappaB) and
      translocation of NF-kappaB subunits by prevention of the degradation of inhibitor
      kappaB-alpha in LPS-treated RAW 264.7 cells (p < 0.05). Moreover, LDF inhibited
      activation of mitogen-activated protein kinases and AKT in LPS-treated RAW 264.7
      cells. These results indicate that the LDF downregulates iNOS and COX-2
      expressions through the suppression of NF-kappaB pathway associated with
      inhibition of multiple signaling proteins.

PMID- 22588332
TI  - Silver nanoparticle-DNA bionanoconjugates bearing a discrete number of DNA
      ligands.
AB  - Silver nanoparticles (AgNPs), which are stable in strongly ionic solutions and
      appear as a single sharp band during gel electrophoresis, are synthesized by a
      facile one-pot process, allowing for the first time realization of AgNP-DNA bio
      nano-conjugates bearing a discrete number of DNA ligands.

PMID- 22588333
TI  - Fibrin tissue adhesive reduces postoperative blood loss in total knee
      arthroplasty.
AB  - BACKGROUND: Blood transfusion is often required in total knee replacement;
      various methods of blood preservation have been studied. The best solution is to
      reduce the loss of blood during and after surgery. MATERIALS AND METHODS: We
      designed this study to evaluate the hemostatic efficacy and safety of fibrin
      tissue adhesive (Quixil) in patients receiving total knee arthroplasty [low
      contact stress (LCS, DePuy, Warsaw, IN, US) cementless total knee replacement
      (TKR)] with a prospective, randomized, standard treatment controlled study.
      Thirty-five patients were randomized to receive treatment with fibrin tissue
      adhesive (treatment group), and 35 were randomized to be managed with
      postoperative blood recovery and reinfusion (control group). Blood loss in
      suction drain, decrease in hemoglobin values, and transfusions were recorded.
      RESULTS: A significant reduction in apparent total blood loss was detected in the
      treatment group compared with the control group. There was also a lower decrease
      in hemoglobin level, although this difference was not significant. When fibrin
      tissue adhesive was administered, the need for transfusions was lower. No major
      adverse events were recorded in our series. CONCLUSIONS: Fibrin tissue adhesive
      reduced blood loss in TKR and seemed to significantly reduce the need for blood
      transfusion. Fibrin tissue adhesive can be an appropriate solution to enhance
      hemostasis and vessel sealing at the operative site in TKR, in order to reduce
      blood loss after surgery and the risk of complications.

PMID- 22588334
TI  - Analysis of differential gene expression in plurihormonal pituitary adenomas
      using bead-based fiber-optic arrays.
AB  - Plurihormonal pituitary adenomas (PHPAs) are defined as those pituitary adenomas
      secreting two or more hormones that differ in chemical composition,
      immunoreactivity, and biologic effects. Since the pathogenesis of these adenomas
      is not well understood, our study aimed to explore mechanisms underlying the
      pathogenesis of PHPAs. We used bead-based fiber-optic arrays (Illumina Human
      GeneChip WG-6 v3.0) to examine the gene expression profiles in seven PHPAs
      compared with three normal pituitary glands. Four differentially expressed genes
      were chosen randomly for validation by quantitative real-time reverse
      transcription polymerase chain reaction. We then performed pathway analysis of
      all differentially expressed genes using the Kyoto Encyclopedia of Genes and
      Genomes. Our array analysis showed significant increases in the expression of 6
      genes and decreases in 334 genes and 15 expressed sequence tags in the PHPAs.
      Bioinformatic analysis showed that genes HIGD1B, EPS8, ECT2, and BTG2 might play
      an important role in the tumorigenesis and progression of PHPAs. Pathway analysis
      showed that the p53 and Notch signaling pathways may play an important role in
      tumorigenesis and progression of PHPAs, and extracellular matrix (ECM)-receptor
      interactions likely play a role in the inhibition of invasion and metastasis in
      these tumors. Our data suggested that there are numerous aberrantly expressed
      genes and pathways involved in the pathogenesis of PHPAs. Bead-based fiber-optic
      arrays combined with pathway analysis of gene expression data appears to be a
      valid method for investigating the pathogenesis of tumors.

PMID- 22588335
TI  - Potential risk factors for incident glioblastoma multiforme: the Honolulu Heart
      Program and Honolulu-Asia Aging Study.
AB  - Glioblastoma multiforme (GBM) is the most common adult primary malignant brain
      tumor. Ninety percent of adult GBM patients die within 24 months after diagnosis.
      The etiology of GBM is unknown. The Honolulu Heart Program (HHP) and Honolulu
      Asia Aging Study (HAAS) are prospective, cohort studies of cardiovascular and
      neurodegenerative disease based on 8,006 Japanese-American men followed since
      1965. The Japan Hawaii Cancer Study provides data on incident cancer cases in the
      HHP/HAAS cohort. We used data from these studies to obtain epidemiologic
      information about GBM. GBM cases were identified by searching the 1965-1998
      databases using International Classification of Diseases (ICD-9) codes. Nine
      histologically confirmed GBM cases, 58-80 years old, were identified. The
      incidence rate was 6.2/100,000 person-years. Records of each case were reviewed.
      Selected variables from the first three examinations (1965-1968; 1968-1970; 1971
      1974) were used to identify potential candidate GBM risk factors. A multivariate
      Cox proportional hazards model showed sugar intake and occupational exposure to
      carbon tetrachloride were independently and significantly associated with
      development of GBM.

PMID- 22588336
TI  - Uncertainty, misunderstanding and the pedunculopontine nucleus: the exhumation of
      an already buried dispute.

PMID- 22588337
TI  - Spinal cord herniation: management and outcome.

PMID- 22588338
TI  - Gamma knife surgery for brain metastases from ovarian cancer.
AB  - BACKGROUND: Brain metastases from ovarian cancer are rare, but their incidence is
      increasing. The purpose of this study was to investigate the characteristics of
      brain metastases from ovarian cancer, and to assess the efficacy of treatment
      with gamma knife surgery (GKS). METHODS: A retrospective review was performed of
      patients with brain metastases from ovarian cancer who were treated at the Tokyo
      Gamma Unit Center from 2006 to 2010. RESULTS: Sixteen patients were identified.
      Their median age at diagnosis of brain metastases was 56.5 years, the median
      interval from diagnosis of ovarian cancer to brain metastases was 27.5 months,
      and the median number of brain metastases was 2. The median Karnofsky Performance
      Score (KPS) at the first GKS was 80. The median survival following diagnosis of
      brain metastases was 12.5 months, and 6-month and 1-year survival rates were 75 %
      and 50 %, respectively. The tumor control rate was 86.4 %. The KPS (<80 vs >=80)
      and total volume of brain metastases (<10 cm(3) vs >=10 cm(3)) were significantly
      associated with survival according to a univariate analysis (p = 0.004 and p =
      0.02, respectively). CONCLUSIONS: The results of this study suggest that GKS is
      an effective remedy and acceptable choice for the control of brain metastases
      from ovarian cancer.

PMID- 22588340
TI  - Endoscopic septostomy through a standard precoronal ventricular access:
      feasibility and effectiveness.
AB  - BACKGROUND: Although endoscopic septostomy is widely adopted in the treatment of
      unilateral or specific types of hydrocephalus, there is no consensus on surgical
      indications, technical aspects and postoperative outcome. In particular, the
      choice of the ventricular access has been recently debated. We investigated the
      results of endoscopic septostomy performed through a standard precoronal
      ventricular access using a rigid endoscope. METHODS: Patients who underwent an
      endoscopic septostomy at our Institution from March 2001 to March 2011 were
      retrospectively identified. Clinico-radiological data and video recordings of the
      endoscopic procedures were reviewed. RESULTS: Sixty-three patients (50 children
      and 13 adults) were collected. In adults, the obstruction of the cerebrospinal
      fluid (CSF) pathway was exclusively secondary to a tumor (neoplastic or
      pseudoneoplastic lesion). In the pediatric group hydrocephalus was most commonly
      due to a neoplasm (33 out of 50 patients), post-hemorrhagic and/or post
      infectious hydrocephalus affecting 11 children and malformative hydrocephalus the
      remaining six children. We were able to perform the septostomy in all but two
      patients, presenting with a scarred multilayered septum secondary to post
      hemorrhagic hydrocephalus. In 37 cases, one or more other endoscopic procedures
      were performed contemporarily. The mean follow-up was 24 months (min-max: 5-96
      months). Overall, all but one patient benefited clinically and radiologically
      from the endoscopic septostomy. Two patients harboring a pineal/mesencephalic
      tumor experienced a late obstruction of the stoma secondary to neoplastic
      infiltration of the septum. CONCLUSIONS: Endoscopic septostomy can be safely
      performed through a standard burr-hole. The effectiveness of this approach is
      testified by an early success rate of more than 95% and a long term success rate
      of 92%.

PMID- 22588339
TI  - Clinical outcome of instrumented fusion for the treatment of failed back surgery
      syndrome: a case series of 100 patients.
AB  - OBJECT: Failed back surgery syndrome is defined as persistent chronic low-back
      pain and/or leg pain lasting more than 1 year, despite of one or more surgical
      procedures. Instrumented spinal fusion has been offered by surgeons as a
      potential treatment to recover from pain and functional disability. Factors
      contributing to good outcome of instrumented spinal fusion have not been
      investigated extensively. This study evaluated the global perceived recovery and
      functional status of patients after instrumented fusion for the treatment of
      failed back surgery syndrome. METHODS: Between January 2004 and September 2007,
      100 patients underwent instrumented spinal fusion because of persistent back
      and/or leg pain lasting more than 1 year despite of one or more previous spine
      surgeries. The global perceived recovery of the patients was documented on a
      seven-point Likert scale, in which good outcome was defined as "complete
      recovery" and "almost complete recovery". Pain was evaluated by the 100-mm visual
      analogue scale (VAS) of back pain and leg pain, and functional disability
      measured by the Roland Disability Questionnaire for Sciatica (RDQ) and Oswestry
      Disability Index (ODI). The Hospital Anxiety and Depression Scale (HADS)
      evaluated psychological co-morbidity. All patients were sent questionnaires by
      mail. Pearson's correlation coefficient was calculated between outcome measures
      and preoperative patient characteristics. RESULTS: Eighty-two patients (82%
      response rate) returned questionnaires that were useful for analysis. After a
      mean follow-up period of 15 months, 35% of the patients reported good outcome,
      whereas 65% had unsatisfactory outcome. The mean (+/- SD) score of VAS low-back
      pain and leg pain was 45.7 +/- 29 and 37.9 +/- 31.9, respectively. The mean (+/-
      SD) RDQ and ODI score was 11.8 +/- 5.4 and 30.6 +/- 20.3, respectively. HADS
      score indicated a possible anxiety disorder in 28% of the patients and in 30% a
      possible underlying depression. Of the patients' baseline characteristics, there
      was only a significantly negative correlation between level of education and
      outcome. CONCLUSIONS: The present study showed disappointing outcome of
      instrumented fusion for the treatment of failed back surgery syndrome in terms of
      perceived recovery, functional disability and pain. Conservative management is
      probably more beneficial and, therefore, more selective and careful assessment
      should be done in order to prevent unnecessary surgery.

PMID- 22588341
TI  - Vasospasm after spontaneous angiographically negative subarachnoid hemorrhage.
AB  - BACKGROUND: Vasospasm, delayed infarcts and clinical deterioration due to delayed
      cerebral ischemia (CD-DCI) following digital subtraction angiography (DSA)
      negative, spontaneous subarachnoid hemorrhage (SAH) are infrequently and
      inconsistently described in the literature. METHODS: To quantify and characterize
      rates of each, we reviewed our own series of 77 patients with DSA-negative,
      spontaneous SAH. Employing a PubMed search, we reviewed the literature and
      calculated directly adjusted overall rates of vasospasm, delayed infarcts and CD
      DCI. RESULTS: In our own patient cohort, 26 % of patients suffered vasospasm, 4 %
      delayed infarcts and 4 % CD-DCI. Higher Hunt-Hess grade and diffuse SAH pattern
      were associated with higher rates of each. Incorporating results from 18 studies
      in the literature, the directly adjusted overall rate of vasospasm following DSA
      negative SAH was 16.3 % (95 % CI 12.3-21.1). Adjusted overall rates of delayed
      infarcts and CD-DCI were 3.4 % (95 % CI 1.9-5.5) and 6.8 % (95 % CI 5.0-9.1),
      respectively. For the subgroup of patients with diffuse SAH, the rates of
      vasospasm and CD-DCI were 31.3 % (95 % CI 21.6-43.9) and 9.7 % (95 % CI 7.0
      13.0), respectively, while in patients with perimesencephalic SAH, respective
      rates were 13.1 % (95 % CI 7.7-20.7) and 2.4 % (95 % CI 1.0-4.8). A mixed-effects
      meta-analysis revealed an odds ratio for CD-DCI in diffuse SAH compared to
      perimesencephalic SAH of 3.79 (p = 0.009). CONCLUSION: Although they are seen
      less frequently in patients with DSA-negative spontaneous SAH, vasospasm, delayed
      infarcts and CD-DCI do occur and may require endovascular therapy. Risk factors
      include a diffuse hemorrhage pattern and higher Hunt-Hess grade.

PMID- 22588342
TI  - Ruptured aneurysm arising from the corkscrew basilar artery.

PMID- 22588343
TI  - A meta-analysis of the relationship between NAT2 polymorphism and colorectal
      cancer susceptibility.
AB  - BACKGROUND AND OBJECTIVE: Although the association between N-acetyltransferase 2
      (NAT2) polymorphism and colorectal cancer (CRC) susceptibility in humans has been
      extensively investigated, the results are contradictory. The aim of this study
      was to conduct a meta-analysis of published studies to quantitatively summarize
      the association between NAT2 polymorphism and risk of CRC. MATERIAL AND METHODS:
      Relevant studies that had investigated NAT2 polymorphism and CRC susceptibility
      were identified through a comprehensive search of Pubmed, EMBASE, Medline,
      Biosis, Wiley-Blackwell, ISI Web of Knowledge, CNKI, and Chinese Biomedicine
      Database until October 2011. After selection based on the inclusion and exclusion
      criteria, the relevant data were extracted from each study, and finally a meta
      analysis was performed. RESULTS: Eight phenotype studies (791 cases and 1158
      controls) and 45 genotype studies (13 875 cases and 18 879 controls) were
      included in the present meta-analysis. The pooling of phenotype studies showed no
      significant association between the NAT2 acetylator status and CRC susceptibility
      (rapid acetylator, OR, 1.32; 95% CI, 0.92-1.89, P=0.14; slow acetylator, OR,
      0.76; 95% CI, 0.53-1.09, P=0.14). The combined ORs for rapid and slow acetylator
      status and CRC risk in genotype studies were 1.01 (95% CI, 0.94-1.08; P=0.86) and
      0.99 (95% CI, 0.93-1.06; P=0.86), respectively. In the subgroup analysis by
      regions, no increased risks were found in Asians, Europeans, Americans, or
      Australasians. Pooling studies were also conducted on the groups of gender,
      specific tumor sites, and smoking status, but no significant association in
      genotype distribution between CRC and control was found as well. CONCLUSIONS:
      These results of our meta-analysis suggest that there is no overall association
      between NAT2 polymorphism and CRC susceptibility.

PMID- 22588344
TI  - Differentiation of acute myocarditis and acute myocardial infarction by the
      regional distribution of myocardial irreversible injury using cardiovascular
      magnetic resonance imaging.
AB  - BACKGROUND AND OBJECTIVE: In this study, we have sought for differences between
      cardiovascular magnetic resonance patterns of acute myocarditis and acute
      myocardial infarction. MATERIAL AND METHODS: A prospective analysis of 110
      consecutive patients was performed. The presence, precise location, and pattern
      of late gadolinium enhancement (LGE) by cardiovascular magnetic resonance were
      investigated. RESULTS: The subendocardial LGE pattern was much more frequent in
      the myocardial infarction group (76.7%) than myocarditis group (10.0%) (P<0.001).
      Meanwhile, midmyocardial LGE was much more typical of myocarditis (65.0%) than
      acute myocardial infarction (1.1%) (P<0.001), and epicardial LGE was also much
      more typical of myocarditis (55.0%) than acute myocardial infarction (0.0%)
      (P<0.001). Midmyocardial and epicardial LGE patterns were defined as a
      nonischemic LGE pattern more typical of myocarditis. Logistic regression analysis
      revealed that the subendocardial and midmyocardial LGE locations played the
      greatest role in differentiation between acute myocarditis and acute myocardial
      infarction. A statistical model based on midmyocardial LGE distribution and age
      showed a sensitivity of 90% and a specificity of 93.3% in differentiating between
      acute myocarditis and acute myocardial infarction. CONCLUSION: Our findings
      suggest that in clinical practice, differentiation between acute myocardial
      infarction and acute myocarditis can be done based on the subendocardial and
      midmyocardial LGE location. The presence of subendocardial LGE was found to be
      strongly associated with acute myocardial infarction; meanwhile, the presence of
      midmyocardial LGE indicated acute myocarditis. However, other clinical factors
      should also be taken into account when making the final diagnosis.

PMID- 22588345
TI  - Referral pattern, management, and long-term results of laparoscopic bile duct
      injuries: a case series of 44 patients.
AB  - BACKGROUND AND OBJECTIVE: The incidence of bile duct injuries (BDIs) after
      laparoscopic cholecystectomy (LC) is higher than after open cholecystectomy, and
      the management of these lesions is still controversial. This study analyzed
      diagnostic and management strategies as well as long-term outcomes after BDI.
      MATERIAL AND METHODS: A prospective database of patients with BDIs at the Clinic
      of Surgery was maintained during the 8-year period (2000-2007). The long-term
      results were evaluated during 2008-2010, after 36- to 120-month follow-up
      (median, 84 months). RESULTS: In our series, 21 patients (48%) presented with
      minor and 23 (52%) with major BDIs. The overall incidence of BDIs was 0.24%. In
      92% of cases in the minor BDI group, endoscopic stenting resulted in a good
      outcome. Major BDIs were treated by immediate, early, or delayed surgery
      depending on the timeliness of diagnosis and presence of biliary sepsis and/or
      cholangitis. The mean estimated time to failure after the initial treatment in
      the minor BDI group was significantly longer when compared with the major BDI
      group (114.3 vs. 81.8 months, log-rank test P=0.048). The hazard ratio of initial
      treatment failure after major versus minor BDIs was 6.06 (95% CI, 1.01-17.59).
      The mean estimated time to develop a biliary stricture after immediate, early,
      and delayed reconstructions was not different (P>0.05 in pairwise comparisons by
      log-rank test). CONCLUSIONS: Minor BDIs are best served by endoscopy, while
      surgical repair may be an efficient option when injury is diagnosed
      intraoperatively. The timing of reconstruction after major BDIs does not portend
      a different outcome; consequently, every attempt to achieve infection control
      should be warranted. Referral to a tertiary care center should be encouraged to
      facilitate a proper classification of preoperative injuries and multidisciplinary
      approach.

PMID- 22588346
TI  - Mortality after femoral neck fractures: a two-year follow-up.
AB  - BACKGROUND AND OBJECTIVE: To identify the survival and standardized mortality
      ratio with respect to gender, age, and treatment method of patients treated for
      femoral neck fractures. MATERIAL AND METHODS: A retrospective review of medical
      records of 736 patients treated for femoral neck fractures at Vilnius University
      Emergency Hospital during 2004-2006 was carried out. RESULTS: The overall 1- and
      2-year survival rates were 77.4% and 67.1%, respectively. Lower survival rates
      were observed in the internal fixation group than in the primary and secondary
      total hip arthroplasty groups (63.2% vs. 72.0% and 75.1%). Cox proportional
      hazards model analysis showed patient age to be a significant risk factor for
      survival (hazard ratio, 1.05; 95% CI, 1.04-1.07; P<0.001). The overall
      standardized mortality ratio was 2.50. The standardized mortality ratios for men
      and women were 3.07 and 2.27, respectively, but the difference between these
      groups was not significant. CONCLUSIONS: Standardized mortality and survival
      rates decreased with increasing patients' age. Significantly lower survival rates
      were documented in the internal fixation group as compared with primary and
      secondary total hip arthroplasty groups. There was a trend toward a higher
      standardized mortality ratio in men than women, but the difference was not
      significant.

PMID- 22588347
TI  - Correlations between digital planimetry and optical coherence tomography,
      confocal scanning laser ophthalmoscopy in assessment of optic disc parameters.
AB  - OBJECTIVE AND AIM: In routine clinical practice, laser methods for the evaluation
      of optic disc parameters are expensive and not accessible for all
      ophthalmologists; therefore, there is a need for less expensive technique. The
      aim of this study was to assess correlations between the parameters of the optic
      disc measured by digital planimetry (DP), optical coherence tomography (OCT), and
      confocal scanning laser ophthalmoscopy (CSLO) in healthy and glaucoma patients
      with the normal biometric parameters of the eye. MATERIAL AND METHODS: This case
      control study enrolled 40 patients with glaucoma and 32 healthy patients with the
      normal biometric parameters of the eye. All subjects underwent full
      ophthalmologic examination, digital color optic disc photography, OCT, and CSLO
      at the same visit. The optic disc was morphometrically analyzed by DP, OCT, and
      CSLO. Seven optic disc parameters were evaluated. RESULTS: In the glaucoma group,
      the optic disc and cup areas (r=0.7-0.8, P<0.001) and cup-to-optic disc and rim
      to-optic disc area ratios (r=0.7, P<0.001) measured by DP were strongly
      correlated with those measured by OCT and CSLO, while the horizontal and vertical
      cup-to-optic disc diameter ratios were found to be moderately correlated (r=0.6
      0.7, P<0.001). In healthy patients, the optic disc and cup areas were strongly
      correlated (r=0.7-8.0, P<0.001). Significant differences in all optic disc
      parameters, except for the optic disc area, measured by DP, OCT, and CSLO were
      found between glaucoma and healthy patients. CONCLUSIONS: Strong correlations
      between the parameters of the optic disc measured by DP, OCT, and CSLO were
      found. There were significant differences in the parameters between healthy and
      glaucoma eyes measured using DP; therefore, this technique may be used for
      diagnosis, management, and screening of glaucoma.

PMID- 22588348
TI  - Cesarean delivery in severe pulmonary hypertension: a case report.
AB  - Pregnancy in a woman with pulmonary hypertension carries a prohibitively high
      risk of maternal mortality, and pregnancy is contraindicated in such patients.
      Some women decide to continue with their pregnancy despite being aware of
      possible fatal maternal outcome. The management of pulmonary hypertension in
      pregnancy is a challenge and requires a multiprofessional approach. We report the
      case of a patient with severe pulmonary hypertension, who successfully underwent
      elective cesarean section under epidural anesthesia at 38 weeks of gestation and
      discuss major issues associated with the obstetric and anesthetic management of
      pregnant patients with pulmonary hypertension.

PMID- 22588349
TI  - Two unusual clinical presentations of broad-ligament leiomyomas: a report of two
      cases.
AB  - We report on two unusual clinical presentations of broad-ligament leiomyomas. The
      first case was a combination of broad-ligament leiomyoma and ectopic gestational
      sac at the same location. The other case was a broad-ligament leiomyoma
      presenting as an ovarian malignancy. The differential diagnosis of broad-ligament
      leiomyoma should be considered in cases of an adnexal mass. Additionally, a broad
      ligament leiomyoma could be the reason for an ectopic pregnancy.

PMID- 22588350
TI  - The impact of complex cardiac rehabilitation on manifestation of risk factors in
      patients with coronary heart disease.
AB  - BACKGROUND: Each year more than 4.3 million people in Europe will die of
      cardiovascular disease. Therefore, the implementation of simple interventions
      such as smoking cessation, weight loss, improved diets, and increased exercise is
      the top priority in prevention and rehabilitation programs. The aim of this study
      was to evaluate the impact of complex rehabilitation on the manifestation of risk
      factors and cardiac events in patients with coronary heart disease. MATERIAL AND
      METHODS: A total of 140 patients with coronary heart disease and NYHA functional
      class II-IV ischemic heart failure were recruited to the study. The patients were
      divided into 2 groups: 70 patients who underwent a 6-month complex rehabilitation
      course (rehabilitation group) and 70 patients who received drug treatment only
      (control group). Smoking, dietary, and physical activity habits were documented
      using the questionnaires. Blood pressure (BP), body weight and height, and total
      serum cholesterol, low-density lipoprotein (LDL) cholesterol, high-density
      lipoprotein (HDL) cholesterol, triglyceride (Tg), and blood glucose levels were
      measured. Measurements were repeated after 3 and 6 months. RESULTS: After 6
      months, significantly reduced systolic BP was observed in both the groups as
      compared with the baseline values (P<0.05). A significant decrease in the
      diastolic BP; total cholesterol, LDL-cholesterol, triglyceride and blood glucose
      levels; body mass index, and percentage of patients with the metabolic syndrome
      as compared with the baseline data was documented only in the rehabilitation
      group (P<0.05). All the patients quitted smoking as well as all the patients in
      the rehabilitation group changed their dietary habits (P<0.05). Fewer patients
      were excluded from the rehabilitation group because of cardiac events as compared
      with the control group (7.1% vs. 11.4%, P<0.05). CONCLUSIONS: Complex long-term
      rehabilitation of cardiovascular patients significantly reduced the manifestation
      of major cardiovascular risk factors and the rate of cardiac events. Aerobic
      exercise must be the most important part of training but well-done resistance
      training must also be encouraged.

PMID- 22588351
TI  - Early prefrontal functional blockade in rats results in schizophrenia-related
      anomalies in behavior and dopamine.
AB  - Growing evidence suggests schizophrenia may arise from abnormalities in early
      brain development. The prefrontal cortex (PFC) stands out as one of the main
      regions affected in schizophrenia. Latent inhibition, an interesting cognitive
      marker for schizophrenia, has been found in some studies to be reduced in acute
      patients. It is generally widely accepted that there is a dopaminergic
      dysfunctioning in schizophrenia. Moreover, several authors have reported that the
      psychostimulant, D-amphetamine (D-AMP), exacerbates symptoms in patients with
      schizophrenia. We explored in rats the effects in adulthood of neonatal transient
      inactivation of the PFC on behavioral and neurochemical anomalies associated with
      schizophrenia. Following tetrodotoxin (TTX) inactivation of the left PFC at
      postnatal day 8, latent inhibition-related dopaminergic responses and
      dopaminergic reactivity to D-AMP were monitored using in vivo voltammetry in the
      left core part of the nucleus accumbens in adult freely moving rats. Dopaminergic
      responses and behavioral responses were followed in parallel. Prefrontal neonatal
      inactivation resulted in disrupted behavioral responses of latent inhibition and
      latent inhibition-related dopaminergic responses in the core subregion. After D
      AMP challenge, the highest dose (1.5 mg/kg i.p.) induced a greater dopamine
      increase in the core in rats microinjected with TTX, and a parallel increase in
      locomotor activity, suggesting that following prefrontal neonatal TTX
      inactivation animals display a greater behavioral and dopaminergic reactivity to
      D-AMP. Transitory inactivation of the PFC early in the postnatal developmental
      period leads to behavioral and neurochemical changes in adulthood that are
      meaningful for schizophrenia modeling. The data obtained may help our
      understanding of the pathophysiology of this disabling disorder.

PMID- 22588353
TI  - Monitoring the wall mechanics during stent deployment in a vessel.
AB  - Clinical trials have reported different restenosis rates for various stent
      designs. It is speculated that stent-induced strain concentrations on the
      arterial wall lead to tissue injury, which initiates restenosis. This hypothesis
      needs further investigations including better quantifications of non-uniform
      strain distribution on the artery following stent implantation. A non-contact
      surface strain measurement method for the stented artery is presented in this
      work. ARAMIS stereo optical surface strain measurement system uses two optical
      high speed cameras to capture the motion of each reference point, and resolve
      three dimensional strains over the deforming surface. As a mesh stent is deployed
      into a latex vessel with a random contrasting pattern sprayed or drawn on its
      outer surface, the surface strain is recorded at every instant of the
      deformation. The calculated strain distributions can then be used to understand
      the local lesion response, validate the computational models, and formulate
      hypotheses for further in vivo study.

PMID- 22588352
TI  - alpha-1 Adrenergic receptors are localized on presynaptic elements in the nucleus
      accumbens and regulate mesolimbic dopamine transmission.
AB  - Brainstem noradrenergic neurons innervate the mesocorticolimbic reward pathway
      both directly and indirectly, with norepinephrine facilitating dopamine (DA)
      neurotransmission via alpha1-adrenergic receptors (alpha1ARs). Although alpha1AR
      signaling in the prefrontal cortex (PFC) promotes mesolimbic transmission and
      drug-induced behaviors, the potential contribution of alpha1ARs in other parts of
      the pathway, such as the ventral tegmental area (VTA) and nucleus accumbens
      (NAc), has not been investigated before. We found that local blockade of
      alpha1ARs in the medial NAc shell, but not the VTA, attenuates cocaine- and
      morphine-induced locomotion. To determine the neuronal substrates that could
      mediate these effects, we analyzed the cellular, subcellular, and subsynaptic
      localization of alpha1ARs and characterized the chemical phenotypes of alpha1AR
      containing elements within the mesocorticolimbic system using single and double
      immunocytochemical methods at the electron microscopic (EM) level. We found that
      alpha1ARs are found mainly extra-synaptically in axons and axon terminals in the
      NAc and are enriched in glutamatergic and dopaminergic elements. alpha1ARs are
      also abundant in glutamatergic terminals in the PFC, and in GABA-positive
      terminals in the VTA. In line with these observations, microdialysis experiments
      revealed that local blockade of alpha1ARs attenuated the increase in
      extracellular DA in the medial NAc shell following administration of cocaine.
      These data indicate that local alpha1ARs control DA transmission in the medial
      NAc shell and behavioral responses to drugs of abuse.

PMID- 22588354
TI  - Endophthalmitis after intravitreal anti-vascular endothelial growth factor
      antagonists: a six-year experience at a university referral center".

PMID- 22588356
TI  - Lab on a chip: United States of America.

PMID- 22588357
TI  - A practical approach to parameter estimation applied to model predicting heart
      rate regulation.
AB  - Mathematical models have long been used for prediction of dynamics in biological
      systems. Recently, several efforts have been made to render these models patient
      specific. One way to do so is to employ techniques to estimate parameters that
      enable model based prediction of observed quantities. Knowledge of variation in
      parameters within and between groups of subjects have potential to provide
      insight into biological function. Often it is not possible to estimate all
      parameters in a given model, in particular if the model is complex and the data
      is sparse. However, it may be possible to estimate a subset of model parameters
      reducing the complexity of the problem. In this study, we compare three methods
      that allow identification of parameter subsets that can be estimated given a
      model and a set of data. These methods will be used to estimate patient specific
      parameters in a model predicting baroreceptor feedback regulation of heart rate
      during head-up tilt. The three methods include: structured analysis of the
      correlation matrix, analysis via singular value decomposition followed by QR
      factorization, and identification of the subspace closest to the one spanned by
      eigenvectors of the model Hessian. Results showed that all three methods
      facilitate identification of a parameter subset. The "best" subset was obtained
      using the structured correlation method, though this method was also the most
      computationally intensive. Subsets obtained using the other two methods were
      easier to compute, but analysis revealed that the final subsets contained
      correlated parameters. In conclusion, to avoid lengthy computations, these three
      methods may be combined for efficient identification of parameter subsets.

PMID- 22588358
TI  - Propagation of CaMKII translocation waves in heterogeneous spiny dendrites.
AB  - CaMKII (Ca2+-calmodulin-dependent protein kinase II) is a key regulator of
      glutamatergic synapses and plays an essential role in many forms of synaptic
      plasticity. It has recently been observed experimentally that stimulating a local
      region of dendrite not only induces the local translocation of CaMKII from the
      dendritic shaft to synaptic targets within spines, but also initiates a wave of
      CaMKII translocation that spreads distally through the dendrite with an average
      speed of order 1 MUm/s. We have previously developed a simple reaction-diffusion
      model of CaMKII translocation waves that can account for the observed wavespeed
      and predicts wave propagation failure if the density of spines is too high. A
      major simplification of our previous model was to treat the distribution of
      spines as spatially uniform. However, there are at least two sources of
      heterogeneity in the spine distribution that occur on two different spatial
      scales. First, spines are discrete entities that are joined to a dendritic branch
      via a thin spine neck of submicron radius, resulting in spatial variations in
      spine density at the micron level. The second source of heterogeneity occurs on a
      much longer length scale and reflects the experimental observation that there is
      a slow proximal to distal variation in the density of spines. In this paper, we
      analyze how both sources of heterogeneity modulate the speed of CaMKII
      translocation waves along a spiny dendrite. We adapt methods from the study of
      the spread of biological invasions in heterogeneous environments, including
      homogenization theory of pulsating fronts and Hamilton-Jacobi dynamics of sharp
      interfaces.

PMID- 22588359
TI  - A systematic review of parenting interventions for traumatic brain injury: child
      and parent outcomes.
AB  - OBJECTIVE: To evaluate the efficacy of parenting interventions on child and
      parent behavioral and emotional outcomes for parents of children with traumatic
      brain injury (TBI). METHODS: Systematic searches of 5 databases. Included studies
      were assessed for quality, and relevant data were extracted and collated.
      RESULTS: Eight articles met inclusion criteria, reporting 6 trials of
      interventions involving parent training for parents of children with TBI. Only 1
      pre-post study trialed a version of a traditional parenting intervention. The
      remaining studies involved a multicomponent family problem-solving intervention.
      Each trial found a statistically significant intervention effect for at least 1
      outcome measure. CONCLUSIONS: Interventions that train parents may be a useful
      approach to alleviate behavioral and emotional disturbances after pediatric TBI.
      Some evidence suggests that these interventions may help to improve parenting
      skill and adjustment. However, all identified studies included interventions with
      multiple treatment components, so the effects attributable to parent training
      alone remain undetermined. Further quality trials are needed to assess the unique
      effectiveness of parenting interventions in this population.

PMID- 22588360
TI  - Time course of clinical and electrophysiological recovery after sport-related
      concussion.
AB  - BACKGROUND AND PURPOSE: Recent neuroimaging studies suggest that abnormalities in
      brain function after concussion exist beyond the point of observed clinical
      recovery. This study investigated the relationship between an index of brain
      dysfunction (traumatic brain injury [TBI] Index), concussion severity, and
      outcome. METHODS: EEG was collected from forehead locations in 65 male athletes
      with concussion within 24 hours of concussion, with follow-up at 8 and 45 days
      postinjury. Neurocognitive and symptom assessments were also performed and used
      to classify subjects in mild or moderate concussion categories. Time to return to
      play was recorded. RESULTS: The TBI Index was higher in the moderate than mild
      concussion group at injury, day 8, and day 45. The moderate group had increased
      symptoms and decreased cognitive performance only at the time of injury. At the
      time of injury, only the TBI Index was significantly associated with the length
      of time to return to play. CONCLUSIONS: Recovery of brain function after sport
      related concussion may extend well beyond the time course of clinical recovery
      and be related to clinical severity. An index of brain dysfunction may be an
      objective indicator of injury, recovery, and readiness to return to play. The
      relatively small sample indicates the need for further study on the time course
      of physiological recovery.

PMID- 22588361
TI  - Effect of dehydroepiandrosterone administration on recovery from mix-type
      exercise training-induced muscle damage.
AB  - This study aimed to determine the role of DHEA-S in coping against the exercise
      training mixing aerobic and resistance components. During 5-day successive
      exercise training, 16 young male participants (19.2 +/- 1.2 years) received
      either a placebo (flour capsule) or DHEA (100 mg/day) in a double-blinded and
      placebo-controlled design. Oral DHEA supplementation significantly increased
      circulating DHEA-S by 2.5-fold, but a protracted drop (~35 %) was observed from
      Day 3 during training. In the Placebo group, only a minimal DHEA-S reduction (~17
      %) was observed. Changes in testosterone followed a similar pattern as DHEA-S.
      Muscle soreness was elevated significantly on Day 2 for both groups to a similar
      extent. Lower muscle soreness was observed in the DHEA-supplemented group on Day
      3 and Day 6. In the Placebo group, training increased circulating creatine kinase
      (CK) levels by approximately ninefold, while only a threefold increase was
      observed in the DHEA-supplemented group. This mix-type exercise training improved
      glucose tolerance in both groups, while lowering the insulin response to the
      glucose challenge, but no difference between treatments was observed. Our results
      suggest that DHEA-S may play a role in protecting skeletal muscle from exercise
      training-induced muscle damage.

PMID- 22588362
TI  - Doll play narratives about starting school in children of socially anxious
      mothers, and their relation to subsequent child school-based anxiety.
AB  - Child social anxiety is common, and predicts later emotional and academic
      impairment. Offspring of socially anxious mothers are at increased risk. It is
      important to establish whether individual vulnerability to disorder can be
      identified in young children. The responses of 4.5 year-old children of mothers
      with social phobia (N = 62) and non-anxious mothers (N = 60) were compared, two
      months before school entry, using a Doll Play (DP) procedure focused on the
      social challenge of starting school. DP responses were examined in relation to
      teacher reports of anxious-depressed symptoms and social worries at the end of
      the child's first school term. The role of earlier child behavioral inhibition
      and attachment, assessed at 14 months, was also considered. Compared to children
      of non-anxious mothers, children of mothers with social phobia were significantly
      more likely to give anxiously negative responses in their school DP (OR = 2.57).
      In turn, negative DP predicted teacher reported anxious-depressed and social
      worry problems. There were no effects of infant behavioral inhibition or
      attachment. Vulnerability in young children at risk of anxiety can be identified
      using Doll Play narratives.

PMID- 22588363
TI  - Calcium and vitamin D in obesity.
AB  - New and more effective nutritional measures are urgently needed for the
      prevention of obesity. The role of Ca and vitamin D in obesity has been recently
      implicated. Low Ca intake and low vitamin D status have been linked with an
      increased risk of obesity in epidemiological studies; however, clinical
      intervention trials designed to test this association have produced controversial
      results. The suggested anti-obesity mechanisms of Ca and vitamin D include the
      regulation of adipocyte death (apoptosis), adipogenesis and lipid metabolism.
      Dietary Ca has been also shown to increase faecal fat excretion. The potential
      role of Ca and vitamin D in shifting energy balance towards a more negative state
      is an area of considerable interest. Ultimately, a review of recent research
      findings does not allow the reaching of a definitive conclusion that increasing
      Ca intake and rising vitamin D status will influence fat mass and body weight or
      decrease the risk of obesity and overweight.

PMID- 22588364
TI  - [Hypertension and nutrition. Position paper of the Austrian Nutrition Society].
AB  - Arterial hypertension is one of the leading causes of overall mortality and is
      responsible for a high proportion of deaths due to stroke as well as coronary
      heart disease. It is defined as a pathological elevation of blood pressure which
      leads to damage of the cardiovascular system. Cut-off values for hypertension are
      defined as blood pressure levels higher than 140/90 mmHg (systolic/diastolic). In
      the pathogenesis of hypertension genetic factors, age and sex play a role, as
      well as body weight and lifestyle factors, such as nutrition and physical
      exercise. Lifestyle optimization reduces the risk of developing hypertension and
      contributes to the treatment in patients with established hypertension.
      Nutritional factors associated with hypertension are discussed in this article
      and recommendations regarding diet are made based on the literature. The
      nutritional factors with the highest impact on blood pressure are reduction of
      salt intake, a diet rich in potassium, weight management, the DASH (dietary
      approach to stop hypertension) diet and moderation of alcohol consumption. Salt
      restriction is essential in the prevention and treatment of hypertension. Based
      on the literature, in this article recommendations for nutrition and hypertension
      are given.

PMID- 22588365
TI  - High exposure rates of anticoagulant rodenticides in predatory bird species in
      intensively managed landscapes in Denmark.
AB  - The extensive use of anticoagulant rodenticides (ARs) for rodent control has led
      to widespread secondary exposure in nontarget predatory wildlife species. We
      investigated exposure rates and concentrations of five ARs in liver samples from
      five raptors and six owls from Denmark. A total of 430 birds were analysed. ARs
      were detected in 84-100 % of individual birds within each species. Multiple AR
      exposure was detected in 73 % of all birds. Average number of substances detected
      in individual birds was 2.2 with no differences between owls and raptors.
      Difenacoum, bromadiolone, and brodifacoum were the most prevalent substances and
      occurred in the highest concentrations. Second-generation ARs made up 96 % of the
      summed AR burden. Among the six core species (sample size >30), summed AR
      concentrations were lower in rough-legged buzzard (Buteo lagopus) and long-eared
      owl (Asio otus) than in barn owl (Tyto alba), buzzard (B. buteo), kestrel (Falco
      tinnunculus), and tawny owl (Strix aluco). There was a strong tendency for
      seasonal variations in the summed AR concentration with levels being lowest
      during autumn, which is probably related to an influx of less-exposed migrating
      birds from northern Scandinavia during autumn. High hepatic AR residue
      concentrations (>100 ng/g wet weight), which have been associated with symptoms
      of rodenticide poisoning and increased mortality, were recorded high frequencies
      (12.9-37.4 %) in five of the six core species. The results suggest that the
      present use of ARs in Denmark, at least locally, may have adverse effects on
      reproduction and, ultimately, population status in some raptors and owls.

PMID- 22588366
TI  - Axis of ageing: telomeres, p53 and mitochondria.
AB  - Progressive DNA damage and mitochondrial decline are both considered to be prime
      instigators of natural ageing. Traditionally, these two pathways have been viewed
      largely in isolation. However, recent studies have revealed a molecular circuit
      that directly links DNA damage to compromised mitochondrial biogenesis and
      function via p53. This axis of ageing may account for both organ decline and
      disease development associated with advanced age and could illuminate a path for
      the development of relevant therapeutics.

PMID- 22588368
TI  - Genetic reassortment between Sathuperi and Shamonda viruses of the genus
      Orthobunyavirus in nature: implications for their genetic relationship to
      Schmallenberg virus.
AB  - The recent outbreak of malformations in ruminants in Northern Europe caused by
      Schmallenberg virus induced us to analyze the genetic properties of the related
      orthobunyaviruses and clarify their relationship. The sequencing of three genomic
      RNA segments of Sathuperi, Shamonda and Douglas viruses (SATV, SHAV and DOUV)
      revealed that the M RNA segment of SATV and DOUV had a high degree of sequence
      identity with that of Schmallenberg virus, but the S and L RNA segments closely
      matched those of SHAV. Phylogenetic analysis of the three genomic RNA segments
      indicated that Schmallenberg virus is a reassortant, with the M RNA segment from
      SATV and the S and L RNA segments from SHAV.

PMID- 22588367
TI  - Geometry and force behind kinetochore orientation: lessons from meiosis.
AB  - During mitosis, replicated chromosomes (sister chromatids) become attached at the
      kinetochore by spindle microtubules emanating from opposite poles and segregate
      equationally. In the first division of meiosis, however, sister chromatids become
      attached from the same pole and co-segregate, whereas homologous chromosomes
      connected by chiasmata segregate to opposite poles. Disorder in this specialized
      chromosome attachment in meiosis is the leading cause of miscarriage in humans.
      Recent studies have elucidated the molecular mechanisms determining chromosome
      orientation, and consequently segregation, in meiosis. Comparative studies of
      meiosis and mitosis have led to the general principle that kinetochore geometry
      and tension exerted by microtubules synergistically generate chromosome
      orientation.

PMID- 22588369
TI  - DNA binding, nuclease activity and cytotoxicity studies of Cu(II) complexes of
      tridentate ligands.
AB  - Cu(II) complexes of three tridentate ligands, L(1), L(2) and L(3), [L(1), N-((1H
      imidazole-2-yl)methyl)-2-(pyridine-2-yl)ethanamine; L(2), N-((1-methyl-1H
      imidazole-2-yl)methyl)-2-(pyridine-2-yl)ethanamine; L(3), 2-(pyridine-2-yl)-N
      ((pyridine-2-yl)methyl)ethanamine] respectively, were synthesized and
      characterized. The single crystal X-ray structure of complex 1 reveals the pseudo
      octahedral coordination geometry around the copper center. Absorption and
      fluorescence experimental evidence show good DNA binding propensity (in the order
      of 10(5) M(-1)) of the complexes. Thermal denaturation and circular dichroism
      (CD) analyses reveal minor structural changes of calf thymus (CT) DNA in presence
      of complexes and groove and/or surface binding of the complexes to CT-DNA.
      Kinetic DNA cleavage assay shows pseudo-first-order kinetic reaction between the
      complex and supercoiled (SC) DNA. In addition, mechanistic SC DNA cleavage
      results show higher DNA cleavage activity in presence of reducing agent, due to
      the presence of hydroxyl radicals. In vitro cytotoxicity assay of the complexes
      demonstrate that the complexes have low toxicity for different cancer cell lines
      and IC(50) values were between 37 and 156 MUM.

PMID- 22588370
TI  - Wernicke's encephalopathy and Korsakoff's syndrome revisited.

PMID- 22588371
TI  - A novel mixed-component molecular hydrogel system with excellent stabilities.
AB  - We report a novel mixed-component molecular hydrogel system with excellent
      stabilities against dilution and enzyme digestion.

PMID- 22588372
TI  - Vortical flow in the utricle and the ampulla: a computational study on the fluid
      dynamics of the vestibular system.
AB  - We present a computational study of the fluid dynamics in healthy semicircular
      canals (SCCs) and the utricle. The SCCs are the primary sensors for angular
      velocity and are located in the vestibular part of the inner ear. The SCCs are
      connected to the utricle that hosts the utricular macula, a sensor for linear
      acceleration. The transduction of angular motion is triggered by the motion of a
      fluid called endolymph and by the interaction of this fluid with the sensory
      structures of the SCC. In our computations, we observe a vortical flow in the
      utricle and in the ampulla (the enlarged terminal part of the SCCs) which can
      lead to flow velocities in the utricle that are even higher than those in the
      SCCs. This is a fundamentally new result which is in contrast to the common
      belief that the fluid velocities in the utricle are negligible from a
      physiological point of view. Moreover, we show that the wall shear stresses in
      the utricle and the ampulla are maximized at the positions of the sensory
      epithelia. Possible physiological and clinical implications are discussed.

PMID- 22588373
TI  - Hemodynamic consequences of auto-PEEP.
AB  - Auto-positive end-expiratory pressure (PEEP) is a common but frequently
      unrecognized problem in critically ill patients. It has important physiologic
      consequences and can cause shock and cardiac arrest. Treatment consists of
      relieving expiratory airflow obstruction and reducing minute ventilation
      delivered by positive pressure ventilation. Sedation and fluid management are
      important adjunctive therapies. This analytic review discusses the prevalence,
      pathophysiology, and hemodynamic consequences of auto-PEEP and an approach to its
      treatment. 

PMID- 22588374
TI  - Reality bites: a case of severe rattlesnake envenomation.
AB  - Rattlesnake venoms can cause a wide range of adverse human health effects.
      However, with the availability of modern antivenin, toxicity can generally be
      minimized and controlled. We present a rare case of rattlesnake envenomation
      resulting in severe systemic effects and syndrome relapse. Management
      considerations and patient course are described in the context of the current
      literature. 

PMID- 22588375
TI  - Respiratory perioperative management of patients with obstructive sleep apnea.
AB  - Obstructive sleep apnea (OSA) has become a major public health problem in the
      United State and Europe. However, perioperative strategies regarding diagnostic
      options and management of untreated OSA remain inadequate. Preoperative screening
      and identification of patients with undiagnosed OSA may lead to early
      perioperative interventions that may alter cardiopulmonary events associated with
      surgery and anesthesia.(1) Hence, clinicians need to become familiar with the
      preoperative screening and diagnosis of OSA. Perioperative management of a
      patient with OSA should be modified and may include regional anesthesia and
      alternative analgesic techniques such as nonsteroidal anti-inflammatory drugs
      that may reduce the need for systemic opioids. Additionally, supplemental oxygen
      and continuous pulse oximetry monitoring should be utilized to maintain baseline
      oxygen saturation. Postoperatively patients should remain in a semi-upright
      position and positive pressure therapy should be used in patients with high-risk
      OSA. 

PMID- 22588377
TI  - The Coping Cat program for children with anxiety and autism spectrum disorder: a
      pilot randomized controlled trial.
AB  - The purpose of this pilot study was to evaluate whether a modified version of the
      Coping Cat program could be effective in reducing anxiety in children with autism
      spectrum disorder (ASD). Twenty-two children (ages 8-14; IQ >= 70) with ASD and
      clinically significant anxiety were randomly assigned to 16 sessions of the
      Coping Cat program (cognitive-behavioral therapy; CBT) or a 16-week waitlist.
      Children in the CBT condition evidenced significantly larger reductions in
      anxiety than those in the waitlist. Treatment gains were largely maintained at
      two-month follow-up. Results provide preliminary evidence that a modified version
      of the Coping Cat program may be a feasible and effective program for reducing
      clinically significant levels of anxiety in children with high-functioning ASD.

PMID- 22588378
TI  - An injectable nucleus pulposus implant restores compressive range of motion in
      the ovine disc.
AB  - STUDY DESIGN: Investigation of injectable nucleus pulposus (NP) implant.
      OBJECTIVE: To assess the ability of a recently developed injectable hydrogel
      implant to restore nondegenerative disc mechanics through support of NP
      functional mechanics. SUMMARY OF BACKGROUND DATA: Although surgical intervention
      for low back pain is effective for some patients, treated discs undergo altered
      biomechanics and adjacent levels are at increased risk for accelerated
      degeneration. One potential treatment as an alternative to surgery for
      degenerated disc includes the percutaneous delivery of agents to support NP
      functional mechanics. The implants are delivered in a minimally invasive fashion,
      potentially on an outpatient basis, and do not preclude later surgical options.
      One of the challenges in designing such implants includes the need to match key
      NP mechanical behavior and mimic the role of native nondegenerate NP in spinal
      motion. METHODS: The oxidized hyaluronic acid gelatin implant material was
      prepared. In vitro mechanical testing was performed in mature ovine bone-disc
      bone units in 3 stages: intact, discectomy, and implantation versus sham. Tested
      samples were cut axially for qualitative structural observations. RESULTS:
      Discectomy increased axial range of motion (ROM) significantly compared with
      intact. Hydrogel implantation reduced ROM 17% (P < 0.05) compared with discectomy
      and returned ROM to intact levels (ROM intact 0.71 mm, discectomy 0.87 mm,
      postimplantation 0.72 mm). Although ROM for the hydrogel implant group was
      statistically unchanged compared with the intact disc, ROM for sham discs, which
      received a discectomy and no implant, was significantly increased compared with
      intact. The compression and tension stiffness were decreased with discectomy and
      remained unchanged for both implant and sham groups as expected because the
      annulus fibrosus was not repaired. Gross morphology images confirmed no ejection
      of NP implant. CONCLUSION: An injectable implant that mimics nondegenerate NP has
      the potential to return motion segment ROM to normal subsequent to injury.

PMID- 22588379
TI  - The prevalence and risk factors of low back pain in rural community residents of
      Korea.
AB  - STUDY DESIGN: A community-based, cross-sectional study that is part of the
      prospective Korean Health and Genome Study. OBJECTIVE: To determine the
      prevalence of low back pain (LBP) among middle-aged and elderly rural community
      residents in Korea and to examine the relevant risk factors, including activities
      reflecting the Asian lifestyle, and the relationship between radiographical
      features of degenerative changes in the lumbar spine and LBP. SUMMARY OF
      BACKGROUND DATA: The prevalence and implication of LBP among the elderly,
      particularly Asians, are under-represented in previous reports. METHODS: Data for
      LBP were collected for 4181 subjects from a rural farming community. The point
      and cumulative lifetime prevalences of LBP were obtained in addition to
      measurement of the severity of LBP. Lateral lumbar spine radiographs were
      obtained according to a standard protocol. RESULTS: The mean age of the study
      subjects was 56 years and 55% were women. The lifetime prevalence of LBP was
      61.3%, with women having a higher prevalence. The point and 6-month prevalences
      were also higher among women. The lifetime, point, and 6-month prevalences
      increased with age in both sexes, except for lifetime prevalence in men. The
      prevalence of LBP of grade 3 or more was significantly higher in women and
      increased significantly with age, particularly in women. Both lifetime and point
      of prevalence of LBP were significantly associated with age, female sex, and time
      spent squatting. After adjusting for age and sex, the presence of disc space
      narrowing, osteophytes, and advanced Kellgren-Lawrence grade in lumbar radiograph
      was associated with LBP. CONCLUSION: The prevalence of LBP is comparable between
      these Korean community residents and other population groups. Risk factors
      associated with LBP included advanced age, female sex, squatting, the presence of
      osteophytes, joint space narrowing, and advanced Kellgren-Lawrence grading on
      lumbar radiograph.

PMID- 22588380
TI  - Difficulty of diagnosing the origin of lower leg pain in patients with both
      lumbar spinal stenosis and hip joint osteoarthritis.
AB  - STUDY DESIGN: Case series. OBJECTIVE: To present the difficulty of diagnosing the
      origin of lower leg pain in patients with lumbar spinal stenosis and hip joint
      arthritis. SUMMARY OF BACKGROUND DATA: Pain arising from a degenerated hip joint
      is sometimes localized to the lower leg. Patients with lumbar spinal disease may
      also show radicular pain corresponding to the lower leg area. If patients present
      with both conditions and only pain at the lower leg, it is difficult to determine
      the origin of the pain. METHODS: We reviewed 420 patients who had leg pain with
      lumbar spinal stenosis diagnosed by myelography, computed tomography after
      myelography, or magnetic resonance imaging. Pain only at the ipsilateral lateral
      aspect of the lower leg but slight low back pain or pain around the hip joint was
      shown in 4 patients who had lumbar spinal stenosis and hip osteoarthritis. The
      symptoms resolved after L5 spinal nerve block, but remained after lidocaine
      infiltration into the hip joint. We performed decompression and posterolateral
      fusion surgery for these 4 patients. RESULTS: Leg pain did not resolve after
      lumbar surgery in all patients. Conservative treatment was not effective from 6
      to 12 months, so ultimately we performed ipsilateral total hip replacement for
      all patients and they became symptom-free. CONCLUSION: It is difficult to
      determine the origin of lower leg pain by spinal nerve block and hip joint block
      in patients with lumbar spinal stenosis and hip osteoarthritis. We take this into
      consideration before surgery.

PMID- 22588381
TI  - Does the formation of vertebral endplate cysts predict nonunion after lumbar
      interbody fusion?
AB  - STUDY DESIGN: A retrospective study was conducted to investigate the impact of
      vertebral endplate cyst formation on union status after lumbar interbody fusion.
      OBJECTIVE: To assess the impact of cyst formation at the vertebral endplate in
      the early detection of nonunion after lumbar interbody fusion. The relationship
      between vertebral endplate cyst formation and subsequent union status was
      evaluated retrospectively using dynamic x-ray and computed tomography (CT) and
      multiplanar reconstruction. SUMMARY OF BACKGROUND DATA: Although many studies
      have reported on the assessment of bony union after lumbar interbody fusion, no
      study has reported on the radiological risk factors for nonunion in the early
      postoperative period. The meaning and importance of vertebral endplate cyst
      formation have not been reported and should be clarified. METHODS: Radiological
      vertebral endplate changes at 93 levels were assessed in 76 patients after
      transforaminal lumbar interbody fusion, using a titanium cage with pedicle screw
      fixation. Computed tomographic findings for the vertebral endplate at 3 months
      were compared between nonunion and union cases. The relationship between
      vertebral endplate cyst formation and union status was tested statistically.
      RESULTS: Fifty-nine union cases were compared with 17 nonunion cases. The overall
      union rate was 75.2% at 1 year and 82.8% at 2 years. At 1 year, the sensitivity
      of cyst formation for subsequent nonunion was 69.6%, specificity was 100%,
      positive predictive value was 100%, and negative predictive value was 90.9%.
      Multivariate logistic regression analysis showed that a multioperated back was a
      significant predictor of cyst formation (odds ratio [OR]: 3.8; 95% confidence
      interval [CI]: 1.1-13.1) and that cyst formation and multioperated back were
      significant predictors of nonunion (OR: 12.3; 95% CI: 1.8-133 and OR: 116; 95%
      CI: 22.4-infinity, respectively). CONCLUSION: These findings show a relationship
      between vertebral endplate cyst formation in the early postoperative period and
      nonunion after lumbar interbody fusion. Endplate cyst formation is a useful early
      predictor of subsequent nonunion.

PMID- 22588382
TI  - Primary extensive spinal subarachnoid cysticercosis.
AB  - STUDY DESIGN: A case report. OBJECTIVE: To describe a patient with a primary
      extensive spinal subarachnoid cysticercosis that was successfully treated with a
      combination of surgical removal and albendazole. SUMMARY OF BACKGROUND DATA:
      Neurocysticercosis (NCC) is the most common parasitic infection of the central
      nervous system. It is mostly intracranial, but primary cysticercosis, although
      rare, can occur in the spinal canal. Neurological morbidity can occur if NCC is
      not properly treated; therefore, NCC should be considered as a lesion of primary
      nerve compression, which occurs within spinal canal as well as cranial cavity.
      METHODS: A 48-year-old male patient presented with an 18-month history of
      progressive lower limb weakness and urinary incontinence. Contrast-enhanced
      lumbar magnetic resonance image showed multiple intradural and extramedullary
      masses and cysts from T12 to S1. A cervicothoracic magnetic resonance image
      revealed whole cervical and upper thoracic involvement. The patient was treated
      with a combination of surgical removal and orally administered albendazole.
      RESULTS: A histopathological examination confirmed cysticercosis. After the
      treatment, cysticercosis had disappeared on follow-up. The patient's motor
      weakness in the lower limbs and urinary function were improved. CONCLUSION:
      Spinal subarachnoid cysticercosis can occur via direct hematogenous dissemination
      from a gastrointestinal tract. The primary spinal cysticercosis can be dropped
      distantly in the spinal cavity by cerebrospinal fluid circulation like
      intracranial cysticercosis, and extensive spinal subarachnoid cysticercosis can
      be successfully treated with a combination of surgical removal and cysticidal
      drugs.

PMID- 22588383
TI  - Scoliosis associated with airflow obstruction due to endothoracic vertebral hump.
AB  - STUDY DESIGN: A retrospective clinical study of scoliosis-associated airflow
      obstruction due to endothoracic vertebral hump. OBJECTIVE: The purpose of this
      study was to evaluate and present anatomical features of patients with scoliosis
      who showed airflow obstruction caused by endothoracic vertebral hump. SUMMARY OF
      BACKGROUND DATA: It is well known that severe scoliosis causes airflow
      restriction due to thoracic cage deformity. There have been few reports of
      clinical data and anatomical features on scoliosis associated with airflow
      obstruction due to endothoracic vertebral hump. METHODS: The subjects were 6
      patients. The diagnoses were idiopathic scoliosis in 3 patients, symptomatic
      scoliosis in 2 patients, and thoracogenic scoliosis in 1 patient. The
      radiological outcome, comorbidities, pre- and postoperative respiratory function,
      and surgical complication were analyzed. RESULTS: Four patients had preoperative
      atelectasis on the convex side of the lower lobe and improved after the
      operations. All patients showed main thoracic curves and their apex was located
      at T7-T9. All patients had lordoscoliosis except 1, who demonstrated kyphosing
      scoliosis. The correction rate was 78% (62.8%-83.5%). Preoperative thoracic
      lordosis within the range of -5 degrees  to -47 degrees  was postoperatively
      corrected to a substantially normal kyphosis within the range of 9 degrees  to 24
      degrees . The average vital capacity, percent VC improved from 0.72 L (0.33-1.17
      L) to 1.21 L (0.82-1.71 L) and 45.5% (37.3%- 50.8%) to 63.7% (41.0%-88.6%)
      relatively. Spine Penetration Index improved from 23% (18%-35%) to 16% (13%-19%).
      Endothoracic hump ratio improved from 1.34 (0.98-1.93) to 1.12 (0.86-1.28).
      CONCLUSION: Each patient with symptomatic scoliosis and thoracogenic scoliosis
      required relatively long periods of respiration management. Patients having
      lordoscoliosis with an apex located between T7 and T9 may develop airflow
      obstruction due to an endothoracic vertebral hump. Correction of lordoscoliosis
      through anterior and posterior approaches successfully improved endothoracic hump
      ratio and atelectasis in all patients.

PMID- 22588384
TI  - Increased expression of netrin-1 and its deleted in colorectal cancer receptor in
      human diseased lumbar intervertebral disc compared with autopsy control.
AB  - STUDY DESIGN: The expression of netrin-1 and its deleted in colorectal cancer
      (DCC) receptor was investigated in human lumbar discs using immunohistochemistry.
      OBJECTIVE: To investigate the expression of netrin-1 and DCC receptor in human
      diseased and healthy lumbar intervertebral discs (IVDs) and to clarify the
      correlation between netrin-1 expression and the degree of neurovascular ingrowth.
      SUMMARY OF BACKGROUND DATA: Previous studies have shown neurovascular ingrowth
      into the inner regions of degenerated IVD and suggested that the ingrowth may
      contribute to discogenic low back pain. Netrin-1 is an axon guidance molecule
      that regulates axons seeking their final targets and has been identified as
      involved in various pathological conditions, so is its DCC receptor. However, the
      role of netrin-1 in diseased IVDs remains unknown. METHODS: Thirty-five diseased
      IVD specimens were collected from 34 patients with different lumbar diseases
      during posterior lumbar interbody fusion. Eight normal discs were obtained at
      autopsy as control. Using polyclonal or monoclonal antibody, the disc slides were
      immmunostained to detect the expression and distribution of netrin-1, the DCC,
      the neuronal marker (neurofilament), and the vascular endothelial cell marker
      (CD34). RESULTS: Netrin-1 and DCC immunopositive cells distributed substantially
      from the annulus fibrosus to the nucleus pulposus (NP), and the immunopositivity
      was detected in the disc cells, endothelial cells and granulation tissue cells in
      the diseased discs. The percentage of netrin-1 positive disc cells of the NP was
      more than that of the annulus fibrosus. The expression of netrin-1 and DCC was
      weak in the normal discs. A significant positive correlation between the
      percentage of netrin-1 immunopositive disc cells and neurovascular scores was
      found. CONCLUSION: The increased expression of netrin-1 and DCC in diseased IVDs
      compared with controls suggested that they might play an important role in the
      process of neurovascular ingrowth.

PMID- 22588385
TI  - Diphenylarsinic acid increased the synthesis and release of neuroactive and
      vasoactive peptides in rat cerebellar astrocytes.
AB  - An incident of poisoning occurred in Japan in 2003 when high-level contamination
      with arsenic, mainly diphenylarsinic acid (DPAA), was found in well water. People
      using this water particularly experienced cerebellar symptoms. In the present
      study, we investigated the adverse effects of DPAA on the cerebellum in vitro and
      in vivo to understand the biological mechanisms that cause cerebellar symptoms.
      Comprehensive gene expression analyses in primary cultured ratcerebellar cells
      exposed to 10 MUM DPAA for 24 hours indicated significant alterations in the mRNA
      expression of genes encoding antioxidative stress proteins (heme oxigenase 1 and
      heat shock protein72) and neuroactive and vasoactive peptides (neuropeptide Y,
      adrenomedullin, monocyte chemoattractant protein 1, and fibroblast growth factor
      2). Further analyses of proteins revealed that cultured cerebellar astrocytes
      expressed these antioxidative stress proteins and peptides in response to
      exposure to DPAA. In addition, these adverseeffects were also observed in the
      cerebellum exposed in vivo to DPAA (100 mg/L) for 21 days. These results
      suggested that cerebellarastrocytes irregularly secrete neuroactive and
      vasoactive peptidesagainst DPAA-induced oxidative stress, which leads to abnormal
      neural functions and disrupted cerebellar autoregulation dynamics and results in
      the onset of cerebellar symptoms.

PMID- 22588386
TI  - SC1/hevin identifies early white matter injury after ischemia and intracerebral
      hemorrhage in young and aged rats.
AB  - The progression of white matter damage after ischemic and hemorrhagic strokes can
      exacerbate the initial injury, but little is known about the processes involved.
      We show that the antiadhesive matricellular glycoprotein SC1 is a novel early
      marker of white matter damage in 3 models of acute injury in the rat striatum:
      transient focal ischemia, intracerebral hemorrhage, and a needle penetration
      wound. SC1 was restricted to the damaged portions of axon bundles that bordered
      stroke lesions in young-adult and aged rats. SC1 peaked at 1 and 3 days after
      intracerebral hemorrhage and at 7 days after ischemia. The SC1-positive bundles
      usually expressed degraded myelin basic protein and amyloid precursor protein, a
      marker of axonal injury. At the hematoma edge, SC1 was seen in a few axon bundles
      that retained myelin basic protein staining. In these bundles, punctate SC1
      staining filled individual axons, extended beyond a core of pan-axonal
      neurofilament and NF200 and was inside or overlapped with myelin basic protein
      staining when it was present. Aged rats had less SC1 (and amyloid precursor
      protein) after both types of stroke, suggesting a reduced axonal response. SC1
      also labeled amyloid precursor protein-positive axon bundles along the needle
      penetration tract of saline-injected rats; thus, SC1 appears to characterize
      damaged striatal white matter damage after multiple types of injury.

PMID- 22588387
TI  - Proliferating immature Schwann cells contribute to nerve regeneration after
      ischemic peripheral nerve injury.
AB  - Schwann cells exhibit a high degree of plasticity in adult peripheral nerves
      after mechanical injury; they have, therefore, been implicated in promoting nerve
      regeneration. However, Schwann cell behavior after ischemic injury has not yet
      been elucidated. To determine how Schwann cell plasticity may contribute to
      recovery from ischemic neuropathy, we used a rat model in which ischemia was
      induced in the tibial nerve by a 5-hour occlusion of the supplying arteries.
      Proliferation of immature Schwann cells that emerged in the injured nerve was
      evaluated by double immunostaining for the p75 neurotrophin receptor and
      proliferating cell nuclear antigen. The number of proliferating cell nuclear
      antigen/p75 neurotrophin receptor double-positive cells increased significantly
      in 1 to 2 weeks after ischemia and subsequently decreased by 4 weeks. During this
      time, the postmitotic Schwann cells differentiated into mature cells, as
      demonstrated with bromodeoxyuridine incorporation, which facilitated axon
      guidance and subsequent axon remyelination. These results suggest the emergence
      and proliferation of immature Schwann cells that contribute to nerve regeneration
      after ischemic injury. The manipulation of this population of proliferating
      immature Schwann cells may be a useful strategy for treating ischemic peripheral
      neuropathy.

PMID- 22588388
TI  - Glucagon-like peptide 1, insulin, sensory neurons, and diabetic neuropathy.
AB  - Like insulin, glucagon-like peptide 1 (GLP-1) may have direct trophic actions on
      the nervous system, but its potential role in supporting diabetic sensory neurons
      is uncertain. We identified wide expression of GLP-1 receptors on dorsal root
      ganglia sensory neurons of diabetic and nondiabetic mice. Exendin-4, a GLP-1
      agonist, increased neurite outgrowth of adult sensory neurons in vitro. To
      determine the effects ofexendin-4 in comparison with continuous low- or high-dose
      insulin in vivo, we evaluated parallel cohorts of type 1 (streptozotocin-induced)
      and type 2 (db/db) mice of 2 months' diabetes duration with established
      neuropathy during an additional month of treatment. High-dose insulin alone
      reversed hyperglycemia in type 1 diabetic mice, partly reversed thermal sensory
      loss, improved epidermal innervation but failed to reverse electrophysiological
      abnormalities. Exendin-4 improved both sensory electrophysiology and behavioral
      sensory loss. Low-dose insulin was ineffective. In type 2 diabetes, hyperglycemia
      was uncorrected, and neither insulin nor exendin-4 reversed sensory
      electrophysiology, sensory behavior, or loss of epidermal axons. However, exendin
      4 alone improved motor electrophysiology. Receptor for advanced glycosylated end
      products and nuclear factor-kappaB neuronal expression were not significantly
      altered by diabetes or treatment. Taken together, these results suggest that
      although GLP-1 agonists and insulin alone are insufficient to reverse all
      features of diabetic neuropathy, in combination, they might benefit some aspects
      of established diabetic neuropathy.

PMID- 22588390
TI  - Radiologic case study.

PMID- 22588392
TI  - Evaluation and treatment of painful total hip arthroplasties with modular metal
      taper junctions.
AB  - Modern primary total hip arthroplasty femoral components have evolved to include
      modular necks. Subsequently, the additional taper junction provides another
      interface as a potential source for mechanically assisted crevice corrosion,
      which is a complex process involving fretting and crevice corrosion. Furthermore,
      it is becoming evident that an adverse local tissue reaction may result in some
      patients due to the mechanically assisted crevice corrosion. This article details
      the clinical, radiographic, and laboratory evaluation of patients with these
      components who present with persistent pain. The relevant surgical strategies and
      techniques to address this pathology in symptomatic patients are addressed.

PMID- 22588389
TI  - Altered pharyngeal muscles in Parkinson disease.
AB  - Dysphagia (impaired swallowing) is common in patients with Parkinson disease (PD)
      and is related to aspiration pneumonia, the primary cause of death in PD.
      Therapies that ameliorate the limb motor symptoms of PD are ineffective for
      dysphagia. This suggests that the pathophysiology of PD dysphagia may differ from
      that affecting limb muscles, but little is known about potential neuromuscular
      abnormalities in the swallowing muscles in PD. This study examined the fiber
      histochemistry of pharyngeal constrictor and cricopharyngeal sphincter muscles in
      postmortem specimens from 8 subjects with PD and 4 age-matched control subjects.
      Pharyngeal muscles in subjects with PD exhibited many atrophic fibers, fiber type
      grouping, and fast-to-slow myosin heavy chain transformation. These alterations
      indicate that the pharyngeal muscles experienced neural degeneration and
      regeneration over the course of PD. Notably, subjects with PD with dysphagia had
      a higher percentage of atrophic myofibers versus with those without dysphagia and
      controls. The fast-to-slow fiber-type transition is consistent with abnormalities
      in swallowing, slow movement of food, and increased tone in the cricopharyngeal
      sphincter in subjects with PD. The alterations in the pharyngeal muscles may play
      a pathogenic role in the development of dysphagia in subjects with PD.

PMID- 22588393
TI  - Arthroscopic bone tunnel augmentation for rotator cuff repair.
AB  - Transosseous repair of the rotator cuff has been shown to recreate the anatomic
      rotator cuff footprint in a secure and cost-efficient manner. However, the
      potential for sutures cutting through bone remains a concern with this strategy.
      Devices have been used successfully during open transosseous rotator cuff repair
      to augment the bone tunnels, potentially avoiding suture cut-out through the weak
      bone of the greater tuberosity. Recently, arthroscopic transosseous fixation of
      rotator cuff tears has become an alternative to arthroscopic suture anchor and
      open transosseous techniques. This method is expected to have the same potential
      pitfalls at the bone-suture interface as the open technique. The authors describe
      a technique for rotator cuff repair using a secure method of arthroscopic bone
      tunnel augmentation.

PMID- 22588394
TI  - Sacroiliac joint injuries.

PMID- 22588395
TI  - Prevalence of carpal tunnel syndrome in motorcyclists.
AB  - Carpal tunnel syndrome is prevalent in patients who have a repetitive motion,
      vibration, or pressure exerted on the wrist joint for an extended period of time.
      The prevalence of this condition in the general population is approximately 5%.
      Motorcyclists subject themselves to high levels of vibration from the road and
      use their wrists to control the motorcycle's brakes, gas intake, and gears via
      the handlebars. Under these conditions, the author hypothesized that an increased
      prevalence of carpal tunnel syndrome would be observed in this population.

PMID- 22588396
TI  - Antimicrobial options in the treatment of adult staphylococcal bone and joint
      infections in an era of drug shortages.
AB  - Staphylococcus aureus is the most pathogenic bacterium and the most common cause
      of osteomyelitis, affecting 50% to 70% of cases. Many antistaphylococcal agents
      with varying activity against methicillin-susceptible S aureus and methicillin
      resistant S aureus are available in the US market. This article reviews the most
      common antistaphylococcal agents used in the treatment of bone and joint
      infections in adult patients and focuses on the antimicrobial agent's mechanism
      of action, US Food and Drug Administration-approved indications, place in
      therapy, monitoring parameters, and common side effects.

PMID- 22588397
TI  - Effect of Timing of Surgery in Partially Injured ACLs.
AB  - The purpose of this study was to explore the optimal timing for surgical
      intervention of partially injured anterior cruciate ligaments (ACL). Thirty-eight
      patients were divided into early (n=17) or delayed (n=21) surgery groups based on
      the interval between injury and surgery. Minimum follow-up was 2 years. The
      outcome measures used were the International Knee Documentation Committee score,
      Lysholm knee score, Tegner activity rating, range of motion, and arthrometer
      measurements. The findings of this study indicate that early surgical
      reconstruction of partially ruptured ACLs did not result in arthrofibrosis but
      may prevent secondary loosening of the intact bundles and further meniscal and
      chondral injury.

PMID- 22588398
TI  - Osteochondritis dissecans in an adult.

PMID- 22588399
TI  - Diagnostic medical imaging radiation exposure and risk of development of solid
      and hematologic malignancy.
AB  - Limiting patients' exposure to ionizing radiation during diagnostic imaging is of
      concern to patients and clinicians. Large single-dose exposures and cumulative
      exposures to ionizing radiation have been associated with solid tumors and
      hematologic malignancy. Although these associations have been a driving force in
      minimizing patients' exposure, significant risks are found when diagnoses are
      missed and subsequent treatment is withheld. Therefore, based on epidemiologic
      data obtained after nuclear and occupational exposures, dose exposure limits have
      been estimated. A recent collaborative effort between the US Food and Drug
      Administration and the American College of Radiology has provided information and
      tools that patients and imaging professionals can use to avoid unnecessary
      ionizing radiation scans and ensure use of the lowest feasible radiation dose
      necessary for studies. Further collaboration, research, and development should
      focus on producing technological advances that minimize individual study
      exposures and duplicate studies. This article outlines the research used to
      govern safe radiation doses, defines recent initiatives in decreasing radiation
      exposure, and provides orthopedic surgeons with techniques that may help decrease
      radiation exposure in their daily practice.

PMID- 22588400
TI  - Value of 3-D CT in classifying acetabular fractures during orthopedic residency
      training.
AB  - The complex anatomy of the pelvis and acetabulum have historically made
      classification and interpretation of acetabular fractures difficult for
      orthopedic trainees. The addition of 3-dimensional (3-D) computed tomography (CT)
      scan has gained popularity in preoperative planning, identification, and
      education of acetabular fractures given their complexity. Therefore, the authors
      examined the value of 3-D CT compared with conventional radiography in
      classifying acetabular fractures at different levels of orthopedic training.
      Their hypothesis was that 3-D CT would improve correct identification of
      acetabular fractures compared with conventional radiography.The classic Letournel
      fracture pattern classification system was presented in quiz format to 57
      orthopedic residents and 20 fellowship-trained orthopedic traumatologists. A case
      consisted of (1) plain radiographs and 2-dimensional axial CT scans or (2) 3-D CT
      scans. All levels of training showed significant improvement in classifying
      acetabular fractures with 3-D vs 2-D CT, with the greatest benefit from 3-D CT
      found in junior residents (postgraduate years 1-3).Three-dimensional CT scans can
      be an effective educational tool for understanding the complex spatial anatomy of
      the pelvis, learning acetabular fracture patterns, and correctly applying a
      widely accepted fracture classification system.

PMID- 22588401
TI  - Analysis of initial injury radiographs of occult femoral neck fractures in
      elderly patients: a pilot study.
AB  - Diagnosis of occult hip fractures by initial radiographs remains challenging in
      the emergency department. Previously, the gold standard for accurate diagnosis of
      occult hip fractures was magnetic resonance imaging. This study used initial
      radiographs obtained in the emergency department to evaluate specific signs and
      measurements as diagnostic references for occult femoral neck fractures in
      elderly patients.Initial negative radiographs were reviewed for 2 groups of
      patients: a group with occult femoral neck fractures (n=16) and a group without
      fractures (n=32). Reviews of initial radiographs and all imaging studies were
      performed by a senior orthopedist (C-C.C.) and a radiologist (H-T.W.). Diagnostic
      signs included lateral, medial, anterior, and posterior signs; measurements
      included elevation of the fat pad and external rotation of the femur. The
      prevalence of occult femoral neck fracture was 3.3%. Initial radiographs of
      occult femoral neck fractures were not routinely negative; 14 (87.5%) of 16
      patients with fractures had at least 1 radiographic sign. Using the positive
      lateral or posterior sign as the diagnostic reference, the sensitivity was 0.875
      and the specificity was 0.906. When elevation of the fat pad was ?1.5 mm, the
      sensitivity was 0.867 and the specificity was 0.857 for the diagnosis of occult
      femoral neck fracture.The lateral and posterior signs and elevation of the fat
      pad ?1.5 mm on initial radiographs are recommended as diagnostic references for
      occult femoral neck fracture. These references are clearly defined and may offer
      important information for all clinicians and radiologists in the emergency
      department.

PMID- 22588402
TI  - Combined anterior and lateral approaches for bone tumors of the femoral neck and
      head.
AB  - Few reports in the literature describe the treatment experience of benign lesions
      of the femoral head and neck. Between July 2005 and August 2009, twenty-four
      patients with bone tumor of the femoral neck and head were treated at the
      authors' institution. Fourteen patients had pathological fractures of the femoral
      neck; in the other 10 patients, the bone cortex was involved. Average tumor size
      was 78 cc (range, 45-130 cc). The patients were treated by curettage plus bone
      grafting via an anterior approach (Smith-Petersen incision) and internal fixation
      via a lateral approach (Hardinge approach). Average follow-up was 34 months
      (range, 10-68 months).Average blood loss and operative time were 450 mL and 87
      minutes, respectively. Six patients experienced complications: 2 superficial
      wound infections, 2 immunological rejections, and 2 hollow screw loosenings and
      slight limps at 12 and 16 months postoperatively, respectively. No recurrence or
      other serious complications, such as pathological fracture, ischemic necrosis of
      the femoral head, or joint degeneration, occurred. Average Musculoskeletal Tumor
      Society score for lower extremity function was 29.2 (range, 27-30) at final
      follow-up, and all patients resumed their normal preoperative work and were pain
      free postoperatively, although 1 patient had a slight limp at final follow-up.A
      combination of anterior and lateral approaches may produce good clinical and
      functional results with minimal complications in bone tumors of the femoral neck.

PMID- 22588403
TI  - Treatment of femoral neck fractures with bipolar hemiarthroplasty using a
      modified minimally invasive posterior approach in patients with neurological
      disorders.
AB  - Bipolar hemiarthroplasty is a useful treatment for displaced femoral neck
      fractures in elderly patients. Although uncommon, dislocation is problematic,
      particularly in older patients, and those with neurologic disorders are at an
      increased risk for this complication. Recently, a modified posterior approach to
      the hip intended to enhance hip joint stability by preserving the short external
      rotators was described. Therefore, the dislocation rate was compared after
      bipolar hemiarthroplasty using the modified or standard minimally invasive
      posterior approach.A retrospective analysis was performed of 67 patients older
      than 65 years with displaced femoral neck fractures and neurological disorders
      who underwent bipolar hemiarthroplasty using the modified and standard approaches
      in 28 and 39 hips, respectively. Follow-up averaged 19.3 months. Dislocation
      rates for the treatment and control groups were 0% and 7.7%, respectively
      (P<.01). No significant difference existed in postoperative bleeding, operative
      time, or length of hospital stay between groups. These data suggest a lower
      dislocation rate after bipolar hemiarthroplasty via the modified, short external
      rotator-sparing approach for treating displaced femoral neck fractures in elderly
      patients with neurological disorders.

PMID- 22588404
TI  - Wound complications in joint arthroplasty: comparing traditional and modern
      methods of skin closure.
AB  - Various methods of skin closure exist in joint replacement surgery. Although
      subcuticular skin closure techniques offer an aesthetic advantage over
      conventional skin stapling, no measurable differences have been reported.
      Furthermore, newer barbed sutures, such as the V-Loc absorbable suture (Covidien,
      Mansfield, Massachusetts), theoretically distribute tension evenly through the
      wound and help decrease knot-related complications. The purpose of this study was
      to evaluate whether wound complication rates were (1) lower in V-Loc closure
      cases as theoretically suggested, (2) lower for subcuticular closure vs staples,
      and (3) significantly different for knee and hip joint reconstruction.A
      retrospective chart review was conducted of 278 consecutive cases of primary
      joint reconstruction performed by a single surgeon (L.P.). The study group
      comprised 106 men and 161 women. Average patient age at surgery was 63 years
      (range, 18-92 years), and average body mass index of the cohort was 33.7 kg/m(2)
      (range, 25-51 kg/m(2)). Skin was closed via staple gun or subcuticular stitch (3
      0 Biosyn [Covidien] vs V-Loc). Seven (3.9%) wound complications occurred in 181
      cases closed with staples. Four (7.8%) wound complications occurred in 51 cases
      closed via subcuticular Biosyn suture. Six (13.0%) wound complications occurred
      in 46 cases closed with V-Loc suture. The staple group had a lower rate of
      complications when compared with the suture group as a whole (P=.033) and when
      compared specifically with the V-Loc suture group (P=.017).

PMID- 22588405
TI  - Clinical Outcomes After Computer-assisted Versus Conventional Total Knee
      Arthroplasty.
AB  - The purpose of this study was to determine whether the use of computer-assisted
      surgery can improve the clinical results in total knee arthroplasty (TKA)
      compared with conventional methods of TKA.A literature search of PubMed (1966 to
      August 2011), CENTRAL (Cochrane Controlled Trials Register; issue 3, 2011), and
      EMBASE (1984 to August 2011) was conducted. Randomized, controlled trials
      detecting the clinical outcomes of TKA with or without the use of computer
      assisted surgery were identified. A meta-analysis of these clinical trials was
      then performed. Twenty-one articles were included in the meta-analysis. The
      results confirmed that operative time was significantly increased with the use of
      computer-assisted TKA (mean standard difference, 14.68; 95% confidence interval
      [CI], 11.74 to 17.62; P<.00001], whereas no significant difference existed
      between the 2 groups regarding the total operative blood loss (mean standard
      difference, -54.38; 95% CI, -119.76 to 11.00; P=.10). As for other clinical
      outcomes, including the Knee Society Score (mean standard difference, 4.47; 95%
      CI, -1.05 to 9.99; P=.36) and range of motion (mean standard difference, 1.38;
      95% CI, -1.43 to 4.18; P=.34), the use of computer-assisted TKA did not help to
      improve function recovery postoperatively.

PMID- 22588406
TI  - Effect of PEEK polymer on tunnel widening after hamstring ACL reconstruction.
AB  - The purpose of this study was to evaluate the effect of the AperFix device
      (Cayenne Medical, Inc, Scottsdale, Arizona), composed of polyetheretherketone
      (PEEK) polymer, on tunnel widening after hamstring anterior cruciate ligament
      (ACL) reconstruction as compared with 2 other fixation devices: the TransFix
      (Arthrex, Inc, Naples, Florida) and the EndoButton (Smith & Nephew Endoscopy,
      Mansfield, Massachusetts). Sixty-seven patients with isolated total ACL ruptures
      who underwent arthroscopically assisted reconstruction using hamstring autografts
      at the authors' institution were included in the study. Patients were assigned
      into 1 of 3 groups in a nonrandomized fashion: AperFix (n=18), TransFix (n=29),
      and EndoButton (n=20). Mean follow-up was 30 months. Tunnel widening measurements
      were performed on anteroposterior and lateral digital plain radiographs taken in
      postoperative week 1 and at final follow-up. Laxity testing, Lysholm scoring, and
      arthrometric evaluation were performed.All 3 graft fixation devices resulted in
      significant tunnel widening in both tibial and femoral tunnels at final follow-up
      when compared with the immediate postoperative period. Tunnel widening between
      groups was not significantly different in terms of coronal and sagittal femoral
      tunnel diameters. Tibial tunnel diameter increase in the sagittal plane in the
      EndoButton group was significantly smaller than that in the TransFix and AperFix
      groups. No correlation was found between the amount of tunnel enlargement and
      clinical outcomes of ACL surgery. This study's findings suggest that tunnel
      enlargement after ACL reconstruction is influenced by the type of graft fixation
      on the tibial side irrespective of clinical outcome, and PEEK polymer does not
      have an effect on tunnel widening after hamstring ACL reconstruction.

PMID- 22588407
TI  - Pain management after total knee arthroplasty using a multimodal approach.
AB  - Improvements in pain management techniques over the past decade have had a
      significant impact on the outcomes of total knee arthroplasty. Of these
      techniques, multimodal approaches have shown potential. The purpose of this study
      was to compare the results of periarticular injection (PAI) to a combination of
      patient-controlled epidural analgesia and femoral nerve block (PCEA/FNB). Ninety
      patients undergoing primary unilateral total knee arthroplasty between June 2010
      and March 2011 were randomized into 2 groups. The first group received the
      PCEA/FNB protocol, whereas the second group received the PAI. Mean patient age
      was 66.1 +/- 8.7 years. All patients were operated on using a similar standard
      medial parapatellar approach, and all received preemptive analgesia and
      postoperative pain protocols. All patients were interviewed twice daily for the
      first 3 days postoperatively, once on day 7, and once in month 6. The 2 groups
      had similar readiness for discharge (PCEA/FNB group, 3.3 +/- 1.2 days; PAI group,
      3.2 +/- 1.9 days). The results indicated no statistical difference between the 2
      groups in 3 of 4 categories (rest in the morning, rest in the evening, and
      ambulation in the morning). Pain on ambulation was the only category that was
      statistically lower in the PCEA/FNB group than in the PAI group.Although the
      study demonstrates similar results between the 2 groups, PAI can play a major
      role in postoperative pain control in institutions that may not have
      appropriately trained individuals, equipment, and resources for PCEA/FNB. It also
      reduces many of the side effects and complications associated with regional
      anesthesia.

PMID- 22588408
TI  - One-step articular cartilage repair: combination of in situ bone marrow stem
      cells with cell-free poly(L-lactic-co-glycolic acid) scaffold in a rabbit model.
AB  - Focal full-thickness articular cartilage defects are challenging to repair. The
      purpose of this study was to find a simple, effective 1-step articular cartilage
      repair method. Because stem cell niches produce a microenvironment for stem cell
      self-renewal, proliferation, and differentiation, we integrated in situ bone
      marrow stem cells with an implanted poly(L-lactic-co-glycolic acid) (PLLGA)
      scaffold. Marrow stem cells grew and proliferated on cell-free PLLGA scaffolds,
      which were evaluated by scanning electronic microscopy (SEM) and Cell Counting
      Kit-8 (Dojindo, Kumamoto, Japan). Twenty-seven rabbits (54 knees) with large
      cylinder femoral trochlear cartilage defects were created and repaired with
      microfracture and cell-free PLLGA scaffold implantation (group 1), microfracture
      (group 2), or cell-free PLLGA scaffold implantation (group 3).Outcomes were
      evaluated by magnetic resonance imaging, International Cartilage Repair Society
      scores, histology, and immunohistochemistry. The repair effects were better in
      group 1 than in groups 2 and 3. In group 1, hyaline-like cartilage formed at week
      24. Magnetic resonance imaging showed homogeneous signals as the adjacent normal
      cartilage. Collagen type II and toluidine blue were stained positively as normal
      cartilage tissue, and the color and thickness of regenerated tissue were similar
      to surrounding normal tissue. The combination of microfracture and cell-free
      PLLGA scaffold implantation used endogenous marrow stem cells in situ and
      promoted hyaline-like cartilage regeneration rapidly and effectively.

PMID- 22588409
TI  - Reconstruction of the extensor mechanism after major knee resection.
AB  - In periarticular knee resections, the relative lack of soft tissue coverage and
      need to reattach the extensor mechanism after en bloc resection of the tibial
      tuberosity with the tumor specimen complicate reconstructions and decrease
      postoperative function and stability of the knee joint. Distal femoral
      reconstructions are less problematic; muscular attachments are relatively few,
      neurovascular structures are not immediately adjacent to bone, and the knee
      extensor mechanism is usually not compromised from bone tumors. In the proximal
      tibia, the close proximity of the neurovascular structures in the popliteal fossa
      and peroneal nerve at the lateral aspect of the leg make reconstruction more
      difficult. Poor function is mostly related to unreliable options for knee
      extensor mechanism reattachment and poor soft tissue coverage. Successful and
      reliable attachment of the soft tissues has been a significant advance that
      improved functional outcomes.This article describes techniques for the
      reconstruction of the extensor mechanism of the knee after proximal tibia
      resections. Combined reconstruction techniques using direct reattachment of the
      patellar tendon with synthetic materials to megaprosthetic or allograft
      reconstructions for immediate stability, augmentation with autologous bone graft
      or substitutes at the attachment site, and coverage with the medial gastrocnemius
      muscle flap and supplementary flaps for long-term stability of the reattachment
      are currently considered the gold standard.

PMID- 22588410
TI  - Functional Outcomes in High-function-demand patients after total knee
      arthroplasty.
AB  - Total knee arthroplasty is a safe last-resort treatment for osteoarthritis that
      has excellent results in low-function-demand elderly patients. Current implants
      offer the same results in high-function-demand patients. However, supportive data
      do not exist.One-year Krackow Activity Scores (KAS) of 552 patients from 2
      prospective studies were used to retrospectively determine low- and high-function
      demand populations. Low function demand was defined as a KAS between 1 and 9
      points, and high function demand was defined as a KAS between 10 and 18 points.
      Patients were assessed preoperatively and at 6 weeks, 3 months, and 1 and 2 years
      postoperatively per the Knee Society Score-function domain, KAS, SF-36, range of
      motion, and pain. Comparability between groups was tested for demographics and
      comorbidities.Both groups showed significant improvement in function, range of
      motion, and pain 2 years postoperatively. High-function-demand patients had
      comparable improvement in function compared with low-function-demand patients.
      Excellent function can be achieved in high-function-demand patients.

PMID- 22588411
TI  - MRI appearance of presumed self-inflicted trauma in the knees of military
      recruits.
AB  - When knee bone marrow edema is observed on magnetic resonance imaging (MRI), it
      usually follows a pattern that can be explained by certain etiologies. This
      article describes a series of unusual knee bone marrow edemas in soldiers
      presumed to represent self-inflicted trauma.Ten soldiers (9 men and 1 woman; age
      range, 19-24 years) underwent knee MRI. None reported recent trauma or stress,
      and all presented with nonspecific pain or failure to respond to therapy. All
      showed a similar unusual pattern of bone marrow edema in the medial femoral
      condyle. Three observers evaluated the location of the bone marrow edema within
      the medial femoral condyle and its distance from the articular surface,
      dimensions, overlying soft tissue abnormality, and internal derangements. The
      edema was always subcortical and located in the middle aspect (n=7) or mid
      anterior aspect (n=3) of the medial femoral condyle but was never centered
      subarticularly. Edema size ranged between 8 * 10 * 8 and 32 * 46 * 40 mm.
      Overlying soft tissue abnormalities were common (n=4) and included organizing
      (n=1) and residual hematoma (n=3). Concomitant MRI abnormalities were seen in 3
      patients, usually minor. Eight patients reported longstanding pain with no
      antecedent trauma, and 2 reported remote trauma. One patient had a negative 4
      month follow-up MRI, and another had a negative arthroscopy. Poor correlation
      existed between MRI findings and the absence of stress and trauma. Soldier chat
      rooms were found that describe how to induce fractures at this location.

PMID- 22588412
TI  - Comparison of dynamic and locked compression plates for treating midshaft
      clavicle fractures.
AB  - The purpose of this study was to compare the parameters of perioperative course
      and cost-effectiveness for patients with midshaft clavicle fractures treated by
      dynamic compression plates or locked compression plates.This retrospective, case
      controlled study involved 54 patients with midshaft clavicle fractures who
      received dynamic compression plates (n=21) or locked compression plates (n=33)
      between January 2002 and December 2008. Indications for surgery included
      displacement or shortening >2 cm, comminuted fractures, and skin tenting.
      Patients with previous malunion, nonunion, multiple injuries of the shoulder
      girdle, or open fractures were excluded. Preoperative demographics showed no
      statistically significant differences between the 2 groups. Eighteen patients
      with dynamic compression plates and 28 patients with locked compression plates
      with postoperative follow-up >1 year were included for comparison. Statistical
      analyses for operative time, blood loss, complication rate, hospital stay, and
      union rate demonstrated no statistically significant difference between the 2
      groups. The only statistically significant difference was a higher rate of plate
      removal requests in the dynamic compression plate group. Considering medical
      expenditure, locked compression plates cost 6 times more than dynamic compression
      plates in the authors' institution (US $600 vs $100, respectively).Other than
      more plate removal requests in the dynamic compression plate group and greater
      expense in the locked compression plate group, dynamic compression plates and
      locked compression plates achieved satisfactory operative outcomes in treating
      midshaft clavicle fractures, with no statistically significant difference between
      perioperative course and eventual fracture union observed between the 2 groups.

PMID- 22588413
TI  - Hemiarthroplasty versus reverse total shoulder arthroplasty for acute proximal
      humerus fractures in elderly patients.
AB  - Proximal humerus fractures are the third most common fracture in elderly
      patients. Hemiarthroplasty has been the treatment of choice in patients with bone
      quality and fracture patterns not amenable to open reduction and internal
      fixation. Reverse total shoulder arthroplasty is a newer option that appears to
      be less dependent on tuberosity healing than hemiarthroplasty. The authors
      hypothesized that reverse total shoulder arthroplasty provides improved
      functional outcomes compared with hemiarthroplasty for fractures in elderly
      patients.A retrospective review was performed of all patients treated with
      arthroplasty for acute proximal humerus fractures in an orthopedic practice using
      a Current Procedural Terminology code search, patient charts, and radiographs.
      Validated outcome scores were used to assess satisfaction, function, and general
      well-being. Twenty-three patients were treated for acute proximal humerus
      fractures (11 reverse total shoulder arthroplasties and 12 hemiarthroplasties).
      Three patients were lost to follow-up, and 6 patients were deceased. Mean follow
      up was 3.6 years (range, 1.3-8 years). Reverse total shoulder arthroplasty
      outperformed hemiarthroplasty with regard to forward flexion, American Shoulder
      and Elbow Society score, University of Pennsylvania shoulder score, and Single
      Assessment Numerical Evaluation score.Reverse total shoulder arthroplasty is a
      reliable option for acute, proximal humerus fractures that are not amenable to
      closed treatment or reconstruction in elderly patients. Improved functional
      outcomes when compared with hemiarthroplasty must be balanced against the
      increased cost and limited life expectancy of patients with this injury.

PMID- 22588414
TI  - New classification system for long-bone fractures supplementing the AO/OTA
      classification.
AB  - This article describes a novel, clinically oriented classification system for
      long-bone fractures that is simple, reliable, and useful to predict treatment
      method, complications, and outcome. The reliability and memorability of the new
      classification were statistically tested and compared with the AO
      Muller/Orthopaedic Trauma Association (AO/OTA) long-bone fracture classification.
      The proposed classification system was also clinically validated with a targeted
      pilot study designed for content and clinical outcome retrospectively reviewing
      122 closed tibial shaft fractures, which were used as a representative paradigm
      of long-bone fractures. Statistical evaluation showed that the proposed
      classification system had improved inter- and intraobserver variation agreement
      and easier memorability compared with the AO/OTA classification system. The
      clinical validation study showed its predictive value regarding selection of
      treatment method, complication rate, and injury outcome.The proposed
      classification system proved simple, reliable, and memorable. Its clinical value
      appeared strong enough to justify the organization of larger studies for a
      complete assessment of its clinical usefulness for all long-bone fractures.

PMID- 22588415
TI  - Functional disabilities and issues of concern for Asian patients before total
      ankle arthroplasty.
AB  - Total ankle arthroplasty is a commonly performed invasive procedure that can be
      distressing to patients. Therefore, surgeons should consider patients' issues of
      greatest interest and concerns at the time of surgery and the function that
      patients hope to recover. Many studies have reported surgeon concerns before
      total knee arthroplasty and total hip arthroplasty, but few have focused on
      patients. The purpose of this study was to evaluate patients' functional
      disabilities and issues of concern regarding total ankle arthroplasty.Between May
      2008 and June 2010, eighty-five patients (52 men and 33 women; mean age, 60
      years) were recruited for the study. All patients were asked to complete a
      questionnaire divided into 3 parts: sociodemographic data, current functional
      disabilities and their perceived importance, and issues concerning patients
      before total ankle arthroplasty. Regarding functional disability based on
      severity, the top 5 issues were limping, difficulty squatting, daytime pain,
      difficulty kneeling, and difficulty climbing stairs. Regarding functional
      disability based on perceived importance, the top 5 issues were daytime pain,
      limping, difficulty walking, difficulty kneeling, and difficulty working.
      Regarding issues of concern, the top 5 issues were pain intraoperatively, ability
      to walk as much as desired, ability to climb stairs, pain after discharge from
      the hospital, and pain immediately postoperatively. The most important issue
      before total ankle arthroplasty was pain. Patients had a strong interest in high
      ankle extension and increased range of motion due to the lifestyle and religious
      activities of Eastern populations.

PMID- 22588416
TI  - Analysis of NHSLA claims in orthopedic surgery.
AB  - National Health Service (NHS) statistics in the United Kingdom demonstrate an
      increase in clinical negligence claims over the past 30 years. Reasons for this
      include elements of a cultural shift in attitudes toward the medical profession
      and the growth of the legal services industry. This issue affects medical and
      surgical health providers worldwide.The authors analyzed 2117 NHS Litigation
      Authority (NHSLA) orthopedic surgery claims between 1995 and 2001 with respect to
      these clinical areas: emergency department, outpatient care, surgery (elective or
      trauma operations), and inpatient care. The authors focused on the costs of
      settling and defending claims, costs attributable to clinical areas, common
      causes of claims, and claims relating to elective or trauma surgery. Numbers of
      claims and legal costs increased most notably in surgery (elective and trauma)
      and in the emergency department. However, claims are being defended more
      robustly. The annual cost for a successful defense has remained relatively
      stable, showing a slight decline. The common causes of claims are postoperative
      complication; wrong, delayed, or failure of diagnosis; inadequate consent; and
      wrong-site surgery. Certain surgical specialties (eg, spine and lower-limb
      surgery) have the most claims made during elective surgery, whereas upper-limb
      surgery has the most claims made during trauma surgery.The authors recommend that
      individual trusts liaise with orthopedic surgeons to devise strategies to address
      areas highlighted in our study. Despite differences in health care systems
      worldwide, the underlying issues are common. With improved understanding,
      physicians can deliver the service they promise their patients.

PMID- 22588417
TI  - Postresurfacing periprosthetic femoral neck fractures: nonoperative treatment.
AB  - Femoral neck fractures after total hip resurfacing procedures occur infrequently
      but require immediate orthopedic intervention. Historically, they have been
      treated by conversion to traditional total hip arthroplasty. However, to the
      authors' knowledge, no treatment algorithm has ever been described. The authors
      have directly treated or consulted on 13 cases of periprosthetic femoral neck
      fractures after metal-on-metal hip resurfacing arthroplasties that were
      successfully treated nonoperatively: all fractures healed with protected weight
      bearing, producing excellent clinical results. Two cases are described in detail,
      and the authors propose a classification system that can assist the orthopedist
      in choosing the treatment regimen. Type I fractures are nondisplaced and should
      be initially treated nonoperatively with a course of protected weight bearing. If
      successful, the overall success of the resurfacing should not be compromised.
      Partially displaced, or type II, fractures may heal with nonoperative management.
      However, if the components have shifted, it may affect the long-term durability
      of the arthroplasty and eventually result in premature conversion to a
      traditional total hip replacement. Depending on the position of the components,
      it may also have an effect on the ion generation potential of the metal-on-metal
      articulation. This treatment pathway can be undertaken only with a full and
      detailed explanation of all of the possible complications and outcomes with the
      patient. Completely displaced, or type III, fractures require immediate
      conversion to total hip arthroplasty.

PMID- 22588418
TI  - Minocycline-induced black bone disease encountered during total knee
      arthroplasty.
AB  - Finding discolored bone intraoperatively can be confusing and concerning to
      orthopedic surgeons. Multiple causes of pigmented bone exist, including
      ochronosis, metabolic bone diseases, metal deposits, sequestrum, metastatic
      disease, and minocycline use. Bone quality is an important consideration in
      intraoperative decision making with respect to components and fixation options in
      total joint arthroplasty. Abnormal bone encountered in routine arthroplasty can
      raise concerns over the integrity and healing potential of the bone when the
      etiology is uncertain.Minocycline is a drug routinely used for the treatment of
      acne, rosacea, and rheumatoid arthritis. Pigmentation is a commonly recognized
      adverse reaction associated with most of the drugs in the tetracycline family,
      affecting the skin, nails, teeth, oral mucosa, bones in the oral cavity, ocular
      structures, cartilage, thyroid, and other visceral structures.This article
      describes a case of pigmented bone secondary to minocycline use in a 55-year-old
      woman undergoing total knee arthroplasty. This entity has rarely been documented
      in the orthopedic literature; however, orthopedic surgeons should be aware of
      this side effect secondary to the widespread use of minocycline. Questions
      concerning the effect of minocycline on bone metabolism and structural integrity
      have yet to be fully answered, but an understanding and recognition of the entity
      will help guide surgeons with intraoperative decision making.

PMID- 22588419
TI  - Misdiagnosis of an atypical cyclops lesion 4 years after single-bundle anterior
      cruciate ligament reconstruction.
AB  - Development of a cyclops lesion is a well described complication after anterior
      cruciate ligament (ACL) reconstruction. It commonly results in gradual extension
      loss during the early postoperative course, and magnetic resonance imaging (MRI)
      of the soft tissue nodule attached to the ACL graft is needed. Cyclops lesions
      are easy to diagnose based on the symptoms and MRI findings. Previous study
      showed that 78.6% of cyclops lesions had extension loss within 6 weeks
      postoperatively, and the diagnosis of 92.8% cases of cyclops lesions was
      established within 6 months.This article describes a case of misdiagnosis of a
      cyclops lesion 4 years after ACL reconstruction as a meniscal lesion combined
      with a meniscal cyst. The patient was asymptomatic for 4 years and then presented
      with a locked left knee and pain at the inferior pole of the patella during an
      attempt to gently extend the knee. Magnetic resonance imaging revealed a lateral
      meniscal cyst. The knee locking was released suddenly 2 days preoperatively. The
      authors had attributed the missed diagnosis to an atypical history and symptoms
      and an associated meniscal cyst.The purpose of this article is to help prevent
      misdiagnosis of atypical cyclops lesions. Cyclops lesions should be considered in
      the differential diagnosis of patients who present with gradual or sudden loss of
      extension after ACL reconstruction, regardless of how much time has passed
      postoperatively.

PMID- 22588420
TI  - Osteoarticular allograft reconstruction for hill-sachs lesion in an adolescent.
AB  - Glenoid and humeral head bone loss is the most common cause of failure after
      surgical shoulder instability stabilization. Large Hill-Sachs lesions involving
      >30% of the articular surface of the humeral head typically occur after neglected
      or locked shoulder dislocations. Such large lesions may require osteochondral
      allograft reconstruction or prosthetic replacement to regain shoulder stability
      and function.Previous reports of osteochondral allograft reconstruction have
      focused on adults. This article describes a case of a 16-year-old autistic boy
      who sustained an anterior dislocation of the right shoulder following a seizure
      episode. The dislocation was diagnosed 12 days later as a progressive deformity,
      and his parents noticed his inability to use his upper extremity. The patient had
      a large (30%) humeral head Hill-Sachs lesion and persistent anterior shoulder
      instability after initial closed reduction. He underwent an open osteochondral
      allograft reconstruction for the restoration of the humeral head articular
      surface. The sizing of the defect, matching harvest of the allograft, and perfect
      fit of the allograft to the defect are critical steps to ensure congruent
      restoration of the humeral head. The allograft was stabilized in the defect of
      the humeral head using cancellous screws placed from below the articular surface.
      Radiographs 20 months postoperatively showed complete incorporation of the
      osteochondral allograft. At 30 months postoperatively, his shoulder was stable
      and functional.

PMID- 22588421
TI  - Fly Fishing-related lesser tuberosity avulsion in an adolescent.
AB  - Stress lesions of the shoulder in athletic and active adolescents are most
      commonly associated with overhead sports. One of the most uncommon stress lesions
      of the shoulder in adolescents is an avulsion of the lesser tuberosity of the
      proximal humerus. To our knowledge, only 2 other cases of lesser tuberosity
      avulsions from repetitive motion have been reported, both of which were secondary
      to baseball pitching.This article describes a case of an isolated partial
      avulsion of the lesser tuberosity of the humerus in an adolescent as a result of
      repetitive stress from fly fishing. The patient had no symptoms in his shoulder
      until after casting for approximately 10 hours a day for 3 days. He presented
      with anterior shoulder pain that worsened with abduction and external rotation.
      On examination, he had tenderness over the lesser tuberosity and pain with
      subscapularis muscle testing, such as the lift-off test. He had a negative
      apprehension sign but no signs of a superior labrum tear. Conventional
      radiography with an axillary view confirmed the diagnosis. He recovered with rest
      and gradual return to activities. Two years after injury, the patient had no
      limitations functionally, and his shoulder examination was normal.This case
      highlights the importance of being aware that (1) this lesion can occur in
      activities other than baseball, (2) characteristic physical findings exist with
      this lesion, (3) obtaining an axillary radiograph can confirm diagnosis, and (4)
      these avulsions can be treated successfully with nonoperative interventions.

PMID- 22588422
TI  - Anatomical reconstruction of reverse hill-sachs lesions using the underpinning
      technique.
AB  - Posterior glenohumeral joint dislocation is an uncommon injury and is associated
      with bony and ligamentous disruption. It requires prompt diagnosis and early
      treatment to prevent acute or recurrent instability and subsequent dysfunction.
      Reverse Hill-Sachs lesions associated with this injury are challenging to treat,
      and optimal treatment is controversial. Treatment methods can be divided into
      those that achieve stability through muscle transfers, osteotomies, or posterior
      bone-block procedures (glenoid augmentation) and those that restore the
      sphericity of the humeral head. Joint replacement is often suggested for large
      head lesions (>50%) considered beyond reconstruction. Restoration of stability,
      preservation of the proximal humeral anatomy, and salvage of the humeral head
      sphericity should be the treatment goals in the younger population.This article
      describes the surgical technique of elevation of the impressed osteochondral
      fragment followed by filling the lesion with Allomatrix bone graft putty (Wright
      Medical Technology, Arlington, Tennessee) in 2 patients. The size of the head
      lesion was <=35%. Underpinning raft screws were used to provide subchondral
      support and prevent the collapse of the elevated fragment. Postoperatively, the
      sphericity of the humeral head and glenohumeral stability were restored. No
      evidence of collapse, osteonecrosis, or osteoarthritis progression was seen at
      latest follow-up. Functional results were excellent, with a minimum follow-up of
      2 years.This technique is an alternative method of restoring humeral head
      sphericity in patients with acute posterior glenohumeral joint dislocations with
      medium (20%-40%) reverse Hill-Sachs lesions.

PMID- 22588423
TI  - Zone 2 flexor digitorum profundus and superficialis rupture treated with single
      stage tendon reconstruction using an Active Hunter Rod Implant.
AB  - To our knowledge, no report has been published of a flexor tendon rupture as a
      result of a closed phalangeal fracture.A 58-year-old woman with multiple medical
      comorbidities presented with a closed, apex volar fracture of her long finger
      proximal phalynx with clinically intact flexor digitorum profundus and
      superficialis tendons in zone 2 of the flexor tendon sheath. After 5 weeks of
      nonoperative treatment, the patient reported hearing a pop in her finger, and
      clinical findings suggested rupture of the flexor digitorum profundus and
      superficialis tendons. Intraoperatively, the nonreparable attritional rupture was
      underneath the A2 pulley. A bony prominence in the tendon sheath floor from the
      healed phalynx fracture made rerupture a concern with a tendon graft. A Hunter
      Active Tendon Implant (Wright Medical Technology, Inc, Arlington, Tennessee) was
      used to reconstruct the flexor digitorum profundus tendon to avoid a second
      procedure. The patient progressed well and had regained a functional arc of
      active finger range of motion by 2 months postoperatively.The Hunter Active
      Tendon Implant provided a suitable alternative to a 2-staged procedure, with the
      added benefit that a good tendon bed was developed in the event that a second
      procedure was needed.

PMID- 22588424
TI  - Stingray injury to the webspace of the foot.
AB  - Stingrays are cartilaginous fish that are related to sharks. They are one of the
      largest groups of venomous marine animals. Stingrays account for 750 to 2000
      injuries annually. They are generally passive, reclusive creatures that only
      sting in self-defense. Most injuries caused by these animals are nonfatal. A
      stingray possesses between 1 and 4 venomous stings, which are located along the
      caudal spine. If a stingray injury is sustained, parts of the spine may be left
      in the lacerations, which prolongs exposure to venom and increases the risk of
      subsequent wound infection. Stingray venom is unique in its enzymatic composition
      and results in distinct soft tissue injury patterns. Typically, a pattern of
      acute inflammation occurs, with a predominantly lymphoid cellular infiltrate
      followed by necrosis. The environment in which stingray injuries occur presents
      unique bacterial flora, and subsequent wound infections require careful
      antibiotic selection.This article describes a case of a healthy 31-year-old woman
      who sustained a stingray injury to the webspace of the foot while in Costa Rica.
      Initial basic first aid measures were applied. However, the wound subsequently
      became infected, and formal irrigation and debridement were performed. The
      initial wound cultures grew Staphylococcus viridans. Two months postoperatively,
      the incision was well healed, and the patient was pain free and returned to work.

PMID- 22588425
TI  - Prosthesis-free solution for below-knee amputations.
AB  - The Ilizarov fixator can be used as a bone regenerator to correct limb-length
      discrepancies in patients who require limb lengthening.A 17-year-old man
      presented with 12 cm of left lower-limb shortening and amputation at the left mid
      forefoot region, which was the result of severe burns of the left lower limb at 2
      years of age. The burns damaged the distal femoral, proximal, and distal tibial
      physes. Scarring around knee and leg acted as a bowstring and slowed normal
      longitudinal femoral and tibial bone growth. The patient wished to be prosthesis
      free. Limb lengthening was performed with the Ilizarov fixator. The patient
      became prosthesis free and was able to perform activities of daily living wearing
      normal footwear, which was possible because the patient had a good heel pad. The
      patient can walk on a normal limb with no prosthesis, the significant advantage
      being the right proprioceptive feedback it gives the patient during ambulation
      because it is sensate.This technique can be used in other patients with below
      knee amputations in which the tibial amputated end can be given a myoplasty cover
      or padding nearly as good as a heel. Subsequently, tibiae can be lengthened, and
      patients can be made to bear weight on artificial heels.

PMID- 22588426
TI  - Intraspinal penetrating stab injury to the middle thoracic spinal cord with no
      neurologic deficit.
AB  - The annual incidence of traumatic spinal cord injury worldwide is estimated to be
      35 patients per million. Nonmissile penetrating spinal injuries most commonly
      occur in the thoracic region, and the majority has neurologic deficits on
      admission. The management of patients who lack neurologic deficits is
      controversial due to the risk of neurologic status alteration intraoperatively.
      However, failure to intervene increases the risk of infection, delayed onset of
      neurologic deficits, and worsening functional outcome.A 17-year-old boy presented
      with an intradural T7-T8 knife penetration injury to the spinal cord with no
      neurologic deficit. Rapid surgical intervention was critical because the knife
      was lodged between the 2 hemispheres of the spinal cord. The patient was
      intubated in the lateral position, transferred to the prone position on a Jackson
      table, and underwent surgical decompression with laminectomy 1 level above and
      below the injury site, removal of the knife blade in the original path of
      trajectory, and repair of the dural tear with a collagen matrix. The patient
      sustained no neurologic sequelae from the penetrating knife injury. He was able
      to ambulate at discharge and had no complications. To our knowledge, this is the
      only report of a patient with intradural spinal cord penetration by a foreign
      object (knife blade) presenting with a normal neurologic preoperative examination
      that persisted throughout the course of postoperative care.

PMID- 22588427
TI  - Thoracic disk herniation with paraparesis treated with transthoracic
      microdiskectomy in a 14-year-old girl.
AB  - Herniated thoracic intervertebral disk causing spinal cord compression with
      paraparesis is uncommon in adults and rare in children. This article describes a
      case of pediatric thoracic disk herniation with paraparesis treated surgically.A
      14-year-old girl presented with a 4-month history of diffuse back pain and sudden
      onset paraparesis. Motor strength was 4/5 in both legs, and she had lost the
      ability to ambulate. Magnetic resonance imaging revealed spinal cord compression
      due to a herniated intervertebral disk at T5-T6. Computed tomography scan after
      myelogram demonstrated anterior dural sac compression at T5-T6 but no
      intervertebral disk calcification. She underwent transthoracic microdiskectomy.
      The herniated disk was removed, and the thoracic spinal cord was decompressed. No
      fusion was performed after microdiskectomy. The postoperative course was
      uncomplicated, and neurologic deficit resolved within 2 weeks postoperatively.
      The patient was pain free with no neurologic deficit at 24-month follow-up, and
      computed tomography scan showed remodeling of the T5 and T6 vertebral bodies.Most
      cases of thoracic disk herniation are asymptomatic. If no compression of the
      spinal cord exists, the natural history of the disease justifies conservative
      management. Although the treatment of choice is conservative, surgery is required
      in patients who develop progressive neurologic deficit or severe radicular pain.
      Transthoracic microdiskectomy without fusion is considered a treatment in similar
      cases.

PMID- 22588428
TI  - Facial selectivity induced by N-aryl atropisomerism in benzonitrile oxide
      cycloadditions with 4-methylene-2-oxazolidinones.
AB  - N-Aryl 4-methylene-2-oxazolidinones, prepared via the corresponding O-propargyl
      carbamates, underwent nitrile oxide cycloaddition with benzonitrile oxide to give
      5-spiro isoxazoline adducts with complete regioselectivity. Steric hindrance by
      atropisomerism around the N-aryl bond induced facial selectivity in these
      cycloadditions.

PMID- 22588429
TI  - Disaster mobile health technology: lessons from Haiti.
AB  - INTRODUCTION: Mobile health (mHealth) technology can play a critical role in
      improving disaster victim tracking, triage, patient care, facility management,
      and theater-wide decision-making. PROBLEM: To date, no disaster mHealth
      application provides responders with adequate capabilities to function in an
      austere environment. METHODS: The Operational Medicine Institute (OMI) conducted
      a qualitative trial of a modified version of the off-the-shelf application iChart
      at the Fond Parisien Disaster Rescue Camp during the large-scale response to the
      January 12, 2010 earthquake in Haiti. RESULTS: The iChart mHealth system created
      a patient log of 617 unique entries used by on-the-ground medical providers and
      field hospital administrators to facilitate provider triage, improve provider
      handoffs, and track vulnerable populations such as unaccompanied minors, pregnant
      women, traumatic orthopedic injuries and specified infectious diseases.
      CONCLUSION: The trial demonstrated that even a non-disaster specific application
      with significant programmatic limitations was an improvement over existing
      patient tracking and facility management systems. A unified electronic medical
      record and patient tracking system would add significant value to first responder
      capabilities in the disaster response setting.

PMID- 22588430
TI  - Demographic and clinical features of gout patients in Turkey: a multicenter
      study.
AB  - Gout results from multifactor interactions between gender, age, genetic and
      environmental factors. Environmental factors underlying gout and precipitating
      factors triggering acute attacks might vary in different populations with
      different lifestyles. In this study, we aimed to collect data regarding the
      demographic and clinical features, comorbid factors, and precipitating factors
      associated with the initiation of acute attacks in gout patients in Turkey. A
      total of 312 patients were included in this study (mean age, 58.8 +/- 13.8 years;
      female/male ratio, 55/257). The demographic features, alcohol intake, clinical
      and laboratory features, and comorbid conditions including obesity, diabetes
      mellitus, hyperlipidemia, hypertension, and coronary heart disease were noted in
      a standard questionnaire. Precipitating factors initiating acute attacks (if any)
      were also noted. The patients were divided into 4 groups according to the region
      of location as central Anatolian region, southeast Anatolian region, Aegean
      region, and Trakya region. Our results were compared according to the gender and
      the location of the patients. The mean age at the start of the symptoms was 10
      years higher in women (60.4 +/- 14.8 and 50.6 +/- 13.5 years in women and men,
      respectively, p < 0.001).Obesity was present in 40.1 %, diabetes mellitus in 17.9
      %, hyperlipidemia in 30.1 %, hypertension in 53.5 %, coronary artery disease in
      17 %, and nephrolithiasis in 21.8 % of patients. Precipitating factors triggering
      gout flares were as follows: diet (high consumption of meat or fish) in 46.5 %,
      alcohol consumption in 15.7 %, diuretics in 8.3 %, diet or diuretics in 5.1 %,
      diet or alcohol in 4.5 %, diet or alcohol or diuretics in 1.6 %, others in 4.2 %,
      and none in 14.1 %. The presence of diabetes and diuretic use was more common
      among women. Use of diuretics is a more common trigger for gout flares among
      women. On the other hand, various comorbid conditions, such as obesity and
      hypertension, and triggers for gout flares may differ between patients living in
      different geographic regions. In summary, we reported the first data regarding
      clinical and demographic characteristics of gout in Turkey. The majority of our
      patients could describe at least one "trigger" that initiated gout flare. Both
      comorbid conditions and triggers of attack might differ between men and women,
      and in different geographic areas. Better knowledge of the modifiable risk
      factors can be useful for the management strategy to optimize long-term patient
      outcomes in local clinics.

PMID- 22588431
TI  - Visualization of cortex organization and dynamics in microorganisms, using total
      internal reflection fluorescence microscopy.
AB  - TIRF microscopy has emerged as a powerful imaging technology to study spatio
      temporal dynamics of fluorescent molecules in vitro and in living cells. The
      optical phenomenon of total internal reflection occurs when light passes from a
      medium with high refractive index into a medium with low refractive index at an
      angle larger than a characteristic critical angle (i.e. closer to being parallel
      with the boundary). Although all light is reflected back under such conditions,
      an evanescent wave is created that propagates across and along the boundary,
      which decays exponentially with distance, and only penetrates sample areas that
      are 100-200 nm near the interface. In addition to providing superior axial
      resolution, the reduced excitation of out of focus fluorophores creates a very
      high signal to noise ratios and minimizes damaging effects of photobleaching.
      Being a widefield technique, TIRF also allows faster image acquisition than most
      scanning based confocal setups. At first glance, the low penetration depth of
      TIRF seems to be incompatible with imaging of bacterial and fungal cells, which
      are often surrounded by thick cell walls. On the contrary, we have found that the
      cell walls of yeast and bacterial cells actually improve the usability of TIRF
      and increase the range of observable structures. Many cellular processes can
      therefore be directly accessed by TIRF in small, single-cell microorganisms,
      which often offer powerful genetic manipulation techniques. This allows us to
      perform in vivo biochemistry experiments, where kinetics of protein interactions
      and activities can be directly assessed in living cells. We describe here the
      individual steps required to obtain high quality TIRF images for Saccharomyces
      cerevisiae or Bacillus subtilis cells. We point out various problems that can
      affect TIRF visualization of fluorescent probes in cells and illustrate the
      procedure with several application examples. Finally, we demonstrate how TIRF
      images can be further improved using established image restoration techniques.

PMID- 22588432
TI  - Ultrastructure, distribution, and transovarial transmission of symbiotic
      microorganisms in Nysius ericae and Nithecus jacobaeae (Heteroptera: Lygaeidae:
      Orsillinae).
AB  - The organization of the symbiotic system (i.e., distribution and ultrastructure
      of symbionts) and the mode of inheritance of symbionts in two species, Nysius
      ericae and Nithecus jacobaeae belonging to Heteroptera: Lygaeidae, are described.
      Like most hemipterans, Nysius ericae and Nithecus jacobaeae harbor obligate
      prokaryotic symbionts. The symbiotic bacteria are harbored in large, specialized
      cells termed bacteriocytes which are localized in the close vicinity of the
      ovaries as well as inside the ovaries. The ovaries are composed of seven
      ovarioles of the telotrophic type. Bacteriocytes occur in each ovariole in the
      basal part of tropharium termed the infection zone. The bacteriocytes form a ring
      surrounding the early previtellogenic oocytes. The cytoplasm of the bacteriocytes
      is tightly packed with large elongated bacteria. In the bacteriocytes of Nysius
      ericae, small, rod-shaped bacteria also occur. Both types of bacteria are
      transovarially transmitted from one generation to the next.

PMID- 22588433
TI  - Pediatrician knowledge, perception, and experience on child abuse and neglect in
      Saudi Arabia.
AB  - BACKGROUND AND OBJECTIVES: The objective of this study was to assess the
      knowledge, perception, and professional experience of pediatricians in Saudi
      Arabia regarding child abuse and neglect. DESIGN AND SETTING: Descriptive study
      during a one day pediatric conference held on King King Abdulaziz University
      Hospital , a tertiary care teaching hospital in western Saudi Arabia. PATIENTS
      AND METHODS: The study targeted 198 attendees who were invited from different
      healthcare sectors in the country. RESULTS: The overall knowledge of participants
      about some important aspects of child abuse and negligence was adequate, ranging
      between 82% and 91%. However, their knowledge about reporting cases of child
      abuse and neglect was quite deficient, ranging between 66% and 79%. As for
      professional experience about child abuse and negligence  it showed considerable
      variation between participants ranging between 43% and 82%, in which
      pediatricians who received their medical education in Saudi Arabia scored
      statistically significantly higher, while pediatricians who received their
      medical education in Western countries scored higher in all other aspects of the
      study. CONCLUSIONS: Currently, the knowledge and clinical experience on the
      subject of child abuse and neglect in Saudi Arabia is enough to adopt a
      comprehensive strategy for the prevention and interventions of child maltreatment
      at all levels. Pediatricians are expected to play a key role by leading and
      facilitating this process.

PMID- 22588434
TI  - Fasting among Muslim cancer patients during the holy month of Ramadan.
AB  - BACKGROUND AND OBJECTIVE: Muslims constitute more than 20% of the world's
      population and have a significant share of its cancer cases. Many Muslim cancer
      patients witness the fasting month of Ramadan but we do not know which
      individuals elect to fast. DESIGN AND SETTING: Cross-sectional study conducted
      among Muslim cancer patients at the National Cancer Institute (NCI), Egypt,
      during Ramadan, Hijri 1430 (the month of fasting) August-September 2009. SUBJECTS
      AND METHODS: One-hundred and two patients being treated at the NCI were
      interviewed. The most common diagnoses were breast cancer (31%), acute leukemia
      (24%), colorectal cancer (7%), non-Hodgkin lymphoma (5%), bladder cancer (4%),
      lung cancer (4%), and laryngeal cancer (4%). The two sexes were equally
      represented and so were metastatic and nonmetastatic diseases. The
      outpatient:inpatient ratio was 3:1. Treatments being received by these patients
      included chemotherapy, radiotherapy, hormonal therapy, and nonspecific therapy in
      42%, 31%, 10%, and 17%, respectively. Other concomitant diseases were present in
      22% of the patients. RESULTS: While 40% of patients did not fast at all during
      Ramadan, 36% and 24% were partial and complete fasters, respectively. Female
      patients, those with performance status (PS) 0 to 1, those whose disease was a
      nonmetastatic solid tumor, and those receiving non-intravenous chemotherapy as
      outpatients were more likely to be fasting than their corresponding counterparts.
      Being a female, having PS 0 to 1, and receiving treatment as an outpatient were
      the only factors that were significant on multivariate analysis. Only 46% of
      patients sought the treating oncologist advice on whether they could fast.
      CONCLUSIONS: Most cancer patients fast during Ramadan, but only half of them
      discuss the issue with their oncologists. We hope that our study stimulates more
      research on this topic.

PMID- 22588435
TI  - Prognostic significance of concomitant radiotherapy in newly diagnosed
      glioblastoma multiforme: a multivariate analysis of 116 patients.
AB  - BACKGROUND AND OBJECTIVES: Currently, radiotherapy with concomitant and adjuvant
      temozolomide has become the standard treatment for glioblastoma. The purpose of
      this study was to report our experience with radiation plus concomitant
      temozolomide in 116 patients with glioblastoma multiforme (GBM) and examine the
      value of different prognostic factors. DESIGN AND SETTING: Retrospective analysis
      of 116 patients with newly diagnosed GBM, who were treated at our department
      between January 1994 and March 2009. PATIENTS AND METHODS: Age, gender, Karnofsky
      performance scale (KPS) score, a preoperative history of seizures, extent of
      surgery, total radiotherapy dose, and use of concomitant and adjuvant
      temozolomide were evaluated in uni- and multivariate analyses. Survival was
      determined using the Kaplan-Meier method, and differences were compared using the
      log rank test. Cox regression analysis was conducted to identify the independent
      prognostic factors. RESULTS: The median overall survival time was 9 months, and
      the 1- and 2-year survival rates were 41.9% and 9.6%, respectively. The
      univariate analysis revealed that age, KPS score, presence of seizures, radiation
      doses, and use of concomitant and adjuvant temozolomide were significant
      prognostic factors. The multivariate analysis confirmed that the age, KPS score,
      presence of seizures, radiation doses, and use of concomitant and adjuvant
      temozolomide were independent, significant prognostic factors. CONCLUSIONS: The
      results of our analyses demonstrate that radiation with concomitant and adjuvant
      temozolomide yields encouraging outcomes in patients with GBM, validating the
      results published in research papers. In addition, age, KPS score, presence of
      seizures, and radiation doses were identified as prognostic factors.

PMID- 22588436
TI  - Expression of testis-specific genes, TEX101 and ODF4, in chronic myeloid leukemia
      and evaluation of TEX101 immunogenicity.
AB  - BACKGROUND AND OBJECTIVES: Cancer-testis (CT) antigens are a group of antigens
      with a restricted expression in normal tissues, except testis, and they have
      aberrant expression in different tumors. This pattern of expression has made them
      promising targets for immunotherapy and cancer detection. Our aim was to find new
      members of this group that might be useful as markers in the detection of cancer
      and immunotherapy. DESIGN AND SETTING: A descriptive study conducted in referral
      centers of Tehran University of Medical Science from January 2008 to January
      2009. PATIENTS AND METHODS: We analyzed the expression of two testis-specific
      genes named ODF4 (outer dense fiber of sperm tails 4) and TEX101 (testis
      expressed 101) in 20 chronic myeloid leukemia (CML) and 20 normal samples by
      reverse transcription-polymerase chain reaction and sequencing. Immunogenicity of
      TEX101 was evaluated by means of enzyme-linked immunosorbent assay. RESULTS:
      These two genes were expressed in 30% of CML patients but not in any of the
      healthy donors. Humoral response against TEX101 was not detected in any samples.
      CONCLUSIONS: TEX101 and ODF4 are CT genes useful for detection of CML. Unlike
      many CT genes, overexpression of TEX101 was not shown to induce immunologic
      responses in these samples. According to the previous studies, overexpression of
      TEX101 leads to suppression of cancer invasion and metastasis; thus, the
      induction of the expression of TEX101 in cancer by epigenetic mechanisms may be a
      treatment strategy.

PMID- 22588437
TI  - The effect of prostate tissue inflammation in benign prostatic hyperplasia on
      enhancer of zeste homolog 2 ribonucleic acid expression.
AB  - BACKGROUND AND OBJECTIVES: Enhancer of zeste homolog 2 (EZH2) has been recently
      found to regulate several genes involved in immunoresponse and autocrine
      inflammation network. The aim of the study was to quantitate EZH2 messenger
      ribonucleic acid (mRNA) expression, evaluate its relation to conditions of
      prostatitis associated with benign prostatic hyperplasia (BPH), and correlate it
      with the levels of the inflammatory marker interlukin 6 (IL-6). DESIGN AND
      SETTING: Cross-sectional study in Middle Eastern men with BPH and prostatitis or
      BPH only. PATIENTS AND METHODS: Transrectal ultrasound-guided prostate biopsies
      were collected from 106 patients suspected of having prostate cancer; however,
      the histology revealed BPH. Upon further pathological examination, 56 of these
      cases were identified as BPH with prostatitis and classified as: acute
      prostatitis (n=13); active chronic prostatitis (n=32); and, chronic inactive
      prostatitis (n=12). Serum IL-6 levels and EZH2 mRNA expression were measured and
      compared between patient groups. RESULTS: EZH2 mRNA was overexpressed in BPH with
      prostatitis patients compared to BPH only patients (P<.0001). BPH with active
      chronic prostatitis had higher EZH2 expression than BPH with acute or chronic
      inactive prostatitis compared to BPH only (P=.05 and .73, respectively). EZH2
      mRNA expression showed a negative correlation with IL-6 concentrations in BPH
      with prostatitis patients (rs=-0.31, P=.02). EZH2 overexpression was associated
      with an increased risk of having BPH with prostatitis (crude odds ratio 0.20, 95%
      CI 0.06-0.65, P=.0076). CONCLUSIONS: EZH2 mRNA expression correlates positively
      with prostatitis conditions associated with BPH and negatively with serum IL-6
      levels. This supports the possible involvement of EZH2 mRNA overexpression in the
      development of prostate inflammation, and its new regulatory role in suppressing
      the expression of some inflammatory network genes.

PMID- 22588438
TI  - Single-fraction gamma-60Co radiation induces apoptosis in cultured rat C6 cells.
AB  - BACKGROUND AND OBJECTIVES: Radiotherapy is frequently applied in the treatment of
      malignant gliomas, but it is unclear if radiotherapy exerts its effects via
      induction of apoptosis. The present study was designed to determine whether a
      single-fraction gamma-60Co radiation can induce apoptosis. DESIGN AND SETTING: In
      vitro cytological controlled study performed at a military medical university
      from October 2006 to June 2008. METHODS: C6 cells were treated with a single
      fraction of ?-60Co radiation at various doses (0, 4, 16, and 64 Gy). The 3-(4,5)
      dimethylthiazol-2)-2,5-diphenyl tetrazolium bromide (MTT) assay, apoptosis assays
      using Annexin V-fluorescein isothiocyanate /propidium iodide or Hoechst 33258
      staining, and the cell cycle assay were performed, and the expression of p53 and
      p21 proteins was evaluated. RESULTS: The C6 cell numbers in the 16 Gy and 64 Gy
      groups were much lower than in the control group at 48, 96, and 144 hours after
      irradiation. The irradiated cells underwent apoptosis in a dose-dependent manner.
      Irradiation also impacted cell cycle progression, arresting cells in the G1
      phase. The p53 protein expression was shown in both the nucleus and the cytoplasm
      of irradiated cells, whereas p53 was only expressed in the nucleus of control
      (untreated) cells. The p21 protein was expressed in irradiated cells but not in
      control cells. CONCLUSIONS: Single-fraction ?-60Co radiation inhibited C6 cell
      growth by inducing apoptosis and G1 arrest, which correlated with the up
      regulation of the p53-p21 pathway. The extent of apoptosis and G1 arrest was
      positively correlated with the dose of radiation. Better understanding of
      apoptosis induced by radiation therapy will help design optimal dosing schedules
      for radiation therapy, especially in combination with chemotherapy.

PMID- 22588439
TI  - Inflammatory bowel disease in Saudi Arabia: a hospital-based clinical study of
      312 patients.
AB  - BACKGROUND AND OBJECTIVES: The epidemiology, clinical characteristics, and
      natural course of inflammatory bowel disease (IBD) in Saudi Arabia are still
      largely unknown. Hence, we decided to conduct a large retrospective, cohort study
      to determine these features of the disease. DESIGN AND SETTING: Retrospective
      study conducted in a tertiary care hospital in Riyadh from January 1970 to
      December 2008. PATIENTS AND METHODS: We reviewed all the cases of IBD diagnosed
      and collected all data pertaining to patients with IBD. RESULTS: A total of 312
      patients with IBD were included for this analysis, including 197 (63%) patients
      with Crohn disease (CD) and 115 (37%) patients with ulcerative colitis (UC). The
      mean age (standard deviation) of patients with IBD was 25.5 (10.6) years; 152
      (48.7%) were males and 160 females. The referral rate in the past 10 years was
      72.1% compared with preceding 20 years, and 56% (n=178) of patients with IBD were
      from the central region of Saudi Arabia. The patients were followed up for a mean
      duration of 9.5 years; during their follow-up, 206 patients (66%) required
      hospital admission and 9 patients (2.9%)  with UC developed colon cancer. A total
      of 6 patients died during the follow-up. Fifty-three percent (n=104) of the
      patients with CD underwent surgeries as part of their treatment, whereas only 20%
      (n=23) of the patients with UC underwent colectomy. CONCLUSIONS: The incidence of
      IBD has been gradually increasing in Saudi Arabia over the years. Clinical
      features and morbidity in patients are not different from patients with IBD seen
      in the West.

PMID- 22588440
TI  - Profile of mycosis fungoides in 43 Saudi patients.
AB  - BACKGROUND AND OBJECTIVES: Mycosis fungoides (MF) is a rare disease; and to our
      knowledge, there are no reports on its profile in Arabs. The objective of this
      study was to preliminarily analyze the clinical characteristics of MF patients
      seen in our institution. DESIGN AND SETTING: Retrospective review of 140 patients
      with pathologic or clinical diagnosis or differential diagnosis of MF for the
      period 2000-2006. PATIENTS AND METHODS: Pathology reports with diagnosis or
      differential diagnosis of MF were retrieved and suspected cases were identified
      and reviewed. For pathologically confirmed cases, sociodemographic, clinical,
      laboratory, and radiological details were collected. Details of staging,
      treatment modalities, and disease status at the last follow-up were retrieved.
      RESULTS: A total of 43 pathologically confirmed MF patients (skin phototypes IV
      and V) with a mean age at diagnosis of 33.5 years were reviewed. This comprised
      29 males (M:F ratio, 2:1), and the majority (86%) of patients had early-stage (I
      and II) MF. Twenty-one (48.8%) patients had classic MF; 18 (41.8%), hypopigmented
      MF; and 4 (9.3%), other variants. The male-to-female ratio was higher in the
      hypopigmented (3.5:1) than in the classic variant (1.6:1). The mean age at
      diagnosis was lower in the hypopigmented compared to the classic variant (25
      versus 38.8 years, P=.019). The mean duration of follow-up was 27.6 months
      (range, 1-98 months). At the final assessment, 4 (9.5%) patients recovered;
      whereas 35 (83.3%) had MF skin disease; 1 had (2.4%) extracutaneous disease; and
      2 (4.8%) died of MF. CONCLUSIONS: MF tends to affect younger Saudi patients. The
      hypopigmented variant constitutes a significant proportion of MF cases,
      especially in younger patients.

PMID- 22588442
TI  - Song listening does not affect pattern reversal visual evoked potentials.
AB  - BACKGROUND AND OBJECTIVE: The pattern reversal visual evoked response has been
      defined as a reproducible cortical response upon stimulation of the eyes. This
      response depends on the intensity of the light stimulus and its distance from the
      eyes and is not affected by simultaneous tactile or auditory stimulation.
      However, in some patients we observe different P100 latencies, at different
      intervals of testing, without lesions of the optic tracts. The purpose of this
      study was to evaluate whether a loud meaningful acoustic noise, simulated by song
      listening, during the testing of the visual evoked response, could alter the
      latency or amplitude of the cortical potentials. DESIGN AND SETTING: The study
      was performed in the Clinical Neurophysiology Laboratory of the Medical Center by
      one technician trained to perform visual evoked potential analysis. SUBJECTS AND
      METHODS: We performed pattern reversal visual evoked potentials on 40 eyes of
      normal individuals at rest and during auditory stimulation with loud meaningful
      acoustic noise in the form of songs familiar to the subject. We compared the
      latencies and amplitudes of the P100 wave during these two test conditions.
      RESULTS: The latencies and amplitudes of the P100 waves evoked upon stimulation
      of the eyes of the subjects did not differ statistically during the test at rest
      and upon stimulation with songs simulating loud acoustic noise. CONCLUSIONS: We
      conclude that loud song listening has no effect on the pattern reversal visual
      evoked potential latency or amplitude. Thus, it seems likely that the results are
      independent of environmental acoustic noise.

PMID- 22588441
TI  - Epidemiological, clinical, and biochemical characteristics of Saudi patients with
      nonalcoholic fatty liver disease: a hospital-based study.
AB  - BACKGROUND: The estimated prevalence of nonalcoholic fatty liver disease (NAFLD)
      in Saudi Arabia is 7% to 10%. Despite the high prevalence of risk factors
      including diabetes, obesity, and hyperlipidemia, no recent epidemiological
      studies have measured the disease burden. We aimed to determine the
      characteristics of Saudi NAFLD patients attending a university hospital, and
      study factors affecting alanine aminotransferase (ALT) levels. DESIGN AND
      SETTING: A prospective study among patients referred for ultrasonography in King
      Khalid University Hospital in Riyadh, Saudi Arabia from February to May 2009.
      PATIENTS AND METHODS: NAFLD was defined as an appearance of fatty liver on
      routine abdominal ultrasound in the absence of coexisting liver disease and
      alcohol consumption. Patients were classified into normal and high ALT (ALT >60
      U/L) level groups for analysis. RESULTS: The prevalence of NAFLD was 16.6%
      (218/1312). Patients with normal ALT had the mean (SD) age of 45.9 (10.6) years
      and the mean body mass index of 34.5 (7.9) kg/m2. Forty percent of the 151
      patients with normal ALT had diabetes, 66.2% were obese, and 29.1% had
      hypertension. Forty-three patients (23%) had high ALT levels. These patients had
      significantly lower age (P=.003) and fasting blood sugar (P=.03) than the normal
      ALT group. Non-diabetic patients (odds ratio 0.30, 95% CI 0.1-0.8), men (female
      OR 0.23, 95% CI 0.1-0.5), lower cholesterol (P=.001), high-density lipoprotein
      (P=.006), and low-density lipoprotein (P=.008) levels were more likely to be
      observed among patients with high ALT levels. In a multivariate analysis, younger
      age (OR 0.96, 95% CI 0.93-0.99), being male (OR 0.23, 95% CI 0.09-0.57), and a
      lower cholesterol level (OR 0.55, 95% CI 0.37-0.82) were significant predictors
      of high ALT levels. CONCLUSION: Based on the high prevalence of obesity and
      diabetes, the prevalence of NAFLD will continue to be high, unless awareness is
      inculcated among the local population.

PMID- 22588443
TI  - The current lymphoma classification: new concepts and practical applications
      triumphs and woes.
AB  - The World Health Organization (WHO) classification of lymphomas updated in 2008
      represents an international consensus for diagnosis of lymphoid neoplasms based
      on the recognition of distinct disease entities by applying a constellation of
      clinical and laboratory features. The 2008 classification has refined and
      clarified the definitions of well-recognized diseases, identified new entities
      and variants, and incorporated emerging concepts in the understanding of lymphoid
      neoplasms. Rather than being a theoretical scheme this classification has used
      data from published literature. Recent knowledge of molecular pathways has led to
      identification and development of new diagnostic tools, like gene expression
      profiling, which could complement existing technologies.  However, some questions
      remain unresolved, such as the extent to which specific genetic or molecular
      alterations define certain tumors. In general, practical considerations and
      economics preclude a heavily molecular and genetic approach. The significance of
      early or precursor lesions and the identification of certain lymphoid neoplasms
      is less clear at present, but understanding is evolving. The borderline
      categories having overlapping features with large B-cell lymphomas, as well as
      some of the provisional entities, are subject to debate and lack consensus in
      management. Lastly, the sheer number of entities may be overwhelming, especially,
      for the diagnosing pathologist, who do not see enough of these on a regular
      basis.

PMID- 22588444
TI  - Tumor lysis syndrome during radiotherapy for prostate cancer with bone and bone
      marrow metastases without visceral metastasis.
AB  - A 60-year-old male patient presented to our clinic with metastatic (bone and bone
      marrow) prostate cancer. Radiotherapy (RT) with a total of 30 Gy was planned in
      10 fractions for the painful left shoulder region. On the 6th day of RT, urinary
      output decreased suddenly and dyspnea developed. Laboratory findings suggested
      tumor lysis syndrome (TLS). The patient, who showed improvement in overall status
      and had no requirement for hemodialysis up to this time, developed sudden
      impairment in overall status, dyspnea, and hypotension on the 11th day of follow
      up. Thirty minutes after the development of these symptoms, the patient had a
      cardiopulmonary arrest and died. At the time of writing this was the fourth case
      of TLS during RT for solid tumors in adults, the first case of TLS during RT for
      prostate cancer and the fifth among total cases of prostate cancer in published
      reports.

PMID- 22588445
TI  - A fatal case of cutaneous adverse drug-induced toxic epidermal necrolysis
      associated with severe rhabdomyolysis.
AB  - Toxic epidermal necrolysis represents an immunologic reaction to a foreign
      antigen and is most often caused by drugs. Atorvastatin, a blood cholesterol
      lowering agent, is a recognized cause of rhabdomyolysis; while naproxen, a widely
      used nonsteroidal anti-inflammatory drug, is a known cause of photo-induced skin
      lesions. We report the first fatal case of drug-induced toxic epidermal
      necrolysis associated with severe muscle necrosis due to the use of a
      nonsteroidal anti-inflammatory drug and a statin with very high levels of
      creatine phosphokinase leading to acute kidney injury, disseminated intravascular
      coagulation, and complete skin necrosis leading to death.

PMID- 22588446
TI  - First case report of chronic pulmonary lung disease caused by Mycobacterium
      abscessus in two immunocompetent patients in Saudi Arabia.
AB  - Mycobacterium abscessus is a rapidly growing non-tuberculous mycobacterium that
      is a common water contaminant, and an exclusive opportunistic pathogen in
      immunosuppressed patients; however, it occasionally causes lung infections in
      immunocompetent persons as well. We report two cases of chronic pulmonary
      infection caused by M abscessus in two young migrant workers; they were
      nonreactive to HIV antigen, without any history of pulmonary disorders and no
      evidence of any immunocompromized status. Both were initially suspected as having
      pulmonary tuberculosis, and antituberculosis drugs were administered. The
      preliminary culture found the isolate as a rapidly growing nontuberculous
      mycobacteria and later by advanced molecular genotyping of the isolates revealed
      it as M abscessus. The patients were treated with multiple drugs including
      clarithromycin. The symptoms resolved slowly, the smears and culture became
      negative, and they recovered completely. This is the first case of its type to be
      reported from Saudi Arabia.

PMID- 22588447
TI  - Ricin poisoning causing death after ingestion of herbal medicine.
AB  - Ricin intoxication is a fatal and an uncommon medical condition. We report a case
      of ricin poisoning in a 42-year-old Saudi male patient who ingested a herbal
      medicine mixture containing ricin bean powder, after which he presented with
      gastrointestinal symptoms followed by gastrointestinal bleeding and hypotension.
      The patient then passed into a state of shock with respiratory failure followed
      by cardiac arrest and death. Public health awareness of self-prescribed herbal
      medications is necessary.

PMID- 22588448
TI  - Diffuse skin hyperpigmentation in CD30+ lymphoproliferation.
AB  - CD30+ T-cell lymphoproliferative disorders (LD) comprise two main groups of
      diseases: CD30+ LD of the skin and systemic anaplastic large cell lymphoma
      (ALCL). The main feature of these disorders is the expression of CD30. We present
      a patient with an unusual clinical presentation of CD30+ lymphoproliferative
      disease in a 54-year old Caucasian male who presented with generalized
      lymphadenopathy and pronounced skin hyperpigmentation. In the lymph nodes and
      skin, CD30+ lymphoproliferation (ALCL) was diagnosed. The Prussian blue staining
      identified that the pigment responsible for the skin color was hemosiderin.
      Chemotherapy was started but the patient's condition progressively worsened and
      he died a week after the first cycle. The complete color transformation of the
      entire skin due to hemosiderin accumulation is, to the best of our knowledge, the
      first reported observation in a CD30+ lymphoproliferation/ALCL patient. We
      speculate that hemosiderin-loaded macrophages resulted from the paraneoplastic
      process by some still unknown mechanism.

PMID- 22588449
TI  - Skull metastasis from hepatocellular carcinoma with hepatitis C.

PMID- 22588450
TI  - Fever of unknown origin, anemia and thrombocytosis as early symptoms and signs of
      a late-onset polymialgia rheumatica: a diagnostic challenge.

PMID- 22588451
TI  - RE: Seatbelt compliance and mortality in the Gulf Cooperation Council countries
      in comparison with other high-income countries.

PMID- 22588453
TI  - Unpredictable dance of worms.

PMID- 22588454
TI  - The neurosciences in Averroes principles of medicine.
AB  - One of the fundamental advances of the transition of the Middle Ages to the
      Renaissance was the rediscovery of the Greek philosophers. Among the greatest
      representatives of this epoch we find the Cordovan doctor and philosopher
      Averroes (Ibn Rushd) who, with his commentaries on the works of Aristotle,
      brought a new philosophical vision to Western Europe. His contribution to
      medicine has been overshadowed to some extent by this great work of philosophy.
      Our intention is to evaluate, in the context of the neurosciences, the vision of
      health and sickness that he left us in his book "The Book of the Principles of
      Medicine. The organisation of the Kulliyat is based on Aristotelian concepts.
      Averroes regarded the nervous system not as single entity but rather as a complex
      of various elements. The anatomy of the nervous system is studied in two parts:
      the encephalus and the periphery. Both the encephalic nervous system and the
      sensory organs are regarded as heterogeneous organs. Averroes structures the
      anatomical order without taking into account the local movements of the living
      body. The mission of the senses is to maintain contact between external reality
      and the structure of the organism. This requires an external process, a point of
      union and an internal process. The ultimate goal is the preservation of health in
      a balanced disposition and the cure of disease in the organism in disequilibrium.

PMID- 22588456
TI  - The relation between age, sex, comorbidity, and pharmacotherapy and the risk of
      syncope: a Danish nationwide study.
AB  - AIMS: Syncope is a common cause for hospitalization and may be related to
      comorbidity and concurrent medication. The objective of this study was to
      determine the incidence, comorbidity, and pharmacotherapy in a nationwide cohort
      of patients hospitalized with syncope. METHODS AND RESULTS: An observational
      study including patients with the diagnosis of syncope identified from the Danish
      National Patient Register in the period 1997-2009. All patients were matched on
      sex and age with five controls from the Danish population. We estimated the
      incidence of syncope and the association with comorbidities and pharmacotherapy
      by conditional logistic regression analyses. We identified 127 508 patients with
      a first-time diagnosis of syncope [median age 65 years (interquartile range 49
      81), 52.6% female]. The age distribution of the patients showed three peaks
      around 20, 60, and 80 years of age with the third peak occurring 5-7 years
      earlier in males. Cardiovascular disease and cardiovascular drug therapy was
      present in 28 and 48% of the patients, respectively. We found significant
      association between cardiovascular disease and the risk of admission for syncope
      increasing with younger age; age 0-29 years [odds ratio (OR) = 5.8, confidence
      interval (CI): 5.2-6.4), age 30-49 (OR = 4.4, CI: 4.2-4.6), age 50-79 (OR = 2.9,
      CI: 2.8-3.0), and age above 80 (OR = 2.0, CI: 1.9-2.0). Cardiovascular
      pharmacotherapy associated with age and risk of syncope was similar. CONCLUSION:
      In a nationwide cohort of patients hospitalized for first syncope we found
      significant association between cardiovascular comorbidity and pharmacotherapy
      and the risk of syncope. The occurrence of syncope displayed an age distribution
      with important gender-specific differences and higher incidence rates than
      previously reported.

PMID- 22588455
TI  - Update on diabetes diagnosis: a historical review of the dilemma of the
      diagnostic utility of glycohemoglobin A1c and a proposal for a combined glucose
      A1c diagnostic method.
AB  - The role of glycohemoglobin A1c (A1c) for the diagnosis of diabetes has been
      debated for over three decades. Recently, the American Diabetes Association (ADA)
      has recommended adding A1c as an additional criterion for diabetes diagnosis. In
      view of the continued debate about the diagnostic utility of A1c, and in view of
      the unabated burden of undiagnosed diabetes, the search for alternative
      diagnostic methods is discussed. A historical literature review is provided, in
      view of the new ADA diagnostic guidelines, and a proposal is provided for
      combining A1c and a glucose measurement as a diagnostic alternative/adjunct to
      the use of a single criterion. This proposal is based on the non-overlapping of
      the advantages and disadvantages of these individual tests. The cost
      effectiveness of this method remains to be tested.

PMID- 22588457
TI  - Positron emission tomography in a complex case of cardiac device-related
      infection.

PMID- 22588458
TI  - Dormant conduction revealed by adenosine to guide electrical isolation of the
      superior vena cava.

PMID- 22588459
TI  - Use of intravenous immunoglobulin compared with standard therapy is associated
      with improved clinical outcomes in children with acute encephalitis syndrome
      complicated by myocarditis.
AB  - Although an autoimmune mechanism has been postulated for acute encephalitis
      syndrome (AES) complicated by myocarditis, immunomodulatory treatment strategies
      are still under investigation. To study the role of intravenous immunoglobulin
      (IVIG) in AES complicated by myocarditis in children age 2-12 years. This
      nonrandomized study was conducted in a tertiary care teaching hospital from July
      2008 to January 2010. A total of 83 consecutive children with AES complicated by
      myocarditis were enrolled. Diagnosis of myocarditis was based on clinical,
      electrocardiogram, and echocardiogram findings. Patients were allocated to the
      two groups based on the days of the week: Those presenting on Monday and Friday
      were allocated to IVIG treatment (group I), and those presenting on the other
      days of the week to standard care (group II). Group I (n = 26) patients received
      IVIG at a dose of 400 mg/kg/day for 5 days in addition to standard care. All
      baseline and outcome data were recorded prospectively in a prestructured
      performa. The primary outcomes were mortality and improvement of left-ventricular
      dysfunction. A total of 83 children were studied: 26 in group I and 57 in group
      II. The mean (SD) age of the enrolled children was 4.6 years (3.1). The baseline
      characteristics were comparable between the two groups. A viral etiology could be
      established in 14 children, with the 2 most common agents isolated being Coxackie
      virus and enterovirus. Mortality was lower in the IVIG group [n = 1 (3.8 %)]
      patients compared with the standard care group [n = 13 (22.8 %)] with a relative
      risk of 0.17 (95 % CI = 0.02, 1.22). The difference in mortality reached
      borderline significance (p = 0.05). At discharge, mean (SD) ejection fraction
      improved from 32.8 % (6.31 %) to 49.5 % (9.04 %) in group I patients, which was
      significantly greater than that of group II (p = 0.001). Use of IVIG seemed to
      have a beneficial effect in terms of improved clinical outcomes in children with
      AES complicated by myocarditis. Our findings need further validation before IVIG
      can be incorporated into the treatment protocol of these children.

PMID- 22588460
TI  - Warfarin anticoagulation after congenital heart surgery at a large children's
      hospital.
AB  - Management of warfarin in pediatric patients remains a clinical challenge.
      Warfarin may be administered after congenital heart surgery, and the risks of
      morbidity can be high. Currently, no data exist to describe the initiation of
      warfarin and the risk factors for morbidity in post-congenital heart surgery
      patients. This study aimed to characterize the time required to reach
      anticoagulation for patients administered warfarin therapy after cardiac surgery
      and to identify and characterize the risk factors for supratherapeutic
      anticoagulation and adverse events after warfarin initiation. This retrospective
      study reviewed all patients between 2006 and 2011 who received warfarin
      anticoagulation after cardiac surgery at our institution. Factors associated with
      a prolonged time required to reach an international normalized ratio (INR) of 2
      and factors related to supratherapeutic anticoagulation (INR >= 4) were
      identified. The inclusion criteria were met by 59 patients. The median time
      required to reach an INR of at least 2 after initiation of warfarin was 2 days
      (interquartile range (IQR), 2-4). The only groups that required a significantly
      longer time to reach an INR of 2 were those with a postoperative delay in
      initiation of warfarin and those receiving heparin anticoagulation before and
      during warfarin initiation. Nine patients experienced an INR of 4 or more.
      However, no thrombotic events occurred, and significant bleeding was uncommon. In
      the largest reported group of patients undergoing anticoagulation after cardiac
      surgery, warfarin was well tolerated across all age groups. The median time
      required to reach an INR of 2 after loading with warfarin was 2 days, and adverse
      events were uncommon.

PMID- 22588461
TI  - Angiotensin receptor-associated proteins: local modulators of the renin
      angiotensin system.
AB  - The activity of the renin-angiotensin system crucially depends on the rate of
      renal renin secretion. Changes in renin secretion result in fluctuations of
      angiotensin II concentrations in the circulation and subsequently in the
      activation of angiotensin receptors in all accessible target organs.
      Consequently, various mechanisms have evolved to regulate the local sensitivity
      to angiotensin II. In this review, an overview of angiotensin II receptor
      associated proteins is addressed. These proteins regulate the local sensitivity
      of receptor-expressing cells by modulating the receptor surface expression and
      the receptor sensitivity. A hypothesis will be discussed that integrates the
      existence of various angiotensin receptor-associated proteins into an overall
      functional model.

PMID- 22588462
TI  - Physiologically based biokinetic (PBBK) modeling of safrole bioactivation and
      detoxification in humans as compared with rats.
AB  - A physiologically based biokinetic (PBBK) model for the  alkenylbenzene safrole
      in humans was developed based on in vitro- and in silico-derived kinetic
      parameters. With the model obtained, the time- and dose-dependent formation of
      the proximate and ultimate carcinogenic metabolites, 1-hydroxysafrole and 1
      sulfooxysafrole in human liver were estimated and compared with previously
      predicted levels of these metabolites in rat liver. In addition, Monte Carlo
      simulations were performed to predict interindividual variation in the formation
      of these metabolites in the overall population. For the evaluation of the model
      performance, a comparison was made between the predicted total amount of urinary
      metabolites of safrole and the reported total levels of metabolites in the urine
      of humans exposed to safrole, which adequately matched. The model results
      revealed no dose-dependent shifts in safrole metabolism and no relative increase
      in bioactivation at dose levels up to 100mg/kg body weight/day. Species
      differences were mainly observed in the detoxification pathways of 1
      hydroxysafrole, with the formation of 1-oxosafrole being a main detoxification
      pathway of 1-hydroxysafrole in humans but a minor pathway in rats, and
      glucuronidation of 1-hydroxysafrole being less important in humans than in rats.
      The formation of 1-sulfooxysafrole was predicted to vary 4- to 17-fold in the
      population (fold difference between the 95th and median, and 95th and 5th
      percentile, respectively), with the median being three to five times higher in
      human than in rat liver. Comparison of the PBBK results for safrole with those
      previously obtained for the related alkenylbenzenes estragole and methyleugenol
      revealed that differences in 1-sulfooxy metabolite formation are limited, being
      only twofold to fivefold.

PMID- 22588463
TI  - Meta-analysis of nanoparticulate paclitaxel delivery system pharmacokinetics and
      model prediction of associated neutropenia.
AB  - PURPOSE: Nanoparticulate paclitaxel carriers have entered clinical evaluation as
      alternatives to the Cremophor-based standard Taxol((r)) (Cre-pac). Their
      pharmacokinetics (PK) is complex, and factors influencing their pharmacodynamics
      (PD) are poorly understood. We aimed to develop a unified quantitative model for
      4 paclitaxel carriers that captures systems-level PK, predicts micro-scale PK
      processes, and permits correlations between carrier properties and observed PD.
      METHODS: Data consisting of 54 PK profiles and 574 observations were extracted
      from 20 clinical studies investigating Cre-pac, albumin-(A-pac), liposome-(L
      pac), and tocopherol-(T-pac) nanocarriers. A population-PK approach was used for
      data analysis. All datasets were simultaneously fitted to produce a unified
      model. Model-based simulations explored relationships between predicted PK and
      myelosuppression for each formulation. RESULTS: The final model employed
      nonlinear drug-binding mechanisms to describe Cre-pac and a delayed-release model
      for A-pac, L-pac, and T-pac. Estimated drug-release rate constants (h(-1)): Cre
      pac (5.19), L-pac (1.26), A-pac (0.72), T-pac (0.74). Simulations of equivalent
      dosing schemes ranked neutropenia severity (highest to lowest): T-pac~Cre-pac>L
      pac~A-pac and predicted remarkably well the clinically-observed relationships
      between neutropenia and free drug exposure relative to a threshold concentration.
      CONCLUSIONS: Paclitaxel disposition was well-described for all formulations. The
      derived model predicts toxicodynamics of diverse paclitaxel carriers.

PMID- 22588464
TI  - Spike suppression in a local cortical circuit induced by transcranial magnetic
      stimulation.
AB  - Transcranial magnetic stimulation (TMS) noninvasively interferes with human
      cortical function, and is widely used as an effective technique for probing
      causal links between neural activity and cognitive function. However, the
      physiological mechanisms underlying TMS-induced effects on neural activity remain
      unclear. We examined the mechanism by which TMS disrupts neural activity in a
      local circuit in early visual cortex using a computational model consisting of
      conductance-based spiking neurons with excitatory and inhibitory synaptic
      connections. We found that single-pulse TMS suppressed spiking activity in a
      local circuit model, disrupting the population response. Spike suppression was
      observed when TMS was applied to the local circuit within a limited time window
      after the local circuit received sensory afferent input, as observed in
      experiments investigating suppression of visual perception with TMS targeting
      early visual cortex. Quantitative analyses revealed that the magnitude of
      suppression was significantly larger for synaptically-connected neurons than for
      isolated individual neurons, suggesting that intracortical inhibitory synaptic
      coupling also plays an important role in TMS-induced suppression. A conventional
      local circuit model of early visual cortex explained only the early period of
      visual suppression observed in experiments. However, models either involving
      strong recurrent excitatory synaptic connections or sustained excitatory input
      were able to reproduce the late period of visual suppression. These results
      suggest that TMS targeting early visual cortex disrupts functionally distinct
      neural signals, possibly corresponding to feedforward and recurrent information
      processing, by imposing inhibitory effects through intracortical inhibitory
      synaptic connections.

PMID- 22588465
TI  - What impact will reducing concurrency have on decreasing the incidence of HIV in
      heterosexual populations?

PMID- 22588466
TI  - Context, networks, and sexually transmitted infections:  a study of sex ratios
      and male incarceration.

PMID- 22588467
TI  - Dosimetric comparison of free-breathing and deep inspiration breath-hold
      radiotherapy for lung cancer.
AB  - PURPOSE: The goal of this work was to evaluate the potential benefit of deep
      inspiration breath-hold (DIBH) compared to free breathing (FB) radiotherapy in a
      homogeneous population of patients with lung cancer. METHODS AND MATERIALS: A
      total of 25 patients with non-small cell lung cancer treated by DIBH underwent an
      additional FB CT scan. The DIBH and FB treatment plans were compared. Target
      volume was compared using coverage, homogeneity, and conformal indices. Organs at
      risk were compared using V(5), V(13), V(20), V(25), V(37), mean dose (D(mean))
      for lungs, V(40) and D(mean) for the heart, V(50), D(mean) and maximum dose
      (D(max)) for the esophagus, and using biological indices, i.e., the equivalent
      uniform dose (EUD) and the normal tissue complication probability (NTCP).
      RESULTS: Median age was 62 years. Prescribed total dose was 66 Gy. Conformity
      index was improved with DIBH (0.67 vs. 0.58, p = 0.046) but coverage and
      homogeneity indices were not significantly different. Lung dosimetric parameters
      were improved using DIBH: D(mean) (13 vs. 15 Gy, p = 10(-4)), V(5) (43 vs. 51%, p
      = 6.10(-5)), V(13) (31 vs. 38%, p = 2.10(-3)), V(20) (25 vs. 31%, p = 0.01),
      V(25) (22% vs. 27%, p = 0.01) and V(37) (12 vs. 16%, p = 0.03), EUD (8.2 vs. 9.9
      Gy, p = 3.10(-4)), and NTCP (1.9 vs. 4.8%, p = 10(-3)). For the heart, D(mean)
      (14 vs. 17 Gy, p = 0.003), V(40) (12 vs. 17%, p = 0.004), and EUD (19 vs. 22 Gy,
      p = 6.10(-4)) were reduced with DIBH, whereas V(30) and NTCP were similar. DIBH
      improved the D(mean) (28 vs. 30 Gy, p = 0.007) and V(50) (25 vs. 30%, p = 0.003)
      for the esophagus, while EUD, NTCP, and D(max) were not altered. CONCLUSION: DIBH
      improves the target conformity index and heart and lung dosimetry in lung cancer
      patients treated with radiotherapy. The clinical implications of these findings
      should be confirmed.

PMID- 22588468
TI  - Integrating bioinformatics and clinicopathological research of gastrointestinal
      stromal tumors: identification of aurora kinase A as a poor risk marker.
AB  - BACKGROUND: For completely resected primary gastrointestinal stromal tumors
      (GISTs), mitotic rate, tumor size, and tumor location are important risk factors
      for recurrence. However, molecular markers for recurrence are still lacking.
      METHODS: We reanalyzed GIST gene expression profile GSE8167 available from the
      Gene Expression Omnibus (GEO) and confirmed the prognostic influence of one
      selected gene, aurora kinase A (AURKA), in another cohort of 142 patients using
      immunohistochemistry (IHC). RESULTS: Thirty-two cases in GSE8167 were classified
      into two risk groups with distinct recurrence-free survival (RFS) and expression
      profiles using modified criteria of Miettinen et al. from the Armed Forces
      Institute of Pathology (AFIP-Miettinen). AURKA was among the 19 genes common to
      the top 50 features of the high-risk phenotype and a 67-gene signature called the
      complexity index in sarcomas. AURKA was significantly overexpressed in the high
      risk group, and patients with high AURKA expression had significantly worse RFS
      than those with low expression. In the IHC-validated cohort, AURKA expression was
      significantly higher in nongastric tumors than in gastric tumors and was
      significantly correlated with AFIP-Miettinen risk group. Univariate analysis
      showed that RFS was significantly influenced by tumor size, mitotic count, AFIP
      Miettinen risk group classification, and AURKA expression. However, only tumor
      size (P = 0.017), mitotic count (P = 0.007), and AURKA expression (P = 0.039)
      were identified as independent unfavorable prognostic factors for RFS in
      multivariate analysis. CONCLUSIONS: By integrating bioinformatics and
      clinicopathological studies, AURKA was identified as a marker for high-risk GIST.

PMID- 22588469
TI  - The beta2-adrenergic receptor is a potential prognostic biomarker for human
      hepatocellular carcinoma after curative resection.
AB  - BACKGROUND: The beta2-adrenergic receptor (Beta2-AR) is overexpressed and highly
      associated with poor prognosis in many malignancies. Nevertheless, the role of
      Beta2-AR in hepatocellular carcinoma (HCC) has not been thoroughly elucidated.
      The aim of this study is to investigate the expression of Beta2-AR and its
      clinicopathological/prognostic value in HCC patients after curative resection.
      MATERIALS AND METHODS: Semiquantitative reverse transcription PCR (RT-PCR) and
      real-time quantitative PCR (qPCR) were used to measure Beta2-AR RNA expression in
      60 pairs of HCC tumors and matched nontumorous tissues. Beta2-AR expression was
      detected in HCC cell lines by Western blot analysis. Furthermore, we investigated
      Beta2-AR expression in correlation with the clinicopathological features and
      analyzed the potential prognostic significance of Beta2-AR in 192 HCC patients by
      immunohistochemistry (IHC). RESULTS: Upregulation of Beta2-AR mRNA was
      significantly higher in HCC tumor tissues than in their paired nontumorous liver
      specimens. The expression of Beta2-AR protein was detected in five HCC cell
      lines. Positive Beta2-AR protein expression was significantly associated with a
      high alpha-fetoprotein (AFP) level (P = 0.001), large tumor size (P < 0.001),
      tumor encapsulation (P = 0.002), vascular invasion (P = 0.004), microsatellite
      formation (P = 0.002), and poor differentiation (P < 0.001). In univariate and
      multivariate analyses, Beta2-AR was an excellent predictive factor for both
      recurrence-free survival and overall survival (OS). Beta2-AR expression status
      was associated with poor prognosis independent of AFP, tumor-node-metastasis
      stage and Edmondson stage. CONCLUSIONS: The Beta2-AR is a potential prognostic
      biomarker for survival and tumor recurrence in HCC patients after curative
      resection.

PMID- 22588470
TI  - Short-term outcomes of ablation therapy for hepatic tumors: evidence from the
      2006-2009 nationwide inpatient sample.
AB  - BACKGROUND: Radiofrequency ablation (RFA) for the treatment of hepatic tumors has
      been increasingly used across the United States. Whether treatment-related
      morbidity has remained low with broader adoption is unclear. We conducted this
      study to describe in-hospital morbidity associated with RFA for hepatic tumors
      and to identify predictors of adverse events in a nationally representative
      database. METHODS: Using the 2006-2009 Nationwide Inpatient Sample, we evaluated
      all patients aged >=40 years who underwent an elective RFA for primary or
      metastatic liver tumors (N = 1298). Outcomes included in-hospital procedure
      specific and postoperative complications. Multivariable logistic regression
      analyses were performed to identify patient and facility predictors of
      complications. RESULTS: Most patients underwent a percutaneous (39.9 %) or
      laparoscopic (22.0 %) procedure for metastatic liver tumors (57.5 %). Procedure
      specific complications were frequent (18.2 %), with transfusion requirements
      (10.7 %), intraoperative bleeding (4.3 %), and hepatic failure (2.8 %) being the
      most common. Arrhythmias [adjusted odds ratio (AOR) = 1.93 (1.23-3.04)],
      coagulopathy [AOR = 4.65 (2.95-7.34)], and an open surgical approach [AOR = 2.77
      (1.75-4.36)] were associated with an increased likelihood of procedure-specific
      complications, whereas hospital RFA volume >=16/year was associated with a
      reduced likelihood [AOR = 0.59 (0.38-0.91)]. Postoperative complications were
      also common (12.0 %), with arrhythmias, heart failure, coagulopathy, and open
      surgical approach acting as significant predictors. CONCLUSIONS: In-hospital
      morbidity is common after RFA for hepatic tumors. While several patient factors
      are associated with more frequent procedure-specific complications, treatment at
      hospitals with an annual volume >=16 cases/year was associated with a 41 %
      reduction in the odds of procedure-specific complications.

PMID- 22588471
TI  - Surgery for distant metastatic melanoma improves survival.

PMID- 22588473
TI  - Broadening the signal specificity of prokaryotic promoters by modifying cis
      regulatory elements associated with a single transcription factor.
AB  - In this report, we experimentally demonstrate that improving the cis-regulatory
      region of a target promoter can significantly enhance the response to an
      otherwise poor inducer. The transcriptional factor (TF) BenR of Pseudomonas
      putida KT2440 is a member of the AraC/XylS family that activates the Pb promoter
      in response to benzoate. This TF can also trigger Pb activity in response to 3
      methylbenzoate (3MBz), but with lower efficiency. Unlike other family members,
      BenR appears to recognize one operator partially overlapping the -35 promoter
      region and which is followed by an upstream DNA sequence that lacks an essential
      motif for TF binding. By generating a promoter variant composed of two complete
      operator sequences, we observed an enhancement in the sensitivity of Pb to the
      two inducers. This effect was more pronounced in the case of 3MBz, for which the
      transcriptional response was approximately 4-5 times higher with the variant than
      with the wild type promoter. By comparing the responses of the promoters to
      different concentrations of the inducers, we observed that the modification of
      the BenR binding region changes the inherent logic of Pb from an amplifier-like
      behaviour, in which benzoate acts as the sole input, towards OR-gate behaviour,
      in which 3MBz acts as a second input. Using a mathematical model, we deduced that
      the second binding site engineered in the Pb promoter enhances the activity of
      BenR that is bound to the natural operator region, increasing the inducing
      sensitivity. This work demonstrates how the promiscuity or specificity of inducer
      recognition can be tuned in a regulatory network without TF mutation and suggests
      new strategies for the engineering of logic operations in living systems.

PMID- 22588472
TI  - Therapeutic lymph node dissection in melanoma: different prognosis for different
      macrometastasis sites?
AB  - BACKGROUND: The prognostic significance of primary tumor location, especially the
      poor prognosis for melanomas in the scalp and neck region, is well established.
      However, the prognosis for different sites of nodal macrometastasis has never
      been studied. This study investigated the prognostic value of the location of
      macrometastasis in terms of recurrence and survival rates after therapeutic lymph
      node dissection (TLND). METHODS: All consecutive FDG-PET-staged melanoma patients
      with palpable and cytologically proven lymph node metastases operated at our
      clinic between 2003 and 2011 were included. Disease-free survival and disease
      specific survival (DSS) were compared for nodal metastases in the groin, axilla,
      and neck regions by multivariable analysis. RESULTS: A total of 149 patients
      underwent TLND; there were 70 groin (47 %), 57 axillary (38 %), and 22 neck (15
      %) dissections. During a median follow-up of 18 (range 1-98) months, 102 patients
      (68 %) developed recurrent disease. Distant recurrence was the first sign of
      progressive disease in 78, 76, and 55 % of the groin, axilla, and neck groups,
      respectively (p = 0.26). Low involved/total lymph nodes (L/N) ratio (p < 0.001)
      and absence of extranodal growth pattern (p = 0.05) were independent predictors
      of a longer disease-free survival. For DSS, neck site of nodal metastasis (p =
      0.02) and low L/N ratio (p < 0.001) were independent predictors of long survival.
      The estimated 5-year DSS for the groin, axilla, and neck sites was 28, 34, and 66
      %, respectively. CONCLUSIONS: There seems significantly longer DSS after TLND for
      nodal macrometastases in the neck compared to axillary and groin sites, although
      larger series should confirm this finding.

PMID- 22588474
TI  - A strategy toward constructing a bifunctionalized MOF catalyst: post-synthetic
      modification of MOFs on organic ligands and coordinatively unsaturated metal
      sites.
AB  - A new strategy toward constructing bifunctionalized MOFs has been developed based
      on post-synthetic modification of MOFs on organic ligands and coordinatively
      unsaturated metal sites, respectively. Based on this strategy, an organo
      bifunctionalized MOF catalyst has been synthesized for the first time and
      successfully applied in one-pot tandem reaction.

PMID- 22588475
TI  - Does deployment to Iraq and Afghanistan affect respiratory health of US military
      personnel?
AB  - OBJECTIVE: To evaluate the association between postdeployment respiratory
      conditions and deployment to Iraq or Afghanistan. METHODS: We linked deployment
      history of US military personnel with postdeployment medical records. We then
      conducted a nested case-control study. RESULTS: Relative to a single deployment,
      multiple deployments were not significantly associated with obstructive pulmonary
      disease (odds ratio, 1.08; 95% confidence interval, 0.82 to 1.42). Cumulative
      time deployed was also not significantly associated with obstructive pulmonary
      disease. Nevertheless, we did note that the rate of respiratory symptoms and
      encounters for obstructive pulmonary diseases (predominantly asthma and
      bronchitis) increased from before to after deployment. CONCLUSIONS: In a
      population of active duty US military personnel, we observed an increase in
      postdeployment respiratory symptoms and medical encounters for obstructive
      pulmonary diseases, relative to predeployment rates, in the absence of an
      association with cumulative deployment duration or total number of deployments.

PMID- 22588476
TI  - Newly reported lupus and rheumatoid arthritis in relation to deployment within
      proximity to a documented open-air burn pit in Iraq.
AB  - OBJECTIVE: To assess the relationship between possible exposure to smoke from
      documented open-air burn pits and newly reported lupus and rheumatoid arthritis
      among Millennium Cohort participants who have deployed in support of operations
      in Iraq and Afghanistan. METHODS: Prospectively assessed self-reported lupus and
      rheumatoid arthritis among deployers who completed both 2004-2006 and 2007-2008
      questionnaires. RESULTS: After exclusions, more than 18,000 participants were
      deployed, including more than 3000 participants deployed within a 3-mile radius
      of a documented burn pit. After adjustment, proximity within 3 miles of a burn
      pit was not significantly associated with rheumatoid arthritis or lupus in
      general; however, one location was associated with lupus, although few cases were
      at this site (n = 2). CONCLUSIONS: Results indicate deployers potentially exposed
      to documented burn pits in the combined three-camp analysis were not at an
      elevated risk of lupus or rheumatoid arthritis.

PMID- 22588477
TI  - Overview and recommendations for medical screening and diagnostic evaluation for
      postdeployment lung disease in returning US warfighters.
AB  - OBJECTIVE: To review inhalational exposures and respiratory disease risks in US
      military personnel deployed to Iraq and Afghanistan and to develop consensus
      recommendations for medical screening and diagnostic referral. METHODS: A Working
      Group of physicians and exposure scientists from academia and from the
      Departments of Defense and Veterans Affairs was convened in February 2010.
      RESULTS: Despite uncertainty about the number of people affected and risk factors
      for adverse pulmonary outcomes in this occupational setting, the Working Group
      recommended: (1) standardized approaches to pre- and postdeployment medical
      surveillance; (2) criteria for medical referral and diagnosis; and (3) case
      definitions for major deployment-related lung diseases. CONCLUSIONS: There is a
      need for targeted, practical medical surveillance for lung diseases and for a
      standardized diagnostic approach for all symptomatic deployed personnel.

PMID- 22588478
TI  - Prevalence of environmental and other military exposure concerns in Operation
      Enduring Freedom and Operation Iraqi Freedom veterans.
AB  - OBJECTIVE: This study examined the prevalence of self-reported exposures in
      returning Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF) veterans
      and the relationship of exposure reports to current physical symptoms. METHODS:
      Using self-reports obtained immediately after return from deployment in a cohort
      of 760 enlisted Army reserve component military personnel, we assessed prevalence
      rates of environmental and other exposures and the association of these exposures
      to severity of physical symptoms. RESULTS: Reporting of environmental exposures
      was relatively low in veterans of OEF/OIF, but reporting more environmental and
      other exposures, in particular screening positive for a traumatic brain injury,
      was related to greater physical symptom severity immediately after deployment.
      CONCLUSIONS: Non-treatment-seeking, enlisted Army reserve component personnel
      reported relatively few exposures immediately after return from deployment;
      however, more exposures was modestly associated with greater severity of physical
      symptoms when controlling for predeployment symptoms, gender, and other
      deployment-related exposures.

PMID- 22588479
TI  - Validation of reference genes for real-time quantitative PCR normalization in
      soybean developmental and germinating seeds.
AB  - Most of traditional reference genes chosen for real-time quantitative PCR
      normalization were assumed to be ubiquitously and constitutively expressed in
      vegetative tissues. However, seeds show distinct transcriptomes compared with the
      vegetative tissues. Therefore, there is a need for re-validation of reference
      genes in samples of seed development and germination, especially for soybean
      seeds. In this study, we aimed at identifying reference genes suitable for the
      quantification of gene expression level in soybean seeds. In order to identify
      the best reference genes for soybean seeds, 18 putative reference genes were
      tested with various methods in different seed samples. We combined the outputs of
      both geNorm and NormFinder to assess the expression stability of these genes. The
      reference genes identified as optimums for seed development were TUA5 and UKN2,
      whereas for seed germination they were novel reference genes Glyma05g37470 and
      Glyma08g28550. Furthermore, for total seed samples it was necessary to combine
      four genes of Glyma05g37470, Glyma08g28550, Glyma18g04130 and UKN2 [corrected]
      for normalization. Key message We identified several reference genes that stably
      expressed in soybean seed developmental and germinating processes.

PMID- 22588480
TI  - Detection of viral RNA by fluorescence in situ hybridization (FISH).
AB  - Viruses that infect cells elicit specific changes to normal cell functions which
      serve to divert energy and resources for viral replication. Many aspects of host
      cell function are commandeered by viruses, usually by the expression of viral
      gene products that recruit host cell proteins and machineries. Moreover, viruses
      engineer specific membrane organelles or tag on to mobile vesicles and motor
      proteins to target regions of the cell (during de novo infection, viruses co-opt
      molecular motor proteins to target the nucleus; later, during virus assembly,
      they will hijack cellular machineries that will help in the assembly of viruses).
      Less is understood on how viruses, in particular those with RNA genomes,
      coordinate the intracellular trafficking of both protein and RNA components and
      how they achieve assembly of infectious particles at specific loci in the cell.
      The study of RNA localization began in earlier work. Developing lower eukaryotic
      embryos and neuronal cells provided important biological information, and also
      underscored the importance of RNA localization in the programming of gene
      expression cascades. The study in other organisms and cell systems has yielded
      similar important information. Viruses are obligate parasites and must utilise
      their host cells to replicate. Thus, it is critical to understand how RNA viruses
      direct their RNA genomes from the nucleus, through the nuclear pore, through the
      cytoplasm and on to one of its final destinations, into progeny virus particles.
      FISH serves as a useful tool to identify changes in steady-state localization of
      viral RNA. When combined with immunofluorescence (IF) analysis, FISH/IF co
      analyses will provide information on the co-localization of proteins with the
      viral RNA. This analysis therefore provides a good starting point to test for RNA
      protein interactions by other biochemical or biophysical tests, since co
      localization by itself is not enough evidence to be certain of an interaction. In
      studying viral RNA localization using a method like this, abundant information
      has been gained on both viral and cellular RNA trafficking events. For instance,
      HIV-1 produces RNA in the nucleus of infected cells but the RNA is only
      translated in the cytoplasm. When one key viral protein is missing (Rev), FISH of
      the viral RNA has revealed that the block to viral replication is due to the
      retention of the HIV-1 genomic RNA in the nucleus. Here, we present the method
      for visual analysis of viral genomic RNA in situ. The method makes use of a
      labelled RNA probe. This probe is designed to be complementary to the viral
      genomic RNA. During the in vitro synthesis of the antisense RNA probe, the
      ribonucleotide that is modified with digoxigenin (DIG) is included in an in vitro
      transcription reaction. Once the probe has hybridized to the target mRNA in
      cells, subsequent antibody labelling steps (Figure 1) will reveal the
      localization of the mRNA as well as proteins of interest when performing FISH/IF.

PMID- 22588481
TI  - Gustatory sensation of (L)- and (D)-amino acids in humans.
AB  - Amino acids are known to elicit complex taste, but most human psychophysical
      studies on the taste of amino acids have focused on a single basic taste, such as
      umami (savory) taste, sweetness, or bitterness. In this study, we addressed the
      potential relationship between the structure and the taste properties of amino
      acids by measuring the human gustatory intensity and quality in response to
      aqueous solutions of proteogenic amino acids in comparison to D-enantiomers.
      Trained subjects tasted aqueous solution of each amino acid and evaluated the
      intensities of total taste and each basic taste using a category-ratio scale.
      Each basic taste of amino acids showed the dependency on its hydrophobicity,
      size, charge, functional groups on the side chain, and chirality of the alpha
      carbon. In addition, the overall taste of amino acid was found to be the
      combination of basic tastes according to the partial structure. For example,
      hydrophilic non-charged middle-sized amino acids elicited sweetness, and L
      enantiomeric hydrophilic middle-sized structure was necessary for umami taste.
      For example, L-serine had mainly sweet and minor umami taste, and D-serine was
      sweet. We further applied Stevens' psychophysical function to relate the total
      taste intensity and the concentration, and found that the slope values depended
      on the major quality of taste (e.g., bitter large, sour small).

PMID- 22588482
TI  - Comparative proteome analysis of high and low cadmium accumulating soybeans under
      cadmium stress.
AB  - A comparative proteomic study was performed to unravel the protein networks
      involved in cadmium stress response in soybean. Ten-day-old seedlings of
      contrasting cadmium accumulating soybean cultivars-Harosoy (high cadmium
      accumulator), Fukuyutaka (low cadmium accumulator), and their recombinant inbred
      line CDH-80 (high cadmium accumulator) were exposed to 100 MUM CdCl(2) treatment
      for 3 days. Root growth was found to be affected under cadmium stress in all.
      Varietal differences at root protein level were evaluated. NADP-dependent alkenal
      double bond reductase P1 was found to be more abundant in low cadmium
      accumulating Fukuyutaka. Leaf proteome analysis revealed that differentially
      expressed proteins were primarily involved in metabolism and energy production.
      The results indicate that both high and low cadmium accumulating cultivars and
      CDH-80 share some common defense strategies to cope with the cadmium stress. High
      abundance of enzymes involved in glycolysis and TCA cycle might help cadmium
      challenged cells to produce more energy necessary to meet the high energy demand.
      Moreover, enhanced expressions of photosynthesis related proteins indicate quick
      utilization of photoassimilates in energy generation. Increased abundance of
      glutamine synthetase in all might be involved in phytochelatin mediated
      detoxification of cadmium ions. In addition, increased abundance of antioxidant
      enzymes, namely superoxide dismutase, ascorbate peroxidase, catalase, ensures
      cellular protection from reactive oxygen species mediated damages under cadmium
      stress. Enhanced expression of molecular chaperones in high cadmium accumulating
      cultivar might be another additional defense mechanism for refolding of misfolded
      proteins and to stabilize protein structure and function, thus maintain cellular
      homeostasis.

PMID- 22588483
TI  - Structure-based statistical analysis of transmembrane helices.
AB  - Recent advances in determination of the high-resolution structure of membrane
      proteins now enable analysis of the main features of amino acids in transmembrane
      (TM) segments in comparison with amino acids in water-soluble helices. In this
      work, we conducted a large-scale analysis of the prevalent locations of amino
      acids by using a data set of 170 structures of integral membrane proteins
      obtained from the MPtopo database and 930 structures of water-soluble helical
      proteins obtained from the protein data bank. Large hydrophobic amino acids (Leu,
      Val, Ile, and Phe) plus Gly were clearly prevalent in TM helices whereas polar
      amino acids (Glu, Lys, Asp, Arg, and Gln) were less frequent in this type of
      helix. The distribution of amino acids along TM helices was also examined. As
      expected, hydrophobic and slightly polar amino acids are commonly found in the
      hydrophobic core of the membrane whereas aromatic (Trp and Tyr), Pro, and the
      hydrophilic amino acids (Asn, His, and Gln) occur more frequently in the
      interface regions. Charged amino acids are also statistically prevalent outside
      the hydrophobic core of the membrane, and whereas acidic amino acids are
      frequently found at both cytoplasmic and extra-cytoplasmic interfaces, basic
      amino acids cluster at the cytoplasmic interface. These results strongly support
      the experimentally demonstrated biased distribution of positively charged amino
      acids (that is, the so-called the positive-inside rule) with structural data.

PMID- 22588485
TI  - Contour and persistence length of Corynebacterium diphtheriae pili by atomic
      force microscopy.
AB  - Many bacteria are characterized by nanoscale ultrastructures, for example S
      layers, flagella, fimbriae, or pili. The last two are especially important for
      attachment to different abiotic and biotic surfaces and for host-pathogen
      interactions. In this study, we investigated the geometric and elastic properties
      of pili of different Corynebacterium diphtheriae strains by atomic force
      microscopy (AFM). We performed quantitative contour-length analysis of bacterial
      pili and found that the visible contour length of the pili can be described by a
      log-normal distribution. Our data revealed significant strain-specific variations
      in the mean visible contour length of the pili, ranging from 260 to 1,590 nm. To
      estimate their full contour length, which is not directly accessible from the AFM
      images, we developed a simple correction model. Using this model, we determined
      the mean full contour length as 510-2,060 nm. To obtain the persistence length we
      used two different methods of analysis, one based on the end-to-end distance of
      the pili and one based on the bending angles of short segments. In comparison,
      the bending angle analysis proved to be more precise and resulted in persistence
      lengths in the narrow range of 220-280 nm, with no significant strain-specific
      variations. This is small compared with some other bacterial polymers, for
      example type IV pili, F-pili, or flagella.

PMID- 22588484
TI  - Model-based approaches for the determination of lipid bilayer structure from
      small-angle neutron and X-ray scattering data.
AB  - Some of our recent work has resulted in the detailed structures of fully
      hydrated, fluid phase phosphatidylcholine (PC) and phosphatidylglycerol (PG)
      bilayers. These structures were obtained from the joint refinement of small-angle
      neutron and X-ray data using the scattering density profile (SDP) models
      developed by Kucerka et al. (Biophys J 95:2356-2367, 2008; J Phys Chem B 116:232
      239, 2012). In this review, we first discuss models for the standalone analysis
      of neutron or X-ray scattering data from bilayers, and assess the strengths and
      weaknesses inherent to these models. In particular, it is recognized that
      standalone data do not contain enough information to fully resolve the structure
      of naturally disordered fluid bilayers, and therefore may not provide a robust
      determination of bilayer structure parameters, including the much-sought-after
      area per lipid. We then discuss the development of matter density-based models
      (including the SDP model) that allow for the joint refinement of different
      contrast neutron and X-ray data, as well as the implementation of local volume
      conservation within the unit cell (i.e., ideal packing). Such models provide
      natural definitions of bilayer thicknesses (most importantly the hydrophobic and
      Luzzati thicknesses) in terms of Gibbs dividing surfaces, and thus allow for the
      robust determination of lipid areas through equivalent slab relationships between
      bilayer thickness and lipid volume. In the final section of this review, we
      discuss some of the significant findings/features pertaining to structures of PC
      and PG bilayers as determined from SDP model analyses.

PMID- 22588486
TI  - Pediatric road traffic accident deaths presenting to a Nigerian referral center.
AB  - INTRODUCTION: Road traffic accident (RTA) is a common cause of pediatric trauma
      death and disability, constituting a worldwide loss of financial resources and
      potential manpower. This study was designed to determine the causes, prehospital
      care, presentation, and injuries that resulted in deaths among pediatric victims
      of RTA in Nigeria, and to make suggestions, based on the study data, to reduce
      RTA deaths. METHODS: This is a retrospective analysis of pediatric RTA presenting
      to a Nigerian referral center. The records of all pediatric RTA between January
      2006 and December 2010 at the University of Benin Teaching Hospital were analyzed
      for age, gender, causes of death, injury, rescue team prehospital treatment,
      injury to hospital arrival time, clinical condition on arrival, treatment,
      duration of hospitalization before death, challenges, and postmortem findings.
      RESULTS: Twenty-six (18%) of 143 pediatric RTA, comprising 18 males and 8
      females, between less than one and 18 (mean 9.3 +/- 5.2) years of age died. There
      was no significant statistical demographic difference observed when 15 (58%)
      deaths recorded among 67 (46.9%) children involved in motor vehicle accidents
      were compared with 11 (42%) involved in 76 (53.1%) motorcycle accidents (P =
      .31). More severe injuries resulting in the majority of deaths were associated
      with alcohol intoxication (P < .0001). Fourteen (54%) of the deaths were
      pedestrians, eight of whom were selling wares on the roadside; six were crossing
      roads that had no traffic signs or traffic control. Of the eight vehicle
      passengers who died, only two wore seat belts or used pediatric car seats, with
      no statistical significance compared to those who did not use seat belts or car
      seats (P = .37). Four of 14 front seat passengers and four of 32 rear seat
      passengers died (P = .222). Of motorcycle passengers, none of those who wore
      protective crash helmets died, while four died who were not wearing helmets.
      Passers-by and sympathizers served as rescuers provided emergency treatment, and
      presented the victims between one hour and four days after the accidents. Head
      injury in 14 (54%) cases was the most common cause of death. CONCLUSION:
      Pediatric RTA deaths in this study were due mainly to preventable causes. There
      is a need to stress road safety education to children, drivers, the general
      public and government policy formulators, and to adopt RTA preventive measures in
      this region of Nigeria.

PMID- 22588487
TI  - Effectiveness of live simulation of patients with intellectual disabilities.
AB  - This study investigated the use of live simulation using simulated patients
      portraying people with intellectual disabilities. The study sample consisted of
      173 health students. Using the simulation framework of Jeffries, students worked
      in groups of three; each student participated in at least one interaction with a
      simulated patient while the facilitator and other students in the group provided
      peer reflections. Students were given a specific task to complete with the
      patient simulator (e.g., obtaining a blood pressure reading). Student self
      confidence and satisfaction with the simulation was measured using a
      questionnaire followed by students' personal reflections and focus group
      feedback. Results indicate that students highly valued the simulation and thought
      it positively influenced direct care to patients with learning disabilities.

PMID- 22588490
TI  - Bacterial genetics: Hitting the CRISPR target.

PMID- 22588495
TI  - Effects of methylphenidate on basic and higher-order oculomotor functions.
AB  - Eye movements are sensitive indicators of pharmacological effects on sensorimotor
      and cognitive processing. Methylphenidate (MPH) is one of the most prescribed
      medications in psychiatry. It is increasingly used as a cognitive enhancer by
      healthy individuals. However, little is known of its effect on healthy cognition.
      Here we used oculomotor tests to evaluate the effects of MPH on basic oculomotor
      and executive functions. Twenty-nine males were given 20mg of MPH orally in a
      double-blind placebo-controlled crossover design. Participants performed visually
      guided saccades, sinusoidal smooth pursuit, predictive saccades and antisaccades
      one hour post-capsule administration. Heart rate and blood pressure were assessed
      prior to capsule administration, and again before and after task performance.
      Visually-guided saccade latency decreased with MPH (p<0.004). Smooth pursuit gain
      increased on MPH (p<0.001) and number of saccades during pursuit decreased
      (p<0.001). Proportion of predictive saccades increased on MPH (p<0.004),
      specifically in conditions with predictable timing. Peak velocity of predictive
      saccades increased with MPH (p<0.01). Antisaccade errors and latency were
      unaffected. Physiological variables were also unaffected. The effects on visually
      guided saccade latency and peak velocity are consistent with MPH effects on
      dopamine in basal ganglia. The improvements in predictive saccade conditions and
      smooth pursuit suggest effects on timing functions.

PMID- 22588496
TI  - Histological examination and evaluation of donor bile ducts received during
      orthotopic liver transplantation--a morphological clue to ischemic-type biliary
      lesion?
AB  - Ischemic-type biliary lesions (ITBL) belong to a group of biliary disorders that
      are regarded as the major complication in patients with orthotopic liver
      transplantation (OLT). We performed histological evaluation of donor common bile
      ducts received during OLT to find morphological clues to the pathomechanisms of
      ITBL. We investigated 93 grafts of 92 patients (recipients: mean age, 56.5 years;
      underlying disease: hepatocellular carcinoma (n = 45), alcoholic cirrhosis (n =
      16), viral hepatitis with cirrhosis (n = 9), retransplantations (n = 9), others
      (n = 14); donors: mean age, 53.2 years). Donor common bile ducts were received
      after recirculation of the hepatic artery prior to biliary end-to-end anastomosis
      and routinely processed. Statistical evaluation was performed by chi-square
      analysis and multivariate analysis using a logistic regression model. With regard
      to ITBL (observed in 19.4 %), the following phenomena were found to be
      statistically relevant: necrosis of the bile duct wall, arteriolonecrosis,
      vascular lesions (such as subintimal edema), and intramural bleeding (P < 0.001,
      P < 0.001, P = 0.029, and P = 0.031, respectively). In logistic regression
      analysis, arteriolonecrosis was the only parameter with significance (P = 0.001).
      Based on these results on the morphology of the donor common bile duct, we
      conclude that these phenomena of vascular damage, reflecting microangiopathy,
      play a major role in the pathogenesis of ITBL.

PMID- 22588497
TI  - Temporal differences of onset between primary skin lesions and regional lymph
      node lesions for tularemia in Japan: a clinicopathologic and immunohistochemical
      study of 19 skin cases and 54 lymph node cases.
AB  - For tularemia, a zoonosis caused by the gram-negative coccobacillus Francisella
      tularensis, research of the relation between skin lesions and lymph node lesions
      has not been reported in the literature. This report describes skin lesions and
      lymph node lesions and their mutual relation over time for tularemia in Japan.
      Around the second day after infection (DAI), a subcutaneous abscess was observed
      (abscess form). Hand and finger skin ulcers formed during the second to the
      fourth week. Subcutaneous and dermal granulomas were observed with adjacent
      monocytoid B lymphocytes (MBLs) (abscess-granulomatous form). From the sixth
      week, large granulomas with central homogeneous lesions emerged diffusely
      (granulomatous form). On 2-14 DAI, F. tularensis antigen in skin lesions was
      detected in abscesses. During 7-12 DAI, abscesses with adjacent MBLs appeared
      without epithelioid granuloma (abscess form) in regional lymph nodes. During the
      second to fifth week, granulomas appeared with necrosis (abscess-granulomatous
      form). After the sixth week, large granulomas with a central homogeneous lesion
      (granulomatous form) appeared. F. tularensis antigen in lymph node lesions was
      observed in the abscess on 7-92 DAI. Apparently, F. tularensis penetrates the
      finger skin immediately after contact with infected hares. Subsequently, the
      primary lesion gradually transfers from skin to regional lymph nodes. The
      regional lymph node lesions induced by skin lesion are designated as
      dermatopathic lymphadenopathy. This study revealed temporal differences of onset
      among the skin and lymph node lesions.

PMID- 22588498
TI  - DPP in the matrix mediates cell adhesion but is not restricted to stickiness: a
      tale of signaling.
AB  - Cell adhesion to DPP substrate is an integrin-mediated event and involves
      integrin binding, clustering, assembly of focal adhesion complexes and
      cytoskeletal organization. Cells perceive the DPP substrate through the integrin
      receptor alphavbeta1 and bind the actin cytoskeleton to the membrane via focal
      adhesion sites. The cells respond to this proteinaceous rigid substrate by
      activating the mechano-chemical signaling events leading to cell spreading and
      formation of focal adhesions. Focal adhesions, which are sites of integrin
      binding to the extracellular matrix, form in the leading edge during cell
      migration. These sites are dynamic and the supramolecular assemblies contain
      structural and signaling components regulating cell functions. In our study, we
      present a scenario that integrins utilize the actin network to permit activation
      of the mitogen-activated kinase modules to transduce signals through the
      cytoplasm to the nucleus in the presence of DPP. We specifically demonstrate that
      ERK-mediated transcriptional events impinge on activation of transcription
      factors leading to cell differentiation.

PMID- 22588499
TI  - Characterization of an extracellular lipase and its chaperone from Ralstonia
      eutropha H16.
AB  - Lipase enzymes catalyze the reversible hydrolysis of triacylglycerol to fatty
      acids and glycerol at the lipid-water interface. The metabolically versatile
      Ralstonia eutropha strain H16 is capable of utilizing various molecules
      containing long carbon chains such as plant oil, organic acids, or Tween as its
      sole carbon source for growth. Global gene expression analysis revealed an
      upregulation of two putative lipase genes during growth on trioleate. Through
      analysis of growth and activity using strains with gene deletions and
      complementations, the extracellular lipase (encoded by the lipA gene, locus tag
      H16_A1322) and lipase-specific chaperone (encoded by the lipB gene, locus tag
      H16_A1323) produced by R. eutropha H16 was identified. Increase in gene dosage of
      lipA not only resulted in an increase of the extracellular lipase activity, but
      also reduced the lag phase during growth on palm oil. LipA is a non-specific
      lipase that can completely hydrolyze triacylglycerol into its corresponding free
      fatty acids and glycerol. Although LipA is active over a temperature range from
      10  degrees C to 70  degrees C, it exhibited optimal activity at 50  degrees C.
      While R. eutropha H16 prefers a growth pH of 6.8, its extracellular lipase LipA
      is most active between pH 7 and 8. Cofactors are not required for lipase
      activity; however, EDTA and EGTA inhibited LipA activity by 83 %. Metal ions
      Mg(2+), Ca(2+), and Mn(2+) were found to stimulate LipA activity and relieve
      chelator inhibition. Certain detergents are found to improve solubility of the
      lipid substrate or increase lipase-lipid aggregation, as a result SDS and Triton
      X-100 were able to increase lipase activity by 20 % to 500 %. R. eutropha
      extracellular LipA activity can be hyper-increased, making the overexpression
      strain a potential candidate for commercial lipase production or in fermentations
      using plant oils as the sole carbon source.

PMID- 22588500
TI  - Characterization of Bifidobacterium spp. strains for the treatment of enteric
      disorders in newborns.
AB  - Several studies support the use of probiotics for the treatment of minor
      gastrointestinal problems in infants. Positive effects on newborn colics have
      been evidenced after administration of Lactobacillus strains, whereas no studies
      have been reported regarding the use of bifidobacteria for this purpose. This
      work was therefore aimed at the characterization of Bifidobacterium strains
      capable of inhibiting the growth of pathogens typical of the infant
      gastrointestinal tract and of coliforms isolated from colic newborns. Among the
      46 Bifidobacterium strains considered, 16 showed high antimicrobial activity
      against potential pathogens; these strains were further characterized from a
      taxonomic point of view, for the presence and transferability of antibiotic
      resistances, for citotoxic effects and adhesion to nontumorigenic gut epithelium
      cell lines. Moreover, their ability to stimulate gut health by increasing the
      metabolic activity and the immune response of epithelial cells was also studied.
      The examination of all these features allowed to identify three Bifidobacterium
      breve strains and a Bifidobacterium longum subsp. longum strain as potential
      probiotics for the treatments of enteric disorders in newborns such as infantile
      colics. A validation clinical trial involving the selected strains is being
      planned.

PMID- 22588501
TI  - Degradation and assimilation of aromatic compounds by Corynebacterium glutamicum:
      another potential for applications for this bacterium?
AB  - With the implementation of the well-established molecular tools and systems
      biology techniques, new knowledge on aromatic degradation and assimilation by
      Corynebacterium glutamicum has been emerging. This review summarizes recent
      findings on degradation of aromatic compounds by C. glutamicum. Among these
      findings, the mycothiol-dependent gentisate pathway was firstly discovered in C.
      glutamicum. Other important knowledge derived from C. glutamicum would be the
      discovery of linkages among aromatic degradation and primary metabolisms such as
      gluconeogenesis and central carbon metabolism. Various transporters in C.
      glutamicum have also been identified, and they play an essential role in
      microbial assimilation of aromatic compounds. Regulation on aromatic degradation
      occurs mainly at transcription level via pathway-specific regulators, but global
      regulator(s) is presumably involved in the regulation. It is concluded that C.
      glutamicum is a very useful model organism to disclose new knowledge of
      biochemistry, physiology, and genetics of the catabolism of aromatic compounds in
      high GC content Gram-positive bacteria, and that the new physiological properties
      of aromatic degradation and assimilation are potentially important for industrial
      applications of C. glutamicum.

PMID- 22588502
TI  - Engineering of formate dehydrogenase: synergistic effect of mutations affecting
      cofactor specificity and chemical stability.
AB  - Formate dehydrogenases (FDHs) are frequently used for the regeneration of
      cofactors in biotransformations employing NAD(P)H-dependent oxidoreductases.
      Major drawbacks of most native FDHs are their strong preference for NAD(+) and
      their low operational stability in the presence of reactive organic compounds
      such as alpha-haloketones. In this study, the FDH from Mycobacterium vaccae N10
      (MycFDH) was engineered in order to obtain an enzyme that is not only capable of
      regenerating NADPH but also stable toward the alpha-haloketone ethyl 4
      chloroacetoacetate (ECAA). To change the cofactor specificity, amino acids in the
      conserved NAD(+) binding motif were mutated. Among these mutants, MycFDH
      A198G/D221Q had the highest catalytic efficiency (k cat/K m) with NADP(+). The
      additional replacement of two cysteines (C145S/C255V) not only conferred a high
      resistance to ECAA but also enhanced the catalytic efficiency 6-fold. The
      resulting quadruple mutant MycFDH C145S/A198G/D221Q/C255V had a specific activity
      of 4.00 +/- 0.13 U mg(-1) and a K m, NADP(+) of 0.147 +/- 0.020 mM at 30  degrees
      C, pH 7. The A198G replacement had a major impact on the kinetic constants of the
      enzyme. The corresponding triple mutant, MycFDH C145S/D221Q/C255V, showed the
      highest specific activity reported to date for a NADP(+)-accepting FDH (v max,
      10.25 +/- 1.63 U mg(-1)). However, the half-saturation constant for NADP(+) (K m,
      NADP(+) , 0.92 +/- 0.10 mM) was about one order of magnitude higher than the one
      of the quadruple mutant. Depending on the reaction setup, both novel MycFDH
      variants could be useful for the production of the chiral synthon ethyl (S)-4
      chloro-3-hydroxybutyrate [(S)-ECHB] by asymmetric reduction of ECAA with NADPH
      dependent ketoreductases.

PMID- 22588503
TI  - Combination of site-directed mutagenesis and calcium ion addition for enhanced
      production of thermostable MBP-fused heparinase I in recombinant Escherichia
      coli.
AB  - Heparinase I (HepI), which specifically cleaves heparin and heparan sulfate, is
      one of the most extensively studied glycosaminoglycan lyases. Low productivity of
      HepI has largely hindered its industrial and pharmaceutical applications. Loss of
      bacterial HepI enzyme activity through poor thermostability during its expression
      and purification process in production can be an important issue. In this study,
      using a thermostabilization strategy combining site-directed mutagenesis and
      calcium ion addition during its production markedly improved the yield of maltose
      binding protein-fused HepI (MBP-HepI) from recombinant Escherichia coli.
      Substitution of Cys297 to serine in MBP-HepI offered a 30.6% increase in the
      recovered total enzyme activity due to a mutation-induced thermostabilizing
      effect. Furthermore, upon addition of Ca2+ as a stabilizer at optimized
      concentrations throughout its expression, extraction, and purification process,
      purified mutant MBP-HepI showed a specific activity of 56.3 IU/mg, 206% higher
      than that of the wild type obtained without Ca2+ addition, along with a 177%
      increase in the recovered total enzyme activity. The enzyme obtained through this
      novel approach also exhibited significantly enhanced thermostability, as
      indicated by both experimental data and the kinetic modeling. High-yield
      production of thermostable MBP-HepI using the present system will facilitate its
      applications in laboratory-scale heparin analysis as well as industrial-scale
      production of low molecular weight heparin as an improved anticoagulant
      substitute.

PMID- 22588504
TI  - In vitro and in vivo investigations of upconversion and NIR emitting
      Gd2O3:Er3+,Yb3+ nanostructures for biomedical applications.
AB  - The use of an "over 1000-nm near-infrared (NIR) in vivo fluorescence bioimaging"
      system based on lanthanide containing inorganic nanostructures emitting in the
      visible and NIR range under 980-nm excitation is proposed. It may overcome
      problems of currently used biomarkers including color fading, phototoxicity and
      scattering. Gd(2)O(3):Er(3+),Yb(3+) nanoparticles and nanorods showing
      upconversion and NIR emission are synthesized and their cytotoxic behavior is
      investigated by incubation with B-cell hybridomas and macrophages. Surface
      modification with PEG-b-PAAc provides the necessary chemical durability reducing
      the release of toxic Gd(3+) ions. NIR fluorescence microscopy is used to
      investigate the suitability of the nanostructures as NIR-NIR biomarkers. The in
      vitro uptake of bare and modified nanostructures by macrophages is investigated
      by confocal laser scanning microscopy. In vivo investigations revealed
      nanostructures in liver, lung, kidneys and spleen a few hours after injection
      into mice, while most of the nanostructures have been removed from the body after
      24 h.

PMID- 22588505
TI  - Hematoma-inspired alginate/platelet releasate/CaPO4 composite: initiation of the
      inflammatory-mediated response associated with fracture repair in vitro and ex
      vivo injection delivery.
AB  - A clinical need continues for consistent bone remodeling within problematic sites
      such as those of fracture nonunion, avascular necrosis, or irregular bone
      formations. In attempt to address such needs, a biomaterial system is proposed to
      induce early inflammatory responses after implantation and to provide later
      osteoconductive scaffolding for bone regeneration. Biomaterial-induced
      inflammation would parallel the early stage of hematoma-induced fracture repair
      and allow scaffold-promoted remodeling of osseous tissue to a healthy state.
      Initiation of the wound healing cascade by two human concentrated platelet
      releasate-containing alginate/beta-tricalcium phosphate biocomposites has been
      studied in vitro using the TIB-71TM RAW264.7 mouse monocyte cell line.
      Inflammatory responses inherent to the base material were found and could be
      modulated through incorporation of platelet releasate. Differences in hydrogel
      wt% (2 vs. 8 %) and/or calcium phosphate granule vol.% (20 vs. 10 %) allowed for
      tuning the response associated with platelet releasate-associated growth factor
      elution. Tunability from completely suppressing the inflammatory response to
      augmenting the response was observed through varied elution profiles of both
      releasate-derived bioagents and impurities inherent to alginate. A 2.5-fold
      upregulation of inducible-nitric oxide synthase gene expression followed by a
      tenfold increase in nitrite media levels was induced by inclusion of releasate
      within the 8 wt%/10 vol.% formulation and was comparable to an endotoxin positive
      control. Whereas, near complete elimination of inflammation was seen when
      releasate was included within the 2 wt%/20 vol.% formulation. These in vitro
      results suggested tunable interactions between the multiple platelet releasate
      derived bioagents and the biocomposites for enhancing hematoma-like fracture
      repair. Additionally, minimally invasive delivery for in situ curing of the
      implant system via injection was demonstrated in rat tail vertebrae using
      microcomputed tomography.

PMID- 22588506
TI  - The origins and evolution of ubiquitination sites.
AB  - Protein ubiquitination is central to the regulation of various pathways in
      eukaryotes. The process of ubiquitination and its cellular outcome were
      investigated in hundreds of proteins to date. Despite this, the evolution of this
      regulatory mechanism has not yet been addressed comprehensively. Here, we
      quantify the rates of evolutionary changes of ubiquitination and SUMOylation
      (Small Ubiquitin-like MOdifier) sites. We estimate the time at which they first
      appeared, and compare them to acetylation and phosphorylation sites and to
      unmodified residues. We observe that the various modification sites studied
      exhibit similar rates. Mammalian ubiquitination sites are weakly more conserved
      than unmodified lysine residues, and a higher degree of relative conservation is
      observed when analyzing bona fide ubiquitination sites. Various reasons can be
      proposed for the limited level of excess conservation of ubiquitination,
      including shifts in locations of the sites, the presence of alternative sites,
      and changes in the regulatory pathways. We observe that disappearance of sites
      may be compensated by the presence of a lysine residue in close proximity, which
      is significant when compared to evolutionary patterns of unmodified lysine
      residues, especially in disordered regions. This emphasizes the importance of
      analyzing a window in the vicinity of functional residues, as well as the
      capability of the ubiquitination machinery to ubiquitinate residues in a certain
      region. Using prokaryotic orthologs of ubiquitinated proteins, we study how
      ubiquitination sites were formed, and observe that while sometimes sequence
      additions and rearrangements are involved, in many cases the ubiquitination
      machinery utilizes an already existing sequence without significantly changing
      it. Finally, we examine the evolution of ubiquitination, which is linked with
      other modifications, to infer how these complex regulatory modules have evolved.
      Our study gives initial insights into the formation of ubiquitination sites,
      their degree of conservation in various species, and their co-evolution with
      other posttranslational modifications.

PMID- 22588507
TI  - [Mask ventilation before relaxation. From dogma to individuality].

PMID- 22588508
TI  - Use of video feedback intervention in an inpatient perinatal psychiatric setting
      to improve maternal parenting.
AB  - This study utilizes video feedback to improve maternal parenting behavior in
      clinically depressed mothers admitted to a perinatal inpatient psychiatric unit.
      Depressed mothers (n = 74) were randomized to "video" (n = 25), "verbal" (n =
      26), or "standard care" (n = 23). "Video" mothers were taped playing with their
      infant; interaction was reviewed with a mental health specialist. "Verbal"
      mothers only discussed interaction with their infant. "Standard care" mothers
      received only routine inpatient care. Mothers were assessed for mental health
      status, perceptions of baby behavior, and parenting competence. There was
      significant improvement in mental health status of all participants, regardless
      of intervention. Neither intervention had an advantage, compared to standard
      care, in improving parenting confidence or perceptions of infant behavior. Video
      mothers were more likely to report no change in their parenting confidence the
      more feedback sessions completed. The number of intervention sessions for each
      participant was limited by the duration of their inpatient admission. Most
      participants were on simultaneous pharmacotherapy and psychotherapy, as well as
      receiving intensive mothercraft assistance; this may have influenced intervention
      effectiveness. Results suggest that this type of intervention may be beneficial,
      but in the current format does not add sufficiently to standard care to be
      detected by the measures used.

PMID- 22588509
TI  - The effect of having multiple providers on antidepressant discontinuation in
      pregnancy: a case report.

PMID- 22588510
TI  - Maternal expectations of postpartum social support: validation of the Postpartum
      Social Support Questionnaire during pregnancy.
AB  - Thirteen percent of women experience postpartum depression. Prenatal screening
      for anticipated postpartum social support, a postpartum depression risk factor,
      may allow for early intervention. We sought to validate use of a modified version
      of the Postpartum Social Support Questionnaire (PSSQ) in pregnant women at
      increased risk for postpartum depression. Factor analysis using orthogonal
      varimax rotation was used. The modified PSSQ, administered during pregnancy,
      yields similar loading patterns as observed in postpartum administration of the
      original PSSQ.

PMID- 22588511
TI  - Introduction to the special issue on micro- and nanofabrication techniques.

PMID- 22588512
TI  - Sensory systems: Great (taste) expectations.

PMID- 22588513
TI  - Neurotransmission: Autophagy regulates transmission.

PMID- 22588514
TI  - Asymmetric Friedel-Crafts alkylation of indoles with 3-nitro-2H-chromenes
      catalyzed by diphenylamine-linked bis(oxazoline) and bis(thiazoline) Zn(II)
      complexes.
AB  - An efficient diastereo- and enantioselective Friedel-Crafts alkylation of indoles
      with 3-nitro-2H-chromenes catalyzed by diphenylamine-linked bis(oxazoline) and
      bis(thiazoline) Zn(II) complexes has been developed. This asymmetric Friedel
      Crafts alkylation led to medicinally privileged indolyl(nitro)chromans in good
      yields with high enantioselectivities (up to 95% ee) and diastereoselectivities
      under mild reaction conditions.

PMID- 22588516
TI  - Water-soluble Au-CeO2 hybrid nanosheets with high catalytic activity and
      recyclability.
AB  - A facile one-pot aqueous method has been fabricated for synthesis of Au-CeO(2)
      hybrid nanosheets. L-Lysine molecules are employed as the junctor to connect the
      two components of Au and CeO(2) nanoparticles. The obtained catalysts exhibited
      high catalytic activity, stability, and recyclability for the reduction reaction
      of p-nitrophenol into p-aminophenol by NaBH(4).

PMID- 22588515
TI  - Production and carbon allocation in monocultures and mixed-species plantations of
      Eucalyptus grandis and Acacia mangium in Brazil.
AB  - Introducing nitrogen-fixing tree species in fast-growing eucalypt plantations has
      the potential to improve soil nitrogen availability compared with eucalypt
      monocultures. Whether or not the changes in soil nutrient status and stand
      structure will lead to mixtures that out-yield monocultures depends on the
      balance between positive interactions and the negative effects of interspecific
      competition, and on their effect on carbon (C) uptake and partitioning. We used a
      C budget approach to quantify growth, C uptake and C partitioning in monocultures
      of Eucalyptus grandis (W. Hill ex Maiden) and Acacia mangium (Willd.) (treatments
      E100 and A100, respectively), and in a mixture at the same stocking density with
      the two species at a proportion of 1 : 1 (treatment MS). Allometric relationships
      established over the whole rotation, and measurements of soil CO(2) efflux and
      aboveground litterfall for ages 4-6 years after planting were used to estimate
      aboveground net primary production (ANPP), total belowground carbon flux (TBCF)
      and gross primary production (GPP). We tested the hypotheses that (i) species
      differences for wood production between E. grandis and A. mangium monocultures
      were partly explained by different C partitioning strategies, and (ii) the
      observed lower wood production in the mixture compared with eucalypt monoculture
      was mostly explained by a lower partitioning aboveground. At the end of the
      rotation, total aboveground biomass was lowest in A100 (10.5 kg DM m(-2)),
      intermediate in MS (12.2 kg DM m(-2)) and highest in E100 (13.9 kg DM m(-2)). The
      results did not support our first hypothesis of contrasting C partitioning
      strategies between E. grandis and A. mangium monocultures: the 21% lower growth
      (DeltaB(w)) in A100 compared with E100 was almost entirely explained by a 23%
      lower GPP, with little or no species difference in ratios such as TBCF/GPP,
      ANPP/TBCF, DeltaB(w)/ANPP and DeltaB(w)/GPP. In contrast, the 28% lower DeltaB(w)
      in MS than in E100 was explained both by a 15% lower GPP and by a 15% lower
      fraction of GPP allocated to wood growth, thus partially supporting our second
      hypothesis: mixing the two species led to shifts in C allocations from above- to
      belowground, and from growth to litter production, for both species.

PMID- 22588517
TI  - Formal asymmetric enone aminohydroxylation: organocatalytic one-pot synthesis of
      4,5-disubstituted oxazolidinones.
AB  - A formal asymmetric organocatalytic aminohydroxylation reaction of enones has
      been achieved via an aziridination-double S(N)2 sequence. As a part of the
      reaction design, the generated amino alcohol products are isolated as the
      corresponding oxazolidinones in good yields and excellent stereoselectivities.

PMID- 22588518
TI  - Quantitative elastography of renal transplants using supersonic shear imaging: a
      pilot study.
AB  - PURPOSE: To evaluate the reliability of quantitative ultrasonic measurement of
      renal allograft elasticity using supersonic shear imaging (SSI) and its
      relationship with parenchymal pathological changes. MATERIALS AND METHODS: Forty
      three kidney transplant recipients (22 women, 21 men) (mean age, 51 years; age
      range, 18-70 years) underwent SSI elastography, followed by biopsy. The
      quantitative measurements of cortical elasticity were performed by two
      radiologists and expressed in terms of Young's modulus (kPa). Intra- and inter
      observer reproducibility was assessed (Kruskal-Wallis test and Bland-Altman
      analysis), as well as the correlation between elasticity values and clinical,
      biological and pathological data (semi-quantitative Banff scoring). Interstitial
      fibrosis was evaluated semi-quantitatively by the Banff score and measured by
      quantitative image analysis. RESULTS: Intra- and inter-observer variation
      coefficients of cortical elasticity were 20 % and 12 %, respectively. Renal
      cortical stiffness did not correlate with any clinical parameters, any single
      semi-quantitative Banff score or the level of interstitial fibrosis; however, a
      significant correlation was observed between cortical stiffness and the total
      Banff scores of chronic lesions and of all elementary lesions (R = 0.34, P = 0.05
      and R = 0.41, P = 0.03,respectively). CONCLUSION: Quantitative measurement of
      renal cortical stiffness using SSI is a promising non-invasive tool to evaluate
      global histological deterioration. KEY POINTS : * Supersonic shear imaging
      elastography can measure cortical stiffness in renal transplants * The level of
      cortical stiffness is correlated with the global degree of tissue lesions * The
      global histological deterioration of transplanted kidneys can be quantified using
      elastography.

PMID- 22588520
TI  - QuikClot combat gauze for hemorrhage control.

PMID- 22588519
TI  - Dual energy CT in patients with polycystic kidney disease.
AB  - OBJECTIVES: To evaluate the diagnostic efficacy of dual source-dual energy CT
      (DECT) in the detection of neoplasia in patients with polycystic kidney disease
      (PKD). METHODS: A total of 21 patients with PKD underwent DECT on a dual source
      system, using kVp settings of Sn140/100 or 140/80. Colour-coded iodine maps and
      virtual unenhanced images were used to determine enhancement within cysts and to
      differentiate haemorrhagic from simple cysts. A cut-off of 15 HU was used as a
      threshold for malignancy. In patients with malignancy, histopathology was the
      gold standard; otherwise, patients underwent follow-up imaging for 150-908 days.
      RESULTS: On the basis of measured enhancement, 13 enhancing masses were seen in 4
      patients (12 renal cell cancers and 1 adenoma); follow-up imaging showed no
      malignancy in 18 patients. Cysts did not enhance by more than 15 HU, whereas
      masses showed a mean enhancement of 45 (25-123) HU. Average radiation exposure
      was 9.6 mSv for the biphasic protocol and 5.8 mSv for DECT only. CONCLUSION: DECT
      greatly facilitates the detection of malignancy in patients with polycystic
      kidney disease, at the same time reducing radiation exposure by omission of a
      true unenhanced phase. KEY POINTS : * Identification of tumours within polycystic
      kidneys can be difficult. * Dual energy computed tomography (DECT) provides two
      separate sets of images. * Iodine maps and virtual non-enhanced (VNE) images can
      then be calculated. * DECT facilitates screening for potential renal tumours in
      polycystic kidneys.

PMID- 22588521
TI  - Educational paper: do we need neonatal clinical pharmacologists?
AB  - Effective and safe drug administration in young infants should be based on
      integrated knowledge concerning the evolving physiological characteristics of the
      infant who will receive the drug and the pharmacokinetic and pharmacodynamic
      characteristics of a given drug. Consequently, clinical pharmacology in neonates
      is as dynamic and diverse as the neonates we are entitled to take care of. Even
      more than median estimates, covariates of variability within the population are
      of clinical relevance. We aim to illustrate the complexity and the need for
      neonatal clinical pharmacology based on the gap between current and likely best
      clinical practice for two commonly administered compounds (aminoglycosides for
      infection and ibuprofen for patent ductus arteriosus) and one new compound
      (bevacizumab, to treat threshold retinopathy of prematurity). Progression has
      been made to render pharmacokinetic studies child size, e.g., low volume samples,
      optimal study design, and population pharmacokinetics. Challenges to further
      improve clinical pharmacology in neonates include, when appropriate, the
      validation of off-patent drug dosing regimens and of infant-tailored
      formulations. Knowledge integration, i.e., the use of available data to improve
      current drug use and to predict pharmacokinetics/pharmacodynamics for similar
      compounds is needed. Development of clinical research networks is helpful to
      achieve these goals.

PMID- 22588522
TI  - Induction of adhesion-dependent signals using low-intensity ultrasound.
AB  - In multicellular organisms, cell behavior is dictated by interactions with the
      extracellular matrix. Consequences of matrix-engagement range from regulation of
      cell migration and proliferation, to secretion and even differentiation. The
      signals underlying each of these complex processes arise from the molecular
      interactions of extracellular matrix receptors on the surface of the cell.
      Integrins are the prototypic receptors and provide a mechanical link between
      extracellular matrix and the cytoskeleton, as well as initiating some of the
      adhesion-dependent signaling cascades. However, it is becoming increasingly
      apparent that additional transmembrane receptors function alongside the integrins
      to regulate both the integrin itself and signals downstream. The most elegant of
      these examples is the transmembrane proteoglycan, syndecan-4, which cooperates
      with alpha(5)beta(1)-integrin during adhesion to fibronectin. In vivo models
      demonstrate the importance of syndecan-4 signaling, as syndecan-4-knockout mice
      exhibit healing retardation due to inefficient fibroblast migration. In wild-type
      animals, migration of fibroblasts toward a wound is triggered by the appearance
      of fibronectin that leaks from damaged capillaries and is deposited by
      macrophages in injured tissue. Therefore there is great interest in discovering
      strategies that enhance fibronectin-dependent signaling and could accelerate
      repair processes. The integrin-mediated and syndecan-4-mediated components of
      fibronectin-dependent signaling can be separated by stimulating cells with
      recombinant fibronectin fragments. Although integrin engagement is essential for
      cell adhesion, certain fibronectin-dependent signals are regulated by syndecan-4.
      Syndecan-4 activates the Rac1 protrusive signal, causes integrin redistribution,
      triggers recruitment of cytoskeletal molecules, such as vinculin, to focal
      adhesions, and thereby induces directional migration. We have looked for
      alternative strategies for activating such signals and found that low-intensity
      pulsed ultrasound (LIPUS) can mimic the effects of syndecan-4 engagement. In this
      protocol we describe the method by which 30 mW/cm(2), 1.5 MHz ultrasound, pulsed
      at 1 kHz (Fig. 1) can be applied to fibroblasts in culture (Fig. 2) to induce
      Rac1 activation and focal adhesion formation. Ultrasound stimulation is applied
      for a maximum of 20 minutes, as this combination of parameters has been found to
      be most efficacious for acceleration of clinical fracture repair. The method uses
      recombinant fibronectin fragments to engage alpha(5)beta(1)-integrin, without
      engagement of syndecan-4, and requires inhibition of protein synthesis by
      cycloheximide to block deposition of additional matrix by the fibroblasts. The
      positive effect of ultrasound on repair mechanisms is well documented, and by
      understanding the molecular effect of ultrasound in culture we should be able to
      refine the therapeutic technique to improve clinical outcomes.

PMID- 22588524
TI  - [Patella luxation].

PMID- 22588525
TI  - [Acute osteochondral lesions after patella dislocation].
AB  - Acute osteochondral lesions of the knee are injuries often caused by patella
      dislocations. In cases of negative standard x-rays magnetic resonance imaging
      (MRI) scans should be used to exclude these injuries, as even large fragments can
      escape visualization with x-rays. These lesions are strong indications for
      surgical intervention especially if refixation is considered. The intra-articular
      defect is visualized using arthroscopy and the dislocated fragment is retrieved
      entirely. Inspection of the fragment is performed ex situ to determine whether or
      not refixation should be performed. The refixation technique to be used for
      lesions in the femoro-patellar joint depends on fragment size and defect site.
      Current biodegradable implants have demonstrated good clinical results without
      the need for implant removal. The rehabilitation protocol should be
      individualized to the patient, size and site of the defect.

PMID- 22588526
TI  - [Chronic patellofemoral instability].
AB  - Chronic patellofemoral instability may lead to pain and early osteoarthrosis.
      Recurrent dislocations of the patella, lateral subluxation and chronic
      dislocation are summarized under this generic term. There are five different
      factors which may be responsible of the development of chronic patellofemoral
      instability: 1) elongation of the medial patellofemoral ligament (MPFL), 2)
      patella alta, 3) increased distance between tibial tuberosity and trochlea groove
      (TTTG) distance, 4) trochlea dysplasia and 5) torsional malalignment. To rule out
      these factors clinical examination, radiological diagnostics (luxation,
      subluxation in the Defilee view, trochlea morphology, patella alta) and magnetic
      resonance imaging (MRI) of TTTG distance and trochlea morphology are crucial. The
      indications of operative treatment are chronic pain with subluxation, chronic
      dislocation and recurrent dislocation. Currently the former frequently and
      universally used lateral release is only indicated in cases of subluxation and
      positive tilt. Biomechanical studies have shown that a lateral release will
      otherwise increase patellofemoral instability. The choice of the surgical
      technique depends on the factors underlying patellofemoral instability, the
      conditions of growth plate and cartilage damage. Among the different surgical
      options proximal and distal realignment procedures are differentiated. In cases
      of MPFL elongation and mild passive instability a medial reefing might be
      successful. In cases of MPFL elongation, high passive instability up to 30
      degrees  of flexion (with or without trochlear dysplasia) MPFL reconstruction may
      be the treatment of choice. A trochleoplasty is rarely indicated. This treatment
      may be considered in cases of high grade trochlea dysplasia and passive
      instability at more than 30 degrees  of flexion. If the TTTG distance is
      increased (>20 mm) or in cases of patella alta distal realignment with tibial
      tubercle transfer should be considered. This operation might also be useful in
      the presence of lateral cartilage damage as an anteromedialization of the
      patella.

PMID- 22588527
TI  - Early diagnosis of impending femoral insufficiency fractures by use of MRI: case
      report and review of the literature.

PMID- 22588528
TI  - Evaluation of an integrated intensive care unit monitoring display by critical
      care fellow physicians.
AB  - In the past two far-view displays, which showed vital signs, trends, alarms,
      infusion pump status, and therapy support indicators, were developed and assessed
      by critical care nurses (Gorges et al. in Dimens Crit Care Nurs. 30(4):206-17,
      2011). The aim of the current study is to assess the generalizability of these
      findings to physicians. The first aim is to test whether an integrated far-view
      display, designed to be readable from 3 to 5 m, enables critical care physicians
      to more rapidly and accurately (1) recognize a change in patient condition; (2)
      identify alarms; and (3) identify near-empty infusion pumps, than a traditional
      patient monitor and infusion pump. A second aim is to test if the new displays
      reduce the mental workload required for this decision making. Fifteen critical
      care fellow physicians (median age of 34 years, with 2-8 years of ICU experience)
      were asked to use the three displays to compare the data from two patients and
      decide which patient required their attention first. Each physician made 60
      decisions: 20 with each of the two far-view displays and 20 decisions with a
      standard patient monitor next to an infusion pump. A 41 and 26 % improvement in
      decision accuracy was observed with the bar and clock far-view displays,
      respectively. Specifically, the identification of near empty infusion pumps, a
      task normally performed by nurses, and patients with a single alarm were better
      with the new displays. Using the bar display physicians made their decision 12 %
      faster than when using the control display, a median improvement of 2.1 s. No
      significant differences were observed in measured workload. Displays that present
      patient data in a redesigned format enables critical care clinicians to more
      rapidly identify changes in patient conditions and to more accurately decide
      which patient needs their attention. In a clinical setting, this could improve
      patient safety. In future work, an evaluation of the display using live patient
      data from an ICU should be performed.

PMID- 22588529
TI  - Cost-utility analysis of the housing and health intervention for homeless and
      unstably housed persons living with HIV.
AB  - We present a cost-utility analysis based on data from the Housing and Health
      (H&H) Study of rental assistance for homeless and unstably housed persons living
      with HIV in Baltimore, Chicago and Los Angeles. As-treated analyses found
      favorable associations of housing with HIV viral load, emergency room use, and
      perceived stress (an outcome that can be quantitatively linked to quality of
      life). We combined these outcome data with information on intervention costs to
      estimate the cost-per-quality-adjusted-life-year (QALY) saved. We estimate that
      the cost-per-QALY-saved by the HIV-related housing services is $62,493. These
      services compare favorably (in terms of cost-effectiveness) to other well
      accepted medical and public health services.

PMID- 22588530
TI  - Inflammatory cytokine and chemokine expression is associated with heterotopic
      ossification in high-energy penetrating war injuries.
AB  - OBJECTIVE: Heterotopic ossification (HO) develops frequently after modern high
      energy penetrating war injuries. The purpose of this prospective study was to
      identify and characterize the unique cytokine and chemokine profile associated
      with the development of HO as it pertained to the systemic inflammatory response
      after penetrating combat-related trauma. METHODS: Patients with high-energy
      penetrating extremity wounds were prospectively enrolled. Surgical debridement
      along with the use of a pulse lavage and vacuum-assisted-closure device was
      performed every 48-72 hours until definitive wound closure. Wound bed tissue
      biopsy, wound effluent, and serum were collected before each debridement.
      Effluent and serum were analyzed for 22 relevant cytokines and chemokines. Tissue
      was analyzed quantitatively for bacterial colonization. Correlations between
      specific wound and patient characteristics were also analyzed. The primary
      clinical outcome measure was the formation of HO as confirmed by radiographs at a
      minimum of 2 months of follow-up. RESULTS: Thirty-six penetrating extremity war
      wounds in 24 patients were investigated. The observed rate of HO in the study
      population was 38%. Of the 36 wounds, 13 (36%) demonstrated HO at a minimum
      follow-up of 2 months. An elevated injury severity score was associated with the
      development of HO (P = 0.006). Wound characteristics that correlated with the
      development of HO included impaired healing (P = 0.005) and bacterial
      colonization (P < 0.001). Both serum (interleukin-6, interleukin-10, and MCP-1)
      and wound effluent (IP-10 and MIP-1alpha) cytokine and chemokine bioprofiles were
      individually associated and suggestive of the development of HO (P < 0.05).
      CONCLUSIONS: A severe systemic and wound-specific inflammatory state as evident
      by elevated levels of inflammatory cytokines, elevated injury severity score, and
      bacterial wound colonization is associated with the development of HO. These
      findings suggest that the development of HO in traumatic combat-related wounds is
      associated with a hyper-inflammatory systemic response to injury. LEVEL OF
      EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 22588531
TI  - Biomechanical effects of the nail entry zone and anterior cortical bone loss on
      the proximal tibia.
AB  - OBJECTIVES: The aims of this study were as follows: to determine if the presence
      of the nail entry zone alters the biomechanics of the proximal tibia after
      intramedullary (IM) nailing using a computational model; to determine if nail
      removal restores normal biomechanics to the proximal tibia; and to determine if
      these effects are magnified with anterior cortical bone loss. METHODS: Three
      dimensional finite element (FE) tibial models were developed and used for this
      study: an intact tibia, a nailed tibia, and a tibia with the nail removed. One
      matched pair of fresh-frozen cadaver tibias was obtained to construct and
      validate the FE model. The tibias underwent computed tomography scanning, and
      geometric models were obtained from computed tomography data through volumetric
      reconstruction. The left tibia was implanted with an unlocked IM nail. The
      experimental validation of the models was performed by comparing experimental and
      FE data. Anterior cortical bone of the proximal tibia was removed down to the
      tibial tubercle on the models to simulate a worst-case scenario of its removal
      during an IM nailing procedure. Three load cases were considered for each FE
      tibial model: standing, walking, and single-limb kneeling. RESULTS: The principal
      strain values of the proximal tibia with the nail entry zone were increased in
      comparison to the intact tibia in all 3 loading scenarios (+350%-550%). These
      effects were greatly magnified with anterior cortical bone loss near the nail
      entry zone (6-fold increase). The presence of the nail increased the principal
      strain values in the proximal tibia both with an intact and a disrupted anterior
      cortex in all loading scenarios, and these values remain elevated even with
      removal of the nail. The values predicted by the FE model were in good agreement
      with the experimentally measured strains (R = 0.92). CONCLUSION: The nail entry
      zone in the proximal tibia greatly increases the principle strain values when
      standing, walking, and kneeling. The presence of the nail results in the highest
      strain values, but they do not return to normal when the nail is removed. These
      effects are significantly amplified with removal of the anterior tibial cortex
      near the nail entry zone.

PMID- 22588532
TI  - Stress-induced hyperglycemia as a risk factor for surgical-site infection in
      nondiabetic orthopedic trauma patients admitted to the intensive care unit.
AB  - OBJECTIVES: The aim of this study was to evaluate the association between stress
      induced hyperglycemia and infectious complications in nondiabetic orthopedic
      trauma patients admitted to the intensive care unit (ICU). DESIGN: : This study
      was a retrospective review. SETTING: The study was conducted at an academic level
      1 trauma center. PATIENTS: One hundred and eighty-seven consecutive trauma
      patients with isolated orthopedic injuries were studied. INTERVENTION: : Blood
      glucose values during initial hospitalization were evaluated. The admission blood
      glucose (BG) and hyperglycemic index (HGI) were determined for each patient. MAIN
      OUTCOME MEASURES: Perioperative infectious complications: pneumonia, urinary
      tract infection (UTI), surgical-site infection (SSI), sepsis were the outcome
      measures. RESULTS: An average of 21.5 BG values was obtained for each patient.
      The mean ICU and hospital length of stay was 4.0 +/- 4.9 and 10.0 +/- 8.1 days,
      respectively. Infections were recorded in 43 of 187 patients (23.0%) and SSIs
      specifically documented in 16 patients (8.6%). Open fractures were not associated
      with SSI (8/83, 9.6% vs. 8/104, 7.7%). There was no difference in admission BG or
      HGI and infection. However, there was a significant difference in HGI when
      considering SSI alone (2.1 +/- 1.7 vs. 1.2 +/- 1.1). Patients with an SSI
      received a greater amount of blood transfusions (14.9 +/- 12.1 vs. 4.9 +/- 7.6).
      No patient was diagnosed with a separate infection (ie, pneumonia, UTI,
      bacteremia) before SSI. There was no significant difference in injury severity
      score among patients with an SSI (11.1 +/- 4.0 vs. 9.6 +/- 3.0). Multivariable
      regression testing with HGI as a continuous variable demonstrated a significant
      relationship (odds ratio: 1.8, 95% confidence interval: 1.3-2.5) with SSI after
      adjusting for blood transfusions (odds ratio: 1.1, 95% confidence interval: 1.1
      1.2). CONCLUSIONS: : Stress-induced hyperglycemia demonstrated a significant
      independent association with SSIs in nondiabetic orthopedic trauma patients who
      were admitted to the ICU. LEVEL OF EVIDENCE: Prognostic Level II. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 22588533
TI  - Invited commentary: the importance of hyperglycemia control in orthopedic trauma
      patients.

PMID- 22588534
TI  - A platelet target for venous thrombosis? P2Y1 deletion or antagonism protects
      mice from vena cava thrombosis.
AB  - A role for platelets in the pathogenesis of venous thrombosis was suggested by
      clinical and preclinical studies. However, examination of the platelet receptor,
      P2Y1, in this area has been limited. The goal of the current study was to examine
      effects of P2Y1 deletion, or selective antagonism with MRS2500, in oxidative
      venous thrombosis in mice. The P2Y12 antagonist, clopidogrel, was included as a
      reference agent. Anesthetized C57BL/6 or genetically modified mice underwent 3.5
      or 5 % FeCl(3)-induced vena cava thrombosis. Pharmacokinetic properties of
      MRS2500 were defined for dose selection. Platelet aggregation and renal or tail
      bleeding times (BT) were measured to put antithrombotic effects into perspective.
      P2Y1 deletion significantly reduced (p < 0.001) venous thrombus weight by 74 % in
      3.5 % FeCl(3) injury compared to P2Y1(+/+) littermates. MRS2500 (2 mg/kg, i.v.)
      significantly decreased (p < 0.001) thrombus weight 64 % in C57BL/6 mice. In the
      more severe 5 % FeCl(3)-induced injury model, thrombus weight significantly (p <
      0.001) decreased 68 % in P2Y1(-/-) mice versus P2Y1(+/+) mice, and MRS2500 (2
      mg/kg) was also beneficial (54 % decrease, p < 0.01). Renal BT doubled in P2Y1(-/
      ) versus P2Y1(+/+) mice, and increased threefold with MRS2500 compared to
      vehicle. Tail BT was markedly prolonged in P2Y1(-/-) mice (7.9X) and in C57BL/6
      mice given MRS2500. The current study demonstrates that P2Y1 deletion or
      antagonism significantly reduced venous thrombosis in mice, suggesting that P2Y1
      receptors play a role in the pathogenesis of venous thrombosis, at least in this
      species. However as with many antithrombotic agents the benefit comes at the
      potential price of an increase in provoked bleeding times.

PMID- 22588535
TI  - Mean platelet volume and D-dimer in patients with suspected deep venous
      thrombosis.
AB  - The aim of this retrospective study was to evaluate the diagnostic value of mean
      platelet volume (MPV) and D-dimer for acute deep venous thromboembolism (DVT).
      Two hundred and fifty six patients who presented to the emergency or
      cardiovascular surgery department with suspected lower limb DVT were
      retrospectively recruited. Plasma levels of MPV, platelet count, and D-dimer were
      obtained and duplex sonography examination was performed for all patients. Eighty
      four patients had acute DVT which was diagnosed by duplex ultrasonography. MPV
      was significantly higher in patients with DVT than in those without DVT (p <
      0.01). The mean MPV was 7.97 +/- 17.8 and 7.58 +/- 0.87 fL in patients with DVT
      and without DVT, respectively (p < 0.01). D-dimer was significantly higher in
      patients with DVT (p < 0.01). For all the patients, a positive MPV when the cut
      off value was 7.3 fL, had 69.7 % sensitivity and 43.9 % specificity. D-dimer
      (with a cut-off value of 0.5 MUg/mL) had 82.9 % sensitivity and 32.7 %
      specificity. In case of combination of MPV and D-dimer, the specificity exceeded
      (65.9 %) despite the reduction in sensitivity (59.2 %). Elevated MPV was found to
      be associated with acute DVT and high levels of MPV might increase the
      specificity of D-dimer for exclusion of DVT.

PMID- 22588536
TI  - The effect of lycopene treatment on ACE activity in rats with experimental
      diabetes.
AB  - In this study, the anti-inflammatory and antioxidant known as lycopene was
      applied to rats with experimental diabetes with the aim of investigating the
      detection of diabetes-related complications, and to determine the possible role
      of lycopene in diabetes complications regarding the effects of ACE activity. In
      order to induce diabetes in rats in the diabetes (D) and diabetes+lycopene (DL)
      groups, rats were given 45 mg/kg single-dose streptozotocin (STZ)
      intraperitoneally (i.p.); lycopene (10 mg/kg/day dissolved in sunflower oil) was
      administered to the rats in the lycopene-only (L) and DL groups. Blood glucose
      levels and HbA1c% in diabetes+lycopene group and diabetes group increased (p
      <0.05) compared to control and only lycopene treated group. The highest level of
      ACE activity was observed in the (D) group (p < 0.05). Activity in the (L) group
      was also significantly greater than in the control group (p < 0.05). The (DL)
      group had lower (p < 0.05). ACE activity than the (D) group. Lycopene
      implementation was found to be effective in the inhibition of ACE activity, an
      important indicator of diabetes-related complications.

PMID- 22588537
TI  - An electrically controlled quantum dot based spin current injector.
AB  - We present a proposal for a fully electrically controllable quantum dot based
      spin current injector. The device consists of a quantum dot that is strongly
      coupled to a ferromagnetic electrode on one side and weakly coupled to a
      nonmagnetic electrode on the other side. The presence of the ferromagnetic
      electrode results in an exchange field that splits the dot level. We show that
      this exchange-induced splitting can lead to almost full spin polarization of the
      current flowing through the device. Moreover, we also demonstrate that the sign
      of polarization can be changed by the gate or the bias voltage within a switching
      time in the nanosecond range. Thus, the proposed device can operate as an
      electrically controlled, rapidly switchable spin current source, which can be
      realized in various state-of-the-art nanostructures.

PMID- 22588538
TI  - Stanniocalcin supports the functional adaptation of adult-sized kidneys
      transplanted into the pediatric recipients.
AB  - BACKGROUND: The functional adaptation of adult-sized kidney (ASK) grafts to the
      recipient's size is not completely reversible and is associated with irreversible
      histologic damage in the smallest recipients. The aim of the study was to unveil
      the molecular mechanisms underlying the functional adaptation of ASK transplants
      to small pediatric recipients. METHODS: Because physiologic and functional
      adaption of ASK in infants is seen maximally at 3 months after transplantation,
      we selected 21 pediatric recipients of an ASK with protocol biopsies at
      engraftment and 3 and 6 months, without delayed graft function or interval
      rejection, and we conducted whole-genome expression profiles of the renal
      allograft biopsies at 3 months and correlated results with subsequent absolute
      glomerular filtration rate (aGFR). RESULTS: Seven hundred twenty-four unique
      genes correlated significantly with aGFR (q value <5%). Canonical pathway
      analysis identified overrepresentation of relevant pathways involved in
      regulation of tubular salt reabsorption and enzymatic pathways for organ
      development and hypertrophy. The single gene that correlated best with aGFR was
      stanniocalcin 1 (STC1). STC1 expression also correlated with the recipient's size
      at the time of transplantation and the chronic allograft damage index at 6
      months. CONCLUSIONS: Functional adaptation of adult-sized grafts to the pediatric
      recipient is associated with molecular adaptation for normal-volume homeostasis
      of the recipient. Our finding also suggests that stanniocalcin (STC1) plays an
      important role on functional adaption in pediatric kidney transplantation.

PMID- 22588539
TI  - Deletion of CD98 heavy chain in T cells results in cardiac allograft acceptance
      by increasing regulatory T cells.
AB  - BACKGROUND: Little is known about the CD98 heavy chain (CD98hc) in the T
      lymphocyte-mediated immune response to alloantigen. METHODS: We used an in vitro
      mixed leukocyte reaction assay and a cardiac transplantation model to evaluate
      the mechanisms of CD98hc in regulating alloimmune responses. RESULTS: A T cell
      specific deficiency of CD98hc resulted in lower responses to alloantigen
      stimulation in a mixed leukocyte reaction assay, and CD98hc-deficient mice
      accepted full major histocompatibility complex-mismatched cardiac allografts.
      Consistent with graft survival, the infiltration of the graft by immune cells in
      CD98hc-deficient mice was significantly lower than that in wild-type mice. A
      chemotaxis assay revealed the migration of CD98hc-deficient lymphocytes to
      decrease in the presence of CCL5 compared with wild-type cells. Moreover, the
      proportion of CD4/Foxp3-positive cells and Foxp3 messenger RNA increased
      significantly in CD98hc-deficient recipients, consistent with the down-regulation
      of mammalian target of rapamycin and PS6 kinase; and allograft permanent
      acceptance was shortened by the depletion of antibody-induced regulatory T cells.
      Finally, neutralizing antibody against CD98hc prolonged the cardiac allograft
      survival. CONCLUSIONS: Taken together, our data indicate that T cell-specific
      deficiency in CD98hc can contribute to cardiac allograft permanent acceptance
      correlating with the attenuation of lymphocyte migration and by increasing the
      generation of regulatory T cells. These findings are expected to make it possible
      to develop novel approaches for treating allograft rejection and promoting
      transplantation tolerance.

PMID- 22588541
TI  - Hydrolytically stable octahedral silicon complexes as bioactive scaffolds:
      application to the design of DNA intercalators.
AB  - We here introduce octahedral silicon serving as a structural center for the
      design of hydrolytically stable bioactive complexes as demonstrated with the
      generation of silicon-based high affinity DNA binders. This proof-of-principle
      study suggests that octahedral silicon complexes are falsely neglected, promising
      structural templates for widespread applications in chemical biology and
      medicinal chemistry.

PMID- 22588542
TI  - Mitral bioprosthetic valve stenosis in a patient with antiphospholipid antibody
      syndrome and systemic lupus erythematosus.
AB  - A 45-year-old woman with antiphospholipid antibody syndrome (APS) and systemic
      lupus erythematosus was admitted because of severe dyspnea. She had undergone
      mitral valve replacement (MVR) using a Mosaic bioprosthesis for infective
      endocarditis 9 years previously. She developed congestive heart failure secondary
      to mitral bioprosthetic valve stenosis resulting from relatively early structural
      valve deterioration. She underwent a second MVR using a mechanical valve
      prosthesis. The explanted bioprosthesis showed marked pannus formation and
      mineralization with fibrin thrombus formation, especially on the outflow surfaces
      of the leaflets. After the second operation, she was discharged without APS
      related thromboembolic events under meticulous anticoagulant and antiplatelet
      therapies.

PMID- 22588543
TI  - The role of Nogo-A in axonal plasticity, regrowth and repair.
AB  - Axonal damage leads to permanent deficits in the adult central nervous system
      (CNS) not only because of the weak intrinsic ability of adult neurons to activate
      their growth program but importantly also because of the presence of specific
      growth inhibitors in the CNS tissue and the environment of the damaged axons. The
      well-studied myelin-derived protein Nogo-A is involved in various cellular and
      molecular events contributing to the failure of CNS axons to regrow and reconnect
      after transection. Recent studies have shown that, by acting in a negative way on
      the cytoskeleton and on the growth program of axotomized neurons, Nogo-A exerts
      fast and chronic inhibitory effects on neurite outgrowth. On the other hand, the
      blockade of Nogo-A results in a marked enhancement of compensatory and
      regenerative axonal extension in vivo; this enhancement is often paralleled by
      significant functional recovery, for example, of locomotion or skilled forelimb
      reaching after spinal cord or stroke lesions in rats and monkeys. Surprisingly,
      the blockade of Nogo-A or its receptor NgR in the hippocampus has recently been
      demonstrated to enhance long-term potentiation. A role of Nogo-A in synaptic
      plasticity/stability might therefore represent an additional, new and important
      aspect of CNS circuit remodeling. Function-blocking anti-Nogo-A antibodies are
      currently being tested in a clinical trial for improved outcome after spinal cord
      injury.

PMID- 22588545
TI  - Spectrum of cutaneous and soft tissue lesions in two Carney complex patients
      adnexal induction versus authentic adnexal neoplasms.
AB  - Two unusual Carney complex patients are described. In one of them, several
      cutaneous biopsies revealed myxoid lesions that were rather more close to
      authentic adnexal neoplasms with myxoid stroma than to a "myxoma with an
      epithelial component." These included lesions resembling trichofolliculoma,
      infundibular cyst, and trichodiscoma. Additionally, 1 soft tissue myxoma was
      unique in the sense that it greatly resembled a cardiac myxoma, begging the
      question whether this could represent an embolus from the patient's cardiac
      myxoma. Given the large size and complexity and heterogeneity of the cutaneous
      lesions, the authors suggest that these may represent authentic cutaneous
      neoplasms accompanied by myxoid stroma and not adnexal elements induced by the
      stroma. However, the latter mechanism is well recognized and demonstrated by our
      second patient in whom adnexal-type elements in the cutaneous lesion were clearly
      induced by the myxoid stroma but were unusually complex by manifesting
      panfollicular and also sebaceous differentiation.

PMID- 22588546
TI  - Malignant melanoma within squamous cell carcinoma and basal cell carcinoma: is it
      a combined or collision tumor?--a case report and review of the literature.
AB  - We report a case of a very unusual combined and collision basosquamous
      melanocytic malignant tumor on the chest of an 84-year-old man. To our knowledge,
      this is the first case report describing this entity. We attempt to address the
      diagnostic challenge and the clinical and histological characteristics of these
      rare neoplasms with a review of the English literature to further categorize and
      summarize what has been previously reported about these extraordinary tumors.

PMID- 22588547
TI  - Clonal identity and differences in primary cutaneous B-cell lymphoma occurring at
      different sites or time points in the same patient.
AB  - Primary cutaneous B-cell lymphomas (PCBCL) are rare. Marginal zone lymphomas and
      follicle center lymphomas (FCL) represent a majority of these cases, and a
      significant number of cases present with multiple lesions. It is unclear whether
      multiple lesions in PCBCL represent dissemination of a single clone or multiple
      new primary lymphomas. In the current study, we analyzed paired samples from 20
      PCBCL patients at more than 1 site (16) or at the same site at different time
      points (4) and 12 patients with benign lymphoid infiltrates to investigate for
      the presence or absence of a clone, and if present, whether the clones were
      identical. Both IGH@ and IGK@ rearrangements were tested using the BIOMED-2
      protocol. We identified a clone (IGH@ and/or IGK@) in 19 of 20 (95%) PCBCL
      patients and 2 of 12 (17%) benign lymphoid infiltrate patients. The B-cell clones
      were proven to be identical in 11 of 20 (55%) PCBCL patients, including 7 of
      16(44%) biopsies from patients with 2 different sites and 4 of 4 biopsies (100%)
      from patients at the same site but different time points. In 4 cases (3 FCL and 1
      marginal zone lymphoma), different clones were detected at different sites,
      suggesting the possibility of a second simultaneous primary lymphoma. Our results
      indicate that the presence of identical clones is highly suggestive of lymphoma.
      To our knowledge, this is the first report to investigate the detection of
      identical clones in 2 distinct biopsies in PCBCL patients. Although the study is
      small and the results need to be confirmed in a larger study, these findings
      suggest that a subset of PCBCL at different sites may represent different primary
      tumors rather than occurrence of a single disease.

PMID- 22588548
TI  - A clinicopathologic and molecular biologic study of patients presenting with few
      adnexal tumors (two to four) from the morphological spectrum of Brooke-Spiegler
      syndrome.
AB  - We report 11 individuals, each presenting with few (2-4) adnexal neoplasms
      histologically confirmed as belonging to the spectrum of lesions typical for
      Brooke-Spiegler syndrome (BSS) and/or multiple familial trichoepitheliomas. These
      include spiradenoma, cylindroma, spiradenocylindroma, and trichoblastoma
      variants. Our objective was to clarify whether this is merely a sporadic, albeit
      unusual, occurrence of multiple neoplasms in these patients or whether they are
      related to BSS and its phenotypic variant, multiple familial trichoepithelioma.
      Six patients presented with 2 neoplasms, 4 had 3 lesions and the last had 4
      lesions. In none was there any family history of similar lesions. The 28
      neoplasms consisted of 7 spiradenomas, 6 cylindromas, 5 spiradenocylindromas, and
      11 trichoblastomas (6 trichoepitheliomas and 5 with mixed patterns). In 1 patient
      only with 2 spiradenomas, both tumors harbored identical CYLD sequence
      alterations (c.1112C>A/S371X) in the CYLD gene and both showed loss of
      heterozygosity on chromosome 16q. The remaining cases yielded neither germ line
      nor somatic alterations in CYLD. It is concluded that the presentation with few
      (2-4) cylindromas, spiradenomas, spiradenocylindromas, and trichoepitheliomas is
      a sporadic occurrence, and that these patients do not have any relationship to
      BSS.

PMID- 22588549
TI  - Pseudotumoral cutaneous aspergillosis in chronic granulomatous disease, report of
      a pediatric case.
AB  - Invasive aspergillosis is a life-threatening condition in patients with chronic
      granulomatous disease (CGD). Skin invasion by Aspergillus occurs most commonly by
      contiguity to a neighboring cavity. We describe an unusual case of invasive
      cutaneous aspergillosis presented as a large burgeoning tumor in a 4-year-old
      girl with CGD who underwent surgical treatment for bifocal osteomyelitis of the
      left leg. The skin invasion occurred 4 months after a "successful" treatment of
      invasive pulmonary aspergillosis. Atypical presentation and diagnostic
      difficulties are discussed. Invasive cutaneous aspergillosis may be polymorphic.
      The diagnosis should be considered early in the etiological investigation of any
      suspicious skin lesions in CGD even in uncommon aspects such as burgeoning
      tumors.

PMID- 22588551
TI  - Maternal intimate partner violence victimization and under-five children
      mortality in Western Ethiopia: a case-control study.
AB  - OBJECTIVE: This study aimed to compare the association between maternal intimate
      partner violence and under-five mortality. METHODS: Matched case-control study
      was conducted from May to June 2011. A sample of 286 cases and 572 controls were
      randomly selected from East Wollega Zone, West Ethiopia. RESULTS: Among cases,
      72.7% ever experienced controlling behaviors when compared to 62.4% for controls.
      All forms of maternal intimate partner violence were experienced by 61.9% of
      cases and 50.9% of controls. Controlling behavior in marriage and experiences of
      all forms of intimate partner violence during lifetime were more than four
      [adjusted odds ratio (AOR) 4.27, 95% confidence interval (CI) 0.97-18.89), and
      two (AOR = 2.55, 95% CI 1.66-3.92) times as likely to be associated with under
      five mortality. CONCLUSION: Maternal intimate partner violence victimization is
      strongly associated with under-five mortality. Involving men in maternal and
      child health programs could be one strategy to address the issue of intimate
      partner violence against women.

PMID- 22588552
TI  - Urine flow cytometry as a primary screening method to exclude urinary tract
      infections.
AB  - PURPOSE: To exclude urinary tract infections, culture is the gold standard
      method, although it is time consuming and costly. Current strategies using
      dipstick analysis are unsatisfactory as screening methods, because of inadequate
      sensitivity/specificity. Urine flow cytometry is an attractive alternative. To
      exclude urinary tract infections, a cutoff value to screen for negative cultures
      was determined. METHODS: 281 outpatients (51 % male) of a general population
      visiting the urology department were included. Urine samples were measured by
      flow cytometry and compared with culture results and dipstick analysis. ROC
      analysis was performed to evaluate the screening performance of flow cytometry
      and dipstick analysis compared to culture. RESULTS: 18 % of cultures were
      positive, defined as >10(4) colony forming units/mL. Bacterial count by flow
      cytometry alone provides the best sensitivity and specificity to exclude a
      urinary tract infection. A cutoff value of 60 bacteria/MUL urine leads to a
      sensitivity of 100 % and a specificity of 60 %. Retrospectively, with a cutoff
      value of 60 bacteria/MUL urine, 49 % of the cultures would have been redundant.
      20 % of patients receiving antibiotics possibly had received those unnecessarily.
      The calculated percentage of false negatives was 0 % (95 % confidence interval 0
      3.3 %). CONCLUSIONS: Urine flow cytometry is a reliable screening method to
      exclude urinary tract infections. With a cutoff value of 60 bacteria/MUL urine,
      negative predictive value is 100 % and the calculated percentage of false
      negatives is 0 % (95 % confidence interval 0-3.3 %). Using flow cytometry as a
      screening method could lead to a reduction in cultures and antibiotics.

PMID- 22588555
TI  - Clusterin inhibition using OGX-011 synergistically enhances antitumour activity
      of sorafenib in a human renal cell carcinoma model.
AB  - BACKGROUND: The objective of this study was to investigate whether the
      therapeutic activity of sorafenib could be enhanced by combining with OGX-011, an
      antisense oligodeoxynucleotide (ODN) targeting clusterin, in renal cell carcinoma
      (RCC). METHODS: We investigated the effects of combined treatment with OGX-011
      and sorafenib on a human RCC ACHN model both in vitro and in vivo. RESULTS:
      Although clusterin expression was increased by sorafenib, additional treatment of
      ACHN with OGX-011 significantly blocked the upregulation of clusterin induced by
      sorafenib. Despite the lack of a significant effect on the growth of ACHN, OGX
      011 synergistically enhanced the sensitivity to sorafenib, reducing the IC(50) by
      >50%. Apoptotic changes were intensively detected in ACHN after combined
      treatment with OGX-011 and a sublethal dose of sorafenib, but not either agent
      alone. Furthermore, this combined treatment resulted in the marked downregulation
      of phosphorylated Akt and p44/42 mitogen-activated protein kinase in ACHN
      compared with treatment with either agent alone. In vivo systemic administration
      of OGX-011 plus sorafenib significantly decreased the ACHN tumour volume compared
      with control ODN plus sorafenib. CONCLUSION: Combined use with OGX-011 may be
      useful in enhancing the cytotoxic effect of sorafenib on RCC by inducing
      apoptosis and inactivating major signal transduction pathways.

PMID- 22588556
TI  - Risk of liver cancer among US male veterans with cirrhosis, 1969-1996.
AB  - BACKGROUND: Liver cancer incidence rates in the United States have increased for
      several decades for reasons that are not entirely clear. Regardless of aetiology,
      cirrhosis is a strong risk factor for liver cancer. As mortality from cirrhosis
      has been declining in recent decades, it is possible that the risk of liver
      cancer among persons with cirrhosis has been affected. METHODS: Data from the US
      Veterans Affairs medical records database were analysed after adjustment for
      attained age, race, number of hospital visits, obesity, diabetes, and chronic
      obstructive pulmonary disease. Hazard ratio (HR) and 95% confidence interval (95%
      CI) were calculated using Cox proportional hazards modelling. Survival analyses
      were conducted using age as the time metric and incidence of cirrhosis as a time
      dependent covariate. RESULTS: Among 103 257 men with incident cirrhosis, 788
      liver cancers developed. The HR of liver cancer was highest among men with viral
      related cirrhosis (HR=37.59, 95% CI: 22.57-62.61), lowest among men with alcohol
      related cirrhosis (HR=8.20, 95% CI: 7.55-8.91) and intermediate among men with
      idiopathic cirrhosis (HR=10.45, 95% CI: 8.52-12.81), when compared with those
      without cirrhosis. Regardless of cirrhosis type, white men had higher HRs than
      black men. The HR of developing liver cancer increased from 6.40 (95% CI: 4.40
      9.33) in 1969-1973 to 34.71 (95% CI: 23.10-52.16) in 1992-1996 for those with
      cirrhosis compared with those without. CONCLUSION: In conclusion, the
      significantly increased HR of developing liver cancer among men with cirrhosis
      compared with men without cirrhosis in the United States may be contributing to
      the increasing incidence of liver cancer.

PMID- 22588557
TI  - A novel oncogenic pathway by TLS-CHOP involving repression of MDA-7/IL-24
      expression.
AB  - BACKGROUND: Translocated in liposarcoma-CCAAT/enhancer binding protein homologous
      protein (TLS-CHOP) (also known as FUS-DDIT3) chimeric oncoprotein is found in the
      majority of human myxoid liposarcoma (MLS), but its molecular function remains
      unclear. METHODS: We knockdowned TLS-CHOP expression in MLS-derived cell lines by
      a specific small interfering RNA, and analysed the gene expression profiles with
      microarray. RESULTS: TLS-CHOP knockdown inhibited growth of MLS cells, and
      induced an anticancer cytokine, melanoma differentiation-associated gene 7 (MDA
      7)/interleukin-24 (IL-24) expression. However, double knockdown of TLS-CHOP and
      MDA-7/IL-24 did not inhibit MLS cell growth. CONCLUSION: Repression of MDA-7/IL
      24 expression by TLS-CHOP is required for MLS tumour growth, and TLS-CHOP may
      become a promising therapeutic target for MLS treatment.

PMID- 22588558
TI  - c-Myc and EBV-LMP1: two opposing regulators of the HLA class I antigen
      presentation machinery in epithelial cells.
AB  - BACKGROUND: Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) up
      regulates the human leukocyte antigen (HLA) class I antigen presentation
      machinery (APM). This appears counterintuitive with immune evasion in EBV
      associated tumours like nasopharyngeal carcinoma (NPC). METHODS: Latent membrane
      protein 1-transfected epithelial cell lines were used as a model system to study
      the impact of LMP1 and c-Myc on HLA class I components. The expression of
      components of the HLA class I APM, c-Myc and Ki-67 was analysed in LMP1+ and LMP1
      NPC by immunohistochemistry. RESULTS: In epithelial cells, LMP1 up-regulated HLA
      class I APM. This effect could be counteracted by c-Myc, which itself was up
      regulated by LMP1 apparently through IL6 induction and Jak3/STAT3 activation.
      Studies of NPC biopsies revealed down-regulation of HLA class I APM expression.
      No difference was observed between LMP1+ and LMP1- NPC. However, expression of Ki
      67 and c-Myc were up-regulated in LMP1+ tumours. CONCLUSION: These findings raise
      the possibility that c-Myc activation in NPC might antagonise the effect of LMP1
      on HLA class I expression thus contributing to immune escape of tumour cells.

PMID- 22588559
TI  - The relationship between vitamin D and chemotherapy-induced toxicity - a pilot
      study.
AB  - BACKGROUND: There are anecdotal data that lower levels of vitamin D may be
      associated with increased levels of toxicity in individuals receiving
      chemotherapy; we therefore wished to investigate this further. METHODS: From a
      cohort of over 11 000 individuals, we included those who had vitamin D levels
      (serum 1,25(OH)(2)D3) measured before and during chemotherapy. They were analysed
      for side effects correlating Chemotherapy Toxicity Criteria with vitamin D
      levels, normalising data for general markers of patient health including C
      reactive protein and albumin. RESULTS: A total of 241 (2% of the total cohort)
      individuals entered the toxicity analysis. We found no overall difference in
      toxicity effects experienced by patients depending on whether they were vitamin D
      depleted or had sufficient levels (P=0.78). CONCLUSION: This pilot study suggests
      routine vitamin D measurement during treatment does not appear to be necessary in
      the management of chemotherapy-induced toxicity.

PMID- 22588560
TI  - Long-term results of screening with magnetic resonance imaging in women with BRCA
      mutations.
AB  - BACKGROUND: The addition of breast magnetic resonance imaging (MRI) to screening
      mammography for women with BRCA mutations significantly increases sensitivity,
      but there is little data on clinical outcomes. We report screening performance,
      cancer stage, distant recurrence rate, and breast cancer-specific mortality in
      our screening study. METHODS: From 1997 to 2009, 496 women aged 25 to 65 years
      with a known BRCA1/2 mutation, of whom 380 had no previous cancer history, were
      enrolled in a prospective screening trial that included annual MRI and
      mammography. RESULTS: In 1847 screening rounds, 57 cancers were identified (53
      screen-detected, 1 interval, and 3 incidental at prophylactic mastectomy), of
      which 37 (65%) were invasive. Sensitivity of MRI vs mammography was 86% vs 19%
      over the entire study period (P<0.0001), but was 74% vs 35% from 1997 to 2002
      (P=0.02) and 94% vs 9% from 2003 to 2009 (P<0.0001), respectively. The relative
      sensitivities of MRI and mammography did not differ by mutation, age, or invasive
      vs non-invasive disease. Of the incident cancers, 97% were Stage 0 or 1. Of 28
      previously unaffected women diagnosed with invasive cancer, 1 BRCA1 mutation
      carrier died following relapse of a 3 cm, node-positive breast cancer diagnosed
      on her first screen at age 48 (annual breast cancer mortality rate=0.5%). Three
      patients died of other causes. None of the 24 survivors has had a distant
      recurrence at a median follow-up of 8.4 years since diagnosis. CONCLUSION:
      Magnetic resonance imaging surveillance of women with BRCA1/2 mutations will
      detect the majority of breast cancers at a very early stage. The absence of
      distant recurrences of incident cancers to date is encouraging. However, longer
      follow-up is needed to confirm the safety of breast surveillance.

PMID- 22588561
TI  - [Legal probation after deferred retrospective preventive detention: implications
      for the amended regulations on preventive detention].
AB  - The study examines the legal probation of offenders who are considered to be
      highly dangerous but due to the decision of the Federal High Court were not in
      retrospective preventive detention (S 66b StGB). In view of the current
      discussion, in anticipation of a detailed presentation of the study results the
      relevant criteria "probation behavior", "personality characteristics" and
      "prognosis quality" are picked out. The results are evaluated with respect to
      knowledge of the restrictions conditioned by the study regarding the usefulness
      for the prognosis of reoffending. The results of this study suggest that it might
      be useful to describe psychological criteria for the not seriously reoffending
      group of probands.

PMID- 22588562
TI  - [HTLV-1-associated myelopathy/tropical spastic paraparesis: a differential
      diagnosis in multiple sclerosis].
AB  - Human T-cell lymphotropic virus 1 (HTLV-1) associated myelopathy/tropical spastic
      paraparesis (HAM/TSP) is a neurological disease caused by infection with HTLV-1.
      The disorder is very rare in Europe but endemic in many parts of the world. The
      pathogenesis is not clearly characterized but is based on a possibly immune
      mediated injury of the cervicothoracic spinal cord. Clinically, HAM/TSP
      constitutes a slowly progressive spastic paraparesis associated with bladder
      dysfunction and often mimics the course of autoimmune and neurodegenerative
      diseases. The diagnosis is based on typical symptoms as well as detection of HTLV
      1 specific antibodies and proviral HTLV-1 DNA or HTLV-1 RNA. The therapy is
      limited to symptomatic treatment. Transmission of HTLV-1 can occur vertically by
      breast feeding, through sexual contact or via infected blood products. Based on a
      clinical case report, we present here a current review on the pathophysiology,
      epidemiology, clinical manifestations, diagnosis and treatment of HAM/TSP.

PMID- 22588563
TI  - Amino acid-assimilating phototrophic heliobacteria from soda lake environments:
      Heliorestis acidaminivorans sp. nov. and 'Candidatus Heliomonas lunata'.
AB  - Two novel taxa of heliobacteria, Heliorestis acidaminivorans sp. nov. strain
      HR10B(T) and 'Candidatus Heliomonas lunata' strain SLH, were cultured from
      shoreline sediments/soil of Lake El Hamra (Egypt) and lake water/benthic
      sediments of Soap Lake (USA), respectively; both are highly alkaline soda lakes.
      Cells of strain HR10B were straight rods, while cells of strain SLH were curved
      rods. Both organisms were obligate anaerobes, produced bacteriochlorophyll g, and
      lacked intracytoplasmic photosynthetic membrane systems. Although the absorption
      spectrum of strain HR10B was typical of other heliobacteria, that of strain SLH
      showed unusually strong absorbance of the OH-chlorophyll a component. Major
      carotenoids of both organisms were OH-diaponeurosporene glucosyl esters, as in
      other alkaliphilic heliobacteria, and both displayed an alkaliphilic and
      mesophilic phenotype. Strain HR10B was remarkable among heliobacteria in its
      capacity to photoassimilate a number of carbon sources, including several amino
      acids. Nitrogenase activity was observed in strain HR10B, but not in strain SLH.
      The 16S ribosomal RNA gene tree placed strain HR10B within the genus Heliorestis,
      but distinct from other described species. By contrast, strain SLH was
      phylogenetically more closely related to neutrophilic heliobacteria and is the
      first alkaliphilic heliobacterium known outside of the genus Heliorestis.

PMID- 22588564
TI  - Synthesis of novel E-2-chlorovinyltellurium compounds based on the stereospecific
      anti-addition of tellurium tetrachloride to acetylene.
AB  - The reaction of tellurium tetrachloride with acetylene proceeds in a
      stereospecific anti-addition manner to afford the novel products E-2
      chlorovinyltellurium trichloride and E,E-bis(2-chlorovinyl)tellurium dichloride.
      Reaction conditions for the selective preparation of each of these products were
      found. The latter was obtained in 90% yield in CHCl(3) under a pressure of
      acetylene of 10-15 atm, whereas the former product was formed in up to 72% yield
      in CCl(4) under a pressure of acetylene of 1-3 atm. Synthesis of the previously
      unknown E,E-bis(2-chlorovinyl) telluride, E,E-bis(2-chlorovinyl) ditelluride, E-2
      chlorovinyl 1,2,2-trichloroethyl telluride and E,E-bis(2-chlorovinyl)-tellurium
      dibromide is described.

PMID- 22588565
TI  - The pedagogical ebb and flow of human patient simulation: empowering through a
      process of fading support.
AB  - The use of the high-fidelity human patient simulator (HPS)-based clinical
      scenario in undergraduate nursing education is a powerful learning tool, well
      suited to modern nursing students' preference for immersive construction of
      knowledge through the provision of contextually rich reality-based practice and
      social discourse. The purpose of this study was to explore the social
      psychological processes that occur within HPS-based clinical scenarios. Grounded
      theory method was used to study students and faculty sampled from a Western
      Canadian baccalaureate nursing program. The process of leveled coding generated a
      substantive theory that has the potential to enable educators to empower students
      through the use of fading support, a twofold process composed of adaptive
      scaffolding and dynamic assessment that challenges students to realistically self
      regulate and transform their frame of reference for nursing practice, while
      limiting the threats that traditional HPS-based curriculum can impose.

PMID- 22588566
TI  - National survey of RN-to-BSN programs.
AB  - More than 600 RN-to-BSN programs exist in the United States. Little information
      is available describing many aspects of these programs (e.g., curricula, program
      length, prerequisites). This study was undertaken to obtain a snapshot of RN-to
      BSN education. This review is vital given the rapid growth of these programs and
      the anticipated increase in number of "completion" students necessary to meet the
      Institute of Medicine's goal that 80% of RNs be BSN-prepared by 2020. Data were
      collected and analyzed within general areas, including background information,
      curriculum, instructional formats, and evaluation. Findings from the survey can
      be used by educators to evaluate their RN-to-BSN programs and compare them with
      other programs. Further, evidence of potential weaknesses were identified, and
      educators are challenged to ensure that encouraging growth, focusing on
      flexibility, and making programs more user friendly does not result in inferior
      education. Rather, academic and programmatic rigor must be maintained.

PMID- 22588567
TI  - Job stress, mentoring, psychological empowerment, and job satisfaction among
      nursing faculty.
AB  - The National League for Nursing endorses mentoring throughout nursing faculty's
      careers as the method to recruit nurses into academia and improve retention of
      nursing faculty within the academy. A nationwide sample of 959 full-time nursing
      faculty completed a descriptive survey comprising a researcher-created
      demographic questionnaire plus Dreher's mentoring scale, Gmelch's faculty stress
      index, Spreitzer's psychological empowerment scale, and the National Survey for
      Postsecondary Faculty's job satisfaction scale. Results showed that 40% of the
      sample had a current work mentor. Variables showed significant relationships to
      job satisfaction (p < 0.01): mentoring quality (0.229), job stress (-0.568), and
      psychological empowerment (0.482). Multiple regression results indicated job
      satisfaction was significantly influenced (p < 0.01) by the presence of a
      mentoring relationship, salary, tenure status, psychological empowerment, and job
      stress. The regression model explained 47% of the variance in job satisfaction
      for the sample.

PMID- 22588568
TI  - High pseudocapacitive cobalt carbonate hydroxide films derived from CoAl layered
      double hydroxides.
AB  - A thin nanosheet of mesoporous cobalt carbonate hydroxide (MPCCH) has been
      fabricated from a CoAl-LDH nanosheet following removal of the Al cations by
      alkali etching. The basic etched electrode exhibits enhanced specific capacitance
      (1075 F g(-1) at 5 mA cm(-2)) and higher rate capability and cycling stability
      (92% maintained after 2000 cycles).

PMID- 22588569
TI  - Interspecific comparison of constitutive ash phloem phenolic chemistry reveals
      compounds unique to manchurian ash, a species resistant to emerald ash borer.
AB  - The emerald ash borer (Agrilus planipennis, EAB) is an invasive wood-borer
      indigenous to Asia and is responsible for widespread ash (Fraxinus spp.)
      mortality in the U.S. and Canada. Resistance and susceptibility to EAB varies
      among Fraxinus spp., which is a result of their co-evolutionary history with the
      pest. We characterized constitutive phenolic profiles and lignin levels in the
      phloem of green, white, black, blue, European, and Manchurian ash. Phloem was
      sampled twice during the growing season, coinciding with phenology of early and
      late instar EAB. We identified 66 metabolites that displayed a pattern of
      variation, which corresponded strongly with phylogeny. Previously identified
      lignans and lignan derivatives were confirmed to be unique to Manchurian ash, and
      may contribute to its high level of resistance to EAB. Other compounds that had
      been considered unique to Manchurian ash, including hydroxycoumarins and the
      phenylethanoids calceolarioside A and B, were detected in closely related, but
      susceptible species, and thus are unlikely to contribute to EAB resistance of
      Manchurian ash. The distinct phenolic profile of blue ash may contribute to its
      relatively high resistance to EAB.

PMID- 22588570
TI  - Insect egg deposition induces indirect defense and epicuticular wax changes in
      Arabidopsis thaliana.
AB  - Egg deposition by the Large Cabbage White butterfly Pieris brassicae on Brussels
      sprouts plants induces indirect defense by changing the leaf surface, which
      arrests the egg parasitoid Trichogramma brassicae. Previous studies revealed that
      this indirect defense response is elicited by benzyl cyanide (BC), which is
      present in the female accessory reproductive gland (ARG) secretion and is
      released to the leaf during egg deposition. Here, we aimed (1) to elucidate
      whether P. brassicae eggs induce parasitoid-arresting leaf surface changes in
      another Brassicacean plant, i.e., Arabidopsis thaliana, and, if so, (2) to
      chemically characterize the egg-induced leaf surface changes. Egg deposition by
      P. brassicae on A. thaliana leaves had similar effects to egg deposition on
      Brussels sprouts with respect to the following: (a) Egg deposition induced leaf
      surface changes that arrested T. brassicae egg parasitoids. (b) Application of
      ARG secretion of mated female butterflies or of BC to leaves had the same
      inductive effects as egg deposition. Based on these results, we conducted GC-MS
      analysis of leaf surface compounds from egg- or ARG-induced A. thaliana leaves.
      We found significant quantitative differences in epicuticular waxes compared to
      control leaves. A discriminant analysis separated surface extracts of egg-laden,
      ARG-treated, untreated control and Ringer solution-treated control leaves
      according to their quantitative chemical composition. Quantities of the fatty
      acid tetratriacontanoic acid (C34) were significantly higher in extracts of leaf
      surfaces arresting the parasitoids (egg-laden or ARG-treated) than in respective
      controls. In contrast, the level of tetracosanoic acid (C24) was lower in
      extracts of egg-laden leaves compared to controls. Our study shows that insect
      egg deposition on a plant can significantly affect the quantitative leaf
      epicuticular wax composition. The ecological relevance of this finding is
      discussed with respect to its impact on the behavior of egg parasitoids.

PMID- 22588572
TI  - Trends in the reproductive performance of Holstein dairy cows in Iran.
AB  - The study was undertaken to determine the trends in the reproductive performance
      of Holstein dairy cows in Iran during 1994 to 2008. Reproductive performance data
      for 528,034 lactations of 246,132 cows in 1,822 Holstein dairy herds of Iran were
      used. The potential effect of calving season, herd, parity, calving year, as well
      as herd size and 305-day milk production on reproductive performance traits was
      investigated using multiple regression models. The least squares means of age at
      first calving decreased by 3.1 (+/- 0.06) days per year from 806.5 (+/- 96.3)
      days in 1994 to 788 (+/- 89.9) days in 2008. The least squares means of calving
      interval increased 1.02 (+/- 0.03) days per year from 394.1 (+/- 65) days in 1994
      to 413.2 (+/- 81) days in 2008. Greater 305-day milk production was associated
      with an average increase of 6.55 (+/- 0.08) days in calving interval per 1,000-kg
      increase in milk yield. Larger herd size was associated with an average decrease
      of 0.22 (+/- 0.02) days in calving interval per 50 cows per herd. The mean number
      of days dry was 88.6 (+/- 51.3) days and increased by 0.82 (+/- 0.02) days per
      year. In conclusion, reproductive performance in Holstein dairy herds has
      generally decreased, whereas herd size and milk production have increased over
      time. Producers may make significant improvements in herd reproduction by
      reviewing management strategies including the sire selection, reproductive
      management, inseminator training and techniques, and improved estrous detection.
      Moreover, it may be advisable for the fertility traits to be included in the
      genetic selection indices to reduce the rate of reproductive decline.

PMID- 22588571
TI  - Molecular characterization of Streptococcus agalactiae and Streptococcus uberis
      isolates from bovine milk.
AB  - Streptococci are one among the major mastitis pathogens which have a considerable
      impact on cow health, milk quality, and productivity. The aim of the present
      study was to investigate the occurrence and virulence characteristics of
      streptococci from bovine milk and to assess the molecular epidemiology and
      population structure of the Indian isolates using multilocus sequence typing
      (MLST) and pulsed-field gel electrophoresis (PFGE). Out of a total of 209 bovine
      composite milk samples screened from four herds (A-D), 30 Streptococcus spp. were
      isolated from 29 milk samples. Among the 30 isolates, species-specific PCR and
      partial 16S rRNA gene sequence analysis identified 17 Streptococcus agalactiae
      arising from herd A and 13 Streptococcus uberis comprising of 5, 7, and 1
      isolates from herds B, C, and D respectively. PCR based screening for virulence
      genes revealed the presence of the cfb and the pavA genes in 17 and 1 S.
      agalactiae isolates, respectively. Similarly, in S. uberis isolates, cfu gene was
      present in six isolates from herd C, the pau A/skc gene in all the isolates from
      herds B, C, and D, whereas the sua gene was present in four isolates from herd B
      and the only isolate from herd D. On MLST analysis, all the S. agalactiae
      isolates were found to be of a novel sequence type (ST), ST-483, reported for the
      first time and is a single locus variant of the predicted subgroup founder ST
      310, while the S. uberis isolates were found to be of three novel sequence types,
      namely ST-439, ST-474, and ST-475, all reported for the first time. ST-474 was a
      double locus variant of three different STs of global clonal complex ST-143
      considered to be associated with clinical and subclinical mastitis, but ST-439
      and ST-475 were singletons. Unique sequence types identified for both S.
      agalactiae and S. uberis were found to be herd specific. On PFGE analysis,
      identical or closely related restriction patterns for S. agalactiae ST-483 and S.
      uberis ST-439 in herds A and B respectively, but an unrelated restriction pattern
      for S. uberis ST-474 and ST-475 isolates from herds D and C respectively, were
      obtained. This signifies that the isolates of particular ST may exhibit related
      PFGE patterns suggesting detection of a faster molecular clock by PFGE than MLST.
      Since all the isolates of both the species belonged to novel sequence types,
      their epidemiological significance in global context could not be ascertained,
      however, evidence suggests that they have uniquely evolved in Indian conditions.
      Further research would be useful for understanding the role of these pathogens in
      bovine sub-clinical mastitis and implementing effective control strategies in
      India.

PMID- 22588573
TI  - Intention-based EMG control for powered exoskeletons.
AB  - Electromyographical (EMG) signals have been frequently used to estimate human
      muscular torques. In the field of human-assistive robotics, these methods provide
      valuable information to provide effectively support to the user. However, their
      usability is strongly limited by the necessity of complex user-dependent and
      session-dependent calibration procedures, which confine their use to the
      laboratory environment. Nonetheless, an accurate estimate of muscle torque could
      be unnecessary to provide effective movement assistance to users. The natural
      ability of human central nervous system of adapting to external disturbances
      could compensate for a lower accuracy of the torque provided by the robot and
      maintain the movement accuracy unaltered, while the effort is reduced. In order
      to explore this possibility, in this paper we study the reaction of ten healthy
      subjects to the assistance provided through a proportional EMG control applied by
      an elbow powered exoskeleton. This system gives only a rough estimate of the user
      muscular torque but does not require any specific calibration. Experimental
      results clearly show that subjects adapt almost instantaneously to the assistance
      provided by the robot and can reduce their effort while keeping full control of
      the movement under different dynamic conditions (i.e., no alterations of movement
      accuracy are observed).

PMID- 22588574
TI  - Automated fiducial localization in CT images based on surface processing and
      geometrical prior knowledge for radiotherapy applications.
AB  - We propose a novel method for radio-opaque external marker localization in CT
      scans for infrared (IR) patient set-up in radiotherapy. Efforts were focused on
      the quantification of uncertainties in marker localization in the CT dataset as a
      function of algorithm performance. We implemented a 3-D approach to fiducial
      localization based on surface extraction and marker recognition according to
      geometrical prior knowledge. The algorithm parameters were optimized on a
      clinical CT dataset coming from 35 cranial and extra-cranial patients; the
      localization accuracy was benchmarked at variable image resolution versus laser
      tracker measurements. The applicability of conventional IR optical tracking
      systems for localizing external surrogates in daily patient set-up procedures was
      also investigated in 121 proton therapy treatment sessions. Our study shows that
      the implemented algorithm features surrogates localization with uncertainties
      lower than 0.3 mm and with a true positive rate of 90.1%, being this latter
      mainly influenced by fiducial homogeneity in the CT images. The reported clinical
      validation in proton therapy confirmed the submillimetric accuracy and the
      expected algorithm sensitivity. Geometrical prior knowledge allows judging the
      reliability of the extracted fiducial coordinates, ensuring the highest accuracy
      in patient set-up.

PMID- 22588576
TI  - A new approach to construct a fused 2-ylidene chromene ring: highly
      regioselective synthesis of novel chromeno quinoxalines.
AB  - Regioselective construction of a fused 2-ylidene chromene ring was achieved for
      the first time by using AlCl(3)-induced C-C bond formation followed by Pd/C-Cu
      mediate coupling-cyclization strategy. A number of chromeno[4,3-b]quinoxaline
      derivatives were prepared by using this strategy. Single crystal X-ray
      diffraction study of a representative compound e.g. 6-(2,2-dimethylpropylidene)-4
      methyl-6H-chromeno[4,3-b]quinoxalin-3-ol confirmed the presence of an exocyclic C
      C double bond with Z-geometry. The crystal structure analysis and hydrogen
      bonding patterns of the same compound along with its structure elaboration via
      propargylation followed by Sonogashira coupling of the resulting terminal alkyne
      is presented. A probable mechanism for the formation of 2-ylidene chromene ring
      is discussed. Some of the compounds synthesized showed anticancer properties when
      tested in vitro.

PMID- 22588575
TI  - Modeling the impact of partial hepatectomy on the hepatic hemodynamics using a
      rat model.
AB  - Due to the growing shortage of donor livers, more patients are waiting for
      transplantation. Living donor liver transplantation may help expanding the donor
      pool, but is often confronted with the small-for-size syndrome. Since the
      hemodynamic effects of partial hepatectomy are not fully understood, we developed
      an electrical rat liver model to compare normal with resected liver hemodynamics.
      Detailed geometrical data and 3-D reconstructions of the liver vasculature of two
      rats were gathered by combining vascular corrosion casting, micro-CT scanning,
      and image processing. Data extrapolations allowed obtaining a total liver
      pressure- and flow-driven electrical analog. Subsequently, virtual resections led
      to 70%, 80%, or 90% partial hepatectomy models. Results demonstrated
      hyperperfusion effects such as portal hypertension and elevated lobe-specific
      portal venous flows (11, 12, and 24 mmHg, and 1.0-3.0, 1.8-3.5, and 7.4 ml/min
      for 70%, 80%, and 90% hepatectomy, respectively). Comparison of two 90% resection
      techniques demonstrated different total arterial flows (0.28 ml/min versus 0.61
      ml/min), portal (24 mmHg versus 21 mmHg), and sinusoidal pressures (14 mmHg
      versus 9.5-12 mmHg), probably leading to better survival for lower portal and
      sinusoidal pressures. Toward the future, the models may be extrapolated to human
      livers and help us to optimize hepatectomy planning.

PMID- 22588577
TI  - Relationship satisfaction as a predictor of treatment response during cognitive
      behavioral sex therapy.
AB  - Although recent research suggests that individual cognitive behavioral therapy
      (CBT) may be an effective treatment for female sexual dysfunctions, we have
      little information regarding predictors of treatment response. The goal of the
      current study was to assess the degree to which pre-treatment relationship
      satisfaction predicted treatment response to cognitive behavioral sex therapy.
      Women with sexual dysfunction (n = 31, M age = 28 years, 77.4 % Caucasian)
      receiving cognitive-behavioral sex therapy with or without ginkgo biloba, as part
      of a wider randomized clinical trial, were assessed pre- and post-treatment using
      validated self-report measures of sexual satisfaction, sexual distress, sexual
      functioning, and relationship satisfaction. Pre-treatment relationship
      satisfaction predicted changes in sexual satisfaction and distress, but not
      sexual functioning. Women with higher relationship satisfaction at intake
      experienced larger gains in sexual satisfaction and distress over the course of
      treatment. Pre-treatment relationship satisfaction also moderated the association
      between changes in sexual functioning and changes in sexual distress, such that
      improved functioning was associated with decreased distress only for women
      entering therapy with high relationship satisfaction. These findings suggest
      that, for women with low relationship satisfaction before entering treatment,
      improvement in sexual functioning may not be enough to alleviate their sexual
      distress.

PMID- 22588578
TI  - A C84 selective porphyrin macrocycle with an adaptable cavity constructed through
      alkyne metathesis.
AB  - A bisporphyrin macrocycle was constructed from a porphyrin-based diyne monomer in
      one step through alkyne metathesis. The fullerene binding studies (C(60), C(70)
      and C(84)) showed the highest binding affinity of the macrocycle for C(84), which
      is in great contrast to its bisporphyrin four-armed cage analogue that showed the
      strongest binding with C(70).

PMID- 22588580
TI  - The interactive effects of exercise and gill remodeling in goldfish (Carassius
      auratus).
AB  - Gill remodeling in goldfish (Carassius auratus) is accomplished by the appearance
      or retraction of a mass of cells (termed the interlamellar cell mass or ILCM)
      between adjacent lamellae. Given the presumed effects of gill remodeling on
      diffusing capacity, the goals of the current study were (1) to determine the
      consequences of increased aerobic O(2) demand (swimming) on gill remodelling and
      (2) to assess the consequences of the presence or absence of the ILCM on aerobic
      swimming capacity. Fish acclimated to 7  degrees C exhibited a marked increase in
      the ILCM which occupied, on average, 70.0 +/- 4.1% of the total interlamellar
      channel area in comparison to an average ILCM area of only 28.3 +/- 0.9% in fish
      acclimated to 25  degrees C. Incrementally increasing swimming velocity in fish
      at 7  degrees C to achieve a maximum aerobic swimming speed (U (CRIT)) within
      approximately 3 h resulted in a marked loss of the ILCM area to 44.8 +/- 3.5%.
      Fish acclimated to 7  degrees C were subjected to 35 min swimming trials at 30,
      60 or 80% U (CRIT) revealing that significant loss of the ILCM occurred at
      swimming speeds exceeding 60% U (CRIT). Prior exposure of cold water-acclimated
      fish to hypoxia to induce shedding of the ILCM did not affect swimming
      performance when assessed under normoxic conditions (control fish U (CRIT) = 2.34
      +/- 0.30 body lengths s(-1); previously hypoxic fish U (CRIT) = 2.99 +/- 0.14
      body lengths s(-1)) or the capacity to raise rates of O(2) consumption with
      increasing swimming speeds. Because shedding of ILCM during U (CRIT) trials
      complicated the interpretation of experiments designed to evaluate the impact of
      the ILCM on swimming performance, additional experiments using a more rapid
      'ramp' protocol were performed to generate swimming scores. Neither prior hypoxia
      exposure nor a previous swim to U (CRIT) (both protocols are known to cause loss
      of the ILCM) affected swimming scores (the total distance swum during ramp U
      (CRIT) trials). However, partitioning all data based on the extent of ILCM
      coverage upon cessation of the swimming trial revealed that fish with less than
      40% ILCM coverage exhibited a significantly greater swimming score (539 +/- 86 m)
      than fish with greater than 50% ILCM coverage (285 +/- 70 m). Thus, while loss of
      the ILCM at swimming speeds exceeding 60% U (CRIT) confounds the interpretation
      of experiments designed to assess the impact of the ILCM on swimming performance,
      we suggest that the shedding of the ILCM, in itself, coupled with improved
      swimming scores in fish exhibiting low ILCM coverage (<40%), provide evidence
      that the ILCM in goldfish acclimated to cold water (7  degrees C) is indeed an
      impediment to aerobic swimming capacity.

PMID- 22588581
TI  - A survey of the prevalence of persistent pain after vaginal delivery: a pilot
      study.
AB  - INTRODUCTION: Pain that has lasted for 2 months is considered to be persistent,
      as defined by The International Association for the Study of Pain (IASP). To
      date, there is no data on the incidence of persistent pain after vaginal delivery
      available for Ireland. The aim of this pilot study is to determine the incidence
      of persistent pain in women post-vaginal delivery at 8 weeks postpartum in the
      Coombe Women's & Infants University Hospital, Dublin (CWIUH). METHODS: 50 women
      post-vaginal delivery at the CWIUH were recruited over a 2-month period. At 8
      weeks after delivery, the patients were contacted by telephone interview to
      assess the presence of pain, if any, using a modified painDETECT Questionnaire.
      RESULTS: The incidence of persistent pain at 8 weeks from our pilot study is 28%.

PMID- 22588582
TI  - Exploring the substructural space of indole-3-carboxamide derivatives binding to
      renin: a novel active-site spatial partitioning approach.
AB  - Renin has recently attracted much attention in the antihypertensive community,
      since this enzyme starts the angiotensin-converting cascade and forms the rate
      limiting step in this cascade. In the present study, we describe a new method
      called active-site spatial partitioning (ASSP) for quantitatively characterizing
      the nonbonding interaction profile between renin and the substructures of indole
      3-carboxamide derivatives-a novel class of achiral renin inhibitors that exhibit
      both high affinity and strong specificity for renin, thus blocking its active
      state-on the basis of structural models of protein-ligand complexes. It is shown
      that the ASSP-derived potential parameters are highly correlated with the
      experimentally measured activities of indole-3-carboxamides; the statistical
      models linking the parameters and activities using a sophisticated partial least
      squares regression technique show much promise as an effective and powerful tool
      for generalizing and predicting the pharmaceutical potencies and the
      physicochemical properties of other modified derivatives. Furthermore, by
      visually examining substructure-color plots generated by the ASSP procedure, it
      is found that the relative importance of nonbonding contributions to the
      recognition and binding of a ligand by renin is as follows: steric < hydrophobic
      < electrostatic. The polar and charged moieties that float on the surface of the
      ligand molecule play a critical role in conferring electrostatic stability and
      specificity to renin-ligand complexes, whereas the aromatic rings embedded in the
      core region of the ligand are the main source of hydrophobic and steric
      potentials that lead to substantial stabilization of the complex architecture.

PMID- 22588583
TI  - Lead compound design for TPR/COX dual inhibition.
AB  - The modes of action of TxA2 antagonists and COX-2 inhibitors were studied
      utilizing flexible ligand docking with postdocking minimization and ab initio
      interaction energy calculations. The resulting increased understanding of their
      binding interactions led to the design of a lead compound with chemical moieties
      that allowed efficient binding to both the thromboxane receptor and the COX-2
      enzyme. This compound is derived from allicin, a natural component of garlic, and
      is a good starting point for the development of anti-inflammatory drugs with
      fewer side effects or improved cardiovascular drugs.

PMID- 22588584
TI  - NMR and NQR study of Si-doped (6,0) zigzag single-walled aluminum nitride
      nanotube as n or P-semiconductors.
AB  - Density functional theory (DFT) calculations were performed to investigate the
      electronic structure properties of pristine and Si-doped aluminum nitride
      nanotubes as n or P-semiconductors at the B3LYP/6-31G* level of theory in order
      to evaluate the influence of Si-doped in the (6,0) zigzag AlNNTs. We extended the
      DFT calculation to predict the electronic structure properties of Si-doped
      aluminum nitride nanotubes, which are very important for production of solid
      state devices and other applications. To this aim, pristine and Si-doped AlNNT
      structures in two models (Si(N) and Si(Al)) were optimized, and then the
      electronic properties, the isotropic (CS(I)) and anisotropic (CS(A)) chemical
      shielding parameters for the sites of various (27)Al and (14)N atoms, NQR
      parameters for the sites of various of (27)Al and (14)N atoms, and quantum
      molecular descriptors were calculated in the optimized structures. The optimized
      structures, the electronic properties, NMR and NQR parameters, and quantum
      molecular descriptors for the Si(N) and Si(Al) models show that the Si(N) model
      is a more reactive material than the pristine or Si(Al) model.

PMID- 22588585
TI  - Interaction between alkaline earth cations and oxo ligands: a DFT study of the
      affinity of Mg2+ for carbonyl ligands.
AB  - The affinities of Mg(2+) for various substituted carbonyl ligands were determined
      at the DFT (B3LYP/6-31+G(d)) and semi-empirical (PM6) levels of theory. Two sets
      of carbonyl ligands were studied: monosubstituted [aldehydes R-CHO and RPh-CHO]
      and homodisubstituted [ketones R(2)C=O and (RPh)(2)C=O], where R = NH(2), OCH(3),
      OH, CH(3), H, F, Cl, Br, CN, or NO(2)). In the (RPh)(2)CO case, the R group was
      bonded to the para position of a phenyl ring. The enthalpies of interaction
      between the ligands and a pentaaquomagnesium(II) complex were calculated to
      determine the affinity of each ligand for the Mg(2+) cation and to correlate with
      geometrical and electronic parameters. These parameters exhibited the same trends
      for all of the ligands studied, showing that the affinity of Mg(2+) for electron
      donating ligands is higher than its affinity for electron-withdrawing ligands. In
      the complexes, electron-donating groups increase both the electrostatic and the
      covalent components of the Mg-ligand interaction. This behavior correlates with
      the Mg-O(carbonyl) distance and the ligand electron-donor strength.

PMID- 22588586
TI  - Rational design of a nitrite reductase based on myoglobin: a molecular modeling
      and dynamics simulation study.
AB  - Myoglobin (Mb) is an ideal scaffold protein for rational protein design mimicking
      native enzymes. We recently designed a nitrite reductase (NiR) based on sperm
      whale Mb by introducing an additional distal histidine (Leu29 to His29 mutation)
      and generating a distal tyrosine (Phe43 to Tyr43 mutation) in the heme pocket,
      namely L29H/F43Y Mb, to mimic the active site of cytochrome cd (1) NiR from Ps.
      aeruginosa that contains two distal histidines and one distal tyrosine. The
      molecular modeling and dynamics simulation study herein revealed that L29H/F43Y
      Mb has the necessary structural features of native cytochrome cd (1) NiR and can
      provide comparable interactions with nitrite as in native NiRs, which provides
      rationality for the protein design and guides the protein engineering.
      Additionally, the present study provides an insight into the relatively low NiR
      activity of Mb in biological systems.

PMID- 22588587
TI  - Regulation of medical devices used in diabetology in Europe: time for reform?

PMID- 22588591
TI  - Content-aware dark image enhancement through channel division.
AB  - The current contrast enhancement algorithms occasionally result in artifacts,
      overenhancement, and unnatural effects in the processed images. These drawbacks
      increase for images taken under poor illumination conditions. In this paper, we
      propose a content-aware algorithm that enhances dark images, sharpens edges,
      reveals details in textured regions, and preserves the smoothness of flat
      regions. The algorithm produces an ad hoc transformation for each image, adapting
      the mapping functions to each image's characteristics to produce the maximum
      enhancement. We analyze the contrast of the image in the boundary and textured
      regions, and group the information with common characteristics. These groups
      model the relations within the image, from which we extract the transformation
      functions. The results are then adaptively mixed, by considering the human vision
      system characteristics, to boost the details in the image. Results show that the
      algorithm can automatically process a wide range of images-e.g., mixed shadow and
      bright areas, outdoor and indoor lighting, and face images-without introducing
      artifacts, which is an improvement over many existing methods.

PMID- 22588588
TI  - Measuring therapeutic adherence in systemic lupus erythematosus with electronic
      monitoring.
AB  - OBJECTIVE: We used an electronic monitoring system to quantify adherence to
      prescribed oral therapies by patients with systemic lupus erythematosus (SLE).
      METHODS: Participants were included from a larger longitudinal study cohort of
      110 patients recruited from publicly-funded rheumatology clinics, 78 of whom
      agreed to have their SLE drug therapy electronically monitored for two years with
      the Medication Events Monitoring System (MEMS(r), AARDEX Group). Adherence was
      determined as the percentage of days (weeks for methotrexate) the patient took
      the medication as prescribed by the physician. Collected data included SLEDAI;
      SLICC damage index for SLE (SDI); medical outcome study social support survey
      (MOS-SSS); Center for Epidemiologic Studies depression scale (CESD); and quality
      of life (SF-12). RESULTS: Ninety percent of the cohort was female, 45% were
      Hispanic, and 49% were African-American. Mean age was 36.3 years, disease
      duration was 5.9 years, SLEDAI score was 3.2, and SDI score was 0.9. Adherence
      was 62% for all drugs combined and did not differ significantly for individual
      medications. Patients with more depression (p < 0.02), and higher number of pills
      taken daily (p < 0.02) were more likely to be non-adherent. Only one-fourth of
      the patients had an average adherence of >=80%; these patients had a better
      mental component score (SF-12) at 24 months than non-adherent patients (p <
      0.01). CONCLUSIONS: Electronic monitoring demonstrated that only one-fourth of
      the patients had an adherence rate >=80%. Polypharmacy and depression were
      associated with non-adherence.

PMID- 22588590
TI  - Development of GATE Monte Carlo simulation for a dual-head gamma camera.
AB  - GATE is a simulation code which is based on the Geant4 Monte Carlo code. This
      code was developed for simulation of nuclear medicine imaging systems. Our aim in
      this study was to use and validate GATE for simulating a Siemens E.Cam gamma
      camera. A dual-head gamma camera was used for modeling with GATE. Each head
      consisted of a collimator, aluminum layer, crystal, and head shielding. The back
      compartment consisted of photomultiplier tubes and electronic circuits behind the
      crystal. The photoelectric effect and Compton and Rayleigh scatter were included
      in the gamma transport process. The simulation validity was examined by
      comparison of measured parameters with calculated data including the energy
      spectrum, energy, spatial resolution, and sensitivity. To evaluate the imaging
      system, we compared the simulated and experimental images of a phantom. The
      simulated and measured energy spectra agreed well with regard to the position and
      height of the photopeak at 140 keV. The FWHMs at 140 keV were calculated to be
      equal to 14.10 and 13.37 keV, respectively. The energy resolutions were 10.07 and
      9.55%, and the sensitivities were 8.68 * 10(-5) and 8.69 * 10(-5) cps/MBq,
      respectively, for the simulated and measured results. The spatial resolution and
      imaging tests for a point, line, and node phantom showed good agreement between
      the simulated and measured results. Overall, the results showed good agreement
      between the measured and the simulated data. There was also excellent agreement
      between computational and actual images. This study demonstrated the flexibility
      and accuracy of GATE in SPECT simulation.

PMID- 22588592
TI  - Second-order optimization of mutual information for real-time image registration.
AB  - In this paper, we present a direct image registration approach that uses mutual
      information (MI) as a metric for alignment. The proposed approach is robust and
      gives an accurate estimation of a set of 2-D motion parameters in real time. MI
      is a measure of the quantity of information shared by signals. Although it has
      the ability to perform robust alignment with illumination changes, multimodality,
      and partial occlusions, few works have proposed MI-based applications related to
      spatiotemporal image registration or object tracking in image sequences because
      of some optimization problems, which we will explain. In this paper, we propose a
      new optimization method that is adapted to the MI cost function and gives a
      practical solution for real-time tracking. We show that by refining the
      computation of the Hessian matrix and using a specific optimization approach, the
      registration results are far more robust and accurate than the existing
      solutions, with the computation also being cheaper. A new approach is also
      proposed to speed up the computation of the derivatives and keep the same
      optimization efficiency. To validate the advantages of the proposed approach,
      several experiments are performed.

PMID- 22588593
TI  - Fluoride-triggered ESPT in the binding with sal(oph)en.
AB  - In this paper, anion binding and sensing affinity of the simple and easy-to-make
      salen, a typical class of ligand used comprehensively in metal coordination, was
      investigated. Results indicated that salophen was both a colorimetric and
      fluorescent selective chemosensor for fluoride ion, which operated by the anion
      induced conformational changes and subsequently excited-state intramolecular
      proton transfer (ESPT) process. The F(-)-induced quick response, as well as
      noticeable optical changes, suggested that anion-sensing mechanism maybe help to
      design and to synthesize the new preferential selective probes for F(-).

PMID- 22588594
TI  - Radical-mediated reduction of the dithiocarbamate group under tin-free
      conditions.
AB  - Reductive desulfurisation of dithiocarbamates is conveniently achieved using
      H(3)PO(2)-Et(3)N-ACCN in refluxing dioxane. Fused and spirocyclic beta-lactams,
      prepared through 4-exo trig carbamoyl radical cyclisation-dithiocarbamate group
      transfer reactions, are reduced without fragmentation of the strained 4-membered
      ring. Diethyl tetraacetyl-d-glucopyranosyl dithiocarbamate is selectively reduced
      with or without acyloxy group migration depending on reaction conditions and
      choice of reductant. Deuterium incorporation from D(3)PO(2)-Et(3)N is observed
      for a system involving a nucleophilic radical intermediate, but not in the case
      of the electrophilic radical obtained through acyloxy group migration on a
      glucose derivative.

PMID- 22588595
TI  - Differentiation of reactive and tumor metastatic lymph nodes with diffusion
      weighted and SPIO-enhanced MRI.
AB  - OBJECTIVES: Determination of lymphatic metastasis is of great importance for both
      treatment planning and patient prognosis. We aim to distinguish tumor metastatic
      lymph nodes (TLNs) and reactive lymph nodes (RLNs) with diffusion-weighted and
      superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI).
      MATERIALS AND METHODS: Ipsilateral popliteal lymph node metastasis or
      lymphadenitis model was established by hock injection of either luciferase
      expressing 4T1 murine breast cancer cells or complete Freund's adjuvant in male
      BALB/c mice. At different time points after inoculation, bioluminescence imaging
      and T(2)-weighted, diffusion-weighted, and SPIO-enhanced MRI were performed.
      Imaging findings were confirmed by histopathological staining. RESULTS: Size
      enlargement was observed in both TLNs and RLNs. At day 28, TLNs showed strong
      bioluminescence signal and bigger size than RLNs (p < 0.01). At early stages up
      to day 21, both TLNs and RLNs appeared homogeneous on diffusion-weighted imaging.
      At day 28, TLNs showed heterogeneous apparent diffusion coefficient (ADC) map
      with significantly higher average ADC value of 0.41 +/- 0.03 * 10(-3)mm(2)/s than
      that of RLNs (0.34 +/- 0.02 * 10(-3)mm(2)/s; p < 0.05). On SPIO-enhanced MRI,
      both TLNs and RLNs showed distinct T(2) signal reduction at day 21 after
      inoculation. At day 28, TLNs demonstrated partial uptake of the iron oxide
      particles, which was confirmed by Prussian blue staining. CONCLUSIONS: Both
      diffusion-weighted and SPIO-enhanced MRI can distinguish tumor metastatic lymph
      nodes from reactive lymph nodes. However, neither method is able to detect tumor
      metastasis to the draining lymph nodes at early stages.

PMID- 22588596
TI  - Dynamic contrast-enhanced MRI for monitoring bisphosphonate therapy in Paget's
      disease of bone.
AB  - PURPOSE: The purpose of this study was to evaluate changes in regional bone
      perfusion in Paget's disease (PD) following bisphosphonate therapy. We used
      dynamic contrast-enhanced MRI (DCE-MRI) for assessment of bone perfusion and
      compared MRI findings with alkaline phosphatase (AP) as a serum marker of bone
      turnover. MATERIALS AND METHODS: We examined 20 patients (8 women, 12 men, 66 +/-
      11 years) with symptomatic PD of the axial skeleton. Patients were selected for
      infusion therapy with the bisphosphonate pamidronate. The most affected bone of
      lumbar spine or pelvis was examined by DCE-MRI prior to therapy and after a 6
      month follow-up. The contrast uptake was evaluated using a two-compartment model
      with the parameters amplitude A and exchange rate constant K(ep). Color-coded
      parametric images were generated to visualize bone vascularization. RESULTS:
      After a 6-month follow-up there was a significant decrease in alkaline
      phosphatase and in DCE-MRI parameters A and K(ep) (p < 0.0001). Patients without
      previous bisphosphonate treatment showed a significantly greater decrease in
      alkaline phosphatase and K(ep) (p < 0.001). CONCLUSION: DCE-MRI shows a
      significant reduction in regional bone perfusion in PD following parenteral
      bisphosphonate treatment. Reduction in bone perfusion is greater in
      bisphosphonate-naive patients than in those who had been previously treated.

PMID- 22588597
TI  - Validity and reliability of preoperative templating in total hip arthroplasty
      using a digital templating system.
AB  - OBJECTIVES: To evaluate the validity, interobserver reliability, and
      intraobserver reproducibility of a digital templating system, the MdeskTM in
      preoperative templating in cemented and reverse hybrid total hip arthroplasty
      (THA). MATERIALS AND METHODS: Validity was evaluated by comparing the planned cup
      size, stem size, CCD angles, and neck length with the components used in 129
      patients operated with cemented and reverse hybrid THA. The reliability was
      measured by comparing the templating results of two surgeons with each other
      (interobserver) and the results of two templatings carried out by first surgeon
      (intraobserver). The leg length discrepancy was measured before and after the
      operation to assess the templating ability to correct it. RESULTS: The MdeskTM
      system showed good validity (kappa value ranged from 0.64 to 0.96), especially
      when one size over and under the planned size were included. No difference
      between cemented and cementless stems was found. The interobserver reliability
      ranged from fair (kappa 0.23) to substantial (kappa 0.61) while the intraobserver
      reproducibility ranged from substantial (kappa 0.70) to excellent (kappa 0.82).
      Templating and intraoperative measures succeeded to restore the leg length.
      CONCLUSIONS: The MdeskTM system has comparable validity and reliability with
      other templating systems used in clinical practice. We recommend that the same
      surgeon who does the preoperative radiographic templating to also perform the
      operation. Further studies are required to evaluate the results of succeeded
      templating in the long run.

PMID- 22588598
TI  - Optimal assessment of paediatric IBD with MRI and barium follow-through.
AB  - OBJECTIVES: The present UK criterion standard for assessing children with
      suspected inflammatory bowel disease (IBD) is upper endoscopy, ileocolonoscopy,
      and barium follow-through (BaFT). Significant doses of radiation, unpalatable
      contrast, and volume intolerance are involved with BaFT. Practice in
      investigating Crohn disease (CD) is changing with the increasing use of magnetic
      resonance imaging (MRI). The aim of the present study was to compare BaFT and a
      new abdominal MRI protocol in a paediatric IBD population. METHODS: All
      consecutive patients with a new diagnosis of IBD or requiring reassessment from
      September 2008 to December 2010 were investigated with both abdominal MRI and
      BaFT in accordance with a specific local paediatric IBD protocol. The studies
      were reported by nonblinded radiologists with an interest in gastrointestinal
      imaging. The reports were compared in conjunction with case note review. RESULTS:
      Eighty-seven patients underwent both BaFT and MRI abdomen. Thirty-one percent of
      patients had additional pathology on MRI, not seen on the BaFT. Sixty-seven
      percent of patients (n=59) had an MRI finding equivalent to BaFT. Using histology
      as a criterion standard for detecting terminal ileal disease, BaFT had a
      sensitivity and specificity of 76% and 67%, and MRI had a sensitivity and
      specificity of 83% and 95%, respectively. CONCLUSIONS: This is the largest series
      of small bowel MRI in a paediatric population. MRI reports were at least
      equivalent to BaFT. MRI had higher sensitivity and, particularly, specificity in
      detecting terminal ileal pathology. These findings suggest that MRI should become
      the criterion standard investigation in children with IBD in centres with
      appropriate expertise, with zero radiation exposure being highly advantageous.

PMID- 22588600
TI  - Magnet ingestion in children and teenagers:  an emerging health concern for
      pediatricians and pediatric subspecialists.

PMID- 22588599
TI  - Concomitant gastroparesis negatively affects children with functional gallbladder
      disease.
AB  - OBJECTIVES: The aim of the present study was to determine whether concomitant
      gastroparesis and biliary dyskinesia (BD) occur in children, and if so, to
      determine whether concomitant gastroparesis affects clinical outcome in children
      with BD. METHODS: We conducted a retrospective chart review of children with BD
      (ejection fraction <35% on cholescintigraphy, with no other metabolic or
      structural cause) who completed a solid-phase gastric emptying scintigraphy scan
      within 12 months of abnormal cholescintigraphy. Children were classified into 1
      of 4 clinical outcome groups (excellent, good, fair, poor). RESULTS: Thirty-five
      children with a mean follow-up time of 23.1+/-17.3 (standard deviation) months
      were included. Twenty (57%) children were identified as having concomitant
      gastroparesis (GP) with BD. Children with concomitant GP were more likely to have
      a poor clinical outcome compared with those with BD alone (P<0.005). In children
      undergoing cholecystectomy, those with concomitant GP were more likely to have a
      fair or poor clinical outcome compared with those with BD alone (P<0.01). Factors
      predicting a more favorable clinical outcome were having BD alone and not having
      limitations in activity (eg, school absences) at the time of presentation.
      CONCLUSIONS: Concomitant GP may occur in children with functional gallbladder
      disorders. Concomitant GP may negatively affect clinical outcome in children with
      BD.

PMID- 22588601
TI  - A simplified technique for producing an ischemic wound model.
AB  - One major obstacle in current diabetic wound research is a lack of an ischemic
      wound model that can be safely used in diabetic animals. Drugs that work well in
      non-ischemic wounds may not work in human diabetic wounds because vasculopathy is
      one major factor that hinders healing of these wounds. We published an article in
      2007 describing a rabbit ear ischemic wound model created by a minimally invasive
      surgical technique. Since then, we have further simplified the procedure for
      easier operation. On one ear, three small skin incisions were made on the
      vascular pedicles, 1-2 cm from the ear base. The central artery was ligated and
      cut along with the nerve. The whole cranial bundle was cut and ligated, leaving
      only the caudal branch intact. A circumferential subcutaneous tunnel was made
      through the incisions, to cut subcutaneous tissues, muscles, nerves, and small
      vessels. The other ear was used as a non-ischemic control. Four wounds were made
      on the ventral side of each ear. This technique produces 4 ischemic wounds and 4
      non-ischemic wounds in one animal for paired comparisons. After surgery, the
      ischemic ear was cool and cyanotic, and showed reduced movement and a lack of
      pulse in the ear artery. Skin temperature of the ischemic ear was 1-10  degrees C
      lower than that on the normal ear and this difference was maintained for more
      than one month. Ear tissue high-energy phosphate contents were lower in the
      ischemic ear than the control ear. Wound healing times were longer in the
      ischemic ear than in the non-ischemic ear when the same treatment was used. The
      technique has now been used on more than 80 rabbits in which 23 were diabetic
      (diabetes time ranging from 2 weeks to 2 years). No single rabbit has developed
      any surgical complications such as bleeding, infection, or rupture in the skin
      incisions. The model has many advantages, such as little skin disruption, longer
      ischemic time, and higher success rate, when compared to many other models. It
      can be safely used in animals with reduced resistance, and can also be modified
      to meet different testing requirements.

PMID- 22588602
TI  - Development of Ohmic nanocontacts via surface modification for nanowire-based
      electronic and optoelectronic devices: ZnO nanowires as an example.
AB  - We demonstrated a nanocontacting scheme using a focus ion beam (FIB) system
      without further heat treatment for ZnO nanowires. This scheme includes Ga ion
      surface modification and direct-write Pt deposition induced by Ga ion, leading to
      an Ohmic nanocontact with a specific contact resistance as low as 2.5 * 10(
      6)Omega cm(2). Temperature-dependent measurements show that the transport of the
      FIB-Pt contact on the ZnO nanowire with local surface modification is governed by
      field emission tunneling. Taking advantage of area-selected and room-temperature
      processes, Ga ion surface modification and direct-write Pt deposition using a FIB
      system demonstrates a feasible Ohmic scheme.

PMID- 22588603
TI  - Quantification of antiangiogenic and antivascular drug activity by kinetic
      analysis of DCE-MRI data.
AB  - Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can be used to
      quantify the response of tumors to vascular targeting agents. Tumor response is
      frequently assessed using mathematical models that describe the distribution of
      contrast agents over time as a function of fundamental characteristics of
      vascular physiology. Generally, mathematical models of biological systems are
      abstractions that attempt to retain fundamental physiologic characteristics,
      thereby allowing for multiple potential modeling approaches and structures.
      Various DCE-MRI modeling techniques are discussed in this article.

PMID- 22588604
TI  - Compartment-specific gene regulation of the CAR inducer efavirenz in vivo.
AB  - Nuclear receptors such as the constitutive androstane receptor (CAR) are central
      factors that link drug exposure to the activities of drug metabolism and
      elimination. In order to determine the in vivo effects of efavirenz, a CAR
      activator, the expression of target genes was determined in duodenal biopsies
      obtained from 12 healthy volunteers before treatment and after 10 days of
      treatment with efavirenz; concomitant administration of the cholesterol inhibitor
      ezetimibe produced no significant difference. However, in in vitro studies,
      efavirenz significantly increased CYP2B6 expression in several cell types,
      suggesting that the drug transactivates CAR. This hypothesis is supported by our
      findings that there is significant induction of CAR target genes in in vivo
      peripheral blood mononuclear cells (PBMCs) isolated from healthy volunteers
      treated with multiple doses of efavirenz. The impact of efavirenz on hepatic
      metabolism in vivo was confirmed by significant changes in plasma 4beta
      hydroxycholesterol and bilirubin levels and the area under the curve (AUC) of
      efavirenz. Induction of CYP2B6 mRNA expression correlated with the decrease in
      the AUC of efavirenz (r = 0.61; P = 0.036). Taken together, our results provide
      evidence that efavirenz exerts compartment-specific inductive capacity in vivo.

PMID- 22588605
TI  - Antidepressant use and risk of out-of-hospital cardiac arrest: a nationwide case
      time-control study.
AB  - Treatment with some types of antidepressants has been associated with sudden
      cardiac death. It is unknown whether the increased risk is due to a class effect
      or related to specific antidepressants within drug classes. All patients in
      Denmark with an out-of-hospital cardiac arrest (OHCA) were identified (2001
      2007). Association between treatment with specific antidepressants and OHCA was
      examined by conditional logistic regression in case-time-control models. We
      identified 19,110 patients with an OHCA; 2,913 (15.2%) were receiving
      antidepressant treatment at the time of OHCA, with citalopram being the most
      frequently used type of antidepressant (50.8%). Tricyclic antidepressants (TCAs;
      odds ratio (OR) = 1.69, confidence interval (CI): 1.14-2.50) and selective
      serotonin reuptake inhibitors (SSRIs; OR = 1.21, CI: 1.00-1.47) were both
      associated with comparable increases in risk of OHCA, whereas no association was
      found for serotonin-norepinephrine reuptake inhibitors/noradrenergic and specific
      serotonergic antidepressants (SNRIs/NaSSAs; OR = 1.06, CI: 0.81-1.39). The
      increased risks were primarily driven by: citalopram (OR = 1.29, CI: 1.02-1.63)
      and nortriptyline (OR = 5.14, CI: 2.17-12.2). An association between cardiac
      arrest and antidepressant use could be documented in both the SSRI and TCA
      classes of drugs.

PMID- 22588606
TI  - Active safety monitoring of newly marketed medications in a distributed data
      network: application of a semi-automated monitoring system.
AB  - We developed a semi-automated active monitoring system that uses sequential
      matched-cohort analyses to assess drug safety across a distributed network of
      longitudinal electronic health-care data. In a retrospective analysis, we show
      that the system would have identified cerivastatin-induced rhabdomyolysis. In
      this study, we evaluated whether the system would generate alerts for three drug
      outcome pairs: rosuvastatin and rhabdomyolysis (known null association),
      rosuvastatin and diabetes mellitus, and telithromycin and hepatotoxicity (two
      examples for which alerting would be questionable). Over >5 years of monitoring,
      rate differences (RDs) in comparisons of rosuvastatin with atorvastatin were -0.1
      cases of rhabdomyolysis per 1,000 person-years (95% confidence interval (CI): 
      0.4, 0.1) and -2.2 diabetes cases per 1,000 person-years (95% CI: -6.0, 1.6). The
      RD for hepatotoxicity comparing telithromycin with azithromycin was 0.3 cases per
      1,000 person-years (95% CI: -0.5, 1.0). In a setting in which false positivity is
      a major concern, the system did not generate alerts for the three drug-outcome
      pairs.

PMID- 22588607
TI  - Carboxylesterase 1 polymorphism impairs oseltamivir bioactivation in humans.
AB  - Bioactivation of the antiviral agent oseltamivir to active oseltamivir
      carboxylate is catalyzed by carboxylesterase 1 (CES1). After the screening of 860
      healthy Finnish volunteers for the CES1 c.428G>A (p.Gly143Glu, rs121912777)
      polymorphism, a pharmacokinetic study with 75 mg oseltamivir was carried out in
      c.428G>A carriers and noncarriers. Heterozygous c.428GA carriers (n = 9) had 18%
      larger values of oseltamivir area under the plasma concentration-time curve from
      0 h to infinity (AUC(0-infinity)) (P = 0.025) and 23% smaller carboxylate-to
      oseltamivir AUC(0-infinity) ratio (P = 0.006) than noncarriers (n = 12). This
      shows that the CES1 c.428G>A polymorphism impairs oseltamivir bioactivation in
      humans.

PMID- 22588609
TI  - Water-dispersed quantum dots of coordination polymers with strong
      photoluminescence.
AB  - Coordination polymers PZn quantum dots with a uniform diameter of 3 +/- 0.5 nm
      were successfully prepared. The PZn QDs exhibit excellent water dispersibility,
      high photoluminescence, outstanding photostability and remarkable
      biocompatibility. The results of cellular experiments show that the PZn QDs are
      highly suitable for long-term cell imaging.

PMID- 22588610
TI  - Approximate optimal control design for nonlinear one-dimensional parabolic PDE
      systems using empirical eigenfunctions and neural network.
AB  - This paper addresses the approximate optimal control problem for a class of
      parabolic partial differential equation (PDE) systems with nonlinear spatial
      differential operators. An approximate optimal control design method is proposed
      on the basis of the empirical eigenfunctions (EEFs) and neural network (NN).
      First, based on the data collected from the PDE system, the Karhunen-Loeve
      decomposition is used to compute the EEFs. With those EEFs, the PDE system is
      formulated as a high-order ordinary differential equation (ODE) system. To
      further reduce its dimension, the singular perturbation (SP) technique is
      employed to derive a reduced-order model (ROM), which can accurately describe the
      dominant dynamics of the PDE system. Second, the Hamilton-Jacobi-Bellman (HJB)
      method is applied to synthesize an optimal controller based on the ROM, where the
      closed-loop asymptotic stability of the high-order ODE system can be guaranteed
      by the SP theory. By dividing the optimal control law into two parts, the linear
      part is obtained by solving an algebraic Riccati equation, and a new type of HJB
      like equation is derived for designing the nonlinear part. Third, a control
      update strategy based on successive approximation is proposed to solve the HJB
      like equation, and its convergence is proved. Furthermore, an NN approach is used
      to approximate the cost function. Finally, we apply the developed approximate
      optimal control method to a diffusion-reaction process with a nonlinear spatial
      operator, and the simulation results illustrate its effectiveness.

PMID- 22588608
TI  - Operational implementation of prospective genotyping for personalized medicine:
      the design of the Vanderbilt PREDICT project.
AB  - The promise of "personalized medicine" guided by an understanding of each
      individual's genome has been fostered by increasingly powerful and economical
      methods to acquire clinically relevant information. We describe the operational
      implementation of prospective genotyping linked to an advanced clinical decision
      support system to guide individualized health care in a large academic health
      center. This approach to personalized medicine entails engagement between patient
      and health-care provider, identification of relevant genetic variations for
      implementation, assay reliability, point-of-care decision support, and necessary
      institutional investments. In one year, approximately 3,000 patients, most of
      whom were scheduled for cardiac catheterization, were genotyped on a multiplexed
      platform that included genotyping for CYP2C19 variants that modulate response to
      the widely used antiplatelet drug clopidogrel. These data are deposited into the
      electronic medical record (EMR), and point-of-care decision support is deployed
      when clopidogrel is prescribed for those with variant genotypes. The
      establishment of programs such as this is a first step toward implementing and
      evaluating strategies for personalized medicine.

PMID- 22588611
TI  - Multilayer Architectures for Facial Action Unit Recognition.
AB  - In expression recognition and many other computer vision applications, the
      recognition performance is greatly improved by adding a layer of nonlinear
      texture filters between the raw input pixels and the classifier. The function of
      this layer is typically known as feature extraction. Popular filter types for
      this layer are Gabor energy filters (GEFs) and local binary patterns (LBPs).
      Recent work [1] suggests that adding a second layer of nonlinear filters on top
      of the first layer may be beneficial. However, it is unclear what is the best
      architecture of layers and selection of filters. In this paper, we present a
      thorough empirical analysis of the performance of single-layer and dual-layer
      texture-based approaches for action unit recognition. For the single hidden layer
      case, GEFs perform consistently better than LBPs, which may be due to their
      robustness to jitter and illumination noise as well as to their ability to encode
      texture at multiple resolutions. For dual-layer case, we confirm that, while
      small, the benefit of adding this second layer is reliable and consistent across
      data sets. Interestingly for this second layer, LBPs appear to perform better
      than GEFs. 

PMID- 22588612
TI  - Reactivation of effluent granular sludge from a high-rate Anammox reactor after
      storage.
AB  - In this study, effluent sludge from a high-rate Anammox reactor was used to re
      start new Anammox reactors for the reactivation of Anammox granular sludge.
      Different start-up strategies were evaluated in six upflow anaerobic sludge
      blanket (UASB) reactors (R(1)-R(6)) for their effect on nitrogen removal
      performance. Maximal nitrogen removal rates (NRRs) greater than 20 kg N/m(3)/day
      were obtained in reactors R(3)-R(5), which were seeded with mixed Anammox sludge
      previously stored for approximately 6 months and 1 month. A modified Boltzmann
      model describing the evolution of the NRR fit the experimental data well. An
      amount of sludge added to the UASB reactor or decreasing the loading rate proved
      effective in relieving the substrate inhibition and increasing the NRR. The
      modified Stover-Kincannon model fit the nitrogen removal data in the Anammox
      reactors well, and the simulation results showed that the Anammox process has
      great nitrogen removal potential. The observed inhibition in the Anammox reactors
      may have been caused by high levels of free ammonia. The sludge used to seed the
      reactors did not settle well; sludge flotation was observed even after the
      reactors were operated for a long time at a floating upward velocity (F(s)) of
      greater than 100 m/h. The settling sludge, however, exhibited good settling
      properties. Scanning electron microscopy showed that the Anammox granules
      consisted mainly of spherical and elliptical bacteria with abundant filaments on
      their surface. Hollows in the granules were also present, which may have
      contributed to sludge floatation.

PMID- 22588615
TI  - Degradation dynamics of the insecticide: clothianidin (Dantop 50 % WDG) in a tea
      field ecosystem.
AB  - The fate of clothianidin [(E)-1-(2-chloro-1, 3-thiazol-5-ylmethyl)-3-methyl-2
      nitroguanidine] applied to tea plant was studied at two location in West Bengal,
      India. The insecticide was applied in Tea field at two doses @30 and 60 g.a.i./ha
      during June-July 2009. Solid-phase extraction and liquid-liquid extraction was
      employed for the determination of this insecticide in tea samples. Clothianidin
      residues were analyzed and estimated quantitatively by HPLC at lambda(max) 250
      nm. The observed half life values of made tea and green tea leaf ranges from 3.71
      to 4.07 days and 4.07 to 4.49 days respectively.

PMID- 22588614
TI  - Cytomegalovirus infection and the gastrointestinal tract.
AB  - Cytomegalovirus (CMV) infection is common worldwide, but the majority are
      asymptomatic. However, during initial infection or reactivation, CMV can cause
      tissue-invasive end-organ damage including in the gastrointestinal tract,
      especially in immunocompromised individuals. Gastrointestinal CMV disease can
      present with myriad of symptoms and be highly variable endoscopically. In this
      article we review the manifestations of CMV infection within the luminal
      gastrointestinal tract and discuss the options for diagnosis and management.

PMID- 22588616
TI  - Fast localization and segmentation of optic disk in retinal images using
      directional matched filtering and level sets.
AB  - The optic disk (OD) center and margin are typically requisite landmarks in
      establishing a frame of reference for classifying retinal and optic nerve
      pathology. Reliable and efficient OD localization and segmentation are important
      tasks in automatic eye disease screening. This paper presents a new, fast, and
      fully automatic OD localization and segmentation algorithm developed for retinal
      disease screening. First, OD location candidates are identified using template
      matching. The template is designed to adapt to different image resolutions. Then,
      vessel characteristics (patterns) on the OD are used to determine OD location.
      Initialized by the detected OD center and estimated OD radius, a fast, hybrid
      level-set model, which combines region and local gradient information, is applied
      to the segmentation of the disk boundary. Morphological filtering is used to
      remove blood vessels and bright regions other than the OD that affect
      segmentation in the peripapillary region. Optimization of the model parameters
      and their effect on the model performance are considered. Evaluation was based on
      1200 images from the publicly available MESSIDOR database. The OD location
      methodology succeeded in 1189 out of 1200 images (99% success). The average mean
      absolute distance between the segmented boundary and the reference standard is
      10% of the estimated OD radius for all image sizes. Its efficiency, robustness,
      and accuracy make the OD localization and segmentation scheme described herein
      suitable for automatic retinal disease screening in a variety of clinical
      settings.

PMID- 22588617
TI  - Near-affine-invariant texture learning for lung tissue analysis using isotropic
      wavelet frames.
AB  - We propose near-affine-invariant texture descriptors derived from isotropic
      wavelet frames for the characterization of lung tissue patterns in high
      resolution computed tomography (HRCT) imaging. Affine invariance is desirable to
      enable learning of nondeterministic textures without a priori localizations,
      orientations, or sizes. When combined with complementary gray-level histograms,
      the proposed method allows a global classification accuracy of 76.9% with
      balanced precision among five classes of lung tissue using a leave-one-patient
      out cross validation, in accordance with clinical practice.

PMID- 22588618
TI  - Invited commentary on modified classification of surgical meshes for hernia
      repair. [corrected].

PMID- 22588619
TI  - Changes in intracranial CSF distribution after ETV.
AB  - OBJECTIVE: The aim of this prospective study was to analyze the changes in
      cerebrospinal fluid (CSF) distribution after endoscopic third
      ventriculocisternostomy (ETV). METHODS: Twenty-two hydrocephalic children (eight
      boys, aged 3 months to 17 years) candidates for ETV were studied by preoperative
      brain magnetic resonance (MR) and repeated post-ETV MRs at established time
      intervals. A volumetric analysis of CSF distribution after ETV was performed
      using a specific software. RESULTS: Fifteen children had an uneventful follow-up,
      whereas four required a second ETV due to a secondary closure of the stoma, one
      died of acute intracranial hypertension, and two needed an extrathecal shunt. A
      progressive reduction in the volume of the ventricles was found in case of
      successful ETV during the follow-up period. The ventricular volumes were reduced
      in average of 76 % of the initial volume at day 3, 69 % at 2 weeks, 42 % at 2
      months, and 40 % at 6 months. This finding was associated with an enlargement of
      subarachnoid spaces which increased in case of successful ETV (192 % of initial
      volume at day 3; 210 % at day 15; 428 % at 2 months; and 468 % at 6 months). In
      case of secondary closure of the stoma, the distribution of intra- and
      extraventricular CSF tended to go back to the preoperative status. CONCLUSION:
      Volume variations of the ventricles and the subarachnoid spaces are a good
      indicator of the efficacy of the ETV.

PMID- 22588620
TI  - Bone grafts as vancomycin carriers in local therapy of resistant infections.
AB  - The level of an antibiotic capable of inhibiting the etiological agent at the
      site of infection is an essential prerequisite for successful antibiotic therapy.
      In some cases, locally applied antibiotics may compensate for limitations of
      systemic administration and shorten systemic therapy. We aimed at verifying to
      what extent vancomycin (Van) bound to ground bone grafts is usable in the
      treatment of serious infections. The levels of released Van significantly
      exceeded the Van minimum inhibitory concentration, which can suppress Van
      sensitive staphylococci and Van intermediate Staphylococcus aureus, for the whole
      period of a 16-day measurement. Our results indicate that bone grafts can be used
      as Van carriers in therapy of osteomyelitis caused by Van-sensitive
      Staphylococcus strains.

PMID- 22588621
TI  - Effects of volatile fatty acids, ammonium and agitation on thermophilic methane
      production from biogas plant sludge in lab-scale experiments.
AB  - The effects of different volatile fatty acids (VFA, formate, acetate, propionate
      and butyrate), ammonium (NH (4) (+)) and agitation on methane (CH(4)) production
      were determined in 120-mL serum bottles. We showed that the addition of formate
      did not lead to an inhibition of methanogenesis until a concentration of 120
      mmol/L. A complete inhibition of methanogenesis was detected in variants
      containing 360 mmol/L formate or propionate until day 3 but the production
      started afterwards within next 2 days. This might indicate a kind of adaptation
      to the higher volatile fatty acid concentrations. Increasing NH (4) (+)
      concentrations led to higher initial CH(4) production, with an optimum at 120
      mmol/L. The addition of 720 mmol/L NH (4) (+) led to a complete inhibition until
      day 3; subsequently, CH(4) production started again on day 5 though it was still
      significantly lower compared to the other variants. Finally, also the speed of
      agitation showed significant effects on methanogenesis. The CH(4) production from
      complex carbon sources was most favourable at a moderate agitation of 150 rpm of
      the lab-scale serum bottles. A lower or higher speed brought about a distinct
      reduction of CH(4) production.

PMID- 22588622
TI  - Nursing student perceptions of disability and preparation to care for people with
      intellectual disabilities.
AB  - As people with intellectual disabilities live longer and develop more chronic
      illnesses, nurses will have increasing contact with them. Therefore, nurses must
      have both an accurate understanding of and a positive attitude toward this
      population to ensure optimal nursing care is received. A cross-sectional survey
      of second-year and fourth-year nursing students measured their perceptions of
      disability, their contact with people with intellectual disabilities, and their
      perceptions of education to prepare them to care for people with intellectual
      disabilities. Students most often identified disability as physical, using a
      wheelchair to represent that perception. Students were confident in their ability
      to transfer many of the skills they learned to care for people with intellectual
      disabilities but identified a need for more education about providing that care.
      Curricular changes to enhance nursing students' awareness and understanding of
      people with intellectual disabilities are recommended.

PMID- 22588623
TI  - Quasi-experimental evaluation of a substance use awareness educational
      intervention for nursing students.
AB  - This article reports on a study that evaluated the effectiveness of an
      educational intervention, Addressing Nurse Impairment, for addressing nursing
      students' knowledge acquisition, changes in self-efficacy to intervene, and
      changes in substance abuse stigma. A gap exists in nursing students' education
      regarding the risks of addiction within the profession and how to handle a
      colleague suspected of having a substance use disorder. The seminar was adapted
      from an existing evidence-based prevention program called Team Awareness, as well
      as information from focus groups and a pilot test. A quasi-experimental pretest
      posttest design was used to evaluate the effect of the seminar. When the control
      and experimental groups were compared, the results indicated that the seminar
      significantly affected knowledge and self-efficacy to intervene but did not
      significantly affect stigma. This research contributes to the body of evidence
      related to educational interventions for nursing students regarding substance
      abuse in the nursing profession.

PMID- 22588624
TI  - Serum vitamin D insufficiency and diabetes status in three ethnic minority
      groups.
AB  - The purpose of this study was to investigate the association between 25
      hydroxyvitamin D [25(OH)D] levels and diabetes status in three ethnicities. This
      cross sectional study included Cuban Americans (n = 199), Haitian Americans (n =
      253) and African Americans (n = 248) with and without type 2 diabetes (T2D) from
      Florida, U.S. Recruitment of participants was through mailing lists (Cuban
      Americans and African Americans) and community based sources (Haitian Americans).
      Adjusted logistic regression analysis indicated significant differences in the
      odds of having insufficient 25(OH)D levels by ethnicity [P < 0.001], diabetes
      status [P < 0.001], and their interaction [P < 0.001]. Holm's modified Bonferroni
      method showed that only Cuban Americans without T2D had significantly lower odds
      of having insufficient 25(OH)D compared to all other groups. Haitian American and
      African American participants and participants having T2D had the greatest risk
      of 25(OH)D insufficiency. Future studies should focus on the role of vitamin D
      supplementation and diabetes outcomes across ethnic groups.

PMID- 22588625
TI  - Role of scintigraphy with 99mTc-infliximab in predicting the response of
      intraarticular infliximab treatment in patients with refractory monoarthritis.
AB  - PURPOSE: The rationale for the present study was to evaluate the predictive role
      of (99m)Tc-infliximab scintigraphy in therapy decision-making in patients with
      refractory monoarthritis and also candidates for intraarticular (IA) infliximab
      treatment. METHODS: We studied 12 patients (5 with rheumatoid arthritis and 7
      with spondyloarthropathy) with active monoarthritis (11 knees and 1 ankle) that
      had lasted for at least 3 months. Patients were evaluated clinically and
      ultrasonographically at baseline and 12 weeks after IA administration of
      infliximab. At the same time-points, (99m)Tc-infliximab scintigraphy was
      performed: planar anterior and posterior images of arthritic joints were acquired
      at 6 and 20 h after injection and target-to-background (T/B) ratios were
      calculated. RESULTS: After treatment, a significant improvement in clinical and
      ultrasonographic parameters was recorded in six patients. Three patients had a
      partial response and three did not respond. Regarding scintigraphic evaluation,
      the T/B ratio analysis showed a significantly higher uptake in affected than in
      nonaffected joints before therapy (1.78 +/- 0.46 vs. 1.29 +/- 0.27, p = 0.006 at
      6 h; 2.05 +/- 0.50 vs. 1.41 +/- 0.36 at 20 h, p = 0.002), and mean uptake at 20 h
      was also significantly higher than at 6 h (p = 0.0004). Scintigraphy showed a
      significant decrease in posttherapy T/B ratios of the affected joints (p = 0.0001
      at 6 h and p = 0.0001 at 20 h), indicating a reduction in TNF into the affected
      joints. Most importantly, responders showed a significantly higher percentage
      increase in pretherapy uptake from 6 h to 20 h in the affected joints than
      nonresponders (p = 0.00001). CONCLUSION: The results of the present investigation
      suggest that (99m)Tc-infliximab scintigraphy could be a useful tool to predict
      the clinical response to IA infliximab treatment in patients with refractory
      monoarthritis.

PMID- 22588626
TI  - Cardiac beta-adrenergic receptor density and myocardial systolic function in the
      remote noninfarcted region after prior myocardial infarction with left
      ventricular remodelling.
AB  - PURPOSE: After myocardial infarction (MI), left ventricular (LV) remodelling is
      observed in noninfarcted LV myocardium. LV remodelling is closely associated with
      systolic heart failure. Since myocardial dysfunction is related to the
      downregulation of cardiac postsynaptic beta-adrenergic receptors (beta-AR), we
      hypothesized that a reduction in beta-AR density may be manifested in the remote
      noninfarcted region and such reduction may be related to myocardial systolic
      dysfunction. Accordingly, we assessed beta-AR density with a focus on the remote
      noninfarcted region. METHODS: Cardiac PET was performed in 15 patients with a
      prior MI and 10 age-matched healthy controls using (11)C-CGP 12177, a radioligand
      for beta-receptors. The maximum number of available specific (11)C-CGP 12177
      binding sites per gram of tissue was calculated in regions of interest using an
      established graphical method. LV regional systolic function was assessed based on
      peak systolic myocardial strain on the LV wall in the longitudinal direction
      using two-dimensional ultrasound speckle tracking imaging. LV volumes and LV
      ejection fraction (EF) were also measured. RESULTS: The LV end-diastolic volume
      index was significantly larger in patients than in controls (67.8 +/- 16.9 vs.
      49.1 +/- 12.3 ml/m(2), p < 0.01). Significant differences in beta-AR density were
      observed among three areas: the apical area in controls (where the lowest beta-AR
      density was observed), the remote noninfarcted region of patients and LVEF >= 55
      %, and the remote noninfarcted region of patients and LVEF <55 % (5.8 +/- 2.1 vs.
      4.2 +/- 0.7 vs. 3.3 +/- 0.7 pmol/ml, p < 0.01, ANOVA). Peak systolic myocardial
      strain was significantly reduced in the remote noninfarcted LV wall in patients
      with a prior anterior wall MI compared with that in the corresponding wall in
      controls (-15.5 +/- 2.5 vs. -20.1 +/- 2.2 %, p < 0.001). A similar finding was
      also observed in patients with a prior inferior wall MI. CONCLUSION: In the
      remote noninfarcted region in patients, beta-AR downregulation was observed,
      which was related to deterioration of local myocardial systolic function.

PMID- 22588627
TI  - Hepatic artery injection of 131I-labelled metuximab combined with
      chemoembolization for intermediate hepatocellular carcinoma: a prospective
      nonrandomized study.
AB  - PURPOSE: Hepatocellular carcinoma (HCC) is the fifth and seventh most common
      cause of cancer in men and women, respectively. Transcatheter arterial
      chemoembolization (TACE) is the standardized therapy for the intermediate stage
      of HCC. However, the 3-year overall survival remains low (<30 %) in these
      patients. Thus, there is a critical need for the development of treatment
      modalities to improve the survival rate. This study aimed to evaluate whether the
      combination of (131)I-metuximab with chemoembolization could improve treatment
      efficiency. METHODS: Between January 2009 and January 2010, a prospective two-arm
      nonrandomized study was performed in patients with intermediate HCC. Of 138
      patients, 68 (combination therapy group) received 132 courses of intraarterial
      (131)I-metuximab injections combined with chemoembolization (mean 1.94 per
      patient, median 2, range 1-2), followed by 152 sessions of TACE (mean 2.24 per
      patient, median 2, range 0-4). The remaining 70 patients (monotherapy group)
      received 296 sessions of TACE (mean 4.23 per patient, median 4, range 1-7).
      RESULTS: The overall median survival times for the combination therapy group and
      the group treated only with TACE were 26.7 months (95 % CI 20.7-31.3 months) and
      20.6 months (95 % CI 15.3-24.7 months), respectively. The combination therapy
      group had a significantly higher survival rate than the TACE-only group (P =
      0.038). Age >=65 years, serum albumin <=35 g/l, and treatment category
      (combination therapy or TACE only) were independent prognostic factors for
      survival according to multivariate analysis. CONCLUSION: The combination of
      (131)I-metuximab and chemoembolization extended survival in patients with
      intermediate HCC compared with TACE only, and was well tolerated by patients with
      Child-Pugh class A or B disease. This combination seems to be a promising
      treatment modality for patients with intermediate HCC.

PMID- 22588628
TI  - Respiratory gated PET/CT in a European multicentre retrospective study: added
      diagnostic value in detection and characterization of lung lesions.
AB  - PURPOSE: The aim of our work is to evaluate the added diagnostic value of
      respiratory gated (4-D) positron emission tomography/computed tomography (PET/CT)
      in lung lesion detection/characterization in a large patient population of a
      multicentre retrospective study. METHODS: The data of 155 patients (89 men, 66
      women, mean age 63.9 +/- 11.1 years) from 5 European centres and submitted to
      standard (3-D) and 4-D PET/CT were retrospectively analysed. Overall, 206 lung
      lesions were considered for the analysis (mean +/- SD lesions dimension 14.7 +/-
      11.8 mm). Maximum standardized uptake values (SUV(max)) and lesion detectability
      were assessed for both 3-D and 4-D PET/CT studies; 3-D and 4-D PET/CT findings
      were compared to clinical follow-up as standard reference. RESULTS: Mean +/- SD 3
      D and 4-D SUV(max) values were 5.2 +/- 5.1 and 6.8 +/- 6.1 (p < 0.0001),
      respectively, with an average percentage increase of 30.8 %. In 3-D PET/CT, 86 of
      206 (41.7 %) lesions were considered positive, 70 of 206 (34 %) negative and 50
      of 206 (24.3 %) equivocal, while in 4-D PET/CT 117 of 206 (56.8 %) lesions were
      defined as positive, 80 of 206 (38.8 %) negative and 9 of 206 (4.4 %) equivocal.
      In 34 of 50 (68 %) 3-D equivocal lesions follow-up data were available and the
      presence of malignancy was confirmed in 21 of 34 (61.8 %) lesions, while in 13 of
      34 (38.2 %) was excluded. In 31 of these 34 controlled lesions, 20 of 34 (58.8 %)
      and 11 of 34 (32.4 %) were correctly classified by 4-D PET/CT as positive and
      negative, respectively; 3 of 34 (8.8 %) remained equivocal. With equivocal
      lesions classified as positive, the overall accuracy of 3-D and 4-D was 85.7 and
      92.8 %, respectively, while the same figures were 80.5 and 94.2 % when equivocal
      lesions were classified as negative. CONCLUSION: The respiratory gated PET/CT
      technique is a valuable clinical tool in diagnosing lung lesions, improving
      quantification and confidence in reporting, reducing 3-D undetermined findings
      and increasing the overall accuracy in lung lesion detection and
      characterization.

PMID- 22588629
TI  - Anti-nociceptive and anti-inflammatory effects of cyanocobalamin (vitamin B12)
      against acute and chronic pain and inflammation in mice.
AB  - In this study, the anti-nociceptive and anti-inflammatory effects of
      cyanocobalamin (Vit B12) against acute and chronic pain and inflammation were
      evaluated in mice. Vit B12 (0.87, 1 and 1.77 mg/kg) were injected
      intraperitoneally. The anti-nociceptive effects against acute pain were examined
      using hot-plate and writhing tests. The chronic pain was examined 14 days after
      sciatic nerve ligation using the hot-plate test. Morphine (10 mg/kg) was used as
      a positive control. Anti-inflammatory effects of Vit B12 against acute and
      chronic inflammation were assessed using xylene-induced edema in ears and
      granuloma caused by compressed cotton implantation, respectively. In these tests,
      sodium diclofenac (15 mg/kg) was used as a positive control. Vit B12 showed a
      dose related effect in acute anti-nociceptive test and increased the anti
      nociceptive effect of morphine in chronic treatment. Vit B12 demonstrated an anti
      nociceptive effect in chronic studies as single or continues daily treatment and
      increased significantly the anti-nociceptive effect of morphine. All doses of Vit
      B12 significantly decreased xylene-induced ear edema. Maximum anti-inflammatory
      effect (37.5%) was obtained at dose of 1 mg/kg. In chronic inflammation, Vit B12
      significantly decreased granuloma formation in mice. In conclusion our work
      presents some experimental evidence supporting the administration of
      cyanocobalamin in controlling acute and chronic neuropathic pain. Cyanocobalamin
      may have anti-inflammatory effect. It may reduce tolerance to anti-nociceptive
      effect of morphine as well.

PMID- 22588630
TI  - In vitro and in vivo evaluation of Triptolide-loaded pluronic P105 polymeric
      micelles.
AB  - Thin film method was applied successfully to prepare Triptolide (TP)-loaded
      micelles system. With a dynamic light scattering sizer and a transmission
      electron microscopy, it was shown that the TP-loaded micelles had a mean size of
      84.3+/-6.4 nm with a spherical shape. The in vitro release profiles indicated
      that the release of TP from the micelles exhibited a sustained release behavior.
      A similar phenomenon was also observed in a pharmacokinetic study in rats, in
      which AUC of the micelles formulation were 4.7-fold higher than that of TP
      injection. The biodistribution study in rats showed that the TP-loaded micelles
      not only decreased drug uptake by liver, but also increased distribution of drug
      in ovary. The present work demonstrated the feasibility of controlled delivery of
      TP utilizing micelles system.

PMID- 22588631
TI  - Synthesis and biological activities of some 1,3-benzoxazol-2(3H)-one derivatives
      as anti-quorum sensing agents.
AB  - Antibiotics are commonly used to treat microbial infections. Due to misuse or
      large-scale use of antibiotics, many pathogens have gained resistance which makes
      antibiotic treatments ineffective. The discovery that many bacteria use quorum
      sensing (QS) to regulate their virulence factor and pathogenicity production
      makes the QS system an attractive target for antimicrobial therapy. A series of
      1,3-benzoxazol-2(3H)-one derivatives were designed and synthesized as QS
      inhibitors (QSIs) and tested for their QS inhibitory activities. In vitro quorum
      sensing inhibitor screen (QSIS) assay indicated that the 1,3-benzoxazol-2(3H)-one
      (compound 1), 5-chloro-1,3-benzoxazol-2(3H)-one (compound 6), 6-methyl-1,3
      benzoxazol-2(3H)-one (compound 11), and 5-methyl-1,3-benzoxazol-2(3H)-one
      (compound 16), inhibit QS system in quorum sensing selector (QSIS)1 strain. These
      4 QSIs also significantly reduced elastase production, biofilm formation and
      swarming motility of Pseudomonas aeruginosa PA01 strain. These results suggest
      that compound 1, 6, 11 and 16 may provide a starting point for the design and
      development of new anti-pathogenic drugs that restrict virulence of P. aeruginosa
      and possibly other clinically important human pathogens. In addition, these QSI
      molecules could potentially be used in combination with conventional antibiotics
      to increase the efficiency of disease control and to extend the life span of
      established antimicrobials.

PMID- 22588632
TI  - Incorporating insect infestation into rodent seed dispersal: better if the larva
      is still inside.
AB  - Many nutritious seeds are commonly attacked by insects which feed on the seed
      reserves. However, studies have not fully explored the ecological implications of
      insect infestation in animal seed dispersal and subsequent plant regeneration.
      Our question is whether the fact that an infested seed still contains the larva
      or not might increase/decrease the probability of being successfully dispersed by
      animals. This study examines the effects of weevil-infested seeds on the natural
      regeneration of a rodent-dispersed oak species. Rodents showed a high ability to
      discriminate between sound and infested seeds, even when the larva was still
      inside. As a result, rodents caused differential seed dispersal for sound and
      infested seeds by modifying multiple aspects of the dispersal process. We found
      that, for the same seed weight, infested acorns with a larva still inside can
      contribute to natural regeneration (0.7 % of seedlings in next summer), although
      in comparison to sound acorns they suffered higher predation rates by rodents
      (both partial and complete), were removed later from the ground (less preferred),
      cached less frequently, and dispersed to shorter distances, which reduced their
      potential to colonize new environments. However, infested seeds with exit holes
      are notably less preferred by rodents and, when dispersed, they are mostly
      deposited on the litter (uncached) with shorter dispersal distances and lower
      emergence success. Thus, the probability that larval-holed acorns will produce
      viable seedlings is extremely low (null in this study). Whether infested seeds
      still contain a larva or not clearly determines the probability of being
      successfully dispersed. Premature seed drop prolongs the presence of the larva
      inside the acorn after seed drop, and could be a possible mechanism to allow
      dispersal of infested seeds.

PMID- 22588633
TI  - High urban population density of birds reflects their timing of urbanization.
AB  - Living organisms generally occur at the highest population density in the most
      suitable habitat. Therefore, invasion of and adaptation to novel habitats imply a
      gradual increase in population density, from that at or below what was found in
      the ancestral habitat to a density that may reach higher levels in the novel
      habitat following adaptation to that habitat. We tested this prediction of
      invasion biology by analyzing data on population density of breeding birds in
      their ancestral rural habitats and in matched nearby urban habitats that have
      been colonized recently across a continental latitudinal gradient. We estimated
      population density in the two types of habitats using extensive point census bird
      counts, and we obtained information on the year of urbanization when population
      density in urban habitats reached levels higher than that of the ancestral rural
      habitat from published records and estimates by experienced ornithologists. Both
      the difference in population density between urban and rural habitats and the
      year of urbanization were significantly repeatable when analyzing multiple
      populations of the same species across Europe. Population density was on average
      30 % higher in urban than in rural habitats, although density reached as much as
      100-fold higher in urban habitats in some species. Invasive urban bird species
      that colonized urban environments over a long period achieved the largest
      increases in population density compared to their ancestral rural habitats. This
      was independent of whether species were anciently or recently urbanized,
      providing a unique cross-validation of timing of urban invasions. These results
      suggest that successful invasion of urban habitats was associated with gradual
      adaptation to these habitats as shown by a significant increase in population
      density in urban habitats over time.

PMID- 22588634
TI  - Determinants of dietary lignan intake in a representative sample of young
      Spaniards: association with lower obesity prevalence among boys but not girls.
AB  - BACKGROUND/OBJECTIVES: Lignan-rich diets have been associated with favorable
      health effects through improved metabolic profile. In this study, we hypothesized
      that dietary lignan intake could be also associated with childhood obesity.
      SUBJECTS/METHODS: We studied prevalent obesity in relation to lignan intake
      within the enKid study that involved 3438 children, adolescents and young adults
      (2-24 years old). Participant's dietary records were used to calculate lignan
      dietary intake using a lignan composition database adapted to the Spanish diet.
      RESULTS: The mean intake of the dietary lignans was calculated as ~1 mg/day,
      corresponding mainly (37%) to pinoresinol. No gender differences were found, but
      lignan intake was positively associated with age, physical activity level and
      dietary fiber intake, and negatively with the intake of polyunsaturated and
      saturated fatty acids. The main sources of dietary lignans were refined wheat,
      olive oil and whole-wheat bread. A strong association between dietary lignan
      intake and prevalent obesity was found only for boys, with odds ratio (highest
      versus lowest quartile of lignan intake) of 0.34 (95% confidence interval, 0.17
      0.70) after adjusting for main confounders, including dietary fiber. CONCLUSIONS:
      Boys with the highest lignan-rich products including cereals, whole-grain
      products and olive oil, presented less cases of obesity in this representative
      sample of Spanish children and adolescents. It is unknown whether this
      association implies an active role of dietary lignans on obesity development, or
      is merely an indicator of a healthier lifestyle.

PMID- 22588636
TI  - GUT bacteria and aspartame: why are we surprised?

PMID- 22588635
TI  - Effects of different fractions of whey protein on postprandial lipid and hormone
      responses in type 2 diabetes.
AB  - BACKGROUND/OBJECTIVES: Exacerbated postprandial lipid responses are associated
      with an increased cardiovascular risk. Dietary proteins influence postprandial
      lipemia differently, and whey protein has a preferential lipid-lowering effect.
      We compared the effects of different whey protein fractions on postprandial lipid
      and hormone responses added to a high-fat meal in type 2 diabetic subjects.
      SUBJECTS/METHODS: A total of 12 type 2 diabetic subjects ingested four isocaloric
      test meals in randomized order. The test meals contained 100 g of butter and 45 g
      of carbohydrate in combination with 45 g of whey isolate (iso-meal), whey
      hydrolysate (hydro-meal), alpha-lactalbumin enhanced whey (lac-meal) or
      caseinoglycomacropeptide enhanced whey (CGMP-meal). Plasma concentrations of
      triglyceride, retinyl palmitate, free fatty acid, insulin, glucose, glucagon,
      glucagon-like peptide 1 and glucose-dependent insulinotropic peptide were
      measured before and at regular intervals until 8-h postprandially. RESULTS: We
      found no statistical significant differences between meals on our primary
      variable triglyceride. The retinyl palmitate response was higher after the hydro
      meal than after the iso- and lac-meal in the chylomicron-rich fraction (P=0.008)
      while no significant differences were found in the chylomicron-poor fraction. The
      hydro- and iso-meal produced a higher insulin response compared with the lac- and
      CGMP-meal (P<0.001). Otherwise no significant differences in the hormone
      responses were found in the incremental area under the curve over the 480-min
      period. CONCLUSIONS: A supplement of four different whey protein fractions to a
      fat-rich meal had similar effects on postprandial triglyceride responses in type
      2 diabetic subjects. Whey isolate and whey hydrolysate caused a higher insulin
      response.

PMID- 22588638
TI  - Trends in methanol decomposition on transition metal alloy clusters from scaling
      and Bronsted-Evans-Polanyi relationships.
AB  - A combination of first principles Density Functional Theory calculations and
      thermochemical scaling relationships are employed to estimate the thermochemistry
      and kinetics of methanol decomposition on unsupported subnanometer metal
      clusters. The approach uses binding energies of various atomic and molecular
      species, determined on the pure metal clusters, to develop scaling relationships
      that are then further used to estimate the methanol decomposition thermodynamics
      for a series of pure and bimetallic clusters with four atoms per cluster.
      Additionally, activation energy barriers are estimated from Bronsted-Evans
      Polanyi plots relating transition and final state energies on these clusters. The
      energetic results are combined with a simple, microkinetically-inspired rate
      expression to estimate reaction rates as a function of important catalytic
      descriptors, including the carbon and atomic oxygen binding energies to the
      clusters. Based on these analyses, several alloy clusters are identified as
      promising candidates for the methanol decomposition reaction. 

PMID- 22588639
TI  - Transcranial magnetic stimulation combined with physiotherapy in rehabilitation
      of poststroke hemiparesis: a randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: Low-frequency repetitive transcranial magnetic stimulation (rTMS) of
      the contralesional primary motor cortex (M1) may improve recovery in patients
      with hemiparetic stroke. OBJECTIVE: To evaluate the effectiveness of applying 1
      Hz rTMS to the contralesional M1 in addition to physiotherapy during early
      rehabilitation for stroke patients with hand hemiparesis in a randomized, sham
      controlled, double-blind study. METHODS: Forty patients with moderate upper
      extremity hemiparesis were randomized to receive 3 weeks of motor training (45
      minutes daily) preceded by 30 minutes of 1 Hz rTMS applied to the contralesional
      M1 or 30 minutes of sham rTMS. Functional assessment of the paretic hand using
      the Wolf Motor Function Test was performed before, immediately after, and 3
      months after completing treatment. RESULTS: No statistically significant
      differences were found between the experimental and the control group for hand
      function (Wolf Motor Function Test; P = .92) or the level of neurological deficit
      (National Institutes of Health Stroke Scale [NIHSS]; P = .82) after treatment.
      Effect sizes for the experimental (d = 0.5) and the control group (d = 0.47) were
      small. Similar results were observed at the 3-month follow-up. CONCLUSIONS: The
      findings did not suggest that rTMS suppression of the contralesional motor cortex
      augments the effect of early neurorehabilitation for upper limb hemiparesis.
      Larger trials that stratify subjects based on residual motor function or
      physiological measures of excitation and inhibition may identify responders in
      the future.

PMID- 22588637
TI  - Persistence of the effect of birth size on dysglycaemia and type 2 diabetes in
      old age: AGES-Reykjavik Study.
AB  - We studied the effect of birth size on glucose and insulin metabolism among old
      non-diabetic individuals. We also explored the combined effect of birth size and
      midlife body mass index (BMI) on type 2 diabetes in old age. Our study comprised
      1,682 Icelanders whose birth records included anthropometrical data. The same
      individuals had participated in the prospective population-based Reykjavik Study,
      where BMI was assessed at a mean age of 47 years, and in the AGES-Reykjavik Study
      during 2002 to 2006, where fasting glucose, insulin and HbA1c were measured and
      homeostasis model assessment for the degree of insulin resistance (HOMA-IR)
      calculated at a mean age of 75.5 years. Type 2 diabetes was determined as having
      a history of diabetes, using glucose-modifying medication or fasting glucose of
      >7.0 mmol/l. Of the participants, 249 had prevalent type 2 diabetes in old age.
      Lower birth weight and body length were associated with higher fasting glucose,
      insulin, HOMA-IR and HbA1c among old non-diabetic individuals. Higher birth
      weight and ponderal index at birth decreased the risk for type 2 diabetes in old
      age, odds ratio (OR), 0.61 [95 % confidence interval (CI), 0.48-0.79] and 0.96
      (95 % CI, 0.92-1.00), respectively. Compared with those with high birth weight
      and low BMI in midlife, the odds of diabetes was almost five-fold for individuals
      with low birth weight and high BMI (OR, 4.93; 95 % CI, 2.14-11.37). Excessive
      weight gain in adulthood might be particularly detrimental to the health of old
      individuals with low birth weight.

PMID- 22588640
TI  - Glutathione mediated reductive activation and mitochondrial dysfunction play key
      roles in lithium induced oxidative stress and cytotoxicity in liver.
AB  - Lithium preparations are commonly used drug in treating mental disorders and
      bipolar diseases, but metal's cytotoxic mechanisms have not yet been completely
      understood. In this study, we investigated the cytotoxic mechanisms of lithium in
      freshly isolated rat hepatocytes. Lithium cytotoxicity were associated with
      reactive oxygen species (ROS) formation and collapse of mitochondrial membrane
      potential and cytochrome c release into the hepatocyte cytosol. All of the
      mentioned lithium-induced cytotoxicity markers were significantly (P < 0.05)
      prevented by ROS scavengers, antioxidants, mitochondrial permeability transition
      pore sealing agents and adenosine triphosphate generators. Hepatocyte glutathione
      (GSH) was also rapidly oxidized and GSH-depleted hepatocytes were more resistant
      to lithium-induced oxidative stress markers. This suggests that lithium is
      activated by GSH. Our results also showed that CYP2E1 is involved in lithium
      oxidative stress mechanism. Lithium cytotoxicity was also associated with
      mitochondrial injuries initiated by increased ROS formation resulted from metal
      CYP2E1 destructive interaction or metal-induced disruption of mitochondrial
      electron transfer chain. Methyl donors such as betaine, methionine, or folic acid
      prevented lithium cytotoxicity, and this suggests that this metal is detoxified
      by phase II metabolic methylation. In conclusion lithium-induced cytotoxicity
      could be attributed to oxidative stress and mitochondrial dysfunction.

PMID- 22588641
TI  - An introduction to parasitic wasps of Drosophila and the antiparasite immune
      response.
AB  - Most known parasitoid wasp species attack the larval or pupal stages of
      Drosophila. While Trichopria drosophilae infect the pupal stages of the host
      (Fig. 1A-C), females of the genus Leptopilina (Fig. 1D, 1F, 1G) and Ganaspis
      (Fig. 1E) attack the larval stages. We use these parasites to study the molecular
      basis of a biological arms race. Parasitic wasps have tremendous value as
      biocontrol agents. Most of them carry virulence and other factors that modify
      host physiology and immunity. Analysis of Drosophila wasps is providing insights
      into how species-specific interactions shape the genetic structures of natural
      communities. These studies also serve as a model for understanding the hosts'
      immune physiology and how coordinated immune reactions are thwarted by this class
      of parasites. The larval/pupal cuticle serves as the first line of defense. The
      wasp ovipositor is a sharp needle-like structure that efficiently delivers eggs
      into the host hemocoel. Oviposition is followed by a wound healing reaction at
      the cuticle (Fig. 1C, arrowheads). Some wasps can insert two or more eggs into
      the same host, although the development of only one egg succeeds. Supernumerary
      eggs or developing larvae are eliminated by a process that is not yet understood.
      These wasps are therefore referred to as solitary parasitoids. Depending on the
      fly strain and the wasp species, the wasp egg has one of two fates. It is either
      encapsulated, so that its development is blocked (host emerges; Fig. 2 left); or
      the wasp egg hatches, develops, molts, and grows into an adult (wasp emerges;
      Fig. 2 right). L. heterotoma is one of the best-studied species of Drosophila
      parasitic wasps. It is a "generalist," which means that it can utilize most
      Drosophila species as hosts. L. heterotoma and L. victoriae are sister species
      and they produce virus-like particles that actively interfere with the
      encapsulation response. Unlike L. heterotoma, L. boulardi is a specialist
      parasite and the range of Drosophila species it utilizes is relatively limited.
      Strains of L. boulardi also produce virus-like particles although they differ
      significantly in their ability to succeed on D. melanogaster. Some of these L.
      boulardi strains are difficult to grow on D. melanogaster as the fly host
      frequently succeeds in encapsulating their eggs. Thus, it is important to have
      the knowledge of both partners in specific experimental protocols. In addition to
      barrier tissues (cuticle, gut and trachea), Drosophila larvae have systemic
      cellular and humoral immune responses that arise from functions of blood cells
      and the fat body, respectively. Oviposition by L. boulardi activates both immune
      arms. Blood cells are found in circulation, in sessile populations under the
      segmented cuticle, and in the lymph gland. The lymph gland is a small
      hematopoietic organ on the dorsal side of the larva. Clusters of hematopoietic
      cells, called lobes, are arranged segmentally in pairs along the dorsal vessel
      that runs along the anterior-posterior axis of the animal (Fig. 3A). The fat body
      is a large multifunctional organ (Fig. 3B). It secretes antimicrobial peptides in
      response to microbial and metazoan infections. Wasp infection activates immune
      signaling (Fig. 4). At the cellular level, it triggers division and
      differentiation of blood cells. In self defense, aggregates and capsules develop
      in the hemocoel of infected animals (Fig. 5). Activated blood cells migrate
      toward the wasp egg (or wasp larva) and begin to form a capsule around it (Fig.
      5A-F). Some blood cells aggregate to form nodules (Fig. 5G-H). Careful analysis
      reveals that wasp infection induces the anterior-most lymph gland lobes to
      disperse at their peripheries (Fig. 6C, D). We present representative data with
      Toll signal transduction pathway components Dorsal and Spatzle (Figs. 4,5,7), and
      its target Drosomycin (Fig. 6), to illustrate how specific changes in the lymph
      gland and hemocoel can be studied after wasp infection. The dissection protocols
      described here also yield the wasp eggs (or developing stages of wasps) from the
      host hemolymph (Fig. 8).

PMID- 22588642
TI  - Transoral robotic surgery and adjuvant therapy for oropharyngeal carcinomas and
      the influence of p16 INK4a on treatment outcomes.
AB  - OBJECTIVES/HYPOTHESIS: To determine the prognostic influence of p16(INK4a)
      immunohistochemistry on the survival of resectable oropharyngeal carcinomas
      (OPSCC). STUDY DESIGN: Retrospective pathologic evaluation of a prospective
      single-arm cohort study at a tertiary referral center. METHODS: There were 48
      patients with resectable OPSCC who consented for transoral robotic surgery (TORS)
      and banked tissue specimen for assessment. TORS was with or without adjuvant
      radiation or chemoradiation. Main outcome measures were p16(INK4a) status, human
      papillomavirus status, local-regional disease control, and overall, disease
      specific, and disease-free survival. RESULTS: p16(INK4a) and HPV positivity were
      identified in 73% and 74% of patients respectively. With a median follow-up of
      38.8 months (2.5-63.3 months), only one local-regional relapse has occurred in
      both the p16(INK4a)-positive and p16(INK4a) -negative cohorts. No disease
      specific, disease-free, and overall survival differences were observed between
      p16(INK4a) -positive and p16(INK4a)-negative patients (P = .446, P = .277, P =
      .643, respectively). CONCLUSIONS: p16(INK4a) was not prognostic in resectable
      OPSCC when treated with an initial TORS approach.

PMID- 22588645
TI  - Anterior pelvic organ prolapse repair using synthetic mesh.
AB  - Since the U.S. Food and Drug Administration (FDA) statement on mesh in July of
      2011, there has been controversy regarding synthetic mesh repairs for vaginal
      prolapse. In this article, we review the biochemical basis for the use of
      synthetic mesh in prolapse repair as well as clinical results of anterior
      compartment prolapse repair with synthetic mesh. Finally, we discuss the FDA
      warning regarding mesh.

PMID- 22588644
TI  - Physiologically based pharmacokinetic modeling to investigate regional brain
      distribution kinetics in rats.
AB  - One of the major challenges in the development of central nervous system (CNS)
      targeted drugs is predicting CNS exposure in human from preclinical data. In this
      study, we present a methodology to investigate brain disposition in rats using a
      physiologically based modeling approach aiming at improving the prediction of
      human brain exposure. We specifically focused on quantifying regional diffusion
      and fluid flow processes within the brain. Acetaminophen was used as a test
      compound as it is not subjected to active transport processes. Microdialysis
      probes were implanted in striatum, for sampling brain extracellular fluid (ECF)
      concentrations, and in lateral ventricle (LV) and cisterna magna (CM), for
      sampling cerebrospinal fluid (CSF) concentrations. Serial blood samples were
      taken in parallel. These data, in addition to physiological parameters from
      literature, were used to develop a physiologically based model to describe the
      regional brain pharmacokinetics of acetaminophen. The concentration-time profiles
      of brain ECF, CSF(LV), and CSF(CM) indicate a rapid equilibrium with plasma.
      However, brain ECF concentrations are on average fourfold higher than CSF
      concentrations, with average brain-to-plasma AUC(0-240) ratios of 121%, 28%, and
      35% for brain ECF, CSF(LV), and CSF(CM), respectively. It is concluded that for
      acetaminophen, a model compound for passive transport into, within, and out of
      the brain, differences exist between the brain ECF and the CSF pharmacokinetics.
      The physiologically based pharmacokinetic modeling approach is important, as it
      allowed the prediction of human brain ECF exposure on the basis of human CSF
      concentrations.

PMID- 22588646
TI  - First total synthesis of (+)-indicanone.
AB  - The first total synthesis of the guaiane-type sesquiterpene, (+)-indicanone (1),
      isolated from the root of Wikstroemia indica, was accomplished based on the
      rhodium(I)-catalyzed Pauson-Khand-type reaction of the allenyne derivative, which
      was derived from (+)-limonene. This total synthesis unambiguously confirmed the
      complete structure of (+)-indicanone involving its absolute stereochemistry.

PMID- 22588647
TI  - Predictors of health-related quality of life and fatigue in systemic sclerosis:
      evaluation of the EuroQol-5D and FACIT-F assessment tools.
AB  - This study evaluates predictors of health-related quality of life (HRQoL) and
      fatigue in systemic sclerosis (SSc) using two novel self-report indices. A cross
      sectional study of patients with SSc was undertaken using a postal questionnaire
      including the EuroQol-5Domain health questionnaire (EQ-5DTM), Functional
      Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F) and the Scleroderma
      Health Assessment Questionnaire (SHAQ). The EQ-5D assesses five domains of health
      quality and is quantified as a time trade-off (TTO) value and patient global
      assessment (0-100 visual analogue scale [VAS]). The FACIT-F is a 13-item
      questionnaire (0-52 scale). Higher scores for both the EQ-5D and FACIT-F indicate
      better health. Case notes were scrutinised for patient demographics, disease
      duration, serology and clinical phenotype. Sixty-eight patients (60 females, mean
      age 62.6 years) completed the questionnaires. Fatigue correlated closely with
      HRQoL (r (s) = 0.78 and 0.77 for FACIT-F vs. EQ-5D VAS and TTO respectively, p <
      0.01) and disability (r (s) = -0.74 for FACIT-F vs. HAQ-DI, p < 0.01). Pain was
      the most frequently reported health problem (80 %) in the EQ-5D. HRQoL also
      correlated closely with disability (r (s) = 0.83 for EQ-5D vs. HAQ-DI, p < 0.01).
      SHAQ-VAS scores correlated well with the FACIT-F, EQ-5D and HAQ-DI scores (p <
      0.05 for all comparisons). Of the patient demographics and clinical disease
      associations, only the absence of upper gastrointestinal complications was
      associated with better levels of fatigue, HRQoL and function. There is a strong
      correlation between disability, fatigue and HRQoL measured using self-reports,
      possibly reflecting similarly perceived health beliefs amongst patients across
      outcomes. There was little association between self-report indices and patient
      demographics and/or clinical phenotype.

PMID- 22588648
TI  - Combining a peptide vaccine with oral ingestion of Lentinula edodes mycelia
      extract enhances anti-tumor activity in B16 melanoma-bearing mice.
AB  - New anticancer vaccines must overcome regulatory T cell (Treg)-mediated
      immunosuppression. We previously reported that oral ingestion of Lentinula edodes
      mycelia (L.E.M.) extract restores melanoma-reactive T cells in melanoma-bearing
      mice via a mitigation of Treg-mediated immunosuppression. In this study, we
      investigated the effect of oral ingestion of the extract on peptide vaccine
      induced anti-tumor activity. The day after subcutaneous inoculation in the
      footpad with B16 melanoma, mice were freely fed the extract and were vaccinated
      with a tyrosinase-related protein 2(180-188) peptide. The peptide vaccine was
      repeated thrice weekly. Melanoma growth was significantly suppressed in mice
      treated with both the peptide vaccine and L.E.M. extract compared with mice
      treated with vaccine or extract alone, and the effect was CD8(+) T cell
      dependent. The combination therapy increased H-2K(b)-restricted and B16 melanoma
      reactive T cells in the draining lymph nodes and spleen. Flow cytometric and
      immunohistological analyses revealed that the combination therapy significantly
      decreased the percentage of Tregs in the draining lymph nodes and spleen of
      melanoma-bearing mice compared to treatment with vaccine or extract alone.
      Kinetic analyses of peptide-specific T cells and Tregs revealed that induction of
      peptide-specific T cells by the peptide vaccine alone was transient, but when
      combined with L.E.M. extract, it efficiently prolonged the duration of peptide
      specific T cell induction without increasing the percentage of Tregs. These
      results indicate that combination therapy enhances peptide vaccine-induced anti
      tumor activity due to attenuation of the increase in the percentage of Tregs in
      tumor-bearing hosts.

PMID- 22588649
TI  - HLA-DRB1*1501 and HLA-DQB1*0301 alleles are positively associated with HPV16
      infection-related Kazakh esophageal squamous cell carcinoma in Xinjiang China.
AB  - Multiple determinant factors are involved in the occurrence and progression of
      esophageal squamous cell carcinoma (ESCC). Human papillomavirus (HPV) and human
      leukocyte antigen (HLA) polymorphism were identified as important factors. This
      study examined the associations between the development of Kazakh ESCC and the
      determinant factors including HLA-DRB1*0901, 1501; DQB1*0301, 0602; high-risk HPV
      infection in the area of Xinjiang, China. 200 Kazakh patients with ESCC and 150
      controls were recruited, and polymerase chain reaction (PCR) was performed to
      detect HLA-DRB1*0901, 1501 and DQB1*0301,0602 using sequence-specific primers
      (SSPs). HPV16 was detected in esophageal specimens using PCR. HPV16 infection
      rate in Kazakh ESCC case group was 41 %, significantly higher than that of
      control group 14 % (OR = 3.62; 95 % CI, 2.15-6.09; P < 0.001). A positive
      association between ESCC and HLA-DRB1*1501 (OR = 2.46, P < 0.0125) or HLA
      DQB1*0301 (OR = 3.34, P < 0.0125) alleles was observed. Similar tendencies were
      observed for HLA-DRB1*1501 (OR = 3.095, P < 0.0125) and HLA-DQB1*0301 (OR =
      2.410, P < 0.0125) alleles with HPV16-positive ESCC. HLA-DRB1*1501, HLA-DQB1*0301
      and DQB1*0602 were significantly associated with ESCC when the age was >=55 years
      (P < 0.0125 for all), whereas only HLA-DQB1*0301 was significantly associated
      with ESCC when the age was <55 years (P < 0.0125). HLA-DRB1*1501 and HLA
      DQB1*0301 were significantly associated with an increase in ESCC occurrence in
      females (P < 0.0125), whereas only HLA-DQB1*0301 was significantly associated
      with ESCC in males. Moreover, the occurrence of HLA-DQB1*0602 gene in poorly
      differentiated ESCC group (68.8 %) was slightly higher than that of well
      differentiated squamous cell carcinoma group (31.2 %). The difference was not
      statistically significant (P > 0.0125). The study suggests that HLA-DRB1*1501 and
      HLA-DQB1*0301 may influence the immune response to specific tumor and HPV-encoded
      epitopes and affect the risk of Kazakh ESCC in XinJiang, China.

PMID- 22588650
TI  - Bench testing of a new hyperbaric chamber ventilator at different atmospheric
      pressures.
AB  - PURPOSE: Providing mechanical ventilation is challenging at supra-atmospheric
      pressure. The higher gas density increases resistance, reducing the flow
      delivered by the ventilator. A new hyperbaric ventilator (Siaretron IPER 1000) is
      said to compensate for these effects automatically. The aim of this bench test
      study was to validate the compensation, define its limits and provide details on
      the ventilator's output at varied atmospheric pressures. METHODS: Experiments
      were conducted inside a multiplace hyperbaric chamber at 1, 2.2, 2.8 and 4
      atmospheres absolute (ATA), with the ventilator connected to a test lung.
      Transducers were recalibrated at each ATA level. Various ventilator settings were
      tested in volume and pressure control modes. Measured tidal volumes were compared
      with theoretical predictions based on gas laws. RESULTS: Results confirmed the
      ventilator's ability to provide compensation, but also identified its limits. The
      compensation range could be predicted and depended on the maximal flow
      attainable, decreasing linearly with increasing atmospheric pressure. With
      settings inside the range, tidal volumes approximated set values (mean error 10
      +/- 5 %). With settings outside the range, the volume was limited to the
      predicted maximal value calculated from maximal flow. A practical guide for
      clinicians is provided. CONCLUSION: The IPER 1000 ventilator attempted to deliver
      stable tidal volume by adjusting the opening of the inspiratory valve in
      proportion to atmospheric pressure. Adequate compensation was observed, albeit
      only within a predictable range, which can be reliably predicted for each setting
      and ATA level combination. Setting a tidal volume outside this range can result
      in an unwanted decrease in minute ventilation.

PMID- 22588651
TI  - Frequency, characteristics, and outcomes of pediatric patients readmitted to the
      cardiac critical care unit.
AB  - PURPOSE: To describe the characteristics and outcomes of patients readmitted to a
      pediatric cardiac critical care unit (CCCU) from the ward within 72 h of their
      first discharge. METHODS: This was a retrospective analysis of data collected on
      patients admitted to the CCCU between January 1, 2000 and January 31, 2007. The
      setting was an 18-bed pediatric CCCU in a tertiary care university hospital. No
      interventions were performed. RESULTS: Among the 4,625 patients admitted to the
      CCCU, 112 (2.4 %) were readmitted from the ward within 72 h of their discharge.
      The most common cause for readmission was respiratory symptoms (42.9 %).
      Significant changes in the chest X-ray prior to discharge were identified
      retrospectively in 12.5 % of these patients. Cardiovascular symptoms were
      similarly frequent (40.2 %) among these patients. Nine (8 %) of the patients died
      during the readmission period, a rate which is considerably higher than the
      overall CCCU mortality rate (3.8 %) in the same period of time. CONCLUSIONS:
      Respiratory reasons are the most common cause for early CCCU readmission among
      pediatric cardiac patients. The readmitted patients have higher rates of death
      compared to the overall pediatric cardiac critical care population. The
      development of objective predischarge scores might help planning appropriately
      for discharge to the ward and avoid readmission to the CCU.

PMID- 22588652
TI  - [Intensive care - the challenges rise].

PMID- 22588653
TI  - [Percutaneous coronary intervention in a patient with  acute myeloid leukemia].
AB  - HISTORY AND ADMISSION FINDINGS: A 63-year-old woman was referred to our hospital
      for evaluation of leukocytopenia and blast cells in the peripheral blood smear.
      The general condition was reduced, a maculo-papulous exanthema of the face and
      upper body as well as a general lymphadenopathy were found. INVESTIGATIONS: Bone
      marrow examination revealed the diagnosis of acute myeloid leukemia (AML) FAB M1
      and a normal karyotype. Extramedullary manifestations of AML were demonstrated in
      skin and lymphnode biopsies. ECG showed no signs of ischemia, echocardiography a
      normal left-ventricular function. TREATMENT AND COURSE: The patient received
      induction treatment using sequential high-dose cytosinarabinosid and
      mitoxantrone, which rapidly resolved the extramedullary skin- and lymphnode
      manifestations of the AML. During the chemotherapy-associated bone marrow aplasia
      a non-ST-elevation infarction (NSTEMI) developed combined with severe ischemic
      cardiomyopathy, high-grade mitral valve deficiency and serious congestive heart
      failure with respiratory failure. Coronary artery angiography showed a complete
      occlusion of the proximal ramus circumflexus. Percutanous coronary intervention
      (PCI) with implantation of a bare-metal stent was performed, which resulted in
      prompt improvement of the condition. Despite the transfusion-dependent
      thrombocytopenia a dual antiplatelet therapy with acetylsalicylic acid and
      clopidogrel was given. After each unit of platelets transfused a loading dose of
      600 mg clopidogrel was given to prevent stent thrombosis. The patient did not
      experience major bleeding and was discharged in complete remission of AML and
      completely cardially recompensated. CONCLUSION: Coronary angiography and stenting
      can generally be safely performed in patients with transfusion-dependent
      thrombocytopenia. Despite a higher risk of bleeding an oral dual antiplatelet
      therapy with aspirin and e. g. clopidogrel according to the guidelines should be
      performed, but its duration should be adapted to the individual patient
      circumstances.

PMID- 22588654
TI  - [A case of venlafaxine-induced syndrome of inappropriate ADH secretion (SIADH) -
      treatment with tolvaptan].
AB  - HISTORY AND ADMISSION FINDINGS: A 74-year-old woman with known COPD was admitted
      to hospital because of dyspnoa. Clinical and laboratory tests showed an acute
      pulmonary infection which was treated with antibiotics. Additionally she was
      found to have a moderately severe episode of depression for which she had the
      preceding three weeks been treated with venlafaxine, a selective serotonin re
      uptake inhibitor. During the subsequent days she gradually developed a
      hyponatremia with serum sodium levels down to 108 mmol/l. INVESTIGATIONS: After
      excluding common causes of hyponatremia such as a cerebral or pulmonal malignancy
      or endocrine disorders by computed thomography and laboratory tests, a
      venlafaxine induced syndrome of inappropriate ADH secretion (SIADH) was assumed
      to be the cause of the hyponatremia. TREATMENT AND COURSE: As neither
      discontinuation of venlafaxine nor strict fluid restriction led to a rise in the
      natrium level and the patient had a generalized seizure, oral treatment with the
      tolavaptan, a vasopressin-2-receptor antagonist, was initiated. This resulted
      within 48 hours in a rise of the sodium level to 131 mmol/l and there were no
      further seizures. CONCLUSION: Hyponatremia is a relatively common side effect of
      medical treatment with SSRI or SSNRI in elderly patients. The therapy of choice
      in case of a hyponatremia due to a SIADH is to discontinue the antidepressive
      drugs and institute strict fluid restriction. Tolvaptan has recently emerged as a
      promising new therapeutic option for SIADH.

PMID- 22588655
TI  - [Hypercalcemic crisis in intensive care].
AB  - A hypercalcemic crisis is a life-threatening disease with multiorgan failure due
      to severe hypercalcemia. If left untreated, a hypercalcemic crisis is associated
      with a very high mortality and requires immediate diagnostic and therapeutic
      interventions. Especially a rapid rise to high calcium levels impairs the
      function of several organ systems and leads to central nervous, renal,
      cardiovascular and gastrointestinal symptoms. A hypercalcemic crisis is caused in
      more than 90 % by malignancy or primary hyperparathyreoidism and only in very
      rare cases by other diseases such as granulomatous diseases or other
      endocrinological diseases. Causal therapeutic options include an adequate
      treatment of malignancy and a surgical resection of the adenomatous tissue in
      primary hyperparathyreoidism. In addition, an adequate supportive therapy to
      lower calcium levels should be initiated as soon as possible. Rehydration with
      normal saline is the mainstay of therapy. Additional pharmacological therapies
      include biphosphonates, loop diuretics, calcitonin, steroids and calcimimetics.
      Besides classic hemodialysis continous renal replacement therapy with citrate
      anticoagulation is new therapeutical approach that can be used for the acute
      reduction of elevated serum calcium levels.

PMID- 22588656
TI  - [69-year-old patient with dyspnoea after diving].

PMID- 22588657
TI  - [Treatment of inflammatory bowel disease in intensive care medicine].
AB  - In patients with inflammatory bowel disease (IBD) complications of both IBD and
      immunosuppressive therapy may be life-threatening conditions requiring intensive
      care therapy. These patients oftentimes present themselves with severe bloody
      diarrhoea, and infectious colitis, pseudomembranous colitis or intestinal
      ischemia must be included in the differential diagnosis. Steroids,
      immunosuppressants such as azathioprine, 6-mercaptopurine, methotraxate or
      ciclosporine, as well as biologicals, which act as TNF-alpha antagonists, are
      commonly used for maintenance therapy and treatment of acute exacerbations of
      IBD. Due to immunosuppressive therapy potentially life-threatening infections and
      reactivations of latent infections like tuberculosis or cytomegalovirus (CMV) can
      occur. Fistulas, abscesses, perforations and intestinal obstructions are typical
      complications of Crohn's disease in the intensive care setting, whereas clinical
      presentation in ulcerative colitis is characterised by its acute exacerbation and
      the toxic dilatation of the colon, potentially resulting in toxic megacolon with
      high risk of perforation or severe bleeding. Most important for an effective
      therapy in the critically ill patient with inflammatory bowel disease are the
      control of the underlying disease, the empiric antibiotic therapy in case of
      infectious complications, transcutaneous drainage of abscesses, bowel
      decompression in toxic megacolon and the early interdisciplinary assessment of
      the abdomen.

PMID- 22588658
TI  - [Fever of unknown origin in the intensive care unit].
AB  - Fever is common in patients in intensive care units. Sources of fever can be
      infectious or non-infectious. The most common sources of infectious fever include
      ventilator-associated pneumonia, intravascular catheter-related infections,
      infection with Clostridium difficile or sinusitis. Typical examples of non
      infectious fever include thromboembolic events, myocardial infarction, autoimmune
      disease, withdrawal symptoms or a drug-fever. Every new onset of fever prompts
      diagnostic decisions, treatment with antipyretics should be discussed critically.

PMID- 22588659
TI  - [Pharmacotherapy of acute heart failure: update and perspectives].
AB  - In acute decompensated heart failure rapid diagnosis and causal therapy are
      necessary to avoid cardiogenic shock. Treatment goals are to decrease congestion,
      afterload, and neurohormonal activation in order to improve hemodynamics and
      symptoms and, perhaps, reduce in-hospital events, re-hospitalizations, and
      mortality. A combined medical therapy of diuretics and / or vasodilators should
      be favoured in order to protect organs and to avoid toxicities of therapy such as
      hypotension, arrhythmias and renal dysfunction. Intravenous inotropes, such as
      dobutamine and milrinone, should be limited to hypotensive patients with evidence
      of poor tissue perfusion. They improve hemodynamics and organ perfusion but
      result in a higher mortality due to to proarrhythmogenic effects. Therefore, they
      should be given in lowest doses and should be withdrawn as early as possible. A
      preexisting therapy with betablockers should be continued if there is no
      hemodynamic instability. Before demission any patient should be on betablockers
      and ACE inhibitors according to national guidelines resulting in a decrease of re
      hospitalization and mortality rates. New medical therapies should at least
      improve clinical symptoms and favourably reduce re-hospitalization and mortality
      rates.

PMID- 22588660
TI  - [Cholesterol embolism syndrome: a rare, but severe complication in patients with
      atherosclerosis].
AB  - Cholesterol embolization is a serious complication of atherosclerosis. Mainly,
      vascular manipulations during endovascular procedures or vascular surgery can
      release cholesterol crystals from atheromatous plaques. About 20 % are
      spontaneous emboli without precipitating event. The cholesterol crystals are
      distributed by the blood stream, occlude small arteries and induce inflammation.
      Typically, 2 to 6 weeks after a vascular procedure renal failure and
      characteristic cutaneous signs develop. Livedo reticularis and blue toes,
      although classic symptoms, are not pathognomonic and may be even absent.
      Vasculitis is an important differential diagnosis. Diagnosis can only be proven
      by skin, muscle or kidney biopsy. Alternatively, fundoscopy can show retinal
      cholesterol emboli. Therapy is mostly limited to symptomatic measures.
      Corticosteroids have no proven efficacy and may be harmful. Statins should be
      given to all patients due to their plaque stabilizing and anti-inflammatory
      properties. Randomized clinical trials are lacking in this field. Prognosis is
      limited. About 30-55 % patients with renal involvement need renal replacement
      therapy. Mortality is high with 15-30 % of patients dying during the first year.

PMID- 22588661
TI  - Functional genomic methods to study estrogen receptor activity.
AB  - Estrogen Receptor (ER) is a nuclear receptor that mediates the actions of
      estrogen and tamoxifen. ER is expressed in a major fraction of human breast
      cancers. Recently, genomic maps for estrogen- and tamoxifen-ER have been
      published. Interestingly, estrogen and tamoxifen induce similar genomic
      interactions and both ligands have been shown to use co-operating factors. The
      interactions of these co-operating factors within ER regions have impact both on
      ER-DNA interactions and gene expression regulated by estrogen and tamoxifen.
      Moreover, the study of chromatin changes induced by these factors has also
      provided significant insight into our understanding of ER transcriptional
      regulation. This methods review describes some functional genomic methods to
      study the influence of both ER ligands and ER co-operating factors. The analysis
      of protein-DNA interactions and chromatin changes can be explored by using
      classical and novel methods such as Chromatin Immunoprecipitation (ChIP) or
      Formaldehyde-Assisted Isolation of Regulatory Elements (FAIRE). This review also
      explores the properties of each of these methods and the advantages of combining
      them with high throughput sequencing.

PMID- 22588662
TI  - Sphingosine 1-phosphate-primed astrocytes enhance differentiation of neuronal
      progenitor cells.
AB  - Sphingosine 1-phosphate (S1P) is a bioactive signaling lysophospholipid. Effects
      of S1P on proliferation, survival, migration, and differentiation have already
      been described; however, its role as a mediator of interactions between neurons
      and glial cells has been poorly explored. Here we describe effects of S1P, via
      the activation of its receptors in astrocytes, on the differentiation of neural
      progenitor cells (NPC) derived from either embryonic stem cells or the developing
      cerebral cortex. S1P added directly to NPC induced their differentiation, but S1P
      primed astrocytes were able to promote even more pronounced changes in
      maturation, neurite outgrowth, and arborization in NPC. An increase in laminin by
      astrocytes was observed after S1P treatment. The effects of S1P-primed astrocytes
      on neural precursor cells were abrogated by antibodies against laminin. Together,
      our data indicate that S1P-treated astrocytes are able to induce neuronal
      differentiation of NPC by increasing the levels of laminin. These results
      implicate S1P signaling pathways as new targets for understanding neuroglial
      interactions within the central nervous system.

PMID- 22588663
TI  - Improving the diagnosis and treatment of CRPS: insights from a clinical
      immunologist's personal experience with an underrecognized neuroinflammatory
      disorder.
AB  - Complex regional pain syndrome is a neuroinflammatory condition associated with
      overactive glial cells that can be challenging to diagnose and treat. Early
      recognition and treatment are thought to be critical for good outcomes, yet many
      patients experience a delay in diagnosis and have difficulty accessing expert
      medical care. While there are no universally effective treatments, there are
      several promising new therapies, but these are not widely available. Some of the
      specific barriers to diagnosis and treatment are reviewed, with suggestions as to
      how they might be eliminated, leading to better care for all patients with CRPS.

PMID- 22588664
TI  - Genetic investigation of FOXO3A requires special attention due to sequence
      homology with FOXO3B.
AB  - Our study demonstrates that the genetic investigation of forkhead box O3A gene
      (FOXO3A), a validated human longevity gene, is greatly hampered by the fact that
      its exonic regions have 99% sequence homology with the FOXO3B pseudogene. If
      unaccounted for, this high degree of homology can cause serious genotyping or
      sequencing errors. Here, we present an experimental set-up that allows reliable
      data generation for the highly homologous regions and that can be used for the
      evaluation of assay specificity. Using this design, we exemplarily showed FOXO3A
      specific results for two single-nucleotide polymorphisms (SNPs) (rs4945816 and
      rs4946936) that are significantly associated with longevity in our centenarian
      control sample (P(each)=0.0008). Because both SNPs are located in the 3'
      untranslated region of FOXO3A, they could be of functional relevance for the
      longevity phenotype. Our experimental set-up can be used for reliable and
      reproducible data generation for further sequencing and genotyping studies of
      FOXO3A with the aim of discovering new SNPs of functional relevance.

PMID- 22588665
TI  - Association between the 2-bp deletion polymorphism in the duplicated version of
      the alpha7 nicotinic receptor gene and P50 sensory gating.
AB  - There is considerable evidence implicating the 15q13.3 region in neuropsychiatric
      disorders, with the alpha7 nicotinic receptor gene CHRNA7 the most plausible
      candidate. This region has multiple duplications and many copy number variants
      (CNVs). A common CNV involves a partial duplication of CHRNA7 (CHRFAM7A), which
      occurs in either orientation. We examined the distribution of these alternative
      genomic arrangements in a large cohort of psychiatric patients, their relatives
      and controls using the 2-bp deletion polymorphism as a marker for the orientation
      of CHRFAM7A. We investigated three common alleles for association with psychosis
      and with the P50 sensory gating deficit, which is strongly associated with
      psychosis and strongly linked to 15q13.3. We found significant within-family
      association with P50 (empirical P=0.004), which is robust to population
      stratification. Most of the effect came from the 2-bp deletion allele, which tags
      the variant of CHRFAM7A in the same orientation as CHRNA7. This allele is
      associated with the presence of the P50 sensory gating deficit (empirical
      P=0.0006). Tests comparing within-family and between-family components of
      association suggest considerable population stratification in the sample. We
      found no evidence for association with psychosis, but this may reflect lower
      power using this phenotype. Four out of six previous association studies found
      association of different psychiatric phenotypes with the same 2-bp deletion
      allele.

PMID- 22588666
TI  - Clinical utility gene card for: Familial Hypobetalipoproteinaemia (APOB).

PMID- 22588668
TI  - Establishment of cultivating strategy for highly aggregated mycelia of Morchella
      esculenta in a stirred-tank bioreactor.
AB  - Mycelia of Morchella esculenta were found to aggregate rapidly in a submerged
      culture, which caused the decrease in dispersed mycelia and the problem of
      diffusion limitation. The effect of different agitation schemes on the growth of
      mycelia was investigated in a stirred-tank bioreactor. At the constant speed of
      100 or 300 rpm, rapid aggregation caused the biomass concentration to drop to
      zero in 30 h, which was even worse than achieved under static culture.
      Intermittent agitation maintained a higher mycelium fragment concentration for 48
      h and enhanced the biomass concentration to 4.73 g/L at 120 h. The operation with
      a polytron connection disrupted effectively mycelium aggregation, thus increasing
      the specific growth rate, biomass concentration and maximum productivity to
      0.0613 1/h, 7.73 g/L and 0.0878 g/L h at 88 h, respectively. Moreover, logistic
      equations and genetic algorithm (GA) were used for the simulation of biomass
      growth and estimation of all kinetic coefficients. The operating strategy
      developed in this study could be used for the production of highly aggregated
      mycelia, which could also achieve a high cell-density culture in a stirred tank
      reactor.

PMID- 22588667
TI  - Distinguishing the co-ancestries of haplogroup G Y-chromosomes in the populations
      of Europe and the Caucasus.
AB  - Haplogroup G, together with J2 clades, has been associated with the spread of
      agriculture, especially in the European context. However, interpretations based
      on simple haplogroup frequency clines do not recognize underlying patterns of
      genetic diversification. Although progress has been recently made in resolving
      the haplogroup G phylogeny, a comprehensive survey of the geographic distribution
      patterns of the significant sub-clades of this haplogroup has not been conducted
      yet. Here we present the haplogroup frequency distribution and STR variation of
      16 informative G sub-clades by evaluating 1472 haplogroup G chromosomes belonging
      to 98 populations ranging from Europe to Pakistan. Although no basal G-M201*
      chromosomes were detected in our data set, the homeland of this haplogroup has
      been estimated to be somewhere nearby eastern Anatolia, Armenia or western Iran,
      the only areas characterized by the co-presence of deep basal branches as well as
      the occurrence of high sub-haplogroup diversity. The P303 SNP defines the most
      frequent and widespread G sub-haplogroup. However, its sub-clades have more
      localized distribution with the U1-defined branch largely restricted to
      Near/Middle Eastern and the Caucasus, whereas L497 lineages essentially occur in
      Europe where they likely originated. In contrast, the only U1 representative in
      Europe is the G-M527 lineage whose distribution pattern is consistent with
      regions of Greek colonization. No clinal patterns were detected suggesting that
      the distributions are rather indicative of isolation by distance and demographic
      complexities.

PMID- 22588669
TI  - Hydrogen bonding of excited states in supramolecular host-guest inclusion
      complexes.
AB  - Host-guest inclusion complexes represent an important type of supramolecular
      structure, one which finds widespread applications in diverse areas including
      separations science, the food industry, molecular sensors and optical devices.
      There are several driving forces for the formation of such inclusion complexes in
      solution; one of the most important is hydrogen bonding between the guest and
      host molecules. The nature or strength of the hydrogen bonding may change upon
      electronic excitation of the guest, for example during fluorescence studies or
      when the inclusion complex is used as an optical sensor. In this Perspective
      article, the impact of hydrogen bonding between excited state guests and their
      hosts is examined in detail, in terms of the impact on the formation and
      stability of such excited state complexes, the effects on guest fluorescence,
      changes in the stability of ground state guest complexes upon electronic
      excitation, the application of inclusion complexes as fluorescent sensors and
      materials, and the use of fluorescence spectroscopy for their study.

PMID- 22588670
TI  - Secular changes in personality: study on 75-year-olds examined in 1976-1977 and
      2005-2006.
AB  - OBJECTIVE: In order to study secular changes in personality factors neuroticism
      and extroversion, representative population samples of non-demented 75-year-olds
      underwent psychiatric examinations in 1976-1977 (total n = 223, 138 women, 85
      men) and 2005-2006 (total n = 556, 322 women and 234 men). METHODS: Eysenck
      Personality Inventory was used at both occasions. Demographic factors
      (educational level, marital status, having children) were registered. RESULTS:
      Seventy-five-year-olds examined in 2005-2006 had higher values on extroversion
      and lower values on the Lie scale compared with those examined in 1976-1977.
      Neuroticism did not differ between the two birth cohorts. Neuroticism scores were
      higher in women than in men both in 1976-1977 and 2005-2006, and Lie score was
      higher in women than in men in 2005-2006. CONCLUSIONS: Our findings suggest that
      present cohorts of 75-year-olds are more extroverted and less prone to respond in
      a socially desirable manner than those born three decades earlier. Neuroticism
      levels remained unchanged, suggesting this trait may be less influenced by
      environmental factors than the other traits studied.

PMID- 22588671
TI  - Adipose-derived stem cells on the healing of ischemic colitis: a therapeutic
      effect by angiogenesis.
AB  - BACKGROUND: There has been no specific treatment for ischemic colitis. We
      verified the effects of adipose-derived stem cells (ASCs) on ischemia-induced
      colitis in a rat model. METHODS: Forty male Sprague-Dawley rats (10 weeks old;
      weight, 350 +/- 20 g) were divided into two groups: a control group (only
      fibrinogen and thrombin injected, n = 20) and an ASC group (local implantation of
      ASCs mixed with thrombin and fibrinogen, n = 20). An ischemic colitis model was
      established by modifying Nagahata's methods with double-blind randomization. ASCs
      (1 * 10(6) cells) were implanted intramurally into the ischemic area using a
      fibrin glue mixture. The severity of adhesion, degree of ileus, the number and
      size of the ulcers, Wallace macroscopic and microscopic scores, and microvascular
      density were measured. RESULTS: The degree of ileus was significantly lower, and
      significantly fewer and smaller ulcerations were found in the ASC group than
      those in the control group. Wallace macroscopic and microscopic scores were lower
      in the ASC group than in the control group (1.90 +/- 1.22 versus 3.25 +/- 1.83, p
      < 0.01 and 1.55 +/- 1.88 versus 2.84 +/- 1.89, p < 0.05, respectively).
      Microvascular density was higher in the ASC group than in the control (54.45 +/-
      19.45 versus 26.54 +/- 13.14, p < 0.01, respectively). CONCLUSIONS: Local
      implantation of ASCs into an ischemic-injured colonic wall reduced the grade of
      ischemic injury and enhanced tissue healing by promoting angiogenesis.

PMID- 22588672
TI  - Weight change associated with anastrozole and tamoxifen treatment in
      postmenopausal women with or at high risk of developing breast cancer.
AB  - Weight gain is commonly reported by breast cancer patients on tamoxifen or
      aromatase inhibitors. Since weight gain may impact on outcome and compliance we
      have prospectively assessed the effects of these agents on weight change in three
      randomised trials for the treatment or prevention of breast cancer. Data on
      weight change in postmenopausal women from three large clinical trials
      investigating endocrine therapy for the treatment or prevention of breast cancer
      were analysed (ATAC, IBIS-I and IBIS-II). In the IBIS-I study, mean weight change
      on tamoxifen was +0.1 kg (SD 0.1) compared with +0.3 kg (SD 0.1) in women taking
      the placebo (P = 0.3) between baseline and 12 months of follow-up. In the IBIS-II
      trial, no statistically significant difference was found between anastrozole and
      placebo after 12 months of follow-up [+0.8 kg (SD 5.3) vs. +0.5 kg (SD 7.4), P =
      0.5]. In the ATAC trial, no statistically significant differences in weight gain
      between anastrozole and tamoxifen were found after 12 months of follow-up [+1.4
      kg (SD 3.9) vs. +1.5 kg (SD 4.0), P = 0.4]. Significant baseline predictors for
      gaining more than 5 kg of weight after 12 months of follow-up were: being younger
      than 60 years old, smoking and mastectomy. All three trials demonstrate that
      weight gain occurs primarily within the first 12 months of active treatment in a
      subset of patients. In the prevention trials, weight gain does not differ between
      anastrozole, tamoxifen and placebo and also did not differ between anastrozole
      and tamoxifen in the treatment trial.

PMID- 22588673
TI  - Early breast cancer with positive margins: excellent local control with an
      upfront brachytherapy boost.
AB  - Standard breast conservation therapy consists of lumpectomy and whole breast
      radiation with boost. The effectiveness of radiation in cases of positive margins
      is controversial. Two potential treatment-related factors are time to initiation
      of radiation and localization of the boost. Here, we examine long-term outcomes
      of positive margin cases treated with an upfront interstitial brachytherapy
      boost. This particular treatment arrangement may reduce those treatment-related
      effects on local control. Historically, a low dose interstitial implant was a
      common boost technique. One approach administered the boost before external beam.
      A review of 521 cases treated at our institution was conducted. Patients were
      selected for this study if they received an upfront brachytherapy boost and had
      close or positive margins. Forty-four breast cancers were identified. Median
      follow-up of survivors was 11.3 years (8.1-21.7). Implant was performed at
      lumpectomy (12) or axillary dissection (32). Margin statuses were: focal
      carcinoma at ink (37), multifocal carcinoma at ink (1), carcinoma <1 mm from ink
      (2), and DCIS at ink (4). Median tumor size was 1.2 cm (0.5-3.5 cm). Ten patients
      had nodal involvement. Total median dose was 60 Gy (58.6-65.3 Gy). Median boost
      dose was 15 Gy (12-20.3 Gy). Lumpectomy to boost interval was median of 3 weeks
      (0-10.8). No ipsilateral breast recurrences or second primaries were identified.
      Four developed contralateral breast cancer. Eleven are deceased, four from breast
      cancer-all from metastasis. 12-year Kaplan-Meier estimates were: overall survival
      78 +/- 7 %, cause specific survival 93 +/- 4 %, and recurrence-free survival 82
      +/- 6 %. Univariate analysis identified nodal disease as significant for cause
      specific survival (log rank p = 0.005). No ipsilateral breast recurrences were
      found. Early administered radiation and accurate boost localization were
      identified as suspected treatment-related factors for local recurrence. When
      these two treatment-related factors are minimized, long-term local control rates
      do not suffer.

PMID- 22588675
TI  - Continuous-flow synthesis of activated vitamin D3 and its analogues.
AB  - An efficient, two-stage, continuous-flow synthesis of 1alpha,25-(OH)(2)-vitamin
      D(3) (activated vitamin D(3)) and its analogues was achieved. The developed
      method afforded the desired products in satisfactory yields using a high
      intensity and economical light source, i.e., a high-pressure mercury lamp. In
      addition, our method required neither intermediate purification nor high-dilution
      conditions.

PMID- 22588674
TI  - Urine biomarkers in juvenile-onset SLE nephritis.
AB  - Over 80 % of patients with juvenile-onset systemic lupus erythematosus will have
      renal involvement compared to 40 % with adult-onset disease. Up to 44 % of
      children who do have lupus nephritis (LN) progress to renal failure in early
      adulthood. Improved methods of detecting onset of LN would allow earlier
      treatment, which may prevent irreversible renal scarring and a decline in renal
      function. Current conventional markers of disease activity fail to adequately
      predict renal lupus flares and include proteinuria, complement levels, anti
      double-stranded DNA antibodies and serum creatinine concentrations. Standardized
      histological classification is currently the gold standard for diagnosing and
      classifying LN, but its invasive nature limits routine use for monitoring,
      especially in a childhood population. Novel biomarkers need to be sensitive and
      specific-and preferably non-invasive and cost-effective. The most promising
      biomarkers in juvenile-onset LN include urinary neutrophil gelatinase associated
      lipocalin, monocyte chemoattractant protein 1 and transforming growth factor
      beta, although many others have been identified and are under investigation. No
      one biomarker yet discovered is unique to LN, indicating an overlap in disease
      pathophysiology. It is likely that a combination of biomarkers will be required
      for assessing disease flare detection, response to treatment and prognostic
      information. Potential biomarkers require longitudinal validation in large
      paediatric, prospective cohorts to assess their ability to act as clinically
      useful adjuncts.

PMID- 22588676
TI  - Improvement of physicochemical properties of an antiepileptic drug by salt
      engineering.
AB  - The focus of the present investigation was to evaluate the feasibility of using
      cyclamic salt of lamotrigine in order to improve its solubility and intrinsic
      dissolution rate (IDR). The salt was prepared by solution crystallization method
      and characterized chemically by fourier transform infrared spectroscopy (FTIR),
      proton ((1)H) and carbon ((13)C) nuclear magnetic resonance (liquid and solid,
      NMR) spectroscopy, physically by powder X-ray diffraction (PXRD), thermally by
      differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA),
      physicochemically for solubility, IDR, solution and solid-state stability, and
      polymorphism by solution recrystallization and slurry conversion studies. The
      FTIR, NMR, PXRD, DSC, and TGA spectra and thermograms indicated the salt
      formation. The salt formation increased lamotrigine solubility by 19-fold and IDR
      by 4.9-fold in water. The solution and solid-state stability were similar to
      parent molecule and were resistant to polymorphic transformation. In conclusion,
      cyclamic salt of lamotrigine provides another potential avenue for the
      pharmaceutical development of lamotrigine with improved physicochemical
      properties especially for pediatric population. It is also possible that
      appropriate dosage forms can be formulated with much lower drug amount and better
      safety profile than existing products.

PMID- 22588677
TI  - Gaming, texting, learning? Teaching engineering ethics through students' lived
      experiences with technology.
AB  - This paper examines how young peoples' lived experiences with personal
      technologies can be used to teach engineering ethics in a way which facilitates
      greater engagement with the subject. Engineering ethics can be challenging to
      teach: as a form of practical ethics, it is framed around future workplace
      experience in a professional setting which students are assumed to have no prior
      experience of. Yet the current generations of engineering students, who have been
      described as 'digital natives', do however have immersive personal experience
      with digital technologies; and experiential learning theory describes how
      students learn ethics more successfully when they can draw on personal experience
      which give context and meaning to abstract theories. This paper reviews current
      teaching practices in engineering ethics; and examines young people's engagement
      with technologies including cell phones, social networking sites, digital music
      and computer games to identify social and ethical elements of these practices
      which have relevance for the engineering ethics curricula. From this analysis
      three case studies are developed to illustrate how facets of the use of these
      technologies can be drawn on to teach topics including group work and
      communication; risk and safety; and engineering as social experimentation. Means
      for bridging personal experience and professional ethics when teaching these
      cases are discussed. The paper contributes to research and curriculum development
      in engineering ethics education, and to wider education research about methods of
      teaching 'the net generation'. 

PMID- 22588678
TI  - [Malaria - what's new?].

PMID- 22588679
TI  - Cervical cancer survivors at increased risk of subsequent tobacco-related
      malignancies, United States 1992-2008.
AB  - PURPOSE: Persistent smoking among cancer survivors may increase their risk of
      subsequent malignancies, including tobacco-related malignancies. Despite these
      risks, nearly 40 % of women diagnosed with cervical cancer continue to smoke
      after diagnosis. This study describes the relative risk of developing any
      subsequent and tobacco-related malignancy among cervical cancer survivors.
      METHODS: We examined data from the year 1992 to 2008 in 13 Surveillance,
      Epidemiology and End Results registries. We calculated the standardized incidence
      ratio (SIR) and 95 % confidence limits (CLs) for all subsequent and tobacco
      related malignancies among cervical cancer survivors. Tobacco-related
      malignancies were defined according to the 2004 Surgeon General's Report on the
      Health Consequences of Smoking. For comparison with cervical cancer survivors,
      SIRs for subsequent malignancies were also calculated for female survivors of
      breast or colorectal cancers. RESULTS: The SIR of developing a subsequent tobacco
      related malignancy was higher among cervical cancer survivors (SIR = 2.2, 95 % CL
      = 2.0-2.4). Female breast (SIR = 1.1, 95 % CL = 1.0-1.1) and colorectal cancer
      survivors (1.1, 1.1-1.2) also had an elevated risk. The increased risk of a
      subsequent tobacco-related malignancy among cervical cancer survivors was
      greatest in the first 5 years after the initial diagnosis and decreased as time
      since diagnosis elapsed. CONCLUSION: Women with cervical cancer have a two-fold
      increased risk of subsequent tobacco-related malignancies, compared with breast
      and colorectal cancer survivors. In an effort to decrease their risk of
      subsequent tobacco-related malignancies, cancer survivors should be targeted for
      tobacco prevention and cessation services. Special attention should be given to
      cervical cancer survivors whose risk is almost twice that of breast or colorectal
      cancer survivors.

PMID- 22588680
TI  - Association between habitual dietary flavonoid and lignan intake and colorectal
      cancer in a Spanish case-control study (the Bellvitge Colorectal Cancer Study).
AB  - BACKGROUND: Flavonoid-rich foods, such as fruits, vegetables, and tea, may have a
      protective effect upon colorectal cancer. However, current epidemiological
      evidence for a protective effect of flavonoid intake upon colorectal cancer is
      promising but not conclusive. OBJECTIVE: To examine the relation between dietary
      flavonoid and lignan intakes and the risk of colorectal cancer within a Spanish
      population. DESIGN: Data from the Bellvitge Colorectal Cancer Study, a case
      control study (424 cases with incident colorectal cancer and 401 hospital-based
      controls), were used. A reproducible and validated food frequency questionnaire
      was administered in personal interviews. An ad hoc food composition database on
      flavonoids and lignans was compiled, mainly using data from the US Department of
      Agriculture and Phenol-Explorer databases. Adjusted odds ratios (ORs) and 95 %
      confidence intervals (CIs) were estimated using unconditional logistic regression
      models. RESULTS: An inverse association was found between intake of total
      flavonoids (OR, 0.59; 95 % CI, 0.35-0.99 for the highest vs. the lowest quartile;
      p for trend = 0.04), lignans (OR, 0.59; 95 % CI, 0.34-0.99; p for trend = 0.03),
      and some individual flavonoid subgroups (flavones, proanthocyanidins) and the
      risk of colorectal cancer. Separate analyses by cancer site showed similar
      results. CONCLUSIONS: Intake of total dietary flavonoids (particularly certain
      flavonoid subgroups) and lignans was inversely associated with colorectal cancer
      risk in a Spanish population.

PMID- 22588681
TI  - "A Fire in the Blood": metaphors of bipolar disorder in Jamison's An Unquiet
      Mind.
AB  - Content analysis of three chapters of Jamison's memoir, An Unquiet Mind, shows
      that depression, mania, and Bipolar Disorder have a common metaphoric core as a
      sequential process of suffering and adversity that is a form of malevolence and
      destruction. Depression was down and in, while mania was up, in and distant,
      circular and zigzag, a powerful force of quickness and motion, fieriness,
      strangeness, seduction, expansive extravagance, and acuity. Bipolar Disorder is
      down and away and a sequential and cyclical process that partakes of the
      metaphors of its component moods. We conclude that metaphors of mood disorders
      share a number of structural features and are consistent across different
      authors.

PMID- 22588682
TI  - 'Murder by milligrams': enhancement technologies and therapeutic zeal in Timothy
      Findley's Headhunter".
AB  - In his 1993 novel Headhunter, Canadian author Timothy Findley describes the
      tendency of some medical practitioners to put scientific interests above the
      therapeutic needs of the individual. As the book's title and name of the main
      character Dr. Kurtz attest, Findley reflects the colonialist teleology found in
      Heart of Darkness as an analogue for the therapeutic zeal shown by many of the
      physicians in Headhunter. In the novel, such zeal is especially problematic when
      it is combined with so-called enhancement technologies, since enhancement, like
      colonialism, can be based in the prejudices of the practitioner and/or the
      dominant society, rather than in the needs of the patient. To counter therapeutic
      zeal, Findley, like Conrad, proposes an ethics of restraint in which the
      practitioner's empathy outweighs his or her desire for scientific discovery.

PMID- 22588683
TI  - Effect of irradiation with red and infrared laser in the treatment of oral
      mucositis: a pilot study with patients undergoing chemotherapy with 5-FU.

PMID- 22588684
TI  - Influence of different power outputs of intraoral Nd:YAG laser on shear bond
      strength of a resin cement to nickel-chromium dental alloy.
AB  - Up to now, there is no any experience about the application of dental lasers to
      bond resin composites to metal surfaces in dentistry. The aim of this preliminary
      study was to evaluate if the laser irradiation of ceramic-covered alloy surface
      would improve the bond strength of resin to metal, and if different parameters of
      laser output may influence the strength of this bond. Fifty three cylinders
      (thickness of 5 mm and diameter of 10 mm) were made up of a commercially
      available nickel-chromium alloy by lost-wax technique. Forty prepared specimens
      were divided into four groups. Five specimens in each group were covered by
      slurry of dental opaque porcelain and irradiated by Nd:YAG laser using different
      output parameters for each group. Other five specimens in each group were treated
      using the same laser parameters without porcelain covering. Five sandblasted
      specimen served as control group. Panavia F2.0 was bonded on the metal surfaces
      using polyethylene tubes. In ceramic-coated specimens, silane was applied to
      achieve chemical bond between silica particles and resin cement. All specimens
      were thermocycled and subjected to shear bond strength (SBS) test (50 kgf at 0.5
      mm/min). Two specimens of each ceramic-coated laser-treated groups were studied
      using scanning electron microscopy and wavelength dispersive X-ray spectroscopy
      which showed stabilization of silica particles on the metal surface. ANOVA
      procedure showed that although shear bond strength was significantly higher in
      porcelain-covered laser treated samples, but the effect of power output of laser
      irradiation was not significant (P = 0.917). There were no statistically
      significant difference between SBS in control samples and laser treated specimens
      without porcelain covering. It can be concluded that Nd:YAG laser surface
      treatment may improve the silica coating of alloy surface to achieve better resin
      metal bond.

PMID- 22588685
TI  - Oncological and functional outcome after transoral 532-nm pulsed potassium
      titanyl-phosphate laser surgery for T1a glottic carcinoma.
AB  - The major concerns related to transoral laser surgery (TLS) for T1a glottic
      carcinoma are disease control and postoperative voice. This study examines the
      efficacy of the excision and ablation strategy of TLS using the 532-nm pulsed
      potassium-titanyl-phosphate (KTP) laser as an alternative to the conventional
      carbon dioxide (CO2) laser in treating T1a glottis carcinoma. The tumor was
      excised using KTP laser, followed by circumferential ablation of the mucosa
      surrounding the surgical margin in a non-contact manner using the KTP laser.
      Local control was obtained in 22 of 24 patients (91.7 %). Mean scores on Voice
      Related Quality of Life questionnaire (V-RQOL) and the Voice Handicap Index-10
      (VHI-10) were 81.0 and 6.2, respectively. A highly significant correlation was
      observed between scores of V-RQOL and adjusted VHI-10 (r = 0.96). TLS with a KTP
      laser for early glottic carcinoma achieved acceptable local control and
      postoperative voice comparable to those with a CO2 laser reported in the
      literature, suggesting that the procedure based on an excision and ablation
      strategy can be considered oncologically and functionally acceptable for this
      lesion.

PMID- 22588686
TI  - New approach to the preparation of bicyclo octane derivatives via the
      enantioselective cascade reaction catalyzed by chiral diamine-Ni(OAc)2 complex.
AB  - A highly efficient catalyst system assembled from enantiomerically pure
      diaminocyclohexane and Ni(OAc)(2) is, for the first time, used to catalyze the
      cascade Michael-Henry reaction of various diones and substituted nitroalkenes. A
      series of polyfunctionalized bicyclo[3.2.1]octane derivatives containing four
      stereogenic centers are prepared with excellent enantioselectivities (up to >99%
      ee) and diastereoselectivities (up to 50 : 1 dr) with high yields. In addition,
      via this chiral diamine-Ni(OAc)(2) catalyst system, the base-induced
      epimerization leading to the decrease of stereoselectivity can be prevented.

PMID- 22588687
TI  - Depression subtypes and 5-year risk of dementia and Alzheimer disease in patients
      aged 70 years.
AB  - OBJECTIVE: The objective of this study was to estimate several subtypes of
      depressive disorders as risk factors for dementia and Alzheimer disease (AD)
      specifically. METHODS: This is a population-based cohort study using a sample of
      451 non-demented older people. Adjusted Cox proportional hazard models were
      calculated to determine the association of depression with dementia or AD
      development after 5 years. Baseline evaluation included the Cambridge Mental
      Disorders of the Elderly Examination (CAMDEX). Depressive disorders (major
      episode [MD] and minor depressive disorders [MDDIS]) were assessed following DSM
      IV criteria and further classified according to the age at onset (early versus
      late onset). In turn, all late-onset depressions were grouped as with or without
      depression-executive dysfunction syndrome (DEDS). Dementia (and dementia
      subtypes) diagnoses were made using the CAMDEX. When the patients were deceased,
      the Retrospective Collateral Dementia Interview was used. RESULTS: Late-onset
      depressions (both MD and MDDIS) were associated with increased dementia (hazard
      ratio [HR] = 2.635; 95% CI = 1.153-6.023; and HR = 2.517; 95% CI = 1.200-5.280,
      respectively), and AD (HR = 6.262; 95% CI = 2.017-19.446; and HR = 4.208; 95% CI
      = 1.828-9.685, respectively) after adjustment by age, gender, marital status,
      education, cognitive impairment, executive function and stroke history. A second
      model revealed that only late-onset depressions with DEDS increased the risk for
      both dementia (late-onset MD with DEDS: HR = 6.262; 95% CI = 2.017-19.446; late
      onset MDDIS with DEDS: HR = 4.208; 95% CI = 1.828-9.685) and AD (late-onset MD
      with DEDS: HR = 7.807; 95% CI = 1.567-38.894; late-onset MDDIS with DEDS: HR =
      6.099; 95% CI = 2.123-17.524). CONCLUSIONS: Late-onset depressive episodes with
      DEDS are risk factors for dementia and AD development, regardless of the severity
      of the depression.

PMID- 22588688
TI  - Real-time quantitative monitoring of specific peptide cleavage by a proteinase
      for cancer diagnosis.

PMID- 22588689
TI  - Combining different rotational alignment axes with navigation may reduce the need
      for lateral retinacular release in total knee arthroplasty.
AB  - PURPOSE: The aim of the study was to compare femoropatellar alignment and the
      incidence of lateral retinacular release (LRR) in total knee arthroplasty (TKA)
      in which the rotational alignment of the femoral component was determined using a
      combination of different rotational alignment axes and navigation or a single
      reference axis in the standard procedure. METHODS: We assessed 66 patients
      undergoing TKA in whom the rotation of the femoral component was determined on
      the posterior condylar axis in standard procedures (group A) and 65 patients in
      whom it was determined by combining the posterior condylar axis, anteroposterior
      axis and epicondylar axis in navigated procedures (group B). The mean age was 68
      and 69 years in groups A and B, respectively. Patellar tracking was assessed
      after deflation of the tourniquet and LRR performed in the presence of
      maltracking. Visual analogue scale (VAS), Knee Society Score (KSS), Lonner
      patellar score and patellar tilt were recorded. RESULTS: LRR was carried out in
      18 cases (27 %) in group A and in four (6 %) in group B (p = 0.003). The KSS and
      VAS were improved significantly compared to the preoperative status, but with no
      significant differences between the two groups. The patellar score showed a
      greater improvement in the navigated compared to the standard group at the four
      week follow-up. Patella tilt improved significantly in both groups. The
      complication rate was similar in the two groups. CONCLUSIONS: Combining different
      rotational alignment axes with navigation significantly reduces patellar
      maltracking and the need for LRR compared to the standard procedure in which the
      posterior condylar axis is used as single anatomical reference.

PMID- 22588691
TI  - Establishing the radiation risk from fluoroscopic-assisted arthroscopic surgery
      of the hip.
AB  - PURPOSE: The purpose of the study was to quantify patient exposure to ionising
      radiation during fluoroscopic-assisted arthroscopic surgery of the hip, establish
      a risk profile of this exposure, and reassure patients of radiation safety during
      the procedure. METHODS: We retrospectively analysed the dose area products for 50
      consecutive patients undergoing arthroscopic hip surgery by an experienced hip
      arthroscopic surgeon. The effective dose and organ dose were derived using a
      Monte Carlo program. RESULTS: The mean total fluoroscopy time was 1.10 minutes
      and the mean dose area product value was 297.2 cGycm(2). We calculated the
      entrance skin dose to be 52 mGy to the area where the beam was targeted (81
      cm(2)). The mean effective dose for intra-operative fluoroscopy was 0.33 mSv,
      with a SD of 0.90 Sv. CONCLUSION: This study confirms that fluoroscopic-assisted
      arthroscopic surgery of the hip is safe with a low maximum radiation dose and
      supports its continued use in preference to alternative imaging modalities.

PMID- 22588690
TI  - Interleukin-1 beta influences on lysyl oxidases and matrix metalloproteinases
      profile of injured anterior cruciate ligament and medial collateral ligament
      fibroblasts.
AB  - PURPOSE: The anterior cruciate ligament (ACL) is known to have a poor healing
      ability, especially in comparison with the medial collateral ligament (MCL) which
      can heal relatively well. Interleukin-1beta (IL-1beta) is considered to be an
      important chemical mediator in the acute inflammatory phase of ligament injury.
      The role of IL-1beta-induced expressions of lysyl oxidases (LOXs) and matrix
      metalloproteinases (MMPs), which respectively facilitate extracellular matrix
      (ECM) repair and degradation, is poorly understood. In this study, we aim to
      determine the intrinsic differences between ACL and MCL by characterising the
      differential expressions of LOXs and MMPs in response to IL-1beta in the injury
      process. METHODS: Semi-quantitative polymerase chain reaction (PCR), quantitative
      real-time PCR, Western blot, and zymography were performed. RESULTS: We detected
      high expressions of IL-1beta-induced LOXs in normal ACL and MCL. Then, we found
      IL-1beta induced injured MCL to express more LOXs than injured ACL (up to 2.85
      fold in LOX, 2.58-fold in LOXL-1, 1.89-fold in LOXL-2, 2.46-fold in LOXL-3 and
      2.18-fold in LOXL-4). Meanwhile, we found IL-1beta induced injured ACL to express
      more MMPs than injured MCL (up to 1.72-fold in MMP-1, 1.95-fold in MMP-2, 2.05
      fold in MMP-3 and 2.3-fold in MMP-12). The further protein results coincided with
      gene expressions above. CONCLUSIONS: Lower expressions of LOXs and higher
      expressions of MMPs might help to explain the poor healing ability of ACL.

PMID- 22588692
TI  - The effect of epineurotomy on the median nerve volume after the carpal tunnel
      release: a prospective randomised double-blind controlled trial.
AB  - PURPOSE: The purpose of this study was to evaluate the effects of epineurotomy on
      the post-surgical median nerve volume and clinical outcomes in carpal tunnel
      syndrome (CTS) patients with a prominent nerve narrowing. METHODS: This was a
      prospective, randomised, double-blind controlled trial. Patients (n = 50) were
      randomised (1:1) to open-field surgical carpal tunnel release followed by a
      longitudinal epineurotomy of the nerve (test), or to open-field release without
      epineurotomy (control). RESULTS: The nerve volume was slightly larger in the test
      group 90 days post-surgery (by 10.5 %, p = 0.157) but not 180 days post-surgery.
      No relevant electropyhsiological or clinical difference between groups and no
      effect of the nerve volume was observed. The subjective pain reduction was
      slightly more prominent in the control group at 180 days. Larger post-surgical
      nerve volume was associated with lower pain, but only in the control group.
      CONCLUSIONS: Even in selected CTS patients, longitudinal epineurotomy confers no
      benefit regarding the nerve volume or clinical outcomes over a simple carpal
      tunnel release.

PMID- 22588694
TI  - Chevron-type medial malleolar osteotomy: a functional, radiographic and
      quantitative T2-mapping MRI analysis.
AB  - PURPOSE: The purpose of this study was to retrospectively evaluate a large series
      of patients for functional, radiographic and MRI outcomes after a Chevron-type
      medial malleolar osteotomy. METHODS: Sixty-two patients underwent a Chevron-type
      medial malleolar osteotomy with a median follow-up of 34.5 months. Standard
      digital radiographs were used to determine bony union and the angle of the
      osteotomy relative to the longitudinal axis of the tibia. Morphologic and
      quantitative T2-mapping MRI was also analysed in 32 patients. RESULTS: Fifty
      eight patients (94 %) reported being asymptomatic at the site of the medial
      malleolar osteotomy. The median time to healing on standard radiograph was 6
      weeks (range, 4-6 weeks) with an angle of 31.7 degrees  +/- 6.9 degrees .
      Quantitative T2-mapping MRI analysis demonstrated that the deep half of interface
      repair tissue had relaxation times that were not significantly different from
      normal tibial cartilage. In contrast, interface repair tissue in the superficial
      half demonstrated significant prolongation from normal relaxation time values,
      indicating a more fibrocartilaginous repair. Four patients (6 %) reported pain
      post-operatively. CONCLUSION: A Chevron-type medial malleolar osteotomy
      demonstrates satisfactory healing and fixation, with fibrocartilaginous tissue
      evident superficially at the osteotomy interface. Further investigation is
      warranted in the form of longitudinal study to assess the long-term outcomes of
      medial malleolar osteotomy.

PMID- 22588693
TI  - The cartilage degeneration and joint motion of bipolar hemiarthroplasty.
AB  - PURPOSE: The outcomes of bipolar hemiarthoplasty for osteonecrosis of femoral
      head have been disappointing due to cartilage degeneration and osteolysis. We
      investigated the cartilage degeneration, joint motion, and factors associated
      with osteolysis. METHODS: We retrospectively reviewed 134 bipolar
      hemiarthroplasties. The wear rate of acetabular cartilage was calculated. The
      ranges of motion of outer bearing and inner bearing were determined, and the
      ratio (O/I ratio) was calculated. RESULTS: The mean degeneration rate of
      acetabular cartilage was 0.34 +/- 0.35 mm/year. We could observe that the outer
      bearing motion was dominant, but decreased over time. In addition, the
      degeneration rate of cartilage and the decline rate of outer bearing motion of
      the osteolysis group were significantly higher than those of the control group.
      CONCLUSIONS: Close observation is needed in cases of high degeneration rate of
      cartilage and rapid decline of outer bearing motion due to possibility of
      osteolysis.

PMID- 22588695
TI  - The outcomes after anterior cruciate ligament reconstruction in adolescents with
      open physes.
AB  - PURPOSE: We evaluated the clinical outcome of anterior cruciate ligament
      reconstruction (ACLR) in adolescents with open physes and compared those results
      with adults. MATERIALS AND METHODS: Fifteen adolescents with open physes
      underwent physeal-sparing double-bundle ACLR using hamstring autograft. The
      median age of the adolescents was 14 years (range 13-16 years). Forty adults
      underwent anatomic double-bundle ACLR during the same period of this study. The
      median age of the adults was 26 years (range 17-39 years). Clinical outcomes were
      evaluated in terms of manual Lachman test, pivot shift test and the results of KT
      2000 arthrometer. Additionally, we evaluated clinical outcome in terms of
      International Knee Documentation Committee (IKDC) score and Lysholm Knee Scoring
      Scale. We also evaluated rates of re-rupture. RESULTS: No clinically significant
      growth abnormalities were observed in adolescent cases. In the Lachman test, two
      of the 15 adolescents had a positive, whereas one of the 40 adults had a positive
      (n.s.). In the pivot shift test, three of the 15 adolescents had a positive,
      whereas two of the 40 adults had a positive (n.s.). There was no statistically
      significant difference between adolescents and adults, in the mean side-to-side
      difference in KT-2000 measurements (1.5 +/- 1.5 mm vs. 1.1 +/- 1.9 mm: n.s.), the
      median IKDC score (96.7 vs. 97.3: n.s.) and Lysholm Scale (99 vs. 98: n.s.),
      rates of re-rupture (13.3 vs. 7.5 %: n.s.). CONCLUSION: Physeal-sparing ACLR with
      hamstring autograft in adolescents with open physes resulted in good clinical
      outcomes similar to those of ACLR in adults without growth abnormalities.

PMID- 22588696
TI  - Composition-tunable vertically aligned CdS(x)Se(1-x) nanowire arrays via van der
      Waals epitaxy: investigation of optical properties and photocatalytic behavior.

PMID- 22588697
TI  - Gold(I)-catalysed cycloisomerisation of 1,6-cyclopropene-enes.
AB  - The gold(I)-catalysed cycloisomerisation of appropriately substituted 1,6
      cyclopropene-enes proceeds through regioselective electrophilic ring opening of
      the three-membered ring to generate an alkenyl gold carbenoid that achieves the
      intramolecular cyclopropanation of the remote olefin. This strategy allows
      straightforward, highly efficient and diastereoselective access to a variety of
      substituted 3-oxa- and 3-azabicyclo[4.1.0]heptanes, as well as to
      bicyclo[4.1.0]heptan-3-ol derivatives. Since the isopropylidene group in the
      resulting cycloisomerisation products can be subjected to ozonolysis, 3,3
      dimethylcyclopropenes behave as interesting surrogates for alpha-diazoketones.

PMID- 22588698
TI  - A model approach to project the start of egg laying of Great Tit (Parus major L.)
      in response to climate change.
AB  - The aim of this study was to select a phenological model that is able to
      calculate the beginning of egg laying of Great Tit (Parus major) for both current
      and future climate conditions. Four models (M1-M4) were optimised on long-term
      phenological observations from the Ecological Research Centre Schluchtern
      (Hessen/Germany). Model M1 was a common thermal time model that accumulates
      growing degree days (GDD) on an optimised starting date t (1). Since egg laying
      of Great Tit is influenced not only by air temperature but also by photoperiod,
      model M1 was extended by a daylength term to give M2. The other two models, M3
      and M4, correspond to M1 and M2, but t (1) was intentionally set to 1 January, in
      order to consider already rising temperatures at the beginning of the year. A
      comparison of the four models led to following results: model M1 had a relatively
      high root mean square error at verification (RMSE(ver)) of more than 4 days and
      can be used only to calculate the start of egg laying for current climate
      conditions because of the relatively late starting date for GDD calculation. The
      model failed completely if the starting date was set to 1 January (M3).
      Consideration of a daylength term in models M2 and M4 improved the performance of
      both models strongly (RMSE(ver) of only 3 days or less), increased the
      credibility of parameter estimation, and was a precondition to calculate reliable
      projections in the timing of egg laying in birds for the future. These results
      confirm that the start of egg laying of Great Tit is influenced not only by air
      temperature, but also by photoperiod. Although models M2 and M4 both provide
      comparably good results for current climate conditions, we recommend model M4
      with a starting date of temperature accumulation on 1 January-for calculating
      possible future shifts in the commencement of egg laying. Our regional
      projections in the start of egg laying, based on five regional climate models
      (RCMs: REMO-UBA, ECHAM5-CLM, HadCM3-CLM, WETTREG-0, WETTREG-1, GHG emission
      scenario A1B), indicate that in the near future (2011-2040) no significant change
      will take place. However, in the mid- (2041-2070) and long-term (2071-2100) range
      the beginning of egg laying could be advanced significantly by up to 11 days on
      average of all five RCMs. This result corresponds to the already observed shift
      in the timing of egg laying by about 1 week, due mainly to an abrupt increase in
      air temperature at the end of the 1980s by 1.2 K between April and May. The use
      of five regional climate scenarios additionally allowed to estimate uncertainties
      among the RCMs.

PMID- 22588699
TI  - Validation of an ultrasound-guided technique to establish a liver-to-coelom ratio
      and a comparative analysis of the ratios among acclimated and recently wild
      caught southern stingrays, Dasyatis americana.
AB  - Southern stingrays, Dasyatis americana, are a well-represented elasmobranch
      species in public aquaria and other facilities throughout the world. This study
      was conducted at a facility that experienced some mortality and replenished the
      collection with wild-caught stingrays. A common necropsy finding among the
      stingrays was a small, dark liver. The objectives of this study were to assess
      the reliability of an ultrasound-guided technique for establishing a liver-to
      coelom ratio by calculating the approximate length of the liver with respect to
      the coelomic cavity length and then to compare ratios between acclimated captive
      and wild-caught stingrays. The ultrasound validation phase of the study measured
      the distance from the caudal margin of the liver to the pelvic cartilaginous
      girdle and compared it to the actual distance measured during the necropsy or
      surgery. There was no significant difference found between the ultrasound and
      actual distance measurements (P = 0.945). This technique was then used to
      establish liver-to-coelom ratios and compare two groups of stingrays, presumably
      under different metabolic states at different periods. Liver-to-coelom ratios
      were established during initial examinations as well as 8 months after
      cohabitation in a touch pool exhibit. There were significant differences in liver
      to-coelom ratios between the two stingray groups at introduction (median
      difference = 30.9%, P = 0.007) and after 8 months (median difference = 20.5%, P =
      0.008). There were also significant differences in the liver-to-coelom ratios
      within each group at introduction and at 8 months (acclimated group median
      difference = 20.4%, P = 0.018; wild-caught group median difference 31%, P =
      0.008).

PMID- 22588700
TI  - Genetics of coronary artery disease in the 21st century.
AB  - Coronary artery disease (CAD) is still the number-one killer in the world, and
      clinical trials indicate that it is preventable. Mortality and morbidity can be
      reduced by at least 30% to 40% by treating known risk factors. Genetic
      susceptibility is claimed to account for 50% of predisposition. The challenge of
      preventing CAD in this century, as claimed by some investigators, will require a
      more comprehensive prevention and treatment of environmental and genetic risk
      factors. Part of that challenge has been met by genome-wide association studies,
      which have identified 36 genetic variants with increased risk for CAD. All of
      these genetic variants have reached genome-wide significance (5 * 10(-8) ) and
      replicate in independent populations with large sample sizes. More than 50% of
      these variants occur in >50% of the population, with 10 occurring in >75% of the
      population. The challenge and the opportunity lie in the observation that >66% of
      these risk variants do not mediate their risk through known conventional risk
      factors. These results suggest that genetic predisposition for CAD is conferred
      by common DNA variants and many factors contributing to the pathogenesis of CAD
      are yet to be determined. Comprehensive prevention of CAD will most likely
      require combating genetic and environmental risk factors. We are on the cusp of
      genetic screening, and new therapeutic targets are becoming available to manage
      both genetic and environmental risk factors for CAD.

PMID- 22588701
TI  - Introduction to the themed issue dedicated to Kurt Schaffner.

PMID- 22588702
TI  - Representation of developing countries in orthopaedic journals: a survey of four
      influential orthopaedic journals.
AB  - BACKGROUND: The developing world contains more than 3/4 of the world's
      population, and has the largest burden of musculoskeletal disease. Published
      studies provide crucial information that can influence healthcare policies.
      Presumably much information regarding burden in the developing world would arise
      from authors from developing countries. However, the extent of participation of
      authors from the developing world in widely read orthopaedic journals is unclear.
      PURPOSE: We surveyed four influential English-language orthopaedic journals to
      document the contributions of authors from developing countries. METHODS: We
      surveyed Clinical Orthopaedics and Related Research, Journal of Orthopaedic
      Trauma, and the American and British volumes of The Journal of Bone and Joint
      Surgery, from May 2007 through May 2010. The country of origin of all authors was
      identified. We used the designations provided by the International Monetary Fund
      to define countries as either developed or developing. RESULTS: Two hundred sixty
      five of 3964 publications (7%) included authors from developing countries. Ninety
      percent of these had authors from developing countries with industrialized and
      emerging-market economies. Publications from Sub-Saharan Africa accounted for
      only 0.4% of the 3964 articles reviewed and 5.6% of the 265 articles with
      developing world authorship. Countries with the least robust economies were least
      represented. Less than 1/3 of articles with authors from the developing world had
      coauthors from developed or other developing countries. CONCLUSION: Additional
      studies are needed to determine the reasons for the low representation noted and
      to establish strategies to increase the number of orthopaedic publications from
      parts of the world where the burden of musculoskeletal disease is the greatest.

PMID- 22588703
TI  - Modeling the relationship between Higuchi's fractal dimension and Fourier spectra
      of physiological signals.
AB  - The exact mathematical relationship between FFT spectrum and fractal dimension
      (FD) of an experimentally recorded signal is not known. In this work, we tried to
      calculate signal FD directly from its Fourier amplitudes. First, dependence of
      Higuchi's FD of mathematical sinusoids on their individual frequencies was
      modeled with a two-parameter exponential function. Next, FD of a finite sum of
      sinusoids was found to be a weighted average of their FDs, weighting factors
      being their Fourier amplitudes raised to a fractal degree. Exponent dependence on
      frequency was modeled with exponential, power and logarithmic functions. A set of
      280 EEG signals and Weierstrass functions were analyzed. Cross-validation was
      done within EEG signals and between them and Weierstrass functions. Exponential
      dependence of fractal exponents on frequency was found to be the most accurate.
      In this work, signal FD was for the first time expressed as a fractal weighted
      average of FD values of its Fourier components, also allowing researchers to
      perform direct estimation of signal fractal dimension from its FFT spectrum.

PMID- 22588704
TI  - Identification of leukemia stem cells in acute myeloid leukemia and their
      clinical relevance.
AB  - Acute myeloid leukemia (AML) is considered to be a disease of stem cells. A rare
      defective stem cell population is purported to drive tumor growth. Similarly to
      their normal counterparts, leukemic stem cells (LSC) divide extreme slowly. This
      may explain the ineffectiveness of conventional chemotherapy in combatting this
      disease. Novel treatment strategies aimed at disrupting the binding of LSC to
      stem cell niches within the bone marrow might render the LSC vulnerable to
      chemotherapy and thus improving treatment outcome. This review focuses on the
      detection of LSC, our current knowledge about their cellular and molecular
      biology, and LSC interaction with the niche. Finally, we discuss the clinical
      relevance of LSC and prospective targeted treatment strategies for patients with
      AML.

PMID- 22588705
TI  - The diagnosis of depression and use of antidepressants in nursing home residents
      with and without dementia.
AB  - OBJECTIVE: To compare the prevalence of diagnosed depressive disorders,
      depressive symptoms and use of antidepressant medication between nursing home
      residents with and without dementia. METHODS: This cross-sectional study used
      Minimal Data Set of the Resident Assessment Instrument 2.1 data collected in
      seven nursing homes located in an urbanized region in the Netherlands. Trained
      nurse assistants recorded all medical diagnoses made by a medical specialist,
      including dementia and depressive disorder, and medication use. Depressive
      symptoms were measured with the Depression Rating Scale. Multivariate logistic
      regression analysis was used to compare data between residents with and without
      dementia. RESULTS: Included in the study were 1885 nursing home residents (aged
      65 years or older), of which 837 had dementia. There was no significant
      difference in the prevalence of diagnosed depressive disorder between residents
      with (9.6%) and without dementia (9.8%). Residents with dementia (46.4%) had more
      depressive symptoms than residents without dementia (22.6%). Among those with
      depressive symptoms, residents with dementia had the same likelihood of being
      diagnosed with a depressive disorder as residents without dementia. Among
      residents with a diagnosed depressive disorder, antidepressant use did not differ
      significantly between residents with dementia (58.8%) and without dementia
      (57.3%). The same holds true for residents with depressive symptoms, where
      antidepressant use was 25.3% in residents with dementia and 24.6% in residents
      without dementia. CONCLUSIONS: Regarding the prevalence rates of diagnosed
      depressive disorder and antidepressant use found in this study, our findings
      demonstrate that there is room for improvement not only for the detection of
      depression but also with regard to its treatment.

PMID- 22588706
TI  - Denosumab--a powerful RANKL inhibitor to stop lytic metastases and other bone
      loss actions by osteoclasts.
AB  - Denosumab is a perfect example on the targeted anticancer therapy. The inhibition
      of RANKL activity suppressed the osteoclasts' resorptive function and so
      prevented skeletal related events. This effect is useful not only against bone
      metastases, but also in the treatment of other diseases caused by bone loss. In
      different solid tumors with bone metastasis the quality of life also improved,
      although the overall survival usually showed no change. On the market the main
      competitors for denosumab are still the bisphosphonates (questions of costs and
      reimbursement are not discussed) and some potential new agents e.g. Src kinases
      (as dasatinib, saracatinib, bosutinib), cathepsin K inhibitors, (e.g.
      odanacatib), and new selective estrogen receptor modulators (e.g. bazedoxifene,
      lasofoxifene). Nevertheless, today denosumab is one of the most powerful agents
      in bone-saving area.

PMID- 22588707
TI  - Proteinuria in metastatic pheochromocytoma is associated with an increased risk
      of Acute Respiratory Distress Syndrome, spontaneously or after therapy with 131I
      meta-iodobenzylguanidine (131I-MIBG).
AB  - Acute Respiratory Distress Syndrome (ARDS) has been reported rarely in
      pheochromocytoma, occurring spontaneously or after therapy with 131I-meta
      iodobenzylguanidine (131I-MIBG). Our objective was to determine whether
      proteinuria is associated with an increased risk of ARDS. This was a
      retrospective analysis of a prospective cohort study of 64 patients with
      metastatic pheochromocytoma or paraganglioma treated with 131I-MIBG on
      institutional protocols. Proteinuria was defined as at least one urinalysis
      positive for at least trace protein within 1 month prior to 131I-MIBG or within 1
      month prior to spontaneous ARDS. Proportions were compared using Fisher's exact
      test. Urinalyses within the defined time period were available for 48 patients, 8
      of whom had proteinuria. Of the 8 patients with proteinuria, 5 developed ARDS: 3
      within 10 days following 131I-MIBG, two 6 months following 131I-MIBG. Both
      patients who developed ARDS 6 months after 131I-MIBG had proteinuria within 1
      month before apparently spontaneous ARDS. None of the 40 patients whose
      urinalyses were all negative for protein developed ARDS. None of the 16 patients
      with missing urinalyses developed ARDS. Patients with antecedent proteinuria were
      more likely to develop ARDS than those without proteinuria (63% vs. 0%;
      p<0.0001). The following variables were not significantly associated with ARDS:
      131I-MIBG activities administered, number of 131I-MIBG administrations, age,
      hypertension, or secretion of catecholamines or metanephrines. In patients with
      metastatic pheochromocytoma or paraganglioma, proteinuria is associated with ARDS
      and urine protein should be examined prior to administering 131I-MIBG.

PMID- 22588708
TI  - Stimulatory effect of allantoin on imidazoline I1 receptors in animal and cell
      line.
AB  - Allantoin is known as the agonist of imidazoline receptor, especially the I2
      subtype. Effect of allantoin on imidazoline I1 receptor (I1R) relating to
      reduction of blood pressure and its merit in steatosis are still obscure. Also,
      farnesoid X receptor (FXR) plays an important role in lipid homeostasis related
      to I1R activation. Thus, we administered allantoin into high fat diet (HFD)-fed
      mice showing hypertriglyceridemia and hypercholesterolemia. Allantoin
      significantly improved hyperlipidemia in HFD mice after 4 weeks of
      administration. Pretreatment with efaroxan, at a dose sufficient to inhibit I1R
      activation, attenuated the action of allantoin. In addition, in cultured HepG2
      cells, allantoin increased the expression of farnesoid X receptor (FXR). The
      allantoin-induced FXR expression was blocked by efaroxan. Similar changes were
      observed in the expressions of FXR-targeted genes. Otherwise, allantoin also
      lowered systolic blood pressure (SBP) in HFD mice that can be blocked by
      efaroxan. Taken together, allantoin has an ability to activate I1R for
      improvement of metabolic disorders.

PMID- 22588709
TI  - Dynamic mixtures: challenges and opportunities for the amplification and sensing
      of scents.
AB  - Nature generates compounds as complicated mixtures, but surprisingly little is
      known about the synergies or inhibitory effects of compound mixtures, which is
      likely to become an important research area in life sciences in the near future.
      Some recently developed concepts in dynamic combinatorial/covalent chemistry
      (DCC) have been applied to amplify (increase the intensity and long-lastingness
      of perception) and sense (selectively detect and discriminate) individual
      bioactive volatile molecules in compound mixtures. This Concept article focuses
      on the potential of DCC to impact and modulate the biological and chemical
      properties of mixtures of bioactive volatile compounds to gain a more fundamental
      understanding of the properties of compound mixtures in molecular recognition.

PMID- 22588710
TI  - Validation of the Head and Neck Patient Symptom Checklist as a nutrition impact
      symptom assessment tool for head and neck cancer patients.
AB  - PURPOSE: The purpose of this study was to test the validity of the Head and Neck
      Patient Symptom Checklist (HNSC). METHODS: Three hundred and sixty-eight
      treatment-naive individuals with head and neck cancer prospectively completed the
      HNSC and the Patient-Generated Symptom Global Assessment (PG-SGA). The predictive
      validity was determined by comparing the HNSC symptoms interference scores to the
      PG-SGA scores. Multivariate logistic regression was used to determine the HNSC
      symptoms scores associated with reduced dietary intake, >= 5 % weight loss over 6
      months, and reduced functional performance (FP). RESULTS: HNSC sensitivity (79-98
      %), specificity (99-100 %), positive predictive value (92-100 %), and negative
      predictive value (94-100 %) were excellent, and the Cronbach's alpha coefficient
      was 0.92. The multivariate logistic regression showed that advanced tumor stage,
      pain, loss of appetite (LOA), and difficulty swallowing significantly predicted
      dietary intake. Advanced tumor stage, LOA, and difficulty swallowing were also
      significant predictors of >= 5 % weight loss over 6 months. LOA, difficulty
      swallowing, feeling full, and lack of energy were significant predictors of
      reduced FP. CONCLUSIONS: The HNSC appears to be a valid tool for determining
      symptoms interfering with dietary intake of head and neck cancer (HNC) patients.
      This instrument may aid in early identification of symptoms that place HNC
      patients at risk for reductions in dietary intake, weight, and functional
      performance.

PMID- 22588711
TI  - Non-contrast MR imaging for detecting endoleak after abdominal endovascular
      aortic repair.
AB  - Our aim was to investigate the possibility of ruling out endoleak after
      endovascular aortic repair (EVAR) of abdominal aortic aneurysm (AAA) using non
      contrast MRI. Twenty-three patients (20 males, aged 73 +/- 8 years) with an EVAR
      treated AAA underwent 1.5-T MRI using axial, coronal and sagittal oblique true
      FISP sequences. Two blinded and independent readers with 4 (R1) and 2 (R2) years
      of experience evaluated these images considering an area of even less than 5 mm
      in diameter with a signal intensity higher than that of normal muscles visible in
      the excluded aneurysmal sac as a sign of potential endoleak. The final
      assessment, mainly based on MR angiography and previous examinations, served as
      reference standard. Out of 23 patients, 13 (57%) were negative for endoleak at
      final assessment, while the remaining 10 (43%) were positive, with the following
      type distribution: Ia (n = 4), Ib (n = 2), II (n = 3), and III (n = 1).
      Sensitivity was 10/10 (100%; CI 95% 69-100%), specificity 7/13 (54%; 25-81%),
      accuracy 17/23 (74%; 52-90%), PPV 10/16 (63%; 35-85%) and NPV 7/7 (100%; 59-100%)
      for R1; 9/10 (90%; 56-100%), 8/13 (62%; 32-86%), 17/23 (74%; 52-90%), 9/14 (64%;
      35-8%), and 8/9 (89%; 52-100%) for R2, respectively. Inter-reader Cohen kappa was
      0.810. A negative non-contrast true-FISP MR study can be used to rule out
      endoleak after EVAR of AAA. This hypothesis may contribute to the reduction of
      ionizing radiation exposure and contrast material administration for monitoring
      patients with an EVAR-treated AAA.

PMID- 22588712
TI  - Novel computed tomography indexes of left atrial appendage stasis.
AB  - Contrast enhanced multi-detector computed tomography (MDCT) may detect left
      atrial appendage (LAA) thrombus; however, its ability to qualify LAA stasis has
      not been studied. We sought to identify MDCT derived LAA radiographic parameters
      which could qualify LAA stasis as defined by established transesophageal
      echocardiography (TEE) parameters. Pre-procedural MDCT followed by TEE (median
      procedural time difference of 11 days) from 45 patients who underwent ablation
      for atrial fibrillation were analyzed retrospectively. Contrast enhanced, non
      gated, helical MDCT (64 detector row) was performed according to the
      institutional protocol. Using a combination of parametric and nonparametric
      tests, the mean attenuation and heterogeneity parameters of LAA attenuation were
      correlated with the presence of spontaneous echocardiographic contrast and
      Doppler derived LAA emptying velocity on TEE. If significant correlation is
      observed, a receiver operating curve analysis will be performed. The baseline
      characteristics of the studied population were; age, 62 +/- 11; CHADS2 score, 2.0
      +/- 1.2; heart rate, 79 +/- 10 bpm; left ventricular ejection fraction, 49 +/-
      14%. SEC was seen on TEE in 19 patients; ten with mild, eight with moderate, and
      one had severe SEC. No patients had LAA thrombus. Compared with the group without
      SEC, those with SEC had significantly increased coefficient of variation (0.19
      vs. 0.14, p = 0.014) and range to mean ratio (1.04 vs. 0.73, p = 0.011). There
      was no significant correlation between mean LAA attenuation and LAA emptying
      velocity. However, the range, range to mean ratio, standard deviation and
      coefficient of variation of LAA attenuation had a significantly negative
      correlation with LAA emptying velocity (r = -0.486, r = -0.497, r = -0.434, r = 
      0.466, respectively, all p < 0.05). On receiver operating curve analysis, each of
      the heterogeneity parameters significantly discriminated LAA emptying velocities
      <=30 cm/s, with areas under the curve of 0.88, 0.83, 0.81 and 0.76 respectively.
      In patients with atrial fibrillation, increased contrast heterogeneity within the
      LAA on MDCT correlated with decreased LAA emptying velocity on TEE. Contrast
      enhanced MDCT provides an adjunctive, noninvasive technique for Qualification of
      LAA stasis.

PMID- 22588713
TI  - Characterization of right atrial function and dimension in top-level athletes: a
      speckle tracking study.
AB  - Although many echocardiographic studies are available about the adaptation of
      left ventricle to intensive training, right heart function has been poorly
      investigated and no data are available about the right atrial (RA) function in
      top-level athletes. The aim of the study was to investigate RA function and
      dimension by standard echocardiography and 2D speckle tracking echocardiography
      (STE). One hundred top-levels athletes were recruited from professional sports
      team and were compared with 78 normal subjects. Athletes during an off-training
      period or during prolonged forced rest resulting from injuries were excluded. Top
      level athletes had higher BSA as compared with controls and, as expected, a lower
      resting heart rate (p <= 0.001). RA area, volume, and volume index were
      significantly greater in athletes than in controls (p <= 0.001). This increase
      was associated with greater right ventricular and inferior vena cava diameters (p
      <= 0.001). Peak atrial longitudinal strain and peak atrial contraction strain
      values were significantly lower in athletes in comparison with controls (40.92 +/
      9.86% vs. 48.00 +/- 12.68%, p <= 0.001; 13.05 +/- 4.84% vs. 15.99 +/- 5.74%, p
      <= 0.001, respectively). Interestingly, while athletes presented a higher E/A
      ratio (p <= 0.001) and a lower peak A velocity (p <= 0.001), the E/e' ratio did
      not differ between the two groups. In top-level athletes the RA presents a
      physiological adaptation to intensive exercise conditioning which determines not
      only a morphological but also a functional remodeling. We reported for the first
      time reference values of RA strain in elite athletes, demonstrating that 2D STE
      is a useful tool to investigate RA longitudinal myocardial deformation dynamics
      in athlete's heart.

PMID- 22588714
TI  - Towards textile energy storage from cotton T-shirts.
AB  - A simple chemical activation route is developed to convert insulating cotton T
      shirt textiles into highly conductive and flexible activated carbon textiles
      (ACTs) for energy-storage applications. Such conversion gives these ACTs an ideal
      electrical double-layer capacitive behavior. The constructed asymmetric
      supercapacitors based on the ACTs and MnO(2)/ACT composite show superior
      electrochemical performances.

PMID- 22588715
TI  - RNase P branches out from RNP to protein: organelle-triggered diversification?
AB  - RNase P is the enzyme that removes 5' leader sequences from precursor tRNAs.
      Remarkably, in most organisms, RNase P is a ribonucleoprotein particle where the
      RNA component is responsible for catalysis. In this issue of Genes & Development,
      Gutmann and colleagues (pp. 1022-1027) report the first organism, Arabidopsis
      thaliana, to employ protein-only RNase P in both its nucleus and organelles. An
      intriguing possibility is that replacement of RNase P ribonucleoprotein particles
      (RNPs) by proteins may have been triggered by the acquisition of organelles.

PMID- 22588717
TI  - Suprainduction of p53 by disruption of 40S and 60S ribosome biogenesis leads to
      the activation of a novel G2/M checkpoint.
AB  - Impairment of ribosome biogenesis leads to p53 induction and cell cycle arrest, a
      checkpoint involved in human disease. Induction of p53 is attributed to the
      binding and inhibition of human double minute 2 (Hdm2) by a subset of ribosomal
      proteins (RPs): RPS7, RPL5, RPL11, and RPL23. However, we found that only RPL11
      or RPL5, in a mutually dependent manner, elicit this response. We show that
      depletion of RPS7 or RPL23, like depletion of other RPs, except for RPL11 and
      RPL5, induces a p53 response and that the effects of RPS7 and RPL23 on p53
      induction reported earlier may be ascribed to inhibition of global translation.
      Moreover, we made the surprising observation that codepletion of two essential
      RPs, one from each subunit, but not the same subunit, leads to suprainduction of
      p53. This led to the discovery that the previously proposed RPL11-dependent
      mechanism of p53 induction, thought to be caused by abrogation of 40S biogenesis
      and continued 60S biogenesis, is still operating, despite abrogation of 60S
      biogenesis. This response leads to both a G1 block and a novel G2/M block not
      observed when disrupting either subunit alone. Thus, induction of p53 is mediated
      by distinct mechanisms, with the data pointing to an essential role for ribosomal
      subunits beyond translation.

PMID- 22588716
TI  - Orchestrating transcriptional control of adult neurogenesis.
AB  - Stem cells have captured our imagination and generated hope, representing a
      source of replacement cells to treat a host of medical conditions. Tucked away in
      specialized niches, stem cells maintain tissue function and rejuvenate organs.
      Balancing the equation between cellular supply and demand is especially important
      in the adult brain, as neural stem cells (NSCs) in two discrete regions, the
      subgranular zone (SGZ) of the dentate gyrus and the subventricular zone (SVZ)
      next to the lateral ventricles, continuously self-renew and differentiate into
      neurons in a process called adult neurogenesis. Through the interplay of
      intrinsic and extrinsic factors, adult neurogenic niches ensure neuronal turnover
      throughout life, contributing to plasticity and homeostatic processes in the
      brain. This review summarizes recent progress on the molecular control of adult
      neurogenesis in the SGZ and SVZ, focusing on the role of specific transcription
      factors that mediate the progression from NSCs to lineage-committed progenitors
      and, ultimately, the generation of mature neurons and glia.

PMID- 22588718
TI  - Endoplasmic reticulum protein BI-1 regulates Ca2+-mediated bioenergetics to
      promote autophagy.
AB  - Autophagy is a lysosomal degradation pathway that converts macromolecules into
      substrates for energy production during nutrient-scarce conditions such as those
      encountered in tumor microenvironments. Constitutive mitochondrial uptake of
      endoplasmic reticulum (ER) Ca2+ mediated by inositol triphosphate receptors
      (IP3Rs) maintains cellular bioenergetics, thus suppressing autophagy. We show
      that the ER membrane protein Bax inhibitor-1 (BI-1) promotes autophagy in an IP3R
      dependent manner. By reducing steady-state levels of ER Ca2+ via IP3Rs, BI-1
      influences mitochondrial bioenergetics, reducing oxygen consumption, impacting
      cellular ATP levels, and stimulating autophagy. Furthermore, BI-1-deficient mice
      show reduced basal autophagy, and experimentally reducing BI-1 expression impairs
      tumor xenograft growth in vivo. BI-1's ability to promote autophagy could be
      dissociated from its known function as a modulator of IRE1 signaling in the
      context of ER stress. The results reveal BI-1 as a novel autophagy regulator that
      bridges Ca2+ signaling between ER and mitochondria, reducing cellular oxygen
      consumption and contributing to cellular resilience in the face of metabolic
      stress.

PMID- 22588720
TI  - The Stat6-regulated KRAB domain zinc finger protein Zfp157 regulates the balance
      of lineages in mammary glands and compensates for loss of Gata-3.
AB  - Lineage commitment studies in mammary glands have focused on identifying cell
      populations that display stem or progenitor properties. However, the mechanisms
      that control cell fate have been incompletely explored. Herein we show that zinc
      finger protein 157 (Zfp157) is required to establish the balance between luminal
      alveolar pStat5- and Gata-3-expressing cells in the murine mammary gland. Using
      mice in which the zfp157 gene was disrupted, we found that alveologenesis was
      accelerated concomitantly with a dramatic skewing of the proportion of pStat5
      expressing cells relative to Gata-3+ cells. This suppression of the Gata-3+
      lineage was associated with increased expression of the inhibitor of helix-loop
      helix protein Id2. Surprisingly, Gata-3 becomes dispensable in the absence of
      Zfp157, as mice deficient for both Zfp157 and Gata-3 lactate normally, although
      the glands display a mild epithelial dysplasia. These data suggest that the
      luminal alveolar compartment of the mammary gland is comprised of a number of
      distinct cell populations that, although interdependant, exhibit considerable
      cell fate plasticity.

PMID- 22588719
TI  - Recruitment of sphingosine kinase to presynaptic terminals by a conserved
      muscarinic signaling pathway promotes neurotransmitter release.
AB  - Sphingolipids are potent lipid second messengers that regulate cell
      differentiation, migration, survival, and secretion, and alterations in
      sphingolipid signaling have been implicated in a variety of diseases. However,
      how sphingolipid levels are regulated, particularly in the nervous system,
      remains poorly understood. Here, we show that the generation of sphingosine-1
      phosphate by sphingosine kinase (SphK) promotes neurotransmitter release.
      Electrophysiological, imaging, and behavioral analyses of Caenorhabditis elegans
      mutants lacking sphingosine kinase sphk-1 indicate that neuronal development is
      normal, but there is a significant defect in neurotransmitter release from
      neuromuscular junctions. SPHK-1 localizes to discrete, nonvesicular regions
      within presynaptic terminals, and this localization is critical for synaptic
      function. Muscarinic agonists cause a rapid increase in presynaptic SPHK-1
      abundance, whereas reduction of endogenous acetylcholine production results in a
      rapid decrease in presynaptic SPHK-1 abundance. Muscarinic regulation of
      presynaptic SPHK-1 abundance is mediated by a conserved presynaptic signaling
      pathway composed of the muscarinic acetylcholine receptor GAR-3, the
      heterotrimeric G protein Galphaq, and its effector, Trio RhoGEF. SPHK-1 activity
      is required for the effects of muscarinic signaling on synaptic transmission.
      This study shows that SPHK-1 promotes neurotransmitter release in vivo and
      identifies a novel muscarinic pathway that regulates SphK abundance at
      presynaptic terminals.

PMID- 22588721
TI  - Widespread recognition of 5' splice sites by noncanonical base-pairing to U1
      snRNA involving bulged nucleotides.
AB  - An established paradigm in pre-mRNA splicing is the recognition of the 5' splice
      site (5'ss) by canonical base-pairing to the 5' end of U1 small nuclear RNA
      (snRNA). We recently reported that a small subset of 5'ss base-pair to U1 in an
      alternate register that is shifted by 1 nucleotide. Using genetic suppression
      experiments in human cells, we now demonstrate that many other 5'ss are
      recognized via noncanonical base-pairing registers involving bulged nucleotides
      on either the 5'ss or U1 RNA strand, which we term "bulge registers." By
      combining experimental evidence with transcriptome-wide free-energy calculations
      of 5'ss/U1 base-pairing, we estimate that 10,248 5'ss (~5% of human 5'ss) in 6577
      genes use bulge registers. Several of these 5'ss occur in genes with mutations
      causing genetic diseases and are often associated with alternative splicing.
      These results call for a redefinition of an essential element for gene expression
      that incorporates these registers, with important implications for the molecular
      classification of splicing mutations and for alternative splicing.

PMID- 22588722
TI  - A mechanism for the coordination of proliferation and differentiation by spatial
      regulation of Fus2p in budding yeast.
AB  - Yeast cells induce the genes required for mating prior to the completion of
      mitosis. To ensure proper cell cycle progression prior to mating differentiation,
      a key cytoplasmic regulator of cell fusion, Fus2p, is sequestered in the nucleus
      by cyclin-dependent kinase (Cdk). In response to pheromone signaling, the mitogen
      activated protein kinase Fus3p phosphorylates Ser 84 in Fus2p to drive nuclear
      export. We found that Fus3p becomes active and phosphorylates S84 as early as S
      phase, raising the question of how Cdk prevents inappropriate activation of
      Fus2p. Countering Fus3p, Cdk and a p21-activated kinase, Cla4p, maintain Fus2p's
      nuclear localization by phosphorylating Ser 67, which drives nuclear import and
      inhibits nuclear export. When Cdk and Cla4p activities drop after cell division,
      Fus3p promotes Fus2p export both via S84 phosphorylation and by down-regulating
      S67 phosphorylation. Thus, potential premature activation of Fus2p in mitosis is
      prevented by cell cycle-dependent phosphorylation that overrides the mating
      pheromone-induced phosphorylation that drives nuclear export.

PMID- 22588723
TI  - Hand-rearing and sex determination tool for the Taveta golden weaver (Ploceus
      castaneiceps).
AB  - Improvements in the ability to hand-rear birds in captivity have aided zoological
      institutions in the sustainable management of these species, and have provided
      opportunities to examine their physical growth in varying conditions. Monitoring
      the weight gain and development of chicks is an important aspect of developing a
      hand-rearing protocol. In this paper we provide the institutional history for a
      colonial species of passerine, the Taveta golden weaver, at Disney's Animal
      Kingdom(r), in order to demonstrate the methods of establishing a successful
      breeding program which largely incorporates hand-rearing in management of the
      population. We also tested if we could accurately predict sex of chicks using
      weights collected on Day 14 during the hand-rearing process. Using this tool, we
      were able to correctly determine sex before fledging in more than 83% of chicks.
      Early sex determination is important in captive species for genetic management
      and husbandry purposes. While genetic sexing can be expensive, we found that
      using growth curves to determine sex can be a reliable and cost-effective tool
      for population management of a colonial passerine.

PMID- 22588724
TI  - Decoupling two-dimensional NMR spectroscopy in both dimensions: pure shift NOESY
      and COSY.
AB  - An increase in the resolving power in 2D NMR spectra is obtained by collapsing 2D
      signals with multiplet structure into 2D singlets. This resolution gain is
      achieved by combining 2D experiments with pure shift techniques and covariance
      processing (see picture). The method should be of value in both manual and
      automated structure determination.

PMID- 22588725
TI  - Exploring the energy profile of human IgG/rat anti-human IgG interactions by
      dynamic force spectroscopy.
AB  - Interactions between antibody and antigen molecules play essential roles in
      biological recognition processes as well as medical diagnosis. Therefore, an
      understanding of the underlying mechanism of antibody-antigen interactions at the
      single molecular level would be beneficial. In the present study, human
      immunoglobulin (IgG) tethered cantilevers and rat anti-human IgG functionalized
      gold surfaces were fabricated by using self-assembled monolayers method. Dynamic
      force spectroscopy was employed to characterize the interactions between human
      (IgG) and rat anti-human IgG at the single-molecule level. The unbinding forces
      were determined to be 44.6 +/- 0.8, 65.8 +/- 3.0, 108.1 +/- 4.1, 131.1 +/- 11.2,
      149.5 +/- 4.7, 239.5 +/- 3.1 and 294.7 +/- 7.7 pN with ramping loading rates of
      514, 1,127, 3,058, 7,215, 15,286, 31,974 and 50,468 pN s(-1), respectively. In
      addition, the unbinding forces were found to be increasing with the logarithm of
      apparent loading rates in a linear way. Fitting data group resulted in two
      distinct linear parts, suggesting there are two energy barriers. The
      corresponding distances in the bound and transition states (x ( beta )) and the
      dissociation rates (K ( off )) were calculated to be 0.129 +/- 0.006 nm, 3.986 +/
      0.162 s(-1) for the outer barrier and 0.034 +/- 0.001 nm, 36.754 +/- 0.084 s(-1)
      for the inner barrier. Such findings hold promise of screening novel drugs and
      discerning different unbinding modes of biological molecules.

PMID- 22588726
TI  - In silico and in vitro analyses identified three amino acid residues critical to
      the catalysis of two aphid farnesyl diphosphate synthase.
AB  - Farnesyl diphosphate synthase (FPPS) plays an essential role in the isoprenoid
      biosynthetic pathway of microbes, plants and animals. In the present study, we
      first cloned two FPPSs from the bird cherry-oat aphid (RpFPPS1 and RpFPPS2), and
      activity assay by gas chromatography-mass spectrometry showed that both RpFPPS1
      and RpFPPS2 were active in vitro. They were then subjected to homology modeling
      and molecular docking. Molecular interaction analysis indicated that three amino
      acid residues (R120, R121 and K266) might play key roles in the catalysis of the
      two aphid FPPSs by forming hydrogen bonds with the diphosphate moiety of the
      allylic substrate. These in silico results were subsequently confirmed by site
      directed mutagenesis and in vitro activity assay of the mutant enzymes, in which
      each of the single mutations R120G, R121G and K266I abolished the activities of
      the two FPPSs. This study contributes to our understanding of the catalytic
      mechanism of farnesyl diphosphate synthases.

PMID- 22588727
TI  - Factors associated with strabismus in spina bifida myelomeningocele.
AB  - PURPOSE: Higher prevalence of strabismus in individuals with spina bifida
      myelomeningocele (SBM) has previously been attributed to hydrocephalus; however,
      SBM is associated with many other complications. This study investigates the
      relation between strabismus and other factors in SBM. METHODS: Children aged 3 to
      18 years with SBM (n = 112) received an eye examination including assessment of
      ocular alignment by cover or Hirschberg test. Gestational age, respiratory
      distress at birth, birth weight, maternal age at birth, number of shunt
      revisions, and spinal lesion level were also obtained. The relation between these
      factors and strabismus was analyzed. RESULTS: Forty-two participants had
      strabismus. Maternal age (P = .4) and respiratory distress (P = .6) were not
      significantly related to strabismus. Lower birth weight was suggestive of a
      relation with strabismus (logistic regression, P = .05) and younger gestational
      age was related to strabismus (logistic regression, P = .01). Participants who
      had at least one shunt revision were more likely to have strabismus (Fisher's
      exact test, P = .038). Spinal lesion level was significantly related to
      strabismus with increased likelihood of strabismus for spinal lesions closer to
      the brain (Wald chi-square, 1,100 = 4.29, P = .038). CONCLUSION: These findings
      indicate that several factors are associated with strabismus in SBM. Some of
      these factors (lower birth weight and younger gestational age) are associated
      with strabismus in the general population, whereas the association of strabismus
      and level of spinal lesion may be unique to SBM and may be related to the more
      severe brain dysmorphology associated with upper level spinal lesions.

PMID- 22588728
TI  - Refractive changes after pediatric intraocular lens implantation in Hong Kong
      children.
AB  - PURPOSE: To report the refractive changes after cataract surgery and intraocular
      lens (IOL) implantation in Hong Kong Chinese children. METHODS: The clinical
      records of all patients who had cataract extraction and IOL implantation before
      age 18 years and with more than 2 years of follow-up were studied
      retrospectively. The refractive errors of all patients determined by cycloplegic
      refraction at 6 weeks, 3 months, 6 months, and 1 year postoperatively and then
      annually thereafter were included for analysis. Patients were stratified into
      groups according to their age at IOL implantation for analysis. RESULTS: Twenty
      six eyes (81.3%) had developmental cataracts, 3 eyes (9.4%) had traumatic
      cataracts, and 3 eyes (9.4%) were iatrogenic (from surgical or medical
      treatment). Patients demonstrated a mean myopic shift (diopters) of -5.53 (0 to 2
      years old) -4.68 (3 to 5 years old), -2.60 (6 to 8 years old), -0.42 (9 to 11
      years), and -0.09 (> 11 years). There was no significant difference in myopic
      shift between eyes that were operated on and those that were not. No
      statistically significant differences in refractive change were found in
      comparing males to females, unilateral to bilateral cases, traumatic to non
      traumatic cases, amblyopic to nonamblyopic eyes, primary to secondary intraocular
      lenses, or polymethylmethacrylate to acrylic IOLs. CONCLUSION: The postoperative
      myopic shift in pediatric patients undergoing IOL implantation is greatest in the
      younger age groups and persists until at least 8 years of age. The mean rate of
      myopic shift also decreases with age. The refractive development of the
      pseudophakic eyes was not significantly different from the fellow phakic eyes.

PMID- 22588729
TI  - Comparison of preoperative and postoperative anterior segment measurements with
      Pentacam(r) in strabismus surgery.
AB  - PURPOSE: This study was intended to evaluate the effect of horizontal muscle
      surgery on anterior segment measurements in patients with strabismus. METHODS:
      Forty-two eyes of 28 patients with exotropia undergoing recession or recession
      combined with resection procedure were included. Consecutive cases were imaged
      using a Pentacam (Oculus, Inc., Berlin, Germany) immediately prior to surgery and
      1 and 3 months after surgery. The refractive power of the anterior surface of the
      cornea on the horizontal and vertical axis, the thinnest corneal thickness,
      anterior chamber depth, anterior chamber volume, and cornea volume were analyzed.
      The clinical characteristics of patients, visual acuity, astigmatism, and size of
      the deviations before and after surgery were reviewed. RESULTS: Muscle recession
      and recession plus resection surgery were performed in 28 and 14 eyes,
      respectively. Overall, no significant changes were noted when comparing
      preoperative and postoperative data. Patients were divided into two groups,
      recession or recession plus resection, and only anterior chamber depth was found
      to be significantly reduced in the recession group 1 month postoperatively. Three
      months postoperatively, the reduced anterior chamber depth in the recession group
      returned to the preoperative value. CONCLUSION: In this series, the recession
      procedure in patients with strabismus induced an anterior chamber depth change
      during the early postoperative period. However, the anterior chamber depth
      returned to its preoperative state by 3 months after surgery. These findings
      indicate that extraocular muscle surgery could induce reversible changes to the
      anterior segment of the eye.

PMID- 22588730
TI  - Atypical croup: association with airway lesions, atopy, and esophagitis.
AB  - OBJECTIVE: To report on airway endoscopic findings and gastrointestinal and
      atopic conditions in a large consecutive series of atypical croup. STUDY DESIGN:
      Case series with chart review. SETTING: Tertiary pediatric referral center.
      SUBJECTS AND METHODS: A surgical database was searched for all children who
      underwent full airway endoscopy to investigate atypical croup. The primary
      outcome measure was the prevalence of large airway lesions in patients with
      atypical croup undergoing endoscopy. Demographics, secondary diagnoses, and rate
      of positive findings were documented. Age and atopy were correlated using
      Spearman's correlation coefficient, and multivariate analysis identified
      predictors of large airway lesions. RESULTS: Eighty patients were identified over
      a period of 8 years (58 boys; mean [SD] age 4.8 [3.8] years; range, 46 days to
      13.7 years). Of the 80 children, 31 had positive airway findings, with 33 large
      airway lesions demonstrated, including 10 subglottic stenosis, 7 laryngeal
      clefts, 6 subglottic hemangiomas, 4 tracheomalacia, and 3 laryngomalacia.
      Esophagitis was diagnosed in 36 children, 5 of whom had eosinophilic esophagitis.
      Thirty-five children had an atopic condition including asthma, allergic rhinitis,
      eosinophilic esophagitis, and food allergies. Age correlated with associated
      atopy (coefficient 0.4, P < .0001) and predicted the presence of any airway
      lesion (coefficient -0.0625, P < .001) and subglottic stenosis in particular
      (coefficient -0.0362, P = .001). Prior intubation predicted subglottic stenosis
      (coefficient 0.267, P = .011). CONCLUSION: Thirty-nine percent of airway
      endoscopies demonstrated large airway lesions. When eosinophilic esophagitis was
      sought, it was confirmed in over 1:10 patients. The findings bolster the case for
      airway endoscopy coupled with allergy and gastrointestinal investigations.

PMID- 22588731
TI  - Three-dimensional segmented volumetric analysis of sporadic vestibular
      schwannomas: comparison of segmented and linear measurements.
AB  - OBJECTIVE: To compare 3-D segmented volumetric analysis of vestibular schwannomas
      (VS) with traditional linear tumor measurement on serial magnetic resonance
      imaging (MRI) studies to assess volume and growth rates. STUDY DESIGN: Case
      series with retrospective chart review. SETTING: Tertiary care medical center.
      METHODS: This analysis identified 24 VS patients clinically followed with serial
      gadolinium enhanced images. Maximum linear dimensions (MLD) were obtained from
      gadolinium-contrasted T1 sequences from 3 serial MRI scans per RECIST guidelines.
      MLD was cubed (MLD(3)) and orthogonal analysis (OA) was carried out to provide
      volumetric estimates for comparison with segmented data. Segmented volumetric
      analysis (SVA) was performed with semi-automated 3-D conformal procedure. Tumor
      volume, percentage change in volume, and interval percentage change were compared
      using paired 2-tailed t tests. RESULTS: The average interval between MRIs was 2.6
      years. Volume estimates differed significantly between SVA and OA and MLD(3) at
      all intervals. Linear growth measurements averaged 0.5 mm/y (5.4%). Volumetric
      growth was 50 mm(3)/y (22.8%) with SVA, 110 mm(3)/y (19.6%) with OA, and 210
      mm(3)/y (14.4%) with MLD(3) estimates. Differences between MLD and both MLD(3)
      and SVA were significant, but significance between MLD(3) and SVA was only
      identified in interval analysis. Progression was identified in 75% more patients
      with SVA than OA, MLD(3), or MLD. CONCLUSIONS: VS assume complex configurations.
      Linear measurements inaccurately estimate tumor volume and growth compared with
      segmented analysis. SVA is a useful clinical tool that accurately assesses tumor
      volume. Use of outcomes such as tumor volume and percentage of volume change may
      be more sensitive in assessing tumor progression compared with linear
      measurements.

PMID- 22588732
TI  - Human inferior turbinate: an alternative tissue source of multipotent mesenchymal
      stromal cells.
AB  - OBJECTIVE: Mesenchymal stromal cells (MSCs) are multipotent progenitor cells in
      adult tissues. Current challenges for the clinical application of MSCs include
      donor site morbidity, which underscores the need to identify alternative sources
      of MSCs. This study aimed to explore potential new sources of multipotent MSCs
      for use in tissue regeneration and the functional restoration of organs. STUDY
      DESIGN: Mixed methods research. SETTING: Tertiary care center. SUBJECTS AND
      METHODS: The authors isolated MSCs from human inferior turbinate tissues
      discarded during turbinate surgery of 10 patients for nasal obstruction. The
      expression of surface markers for MSCs was assessed by fluorescence-activated
      cell sorting. The differentiation potential of human turbinate mesenchymal
      stromal cells (hTMSCs) was analyzed by immunohistochemistry, reverse
      transcriptase-polymerase chain reaction, and Western blot analysis. RESULTS:
      Surface epitope analysis revealed that hTMSCs were negative for CD14, CD19, CD34,
      and HLA-DR and positive for CD29, CD73, and CD90, representing a characteristic
      phenotype of MSCs. Extracellular matrices with characteristics of cartilage,
      bone, and adipose tissue were produced by inducing the chondrogenic, osteogenic,
      and adipogenic differentiation of hTMSCs, respectively. The expression of neuron
      specific markers in hTMSCs was confirmed immunocytochemically. CONCLUSION: The
      hTMSCs represent a new source of multipotent MSCs that are potentially applicable
      to tissue engineering and regenerative medicine. The availability of
      differentiated adult cells will allow the development of an effective tissue
      regeneration method.

PMID- 22588733
TI  - Evidence-based medicine in otolaryngology, Part 3: everyday probabilities:
      diagnostic tests with binary results.
AB  - Recent studies have demonstrated that the majority of physicians cannot
      accurately determine the predictive values of diagnostic tests. Physicians must
      understand the predictive probabilities associated with diagnostic testing in
      order to convey accurate information to patients, a key aspect of evidence-based
      practice. While sensitivity and specificity are widely understood, predictive
      values require a further understanding of conditional probabilities, pretest
      probabilities, and the prevalence of disease. Therefore, this third installment
      of the series "Evidence-Based Medicine in Otolaryngology" focuses on
      understanding the probabilities needed to accurately convey the results of
      dichotomous diagnostic tests in everyday practice.

PMID- 22588734
TI  - Power generation capabilities of microbial fuel cells with different oxygen
      supplies in the cathodic chamber.
AB  - Two microbial fuel cells (MFCs) inoculated with activated sludge of a wastewater
      treatment plant were constructed. Oxygen was provided by mechanical aeration in
      the cathodic chamber of one MFC, whereas it was obtained by the photosynthesis of
      algae in the other. Electrogenic capabilities of both MFCs were compared under
      the same operational conditions. Results showed that the MFC with mechanical
      aeration in the cathodic chamber displayed higher power output than the one with
      photosynthesis of algae. Good linear relationship between power density and
      chemical oxygen demand (COD) loading rate was obtained only on the MFC with
      mechanical aeration. Furthermore, the relationships between power density and
      effluent COD and between Coulombic efficiency and COD loading rate can only be
      expressed as binary quadratic equations for the MFC with mechanical aeration and
      not for the one with photosynthesis of algae.

PMID- 22588735
TI  - Effect of the inducers veratryl alcohol, Xylidine, and ligninosulphonates on
      activity and thermal stability and inactivation kinetics of laccase from Trametes
      versicolor.
AB  - Laccase production from Trametes versicolor was improved in the presence of the
      inducers ligninosulphonates, veratryl alcohol, and xylidine respectively two-,
      four-, and eightfold. The thermal inactivation of the produced laccase, after
      partial purification with ammonium sulfate was kinetically investigated at
      various temperatures (60-70  degrees C) and pH values (3.5, 4.5, and 5.5). The
      inactivation process followed first-order kinetics for all conditions tested,
      except for veratryl alcohol, for which a constant activity level was observed at
      the end of the inactivation, also after first-order decay. Enzyme thermostability
      was affected by the type of inducer used in the culture medium for the production
      of laccase and also by the pH of incubation mixture. Generally, laccase stability
      increased with pH increment, being more stable at pH 5.5, except with xylidine.
      At pHs 4.5 and 5.5, the three inducers significantly increased laccase thermal
      stability, with the higher effect being observed for pH 5.5 and
      ligninosulphonates, where increment of half-life times ranged from 3- to 20-fold,
      depending on the temperature.

PMID- 22588736
TI  - Modeling the biomass growth and enzyme secretion by the white rot fungus
      Phanerochaete chrysosporium: a stochastic-based approach.
AB  - The white rot fungus Phanerochaete chrysosporium has been identified to be an
      environmentally useful microorganism for the degradation of various hazardous
      pollutants, mainly because of its ligninolytic enzyme system, particularly the
      lignin peroxidase (LiP) secreted by the fungus. In the present work, the behavior
      of the fungus in liquid medium due to variation in physico-chemical parameters,
      i.e., glucose concentration, nitrogen concentration, agitation, etc., was
      studied. Increment of the initial concentration of glucose in the medium
      increases the biomass growth and LiP activity, when cultured under controlled
      conditions. The biomass growth and LiP activity by the fungus was modeled
      following stochastic approach. The behavior of growth and enzyme activity of the
      fungus observed from the model were found to be in agreement with the experiments
      qualitatively.

PMID- 22588737
TI  - Influence of free ammonia on completely autotrophic nitrogen removal over nitrite
      (CANON) process.
AB  - Free ammonia (FA) plays a significant role in the stable, long-term, completely
      autotrophic nitrogen removal over nitrite (CANON) system operation. The influence
      of FA on the CANON process in a sequencing batch biofilm reactor was explored.
      Under controlled FA concentrations of 5.0 mg L(-1) to 10.0 mg L(-1), nitrite
      oxidizing bacteria (NOB) was inhibited and achieved partial nitrification, which
      was important for a successful and quick start-up of the CANON process from
      activated sludge. However, NOB was acclimated to the condition after the process
      start-up. Ammonia-oxidizing bacteria (AOB) and anaerobic ammonium-oxidizing
      bacteria (AnAOB) activities were unaffected when FA concentration was increased
      from 10 mg L(-1) to 17 mg L(-1), but NOB was completely inhibited only for a
      short time. The AOB and AnAOB activities were inhibited and the CANON system was
      deteriorated when FA concentration reached 30 mg L(-1) to 32.5 mg L(-1) at pH
      8.5, whereas NOB activity was unaffected. Correlation analysis showed that FA
      concentration higher than 20 mg L(-1) resulted in the deterioration of the
      system.

PMID- 22588738
TI  - Introduction to special issue: patient outcomes in rheumatology, 2011.

PMID- 22588739
TI  - Measures of disease activity and damage in pediatric systemic lupus
      erythematosus: British Isles Lupus Assessment Group (BILAG), European Consensus
      Lupus Activity Measurement (ECLAM), Systemic Lupus Activity Measure (SLAM),
      Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), Physician's Global
      Assessment of Disease Activity (MD Global), and Systemic Lupus International
      Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR
      DI; SDI).

PMID- 22588741
TI  - Measures of rheumatoid arthritis disease activity: Patient (PtGA) and Provider
      (PrGA) Global Assessment of Disease Activity, Disease Activity Score (DAS) and
      Disease Activity Score with 28-Joint Counts (DAS28), Simplified Disease Activity
      Index (SDAI), Clinical Disease Activity Index (CDAI), Patient Activity Score
      (PAS) and Patient Activity Score-II (PASII), Routine Assessment of Patient Index
      Data (RAPID), Rheumatoid Arthritis Disease Activity Index (RADAI) and Rheumatoid
      Arthritis Disease Activity Index-5 (RADAI-5), Chronic Arthritis Systemic Index
      (CASI), Patient-Based Disease Activity Score With ESR (PDAS1) and Patient-Based
      Disease Activity Score without ESR (PDAS2), and Mean Overall Index for Rheumatoid
      Arthritis (MOI-RA).

PMID- 22588742
TI  - Measures of function in low back pain/disorders: Low Back Pain Rating Scale
      (LBPRS), Oswestry Disability Index (ODI), Progressive Isoinertial Lifting
      Evaluation (PILE), Quebec Back Pain Disability Scale (QBPDS), and Roland-Morris
      Disability Questionnaire (RDQ).

PMID- 22588740
TI  - Measures of adult and juvenile dermatomyositis, polymyositis, and inclusion body
      myositis: Physician and Patient/Parent Global Activity, Manual Muscle Testing
      (MMT), Health Assessment Questionnaire (HAQ)/Childhood Health Assessment
      Questionnaire (C-HAQ), Childhood Myositis Assessment Scale (CMAS), Myositis
      Disease Activity Assessment Tool (MDAAT), Disease Activity Score (DAS), Short
      Form 36 (SF-36), Child Health Questionnaire (CHQ), physician global damage,
      Myositis Damage Index (MDI), Quantitative Muscle Testing (QMT), Myositis
      Functional Index-2 (FI-2), Myositis Activities Profile (MAP), Inclusion Body
      Myositis Functional Rating Scale (IBMFRS), Cutaneous Dermatomyositis Disease Area
      and Severity Index (CDASI), Cutaneous Assessment Tool (CAT), Dermatomyositis Skin
      Severity Index (DSSI), Skindex, and Dermatology Life Quality Index (DLQI).

PMID- 22588743
TI  - Measures of adult shoulder function: Disabilities of the Arm, Shoulder, and Hand
      Questionnaire (DASH) and its short version (QuickDASH), Shoulder Pain and
      Disability Index (SPADI), American Shoulder and Elbow Surgeons (ASES) Society
      standardized shoulder assessment form, Constant (Murley) Score (CS), Simple
      Shoulder Test (SST), Oxford Shoulder Score (OSS), Shoulder Disability
      Questionnaire (SDQ), and Western Ontario Shoulder Instability Index (WOSI).

PMID- 22588744
TI  - Measures of hand function: Arthritis Hand Function Test (AHFT), Australian
      Canadian Osteoarthritis Hand Index (AUSCAN), Cochin Hand Function Scale,
      Functional Index for Hand Osteoarthritis (FIHOA), Grip Ability Test (GAT), Jebsen
      Hand Function Test (JHFT), and Michigan Hand Outcomes Questionnaire (MHQ).

PMID- 22588745
TI  - Measures of hip function and symptoms: Harris Hip Score (HHS), Hip Disability and
      Osteoarthritis Outcome Score (HOOS), Oxford Hip Score (OHS), Lequesne Index of
      Severity for Osteoarthritis of the Hip (LISOH), and American Academy of
      Orthopedic Surgeons (AAOS) Hip and Knee Questionnaire.

PMID- 22588746
TI  - Measures of knee function: International Knee Documentation Committee (IKDC)
      Subjective Knee Evaluation Form, Knee Injury and Osteoarthritis Outcome Score
      (KOOS), Knee Injury and Osteoarthritis Outcome Score Physical Function Short Form
      (KOOS-PS), Knee Outcome Survey Activities of Daily Living Scale (KOS-ADL),
      Lysholm Knee Scoring Scale, Oxford Knee Score (OKS), Western Ontario and McMaster
      Universities Osteoarthritis Index (WOMAC), Activity Rating Scale (ARS), and
      Tegner Activity Score (TAS).

PMID- 22588748
TI  - Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating
      Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill
      Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36
      Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant
      Osteoarthritis Pain (ICOAP).

PMID- 22588747
TI  - Measures of foot function, foot health, and foot pain: American Academy of
      Orthopedic Surgeons Lower Limb Outcomes Assessment: Foot and Ankle Module (AAOS
      FAM), Bristol Foot Score (BFS), Revised Foot Function Index (FFI-R), Foot Health
      Status Questionnaire (FHSQ), Manchester Foot Pain and Disability Index (MFPDI),
      Podiatric Health Questionnaire (PHQ), and Rowan Foot Pain Assessment (ROFPAQ).

PMID- 22588749
TI  - Measures of pediatric pain: 21-numbered circle Visual Analog Scale (VAS), E-Ouch
      Electronic Pain Diary, Oucher, Pain Behavior Observation Method, Pediatric Pain
      Assessment Tool (PPAT), and Pediatric Pain Questionnaire (PPQ).

PMID- 22588750
TI  - Measures of fatigue: Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional
      Questionnaire (BRAF MDQ), Bristol Rheumatoid Arthritis Fatigue Numerical Rating
      Scales (BRAF NRS) for severity, effect, and coping, Chalder Fatigue Questionnaire
      (CFQ), Checklist Individual Strength (CIS20R and CIS8R), Fatigue Severity Scale
      (FSS), Functional Assessment Chronic Illness Therapy (Fatigue) (FACIT-F), Multi
      Dimensional Assessment of Fatigue (MAF), Multi-Dimensional Fatigue Inventory
      (MFI), Pediatric Quality Of Life (PedsQL) Multi-Dimensional Fatigue Scale,
      Profile of Fatigue (ProF), Short Form 36 Vitality Subscale (SF-36 VT), and Visual
      Analog Scales (VAS).

PMID- 22588752
TI  - Measures of adult general functional status: SF-36 Physical Functioning Subscale
      (PF-10), Health Assessment Questionnaire (HAQ), Modified Health Assessment
      Questionnaire (MHAQ), Katz Index of Independence in activities of daily living,
      Functional Independence Measure (FIM), and Osteoarthritis-Function-Computer
      Adaptive Test (OA-Function-CAT).

PMID- 22588751
TI  - Measures of sleep in rheumatologic diseases: Epworth Sleepiness Scale (ESS),
      Functional Outcome of Sleep Questionnaire (FOSQ), Insomnia Severity Index (ISI),
      and Pittsburgh Sleep Quality Index (PSQI).

PMID- 22588753
TI  - Measures of disability: Arthritis Impact Measurement Scales 2 (AIMS2), Arthritis
      Impact Measurement Scales 2-Short Form (AIMS2-SF), The Organization for Economic
      Cooperation and Development (OECD) Long-Term Disability (LTD) Questionnaire, EQ
      5D, World Health Organization Disability Assessment Schedule II (WHODASII), Late
      Life Function and Disability Instrument (LLFDI), and Late-Life Function and
      Disability Instrument-Abbreviated Version (LLFDI-Abbreviated).

PMID- 22588754
TI  - Measures of social function and participation in musculoskeletal populations:
      Impact on Participation and Autonomy (IPA), Keele Assessment of Participation
      (KAP), Participation Measure for Post-Acute Care (PM-PAC), Participation
      Objective, Participation Subjective (POPS), Rating of Perceived Participation
      (ROPP), and The Participation Scale.

PMID- 22588755
TI  - Measures of work disability and productivity: Rheumatoid Arthritis Specific Work
      Productivity Survey (WPS-RA), Workplace Activity Limitations Scale (WALS), Work
      Instability Scale for Rheumatoid Arthritis (RA-WIS), Work Limitations
      Questionnaire (WLQ), and Work Productivity and Activity Impairment Questionnaire
      (WPAI).

PMID- 22588756
TI  - Measures of physical performance assessments: Self-Paced Walk Test (SPWT), Stair
      Climb Test (SCT), Six-Minute Walk Test (6MWT), Chair Stand Test (CST), Timed Up &
      Go (TUG), Sock Test, Lift and Carry Test (LCT), and Car Task.

PMID- 22588758
TI  - Measures of pediatric function: Child Health Assessment Questionnaire (C-HAQ),
      Juvenile Arthritis Functional Assessment Scale (JAFAS), Pediatric Outcomes Data
      Collection Instrument (PODCI), and Activities Scale for Kids (ASK).

PMID- 22588757
TI  - Measures of adult systemic lupus erythematosus: updated version of British Isles
      Lupus Assessment Group (BILAG 2004), European Consensus Lupus Activity
      Measurements (ECLAM), Systemic Lupus Activity Measure, Revised (SLAM-R), Systemic
      Lupus Activity Questionnaire for Population Studies (SLAQ), Systemic Lupus
      Erythematosus Disease Activity Index 2000 (SLEDAI-2K), and Systemic Lupus
      International Collaborating Clinics/American College of Rheumatology Damage Index
      (SDI).

PMID- 22588759
TI  - Adult measures of general health and health-related quality of life: Medical
      Outcomes Study Short Form 36-Item (SF-36) and Short Form 12-Item (SF-12) Health
      Surveys, Nottingham Health Profile (NHP), Sickness Impact Profile (SIP), Medical
      Outcomes Study Short Form 6D (SF-6D), Health Utilities Index Mark 3 (HUI3),
      Quality of Well-Being Scale (QWB), and Assessment of Quality of Life (AQoL).

PMID- 22588760
TI  - Measures of functional status and quality of life in rheumatoid arthritis: Health
      Assessment Questionnaire Disability Index (HAQ), Modified Health Assessment
      Questionnaire (MHAQ), Multidimensional Health Assessment Questionnaire (MDHAQ),
      Health Assessment Questionnaire II (HAQ-II), Improved Health Assessment
      Questionnaire (Improved HAQ), and Rheumatoid Arthritis Quality of Life (RAQoL).

PMID- 22588761
TI  - Health-related quality of life measurement in adult systemic lupus erythematosus:
      Lupus Quality of Life (LupusQoL), Systemic Lupus Erythematosus-Specific Quality
      of Life Questionnaire (SLEQOL), and Systemic Lupus Erythematosus Quality of Life
      Questionnaire (L-QoL).

PMID- 22588762
TI  - Measures of general pediatric quality of life: Child Health Questionnaire (CHQ),
      DISABKIDS Chronic Generic Measure (DCGM), KINDL-R, Pediatric Quality of Life
      Inventory (PedsQL) 4.0 Generic Core Scales, and Quality of My Life Questionnaire
      (QoML).

PMID- 22588763
TI  - Measures of juvenile fibromyalgia: Functional Disability Inventory (FDI),
      Modified Fibromyalgia Impact Questionnaire-Child Version (MFIQ-C), and Pediatric
      Quality of Life Inventory (PedsQL) 3.0 Rheumatology Module Pain and Hurt Scale.

PMID- 22588764
TI  - Measures of health status and quality of life in juvenile rheumatoid arthritis:
      Pediatric Quality of Life Inventory (PedsQL) Rheumatology Module 3.0, Juvenile
      Arthritis Quality of Life Questionnaire (JAQQ), Paediatric Rheumatology Quality
      of Life Scale (PRQL), and Childhood Arthritis Health Profile (CAHP).

PMID- 22588765
TI  - Measures of health-related quality of life in pediatric systemic lupus
      erythematosus: Childhood Health Assessment Questionnaire (C-HAQ), Child Health
      Questionnaire (CHQ), Pediatric Quality of Life Inventory Generic Core Module
      (PedsQL-GC), Pediatric Quality of Life Inventory Rheumatology Module (PedsQL-RM),
      and Simple Measure of Impact of Lupus Erythematosus in Youngsters (SMILEY).

PMID- 22588766
TI  - Measures of depression and depressive symptoms: Beck Depression Inventory-II (BDI
      II), Center for Epidemiologic Studies Depression Scale (CES-D), Geriatric
      Depression Scale (GDS), Hospital Anxiety and Depression Scale (HADS), and Patient
      Health Questionnaire-9 (PHQ-9).

PMID- 22588767
TI  - Measures of anxiety: State-Trait Anxiety Inventory (STAI), Beck Anxiety Inventory
      (BAI), and Hospital Anxiety and Depression Scale-Anxiety (HADS-A).

PMID- 22588768
TI  - Measures of symptoms and disease status in ankylosing spondylitis: Ankylosing
      Spondylitis Disease Activity Score (ASDAS), Ankylosing Spondylitis Quality of
      Life Scale (ASQoL), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI),
      Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis
      Global Score (BAS-G), Bath Ankylosing Spondylitis Metrology Index (BASMI),
      Dougados Functional Index (DFI), and Health Assessment Questionnaire for the
      Spondylarthropathies (HAQ-S).

PMID- 22588769
TI  - Measures of self-efficacy: Arthritis Self-Efficacy Scale (ASES), Arthritis Self
      Efficacy Scale-8 Item (ASES-8), Children's Arthritis Self-Efficacy Scale (CASE),
      Chronic Disease Self-Efficacy Scale (CDSES), Parent's Arthritis Self-Efficacy
      Scale (PASE), and Rheumatoid Arthritis Self-Efficacy Scale (RASE).

PMID- 22588770
TI  - The future of measuring patient-reported outcomes in rheumatology: Patient
      Reported Outcomes Measurement Information System (PROMIS).

PMID- 22588771
TI  - Gout measures: Gout Assessment Questionnaire (GAQ, GAQ2.0), and physical
      measurement of tophi.

PMID- 22588772
TI  - Measures of psoriatic arthritis: Tender and Swollen Joint Assessment, Psoriasis
      Area and Severity Index (PASI), Nail Psoriasis Severity Index (NAPSI), Modified
      Nail Psoriasis Severity Index (mNAPSI), Mander/Newcastle Enthesitis Index (MEI),
      Leeds Enthesitis Index (LEI), Spondyloarthritis Research Consortium of Canada
      (SPARCC), Maastricht Ankylosing Spondylitis Enthesis Score (MASES), Leeds
      Dactylitis Index (LDI), Patient Global for Psoriatic Arthritis, Dermatology Life
      Quality Index (DLQI), Psoriatic Arthritis Quality of Life (PsAQOL), Functional
      Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Psoriatic Arthritis
      Response Criteria (PsARC), Psoriatic Arthritis Joint Activity Index (PsAJAI),
      Disease Activity in Psoriatic Arthritis (DAPSA), and Composite Psoriatic Disease
      Activity Index (CPDAI).

PMID- 22588773
TI  - Measures of fibromyalgia: Fibromyalgia Impact Questionnaire (FIQ), Brief Pain
      Inventory (BPI), Multidimensional Fatigue Inventory (MFI-20), Medical Outcomes
      Study (MOS) Sleep Scale, and Multiple Ability Self-Report Questionnaire (MASQ).

PMID- 22588774
TI  - Measures of systemic sclerosis (scleroderma): Health Assessment Questionnaire
      (HAQ) and Scleroderma HAQ (SHAQ), physician- and patient-rated global
      assessments, Symptom Burden Index (SBI), University of California, Los Angeles,
      Scleroderma Clinical Trials Consortium Gastrointestinal Scale (UCLA SCTC GIT)
      2.0, Baseline Dyspnea Index (BDI) and Transition Dyspnea Index (TDI) (Mahler's
      Index), Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR), and Raynaud's
      Condition Score (RCS).

PMID- 22588775
TI  - Programmable genetic switches to control transcriptional machinery of
      pluripotency.
AB  - Transcriptional activators play a central role in the regulation of gene
      expression and have the ability to manipulate the specification of cell fate.
      Pluripotency is a transient state where a cell has the potential to develop into
      more than one type of mature cell. The induction of pluripotency in
      differentiated cells requires extensive chromatin reorganization regulated by
      core transcriptional machinery. Several small molecules have been shown to
      enhance the efficiency of somatic cell reprogramming into pluripotent stem cells.
      However, entirely chemical-based reprogramming remains elusive. Recently, we
      reported that selective DNA-binding hairpin pyrrole-imidazole polyamides
      conjugated with histone deacetylase inhibitor could mimic natural transcription
      factors and epigenetically activate certain pluripotency-associated genes. Here,
      we review the need to develop selective chromatin-modifying transcriptional
      activators for somatic genome reprogramming.

PMID- 22588776
TI  - Adalimumab for refractory peripheral ulcerative keratitis.

PMID- 22588777
TI  - Probable Vogt-Koyanagi-Harada disease with initial unilateral ocular
      manifestation in a hepatitis C carrier.

PMID- 22588778
TI  - Molecular and genetic bases of neuroblastoma.
AB  - Neuroblastoma, which is derived from the sympathetic nervous system, is the
      second most common pediatric solid malignant tumor. This pediatric tumor has a
      heterogeneous course, ranging from spontaneous regression to inexorable
      progression and death, depending on the biological features of the tumor.
      Identification of risk groups on the basis of clinical and molecular prognostic
      variables has allowed tailor-made therapy to improve outcomes and minimize the
      risk of deleterious consequences of therapy. In Japan, current therapeutic
      stratification of patients with neuroblastoma is based on risk assessment
      according to combinations of age, tumor stage, MYCN status, DNA ploidy status,
      and histopathology; however, unfavorable neuroblastoma is still one of the most
      difficult tumors to cure, with only 40 % long-term survival despite intensive
      multimodal therapy. Further refined therapeutic stratification based on newly
      identified prognostic factors will be required to improve the outcome of patients
      with unfavorable neuroblastoma and reduce the side effects of therapies for
      patients with favorable neuroblastoma. In the present review, we describe recent
      topics on the molecular and genetic bases of neuroblastoma; we hope this review
      will be helpful for understanding the mechanism of neuroblastoma tumorigenesis
      and aggressiveness and for developing a new therapeutic stratification and new
      protocols for neuroblastoma treatments.

PMID- 22588780
TI  - Sentinel lymph node biopsy after neoadjuvant chemotherapy predicts pathological
      axillary lymph node status in breast cancer patients with clinically positive
      axillary lymph nodes at presentation.
AB  - BACKGROUND: It is still controversial whether axillary lymph node (ALN)
      dissection (ALND) can be omitted after negative sentinel lymph node (SLN) biopsy
      (SLNB) in breast cancer (BC) patients with clinically positive ALNs at
      presentation treated with neoadjuvant chemotherapy (NAC). The study aim was to
      analyze whether SLNB could be useful in these patients. METHODS: In a
      retrospective study, eligible patients were women with invasive BC with
      clinically positive ALNs at presentation, treated with NAC then a total or
      partial mastectomy, with an intraoperative histological examination of SLNs and
      non-SLNs suspicious for metastasis followed by ALND. Non-SLNs suspicious for
      metastasis were defined as hard or large nodes located in the same level of the
      axilla where clinically positive ALNs had been initially identified. The results
      of SLNB and clinicopathological characteristics were analyzed for correlation
      with pathological ALN status. RESULTS: In a consecutive series of 105 women with
      107 BC cases, 81 (75.7 %) had at least 1 SLN, and the remaining 26 (24.3 %) had
      at least 1 non-SLN suspicious for metastasis. The intraoperative (or final)
      histological examination of these nodes revealed that the false-negative (FN)
      rate and accuracy were 8.2 (or 6.3) % and 95.1 (or 96.3) %, respectively.
      Estrogen receptor status at presentation, pathological tumor response,
      lymphovascular invasion after NAC, and NAC regimen were correlated with
      pathological ALN status. CONCLUSION: The histological examination of SLNs and
      that of non-SLNs suspicious for metastasis are useful for predicting pathological
      ALN status in BC patients with clinically positive ALNs at presentation who are
      treated with NAC.

PMID- 22588779
TI  - Development of treatment strategies for advanced neuroblastoma.
AB  - Neuroblastoma is the most common cancer in childhood. The majority of patients
      with neuroblastoma are assigned to the high-risk group based on age at diagnosis,
      stage, histology, MYCN status, and DNA ploidy. Their prognosis remains
      unsatisfactory; the 5-year event-free survival (EFS) rate is generally 40 %.
      During the past 20 years, much effort has been made to reinforce chemotherapy,
      including the introduction of high-dose chemotherapy with autologous stem cell
      rescue, resulting in a 5-year EFS rate of around 30 %. Subsequently, maintenance
      therapy aimed at eradicating residual tumors after induction and consolidation
      therapies was introduced, consisting of differentiation-inducing agents,
      retinoids, and immunotherapy using anti-GD2 antibodies combined with cytokines.
      However, such additional treatment provided benefit to only 10-20 % of patients,
      while the prognosis of about half the patients remains poor. Currently, novel
      targeted agents are under development. Among them, anaplastic lymphoma kinase
      (ALK) inhibitors and aurora kinase A inhibitors are promising. ALK somatic
      mutation or gene amplification predisposing neuroblastoma development occurs in
      up to 15 % of neuroblastomas. Crizotinib is a dual-specific inhibitor of ALK/Met
      and inhibits proliferation of neuroblastoma cells harboring R1275Q-mutated ALK or
      amplified wild-type ALK, but not cells harboring F1174L. Instead, cells with
      F1174L are sensitive to another small molecule ALK inhibitor, TAE684. Aurora
      kinase A plays a pivotal role in centrosome maturation and spindle formation
      during mitosis. MLN8237 (alisertib) is a small molecule inhibitor of aurora
      kinase A that is currently in early-phase clinical testing. Future treatment will
      be individually planned, adapting targeted agents based on personal biological
      tumor characteristics.

PMID- 22588781
TI  - The contribution of neck dissection for residual neck disease after
      chemoradiotherapy in advanced oropharyngeal and hypopharyngeal squamous cell
      carcinoma patients.
AB  - BACKGROUND: Planned neck dissection after chemoradiotherapy (CRT) has remained
      controversial in advanced oro- and hypopharyngeal squamous cell carcinoma (OHSCC)
      patients. We evaluated the survival contribution of neck dissection (ND) in OHSCC
      patients with residual nodal disease following CRT. METHODS: We retrospectively
      evaluated 84 OHSCC patients with N2-3 disease treated at Aichi Cancer Center
      Hospital between 1995 and 2006. ND after CRT was performed for residual neck
      disease in 36 patients, but not in 48 patients to achieve a complete response.
      These two groups were analyzed in terms of both overall survival (OS) and
      regional control (RC), and surgical complications were evaluated. RESULTS: The 5
      year OS was 76.7 % [95 % confidence interval (CI) 58.8-87.6] for the ND group and
      73.9 % (58.6-84.3) for the non-ND group (P = 0.883). The 5-year RC was 91.6 %
      (76.1-97.2) for the ND group and 81.1 % (65.4-90.2) for the non-ND group (P =
      0.252). Stratified by primary tumor site, the 5-year RC was 96.3 % (76.5-99.5)
      for the ND group, and 78.6 % (58.0-89.9) for the non-ND group (P = 0.072) in
      oropharyngeal squamous cell carcinoma patients, and 77.8 % (36.5-93.9) for the ND
      group and 85.9 % (54.0-96.3) for the non-ND group (P = 0.541) in hypopharyngeal
      squamous cell carcinoma patients. In addition, the complications after ND were
      tolerable. CONCLUSIONS: We demonstrated that ND was feasible, safe, and
      correlated with clinical outcomes in OHSCC patients with residual nodal disease
      after CRT.

PMID- 22588782
TI  - Current status of molecular biology and treatment strategy for neuroblastoma.

PMID- 22588783
TI  - Opposing influences of ruffling and doming deformation on the 4-N cavity size of
      porphyrin macrocycles: the role of heme deformations revealed.
AB  - Ruffle- and dome-type porphyrins were developed as model systems to investigate
      the role of deformation mode and degree of distortion in heme. Their crystal
      structures revealed that as the degree of distortion increases, cavity size can
      be contracted in the ruffle mode and expanded in the dome mode, and the size of
      cavity can exceed the limit of free metal ions from the fourth period (see
      scheme).

PMID- 22588784
TI  - Modeling of hysteresis in gene regulatory networks.
AB  - Hysteresis, observed in many gene regulatory networks, has a pivotal impact on
      biological systems, which enhances the robustness of cell functions. In this
      paper, a general model is proposed to describe the hysteretic gene regulatory
      network by combining the hysteresis component and the transient dynamics. The
      Bouc-Wen hysteresis model is modified to describe the hysteresis component in the
      mammalian gene regulatory networks. Rigorous mathematical analysis on the
      dynamical properties of the model is presented to ensure the bounded-input
      bounded-output (BIBO) stability and demonstrates that the original Bouc-Wen model
      can only generate a clockwise hysteresis loop while the modified model can
      describe both clockwise and counter clockwise hysteresis loops. Simulation
      studies have shown that the hysteresis loops from our model are consistent with
      the experimental observations in three mammalian gene regulatory networks and two
      E.coli gene regulatory networks, which demonstrate the ability and accuracy of
      the mathematical model to emulate natural gene expression behavior with
      hysteresis. A comparison study has also been conducted to show that this model
      fits the experiment data significantly better than previous ones in the
      literature. The successful modeling of the hysteresis in all the five hysteretic
      gene regulatory networks suggests that the new model has the potential to be a
      unified framework for modeling hysteresis in gene regulatory networks and provide
      better understanding of the general mechanism that drives the hysteretic
      function.

PMID- 22588785
TI  - Master-slave robotic platform and its feasibility study for micro-neurosurgery.
AB  - BACKGROUND: Microsurgery is a widely performed process in neurosurgery. However,
      it is difficult for surgeons because manipulating small and long instruments
      under a microscope often restricts dexterity. Hand tremors are also an issue, as
      the accuracy required for microsurgery is very high. METHOD: A master-slave
      robotic platform has been developed for neurosurgery. A position-orientation
      decoupled design was employed to enhance positioning accuracy, and a smooth
      trajectory generation method was developed. RESULT: The robotic tasks exhibited
      improved positioning accuracy compared to manual tasks. Anastomoses of 0.3 and
      0.5 mm artificial vessels were successfully performed in end-to-end and end-to
      side fashion. CONCLUSION: With the robotic platform, the surgeon was able to
      perform a fine and complex task, which is very difficult with manual operation.
      The robotic system showed sufficient accuracy and dexterity, but with a longer
      task completion time. Further improvement of the dexterity and user interface is
      expected to realize better performance.

PMID- 22588787
TI  - Dynamic electrochemistry in flame plasma electrolyte.
AB  - Chemistry in flames: Dynamic electrochemistry in the gas phase is described by
      considering the ionized medium of a flame as an electrolyte (see picture). This
      study opens up the possibility of accessing redox reactions that are outside the
      potential limits set by the solvent in conventional liquid-phase
      electrochemistry.

PMID- 22588786
TI  - Effects of di(2-ethylhexyl) phthalate (DEHP) on female fertility and adipogenesis
      in C3H/N mice.
AB  - BACKGROUND: Di(2-ethylhexyl) phthalate (DEHP) and its metabolites are known to
      affect lipid metabolism and adipogenesis, mainly by activation of peroxisome
      proliferator-activated receptors (PPARs). Exposure to DEHP has been linked with
      testicular impairment and male subfertility. However, the effects of DEHP on
      female reproductive health and metabolism have not been studied in detail.
      OBJECTIVE: We examined the effects of dietary DEHP exposure on metabolism and
      fertility in female mice. METHODS: In two independent approaches, female C3H/N
      mice were exposed to DEHP (0.05, 5, or 500 mg/kg of body weight per day) via
      their diet for 8 weeks, and we recorded food intake, weight gain, and litter
      size. After exposure, liver, visceral fat, and plasma from F0 females (study I)
      and F0 dams and their F1 offspring (study II) were analyzed by quantitative real
      time polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: In
      study I, DEHP-exposed F0 females (all dose groups) had a significant increase in
      body weight, food intake, and visceral adipose tissue compared with controls. In
      the 500-mg DEHP group, PPARalpha and PPARgamma transcripts were significantly
      changed in liver tissue. In the same group, PPARgamma mRNA was significantly
      reduced in liver but not in fat tissue. In addition, leptin and FABP4 (fatty acid
      binding protein 4) mRNA were increased in adipose tissue, whereas adiponectin was
      decreased. In study II, we detected a 100% abortion rate in F0 dams in the 500-mg
      group. F1 offspring exposed in utero and during lactation had an increase in
      visceral fat tissue and body weight. CONCLUSION: Fertility was impaired in mice
      exposed to high doses of DEHP, and body weight and visceral fat deposits were
      increased in mice exposed to environmentally relevant doses. Although F1 mice
      were exposed to DEHP only in utero and during lactation, we observed metabolic
      changes in the offspring of diet-exposed females.

PMID- 22588788
TI  - High molecular weight calmodulin-binding protein: 20 years onwards-a potential
      therapeutic calpain inhibitor.
AB  - Apoptosis in cardiovascular diseases is considered to be a major reason for heart
      failure. Caspase-independent apoptosis due to calpains and other proteases occurs
      due to increase in intracellular Ca(2+) levels which act on a feed-forward
      mechanism. Calpains are Ca(2+)-activated cysteine proteases present in the
      cytosol as inactive proenzymes. Calpastatin is most efficient and specific
      calpain inhibitor present in vivo. Earlier, we had reported the expression of
      novel high molecular weight calmodulin-binding protein (HMWCaMBP) in human and
      animal cardiac tissue and in very minute quantities in brains and lungs. HMWCaMBP
      showed calpastatin activity and was also found to be highly homologous to
      calpastatin I and calpastatin II. Decreased expression of HMWCaMBP was observed
      during ischemia as it is susceptible to proteolysis by calpains during ischemia
      reperfusion. In normal myocardium, HMWCaMBP may protect its substrate from
      calpains. However, during an early stage of ischemia/reperfusion due to increased
      Ca(2+) influx, calpain activity often exceeds HMWCaMBP activity. This leads to
      proteolysis of HMWCaMBP and other protein substrates, resulting in cellular
      damage. The role of HMWCaMBP in ischemia/reperfusion is yet to be elucidated. The
      present review summarizes the developments in area of HMWCaMBP from the authors'
      laboratory and its potential for therapy.

PMID- 22588789
TI  - ADHD in adults: a concept in evolution.
AB  - Although attention-deficit/hyperactivity disorder (ADHD) has been recognized as a
      disorder affecting individuals across the life cycle since the end of the
      nineties, there is still considerable debate on how to conceptualize the disorder
      in adults, and on the best way to operationalize diagnostic criteria for this age
      range. In this comprehensive non-systematic review of the literature, we provide
      data about prevalence and presentation of ADHD in adulthood as well as discuss
      major problems in applying criteria developed for children in assessing adults
      (clinical utility, threshold of symptoms for diagnosis, full ADHD diagnosis in
      childhood, information source, and additional dimensions for diagnosis-executive
      functioning impairment and emotional impulsivity). In addition, we provide some
      recommendations for improving ADHD diagnostic criteria in adulthood.

PMID- 22588790
TI  - Fractional exhaled nitric oxide in healthy non-asthmatic 7-year olds and prenatal
      exposure to polycyclic aromatic hydrocarbons: nested regression analysis.
AB  - The main goal of the study was to assess possible association between
      transplacental exposure to genotoxic PAH compounds assessed by the cord blood PAH
      DNA adducts and fractional exhaled nitric oxide (FeNO) measured in healthy non
      asthmatic children at the age of 7 years. The subjects included the subsample of
      89 children who took part in the ongoing population based birth cohort study in
      Krakow and attended FeNO testing. The effect of transplacental PAH exposure was
      adjusted for potential confounders, such as maternal allergy and children's
      specific atopy to common domestic allergens. RESULTS: FeNO values were
      significantly elevated in children with higher prenatal PAH exposure (gmean = 7.7
      ppb; 95% CI: 5.8-10.2 ppb) compared with those at low exposure level (gmean = 3.8
      ppb; 95% CI: 2.3-6.3) (P = 0.011). Children with maternal allergy had also
      significantly higher mean FeNO values (gmean = 13.7 ppb, 95% CI: 8.8-21.4 ppb)
      compared with the subjects whose mothers denied allergy (gmean = 5.6 ppb, 95% CI:
      4.3-7.3 ppb) (P = 0.012). Similarly, FeNO values in atopic children were higher
      (gmean = 11.2 ppb; 95% CI: 3.8-32.8 ppb) than in non-atopic individuals (gmean =
      6.0 ppb; 95% CI: 4.7-7.7 ppb, P = 0.079). The results of the nested multivariable
      linear regression analysis showed that both maternal allergy and sensitization of
      children to domestic aeroallergens jointly explained 10.4% of FeNO variance,
      however, the additional 10.9% was determined by prenatal PAH exposure.
      CONCLUSION: FeNO is more than a marker useful for screening atopy or symptomatic
      bronchial inflammation and may also be a proxy for cytokine deregulation and
      "allergic response" phenotype possibly established in fetal period due to
      transplacental PAH exposure. Preliminary results of our study should encourage
      more studies on intrauterine PAH exposure and later respiratory symptoms.

PMID- 22588791
TI  - The anatomic basis of the profunda femoris artery perforator flap: a new option
      for autologous breast reconstruction--a cadaveric and computer tomography
      angiogram study.
AB  - We propose the profunda femoris artery perforator (PAP) flap for autologous
      breast reconstruction. We provide an anatomic basis for this flap. Ten cadaveric
      thighs were dissected. A perforator was dissected to its origin. The lengths of
      pedicle, vessel diameters, and weights were measured. The average distance
      inferior to the gluteal crease was 3.5 cm (1 to 5 cm). The average distance from
      the midline was 6.2 cm (3 to 12 cm). The average pedicle length was 10.6 cm.
      Diameters of the artery and vein averaged 2.3 mm and 2.8 mm. The flaps averaged
      28 * 8 cm. The average weight was 206 g (100 to 260 g). Computed tomography
      angiograms of 20 thighs were examined. Measurements were taken from the gluteal
      crease and midline to the perforator. The average distance caudal to the gluteal
      crease was 4.4 cm (1.1 to 7.2 cm). The average distance lateral to the midline
      was 5.1 cm (2.5 to 9 cm). The data presented in this article provide an anatomic
      basis for the PAP flap.

PMID- 22588792
TI  - Supplementing technique training for the learner microsurgeon.

PMID- 22588793
TI  - Effect of neurotization upon degree of sensory recovery in toe-to-hand
      microvascular transplantation.
AB  - The relationship between the number of myelinated nerve fibers from the hand that
      are reinnervating the distal glabrous skin of the toe and the number of
      myelinating nerve fibers originally innervating that toe target was investigated
      utilizing the toe-to-hand microvascular transplantation model. Digital nerve
      biopsy specimens suitable for morphometric analysis were obtained from the hand
      and toe at the time of surgery from 15 patients. Patients received sensory
      reeducation in the postoperative period to standardize rehabilitation. At a mean
      of 10.8 months after surgery, the degree of sensory recovery was determined by
      the hand therapist. Morphometric analysis was done by a neurologist blinded as to
      final sensory outcome. There was a statistically significant relationship between
      recovered moving two-point discrimination and ratio of the total number of
      reinnervating (neurotizing) finger axons compared with the original toe axons (r
      = 0.703, p < 0.003). A similar relationship was observed for static two-point
      discrimination (r = 0.802, p < 0.001). These results suggest that degree of
      sensory recovery in toe-to-hand transfer may be improved by increasing the number
      of reinnervating myelinated nerve fibers from the hand that neurotizes the free
      tissue transfer.

PMID- 22588794
TI  - Fasciocutaneous free flaps are more reliable than muscle free flaps in lower limb
      trauma reconstruction: experience in a single trauma center.
AB  - BACKGROUND: Muscle (M) and fasciocutaneous (FC) free flaps are frequently used
      options in the reconstruction of traumatic lower limb injuries. The use of one
      flap over another has remained the topic of controversy in the literature. With a
      large experience, we sought to evaluate key outcomes of M versus FC free flap
      reconstructions in lower limb trauma in a single trauma center. METHODS: A
      consecutive 7- year review of all free flap reconstructions for lower limb trauma
      performed at the Royal Melbourne Hospital was conducted. Patient data were
      prospectively entered into a unit database and retrospectively reviewed. RESULTS:
      One hundred three patients underwent 105 free flap reconstructions (M = 48 and FC
      = 57) in lower limb trauma. We experienced a rate of 2.9% total flap failures and
      11.4% partial flap losses. Total flap failures represented 6.3% M and 0% FC
      flaps. The partial flap failures included 15.8% of M and 5.3% of FC flaps.
      Latissimus dorsi (40% of M group) and radial forearm free flaps (67% of FC group)
      were most commonly used in each group. There was a statistically significant
      difference between groups in rates of reoperation (M = 44% versus FC = 16%),
      postoperative infection (M = 38% versus FC = 12%), fracture nonunion (M = 40%
      versus FC = 21%), and donor site morbidity (M = 25% versus FC = 4%).
      Nonstatistically significant differences were encountered with higher rates of
      osteomyelitis (M = 14.6% versus FC = 10.5%), unplanned bone graft (M = 14.6
      versus FC = 10.5%), and inability to bear full weight at 1 year (M = 30.2% versus
      FC = 17.0%) found in the M group. In our cohort, M flaps used for metal coverage
      resulted in higher rates of reoperation, postoperative infections, and flap loss
      than FC flaps (M = 61% versus FC = 25%, p < 0.05). CONCLUSION: Statistically
      higher complication rates in key reliability markers were found in the M free
      flap group. This study found FC free flaps to be more reliable for reconstruction
      of lower limb injuries in a major trauma center.

PMID- 22588795
TI  - Changes in vascular anatomy following reconstructive surgery: an in vivo
      angiographic demonstration of the delay phenomenon and venous recanalization.
AB  - BACKGROUND: Although a surgical insult may substantially alter local vascular
      anatomy within tissues, studies that have clearly demonstrated these changes as
      being dynamic phenomena have not been widely reported. The current study aimed to
      explore the changes in abdominal wall vasculature after a surgical insult.
      METHODS: The arterial and venous anatomy of both the deep and superficial
      epigastric systems of the abdominal wall were explored with computed tomographic
      angiography (CTA) performed before and after bilateral removal of both bilateral
      deep and superficial inferior epigastric systems. RESULTS: Several unique
      anatomic findings were evident, with dilatation of both deep superior epigastric
      arteries and recanalization of the superficial inferior epigastric veins across
      the surgical scar, despite previous surgical division. CONCLUSION: The current
      study demonstrated that there are changes in both major and minor axial vessels
      and in both the arterial and venous systems after surgical insult. CTA may be of
      value in identifying these changes prior to surgery utilizing local vasculature.

PMID- 22588796
TI  - Simple clinical test to detect deltoid muscle dysfunction causing weakness of
      abduction--"akimbo" test.
AB  - INTRODUCTION: Full range of motion and powerful shoulder abduction can be
      performed without any deltoid muscle function by the supplemental action of the
      supraspinatus and biceps brachii muscles. For evaluation of deltoid muscle
      function, we need to negate these actions, which can be done with the "akimbo
      test," in which patients place their hands on the iliac crest with abduction in
      the coronal plane and internal rotation of the shoulder joint while
      simultaneously flexing the elbow joint and pronating the forearm. METHODS: We
      examined the akimbo test in five patients with incomplete upper-type brachial
      plexus injury, five patients with suprascapular nerve palsy, and six patients
      with axillary nerve palsy. Presence of some abduction is a prerequisite to
      perform this test. RESULTS: No patient with incomplete upper-type brachial plexus
      injury could demonstrate this sign when the deltoid did not show a certain level
      of the power to abduct the shoulder joint. All patients with suprascapular nerve
      could demonstrate this sign as the deltoid was normal. No patient with axillary
      nerve paralysis could demonstrate this sign. CONCLUSION: The akimbo test is a
      simple clinical test to determine deltoid muscle paralysis or dysfunction,
      especially when patients can demonstrate shoulder abduction due to supplementary
      action of other muscles.

PMID- 22588797
TI  - Harvest of an entire gracilis muscle and tendon for use in functional muscle
      transfer: a novel technique.
AB  - The use of the free functioning, innervated gracilis muscle has evolved to become
      an invaluable tool in the restoration of elbow flexion and prehension in patients
      undergoing reconstruction following brachial plexus injuries. Although there are
      many different methods of the gracilis muscle harvest, most if not all harvest
      methods begin proximally. The purpose of this article is to describe a novel
      distal harvest technique of the gracilis myocutaneous flap for brachial plexus
      patients requiring restoration of elbow or finger flexion. A harvest method
      commencing with a distal dissection either at the distal insertion of the
      gracilis at the pes anserine or at the distal medial thigh at the myotendinous
      junction will be described. The advantage of this novel method is to ensure that
      the entire gracilis muscle and its tendon are harvested to maximize the length of
      tendon that can be secured by a Pulvertaft weave into the biceps tendon or the
      finger flexors for elbow flexion and finger flexion respectively.

PMID- 22588798
TI  - The high-resolution ultrasonography and electrophysiological studies in nerve
      decompression for ulnar nerve entrapment at the elbow.
AB  - OBJECTIVE: To discuss a combination of high-resolution ultrasound and
      electrophysiological examination in diagnosis and evaluation of ulnar nerve
      entrapment at the elbow. METHOD: We retrospectively reviewed 20 healthy
      volunteers and 278 patients of ulnar nerve entrapment divided into three groups
      by McGowan grade, and we treated patients with subcutaneous or modified
      submuscular ulnar nerve transposition randomly. All the patients were followed
      for 2 years. The diagnosis and effects were confirmed by preoperative or
      postoperative cross-sectional area (CSA), motor conduction velocity (MCV),
      sensory conduction velocity, and nerve action potential (NAP). RESULTS: Healthy
      volunteers and grade I patients had significant differences in CSA, MCV, and NAP;
      grade I, II, and III patients had significant differences in CSA, MCV, and NAP;
      all patients had significant differences in CSA, MCV, and NAP before and after
      operations. CONCLUSION: High-resolution ultrasound and electrophysiological
      examination can be used in diagnosis and evaluation of operations of ulnar nerve
      entrapment at the elbow.

PMID- 22588799
TI  - Secret scar free gracilis flap.
AB  - The gracilis free flap is a workhorse in plastic surgery. We present a modified
      technique that relies on a single horizontal thigh-lift-type approach, which (1)
      gives wide pedicle exposure, (2) provides material for skin grafting, and (3)
      allows for distal flap transection without an additional incision. Eighteen
      gracilis free flaps were performed from 2007 to 2009 for lower extremity
      reconstruction. Complete flap survival was observed in 17 patients with one
      partial necrosis distally. Our approach allowed access to divide the distal
      gracilis tendon without a second incision in all cases. The mean scar length was
      16 +/- 3 cm and no hypertrophic scars were observed. In 15 patients, no visible
      scar was observed in the upright position, and in three patients, the scar was
      visible dorsally (2 +/- 1 cm). No sensory deficits were observed 6 months
      postoperatively. In addition, the split-thickness skin graft harvested from the
      skin paddle was sufficient to cover all defects.

PMID- 22588800
TI  - Female urethral reconstruction using a tubed rectus abdominis myocutaneous flap.
AB  - We describe the novel use of a rectus abdominis myocutaneous flap for
      reconstruction of the female urethra following an oncological pelvic resection.
      Reconstruction of the female urethra from the bladder neck to external urethral
      orifice was successfully performed, avoiding the need for a urostomy. To our
      knowledge, the myocutaneous flap has never been described for complete urethral
      reconstruction.

PMID- 22588801
TI  - Lithium storage in Li4Ti5O12 spinel: the full static picture from electron
      microscopy.
AB  - The full static picture of Li storage in Li(4)Ti(5)O(12) is derived using the
      latest spherical aberration-corrected scanning transmission electron microscopy
      and first-principles calculations. The accommodation of the additional Li(+) is
      directly visualized and the distribution of electrons introduced by lithium
      insertion deduced. Moreover, Li(4)Ti(5)O(12) is found to transform into
      Li(7)Ti(5)O(12) on lithiation by developing a dislocation-free coherent hetero
      interface.

PMID- 22588802
TI  - Development of pachytene FISH maps for six maize chromosomes and their
      integration with other maize maps for insights into genome structure variation.
AB  - Integrated cytogenetic pachytene fluorescence in situ hybridization (FISH) maps
      were developed for chromosomes 1, 3, 4, 5, 6, and 8 of maize using restriction
      fragment length polymorphism marker-selected Sorghum propinquum bacterial
      artificial chromosomes (BACs) for 19 core bin markers and 4 additional genetic
      framework loci. Using transgenomic BAC FISH mapping on maize chromosome addition
      lines of oats, we found that the relative locus position along the pachytene
      chromosome did not change as a function of total arm length, indicative of
      uniform axial contraction along the fibers during mid-prophase for tested loci on
      chromosomes 4 and 5. Additionally, we cytogenetically FISH mapped six loci from
      chromosome 9 onto their duplicated syntenic regions on chromosomes 1 and 6, which
      have varying amounts of sequence divergence, using sorghum BACs homologous to the
      chromosome 9 loci. We found that successful FISH mapping was possible even when
      the chromosome 9 selective marker had no counterpart in the syntenic block. In
      total, these 29 FISH-mapped loci were used to create the most extensive pachytene
      FISH maps to date for these six maize chromosomes. The FISH-mapped loci were then
      merged into one composite karyotype for direct comparative analysis with the
      recombination nodule-predicted cytogenetic, genetic linkage, and genomic physical
      maps using the relative marker positions of the loci on all the maps. Marker
      colinearity was observed between all pair-wise map comparisons, although marker
      distribution patterns varied widely in some cases. As expected, we found that the
      recombination nodule-based predictions most closely resembled the cytogenetic map
      positions overall. Cytogenetic and linkage map comparisons agreed with previous
      studies showing a decrease in marker spacing in the peri-centromeric
      heterochromatin region on the genetic linkage maps. In fact, there was a general
      trend with most loci mapping closer towards the telomere on the linkage maps than
      on the cytogenetic maps, regardless of chromosome number or maize inbred line
      source, with just some of the telomeric loci exempted. Finally and somewhat
      surprisingly, we observed considerable variation between the relative arm
      positions of loci when comparing our cytogenetic FISH map to the B73 genomic
      physical maps, even where comparisons were to a B73-derived cytogenetic map. This
      variation is more evident between different chromosome arms, but less so within a
      given arm, ruling out any type of inbred-line dependent global features of linear
      deoxyribonucleic acid compared with the meiotic fiber organization. This study
      provides a means for analyzing the maize genome structure by producing new
      connections for integrating the cytogenetic, linkage, and physical maps of maize.

PMID- 22588804
TI  - Variation in the composition of milk of Asian elephants (Elephas maximus)
      throughout lactation.
AB  - We investigated milk nutrient composition from three Asian elephant cows over the
      first 3 years of lactation, including two consecutive lactations in one cow. Body
      mass gain is presented for three calves during the first year. Milk samples (n =
      74) were analyzed for dry matter (DM), fat, crude protein (CP), sugar, ash,
      calcium (Ca), phosphorus (P), and potassium (K); gross energy (GE) was
      calculated. Concentrations of most nutrients changed over lactation: DM, fat, CP,
      Ca, P, and GE were positively correlated to calf age; sugar was negatively
      correlated to calf age. GE doubled between birth (1 kcal/g) and 2 years of age (2
      kcal/g). After accounting for calf age, GE, fat, Ca, and P concentrations
      differed among the cows. Milk composition also differed between two lactations
      from the same cow. When milk nutrients were expressed on a mg per kcal basis, the
      pattern changes: CP, Ca, and P remained relatively constant over lactation on a
      per energy basis. Calf mass quadrupled over the first year of life; mass gain was
      linear at 0.9 kg/day. Asian elephant milk composition is variable, both across
      lactations and between cows, complicating efforts to determine representative
      values for comparative studies and for the formulation of elephant milk formulas.
      The fact that CP, Ca, and P were all relatively constant when expressed on a per
      energy basis may be of biological significance. The increase in nutrient density
      over lactation undoubtedly limits maternal water loss, reducing the volume of
      milk necessary to support the calf.

PMID- 22588805
TI  - A novel control architecture for physiological tremor compensation in
      teleoperated systems.
AB  - BACKGROUND: Telesurgery delivers surgical care to a 'remote' patient by means of
      robotic manipulators. When accurate positioning of the surgeon's tool is
      required, as in microsurgery, physiological tremor causes unwanted imprecision
      during a surgical operation. Accurate estimation/compensation of physiological
      tremor in teleoperation systems has been shown to improve performance during
      telesurgery. METHOD: A new control architecture is proposed for estimation and
      compensation of physiological tremor in the presence of communication time
      delays. This control architecture guarantees stability with satisfactory
      transparency. In addition, the proposed method can be used for applications that
      require modifications in transmitted signals through communication channels.
      Stability of the bilateral tremor-compensated teleoperation is preserved by
      extending the bilateral teleoperation to the equivalent trilateral Dual
      master/Single-slave teleoperation. The bandlimited multiple Fourier linear
      combiner (BMFLC) algorithm is employed for real-time estimation of the operator's
      physiological tremor. RESULTS: Two kinds of stability analysis are employed. In
      the model-base controller, Llewellyn's Criterion is used to analyze the
      teleoperation absolute stability. In the second method, a nonmodel-based
      controller is proposed and the stability of the time-delayed teleoperated system
      is proved by employing a Lyapunov function. Experimental results are presented to
      validate the effectiveness of the new control architecture. The tremorous motion
      is measured by accelerometer to be compensated in real time. In addition, a
      Needle-Insertion setup is proposed as a slave robot for the application of
      brachytherapy, in which the needle penetrates in the desired position. The slave
      performs the desired task in two classes of environments (free motion of the
      slave and in the soft tissue). CONCLUSION: Experiments show that the proposed
      control architecture effectively compensates the user's tremorous motion and the
      slave follows only the master's voluntary motion in a stable manner.

PMID- 22588803
TI  - Ambient temperature and biomarkers of heart failure: a repeated measures
      analysis.
AB  - BACKGROUND: Extreme temperatures have been associated with hospitalization and
      death among individuals with heart failure, but few studies have explored the
      underlying mechanisms. OBJECTIVES: We hypothesized that outdoor temperature in
      the Boston, Massachusetts, area (1- to 4-day moving averages) would be associated
      with higher levels of biomarkers of inflammation and myocyte injury in a repeated
      measures study of individuals with stable heart failure. METHODS: We analyzed
      data from a completed clinical trial that randomized 100 patients to 12 weeks of
      tai chi classes or to time-matched education control. B-type natriuretic peptide
      (BNP), C-reactive protein (CRP), and tumor necrosis factor (TNF) were measured at
      baseline, 6 weeks, and 12 weeks. Endothelin-1 was measured at baseline and 12
      weeks. We used fixed effects models to evaluate associations with measures of
      temperature that were adjusted for time-varying covariates. RESULTS: Higher
      apparent temperature was associated with higher levels of BNP beginning with 2
      day moving averages and reached statistical significance for 3- and 4-day moving
      averages. CRP results followed a similar pattern but were delayed by 1 day. A 5
      degrees C change in 3- and 4-day moving averages of apparent temperature was
      associated with 11.3% [95% confidence interval (CI): 1.1, 22.5; p = 0.03) and
      11.4% (95% CI: 1.2, 22.5; p = 0.03) higher BNP. A 5 degrees C change in the 4-day
      moving average of apparent temperature was associated with 21.6% (95% CI: 2.5,
      44.2; p = 0.03) higher CRP. No clear associations with TNF or endothelin-1 were
      observed. CONCLUSIONS: Among patients undergoing treatment for heart failure, we
      observed positive associations between temperature and both BNP and CRP
      predictors of heart failure prognosis and severity.

PMID- 22588806
TI  - A dipeptide-based multicolored-switching luminescent solid material: when
      molecular assemblies meet mechanochemical reaction.
AB  - Color schemes: A mechanochromic material composed of two types of peptides
      bearing a pyrene group and rhodamine B moieties, respectively, displays
      multiluminescent colors, such as blue, green, and reddish in one sample (see
      picture). The mechanochromic behavior is based on a combined switching of
      molecular assemblies and chemical structure.

PMID- 22588807
TI  - Depleted Uranium. Is it potentially involved in the recent upsurge of
      malignancies in populations exposed to war dust?
AB  - Due to its extreme density, depleted Uranium (DU) has recently entered the
      warfare industry and became a major pollutant to the biosphere. Although DU is
      less radioactive than natural Uranium, it still retains all its chemical
      toxicity. Limited data exists regarding the long-term hazards of DU on humans,
      however, it is suspected to be a major toxic and mutagenic agent. Literature
      review reveals the scarcity of the World Health Organization's knowledge
      regarding related DU-malignancies. Battlefield reports documented a steady rise
      of malignancies and newborn malformations after war, that is, leukemia in the
      Balkans, and congenital anomalies and Kaposi  sarcoma (KS) in Iraq. Kaposi
      sarcoma in Iraq has a quite aggressive behavior compared with the classic KS
      before, suggesting a potential relation with DU, and possibly a different DU
      related KS-type. Children are more susceptible to radiation than adults. This
      enlarges the responsibility of the medical communities for an evidence-based
      attitude towards DU, and to ban its use until proven otherwise. We, as medical
      bodies have a human approach - stand with man not to be mistreated, and with
      green norms, which veto all suspected pollutants of the planet. Until further
      notice, DU should be thoroughly checked for safety,  before it kills.

PMID- 22588808
TI  - Association of cluster of differentiation 36 gene variant rs1761667 (G>A) with
      metabolic syndrome in Egyptian adults.
AB  - OBJECTIVE: To investigate the relationship between cluster of differentiation
      (CD)36 gene variant rs1761667 (G>A) and metabolic syndrome (MetS) and its
      components in Egyptian patients. METHODS: This case-control study was conducted
      on MetS patients attending Suez Canal University Hospital, Egypt from November
      2010 to October 2011. Peripheral blood was collected from 100 patients and 100
      healthy controls for DNA extraction. The single nucleotide polymorphism (SNP)
      CD36 gene rs1761667 (G>A) was genotyped using real-time polymerase chain
      reaction, and allele discrimination technique. RESULTS: Distribution of CD36
      genotypes in the patient group was AA (n=25), AG (n=70), and GG (n=5) while in
      the control group it was AA (n=51), AG (n=48), and GG (n=1). Both AG and GG
      genotypes were significantly more prevalent among MetS patients (p<0.001). The
      odds ratio (OR) for the high risk allele (G) is 2 with 95% confidence interval
      from 1.30-3.07 (p<0.001). Patients with genotypes AG and GG had significantly
      higher systolic blood pressure, wider waist circumstance, and higher degree of
      dyslipidemia (p<0.001) than patients with genotype AA. CONCLUSION: Our findings
      show that CD36 rs1761667 SNP is positively associated with increased risk of MetS
      and its components with genotype AG heterozygotes showing highest frequency among
      MetS patients.

PMID- 22588809
TI  - Serum resistin levels in patients with type 2 diabetes mellitus and its
      relationship with body composition.
AB  - OBJECTIVE: To assess the relationships of resistin concentrations with body mass
      index (BMI), body fat mass, lean body mass, and body protein mass in patients
      with type 2 diabetes mellitus (DM). METHODS: This cross-sectional study was
      conducted in the Department of Physiology, College of Medicine,  King Saud
      University, Riyadh, Kingdom of Saudi Arabia from April 2008 to March 2011. A
      total of 229 subjects were selected for the study. Body composition was assessed
      by bioelectrical impedance analyzer. Parameters recorded included BMI, waist hip
      ratio (WHR), total body water, fat, protein, and lean body masses. Blood samples
      were analyzed for glucose, glycosylated hemoglobin (HbA1c), and resistin levels.
      RESULTS: We found that BMI, WHR, fasting blood glucose, HbA1c, and resistin
      levels were significantly higher in diabetics compared to non-diabetic healthy
      individuals. Fat mass was significantly higher in diabetic patients compared with
      controls, while the difference for muscle mass and lean body mass was non
      significant. A significant positive correlation was observed between plasma
      levels of resistin and fat mass in patients with DM (r=0.2824, p=0.0030).
      CONCLUSION: Type 2 DM patients have significantly higher resistin levels that are
      positively correlated with body fat mass supporting the evidence that resistin
      plays an important role in the pathogenesis of obesity and insulin resistance.

PMID- 22588810
TI  - Intestinal motility in acute uremia and effects of erythropoietin.
AB  - OBJECTIVE: To investigate intestinal motility changes due to uremia, and the
      effect of pretreatment with erythropoietin. METHODS: This randomized control
      study was conducted in the Department of Physiology, Faculty of Medicine,  Ain
      Shams University, Cairo, Egypt from September 2010 to July 2011. Forty adult
      female Wistar albino rats were allocated into 3 groups: control group, gentamicin
      treated group, receiving intraperitoneal gentamicin sulphate (100 mg/kg for 5
      days), and erythropoietin-gentamicin-treated group, receiving subcutaneous
      erythropoietin (1000 IU/kg for 3 days) prior to gentamicin injection. Isolated
      segments of duodenum and descending colon was subjected to in vitro motility
      study. Plasma creatinine and urea were assayed. RESULTS: Induction of acute renal
      failure by gentamicin treatment resulted in a significant decrease in frequency
      of contraction of the duodenum and descending colon, an increase in the average
      duration of contraction of the duodenum, and a significant decrease in the
      average force of contraction in the descending colon. Moreover, the average force
      of contraction in response to acetylcholine was significantly decreased in the
      duodenum. The erythropoietin-gentamicin-treated group revealed a significant
      decrease in plasma creatinine and urea, and a significant increase in the
      duodenal average force of contraction and motility index, and colonic frequency.
      The duodenal absolute and average forces of contraction after acetylcholine
      increased significantly. CONCLUSION: Acute uremia impairs small and large
      intestinal motility, probably due to uremic toxins and autonomic dysfunction.
      Erythropoietin pretreatment protected against intestinal dysmotility through the
      improvement of renal function and its neurotropic action.

PMID- 22588811
TI  - The mechanism of lipid raft mediating chemoresistance of cervical cancer.
AB  - OBJECTIVE: To investigate the mechanism of lipid raft mediating chemotherapy
      resistance in cervical cancer. METHODS: This experiment was carried out in the
      Tongji Medical College, Huazhong University of Science and Technology, Wuhan,
      China from June 2010 to February 2011. Hela cells were divided into 6 groups:
      control group (Ctrl), cisplatin group (Cis), lipid raft interference agent group
      (MCD), NADPH oxidase inhibitor group (Apo), lipid raft interference agent
      combined with cisplatin group (MCD+Cis), and NADPH oxidase inhibitor combined
      with cisplatin group (Apo+Cis). After the cervical cancer cells were treated with
      a correspondent agent for 24 hours, the number of surviving cells were measured
      utilizing cell counting kits-8 (CCK-8), and the hypoxia inducible factor-1alpha
      (HIF-1alpha) levels were detected by Western blotting. Reactive oxygen species
      (ROS) levels were measured indirectly by detection of dichlorodihydrofluorescein
      fluorescence activity. RESULTS: The cell growth of MCD slowed down (survival
      cells was 62% compared with the Ctrl group), with the Apo group showing a similar
      effect (65% in the control group), and 49% for the Cis group, MCD+Cis was 21%,
      and Apo+Cis was 23%. While the level of HIF-1alpha protein and ROS of the MCD
      group, Apo group, Cis group, MCD+Cis group and Apo+Cis group were decreased
      significantly compared to the control group. The level of HIF-1alpha of MCD group
      decreased by 69.9%, Apo group by 60.2%, Cis group was 55.5%, MCD+Cis group by
      21.1% and Apo+Cis group by 25.4%, while the level of ROS also decreased in the
      MCD group by 38.6%, Apo group by 35.3%, Cis group by 24%, MCD+Cis group by 12.3%
      and Apo+Cis group by 12.8%. CONCLUSION: Lipid raft may up-regulate ROS level and
      HIF-1alpha expression through activating NADPH oxidase, and thus promote
      chemotherapy resistance in cervical cancer.

PMID- 22588812
TI  - Effects of strontium ranelate on cortical bone collagen integrity.
AB  - OBJECTIVE: To investigate the effect of strontium ranelate on bone collagen cross
      linking in an ovariectomized rat model. METHODS: Twenty-eight adult (12 weeks)
      albino female Wistar rats weighing between 200-250 g (n=7 per group) were divided
      into sham-operated, ovariectomized, prevention, and treatment groups. Animals in
      the prevention group were treated with strontium ranelate (500 mg/kg/day orally)
      for 120 days, starting immediately after ovariectomy. Animals in the treatment
      group were treated with strontium ranelate (500 mg/kg/day orally) for 120 days,
      starting 90 days after ovariectomy. At the end of the experimental period,
      stress, strain, and toughness of the cortical femur was measured, and collagen
      ultrastructure was evaluated. The study was conducted in Mersin University
      Biophysics Laboratory, Mersin University, Mersin, Turkey from January to May
      2008. RESULTS: Stress, strain, and toughness values decreased in ovariectomized,
      prevention, and treatment groups when compared with the sham-operated group. In
      this study, fiber organization was observed in the sham-operated group, whereas
      the parallel packing of fibrils was completely replaced by a random arrangement
      in the ovariectomized, prevention, and treatment groups. CONCLUSION: Strontium
      ranelate treatment did not repair collagen cross-linking in ovariectomized rats.

PMID- 22588813
TI  - Vitamin D deficiency in rheumatoid arthritis. Prevalence and association with
      disease activity in Western Saudi Arabia.
AB  - OBJECTIVE: To estimate the prevalence of low serum vitamin D level (25[OH]D) in
      patients with rheumatoid arthritis (RA) compared with healthy controls, and to
      analyze the association between 25(OH)D and disease activity. METHODS: This
      retrospective analysis included 100 RA patients (85% women) and 100 controls, not
      on vitamin D supplements from January 2010 to December 2011 at a tertiary care
      center at the Department of Internal Medicine, King Abdulaziz University Hospital
      (KAUH), Jeddah, Kingdom of Saudi Arabia. Disease activity was measured using the
      disease activity score index (DAS28). According to the DAS28 score, RA patients
      were divided into 3 groups as high, moderate, and low disease activity. Patients'
      serum 25(OH)D was measured in a centralized laboratory. RESULTS: The mean 25(OH)D
      in patients with RA was similar to the control group (32.3+/-14.4 nmol/L) versus
      (31.4+/-16.4 nmol/L) (p=0.41). Patients with high disease activity had the lowest
      25(OH)D levels (18.25+/-8.3 nmol/L) compared with patients with moderate (35.13+/
      15.2 nmol/L) and low (38.05+/-7.3 nmol/L) disease activity (p<0.001). Serum
      25(OH)D was negatively correlated with DAS28, which was statistically significant
      (r= -0.42, p<0.0001). CONCLUSION: Serum vitamin D levels in RA patients were
      similar to the healthy control group. However, significantly lower 25(OH)D values
      were found in patients who are poorly responding to treatment, and not in a state
      of disease remission.

PMID- 22588814
TI  - Needle acupuncture for osteoarthritis of the knee. A systematic review and
      updated meta-analysis.
AB  - OBJECTIVE: To evaluate the efficacy of treatment with acupuncture for knee
      osteoarthritis. METHODS: We searched PUBMED, EMBASE, and the Cochrane Central
      Register of Controlled Trials databases from July to October 2011 for randomized
      controlled trials that compared needle acupuncture with sham acupuncture,
      standard care, or waiting list control groups in patients with knee
      osteoarthritis. Of the 490 potentially relevant articles, 14 RCTs involving 3,835
      patients were included in the meta-analysis. Two authors independently extracted
      outcome data on short-term and long-term pain and functional measures. RESULTS:
      Standardized mean differences and 95% confidence intervals were calculated using
      the mean differences in improvements from baseline and the associated standard
      deviations in patients assigned to acupuncture and those assigned to control
      groups according to measurement time points. Compared with sham acupuncture
      control treatment, acupuncture was significantly better at relieving pain
      (p=0.002) and restoring function (p=0.01) in the short-term period, and relieving
      pain (p=0.06) and restoring function (p=0.06) in the long-term. Compared with the
      standard care and waiting list control treatments, acupuncture was significantly
      better at relieving pain and restoring function. CONCLUSION: Acupuncture provided
      significantly better relief from knee osteoarthritis pain and a larger
      improvement in function than sham acupuncture, standard care treatment, or
      waiting for further treatment.

PMID- 22588815
TI  - The influence of gender and place of residence on cardiovascular diseases and
      their risk factors. The Isfahan cohort study.
AB  - OBJECTIVE: To determine the impact of gender and place of residence on
      cardiovascular disease (CVD) events and related risk factors. METHODS: In a
      prospective cohort study, 6323 participants free of CVD (3255 women), with age of
      more than 35 years from 3 cities (Isfahan, Najafabad, and Arak) and their rural
      districts in central Iran were followed-up from 2001 to 2007. This study was
      carried out at the Cardiovascular Research Institute of Isfahan University of
      Medical Sciences, Isfahan, Iran. Endpoints were defined as fatal- and nonfatal 
      myocardial infarction, sudden cardiac death, unstable angina and stroke that
      constituted CVD events. RESULTS: Subjects in the rural area had significantly
      better risk factor profile in terms of most CVD risk factors in both genders, but
      it was reverse for low density lipoprotein (LDL)-cholesterol in both genders, and
      smoking in men. Except for smoking, men had an overall better risk factor profile
      compared to women. The age and risk factors adjusted hazard ratio of living in
      rural area was 0.71 (95% confidence interval [CI]: 0.51-0.99) for men, and 0.63
      (95% CI: 0.44-0.91) for women. The age of CVD occurrence was similar in men and
      women, and in rural and urban areas. Hypertension was the strongest predictor of
      these events except for rural men showing that high LDL-cholesterol was the
      strongest risk factor. CONCLUSION: The findings in this study documented
      differences in CVD risk factors affecting the occurrence of CVD events according
      to gender and place of residence. Such differences should be taken into account
      in future preventive public health strategies for CVD prevention.

PMID- 22588816
TI  - Prevalence of celiac disease in children with type 1 diabetes mellitus screened
      by anti-tissue transglutaminase antibody from Western Saudi Arabia.
AB  - OBJECTIVE: To determine the prevalence of celiac disease (CD) in children and
      adolescents with type 1 diabetes mellitus (T1DM) using anti-tissue
      transglutaminase (anti-tTG) antibodies. METHODS: A retrospective hospital record
      based study of all children and adolescents with T1DM who were screened for CD
      was conducted at the Pediatric Diabetes Clinic of King Abdulaziz University
      Hospital, Jeddah, Kingdom of Saudi Arabia (KSA) between October 2002 and June
      2011. RESULTS: A total of 430 children with T1DM were screened by anti-tTG
      antibody. The median age at screening was 10.7 years (range; 1.1-18). The study
      cohort included 232 (54%) Saudi patients, and females constituted 58.8% of the
      total number. Anti-tTG antibody screening was positive in 91 (21.2%) patients.
      Forty-eight (11.2%) out of 430 children screened had biopsy-proven CD. Forty-two
      patients with CD (87.5%) were asymptomatic. Patients with CD had less weight for
      age (p=0.007), and height for age (p=0.03) z-scores than non-CD patients. They
      showed more association with anemia (p<0.001), low albumin level (p<0.001), and
      autoimmune thyroid disease (p=0.002). There was no difference in the mean
      glycosylated hemoglobin level (p=0.38), or insulin requirements (p=0.74) between
      the 2 groups. CONCLUSION: The prevalence of CD in patients with T1DM from the
      Western region of KSA is considered among the highest reported. Therefore,
      routine screening through proper serological testing is recommended.

PMID- 22588817
TI  - Men's knowledge and attitude towards breast cancer in Saudi Arabia. A cross
      sectional study.
AB  - OBJECTIVE: To identify men's knowledge and attitude towards early detection of
      breast cancer. METHODS: This cross-sectional study was conducted at the
      outpatient clinics of King Abdulaziz University Hospital, Jeddah, Kingdom of
      Saudi Arabia. Five hundred and fifty participants were selected by systemic
      randomization. The distributed questionnaire included: demographics,  knowledge
      and its source on breast cancer, beliefs and practice regarding breast self
      examination (BSE), mammography, and difficulties that may prevent women from
      seeking medical help. The questionnaire was filled anonymously and in private.
      RESULTS: The response rate was 90.9%, and most were employees (63.2%). Physicians
      represented 43.4% of the source of knowledge, followed by the internet (40.4%),
      and last, the media (30.4%). Breast mass was the most common symptom (36.6%),
      followed by change of breast size (26%) and pain (20.2%), while 24% did not know
      the symptoms of breast cancer. Approximately 13% believed that all cases of
      breast cancer ended with mastectomy. Only 57.6% were aware of the importance of
      BSE in early detection of breast cancer, and approximately 90% did not know the
      importance of mammography. CONCLUSION: Awareness campaigns aimed at husbands and
      men in general are to be strongly considered. They should encourage their wives
      and families to enroll in awareness and screening campaigns.

PMID- 22588818
TI  - Experience and attitude of interns to pelvic and sensitive area examinations
      during their undergraduate medical course.
AB  - OBJECTIVE: To explore the experience of interns in sensitive area examination
      during their undergraduate medical course and identify factors interfering with
      such examinations. METHODS: A cross sectional study was carried out from May to
      June 2010. Interns (n=315) at King Saud University College of Medicine were
      invited via email to complete a web-based questionnaire developed using
      surveymonkey.com. RESULTS: Out of 315 interns, 211 completed the questionnaire;
      60% males and 40% females. The mean percentage of interns who never performed any
      of these examinations was 28.9% for digital rectal examination, 17.5% for breast,
      43.1% for female pelvic examination, 13.3% for inguinal (hernia), and 34.6% for
      male external genitalia. Compared to females, male students conducted more rectal
      examinations (87 versus 63, p<0.005), and male external genitalia examinations
      (112 versus 26, p<0.001). On the other hand, compared to male students, females
      conducted more pelvic examination (68 versus 52, p=0.03) and breast examinations
      (92 versus 82, p=0.27). The most common reasons for not performing sensitive area
      examinations included patient's refusal (33.1%), and examining patients of
      opposite gender (27.6%). Confidence in performance of these examinations was
      correlated to increased frequency of the examination. CONCLUSION: This study
      highlights that most common factors interfering with the students' conducting
      sensitive area examinations are patient's refusal and examining patients of the
      opposite sex. There is a strong correlation between increased frequency of
      conducting an examination and student's confidence in performance.

PMID- 22588819
TI  - Barriers to feedback in undergraduate medical education. Male students'
      perspective in Central Saudi Arabia.
AB  - OBJECTIVE: To explore the views of undergraduate medical students regarding the
      presence and sources of barriers to effective feedback in their setting. METHODS:
      This cross-sectional study was conducted at the College of Medicine, Department
      of Medical Education, King Saud bin Abdul-Aziz University for Health Sciences,
      Riyadh, Kingdom of Saudi  Arabia from April to June 2010. A self-administered
      questionnaire was used to explore the objectives of the study. RESULTS: One
      hundred and eighty-six male undergraduate medical students participated in this
      study. Approximately 45% indicated presence of barriers to effective feedback.
      These include: absence of a clear system of feedback; inadequate skills of
      teachers for provision-effective feedback; and to a lesser extent, students' fear
      of insult due to feedback. Most participants showed their interest and readiness
      to receive more professional feedback in the future. CONCLUSION: This study has
      showed the presence of barriers as perceived by medical students, which could
      significantly minimize utilization of feedback in medical education. The reported
      barriers should be addressed to utilize the vital role of feedback in the
      learning process of undergraduate medical students.

PMID- 22588820
TI  - Cowden syndrome. Early presentation, late diagnosis.
AB  - Cowden syndrome is a rare genodermatosis characterized by the formation of
      hamartomas in various organs and increased risk of malignancy. This disease has
      variable expression and often presents with subtle skin signs, which can be
      missed. We report a 39-year-old Saudi male who presented with acral keratoses of
      Cowden syndrome, and misdiagnosed and treated by many dermatologists as viral
      wart. We aim to increase awareness of Cowden syndrome among health care workers.

PMID- 22588821
TI  - Antibiotic sensitivity pattern of common community-acquired uropathogens in
      children in a Saudi tertiary care hospital.

PMID- 22588822
TI  - Digital rectal examination in the detection of prostate cancer. Perception of
      training received and competence amongst house officers in a resource challenged
      setting.

PMID- 22588823
TI  - Meningitis and encephalitis in infants and children.

PMID- 22588824
TI  - Expanding the horizon of the thymine isostere biochemistry: unique cyclobutane
      dimers formed by photoreaction between a thymine and a toluene residue in the
      dinucleotide framework.
AB  - Substituted toluenyl groups are considered as close isosteres of the thymine
      residue. They can be recognized by DNA polymerases as if they were thymine. These
      toluene derivatives are generally inert toward radical additions, including the
      [2+2] photo-cycloadditions, due to the stable structure of the aromatic ring and
      are usually used as solvents for radical reactions. Surprisingly, after
      incorporating toluene into the dinucleotide framework, we found that the UV
      excited thymine residue readily dimerizes with the toluenyl moiety through a
      [2+2] photo-addition reaction. Furthermore, the reaction site on the toluenyl
      moiety is not the C5=C6 bond, as commonly observed in cyclobutane pyrimidine
      dimers, but the C4=C5 or C3=C4 instead. Such a reaction pattern suggests that in
      the stacked structure, it is one of these bonds, not the C5=C6, that is close to
      the thymine C5=C6 bond. A similar structural feature is found in DNA duplex with
      a thymine replaced by a 2,4-difluorotoluene. Our results argue that although the
      substituted toluenyl moieties closely mimic the size and shape of the thymine
      residue, their more hydrophobic nature determines that they stack on DNA bases
      differently from the natural thymine residue and likely cause local
      conformational changes in duplex DNA.

PMID- 22588825
TI  - Quality of care in systemic lupus erythematosus: application of quality measures
      to understand gaps in care.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) affects 1 in 2500 Americans and is
      associated with significant morbidity and mortality. The recent development of
      SLE quality measures provides an opportunity to understand gaps in clinical care
      and to identify modifiable factors associated with variations in quality.
      OBJECTIVE: To evaluate performance on SLE quality measures as well as differences
      in quality of care by demographic, socioeconomic, disease, and health system
      characteristics. DESIGN AND PATIENTS: Cross-sectional analysis of data derived
      from the Lupus Outcomes Study, a prospective, longitudinal study of 814
      individuals. Principal data collection was through annual structured telephone
      surveys between 2009-2010. Data on 13 SLE quality measures was collected. We used
      regression models to estimate demographic, socioeconomic, disease, and health
      system characteristics associated with performance on individual and overall
      quality measures. OUTCOME MEASURES: Performance on each quality measure and
      overall performance on all measures for which participants were eligible (pass
      rate). RESULTS: Participants were eligible for a mean of five measures (range 2
      12). Performance varied from 29 % (assessment of cardiovascular risk factors) to
      90 % (sun avoidance counseling). The overall pass rate was 65 % (95 % CI 64 %, 65
      %). In unadjusted analyses, younger age, minority race/ethnicity, poverty,
      shorter disease duration, fewer physician visits, and lack of health insurance,
      were associated with lower pass rates. Receiving care in public sector managed
      care organizations was associated with higher pass rates. After adjustment,
      younger age, having fewer physician visits and lacking health insurance remained
      significantly associated with lower performance; receiving care in public sector
      managed care organizations remained associated with higher performance.
      CONCLUSIONS: We identified a number of gaps in clinical care for SLE. Factors
      associated with the health care system, including presence and type of health
      insurance, were the primary determinants of performance on quality measures in
      SLE.

PMID- 22588826
TI  - Time to recognize our fellow travellers.
AB  - It is increasingly apparent that human health is reliant on our fellow
      travellers, the innumerable microorganisms that inhabit our bodies. This
      realization has led to the concept of the superorganism, which suggests that
      shared metabolic and signalling pathways are crucial for optimal existence of
      both host and commensal microflora. This commentary focuses on implications of
      this paradigm for personalized medicine and therapeutics. Study of the
      microbiome, the collection of microorganisms inhabiting the body, may identify
      disease-associated microbial profiles with pathophysiological and diagnostic
      value. As with genomics, companies will emerge offering direct to consumer
      microbiome analysis. Probiotics can potentially modulate the superorganism for
      therapeutic benefit. However, the probiotics industry will need to undergo a
      transformation, with increased focus on stringent manufacturing guidelines and
      high-quality clinical trials. Ultimately, we suggest that healthcare will move
      beyond its prevailing focus on human physiology, and embrace the superorganism as
      a paradigm to understand disease.

PMID- 22588828
TI  - Isolated corneal pseudodendrites as the initial manifestation of tyrosinemia type
      II in monozygotic twins.
AB  - Fifteen-month-old twins presented with photophobia and bilateral corneal
      pseudodendrites, and tyrosinemia type II was suspected. Plasma tyrosine levels
      were elevated. After therapy with tyrosine-restricted diet, corneal lesions
      resolved. Bilateral pseudodendritic keratitis may be the initial or only
      manifestation of tyrosinemia type II.

PMID- 22588830
TI  - Synthesis of eight-membered lactones: intermolecular [6+2] cyclization of
      amphoteric molecules with siloxy alkynes.

PMID- 22588827
TI  - Predictors of inadequate prenatal care in methamphetamine-using mothers in New
      Zealand and the United States.
AB  - This study compared patterns of prenatal care among mothers who used
      methamphetamine (MA) during pregnancy and non-using mothers in the US and New
      Zealand (NZ), and evaluated associations among maternal drug use, child
      protective services (CPS) referral, and inadequate prenatal care in both
      countries. The sample consisted of 182 mothers in the MA-Exposed and 196 in the
      Comparison groups in the US, and 107 mothers in the MA-Exposed and 112 in the
      Comparison groups in NZ. Positive toxicology results and/or maternal report of MA
      use during pregnancy were used to identify MA use. Information about
      sociodemographics, prenatal care and prenatal substance use was collected by
      maternal interview. MA-use during pregnancy is associated with lower
      socioeconomic status, single marital status, and CPS referral in both NZ and the
      US. Compared to their non-using counterparts, MA-using mothers in the US had
      significantly higher rates of inadequate prenatal care. No association was found
      between inadequate care and MA-use in NZ. In the US, inadequate prenatal care was
      associated with CPS referral, but not in NZ. Referral to CPS for drug use only
      composed 40 % of all referrals in the US, but only 15 % of referrals in NZ. In
      our study population, prenatal MA-use and CPS referral eclipse maternal
      sociodemographics in explanatory power for inadequate prenatal care. The
      predominant effect of CPS referral in the US is especially interesting, and
      should encourage further research on whether the US policy of mandatory reporting
      discourages drug-using mothers from seeking antenatal care.

PMID- 22588831
TI  - Extensive fibrosis caused by Pleural Tuberculosis: a lesson from a case without
      post-exposure-prophylaxis.
AB  - We report the case of a 9-year-old boy with extensive pleural fibrosis and
      contraction of the affected hemithorax secondary to pleural tuberculosis (TB),
      who was successfully treated with a 6 months course of the standard WHO regimen.
      Although well described for the adult population, this complication is rare among
      children and to our knowledge, no such case has been described since the
      widespread introduction of antitubercular therapy in the 1950s. This case
      underscores the importance of appropriate follow-up and administration of
      chemoprophylaxis after TB exposure.

PMID- 22588832
TI  - a membrane device for substrate-free photovoltaic characterization of quantum dot
      based p-i-n solar cells.

PMID- 22588833
TI  - Phenotyping studies to assess the effects of phytopharmaceuticals on in vivo
      activity of main human cytochrome p450 enzymes.
AB  - The extensive use of herbal drugs and their multiple components and modes of
      action suggests that they may also cause drug interactions by changing the
      activity of human cytochrome P450 enzymes. The purpose of the present review is
      to present the available data for the top 14 herbal drug sales in the U. S.
      Studies describing the effects of herbal drugs on phenotyping substrates for
      individual CYPs were identified by a comprehensive MEDLINE search. Drugs included
      Allium sativum (Liliaceae), Echinacea purpurea (Asteraceae), Serenoa repens
      (Arecaceae), Ginkgo biloba (Ginkgoaceae), Vaccinium macrocarpon (Ericaceae),
      Glycine max (Fabaceae), Panax ginseng (Araliaceae), Actea racemosa
      (Ranunculaceae), Hypericum perforatum (Hypericaceae), Silybum marianum
      (Asteraceae), Camellia sinensis (Theaceae), Valeriana officinalis
      (Valerianaceae), Piper methysticum (Piperaceae), and Hydrastis canadensis
      (Ranunculaceae) preparations. We identified 70 clinical studies in 69
      publications. The majority of the herbal drugs appeared to have no clear effects
      on most of the CYPs examined. If there was an effect, there was mild inhibition
      in almost all cases, as seen with garlic or kava effects on CYP2E1 and with
      soybean components on CYP1A2. The most pronounced effects were induction of CYP3A
      and other CYPs by St. John's wort and the inhibitory effect of goldenseal on
      CYP3A and CYP2D6, both being borderline between mild and moderate in magnitude.
      With the exceptions of St.John's wort and goldenseal, the information currently
      available suggests that concomitant intake of the herbal drugs addressed here is
      not a major risk for drugs that are metabolized by CYPs.

PMID- 22588834
TI  - Effects of rutin on the expression of PPARgamma in skeletal muscles of db/db
      mice.
AB  - The effect of rutin (RT) on the expression of PPARgamma in the skeletal muscle of
      db/db mice has been investigated. Thirty db/db mice were randomized into 5 equal
      groups: model control group (MCG), positive control group 30 mg/kg pioglitazone
      hydrochloride (PCG), low-dose rutin group 50 mg/kg (LRT), middle-dose rutin group
      100 mg/kg (MRT), high-dose rutin group 200 mg/kg (HRT), and 6 other db/m mice
      were used as the normal control (NC). The expression of PPARgamma mRNA and
      protein in the skeletal muscle was determined by real-time quantitative PCR and
      Western Blot, respectively. Treatment with HRT resulted in significant decreases
      in the plasma levels of glucose and lipids (p < 0.001). Compared to the MCG, the
      expression of PPARgamma mRNA and protein of the skeletal muscle was significantly
      increased in the HRT and PCG groups (p < 0.001 and p < 0.05, respectively). Rutin
      can increase the expression of PPARgamma in skeletal muscles of db/db mice.

PMID- 22588835
TI  - High molecular weight constituents of cranberry interfere with influenza virus
      neuraminidase activity in vitro.
AB  - Cranberry juice contains high molecular weight non-dialyzable material (NDM)
      which was found to inhibit hemagglutination induced by the influenza virus (IV)
      as well as to neutralize the cytotoxicity of IV in cell cultures. Because
      influenza virus surface glycoproteins hemagglutinin (HA) and neuraminidase (NA)
      are involved in viral replication and in the infectious process, we sought in the
      present study to examine the effect of NDM on neuraminidases which are the target
      of most anti-influenza drugs today. NDM inhibited the NA enzymatic activity of
      influenza A and B strains as well as that of Streptococcus pneumoniae. This
      finding is of importance considering the emergence of influenza isolates
      resistant to antiviral drugs, reaching 90 % in some places. The anti-NA activity
      of NDM, evaluated by the MUNANA method and expressed as the concentration
      required for 50 % inhibition (IC50), was most potent against N1 (IC50, 192
      ug/mL), less active against BN and N2 (IC50, 509 ug/mL and 1128 ug/mL,
      respectively), and moderately active against Streptococcus pneumoniae NA (IC50,
      594 ug/mL). The in vitro findings of the present study suggest that cranberry
      constituents may have a therapeutic potential against both A and B influenza
      virus infections and might also interfere with the development of secondary
      bacterial complications.

PMID- 22588836
TI  - Tanshinone IIA prevents uric acid nephropathy in rats through NF-kappaB
      inhibition.
AB  - The purpose of this research is to investigate the effect of tanshinone IIA, an
      extract of the Chinese medicine Que Xie Hua Yu Tang, on uric acid nephropathy
      (UAN) and to elucidate the underlying mechanisms. UAN rat model was established.
      Fifty UAN rats were randomly allocated into 5 groups: adenine-treated group,
      allopurinol-treated group, and low/middle/high dose of tanshinone IIA-treated
      groups. Meanwhile, another 10 rats were used as normal controls. Serum uric acid
      (UA), blood urea nitrogen (BUN), serum creatinine (Scr), MCP-1, and IL-1beta
      levels were measured. Histological staining was performed. Comparison between the
      adenine group and treatment (allopurinol and tanshinone IIA) groups showed
      compound treatment could attenuate the inflammation status of the kidneys and
      decrease serum UA levels. Among different kinds of medicine, tanshinone IIA had
      similar effects as allopurinol and exerted anti-inflammatory and renal protective
      effect in a dose-dependent manner. Furthermore, we found tanshinone IIA alone
      could also inhibit urate-induced MCP-1 and IL-1beta overexpression both in vivo
      and in vitro, accompanied with inhibition of NF-kappaB translocation from
      cytosome to nucleus. Tanshinone IIA could protect rats from uric acid-induced
      kidney damage, probably by attenuating renal inflammatory status.

PMID- 22588837
TI  - Inhibition of lysenin-induced hemolysis by all-E-lutein derived from the plant
      Dalbergia latifolia.
AB  - Lysenin is a pore-forming toxin derived from coelomic fluid of the earthworm
      Eisenia foetida. The model of lysenin-induced hemolysis includes the specific
      binding of lysenin to sphingomyelin, oligomerization of the pore proteins, and
      pore formation. Although the mechanism of lysenin-induced hemolysis is unique,
      its precise mechanism of action and its inhibitors are poorly understood. In the
      present study, we screened for inhibitors of lysenin-induced hemolysis by using
      an optimized screening system and found a methanolic extract of Dalbergia
      latifolia leaves to be a potential candidate. After isolation and identification,
      all-E-lutein was identified as the hemolysis inhibitor with an effective dose of
      0.025-2.5 ng/mL without any toxicity. The inhibition by all-E-lutein is likely to
      occur during the receptor binding and/or pore-forming protein oligomerization.

PMID- 22588838
TI  - The apoptosis pathway and the genetic predisposition to Achilles tendinopathy.
AB  - Achilles tendinopathy (AT) is a degenerative condition for which several risk
      factors have been implicated including components of the inflammatory pathway.
      The aim was to assess functional variants within genes encoding components of the
      apoptosis signaling cascade and the effectiveness of a polygenic apoptosis
      profile to capture tendinopathy (TEN) risk. A total of 358 unaffected control
      (CON) participants [159 South Africa (SA CON) and 199 Australia (AUS CON)] and
      166 affected AT (TEN) participants (87 SA TEN and 79 AUS TEN) were genotyped for
      four variants [CASP8 (rs384129), CASP8 (rs1045485), NOS3 (rs1799983), and NOS2
      (rs2779249)]. Logistic regression was used to derive risk models for AT. A
      receiver operator characteristic (ROC) curve was plotted to determine the
      effectiveness of a model to capture AT risk. This study indicates the independent
      association of CASP8_rs1045485 and CASP8_rs3834129 as well as their haplotype
      with AT risk and the identification of an optimal model which included genetic
      loci CASP8_rs384129 and CASP8_rs1045485 together with sex to capture AT risk in
      both SA and AUS. Collectively, these results further implicate the apoptosis
      signaling cascade as one of the biological pathways involved in the development
      of AT.

PMID- 22588839
TI  - Lamotrigine triggers the contact phase of coagulation.

PMID- 22588840
TI  - Discovery of small-molecule interleukin-2 inhibitors from a DNA-encoded chemical
      library.
AB  - Libraries of chemical compounds individually coupled to encoding DNA tags (DNA
      encoded chemical libraries) hold promise to facilitate exceptionally efficient
      ligand discovery. We constructed a high-quality DNA-encoded chemical library
      comprising 30,000 drug-like compounds; this was screened in 170 different
      affinity capture experiments. High-throughput sequencing allowed the evaluation
      of 120 million DNA codes for a systematic analysis of selection strategies and
      statistically robust identification of binding molecules. Selections performed
      against the tumor-associated antigen carbonic anhydrase IX (CA IX) and the pro
      inflammatory cytokine interleukin-2 (IL-2) yielded potent inhibitors with
      exquisite target specificity. The binding mode of the revealed pharmacophore
      against IL-2 was confirmed by molecular docking. Our findings suggest that DNA
      encoded chemical libraries allow the facile identification of drug-like ligands
      principally to any protein of choice, including molecules capable of disrupting
      high-affinity protein-protein interactions.

PMID- 22588841
TI  - Studies on the cardioprotective role of gallic acid against AGE-induced cell
      proliferation and oxidative stress in H9C2 (2-1) cells.
AB  - Epidemiological studies have shown that high glucose levels and oxidative stress
      cause elevation of advanced glycation end products (AGEs) that are known to
      contribute to diabetic complications. Thus, agents that hamper reactive oxygen
      species (ROS) load can be used as a potential drug against AGEs-mediated
      complications. Hence, the present study investigated the protective role of
      gallic acid (GA) against the effects of AGEs in cardiac H9C2(2-1) cells. Exposure
      of cells to AGEs resulted in release of ROS (P < 0.05) with significant (P <
      0.05) decline in antioxidant enzyme levels and increase in collagen (P < 0.01)
      content. In addition, the altered mitochondrial membrane potential (mmp) (P <
      0.01) was also observed in cells exposed to AGEs, whereas AGEs-exposed cells
      pretreated with GA prevented the release of ROS, and there were no significant
      changes in the antioxidant status, collagen content and mmp. Thus, the results of
      the present study provide evidence that GA exhibits protective role against AGEs
      induced cardiovascular complications probably through its free radical scavenging
      activity.

PMID- 22588842
TI  - Adverse effects of permanent atrial fibrillation on heart failure in patients
      with preserved left ventricular function and chronic right apical pacing for
      complete heart block.
AB  - BACKGROUND: The impact of atrial fibrillation (AF) on heart failure (HF) was
      evaluated in patients with preserved left ventricular (LV) function and long-term
      right ventricular (RV) pacing for complete heart block. METHODS: Clinical,
      echocardiographic, and laboratory parameters of HF were assessed in 35 patients
      with established AF who had undergone ablation of the atrioventricular node and
      pacemaker implantation (Group A) and 31 patients who received dual-chamber pacing
      for spontaneous complete heart block (Group B). RESULTS: During a follow-up
      period of 12.7 +/- 7.5 years, New York Heart Association (NYHA) functional class
      increased from 1.3 +/- 0.5 to 2.1 +/- 0.6 (p < 0.0001) in Group A, and from 1.3
      +/- 0.4 to 1.6 +/- 0.7 (p < 0.01) in Group B. Left ventricular ejection fraction
      (LVEF) decreased from 59.7 +/- 5.1 to 53.0 +/- 8.2 (p < 0.0001) in Group A, but
      remained stable (58.6 +/- 4.2 vs. 56.9 +/- 7.0 %, p = 0,21) in Group B. At the
      end of follow-up, markers of LV function were moderately depressed in Group A
      compared with those in Group B: NYHA class 2.1 +/- 0.6 versus 1.6 +/- 0.7, p =
      0.001; LVEF 53.0 +/- 8.2 versus 56.9 +/- 7.0 %, p < 0.05; LV diastolic diameter
      53.6 +/- 5.8 mm versus 50.7 +/- 4.9 mm, p < 0.05; N-terminal pro-brain
      natriuretic peptide (NT-proBNP) 1116.8 +/- 883.9 versus 622.9 +/- 1059.4 pg/ml, p
      < 0.05. Progression of paroxysmal AF to permanent AF during follow-up was common,
      while new onset of AF was rare. Permanent AF was an independent predictor of
      declining LVEF >10 %, increasing NYHA class >=1, and NT-proBNP levels >1,000
      pg/ml. CONCLUSIONS: Permanent AF was associated with adverse effects on LV
      function and symptoms of HF in patients with long-term RV pacing for complete
      heart block, and appears to play an important role in the development of HF in
      this specific patient cohort.

PMID- 22588843
TI  - Long-term clinical outcomes following sirolimus-eluting stent implantation in
      patients with acute myocardial infarction. A meta-analysis of randomized trials.
AB  - OBJECTIVES: The aim of this study was to perform a meta-analysis of randomized
      trials, evaluating the long-term outcomes of sirolimus-eluting stents (SES)
      versus bare-metal stents (BMS) in patients with ST-segment elevation myocardial
      infarction (STEMI). BACKGROUND: Despite short-term outcomes of patients with
      STEMI undergoing primary percutaneous coronary intervention indicate a benefit of
      SES in terms of reintervention, several concerns remain on the long-term safety
      and efficacy of SES. METHODS: A systematic literature search of electronic
      resources, through October 2011, was performed using specific search terms.
      Included trials were randomized studies comparing SES to BMS in STEMI patients,
      with a follow-up >=3 years. RESULTS: Seven trials were included, with a total of
      2,364 patients. At a median follow-up of 3 years, SES significantly reduced the
      risk of target-vessel revascularization when compared with BMS [odds ratio (OR),
      0.44; 95 % confidence interval (CI), 0.34-0.57; p < 0.0001], without increasing
      the risk of mortality (OR 0.78; 95 % CI, 0.57-1.08; p = 0.14), reinfarction (OR
      0.91; 95 % CI, 0.61-1.35, p = 0.64) and early to late stent thrombosis (OR 0.77;
      95 % CI, 0.49-1.20; p = 0.25). However after the first year, SES did not further
      reduce target-vessel revascularization (OR 1.06; 95 % CI, 0.64-1.74; p = 0.83)
      and increased the risk of very late stent thrombosis (OR 2.81; 95 % CI, 1.33
      5.92; p = 0.007). CONCLUSIONS: At long-term follow-up, SES compared to BMS use in
      STEMI patients reduces the risk of target-vessel revascularization, without
      increasing the risk of death and reinfarction. However, the strong SES efficacy
      is counterbalanced by a significant risk of very late stent thrombosis.

PMID- 22588844
TI  - Effect of transcatheter aortic valve implantation on the ascending aorta's
      elasticity.
AB  - BACKGROUND: The elastic properties of the ascending aorta were studied before and
      1 week after transcatheter aortic valve implantation (TAVI). Previous studies
      have shown that the distensibility of the ascending aorta was decreased in the
      early post-operative period after aortic valve replacement. Aortic stiffness is a
      major moderator of arterio-ventricular coupling and an independent predictor of
      cardiovascular risk and mortality. We evaluated the effect of TAVI on the elastic
      properties of the ascending aorta in the early post-operative period. METHODS:
      Aortic distensibility (AD) and Aortic Stiffness Index (ASI) were evaluated using
      echocardiographic techniques and brachial artery pressure obtained by
      sphygmomanometry 2-3 days before and 7-8 days after TAVI. RESULTS: A total of 30
      patients (14 males) were studied with a mean age of 79.9 +/- 4.7 years and aortic
      valve area before TAVI of 0.61 +/- 0.16 cm(2). Mean arterial pressure decreased
      significantly after TAVI (from 89.6 +/- 8.9 mmHg to 83.3 +/- 10.9 mmHg, p =
      0.004). AD did not change significantly after TAVI (pre: 1.89 +/- 1.11
      cm(2)/(dynes * 10(6)), post: 2.05 +/- 1.50 cm(2)/(dynes * 10(6)); p = 0.813). ASI
      also remained unchanged (pre: 11.4 +/- 6.5, post: 15.6 +/- 14.9; p = 0.349).
      CONCLUSIONS: The elastic properties of the ascending aorta did not change
      significantly in the early post-procedural period after TAVI. This may in part be
      attributable to the less invasive procedure (compared to aortic valve
      replacement) which has no effect on vasa vasorum flow.

PMID- 22588845
TI  - How to define green adjuvants.
AB  - The concept 'green adjuvants' is difficult to define. This paper formulates an
      answer based on two approaches. Starting from the Organisation for Economic
      Cooperation and Development (OECD) definition for green chemistry, production
      based and environmental-impact-based definitions for green adjuvants are
      proposed. According to the production-based approach, adjuvants are defined as
      green if they are manufactured using renewable raw materials as much as possible
      while making efficient use of energy, preferably renewable energy. According to
      the environmental impact approach, adjuvants are defined as green (1) if they
      have a low human and environmental impact, (2) if they do not increase active
      ingredient environmental mobility and/or toxicity to humans and non-target
      organisms, (3) if they do not increase the exposure to these active substances
      and (4) if they lower the impact of formulated pesticides by enhancing the
      performance of active ingredients, thus potentially lowering the required dosage
      of active ingredients. Based on both approaches, a tentative definition for
      'green adjuvants' is given, and future research and legislation directions are
      set out.

PMID- 22588846
TI  - Improvement of type 2 diabetes mellitus (T2DM) after bariatric surgery--who fails
      in the early postoperative course?
AB  - BACKGROUND: Diabetes surgery in nonobese or moderately obese patients is an
      emerging topic. The identification of preoperative factors predicting diabetes
      outcome following bariatric surgery, especially for metabolic nonresponders, is
      imperative. METHODS: Between 2005 and 2011, 235 patients underwent bariatric
      surgery for morbid obesity. Eighty-two of 235 patients had type 2 diabetes
      mellitus (T2DM). Data from this subgroup were investigated with univariate and
      multivariate analyses to identify predictors for metabolic nonresponse after
      surgery. RESULTS: Diabetes did not improve in 17/82 patients within 3 months
      after surgery. No correlation between excess body weight loss and metabolic
      response was detected. In univariate analysis, preoperative duration of diabetes
      was significantly longer in the nonresponder group (9.146 vs. 6.270 years; *p =
      0.016), preoperative HbA1c levels were significantly higher among the
      nonresponders than among the responders (8.341 vs. 7.781 %; *p = 0.033), and more
      patients in the nonresponder group were reliant on a multi-drug approach
      preoperatively (*p = 0.045). In multivariate analysis, age, preoperative doses of
      insulin, and preoperative oral antidiabetics showed positive correlation to
      metabolic nonresponse after surgery (*p = 0.04; *p = 0.021; *p = 0.021).
      Metabolic failure rate was lower after Roux-en-Y gastric bypass compared to other
      bariatric procedures (**p = 0.008). CONCLUSIONS: A long history of preoperative
      T2DM, high preoperative HbA1c levels, and a preoperative therapy consisting of
      diverse approaches to diabetes treatment may be factors predicting failure of
      diabetes improvement in the early postoperative course after bariatric surgery.
      Age, preoperative insulin, and oral antidiabetic medication can be regarded as
      independent, significant predictors for metabolic outcome after bariatric
      surgery.

PMID- 22588847
TI  - Comparative reaction engineering studies for succinic acid production from
      sucrose by metabolically engineered Escherichia coli in fed-batch-operated
      stirred tank bioreactors.
AB  - This study presents a comparative reaction engineering analysis of metabolically
      engineered sucrose-utilizing Escherichia coli derived from E. coli K12 MG1655 for
      the anaerobic production of succinic acid. Production capacities of 16 different
      recombinant strains were evaluated in 48 parallel fed-batch-operated milliliter
      scale stirred tank bioreactors (10 mL) with continuous CO2 sparging. The effects
      of recombinant sucrose-utilization systems (csc-operon or scr-operon),
      enhancements of anaplerotic reactions (pck, ppc, maeA, maeB or heterologous pyc)
      and gene deletions (ldhA, adhE, ack-pta and ptsG) were studied with respect to
      the overall process performances of the respective recombinant strains. Both
      sucrose-utilization systems enabled the production of succinic acid from sucrose
      in E. coli K12 MG1655. Maximum succinate production was observed by
      overexpressing the pyruvate carboxylase from Corynebacterium glutamicum resulting
      in a succinate concentration of 26.8 g L-1 after 48 h and a cell-specific
      productivity of 0.14 g g-1 h-1. Further experiments in a fed-batch-operated
      laboratory-scale stirred tank bioreactor (2 L) showed that micro-aerobic
      conditions preceding the anaerobic phase enhance succinic acid production of E.
      coli K12 MG1655-derived strains. The work demonstrates the importance of parallel
      approaches within the scope of applied metabolic engineering studies.

PMID- 22588848
TI  - Post-doffing residual limb fluid volume change in people with trans-tibial
      amputation.
AB  - BACKGROUND: Residual limb volume may change after doffing, affecting the limb
      shape measured and used as a starting point for socket design. OBJECTIVES: The
      purpose of this study was to compare residual limb fluid volume changes after
      doffing for different test configurations. STUDY DESIGN: The study was a repeated
      measures experimental design with three conditions (Sit, Liner, and Walk).
      METHODS: Residual limb fluid volume on 30 people with trans-tibial amputation was
      measured using bioimpedance analysis. Three tests were conducted--Sit: sit for 10
      minutes, remove the prosthesis, socks and liner, sit for 10 minutes; Liner: sit
      for 10 minutes, remove the prosthesis and socks but not the liner, sit for 10
      minutes; Walk: conduct sit, stand and walk activities for 30 minutes, remove the
      prosthesis, socks and liner, sit for 10 minutes. RESULTS: The percentage fluid
      volume increase after doffing was significantly higher for Walk (2.8%) than for
      Sit (1.8%) (p = 0.03). The time to achieve a maximum or stable fluid volume was
      shorter for Liner (4.3 min) than for Sit (6.6 min) (p = 0.03). CONCLUSIONS:
      Activity before doffing intensified the post-doffing limb fluid volume increase.
      Maintaining a liner after doffing caused limb fluid volume to stabilize faster
      than removing the liner. Clinical relevance To minimize residual limb volume
      increase before casting or imaging, practitioners should have patients sit with
      their prosthesis donned for 10 minutes. Leaving a liner on the residuum will not
      reduce the post-doffing volume increase, but it will help to more quickly achieve
      a consistent limb fluid volume.

PMID- 22588849
TI  - Reciprocal gait orthoses and powered gait orthoses for walking by spinal cord
      injury patients.
AB  - BACKGROUND: Using mechanical orthoses have some limitations for walking in
      paraplegic patients. The development of powered orthoses could potentially
      overcome some of the limitations of those currently available. OBJECTIVES: The
      aim of this review was to compare the evidence of the effect of powered gait
      orthoses (PGOs) when compared to reciprocating gait orthoses (RGOs) and also hip
      guidance orthoses (HGOs) in improving gait parameters and the energy efficiency
      of walking by spinal cord injury (SCI) patients. STUDY DESIGN: Literature review.
      METHODS: Using the PRISMA method, and based on selected keywords and their
      composition, a search was performed in PubMed, Science Direct, and ISI Web of
      Knowledge databases. Eight articles were selected for final evaluation. RESULTS:
      The results of the analysis demonstrated that there is lack of evidence to show
      that currently-developed powered orthoses improve the walking parameters of SCI
      patients when compared to RGOs and HGOs. CONCLUSIONS: The changes offered by PGOs
      are not substantial enough for such orthoses to be currently considered
      preferable by SCI subjects for ambulatory purposes. Clinical relevance The
      development of powered orthoses is still in its infancy and progress needs to be
      made to improve their functionality and performance envelopes.

PMID- 22588850
TI  - Smoking status on outcomes after percutaneous coronary intervention.
AB  - BACKGROUND: The effect of smoking on prognosis among patients undergoing
      percutaneous coronary intervention (PCI) is controversial, and data on the
      importance of smoking cessation or reductions were lacking. HYPOTHESIS: Smoking
      cessation or reductions could reduce the risk of adverse outcomes in patient
      after PCI. METHODS: There were 19 506 consecutive patients who had undergone
      successful PCI between April 2004 and January 2010 followed. Extensive data,
      including self-reported smoking habits, were obtained at baseline and during
      follow-up. RESULTS: Compared with post-PCI quitters and persistent smokers, the
      nonsmokers and pre-PCI quitters were older and had a higher prevalence of
      comorbid factors such as hypertension and impaired left ventricle function. The
      adjusted hazard ratios for mortality were 2.52 (95% confidence interval [CI]:
      1.92-3.30) for nonsmokers, 0.52 (95% CI: 0.32-0.84) for pre-PCI quitters, and
      0.11 (95% CI: 0.06-0.22) for post-PCI quitters, compared to persistent smokers.
      With respect to additional revascularizations, a higher risk was observed among
      the quitters (1.70 [95% CI: 1.40-2.08] for pre-PCI quitters and 1.59 [95% CI:
      1.36-1.85] for post-PCI quitters) as well as the nonsmokers (1.40 [95% CI: 1.20
      1.64]). Among persistent smokers, each reduction of 5 cigarettes/day was
      associated with a 72% decline in mortality risk (P < 0.001) but did not reach
      statistical significant for repeated revascularizations (0.80 [95% CI: 0.46
      1.37], P = 0.4132). CONCLUSIONS: Despite a higher risk of revascularization, the
      cessation of smoking either before or after PCI is beneficial in all-cause
      mortality. The apparent smoker's paradox may be explained by the differences in
      baseline risk or the reduced sensitivity to adverse outcomes as well as the
      reluctance to seek medical help among smokers.

PMID- 22588851
TI  - Ruthenium-catalyzed redox isomerization of trifluoromethylated allylic alcohols:
      mechanistic evidence for an enantiospecific pathway.
AB  - Transfer news: A synthetic approach to chiral beta-CF(3)-substituted saturated
      carbonyl compounds has been developed in which ruthenium complexes efficiently
      catalyze the redox isomerization of CF(3)-bearing allylic alcohols by an
      intramolecular suprafacial enantiospecific 1,3-hydrogen transfer (see scheme).
      This method was used for the enantioselective synthesis of (S)-CF(3)-citronellol.

PMID- 22588852
TI  - Efficacy of methylprednisolone in children with severe community acquired
      pneumonia.
AB  - BACKGROUND: The clinical value of adjuvant corticosteroid treatment in community
      acquired pneumonia (CAP) seemed to be controversial in adults, and even less data
      are available on the use of corticosteroids in children with CAP. MATERIALS AND
      METHODS: In this study, we investigated the efficacy of a 5-day adjuvant
      methylprednisolone therapy to imipenem in 29 children with severe CAP. In
      parallel, 30 subjects with the same disease were treated with imipenem and
      placebo, and the two study groups were compared based on the different parameters
      of the primary and secondary end points. The primary end points were the duration
      of fever, the levels of white blood cells (WBC) and high sensitive C-reactive
      protein (hsCRP). Secondary end points were the length of hospital stay, and the
      number of severe complications with or without surgical interventions. RESULTS:
      The additive methylprednisolone treatment significantly reduced the duration of
      fever with 2.5 days, the WBC counts (P = 0.014), the hsCRP levels showing a 48.7%
      decrease, and the length of hospital stay with 5.2 days versus the placebo group.
      Moreover, patients treated on imipenem alone had twice more complications and
      four times more invasive interventions compared to those on the combined therapy.
      CONCLUSIONS: The 5-day methylprednisolone therapy with imipenem was found
      effective in children having severe CAP. However, trials with larger cohorts are
      needed to study further beneficial effects of corticosteroids in children with
      CAP.

PMID- 22588853
TI  - Interactions between deliberation and delay-discounting in rats.
AB  - When faced with decisions, rats sometimes pause and look back and forth between
      possible alternatives, a phenomenon termed vicarious trial and error (VTE). When
      it was first observed in the 1930s, VTE was theorized to be a mechanism for
      exploration. Later theories suggested that VTE aided the resolution of sensory or
      neuroeconomic conflict. In contrast, recent neurophysiological data suggest that
      VTE reflects a dynamic search and evaluation process. These theories make unique
      predictions about the timing of VTE on behavioral tasks. We tested these theories
      of VTE on a T-maze with return rails, where rats were given a choice between a
      smaller reward available after one delay or a larger reward available after an
      adjustable delay. Rats showed three clear phases of behavior on this task:
      investigation, characterized by discovery of task parameters; titration,
      characterized by iterative adjustment of the delay to a preferred interval; and
      exploitation, characterized by alternation to hold the delay at the preferred
      interval. We found that VTE events occurred during adjustment laps more often
      than during alternation laps. Results were incompatible with theories of VTE as
      an exploratory behavior, as reflecting sensory conflict, or as a simple
      neuroeconomic valuation process. Instead, our results were most consistent with
      VTE as reflecting a search process during deliberative decision making. This
      pattern of VTE that we observed is reminiscent of current navigational theories
      proposing a transition from a deliberative to a habitual decision-making
      mechanism.

PMID- 22588860
TI  - Q&A: Michael Pellini on cancer diagnostics. Interview by Eric Bender.

PMID- 22588861
TI  - The states of research.

PMID- 22588862
TI  - Cancer stem cells in the crosshairs.

PMID- 22588873
TI  - Making sense of MEK1 mutations in intrinsic and acquired BRAF inhibitor
      resistance.
AB  - In this issue of Cancer Discovery, Shi and colleagues add further insight into
      the role of exon 3 MEK1 mutations in BRAF inhibitor resistance by demonstrating
      the presence of P124SMEK1 and I111SMEK1 mutations concurrently with V600E/KBRAF
      mutations at baseline in 16% of melanoma specimens. Although the presence of
      P124SMEK1 or I111SMEK1 mutations did not predict for resistance, and these
      alleles were not selected for upon BRAF inhibition, other exon 3 MEK1 mutations,
      such as C121S, did convey resistance, suggesting a role for defined exon 3 MEK1
      mutations in acquired BRAF inhibitor resistance.

PMID- 22588874
TI  - Beta-testing of PI3-kinase inhibitors: is beta better?
AB  - Although it has been known for some time that PTEN-null tumors require expression
      of the p110beta isoform of phosphoinositide 3-kinase for growth, the corollary
      demonstration that small-molecule inhibitors of p110beta are effective drugs for
      such tumors has not been shown. This has now been rectified by the demonstration
      that the TGX221 analogue KIN-193 is effective in mouse xenografts of HCC70 and
      PC3 human tumor cell lines.

PMID- 22588875
TI  - Circulating endothelial progenitors and tumor resistance to vascular-targeting
      therapies.
AB  - Acute mobilization of circulating endothelial progenitors has been implicated in
      tumor resistance to vascular-disrupting agents. In the current issue of Cancer
      Discovery, Taylor and colleagues provide novel insight into the kinetics of
      endothelial progenitor mobilization by vascular-disrupting agents in both mouse
      tumor models and cancer patients.

PMID- 22588876
TI  - Occupy EGFR.
AB  - Erlotinib and gefitinib inhibit the growth of non-small cell lung cancer tumors
      that harbor activating epidermal growth factor receptor (EGFR) mutations but are
      ineffective against EGFR variants found in glioblastoma. New studies by Barkovich
      and colleagues and Vivanco and colleagues show that these drugs only occupy the
      active sites of glioblastoma-derived EGFR mutants to a limited extent and fail to
      inhibit the activated receptor. Other EGFR inhibitors that target distinct
      receptor conformations are more effective in the treatment of glioblastoma. These
      studies reveal distinct drug selectivities for different EGFR mutations and show
      that an analysis of binding-site occupancy should be considered as a biomarker
      for inhibitor efficacy in targeting EGFR.

PMID- 22588877
TI  - The cBio cancer genomics portal: an open platform for exploring multidimensional
      cancer genomics data.
AB  - The cBio Cancer Genomics Portal (http://cbioportal.org) is an open-access
      resource for interactive exploration of multidimensional cancer genomics data
      sets, currently providing access to data from more than 5,000 tumor samples from
      20 cancer studies. The cBio Cancer Genomics Portal significantly lowers the
      barriers between complex genomic data and cancer researchers who want rapid,
      intuitive, and high-quality access to molecular profiles and clinical attributes
      from large-scale cancer genomics projects and empowers researchers to translate
      these rich data sets into biologic insights and clinical applications.

PMID- 22588878
TI  - Emerging epigenetic targets and therapies in cancer medicine.
AB  - Abnormalities in the epigenetic regulation of chromatin structure and function
      can lead to aberrant gene expression and cancer development. Consequently,
      epigenetic therapies aim to restore normal chromatin modification patterns
      through the inhibition of various components of the epigenetic machinery. Histone
      deacetylase and DNA methyltransferase inhibitors represent the first putative
      epigenetic therapies; however, these agents have pleiotropic effects and it
      remains unclear how they lead to therapeutic responses. More recently, drugs that
      inhibit histone methyltransferases were developed, perhaps representing more
      specific agents. We review emerging epigenetic targets in cancer and present
      recent models of promising epigenetic therapies. SIGNIFICANCE: The use of DNA
      methyltransferase and histone deacetylase inhibitors in patients has validated
      the use of drugs targeted to epigenetic enzymes and strengthened the need for
      development of additional therapies. In this review, we summarize recently
      discovered epigenetic abnormalities, their implications for cancer, and the
      approaches taken for discovering small-molecule inhibitors targeting various
      properties of the epigenetic machinery.

PMID- 22588879
TI  - Preexisting MEK1 exon 3 mutations in V600E/KBRAF melanomas do not confer
      resistance to BRAF inhibitors.
AB  - BRAF inhibitors (BRAFi) induce antitumor responses in nearly 60% of patients with
      advanced V600E/KBRAF melanomas. Somatic activating MEK1 mutations are thought to
      be rare in melanomas, but their potential concurrence with V600E/KBRAF may be
      selected for by BRAFi. We sequenced MEK1/2 exon 3 in melanomas at baseline and
      upon disease progression. Of 31 baseline V600E/KBRAF melanomas, 5 (16%) carried
      concurrent somatic BRAF/MEK1 activating mutations. Three of 5 patients with
      BRAF/MEK1 double-mutant baseline melanomas showed objective tumor responses,
      consistent with the overall 60% frequency. No MEK1 mutation was found in disease
      progression melanomas, except when it was already identified at baseline. MEK1
      mutant expression in V600E/KBRAF melanoma cell lines resulted in no significant
      alterations in p-ERK1/2 levels or growth-inhibitory sensitivities to BRAFi,
      MEK1/2 inhibitor (MEKi), or their combination. Thus, activating MEK1 exon 3
      mutations identified herein and concurrent with V600E/KBRAF do not cause BRAFi
      resistance in melanoma. SIGNIFICANCE: As BRAF inhibitors gain widespread use for
      treatment of advanced melanoma, biomarkers for drug sensitivity or resistance are
      urgently needed. We identify here concurrent activating mutations in BRAF and
      MEK1 in melanomas and show that the presence of a downstream mutation in MEK1
      does not necessarily make BRAF-mutant melanomas resistant to BRAF inhibitors.

PMID- 22588881
TI  - Reversing resistance to vascular-disrupting agents by blocking late mobilization
      of circulating endothelial progenitor cells.
AB  - The prevailing concept is that immediate mobilization of bone marrow-derived
      circulating endothelial progenitor cells (CEP) is a key mechanism mediating tumor
      resistance to vascular-disrupting agents (VDA). Here, we show that administration
      of VDA to tumor-bearing mice induces 2 distinct peaks in CEPs: an early,
      unspecific CEP efflux followed by a late yet more dramatic tumor-specific CEP
      burst that infiltrates tumors and is recruited to vessels. Combination with
      antiangiogenic drugs could not disrupt the early peak but completely abrogated
      the late VDA-induced CEP burst, blunted bone marrow-derived cell recruitment to
      tumors, and resulted in striking antitumor efficacy, indicating that the late CEP
      burst might be crucial to tumor recovery after VDA therapy. CEP and circulating
      endothelial cell kinetics in VDA-treated patients with cancer were remarkably
      consistent with our preclinical data. These findings expand the current
      understanding of vasculogenic "rebounds" that may be targeted to improve VDA
      based strategies. SIGNIFICANCE: Our findings suggest that resistance to VDA
      therapy may be strongly mediated by late, rather than early, tumor-specific
      recruitment of CEPs, the suppression of which resulted in increased VDA-mediated
      antitumor efficacy. VDA-based therapy might thus be significantly enhanced by
      combination strategies targeting late CEP mobilization.

PMID- 22588880
TI  - Functional characterization of an isoform-selective inhibitor of PI3K-p110beta as
      a potential anticancer agent.
AB  - Genetic approaches have shown that the p110beta isoform of class Ia
      phosphatidylinositol-3-kinase (PI3K) is essential for the growth of PTEN-null
      tumors. Thus, it is desirable to develop p110beta-specific inhibitors for cancer
      therapy. Using a panel of PI3K isoform-specific cellular assays, we screened a
      collection of compounds possessing activities against kinases in the PI3K
      superfamily and identified a potent and selective p110beta inhibitor: KIN-193. We
      show that KIN-193 is efficacious specifically in blocking AKT signaling and tumor
      growth that are dependent on p110beta activation or PTEN loss. Broad profiling
      across a panel of 422 human tumor cell lines shows that the PTEN mutation status
      of cancer cells strongly correlates with their response to KIN-193. Together, our
      data provide the first pharmacologic evidence that PTEN-deficient tumors are
      dependent on p110beta in animals and suggest that KIN-193 can be pursued as a
      drug to treat tumors that are dependent on p110beta while sparing other PI3K
      isoforms. SIGNIFICANCE: We report the first functional characterization of a
      p110beta-selective inhibitor, KIN-193, that is efficacious as an antitumor agent
      in mice. We show that this class of inhibitor holds great promise as a
      pharmacologic agent that could be used to address the potential therapeutic
      benefit of treating p110beta-dependent PTEN-deficient human tumors.

PMID- 22588882
TI  - Kinetics of inhibitor cycling underlie therapeutic disparities between EGFR
      driven lung and brain cancers.
AB  - Although mutational activation of the epidermal growth factor receptor (EGFR)
      features prominently in glioma and non-small cell lung cancer (NSCLC), inhibitors
      of EGFR improve survival only in patients with NCSLC. To understand how mutations
      in EGFR influence response to therapy, we generated glioma cells expressing
      either glioma- or NSCLC-derived alleles and quantified kinase-site occupancy by
      clinical inhibitors with the use of a novel affinity probe and kinetic
      methodology. At equivalent doses, erlotinib achieved lower kinase-site occupancy
      in glioma-derived EGFRvIII compared with NSCLC-derived EGFR mutants. Kinase-site
      occupancy correlated directly with cell-cycle arrest. EGFRvIII released erlotinib
      rapidly compared with wild-type EGFR, whereas NSCLC-derived mutants released
      erlotinib slowly. SIGNIFICANCE: These data suggest that kinase-site occupancy is
      a biomarker for efficacy of EGFR inhibitors, that rapid binding and release of
      erlotinib in glioma-derived EGFRvIII opposes the blockade of downstream
      signaling, and that slower cycling of erlotinib within the active site of NSCLC
      derived mutants underlies their improved clinical response.

PMID- 22588896
TI  - Strong hard X-ray magnetochiral dichroism in paramagnetic enantiopure molecules.

PMID- 22588883
TI  - Differential sensitivity of glioma- versus lung cancer-specific EGFR mutations to
      EGFR kinase inhibitors.
AB  - Activation of the epidermal growth factor receptor (EGFR) in glioblastoma (GBM)
      occurs through mutations or deletions in the extracellular (EC) domain. Unlike
      lung cancers with EGFR kinase domain (KD) mutations, GBMs respond poorly to the
      EGFR inhibitor erlotinib. Using RNAi, we show that GBM cells carrying EGFR EC
      mutations display EGFR addiction. In contrast to KD mutants found in lung cancer,
      glioma-specific EGFR EC mutants are poorly inhibited by EGFR inhibitors that
      target the active kinase conformation (e.g., erlotinib). Inhibitors that bind to
      the inactive EGFR conformation, however, potently inhibit EGFR EC mutants and
      induce cell death in EGFR-mutant GBM cells. Our results provide first evidence
      for single kinase addiction in GBM and suggest that the disappointing clinical
      activity of first-generation EGFR inhibitors in GBM versus lung cancer may be
      attributed to the different conformational requirements of mutant EGFR in these 2
      cancer types. SIGNIFICANCE: Approximately 40% of human glioblastomas harbor
      oncogenic EGFR alterations, but attempts to therapeutically target EGFR with
      first-generation EGFR kinase inhibitors have failed. Here, we demonstrate
      selective sensitivity of glioma-specific EGFR mutants to ATP-site competitive
      EGFR kinase inhibitors that target the inactive conformation of the catalytic
      domain.

PMID- 22588897
TI  - Dissection of complex adult traits in a mouse synthetic population.
AB  - Finding the causative genetic variations that underlie complex adult traits is a
      significant experimental challenge. The unbiased search strategy of genome-wide
      association (GWAS) has been used extensively in recent human population studies.
      These efforts, however, typically find only a minor fraction of the genetic loci
      that are predicted to affect variation. As an experimental model for the analysis
      of adult polygenic traits, we measured a mouse population for multiple phenotypes
      and conducted a genome-wide search for effector loci. Complex adult phenotypes,
      related to body size and bone structure, were measured as component phenotypes,
      and each subphenotype was associated with a genomic spectrum of candidate
      effector loci. The strategy successfully detected several loci for the
      phenotypes, at genome-wide significance, using a single, modest-sized population
      (N = 505). The effector loci each explain 2%-10% of the measured trait variation
      and, taken together, the loci can account for over 25% of a trait's total
      population variation. A replicate population (N = 378) was used to confirm
      initially observed loci for one trait (femur length), and, when the two groups
      were merged, the combined population demonstrated increased power to detect loci.
      In contrast to human population studies, our mouse genome-wide searches find loci
      that individually explain a larger fraction of the observed variation. Also, the
      additive effects of our detected mouse loci more closely match the predicted
      genetic component of variation. The genetic loci discovered are logical
      candidates for components of the genetic networks having evolutionary
      conservation with human biology.

PMID- 22588899
TI  - CIC and FUBP1 mutations in oligodendrogliomas, oligoastrocytomas and
      astrocytomas.
AB  - CIC and FUBP1 mutations have recently been detected in oligodendrogliomas but not
      in oligoastrocytomas. However, allelic losses in the regions on chromosomal arms
      19q and 1p harboring CIC and FUBP1 are a common feature of both,
      oligodendrogliomas and oligoastrocytomas. To resolve this discrepancy, we
      analyzed CIC and FUBP1 mutations in a set of primary brain tumors including 18
      oligodendrogliomas and 42 oligoastrocytomas. In addition, we analyzed 10
      astrocytomas and 16 glioblastomas with allelic losses on 19q as well as a set of
      12 medulloblastomas for CIC mutations. CIC mutations were found in 15/18
      oligodendrogliomas, 14/42 oligoastrocytomas and 3/10 preselected astrocytomas.
      With the exception of a single case, all CIC mutations occurred in tumors with
      combined 1p/19q losses. In contrast to oligodendrogliomas where CIC mutations
      were always detected along with 1p/19q co-deletion, CIC mutations were only found
      in 52 % of the 1p/19q co-deleted oligoastrocytomas. FUBP1 mutations were detected
      in 7/61 tumors, all presenting with CIC mutations. FUBP1 mutations appear to
      cluster in the DNA binding domain spanning exons 5-14. CIC and FUBP1 mutations
      exclusively occurred in presence of either IDH1 or IDH2 mutations. Our data
      confirm CIC and FUBP1 mutations in oligodendrogliomas and demonstrate the
      presence of these mutations in oligoastrocytomas.

PMID- 22588901
TI  - [Experimental early detection of acute mesenteric ischemia with functional MRI
      (DWI) and parallel imaging].
AB  - PURPOSE: To evaluate the feasibility of diagnosing in statu nascendi mesenteric
      ischemia using diffusion-weighted imaging (DWI) in a porcine model. All
      experiments were approved by the animal care committee at the district
      administration. MATERIALS AND METHODS: Mesenteric blood supply was studied in ten
      healthy female pigs (weight ~50 kg) with artificially induced mesenteric
      ischemia. In the DSA technique a branch of the superior mesenteric artery was
      embolized with tissue glue or small particles. DWI was performed using a 1.5 T MR
      scanner before embolization and 30 and 60 minutes after embolization using a 32
      channel receiver coil. ADC maps were calculated for all animals. The findings
      were correlated to angiographic and autoptic findings. The image quality of DWI
      was assessed by means of SNR measurements and diagnostic impact by CNR
      measurements. RESULTS: Embolization of the mesenteric branches was technically
      successful in all cases. DWI of the bowel was feasible with the applied
      sequences. In all animals, DWI displayed distinct cytotoxic edema as the earliest
      sign of ischemia thirty minutes after induction of ischemia. Furthermore, DWI
      yielded a distinct reduction in the water diffusion coefficient in all animals.
      Variance analysis showed good correlation between CNR measurements and infarction
      areas. Autoptic findings could confirm the detected infarction areas by DWI.
      CONCLUSION: DWI using parallel imaging techniques is feasible for the early
      detection of acute mesenteric ischemia. The presented DWI results offer
      encouraging prospects regarding more rapid disease diagnosis.

PMID- 22588898
TI  - Chimeras taking shape: potential functions of proteins encoded by chimeric RNA
      transcripts.
AB  - Chimeric RNAs comprise exons from two or more different genes and have the
      potential to encode novel proteins that alter cellular phenotypes. To date,
      numerous putative chimeric transcripts have been identified among the ESTs
      isolated from several organisms and using high throughput RNA sequencing. The few
      corresponding protein products that have been characterized mostly result from
      chromosomal translocations and are associated with cancer. Here, we
      systematically establish that some of the putative chimeric transcripts are
      genuinely expressed in human cells. Using high throughput RNA sequencing, mass
      spectrometry experimental data, and functional annotation, we studied 7424
      putative human chimeric RNAs. We confirmed the expression of 175 chimeric RNAs in
      16 human tissues, with an abundance varying from 0.06 to 17 RPKM (Reads Per
      Kilobase per Million mapped reads). We show that these chimeric RNAs are
      significantly more tissue-specific than non-chimeric transcripts. Moreover, we
      present evidence that chimeras tend to incorporate highly expressed genes.
      Despite the low expression level of most chimeric RNAs, we show that 12 novel
      chimeras are translated into proteins detectable in multiple shotgun mass
      spectrometry experiments. Furthermore, we confirm the expression of three novel
      chimeric proteins using targeted mass spectrometry. Finally, based on our
      functional annotation of exon organization and preserved domains, we discuss the
      potential features of chimeric proteins with illustrative examples and suggest
      that chimeras significantly exploit signal peptides and transmembrane domains,
      which can alter the cellular localization of cognate proteins. Taken together,
      these findings establish that some chimeric RNAs are translated into potentially
      functional proteins in humans.

PMID- 22588903
TI  - Structure-property optimizations in donor polymers via electronics, substituents,
      and side chains toward high efficiency solar cells.
AB  - Many advances in organic photovoltaic efficiency are not yet fully understood and
      new insight into structure-property relationships is required to push this
      technology into broad commercial use. The aim of this article is not to
      comprehensively review recent work, but to provide commentary on recent successes
      and forecast where researchers should look to enhance the efficiency of
      photovoltaics. By lowering the LUMO level, utilizing electron-withdrawing
      substituents advantageously, and employing appropriate side chains on donor
      polymers, researchers can elucidate further aspects of polymer-PCBM interactions
      while ultimately developing materials that will push past 10% efficiency.

PMID- 22588902
TI  - In vitro inhibition of mycelial growth of Phytophthora nicotianae Breda de Haan
      from different hosts by Brassicaceae species. Effect of the developmental stage
      of the biofumigant plants.
AB  - BACKGROUND: The hydrolysis products of glucosinolates in Brassicaceae tissues are
      potentially useful for the control of fungal pathogens. The in vitro activity of
      these products against Phytophthora nicotianae Breda de Haan was studied, with
      the isolates exposed to the volatile products released from the brassica tissues.
      RESULTS: The four species of Brassicaceae tested inhibited the mycelial growth of
      P. nicotianae isolates. The most effective developmental stage was different,
      depending on the species: buds yellowing in Sinapis alba L. and Brassica carinata
      A. Braun; seeds enlarging and all buds open in Brassica nigra (L.) W.D.J. Koch;
      cauliflower still covered by leaves in Brassica oleracea L. var. botrytis. At
      this stage, B. nigra and S. alba were the most effective (53.6 and 52.5%
      inhibition respectively). With all the biofumigants species tested, isolates from
      pepper plants were more susceptible to the brassica effect than those from tomato
      isolates. CONCLUSION: The developmental stage of plants has an influence on the
      biofumigant potential of Brassicaceae species against P. nicotianae. The isolates
      differ in susceptibility to compounds released, depending on their host of
      origin, suggesting the differentiation of populations of P. nicotianae in
      relation to the host of origin.

PMID- 22588904
TI  - Microinjection of NMDA-type glutamate receptor agonist NMDA and antagonist D-AP-5
      into the central nucleus of the amygdale alters water intake rather than food
      intake.
AB  - OBJECTIVE: To investigate the role of N-Methyl-D-aspartic acid (NMDA)-type
      glutamate receptors in the central nucleus of the amygdale (CeA) in food and
      water intake. METHODS: Male Sprague-Dawley rats with stainless steel cannulae
      implanted unilaterally into the CeA were used. The prototypic NMDA receptor
      agonist NMDA, or the selective NMDA receptor antagonist D(-)-2-amino-5
      phosphonopentanoic acid (D-AP-5) was microinjected into the CeA of satiated and
      euhydrated rats. RESULTS: Intra-CeA injection of 8.50, 17.00, or 34.00 nmol NMDA
      did not alter food intake but significantly increased water intake 0-1 h after
      the injection (F(3,32)=3.191, P=0.037) independent of food intake. Without
      affecting the food intake, injection of 6.34, 12.70, or 25.40 nmol D-AP-5 into
      the CeA significantly decreased water intake 0-1 h after the injection
      (F(3,28)=3.118, P=0.042) independent of food intake. CONCLUSION: NMDA receptors
      in the CeA may participate in the control of water intake rather than food
      intake.

PMID- 22588905
TI  - [Reliability and accuracy of arcuate fasciculus navigation: analysis of 43
      cases].
AB  - OBJECTIVE: To evaluate the reliability and accuracy of arcuate fasciculus (AF)
      navigation for AF localization and reconstruction. METHODS: Reconstruction of the
      AF and assessment of the aphasia quotient (AQ) were performed in 43 cases before
      and after surgical removal of lesions in the language area of the brain. The
      minimal distance between the AF and the lesion (D(1)), preoperative AQ (AQ(1)),
      the minimal distance between the AF and the surgical cavity (D(2)), and the
      postoperative AQ (AQ(2)) were measured. Linear correlation analysis was conducted
      between D(1) or D(2) and the corresponding AQ(1) or AQ(2) to assess the
      relationship between the AF and language function. The language function of each
      patient was evaluated postoperatively. RESULTS: The AF was successfully
      reconstructed in all the cases. The tractography results of the identical AF
      generated by 3 different users showed good congruency. A positive linear
      correlation was demonstrated between D(1) and AQ(1) (P<0.001) and between D(2)
      and AQ(2) (P=0.001). Only two patients (4.7%) showed language deficits at
      postoperative follow-up. CONCLUSION: AF navigation is a reliable and accurate
      technique for AF reconstruction and localization and helps to preserve the
      language function after surgical removal of lesions in the language area of the
      brain.

PMID- 22588906
TI  - [Inhibitory effect of sodium valproate on human lung carcinoma SPC-A1 cell
      proliferation and the mechanism].
AB  - OBJECTIVE: To observe the effect of sodium valproate (VPA) on the proliferation
      and apoptosis of human lung carcinoma SPC-A1 cells and the underlying mechanism.
      METHODS: The effect of VPA on the proliferation of SPC-A1 cells was evaluated by
      MTT assay and clone formation assay. Flow cytometry was used to analyze the
      apoptosis of the cells exposed to VPA. The changes in the expressions of Bcl-xl,
      Bcl-2, Mcl-1, caspase-9, and caspase-3 in the exposed cells were detected by
      Western blotting. RESULTS: Incubation with VPA for 48 h resulted in a significant
      inhibition of SPC-A1 cell proliferation, with a IC(50) of 1.8 mmol/L. VPA
      treatment also inhibited cell colony formation and induced obvious cell
      apoptosis. Exposure to 8 mmol/L VPA for 48 h caused a percentage of early
      apoptotic cells of 60.44%. VPA treatment at different concentrations for 48 h
      obviously lowered the protein levels of Bcl-xl, Bcl-2, and Mcl-1 and induced
      caspase-9 and caspase-3 activation in SPC-A1 cells. CONCLUSION: VPA can inhibit
      the proliferation of SPC-A1 cells by triggering mitochondrion-dependent
      apoptosis.

PMID- 22588907
TI  - [Sensitivity and specificity of nested PCR pyrosequencing in hepatitis B virus
      drug resistance gene testing].
AB  - OBJECTIVE: To evaluate the sensitivity and specificity of nested PCR combined
      with pyrosequencing in the detection of HBV drug-resistance gene. METHODS:
      RtM204I (ATT) mutant and rtM204 (ATG) nonmutant plasmids mixed at different
      ratios were detected for mutations using nested-PCR combined with pyrosequencing,
      and the results were compared with those by conventional PCR pyrosequencing to
      analyze the linearity and consistency of the two methods. Clinical specimens with
      different viral loads were examined for drug-resistant mutations using nested PCR
      pyrosequencing and nested PCR combined with dideoxy sequencing (Sanger) for
      comparison of the detection sensitivity and specificity. RESULTS: The fitting
      curves demonstrated good linearity of both conventional PCR pyrosequencing and
      nested PCR pyrosequencing (R(2)>0.99, P<0.05). Nested PCR showed a better
      consistency with the predicted value than conventional PCR, and was superior to
      conventional PCR for detection of samples containing 90% mutant plasmid. In the
      detection of clinical specimens, Sanger sequencing had a significantly lower
      sensitivity than nested PCR pyrosequencing (92% vs 100%, P<0.01). The detection
      sensitivity of Sanger sequencing varied with the viral loads, especially in
      samples with low viral copies (HBV DNA <=3log10 copies/ml), where the sensitivity
      was 78%, significantly lower than that of pyrosequencing (100%, P<0.01). Neither
      of the two methods yielded positive results for the negative control samples,
      suggesting their good specificity. CONCLUSION: Compared with nested PCR and
      Sanger sequencing method, nested PCR pyrosequencing has a higher sensitivity
      especially in clinical specimens with low viral copies, which can be important
      for early detection of HBV mutant strains and hence more effective clinical
      management.

PMID- 22588908
TI  - [Construction of a lentiviral vector for RNA interference of glycerol kinase gene
      in human hepatocytes in vitro].
AB  - OBJECTIVE: To construct a lentiviral vector for RNA interference (RNAi) of human
      glycerol kinase (GK) gene to stably down-regulate GK expression in human
      hepatocytes. METHODS: The sequence of siRNA for GK interference were cloned into
      the pSicoR vector. Following packaging in 293T cells, the lentivirus was titrated
      using fluorescence activated cell sorting. Human hepatocyte L02 cells was
      infected with the lentivirus and the expression of GK was analyzed using Western
      blotting. RESULTS: The lentiviral particle pSicoR-GK was successfully packaged
      with a virus titer reaching 3*10(7) pfu/ml. The expression level of GK protein
      was down-regulated to 20% of the control level in L02 cells infected with the
      lentivirus. CONCLUSION: The lentiviral vector for RNAi of human GK gene has been
      successfully constructed, which can significantly down-regulate GK expression in
      human hepatocytes.

PMID- 22588909
TI  - [Enhanced proliferation inhibition and apoptosis-inducing effects of docetaxel
      loaded lipid microbubble on human pancreatic cancer cells in vitro].
AB  - OBJECTIVE: To investigate the proliferation inhibition and apoptosis-inducing
      effect of docetaxel-loaded lipid microbubble (DLLM) combined with ultrasound
      targeted microbubble destruction (UTMD) on human pancreatic cancer cells in
      vitro. METHODS: DLLM was prepared by mechanical vibration, and its physical
      properties were characterized. The median inhibitory concentration (IC(50)) of
      DLLM was determined with MTT assay, and its cytotoxicity evaluated with cell
      counting Kit-8 (CCK-8) assay. The effects of docetaxel, DLLM, and DLLM combined
      with UTMD on cell cycle and apoptosis of BxPC3 cells were tested with flow
      cytometry (FCM) and TUNEL assay, respectively. RESULTS: DLLM had an average size
      of 1.6 um, and the average drug entrapment efficiency and drug-loaded amount was
      64.2% and 16.1%, respectively. Compared with the control groups, DLLM had a
      significantly enhanced cytotoxic effect (P<0.01) and caused an increased
      apoptosis rate in BxPC3 cells (P<0.01). Cell cycle analysis showed that DLLM
      combined with UTMD resulted in an significantly higher percentage of cells with
      G(2)/M phase arrest than the other treatments (P<0.01). CONCLUSIONS: DLLM
      combined with UTMD can increase G(2)/M phase arrest and enhance the proliferation
      inhibition and apoptosis-inducing effect on BxPC3 cells, and can serve as an
      effective drug delivery system for pancreatic cancer therapy.

PMID- 22588910
TI  - [Correlation between talonavicular joint movement and changes of the medial
      longitudinal arch].
AB  - OBJECTIVE: To explore the characteristics of the talonavicular joint movement in
      vivo and its effects on changes of the medial longitudinal arch. METHODS: Foot CT
      images in the initial position (neutral position) and terminal position (maximum
      varus-adduction-dorsiflexion position) were acquired from 9 cases (5 healthy
      volunteers, including 4 males and 1 female) during foot varus-adduction
      dorsiflexion motion. Based on the principle of rigid body kinematics, the CT data
      were reconstructed and analyzed with Mimics and Geomagic reverse engineering
      software. The changes of the talonavicular joint in three-dimensional in 6
      degrees of freedom were calculated to determine its correlation to the medial
      longitudinal arch angle. RESULTS: During foot varus-adduction-dorsiflexion
      motion, the talonavicular joint underwent varus-adduction-plantarflexion motion,
      with the motion range of 38.82?5.98 degrees  in varus, 19.71?6.33 degrees  in
      adduction, and -5.09?6.89 degrees  in plantarflexion. During talonavicular joint
      motion, the medial shift of the navicular was significantly correlated to the
      changes of foot medial longitudinal arch (P<0.05). CONCLUSION: Digital technology
      can solve the problem of measurement of talonavicular joint three-dimensional
      motion in vivo. Though as a ball-and-socket joint, the talonavicular joint mainly
      rotates around the sagittal axis, and its movement is a major factor to cause
      changes of foot medial longitudinal arch.

PMID- 22588911
TI  - [Construction of abridged life table for health evaluation of local resident
      using Excel program].
AB  - OBJECTIVE: To provide an easy computational tool for evaluating the health
      condition of local residents. METHODS: An abridged life table was programmed by
      applying mathematical functions and formula in Excel program and tested with the
      real study data to evaluate the results computed. RESULTS: The Excel was capable
      of computing group death probability of age in the life table ((n)q(x)), number
      of survivors (l(x)), number of death ((n)d(x)), survival per person-year
      ((n)L(x)), survival total per person-year (T(x)) and life expectancy (e(x)). The
      calculated results were consistent with those by SAS. CONCLUSION: The abridged
      life table constructed using Microsoft Excel can conveniently and accurately
      calculate the relevant indices for evaluating the health condition of the
      residents.

PMID- 22588912
TI  - [Serum miR-103 as a potential diagnostic biomarker for breast cancer].
AB  - OBJECTIVE: To evaluate the diagnostic value of serum miR-103 for breast cancer
      and its correlation to the clinicopathological features of the patients. METHODS:
      We collected the serum samples and corresponding formalin-fixed paraffin-embedded
      (FFPE) surgical specimens from 50 breast cancer patients, using the serum samples
      from 50 healthy women as the control. The total RNA was extracted from the
      samples for quantitative analysis of miR-103 using real-time RT-PCR. RESULTS: The
      serum levels of miR-103 expression were significantly higher in the cancer
      patients than in the healthy control group (P<0.01). In the cancer patients, high
      miR-103 expression was significantly correlated to advanced clinical stage
      (P<0.05) and lymph node metastasis (P<0.05). miR-103 showed a receiver operating
      characteristic (ROC) curve area of 84.3%, and a sensitivity of 84% and a
      specificity of 70% in discriminating breast cancer patients from the control
      subjects. CONCLUSION: Serum miR-103 can serve as a potential diagnostic marker
      for breast cancer and provides useful information of the clinicopathological
      features of the patients.

PMID- 22588913
TI  - [Expression of progesterone receptor membrane component-1 is associated with the
      malignant phenotypes of breast cancer].
AB  - OBJECTIVE: To investigate the correlation of the expression of progesterone
      receptor membrane component-1 to the clinicopathological features of breast
      cancer. METHODS: The expression of PGRMC1 was detected immunohistochemically in
      60 surgical specimens of breast cancer, and the association of PGRMC1 with the
      histological grade, lymphatic metastasis, TNM stage and prognosis was assessed.
      RESULTS: Positive CA-9 expression was detected in 37 (61.67%) of the cases.
      PGRMC1 expression was significantly correlated to lymph node metastasis
      (P=0.004), tumor size (P=0.03), TNM stage (P=0.039), overall survival rate (Log
      rank=10.378, P=0.0001), and tumor-free survival (Log-rank=4.443, P=0.035), but
      not to the patients' age (P=0.196) or histological grade (P=0.526). Multivariate
      survival analysis indicated that PGRMC1 was an independent prognostic factor of
      breast cancer (P=0.002). CONCLUSIONS: The expression of PGRMC1 is strongly
      associated with the progression of breast cancer, and may serve as a useful
      prognostic indicator of the malignancy.

PMID- 22588914
TI  - [Exogenous 3', 5'-cyclic diguanylic acid prevents caries formation in rats].
AB  - OBJECTIVE: To investigate the effect of exogenous c-di-GMP in preventing dental
      caries formation in SD rats. METHODS: Twenty-day-old SD rats with dental caries
      induced by S. Mutans infection were randomly divided into 3 groups for treatment
      with dental application of exogenous c-di-GMP, NaF solution or 0.9% NaCl, and
      changes in the bacterial number and scores of dental caries following the
      treatments were recorded. RESULTS: Compared with 0.9% NaCl treatment, exogenous c
      di-GMP treatment significantly lowered the scores of dental caries on the
      occlusal surface and smooth surface (P<0.05) but produced no obvious effect on
      the number of bacterial plagues (P>0.05). CONCLUSION: Exogenous c-di-GMP can be a
      novel agent for prevention and treatment of tooth decay.

PMID- 22588915
TI  - [Expression of OCT4 protein in bladder cancer and its clinicopathological
      implications].
AB  - OBJECTIVE: To study the expression of OCT4 protein in bladder cancer and its
      correlation to the clinicopathologic features and prognosis of bladder cancer.
      METHODS: OCT4 mRNA and protein expression was detected in 5 bladder cancer cell
      lines (RT-4, Tcc-Sup, KK47, T24, and 5637) and 1 normal bladder cell lines by
      real-time PCR and Western blotting, respectively. Immunohistochemical analysis
      was used to detect the expression of OCT4 protein in 46 bladder cancer samples.
      RESULTS: All the 5 bladder cancer cell lines expressed detectable levels of OCT4
      mRNA and proteins, whereas the normal bladder cell line SV-HUC-1 was negative for
      OCT4 expression. The clinical bladder cancer tissues showed a high positivity
      rate of OCT4 expression (76.1%), which was not detected in normal bladder
      tissues. Specific OCT-4 signals were localized mainly in the nuclei of the cancer
      cells. The expression rate of OCT4 protein was significantly higher in bladder
      cancer tissue than in normal bladder epithelium (P<0.05), and showed a positive
      correlation to the grade of tumor differentiation and metastasis (P<0.05) but not
      to the patients' age, gender or TNM stage. CONCLUSION: OCT4 protein expression is
      associated with tumor differentiation and metastasis in bladder cancer and may
      play an important role in the early diagnosis and prognostic evaluation of
      bladder cancer.

PMID- 22588916
TI  - [Screening and identification of peptides specifically binding to human
      osteosarcoma cells].
AB  - OBJECTIVE: To obtain the peptide that specifically binds to human osteosarcoma MG
      63 cells from Ph. D. 7TM phage display peptide library. METHODS: Human
      osteosarcoma MG-63 cells were used as the target cells with human embryonic
      kidney 293T cells as the control for screening the peptide from Ph. D. 7TM phage
      display peptide library. The enriched specially binding peptides were verified by
      cell enzyme-linked immunosorbent assay (ELISA). The location of the peptide in MG
      63 cells was investigated using cell fluorescence staining, and targeting of the
      peptide was tested by organ immunohistochemistry with Osteosarcoma model.
      RESULTS: The specifically binding peptides were enriched after 4 rounds of
      screening. The sequence SLTNLSK was confirmed as the most frequent peptide by DNA
      sequencing and showed strong specificity verified by cell ELISA, fluorescent
      staining and organ immunohistochemistry. CONCLUSION: A peptide that specifically
      binds to MG-63 cells has been screened from Ph. D. 7TM phage display peptide
      library to serve as a potential candidate for osteosarcoma-targeting therapy.

PMID- 22588917
TI  - [Impact of MICA antibodies on acute graft rejection early after kidney
      transplantation].
AB  - OBJECTIVE: To evaluate the influence of major histocompatibility complex class I
      chain-related gene A (MICA) antibodies on acute rejection (AR) and renal function
      in early stage after renal transplantation. METHODS: A total of 197 renal
      transplant candidates admitted in Nanfang Hospital in 2009-2010 were enrolled in
      this study. MICA antibodies and their specificity were detected in all the
      patients, and 139 patients were followed up for early acute rejection (AR) and
      graft function after transplantation. RESULTS: MICA antibodies were positive
      before transplantation in 45 candidates (22.84%). Eleven specific MICA antibodies
      were identified, among which the frequency of MICA019 antibody (65.7%) was
      significantly higher than that of MICA015 (8.6%) and MICA017 (8.6%) (P<0.01).
      Eighteen patients with positive MICA antibodies were single-specific and 17 were
      polyspecific (51.4% vs 48.6% ). Of the 139 patients undergoing renal
      transplantation, 39 developed early AR (28.1%). Of the 45 candidates positive for
      MICA antibodies, 38 received renal transplantation and early AR occurred in 14 of
      them (36.8%); 101 of 152 candidates negative for MICA antibodies underwent renal
      transplantation, and 25 experienced early AR (24.8%). CONCLUSION: MICA019
      antibody is a frequent MICA antibody possibly due to the high frequency MICA019
      gene in Chinese population.

PMID- 22588918
TI  - [An improved adaptive spectral clustering for image segmentation].
AB  - OBJECTIVE: To propose an improved adaptive spectral clustering method for image
      segmentation to allow automatic selection of the optimal scaling parameters and
      enhance the accuracy of spectral clustering. METHODS: Using constrain conditions
      for optimizing the criterion function and determining the optimal scaling
      parameters by iteration, the final image segmentation was achieved through
      spectral clustering based on Nystrom approximation. We chose suit weight
      functions for different texture images, and used the proposed method for image
      segmentation. The k-means algorithm and the method of spectral clustering after
      pre-segmentation by manually choosing the scaling parameter were compared with
      the proposed method. RESULTS: The improved spectral clustering algorithm with
      automatic selection of the optimal scaling parameters achieved better results of
      image segmentation than the other two methods. CONCLUSION: The proposed algorithm
      can improve the accuracy of spectral clustering for image segmentation.

PMID- 22588919
TI  - [Role of CD4(+)CD25(+) regulatory T cells and Foxp3 in the pathophysiology of
      acute cerebral ischemia in rats].
AB  - OBJECTIVE: To investigate the dynamic changes in CD4(+)CD25(+) regulatory T cells
      and Foxp3 expression in peripheral blood and brain tissues of rats after acute
      cerebral ischemia and explore their role in the pathophysiological evolution of
      acute ischemic stroke. METHODS: Forty-eight Wistar rats were randomized equally
      into ischemia and sham-operated groups, and right middle cerebral artery
      occlusion was induced in the former group. Flow cytometry and
      immunohistochemistry were employed to detect CD4(+)CD25(+) T cells and Foxp3
      expression, respectively, in the peripheral blood and brain tissue at 1, 3, 7,
      and 14 days after modeling. The behavioral changes of the rats were evaluated
      using an improved NSS neurological functional scoring system. RESULTS: The
      neurological function scores of the two groups both gradually declined after the
      operation, and showed significant differences between the two groups at all the
      time points of measurement (P<0.01). The CD4(+)CD25 T cells in the peripheral
      blood were similar between the two group at 1 and 3 days after the operation
      (P>0.05), but increased significantly in the ischemia group at 7 and 14 days
      (P<0.05) with an inverse correlation to the neurological scores (r=-0.68,
      P=0.01). Immunohistochemistry detected the presence of Foxp3 primarily in the
      ischemic region of the brain tissue 1 day after cerebral ischemia; the
      contralateral hemisphere also showed a small quantity of Foxp3 expression. No
      Foxp3 expression was detected in the brain tissue of the sham-operated group.
      CONCLUSION: CD4(+)CD25 T regulatory cells participate in the inflammatory immune
      reactions as early as 1 day after acute cerebral ischemia in rats, which might be
      a protective mechanism of the brain cells.

PMID- 22588920
TI  - [Comparison of long-term oncological outcomes of laparoscopic and open resection
      of rectal cancer].
AB  - OBJECTIVE: To compare the long-term oncological outcomes of laparoscopic and open
      resection of rectal cancers. METHODS: Between January, 2003 and December, 2008,
      514 patients with rectal cancer were admitted in our hospital, among whom 186
      underwent laparoscopic tumor resection and 238 received open radical resection of
      the tumors. The long-term survival of the patients and the recurrence pattern
      were compared between the two groups. RESULTS: The median follow-up of the
      patients was 48.54?28.76 months. No significant differences were found between
      the two groups in the local recurrence rate (3.9% vs 5.5%, P=0.284), 5-year
      overall survival (69.4% vs 61.3%, P=0.067), or the 5-year disease-free survival
      rates (67.7% vs 60.7%, P=0.110). Both the 5-year overall survival and progression
      free survival of the patients in stage IV were better in the laparoscopic group
      than in the open surgery group (P<0.05). CONCLUSION: Laparoscopic resection of
      rectal cancer can achieve long-term oncological outcomes comparable to those of
      conventional open surgery.

PMID- 22588921
TI  - [Common mutations of congenital adrenal hyperplasia are also the hotspots for new
      mutations].
AB  - OBJECTIVE: To discuss the genetic diagnosis of congenital adrenal hyperplasia
      (CAH) and investigate the resource of gene mutations in CAH. METHOD: Enzymatic
      methods with restriction endonucleases that specifically recognized the mutation
      sites were used to detect the gene mutations in patients with CAH and their
      relatives. Polymerase chain reaction and direct sequencing were used to identify
      the mutations in 21-hydroxylase gene, and short tandem repeat (STR) typing was
      used to determine the sources of the mutations. RESULTS: One CAH patient had two
      known mutations in 21-hydroxylase gene, namely the I2g and I172N mutations. The
      former mutation was inherited from the biological mother and the latter was not
      inherited. CONCLUSION: The 9 common mutations of CAH are also the hotspots for
      new mutations.

PMID- 22588922
TI  - [Determination of isoniazide concentration in pleural effusion and its pleural
      permeability in patients with tuberculous pleurisy].
AB  - OBJECTIVE: To establish a high-performance liquid chromatography (HPLC)-based
      method for determining isoniazide concentration in pleural effusion and plasma of
      patients with tuberculous pleurisy, and evaluate the permeability of isoniazide
      from blood into pleural effusion. METHODS: We collected pleural effusion from 15
      patients with tuberculous pleurisy 2 h after administration 300 mg isoniazide in
      the morning of day 1. Pleural effusion and plasma were obtained 2 h after
      isoniazide administration on day 3. Isoniazide concentration was measured using
      HPLC, and the penetration rate of isoniazide in pleural effusion was calculated.
      RESULTS: Isoniazide concentration in the pleural effusion averaged 1.156?1.190
      ug/ml in the 15 patients at 2 h after isoniazide administration on day 1. On day
      3, isoniazide concentration was 1.920?1.294 ug/ml in the pleural effusion and
      2.445?1.463 ug/ml in the plasma, and the mean penetration rate of isoniazide from
      blood into the pleural effusion was 86.0%. CONCLUSION: As isoniazide has a high
      penetration rate into the pleural effusion in most patients, continuous oral
      administration of isoniazid has been sufficient to achieve an effective treatment
      concentration, and intrapleural injection of isoniazide may seem unnecessary for
      non-drug-resistant tuberculosis pleurisy.

PMID- 22588923
TI  - [Effect of ischemic postconditioning on phosphatidylinositol-3-OH kinase and
      extracellular signal-regulated protein kinase in rats with hepatic ischemia
      reperfusion injury].
AB  - OBJECTIVE: To observe the effect of ischemic postconditioning on
      phosphatidylinositol-3-OH kinase (PI3K) and extracellular signal-regulated
      protein kinase 1/2(ERK1/2) in rats after hepatic ischemia reperfusion in rats and
      investigate the mechanism of ischemic postcoditioning of the liver. METHODS:
      Three cycles of 1 min-off-1 min-on ischemic postconditioning regime were used in
      a rat model of 70% hepatic ischemia-reperfusion injury. The changes in the liver
      function, hepatocyte apoptosis, phosphorylation of Akt and ERK1/2 were assessed
      in rats treated with sham operation, LY294002+sham operation (LY+S), PD98059+sham
      operation (PD+S), ischemia reperfusion (IR), ischemic postconditioning (IPO),
      LY294002+ ischemic postconditioning (LY+IPO), or PD98059+ischemic
      postconditioning (PD+IPO). RESULTS: Ischemic postconditioning significantly
      alleviated hepatic ischemia-reperfusion-induced liver function injury and
      hepatocyte apoptosis and increased phosphorylation of Akt and ERK1/2. LY294002
      and PD98059 antagonized the effects of ischemic postconditioning in the liver.
      CONCLUSION: Activation of PI3K and ERK1/2 may mediate the protective effect of
      ischemic postconditioning against hepatic ischemia- reperfusion injury in rats.

PMID- 22588924
TI  - [Influence of alkaline environment on the hydrophobicity of starved Enterococcus
      faecalis].
AB  - OBJECTIVE: To study the effect of calcium hydroxide solutions at different pH
      values on the cell-surface hydrophobicity of starved Enterococcus faecalis.
      METHODS: E. faecalis in starvation were harvested and incubated in freshly
      prepared calcium hydroxide solutions at the pH values ranging from 7.3 to 10.3
      for 15 min or 60 min. The cell-surface hydrophobicity of the starved E. faecalis
      was evaluated by measuring microbial adhesion to hydrocarbons (MATH). Scanning
      electron microscopy was used to investigate the adhesion capability of starved E.
      faecalis cells incubated on human dentin at different pH levels. RESULTS: For the
      same duration of treatment, increased pH value of calcium hydroxide solution
      significantly enhanced the cell-surface hydrophobicity of starved E. faecalis
      (P<0.01). At the same pH value, the cell-surface hydrophobicity of the bacterium
      increased significantly with time (P<0.05, 15 min vs 60 min). Scanning electron
      microscopy revealed a significantly increased adhesion of the starved cells on
      human dentin as the pH value and incubation time increased. CONCLUSION: Calcium
      hydroxide solutions promote the adhesion of starved E. faecalis by modifying its
      cell-surface hydrophobicity.

PMID- 22588925
TI  - [Clinical analysis of 15 cases of pseudohypoparathyroidism].
AB  - OBJECTIVE: To analyze the clinical characteristics, diagnosis and treatment of
      pseudohypoparathyroidism (PHP). METHODS: The clinical data of 15 patients with
      pseudohypoparathyroidism (including 9 male and 6 female patients) admitted in our
      hospital between January, 1990 and July, 2011 were reviewed. RESULTS: The disease
      course of the patients ranged from 3 days to 21 years, and such symptoms of
      tetany and fatigue were found in all the patients. Most of the patients had a
      history of seizures. Laboratory tests suggested commonly low serum calcium,
      hyperphosphatemia, and parathyroid hormone (PTH) elevation. Head CT indicated
      multiple intracranial calcifications in 9 cases, and abnormal thyroid function
      was found in 4 cases. No specific treatment was available for this disease, and
      life-long calcium and vitamin D supplementation was advised to prevent acute
      attacks and disease progression. CONCLUSION: PHP is a rare genetic disease with a
      high rate of misdiagnosis in initial diagnosis. For repeated tetany and epileptic
      attacks and children with congenital developmental defects, examinations of blood
      calcium, phosphorus, and PTH and brain CT should be ordered as soon as possible.
      Long-term calcium and vitamin D supplementation is suggested for the treatment,
      and the presence of concomitant thyroid dysfunction or hypogonadism necessitates
      corresponding treatments.

PMID- 22588926
TI  - [Effect of cervical conization through hysteroscopy for cervical intraepithelial
      neoplasia III].
AB  - OBJECTIVE: To evaluate the therapeutic effect of cervical conization through
      hysteroscopy in the treatment of cervical intraepithelial neoplasia (CIN) III.
      METHODS: Seventy-four patients with CIN III underwent cervical conization through
      hysteroscopy (TCRC group), and 65 received cold knife conization (CKC group). The
      operating time, volume of blood loss, concordance rate with pathology, recurrence
      rate, rate of cervix adhesion and pregnancy rate were compared between the two
      groups. RESULTS: The operating time, mean blood loss, cure rate, and recurrence
      rate were 15.1?3.2 min, 12.5?1.8 ml, 94.6%, and 5.4% in TCRC group, respectively,
      as compared with those of 25.8?3.8 min, 21.6?2.4 ml, 81.5%, and 18.5% in CKC
      group, all showing significant differences between the two groups (P<0.05).
      CONCLUSION: Compared with CKC, TCRC has such advantages as less blood loss,
      shorter operating time, more accurate lesion localization, fewer complications,
      higher cure rate, and lower recurrence rate without significant adverse effect on
      pregnancy.

PMID- 22588927
TI  - [Pretreatment doses of antithymocyte globubin-fresenius for allogeneic
      hematopoietic stem cell transplantation for beta-thalassemia major].
AB  - OBJECTIVE: To investigate the effects of different doses of antithymocyte
      globubin-fresenius (ATG-F) for allogeneic hematopoietic stem cell transplantation
      (allo-HSCT) in patients with beta-thalassemia Major. METHODS: Sixty-four children
      with beta-thalassemia major undergoing allo-HSCT were divided into two equal
      groups to receive ATG-F pretreatments at high (30 mg/kg) or low (15 mg/kg) doses
      as part of the conditioning regimen including mainly cyclophosphamide, busulfan,
      fludarabine, and thiotepa. The outcomes of the patients were compared between the
      two groups. RESULTS: No obvious difference were noted in the time to leukocyte
      and platelet engraftment between the two groups. The incidence of grade II-IV
      acute graft-versus-host disease (aGVHD) appeared to be higher in the low-dose
      group than in the high-dose group (12.5% vs 9.4%). The incidence of grade III-IV
      aGVHD was also higher in the low dose group (12.5% vs 6.3%), but the difference
      was not statistically significant. Application of high-dose ATG-F was associated
      with a higher rate of probable and possible fungal infection (P<0.05).
      CONCLUSION: The two doses of ATG-F is feasible as a part of the conditioning
      regimen for allo-HSCT in children with beta-thalassemia major.

PMID- 22588928
TI  - [Efficacy of antioxidants in treatment of nonalcoholic fatty liver: a systematic
      review].
AB  - OBJECTIVE: To evaluate the efficacy of antioxidants in the treatment of non
      alcoholic fatty liver. METHODS: The Cochrane Central Register of Controlled
      Trials (CENTRAL), MEDLINE or PUBMED (1978-2011), EMBASE (1978-2011), ISI, OVID
      Database (1978-2011), CNKI Net and WANFANG database (1978-2011) were searched for
      relevant randomized controlled trials, with also manual search of the
      bibliographies of the retrieved articles. The data were synthesized to assess the
      histological response of the patients (hepatic steatosis, inflammation and
      fibrosis) and hepatic biochemical changes after the treatments (alanine
      aminotransferase responses). RESULTS: Fourteen trials involving 1284 patients
      were included in the Meta-analysis. The quality of the trials was inconsistent.
      The data were extracted for meta-analysis or descriptive analysis, which did not
      yield sufficient evidence that antioxidants could improve hepatic steatosis,
      inflammation, fibrosis or alanine aminotransferase responses. CONCLUSIONS: The
      current data do not support a positive therapeutic effect of antioxidants on
      nonalcoholic fatty liver, and antioxidants are therefore not recommended in the
      clinical treatment of the condition.

PMID- 22588929
TI  - [Topical application of leptin promotes burn wound healing in rats].
AB  - OBJECTIVE: To investigate the effect of topical application of leptin in
      promoting burn wound healing in rats. METHODS: Four parallel second-degree burn
      wounds induced on the back of 18 Wistar rats were divided into leptin treatment
      group (treated with topical application of 400 ng/ml leptin dissolved in PBS) and
      control group (treated with PBS). The time of wound healing was recorded, and the
      wound area that was not healed was measured at 3, 7, 11, 15, and 19 days after
      burns. The tissue at the peripheries of the wound was sampled at 7, 14 and 21
      days after burns for pathological examination with HE staining and
      immunohistochemistry for proliferating cell nuclear antigen (PCNA) to evaluate
      the proliferation of keratinocytes. RESULTS: Compared with the control group,
      leptin-treated wounds showed a shorter time (by 2-3 days) of wound healing, and
      significant differences were found between the two groups in healing at 7, 11,
      15, and 19 days after burns. HE staining and immunohistochemistry revealed a
      faster rate of epidermis growth and a greater thickness of the cuticular layer in
      leptin-treated wounds at 7, 14 and 21 days after burns. PCNA positivity in the
      keratinocytes was stronger in leptin-treated wounds than in the control wounds at
      7 and 14 days, but no such distinct difference was noted at 21 days between the
      two groups. CONCLUSION: Topical application of leptin can promote re
      epithelization in burn wounds to shorten the wound healing time of burns.

PMID- 22588930
TI  - [Cytogenetic differences between adults and children with acute lymphoblastic
      leukemia: eight-probe fluorescence in situ hybridization and karyotype analyses].
AB  - OBJECTIVE: To investigate the cytogenetic differences between children and adults
      with acute lymphoblastic leukemia (ALL) using eight-probe fluorescence in situ
      hybridization and karyotype analysis. METHODS: Eight-probe (MYC, P16, E2A,
      TEL/AML1, BCR/ABL , MLL , IGH, and hyperdiploidy) fluorescence in situ
      hybridization and karyotype analysis were performed for  86 adults and 39
      children with acute lymphoblastic leukemia. RESULTS: Eight-probe fluorescence in
      situ hybridization showed significant differences in the positivity rate of
      TEL/AML1, BCR/ABL, and hyperdiploidy between adult patients and children with
      ALL. By karyotype analysis, the positivity rate of t(9;22) and hyperdiploidy
      differed significantly between the children and adult patients (P<0.05).
      CONCLUSION: Adults and children with ALL have different expression profiles of
      the fusion genes. Eight-probe fluorescence in situ hybridization is time-saving,
      accurate and efficient in detecting common genetic abnormalities in ALL patients,
      and can be well complementary to karyotype analysis in clinical diagnosis of ALL.

PMID- 22588931
TI  - [Effects of 1,25(OH)(2)D(3) on SGC-7901 cell proliferation and tumor necrosis
      factor-alpha expression].
AB  - OBJECTIVE: To investigate the effect of 1,25 (OH)(2)D(3) on cell proliferation
      and the expression of tumor necrosis factor-alpha  (TNF-alpha ) in human gastric
      carcinoma SGC-7901 cells. METHODS: SGC-7901 cells were treated with 1*10(-6),
      1*10(-7), 1*10(-8), and 1*10(-9) mol/L 1,25 (OH)(2)D(3) for 24, 48, 72 and 96 h.
      The cell proliferation was measured by MTT assay, and the cell cycle changes were
      analyzed using flow cytometry. RT-PCR and Western blotting were used to determine
      the expression of TNF-alpha mRNA and protein, respectively. RESULTS: 1,25
      (OH)(2)D(3) significantly inhibited SGC-7901 cell proliferation (P<0.05) in a
      time- and dose-dependent fashion. Treatment with 1,25 (OH)(2)D(3) for 72 h caused
      significant cell cycle arrest at G(0)/G(1) phase  (F=9.81, P<0.05) and dose
      dependently inhibited the expression of TNF-alpha at both mRNA and protein levels
      in SGC-7901 cells (P<0.05). CONCLUSION: The inhibitory effect of 1,25 (OH)(2)D(3)
      on SGC-7901 cell proliferation is probably associated with the down- regulation
      of TNF-alpha expression.

PMID- 22588932
TI  - [Role of C5b-9 expression in skeletal muscle blood vessels in necrotizing
      myopathy].
AB  - OBJECTIVE: To investigate the expression of C5b-9 in the skeletal muscle blood
      vessels in patients with necrotizing myopathy and explore its role in the
      pathogenesis of this disease. METHODS: The expression of C5b-9 and MHC-I in the
      skeletal muscular fibers and blood vessels in 4 patients with necrotizing
      myopathy was detected using enzymohistochemistry and immunohistochemistry.
      RESULTS: Focal or dispersive necrotic muscle fibers with obvious phagocytosis
      were observed in all the 4 patients. No inflammatory cell infiltration was found
      in the perimysium or perivascular regions. HE staining showed a decreased number
      of local small blood vessels, and the some small blood vessels showed thickened
      vascular walls. Immunohistochemistry detected prominent C5b-9 expression in the
      necrotic muscle fibers and the blood vessels, and diffuse strong C5b-9 expression
      was found in the vascular walls, vascular endothelial cells and the smooth muscle
      layer. No MHC-I deposition was detected in the muscular fibers and blood vessels.
      CONCLUSION: C5b-9 contributes to the pathogenesis of necrotizing myopathy
      mediated by pathologies in the blood vessels.

PMID- 22588933
TI  - [Effect of polyethylene oxide on renal hemodynamics in rabbits with endotoxin
      shock].
AB  - OBJECTIVE: To investigate the effect of polyethylene oxide (PEO) on renal blood
      flow and its renoprotective effect in rabbits with endotoxin sepsis. METHODS:
      Twenty normal New Zealand white rabbits were randomly divided into normal saline
      (NS) group and PEO group (n=10), and endotoxin shock was induced by an
      intravenous injection of 0.6 mg/kg lipopolysaccharide. Resuscitation was
      performed when the blood pressure of the rabbits showed a 30% decline, using NS
      (in NS group) or the mixture of equal volumes of NS and  20 ng/g PEO (in PEO
      group) perfused at the rate of 5 ml/kg per hour. Before and during shock and at 1
      h after resuscitation, the renal hemodynamics was monitored by ultrasound and the
      venous blood was extracted to examine the renal functions. The heart rate and
      arterial blood pressure were monitored throughout the experiment. RESULTS: The
      rabbits in both groups showed a significantly lower renal artery blood flow
      velocity during the shock (P<0.05) with significantly increased pulsatility index
      (PI) and resistance index (RI) compared with those before the shock. One hour
      after resuscitation, the blood flow velocity in the renal arteries at all levels
      and the tertiary veins were reduced in NS group without obvious reduction of the
      PI and RI; in PEO group, the blood flow velocities in the renal arteries
      increased significantly compared to those before shock (P<0.05), and the PI and
      RI of the tertiary arteries were significantly lower than those in NS group
      (P<0.05). In both groups, BUN and Cr increased during endotoxin shock stage, and
      1 h after resuscitation, PEO group showed significantly lower BUN and Cr levels
      than NS group (P<0.05). CONCLUSION: A small dose of PEO can significantly promote
      renal perfusion in rabbits with septic shock, thus offering renoprotective effect
      against early damage in septicopyemia and septic shock.

PMID- 22588934
TI  - [Effects of curcumin on syndecan-4 protein and p44/42 mitogen-activated protein
      kinase expression in tumor necrosis factor-alpha-induced rat vascular smooth
      muscle cells in vitro].
AB  - OBJECTIVE: To investigate the effects of curcumin on the expression of syndecan-4
      protein and p44/42 mitogen- activated protein kinase(MAPK) phosphorylation in rat
      vascular smooth muscle cells (VSMCs) induced by tumor necrosis factor-alpha (TNF
      alpha) in vitro. METHODS: Rat VSMCs cultured in vitro were stimulated for 24 h by
      20 ng/ml TNF-alpha, 20 umol/L curcumin, or 20 ng/ml TNF-alpha plus 20 umol/lL
      curcumin. /assay was adopted to evaluate the proliferation of the VSMCs, and the
      expression of syndecan-4 protein and phosphorylated p44/42 MAPK were determined
      by Western blotting. RESULTS: Compared with the normal control cells, VSMCs
      exposed to TNF-alpha showed significantly enhanced proliferation (P/0.01).
      Curcumin treatment did not obviously affect the growth of otherwise untreated
      VSMCs(P>0.05), but could significantly suppress TNF-alpha-induced proliferation
      of VSMCs (P/0.01). TNF-alpha treatment also significantly increased the
      expression of syndecan-4 protein and phosphorylated p44/42 MAPK (P<0.01), which
      was markedly lowered by treatment with curcumin (P/0.01). Curcumin alone did not
      produce any obvious effects on the expression of syndecan-4 protein or
      phosphorylated p44/42 MAPK (P>0.05). CONCLUSION: Curcumin can suppress the
      proliferation of rat VSMCs and lower the expression of syndecan-4 protein and
      phosphorylated p44/42 MAPK in TNF-alpha-induced VSMCs.

PMID- 22588935
TI  - [Hepatic SIRT1 and UCP2 expressions in rats with type 2 diabetes mellitus and
      nonalcoholic fatty liver].
AB  - OBJECTIVE: To observe the expression of SIRT1 and mitochondrial uncoupling
      protein 2 (UCP2) in the liver of rats with type 2 diabetes mellitus (T2DM) and
      nonalcoholic fatty liver (NAFLD) and explore the possible pathogenesis of T2DM
      and NAFLD. METHODS: Twenty-four male SD rat were randomized equally into control
      group and T2DM and NAFLD group (MC group), fed with standard diet and high-fat
      and high-sugar diet, respectively. At 12 weeks, the rats in MC group received a
      single dose of STZ (30 mg/kg) injected into the abdominal cavity for pancreatic
      islet destruction, and those in the control group received an equivalent volume
      of citric acid buffer. At 14 weeks, the body weight, FBG, hepatic function, blood
      lipid levels, FFAs, FINs and HOMA-IR of the rats were measured, and the liver
      pathology was examined with HE staining. The expression of SIRT1 and UCP2 in the
      rat liver was detected by immunohistochemistry and real-time quantitative PCR.
      RESULTS: At 14 weeks, FBG, ALT, AST, TC, TG, LDL-C, VLDL, FFAs, FINs and HOMA-IR
      were significantly higher and HDL-C was significantly lower in MC group than in
      the control group (P<0.05). Pathological examination showed good structural
      integrity of the liver in the control group, and the liver cells were closely
      arranged with rich cytoplasm and round cell nuclei; in MC group, moderate to
      severe fatty liver was detected, and the liver cells showed severe ballooning
      degeneration and contained lipid vacuoles in the cytoplasm. The expression of
      SIRT1 was significantly lower and UCP2 significantly higher in MC group than in
      the control group (P<0.05). CONCLUSION: The expression of SIRT1 is significantly
      lowered and UCP2 increased in the liver of rats with T2DM and NAFLD.

PMID- 22588936
TI  - [Low frequency ultrasound promotes lactation in lactating rats].
AB  - OBJECTIVE: To investigate the effect of low-frequency ultrasound in promoting
      milk secretion in rats during lactation. METHODS: Twenty-four lactating SD rats
      feeding 10 suckling rats each were randomly allocated into 3 groups, namely the
      control group (with sham irradiation), 5 min group (with ultrasonic irradiation
      of the breast for 5 min daily), and 10 min group (irradiation for 10 min daily).
      The mammary glands of the rats were consistently irradiated by low-frequency
      ultrasound (40 kHz, 0.26 W/cm(2)) for 7 days since the 2nd day after delivery.
      The milk yield, average body weight gain of the offspring, mammary gland index,
      serum prolactin (PRL) and breast histology were examined. RESULTS: The milk
      yield, body weight gain of offspring, mammary gland index and serum PRL
      concentration in 10 min group were significantly greater than those in the
      control group and 5 min group (P<0.05). Compared with the other two groups, the
      10 min group showed significantly increased acinar gland expansion and acinar
      number. CONCLUSION: Low-frequency ultrasound can promote milk secretion in
      lactating rats, suggesting its potential as a new approach of physical therapy
      for promoting milk secretion.

PMID- 22588937
TI  - [Adenosine alleviates hypoxia-induced rat right ventricular hypertrophy through
      the NHE-1/CaN signal pathway].
AB  - OBJECTIVE: To investigate the effect of adenosine and its agonist on hypoxia
      induced right ventricular hypertrophy (RVH) and explore the underlying mechanism.
      METHODS: Fifty-six rats were randomly divided into normoxia group, hypoxia group,
      and treated hypoxia groups (with different treatments with adenosine, A1 receptor
      agonist CPA, A2 receptor agonist NECA, CPA plus A1 receptor inhibitor DPCPX, or
      NECA plus A2B receptor inhibitor MRS1754). The rats except for those in normoxia
      group were exposed to normobaric chronic hypoxia (9.5%-10.5% oxygen) for 21 days,
      and the corresponding treatments were administered since the 7th day of hypoxia
      till day 21 via implantable capsule with a pressure pump. After the treatments,
      the right ventricles were then removed and weighed for evaluation of hypertrophy,
      and the expressions of NHE-1 and CnAbeta mRNA in the myocardial tissue were
      detected using RT-PCR. RESULTS: After a 21-day hypoxia, the rats showed
      significantly increased RV/(LV+S) ratio (0.369?0.033) and RV/BW ratio
      (0.75?0.095) compared to those in normoxia group (0.271?0.010 and 0.59?0.039,
      respectively; P<0.001), adenosine treatment group (0.281?0.022 and 0.65?0.077,
      respectively; P<0.001, P=0.025), hypoxia with CPA group (0.313?0.021 and
      0.66?0.067, respectively P<0.001), and hypoxia with NECA group(0.333?0.019, and
      0.68?0.074, respectively P<0.001). The NHE-1 and CnAbeta mRNA levels in hypoxia
      group were significantly higher than those in normoxia group, adenosine treatment
      group, hypoxia with CPA group, and hypoxia with NECA group(P<0.001). CONCLUSION:
      Adenosine and its agonist can inhibit hypoxia-induced RVH in rats through the NHE
      1/CaN signal pathway.

PMID- 22588938
TI  - [Investigation of enterotoxin gene in clinical isolates of Staphylococcus
      aureus].
AB  - OBJECTIVE: To detect the enterotoxin genes of Staphylococcus aureus (SA) isolated
      from clinical specimens and analyze the correlation between enterotoxin genes and
      drug resistance of SA. METHODS: The mecA gene and enterotoxin genes A-F of
      clinical SA isolates were identified by polymerase chain reaction (PCR), and the
      genes were sequenced to investigate the correlation of these genes to drug
      resistance. RESULTS: The detection rate of enterotoxin genes was 100% in 67
      methicillin- resistant SA (MRSA), showing no significant difference from the rate
      in 57 methicillin-sensitive SA (MSSA) (83.5%, chi(2)=0.203, P>0.05). Of the 116
      strains carrying enterotoxin genes (93.5%), the detection rates of SEA, SEB, SEC,
      SED and SEF were 90.5%, 6.9%, 61.3%, 5.2%, 25.9% and 93.5%, respectively, and
      none of the strains were positive for SEE gene. In these strains, 78 (67.2%)
      carried 2 or more enterotoxin genes, and the main genotypes were SEA and SEC
      (33.6%), SEA and SEF (7.8%), and SEA and SEC and SEF (13.8%). Compared with the
      strains carrying a single enterotoxin gene, those with multiple enterotoxin genes
      showed a higher drug resistance rate, among which 75% of the SA strains carrying
      SEA+SEC+SEF were resistant to SXT, significantly higher than the rates of SA
      carrying SEA (28.6%) and SEA+SEC (38.7%) (P<0.05). The SA strains carrying
      SEA+SEC+SEF and SEA+SEF showed significantly higher amikacin resistance rates
      than SA strain carrying SEA (75.0%, 77.0%, 21.5%, respectively, P<0.05).
      CONCLUSION: Clinical isolates of SA carrying multiple enterotoxin genes have a
      higher drug resistance rate than those with a single enterotoxin gene, suggesting
      the the important role of enterotoxin in multidrug resistance.

PMID- 22588939
TI  - [Preparation of a monoclonal antibody against fusion protein preM/EIII of WNV].
AB  - OBJECTIVE: To prepare a monoclonal antibody (mAb) against the fusion protein
      preM/EIII of West Nile virus (WNV) for clinical detection of WNV. METHODS: Sp2/0
      cells were fused with the spleen cells of BALB/c mice immunized with the
      recombinant fusion protein preM/EIII expressed in E. coil to obtain the hybridoma
      cell line that secreted preM/EIII mAb. The hybridoma cells were injected into the
      peritoneal cavity of BALB/c mice and the ascites was collected and purified. The
      specificity and titer of the obtained mAb were determined using ELISA and Western
      blotting. RESULTS: One hybridoma cell line secreting preM/EIII mAb, named ME1,
      was obtained. The titer of the purified mAb was 10(-6). Identified as a mAb of
      the Ig subclass IgG1, ME1 was capable of specific reactions with preM/EIII
      protein and WNV without cross-reactions with other viruses such as JEV, SLEV, YFV
      and DENV. The accuracy of clinical testing of MNV with ME1 was 97.78%.
      CONCLUSION: The mAb against preM/EIII obtained have a high specificity and
      accuracy in clinical testing of MNV and can be used in clinical diagnosis of MNV
      infection.

PMID- 22588940
TI  - [Influence of background color on four veneered dental ceramic core material].
AB  - OBJECTIVE: To investigate the influence of background color on veneered In-Ceram
      and Cercon dental ceramics including Vita In-Ceram Electroformed Alumina (AL2),
      Electroformed Zirconia (Z21), Cercon base color Zirconia and Cercon base
      Zirconia. METHODS: The colorimetric values of all the materials on noble metal,
      Ni-Cr alloy, silver amalgam and resin background were measured with a
      spectrocolorimeter, and the color difference among the groups was calculated.
      RESULTS: After veneered, the color difference of Z21 Electroformed Zirconia was
      more distinct against the background of silver amalgam than against the
      backgrounds of noble metal and resin, but the color differences of the 4 veneered
      dental ceramics against different backgrounds were unidentifiable by human eyes
      (deltaE<1.5). CONCLUSION: After veneered, AL2 electroformed alumina, Z21
      electroformed zirconia, Cercon base Zirconia and Cercon base color Zirconia are
      less influenced by the background color, and covering the background color is
      therefore not necessary.

PMID- 22588941
TI  - [Extraperitoneal robot-assisted laparoscopic radical prostatectomy: report of 20
      cases].
AB  - OBJECTIVE: To summarize our experience with extraperitoneal robot-assisted
      laparoscopic radical prostatectomy (RLRP). METHODS: Twenty patients with
      confirmed prostate cancer by transrectal needle biopsy but no metastasis detected
      by radiographic examination underwent extraperitoneal RLRP, including 7 with
      Gleason score of less than 6, 10 with a score of 7, 2 with a score of 8, and 1
      with a score of 9. RESULTS: The procedures were performed successfully in all the
      patients. In 4 cases, a postoperative PSA value of more than 0.2 ng/ml at 4 weeks
      suggested residual tumor, for which maximal androgen block therapy was
      administered before elective radiotherapy. Sixteen patients were followed up for
      10 to 37 months (mean 15.5 months). In the 20 cases, the operation was completed
      in a mean of 180 min (range 150-230 min), with the mean installation time of 48.5
      min (range 40-60 min) and average blood loss of 298 ml (range 80-800 ml). The
      mean postoperative eating time was 1.7 days (1 to 3 days), the mean bladder
      catheter time was 10.7 days (7 to 14 days), and the mean hospital stay was 10.7
      days (range 7-14 days). No postoperative complications occurred in these cases.
      Postoperative pathology showed a Gleason score no higher than 6 in 6 cases, 7 in
      5 cases, and no less than 8 in 9 cases. CONCLUSION: The technique of
      extraperitoneal RLRP can be easily mastered by the surgeons and is especially
      advantageous for complicated pelvic operations.

PMID- 22588942
TI  - [Clinical significance of detecting peripheral blood T lymphocyte subsets in
      patients with pulmonary adenocarcinoma].
AB  - OBJECTIVE: To evaluate the clinical value of T lymphocyte subsets in prediction
      of chemotherapy responses of patients with pulmonary adenocarcinoma. METHODS:
      Fifty-five chemotherapy-naive patients with pathologically or cytologically
      confirmed pulmonary adenocarcinoma were examined for peripheral blood T
      lymphocyte subsets using flow cytometry, including CD3(+) T cells, CD3(+)CD4(+) T
      cells, CD3(+)CD8(+) T cells, CD45RO(+) T cells and CD45RA(+) T cells. RESULTS:
      Patients who responded favorably to chemotherapy (CR(+)PR) showed a significantly
      lower percentage of CD45RA(+) T cells than those who failed to respond to
      chemotherapy (P=0.04). CD45RO(+) T cell percentage were slightly higher in the
      response group than in the non-response group, but this difference was not
      statistically significant (P=0.25). The other T cell subsets, namely CD3(+),
      CD3(+)CD4(+), and CD3(+)CD8(+) T cells showed no significant differences between
      the two groups. CONCLUSION: A high percentage of peripheral blood CD45RA(+) T
      cells is associated with a poor short-term outcome of chemotherapy in patients
      with advanced pulmonary adenocarcinoma. Peripheral blood CD45RA(+) T cell level
      can be a reliable index for predicting chemotherapy efficacy in these patients.

PMID- 22588943
TI  - Treatment and outcomes of acute coronary syndrome in the cancer population.
AB  - BACKGROUND: Randomized trials have established the benefit of medical therapy and
      revascularization in the treatment of acute myocardial infarction (MI). Cancer
      and cardiovascular disease are the 2 most common diseases worldwide. In clinical
      practice, cancer patients are frequently afflicted with MI. The benefit of
      medical and/or revascularization therapy in the cancer population with MI is less
      well known. HYPOTHESIS: Medical and revascularization therapy reduces mortality
      in cancer patients with MI. METHODS: After approval by the institutional review
      board, we retrospectively reviewed all patients with a discharge diagnosis of
      acute MI who were admitted to the University of Texas MD Anderson Cancer Center
      between December 2000 and October 2006 and evaluated the association between
      cardiac treatments with survival outcomes. RESULTS: A total of 456 patients with
      a discharge diagnosis of acute MI were identified and included in the study, of
      which 386 had non-ST-segment elevation MI (NSTEMI) and 70 had ST-segment
      elevation MI (STEMI). Compared with patients with NSTEMI, patients who had STEMI
      were more often prescribed aspirin (66% vs 43%; P = 0.004), beta-blockers (61% vs
      46%; P = 0.018), and thrombolytic therapy (9% vs 0.3%; P = 0.0001). In the
      multivariable analysis, aspirin use was associated with a 23% decreased risk of
      death (hazard ratio [HR]: 0.77, 95% confidence interval [CI]: 0.60-0.98, P =
      0.033) and beta-blocker use was associated with a 36% decreased risk of death
      (HR: 0.64, 95% CI: 0.51-0.81, P = 0.0002). Statins (HR: 0.82, P = 0.18) and
      catheter-based revascularization (HR: 0.57, P = 0.09) did not have an impact on
      the risk of death. Compared with patients with limited cancer, advanced cancer
      patients were twice as likely to die (HR: 2.12, 95 CI: 1.47-3.04, P < 0.0001).
      Previous chemotherapy (P = 0.005) and chest radiotherapy (P = 0.017) were
      associated with increased 1-year mortality, whereas hyperlipidemia (P = 0.018)
      was protective. CONCLUSIONS: In this study of cancer patients with MI, medical
      therapy with aspirin and beta-blockers was associated with improved survival. The
      authors have no funding, financial relationships, or conflicts of interest to
      disclose.

PMID- 22588944
TI  - Synthesis of 3,4-dihalogenated furan-2-(5H)-ones by electrophilic cyclization of
      4-hydroxy-2-alkynoates.
AB  - Functionalized 3,4-dihalogenated furan-2(5H)-ones can be readily prepared in
      moderate to good yields by treating 4-hydroxy-4-arylbut-2-ynoate derivatives with
      ICl, IBr, and I(2). Both halogen atoms of the electrophile are incorporated in
      the product. The resulting halides can further afford polycyclic aromatic
      compounds using known palladium-catalyzed coupling reactions.

PMID- 22588946
TI  - Cognitive deficit in first-time coronary artery bypass graft patients: a
      randomized clinical trial of lidocaine versus procaine hydrochloride.
AB  - INTRODUCTION: Cognitive dysfunction increasingly has been recognized as a
      complication after cardiac surgery. Different methods have been considered for
      the reduction of cognitive dysfunction after cardiac surgery. One of these
      methods is by using lidocaine during surgery. The aim of this study was to
      determine the effects of adding lidocaine to the cardioplegia solution on
      cognitive impairment after coronary artery surgery. DESIGN AND METHODS: In a
      prospective, randomized, double-blind trial, 110 patients aged between 20-70
      years, scheduled for elective CABG surgery using cardiopulmonary bypass, were
      recruited into the study. They were randomized into two groups who received
      either cardioplegia solution containing lidocaine 2 mg/kg or procaine
      hydrochloride 5 mg/kg. The neurocognitive test used in this study was the Mini
      Mental State Examination (MMSE) or Folstein test. The test was done on the day
      before and 10 days and 2 months after the operation. RESULTS: In the procaine
      group, the total score after 10 days decreased significantly compared to the
      preoperative score (mean difference 0.68; 95% CI: 0.20 to 1.17, p=0.006).
      Comparison between mean differences after 10 and 60 days of operation between the
      lidocaine and procaine groups were statistically significant, p-value 0.017 and
      0.013, respectively. There was no cognitive impairment in the lidocaine group,
      but, in the procaine group, four patients (7.7%) after 10 days and one patient
      (1.9%) after both 10 and 60 days had cognitive impairment, p=0.051. CONCLUSIONS:
      Administration of lidocaine compared to that of procaine through the cardioplegia
      solution had a better effect on cognitive function after coronary artery bypass
      graft surgery.

PMID- 22588945
TI  - Childhood respiratory symptoms and mental health problems: the role of
      intergenerational smoking.
AB  - OBJECTIVE: The aim of this study was to investigate the potential role of youth
      smoking, parental cigarette smoking and parental anxiety/depressive disorders in
      the relationship between respiratory symptoms and mental health problems among
      youth. WORKING HYPOTHESIS: Adjusting for both parental smoking and parental
      anxiety/depressive disorders in the association between respiratory symptoms and
      mental health problems among young persons will significantly reduce the strength
      of the observed relationship. STUDY DESIGN: Prospective cohort study. PATIENT
      SUBJECT SELECTION: Data were drawn from a school-based sample of 1709 young
      persons in Oregon. METHODOLOGY: Physical and mental health data were collected on
      youth. RESULTS: Respiratory symptoms were associated with significantly increased
      odds of mental health problems among youth. After adjusting for youth smoking,
      the relationship between respiratory symptoms and depressive disorders was no
      longer statistically significant. The relationships between respiratory symptoms
      and anxiety and depressive disorders were no longer significant after adjusting
      for parental smoking. Parental anxiety/depressive disorders did not appear to
      influence these relationships. CONCLUSIONS: These results provide initial
      evidence that exposure to parental smoking may play a role in the observed co
      occurrence of respiratory and mental health problems in youth, and youths' own
      smoking appears to influence the link with depressive disorders, but not anxiety
      disorders.

PMID- 22588947
TI  - Functional organic materials based on polymerized liquid-crystal monomers:
      supramolecular hydrogen-bonded systems.
AB  - Functional organic materials are of great interest for a variety of applications.
      To obtain precise functional properties, well-defined hierarchically ordered
      supramolecular materials are crucial. The self-assembly of liquid crystals has
      proven to be an extremely useful tool in the development of well-defined
      nanostructured materials. We have chosen the illustrative example of
      photopolymerizable hydrogen-bonding mesogens to show that a wide variety of
      functional materials can be made from a relatively simple set of building blocks.
      Upon mixing these compounds with other reactive mesogens, nematic, chiral
      nematic, and smectic or columnar liquid-crystalline phases can be formed that can
      be applied as actuators, sensors and responsive reflectors, and nanoporous
      membranes, respectively.

PMID- 22588948
TI  - List-method directed forgetting: the forget cue improves both encoding and
      retrieval of postcue information.
AB  - In list-method directed forgetting, people are cued to forget a previously
      studied item list and to learn a new list instead. Such cuing typically leads to
      forgetting of the first list and to memory enhancement of the second, referred to
      as list 1 forgetting and list 2 enhancement. In the present study, two
      experiments are reported that examined influences of items' serial learning
      position in a list and the two lists' output order on list-method directed
      forgetting. The results show that list output order influences list 2 enhancement
      but not list 1 forgetting. The enhancement was higher when list 2 was recalled
      first than when list 1 was recalled first and, in both cases, was higher for
      early list 2 items than for middle and late list 2 items. In contrast, the
      forgetting was equally present for all list 1 items and did not depend on the two
      lists' output order. The findings suggest that two separate factors can
      contribute to list 2 enhancement: one (encoding) factor that is restricted to
      early list 2 items and does not depend on list output order, and another
      (retrieval) factor that pertains to all list 2 items and varies with the two
      lists' output order. A new two-mechanism account of directed forgetting is
      suggested that reconciles previous (encoding or retrieval) views on list 2
      enhancement.

PMID- 22588949
TI  - Dietary energy balance modulates epithelial-to-mesenchymal transition and tumor
      progression in murine claudin-low and basal-like mammary tumor models.
AB  - Using novel murine models of claudin-low and basal-like breast cancer, we tested
      the hypothesis that diet-induced obesity (DIO) and calorie restriction (CR)
      differentially modulate progression of these aggressive breast cancer subtypes.
      For model development, we characterized two cell lines, "mesenchymal (M)-Wnt" and
      "epithelial (E)-Wnt," derived from MMTV-Wnt-1 transgenic mouse mammary tumors. M
      Wnt, relative to E-Wnt, cells were tumor-initiating cell (TIC)-enriched (62% vs.
      2.4% CD44(high)/CD24(low)) and displayed enhanced ALDEFLUOR positivity,
      epithelial-to-mesenchymal transition (EMT) marker expression, mammosphere-forming
      ability, migration, invasion, and tumorigenicity (P < 0.001; each parameter). M
      Wnt and E-Wnt cells clustered with claudin-low and basal-like breast tumors,
      respectively, in gene expression profiles and recapitulated these tumors when
      orthotopically transplanted into ovariectomized C57BL/6 mice. To assess the
      effects of energy balance interventions on tumor progression and EMT, mice were
      administered DIO, control, or CR diets for 8 weeks before orthotopic
      transplantation of M-Wnt or E-Wnt cells (for each cell line, n = 20 mice per
      diet) and continued on their diets for 6 weeks while tumor growth was monitored.
      Relative to control, DIO enhanced M-Wnt (P = 0.01), but not E-Wnt, tumor
      progression; upregulated EMT- and TIC-associated markers including N
      cadherin,fibronectin, TGFbeta, Snail, FOXC2, and Oct4 (P < 0.05, each); and
      increased intratumoral adipocytes. Conversely, CR suppressed M-Wnt and E-Wnt
      tumor progression (P < 0.02, each) and inhibited EMT and intratumoral adipocyte
      accumulation. Thus, dietary energy balance interventions differentially modulate
      EMT and progression of claudin-low and basal-like tumors. EMT pathway components
      may represent targets for breaking the obesity-breast cancer link, particularly
      for preventing and/or controlling TIC-enriched subtypes such as claudin-low
      breast cancer.

PMID- 22588950
TI  - Urine concentrating and diluting ability during aging.
AB  - Urine concentrating ability is reduced during normal aging in people and rats.
      The abundance of many of the key transport proteins that contribute to urine
      concentrating ability is reduced in the kidney medulla of aged rats. The
      reductions in water, sodium, and urea transport protein abundances, and their
      reduced response to water restriction, contribute to the reduced ability of aged
      rats to concentrate their urine and conserve water. If similar mechanisms occur
      in human kidneys, it would provide a molecular explanation for the reduced urine
      concentrating ability in aging and may provide opportunities for novel
      therapeutic approaches to improve urine concentrating ability and/or nocturnal
      polyuria.

PMID- 22588951
TI  - Aldosterone-induced osteopontin expression in vascular smooth muscle cells
      involves MR, ERK, and p38 MAPK.
AB  - Osteopontin (OPN) is known to be one of the cytokines that is involved in the
      vascular inflammation caused by aldosterone (Ald). Previous reports have shown
      that Ald increases OPN expression, and the mechanisms for this remain to be
      clarified. In this study, we investigated how Ald increases OPN expression in the
      vascular smooth muscle cells (VSMCs) of rats. Ald increased OPN expression time
      dependently as well as dose dependently. This increase was diminished by
      spironolactone, a mineralocorticoid receptor (MR) antagonist. PD98059, an
      inhibitor of p42/44 MAPK pathway, and SB203580, an inhibitor of p38 MAPK pathway,
      suppressed Ald-induced OPN expression and secretion in VSMCs. VSMCs migration
      stimulated by aldosterone required OPN expression. In conclusion, these data
      suggest that Ald-induced OPN expression in VSMC is mediated by MR and signaling
      cascades involving ERK and p38 MAPK. These molecules may represent therapeutic
      targets for the prevention of pathological vascular remodeling.

PMID- 22588952
TI  - The study of soluble intercellular adhesion molecule-1 and ghrelin in adolescents
      with family history of type 2 diabetes.
AB  - The purpose of this study was to observe both the changes of soluble
      intercellular adhesion molecule-1 (sICAM-1) and ghrelin in adolescents with
      family history of type 2 diabetes (FHD) and the relationship between sICAM-1 and
      ghrelin. This case-control study included 63 adolescents (boys/girls 29/34, age
      14.1 +/- 0.7 years) without FHD (FHD-) and 67 adolescents (boys/girls 33/34, age
      14.0 +/- 0.8 years) with FHD (FHD+). Anthropometric measurements, including
      height, weight, waist circumference (WC), and blood pressure, were obtained.
      Blood samples were collected, and fasting plasma glucose (FPG), serum lipids,
      true insulin, sICAM-1, and ghrelin were assayed. The results showed that the age
      and gender were similar in two groups (P > 0.05). Body mass index (BMI), WC, FPG,
      fasting insulin, HOMA-IR, and sICAM-1 were all significantly higher in the FHD+
      group than in the FHD- group (P < 0.05). Ghrelin was significantly lower in the
      FHD+ group than in the FHD- group (P < 0.05). sICAM-1 was positively correlated
      with WC (r = 0.178, P = 0.043), fasting insulin (r = 0.195, P = 0.026), HOMA-IR
      (r = 0.197, P = 0.024), and ghrelin (r = 0.290, P = 0.001). After multivariate
      analysis, the ghrelin (beta = 0.788, 95 % CI: 0.416-1.159, P = 0.000) and HOMA-IR
      (beta = 0.106, 95 % CI: 0.045-0.167, P = 0.001) maintained an independent
      association with sICAM-1. These findings led to the conclusion that endothelial
      dysfunction and decline of ghrelin were found in adolescents with family history
      of diabetes. The decline of ghrelin maybe a protection mechanism for endothelial
      function in adolescents with family history of diabetes and should be examined in
      future studies.

PMID- 22588954
TI  - [The inseparable link between violence and psychiatry].

PMID- 22588953
TI  - Subclinical hypercortisolism: debatable or visible on the lightbox?

PMID- 22588955
TI  - [Frontotemporal dementia and schizophrenia in later life: a comparison of
      executive and general cognitive functioning].
AB  - BACKGROUND: Frontotemporal dementia (FTD) is characterised clinically by
      progressive changes in behaviour and personality; these changes are followed by
      cognitive disorder. FTD needs to be differentiated from other forms of dementia
      and from psychiatric conditions such as schizophrenia. Both FTD and schizophrenia
      lead to cognitive disorders and particularly to executive impairments. AIM: To
      compare executive and general cognitive functioning in patients with FTD and in
      patients with schizophrenia in later life. METHOD: As cognitive screening
      instruments we used the 'Frontal Assessment Battery' (FAB) and the 'Mini-Mental
      State Examination' (MMSE). The FAB en MMSE test results (retrieved from the
      database of the Alzheimer centre of the VU medical centre) for 25 outpatients
      diagnosed as having FTD were compared with the test results (retrieved from the
      'SOUL' study database) for 31 elderly schizophrenia patients. RESULTS: In both
      the fab and the MMSE tests the scores for the patients with FTD were
      significantly lower than the scores for the patients with schizophrenia.
      CONCLUSION: Our study suggests that, despite the clinical similarities, there are
      differences between patients with FTD and elderly patients with schizophrenia
      with regard to executive and general cognitive functioning. Further studies are
      needed in order to differentiate between the two illnesses.

PMID- 22588956
TI  - [The God image in relation to autistic traits and religious denomination].
AB  - BACKGROUND: Estimates of the prevalence of autism spectrum disorders (ASD) range
      from 0.6 to 1.0 per cent of the general population. Among the characteristic
      traits of ASD are qualitative impairments in social reciprocity and in abstract
      imagination. Not surprisingly, these traits can affect the personal religion of
      ASD patients, in the same manner as religious background does. AIM: To determine
      to what extent the religiousness of religious patients is associated with
      autistic traits and religious background. METHOD: Dutch adults attending a
      Protestant mental healthcare institution as outpatients were asked to complete
      the 'Questionnaire God Image' (QGI) and the 'Autism Quotient' (AQNL). In this
      cross-sectional study various aspects of the God image were related to autistic
      traits and religious background. RESULTS: The more that respondents reported
      autistic traits, the greater was their fear of God and the less positive were
      their feelings. Respondents who were strict Calvinists experienced greater fear
      of God than did other respondents. CONCLUSION: Treatment of religious patients
      with asd needs to take into account these patients' greater fear of God and their
      less positive feelings. Those patients who had had a strict Calvinist upbringing
      had a more pronounced fear of God.

PMID- 22588957
TI  - [Can the clinical items of the risk assessment instrument HKT-30 predict to what
      extent forensic patients will break agreements during the resocialisation phase
      of treatment?].
AB  - BACKGROUND: Up till now, little research has been done into the factors that
      psychologists use during a patient's Involuntary Commitment process in order to
      decide whether the patient should be transferred from the transitional phase of
      treatment to the pre-release resocialisation phase. In forensic treatment a
      premature decision can result in a problematical resocialisation phase and
      prolong the period of treatment. AIM: To find out whether the K-items of the HKT
      30, measured in the 12 months prior to the decision-making moment, can predict
      whether a patient, upon transfer to the resocialisation phase, will likely break
      agreements made in the transitional phase. METHOD: With logistic regression and
      roc-analyses, the K-items of the HKT-30 for 94 patients, measured between 2003
      and 2009, were used to predict the course and length of these patients' treatment
      in the resocialisation phase. RESULTS: Some clinical items of the HKT-30 appear
      to provide a predictive value for the course of the pre-release resocialisation
      phase. Impulsiveness is one of the risk factors affecting the resocialisation
      phase. CONCLUSION: Some K-items of the HKT-30 do appear to support the decisions
      to allow patients receiving forensic inpatient treatment to be transferred to the
      resocialisation phase.

PMID- 22588958
TI  - [Obsessive-compulsive disorder from a family perspective; implications for
      treatment and research].
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) is a chronic, psychiatric disease
      which can be highly resistant to treatment. Several studies have suggested that
      family factors may play a role in the etiology and course of OCD. AIM: To provide
      an overview of current knowledge about the complex interaction between OCD and
      family factors. METHOD: We performed a systematic search of the literature, using
      PubMed and Psychinfo. RESULTS: OCD places a heavy burden on partners and family
      members, and their responses to symptoms influence the course of the disease,
      particularly the effect of cognitive behavioural therapy (CBT). Interventions
      aimed at improving communicative skills and creating a more balanced family
      response can have a positive influence on the course of OCD. CONCLUSION: It is
      advisable to integrate family factors into the treatment of OCD. Further research
      on this topic is needed.

PMID- 22588959
TI  - [Psychotherapy and neurobiology in obsessive-compulsive disorders].

PMID- 22588960
TI  - [Is there a causal link between idiopathic intracranial hypertension and the use
      of lithium? A case-study and a review of the literature].
AB  - BACKGROUND: The first case-study of idiopathic intracranial hypertension (IIH)
      linked to the use of lithium appeared in 1978. Since then several new case
      studies have been published sporadically. A recurrent problem for therapists
      seems to be whether to continue or discontinue treatment with lithium. AIM: To
      review the literature on the alleged link between IIH and the use of lithium.
      METHOD: We performed a systematic review of published papers relating to the use
      of lithium in the treatment of IIH. RESULTS: We found 16 cases. The typical
      clinical picture of IIH was present in most of the cases. There was a large
      variation in the course of the illness. In many cases the nature of the link
      (coincidental or causal) remained unclear. Strong arguments in favour of a causal
      link were found in only two cases. CONCLUSIONS: IIH linked to the use of lithium
      is a very rare condition. In most cases it is not clear whether the link is
      coincidental or causal. If a patient being treated with lithium is definitely
      diagnosed with IIH and no other more plausible cause is found, then it is
      advisable to discontinue treatment with lithium. However, the therapist should
      feel free to re-start treatment with lithium in certain circumstances, for
      instance if patients have clearly benefited from lithium in previous maintenance
      treatment, if there is an unclear association between lithium and the onset and
      course of pseudotumour cerebri (PTC), or if the patient's condition has clearly
      deteriorated after lithium treatment has been discontinued.

PMID- 22588961
TI  - [Symptoms of anxiety in adolescents. Findings from the TRAILS-study].
AB  - BACKGROUND: The Dutch TRAILS-study focuses on development from early adolescence
      into adulthood. An important aspect of this development is the development of
      anxiety. Hitherto little has been known about typical development of symptoms of
      anxiety during adolescence. AIM: To describe both the normative development of
      anxiety during adolescence, and the risk indicators for high levels of anxiety in
      adolescents. METHOD: Studies were embedded in trails, a large cohort study that
      followed children from the age of 10 to adulthood. RESULTS: Our results showed
      that, on average, levels of anxiety decrease in early adolescence and
      subsequently increase in middle or late adolescence, depending on the subtype of
      anxiety involved. Child-, parent- and peer-factors at age 10-12 years were
      related to higher subsequent anxiety levels. Some factors, such as the style of
      upbringing, were related to higher anxiety levels solely in early adolescence,
      whereas other factors such as being bullied by peers were related to continuing
      higher anxiety levels throughout adolescence, irrespective of later
      victimisation. CONCLUSION: Our study should, we hope, lead to a better
      understanding of the normative development of anxiety in the general adolescent
      population.

PMID- 22588962
TI  - [Patients with an increased risk of developing a first psychotic episode: two
      cases].
AB  - Patients with an 'at risk mental state' (ARMS) run an increased risk of
      developing a psychosis within the near future. Patients with an arms can be
      divided into three groups: those with genetic predisposition to schizophrenia and
      displaying decreased social functioning, those with attenuated psychotic symptoms
      and those with brief limited and intermittent psychotic symptoms (BLIPS).
      Patients with an arms are often suffering from comorbid anxiety and depressive
      symptoms. Our study focuses on two patients with an ARMS.

PMID- 22588963
TI  - [Anti-NMDA-receptor encephalitis: a new axis-III disorder in the differential
      diagnosis of childhood disintegrative disorder, early onset schizophrenia and
      late onset autism].
AB  - Childhood disintegrative disorder (CDD), early onset schizophrenia (EOS), and
      late onset autism (LOA) often follow a similar course: initially, development is
      normal, then there is a sudden neuropsychiatric deterioration of social
      interaction and communication skills, which is combined with a decline in
      intelligence and reduction in daily activities. A 9-year-old boy was admitted to
      the paediatric ward with acute onset of secondary epileptic seizures. It was not
      long until the boy's symptoms resembled that of patients with cdd, eos and loa.
      Intensive tests led to the diagnosis of anti-NMDA-receptor encephalitis. Anti
      NMDA-receptor encephalitis should be regarded as a possible organic cause
      underlying the syndromal presentation of CDD, EOS and LOA.

PMID- 22588964
TI  - Soil contamination and persistence of pollutants following organophosphate sprays
      and explosions to control red-billed quelea (Quelea quelea).
AB  - BACKGROUND: Red-billed quelea (Quelea quelea) are controlled at breeding colonies
      and roosts by organophosphate sprays or explosions. Contamination with
      organophosphates after sprays and with petroleum products and phthalates after
      explosions was assessed. RESULTS: Concentrations in soil of the organophosphate
      fenthion the day after sprays were uneven (0-29.5 ug g(-1)), which was
      attributable to excess depositions at vehicle turning points, incorrect
      positioning of nozzles and poor equipment maintenance. A laboratory study using
      field-collected samples provided an estimate of 47 days for the half-life of
      fenthion. After sprays, fenthion persisted in soil for up to 188 days. High
      concentrations were detected 5 months after negative results at the same sites,
      providing indirect evidence of leaching. Concentrations of total petroleum
      hydrocarbons (TPHs) and phthalates ranged from 0.05 to 130.81 (mean 18.69) ug g(
      1) and from 0 to 1.62 (mean 0.55) ug g(-1) respectively in the craters formed by
      the explosions, but declined to means of 0.753 and 0.027 ug g(-1) at 10 m away.
      One year after an explosion, mean TPHs of 0.865 and mean phthalates of 0.609 were
      detected. CONCLUSION: Localisation of high concentrations of fenthion likely to
      have effects on soil biota could be mitigated by improved spray management. Given
      a half-life in the soil of 47 days for fenthion and the possibility of its
      leaching months after applications raises concerns about its acceptability. The
      pollutants left behind after explosions have been quantified for the first time,
      and, given their long-term persistence, their continued use poses a threat to
      environmental health.

PMID- 22588965
TI  - Chronic methylphenidate administration in mice produces depressive-like behaviors
      and altered responses to fluoxetine.
AB  - Methylphenidate (MPH) is a psychostimulant used in the treatment of attention
      deficit/hyperactivity disorder in children and adults. Increasing abuse rates of
      this drug have raised questions regarding the effects of chronic, high-dose MPH
      administration. Although the effects of chronic MPH exposure have been well
      documented in regard to reward-related behaviors in adolescent and adult animals,
      there are few studies of the effects of MPH on depressive-like behaviors and
      antidepressant responses, particularly in adult models. We examined the effects
      of chronic (14 days) high-dose (20 mg/kg i.p.) MPH exposure on locomotor activity
      and forced swim test behavior in C57Bl/6J mice. We show that MPH treatment
      ameliorates the locomotor suppression seen in response to fluoxetine. In
      addition, chronic MPH treatment produces depressive-like effects in the forced
      swim test, with decreased latency to first immobility and a trend toward
      increased immobility. These effects are reversed with acute fluoxetine
      administration, in contrast to saline-treated animals, which show no response to
      fluoxetine. The induction of depressive-like behaviors after chronic MPH
      treatment in adult mice is in agreement with previous studies in adolescent rats,
      and the marked alterations in fluoxetine responses implicate alterations in the
      serotonin system and possibly the dopamine system produced by MPH.

PMID- 22588967
TI  - Electromagnetic inductance plethysmography to measure tidal breathing in preterm
      and term infants.
AB  - Tidal breathing measurements which provide a non-invasive measure of lung
      function in preterm and term infants are particularly useful to guide respiratory
      support. We used a new technique of electromagnetic inductance plethysmography
      (EIP) to measure tidal breathing in infants between 32 and 42 weeks
      postconceptional age (PCA). Tidal breathing was measured in 49 healthy
      spontaneously breathing infants between 32 and 42 weeks PCA. The weight-corrected
      tidal volume (V(T) ) and minute volume (MV) decreased with advancing PCA (V(T)
      6.5 +/- 1.5 ml/kg and MV 0.44 +/- 0.04 L/kg/min at 32-33 weeks, respectively; 6.3
      +/- 0.9 ml/kg and 0.38 +/- 0.02 L/kg/min at 34-36 weeks; and 5.1 +/- 1.1 ml/kg
      and 0.28 +/- 0.02 L/kg/min at term, V(T) P < 0.001 and MV P < 0.01 for 32-33
      weeks PCA vs. term; V(T) P = 0.016 and MV P = 0.015 for 34-36 weeks PCA vs.
      term). Respiratory frequency and the phase angle decreased significantly with
      advancing PCA but the flow parameter t(PTEF) /t(E) did not change significantly.
      Using a new technique to measure tidal breathing parameters in newborn infants,
      our data confirms its usability in clinical practice and establishes normative
      data which can guide future respiratory management of newborn infants.

PMID- 22588968
TI  - Detection of exercise-induced pulmonary arterial hypertension by cardiopulmonary
      exercise testing.
AB  - BACKGROUND: The pulmonary arterial pressure (PAP) response to exercise may
      provide a tool for the early detection of pulmonary arterial hypertension (PAH).
      Therefore, an accurate noninvasive method for evaluating exercise-induced PAH
      (EIPAH) is desirable. HYPOTHESIS: We sought to examine if cardiopulmonary
      exercise testing (CPET) is able to indicate EIPAH. METHODS: Fifty-three patients
      aged 67.1 +/- 1.7 years (37 female, 16 male) with borderline PAH (resting mean
      PAP 21-24 mm Hg) performed CPET and right heart catheterization at rest and
      during handgrip testing. RESULTS: When comparing patients with an exercise
      induced mean PAP >= mm Hg (group A, n = 24) and subjects with an exercise-induced
      mean PAP <35 mm Hg (group B, n = 29), group A had a significantly lower mean
      aerobic capacity (15.2 +/- 1.2 vs 19.7 +/- 1.2 mL/min/kg; P = 0.02), higher
      ventilatory equivalents for oxygen at the anaerobic threshold (34.3 +/- 1.5 vs
      29.9 +/- 1.1; P = 0.02), a widening of the mean alveolar-arterial oxygen
      difference (37.8 +/- 3.0 vs 26.8 +/- 2.4 mm Hg; P = 0.007), an elevated mean
      functional dead space ventilation (29.5 +/- 2.7 vs 21.2 +/- 1.7%; P = 0.008), and
      a higher mean arterial to end-tidal carbon dioxide gradient at peak exercise (3.7
      +/- 0.9 vs 0.4 +/- 0.8 mm Hg; P = 0.007). CONCLUSIONS: EIPAH is characterized by
      a decreased ventilatory efficiency due to ventilation to perfusion inequalities.
      CPET may be useful for the identification of EIPAH and serve to diagnose PAH at
      an early stage.

PMID- 22588969
TI  - Simple analogues of qinghaosu (artemisinin).
AB  - A series of 1,2,4-trioxanes were synthesized in which the key peroxy bonds were
      installed through a molybdenum-catalyzed perhydrolysis of the epoxy rings. A core
      structure was identified that may serve as a promising lead structure for further
      investigations because of its high antimalarial activity (comparable to that of
      artesunate and chloroquine), apparent potential for scale-up and derivatization,
      and facile monitoring/tracing by using UV light.

PMID- 22588970
TI  - The subtle art of bimetallic activation: juggling carbenes, hydrocarbons, and
      hydride ligands between metals.

PMID- 22588972
TI  - The anatomy of transcription: Oscar Lee Miller (April 12, 1925-January 28, 2012).

PMID- 22588974
TI  - The comprehension of sentences involving quantity information affects responses
      on the up-down axis.
AB  - We investigated the use of space in the comprehension of the concept of quantity
      in text. Previous work has suggested that the right-left axis is useful in
      spatial representations of number and quantity, while linguistic evidence points
      toward use of the up-down axis. In Experiment 1, participants read sentences
      containing quantity information and pressed buttons in either (1) an up and a
      down position or (2) a left and a right position. In Experiment 2, the
      participants pressed buttons in either (1) up and down positions or (2) left and
      right positions, but heard the sentences rather than reading them. We found
      spatial compatibility effects for the up-down axis, but not for the right-left
      axis. Additionally, the spatial compatibility effect was observed whether or not
      the participants moved to make their responses. We discussed the results in the
      context of embodied approaches to the comprehension of quantity information.

PMID- 22588975
TI  - Resonance assignments of diastereotopic CH(2)  protons in the anomeric side chain
      of selenoglycosides by means of (2) J(Se,H) spin-spin coupling constants.
AB  - Unambiguous resonance assignments of diastereotopic CH(2) protons in the anomeric
      side chain of nine alkyl- and aralkylselenoglycosides have been carried out on
      the basis of experimental CPMG-HSQMBC measurements and theoretical second order
      polarization propagator approach (SOPPA) calculations of geminal (77) Se-(1) H
      spin-spin coupling constants involving diastereotopic pro-R and pro-S protons.
      Theoretical conformational analyses have been performed at the MP2/6-311G**
      level. The conformational space of each of the selenoglycosides under study could
      be adequately described as a mixture of six interconverting conformers with the
      molar fractions depending on the nature of the side chain substituent at the
      selenium atom. The good agreement observed between measured and the weighted
      conformational averaged values of the calculated coupling constants provides a
      basis for reliable diastereotopic assignments in this type of carbohydrate
      structures.

PMID- 22588977
TI  - Commentary: ion channels, fusion pores and exocytosis.

PMID- 22588976
TI  - Electromagnetic field stimulation potentiates endogenous myelin repair by
      recruiting subventricular neural stem cells in an experimental model of white
      matter demyelination.
AB  - Electromagnetic fields (EMFs) may affect the endogenous neural stem cells within
      the brain. The aim of this study was to assess the effects of EMFs on the process
      of toxin-induced demyelination and subsequent remyelination. Demyelination was
      induced using local injection of lysophosphatidylcholine within the corpus
      callosum of adult female Sprague-Dawley rats. EMFs (60 Hz; 0.7 mT) were applied
      for 2 h twice a day for 7, 14, or 28 days postlesion. BrdU labeling and
      immunostaining against nestin, myelin basic protein (MBP), and BrdU were used for
      assessing the amount of neural stem cells within the tissue, remyelination
      patterns, and tracing of proliferating cells, respectively. EMFs significantly
      reduced the extent of demyelinated area and increased the level of MBP staining
      within the lesion area on days 14 and 28 postlesion. EMFs also increased the
      number of BrdU- and nestin-positive cells within the area between SVZ and lesion
      as observed on days 7 and 14 postlesion. It seems that EMF potentiates
      proliferation and migration of neural stem cells and enhances the repair of
      myelin in the context of demyelinating conditions.

PMID- 22588978
TI  - Commentary: neurotransmitter secretion and cell signaling.

PMID- 22588979
TI  - Proceedings of the 16th International Symposium on Chromaffin Cell Biology.

PMID- 22588980
TI  - Orexin A suppresses the growth of rat C6 glioma cells via a caspase-dependent
      mechanism.
AB  - Orexin A and orexin B (also known as hypocretins) are closely related peptides
      synthesized by hypothalamic neurons. They orchestrate diverse central and
      peripheral processes by stimulation of two G-protein coupled receptors, OX(1)R
      and OX(2)R. Recent studies have demonstrated the ability of orexins to promote a
      robust apoptosis in different cancer cells in culture and a potent growth
      reduction of human colon tumors in mice xenografts. Here we report effects of
      orexins on survival of rat C6 glioma cells, an experimental model for studies on
      glioblastoma multiforme (GBM). Quantitative real-time PCR demonstrated the
      expression of both types of orexin receptors in C6 cells. Orexin A and orexin B
      did not affect rat C6 glioma cell proliferation as assessed by [(3)H]thymidine
      incorporation assay. Incubation of the cells with orexin A (0.001-1 MUM) resulted
      in a marked decrease of cell viability. The observed effect was caspase
      dependent, as it was blocked by Z-VAD-fmk, a pan caspase inhibitor. In addition
      to that, a parallel increase in caspase-3 activity was observed. It is suggested
      that stimulation of orexin receptors induces death of rat C6 glioma cells through
      activation of caspase pathway.

PMID- 22588982
TI  - Choice with delayed or uncertain reinforcers in rats: influence of timeout
      duration and session length.
AB  - Interest is rising for animal modeling of impaired behavioral inhibition.
      Impulsivity and risk proneness, key symptoms of impulse-control disorders, are
      classically measured by Intolerance to Delay (ID) and Probabilistic Delivery (PD)
      tasks, requiring choice between a "Small & Soon" or "Sure" (SS) versus a "Large &
      Late" or "Luck-Linked" (LL or LLL, respectively) reinforcer. Several temporal
      parameters shall be set, which are not always explicit. Here, we focused on
      duration of timeout (TO; three groups: 15, 30, or 45 s; Exp. 1) and on session
      length (SL; three groups: 60, 90, or 120 min; Exp. 2) to determine whether these
      parameters may affect rats' performance in ID and PD tasks, respectively. In Exp.
      1, rats' reaction to increasing experimental delays (absolute values 0-90 s,
      delay-equivalent odds 0 to 1.94 +/- 0.11) was critically affected by TO duration:
      a steeper impulsivity curve was found in subjects tested with the longest TO,
      while random performance was elicited with too short TO. In Exp. 2, a specific
      "gambling" part was presented (LLL probability lower than 20%). Subjects tested
      with the shortest session length (60 min), who had a low number of gambling
      opportunities (performed trials = 84.33 +/- 1.91), exhibited a profile of risk
      proneness, with sustained LLL preference despite high uncertainty and low payoff.
      Present data demonstrate that TO and SL crucially influence rats' performance in
      these operant tasks. Their methodological refinement is highly relevant to
      validate preclinical models for inhibitory-control impairments.

PMID- 22588981
TI  - F-actin-myosin II inhibitors affect chromaffin granule plasma membrane distance
      and fusion kinetics by retraction of the cytoskeletal cortex.
AB  - Chromaffin cell catecholamines are released when specialized secretory vesicles
      undergo exocytotic membrane fusion. Evidence indicates that vesicle supply and
      fusion are controlled by the activity of the cortical F-actin-myosin II network.
      To study in detail cell cortex and vesicle interactions, we use fluorescent
      labeling with GFP-lifeact and acidotropic dyes in confocal and evanescent wave
      microscopy. These techniques provide structural details and dynamic images of
      chromaffin granules caged in a complex cortical structure. Both the movement of
      cortical structures and granule motion appear to be linked, and this motion can
      be restricted by the myosin II-specific inhibitor, blebbistatin, and the F-actin
      stabilizer, jasplakinolide. These treatments also affect the position of the
      vesicles in relation to the plasma membrane, increasing the distance between them
      and the fusion sites. Consequently, we observed slower single vesicle fusion
      kinetics in treated cells after neutralization of acridine orange-loaded granules
      during exocytosis. Increasing the distance between the granules and the fusion
      sites appears to be linked to the retraction of the F-actin cytoskeleton when
      treated with jasplakinolide. Thus, F-actin-myosin II inhibitors appear to slow
      granule fusion kinetics by altering the position of vesicles after relaxation of
      the cortical network.

PMID- 22588983
TI  - Bonferroni-based correction factor for multiple, correlated endpoints.
AB  - Multiple testing and its impact on the type I and type II error rates are
      frequently discussed in the statistical and biomedical literature. The Bonferroni
      adjustment is one of the most widely used approaches, yet it suffers from poor
      statistical performance when there are correlated test statistics. For example,
      it is criticized to be too conservative. Nonetheless, part of the strong appeal
      of the Bonferroni approach is the straightforward implementation and relatively
      intuitive explanation. In this manuscript, a novel adaptation to the traditional
      Bonferroni approach that accounts for correlated data is proposed. A simple
      correction factor based on intraclass correlation is applied to the standard
      Bonferroni method to overcome the shortcomings of the standard Bonferroni
      adjustment yet maintains its advantages. The method is motivated by an early
      phase clinical trial examining the effect of a study medication on marijuana
      craving, which is commonly quantified into four correlated constructs. A detailed
      simulation study demonstrated that the proposed approach is statistically sound
      and appropriate for a wide range of common settings.

PMID- 22588984
TI  - Assembly of single-stranded DNA onto HOPG surface at different temperature:
      atomic force microscopy study.
AB  - Assembly of long single-stranded DNA (ssDNA) and short oligodeoxynucleotides onto
      bare highly oriented pyrolytic graphite (HOPG) at different temperature has been
      studied. It was indicated that both long ssDNA and oligodeoxynucleotides can
      sequentially form network, straight chains, and layer structures when the
      adsorption temperature was changed from room temperature, 37-55 degrees C. High
      resolution atomic force microscopy (AFM) imaging of the layer structures revealed
      that they are composed of parallel ssDNA chains with relatively higher height and
      tend to form patterns with three-fold symmetry. These new findings are
      significantly important for understanding assembly characterization of ssDNA. In
      addition, this assembly method for ssDNA is expected to be used for preparation
      of DNA structures in biosensing and DNA-based nanodevices.

PMID- 22588985
TI  - Magnetic nanoparticles entrapped in siliceous mesocellular foam: a new catalyst
      support.
AB  - gamma-Fe(2)O(3) nanoparticles were formed inside the cage-like pores of
      mesocellular foam (MCF). These magnetic nanoparticles showed a uniform size
      distribution that could be easily controlled by the MCF pore size, as well as by
      the hydrocarbon chain length used for MCF surface modification. Throughout the
      entrapment process, the pore structure and surface area of the MCF remained
      intact. The resulting magnetic MCF facilitated the immobilization of
      biocatalysts, homogeneous catalysts, and nanoclusters. Moreover, the MCF allowed
      for facile catalyst recovery by using a simple magnet. The supported catalysts
      exhibited excellent catalytic efficiencies that were comparable to their
      homogeneous counterparts.

PMID- 22588986
TI  - Pediatric fiberoptic bronchoscopy as adjunctive therapy in acute asthma with
      respiratory failure.
AB  - BACKGROUND: Status asthmaticus respiratory failure is associated with thickened
      mucus secretions necessitating aggressive pulmonary clearance. The role of
      bronchoscopy in pediatric mechanically ventilated asthmatic patients has not been
      published. METHODS: A chart review was performed on all pediatric intensive care
      unit (PICU) asthmatics with respiratory failure over 13 years. Forty-four
      patients were identified. Patients were managed per standardized guidelines for
      status asthmaticus with mechanical ventilation. Ventilator management prioritized
      spontaneous breathing with pressure support. Extubation criteria included
      spontaneous tidal volumes of 5-7 cm(3) /kg on low-pressure support. Standard
      endotracheal tube pulmonary toilet were implemented. Twenty-nine patients
      underwent bronchoscopy as an adjunctive therapy. Indications for bronchoscopy
      included: Pathogen identification via bronchoalveolar ravage, atelectasis, mucus
      obstruction resulting in severe air trapping, suspected aspiration, and poor
      response to standard therapy. Clinical outcomes of this intervention were
      compared to the fifteen patient cohort who did not undergo bronchoscopy. RESULTS:
      Bronchoscopies revealed thick mucus plugs, secretions, and bronchial casts. The
      large airways were lavaged for clearance of obstructive secretions with normal
      saline. All patients tolerated the procedure without any complications.
      Demonstrable improvement in pulmonary compliance was noted. The median time of
      intubation for the bronchoscopy group was 10 hr compared to 20.5 hr for the
      control group (P < 0.0005). The mean intensive care unit length of stay was 3.06
      days for the bronchoscopy group versus 3.4 days for the non-bronchoscopy group (P
      < 0.05). CONCLUSION: Flexible bronchoscopy with bronchial lavage is a safe
      adjunctive therapy in pediatric asthmatics with respiratory failure resulting in
      reduced mechanical ventilation and intensive care length of stay. Restoring lung
      volume in certain asthmatics during respiratory failure may be deemed beneficial.
      Further validated studies are necessary to recommend bronchoscopy to the present,
      accepted treatment regimen in pediatric asthmatic respiratory failure.

PMID- 22588987
TI  - Correlates of motivation to change in pathological gamblers completing cognitive
      behavioral group therapy.
AB  - OBJECTIVES: The present study analyzes the association between the motivation to
      change and the cognitive-behavioral group intervention, in terms of dropouts and
      relapses, in a sample of male pathological gamblers. The specific objectives were
      as follows: (a) to estimate the predictive value of baseline University of Rhode
      Island Change Assessment scale (URICA) scores (i.e., at the start of the study)
      as regards the risk of relapse and dropout during treatment and (b) to assess the
      incremental predictive ability of URICA scores, as regards the mean change
      produced in the clinical status of patients between the start and finish of
      treatment. METHOD: The relationship between the URICA and the response to
      treatment was analyzed by means of a pre-post design applied to a sample of 191
      patients who were consecutively receiving cognitive-behavioral group therapy. The
      statistical analysis included logistic regression models and hierarchical
      multiple linear regression models. RESULTS: The discriminative ability of the
      models including the four URICA scores regarding the likelihood of relapse and
      dropout was acceptable (area under the receiver operating haracteristic curve:
      .73 and .71, respectively). No significant predictive ability was found as
      regards the differences between baseline and posttreatment scores (changes in
      R(2) below 5% in the multiple regression models). CONCLUSIONS: The availability
      of useful measures of motivation to change would enable treatment outcomes to be
      optimized through the application of specific therapeutic interventions.

PMID- 22588988
TI  - Assessing the local identifiability of probabilistic knowledge structures.
AB  - Given a collection Q of problems, in knowledge space theory Doignon & Falmagne,
      (International Journal of Man-Machine Studies 23:175-196, 1985) the knowledge
      state of a student is the collection K ? Q of all problems that this student is
      capable of solving. A knowledge structure is a pair (Q, ), where is a collection
      of knowledge states that contains at least the empty set and Q. A probabilistic
      knowledge structure (PKS) is a knowledge structure (Q, , pi), where pi is a
      probability distribution on the knowledge states. The PKS that has received the
      most attention is the basic local independence model BLIM; Falmagne & Doignon,
      (British Journal of Mathematical and Statistical Psychology 41:1-23, 1988a,
      Journal of Mathematical Psychology 32:232-258, 1988b). To the best of our
      knowledge, systematic investigations in the literature concerning the
      identifiability of the BLIM are totally missing. Based on the theoretical work of
      Bamber and van Santen (Journal of Mathematical Psychology 29:443-473, 1985), the
      present article is aimed to present a method and a corresponding computerized
      procedure for assessing the local identifiability of the BLIM, which is
      applicable to any finite knowledge structure of moderate size.

PMID- 22588989
TI  - Effect of calcination temperature and pretreatment with reaction gas on
      properties of Co/gamma-Al2O3 catalysts for partial oxidation of methane.
AB  - The effects of calcination temperature and feedstock pretreatment on the
      catalytic performance of Co/gamma-Al(2)O(3) catalysts were studied for partial
      oxidation of methane (POM) to synthesis gas, with emphasis on the role of
      feedstock pretreatment. The physicochemical properties of the catalysts were
      characterized by N(2) adsorption, X-ray diffraction (XRD), transmission electron
      microscopy (TEM), H(2) temperature-programmed reduction (H(2) -TPR), and Raman
      spectroscopy. The results showed that the pretreatment of the catalyst by
      reaction gas significantly improved the catalytic activity and stability for the
      POM reaction. On the other hand, the effect of calcination temperature was less
      significant. Although the initial activity was increased by an increased
      calcination temperature, the catalyst without the feedstock pretreatment suffered
      a rapid deactivation. The reaction-atmosphere pretreatment was revealed as a
      process that mainly modified the surface structure of the catalyst. In that
      process, the formation of a CoAl(2)O(4) -like compound led to high Co metal
      dispersion after reduction, and the transformation of the carrier into alpha
      Al(2)O(3) occurred over the catalyst surface. Both the high dispersion of cobalt
      and the presence of alpha-Al(2)O(3) surface phase were assumed as the important
      factors resulting in an excellent catalytic performance in terms of high activity
      and high stability.

PMID- 22588991
TI  - Magnetic resonance imaging in valvular heart disease: clinical application and
      current role for patient management.
AB  - Noninvasive imaging provides important information on cardiac anatomy and
      function and is a key element in clinical management of valvular heart disease
      (VHD). Beside echocardiography, which is still considered the first-line modality
      for assessment of valvular anatomy and longitudinal evaluation of VHD,
      cardiovascular magnetic resonance (CMR) has evolved during the last two decades
      as an essential tool for evaluation of cardiac diseases. Today, CMR not only
      represents the reference standard for measuring cardiac volumes, function, and
      mass, but also enables accurate assessment of morphology and function of cardiac
      valves. It can play an important role in clinical decision-making for patients
      with VHD. This review addresses current applications and limitations of CMR
      imaging techniques that are used in VHD including cine-balanced steady-state free
      precession (b-SSFP), phase contrast MR (pcMR), gradient-recalled echo (GRE), and
      turbo-spin echo (TSE) sequences. Moreover, it describes their application for
      evaluation of valvular pathologies and gives an overview on the current role of
      valvular CMR in patient management.

PMID- 22588992
TI  - Skeletal muscle BOLD MRI: from underlying physiological concepts to its
      usefulness in clinical conditions.
AB  - Blood oxygenation-level dependent (BOLD) MRI has gained particular attention in
      functional brain imaging studies, where it can be used to localize areas of brain
      activation with high temporal resolution. To a higher degree than in the brain,
      skeletal muscles show extensive but transient alterations of blood flow between
      resting and activation state. Thus, there has been interest in the application of
      the BOLD effect in studying the physiology of skeletal muscles (healthy and
      diseased) and its possible application to clinical practice. This review outlines
      the potential of skeletal muscle BOLD MRI as a diagnostic tool for the evaluation
      of physiological and pathological alterations in the peripheral limb perfusion,
      such as in peripheral arterial occlusive disease. Moreover, current knowledge is
      summarized regarding the complex mechanisms eliciting BOLD effect in skeletal
      muscle. We describe technical fundaments of the procedure that should be taken
      into account when performing skeletal muscle BOLD MRI, including the most often
      applied paradigms to provoke BOLD signal changes and key parameters of the
      resulting time courses. Possible confounding effects in muscle BOLD imaging
      studies, like age, muscle fiber type, training state, and drug effects are also
      reviewed in detail.

PMID- 22588993
TI  - Gradient echo imaging.
AB  - Magnetic resonance imaging (MRI) based on gradient echoes is used in a wide
      variety of imaging techniques and clinical applications. Gradient echo sequences
      form the basis for an essential group of imaging methods that find widespread use
      in clinical practice, particularly when fast imaging is important, as for example
      in cardiac MRI or contrast-enhanced MR angiography. However, the term "gradient
      echo sequence" is somewhat unspecific, as even images acquired with the most
      common sequences employing the gradient echo for data acquisition can
      significantly differ in signal, contrast, artifact behavior, and sensitivity to,
      eg, flow. This is due to the different use of sequence timing and basic sequence
      building blocks such as spoiler gradients or specific radiofrequency (RF) pulse
      phase patterns. In this article the basic principles of gradient echo formation
      compared to spin echo imaging are reviewed and the properties of gradient echo
      imaging in its simplest form (TR ? T(2)) are described. Further, the most common
      three variants of fast gradient echo sequences (TR < T(2)), namely, unbalanced
      gradient echo, RF spoiled gradient echo, and balanced steady state free
      precession; are discussed. For each gradient echo sequence type, examples of
      applications exploiting the specific properties of the individual technique are
      presented.

PMID- 22588995
TI  - Participation in voluntary organizations and volunteer work as a compensation for
      the absence of work or partnership? Evidence from two German samples of younger
      and older adults.
AB  - OBJECTIVES: We tested whether formal volunteering, in terms of its associations
      with mental health, compensates for the absence of major work and family roles
      among older adults or rather complements such roles among both younger and older
      adults. METHOD: Two cross-sectional samples of younger (aged 18-42 years, N =
      2,346) and older (aged 56-75 years, N = 1,422) German adults were used. We
      regressed mental health indicators on control variables, 2 indicators of formal
      volunteering (participation in voluntary organizations and volunteer work), and
      their interactions with employment/partnership status. RESULTS: Participation in
      voluntary organizations was associated with higher positive affect, higher life
      satisfaction, and fewer depressive symptoms in younger adults. In older adults,
      it was related to higher life satisfaction only among working individuals,
      although the difference from nonworking individuals was not significant.
      Volunteer work was associated with higher positive affect in both age groups. In
      younger adults, it had no relation to life satisfaction and depressive symptoms.
      In older adults, it was related to higher life satisfaction among nonworking
      individuals and to fewer depressive symptoms among those without a steady
      partner. DISCUSSION: Volunteer work but not participation in voluntary
      organizations yielded compensatory effects on mental health among older adults.

PMID- 22588997
TI  - Genetic interactions of yeast NEP1 (EMG1), encoding an essential factor in
      ribosome biogenesis.
AB  - Nep1 methylates the hypermodified psi1191 base of 18S rRNA and has an additional
      essential function during ribosome biogenesis. It is strongly conserved in
      eukaryotes and a point mutation causes the human Bowen-Conradi syndrome. To
      identify Deltanep1-specific genetic interactions, viable deletions were screened
      genome-wide (SGA). Due to its essential function, we used, for the first time,
      query strain (Deltanep1) with two additive suppressor conditions (mcRPS19B, nop6
      1). Nep1 interacting genes correspond to ribosome biogenesis (RPS18A, RPS18B,
      RRP8, EFG1, UTP30), to ribosome quality control (UBP3, BRE5, UBP6) and to
      ribosome functional control (DOM34, no-go decay). Deletions in ribosome quality
      and functional control genes were synthetically sick with Deltanep1. They cope
      with malfunctions and the respective deletions strengthen the Deltanep1 growth
      deficiency. Except for Deltarps18b, deletions in the identified ribosome
      biogenesis genes were synthetically lethal with Deltanep1. While the synthetic
      lethalities of Deltarrp8 and Deltaefg1 may result from additive defects, the
      Deltautp30 deletion seems to be in close functional relationship. The Deltautp30
      deletion itself has no phenotype but it enforced all nep1-1(ts) mutant
      phenotypes. Furthermore, its overexpression partially restored the nep1-1(ts)
      growth deficiency. Our genetic and biochemical data suggest that Utp30 and Nep1
      act together during pre-ribosomal complex formation and, along with Rps18,
      provide the surface for the Rps19 assembly to the 90S pre-ribosome.

PMID- 22588996
TI  - The social patterns of a biological risk factor for disease: race, gender,
      socioeconomic position, and C-reactive protein.
AB  - OBJECTIVE: Understand the links between race and C-reactive protein (CRP), with
      special attention to gender differences and the role of class and behavioral risk
      factors as mediators. METHOD: This study utilizes the National Social Life,
      Health, and Aging Project data, a nationally representative study of older
      Americans aged 57-85 to explore two research questions. First, what is the
      relative strength of socioeconomic versus behavioral risk factors in explaining
      race differences in CRP levels? Second, what role does gender play in
      understanding race differences? Does the relative role of socioeconomic and
      behavioral risk factors in explaining race differences vary when examining men
      and women separately? RESULTS: When examining men and women separately,
      socioeconomic and behavioral risk factor mediators vary in their importance.
      Indeed, racial differences in CRP among men aged 57-74 are little changed after
      adjusting for both socioeconomic and behavioral risk factors with levels 35%
      higher for black men as compared to white men. For women aged 57-74, however,
      behavioral risk factors explain 30% of the relationship between race and CRP.
      DISCUSSION: The limited explanatory power of socioeconomic position and,
      particularly, behavioral risk factors, in elucidating the relationship between
      race and CRP among men, signals the need for research to examine additional
      mediators, including more direct measures of stress and discrimination.

PMID- 22588999
TI  - Miniature release events of glutamate from hippocampal neurons are influenced by
      the dystonia-associated protein torsinA.
AB  - TorsinA is an evolutionarily conserved AAA+ ATPase, and human patients with an in
      frame deletion of a single glutamate (DeltaE) codon from the encoding gene suffer
      from autosomal-dominant, early-onset generalized DYT1 dystonia. Although only 30
      40% of carriers of the mutation show overt motor symptoms, most experience
      enhanced excitability of the central nervous system. The cellular mechanism
      responsible for this change in excitability is not well understood. Here we show
      the effects of the DeltaE-torsinA mutation on miniature neurotransmitter release
      from neurons. Neurotransmitter release was characterized in cultured hippocampal
      neurons obtained from wild-type, heterozygous, and homozygous DeltaE-torsinA
      knock-in mice using two approaches. In the first approach, patch-clamp
      electrophysiology was used to record glutamate-mediated miniature excitatory
      postsynaptic currents (mEPSCs) in the presence of the Na+ channel blocker
      tetrodotoxin (TTX) and absence of GABA(A) receptor antagonists. The intervals
      between mEPSC events were significantly shorter in neurons obtained from the
      mutant mice than in those obtained from wild-type mice. In the second approach,
      the miniature exocytosis of synaptic vesicles was detected by imaging the
      unstimulated release of FM dye from the nerve terminals in the presence of TTX.
      Cumulative FM dye release was higher in neurons obtained from the mutant mice
      than in those obtained from wild-type mice. The number of glutamatergic nerve
      terminals was also assessed, and we found that this number was unchanged in
      heterozygous relative to wild-type neurons, but slightly increased in homozygous
      neurons. Notably, in both heterozygous and homozygous neurons, the unitary
      synaptic charge during each mEPSC event was unchanged. Overall, our results
      suggest more frequent miniature glutamate release in neurons with DeltaE-torsinA
      mutations. This change may be one of the underlying mechanisms by which the
      excitability of the central nervous system is enhanced in the context of DYT1
      dystonia. Moreover, qualitative differences between heterozygous and homozygous
      neurons with respect to certain synaptic properties indicate that the
      abnormalities observed in homozygotes may reflect more than a simple gene dosage
      effect.

PMID- 22588998
TI  - Reference genes for measuring mRNA expression.
AB  - The aim of this review is to find answers to some of the questions surrounding
      reference genes and their reliability for quantitative experiments. Reference
      genes are assumed to be at a constant expression level, over a range of
      conditions such as temperature. These genes, such as GADPH and beta-actin, are
      used extensively for gene expression studies using techniques like quantitative
      PCR. There have been several studies carried out on identifying reference genes.
      However, a lot of evidence indicates issues to the general suitability of these
      genes. Recent studies had shown that different factors, including the environment
      and methods, play an important role in changing the expression levels of the
      reference genes. Thus, we conclude that there is no reference gene that can
      deemed suitable for all the experimental conditions. In addition, we believe that
      every experiment will require the scientific evaluation and selection of the best
      candidate gene for use as a reference gene  to obtain reliable scientific
      results.

PMID- 22589000
TI  - Sidestream microstream end tidal carbon dioxide measurements and blood gas
      correlations in neonatal intensive care unit.
AB  - OBJECTIVE: The study was designed to assess the use of newer sidestream
      microstream end tidal carbon dioxide (ETCO(2) ) device in predicting blood carbon
      dioxide (PCO(2) ) measurements in very low birth weight (VLBW = birth weight
      <1,500 g) and non-VLBW NICU neonates. STUDY DESIGN: Sidestream microstream
      ETCO(2) detectors were allowed time to calibrate and reach steady state prior to
      blood gas measurements. Blood CO(2) (PCO(2) ) and simultaneous ETCO(2) were
      recorded. Ratio of dead space to tidal volume (VD/VT) was calculated using
      modified Bohr's equation. Correlation coefficient, estimates of difference,
      standard deviation, and 95% limits of agreement between ETCO(2) and PCO(2)
      concentrations were calculated. RESULTS: Two hundred eighty-six paired samples
      were collected from 48 ventilated NICU patients. Average PCO(2) and ETCO(2) were
      58.4 and 50.6 with a correlation of 0.76. Subgroup analysis showed a correlation
      of 0.73 in 204 paired blood from 34 VLBW infants and 0.82 in 82 paired samples
      from non-VLBW infants. Estimates of difference +/- standard deviation between
      PCO(2) and ETCO(2) concentrations in these three groups, respectively (ALL, VLBW,
      and non-VLBW) were 7.84 +/- 9.96, 8.2 +/- 10.16, and 6.95 +/- 9.45. The
      correlation coefficient significantly improved in the VLBW group to 0.86 with
      dead space to tidal volume ratio (VD/VT) <30% (0.86 vs. 0.42; P < 0.001).
      CONCLUSION: ETCO(2) measurements using sidestream microstream technology in VLBW
      demonstrated that the correlation of ETCO(2) and PCO(2) was moderate, but the
      agreement was less than adequate (bias > 5 mmHg in all groups). The results
      improved with lower VD/VT, suggesting that sidestream capnography is more
      reliable in conditions of less severe lung disease.

PMID- 22589002
TI  - Repetitive nonsuicidal self-injury as experiential avoidance among a community
      sample of adolescents.
AB  - OBJECTIVE: This study examined the relationship between experiential avoidance,
      functionally equivalent behaviors, and repetitive nonsuicidal self-injury
      (NSSI/RNSSI) among adolescents. METHOD: Self-report questionnaires from
      adolescents (N = 211) from 3 school-based samples were employed to assess three
      forms of experiential avoidance (thought suppression, alexithymia, and
      avoidance/cognitive fusion), various aspects of self-mutilating behaviors, and
      the existence of functionally equivalent behaviors (disordered eating, substance
      abuse, suicidal ideation/behaviors). RESULTS: Results indicated one third of
      participants reported a history of NSSI and 16% reported engaging in RNSSI in the
      past 6 months. Female adolescents were twice as likely as males to report a
      history of RNSSI. Unwanted inner experiences, thought suppression, and
      alexithymia differentiated adolescents with a history of NSSI from their
      counterparts. Functionally equivalent behaviors occurred more frequently among
      those with a history of NSSI and increased in severity as NSSI increased,
      particularly suicidal ideation and behaviors. However, results for patterns of
      avoidance were not as consistent for males as females, which questions the broad
      application of this model. CONCLUSIONS: NSSI continues to be surprisingly common
      among adolescents in the community. NSSI, particularly repetitive forms, appears
      to be strongly related to common forms of experiential avoidance, moreso for
      female adolescents. Results also illustrate the importance of conceptualizing and
      treating self-injury as a form of experiential avoidance.

PMID- 22589004
TI  - Boronic acid catalysis as a mild and versatile strategy for direct carbo- and
      heterocyclizations of free allylic alcohols.

PMID- 22589003
TI  - Leisure inequality in the United States: 1965-2003.
AB  - This article exploits the complex sequential structure of the diary data in the
      American Heritage Time Use Study (AHTUS) and constructs three classes of
      indicators that capture the quality of leisure (pure leisure, co-present leisure,
      and leisure fragmentation) to show that the relative growth in leisure time
      enjoyed by low-educated individuals documented in previous studies has been
      accompanied by a relative decrease in the quality of that leisure time. These
      results are not driven by any single leisure activity, such as time spent
      watching television. Our findings may offer a more comprehensive picture of
      inequality in the United States and provide a basis for weighing the relative
      decline in earnings and consumption for the less-educated against the
      simultaneous relative growth of leisure.

PMID- 22589005
TI  - Chip-scale microscopy imaging.
AB  - Chip-scale microscopy imaging platforms are pivotal for improving the efficiency
      of modern biomedical and bioscience experiments. Their integration with other lab
      on-a-chip techniques would allow rapid, reliable and high-throughput sample
      analysis for applications in diverse disciplines. In typical chip-scale
      microscopy imaging platforms, the light path can be generalized to the following
      steps: photons leave the light source, interact with the sample and finally are
      detected by the sensor. Based on the light path of these platforms, the current
      review aims to provide some insights on design strategies for chip-scale
      microscopy. Specifically, we analyze current chip-scale microscopy approaches
      from three aspects: illumination design, sample manipulation and substrate/imager
      modification. We also discuss some opportunities for future developments of chip
      scale microscopy, such as time multiplexed structured illumination and
      hydrodynamic focusing for high throughput sample manipulation.

PMID- 22589010
TI  - Fragility fractures of the pelvis.
AB  - Fragility fractures of the pelvis are common and the incidence is increasing with
      the aging population. The primary risk factor is osteoporosis. Diagnosis is
      challenging and advanced imaging with computed tomography (CT), bone
      scintigraphy, and magnetic resonance imaging (MRI) is helpful. These injuries
      result in significant morbidity, including prolonged hospitalization, immobility,
      and loss of autonomy in previously active patients. The mortality rate is high,
      similar to hip fracture patients. This problem is underappreciated and deserves
      attention. An opportunity exists to improve outcomes with medical and surgical
      management.

PMID- 22589006
TI  - The effect of thoracic kyphosis and sagittal plane alignment on vertebral
      compressive loading.
AB  - To better understand the biomechanical mechanisms underlying the association
      between hyperkyphosis of the thoracic spine and risk of vertebral fracture and
      other degenerative spinal pathology, we used a previously validated
      musculoskeletal model of the spine to determine how thoracic kyphosis angle and
      spinal posture affect vertebral compressive loading. We simulated an age-related
      increase in thoracic kyphosis (T(1) -T(12) Cobb angle 50-75 degrees) during two
      different activities (relaxed standing and standing with 5-kg weights in the
      hands) and three different posture conditions: (1) an increase in thoracic
      kyphosis with no postural adjustment (uncompensated posture); (2) an increase in
      thoracic kyphosis with a concomitant increase in pelvic tilt that maintains a
      stable center of mass and horizontal eye gaze (compensated posture); and (3) an
      increase in thoracic kyphosis with a concomitant increase in lumbar lordosis that
      also maintains a stable center of mass and horizontal eye gaze (congruent
      posture). For all posture conditions, compressive loading increased with
      increasing thoracic kyphosis, with loading increasing more in the thoracolumbar
      and lumbar regions than in the mid-thoracic region. Loading increased the most
      for the uncompensated posture, followed by the compensated posture, with the
      congruent posture almost completely mitigating any increases in loading with
      increased thoracic kyphosis. These findings indicate that both thoracic kyphosis
      and spinal posture influence vertebral loading during daily activities, implying
      that thoracic kyphosis measurements alone are not sufficient to characterize the
      impact of spinal curvature on vertebral loading.

PMID- 22589011
TI  - Is the exponent 3/2 justified in analysis of loading curve of pyramidal
      nanoindentations?
AB  - Kaupp and Naimi-Jamal (2010) claimed that the analysis of published loading
      curves reveals the exponent 3/2 to the depth for nanoindentations with sharp
      pyramidal or conical tips. To demonstrate this, they plotted the load vs. the
      penetration depth to the power 3/2. We show, through examples, the authors'
      assertion is not credible because the methodology used is misleading and it
      cannot be asserted that the exponent 3/2 has a universal validity that applies to
      all kinds of materials.

PMID- 22589013
TI  - Comment on 'Inference on treatment effects for targeted clinical trials under
      enrichment design', Jen-Pei Liu, Jr-Rung Lin, and Shein-Chung Chow;
      Pharmaceutical Statistics 2009; 8:356-370.

PMID- 22589014
TI  - Highly efficient redox isomerisation of allylic alcohols catalysed by pyrazole
      based ruthenium(IV) complexes in water: mechanisms of bifunctional catalysis in
      water.
AB  - The catalytic activity of ruthenium(IV) ([Ru(eta(3):eta(3)-C(10)H(16))Cl(2)L];
      C(10)H(16) = 2,7-dimethylocta-2,6-diene-1,8-diyl, L = pyrazole, 3-methylpyrazole,
      3,5-dimethylpyrazole, 3-methyl-5-phenylpyrazole, 2-(1H-pyrazol-3-yl)phenol or
      indazole) and ruthenium(II) complexes ([Ru(eta(6)-arene)Cl(2)(3,5
      dimethylpyrazole)]; arene = C(6)H(6), p-cymene or C(6)Me(6)) in the redox
      isomerisation of allylic alcohols into carbonyl compounds in water is reported.
      The former show much higher catalytic activity than ruthenium(II) complexes. In
      particular, a variety of allylic alcohols have been quantitatively isomerised by
      using [Ru(eta(3):eta(3)-C(10)H(16))Cl(2)(pyrazole)] as a catalyst; the reactions
      proceeded faster in water than in THF, and in the absence of base. The
      isomerisations of monosubstituted alcohols take place rapidly (10-60 min, turn
      over frequency = 750-3000 h(-1)) and, in some cases, at 35  degrees C in 60 min.
      The nature of the aqueous species formed in water by this complex has been
      analysed by ESI-MS. To analyse how an aqueous medium can influence the mechanism
      of the bifunctional catalytic process, DFT calculations (B3LYP) including one or
      two explicit water molecules and using the polarisable continuum model have been
      carried out and provide a valuable insight into the role of water on the activity
      of the bifunctional catalyst. Several mechanisms have been considered and imply
      the formation of aqua complexes and their deprotonated species generated from
      [Ru(eta(3):eta(3)-C(10)H(16))Cl(2)(pyrazole)]. Different competitive pathways
      based on outer-sphere mechanisms, which imply hydrogen-transfer processes, have
      been analysed. The overall isomerisation implies two hydrogen-transfer steps from
      the substrate to the catalyst and subsequent transfer back to the substrate. In
      addition to the conventional Noyori outer-sphere mechanism, which involves the
      pyrazolide ligand, a new mechanism with a hydroxopyrazole complex as the active
      species can be at work in water. The possibility of formation of an enol, which
      isomerises easily to the keto form in water, also contributes to the efficiency
      in water.

PMID- 22589015
TI  - Dissociative experiences as mediators between childhood trauma and auditory
      hallucinations.
AB  - The purpose of this work was to study the relationship between reported traumatic
      experiences in childhood and positive psychotic symptoms. We hypothesized that
      dissociative experiences were potential mediators between childhood trauma and
      hallucinations, but not delusions. The sample comprised 71 patients diagnosed
      with psychoses. They were assessed with the Dissociative Experiences Scale (DES
      II; Carlson & Putnam, 1993), a questionnaire on trauma (TQ; Davidson, Hughes, &
      Blazer, 1990), and the Positive and Negative Syndrome Scale (PANSS; Kay, Opler, &
      Lindenmayer, 1988) delusions and hallucinations items. The results showed that
      childhood trauma was positively associated with the dissociation scale scores (r
      = .40) and also the hallucination (r = .36) and delusions scale scores (r = .32).
      Furthermore, it was demonstrated that the dissociation variable was a potential
      mediator between childhood trauma and hallucinations, but not between childhood
      trauma and delusions. Of the 3 DES-II factors, only depersonalization showed a
      mediating relationship between childhood trauma and hallucinations. The main
      conclusion is that the impact of childhood trauma on hallucinations may not
      simply be direct, but mediated by dissociative experiences, especially
      depersonalization. Clinical implications are also briefly discussed.

PMID- 22589016
TI  - The role of posttraumatic stress and problem alcohol involvement in university
      academic performance.
AB  - OBJECTIVE: The present study examines how Posttraumatic Stress Disorder (PTSD)
      during the first year of university affects academic performance and whether
      alcohol behavior mediates the relationship between PTSD and poor academic
      outcomes. METHOD: University students (N = 1,002; 65% female; Mage = 18.11)
      completed a baseline web survey, and 5 subsequent surveys throughout freshman
      year assessing variables of interest. RESULTS: Mediation analyses were not
      significant; however, students who developed PTSD had a lower grade point average
      and experienced more alcohol consequences by the end of freshman year. Unremitted
      PTSD and alcohol consequences were associated with leaving university by year's
      end. CONCLUSIONS: Findings suggest that assessment of trauma-related symptoms and
      alcohol behavior might benefit interventions aimed at students with academic
      difficulties.

PMID- 22589018
TI  - Reduction of skin closure time without loss of healing quality: a multicenter
      prospective study in 100 patients comparing the use of Insorb absorbable staples
      with absorbable thread for dermal suture.
AB  - The authors report the results of a multicenter prospective study evaluating a
      novel technology: dermal suture using absorbable staples composed of polylactic
      and polyglycolic acids. From January to June 2009, 59 dermal sutures were
      performed with Insorb absorbable staples and 41 with absorbable thread. All
      patients in the study underwent abdominal dermolipectomy (N = 65) or surgery for
      breast hypertrophy (N = 35). The purpose of the study was to compare the closure
      time and healing quality obtained with the 2 methods. Ninety-five patients were
      reexamined by the surgeon after 1 year of follow-up to assess scar width,
      suppleness, inflammation, and hypertrophy. The overall results were good and
      quite similar for the 2 groups. Thus, the use of Insorb staples reduced closure
      time while ensuring good healing quality.

PMID- 22589017
TI  - The use of multimedia consent programs for surgical procedures: a systematic
      review.
AB  - OBJECTIVE: To compare multimedia and standard consent, in respect to patient
      comprehension, anxiety, and satisfaction, for various surgical/interventional
      procedures. DATA SOURCES: Electronic searches of PubMed, MEDLINE, Ovid, Embase,
      and Google Scholar were performed. Relevant articles were assessed by 2
      independent reviewers. STUDY SELECTION: Comparative (randomized and nonrandomized
      control trials) studies of multimedia and standard consent for a variety of
      surgical/interventional procedures were included. Studies had to report on at
      least one of the outcome measures. DATA EXTRACTION: Studies were reviewed by 2
      independent investigators. The first investigator extracted all relevant data,
      and consensus of each extraction was performed by a second investigator to verify
      the data. CONCLUSION: Overall, this review suggests that the use of multimedia as
      an adjunct to conventional consent appears to improve patient comprehension.
      Multimedia leads to high patient satisfaction in terms of feasibility, ease of
      use, and availability of information. There is no conclusive evidence
      demonstrating a significant reduction in preoperative anxiety.

PMID- 22589019
TI  - The use of the harmonic scalpel versus knot tying for modified radical neck
      dissection.
AB  - BACKGROUND: Although the utility of the harmonic scalpel (HS) in thyroidectomy
      has been extensively demonstrated, there is little experience regarding its use
      for neck dissections. METHODS: Within 10 years, 119 patients underwent modified
      radical neck dissection (MRND) for thyroid cancer. In 51 patients, MRND was
      performed using conventional knot tying and in 68 using the HS. The number of
      lymph nodes (LNs) removed, operative time, estimated blood loss (EBL), drain
      output, duration of the drainage, and complications were compared for 47 patients
      undergoing first-time unilateral MRND without concomitant additional surgical
      procedures. RESULTS: The number of LNs removed, operative time, duration of
      drainage, and rate of lymphatic leak were similar between groups. For the HS
      group, EBL (5 +/- 3 vs 32 +/- 10; P = .006) and drain output on postoperative day
      1 (51.7 +/- 6.2 vs 78.9 +/- 11.9; P = .02) and at 1 week (6.1 +/- 1.2 vs 10.2 +/-
      1.8, respectively; P = .03) were significantly less. CONCLUSION: Despite the
      limitations of its retrospective nature, this study shows that the HS reduces EBL
      and the amount of lymphatic drainage compared to knot tying after MRND.

PMID- 22589020
TI  - Single-incision laparoscopic hepaticojejunostomy using conventional instruments
      for neonates with extrahepatic biliary cystic lesions.
AB  - BACKGROUND: Single-incision laparoscopic surgery has been increasingly adopted in
      pediatric surgery. Nevertheless, its feasibility and safety in neonates with
      congenital biliary malformations is unclear. This study reports successful single
      incision laparoscopic hepaticojejunostomy (SILH) for neonates with extrahepatic
      biliary cystic lesions. METHODS: Ten neonates with extrahepatic biliary cystic
      lesions (choledochal cyst/correctable biliary atresia: 6/4) who underwent SILH
      between May 2011 and September 2011 were reviewed. Ultrasonography, upper
      gastrointestinal contrast studies, and laboratory tests were performed during the
      follow-up period. RESULTS: Mean operative time, postoperative hospital stay, time
      to full feeding, and duration of drainage were comparable to our historic open
      control groups of 15 neonates with choledochal cysts and 7 patients with
      correctable biliary atresia. Median follow-up duration was 6.0 months. They
      regularly took medical treatments during the follow-up periods. The jaundice
      subsided or liver function was normalized within 3 months postoperatively. So
      far, no mortality or morbidity of cholangitis, bile leak, anastomotic stenosis,
      and intrahepatic reflux were encountered. CONCLUSIONS: In experienced hands, SILH
      for neonates with extrahepatic biliary cystic lesions is feasible and safe. It
      provides a new alternative for neonatal hepatobiliary surgery.

PMID- 22589022
TI  - Polymer/boron nitride nanocomposite materials for superior thermal transport
      performance.
AB  - Boron nitride nanosheets were dispersed in polymers to give composite films with
      excellent thermal transport performances approaching the record values found in
      polymer/graphene nanocomposites. Similarly high performance at lower BN loadings
      was achieved by aligning the nanosheets in poly(vinyl alcohol) matrix by simple
      mechanical stretching (see picture).

PMID- 22589021
TI  - Role and potential mechanisms of anabolic resistance in sarcopenia.
AB  - There is pressing need to understand the aging process to better cope with its
      associated physical and societal costs. The age-related muscle wasting known as
      sarcopenia is a major contributor to the problems faced by the elderly. By
      hindering mobility and reducing strength, it greatly diminishes independence and
      quality of life. In studying the factors that contribute to the development of
      sarcopenia, the focus is shifting to the study of disordered muscle anabolism.
      The abnormal response of muscle to previously well-established anabolic stimuli
      is known as anabolic resistance, and may be a key factor in the development and
      progression of sarcopenia. Factors such as age, obesity, inflammation, and
      lipotoxicity contribute to anabolic resistance, and have been studied either
      directly or indirectly in cell systems and whole animals. Understanding the
      physiologic and mechanistic basis of anabolic resistance could be the key to
      formulating new and targeted interventions that would ease the burden currently
      borne by the world's aged population.

PMID- 22589023
TI  - "You need a song to bring you through": the use of religious songs to manage
      stressful life events.
AB  - PURPOSE: To explore in a sample of older African Americans how religious songs
      were used to cope with stressful life events and to explore the religious beliefs
      associated with these songs. DESIGN AND METHODS: Sixty-five African American
      older adults residing in the Southeastern US participated in a qualitative
      descriptive study involving criterion sampling, open-ended semi-structured
      interviews, qualitative content analysis, and descriptive statistics. RESULTS:
      Religion expressed through song was a coping strategy for participants
      experiencing stressful life events who described feelings of being comforted,
      strengthened, able to endure, uplifted, and able to find peace by turning to the
      types of religious songs described here. Five types of songs were used including
      those evoking Thanksgiving and Praise, Instructive, Memory of Forefathers,
      Communication with God, and Life after Death. IMPLICATIONS: Religious songs are
      an important form of religious expression important to the mental health of older
      African Americans. The incorporation of religious songs into spiritual care
      interventions might enhance the cultural relevance of mental health interventions
      in this population.

PMID- 22589024
TI  - Holding abusers accountable: an elder abuse forensic center increases criminal
      prosecution of financial exploitation.
AB  - PURPOSE: Despite growing awareness of elder abuse, cases are rarely prosecuted.
      The aim of this study was to examine the effectiveness of an elder abuse forensic
      center compared with usual care to increase prosecution of elder financial abuse.
      DESIGN AND METHODS: Using one-to-one propensity score matching, cases referred to
      the Los Angeles County Elder Abuse Forensic Center (the Forensic Center) between
      April 2007 and December 2009 for financial exploitation of adults aged 65 and
      older (n = 237) were matched to a population of 33,650 cases that received usual
      care from Adult Protective Services (APS). RESULTS: 1 Significantly, more
      Forensic Center cases were submitted to the District Attorney's office (DA) for
      review (22%, n = 51 vs. 3%, n = 7 usual care, p < .001). Among the cases
      submitted, charges were filed by the DA at similar rates, as was the proportion
      of resultant pleas and convictions. Using logistic regression, the strongest
      predictor of case review and ultimate filing and conviction was whether the case
      was presented at the Forensic Center, with 10 times greater odds of submission to
      the DA (Odds ratio = 11.00, confidence interval = 4.66-25.98). IMPLICATIONS:
      Previous studies have not demonstrated that elder abuse interventions impact
      outcomes; this study breaks new ground by showing that an elder abuse
      multidisciplinary team increases rates of prosecution for financial exploitation.
      The elder abuse forensic center model facilitates cooperation and group problem
      solving among key professionals, including APS, law enforcement, and the DA and
      provides additional resources such as neuropsychological testing, medical record
      review, and direct access to the Office of the Public Guardian.

PMID- 22589025
TI  - Femtosecond laser microstructuring for polymeric lab-on-chips.
AB  - This paper provides an overview of femtosecond laser microfabrication in
      polymeric materials, with emphasis on lab-on-chip applications. Due to the
      nonlinear interaction of femtosecond laser pulses with polymers, laser-induced
      modifications are localized to the focal volume, enabling high resolution
      patterning in 3D. Femtosecond laser microfabrication offers unmatched versatility
      in fabricating surface microchannels and diffractive optics by means of laser
      ablation, buried optical waveguides and micro-optics through refractive index
      modification and complex 3D microstructures in photoresists by two-photon
      polymerization. Femtosecond laser microfabrication technology opens the door to
      fabricating integrated lab-on-chip devices with a single tool.

PMID- 22589026
TI  - A triphasic metacognitive formulation of problem drinking.
AB  - In this paper, a triphasic metacognitive formulation of problem drinking and its
      implications for treatment are presented together with a summary of the evidence
      consistent with this approach. In the triphasic formulation during the pre
      alcohol use phase, alcohol-related triggers, in the form of cravings, images,
      memories or thoughts, activate positive metacognitive beliefs about extended
      thinking, which lead to desire thinking, rumination and worry or their
      combination. The activation of the latter brings to an escalation of cravings and
      negative affect, strengthening negative metacognitive beliefs about the need to
      control thoughts and enhancing the likelihood of alcohol use. In the alcohol use
      phase, positive metacognitive beliefs about alcohol use and a reduction in
      metacognitive monitoring contribute to dysregulation in alcohol use. Over the
      course of time and as the drinking problem escalates in severity, negative
      metacognitive beliefs about the uncontrollability of alcohol use and alcohol
      related thoughts emerge, contributing to the perseveration of dysregulated
      alcohol use. In the post-alcohol use phase following the activation of positive
      metacognitive beliefs about post-event rumination, the affective, cognitive and
      physiological consequences of dysregulated alcohol use become the subject of
      rumination. This, in turn, leads to a paradoxical increase in negative affect and
      alcohol-related thoughts, together with the strengthening of negative
      metacognitive beliefs about such thoughts. Intermittent attempts to suppress
      alcohol-related thoughts increase the likelihood of returning to use alcohol as a
      means of achieving self-regulation. KEY PRACTITIONER MESSAGE: A metacognitive
      formulation of problem drinking that may aid assessment, conceptualization and
      treatment across the problem drinking spectrum.

PMID- 22589028
TI  - Evaluating the causes of lameness in horses.

PMID- 22589027
TI  - VDC calls for more engagement with the business of farming.

PMID- 22589029
TI  - Bovine TB: controls on cattle to be strengthened in England.

PMID- 22589030
TI  - Tackling abuse in animals and people.

PMID- 22589033
TI  - Meeting the costs of initial emergency treatment.

PMID- 22589034
TI  - New codes of conduct for vets and veterinary nurses.

PMID- 22589035
TI  - The extent and implications of unwanted cats and dogs.

PMID- 22589036
TI  - Number of cats and dogs in UK welfare organisations.
AB  - It is not known how many cats and dogs are admitted to welfare organisations
      annually. This study produced the first estimates of the size of this population.
      A questionnaire was mailed out to welfare organisations during 2010, followed by
      a postal/email reminder and requests to non-responders for a telephone interview.
      The questionnaire covered areas including, the current number of cats and dogs
      being housed, how much of the year organisations were operating at full capacity
      as well as the number of cats and dogs admitted, rehomed and euthanased between
      January and December 2009. Responses were obtained from 54.8 per cent of
      organisations. Sixty-six per cent of cat welfare organisations and 48 per cent of
      dog welfare organisations reported that they operated at full capacity for 12
      months of the year. The number of cats and dogs entering UK welfare organisations
      during 2009 was estimated as 131,070 and 129,743, respectively. This highlights
      the scale of the work performed by welfare organisations in caring for and
      rehoming unwanted cats and dogs annually and emphasises the urgent need to
      address concerns over the considerable number of these animals. This study has
      also produced useful baseline data, which will be essential for monitoring
      population changes over time.

PMID- 22589037
TI  - Periweaning failure to thrive in pigs in Spain.

PMID- 22589038
TI  - RCVS overspend review group.

PMID- 22589039
TI  - Modernising meat inspection.

PMID- 22589040
TI  - Do SE(II) electrons really degrade SEM image quality?
AB  - Generally, in scanning electron microscopy (SEM) imaging, it is desirable that a
      high-resolution image be composed mainly of those secondary electrons (SEs)
      generated by the primary electron beam, denoted SE(I) . However, in conventional
      SEM imaging, other, often unwanted, signal components consisting of backscattered
      electrons (BSEs), and their associated SEs, denoted SE(II) , are present; these
      signal components contribute a random background signal that degrades contrast,
      and therefore signal-to-noise ratio and resolution. Ideally, the highest
      resolution SEM image would consist only of the SE(I) component. In SEMs that use
      conventional pinhole lenses and their associated Everhart-Thornley detectors, the
      image is composed of several components, including SE(I) , SE(II) , and some BSE,
      depending on the geometry of the detector. Modern snorkel lens systems eliminate
      the BSEs, but not the SE(II) s. We present a microfabricated diaphragm for
      minimizing the unwanted SE(II) signal components. We present evidence of improved
      imaging using a microlithographically generated pattern of Au, about 500 nm
      thick, that blocks most of the undesired signal components, leaving an image
      composed mostly of SE(I) s. We refer to this structure as a "spatial backscatter
      diaphragm."

PMID- 22589041
TI  - Click ionic liquids: a family of promising tunable solvents and application in
      Suzuki-Miyaura cross-coupling.
AB  - A series of click ionic salts 4 a-4 n was prepared through click reaction of
      organic azides with alkyne-functionalized imidazolium or 2-methylimidazolium
      salts, followed by metathesis with lithium bis(trifluoromethanesulfonyl)amide or
      potassium hexafluorophosphate. All salts were characterized by IR, NMR, TGA, and
      DSC, and most of them can be classified as ionic liquids. Their steric and
      electronic properties can be easily tuned and modified through variation of the
      aromatic or aliphatic substituents at the imidazolium and/or triazolyl rings. The
      effect of anions and substituents at the two rings on the physicochemical
      properties was investigated. The charge and orbital distributions based on the
      optimized structures of cations in the salts were calculated. Reaction of 4 a
      with PdCl(2)  produced mononuclear click complex 4 a-Pd, the structure of which
      was confirmed by single-crystal X-ray diffraction analysis. Suzuki-Miyaura cross
      coupling shows good catalytic stability and high recyclability in the presence of
      PdCl(2)  in 4 a. TEM and XPS analyses show formation of palladium nanoparticles
      after the reaction. The palladium NPs in 4 a are immobilized by the synergetic
      effect of coordination and electrostatic interactions with 1,2,3-triazolyl and
      imidazolium, respectively.

PMID- 22589043
TI  - Child maltreatment--clinical PTSD diagnosis not enough?!: Comment on Resick et
      al. (2012).
AB  - Child maltreatment has a high prevalence. It can lead to severe psychological and
      physical problems from childhood to late adulthood. At present, the recognition
      and treatment of child abuse and its consequences is inadequate. Diagnostic
      criteria, such as those defined in the Diagnostic and Statistical Manual of
      Mental Disorders of the American Psychiatric Association, are vital for that
      purpose. Resick and colleagues (2012) conclude that insufficient scientific basis
      now exists for incorporating complex posttraumatic stress disorder (CPTSD) into
      DSM-5. Although they are right from a research point of view, what would be the
      clinical, political, and social consequences of not including it? This comment
      discusses those consequences from the standpoint that treating children with
      developmental trauma disorder at an early age will serve to prevent later
      sequelae.

PMID- 22589042
TI  - Impact of safety monitoring on error probabilities of binary efficacy outcome
      analyses in large phase III group sequential trials.
AB  - In phase III clinical trials, some adverse events may not be rare or unexpected
      and can be considered as a primary measure for safety, particularly in trials of
      life-threatening conditions, such as stroke or traumatic brain injury. In some
      clinical areas, efficacy endpoints may be highly correlated with safety
      endpoints, yet the interim efficacy analyses under group sequential designs
      usually do not consider safety measures formally in the analyses. Furthermore,
      safety is often statistically monitored more frequently than efficacy measures.
      Because early termination of a trial in this situation can be triggered by either
      efficacy or safety, the impact of safety monitoring on the error probabilities of
      efficacy analyses may be nontrivial if the original design does not take the
      multiplicity effect into account. We estimate the actual error probabilities for
      a bivariate binary efficacy-safety response in large confirmatory group
      sequential trials. The estimated probabilities are verified by Monte Carlo
      simulation. Our findings suggest that type I error for efficacy analyses
      decreases as efficacy-safety correlation or between-group difference in the
      safety event rate increases. In addition, although power for efficacy is robust
      to misspecification of the efficacy-safety correlation, it decreases dramatically
      as between-group difference in the safety event rate increases.

PMID- 22589044
TI  - Comparative stability studies of poly(2-methyl-2-oxazoline) and poly(ethylene
      glycol) brush coatings.
AB  - Non-fouling surfaces that resist non-specific adsorption of proteins, bacteria,
      and higher organisms are of particular interest in diverse applications ranging
      from marine coatings to diagnostic devices and biomedical implants. Poly(ethylene
      glycol) (PEG) is the most frequently used polymer to impart surfaces with such
      non-fouling properties. Nevertheless, limitations in PEG stability have
      stimulated research on alternative polymers that are potentially more stable than
      PEG. Among them, we previously investigated poly(2-methyl-2-oxazoline) (PMOXA), a
      peptidomimetic polymer, and found that PMOXA shows excellent anti-fouling
      properties. Here, we compare the stability of films self-assembled from graft
      copolymers exposing a dense brush layer of PEG and PMOXA side chains,
      respectively, in physiological and oxidative media. Before media exposure both
      film types prevented the adsorption of full serum proteins to below the detection
      limit of optical waveguide in situ measurements. Before and after media exposure
      for up to 2 weeks, the total film thickness, chemical composition, and total
      adsorbed mass of the films were quantified using variable angle spectroscopic
      ellipsometry (VASE), X-ray photoelectron spectroscopy (XPS), and optical
      waveguide lightmode spectroscopy (OWLS), respectively. We found (i) that PMOXA
      graft copolymer films were significantly more stable than PEG graft copolymer
      films and kept their protein-repellent properties under all investigated
      conditions and (ii) that film degradation was due to side chain degradation
      rather than due to copolymer desorption.

PMID- 22589045
TI  - Self-assembled peptides: characterisation and in vivo response.
AB  - The fabrication of tissue engineering scaffolds is a well-established field that
      has gained recent prominence for the in vivo repair of a variety of tissue types.
      Recently, increasing levels of sophistication have been engineered into adjuvant
      scaffolds facilitating the concomitant presentation of a variety of stimuli (both
      physical and biochemical) to create a range of favourable cellular
      microenvironments. It is here that self-assembling peptide scaffolds have shown
      considerable promise as functional biomaterials, as they are not only formed from
      peptides that are physiologically relevant, but through molecular recognition can
      offer synergy between the presentation of biochemical and physio-chemical cues.
      This is achieved through the utilisation of a unique, highly ordered, nano- to
      microscale 3-D morphology to deliver mechanical and topographical properties to
      improve, augment or replace physiological function. Here, we will review the
      structures and forces underpinning the formation of self-assembling scaffolds,
      and their application in vivo for a variety of tissue types.

PMID- 22589046
TI  - Alkylation of spiropyran moiety provides reversible photo-control over
      nanostructured soft materials.
AB  - The purpose of this study was to create a light responsive nanostructured liquid
      crystalline matrix using a novel alkylated spiropyran photochromic molecule
      (spiropyran laurate, SPL) as a light activated drug delivery system. The liquid
      crystal matrix, prepared from phytantriol, responds reversibly to changes in
      photoisomerism of SPL on irradiation, switching between the bicontinuous cubic
      and the reversed hexagonal liquid crystal structures, a change previously shown
      to dramatically alter drug release rate. In contrast, the non-derivatized
      spiropyran and spirooxazine photochromic compounds do not sufficiently disrupt
      the matrix on isomerization to induce the phase change. Thus, novel alkylated
      spiropyran has the potential to be an effective agent for use in liquid
      crystalline systems for reversible 'on-demand' drug delivery applications.

PMID- 22589047
TI  - Understanding nano-anatomy of healthy and carious human teeth: a prerequisite for
      nanodentistry.
AB  - The anatomy of human teeth reflects its usage. Spatially resolved X-ray
      scattering permits quantitative studies of the characteristic arrangement of the
      anisotropic calcium phosphate crystallites and the collagen fibers within the
      hard tissues of the crown. The present study summarizes the distinctive nanometer
      sized anatomical features of the tooth hard tissues including their interface
      taking advantage of spatially resolved synchrotron radiation-based small-angle X
      ray scattering. The comparison of slices from eight teeth indicates a long-range
      organization of tooth nanostructures.

PMID- 22589048
TI  - Nano-sized albumin-copolymer micelles for efficient doxorubicin delivery.
AB  - We present the discovery of a nano-sized protein-derived micellar drug delivery
      system based on the polycationic albumin precursor protein cBSA-147. The
      anticancer drug doxorubicin (DOX) was efficiently encapsulated into nanosized
      micelles based on hydrophobic interactions with the polypeptide scaffold. These
      micelles revealed attractive stabilities in various physiological buffers and a
      wide pH range as well as very efficient uptake into A549 cells after 1 h
      incubation time only. In vitro cytotoxicity was five-times increased compared to
      free DOX also indicating efficient intracellular drug release. In addition,
      multiple functional groups are available for further chemical modifications.
      Based on the hydrophobic loading mechanism, various classical anti-cancer drugs,
      in principle, could be delivered even synergistically in a single micelle.
      Considering these aspects, this denatured albumin-based drug delivery system
      represents a highly attractive platform for nanomedicine approaches towards
      cancer therapy.

PMID- 22589049
TI  - Nano-mechanical transduction of polymer micro-cantilevers to detect bio-molecular
      interactions.
AB  - Using variothermal polymer micro-injection molding, disposable arrays of eight
      polymer micro-cantilevers each 500 MUm long, 100 MUm wide and 25 MUm thick were
      fabricated. The present study took advantage of an easy flow grade polypropylene.
      After gold coating for optical read-out and asymmetrical sensitization, the
      arrays were introduced into the Cantisens((r)) Research system to perform
      mechanical and functional testing. We demonstrate that polypropylene cantilevers
      can be used as biosensors for medical purposes in the same manner as the
      established silicon ones to detect single-stranded DNA sequences and metal ions
      in real-time. A differential signal of 7 nm was detected for the hybridization of
      1 MUM complementary DNA sequences. For 100 nM copper ions the differential signal
      was found to be (36 +/- 5) nm. Nano-mechanical sensing of medically relevant,
      nanometer-size species is essential for fast and efficient diagnosis.

PMID- 22589050
TI  - Design and preparation of a nanoprobe for imaging inflammation sites.
AB  - To image inflammation sites, we developed a novel nanoparticle, hydroxylamine
      containing nanoparticle (HANP), which emits an intense electron spin resonance
      (ESR)-signal triggered by enzymatic oxidation reaction and pH-sensitive self
      disintegration. The nanoparticle was prepared from an amphiphilic block
      copolymer, poly(ethylene glycol)-b-poly[4-(2,2,6,6-tetramethylpiperidine-1
      hydroxyl)aminomethylstyrene] (PEG-b-PMNT-H), which spontaneously forms a core
      shell type polymeric micelle (particle diameter = ca. 50 nm) in aqueous media.
      Because the PMNT-H segment in the block copolymer possesses amino groups in each
      repeating unit, the particle can be disintegrated by protonation of the amino
      groups in an acidic pH environment such as inflammation sites, which is confined
      to the hydrophobic core of HANP. Mixing HANP with horseradish peroxidase
      (HRP)/H(2)O(2) mixture resulted in enzymatic oxidization of the hydroxylamines in
      the PEG-b-PMNT-H and converted the hydroxylamine to the stable nitroxide radical
      form in PEG-b-poly[4-(2,2,6,6-tetramethylpiperidine-1-oxyl)aminomethylstyrene]
      (PEG-b-PMNT), which shows an intense ESR signal. It is interesting to note that
      the ESR signal increased at a greater rate under acidic conditions (pH 5.6) than
      that under neutral conditions (pH 7.4), although the enzymatic activity of HRP
      under neutral conditions is known to be much higher than that under acidic
      conditions. This indicates that enzymatic oxidation reaction was accelerated by
      synchronizing the disintegration of HANP under acidic conditions. On the basis of
      these results, HANP can be used as a high-performance ESR probe for imaging of
      inflammation sites.

PMID- 22589051
TI  - Myoblast cell interaction with polydopamine coated liposomes.
AB  - Liposomes are widely used, from biosensing to drug delivery. Their coating with
      polymers for stability and functionalization purposes further broadens their set
      of relevant properties. Poly(dopamine) (PDA), a eumelanin-like material deposited
      via the "self"-oxidative polymerization of dopamine at mildly basic pH, has
      attracted considerable interest in the past few years due to its simplicity,
      flexibility yet fascinating properties. Herein, we characterize the coating of
      different types of liposomes with PDA depending on the presence of oleoyldopamine
      in the lipid bilayer and the dopamine hydrochloride concentration. Further, the
      interaction of these coated liposomes in comparison to their uncoated
      counterparts with myoblast cells is assessed. Their uptake/association efficiency
      with these cells is determined. Further, their dose-dependent cytotoxicity with
      and without entrapped hydrophobic cargo (thiocoraline) is characterized. Taken
      together, the reported results demonstrate the potential of PDA coated liposomes
      as a tool in biomedical applications.

PMID- 22589052
TI  - Stimuli-responsive polymers and their applications in nanomedicine.
AB  - This review focuses on smart nano-materials built of stimuli-responsive (SR)
      polymers and will discuss their numerous applications in the biomedical field.
      The authors will first provide an overview of different stimuli and their
      corresponding, responsive polymers. By introducing myriad functionalities, SR
      polymers present a wide range of possibilities in the design of stimuli
      responsive devices, making use of virtually all types of polymer constructs, from
      self-assembled structures (micelles, vesicles) to surfaces (polymer brushes,
      films) as described in the second section of the review. In the last section of
      this review the authors report on some of the most promising applications of
      stimuli-responsive polymers in nanomedicine. In particular, we will discuss
      applications pertaining to diagnosis, where SR polymers are used to construct
      sensors capable of selective recognition and quantification of analytes and
      physical variables, as well as imaging devices. We will also highlight some
      examples of responsive systems used for therapeutic applications, including smart
      drug delivery systems (micelles, vesicles, dendrimers...) and surfaces for
      regenerative medicine.

PMID- 22589054
TI  - Development of a platform of antibody-presenting liposomes.
AB  - Antibody-presenting liposomes present high interest as drug delivery systems. The
      association of antibodies to liposomes is usually realized by covalent coupling
      of IgGs or their antigen-binding fragments to lipid polar head groups by means of
      hetero-bifunctional crosslinkers. We present here an original platform of IgG
      presenting liposomes which is based on a fusion protein between Annexin-A5 (Anx5)
      and the IgG-binding ZZ repeat derived from Staphylococcus aureus protein A. The
      Anx5ZZ fusion protein acts as a bi-functional adaptor that anchors IgGs to
      liposomes in a non covalent and highly versatile manner. The interactions between
      IgGs, Anx5ZZ and liposomes were characterized by PAGE, dynamic light scattering
      and fluorescence quenching assays, establishing that binding of Anx5ZZ to IgGs
      and of Anx5ZZ-IgG complexes to liposomes is complete with stoichiometric amounts
      of each species. We found that the sequence of assembly is important and that
      Anx5ZZ-IgG complexes need to be formed first in solution and then adsorbed to
      liposomes in order to avoid aggregation. The targeting capacity of Anx5ZZ-IgG
      functionalized liposomes was demonstrated by electron microscopy on an ex vivo
      model system of atherosclerotic plaques. This study shows that the Anx5ZZ adaptor
      constitutes an efficient platform for functionalizing liposomes with IgGs. This
      platform may present potential applications in molecular imaging and drug
      delivery.

PMID- 22589053
TI  - Deciphering an underlying mechanism of differential cellular effects of
      nanoparticles: an example of Bach-1 dependent induction of HO-1 expression by
      gold nanorod.
AB  - Gold nanoparticles are extensively investigated for their potential biomedical
      applications. Therefore, it is pertinent to thoroughly evaluate their biological
      effects at different levels and their underlying molecular mechanism. Frequently,
      there are discrepancies about the biological effects of various gold
      nanoparticles among the reports dealing with different models. Most of the
      studies focused on the different biological effects of various nano-properties of
      the nanomaterials. We hypothesize that the biological models with different
      metabolic processes would be taken into account to explain the observed
      discrepancies of biological effects of nanomaterials. Herein, by using mouse
      embryo fibroblast cell line (MEF-1) and human embryonal lung fibroblast cell line
      (MRC-5) as in vitro models, we studied the cellular effects of gold nanorods
      (AuNRs) coated with poly (diallyldimethyl ammonium chloride) (PDDAC),
      polyethylene glycol and polystyrene sulfonae (PSS). We found that all three AuNRs
      had no effects on cellular viability at the concentration of 1 nM; however, AuNRs
      that coated with PDDAC and PSS induced significant up-regulation of heme
      oxygenase-1 (HO-1) which was believed to be involved in cellular defense
      activities in MEF-1 but not in MRC-5 cells. Further study showed that the low
      fundamental expression of transcription factor Bach-1, the major regulator of HO
      1 expression, in MEF-1 was responsible for the up-regulation of HO-1 induced by
      the AuNRs. Our results indicate that although AuNRs we used are non-cytotoxic,
      they cell-specifically induce change of gene expression, such as HO-1. Our
      current study provides a good example to explain the molecular mechanisms of
      differential biological effects of nanomaterials in different cellular models.
      This finding raises a concern on evaluation of cellular effects of nanoparticles
      where the cell models should be critically considered.

PMID- 22589055
TI  - The new (challenging) role of academia in biomaterial translational research and
      medical device development.
AB  - With the ever-changing landscape of translational research, the medical device
      and pharmaceutical industries increasingly license technologies with the added
      value of clinical and/or pre-clinical data rather than those in earlier stages of
      development. Universities have the potential to fill the gap in product
      development from academic laboratories through enhanced student training and
      increased implementation of some development and manufacturing activities that
      are traditionally found only in the private sector. A development roadmap is
      described from initial product feasibility through commercialization in the
      context of efficient development practices. The specific challenges in the design
      and development of biomaterial-based medical devices are described in the context
      of this development path with an emphasis on unique challenges for academic
      laboratories.

PMID- 22589056
TI  - Design and fabrication of tubular scaffolds via direct writing in a melt
      electrospinning mode.
AB  - Flexible tubular structures fabricated from solution electrospun fibers are
      finding increasing use in tissue engineering applications. However it is
      difficult to control the deposition of fibers due to the chaotic nature of the
      solution electrospinning jet. By using non-conductive polymer melts instead of
      polymer solutions the path and collection of the fiber becomes predictable. In
      this work we demonstrate the melt electrospinning of polycaprolactone in a direct
      writing mode onto a rotating cylinder. This allows the design and fabrication of
      tubes using 20 MUm diameter fibers with controllable micropatterns and mechanical
      properties. A key design parameter is the fiber winding angle, where it allows
      control over scaffold pore morphology (e.g. size, shape, number and porosity).
      Furthermore, the establishment of a finite element model as a predictive design
      tool is validated against mechanical testing results of melt electrospun tubes to
      show that a lesser winding angle provides improved mechanical response to
      uniaxial tension and compression. In addition, we show that melt electrospun
      tubes support the growth of three different cell types in vitro and are therefore
      promising scaffolds for tissue engineering applications.

PMID- 22589057
TI  - The role of enamel proteins in protecting mature human enamel against acidic
      environments: a double layer force spectroscopy study.
AB  - Characterisation of the electrostatic properties of dental enamel is important
      for understanding the interfacial processes that occur on a tooth surface and how
      these relate to the natural ability of our teeth to withstand chemical attack
      from the acids in many soft drinks. Whereas, the role of the mineral component of
      the tooth enamel in providing this resistance to acid erosion has been studied
      extensively, the influence of proteins that are also present within the structure
      is not well understood. In this paper, we report for the first time the use of
      double-layer force spectroscopy to directly measure electrostatic forces on as
      received and hydrazine-treated (deproteinated) enamel surfaces in solutions with
      different pH to determine how the enamel proteins influence acid erosion surface
      potential and surface charge of human dental enamel. The deproteination of the
      treated samples was confirmed by the loss of the amide bands (~1,300-1,700 cm(
      1)) in the FTIR spectrum of the sample. The force characteristics observed were
      found to agree with the theory of electrical double layer interaction under the
      assumption of constant potential and allowed the surface charge per unit area to
      be determined for the two enamel surfaces. The values and, importantly, the sign
      of these adsorbed surface charges indicates that the protein content of dental
      enamel contributes significantly to the electrostatic double layer formation near
      the tooth surface and in doing so can buffer the apatite crystals against acid
      attack. Moreover, the electrostatic interactions within this layer are a driving
      factor for the mineral transfer from the tooth surface and the initial salivary
      pellicle formation.

PMID- 22589059
TI  - Polyethylenimine-based amphiphilic core-shell nanoparticles: study of gene
      delivery and intracellular trafficking.
AB  - Amphiphilic core-shell nanoparticle, which is composed of a hydrophobic core and
      a branched polyethylenimine (PEI) shell, has been designed and synthesized as a
      novel gene delivery nanocarrier. In our previous study, we demonstrated that the
      core-shell nanoparticle was not only able to efficiently complex with plasmid DNA
      (pDNA) and protect it against enzymatic degradation, but also three times less
      cytotoxic, and threefold more efficient in gene transfection than branched 25 kDa
      PEI. This paper reports our further studies in the following three aspects: (1)
      the ability of the PEI-based nanoparticles to deliver gene in various mammalian
      cell lines; (2) intracellular distributions of the nanoparticles and their pDNA
      complexes in HeLa cells; and (3) incorporation of nuclear targeting agent into
      the nanoparticle/pDNA complexes to enhance the nuclear targeting ability. The PEI
      based nanoparticles were able to transfect both human and non-human cell lines
      and their transfection efficiencies were cell-dependent. Within our four tested
      cell lines (MCF-7, BEL 7404, C6 and CHO-K1), gene transfer using PEI-based core
      shell nanoparticles displayed gene expression levels comparable to, or even
      better than, the commercial LipofectamineTM 2000. Confocal laser scanning
      microscopy showed that the nanoparticles and their pDNA complexes were
      effectively internalized into the HeLa cells. The in vitro time series
      experiments illustrated that both the nanoparticle/pDNA complexes and PEI-based
      nanoparticles were distributed in the cytoplasmic region after transfection for
      10 and 60 min, respectively. Nuclear localization was also observed in both
      samples after transfection for 20 and 60 min, respectively. Incorporation of the
      high mobility group box 1 (HMGB1) protein for nuclear targeting has also been
      demonstrated with a simple approach: electrostatic complexation between the PEI
      based nanoparticles and HMGB1. In the in vitro transfection study in MCF-7 cells,
      the expression level of the firefly luciferase gene encoded by the pDNA increased
      remarkably by up to eightfold when the HMGB1 protein was incorporated into the
      nanoparticle/pDNA complexes. Our results demonstrate that the PEI-based core
      shell nanoparticles are promising nanocarriers for gene delivery.

PMID- 22589060
TI  - Dynamic cellular uptake of mixed-monolayer protected nanoparticles.
AB  - Nanoparticles (NPs) are gaining increasing attention for potential application in
      medicine; consequently, studying their interaction with cells is of central
      importance. We found that both ligand arrangement and composition on gold
      nanoparticles play a crucial role in their cellular internalization. In our
      previous investigation, we showed that 66-34OT nanoparticles coated with stripe
      like domains of hydrophobic (octanethiol, OT, 34%) and hydrophilic (11
      mercaptoundecane sulfonate, MUS, 66%) ligands permeated through the cellular
      lipid bilayer via passive diffusion, in addition to endo-/pino-cytosis. Here, we
      show an analysis of NP internalization by DC2.4, 3T3, and HeLa cells at two
      temperatures and multiple time points. We study four NPs that differ in their
      surface structures and ligand compositions and report on their cellular
      internalization by intracellular fluorescence quantification. Using confocal
      laser scanning microscopy we have found that all three cell types internalize the
      66-34OT NPs more than particles coated only with MUS, or particles coated with a
      very similar coating but lacking any detectable ligand shell structure, or
      'striped' particles but with a different composition (34-66OT) at multiple data
      points.

PMID- 22589061
TI  - Model membrane platforms for biomedicine: case study on antiviral drug
      development.
AB  - As one of the most important interfaces in cellular systems, biological membranes
      have essential functions in many activities such as cellular protection and
      signaling. Beyond their direct functions, they also serve as scaffolds to support
      the association of proteins involved in structural support, adhesion, and
      transport. Unfortunately, biological processes sometimes malfunction and require
      therapeutic intervention. For those processes which occur within or upon
      membranes, it is oftentimes difficult to study the mechanism in a biologically
      relevant, membranous environment. Therefore, the identification of direct
      therapeutic targets is challenging. In order to overcome this barrier,
      engineering strategies offer a new approach to interrogate biological activities
      at membrane interfaces by analyzing them through the principles of the
      interfacial sciences. Since membranes are complex biological interfaces, the
      development of simplified model systems which mimic important properties of
      membranes can enable fundamental characterization of interaction parameters for
      such processes. We have selected the hepatitis C virus (HCV) as a model viral
      pathogen to demonstrate how model membrane platforms can aid antiviral drug
      discovery and development. Responsible for generating the genomic diversity that
      makes treating HCV infection so difficult, viral replication represents an ideal
      step in the virus life cycle for therapeutic intervention. To target HCV genome
      replication, the interaction of viral proteins with model membrane platforms has
      served as a useful strategy for target identification and characterization. In
      this review article, we demonstrate how engineering approaches have led to the
      discovery of a new functional activity encoded within the HCV nonstructural 5A
      protein. Specifically, its N-terminal amphipathic, alpha-helix (AH) can rupture
      lipid vesicles in a size-dependent manner. While this activity has a number of
      exciting biotechnology and biomedical applications, arguably the most promising
      one is in antiviral medicine. Based on the similarities between lipid vesicles
      and the lipid envelopes of virus particles, experimental findings from model
      membrane platforms led to the prediction that a range of medically important
      viruses might be susceptible to rupturing treatment with synthetic AH peptide.
      This hypothesis was tested and validated by molecular virology studies. Broad
      spectrum antiviral activity of the AH peptide has been identified against HCV,
      HIV, herpes simplex virus, and dengue virus, and many more deadly pathogens. As a
      result, the AH peptide is the first in class of broad-spectrum, lipid envelope
      rupturing antiviral agents, and has entered the drug pipeline. In summary,
      engineering strategies break down complex biological systems into simplified
      biomimetic models that recapitulate the most important parameters. This approach
      is particularly advantageous for membrane-associated biological processes because
      model membrane platforms provide more direct characterization of target
      interactions than is possible with other methods. Consequently, model membrane
      platforms hold great promise for solving important biomedical problems and
      speeding up the translation of biological knowledge into clinical applications.

PMID- 22589062
TI  - Nanomedicine in focus: opportunities and challenges ahead.

PMID- 22589063
TI  - No ice-like water at aqueous biological interfaces.
AB  - The surface vibrational spectrum of water at biological interfaces is often
      interpreted as having 'ice-like' and 'liquid-like' components. Here we show that
      the vibrational spectrum of water at both water-lipid and water-protein
      interfaces greatly simplifies upon H/D isotopic dilution, which is inconsistent
      with the presence of 'ice-like' structures. The changes in the spectra as a
      function of isotope content can be explained by intramolecular coupling between
      bend and stretch vibrations of the water molecules.

PMID- 22589064
TI  - Proliferation of epithelial cells on PDMS substrates with micropillars fabricated
      with different curvature characteristics.
AB  - The present work studied the proliferation of epithelial cells when they were
      cultivated on substrates with micropillars fabricated with the same height but
      with different curvature characteristics. A special micro-fabrication method was
      employed to produce these micropillar substrates. Polyallyldiglycol carbonate
      (PADC) films were first irradiated by alpha particles and then chemically etched
      to reach or beyond the "transition" phase to form casts with micrometer-sized
      pits with the same depth, but with different size and shape. Polydimethylsiloxane
      (PDMS) replicas of these PADC films then gave the desired substrates with
      micropillars with the same height but with different curvature characteristics.
      The micropillars on the PDMS substrates were found to be capable of changing the
      response of HeLa cells in terms of the percentages of cells in the S-phase and
      the attached cell numbers after 3-day cell culture. This demonstrated that the
      proliferation of the HeLa cells could be changed through mechanosensing the
      substrate curvature.

PMID- 22589065
TI  - Oriented, multimeric biointerfaces of the L1 cell adhesion molecule: an approach
      to enhance neuronal and neural stem cell functions on 2-D and 3-D polymer
      substrates.
AB  - This article focuses on elucidating the key presentation features of neurotrophic
      ligands at polymer interfaces. Different biointerfacial configurations of the
      human neural cell adhesion molecule L1 were established on two-dimensional films
      and three-dimensional fibrous scaffolds of synthetic tyrosine-derived
      polycarbonate polymers and probed for surface concentrations, microscale
      organization, and effects on cultured primary neurons and neural stem cells.
      Underlying polymer substrates were modified with varying combinations of protein
      A and poly-D-lysine to modulate the immobilization and presentation of the Fc
      fusion fragment of the extracellular domain of L1 (L1-Fc). When presented as an
      oriented and multimeric configuration from protein A-pretreated polymers, L1-Fc
      significantly increased neurite outgrowth of rodent spinal cord neurons and
      cerebellar neurons as early as 24 h compared to the traditional presentation via
      adsorption onto surfaces treated with poly-D-lysine. Cultures of human neural
      progenitor cells screened on the L1-Fc/polymer biointerfaces showed significantly
      enhanced neuronal differentiation and neuritogenesis on all protein A oriented
      substrates. Notably, the highest degree of betaIII-tubulin expression for cells
      in 3-D fibrous scaffolds were observed in protein A oriented substrates with PDL
      pretreatment, suggesting combined effects of cell attachment to polycationic
      charged substrates with subcellular topography along with L1-mediated adhesion
      mediating neuronal differentiation. Together, these findings highlight the
      promise of displays of multimeric neural adhesion ligands via biointerfacially
      engineered substrates to "cooperatively" enhance neuronal phenotypes on polymers
      of relevance to tissue engineering.

PMID- 22589066
TI  - Regulation of integrin adhesions by varying the density of substrate-bound
      epidermal growth factor.
AB  - Substrates coated with specific bioactive ligands are important for tissue
      engineering, enabling the local presentation of extracellular stimulants at
      controlled positions and densities. In this study, we examined the cross-talk
      between integrin and epidermal growth factor (EGF) receptors following their
      interaction with surface-immobilized Arg-Gly-Asp (RGD) and EGF ligands,
      respectively. Surfaces of glass coverslips, modified with biotinylated silane
      polyethylene glycol, were functionalized by either biotinylated RGD or EGF (or
      both) via the biotin-NeutrAvidin interaction. Fluorescent labeling of the
      adhering A431 epidermoid carcinoma cells for zyxin or actin indicated that EGF
      had a dual effect on focal adhesions (FA) and stress fibers: at low
      concentrations (0.1; 1 ng/ml), it stimulated their growth; whereas at higher
      concentrations, on surfaces with low to intermediate RGD densities, it induced
      their disassembly, leading to cell detachment. The EGF-dependent dissociation of
      FAs was, however, attenuated on higher RGD density surfaces. Simultaneous
      stimulation by both immobilized RGD and EGF suggest a strong synergy between
      integrin and EGFR signaling, in FA induction and cell spreading. A critical
      threshold level of EGF was required to induce significant variation in cell
      adhesion; beyond this critical density, the immobilized molecule had a
      considerably stronger effect on cell adhesion than did soluble EGF. The
      mechanisms underlying this synergy between the adhesion ligand and EGF are
      discussed.

PMID- 22589067
TI  - Comparison between empirical protein force fields for the simulation of the
      adsorption behavior of structured LK peptides on functionalized surfaces.
AB  - All-atom empirical molecular mechanics protein force fields, which have been
      developed to represent the energetics of peptide folding behavior in aqueous
      solution, have not been parameterized for protein interactions with solid
      material surfaces. As a result, their applicability for representing the
      adsorption behavior of proteins with functionalized material surfaces should not
      be assumed. To address this issue, we conducted replica-exchange molecular
      dynamics simulations of the adsorption behavior of structured peptides to
      functionalized surfaces using three protein force fields that are widely used for
      the simulation of peptide adsorption behavior: CHARMM22, AMBER94, and OPLS-AA.
      Simulation results for peptide structure both in solution and when adsorbed to
      the surfaces were compared to experimental results for similar peptide-surface
      systems to provide a means of evaluating and comparing the performance of these
      three force fields for this type of application. Substantial differences in both
      solution and adsorbed peptide conformations were found amongst these three force
      fields, with the CHARMM22 force field found to most closely match experimental
      results.

PMID- 22589069
TI  - Microfluidic assay to quantify the adhesion of marine bacteria.
AB  - For both, environmental and medical applications, the quantification of bacterial
      adhesion is of major importance to understand and support the development of new
      materials. For marine applications, the demand is driven by the quest for
      improved fouling-release coatings. To determine the attachment strength of
      bacteria to coatings, a microfluidic adhesion assay has been developed which
      allows probing at which critical wall shear stress bacteria are removed from the
      surface. Besides the experimental setup and the optimization of the assay, we
      measured adhesion of the marine bacterium Cobetia marina on a series of
      differently terminated self-assembled monolayers. The results showed that the
      adhesion strength of C. marina changes with surface chemistry. The difference in
      critical shear stress needed to remove bacteria can vary by more than one order
      of magnitude if a hydrophobic material is compared to an inert chemistry such as
      polyethylene glycol.

PMID- 22589068
TI  - Characterization of methacrylated type-I collagen as a dynamic, photoactive
      hydrogel.
AB  - Type-I collagen is an attractive scaffold material for tissue engineering due to
      its ability to self-assemble into a fibrillar hydrogel, its innate support of
      tissue cells through bioactive adhesion sites, and its biodegradability. However,
      a lack of control of material properties has hampered its utility as a scaffold.
      We have modified collagen via the addition of methacrylate groups to create
      collagen methacrylamide (CMA) using a synthesis reaction that allows retention of
      fundamental characteristics of native collagen, including spontaneous fibrillar
      self-assembly and enzymatic biodegradability. This method allows for a rapid,
      five-fold increase in storage modulus upon irradiation with 365 nm light.
      Fibrillar diameter of CMA was not significantly different from native collagen.
      Collagenolytic degradability of uncrosslinked CMA was minimally reduced, while
      photocrosslinked CMA was significantly more resistant to degradation. Live/Dead
      staining demonstrated that a large majority (71%) of encapsulated mesenchymal
      stem cells remained viable 24 h after photocrosslinking, which further increased
      to 81% after 72 h. This material represents a novel platform for creating
      mechanically heterogeneous environments.

PMID- 22589070
TI  - Effect of titanium surface calcium and magnesium on adhesive activity of
      epithelial-like cells and fibroblasts.
AB  - In the present study, we investigated the hydrothermal treatment of titanium with
      divalent cation solutions and its effect in promoting the adhesion of gingival
      epithelial cells and fibroblasts in vitro. Gingival keratinocyte-like Sa3 cells
      or fibroblastic NIH3T3 cells were cultured for 1 h on experimental titanium
      plates hydrothermally-treated with CaCl(2) (Ca) or MgCl(2) (Mg) solution, or
      distilled water (DW). The number and adhesive strengths of attached cells on the
      substrata were then analyzed. The number of Sa3 cells adhering to the Ca- and Mg
      treated plates was significantly larger than in the DW group, but the strength of
      this adhesion did not differ significantly between groups. In contrast, NIH3T3
      cell adhesion number and strength were increased in both the Ca and Mg groups
      compared to the DW group. Fluorescent microscopic observation indicated that, in
      all groups, Sa3 had identical expression levels of integrin beta4 and development
      of actin filaments, whereas NIH3T3 cells in the Ca and Mg groups displayed much
      stronger punctate cytoplasmic signals for vinculin and more bundle-shaped actin
      filaments than cells in the DW group. As a result, it was indicated that the
      hydrothermal treatment of titanium with Ca or Mg solution improved the
      integration of soft tissue cells with the substrata, which may facilitate the
      development of a soft tissue barrier around the implant.

PMID- 22589071
TI  - Platelet activation profiles on TiO2: effect of Ca2+ binding to the surface.
AB  - Surface ion equilibrium is hypothesized to play an important role in defining the
      interactions between foreign materials and biological systems. In this study, we
      compare two surfaces with respect to their ability to activate adhering
      platelets. One is a commonly used implant material TiO(2), which binds Ca(2+),
      and the other one is glass, which does not. We show, that in the presence of
      Ca(2+), TiO(2) acts as an agonist, activating adhering platelets and causing the
      expression on their surface of two well-known activation markers, CD62P (P
      selectin) and CD63. On the contrary, in the absence of Ca(2+), platelets adhering
      on TiO(2) express only one of the two markers, CD63. Platelets adhering on glass,
      as well as platelets challenged with soluble agonists in solution, express both
      markers independently of whether Ca(2+) is present or not. The expression of
      CD62P and CD63 is indicative of the exocytosis of the so-called alpha- and dense
      granules, respectively. It is a normal response of platelets to activation.
      Differences in the expression profiles of these two markers point to differential
      regulation of the exocytosis of the two kinds of granules, confirming the recent
      notion that platelets can tune their microenvironment in a trigger-specific
      fashion.

PMID- 22589072
TI  - Surface coating as a key parameter in engineering neuronal network structures in
      vitro.
AB  - By quantitatively comparing a variety of macromolecular surface coating agents,
      we discovered that surface coating strongly modulates the adhesion and
      morphogenesis of primary hippocampal neurons and serves as a switch of somata
      clustering and neurite fasciculation in vitro. The kinetics of neuronal adhesion
      on poly-lysine-coated surfaces is much faster than that on laminin and Matrigel
      coated surfaces, and the distribution of adhesion is more homogenous on poly
      lysine. Matrigel and laminin, on the other hand, facilitate neuritogenesis more
      than poly-lysine does. Eventually, on Matrigel-coated surfaces of self-assembled
      monolayers, neurons tend to undergo somata clustering and neurite fasciculation.
      By replacing coating proteins with cerebral astrocytes, and patterning neurons on
      astrocytes through self-assembled monolayers, microfluidics and micro-contact
      printing, we found that astrocyte promotes soma adhesion and astrocyte processes
      guide neurites. There, astrocytes could be a versatile substrate in engineering
      neuronal networks in vitro. Besides, quantitative measurements of cellular
      responses on various coatings would be valuable information for the neurobiology
      community in the choice of the most appropriate coating strategy.

PMID- 22589073
TI  - Immobilization of gelatin onto poly(glycidyl methacrylate)-grafted
      polycaprolactone substrates for improved cell-material interactions.
AB  - To enhance the cytocompatibility of polycaprolactone (PCL), cell-adhesive gelatin
      is covalently immobilized onto the PCL film surface via two surface-modified
      approaches: a conventional chemical immobilization process and a surface
      initiated atom transfer radical polymerization (ATRP) process. Kinetics studies
      reveal that the polymer chain growth from the PCL film using the ATRP process is
      formed in a controlled manner, and that the amount of immobilized gelatin
      increases with an increasing concentration of epoxide groups on the grafted
      P(GMA) brushes. In vitro cell adhesion and proliferation studies demonstrate that
      cell affinity and growth are significantly improved by the immobilization of
      gelatin on PCL film surfaces, and that this improvement is positively correlated
      to the amount of covalently immobilized gelatin. With the versatility of the ATRP
      process and tunable grafting efficacy of gelatin, this study offers a suitable
      methodology for the functionalization of biodegradable polyesters scaffolds to
      improve cell-material interactions.

PMID- 22589074
TI  - Evaluation of protein adsorption on atmospheric plasma deposited coatings
      exhibiting superhydrophilic to superhydrophobic properties.
AB  - Protein adsorption is one of the key parameters influencing the biocompatibility
      of medical device materials. This study investigates serum protein adsorption and
      bacterial attachment on polymer coatings deposited using an atmospheric pressure
      plasma jet system. The adsorption of bovine serum albumin and bovine fibrinogen
      (Fg) onto siloxane and fluorinated siloxane elastomeric coatings that exhibit
      water contact angles (theta) ranging from superhydrophilic (theta < 5 degrees )
      to superhydrophobic (theta > 150 degrees ) were investigated. Protein
      interactions were evaluated in situ under dynamic flow conditions by
      spectroscopic ellipsometry. Superhydrophilic coatings showed lower levels of
      protein adsorption when compared with hydrophobic siloxane coatings, where
      preferential adsorption was shown to occur. Reduced levels of protein adsorption
      were also observed on fluorinated siloxane copolymer coatings exhibiting
      hydrophobic wetting behaviour. The lower levels of protein adsorption observed on
      these surfaces indicated that the presence of fluorocarbon groups have the effect
      of reducing surface affinity for protein attachment. Analysis of superhydrophobic
      siloxane and fluorosiloxane surfaces showed minimal indication of protein
      adsorption. This was confirmed by bacterial attachment studies using a
      Staphylococcus aureus strain known to bind specifically to Fg, which showed
      almost no attachment to the superhydrophobic coating after protein adsorption
      experiments. These results showed the superhydrophobic surfaces to exhibit
      antimicrobial properties and significantly reduce protein adsorption.

PMID- 22589075
TI  - ARGET-ATRP synthesis and characterization of PNIPAAm brushes for quantitative
      cell detachment studies.
AB  - Stimuli responsive (or "smart") polymer brushes represent a non-toxic approach
      for achieving release of biofouling layers. Thermo-responsive poly(N
      isopropylacrylamide) (PNIPAAm) polymer brushes have been shown to modulate
      bacterial adhesion and release through transition between temperatures above and
      below the lower critical solution temperature (LCST ~32  degrees C) of PNIPAAm in
      water. In this article, we describe a convenient method to synthesize grafted
      PNIPAAm brushes over large areas for biological studies using a relatively simple
      and rapid method which allows atom transfer radical polymerization (ATRP) in
      presence of air using the activator regenerated electron transfer (ARGET)
      mechanism. PNIPAAm brushes were characterized using X-ray photoelectron
      spectroscopy, time-of-flight secondary ion mass spectroscopy, Fourier transform
      infrared spectroscopy, ellipsometry, and contact angle measurements. Our studies
      demonstrate that uniform, high purity PNIPAAm brushes with controlled and high
      molecular weight can be easily produced over large areas using ARGET-ATRP. We
      also report the use of a spinning disk apparatus to systematically and
      quantitatively study the detachment profiles of bacteria from PNIPAAm surfaces
      under a range (0-400 dyne/cm(2)) of shear stresses.

PMID- 22589076
TI  - Settlement behavior of zoospores of Ulva linza during surface selection studied
      by digital holographic microscopy.
AB  - Settlement of the planktonic dispersal stages of marine organisms is the crucial
      step for the development of marine biofouling. Four-dimensional holographic
      tracking reveals the mechanism by which algal spores select surfaces suitable for
      colonization. Quantitative analysis of the three dimensional swimming
      trajectories of motile spores of a macroalga (Ulva linza) in the vicinity of
      surfaces functionalized with different chemistries reveals that their search
      strategy and swimming behavior is correlated to the number of settled spores
      found in spore settlement bioassays conducted over 45 min. The spore motility and
      exploration behavior can be classified into different motion patterns, with their
      relative occurrence changing with the surface chemistry. Based on the detailed
      motility analysis we derived a model for the surface selection and settlement
      process of Ulva zoospores.

PMID- 22589077
TI  - Contactless laser-assisted patterning of surfaces for bio-adhesive microarrays.
AB  - Micropatterned surfaces with cell adhesive areas, delimited by protein repellent
      microstructures, are in high demand for its potential use as relevant biological
      assays. This is not only because such surfaces allow directing cell growth in a
      spatially localized and restricted manner, but also because they can be used to
      elucidate basic cell growth and orientation mechanisms. Here, it is presented a
      laser-assisted micropatterning technique to fabricate large area microstructures
      of poly (ethylene glycol) hydrogel onto a cell adhesive surface: a biofunctional
      maleic anhydride copolymer. By varying photoinitiator, laser intensity, copolymer
      as well as the hydrogel layer thickness, the optimum conditions to produce high
      quality features were found. The suitability of these micropatterned substrates
      for bioassay applications was proved by cell adhesion studies. The introduced
      procedure could be used to prepare a broad range of microarrays for certain
      bioanalytical approaches and to create different types of biofunctional surfaces.

PMID- 22589078
TI  - Epidemiology of pancreatic cancer and the role of family history.
AB  - Pancreatic cancer is a lethal disease for which only a small number of risk
      factors have been identified. In addition to older age, male gender, and black
      race, risk factors include smoking, obesity, long-standing diabetes and
      pancreatitis, and heavy alcohol use; allergies such as hay fever are related to
      lowered risk. Several genetic syndromes increase risk of pancreatic cancer. Work
      on more common genetic variants promises to reveal more potentially important
      genetic associations.

PMID- 22589079
TI  - Strong and selective binding of amiloride to an abasic site in RNA duplexes:
      thermodynamic characterization and microRNA detection.
AB  - Firmly tied: The binding affinity of amiloride for an abasic (AP) site-containing
      RNA duplex is two orders of magnitude superior to the affinity of the
      corresponding AP site-containing DNA duplex. The observed high binding affinity
      for the RNA duplex arises from a favorable enthalpy gain. The binding-induced
      fluorescence response of amiloride is applicable to microRNA detection.

PMID- 22589080
TI  - Preventing delirium in an acute hospital using a non-pharmacological
      intervention.
AB  - BACKGROUND: delirium is a clinical syndrome associated with multiple short and
      long-term complications and therefore prevention is an essential part of its
      management. This study was designed to assess the efficacy of multicomponent
      intervention in delirium prevention. METHODS: a total of 287 hospitalised
      patients at intermediate or high risk of developing delirium were randomised to
      receive a non-pharmacological intervention delivered by family members (144
      patients) or standard management (143 patients). The primary efficacy outcome was
      the occurrence of delirium at any time during the course of hospitalisation.
      Three validated observers performed the event adjudication by using the confusion
      assessment method screening instrument. RESULTS: there were no significant
      differences in the baseline characteristics between the two groups. The primary
      outcome occurred in 5.6% of the patients in the intervention group and in 13.3%
      of the patients in the control group (relative risk: 0.41; confidence interval:
      0.19-0.92; P = 0.027). CONCLUSION: the results of this study show that there is a
      benefit in the non-pharmacological prevention of delirium using family members,
      when compared with standard management of patients at risk of developing this
      condition.

PMID- 22589081
TI  - Lewis histo-blood group alpha1,3/alpha1,4 fucose residues may both mediate
      binding to GII.4 noroviruses.
AB  - Human noroviruses cause recurrent epidemics of gastroenteritis known to be
      dominated by the clinically important GII.4 genotype which recognizes human
      Secretor gene-dependent ABH histo-blood group antigens (HBGAs) as attachment
      factors. There is increasing evidence that GII.4 noroviruses have undergone
      evolutionary changes to recognize Lewis antigens and non-Secretor saliva. In this
      study, we have investigated the possibilities of the Lewis alpha1,3/alpha1,4
      fucoses as mediators of binding of GII.4 noroviruses to Lewis antigens. The study
      was carried out using molecular dynamics simulations of Lewis type-1 and type-2
      chain HBGAs in complex with VA387 P domain dimers in explicit water. Based on the
      computer simulations, we suggest the possibility of two receptor binding modes
      for Lewis HBGAs: the "Secretor pose" with the Secretor Fucalpha1,2 in the binding
      site and the "Lewis pose" with the Lewis Fucalpha1,3/alpha1,4 residues in the
      binding site. This was further supported by an extensive GlyVicinity analysis of
      the Protein Data Bank with respect to the occurrence of the Lewis and Secretor
      poses in complexes of Lewis antigens with lectins and antibodies as well as GII
      norovirus strains. The Lewis pose can also explain the interactions of GII.4
      norovirus strains with Le(x) and SLe(x) structures. Moreover, the present model
      suggests binding of complex branched polysaccharides, with the Lewis antigens at
      the nonreducing end, to P domain dimers of GII.4 strains. Our results are
      relevant for understanding the evolution of norovirus binding specificities and
      for in silico design of future antiviral therapeutics.

PMID- 22589082
TI  - Effects of age on genetic influence on bone loss over 17 years in women: the
      Healthy Ageing Twin Study (HATS).
AB  - The rate of bone loss varies across the aging period via multiple complex
      mechanisms. Therefore, the role of genetic factors on bone loss may also change
      similarly. In this study, we investigated the effect of age on the genetic
      component of bone loss in a large twin-based longitudinal study. During 17 years
      of follow-up in TwinsUK and Healthy Ageing Twin Study (HATS), 15,491 hip and
      lumbar spine dual-energy X-ray absorptiometry (DXA) scans were performed in 7056
      twins. Out of these subjects, 2716 female twins aged >35 years with at least two
      scans separated for >4 years (mean follow-up 9.7 years) were included in this
      analysis. We used a mixed-effects random-coefficients regression model to predict
      hip and spine bone mineral density (BMD) values for exact ages of 40, 45, 50, 55,
      60, 65, 70, 75, and 80 years, with adjustment for baseline age, weight, height,
      and duration of hormone replacement therapy. We then estimated heritability of
      the changes in BMD measures between these age ranges. Heritability estimates for
      cross-sectional hip and spine BMD were high (ranging between 69% and 88%) at
      different ages. Heritability of change of BMD was lower and more variable,
      generally ranging from 0% to 40% for hip and 0% to 70% for spine; between age 40
      and 45 years genetic factors explained 39.9% (95% confidence interval [CI], 25%
      53%) of variance of BMD loss for total hip, 46.4% (95% CI, 32%-58%) for femoral
      neck, and 69.5% (95% CI, 59%-77%) for lumbar spine. These estimates decreased
      with increasing age, and there appeared to be no heritability of BMD changes
      after the age of 65 years. There was some evidence at the spine for shared
      genetic effects between cross-sectional and longitudinal BMD. Whereas genetic
      factors appear to have an important role in bone loss in early postmenopausal
      women, nongenetic mechanisms become more important determinants of bone loss with
      advanced age.

PMID- 22589084
TI  - Tailoring the spectral response of liquid waveguide diagnostic platforms.
AB  - Liquid filled waveguides that form the basis for on-chip biophotonics diagnostic
      platforms have primarily found application in fluorescence and Raman spectroscopy
      experiments that require sensitive discrimination between weak analyte signals
      and a variety of background signals. Primary sources of background signal can
      include light from excitation sources (strong, narrow frequency band) and
      photoluminescence generated in waveguide cladding layers (weak, wide frequency
      band). Here we review both solid and liquid core filtering structures which are
      based on anti-resonant reflection that can be integrated with waveguides for
      attenuating undesirable optical bands. Important criteria to consider for an
      optimized biosensor include cladding layer materials that minimize broad-spectrum
      photoluminescence and optimize layer thicknesses for creating a desired spectral
      response in both solid and liquid guiding layers, and a microfabrication process
      capable of producing regions with variable spectral response. New results
      describing how spurious fluorescence can be minimized by optimized thermal growth
      conditions and how liquid-core filter discrimination can be tuned with liquid
      core waveguide length are presented.

PMID- 22589085
TI  - Ligand conformation dictates membrane and endosomal trafficking of arginine
      glycine-aspartate (RGD)-functionalized mesoporous silica nanoparticles.
AB  - Recent breakthrough research on mesoporous silica nanoparticle (MSN) materials
      has illustrated their significant potential in biological applications due to
      their excellent drug delivery and endocytotic behavior. We set out to determine
      if MSN, covalently functionalized with conformation specific bioactive molecules
      (either linear or cyclic RGD ligands), behave towards mammalian cells in a
      similar manner as the free ligands. We discovered that RGD immobilized on the MSN
      surface did not influence the integrity of the porous matrix and improved the
      endocytosis efficiency of the MSN materials. Through competition experiments with
      free RGD ligands, we also discovered a conformation specific receptor-integrin
      association. The interaction between RGD immobilized on the MSN surface and
      integrins plays an important role in endosome trafficking, specifically dictating
      the kinetics of endosomal escape. Thus, covalent functionalization of
      biomolecules on MSN assists in the design of a system for controlling the
      interface with cancer cells.

PMID- 22589086
TI  - Systems biology: molecular networks and disease.

PMID- 22589083
TI  - Acute heat stress prior to downhill running may enhance skeletal muscle
      remodeling.
AB  - Heat shock proteins (HSPs) are chaperones that are known to have important roles
      in facilitating protein synthesis, protein assembly and cellular protection.
      While HSPs are known to be induced by damaging exercise, little is known about
      how HSPs actually mediate skeletal muscle adaption to exercise. The purpose of
      this study was to determine the effects of a heat shock pretreatment and the
      ensuing increase in HSP expression on early remodeling and signaling (2 and 48 h)
      events of the soleus (Sol) muscle following a bout of downhill running. Male
      Wistar rats (10 weeks old) were randomly assigned to control, eccentric exercise
      (EE; downhill running) or heat shock + eccentric exercise (HS; 41 degrees C for
      20 min, 48 h prior to exercise) groups. Markers of muscle damage, muscle
      regeneration and intracellular signaling were assessed. The phosphorylation (p)
      of HSP25, Akt, p70s6k, ERK1/2 and JNK proteins was also performed. As expected,
      following exercise the EE group had increased creatine kinase (CK; 2 h) and
      mononuclear cell infiltration (48 h) compared to controls. The EE group had an
      increase in p-HSP25, but there was no change in HSP72 expression, total protein
      concentration, or neonatal MHC content. Additionally, the EE group had increased
      p-p70s6k, p-ERK1/2, and p-JNK (2 h) compared to controls; however no changes in p
      Akt were seen. In contrast, the HS group had reduced CK (2 h) and mononuclear
      cell infiltration (48 h) compared to EE. Moreover, the HS group had increased
      HSP72 content (2 and 48 h), total protein concentration (48 h), neonatal MHC
      content (2 and 48 h), p-HSP25 and p-p70s6k (2 h). Lastly, the HS group had
      reduced p-Akt (48 h) and p-ERK1/2 (2 h). These data suggest that heat shock
      pretreatment and/or the ensuing HSP72 response may protect against muscle damage,
      and enhance increases in total protein and neonatal MHC content following
      exercise. These changes appear to be independent of Akt and MAPK signaling
      pathways.

PMID- 22589087
TI  - DNA methylation profiling distinguishes three clusters of breast cancer cell
      lines.
AB  - Methylation change plays an important role in many cellular systems, including
      cancer development. During recent years, genome-wide or large-scale methylation
      data has become available thanks to rapid advances in high-throughput
      biotechnologies. So far, researchers have always used gene expression profiling
      to study disease subtypes and related therapies. In this study, we investigated
      methylation profiles in 30 breast cancer cell lines using methylation data
      generated by microarray technologies. Strong variation of the number of
      methylation peaks was found among these 30 cell lines; however, more peaks were
      found in the upstream regions than in downstream regions of genes. We further
      grouped the methylation profiles of these cell lines into three consensus
      clusters. Finally, we performed an integrative analysis of breast cancer cell
      lines using both methylation and gene-expression profiling data. There was no
      significant correlation between methylation-profiling subtypes and gene
      expression profiling subtypes, suggesting the complex nature of methylation in
      the regulation of gene expression. However, we found basal B cell lines appeared
      exclusively in two methylation clusters. Although these results are preliminary,
      this study suggests that methylation profiling might be promising in disease
      subtype classification and the development of therapeutic strategies.

PMID- 22589088
TI  - microRNA dysregulation in prostate cancer: network analysis reveals preferential
      regulation of highly connected nodes.
AB  - microRNAs (miRNAs) are small RNAs shown to contribute to a number of cellular
      processes including cell growth, differentiation, and apoptosis. MiRNAs regulate
      gene expression of their targets post-transcriptionally by binding to messenger
      RNA (mRNA), causing translational inhibition or mRNA degradation. Dysregulation
      of miRNA expression can promote cancer formation and progression. Research has
      largely focused on the function and expression of single miRNAs. However, complex
      physiological processes require the interaction, regulation and coordination of
      many molecules including miRNAs and proteins. Highly connected molecules often
      serve important roles in the cell. A protein-protein interaction network of
      established miRNA targets confirmed these proteins to be highly connected and
      essential to the cell, affecting tumorigenesis, cell growth/proliferation,
      cellular death, cell assembly, and maintenance pathways. This analysis showed
      that miRNAs contribute to the overall health of the prostate, and their aberrant
      expression destabilized homeostatic balance. This integrative network approach
      can reveal important miRNAs and proteins in prostate cancer that will be useful
      to identify specific disease biomarkers, which may be used as targets for
      therapeutics or drugs in themselves.

PMID- 22589089
TI  - Massive human co-expression network and its medical applications.
AB  - Network-based analysis is indispensable in analyzing high-throughput biological
      data. Based on the assumption that the variation of gene interactions under given
      biological conditions could be better interpreted in the context of a large-scale
      and wide variety of developmental, tissue, and disease conditions, we leverage
      the large quantity of publicly available transcriptomic data >40,000 HG U133A
      Affymetrix microarray chips stored in ArrayExpress
      (http://www.ebi.ac.uk/arrayexpress/) using MetaOmGraph
      (http://metnet.vrac.iastate.edu/MetNet_MetaOmGraph.htm). From this data, 18,637
      chips encompassing over 500 experiments containing high-quality data (18637 Hu
      dataset) were used to create a globally stable gene co-expression network (18637
      Hu-co-expression-network). Regulons, groups of highly and consistently co
      expressed genes, were obtained by partitioning the 18637 Hu-co-expression-network
      using an Markov clustering algorithm (MCL). The regulons were demonstrated to be
      statistically significant using a gene ontology (GO) term overrepresentation test
      combined with evaluation of the effects of gene permutations. The regulons
      include ca. 12% of human genes, interconnected by 31,471 correlations. All
      network data and metadata are publically available
      (http://metnet.vrac.iastate.edu/MetNet_MetaOmGraph.htm). Text mining of these
      metadata, GO term overrepresentation analysis, and statistical analysis of
      transcriptomic experiments across multiple environmental, tissue, and disease
      conditions, has revealed novel fingerprints distinguishing central nervous system
      (CNS)-related conditions. This study demonstrates the value of mega-scale network
      based analysis for biologists to further refine transcriptomic data, derived from
      a particular condition, to study the global relationships between genes and
      diseases, and to develop hypotheses that can inform future research.

PMID- 22589090
TI  - Newborn umbilical cord blood DNA methylation and gene expression levels exhibit
      limited association with birth weight.
AB  - Most cases of fetal growth retardation are unexplained. These newborns are at
      high risk of serious illness or death in the neonatal period and exhibit
      significantly increased risk of specific chronic illnesses later in life. While
      there are several hypotheses to explain the well-established association between
      low birth weight and later risk of disease, the true etiology is unknown. To
      search for molecular patterns that may explain the biological basis for reduced
      fetal growth in a clinically normal cohort, and possibly provide clues for the
      lifelong increased risk of disease, we surveyed genome-wide DNA methylation and
      gene expression patterns in the umbilical cord blood of newborns born in Shelby
      County, TN. While we did not find genome-wide significant associations of birth
      weight with either leukocytic gene expression or DNA methylation, we did find
      suggestive associations in several genes with known effects on pre- or postnatal
      growth and health. As with previous molecular epidemiological studies of birth
      weight, we did not sample the most biologically relevant tissues in the newborn.
      However, our discovery of biologically plausible associations in a peripheral
      tissue suggests that further studies of tissues key to fetal growth regulation
      are warranted.

PMID- 22589091
TI  - Network-assisted investigation of antipsychotic drugs and their targets.
AB  - Antipsychotic drugs are tranquilizing psychiatric medications primarily used in
      the treatment of schizophrenia and similar severe mental disorders. So far, most
      of these drugs have been discovered without knowing much on the molecular
      mechanisms of their actions. The available large amount of pharmacogenetics,
      pharmacometabolomics, and pharmacoproteomics data for many drugs makes it
      possible to systematically explore the molecular mechanisms underlying drug
      actions. In this study, we applied a unique network-based approach to investigate
      antipsychotic drugs and their targets. We first retrieved 43 antipsychotic drugs,
      42 unique target genes, and 46 adverse drug interactions from the DrugBank
      database and then generated a drug-gene network and a drug-drug interaction
      network. Through drug-gene network analysis, we found that seven atypical
      antipsychotic drugs tended to form two clusters that could be defined by drugs
      with different target receptor profiles. In the drug-drug interaction network, we
      found that three drugs (zuclopenthixol, ziprasidone, and thiothixene) tended to
      have more adverse drug interactions than others, while clozapine had fewer
      adverse drug interactions. This investigation indicated that these antipsychotics
      might have different molecular mechanisms underlying the drug actions. This pilot
      network-assisted investigation of antipsychotics demonstrates that network-based
      analysis is useful for uncovering the molecular actions of antipsychotics.

PMID- 22589092
TI  - Identification of metabolic changes in genetically unstable stem cells by using
      model analysis of gene expression.
AB  - Stem-cell research seeks to address many different questions related to
      fundamental stem-cell function with the ultimate goal of being able to control
      and utilize stem cells for a broad range of therapeutic needs. While a large
      amount of work is focused on discovering and controlling differentiation
      mechanisms in stem cells, an equally interesting and important area of work is to
      understand the basics of stem-cell propagation and self-renewal. With high
      throughput genomics and transcriptomic information on hand, it is becoming
      possible to address some of the detailed mechanistic processes occurring in stem
      cells, though interpretation of these data is often difficult. In this work, stem
      cells with genetic abnormalities were compared to genetically normal stem cells
      using gene-expression array data integrated with a large-scale metabolic model to
      help interpret changes in metabolism resulting in the identification of several
      metabolic pathways that were different in the normal and abnormal cells.

PMID- 22589093
TI  - A core process in receptor function, general anesthesia, sleep, and aging.
AB  - The diffusion of ligands and proteins was proposed to be guided by chreodes in
      water organized by protein-surface side chains with varying hydropathic states.
      These chreodes are proposed to be the target of volatile general anesthetic
      agents. The similarity between this effect and sleep deprivation leads to a
      proposal of an external agent responsible for sleep. This agent is elemental
      nitrogen. An extension of this effect is the concept that elemental nitrogen is a
      core factor in aging.

PMID- 22589094
TI  - Integration of diverse statistical evidence of gene-trait association in systems
      biology studies.
AB  - The rapid advancement of high-throughput genomic assay technologies has generated
      large amounts of diverse genomic data in disparate human populations and
      diseases. These data provide a unique opportunity for biomedical investigators to
      systematically study multifaceted aspects of genes' involvement in the biological
      processes underlying important traits from the systems biology perspective. An
      important component in such a study is the inference that integrates diverse
      lines of statistical evidence for gene-trait association from the observed trait
      values and the massive numbers of measured genomic features. A novel integrated
      statistical analysis procedure is developed in this paper and is illustrated by
      an application in studying childhood leukemia.

PMID- 22589095
TI  - Nested hierarchal organization of conservation for microRNAs and their putative
      targets to Drosophila melanogaster.
AB  - This study examined microRNA network properties traced through taxonomic
      hierarchy considering both the acquisition of potential network targets and
      regulators. Primary literature review and database analyses were conducted to
      establish modules of conserved microRNAs across metazoan taxonomy. A hierarchical
      schema for the conservation of microRNAs and their putative targets to Drosophila
      melanogaster was engineered through comprehensive meta-analysis, and conservation
      history of 90.39% of the total Drosophila dataset could be resolved through this
      hierarchical sampling regime; tracing from taxonomic order down to empire. The
      findings presented in this study represent a documentation of Drosophila microRNA
      regulatory network behavior thorough taxonomic hierarchy. MicroRNA regulatory
      network properties were found to transect taxonomic hierarchy. Newly acquired
      microRNAs from novel families reinforce the pre-existing regulatory network,
      while expanding the target list to include a small number of novel genes. Lineage
      specific microRNAs were found to exhibit far fewer conserved targets than do the
      more broadly conserved microRNAs; even when considering only more recently
      emerged targets. There was a dramatic expansion in network complexity with the
      expansion of the microRNA repertoire, and this corresponds to the expansion in
      biological complexity.

PMID- 22589096
TI  - A new era of the vaginal microbiome: advances using next-generation sequencing.
AB  - Until recently, bacterial species that inhabit the human vagina have been
      primarily studied using organism-centric approaches. Understanding how these
      bacterial species interact with each other and the host vaginal epithelium is
      essential for a more complete understanding of vaginal health. Molecular
      approaches have already led to the identification of uncultivated bacterial taxa
      associated with bacterial vaginosis. Here, we review recent studies of the
      vaginal microbiome and discuss how culture-independent approaches, such as
      applications of next-generation sequencing, are advancing the field and shifting
      our understanding of how vaginal health is defined. This work may lead to
      improved diagnostic tools and treatments for women who suffer from, or are at
      risk for, vaginal imbalances, pregnancy complications, and sexually acquired
      infections. These approaches may also transform our understanding of how host
      genetic factors, physiological conditions (e.g., menopause), and environmental
      exposures (e.g., smoking, antibiotic usage) influence the vaginal microbiome.

PMID- 22589097
TI  - Predicting antigenicity of proteins in a bacterial proteome; a protein microarray
      and naive Bayes classification approach.
AB  - Discovery of novel antigens associated with infectious diseases is fundamental to
      the development of serodiagnostic tests and protein subunit vaccines against
      existing and emerging pathogens. Efforts to predict antigenicity have relied on a
      few computational algorithms predicting signal peptide sequences (SignalP),
      transmembrane domains, or subcellular localization (pSort). An empirical protein
      microarray approach was developed to scan the entire proteome of any infectious
      microorganism and empirically determine immunoglobulin reactivity against all the
      antigens from a microorganism in infected individuals. The current database from
      this activity contains quantitative antibody reactivity data against 35,000
      proteins derived from 25 infectious microorganisms and more than 30 million data
      points derived from 15,000 patient sera. Interrogation of these data sets has
      revealed ten proteomic features that are associated with antigenicity, allowing
      an in silico protein sequence and functional annotation based approach to triage
      the least likely antigenic proteins from those that are more likely to be
      antigenic. The first iteration of this approach applied to Brucella melitensis
      predicted 37% of the bacterial proteome containing 91% of the antigens
      empirically identified by probing proteome microarrays. In this study, we
      describe a naive Bayes classification approach that can be used to assign a
      relative score to the likelihood that an antigen will be immunoreactive and
      serodiagnostic in a bacterial proteome. This algorithm predicted 20% of the B.
      melitensis proteome including 91% of the serodiagnostic antigens, a nearly
      twofold improvement in specificity of the predictor. These results give us
      confidence that further development of this approach will lead to further
      improvements in the sensitivity and specificity of this in silico predictive
      algorithm.

PMID- 22589098
TI  - Prediction and comparison of Salmonella-human and Salmonella-Arabidopsis
      interactomes.
AB  - Salmonellosis caused by Salmonella bacteria is a food-borne disease and a
      worldwide health threat causing millions of infections and thousands of deaths
      every year. This pathogen infects an unusually broad range of host organisms
      including human and plants. A better understanding of the mechanisms of
      communication between Salmonella and its hosts requires identifying the
      interactions between Salmonella and host proteins. Protein-protein interactions
      (PPIs) are the fundamental building blocks of communication. Here, we utilize the
      prediction platform BIANA to obtain the putative Salmonella-human and Salmonella
      Arabidopsis interactomes based on sequence and domain similarity to known PPIs. A
      gold standard list of Salmonella-host PPIs served to validate the quality of the
      human model. 24,726 and 10,926 PPIs comprising interactions between 38 and 33
      Salmonella effectors and virulence factors with 9,740 human and 4,676 Arabidopsis
      proteins, respectively, were predicted. Putative hub proteins could be
      identified, and parallels between the two interactomes were discovered. This
      approach can provide insight into possible biological functions of so far
      uncharacterized proteins. The predicted interactions are available via a web
      interface which allows filtering of the database according to parameters provided
      by the user to narrow down the list of suspected interactions. The interactions
      are available via a web interface at http://sbi.imim.es/web/SHIPREC.php.

PMID- 22589099
TI  - Using electrophoretic exclusion to manipulate small molecules and particles on a
      microdevice.
AB  - Electrophoretic exclusion, a novel separations technique that differentiates
      species in bulk solution using the opposing forces of electrophoretic velocity
      and hydrodynamic flow, has been adapted to a microscale device. Proof-of
      principle experiments indicate that the device was able to exclude small
      particles (1 MUm polystyrene microspheres) and fluorescent dye molecules
      (rhodamine 123) from the entrance of a channel. Additionally, differentiation of
      the rhodamine 123 and polystyrene spheres was demonstrated. The current studies
      focus on the direct observation of the electrophoretic exclusion behavior on a
      microchip.

PMID- 22589100
TI  - Microchip electrophoresis of DNA following preconcentration at photopatterned gel
      membranes.
AB  - Rapid separation of nucleic acids by microchip electrophoresis could streamline
      many biological applications, but conventional chip injection strategies offer
      limited sample stacking, and thus limited sensitivity of detection. We
      demonstrate the use of photopatterned polyacrylamide membranes in a glass
      microfluidic device, with or without fixed negative charges, for preconcentration
      of double-stranded DNA prior to electrophoretic separation to enhance detection
      limits. We compared performance of the two membrane formulations (neutral or
      negatively charged) as a function of DNA fragment size, preconcentration time,
      and preconcentration field strength, with the intent of optimizing
      preconcentration performance without degrading the subsequent electrophoretic
      separation. Little size-dependent bias was observed for either membrane
      formulation when concentrating dsDNA > 100 bp in length, while the negatively
      charged membrane more effectively blocks passage of single-stranded
      oligonucleotide DNA (20-mer ssDNA). Baseline resolution of a six-band dye-labeled
      ladder with fragments 100-2000 bp in size was obtained in <120 s of separation
      time, with peak efficiencies in the range of 2000-15,000 plates/cm, and detection
      limits as low as 1 pM per single dye-labeled fragment. The degree of
      preconcentration is tunable by at least 49-fold, although the efficiency of
      preconcentration was found to have diminishing returns at high field and/or long
      times. The neutral membrane was found to be more robust than the negatively
      charged membrane, with approximately 2.5-fold larger peak area during the
      subsequent separation, and less decrease in resolution upon increasing the
      preconcentration field strength.

PMID- 22589101
TI  - Determination of heavy metal ions by microchip capillary electrophoresis coupled
      with contactless conductivity detection.
AB  - An integrated detection circuitry based on a lock-in amplifier was designed for
      contactless conductivity determination of heavy metals. Combined with a simple
      structure electrophoresis microchip, the detection system is successfully
      utilized for the separation and determination of various heavy metals. The
      influences of the running buffer and detection conditions on the response of the
      detector have been investigated. Six millimole 2-morpholinoethanesulfonic acid +
      histidine were selected as buffer for its stable baseline and high sensitivity.
      The best signals were recorded with a frequency of 38 kHz and 20 V(pp). The
      results showed that Mn(2+), Cd(2+), Co(2+), and Cu(2+) can be successfully
      separated and detected within 100 s by our system. The detection limits for five
      heavy metals (Mn(2+), Pb(2+), Cd(2+), Co(2+), and Cu(2+)) were determined to
      range from about 0.7 to 5.4 MUM. This microchip system performs a crucial step
      toward the realization of a simple, inexpensive, and portable analytical device
      for metal analysis.

PMID- 22589102
TI  - Enhanced detection of gold nanoparticles in agarose gel electrophoresis.
AB  - Gel electrophoresis is a powerful tool in gold nanoparticle (AuNP) research.
      While the technique is sensitive to the size, charge, and shape of particles, its
      optimal performance requires a relatively large amount of AuNP in the loading
      wells for visible detection of bands. We here describe a novel and more sensitive
      method for detecting AuNPs in agarose gels that involves staining the gel with
      the common organic fluorophore fluorescein, to produce AuNP band intensities that
      are linear with nanoparticle concentration and almost an order of magnitude
      larger than those obtained without staining the gel.

PMID- 22589103
TI  - Competitive CE-UV binding tests for selective recognition of bisphenol A by
      molecularly imprinted polymer particles.
AB  - Capillary electrophoresis with ultraviolet detection (CE-UV) was used to perform
      competitive binding tests to demonstrate the selective recognition of bisphenol A
      (BPA) by molecularly imprinted polymer (MIP) particles. Cross-linking
      polymerization of methacrylic acid (MAA) and ethylene glycol dimethacrylate
      (EGDMA) in the presence of BPA yielded MIP particles with an average diameter of
      164 +/- 15 nm. Their ability to recognize BPA in the presence of nonionic,
      anionic, and cationic water contaminants was investigated. Binding efficiency was
      rapidly determined, after sequential injection of particles first and compounds
      next into the fused-silica capillary provided a short overlapping time during
      their electrophoretic migrations. The MIP particles exhibited high-binding
      efficiency (99 +/- 1%) for BPA. Neither diclofenac nor metformin affected BPA
      binding, and 2-hydroxy-4-methoxybenzophenone was even displaced from the
      particles by BPA. These results verified the high selectivity of MIP toward its
      target compound.

PMID- 22589105
TI  - Nanotube-grafted polyacrylamide hydrogels for electrophoretic protein separation.
AB  - Multiwalled carbon nanotube-modified polyacrylamide gels have been employed for
      the electrophoretic separation of proteins. Two approaches are compared in this
      investigation, one using nanotubes only as fillers inside the gel matrix and the
      other using nanotubes as catalyst for polymerization of acrylamide. In both the
      cases, polymerization of acryl-amide/bisacrylamide has been carried out in situ
      in the presence of nanotubes dispersed in the gel buffer containing monomer and
      cross-linker. In the former case, initiator and catalyst have been added after
      ultrasonication of nanotubes in the gel buffer mixture where the nanotubes play
      the role of filler. On the other hand, the second approach precludes use of
      catalyst and involves addition of initiator alone during ultrasonication of
      nanotubes in the gel buffer containing monomer and cross-linker, which leads to
      the formation of nanotube-grafted gel after 25 min. When nanotubes are used as a
      catalyst instead of N,N,N',N'-tetramethylethylenediamine, pore size distribution
      of the gel matrix and linearity of molecular weight calibration plots are found
      to be improved. In addition, other issues associated with the use of an external
      catalyst like handling the moisture-sensitive and corrosive reagent and
      associated irreproducibility are addressed in this approach.

PMID- 22589104
TI  - Optimization of large gel 2D electrophoresis for proteomic studies of skeletal
      muscle.
AB  - We describe improved methods for large format, two-dimensional gel
      electrophoresis (2DE) that improve protein solubility and recovery, minimize
      proteolysis, and reduce the loss of resolution due to contaminants and
      manipulations of the gels, and thus enhance quantitative analysis of protein
      spots. Key modifications are: (i) the use of 7 M urea and 2 M thiourea, instead
      of 9 M urea, in sample preparation and in the tops of the gel tubes; (ii)
      standardized deionization of all solutions containing urea with a mixed bed ion
      exchange resin and removal of urea from the electrode solutions; and (iii) use of
      a new gel tank and cooling device that eliminate the need to run two separating
      gels in the SDS dimension. These changes make 2DE analysis more reproducible and
      sensitive, with minimal artifacts. Application of this method to the soluble
      fraction of muscle tissues reliably resolves ~1800 protein spots in adult human
      skeletal muscle and over 2800 spots in myotubes.

PMID- 22589106
TI  - Coupling of native IEF and extended X-ray absorption fine structure to
      characterize zinc-binding sites from pI isoforms of SOD1 and A4V pathogenic
      mutant.
AB  - Extended X-ray absorption fine structure (EXAFS) has already provided high
      resolution structures of metal-binding sites in a wide variety of
      metalloproteins. Usually, EXAFS is performed on purified metalloproteins either
      in solution or crystallized form but purification steps are prone to modify the
      metallation state of the protein. We developed a protocol to couple EXAFS
      analysis to metalloprotein separation using native gel electrophoresis. This
      coupling opens a large field of applications as metalloproteins can be
      characterized in their native state avoiding purification steps. Using native
      isoelectric focusing, the method enables the EXAFS analysis of metalloprotein pI
      isoforms. We applied this methodology to SOD1, wild-type, and Ala4Val mutant
      (A4V), a mutation found in amyotrophic lateral sclerosis (ALS) because decreased
      Zn affinity to SOD1 mutants is suggested to be involved in the pathogenesis of
      this neurodegenerative disease. We observed similar coordination structures for
      Zn in wild-type and mutant proteins, in all measured pI isoforms, demonstrating
      the feasibility of EXAFS on electrophoresis gels and suggesting that the Zn
      binding site is not structurally modified in A4V SOD1 mutant.

PMID- 22589107
TI  - Stoichiometry of the MexA-OprM binding, as investigated by blue native gel
      electrophoresis.
AB  - Multidrug resistance has become a serious concern in the treatment of bacterial
      infections. A prominent role is ascribed to the active efflux of xenobiotics out
      of the bacteria by a tripartite protein machinery. The mechanism of drug
      extrusion is rather well understood, thanks to the X-ray structures obtained for
      the Escherichia coli TolC/AcrA/AcrB model system and the related Pseudomonas
      aeruginosa OprM/MexA/MexB. However, many questions remain unresolved, in
      particular the stoichiometry of the efflux pump assembly. On the basis of blue
      native polyacrylamide gel electrophoresis (BN-PAGE) (Wittig et al., Nat. Protoc.
      2006, 1, 418-428), we analyzed the binding stoichiometry of both palmitylated and
      non-palmitylated MexA with the cognate partner OprM trimer at different ratios
      and detergent conditions. We found that beta-octyl glucopyranoside (beta-OG)
      detergent was not suitable for this technique. Then we proved that MexA has to be
      palmitylated in order to stabilized the complex formation with OprM. Finally, we
      provided evidence for a two by two (2, 4, 6, or upper) binding of palmitylated
      MexA per trimer of OprM.

PMID- 22589108
TI  - Staining-free gel electrophoresis-based multiplex enzyme assay using DNA and
      peptide dual-functionalized gold nanoparticles.
AB  - We report a simple staining-free gel electrophoresis method to simultaneously
      probe protease and nuclease. Utilizing gold nanoparticles (Au-NPs) dual
      functionalized with DNA and peptide, the presence and concentration of nuclease
      and protease are determined concurrently from the relative position and intensity
      of the bands in the staining-free gel electrophoresis. The use of Au-NPs
      eliminates the need for staining processes and enables naked eye detection, while
      a mononucleotide-mediated approach facilitates the synthesis of DNA/peptide
      conjugated Au-NPs and simplifies the operation procedures. Multiplex detection
      and quantification of DNase I and trypsin are successfully demonstrated.

PMID- 22589109
TI  - Native analysis of plasma-derived clotting factor VIII concentrates: "sponge
      effect" and contaminants.
AB  - In the present study, we analysed two commercially available plasma-derived FVIII
      preparations, Beriate and Emoclot, through native gel-based approaches (CN-PAGE).
      The rationale behind this study was to assess whether protein complexes from
      plasma resisted the aggressive manufacturing processes. A preliminary analysis of
      plasma complexes was performed focusing on the molecular weight range between 45
      kDa and 1 MDa. As a result, we could evidence in both preparations the presence
      of complexes, which resisted the cryoprecipitation, chromatographic and heat
      treatment processing steps. These complexes behaved in a "sponge-effect"-like
      fashion through the enrichment of otherwise less abundant contaminants. The use
      of an alternative electrophoretic approach such as CN-PAGE allowed us to confirm
      2DE-based observations and expand the list of non-FVIII proteins which
      contaminate the preparations.

PMID- 22589110
TI  - Development of multiplex PCR system with 15 X-STR loci and genetic analysis in
      three nationality populations from China.
AB  - The aim of this study is to develop a new multiplex PCR system that
      simultaneously amplifies the 15 X-chromosome short tandem repeats (X-STRs) loci
      in the same PCR reaction, and to obtain the 15 X-STR loci database in three
      nationality populations from China. This multiplex system includes DXS7133,
      DXS6801, DXS981, DXS6809, DXS7424, DXS6789, DXS9898, DXS7132, GATA165B12, DXS101,
      DXS10075, DXS6800, GATA31E08, DXS10074, and DXS10079, which were successfully
      analyzed on 1251 DNA samples (670 males and 581 females) from Guangdong Han
      population, Xinjiang Uigur and Kazakh. The allele frequencies and mutation rates
      of the 15 loci were investigated, and the allele frequency distribution among
      different populations was compared. A total of 6-17 alleles for each locus were
      observed and altogether 170 alleles for all the selected loci were found.
      Thirteen cases with mutation of the above loci were detected in 11,850 meioses.
      Pairwise comparisons of the allele frequencies distribution showed significant
      differences in most loci among different populations. The results indicate that
      this multiplex system may provide high polymorphism information for kinship
      testing and relationship investigations, and it is necessary to gain allele
      frequency and mutation rate of different population for forensic application.

PMID- 22589111
TI  - Rapid testing of clopidogrel resistance by genotyping of CYP2C19 and CYP2C9
      polymorphisms using denaturing on-chip capillary electrophoresis.
AB  - Antiplatelet therapy is a cornerstone of cardiovascular treatment in patients
      with coronary artery disease and after myocardial infarction. Clopidogrel has
      become a popular antiplatelet agent due to its fast action and low frequency of
      adverse effects. Kinetics of clopidogrel metabolism is driven by enzymatic
      activity of the Cytochrome P450 system. Genotyping of CYP2C19 and CYP2C9
      polymorphisms allows to identify slow metabolizers showing resistance to
      clopidogrel therapy. Today, a number of PCR-based techniques for single
      nucleotide polymorphism genotyping directed at clopidogrel resistance
      polymorphisms are in use. Here, we describe a new alternative genotyping approach
      combining the separation power of denaturing capillary electrophoresis with the
      analysis speed and ease of use of Bioanalyzer chipCE platform. Using an upgraded
      heater control, we present an optimization for allele separation of CYP2C19
      I331V, CYP2C9 R144C, and CYP2C9 I359L polymorphisms employing run temperatures of
      up to 55 degrees C. We demonstrate rapid and accessible approach to reproducible
      clopidogrel resistance with feasibility and low cost.

PMID- 22589112
TI  - Dielectrophoresis: a model to transport drugs directly into teeth.
AB  - The article describes an innovative delivery system based on the principles of
      dielectrophoresis to transport drugs directly into site-specific intraoral
      targets. The hypothesis that a drug can be driven into tooth enamel during the
      application of an applied electrical potential difference was tested by the
      authors in in vitro studies comparing dielectrophoresis to diffusion to transport
      carbamide peroxide and fluoride. The studies showed that these agents can be
      transported directly into teeth using an alternating current (AC) electric field
      more effectively than diffusion. It was found that a 20-min bleaching treatment
      on human teeth with dielectrophoresis increased carbamide peroxide absorption by
      104% and, on average, improved the change in shade guide unit 14 times from 0.6
      SGU to 9 SGU. After applying a 1.23% acidulated phosphate fluoride gel to bovine
      incisors for 20 min by dielectrophoresis or diffusion, analysis with wavelength
      dispersive spectrometry determined that dielectrophoresis doubled fluoride uptake
      in the superficial layers compared to diffusion, and drove the fluoride
      significantly deeper into enamel with an uptake 600% higher than diffusion at 50
      MUm depth. Finally, dielectrophoresis promises to be a viable model that can
      potentially be used clinically to deliver other targeted drugs of variable
      molecular weight and structure.

PMID- 22589113
TI  - Atmospheric pressure ion lens extends the stable operational region of an
      electrospray ion source for capillary electrophoresis-mass spectrometry.
AB  - An atmospheric ion lens incorporated into an electrospray ion source for
      capillary electrophoresis-mass spectrometry (CE-MS) is found to extend the stable
      operational regions for both flow rates and electrospray ionization (ESI)
      voltages. The stable operating conditions for the ESI source with and without the
      ion lens were characterized. The results showed that the stable operation region
      was widest when the voltage difference between the sprayer and the ion lens
      ranges from 2.6 to 2.8 kV, and under these condition, the CE-MS interface can be
      adapted to a broader range of electroosmotic and modifier flow rates. Modeling of
      the electric field in the electrospray ion source with the ion lens suggests that
      the extension of the stable region is attributed to the flatter equipotential
      surfaces around the sprayer tip and higher electric field strengths in the rest
      of the interface region.

PMID- 22589114
TI  - Ionic liquid-based dispersive liquid-liquid microextraction with back-extraction
      coupled with capillary electrophoresis to determine phenolic compounds.
AB  - Ionic liquid (IL) based dispersive liquid-liquid microextraction (DLLME) with
      back-extraction coupled with capillary electrophoresis ultraviolet detection was
      developed to determine four phenolic compounds (bisphenol-A, beta-naphthol, alpha
      naphthol, 2, 4-dichlorophenol) in aqueous cosmetics. The developed method was
      used to preconcentrate and clean up the four phenolic compounds including two
      steps. The analytes were transferred into room temperature ionic liquid (1-octyl
      3-methylimidazolium hexafluorophosphate, [C(8) MIM][PF(6) ]) rich-phase in the
      first step. In the second step, the analytes were back-extracted into the
      alkaline aqueous phase. The effects of extraction parameters, such as type and
      volume of extraction solvent, type and volume of disperser, extraction and
      centrifugal time, sample pH, salt addition, and concentration and volume of NaOH
      in back-extraction were investigated. Under the optimal experimental conditions,
      the preconcentration factors were 60.1 for bisphenol-A, 52.7 for beta-naphthol,
      49.2 for alpha-naphthol, and 18.0 for 2, 4-dichlorophenol. The limits of
      detection for bisphenol-A, beta-naphthol, alpha-naphthol and 2, 4-dichlorophenol
      were 5, 5, 8, and 100 ng mL(-1), respectively. Four kinds of aqueous cosmetics
      including toner, soften lotion, make-up remover, and perfume were analyzed and
      yielded recoveries ranging from 81.6% to 119.4%. The main advantages of the
      proposed method are quick, easy, cheap, and effective.

PMID- 22589120
TI  - Effect of serum lipoproteins on stereoselective halofantrine metabolism by rat
      hepatocytes.
AB  - Experimental hyperlipidemia has shown to decrease cytochrome P450 3A4 and 2C11
      expression and to increase liver concentrations and the plasma protein binding of
      halofantrine (HF) enantiomers. The present study examined the effect of
      hyperlipidemic (HL) serum on the metabolism of HF enantiomers by primary rat
      hepatocytes. Hepatocytes from normolipidemic (NL) and HL (poloxamer 407 treated)
      rats were incubated with rac-HF in cell media with or without additional rat
      serum (5%). In those incubations with rat serum, the hepatocytes were
      preincubated or coincubated with serum from NL or HL rats. Rat serum-free
      hepatocyte incubations served as controls. Stereospecific assays were used to
      measure HF and desbutylhalofantrine (its major metabolite) enantiomer
      concentrations in whole well contents (cells + media). Concentrations of
      desbutylhalofantrine were not measurable. The disappearance (apparent metabolism)
      of (-)-HF exceeded that of antipode, but HF metabolism did not differ between
      hepatocytes from NL and HL rats. Coincubation of HL rat serum with NL hepatocytes
      caused a significant decrease in the disappearance of (-)-HF, whereas in HL
      hepatocytes, a substantially decreased apparent metabolism was noted for both
      enantiomers. Compared with NL serum, (-)-HF disappearance was significantly
      lowered upon preincubation of NL hepatocytes with HL serum. A combination of
      factors including diminished drug metabolizing or lipoprotein receptor
      expression, and increased plasma protein binding in the wells, may have
      contributed to a decrease in apparent metabolism of the HF enantiomers in the
      presence of lipoproteins from HL rat serum.

PMID- 22589121
TI  - SuperSAGE: powerful serial analysis of gene expression.
AB  - SuperSAGE is a variant of the Serial Analysis of Gene Expression (SAGE)
      technology, based on counting transcripts by sequencing analysis of short
      sequence tags. In SuperSAGE, 26 bp tags are extracted from cDNA using the Type
      III restriction endonuclease EcoP15I. The use of a longer tag size in SuperSAGE
      allows a secure tag-to-gene annotation in any eukaryotic organism. We have
      succeeded in combining SuperSAGE and high-throughput sequencing technology (Now-
      or Next-Generation Sequencing, NGS) in an approach we call High-throughput
      SuperSAGE (HT-SuperSAGE). This approach allows deep transcriptome analysis and
      multiplexing, while reducing time, cost, and effort for the analysis. In this
      chapter, we present the detailed HT-SuperSAGE protocol for both the Illumina
      Genome Analyzer and also the AppliedBiosystems SOLiD sequencer.

PMID- 22589122
TI  - Northern blot analysis for expression profiling of mRNAs and small RNAs.
AB  - Northern analysis is a conventional but gold standard method for detection and
      quantification of gene expression changes. It not only detects the presence of a
      transcript but also indicates size and relative comparison of transcript
      abundance on a single membrane. In recent years, it has been aptly adapted to
      validate and study the size and expression of small noncoding RNAs. Here, we
      describe protocols employed in our laboratory for conventional northern analysis
      with total RNA/mRNA to study gene expression and validation of small noncoding
      RNAs using low molecular weight fraction of RNAs.

PMID- 22589123
TI  - Construction of RNA-Seq libraries from large and microscopic tissues for the
      Illumina sequencing platform.
AB  - Second-generation DNA sequencing platforms have emerged as powerful tools in
      biological research. Their high sequence output at lower cost and minimal input
      DNA requirement render them suitable for broad applications ranging from gene
      expression studies to personalized clinical diagnostics. Here, we describe the
      preparation of cDNA libraries, from both whole aphid insects and their
      microscopic salivary gland tissues, suitable for high-throughput DNA sequencing
      on the Illumina platform.

PMID- 22589124
TI  - Strand-specific RNA-seq applied to malaria samples.
AB  - Over the past few years only, next-generation sequencing technologies became
      accessible and many applications were rapidly derived, such as the development of
      RNA-seq, a technique that uses deep sequencing to profile whole transcriptomes.
      RNA-seq has the power to discover new transcripts and splicing variants, single
      nucleotide variations, fusion genes, and mRNA level-based expression profiles.
      Preparing RNA-seq libraries can be delicate and usually obligates buying
      expensive kits that require large amounts of stating materials. The method
      presented here is flexible and cost-effective. Using this method, we prepared
      high-quality strand-specific RNA-seq libraries from RNA extracted from the human
      malaria parasite Plasmodium falciparum. The libraries are compatible with
      Illumina((r))'s sequencers Genome Analyzer and Hi-Seq. The method can, however,
      be easily adapted to other platforms.

PMID- 22589125
TI  - RNA in situ hybridization in Arabidopsis.
AB  - RNA in situ hybridization using digoxigenin-labeled riboprobes on tissue sections
      is a powerful technique for revealing microscopic spatial gene expression. Here,
      we describe an in situ hybridization method commonly practiced in Arabidopsis
      research labs. The highly stringent hybridization condition eliminates the usage
      of Ribonlucease A and gives highly specific signals. This also allows the use of
      longer probes which enhance signal strength without cross hybridization to
      closely related genes. In addition, using spin columns in template and riboprobe
      purification greatly reduces background signals.

PMID- 22589126
TI  - Laser microdissection of cells and isolation of high-quality RNA after
      cryosectioning.
AB  - Laser capture microdissection (LCM) has become a powerful technique that allows
      analyzing gene expression in specific target cells from complex tissues. It is
      widely used in animal research, yet few studies on plants have been carried out.
      We have applied this technique to the plants-nematode interaction by isolating
      feeding cells (giant cells; GCs) immersed inside complex swelled root structures
      (galls) induced by root-knot nematodes. For this purpose, a protocol that
      combines good morphology preservation with RNA integrity maintenance was
      developed, and successfully applied to Arabidopsis and tomato galls.
      Specifically, early developing GCs at 3 and 7 days post infection (dpi) were
      analyzed; RNA from LCM GCs was amplified and used successfully for microarray
      assays.

PMID- 22589127
TI  - Detection and quantification of alternative splicing variants using RNA-seq.
AB  - Next-generation sequencing has enabled genome-wide studies of alternative pre
      mRNA splicing, allowing for empirical determination, characterization, and
      quantification of the expressed RNAs in a sample in toto. As a result, RNA
      sequencing (RNA-seq) has shown tremendous power to drive biological discoveries.
      At the same time, RNA-seq has created novel challenges that necessitate the
      development of increasingly sophisticated computational approaches and
      bioinformatic tools. In addition to the analysis of massive datasets, these tools
      also need to facilitate questions and analytical approaches driven by such rich
      data. HTS and RNA-seq are still in a stage of very rapid evolution and are,
      therefore, only introduced in general terms. This chapter mainly focuses on the
      methods for discovery, detection, and quantification of alternatively spliced
      transcript variants.

PMID- 22589128
TI  - Separating and analyzing sulfur-containing RNAs with organomercury gels.
AB  - Polyacrylamide gel electrophoresis is a widely used technique for RNA analysis
      and purification. The polyacrylamide matrix is highly versatile for chemical
      derivitization, enabling facile exploitation of thio-mercury chemistry without
      the need of tedious manipulations and/or expensive coupling reagents, which often
      give low yields and side products. Here, we describe the use of [(N
      acryloylamino)phenyl]mercuric chloride in three-layered polyacrylamide gels to
      detect, separate, quantify, and analyze sulfur-containing RNAs.

PMID- 22589129
TI  - RNAse mapping and quantitation of RNA isoforms.
AB  - The ribonuclease protection assay (RPA) has emerged as an important methodology
      for the detection, mapping, and quantification of RNAs. In this assay, total or
      cytoplasmic RNAs are hybridized to a high-specific activity antisense radioactive
      RNA probe synthesized by in vitro transcription from the SP6 or T7 promoter of an
      appropriate linearized plasmid template by the bacteriophage SP6 or T7
      polymerase, respectively. The RNA hybrids are subjected to RNAse digestion and
      the protected products are resolved by denaturing polyacrylamide gel
      electrophoresis to allow detection of specific RNA fragments by subsequent
      autoradiography. RPAs are highly sensitive, the probes can be specifically
      targeted, and, when performed in probe excess, are quantitative, making them the
      method of choice for many analyses of RNA processing events.

PMID- 22589130
TI  - Detection and quantification of viral and satellite RNAs in plant hosts.
AB  - Northern blotting is a valuable method for detection and quantification of RNA in
      the field of virology. Although many methods including a various versions of
      polymerase chain reaction have been developed over the years, Northern blotting
      has been still considered as a useful and effective method for the analysis of
      progeny RNA accumulation for viral and subviral pathogens, such as satellite
      RNAs, in plant hosts. Here, we describe a detailed Northern blot protocol for
      efficient detection and quantification of viral and satellite RNAs from plant
      hosts.

PMID- 22589131
TI  - In situ detection of mature miRNAs in plants using LNA-modified DNA probes.
AB  - MicroRNAs (miRNAs) play important roles in development in plants, and some miRNAs
      show developmentally regulated organ- and tissue-specific expression patterns.
      Therefore, in situ detection of mature miRNAs is important for understanding the
      functions of both miRNAs and their targets. The construction of promoter-reporter
      fusions and examination of their in planta expression have been widely used and
      the results obtained thus far are rather informative; however, in some cases, the
      length of promoter that contains the entire regulatory elements is difficult to
      determine. In addition, traditional in situ hybridization with the antisense RNA
      fragment as the probe usually fails to detect miRNAs because the mature miRNAs
      are too short (~21 nt) to exhibit stable hybridization signals. In recent years,
      the locked nucleic acid (LNA)-modified DNA probe has been successfully used in
      animals and plants to detect small RNAs. Here, we describe a modified protocol
      using LNA-modified DNA probes to detect mature miRNAs in plant -tissues,
      including the design of LNA probes and detailed steps for the in situ
      hybridization experiment, using Arabidopsis miR165 as an example.

PMID- 22589132
TI  - Small RNA isolation and library construction for expression profiling of small
      RNAs from Neurospora and Fusarium using illumina high-throughput deep sequencing.
AB  - Due to crucial roles in gene regulation, noncoding small RNAs (smRNAs) of 20-30
      nucleotides (nt) have been intensively studied in mammals and plants, and are
      known to be implicated in significant diseases and metabolic disorders.
      Elucidation of biogenesis mechanisms and functional characterization of smRNAs
      are often achieved using tools, such as separation of small-sized RNA and high
      throughput sequencing. Although RNA interference pathways such as quelling and
      meiotic silencing have been well described in Neurospora crassa, knowledge of
      smRNAs in filamentous fungi is still limited compared to other eukaryotes. As a
      prerequisite for study, isolation and sequence analysis of smRNAs are necessary.
      We developed a protocol for isolation and library construction of smRNAs of 20-30
      nt for Solexa sequencing in two -filamentous fungi, N. crassa and Fusarium
      oxysporum f.sp. lycopersici. Using 200-300 MUg total RNA, smRNA was isolated by
      size fractionation, ligated with adapters, and amplified by RT-PCR for Solexa
      sequencing. Sequence analysis of several cDNA clones showed that the cloned
      smRNAs were not tRNAs and rRNAs and were fungal genome specific.

PMID- 22589133
TI  - Isolation and profiling of protein-associated small RNAs.
AB  - Small RNAs are short noncoding RNAs with important regulatory roles in many
      cellular processes. Small RNAs are generated by DICER or DICER-like proteins and
      then incorporated into RNAi effector -proteins ARGONAUTEs (AGOs) for silencing of
      their targets. In plants, small RNAs regulate host innate immunity against
      various pathogens, but their mode of action and associated protein factors that
      facilitate their function remain to be elucidated. Here, we describe an efficient
      method to isolate -AGO-associated small RNAs from Arabidopsis. This protocol can
      be easily adapted for the isolation of any protein-associated small RNAs. We
      utilized immunoprecipitation tandem with deep sequencing to identify small RNAs
      with functions in plant innate immunity. Using this described protocol, we
      identified miR393* that plays a crucial role in plant antibacterial defense. The
      distinct roles played by individual AGO proteins were observed.

PMID- 22589134
TI  - New virus discovery by deep sequencing of small RNAs.
AB  - Small RNAs (sRNAs) have emerged as one of the most important regulators of gene
      expression in eukaryotes. sRNAs are intermediate molecules as well as end
      products in the antiviral defense pathway called RNA interference in plants and
      animals. Profiling of sRNAs using next-generation sequencing technologies has
      identified a number of plant viruses that have never been reported previously,
      and has provided a deeper view of virus populations in a plant that cannot be
      achieved by conventional methods like PCR and ELISA. In this chapter, we describe
      the methodology of deep sequencing of sRNAs. The high-throughput and highly
      sensitive method will revolutionize the identification of plant viruses and the
      study of molecular plant-virus interactions.

PMID- 22589135
TI  - Global assembly of expressed sequence tags.
AB  - The method for the construction of Expressed Sequence Tag (EST) assemblies
      described here uses reads generated from 454 pyrosequencing and Sanger and
      Illumina (Solexa) sequencing technologies as input. It is consistent with and
      parallels many established EST assembly protocols, for example the TIGR Gene
      Indices. Reads that are used as input to the EST assembly process usually come
      from both internal and external sources. Thus, in addition to internally
      generated EST reads, expressed transcripts are collected from dbEST and also the
      NCBI GenBank nucleotide database (full-length and partial cDNAs). "Virtual"
      transcript sequences derived from whole genome annotation projects can be
      excluded, depending on the needs of the project. Currently, in most cases, 454
      derived sequences can be treated similar to Sanger-derived ESTs. In contrast, the
      shorter Solexa-derived sequences will have to undergo a round of either de novo
      assembly or an "align-then-assemble" approach against a reference genome, if
      available, before these transcripts can be used for the purpose of a global EST
      assembly that combines a mixture of Sanger and next-generation sequencing
      technologies.

PMID- 22589136
TI  - Computational analysis of RNA-seq.
AB  - Using High-Throughput DNA Sequencing (HTS) to examine gene expression is rapidly
      becoming a -viable choice and is typically referred to as RNA-seq. Often the
      depth and breadth of coverage of RNA-seq data can exceed what is achievable using
      microarrays. However, the strengths of RNA-seq are often its greatest weaknesses.
      Accurately and comprehensively mapping millions of relatively short reads to a
      reference genome sequence can require not only specialized software, but also
      more structured and automated procedures to manage, analyze, and visualize the
      data. Additionally, the computational hardware required to efficiently process
      and store the data can be a necessary and often-overlooked component of a
      research plan. We discuss several aspects of the computational analysis of RNA
      seq, including file management and data quality control, analysis, and
      visualization. We provide a framework for a standard nomenclature -system that
      can facilitate automation and the ability to track data provenance. Finally, we
      provide a general workflow of the computational analysis of RNA-seq and a
      downloadable package of scripts to automate the processing.

PMID- 22589137
TI  - Identification of microRNAs and natural antisense transcript-originated
      endogenous siRNAs from small-RNA deep sequencing data.
AB  - Next-generation sequencing (NGS) is becoming a routine experimental technology.
      It has been a great success in recent years to profile small-RNA species using
      NGS. Indeed, a large quantity of small-RNA profiling data has been generated from
      NGS, and computational methods have been developed to process and analyze NGS
      data for the purpose of identification of novel and expressed small noncoding
      RNAs and analysis of their roles in nearly all biological processes and pathways
      in eukaryotes. We discuss here the computational procedures and major steps for
      identification of microRNAs and natural antisense transcript-originated small
      interfering RNAs from NGS small-RNA profiling data.

PMID- 22589138
TI  - Well-being, positivity and mental health: an introduction to the special issue.
AB  - Enhancing well-being, as opposed to reducing distress, has traditionally not been
      a focus for clinical practice. There are differences in views about the nature of
      well-being, but enhancing well-being in clinical settings is a straightforward
      goal whatever concept of well-being is adopted. Reasons for adopting a well-being
      enhancing, as well as a distress-reducing, focus include the fact that many
      psychological problems do not fit the simple acute treatment model of disorder,
      that positive experience inhibits negative experience, and that people can
      benefit from therapists seeing them as more than the sum of their problems. In
      recent years, well-being has been of increasing interest to researchers and
      clinicians, and enhancing well-being is emerging as a potentially valuable
      element of effective clinical practice.

PMID- 22589139
TI  - The biologist as psychologist: Henry Fairfield Osborn's early mental ability
      investigations.
AB  - In the early 1880s, biologist Henry Fairfield Osborn conducted some of the first
      questionnaire research in American psychology. This article details how he came
      to distribute Francis Galton's questionnaire on mental imagery in the United
      States, as well as how he altered it to suit his own burgeoning psychological
      research interests. The development and circulation of questionnaires at the very
      beginning of American scientific psychology, first by Osborn and later by G.
      Stanley Hall, is discussed in terms of the new psychology's often-overlooked
      methodological plurality. Further, Osborn's late nineteenth century interest in
      individual variation and group differences in mental imagery ability are
      discussed in relation to his pervasive educational and social concerns, as well
      as his eventual status as a prominent eugenicist in the twentieth century United
      States. This research into mental imagery ability foreshadows the eugenic
      oriented intelligence testing that developed in the early twentieth century. 

PMID- 22589140
TI  - Incorporating imaging in an ROP screening practice.

PMID- 22589141
TI  - Adolescent with systemic disease and diagnostic corneal opacification. Posterior
      embryotoxon associated with Alagille syndrome.

PMID- 22589142
TI  - Simultaneous bilateral cataract surgery in children.

PMID- 22589144
TI  - Infantile nystagmus syndrome: what can FMRI tell us?

PMID- 22589145
TI  - Spectrum of myelinated nerve fibers.

PMID- 22589146
TI  - Bone involvement in aldosteronism.
AB  - In rats with aldosteronism, a reduction of bone mineral density (BMD) and
      cortical bone strength has been reported. Our study was aimed to evaluate bone
      involvement in patients with primary aldosteronism (PA). A total of 188
      consecutive subjects with adrenal incidentaloma, observed between November 2009
      and October 2011, were screened for PA with aldosterone-to-renin ratio. After
      confirmatory tests, in those who screened positive, 11 patients were diagnosed as
      PA and 15 patients were not (nPA). A serum/urinary biochemical profile,
      parathyroid hormone (PTH), BMD measured at lumbar spine (LS) and total and
      femoral neck (TN and FN) by dual X-ray absorptiometry, and conventional spinal
      radiographs (T(4) -L(4) ) were obtained in all subjects. PA patients had a
      significantly higher 24-hour urinary calcium (6.28 +/- 1.85 versus 4.28 +/- 1.18
      mmol/d; p < 0.01), and PTH (9.8 [5.8-14.6], median [range] versus 5.3 [2.5-10.8]
      pmol/L; p < 0.01) than nPA patients. BMD expressed as Z-value at LS (-1.18 +/-
      0.99 versus 0.22 +/- 1.12), FN (-0.85 +/- 0.73 versus 0.01 +/- 0.82), and TN (
      0.49 +/- 0.61 versus 0.39 +/- 0.93) was lower in PA than in nPA (p = 0.003, p =
      0.011, and p = 0.012, respectively). The prevalence of osteoporosis was higher in
      PA than in nPA (8/11, 72.7% versus 3/15, 20.0%; Fisher's exact test: p = 0.015).
      Vertebral fractures tended to be more prevalent in PA than in nPA (5/11, 45.5%
      versus 2/15, 13.3%; Fisher's exact test: p = 0.095). Logistic regression analysis
      showed that osteoporosis and morphometric vertebral fractures were associated
      with PA (odds ratio [OR], 15.4; 95% confidence interval [CI] = 1.83-130, p =
      0.012; and OR, 30.4; 95%CI, 1.07-862, p = 0.045, respectively) regardless of age,
      body mass index (BMI), and LS-BMD. In 9 of 11 PA patients, 6 months after
      beginning of treatment (surgery or spironolactone) there was a significant
      reduction of urinary calcium excretion (p < 0.01) and PTH (p < 0.01), whereas in
      5 of 11 PA patients, 1 year after beginning of treatment, BMD was significantly
      increased at LS, p < 0.01). In conclusion, PA is associated with osteoporosis,
      vertebral fractures, and increased urinary calcium excretion.

PMID- 22589147
TI  - Catalytic C-H amination with aromatic amines.
AB  - Aniline joins the club: A beta-diketiminato copper(I) catalyst enables C-H
      amination of anilines employing low catalyst loadings to preclude oxidation to
      the diazene ArN=NAr. Electron-poor anilines are particularly resistant towards
      diazene formation and participate in the amination of strong and unactivated C-H
      bonds. N-alkyl anilines also take part in C-H amination.

PMID- 22589149
TI  - Enantioselective organocatalytic Michael addition of ketones to alkylidene
      malonates.
AB  - Organocatalysts bearing sulfide or sulfone functions (1a-d) were studied for the
      direct asymmetric Michael addition of ketones and alkylidene malonates. The
      organocatalyst (S)-2-((naphthalen-2-ylthio)methyl)pyrrolidine, bearing a
      pyrrolidine and a sulfide moiety, showed a very high catalytic activity in the
      absence of additives. The reaction condition is mild, and the Michael adducts
      were obtained in very good enantioselectivities (up to 96%),
      diastereoselectivities (up to 95:5), and chemical yields (up to 95%).

PMID- 22589148
TI  - Successful reprogramming of differentiated cells by somatic cell nuclear
      transfer, using in vitro-matured oocytes with a modified activation method.
AB  - Therapeutic cloning has tremendous potential for cell therapy and tissue repair
      in some diseases. However, the efficiency of development of cloned human embryos
      by somatic cell nuclear transfer is still low. In the present study, the
      activation of cloned human embryos was investigated while using in vitro-matured
      oocytes. Pseudo-pronuclear formation and the subsequent development was compared
      with different activation parameters, including different durations of ionomycin
      and 6-dimethylaminopurine treatment. The results showed that somatic cells were
      successfully reprogrammed by modification of activation treatments while using in
      vitro-matured oocytes. The activation efficiency of cloned human embryos was
      significantly increased at durations of ionomycin at both 5 and 7 min, despite
      different durations of 6-DMAP treatment. The results of blastocyst development
      showed that 20% of activated embryos developed to the blastocyst stage when the
      embryos were activated with 5 um ionomycin for 5 min and 2 mm 6-DMAP for 5 h,
      which was significantly higher than those activated with other parameters.
      Moreover, we found that an increasing duration of 6-DMAP induced the formation of
      a single, large, pseudo-pronucleus in cloned human embryos and impaired
      subsequent development competence. In conclusion, successful reprogramming of
      human somatic cells was achieved using in vitro-matured oocytes by somatic cell
      nuclear transfer and improved with a modified activation method.

PMID- 22589150
TI  - Preparation of weak cation exchange packings for chromatographic separation of
      proteins using "click chemistry''.
AB  - "Click chemistry" is defined as a class of robust and selective chemical
      reactions affording high yields and is tolerant to a variety of solvents
      (including water), functional groups, and air. In this study, click chemistry was
      used as an effective strategy for coupling three alkyne-carboxylic acids onto the
      azide-silica to obtain three novel stationary phases of weak cation exchange
      chromatography, which were characterized with FTIR and elemental analysis. Six
      kinds of standard proteins, such as myoglobin, RNase A, RNase B, cytochrome C,
      alpha-chymotrypsin A, and lysozyme, were separated completely with the three
      novel weak cation exchange chromatography stationary phases. Compared with
      commercial weak cation exchange chromatography columns, the three kinds of novel
      weak cation exchange chromatography packings prepared by click chemistry approach
      have better resolution and selectivity. The mass recovery of more than 97% was
      obtained for all the tested proteins, and the bioactivity recovery of lysozyme on
      the prepared column was determined to be 96%. In addition, lysozyme was purified
      successfully from egg white with the novel weak cation exchange chromatography
      column by one step. The purity was more than 97% and a high specific activity was
      achieved to be 81 435 U/mg. The results illustrate the potential of click
      chemistry for preparing stationary phase for ion-exchange chromatography.

PMID- 22589151
TI  - Comprehensive evaluation of lipophilicity of biogenic amines and related
      compounds using different chemically bonded phases and various descriptors.
AB  - The retention behavior for a series of biogenic amines and related
      sympathomimetic drugs has been investigated in reversed-phase thin-layer
      chromatography using RP-2, RP-8, RP-18W, and Diol stationary phase and mixtures
      of phosphate buffer (pH = 7.10) and methanol in different proportions as mobile
      phases. Several methodologies like arithmetic mean of experimental retention
      values, extrapolation to zero methanol concentration procedure and principal
      component analysis were applied to retention data values (R(M)) in order to
      determine relevant parameters (mean of R(M) - mR(M), R(M0), and scores
      corresponding to the first principal component - PC1/R(M) respectively) encoding
      information on the lipophilic behavior of compounds. High similarities in
      lipophilicity behavior of investigated amines were highlighted by mR(M) and
      PC1/R(M) lipophilicity indices for all of the studied stationary phases. The
      experimental results were compared with some computed lipophilicity parameters
      expressed as distribution coefficients at working pH (logD), partition
      coefficients (logP(N), logP(I), and diff(logP(N-I))) concerning both neutral and
      fully protonated species and difference between both species, and also with
      various lipophilicity values (logP) generated by different commonly used
      software. Significant correlations were observed between the experimental
      lipophilicity indices mR(M) respectively PC1/R(M) and diff(logP(N-I) ) values in
      all cases.

PMID- 22589152
TI  - Ultra-high performance liquid chromatographic method for the determination of
      polycyclic aromatic hydrocarbons in a passive environmental sampler.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous compounds released in the
      environment by different sources. The aim of the present work was to validate a
      solid-phase extraction (SPE) and a rapid ultra-high performance liquid
      chromatographic (UHPLC) method for the analysis of PAHs in a passive
      environmental sampler, namely a Dacron(r) (the commercial name of a synthetic
      fiber based on polyethylene terephthalate) textile. The elution temperature was
      optimized to improve the resolution of early-eluted compounds, namely
      acenaphthene (Ac) and fluorene (F). The UHPLC method lasts about 10 min and
      showed good linearity for all the 16 PAHs considered, with regression
      coefficients over 0.99. Recoveries, limits of detection (LODs), and limits of
      quantification (LOQs) of the SPE method were well within the performance criteria
      fixed by the Regulation n. 836/2011, namely 0.3 and 0.9 MUg/kg, respectively.

PMID- 22589153
TI  - Rapid and sensitive determination of carbohydrates in foods using high
      temperature liquid chromatography with evaporative light scattering detection.
AB  - In the present work, an evaporative light scattering detector was used as a high
      temperature liquid chromatography detector for the determination of
      carbohydrates. The compounds studied were glucose, fructose, galactose, sucrose,
      maltose, and lactose. The effect of column temperature on the retention times and
      detectability of these compounds was investigated. Column heating temperatures
      ranged from 25 to 175 degrees C. The optimum temperature in terms of peak
      resolution and detectability with pure water as mobile phase and a liquid flow
      rate of 1 mL/min was 150 degrees C as it allowed the separation of glucose and
      the three disaccharides here considered in less than 3 min. These conditions were
      employed for lactose determination in milk samples. Limits of quantification were
      between 2 and 4.7 mg/L. On the other hand, a temperature gradient was developed
      for the simultaneous determination of glucose, fructose, and sucrose in orange
      juices, due to coelution of monosaccharides at temperatures higher than 70
      degrees C, being limits of quantifications between 8.5 and 12 mg/L. The proposed
      hyphenation was successfully applied to different types of milk and different
      varieties of oranges and mandarins. Recoveries for spiked samples were close to
      100% for all the studied analytes.

PMID- 22589154
TI  - Determination of disialoganglioside GD3 and monosialoganglioside GM3 in infant
      formulas and whey protein concentrates by ultra-performance liquid
      chromatography/electrospray ionization tandem mass spectrometry.
AB  - A method of ultra-performance liquid chromatography combined with electrospray
      ionization triple quadrupole tandem mass spectrometry (UPLC-ESI-MS/MS) has been
      established for simultaneous determination of major disialoganglioside 3 (GD3)
      and monosialoganglioside 3 (GM3) in infant formulas and whey protein
      concentrates. Gangliosides were extracted by using the technique of Svennerholm
      and Fredman and then cleaned up with OASIS HLB solid-phase extraction (SPE)
      cartridges. The various molecular species of gangliosides were separated on an
      Acquity UPLC BEH C8 column and analyzed under the negative ion mode. GD3 and GM3
      were rapidly quantified using internal standard (IS) method. The developed method
      was further validated by determining the linearity, average recovery, sensitivity
      (limit of quantification), and precision. The results presented high correlation
      coefficients (R(2)  > 0.993) of the selected 16 gangliosides molecular species
      and provided the respective linear ranges. The limit of quantification was 0.325
      0.734 mg/100 g for eight molecular species of GD3 and 0.008-0.312 mg/100 g for
      eight molecular species of GM3, respectively. The reasonable average recoveries
      (81-95%) and precision (relative standard deviation [RSD] <=15%) were also
      demonstrated in three different spiked levels. This new method would be very
      useful in the quantitative determination of gangliosides in infant formulas and
      whey protein concentrates.

PMID- 22589155
TI  - Adsorption in a stratified column bed packed with porous particles having
      partially fractal structures and a distribution of particle diameters.
AB  - Stratified column bed systems whose sections are formed by packing adsorbent
      particles with a partially fractal structure are proposed and studied. The
      simulation results clearly show that the breakthrough times and the shape of the
      breakthrough curves obtained from stratified column beds are significantly larger
      and sharper than those obtained from conventional columns. The stratified column
      beds provide, to the designer and user of chromatographic column systems, more
      degrees of freedom with respect to the number of parameters and variables that
      could be controlled in the design, construction, and operation of efficient
      chromatographic adsorption systems. Furthermore, the results suggest that the
      stratified column beds could provide a higher dynamic adsorptive capacity than
      conventional columns when it is required to increase the column throughput.

PMID- 22589156
TI  - Monolithic columns with optimized pore structure for molecular size-based
      separations of synthetic polymers.
AB  - Monolithic capillary columns based on divinylbenzene were synthesized using
      different alcanols as porogens. Prepared columns were tested in separation of
      polystyrene standards according to their molar mass (MM) and were characterized
      by corresponding calibration graphs. It was demonstrated that a decrease of
      alcanol chain length from dodecanol to octanol resulted in a decrease of column
      permeability and in an improved column ability to separate polystyrene standards.
      In contrast, removing a good solvent from porogen mixture results in an increase
      of column permeability and in a decrease of column performance toward polystyrene
      standards. Optimized synthetic conditions included porogen composed of nonanol
      and toluene or mesytilene, and the column prepared with this porogen was capable
      of separating a mixture of 14 polystyrene standards with MM ranged from several
      millions to oligomers.

PMID- 22589157
TI  - Modeling gradient elution in countercurrent chromatography: efficient separation
      of tanshinones from Salvia miltiorrhiza Bunge.
AB  - Countercurrent chromatography (CCC) is a support-free liquid-liquid
      chromatography using centrifugal fields to hold the liquid stationary phase. CCC
      has been widely applied in the separation of various natural and synthetic
      components using a variety of biphasic liquid systems. The related hexane or
      heptane/ethyl acetate/methanol or ethanol/water biphasic liquid systems
      demonstrated their significance in CCC. Gradient is difficult in CCC since any
      composition change in one phase induces a composition change of the other phase
      to maintain phase equilibrium. This work provides a new insight into linear
      gradient elution in CCC that is feasible with some biphasic liquid systems such
      as selected compositions of the hexane/ethyl acetate/ethanol/water systems. The
      equations modeling solute motion inside the CCC column are proposed. Particular
      compositions of the liquid system, namely the hexane/ethyl acetate/ethanol/water
      8:2:E:W compositions with E + W = 10, were studied from W = 1 to 9. They showed
      moderate changes in the upper organic phase compositions. The model is tested
      with the separation of tanshinones from the rhizome of Salvia miltiorrhiza Bunge.
      Different linear solvent gradient profiles were experimentally performed between
      8:2:5:5 and 8:2:3:7 compositions and the results were evaluated using the
      proposed model. Five tanshinones including dihydrotanshinone I, cryptotanshinone,
      tanshinone I, 1,2-dihydrotanshinquinone, and tanshinone IIA have been
      successfully separated (>95% purities) using a gradient profile optimized by the
      developed model. The gradient model can be used only with biphasic liquid systems
      in which one phase shows minimum composition changes when the other phase
      composition changes notably. This case is not the general case for biphasic
      liquid systems but can be applied with specific compositions of the quaternary
      hexane or heptane/ethyl acetate/methanol or ethanol/water most useful CCC liquid
      systems.

PMID- 22589158
TI  - Bioassay-guided isolation of antioxidants from Astragalus altaicus by combination
      of chromatographic techniques.
AB  - An efficient method for bioassay-guided preparative isolation of antioxidants
      from the n-butanol extract of Astragalus altaicus Bunge was ingeniously developed
      by combination of silica gel column chromatography and high-speed counter-current
      chromatography. Under the bioassay-guidance of antioxidant activities, the
      antioxidants were gradually separated from the crude sample of Astragalus
      altaicus Bunge by silica gel column chromatography and high-speed counter-current
      chromatography. Silica gel column chromatography separation was performed with
      chloroform, chloroform-methanol (100:1~5:1, v/v) and chloroform-methanol-water
      (5:1:0.1~2:1:0.1, v/v/v). High-speed counter-current chromatography separation
      was performed with a two-phase solvent system composed of ethyl acetate-n-butanol
      water (2:1:6, v/v/v), which was successfully selected by thin layer
      chromatography analysis, at a flow rate of 1.5 mL/min. As a result, isorhamnetin
      3-gentiobioside (20.8 mg), rutin (82.0 mg), and narcissin (12.8 mg) were obtained
      for the first time from 200 mg of the crude sample, ABS-5 of Astragalus altaicus
      Bunge. The purities were all at over 95% by high-performance liquid
      chromatography analysis, and their structures were unambiguously identified by
      mass spectroscopy, (1) H, and (13) C nuclear magnetic resonance spectroscopy.
      Antioxidant activities of the three compounds were also assayed by in vitro ABTS
      [2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) diamonium salt] radical
      cation scavenging activity. Among them, rutin possessed the highest antioxidant
      capacity with SC(50) value of 22.15 MUg/mL.

PMID- 22589159
TI  - Simultaneous determination of six isoflavonoids in rat plasma after
      administration of total flavonoid from Gegen by ultra-HPLC-MS/MS.
AB  - A simple, specific, and sensitive ultra-performance liquid chromatography-tandem
      mass spectrometry method was developed for the simultaneous determination of 3'
      hydroxypuerarin, 6''-O-xylosylpuerarin, mirificin, puerarin, 3'-methoxypuerarin
      and daidzin in rat plasma. After the addition of methanol containing 0.1% formic
      acid and 10% ascorbic acid, the analytes and rutoside were obtained by protein
      precipitation, then separated on a Thermo Syncronis C18 column (2.1 mm * 10 cm,
      1.7 MUm) by gradient elution and monitored using an electrospray ionization
      interface operating in positive ion and selective reaction monitoring acquisition
      mode. The calibration curves of these analytes showed good linearity (r > 0.99)
      within the test ranges. The lower limit of quantification was 0.0200 MUg/mL for
      3'-hydroxypuerarin, 0.0101 MUg/mL for 6''-O-xylosylpuerarin, 0.0100 MUg/mL for
      mirificin and puerarin, 0.0098 MUg/mL for 3'-methoxypuerarin, and 0.0090 MUg/mL
      for daidzin. The intraday and interday precision and accuracy were all within
      15%. The extraction recoveries were from 74.0 to 95.8%. The validated method was
      successfully applied to pharmacokinetic studies of the six isoflavonoids in rat
      plasma after intravenous administration of total flavonoids from Gegen.

PMID- 22589160
TI  - Open-tubular capillary electrochromatography with bare gold nanoparticles-based
      stationary phase applied to separation of trypsin digested native and glycated
      proteins.
AB  - In this work, open-tubular capillary electrochromatography (OT-CEC) method with
      bare gold nanoparticles (GNPs)-based stationary phase has been developed and
      applied for separation of tryptic peptide fragments of native and glycated
      proteins, bovine serum albumin (BSA), and human transferrin (HTF). The GNPs-based
      stationary phase was prepared by immobilization of bare GNPs, freshly reduced
      from tetrachloroaurate(III) ions by citrate reduction, on the sol-gel pretreated
      inner wall of the fused silica capillary. The separation efficiency, peak
      capacity, and peptide recovery of this open-tubular capillary column were
      investigated by varying the experimental parameters such as type and
      concentration of the buffering constituent and pH of the background electrolyte
      (BGE), temperature, and separation voltage. The best separations of the above
      tryptic peptides were achieved in the BGE composed of aqueous 100 mmol/L sodium
      phosphate buffer, pH 2.5, at separation voltage 10 kV per 47-cm long, 50 MUm
      inside diameter capillary thermostated at 25 degrees C. OT-CEC with bare GNPs
      stationary phase is shown to be a suitable technique for separation of complex
      peptide mixtures arising from tryptic digestion of native and glycated BSA and
      HTF, and for investigation of glycation (nonenzymatic glycosylation) of these
      proteins.

PMID- 22589161
TI  - Simultaneous determination of dihydroxybenzene positional isomers by capillary
      electrochromatography using gold nanoparticles as stationary phase.
AB  - The paper describes the enhanced separation of o-, m-, p-dihydroxybenzene by
      capillary electrochromatography (CEC) using gold nanoparticles (AuNPs) as
      stationary phase. The effect of the AuNPs concentration upon separation was
      investigated. The experimental parameters, including separation voltage, pH, and
      concentration of running buffer, were optimized. Under the optimum conditions, a
      good resolution of three dihydroxybenzene isomers was obtained within 15 min in a
      50 cm effective length capillary modified with 0.02 nmol/L AuNPs at a separation
      voltage of 16 kV in a 50 mmol/L acetate buffer (pH 5.0). The linear ranges were
      from 10(-6)  to 10(-4)  mol/L and the detection limits were as low as 10(-7) 
      mol/L. This method was successfully used to analysis two kinds of hair coloring
      agent sample with recoveries in the range of 90-105% and relative standard
      deviations (RSD) less than 5.0%.

PMID- 22589162
TI  - Polymethacrylate-based monolithic capillary column with weak cation exchange
      functionalities for capillary electrochromatography.
AB  - Polymethacrylate-based monolith with weak cation exchange functionalities was
      prepared in capillary column (i.d. 100 MUm, o.d. 375 MUm) by in situ
      polymerization of butyl methacrylate, ethylene dimethacrylate and N-methacryloyl
      L-glutamic acid in presence of porogens. The porogen mixture included N,N
      dimethyl formamide and phosphate buffer. The preparation procedure of stationary
      phase contained the synthesis of monomer, silanization of capillary inner wall
      and in situ polymerization. The use of amino acid based monomer for the monolith
      synthesis is one of the originalities of this novel approach. N-methacryloyl-L
      glutamic acid has two carboxyl functionalities. The separation of the solutes
      were performed at different acetonitrile/phosphate buffer and acetonitrile/sodium
      hydroxide contents. The applied voltage for the alkyl benzenes was changed
      between +5 and +30 kV. CEC separations of alkyl benzenes, acidic, basic, phenolic
      and some polycylic aromatic compounds were succesfully performed under capillary
      electrochromatography mode with cathodic electroosmotic flow.

PMID- 22589163
TI  - Full automatic determination of chlorophenols in water using solid-phase
      microextraction/on-fiber derivatization and gas chromatography-mass spectrometry.
AB  - A fully automated combination of solid-phase microextraction and on-fiber
      derivatization coupled with gas chromatography-mass spectrometry was developed to
      determine 17 chlorophenols in aqueous samples. Optimal parameters for the
      automated process, such as fiber coating (polyacrylate), derivatization reagent
      (N,O-bis(trimethylsilyl) trifluoroacetamide), extraction time (60 min),
      derivatization time (5 min), incubation temperature (35 degrees C), sample pH
      (3), and ionic strength (300 g L(-1) of NaCl), as well as desorption time (5 min)
      and desorption temperature (270 degrees C) were established. The whole procedure
      took only 90 min and was performed automatically. The shortcomings of silylation
      derivatives, like incompleteness and instability, were overcome by using solid
      phase microextraction on-fiber silylation in this study. The results from both
      pure water and river water samples showed that the method had a good linearity
      (r(2) = 0.9993-1.0000), ranging from 0.01 to 100 MUg L(-1). The related standard
      deviations were between 3.6 and 10.0%. The limits of detections and
      qualifications ranged from 0.03 to 3.11 ng L(-1) and 0.09 to 10.4 ng L(-1) for
      the CPs, respectively. The proposed method is superior to traditional solid phase
      extraction procedure.

PMID- 22589164
TI  - Dispersive liquid-liquid microextraction combined with gas chromatography for
      extraction and determination of class 1 residual solvents in pharmaceuticals.
AB  - The present study reports a new method for analyzing class 1 residual solvents
      (RSs), 1,1-dichloroethene (1,1-DCE), 1,2-dichloroethane (1,2-DCE), 1,1,1
      trichloroethane (1,1,1-TCE), carbon tetrachloride (CT), and benzene (Bz), in
      pharmaceutical products using dispersive liquid-liquid microextraction (DLLME)
      combined with gas chromatography-flame ionization detection (GC-FID). Unlike
      common DLLME methods, solvents of high boiling point were selected as dispersive
      and extraction solvents in order to prevent their chromatographic peaks from
      overlapping with those of analytes that have short retention times. Therefore N,N
      dimethyl formamide (DMF) and 1,2-dibromoethane (1,2-DBE) were chosen as
      dispersive and extraction solvents, respectively. Analytical parameters of the
      proposed method were determined and good linearities and broad linear ranges
      (LRs) were obtained. Taking 500 mg samples, limit of detections for the tested
      pharmaceuticals were obtained as 0.11, 0.03, 0.05, 0.05, and 0.006 MUg g(-1)  for
      CT, 1,1-DCE, 1,2-DCE, 1,1,1-TCE, and Bz, respectively, which are considerably
      much lower than their permissible limits in pharmaceuticals.

PMID- 22589165
TI  - Highly selective stir bar coated with dummy molecularly imprinted polymers for
      trace analysis of bisphenol A in milk.
AB  - A water compatible molecularly imprinted polymers (MIPs) coated stir bar for
      bisphenol A(BPA) was prepared with 3,3',5,5'-tetrabromobisphenol A as the dummy
      template molecule in this study. The dummy molecularly imprinted polymers coated
      stir bar (DMIPs-SB) showed better selectivity than the bars coated with
      polydimethylsiloxane or non-imprinted polymers when used to extract BPA and its
      three analogues. The saturated adsorption amount of the DMIPs coating was 3.0
      times over that of the non-imprinted polymers coating. To achieve the optimum
      extraction performance, several parameters, including extraction and desorption
      time, pH value, adsorption temperature and stirring speed were investigated. The
      high-performance liquid chromatography combined with the DMIPs-SB was employed in
      the analysis of BPA in aqueous solution. The linear range of BPA concentration in
      aqueous medium was 0.0228-2.28 ng/mL with correlation coefficient of 0.9994 and
      the detection limit was about 6.84 * 10(-3)  ng/mL based on three times ratio of
      signal to noise. This method was directly applied to the determination of trace
      BPA in milk with satisfactory results.

PMID- 22589166
TI  - Solid phase extraction of petroleum carboxylic acids using a functionalized
      alumina as stationary phase.
AB  - Petroleum essentially consists of a mixture of organic compounds, mainly
      containing carbon and hydrogen, and, in minor quantities, compounds with
      nitrogen, sulphur, and oxygen. Some of these compounds, such as naphthenic acids,
      can cause corrosion in pipes and equipment used in processing plants. Considering
      that the methods of separation or clean up the target compounds in low
      concentrations and in complex matrix use large amounts of solvents or stationary
      phases, is necessary to study new methodologies that consume smaller amounts of
      solvent and stationary phases to identify the acid components present in complex
      matrix, such as crude oil samples. The proposed study aimed to recover acid
      compounds using the solid phase extraction method, employing different types of
      commercial stationary ion exchange phases (SAX and NH(2)) and new phase alumina
      functionalized with 1,4-bis(n-propyl)diazoniabicyclo[2.2.2]octane chloride
      silsesquioxane (Dab-Al(2)O(3)), synthesized in this work. Carboxylic acids were
      used as standard mixture in the solid phase extraction for further calculation of
      recovery yield. Then, the real sample (petroleum) was fractionated into
      saturates, aromatics, resins, and asphaltenes, and the resin fraction of
      petroleum (B1) was eluted through stationary ion exchange phases. The stationary
      phase synthesized in this work showed an efficiency of ion exchange comparable to
      that of the commercial stationary phases.

PMID- 22589167
TI  - Effective separation of dopamine from bananas on 2-(3,4
      dimethoxyphenyl)ethylamine imprinted polymer.
AB  - A 2-(3,4-dimethoxyphenyl)ethylamine imprinted polymer (MIP(pt) ) was prepared via
      the precipitation polymerization together with a nonimprinted polymer (NIP). The
      morphology of particles was investigated by scanning electron microscopy and the
      specific surface areas were estimated by methylene blue adsorption (60.5 +/- 3.5
      and 36.9 +/- 1.2 m(2)/g for MIP(pt) and NIP, respectively). The binding
      experiments were performed to determine the binding capacity of MIP(pt)/NIP
      particles toward dopamine. Next, the effects of solvents on loading, washing, and
      eluting steps were examined on solid-phase extraction (SPE). Methanol-water 85:15
      v/v (loading step), methanol (washing step), and 0.04 M aqueous ammonium acetate
      methanol 30:70 v/v (eluting step) were selected as the most effective systems.
      Described SPE protocol was successfully applied for separation of dopamine on 2
      (3,4-dimethoxyphenyl)ethylamine imprinted particles. Finally, the molecularly
      imprinted polymer was used for determination of dopamine in spiked banana
      extract. The total recovery of dopamine from MIP(pt) was equal to 88.5 +/- 4.6%,
      but from NIP was only 12.8 +/- 2.3%. The developed material and method were
      demonstrated to be applicable for the separation of dopamine from bananas. The
      commercial sorbent C18 was not suitable to such application.

PMID- 22589170
TI  - Perinatal outcomes of fetal echogenic bowel.
AB  - OBJECTIVE: To investigate perinatal outcomes of fetal echogenic bowel (FEB).
      METHOD: This is a retrospective observational study of FEB cases from Jan 2005
      Dec 2010. Data from ultrasound and fetal medicine investigations, uterine artery
      Doppler (UAD), intra-partum care and neonatal outcome were obtained from Fetal
      Medicine, Obstetric and Neonatal Databases. RESULTS: There were 139 cases
      presenting at 21(+5) (15(+1) -35(+5) ) weeks gestation. Overall, 106/139 (76.2%)
      were live born (LB), 8/139 (5.8%) were complicated by intra-uterine deaths (IUD),
      11/139 (7.9%) had termination of pregnancy (TOP) and 14/139 (10.1%) were lost to
      follow-up after 28 weeks gestation. Six had chromosomal/genetic abnormalities,
      two had congenital cytomegalovirus, none had cystic fibrosis.Uterine artery
      Doppler was normal in 106/130 (81.5%) cases. In this group, there were no cases
      of fetal growth restriction (FGR), 95/106 (89.6%) were LB, 1/106 (0.94%) had an
      IUD. In the abnormal UAD group, 17/24 (70.1%) developed FGR, 11/24 (45.8%) were
      LB, 4/24 (16.7%) had TOP, 7/24 (29.2%) had IUD.In total, 20/106 (18.9%) live
      births were admitted for specialist neonatal care, 12/20 (60%) for prematurity.
      Only one had primary bowel pathology. CONCLUSION: Pregnancies with FEB and screen
      positive UAD are at risk of adverse perinatal outcome. Primary bowel pathology is
      rare following the finding of FEB.

PMID- 22589171
TI  - Mesoporous nickel oxide nanowires: hydrothermal synthesis, characterisation and
      applications for lithium-ion batteries and supercapacitors with superior
      performance.
AB  - Mesoporous nickel oxide nanowires were synthesized by a hydrothermal reaction and
      subsequent annealing at 400  degrees C. The porous one-dimensional nanostructures
      were analysed by field-emission SEM, high-resolution TEM and N(2) 
      adsorption/desorption isotherm measurements. When applied as the anode material
      in lithium-ion batteries, the as-prepared mesoporous nickel oxide nanowires
      demonstrated outstanding electrochemical performance with high lithium storage
      capacity, satisfactory cyclability and an excellent rate capacity. They also
      exhibited a high specific capacitance of 348 F g(-1)  as electrodes in
      supercapacitors.

PMID- 22589174
TI  - LRP8 mediates Wnt/beta-catenin signaling and controls osteoblast differentiation.
AB  - The Wnt/beta-catenin signaling pathway plays a pivotal role in regulating
      osteoblast differentiation and bone formation. Here, we identify low-density
      lipoprotein (LDL) receptor-related protein 8 (LRP8) as a positive regulator of
      Wnt/beta-catenin signaling. In a small interfering RNA (siRNA) screen, LRP8 was
      shown to be required for Wnt/beta-catenin-induced transcriptional reporter
      activity. We found that ectopic expression of LRP8 increased Wnt-induced
      transcriptional responses, and promoted Wnt-induced beta-catenin accumulation.
      Moreover, knockdown of LRP8 resulted in a decrease in beta-catenin levels and
      suppression of Wnt/beta-catenin-induced Axin2 transcription. Functional studies
      in KS483 osteoprogenitor cells showed that LRP8 depletion resulted in impaired
      activation of endogenous Wnt-induced genes and decreased osteoblast
      differentiation and mineralization, whereas LRP8 ectopic expression had the
      opposite effect. These results identify LRP8 as a novel positive factor of
      canonical Wnt signaling pathway and show its involvement in Wnt-induced
      osteoblast differentiation.

PMID- 22589172
TI  - Evaluation of Citrus aurantifolia peel and leaves extracts for their chemical
      composition, antioxidant and anti-cholinesterase activities.
AB  - BACKGROUND: The replacement of synthetic antioxidants by safe natural
      antioxidants fosters research on the screening of vegetables and food as sources
      of new antioxidants. Moreover, oxidative degeneration of cells is associated with
      neurodegenerative diseases such as Alzheimer's disease. On the basis of these
      considerations this work aimed to investigate the antioxidant properties [by
      using the diphenyl picryl hydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6
      sulfonic acid) and ferric reducing ability of plasma assays, and the beta
      carotene bleaching test] and the anti-cholinesterase activity of Citrus
      aurantifolia peel and leaves from different areas of growth. RESULTS: Methanol
      extracts of the peel and leaves demonstrated the strongest radical scavenging
      activity. A similar trend was observed with the reducing ability, with values
      from 112.1 to 146.0 umol L(-1) Fe(II) g(-1). The relationship between phenol and
      flavonoid contents and antioxidant activity was statistically investigated. Based
      on analysis by high-performance liquid chromatography, the most abundant
      flavonoids found in C. aurantifolia extracts were apigenin, rutin, quercetin,
      kaempferol and nobiletin. n-Hexane fractions of both peel and leaves showed a
      good acetylcholinesterase inhibitory activity with IC(50) values in the range
      91.4-107.4 ug mL(-1). Gas chromatography-mass spectrometry analysis revealed the
      presence of monoterpenes and sesquiterpenes as most common components.
      CONCLUSION: The findings of this study suggest a potential use of C. aurantifolia
      peel and leaves for supplements for human health.

PMID- 22589175
TI  - Repair of surgically created diaphragmatic defect in rat with use of a
      crosslinked porous collagen scaffold.
AB  - Large defects in congenital diaphragmatic hernia are closed by patch repair,
      which is associated with a high complication risk and reherniation rate. New
      treatment modalities are warranted. We evaluated the feasibility of using an
      acellular biodegradable collagen bioscaffold for a regenerative medicine approach
      to close a surgically created diaphragmatic defect in a rat model. Scaffold
      degradation, cellular ingrowth and regeneration of the diaphragm were studied. In
      25 rats, a subcostal incision was made and one third of the right hemidiaphragm
      was resected. Crosslinked porous type I collagen scaffolds (O ~ 14 mm) were
      sutured into the lesion. Rats were sacrificed at 2, 4, 8, 12 or 24 weeks after
      scaffold implantation. Implants were evaluated macroscopically and
      (immuno)histologically. Survival after surgery was 88% with no evidence of
      reherniation. Histological examination showed that the collagen scaffold degraded
      slowly and new collagen, elastin and mesothelium were deposited. Blood vessels
      were observed primarily at the outer borders of the scaffold; their number
      gradually increased in time. Muscle fibres were found on the scaffold covering up
      to 10% of the defect. Macroscopically, adhesion of the scaffold to the liver was
      observed. Use of a collagen scaffold to close a surgically created diaphragmatic
      defect is feasible, with evidence of new tissue formation. The use of crosslinked
      collagen scaffolds allows targeted modification; e.g. addition of growth factors
      to further stimulate growth of muscle cells.

PMID- 22589176
TI  - Do cement nanotubes exist?
AB  - Using atomistic simulations, this work indicates that cement nanotubes can exist.
      The chemically compatible nanotubes are constructed from the two main minerals in
      ordinary Portland cement pastes, namely calcium hydroxide and a calcium silicate
      hydrate called tobermorite. These results show that such nanotubes are stable and
      have outstanding mechanical properties, unique characteristics that make them
      ideally suitable for nanoscale reinforcements of cements.

PMID- 22589179
TI  - Enhanced identification of peptides lacking basic residues by LC-ESI-MS/MS
      analysis of singly charged peptides.
AB  - Peptide sequences lacking basic residues (arginine, lysine, or histidine,
      referred to as "base-less") are of particular importance in proteomic experiments
      targeting protein C-termini or employing nontryptic proteases such as GluC or
      chymotrypsin. We demonstrate enhanced identification of base-less peptides by
      focused analysis of singly charged precursors in liquid chromatography (LC)
      electrospray ionization (ESI) tandem mass spectrometry (MS/MS). Singly charged
      precursors are often excluded from fragmentation and sequence analysis in LC
      MS/MS. We generated different pools of base-less and base-containing peptides by
      tryptic and nontryptic digestion of bacterial proteomes. Focused LC-MS/MS
      analysis of singly charged precursor ions yielded predominantly base-less peptide
      identifications. Similar numbers of base-less peptides were identified by LC-MS/M
      Sanalysis targeting multiply charged precursors. There was little redundancy
      between the base-less sequences derived by both MS/MS schemes. In the present
      experimental outcome, additional LC-MS/MS analysis of singly charged precursors
      substantially increased the identification rate of base-less sequences derived
      from multiply charged precursors. In conclusion, LC-MS/MS based identification of
      base-less peptides is substantially enhanced by additional focused analysis of
      singly charged precursors.

PMID- 22589180
TI  - Digital microfluidic hydrogel microreactors for proteomics.
AB  - Proteolytic digestion is an essential step in proteomic sample processing. While
      this step has traditionally been implemented in homogeneous (solution) format,
      there is a growing trend to use heterogeneous systems in which the enzyme is
      immobilized on hydrogels or other solid supports. Here, we introduce the use of
      immobilized enzymes in hydrogels for proteomic sample processing in digital
      microfluidic (DMF) systems. In this technique, preformed cylindrical agarose
      discs bearing immobilized trypsin or pepsin were integrated into DMF devices. A
      fluorogenic assay was used to optimize the covalent modification procedure for
      enzymatic digestion efficiency, with maximum efficiency observed at 31 MUg
      trypsin in 2-mm diameter agarose gel discs. Gel discs prepared in this manner
      were used in an integrated method in which proteomic samples were sequentially
      reduced, alkylated, and digested, with all sample and reagent handling controlled
      by DMF droplet operation. Mass spectrometry analysis of the products revealed
      that digestion using the trypsin gel discs resulted in higher sequence coverage
      in model analytes relative to conventional homogenous processing. Proof-of
      principle was demonstrated for a parallel digestion system in which a single
      sample was simultaneously digested on multiple gel discs bearing different
      enzymes. We propose that these methods represent a useful new tool for the
      growing trend toward miniaturization and automation in proteomic sample
      processing.

PMID- 22589181
TI  - An improved quantitative mass spectrometry analysis of tumor specific mutant
      proteins at high sensitivity.
AB  - New disease specific biomarkers, especially for cancer, are urgently needed to
      improve individual diagnosis, prognosis, and treatment selection, that is, for
      personalized medicine. Genetic mutations that affect protein function drive
      cancer. Therefore, the detection of such mutations represents a source of cancer
      specific biomarkers. Here we confirm the implementation of the mutant protein
      specific immuno-SRM (where SRM is selective reaction monitoring) mass
      spectrometry method of RAS proteins reported by Wang et al. [Proc. Natl. Acad.
      Sci. USA 2011, 108, 2444-2449], which exploits an antibody to simultaneously
      capture the different forms of the target protein and the resolving power and
      sensitivity of LC-MS/MS and improve the technique by using a more sensitive mass
      spectrometer. The mutant form G12D was quantified by SRM on a QTRAP 5500 mass
      spectrometer and the MIDAS workflow was used to confirm the sequence of the
      targeted peptides. This assay has been applied to quantify wild type and mutant
      RAS proteins in patient tumors, xenografted human tissue, and benign human
      epidermal tumors at high sensitivity. The limit of detection for the target
      proteins was as low as 12 amol (0.25 pg). It requires low starting amounts of
      tissue (ca.15 mg) that could be obtained from a needle aspiration biopsy. The
      described strategy could find application in the clinical arena and be applied to
      the study of expression of protein variants in disease.

PMID- 22589183
TI  - PRDB: Protein Repeat DataBase.
AB  - Rapidly increasing genomic data present new challenges for scientists: making
      sense of millions of amino acid sequences requires a systematic approach and
      information about their 3D structure, function, and evolution. Over the last
      decade, numerous studies demonstrated the fundamental importance of protein
      tandem repeats and their involvement in human diseases. Bioinformatics analysis
      of these regions requires special computer programs and databases, since the
      conventional approaches predominantly developed for globular domains have limited
      success. To perform a global comparative analysis of protein tandem repeats, we
      developed the Protein Tandem Repeat DataBase (PRDB). PRDB is a curated database
      that includes the protein tandem repeats found in sequence databanks by the T
      REKS program. The database is available at
      http://bioinfo.montp.cnrs.fr/?r=repeatDB.

PMID- 22589182
TI  - Ultra-high intra-spectrum mass accuracy enables unambiguous identification of
      fragment reporter ions in isobaric multiplexed quantitative proteomics.
AB  - Isobaric tagging using reagents such as tandem mass tags (TMT) and isobaric tags
      for relative and absolute quantification (iTRAQ) have become popular tools for
      mass spectrometry based quantitative proteomics. Because the peptide
      quantification information is collected in tandem mass spectra, the accuracy and
      precision of this method largely depend on the resolution with which precursor
      ions can be selected for the fragmentation and the specificity of the generated
      reporter ion. The latter can constitute an issue if near isobaric ion signals are
      present in such spectra because they may distort quantification results. We
      propose a simple remedy for this problem by identifying reporter ions via the
      accurate mass differences within a single tandem mass spectrum instead of
      applying fixed mass error tolerances for all tandem mass spectra. Our results
      show that this leads to unambiguous reporter ion identification and complete
      removal of interfering signals. This mode of data processing is easily
      implemented in software and offers advantages for protein quantification based on
      few peptides.

PMID- 22589184
TI  - MALDI-TOF-MS analysis of sialylated glycans and glycopeptides using 4-chloro
      alpha-cyanocinnamic acid matrix.
AB  - For MALDI analysis of glycans and glycopeptides, the choice of matrix is crucial
      in minimizing desialylation by mass spectrometric in-source and metastable decay.
      Here, we evaluated the potential of 4-chloro-alpha-cyanocinnamic acid (Cl-CCA)
      for MALDI-TOF-MS analysis of labile sialylated tryptic N-glycopeptides and
      released N- and O-glycans. Similar to DHB, but in contrast to CHCA, the Cl-CCA
      matrix allowed the analysis of sialylated N-glycans and glycopeptides in negative
      ion mode MALDI-TOF-MS. Dried droplet preparations of Cl-CCA provided
      microcrystals with a homogeneous spatial distribution and high shot-to-shot
      repeatability similar to CHCA, which simplified the automatic measurement and
      improved the resolution and mass accuracy. Interestingly, reflectron-positive ion
      mode analysis of 1-phenyl-3-methyl-5-pyrazolone (PMP)-labeled O-glycans with Cl
      CCA revealed more complete profiles than with DHB and CHCA. In conclusion, we
      clearly demonstrate the high potential of this rationally designed matrix for
      glycomics and glycoproteomics.

PMID- 22589185
TI  - Impaired ubiquitin-proteasome-mediated PGC-1alpha protein turnover and induced
      mitochondrial biogenesis secondary to complex-I deficiency.
AB  - Most eukaryotic cells depend on mitochondrial OXidative PHOSphorylation (OXPHOS)
      in their ATP supply. The cellular consequences of OXPHOS defects and the
      pathophysiological mechanisms in related disorders are incompletely understood.
      Using a quantitative proteomics approach we provide evidence that a genetic
      defect of complex-I of the OXPHOS system may associate with transcriptional
      derangements of mitochondrial biogenesis through stabilization of the master
      transcriptional regulator PPARgamma co-activator 1alpha (PGC-1alpha) protein.
      Chronic oxidative stress suppresses the gene expression of PGC-1alpha but
      concomitant inhibition of the ubiquitin-proteasome system (UPS) can stabilize
      this co-activator protein, thereby inducing its downstream metabolic gene
      expression programs. Thus, mitochondrial biogenesis, which lays at the heart of
      the homeostatic control of energy metabolism, can be deregulated by secondary
      impairments of the protein turnover machinery.

PMID- 22589187
TI  - Protein alteration of HepG2.2.15 cells induced by iron overload.
AB  - Hepatitis B can progress into hepatocellular carcinoma. Body irons may interfere
      with the clearance of hepatitis B virus (HBV) and contribute to genesis of tumor.
      To investigate the role of iron played in HBV-related pathogenesis, here we
      studied the effect of iron with different concentrations and valence states on
      growth of HepG2.2.15 cells and secretion of virus proteins. A strong tolerance of
      HepG2.2.15 cells to iron challenge was found. The concentration of hepatitis B
      surface antigen in cell culture medium was decreased after iron stimulation.
      Lower concentrations of iron facilitated hepatitis B e-antigen (HBeAg) secretion.
      Fe(2+)  appeared more effective on HBeAg secretion than Fe(3+)  did. In parallel,
      the differential protein profiles in HepG2.2.15 cells were studied by iTRAQ and
      LC-MS/MS. The differentially expressed proteins were mainly involved in stress
      response, signal transduction, apoptosis, etc. Four proteins (14-3-3 beta/alpha,
      VCP, migration inhibitory factor, and Nup153) were verified by Western-blotting
      and found to be consistent with the iTRAQ data. Interestingly, nuclear import of
      Nuclear factor kappa B (NFkappaB) and its activity were found to be affected by
      the decreased Nup153 in iron stimulated HepG2.2.15 cells. The results may
      indicate possible molecular mechanism how the synergism of HBV and iron
      stimulation damages host liver cells.

PMID- 22589186
TI  - Proteomic identification of E6AP as a molecular target of tamoxifen in MCF7
      cells.
AB  - Tamoxifen (Tam) is most widely used selective estrogen receptor modulator (SERM)
      for treatment of hormone-responsive breast cancer. Despite being regularly used
      in clinical therapy for breast cancer since 1971, the mechanism of Tam action
      remains largely unclear. In order to gain insights into Tam-mediated antibreast
      cancer actions, we applied 2DE and MS based proteomics approach to identify
      target proteins of Tam. We identified E6-associated protein, i.e. E6AP (UBE3A)
      among others to be regulated by Tam that otherwise is upregulated in breast
      tumors. We confirmed our 2DE finding by immunoblotting and further show that Tam
      leads to inhibition of E6AP expression presumably by promoting its
      autoubiquitination, which is coupled with nuclear export and subsequent
      proteasome-mediated degradation. Furthermore, we show that Tam- and siE6AP
      mediated inhibition of E6AP leads to enhanced G0-G1 growth arrest and apoptosis,
      which is also evident from significant upregulation of cytochrome-c, Bax, p21,
      and PARP cleavage. Taken together, our data suggest that, Tam-targeted E6AP
      inhibition is in fact required for Tam-mediated antibreast cancer actions. Thus,
      E6AP may be a therapeutic target in breast cancer.

PMID- 22589189
TI  - Proteogenomic evidence for beta-oxidation of plant-derived 3-phenylpropanoids in
      "Aromatoleum aromaticum" EbN1.
AB  - The betaproteobacterium "Aromatoleum aromaticum" EbN1 utilizes eight different
      plant-derived nonhydroxylated (e.g. cinnamate) and hydroxylated (e.g. p
      coumarate) 3-phenylpropanoids with nitrate as electron acceptor. Differential
      protein profiling (2D-DIGE) revealed abundance increases of five proteins
      (EbA5316 to EbA5320) during anaerobic growth with cinnamate, hydrocinnamate, p
      coumarate, and 3-(4-hydroxyphenyl)propanoate, compared to anaerobic benzoate
      adapted cells serving as reference state. The predicted functions of four of
      these proteins (EbA5317, fatty acid-coenzyme A (CoA) ligase; EbA5318, enoyl-CoA
      hydratase/isomerase; EbA5319, beta-ketothiolase; and EbA5320, 3-hydroxyacyl-CoA
      dehydrogenase) suggest beta-oxidation of the above 3-phenylpropanoids to benzoyl
      CoA and p-hydroxybenzoyl-CoA, respectively. The fifth protein (EbA5316, ABC-type
      periplasmic solute-binding protein) could be involved in 3-phenylpropanoid
      uptake. The detection of 3-hydroxy-3-phenylpropanoate during anaerobic growth
      with cinnamate and hydrocinnamate or 3-hydroxy-3-(4-hydroxyphenyl)propanoate
      during anaerobic growth with p-coumarate and 3-(4-hydroxyphenyl)propanoate
      supports the proteome-predicted beta-oxidation pathway. Based on the specific
      formation of EbA5316-20 also during anaerobic growth with further 3
      phenylpropanoid growth substrates including cinnamyl alcohol, m-coumarate, 3-(3,4
      dihydroxyphenyl)propanoate and 3,4-dihydroxycinnamate (caffeate), a common beta
      oxidation route is proposed for 3-phenylpropanoid degradation in strain EbN1. The
      low amount of metabolites attributable to cometabolic transformation of nongrowth
      supporting 3-phenylpropanoids (e.g. o-coumarate, ferulate) may be indicative for
      a high substrate specificity of the involved enzymes.

PMID- 22589188
TI  - Dissecting the Escherichia coli periplasmic chaperone network using differential
      proteomics.
AB  - beta-Barrel proteins, or outer membrane proteins (OMPs), perform many essential
      functions in Gram-negative bacteria, but questions remain about the mechanism by
      which they are assembled into the outer membrane (OM). In Escherichia coli, beta
      barrels are escorted across the periplasm by chaperones, most notably SurA and
      Skp. However, the contributions of these two chaperones to the assembly of the OM
      proteome remained unclear. We used differential proteomics to determine how the
      elimination of Skp and SurA affects the assembly of many OMPs. We have shown that
      removal of Skp has no impact on the levels of the 63 identified OM proteins.
      However, depletion of SurA in the skp strain has a marked impact on the OM
      proteome, diminishing the levels of almost all beta-barrel proteins. Our results
      are consistent with a model in which SurA plays a primary chaperone role in E.
      coli. Furthermore, they suggest that while no OMPs prefer the Skp chaperone
      pathway in wild-type cells, most can use Skp efficiently when SurA is absent. Our
      data, which provide a unique glimpse into the protein content of the nonviable
      surA skp mutant, clarify the roles of the periplasmic chaperones in E. coli.

PMID- 22589190
TI  - Close proximity of phosphorylation sites to ligand in the phosphoproteome of the
      extreme thermophile Thermus thermophilus HB8.
AB  - We performed phosphoproteome analysis of proteins from the extremely thermophilic
      Gram-negative eubacterium Thermus thermophilus HB8 using gel-free mass
      spectrometric method. We identified 52 phosphopeptides from 48 proteins and
      determined 46 phosphorylation sites: 30 on serine, 12 on threonine, and 4 on
      tyrosine. The identified phosphoproteins are known to be involved in a wide
      variety of cellular processes. To help elucidate the functional roles of these
      phosphorylation events, we mapped the phosphorylation sites on the known tertiary
      structures of the respective proteins. In all, we succeeded in mapping 46 sites
      (approximately 88%) on the corresponding structures. Most of the phosphorylation
      sites were found to be located on loops and terminal regions of the secondary
      structures. Surprisingly, 28 of these sites were situated at or near the active
      site of the enzyme. In particular, 18 sites were within 4 A of the ligand,
      including substrate or cofactor. Such structural locations suggest direct effects
      of the phosphorylation on the binding of ligand in addition to inducing a
      conformational change. Interestingly, 19 of these 28 phosphorylation sites were
      situated near the phosphate moiety of a substrate or cofactor. In oligomeric
      proteins, 5 phosphorylation sites were found at the subunit interface. Based on
      these results, we propose a regulatory mechanism that involves Ser/Thr/Tyr
      phosphorylation in T. thermophilus HB8.

PMID- 22589191
TI  - Early changes in the liver-soluble proteome from mice fed a nonalcoholic
      steatohepatitis inducing diet.
AB  - Despite the increasing incidence of nonalcoholic steatohepatitis (NASH) with the
      rise in lifestyle-related diseases such as the metabolic syndrome, little is
      known about the changes in the liver proteome that precede the onset of
      inflammation and fibrosis. Here, we investigated early changes in the liver
      soluble proteome of female C57BL/6N mice fed an NASH-inducing diet by 2D-DIGE and
      nano-HPLC-MS/MS. In parallel, histology and measurements of hepatic content of
      triglycerides, cholesterol and intermediates of the methionine cycle were
      performed. Hepatic steatosis manifested itself after 2 days of feeding, albeit
      significant changes in the liver-soluble proteome were not evident before day 10
      in the absence of inflammatory or fibrotic signs. Proteomic alterations affected
      mainly energy and amino acid metabolism, detoxification processes, urea cycle,
      and the one-carbon/S-adenosylmethionine pathways. Additionally, intermediates of
      relevant affected pathways were quantified from liver tissue, confirming the
      findings from the proteomic analysis.

PMID- 22589192
TI  - Comprehensive identification of novel post-translational modifications in
      cellular peroxiredoxin 6.
AB  - Peroxiredoxin 6 (PRDX6), a 1-Cys peroxiredoxin, is a bifunctional enzyme acting
      both as a glutathione peroxidase and a phospholipase A2. However, the underlying
      mechanisms and their regulation mechanisms are not well understood. Because post
      translational modifications (PTMs) have been shown to play important roles in the
      function of many proteins, we undertook, in this study, to identify the PTMs in
      PRDX6 utilizing proteomic tools including nanoUPLC-ESI-q-TOF MS/MS employing
      selectively excluded mass screening analysis (SEMSA) in conjunction with MOD(i) 
      and MODmap algorithm. We chose PRDX6 obtained from liver tissues from two inbred
      mouse strains, C57BL/6J and C3H/HeJ, which vary in their susceptibility to high
      fat diet-induced obesity and atherosclerosis, and a B16F10 melanoma cell line for
      this study. When PRDX6 protein samples were separated on 2D-PAGE based on pI,
      several PRDX6 spots appeared. They were purified and the low abundant PTMs in
      each PRDX6 spot were analyzed. Unexpected mass shifts (Deltam = -34, +25, +64,
      +87, +103, +134, +150, +284 Da) observed at active site cysteine residue (Cys47)
      were quantified using precursor ion intensities. Mass differences of -34, +25,
      and +64 Da are presumed to reflect the conversion of cysteine to dehydroalanine,
      cyano, and Cys-SO(2) -SH, respectively. We also detected acrylamide adducts of
      sulfenic and sulfinic acids (+87 and +103 Da) as well as unknown modifications
      (+134, +150, +284 Da). Comprehensive analysis of these PTMs revealed that the
      PRDX6 exists as a heterogeneous mixture of molecules containing a multitude of
      PTMs. Several of these modifications occur at cysteine residue in the enzyme
      active site. Other modifications observed, in PRDX6 from mouse liver tissues
      included, among others, mono- and dioxidation at Trp and Met, acetylation at Lys,
      and deamidation at Asn and Gln. Comprehensive identification of the diverse PTMs
      occurring in this bifunctional PRDX6 enzyme should help understand how PRDX6
      plays key roles in oxidative stresses.

PMID- 22589193
TI  - Proteomic analysis of the microenvironment of developing oocytes.
AB  - We utilized a setup based on extensive pre-fractionation of proteolytic peptides
      and nanoflow reversed-phase LC-MS/MS to identify the (sub)proteome of human
      follicular fluid (FF). In this in-depth screen, 246 specific proteins were
      identified, the majority of which are involved in coagulation- and immune
      response pathways. Our aim is to define a set of FF protein markers, which could
      predict oocyte quality.

PMID- 22589197
TI  - Sensitivity to lexical stress in dyslexia: a case of cognitive not perceptual
      stress.
AB  - Sensitivity to lexical stress in adult German-speaking students with reading
      difficulty was investigated using minimal pair prepositional verbs whose meaning
      and syntax depend on the location of the stressed syllable. Two tests of stress
      perception were used: (i) a stress location task, where listeners indicated the
      location of the perceptually most prominent syllable, and (ii) a stress pattern
      identification task, where listeners indicated if the stress pattern was
      appropriate for its semantic frame. The students with reading difficulties
      performed worse than the normally reading students on both tasks. Their poorer
      performance did not reflect the lack of a percept for lexical stress rather
      patterns of performance across the two tasks suggested that each loaded onto
      different underlying cognitive abilities. Deficits in these, rather than
      perceptual difficulties, explained observed group differences. Students with
      reading difficulties have a normal implicit knowledge of lexical stress usage but
      lack the necessary cognitive resources for developing an explicit metalinguistic
      awareness of it. Deficits in these skills not deficiencies in lexical stress
      perception are implicated in their reading difficulties.

PMID- 22589198
TI  - Can commonly used hydrazine produce n-type graphene?
AB  - A simple chemical method to obtain bulk quantities of N-doped, reduced graphene
      oxide (rGO) sheets (see figure) as an n-type semiconductor through the treatment
      of as-prepared GO sheets with the commonly used reducing reagent hydrazine,
      followed by rapid thermal annealing (RTA) is described.

PMID- 22589199
TI  - Effect of maturation and cold storage on the organic acid composition of myrtle
      fruits.
AB  - BACKGROUND: The effect of maturation and senescence on the chemical composition
      of two myrtle cultivars was studied in mature, overripe and cold-stored fruits in
      order to find the most appropriate harvesting period and best storage technology
      for industrial purposes. RESULTS: After cold storage at 10  degrees C for 15
      days, berry weight loss ranged from 12.5 to 18.4%, with the highest losses in
      less mature fruits. Titratable acidity decreased during maturation and cold
      storage in both cultivars. Reducing and total sugars increased during maturation.
      Anthocyanin concentration increased during maturation but decreased in overripe
      berries. The major organic acids in myrtle fruits were quinic, malic and gluconic
      acids. In fresh and cold-stored fruits, malic acid rose to 3 g kg(-1) and
      decreased thereafter. Quinic acid peaked at 90 or 120 days after bloom and
      decreased thereafter to reach low concentrations in mature fruits. CONCLUSION:
      Cold storage for 15 days at 10  degrees C does not affect myrtle fruit quality
      for liqueur production. Anthocyanin concentration is the best indicator of
      harvest time for industrial purposes. Gluconic acid concentration is high in
      mature, overripe and cold-stored berries. This parameter can be used as a marker
      of the onset of fruit senescence.

PMID- 22589202
TI  - Role of thiopurine metabolite measurement in the management of autoimmune
      hepatitis.

PMID- 22589201
TI  - Villin promoter-mediated transgenic expression of transient receptor potential
      cation channel, subfamily V, member 6 (TRPV6) increases intestinal calcium
      absorption in wild-type and vitamin D receptor knockout mice.
AB  - Transient receptor potential cation channel, subfamily V, member 6 (TRPV6) is an
      apical membrane calcium (Ca) channel in the small intestine proposed to be
      essential for vitamin D-regulated intestinal Ca absorption. Recent studies have
      challenged the proposed role for TRPV6 in Ca absorption. We directly tested
      intestinal TRPV6 function in Ca and bone metabolism in wild-type (WT) and vitamin
      D receptor knockout (VDRKO) mice. TRPV6 transgenic mice (TG) were made with
      intestinal epithelium-specific expression of a 3X Flag-tagged human TRPV6
      protein. TG and VDRKO mice were crossed to make TG-VDRKO mice. Ca and bone
      metabolism was examined in WT, TG, VDRKO, and TG-VDRKO mice. TG mice developed
      hypercalcemia and soft tissue calcification on a chow diet. In TG mice fed a
      0.25% Ca diet, Ca absorption was more than three-fold higher and femur bone
      mineral density (BMD) was 26% higher than WT. Renal 1alpha hydroxylase (CYP27B1)
      mRNA and intestinal expression of the natural mouse TRPV6 gene were reduced to
      <10% of WT but small intestine calbindin-D(9k)  expression was elevated >15 times
      in TG mice. TG-VDRKO mice had high Ca absorption that prevented the low serum Ca,
      high renal CYP27B1 mRNA, low BMD, and abnormal bone microarchitecture seen in
      VDRKO mice. In addition, small intestinal calbindin D(9K)  mRNA and protein
      levels were elevated in TG-VDRKO. Transgenic TRPV6 expression in intestine is
      sufficient to increase Ca absorption and bone density, even in VDRKO mice. VDR
      independent upregulation of intestinal calbindin D(9k)  in TG-VDRKO suggests this
      protein may buffer intracellular Ca during Ca absorption. (c) 2012 American
      Society for Bone and Mineral Research.

PMID- 22589203
TI  - Hedgehog signalling and LSEC capillarisation: stopping this one in its tracks.

PMID- 22589205
TI  - Unravelling the role of GABAA receptor subtypes in distinct neurons and
      behaviour.

PMID- 22589206
TI  - How does CO2 activate the neurons of the retrotrapezoid nucleus?

PMID- 22589207
TI  - The play is still being written on opening day: postnatal maturation of enteric
      neurons may provide an opening for early life mischief.

PMID- 22589208
TI  - Astroglial glutamate transporters trigger glutaminergic gliotransmission.

PMID- 22589209
TI  - An introduction to a symposium dedicated to the scientific achievements of Roger
      Nicoll.

PMID- 22589210
TI  - Directional coherence disentangles causality within the sensorimotor loop, but
      cannot open the loop.

PMID- 22589212
TI  - The vagus and the heart: revisiting an early contribution to a still on-going
      dispute.

PMID- 22589214
TI  - Circadian expression of the presynaptic active zone protein Bruchpilot in the
      lamina of Drosophila melanogaster.
AB  - In the fly's visual system, the morphology of cells and the number of synapses
      change during the day. In the present study we show that in the first optic
      neuropil (lamina) of Drosophila melanogaster, a presynaptic active zone protein
      Bruchpilot (BRP) exhibits a circadian rhythm in abundance. In day/night (or
      light/dark, LD) conditions the level of BRP increases two times, in the morning
      and in the evening. The same pattern of changes in the BRP level was detected in
      whole brain homogenates, thus indicating that the majority of synapses in the
      brain peaks twice during the day. However, these two peaks in BRP abundance,
      measured as the fluorescence intensity of immunolabeling, seem to be regulated
      differently. The peak in the morning is predominantly regulated by light and
      involves the transduction pathway in the retina photoreceptors. This peak is
      present neither in wild-type Canton-S flies in constant darkness (DD), nor in
      norpA(7) phototransduction mutant in LD. However, it also depends on the clock
      gene per, because it is abolished in the per(0) arrhythmic mutant. In turn, the
      peak of BRP in the evening is endogenously regulated by an input from the
      pacemaker located in the brain. This peak is present in Canton-S flies in DD, as
      well as in the norpA(7) mutant in LD, but is absent in per(01), tim,(01) and
      cry(01) mutants in LD. In addition both peaks seem to depend on clock gene
      expressing photoreceptors and glial cells of the visual system.

PMID- 22589215
TI  - Combining many interaction networks to predict gene function and analyze gene
      lists.
AB  - In this article, we review how interaction networks can be used alone or in
      combination in an automated fashion to provide insight into gene and protein
      function. We describe the concept of a "gene-recommender system" that can be
      applied to any large collection of interaction networks to make predictions about
      gene or protein function based on a query list of proteins that share a function
      of interest. We discuss these systems in general and focus on one specific
      system, GeneMANIA, that has unique features and uses different algorithms from
      the majority of other systems.

PMID- 22589218
TI  - Ionic-liquid-mediated active-site control of MoS2 for the electrocatalytic
      hydrogen evolution reaction.
AB  - The layered crystal MoS(2)  has been proposed as an alternative to noble metals
      as the electrocatalyst for the hydrogen evolution reaction (HER). However, the
      activity of this catalyst is limited by the number of available edge sites. It
      was previously shown that, by using an imidazolium ionic liquid as synthesis
      medium, nanometre-size crystal layers of MoS(2)  can be prepared which exhibit a
      very high number of active edge sites as well as a de-layered morphology, both of
      which contribute to HER electrocatalytic activity. Herein, it is examined how to
      control these features synthetically by using a range of ionic liquids as
      synthesis media. Non-coordinating ILs with a planar heterocyclic cation produced
      MoS(2)  with the de-layered morphology, which was subsequently shown to be highly
      advantageous for HER electrocatalytic activity. The results furthermore suggest
      that the crystallinity, and in turn the catalytic activity, of the MoS(2)  layers
      can be improved by employing an IL with specific solvation properties. These
      results provide the basis for a synthetic strategy for increasing the HER
      electrocatalytic activity of MoS(2)  by tuning its crystal properties, and thus
      improving its potential for use in hydrogen production technologies.

PMID- 22589220
TI  - Are prophylactic antibiotics necessary for otologic surgery?

PMID- 22589222
TI  - The impact of neighborhoods on intimate partner violence and victimization.
AB  - Research on intimate partner violence (IPV) and victimization is widespread
      across disciplines. To date, the majority of research underscores the importance
      of individual-level factors to explain IPV, thereby neglecting the significance
      of macro-level elements. Nevertheless, research suggests that the characteristics
      of the neighborhood where an individual lives are important for fully
      understanding IPV. This review focuses on the effects of neighborhoods and macro
      level context on violence between intimate partners, specifically identifying
      empirical studies that have examined contextual predictors of IPV utilizing the
      major tenets of social disorganization theory. The authors note consistencies and
      differences across research results and describe study features that may
      influence the patterns of these findings. Finally, the authors provide both
      theoretical and methodological recommendations for future research.

PMID- 22589224
TI  - Synaptotagmin-1 promotes the formation of axonal filopodia and branches along the
      developing axons of forebrain neurons.
AB  - Synaptotagmin-1 (syt1) is a Ca(2+)-binding protein that functions in regulation
      of synaptic vesicle exocytosis at the synapse. Syt1 is expressed in many types of
      neurons well before synaptogenesis begins both in vivo and in vitro. To determine
      if expression of syt1 has a functional role in neuronal development before
      synapse formation, we examined the effects of syt1 overexpression and knockdown
      on the growth and branching of the axons of cultured primary embryonic day 8
      chicken forebrain neurons. In vivo these neurons express syt1, and most have not
      yet extended axons. We present evidence that syt1 plays a role in regulating axon
      branching, while not regulating overall axon length. To study the effects of
      overexpression of syt1, we used adenovirus-mediated infection to introduce a syt1
      YFP construct, or control GFP construct, into neurons. Syt1 levels were reduced
      using RNA interference. Overexpression of syt1 increased the formation of axonal
      filopodia and branches. Conversely, knockdown of syt1 decreased the number of
      axonal filopodia and branches. Time-lapse analysis of filopodial dynamics in syt1
      overexpressing cells demonstrated that elevation of syt1 levels increased both
      the frequency of filopodial initiation and their lifespan. Taken together these
      data indicate that syt1 regulates the formation of axonal filopodia and branches
      before engaging in its conventional functions at the synapse.

PMID- 22589225
TI  - Interactome mapping for analysis of complex phenotypes: insights from
      benchmarking binary interaction assays.
AB  - Protein interactions mediate essentially all biological processes and analysis of
      protein-protein interactions using both large-scale and small-scale approaches
      has contributed fundamental insights to the understanding of biological systems.
      In recent years, interactome network maps have emerged as an important tool for
      analyzing and interpreting genetic data of complex phenotypes. Complementary
      experimental approaches to test for binary, direct interactions, and for
      membership in protein complexes are used to explore the interactome. The two
      approaches are not redundant but yield orthogonal perspectives onto the complex
      network of physical interactions by which proteins mediate biological processes.
      In recent years, several publications have demonstrated that interactions from
      high-throughput experiments can be equally reliable as the high quality subset of
      interactions identified in small-scale studies. Critical for this insight was the
      introduction of standardized experimental benchmarking of interaction and
      validation assays using reference sets. The data obtained in these benchmarking
      experiments have resulted in greater appreciation of the limitations and the
      complementary strengths of different assays. Moreover, benchmarking is a central
      element of a conceptual framework to estimate interactome sizes and thereby
      measure progress toward near complete network maps. These estimates have revealed
      that current large-scale data sets, although often of high quality, cover only a
      small fraction of a given interactome. Here, I review the findings of assay
      benchmarking and discuss implications for quality control, and for strategies
      toward obtaining a near-complete map of the interactome of an organism.

PMID- 22589223
TI  - Parathyroid hormone induces differentiation of mesenchymal stromal/stem cells by
      enhancing bone morphogenetic protein signaling.
AB  - Parathyroid hormone (PTH) stimulates bone remodeling and induces differentiation
      of bone marrow mesenchymal stromal/stem cells (MSCs) by orchestrating activities
      of local factors such as bone morphogenetic proteins (BMPs). The activity and
      specificity of different BMP ligands are controlled by various extracellular
      antagonists that prevent binding of BMPs to their receptors. Low-density
      lipoprotein receptor-related protein 6 (LRP6) has been shown to interact with
      both the PTH and BMP extracellular signaling pathways by forming a complex with
      parathyroid hormone 1 receptor (PTH1R) and sharing common antagonists with BMPs.
      We hypothesized that PTH-enhanced differentiation of MSCs into the osteoblast
      lineage through enhancement of BMP signaling occurs by modifying the
      extracellular antagonist network via LRP6. In vitro studies using multiple cell
      lines, including Sca-1(+) CD45(-) CD11b(-) MSCs, showed that a single injection
      of PTH enhanced phosphorylation of Smad1 and could also antagonize the inhibitory
      effect of noggin. PTH treatment induced endocytosis of a PTH1R/LRP6 complex and
      resulted in enhancement of phosphorylation of Smad1 that was abrogated by
      deletion of PTH1R, beta-arrestin, or chlorpromazine. Deletion of LRP6 alone led
      to enhancement of pSmad1 levels that could not be further increased with PTH
      treatment. Finally, knockdown of LRP6 increased the exposure of endogenous cell
      surface BMP receptor type II (BMPRII) significantly in C2C12 cells, and PTH
      treatment significantly enhanced cell-surface binding of (125) I-BMP2 in a dose-
      and time-dependent manner, implying that LRP6 organizes an extracellular network
      of BMP antagonists that prevent access of BMPs to BMP receptors. In vivo studies
      in C57BL/6J mice and of transplanted green fluorescent protein (GFP)-labeled Sca
      1(+) CD45(-) CD11b(-) MSCs into the bone marrow cavity of Rag2(-/-)
      immunodeficient mice showed that PTH enhanced phosphorylation of Smad1 and
      increased commitment of MSCs to osteoblast lineage, respectively. These data
      demonstrate that PTH enhancement of MSC differentiation to the osteoblast lineage
      occurs through a PTH- and LRP6-dependent pathway by endocytosis of the PTH1R/LRp6
      complex, allowing enhancement of BMP signaling.

PMID- 22589227
TI  - Providing mental health care to veterans in rural areas: using telehealth in
      mobile clinics.
AB  - The purpose of this article is to provide information to improve the quality of
      care of veterans living in geographically isolated areas who require treatment
      for mental health issues. Because interactive care solutions are currently hot
      topics in the health care community, they should be viewed as possible strategies
      to meet the needs of this specialty group of veterans. An intervention using a
      mobile clinic and clinical video telehealth reduces distance barriers by making
      it possible for mental health specialists to come to rural veterans instead of
      the veteran attempting to find a way to get to the practitioner, who may be
      located in a clinic or hospital many miles away. This article focuses on an
      alternate strategy-telehealth in mobile clinics-as a possible solution to the
      mental health crisis of veterans in rural areas.

PMID- 22589226
TI  - Willingness-to-pay for a rapid malaria diagnostic test and artemisinin-based
      combination therapy from private drug shops in Mukono District, Uganda.
AB  - In Uganda, as in many parts of Africa, the majority of the population seek
      treatment for malaria in drug shops as their first point of care; however,
      parasitological diagnosis is not usually offered in these outlets. Rapid
      diagnostic tests (RDTs) for malaria have attracted interest in recent years as a
      tool to improve malaria diagnosis, since they have proved accurate and easy to
      perform with minimal training. Although RDTs could feasibly be performed by drug
      shop vendors, it is not known how much customers would be willing to pay for an
      RDT if offered in these settings. We conducted a contingent valuation survey
      among drug shop customers in Mukono District, Uganda. Exit interviews were
      undertaken with customers aged 15 years and above after leaving a drug shop
      having purchased an antimalarial and/or paracetamol. The bidding game technique
      was used to elicit the willingness-to-pay (WTP) for an RDT and a course of
      artemisinin-based combination therapy (ACT) with and without RDT confirmation.
      Factors associated with WTP were investigated using linear regression. The
      geometric mean WTP for an RDT was US$0.53, US$1.82 for a course of ACT and
      US$2.05 for a course of ACT after a positive RDT. Factors strongly associated
      with a higher WTP for these commodities included having a higher socio-economic
      status, no fever/malaria in the household in the past 2 weeks and if a malaria
      diagnosis had been obtained from a qualified health worker prior to visiting the
      drug shop. The findings further suggest that the WTP for an RDT and a course of
      ACT among drug shop customers is considerably lower than prevailing and estimated
      end-user prices for these commodities. Increasing the uptake of ACTs in drug
      shops and restricting the sale of ACTs to parasitologically confirmed malaria
      will therefore require additional measures.

PMID- 22589228
TI  - Neuropsychology and cognitive health in healthy older adults: a brief overview
      for psychiatric nurses.
AB  - This article contains a brief synopsis on nonpathological aspects of the
      neuropsychology of aging and cognitive health. In nonpathological aging, normal
      subtle decline occurs in a number of cognitive domains such as executive
      functioning, speed of processing, memory, language, and psychomotor ability;
      however, some domains of cognitive functioning appear to increase with age, such
      as vocabulary and crystallized intelligence. In the neuropsychology and the
      cognitive aging literatures, several hypotheses for such age-related declines are
      proposed, including the diminished speed-of-processing hypothesis, the common
      cause hypothesis, and the frontal aging hypothesis. As these age-related changes
      diminish cognitive reserve, the decline in the related cognitive domains emerges.
      Ways to protect and improve cognitive health are suggested to encourage positive
      neuroplasticity and discourage negative neuroplasticity. Implications for nursing
      practice are provided.

PMID- 22589229
TI  - Screening for pediatric bipolar disorder in primary care.
AB  - A child or adolescent with pediatric bipolar disorder (PBD) is at higher risk for
      suicide, violence, and impaired psychosocial functioning. The prevalence of
      diagnosed PBD has increased 40-fold in less than 2 decades, leading some to
      believe that PBD is inaccurately diagnosed. Complicating this issue,
      disagreements exist among clinicians as to the utility of current screening
      methods. The assessment picture is further muddied by the high rate of comorbid
      psychiatric conditions. A literature review was performed to describe the present
      understanding of PBD and identify current practices of screening for the
      disorder. Although screening tools are available, the literature suggests they
      lack validity. Awareness, a thorough interview, and expedient referral may assist
      clinicians in making a correct diagnosis. Accurate assessment will help ease the
      psychological and economic burden of PBD.

PMID- 22589230
TI  - Dietary supplement drug therapies for depression.
AB  - Many dietary supplements are readily accessible and commonly used for the
      treatment of depression. A dietary supplement is a product intended to supplement
      the diet but is not intended to treat, diagnose, prevent, or cure disease. The
      U.S. Food and Drug Administration can take action against dietary supplement
      manufacturers for products only after they are marketed, mainly if the product is
      found to be unsafe or if false or misleading claims are made about the product.
      Few dietary supplement products have been adequately studied for their safety and
      efficacy. Of the five products reviewed in this article (L-methylfolate, S
      adenosyl-L-methionine [SAM-e], omega-3 fatty acids, L-tryptophan, and inositol),
      only omega-3 fatty acids and SAM-e have sufficient supporting evidence for their
      efficacy to warrant safe use.

PMID- 22589231
TI  - Synthesis of an enlarged library of dynamic DNA activators with oxime, disulfide
      and hydrazone bridges.
AB  - Dynamic amphiphiles have a "bridge" between their charged head and their
      hydrophobic tails. The presence of dynamic covalent bonds is of interest for
      differential and biosensing applications as well as for rapid access to the
      libraries needed to screen for gene delivery or cellular uptake of siRNA.
      However, efforts to develop libraries have so far concentrated on hydrazone
      bridges to monocationic heads. Here, we report synthesis efforts to enlarge this
      focused library with oxime and disulfide bridges and dynamic amphiphiles with
      more than one positive charge. Evaluation in fluorogenic vesicles reveals best
      activation of DNA as ion transporters by dynamic amphiphiles with dendritic
      scaffolds, doubly charged heads and four tails. Moreover, oximes, contrary to
      hydrazones, remain active under acidic conditions. Linear elongation of dendritic
      head-groups seems to cause increasing detergent effects and should therefore be
      avoided.

PMID- 22589232
TI  - Beneficial effect of hydrogen-rich saline on cerebral vasospasm after
      experimental subarachnoid hemorrhage in rats.
AB  - Cerebral vasospasm (CV) remains a common and devastating complication in patients
      with subarachnoid hemorrhage (SAH). Despite its clinical significance and
      extensive research, the underlying pathogenesis and therapeutic perspectives of
      CV remain incompletely understood. Recently, it has been suggested that molecular
      hydrogen (H(2)) can selectively reduce levels of hydroxyl radicals (.OH) and
      ameliorate oxidative and inflammatory injuries to organs in many models. However,
      whether H(2) can ameliorate CV after SAH is still unknown. This study was
      designed to evaluate the efficacy of H(2) in preventing SAH-induced CV.
      Experimental SAH was induced in Sprague-Dawley rats using cisterna magna blood
      injection. Hydrogen-rich saline (HS) was injected intraperitoneally (5 ml/kg)
      immediately and at 24 hr after injury. All rats were sacrificed 48 hr after the
      neurological examination scores had been recorded following SAH. Levels of
      oxidative stress and inflammation were evaluated. Basilar artery vasospasm was
      assessed by histological examination using light and transmission electron
      microscopy. HS treatment significantly improved neurological outcomes and
      attenuated morphological vasospasm of the basilar artery after SAH. In addition,
      we found that the beneficial effects of HS treatment on SAH-induced CV were
      associated with decreased levels of lipid peroxidation, increased activity of
      antioxidant enzymes, and reduced levels of proinflammatory cytokines in the
      basilar artery. These results indicate that H(2) has the potential to be a novel
      therapeutic strategy for the treatment of CV after SAH, and its neuroprotective
      effect might be partially mediated via limitation of vascular inflammation and
      oxidative stress.

PMID- 22589233
TI  - Concentrations of atomoxetine and its metabolites in plasma and oral fluid from
      paediatric patients with attention deficit/hyperactivity disorder.
AB  - Atomoxetine (ATX) is a non-stimulant drug approved for the treatment of children
      and adolescents with attention deficit/hyperactivity disorder (ADHD). We aimed to
      study the excretion profile of ATX and its principal metabolites 4
      hydroxyatomoxetine (4-OH-ATX) and N-desmethylatomoxetine (desmethyl-ATX) in oral
      fluid and plasma of ADHD paediatric subjects, after administration of different
      dosage regimens. Oral fluid and plasma samples were obtained from one child and
      five adolescents treated with different ATX doses (18-60 mg/day). ATX and its
      metabolites were measured in oral fluid and plasma by liquid chromatography-mass
      spectrometry (LC-MS). Apparent pharmacokinetic parameters of ATX in oral fluid
      and plasma were estimated for each subject. All analytes under investigation were
      detected in plasma samples with concentrations from 0.6 to 1065.7 ng/ml for ATX,
      0.7 to 17.1 ng/ml for 4-OH-ATX and 0.7 to 126.2 ng/ml for desmethyl-ATX. Only ATX
      and 4-OH-ATX were detected in oral fluid samples with concentrations from 0.5 to
      36.0 ng/ml and 0.5 to 4.7 ng/ml, respectively. ATX concentrations in oral fluid
      were between one and two orders of magnitude lower than those in plasma. 4-OH-ATX
      was found in oral fluid at a peak concentration approximately one-fourth those in
      plasma with a mean tmax of 2.3 in plasma and 3.0 h in oral fluid. The
      correlations between ATX and 4-OH-ATX concentrations in the two biological fluids
      indicate that oral fluid concentrations of this drug and its principal metabolite
      may be a predictor of plasma concentrations, even if values are too low and
      variable to be considered an alternative to plasma.

PMID- 22589234
TI  - Mediators of induced pluripotency and their role in cancer cells - current
      scientific knowledge and future perspectives.
AB  - The discovery that overexpression of the transcription factors Oct4, Sox2, Klf4
      and c-Myc reprograms differentiated cells into "induced pluripotent stem cells"
      (iPSCs) has extended our understanding of mechanisms required to maintain stem
      cell pluripotency and to drive differentiation. Subsequently, additional factors
      have been discovered that are able to induce a pluripotent state. Recently
      several groups have succeeded in reprogramming cancer cells to iPSC-like induced
      pluripotent cancer cells by use of the method established for the generation of
      iPSCs. This discovery highlighted several striking similarities between
      pluripotent stem cells and cancer cells, in turn implying that tumorigenesis and
      reprogramming are partly promoted by overlapping mechanisms. Thus, research on
      reprogramming might help unravel the mechanisms of carcinogenesis, and vice
      versa. This review gives an overview of the common features of pluripotent stem
      cells and cancer cells and summarizes the present state of knowledge in the field
      of cancer cell reprogramming.

PMID- 22589235
TI  - Tetrakis(phthalocyaninato) rare-earth-cadmium-rare-earth quadruple-decker
      sandwich SMMs: suppression of QTM by long-distance f-f interactions.
AB  - Long-distance f-f interactions: Systematic and comparative studies of the
      magnetic properties of a series of isostructural sandwich-type
      tetrakis(phthalocyaninato) diterbium and monoterbium quadruple-decker complexes
      clearly reveal the suppression of the quantum tunneling of magnetization by the
      long-distance intramolecular f-f interactions (see figure).

PMID- 22589236
TI  - Assay of therapeutic ultrasound induced-antinociception in experimental
      trigeminal neuropathic pain.
AB  - Trigeminal neuralgia is considered one of the most painful conditions, and
      pharmacological treatment can be as debilitating as the pathology itself. The aim
      of this work was to evaluate the effectiveness of pulsed therapeutic ultrasound
      (TU) on an experimental rat model of trigeminal neuropathic nociception (chronic
      constriction injury-infraorbital nerve; CCI-ION). To evaluate facial
      thermonociception, an apparatus that measured the reaction time for head
      withdrawal was constructed. After surgery, a gradual reduction in reaction time
      was observed until day 15 post-CCI, when the values became constant. Three
      ipsilateral applications of TU to post-CCI rats promoted an increase in latency
      time. This antinociceptive effect was evident even after the first TU
      application, reaching maximal values at 24 hr. The magnitude of this effect was
      proportional to ultrasonic wave intensity (0.3 and 0.4 W/cm(2)). Posttreatment
      with naltrexone (5 mg/kg, s.c.) completely blocked the hypoalgesic effect of TU.
      Pretreatment with an opioid antagonist was unable to block the antinociceptive
      effect during the first 8 hr, suggesting that opioids are involved only in the
      latter phase of the TU effects. Myeloperoxidase (MPO) levels in the infraorbital
      nerve were not increased by TU use, indicating that TU causes no injury or is at
      least insufficient to induce neutrophil migration. In conclusion, TU is an
      effective resource in a model of trigeminal neuropathic pain, with a mechanism
      involving opioid receptor activation, confirming its potential usefulness in the
      treatment of trigeminal neuralgia.

PMID- 22589238
TI  - Valine but not leucine or isoleucine supports neurotransmitter glutamate
      synthesis during synaptic activity in cultured cerebellar neurons.
AB  - Synthesis of neuronal glutamate from alpha-ketoglutarate for neurotransmission
      necessitates an amino group nitrogen donor; however, it is not clear which amino
      acid(s) serves this role. Thus, the ability of the three branched-chain amino
      acids (BCAAs), leucine, isoleucine, and valine, to act as amino group nitrogen
      donors for synthesis of vesicular neurotransmitter glutamate was investigated in
      cultured mouse cerebellar (primarily glutamatergic) neurons. The cultures were
      superfused in the presence of (15) N-labeled BCAAs, and synaptic activity was
      induced by pulses of N-methyl-D-aspartate (300 MUM), which results in release of
      vesicular glutamate. At the end of the superfusion experiment, the vesicular pool
      of glutamate was released by treatment with alpha-latrotoxin (3 nM, 5 min). This
      experimental paradigm allows a separate analysis of the cytoplasmic and vesicular
      pools of glutamate. Amount and extent of (15) N labeling of intracellular amino
      acids plus vesicular glutamate were analyzed employing HPLC and LC-MS analysis.
      Only when [(15) N]valine served as precursor did the labeling of both cytoplasmic
      and vesicular glutamate increase after synaptic activity. In addition, only [(15)
      N]valine was able to maintain the amount of vesicular glutamate during synaptic
      activity. This indicates that, among the BCAAs, only valine supports the
      increased need for synthesis of vesicular glutamate.

PMID- 22589237
TI  - Metformin in obesity, cancer and aging: addressing controversies.
AB  - Metformin, an oral anti-diabetic drug, is being considered increasingly for
      treatment and prevention of cancer, obesity as well as for the extension of
      healthy lifespan. Gradually accumulating discrepancies about its effect on cancer
      and obesity can be explained by the shortage of randomized clinical trials,
      differences between control groups (reference points), gender- and age-associated
      effects and pharmacogenetic factors. Studies of the potential antiaging effects
      of antidiabetic biguanides, such as metformin, are still experimental for obvious
      reasons and their results are currently ambiguous. Here we discuss whether the
      discrepancies in different studies are merely methodological or inherently
      related to individual differences in responsiveness to the drug.

PMID- 22589239
TI  - Technical advances with newer aortic endografts provide additional support to
      withhold the early endovascular repair of small abdominal aortic aneurysms until
      it is really needed.
AB  - The idea of early endovascular aortic repair (EVAR) of "small" abdominal aortic
      aneurysms (AAAs) has gained attention over "watchful waiting," mostly due to the
      concern for losing the anatomic suitability for endovascular repair over time.
      Generally, small AAAs have longer, smaller, less angulated necks, and less
      tortuous iliac arteries than larger ones. Though the borderline anatomic
      characteristics were assumed to be contraindications for older generation
      endografts, the modifications of modern devices seem promising to overcome those
      limitations, in order to treat the small AAAs when reaching the 5.5 cm threshold.
      Moreover, early endovascular intervention has been proven neither cost effective
      nor beneficial for the patients' quality of life. This article evaluates the
      technical progress that could overcome the difficulties of those small AAAs that
      present technically demanding anatomies, thus advocating endovascular
      intervention when they reach the diameter threshold.

PMID- 22589240
TI  - Efficacy of VBHOM to predict outcome following major lower limb amputation.
AB  - PURPOSE: This study tests an existing Vascular Biochemistry and Haematology
      Outcome Model (VBHOM) on independent data and presents further refinements to the
      model. METHODS: Data from 306 patients who underwent lower limb amputation over a
      4-year period were collated. Urea, creatinine, sodium, potassium, hemoglobin,
      white cell count, albumin, age, gender, mode-of-admission, and short-term
      mortality events were extracted from the database. This study tests an existing
      model and trains a new model for predicting mortality using forward stepwise
      logistic regression. RESULTS: The existing model suggests a significant lack of
      fit (c-index = 0.665, P = .04). For the exception of gender and mode-of
      admission, all predictor variables had significant univariate associations with
      short-term mortality (P < .05). The refined model included age, sodium,
      potassium, creatinine, and albumin and had good discriminatory power (c-index =
      0.8, no evidence of lack of fit, P = .616). CONCLUSIONS: Our simplified model had
      good predictive ability and suggests redundancy in input variables used by the
      existing models.

PMID- 22589241
TI  - Endovascular aneurysm management of a gastroduodenal artery aneurysm in a
      multipara pregnant woman.
AB  - The authors describe a case of an intrapancreatic gastroduodenal artery aneurysm
      in a pregnant woman. Successful endovascular therapy was performed for the first
      time in a visceral artery aneurysm during pregnancy as a bailout solution. The
      attributive risk to the fetus from scattered radiation during endovascular
      treatment did not exceed a critical level.

PMID- 22589242
TI  - Stimulus specificity of a steady-state visual-evoked potential-based brain
      computer interface.
AB  - The mechanisms of neural excitation and inhibition when given a visual stimulus
      are well studied. It has been established that changing stimulus specificity such
      as luminance contrast or spatial frequency can alter the neuronal activity and
      thus modulate the visual-evoked response. In this paper, we study the effect that
      stimulus specificity has on the classification performance of a steady-state
      visual-evoked potential-based brain-computer interface (SSVEP-BCI). For example,
      we investigate how closely two visual stimuli can be placed before they compete
      for neural representation in the cortex and thus influence BCI classification
      accuracy. We characterize stimulus specificity using the four stimulus parameters
      commonly encountered in SSVEP-BCI design: temporal frequency, spatial size,
      number of simultaneously displayed stimuli and their spatial proximity. By
      varying these quantities and measuring the SSVEP-BCI classification accuracy, we
      are able to determine the parameters that provide optimal performance. Our
      results show that superior SSVEP-BCI accuracy is attained when stimuli are placed
      spatially more than 5 degrees  apart, with size that subtends at least 2 degrees 
      of visual angle, when using a tagging frequency of between high alpha and beta
      band. These findings may assist in deciding the stimulus parameters for optimal
      SSVEP-BCI design.

PMID- 22589243
TI  - Association of E-selectin gene polymorphisms with ischemic stroke in a Chinese
      Han population.
AB  - The E-selectin gene, a member of the selectin superfamily of adhesion molecules,
      plays an important role in the pathogenesis of thrombovascular diseases. The
      present study was designed to investigate the potential relationship between E
      selectin gene polymorphisms and ischemic stroke in a Chinese Han population.
      Three hundred fourteen ischemic stroke patients and 389 unrelated healthy
      controls were recruited for the study. Three single-nucleotide polymorphisms
      (SNPs)-rs1805193(G98T), rs5361(A561C), and rs5355(C1839T)-in the exon region of
      the E-selectin gene, were genotyped using a Multiplex SNaPshot sequencing assay.
      The data showed that the genotype and allele frequencies of G98T and C1839T SNP
      were similar in both ischemic stroke patients and the controls. In contrast, the
      frequency of both the AC genotype and the C allele of A561C was significantly
      higher in ischemic stroke patients than in healthy controls (P = 0.001, P <
      0.001, respectively). After adjusting for other risk factors (such as
      hypertension, diabetes, tobacco smoking, and alcohol consumption), the E-selectin
      gene AC genotype and C allele of A561C were still associated with a risk of
      ischemic stroke (odds ratio [OR] = 2.73, 95% confidence interval (CI): 1.29-5.76,
      P = 0.008; OR = 2.80, 95% CI: 1.58-4.94, P < 0.001, respectively). Our current
      study demonstrates that the E-selectin SNP A561C is associated with increased
      risk for the development of ischemic stroke in this subset of the Han Chinese
      population.

PMID- 22589244
TI  - Quantum critical phase and Lifshitz transition in an extended periodic Anderson
      model.
AB  - We study the quantum phase transition in f-electron systems as a quantum Lifshitz
      transition driven by selective-Mott localization in a realistic extended Anderson
      lattice model. Using dynamical mean-field theory (DMFT), we find that a quantum
      critical phase with anomalous omega/T scaling separates a heavy Landau-Fermi
      liquid from ordered phase(s). This non-Fermi liquid state arises from a lattice
      orthogonality catastrophe originating  from orbital-selective Mott localization.
      Fermi surface reconstruction occurs via the interplay between and penetration of
      the Green function zeros to the poles, leading to violation of Luttinger's
      theorem in the strange metal. We show how this naturally leads to scale-invariant
      responses in transport. Thus, our work represents a specific DMFT realization of
      the hidden-FL and FL* theories, and holds promise for the study of 'strange'
      metal phases in quantum matter.

PMID- 22589245
TI  - Variable phenotype of del45-55 Becker patients correlated with nNOSMU
      mislocalization and RYR1 hypernitrosylation.
AB  - Duchenne and Becker muscular dystrophies (DMD and BMD) are muscle-wasting
      diseases caused by mutations in the DMD gene-encoding dystrophin. Usually, out-of
      frame deletions give rise to DMD, whereas in-frame deletions result in BMD. BMD
      patients exhibit a less severe disease because an abnormal but functional
      dystrophin is produced. This is the rationale for attempts to correct the reading
      frame by using an exon-skipping strategy. In order to apply this approach to a
      larger number of patients, a multi-exon skipping strategy of exons 45-55 has been
      proposed, because it should correct the mRNA reading frame in almost 75% of DMD
      patients with a deletion. The resulting dystrophin lacks part of the binding site
      for the neuronal nitric oxide synthase (nNOSMU), which normally binds to spectrin
      like repeats 16 and 17 of the dystrophin. Since these domains are encoded by
      exons 42-45, we investigated the nNOSMU status in muscle biopsies from 12 BMD
      patients carrying spontaneous deletions spaning exons 45-55. We found a wide
      spectrum of nNOSMU expression and localization. The strictly cytosolic
      mislocalization of nNOSMU was associated with the more severe phenotypes.
      Cytosolic NO production correlated with both hypernitrosylation of the
      sarcoplasmic reticulum calcium-release-channel ryanodine receptor type-1 (RyR1)
      and release of calstabin-1, a central hub of Ca(2+) signaling and contraction in
      muscle. Finally, this study shows that the terminal truncation of the nNOS
      binding domain in the 'therapeutic' del45-55 dystrophin is not innocuous, since
      it can perturb the nNOS-dependent stability of the RyR1/calstabin-1 complex.

PMID- 22589246
TI  - A greatly extended PPARGC1A genomic locus encodes several new brain-specific
      isoforms and influences Huntington disease age of onset.
AB  - PGC-1alpha has been implicated in the pathogenesis of neurodegenerative
      disorders. Several single-nucleotide polymorphisms (SNPs) located in two separate
      haplotype blocks of PPARGC1A have shown associations with Huntington's disease
      (HD) and Parkinson's disease, but causative SNPs have not been identified. One
      SNP (rs7665116) was located in a highly conserved 233 bp region of intron 2. To
      determine whether rs7665116 is located in an alternative exon, we performed 5'
      RLM-RACE from exon 3 and discovered multiple new transcripts that initiated from
      a common novel promoter located 587 kb upstream of exon 2, but did not contain
      the conserved region harboring rs7665116. Using real-time polymerase chain
      reaction, RNase protection assays and northern blotting, we show that the
      majority of these transcripts are brain specific and are at least equally or
      perhaps more abundant than the reference sequence PPARGC1A transcripts in whole
      brain. Two main transcripts containing independent methionine start codons encode
      full-length brain-specific PGC-1alpha proteins that differ only at their N
      termini (NTs) from PGC-1alpha, encoded by the reference sequence. Additional
      truncated isoforms containing these NTs that are similar to NT-PGC-1alpha exist.
      Other transcripts may encode potential dominant negative forms, as they are
      predicted to lack the second LXXLL motif that serves as an interaction site for
      several nuclear receptors. Furthermore, we show that the new promoter is active
      in neuronal cell lines and describe haplotypes encompassing this region that are
      associated with HD age of onset. The discovery of such a large PPARGC1A genomic
      locus and multiple isoforms in brain warrants further functional studies and may
      provide new tissue-specific targets for treating neurodegenerative diseases.

PMID- 22589247
TI  - Deep sequencing unearths nuclear mitochondrial sequences under Leber's hereditary
      optic neuropathy-associated false heteroplasmic mitochondrial DNA variants.
AB  - Leber's hereditary optic neuropathy (LHON) is associated with mitochondrial DNA
      (mtDNA) ND mutations that are mostly homoplasmic. However, these mutations are
      not sufficient to explain the peculiar features of penetrance and the tissue
      specific expression of the disease and are believed to be causative in
      association with unknown environmental or other genetic factors. Discerning
      between clear-cut pathogenetic variants, such as those that appear to be
      heteroplasmic, and less penetrant variants, such as the homoplasmic, remains a
      challenging issue that we have addressed here using next-generation sequencing
      approach. We set up a protocol to quantify MTND5 heteroplasmy levels in a family
      in which the proband manifests a LHON phenotype. Furthermore, to study this mtDNA
      haplotype, we applied the cybridization protocol. The results demonstrate that
      the mutations are mostly homoplasmic, whereas the suspected heteroplasmic feature
      of the observed mutations is due to the co-amplification of Nuclear mitochondrial
      Sequences.

PMID- 22589248
TI  - Cardiopulmonary dysfunction in the Osteogenesis imperfecta mouse model Aga2 and
      human patients are caused by bone-independent mechanisms.
AB  - Osteogenesis imperfecta (OI) is an inherited connective tissue disorder with
      skeletal dysplasia of varying severity, predominantly caused by mutations in the
      collagen I genes (COL1A1/COL1A2). Extraskeletal findings such as cardiac and
      pulmonary complications are generally considered to be significant secondary
      features. Aga2, a murine model for human OI, was systemically analyzed in the
      German Mouse Clinic by means of in vivo and in vitro examinations of the
      cardiopulmonary system, to identify novel mechanisms accounting for perinatal
      lethality. Pulmonary and, especially, cardiac fibroblast of perinatal lethal
      Aga2/+ animals display a strong down-regulation of Col1a1 transcripts in vivo and
      in vitro, resulting in a loss of extracellular matrix integrity. In addition,
      dysregulated gene expression of Nppa, different types of collagen and Agt in
      heart and lung tissue support a bone-independent vicious cycle of heart
      dysfunction, including hypertrophy, loss of myocardial matrix integrity,
      pulmonary hypertension, pneumonia and hypoxia leading to death in Aga2. These
      murine findings are corroborated by a pediatric OI cohort study, displaying
      significant progressive decline in pulmonary function and restrictive pulmonary
      disease independent of scoliosis. Most participants show mild cardiac valvular
      regurgitation, independent of pulmonary and skeletal findings. Data obtained from
      human OI patients and the mouse model Aga2 provide novel evidence for primary
      effects of type I collagen mutations on the heart and lung. The findings will
      have potential benefits of anticipatory clinical exams and early intervention in
      OI patients.

PMID- 22589249
TI  - Transducer of regulated CREB-binding proteins (TORCs) transcription and function
      is impaired in Huntington's disease.
AB  - Huntington's disease (HD) is an incurable neurological disorder caused by an
      abnormal glutamine repeat expansion in the huntingtin (Htt) protein. In the
      present studies, we investigated the role of Transducers of Regulated cAMP
      response element-binding (CREB) protein activity (TORCs) in HD, since TORCs play
      an important role in the expression of the transcriptional co-regulator
      peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha),
      whose expression is impaired in HD. We found significantly decreased TORC1
      expression levels in STHdhQ111 cells expressing mutant Htt, in the striatum of
      NLS-N171-82Q, R6/2 and HdhQ111 HD transgenic mice and in postmortem striatal
      tissue from HD patients. TORC1 overexpression in wild-type (WT) and Htt striatal
      cells increased CREB mRNA and protein levels, PGC-1alpha promoter activity, mRNA
      expression of the PGC-1alpha, NRF-1, Tfam and CytC genes, mitochondrial DNA
      content, mitochondrial activity and mitochondrial membrane potential. TORC1
      overexpression also increased the resistance of striatal cells to 3
      nitropropionic (3-NP) acid-mediated toxicity. In cultured WT and mutant Htt
      striatal cells, small hairpin RNA-mediated TORC1 knockdown resulted in decreased
      PGC-1alpha expression and increased susceptibility to 3-NP-induced toxicity.
      Overexpression of PGC-1alpha partially prevented TORC1 knockdown-mediated
      increased susceptibility of Htt striatal cells to 3-NP. Specific knockdown of
      TORC1 in the striatum of NLS-N171-82Q HD transgenic mice induced
      neurodegeneration. Lastly, knockdown of Htt prevents transcriptional repression
      of TORC1 and CREB in Htt striatal cells. These findings show that impaired
      expression and function of TORC1, which results in a reduction in PGC-1alpha,
      plays an important role in mitochondrial dysfunction in HD.

PMID- 22589250
TI  - A rat model for LGI1-related epilepsies.
AB  - Mutations of the leucine-rich glioma-inactivated 1 (LGI1) gene cause an autosomal
      dominant partial epilepsy with auditory features also known as autosomal-dominant
      lateral temporal lobe epilepsy. LGI1 is also the main antigen present in sera and
      cerebrospinal fluids of patients with limbic encephalitis and seizures,
      highlighting its importance in a spectrum of epileptic disorders. LGI1 encodes a
      neuronal secreted protein, whose brain function is still poorly understood. Here,
      we generated, by ENU (N-ethyl-N-nitrosourea) mutagenesis, Lgi1-mutant rats
      carrying a missense mutation (L385R). We found that the L385R mutation prevents
      the secretion of Lgi1 protein by COS7 transfected cells. However, the L385R-Lgi1
      protein was found at low levels in the brains and cultured neurons of Lgi1-mutant
      rats, suggesting that mutant protein may be destabilized in vivo. Studies on the
      behavioral phenotype and intracranial electroencephalographic signals from Lgi1
      mutant rats recalled several features of the human genetic disorder. We show that
      homozygous Lgi1-mutant rats (Lgi1(L385R/L385R)) generated early-onset spontaneous
      epileptic seizures from P10 and died prematurely. Heterozygous Lgi1-mutant rats
      (Lgi1(+/L385R)) were more susceptible to sound-induced, generalized tonic-clonic
      seizures than control rats. Audiogenic seizures were suppressed by antiepileptic
      drugs such as carbamazepine, phenytoin and levetiracetam, which are commonly used
      to treat partial seizures, but not by the prototypic absence seizure drug,
      ethosuximide. Our findings provide the first rat model with a missense mutation
      in Lgi1 gene, an original model complementary to knockout mice. This study
      revealed that LGI1 disease-causing missense mutations might cause a depletion of
      the protein in neurons, and not only a failure of Lgi1 secretion.

PMID- 22589252
TI  - Late-onset spondyloarthritis: subset that should not be forgotten.

PMID- 22589251
TI  - Alterations of social interaction through genetic and environmental manipulation
      of the 22q11.2 gene Sept5 in the mouse brain.
AB  - Social behavior dysfunction is a symptomatic element of schizophrenia and autism
      spectrum disorder (ASD). Although altered activities in numerous brain regions
      are associated with defective social cognition and perception, the causative
      relationship between these altered activities and social cognition and perception
      and their genetic underpinnings-are not known in humans. To address these issues,
      we took advantage of the link between hemizygous deletion of human chromosome
      22q11.2 and high rates of social behavior dysfunction, schizophrenia and ASD. We
      genetically manipulated Sept5, a 22q11.2 gene, and evaluated its role in social
      interaction in mice. Sept5 deficiency, against a high degree of homogeneity in a
      congenic genetic background, selectively impaired active affiliative social
      interaction in mice. Conversely, virally guided overexpression of Sept5 in the
      hippocampus or, to a lesser extent, the amygdala elevated levels of active
      affiliative social interaction in C57BL/6J mice. Congenic knockout mice and mice
      overexpressing Sept5 in the hippocampus or amygdala were indistinguishable from
      control mice in novelty and olfactory responses, anxiety or motor activity.
      Moreover, post-weaning individual housing, an environmental condition designed to
      reduce stress in male mice, selectively raised levels of Sept5 protein in the
      amygdala and increased active affiliative social interaction in C57BL/6J mice.
      These findings identify this 22q11.2 gene in the hippocampus and amygdala as a
      determinant of social interaction and suggest that defective social interaction
      seen in 22q11.2-associated schizophrenia and ASD can be genetically and
      environmentally modified by altering this 22q11.2 gene.

PMID- 22589253
TI  - Autofeedback from ultrasound images provides rapid improvement in palpation
      skills for identifying joint swelling in rheumatoid arthritis.
AB  - OBJECTIVE: Joint swelling, an important factor in the classification criteria and
      disease activity assessment in rheumatoid arthritis (RA), renders joint palpation
      a necessary skill for physicians. Ultrasound (US) examination that visualizes
      soft tissue abnormalities is now used to assess musculoskeletal disease. We
      assessed the usefulness of US assessments in enhancing physical joint examination
      skills. METHODS: We examined 1944 joints (bilateral shoulder, elbow, wrist,
      metacarpophalangeal joints 1-5, and knee joints) in 108 patients with RA during
      April-July 2011. We first physically examined and confirmed joint swelling;
      subsequently, the same rheumatologist conducted US examinations and multiple
      assessors graded the joint swelling. When the 2 results differed, we received
      autofeedback from the US results to improve the physical examination skills.
      RESULTS: The sensitivities and specificities of physical examination for US
      detected swollen joint, the correlation coefficient (CC) of the swollen joint
      counts, and the concordance rate in each patient for joint swelling sites and
      power Doppler (PD)-positive sites with the kappa coefficients between the
      physical and US examinations were compared over time. We found that the
      sensitivity of physical examination increased by 42 percentage points (pp), while
      the specificity decreased by 18 pp. The average CC in June-July was greater than
      that in April-May. The percentage of kappa coefficients > 0.8 increased from 8.8%
      to 17% for joint swelling and from 8.3% to 14% for PD-positive sites. CONCLUSION:
      Our results suggest that autofeedback from US assessment provides quick
      improvement in palpation skills for identifying joint swelling in patients with
      RA.

PMID- 22589254
TI  - Safety and efficacy of etanercept in a cohort of patients with juvenile
      idiopathic arthritis under 4 years of age.
AB  - OBJECTIVE: To evaluate safety, tolerability, and efficacy of etanercept in a
      cohort of patients with juvenile idiopathic arthritis (JIA) under 4 years of age.
      METHODS: Data were collected at every visit during treatment with etanercept in
      25 children who began treatment at a mean age of 3 years (range 18-48 months).
      Safety endpoints included the incidence of any adverse events. Efficacy endpoints
      included the American College of Rheumatology (ACR) Pediatric 30, 50, and 70
      criteria for improvement. RESULTS: Data from 25 patients with JIA treated with
      etanercept for a mean period of 23 months were analyzed. All patients received
      concomitant medications: 24 methotrexate, 3 cyclosporin A, and 10
      corticosteroids. After the first 6 months of treatment, 15 (71.4%) patients
      achieved an ACR Pedi30 response and at the last observation 20 (80%) achieved ACR
      Pedi30. ACR Pedi50 and 70 responses were, respectively, 62% and 43% at 6 months
      and 72% and 64% at the last followup. Five patients (20%) discontinued etanercept
      for lack of efficacy. Two (8%) developed adverse events, both primary varicella
      zoster virus (VZV) infections (both not vaccinated). One was hospitalized because
      of a necrotizing fasciitis secondary to VZV infection. No cases of tuberculosis,
      opportunistic infections, or malignancies were reported. CONCLUSION: In our
      cohort of patients etanercept proved to be safe and efficacious in the majority
      of children. The response in toddlers was similar to that in older children. We
      observed only 1 case of severe infection that required hospitalization and
      stopped treatment temporarily.

PMID- 22589255
TI  - Treatment with biologic agents improves the prognosis of patients with rheumatoid
      arthritis and amyloidosis.
AB  - OBJECTIVE: Reactive amyloid A (AA) amyloidosis is a serious and life-threatening
      systemic complication of rheumatoid arthritis (RA). We evaluated the safety of
      therapy with anti-tumor necrosis factor and anti-interleukin 6 biologic agents in
      RA patients with reactive AA amyloidosis, together with prognosis and
      hemodialysis (HD)-free survival, in comparison with patients with AA amyloidosis
      without such therapy. METHODS: One hundred thirty-three patients with an
      established diagnosis of reactive AA amyloidosis participated in the study.
      Clinical data were assessed from patient records at the time of amyloid detection
      and administration of biologics. Survival was calculated from the date when
      amyloid was first demonstrated histologically or the date when biologic therapy
      was started until the time of death or to the end of 2010 for surviving patients.
      Patients who had started HD were selected for inclusion only after the presence
      of amyloid was demonstrated. RESULTS: Fifty-three patients were treated with
      biologic agents (biologic group) and 80 were not (nonbiologic group). Survival
      rate was significantly higher in the biologic group than in the nonbiologic
      group. Nine patients in the biologics group and 33 in the nonbiologic group
      started HD. Biologic therapy had a tendency for reduced risk of initiation of HD
      without any statistical significance. CONCLUSION: Patients with amyloidosis have
      a higher mortality rate, but the use of biologic agents can reduce risk of death.
      The use of biologics may not significantly influence the HD-free survival rate.

PMID- 22589256
TI  - Evaluation of a shared autoimmune disease-associated polymorphism of TRAF6 in
      systemic sclerosis and giant cell arteritis.
AB  - OBJECTIVE: We evaluated whether a single-nucleotide polymorphism (SNP) of the
      TRAF6 gene previously associated with systemic lupus erythematosus and rheumatoid
      arthritis may be a common risk factor for systemic sclerosis (SSc) and giant cell
      arteritis (GCA). METHODS: A total of 1185 patients with SSc, 479 patients with
      biopsy-proven GCA, and 1442 unrelated healthy controls of white Spanish origin
      were genotyped for the rs540386 variant using a specifically designed TaqMan((c))
      allele discrimination assay. RESULTS: No significant associations of this SNP
      with global SSc or GCA were found. This was also the case when the potential
      associations of the TRAF6 polymorphism with the main clinical phenotypes of the 2
      diseases (e.g., limited cutaneous and diffuse cutaneous SSc, or presence of
      polymyalgia rheumatica and visual ischemic manifestations in GCA) were assessed.
      CONCLUSION: Our data do not support a role of the rs540386 TRAF6 variant as a key
      component of the genetic network underlying SSc and GCA.

PMID- 22589258
TI  - Carotid atherosclerosis, disease measures, oxidized low-density lipoproteins, and
      atheroprotective natural antibodies for cardiovascular disease in early
      rheumatoid arthritis -- an inception cohort study.
AB  - OBJECTIVE: Although an enhanced risk of cardiovascular disease (CVD) in persons
      with rheumatoid arthritis (RA) is well established, the mechanisms behind it
      remain unclear. We studied whether carotid atherosclerosis, RA disease measures,
      or potential cardiovascular biomarkers influenced the incidence of CVD in an RA
      inception cohort. METHODS: RA disease measures and CVD biomarkers were assessed
      at 0, 3, 12, 24, and 60 months after disease onset, and carotid ultrasonography
      after 5 years. The study outcome was incident CVD events - acute myocardial
      infarction, angina pectoris, congestive heart failure, or ischemic
      cerebrovascular event. Survival analysis and Cox and longitudinal regressions
      were used for statistical analyses. RESULTS: A total of 105 patients, without CVD
      events prior to RA onset, experienced 17 CVD events, an incidence rate of 1.35
      events per 100 person-years (95% CI 0.71-2.0). The rate of CVD events did not
      differ with regard to measures of carotid intima-media thickness, but it was
      higher for patients with bilateral carotid plaques than for those without (p =
      0.012). Improvement in Disease Activity Score for 28 joints, visual analog scale
      for pain, and Stanford Health Assessment Questionnaire score over the first year,
      as well as usage of methotrexate (MTX), was associated, independent of age, with
      reduction of risk of CVD event [hazard ratios 0.68 (95% CI 0.5-0.97), 0.97 (95%
      CI 0.95-0.99), 0.35 (95% CI 0.15-0.82), and 0.34 (95% CI 0.12-0.91),
      respectively]. In longitudinal analyses, increasing oxidized low-density
      lipoprotein (oxLDL) and probability for low antiphosphorylcholine antibodies
      (anti-PC) were observed in those who experienced a subsequent CVD event.
      CONCLUSION: Bilateral carotid plaques were associated with poor CVD-free
      survival. Early reductions of inflammation, pain, and disability as well as MTX
      usage were associated with better CVD outcome. Elevated oxLDL and low IgM anti-PC
      levels may link chronic inflammation in RA to enhanced risk of CVD events.

PMID- 22589259
TI  - Psoriatic arthritis and onycholysis -- results from the cross-sectional Reykjavik
      psoriatic arthritis study.
AB  - OBJECTIVE: To measure the associations between subtypes of nail changes and
      psoriatic arthritis (PsA) among patients with psoriasis. METHODS: Patients age 18
      years and older with active psoriasis were examined for skin and nail changes and
      asked if they had been diagnosed with PsA. Patients with arthritis were invited
      for a separate study 1-6 years after their initial visit. Univariate and
      multivariate analyses were used to test the strength of associations between
      subtypes of nail changes and arthritis. RESULTS: Of 1116 patients with psoriasis,
      37% (95% CI 34%-40%) had nail changes. Age, any nail change, onycholysis, and
      pitting were each associated with PsA on univariate analysis. Multivariate
      analysis showed that onycholysis was the only type of nail change independently
      associated with PsA (OR 2.05, p < 0.001). Nail changes persisted and had
      increased in prevalence at the followup examination at a mean of 3.8 (median 4
      yrs, interquartile range 3-4) years later. Previously reported associations
      between psoriasis location and arthritis were not seen in this dataset.
      CONCLUSION: PsA is associated with onycholysis. Associations with pitting and
      subungual hyperkeratosis were not statistically significant. Subtypes of nail
      changes should be analyzed separately in future studies of PsA.

PMID- 22589257
TI  - Increased sensitivity of the European medicines agency algorithm for
      classification of childhood granulomatosis with polyangiitis.
AB  - OBJECTIVE: Granulomatosis with polyangiitis (Wegener's; GPA) and other
      antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare
      in childhood and are sometimes difficult to discriminate. We compared use of
      adult-derived classification schemes for GPA against validated pediatric criteria
      in the ARChiVe (A Registry for Childhood Vasculitis e-entry) cohort, a Childhood
      Arthritis and Rheumatology Research Alliance initiative. METHODS: Time-of
      diagnosis data for children with physician (MD) diagnosis of AAV and unclassified
      vasculitis (UCV) from 33 US/Canadian centers were analyzed. The European
      Medicines Agency (EMA) classification algorithm and European League Against
      Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric
      Rheumatology European Society (EULAR/PRINTO/PRES) and American College of
      Rheumatology (ACR) criteria for GPA were applied to all patients. Sensitivity and
      specificity were calculated (MD-diagnosis as reference). RESULTS: MD-diagnoses
      for 155 children were 100 GPA, 25 microscopic polyangiitis (MPA), 6 ANCA-positive
      pauciimmune glomerulonephritis, 3 Churg-Strauss syndrome, and 21 UCV. Of these,
      114 had GPA as defined by EMA, 98 by EULAR/PRINTO/PRES, and 87 by ACR. Fourteen
      patients were identified as GPA by EULAR/PRINTO/PRES but not by ACR; 3 were
      identified as GPA by ACR but not EULAR/PRINTO/PRES. Using the EMA algorithm, 135
      (87%) children were classifiable. The sensitivity of the EMA algorithm, the
      EULAR/PRINTO/PRES, and ACR criteria for classifying GPA was 90%, 77%, and 69%,
      respectively, with specificities of 56%, 62%, and 67%. The relatively poor
      sensitivity of the 2 criteria related to their inability to discriminate patients
      with MPA. CONCLUSION: EULAR/PRINTO/PRES was more sensitive than ACR criteria in
      classifying pediatric GPA. Neither classification system has criteria for MPA;
      therefore usefulness in discriminating patients in ARChiVe was limited. Even when
      using the most sensitive EMA algorithm, many children remained unclassified.

PMID- 22589260
TI  - Safety of infliximab treatment in patients with rheumatoid arthritis in a real
      world clinical setting: description and evaluation of infusion reactions.
AB  - OBJECTIVE: To describe acute and delayed infusion reactions in a large cohort of
      patients with inflammatory arthritis, treated with infliximab (IFX). METHODS: We
      conducted a retrospective chart review of patients treated with IFX at the Mary
      Pack Arthritis Centre between 2000 and 2008. The primary outcome was the
      occurrence of acute infusion reactions during infusions or 1-2 hours after each
      infusion, and secondary outcome was the occurrence of delayed infusion reactions
      1-14 days after an infusion. Descriptive analyses were conducted to summarize
      study outcomes and identify trends over followup. RESULTS: Since 2000, 376
      patients were referred to the Mary Pack IFX clinic and 200 received 4399 IFX
      infusions over a mean 140 +/- 132 weeks of followup. Of these, 135 were patients
      with RA who received 2977 IFX infusions over mean followup of 138 +/- 132 weeks.
      In total 258 episodes of acute reactions were observed for an overall acute
      reaction rate of 5.8%. Acute infusion reactions were mostly mild (42.6%) and
      moderate (43.8%) and commonly affected sites were head and neck (31.5%) and
      cutaneous (21.1%). A total of 37 delayed infusion reaction episodes were observed
      (0.9% rate); reactions were also mostly mild (16.2%) and moderate (64.9%).
      CONCLUSION: These clinical data from 200 patients treated with IFX demonstrate
      that acute and delayed infusion reactions occur infrequently and are mostly mild
      to moderate in presentation.

PMID- 22589261
TI  - Increased serum interleukin 22 in patients with rheumatoid arthritis and
      correlation with disease activity.
AB  - OBJECTIVE: To analyze the role of interleukin 22 (IL-22) in rheumatoid arthritis
      (RA). METHODS: IL-22 serum levels were measured in 83 patients with established
      RA under treatment with disease-modifying antirheumatic drugs and in 30 healthy
      controls matched for age and sex. Patients were assessed for clinical and
      laboratory variables. Correlations of IL-22 serum levels with disease activity
      measures [Clinical Disease Activity Index (CDAI) and Disease Activity Score for
      28 joints (DAS28)], serological markers, bone erosions, and demographic factors
      were assessed. Peripheral blood mononuclear cells (PBMC) from 30 patients with RA
      and 14 controls were purified and stimulated in vitro with phorbol myristate
      acetate (PMA)/ionomycin. IL-22 production by PBMC and in serum was investigated
      by ELISA. RESULTS: IL-22 levels were increased in patients with RA compared with
      controls (mean 432.37 pg/ml and 67.45 pg/ml, respectively; p < 0.001). Levels of
      IL-22 correlated with DAS28 and CDAI measures. Rheumatoid factor (RF) positivity
      was correlated with higher levels of IL-22 in patients with RA (mean 575.08
      pg/ml; p = 0.001). The presence of bone erosions was associated with high IL-22
      levels (p = 0.0001). PBMC stimulated with PMA/ionomycin expressed higher levels
      of IL-22 in patients with RA than controls but this was not significant (mean
      584.75 pg/ml and 295.57 pg/ml; p = 0.553). CONCLUSION: IL-22 is elevated in the
      serum of patients with established RA. Elevated serum IL-22 allows discrimination
      between patients with different clinical and laboratory measures and indicates
      the potential of IL-22 as an additional tool for assessment of activity in RA,
      particularly in patients with RF antibodies and longterm disease. IL-22 is
      associated with bone-destructive disease.

PMID- 22589262
TI  - Validity and reliability problems with patient global as a component of the
      ACR/EULAR remission criteria as used in clinical practice.
AB  - OBJECTIVE: To investigate what factors influence patient global health assessment
      (PtGlobal), and how those factors and the reliability of PtGlobal affect the
      rate, reliability, and validity of recently published American College of
      Rheumatology/European League Against Rheumatism (ACR/EULAR) rheumatoid arthritis
      (RA) remission criteria when used in clinical practice. METHODS: We examined
      consecutive patients with RA in clinical practice and identified 77 who met
      ACR/EULAR joint criteria for remission (<= 1 swollen joint and <= 1 tender
      joint). We evaluated factors associated with a PtGlobal > 1, because a PtGlobal
      <= 1 defined ACR/EULAR remission in this group of patients who had already met
      ACR/EULAR joint criteria. RESULTS: Of the 77 patients examined, only 17 (22.1%)
      had PtGlobal <= 1 and thus fully satisfied ACR/EULAR criteria. A large proportion
      of patients not in remission by ACR/EULAR criteria had high PtGlobal related to
      noninflammatory issues, including low back pain, fatigue, and functional
      limitations, and a number of patients clustered in the range of PtGlobal > 1 and
      <= 2. However, the minimal detectable difference for PtGlobal was 2.3. In
      addition, compared with a PtGlobal severity score, a PtGlobal activity score was
      3.3% less likely to be abnormal (> 1). CONCLUSION: Noninflammatory factors
      contribute to the level of PtGlobal and result in the exclusion of many patients
      who would otherwise be in "true" remission according to the ACR/EULAR definition.
      Reliability problems associated with PtGlobal can also result in
      misclassification, and may explain the observation of low longterm remission
      rates in RA. As currently constituted, the use of the ACR/EULAR remission
      criteria in clinical practice appears to be problematic.

PMID- 22589263
TI  - Comparison of the diagnostic utility of cardiac magnetic resonance imaging,
      computed tomography, and echocardiography in assessment of suspected pulmonary
      arterial hypertension in patients with connective tissue disease.
AB  - OBJECTIVE: Pulmonary arterial hypertension (PAH) is a life-threatening
      complication of connective tissue diseases (CTD). Our aim was to compare the
      diagnostic utility of noninvasive imaging modalities, i.e., magnetic resonance
      imaging (MRI), computed tomography (CT), and echocardiography, in evaluation of
      these patients. METHODS: In total, 81 consecutive patients with CTD and suspected
      PH underwent cardiac MRI, CT, and right heart catheterization (RHC) within 48
      hours. Functional cardiac MRI variables [ventricle areas and ratios, delayed
      myocardial enhancement, position of the interventricular septum, right
      ventricular mass, ventricular mass index (VMI), and pulmonary artery
      distensibility] were all evaluated. The pulmonary artery size, pulmonary
      artery/aortic ratio (PA/Ao), left and right ventricular (RV) diameter ratio, RV
      wall thickness, and grade of tricuspid regurgitation were measured on CT.
      Tricuspid gradient (TG) and size of the RV were assessed using echocardiography.
      RESULTS: In our study of 81 patients with CTD, 55 had PAH, 22 had no PH, and 4
      had PH owing to left heart disease. There was good correlation between mean
      pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) measured
      by RHC and VMI derived from MRI (mPAP, r = 0.69, p < 0.001; PVR, r = 0.78, p <
      0.001) and systolic area ratio (mPAP, r = 0.69, p < 0.001; PVR, r = 0.68, p <
      0.001) and TG derived from echocardiography (mPAP, r = 0.84, p < 0.001; PVR, r =
      0.76, p < 0.001). In contrast, CT measures showed only moderate correlation. MRI
      and echocardiography each performed better as a diagnostic test for PAH than CT
      derived measures: VMI >= 0.45 had a sensitivity of 85% and specificity 82%; and
      TG >= 40 mm Hg had a sensitivity of 86% and specificity 82%. Univariate Cox
      regression analysis showed the MRI measurements were better at predicting
      mortality. Patients with RV end diastolic volume < 135 ml had a better prognosis
      than those with a value > 135 ml, with a 1-year survival of 95% versus 66%,
      respectively. CONCLUSION: In patients with CTD and suspected PAH, cardiac MRI and
      echocardiography have greater diagnostic utility than CT in the assessment of
      patients with suspected PAH, and MRI has prognostic value.

PMID- 22589264
TI  - CCL18 -- potential biomarker of fibroinflammatory activity in chronic
      periaortitis.
AB  - OBJECTIVE: Promising therapeutic approaches have emerged in chronic periaortitis,
      whereas peripheral blood biomarkers are lacking. CC-chemokine ligand 18 (CCL18)
      is known as a marker of fibrotic activity and prognosis in pulmonary fibrosis. We
      investigated whether CCL18 levels are increased in patients with chronic
      periaortitis and are associated with clinical, laboratory, and imaging findings.
      METHODS: In this retrospective study, serum concentrations of CCL18 were assessed
      in 30 patients with chronic periaortitis and related to clinical data, laboratory
      variables, and imaging studies. Serum levels were compared to 15 apparently
      healthy volunteers and 15 controls with aortic sclerosis. RESULTS: Serum
      concentrations of CCL18 were increased in patients with chronic periaortitis
      (median 197.6 ng/ml, range 73.7-301.0) compared to healthy volunteers (median
      34.6 ng/ml, range 22.6-70.4; p < 0.0001) and controls with aortic sclerosis
      (median 50.4 ng/ml, range 24.5-141.2; p < 0.0001). CCL18 levels correlated with
      (n = 30; r = 0.461, p = 0.01) and increased with the transversal diameter of the
      periaortic mantle < 5, 5-10, and >= 10 mm (p = 0.008). Contrast enhancement (p =
      0.044), treatment naivety (p = 0.042), and the occurrence of systemic symptoms (p
      = 0.007) were associated with higher CCL18 levels. During followup, changes of
      CCL18 correlated with changes of the transverse diameter of the periaortic mantle
      (n = 17; r = 0.512, p = 0.033). CONCLUSION: Serum concentration of CCL18 reflects
      fibroinflammatory activity and extent of disease in patients with chronic
      periaortitis.

PMID- 22589265
TI  - Timing and magnitude of initial change in disease activity score 28 predicts the
      likelihood of achieving low disease activity at 1 year in rheumatoid arthritis
      patients treated with certolizumab pegol: a post-hoc analysis of the RAPID 1
      trial.
AB  - OBJECTIVE: To determine the relationship between timing and magnitude of Disease
      Activity Score [DAS28(ESR)] nonresponse (DAS28 improvement thresholds not
      reached) during the first 12 weeks of treatment with certolizumab pegol (CZP)
      plus methotrexate, and the likelihood of achieving low disease activity (LDA) at
      1 year in patients with rheumatoid arthritis. METHODS: In a post-hoc analysis of
      the RAPID 1 study, patients achieving LDA [DAS28(ESR) <= 3.2] at Year 1 were
      assessed according to DAS28 nonresponse at various timepoints within the first 12
      weeks. RESULTS: Seven-hundred eighty-three patients were included (CZP 200 mg, n
      = 393; CZP 400 mg, n = 390). A total of 86.9% of patients in the CZP 200 mg group
      had a DAS28 improvement of >= 1.2 by Week 12. Of the 13.1% of patients with DAS28
      improvement < 1.2 by Week 12, only 2.0% had LDA at Year 1. Failure to achieve LDA
      at Year 1 depended on timing of nonresponse - 22.3%, 8.4%, and 2.0% of patients
      with DAS28 improvement < 1.2 by Weeks 1, 6, and 12, respectively, had LDA at Year
      1 - and magnitude of initial lack of DAS28 improvement; for example, compared
      with the patients with DAS28 < 1.2 improvement, fewer patients with DAS28 < 0.6
      had LDA at Year 1 (17.4%, 2.4%, and 0.0% at Weeks 1, 6, and 12, respectively).
      CONCLUSION: Failure to achieve improvement in DAS28 within the first 12 weeks of
      therapy was predictive of a low probability of achieving LDA at Year 1. Moreover,
      the accuracy of the prediction was found to be strongly dependent on the
      magnitude and timing of the lack of the response. (Clinical Trial Registration
      Nos. NCT00152386 and NCT00175877).

PMID- 22589267
TI  - Mitochondrial DNA copy number in peripheral blood is associated with femoral neck
      bone mineral density in postmenopausal women.
AB  - OBJECTIVE: It has been suggested that mitochondrial dysfunction is related to
      aging and metabolic disorders. Yet there are few studies of the relationship
      between bone mineral density (BMD) and mitochondrial content in humans. We
      investigated the relationship between BMD and mitochondrial DNA (mtDNA) copy
      number in peripheral blood of postmenopausal women. METHODS: The study included
      146 postmenopausal women. Enrolled subjects were taking no medications and had no
      disorders that altered bone metabolism. We measured BMD using dual-energy x-ray
      absorptiometry and leukocyte mtDNA copy number using real-time polymerase chain
      reaction. Anthropometric evaluations and biochemical tests were performed.
      RESULTS: Patients with osteopenia or osteoporosis had lower mtDNA copy numbers
      than normal subjects (p < 0.0001). Femoral neck BMD was negatively correlated
      with age (r = -0.01, p = 0.04) and with serum levels of adiponectin (r = -0.22, p
      = 0.01) and osteocalcin (r = -0.31, p = 0.0001). Serum levels of 25-OH vitamin D
      (r = 0.32, p < 0.0001) and mtDNA copy number (r = 0.36, p < 0.0001) were
      positively correlated with femoral neck BMD. Multiple regression analysis showed
      that mtDNA copy number (beta = 0.156, p < 0.001) was an independent factor
      associated with femoral neck BMD after adjustment for age, body mass index, waist
      circumference, waist-hip ratio, blood pressure, homeostatic model assessment of
      insulin resistance, high-sensitivity C-reactive protein, adiponectin,
      osteocalcin, homocysteine, lipid profiles, 25-OH vitamin D, and regular exercise.
      mtDNA copy number was not related to lumbar BMD. CONCLUSION: Low mtDNA content in
      peripheral blood is related to decreased femoral neck BMD in postmenopausal
      women. Our findings suggest that mitochondrial dysfunction may be a potential
      pathophysiologic mechanism of osteoporosis in postmenopausal women.

PMID- 22589266
TI  - Cigarette smoking, alcohol consumption, and risk of systemic lupus erythematosus:
      a case-control study in a Japanese population.
AB  - OBJECTIVE: Cigarette smoking may be associated with increased risk of systemic
      lupus erythematosus (SLE), whereas the role of alcohol consumption is unknown. We
      examined the association between SLE risk and smoking or drinking. METHODS: We
      investigated the relationship of smoking and drinking compared to SLE risk among
      171 SLE cases and 492 healthy controls in female Japanese subjects. Unconditional
      logistic regression was used to compute OR and 95% CI, with adjustments for
      several covariates. RESULTS: Compared with nonsmoking, current smoking was
      significantly associated with increased risk of SLE (OR 3.06, 95% CI 1.86-5.03).
      The higher the level of exposure to cigarette smoke, the higher the risk of SLE.
      Inhalation was also associated with increased SLE risk (OR 3.73, 95% CI 1.46-9.94
      for moderate inhalation; OR 3.06, 95% CI 1.81-5.15 for deep inhalation). In
      contrast, light/moderate alcohol consumption had a protective effect on SLE risk
      (OR 0.38, 95% CI 0.19-0.76). As for beer, the risks for non-beer drinkers and
      beer drinkers were similar. This also applies to alcoholic beverages other than
      beer. CONCLUSION: Our results suggest that smoking was positively associated with
      increased SLE risk whereas light/moderate alcohol consumption was inversely
      associated with SLE risk, irrespective of the type of alcoholic beverage.
      Additional studies are warranted to confirm these findings.

PMID- 22589268
TI  - Risk factors for temporomandibular joint arthritis in children with juvenile
      idiopathic arthritis.
AB  - OBJECTIVE: To determine the prevalence and features of temporomandibular joint
      (TMJ) arthritis by magnetic resonance imaging (MRI) among children with juvenile
      idiopathic arthritis (JIA), and to identify risk factors for TMJ arthritis.
      METHODS: A retrospective chart review was performed on 187 patients with JIA who
      underwent a TMJ MRI at Children's Hospital of Alabama between September 2007 and
      June 2010. Demographic and clinical information was abstracted from the charts.
      Univariate and multivariate analyses were performed to identify risk factors for
      TMJ arthritis identified by MRI. RESULTS: MRI evidence of TMJ arthritis was
      detected in 43% of patients, with no significant difference among JIA categories.
      The number of joints with active arthritis (exclusive of the TMJ) and the use of
      systemic immunomodulatory therapies were not associated with TMJ arthritis.
      Multivariable analysis revealed a strong association between mouth-opening
      deviation and TMJ arthritis (OR 6.21, 95% CI 2.87-13.4). A smaller maximal
      incisal opening and shorter disease duration were also associated with an
      increased risk of TMJ arthritis. CONCLUSION: TMJ arthritis was identified in a
      substantial proportion of children with JIA (43%) and affects all JIA categories.
      TMJ arthritis was present in some patients despite limited or otherwise quiescent
      disease and in the presence of concurrent systemic immunomodulatory therapy.
      Routine evaluation for TMJ arthritis by MRI is warranted for all children with
      JIA.

PMID- 22589270
TI  - A comprehensive survey of Ras mutations in cancer.
AB  - All mammalian cells express 3 closely related Ras proteins, termed H-Ras, K-Ras,
      and N-Ras, that promote oncogenesis when they are mutationally activated at codon
      12, 13, or 61. Although there is a high degree of similarity among the isoforms,
      K-Ras mutations are far more frequently observed in cancer, and each isoform
      displays preferential coupling to particular cancer types. We examined the
      mutational spectra of Ras isoforms curated from large-scale tumor profiling and
      found that each isoform exhibits surprisingly distinctive codon mutation and
      amino-acid substitution biases. These findings were unexpected given that these
      mutations occur in regions that share 100% amino-acid sequence identity among the
      3 isoforms. Of importance, many of these mutational biases were not due to
      differences in exposure to mutagens, because the patterns were still evident when
      compared within specific cancer types. We discuss potential genetic and
      epigenetic mechanisms, as well as isoform-specific differences in protein
      structure and signaling, that may promote these distinct mutation patterns and
      differential coupling to specific cancers.

PMID- 22589271
TI  - SIRT3 is a mitochondrial tumor suppressor: a scientific tale that connects
      aberrant cellular ROS, the Warburg effect, and carcinogenesis.
AB  - Tumors exhibit metabolic reprogramming characterized by increased cellular
      reactive oxygen species (ROS) and the preferential use of glucose, which is known
      as the Warburg effect. However, the mechanisms by which these processes are
      linked remain largely elusive. Murine tumors lacking Sirt3 exhibit abnormally
      high levels of ROS that directly induce genomic instability and increase hypoxia
      inducible factor 1alpha (HIF-1alpha) protein levels. The subsequent transcription
      of HIFalpha-dependent target genes results in cellular metabolic reprogramming
      and increased cellular glucose consumption. In addition, agents that scavenge ROS
      or reverse the Warburg effect prevent the transformation and malignant phenotype
      observed in cells lacking Sirt3. Thus, mice lacking Sirt3 provide a model that
      mechanistically connects aberrant ROS, the Warburg effect, and carcinogenesis.

PMID- 22589272
TI  - Identification of serum biomarker signatures associated with pancreatic cancer.
AB  - Pancreatic cancer is an aggressive disease with poor prognosis, due, in part, to
      the lack of disease-specific biomarkers that could afford early and accurate
      diagnosis. With a recombinant antibody microarray platform, targeting mainly
      immunoregulatory proteins, we screened sera from 148 patients with pancreatic
      cancer, chronic pancreatitis, autoimmune pancreatitis (AIP), and healthy controls
      (N). Serum biomarker signatures were derived from training cohorts and the
      predictive power was evaluated using independent test cohorts. The results
      identified serum portraits distinguishing pancreatic cancer from N [receiver
      operating characteristics area under the curve (AUC) of 0.95], chronic
      pancreatitis (0.86), and AIP (0.99). Importantly, a 25-serum biomarker signature
      discriminating pancreatic cancer from the combined group of N, chronic
      pancreatitis, and AIP was determined. This signature exhibited a high diagnostic
      potential (AUC of 0.88). In summary, we present the first prevalidated,
      multiplexed serum biomarker signature for diagnosis of pancreatic cancer that may
      improve diagnosis and prevention in premalignant diseases and in screening of
      high-risk individuals.

PMID- 22589273
TI  - Cyclophosphamide creates a receptive microenvironment for prostate cancer
      skeletal metastasis.
AB  - A number of cancers predominantly metastasize to bone, due to its complex
      microenvironment and multiple types of constitutive cells. Prostate cancer
      especially has been shown to localize preferentially to bones with higher marrow
      cellularity. Using an experimental prostate cancer metastasis model, we
      investigated the effects of cyclophosphamide, a bone marrow-suppressive
      chemotherapeutic drug, on the development and growth of metastatic tumors in
      bone. Priming the murine host with cyclophosphamide before intracardiac tumor
      cell inoculation was found to significantly promote tumor localization and
      subsequent growth in bone. Shortly after cyclophosphamide treatment, there was an
      abrupt expansion of myeloid lineage cells in the bone marrow and the peripheral
      blood, associated with increases in cytokines with myelogenic potential such as C
      C chemokine ligand (CCL)2, interleukin (IL)-6, and VEGF-A. More importantly,
      neutralizing host-derived murine CCL2, but not IL-6, in the premetastatic murine
      host significantly reduced the prometastatic effects of cyclophosphamide.
      Together, our findings suggest that bone marrow perturbation by cytotoxic
      chemotherapy can contribute to bone metastasis via a transient increase in bone
      marrow myeloid cells and myelogenic cytokines. These changes can be reversed by
      inhibition of CCL2.

PMID- 22589274
TI  - KRas induces a Src/PEAK1/ErbB2 kinase amplification loop that drives metastatic
      growth and therapy resistance in pancreatic cancer.
AB  - Early biomarkers and effective therapeutic strategies are desperately needed to
      treat pancreatic ductal adenocarcinoma (PDAC), which has a dismal 5-year patient
      survival rate. Here, we report that the novel tyrosine kinase PEAK1 is
      upregulated in human malignancies, including human PDACs and pancreatic
      intraepithelial neoplasia (PanIN). Oncogenic KRas induced a PEAK1-dependent
      kinase amplification loop between Src, PEAK1, and ErbB2 to drive PDAC tumor
      growth and metastasis in vivo. Surprisingly, blockade of ErbB2 expression
      increased Src-dependent PEAK1 expression, PEAK1-dependent Src activation, and
      tumor growth in vivo, suggesting a mechanism for the observed resistance of
      patients with PDACs to therapeutic intervention. Importantly, PEAK1 inactivation
      sensitized PDAC cells to trastuzumab and gemcitabine therapy. Our findings,
      therefore, suggest that PEAK1 is a novel biomarker, critical signaling hub, and
      new therapeutic target in PDACs.

PMID- 22589275
TI  - Mitochondrial Bcl-2 family dynamics define therapy response and resistance in
      neuroblastoma.
AB  - Neuroblastoma is a childhood tumor in which transient therapeutic responses are
      typically followed by recurrence with lethal chemoresistant disease. In this
      study, we characterized the apoptotic responses in diverse neuroblastomas using
      an unbiased mitochondrial functional assay. We defined the apoptotic set point of
      neuroblastomas using responses to distinct BH3 death domains providing a BH3
      response profile and directly confirmed survival dependencies. We found that
      viable neuroblastoma cells and primary tumors are primed for death with tonic
      sequestration of Bim, a direct activator of apoptosis, by either Bcl-2 or Mcl-1,
      providing a survival dependency that predicts the activity of Bcl-2 antagonists.
      The Bcl-2/Bcl-xL/Bcl-w inhibitor ABT-737 showed single-agent activity against
      only Bim:Bcl-2 primed tumor xenografts. Durable complete regressions were
      achieved in combination with noncurative chemotherapy even for highest risk
      molecular subtypes with MYCN amplification and activating ALK mutations.
      Furthermore, the use of unique isogenic cell lines from patients at diagnosis and
      at the time of relapse showed that therapy resistance was not mediated by
      upregulation of Bcl-2 homologues or loss of Bim priming, but by repressed Bak/Bax
      activation. Together, our findings provide a classification system that
      identifies tumors with clinical responses to Bcl-2 antagonists, defines Mcl-1 as
      the principal mediator of Bcl-2 antagonist resistance at diagnosis, and isolates
      the therapy resistant phenotype to the mitochondria.

PMID- 22589276
TI  - Loss of cell-surface laminin anchoring promotes tumor growth and is associated
      with poor clinical outcomes.
AB  - Perturbations in the composition and assembly of extracellular matrices (ECM)
      contribute to progression of numerous diseases, including cancers. Anchoring of
      laminins at the cell surface enables assembly and signaling of many ECMs, but the
      possible contributions of altered laminin anchoring to cancer progression remain
      undetermined. In this study, we investigated the prominence and origins of
      defective laminin anchoring in cancer cells and its association with cancer
      subtypes and clinical outcomes. We found loss of laminin anchoring to be
      widespread in cancer cells. Perturbation of laminin anchoring originated from
      several distinct defects, which all led to dysfunctional glycosylation of the ECM
      receptor dystroglycan. In aggressive breast and brain cancers, defective laminin
      anchoring was often due to suppressed expression of the glycosyltransferase
      LARGE. Reduced expression of LARGE characterized a broad array of human tumors in
      which it was associated with aggressive cancer subtypes and poor clinical
      outcomes. Notably, this defect robustly predicted poor survival in patients with
      brain cancers. Restoring LARGE expression repaired anchoring of exogenous and
      endogenous laminin and modulated cell proliferation and tumor growth. Together,
      our findings suggest that defects in laminin anchoring occur commonly in cancer
      cells, are characteristic of aggressive cancer subtypes, and are important
      drivers of disease progression.

PMID- 22589277
TI  - Dinitroazetidines are a novel class of anticancer agents and hypoxia-activated
      radiation sensitizers developed from highly energetic materials.
AB  - In an effort to develop cancer therapies that maximize cytotoxicity, while
      minimizing unwanted side effects, we studied a series of novel compounds based on
      the highly energetic heterocyclic scaffold, dinitroazetidine. In this study, we
      report the preclinical validation of 1-bromoacetyl-3,3-dinitroazetidine (ABDNAZ),
      a representative lead compound currently in a phase I clinical trial in patients
      with cancer. In tumor cell culture, ABDNAZ generated reactive free radicals in a
      concentration- and time-dependent manner, modulating intracellular redox status
      and triggering apoptosis. When administered to mice as a single agent, ABDNAZ
      exhibited greater cytotoxicity than cisplatin or tirapazamine under hypoxic
      conditions. However, compared with cisplatin, ABDNAZ was better tolerated at
      submaximal doses, yielding significant tumor growth inhibition in the absence of
      systemic toxicity. Similarly, when combined with radiation, ABDNAZ accentuated
      antitumor efficacy along with the therapeutic index. Toxicity studies indicated
      that ABDNAZ was not myelosuppressive and no dose-limiting toxicity was apparent
      following daily administration for 14 days. Taken together, our findings offer
      preclinical proof-of-concept for ABDNAZ as a promising new anticancer agent with
      a favorable toxicity profile, either as a chemotherapeutic agent or a
      radiosensitizer.

PMID- 22589278
TI  - Reduced spiking in entorhinal cortex during the delay period of a cued spatial
      response task.
AB  - Intrinsic persistent spiking mechanisms in medial entorhinal cortex (mEC) neurons
      may play a role in active maintenance of working memory. However,
      electrophysiological studies of rat mEC units have primarily focused on spatial
      modulation. We sought evidence of differential spike rates in the mEC in rats
      trained on a T-maze, cued spatial delayed response task. Animals begin at the
      base of the T-maze where a 1-sec white noise and visual light cue are presented
      on the left or right side of the maze. Rats are rewarded for responding toward
      the cued direction. In correct trials, we observed decreased spike rates during
      the delay period, the time interval between cue presentation and reward delivery.
      Firing-rate histograms show significant decreases during the delay period
      compared to 5-sec windows from both pre-cue and post-reward periods. We analyzed
      how running speed and trajectory specificity correlated to spike rate. Twice as
      many cells were responsive to cue alone compared to running speed. Trajectory
      specificity did not relate significantly to firing rate. Decreased spike rate may
      reflect active maintenance in other structures inhibiting mEC. Alternately, the
      reduction may reflect decreases in background activity during enhanced attention
      and cholinergic modulation. Lastly, animals often ran through the T-maze choice
      point with varying speed. We calculated the spatial posterior probability density
      from spike rates during these choice-point passes. Slow passes through the choice
      point were characterized by greater probability of decoding to the reward
      locations on correct trials compared to quick passes on the maze consistent with
      similar "look-ahead" properties previously reported in the hippocampus and
      ventral striatum.

PMID- 22589279
TI  - Post-acquisition release of glutamate and norepinephrine in the amygdala is
      involved in taste-aversion memory consolidation.
AB  - Amygdala activity mediates the acquisition and consolidation of emotional
      experiences; we have recently shown that post-acquisition reactivation of this
      structure is necessary for the long-term storage of conditioned taste aversion
      (CTA). However, the specific neurotransmitters involved in such reactivation are
      not known. The aim of the present study was to investigate extracellular changes
      of glutamate, norepinephrine, and dopamine within the rat amygdala using in vivo
      microdialysis during the acquisition and 1-h post-acquisition of CTA paradigm.
      Microdialysis monitoring showed a significant norepinephrine increase related to
      novel taste exposure and a glutamate increase after gastric malaise induction by
      i.p. LiCl administration. Interestingly, we found a spontaneous concomitant
      increase of glutamate and norepinephrine, but not dopamine, 45 min after
      conditioning, suggesting the presence of aversive learning-dependent post
      acquisition signals in the amygdala. These signals seem to be involved in CTA
      consolidation process, since post-trial blockade of N-methyl-D-aspartate or beta
      adrenergic receptors impaired long- but not short-term memory. These data suggest
      that CTA long-term storage involves post-acquisition release of glutamate and
      norepinephrine in the amygdala.

PMID- 22589281
TI  - The Million HeartsTM initiative: why psychosocial nurses should care.

PMID- 22589285
TI  - Mapping data predictors of a left ventricular outflow tract origin of idiopathic
      ventricular tachycardia with V3 transition and septal earliest activation.
AB  - BACKGROUND: The proximity of the outflow tracts (OTs) frequently results in an
      overlap in surface electrocardiographic features of ventricular arrhythmias
      originating from this anatomic region, particularly when the transition occurs in
      lead V3. In addition, no reliable criteria to discriminate between a right
      ventricular OT (RVOT) and a left ventricular OT (LVOT) site of origin (SOO) are
      derived from intracardiac mapping. METHODS AND RESULTS: A series of 15 patients
      underwent ablation because of OT ventricular arrhythmias having a V3 transition,
      and a septal earliest activation on the RVOT was included in the study.
      Electrocardiographic and mapping data were collected to analyze accuracy in
      predicting the RVOT versus the LVOT SOO of the ventricular arrhythmia. A 10-ms
      isochronal map area in the RVOT was smaller in the RVOT SOO group (1.2 [0.4-2.1]
      versus 3.4 [2.4-3.9] cm2, respectively; P=0.004) and had a shorter perpendicular
      diameter (13 [7-17] versus 28 [20-29] mm; P=0.001) and a higher
      longitudinal/perpendicular axis ratio (1.04 [0.95-1.11] versus 0.49 [0.44-0.57];
      P=0.001). A 10-ms isochronal map area>2.3 cm2 predicted an LVOT origin with 85.7%
      sensitivity and 87.5% specificity, whereas a longitudinal/perpendicular axis
      ratio<0.8 predicted an LVOT origin with 100% sensitivity and 100% specificity.
      Electrocardiography-derived parameters showed lower values of sensitivity and
      specificity. The distal coronary sinus activation mapping did not permit
      distinction between RVOT and LVOT SOO. CONCLUSIONS: The 10-ms isochronal map area
      and the longitudinal/perpendicular axis ratio accurately predict the RVOT versus
      the LVOT SOO in patients with OT ventricular arrhythmias, a V3 transition, and a
      septal earliest activation.

PMID- 22589286
TI  - Acute hemodynamic effect of left ventricular endocardial pacing in cardiac
      resynchronization therapy: assessment by pressure-volume loops.
AB  - BACKGROUND: During cardiac resynchronization therapy (CRT) device implantation,
      the pacing lead is usually positioned in the coronary sinus (CS) to stimulate the
      left ventricular (LV) epicardium. Transvenous LV endocardial pacing via
      transseptal puncture has been proposed as an alternative method. In the present
      study, we evaluated the acute hemodynamic effects of CRT through LV endocardial
      pacing in heart failure patients by analyzing LV pressure-volume relationships.
      METHODS AND RESULTS: LV pressure and volume data were determined via conductance
      catheter during CRT device implantation in 10 patients. In addition to the
      standard epicardial CS pacing, the following endocardial LV sites were
      systematically assessed: the site transmural to the CS lead, the LV apex, the
      septal midwall, the basal lateral free wall, and the midlateral free wall. Four
      atrioventricular delays were tested. There was a significant improvement of
      systolic function with CRT in all LV pacing configurations, whereas no
      differences in systolic or diastolic function were detected between LV epicardial
      and endocardial transmural sites. The optimal pacing site varied among patients
      but was rarely related to relatively longer activation delays, as assessed by
      analyzing endocardial electric activation maps. Nonetheless, positioning the
      pacing lead at the optimal endocardial LV site in each patient significantly
      improved LV performance in comparison with conventional CS site stimulation
      (stroke volume, 83 [79-112] mL versus 73 [62-89] mL; P=0.034). CONCLUSIONS:
      Pacing at the optimal individual LV endocardial site yields enhanced LV
      performance in comparison with conventional CS site stimulation. Endocardial LV
      pacing might constitute an alternative approach to CRT, when CS pacing is not
      viable.

PMID- 22589287
TI  - The chimeric genome of Sphaerochaeta: nonspiral spirochetes that break with the
      prevalent dogma in spirochete biology.
AB  - Spirochaetes is one of a few bacterial phyla that are characterized by a unifying
      diagnostic feature, namely, the helical morphology and motility conferred by
      axial periplasmic flagella. Their unique morphology and mode of propulsion also
      represent major pathogenicity factors of clinical spirochetes. Here we describe
      the genome sequences of two coccoid isolates of the recently described genus
      Sphaerochaeta which are members of the phylum Spirochaetes based on 16S rRNA gene
      and whole-genome phylogenies. Interestingly, the Sphaerochaeta genomes completely
      lack the motility and associated signal transduction genes present in all
      sequenced spirochete genomes. Additional analyses revealed that the lack of
      flagella is associated with a unique, nonrigid cell wall structure hallmarked by
      a lack of transpeptidase and transglycosylase genes, which is also unprecedented
      in spirochetes. The Sphaerochaeta genomes are highly enriched in fermentation and
      carbohydrate metabolism genes relative to other spirochetes, indicating a
      fermentative lifestyle. Remarkably, most of the enriched genes appear to have
      been acquired from nonspirochetes, particularly clostridia, in several massive
      horizontal gene transfer events (>40% of the total number of genes in each
      genome). Such a high level of direct interphylum genetic exchange is extremely
      rare among mesophilic organisms and has important implications for the assembly
      of the prokaryotic tree of life. IMPORTANCE: Spiral shape and motility
      historically have been the unifying hallmarks of the phylum Spirochaetes. These
      features also represent important virulence factors of highly invasive pathogenic
      spirochetes such as the causative agents of syphilis and Lyme disease. Through
      the integration of genome sequencing, microscopy, and physiological studies, we
      conclusively show that the spiral morphology and motility of spirochetes are not
      universal morphological properties. In particular, we found that the genomes of
      the members of the recently described genus Sphaerochaeta lack the genes encoding
      the characteristic flagellar apparatus and, in contrast to most other
      spirochetes, have acquired many metabolic and fermentation genes from clostridia.
      These findings have major implications for the isolation and study of
      spirochetes, the diagnosis of spirochete-caused diseases, and the reconstruction
      of the evolutionary history of this important bacterial phylum. The Sphaerochaeta
      sp. genomes offer new avenues to link ecophysiology with the functionality and
      evolution of the spirochete flagellar apparatus.

PMID- 22589288
TI  - Ethanolamine controls expression of genes encoding components involved in
      interkingdom signaling and virulence in enterohemorrhagic Escherichia coli
      O157:H7.
AB  - Bacterial pathogens must be able to both recognize suitable niches within the
      host for colonization and successfully compete with commensal flora for nutrients
      in order to establish infection. Ethanolamine (EA) is a major component of
      mammalian and bacterial membranes and is used by pathogens as a carbon and/or
      nitrogen source in the gastrointestinal tract. The deadly human pathogen
      enterohemorrhagic Escherichia coli O157:H7 (EHEC) uses EA in the intestine as a
      nitrogen source as a competitive advantage for colonization over the microbial
      flora. Here we show that EA is not only important for nitrogen metabolism but
      that it is also used as a signaling molecule in cell-to-cell signaling to
      activate virulence gene expression in EHEC. EA in concentrations that cannot
      promote growth as a nitrogen source can activate expression of EHEC's repertoire
      of virulence genes. The EutR transcription factor, known to be the receptor of
      EA, is only partially responsible for this regulation, suggesting that yet
      another EA receptor exists. This important link of EA with metabolism, cell-to
      cell signaling, and pathogenesis, highlights the fact that a fundamental means of
      communication within microbial communities relies on energy production and
      processing of metabolites. Here we show for the first time that bacterial
      pathogens not only exploit EA as a metabolite but also coopt EA as a signaling
      molecule to recognize the gastrointestinal environment and promote virulence
      expression. IMPORTANCE: In order to successfully cause disease, a pathogen must
      be able to sense a host environment and modulate expression of its virulence
      genes as well as compete with the indigenous microbiota for nutrients.
      Ethanolamine (EA) is present in the large intestine due to the turnover of
      intestinal cells. Here, we show that the human pathogen Escherichia coli O157:H7,
      which causes bloody diarrhea and hemolytic-uremic syndrome, regulates virulence
      gene expression through EA metabolism and by responding to EA as a signal. These
      findings provide the first information directly linking EA with bacterial
      pathogenesis.

PMID- 22589290
TI  - Foldable iris-fixated phakic intraocular lens vs femtosecond laser-assisted LASIK
      for myopia between -6.00 and -9.00 diopters.
AB  - PURPOSE: To compare visual, refractive, and clinical outcomes of foldable iris
      fixated phakic intraocular lens (PIOL) implantation versus femtosecond laser
      assisted LASIK for myopia between -6.00 and -9.00 diopters (D). METHODS: Forty
      six myopic patients were randomized to undergo bilateral Artiflex (Ophtec BV)
      PIOL implantation or bilateral femtosecond laser-assisted conventional LASIK with
      the VISX S2 (Abbott Medical Optics). Refraction, uncorrected (UDVA) and corrected
      (CDVA) distance visual acuity, contrast sensitivity, corneal endothelial cell
      count, rate of retreatment, and complications were compared. RESULTS: Twelve
      months after surgery, no statistically significant differences were noted in
      spherical equivalent refraction (P=.19) or UDVA (P=.28), whereas CDVA was better
      in the PIOL group (P<.001). Spherical equivalent refraction was within +/-0.50 D
      in 42 (91.3%) LASIK eyes and 41 (89.1%) PIOL eyes (P>.99). The percentage of eyes
      gaining lines of CDVA was significantly higher in the PIOL group (50.0% vs 8.7%;
      P<.001). Contrast sensitivity was better for PIOL eyes at 1.5 cycles per degree
      (cpd) (P=.03) and 6 cpd (P=.008). The LASIK eyes showed a mean endothelial cell
      count increase of 3.7%+/-2.8%, whereas PIOL eyes showed a mean decrease of 9.1%+/
      2.0% (P<.001). The rate of retreatment was similar (P=.37), and no serious
      complications occurred in either group. CONCLUSIONS: The Artiflex PIOL provided
      better CDVA and contrast sensitivity at high spatial frequencies than femtosecond
      laser-assisted conventional LASIK, suggesting that PIOL implantation is a
      reasonable option for myopia between -6.00 and -9.00 D.

PMID- 22589289
TI  - Identification of genes in the sigma22 regulon of Pseudomonas aeruginosa required
      for cell envelope homeostasis in either the planktonic or the sessile mode of
      growth.
AB  - The Pseudomonas aeruginosa extracytoplasmic functioning (ECF) sigma factor
      sigma(22) is encoded by algT/algU and is inhibited by anti-sigma factor MucA.
      sigma(22) was originally discovered for its essential role in the expression of
      the exopolysaccharide alginate by mucoid strains associated with chronic
      pulmonary infection. However, sigma(22) is now known to also have a large regulon
      associated with the response to cell wall stress. Our recent transcriptome
      analysis identified 293 open reading frames (ORFs) in the sigma(22) stress
      stimulon that include genes for outer envelope biogenesis and remodeling,
      although most of the genes have undefined functions. To better understand the
      sigma(22)-dependent stress response, mutants affected in 27 genes of the
      sigma(22) stimulon were examined and expression was studied with lacZ fusions.
      Mutants constructed in the 27 genes showed no major change in response to cell
      wall-acting antibiotics or growth at elevated temperatures nor in alginate
      production. The mutants were examined for their effects on the expression of the
      sigma(22)-dependent promoter of the alginate biosynthetic operon (PalgD) as a
      measure of sigma(22) derepression from MucA. By testing PalgD expression under
      both planktonic and sessile growth conditions, 11 genes were found to play a role
      in the stress response that activates sigma(22). Some mutations caused an
      increase or a decrease in the response to cell wall stress. Interestingly,
      mutations in 7 of the 11 genes caused constitutive PalgD expression under
      nonstressed conditions and thus showed that these genes are involved in
      maintaining envelope homeostasis. Mutations in PA0062 and PA1324 showed
      constitutive PalgD expression during both the planktonic and the sessile modes of
      growth. However, the PA5178 mutation caused constitutive PalgD expression only
      during planktonic growth. In contrast, mutations in PA2717, PA0567, PA3040, and
      PA0920 caused constitutive PalgD expression only in the sessile/biofilm mode of
      growth. This provides evidence that the sigma(22) stimulon for cell envelope
      homeostasis overlaps with biofilm control mechanisms. IMPORTANCE: During chronic
      lung infections, such as in cystic fibrosis patients, Pseudomonas aeruginosa
      produces the exopolysaccharide alginate and forms biofilms that shield the
      organisms from the immune response and increase resistance to antibiotics.
      Activation of alginate genes is under the control of an extracytoplasmic stress
      response system that releases an alternative sigma factor (sigma(22)) in response
      to cell wall stress and then activates expression of a large regulon. In this
      study, a mutant analysis of 27 members of the regulon showed that 11 play a role
      in envelope homeostasis and affect the stress response system itself.
      Interestingly, some genes demonstrate effects only in either the planktonic (free
      swimming) or the sessile (biofilm) mode of growth, which leads to persistence and
      antibiotic tolerance. The studies presented here provide an important initial
      step in dissecting the mechanisms that regulate a critical signal transduction
      pathway that impacts P. aeruginosa pathogenesis.

PMID- 22589291
TI  - Central corneal volume and endothelial cell count following femtosecond laser
      assisted refractive cataract surgery compared to conventional
      phacoemulsification.
AB  - PURPOSE: To compare the effect of conventional phacoemulsification and
      femtosecond laser-assisted cataract surgery on the cornea using Scheimpflug
      imaging and noncontact specular microscopy. METHODS: In each group, 38 eyes (38
      patients) underwent cataract surgery using either femtosecond laser-assisted
      (Alcon LenSx laser) (femtolaser group) or conventional phacoemulsification (phaco
      group). Central corneal thickness, 3-mm corneal volume, and Pentacam Nucleus
      Staging (PNS) were determined by a rotating Scheimpflug camera (Pentacam HR,
      Oculus Optikgerate GmbH), and the volume stress index was calculated at 1 day and
      1 month postoperatively. Endothelial cell count was measured by noncontact
      specular microscopy preoperatively, 1 day, 1 week, and 1 month postoperatively.
      RESULTS: Central corneal thickness was significantly higher in the phaco group
      (607+/-91 MUm) than in the femtolaser group (580+/-42 MUm) on day 1, but did not
      differ significantly preoperatively and at 1 week and 1 month. Volume stress
      index at day 1 was significantly lower in the femtolaser group than in the phaco
      group (P<.05) but did not differ significantly at 1 month. Multivariate
      regression analysis showed that the type of surgery had a significant effect on
      central corneal thickness. CONCLUSIONS: Femtosecond laser-assisted cataract
      surgery causes less corneal swelling in the early postoperative period and may
      cause less trauma to corneal endothelial cells than manual phacoemulsification.

PMID- 22589292
TI  - Refractive and topographic stability of Intacs in eyes with progressive
      keratoconus: five-year follow-up.
AB  - PURPOSE: To evaluate the long-term rate of progression of keratoconus in eyes
      implanted with Intacs (Addition Technology Inc) at 5-year follow-up. METHODS:
      Data of 105 eyes from 85 patients who had undergone consecutive Intacs
      implantation between January 2001 and December 2005 were studied retrospectively
      for progression of keratoconus. Progression of keratoconus was defined as an
      increase in steep keratometry (K) of >= 1.00 diopter (D) over 4 years between 1-
      and 5-year follow-up. All eyes were categorized into three subgroups: eyes with
      documented preoperative progression (change in steep K >= 1.00 D over 12 months
      preoperatively), eyes with documented absence of preoperative progression, and
      eyes with no record of preoperative progression. RESULTS: Ninety-two eyes were
      available for analysis. Overall, 91.3% (84/92) of eyes demonstrated no
      progression between 1- and 5-year follow-up. In the sub-group analysis, 92.9%
      (52/56) of eyes with documented preoperative progression demonstrated no
      progression. Additionally, no statistically significant differences were noted in
      mean steep, flat, and average keratometry; manifest refraction spherical
      equivalent; and uncorrected and corrected distance visual acuity (P>.05) between
      1- and 5-year follow-up. CONCLUSIONS: Results of our study demonstrate the long
      term stability of refractive and topographic outcomes following Intacs
      implantation in eyes with keratoconus. The finding that 92.9% of eyes with
      progressive keratoconus did not progress postoperatively indicates that Intacs
      implantation may be a potential therapeutic option to halt progressive
      keratoconus.

PMID- 22589293
TI  - Phenotype variability in patients carrying KCNJ2 mutations.
AB  - BACKGROUND: Mutations of KCNJ2, the gene encoding the human inward rectifier
      potassium channel Kir2.1, cause Andersen-Tawil syndrome (ATS), a disease
      exhibiting ventricular arrhythmia, periodic paralysis, and dysmorphic features.
      However, some KCNJ2 mutation carriers lack the ATS triad and sometimes share the
      phenotype of catecholaminergic polymorphic ventricular tachycardia (CPVT). We
      investigated clinical and biophysical characteristics of KCNJ2 mutation carriers
      with "atypical ATS." METHODS AND RESULTS: Mutational analyses of KCNJ2 were
      performed in 57 unrelated probands showing typical (>=2 ATS features) and
      atypical (only 1 of the ATS features or CPVT) ATS. We identified 24 mutation
      carriers. Mutation-positive rates were 75% (15/20) in typical ATS, 71% (5/7) in
      cardiac phenotype alone, 100% (2/2) in periodic paralysis, and 7% (2/28) in CPVT.
      We divided all carriers (n=45, including family members) into 2 groups: typical
      ATS (A) (n=21, 47%) and atypical phenotype (B) (n=24, 53%). Patients in (A) had a
      longer QUc interval [(A): 695 +/- 52 versus (B): 643 +/- 35 ms] and higher U-wave
      amplitude (0.24 +/- 0.07 versus 0.18 +/- 0.08 mV). C-terminal mutations were more
      frequent in (A) (85% versus 38%, P<0.05). There were no significant differences
      in incidences of ventricular tachyarrhythmias. Functional analyses of 4 mutations
      found in (B) revealed that R82Q, R82W, and G144D exerted strong dominant negative
      suppression (current reduction by 95%, 97%, and 96%, respectively, versus WT at 
      50 mV) and T305S moderate suppression (reduction by 89%). CONCLUSIONS: KCNJ2 gene
      screening in atypical ATS phenotypes is of clinical importance because more than
      half of mutation carriers express atypical phenotypes, despite their arrhythmia
      severity.

PMID- 22589294
TI  - Prevalence of sequence variants in the RAS-mitogen activated protein kinase
      signaling pathway in pre-adolescent children with hypertrophic cardiomyopathy.
AB  - BACKGROUND: Most cases of apparently idiopathic hypertrophic cardiomyopathy (HCM)
      in children are caused by mutations in cardiac sarcomere protein genes. HCM also
      commonly occurs as an associated feature in some patients with disorders caused
      by mutations in genes encoding components of the RAS-mitogen activated protein
      kinase (MAPK) signaling pathway. Although diagnosis of these disorders is based
      on typical phenotypic features, the dysmorphic manifestations can be subtle and
      therefore overlooked. The aim of this study was to determine the prevalence of
      mutations in RAS-MAPK genes in preadolescent children with idiopathic HCM.
      METHODS AND RESULTS: Seventy-eight patients diagnosed with apparently
      nonsyndromic HCM aged <=13 years underwent clinical and genetic evaluation. The
      entire protein coding sequence of 9 genes implicated in Noonan syndrome and
      related conditions (PTPN11, SOS1, HRAS, KRAS, NRAS, BRAF, RAF1, MAP2K1, and
      MAP2K2), together with CBL (exons 8 and 9) and SHOC2 (4A>G), were screened for
      mutations. Five probands (6.4%) carried novel sequence variants in SOS1 (2
      individuals), BRAF, MAP2K1, and MAP2K2. Structural and molecular data suggest
      that these variants may have functional significance. Nine cardiac sarcomere
      protein genes were screened also; 2 individuals also had mutations in MYBPC.
      CONCLUSIONS: This study reports novel and potentially pathogenic sequence
      variants in genes of the RAS-MAPK pathway, suggesting that genetic lesions
      promoting signaling dysregulation through RAS contribute to disease pathogenesis
      or progression in children with HCM.

PMID- 22589295
TI  - Rupture of the device landing zone during transcatheter aortic valve
      implantation: a life-threatening but treatable complication.
AB  - BACKGROUND: Iatrogenic damage of different structures of the aortic root, in the
      region of the so-called "device landing zone," may occur during transcatheter
      aortic valve implantation (TAVI). It is mostly considered difficult to treat or
      even untreatable. METHODS AND RESULTS: We performed a retrospective analysis of
      the occurrence, clinical presentation, treatment, and outcome of iatrogenic
      rupture in the device landing zone in a series of 618 consecutive patients who
      underwent TAVI at our institution between April 2008 and October 2011. The
      incidence of rupture was 1% (6 patients). The correct diagnosis was established
      during TAVI procedures in 4 and postmortem in 2 patients. The major sign of the
      aortic rupture was apparent bleeding in 4 patients and failure of myocardial
      recovery after valve implantation in 1; it was asymptomatic in 1 patient. The
      iatrogenic rupture in the region of the device landing zone was treated
      surgically in 5 patients and only conservatively in the patient without symptoms.
      When the diagnosis was established correctly during TAVI, only 1 of 4 patients
      died (25%). The overall mortality rate was 50% (3 of 6 patients died).
      CONCLUSIONS: Rupture of different structures in the device landing zone during
      TAVI is a life-threatening complication that can be treated successfully if it is
      immediately recognized and adequately managed.

PMID- 22589296
TI  - Prevalence and the long-term coronary risks of patients with Kawasaki disease in
      a general population <40 years: a national database study.
AB  - BACKGROUND: Patients with Kawasaki disease (kDa) may develop coronary arterial
      lesions and subsequent coronary events. The first reported case in Taiwan was in
      1976, and the annual incidence from 2003 to 2006 was 69/100 000 children < 5
      years. A population study from Taiwan, a country with a high incidence of kDa,
      national health insurance, and easily accessible medical care, would adequately
      reflect the long-term risk. METHODS AND RESULTS: We retrieved the data of kDa
      patients from a national health insurance 2000 to 2010 database of Taiwan, a
      country with a child health index similar to those in the United States. The
      occurrence of coronary complications and interventions was identified by the
      respective International Classification of Diseases, Ninth Revision, codes. The
      prevalence of kDa in the population < 40 years was 34.9/100 000 (male/female
      ratio, 1.47). Coronary complications occurred in 1254 patients (5.37%;
      male/female ratio, 2.19), with an average annual risk of 2.4% (2.7% for males and
      2.0% for females). An acute myocardial infarction occurred in 19 patients (0.08%;
      18 males and 1 female), of whom one third were aged between 10 and 15 years
      (median, 15.7 years; range, 0.7-36.7 years). A coronary intervention was
      performed by catheterization in 18 patients (all males) at a median age of 24.5
      years and by surgery in 10 patients (male/female ratio, 4.0) at a median age of
      21.7 years, with mortality at discharge being 0% and 25%, respectively.
      CONCLUSIONS: This study estimated the overall prevalence of kDa (~1/2940) in a
      population < 40 years. They, particularly the males, carry long-term coronary
      risks from a young age. Risk stratification for a timely coronary intervention
      and risk modification are mandatory.

PMID- 22589297
TI  - Transfer times and outcomes in patients with ST-segment-elevation myocardial
      infarction undergoing interhospital transfer for primary percutaneous coronary
      intervention: APEX-AMI insights.
AB  - BACKGROUND: Transfer delays for primary percutaneous coronary intervention may
      increase mortality in patients with ST-segment-elevation myocardial infarction.
      We examined the association between door 1-to-door 2 (D1D2) time, a measure
      capturing the entire transfer process, and outcomes in patients undergoing
      interhospital transfer for primary percutaneous coronary intervention. METHODS
      AND RESULTS: We evaluated the relationship between D1D2 time and the 90-day
      incidence of death, shock, and heart failure in the subset of 2075 (36.1%) of
      5745 patients who underwent interhospital transfer for primary percutaneous
      coronary intervention in the Assessment of Pexelizumab in Acute Myocardial
      Infarction trial. There was no significant difference in the 90-day incidence of
      death, shock, and heart failure between the transferred and the nontransferred
      groups (10.3% versus 10.2%; P = 0.89). The median difference in symptom-to
      balloon time between the 2 groups was 45 minutes (229 versus 184; P<0.001). The
      primary outcome per 30-minute delay was higher for patients with a D1D2 time
      <=150 minutes (hazard ratio, 1.19: 95% confidence interval, 1.06 to 1.33; P =
      0.004) but not for D1D2 times >150 minutes (hazard ratio, 0.99: 95% confidence
      interval, 0.96 to 1.02; P = 0.496). The association between longer D1D2 time and
      worsening outcome was no longer statistically significant after multivariable
      adjustment. CONCLUSIONS: Longer transfer times were associated with higher rate
      of death, shock, and heart failure among patients undergoing interhospital
      transfer from primary percutaneous coronary intervention, although this
      difference did not persist after adjusting for baseline characteristics.

PMID- 22589299
TI  - Consequences of NMO-IgG binding to aquaporin-4 in neuromyelitis optica.

PMID- 22589298
TI  - Prediction of incident heart failure in general practice: the Atherosclerosis
      Risk in Communities (ARIC) Study.
AB  - BACKGROUND: A simple and effective heart failure (HF) risk score would facilitate
      the primary prevention and early diagnosis of HF in general practice. We examined
      the external validity of existing HF risk scores, optimized a 10-year HF risk
      function, and examined the incremental value of several biomarkers, including N
      terminal pro-brain natriuretic peptide. METHODS AND RESULTS: During 15.5 years
      (210 102 person-years of follow-up), 1487 HF events were recorded among 13 555
      members of the biethnic Atherosclerosis Risk in Communities (ARIC) Study cohort.
      The area under curve from the Framingham-published, Framingham-recalibrated,
      Health ABC HF recalibrated, and ARIC risk scores were 0.610, 0.762, 0.783, and
      0.797, respectively. On addition of N-terminal pro-brain natriuretic peptide, the
      optimism-corrected area under curve of the ARIC HF risk score increased from
      0.773 (95% CI, 0.753-0.787) to 0.805 (95% CI, 0.792-0.820). Inclusion of N
      terminal pro-brain natriuretic peptide improved the overall classification of
      recalibrated Framingham, recalibrated Health ABC, and ARIC risk scores by 18%,
      12%, and 13%, respectively. In contrast, cystatin C or high-sensitivity C
      reactive protein did not add toward incremental risk prediction. CONCLUSIONS: The
      ARIC HF risk score is more parsimonious yet performs slightly better than the
      extant risk scores in predicting 10-year risk of incident HF. The inclusion of N
      terminal pro-brain natriuretic peptide markedly improves HF risk prediction. A
      simplified risk score restricted to a patient's age, race, sex, and N-terminal
      pro-brain natriuretic peptide performs comparably to the full score (area under
      curve, 0.745) and is suitable for automated reporting from laboratory panels and
      electronic medical records.

PMID- 22589300
TI  - Energetics of stalk intermediates in membrane fusion are controlled by lipid
      composition.
AB  - We have used X-ray diffraction on the rhombohedral phospholipid phase to
      reconstruct stalk structures in different pure lipids and lipid mixtures with
      unprecedented resolution, enabling a quantitative analysis of geometry, as well
      as curvature and hydration energies. Electron density isosurfaces are used to
      study shape and curvature properties of the bent lipid monolayers. We observe
      that the stalk structure is highly universal in different lipid systems. The
      associated curvatures change in a subtle, but systematic fashion upon changes in
      lipid composition. In addition, we have studied the hydration interaction prior
      to the transition from the lamellar to the stalk phase. The results indicate that
      facilitating dehydration is the key to promote stalk formation, which becomes
      favorable at an approximately constant interbilayer separation of 9.0 +/- 0.5 A
      for the investigated lipid compositions.

PMID- 22589301
TI  - Amino acid addition to Vibrio cholerae LPS establishes a link between surface
      remodeling in gram-positive and gram-negative bacteria.
AB  - Historically, the O1 El Tor and classical biotypes of Vibrio cholerae have been
      differentiated by their resistance to the antimicrobial peptide polymyxin B.
      However, the molecular mechanisms associated with this phenotypic distinction
      have remained a mystery for 50 y. Both gram-negative and gram-positive bacteria
      modify their cell wall components with amine-containing substituents to reduce
      the net negative charge of the bacterial surface, thereby promoting cationic
      antimicrobial peptide resistance. In the present study, we demonstrate that V.
      cholerae modify the lipid A anchor of LPS with glycine and diglycine residues.
      This previously uncharacterized lipid A modification confers polymyxin resistance
      in V. cholerae El Tor, requiring three V. cholerae proteins: Vc1577 (AlmG),
      Vc1578 (AlmF), and Vc1579 (AlmE). Interestingly, the protein machinery required
      for glycine addition is reminiscent of the gram-positive system responsible for D
      alanylation of teichoic acids. Such machinery was not thought to be used by gram
      negative organisms. V. cholerae O1 El Tor mutants lacking genes involved in
      transferring glycine to LPS showed a 100-fold increase in sensitivity to
      polymyxin B. This work reveals a unique lipid A modification and demonstrates a
      charge-based remodeling strategy shared between gram-positive and gram-negative
      organisms.

PMID- 22589303
TI  - High-throughput, high-fidelity HLA genotyping with deep sequencing.
AB  - Human leukocyte antigen (HLA) genes are the most polymorphic in the human genome.
      They play a pivotal role in the immune response and have been implicated in
      numerous human pathologies, especially autoimmunity and infectious diseases.
      Despite their importance, however, they are rarely characterized comprehensively
      because of the prohibitive cost of standard technologies and the technical
      challenges of accurately discriminating between these highly related genes and
      their many allelles. Here we demonstrate a high-resolution, and cost-effective
      methodology to type HLA genes by sequencing, which combines the advantage of long
      range amplification, the power of high-throughput sequencing platforms, and a
      unique genotyping algorithm. We calibrated our method for HLA-A, -B, -C, and 
      DRB1 genes with both reference cell lines and clinical samples and identified
      several previously undescribed alleles with mismatches, insertions, and
      deletions. We have further demonstrated the utility of this method in a clinical
      setting by typing five clinical samples in an Illumina MiSeq instrument with a 5
      d turnaround. Overall, this technology has the capacity to deliver low-cost, high
      throughput, and accurate HLA typing by multiplexing thousands of samples in a
      single sequencing run, which will enable comprehensive disease-association
      studies with large cohorts. Furthermore, this approach can also be extended to
      include other polymorphic genes.

PMID- 22589302
TI  - Suppression of heat shock protein 27 induces long-term dormancy in human breast
      cancer.
AB  - The mechanisms underlying tumor dormancy have been elusive and not well
      characterized. We recently published an experimental model for the study of human
      tumor dormancy and the role of angiogenesis, and reported that the angiogenic
      switch was preceded by a local increase in VEGF-A and basic fibroblast growth
      factor. In this breast cancer xenograft model (MDA-MB-436 cells), analysis of
      differentially expressed genes revealed that heat shock protein 27 (HSP27) was
      significantly up-regulated in angiogenic cells compared with nonangiogenic cells.
      The effect of HSP27 down-regulation was further evaluated in cell lines, mouse
      models, and clinical datasets of human patients with breast cancer and melanoma.
      Stable down-regulation of HSP27 in angiogenic tumor cells was followed by long
      term tumor dormancy in vivo. Strikingly, only 4 of 30 HSP27 knockdown xenograft
      tumors initiated rapid growth after day 70, in correlation with a regain of HSP27
      protein expression. Significantly, no tumors escaped from dormancy without HSP27
      expression. Down-regulation of HSP27 was associated with reduced endothelial cell
      proliferation and decreased secretion of VEGF-A, VEGF-C, and basic fibroblast
      growth factor. Conversely, overexpression of HSP27 in nonangiogenic cells
      resulted in expansive tumor growth in vivo. By clinical validation, strong HSP27
      protein expression was associated with markers of aggressive tumors and decreased
      survival in patients with breast cancer and melanoma. An HSP27-associated gene
      expression signature was related to molecular subgroups and survival in breast
      cancer. Our findings suggest a role for HSP27 in the balance between tumor
      dormancy and tumor progression, mediated by tumor-vascular interactions.
      Targeting HSP27 might offer a useful strategy in cancer treatment.

PMID- 22589304
TI  - Alterations in RNA processing during immune-mediated programmed cell death.
AB  - During immune-mediated death, death-inducing granzyme (Gzm) proteases concentrate
      in the nucleus of cells targeted for immune elimination, suggesting that nuclear
      processes are important targets. Here we used differential 2D proteomics of GzmA
      treated nuclei to identify potential GzmA substrates. Of 44 candidates, 33 were
      RNA-binding proteins important in posttranscriptional RNA processing, including
      14 heterogeneous nuclear ribonucleoproteins (hnRNP). Multiple hnRNPs were
      degraded in cells undergoing GzmA-, GzmB-, or caspase-mediated death. GzmA and
      caspase activation impaired nuclear export of newly synthesized RNA and disrupted
      pre-mRNA splicing. Expressing GzmA-resistant hnRNP A1 inhibited GzmA-mediated
      cell death and rescued pre-mRNA splicing, suggesting that hnRNP A1 is an
      important GzmA substrate. Cellular stresses are known to inhibit initiation of
      cap-dependent translation. Disrupting pre-mRNA processing should block further
      new protein synthesis and promote death by interfering with pathways induced to
      protect cells from death.

PMID- 22589306
TI  - Health disparities in asthma.

PMID- 22589305
TI  - Heterotrimer-independent regulation of activation-loop phosphorylation of Snf1
      protein kinase involves two protein phosphatases.
AB  - The SNF1/AMP-activated protein kinases are alphabetagamma-heterotrimers that
      sense and regulate energy status in eukaryotes. They are activated by
      phosphorylation of the catalytic Snf1/alpha subunit, and the Snf4/gamma
      regulatory subunit regulates phosphorylation through adenine nucleotide binding.
      In Saccharomyces cerevisiae, the Snf1 subunit is phosphorylated on the activation
      loop Thr-210 in response to glucose limitation. To assess the requirement of the
      heterotrimer for regulated Thr-210 phosphorylation, we examined Snf1 and a
      truncated Snf1 kinase domain (residues 1-309) that has partial Snf1 function.
      Snf1(1-309) does not interact with the beta and Snf4/gamma regulatory subunits,
      and its activity was independent of them in vivo. Phosphorylation of both Snf1
      and Snf1(1-309) increased in response to glucose limitation in wild-type cells
      and in cells lacking beta- and Snf4/gamma-subunits. These results indicate that
      glucose regulation of activation-loop phosphorylation can occur by mechanism(s)
      that function independently of the regulatory subunits. We further show that the
      Reg1-Glc7 protein phosphatase 1 and Sit4 type 2A-like phosphatase are largely
      responsible for dephosphorylation of Thr-210 of Snf1(1-309). Together, these
      findings suggest that these two phosphatases mediate heterotrimer-independent
      regulation of Thr-210 phosphorylation.

PMID- 22589307
TI  - More muscle in asthma, but where did it come from?

PMID- 22589308
TI  - The microbiota in respiratory disease.

PMID- 22589309
TI  - Mortality and denial of admission to an intensive care unit.

PMID- 22589310
TI  - Control of fever in septic shock: should we care or intervene?

PMID- 22589311
TI  - Behind the mask: overdue evidence.

PMID- 22589312
TI  - An official multi-society statement: the role of clinical research results in the
      practice of critical care medicine.
AB  - BACKGROUND: While the results of clinical research are clearly valuable in the
      care of critically ill patients, the limitations of such information and the role
      of other forms of medical knowledge for clinical decision making have not been
      carefully examined. METHODS: The leadership of three large professional societies
      representing critical care practitioners convened a diverse group representing a
      wide variety of views regarding the role of clinical research results in clinical
      practice to develop a document to serve as a basis for agreement and a framework
      for ongoing discussion. RESULTS: Consensus was reached on several issues. While
      the results of rigorous clinical research are important in arriving at the best
      course of action for an individual critically ill patient, other forms of medical
      knowledge, including clinical experience and pathophysiologic reasoning, remain
      essential. No single source of knowledge is sufficient to guide clinical
      decisions, nor does one kind of knowledge always take precedence over others.
      Clinicians will find clinical research compelling for a variety of reasons that
      go beyond study design. While clinical practice guidelines and protocols based
      upon clinical research may improve care and decrease variability in practice,
      clinicians must be able to understand and articulate the rationale as to why a
      particular protocol or guideline is used or why an alternative approach is taken.
      Making this clinical reasoning explicit is necessary to understand practice
      variability. CONCLUSIONS: Understanding the strengths and weaknesses of different
      kinds of medical knowledge for clinical decision making and factors beyond study
      design that make clinical research compelling to clinicians can provide a
      framework for understanding the role of clinical research in practice.

PMID- 22589313
TI  - Cord-blood vitamin d levels and risk of recurrent wheezing, effect of sleep
      disordered breathing on blood pressure in children, and long-term impact of
      bronchopulmonary dysplasia.

PMID- 22589314
TI  - An unusual cause of air-fluid levels in the chest.

PMID- 22589315
TI  - Lung cancer is more common in early GOLD stages of COPD: a spurious association?

PMID- 22589316
TI  - Transparent reporting of all GRADE criteria in clinical practice guidelines.

PMID- 22589317
TI  - Dynamic changes in the expression of neutrophil extracellular traps in acute
      respiratory infections.

PMID- 22589318
TI  - Arsenic and lung cancer in never-smokers: lessons from Chile.

PMID- 22589319
TI  - A symptom and its etiology.

PMID- 22589320
TI  - Positive predictive value of BI-RADS MR imaging.
AB  - PURPOSE: To evaluate the positive predictive values (PPVs) of Breast Imaging and
      Reporting Data Systems (BI-RADS) assessment categories for breast magnetic
      resonance (MR) imaging and to identify the BI-RADS MR imaging lesion features
      most predictive of cancer. MATERIALS AND METHODS: This institutional review board
      approved HIPAA-compliant prospective multicenter study was performed with written
      informed consent. Breast MR imaging studies of the contralateral breast in women
      with a recent diagnosis of breast cancer were prospectively evaluated.
      Contralateral breast MR imaging BI-RADS assessment categories, morphologic
      descriptors for foci, masses, non-masslike enhancement (NMLE), and kinetic
      features were assessed for predictive values for malignancy. PPV of each imaging
      characteristic of interest was estimated, and logistic regression analysis was
      used to examine the predictive ability of combinations of characteristics.
      RESULTS: Of 969 participants, 71.3% had a BI-RADS category 1 or 2 assessment;
      10.9%, a BI-RADS category 3 assessment; 10.0%, a BI-RADS category 4 or 5
      assessment; and 7.7%, a BI-RADS category 0 assessment on the basis of initial MR
      images. Thirty-one cancers were detected with MR imaging. Overall PPV for BI-RADS
      category 4 and 5 lesions was 0.278, with 17 cancers in patients with a BI-RADS
      category 4 lesion (PPV, 0.205) and 10 cancers in patients with a BI-RADS category
      5 lesion (PPV, 0.714). Of the cancers, one was a focus, 17 were masses, and 13
      were NMLEs. For masses, irregular shape, irregular margins, spiculated margins,
      and marked internal enhancement were most predictive of malignancy. For NMLEs,
      ductal, clumped, and reticular or dendritic enhancement were the features most
      frequently seen with malignancy. Kinetic enhancement features were less
      predictive of malignancy than were morphologic features. CONCLUSION: Standardized
      terminology of the BI-RADS lexicon enables quantification of the likelihood of
      malignancy for MR imaging-detected lesions through careful evaluation of lesion
      features. In particular, BI-RADS assessment categories and morphologic
      descriptors for masses and NMLE were useful in estimating the probability of
      cancer.

PMID- 22589321
TI  - Evaluation of abdominal aortic aneurysm after endovascular repair: prospective
      validation of contrast-enhanced US with a second-generation US contrast agent.
AB  - PURPOSE: To prospectively assess the accuracy of contrast agent-enhanced (CE)
      ultrasonography (US) with a second-generation US contrast agent in the detection
      and classification of endoleaks after endovascular repair of abdominal aortic
      aneurysms (EVAR), with computed tomographic (CT) angiography as the reference
      standard. MATERIALS AND METHODS: Institutional review board and written informed
      consent were obtained. Thirty-five patients who underwent EVAR were enrolled in a
      prospective study that consisted of CT angiography and CE US studies performed at
      1- and 6-month follow-up and performed yearly thereafter. CE US was performed
      after bolus injection of 2.4 mL of sulfur hexafluoride by using equipment with
      specific software for contrast studies. Angiography was performed in patients who
      had type II endoleaks with an increase in aneurysm sac size and in patients with
      type I or III endoleaks. CE US sensitivity, specificity, positive and negative
      predictive values, and accuracy were determined for endoleak detection, and Cohen
      kappa statistic was used to assess agreement of CE US and CT angiographic
      findings for endoleak classification. RESULTS: A total of 126 CT angiographic and
      CE US studies were performed. CT angiography depicted 34 endoleaks in 16 patients
      (type IA, n=1; type IB, n=1; type II inferior mesenteric artery, n=2; type II
      lumbar artery, n=28; type II complex, inferior mesenteric, and lumbar arteries,
      n=2). CE US depicted 33 endoleaks. Sensitivity, specificity, positive predictive
      value, negative predictive value, and accuracy of CE US in endoleak detection
      were 97%, 100%, 100%, 98%, and 99%, respectively. CE US enabled correct
      classification of 26 of 33 endoleaks. No clinically important endoleak was missed
      at CE US. CONCLUSION: CE US yields good sensitivity, specificity, and accuracy in
      endoleak detection, and it might represent a noninvasive tool that can be used in
      the follow-up of patients who undergo EVAR.

PMID- 22589322
TI  - Dual inversion-recovery mr imaging sequence for reduced blood signal on late
      gadolinium-enhanced images of myocardial scar.
AB  - PURPOSE: To investigate whether a dual inversion-recovery (IR) prepulse improves
      scar-to-blood contrast and expert confidence and consistency at late gadolinium
      enhanced magnetic resonance (MR) imaging of myocardial scar compared with the
      standard IR technique at 3.0 T. MATERIALS AND METHODS: The study was approved by
      the local ethics committee, and all patients provided written informed consent.
      Twelve men (mean age+/-standard deviation, 63 years+/-8) with known myocardial
      scar underwent MR imaging 10, 20, and 30 minutes after administration of 0.2
      mmol/kg gadobutrol with a standard and dual IR sequence. Contrast-to-noise ratios
      (CNRs) were measured by using region-of-interest analysis, and data were compared
      with the analysis of variance test. Two experts measured scar size and
      transmurality, and data were compared with the Student t test and Bland-Altman
      test. Experts assigned confidence scores for scar detection and transmurality,
      which were compared with a Wilcoxon matched-pairs signed rank test. RESULTS:
      Patient data showed improved scar-to-blood CNR for the dual IR technique compared
      with the standard IR technique at all time points (P<.05). For images obtained 20
      minutes after contrast material administration, the dual IR sequence provided
      higher confidence scores for scar detection and transmurality assessment (P<.05)
      and resulted in more consistent assessment of scar size and transmurality between
      readers compared with the IR sequence (P<.05). CONCLUSION: In this preliminary
      patient study, the dual IR prepulse improved contrast, scar visualization, and
      expert confidence and reduced expert differences in transmurality and scar size
      assessment compared with the standard IR technique.

PMID- 22589323
TI  - Subjective quality of vision.

PMID- 22589324
TI  - IOL scaffold technique for posterior capsule rupture.

PMID- 22589325
TI  - Femtosecond laser-assisted LASIK improves quality of life.
AB  - PURPOSE: To investigate the quality of life (QOL) outcomes of femtosecond laser
      assisted LASIK using the Quality of Life Impact of Refractive Correction (QIRC)
      questionnaire. METHODS: Translation of the QIRC questionnaire from English to
      Greek followed standard international protocols. The questionnaire was completed
      by 190 individuals, aged 18 to 39 years with myopia (range: -0.75 to -8.50
      diopters) and corrected distance visual acuity (CDVA) of logMAR 0.2 or better
      (Snellen equivalent 20/32) in the worse eye. Half of this sample underwent LASIK
      with femtosecond laser flap creation and ablation with the Visx Star S4 IR
      excimer laser (Abbott Medical Optics). The questionnaire was scored with Rasch
      analysis. Validity was tested by internal consistency reliability (Cronbach's
      alpha) and repeatability by intraclass correlation coefficient (ICC) and Bland
      Altman limits of agreement, convergent validity was examined with inter-item
      correlations, and construct validity was evaluated by known groups comparison
      analysis. RESULTS: The total QIRC score improved with femtosecond laser-assisted
      LASIK from mean 38.9+/-5.7 preoperatively to 53.7+/-5.1 postoperatively (P<.001).
      Among the pre-treatment and control groups, QIRC score was greater for those
      wearing contact lenses than those wearing spectacles (P<.01). The Greek version
      of the QIRC had good internal consistency reliability. Inter-item correlations
      were all significant (P<.001), ranging from 0.32 to 0.79. Repeatability was high
      (Bland-Altman limits of agreement were -6.72 to +5.41 and ICC for the total score
      was 0.98). CONCLUSIONS: Femtosecond laser-assisted LASIK leads to marked
      improvements in refractive error-related quality of life. This study also
      provides evidence for the reliability and validity of the Greek version of the
      QIRC questionnaire.

PMID- 22589326
TI  - An efficient method for transient gene expression in monocots applied to modify
      the Brachypodium distachyon cell wall.
AB  - BACKGROUND: Agrobacterium-mediated transformation is widely used to produce
      insertions into plant genomes. There are a number of well-developed Agrobacterium
      mediated transformation methods for dicotyledonous plants, but there are few for
      monocotyledonous plants. METHODS: Three hydrolase genes were transiently
      expressed in Brachypodium distachyon plants using specially designed vectors that
      express the gene product of interest and target it to the plant cell wall.
      Expression of functional hydrolases in genotyped plants was confirmed using
      western blotting, activity assays, cell wall compositional analysis and
      digestibility tests. KEY RESULTS: An efficient, new, Agrobacterium-mediated
      approach was developed for transient gene expression in the grass B. distachyon,
      using co-cultivation of mature seeds with bacterial cells. This method allows
      transformed tissues to be obtained rapidly, within 3-4 weeks after co
      cultivation. Also, the plants carried transgenic tissue and maintained transgenic
      protein expression throughout plant maturation. The efficiency of transformation
      was estimated at around 5 % of initially co-cultivated seeds. Application of this
      approach to express three Aspergillus nidulans hydrolases in the Brachypodium
      cell wall successfully confirmed its utility and resulted in the expected
      expression of active microbial proteins and alterations of cell wall composition.
      Cell wall modifications caused by expression of A. nidulans alpha
      arabinofuranosidase and alpha-galactosidase increased the biodegradability of
      plant biomass. CONCLUSIONS: This newly developed approach is a quick and
      efficient technique for expressing genes of interest in Brachypodium plants,
      which express the gene product throughout development. In the future, this could
      be used for broad functional genomics studies of monocots and for
      biotechnological applications, such as plant biomass modification for biofuel
      production.

PMID- 22589327
TI  - Modelling fungal sink competitiveness with grains for assimilates in wheat
      infected by a biotrophic pathogen.
AB  - BACKGROUND AND AIMS: Experiments have shown that biotrophic fungi divert
      assimilates for their growth. However, no attempt has been made either to account
      for this additional sink or to predict to what extent it competes with both grain
      filling and plant reserve metabolism for carbon. Fungal sink competitiveness with
      grains was quantified by a mixed experimental-modelling approach based on winter
      wheat infected by Puccinia triticina. METHODS: One week after anthesis, plants
      grown under controlled conditions were inoculated with varying loads. Sporulation
      was recorded while plants underwent varying degrees of shading, ensuring a range
      of both fungal sink and host source levels. Inoculation load significantly
      increased both sporulating area and rate. Shading significantly affected net
      assimilation, reserve mobilization and sporulating area, but not grain filling or
      sporulation rates. An existing carbon partitioning (source-sink) model for wheat
      during the grain filling period was then enhanced, in which two parameters
      characterize every sink: carriage capacity and substrate affinity. Fungal sink
      competitiveness with host sources and sinks was modelled by representing spore
      production as another sink in diseased wheat during grain filling. KEY RESULTS:
      Data from the experiment were fitted to the model to provide the fungal sink
      parameters. Fungal carriage capacity was 0.56 +/- 0.01 ug dry matter  degrees Cd(
      1) per lesion, much less than grain filling capacity, even in highly infected
      plants; however, fungal sporulation had a competitive priority for assimilates
      over grain filling. Simulation with virtual crops accounted for the importance of
      the relative contribution of photosynthesis loss, anticipated reserve depletion
      and spore production when light level and disease severity vary. The grain
      filling rate was less reduced than photosynthesis; however, over the long term,
      yield loss could double because the earlier reserve depletion observed here would
      shorten the duration of grain filling. CONCLUSIONS: Source-sink modelling holds
      the promise of accounting for plant-pathogen interactions over time under
      fluctuating climatic/lighting conditions in a robust way.

PMID- 22589328
TI  - A functional trait perspective on plant invasion.
AB  - BACKGROUND AND AIMS: Global environmental change will affect non-native plant
      invasions, with profound potential impacts on native plant populations,
      communities and ecosystems. In this context, we review plant functional traits,
      particularly those that drive invader abundance (invasiveness) and impacts, as
      well as the integration of these traits across multiple ecological scales, and as
      a basis for restoration and management. SCOPE: We review the concepts and
      terminology surrounding functional traits and how functional traits influence
      processes at the individual level. We explore how phenotypic plasticity may lead
      to rapid evolution of novel traits facilitating invasiveness in changing
      environments and then 'scale up' to evaluate the relative importance of
      demographic traits and their links to invasion rates. We then suggest a
      functional trait framework for assessing per capita effects and, ultimately,
      impacts of invasive plants on plant communities and ecosystems. Lastly, we focus
      on the role of functional trait-based approaches in invasive species management
      and restoration in the context of rapid, global environmental change.
      CONCLUSIONS: To understand how the abundance and impacts of invasive plants will
      respond to rapid environmental changes it is essential to link trait-based
      responses of invaders to changes in community and ecosystem properties. To do so
      requires a comprehensive effort that considers dynamic environmental controls and
      a targeted approach to understand key functional traits driving both invader
      abundance and impacts. If we are to predict future invasions, manage those at
      hand and use restoration technology to mitigate invasive species impacts, future
      research must focus on functional traits that promote invasiveness and invader
      impacts under changing conditions, and integrate major factors driving invasions
      from individual to ecosystem levels.

PMID- 22589329
TI  - Co-ordinated development of the leaf midrib xylem with the lamina in Nicotiana
      tabacum.
AB  - BACKGROUND AND AIMS: The water-transport capacity of leaf venation is positively
      related to the leaf-lamina area, because the number and diameter of vein-xylem
      conduits are controlled to match the lamina area. This study aimed to investigate
      how this co-ordinated relationship between the leaf-lamina area and vein-xylem
      characteristics is achieved by examining the midrib xylem of tobacco leaves.
      METHODS: The changes in the midrib-xylem characteristics over time were
      quantified using leaves with four different final lamina areas. The measured data
      were fitted to sigmoidal functions. From the constants of the fitted curves, the
      final values in mature leaves, maximal developmental rates (V(Dev)) and
      developmental duration (T(Dev)) were estimated for each of the xylem
      characteristics. Whether it is the lamina or the midrib xylem that drives the co
      ordinated development was examined by lamina removal from unfolding leaves. The
      effects of the application of 0.1 % IAA (indole-3-acetic acid) to leaves with the
      laminas removed were also analysed. KEY RESULTS: For both the leaf lamina and the
      midrib-xylem characteristics, the differences in final values among leaves with
      different lamina areas were more strongly associated with those in V(Dev).
      Notably, the V(Dev) values of the midrib-xylem characteristics were related to
      those of the leaf-lamina area. By lamina removal, the conduit diameter was
      reduced but the number of conduits did not significantly change. By IAA
      application, the decrease in the conduit diameter was halted, and the number of
      conduits in the midrib xylem increased. CONCLUSIONS: According to the results,
      the V(Dev) values of the lamina area and the midrib-xylem characteristics changed
      in a co-ordinated manner, so that the water-transport capacity of the midrib
      xylem was positively related to the leaf-lamina area. The results also suggest
      that IAA derived from the leaf lamina plays a crucial role in the development of
      the leaf venation.

PMID- 22589330
TI  - Anti-MDA5 antibody, ferritin and IL-18 are useful for the evaluation of response
      to treatment in interstitial lung disease with anti-MDA5 antibody-positive
      dermatomyositis.
AB  - OBJECTIVE: The aim of this study was to investigate the precise clinical
      characteristics and to analyse the association between the anti-MDA5 antibody
      (anti-MDA5ab) titre and disease status in patients with anti-MDA5ab-positive DM.
      METHODS: Twenty-seven patients who presented with DM and were positive for the
      anti-MDA5ab were enrolled. The association between the clinical manifestations
      and the clinical parameters, including the anti-MDA5ab, was analysed. RESULTS:
      The complication of rapidly progressive interstitial lung disease (RP-ILD)
      occurred in 20 (74%) patients. The frequencies of fatal outcome, relapse and
      malignancy were 33, 4 and 4%, respectively. Remarkably, a fatal outcome occurred
      within the first 6 months. Compared with six non-RP-ILD patients, elderly age at
      onset, severely involved pulmonary function and high levels of serum ferritin
      were present in 20 RP-ILD patients with anti-MDA5ab. Alveolar-arterial oxygen
      difference (AaDO(2)) >=32 mmHg and ferritin >=828 ng/ml at admission were poor
      prognostic factors in RP-ILD patients with anti-MDA5ab-positive DM. The median
      value of the anti-MDA5ab titre on admission was higher in patients who later died
      than in those who survived. The efficacy of treatment was indicated by the anti
      MDA5ab, ferritin and IL-18 concentrations. The decline index of the anti-MDA5ab
      titre after treatment was lower in the subset of patients who died than in the
      subset of patients who lived. Sustained high levels of anti-MDA5ab, ferritin and
      IL-18 were present in the patients who died. CONCLUSION: Anti-MDA5ab titre and
      ferritin and IL-18 concentrations are useful for the evaluation of the response
      to treatment and the status of ILD in patients with anti-MAD5ab-positive DM.

PMID- 22589331
TI  - Gastric ulcer and gastroenteritis caused by Epstein-Barr virus during
      immunosuppressive therapy for a child with systemic juvenile idiopathic
      arthritis.

PMID- 22589332
TI  - Lacrimal drainage obstruction in gastric cancer patients receiving S-1
      chemotherapy.
AB  - BACKGROUND: This study was conducted to determine the incidence and clinical
      characteristics of lacrimal drainage obstruction (LDO) in patients receiving S-1
      chemotherapy. PATIENTS AND METHODS: Consecutive 170 patients with gastric cancer
      who underwent curative surgery and received adjuvant S-1 chemotherapy were
      enrolled. S-1 was administered orally (40 mg/m2 b.i.d. on days 1-28 every 6
      weeks) for 1 year. Ophthalmologic examinations were carried out on patients
      complaining of epiphora. RESULTS: Thirty-one patients (18%) developed epiphora.
      Among 31 patients, 25 underwent ophthalmologic examinations and 22 (88%) were
      diagnosed with LDO. The median time to the onset of LDO was 2.9 months. The most
      common site of obstruction was the nasolacrimal duct [86% (19/22)]; punctal [23%
      (5/22)] and canalicular obstruction [14% (3/22)] were also noted. In multivariate
      analysis, total gastrectomy [versus partial gastrectomy: hazard ratio (HR), 2.9;
      P=0.014] and creatinine clearance<50 ml/min (versus >=50 ml/min: HR, 2.9;
      P=0.038) were independent risk factors for the development of LDO. CONCLUSION:
      Considering the high incidence of LDO in patients receiving S-1 chemotherapy,
      oncologists should be alert to epiphora and cooperate with ophthalmologists in
      the early stages to improve the quality of life of patients and avoid more
      complicated ophthalmologic procedures.

PMID- 22589333
TI  - A cellular response linking eIF4AI activity to eIF4AII transcription.
AB  - The recruitment of ribosomes to eukaryotic cellular mRNAs requires the activity
      of two prototypic RNA helicases, eukaryotic initiation factor (eIF) 4AI and
      eIF4AII. The eIF4A isoforms are highly conserved, are thought to be functionally
      interchangeable, and are directed to the 5' m(7)GpppN cap structure of mRNAs
      during translation initiation by virtue of their assembly into eIF4F, a
      heterotrimeric complex that also harbors the eIF4E cap binding protein and eIF4G
      scaffolding unit. During the course of RNA interference experiments aimed at
      investigating the respective roles of eIF4AI and eIF4AII in translation, we
      uncovered a cellular response pathway whereby suppression of eIF4AI increases
      transcription of the eIF4AII gene, leading to elevated eIF4AII mRNA and protein
      levels. Inhibition of eIF4AI suppresses protein synthesis, and although eIF4AII
      protein levels increase above and beyond what should be sufficient to compensate
      for the decrease in eIF4AI levels, there is no corresponding rescue of
      translation or of the block on cellular proliferation that occurs upon eIF4AI
      suppression. These results were phenocopied using the small molecule eIF4A
      inhibitor hippuristanol. Taken together, our results indicate that eIF4AI and
      eIF4AII expression appear linked and that the two protein isoforms exhibit
      functional differences.

PMID- 22589335
TI  - Enhanced depth imaging optical coherence tomography: choroidal thickness and
      correlations with age, refractive error, and axial length.
AB  - BACKGROUND AND OBJECTIVE: To evaluate choroidal thickness at five macular
      locations and assess the correlations between choroidal thickness at these
      locations with age, refractive error, and axial length. PATIENTS AND METHODS:
      Eighty-four eyes from 42 healthy adult volunteers were included. Enhanced depth
      imaging by spectral-domain optical coherence tomography was performed, and
      choroidal thickness was measured at five macular locations: subfoveal and 3 mm
      nasal, temporal, superior, and inferior. Correlations of choroidal thickness at
      each location with age, refractive error, and axial length were analyzed.
      RESULTS: Mean choroidal thicknesses at the subfoveal, superior, inferior,
      temporal, and nasal locations were 293, 308, 264, 263, and 174 MUm, respectively.
      A correlation was found between choroidal thickness, age, refractive error, and
      axial length at all locations. CONCLUSION: Mean subfoveal choroidal thickness in
      healthy adults is approximately 300 MUm. A correlation was found between
      choroidal thickness and all parameters studied.

PMID- 22589334
TI  - Affinity resins containing enzymatically resistant mRNA cap analogs--a new tool
      for the analysis of cap-binding proteins.
AB  - Cap-binding proteins have been routinely isolated using m7GTP-Sepharose; however,
      this resin is inefficient for proteins such as DcpS (scavenger decapping enzyme),
      which interacts not only with the 7-methylguanosine, but also with the second cap
      base. In addition, DcpS purification may be hindered by the reduced resin
      capacity due to the ability of DcpS to hydrolyze m7GTP. Here, we report the
      synthesis of new affinity resins, m7GpCH2pp- and m7GpCH2ppA-Sepharoses, with
      attached cap analogs resistant to hydrolysis by DcpS. Biochemical tests showed
      that these matrices, as well as a hydrolyzable m7GpppA-Sepharose, bind
      recombinant mouse eIF4E28-217 specifically and at high capacity. In addition,
      purification of cap-binding proteins from yeast extracts confirmed the presence
      of all expected cap-binding proteins, including DcpS in the case of m7GpCH2pp-
      and m7GpCH2ppA-Sepharoses. In contrast, binding studies in vitro demonstrated
      that recombinant human DcpS efficiently bound only m7GpCH2ppA-Sepharose. Our data
      prove the applicability of these novel resins, especially m7GpCH2ppA-Sepharose,
      in biochemical studies such as the isolation and identification of cap-binding
      proteins from different organisms.

PMID- 22589336
TI  - Revisiting autologous platelets as an adjuvant in macular hole repair: chronic
      macular holes without prone positioning.
AB  - BACKGROUND AND OBJECTIVE: Chronic macular hole and inability to maintain prone
      positioning remain poor prognostic markers for successful macular hole closure.
      The authors revisited the role of autologous platelets as an adjunct to internal
      limiting membrane (ILM) peeling of chronic macular holes in patients unable to
      maintain prone positioning. PATIENTS AND METHODS: A retrospective case study was
      conducted on 13 eyes of 13 patients with full-thickness chronic macular hole (>
      24 months). Each patient was unable to maintain prone positioning due to medical
      and physical comorbidities. Each eye was treated with pars plana vitrectomy, ILM
      peeling, autologous platelets, and C(3)F(8) gas tamponade. No positioning was
      advised postoperatively. All patients had complete ophthalmic examinations
      preoperatively and 1 day and 1, 3, and 6 months postoperatively with optical
      coherence tomography. Outcome measures were anatomic closure based on Tornambe
      classification, final best-corrected visual acuity, and improvement of quality of
      vision. RESULTS: All 13 patients completed 6 months' follow-up. Macular hole
      duration ranged from 2 to 5 years. There was a 100% macular hole closure rate at
      1 and 6 months postoperatively. All patients reported subjective improvement in
      visual acuity as an improvement of an absolute central scotoma. At 6 months
      postoperatively, 38% of patients reported improved best-corrected visual acuity.
      There were no recurrences. CONCLUSION: Autologous platelets and ILM peeling may
      function synergistically to enhance chronic macular hole closure in patients
      unable to maintain prone positioning.

PMID- 22589337
TI  - Clinical results of the Neusidl Corneal Inserter((r)), a new donor inserter for
      Descemet's stripping automated endothelial keratoplasty, for small Asian eyes.
AB  - BACKGROUND AND OBJECTIVE: To present the clinical outcomes of the Neusidl Corneal
      Inserter (NCI) (Fischer Surgical, Imperial, MO), a new donor inserter for
      Descemet's stripping automated endothelial keratoplasty (DSAEK). PATIENTS AND
      METHODS: Six eyes of 6 Japanese patients (mean age = 74.0 years) with endothelial
      dysfunction were enrolled in this prospective, non-comparative study. All
      patients had a small cornea of 9.0 mm or less in diameter. A donor was inserted
      into the eye using NCI. Intraoperative and postoperative complications,
      postoperative donor endothelial cell densities (ECD), and best-corrected visual
      acuity (BCVA) were evaluated. RESULTS: Donor loading onto NCI was successful in
      all cases. No intraoperative or postoperative complications were noted. All cases
      reached more than 20/63 BCVA within 12 months. Mean ECD was 2,441 cells/mm(2)
      (mean loss = 22.1%) at 6 months and 2,159 cells/mm(2) (mean loss = 31.0%) at 12
      months. CONCLUSION: Graft insertion with NCI is safe in DSAEK with low
      endothelial cell loss.

PMID- 22589338
TI  - Therapeutic window of retinal photocoagulation with green (532-nm) and yellow
      (577-nm) lasers.
AB  - BACKGROUND AND OBJECTIVE: The 577-nm (yellow) laser provides an alternative to
      the 532-nm (green) laser in retinal photocoagulation, with potential benefits in
      macular treatment and through ocular opacities. To assess relative risk of
      thermomechanical rupture of Bruch's membrane with yellow laser in
      photocoagulation, the therapeutic window, the ratio of threshold powers for mild
      coagulation and rupture, was measured. MATERIALS AND METHODS: Retinal coagulation
      and rupture thresholds, visualized ophthalmoscopically, were measured with 577-
      and 532-nm lasers using 10- to 100-ms pulses in 34 rabbit eyes. Lesions at 1 and
      7 days were assessed histologically. RESULTS: Coagulation threshold with yellow
      laser was 26% lower than with green laser. The therapeutic window increased
      linearly with log-duration for both wavelengths with a difference in parallel
      slope intercept of 0.36 +/- 0.20, corresponding to 8% to 15% wider therapeutic
      window for yellow wavelength. CONCLUSION: The therapeutic window of retinal
      photocoagulation in rabbits at 577 nm is slightly wider than at 532 nm, whereas
      histologically the lesions are similar.

PMID- 22589339
TI  - eComment. Activated recombinant factor VII in intractable bleeding after cardiac
      surgery.

PMID- 22589340
TI  - eComment. An oval-shaped unidirectional check-valved patch for treating
      ventricular septal defects.

PMID- 22589341
TI  - eComment. Ventricular septal defect correction in patients with severe pulmonary
      hypertension.

PMID- 22589342
TI  - eComment. Unidirectional flap valve patch closure of ventricular septal defects.

PMID- 22589343
TI  - eComment. Re: Re-exploration for bleeding or tamponade after cardiac operation.

PMID- 22589344
TI  - eComment. Postoperative bleeding without re-exploration may increase operative
      mortality.

PMID- 22589345
TI  - eComment. Postoperative bleeding in cardiac surgery: the issue is not resolved
      yet.

PMID- 22589346
TI  - eComment. Nurse-led clinics and cost-effectiveness.

PMID- 22589347
TI  - eComment. Re: Radiological patterns of primary graft dysfunction after lung
      transplantation.

PMID- 22589348
TI  - eComment. Pectus excavatum: the surgical opinion.

PMID- 22589349
TI  - eComment. Oesophagectomy: Could the anastomotic location be an independent
      prognostic factor?

PMID- 22589350
TI  - eComment. "Electric" Cox-maze IV with bipolar radiofrequency: toward full
      transmurality.

PMID- 22589351
TI  - eComment. Coronary artery bypass grafting in left ventricle dysfunction.

PMID- 22589352
TI  - eComment. The patch and glue technique with or without TachoSil?

PMID- 22589353
TI  - eComment. Acute aortic dissection type A: which strategy of the arterial
      perfusion to choose?

PMID- 22589354
TI  - eComment. Right atrioventricular valve with congenitally absent cusp.

PMID- 22589355
TI  - eComment. Two-stage repair of Ebstein's anormaly in a neonate.

PMID- 22589357
TI  - Retracted: A 5-year clinical experience with bipolar radiofrequency ablation for
      permanent atrial fibrillation concomitant to coronary artery bypass grafting and
      aortic valve surgery [Interact CardioVasc Thorac Surg 2008;7:777-80].

PMID- 22589356
TI  - eComment. Mitral and aortic valve endocarditis caused by Streptococcus
      constellatus.

PMID- 22589358
TI  - Dramatic regression of amelanotic choroidal melanoma with PDT following poor
      response to brachytherapy.
AB  - Photodynamic therapy (PDT) has been used for treatment of choroidal neovascular
      membrane from exudative macular degeneration. Other applications include
      treatment of some intraocular tumors, such as choroidal hemangioma,
      vasoproliferative tumor, and choroidal osteoma. The authors report the effect of
      PDT for amelanotic choroidal melanoma. A 40-year-old woman with an amelanotic
      choroidal melanoma of 6.5 mm thickness showed poor response to iodine
      brachytherapy (80 Gy apical dose) with no reduction in thickness at 16 months of
      follow-up. There was prominent residual tumor. The amelanotic tumor was treated
      with verteporfin PDT using three overlapping spots (8,600 microns), with
      avoidance of the optic disc using standard treatment parameters. Dramatic tumor
      regression over 2 months to a completely flat scar (1.3 mm thickness) was
      documented and remained stable at 50 months of follow-up. Amelanotic choroidal
      melanoma with incomplete response following conventional plaque radiotherapy can
      be treated with verteporfin PDT for consolidation.

PMID- 22589359
TI  - A spuriously 'normal' haemoglobin A1c result.
AB  - We report a case of spuriously 'normal' haemoglobin A1c (HbA1c) result due to
      misidentification of HbG Taipei as HbAo by the Variant II built-in retention time
      algorithm. The defect was circumvented effectively by the implementation of a
      chromatographic system specific internal quality control mechanism for peak
      identity verification. HbA1c and estimated average glucose results were corrected
      from 4.7% to 8.2%, and 4.9 to 10.5 mmol/L, respectively. The results were
      consistent with the patient's concurrent and previous fasting blood glucose
      concentrations and existence of diabetes mellitus dermopathy, indicating poor
      glycaemic control. A review of currently available analytical systems showed that
      other than mass spectrometry, HbA1c measurements by these systems were generally
      affected by the presence of haemoglobin variants. The same haemoglobin variant
      may affect different analytical systems differently, resulting in the deviation
      of HbA1c results from the true value to different extents. Including the
      analytical principle of HbA1c measurement in the laboratory report can avoid
      inappropriate comparison of results obtained by different analytical systems.
      Moreover, since individual haemoglobinopathy may affect the degree of glucose
      binding to haemoglobin in a different way, this uncertainty limits the general
      application of same decision cut-off of established guidelines for glycaemic
      control monitoring. Adoption of an individualized monitoring system based on the
      critical difference or reference change value of HbA1c can be considered.

PMID- 22589360
TI  - Can we interpret serum thyroglobulin results?
AB  - Thyroglobulin (Tg) is a tumour marker for differentiated thyroid cancer.
      Interpretation requires a knowledge of the current thyrotropin (TSH)
      concentration as secretion is TSH-dependent. While a raised serum Tg may be
      indicative of residual or recurrent thyroid cancer, trauma to the thyroid (e.g.
      surgical, biopsy or due to radioiodine treatment) also causes an increase. Tg may
      be measured when TSH is suppressed and also following recombinant TSH (rhTSH)
      stimulation. Interpretation of results in pregnancy and in children is discussed.
      Assay bias and interference by endogenous Tg antibodies (Abs) are the main
      confounders in the interpretation of results. Although there is an international
      standard for Tg, there are large differences in results and yet there are few
      assay-specific clinical decision limits. Patients should therefore be monitored
      with the same assay. Endogenous TgAbs may cause false-negative interference in
      immunometric assays and may cause false-positive results in radioimmunoassay.
      Although the measurement of TgAbs has been advocated for predicting interference,
      it is now clear that interference can still occur when TgAbs have not been
      detected, the effect being TgAb-assay-specific. Approaches to identifying those
      samples where there may be interference are discussed. The laboratory should have
      a protocol for the investigation of possible interferences and data on the bias
      of the Tg assay that they use. An appreciation of the clinical uses of the
      service is required as an understanding by endocrinologists, oncologists and
      endocrine surgeons of the analytical limitations of the service.

PMID- 22589361
TI  - SD-OCT in pigmented paravenous retinochoroidal atrophy.
AB  - Pigmented paravenous retinochoroidal atrophy (PPRCA) is a rare disease
      characterized by bilateral retinochoroidal atrophy and pigmentation along the
      retinal veins. The authors describe spectral-domain optical coherence tomography
      (SD-OCT) in a case of PPRCA. The right macula showed a lamellar macular hole. In
      addition, scans were taken through the affected areas along the retinal veins
      that revealed the location of the pigment and other features. These findings have
      not been reported previously.

PMID- 22589362
TI  - Physical and psychosocial factors associated with wrist or hand pain among
      Australian hospital-based nurses.
AB  - OBJECTIVE: To assess the personal, physical and psychosocial factors associated
      with wrist or hand pain in Australian hospital-based nurses. METHODS: Wrist or
      hand pain, associated disability and sickness absence, demographic, occupational,
      physical, psychosocial and personal factors among nurses working for three
      hospitals in Melbourne, Australia, were assessed in a cross-sectional study.
      Factors associated with wrist or hand pain in the past month were assessed using
      logistic regression. RESULTS: This analysis was based on 1111 participants. The
      prevalence of wrist or hand pain in the past month was 15.3%. Repeated movements
      of the wrist or finger >4 h (OR 2.63, 95% CI 1.80 to 3.84), high job strain
      (1.54, 1.04 to 2.28), job insecurity (1.55, 1.04 to 2.28), somatisation tendency
      (2.73, 1.75 to 4.26), pain catastrophising (1.56, 1.03 to 2.37), better mental
      (0.97, 0.95 to 0.99) and physical (0.96, 0.94-0.98) health and well-being were
      associated with wrist or hand pain in the past month, after adjusting for
      possible confounding factors. When all significant factors were examined in the
      same model, repeated movements of the wrist or finger >4 h (2.50, 1.71 to 3.67),
      somatisation (2.61, 1.65 to 4.13) and better physical health and well-being
      (0.96, 0.94 to 0.99) remained independently associated with wrist or hand pain in
      the past month. CONCLUSIONS: This study highlights that wrist or hand pain is
      prevalent in hospital nurses. Workplace physical factors and personal factors
      were associated with wrist or hand pain. Further longitudinal investigation is
      needed to examine the predictive nature of these factors.

PMID- 22589363
TI  - The impact of immersion protection requirements on hair dryer electrocutions in
      the USA.
AB  - OBJECTIVE: To evaluate the effectiveness of the immersion protection requirements
      of a voluntary safety standard for portable handheld hair dryers in preventing
      electrocution deaths in the USA. METHODS: The present work was an interrupted
      time series study design. Data on annual hair dryer-related electrocution deaths
      resulting from water contact were developed for the 1980-2007 study period. A
      multivariate Poisson regression model for rate data was used to evaluate the
      impact of the immersion protection requirements during the post-intervention
      period. The analysis controlled for the estimated number of hair dryers in use
      and the estimated number of US homes equipped with ground fault circuit
      interrupters, safety devices that would address hair dryer electrocutions even in
      the absence of the immersion protection requirements of the voluntary standard.
      The implementation of the 1987 and 1991 immersion protection requirements of the
      voluntary standard for portable handheld hair dryers was the intervention
      studied. The main outcome measure was the estimated reduction in the hair dryer
      electrocution rate associated with the immersion protection requirements of the
      voluntary standard. RESULTS: After controlling for covariates, the immersion
      protection requirements were estimated to reduce the rate of hair dryer immersion
      electrocution deaths by 96.6% (95% CI, 90.8% to 98.8%). This suggests the
      prevention of about 280 immersion electrocution deaths involving hair dryers
      during the post-intervention period (1987-2007). CONCLUSIONS: The immersion
      protection requirements of the voluntary safety standard for hair dryers have
      been highly effective in reducing hair dryer electrocutions.

PMID- 22589364
TI  - Estimating glomerular filtration rate using the chronic kidney disease
      epidemiology collaboration creatinine equation: better risk predictions.

PMID- 22589365
TI  - Fine-tuning a heart-brain connection: anxiety in atrial fibrillation.

PMID- 22589366
TI  - Targeting the beta-adrenergic receptor system through G-protein-coupled receptor
      kinase 2: a new paradigm for therapy and prognostic evaluation in heart failure:
      from bench to bedside.

PMID- 22589367
TI  - Apical pseudoaneurysm following continuous flow left ventricular assist device
      placement.

PMID- 22589368
TI  - Improvement in myocardial delayed enhancement after autologous stem cell
      transplant in a patient with light chain amyloidosis.

PMID- 22589370
TI  - At risk for schizophrenic or affective psychoses? A meta-analysis of DSM/ICD
      diagnostic outcomes in individuals at high clinical risk.
AB  - BACKGROUND: The clinical high-risk state for psychosis (HRP) is associated with
      an enhanced probability of developing a psychotic episode over a relatively short
      period of time. However, the extent to which different diagnostic types of
      illness develop remains unclear. METHODS: A systematic review was performed to
      identify studies of HRP participants reporting International Classfication of
      Diseases/Diagnostic and Statistical Manual of Mental Disorders diagnostic
      outcomes at follow-up. Demographic, clinical, and methodological variables were
      extracted from each publication or obtained directly from its authors. A meta
      analysis was performed of transition to schizophrenic (SP) or affective psychoses
      (AP) and to specific diagnostic categories. Statistical heterogeneity and small
      study bias were assessed, and meta-regressions were performed. RESULTS: Twenty
      three studies were retrieved, including a total of 2182 HRP participants, 560
      (26%) of them developed a frank psychotic disorder over the follow-up time (mean
      = 2.35 y). Among HRP participants who developed psychosis, 73% were diagnosed
      with SP and only 11% with AP (Risk Ratio, RR = 5.43, 95% CI from 3.35 to 8.83).
      The specific transition risk to ICD/DSM schizophrenia was of 15.7% (over 2.35y).
      Heterogeneity was statistically significant and moderate in magnitude. Use of
      basic symptoms criteria in the baseline clinical assessment was associated with a
      further increase in the proportion progressing to SP vs AP (RR = 17.1). There was
      no evidence of publication bias and the sensitivity analysis confirmed robustness
      of the above results. CONCLUSIONS: The HRP state is heterogeneous in term of
      longitudinal diagnoses; however, the current HRP diagnostic criteria appear
      strongly biased toward an identification of early phases of SP rather than AP.

PMID- 22589371
TI  - Skin ceramide alterations in first-episode schizophrenia indicate abnormal
      sphingolipid metabolism.
AB  - There is considerable evidence for specific pathology of lipid metabolism in
      schizophrenia, affecting polyunsaturated fatty acids and in particular
      sphingolipids. These deficits are assumed to interfere with neuronal membrane
      functioning and the development and maintenance of myelin sheaths. Recent studies
      suggest that some of these lipid pathologies might also be detected in peripheral
      skin tests. In this study, we examined different skin lipids and their relation
      to schizophrenia. We assessed epidermal lipid profiles in 22 first-episode
      antipsychotic-naive schizophrenia patients and 22 healthy controls matched for
      age and gender using a hexan/ethanol extraction technique and combined high
      performance thin-layer chromatography/gas-chromatography. We found highly
      significant increase of ceramide AH and NH/AS classes in patients and decrease of
      EOS and NP ceramide classes. This is the first demonstration of specific
      peripheral sphingolipid alterations in schizophrenia. The results support recent
      models of systemic lipid pathology and in particular of specific sphingolipids,
      which are crucial in neuronal membrane integrity. Given recent findings showing
      amelioration of psychopathology using fatty acid supplementation, our findings
      also bear relevance for sphingolipids as potential biomarkers of the disease.

PMID- 22589373
TI  - Lung ultrasound for the screening of interstitial lung disease in very early
      systemic sclerosis.
AB  - BACKGROUND: A high percentage of patients with systemic sclerosis (SSc) develop
      interstitial lung disease (ILD) during the course of the disease. Promising data
      have recently shown that lung ultrasound (LUS) is able to detect ILD by the
      evaluation of B-lines (previously called ultrasound lung comets), the sonographic
      marker of pulmonary interstitial syndrome. OBJECTIVE: To evaluate whether LUS is
      reliable in the screening of ILD in patients with SSc. METHODS: Fifty-eight
      consecutive patients with SSc (54 women, mean age 51+/-14 years) who underwent a
      high resolution CT (HRCT) scan of the chest were also evaluated by LUS for
      detection of B-lines. Of these, 32 patients (29 women, mean age 51+/-15 years)
      fulfilled the criteria for a diagnosis of very early SSc. RESULTS: At HRCT, ILD
      was detected in 88% of the SSc population and in 41% of the very early SSc
      population. A significant difference in the number of B-lines was found in
      patients with and without ILD on HRCT (57+/-53 vs 9+/-9; p<0.0001), with a
      concordance rate of 83%. All discordant cases were false positive at LUS,
      providing a sensitivity and negative predictive value of 100% in both SSc and
      very early SSc. CONCLUSIONS: ILD may be detected in patients with very early SSc.
      The presence of B-lines at LUS examination correlates with ILD at HRCT. LUS is
      very sensitive for detecting ILD even in patients with a diagnosis of very early
      SSc. The use of LUS as a screening tool for ILD may be feasible to guide further
      investigation with HRCT.

PMID- 22589372
TI  - Enhanced angiogenic and cardiomyocyte differentiation capacity of epigenetically
      reprogrammed mouse and human endothelial progenitor cells augments their efficacy
      for ischemic myocardial repair.
AB  - RATIONALE: Although bone marrow endothelial progenitor cell (EPC)-based therapies
      improve the symptoms in patients with ischemic heart disease, their limited
      plasticity and decreased function in patients with existing heart disease limit
      the full benefit of EPC therapy for cardiac regenerative medicine. OBJECTIVE: We
      hypothesized that reprogramming mouse or human EPCs, or both, using small
      molecules targeting key epigenetic repressive marks would lead to a global
      increase in active gene transcription, induce their cardiomyogenic potential, and
      enhance their inherent angiogenic potential. METHOD AND RESULTS: Mouse Lin
      Sca1(+)CD31(+) EPCs and human CD34(+) cells were treated with inhibitors of DNA
      methyltransferases (5-Azacytidine), histone deacetylases (valproic acid), and G9a
      histone dimethyltransferase. A 48-hour treatment led to global increase in active
      transcriptome, including the reactivation of pluripotency-associated and
      cardiomyocyte-specific mRNA expression, whereas endothelial cell-specific genes
      were significantly upregulated. When cultured under appropriate differentiation
      conditions, reprogrammed EPCs showed efficient differentiation into
      cardiomyocytes. Treatment with epigenetic-modifying agents show marked increase
      in histone acetylation on cardiomyocyte and pluripotent cell-specific gene
      promoters. Intramyocardial transplantation of reprogrammed mouse and human EPCs
      in an acute myocardial infarction mouse model showed significant improvement in
      ventricular functions, which was histologically supported by their de novo
      cardiomyocyte differentiation and increased capillary density and reduced
      fibrosis. Importantly, cell transplantation was safe and did not form teratomas.
      CONCLUSIONS: Taken together, our results suggest that epigenetically reprogrammed
      EPCs display a safe, more plastic phenotype and improve postinfarct cardiac
      repair by both neocardiomyogenesis and neovascularization.

PMID- 22589374
TI  - European registry of babies born to mothers with antiphospholipid syndrome.
AB  - OBJECTIVES: This study aimed to describe the long-term outcome and immunological
      status of children born to mothers with antiphospholipid syndrome, to determine
      the factors responsible for childhood abnormalities, and to correlate the child's
      immunological profile with their mothers. METHODS: A prospective follow-up of a
      European multicentre cohort was conducted. The follow-up consisted of clinical
      examination, growth data, neurodevelopmental milestones and antiphospholipid
      antibodies (APL) screening. Children were examined at 3, 9, 24 months and 5
      years. RESULTS: 134 children were analysed (female sex in 65 cases, birth weight
      3000+/-500 g, height 48+/-3 cm). Sixteen per cent had a preterm birth (<37 weeks;
      n=22), and 14% weighted less than 2500 g at birth (n=19). Neonatal complications
      were noted in 18 cases (13%), with five infections (4%). During the 5-year follow
      up, no thrombosis or systemic lupus erythematosus (SLE) was noted. Four children
      displayed behavioural abnormalities, which consisted of autism, hyperactive
      behaviour, feeding disorder with language delay and axial hypotony with
      psychomotor delay. At birth lupus anticoagulant was present in four (4%),
      anticardiolipin antibodies (ACL) IgG in 18 (16%), anti-beta(2) glycoprotein-I
      (anti-beta2GPI) IgG/M in 16 (15%) and three (3%), respectively. ACL IgG and anti
      beta2GPI disappeared at 6 months in nine (17%) and nine (18%), whereas APL
      persisted in 10% of children. ACL and anti-beta2GPI IgG were correlated with the
      same mother's antibodies before 6 months of age (p<0.05). CONCLUSION: Despite the
      presence of APL in children, thrombosis or SLE were not observed. The presence of
      neurodevelopmental abnormalities seems to be more important in these children,
      and could justify long-term follow-up.

PMID- 22589375
TI  - Immunogenicity and safety of a quadrivalent human papillomavirus vaccine in
      patients with systemic lupus erythematosus: a case-control study.
AB  - OBJECTIVES: To evaluate the immunogenicity and safety of GARDASIL, a quadrivalent
      human papillomavirus (HPV) vaccine, in patients with systemic lupus erythematosus
      (SLE). METHODS: Women with SLE aged 18-35 years who had stable disease were
      recruited to receive GARDASIL vaccination and an equal number of age-matched
      healthy women were also vaccinated. Seroconversion rates of antibodies to HPV
      serotypes 6, 11, 16 and 18 at months 7 and 12 and adverse events (AEs) were
      compared between patients and controls. The rate of disease flares in SLE
      participants was compared with matched SLE controls. RESULTS: 50 patients with
      SLE and 50 healthy controls were studied. The mean age and disease duration of
      the patients was 25.8+/-3.9 years and 6.6+/-4.5 years, respectively. At month 12
      the seroconversion rates of anti-HPV serotypes 6, 11, 16 and 18 in patients and
      controls were 82%, 89%, 95%, 76% and 98%, 98%, 98%, 80%, respectively. In
      patients with SLE there were no significant changes in the titres of anti-dsDNA,
      complements, anti-C1q and SLE Disease Activity Index scores from baseline to
      months 2, 7 and 12. There was one mild/moderate SLE flare at months 0-2, two
      mild/moderate flares at months 3-6 and six mild/moderate and two severe flares at
      months 7-12. Disease flares in patients with SLE occurred at a similar frequency
      to that of 50 matched SLE controls (0.22/patient/year vs 0.20/patient/year,
      p=0.81). Injection site reaction was the commonest AE (5%), and the incidence of
      AEs was comparable between patients with SLE and controls. CONCLUSIONS: The
      quadrivalent HPV vaccine is well tolerated and reasonably effective in patients
      with stable SLE and does not induce an increase in lupus activity or flares.

PMID- 22589376
TI  - Chemokine receptor CCR1 antagonist CCX354-C treatment for rheumatoid arthritis:
      CARAT-2, a randomised, placebo controlled clinical trial.
AB  - OBJECTIVES: CCX354-C is a specific, orally administered antagonist of the C-C
      chemokine receptor 1, which regulates migration of monocytes and macrophages to
      synovial tissue. This clinical trial evaluated the safety and efficacy of CCX354
      C in patients with rheumatoid arthritis (RA). METHODS: CARAT-2 is a 12-week
      double-blind, randomised, placebo controlled trial in 160 patients with RA, with
      68 tender joint count and 66 swollen joint count >=8 and C-reactive protein (CRP)
      >5 mg/l, despite being on methotrexate for at least 16 weeks. Subjects received
      placebo, CCX354-C 100 mg twice daily, or 200 mg once daily for 12 weeks.
      Endpoints included safety (primary) and RA disease activity assessments based on
      American College of Rheumatology (ACR) response, and changes in 28-joint disease
      activity score-CRP, individual ACR components, as well as soluble bone turnover
      markers. RESULTS: CCX354-C was generally well tolerated by study subjects. The
      ACR20 response at week 12 was 39% in the placebo group, 43% in the 100 mg twice
      daily group (difference and 95% CI compared with placebo, 4.5 (-14.1 to 23.1);
      p=0.62) and 52% in the 200 mg once daily group (13.0 (-5.8 to 31.8); p=0.17) in
      the intention-to-treat population, and 30% in the placebo group, 44% in the 100
      mg twice daily group (14.4 (-5.9 to 34.8); p=0.17), and 56% in the 200 mg once
      daily group (25.8 (5.3 to 46.4); p=0.01) in the prespecified population of
      patients satisfying CRP and joint count eligibility criteria at the screening and
      day 1 (predose) visits. CONCLUSIONS: CCX354-C exhibited a good safety and
      tolerability profile and evidence of clinical activity in RA.

PMID- 22589377
TI  - HDL protein composition alters from proatherogenic into less atherogenic and
      proinflammatory in rheumatoid arthritis patients responding to rituximab.
AB  - OBJECTIVE: An atherogenic lipid profile is an established risk factor for
      cardiovascular (CV) diseases. Interestingly, high inflammatory states as present
      in rheumatoid arthritis (RA) are associated with unfavourable lipid profile. Data
      about effects of novel immunomodulating agents as rituximab (RTX) on lipid
      profile are limited. Therefore, changes in lipids in RTX treated RA patients were
      evaluated. METHODS: In 49 consecutive RTX treated RA patients, serum and EDTA
      plasma samples were collected at baseline, 1, 3 and 6 months. In these samples,
      lipid and levels were assessed to determine changes in time. Surface-enhanced
      laser desorption/ionisation time-of-flight (SELDI-TOF) MS analysis was performed
      in six good and six non-responding RA patients to study functional high density
      lipoprotein (HDL) protein composition changes in time. RESULTS: In the total
      group (n=49), the atherogenic index decreased from 4.3 to 3.9 (~9%) after 6
      months. Testing for effect modification revealed a difference in the effect on
      lipid levels between responders and non-responders upon RTX (p<0.001). ApoB to
      ApoA-I ratios decreased significantly (~9%) in good responding (n=32) patients.
      SELDI-TOF MS analysis revealed a significant decrease in density of mass charge
      (m/z) marker 11743, representing a decrease in serum amyloid A, in good
      responding patients. CONCLUSION: This study indicates beneficial effects on
      cholesterol profile upon RTX treatment along with improvement of disease
      activity. Proteomic analysis of the HDL particle reveals composition changes from
      proatherogenic to a less proatherogenic composition during 6 months RTX
      treatment. Whether these HDL particle alterations during immunotherapies result
      in a lower CV event rate remains to be established.

PMID- 22589378
TI  - Relapse patterns in IgG4-related disease.

PMID- 22589379
TI  - Gender difference in disease expression, radiographic damage and disability among
      patients with psoriatic arthritis.
AB  - OBJECTIVE: The authors aimed to assess gender-related differences in severity of
      psoriatic arthritis (PsA) as reflected by measures of disease activity, joint
      damage, quality of life and disability. METHODS: A cross-sectional analysis was
      performed among patients who have been followed in a large PsA clinic.
      Demographic, clinical and radiographic data as well as information about quality
      of life and function were retrieved from the clinic database. Radiographic damage
      was assessed according to modified Steinbrocker score (mSS). The association
      between gender and the following outcome variables, radiographic joint damage,
      axial involvement and measures of quality of life and function, was assessed by
      multivariate regression analysis after adjustment for potential confounders.
      RESULTS: Three hundred and forty-five men and 245 women were included in the
      study. Axial involvement was more frequent in men (42.9% vs 31%, p=0.003). In
      multivariate analysis, adjusting for potential confounders, men were more likely
      to develop axial involvement (OR 1.8, p=0.003). Men were also more likely to
      develop more severe radiographic damage in the peripheral joints as evident by
      mSS. Men were more likely to be in a higher mSS damage category compared with
      women after adjusting for potential confounders in multivariate analysis (OR 1.6,
      p=0.007). Women suffered from more severe limitations in function and worse
      quality of life compared with men based on several patients' reported outcomes.
      CONCLUSIONS: Men with PsA are more likely to develop axial involvement and
      radiographic joint damage, while women are more likely to report about limitation
      in function and impaired quality of life.

PMID- 22589380
TI  - Detection, scoring and volume assessment of bone erosions by ultrasonography in
      rheumatoid arthritis: comparison with CT.
AB  - OBJECTIVES: To determine the accuracy of ultrasonography (US) for bone erosion
      detection in different areas of rheumatoid arthritis (RA) metacarpophalangeal
      (MCP) joints with multislice CT as the reference method. Second, to establish the
      necessary bone volume loss on CT for US to reliably detect it as an erosion, and
      finally to compare two semiquantitative US-erosion scoring methods. METHODS: The
      2nd-5th MCP joints of 49 patients with RA were examined by CT and US, and
      evaluated for the presence of bone erosion in each MCP joint quadrant. On CT,
      erosion volume was scored according to the OMERACT-RAMRIS score (bone volume loss
      in 10% increments of original bone volume). US erosions were scored 0-3 according
      to the Szkudlarek and Scoring by UltraSound Structural erosion (ScUSSe) systems,
      respectively. RESULTS: Seven hundred and eighty-four MCP joint quadrants were
      examined. Erosions were detected by CT in 259 quadrants and by US in 142
      quadrants. Sensitivity/specificity/accuracy of US was overall 44%/95%/78%
      compared with 71%/95%/90% in areas with good US accessibility (radial 2nd MCP,
      ulnar 5th MCP and all dorsal/palmar aspects). US detected 95% of erosions with
      bone volume loss >20%. In US accessible areas, 63% of erosions with 1-10% bone
      volume loss and 94% of erosions with >10% bone loss were detected. The two US
      scoring systems agreed well on large erosions, whereas the smallest erosions
      (Szkudlarek grade 1, of which 86% were confirmed by CT) were not scored by
      ScUSSe. CONCLUSION: In accessible areas, US was highly accurate for detection and
      semiquantitative assessment of RA bone erosion. Even the smallest erosions, only
      detected in one plane, were generally confirmed by CT.

PMID- 22589381
TI  - Lack of microsomal prostaglandin E(2) synthase-1 in bone marrow-derived myeloid
      cells impairs left ventricular function and increases mortality after acute
      myocardial infarction.
AB  - BACKGROUND: Microsomal prostaglandin E(2) synthase-1 (mPGES-1), encoded by the
      Ptges gene, catalyzes prostaglandin E(2) biosynthesis and is expressed by
      leukocytes, cardiac myocytes, and cardiac fibroblasts. Ptges(-/-) mice develop
      more left ventricle (LV) dilation, worse LV contractile function, and higher LV
      end-diastolic pressure than Ptges(+/+) mice after myocardial infarction. In this
      study, we define the role of mPGES-1 in bone marrow-derived leukocytes in the
      recovery of LV function after coronary ligation. METHODS AND RESULTS: Cardiac
      structure and function in Ptges(+/+) mice with Ptges(+/+) bone marrow (BM(+/+))
      and Ptges(+/+) mice with Ptges(-/-) BM (BM(-/-)) were assessed by morphometric
      analysis, echocardiography, and invasive hemodynamics before and 7 and 28 days
      after myocardial infarction. Prostaglandin levels and prostaglandin biosynthetic
      enzyme gene expression were measured by liquid chromatography-tandem mass
      spectrometry and real-time polymerase chain reaction, immunoblotting,
      immunohistochemistry, and immunofluorescence microscopy, respectively. After
      myocardial infarction, BM(-/-) mice had more LV dilation, worse LV systolic and
      diastolic function, higher LV end-diastolic pressure, more cardiomyocyte
      hypertrophy, and higher mortality but similar infarct size and pulmonary edema
      compared with BM(+/+) mice. BM(-/-) mice also had higher levels of COX-1 protein
      and more leukocytes in the infarct, but not the viable LV, than BM(+/+) mice.
      Levels of prostaglandin E(2) were higher in the infarct and viable myocardium of
      BM(-/-) mice than in BM(+/+) mice. CONCLUSIONS: Lack of mPGES-1 in bone marrow
      derived leukocytes negatively regulates COX-1 expression, prostaglandin E(2)
      biosynthesis, and inflammation in the infarct and leads to impaired LV function,
      adverse LV remodeling, and decreased survival after acute myocardial infarction.

PMID- 22589382
TI  - Prostaglandin E2 in remote control of myocardial remodeling.

PMID- 22589383
TI  - Racial and ethnic differences in wait-list outcomes in patients listed for heart
      transplantation in the United States.
AB  - BACKGROUND: Racial differences in long-term survival after heart transplant (HT)
      are well known. We sought to assess racial/ethnic differences in wait-list
      outcomes among patients listed for HT in the United States in the current era.
      METHODS AND RESULTS: We compared wait-list and posttransplant in-hospital
      mortality among white, black, and Hispanic patients >= 18 years of age listed for
      their primary HT in the United States between July 2006 and September 2010. Of 10
      377 patients analyzed, 71% were white, 21% were black, and 8% were Hispanic.
      Black and Hispanic patients were more likely to be listed with higher urgency
      (listing status 1A/1B) in comparison with white patients (P<0.001). Overall,
      10.5% of white, 11.6% of black, and 13.4% of Hispanic candidates died on the wait
      list or became too sick for a transplant within 1 year of listing. After
      adjusting for baseline risk factors, Hispanic patients were at higher risk of
      wait-list mortality (hazard ratio 1.51, 95% CI 1.23, 1.85) in comparison with
      white patients, but not black patients (hazard ratio 1.13, 95% CI 0.97, 1.31). In
      comparison with white HT recipients, posttransplant in-hospital mortality was
      higher in black recipients (odds ratio 1.53, 95% CI 1.15, 2.03) but was not
      different in Hispanic recipients (odds ratio 0.78, 95% CI 0.48, 1.29).
      CONCLUSIONS: Hispanic patients listed for HT in the United States appear to be at
      higher risk of dying on the wait-list or becoming too sick for a transplant in
      comparison with white patients. Black patients are not at higher risk of wait
      list mortality, but they have higher early posttransplant mortality.

PMID- 22589385
TI  - Computational systems biology and in silico modeling of the human microbiome.
AB  - The human microbiome is a complex biological system with numerous interacting
      components across multiple organizational levels. The assembly, ecology and
      dynamics of the microbiome and its contribution to the development, physiology
      and nutrition of the host are clearly affected not only by the set of genes or
      species in the microbiome but also by the way these genes are linked across
      numerous pathways and by the interactions between the various species. To date,
      however, most studies of the human microbiome have focused on characterizing the
      composition of the microbiome and on comparative analyses, whereas significantly
      less effort has been directed at elucidating, characterizing and modeling these
      interactions and on studying the microbiome as a complex, interconnected and
      cohesive system. Here, specifically, I highlight the pressing need for the
      development of predictive system-level models and for a system-level
      understanding of the microbiome, and discuss potential computational frameworks
      for metagenomic-based modeling of the microbiome at the cellular, ecological and
      supra-organismal level. I review some preliminary attempts at constructing such
      models and examine the challenges and hurdles that such modeling efforts face. I
      also discuss possible future applications and research avenues that such
      metagenomic systems biology and predictive system-level models may facilitate.

PMID- 22589386
TI  - The structure of the full-length tetrameric PKA regulatory RIIbeta complex
      reveals the mechanism of allosteric PKA activation.
AB  - The catalytic activity of protein kinases is usually tightly controlled by
      posttranslational modifications and diverse sets of regulatory proteins. Protein
      kinases are highly dynamic enzymes, and structures of kinases in various
      activation states and costructures with regulatory proteins have provided
      critical insights into the complex regulatory mechanisms of this large and
      diverse protein family. The crystal structure of protein kinase A (PKA) provided
      a reference model for our understanding of kinase catalytic function. Now, more
      than two decades later, the high-resolution model of a full-length tetrameric PKA
      holoenzyme has been published, revealing the structural mechanisms underlying
      allosteric PKA activation.

PMID- 22589384
TI  - Bioinformatics opportunities for identification and study of medicinal plants.
AB  - Plants have been used as a source of medicine since historic times and several
      commercially important drugs are of plant-based origin. The traditional approach
      towards discovery of plant-based drugs often times involves significant amount of
      time and expenditure. These labor-intensive approaches have struggled to keep
      pace with the rapid development of high-throughput technologies. In the era of
      high volume, high-throughput data generation across the biosciences,
      bioinformatics plays a crucial role. This has generally been the case in the
      context of drug designing and discovery. However, there has been limited
      attention to date to the potential application of bioinformatics approaches that
      can leverage plant-based knowledge. Here, we review bioinformatics studies that
      have contributed to medicinal plants research. In particular, we highlight areas
      in medicinal plant research where the application of bioinformatics methodologies
      may result in quicker and potentially cost-effective leads toward finding plant
      based remedies.

PMID- 22589387
TI  - The structural basis of DKK-mediated inhibition of Wnt/LRP signaling.
AB  - Low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) mediate
      canonical Wnt-beta-catenin signaling by forming a complex with the co-receptor
      Frizzled, which binds to Wnt proteins. Dickkopf (DKK)-related proteins inhibit
      the Wnt signaling pathway by directly binding to the ectodomains of LRP5/6.
      However, the mechanism for DKK-mediated antagonism has not been fully understood
      as of yet. Crystal structures of the LRP6 ectodomain in complex with DKK1, along
      with mutagenesis studies, provide considerable insights into the molecular basis
      for DKK-mediated inhibition and Wnt signaling through LRP5/6.

PMID- 22589388
TI  - Roles of GRK2 in cell signaling beyond GPCR desensitization: GRK2-HDAC6
      interaction modulates cell spreading and motility.
AB  - G protein-coupled receptor kinase 2 (GRK2) is a ubiquitous, essential protein
      kinase that is emerging as an integrative node in many signaling networks.
      Moreover, changes in GRK2 abundance and activity have been identified in several
      inflammatory, cardiovascular disease, and tumor contexts, suggesting that those
      alterations may contribute to the initiation or development of pathologies. GRKs
      were initially identified as key players in the desensitization and
      internalization of multiple G protein-coupled receptors (GPCRs), but GRK2 also
      phosphorylates several non-GPCR substrates and dynamically associates with a
      variety of proteins related to signal transduction. Ongoing research in our
      laboratory is aimed at understanding how specific GRK2 interactomes are
      orchestrated in a stimulus-, context-, or cell type-specific manner. We have
      recently identified an interaction between GRK2 and histone deacetylase 6 (HDAC6)
      that modulates cell spreading and motility. HDAC6 is a major cytoplasmic a
      tubulin deacetylase that is involved in cell motility and adhesion. GRK2
      dynamically and directly associates with and phosphorylates HDAC6 to stimulate
      its a-tubulin deacetylase activity at specific cellular localizations, such as
      the leading edge of migrating cells, thus promoting local tubulin deacetylation
      and enhanced motility. GRK2-HDAC6-mediated regulation of tubulin acetylation also
      modulates cellular spreading. This GRK2-HDAC6 functional interaction may have
      important implications in pathological contexts related to epithelial cell
      migration.

PMID- 22589390
TI  - IGF-IR signaling attenuates the age-related decline of diastolic cardiac
      function.
AB  - Insulin-like growth factor (IGF-I) signaling has been implicated to play an
      important role in regulation of cardiac growth, hypertrophy, and contractile
      function and has been linked to the development of age-related congestive heart
      failure. Here, we address the question to what extent cardiomyocyte-specific IGF
      I signaling is essential for maintenance of the structural and functional
      integrity of the adult murine heart. To investigate the effects of IGF-I
      signaling in the adult heart without confounding effects due to IGF-I
      overexpression or adaptation during embryonic and early postnatal development, we
      inactivated the IGF-I receptor (IGF-IR) by a 4-hydroxytamoxifen-inducible Cre
      recombinase in adult cardiac myocytes. Efficient inactivation of the IGF-IR
      (iCMIGF-IRKO) as assessed by Western analysis and real-time PCR went along with
      reduced IGF-I-dependent Akt and GSK3beta phosphorylation. Functional analysis by
      conductance manometry and MRI revealed no functional alterations in young adult
      iCMIGF-IRKO mice (age 3 mo). However, when induced in aging mice (11 mo)
      diastolic cardiac function was depressed. To address the question whether insulin
      signaling might compensate for the defective IGF-IR signaling, we inactivated
      beta-cells by streptozotocin. However, the diabetes-associated functional
      depression was similar in control and iCMIGF-IRKO mice. Similarly, analysis of
      the cardiac gene expression profile on 44K microarrays did not reveal activation
      of overt adaptive processes. Endogenous IGF-IR signaling is required for
      conservation of cardiac function of the aging heart, but not for the integrity of
      cardiac structure and function of young hearts.

PMID- 22589389
TI  - MicroSCALE screening reveals genetic modifiers of therapeutic response in
      melanoma.
AB  - Cell microarrays are a promising tool for performing large-scale functional
      genomic screening in mammalian cells at reasonable cost, but owing to technical
      limitations they have been restricted for use with a narrow range of cell lines
      and short-term assays. Here, we describe MicroSCALE (Microarrays of Spatially
      Confined Adhesive Lentiviral Features), a cell microarray-based platform that
      enables application of this technology to a wide range of cell types and longer
      term assays. We used MicroSCALE to uncover kinases that when overexpressed
      partially desensitized B-RAFV600E-mutant melanoma cells to inhibitors of the
      mitogen-activated protein kinase kinase kinase (MAPKKK) RAF, the MAPKKs MEK1 and
      2 (MEK1/2, mitogen-activated protein kinase kinase 1 and 2), mTOR (mammalian
      target of rapamycin), or PI3K (phosphatidylinositol 3-kinase). These screens
      indicated that cells treated with inhibitors acting through common mechanisms
      were affected by a similar profile of overexpressed proteins. In contrast,
      screens involving inhibitors acting through distinct mechanisms yielded unique
      profiles, a finding that has potential relevance for small-molecule target
      identification and combination drugging studies. Further, by integrating large
      scale functional screening results with cancer cell line gene expression and
      pharmacological sensitivity data, we validated the nuclear factor kappaB pathway
      as a potential mediator of resistance to MAPK pathway inhibitors. The MicroSCALE
      platform described here may enable new classes of large-scale, resource-efficient
      screens that were not previously feasible, including those involving combinations
      of cell lines, perturbations, and assay outputs or those involving limited
      numbers of cells and limited or expensive reagents.

PMID- 22589391
TI  - The effects of 13 wk of liraglutide treatment on endocrine and exocrine pancreas
      in male and female ZDF rats: a quantitative and qualitative analysis revealing no
      evidence of drug-induced pancreatitis.
AB  - A possible association between glucagon-like peptide-1 (GLP-1) analogs and
      incidences of pancreatitis has been suggested based on clinical studies. In male
      and female diabetic Zucker diabetic fatty (ZDF) rats, we investigated the effects
      of continuous administration of liraglutide and exenatide on biochemical [lipase,
      pancreatic amylase (P-amylase)] and histopathological markers of pancreatitis.
      Male and female ZDF rats were dosed for 13 wk with liraglutide (0.4 or 1.0 mg.kg(
      1).day(-1) sc once daily) or exenatide (0.25 mg.kg(-1).day(-1) sc, Alzet osmotic
      minipumps). P-amylase and lipase plasma activity were measured, and an extended
      histopathological and stereological (specific cell mass and proliferation rate)
      evaluation of the exocrine and the endocrine pancreas was performed. Expectedly,
      liraglutide and exenatide lowered blood glucose and Hb A(1c) in male and female
      ZDF rats, whereas beta-cell mass and proliferation rate were increased with
      greatly improved blood glucose control. Whereas neither analog affected lipase
      activity, small increases in P-amylase activity were observed in animals treated
      with liraglutide and exenatide. However, concurrent or permanent increases in
      lipase and P-amylase activity were never observed. Triglycerides were lowered by
      both GLP-1 analogs. The qualitative histopathological findings did not reveal
      adverse effects of liraglutide. The findings were mainly minimal in severity and
      focal in distribution. Similarly, the quantitative stereological analyses
      revealed no effects of liraglutide or exenatide on overall pancreas weight or
      exocrine and duct cell mass or proliferation. The present study demonstrates
      that, in overtly diabetic male and female ZDF rats, prolonged exposure to GLP-1
      receptor agonists does not affect biochemical or histopathological markers of
      pancreatitis, and whereas both exenatide and liraglutide increase beta-cell mass,
      they have no effect on the exocrine pancreas. However, clinical outcome studies
      and studies using primate tissues and/or studies in nonhuman primates are needed
      to further assess human risk.

PMID- 22589392
TI  - Development and characterization of a novel CD19CherryLuciferase (CD19CL)
      transgenic mouse for the preclinical study of B-cell lymphomas.
AB  - PURPOSE: To generate a transgenic mouse that when crossed with spontaneous mouse
      models of lymphoma will allow for quantitative in vivo measurement of tumor
      burden over the entire spectrum of the disease and or response to therapy in a
      "disease" or lymphoma subtype-specific manner. EXPERIMENTAL DESIGN: We developed
      a novel genetically engineered transgenic mouse using a CherryLuciferase fusion
      gene targeted to the CD19 locus to achieve B-cell-restricted fluorescent
      bioluminescent emission in transgenic mouse models of living mice. The use of a
      dual function protein enables one to link the in vivo analysis via
      bioluminescence imaging to cell discriminating ex vivo analyses via fluorescence
      emission. RESULTS: The spatiotemporal tracking of B-cell lymphoma growth and the
      response of an established B-cell lymphoma to a drug known to induce remission
      was evaluated in a double transgenic animal obtained by crossing the
      CD19CherryLuciferase transgenic mouse to a mouse model of an aggressive B-cell
      lymphoma. The observations validated the use of the CD19CherryLuciferase
      transgenic mouse in the assessment of an active drug routinely used in the
      treatment of lymphoproliferative malignancies. CONCLUSIONS: The transgenic mouse
      described here is the first of its kind, intended to be used to hasten
      translational studies of novel agents in lymphoma, with the intent that
      understanding the relevant pharmacology before clinical study will accelerate
      successful development in clinical studies.

PMID- 22589393
TI  - Serum sex steroids depict a nonlinear u-shaped association with high-risk
      prostate cancer at radical prostatectomy.
AB  - PURPOSE: To assess the association between preoperative serum total testosterone
      (tT), 17beta-estradiol (E(2)), sex hormone-binding globulin (SHBG), and tT-E(2)
      ratio values with high-risk prostate cancer (as defined by the National
      Comprehensive Cancer Network practice guidelines) at radical prostatectomy.
      EXPERIMENTAL DESIGN: Serum E(2), tT, and SHBG were dosed the day before surgery
      (7:00-11:00 am) in a cohort of 724 candidates to radical prostatectomy.
      Restricted cubic spline functions tested the association between predictors
      (i.e., model 1: age, body mass index, and serum tT, E(2), and SHBG levels; model
      2: tT-E(2) values instead of tT and E(2) levels) and high-risk prostate cancer.
      RESULTS: Low-, intermediate-, or high-risk prostate cancer was found in 251
      (34.7%), 318 (43.9%), and 155 (21.4%) patients, respectively. Patients in the
      high-risk class showed the lowest tT, E(2), and tT-E(2) ratio values (all P <=
      0.02). At univariate analysis, only age, tT, E(2), and tT-E(2) ratio values were
      significantly associated with high-risk prostate cancer (all P <= 0.006). At
      multivariate analyses considering model 1 variables, age (P = 0.03), serum tT
      (all P < 0.001), and E(2) (all P <= 0.01) were associated with high-risk prostate
      cancer; only tT-E(2) ratios achieved independent predictor status for high-risk
      prostate cancer (all P < 0.001) when considering model 2. Both the lowest and the
      highest tT, E(2), and tT-E(2) values depicted a nonlinear U-shaped significant
      association with high-risk prostate cancer. CONCLUSIONS: These data showed that
      preoperative serum sex steroids are independent predictors of high-risk prostate
      cancer, depicting a nonlinear U-shaped association.

PMID- 22589394
TI  - Resistance to TRAIL is mediated by DARPP-32 in gastric cancer.
AB  - PURPOSE: Dopamine and cAMP-regulated phosphoprotein, Mr 32,000 (DARPP-32), is
      overexpressed during the gastric carcinogenesis cascade. Here, we investigated
      the role of DARPP-32 in promoting resistance to treatment with TRAIL.
      EXPERIMENTAL DESIGN: In vitro cell models including stable expression and
      knockdown of DARPP-32 were used. The role of DARPP-32 in regulating TRAIL
      dependent apoptosis was evaluated by clonogenic survival assay, Annexin V
      staining, immunofluorescence, quantitative reverse transcriptase PCR, Western
      blot, and luciferase reporter assays. RESULTS: Stable expression of DARPP-32 in
      MKN-28 cells enhanced cell survival and suppressed TRAIL-induced cytochrome c
      release and activation of caspase-8, -9, and -3. Conversely, short hairpin RNA
      mediated knockdown of endogenous DARPP-32 sensitized the resistant MKN-45 cells
      to TRAIL-induced apoptosis and enhanced TRAIL-mediated activation of caspase-8, 
      9, and -3. DARPP-32 induced BCL-xL expression through activation of Src/STAT3
      signaling, and treatment with the Src-specific inhibitor PP1 abrogated DARPP-32
      dependent BCL-xL upregulation and cell survival in MKN-28 cells. The TRAIL
      treatment induced caspase-dependent cleavage of NF-kappaBp65 protein; this
      cleavage was prevented by DARPP-32, thus maintaining NF-kappaB activity and the
      expression of its target, FLIP(S) protein. This suggests that upregulation of BCL
      xL could play a possible role in blocking the mitochondria intrinsic apoptosis
      pathway, whereas the DARPP-32 effect on the NF-kappaB/FLIP(S) axis could serve as
      an additional negative feedback loop that blocks TRAIL-induced activation of
      caspase-8. CONCLUSION: Our findings uncover a novel mechanism of TRAIL resistance
      mediated by DARPP-32, whereby it inhibits the intrinsic apoptosis pathway through
      upregulation of BCL-xL, and the extrinsic apoptosis pathway through the NF
      kappaB/FLIP(S) axis.

PMID- 22589395
TI  - Differential expression of 2',3'-cyclic-nucleotide 3'-phosphodiesterase and
      neural lineage markers correlate with glioblastoma xenograft infiltration and
      patient survival.
AB  - PURPOSE: Glioblastoma multiforme (GBM) is a poorly treated human brain cancer
      with few established clinically useful molecular prognostic markers. We
      characterized glioblastoma stem-like cells (GSC) according to developmental
      neural lineage markers and correlated their expression with patient survival.
      EXPERIMENTAL DESIGN: Immunoblot array of neural lineage markers classified five
      independently isolated human GSC lines into three classes exhibiting differential
      expression of oligodendrocyte progenitor cells (OPC), astrocyte progenitor cells
      (APC), and neural progenitor cells (NPC) markers. Immunodeficient mice were
      orthotopically implanted with each cell line to evaluate tumor infiltration and
      recipient survival. 2',3'-Cyclic-nucleotide 3'-phosphodiesterase (CNP) antigenic
      expression was used to evaluate a clinically annotated GBM tissue microarray with
      115 specimens. RESULTS: We report that molecular classification of patient
      derived GSCs using neural lineage markers show association with differential
      xenograft invasiveness, and also show significant correlation to survival in both
      the mouse model and human patients. Orthotopic implantation into immunodeficient
      mice showed Ki-67 proliferative index independent xenograft infiltration: class I
      GSCs (OPC and NPC positive) established focal lesions, class II GSCs (NPC
      positive) formed minimally invasive lesions, and class III GSCs (APC positive)
      established highly infiltrative lesions. The OPC marker, CNP also exhibited high
      expression in focal xenografts versus low expression in invasive xenografts.
      Differential CNP expression correlated with mouse model survival, and CNP
      immunoassay of a large GBM tissue microarray also showed significant differential
      patient survival. CONCLUSIONS: GSC classification with developmental neural
      lineage markers revealed CNP as a novel and potentially useful clinical prognosis
      marker, and suggests clinical importance for patient-specific GSC analysis.

PMID- 22589396
TI  - Prospective study of changes in the metabolomic profiles of men during their
      first three months of androgen deprivation therapy for prostate cancer.
AB  - PURPOSE: Androgen deprivation therapy (ADT) for prostate cancer causes an
      increase in fasting insulin and adverse changes in body composition and serum
      lipid profile. It is unknown what other metabolic alterations are caused by ADT.
      To better characterize the metabolic effects of ADT, we measured changes in
      plasma metabolomic profile at baseline and after the first 3 months of therapy.
      EXPERIMENTAL DESIGN: Fasting plasma samples were drawn from 36 subjects at
      baseline and after 3 months of gonadotropin releasing hormone (GnRH) agonist
      therapy. Extracted samples were split into equal parts for analysis on the gas
      chromatography-mass spectrometry and liquid chromatography/tandem mass
      spectrometry platforms. RESULTS: Of the 292 identified metabolites, 56 changed
      significantly (P < 0.05) from baseline to 3 months. Notable changes were grouped
      as follows: (i) Multiple steroids were lower at 3 months, consistent with the
      effect of therapy on gonadal androgen synthesis. (ii) Most bile acids and their
      metabolites were higher during treatment. Cholesterol levels changed very little.
      (iii) Markers of lipid beta-oxidation (acetyl-carnitines and ketone bodies) and
      omega-oxidation were lower at 3 months. (iv) Two previously identified biomarkers
      of insulin resistance (2-hydroxybutyrate and branch chain keto-acid dehydrogenase
      complex products) were stable to lower at 3 months. CONCLUSIONS: Unbiased
      metabolomic analyses revealed expected, novel, and unexpected results. Steroid
      levels fell, consistent with the effects of ADT. Most bile acids and their
      metabolites increased during ADT, a novel finding. Biomarkers of lipid metabolism
      and insulin resistance fell, unexpected given that ADT has been shown to increase
      fasting insulin.

PMID- 22589397
TI  - Development of a human monoclonal antibody for potential therapy of CD27
      expressing lymphoma and leukemia.
AB  - PURPOSE: The TNF receptor superfamily member CD27 is best known for its important
      role in T-cell immunity but is also recognized as a cell-surface marker on a
      number of B- and T-cell malignancies. In this article, we describe a novel human
      monoclonal antibody (mAb) specific for CD27 with properties that suggest a
      potential utility against malignancies that express CD27. EXPERIMENTAL DESIGN:
      The fully human mAb 1F5 was generated using human Ig transgenic mice and
      characterized by analytical and functional assays in vitro. Severe combined
      immunodeficient (SCID) mice inoculated with human CD27-expressing lymphoma cells
      were administered 1F5 to investigate direct antitumor effects. A pilot study of
      1F5 was conducted in non-human primates to assess toxicity. RESULTS: 1F5 binds
      with high affinity and specificity to human and macaque CD27 and competes with
      ligand binding. 1F5 activates T cells only in combination with T-cell receptor
      stimulation and does not induce proliferation of primary CD27-expressing tumor
      cells. 1F5 significantly enhanced the survival of SCID mice bearing Raji or Daudi
      tumors, which may be mediated through direct effector mechanisms such as antibody
      dependent cellular cytotoxicity. Importantly, administration of up to 10 mg/kg of
      1F5 to cynomolgus monkeys was well tolerated without evidence of significant
      toxicity or depletion of circulating lymphocytes. CONCLUSIONS: Collectively, the
      data suggest that the human mAb 1F5, which has recently entered clinical
      development under the name CDX-1127, may provide direct antitumor activity
      against CD27-expressing lymphoma or leukemia, independent of its potential to
      enhance immunity through its agonistic properties.

PMID- 22589398
TI  - Guest editorial. It's time to e-volve: taking responsibility for science
      communication in a digital age.

PMID- 22589399
TI  - Long-wavelength photosensitivity in coral planula larvae.
AB  - Light influences the swimming behavior and settlement of the planktonic planula
      larvae of coral, but little is known regarding the photosensory biology of coral
      at this or any life-history stage. Here we used changes in the electrical
      activity of coral planula tissue upon light flashes to investigate the
      photosensitivity of the larvae. Recordings were made from five species: two whose
      larvae are brooded and contain algal symbionts (Porites astreoides and Agaricia
      agaricites), and three whose larvae are spawned and lack algal symbionts
      (Acropora cervicornis, Acropora palmata,and Montastrea faveolata).
      Photosensitivity originated from the coral larva rather than from, or in addition
      to, its algal symbionts as species with and without symbionts displayed similar
      tissue-level electrical responses to light. All species exhibited as much (or
      more) sensitivity to red stimuli as to blue/green stimuli, which is consistent
      with a role for long-wavelength visible light in the preference for substrata
      observed during settlement and in facilitating vertical positioning of larvae in
      the water column.

PMID- 22589400
TI  - Exploration of the sea urchin coelomic fluid via combinatorial peptide ligand
      libraries.
AB  - The urchin Paracentrotus lividus has been characterized via previous capture and
      enhancement of low-abundance proteins with combinatorial peptide ligand libraries
      (CPLL, ProteoMiner). Whereas in the control only 26 unique gene products could be
      identified, 82 species could be detected after CPLL treatment. Due to the
      overwhelming presence of two major proteins-the toposome (a highly glycosylated,
      modified calcium-binding, iron-less transferrin) and the major yolk proteins,
      belonging to the class of cell adhesion proteins-which constituted about 70% of
      the proteome of this biological fluid and strongly interfered with the capture of
      the minority proteome, no additional proteins could be detected. Yet, at present,
      this constitutes the most thorough investigation of the proteome of this
      biological fluid.

PMID- 22589401
TI  - Larval development and metamorphosis of the deep-sea cidaroid urchin Cidaris
      blakei.
AB  - Cidaroids, one of the two major sister clades of sea urchins, first appeared
      during the lower Permian (ca. 270 mya) and are considered to represent the
      primitive form of all living echinoids. This study of Cidaris blakei, a deep-sea
      cidaroid urchin with planktotrophic larvae, provides a description of development
      from fertilization through early juvenile stages and is the first report of a
      deep-sea urchin reared through metamorphosis. C. blakei resembles other cidaroids
      in its lack of a cohesive hyaline layer, the absence of an amniotic invagination
      for juvenile rudiment formation, and the presence of spines with a single
      morphotype at metamorphosis. C. blakei differed from other cidaroids in the
      presence of an apical tuft, the extent of fenestration of postoral skeletal rods,
      the shape of juvenile spines, and an extended (14-day) lecithotrophic stage prior
      to development of a complete gut. The development of C. blakei, 120 days from
      fertilization to metamorphosis, was protracted relative to that of shallow-water
      cidaroids. Preliminary work on temperature tolerances suggests that C. blakei
      larvae would be unable to survive the warmer temperatures higher in the water
      column and are therefore unable to vertically migrate.

PMID- 22589402
TI  - Structure and formation of the unusual sperm of Patelloida latistrigata (Mollusca
      : Patellogastropoda): implications for fertilization biology.
AB  - The structure of the spermatozoa and spermatogenesis of the lottiid limpet
      Patelloida latistrigata is described by transmission electron microscopy.
      Although the lengths of the spermatozoa (about 60 MUm) and their head region
      (about 12 MUm) are similar to those of other patellogastropods, the structure of
      the sperm head and midpiece are very different. The head consists of an unusually
      large acrosome (about 11-MUm long) with a broad posterior invagination that
      houses the relatively small nucleus. The midpiece mitochondria, which are rather
      elongate with large folded tubular cristae, are housed in a cytoplasmic sheath
      posterior to the nucleus. The proximal centriole is unusually elongate (about 2
      MUm long). The axoneme that emerges from the distal centriole is surrounded
      anteriorly by the cytoplasmic sheath in which the cytoplasmic side of the plasma
      membrane has electron-dense material. The flagellum is enlarged at its terminal
      end. Spermatogenesis is similar to that described for other patellogastropods.
      Patelloida latistrigata, therefore, has spermatozoa that seem to meet the
      morphological criteria of ent-aquasperm, which raises the question of whether
      fertilization is truly external in this limpet. However, it is also possible that
      the modifications to the sperm are linked to unknown specializations of the egg
      or egg envelope.

PMID- 22589403
TI  - Are G-protein-coupled receptors involved in mediating larval settlement and
      metamorphosis of coral planulae?
AB  - Larvae of the scleractinian coral Pocillopora damicornis are induced to settle
      and metamorphose by the presence of marine bacterial biofilms, and the larvae of
      Montipora capitata respond to a combination of filamentous and crustose coralline
      algae. The primary goal of this study was to better understand metamorphosis of
      cnidarian larvae by determining what types of receptors and signal-transduction
      pathways are involved during stimulation of metamorphosis of P. damicornis and M.
      capitata. Evidence from studies on larvae of hydrozoans suggests that G-protein
      coupled receptors (GPCRs) are good candidates. Settlement experiments were
      conducted in which competent larvae were exposed to neuropharmacological agents
      that affect GPCRs and their associated signal-transduction pathways, AC/cAMP and
      PI/DAG/PKC. On the basis of the results of these experiments, we conclude that
      GPCRs and these pathways do not mediate settlement and metamorphosis in either
      coral species. Two compounds that had an effect on both species, forskolin and
      phorbol-12-myristate-13-acetate (TPA), may be acting on other cellular processes
      not related to GPCRs. This study strengthens our understanding of the underlying
      physiological mechanisms that regulate metamorphosis in coral larvae.

PMID- 22589404
TI  - Complete development of the northeast Pacific arminacean nudibranch Janolus
      fuscus.
AB  - Early life-history stages of the nudibranch Janolus fuscus (superfamily
      Arminoidea) were reared in the laboratory and collected from the field to
      document embryology, larval morphology, and pre-and post-metamorphic growth. This
      species produces Type B egg masses containing an average of 23,063 viable
      embryos. The spiral holoblastic cleavage pattern resembled that of other
      nudibranchs, with early cell divisions occurring roughly at 4-h intervals at 11
      13  degrees C. Embryos progress through a gastrula stage with cellular extensions
      covering the blastopore and a trochophore-like stage before hatching as veliger
      larvae after 10-18 days. Veligers ranged in size from 125-153.8 MUm at hatching,
      with size being positively correlated with the duration of encapsulated
      development. After a 36-41-day larval period, some veligers ceased growing at 266
      MUm and showed signs of approaching competence. Four larvae settled and two
      metamorphosed into 280-MUm juveniles on the bryozoan prey of the adults, Bugula
      pacifica, 46 and 54 days post-hatching. Average growth of pre-ovipositional (<19
      mm) J. fuscus was more rapid (8.79% per day) than growth of ovipositional
      individuals (3.52% per day). Growth continued to a maximum of 57 mm in the
      laboratory, with an estimated total lifespan of about 5 months. These data, which
      agree with concurrent field observations, suggest a subannual life cycle.

PMID- 22589405
TI  - Energy expenditure associated with softening and stiffening of echinoderm
      connective tissue.
AB  - Catch connective tissue of echinoderms at rest (in the standard state) either
      stiffens or softens in response to different kinds of stimulation. The energy
      consumption associated with the changes was estimated by measurement of the
      oxygen consumption rate (VO(2)) in three types of connective tissues-echinoid
      catch apparatus (CA), holothuroid body-wall dermis (HD), and asteroid body-wall
      dermis (AD). Mechanical stimulation by repetitive compression (10%-15% strain),
      which increased viscosity measured by creep tests, was employed for inducing the
      stiff state. Noradrenaline (10(-3) mol l(-1)), which decreased viscosity of CA,
      and static 80% compressive strain, which decreased viscosity of HD, were used to
      induce the soft state in the respective tissues. The VO(2) (in MUl/g/h) values of
      the standard state were 2.91 (CA), 1.41 (HD), and 0.56 (AD), which were less than
      1/4 of the VO(2) of the resting body-wall muscle of the starfish. The VO(2) of
      the stiff state was about 1.5 times greater than that of the standard state in
      all types of connective tissues. The VO(2) of the soft state was 3.4 (CA)-9.1
      (HD) times greater than that of the standard state. The economical nature of
      catch connective tissue in posture maintenance is discussed.

PMID- 22589406
TI  - Lobster (Panulirus argus) hepatopancreatic trypsin isoforms and their digestion
      efficiency.
AB  - It is well known that crustaceans exhibit several isoforms of trypsin in their
      digestive system. Although the number of known crustacean trypsin isoforms
      continues increasing, especially those derived from cDNA sequences, the role of
      particular isoenzymes in digestion remains unknown. Among invertebrates,
      significant advances in the understanding of the role of multiple trypsins have
      been made only in insects. Since it has been demonstrated that trypsin isoenzyme
      patterns (phenotypes) in lobster differ in digestion efficiency, we used this
      crustacean as a model for assessing the biochemical basis of such differences. We
      demonstrated that the trypsin isoform known to be present in all individuals of
      Panulirus argus has a high catalytic efficiency (k(cat)/K(m) ) and is the most
      reactive toward native proteinaceous substrates, whereas one of the isoforms
      present in less efficient individuals has a lower k(cat) and a lower k(cat)/K(m),
      and it is less competent at digesting native proteins. A fundamental question in
      biology is how genetic differences produce different physiological performances.
      This work is the first to demonstrate that trypsin phenotypic variation in
      crustacean protein digestion relies on the biochemical properties of the
      different isoforms. Results are relevant for understanding trypsin polymorphism
      and protein digestion in lobster.

PMID- 22589408
TI  - Validity of a brief interview for assessing reflective function.
AB  - The Reflective Function Scale was developed by Fonagy and colleagues (1998) to
      empirically measure the capacity to mentalize thoughts, intentions, feelings, and
      beliefs about oneself and others. Reflective Function (RF) has been reliably
      measured by the Adult Attachment Interview (AAI; Main and Goldwyn 1998), but its
      length (45-90 minutes) and the labor required to administer, transcribe, and code
      for RF may be prohibitive for many research studies. The present study measured
      the reliability and validity of the Brief Reflective Function Interview (BRFI;
      Rudden, Milrod, and Target 2005) by administering it to 27 undergraduate
      participants previously assessed using the AAI in another research study
      (Morrison 2010). The BRFI was coded reliably by two independent raters (ICC =
      .79) and yielded a highly significant positive correlation (r = .71) between RF
      scores obtained by BRFI and by AAI. The average administration time of the BRFI
      (M = 24.15 minutes) was significantly shorter than that of the AAI (M = 44.65
      minutes). These findings suggest that the BRFI may offer a reliable, valid, and
      streamlined alternative to the AAI as a measure for coding RF.

PMID- 22589409
TI  - Analysis of gene expression regulated by the ETV5 transcription factor in OV90
      ovarian cancer cells identifies FOXM1 overexpression in ovarian cancer.
AB  - Epithelial ovarian cancer is the most lethal gynecologic malignancy and the fifth
      leading cause of cancer death in women in the Western world. ETS transcription
      factors have been implicated in the regulation of gene expression during a
      variety of biologic processes including cell growth and differentiation. We
      recently examined the role of the ETS transcription factor ETV5 in epithelial
      ovarian cancer and described ETV5 as being upregulated in ovarian tumor samples
      as compared with ovarian tissue controls. In ovarian cancer cells, we showed that
      ETV5 regulated the expression of cell adhesion molecules, enhancing ovarian
      cancer cell survival in anchorage-independent conditions and suggesting that it
      plays a role in ovarian cancer cell dissemination and metastasis into the
      peritoneal cavity. To understand the role of ETV5 transcription factor during
      ovarian cancer cell dissemination, we analyzed by gene expression microarray
      technology those genes whose expression was altered in an ovarian cancer cell
      line with a stable downregulation of ETV5. The analysis of the genes and
      signaling pathways under the control of ETV5 in OV90 cells has unraveled new
      signaling pathways that interact with ETV5, among them the cell-cycle progression
      and the TGFbeta signaling pathway. In addition, we found that the downregulation
      of ETV5 reduced the expression of the oncogenic transcription factor FOXM1.
      Consistently, FOXM1 was overexpressed in ovarian tumor samples, and its
      transcriptional levels increased with ETV5 transcription in ovarian tumor
      samples. Moreover, FOXM1 expression levels increased with tumor grade, suggesting
      a role in the progression of ovarian cancer.

PMID- 22589410
TI  - FES kinase promotes mast cell recruitment to mammary tumors via the stem cell
      factor/KIT receptor signaling axis.
AB  - KIT receptor is required for mast cell development, survival, and migration
      toward its ligand stem cell factor (SCF). Many solid tumors express SCF and this
      leads to mast cell recruitment to tumors and release of mediators linked to tumor
      angiogenesis, growth, and metastasis. Here, we investigate whether FES protein
      tyrosine kinase, a downstream effector of KIT signaling in mast cells, is
      required for migration of mast cells toward SCF-expressing mammary tumors. Using
      a novel agarose drop assay for chemotaxis of bone marrow-derived mast cells
      (BMMC) toward SCF, we found that defects in chemotaxis of fes-null BMMCs
      correlated with disorganized microtubule networks in polarized cells. FES
      displayed partial colocalization with microtubules in polarized BMMCs and has at
      least two direct microtubule binding sites within its N-terminal F-BAR and SH2
      domains. An oligomerization-disrupting mutation within the Fer/CIP4 homology
      Bin/Amphiphysin/Rvs (F-BAR) domain had no effect on microtubule binding, whereas
      microtubule binding to the SH2 domain was dependent on the phosphotyrosine
      binding pocket. FES involvement in mast cell recruitment to tumors was tested
      using the AC2M2 mouse mammary carcinoma model. These tumor cells expressed SCF
      and promoted BMMC recruitment in a KIT- and FES-dependent manner. Engraftment of
      AC2M2 orthotopic and subcutaneous tumors in control or fes-null mice, revealed a
      key role for FES in recruitment of mast cells to the tumor periphery. This may
      contribute to the reduced tumor growth and metastases observed in fes-null mice
      compared with control mice. Taken together, FES is a potential therapeutic target
      to limit the progression of tumors with stromal mast cell involvement.

PMID- 22589411
TI  - An interpersonal analysis of pathological personality traits in DSM-5.
AB  - The proposed changes to the personality disorder section of the Diagnostic and
      statistical manual of mental disorders (5th ed.) places an increased focus on
      interpersonal impairment as one of the defining features of personality
      psychopathology. In addition, a proposed trait model has been offered to provide
      a means of capturing phenotypic variation on the expression of personality
      disorder. In this study, the authors subject the proposed DSM-5 traits to
      interpersonal analysis using the inventory of interpersonal problems-circumplex
      scales via the structural summary method for circumplex data. DSM-5 traits were
      consistently associated with generalized interpersonal dysfunction suggesting
      that they are maladaptive in nature, the majority of traits demonstrated
      discriminant validity with prototypical and differentiated interpersonal problem
      profiles, and conformed well to a priori hypothesized associations. These results
      are discussed in the context of the DSM-5 proposal and contemporary interpersonal
      theory, with a particular focus on potential areas for expansion of the DSM-5
      trait model.

PMID- 22589412
TI  - The "what" and the "how" of dispositional mindfulness: using interactions among
      subscales of the five-facet mindfulness questionnaire to understand its relation
      to substance use.
AB  - Although self-report measures of dispositional mindfulness have good psychometric
      properties, a few studies have shown unexpected positive correlations between
      substance use and mindfulness scales measuring observation of present-moment
      experience. The current study tested the hypothesis that the relationship between
      present-moment observation and substance use is moderated by the tendency to be
      nonjudgmental and nonreactive toward the observed stimuli. Two hundred and ninety
      six undergraduates completed the five-facet mindfulness questionnaire (FFMQ), a
      calendar measuring periods of substance use, and a measure of the five-factor
      model of personality. Controlling for FFMQ and personality subscales, significant
      interactions between the observing and nonreactivity subscales indicated that the
      observing subscale was negatively associated with substance use at higher levels
      of nonreactivity but positively associated with periods of substance use at lower
      levels of nonreactivity. Results support the use of statistical interactions
      among FFMQ subscales to test for the presence of interactive effects of different
      aspects of mindfulness.

PMID- 22589413
TI  - Many-faceted Rasch calibration: an example using the Self-Talk Scale.
AB  - The purpose of this study was to demonstrate the application of the many-faceted
      Rasch model to a personality measure. The authors use the model to calibrate the
      Self-Talk Scale (STS). Good model-data fit supported the measurement of self-talk
      frequency in adults as a unidimensional construct. Results also supported the
      proper functioning of the original five-category STS response format. Because of
      evidence that different items do not contribute equally to the total score, the
      authors provide information for converting raw STS total scores into more
      appropriate logit scores. The methodology and results demonstrate how the Rasch
      model can provide additional support for the validity of measures. Implications
      for using the Rasch model for personality assessment in general and for using the
      STS in particular are discussed.

PMID- 22589414
TI  - FTMAP: extended protein mapping with user-selected probe molecules.
AB  - Binding hot spots, protein sites with high-binding affinity, can be identified
      using X-ray crystallography or NMR by screening libraries of small organic
      molecules that tend to cluster at such regions. FTMAP, a direct computational
      analog of the experimental screening approaches, globally samples the surface of
      a target protein using small organic molecules as probes, finds favorable
      positions, clusters the conformations and ranks the clusters on the basis of the
      average energy. The regions that bind several probe clusters predict the binding
      hot spots, in good agreement with experimental results. Small molecules
      discovered by fragment-based approaches to drug design also bind at the hot spot
      regions. To identify such molecules and their most likely bound positions, we
      extend the functionality of FTMAP (http://ftmap.bu.edu/param) to accept any small
      molecule as an additional probe. In its updated form, FTMAP identifies the hot
      spots based on a standard set of probes, and for each additional probe shows
      representative structures of nearby low energy clusters. This approach helps to
      predict bound poses of the user-selected molecules, detects if a compound is not
      likely to bind in the hot spot region, and provides input for the design of
      larger ligands.

PMID- 22589415
TI  - Measurements of DNA-loop formation via Cre-mediated recombination.
AB  - The Cre-recombination system has become an important tool for genetic
      manipulation of higher organisms and a model for site-specific DNA-recombination
      mechanisms employed by the lambda-Int superfamily of recombinases. We report a
      novel quantitative approach for characterizing the probability of DNA-loop
      formation in solution using time-dependent ensemble Forster resonance energy
      transfer measurements of intra- and inter-molecular Cre-recombination kinetics.
      Our method uses an innovative technique for incorporating multiple covalent
      modifications at specific sites in covalently closed DNA. Because the mechanism
      of Cre recombinase does not conform to a simple kinetic scheme, we employ
      numerical methods to extract rate constants for fundamental steps that pertain to
      Cre-mediated loop closure. Cre recombination does not require accessory proteins,
      DNA supercoiling or particular metal-ion cofactors and is thus a highly flexible
      system for quantitatively analyzing DNA-loop formation in vitro and in vivo.

PMID- 22589416
TI  - Stochastic simulation for the inference of transcriptional control network of
      yeast cyclins genes.
AB  - Cell cycle is controlled by the activity of protein family of cyclins and cyclin
      dependent kinases that are periodically expressed during cell cycle and that are
      conserved among different species. Genome-wide location analysis found that
      cyclins are controlled by a small number of transcription factors that form
      closed network of genes controlling each other. To investigate gene expression
      dynamics of this network, we developed a general procedure for stochastic
      simulation of gene expression process. Using the binding data, we simulated gene
      expression of all genes of the network for all possible combinations of
      regulatory interactions and by statistical comparison with experimentally
      measured time series excluded those interactions that formed gene expression
      temporal profiles significantly different from the measured ones. These
      experiments led to a new definition of the cyclins regulatory network coherent
      with the binding experiments which are kinetically plausible. Level of influence
      of individual regulators in control of the regulated genes is defined. Simulation
      results indicate particular mechanism of regulatory activity of protein complexes
      involved in the control of cyclins.

PMID- 22589417
TI  - Utilizing the hair follicle to dissect the regulation and autocrine/paracrine
      activities of prolactin in humans.

PMID- 22589418
TI  - Cigarette smoking among college students: longitudinal trajectories and health
      outcomes.
AB  - INTRODUCTION: Light and intermittent patterns of cigarette smoking are prevalent
      among U.S. college-aged individuals. It is unclear whether intermittent smokers
      maintain their use over time or are transitioning to daily use or nonuse, and
      whether they experience more adverse health outcomes than nonsmokers. METHODS:
      This study examined the trajectories of tobacco cigarette smoking, their
      predictors, and health outcomes among students (N = 1,253) assessed during their
      first year of college (Y(1)) and annually thereafter (Y(2), Y(3), and Y(4)).
      RESULTS: In Y(1), 3.4% smoked daily and 4.1% exhibited signs of dependence (first
      cigarette within 30 min of waking). Growth curve modeling identified five
      distinct smoking trajectories. After stable nonsmokers (71.5%(wt)), the low
      stable smoking trajectory was the most common (13.3%(wt)), outnumbering both low
      increasing (6.5%(wt)) and high-stable smokers (5.5%(wt)) by 2:1 and high
      decreasing smokers (3.2%(wt)) by 4:1. The likelihood of maintaining a low level
      of smoking over time was inversely related to Y(1) smoking frequency. Few
      demographic, smoking, and alcohol use characteristics measured in Y(1)
      distinguished low-increasers from low-stable smokers or high-decreasers from high
      stable smokers. By Y(4), high-stable smokers rated their health significantly
      worse than all others except low-increasers. High-stable smokers had the most
      Y(4) health problems (i.e., provider visits for health problems and days of
      illness-related impairment), but only among nonWhites. CONCLUSIONS: Many college
      students smoke, but few smoke daily or are nicotine dependent. Intermittent
      smoking patterns are often stable throughout college and are associated with
      adverse health outcomes. Prevention strategies should be designed to mitigate the
      possible long-term health consequences of light and intermittent smoking.

PMID- 22589419
TI  - Bupropion and its main metabolite reverse nicotine chronic tolerance in the
      mouse.
AB  - INTRODUCTION: Although the antidepressant bupropion is prescribed to aid in
      smoking cessation, little is known concerning its mechanisms of action in this
      regard. One factor that might influence quit success is nicotine tolerance, which
      could promote high levels of nicotine intake in order to maintain nicotine's
      subjective effects (thereby making attempts to reduce smoking more difficult).
      METHODS: To explore whether bupropion and its active hydroxymetabolite modulate
      nicotine tolerance, mice were injected for 14 days with saline or nicotine. On
      Day 14, animals received saline, (2S,3S)-hydroxybupropion, or bupropion at
      different doses. On Day 15, mice were assayed on test day for nicotine-induced
      analgesia and hypothermia. RESULTS: Animals chronically injected with saline +
      nicotine developed tolerance to nicotine's effects in both assays. Administration
      of bupropion and (2S,3S)-hydroxybupropion dose-dependently reversed chronic
      nicotine tolerance. CONCLUSIONS: These results indicate that bupropion's ability
      to promote smoking cessation may be partly due to its attenuation of nicotine
      tolerance since both measured responses of nicotine (antinociception and
      hypothermia) are mediated to a large extent by neuronal alpha4beta2* nicotine
      receptors.

PMID- 22589420
TI  - Indoor air pollution levels were halved as a result of a national tobacco ban in
      a New Zealand prison.
AB  - INTRODUCTION: Few studies have measured the effect of tobacco bans on secondhand
      smoke (SHS) exposure in prisons. From June 1, 2011, the sale of tobacco was
      prohibited in New Zealand prisons. One month later, the possession of tobacco was
      banned. We studied the indoor air quality before and after this policy was
      enforced. METHODS: We measured indoor-fine-particulate (PM(2.5)) concentrations
      using a TSI SidePak photometer. The instrument was placed in a staff base of a
      New Zealand maximum-security prison, adjacent to four 12-cell wings. Measurements
      were made before the sales restriction, during this period, and after the ban.
      Data were summarized using daily geometric means and generalized least squares
      regression. RESULTS: A total of 7,107 observations were recorded at 5-min
      intervals, on 14 days before and 15 days after implementation, between 24 May and
      5 August. Before the policy was implemented, the geometric mean was 6.58 MUg/m(3)
      (95% CI = 6.29-6.58), which declined to 5.17 MUg/m(3) (95% CI = 4.93-5.41) during
      the sales ban, and fell to 2.44 MUg/m(3) (95% CI = 2.37-2.52) after the smoking
      ban. Regression analyses revealed an average 57% (95% CI = 42-68) decline in
      PM(2.5) concentrations, comparing the before and after periods. CONCLUSIONS: Our
      study showed a rapid and substantial improvement in indoor air quality after
      tobacco was banned at a prison. We conclude that prisoners have reduced their
      smoking in line with the ban, and that a significant health hazard has been
      reduced for staff and prisoners alike.

PMID- 22589421
TI  - Safety of varenicline among smokers enrolled in the lung HIV study.
AB  - INTRODUCTION: The prevalence of smoking is high among the human immunodeficiency
      virus (HIV)-infected population, yet there are few studies of tobacco dependence
      treatment in this population. This paper reports the safety of varenicline versus
      nicotine replacement therapy (NRT) and describes preliminary results about the
      effectiveness of varenicline versus NRT in HIV-infected smokers. METHODS:
      Participants completed 12 weeks of telephone counseling and either varenicline or
      NRT. Varenicline was encouraged as the preferred intervention; NRT was used for
      those unable/unwilling to take varenicline. Adverse events (AEs), related to
      pharmacotherapy, were monitored. Biochemically confirmed abstinence at 3 months
      was examined. Inverse probability of treatment weighted logistic regression
      models was fit to compare participants on varenicline to those on NRT. RESULTS:
      Among participants on varenicline (n = 118), the most common AEs were nausea,
      sleep problems, and mood disturbances. One person reported suicidal ideation;
      there were no cardiovascular complications. There were no differences in the
      varenicline AE profile between participants on combination antiretroviral therapy
      (ART) and those not on ART. The percentages of confirmed abstainers were 11.8% in
      the NRT group and 25.6% in the varenicline group. The odds of being abstinent
      were 2.54 times as great in the varenicline group compared with the NRT group in
      the propensity weighted model (95% CI 1.43-4.49). CONCLUSIONS: In this
      preliminary study, the safety profile of varenicline among HIV-infected smokers
      resembles findings among smokers without HIV. In addition, varenicline may be
      more effective at promoting abstinence in this population. Future randomized
      clinical trials are warranted.

PMID- 22589422
TI  - Smoking characteristics and comorbidities in the power to quit randomized
      clinical trial for homeless smokers.
AB  - INTRODUCTION: Smoking prevalence in homeless populations is strikingly high
      (~70%); yet, little is known about effective smoking cessation interventions for
      this population. We conducted a community-based clinical trial, Power To Quit
      (PTQ), to assess the effects of motivational interviewing (MI) and nicotine patch
      (nicotine replacement therapy [NRT]) on smoking cessation among homeless smokers.
      This paper describes the smoking characteristics and comorbidities of smokers in
      the study. METHODS: Four hundred and thirty homeless adult smokers were
      randomized to either the intervention arm (NRT + MI) or the control arm (NRT +
      Brief Advice). Baseline assessment included demographic information, shelter
      status, smoking history, motivation to quit smoking, alcohol/other substance
      abuse, and psychiatric comorbidities. RESULTS: Of the 849 individuals who
      completed the eligibility survey, 578 (68.1%) were eligible and 430 (74.4% of
      eligibles) were enrolled. Participants were predominantly Black, male, and had
      mean age of 44.4 years (S  D = 9.9), and the majority were unemployed (90.5%).
      Most participants reported sleeping in emergency shelters; nearly half had been
      homeless for more than a year. Nearly all the participants were daily smokers who
      smoked an average of 20 cigarettes/day. Nearly 40% had patient health
      questionnaire-9 depression scores in the moderate or worse range, and more than
      80% screened positive for lifetime history of drug abuse or dependence.
      CONCLUSIONS: This study demonstrates the feasibility of enrolling a diverse
      sample of homeless smokers into a smoking cessation clinical trial. The
      uniqueness of the study sample enables investigators to examine the influence of
      nicotine dependence as well as psychiatric and substance abuse comorbidities on
      smoking cessation outcomes.

PMID- 22589423
TI  - High dose transdermal nicotine for fast metabolizers of nicotine: a proof of
      concept placebo-controlled trial.
AB  - INTRODUCTION: Smokers with a faster rate of nicotine metabolism, estimated using
      the ratio of 3'-hydroxycotinine (3-HC) to cotinine, have lower plasma nicotine
      levels and are more likely to relapse with 21 mg nicotine patch therapy, than
      smokers with slower rates of nicotine metabolism. Thus, faster metabolizers of
      nicotine may require a higher nicotine patch dose to achieve cessation. METHODS:
      This proof of concept randomized placebo-controlled trial evaluated the efficacy
      and safety of 8 weeks of 42 mg transdermal nicotine versus 21 mg, among 87 fast
      metabolizers of nicotine (3-HC/cotinine >= 0.18). RESULTS: After 1 week of
      treatment, an intent-to-treat (ITT) analysis showed that participants treated
      with 42 mg nicotine had significantly higher expired-air carbon monoxide (CO)
      confirmed 24-hr abstinence (75% vs. 58.1%; OR = 3.21; 95% CI: 1.12-9.24, p = .03)
      but not 7-day abstinence (50% vs. 34.9%; OR = 2.02; 95% CI: 0.82-4.94, p = .13).
      After 8 weeks of treatment, ITT analysis showed that participants treated with 42
      mg nicotine had marginally higher rates of CO-confirmed 24-hr abstinence (45.5%
      vs. 30.2%; OR = 2.32; 95% CI: 0.92-5.92, p = .08) but not 7-day abstinence (29.6%
      vs. 23.3%; OR = 1.52, 95% CI: 0.57-4.07, p = .41). Percent nicotine and cotinine
      replacement were significantly greater for 42 mg nicotine versus 21 mg (p <
      .005). There were no significant differences between treatment arms in the
      frequency of severe side effects and serious adverse events or blood pressure
      during treatment (p > .10). CONCLUSIONS: Further examination of the efficacy of
      42 mg nicotine patch therapy for fast metabolizers of nicotine is warranted.

PMID- 22589424
TI  - Differences between Latino daily light and heavier smokers in smoking attitudes,
      risk perceptions, and smoking cessation outcome.
AB  - INTRODUCTION: Daily light smoking is increasing and disproportionately
      represented among Latinos. The current study examines differences in smoking
      attitudes, psychosocial characteristics, risk perceptions, and cessation rates
      between Latino daily light (3-9 cigarettes/day) and heavier smokers (>= 10
      cigarettes/day). METHODS: Participants (N = 131; M(age) = 36.8, 73.3% female,
      53.1% light smokers) were enrolled in a study focused on motivating smokers to
      quit. Cessation was biochemically verified at 2 and 3 months after end of
      treatment. RESULTS: Heavier smoking was more prevalent among males (65.7%) and
      those from Puerto Rico (69.0%). Compared with heavier smokers, light smokers were
      less nicotine dependent (p < .001), reported fewer pros of smoking (p <= .001),
      less perceived stress (p <= .001), had fewer friends who smoked (p <= .005), were
      more likely to live in a household with an indoor smoking ban (p <= .001), and
      self-reported better health (p < .05). Regarding risk perceptions, Latino light
      smokers reported less perceived vulnerability for the health effects from smoking
      on their child's health (p < .05). There were no significant differences in
      smoking cessation rates between daily light and heavier smokers at either 2- or 3
      month follow-up. Belief that quitting would improve "their own health," however,
      significantly predicted smoking cessation at both 2- and 3-month follow-up, but
      only among heavier smokers. CONCLUSIONS: Latino light smokers do not seem to be
      more likely to quit smoking than Latinos who smoke at heavier rates. Differences
      between Latino light and heavier smokers in demographics, smoking attitudes, and
      psychosocial factors may need to be considered when developing cessation programs
      and mass media campaigns. Future research should continue to explore whether
      Latino light smokers need different or more targeted treatments.

PMID- 22589425
TI  - Effects of cigarette smoke exposure and its cessation on body weight, food intake
      and circulating leptin, and ghrelin levels in the rat.
AB  - INTRODUCTION: Smoking is associated with loss of body weight (BW) and reduced
      appetite, while smoking abstinence with the opposite effect. The role of
      peripheral signaling by appetite-controlling hormones leptin and ghrelin is not
      clear. In the present study, the relationship of circulating leptin and ghrelin
      with BW and food intake rate (FIR) changes was studied during cigarette smoke
      exposure (CSE) and after its cessation in the rat. METHODS: Male Wistar rats were
      subjected to CSE for 8 weeks by confinement to plexiglass chambers (Group S).
      Control animals were confined to identical chambers without smoke (Group C).
      During CSE and an equivalent follow-up period, BW and FIR was recorded and serum
      leptin and ghrelin levels were measured. RESULTS: A sharp decrease in BW was
      noted during the first 4 weeks of CSE, while FIR, after a substantial decrease
      noted at Week 1, returned to control levels. Thereafter, rats started to regain
      their BW until they reached control levels by the 1st week postCSE. BW regain was
      accompanied by a rebound increase of FIR, which plateaued during the first 4
      weeks postCSE and then normalized. Serum leptin was decreased in Group S during
      both periods, normalizing at the 7th week postCSE. Ghrelin levels did not differ
      between groups. CONCLUSIONS: Circulating leptin could not explain by its own BW
      and FIR changes during the first few week of CSE in rats, in contrast to the rest
      of the CSE period as well as after its cessation. Serum ghrelin levels did not
      justify BW and FIR changes.

PMID- 22589426
TI  - Psychometric properties of the Five Facets Mindfulness Questionnaire (FFMQ) in a
      meditating and a non-meditating sample.
AB  - The factor structure, internal consistency, construct validity, and predictive
      validity of the Dutch version of the Five Facet Mindfulness Questionnaire (FFMQ
      NL) were studied in a sample of meditators (n = 288) and nonmeditators (n = 451).
      A five-factor structure was demonstrated in both samples, and the FFMQ-NL and its
      subscales were shown to have good internal consistencies. Meditators scored
      higher on all facets of the FFMQ-NL than the participants in the nonmeditating
      sample. For both samples, expected negative correlations between most mindfulness
      facets (all except for the Observing facet) and the constructs of alexithymia,
      thought suppression, rumination, worry, and dissociation were found. The
      Observing facet of the FFMQ-NL showed an unexpected positive correlation with
      thought suppression in the nonmeditating sample. Furthermore, as expected,
      mindfulness facets were negatively related to psychological symptoms, and all
      mindfulness facets except for Observing and Describing significantly predicted
      psychological symptoms. Overall, the Dutch FFMQ demonstrated favorable
      psychometric properties, commensurate with its (original) English language
      version.

PMID- 22589427
TI  - Involvement of glial cells in the autoregulation of optic nerve head blood flow
      in rabbits.
AB  - PURPOSE: To investigate the involvement of glial cells in the autoregulation of
      optic nerve head (ONH) blood flow in response to elevated intraocular pressure
      (IOP). METHODS: Rabbit eyes were treated with an intravitreal injection of l-2
      aminoadipic acid (LAA), a gliotoxic compound. Twenty-four hours after the
      injection IOP was artificially elevated from a baseline of 20 to 50 or 70 mm Hg
      and maintained at each IOP level for 30 minutes. ONH blood flow was measured by
      laser speckle flowgraphy every 10 minutes. Ocular perfusion pressure (OPP) was
      calculated to investigate the relationship between ONH blood flow and OPP. To
      evaluate the effects of LAA on the function and morphology of retinal neurons and
      glial cells, electroretinogram (ERG) was monitored after injections of LAA (2.0
      and 6.0 mM) or saline as a control. Histologic and immunohistochemical
      examinations were then performed. RESULTS: In the LAA-treated eyes, histologic
      changes selectively occurred in the retinal Muller cells and ONH astrocytes.
      There was not any significant reduction of amplitude or elongation of implicit
      time of each parameter in the ERG after LAA injection compared with control. ONH
      blood flow in LAA-treated eyes was significantly decreased with a reduction of
      OPP during IOP elevation to 50 and 70 mm Hg, whereas blood flow was maintained in
      control eyes during IOP elevation to 50 mm Hg. CONCLUSIONS: These results
      indicate the involvement of glial ells in the autoregulation of ONH blood flow
      during IOP elevation.

PMID- 22589428
TI  - Structural and functional abnormalities of retinal ganglion cells measured in
      vivo at the onset of optic nerve head surface change in experimental glaucoma.
AB  - PURPOSE: To compare peripapillary retinal nerve fiber layer thickness (RNFLT),
      RNFL retardance, and retinal function at the onset of optic nerve head (ONH)
      surface topography change in experimental glaucoma (EG). METHODS: Thirty-three
      rhesus macaques had three or more weekly baseline measurements in both eyes of
      ONH surface topography, peripapillary RNFLT, RNFL retardance, and multifocal
      electroretinography (mfERG). Laser photocoagulation was then applied to the
      trabecular meshwork of one eye to induce chronic elevation of IOP and weekly
      recordings continued alternating between ONH surface topography and RNFLT during
      one week and RNFL retardance and mfERG the next week. Data were pooled for the
      group at the onset of ONH surface topography change in each EG eye, which was
      defined as the first date when either the mean position of the disc (MPD) fell
      below the 95% confidence limit of each eye's individual baseline range and/or
      when the topographic change analysis (TCA) map was subjectively judged as having
      demonstrated change, whichever came first. Analysis of variance with post hoc
      tests corrected for multiple comparisons were used to assess parameter changes.
      RESULTS: At onset of ONH surface topography change, there was no significant
      difference for RNFLT versus baseline or fellow control eyes. RNFL retardance and
      mfERG were significantly reduced in the recordings just prior (median of 9 days)
      to ONH onset (P < 0.01) and had progressed significantly (P < 0.001) an average
      of 17 days later (median of 7 days after ONH onset). RNFLT did not exhibit
      significant thinning until 15 days after onset of ONH surface topography change
      (P < 0.001). CONCLUSIONS: These results support the hypothesis that during the
      course of glaucomatous neurodegeneration, axonal cytoskeletal and retinal
      ganglion cell functional abnormalities exist before thinning of peripapillary
      RNFL axon bundles begins.

PMID- 22589430
TI  - Simultaneous analysis of multiple cytokines in the vitreous of patients with
      sarcoid uveitis.
AB  - PURPOSE: Levels of some cytokines are significantly higher in the vitreous fluid
      of patients with acute uveitis than in normal vitreous fluid. The authors sought
      to determine which proinflammatory cytokines were upregulated in the vitreous
      fluid of patients with ocular sarcoidosis. METHODS: Samples of vitreous fluid
      were collected from patients with sarcoid uveitis and from nonsarcoid control
      patients with idiopathic epiretinal membrane. The levels of 27 proinflammatory
      cytokines were measured with a multiplex beads array system. Postvitrectomy
      macular thickness was also measured by using spectral domain optical coherence
      tomography (SD-OCT). To assess the relationship between cytokine levels and
      disease stage, the authors divided patients into three groups based on macular
      thickness 1 month after operation. RESULTS: The vitreous levels of 17 cytokines
      were significantly higher in patients with ocular sarcoidosis than in nonsarcoid
      controls. Serum levels of interferon gamma-induced protein 10 (IP-10) were also
      higher in ocular sarcoidosis patients than in nonsarcoid controls. Conversely,
      serum levels of interleukin (IL) 15 in ocular sarcoidosis patients were lower
      than in the control group. Analysis of cytokine levels and macular thickness
      revealed that IL-1ra, IL-4, IL-8, IFN-gamma, IP-10, monocyte chemotactic protein
      (MCP)-1, macrophage inflammatory protein (MIP)-1beta, and regulated on
      activation, normal T-cell expressed and secreted (RANTES) were significantly
      upregulated in patients with thin cystoid macular edema group. CONCLUSIONS:
      Patients with ocular sarcoidosis had elevated levels of proinflammatory cytokines
      in vitreous fluids. Different cytokines might contribute to different stages of
      macular edema.

PMID- 22589429
TI  - Anisometropia in children from infancy to 15 years.
AB  - PURPOSE: To investigate anisometropia in children from age 6 months to 15 years.
      METHODS: Children with refractions at 6 months (n = 1120), 5 years (n = 395), and
      12 to 15 years (n = 312) were included in this study. All children were refracted
      in the laboratory by noncycloplegic retinoscopy. Myopes had spherical equivalent
      refraction (SER) of the less ametropic eye of less than -0.50 D, hyperopes had
      SER of the less ametropic eye greater than or equal to 1.00 D, and emmetropes had
      SER of the less ametropic eye from -0.50 to +1.00 D. RESULTS: The mean difference
      in refraction between the two eyes was similar at 6 months (0.11 D) and 5 years
      (0.15 D), increasing to 0.28 D at 12 to 15 years. Using a cutoff of 1.00 D SER
      for anisometropia, the prevalence was 1.96%, 1.27%, and 5.77% at 6 months, 5
      years, and 12 to 15 years, respectively. At 12 to 15 years, the prevalence of
      anisometropia in the myopes was 9.64% and in the hyperopes was 13.64%, both
      significantly higher than that in the emmetropes (3.38%, P < 0.05). The degree of
      anisometropia at 12 to 15 years was significantly associated with the refractive
      error of the less ametropic eye at 12 to 15 years, with and without adjustment
      for relevant covariates (P < 0.05). Infants with significant astigmatism
      (cylinder power >= 1.00 D in one or both eyes) have an increased risk of
      anisometropia (P < 0.05). CONCLUSIONS: The prevalence of anisometropia increases
      between 5 and 15 years, when some children's eyes grow longer and become myopic.
      However, anisometropia was found to accompany both myopia and hyperopia,
      suggesting that other mechanisms in addition to excessive eye growth may exist
      for anisometropia development, especially in hyperopia.

PMID- 22589431
TI  - Invasion of lymphatic vessels into the eye after open globe injuries.
AB  - PURPOSE: We analyzed whether lymphatic vessels can be detected in eyes enucleated
      after an open globe injury. METHODS: The presence of lymphatic vessels was
      analyzed immunohistochemically using podoplanin as a specific lymphatic
      endothelial marker in 21 globes that had been enucleated after open globe injury.
      The localization of pathologic lymphatic vessels (within the eye wall or inside
      the eye) was correlated with the mechanism of trauma, anatomic site of
      perforation or rupture, and time interval between trauma and enucleation.
      RESULTS: Pathologic lymphatic vessels were detected in 15 of 21 eyes (71%)
      enucleated after an open globe injury. In 5 globes (24%) they were found within
      the eye, located in retrocorneal membranes, underneath the sclera, and adjacent
      to uveal tissue (ciliary body, iris). No significant association was observed
      between the presence of pathologic lymphatic vessels and the mechanism of trauma
      (P = 0.598), anatomic site of perforation or rupture (P = 0.303), and time
      interval between trauma and enucleation (P = 0.145). CONCLUSIONS: The human eye
      can be invaded secondarily by lymphatic vessels if the eye wall is opened by
      trauma. This mechanism could be important for wound healing, immunologic defense
      against intruding microorganisms, and autoimmune reactions against intraocular
      antigens.

PMID- 22589432
TI  - Time course of changes in metamorphopsia, visual acuity, and OCT parameters after
      successful epiretinal membrane surgery.
AB  - PURPOSE: To follow the changes in the metamorphopsia, visual acuity, and OCT
      parameters after epiretinal membrane (ERM) removal. METHODS: The study included
      49 eyes of 49 patients with an ERM who underwent vitrectomy and membrane peeling.
      The changes in the best-corrected visual acuity (BCVA), metamorphopsia, and
      central foveal thickness (CFT) were evaluated at baseline and 1, 3, 6, 9, and 12
      months postoperatively. M-CHARTS were used to quantify metamorphopsia. RESULTS:
      The mean BCVA, metamorphopsia scores for horizontal lines (MH) and vertical lines
      (MV), and CFT improved significantly at 12 months after surgery (P < 0.001). The
      baseline BCVA, MH score, and MV score were significantly correlated with the
      corresponding BCVA, MH score, and MV score at 12 months after surgery (P < 0.01).
      The MH and MV scores at 12 months was significantly correlated with the BCVA at
      12 months (P < 0.01), and the baseline MV score was significantly correlated with
      the BCVA at 12 months (P < 0.05). The MH score but not the MV score was
      significantly correlated with the CFT at baseline and 12 months (P < 0.05).
      CONCLUSIONS: The preoperative BCVA, MH score, and MV score were prognostic
      factors for the corresponding postoperative BCVA, MH score, and MV score. These
      results suggest that surgery for ERM should be considered before severe reduction
      in the BCVA or the degree of metamorphopsia. In addition, the preoperative MV
      score was a prognostic factor for postoperative BCVA. The MH score but not the MV
      score was correlated with the CFT preoperatively and postoperatively.

PMID- 22589433
TI  - Morphologic analysis in pathologic myopia using high-penetration optical
      coherence tomography.
AB  - PURPOSE: We evaluated retrospectively the morphologic choroidal and scleral
      characteristics in eyes with pathologic myopia using high-penetration optical
      coherence tomography (HP-OCT) or swept-source OCT (SS-OCT). METHODS: The
      subfoveal choroidal and scleral thicknesses were measured using the prototype HP
      OCT with a 1060 nm light source. We also measured the scleral thickness 3 mm
      superior, inferior, nasal, and temporal to the fovea on the horizontal and
      vertical OCT sections. The axial length (AL) in all eyes was measured using
      optical biometry. RESULTS: We examined 58 eyes of 35 patients (7 men and 28
      women, mean age 65.5 years) with an AL exceeding 26.5 mm. The mean AL was 29.0 +/
      1.4 mm. The full-thickness choroid and sclera were visualized in all eyes. The
      mean subfoveal choroidal and scleral thicknesses were 52 +/- 38 and 335 +/- 130
      MUm, respectively. The mean scleral thicknesses 3 mm superior, inferior, nasal,
      and temporal to the fovea were 266 +/- 78 (n = 57), 259 +/- 72 (n = 56), 324 +/-
      109 (n = 39), and 253 +/- 79 (n = 58) MUm, respectively. The subfoveal sclera was
      thicker than 3 mm outside the fovea (P < 0.05, for each comparison). CONCLUSIONS:
      The full-thickness choroid and sclera in all eyes with pathologic myopia were
      visualized using a prototype HP-OCT. The subfoveal sclera was thicker than 3 mm
      outside the fovea. HP-OCT is a useful tool for morphologic analyses of pathologic
      myopia.

PMID- 22589434
TI  - Fibrinogen, riboflavin, and UVA to immobilize a corneal flap--conditions for
      tissue adhesion.
AB  - PURPOSE: Laser-assisted in situ keratomileus (LASIK) creates a permanent flap
      that remains non-attached to the underlying laser-modified stroma. This lack of
      permanent adhesion is a liability. To immobilize a corneal flap, a protocol using
      fibrinogen (FIB), riboflavin (RF), and ultraviolet (UVA) light (FIB+RF+UVA) was
      devised to re-adhere the flap to the stroma. METHODS: A model flap was created
      using rabbit (Oryctolagus cuniculus) and shark (Squalus acanthias) corneas.
      Solutions containing FIB and RF were applied between corneal strips as glue.
      Experimental corneas were irradiated with long wavelength (365 nm) UVA. To
      quantify adhesive strength between corneal strips, the glue-tissue interface was
      subjected to a constant force while a digital force gauge recorded peak tension.
      RESULTS: In the presence of FIB, substantive non-covalent interactions occurred
      between rabbit corneal strips. Adhesiveness was augmented if RF and UVA also were
      applied, suggesting formation of covalent bonds. Additionally, exposing both
      sides of rabbit corneas to UVA generated more adhesion than exposure from one
      side, suggesting that RF in the FIB solution catalyzes formation of covalent
      bonds at only the interface between stromal molecules and FIB closest to the UVA.
      In contrast, in the presence of FIB, shark corneal strips interacted non
      covalently more substantively than those of rabbits, and adhesion was not
      augmented by applying RF+UVA, from either or both sides. Residual RF could be
      rinsed away within 1 hour. CONCLUSIONS: Glue solution containing FIB and RF,
      together with UVA treatment, may aid immobilization of a corneal flap,
      potentially reducing risk of flap dislodgement.

PMID- 22589435
TI  - Multifocal intraocular lens differentiation using defocus curves.
AB  - PURPOSE: To determine the most appropriate analysis technique for the
      differentiation of multifocal intraocular lens (MIOL) designs by using defocus
      curve assessment of visual capability. METHODS: Four groups of 15 subjects were
      implanted bilaterally with either monofocal intraocular lenses, refractive MIOLs,
      diffractive MIOLs, or a combination of refractive and diffractive MIOLs. Defocus
      curves between -5.0 D and +1.5 D were evaluated by using an absolute and relative
      depth-of-focus method, the direct comparison method, and a new "area-of-focus"
      metric. The results were correlated with a subjective perception of near and
      intermediate vision. RESULTS: Neither depth-of-focus method of analysis was
      sensitive enough to differentiate between MIOL groups (P > 0.05). The direct
      comparison method indicated that the refractive MIOL group performed better at
      +1.00 diopter (D), -1.00 D, and -1.50 D and worse at -3.00 D, -3.50 D, -4.00 D,
      and -5.00 D than did the diffractive MIOL group (P < 0.05). The area-of-focus
      intermediate zone was greater with the refractive than with the diffractive MIOL
      group (P = 0.005) and the near zone was better with the diffractive (P = 0.020)
      and "mix and match" (P = 0.039) groups than with the refractive MIOL group. The
      subjective perception of intermediate and near vision agreed best with the area
      of-focus metric for the intermediate (r(s) = 0.408, P = 0.010) and near zone
      (r(s) = 0.484, P < 0.001). CONCLUSIONS: Conventional depth-of-focus metrics
      provide a single value to quantify the useful range of vision; however, they fail
      to provide sufficient detail to differentiate between MIOL designs. The direct
      comparison method provides a large amount of information, although the results
      can be complex to interpret. The proposed area-of-focus metric provides a simple,
      but differentiating method of evaluating MIOL defocus curves.

PMID- 22589437
TI  - ER stress is involved in T17M rhodopsin-induced retinal degeneration.
AB  - PURPOSE: The human rhodopsin (Rho) mutation T17M leads to autosomal dominant
      retinitis pigmentosa (adRP). The goal of our study was to elucidate the role of
      endoplasmic reticulum (ER) stress in retinal degeneration in hT17M Rho mice and
      identify potential candidates for adRP gene therapy. METHODS: We used transgenic
      mice expressing the ER stress-activated indicator (ERAI) and hT17M Rho to
      evaluate the activation of ER stress responses. Quantitative reverse
      transcription PCR (qRT-PCR) was used to analyze changes in the expression of 30
      unfolded protein response (UPR)-associated genes at P12, 15, 18, 21, and 25. The
      cytosolic fraction of hT17M Rho retinal cells was used to measure the release of
      cytochrome C and apoptotic inducing factor-1 (AIF1) by Western blotting. Optical
      coherence tomography (OCT) analysis was performed for 1-month-old hT17M Rho mice.
      RESULTS: hT17M Rho was localized in the outer nuclear layer (ONL) of T17M(+/
      )ERAI(+/-) photoreceptors as well as C57BL/6 retinas injected with AAV-hT17M Rho
      GFP. In P15 hT17M Rho retinas, we observed an up-regulation of UPR genes (Atf4,
      Eif2alpha, Xbp1, Bip, Canx, and Hsp90), autophagy genes and proapoptotic Bcl2
      genes. OCT, and the downregulation of Nrl and Crx gene expression confirmed that
      cell death occurs in 55% of photoreceptors via the up-regulation of caspase-3 and
      caspase-12, and the release of AIF1 from the mitochondria. CONCLUSIONS: The ER
      stress response is involved in retinal degeneration in hT17M Rho mice. The final
      demise of photoreceptors occurs via apoptosis involving ER stress-associated and
      mitochondria-induced caspase activation. We identified Atg5, Atg7, Bax, Bid, Bik,
      and Noxa as potential therapeutic targets for adRP treatment.

PMID- 22589436
TI  - Oral minocycline for the treatment of diabetic macular edema (DME): results of a
      phase I/II clinical study.
AB  - PURPOSE: Inflammation contributes significantly to the pathogenesis of diabetic
      macular edema (DME). In particular, retinal microglia demonstrate increased
      activation and aggregation in areas of DME. Study authors investigated the safety
      and potential efficacy of oral minocycline, a drug capable of inhibiting
      microglial activation, in the treatment of DME. METHODS: A single-center,
      prospective, open-label phase I/II clinical trial enrolled five participants with
      fovea-involving DME who received oral minocycline 100 mg twice daily for 6
      months. Main outcome measurements included best-corrected visual acuity (BCVA),
      central retinal subfield thickness (CST), and central macular volume using
      spectral domain optical coherence tomography (SD-OCT) and late leakage on
      fluorescein angiography (FA). RESULTS: Findings indicated that the study drug was
      well tolerated and not associated with significant safety issues. In study eyes,
      mean BCVA improved continuously from baseline at 1, 2, 4, and 6 months by +1.0,
      +4.0, +4.0, and +5.8 letters, respectively, while mean retinal thickness (CST) on
      OCT decreased by -2.9%, -5.7%, -13.9, and -8.1% for the same time points. At
      month 6, mean area of late leakage on FA decreased by -34.4% in study eyes. Mean
      changes in contralateral fellow eyes also demonstrated similar trends.
      Improvements in outcome measures were not correlated with concurrent changes in
      systemic factors. CONCLUSIONS: In this pilot proof-of-concept study of DME,
      minocycline as primary treatment was associated with improved visual function,
      central macular edema, and vascular leakage, comparing favorably with historical
      controls from previous studies. Microglial inhibition with oral minocycline may
      be a promising therapeutic strategy targeting the inflammatory etiology of DME.
      (ClinicalTrials.gov number, NCT01120899.).

PMID- 22589438
TI  - Proteomics analyses of activated human optic nerve head lamina cribrosa cells
      following biomechanical strain.
AB  - PURPOSE: To determine protein regulation following activation of human, optic
      nerve head (ONH), lamina cribrosa (LC) cells in response to mechanical strain.
      METHODS: LC cells were isolated and grown from donor tissue in specific media at
      37 degrees C and 5% CO(2) humidified incubator. Cells were grown to confluence on
      collagen I-coated flexible-bottom culture plates, rinsed with Dulbecco's
      phosphate-buffered saline, and left for 24 hours in serum-free media. They were
      subjected to 3% or 12% cyclic equiaxial stretch for 2 or 24 hours using a
      commercial strain-unit system. Control cells were serum-deprived and incubated
      without stretch for 24 hours. Nano liquid chromatography-mass spectrometry
      analysis with isobaric tags for relative and absolute quantitation labeling was
      used to determine protein regulation. RESULTS: In all, 526 proteins were
      discovered at a 95% confidence limit. Analysis of associated pathways and
      functional annotation indicated that the LC cells reacted in vitro to mechanical
      strain by activating pathways involved in protein synthesis, cellular movement,
      cell-to-cell signaling, and inflammation. These pathways indicated consistent
      major protein hubs across all stretch/time conditions involving transforming
      growth factor-beta1 (TGFbeta1), tumor necrosis factor (TNF), caspase-3 (CASP3),
      and tumor protein-p53 (p53). Among proteins of particular interest, also found in
      multiple stretch/time conditions, were bcl-2-associated athanogene 5 (BAG5),
      nucleolar protein 66 (NO66), and eukaryotic translation initiation factor 5A (eIF
      5A). CONCLUSIONS: Pathway analysis identified major protein hubs (TGFbeta1, TNF,
      CASP3, p53) and pathways all previously implicated in cellular activation and in
      the pathogenesis of glaucomatous optic neuropathy. Several specific proteins of
      interest (BAG5, NO66, eIF-5A) were identified for future investigation as to
      their role in ONH glial activation.

PMID- 22589439
TI  - Spatial correlation between hyperpigmentary changes on color fundus photography
      and hyperreflective foci on SDOCT in intermediate AMD.
AB  - PURPOSE: Macular hyperpigmentation is associated with progression from
      intermediate to advanced age-related macular degeneration (AMD). The purpose of
      this study was to accurately correlate hyperpigmentary changes with spectral
      domain optical coherence tomography (SDOCT) hyperreflective foci in eyes with non
      advanced AMD. METHODS: A prospective cross-sectional analysis of 314 eyes (314
      subjects) with intermediate AMD was performed in the multicenter Age-Related Eye
      Disease Study 2 (AREDS2) Ancillary SDOCT Study to correlate hyperpigmentary
      changes on color fundus photographs (CFP) with abnormal morphology on SDOCT.
      Spatial coregistration was performed with an automated algorithm in two
      nonoverlapping subsets of 20 study eyes, which permitted double-masked CFP and
      SDOCT grading by certified investigators. RESULTS: Macular CFP hyperpigmentation
      was significantly associated with SDOCT intraretinal hyperreflective foci in the
      314 study eyes (P < 0.001). In a substudy of 40 eyes, automated intermodality
      spatial coregistration was successfully achieved in all 136 (100%) retinal
      regions selected for CFP and SDOCT grading. In one subset of 20 study eyes, 28 of
      39 (71.8%) retinal CFP regions with hyperpigmentation were correlated with focal
      hyperreflectivity on SDOCT, versus seven of 39 (17.9%) control regions (P <
      0.001). In another subset of 20 eyes, 21 of 29 (72.4%) SDOCT regions with
      hyperreflective foci were correlated with hyperpigmentary changes on CFP, versus
      two of 29 (6.9%) control regions (P < 0.001). CONCLUSIONS: A novel algorithm
      achieves automated intermodality spatial coregistration for masked grading of
      regions selected on CFP and SDOCT. In intermediate AMD, macular hyperpigmentation
      has high spatial correlation to SDOCT hyperreflective foci and often represents
      the same anatomical lesion. (ClinicalTrials.gov number, NCT00734487.).

PMID- 22589440
TI  - Retinal vessel oxygen saturation under flicker light stimulation in patients with
      nonproliferative diabetic retinopathy.
AB  - PURPOSE: We investigated the response of retinal vessel diameters and oxygen
      saturation to flicker light stimulation of neuronal activity in patients with
      diabetic retinopathy. METHODS: We included 18 patients with nonproliferative
      diabetic retinopathy (mean age 62.2 +/- 8.3 years, diabetes type 1 in 4 patients
      and type 2 in 14, hemoglobin A1c 7.7 +/- 0.9%, duration of diabetes 24.1 +/- 9.3
      years) and 20 age-matched healthy controls (age 66.7 +/- 10.3 years). Dual
      wavelength (548 and 610 nm) fundus images were taken before and during luminance
      flicker stimulation (12.5 Hz, modulation depth > 1:25) for 90 seconds. Diameters
      (central retinal arterial [CRAE] and venous [CRVE] equivalents) and oxygen
      saturation (SO(2)) were determined, and averaged for all arterioles and venules
      in an annular area centered at the optic disk. RESULTS: Flicker light increased
      CRAE, CRVE, and venous SO(2) by 0.6 +/- 6.6%, 2.7 +/- 6.1%, and 2.0 +/- 2.4% (P <
      0.05), respectively, in the patients as well as 4.7 +/- 8.4% (P < 0.05), 8.7 +/-
      5.2% (P < 0.05), and 4.2 +/- 3.5% (P < 0.05), respectively, in the controls. The
      arterial SO(2) remained unchanged in both groups. The increase of the venous SO2
      correlated significantly (P = 0.027) with that of the CRAE. There was a trend (P
      = 0.06) for lower increase of the venous SO(2) with higher body mass index.
      CONCLUSIONS: Our results support the thesis of an impaired regulation of oxygen
      supply to the diabetic retina. Whereas in healthy subjects the stimulation of
      neuronal activity increases the vascular diameters and, subsequently, the oxygen
      supply, this increase is reduced in diabetic retinopathy. This may hint at the
      role of endothelial dysfunction in the etiology of the disease.

PMID- 22589441
TI  - Bacterial biofilm diversity in contact lens-related disease: emerging role of
      Achromobacter, Stenotrophomonas, and Delftia.
AB  - PURPOSE: Multi-species biofilms associated with contact lens cases and lenses can
      predispose individuals to contact lens-related inflammatory complications. Our
      study used culture-independent methods to assess the relationship between the
      severity of contact lens-related disease and bacteria residing in biofilms of
      contact lens cases and lenses. METHODS: Contact lens cases and lenses from 28
      patients referred to the West Virginia University Eye Institute and diagnosed as
      having mild keratitis, keratitis with focal infiltrates, or corneal ulcers were
      processed and evaluated for bacterial composition based on 16S ribosomal RNA gene
      sequencing. Cases and lenses from nine asymptomatic contact lens wearers were
      processed in a manner similar to controls. Relationships between disease
      severity, bacterial types, and bacterial diversity were evaluated statistically.
      RESULTS: Disease severity and presenting visual acuity correlated with an
      increase in the diversity of bacterial types isolated from contact lens cases. A
      significant difference also was observed in the number of bacterial types
      associated with the three clinical groups. Achromobacter, Stenotrophomonas, and
      Delftia were prevalent in all disease groups, and Achromobacter and
      Stenotrophomonas were present in one asymptomatic control. Scanning electron
      microscopy revealed that Achromobacter and Stenotrophomonas formed a biofilm on
      the surface of contact lenses. CONCLUSIONS: Culture-independent methods
      identified an association between disease severity and bacterial diversity in
      biofilms isolated from cases and lenses of patients with contact lens-related
      corneal disease. Achromobacter, Stenotrophomonas, and Delftia were predominant
      bacteria identified in our study, drawing attention to their emerging role in
      contact lens-related disease.

PMID- 22589442
TI  - Retinal ganglion cell morphology after optic nerve crush and experimental
      glaucoma.
AB  - PURPOSE: To study sequential changes in retinal ganglion cell (RGC) morphology in
      mice after optic nerve crush and after induction of experimental glaucoma.
      METHODS: Nerve crush or experimental glaucoma was induced in mice that
      selectively express yellow fluorescent protein (YFP) in RGCs. Mice were
      euthanized 1, 4, and 9 days after crush and 1, 3, and 6 weeks after induction of
      glaucoma by bead injection. All YFP-RGCs were identified in retinal whole mounts.
      Then confocal images of randomly selected RGCs were quantified for somal
      fluorescence brightness, soma size, neurite outgrowth, and dendritic complexity
      (Sholl analysis). RESULTS: By 9 days after crush, 98% of RGC axons died and YFP
      RGCs decreased by 64%. After 6 weeks of glaucoma, 31% of axons died, but there
      was no loss of YFP-RGC bodies. All crush retinas combined had significant
      decreases in neurite outgrowth parameters (P <= 0.036, generalized estimating
      equation [GEE] model) and dendritic complexity was lower than controls (P =
      0.017, GEE model). There was no change in RGC soma area after crush. In combined
      glaucoma data, the RGC soma area was larger than control (P = 0.04, GEE model).
      At 3 weeks, glaucoma RGCs had significantly larger values for dendritic structure
      and complexity than controls (P = 0.044, GEE model), but no statistical
      difference was found at 6 weeks. CONCLUSIONS: After nerve crush, RGCs and axons
      died rapidly, and dendritic structure decreased moderately in remaining RGCs.
      Glaucoma caused an increase in RGC dendrite structure and soma size at 3 weeks.

PMID- 22589444
TI  - Corneal power is correlated with anterior chamber diameter.
AB  - PURPOSE: Although corneal power and axial length are known to be inversely
      correlated, the biological determinants of corneal power are unknown. To
      elucidate this correlation further, study authors investigated the relationships
      among corneal power, corneal diameter, anterior chamber diameter, and axial
      length in a sample of human adults. METHODS: The eyes of 61 subjects seen
      consecutively in an eye clinic were studied with a high-resolution optimal
      coherence tomography (OCT) pachymetry device and ophthalmic optical biometer. The
      relationships between corneal power, white-to-white (WTW) corneal diameter,
      anterior chamber diameter, and axial length were assessed with Pearson
      correlations. RESULTS: The mean age of the 61 subjects was 48.7 +/- 19.4 years.
      Corneal power was negatively correlated with axial length (r = -0.303, P < 0.01);
      WTW corneal diameter (r = -0.399, P < 0.001); and most interestingly, anterior
      chamber diameter (r = -0.646, P < 0.001). There was also a positive correlation
      between anterior chamber diameter and axial length (r = 0.489, P < 0.001).
      CONCLUSIONS: Greater anterior chamber diameters were associated with flatter
      corneas and, conversely, smaller anterior chamber diameters with steeper corneas.
      The growth patterns of the anterior segment may be determinants of corneal power.

PMID- 22589445
TI  - The dark atrophy with indocyanine green angiography in Stargardt disease.
AB  - PURPOSE: To evaluate differences in fluorescein angiography (FA) and indocyanine
      green angiography (ICGA), findings between subjects affected by Stargardt disease
      (STGD) and atrophic AMD. METHODS: This was a consecutive, cross-sectional case
      series. A total of 24 eyes of 12 patients with STGD and 23 eyes of 14 patients
      with atrophic AMD were enrolled in the study. Patients underwent dynamic
      simultaneous FA and ICGA using a dual beam confocal scanning system. Images were
      recorded from the initial filling of choroidal and retinal vessels throughout all
      the phases of the angiogram. Spectral-domain optical coherence tomography (SD
      OCT) and fundus autofluorescence were also executed. FA and ICGA findings in the
      two groups were evaluated. RESULTS: In 92% (22/24) of eyes affected by STGD, ICGA
      showed hypocyanescence from the areas of atrophy, more evident in the late
      phases. This finding, defined as ICGA-imaged "dark atrophy," was present in only
      13% (3/23) of the eyes affected by atrophic AMD. The remaining eyes in both
      groups showed iso- or mild hypercyanescence from the areas of atrophy. Eyes with
      ICGA-imaged dark atrophy, both in STGD and in atrophic AMD groups, did not show
      early obscuration of the choroidal vessels by FA. SD-OCT revealed morphologically
      intact choroid in STGD patients with ICGA-imaged dark atrophy. In atrophic AMD
      eyes with ICGA-imaged dark atrophy, SD-OCT revealed a severely thinned choroid.
      CONCLUSIONS: Hypocyanescence by ICGA from the areas of atrophy was more frequent
      in STGD compared with atrophic AMD. This finding, along with SD-OCT evidence of
      intact choroid, suggests a possible selective damage of the choriocapillaris in
      STGD.

PMID- 22589443
TI  - Effects of palmitoylethanolamide on aqueous humor outflow.
AB  - PURPOSE: To study the effects of palmitoylethanolamide (PEA), a fatty acid
      ethanolamide, on aqueous humor outflow facility. METHODS: The effects of PEA on
      outflow facility were measured using a porcine anterior segment-perfused organ
      culture model. The involvements of different receptors in PEA-induced changes
      were investigated using receptor antagonists and adenovirus delivered small
      hairpin RNAs (shRNAs). PEA-induced activation of p42/44 mitogen-activated protein
      kinase (MAPK) was determined by Western blot analysis using an antiphospho p42/44
      MAPK antibody. RESULTS: PEA caused a concentration-dependent enhancement of
      outflow facility, with the maximum effect (151.08 +/- 11.12% of basal outflow
      facility) achieved at 30 nM of PEA. Pretreatment of anterior segments with 1 MUM
      cannabinoid receptor 2 antagonist SR144528 and 1 MUM PPARalpha antagonist GW6471,
      but not 1 MUM cannabinoid receptor 1 antagonist SR141716A, produced a partial
      antagonism on the PEA-induced increase of outflow facility. Treatment of TM cells
      with PEA for 10 minutes activated phosphorylation of p42/44 MAPK, which was
      blocked by pretreatment with SR1444528 and GW6471, but not SR141716A. Knocking
      down the expression of either GPR55 or PPARalpha receptors with specific shRNAs
      for these receptors partially blocked PEA-induced increase in outflow facility
      and abolished PEA-induced phosphorylation of p42/44 MAPK. PD98059, an inhibitor
      of the p42/44 MAPK pathway, blocked both PEA-induced enhancement of aqueous humor
      outflow facility and PEA-induced phosphorylation of p42/44 MAPK. CONCLUSIONS: Our
      results demonstrate that PEA increases aqueous humor outflow through the TM
      pathway and these effects are mediated by GPR55 and PPARalpha receptors through
      activation of p42/44 MAPK.

PMID- 22589446
TI  - Quantification of retinal neural loss in patients with neuromyelitis optica and
      multiple sclerosis with or without optic neuritis using Fourier-domain optical
      coherence tomography.
AB  - PURPOSE: We compared retinal nerve fiber layer (RNFL) and macular thickness
      measurements in patients with multiple sclerosis (MS) and neuromyelitis optica
      (NMO) with or without a history of optic neuritis, and in controls using Fourier
      domain (FD) optical coherence tomography (OCT). METHODS: Patients with MS (n =
      60), NMO (n = 33), longitudinal extensive transverse myelitis (LETM, n = 28) and
      healthy controls (n = 41) underwent ophthalmic examination, including automated
      perimetry, and FD-OCT RNFL and macular thickness measurements. Five groups of
      eyes were compared: MS with or without previous optic neuritis, NMO, LETM, and
      controls. Correlation between OCT and visual field (VF) findings was
      investigated. RESULTS: With regard to most parameters, RNFL and macular thickness
      measurements were significantly smaller in eyes of each group of patients
      compared to controls. MS eyes with optic neuritis did not differ significantly
      from MS eyes without optic neuritis, but measurements were smaller in NMO eyes
      than in all other groups. RNFL (but not macular thickness) measurements were
      significantly smaller in LETM eyes than in controls. While OCT abnormalities were
      correlated significantly with VF loss in NMO/LETM and MS, the correlation was
      much stronger in the former. CONCLUSIONS: Although FD-OCT RNFL and macular
      thickness measurements can reveal subclinical or optic neuritis-related
      abnormalities in NMO-spectrum and MS patients, abnormalities are predominant in
      the macula of MS patients and in RFNL measurements in NMO patients. The
      correlation between OCT and VF abnormalities was stronger in NMO than in MS,
      suggesting the two conditions differ regarding structural and functional damage.
      (ClinicalTrials.gov number, NCT01024985.).

PMID- 22589447
TI  - Predictive value of retrobulbar blood flow velocities in glaucoma suspects.
AB  - PURPOSE: To determine whether retrobulbar blood flow (RBF) velocities are
      predictive of conversion to glaucoma. METHODS: A total of 262 glaucoma suspects
      were prospectively selected. Participants had normal visual field, increased
      intraocular pressure, and glaucomatous optic disc appearance at baseline.
      Topographic analysis of the optic nerve head was performed using a confocal laser
      scanning ophthalmoscope and the blood flow velocity of retrobulbar vessels was
      measured by color Doppler imaging. Conversion to glaucoma was assessed according
      to the changes in the color-coded Moorfields Regression Analysis (MRA)
      classification of the confocal laser scanning system during a 48-month follow-up
      period. Survival curves and hazard ratios (HRs) for the association between RBF
      parameters and conversion to glaucoma were calculated. RESULTS: End-diastolic
      velocity and mean velocity in the ophthalmic artery were reduced in subjects that
      converted to glaucoma based on MRA (36 individuals, 13.7%), while resistivity
      (RI) and pulsatility indices were increased in the same vessel. Patients with RI
      values lower than 0.75 in the ophthalmic artery had a survival rate (MRA
      converters versus nonconverters) of 93.9%, whereas individuals with RI values
      greater than 0.75 had a survival rate of 81.7% (HR = 3.306; P = 0.002).
      CONCLUSIONS: Abnormal RBF velocities measured by color Doppler ultrasound may be
      a risk factor for conversion to glaucoma. An RI value higher than 0.75 in the
      ophthalmic artery was associated with the development of glaucoma.

PMID- 22589449
TI  - Antithrombotic medication and incident open-angle glaucoma.
AB  - PURPOSE: To determine the associations between the use of antithrombotic drugs
      and incident open-angle glaucoma (OAG). METHODS: Ophthalmic examinations
      including measurements of the IOP and perimetry were performed at baseline and
      follow-up in 3939 participants of the prospective population-based Rotterdam
      Study who did not have OAG at baseline. The use of antithrombotic drugs was
      monitored continuously during follow-up. Antithrombotic drugs were stratified
      into anticoagulants and platelet aggregation inhibitors. Associations between
      incident OAG and the use of antithrombotic drugs were assessed using Cox
      regression; the model was adjusted for age, sex, baseline IOP and IOP-lowering
      treatment, family history of glaucoma, and myopia. Associations between
      antithrombotic drugs and IOP at follow-up were analyzed with multiple linear
      regression. RESULTS: During a mean follow-up of 9.8 years, 108 participants
      (2.7%) developed OAG. The hazard ratio for anticoagulant use was 0.90 (95%
      confidence interval [CI], 0.55-1.48; P = 0.69) and for platelet aggregation
      inhibitors 0.80 (0.53-1.21; P = 0.28). There was no trend towards a reduced or
      increased risk of incident OAG with prolonged anticoagulant use (P value for
      trend 0.84) or platelet aggregation inhibitor use (0.59). There was a significant
      IOP-lowering effect of anticoagulants (-0.31 mm Hg; 95% CI, -0.58 to -0.04 mm Hg;
      P = 0.025) but not of platelet aggregation inhibitors (P = 0.06). The IOP
      lowering effect of anticoagulants disappeared after additional adjustment for the
      use of systemic beta-blockers. CONCLUSIONS: Use of anticoagulants or platelet
      aggregation inhibitors appears not to be associated with incident OAG.

PMID- 22589448
TI  - Immunopathologic processes in sympathetic ophthalmia as signified by microRNA
      profiling.
AB  - PURPOSE: Recent discovery of microRNAs and their negative gene regulation have
      provided new understanding in the pathogenesis of inflammatory diseases. This
      study demonstrated microRNA expression profiling and their likely role in
      sympathetic ophthalmia, using formalin-fixed, paraffin embedded samples. METHODS:
      Two groups of four enucleated globes (total eight globes) from patients with
      clinical and histopathological diagnosis of SO (experimental samples) and one
      group of four age-matched, noninflamed enucleated globes (control samples) were
      used. Human genome-wide microRNA PCR array was performed and results were
      subjected to bioinformatics calculation and P values stringency tests. The
      targets were searched using the recently published and periodically updated
      miRWalk software. Quantitative real-time PCR and immunohistochemical staining
      were performed to confirm the validated targets in the mRNA and in the protein
      levels, respectively. RESULTS: No microRNA was significantly upregulated in SO,
      but 27 microRNAs were significantly downregulated. Among these, four microRNAs
      (hsa-miR-1, hsa-let-7e, hsa-miR-9, and hsa-miR-182) were known to be associated
      with the inflammatory signaling pathway. Only hsa-miR-9 has the validated
      targets, tumor necrosis factor-alpha, and nuclear factor kappa B1, which have
      been previously shown to be associated with mitochondrial oxidative stress
      mediated photoreceptor apoptosis in eyes with SO. CONCLUSIONS: Identification of
      altered levels of microRNAs by microRNA expression profiling may yield new
      insights into the pathogenesis of SO by disclosing specific microRNA signatures.
      In the future these may be targeted by synthetic microRNA mimic-based therapeutic
      strategies.

PMID- 22589450
TI  - Gastroenteropancreatic neuroendocrine tumors: update on therapeutics.
AB  - OBJECTIVE: To review the available literature addressing the treatment of
      pancreatic neuroendocrine tumors (PNETs) and carcinoid tumors. DATA SOURCES:
      Relevant literature was identified by a PubMed search (January 1977-December
      2011) of English-language literature using the terms gastroenteropancreatic
      neuroendocrine tumor, pancreatic neuroendocrine, carcinoid, and pancreatic islet
      cell tumor. STUDY SELECTION AND DATA EXTRACTION: All published studies and
      abstracts, as well as relevant consensus guidelines, evaluating the current
      literature about PNETs and carcinoid tumors were included. DATA SYNTHESIS:
      Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a genetically diverse
      group of complex malignancies with varying biological and clinical courses.
      Historically believed to be rare, recent epidemiologic data suggest their
      incidence is rising. Two of the most commonly diagnosed GEP-NETs are PNETs and
      carcinoid tumors. Both subtypes are well-differentiated tumors and present as low
      or intermediate grade. The systemic manifestations of PNETs and carcinoid tumors
      are diverse and are related to the secretion of affected hormones and biogenic
      amines. Surgical resection of localized disease remains the only curative option.
      However, the utility of this approach is limited because most patients are
      diagnosed with advanced disease. Recent advances have led to an improvement in
      outcomes in patients with PNETs and carcinoid tumors. This review describes
      traditional therapies as well as emerging strategies being investigated to help
      manage these cancers. Treatment of poorly differentiated GEP-NETs is beyond the
      scope of this review. CONCLUSIONS: The advent of new therapies for PNETs and
      carcinoid tumors has introduced a paradigm shift in the management of this
      heterogeneous malignancy.

PMID- 22589451
TI  - Tocilizumab for the treatment of juvenile idiopathic arthritis.
AB  - OBJECTIVE: To evaluate the pharmacology, clinical efficacy, safety, and role of
      tocilizumab for the treatment of juvenile idiopathic arthritis. DATA SOURCES: A
      literature search via MEDLINE through PubMed (1970-December 2011) and
      International Pharmaceutical Abstracts (1970-December 2011) was performed to
      identify clinical trials and review articles. The key search terms tocilizumab,
      anti-interleukin 6, and juvenile idiopathic arthritis were used, with several
      combinations of terms. Bibliographies of selected articles were examined to
      identify additional references, and ongoing trials were identified through a
      review of www.clinicaltrials.gov. STUDY SELECTION AND DATA EXTRACTION: Articles
      were limited to those published in English and studies in humans. Studies
      included in the review examined pediatric data in systemic and polyarticular
      juvenile idiopathic arthritis. Background information was obtained through
      reviews of literature on a wide variety of autoimmune disease states in both
      adult and pediatric populations. DATA SYNTHESIS: Tocilizumab is Food and Drug
      Administration-approved for use in patients aged 2 years and older with systemic
      juvenile idiopathic arthritis. Tocilizumab was superior to placebo in triggering
      a symptomatic response during Phase 2 and 3 clinical trials. Tocilizumab was
      determined to be safe, with only a small number of serious adverse drug events
      occurring within studies. CONCLUSIONS: Tocilizumab provides expansion of the
      available options for the treatment of systemic juvenile idiopathic arthritis,
      specifically in patients who have not responded to conventional therapies.
      Tocilizumab is relatively well tolerated and has proven efficacy for up to 52
      weeks. Further studies are warranted to determine its utility as a first-line
      option for systemic juvenile idiopathic arthritis as well as its role within the
      treatment of polyarticular juvenile idiopathic arthritis.

PMID- 22589452
TI  - Social anxiety mediates the effect of autism spectrum disorder characteristics on
      hostility in young adults.
AB  - Problems with social anxiety are frequently reported in people with autism
      spectrum disorders (ASD). It is possible that social anxiety, when present,
      exacerbates the experience of hostility and other forms of aggression in relation
      to ASD symptoms. This study sought to determine if social anxiety symptoms
      mediate the relationship between features of ASD and feelings of hostility in
      young adults. Self-report measures of social anxiety, ASD, and facets of
      aggression were collected in a non-clinical sample (n = 618) of college students.
      Social anxiety was found to partially mediate the relationship between ASD
      features and self-reported hostility. There was also evidence for inconsistent
      mediation, such that social anxiety dampened the strength of the relationship
      between ASD symptoms and verbal and physical aggression. Findings highlight the
      potential influence of associated psychiatric symptoms in people with ASD. In
      addition, dimensional conceptualization of ASD symptoms, as opposed to a
      categorical approach solely, may be a useful approach to studying complex
      personality processes.

PMID- 22589453
TI  - Prevalence of autism spectrum disorder symptomatology and related behavioural
      characteristics in individuals with Down syndrome.
AB  - We evaluated the proportion of individuals with Down syndrome (DS: N = 108) who
      met criteria for autism spectrum disorder (ASD) on the Social Communication
      Questionnaire and the severity of ASD-related symptomatology in this group. The
      proportions of individuals with DS meeting the cut-off for ASD and autism in this
      sample were 19% and 8%, respectively. We then evaluated the behavioural profile
      of individuals with DS who scored above cut-off for ASD (DS+ASD; N = 17) compared
      with those with DS-only (N = 17) and individuals with idiopathic ASD (N = 17),
      matched for adaptive behaviour skills and ASD symptom severity (ASD group only).
      Individuals in the DS+ASD and ASD-only groups showed more stereotyped behaviour,
      repetitive language, overactivity and self-injury than the DS-only group (p <
      .001). Individuals in the DS+ASD and DS-only groups appeared less withdrawn from
      their surroundings than those with ASD (p < .004). These findings indicate
      differences in the behavioural and cognitive profile of individuals with DS+ASD
      compared with those with DS-only, when controlling for adaptive behaviour skills.
      Individuals with DS+ASD show broad similarities with individuals with idiopathic
      ASD with regard to ASD and behavioural characteristics but may also show some
      areas of subtle difference from this group. 

PMID- 22589455
TI  - High frequency of vitamin D deficiency in HIV-infected patients: effects of HIV
      related factors and antiretroviral drugs.
AB  - OBJECTIVES: The aim of this study was to assess 25-hydroxyvitamin D (vitamin D)
      status in an HIV-infected adult population and to define HIV- and antiretroviral
      related factors associated with vitamin D deficiency. METHODS: Using data from a
      prospective cohort of HIV-infected adult patients followed in five French centres
      (Dat'AIDS cohort), we evaluated the prevalence of vitamin D
      deficiency/insufficiency (<30 ng/mL). A multiple linear regression model was used
      to examine risk factors for vitamin D deficiency (<=10 ng/mL). RESULTS: Vitamin D
      deficiency/insufficiency was observed in 86.7% of the 2994 patients, including
      55.6% with vitamin D insufficiency and 31.1% with vitamin D deficiency. In
      multivariate analysis, factors associated with vitamin D deficiency were current
      smoking [adjusted OR (aOR) 1.55], estimated glomerular filtration rate >=90
      mL/min/1.73 m(2) (aOR 1.51), vitamin D measurement not performed in summer (aOR
      0.27), CD4 <350 cells/mm(3) (aOR 1.37 for CD4 200 to <350 and 1.62 for CD4 <200
      cells/mm(3)) and antiretroviral therapy (aOR 2.61). Gender, body mass index, age,
      coinfection and previous AIDS were not associated factors. In the antiretroviral
      treated population (n = 2660), besides the same factors found in the whole
      population, efavirenz was the only drug to be significantly associated with
      deficiency, with an aOR of 1.89 (95% CI 1.45-2.47). CONCLUSIONS: Vitamin D
      deficiency is frequent in this HIV-infected population. Patients on
      antiretroviral therapy are at higher risk of vitamin D deficiency than
      antiretroviral-naive patients, with an increased risk in patients receiving
      efavirenz. No effect of the other antiretrovirals, including the latest
      (etravirine, darunavir, raltegravir), was found.

PMID- 22589454
TI  - Genetic locus on mouse chromosome 7 controls elevated heart rate.
AB  - Elevated heart rate (HR) is a risk factor for cardiovascular diseases. The goal
      of the study was to map HR trait in mice using quantitative trait locus (QTL)
      analysis followed by genome-wide association (GWA) analysis. The first approach
      provides mapping power and the second increases genome resolution. QTL analyses
      were performed in a C3HeB*SJL backcross. HR and systolic blood pressure (SBP)
      were measured by the tail-cuff plethysmography. HR was ~80 beats/min higher in
      SJL compared with C3HeB. There was a wide distribution of the HR (536-763
      beats/min) in N2 mice. We discovered a highly significant QTL (logarithm of odds
      = 6.7, P < 0.001) on chromosome 7 (41 cM) for HR in the C3HeB*SJL backcross. In
      the Hybrid Mouse Diversity Panel (58 strains, n = 5-6/strain) we found that HR
      (beats/min) ranged from 546 +/- 12 in C58/J to 717 +/- 7 in MA/MyJ mice. SBP
      (mmHg) ranged from 99 +/- 6 in strain I/LnJ to 151 +/- 4 in strain BXA4/PgnJ. GWA
      analyses were done using the HMDP, which revealed a locus (64.2-65.1 Mb) on
      chromosome 7 that colocalized with the QTL for elevated HR found in the C3HeB*SJL
      backcross. The peak association was observed for 17 SNPs that are localized
      within three GABA(A) receptor genes. In summary, we used a combined genetic
      approach to fine map a novel elevated HR locus on mouse chromosome 7.

PMID- 22589458
TI  - Withholding anticoagulation following a single negative whole-leg ultrasound in
      patients at high pretest probability for deep vein thrombosis.
AB  - Prompt, accurate diagnosis of deep vein thrombosis (DVT) is essential. A single,
      whole-leg ultrasound (whole-leg US) has been used to exclude DVT, but limited
      data exist for patients with high pretest probability (PTP) for DVT. This
      diagnostic management study tested the rate of venous thromboembolism (VTE) in
      patients with a PTP of "DVT likely" per the simplified Wells score when
      anticoagulation is withheld based on a single, negative whole-leg US. Consecutive
      patients presenting during coordinator shifts with a PTP of DVT likely were
      enrolled. Anticoagulation was withheld after a single, negative whole-leg US. The
      outcome was objectively confirmed VTE in 3 months. All 167 patients completed the
      follow-up. A single patient death was adjudicated as possibly caused by VTE,
      resulting in a VTE rate of 0.60% (95% confidence interval: 0.02%-3.29%). Whole
      leg US should be further studied in diagnostic algorithms that utilize PTP
      scoring and D-dimer testing.

PMID- 22589456
TI  - Glycyrrhizic acid suppresses Cox-2-mediated anti-inflammatory responses during
      Leishmania donovani infection.
AB  - OBJECTIVES: The aim of the present study was to characterize glycyrrhizic acid
      (GA) and assess its immunomodulatory potential in a model of experimental
      visceral leishmaniasis. METHODS: The antileishmanial activity of GA was tested in
      an amastigote-macrophage model and its non-cytotoxic dose was measured by a cell
      viability assay. To understand the effector mechanism of GA-treated macrophages
      against leishmanial parasites, real-time PCR analysis of inducible nitric oxide
      synthase 2 (iNOS2) was carried out followed by measurement of nitric oxide
      generation by Griess reagent. The effect of GA on the production of cytokines,
      such as interleukin (IL)-12, tumour necrosis factor (TNF)-alpha, IL-10 and
      transforming growth factor (TGF)-beta, was measured by ELISA (protein) and real
      time PCR. The expression of iNOS2 and cyclooxygenase-2 (Cox-2) was studied by
      western blotting. The parasite burden of the liver and spleen following GA
      treatment was determined by the stamp-smear method, and T cell proliferation was
      assessed via [3H]thymidine uptake, measured by a liquid scintillation counter.
      RESULTS: Results showed that GA treatment caused an enhanced expression of iNOS2
      along with inhibition of Cox-2 in Leishmania donovani-infected macrophages. GA
      treatment in infected macrophages enhanced the expression of IL-12 and TNF-alpha,
      concomitant with a down-regulation of IL-10 and TGF-beta. GA increased macrophage
      effector responses via inhibition of Cox-2-mediated prostaglandin E2 release in
      L. donovani-infected macrophages. GA also decreased hepatic and splenic parasite
      burden and increased T cell proliferation in Leishmania-infected BALB/c mice.
      CONCLUSIONS: These results provide a mechanistic understanding of GA-mediated
      protection against leishmanial parasites within the host.

PMID- 22589459
TI  - A study of thrombophilia testing and counseling practices of family physicians
      using the script concordance method in Calgary, Canada.
AB  - BACKGROUND: Thrombophilia testing helps to identify populations at risk of venous
      thromboembolism, but motivations for testing individuals are frequently unclear.
      OBJECTIVES: Our goals were to assess the motivations for thrombophilia testing
      among family physicians (FPs) to determine whether testing was congruent with
      expert opinion, and to study counseling practices. METHODS: The FPs and experts
      completed a survey involving hypothetical thrombophilia patients. Responses
      between groups were compared using the script concordance method. RESULTS: The
      FPs referred 35.9% of cases. Of the five scenarios, two resulted in disagreement
      regarding appropriateness of testing (P <= .037). The FPs were more likely to
      test male, obese, or pediatric patients, patients with a family history of
      myocardial infarction or infertility, and patients with a recent event (P <=
      .043). The FPs were more likely to counsel patients after testing (P <= .016).
      CONCLUSION: Disagreement exists between physician groups about the utility of
      thrombophilia testing. Self-reported lack of pretest counseling among FPs
      warrants further study.

PMID- 22589460
TI  - Determination of factor V Leiden mutation and R2 polymorphism in cis position.
AB  - FVA4070G (R2 polymorphism) influences plasma factor V (FV) concentration and was
      associated with mild activated protein C resistance. This polymorphism was
      reported to have a trans inheritance with FV Leiden (FVL) mutation. The aim of
      this study is to investigate the inheritance of R2 polymorphism in the homozygous
      FVL carriers. In this study, 99 patients with thrombosis and 7 individuals
      without a history of thrombosis all of which homozygous for FVL were included. Of
      99 patients, 1 was heterozygous for FV A4070G. Additionally, 6 polymorphisms in
      the FV gene were analyzed for the heterozygous R2 patient and her family. When
      the allelic distribution was classified, 8 different haplotypes were obtained. In
      contrast to the literature, it was shown that R2 polymorphism could be inherited
      in cis position with FVL and also the family members could have co-inheritance of
      the FVL and R2 on the same chromosome as proband. 

PMID- 22589461
TI  - Effects of an enjoyable nurse-led intervention to promote movement in poststroke
      inpatients.
AB  - It is important to have the stroke survivors move as soon as possible to improve
      disability as well as related problems such as fatigue, sleep, and depression.
      However, there were few reports on a movement intervention for the inpatients who
      were in the rehabilitation unit just after taking acute care. An enjoyable
      intervention was developed that promoted movement focusing on plegic limbs and
      looked more like a game or a play; the game was designed to be a group activity
      that could be led by nurses. Twenty participants participated in 30- to 40-min
      sessions, 3 times a week for 2 weeks. Functional status (cognitive, motor, and
      total), fatigue, sleep, and depression were measured. Except for the cognitive
      function, all outcomes were significantly improved in the experimental group as
      compared to those in the control group. Safe and enjoyable nursing interventions
      should be developed and implemented to improve disability and related problems
      for the poststroke inpatients.

PMID- 22589462
TI  - Sex knowledge in males and females recovering from a myocardial infarction: a
      brief communication.
AB  - The purpose of this article was to explore sexual knowledge in persons who had
      suffered from myocardial infarction (MI). Seventy-six Swedish persons completed
      the "Sex after MI Knowledge Test" questionnaire. Overall, 53% of the men and 45%
      of the women scored maximum in the test. In a comparison between sexes, the men
      scored significantly more often a correct answer compared to the women for two
      out of the 25 items. The levels of correct answers were less then 50% for 14 out
      of the 25 items in both sexes. In conclusion we found that people who had
      suffered MI had poor levels of knowledge about sex and that there were some
      differences concerning lesser knowledge among the females in comparison to males.
      In regard to application, using a validated instrument facilitates an interactive
      communication between the patient and health care professionals, and opens up for
      a tailored education in line with the patient's and his or her partner's needs.

PMID- 22589463
TI  - A membrane microdomain-associated protein, Arabidopsis Flot1, is involved in a
      clathrin-independent endocytic pathway and is required for seedling development.
AB  - Endocytosis is essential for the maintenance of protein and lipid compositions in
      the plasma membrane and for the acquisition of materials from the extracellular
      space. Clathrin-dependent and -independent endocytic processes are well
      established in yeast and animals; however, endocytic pathways involved in cargo
      internalization and intracellular trafficking remain to be fully elucidated for
      plants. Here, we used transgenic green fluorescent protein-flotillin1 (GFP-Flot1)
      Arabidopsis thaliana plants in combination with confocal microscopy analysis and
      transmission electron microscopy immunogold labeling to study the spatial and
      dynamic aspects of GFP-Flot1-positive vesicle formation. Vesicle size, as
      outlined by the gold particles, was ~100 nm, which is larger than the 30-nm size
      of clathrin-coated vesicles. GFP-Flot1 also did not colocalize with clathrin
      light chain-mOrange. Variable-angle total internal reflection fluorescence
      microscopy also revealed that the dynamic behavior of GFP-Flot1-positive puncta
      was different from that of clathrin light chain-mOrange puncta. Furthermore,
      disruption of membrane microdomains caused a significant alteration in the
      dynamics of Flot1-positive puncta. Analysis of artificial microRNA Flot1
      transgenic Arabidopsis lines established that a reduction in Flot1 transcript
      levels gave rise to a reduction in shoot and root meristem size plus retardation
      in seedling growth. Taken together, these findings support the hypothesis that,
      in plant cells, Flot1 is involved in a clathrin-independent endocytic pathway and
      functions in seedling development.

PMID- 22589464
TI  - Grass microRNA gene paleohistory unveils new insights into gene dosage balance in
      subgenome partitioning after whole-genome duplication.
AB  - The recent availability of plant genome sequences, combined with a robust
      evolutionary scenario of the modern monocot and eudicot karyotypes from their
      diploid ancestors, offers an opportunity to gain insights into microRNA (miRNA)
      gene paleohistory in plants. Characterization and comparison of miRNAs and
      associated protein-coding targets in plants allowed us to unravel (1) contrasted
      genome conservation patterns of miRNAs in monocots and eudicots after whole
      genome duplication (WGD), (2) an ancestral miRNA founder pool in the monocot
      genomes dating back to 100 million years ago, (3) miRNA subgenome dominance
      during the post-WGD diploidization process with selective miRNA deletion
      complemented with possible transposable element-mediated return flows, and (4)
      the miRNA/target interaction-directed differential loss/retention of miRNAs
      following the gene dosage balance rule. Together, our data suggest that
      overretained miRNAs in grass genomes may be implicated in connected gene
      regulations for stress responses, which is essential for plant adaptation and
      useful for crop variety innovation.

PMID- 22589465
TI  - Cytosolic glyceraldehyde-3-phosphate dehydrogenases interact with phospholipase
      Ddelta to transduce hydrogen peroxide signals in the Arabidopsis response to
      stress.
AB  - Reactive oxygen species (ROS) are produced in plants under various stress
      conditions and serve as important mediators in plant responses to stresses. Here,
      we show that the cytosolic glycolytic enzymes glyceraldehyde-3-phosphate
      dehydrogenases (GAPCs) interact with the plasma membrane-associated phospholipase
      D (PLDdelta) to transduce the ROS hydrogen peroxide (H(2)O(2)) signal in
      Arabidopsis thaliana. Genetic ablation of PLDdelta impeded stomatal response to
      abscisic acid (ABA) and H(2)O(2), placing PLDdelta downstream of H(2)O(2) in
      mediating ABA-induced stomatal closure. To determine the molecular link between
      H(2)O(2) and PLDdelta, GAPC1 and GAPC2 were identified to bind to PLDdelta, and
      the interaction was demonstrated by coprecipitation using proteins expressed in
      Escherichia coli and yeast, surface plasmon resonance, and bimolecular
      fluorescence complementation. H(2)O(2) promoted the GAPC-PLDdelta interaction and
      PLDdelta activity. Knockout of GAPCs decreased ABA- and H(2)O(2)-induced
      activation of PLD and stomatal sensitivity to ABA. The loss of GAPCs or PLDdelta
      rendered plants less responsive to water deficits than the wild type. The results
      indicate that the H(2)O(2)-promoted interaction of GAPC and PLDdelta may provide
      a direct connection between membrane lipid-based signaling, energy metabolism and
      growth control in the plant response to ROS and water stress.

PMID- 22589467
TI  - Nramp5 is a major transporter responsible for manganese and cadmium uptake in
      rice.
AB  - Paddy rice (Oryza sativa) is able to accumulate high concentrations of Mn without
      showing toxicity; however, the molecular mechanisms underlying Mn uptake are
      unknown. Here, we report that a member of the Nramp (for the Natural Resistance
      Associated Macrophage Protein) family, Nramp5, is involved in Mn uptake and
      subsequently the accumulation of high concentrations of Mn in rice. Nramp5 was
      constitutively expressed in the roots and encodes a plasma membrane-localized
      protein. Nramp5 was polarly localized at the distal side of both exodermis and
      endodermis cells. Knockout of Nramp5 resulted in a significant reduction in
      growth and grain yield, especially when grown at low Mn concentrations. This
      growth reduction could be partially rescued by supplying high concentrations of
      Mn but not by the addition of Fe. Mineral analysis showed that the concentration
      of Mn and Cd in both the roots and shoots was lower in the knockout line than in
      wild-type rice. A short-term uptake experiment revealed that the knockout line
      lost the ability to take up Mn and Cd. Taken together, Nramp5 is a major
      transporter of Mn and Cd and is responsible for the transport of Mn and Cd from
      the external solution to root cells.

PMID- 22589466
TI  - The recombinases DMC1 and RAD51 are functionally and spatially separated during
      meiosis in Arabidopsis.
AB  - Meiosis ensures the reduction of the genome before the formation of generative
      cells and promotes the exchange of genetic information between homologous
      chromosomes by recombination. Essential for these events are programmed DNA
      double strand breaks (DSBs) providing single-stranded DNA overhangs after their
      processing. These overhangs, together with the RADiation sensitive51 (RAD51) and
      DMC1 Disrupted Meiotic cDNA1 (DMC1) recombinases, mediate the search for
      homologous sequences. Current models propose that the two ends flanking a meiotic
      DSB have different fates during DNA repair, but the molecular details remained
      elusive. Here we present evidence, obtained in the model plant Arabidopsis
      thaliana, that the two recombinases, RAD51 and DMC1, localize to opposite sides
      of a meiotic DSB. We further demonstrate that the ATR kinase is involved in
      regulating DMC1 deposition at meiotic DSB sites, and that its elimination allows
      DMC1-mediated meiotic DSB repair even in the absence of RAD51. DMC1's ability to
      promote interhomolog DSB repair is not a property of the protein itself but the
      consequence of an ASYNAPTIC1 (Hop1)-mediated impediment for intersister repair.
      Taken together, these results demonstrate that DMC1 functions independently and
      spatially separated from RAD51 during meiosis and that ATR is an integral part of
      the regular meiotic program.

PMID- 22589468
TI  - Plant vegetative and animal cytoplasmic actins share functional competence for
      spatial development with protists.
AB  - Actin is an essential multifunctional protein encoded by two distinct ancient
      classes of genes in animals (cytoplasmic and muscle) and plants (vegetative and
      reproductive). The prevailing view is that each class of actin variants is
      functionally distinct. However, we propose that the vegetative plant and
      cytoplasmic animal variants have conserved functional competence for spatial
      development inherited from an ancestral protist actin sequence. To test this
      idea, we ectopically expressed animal and protist actins in Arabidopsis thaliana
      double vegetative actin mutants that are dramatically altered in cell and organ
      morphologies. We found that expression of cytoplasmic actins from humans and even
      a highly divergent invertebrate Ciona intestinalis qualitatively and
      quantitatively suppressed the root cell polarity and organ defects of act8 act7
      mutants and moderately suppressed the root-hairless phenotype of act2 act8
      mutants. By contrast, human muscle actins were unable to support prominently any
      aspect of plant development. Furthermore, actins from three protists representing
      Choanozoa, Archamoeba, and green algae efficiently suppressed all the phenotypes
      of both the plant mutants. Remarkably, these data imply that actin's competence
      to carry out a complex suite of processes essential for multicellular development
      was already fully developed in single-celled protists and evolved
      nonprogressively from protists to plants and animals.

PMID- 22589469
TI  - Systematic identification of functional plant modules through the integration of
      complementary data sources.
AB  - A major challenge is to unravel how genes interact and are regulated to exert
      specific biological functions. The integration of genome-wide functional genomics
      data, followed by the construction of gene networks, provides a powerful approach
      to identify functional gene modules. Large-scale expression data, functional gene
      annotations, experimental protein-protein interactions, and transcription factor
      target interactions were integrated to delineate modules in Arabidopsis
      (Arabidopsis thaliana). The different experimental input data sets showed little
      overlap, demonstrating the advantage of combining multiple data types to study
      gene function and regulation. In the set of 1,563 modules covering 13,142 genes,
      most modules displayed strong coexpression, but functional and cis-regulatory
      coherence was less prevalent. Highly connected hub genes showed a significant
      enrichment toward embryo lethality and evidence for cross talk between different
      biological processes. Comparative analysis revealed that 58% of the modules
      showed conserved coexpression across multiple plants. Using module-based
      functional predictions, 5,562 genes were annotated, and an evaluation experiment
      disclosed that, based on 197 recently experimentally characterized genes, 38.1%
      of these functions could be inferred through the module context. Examples of
      confirmed genes of unknown function related to cell wall biogenesis, xylem and
      phloem pattern formation, cell cycle, hormone stimulus, and circadian rhythm
      highlight the potential to identify new gene functions. The module-based
      predictions offer new biological hypotheses for functionally unknown genes in
      Arabidopsis (1,701 genes) and six other plant species (43,621 genes).
      Furthermore, the inferred modules provide new insights into the conservation of
      coexpression and coregulation as well as a starting point for comparative
      functional annotation.

PMID- 22589470
TI  - Agrobacterium tumefaciens tumor morphology root plastid localization and
      preferential usage of hydroxylated prenyl donor is important for efficient gall
      formation.
AB  - Upon Agrobacterium tumefaciens infection of a host plant, Tumor morphology root
      (Tmr) a bacterial adenosine phosphate-isopentenyltransferase (IPT), creates a
      metabolic bypass in the plastid for direct synthesis of trans-zeatin (tZ) with 1
      hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate as the prenyl donor. To understand
      the biological importance of Tmr function for gall formation, we compared Tmr and
      Trans-zeatin secretion (Tzs) another agrobacterial IPT that functions within the
      bacterial cell. Although there is no significant difference in their substrate
      specificities in vitro, ectopic overexpression of Tzs in Arabidopsis (Arabidopsis
      thaliana) resulted in the accumulation of comparable amounts of tZ- and N6
      (Delta2-isopentenyl)adenine (iP)-type cytokinins, whereas overexpression of Tmr
      resulted exclusively in the accumulation of tZ-type cytokinins. Ectopic
      expression of Tzs in plant cells yields only small amounts of the polypeptide in
      plastid-enriched fractions. Obligatory localization of Tzs into Arabidopsis
      plastid stroma by translational fusions with ferredoxin transit peptide (TP-Tzs)
      increased the accumulation of both tZ- and iP-type cytokinins. Replacement of tmr
      on the Ti plasmid with tzs, TP-tzs, or an Arabidopsis plastidic IPT induced the
      formation of smaller galls than wild-type A. tumefaciens, and they were
      accompanied by the accumulation of iP-type cytokinins. Tmr is thus specialized
      for plastid localization and preferential usage of 1-hydroxy-2-methyl-2-(E)
      butenyl 4-diphosphate in vivo and is important for efficient gall formation.

PMID- 22589471
TI  - Global health for future ophthalmologists--time to address the gaps: a UK
      perspective.

PMID- 22589472
TI  - Deferasirox reduces iron overload significantly in nontransfusion-dependent
      thalassemia: 1-year results from a prospective, randomized, double-blind, placebo
      controlled study.
AB  - Nontransfusion-dependent thalassemia (NTDT) patients may develop iron overload
      and its associated complications despite receiving only occasional or no
      transfusions. The present 1-year, randomized, double-blind, placebo-controlled
      THALASSA (Assessment of Exjade in Nontransfusion-Dependent Thalassemia) trial
      assessed the efficacy and safety of deferasirox in iron-overloaded NTDT patients.
      A total of 166 patients were randomized in a 2:1:2:1 ratio to starting doses of 5
      or 10 mg/kg/d of deferasirox or placebo. The means +/- SD of the actual
      deferasirox doses received over the duration of the study in the 5 and 10 mg/kg/d
      starting dose cohorts were 5.7 +/- 1.4 and 11.5 +/- 2.9 mg/kg/d, respectively. At
      1 year, the liver iron concentration (LIC) decreased significantly compared with
      placebo (least-squares mean [LSM] +/- SEM, -2.33 +/- 0.7 mg Fe/g dry weight [dw],
      P = .001, and -4.18 +/- 0.69 mg Fe/g dw, P < .001) for the 5 and 10 mg/kg/d
      deferasirox groups, respectively (baseline values [means +/- SD], 13.11 +/- 7.29
      and 14.56 +/- 7.92 mg Fe/g dw, respectively). Similarly, serum ferritin decreased
      significantly compared with placebo by LSM -235 and -337 ng/mL for the
      deferasirox 5 and 10 mg/kg/d groups, respectively (P < .001). In the placebo
      patients, LIC and serum ferritin increased from baseline by 0.38 mg Fe/g dw and
      115 ng/mL (LSM), respectively. The most common drug-related adverse events were
      nausea (n = 11; 6.6%), rash (n = 8; 4.8%), and diarrhea (n = 6; 3.6%). This is
      the first randomized study showing that iron chelation with deferasirox
      significantly reduces iron overload in NTDT patients with a frequency of overall
      adverse events similar to placebo.

PMID- 22589473
TI  - Transcytosis of HTLV-1 across a tight human epithelial barrier and infection of
      subepithelial dendritic cells.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T
      cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic
      paraparesis. In addition to blood transfusion and sexual transmission, HTLV-1 is
      transmitted mainly through prolonged breastfeeding, and such infection represents
      a major risk for the development of adult T-cell leukemia/lymphoma. Although HTLV
      1-infected lymphocytes can be retrieved from maternal milk, the mechanisms of
      HTLV-1 transmission through the digestive tract remain unknown. In the present
      study, we assessed HTLV-1 transport across the epithelial barrier using an in
      vitro model. Our results show that the integrity of the epithelial barrier was
      maintained during coculture with HTLV-1-infected lymphocytes, because neither
      morphological nor functional alterations of the cell monolayer were observed.
      Enterocytes were not susceptible to HTLV-1 infection, but free infectious HTLV-1
      virions could cross the epithelial barrier via a transcytosis mechanism. Such
      virions were able to infect productively human dendritic cells located beneath
      the epithelial barrier. Our data indicate that HTLV-1 crosses the tight
      epithelial barrier without disruption or infection of the epithelium to further
      infect target cells such as dendritic cells. The present study provides the first
      data pertaining to the mode of HTLV-1 transport across a tight epithelial
      barrier, as can occur during mother-to-child HTLV-1 transmission during
      breastfeeding.

PMID- 22589474
TI  - Granule exocytosis is required for platelet spreading: differential sorting of
      alpha-granules expressing VAMP-7.
AB  - There has been recent controversy as to whether platelet alpha-granules represent
      a single granule population or are composed of different subpopulations that
      serve discrete functions. To address this question, we evaluated the localization
      of vesicle-associated membrane proteins (VAMPs) in spread platelets to determine
      whether platelets actively sort a specific subpopulation of alpha-granules to the
      periphery during spreading. Immunofluorescence microscopy demonstrated that
      granules expressing VAMP-3 and VAMP-8 localized to the central granulomere of
      spread platelets along with the granule cargos von Willebrand factor and
      serotonin. In contrast, alpha-granules expressing VAMP-7 translocated to the
      periphery of spread platelets along with the granule cargos TIMP2 and VEFG. Time
      lapse microscopy demonstrated that alpha-granules expressing VAMP-7 actively
      moved from the granulomere to the periphery during spreading. Platelets from a
      patient with gray platelet syndrome lacked alpha-granules and demonstrated only
      minimal spreading. Similarly, spreading was impaired in platelets obtained from
      Unc13d(Jinx) mice, which are deficient in Munc13-4 and have an exocytosis defect.
      These studies identify a new alpha-granule subtype expressing VAMP-7 that moves
      to the periphery during spreading, supporting the premise that alpha-granules are
      heterogeneous and demonstrating that granule exocytosis is required for platelet
      spreading.

PMID- 22589475
TI  - Pediatricians' perceptions of an off-site collaboration with child psychiatry.

PMID- 22589476
TI  - In-office influenza vaccination by US pediatric providers varies greatly and is
      higher among smaller offices.
AB  - During the 2010-2011 US influenza season, 105 pediatric and 13 family practice
      offices participated in a prospective observational study of in-office influenza
      vaccination of children. Office characteristics, influenza vaccinations, and
      vaccination-related activities were reported. Among pediatric offices, first dose
      vaccination rates (2% to 60%), 2-dose compliance (11% to 100%), the duration of
      vaccine availability (60-302 days), and office visit type (well vs sick vs
      clinic) used for vaccinations varied greatly. Pediatric offices had higher
      vaccination coverage than family practice offices, offered vaccine longer, and
      administered more vaccinations during sick visits. Smaller offices and higher
      staff vaccination rates were associated with higher vaccination coverage. Smaller
      offices and video reminders in waiting rooms were associated with enhanced 2-dose
      compliance among children younger than 9 years. A greater understanding of
      interoffice variability in influenza vaccine delivery by US pediatric providers
      should allow for the creation of more effective strategies to improve pediatric
      influenza vaccination rates.

PMID- 22589478
TI  - Compliance of middle school-aged babysitters in central Pennsylvania with
      national recommendations for emergency preparedness and safety practices.
AB  - OBJECTIVE: To determine the compliance of middle school-aged babysitters with
      national recommendations for emergency preparedness and safety practices.
      PATIENTS AND METHODS: A prospective, self-administered questionnaire-based study
      was conducted at 3 middle schools in central Pennsylvania. RESULTS: A total of
      1364 questionnaires were available for analysis. Responding babysitters (n = 890)
      reported previous training that included babysitter (21%), first aid (64%), and
      cardiopulmonary resuscitation (59%) training. Reported unsafe babysitter
      practices were leaving a child unattended (36%) and opening the door to a
      stranger (24%). The most common emergency experience encountered by responding
      babysitters included cut or scrape (83%), burns (28%), and choking (14%). Ten
      percent of responding babysitters have activated the 911 system. CONCLUSIONS:
      Middle school-aged babysitters will likely encounter common household emergencies
      and therefore benefit from first aid training; however, very little difference in
      safety knowledge was found between trained and untrained babysitters, suggesting
      modifications in babysitter training programs may be required.

PMID- 22589477
TI  - Perspectives on decision making about human papillomavirus vaccination among 11-
      to 12-year-old girls and their mothers.
AB  - Introduction. The aims of this qualitative study were to explore (a) the factors
      influencing mothers' decisions to vaccinate 11- to 12-year-old daughters against
      human papillomavirus (HPV) and (b) the mothers' and daughters' perspectives about
      HPV vaccine-related decision making. Methods. Participants were girls (N = 33)
      who had received an HPV vaccine and their mothers (N = 32), recruited from
      suburban and urban pediatric practices. Semistructured interviews were conducted
      with girls and mothers separately, and data were analyzed using framework
      analysis. Results. The primary factors influencing mothers' decisions to
      vaccinate daughters against HPV were (a) mother's beliefs and experiences; (b)
      interactions with clinicians, friends, and family members; and (c) exposure to
      media reports/marketing. Most daughters believed the decision to be vaccinated
      was a mutual one, although most mothers believed the decision was theirs.
      Conclusions. This study provides novel insights into perspectives on decision
      making about HPV vaccination among mothers and 11- to12-year-old daughters, which
      can be used in interventions to improve vaccination rates.

PMID- 22589479
TI  - Fever and abdominal pain in a 5-year-old traveler.

PMID- 22589481
TI  - Progress in pediatric cancer.

PMID- 22589482
TI  - Genetically InFormed therapies--a "GIFT" for children with cancer.
AB  - The national investment that was made in oncology research with the passage of
      the National Cancer Act in 1971 is now coming to fruition. Nowhere is this more
      apparent than in the exciting prospects for genetically informed precision
      medicine as applied to the treatment of children with cancer. The wealth of
      information gleaned from intensive genetic analyses and NexGen sequencing studies
      has identified a number of viable targets in leukemias and solid tumors. Our
      rapidly evolving understanding of the enzymatic controls that regulate chromatin
      dynamics during normal differentiation of stem cells and their mutation or
      dysregulation in tumor cells is leading to a new library of therapeutically
      tractable tumor targets. The recent identification of germline variants
      associated with toxicity and/or response to therapy has further enhanced our
      ability to deliver individualized treatments for pediatric cancer patients. Our
      challenge today is to determine how best to use genomic data and integrate it
      into evolving clinical protocols to provide more efficacious therapies and a
      better quality of life for children with cancer.

PMID- 22589483
TI  - Promising therapeutic targets in neuroblastoma.
AB  - Neuroblastoma, the most common extracranial solid tumor in children, is derived
      from neural crest cells. Nearly half of patients present with metastatic disease
      and have a 5-year event-free survival of <50%. New approaches with targeted
      therapy may improve efficacy without increased toxicity. In this review we
      evaluate 3 promising targeted therapies: (i) (131)I-metaiodobenzylguanidine
      (MIBG), a radiopharmaceutical that is taken up by human norepinephrine
      transporter (hNET), which is expressed in 90% of neuroblastomas; (ii)
      immunotherapy with monoclonal antibodies targeting the GD2 ganglioside, which is
      expressed on 98% of neuroblastoma cells; and (iii) inhibitors of anaplastic
      lymphoma kinase (ALK), a tyrosine kinase that is mutated or amplified in ~10% of
      neuroblastomas and expressed on the surface of most neuroblastoma cells. Early
      phase trials have confirmed the activity of (131)I-MIBG in relapsed
      neuroblastoma, with response rates of ~30%, but the technical aspects of
      administering large amounts of radioactivity in young children and limited access
      to this agent have hindered its incorporation into treatment of newly diagnosed
      patients. Anti-GD2 antibodies have also shown activity in relapsed disease, and a
      recent phase III randomized trial showed a significant improvement in event-free
      survival for patients receiving chimeric anti-GD2 (ch14.18) combined with
      cytokines and isotretinoin after myeloablative consolidation therapy. A recently
      approved small-molecule inhibitor of ALK has shown promising preclinical activity
      for neuroblastoma and is currently in phase I and II trials. This is the first
      agent directed to a specific mutation in neuroblastoma, and marks a new step
      toward personalized therapy for neuroblastoma. Further clinical development of
      targeted treatments offers new hope for children with neuroblastoma.

PMID- 22589484
TI  - Advances in the genetics of high-risk childhood B-progenitor acute lymphoblastic
      leukemia and juvenile myelomonocytic leukemia: implications for therapy.
AB  - Hematologic malignancies of childhood comprise the most common childhood cancers.
      These neoplasms derive from the pathologic clonal expansion of an abnormal cancer
      initiating cell and span a diverse spectrum of phenotypes, including acute
      lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), myeloproliferative
      neoplasms (MPN), and myelodysplastic syndromes (MDS). Expansion of immature
      lymphoid or myeloid blasts with suppression of normal hematopoiesis is the
      hallmark of ALL and AML, whereas MPN is associated with proliferation of 1 or
      more lineages that retain the ability to differentiate, and MDS is characterized
      by abnormal hematopoiesis and cytopenias. The outcomes for children with the most
      common childhood cancer, B-progenitor ALL (B-ALL), in general, is quite
      favorable, in contrast to children affected by myeloid malignancies. The advent
      of highly sensitive genomic technologies reveals the remarkable genetic
      complexity of multiple subsets of high-risk B-progenitor ALL, in contrast to a
      somewhat simpler model of myeloid neoplasms, although a number of recently
      discovered alterations displayed by both types of malignancies may lead to common
      therapeutic approaches. This review outlines recent advances in our understanding
      of the genetic underpinnings of high-risk B-ALL and juvenile myelomonocytic
      leukemia, an overlap MPN/MDS found exclusively in children, and we also discuss
      novel therapeutic approaches that are currently being tested in clinical trials.
      Recent insights into the clonal heterogeneity of leukemic samples and the
      implications for diagnostic and therapeutic approaches are also discussed.

PMID- 22589485
TI  - Epigenetic changes in pediatric solid tumors: promising new targets.
AB  - Cancer is being reinterpreted in the light of recent discoveries related to the
      histone code and the dynamic nature of epigenetic regulation and control of gene
      programs during development, as well as insights gained from whole cancer genome
      sequencing. Somatic mutations in or deregulated expression of genes that encode
      chromatin-modifying enzymes are being identified with high frequency. Nowhere is
      this more relevant than in pediatric embryonal solid tumors. A picture is
      emerging that shows that classic genetic alterations associated with these tumors
      ultimately converge on the epigenome to dysregulate developmental programs. In
      this review, we relate how alterations in components of the transcriptional
      machinery and chromatin modifier genes contribute to the initiation and
      progression of pediatric solid tumors. We also discuss how dramatic progress in
      our understanding of the fundamental mechanisms that contribute to epigenetic
      deregulation in cancer is providing novel avenues for targeted cancer therapy.

PMID- 22589487
TI  - Using germline genomics to individualize pediatric cancer treatments.
AB  - The amazing successes in cure rates for children with cancer over the last
      century have come in large part from identifying clinical, genetic, and molecular
      variables associated with response to therapy in large cooperative clinical
      trials and stratifying therapies according to the predicted risk of relapse.
      There is an expanding interest in identifying germline genomic variants, as
      opposed to genetic variants within the tumor, that are associated with
      susceptibility to toxicity and for risk of relapse. This review highlights the
      most important germline pharmacogenetic and pharmacogenomic studies in pediatric
      oncology. Incorporating germline genomics into risk-adapted therapies will likely
      lead to safer and more effective treatments for children with cancer.

PMID- 22589488
TI  - Global methylation profiling for risk prediction of prostate cancer.
AB  - PURPOSE: The aim of this study was to investigate the promoter hypermethylation
      as diagnostic markers to detect malignant prostate cells and as prognostic
      markers to predict the clinical recurrence of prostate cancer. EXPERIMENTAL
      DESIGN: DNA was isolated from prostate cancer and normal adjacent tissues. After
      bisulfite conversion, methylation of 14,495 genes was evaluated using the
      Methylation27 microarrays in 238 prostate tissues. We analyzed methylation
      profiles in four different groups: (i) tumor (n = 198) versus matched normal
      tissues (n = 40), (ii) recurrence (n = 123) versus nonrecurrence (n = 75), (iii)
      clinical recurrence (n = 80) versus biochemical recurrence (n = 43), and (iv)
      systemic recurrence (n = 36) versus local recurrence (n = 44). Group 1, 2, 3, and
      4 genes signifying biomarkers for diagnosis, prediction of recurrence, clinical
      recurrence, and systemic progression were determined. Univariate and multivariate
      analyses were conducted to predict risk of recurrence. We validated the
      methylation of genes in 20 independent tissues representing each group by
      pyrosequencing. RESULTS: Microarray analysis revealed significant methylation of
      genes in four different groups of prostate cancer tissues. The sensitivity and
      specificity of methylation for 25 genes from 1, 2, and 4 groups and 7 from group
      3 were shown. Validation of genes by pyrosequencing from group 1 (GSTP1, HIF3A,
      HAAO, and RARbeta), group 2 (CRIP1, FLNC, RASGRF2, RUNX3, and HS3ST2), group 3
      (PHLDA3, RASGRF2, and TNFRSF10D), and group 4 (BCL11B, POU3F3, and RASGRF2)
      confirmed the microarray results. CONCLUSIONS: Our study provides a global
      assessment of DNA methylation in prostate cancer and identifies the significance
      of genes as diagnostic and progression biomarkers of prostate cancer.

PMID- 22589486
TI  - The future is now: chimeric antigen receptors as new targeted therapies for
      childhood cancer.
AB  - Improved outcomes for children with cancer hinge on the development of new
      targeted therapies with acceptable short-term and long-term toxicity. Progress in
      basic, preclinical, and clinical arenas spanning cellular immunology, gene
      therapy, and cell-processing technologies have paved the way for clinical
      applications of chimeric antigen receptor-based therapies. This is a new form of
      targeted immunotherapy that merges the exquisite targeting specificity of
      monoclonal antibodies with the potent cytotoxicity, potential for expansion, and
      long-term persistence provided by cytotoxic T cells. Although this field is still
      in its infancy, clinical trials have already shown clinically significant
      antitumor activity in neuroblastoma, chronic lymphocytic leukemia, and B-cell
      lymphoma, and trials targeting a variety of other adult and pediatric
      malignancies are under way. Ongoing work is focused on identifying optimal tumor
      targets and elucidating and manipulating both cell- and host-associated factors
      to support expansion and persistence of the genetically engineered cells in vivo.
      In pediatric oncology, CD19 and GD2 are compelling antigens that have already
      been identified for targeting pre-B acute lymphoblastic leukemia and
      neuroblastoma, respectively, with this approach, but it is likely that other
      antigens expressed in a variety of childhood cancers will also soon be targeted
      using this therapy. The potential to target essentially any tumor-associated cell
      surface antigen for which a monoclonal antibody can be made opens up an entirely
      new arena for targeted therapy of childhood cancer.

PMID- 22589489
TI  - Counterpoint: Hypobaric hypoxia does not induce different responses from
      normobaric hypoxia.

PMID- 22589490
TI  - Rebuttal from Millet, Faiss, and Pialoux.

PMID- 22589491
TI  - Rebuttal from Mounier and Brugniaux.

PMID- 22589493
TI  - Last word on Point: Counterpoint: Hypobaric hypoxia induces different responses
      from normobaric hypoxia.

PMID- 22589492
TI  - Comments on Point:Counterpoint: Hypobaric hypoxia induces/does not induce
      different responses from normobaric hypoxia.

PMID- 22589494
TI  - Last word on Counterpoint: Hypobaric hypoxia does not induce different
      physiological responses from normobaric hypoxia.

PMID- 22589495
TI  - Hemoglobin mass response to simulated hypoxia "blinded" by noisy measurement?

PMID- 22589497
TI  - Maintenance drugs to treat opioid dependence.

PMID- 22589498
TI  - Action on Hearing Loss needs your support.

PMID- 22589499
TI  - Defining the fingertip unit.

PMID- 22589501
TI  - Strengthening primary healthcare in India: white paper on opportunities for
      partnership.

PMID- 22589500
TI  - Effectiveness of dementia follow-up care by memory clinics or general
      practitioners: randomised controlled trial.
AB  - OBJECTIVE: To examine the effectiveness of post-diagnosis dementia treatment and
      coordination of care by memory clinics compared with general practitioners.
      DESIGN: Multicentre randomised controlled trial. SETTING: Nine memory clinics and
      159 general practitioners in the Netherlands. PARTICIPANTS: 175 patients with a
      new diagnosis of mild to moderate dementia living in the community and their
      informal caregivers. INTERVENTIONS: Usual care provided by memory clinic or
      general practitioner. MAIN OUTCOME MEASURES: Caregiver rated quality of life of
      the patient measured with the quality of life in Alzheimer's disease instrument
      and self perceived burden of the informal caregiver measured with the sense of
      competence questionnaire (intention to treat analysis). RESULTS: The quality of
      life of the patients in the memory clinic group was 0.5 (95% confidence interval 
      0.7 to 1.6) points higher than in the general practitioner group. Caregivers'
      burden was 2.4 (-5.8 to 1.0) points lower in the memory clinic group than in the
      general practitioner group. CONCLUSION: No evidence was found that memory clinics
      were more effective than general practitioners with regard to post-diagnosis
      treatment and coordination care for patients with dementia. Without further
      evidence on the effectiveness of these modalities, other arguments, such as cost
      minimisation, patients' preferences, or regional health service planning, can
      determine which type of dementia care is offered. TRIAL REGISTRATION: Clinical
      trials NCT00554047.

PMID- 22589502
TI  - A 64 year old woman with headache and breathlessness.

PMID- 22589503
TI  - The risks of reducing current salt levels.

PMID- 22589504
TI  - Policy change on VZIG in the US to match UK recommendations.

PMID- 22589505
TI  - We need to move away from relying on drugs to prevent lifestyle induced chronic
      disease.

PMID- 22589506
TI  - Editorial ignored 17 reviews on wind turbines and health.

PMID- 22589508
TI  - Time for rapid testing for streptococcus B during labour.

PMID- 22589509
TI  - Existing classes of antibiotics are probably the best we will ever have.

PMID- 22589510
TI  - Towards greater transparency in the life sciences.

PMID- 22589511
TI  - Facts were not entirely correct.

PMID- 22589512
TI  - Surgical application of smartphones.

PMID- 22589513
TI  - Group B Strep Support replies to Margaret McCartney.

PMID- 22589514
TI  - Don't ignore preventive message of baby Jayden's case.

PMID- 22589515
TI  - Strengthening primary healthcare in India.

PMID- 22589516
TI  - Insecticide resistance threatens malaria control programmes, WHO says.

PMID- 22589517
TI  - Medicine is our vocation.

PMID- 22589518
TI  - EU law forces UK ministers to rethink food labelling.

PMID- 22589519
TI  - Should childhood vaccination be mandatory? Yes.

PMID- 22589520
TI  - Should childhood vaccination be mandatory? No.

PMID- 22589521
TI  - Food policies for healthy populations and healthy economies.

PMID- 22589522
TI  - Taxing unhealthy food and drinks to improve health.

PMID- 22589523
TI  - Three fatal intoxications due to methylone.
AB  - We present three fatal intoxications of methylone, a cathinone derivative. Blood
      was analyzed with a routine alkaline liquid-liquid extraction and analyzed by gas
      chromatography coupled with a mass spectrometer (GC-MS). Methylone was identified
      by a full scan mass spectral comparison to an analytical standard of methylone.
      For a definitive and conclusive confirmation and quantitation, methylone was also
      derivatized with heptafluorobutyric anhydride and analyzed by GC-MS. In all three
      fatalities, the deceased exhibited seizure-like activity and elevated body
      temperatures (103.9, 105.9 and 107 degrees F) before death. Two of the three
      cases also exhibited metabolic acidosis. One of the three cases had prolonged
      treatment and hospitalization before death with symptoms similar to
      sympathomimetic toxicity, including metabolic acidosis, rhabdomyolysis, acute
      renal failure and disseminated intravascular coagulation. The laboratory results
      for this patient over the 24 h period of hospitalization were significant for
      increased lactate, liver transaminases, creatinine, myoglobin, creatine kinase
      and clotting times, and decreased pH, glucose and calcium. Peripheral blood
      methylone concentrations in the three fatal cases were 0.84, 3.3 and 0.56 mg/L.
      In conlusion, peripheral blood methylone concentrations in excess of 0.5 mg/L may
      result in death due to its toxic properties, which can include elevated body
      temperature and other sympathomimetic-like symptoms.

PMID- 22589525
TI  - Allocation of NHS resources: are some patients more equal than others?

PMID- 22589524
TI  - Psychomotor performance, subjective and physiological effects and whole blood
      Delta9-tetrahydrocannabinol concentrations in heavy, chronic cannabis smokers
      following acute smoked cannabis.
AB  - Delta9-Tetrahydrocannabinol (THC) is the illicit drug most frequently observed in
      accident and driving under the influence of drugs investigations. Whole blood is
      often the only available specimen collected during such investigations, yet few
      studies have examined relationships between cannabis effects and whole blood
      concentrations following cannabis smoking. Nine male and one female heavy,
      chronic cannabis smokers resided on a closed research unit and smoked ad libitum
      one 6.8% THC cannabis cigarette. THC, 11-hydroxy-THC and 11-nor-9-carboxy-THC
      were quantified in whole blood and plasma. Assessments were performed before and
      up to 6 h after smoking, including subjective [visual analog scales (VAS) and
      Likert scales], physiological (heart rate, blood pressure and respirations) and
      psychomotor (critical-tracking and divided-attention tasks) measures. THC
      significantly increased VAS responses and heart rate, with concentration-effect
      curves demonstrating counter-clockwise hysteresis. No significant differences
      were observed for critical-tracking or divided-attention task performance in this
      cohort of heavy, chronic cannabis smokers. The cannabis influence factor was not
      suitable for quantifying psychomotor impairment following cannabis consumption
      and was not precise enough to determine recent cannabis use with accuracy. These
      data inform our understanding of impairment and subjective effects following
      acute smoked cannabis and interpretation of whole blood cannabinoid
      concentrations in forensic investigations.

PMID- 22589526
TI  - Can a simple blood test really predict breast cancer?

PMID- 22589527
TI  - Netherlands tops European healthcare league, with UK coming in at 12th.

PMID- 22589528
TI  - EU tightens drug safety law before it is even implemented.

PMID- 22589529
TI  - Device regulator is told to improve its safety monitoring after breast implant
      debacle.

PMID- 22589530
TI  - UK doctors vote on industrial action for first time in 37 years.

PMID- 22589531
TI  - Pfizer Australia faces scrutiny over atorvastatin advertising campaign.

PMID- 22589532
TI  - A system-wide challenge for UK food policy.

PMID- 22589533
TI  - Molecular determinants of Gem protein inhibition of P/Q-type Ca2+ channels.
AB  - The RGK family of monomeric GTP-binding proteins potently inhibits high voltage
      activated Ca(2+) channels. The molecular mechanisms of this inhibition are
      largely unclear. In Xenopus oocytes, Gem suppresses the activity of P/Q-type
      Ca(2+) channels on the plasma membrane. This is presumed to occur through direct
      interactions of one or more Gem inhibitory sites and the pore-forming Ca(v)2.1
      subunit in a manner dependent on the Ca(2+) channel subunit beta (Ca(v)beta). In
      this study we investigated the molecular determinants in Gem that are critical
      for this inhibition. Like other RGK proteins, Gem contains a conserved Ras-like
      core and extended N and C termini. A 12-amino acid fragment in the C terminus was
      found to be crucial for and sufficient to produce Ca(v)beta-dependent inhibition,
      suggesting that this region forms an inhibitory site. A three-amino acid motif in
      the core was also found to be critical, possibly forming another inhibitory site.
      Mutating either site individually did not hamper Gem inhibition, but mutating
      both sites together completely abolished Gem inhibition without affecting Gem
      protein expression level or disrupting Gem interaction with Ca(v)2.1 or
      Ca(v)beta. Mutating Gem residues that are crucial for interactions with
      previously demonstrated RGK modulators such as calmodulin, 14-3-3, and
      phosphatidylinositol lipids did not significantly affect Gem inhibition. These
      results suggest that Gem contains two candidate inhibitory sites, each capable of
      producing full inhibition of P/Q-type Ca(2+) channels.

PMID- 22589534
TI  - Discovery of a novel allosteric modulator of 5-HT3 receptors: inhibition and
      potentiation of Cys-loop receptor signaling through a conserved transmembrane
      intersubunit site.
AB  - The ligand-gated ion channels in the Cys-loop receptor superfamily mediate the
      effects of neurotransmitters acetylcholine, serotonin, GABA, and glycine. Cys
      loop receptor signaling is susceptible to modulation by ligands acting through
      numerous allosteric sites. Here we report the discovery of a novel class of
      negative allosteric modulators of the 5-HT(3) receptors (5-HT(3)Rs). PU02 (6-[(1
      naphthylmethyl)thio]-9H-purine) is a potent and selective antagonist displaying
      IC(50) values of ~1 MUM at 5-HT(3)Rs and substantially lower activities at other
      Cys-loop receptors. In an elaborate mutagenesis study of the 5-HT(3)A receptor
      guided by a homology model, PU02 is demonstrated to act through a transmembrane
      intersubunit site situated in the upper three helical turns of TM2 and TM3 in the
      (+)-subunit and TM1 and TM2 in the (-)-subunit. The Ser(248), Leu(288), Ile(290),
      Thr(294), and Gly(306) residues are identified as important molecular
      determinants of PU02 activity with minor contributions from Ser(292) and
      Val(310), and we propose that the naphthalene group of PU02 docks into the
      hydrophobic cavity formed by these. Interestingly, specific mutations of
      Ser(248), Thr(294), and Gly(306) convert PU02 into a complex modulator,
      potentiating and inhibiting 5-HT-evoked signaling through these mutants at low
      and high concentrations, respectively. The PU02 binding site in the 5-HT(3)R
      corresponds to allosteric sites in anionic Cys-loop receptors, which emphasizes
      the uniform nature of the molecular events underlying signaling through the
      receptors. Moreover, the dramatic changes in the functional properties of PU02
      induced by subtle changes in its binding site bear witness to the delicate
      structural discrimination between allosteric inhibition and potentiation of Cys
      loop receptors.

PMID- 22589535
TI  - Tissue-specific and nutrient regulation of the branched-chain alpha-keto acid
      dehydrogenase phosphatase, protein phosphatase 2Cm (PP2Cm).
AB  - Branched-chain amino acid (BCAA) homeostasis is maintained through highly
      regulated catabolic activities where the rate-limiting step is catalyzed by
      branched-chain alpha-keto dehydrogenase (BCKD). Our previous study has identified
      a mitochondria-targeted protein phosphatase, PP2Cm, as the BCKD phosphatase and
      thus serves as a key regulator for BCAA catabolism. In this report, we performed
      comprehensive molecular and biochemical studies of PP2Cm regulation using both in
      vivo and in vitro systems. We show that PP2Cm expression is highly enriched in
      brain, heart, liver, kidney, and diaphragm, but low in skeletal muscle. The PP2Cm
      expression is regulated at the transcriptional level in response to nutrient
      status. Furthermore, we have established that PP2Cm interacts with the BCKD E2
      subunit and competes with the BCKD kinase in a substrate-dependent and mutually
      exclusive manner. These data suggest that BCAA homeostasis is at least in part
      contributed by nutrient-dependent PP2Cm expression and interaction with the BCKD
      complex. Finally, a number of human PP2Cm single nucleotide polymorphic changes
      as identified in the public data base can produce either inactive or constitutive
      active mutant phosphatases, suggesting that putative PP2Cm mutations may
      contribute to BCAA catabolic defects in human.

PMID- 22589536
TI  - Activation of Wnt/beta-catenin protein signaling induces mitochondria-mediated
      apoptosis in hematopoietic progenitor cells.
AB  - The canonical Wnt/beta-catenin signaling is activated during development,
      tumorigenesis, and in adult homeostasis, yet its role in maintenance of
      hematopoietic stem/progenitor cells is not firmly established. Here, we
      demonstrate that conditional expression of an active form of beta-catenin in vivo
      induces a marked increase in the frequency of apoptosis in hematopoietic
      stem/progenitor cells (HSCs/HPCs). Activation of Wnt/beta-catenin signaling in
      HPCs in vitro elevates the activity of caspases 3 and 9 and leads to a loss of
      mitochondrial membrane potential (DeltaPsi(m)), indicating that it induces the
      intrinsic mitochondrial apoptotic pathway. In vivo, expression of activated beta
      catenin in HPCs is associated with down-regulation of Bcl2 and expression of
      Casp3. Bone marrow transplantation assays reveal that enhanced cell survival by a
      Bcl2 transgene re-establishes the reconstitution capacity of HSCs/HPCs that
      express activated beta-catenin. In addition, a Bcl2 transgene prevents exhaustion
      of these HSCs/HPCs in vivo. Our data suggest that activation of the Wnt/beta
      catenin pathway contributes to the defective function of HPCs in part by
      deregulating their survival.

PMID- 22589538
TI  - Significant impact of single N-glycan residues on the biological activity of Fc
      based antibody-like fragments.
AB  - Recent studies have demonstrated that IgG-Fc fragments (Fcabs) can be engineered
      to form antigen-binding sites with antibody properties. Thus they may serve as an
      attractive alternative to conventional antibodies in therapeutic applications.
      The critical influence of Fc glycosylation on effector functions of IgGs is well
      documented; however, whether this applies to Fcabs is not known. Here we used
      human cells, wild type, and glycoengineered plants to generate four different
      glycoforms of H10-03-6, an Fcab with engineered HER2/neu-binding sites. Plant
      derived H10-03-6 differed in the presence/absence of single oligosaccharide
      residues, i.e., core fucose and xylose, and terminal galactose. All of the
      glycoforms had similar binding to HER2/neu expressed on human tumor cells. By
      contrast, glycoforms that lacked core oligosaccharide modifications (i.e., core
      alpha1,3-fucose and beta1,2-xylose) showed significantly enhanced binding to the
      Fcgamma receptor IIIa, irrespective of whether plant or human expression systems
      were used. Consistent with this finding, plant-derived H10-03-6 glycoforms
      lacking core N-glycan residues mediated higher antibody-dependent cellular
      cytotoxicity against human tumor cells. No alteration in gamma-receptor binding
      and antibody-dependent cellular cytotoxicity activity was observed upon
      decoration of N-glycans by terminal galactose. The results point to a significant
      impact of distinct N-glycan residues on effector functions of Fcabs. Moreover,
      the outcomes imply that the effector functions mediated by H10-03-6 can be
      optimized by altering the N-glycosylation profile. Biasing vaccine-induced immune
      responses toward optimal Fc glycosylation patterns could result in improved
      vaccine efficacy.

PMID- 22589537
TI  - Elevated cyclin G2 expression intersects with DNA damage checkpoint signaling and
      is required for a potent G2/M checkpoint arrest response to doxorubicin.
AB  - To maintain genomic integrity DNA damage response (DDR), signaling pathways have
      evolved that restrict cellular replication and allow time for DNA repair. CCNG2
      encodes an unconventional cyclin homolog, cyclin G2 (CycG2), linked to growth
      inhibition. Its expression is repressed by mitogens but up-regulated during cell
      cycle arrest responses to anti-proliferative signals. Here we investigate the
      potential link between elevated CycG2 expression and DDR signaling pathways.
      Expanding our previous finding that CycG2 overexpression induces a p53-dependent
      G(1)/S phase cell cycle arrest in HCT116 cells, we now demonstrate that this
      arrest response also requires the DDR checkpoint protein kinase Chk2. In accord
      with this finding we establish that ectopic CycG2 expression increases
      phosphorylation of Chk2 on threonine 68. We show that DNA double strand break
      inducing chemotherapeutics stimulate CycG2 expression and correlate its up
      regulation with checkpoint-induced cell cycle arrest and phospho-modification of
      proteins in the ataxia telangiectasia mutated (ATM) and ATM and Rad3-related
      (ATR) signaling pathways. Using pharmacological inhibitors and ATM-deficient cell
      lines, we delineate the DDR kinase pathway promoting CycG2 up-regulation in
      response to doxorubicin. Importantly, RNAi-mediated blunting of CycG2 attenuates
      doxorubicin-induced cell cycle checkpoint responses in multiple cell lines.
      Employing stable clones, we test the effect that CycG2 depletion has on DDR
      proteins and signals that enforce cell cycle checkpoint arrest. Our results
      suggest that CycG2 contributes to DNA damage-induced G(2)/M checkpoint by
      enforcing checkpoint inhibition of CycB1-Cdc2 complexes.

PMID- 22589539
TI  - Mediation of the antiapoptotic activity of Bcl-xL protein upon interaction with
      VDAC1 protein.
AB  - The mitochondrial protein, the voltage-dependent anion channel (VDAC), is
      implicated in the control of apoptosis, including via its interaction with the
      pro- and antiapoptotic proteins. We previously demonstrated the direct
      interaction of Bcl2 with VDAC, leading to reduced channel conductance. VDAC1
      based peptides interacted with Bcl2 to prevent its antiapoptotic activity. Here,
      using a variety of approaches, we show the interaction of the antiapoptotic
      protein, Bcl-xL, with VDAC1 and reveal that this interaction mediates Bcl-xL
      protection against apoptosis. C-terminally truncated Bcl-xL(Delta21) interacts
      with purified VDAC1, as revealed by microscale thermophoresis and as reflected in
      the reduced channel conductivity of bilayer-reconstituted VDAC1. Overexpression
      of Bcl-xL prevented staurosporine-induced apoptosis in cells expressing native
      VDAC1 but not certain VDAC1 mutants. Having identified mutations in VDAC1 that
      interfere with the Bcl-xL interaction, certain peptides representing VDAC1
      sequences, including the N-terminal domain, were designed and generated as
      recombinant and synthetic peptides. The VDAC1 N-terminal region and two internal
      sequences were found to bind specifically, and in a concentration- and time
      dependent manner, to immobilized Bcl-xL(Delta21), as revealed by surface plasmon
      resonance. Moreover, expression of the recombinant peptides in cells
      overexpressing Bcl-xL prevented protection offered by the protein against
      staurosporine-induced apoptosis. These results point to Bcl-xL acting as
      antiapoptotic protein, promoting tumor cell survival via binding to VDAC1. These
      findings suggest that interfering with Bcl-xL binding to the mitochondria by
      VDAC1-based peptides may serve to induce apoptosis in cancer cells and to
      potentiate the efficacy of conventional chemotherapeutic agents.

PMID- 22589540
TI  - Tyrosine kinase Btk is required for NK cell activation.
AB  - Bruton tyrosine kinase (Btk) is not only critical for B cell development and
      differentiation but is also involved in the regulation of Toll-like receptor
      triggered innate response of macrophages. However, whether Btk is involved in the
      regulation of natural killer (NK) cell innate function remains unknown. Here, we
      show that Btk expression is up-regulated during maturation and activation of
      mouse NK cells. Murine Btk(-/-) NK cells have decreased innate immune responses
      to the TLR3 ligand, with reduced expressions of IFN-gamma, perforin, and granzyme
      B and decreased cytotoxic activity. Furthermore, Btk is found to promote TLR3
      triggered NK cell activation mainly by activating the NF-kappaB pathway.
      Poly(I:C)-induced NK cell-mediated acute hepatitis was observed to be attenuated
      in Btk(-/-) mice or the mice with in vivo administration of the Btk inhibitor.
      Correspondingly, liver damage was aggravated in Btk(-/-) mice after the adoptive
      transfer of Btk(+/+) NK cells, further indicating that Btk-mediated NK cell
      activation contributes to TLR3-triggered acute liver injury. Importantly, reduced
      TLR3-triggered activation of human NK cells was observed in Btk-deficient
      patients with X-linked agammaglobulinemia, as evidenced by the reduced IFN-gamma,
      CD69, and CD107a expression and cytotoxic activity. These results indicate that
      Btk is required for activation of NK cells, thus providing insight into the
      physiological significance of Btk in the regulation of immune cell functions and
      innate inflammatory response.

PMID- 22589541
TI  - Promyelocytic leukemia protein (PML) regulates endothelial cell network formation
      and migration in response to tumor necrosis factor alpha (TNFalpha) and
      interferon alpha (IFNalpha).
AB  - Promyelocytic leukemia protein (PML) is a tumor suppressor that is highly
      expressed in vascular endothelium and inflamed tissues, yet its role in
      inflammation-associated cytokine-regulated angiogenesis and underlying mechanism
      remains largely unclear. We show that tumor necrosis factor alpha (TNFalpha) and
      interferon alpha (IFNalpha) stimulate PML expression while suppressing EC network
      formation and migration, two key events during angiogenesis. By a knockdown
      approach, we demonstrate that PML is indispensable for TNFalpha- and IFNalpha
      mediated inhibition of EC network formation. We further demonstrate that signal
      transducer and activator of transcription 1 (STAT1) binds PML promoter and that
      is an important regulator of PML expression. Knockdown of STAT1 reduces
      endogenous PML and blocks TNFalpha- and IFNalpha-induced PML accumulation and
      relieves TNFalpha- and IFNalpha-mediated inhibition of EC network formation. Our
      data also indicate that PML regulates EC migration, in part, by modulating
      expression of downstream genes, such as negatively regulating integrin beta1
      (ITGB1). In addition, knockdown of STAT1 or PML alleviates TNFalpha- and IFNalpha
      mediated inhibition of ITGB1 expression. Antibody blockade demonstrates that
      ITGB1 is functionally important for PML- and STAT1-regulated EC migration. Taken
      together, our data provide novel mechanistic insights that PML functions as a
      negative regulator in EC network formation and migration.

PMID- 22589542
TI  - Solid-state NMR reveals a close structural relationship between amyloid-beta
      protofibrils and oligomers.
AB  - We have studied tertiary contacts in protofibrils and mature fibrils of amyloid
      beta (Abeta) peptides using solid-state NMR spectroscopy. Although intraresidue
      contacts between Glu-22 and Ile-31 were found in Abeta protofibrils, these
      contacts were completely absent in mature Abeta fibrils. This is consistent with
      the current models of mature Abeta fibrils. As these intramolecular contacts have
      also been reported in Abeta oligomers, our measurements suggest that Abeta
      protofibrils are structurally more closely related to oligomers than to mature
      fibrils. This suggests that some structural alterations have to take place on the
      pathway from Abeta oligomers/protofibrils to mature fibrils, in agreement with a
      model that suggests a conversion of intramolecular hydrogen-bonded structures of
      Abeta oligomers to the intermolecular stabilized mature fibrils (Hoyer, W.,
      Gronwall, C., Jonsson, A., Stahl, S., and Hard, T. (2008) Proc. Natl. Acad. Sci.
      U.S.A. 105, 5099-5104).

PMID- 22589543
TI  - LST1/A is a myeloid leukocyte-specific transmembrane adaptor protein recruiting
      protein tyrosine phosphatases SHP-1 and SHP-2 to the plasma membrane.
AB  - Transmembrane adaptor proteins are membrane-anchored proteins consisting of a
      short extracellular part, a transmembrane domain, and a cytoplasmic part with
      various protein-protein interaction motifs but lacking any enzymatic activity.
      They participate in the regulation of various signaling pathways by recruiting
      other proteins to the proximity of cellular membranes where the signaling is
      often initiated and propagated. In this work, we show that LST1/A, an
      incompletely characterized protein encoded by MHCIII locus, is a palmitoylated
      transmembrane adaptor protein. It is expressed specifically in leukocytes of the
      myeloid lineage, where it localizes to the tetraspanin-enriched microdomains. In
      addition, it binds SHP-1 and SHP-2 phosphatases in a phosphotyrosine-dependent
      manner, facilitating their recruitment to the plasma membrane. These data suggest
      a role for LST1/A in negative regulation of signal propagation.

PMID- 22589544
TI  - A competitive inhibitor that reduces recruitment of androgen receptor to androgen
      responsive genes.
AB  - The androgen receptor (AR) has a critical role in the growth and progression of
      androgen-dependent and castration-resistant prostate cancers. To identify novel
      inhibitors of AR transactivation that block growth of prostate cancer cells, a
      luciferase-based high-throughput screen of ~160,000 small molecules was performed
      in cells stably expressing AR and a prostate-specific antigen (PSA)-luciferase
      reporter. CPIC (1-(3-(2-chlorophenoxy) propyl)-1H-indole-3-carbonitrile) was
      identified as a small molecule that blocks AR transactivation to a greater extent
      than other steroid receptors. CPIC inhibited AR-mediated proliferation of
      androgen-sensitive prostate cancer cell lines, with minimal toxicity in AR
      negative cell lines. CPIC treatment also reduced the anchorage-independent growth
      of LAPC-4 prostate cancer cells. CPIC functioned as a pure antagonist by
      inhibiting the expression of AR-regulated genes in LAPC-4 cells that express wild
      type AR and exhibited weak agonist activity in LNCaP cells that express the
      mutant AR-T877A. CPIC treatment did not reduce AR levels or alter its nuclear
      localization. We used chromatin immunoprecipitation to identify the site of
      action of CPIC. CPIC inhibited recruitment of androgen-bound AR to the PSA
      promoter and enhancer sites to a greater extent than bicalutamide. CPIC is a new
      therapeutic inhibitor that targets AR-mediated gene activation with potential to
      arrest the growth of prostate cancer.

PMID- 22589545
TI  - Molecular insights into the function of RING finger (RNF)-containing proteins
      hRNF8 and hRNF168 in Ubc13/Mms2-dependent ubiquitylation.
AB  - The repair of DNA double strand breaks by homologous recombination relies on the
      unique topology of the chains formed by Lys-63 ubiquitylation of chromatin to
      recruit repair factors such as breast cancer 1 (BRCA1) to sites of DNA damage.
      The human RING finger (RNF) E3 ubiquitin ligases, RNF8 and RNF168, with the E2
      ubiquitin-conjugating complex Ubc13/Mms2, perform the majority of Lys-63
      ubiquitylation in homologous recombination. Here, we show that RNF8 dimerizes and
      binds to Ubc13/Mms2, thereby stimulating formation of Lys-63 ubiquitin chains,
      whereas the related RNF168 RING domain is a monomer and does not catalyze Lys-63
      polyubiquitylation. The crystal structure of the RNF8/Ubc13/Mms2 ternary complex
      reveals the structural basis for the interaction between Ubc13 and the RNF8 RING
      and that an extended RNF8 coiled-coil is responsible for its dimerization.
      Mutations that disrupt the RNF8/Ubc13 binding surfaces, or that truncate the RNF8
      coiled-coil, reduce RNF8-catalyzed ubiquitylation. These findings support the
      hypothesis that RNF8 is responsible for the initiation of Lys-63-linked
      ubiquitylation in the DNA damage response, which is subsequently amplified by
      RNF168.

PMID- 22589546
TI  - Crystal structure of the acyltransferase domain of the iterative polyketide
      synthase in enediyne biosynthesis.
AB  - Biosynthesis of the enediyne natural product dynemicin in Micromonospora chersina
      is initiated by DynE8, a highly reducing iterative type I polyketide synthase
      that assembles polyketide intermediates from the acetate units derived solely
      from malonyl-CoA. To understand the substrate specificity and the evolutionary
      relationship between the acyltransferase (AT) domains of DynE8, fatty acid
      synthase, and modular polyketide synthases, we overexpressed a 44-kDa fragment of
      DynE8 (hereafter named AT(DYN10)) encompassing its entire AT domain and the
      adjacent linker domain. The crystal structure at 1.4 A resolution unveils a
      alpha/beta hydrolase and a ferredoxin-like subdomain with the Ser-His catalytic
      dyad located in the cleft between the two subdomains. The linker domain also
      adopts a alpha/beta fold abutting the AT catalytic domain. Co-crystallization
      with malonyl-CoA yielded a malonyl-enzyme covalent complex that most likely
      represents the acyl-enzyme intermediate. The structure explains the preference
      for malonyl-CoA with a conserved arginine orienting the carboxylate group of
      malonate and several nonpolar residues that preclude alpha-alkyl malonyl-CoA
      binding. Co-crystallization with acetyl-CoA revealed two noncovalently bound
      acetates generated by the enzymatic hydrolysis of acetyl-CoA that acts as an
      inhibitor for DynE8. This suggests that the AT domain can upload the acyl groups
      from either malonyl-CoA or acetyl-CoA onto the catalytic Ser(651) residue.
      However, although the malonyl group can be transferred to the acyl carrier
      protein domain, transfer of the acetyl group to the acyl carrier protein domain
      is suppressed. Local structural differences may account for the different
      stability of the acyl-enzyme intermediates.

PMID- 22589547
TI  - Mutation of the calmodulin binding motif IQ of the L-type Ca(v)1.2 Ca2+ channel
      to EQ induces dilated cardiomyopathy and death.
AB  - Cardiac excitation-contraction coupling (EC coupling) links the electrical
      excitation of the cell membrane to the mechanical contractile machinery of the
      heart. Calcium channels are major players of EC coupling and are regulated by
      voltage and Ca(2+)/calmodulin (CaM). CaM binds to the IQ motif located in the C
      terminus of the Ca(v)1.2 channel and induces Ca(2+)-dependent inactivation (CDI)
      and facilitation (CDF). Mutation of Ile to Glu (Ile1624Glu) in the IQ motif
      abolished regulation of the channel by CDI and CDF. Here, we addressed the
      physiological consequences of such a mutation in the heart. Murine hearts
      expressing the Ca(v)1.2(I1624E) mutation were generated in adult heterozygous
      mice through inactivation of the floxed WT Ca(v)1.2(L2) allele by tamoxifen
      induced cardiac-specific activation of the MerCreMer Cre recombinase. Within 10
      days after the first tamoxifen injection these mice developed dilated
      cardiomyopathy (DCM) accompanied by apoptosis of cardiac myocytes (CM) and
      fibrosis. In Ca(v)1.2(I1624E) hearts, the activity of phospho-CaM kinase II and
      phospho-MAPK was increased. CMs expressed reduced levels of Ca(v)1.2(I1624E)
      channel protein and I(Ca). The Ca(v)1.2(I1624E) channel showed "CDI" kinetics.
      Despite a lower sarcoplasmic reticulum Ca(2+) content, cellular contractility and
      global Ca(2+) transients remained unchanged because the EC coupling gain was up
      regulated by an increased neuroendocrine activity. Treatment of mice with
      metoprolol and captopril reduced DCM in Ca(v)1.2(I1624E) hearts at day 10. We
      conclude that mutation of the IQ motif to IE leads to dilated cardiomyopathy and
      death.

PMID- 22589548
TI  - Deletion of the C-terminal phosphorylation sites in the cardiac beta-subunit does
      not affect the basic beta-adrenergic response of the heart and the Ca(v)1.2
      channel.
AB  - Phosphorylation of the cardiac beta subunit (Ca(v)beta(2)) of the Ca(v)1.2 L-type
      Ca(2+) channel complex has been proposed as a mechanism for regulation of L-type
      Ca(2+) channels by various protein kinases including PKA, CaMKII, Akt/PKB, and
      PKG. To test this hypothesis directly in vivo, we generated a knock-in mouse line
      with targeted mutation of the Ca(v)beta(2) gene by insertion of a stop codon
      after proline 501 in exon 14 (mouse sequence Cacnb2; betaStop mouse). This
      mutation prevented translation of the Ca(v)beta(2) C terminus that contains the
      relevant phosphorylation sites for the above protein kinases. Homozygous cardiac
      betaStop mice were born at Mendelian ratio, had a normal life expectancy, and
      normal basal L-type I(Ca). The regulation of the L-type current by stimulation of
      the beta-adrenergic receptor was unaffected in vivo and in cardiomyocytes (CMs).
      betaStop mice were cross-bred with mice expressing the Ca(v)1.2 gene containing
      the mutation S1928A (SAbetaStop) or S1512A and S1570A (SFbetaStop) in the C
      terminus of the alpha(1C) subunit. The beta-adrenergic regulation of the cardiac
      I(Ca) was unaltered in these mouse lines. In contrast, truncation of the Ca(v)1.2
      at Asp(1904) abolished beta-adrenergic up-regulation of I(Ca) in murine embryonic
      CMs. We conclude that phosphorylation of the C-terminal sites in Ca(v)beta(2),
      Ser(1928), Ser(1512), and Ser(1570) of the Ca(v)1.2 protein is functionally not
      involved in the adrenergic regulation of the murine cardiac Ca(v)1.2 channel.

PMID- 22589549
TI  - Anks4b, a novel target of HNF4alpha protein, interacts with GRP78 protein and
      regulates endoplasmic reticulum stress-induced apoptosis in pancreatic beta
      cells.
AB  - Mutations of the HNF4A gene cause a form of maturity-onset diabetes of the young
      (MODY1) that is characterized by impairment of pancreatic beta-cell function.
      HNF4alpha is a transcription factor belonging to the nuclear receptor superfamily
      (NR2A1), but its target genes in pancreatic beta-cells are largely unknown. Here,
      we report that ankyrin repeat and sterile alpha motif domain containing 4b
      (Anks4b) is a target of HNF4alpha in pancreatic beta-cells. Expression of Anks4b
      was decreased in both betaHNF4alpha KO islets and HNF4alpha knockdown MIN6 beta
      cells, and HNF4alpha activated Anks4b promoter activity. Anks4b bound to glucose
      regulated protein 78 (GRP78), a major endoplasmic reticulum (ER) chaperone
      protein, and overexpression of Anks4b enhanced the ER stress response and ER
      stress-associated apoptosis of MIN6 cells. Conversely, suppression of Anks4b
      reduced beta-cell susceptibility to ER stress-induced apoptosis. These results
      indicate that Anks4b is a HNF4alpha target gene that regulates ER stress in beta
      cells by interacting with GRP78, thus suggesting that HNF4alpha is involved in
      maintenance of the ER.

PMID- 22589550
TI  - HIRA, a conserved histone chaperone, plays an essential role in low-dose stress
      response via transcriptional stimulation in fission yeast.
AB  - Cells that have been pre-exposed to mild stress (priming stress) acquire
      transient resistance to subsequent severe stress even under different
      combinations of stresses. This phenomenon is called cross-tolerance. Although it
      has been reported that cross-tolerance occurs in many organisms, the molecular
      basis is not clear yet. Here, we identified slm9(+) as a responsible gene for the
      cross-tolerance in the fission yeast Schizosaccharomyces pombe. Slm9 is a homolog
      of mammalian HIRA histone chaperone. HIRA forms a conserved complex and gene
      disruption of other HIRA complex components, Hip1, Hip3, and Hip4, also yielded a
      cross-tolerance-defective phenotype, indicating that the fission yeast HIRA is
      involved in the cross-tolerance as a complex. We also revealed that Slm9 was
      recruited to the stress-responsive gene loci upon stress treatment in an Atf1
      dependent manner. The expression of stress-responsive genes under stress
      conditions was compromised in HIRA disruptants. Consistent with this, Pol II
      recruitment and nucleosome eviction at these gene loci were impaired in slm9Delta
      cells. Furthermore, we found that the priming stress enhanced the expression of
      stress-responsive genes in wild-type cells that were exposed to the severe
      stress. These observations suggest that HIRA functions in stress response through
      transcriptional regulation.

PMID- 22589551
TI  - The atypical histone macroH2A1.2 interacts with HER-2 protein in cancer cells.
AB  - Because HER-2 has been demonstrated in the nuclei of cancer cells, we
      hypothesized that it might interact with transcription factors that activate
      ERBB2 transcription. Macrohistone 2A1 (H2AFY; mH2A1) was found to interact with
      HER-2 in cancer cells that overexpress HER-2. Of the two human mH2A1 isoforms,
      mH2A1.2, but not mH2A1.1, interacted with HER-2 in human cancer cell lines.
      Overexpression of mH2A1.2, but not mH2A1.1, in cancer cells significantly
      increased HER-2 expression and tumorigenicity. Inhibition of HER-2 kinase
      activity diminished mH2A1 expression and mH2A1.2-induced ERBB2 transcription in
      cancer cells. Chromatin immunoprecipitation of mH2A1.2 in cancer cells stably
      transfected with mH2A1.2 showed enrichment of mH2A1.2 at the HER-2 promoter,
      suggesting a role for mH2A1.2 in driving HER-2 overexpression. The evolutionarily
      conserved macro domain of mH2A1.2 was sufficient for the interaction between HER
      2 and mH2A1.2 and for mH2A1.2-induced ERBB2 transcription. Within the macro
      domain of mH2A1.2, a trinucleotide insertion (-EIS-) sequence not found in
      mH2A1.1 was essential for the interaction between HER-2 and mH2A1.2 as well as
      mH2A1.2-induced HER-2 expression and cell proliferation.

PMID- 22589552
TI  - Epstein-Barr nuclear antigen 1 (EBNA1)-dependent recruitment of origin
      recognition complex (Orc) on oriP of Epstein-Barr virus with purified proteins:
      stimulation by Cdc6 through its direct interaction with EBNA1.
AB  - Origin recognition complex (Orc) plays an essential role in directing assembly of
      prereplicative complex at selective sites on chromosomes. However, Orc from
      vertebrates is reported to bind to DNA in a sequence-nonspecific manner, and it
      is still unclear how it selects specific genomic loci and how Cdc6, another
      conserved AAA(+) factor known to interact with Orc, participates in this process.
      Replication from oriP, the latent origin of Epstein-Barr virus, provides an
      excellent model system for the study of initiation on the host chromosomes
      because it is known to depend on prereplicative complex factors, including Orc
      and Mcm. Here, we show that Orc is recruited selectively at the essential dyad
      symmetry element in nuclear extracts in a manner dependent on EBNA1, which
      specifically binds to dyad symmetry. With purified proteins, EBNA1 can recruit
      both Cdc6 and Orc independently on a DNA containing EBNA1 binding sites, and Cdc6
      facilitates the Orc recruitment by EBNA1. Purified Cdc6 directly binds to EBNA1,
      whereas association of Orc with EBNA1 requires the presence of the oriP DNA.
      Nuclease protection assays suggest that Orc associates with DNA segments on both
      sides adjacent to the EBNA1 binding sites and that this process is stimulated by
      the presence of Cdc6. Thus, EBNA1 can direct localized assembly of Orc in a
      process that is facilitated by Cdc6. The possibility of similar modes of
      recruitment of Orc/Cdc6 at the human chromosomal origins will be discussed.

PMID- 22589553
TI  - Tight interplay among SAMHD1 protein level, cellular dNTP levels, and HIV-1
      proviral DNA synthesis kinetics in human primary monocyte-derived macrophages.
AB  - Recently, SAMHD1 has come under intense focus as a host anti-HIV factor. SAMHD1
      is a dNTP triphosphohydrolase, which leads to the regulation of DNA metabolism in
      host cells. HIV-2/SIV (simian immunodeficiency virus) viral protein x (Vpx) has
      been shown to promote the degradation of SAMHD1. In this study, we examine the
      kinetics of SAMHD1 degradation, the increase in the dNTP pool level, and the
      efficiency of proviral DNA synthesis in Vpx+ virus-like particle (VLP)-treated
      monocyte-derived macrophages (MDMs). Our results indicate a very close temporal
      link with a reduction in SAMHD1 detected within the first few hours of Vpx+ VLP
      treatment. This loss of SAMHD1 is followed by a significant increase in cellular
      dNTP levels by 8 h after Vpx+ VLP addition, ultimately leading to the enhancement
      of the HIV proviral DNA synthesis rate and HIV infection in MDMs. Finally, the
      pretreatment of MDMs with the Vpx+ VLPs, which is a widely used protocol,
      displayed identical proviral DNA synthesis as compared with MDMs co-treated with
      Vpx+ VLP and HIV vector. These findings further indicate that Vpx degradation of
      SAMHD1 is sufficiently rapid to enable appropriate progression of reverse
      transcription in MDMs, even when present at the time of infection. Overall, this
      study demonstrates a tight interplay between SAMHD1 level, dNTP levels, and HIV
      proviral DNA synthesis kinetics in MDMs.

PMID- 22589554
TI  - Specific residues of a conserved domain in the N terminus of the human
      cytomegalovirus pUL50 protein determine its intranuclear interaction with pUL53.
AB  - Herpesviral capsids are assembled in the host cell nucleus and are subsequently
      translocated to the cytoplasm. During this process it has been demonstrated that
      the human cytomegalovirus proteins pUL50 and pUL53 interact and form, together
      with other viral and cellular proteins, the nuclear egress complex at the nuclear
      envelope. In this study we provide evidence that specific residues of a conserved
      N-terminal region of pUL50 determine its intranuclear interaction with pUL53. In
      silico evaluation and biophysical analyses suggested that the conserved region
      forms a regular secondary structure adopting a globular fold. Importantly, site
      directed replacement of individual amino acids by alanine indicated a strong
      functional influence of specific residues inside this globular domain. In
      particular, mutation of the widely conserved residues Glu-56 or Tyr-57 led to a
      loss of interaction with pUL53. Consistent with the loss of binding properties,
      mutants E56A and Y57A showed a defective function in the recruitment of pUL53 to
      the nuclear envelope in expression plasmid-transfected and human cytomegalovirus
      infected cells. In addition, in silico analysis suggested that residues 3-20 form
      an amphipathic alpha-helix that appears to be conserved among Herpesviridae.
      Point mutants revealed a structural role of this N-terminal alpha-helix for pUL50
      stability rather than a direct role in the binding of pUL53. In contrast, the
      central part of the globular domain including Glu-56 and Tyr-57 is directly
      responsible for the functional interaction with pUL53 and thus determines
      formation of the basic nuclear egress complex.

PMID- 22589556
TI  - Phylogeography and demographic history of the neotropical otter (Lontra
      longicaudis).
AB  - The Neotropical otter (Lontra longicaudis) is a medium-sized semiaquatic
      carnivore with a broad distribution in the Neotropical region. Despite being
      apparently common in many areas, it is one of the least known otters, and genetic
      studies on this species are scarce. Here, we have investigated its genetic
      diversity, population structure, and demographic history across a large portion
      of its geographic range by analyzing 1471 base pairs (bp) of mitochondrial DNA
      from 52 individuals. Our results indicate that L. longicaudis presents high
      levels of genetic diversity and a consistent phylogeographic pattern, suggesting
      the existence of at least 4 distinct evolutionary lineages in South America. The
      observed phylogeographic partitions are partially congruent with the subspecies
      classification previously proposed for this species. Coalescence-based analyses
      indicate that Neotropical otter mitochondrial DNA lineages have shared a rather
      recent common ancestor, approximately 0.5 Ma, and have subsequently diversified
      into the observed phylogroups. A consistent scenario of recent population
      expansion was identified in Eastern South America based on several complementary
      analyses of historical demography. The results obtained here provide novel
      insights on the evolutionary history of this largely unknown Neotropical mustelid
      and should be useful to design conservation and management policies on behalf of
      this species and its habitats.

PMID- 22589557
TI  - Macrophage SR-BI regulates LPS-induced pro-inflammatory signaling in mice and
      isolated macrophages.
AB  - Scavenger receptor BI (SR-BI), an HDL receptor, plays a key role in reverse
      cholesterol transport. In mice, disruption of SR-BI results in hypersensitivity
      to lipopolysaccharide (LPS) and bacteria-induced septic shock due to adrenal
      insufficiency and abnormal hepatic pathogen clearance. In this study, we identify
      an anti-inflammatory role of macrophage SR-BI. Using bone marrow transplantation,
      we report an enhanced pro-inflammatory response to LPS in wild-type (WT) mice
      receiving SR-BI-null compared with WT bone marrow cells and a reduced response in
      SR-BI-null mice receiving WT compared with SR-BI-null cells. Although
      significant, SR-BI deficiency limited to bone marrow-derived cells promoted a
      relatively modest enhancement of the inflammatory response to LPS in mice
      compared with the effect of whole-body SR-BI deletion. Consistent with earlier
      findings, SR-BI-null primary macrophages exhibited a greater inflammatory
      cytokine response to LPS than control macro phages. In addition, we showed that
      overexpression of SR-BI in J774 macrophages attenuated the inflammatory response
      to LPS. The LPS-induced cytokine expression in both WT and SR-BI-null macrophages
      was dependent not only on NFkappaB as previously reported but also on JNK and P38
      cell signaling pathways. The increased inflammatory signaling in SR-BI-null cells
      was not related to alterations in cellular cholesterol content. We conclude that
      SR-BI plays an important function in regulating the macrophage inflammatory
      response to LPS.

PMID- 22589560
TI  - Establishing an evidence base for e-health: the proof is in the pudding.

PMID- 22589558
TI  - Preservation of biological function despite oxidative modification of the
      apolipoprotein A-I mimetic peptide 4F.
AB  - Myeloperoxidase (MPO)-derived hypochlorous acid induces changes in HDL function
      via redox modifications at the level of apolipoprotein A-I (apoA-I). As 4F and
      apoA-I share structural and functional properties, we tested the hypothesis that
      4F acts as a reactive substrate for hypochlorous acid (HOCl). 4F reduced the HOCl
      mediated oxidation of the fluorescent substrate APF in a concentration-dependent
      manner (ED(50) ~ 56 +/- 3 MUM). This reaction induced changes in the physical
      properties of 4F. Addition of HOCl to 4F at molar ratios ranging from 1:1 to 3:1
      reduced 4F band intensity on SDS-PAGE gels and was accompanied by the formation
      of a higher molecular weight species. Chromatographic studies showed a reduction
      in 4F peak area with increasing HOCl and the formation of new products. Mass
      spectral analyses of collected fractions revealed oxidation of the sole
      tryptophan (Trp) residue in 4F. 4F was equally susceptible to oxidation in the
      lipid-free and lipid-bound states. To determine whether Trp oxidation influenced
      its apoA-I mimetic properties, we monitored effects of HOCl on 4F-mediated lipid
      binding and ABCA1-dependent cholesterol efflux. Neither property was altered by
      HOCl. These results suggest that 4F serves as a reactive substrate for HOCl, an
      antioxidant response that does not influence the lipid binding and cholesterol
      effluxing capacities of the peptide.

PMID- 22589561
TI  - Improving the credibility of electronic health technologies.

PMID- 22589563
TI  - Measuring the impact of e-health.

PMID- 22589564
TI  - E-health's future frontiers.

PMID- 22589565
TI  - The bigger picture for e-health.

PMID- 22589566
TI  - E-health in low- and middle-income countries: findings from the Center for Health
      Market Innovations.
AB  - OBJECTIVE: To describe how information communication technology (ICT) is being
      used by programmes that seek to improve private sector health financing and
      delivery in low- and middle-income countries, including the main uses of the
      technology and the types of technologies being used. METHODS: In-country partners
      in 16 countries directly searched systematically for innovative health programmes
      and compiled profiles in the Center for Health Market Innovations' database.
      These data were supplemented through literature reviews and with self-reported
      data supplied by the programmes themselves. FINDINGS: In many low- and middle
      income countries, ICT is being increasingly employed for different purposes in
      various health-related areas. Of ICT-enabled health programmes, 42% use it to
      extend geographic access to health care, 38% to improve data management and 31%
      to facilitate communication between patients and physicians outside the
      physician's office. Other purposes include improving diagnosis and treatment
      (17%), mitigating fraud and abuse (8%) and streamlining financial transactions
      (4%). The most common devices used in technology-enabled programmes are phones
      and computers; 71% and 39% of programmes use them, respectively, and the most
      common applications are voice (34%), software (32%) and text messages (31%).
      Donors are the primary funders of 47% of ICT-based health programmes. CONCLUSION:
      Various types of ICT are being employed by private organizations to address key
      health system challenges. For successful implementation, however, more
      sustainable sources of funding, greater support for the adoption of new
      technologies and better ways of evaluating impact are required.

PMID- 22589567
TI  - Long-running telemedicine networks delivering humanitarian services: experience,
      performance and scientific output.
AB  - OBJECTIVE: To summarize the experience, performance and scientific output of long
      running telemedicine networks delivering humanitarian services. METHODS: Nine
      long-running networks--those operating for five years or more--were identified
      and seven provided detailed information about their activities, including
      performance and scientific output. Information was extracted from peer-reviewed
      papers describing the networks' study design, effectiveness, quality, economics,
      provision of access to care and sustainability. The strength of the evidence was
      scored as none, poor, average or good. FINDINGS: The seven networks had been
      operating for a median of 11 years (range: 5-15). All networks provided clinical
      tele-consultations for humanitarian purposes using store-and-forward methods and
      five were also involved in some form of education. The smallest network had 15
      experts and the largest had more than 500. The clinical caseload was 50 to 500
      cases a year. A total of 59 papers had been published by the networks, and 44
      were listed in Medline. Based on study design, the strength of the evidence was
      generally poor by conventional standards (e.g. 29 papers described non-controlled
      clinical series). Over half of the papers provided evidence of sustainability and
      improved access to care. Uncertain funding was a common risk factor. CONCLUSION:
      Improved collaboration between networks could help attenuate the lack of
      resources reported by some networks and improve sustainability. Although the
      evidence base is weak, the networks appear to offer sustainable and clinically
      useful services. These findings may interest decision-makers in developing
      countries considering starting, supporting or joining similar telemedicine
      networks.

PMID- 22589568
TI  - Early infant diagnosis of HIV infection in Zambia through mobile phone texting of
      blood test results.
AB  - OBJECTIVE: To see if, in the diagnosis of infant infection with human
      immunodeficiency virus (HIV) in Zambia, turnaround times could be reduced by
      using an automated notification system based on mobile phone texting. METHODS: In
      Zambia's Southern province, dried samples of blood from infants are sent to
      regional laboratories to be tested for HIV with polymerase chain reaction (PCR).
      Turnaround times for the postal notification of the results of such tests to 10
      health facilities over 19 months were evaluated by retrospective data collection.
      These baseline data were used to determine how turnaround times were affected by
      customized software built to deliver the test results automatically and directly
      from the processing laboratory to the health facility of sample origin via short
      message service (SMS) texts. SMS system data were collected over a 7.5-month
      period for all infant dried blood samples used for HIV testing in the 10 study
      facilities. FINDINGS: Mean turnaround time for result notification to a health
      facility fell from 44.2 days pre-implementation to 26.7 days post-implementation.
      The reduction in turnaround time was statistically significant in nine (90%)
      facilities. The mean time to notification of a caregiver also fell significantly,
      from 66.8 days pre-implementation to 35.0 days post-implementation. Only 0.5% of
      the texted reports investigated differed from the corresponding paper reports.
      CONCLUSION: The texting of the results of infant HIV tests significantly
      shortened the times between sample collection and results notification to the
      relevant health facilities and caregivers.

PMID- 22589569
TI  - Factors that promote or inhibit the implementation of e-health systems: an
      explanatory systematic review.
AB  - OBJECTIVE: To systematically review the literature on the implementation of e
      health to identify: (i) barriers and facilitators to e-health implementation, and
      (ii) outstanding gaps in research on the subject. METHODS: MEDLINE, EMBASE,
      CINAHL, PSYCINFO and the Cochrane Library were searched for reviews published
      between 1 January 1995 and 17 March 2009. Studies had to be systematic reviews,
      narrative reviews, qualitative metasyntheses or meta-ethnographies of e-health
      implementation. Abstracts and papers were double screened and data were extracted
      on country of origin; e-health domain; publication date; aims and methods;
      databases searched; inclusion and exclusion criteria and number of papers
      included. Data were analysed qualitatively using normalization process theory as
      an explanatory coding framework. FINDINGS: Inclusion criteria were met by 37
      papers; 20 had been published between 1995 and 2007 and 17 between 2008 and 2009.
      Methodological quality was poor: 19 papers did not specify the inclusion and
      exclusion criteria and 13 did not indicate the precise number of articles
      screened. The use of normalization process theory as a conceptual framework
      revealed that relatively little attention was paid to: (i) work directed at
      making sense of e-health systems, specifying their purposes and benefits,
      establishing their value to users and planning their implementation; (ii) factors
      promoting or inhibiting engagement and participation; (iii) effects on roles and
      responsibilities; (iv) risk management, and (v) ways in which implementation
      processes might be reconfigured by user-produced knowledge. CONCLUSION: The
      published literature focused on organizational issues, neglecting the wider
      social framework that must be considered when introducing new technologies.

PMID- 22589571
TI  - Improving patient access to specialized health care: the Telehealth Network of
      Minas Gerais, Brazil.
AB  - PROBLEM: The Brazilian population lacks equitable access to specialized health
      care and diagnostic tests, especially in remote municipalities, where health
      professionals often feel isolated and staff turnover is high. Telehealth has the
      potential to improve patients' access to specialized health care, but little is
      known about it in terms of cost-effectiveness, access to services or user
      satisfaction. APPROACH: In 2005, the State Government of Minas Gerais, Brazil,
      funded the establishment of the Telehealth Network, intended to connect
      university hospitals with the state's remote municipal health departments;
      support professionals in providing tele-assistance; and perform tele
      electrocardiography and teleconsultations. The network uses low-cost equipment
      and has employed various strategies to overcome the barriers to telehealth use.
      LOCAL SETTING: The Telehealth Network connects specialists in state university
      hospitals with primary health-care professionals in 608 municipalities of the
      large state of Minas Gerais, many of them in remote areas. RELEVANT CHANGES: From
      June 2006 to October 2011, 782,773 electrocardiograms and 30 883
      teleconsultations were performed through the network, and 6000 health
      professionals were trained in its use. Most of these professionals (97%) were
      satisfied with the system, which was cost-effective, economically viable and
      averted 81% of potential case referrals to distant centres. LESSONS LEARNT: To
      succeed, a telehealth service must be part of a collaborative network, meet the
      real needs of local health professionals, use simple technology and have at least
      some face-to-face components. If applied to health problems for which care is in
      high demand, this type of service can be economically viable and can help to
      improve patient access to specialized health care.

PMID- 22589570
TI  - Impacts of e-health on the outcomes of care in low- and middle-income countries:
      where do we go from here?
AB  - E-health encompasses a diverse set of informatics tools that have been designed
      to improve public health and health care. Little information is available on the
      impacts of e-health programmes, particularly in low- and middle-income countries.
      We therefore conducted a scoping review of the published and non-published
      literature to identify data on the effects of e-health on health outcomes and
      costs. The emphasis was on the identification of unanswered questions for future
      research, particularly on topics relevant to low- and middle-income countries.
      Although e-health tools supporting clinical practice have growing penetration
      globally, there is more evidence of benefits for tools that support clinical
      decisions and laboratory information systems than for those that support picture
      archiving and communication systems. Community information systems for disease
      surveillance have been implemented successfully in several low- and middle-income
      countries. Although information on outcomes is generally lacking, a large project
      in Brazil has documented notable impacts on health-system efficiency. Meta
      analyses and rigorous trials have documented the benefits of text messaging for
      improving outcomes such as patients' self-care. Automated telephone monitoring
      and self-care support calls have been shown to improve some outcomes of chronic
      disease management, such as glycaemia and blood pressure control, in low- and
      middle-income countries. Although large programmes for e-health implementation
      and research are being conducted in many low- and middle-income countries, more
      information on the impacts of e-health on outcomes and costs in these settings is
      still needed.

PMID- 22589572
TI  - Improving quality and use of data through data-use workshops: Zanzibar, United
      Republic of Tanzania.
AB  - PROBLEM: In Zanzibar, United Republic of Tanzania, as in many developing
      countries, health managers lack faith in the national Health Management
      Information System (HMIS). The establishment of parallel data collection systems
      generates a vicious cycle: national health data are used little because they are
      of poor quality, and their relative lack of use, in turn, makes their quality
      remain poor. APPROACH: An action research approach was applied to strengthen the
      use of information and improve data quality in Zanzibar. The underlying premise
      was that encouraging use in small incremental steps could help to break the
      vicious cycle and improve the HMIS. LOCAL SETTING: To test the hypothesis at the
      national and district levels a project to strengthen the HMIS was established in
      Zanzibar. The project included quarterly data-use workshops during which district
      staff assessed their own routine data and critiqued their colleagues' data.
      RELEVANT CHANGES: The data-use workshops generated inputs that were used by
      District Health Information Software developers to improve the tool. The HMIS,
      which initially covered only primary care outpatients and antenatal care,
      eventually grew to encompass all major health programmes and district and
      referral hospitals. The workshops directly contributed to improvements in data
      coverage, data set quality and rationalization, and local use of target
      indicators. LESSONS LEARNT: Data-use workshops with active engagement of data
      users themselves can improve health information systems overall and enhance staff
      capacity for information use, presentation and analysis for decision-making.

PMID- 22589573
TI  - Short message service sentinel surveillance of influenza-like illness in
      Madagascar, 2008-2012.
AB  - PROBLEM: The revision of the International Health Regulations (IHR) and the
      threat of influenza pandemics and other disease outbreaks with a major impact on
      developing countries have prompted bolstered surveillance capacity, particularly
      in low-resource settings. APPROACH: Surveillance tools with well-timed, validated
      data are necessary to strengthen disease surveillance. In 2007 Madagascar
      implemented a sentinel surveillance system for influenza-like illness (ILI) based
      on data collected from sentinel general practitioners. SETTING: Before 2007,
      Madagascar's disease surveillance was based on the passive collection and
      reporting of data aggregated weekly or monthly. The system did not allow for the
      early identification of outbreaks or unexpected increases in disease incidence.
      RELEVANT CHANGES: An innovative case reporting system based on the use of cell
      phones was launched in March 2007. Encrypted short message service, which costs
      less than 2 United States dollars per month per health centre, is now being used
      by sentinel general practitioners for the daily reporting of cases of fever and
      ILI seen in their practices. To validate the daily data, practitioners also
      report epidemiological and clinical data (e.g. new febrile patient's sex, age,
      visit date, symptoms) weekly to the epidemiologists on the research team using
      special patient forms. LESSONS LEARNT: Madagascar's sentinel ILI surveillance
      system represents the country's first nationwide "real-time" surveillance system.
      It has proved the feasibility of improving disease surveillance capacity through
      innovative systems despite resource constraints. This type of syndromic
      surveillance can detect unexpected increases in the incidence of ILI and other
      syndromic illnesses.

PMID- 22589574
TI  - M-health for health behaviour change in resource-limited settings: applications
      to HIV care and beyond.

PMID- 22589575
TI  - Point of care in your pocket: a research agenda for the field of m-health.

PMID- 22589576
TI  - Successful partnerships for international collaboration in e-health: the need for
      organized national infrastructures.

PMID- 22589577
TI  - Securing the public good of health research and development for developing
      countries.

PMID- 22589578
TI  - Dynamic change in respiratory resistance during inspiratory and expiratory phases
      of tidal breathing in patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is
      characterized by persistent airflow limitation consisting of airway obstruction
      and parenchymal emphysema, with loss of elastic recoil. The forced oscillation
      technique can detect impairment of lung function by measuring lung impedance
      during normal tidal breathing. Respiratory resistance (Rrs) in COPD has been well
      studied, but the differences in Rrs in the inspiratory and expiratory phases
      between mild and moderate COPD remain poorly understood. Since airway obstruction
      in COPD is known to change dynamically during tidal breathing and might affect
      Rrs, the differences in Rrs during tidal breathing between mild and moderate COPD
      were evaluated. METHODS: Mild (n = 13) and moderate (n = 13) COPD patients were
      recruited at Tokyo University Hospital (Tokyo, Japan). Rrs was measured using
      MostGraph-01 (Chest MI, Inc, Tokyo, Japan), which depicted Rrs in a frequency-and
      respiratory cycle-dependent manner in three-dimensional graphics. Rrs was
      evaluated at 4-35 Hz during tidal breathing. RESULTS: Rrs changed dynamically
      during tidal breathing in COPD. The mean Rrs values were significantly greater in
      the moderate COPD group than in the mild group. The maximal and minimal Rrs
      values at higher frequencies in the respiratory cycle were significantly greater
      in moderate COPD. In inspiratory-expiratory breath analysis, the maximal and
      minimal Rrs values at 20 Hz and 35 Hz were significantly greater in the moderate
      group, whereas at 4 Hz they did not differ significantly between the groups.
      CONCLUSION: Rrs changed dynamically during tidal breathing in patients with COPD.
      The Rrs values at higher frequencies were greater in moderate COPD than in mild
      COPD. Rrs at higher frequencies might reflect the degree of airway obstruction in
      tidal breathing in patients with COPD and might be a useful marker for evaluation
      of airway obstruction at an early stage of COPD.

PMID- 22589579
TI  - Sputum eosinophilia can predict responsiveness to inhaled corticosteroid
      treatment in patients with overlap syndrome of COPD and asthma.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) and asthma may overlap
      and converge in older people (overlap syndrome). It was hypothesized that
      patients with overlap syndrome may have different clinical characteristics such
      as sputum eosinophilia, and better responsiveness to treatment with inhaled
      corticosteroid (ICS). METHODS: Sixty-three patients with stable COPD (forced
      expiratory volume in 1 second [FEV(1)] <=80%) underwent pulmonary function tests,
      including reversibility of airflow limitation, arterial blood gas analysis,
      analysis of inflammatory cells in induced sputum, and chest high-resolution
      computed tomography. The inclusion criteria for COPD patients with asthmatic
      symptoms included having asthmatic symptoms such as episodic breathlessness,
      wheezing, cough, and chest tightness worsening at night or in the early morning
      (COPD with asthma group). The clinical features of COPD patients with asthmatic
      symptoms were compared with those of COPD patients without asthmatic symptoms
      (COPD without asthma group). RESULTS: The increases in FEV(1) in response to
      treatment with ICS were significantly higher in the COPD with asthma group. The
      peripheral eosinophil counts and sputum eosinophil counts were significantly
      higher. The prevalence of patients with bronchial wall thickening on chest high
      resolution computed tomography was significantly higher. A significant
      correlation was observed between the increases in FEV(1) in response to treatment
      with ICS and sputum eosinophil counts, and between the increases in FEV(1) in
      response to treatment with ICS and the grade of bronchial wall thickening.
      Receiver operating characteristic curve analysis revealed 82.4% sensitivity and
      84.8% specificity of sputum eosinophil count for detecting COPD with asthma,
      using 2.5% as the cutoff value. CONCLUSION: COPD patients with asthmatic symptoms
      had some clinical features. ICS should be considered earlier as a potential
      treatment in such patients. High sputum eosinophil counts and bronchial wall
      thickening on chest high-resolution computed tomography might therefore be a good
      predictor of response to ICS.

PMID- 22589580
TI  - Evaluation of the restoration success of endodontic therapy of the primary
      molars.
AB  - OBJECTIVES: The aim of this study was to evaluate the clinical and radiographic
      success rates of pulpotomized primary molar teeth restored with a compomer
      material with using United States Public Health Service (USPHS) criteria.
      METHODS: In 173 primary molars of 156 child patients, aged within 4-9 years (mean
      age: 6.1+/-1.4 years), conventional pulpotomy treatment were performed. The teeth
      treated using calcium hydroxide, formocresol or ferric sulphate. After pulpotomy
      procedure, teeth were restored with compomer material. The teeth were evaluated
      as clinically and radiographically during a period of 12-24 months. Both of
      success of pulpotomy treatment and also restorative material (compomer material)
      were evaluated during follow-up period. The data were assessed with chi-square
      test. RESULTS: At the end of the first year, 45% of initial treated teeth were
      checked, but only 18% were checked at the end of the second year. The first year
      success rates in the groups treated with CH, FC, and FS were 87.5%, 95%, and 79%,
      respectively, and, as the number of controllable patients was lower, the success
      rates on available teeth were determined to be 88.3% and 80%, respectively,
      according to the materials at the end of the second year. Restorations having
      been made, they were analyzed in accordance with USPHS criteria. CONCLUSIONS: At
      the end of the first year, 67.5% of compomer restorations were detected to be
      original and healthy and at the end of the second year, 57% were deemed healthy.
      No statistically significant relationships were found between marginal
      adaptation, secondary caries and pulpotomy success (chi-square test, P>.05).
      Among the three groups, there is no significant difference in terms of success.
      The least successful age group was defined as 4-6 years.

PMID- 22589581
TI  - Evaluation of the Immediate Dentofacial Changes in Late Adolescent Patients
      Treated with the Forsus(TM) FRD.
AB  - OBJECTIVES: The purpose of this study was to evaluate the short-term
      dentoalveolar and soft tissue changes in late adolescent patients treated with
      the ForsusTM FRD. METHODS: A prospective study was carried out on 54 lateral
      cephalometric radiograms that were taken before placement and after removal of
      the appliance in the treatment group (15 subjects) and at the beginning and six
      months after in the control group (12 subjects). The patient selection criteria
      were as follows: skeletal and dental Class II malocclusion due to retrognatic
      mandible, normal or low-angle growth pattern, post-peak growth period, no
      extracted or congenitally missing permanent teeth, and minimum crowding in the
      lower dental arch. RESULTS: THE STATISTICAL ASSESMENT OF THE DATA SUGGESTED THE
      FOLLOWING RESULTS: No sagital and vertical skeletal changes were induced. The
      mandibular incisors were protruded and intruded, while the maxillary incisors
      were retruded and extruded. The occlusal plane was rotated in clockwise direction
      as a result of these dentoalveolar changes. Overbite and overjet were reduced in
      all patients. Soft tissue profile slightly improved. CONCLUSIONS: The results
      revealed that, in late-adolescent patients ForsusTM FRD corrected Class II
      discrepancies through maxillary and mandibular dentoalveolar changes.

PMID- 22589582
TI  - The effect of investment materials on the color of feldspathic ceramics.
AB  - OBJECTIVES: The aim of this study was to evaluate the influence of investment
      type on the color of feldspathic ceramics. METHODS: Ceramic specimens were
      constructed using the refractory die technique, using four investments (i.e.,
      Vitadurvest, Duravest, Duceralay Superfit, and Fortune) to observe their effect
      on the color of five commercially available ceramics (i.e., Super Porcelain EX-3,
      Vision Esthetic, Vintage Halo, IPS Classic, and Vitadur Alpha). The color
      analysis of the ceramics was performed with a colorimeter using the CIE L*a*b*
      color coordinates. RESULTS: The investments produced significant alterations on
      a*, b*, and L* color parameters of the ceramics tested. The ceramic Vision
      Esthetic was influenced by the type of investment in all color parameters
      (P<.05). Two investments (Duravest and Fortune) produced alterations in color
      parameters with three of the five ceramics tested. CONCLUSIONS: The investment
      materials produced alterations on the ceramic color parameters, resulting in
      unacceptable chromatic alterations (DeltaE*).

PMID- 22589583
TI  - Continuing professional development : roles of the individual lecturer and the
      institution.

PMID- 22589584
TI  - Intra-operative frozen section consultation: concepts, applications and
      limitations.
AB  - Intra-operative frozen section plays an important role in the management of
      surgical patients and yet it must be used prudently to avoid the indiscriminate
      usage of this important technique. As it is subjected to many limitations in
      comparison to the paraffin embedded tissue sections, this review aims to
      highlight the important concepts and principle of intra-operative frozen section
      consultation as well as discussing the limitations of this technique. This will
      then allow the endusers of this technique to be more informed and more selective
      in their decisions when requesting for a frozen section report.

PMID- 22589586
TI  - Parent-adolescent relationships and its association to adolescents' self-esteem.
AB  - Psychoanalysts believed that early mother-child relationships form the prototype
      of all future relationships and the outcome of adolescents development depends on
      their ego-strength. Object relations theory believed that intrapsychic process
      mediates interpersonal interaction to develop a sense of secure self and
      adolescents must relinquish the internalized other in order to develop a more
      mature sense of self. Social-relation theory believed that mothers and fathers
      provide different socialization experiences. Self-esteem depends on the
      functioning of the whole family in which adolescent is intimately related to the
      dyadic relationship in a family. There is an association between interparental
      conflict and adolescent's self-esteem and problem behaviour.

PMID- 22589585
TI  - Cloning and expression of malaria and tuberculosis epitopes in mycobacterium
      bovis bacille calmette-guerin.
AB  - Mycobacterium bovis bacille Calmette-Guerin (BCG) represents one of the most
      promising live vectors for the delivery of foreign antigens to the immune system.
      A recombinant BCG containing a synthetic gene coding for the malarial epitopes
      namely, the fragment 2 of region II of EBA-175 (F2R(II)EBA) and the repeat
      sequence of the circumsporozoite protein NANP generated in favour of
      mycobacterium codon usage using assembly PCR was constructed. Two T-cell epitopes
      of the 6-kDa M. tuberculosis early-secreted antigenic target (ESAT-6) antigen
      were also clone in the same construct. Expression of the synthetic gene was
      driven by the heat shock protein 65 (hsp65) promoter from M. tuberculosis and the
      signal peptide from the MPT63 antigen of M. tuberculosis. Expression of the
      composite epitopes was detected by Western blotting of the cell extract and
      culture supernatant of the recombinant clones using a specific rabbit polyclonal
      antibody against F2R(II)EBA. This study demonstrates the possibility of cloning
      and expressing immunogenic epitopes from causative agents of two important
      diseases: malaria and tuberculosis (TB) in a single recombinant BCG construct.

PMID- 22589587
TI  - A cross-sectional study of soft tissue facial morphometry in children and
      adolescents.
AB  - The aim of this study was to determine mean values for selected linear
      measurements on the face of children and adolescents to demonstrate gender
      differences in the measurements. Cross-sectional data from 262 school children
      (158 male, 104 female) aged between 6 and 15 years were taken by measuring
      certain identified facial landmarks using a sliding caliper. The landmarks were
      first located by careful inspection and/or palpation of the face and a mark
      created on the cutaneous surface, with the subject sitting in habitual occlusion
      in an upright position. A sliding caliper was used to measure the distances
      between the points. The data was analysed using SPSS version 10.0 to determine
      mean values, standard deviation and gender differences in the measurements. Upper
      facial heights, total facial height, inter-canthal distance and eye length
      measurements were significantly higher in male than in female for 15-year-old
      group (p<0.0001). The measurement between the highest and the lowest point of
      attachment of external ear to the head was significantly larger in male than in
      female for 11 year old age group.

PMID- 22589588
TI  - Pattern of Sexual Offences Attended at Accident and Emergency Department of HUSM
      from Year 2000 to 2003: A Retrospective Study.
AB  - This paper investigates the pattern of sexual offence cases attended at the One
      Stop Crisis Center (OSCC) of the Accident and Emergency Department, Hospital
      Universiti Sains Malaysia (HUSM), Kelantan. A total of 439 reported sexual
      offence cases were examined over a period of 4 years from 2000 to 2003. Sexual
      offence constituted by male partner or boyfriend in 18.9%, by relatives in 27.3%
      and by "others" in 53.8% of cases. Only 0.7% of victims did not attempt to lodge
      a police report. There is a significant relationship between occupation and the
      risk of experiencing sexual violence. Students were mostly targeted by the
      perpetrator throughout the study period. Among the offences, rape cases were the
      highest in number, among those who attended at the OSCC, HUSM with a total of
      72.7%; followed by 27.3% of incest; 26.4% of child sexual abuse; 4.8% of sodomy
      and lastly 1.6% of gerontophilia cases. Only 70% of the specimens obtained from
      sexual offences victims were sent for laboratory analysis. The result remained
      negative in 82.4% specimens and thus the laboratory analysis result is merely
      functioning as a supportive evidence for sexual offence cases attended at OSCC.
      The studies showed that most of the sexual assault perpetrators were known to the
      victims. The place of crime was also known to the perpetrators. Health sectors of
      various levels should be working in conjunction to promote a societal changes to
      improve more of the women's right and thus to reduce the violence crime.

PMID- 22589589
TI  - Time delay and its effect on survival in malaysian patients with non-small cell
      lung carcinoma.
AB  - While evidence indicates that early stage disease has better prognosis, the
      effect of delay in presentation and treatment of patients with non-small cell
      lung cancer (NSCLC) on survival is debatable. A retrospective study of 122
      Malaysian patients with NSCLC was performed to examine the presentation and
      treatment delay, and its relation with patient survival. Median (25-75% IQR)
      interval between onset of symptoms and first hospital consultation (patient
      delay) and between first hospital consultation and treatment or decision to treat
      (doctor delay) were 2 (1.0- 5.0) and 1.1 (0.6-2.4) months respectively. The
      median survival rates in patient delay of <1, 1 to 3, and >3 months were 4.1 (9.9
      1.7), 5.1 (10.9-3.2) and 5.7 (12.3-2.1) months respectively (log rank p=0.648),
      while in doctor delay, <30, 30-60, >60 days, the rates were 4.1 (10.8-1.8), 7.6
      (13.7-3.2) and 5.3 (16.0-3.0) months respectively (p=0.557). Most patients
      presented and were treated in a relatively short time, and delays did not appear
      to influence survival. This Asian data is consistent with those from Western
      population, reiterating the need for public health measures that can identify
      disease early..

PMID- 22589590
TI  - Medical Standby: An Experience at the 4(th) National Youth Camping and Motivation
      Program Organized by Maksak Malaysia.
AB  - Medical standby is the provision of emergency medical care and first aid for
      participants and/or spectators in a pre-planned event. This article describes the
      framework and the demographics of a medical standby at the 4(th) National Youth
      Camping and Motivation Program in Pasir Puteh, Kelantan from 30(th) July until
      the 3(rd) August 2004. The framework of the medical team is described based on
      the work process of any medical stand by. A medical encounter form was created
      for the medical standby defining the type of case seen (medical or trauma), name,
      age, race and diagnosis of the patient. We concluded that interagency
      collaboration during the initial planning and during the event itself is needed
      to ensure the smooth running of the medical standby. Most of the medical
      encounters were minor illnesses which are similar to previous studies and there
      was no case transferred to the hospital during that period.

PMID- 22589591
TI  - Role of scintimammography in the diagnosis of breast cancer.
AB  - X-ray mammography has been the backbone of early detection of breast cancer.
      Several large scale systematic studies have shown that judicious use of X-ray
      mammography can indeed save life. However, though reasonably sensitive, X-ray
      mammography lacks in specificity leading to many unnecessary biopsies.
      Scintimammography is a relatively new imaging method to demonstrate cancer tissue
      in the breast. A radiopharmaceutical agent (Tc-99m Sestamibi) is administered
      intravenously and images of the breast are taken under a Gamma Camera. There is
      no need for any manipulation like compression of the breast as required to be
      done during mammography. The radiopharmaceutical accumulates in the breast in the
      presence of cancer tissue which can easily be seen in the images. The affinity of
      the cancer tissue to this radiopharmaceutical is up to 9 times in comparison to
      normal breast tissue. Several multi centric studies with blinded image
      interpretation have established the sensitivity and specificity of
      scintimammography to be above 85 and 90 % respectively as compared to 89 and 14 %
      respectively for X-ray mammography. The positive and negative predictive values
      of scintimamography are 70 and 83 % as against 49 and 57 % respectively for X-ray
      mammography. With the increasing availability of Nuclear Medicine facilities it
      is expected that more and more patients will benefi with the use of this new
      imaging modality .

PMID- 22589592
TI  - The Clinical Interview Schedule-Revised (CIS-R)-Malay Version, Clinical
      Validation.
AB  - Use of instruments or questionnaires in different cultural settings without
      proper validation can result in inaccurate results. Issues like reliability,
      validity, feasibility and acceptability should be considered in the use of an
      instrument. The study aims to determine the usefulness of the CIS-R Malay version
      in detecting common mental health problems specifically to establish the
      validity. The CIS-R instrument (PROQSY* format) was translated through the back
      translation process into Malay. Inter rater reliability was established for
      raters who were medical students. Cases and controls for the study were
      psychiatric in patients, out patient and relatives or friends accompanying the
      patients to the clinic or visiting the inpatients. The Malay version of CIS-R was
      administered to all cases and controls. All cases and controls involved in the
      study were rated by psychiatrists for psychiatric morbidity using the SCID as a
      guideline. Specificity and sensitivity of the CIS-R to the assessment by the
      psychiatrist were determined. The Malay version of CIS-R showed 100% sensitivity
      and 96.15% specificity at a cut off score of 9. The CIS-R can be a useful
      instrument for clinical and research use in the Malaysian population for
      diagnosing common mental disorders like depression and anxiety.

PMID- 22589593
TI  - Problem-based learning as perceived by dental students in universiti sains
      malaysia.
AB  - The implementation of problem-based learning started in 1969 and has spread since
      then throughout different parts of the world with variations in its
      implementation. In spite of its growth and advantages, there is continuing debate
      about its effectiveness over the conventional teaching learning methods. In the
      School of Dental Sciences (SDS), Universiti Sains Malaysia (USM), the Doctor of
      Dental Sciences (DDS) program follows a 5-year integrated curriculum. Basically
      the curriculum is problem-based and community oriented. This study was to explore
      the perception of DDS students about PBL sessions. This questionnaires-based
      cross sectional descriptive study were carried out on all the 110 students of the
      SDS who completed their second year of the course and participated in PBL
      sessions. Ninety five (86%) students responded to the questionnaires. Dental
      students found PBL session interesting and wanted to maintain PBL from the
      beginning of year 2 up to the end of year 3. Most students reported their
      participation in discussion during PBL sessions but the level of participation
      varied. Some of them worked hard to prepare themselves for discussion while
      others were relatively passive. PBL helped them with in-depth understanding of
      certain topics and link their basic science knowledge to clinical classes. They
      felt that guidance from subject specialists and well-prepared facilitators of the
      sessions were beneficial. The students believed that repetition of triggers from
      year to year discouraged their active search for learning issues. Majority of the
      students were undecided or disagreed about the availability of adequate learning
      resources Most of the students were undecided or disagreed about the availability
      of adequate learning resources for their self-study. Reviewing and renewing the
      PBL triggers, providing guidelines for searching for resource materials and
      briefing the students and facilitators about the philosophy and principles of PBL
      may make the PBL sessions more beneficial.

PMID- 22589594
TI  - Prevalence of Intestinal Parasites In HIV-Positive/AIDS Patients.
AB  - The aim of this study was to assess the prevalence of intestinal parasites among
      HIV-positive/AIDS patients. A control group comprising 30 apparently healthy HIV
      negative individuals was included. Of the 60 samples collected from the patients
      and examined, 34 (56.7%) presented with diarrhoea, while 26 (43.3%) had no
      reported cases of diarrhoea at the time of study. Seventeen (50%) of the
      parasites detected in the 34 patients (those with history of diarrhoea) were
      diarrhoea-related causative agents. However, 17 (50%) of the parasites detected
      were not diarrhoea-related causative agents. In relation to diarrhoea,
      Cryptosporidium parvum had the highest prevalence (10%), followed by Giardia
      intestinalis (8.3%), Entamoeba histolytica (6.7%), Isospora belli (3.3%) and
      Blastocystis hominis (3.3%) in that order. This study showed a significant
      prevalence (P<0.05) of intestinal parasites in HIV-positive/AIDS patient. Also,
      the prevalence of intestinal parasites was higher (P<0.05) in HIV-positive/AIDS
      patients than in HIV-negative subjects. Although the study is limited in scope,
      however, it does reflect the importance of evaluating the prevalence of
      intestinal parasites in HIV-positive/AIDS patients especially at the local level
      where antiretroviral therapy is not available. The results of this study thus
      provide vital information for health professionals who are managing these
      patients. This could lead to improvement in patients' management and care.

PMID- 22589596
TI  - The role of anatomists and surgeons in clinical anatomy instruction inside and
      outside the operating room.

PMID- 22589595
TI  - Typhoid and malaria co-infection - an interesting finding in the investigation of
      a tropical Fever.
AB  - In the investigation of fever in the tropics, two important diagnoses to be ruled
      out are typhoid and malaria. Both cause significant morbidity, mortality and
      economic loss. An estimated 17 million cases of typhoid are reported worldwide
      each year, resulting in 0.6 million deaths. Seventy five to eighty percent of
      these cases occur in Asia alone. Malaria affects 1 billion people each year; out
      of which 1-3 million die. Although caused by very different organisms - one a
      Gram negative bacilli, the other a protozoa, and transmitted via different
      mechanisms - ingestion of contaminated food and water and via the bite of an
      insect vector respectively, both typhoid and malaria share rather similar
      symptomatology and epidemiology. Malaysia is endemic for both these diseases and
      one should not be too surprised when faced with a diagnosis of co-infection of
      typhoid and malaria, as have been described in India and Canada. Here we describe
      one such case of Salmonella typhi and Plasmodium vivax infection.

PMID- 22589597
TI  - Of roots, barks, paracetamol and EDTA.

PMID- 22589598
TI  - About Clinicopathological Conference and Its' Practice in the School of Medical
      Sciences, USM.
AB  - The clinicopathological conference, popularly known as CPC primarily relies on
      case method of teaching medicine. It is a teaching tool that illustrates the
      logical, measured consideration of a differential diagnosis used to evaluate
      patients. The process involves case presentation, diagnostic data, discussion of
      differential diagnosis, logically narrowing the list to few selected probable
      diagnoses and eventually reaching a final diagnosis and its brief discussion. The
      idea was first practiced in Boston, back in 1900 by a Harvard internist, Dr.
      Richard C. Cabot who practiced this as an informal discussion session in his
      private office. Dr. Cabot incepted this from a resident, who in turn had received
      the idea from a roommate, primarily a law student.

PMID- 22589600
TI  - Nerve conduction study among healthy malays. The influence of age, height and
      body mass index on median, ulnar, common peroneal and sural nerves.
AB  - Nerve conduction study is essential in the diagnosis of focal neuropathies and
      diffuse polyneuropathies. Age, height and body mass index (BMI) can affect nerve
      velocities as reported by previous studies. We studied the effect of these
      factors on median, ulnar, common peroneal and sural nerves among healthy Malay
      subjects. We observed slowing of nerve conduction velocities (NCVs) with
      increasing age and BMI (except ulnar sensory velocities). No demonstrable trend
      can be seen across different height groups except in common peroneal nerve.

PMID- 22589599
TI  - The role of the thalamus in modulating pain.
AB  - The thalamus is one of the structures that receives projections from multiple
      ascending pain pathways. The structure is not merely a relay centre but is
      involved in processing nociceptive information before transmitting the
      information to various parts of the cortex. The thalamic nuclei are involved in
      the sensory discriminative and affective motivational components of pain.
      Generally each group of nucleus has prominent functions in one component for
      example ventrobasal complex in sensory discriminative component and intralaminar
      nuclei in affective-motivational component. The thalamus is also part of a
      network that projects to the spinal cord dorsal horn and modulates ascending
      nociceptive information. In the animal models of neuropathic pain, changes in the
      biochemistry, gene expression, thalamic blood flow and response properties of
      thalamic neurons have been shown. These studies suggest the important
      contribution of the thalamus in modulating pain in normal and neuropathic pain
      condition.

PMID- 22589601
TI  - Survival in Patients with Non-Small Cell Lung Cancer Who Opted out of Cancer
      Specific Therapy.
AB  - In Malaysia, many patients opted out of cancer-specific treatment for various
      reasons. This study was undertaken to investigate the survival rate of patients
      with stages I to III non-small cell lung cancer (NSCLC) who opted out of
      treatment, compared with those who accepted treatment. Case records of 119
      patients diagnosed with NSCLC between 1996 and 2003 in two urban-based hospitals
      were retrospectively examined. Survival status was ascertained from follow-up
      medical clinic records or telephone contact with patients or their next-of-kin.
      Median (25-75% IQR) survival rate for 79 patients who accepted and 22 patients
      who opted out of treatment, were 8.6 (16.0-3.7) and 2.2 (3.5-0.8) months
      respectively [log rank p< 0.001, Kaplan-Meier survival analysis]. Except for
      proportionately more patients with large cell carcinoma who declined treatment,
      there was no significant difference between the two groups in relation with age,
      gender, ethnicity, tumour stage, and time delays between symptom onset and
      treatment or decision-to-treat. We concluded that there was a small but
      significant survival benefit in accepting cancer-specific treatment. The findings
      imply that there is no effective alternative therapy to cancer-specific treatment
      in improving survival. However, overall prognosis for patients with NSCLC remains
      dismal.

PMID- 22589602
TI  - Impact of a spreading epidemic on medical students.
AB  - The emergence of severe acute respiratory syndrome (SARS) had caused fear and
      anxiety of unprecedented proportion. To examine the impact of SARS on the medical
      students in a private medical university, a self-reporting questionnaire study
      was carried out to assess the factual knowledge, anxiety level and perception of
      the crisis, among the students. The two-week study (between 12 and 23 May, 2003)
      was carried out three weeks after the first reported SARS-related death in
      Malaysia. Ninety-one Phase I (junior) and 113 Phase II (senior) students
      completed the questionnaires. A large majority of students of Phase I and II were
      correct in their factual knowledge and were sensible in their perception of the
      future and the handling of the crisis by government(s). However, phase 1 students
      expressed significantly greater degree of anxiety compared to Phase II in
      relation to attendance and personal protection in hospital, and in meeting people
      coughing in public places. The lesser degree of anxiety expressed by phase II
      senior students may be due in part, to a more realistic assessment of SARS risk
      brought about by maturity, time spent in hospital and interaction with clinical
      lecturers and medical staff.

PMID- 22589603
TI  - Insulin sensitivity and secretory status of a healthy malay population.
AB  - Insulin insensitivity is a common finding in several metabolic disorders
      including glucose intolerance, dyslipidemia, hyperuricemia and hypertension. Most
      of the previous studies on insulin sensitivity were performed on diabetic or
      obese population. So our knowledge about insulin sensitivity of healthy
      population remains limited. Rising prevalence of obesity, diabetes and metabolic
      syndrome is a serious issue in Malaysia and some other rapidly developing
      countries. So it is important to look at the insulin sensitivity status of
      healthy Malaysian subjects and to compare it in future with those of diabetic,
      obese or metabolic syndrome patients. In this study we sampled subjects who were
      independent of confounding factors such as obesity (including abdominal obesity),
      hypertension and glucose intolerance (diabetes, IGT or IFG) which may influence
      insulin sensitivity. Fasting plasma glucose, fasting insulin and lipid profile
      were determined. Insulin sensitivity and secretory status were calculated using
      the homeostasis model assessment (HOMA) software (HOMA%S, HOMA%B and HOMA-IR).
      The insulin sensitivity (HOMA%S) of healthy Malay subjects aged between 30-60
      years was 155.17%, HOMA-IR was 1.05 and HOMA%B was 116.65% (values adjusted for
      age, sex, BMI and waist circumference). It was seen that non-obese Malaysians can
      prevent age related lowering of insulin sensitivity if they can retain their BMI
      within limit.

PMID- 22589604
TI  - Rational management of differentiated thyroid cancer.
AB  - Differentiated thyroid cancer ( DTC ) is usually not very common ( incidence is
      about 1 % of all cancers and women are more often affected than men ). However,
      higher incidences has been reported in many parts of South East Asia particularly
      in iodine deficient areas. Unlike other solid tumors, DTC is potentially curable
      with documented survival rate of > 90 %. Even if the disease is not totally
      cured, through repeated high dose radio iodine therapy the progress of the
      disease can be controlled with significant improvement in quality of life for
      many years. This is possible if a proper and state of the art therapeutic
      approach is made. Since the incidence is relatively low, individual experience of
      treating physicians or centers is mostly inadequate leading to improper
      management with subsequent increase in morbidity and mortality. The purpose of
      this review is to evolve a rational management protocol for the treatment of
      thyroid cancer. Centers which do not have all facilities like high dose radio
      iodine therapy etc. may still follow the protocol by referring the patient for a
      particular step to another centre. What is needed is the awareness of the
      treating physician about the appropriate management of DTC. In recent years,
      there have been some important developments in the management of differentiated
      thyroid cancer like use of recombinant human thyrotropin (rhTSH), use of retinoic
      acid for redifferentiation etc. Some of these developments having practical
      relevance have been briefly mentioned.

PMID- 22589605
TI  - Is grandmultiparity a significant risk factor in this new millennium?
AB  - The aim of the study was to assess the outcomes of grandmultiparous women
      receiving the current obstetric care in Maternity Hospital Kuala Lumpur. Recent
      data regarding some of the complications are conflicting and the significance of
      grandmultiparity is now in question. Therefore, a retrospective cohort study of
      237 grandmultiparous and 254 multiparous women were undertaken. Chi-squared and t
      test were used (P<0.05) where appropriate. The results revealed that
      grandmultiparous women tend to be Malays, age above 35, have late antenatal
      booking and suffered from anemia and non-proteinuric hypertension. There was no
      significant difference in diabetes and glucose intolerance, ante partum and post
      partum hemorrhage. There was a significantly lower risk of first and second
      degree perineal tear, and prolonged first stage of labor. There was a significant
      increased in induction of labor but there was no uterine rupture and no increased
      in Cesarean Section. There was an increased in meconium stain liquor but there
      was no increased risk of fetal distress. The fetal outcome was good and there was
      no tendency to macrosomic infants or shoulder dystocia. With adequate care, the
      maternal fetal outcome of grandmutiparous women is good and comparable to the
      multiparous women. Anemia is still common and patient education is important to
      overcome this problem.

PMID- 22589606
TI  - Transnasal endoscopic repair for bilateral choanal atresia.
AB  - Choana atresia is a congenital abnormality of the posterior nasal apertures
      affecting the newborn. The aetiology is considered to be a persistence of the
      embroyological bucconasal membrane which separates the nasal cavity from the
      stomatodeum until it breaks down at seventh week, allowing communication through
      the primitive posterior nares. Bilateral choanal atresia almost always present as
      a respiratory emergency because newborn babies are obligate nasal breathers. The
      definitive surgical treatment is repair under general anaesthesia. We report our
      experience in doing a new technique of transnasal endoscopic repair.

PMID- 22589607
TI  - Typhoid and malaria co-infection - an interesting finding in the investigation of
      a tropical Fever.
AB  - Malaysia is endemic for both these diseases and one should not be too surprised
      when faced with a diagnosis of co-infection of typhoid and malaria, as have been
      described in India and Canada. Here we describe one such case of Salmonella typhi
      and Plasmodium vivax infection.

PMID- 22589608
TI  - Ensuring the standard of medical graduates in Malaysia.

PMID- 22589609
TI  - An overview of bone cells and their regulating factors of differentiation.
AB  - Bone is a specialised connective tissue and together with cartilage forms the
      strong and rigid endoskeleton. These tissues serve three main functions: scaffold
      for muscle attachment for locomotion, protection for vital organs and soft
      tissues and reservoir of ions for the entire organism especially calcium and
      phosphate. One of the most unique and important properties of bone is its ability
      to constantly undergo remodelling even after growth and modelling of the skeleton
      have been completed. Remodelling processes enable the bone to respond and adapt
      to changing functional situations. Bone is composed of various types of cells and
      collagenous extracellular organic matrix, which is predominantly type I collagen
      (85-95%) called osteoid that becomes mineralised by the deposition of calcium
      hydroxyapatite. The non-collagenous constituents are composed of proteins and
      proteoglycans, which are specific to bone and the dental hard connective tissues.
      Maintenance of appropriate bone mass depends upon the precise balance of bone
      formation and bone resorption which is facilitated by the ability of osteoblastic
      cells to regulate the rate of both differentiation and activity of osteoclasts as
      well as to form new bone. An overview of genetics and molecular mechanisms that
      involved in the differentiation of osteoblast and osteoclast is discussed.

PMID- 22589611
TI  - Histopathological studies of cardiac lesions after an acute high dose
      administration of methamphetamine.
AB  - Eighteen male Wistar rats aged six weeks were divided equally into
      Methamphetamine (MA), Placebo and Control group. MA group were injected with
      50mg/kg body weight of Methamphetamine hydrochloride (MAHCl) in normal saline,
      Placebo group were injected with normal saline only, while Control group not
      injected with anything. Five MA group rats died within four hours of injection
      and their hearts collected on the same day. Another MA group rat was sacrificed
      two days after injection. Placebo and control group were sacrificed at similar
      intervals. Collected hearts were studied for cardiac lesions under light
      microscopy using special staining and immunohistochemistry. Microscopic
      examination of the myocardium of the rats that died on the first day of injection
      showed loss of nuclei in some myocytes, indicating cell death. Some areas in the
      sub-endocardium region showed internalization and enlargement of myocyte nuclei,
      consistent with regeneration of cells. There were very few foci of necrosis
      observed in these samples. The heart samples from the single rat that survived
      injection for two days showed foci of infiltration of macrophage-like cells that
      were later revealed to be regenerating myocytes. There were also spindle-like
      fibroblasts, macrophages and a few leucocytes found within these foci. The
      overall appearance of the myocardium did not indicate any inflammatory response,
      and the expected signs of necrosis were not observed. These results suggest a
      need to re-evaluate the toxic and lethal dosages of MA for use in animals
      testing. Cause of death was suspected to be due to failure of other major organs
      from acute administration of MA. Death occurred within a time period where
      significant changes due to necrosis may not be evident in the myocardium. Further
      investigations of other organs are necessary to help detect death due to acute
      dosage of MA.

PMID- 22589610
TI  - Profound swim stress-induced analgesia with ketamine.
AB  - The potential of ketamine, an N-methyl D-aspartate (NMDA) receptor antagonist, in
      preventing central sensitization has led to numerous studies. Ketamine is
      increasingly used in the clinical setting to provide analgesia and prevent the
      development of central sensitization at subanaesthetic doses. However, few
      studies have looked into the potential of ketamine in combination with stress
      induced analgesia. This study looks at the effects of swim stress, which is
      mediated by opioid receptor, on ketamine analgesia using formalin test. Morphine
      is used as the standard analgesic for comparison. Adult male Sprague-Dawley rats
      were assigned to 6 groups: 3 groups (stressed groups) were given saline 1ml/kg
      intraperitoneally (ip), morphine 10mg/kg ip or ketamine 5mg/kg ip and subjected
      to swim stress; 3 more groups (non-stressed groups) were given the same drugs
      without swim stress. Formalin test, which involved formalin injection as the pain
      stimulus and the pain score recorded over time, was performed on all rats ten
      minutes after cessation of swimming or 30 minutes after injection of drugs.
      Combination of swim stress and ketamine resulted in complete analgesia in the
      formalin test which was significantly different from ketamine alone (p<0.05) and
      saline with stress (p<0.01). There is no significant difference between ketamine
      stressed and morphine stressed. These results indicate that ketamine and swim
      stress act synergistically to produce profound analgesia in the formalin test.
      This suggests that in the clinical setting, under stressful situations such as
      operative stress, ketamine is capable of producing profound analgesia at a
      subanaesthetic dose.

PMID- 22589613
TI  - An approach for assessment of tumor volume from mammography in locally advanced
      breast cancer.
AB  - Tumor size is an important independent indicator in patients with carcinoma of
      the breast. Repeated size measurements during primary systemic therapy produce
      detailed information about response that could be used to select the most
      effective treatment regimen and to estimate the patient's prognosis. Measurement
      of tumor burden with ultrasonography and computed tomography is being used with
      increasing frequency to assess the effectiveness of cytotoxic anticancer drugs.
      Standardization of assessment and results reporting are important steps that aim
      at increasing the amount of usable therapeutic information at the physician's
      disposal. The purpose of our study is to calculate the tumor volume by
      mammography after demagnification and compare the tumor volume measured from this
      method with ultrasonography volumes.

PMID- 22589612
TI  - Body composition and hand grip strength in male brick-field workers.
AB  - Ninety two male brickfield workers and sixty sedentary individuals of 25-45 years
      were randomly selected from brickfields of West Bengal, India, to evaluate the
      body composition and hand grip strength among male brickfield workers and to
      compare the data with their sedentary counterparts. Assessment of body
      composition by skinfold measurements and determination of hand grip strength
      (HGS) by hand grip dynamometer indicated significantly higher (p<0.001) fatness,
      skinfold values and body mass index (BMI) among the sedentary individuals though
      HGS and hand grip endurance were significantly higher (p<0.001) among brickfield
      workers. BMI and %fat values indicated that the subjects were non-obese and non
      overweight and regression norms for prediction of %fat from BMI in both the
      groups were computed as follows : Control Group : Y = 1.647 X - 22.789 (r = 0.92,
      p<0.001, SEE = 1.01), Brick-field Workers : Y = 0.747 X - 8.398 (r = 0.78,
      p<0.001, SEE = 1.34). Percentage of lean body mass (%LBM) was significantly
      higher (p<0.001) among brickfield workers whereas absolute LBM value had
      insignificant variation because of significant difference (p<0.001) in body mass
      between the groups. The present investigation revealed that the daily labour of
      the brick-field workers hindered the accumulation of body fat and extensive use
      of their hand and finger muscles enabled them to achieve greater arm strength.
      The proposed norms for prediction of %fat from BMI will also provide a first-hand
      impression about the body composition in the studied population.

PMID- 22589614
TI  - Laser posterior cordectomy for bilateral abductor vocal cord palsy : a case
      report.
AB  - Bilateral abductor vocal cord palsy is comparatively a rare vocal cord lesion,
      especially in a patient with no history of neck mass, previous surgery or trauma.
      Many patients are not stridulous. A patient presenting with stridor may need
      emergency airway management before the other treatment is commenced. We report a
      case of bilateral abductor palsy which required an emergency tracheostomy and
      subsequently a laser posterior cordectomy.

PMID- 22589615
TI  - A rare case of paediatric pontine glioblastoma presenting as a cerebellopontine
      angle otogenic abscess.
AB  - We describe rare case of a 9-year old boy who presented with a two-week history
      of right ear discharge and mild fever. Contrast enhanced CT scan of the brain
      showed a lesion in the right cerebellopontine angle with mild enhancement
      mimicking early abscess formation. Involvement of the mastoid air cells pointing
      towards a radiological diagnosis of mastoiditis reinforced the diagnosis of an
      abscess. A magnetic resonance imaging (MRI) was planned for the patient but his
      conscious level deteriorated and patient slipped into coma warranting immediate
      surgical intervention. Intraoperatively, about 90% of the tumour was removed and
      the appearance of the tumour resembled that of an acoustic schwannoma but
      histopathology confirmed the diagnosis of a glioblastoma multiforme (GBM). MRI
      done post operatively showed lesion in the pons confirming the diagnosis of an
      exophytic pontine glioblastoma multiforme.

PMID- 22589616
TI  - Cardiopulmonary resuscitation : the short comings in Malaysia.
AB  - This short review explores the current status of cardiopulmonary resuscitation in
      Malaysia and highlights some of the factors that have a negative impact on its
      rate of success. Absence of a unifying body such as a national resuscitation
      council results in non-uniformity in the practice and teaching of cardiopulmonary
      resuscitation. In the out-of-hospital setting, there is the lack of basic skills
      and knowledge in performing bystander cardiopulmonary resuscitation as well as
      using an automated external defibrillator among the Malaysian public. The
      ambulance response time is also a significant negative factor. In the in-hospital
      setting, often times, resuscitation is first attended by junior doctors or nurses
      lacking in the skill and experience needed. Resuscitation trolleys were often
      inadequately equipped.

PMID- 22589617
TI  - Why do we Need More Clinical Psychologists?

PMID- 22589619
TI  - Comparison Between Immunological Markers in Cord Blood of Preterm and Term Babies
      in Hospital USM.
AB  - A cross sectional pilot study using convenient sampling method was conducted to
      evaluate various immunological parameters in preterm babies and term babies. Cord
      blood from 36 preterm and 36 term babies was taken and the following parameters
      were determined: Immunoglobulin G, A and M, Complement 3 and 4 and NBT. The
      results showed that NBT was significantly reduced in preterm babies compared to
      term babies (7.5% versus 12.0%; p= 0.001). The complement levels, C3 (0.5114
      versus 0.7192 g/l; p<0.001) and C4 (0.07 versus 0.14g/l; p<0.001) were
      significantly lower in preterm babies than in the term babies. The mean IgG level
      in preterm babies was significantly lower than in term babies (9.5583 versus
      14.2806 g/l, p<0.001). IgM (0.1 versus 0.2g/l; p<0.001) and IgA (0.210 versus
      0.225g/l; p=0.036l) levels were significantly lower in the preterm than in term
      babies. In conclusion, we found that NBT reduction, IgG, IgA, IgM, C3 and C4
      levels were significantly lower in the preterm compared to term babies.

PMID- 22589620
TI  - Test anxiety: state, trait and relationship with exam satisfaction.
AB  - Test anxiety is defined as the reaction to stimuli that is associated with an
      individual's experience of testing or evaluating situations. This study aims to
      examine the fluctuation pattern of anxiety symptoms during a clinical examination
      and its relationship with underlying anxiety traits. Fourth year medical students
      of Penang Medical College undertaking the Ophthalmology clinical examination
      participated in this study. First phase of the survey, on anxiety symptoms was
      conducted immediately after the Ophthalmology clinical examination while the
      second phase, on pre-existing anxiety traits was conducted six weeks later with
      the aid of STAI instrument. Responses for both stages were combined and analyzed.
      Sixty-three of 122 students responded to both phases of the study, giving a
      response rate of 52%. All symptoms except trembling peaked 10 minutes before the
      exam begun showing a downward progression with no resurgence thereafter. Students
      with pre-existing anxiety traits had high anxiety scores 10 minutes into the
      examination and while with the examiners. Anticipatory anxiety is a source of
      concern and can effect performance and appropriate steps should be taken to help
      the students with this. A few other studies should be done to conclude.

PMID- 22589618
TI  - The Pharmacotherapy of Heparin-Induced Thrombocytopenia (HIT) : A Review of
      Contemporary Therapeutic Challenges in Clinical Practice.
AB  - Our objectives were to discuss a general overview on the description and
      recognition of heparin-induced thrombocytopenia (HIT) and present a critical
      review of the traditional and most recent advances in its pharmacotherapy.
      Computerized searches were done on MEDLINE and Iowa Drug Information Service
      (IDIS) databases from June 2001 until June 2007 and from May 2005 until May 2007,
      respectively. Search terms used included 'heparin-induced thrombocytopenia',
      'heparin-associated thrombocytopenia', therapeutics, HIT, HAT. We largely
      selected publications within the timeframe above, but did not exclude commonly
      referenced and highly regarded older publications. The commonly referenced
      published articles were obtained through manual searches derived from
      bibliographic citations and retrievals from the authors' personal files.
      Pertinent literatures (89 key articles) that were thought to have substantially
      contributed new information to the therapeutics of HIT within the last 6 years
      were identified, reviewed and presented. The following limits were used for the
      MEDLINE and IDIS searches: 'human', drug therapy', 'review', 'meta-analysis',
      'clinical trial', and case reports. The therapeutics of HIT is rapidly evolving
      and needs to consider an evidence - based approach. It is imperative that
      practitioners be aware of the associated risk and be up-to-date with the current
      advances in the management of this fatal clinical condition.

PMID- 22589621
TI  - The prevalence of bronchopulmonary infection among patients with rheumatoid
      arthritis versus non rheumatoid arthritis patients.
AB  - A high frequency of bronchopulmonary infections complicating rheumatoid arthritis
      has been described in reports of case series. This study was undertaken to
      confirm and compare these finding in patients with RA and control. 117 patients
      with RA and 103 patients with OA/soft tissue rheumatism as controls. Study
      subjects were studied using their medical records available from hospitals'
      casenotes and GP data base. Details of all documented bronchopulmonary infections
      for the preceding year including lower and upper respiratory tract infections
      were recorded. Details of hospital admissions due to bronchopulmonary infection,
      antibiotic usage and functional capacity were also recorded. Mean age for RA was
      56 and 59 for control. There were 34 males and 83 females in RA group, however,
      14 males and 55 females in control group. There were at least 1 episodes of BPI
      in 66.7% (p<0.05) patients with RA and 48.5% in control. 69.2% (p<0.05) of
      subgroup patients with RA were noted to have poorer functional capacity compared
      to 50% in control. More RA patients with BPI (15%) (p<0.05) were admitted to
      hospital compared to control (3.8%). Significance findings were noted in terms of
      prevalence of BPI in RA patients compared to controls as well as patients with RA
      have severe course of BPI warranting hospitalization. RA patients with poorer
      functional capacity also noted to have high incidence of BPI.

PMID- 22589622
TI  - Outcome of Laser-Assisted Uvulopalatoplasty (LAUP) in the Management of Snoring
      in Hospital Universiti Sains Malaysia (USM).
AB  - To determine the outcome of laser-assisted uvulopalatoplasty for the management
      of patients with snoring in Universiti Sains Malaysia Hospital (HUSM). A
      retrospective review of patients who underwent LAUP with or without tonsillectomy
      or adenoidectomy under general anaesthesia between December 2003 to December
      2006. Data was obtained from admission and follow-up records in the
      otorhinolaryngology clinic of USM Hospital (HUSM). A total of nineteen patients
      underwent procedure for the treatment of snoring. Majority of these patients
      presented with symptoms of loud snoring and daytime somnolence. The main
      operations performed were LAUP with or without tonsillectomy or adenoidectomy.
      The justification for LAUP were overhanging and excessive uvula or soft palate,
      whereas for adenotonsillectomy were the hypertrophied adenoids and tonsils. On
      follow-up, most of the patients claimed improvement of snoring within the first 2
      months post-operation. However, majority of them defaulted follow-up after that.
      One patient (AHI preoperatively was mild) was reviewed up to 8 months with no
      snoring. One patient (AHI was severe preoperatively and normal post operatively)
      remained in our follow-up was satisfied with the operation. Two patients
      continued to experience snoring post LAUP despite trial of non-surgical methods.
      The outcome of LAUP in our patients showed variable results. This showed that
      patient selection is very important to achieve good result in LAUP. Long-term
      follow-up is also essential to document the success for LAUP.

PMID- 22589623
TI  - Evaluation of a training programme for non-health professionals as oral health
      educators.
AB  - Involvement of oral health educators among non-health professionals in oral
      health promotion is important in the prevention of oral diseases. This study was
      carried out to compare the level of oral health knowledge among pre-school
      teachers before and after oral health seminar. Pre-test data was collected by
      distributing questionnaire to pre-school teachers in Pasir Mas, who attended the
      seminar on "Oral Health" (n=33) and they were required to fill anonymously before
      the seminar started. The questions consisted of information on general
      background, perceived oral health status, oral health knowledge and the
      environment where they work. After two weeks, post-test data was collected using
      the same structured questionnaire and identification code was used to match the
      pre and post data. SPSS 11.5 was use for statistical analysis. Two out of 33
      eligible preschool teachers were considered non-respondents due to absenteeism
      during the post-test data collection. The response rate was 94.0% (n = 31). The
      study shows a significant improvement in oral health knowledge among pre-school
      teachers in Pasir Mas, after seminar (p < 0.001) as compared to controls. Thus,
      we can conclude that the oral health programme (seminar) appeared effective at
      influencing oral health educator's knowledge towards oral health.

PMID- 22589624
TI  - The Serum Levels of Trace Metals in Nigerian Males with Different PSA Values.
AB  - Prostate cancer (PCa), the primary disease of men over 50 years of age is on the
      increase worldwide. Most PCa grows slowly from overt clinical disease to the
      stage that lead to death. The gradual course of PCA development provides
      opportunity for intervention. Supplement of diet taken by PCa patients may be an
      effective intervention because certain micronutrients had been implicated in
      cancer prevention. The present study is designed to determine the levels of trace
      metals in 80 Nigeria males having different concentrations of serum prostate
      surface antigen (PSA) using atomic absorption spectrophotometer. The serum levels
      of PSA were measured with Beckman Coulter Access Immunoassay automated machine.
      Subjects with PSA values 5-10ng/ml had significantly high serum levels of Zn, Fe,
      Cd and Mn but significantly low level of Se compared with the controls (PSA 0
      4ng/ml). Subjects with PSA >10ng/ml had significantly low levels of Mn, Mg and Se
      compared with the controls. Subjects with PSA values 5-10ng/ml had significantly
      reduced level of Se compared with subjects with PSA >10ng/ml. Only Se was low in
      all subjects with PSA >4ng/ml, therefore there is a possibility that Se intake
      may reduce the risk and progression of PCA.

PMID- 22589625
TI  - Molecular genetic analysis of a suprasellar immature teratoma : mutation of exon
      4 p53 gene.
AB  - We described an intracranial immature teratoma in a 13 year old Malay boy who
      presented with history of chronic headache and blurring of vision. Physical
      findings revealed bilateral papilloedema but no other localizing sign. A Magnetic
      Resonance Imaging of the brain revealed a suprasellar well defined lobulated
      midline heterogenous mass which was intraoperatively described as mainly solid
      tumour with multiple small cystic component filled with yellowish jelly like
      material. Histopathological finding confirmed the case as immature teratoma.
      Molecular genetic analysis of p53 and p27 genes revealed substitution of
      nucleotide G to C at location nucleotide 12139, exon 4 of gene p53. No alteration
      was detected at exon 5-6 and 8 of p53 gene and exon 1 and 2 of p27 gene. This is
      the first case report of an intracranial immature teratoma with genetic mutation
      occuring in a Malay boy.

PMID- 22589626
TI  - Health major incident : the experiences of mobile medical team during major
      flood.
AB  - Disaster is a sudden event that associated with ecological changes, disruption of
      normal daily activities, destruction of infrastructures, loss of properties, and
      medical disabilities. In disaster, there is a mismatch between available
      resources and patients need for healthcare service. During flood disaster, the
      victims were predisposed to different type of illnesses for various reasons such
      as inadequate supply of clean water, poor sanitation or drainage system,
      unhealthy foods, and over-crowded relief centers. Mobile clinic is an option for
      delivering medical care for the disaster victims who often have a difficulty to
      access to the medical facilities. In this article we would like to share our
      experiences during the provision of humanitarian services for flood victims at
      District of Muar Johor. Common illnesses among the flood victims at visited
      relief centers and advantages of Mobile Medical Relief Team were also highlighted
      and discussed.

PMID- 22589627
TI  - Words from the current editor of MJMS.

PMID- 22589628
TI  - Why diagnosa was started.

PMID- 22589629
TI  - Beginning of scientific publications in school of medical sciences, universiti
      sains malaysia.

PMID- 22589630
TI  - A herculean task for MJMS.

PMID- 22589631
TI  - MJMS : the past and future.

PMID- 22589632
TI  - MJMS and the challenges of a research university.

PMID- 22589633
TI  - Life event, stress and illness.
AB  - The relationship between stress and illness is complex. The susceptibility to
      stress varies from person to person. Among the factors that influenced the
      susceptibility to stress are genetic vulnerability, coping style, type of
      personality and social support. Not all stress has negative effect. Studies have
      shown that short-term stress boosted the immune system, but chronic stress has a
      significant effect on the immune system that ultimately manifest an illness. It
      raises catecholamine and suppressor T cells levels, which suppress the immune
      system. This suppression, in turn raises the risk of viral infection. Stress also
      leads to the release of histamine, which can trigger severe broncho-constriction
      in asthmatics. Stress increases the risk for diabetes mellitus, especially in
      overweight individuals, since psychological stress alters insulin needs. Stress
      also alters the acid concentration in the stomach, which can lead to peptic
      ulcers, stress ulcers or ulcerative colitis. Chronic stress can also lead to
      plaque buildup in the arteries (atherosclerosis), especially if combined with a
      high-fat diet and sedentary living. The correlation between stressful life events
      and psychiatric illness is stronger than the correlation with medical or physical
      illness. The relationship of stress with psychiatric illness is strongest in
      neuroses, which is followed by depression and schizophrenia. There is no
      scientific evidence of a direct cause-and-effect relationship between the immune
      system changes and the development of cancer. However, recent studies found a
      link between stress, tumour development and suppression of natural killer (NK)
      cells, which is actively involved in preventing metastasis and destroying small
      metastases.

PMID- 22589634
TI  - Correlations between subdural empyema and paraclinical as well as clinical
      parameters amongst urban malay paediatric patients.
AB  - Paediatric subdural empyema is frequently seen in developing Asean countries
      secondary to rinosinusogenic origins. A cross-sectional analysis on the surgical
      treatment of intracranial subdural empyema in Hospital Kuala Lumpur (HKL), a
      major referral center, was done in 2004. A total number of 44 children who
      fulfilled the inclusion criteria were included into this study. The methods of
      first surgery, volume of empyema on contrasted CT brain, improvement of
      neurological status, re-surgery, mortality and morbidity, as well as the
      demographic data such as age, gender, sex, duration of illness, clinical
      presentation, probable origin of empyema, cultures and follow-up were studied.
      Chi-square test was performed to determine the association between surgical
      methods and the survival of the patients, neurological improvement, clearance of
      empyema on CT brain, re-surgery and long morbidity among the survivors. If the
      20% or more of the cells were having expected frequency less than five, then
      Fisher's Exact test was applied. The level of significance was set at 0.05. SPSS
      version 12.0 was used for data entry and data analysis. There were 44 patients
      who were less than 18 years. Their mean age was 5.90 +/- 6.01 years. There were
      30 males (68.2%) and 14 females (31.8%) involved in the study. Malays were
      majority with 28 (63.6%) followed by Indian 8 (18.2%), Chinese 5 (11.4%) and
      others 3 (6.8%). The variables which were under interest were gender, race,
      headache, vomiting, seizures, sign of meningism, cranial nerve palsy, thickness
      site of abscess, first surgical treatment, improvement in neurological deficit,
      clearance of CT and whether re-surgery was necessary. All variables were found
      not to be associated with Henk W Mauser Score for PISDE grading. Comparison
      between this urban study and a rural setting study by the same corresponding
      author in the same period on subdural empyema was done. Common parameters were
      compared and it was found out that seizures were more prevalent in urban study
      where the patients are more than one year old (p=0.005). Mortality was much
      higher in urban study than the rural one (p=0.040). The larger proportion of
      urban group had volume of abscess less than or equal to 50 ml (p=< 0.001).

PMID- 22589635
TI  - Knowledge, attitude and practice of sawmill workers towards noise-induced hearing
      loss in kota bharu, kelantan.
AB  - The purpose of this study was to determine the sawmill workers' knowledge,
      attitude and practice (KAP) in relation to noise-induced hearing loss (NIHL). A
      cross-sectional study was conducted involving 83 workers from 3 factories in Kota
      Bharu, Kelantan. Questionnaires were distributed to obtain the socio-demography,
      knowledge, attitude and practice level in relation to noise-induced hearing loss
      (NIHL). The weak areas identified in the knowledge section were treatment aspects
      (15.5%), signs and symptoms of NIHL (20.2%) and risk factors (31%). As for
      attitude; the prevention aspects were the lowest (25.3%), followed by risk taking
      attitude (26.2%), and causes of hearing loss (42.1%). Overall, the practice was
      not encouraging at all. It is important to have an education program to raise
      workers' awareness and to improve their attitude and practices towards noise
      induced hearing loss.

PMID- 22589636
TI  - Tooth wear prevalence and sample size determination : a pilot study.
AB  - Tooth wear is the non-carious loss of tooth tissue, which results from three
      processes namely attrition, erosion and abrasion. These can occur in isolation or
      simultaneously. Very mild tooth wear is a physiological effect of aging. This
      study aims to estimate the prevalence of tooth wear among 16-year old Malay
      school children and determine a feasible sample size for further study. Fifty
      five subjects were examined clinically, followed by the completion of self
      administered questionnaires. Questionnaires consisted of socio-demographic and
      associated variables for tooth wear obtained from the literature. The Smith and
      Knight tooth wear index was used to chart tooth wear. Other oral findings were
      recorded using the WHO criteria. A software programme was used to determine
      pathological tooth wear. About equal ratio of male to female were involved. It
      was found that 18.2% of subjects have no tooth wear, 63.6% had very mild tooth
      wear, 10.9% mild tooth wear, 5.5% moderate tooth wear and 1.8 % severe tooth
      wear. In conclusion 18.2% of subjects were deemed to have pathological tooth wear
      (mild, moderate & severe). Exploration with all associated variables gave a
      sample size ranging from 560 - 1715. The final sample size for further study
      greatly depends on available time and resources.

PMID- 22589637
TI  - Evaluation of the management of sexually transmitted infections by private
      practitioners in pulau pinang, malaysia.
AB  - To determine the current practices of private practitioners for the management of
      STIs in Pulau Pinang, Malaysia, evaluation of pharmacotherapy for STIs in private
      clinics and to ascertain the management of STIs compared to standard guidelines.
      METHODS: Data was collected by self-administered questionnaire for private
      practitioners, which gathered information on their socio-demographic as well as
      practice characteristics. Descriptive statistical analysis was performed by using
      SPSS for Windows version 13.0. RESULTS: Data was collected from 78 practitioners.
      Most of the treatment choices mentioned for the treatment of gonorrhea were
      inconsistent with the guidelines. About 51.2% of practitioners did not screen
      their patients for HIV/AIDS. Majority of private practitioners counseled their
      patients about HIV/AIDS on an irregular basis. A high percentage of 59% did not
      inform health authorities about STI cases and 32.1% mentioned that they did not
      use any guidelines. CONCLUSIONS: Management of STIs by private practitioners with
      respect to selection of antibiotics, patient counseling and case notification
      leaves a lot to be desired. Current management practices can adversely impact on
      HIV/AIDS transmission in the country. Interventions are needed to improve the
      management practices of private practitioners.

PMID- 22589638
TI  - Functional outcome at 6 months in surgical treatment of spontaneous
      supratentorial intracerebral haemorrhage.
AB  - A prospective cohort study was done to evaluate the role of surgery in patients
      with spontaneous supratentorial intracerebral haemorrhage (SICH) and to identify
      predictors of outcome including the use of invasive regional cortical cerebral
      blood flow (rCoBF) and microdialysis. Surgery consisted of craniotomy or
      decompressive craniectomy. The ventriculostomy for intracranial pressure (ICP)
      monitoring and drainage and regional cortical cerebral blood flow (rCoBF) and
      microdialysis were performed in all subjects. Pre and post operative information
      on subjects were collected. The study end points was functional outcome at 6
      months based on a dichotomised Glasgow Outcome Scale (GOS).The selected clinical,
      radiological, biochemical and treatment factors that may influence the functional
      outcome were analysed for their significance. A total of 36 patients were
      recruited with 27(75%) patients had Glasgow Coma Score (GCS) between 5 to 8 on
      admission and 9(25%) were admitted with GCS of 9. At 6 months, 86 % had a poor or
      unfavourable outcome (GOS I-III) and 14% had good or favourable outcome (GOS IV
      V). The mortality rate at 6 months was 55%. Univariate analysis for the
      functional outcome identified 2 significant variables, the midline shift
      (p=0.013) and mean lactate:pyruvate ratio (p=0.038). Multivariate analysis
      identified midline shift as the single significant independent predictor of
      functional outcome (p=0.013).Despite aggressive regional cortical cerebral blood
      flow (rCoBF) and microdialysis study for detection of early ischemia, surgical
      treatment for spontaneous intracerebral haemorrhage only benefited a small number
      of patients in terms of favourable outcome (14%) and in the majority of patients
      (86%), the outcome was unfavourable. Patients with midline shift > 5mm has almost
      21 times higher chances (adj) OR 20.8 of being associated with poor outcome (GOS
      I-III).

PMID- 22589639
TI  - Delayed traumatic intracranial haemorrhage and progressive traumatic brain injury
      in a major referral centre based in a developing country.
AB  - A repeat Computer Tomographic (CT) brain after 24-48 hours from the 1(st)
      scanning is usually practiced in most hospitals in South East Asia where
      intracranial pressure monitoring (ICP) is routinely not done. This interval for
      repeat CT would be shortened if there was a deterioration in Glasgow Coma Scale
      (GCS). Most of the time the prognosis of any intervention may be too late
      especially in hospitals with high patient-to-doctor ratio causing high mortality
      and morbidity. The purpose of this study was to determine the important
      predictors for early detection of Delayed Traumatic Intracranial Haemorrhage
      (DTICH) and Progressive Traumatic Brain Injury (PTBI) before deterioration of GCS
      occurred, as well as the most ideal timing of repeated CT brain for patients
      admitted in Malaysian hospitals. A total of 81 patients were included in this
      study over a period of six months. The CT scan brain was studied by comparing the
      first and second CT brain to diagnose the presence of DTICH/PTBI. The predictors
      tested were categorised into patient factors, CT brain findings and laboratory
      investigations. The mean age was 33.1 +/- 15.7 years with a male preponderance of
      6.36:1. Among them, 81.5% were patients from road traffic accidents with Glasgow
      Coma Scale ranging from 4 - 15 (median of 12) upon admission. The mean time
      interval delay between trauma and first CT brain was 179.8 +/- 121.3 minutes for
      the PTBI group. The DTICH group, 9.9% of the patients were found to have new
      intracranial clots. Significant predictors detected were different referral
      hospitals (p=0.02), total GCS status (p=0.026), motor component of GCS (p=0.043),
      haemoglobin level (p<0.001), platelet count (p=0.011) and time interval between
      trauma and first CT brain (p=0.022). In the PTBI group, 42.0% of the patients
      were found to have new changes (new clot occurrence, old clot expansion and
      oedema) in the repeat CT brain. Univariate statistical analysis revealed that age
      (p=0.03), race (p=0.035), types of admission (p=0.024), GCS status (p=0.02),
      pupillary changes (p=0.014), number of intracranial lesion (p=0.004), haemoglobin
      level (p=0.038), prothrombin time (p=0.016) as the best predictors of early
      detection of changes. Multiple logistics regression analysis indicated that age,
      severity, GCS status (motor component) and GCS during admission were
      significantly associated with second CT scan with changes. This study showed that
      9.9% of the total patients seen in the period of study had DTICH and 42% had
      PTBI. In the early period after traumatic head injury, the initial CT brain did
      not reveal the full extent of haemorrhagic injury and associated cerebral oedema.
      Different referral hospitals of different trauma level, GCS status, motor
      component of the GCS, haemoglobin level, platelet count and time interval between
      trauma and the first CT brain were the significant predictors for DTICH. Whereas
      the key determinants of PTBI were age, race, types of admission, GCS status,
      pupillary changes, number of intracranial bleed, haemoglobin level, prothrombin
      time and of course time interval between trauma and first CT brain. Any patients
      who had traumatic head injury in hospitals with no protocol of repeat CT scan or
      intracranial pressure monitoring especially in developing countries are advised
      to have to repeat CT brain at the appropriate quickest time .

PMID- 22589640
TI  - Stomach gastrointestinal stromal tumours (GIST) intussuscepted into duodenum : a
      case report.
AB  - Gastrointestinal stromal tumours (GIST) are tumours of gastrointestinal tract and
      mesentery. The commonest site of its occurrence is the stomach. Patients with
      GIST are usually asymptomatic but they can present as abdominal pain, bleeding
      and rarely gastric outlet obstruction. In this particular case, the patient
      presents with symptoms of anaemia, partial gastric outlet obstruction and
      intermittent epigastric pain. Laparotomy was performed and a diagnosis of
      gastroduodenal intussusception secondary to gastrointestinal stromal tumour was
      made.

PMID- 22589642
TI  - USM Apex University Status: Transforming Higher Education For A Sustainable
      Tomorrow.
AB  - This special editorial for the month of January 2009 is "THE" interview with
      Professor Tan Sri Dato' Dzulkifli Abdul Razak, Vice Chancellor of the Universiti
      Sains Malaysia (USM). He talked to us about the Apex University status that was
      conferred on 3rd September 2008. While most newspapers and the rest of the media
      were in frenzy interviewing him that month, MJMS decided to catch up with him on
      Monday 15th December 2008 just before the celebration at the Dewan Utama,
      Universiti Sains Malaysia Health Sciences Campus to commemorate the 25th
      anniversary of the establishment of the Hospital University Sains Malaysia by
      Yang Berhormat, Minister of Higher Education Datuk Seri Mohamed Khaled Nordin.
      References to USM as an APEX University are included at the end of this editorial
      especially for non-USM readers.

PMID- 22589643
TI  - Pre-eclampsia: is it all in the placenta?
AB  - Hypertensive disorders of pregnancy complicate almost 7 - 10 % of all
      pregnancies. The dyad of hypertension and proteinuria after 20 weeks of gestation
      is referred to as pre-eclampsia. It is a major cause of maternal morbidity and
      mortality and is also associated with increased perinatal problems. Despite
      intensive research over the years the exact cause of pre-eclampsia remains
      unknown. Nevertheless, information gleaned from published studies point to the
      placenta as the probable pathogenetic focus of pre-eclampsia, as the disease
      usually resolves within 24 - 48 hours after delivery of the placenta. Although
      the precise involvement of the placenta in pre-eclampsia remains unclear there
      are indications that the trophoblastic invasion of the uterine spiral arteries is
      abnormal in women who develop pre-eclampsia. This impaired invasion leads to
      decreased placental perfusion and ultimately to placental hypoxia. The distressed
      or ischaemic placenta then secretes a factor(s) into the maternal circulation,
      which cause/s widespread endothelial cell dysfunction characterized by vasospasm,
      activation of coagulation system and organ ischaemia. The cause of the defective
      cytotrophoblastic invasion of the spiral arteries and the link between placental
      ischaemia and generalized maternal endothelial dysfunction remain unknown.
      Although the placenta appears to have a major role in the pathogenesis of pre
      eclampsia, evidence also suggests that factors like maternal genetic
      predisposition, dietary, environmental and behaviour, which surface during the
      stress of pregnancy might also be involved in the development of pre-eclampsia.
      It is known that not all women with poor cytotrophoblast invasion develop pre
      eclampsia and not all women with preeclampsia show poor cytotrophoblast invasion.
      Over the years, a number of potential risk factors associated with the
      development of pre-eclampsia are being recognized and it might be appropriate now
      to develop some preventative strategies based upon the available information.

PMID- 22589644
TI  - Hospital Universiti Sains Malaysia (HUSM): 25 Years Of Excellent Service.
AB  - Our Hospital University Sains Malaysia (HUSM) was given the Cabinet approval to
      exist under the Ministry of Education on 23 November 1982. The Deputy Prime
      Minister during that period, Yang Berhormat Tun Musa Hitam announced this after
      the cabinet meeting was held together with the presence of the Yang Berhormat
      Ministers of Health; and Education, Director of the Public Works Department and
      the Implementation and Coordinating Unit, Prime Minister's Department. The first
      patients moved in on 14 March 1983 and the inauguration of HUSM was done on 26
      August 1984 by the Duli Yang Maha Mulia Tuanku Ismail Petra Ibni Al-Marhum Sultan
      Yahya Petra, the Sultan of Kelantan Darul Naim. HUSM celebrated it's 25th
      anniversary at the Dewan Utama, USM Health Campus on the 15th December 2008 which
      was inaugurated by Yang Berhormat, Minister of Higher Education Dato' Seri
      Mohamed Khaled Nordin. USM's Vice Chancellor Professor Tan Sri Dato' Dzulkifli
      Abdul Razak, Chairman of the USM Board of Directors Tan Sri Dato' Haji Dr. Ani
      bin Arope, Health Campus Director Professor Dato' Dr. Mafauzy Mohamed, former
      Campus Director, Dato' Prof Mohd Roslani Abdul Majid, the current and previous
      Hospital Directors and Deputy Directors since 1983 were present. The achievements
      of HUSM since its establishment and its vision to fulfil the University's
      Accelerated Programme for Excellence (APEX) are elaborated.

PMID- 22589645
TI  - Radioiodine I-131 for the therapy of graves' disease.
AB  - Graves' disease is a common cause of hyperthyroidism. Treatment options for
      Graves' disease include antithyroid medication, surgery or radioactive iodine (I
      31) or RAI. This review will focus on the approach to RAI therapy; discussing
      dose selection, patient preparation, and consideration before and after
      administering RAI, examining aspects of pre-treatment with antithyroid medication
      as well as discussing possible adverse events including hypothyroidism and
      possible worsening of thyroid-associated opthalmopathy. Follow-up is lifelong
      with the aim of ensuring the patient remains euthyroid or on replacement therapy
      if there is evidence of hypothyroidism. While there are controversies in
      treatment of thyrotoxicosis with RAI, with appropriate patient selection and
      regular follow-up, radioiodine is a safe and effective modality in achieving high
      cure rates.

PMID- 22589647
TI  - Neuropsychological assessment in epilepsy surgery - preliminary experience in a
      rural tertiary care hospital in north East malaysia.
AB  - We present our preliminary experience in neuropsychological testing in epilepsy
      surgery patients to demonstrate how these tests contributed to decide the
      laterality of epileptic focus, and to assess the effect of surgery on patient's
      cognitive function and quality of life. Preoperative neuropsychological tests
      consisting of Wechsler Adult Intelligence Scale-III (WAIS) for IQ, Wechsler
      Memory Scale-III (WMS) for memory and patients' quality of life (QOLIE 31) were
      administered to refractory epilepsy patients under evaluation for surgical
      treatment. These tests were repeated one year after surgery and we studied any
      changes in trends. A total of seven patients were recruited in this study between
      July 2004 and July 2006. The aetiologies of refractory epilepsy were pure mesial
      temporal sclerosis (MTS) in five patients, dysembryogenic neuroepithelial tumour
      (DNET) in one and dual lesion of cavernous angioma with ipsilateral MTS in one.
      The preoperative neuropsychological tests were all in concordance to MRI finding,
      and showed good contralateral function; five lateralises to the right and two to
      the left. The post-operative Engel seizure count (median 8.00, IQR 7.00-8.75),
      general IQ (88 vs. 79), performance IQ (94 vs. 79), verbal memory (89 vs. 71),
      non-verbal memory (88 vs. 75) and QOLIE (53.14 vs. 44.71) were better compared to
      preoperative values. The verbal IQ (84 vs. 84) was unchanged. Neuropsychological
      tests are useful as ancillary investigations to determine the laterality of
      seizure focus and integrity of function in the contralateral temporal lobe.
      Following successful surgical treatment, there is a trend towards improvement in
      memory, IQ and quality of life scores in this small group of patients.

PMID- 22589646
TI  - Labour induction with randomized comparison of oral and intravaginal misoprostol
      in post date multigravida women.
AB  - The efficacy and safety of oral versus vaginal misoprostol for elective induction
      of labor in post date multigravida with an unfavourable cervix was compared over
      a period of one year in the Bahawal Victoria Hospital, Bahawalpur, Pakistan.
      Eightyeight multigravida post date women were divided into two groups and given
      50 mg misoprostol orally and 50 mg intravaginally, respectively. The induction to
      onset of significant uterine contractions and delivery intervals were lower in
      the first group (7.8 h vs. 8.9 h) when compared to (10.4 h vs. 12 h). The first
      group had a higher rate of Caesarean section (7% vs. 4%; p>0.05), uterine
      hyperstimulation (9% vs. 5%; p>0.05), uterine tachysystole (23% vs. 14%; p>0.05)
      and neonatal admissions to intensive care unit (12% vs. 4%; p>0.05) when compared
      to second group. Fifty mg oral misoprostol has the potential to induce labor as
      safely and effectively as the intravaginal route.

PMID- 22589648
TI  - A pilot study on percent free prostate specific antigen as an additional tool in
      prostate cancer screening.
AB  - A cross sectional pilot study was carried out to look into the usefulness of
      percent free prostate specific antigen (fPSA) in the diagnosis of prostatic
      cancer in HUSM patients. All patients who attended surgical clinic and admitted
      to surgical wards with signs and symptoms of prostate problems during the study
      period were taken as the study subjects. Total prostate specific antigen (tPSA)
      was estimated by immunoassay technique and those values of 4 ng/mL or more were
      proceeded for estimation of fPSA. Using the cut-off value of less than 25% fPSA
      for diagnosing patients with prostate cancer, our study showed that majority of
      the prostate cancer patients have a ratio of fPSA:tPSA more than 25% and a
      significantly higher level of total prostate specific antigen (P<0.005) when
      compared with patients with benign prostatic hyperplasia (BPH). Unexpectedly, the
      fPSA values were high in patients diagnosed as prostate cancer compared to BPH.
      Ratio of percent fPSA to tPSA was found not to be sensitive and specific, in
      diagnosing prostate cancer at the cut-off value of 25%. In conclusion, total PSA
      is a more useful biochemical test for diagnosing prostate cancer in our patients.

PMID- 22589649
TI  - A gluteal mass of langerhans cell histiocytosis mimicking malignancy in a two
      year-old boy: a case report.
AB  - Langerhans cell histiocytosis is a disease primarily affects the bone. More than
      50 percent of the disease occurs between the age of 1 and 15. We reported a case
      of a 2 year old boy who presented with a gluteal mass. Radiographic imaging
      showed an osteolytic lesion suspicious of malignancy. However, the histological
      diagnosis was Langerhans cell histiocytosis.

PMID- 22589650
TI  - Neurological rehabilitation of stroke patients by means of a robotically assisted
      brain controlled interface.

PMID- 22589651
TI  - Cytogenetics: past, present and future.
AB  - Fifty years have elapsed since the discovery of the number of human chromosomes
      in 1956. Newer techniques have been developed since then, ranging from the
      initial conventional banding techniques to the currently used molecular array
      comparative genomic hybridisation. With a combination of these conventional and
      molecular techniques, cytogenetics has become an indispensable tool for the
      diagnosis of various genetic disorders, paving the way for possible treatment and
      management. This paper traces the history and evolution of cytogenetics leading
      up to the current state of technology.

PMID- 22589652
TI  - The role of cells, neurotrophins, extracellular matrix and cell surface molecules
      in peripheral nerve regeneration.
AB  - Wallerian degeneration is a complicated process whereby axons and myelin sheaths
      undergo degeneration, and eventually are phagocytosed by macrophages and Schwann
      cells following nerve damage. Schwann cells proliferate and the endoneural tubes
      persist. In addition, neurotrophins, neural cell adhesion molecules, cytokines
      and other soluble factors are upregulated to facilitate regeneration. The
      important role of cellular components, neurotrophins, and extracellular matrix
      components, including cell surface molecules involved in this regenerative
      process, is highlighted and discussed in this review.

PMID- 22589653
TI  - Attenuation of hydrogen peroxide and ferric reducing/antioxidant power serum
      levels in colorectal cancer patients with intestinal parasitic infection.
AB  - BACKGROUND: This study assessed several common oxidative indices in subjects
      infected with intestinal parasites, as well as in colorectal cancer (CRC)
      patients both with and without intestinal parasites. METHOD: Serum levels of
      malondialdehyde (MDA), ferric reducing/antioxidant power (FRAP), and hydrogen
      peroxide (H(2)O(2)) were measured, as were plasma levels of advanced oxidation
      protein products (AOPP), all according to established methods. The presence of
      intestinal parasites was confirmed by stool examination. RESULTS: All intestinal
      parasiteinfected subjects and CRC patients showed the presence of oxidative
      stress. Thirtysix percent of the CRC patients had intestinal parasitic
      infections. The levels of H(2)O(2) and FRAP in parasite-infected subjects were
      significantly higher than in CRC patients, but these levels were significantly
      lower in the CRC patients with parasitic infections. CONCLUSION: Parasitic
      infection and CRC may contribute to oxidative stress independently, but when
      present together, the oxidative stress burden imposed by parasites may be
      attenuated.

PMID- 22589654
TI  - Body mass index and body fat status of men involved in sports, exercise, and
      sedentary activites.
AB  - A cross-sectional study was carried out in Kota Bharu on three groups of men with
      ages ranging from 18 to 44 years. The study groups included 83 athletes
      representing various types of sports and levels of participation (athlete group),
      80 active men who exercised a minimum of 30 minutes per day at least 3 times per
      week (exercise group), and 80 inactive men (sedentary group). The objectives of
      the study were to compare the body mass indices (BMIs) and body fat statuses
      among the three groups with different physical activity levels. The height and
      weight of respondents were measured using the Seca weighing balance with height
      attachment. Skinfold thickness of biceps, triceps, subscapular regions, and
      suprailiac regions of each respondent were measured using Harpenden skinfold
      calipers. Percentage body fat was calculated as the sum of the four measurements
      of skinfold thickness. The results showed that the mean (+/- SD) BMIs in the
      athlete, exercise, and sedentary groups were 22.6 +/- 2.9, 23.4 +/- 3.5, and 24.3
      +/- 4.6 kg/m(2), respectively. The combined prevalence of pre-obese (BMI
      25.029.9) and obese (BMI 3 30.0) subjects was 21.7% in the athlete group, 29.9%
      in the exercise group, and 47.5% in the sedentary group. The mean (+/- SD)
      percentage of body fat in athletes was 15.7 +/- 5.4%, which was lower than in the
      exercise (18.9 +/- 5.5%) and sedentary (20.6 +/- 5.8%) groups. The study revealed
      that individuals who are actively involved in physical activity, particularly in
      sport activities, have lower BMIs and percentage body fat values compared to
      sedentary people. Therefore, to prevent obesity, all individuals are encouraged
      to perform regular physical activity, particularly sports activities.

PMID- 22589655
TI  - Antimicrobial susceptibility of clinical isolates of Pseudomonas aeruginosa from
      a Malaysian Hospital.
AB  - Ongoing surveillance of Pseudomonas aeruginosa resistance against antimicrobial
      agents is fundamental to monitor trends in susceptibility patterns and to
      appropriately guide clinicians in choosing empirical or directed therapy. The in
      vitro activity level of eight antimicrobial drugs was assessed against 97
      clinical isolates of P. aeruginosa collected consecutively for three months in
      2007 from a Malaysian hospital. Antimicrobial susceptibility was determined using
      the E-test method in addition to the hospital's routine diagnostic testing by the
      disk diffusion method. Respiratory and wound swab isolates were the most
      frequently encountered isolates. The E-test and disk diffusion methods showed
      high concordance in determining the in vitro activity of the antimicrobial agents
      against the E isolates. Piperacillin-tazobactam was the most active antimicrobial
      agent with 91.8% susceptibility, followed by the aminoglycosides (amikacin, 86.6%
      and gentamicin, 84.5%), the quinolone (ciprofloxacin, 83.5%) and the beta-lactams
      (cefepime, 80.4%, ceftazidime, 80.4%, imipenem, 79.4% and meropenem, 77.3%).
      Incidence of multidrug resistance was 19.6% (19 out of 97 isolates). Periodic
      antibiotic resistance surveillance is fundamental to monitor changes in
      susceptibility patterns in a hospital setting.

PMID- 22589656
TI  - Theophylline toxicity: A case report of the survival of an undiagnosed patient
      who presented to the emergency department.
AB  - Theophylline toxicity is a life-threatening toxidrome that can present to an
      emergency department. To ascertain an immediate provisional diagnosis in
      toxicology at the emergency department is very challenging, especially when the
      patient presents with altered mental status, because the clinical features of
      several toxidromes overlap. We report a case of survival of undiagnosed
      theophylline toxicity that required intubation for two days in the intensive care
      unit. This was the first case to have been reported from our department. Accurate
      diagnosis of a toxidrome by gaining adequate history and conducting a thorough
      physical examination and early serum toxicology screening, coupled with good
      knowledge of toxicology, will lead to better patient outcomes.

PMID- 22589657
TI  - Facial nerve paralysis: a rare complication of parotid abscess.
AB  - Benign parotid neoplasm and inflammatory processes of the parotid resulting in
      facial paralysis are extremely rare. We report a 72-year-old Malay female with
      poorly-controlled diabetes mellitus who presented with a painful right parotid
      swelling associated with right facial nerve palsy. The paralysis (Grade VI, House
      and Brackmann classification) remained after six months.

PMID- 22589658
TI  - Influenza A / H1N1 Pandemic: The Scare of 2009.

PMID- 22589659
TI  - Dengue: where are we today?
AB  - Dengue is considered the main arthropod-borne viral disease of humans. In the
      last few years, an increasing number of reports of mild and severe cases have
      been reported. The growing dengue incidence observed in recent years has been
      accompanied by reports of new observations, findings and global initiatives with
      an improvement in our understanding of this phenomenon. The epidemiology and new
      clinical classification of dengue, advances in the diagnostic and pathogenesis
      knowledge, and vaccine development as well as control methods including new
      global initiatives are summarised here.

PMID- 22589660
TI  - Influence of CYP2D6 polymorphisms on symptomatology and side-effects of patients
      with schizophrenia in Malaysia.
AB  - BACKGROUND: Our objective was to investigate the association of CYP2D6
      polymorphisms with symptoms and side-effects of patients with schizophrenia.
      METHODS: The subjects were 156 patients with schizophrenia undergoing
      antipsychotic treatment at a psychiatric clinic. Patients with co-morbid
      diagnoses of substance abuse or mental retardation were excluded from the study.
      Psychopathology was evaluated using the Positive and Negative Symptoms Scale
      (PANSS). Extrapyramidal side-effects and akathisia were assessed with the Simpson
      Angus Scale (SAS) and the Barnes Akathisia Rating Scale (BARS), respectively. DNA
      was extracted from blood and subjected to PCR-genotyping. RESULTS: We found that
      CYP2D6 polymorphisms were significantly associated with a subtotal negative PANSS
      score. In addition, CYP2D6 is not related to side-effects of antipsychotic
      therapy, or SAS and BARS scores. The results suggest that CYP2D6 polymorphisms
      may have implications in treatment response. CONCLUSIONS: Therefore, CYP2D6 may
      be a predictor for treatment outcomes of patients with schizophrenia. However,
      further investigation is required to confirm these findings in a larger sample.

PMID- 22589662
TI  - Antiproliferative Properties of Clausine-B against Cancer Cell Lines.
AB  - BACKGROUND: CLAUSINE B, A CARBAZOLE ALKALOID ISOLATED FROM THE STEM BARK OF
      CLAUSENA EXCAVATA, WAS INVESTIGATED FOR ITS ANTIPROLIFERATIVE ACTIVITIES AGAINST
      FIVE HUMAN CANCER CELL LINES: HepG2 (hepatic cancer), MCF-7 (hormone-dependent
      breast cancer), MDA-MB-231 (non-hormone-dependent breast cancer), HeLa (cervical
      cancer), and CAOV3 (ovarian cancer). METHODS: Chang liver (normal cells) was used
      as a control. The effect of clausine-B was measured using the MTT (3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. RESULTS: Clausine-B
      was found to be active (IC(50)<30 MUg/mL) against four of the cancer cell lines
      tested. The IC(50) values for these four lines were: 21.50 MUg/mL (MDA-MB-231),
      22.90 g/ml (HeLa), 27.00 MUg/mL (CAOV3) and 28.94 MUg/mL (HepG2). Clausine-B
      inhibited the MCF-7 cancer cell line at 52.90 MUg/mL, and no IC(50) value was
      obtained against Chang liver. CONCLUSION: It is possible that the phenolic group
      in clausine-B responsible for the antiproliferative activities found in this
      study.

PMID- 22589661
TI  - Molecular characterisation of Haemoglobin Constant Spring and Haemoglobin Quong
      Sze with a Combine-Amplification Refractory Mutation System.
AB  - BACKGROUND: The interaction of the non-deletional alpha(+)-thalassaemia mutations
      Haemoglobin Constant Spring and Haemoglobin Quong Sze with the Southeast Asian
      double alpha-globin gene deletion results in non-deletional Haemoglobin H
      disease. Accurate detection of non-deletional Haemoglobin H disease, which is
      associated with severe phenotypes, is necessary as these mutations have been
      confirmed in the Malaysian population. METHODS: DNA from two families with
      Haemoglobin H disease was extracted from EDTA-anticoagulated whole blood and
      subjected to molecular analysis for alpha-thalassaemia. A duplex polymerase chain
      reaction was used to detect the Southeast Asian alpha-globin gene deletion.
      Polymerase chain reaction-restriction fragment length polymorphism analysis was
      then carried out to determine the presence of Haemoglobin Constant Spring and
      Haemoglobin Quong Sze. A combine-amplification refractory mutation system
      protocol was optimised and implemented for the rapid and specific molecular
      characterisation of Haemoglobin Constant Spring and Haemoglobin Quong Sze in a
      single polymerase chain reaction. RESULTS AND CONCLUSIONS: The combine
      amplification refractory mutation system for Haemoglobin Constant Spring and
      Haemoglobin Quong Sze, together with the duplex polymerase chain reaction,
      provides accurate pre- and postnatal diagnosis of non-deletional Haemoglobin H
      disease and allows detailed genotype analyses using minimal quantities of DNA.

PMID- 22589663
TI  - Analysis of hair samples using microscopical and molecular techniques to
      ascertain claims of rare animal species.
AB  - BACKGROUND: An unidentified animal species named the Jenglot and claimed to be a
      rare living animal species was recently found in the deep jungle of Irian Jaya,
      Indonesia; brought to Kuala Lumpur, Malaysia by a businessman; and exhibited in a
      local museum. The owner of the Jenglot carcasses had made a request to perform
      DNA analysis on the Jenglot to ascertain its species. METHODS: Because the muscle
      appeared very dry and recovery of DNA was extremely difficult, we therefore used
      the animals' hair for further analysis. Hair samples were collected from three
      different Jenglots that were different in colour and physical appearance. The
      samples were labelled as A, B, C and D, respectively. RESULTS: Microscopic
      characteristics indicated that all four hair samples were of human origin, with a
      medullary index less than 1/3 and pigment distribution towards the periphery. The
      scale pattern on the hair samples was of the imbricate type, adding certainty to
      the hypothesis of human origin. A dried root sheath was found in samples B and C,
      which was contrary to expectations since the sample collection method left a few
      cm of hair on the body of the Jenglots. Sample D had black dye granules over the
      cuticular surface. Sequencing of the mitochondrial DNA (mtDNA) hypervariable
      segment I (HVS-I) region showed polymorphisms at positions 16140, 16182C, 16183C,
      16189, 16217 and 16274 and heteroplasmy at positions 16112, 16232 and 16251, a
      human-specific mtDNA haplotype that was consistent across all the samples.
      CONCLUSIONS: Based on these findings, it was concluded that it is unlikely that
      the samples of Jenglot hair originated from an animal species.

PMID- 22589664
TI  - Isosporiasis in HIV/AIDS Patients in Edo State, Nigeria.
AB  - BACKGROUND: The role of opportunistic infections in accelerating disease
      progression in HIV-positive individuals, leading to quick death, is still
      receiving serious attention. The objective of this study was to determine the
      prevalence of Isospora belli infections in HIV-positive patients in Edo State,
      Nigeria between August 2007 and March 2008. METHODS: A total of 268 samples from
      HIV-positive patients and 20 samples from HIV-negative patients were processed
      using the modified Ziehl-Neelsen staining technique to microscopically identify
      the presence of I. belli oocysts. RESULTS: The overall prevalence of the
      coccidian was 3.1%. Gender and age had no correlation with the prevalence of the
      parasite (P > 0.05). There was a significant relationship between isosporiasis
      and CD4+ T cell counts in HIV-positive patients (OR=11.388, 95% CI= 2.797-46.371,
      P=0.0004). CONCLUSIONS: Routine investigation of I. belli in HIV-positive
      subjects is advocated in tertiary health institutions.

PMID- 22589665
TI  - Emergency thyroidectomy for a bleeding multinodular goitre.
AB  - Goitre is a slow-growing thyroid mass, rarely presenting as an emergency.
      However, a superimposed infection or acute intralesional bleeding can cause the
      mass to increase rapidly in size. We report a patient with long-standing
      multinodular goitre who presented with bleeding from the left thyroid mass.
      Despite all appropriate measures, the continuous bleeding finally stopped upon
      thyroidectomy.

PMID- 22589666
TI  - Anterior stabilisation of sacroilliac joint for complex pelvic injuries.
AB  - Sacroilliac joint diasthesis from high energy trauma is always complicated with
      chronic pain and long term morbidity. Open anterior stabilisation with plate
      allow direct reduction and stabilisation with biomechanically advantages. Here we
      report on four cases of pelvic injury with sacroiliac joint disruption treated
      with anterior plate stabilisation through a surgical approach similar to that
      used for anterior ring fractures.

PMID- 22589667
TI  - Interesting asian plants: their compounds and effects on electrophysiology and
      behaviour.
AB  - There have been numerous non-scientific reports on the behavioural effects of
      Asian plants in humans who consumed these plants wholly or part thereof.
      Knowledge passed from generation to generation informs us of plants that increase
      effort and stamina, such as during paddy planting after the ingestion of
      Mitragyna speciosa Korth (ketum) as a tea supplement. Centella asiatica and
      Myristica fragrans are used as herbs to improve memory and to treat epilepsy,
      respectively. Zizyphus mauritiana is used to treat headache and burn pain, acts
      as an antitussive, and reduces rigor mortis immediately after death. These
      plants, which have been identified to exhibit analgaesic, muscle-relaxing, and
      nootropic effects, may contain important bio-compounds for medicinal chemistry
      and pharmaceutical research in Malaysia. The electrophysiology properties of
      these plants and their effects on epilepsy, behaviour, and pain will lead
      Malaysia to future new drug discoveries.

PMID- 22589668
TI  - The importance of animal models in tuberculosis vaccine development.
AB  - Research, development, and production of vaccines are still highly dependent on
      the use of animal models in the various evaluation steps. Despite this fact,
      there are strong interests and ongoing efforts to reduce the use of animals in
      vaccine development. Tuberculosis vaccine development is one important example of
      the complexities involved in the use of animal models for the production of new
      vaccines. This review summarises some of the general aspects related with the use
      of animals in vaccine research and production, as well as achievements and
      challenges towards the rational use of animals, particularly in the case of
      tuberculosis vaccine development.

PMID- 22589669
TI  - The in vitro antimicrobial activities of metabolites from lactobacillus strains
      on Candida species implicated in Candida vaginitis.
AB  - BACKGROUND: Research from developing countries, such as Nigeria, on Lactobacillus
      species in the female urogenital tract and their role as a barrier to vaginal
      infection is limited. Therefore, the aim of this study was to assess the clinical
      biotherapeutic potential of indigenous Lactobacillus species. METHODS:
      Antimicrobial metabolites production were characterised using simple and easily
      reproducible qualitative and quantitative methods. The in vitro inhibitory effect
      of Lactobacillus antimicrobials on vulvovaginal candidiasis-associated Candida
      species was investigated using modified agar spot and agar well-diffusion
      methods. RESULTS: The maximum levels of lactic acid, hydrogen peroxide, and
      diacetyl from 20 vaginal Lactobacillus strains from diseased subjects were 1.46
      mg/L, 1.36 mmol/L, and 1.72 mg/L respectively. From the 4 healthy subjects, the
      maximum level of lactic acid was 1.08 mg/L; hydrogen peroxide, 1.36 mmol/L; and
      diacetyl, 0.86 mg/L. The maximum productions of these substances occurred between
      72 and 120 hours of incubation. The in vitro antagonistic activities of vaginal
      L. acidophilus, L. fermentum, L. brevis, L. plantarum, L. casei, L. delbrueckii,
      and L. jensenii from diseased subjects inhibited a maximum of 5.71% of the 35
      Candida species tested, while vaginal L. acidophilus and L. plantarum from
      healthy subjects inhibited between 57.1% and 68.6% of Candida species in vitro.
      CONCLUSION: Antimicrobial-producing lactobacilli can be considered as adjunct
      biotherapeutic candidates for the treatment of vulvovaginal candidiasis.

PMID- 22589670
TI  - Effects of duration of diabetes on behavioural and cognitive parameters in
      streptozotocin-induced juvenile diabetic rats.
AB  - BACKGROUND: Diabetic encephalopathy is a recently recognised complication of
      early-onset type 1 diabetes in children. The abnormalities underlying diabetic
      encephalopathy are complex and poorly understood, and the impact of disease
      duration on behavioural and cognitive parameters also remains unclear. Hence, the
      present study was conducted to determine the effects of different durations of
      hyperglycaemia on behavioural and cognitive parameters in young streptozotocin
      induced diabetic rats. METHODS: Diabetes was induced in young, weaned, age
      matched rat pups by streptozotocin injection (50 mg/kg body weight,
      intraperitoneally). Diabetic status was confirmed on post-natal day 30. The rats
      were tested in the elevated plus maze 10 and 2o days after diabetes induction.
      RESULTS: Diabetic rats had significantly impaired behavioural and cognitive
      functions compared with age-matched controls. Increased anxiety levels and
      cognitive deficits were observed in rats that had been diabetic for 20 days
      compared with their 10-day counterparts. CONCLUSION: It is essential to diagnose
      and treat early-onset type 1 diabetes in young children to prevent irreversible
      cognitive dysfunction.

PMID- 22589671
TI  - Using pharmacoeconomic modelling to determine value-based pricing for new
      pharmaceuticals in malaysia.
AB  - BACKGROUND: Decision analysis (DA) is commonly used to perform economic
      evaluations of new pharmaceuticals. Using multiples of Malaysia's per capita 2010
      gross domestic product (GDP) as the threshold for economic value as suggested by
      the World Health Organization (WHO), DA was used to estimate a price per dose for
      bevacizumab, a drug that provides a 1.4-month survival benefit in patients with
      metastatic colorectal cancer (mCRC). METHODS: A decision model was developed to
      simulate progression-free and overall survival in mCRC patients receiving
      chemotherapy with and without bevacizumab. Costs for chemotherapy and management
      of side effects were obtained from public and private hospitals in Malaysia.
      Utility estimates, measured as quality-adjusted life years (QALYs), were
      determined by interviewing 24 oncology nurses using the time trade-off technique.
      The price per dose was then estimated using a target threshold of US$44 400 per
      QALY gained, which is 3 times the Malaysian per capita GDP. RESULTS: A cost
      effective price for bevacizumab could not be determined because the survival
      benefit provided was insufficient According to the WHO criteria, if the drug was
      able to improve survival from 1.4 to 3 or 6 months, the price per dose would be
      $567 and $1258, respectively. CONCLUSION: The use of decision modelling for
      estimating drug pricing is a powerful technique to ensure value for money. Such
      information is of value to drug manufacturers and formulary committees because it
      facilitates negotiations for value-based pricing in a given jurisdiction.

PMID- 22589672
TI  - A Nested Allele-Specific Multiplex Polymerase Chain Reaction Method for the
      Detection of DRD2 Polymorphisms.
AB  - BACKGROUND: The dopamine D2 receptor gene (DRD2) plays a role in many diseases
      such as schizophrenia, Parkinson's disease, and addictive behaviour. Methods
      currently available for the detection of DRD2 polymorphisms are costly and cannot
      detect all 8 polymorphisms of our research interest simultaneously (Val96Ala,
      Leu141Leu, Val154Ile, Pro310Ser, Ser311Cys, TaqI A, A-241G, and -141C Ins/Del).
      Therefore, we developed a nested multiplex polymerase chain reaction (PCR) for
      simultaneous detection of these polymorphisms. METHODS: Genomic DNA was extracted
      from blood using standardised methods. Primers specific at the 3'-end for the
      polymorphic sites were designed. A two-step PCR method was developed. In the
      first PCR, a region from exon 3 to 4, exon 7, the promoter region, and the 3'
      region of DRD2 were specifically amplified. The products were subsequently used
      as templates in the second PCR. Sequencing was performed to validate the test
      results. RESULTS: Specific bands corresponding to the amplified product of
      interest were obtained. The method was reproducible and specific when used to
      genotype patients with schizophrenia. The amplified sequences showed 100%
      homology to the DRD2 sequence. CONCLUSION: The method was found to be simple,
      rapid, specific, and reproducible for the simultaneous detection of the DRD2
      polymorphisms.

PMID- 22589673
TI  - Neurodevelopmental outcome of newborns with persistent pulmonary hypertension.
AB  - BACKGROUND: Developmental disabilities have been reported in infants with
      persistent pulmonary hypertension of the newborn (PPHN) treated with inhaled
      nitric oxide (INO) or intravenous magnesium sulphate (MgSO(4)) and/or
      extracorporeal membrane oxygenation. This paper reports the rate of developmental
      disabilities at 2 years of age in a cohort of survivors of PPHN treated with INO,
      MgSO(4), or both during the neonatal period. METHODS: Sixteen survivors of PPHN
      were prospectively followed up. These infants were treated with intravenous
      MgSO(4) and/or INO during the neonatal period. Neurodevelopmental assessment was
      carried out at 2 years of age using the Bayley Scales of Infant Development 2nd
      Edition by a developmental psychologist. Eleven (68.8%) infants completed the 2
      year follow-up. RESULTS: The median mental developmental index (MDI) and physical
      developmental index scores were 85 (interquartile range, IQR = 27) and 87 (IQR =
      33), respectively. Two infants (18.2%) had developmental disability (MDI scores
      <70). CONCLUSION: Survivors of PPHN are at risk of developmental disabilities.
      Early intervention programme and long-term follow-up should be integrated in the
      management of these infants.

PMID- 22589674
TI  - A Preliminary Study on the Reliability of the Malay Version of PedsQLTM Family
      Impact Module among Caregivers of Children with Disabilities in Kelantan,
      Malaysia.
AB  - BACKGROUND: No previous study has assessed the impact of childhood disability on
      parents and family in the context of Malaysia, and no instrument to measure this
      impact has previously been available. The objective of this cross-sectional study
      was to determine the reliability of a Malay version of the PedsQLTM Family Impact
      Module that measures the impact of children with disabilities (CWD) on their
      parents and family in a Malaysian context. METHODS: The study was conducted in
      2009. The questionnaire was translated forward and backward before it was
      administered to 44 caregivers of CWD to determine the internal consistency
      reliability. The test for Cronbach's alpha was performed. RESULTS: The internal
      consistency reliability was good. The Cronbach's alpha for all domains was above
      0.7, ranging from 0.73 to 0.895. CONCLUSION: The Malay version of the PedsQLTM
      Family Impact Module showed evidence of good internal consistency reliability.
      However, future studies with a larger sample size are necessary before the module
      can be recommended as a tool to measure the impact of disability on Malay
      speaking Malaysian families.

PMID- 22589675
TI  - An Observational Study of Blood Glucose Levels during Admission and 24 Hours Post
      Operation in a Sample of Patients with Traumatic Injury in a Hospital in Kuala
      Lumpur.
AB  - BACKGROUND: Traumatic brain injury (TBI) has been associated with an acute stress
      response mediated by the sympathoadrenomedullary axis, which can be assessed by
      measuring blood glucose level. METHODS: This prospective observational study was
      conducted for a year in 2007 among 294 patients who had been treated for TBI in
      Hospital Kuala Lumpur. Patients fulfilling the set criteria were recruited into
      the study and data, including blood glucose level and Glasgow Outcome Score at 3
      month follow-up, were collected. RESULTS: 294 patients were included in the
      study: 50 females (17.0%) and 244 males (83.0%). The majority of cases were young
      adult patients (mean age of 34.2 years, SD 13.0). The mean blood glucose level
      during admission and post-surgery were 6.26 mmol/L (SD 1.30, n = 294) and 6.66
      mmol/L (SD 1.44, n = 261), respectively. Specifically, the mean admission glucose
      level associated with mild TBI was 5.04 mmol/L (SD 0.71); moderate TBI, 5.78
      mmol/L (SD 1.02); and severe TBI, 7.04 mmol/L (SD 1.18). The mean admission
      glucose level associated with a poor outcome in patients with isolated TBI was
      6.98 mmol/L (SD 1.21). Patients with admission glucose of 5.56 mmol/L (SD 1.21)
      were more likely to have a favourable outcome. CONCLUSION: Mild, moderate, and
      severe TBI were associated with an increase in blood glucose levels during
      admission, and the mean increase in glucose levels is based on the severity of
      the isolated TBI. Surgical intervention did not cause further significant changes
      in blood glucose levels. Patients with isolated TBI and minimal increases in
      blood glucose levels were more likely to have a favourable outcome.

PMID- 22589676
TI  - Medicalisation of suicide.
AB  - Medicalisation is the misclassification of non-medical problems as medical
      problems. A common form of medicalisation is the misclassification of normal
      distress as a mental disorder (usually a mood disorder). Suicide is medicalised
      when it is considered a medical diagnosis per se, when it is considered to be
      secondary to a mental disorder when no mental disorder is present, and when no
      mental disorder is present but the management of suicidal behaviour associated
      with distress is believed to be the sole responsibility of mental health
      professionals. In the West, psychological autopsies have led to the belief that
      all or almost all suicide is the result of mental disorder. However, there are
      reservations about the scientific status of such studies. The actions of
      psychological autopsy researchers, coroners/magistrates, police, policy writers,
      and grieving relatives all contribute. Medicalisation of suicide has the
      potential to distort research findings, and caution is recommended.

PMID- 22589677
TI  - Retrocaval ureter: the importance of intravenous urography.
AB  - Retrocaval ureter is a rare cause of hydronephrosis. Its rarity and non-specific
      presentation pose a challenge to surgeons and radiologists in making the correct
      diagnosis. Differentiation from other causes of urinary tract obstruction,
      especially the more common urolithiasis, is important for successful surgical
      management. Current practice has seen multislice computed tomography (MSCT)
      rapidly replaces intravenous urography (IVU) in the assessment of patients with
      hydronephrosis due to suspected urolithiasis, especially ureterolithiasis.
      However, MSCT, without adequate opacification of the entire ureter, may allow the
      physician to overlook a retrocaval ureter as the cause of hydronephrosis. High
      resolution IVU images can demonstrate the typical appearance that leads to the
      accurate diagnosis of a retrocaval ureter. We reported a case that illustrates
      this scenario and highlights the importance of IVU in the assessment of a complex
      congenital disorder involving the urinary tract.

PMID- 22589678
TI  - Kimura's Disease: A Rare Cause of Nephrotic Syndrome with Lymphadenopathy.
AB  - Kimura's disease is a rare condition and typically presents as non-tender
      subcutaneous swellings in the head and neck region, usually in the pre-auricular
      and submandibular areas. It is associated with lymphadenopathy (both local and
      distal), marked peripheral eosinophilia, and an elevated IgE level. It can easily
      be mistaken for a malignant disorder. Fine needle aspiration can be misleading,
      and a diagnosis is established only by histopathological examination. Renal
      involvement, which may affect up to 60% of patients, is the only systemic
      manifestation. We report a case of Kimura's disease in a Malay patient who was
      associated with steroid-responsive nephrotic syndrome.

PMID- 22589679
TI  - Y-stent-assisted coil embolisation of wide-necked aneurysms using a new fully
      retrievable and detachable intracranial stent: report of two cases.
AB  - Endovascular treatment of wide-necked aneurysms poses a challenge for the
      endovascular therapist. The Y-stent-assisted technique has been used for stent
      assisted coil embolisation for wide-necked bifurcation aneurysms. This technique
      has been described for basilar tip aneurysms and middle cerebral artery
      bifurcation aneurysms using Neuroform and Enterprise stents. We report 2 cases of
      wide-necked bifurcation aneurysms that were treated with Y-stent-assisted coil
      embolisation using a new, fully retrievable and detachable intracranial stent
      (Solitaire ABTM). We describe the advantages of a fully retrievable and
      detachable stent and its feasibility of forming a Y configuration.

PMID- 22589680
TI  - The vanishing veins: difficult venous access in a patient requiring translumbar,
      transhepatic, and transcollateral central catheter insertion.
AB  - Central venous catheter placement is indicated in patients requiring long-term
      therapy. With repeated venous catheterisations, conventional venous access sites
      can be exhausted. This case illustrates the expanding role of radiology in
      managing difficult venous access. We present a case of translumbar, transhepatic,
      and transcollateral placement of central catheter in a woman with a difficult
      venous access problem who required lifelong parenteral nutrition secondary to
      short bowel syndrome. This case highlights the technical aspects of
      interventional radiology in vascular access management.

PMID- 22589681
TI  - Communication in medical practice - surfeit or dearth.

PMID- 22589682
TI  - Effect of nicardipine on fasting plasma lipids and apolipoproteins in male new
      zealand white rabbits.
AB  - The effect of nicardipine on fasting plasma lipid profiles was studied in rabbits
      given a 2% cholesterol diet. Twenty four New Zealand White rabbits (2.2 - 2.8 kg)
      were divided into 3 groups. Group 1 (control) was fed a normal diet, group II
      (HC) was fed a 2% cholesterol diet and group III (HC+NICA) was fed a 2%
      cholesterol diet with nicardipine treatment (0.5mg kg(-1) body weight twice daily
      intramuscularly for 10 weeks). The following parameters which included fasting
      plasma total cholesterol, triglycerides, HDL cholesterol and apolipoprotein A and
      B were measured before and after 10 weeks of study. In the present study we
      observed that a 2% cholesterol diet caused a significant increase in plasma total
      cholesterol, LDL cholesterol, HDL cholesterol and triglycerides. However, the
      increase in total cholesterol and LDL cholesterol were not prevented by treatment
      with nicardipine. Nicardipine appeared to cause further increase in HDL
      cholesterol and prevented further rise in plasma triglycerides after 10 weeks of
      treatment.

PMID- 22589683
TI  - The use of electronic sensor in hormone analysis.
AB  - The development of antibody-based biosensor has grown steadily during recent
      years, and their use as a routine instrument in clinical application is not far
      from reality. This study has demonstrated the capability of conductometric sensor
      to quantitate human Follicle Stimulating Hormone (hFSH) from urine samples. The
      principles are adopted from Enzyme Linked Immunosorbent Assay (ELISA) technique.
      Self fabricated gold coated electrode was dipped in the microtiter well
      containing antibody-antigen complex. Substrate was added to the system to
      initiate a secondary reaction, which produced electroactive species and change
      the conductivity of the solution. The changes were proportional with the
      concentration of the hormone present. The results obtained correlate well with
      the conventional ELISA technique. Inter and intra assay variation (%CV) were
      under 6% and the lowest detection limit is 0.75 mIU/ml which was well under the
      physiological range of the hormone. This system offered advantages such as
      simplicity, reliability, minimal addition of reagents, freedom from turbidity and
      color problem, probability of miniaturizing the electrode thus minimizing the
      sample volume and the ability of on line data analysis. This study proved that
      Antigen-Antibody reaction via EIA could be detected electronically and it has a
      potential to be used as one of the measuring mode in clinical analysis.

PMID- 22589684
TI  - Antimicrobial effects of psidium guajava extract as one mechanism of its
      antidiarrhoeal action.
AB  - A morphine-like spasmolytic action (not naloxone reversible; involving the
      inhibition of acetylcholine release) and also effects on the transmural transport
      of electrolytes (Na(+) and K(+)) and water have been reported as possible modes
      of the antidiarrhoeal action of polar fractions of Psidium guajava leaf
      extractives. The objective for this study was to verify if the reported modes of
      the antidiarrhoeal action should be broadened to include direct antimicrobial
      actions on some of the more common bacteria known to cause toxin-induced acute
      diarrhoea. Serial dilutions of a water-soluble, freeze-dried methanolic extract
      were tested on 10 such organisms, grown separately on nutrient agar plates, to
      determine the minimum inhibitory concentration (MIC) for each of these bacteria.
      These included the causative agents for (i) enteric fever (Salmonella typhi,
      Salmonella paratyphi A, Salmonella paratyphi B and Salmonella paratyphi C), (ii)
      food poisoning (Salmonella typhimurium and Staphylococcus aureus), (iii)
      dysentery (Shigella dysenteriae, Shigella flexneri and Shigella sonnei), and (iv)
      cholera (Vibrio cholerae). The growth of all these organisms was inhibited at the
      MIC of 10mg/ml of the extract, which is equivalent to 2.5MUg/ml of active
      extractable flavonoids. The most sensitive organisms (MIC = 1mg/ml) were
      Staphylococcus aureus, Vibrio cholerae and Shigella flexneri.

PMID- 22589685
TI  - The pilot study of whoqol-100 (malay version).
AB  - In confronting the advances in the new treatment for incurable illnesses there is
      an increasing need for doctors to be aware of their patients' cognition and
      feeling related to their quality of life (QOL). Recognizing this need the authors
      translated and pilot tested the WHOQOL-100, a genuinely international measure of
      QOL by the World Health Organization (quality of life group). The WHOQOL-100
      Malay version was pilot tested on 50 healthy controls and 250 ill subjects,
      suffering from hypertension, diabetes mellitus, those suffering from both
      hypertension and ischaemic heart disease, epilepsy and schizophrenia. The results
      showed several unique features of the QOL, which were influenced by different
      types of illnesses. The information obtained is different and probably not
      observable from clinical consultations. This study will be an impetus for further
      studies using the WHOQOL-100 assessment tool in the local population.

PMID- 22589686
TI  - Breast cancer after augmentation mammoplasty with silicone gel-filled implant: a
      case report.
AB  - A 47 year old Chinese housewife with a silicone gel-filled implant mammoplasty
      carried out 10 years ago presented with a palpable painless lump in the right
      breast. Excision biopsy revealed infiltrating ductal carcinoma. Right simple
      mastectomy and axillary sampling was done followed by chemotherapy and
      radiotherapy. The history, safety, potential complications of silicone breast
      implants are reviewed and discussed.

PMID- 22589687
TI  - Munchausen syndrome by proxy.
AB  - Munchausen syndrome by proxy is a rare disorder in child psychiatric practice. A
      case of Munchausen syndrome by proxy that was managed in the Child Psychiatric
      clinic, Universiti Sains Malaysia Hospital is reported. Factors that suggest the
      diagnosis are discussed. Multidisciplinary approach to the management of such
      cases is warranted.

PMID- 22589698
TI  - Bit by bit: the Darwinian basis of life.
AB  - All known examples of life belong to the same biology, but there is increasing
      enthusiasm among astronomers, astrobiologists, and synthetic biologists that
      other forms of life may soon be discovered or synthesized. This enthusiasm should
      be tempered by the fact that the probability for life to originate is not known.
      As a guiding principle in parsing potential examples of alternative life, one
      should ask: How many heritable "bits" of information are involved, and where did
      they come from? A genetic system that contains more bits than the number that
      were required to initiate its operation might reasonably be considered a new form
      of life.

PMID- 22589699
TI  - Enhancement of asynchronous release from fast-spiking interneuron in human and
      rat epileptic neocortex.
AB  - Down-regulation of GABAergic inhibition may result in the generation of
      epileptiform activities. Besides spike-triggered synchronous GABA release,
      changes in asynchronous release (AR) following high-frequency discharges may
      further regulate epileptiform activities. In brain slices obtained from
      surgically removed human neocortical tissues of patients with intractable
      epilepsy and brain tumor, we found that AR occurred at GABAergic output synapses
      of fast-spiking (FS) neurons and its strength depended on the type of
      connections, with FS autapses showing the strongest AR. In addition, we found
      that AR depended on residual Ca2+ at presynaptic terminals but was independent of
      postsynaptic firing. Furthermore, AR at FS autapses was markedly elevated in
      human epileptic tissue as compared to non-epileptic tissue. In a rat model of
      epilepsy, we found similar elevation of AR at both FS autapses and synapses onto
      excitatory neurons. Further experiments and analysis showed that AR elevation in
      epileptic tissue may result from an increase in action potential amplitude in the
      FS neurons and elevation of residual Ca2+ concentration. Together, these results
      revealed that GABAergic AR occurred at both human and rat neocortex, and its
      elevation in epileptic tissue may contribute to the regulation of epileptiform
      activities.

PMID- 22589702
TI  - Yeast survive by hedging their bets.
AB  - A new experimental approach reveals a bet hedging strategy in unstressed, clonal
      yeast cells, whereby they adopt a range of growth states that correlate with
      expression of a trehalose-synthesis regulator and predict resistance to future
      stress.

PMID- 22589700
TI  - Bet hedging in yeast by heterogeneous, age-correlated expression of a stress
      protectant.
AB  - Genetically identical cells grown in the same culture display striking cell-to
      cell heterogeneity in gene expression and other traits. A crucial challenge is to
      understand how much of this heterogeneity reflects the noise tolerance of a
      robust system and how much serves a biological function. In bacteria, stochastic
      gene expression results in cell-to-cell heterogeneity that might serve as a bet
      hedging mechanism, allowing a few cells to survive through an antimicrobial
      treatment while others perish. Despite its clinical importance, the molecular
      mechanisms underlying bet hedging remain unclear. Here, we investigate the
      mechanisms of bet hedging in Saccharomyces cerevisiae using a new high-throughput
      microscopy assay that monitors variable protein expression, morphology, growth
      rate, and survival outcomes of tens of thousands of yeast microcolonies
      simultaneously. We find that clonal populations display broad distributions of
      growth rates and that slow growth predicts resistance to heat killing in a
      probabalistic manner. We identify several gene products that are likely to play a
      role in bet hedging and confirm that Tsl1, a trehalose-synthesis regulator, is an
      important component of this resistance. Tsl1 abundance correlates with growth
      rate and replicative age and predicts survival. Our results suggest that yeast
      bet hedging results from multiple epigenetic growth states determined by a
      combination of stochastic and deterministic factors.

PMID- 22589701
TI  - Novel role of NOX in supporting aerobic glycolysis in cancer cells with
      mitochondrial dysfunction and as a potential target for cancer therapy.
AB  - Elevated aerobic glycolysis in cancer cells (the Warburg effect) may be
      attributed to respiration injury or mitochondrial dysfunction, but the underlying
      mechanisms and therapeutic significance remain elusive. Here we report that
      induction of mitochondrial respiratory defect by tetracycline-controlled
      expression of a dominant negative form of DNA polymerase gamma causes a metabolic
      shift from oxidative phosphorylation to glycolysis and increases ROS generation.
      We show that upregulation of NOX is critical to support the elevated glycolysis
      by providing additional NAD+. The upregulation of NOX is also consistently
      observed in cancer cells with compromised mitochondria due to the activation of
      oncogenic Ras or loss of p53, and in primary pancreatic cancer tissues.
      Suppression of NOX by chemical inhibition or genetic knockdown of gene expression
      selectively impacts cancer cells with mitochondrial dysfunction, leading to a
      decrease in cellular glycolysis, a loss of cell viability, and inhibition of
      cancer growth in vivo. Our study reveals a previously unrecognized function of
      NOX in cancer metabolism and suggests that NOX is a potential novel target for
      cancer treatment.

PMID- 22589703
TI  - Six-year follow-up of impact of co-proxamol withdrawal in England and Wales on
      prescribing and deaths: time-series study.
AB  - BACKGROUND: The analgesic co-proxamol (paracetamol/dextropropoxyphene
      combination) has been widely involved in fatal poisoning. Concerns about its
      safety/effectiveness profile and widespread use for suicidal poisoning prompted
      its withdrawal in the UK in 2005, with partial withdrawal between 2005 and 2007,
      and full withdrawal in 2008. Our objective in this study was to assess the
      association between co-proxamol withdrawal and prescribing and deaths in England
      and Wales in 2005-2010 compared with 1998-2004, including estimation of possible
      substitution effects by other analgesics. METHODS AND FINDINGS: We obtained
      prescribing data from the NHS Health and Social Care Information Centre (England)
      and Prescribing Services Partneriaeth Cydwasanaethau GIG Cymru (Wales), and
      mortality data from the Office for National Statistics. We carried out an
      interrupted time-series analysis of prescribing and deaths (suicide, open
      verdicts, accidental poisonings) involving single analgesics. The reduction in
      prescribing of co-proxamol following its withdrawal in 2005 was accompanied by
      increases in prescribing of several other analgesics (co-codamol, paracetamol,
      codeine, co-dydramol, tramadol, oxycodone, and morphine) during 2005-2010
      compared with 1998-2004. These changes were associated with major reductions in
      deaths due to poisoning with co-proxamol receiving verdicts of suicide and
      undetermined cause of -21 deaths (95% CI -34 to -8) per quarter, equating to
      approximately 500 fewer suicide deaths (-61%) over the 6 years 2005-2010, and -25
      deaths (95% CI -38 to -12) per quarter, equating to 600 fewer deaths (-62%) when
      accidental poisoning deaths were included. There was little observed change in
      deaths involving other analgesics, apart from an increase in oxycodone
      poisonings, but numbers were small. Limitations were that the study was based on
      deaths involving single drugs alone and changes in deaths involving prescribed
      morphine could not be assessed. CONCLUSIONS: During the 6 years following the
      withdrawal of co-proxamol in the UK, there was a major reduction in poisoning
      deaths involving this drug, without apparent significant increase in deaths
      involving other analgesics.

PMID- 22589704
TI  - Does development assistance for health really displace government health
      spending? Reassessing the evidence.

PMID- 22589705
TI  - Criminal justice reform as HIV and TB prevention in African prisons.

PMID- 22589706
TI  - NIBBS-search for fast and accurate prediction of phenotype-biased metabolic
      systems.
AB  - Understanding of genotype-phenotype associations is important not only for
      furthering our knowledge on internal cellular processes, but also essential for
      providing the foundation necessary for genetic engineering of microorganisms for
      industrial use (e.g., production of bioenergy or biofuels). However, genotype
      phenotype associations alone do not provide enough information to alter an
      organism's genome to either suppress or exhibit a phenotype. It is important to
      look at the phenotype-related genes in the context of the genome-scale network to
      understand how the genes interact with other genes in the organism.
      Identification of metabolic subsystems involved in the expression of the
      phenotype is one way of placing the phenotype-related genes in the context of the
      entire network. A metabolic system refers to a metabolic network subgraph; nodes
      are compounds and edges labels are the enzymes that catalyze the reaction. The
      metabolic subsystem could be part of a single metabolic pathway or span parts of
      multiple pathways. Arguably, comparative genome-scale metabolic network analysis
      is a promising strategy to identify these phenotype-related metabolic subsystems.
      Network Instance-Based Biased Subgraph Search (NIBBS) is a graph-theoretic method
      for genome-scale metabolic network comparative analysis that can identify
      metabolic systems that are statistically biased toward phenotype-expressing
      organismal networks. We set up experiments with target phenotypes like hydrogen
      production, TCA expression, and acid-tolerance. We show via extensive literature
      search that some of the resulting metabolic subsystems are indeed phenotype
      related and formulate hypotheses for other systems in terms of their role in
      phenotype expression. NIBBS is also orders of magnitude faster than MULE, one of
      the most efficient maximal frequent subgraph mining algorithms that could be
      adjusted for this problem. Also, the set of phenotype-biased metabolic systems
      output by NIBBS comes very close to the set of phenotype-biased subgraphs output
      by an exact maximally-biased subgraph enumeration algorithm ( MBS-Enum ). The
      code (NIBBS and the module to visualize the identified subsystems) is available
      at http://freescience.org/cs/NIBBS.

PMID- 22589707
TI  - Intermittent motion in desert locusts: behavioural complexity in simple
      environments.
AB  - Animals can exhibit complex movement patterns that may be the result of
      interactions with their environment or may be directly the mechanism by which
      their behaviour is governed. In order to understand the drivers of these patterns
      we examine the movement behaviour of individual desert locusts in a homogenous
      experimental arena with minimal external cues. Locust motion is intermittent and
      we reveal that as pauses become longer, the probability that a locust changes
      direction from its previous direction of travel increases. Long pauses (of
      greater than 100 s) can be considered reorientation bouts, while shorter pauses
      (of less than 6 s) appear to act as periods of resting between displacements. We
      observe power-law behaviour in the distribution of move and pause lengths of over
      1.5 orders of magnitude. While Levy features do exist, locusts' movement patterns
      are more fully described by considering moves, pauses and turns in combination.
      Further analysis reveals that these combinations give rise to two behavioural
      modes that are organized in time: local search behaviour (long exploratory pauses
      with short moves) and relocation behaviour (long displacement moves with shorter
      resting pauses). These findings offer a new perspective on how complex animal
      movement patterns emerge in nature.

PMID- 22589708
TI  - Virus capsid dissolution studied by microsecond molecular dynamics simulations.
AB  - Dissolution of many plant viruses is thought to start with swelling of the capsid
      caused by calcium removal following infection, but no high-resolution structures
      of swollen capsids exist. Here we have used microsecond all-atom molecular
      simulations to describe the dynamics of the capsid of satellite tobacco necrosis
      virus with and without the 92 structural calcium ions. The capsid expanded 2.5%
      upon removal of the calcium, in good agreement with experimental estimates. The
      water permeability of the native capsid was similar to that of a phospholipid
      membrane, but the permeability increased 10-fold after removing the calcium,
      predominantly between the 2-fold and 3-fold related subunits. The two calcium
      binding sites close to the icosahedral 3-fold symmetry axis were pivotal in the
      expansion and capsid-opening process, while the binding site on the 5-fold axis
      changed little structurally. These findings suggest that the dissociation of the
      capsid is initiated at the 3-fold axis.

PMID- 22589709
TI  - Prediction of drug-target interactions and drug repositioning via network-based
      inference.
AB  - Drug-target interaction (DTI) is the basis of drug discovery and design. It is
      time consuming and costly to determine DTI experimentally. Hence, it is necessary
      to develop computational methods for the prediction of potential DTI. Based on
      complex network theory, three supervised inference methods were developed here to
      predict DTI and used for drug repositioning, namely drug-based similarity
      inference (DBSI), target-based similarity inference (TBSI) and network-based
      inference (NBI). Among them, NBI performed best on four benchmark data sets. Then
      a drug-target network was created with NBI based on 12,483 FDA-approved and
      experimental drug-target binary links, and some new DTIs were further predicted.
      In vitro assays confirmed that five old drugs, namely montelukast, diclofenac,
      simvastatin, ketoconazole, and itraconazole, showed polypharmacological features
      on estrogen receptors or dipeptidyl peptidase-IV with half maximal inhibitory or
      effective concentration ranged from 0.2 to 10 uM. Moreover, simvastatin and
      ketoconazole showed potent antiproliferative activities on human MDA-MB-231
      breast cancer cell line in MTT assays. The results indicated that these methods
      could be powerful tools in prediction of DTIs and drug repositioning.

PMID- 22589710
TI  - Filament compliance influences cooperative activation of thin filaments and the
      dynamics of force production in skeletal muscle.
AB  - Striated muscle contraction is a highly cooperative process initiated by Ca2+
      binding to the troponin complex, which leads to tropomyosin movement and myosin
      cross-bridge (XB) formation along thin filaments. Experimental and computational
      studies suggest skeletal muscle fiber activation is greatly augmented by
      cooperative interactions between neighboring thin filament regulatory units (RU
      RU cooperativity; 1 RU = 7 actin monomers+1 troponin complex+1 tropomyosin
      molecule). XB binding can also amplify thin filament activation through
      interactions with RUs (XB-RU cooperativity). Because these interactions occur
      with a temporal order, they can be considered kinetic forms of cooperativity. Our
      previous spatially-explicit models illustrated that mechanical forms of
      cooperativity also exist, arising from XB-induced XB binding (XB-XB
      cooperativity). These mechanical and kinetic forms of cooperativity are likely
      coordinated during muscle contraction, but the relative contribution from each of
      these mechanisms is difficult to separate experimentally. To investigate these
      contributions we built a multi-filament model of the half sarcomere, allowing RU
      activation kinetics to vary with the state of neighboring RUs or XBs. Simulations
      suggest Ca2+ binding to troponin activates a thin filament distance spanning 9 to
      11 actins and coupled RU-RU interactions dominate the cooperative force response
      in skeletal muscle, consistent with measurements from rabbit psoas fibers. XB
      binding was critical for stabilizing thin filament activation, particularly at
      submaximal Ca2+ levels, even though XB-RU cooperativity amplified force less than
      RU-RU cooperativity. Similar to previous studies, XB-XB cooperativity scaled
      inversely with lattice stiffness, leading to slower rates of force development as
      stiffness decreased. Including RU-RU and XB-RU cooperativity in this model
      resulted in the novel prediction that the force-[Ca2+] relationship can vary due
      to filament and XB compliance. Simulations also suggest kinetic forms of
      cooperativity occur rapidly and dominate early to get activation, while
      mechanical forms of cooperativity act more slowly, augmenting XB binding as force
      continues to develop.

PMID- 22589711
TI  - Modeling HIV-1 drug resistance as episodic directional selection.
AB  - The evolution of substitutions conferring drug resistance to HIV-1 is both
      episodic, occurring when patients are on antiretroviral therapy, and strongly
      directional, with site-specific resistant residues increasing in frequency over
      time. While methods exist to detect episodic diversifying selection and
      continuous directional selection, no evolutionary model combining these two
      properties has been proposed. We present two models of episodic directional
      selection (MEDS and EDEPS) which allow the a priori specification of lineages
      expected to have undergone directional selection. The models infer the sites and
      target residues that were likely subject to directional selection, using either
      codon or protein sequences. Compared to its null model of episodic diversifying
      selection, MEDS provides a superior fit to most sites known to be involved in
      drug resistance, and neither one test for episodic diversifying selection nor
      another for constant directional selection are able to detect as many true
      positives as MEDS and EDEPS while maintaining acceptable levels of false
      positives. This suggests that episodic directional selection is a better
      description of the process driving the evolution of drug resistance.

PMID- 22589712
TI  - Dynamic prestress in a globular protein.
AB  - A protein at equilibrium is commonly thought of as a fully relaxed structure,
      with the intra-molecular interactions showing fluctuations around their energy
      minimum. In contrast, here we find direct evidence for a protein as a molecular
      tensegrity structure, comprising a balance of tensed and compressed interactions,
      a concept that has been put forward for macroscopic structures. We quantified the
      distribution of inter-residue prestress in ubiquitin and immunoglobulin from all
      atom molecular dynamics simulations. The network of highly fluctuating yet
      significant inter-residue forces in proteins is a consequence of the intrinsic
      frustration of a protein when sampling its rugged energy landscape. In beta
      sheets, this balance of forces is found to compress the intra-strand hydrogen
      bonds. We estimate that the observed magnitude of this pre-compression is enough
      to induce significant changes in the hydrogen bond lifetimes; thus, prestress,
      which can be as high as a few 100 pN, can be considered a key factor in
      determining the unfolding kinetics and pathway of proteins under force. Strong
      pre-tension in certain salt bridges on the other hand is connected to the
      thermodynamic stability of ubiquitin. Effective force profiles between some side
      chains reveal the signature of multiple, distinct conformational states, and such
      static disorder could be one factor explaining the growing body of experiments
      revealing non-exponential unfolding kinetics of proteins. The design of prestress
      distributions in engineering proteins promises to be a new tool for tailoring the
      mechanical properties of made-to-order nanomaterials.

PMID- 22589714
TI  - Type III secretion in Yersinia: injectisome or not?

PMID- 22589713
TI  - Vaccines against tuberculosis: where are we and where do we need to go?
AB  - In this review we discuss recent progress in the development, testing, and
      clinical evaluation of new vaccines against tuberculosis (TB). Over the last 20
      years, tremendous progress has been made in TB vaccine research and development:
      from a pipeline virtually empty of new TB candidate vaccines in the early 1990s,
      to an era in which a dozen novel TB vaccine candidates have been and are being
      evaluated in human clinical trials. In addition, innovative approaches are being
      pursued to further improve existing vaccines, as well as discover new ones. Thus,
      there is good reason for optimism in the field of TB vaccines that it will be
      possible to develop better vaccines than BCG, which is still the only vaccine
      available against TB.

PMID- 22589715
TI  - The lipopolysaccharide core of Brucella abortus acts as a shield against innate
      immunity recognition.
AB  - Innate immunity recognizes bacterial molecules bearing pathogen-associated
      molecular patterns to launch inflammatory responses leading to the activation of
      adaptive immunity. However, the lipopolysaccharide (LPS) of the gram-negative
      bacterium Brucella lacks a marked pathogen-associated molecular pattern, and it
      has been postulated that this delays the development of immunity, creating a gap
      that is critical for the bacterium to reach the intracellular replicative niche.
      We found that a B. abortus mutant in the wadC gene displayed a disrupted LPS core
      while keeping both the LPS O-polysaccharide and lipid A. In mice, the wadC mutant
      induced proinflammatory responses and was attenuated. In addition, it was
      sensitive to killing by non-immune serum and bactericidal peptides and did not
      multiply in dendritic cells being targeted to lysosomal compartments. In contrast
      to wild type B. abortus, the wadC mutant induced dendritic cell maturation and
      secretion of pro-inflammatory cytokines. All these properties were reproduced by
      the wadC mutant purified LPS in a TLR4-dependent manner. Moreover, the core
      mutated LPS displayed an increased binding to MD-2, the TLR4 co-receptor leading
      to subsequent increase in intracellular signaling. Here we show that Brucella
      escapes recognition in early stages of infection by expressing a shield against
      recognition by innate immunity in its LPS core and identify a novel virulence
      mechanism in intracellular pathogenic gram-negative bacteria. These results also
      encourage for an improvement in the generation of novel bacterial vaccines.

PMID- 22589716
TI  - Entry of herpes simplex virus type 1 (HSV-1) into the distal axons of trigeminal
      neurons favors the onset of nonproductive, silent infection.
AB  - Following productive, lytic infection in epithelia, herpes simplex virus type 1
      (HSV-1) establishes a lifelong latent infection in sensory neurons that is
      interrupted by episodes of reactivation. In order to better understand what
      triggers this lytic/latent decision in neurons, we set up an organotypic model
      based on chicken embryonic trigeminal ganglia explants (TGEs) in a double chamber
      system. Adding HSV-1 to the ganglion compartment (GC) resulted in a productive
      infection in the explants. By contrast, selective application of the virus to
      distal axons led to a largely nonproductive infection that was characterized by
      the poor expression of lytic genes and the presence of high levels of the 2.0-kb
      major latency-associated transcript (LAT) RNA. Treatment of the explants with the
      immediate-early (IE) gene transcriptional inducer hexamethylene bisacetamide, and
      simultaneous co-infection of the GC with HSV-1, herpes simplex virus type 2 (HSV
      2) or pseudorabies virus (PrV) helper virus significantly enhanced the ability of
      HSV-1 to productively infect sensory neurons upon axonal entry. Helper-virus
      induced transactivation of HSV-1 IE gene expression in axonally-infected TGEs in
      the absence of de novo protein synthesis was dependent on the presence of
      functional tegument protein VP16 in HSV-1 helper virus particles. After the
      establishment of a LAT-positive silent infection in TGEs, HSV-1 was refractory to
      transactivation by superinfection of the GC with HSV-1 but not with HSV-2 and PrV
      helper virus. In conclusion, the site of entry appears to be a critical
      determinant in the lytic/latent decision in sensory neurons. HSV-1 entry into
      distal axons results in an insufficient transactivation of IE gene expression and
      favors the establishment of a nonproductive, silent infection in trigeminal
      neurons.

PMID- 22589717
TI  - KSHV PAN RNA associates with demethylases UTX and JMJD3 to activate lytic
      replication through a physical interaction with the virus genome.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is the cause of Kaposi's sarcoma
      and body cavity lymphomas. KSHV lytic infection produces PAN RNA, a highly
      abundant noncoding polyadenylated transcript that is retained in the nucleus. We
      recently demonstrated that PAN RNA interacts with several viral and cellular
      factors and can disregulate the expression of genes that modulate immune
      response. In an effort to define the role of PAN RNA in the context of the virus
      genome we generated a recombinant BACmid that deleted the PAN RNA locus. Because
      of the apparent duplication of the PAN RNA locus in BAC36, we generated BAC36CR,
      a recombinant BACmid that removes the duplicated region. BAC36CR was used as a
      template to delete most of the PAN RNA locus to generate BAC36CRDeltaPAN.
      BAC36CRDeltaPAN failed to produce supernatant virus and displayed a general
      decrease in mRNA accumulation of representative immediate early, early and late
      genes. Most strikingly, K-Rta expression was decreased in lytically induced
      BAC36CRDeltaPAN-containing cell lines at early and late time points post
      induction. Expression of PAN RNA in trans in BAC36CRDeltaPAN containing cells
      resulted in an increase in K-Rta expression, however K-Rta over expression failed
      to rescue BAC36CRDeltaPAN, suggesting that PAN RNA plays a wider role in virus
      replication. To investigate the role of PAN RNA in the activation of K-Rta
      expression, we demonstrate that PAN RNA physically interacts with the ORF50
      promoter. RNA chromatin immunoprecipitation assays show that PAN RNA interacts
      with demethylases JMJD3 and UTX, and the histone methyltransferase MLL2.
      Consistent with the interaction with demethylases, expression of PAN RNA results
      in a decrease of the repressive H3K27me3 mark at the ORF50 promoter. These data
      support a model where PAN RNA is a multifunctional regulatory transcript that
      controls KSHV gene expression by mediating the modification of chromatin by
      targeting the KSHV repressed genome.

PMID- 22589718
TI  - The NDR/LATS kinase Cbk1 controls the activity of the transcriptional regulator
      Bcr1 during biofilm formation in Candida albicans.
AB  - In nature, many microorganisms form specialized complex, multicellular, surface
      attached communities called biofilms. These communities play critical roles in
      microbial pathogenesis. The fungal pathogen Candida albicans is associated with
      catheter-based infections due to its ability to establish biofilms. The
      transcription factor Bcr1 is a master regulator of C. albicans biofilm
      development, although the full extent of its regulation remains unknown. Here, we
      report that Bcr1 is a phosphoprotein that physically interacts with the NDR
      kinase Cbk1 and undergoes Cbk1-dependent phosphorylation. Mutating the two
      putative Cbk1 phosphoacceptor residues in Bcr1 to alanine markedly impaired Bcr1
      function during biofilm formation and virulence in a mouse model of disseminated
      candidiasis. Cells lacking Cbk1, or any of its upstream activators, also had
      reduced biofilm development. Notably, mutating the two putative Cbk1
      phosphoacceptor residues in Bcr1 to glutamate in cbk1Delta cells upregulated the
      transcription of Bcr1-dependent genes and partially rescued the biofilm defects
      of a cbk1Delta strain. Therefore, our data uncovered a novel role of the NDR/LATS
      kinase Cbk1 in the regulation of biofilm development through the control of Bcr1.

PMID- 22589719
TI  - The Ustilago maydis effector Pep1 suppresses plant immunity by inhibition of host
      peroxidase activity.
AB  - The corn smut Ustilago maydis establishes a biotrophic interaction with its host
      plant maize. This interaction requires efficient suppression of plant immune
      responses, which is attributed to secreted effector proteins. Previously we
      identified Pep1 (Protein essential during penetration-1) as a secreted effector
      with an essential role for U. maydis virulence. pep1 deletion mutants induce
      strong defense responses leading to an early block in pathogenic development of
      the fungus. Using cytological and functional assays we show that Pep1 functions
      as an inhibitor of plant peroxidases. At sites of Deltapep1 mutant penetrations,
      H2O2 strongly accumulated in the cell walls, coinciding with a transcriptional
      induction of the secreted maize peroxidase POX12. Pep1 protein effectively
      inhibited the peroxidase driven oxidative burst and thereby suppresses the early
      immune responses of maize. Moreover, Pep1 directly inhibits peroxidases in vitro
      in a concentration-dependent manner. Using fluorescence complementation assays,
      we observed a direct interaction of Pep1 and the maize peroxidase POX12 in vivo.
      Functional relevance of this interaction was demonstrated by partial
      complementation of the Deltapep1 mutant defect by virus induced gene silencing of
      maize POX12. We conclude that Pep1 acts as a potent suppressor of early plant
      defenses by inhibition of peroxidase activity. Thus, it represents a novel
      strategy for establishing a biotrophic interaction.

PMID- 22589720
TI  - The effect of human factor H on immunogenicity of meningococcal native outer
      membrane vesicle vaccines with over-expressed factor H binding protein.
AB  - The binding of human complement inhibitors to vaccine antigens in vivo could
      diminish their immunogenicity. A meningococcal ligand for the complement down
      regulator, factor H (fH), is fH-binding protein (fHbp), which is specific for
      human fH. Vaccines containing recombinant fHbp or native outer membrane vesicles
      (NOMV) from mutant strains with over-expressed fHbp are in clinical development.
      In a previous study in transgenic mice, the presence of human fH impaired the
      immunogenicity of a recombinant fHbp vaccine. In the present study, we prepared
      two NOMV vaccines from mutant group B strains with over-expressed wild-type fHbp
      or an R41S mutant fHbp with no detectable fH binding. In wild-type mice in which
      mouse fH did not bind to fHbp in either vaccine, the NOMV vaccine with wild-type
      fHbp elicited 2-fold higher serum IgG anti-fHbp titers (P = 0.001) and 4-fold
      higher complement-mediated bactericidal titers against a PorA-heterologous strain
      than the NOMV with the mutant fHbp (P = 0.003). By adsorption, the bactericidal
      antibodies were shown to be directed at fHbp. In transgenic mice in which human
      fH bound to the wild-type fHbp but not to the R41S fHbp, the NOMV vaccine with
      the mutant fHbp elicited 5-fold higher serum IgG anti-fHbp titers (P = 0.002),
      and 19-fold higher bactericidal titers than the NOMV vaccine with wild-type fHbp
      (P = 0.001). Thus, in mice that differed only by the presence of human fH, the
      respective results with the two vaccines were opposite. The enhanced bactericidal
      activity elicited by the mutant fHbp vaccine in the presence of human fH far
      outweighed the loss of immunogenicity of the mutant protein in wild-type animals.
      Engineering fHbp not to bind to its cognate complement inhibitor, therefore, may
      increase vaccine immunogenicity in humans.

PMID- 22589721
TI  - Vitamin D inhibits human immunodeficiency virus type 1 and Mycobacterium
      tuberculosis infection in macrophages through the induction of autophagy.
AB  - Low vitamin D levels in human immunodeficiency virus type-1 (HIV) infected
      persons are associated with more rapid disease progression and increased risk for
      Mycobacterium tuberculosis infection. We have previously shown that 1alpha,25
      dihydroxycholecalciferol (1,25D3), the active form of vitamin D, inhibits HIV
      replication in human macrophages through the induction of autophagy. In this
      study, we report that physiological concentrations of 1,25D3 induce the
      production of the human cathelicidin microbial peptide (CAMP) and autophagic flux
      in HIV and M. tuberculosis co-infected human macrophages which inhibits
      mycobacterial growth and the replication of HIV. Using RNA interference for
      Beclin-1 and the autophagy-related 5 homologue, combined with the chemical
      inhibitors of autophagic flux, bafilomycin A1, an inhibitor of autophagosome
      lysosome fusion and subsequent acidification, and SID 26681509 an inhibitor of
      the lysosome hydrolase cathepsin L, we show that the 1,25D3-mediated inhibition
      of HIV replication and mycobacterial growth during single infection or dual
      infection is dependent not only upon the induction of autophagy, but also through
      phagosomal maturation. Moreover, through the use of RNA interference for CAMP, we
      demonstrate that cathelicidin is essential for the 1,25D3 induced autophagic flux
      and inhibition of HIV replication and mycobacterial growth. The present findings
      provide a biological explanation for the benefits and importance of vitamin D
      sufficiency in HIV and M. tuberculosis-infected persons, and provide new insights
      into novel approaches to prevent and treat HIV infection and related
      opportunistic infections.

PMID- 22589722
TI  - Epstein-Barr virus-encoded LMP1 interacts with FGD4 to activate Cdc42 and thereby
      promote migration of nasopharyngeal carcinoma cells.
AB  - Epstein-Barr virus (EBV) is closely associated with nasopharyngeal carcinoma
      (NPC), a human malignancy notorious for its highly metastatic nature. Among EBV
      encoded genes, latent membrane protein 1 (LMP1) is expressed in most NPC tissues
      and exerts oncogenicity by engaging multiple signaling pathways in a ligand
      independent manner. LMP1 expression also results in actin cytoskeleton
      reorganization, which modulates cell morphology and cell motility- cellular
      process regulated by RhoGTPases, such as Cdc42. Despite the prominent association
      of Cdc42 activation with tumorigenesis, the molecular basis of Cdc42 activation
      by LMP1 in NPC cells remains to be elucidated. Here using GST-CBD (active Cdc42
      binding domain) as bait in GST pull-down assays to precipitate active Cdc42 from
      cell lysates, we demonstrated that LMP1 acts through its transmembrane domains to
      preferentially induce Cdc42 activation in various types of epithelial cells,
      including NPC cells. Using RNA interference combined with re-introduction
      experiments, we identified FGD4 (FYVE, RhoGEF and PH domain containing 4) as the
      GEF (guanine nucleotide exchange factor) responsible for the activation of Cdc42
      by LMP1. Serial deletion experiments and co-immunoprecipitation assays further
      revealed that ectopically expressed FGD4 modulated LMP1-mediated Cdc42 activation
      by interacting with LMP1. Moreover, LMP1, through its transmembrane domains,
      directly bound FGD4 and enhanced FGD4 activity toward Cdc42, leading to actin
      cytoskeleton rearrangement and increased motility of NPC cells. Depletion of FGD4
      or Cdc42 significantly reduced (~50%) the LMP1-stimulated cell motility, an
      effect that was partially reversed by expression of a constitutively active
      mutant of Cdc42. Finally, quantitative RT-PCR and immunohistochemistry analyses
      showed that FGD4 and LMP1 were expressed in NPC tissues, supporting the potential
      physiologically relevance of this mechanism in NPC. Collectively, our results not
      only uncover a novel mechanism underlying LMP1-mediated Cdc42 activation, namely
      LMP1 interaction with FGD4, but also functionally link FGD4 to NPC tumorigenesis.

PMID- 22589723
TI  - Nitazoxanide stimulates autophagy and inhibits mTORC1 signaling and intracellular
      proliferation of Mycobacterium tuberculosis.
AB  - Tuberculosis, caused by Mycobacterium tuberculosis infection, is a major cause of
      morbidity and mortality in the world today. M. tuberculosis hijacks the phagosome
      lysosome trafficking pathway to escape clearance from infected macrophages. There
      is increasing evidence that manipulation of autophagy, a regulated catabolic
      trafficking pathway, can enhance killing of M. tuberculosis. Therefore,
      pharmacological agents that induce autophagy could be important in combating
      tuberculosis. We report that the antiprotozoal drug nitazoxanide and its active
      metabolite tizoxanide strongly stimulate autophagy and inhibit signaling by
      mTORC1, a major negative regulator of autophagy. Analysis of 16 nitazoxanide
      analogues reveals similar strict structural requirements for activity in
      autophagosome induction, EGFP-LC3 processing and mTORC1 inhibition. Nitazoxanide
      can inhibit M. tuberculosis proliferation in vitro. Here we show that it inhibits
      M. tuberculosis proliferation more potently in infected human THP-1 cells and
      peripheral monocytes. We identify the human quinone oxidoreductase NQO1 as a
      nitazoxanide target and propose, based on experiments with cells expressing NQO1
      or not, that NQO1 inhibition is partly responsible for mTORC1 inhibition and
      enhanced autophagy. The dual action of nitazoxanide on both the bacterium and the
      host cell response to infection may lead to improved tuberculosis treatment.

PMID- 22589724
TI  - Age of the association between Helicobacter pylori and man.
AB  - When modern humans left Africa ca. 60,000 years ago (60 kya), they were already
      infected with Helicobacter pylori, and these bacteria have subsequently
      diversified in parallel with their human hosts. But how long were humans infected
      by H. pylori prior to the out-of-Africa event? Did this co-evolution predate the
      emergence of modern humans, spanning the species divide? To answer these
      questions, we investigated the diversity of H. pylori in Africa, where both
      humans and H. pylori originated. Three distinct H. pylori populations are native
      to Africa: hpNEAfrica in Afro-Asiatic and Nilo-Saharan speakers, hpAfrica1 in
      Niger-Congo speakers and hpAfrica2 in South Africa. Rather than representing a
      sustained co-evolution over millions of years, we find that the coalescent for
      all H. pylori plus its closest relative H. acinonychis dates to 88-116 kya. At
      that time the phylogeny split into two primary super-lineages, one of which is
      associated with the former hunter-gatherers in southern Africa known as the San.
      H. acinonychis, which infects large felines, resulted from a later host jump from
      the San, 43-56 kya. These dating estimates, together with striking phylogenetic
      and quantitative human-bacterial similarities show that H. pylori is
      approximately as old as are anatomically modern humans. They also suggest that H.
      pylori may have been acquired via a single host jump from an unknown, non-human
      host. We also find evidence for a second Out of Africa migration in the last
      52,000 years, because hpEurope is a hybrid population between hpAsia2 and
      hpNEAfrica, the latter of which arose in northeast Africa 36-52 kya, after the
      Out of Africa migrations around 60 kya.

PMID- 22589725
TI  - Synchronized retrovirus fusion in cells expressing alternative receptor isoforms
      releases the viral core into distinct sub-cellular compartments.
AB  - Disparate enveloped viruses initiate infection by fusing with endosomes. However,
      the highly diverse and dynamic nature of endosomes impairs mechanistic studies of
      fusion and identification of sub-cellular sites supporting the nucleocapsid
      release. We took advantage of the extreme stability of avian retrovirus-receptor
      complexes at neutral pH and of acid-dependence of virus-endosome fusion to
      isolate the latter step from preceding asynchronous internalization/trafficking
      steps. Viruses were trapped within endosomes in the presence of NH4Cl. Removal of
      NH4Cl resulted in a quick and uniform acidification of all subcellular
      compartments, thereby initiating synchronous viral fusion. Single virus imaging
      demonstrated that fusion was initiated within seconds after acidification and
      often culminated in the release of the viral core from an endosome. Comparative
      studies of cells expressing either the transmembrane or GPI-anchored receptor
      isoform revealed that the transmembrane receptor delivered the virus to more
      fusion-permissive compartments. Thus the identity of endosomal compartments, in
      addition to their acidity, appears to modulate viral fusion. A more striking
      manifestation of the virus delivery to distinct compartments in the presence of
      NH4Cl was the viral core release into the cytosol of cells expressing the
      transmembrane receptor and into endosomes of cells expressing the GPI-anchored
      isoform. In the latter cells, the newly released cores exhibited restricted
      mobility and were exposed to a more acidic environment than the cytoplasm. These
      cores appear to enter into the cytosol after an additional slow temperature
      dependent step. We conclude that the NH4Cl block traps the virus within
      intralumenal vesicles of late endosomes in cells expressing the GPI-anchored
      receptor. Viruses surrounded by more than one endosomal membrane release their
      core into the cytoplasm in two steps--fusion with an intralumenal vesicle
      followed by a yet unknown temperature-dependent step that liberates the core from
      late endosomes.

PMID- 22589727
TI  - 2'-O methylation of the viral mRNA cap by West Nile virus evades ifit1-dependent
      and -independent mechanisms of host restriction in vivo.
AB  - Prior studies have shown that 2'-O methyltransferase activity of flaviviruses,
      coronaviruses, and poxviruses promotes viral evasion of Ifit1, an interferon
      stimulated innate immune effector protein. Viruses lacking 2'-O methyltransferase
      activity exhibited attenuation in primary macrophages that was rescued in cells
      lacking Ifit1 gene expression. Here, we examined the role of Ifit1 in restricting
      pathogenesis in vivo of wild type WNV (WNV-WT) and a mutant in the NS5 gene (WNV
      E218A) lacking 2'-O methylation of the 5' viral RNA cap. While deletion of Ifit1
      had marginal effects on WNV-WT pathogenesis, WNV-E218A showed increased
      replication in peripheral tissues of Ifit1-/- mice after subcutaneous infection,
      yet this failed to correlate with enhanced infection in the brain or lethality.
      In comparison, WNV-E218A was virulent after intracranial infection as judged by
      increased infection in different regions of the central nervous system (CNS) and
      a greater than 16,000-fold decrease in LD(50) values in Ifit1-/- compared to wild
      type mice. Ex vivo infection experiments revealed cell-type specific differences
      in the ability of an Ifit1 deficiency to complement the replication defect of WNV
      E218A. In particular, WNV-E218A infection was impaired in both wild type and
      Ifit1-/- brain microvascular endothelial cells, which are believed to participate
      in blood-brain barrier (BBB) regulation of virus entry into the CNS. A deficiency
      of Ifit1 also was associated with increased neuronal death in vivo, which was
      both cell-intrinsic and mediated by immunopathogenic CD8+ T cells. Our results
      suggest that virulent strains of WNV have largely evaded the antiviral effects of
      Ifit1, and viral mutants lacking 2'-O methylation are controlled in vivo by Ifit1
      dependent and -independent mechanisms in different cell types.

PMID- 22589726
TI  - Epstein-Barr virus infection of naive B cells in vitro frequently selects clones
      with mutated immunoglobulin genotypes: implications for virus biology.
AB  - Epstein-Barr virus (EBV), a lymphomagenic human herpesvirus, colonises the host
      through polyclonal B cell-growth-transforming infections yet establishes
      persistence only in IgD+ CD27+ non-switched memory (NSM) and IgD- CD27+ switched
      memory (SM) B cells, not in IgD+ CD27- naive (N) cells. How this selectivity is
      achieved remains poorly understood. Here we show that purified N, NSM and SM cell
      preparations are equally transformable in vitro to lymphoblastoid cells lines
      (LCLs) that, despite upregulating the activation-induced cytidine deaminase (AID)
      enzyme necessary for Ig isotype switching and Ig gene hypermutation, still retain
      the surface Ig phenotype of their parental cells. However, both N- and NSM
      derived lines remain inducible to Ig isotype switching by surrogate T cell
      signals. More importantly, IgH gene analysis of N cell infections revealed two
      features quite distinct from parallel mitogen-activated cultures. Firstly,
      following 4 weeks of EBV-driven polyclonal proliferation, individual clonotypes
      then become increasingly dominant; secondly, in around 35% cases these clonotypes
      carry Ig gene mutations which both resemble AID products and, when analysed in
      prospectively-harvested cultures, appear to have arisen by sequence
      diversification in vitro. Thus EBV infection per se can drive at least some naive
      B cells to acquire Ig memory genotypes; furthermore, such cells are often
      favoured during an LCL's evolution to monoclonality. Extrapolating to viral
      infections in vivo, these findings could help to explain how EBV-infected cells
      become restricted to memory B cell subsets and why EBV-driven lymphoproliferative
      lesions, in primary infection and/or immunocompromised settings, so frequently
      involve clones with memory genotypes.

PMID- 22589728
TI  - Negative selection by an endogenous retrovirus promotes a higher-avidity CD4+ T
      cell response to retroviral infection.
AB  - Effective T cell responses can decisively influence the outcome of retroviral
      infection. However, what constitutes protective T cell responses or determines
      the ability of the host to mount such responses is incompletely understood. Here
      we studied the requirements for development and induction of CD4+ T cells that
      were essential for immunity to Friend virus (FV) infection of mice, according to
      their TCR avidity for an FV-derived epitope. We showed that a self peptide,
      encoded by an endogenous retrovirus, negatively selected a significant fraction
      of polyclonal FV-specific CD4+ T cells and diminished the response to FV
      infection. Surprisingly, however, CD4+ T cell-mediated antiviral activity was
      fully preserved. Detailed repertoire analysis revealed that clones with low
      avidity for FV-derived peptides were more cross-reactive with self peptides and
      were consequently preferentially deleted. Negative selection of low-avidity FV
      reactive CD4+ T cells was responsible for the dominance of high-avidity clones in
      the response to FV infection, suggesting that protection against the primary
      infecting virus was mediated exclusively by high-avidity CD4+ T cells. Thus,
      although negative selection reduced the size and cross-reactivity of the
      available FV-reactive naive CD4+ T cell repertoire, it increased the overall
      avidity of the repertoire that responded to infection. These findings demonstrate
      that self proteins expressed by replication-defective endogenous retroviruses can
      heavily influence the formation of the TCR repertoire reactive with exogenous
      retroviruses and determine the avidity of the response to retroviral infection.
      Given the overabundance of endogenous retroviruses in the human genome, these
      findings also suggest that endogenous retroviral proteins, presented by products
      of highly polymorphic HLA alleles, may shape the human TCR repertoire that reacts
      with exogenous retroviruses or other infecting pathogens, leading to
      interindividual heterogeneity.

PMID- 22589729
TI  - Large-scale gene disruption in Magnaporthe oryzae identifies MC69, a secreted
      protein required for infection by monocot and dicot fungal pathogens.
AB  - To search for virulence effector genes of the rice blast fungus, Magnaporthe
      oryzae, we carried out a large-scale targeted disruption of genes for 78 putative
      secreted proteins that are expressed during the early stages of infection of M.
      oryzae. Disruption of the majority of genes did not affect growth, conidiation,
      or pathogenicity of M. oryzae. One exception was the gene MC69. The mc69 mutant
      showed a severe reduction in blast symptoms on rice and barley, indicating the
      importance of MC69 for pathogenicity of M. oryzae. The mc69 mutant did not
      exhibit changes in saprophytic growth and conidiation. Microscopic analysis of
      infection behavior in the mc69 mutant revealed that MC69 is dispensable for
      appressorium formation. However, mc69 mutant failed to develop invasive hyphae
      after appressorium formation in rice leaf sheath, indicating a critical role of
      MC69 in interaction with host plants. MC69 encodes a hypothetical 54 amino acids
      protein with a signal peptide. Live-cell imaging suggested that fluorescently
      labeled MC69 was not translocated into rice cytoplasm. Site-directed mutagenesis
      of two conserved cysteine residues (Cys36 and Cys46) in the mature MC69 impaired
      function of MC69 without affecting its secretion, suggesting the importance of
      the disulfide bond in MC69 pathogenicity function. Furthermore, deletion of the
      MC69 orthologous gene reduced pathogenicity of the cucumber anthracnose fungus
      Colletotrichum orbiculare on both cucumber and Nicotiana benthamiana leaves. We
      conclude that MC69 is a secreted pathogenicity protein commonly required for
      infection of two different plant pathogenic fungi, M. oryzae and C. orbiculare
      pathogenic on monocot and dicot plants, respectively.

PMID- 22589730
TI  - Repeated, selection-driven genome reduction of accessory genes in experimental
      populations.
AB  - Genome reduction has been observed in many bacterial lineages that have adapted
      to specialized environments. The extreme genome degradation seen for obligate
      pathogens and symbionts appears to be dominated by genetic drift. In contrast,
      for free-living organisms with reduced genomes, the dominant force is proposed to
      be direct selection for smaller, streamlined genomes. Most variation in gene
      content for these free-living species is of "accessory" genes, which are commonly
      gained as large chromosomal islands that are adaptive for specialized traits such
      as pathogenicity. It is generally unclear, however, whether the process of
      accessory gene loss is largely driven by drift or selection. Here we demonstrate
      that selection for gene loss, and not a shortened genome, per se, drove massive,
      rapid reduction of accessory genes. In just 1,500 generations of experimental
      evolution, 80% of populations of Methylobacterium extorquens AM1 experienced
      nearly parallel deletions removing up to 10% of the genome from a megaplasmid
      present in this strain. The absence of these deletion events in a mutation
      accumulation experiment suggested that selection, rather than drift, has
      dominated the process. Reconstructing these deletions confirmed that they were
      beneficial in their selective regimes, but led to decreased performance in
      alternative environments. These results indicate that selection can be crucial in
      eliminating unnecessary genes during the early stages of adaptation to a
      specialized environment.

PMID- 22589731
TI  - Identification of genes that promote or antagonize somatic homolog pairing using
      a high-throughput FISH-based screen.
AB  - The pairing of homologous chromosomes is a fundamental feature of the meiotic
      cell. In addition, a number of species exhibit homolog pairing in nonmeiotic,
      somatic cells as well, with evidence for its impact on both gene regulation and
      double-strand break (DSB) repair. An extreme example of somatic pairing can be
      observed in Drosophila melanogaster, where homologous chromosomes remain aligned
      throughout most of development. However, our understanding of the mechanism of
      somatic homolog pairing remains unclear, as only a few genes have been implicated
      in this process. In this study, we introduce a novel high-throughput fluorescent
      in situ hybridization (FISH) technology that enabled us to conduct a genome-wide
      RNAi screen for factors involved in the robust somatic pairing observed in
      Drosophila. We identified both candidate "pairing promoting genes" and candidate
      "anti-pairing genes," providing evidence that pairing is a dynamic process that
      can be both enhanced and antagonized. Many of the genes found to be important for
      promoting pairing are highly enriched for functions associated with mitotic cell
      division, suggesting a genetic framework for a long-standing link between
      chromosome dynamics during mitosis and nuclear organization during interphase. In
      contrast, several of the candidate anti-pairing genes have known interphase
      functions associated with S-phase progression, DNA replication, and chromatin
      compaction, including several components of the condensin II complex. In
      combination with a variety of secondary assays, these results provide insights
      into the mechanism and dynamics of somatic pairing.

PMID- 22589732
TI  - Hypersensitive to red and blue 1 and its modification by protein phosphatase 7
      are implicated in the control of Arabidopsis stomatal aperture.
AB  - The stomatal pores are located on the plant leaf epidermis and regulate CO(2)
      uptake for photosynthesis and the loss of water by transpiration. Their stomatal
      aperture therefore affects photosynthesis, water use efficiency, and agricultural
      crop yields. Blue light, one of the environmental signals that regulates the
      plant stomatal aperture, is perceived by the blue/UV-A light-absorbing
      cryptochromes and phototropins. The signal transduction cascades that link the
      perception of light to the stomatal opening response are still largely unknown.
      Here, we report two new players, Hypersensitive to Red and Blue 1 (HRB1) and
      Protein Phosphatase 7 (PP7), and their genetic and biochemical interactions in
      the control of stomatal aperture. Mutations in either HRB1 or PP7 lead to the
      misregulation of the stomatal aperture and reduce water loss under blue light.
      Both HRB1 and PP7 are expressed in the guard cells in response to a light-to-dark
      or dark-to-light transition. HRB1 interacts with PP7 through its N-terminal ZZ
      type zinc finger motif and requires a functional PP7 for its stomatal opening
      response. HRB1 is phosphorylated in vivo, and PP7 can dephosphorylate HRB1. HRB1
      is mostly dephosphorylated in a protein complex of 193 kDa in the dark, and blue
      light increases complex size to 285 kDa. In the pp7 mutant, this size shift is
      impaired, and HRB1 is predominately phosphorylated. We propose that a
      modification of HRB1 by PP7 under blue light is essential to acquire a proper
      conformation or to bring in new components for the assembly of a functional HRB1
      protein complex. Guard cells control stomatal opening in response to multiple
      environmental or biotic stimuli. This study may furnish strategies that allow
      plants to enjoy the advantages of both constitutive and ABA-induced protection
      under water-limiting conditions.

PMID- 22589733
TI  - Functional centromeres determine the activation time of pericentric origins of
      DNA replication in Saccharomyces cerevisiae.
AB  - The centromeric regions of all Saccharomyces cerevisiae chromosomes are found in
      early replicating domains, a property conserved among centromeres in fungi and
      some higher eukaryotes. Surprisingly, little is known about the biological
      significance or the mechanism of early centromere replication; however, the
      extensive conservation suggests that it is important for chromosome maintenance.
      Do centromeres ensure their early replication by promoting early activation of
      nearby origins, or have they migrated over evolutionary time to reside in early
      replicating regions? In Candida albicans, a neocentromere contains an early
      firing origin, supporting the first hypothesis but not addressing whether the new
      origin is intrinsically early firing or whether the centromere influences
      replication time. Because the activation time of individual origins is not an
      intrinsic property of S. cerevisiae origins, but is influenced by surrounding
      sequences, we sought to test the hypothesis that centromeres influence
      replication time by moving a centromere to a late replication domain. We used a
      modified Meselson-Stahl density transfer assay to measure the kinetics of
      replication for regions of chromosome XIV in which either the functional
      centromere or a point-mutated version had been moved near origins that reside in
      a late replication region. We show that a functional centromere acts in cis over
      a distance as great as 19 kb to advance the initiation time of origins. Our
      results constitute a direct link between establishment of the kinetochore and the
      replication initiation machinery, and suggest that the proposed higher-order
      structure of the pericentric chromatin influences replication initiation.

PMID- 22589734
TI  - Genome-wide copy number analysis uncovers a new HSCR gene: NRG3.
AB  - Hirschsprung disease (HSCR) is a congenital disorder characterized by
      aganglionosis of the distal intestine. To assess the contribution of copy number
      variants (CNVs) to HSCR, we analysed the data generated from our previous genome
      wide association study on HSCR patients, whereby we identified NRG1 as a new HSCR
      susceptibility locus. Analysis of 129 Chinese patients and 331 ethnically matched
      controls showed that HSCR patients have a greater burden of rare CNVs (p = 1.50 *
      10(-5)), particularly for those encompassing genes (p = 5.00 * 10(-6)). Our study
      identified 246 rare-genic CNVs exclusive to patients. Among those, we detected a
      NRG3 deletion (p = 1.64 * 10(-3)). Subsequent follow-up (96 additional patients
      and 220 controls) on NRG3 revealed 9 deletions (combined p = 3.36 * 10(-5)) and 2
      de novo duplications among patients and two deletions among controls.
      Importantly, NRG3 is a paralog of NRG1. Stratification of patients by
      presence/absence of HSCR-associated syndromes showed that while syndromic-HSCR
      patients carried significantly longer CNVs than the non-syndromic or controls (p
      = 1.50 * 10(-5)), non-syndromic patients were enriched in CNV number when
      compared to controls (p = 4.00 * 10(-6)) or the syndromic counterpart. Our
      results suggest a role for NRG3 in HSCR etiology and provide insights into the
      relative contribution of structural variants in both syndromic and non-syndromic
      HSCR. This would be the first genome-wide catalog of copy number variants
      identified in HSCR.

PMID- 22589735
TI  - Congenital heart disease-causing Gata4 mutation displays functional deficits in
      vivo.
AB  - Defects of atrial and ventricular septation are the most frequent form of
      congenital heart disease, accounting for almost 50% of all cases. We previously
      reported that a heterozygous G296S missense mutation of GATA4 caused atrial and
      ventricular septal defects and pulmonary valve stenosis in humans. GATA4 encodes
      a cardiac transcription factor, and when deleted in mice it results in cardiac
      bifida and lethality by embryonic day (E)9.5. In vitro, the mutant GATA4 protein
      has a reduced DNA binding affinity and transcriptional activity and abolishes a
      physical interaction with TBX5, a transcription factor critical for normal heart
      formation. To characterize the mutation in vivo, we generated mice harboring the
      same mutation, Gata4 G295S. Mice homozygous for the Gata4 G295S mutant allele
      have normal ventral body patterning and heart looping, but have a thin
      ventricular myocardium, single ventricular chamber, and lethality by E11.5. While
      heterozygous Gata4 G295S mutant mice are viable, a subset of these mice have
      semilunar valve stenosis and small defects of the atrial septum. Gene expression
      studies of homozygous mutant mice suggest the G295S protein can sufficiently
      activate downstream targets of Gata4 in the endoderm but not in the developing
      heart. Cardiomyocyte proliferation deficits and decreased cardiac expression of
      CCND2, a member of the cyclin family and a direct target of Gata4, were found in
      embryos both homozygous and heterozygous for the Gata4 G295S allele. To further
      define functions of the Gata4 G295S mutation in vivo, compound mutant mice were
      generated in which specific cell lineages harbored both the Gata4 G295S mutant
      and Gata4 null alleles. Examination of these mice demonstrated that the Gata4
      G295S protein has functional deficits in early myocardial development. In
      summary, the Gata4 G295S mutation functions as a hypomorph in vivo and leads to
      defects in cardiomyocyte proliferation during embryogenesis, which may contribute
      to the development of congenital heart defects in humans.

PMID- 22589736
TI  - Histone h1 depletion impairs embryonic stem cell differentiation.
AB  - Pluripotent embryonic stem cells (ESCs) are known to possess a relatively open
      chromatin structure; yet, despite efforts to characterize the chromatin
      signatures of ESCs, the role of chromatin compaction in stem cell fate and
      function remains elusive. Linker histone H1 is important for higher-order
      chromatin folding and is essential for mammalian embryogenesis. To investigate
      the role of H1 and chromatin compaction in stem cell pluripotency and
      differentiation, we examine the differentiation of embryonic stem cells that are
      depleted of multiple H1 subtypes. H1c/H1d/H1e triple null ESCs are more resistant
      to spontaneous differentiation in adherent monolayer culture upon removal of
      leukemia inhibitory factor. Similarly, the majority of the triple-H1 null
      embryoid bodies (EBs) lack morphological structures representing the three germ
      layers and retain gene expression signatures characteristic of undifferentiated
      ESCs. Furthermore, upon neural differentiation of EBs, triple-H1 null cell
      cultures are deficient in neurite outgrowth and lack efficient activation of
      neural markers. Finally, we discover that triple-H1 null embryos and EBs fail to
      fully repress the expression of the pluripotency genes in comparison with wild
      type controls and that H1 depletion impairs DNA methylation and changes of
      histone marks at promoter regions necessary for efficiently silencing
      pluripotency gene Oct4 during stem cell differentiation and embryogenesis. In
      summary, we demonstrate that H1 plays a critical role in pluripotent stem cell
      differentiation, and our results suggest that H1 and chromatin compaction may
      mediate pluripotent stem cell differentiation through epigenetic repression of
      the pluripotency genes.

PMID- 22589737
TI  - ELK1 uses different DNA binding modes to regulate functionally distinct classes
      of target genes.
AB  - Eukaryotic transcription factors are grouped into families and, due to their
      similar DNA binding domains, often have the potential to bind to the same genomic
      regions. This can lead to redundancy at the level of DNA binding, and mechanisms
      are required to generate specific functional outcomes that enable distinct gene
      expression programmes to be controlled by a particular transcription factor. Here
      we used ChIP-seq to uncover two distinct binding modes for the ETS transcription
      factor ELK1. In one mode, other ETS transcription factors can bind regulatory
      regions in a redundant fashion; in the second, ELK1 binds in a unique fashion to
      another set of genomic targets. Each binding mode is associated with different
      binding site features and also distinct regulatory outcomes. Furthermore, the
      type of binding mode also determines the control of functionally distinct
      subclasses of genes and hence the phenotypic response elicited. This is
      demonstrated for the unique binding mode where a novel role for ELK1 in
      controlling cell migration is revealed. We have therefore uncovered an unexpected
      link between the type of binding mode employed by a transcription factor, the
      subsequent gene regulatory mechanisms used, and the functional categories of
      target genes controlled.

PMID- 22589739
TI  - Acquisition order of Ras and p53 gene alterations defines distinct adrenocortical
      tumor phenotypes.
AB  - Sporadic adrenocortical carcinomas (ACC) are rare endocrine neoplasms with a
      dismal prognosis. By contrast, benign tumors of the adrenal cortex are common in
      the general population. Whether benign tumors represent a separate entity or are
      in fact part of a process of tumor progression ultimately leading to an ACC is
      still an unresolved issue. To this end, we have developed a mouse model of tumor
      progression by successively transducing genes altered in adrenocortical tumors
      into normal adrenocortical cells. The introduction in different orders of the
      oncogenic allele of Ras (H-Ras(G12V)) and the mutant p53(DD) that disrupts the
      p53 pathway yielded tumors displaying major differences in histological features,
      tumorigenicity, and metastatic behavior. Whereas the successive expression of
      Ras(G12V) and p53(DD) led to highly malignant tumors with metastatic behavior,
      reminiscent of those formed after the simultaneous introduction of p53(DD) and
      Ras(G12V), the reverse sequence gave rise only to benign tumors. Microarray
      profiling revealed that 157 genes related to cancer development and progression
      were differentially expressed. Of these genes, 40 were up-regulated and 117 were
      down-regulated in malignant cell populations as compared with benign cell
      populations. This is the first evidence-based observation that ACC development
      follows a multistage progression and that the tumor phenotype is directly
      influenced by the order of acquisition of genetic alterations.

PMID- 22589740
TI  - New insight into the history of domesticated apple: secondary contribution of the
      European wild apple to the genome of cultivated varieties.
AB  - The apple is the most common and culturally important fruit crop of temperate
      areas. The elucidation of its origin and domestication history is therefore of
      great interest. The wild Central Asian species Malus sieversii has previously
      been identified as the main contributor to the genome of the cultivated apple
      (Malus domestica), on the basis of morphological, molecular, and historical
      evidence. The possible contribution of other wild species present along the Silk
      Route running from Asia to Western Europe remains a matter of debate,
      particularly with respect to the contribution of the European wild apple. We used
      microsatellite markers and an unprecedented large sampling of five Malus species
      throughout Eurasia (839 accessions from China to Spain) to show that multiple
      species have contributed to the genetic makeup of domesticated apples. The wild
      European crabapple M. sylvestris, in particular, was a major secondary
      contributor. Bidirectional gene flow between the domesticated apple and the
      European crabapple resulted in the current M. domestica being genetically more
      closely related to this species than to its Central Asian progenitor, M.
      sieversii. We found no evidence of a domestication bottleneck or clonal
      population structure in apples, despite the use of vegetative propagation by
      grafting. We show that the evolution of domesticated apples occurred over a long
      time period and involved more than one wild species. Our results support the view
      that self-incompatibility, a long lifespan, and cultural practices such as
      selection from open-pollinated seeds have facilitated introgression from wild
      relatives and the maintenance of genetic variation during domestication. This
      combination of processes may account for the diversification of several long
      lived perennial crops, yielding domestication patterns different from those
      observed for annual species.

PMID- 22589743
TI  - Loss of Gnas imprinting differentially affects REM/NREM sleep and cognition in
      mice.
AB  - It has been suggested that imprinted genes are important in the regulation of
      sleep. However, the fundamental question of whether genomic imprinting has a role
      in sleep has remained elusive up to now. In this work we show that REM and NREM
      sleep states are differentially modulated by the maternally expressed imprinted
      gene Gnas. In particular, in mice with loss of imprinting of Gnas, NREM and
      complex cognitive processes are enhanced while REM and REM-linked behaviors are
      inhibited. This is the first demonstration that a specific overexpression of an
      imprinted gene affects sleep states and related complex behavioral traits.
      Furthermore, in parallel to the Gnas overexpression, we have observed an
      overexpression of Ucp1 in interscapular brown adipose tissue (BAT) and a
      significant increase in thermoregulation that may account for the REM/NREM sleep
      phenotypes. We conclude that there must be significant evolutionary advantages in
      the monoallelic expression of Gnas for REM sleep and for the consolidation of REM
      dependent memories. Conversely, biallelic expression of Gnas reinforces slow wave
      activity in NREM sleep, and this results in a reduction of uncertainty in
      temporal decision-making processes.

PMID- 22589742
TI  - Genome-wide association of pericardial fat identifies a unique locus for ectopic
      fat.
AB  - Pericardial fat is a localized fat depot associated with coronary artery calcium
      and myocardial infarction. We hypothesized that genetic loci would be associated
      with pericardial fat independent of other body fat depots. Pericardial fat was
      quantified in 5,487 individuals of European ancestry from the Framingham Heart
      Study (FHS) and the Multi-Ethnic Study of Atherosclerosis (MESA). Genotyping was
      performed using standard arrays and imputed to ~2.5 million Hapmap SNPs. Each
      study performed a genome-wide association analysis of pericardial fat adjusted
      for age, sex, weight, and height. A weighted z-score meta-analysis was conducted,
      and validation was obtained in an additional 3,602 multi-ethnic individuals from
      the MESA study. We identified a genome-wide significant signal in our primary
      meta-analysis at rs10198628 near TRIB2 (MAF 0.49, p = 2.7 * 10(-08)). This SNP
      was not associated with visceral fat (p = 0.17) or body mass index (p = 0.38),
      although we observed direction-consistent, nominal significance with visceral fat
      adjusted for BMI (p = 0.01) in the Framingham Heart Study. Our findings were
      robust among African ancestry (n = 1,442, p = 0.001), Hispanic (n = 1,399, p =
      0.004), and Chinese (n = 761, p = 0.007) participants from the MESA study, with a
      combined p-value of 5.4E-14. We observed TRIB2 gene expression in the pericardial
      fat of mice. rs10198628 near TRIB2 is associated with pericardial fat but not
      measures of generalized or visceral adiposity, reinforcing the concept that there
      are unique genetic underpinnings to ectopic fat distribution.

PMID- 22589741
TI  - Extent, causes, and consequences of small RNA expression variation in human
      adipose tissue.
AB  - Small RNAs are functional molecules that modulate mRNA transcripts and have been
      implicated in the aetiology of several common diseases. However, little is known
      about the extent of their variability within the human population. Here, we
      characterise the extent, causes, and effects of naturally occurring variation in
      expression and sequence of small RNAs from adipose tissue in relation to
      genotype, gene expression, and metabolic traits in the MuTHER reference cohort.
      We profiled the expression of 15 to 30 base pair RNA molecules in subcutaneous
      adipose tissue from 131 individuals using high-throughput sequencing, and
      quantified levels of 591 microRNAs and small nucleolar RNAs. We identified three
      genetic variants and three RNA editing events. Highly expressed small RNAs are
      more conserved within mammals than average, as are those with highly variable
      expression. We identified 14 genetic loci significantly associated with nearby
      small RNA expression levels, seven of which also regulate an mRNA transcript
      level in the same region. In addition, these loci are enriched for variants
      significant in genome-wide association studies for body mass index. Contrary to
      expectation, we found no evidence for negative correlation between expression
      level of a microRNA and its target mRNAs. Trunk fat mass, body mass index, and
      fasting insulin were associated with more than twenty small RNA expression levels
      each, while fasting glucose had no significant associations. This study
      highlights the similar genetic complexity and shared genetic control of small RNA
      and mRNA transcripts, and gives a quantitative picture of small RNA expression
      variation in the human population.

PMID- 22589744
TI  - The number of x chromosomes causes sex differences in adiposity in mice.
AB  - Sexual dimorphism in body weight, fat distribution, and metabolic disease has
      been attributed largely to differential effects of male and female gonadal
      hormones. Here, we report that the number of X chromosomes within cells also
      contributes to these sex differences. We employed a unique mouse model, known as
      the "four core genotypes," to distinguish between effects of gonadal sex (testes
      or ovaries) and sex chromosomes (XX or XY). With this model, we produced gonadal
      male and female mice carrying XX or XY sex chromosome complements. Mice were
      gonadectomized to remove the acute effects of gonadal hormones and to uncover
      effects of sex chromosome complement on obesity. Mice with XX sex chromosomes
      (relative to XY), regardless of their type of gonad, had up to 2-fold increased
      adiposity and greater food intake during daylight hours, when mice are normally
      inactive. Mice with two X chromosomes also had accelerated weight gain on a high
      fat diet and developed fatty liver and elevated lipid and insulin levels. Further
      genetic studies with mice carrying XO and XXY chromosome complements revealed
      that the differences between XX and XY mice are attributable to dosage of the X
      chromosome, rather than effects of the Y chromosome. A subset of genes that
      escape X chromosome inactivation exhibited higher expression levels in adipose
      tissue and liver of XX compared to XY mice, and may contribute to the sex
      differences in obesity. Overall, our study is the first to identify sex
      chromosome complement, a factor distinguishing all male and female cells, as a
      cause of sex differences in obesity and metabolism.

PMID- 22589745
TI  - Bmps and id2a act upstream of Twist1 to restrict ectomesenchyme potential of the
      cranial neural crest.
AB  - Cranial neural crest cells (CNCCs) have the remarkable capacity to generate both
      the non-ectomesenchyme derivatives of the peripheral nervous system and the
      ectomesenchyme precursors of the vertebrate head skeleton, yet how these
      divergent lineages are specified is not well understood. Whereas studies in mouse
      have indicated that the Twist1 transcription factor is important for
      ectomesenchyme development, its role and regulation during CNCC lineage decisions
      have remained unclear. Here we show that two Twist1 genes play an essential role
      in promoting ectomesenchyme at the expense of non-ectomesenchyme gene expression
      in zebrafish. Twist1 does so by promoting Fgf signaling, as well as potentially
      directly activating fli1a expression through a conserved ectomesenchyme-specific
      enhancer. We also show that Id2a restricts Twist1 activity to the ectomesenchyme
      lineage, with Bmp activity preferentially inducing id2a expression in non
      ectomesenchyme precursors. We therefore propose that the ventral migration of
      CNCCs away from a source of Bmps in the dorsal ectoderm promotes ectomesenchyme
      development by relieving Id2a-dependent repression of Twist1 function. Together
      our model shows how the integration of Bmp inhibition at its origin and Fgf
      activation along its migratory route would confer temporal and spatial
      specificity to the generation of ectomesenchyme from the neural crest.

PMID- 22589738
TI  - Genome-wide association for abdominal subcutaneous and visceral adipose reveals a
      novel locus for visceral fat in women.
AB  - Body fat distribution, particularly centralized obesity, is associated with
      metabolic risk above and beyond total adiposity. We performed genome-wide
      association of abdominal adipose depots quantified using computed tomography (CT)
      to uncover novel loci for body fat distribution among participants of European
      ancestry. Subcutaneous and visceral fat were quantified in 5,560 women and 4,997
      men from 4 population-based studies. Genome-wide genotyping was performed using
      standard arrays and imputed to ~2.5 million Hapmap SNPs. Each study performed a
      genome-wide association analysis of subcutaneous adipose tissue (SAT), visceral
      adipose tissue (VAT), VAT adjusted for body mass index, and VAT/SAT ratio (a
      metric of the propensity to store fat viscerally as compared to subcutaneously)
      in the overall sample and in women and men separately. A weighted z-score meta
      analysis was conducted. For the VAT/SAT ratio, our most significant p-value was
      rs11118316 at LYPLAL1 gene (p = 3.1 * 10E-09), previously identified in
      association with waist-hip ratio. For SAT, the most significant SNP was in the
      FTO gene (p = 5.9 * 10E-08). Given the known gender differences in body fat
      distribution, we performed sex-specific analyses. Our most significant finding
      was for VAT in women, rs1659258 near THNSL2 (p = 1.6 * 10-08), but not men (p =
      0.75). Validation of this SNP in the GIANT consortium data demonstrated a similar
      sex-specific pattern, with observed significance in women (p = 0.006) but not men
      (p = 0.24) for BMI and waist circumference (p = 0.04 [women], p = 0.49 [men]).
      Finally, we interrogated our data for the 14 recently published loci for body fat
      distribution (measured by waist-hip ratio adjusted for BMI); associations were
      observed at 7 of these loci. In contrast, we observed associations at only 7/32
      loci previously identified in association with BMI; the majority of overlap was
      observed with SAT. Genome-wide association for visceral and subcutaneous fat
      revealed a SNP for VAT in women. More refined phenotypes for body composition and
      fat distribution can detect new loci not previously uncovered in large-scale GWAS
      of anthropometric traits.

PMID- 22589746
TI  - Prdm5 regulates collagen gene transcription by association with RNA polymerase II
      in developing bone.
AB  - PRDM family members are transcriptional regulators involved in tissue specific
      differentiation. PRDM5 has been reported to predominantly repress transcription,
      but a characterization of its molecular functions in a relevant biological
      context is lacking. We demonstrate here that Prdm5 is highly expressed in
      developing bones; and, by genome-wide mapping of Prdm5 occupancy in pre
      osteoblastic cells, we uncover a novel and unique role for Prdm5 in targeting all
      mouse collagen genes as well as several SLRP proteoglycan genes. In particular,
      we show that Prdm5 controls both Collagen I transcription and fibrillogenesis by
      binding inside the Col1a1 gene body and maintaining RNA polymerase II occupancy.
      In vivo, Prdm5 loss results in delayed ossification involving a pronounced
      impairment in the assembly of fibrillar collagens. Collectively, our results
      define a novel role for Prdm5 in sustaining the transcriptional program necessary
      to the proper assembly of osteoblastic extracellular matrix.

PMID- 22589748
TI  - Retraction of articles.
AB  - This article reports the retraction of articles published in Acta
      Crystallographica Section E between 2007 and 2009.

PMID- 22589749
TI  - Ca(5)Zr(3)F(22).
AB  - Single crystals of Ca(5)Zr(3)F(22), penta-calcium trizirconium docosafluoride,
      were obtained unexpectedly by solid-state reaction between CaF(2) and ZrF(4) in
      the presence of AgF. The structure of the title compound is isotypic with that of
      Sr(5)Zr(3)F(22) and can be described as being composed of layers with composition
      [Zr(3)F(20)](8-) made up from two different [ZrF(8)](4-) square anti-prisms (one
      with site symmetry 2) by corner-sharing. The layers extending parallel to the
      (001) plane are further linked by Ca(2+) cations, forming a three-dimensional
      network. Amongst the four crystallographically different Ca(2+) ions, three are
      located on twofold rotation axes. The Ca(2+) ions exhibit coordination numbers
      ranging from 8 to 12, depending on the cut off, with very distorted fluorine
      environments. Two of the Ca(2+) ions occupy inter-stices between the layers
      whereas the other two are located in void spaces of the [Zr(3)F(20)](8-) layer
      and alternate with the two Zr atoms along [010]. The crystal under investigation
      was an inversion twin.

PMID- 22589747
TI  - Neurospora COP9 signalosome integrity plays major roles for hyphal growth,
      conidial development, and circadian function.
AB  - The COP9 signalosome (CSN) is a highly conserved multifunctional complex that has
      two major biochemical roles: cleaving NEDD8 from cullin proteins and maintaining
      the stability of CRL components. We used mutation analysis to confirm that the
      JAMM domain of the CSN-5 subunit is responsible for NEDD8 cleavage from cullin
      proteins in Neurospora crassa. Point mutations of key residues in the metal
      binding motif (EX(n)HXHX(10)D) of the CSN-5 JAMM domain disrupted CSN
      deneddylation activity without interfering with assembly of the CSN complex or
      interactions between CSN and cullin proteins. Surprisingly, CSN-5 with a mutated
      JAMM domain partially rescued the phenotypic defects observed in a csn-5 mutant.
      We found that, even without its deneddylation activity, the CSN can partially
      maintain the stability of the SCF(FWD-1) complex and partially restore the
      degradation of the circadian clock protein FREQUENCY (FRQ) in vivo. Furthermore,
      we showed that CSN containing mutant CSN-5 efficiently prevents degradation of
      the substrate receptors of CRLs. Finally, we found that deletion of the CAND1
      ortholog in N. crassa had little effect on the conidiation circadian rhythm. Our
      results suggest that CSN integrity plays major roles in hyphal growth, conidial
      development, and circadian function in N. crassa.

PMID- 22589750
TI  - Disodium tris-(dioxidomolybdenum) bis-(diarsenate).
AB  - The asymmetric unit of the title compound, Na(2)(MoO(2))(3)(As(2)O(7))(2), is
      composed of two cyclic MoAs(2)O(11) units and an MoO(6) corner-sharing octa
      hedron. The anionic framework can be decomposed into two types of layers, viz.
      MoO(2)As(2)O(7) and Mo(2)As(2)O(14), which use mixed Mo-O-As and As-O-Mo bridges
      to achieve a new three-dimensional structure with two types of large channels in
      which the Na(+) cations are located. Two O atoms are disordered and are located
      in two positions close to their initial positions with occupancy ratios of 0.612
      (17):0.388 (17) and 0.703 (12):0.298 (12).

PMID- 22589751
TI  - Non-centrosymmetric Na(3)Nb(4)As(3)O(19).
AB  - A new non-centrosymmetric compound, tris-odium tetra-niobium triarsenic nona-deca
      oxide, Na(3)Nb(4)As(3)O(19), has been synthesized by a solid-state reaction at
      1123 K. The structure consists of AsO(4) tetra-hedra and NbO(6) octa-hedra
      sharing corners to form a three-dimensional framework containing two types of
      tunnels running along the c axis, in which the sodium ions are located. Na(+)
      cations occupying statistically several sites, respectively, are surrounded by
      seven, six and four O atoms at distances ranging from 2.08 (1) to 2.88 (4) A. The
      title structure is compared with those containing the same groups, viz.M(2)XO(13)
      and M(2)X(2)O(17) (M = transition metal, and X = As or P).

PMID- 22589752
TI  - (3-{[2,6-Bis(1-methyl-eth-yl)phen-yl]imino-kappaN}-1-phenyl-but-1-en-1-olato
      kappaO)-di-methyl-aluminium.
AB  - The mol-ecular structure of the title compound, [Al(CH(3))(2)(C(22)H(26)NO)],
      displays a monomer with the Al(III) atom in a distorted tetra-hedral environment
      defined by two methyl groups and the N and O atoms of the chelating ketiminate
      anion. The O-Al-N bite angle of the chelating ligand is 94.14 (9) degrees . The O
      C-C-C-N backbone of the ligand is nearly coplanar (r.m.s. deviation = 0.029 A)
      and the Al atom deviates significantly from the mean plane by 0.525 (3) A. In the
      crystal, weak inter-molecular C-H?O inter-actions are observed.

PMID- 22589753
TI  - 1-(Ferrocen-1-ylmeth-yl)-3-methyl-imidazol-3-ium hexa-fluorido-phosphate.
AB  - The crystal structure of the title compound, [Fe(C(5)H(5))(C(10)H(12)N(2))]PF(6),
      consists of a ferrocene-1-methyl-(3-methyl-imidazolium) cation and a hexa
      fluorido-phosphate anion. The ferrocenyl rings are skewed by 6.7 (4) degrees 
      from the ideal eclipsed conformation. The inter-planar angle between the plane of
      the substituted cyclo-penta-dienyl ring and that of the imidazole ring is 89.9
      (4) degrees . The crystal packing is stabilized by C-H?F hydrogen bonds.

PMID- 22589754
TI  - Di-MU-chlorido-bis-[aqua-chloridodimethyl-tin(IV)]-1,4,7,10,13-penta-oxacyclo
      penta-decane (1/1).
AB  - The Sn, Cl and water O atoms of the title compound,
      [Sn(2)(CH(3))(4)Cl(4)(H(2)O)(2)].C(10)H(20)O(5), lie on a special position of 2
      site symmetry. The Sn(IV) atom shows cis-C(2)SnCl(2)O trigonal-bipyramidal
      coordination [C-Sn-C = 157.0 (1) degrees ]; however, two [Me(2)SnCl(2)(H(2)O)]
      units are linked by a tin-chlorine bridge [Sn<-Cl = 3.247 (1) A] across a center
      of inversion, generating a dinuclear species, so that the geometry is better
      regarded as a mer-C(2)SnCl(3)O octa-hedron. The crown ether inter-acts through O
      H?O hydrogen with the metal atom through the coordinated water mol-ecules in an
      outer-sphere manner, generating a hydrogen-bonded chain running along [101]. The
      15-crown-5 mol-ecule is disordered over the 2/m site.

PMID- 22589756
TI  - Bis{N-[(diethyl-amino)-dimethyl-sil-yl]anilinido-kappa(2)N,N'}nickel(II).
AB  - The mononuclear Ni(II) amide, [Ni(C(12)H(21)N(2)Si)(2)], has the Ni(II) atom N,N'
      chelated by the N-silylated anilinide ligands. The ligands are arranged cis to
      each other and obey the C(2)-symmetry operation. The two ends of the N-Si-N
      chelating unit exhibit different affinities for the metal atom: the Ni
      N(anilinide) bond length is 1.913 (3) A and Ni-N(amine) is 2.187 (3) A. The four
      coordinate Ni(II) ion demonstrates a distorted tetra-hedral geometry.

PMID- 22589755
TI  - Bis(9-amino-acridinium) bis-(pyridine-2,6-dicarboxyl-ato)zincate(II) trihydrate.
AB  - In the title compound, (C(13)H(11)N(2))(2)[Zn(C(7)H(3)NO(4))(2)].3H(2)O, the
      Zn(II) ion is six-coordinated with the N(4)O(2) donor set being a distorted octa
      hedron through two almost perpendicular (r.m.s. deviation of ligand atoms from
      the mean plane is 0.057 A) tridentate pyridine-2,6-dicarboxyl-ate ligands
      [dihedral angle between the ligands = 86.06 (4) degrees ]. The charge is
      compensated by two 9-amino-acridinium cations protonated on the ring N atom. A
      variety of inter-molecular contacts, such as ion-ion, N-H?O and O-H?O hydrogen
      bonds, and pi-pi stacking [centroid-centroid distances = 3.4907 (9)-4.1128 (8)
      A], between cations and between anions, play important roles in the formation of
      the three-dimensional network.

PMID- 22589758
TI  - Aqua-bis-[2,5-bis-(pyridin-2-yl)-1,3,4-thia-diazole-kappa(2)N(2),N(3)](trifluoro
      methane-sulfonato-kappaO)copper(II) trifluoro-methane-sulfonate.
AB  - 2,5-Bis(pyridin-2-yl)-1,3,4-thia-diazole (denoted L) has been found to act as a
      bidentate ligand in the monomeric title complex,
      [Cu(CF(3)O(3)S)(C(12)H(8)N(4)S)(2)(H(2)O)](CF(3)O(3)S). The complex shows a
      distorted octahedrally coordinated copper(II) cation which is linked to two thia
      diazole ligands, one water mol-ecule and one trifluoro-methane-sulfonate anion.
      The second trifluoro-methane-sulfonate anion does not coordinate the copper(II)
      cation. Each thia-diazole ligand uses one pyridyl and one thia-diazole N atom for
      the coordination of copper. The N atom of the second non-coordinating pyridyl
      substituent is found on the same side of the 1,3,4-thia-diazole ring as the S
      atom. The trifluoro-methane-sulfonate ions are involved in a three-dimensional
      network of O-H?O hydrogen bonds. C-H?N inter-actions also occur.

PMID- 22589757
TI  - [N'-(3-Eth-oxy-2-oxidobenzyl-idene)-4-hy-droxy-3-meth-oxy
      benzohydrazidato](methanol)dioxidomolybdenum(VI).
AB  - In the title dioxidomolybdenum(VI) complex,
      [Mo(C(17)H(16)N(2)O(5))O(2)(CH(3)OH)], the Mo(VI) atom is coordinated by the
      phenolate O, imine N and enolic O atoms of the tridentate hydrazone ligand, one
      methanol O atom, and two oxide O atoms, forming a distorted octa-hedral
      coordination geometry. The oxide O atoms adopt a cis conformation: one is trans
      to the methanol O atom and the other is trans to the ligand N atom. The dihedral
      angle between the two benzene rings in the hydrazone ligand is 4.0 (3) degrees .
      In the crystal, mol-ecules are linked by O-H?N and O-H?O hydrogen bonds.

PMID- 22589759
TI  - Poly[octakis(1H-imidazole-kappaN(3))octa-MU-oxido-tetra-oxidodicopper(II)tetra
      vanadate(V)].
AB  - In the title inorganic-organic hybrid compound,
      [Cu(2)V(4)O(12)(C(3)H(4)N(2))(8)](n), the V(V) ion is tetra-coordinated by four O
      atoms and the Cu(II) ion is hexa-coordinated by four N atoms from four imidazole
      ligands and two O atoms from two tetra-hedral vanadate (VO(4)) units in a
      distorted octa-hedral geometry. The structure consists of two-dimensional sheets
      constructed from centrosymmetric cyclic [V(4)O(12)](4-) anions covalently bound
      through O to [Cu(imidazole)(4)](2+) cations. Adjacent sheets are linked by N-H?O
      hydrogen bonds and weak C-H?pi inter-actions (H?centroid distances = 2.59, 2.66,
      2.76, 2.91 and 2.98 A into a three-dimensional supra-molecular network.

PMID- 22589760
TI  - Tricarbonyl-chlorido(eta(5)-cyclo-penta-dien-yl)molybdenum(II).
AB  - The structure of the title compound, [Mo(C(5)H(5))Cl(CO)(3)], reveals a pseudo
      square-pyramidal piano-stool coordination around the Mo(II) ion, which is
      surrounded by a cyclo-penta-dienyl ring, three carbonyl groups and a chloride
      ligand.

PMID- 22589761
TI  - catena-Poly[[[aqua-manganese(III)]-MU-(E)-5-bromo-N-[2-(5-bromo-2-oxidobenzyl
      idene-amino)-4-nitro-phen-yl]-2-oxidobenzamidato] N,N-dimethyl-fomamide
      monosolvate].
AB  - The asymmetric unit of the title complex,
      {[Mn(C(20)H(10)Br(2)N(3)O(5))(H(2)O)].(CH(3))(2)NCHO}(n), consists of one Mn(III)
      ion, one (E)-5-bromo-N-[2-(5-bromo-2-oxidobenzyl-idene-amino)-4-nitro-phen-yl]-2
      oxidobenzamidate ligand (Schiff base), one water mol-ecule and an N,N-dimethyl
      formamide mol-ecule. The coordination geometry around the Mn(III) ion is a
      distorted octa-hedron, being surrounded by two O and two N atoms from the Schiff
      base, which are positioned in the equatorial plane. The water mol-ecule and the O
      atom of the carbonyl group from the adjacent Mn(III) complex are situated at the
      axial positions, leading to a polymeric chain along the c axis. In the crystal,
      the complex and N,N-dimethyl-formamide mol-ecules are connected via O-H?O, C-H?O
      and C-H?Br hydrogen bonds, forming a three-dimensional network.

PMID- 22589762
TI  - catena-Poly[[dichloridomercury(II)]-N'-nicotinoylnicotinohydrazide].
AB  - The title complex, [HgCl(2)(C(12)H(10)N(4)O(2))](n), is composed of one Hg(II)
      ion, one nnh ligand (nnh = N'-nicotinoylnicotinohydrazide) and two coordinated
      chloride ions. The Hg(II) ion shows a distorted tetra-hedral geometry, being
      surrounded by two N atoms from two nnh ligands and two chloride ions. Due to the
      bridging role of nnh, the Hg(II) atoms are connected into polymeric chains along
      the c axis, which are further inter-linked via N-H?O and C-H?Cl hydrogen-bonding
      inter-actions, forming a three-dimensional network.

PMID- 22589763
TI  - catena-Poly[[diaqua-bis(1H-imidazole-kappaN(3))cobalt(II)]-MU-2,3,5,6-tetra
      chloro-tereph-thal-ato-kappa(2)O(1):O(4)].
AB  - In the title compound, [Co(C(8)Cl(4)O(4))(C(3)H(4)N(2))(2)(H(2)O)(2)](n), the
      Co(II) ion displays a distorted octa-hedral coordination geometry with two O
      atoms from two monodentate tetra-chloro-terephthalate dianions, two N atoms from
      two imidazole mol-ecules and two O atoms from two water mol-ecules. The Co(II)
      ions are connected via the tetra-chloro-terephthalate dianions into a chain
      running along the crystallographic [110] direction. Adjacent chains are linked
      into a two-dimensional network arranged parallel to (010) by classical N-H?O and
      O-H?O hydrogen bonds.

PMID- 22589764
TI  - Bis{1-[(benzo-yloxy)meth-yl]-1H-1,2,3-benzotriazole-kappaN(3)}(nitrato
      kappa(2)O,O')-silver(I).
AB  - In the crystal structure of the title coordination compound,
      [Ag(NO(3))(C(14)H(11)N(3)O(2))(2)], the Ag(I) atom is four-coordinated in a
      distorted tetra-hedral geometry by two O atoms from one nitrate group and two N
      atoms from two different 1-[(benzo-yloxy)meth-yl]-1H-1,2,3-triazole ligands. In
      the complex, the two coordinated benzotriazole rings rings are nearly
      perpendicular, the dihedral angle between their planes being 87.08 (6) degrees .

PMID- 22589765
TI  - Poly[[MU(10)-4,4'-(ethane-1,2-diyldi-oxy)dibenzoato]dipotassium].
AB  - The title salt, [K(2)(C(16)H(12)O(6))](n), was obtained by the reaction of 1,2
      bis-[4-(ethyl-carbox-yl)-phenox-yl]ethane with KOH in water. The anion lies on a
      crystallographic inversion center, which is located at the mid-point of the
      central C-C bond. The K(+) cation is coordinated by six O atoms, two from the
      chelating carboxyl-ate group of the anion and four from four neighboring and
      monodentately binding anions, giving rise to an irregular [KO(6)] coordination
      polyhedron. The coordination mode of the cation leads to the formation of K/O
      layers parallel to (100). These layers are linked by the nearly coplanar anions
      (r.m.s. deviation of 0.064 A of the carboxyl, aryl and O-CH(2) groups from the
      least-squares plane) into a three-dimentional network.

PMID- 22589766
TI  - Bis[MU-N-(3-meth-oxy-2-oxidobenzyl-idene-1:2kappa(2)O(2):O(2))-l-isoleucinato
      2kappa(2)N,O]bis-(1,10-phenanthroline-1kappa(2)N,N')dinickel(II) methanol tetra
      solvate trihydrate.
AB  - In the title complex,
      [Ni(2)(C(14)H(17)NO(4))(2)(C(12)H(8)N(2))(2)].4CH(3)OH.3H(2)O, the two Ni(II)
      ions are bridged by two Schiff base anions, leading to a dinuclear complex. One
      Ni(II) ion is six-coordinated by four O atoms and two N atoms of two tridentate
      Schiff base ligands derived from the condensation of l-isoleucine and o-vanillin.
      The other Ni(II) ion is six-coordinated by four N atoms of two 1,10
      phenanthroline ligands and two O atoms of the Schiff base ligands. In the
      crystal, inter-molecular O-H?O and C-H?O hydrogen bonds lead to a three
      dimensional structure. Intra-molecular C-H?O hydrogen bonds are also present. One
      of the methyl groups of the l-isoleucinate moieties is disordered over two sets
      of sites with an occupancy ratio of 0.687 (19):0.313 (19) and two methanol mol
      ecules are half-occupied.

PMID- 22589767
TI  - Diaqua-bis-(5-carb-oxy-2-ethyl-1H-imidazole-4-carboxyl-ato
      kappa(2)N(3),O(4))cobalt(II) trihydrate.
AB  - In the title compound, [Co(C(7)H(7)N(2)O(4))(2)(H(2)O)(2)].3H(2)O, the Co(II)
      cation, located on an inversion center, is N,O-chelated by two 5-carboxy-2-ethyl
      1H-imidazole-4-carboxylate anions and further coordinated by two water mol-ecules
      in a distorted octa-hedral geometry. Only one carboxy group of the anion is
      deprotonated, and the two carboxyl groups of the same anion are linked via an
      intra-molecular O-H?O hydrogen bond. One of the lattice water mol-ecules is
      located on an inversion center, its H atom equally disordered over two positions.
      One of H atoms of another lattice water mol-ecules is also equally disordered
      over two sites. Water H atoms and the amino H atom all are involved in an inter
      molecular hydrogen-bonded network in the crystal.

PMID- 22589768
TI  - Dichloridotetra-kis-(1H-1,2,4-triazole-kappaN(4))copper(II).
AB  - The central Cu(II) atom of the molecular title complex,
      [CuCl(2)(C(2)H(3)N(3))(4)], is situated on a site with symmetry 2.22. It is six
      coordinated in an elongated octa-hedral geometry, with the equatorial plane
      defined by four N atoms of four 1,2,4-triazole ligands and the axial positions
      occupied by two Cl atoms situated on a twofold axis. The mol-ecules are connected
      via N-H?Cl hydrogen bonds and the crystal consists of two inter-penetrating three
      dimensional hydrogen-bonded frameworks.

PMID- 22589769
TI  - Sodium (1R)-d-glucit-1-yl-sulfonate monohydrate.
AB  - The title salt, Na(+).C(6)H(13)O(9)S(-).H(2)O, crystallizes with three
      independent cations, molecular anions and solvent water molecules in the
      asymmetric unit. This crystalline monohydrate addition product, formed by
      reaction of d-glucose and sodium hydrogen sulfite in water, forms a three
      dimensional network through complex cation coordination and extensive inter
      molecular hydrogen bonding. Each of the independent mol-ecules has an open-chain
      structure with the carbon chains adopting a sickle-like conformation, similar to
      that found in the potassium salt [Cole et al. (2001 ?). Carbohydr. Res.335, 1
      10], but there are significant differences in the patterns of complexation.

PMID- 22589770
TI  - Poly[MU(2)-aqua-bis-[MU(4)-2-(1H-1,2,3-benzotriazol-1-yl)acetato]-dipotassium].
AB  - In the title compound, [K(2)(C(8)H(6)N(3)O(2))(2)(H(2)O)](n), each K(+) ion is
      seven-coordinated by one O atom from a bridging water mol-ecule, five carboxyl
      ate O atoms and one N atom from a benzotriazole group, forming a distorted mono
      capped octa-hedral geometry. In the crystal, the carboxyl-ate groups act as
      bridging ligands, forming a two-dimensional polymer parallel to (001). The aqua
      ligand, which lies on a twofold rotation axis, forms inter-molecular O-H?O
      hydrogen bonds within these layers.

PMID- 22589771
TI  - Dichlorido[2-(phenyl-imino-meth-yl)quinoline-N,N']palladium(II).
AB  - In the title complex, [PdCl(2)(C(16)H(12)N(2))], the Pd(II) ion is coordinated by
      two N atoms [Pd-N 2.039 (2), 2.073 (2) A] from a bidentate ligand and two
      chloride anions [Pd-Cl 2.2655 (7), 2.2991 (7) A] in a distorted square-planar
      geometry. In the crystal, pi-pi inter-actions between the six-membered rings of
      the quinoline fragments [centroid-centroid distances = 3.815 (5), 3.824 (5) A]
      link two mol-ecules into centrosymmetric dimers.

PMID- 22589772
TI  - rac-{[2-(Diphenyl-thio-phosphor-yl)ferrocen-yl]meth-yl}dimethyl-ammonium diphenyl
      dithio-phosphinate.
AB  - 2-(Diphenyl-thio-phosphino)dimethyl-amino-methyl-ferrocene is a key inter-mediate
      in the synthesis of various ferrocenyl ligands. During one such synthesis, the
      title compound, [Fe(C(5)H(5))(C(20)H(22)NPS)](C(12)H(10)PS(2)), was isolated as a
      by-product. It is built up by association of (2-(diphenyl-phosphino)ferrocen
      yl)meth-yl)dimethyl-ammonium cations and diphenyl-phosphino dithio-ate anions. N
      H?S, C-H?S and C-H?pi inter-actions link the anions and cations. Each anion
      cation pair is linked two by two through C-H?pi inter-actions, forming pseudo
      dimers.

PMID- 22589773
TI  - (Carbonato-kappa(2)O,O')bis-(5,5'-dimethyl-2,2'-bipyridyl
      kappa(2)N,N')cobalt(III) bromide trihydrate.
AB  - In the title complex, [Co(CO(3))(C(12)H(12)N(2))(2)]Br.3H(2)O, the Co(III) cation
      has a distorted octa-hedral coordination environment. It is chelated by four N
      atoms of two different 5,5'-dimethyl-2,2'-bipyridyl (dmbpy) ligands in axial and
      equatorial positions, and by two O atoms of a carbonate anion completing the
      equatorial positions. Although the water mol-ecules are disordered and their H
      atoms were not located, there are typical O?O distances between 2.8 and 3.0 A,
      indicating O-H?O hydrogen bonding. The crystal packing is consolidated by C-H?O
      and C-H?Br hydrogen bonds, as well as pi-pi stacking inter-actions between
      adjacent pyridine rings of the dmbpy ligands, with centroid-centroid distances of
      3.694 (3) and 3.7053 (3) A.

PMID- 22589774
TI  - Poly[(MU(2)-2-amino-pyrimidine-kappa(2)N(1):N(3))di-MU(2)-chlorido-mercury(II)].
AB  - The title compound, [HgCl(2)(C(4)H(5)N(3))](n), features a two-dimensional
      network parallel to (001) that is based on an Hg(II) atom octahedrally
      coordinated by four MU(2)-Cl atoms and two MU(2)-2-amino-pyrimidine (apym)
      ligands in trans positions, yielding a distorted HgCl(4)N(2) octa-hedron. The
      coordination network can be described as an uninodal 4-connected net with the sql
      topology. The Hg(II) ion lies on a site of -1 symmetry and the apym ligand lies
      on sites of m symmetry with the mirror plane perpendicular to the pyrimidine
      plane and passing through the NH(2) group N atom. This polymeric structure is
      stabilized by N-H?Cl hydrogen bonds and columnar pi-pi stacking of pyrimidine
      rings, with a centroid-centroid distance of 3.832 (2) A.

PMID- 22589775
TI  - Dichloridobis[(ferrocenyl-methyl-idene)(furan-2-ylmeth-yl)amine
      kappaN]palladium(II).
AB  - The title compound, [Fe(2)Pd(C(5)H(5))(2)(C(11)H(10)NO)(2)Cl(2)], exhibits a
      square-planar geometry at the Pd(II) atom, which is determined by inversion
      related chlorine and ferrocenyl-imine mol-ecules across a center of symmetry. The
      ferrocenyl-imine moieties are trans to each other.

PMID- 22589776
TI  - Aqua-chlorido(3,5-dinitro-2-oxidobenzo-ato-kappa(2)O(1),O(2))(1,10-phenanthroline
      kappa(2)N,N')chromium(III).
AB  - In the title compound, [Cr(C(7)H(2)N(2)O(7))Cl(C(12)H(8)N(2))(H(2)O)], the
      Cr(III) atom displays a distorted octa-hedral coordination geometry, with the
      chelating phenantroline and 3,5-dinitro-salicylate ligands in trans positions. In
      the crystal, mol-ecules are connected via O-H?O hydrogen bonds into a two
      dimensional framework parallel to (100). In addition, there are pi-pi stacking
      inter-actions between phenanthroline ligands along the c axis, with a mean inter
      planar distance of 3.456 (4) A.

PMID- 22589777
TI  - Ammonium imidazolium dichromate.
AB  - In the crystal structure of the title compound, (C(3)H(5)N(2))(NH(4))[Cr(2)O(7)],
      the anions and cations are linked through N-H?O hydrogen bonds, resulting in a
      three-dimensional structure which contains three kinds of layers parallel to
      (001). One layer contains imidazole cations, the other two layers the ammonium
      cations and dichromate anions. The dichromate anion has an eclipsed conformation
      with a dihedral angle of 14.65 (18) degrees  between the mean planes of the O-P-O
      P-O backbone.

PMID- 22589778
TI  - Bis{S-benzyl 3-[(phen-yl)(pyridin-2-yl)methyl-idene]dithio-carbazato}zinc
      acetonitrile monosolvate.
AB  - In the title compound, [Zn(C(20)H(16)N(3)S(2))(2)].CH(3)CN, two different Schiff
      base moieties coordinate to the central Zn(II) ion as tridentate N,N',S-chelating
      ligands, creating a distorted octa-hedral environment [the smallest angle being
      73.24 (6) degrees  and the widest angle being 155.73 (7) degrees ], with the two
      S atoms in cis positions. The dihedral angle between the mean planes of the two
      coordinating ligands is 83.65 (5) degrees . The crystal packing is consolidated
      by weak C-H?N hydrogen-bonding inter-actions.

PMID- 22589779
TI  - {4,4',6,6'-Tetra-bromo-2,2'-[(2,2-dimethyl-propane-1,3-di-yl)bis-(nitrilo
      methanylyl-idene)]diphenolato}copper(II).
AB  - In the title compound, [Cu(C(19)H(16)Br(4)N(2)O(2))], the Cu(II) ion and the
      substituted C atom of the diamine fragment lie on a crystallographic twofold
      rotation axis. The geometry around the Cu(II) ion is distorted square-planar,
      which is defined by the N(2)O(2) donor atoms of the coordinated Schiff base
      ligand. The dihedral angle between the symmetry-related substituted benzene rings
      is 25.33 (14) degrees . The crystal structure is stabilized by an inter-molecular
      pi-pi inter-action [centroid-centroid distance = 3.8891 (18) A].

PMID- 22589780
TI  - (Acetyl-acetonato-kappa(2)O,O')carbon-yl[tris-(naphthalen-1-yl)phosphane
      kappaP]rhodium(I) acetone hemisolvate.
AB  - The title compound, [Rh(C(5)H(7)O(2))(C(30)H(21)P)(CO)].0.5C(3)H(6)O, has two
      different complex molecules in the asymmetric unit, with the Rh(I) atoms in
      slightly distorted square-planar coordination environments. The molecules are
      packed as two monomeric mol-ecules with one acetone solvent mol-ecule sitting at
      the centre.

PMID- 22589781
TI  - Bis(4-dimethyl-amino-1-ethyl-pyridinium) bis-(1,2-dicyano-ethene-1,2-dithiol-ato
      kappa(2)S,S')nickelate(II).
AB  - The asymmetric unit of the title complex,
      (C(9)H(15)N(2))(2)[Ni(C(4)N(2)S(2))(2)], comprises one 4-dimethyl-amino-1-ethyl
      pyri-din-ium cation and one half of a [Ni(mnt)(2)](2-) (mnt(2-) = maleo-nitrile
      dithiol-ate) anion; the complete anion is generated by the application of a
      centre of inversion. The Ni(II) ion is coordinated by four S atoms of two mnt(2-)
      ligands and exhibits a square-planar coordination geometry.

PMID- 22589782
TI  - Tris(ethyl-enediamine-kappa(2)N,N')cadmium hexa-fluoridogermanate.
AB  - In the title compound, [Cd(C(2)H(8)N(2))(3)](GeF(6)), the Cd(II) atom, lying on a
      32 symmetry site, is coordinated by six N atoms from three ethyl-enediamine (en)
      ligands in a distorted octa-hedral geometry. The Ge atom also lies on a 32
      symmetry site and is coordinated by six F atoms. The en ligand has a twofold
      rotation axis passing through the mid-point of the C-C bond. The F atom is
      disordered over two sites with equal occupancy factors. In the crystal, the
      [Cd(en)(3)](2+) cations and [GeF(6)](2-) anions are connected through N-H?F
      hydrogen bonds, forming a three-dimensional supra-molecular network.

PMID- 22589783
TI  - Bis(MU-nitrito-kappa(2)O:O)bis-[bis-(1-methyl-1H-imidazole-kappaN(3))(nitrito
      kappaO)copper(II)].
AB  - In the binuclear title compound, [Cu(2)(NO(2))(4)(C(4)H(6)N(2))(4)], centro
      symmetric-ally related complex mol-ecules are linked via weak Cu-O inter-actions,
      forming dimeric units. The Cu(II) atom displays an elongated square-pyramidal
      CuN(2)O(3) coordination geometry with a slight tetra-hedral distortion of the
      basal plane [maximum deviation = 0.249 (2) A]. The dihedral angle formed by the
      imidazole rings is 26.20 (10) degrees .

PMID- 22589784
TI  - (Acetato-kappaO)(aqua-kappaO)(2-{bis-[(3,5-dimethyl-1H-pyrazol-1-yl
      kappaN(2))methyl]amino-kappaN}ethanol-kappaO)nickel(II) perchlorate monohydrate.
AB  - In the structure of the title complex,
      [Ni(CH(3)CO(2))(C(14)H(23)N(5)O)(H(2)O)]ClO(4).H(2)O, the Ni(II) centre has a
      distorted octa-hedral environment defined by one O and three N atoms derived from
      the tetra-dentate ligand, and two O atoms, one from a water mol-ecule and the
      other from an acetate anion. The mol-ecules are connected into a three
      dimensional architecture by O-H?O hydrogen bonds. The perchlorate anion is
      disordered over two positions; the major component has a site-occupancy factor of
      0.525 (19).

PMID- 22589785
TI  - Diaqua-bis-(propane-1,3-diamine)-nickel(II) bis-(propane-1,3-diamine)-disulfato
      nickelate(II).
AB  - The ionic Ni(II) title complex,
      [Ni(C(3)H(10)N(2))(2)(H(2)O)(2)][Ni(SO(4))(2)(C(3)H(10)N(2))(2)], is built up of
      [Ni(dipr)(2)(H(2)O)(2)](2+) complex cations and [Ni(dipr)(2)(SO(4))(2)](2-)
      complex anions (dipr is propane-1,3-diamine). Both Ni(II) atoms display a
      slightly distorted octa-hedral coordination and are located on inversion centers.
      There are several types of hydrogen-bonding inter-actions, which connect complex
      cations and anions into a two-dimensional network parallel to (010). Hydrogen
      bonds formed by the axially coordinated water mol-ecule of the complex cation and
      one of the O atoms of the sulfate groups of the complex anion (first type) link
      them into chains along the c axis. These chains are linked to each other through
      hydrogen bonds formed by an O atom (second type) of the SO(4) groups and NH(2)
      groups of the ligand of the complex cations from neighboring chains, forming a
      two-dimensional hydrogen-bonded net perpendicular to the b axis. The third type
      of O atoms of the sulfate groups of the complex anion are also linked into chains
      by a combination of both previously described types of H-atom connections.

PMID- 22589786
TI  - catena-Poly[[[triaqua-cobalt(II)]-MU-10-methyl-phenothia-zine-3,7-dicarboxyl-ato]
      monohydrate].
AB  - The polymeric title compound, {[Co(C(15)H(9)NO(4)S)(H(2)O)(3)].H(2)O}(n),
      consists of chains along [001] made up from Co(2+) ions bridged by 10-methyl
      phenothia-zine-3,7-dicarboxyl-ate anions. The Co(2+) ion, coordinated by three O
      atoms from two different carboxyl-ate groups and three water mol-ecules, displays
      a distorted octa-hedral environment. In the crystal, pi-pi inter-chain inter
      actions, with centroid-centroid distances of 3.656 (2) and 3.669 (2) A between
      the benzene rings of the ligands, assemble the chains into sheets parallel to
      (100). O-H?O hydrogen-bonding inter-actions between the coordinating water mol
      ecules and carboxyl-ate O atoms link the sheets into a three-dimensional network.

PMID- 22589787
TI  - trans-Dichloridobis[dicyclo-hex-yl(phen-yl)phosphane-kappaP]palladium(II).
AB  - The title compound, [PdCl(2){P(C(6)H(11))(2)(C(6)H(5))}(2)], forms a monomeric
      complex with a trans-square-planar geometry. The Pd-P bond lengths are 2.3343 (5)
      A, as the Pd atom lies on an inversion centre, while the Pd-Cl bond lengths are
      2.3017 (4) A. The observed structure was found to be closely related to
      [PdCl(2){P(C(6)H(11))(3)}(2)] [Grushin et al. (1994 ?). Inorg. Chem.33, 4804
      4806], [PdBr(2){P(C(6)H(11))(3)}(2)] [Clarke et al. (2003 ?). Dalton Trans. pp.
      4393-4394] and [PdCl(2)P(C(6)H(11))(2)(C(7)H(7))}(2)] [Vuoti et al. (2008 ?).
      Eur. J. Inorg. Chem. pp. 397-407] (C(6)H(11) is cyclo-hexyl and C(7)H(7) is o-tol
      yl). One of the cyclo-hexyl rings is disordered with the phenyl ring in a 0.587
      (9):413 (9) ratio. Five long-range C-H?Cl inter-actions were observed within the
      structure.

PMID- 22589788
TI  - catena-Poly[[tetra-kis-(1H-pyrazole-kappaN(2))copper(II)]-MU-hexa
      fluoridosilicato-kappa(2)F:F'].
AB  - In the title one-dimensional coordination polymer,
      [Cu(SiF(6))(C(3)H(4)N(2))(4)](n), the Cu(II) atom is coordinated by two
      hexafluoridosilicate F atoms and four pyrazole N atoms in a distorted trans
      CuF(2)N(4) octa-hedral environment. The dihedral angle between the planes of the
      pyrazlole rings in the asymmetric unit is 74.4 (3) degrees . The hexa
      fluoridosilicate dianion acts as a bridging ligand, connecting the Cu(II) atoms
      into a [1-10] chain. The Cu and Si atoms lie on special positions with 2/m site
      symmetry. In the crystal, intra-chain N-H?F hydrogen bonds occur and weak C-H?F
      inter-actions link the chains.

PMID- 22589789
TI  - catena-Poly[[(dichloridozinc)-MU-4,4'-bis-(1H-imidazol-1-yl)biphenyl
      kappa(2)N(3):N(3')] 0.25-hydrate].
AB  - In the title one-dimensional coordination polymer,
      {[ZnCl(2)(C(18)H(14)N(4))].0.25H(2)O}(n), the Zn(II) atom is coordinated by two
      chloride ions and two 4,4'-bis-(1H-imidazol-1-yl)biphenyl ligands, generating a
      distorted tetra-hedral ZnCl(2)N(2) geometry. The dihedral angle between the
      benzene rings of the ligand is 51.0 (1) degrees  and the dihedral angles between
      the benzene rings and their attached imidazole rings are 18.7 (2) and 45.9 (1)
      degrees . The bridging ligand leads to [10-1] polymeric chains in the crystal and
      the disordered water mol-ecule (occupancy 0.25) forms O-H?Cl hydrogen bonds.

PMID- 22589790
TI  - 3,5-Dimethyl-1-(4-nitro-benz-yl)pyridinium bis-(benzene-1,2-dithiol-ato
      kappa(2)S,S')nickelate(III).
AB  - The asymmetric unit of the title compound,
      (C(14)H(15)N(2)O(2))[Ni(C(6)H(4)S(2))(2)], contains one cation and two halves of
      two centrosymmetric crystallographically independent anions. In the anions, the
      Ni(III) atoms are coordinated by four S atoms in a distorted square-planar
      geometry. In the cation, the dihedral angle between the pyridine and benzene
      rings is 88.66 (17) degrees . In the crystal, anions and cations inter-act
      through C-H?S and C-H?O hydrogen bonds.

PMID- 22589791
TI  - trans-Tetra-kis[N-(adamantan-1-yl)pyridine-4-carboxamide]-dichlorido
      manganese(II)-N-(adamantan-1-yl)pyridine-4-carboxamide (1/2).
AB  - The asymmetric unit of the title compound,
      [MnCl(2)(C(16)H(20)N(2)O)(4)].2C(16)H(20)N(2)O, is composed of two coordinating N
      (adamantan-1-yl)pyridine-4-carboxamide mol-ecules, one Cl(-) anion, an Mn(II)
      ion, lying on an inversion centre, and one free N-(adamantan-1-yl)pyridine-4
      carboxamide mol-ecule. The distorted octa-hedral Mn environment comprises two
      terminal Cl atoms and four monodentate N atoms from four organic ligands. All the
      carbamoyl N atoms are involved in inter-molecular N-H?O hydrogen-bonding inter
      actions which link the mol-ecules into a chain along the a axis.

PMID- 22589792
TI  - Tetra-kis(MU-2-iodo-benzoato-kappa(2)O:O')bis-[aqua-copper(II)].
AB  - In the centrosymmetric binuclear title complex,
      [Cu(2)(C(7)H(4)IO(2))(4)(H(2)O)(2)], the two Cu(II) ions [Cu?Cu = 2.6009 (5) A]
      are bridged by four 2-iodo-benzoate (IB) ligands. The four nearest O atoms around
      each Cu(II) ion form a distorted square-planar arrangement, the distorted square
      pyramidal coordination being completed by the O atom of the water mol-ecule at a
      distance of 2.1525 (16) A. The dihedral angle between the benzene ring and the
      carboxyl-ate group is 25.67 (13) degrees  in one of the independent IB ligands
      and 6.44 (11) degrees  in the other. The benzene rings of the two independent IB
      ligands are oriented at a dihedral angle of 86.61 (7) degrees . In the crystal, O
      H?O inter-actions link the mol-ecules into a two-dimensional network. pi-pi
      contacts between the benzene rings [centroid-centroid distances = 3.810 (2) and
      3.838 (2) A] may further stabilize the structure.

PMID- 22589793
TI  - (2,2'-Bipyridine-6,6'-dicarboxyl-ato-kappa(3)N,N',O(6))(6'-carb-oxy-2,2'
      bipyridine-6-carboxyl-ato-kappa(3)N,N',O(6))cobalt(III).
AB  - The Co(III) atom in the title compound,
      [Co(C(12)H(6)N(2)O(4))(C(12)H(7)N(2)O(4))], is six-coordinated in a distorted
      octa-hedral geometry by four N atoms and two O atoms of the chelating 2,2'
      bipyridine-6,6'-dicarboxyl-ate and 6'-carb-oxy-2,2'-bipyridine-6-carboxyl-ate
      ligands. Intermolecular O-H?O hydrogen bonds and face-to-face pi-stacking inter
      actions [centroid-centroid distance = 3.6352 (16) A] between inversion-related
      pyridine rings link adjacent mononuclear units into a two-dimensional supra
      molecular structure, and several inter-molecular C-H?O inter-actions are also
      observed.

PMID- 22589794
TI  - cis-Tetra-aqua-bis-{5-[4-(1H-imidazol-1-yl-kappaN(3))phen-yl]tetra
      zolido}manganese(II) dihydrate.
AB  - In the title compound, [Mn(C(10)H(7)N(6))(2)(H(2)O)(4)].2H(2)O, the complex unit
      comprises an Mn(2+) ion, coordinated by two imidazole N atoms from cis-related
      monodentate 5-[4-(imidazol-1-yl)phen-yl]tetra-zolide ligands and four water mol
      ecules, together with two water mol-ecules of solvation. The Mn(2+) ion lies on a
      twofold rotation axis and has a slightly distorted octa-hedral geometry. The mol
      ecules are connected by O-H?N and O-H?O hydrogen bonds involving both coordinated
      and solvent water mol-ecules, generating a three-dimensional structure. Two C
      atoms of the imidazole ring of the ligand are each disordered over two sites with
      occupancy factors of 0.75 and 0.25.

PMID- 22589795
TI  - Poly[(MU(4)-benzene-1,3,5-tricarboxyl-ato)bis-(N,N-dimethyl-acetamide)
      terbium(III)].
AB  - The title compound, [Tb(C(9)H(3)O(6))(C(4)H(9)NO)(2)], shows a rare-earth three
      dimensional metal-organic framework structure. In this complex of an eight
      coordinated Tb(3+) ion, the asymmetric unit contains one benzene-1,3,5-tricarb
      oxy-lic ligand and two coordinated dimethyl-acetamide mol-ecules. Each Tb(3+) ion
      is coordinated by six O atoms from four carboxyl-ate groups of the benzene-1,3,5
      tricarb-oxy-lic ligands and two O atoms from two terminal dimethyl-acetamide mol
      ecules.

PMID- 22589796
TI  - Bis(1H-benzimidazole-kappaN(3))bis-[2-(naphthalen-1-yl)acetato
      kappa(2)O,O']nickel(II) monohydrate.
AB  - In the title compound, [Ni(C(12)H(9)O(2))(2)(C(7)H(6)N(2))(2)].H(2)O, The Ni(II)
      cation is located on a twofold rotation axis and is six-coordinated in a
      distorted NiN(2)O(4) octa-hedral geometry. The asymmetric unit consists of a
      nickel(II) ion, one 2-(naphthalen-1-yl)acetate anion, a neutral benzotriazole
      ligand and one half of a lattice water mol-ecule. The crystal packing is
      stabilized by O-H?O and N-H?O hydrogen bonds. The title compound is isotypic with
      its Cd(II) analogue.

PMID- 22589797
TI  - cis-Bis[(4-nitro-phen-yl)cyanamido-kappaN(1)]bis-(1,10-phenanthroline
      kappa(2)N,N')nickel(II) methanol monosolvate.
AB  - In the title compound, [Ni(C(7)H(4)N(3)O(2))(2)(C(12)H(8)N(2))(2)].CH(3)OH, the
      Ni(II) atom is six-coordinated in a distorted N(6) octa-hedral geometry and is
      chelated by two phenanthroline ligands and two phenyl-cyanamide groups which
      occupy cis positions. The (4-nitro-phen-yl)cyanamide anions act as monodentate
      ligands. There is one classical inter-molecular O-H?N hydrogen bond and several C
      H?O hydrogen bonds are also observed.

PMID- 22589798
TI  - [2-(Dimethyl-amino)-ethanol-kappa(2)N,O][2-(dimethyl-amino)-ethano-lato
      kappa(2)N,O]iodidocopper(II).
AB  - The title compound, [Cu(C(4)H(10)NO)I(C(4)H(11)NO)], was obtained unintentionally
      as the product of an attempted synthesis of a Cu/Zn mixed-metal complex using
      zerovalent copper, zinc(II) oxide and ammonium iodide in pure 2-(dimethyl-amino)
      ethanol, in air. The mol-ecular complex has no crystallographically imposed
      symmetry. The coordination geometry around the metal atom is distorted square
      pyramidal. The equatorial coordination around copper involves donor atoms of the
      bidentate chelating 2-(dimethyl-amino)-ethanol ligand and the 2-(dimethyl-amino)
      ethano-late group, which are mutually trans to each other, with four
      approximately equal short Cu-O/N bond distances. The axial Cu-I bond is substanti
      ally elongated. Inter-molecular hydrogen-bonding inter-actions involving the -OH
      group of the neutral 2-(dimethyl-amino)-ethanol ligand to the O atom of the
      monodeprotonated 2-(dimethyl-amino)-ethano-late group of the mol-ecule related by
      the n-glide plane, as indicated by the O?O distance of 2.482 (12) A, form chains
      of mol-ecules propagating along [101].

PMID- 22589799
TI  - Triethyl-ammonium (indane-1,2,3-trione 1,2-dioximato-kappa(2)N(1),O(2))(indane
      1,2,3-trione 2-oximato 1-oxime-kappa(2)N(1),O(2))nickel(II).
AB  - In the title compound, (C(6)H(16)N)[Ni(C(9)H(4)N(2)O(3))(C(9)H(5)N(2)O(3))], the
      Ni(II)ion is four-coordinated by two N atoms and two O atoms from two indane
      1,2,3-trione-1,2-dioxime ligands. The two organic ligands are linked by an intra
      molecular O-H?O hydrogen bond. In the crystal, mol-ecules are linked by N-H?O
      hydrogen-bonds.

PMID- 22589800
TI  - Poly[diaquadi-MU-hydroxido-kappa(4)O:O-dinitrato-kappa(4)O:O'-bis-[3-(pyridin-4
      yl-kappaN)-5-(pyridin-3-yl)-1,2,4-oxadiazole]dicopper(II)].
AB  - The title compound, [Cu(2)(NO(3))(2)(OH)(2)(C(12)H(8)N(4)O)(2)(H(2)O)(2)](n),
      consists of a neutral polymeric Cu(II) complex in which each Cu(II) atom has a
      distorted octa-hedral geometry defined by a pyridyl N atom from a 3-(pyridin-3
      yl)-5-(pyridin-4-yl)-1,2,4-oxadiazole ligand and five O atoms from a water mol
      ecule, two nitrates and two hydroxides. Two Cu(II) ions are bridged by two
      hydroxide anions resulting in a Cu(2)O(2) loop, located across an inversion
      center and connected by the nitrate anions into a broad two-dimensional polymeric
      structure parallel to (100). In the crystal, there are O-H?O hydrogen bonds
      between the coodinated water mol-ecule and the nitrate and hydroxide, and between
      the hydroxide and the nitrate. Inter-molecular pi-pi inter-actions are present
      between pyridine rings in adjacent two-dimensional structures, with a centroid
      centroid distance of 3.582 (2) A.

PMID- 22589801
TI  - Bromido(2,4,6-trimethyl-phen-yl)mercury(II).
AB  - Mol-ecules of the title compound, [HgBr(C(9)H(11))], are located on a
      crystallographic twofold rotation axis. Due to the mol-ecular symmetry, the
      Hg(II) atom is linearly coordinated by the ipso-C of the mesityl group and the Br
      atom. In the crystal, mol-ecules lie in planes parallel to (001).

PMID- 22589802
TI  - Bis(propane-1,3-diamine)-disaccharinatonickel(II).
AB  - In the title complex, [Ni(C(7)H(4)NO(3)S)(2)(C(3)H(10)N(2))(2)] or
      [Ni(sac)(2)(pen)(2)] (sac = saccharinate or 1,1,3-trioxo-2,3-dihydro-1lambda(6,2)
      benzothia-zol-2-ide and pen = propane-1,3-diamine), the Ni(II) ion sits on an
      inversion center, being coordinated by two N atoms of the sac ligands, which
      occupy trans positions, and four N atoms of the bidentate pen ligands to define a
      distorted octa-hedral geometry. The pen ligands chelate the metal ion, forming a
      six-membered ring which adopts a half-chair conformation, while the sac ligands
      adopt the most common coordination mode. The crystal packing is stabilized by N
      H?O hydrogen bonds, which form a one-dimensional network along [010]. It is also
      supported by an N-H?S hydrogen bond between the amine group of the pen ligand and
      the sulfonyl group of the sac ligand.

PMID- 22589803
TI  - Bis(azido-kappaN)bis-[6-(pyridin-2-yl)-1,3,5-triazine-2,4-diamine
      kappa(2)N(1),N(6)]manganese(II).
AB  - In the title complex, [Mn(N(3))(2)(C(8)H(8)N(6))(2)], the complete molecule is
      generated by the application of twofold symmetry, and is in a distorted octa
      hedral environment, coordinated by four N atoms of two bidentate 6-(pyridin-2-yl)
      1,3,5-triazine-2,4-diamine ligands and two N atoms from two azide anions. The two
      chelated 6-(pyridin-2-yl)-1,3,5-triazine-2,4-diamine ligands form a dihedral
      angle 74.75 (5) degrees . The mononuclear mol-ecules are alternatively linked
      into layers parallel to the ac plane via N-H?N hydrogen bonds. Adjacent layers
      are connected into a three-dimensional supra-molecular framework by futher N-H?N
      hydrogen-bonding inter-actions.

PMID- 22589804
TI  - [Disulfanediylbis(ferrocenyl-thio-phosphinato)-kappa(2)O,O]titanocene tetra-hydro
      furan tris-olvate.
AB  - The title compound, [Fe(2)Ti(C(5)H(5))(4))(C(10)H(8)O(2)P(2)S(4))].3C(4)H(8)O,
      contains a central seven-membered TiO(2)P(2)S(2) ring with a very similar
      geometry compared to the derivative showing anisyl instead of ferrocenyl
      substituents, the Ti-O distance being marginally longer for the anisyl
      derivative. Two tetra-hydro-furan solvent mol-ecules are each disordered on a
      twofold axis.

PMID- 22589805
TI  - catena-Poly[[[2-({6-[(pyrimidin-2-ylsulfanyl-kappaS)meth-yl]pyridin-2-yl
      kappaN}methyl-sulfan-yl)pyrimidine]-copper(I)]-MU-thio-cyanato-kappa(2)N:S].
AB  - The N-heterocyclic ligand in the title compound,
      [Cu(NCS)(C(15)H(13)N(5)S(2))](n), coordinates to the Cu(I) atom through its
      pyridine N-donor site, and adjacent metal atoms are bridged by the thio-cyanate
      ion, forming a helical chain along the b axis. The geometry of the metal atom is
      tetra-hedral owing to a somewhat long intra-molecular Cu-S inter-action of 2.5621
      (9) A.

PMID- 22589807
TI  - Dichloridobis(2-phenyl-pyridine-kappaN)zinc(II).
AB  - In the title compound, [ZnCl(2)(C(11)H(9)N)(2)], the Zn(2+) cation lies on a
      twofold axis and is coordinated by two Cl(-) anions and the N atoms of two 2
      phenyl-pyridine ligands, forming a ZnN(2)Cl(2) polyhedron with a slightly
      distorted tetra-hedral coordination geometry. The dihedral angle between the
      phenyl ring and the metal-bound pyridine ring is 50.3 (4) degrees  for each 2
      phenyl-pyridine ligand. This arranges the phenyl ring from one ligand in the
      complex above the pyridine ring of the other resulting in an intra-molecular pi
      pi inter-action, with a centroid-centroid distance of 3.6796 (17) A. Weak C-H?Cl
      hydrogen bonds stabilize the crystal packing, linking mol-ecules into chains
      along the c axis.

PMID- 22589806
TI  - Poly[di-MU(3)-chlorido-di-MU(2)-chlorido-{MU(4)-N,N,N',N'-tetra-kis-[(diphenyl
      phosphan-yl)meth-yl]benzene-1,4-diamine-kappa(4)P:P':P'':P'''}tetra-copper(II)].
AB  - In the title complex, [Cu(4)Cl(4)(C(58)H(52)N(2)P(4))](n), four Cu(II) atoms are
      held together via two doubly bridging and two triply bridging chlorides, forming
      a stair-like Cu(4)Cl(4) core having crystallographically imposed inversion
      symmetry, while the benzene-1,4-diamine ligand (with a crystallographic inversion
      center at the centroid) acts in a tetra-dentate coordination mode, bridging two
      adjacent Cu(4)Cl(4) cores, resulting in a chain along the a-axis direction. One
      Cu atom has a distorted tetra-hedral geometry, coordinated by one P atom, one
      MU(2)-Cl and two MU(3)-Cl atoms, while the second Cu atom adopts a trigonal
      geometry, coordinated by one P atom, one MU(2)-Cl and one MU(3)-Cl atoms.

PMID- 22589808
TI  - cis-Tetra-aqua-bis-{5-[4-(1H-imidazol-1-yl-kappaN(3))phen-yl]tetra
      zolido}manganese(II) dihydrate.
AB  - In the title compound, [Mn(C(10)H(7)N(6))(2)(H(2)O)(4)].2H(2)O, the Mn(2+) lies
      on a twofold rotation axis and is six-coordinated by two N atoms from the cis
      related monodentate 5-[4-(imidazol-1-yl)phen-yl]tetra-zolide ligands and four O
      atoms from the coordinated water mol-ecules. The complex mol-ecules are connected
      via water O-H?O and O-H?N hydrogen bonds and weak pi-pi stacking inter-actions
      between the benzene rings [minimum ring centroid separation = 3.750 (6) A] into a
      three-dimensional polymeric structure. The imidazolyl group of the ligand is
      partially disordered over two sets of sites with refined occupancies of 0.531
      (7):0.469 (7).

PMID- 22589809
TI  - Chlorido{4-cyclo-hexyl-1-[1-(pyridin-2-yl-kappaN)ethyl-idene]thio-semicarbazidato
      kappa(2)N(1),S}diphenyl-tin(IV).
AB  - The distorted octa-hedral geometry about the Sn(IV) atom in the title compound,
      [Sn(C(6)H(5))(2)(C(14)H(19)N(4)S)Cl], is defined by the N,N,S-tridentate Schiff
      base ligand, two mutually trans ipso-C atoms of the Sn-bound phenyl groups, and
      the Cl atom which is trans to the azo N atom. The two five-membered chelate rings
      and pyridyl ring are almost coplanar with the dihedral angle between the outer
      five-membered chelate and pyridine rings being 5.39 (8) degrees . Centrosymmetric
      dimers feature in the crystal packing mediated by N-H?S hydrogen bonds, leading
      to eight-membered {?HNCS}(2) synthons. The dimeric aggregates are connected into
      a three-dimensional architecture by C-H?Cl and C-H?pi inter-actions, as well as
      pi-pi inter-actions occurring between centrosymmetrically related pyridine rings
      [centroid-centroid distance = 3.6322 (13) A].

PMID- 22589810
TI  - Tetra-MU-benzoato-bis-[(3,5-dimethyl-pyridine)-copper(II)].
AB  - In the centrosymmetric binuclear title compound,
      [Cu(2)(C(7)H(5)O(2))(4)(C(7)H(9)N)(2)], the Cu(II) atom is coordinated by four O
      atoms from benzoate anions and one N atom from a dimethyl-pyridine ligand. A
      paddle-wheel-like dimer is formed by two Cu(II) ions and four benzoate anions
      with two 3,5-dimethyl-pyridine ligands at the axial position of the Cu(II) ions.
      The dihedral angle between the two unique benzene rings is 84.26 (16) degrees .
      The dihedral angles between the pyridine ring and the benzene rings are 61.67
      (15) and 34.27 (14) degrees . There is pi-pi stacking of inversion-related
      pyridine rings, with a centroid-centroid distance of 3.833 (2) A.

PMID- 22589811
TI  - Tris(4-methyl-anilinium) penta-chlorido-anti-monate(III) chloride monohydrate.
AB  - The title compound, (C(7)H(10)N)(3)[SbCl(5)]Cl.H(2)O, consists of 4-methyl
      anilinium cations, Cl(-) and [SbCl(5)](2-) anions and water mol-ecules. The five
      Cl atoms bound to Sb [Sb-Cl = 2.4043 (9)-2.6262 (11) A] form a square-pyramidal
      coordination environment. In addition, two [SbCl(5)](2-) anions related by an
      inversion center are joined by Sb?Cl inter-actions [Sb?Cl = 3.7273 (14) A] into
      an [Sb(2)Cl(10)](4-) dimer with two bridging Cl atoms. The anions, water mol
      ecules and ammonium groups of the cations are linked by N-H?Cl, N-H?O and O-H?Cl
      hydrogen bonds, forming layers parallel to the ac plane. The benzene rings of the
      4-methyl-anilinium cations are packed between these layers.

PMID- 22589812
TI  - Dichloridotris(2-methyl-1H-imidazole-kappaN(3))cadmium.
AB  - In the title compound, [CdCl(2)(C(4)H(6)N(2))(3)], the Cd(II) atom displays a
      penta-coordinate CdN(3)Cl(2) coordination geometry, being coordinated by an N
      atom of three 2-methyl-imidazole ligands and two Cl atoms. In the crystal, the
      mononuclear complexes are linked by N-H?Cl hydrogen bonds into a two-dimensional
      network in the ab plane.

PMID- 22589813
TI  - cis-(Di-2-pyridyl-amine-kappa(2)N(2),N(2'))bis-(thio-cyanato-kappaS)platinum(II).
AB  - In the title complex, [Pt(NCS)(2)(C(10)H(9)N(3))], the Pt(II) ion is four
      coordinated in a distorted square-planar environment by the two pyridine N atoms
      of the chelating di-2-pyridyl-amine (dpa) ligand and two mutually cis S atoms
      from two linear thio-cyanate anions. The dpa ligand is not planar, the dihedral
      angle between the pyridine rings being 30.8 (4) degrees . In the crystal, the
      complex mol-ecules are stacked in columns along the a axis and are connected by
      inter-molecular N-H?N hydrogen bonds, forming supra-molecular chains along the b
      axis.

PMID- 22589814
TI  - Bis(3-acetyl-pyridine-kappaN)bis-(methanol-kappaO)bis-(thio-cyanato
      kappaN)nickel(II).
AB  - In the crystal structure of the title compound,
      [Ni(NCS)(2)(C(7)H(7)NO)(2)(CH(3)OH)(2)], the Ni(2+) cations are coordinated by
      two thio-cyanate anions, two 3-acetyl-pyridine ligands and two methanol mol
      ecules within slightly distorted NiN(4)O(2) octa-hedra. The asymmetric unit
      consists of one Ni(2+) cation, which is located on a center of inversion, as well
      as one thio-cyanate anion, one 3-acetyl-pyridine ligand and one methanol mol
      ecule in general positions. The discrete complexes are linked by two pairs of O
      H?O hydrogen bonds between the hy-droxy H atom and the acetyl O atom into chains
      along the b axis.

PMID- 22589815
TI  - (2,9-Dimethyl-1,10-phenanthroline-kappa(2)N,N')bis-(2-meth-oxy-benzoato
      kappa(2)O(1),O(1'))cadmium.
AB  - In the title compound, [Cd(C(8)H(7)O(3))(2)(C(14)H(12)N(2))], the Cd(II) ion is
      coordinated by two N atoms from a 2,9-dimethyl-1,10-phenanthroline (dmphen)
      ligand and four O atoms from two 2-meth-oxy-benzoate anions in a distorted octa
      hedral environment. Two O atoms of one bidentate 2-meth-oxy-benzoate ligand are
      each disordered over two positions, with site-occupancy factors of 0.579 (4) and
      0.421 (4). In the crystal, mol-ecules are linked by C-H?O hydrogen bonds, forming
      a two-dimensional network lieing parallel to the bc plane. The crystal packing is
      further stablized by pi-pi stacking inter-actions between the dmphen rings of
      neighboring mol-ecules, with distances between their parallel dmphen ring planes
      of 3.517 (3) and 3.610 (3) A.

PMID- 22589816
TI  - Poly[tetra-aqua-bis-(MU(3)-oxalato-kappa(5)O(1),O(2):O(1'):O(1'),O(2'))(MU(2)
      oxalato-kappa(4)O(1),O(2):O(1'),O(2'))dipraseodymium(III)].
AB  - In the title complex, [Pr(2)(C(2)O(4))(3)(H(2)O)(4)](n), the two independent
      Pr(III) ions are both nine-coordinated in a distorted monocapped square-anti
      prismatic geometry by seven O atoms from four oxalate ligands and two water mol
      ecules. The Pr(III) ions are bridged by the oxalate ligands, forming a layer
      parallel to (001). O-H?O hydrogen bonds connect the layers.

PMID- 22589817
TI  - catena-Poly[[triaquacopper(II)]-MU(2)-furan-2,5-dicarboxyl-ato
      kappa(4)O(1),O(2):O(2),O(2')].
AB  - In the title compound, [Cu(C(6)H(2)O(5))(H(2)O)(3)](n), an infinite chain is
      formed along [001] by linking of the Cu(OH(2))(3)O(4) cluster with one carboxyl
      ate group of the furan-2,5-dicarboxyl-ate ligand. Adjacent chains are linked by
      O(water)-H?O hydrogen-bonding inter-actions. The Cu(OH(2))(3)O(4) cluster
      displays a penta-gonal bipyrimadal geometry with two weak coordinations [Cu
      O(furan) = 2.790 (2) A) and Cu-O(carboxyl-ate) = 2.684 (2) A] and two water mol
      ecules located in axial positions.

PMID- 22589818
TI  - trans-Diaqua-bis-(l-phenyl-alaninato-kappa(2)N,O)nickel(II).
AB  - In the title compound, [Ni(C(9)H(10)NO(2))(2)(H(2)O)(2)], the coordination
      geometry around the Ni(II) ion can be described as distorted octa-hedral, with
      two N atoms and two O atoms from phenyl-alaninate ligands in the basal plane and
      two aqua O atoms at the axial sites. The crystal packing is stabilized by inter
      molecular O-H?O and N-H?O hydrogen bonds.

PMID- 22589819
TI  - Tetra-kis(azido-kappaN)(di-2-pyridyl-amine-kappa(2)N(2),N(2'))platinum(IV).
AB  - In the title complex, [Pt(N(3))(4)(C(10)H(9)N(3))], the Pt(IV) ion is six
      coordinated in a slightly distorted octa-hedral environment by the two pyridine N
      atoms of the chelating di-2-pyridyl-amine (dpa) ligand and four N atoms from four
      azide anions. The dpa ligand is not planar, the dihedral angle between the
      pyridine rings being 20.0 (3) degrees . The azide ligands are slightly bent [N-N
      N = 173.5 (8)-175.1 (8) degrees ]. In the crystal, the complex mol-ecules are
      connected by N-H?N hydrogen bonds, forming a chain along the b axis. An inter
      molecular pi-pi inter-action between the chains is also present, the ring
      centroid-centroid distance being 3.713 (4) A.

PMID- 22589820
TI  - Bis(cyclo-hexyl-ammonium) tetra-bromido-cuprate(II).
AB  - The structure of the title salt, (C(6)H(14)N)(2)[CuBr(4)], is built up from cyclo
      hexyl-ammonium cations and tetra-bromidocuprate anions, the latter being located
      on an inversion center. In the crystal, anions and cations are inter-connected by
      N-H?Br hydrogen bonds, forming ribbons parallel to [0-11].

PMID- 22589821
TI  - Poly[bis(MU-purin-9-ido-kappa(2)N(7):N(9))zinc].
AB  - In the title compound, [Zn(C(5)H(3)N(4))(2)], the Zn(II) cation is in a nearly
      regular tetra-hedral coordination by purinate ligands. Each purinate ligand
      chelates two Zn(II) cations through two imidazole N atoms of the purinate anion
      ligand, leading to the formation of a three-dimensional network.

PMID- 22589822
TI  - (8-Amino-quinoline-kappa(2)N,N')bis-(1,1,1,5,5,5-hexa-fluoro-pentane-2,4-dionato
      kappa(2)O,O')cobalt(II).
AB  - In the title compound, [Co(C(5)HF(6)O(2))(2)(C(9)H(8)N(2))], the Co(II) centre
      exhibits a pseudooctahedral coordination geometry, comprising two N-atom donors
      from the bidentate amino-quinoline ligand and four O-atom donor atoms from two
      bidentate chelating 1,1,1,5,5,5-hexafluoropentane-2,4-dionate ligands. In the
      crystal, molecules are linked via pairs of N-H?O hydrogen bonds, forming
      inversion dimers. These dimers are further connected through pi-pi interactions
      between neighbouring quinoline rings [centroid-centroid distance = 3.472 (2) A],
      and stack along the c axis.

PMID- 22589823
TI  - Poly[[diaqua-bis-[MU(4)-5-nitro-isophthalato-kappa(4)O(1):O(1):O(3):O(3')]bis
      [MU(3)-pyridine-4-carboxyl-ato-kappa(3)O:O':N]tricobalt(II)] tetra-hydrate].
AB  - The title compound,
      {[Co(3)(C(6)H(4)NO(2))(2)(C(8)H(3)NO(6))(2)(H(2)O)(2)].4H(2)O}(n), exhibits a two
      dimensional layer-like structure in which the Co(II) ions exhibit two kinds of
      coordination geometries. One nearly octa-hedral Co(II) ion with crystallographic
      inversion symmetry is coordinated to six carboxyl-ate O atoms from four bridging
      5-nitro-isophthalate (NIPH) ligands and two isonicotinate (IN) anions, while the
      other type of Co(II) ion binds with one N atom and one carboxyl-ate O atom from
      two IN anions, two carboxyl-ate O atoms from two different NIPH anions and one
      ligated water mol-ecule, displaying a distorted square-pyramidal coordination
      geometry. Three adjacent Co(II) ions are bridged by six carboxyl-ate groups from
      four NIPH ligands and two IN anions to form a linear trinuclear secondary
      building unit (SBU). Every trinuclear SBU is linked to its nearest neighbours in
      the ab plane, resulting in a two-dimensional layer-like structure perpendicular
      to the c axis. Along the a-axis direction neighbouring mol-ecules are connected
      through carboxyl-ate and pyridyl units of the IN anions, along the b axis through
      carboxyl-ate groups of the NIPH ligands. The H atoms of one free water mol-ecule
      are disordered in the crystal in a 1:1 ratio. Typical O-H?O hydrogen bonds are
      observed in the lattice, which include the following contacts: (a) between
      coordinated water mol-ecules and carboxyl-ate O atoms of the NIPH anions, (b)
      between lattice water mol-ecules and carboxyl-ate O atoms of the NIPH anions, and
      (c) between coordinated and lattice water mol-ecules. These inter-molecular
      hydrogen bonds connect the two-dimensional layers to form a three-dimensional
      supra-molecular structure.

PMID- 22589824
TI  - Dibromido(di-2-pyridyl-amine-kappa(2)N(2),N(2'))platinum(II).
AB  - The Pt(II) ion in the title complex, [PtBr(2)(C(10)H(9)N(3))], is four
      coordinated in an essentially square-planar environment by two N atoms from a
      chelating di-2-pyridyl-amine (dpa) ligand and two Br(-) anions. The dpa ligand is
      not planar, with the dihedral angle between the pyridine rings being 40.8 (2)
      degrees . The complex mol-ecules are stacked in columns along [001] through pi-pi
      inter-actions between the pyridine rings [centroid-centroid distances = 3.437 (3)
      and 3.520 (3) A]. Inter-molecular N-H?Br hydrogen bonds connect the mol-ecules
      into chains running along [010]. Intra-molecular C-H?Br interactions are also
      observed.

PMID- 22589825
TI  - (Acridine-kappaN)(pyridine-2,6-dicarboxyl-ato-kappa(3)O(2),N,O(6))palladium(II).
AB  - In the title complex, [Pd(C(7)H(3)NO(4))(C(13)H(9)N)], the Pd(II) ion is four
      coordinated in a distorted square-planar environment by one N and two O atoms
      from the tridentate pyridine-2,6-dicarboxyl-ate (dipic) anionic ligand and one N
      atom of the acridine (acr) ligand. The dipic and acr ligands are nearly planar
      [maximum deviation = 0.069 (3) A in dipic and 0.091 (4) A in acr] and the
      dihedral angle between their mean planes is 58.67 (7) degrees . The Pd-O bond
      lengths are nearly equal, but the Pd-N bond lengths are slightly different. There
      is a short C-H?O inter-action in the mol-ecule involving the two ligands. In the
      crystal, complex mol-ecules are linked through C-H?O inter-actions, forming a
      three-dimensional network. There are also a number of inter-molecular pi-pi inter
      actions present, the shortest ring centroid-centroid distance being 3.622 (3) A.

PMID- 22589826
TI  - Aqua-chlorido{6,6'-dimeth-oxy-2,2'-[ethane-1,2-diylbis(nitrilo-methanylyl
      idene)]diphenolato-kappa(2)O(1),N,N',O(1')}cobalt(III) dimethyl-formamide
      monosolvate.
AB  - In the title compound, [Co(C(18)H(18)N(2)O(4))Cl(H(2)O)].C(3)H(7)NO, the Co(III)
      ion is six-coordinated by a tetra-dentate 6,6'-dimeth-oxy-2,2'-[ethane-1,2
      diylbis(nitrilo-methanylyl-idene)]diphenolate ligand, with a chloride ion and an
      aqua ligand in the apical positions. The compound crystallized as a dimethyl
      formamide (DMF) monosolvate. In the crystal, complex mol-ecules are linked via O
      H(water)?O hydrogen bonds to form a dimer-like arrangement. These dimers are
      linked via a C-H?Cl inter-action, and the DMF mol-ecule is linked to the complex
      mol-ecule by C-H?O inter-actions.

PMID- 22589827
TI  - Bis-(4-benzoyl-3-methyl-1-phenyl-4,5-di-hydro-1H-pyrazol-5-olato
      kappa(2)O,O')(methanol-kappaO)dioxidouranium(VI) methanol monosolvate.
AB  - In the title compound, [U(C(17)H(13)N(2)O(2))(2)O(2)(CH(3)OH)].CH(3)OH, the U(VI)
      ion is coordinated by seven O atoms in a distorted pentagonal-bipyramidal
      geometry with two 3-methyl-1-phenyl-4-benzoyl-4,5-dihydro-1H-pyrazol-5-olate
      groups with two O atoms in a bidentate chelating coordination mode and by three O
      atoms, one of which is from a methanol ligand. The crystal packing can be
      described by alternating layers of complex mol-ecules along the a axis. The
      structure is stabilized by O-H?N and O-H?O hydrogen bonding and van der Waals
      inter-actions.

PMID- 22589828
TI  - Tetra-kis(nitrato-kappa(2)O,O')[N,N'-1,4-phenyl-enebis(pyridine-4-carboxamide)
      kappaN(1)](4-{[4-(pyridine-4-carboxamido-kappaN(1))phen-yl]carbamo-yl}pyridin-1
      ium)neodymium(III).
AB  - In the title compound, [Nd(NO(3))(4)(C(18)H(15)N(4)O(2))(C(18)H(14)N(4)O(2))],
      the Nd(III) centre is located on a twofold axis and exhibits a ten-coordinated
      distorted bicapped square-anti-prismatic geometry. The pyridinium NH H atom is
      disordered over the two ligands. Adjacent mononuclear clusters are linked through
      N-H?O and N-H?N hydrogen-bonding inter-actions, generating layers in the (102)
      plane.

PMID- 22589829
TI  - Aqua-(MU-cone-26,28-dibut-oxy-25,27-bis-{N-[5-(dimethyl-amino)-naphthalene-1
      sulfon-yl]carbamoylmeth-oxy}-5,11,17,23-tetra-kis-(1,1-dimethyl-eth
      yl)calix[4]arene(2-))disodium acetonitrile tetra-solvate.
AB  - The structure of the title complex,
      [Na(2)(C(80)H(98)N(4)O(10)S(2))(H(2)O)].4CH(3)CN, obtained after crystallization
      from aceto-nitrile, contains two formula units in the asymmetric unit (Z' = 2)
      and an estimated four mol-ecules of acetonitrile per calixarene moiety. It is
      unusual for two Na(+) ions to occupy the lower rims of the cone calix[4]arene, as
      in this case, with one Na(+) ion forming two O-> Na(+) coordinate bonds with the
      two but-oxy groups and four such bonds with the two N-dansyl carboxamide groups,
      forming six dative bonds between Na(+) and O. On the other hand, the other Na(+)
      ion forms only five O->Na(+) coordinate bonds on the far end of the calix[4]arene
      lower rim, bringing the two dansyl groups in close proximity with each other.
      There also appears to be an O->Na(+) coordination coming from a dangling water
      mol-ecule. The structure contained both resolved and poorly resolved solvent mol
      ecules. The latter were treated using the SQUEEZE routine in PLATON [Spek (2009
      ?). Acta Cryst. D65, 148-155].

PMID- 22589830
TI  - Bis(guanidinium) tris-(pyridine-2,6-dicarboxyl-ato
      kappa(3)O(2),N,O(6))zirconate(II) tetra-hydrate.
AB  - In the title complex, (CH(6)N(3))(2)[Zr(C(7)H(3)NO(4))(3)].4H(2)O, the Zr(IV) ion
      lies on a twofold rotation axes and is coordinated by six O and three N atoms of
      three tridentate pyridine-2,6-dicarboxyl-ate ligands, forming a slightly
      distorted tricapped trigonal-prismatic geometry. In the crystal, O-H?O and N-H?O
      hydrogen bonds link the components into a three-dimensional network.

PMID- 22589831
TI  - Bis(6-meth-oxy-1-methyl-2,3,4,9-tetra-hydro-1H-beta-carbolin-2-ium) tetra
      chloridozincate(II) dihydrate.
AB  - The asymmetric unit of the title compound, (C(13)H(17)N(2)O)(2)[ZnCl(4)].2H(2)O,
      contains two tetra-hydro-harmine cations, one tetra-chloro-zincate(II) anion and
      two water mol-ecules. In the cations, the two 1H-indole ring systems are
      essentially planar, with maximum deviations of 0.016 (2) and 0.018 (2) A, and
      both tetra-hydro-pyridinium rings show a half-chair conformation. The Zn(II)
      complex anion has a distorted tetra-hedral geometry. In the crystal, inter
      molecular N-H?O, N-H?Cl, O-H?O, O-H?Cl and C-H?O hydrogen bonds link the
      components into a three-dimensional network. A pi-pi inter-action with a centroid
      centroid distance of 3.542 (14) A is also observed.

PMID- 22589832
TI  - Di-MU-iodido-bis-{[(R)-(+)-2,2'-bis-(di-phenyl-phosphan-yl)-1,1'-binaphthyl
      kappa(2)P,P']copper(I)} 0.67-hydrate.
AB  - The structure of the title compound, [Cu(2)I(2)(C(44)H(32)P(2))(2)].0.67H(2)O,
      has been determined because of its inter-esting catalytic and optical features.
      The mol-ecule, which has non-crystallographic C2-symmetry, consists of a core
      structure of two Cu(I) ions, bridged by two iodide ions. Each Cu(I) ion is also
      coordinated by one equivalent of the chiral bidentate (R)-BINAP ligand [BINAP =
      2,2'-bis-(diphenyl-phosphan-yl)-1,1'-binaphth-yl]. Thus, both cations show a
      distorted tetra-hedral geometry being surrounded by two I atoms and two P atoms
      from the (R)-BINAP ligands. The complex consists of isolated butterfly-shaped mol
      ecules featuring an angle of 146.11 (2) degrees  between adjacent CuI(2) planes.
      The structure displays intra-molecular C-H?I hydrogen bonding and contains
      disordered water. The absolute configuration of this chiral complex was
      determined by anomalous dispersion effects.

PMID- 22589833
TI  - [(4-Methyl-benz-yl)bis-(pyridin-2-ylmeth-yl)amine-kappa(3)N,N',N'']bis-(thio
      cyanato-kappaS)copper(II) dichloro-methane hemisolvate.
AB  - The title compound, [Cu(NCS)(2)(C(20)H(21)N(3))].0.5CH(2)Cl(2), crystallized with
      two independent complex mol-ecules (A and B) in the asymmetric unit, accompanied
      by one dichloro-methane solvent mol-ecule. Each Cu(II) atom has a square
      pyramidal geometry, being coordinated by five N atoms, three from the (4-methyl
      benz-yl)bis-(pyridin-2-ylmeth-yl)amine ligand and two from the thio-cyanate
      ligands. In the crystal, the B mol-ecules are linked via C-H?S inter-actions,
      forming chains propagating along [100].

PMID- 22589834
TI  - Bis(methacrylato-kappaO)bis-(2,4,6-trimethyl-pyridine-kappaN)copper(II).
AB  - In the monomeric title complex, [Cu(C(4)H(5)O(2))(2)(C(8)H(11)N)(2)], the Cu(II)
      atom lies on a centre of inversion. Its coordination by two substituted pyridine
      ligands and two carboxyl-ate anions leads to a slightly distorted trans
      CuN(2)O(2) square-planar geometry. The dihedral angle between the mean planes of
      the pyridine (py) ring and the carboxyl-ate group is 74.71 (7) degrees . The
      dihedral angles between the planar CuN(2)O(2) core and the py ring and carboxyl
      ate plane are 67.72 (5) and 89.95 (5) degrees , respectively. Based on the
      refined C=C and C-C bond lengths, the terminal =CH(2) and -CH(3) groups of the
      carboxyl-ate anion may be disordered, but the disorder could not be resolved in
      the present experiment. Several intra-molecular C-H?O inter-actions occur. In the
      crystal, mol-ecules are linked by weak C-H?O hydrogen bonds, generating chains
      propagating in [100].

PMID- 22589835
TI  - [meso-5,10,15,20-Tetra-kis(5-bromo-thio-phen-2-yl)porphyrinato
      kappa(4)N,N',N'',N''']nickel(II).
AB  - The Ni(II) atom in the title porphyrin complex, [Ni(C(36)H(16)Br(4)N(4)S(4))], is
      in a square-planar geometry defined by four pyrrole N atoms. There is
      considerable buckling in the porphyrin ring with the dihedral angles between the
      N(4) donor set and the pyrrole rings being in the range 17.0 (3)-18.8 (3) degrees
      . Each of the six-membered chelate rings is twisted about an Ni-N bond and the
      dihedral angles between diagonally opposite chelate rings are 13.08 (15) and
      13.45 (11) degrees ; each pair of rings is orientated in opposite directions. The
      bromo-thienyl rings are twisted out of the plane of the central N(4) core with
      dihedral angles in the range 51.7 (2)-74.65 (19) degrees . Supra-molecular chains
      along [001] are formed through C-H?Br inter-actions in the crystal packing. Three
      of the four bromo-thienyl units are disordered over two coplanar positions of
      opposite orientation with the major components being in 0.691 (3), 0.738 (3) and
      0.929 (9) fractions.

PMID- 22589836
TI  - Bis[2-(diphenyl-phosphanyl-kappaP)benzaldehyde]-iodidogold(I).
AB  - In the title compound, [AuI(C(19)H(15)OP)(2)], the complete mol-ecule is
      generated by the application of twofold symmetry. The Au(I) atom is in a trigonal
      planar geometry within an IP(2) donor set with the greatest distortion seen in
      the P-Au-P angle [128.49 (3)  degrees ]. Close intra-molecular Au?O inter-actions
      [3.172 (3) A] are observed. No specific inter-molecular inter-actions are noted
      in the crystal packing.

PMID- 22589837
TI  - Tetra-kis{2-[2-(2,6-dichloro-anilino)phen-yl]ethano-ato-kappa(2)O:O'}bis
      [(dimethyl sulfoxide-kappaO)copper(II)](Cu-Cu): a binuclear Cu(II) complex with
      the non-steroidal anti-inflammatory drug diclofenac.
AB  - The title compound, [Cu(2)(C(14)H(10)Cl(2)NO(2))(4)(C(2)H(6)OS)(2)], comprises a
      Cu(II) (2) core that is quadruply bridged by four carboxyl-ate ligands with the
      dimethyl sulfoxide ligands binding along the Cu?Cu axis. The four carboxyl-ate
      ligands bind in a bidentate syn-syn bridging mode. Mol-ecules reside on
      crystallographic inversion centres bis-ecting the mid-point of the Cu?Cu axis.
      There are no inter-molecular inter-actions of note.

PMID- 22589838
TI  - {2-[(2-Amino-cyclo-hex-yl)imino-meth-yl]phenolato}dioxidovanadium(V).
AB  - In the title dioxidovanadium complex, [V(C(13)H(17)N(2)O)O(2)], the V(V) atom is
      in a square-based pyramidal coordination: the basal plane is defined by the
      phenolate O, imine N and amine N atoms of the tridentate Schiff base ligand, and
      by one oxide O atom. The apical position is occupied by the other oxide O atom.
      In the crystal, mol-ecules are connected by N-H?O and N-H?(O,O) hydrogen bonds,
      forming a tetra-mer.

PMID- 22589839
TI  - catena-Poly[[bis-(MU(3)-5-hy-droxy-isophthalato)bis-(pyrazino-[2,3
      f][1,10]phenanthroline)dicadmium] dihydrate].
AB  - The title coordination polymer,
      {[Cd(2)(C(8)H(4)O(5))(2)(C(14)H(8)N(4))(2)].2H(2)O}(n), has a layered structure.
      The asymmetric unit contains two Cd(II) ions, two pyrazino-[2,3
      f][1,10]phenanthroline, two 5-hy-droxy-isophthalate (hip) ligands and two lattice
      water mol-ecules. Each Cd(II) ion is coordinated by two N atoms from a chelating
      pyrazino-[2,3-f][1,10]phenanthroline and four O atoms from three different hip
      ligands, resulting in a distorted CdN(2)O(4) octa-hedral coordination
      environment. The hip ligand connects adjacent Cd(II) ions, forming forming layers
      parallel to (010). Intralayer O-H?O hydrogen bonds involving the hydroxy groups
      and solvent water molecules consolidate the crystal packing.

PMID- 22589840
TI  - (Di-2-pyridyl-amine-kappa(2)N(2),N(2'))diiodidoplatinum(II).
AB  - The Pt(II) ion in the title complex, [PtI(2)(C(10)H(9)N(3))], is four-coordinated
      in a distorted square-planar environment defined by the two pyridine N atoms of
      the chelating di-2-pyridyl-amine (dpa) ligand and by two I(-) anions. The dpa
      ligand is not planar, the dihedral angle between the pyridine rings being 52.8
      (3) degrees . Pairs of complex mol-ecules are assembled through inter-molecular N
      H?I hydrogen bonds, forming a dimer-type species. The complexes are stacked in
      columns along the b axis and display several inter-molecular pi-pi inter-actions
      between the pyridine rings, with a shortest ring centroid-centroid distance of
      3.997 (5) A.

PMID- 22589841
TI  - Intra- and supra-molecular inter-actions in cis,mer-diaqua-tris-(1H-imidazole
      kappaN(3))(terephthalato-kappaO)cobalt(II) monohydrate.
AB  - In the title compound, [Co(C(8)H(4)O(4))(C(3)H(4)N(2))(3)(H(2)O)(2)].H(2)O, the
      cisoid angles are in the range 85.59 (5)-93.56 (5) degrees , while two equal
      transoid angles deviate significantly from the ideal linear angle, the third
      being almost linear. One carboxyl-ate group is almost coplanar [1.23 (13) degrees
      ] with the plane of its parent aromatic ring, although it has one O-atom donor
      involved in one coordination and one hydrogen bond as acceptor. The other
      carboxyl-ate group does not coordinate and is rotated out of this plane with a
      torsional twist of 17.27 (20) degrees . The coordination neutral entity, based on
      aqua ligands and two cyclic co-ligands seems, at first sight, monomeric. Strongly
      tight, via one intra-molecular hydrogen bond between aqua and carboxyl-ate O
      atoms, it brings out a quasi-planar six-membered ring around the Co(II) atom,
      turning the CoN(3)O(3) coordination octa-hedron into a new building block. The
      rigidity of this feature associated with several hydrogen-bonded arrays yields an
      extended structure. In the resulting supra-molecular packing, a binuclear
      hydrated Co(II) assembly, built up from triple strands driven by different
      heterosynthons, embodies the synergy of coordination, covalent and hydrogen
      bonds.

PMID- 22589842
TI  - (Acetyl-acetonato-kappa(2)O,O')[(2-bromo-phen-yl)diphenyl-phosphane
      kappaP]carbonyl-rhodium(I).
AB  - In the title compound, [Rh(C(5)H(7)O(2))(C(18)H(14)BrP)(CO)], the Rh(I) atom
      adopts a slightly distorted square-planar geometry involving two O atoms [Rh-O =
      2.077 (2) and 2.033 (2) A] of the acetyl-acetonate ligand, one carbonyl C atom
      [Rh-C = 1.813 (2) A] and one P atom [Rh-P = 2.242 (5) A] of the PPh(2)(2
      BrC(6)H(4)) phosphane ligand. Difference electron density maps indicate a
      disorder of the Br atom over two positions in an approximate 0.95:0.05 ratio.
      However, this disorder could not be resolved satisfactorily with the present
      data.

PMID- 22589843
TI  - trans-Bis(5-amino-1,3,4-thia-diazol-2-thio-lato-kappaS(2))bis-(triphenyl
      phosphane-kappaP)palladium(II) dimethyl sulfoxide disolvate hemihydrate.
AB  - The title complex,
      [Pd(C(2)H(2)N(3)S(2))(2)(C(18)H(15)P)(2)].2C(2)H(6)OS.0.5H(2)O, was obtained from
      the reaction of trans-[(Ph(3)P)(2)PdCl(2)] with 5-amino-1,3,4-thia-diazole-2
      thione (SSNH(2)) in a 2:1 molar ratio. The Pd(II) atom, located in a
      crystallographic center of symmetry, has a square-planar geometry with two
      triphenyl-phosphine P-coordinated mol-ecules and two SSNH(2) ligands with the S
      atoms in a trans conformation. The latter ligand exhibits N-H?N hydrogen-bonding
      contacts formed by the amino group with the thia-diazole ring, generating a chain
      along the c axis. The asymmetric unit contains one half of the complex mol-ecule
      along with disordered dimethyl sulfoxide and water mol-ecules.

PMID- 22589844
TI  - Dichlorido(pyridine-kappaN)[2-(pyridinium-1-yl)acetato-kappaO]zinc(II).
AB  - In the title complex, [ZnCl(2)(C(5)H(5)N)(C(7)H(7)NO(2))], the Zn(II) atom adopts
      a distorted tetra-hedral coordination geometry [the smallest angle being 105.22
      (15) degrees  and the widest angle being 115.60 (16) degrees ] that is formed
      from one monodentate carboxyl-ate ligand, one pyridine ligand and two Cl atoms.

PMID- 22589845
TI  - Tetra-aqua-bis-[4-(1H-imidazol-1-yl-kappaN(3))benzoato]cobalt(II).
AB  - In the title compound, [Co(C(10)H(7)N(2)O(2))(2)(H(2)O)(4)], the Co(II) atom lies
      on an inversion centre and displays a slightly distorted octa-hedral geometry.
      The coordination sphere is defined by two mutually trans N atoms from two 4
      (imidazol-1-yl)benzoate ligands and the O atoms from four water mol-ecules. The
      crystal structure is stabilized by O-H?O hydrogen bonds.

PMID- 22589846
TI  - Dicarbonyl-{3,3'-di-tert-butyl-5,5'-di-meth-oxy-2,2'-bis-[(4,4,5,5-tetra-phenyl
      1,3,2-dioxa-phospho-lan-2-yl)-oxy-kappaP]biphen-yl}hydridorhodium(I) diethyl
      ether monosolvate.
AB  - In the title compound, [Rh(C(74)H(68)O(8)P(2))H(CO)(2)].C(4)H(10)O, the C(2)HP(2)
      coordination set at the Rh(I) ion is arranged in a distorted trigonal-planar
      geometry with one P atom of the diphosphite mol-ecule and the H atom adopting the
      axial coordination sites.

PMID- 22589847
TI  - Redetermination of (d-penicillaminato)lead(II).
AB  - In the title coordination polymer, [Pb(C(5)H(9)NO(2)S)](n) {systematic name:
      catena-poly[(MU-2-amino-3-methyl-3-sulfido-butano-ato)lead(II)]}, the d
      penicillaminate ligand coordin-ates to the metal ion in an N,S,O-tridentate mode.
      The S atom acts as a bridge to two neighbouring Pb(II) ions, thereby forming a
      double thiol-ate chain. Moreover, the coordinating carboxyl-ate O atom forms
      bridges to the Pb(II) ions in the adjacent chain. The overall coordination sphere
      of the Pb(II) ion can be described as a highly distorted penta-gonal bipyramid
      with a void in the equatorial plane between the long Pb-S bonds probably occupied
      by the stereochemically active inert electron pair. The amino H atoms form N-H?S
      and N-H?O hydrogen bonds, resulting in a cluster of four complex units, giving
      rise to an R(4) (4)(16) ring lying in the ab plane. The crystal structure of the
      title compound has been reported previously [Freeman et al. (1974 ?). Chem. Soc.
      Chem. Commun. pp. 366-367] but the atomic coordinates have not been deposited in
      the Cambridge Structural Database (refcode DPENPB). Additional details of the
      hydrogen bonding are presented here.

PMID- 22589848
TI  - cis-Dichloridobis(quinoline-kappaN)-platinum(II) nitro-methane monosolvate.
AB  - In the title compound, [PtCl(2)(C(9)H(7)N)(2)].CH(3)NO(2), the Pt(II) cation is
      four-coordinated in an essentially square-planar environment by two N atoms from
      two quinoline ligands and two Cl(-) anions. One of the nearly planar quinoline
      ligands [maximum deviations = 0.042 (6) and 0.018 (7) A] is almost perpendicular
      to the PtCl(2)N(2) unit [maximum deviation = 0.024 (3) A], making a dihedral
      angle of 89.6 (1) degrees , whereas the other is slightly inclined to the central
      plane with a dihedral angle of 74.1 (1) degrees . The dihedral angle between the
      quinoline ligands is 88.3 (2) degrees . In the crystal, each solvent mol-ecule is
      linked to the metal complex by weak inter-molecular C-H?O hydrogen bonds.

PMID- 22589849
TI  - Penta-aqua-(4,6-dihy-droxy-benzene-1,3-disulfonato-kappaO(1))zinc penta-hydrate.
AB  - The Zn(II) atom in the title complex, [Zn(C(6)H(4)O(8)S(2))(H(2)O)(5)].5H(2)O, is
      coordinated by five water mol-ecules and an O atom of a 4,6-dihy-droxy-benzene
      1,3-disulfonate dianion. The coord-ination geometry is distorted octa-hedral,
      with the Zn-O(sulfonate) bond relatively long compared to the Zn-O(water) bonds.
      The coordinated and lattice water mol-ecules inter-act with each other and with
      the hy-droxy groups and sulfonate ligand through O-H?O hydrogen bonds, generating
      a tightly held three-dimensional network.

PMID- 22589850
TI  - cis-(Nitrato-kappa(2)O,O')(2,5,5,7,9,12,12,14-octa-methyl-1,4,8,11-tetra-aza
      cyclo-tetra-decane-kappa(4)N,N',N'',N''')cadmium nitrate hemihydrate.
AB  - The Cd(II) atom in the title complex, [Cd(NO(3))(C(18)H(40)N(4))]NO(3).0.5H(2)O,
      is coordinated within a cis-N(4)O(2) donor set provided by the tetra-dentate
      macrocyclic ligand and two O atoms of a nitrate anion; the coordination geometry
      is distorted octa-hedral. The lattice water mol-ecule is located on a twofold
      rotation axis. N-H?O hydrogen bonds and weak C-H?O inter-actions link the complex
      cations into a supra-molecular layer in the bc plane. Layers are connected by O
      H?O hydrogen bonds between the lattice water mol-ecule and the non-coordinating
      nitrate anion, as well as by weak C-H?O contacts.

PMID- 22589851
TI  - Poly[hydrazin-1-ium [diaqua-bis-(MU(4)-pyridazine-3,6-dicarboxyl-ato)trilithate]
      monohydrate].
AB  - The structure of the title compound,
      {(N(2)H(5))[Li(3)(C(6)H(2)N(2)O(4))(2)(H(2)O)(2)].H(2)O}(n), is composed of mol
      ecular dimers, each built up of two symmetry-related Li(I) ions with distorted
      trigonal-bipyramidal coordinations bridged by two deprotonated ligand mol-ecules
      via their N,O-bonding sites. Doubly solvated Li(I) ions with a distorted tetra
      hedral geometry link adjacent dimers, forming a polymer generated by bridging
      bidentate carboxyl-ato O atoms to Li(I) ions in adjacent dimers, forming anionic
      layers parallel to the ac plane with monoprotonated hydrazinium cations and
      crystal water mol-ecules positioned between them. The layers are held together by
      an extended system of hydrogen bonds in which the hydrazinium cations and
      coordinated and crystal water mol-ecules act as donors and carboxyl-ate O atoms
      act as acceptors.

PMID- 22589852
TI  - Disorder in the anionic part of catena-poly[[(pyrazine-2-carboxyl-ato)copper(II)]
      MU-pyrazine-2-carboxyl-ato].
AB  - The title compound, [Cu(C(5)H(3)N(2)O(2))(0.88)(C(6)H(4)NO(2))(1.12)](n), is
      characterized by disorder of the anion, resulting from a statistical occupation
      in a 0.44 (3):0.56 (3) ratio of pyrazine-2-carboxylate and pyridine-2
      carboxylate. The compound was isolated during attempts to synthesize a mixed
      ligand coordination polymer by solvothermal reaction between copper(II) nitrate
      and equimolar mixtures of pyrazine-2-carboxylic acid and pyridine-2-carb-oxy-lic
      acid in a mixture of water and EtOH. The difference in the two components of the
      compound is due to substitutional disorder of a CH group for one of the N atoms
      of the pyrazine ring which share the same site in the structure. In the crystal
      structure, the Cu(II) atom lies on an inversion centre and is six-coordinated in
      a distorted N(2)O(4) geometry. The carboxyl-ate group carbonyl O atoms are weakly
      coordinated to an equivalent Cu(II) atom that is translated one unit cell in the
      a-axis direction, thus forming a polymeric chain through carboxyl-ate bridges.

PMID- 22589853
TI  - catena-Poly[(triaqua-zinc)-MU-furan-2,5-dicarboxyl-ato-kappa(3)O(2):O(2),O(2')].
AB  - In the crystal structure of the title compound, [Zn(C(6)H(2)O(5))(H(2)O)(3)](n),
      an infinite chain is formed along [001] by linking of the Zn(H(2)O)(3) entities
      with one carboxyl-ate group of the furan-2,5-dicarboxyl-ate ligand. Adjacent
      chains are linked by O(water)-H?O hydrogen-bonding inter-actions. The
      Zn(H(2)O)(3)O(3) polyhedron displays a distorted octa-hedral geometry with one
      weak Zn-O(carboxyl-ate) coordination [2.433 (8) A degrees ] and two water mol
      ecules located in axial positions. Except for one of the axial water molecules
      and two adjacent H atoms, the other atoms (including H atoms) possess site
      symmetry m.

PMID- 22589854
TI  - Bis(dipyridin-2-yl-amine-kappa(2)N(2),N(2'))palladium(II) dinitrate.
AB  - The asymmetric unit of the title compound, [Pd(C(10)H(9)N(3))(2)](NO(3))(2),
      contains one half of a cationic Pd(II) complex and one NO(3) (-) anion. In the
      complex, the Pd(II) ion is four-coordinated by four pyridine N atoms derived from
      the two chelating dipyridin-2-yl-amine (dpa) ligands. The Pd(II) atom is located
      on an inversion centre, and thus the PdN(4) unit is exactly planar. The dpa
      ligand itself is not planar, showing a dihedral angle between the pyridine rings
      of 39.9 (1) degrees . The anions are connected to the complex by inter-molecular
      N-H?O hydrogen bonds between the two O atoms of the anion and the N-H group of
      the cation. Weak inter-molecular C-H?O hydrogen bonds additionally link the
      constituents in the crystal structure. The NO(3) (-) anion was found to be
      disordered over two sites with a site-occupancy factor of 0.55 (10) for the major
      component.

PMID- 22589856
TI  - Di-MU-methano-lato-kappa(4)O:O-bis-[bis-(3-methyl-5-phenyl-1H-pyrazole
      kappaN(2))(nitrato-kappaO)copper(II)].
AB  - Copper nitrate in methanol solution cleaves the N-C(methanol) bond when reacted
      with 3-methyl-5-phenyl-pyrazole-1-methanol to yield the centrosymmetric dinuclear
      title compound, [Cu(2)(CH(3)O)(2)(NO(3))(2)(C(10)H(10)N(2))(4)], in which the
      Cu(II) atom is linked to a nitrate ion, two methano-late ions and two pyrazole
      ligands in a distorted square-pyramidal environment. The O atom of the nitrate
      anion occupies the apical site. The crystal structure features intra-molecular N
      H?O hydrogen bonds.

PMID- 22589855
TI  - Bis(acetato-kappaO)(di-2-pyridyl-amine-kappa(2)N(2),N(2'))palladium(II).
AB  - In the title complex, [Pd(CH(3)COO)(2)(C(10)H(9)N(3))], the Pd(II) ion is four
      coordinated in a slightly distorted square-planar environment by two pyridine N
      atoms of the chelating di-2-pyridyl-amine (dpa) ligand and two O atoms from two
      anionic acetate ligands. The dpa ligand coordinates the Pd(II) atom in a boat
      conformation of the resulting chelate ring; the dihedral angle between the
      pyridine rings is 39.3 (2) degrees . The two acetate anions coordinate the Pd(II)
      atom as monodentate ligands and are located on the same sides of the PdN(2)O(2)
      unit plane. The carboxyl-ate groups of the anionic ligands appear to be
      delocalized on the basis of the C-O bond lengths. Two complex mol-ecules are
      assembled through inter-molecular N-H?O hydrogen bonds, forming a dimer-type
      species. Inter-molecular C-H?O hydrogen bonds further stabilize the crystal
      structure.

PMID- 22589857
TI  - Bis(2-{[(9H-fluoren-2-yl)methyl-idene]amino}-phenolato-kappa(2)N,O)zinc methanol
      disolvate.
AB  - In the title compound, [Zn(C(20)H(14)NO)(2)].2CH(3)OH, the Zn(II) atom lies on a
      crystallographic twofold rotation axis and is coordinated by two O atoms and two
      N atoms from two bidentate 2-{[(9H-fluoren-2-yl)methyl-idene]amino}-phenolate
      ligands within a distorted tetra-hedral geometry. The dihedral angle between the
      two chelate rings is 82.92 (5) degrees . In the coordinated ligand, the phenol
      ring is twisted at 30.22 (9) degrees  from the mean plane of the fluorene ring.
      In the crystal, O-H?O hydrogen bonds link the complex mol-ecules to the methanol
      solvent mol-ecules.

PMID- 22589858
TI  - Diaqua-bis-(benzoato-kappaO)bis-[4,4,5,5-tetra-methyl-2-(pyridin-4-yl
      kappaN)imidazoline-1-oxyl 3-oxide]cobalt(II).
AB  - The title compound, [Co(C(7)H(5)O(2))(2)(C(12)H(16)N(3)O(2))(2)(H(2)O)(2)], was
      obtained from a conventional solvent evaporation method. The complex mol-ecule is
      centrosymmetric, so pairs of equivalent ligands lie trans to each other in a
      slightly distorted octa-hedral CoN(2)O(4) geometry. The Co(II) ion is coordinated
      by the pyridine N atoms from NITpPy ligands [NITpPy is 4,4,5,5-tetra-methyl-2
      (pyridin-4-yl)imidazoline-1-oxyl 3-oxide), water O atoms and two monodentate
      benzoate O atoms. The complex mol-ecules are connected by O-H?O hydrogen bonds
      between water mol-ecules and benzoate ligands, forming chains parallel to [100].
      pi-pi stacking inter-actions between the benzoate ligands with centroid-centroid
      distances of 3.752 (2) A connect the chains into layers parallel to (10-1).

PMID- 22589859
TI  - trans-Dichloridobis(triphenyl-phosphane-kappaP)palladium(II) benzene hemisolvate.
AB  - The title complex, [PdCl(2)(C(18)H(15)P)(2)].0.5C(6)H(6), has the Pd(II) ion in a
      square-planar coordination mode (r.m.s. deviation for Pd, P and Cl atoms = 0.024
      A) with the PPh(3) and Cl ligands mutually trans. The benzene solvent mol-ecule
      is located about a crystallographic inversion centre. The title complex is
      isostructural with trans-dichloridobis(triphenyl-phosphane)-palladium(II) 1,4
      dichloro-benzene sesquisolvate [Kitano et al. (1983 ?). Acta Cryst. C39, 1015
      1017].

PMID- 22589860
TI  - Dichlorido(ethanol-kappaO)[2-(1,3-thia-zol-4-yl-kappaN)-1H-benzimidazole
      kappaN(3)]copper(II).
AB  - In the title complex, [CuCl(2)(C(10)H(7)N(3)S)(C(2)H(5)OH)], the Cu(II) ion is
      five-coordinated in a distorted square-pyramidal geometry by two N atoms from a 2
      (1,3-thia-zol-4-yl)-1H-benzimidazole ligand, one O atom from an ethanol mol-ecule
      and two Cl atoms. In the crystal, O-H?Cl and N-H?Cl hydrogen bonds link the
      complex mol-ecules into a layer parallel to (100). pi-pi inter-actions between
      the thia-zole rings are observed [centroid-centroid distance = 3.749 (3) A].

PMID- 22589861
TI  - (Acetyl-acetonato-kappa(2)O,O')carbon-yl[tris-(4-chloro-phen-yl)phosphane
      kappaP]rhodium(I).
AB  - The title compound, [Rh(C(5)H(7)O(2))(C(18)H(12)Cl(3)P)(CO)], contains the
      bidentate acetyl-acetonate ligand coordinated to the Rh(I) atom, forming a
      chelate ring [Rh-O = 2.0327 (15) and 2.0613 (14) A]. The Rh(I) atom is
      additionally coordinated by one P [Rh-P = 2.2281 (6) A] and one carbonyl C [Rh-C
      = 1.812 (2) A] atom, resulting in a slightly distorted square-planar geometry.
      The mol-ecules are packed to minimize steric hindrance with the phosphanes
      positioned above and below the slightly distorted square geometrical plane.

PMID- 22589862
TI  - trans-Bis[(2-bromo-phen-yl)diphenyl-phosphane-kappaP]carbonyl-chlorido
      rhodium(I).
AB  - The title compound, trans-[RhCl(C(18)H(14)BrP)(2)(CO)], has a slightly disordered
      square-planar geometry with the Rh ion(I) situated on an inversion the centre and
      carbon-yl-chloride disorder observed as a result of the crystallographic
      inversion symmetry. Selected geometric parameters include: Rh-P = 2.3430 (8) A,
      Rh-Cl = 2.434 (3) A, Rh-C = 1.722 (8) A, P-Rh-P = 180.00 (3) degrees , P-Rh-Cl =
      95.40 (7) degrees , 84.60 (7) degrees  and Rh-C-O = 177.9 (8) degrees .

PMID- 22589863
TI  - Bis{MU-2-[3-carboxyl-atometh-yl-4-(phenyl-sulfan-yl)phen-yl]propano-ato
      kappa(4)O,O':O'',O'''}bis-[(2,2'-bipyridine-kappa(2)N,N')cadmium].
AB  - In the title complex, [Cd(2)(C(17)H(14)O(4)S)(2)(C(10)H(8)N(2))(2)], which was
      hydro-thermally synthesized, the Cd(II) cation is hexa-coordinated in a distorted
      octa-hedral geometry by two N atoms from a 2,2'-bipyridine ligand and by four O
      atoms from two different 2-[3-carboxyl-atometh-yl-4-(phenyl-sulfan-yl)phen
      yl]propano-ate ligands, forming a cyclic dimetallic complex.

PMID- 22589864
TI  - Diaqua-bis-(pyrazine-2-carboxamide-kappa(2)N(1),O)cobalt(II) dinitrate.
AB  - The asymmetric unit of the title complex,
      [Co(C(5)H(5)N(3)O)(2)(H(2)O)(2)](NO(3))(2), contains one half of a Co(II)
      cationic unit and a nitrate anion. The entire
      [Co(C(5)H(5)N(3)O)(2)(H(2)O)(2)](2+) cationic unit is completed by the
      application of inversion symmetry at the Co(II) site, generating a six-coordinate
      distorted octa-hedral environment for the metal ion. The chelating pyrazine-2
      carboxamide mol-ecules are bound to cobalt via N and O atoms, forming a square
      plane, while the remaining two trans positions in the octa-hedron are occupied by
      two coordinated water mol-ecules.

PMID- 22589865
TI  - {5,5'-Dimeth-oxy-2,2'-[2,2-dimethyl-propane-1,3-diylbis(nitrilo-methanylyl
      idene)]diphenolato}palladium(II).
AB  - In the title compound, [Pd(C(21)H(24)N(2)O(4))], the complete mol-ecule is
      generated by crystallographic mirror symmetry with the Pd and three C atoms lying
      on the mirror plane. The Pd-O and Pd-N distances are 1.9932 (6) and 2.0029 (7) A,
      respectively. The dihedral angle between two benzene rings of the ligand is 79.21
      (4) degrees . In the crystal, C-H?O hydrogen bonds link the mol-ecules into
      layers parallel to the ab plane. These planes are further connected by C-H?O
      inter-actions, forming a three-dimensional network.

PMID- 22589866
TI  - catena-Poly[[bis-(pyridine-3-carb-oxy-lic acid-kappaN)mercury(II)]-di-MU
      chlorido].
AB  - In the title compound, [HgCl(2)(C(6)H(5)NO(2))(2)](n), the Hg(II) cation is
      located on an inversion center and is six-coordinated in a distorted octa-hedral
      geometry by two N atoms from two pyridine-3-carb-oxy-lic acid mol-ecules and four
      bridging Cl(-) anions. The bridging function of the Cl(-) anions leads to
      polymeric chains running along the a axis. One Hg-Cl bond is much longer than the
      other. In the crystal, O-H?O and weak C-H?Cl hydrogen bonds are observed.

PMID- 22589867
TI  - Aqua-(2,2'-bipyridine-kappa(2)N,N'){(E)-[(5-chloro-2-oxidobenzyl-idene)amino
      kappa(2)N,O]methane-sulfonato-kappaO}zinc.
AB  - In the title compound, [Zn(C(8)H(6)ClNO(4)S)(C(10)H(8)N(2))(H(2)O)], the Zn(II)
      atom is six-coordinated by two O atoms and one N atom from a tridentate Schiff
      base ligand and two N atoms from a chelating 2,2'-bipyridine ligand and one water
      mol-ecule, forming a slightly distorted octa-hedral geometry. In the crystal, O
      H?O hydrogen bonds link pairs of complex mol-ecules into dimers. An intra
      molecular O-H?O hydrogen bond is also present.

PMID- 22589868
TI  - Bis(di-2-pyridyl-amine-kappa(2)N(2),N(2'))platinum(II) dibromide monohydrate.
AB  - The asymmetric unit of the title compound, [Pt(C(10)H(9)N(3))(2)]Br(2).H(2)O,
      contains two crystallographically independent half-mol-ecules of the cationic
      Pt(II) complex, two Br(-) anions and a lattice water mol-ecule; an inversion
      centre is located at the centroid of each complex. Each Pt(II) ion is four
      coordinated in an essentially square-planar environment by four pyridine N atoms
      derived from the two chelating di-2-pyridyl-amine (dpa) ligands, and the PtN(4)
      unit is exactly planar. The chelate ring formed by the dpa ligand displays a boat
      conformation, with dihedral angles between the pyridine rings of 35.9 (2) and
      41.0 (2) degrees . The complex cations, Br(-) anions and solvent water mol-ecules
      are linked by O-H?Br, N-H?Br, C-H?O and C-H?Br hydrogen bonds, forming a three
      dimensional network.

PMID- 22589869
TI  - Bis(azido-kappaN)(di-2-pyridyl-amine-kappa(2)N(2),N(2'))palladium(II).
AB  - In the title complex, [Pd(N(3))(2)(C(10)H(9)N(3))], the Pd(II) ion is in a
      slightly distorted square-planar coordination environment. The ligator atoms
      comprise the two pyridine N atoms of the chelating di-2-pyridyl-amine (dpa)
      ligand and two N atoms from two azide anions. The dpa ligand coordinates the Pd
      atom in a boat conformation, the dihedral angle between the pyridine rings being
      24.4 (1) degrees . The pyridine rings are somewhat inclined to the least-squares
      plane of the PdN(4) unit, making dihedral angles of 29.02 (9) and 26.47 (9)
      degrees . The azide ligands are slightly bent, with N-N-N angles of 173.0 (4) and
      174.2 (4) degrees . In the crystal, mol-ecules are connected by N-H?N and C-H?N
      hydrogen bonds, forming chains along the c axis. When viewed down the b axis,
      successive chains are stacked in opposite directions. Intra-molecular C-H?N
      hydrogen bonds are also observed.

PMID- 22589870
TI  - catena-Poly[(chloridozinc)-MU-5-(1-methyl-1H-benzimidazol-2-yl-kappaN(3))-1,2,3
      triazol-1-ido-kappa(2)N(1):N(3)].
AB  - In the title complex, [Zn(C(10)H(8)N(5))Cl](n), the Zn(II) ion is four
      coordinated by one Cl atom and three N atoms from two in situ-generated
      deprotonated 5-(1-methyl-1H-benzimidazol-2-yl-kappaN(3))-1,2,3-triazol-1-ide
      ligands in a slightly distorted tetra-hedral geometry. The Zn(II) ions are
      bridged by the ligands, forming a helical chain along [001]. C-H?N and C-H?Cl
      hydrogen bonds and pi-pi inter-actions between the imidazole rings [centroid
      centroid distance = 3.4244 (10) A] assemble the chains into a three-dimensional
      supra-molecular network.

PMID- 22589871
TI  - Diaqua-bis-(2-iodo-benzoato-kappaO)bis-(nicotinamide-kappaN(1))cobalt(II).
AB  - In the title complex, [Co(C(7)H(4)IO(2))(2)(C(6)H(6)N(2)O)(2)(H(2)O)(2)], the
      Co(II) cation is located on an inversion center and is coordinated by two
      monodentate 2-iodo-benzoate (IB) anions, two nicotin-amide (NA) ligands and two
      water mol-ecules. The four O atoms in the equatorial plane around the Co(II)
      cation form a slightly distorted square-planar arrangement, while the slightly
      distorted octa-hedral coordination is completed by the two N atoms of the NA
      ligands in the axial positions. The dihedral angle between the carboxyl-ate group
      and the adjacent benzene ring is 22.3 (3) degrees , while the pyridine ring and
      the benzene ring are oriented at a dihedral angle of 84.59 (13) degrees . Intra
      molecular O-H?O hydrogen bonding occurs between the carboxyl-ate group and
      coordinated water mol-ecule. In the crystal, N-H?O, O-H?O and weak C-H?O hydrogen
      bonds link the mol-ecules into a three-dimensional supra-molecular network.

PMID- 22589872
TI  - catena-Poly[(diaqua-strontium)-bis-{MU-5-[4-(1H-imidazol-1-yl)phen-yl]tetra
      zolido}].
AB  - In the title complex polymer, [Sr(C(10)H(7)N(6))(2)(H(2)O)(2)](n), the Sr(II)
      atom lies on an inversion centre and is coordinated by four N atoms from two
      bidentate bridging trans-related 5-[4-(1H-imidazol-1-yl)phen-yl]tetra-zolide
      ligands [Sr-N = 2.387 (4) A for the tetrazolide moiety and Sr-N = 2.273 (5) A for
      the imidazole moiety], and by two O atoms from water mol-ecules [Sr-O = 2.464 (4)
      A], giving a distorted octa-hedral coordination. Pairs of ligand bridges link the
      complex units, forming chains which extend along [111] and are inter-associated
      through O(water)-H?N hydrogen bonds, giving a two-dimensional network structure
      parallel to (001). Weak pi-pi stacking inter-actions between the benzene and
      imidazole rings are also present [minimum ring centroid separation = 3.691 (4)
      A].

PMID- 22589873
TI  - cis-(Acetato-kappa(2)O,O')(5,5,7,12,12,14-hexa-methyl-1,4,8,11-tetra-aza-cyclo
      tetra-decane-kappa(4)N,N',N'',N''')nickel(II) perchlorate monohydrate.
AB  - The complete cation in the title hydrated mol-ecular salt,
      [Ni(CH(3)CO(2))(C(16)H(36)N(4))]ClO(4).H(2)O, is generated by the application of
      crystallographic twofold symmetry; the perchlorate anion and water mol-ecule are
      each disordered around a twofold axis. The Ni(II) atom exists within a cis
      N(4)O(2) donor set based on a strongly distorted octa-hedron and defined by the
      four N atoms of the macrocyclic ligand and two O atoms of a symmetrically
      coordinating acetate ligand. In the crystal, hydrogen bonding (water
      acetate/perchlorate O-H?O and amine-perchlorate N-H?O) leads to layers in the ab
      plane. The layers stack along the c axis, being connected by C-H?O(water) inter
      actions. The crystal studied was found to be a non-merohedral twin; the minor
      component refined to 15.9 (6)%.

PMID- 22589874
TI  - Dibromidobis(pyrazine-2-carboxamide-kappaN(4))zinc.
AB  - The title complex, [ZnBr(2)(C(5)H(5)N(3)O)(2)], shows crystallographic mirror
      symmetry with the Zn atom and the two bromine ligands located on the mirror
      plane. The Zn atom is four-coordinated in a distorted tetra-hedral fashion by two
      N atoms from two pyrazine-2-carboxamide ligands and two Br atoms. Only one of the
      amino H atoms is involved in an N-H?O hydrogen bond. The crystal packing is
      further stabilized by weak N-H?N and C-H?O inter-actions.

PMID- 22589875
TI  - Di-MU-benzoato-kappa(3)O,O':O;kappa(3)O:O,O'-bis-[aqua-(nitrato-kappaO)(1,10
      phenanthroline-kappa(2)N,N')lead(II)].
AB  - The title compound,
      [Pb(2)(C(7)H(5)O(2))(2)(NO(3))(2)(C(12)H(8)N(2))(2)(H(2)O)(2)], crystallizes as a
      dinuclear centrosymmetric dimer containing two Pb(II) atoms bridged by two
      benzoate ligands. Each Pb(II) atom is seven-coordinated by a water mol-ecule, a
      nitrate anion, a 1,10-phenanthroline (phen) ligand and two benzoate anions. The
      crystal packing is stabilized by O-H?O hydrogen bonds and by pi-pi stacking
      between neighboring phen ligands, with a centroid-centroid distance of 3.557 (3)
      A.

PMID- 22589876
TI  - 2-Amino-4-(4-chloro-phen-yl)-6-(pyrrolidin-1-yl)pyridine-3,5-dicarbonitrile.
AB  - In the title compound, C(17)H(14)ClN(5), two C atoms and their attached H atoms
      of the pyrrolidine ring are disordered over two sets of sites with an occupancy
      ratio of 0.638 (10):0.362 (10). The benzene and pyridine rings are inclined to
      one another by 60.57 (8) degrees . In the crystal, the amino group forms an N-H?N
      hydrogen bond with one of the cyano groups, linking the mol-ecules into chains
      along [010].

PMID- 22589877
TI  - 5-Bromo-4-iodo-2-methyl-aniline.
AB  - The asymmetric unit of the title compound, C(7)H(7)BrIN, contains two independent
      mol-ecules, which are linked by weak N-H?N hydro-den-bonding inter-actions
      between the amino groups.

PMID- 22589878
TI  - (E)-N'-(4-Isopropyl-benzyl-idene)isonicotinohydrazide monohydrate.
AB  - In the title compound, C(16)H(17)N(3)O.H(2)O, the isonicotinohydrazide mol-ecule
      adopts an E conformation about the central C=N double bond. The dihedral angle
      between the pyridine and the benzene rings is 54.56 (15) degrees . In the
      crystal, mol-ecules are connected via N-H?O, O-H?N and O-H?O hydrogen bonds,
      forming a three-dimensional network.

PMID- 22589879
TI  - 2,2,2-Trifluoro-N-(4-methyl-2-oxo-2H-chromen-7-yl)acetamide.
AB  - In the title mol-ecule, C(12)H(8)F(3)NO(3), the trifluoro-methyl group is
      rotationally disordered over three orientations in a 0.5:0.3:0.2 ratio. In the
      crystal, N-H?O hydrogen bonds link the mol-ecules related by translation into
      chains along the c axis. The crystal packing exhibits pi-pi inter-actions between
      the pyran rings of neighboring mol-ecules [centroid-centroid distance = 3.462 (4)
      A] and short C?O contacts of 3.149 (4) A.

PMID- 22589880
TI  - Fluphenazine dihydro-chloride dimethanol solvate.
AB  - In the title compound {systematic name: 1-(2-hy-droxy-eth-yl)-4-[3-(2-trifluoro
      methyl-10H-phenothia-zin-10-yl)prop-yl]piperazine-1,4-diium dichloride dimethanol
      disolvate}, C(22)H(28)F(3)N(3)OS(2+).2Cl(-).2CH(3)OH, the dihedral angle between
      the planes of the two outer benzene rings of the tricyclic phenothia-zine system
      is 46.91 (13) degrees . The piperazine ring adopts a chair conformation. The
      crystal structure is stabilized by O-H?Cl, N-H?Cl, C-H?O, C-H?Cl and C-H?F
      hydrogen bonds and contacts.

PMID- 22589881
TI  - 3-(3-Meth-oxy-benzyl-idene)chroman-4-one.
AB  - In the title compound, C(17)H(14)O(3), the dihedral angle between the meth-oxy
      benzene unit and the benzene ring of the chromanone system is 64.12 (3) degrees .
      The crystal structure is stabilized by weak C-H?O inter-actions.

PMID- 22589882
TI  - 5-{2-(4-Chloro-phen-yl)-1-[2-(4-chloro-phen-yl)-1-(3,4,5-trimeth-oxy-phen-yl)eth
      oxy]eth-yl}-1,2,3-trimeth-oxy-benzene.
AB  - The title compound, C(34)H(36)Cl(2)O(7), is a by-product from the reaction of 4
      chloro-benzyl-zinc chloride with 3,4,5-trimeth-oxy-benzaldehyde. In each of the
      two 1,2-diphenyl-ethyl moieties, the two benzene rings are arranged in a trans
      conformation and make C(ar)-C-C-C(ar) torsion angles of 163.64 (19) and 174.43
      (18) degrees . The crystal structure is stabilized by van der Waals inter-actions
      only.

PMID- 22589883
TI  - 4-[(3-Meth-oxy-anilino)methyl-idene]-2-phenyl-1,3-oxazol-5(4H)-one.
AB  - In the title compound, C(17)H(14)N(2)O(3), the oxazolone ring is essentially
      planar [maximum deviation = 0.004 (1) A] and is oriented with respect to the
      phenyl and benzene rings at 10.06 (9) and 5.63 (8) degrees , respectively; the
      dihedral angle between the phenyl ring and the benzene ring is 15.69 (8) degrees
      . In the crystal, N-H?O hydrogen bonds link the mol-ecules into chains running
      along the a axis. Neighbouring chains are inter-connected by pi-pi stacking, the
      centroid-centroid distance being 3.6201 (9) A.

PMID- 22589884
TI  - N-(2-Formyl-phen-yl)-4-toluene-sulfonamide: a second monoclinic polymorph.
AB  - The title compound, C(14)H(13)NO(3)S, (I), is a second monoclinic polymorph. The
      original polymorph, (II), was reported by Mahia et al. [Acta Cryst. (1999), C55,
      2158-2160]. Polymorph (II) crystalllized in the space group P2(1)/c (Z = 4),
      whereas the title polymorph (I) occurs in the space group P2(1)/n (Z = 4). The
      dihedral angle between the two aromatic rings is 75.9 (1) degrees  in (I)
      compared to 81.9 (1) degrees  for (II). In both polymorphs, two S(6) rings are
      generated by intra-molecular N-H?O and C-H?O hydrogen bonds, resulting in similar
      mol-ecular geometries. However, the two polymorphs differ concerning their
      crystal packing. In (I), mol-ecules are linked into C(8) zigzag chains along the
      b axis by C-H?O hydrogen bonds, whereas in (II) mol-ecules are linked by C-H?O
      hydrogen bonds, forming C(7) chains along the b axis. The title polymorph is
      further stabilized by inter-molecular C-H?pi and pi-pi inter-actions [centroid
      centroid distance = 3.814 (1) A]. These inter-actions are not evident in
      polymorph (II).

PMID- 22589885
TI  - Chlordiazepoxide dichloro-methane monosolvate.
AB  - IN THE TITLE COMPOUND (SYSTEMATIC NAME: 7-chloro-2-methyl-amino-5-phenyl-3H-1,4
      benzodiazepine 4-oxide dichloro-meth-ane monosolvate),
      C(16)H(14)ClN(3)O.CH(2)Cl(2), the seven-membered ring adopts a boat conformation
      with the CH(2) group as the prow and the two aromatic C atoms as the stern. The
      dihedral angle between the benzene rings is 75.25 (6) degrees . The crystal
      structure features centrosymmetric pairs of chlordiazepoxide mol-ecules linked by
      pairs of N-H?O hydrogen bonds, which generate R(2) (2)(12) loops.

PMID- 22589886
TI  - 2-Trifluoro-methyl-1H-benzimidazol-3-ium nitrate.
AB  - Ihe title salt, C(8)H(6)F(3)N(2) (+).NO(3) (-), the F atoms of the
      triflouromethyl group are disordered over two sets of sites in a 0.58 (2):0.42
      (2) ratio. In the crystal, N-H?O hydrogen bonds link the cations and anions into
      chains running parallel to the b axis. There is pi-pi stacking between symmetry
      related benzene rings with a centroid-centroid distance of 3.949 (3) A. The
      crystal studied was a non-merohedral twin, with a 19% minor component.

PMID- 22589887
TI  - 3,6,8-Tribromo-7-ethyl-amino-4-methyl-2H-chromen-2-one.
AB  - In the title mol-ecule, C(12)H(10)Br(3)NO(2), the 2H-chromen ring is essentially
      planar (r.m.s. deviation = 0.022 A) with the ethyl-amino group oriented at 13.9
      (5) degrees  with respect to the ring. The mol-ecular structure is stabilized by
      intra-molecular N-H?Br and C-H?Br interactions.

PMID- 22589888
TI  - 4,7,8-Trimethyl-2H-chromen-2-one.
AB  - The mol-ecule of the title compound, C(12)H(12)O(2), is essentially planar, with
      a maximum deviation from the mean plane of all non-H atoms of 0.038 (1) A for the
      methyl C atom in the 8-position. The crystal structure is characterized by anti
      parallel pi-pi stacking along the c axis, with centroid-centroid distances as
      short as 3.866 (1) A. In the crystal, C-H?O hydrogen bonds connect the mol-ecules
      across the stacks into ribbons in the a-axis direction.

PMID- 22589889
TI  - (2E)-2-[(2H-1,3-Benzodioxol-5-yl)methyl-idene]-2,3-dihydro-1H-inden-1-one.
AB  - In the title compound, C(17)H(12)O(3), each of the five-membered rings in the
      inden-1-one and 1,3-benzodioxole residues is almost planar (r.m.s. deviations =
      0.041 and 0.033 A, respectively). A small twist about the single bond linking the
      two residues is evident [the C-C-C-C torsion angle = 8.7 (4) degrees ]. Supra
      molecular zigzag layers propagating in the ac plane are formed in the crystal via
      C-H?O inter-actions. The layers are linked via pi-pi inter-actions between the
      five- and six-membered rings of 1,3-benzodioxole residues [centroid-centroid
      distance = 3.4977 (14) A].

PMID- 22589890
TI  - 1,3-Diphenyl-4,5-dihydro-1H-pyrazol-5-one.
AB  - In the title pyrazolone derivative, C(15)H(12)N(2)O, the five-membered ring is
      approximately planar (r.m.s. deviation = 0.018 A), and the N- and C-bound benzene
      rings are inclined to this plane [dihedral angles = 21.45 (10) and 6.96 (10)
      degrees , respectively] and form a dihedral angle of 20.42 (10) degrees  with
      each other. Supra-molecular layers are formed in the crystal structure via C-H?O
      and C-H?N inter-actions, and these are assembled into double layers by C-H?pi and
      pi-pi inter-actions between the pyrazole and C-bound benzene rings [ring centroid
      centroid distance = 3.6476 (12) A]. The double layers stack along the a axis
      being connected by pi-pi inter-actions between the N- and C-bound benzene rings
      [ring centroid-centroid distance = 3.7718 (12) A].

PMID- 22589891
TI  - 3,5-Dimethyl-1-(4-nitro-phen-yl)-1H-pyrazole.
AB  - In the title pyrazole derivative, C(11)H(11)N(3)O(2), the benzene ring is twisted
      [dihedral angle = 31.38 (12) degrees ] with respect to the pyrazole ring (r.m.s.
      deviation = 0.009 A). The nitro group is effectively coplanar with the benzene
      ring to which it is attached [O-N-C-C torsion angle = -6.5 (3) degrees ]. Supra
      molecular chains along the b axis are formed owing to pi-pi inter-actions [3.8653
      (2) A] between translationally related mol-ecules involving both the five- and
      six-membered rings.

PMID- 22589892
TI  - 6-Bromo-1H-indole-3-carb-oxy-lic acid.
AB  - In the title mol-ecule, C(9)H(6)BrNO(2), the dihedral angle between the -COOH
      group and the ring system is 6 (4) degrees . In the crystal, pairs of O-H?O
      hydrogen bonds link the mol-ecules into inversion dimers and these dimers are
      connected via N-H?O hydrogen bonds to form layers parallel to the (-101) plane.

PMID- 22589893
TI  - (6Z)-4-Bromo-6-{[(2-hy-droxy-eth-yl)amino]-methyl-idene}cyclo-hexa-2,4-dien-1
      one.
AB  - The title mol-ecule, C(9)H(10)BrNO(2), excluding methyl-ene H atoms and the C-OH
      group, is essentially planar, with a maximum deviation of 0.037 (2) A for the N
      atom. The N-C-C-O torsion angle is -63.1 (3) degrees . The mol-ecular structure
      is stabilized by a weak intra-molecular N-H?O(carbonyl) hydrogen bond, forming an
      S(6) motif. In the crystal, mol-ecules are linked by O-H?O and C-H?O hydrogen
      bonds, forming a three-dimensional network.

PMID- 22589894
TI  - 2-Phenyl-1H-imidazol-3-ium hydrogen fumarate-fumaric acid (2/1).
AB  - The asymmetric unit of the title compound, C(9)H(9)N(2) (+).C(4)H(3)O(4) (
      ).0.5C(4)H(4)O(4), consists of one 2-phenyl-imidazolium cation, one hydrogen
      fumarate anion and half a fumaric acid mol-ecule, which lies on an inversion
      center. N-H?O and O-H?O hydrogen bonds connect the cations, anions and fumaric
      acid mol-ecules into sheets parallel to the (102) plane.

PMID- 22589895
TI  - 1,4-Dihex-yloxy-2,5-bis-(2-nitro-phen-yl)benzene.
AB  - The title compound, C(30)H(36)N(2)O(6), was prepared via twofold Suzuki coupling
      of a diboronic acid with bromo-nitro-benzene. The mol-ecule is located on a
      crystallographic inversion centre. The lateral benzene ring and the central ring
      make a dihedral angle of 48.75 (14) degrees  and the nitro group is twisted by
      41.47 (13) degrees  out of the plane of the benzene ring. The nitro and hex-yloxy
      groups are in close proximity and the hex-yloxy chain adopts an all-anti
      conformation.

PMID- 22589896
TI  - 1-[3-(4-Chloro-phen-yl)-5-(4-meth-oxy-phen-yl)-4,5-dihydro-1H-pyrazol-1
      yl]ethanone.
AB  - In the title compound, C(18)H(17)ClN(2)O(2), the benzene rings form dihedral
      angles of 6.69 (6) and 74.88 (5) degrees  with the 4,5-dihydro-1H-pyrazole ring.
      The benzene rings form a dihedral angle of 76.67 (5) degrees  with each other. In
      the crystal, mol-ecules are linked via bifurcated (C,C)-H?O hydrogen bonds into
      chains along [010]. The crystal structure is further consolidated by C-H?pi inter
      actions.

PMID- 22589897
TI  - 2-[(E)-(Naphthalen-2-yl-imino)-meth-yl]-4-(trifluoro-meth-oxy)phenol.
AB  - In the title compound, C(18)H(12)F(3)NO(2), the planes of the benzene ring and
      the naphthalene system form a dihedral angle of 47.21 (3) degrees . The hy-droxy
      group is involved in an intra-molecular O-H?N hydrogen bond. In the crystal, weak
      C-H?O and C-H?F inter-actions link the mol-ecules related by translations along
      the c and a axes, respectively, into sheets.

PMID- 22589898
TI  - Dimethyl dl-2,3-dibenzyl-2,3-diisothio-cyanatosuccinate.
AB  - The title compound, C(22)H(20)N(2)O(4)S(2), has approximate mol-ecular twofold
      symmetry. In the crystal, the presence of C-H?pi inter-actions leads to the
      formation of zigzag chains along [001].

PMID- 22589899
TI  - N,N'-Bis[(E)-1-(thio-phen-3-yl)ethyl-idene]ethane-1,2-diamine.
AB  - The complete mol-ecule of the title compound, C(14)H(16)N(2)S(2), is generated by
      a crystallographic inversion centre. The thio-phene residue is close to being
      coplanar with the imine group [C-C-C-N torsion angle = 6.5 (2) degrees ], and the
      conformation about the imine C=N bond [1.281 (2) A] is E. In the crystal, the
      three-dimensional architecture is consolidated by C-H?N, C-H?pi and S?S [3.3932
      (7) A] inter-actions.

PMID- 22589900
TI  - 3-Amino-1-(thio-phen-2-yl)-9,10-dihydro-phenanthrene-2,4-dicarbonitrile.
AB  - In the title compound, C(20)H(13)N(3)S, the partially saturated ring adopts a
      twisted half-boat conformation with the methyl-ene C atom closest to the amino
      benzene ring lying 0.690 (6) A out of the plane defined by the five remaining
      atoms. The dihydro-phenanthrene residue has a folded conformation [dihedral angle
      between the outer benzene rings = 26.27 (18) degrees ]. The thio-phen-2-yl ring
      forms a dihedral angle of 63.76 (19) degrees  with the benzene ring to which it
      is attached. In the crystal, inversion dimers linked by pairs of N-H?N hydrogen
      bonds generate R(2) (2)(12) loops. The dimers are linked into layers in the bc
      plane by weak C-H?pi inter-actions. The thio-phen-2-yl ring is disordered over
      two essentially coplanar but opposite orientations in a 0.918 (4):0.082 (4)
      ratio.

PMID- 22589901
TI  - N-(4-Chloro-butano-yl)-N'-[2-(trifluoro-meth-yl)phen-yl]thio-urea.
AB  - In the title compound, C(12)H(12)ClF(3)N(2)OS, the dihedral angle between the
      benzene ring and the thio-urea fragment is 69.41 (5) degrees . The thio-urea N-H
      atoms adopt an anti conformation, such that one of them forms an intra-molecular
      N-H?O hydrogen bond, generating an S(6) ring. In the crystal, both N-H groups
      form inversion dimers, one via a pair of N-H?S hydrogen bonds and one via a pair
      of N-H?O hydrogen bonds. These lead to R(2) (2)(8) and R(2) (2)(12) loops,
      respectively. Weak C-H?Cl, C-H?F, C-H?S and pi-pi [centroid-centroid separation =
      3.7098 (6)A and slippage = 1.853 A] inter-actions also occur.

PMID- 22589902
TI  - (E)-4-Amino-N-(1,2-dihydro-pyridin-2-yl-idene)benzene-sulfonamide nitro-methane
      monosolvate.
AB  - In the title solvate, C(11)H(11)N(3)O(2)S.CH(3)NO(2), the dihedral angle between
      the benzene ring and the N-containing ring is 85.94 (11) degrees , and an
      approximate V shape arises for the sulfonamide mol-ecule. In the crystal, N-H?O
      and N-H?N hydrogen bonds and weak C-H?O inter-actions link the sulfonamide mol
      ecules into a three-dimensional network. The nitro-methane solvent mol-ecules are
      located in the inter-stitial sites in the sulfonamide network.

PMID- 22589903
TI  - 6-(3,5-Dimethyl-benz-yl)-5-ethyl-1-[(2-phenyl-eth-oxy)meth-yl]pyrimidine
      2,4(1H,3H)dione.
AB  - In the title pyrimidine derivative, C(24)H(28)N(2)O(3), the uracil unit is
      essentially planar with an r.m.s. deviation of 0.0054 (1) A for the eight non-H
      atoms. The pyrimidine ring is tilted by a dihedral angle of 77.08 (7) degrees 
      with respect to the aromatic ring of the 3,5-dimethyl-benzyl substituent, whereas
      it is nearly parallel to the benzene ring of the pheneth-oxy-methyl unit, with a
      dihedral angle of 8.17 (8) degrees . An intra-molecular C-H?O hydrogen bond
      generates an S(6) ring motif. In the crystal, mol-ecules are linked by a pair of
      amide-uracil N-H?O hydrogen bonds into an inversion R(2) (2)(8) dimer. These
      dimers are stacked along the b axis through pi-pi inter-actions with a centroid
      centroid distance of 3.9517 (8) A. Weak C-H?pi inter-actions are also present.

PMID- 22589904
TI  - 1-(4-Methyl-phen-yl)-2-(phenyl-sulfon-yl)ethanone.
AB  - In the title compound, C(15)H(14)O(3)S, the benzene and phenyl rings make a
      dihedral angle of 33.56 (16) degrees . In the crystal, mol-ecules are linked by C
      H?O hydrogen bonds into a layer parallel to the ab plane.

PMID- 22589905
TI  - Ethyl 2-(7-oxo-3,5-diphenyl-1,4-diaze-pan-2-yl)acetate.
AB  - In the title compound, C(21)H(24)N(2)O(3), the diazepane ring adopts a chair
      conformation. The central diazepane ring forms dihedral angles 67.80 (7) and
      72.29 (5) degrees  with the two benzene rings. The eth-oxy-carbonyl group is
      disordered over two conformations with site-occupancy factors of 0.643 (5) and
      0.357 (5). In the crystal, inversion dimers linked by pairs of N-H?O hydrogen
      bonds generate R(2) (2)(8) loops.

PMID- 22589906
TI  - (E)-3-[(3-Eth-oxy-2-hy-droxy-benzyl-idene)amino]-benzoic acid.
AB  - In the title compound, C(16)H(15)NO(4), a potential bidentate N,O-donor Schiff
      base ligand, the benzene rings are inclined to one another by 4.24 (12) degrees .
      The mol-ecule has an E conformation about the C=N bond. An intra-molecular O-H?N
      hydrogen bond makes an S(6) ring motif. In the crystal, pairs of O-H?O hydrogen
      bonds link the mol-ecules, forming inversion dimers with R(2) (2)(8) ring motifs.
      These dimers are further connected by C-H?O inter-actions, forming a sheet in
      (104). There is also a C-H?pi inter-action present involving neighbouring mol
      ecules.

PMID- 22589907
TI  - (E)-4-[(4-Diethyl-amino-2-hy-droxy-benzyl-idene)amino]-benzoic acid.
AB  - In the title compound, C(18)H(20)N(2)O(3), a potential bidentate N,O-donor Schiff
      base ligand, the benzene rings are inclined at an angle of 12.25 (19) degrees .
      The mol-ecule has an E conformation about the C=N bond. One of the ethyl groups
      is disordered over two positions, with a refined site-occupancy ratio of 0.55
      (1):0.45 (1). An intra-molecular O-H?N hydrogen bond makes an S(6) ring motif. In
      the crystal, pairs of O-H?O hydrogen bonds link mol-ecules, forming inversion
      dimers with R(2) (2)(8) ring motifs.

PMID- 22589908
TI  - Triprolidinium dichloranilate-chloranilic acid-methanol-water (2/1/2/2).
AB  - In the triprolidinium cation of the title compound {systematic name: 2-[1-(4
      methyl-phen-yl)-3-(pyrrolidin-1-ium-1-yl)prop-1-en-1-yl]pyridin-1-ium bis-(2,5
      dichloro-4-hy-droxy-3,6-dioxo-cyclo-hexa-1,4-dien-1-olate)-2,5-dichloro-3,6-dihy
      droxy-cyclo-hexa-2,5-diene-1,4-dione-methanol-water (2/1/2/2)}, C(19)H(24)N(2)
      (2+).2C(6)HCl(2)O(4) (-).0.5C(6)H(2)Cl(2)O(4).CH(3)OH.H(2)O, the N atoms on both
      the pyrrolidine and pyridine groups are protonated. The neutral chloranilic acid
      mol-ecule is on an inversion symmetry element and its hy-droxy H atoms are
      disordered over two positions with site-occupancy factors of 0.53 (6) and 0.47
      (6). The methanol solvent mol-ecule is disordered over two positions in a 0.836
      (4):0.164 (4) ratio. In the crystal, N-H?O, O-H?O and C-H?O inter-actions link
      the components. The crystal structure also features pi-pi inter-actions between
      the benzene rings [centroid-centroid distances = 3.5674 (15), 3.5225 (15) and
      3.6347 (15) A].

PMID- 22589909
TI  - (E)-4-[(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)imino-meth-yl]-2
      meth-oxy-phenyl 4-bromo-benzene-sulfonate.
AB  - In the title compound, C(25)H(22)BrN(3)O(5)S, the central benzene ring makes
      dihedral angles of 4.41 (10), 67.09 (9) and 62.05 (10) degrees , respectively,
      with the pyrazolone, bromo-benzene and terminal phenyl rings. The dihedral angle
      between the pyrazolone and phenyl rings is 57.75 (11) degrees . In the crystal,
      two pairs of C-H?O hydrogen bonds link the mol-ecules into inversion dimers. A
      weak intra-molecular C-H?O hydrogen bonds is also observed.

PMID- 22589910
TI  - 4,6-Bis(diphenyl-phosphan-yl)-2,8-di-methyl-phenoxathiin dichloro-methane
      monosolvate.
AB  - The title compound, C(38)H(30)OP(2)S.CH(2)Cl(2), belongs to the xanthene family
      of ligands containing S- and O-donor atoms in the central heterocylic ring.
      Positions 2 and 8 on the xanthene backbone are functionalized with methyl groups
      to allow for the selective functionalization of the backbone at positions 4 and 6
      with diphenyl-phosphanyl units. The title compound shows a significant 'roof
      like' bending along the axis of planarity involving the O- and S-donor atoms and
      the benzene rings, resulting in a dihedral angle between the mean planes of the
      benzene rings of 32.88 (13) degrees .

PMID- 22589911
TI  - rac-18-Meth-oxy-coronaridine hydro-chloride.
AB  - In the crystal structure of the racemic title compound, C(22)H(29)N(2)O(3)
      (+).Cl(-), both NH groups form N-H?Cl hydrogen bonds with the chloride counter
      ion, forming translational chains along the a axis.

PMID- 22589912
TI  - N'-(3,5-Dichloro-2-hy-droxy-benzyl-idene)-4-(dimethyl-amino)-benzohydrazide
      methanol monosolvate.
AB  - The title compound, C(16)H(15)Cl(2)N(3)O(2).CH(3)OH, a Schiff base molecule, is
      prepared by the reaction of 3,5-dichloro-salicyl-aldehyde with 4-dimethyl-amino
      benzohydrazide in methanol. The Schiff base mol-ecule is approximately planar,
      with a mean deviation from the least-squares plane defined by the non-H atoms of
      0.0452 (3) A, and with a dihedral angle between the benzene rings of 4.2 (3)
      degrees . This planarity is assisted by the formation of an intra-molecular O-H?N
      hydrogen bond. In the crystal, adjacent Schiff base mol-ecules are linked by two
      methanol mol-ecules through N-H?O and O-H?O hydrogen bonds, forming dimers.

PMID- 22589913
TI  - 3-Chloro-4-methyl-quinolin-2(1H)-one.
AB  - The title compound, C(10)H(8)ClNO, is almost planar (r.m.s. deviation for the 13
      non-H atoms = 0.023 A). In the crystal, inversion dimers linked by pairs of N-H?O
      hydrogen bonds generate R(2) (2)(8) rings. Weak aromatic pi-pi stacking inter
      actions [centroid-centroid distance = 3.7622 (12) A] also occur.

PMID- 22589914
TI  - 2-Methyl-pyridinium 5-(2,4-dinitro-phen-yl)-1,3-dimethyl-barbiturate.
AB  - In the title mol-ecular salt [systematic name: 2-methyl-pyridinium 5-(2,4-dinitro
      phen-yl)-1,3-dimethyl-2,6-dioxo-1,2,3,6-tetra-hydro-pyrimidin-4-olate],
      C(6)H(8)N(+).C(12)H(9)N(4)O(7) (-), the cation and anion are linked a through
      strong N-H?O hydrogen bond. In the crystal, C-H?O inter-actions link the ions,
      generating a chain along [010].

PMID- 22589915
TI  - Diphenyl[2-(phenyl-sulfon-yl)propan-2-yl]-lambda(5)-phosphane-thione.
AB  - The title compound, C(21)H(21)O(2)PS(2), was obtained from the corresponding
      dilithio methandiide by treatment with iodo-methane. The bond lengths and angles
      deviate considerably from those in the dimetallated compound. These differences
      are most pronounced in the PCS backbone. While the title compound features C-P
      and C-S distances of 1.9082 (17) and 1.8348 (17) A, respectively, the dianion
      showed C-P(av) distances shortened by 11% [1.710 (4) A] and C-S distances
      shortened by 12% [1.614 (3) A]. Additionally, the P-C-S angle experiences a
      contraction by methyl-ation of the dianion from 121.4 (2) to 111.96 (9) degrees 
      in the title compound.

PMID- 22589916
TI  - 5-(4-Methyl-phenyl-sulfon-yl)-1,3-dithiolo[4,5-c]pyrrole-2-thione.
AB  - The asymmetric unit of the title compound, C(12)H(9)NO(2)S(4), contains one half
      mol-ecule with the N, two S amd four C atoms lying on a mirror plane. The mol
      ecule exhibits a V-shaped conformation, with a dihedral angle of 87.00 (7)
      degrees  between the benzene and dithiol-opyrrole rings. The methyl group was
      treated as rotationally disordered between two orientations in a 1:1 ratio. In
      the crystal, weak C-H?O hydrogen bonds link the mol-ecules into chains in [010].

PMID- 22589917
TI  - 1-(4-tert-Butyl-benz-yl)pyrimidine-2,4(1H,3H)-dione.
AB  - The asymmetric unit of the title compound, C(15)H(18)N(2)O(2), contains two
      independent mol-ecules with essentially identical geometries and conformations.
      The dihedral angles between the benzene and pyrimidine rings in the two mol
      ecules are 89.96 (11) and 73.91 (11) degrees . The six methyl groups are
      disordered over two sets of sites, with site occupancies of 0.545 (4):0.455 (4)
      and 0.542 (7):0.458 (7) in the two mol-ecules. The crystal structure is
      stabilized by N-H?O hydrogen bonds.

PMID- 22589918
TI  - 1-(4-Chloro-2-fluoro-phen-yl)-4-difluoro-methyl-3-methyl-1H-1,2,4-triazol-5(4H)
      one.
AB  - In the crystal structure of the title compound, C(10)H(7)ClF(3)N(3)O, pairs of
      mol-ecules are connected into dimers via pairs of C-H?O hydrogen bonds. The
      dihedral angle between the benzene ring and attached triazolone ring is 53.2 (1)
      degrees .

PMID- 22589919
TI  - 1-(3,3-Dichloro-all-yloxy)-2-nitro-benzene.
AB  - In the title compound, C(9)H(7)Cl(2)NO(3), the dihedral angle between the benzene
      ring and the plane of the nitro group is 50.2 (1) degrees , and that between the
      benzene ring and the best plane through the dichloro-allyl fragment is 40.1 (1)
      degrees .

PMID- 22589920
TI  - 4a-Methyl-2,3,4,4a-tetra-hydro-1H-carbazole-6-sulfonamide.
AB  - In the title mol-ecule, C(13)H(16)N(2)O(2)S, the nine non-H atoms comprising the
      indole residue are approximately coplanar (r.m.s. deviation = 0.031 A). The
      partially saturated ring adopts a chair conformation. One amine H forms an inter
      molecular N-H?O hydrogen bond to a sulfonamide O atom, while the other amine H
      form is connected to the indole N atom of an adjacent mol-ecule via an N-H?N
      hydrogen bond, resulting in a three-dimensional architecture.

PMID- 22589921
TI  - 3,5-Dimethyl-1-phenyl-1H-pyrazole-4-carbaldehyde.
AB  - In the title mol-ecule, C(12)H(12)N(2)O, the five- and six-membered rings form a
      dihedral angle of 68.41 (16) degrees . The aldehyde group is nearly coplanar with
      the pyrazole ring [C-C-C-O torsion angle = -0.4 (5) degrees ]. The three
      dimensional architecture is sustained by weak C-H?O and C-H?pi inter-actions.

PMID- 22589922
TI  - 1,1'-Bis(3-methyl-3-phenyl-cyclo-but-yl)-2,2'-(aza-nedi-yl)diethanol.
AB  - The title mol-ecule, C(26)H(35)NO(2), contains two cyclo-butane rings that adopt
      butterfly conformations and are linked by a -CH(OH)CH(2)NHCH(2)CH(OH)- bridge. In
      the crystal, N-H?O, O-H?N and O-H?O hydrogen bonds together with C-H?pi inter
      actions link the molecules.

PMID- 22589923
TI  - 5-(2-Chloro-benz-yl)-4,5,6,7-tetra-hydro-thieno[3,2-c]pyridin-2-yl acetate.
AB  - In the title compound, C(16)H(16)ClNO(2)S, the benzene and thio-phene rings make
      a dihedral angle of 72.60 (4) degrees . In the crystal, weak C-H?O inter-actions
      are observed.

PMID- 22589924
TI  - (R)-Doxylaminium (R,R)-tartrate.
AB  - IN THE TITLE COMPOUND (SYSTEMATIC NAME: (R)-dimeth-yl{2-[1-phenyl-1-(pyridin-2
      yl)eth-oxy]eth-yl}aza-nium (R,R)-3-carb-oxy-2,3-dihy-droxy-propano-ate),
      C(17)H(23)N(2)O(+).C(4)H(5)O(6) (-), the doxylaminium cation is protonated at the
      N atom. The tartrate monoanions are linked by short, almost linear O-H?O hydrogen
      bonds into chains extended along [100]. These chains are inter-linked by anion
      pyridine O-H?N hydrogen bonds into a two-dimensional grid structure. WeakC-H?O
      inter-actions also play a role in the crystal packing. An intra-molecular hy
      droxy-carboxyl-ate O-H?O hydrogen bond influences the conformation of the anion:
      the hydrogen-bonded fragment is almost planar, the maximum deviation from the
      mean plane being 0.059 (14) A. In the cation, the aromatic rings are almost
      perpendicular [dihedral angle = 84.94 (8) degrees ] and the conformation of the O
      C-C-N chain is gauche(-), the dihedral angle is -76.6 (2) degrees . The absolute
      configuration was assigned on the basis of known chirality of the parent
      compound.

PMID- 22589925
TI  - 3beta-Chloro-6-[2-(2-cyano-acet-yl)hydrazin-1-yl-idene]-5alpha-cholestane.
AB  - The asymmetric unit of the title compound, C(30)H(48)ClN(3)O, contains two mol
      ecules, A and B. In both mol-ecules, the three cyclo-hexane rings in the steroid
      fused ring systems adopt chair conformations, while the cyclo-pentane rings adopt
      envelope and twist conformations in mol-ecules A and B, respectively. In mol
      ecule B, the cyano group is disordered over two orientations with refined site
      occupancies of 0.593 (8) and 0.407 (8). An intra-molecular C-H?N inter-action
      forms an S(10) ring in both mol-ecules. In the crystal, mol-ecules are linked by
      N-H?O, C-H?O and C-H?N inter-actions, resulting is chains propagating along the a
      axis direction.

PMID- 22589926
TI  - 1-(4-Chloro-phen-yl)-2-[4-hy-droxy-3-(3-meth-oxy-benzo-yl)-1,1-dioxo-2H
      1lambda(6),2-benzothia-zin-2-yl]ethanone.
AB  - In the title mol-ecule, C(24)H(18)ClNO(6)S, the heterocyclic thia-zine ring
      adopts a half-chair conformation with the S and N atoms displaced by 0.406 (5)
      and 0.444 (5) A, respectively, on opposite sides of the mean plane formed by the
      remaining ring atoms. The meth-oxy-benzoyl and the chloro-phenyl rings lie
      roughly parallel to each other, with a dihedral angle between the mean planes of
      these rings of 8.86 (10) degrees . The mol-ecular structure is consolidated by
      intra-molecular O-H?O and C-H?O inter-actions and the crystal packing is
      stabilized by inter-molecular O-H?O and C-H?Cl hydrogen bonds.

PMID- 22589927
TI  - 9-(4-Hy-droxy-3,5-dimeth-oxy-phen-yl)-3,3,6,6-tetra-methyl-3,4,5,6,7,9-hexa-hydro
      1H-xanthene-1,8(2H)-dione.
AB  - In the title compound, C(25)H(30)O(6), the two fused cyclo-hexa-none rings have
      envelope conformations, whereas the central pyran ring is roughly planar [mximum
      deviation = 0.045 (2) A]. The pyran and benzene rings are almost perpendicular to
      each other, making a dihedral angle of 86.32 (2) degrees . In the crystal,
      molecules are linked via pairs of O-H?O hydrogen bonds, forming inversion dimers.

PMID- 22589929
TI  - Methyl 2-{[(3-methyl-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-4-yl-idene)(4-nitro
      phen-yl)meth-yl]amino}-3-phenyl-propano-ate.
AB  - The mol-ecule of the title compound, C(27)H(24)N(4)O(5), exists in the keto
      enamine tautomeric form, stabilized by an intra-molecular N-H?O hydrogen bond. An
      intra-molecular C-H?.O hydrogen bond also occurs. In the crystal, C-H?O hydrogen
      bonds link the mol-ecules into chains.

PMID- 22589928
TI  - 6H,13H-5,12:7,14-Dimethano-dinaphtho-[2,3-d:2,3-i][1,3,6,8]tetra-azecine.
AB  - In the title compound, C(24)H(20)N(4), obtained through the condensation of
      naphthalene-2,3-diamine with formaldehyde in methanol, the mol-ecule is located
      on a special position of site symmetry -4. Due to symmetry considerations, the
      aromatic rings are strictly perpendicular to each other. In the crystal, mol
      ecules are linked by pairs of C-H?pi inter-actions into columns along [110].

PMID- 22589930
TI  - 3-(4-Chloro-anilino)-5,5-dimethyl-cyclo-hex-2-en-1-one.
AB  - The asymmetric unit of the title compound, C(14)H(16)ClNO, contains two
      independent mol-ecules, both with the cyclo-hexene ring in a sofa conformation.
      In the crystal, N-H?O hydrogen bonds link the mol-ecules related by translation
      along the a axis into two crystallographically independent chains. Weak C-H?pi
      inter-actions are also observed.

PMID- 22589931
TI  - 3,3'-Dihy-droxy-6,6'-bis-(hy-droxy-meth-yl)-2,2'-(pentane-1,1-di-yl)di-4H-pyran-4
      one.
AB  - In the title mol-ecule, C(17)H(20)O(8), the two pyran rings form a dihedral angle
      of 61.2 (2) degrees . The two hy-droxy-methyl groups are each disordered over two
      sets of sites in a 0.764 (3):0.236 (3) ratio. In the crystal, O-H?O hydrogen
      bonds link the mol-ecules into layers parallel to the ac plane.

PMID- 22589932
TI  - (2E)-2-(Furan-2-yl-methyl-idene)-2,3-dihydro-1H-inden-1-one.
AB  - In the title compound, C(14)H(10)O(2), the five-membered ring of the inden-1-one
      residue is almost planar (r.m.s. deviation = 0.035 A). A twist about the single
      bond linking the two residues is evident [C-C-C-C torsion angle = -13.2 (5)
      degrees ]. The three-dimensional architecture is stabilized by C-H?O (involving
      the trifurcated carbonyl O atom), C-H?pi and pi-pi inter-actions [between the
      five- and six-membered rings of inden-1-one residues; ring centroid-centroid
      distance = 3.7983 (17) A]. The sample studied was a non-merohedral twin; the
      minor component refined to approximately 36%.

PMID- 22589933
TI  - (1H-1,2,3-Benzotriazol-1-yl)methyl 2,2-dimethyl-propano-ate.
AB  - In the title compound, C(12)H(15)N(3)O(2), the dihedral angle between the mean
      planes of the benzene and triazole rings is 0.331 (53)  degrees . The side chain
      of the pivalate unit forms a dihedral angle of 69.04 (12) degrees  with the
      benzotriazole unit. The ester group and two methyl groups of the pivalate unit
      are disordered with an occupancy ratio of 0.731 (3):0.269 (3). In the crystal,
      weak pi-pi stacking inter-actions are observed between inversion-related benzene
      rings [centroid-centroid distance = 3.9040 (1) A].

PMID- 22589935
TI  - 5-Cyclo-hexyl-2-methyl-3-(4-methyl-phenyl-sulfon-yl)-1-benzofuran.
AB  - In the title compound, C(22)H(24)O(3)S, the cyclo-hexyl ring adopts a chair
      conformation. The 4-methyl-phenyl ring makes a dihedral angle of 80.95 (4)
      degrees  with the mean plane [mean deviation = 0.011 (1) A] of the benzofuran
      fragment. In the crystal, mol-ecules are linked by weak C-H?O and C-H?pi inter
      actions.

PMID- 22589934
TI  - (E)-3-[(2-Hy-droxy-3-meth-oxy-benzyl-idene)amino]-benzoic acid.
AB  - In the title compound, C(15)H(13)NO(4), the dihedral angle between the
      substituted benzene rings is 9.9 (8) degrees . Part of the mol-ecule (the
      salicylaldimine segment) is disordered over two sets of sites, with a refined
      site-occupancy ratio of 0.550 (14):0.450 (14). Intra-molecular O-H?N hydrogen
      bonds form S(6) ring motifs. In the crystal, pairs of O-H?O hydrogen bonds link
      mol-ecules into centrosymmetric dimers with R(2) (2)(8) ring motifs. The crystal
      packing also features C-H?pi inter-actions.

PMID- 22589936
TI  - (E)-4-Bromo-N'-(4-hy-droxy-3-meth-oxy-benzyl-idene)benzohydrazide monohydrate.
AB  - In the title compound, C(15)H(13)BrN(2)O(3).H(2)O, the dihedral angle between the
      two benzene rings is 13.92 (6) degrees . The meth-oxy group of the 4-hy-droxy-3
      meth-oxy-phenyl is almost coplanar with its bound benzene ring, as seen by the
      C(meth-yl)-O-C-C torsion angle of -0.35 (16) degrees . In the crystal, mol-ecules
      are linked into a three-dimensional network by N-H?O, O-H?N and O-H?O hydrogen
      bonds and also weak C-H?O inter-actions. A short C?O contact of 3.0191 (15) A is
      also present.

PMID- 22589937
TI  - 4-Fluoro-2-[(3-methyl-phen-yl)imino-meth-yl]phenol.
AB  - The title compound, C(14)H(12)FNO, crystallizes as the trans phenol-imine
      tautomer. The two benzene rings are essentially coplanar, being inclined to one
      another by 9.28 (7) degrees . This is at least in part due to the intra-molecular
      O-H?N hydrogen bond between the hy-droxy O atom and the imine N atom. The crystal
      structure is stabilized by an array of weak C-H?O and C-H?F inter-actions, which
      link the mol-ecules into a stable three-dimensional network.

PMID- 22589938
TI  - 8-O-Acetyl-8-epi-9-de-oxygoniopypyrone.
AB  - THE TITLE COMPOUND (SYSTEMATIC NAME: 7-oxo-3-phenyl-2,6-dioxabicyclo-[3.3.1]nonan
      4-yl acetate), C(15)H(16)O(5), is a styryllactone derivative which was isolated
      from Goniothalamus macrophyllus. The mol-ecule has two fused rings consisting of
      a tetra-hydro-2H-pyran and a lactone ring, with the benzene ring and the acetyl
      group attached to the tetra-hydro-2H-pyran ring. The tetra-hydro-2H-pyran ring is
      in a standard chair conformation, whereas the lactone ring is in an envelope
      conformation. In the crystal, mol-ecules are linked by weak C-H?O inter-actions
      into sheets parallel to the ac plane. Weak C-H?pi inter-actions are also
      observed.

PMID- 22589940
TI  - 2-Trifluoro-methyl-1H-benzimidazol-3-ium tetra-fluoro-borate-2-trifluoro-methyl
      1H-benzimidazole-water (1/1/1).
AB  - The asymmetric unit of the title compound, C(8)H(6)F(3)N(2) (+).BF(4) (
      ).C(8)H(5)F(3)N(2).H(2)O, consists of two 2-trifluoro-methyl-benzimidazole mol
      ecules, each of which is protonated on a 50% basis, one tetra-fluoro-borate anion
      and a water mol-ecule. The two 2-trifluoromethylbenzimidazole mol-ecules thus
      exist as half-neutral half-cation entities. They are linked by N-H?N hydrogen
      bonds involving the half-occupancy hydrogens in each mol-ecule. The F atoms of
      one of the trifluoro-methyl groups are disordered over two sets of sites [in a
      0.518 (14):0.482 (14) ratio], as are the F atoms of the tetra-fluoroborate anion
      [0.507 (14):0.493 (14) ratio]. The water mol-ecule is linked to one of the 2
      trifluoro-methyl-benzimidazole mol-ecules via an N-H?O hydrogen bond.

PMID- 22589939
TI  - S-Phenyl 4-meth-oxy-benzothio-ate.
AB  - In the mol-ecule of the title thio-ester, C(14)H(12)O(2)S, the dihedral angle
      between the phenyl and benzene rings is 71.8 (3) degrees . The meth-oxy group is
      essentially coplanar with the benezene ring to which it is bonded, with an r.m.s.
      deviation of 0.0065 (5) A for the non-H atoms involved. In the crystal, weak C
      H?pi inter-actions are present.

PMID- 22589941
TI  - 1-[Bis(4-fluoro-phen-yl)meth-yl]-4-[2-(2-methyl-phen-oxy)eth-yl]piperazine.
AB  - In the title mol-ecule, C(26)H(28)F(2)N(2)O, the piperazine ring adopts a chair
      conformation, with the N-bonded substituents in equatorial orientations. The
      dihedral angle between the fluoro-benzene rings is 69.10 (15).

PMID- 22589942
TI  - N'-(4-Diethyl-amino-2-hy-droxy-benzyl-idene)-4-methyl-benzohydrazide.
AB  - The title compound, C(19)H(23)N(3)O(2), was prepared by condensing 4-diethyl
      amino-2-hy-droxy-benzaldehyde and 4-methyl-benzo-hydrazide in methanol. The
      asymmetric unit contains two independent mol-ecules in which the two benzene
      rings make dihedral angles of 30.3 (3) and 18.9 (3) degrees . Intra-molecular O
      H?N hydrogen bonds are observed in both mol-ecules. The crystal structure is
      stabilized by N-H?O hydrogen bonds, which form chains along the a axis.

PMID- 22589943
TI  - N'-(5-Chloro-2-hy-droxy-benzyl-idene)-4-meth-oxy-benzohydrazide.
AB  - The asymmetric unit of the title compound, C(15)H(13)ClN(2)O(3), contains two
      independent hydrazone mol-ecules. Each mol-ecule adopts an E configuration with
      respect to the methyl-idene unit and forms an intra-molecular O-H?N hydrogen
      bond. The principal difference between the two unique mol-ecules is the relative
      orientation of the two benzene rings, the dihedral angles between them being 4.0
      (3) and 65.9 (3) degrees , respectively. In the crystal, mol-ecules are linked
      through N-H?O hydrogen bonds, forming chains running along the c axis.

PMID- 22589944
TI  - (E)-Benzaldehyde O-{[3-(pyridin-3-yl)isoxazol-5-yl]meth-yl}oxime.
AB  - The asymmetric unit of the title compound, C(16)H(13)N(3)O(2), contains two
      independent mol-ecules in which the pyridine and benzene rings form dihedral
      angles of 81.7 (2) and 79.8 (2) degrees , indicating the twist in the mol-ecules.
      In the crystal, weak C-H?N inter-actions link mol-ecules into chains along [100].

PMID- 22589946
TI  - 2,3,5,6-Tetra-fluoro-1,4-bis-(trimethyl-sil-yl)benzene.
AB  - The asymmetric unit of the title compound, C(12)H(18)F(4)Si(2), contains two
      independent mol-ecules, both lying on inversion centers. The C(arene)-Si
      distances are significantly longer than in the analogous non-fluorinated
      compound. The packing of the mol-ecules results in a herringbone motif in the ac
      plane.

PMID- 22589945
TI  - 2-[(1H-Imidazol-1-yl)meth-yl]-1-[4-(trifluoro-meth-yl)phen-yl]-1H-indole.
AB  - In the title compound, C(19)H(14)F(3)N(3), the dihedral angles between the mean
      planes of the indole ring and the 4-CF(3)-phenyl and imidazole rings are 54.95
      (4) and 61.36 (7) degrees , respectively.

PMID- 22589947
TI  - 1-{2-Hy-droxy-6-[3-(pyrrol-1-yl)prop-oxy]phen-yl}ethanone.
AB  - In the title compound, C(15)H(17)NO(3), the mean planes of the pyrrole and
      benzene rings form a dihedral angle of 81.92 (7) degrees . The mol-ecule contains
      an intra-molecular O-H?O hydrogen bond. In the crystal, weak C-H?pi inter-actions
      link the mol-ecules into chains along [010].

PMID- 22589948
TI  - (2Z)-2-{[N-(2-Formyl-phen-yl)-4-methyl-benzene-sulfonamido]-meth-yl}-3-(4-methyl
      phen-yl)prop-2-ene-nitrile.
AB  - In the title compound, C(25)H(22)N(2)O(3)S, the sulfonyl-bound benzene ring forms
      dihedral angles of 36.8 (2) and 81.4 (2) degrees , respectively, with the formyl
      benzene and methyl-benzene rings. The mol-ecular conformation is stabilized by an
      intra-molecular C-H?O hydrogen bond, which generates an S(5) ring motif. The
      crystal packing is stabilized by C-H?O hydrogen bonds, which generate C(11)
      chains along the b axis. The crystal packing is further stabilized by pi-pi inter
      actions [centroid-centroid distance = 3.927 (2) A].

PMID- 22589949
TI  - (2E)-1-(2,6-Dichloro-3-fluoro-phen-yl)-3-phenyl-prop-2-en-1-one.
AB  - In the title compound, C(15)H(9)Cl(2)FO, the F atom shows positional disorder
      over two positions, with site-occupancy factors of 0.747 (4) and 0.253 (4). The
      dihedral angle between the rings is 86.37 (10) degrees . In the crystal, C-H?O
      contacts connect the mol-ecules into chains along the c axis. The shortest inter
      centroid distance between two aromatic systems is 3.6686 (12) A and is apparent
      between the halogenated rings.

PMID- 22589950
TI  - 1-(4-Methyl-phen-yl)-3-phenyl-1H-pyrazol-5-yl 4-nitro-benzene-sulfonate.
AB  - In the title mol-ecule, C(22)H(17)N(3)O(5)S, the pyrazole ring is planar (r.m.s.
      deviation = 0.018 A) and forms dihedral angles of 21.45 (10) and 6.96 (10)
      degrees  with the N- and C-bound benzene rings, respectively. Supra-molecular
      layers in the bc plane are formed in the crystal via C-H?O and pi-pi inter
      actions involving the sulfonamide benzene ring inter-acting with the N- and C
      bound benzene rings [centroid-centroid distances = 3.790 (2) and 3.730 (2) A,
      respectively]. The crystal studied was found to be a merohedral twin (twin law 1
      0 0.678, 0 -1 0, 0 0 -1), the fractional contribution of the minor component
      being approximately 36%.

PMID- 22589951
TI  - 1-Phenyl-1H-pyrazole-4-carbaldehyde.
AB  - In the title mol-ecule, C(10)H(8)N(2)O, the five- and six-membered rings form a
      dihedral angle of 10.14 (9) degrees . The aldehyde group is almost coplanar with
      the pyrazole ring to which it is connected [O-C-C-C torsion angle = -179.35 (17)
      degrees ]. In the crystal, inversion dimers are linked by four C-H?O inter
      actions as the carbonyl O atom accepts two such bonds. The dimeric aggregates are
      linked into supra-molecular layers in the ac plane by C-H?pi and pi-pi [ring
      centroid(pyrrole)?ring centroid(phen-yl) = 3.8058 (10) A] inter-actions.

PMID- 22589952
TI  - 4-Allyl-morpholin-4-ium bromide.
AB  - The title compound, C(7)H(14)NO(+).Br(-), was formed by reaction of 4-allyl
      morpholine and hydrogen bromide. In the crystal, mol-ecules are connected via N
      H?Br and C-H?Br hydrogen bonds, forming a three-dimensional network.

PMID- 22589953
TI  - (E)-2-(2-Hy-droxy-5-iodo-benzyl-idene)hydrazinecarboxamide.
AB  - In the title mol-ecule, C(8)H(8)IN(3)O(2), there is an intra-molecular O-H?N
      hydrogen bond between the hy-droxy group and the imine N atom, which generates an
      S(6) ring. In the crystal, the carbonyl O atom accepts two different N-H?O
      hydrogen bonds, which connect mol-ecules with two R(2) (2)(8) motifs.

PMID- 22589954
TI  - rac-[3-Hydroxy-6,9-dimethyl-6-(4-methylpent-3-en-1-yl)-6a,7,8,9,10,10a-hexahydro
      6H-1,9-epoxybenzo[c]chromen-4-yl](phenyl)methanone.
AB  - The title compound congestiflorone, C(28)H(32)O(4), which was isolated from the
      stem bark of Mesua congestiflora, consists of a benzophenone skeleton with two
      attached pyran rings to which a cyclo-hexane ring and a C6 side chain are bonded.
      The benzene ring is significantly distorted from planarity (r.m.s. deviation =
      0.0007 A) due to the constraints imposed by junctions with the two pyran rings.
      The cyclo-hexane ring is in a chair conformation, one pyran ring is in a boat
      conformation, while the other is a distorted chair. The phenyl and benzene rings
      make a dihedral angle of 55.85 (9) degrees . An intra-molecular O-H?O hydrogen
      bond is observed. In the crystal, mol-ecules are linked via C-H?O inter-actions.

PMID- 22589955
TI  - (2E,4E)-Ethyl 5-(phenyl-sulfon-yl)penta-2,4-dienoate.
AB  - In the title compound, C(13)H(14)O(4)S, both C=C double bonds adopt an E
      conformation. In the crystal, mol-ecules are linked into centrosymmetric R(2)
      (2)(14) dimers via pairs of C-H?O hydrogen bonds.

PMID- 22589956
TI  - 4-(4-Fluoro-benzene-sulfonamido)-phenyl 4-fluoro-benzene-sulfonate.
AB  - In the title compound, C(18)H(13)F(2)NO(5)S(2), the complete mol-ecule is
      generated by a crystallographic inversion centre, and the O atom and the N-H
      group attached to the central ring are statistically disordered. The dihedral
      angle between the central and terminal benzene rings is 64.03 (6) degrees . In
      the crystal, N-H?O, C-H?F and C-H?O inter-actions link the mol-ecules into a
      three-dimensional network.

PMID- 22589957
TI  - 3-Acetyl-1,5-diphenyl-1H-pyrazole-4-carbonitrile.
AB  - The title compound, C(18)H(13)N(3)O, has a butterfly-like structure, in which the
      pyrazole ring forms dihedral angles of 59.31 (8) and 57.24 (8) degrees  with the
      two phenyl rings. The dihedral angle between the two phenyl rings is 64.03 (8)
      degrees . The pyrazole ring and the C-C=O plane of the acetyl group are twisted
      slightly, making a dihedral angle of 7.95 (18) degrees . In the crystal, mol
      ecules are linked through weak C-H?N and C-H?O inter-actions into a helical chain
      along the a-axis direction.

PMID- 22589958
TI  - 7-Benzyl-3-(4-fluoro-phen-yl)-2-propyl-amino-5,6,7,8-tetra-hydro
      pyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4(3H)-one.
AB  - In the title compound, C(25)H(25)FN(4)OS, the thienopyrimidine fused-ring system
      is close to planar (r.m.s. deviation = 0.0089 A), with a maximum deviation of
      0.0261 (17) A for the N atom adjacent to the benzene ring. This thienopyrimidine
      fused-ring system forms dihedral angles of 64.73 (3) and 81.56 (5) degrees  with
      the adjacent benzyl and fluoro-phenyl rings, respectively. Inter-molecular N-H?F
      and C-H?F hydrogen bonding, as well as C-F?pi inter-actions [F?centroid = 3.449
      (3) A; C-F?centroid = 91.87 (15) degrees ], help to stabilize the crystal
      structure.

PMID- 22589959
TI  - 4-[(2-Carb-oxy-eth-yl)amino]-benzoic acid monohydrate.
AB  - In the title compound, C(10)H(11)NO(4).H(2)O, the carboxyl group is twisted at a
      dihedral angle of 6.1 (3) degrees  with respect to the benzene ring. In the
      crystal, the organic mol-ecules are linked by pairs of O-H?O hydrogen bonds
      involving both carboxyl groups, forming zigzag chains propagating along the b
      axis direction. The water mol-ecules form [100] chains linked by O-H?O hydrogen
      bonds. The organic mol-ecule and water chains are cross-linked by N-H?O(water)
      and O(water)-H?O hydrogen bonds, generating (001) sheets.

PMID- 22589960
TI  - N,N'-Diethyl-N,N'-diphenyl-pyridine-2,6-dicarboxamide.
AB  - The asymmetric unit of the title compound, C(23)H(23)N(3)O(2), contains two mol
      ecules in both of which, one amide N atom is in a syn position with respect to
      the pyridine N atom, while the other amide N atom is in an anti position (the syn
      -anti conformation). There are minor conformational differences between the two
      mol-ecules, as reflected in the N(pyridine)-C-C-N(amide) torsion angles of -44.9
      (3) and 136.0 (2) degrees  for one mol-ecule and 43.5 (3) and -131.1 (2) degrees 
      for the other mol-ecule. However, the two mol-ecules show significant differences
      in the orientation of an ethyl group, with corresponding C-C-N-C torsion angles
      of 86.6 (3) degrees  for one mol-ecule and 79.6 (3) degrees  for the other mol
      ecule. In the crystal, mol-ecules are linked by weak C-H?O hydrogen bonds,
      forming a three-dimensional supra-molecular network.

PMID- 22589961
TI  - 5-(Prop-2-yn-yl)-5H-dibenzo[b,f]azepine.
AB  - The asymmetric unit of the title compound, C(17)H(13)N, contains two independent
      butterfly-shaped mol-ecules. The seven-membered azepine rings both adopt a boat
      conformation. The dihedral angles between the benzene rings in the two mol-ecules
      are 46.95 (11) and 52.21 (11) degrees .

PMID- 22589962
TI  - (3aR*,6S*,7aR*)-7a-Chloro-6-methyl-2-(4-methyl-phenyl-sulfon-yl)-2,3,3a,6,7,7a
      hexa-hydro-3a,6-ep-oxy-1H-isoindole.
AB  - In the title compound, C(16)H(18)ClNO(3)S, the six-membered ring has a boat
      conformation. The two five-membered rings with the bridging O atom adopt envelope
      conformations, whereas the N-containing five-membered ring adopts a twisted
      conformation. In the crystal, C-H?O hydrogen bonds link the mol-ecules into a
      three-dimensional network.

PMID- 22589963
TI  - (2-Oxo-2H-benzo[h]chromen-4-yl)methyl morpholine-4-carbodithio-ate.
AB  - In the title compound, C(19)H(17)NO(3)S(2), the morpholine ring is in a chair
      conformation. In the coumarin ring system, the dihedral angle between the benzene
      and pyran rings is 3.9 (1) degrees . In the crystal, weak C-H?O inter-actions
      link the mol-ecules into corrugated layers parallel to (102). The crystal packing
      also exhibits pi-pi inter-actions, with distances of 3.644 (1) and 3.677 (1) A
      between the centroids of the benzene rings of neighbouring mol-ecules.

PMID- 22589964
TI  - 4-[2-(Benzyl-amino)-phen-yl]-2,6-dimethyl-quinoline N-oxide.
AB  - The title compound, C(24)H(22)N(2)O, was obtained in a two-step procedure from
      the corresponding 4-(2-iodo-phen-yl)quinoline. The quinoline system is
      approximately planar [maximum deviation from the least-squares plane = 0.021 (2)
      A]. The planes of the quinoline system and the phenyl ring subtend a dihedral
      angle of 78.08 (8) degrees . In the crystal, pairs of mol-ecules are connected
      via a center of symmetry and linked by a pair of angular N-H?O hydrogen bond.
      These dimers form columns oriented along the c axis.

PMID- 22589965
TI  - (E)-Methyl 3-(3,4-dimeth-oxy-phen-yl)-2-[(1,3-dioxoisoindolin-2-yl)meth
      yl]acrylate.
AB  - In the title compound, C(21)H(19)NO(6), the isoindole ring system is essentially
      planar [maximum deviation = 0.019 (2) A for the N atom] and is oriented at a
      dihedral angle of 51.3 (1) degrees  with respect to the benzene ring. The two
      meth-oxy groups are almost coplanar with the attached benzene ring [C-O-C-C = 3.7
      (4) and 4.3 (4) degrees ]. The mol-ecular conformation is stabilized by an intra
      molecular C-H?O hydrogen bond, which generates an S(9) ring motif. In the
      crystal, mol-ecules are linked through bifurcated C-H?(O,O) hydrogen bonds having
      R(1) (2)(5) ring motifs, forming chains along the b-axis direction. The crystal
      packing is further stabilzed by pi-pi inter-actions [centriod-centroid distance =
      3.463 (1) A].

PMID- 22589966
TI  - 3,6-Dibromo-7-ethyl-amino-4-methyl-2H-chromen-2-one.
AB  - In title compound, C(12)H(11)Br(2)NO(2), the coumarin ring system is almost
      planar, the two rings being inclined to one another by 1.40 (15) degrees . There
      are two short intra-molecular inter-actions (N-H?Br and C-H?Br) involving the Br
      atoms. In the crystal, mol-ecules stack along the a-axis direction via pi-pi
      inter-actions; the centroid-centroid distances vary from 3.6484 (19) to 3.7942
      (19) A.

PMID- 22589967
TI  - 3-De-oxy-1,2-di-O-isopropyl-idene-5-O-tosyl-d-threo-pentofuran-ose.
AB  - In the crystal structure of the title compound, C(15)H(20)O(6)S, the two
      independent mol-ecules crystalllize in a chiral setting with two different
      conformations, twisted (4)T(3) and envelope (4)E, for the furan-ose rings. Weak C
      H?O contacts strengthen the crystal structure.

PMID- 22589968
TI  - Ethyl 5-(4-amino-phen-yl)isoxazole-3-carboxyl-ate.
AB  - The asymmetric unit of the title compound, C(12)H(12)N(2)O(3), contains two mol
      ecules in which the benzene and isoxazole rings are almost coplanar, the dihedral
      angles between their mean planes being 1.76 (9) and 5.85 (8) degrees . The two
      mol-ecules inter-act with each other via N-H?N and N-H?O hydrogen bonds, which
      link the mol-ecules into layers parallel to the ac plane. The layers stack in a
      parallel mode with an inter-layer distance of 3.36 (7) A.

PMID- 22589969
TI  - 9-(4-Bromo-but-yl)-9H-carbazole.
AB  - In the title compound, C(16)H(16)BrN, the bromo-butyl group lies on one side of
      the carbazole ring plane and has a zigzag shape. The dihedral angle between the
      two benzene rings is 0.55 degrees . In the crystal, mol-ecules are connected by
      van der Waals inter-actions.

PMID- 22589970
TI  - Pyrrolidin-1-ium 2-(naphthalen-1-yl)acetate-2-(naphthalen-1-yl)acetic acid (1/1).
AB  - In the title compound, C(4)H(10)N(+).C(12)H(9)O(2) (-).C(12)H(10)O(2), the
      pyrrolidine ring adopts an envelope conformation and the dihedral angle between
      the planes of the two naphthalene ring systems is 8.34 (10) degrees . The crystal
      structure is stabilized by O-H?O and N-H?O hydrogen bonds.

PMID- 22589971
TI  - N-[Amino(imino)methyl]uronium tetrafluoroborate.
AB  - In the title compound, C(2)H(7)N(4)O(+).BF(4) (-), inter-molecular N-H?O hydrogen
      bonds connect the cations into chains parallel to the c axis, with graph-set
      motif C(4). These chains are in turn connected into a three-dimensional network
      by inter-molecular N-H?F hydrogen bonds. The B-F distances distances in the anion
      are not equal.

PMID- 22589973
TI  - 7-Chloro-4-[(7-chloro-quinolin-4-yl)sulfan-yl]quinoline dihydrate.
AB  - In the title thio-ether dihydrate, C(18)H(10)Cl(2)N(2)S.2H(2)O, the S-bound
      quinolinyl residues are almost orthogonal, forming a dihedral angle of 72.36 (4)
      degrees . In the crystal, the four water mol-ecules are connected via an eight
      membered {?OH}(4) synthon with each of the four pendent water H atoms hydrogen
      bonded to a pyridine N atom to stabilize a three-dimensional architecture.

PMID- 22589972
TI  - 5-Amino-3-carb-oxy-1H-1,2,4-triazol-4-ium nitrate monohydrate.
AB  - The two-dimensional crystal packing of the title compound, C(3)H(5)N(4)O(2)
      (+).NO(2) (-).H(2)O, results from the stacking of well separated layers (i.e.
      with nothing between the layers) parallel to the (-113) plane in which adjacent
      cations adopt a head-to-head arrangement such that two -COOH groups are linked
      via two water mol-ecules (the water O atom behaves simultaneously as donor and
      acceptor of hydrogen bonds) and two -NH(2) groups are linked through two nitrate
      anions. This arrangement leads to alternating hydro-philic and hydro-phobic zones
      in which O-H?O and N-H?O hydrogen bonds, respectively, are observed.

PMID- 22589974
TI  - 3-Amino-1-(3,4-dimeth-oxy-phen-yl)-9,10-dihydro-phenanthrene-2,4-dicarbonitrile.
AB  - In the title compound, C(24)H(19)N(3)O(2), the partially saturated ring adopts a
      distorted half-chair conformation with the methyl-ene-C atom closest to the amino
      benzene ring lying 0.664 (3) A out of the plane defined by the five remaining
      atoms (r.m.s. deviation = 0.1429 A. The dihedral angle [32.01 (10) degrees ]
      between the benzene rings on either side of this ring indicates a significant
      fold in this part of the mol-ecule. The dimeth-oxy-substituted benzene ring is
      almost orthogonal to the benzene ring to which it is attached [dihedral angle =
      72.03 (9) degrees ]. The mol-ecule has been observed previously as the major
      component of a 1:19 co-crystal with 2-amino-4-(3,4-dimeth-oxy-phen-yl)-5,6
      dihydro-benzo[ha]quinoline-3-carbonitrile [Asiri et al. (2011). Acta Cryst. E67,
      o2873-o2873]. Supra-molecular chains with base vector [201] are formed in the
      crystal structure via N-H?O hydrogen bonds between the amino H atoms of one mol
      ecule inter-acting with the meth-oxy O atoms of a neighbouring mol-ecule. The
      chains are linked into a three-dimensional architecture by C-H?pi inter-actions.

PMID- 22589975
TI  - 3,6-Dimethyl-1-phenyl-1H,4H-pyrano[2,3-c]pyrazol-4-one.
AB  - The title compound, C(14)H(12)N(2)O(2), is almost planar with an r.m.s. deviation
      for all non-H atoms of 0.038 A. The observed planarity is rationalized in terms
      of a close intra-molecular C-H?O inter-action. Supra-molecular layers, two mol
      ecules thick and with a step topology, are formed in the crystal packing via C
      H?O contacts involving the carbonyl O atom, which accepts two such bonds, and pi
      pi inter-actions between the components of the fused ring system and the phenyl
      ring of inversion-related mol-ecules [centroid-centroid distances = 3.6819 (13)
      and 3.6759 (12) A].

PMID- 22589976
TI  - N,N-Dimethyl-4-[(E)-2-(3,6,7-tribromo-9-butyl-9H-carbazol-2-yl)ethen-yl]aniline.
AB  - In the title mol-ecule, C(26)H(25)Br(3)N(2), a dihedral angle of 6.15 (10)
      degrees  is present between the carbazole and benzene ring systems with an E
      conformation about the C=C bond [1.335 (4) A]. The butyl group is almost
      perpendicular to the carbazole plane [C-N-C-C torsion angle = -98.7 (3) degrees
      ]. In the crystal, supra-molecular double chains along [-7,18,-16] are formed via
      C-H?Br and pi-pi inter-actions [centroid(carbazole five-membered
      ring)?centroid(carbazole six-membered ring) distance = 3.6333 (13) A].

PMID- 22589977
TI  - 6,6-Dimethyl-2H,5H,6H,7H-1,3-dithiolo[4,5-f][1,5,3]dithia-silepin-2-one.
AB  - In the structure of the title compound, C(7)H(10)OS(4)Si, the carbonyl O atom
      lies in the plane of the five-membered dithiole ring with a deviation of only
      0.022 (2) A. The seven-membered ring adopts a chair conformation. The crystal
      packing is stabilized by S?O [3.096 (4) A] and S?S [3.620 (4) A] contacts,
      together with C-H?S inter-actions.

PMID- 22589978
TI  - Dimethyl-ammonium guanidinium naphthalene-1,5-disulfonate.
AB  - The asymmetric unit of the title salt, CH(6)N(3)
      (+).C(2)H(8)N(+).C(10)H(6)O(6)S(2) (2-), consists of one dimethyl-ammonium
      cation, one guanidinium cation, and two half naphthalene-1,5-disulfonate anions,
      which lie on inversion centers. N-H?O hydrogen bonds link the cations and anions
      into layers parallel to the ab plane. The layers have a sandwich-like structure,
      with the sulfonate groups and cations forming outer slices and the naphthalene
      ring systems inside.

PMID- 22589979
TI  - 5-Benzoyl-2-(1H-indol-3-yl)-4-(4-methyl-phen-yl)-4,5-dihydro-furan-3
      carbonitrile.
AB  - The furan ring in the title compound, C(27)H(20)N(2)O(2), adopts a twisted
      conformation about the sp(3)-sp(3) bond. The mol-ecular structure is stabilized
      by an intra-molecular C-H?O inter-action which generates an S(6) ring motif. The
      crystal packing is stabilized by N-H?O and C-H?O inter-actions generating
      centrosymmetric R(2) (2)(18) and C(6) chain motifs, respectively. A weak C-H?pi
      inter-action is also observed.

PMID- 22589980
TI  - 2,4-Bis(diphenyl-phosphan-yl)-1,1,2,3,3,4-hexa-phenyl-1,3-diphospha-2,4-dibora
      cyclo-butane tetra-hydro-furan sesqui-solvate.
AB  - In the title compound, C(60)H(50)B(2)P(4).1.5C(4)H(8)O, the diphospha-diborane
      mol-ecule lies on an inversion centre, whereas the disordered tetra-hydro-furan
      solvent mol-ecule is in a general position with a partial occupancy of 0.75. The
      diphosphadiborane mol-ecule consists of an ideal planar four-membered B(2)P(2)
      ring with an additional phenyl and a -PPh(2) group attached to each B atom.

PMID- 22589981
TI  - 5,7,13,15-Tetra-oxo-2,2,10,10-tetra-kis-(trifluoro-meth-yl)-4,8,12,16-tetra-oxa
      1(1,4),3(1,4),6(1,2),9(1,4),11(1,4),14(1,2)-hexa-benzenahexa-deca-phane tetra
      hydro-furan monosolvate.
AB  - The title compound, C(46)H(24)F(12)O(8).C(4)H(8)O, consists of a cyclic aryl
      ester dimer and a tetra-hydro-furan mol-ecule. In the structure of the cyclic
      dimer, one carbonyl group stretches above the cavity and the other below.

PMID- 22589982
TI  - Tetra-methyl N,N'-(2,2,3,3,4,4-hexa-fluoro-1,5-dioxopentane-1,5-di-yl)bis
      (phospho-ramidate).
AB  - The mol-ecule of the title compound, C(9)H(14)F(6)N(2)O(8)P(2), lies on a twofold
      rotation axis that passes through the middle C atom of the three-atom fluoro
      methyl-ene unit. The carbonyl and phosphoryl groups are in an antiperiplanar
      conformation. In the crystal, N-H?O=P hydrogen bonds link the mol-ecules into
      polymeric chains parallel to the c axis.

PMID- 22589983
TI  - (4R*,5R*)-Diethyl 2-(4-nitro-phen-yl)-1,3-dioxolane-4,5-dicarboxyl-ate.
AB  - In the title compound, C(15)H(17)NO(8), the nitro group is essentially coplanar
      with the aromatic ring [dihedral angle = 6.4 (3) A]. The five-membered ring has a
      twist conformation. In the crystal, C-H?O inter-actions link the mol-ecules into
      a helical chain propagating along [010].

PMID- 22589984
TI  - N-(2,2-Dimethyl-propano-yl)-N'-(2-meth-oxy-phen-yl)thio-urea.
AB  - In the title compound, C(13)H(18)N(2)O(2)S, the carbonyl-thio-urea fragment is
      nearly planar with an r.m.s. deviation of 0.0096 A. The dihedral angle between
      carbonyl-thio-urea group and the benzene ring is 19.16 (16) degrees . There are
      two intra-molecular N-H?O hydrogen bonds, which lead to two pseudo-six-membered
      rings. Weak intra-molecular C-H?S hydrogen bonding also occurs.

PMID- 22589985
TI  - (E)-N-Benzyl-ideneadamantan-1-amine.
AB  - In the title compound, C(17)H(21)N, the dihedral angle between the benzene ring
      and the imine group (-N=) is 5.1 (4) degrees . In the adamantane group, the C-C-C
      bond angles range from 107.88 (19) to 111.33 (17) degrees . Only weak van der
      Waals inter-actions contribute to the contribute to the packing of the molecules
      in the crystal..

PMID- 22589987
TI  - 1-Benzyl-1H-benzotriazole.
AB  - In the title compound, C(13)H(11)N(3), the benzotriazole ring system is
      essentially planar, with a maximum deviation of 0.0173 (18) A, and forms a
      dihedral angle of 75.08 (8)A with the phenyl ring. In the crystal, pairs of weak
      C-H?N hydrogen bonds form inversion dimers. In addition, there are weak C
      H?pi(arene) inter-actions and weak pi-pi stacking inter-actions, with a centroid
      centroid distance of 3.673 (11) A.

PMID- 22589986
TI  - 5,6-Dimethyl-4-phenyl-2H-pyran-2-one.
AB  - In the title compound, C(13)H(12)O(2), the dihedral angle between the pyran-one
      and phenyl rings is 57.55 (9) degrees . In the crystal, the mol-ecules are linked
      by pi-pi stacking inter-actions between the parallel pyran-one rings of
      neighboring mol-ecules with distances of 3.5778 (11) A and 3.3871 (11) A between
      the planes. C-H?O interactions also occur.

PMID- 22589988
TI  - Methyl 2,2-dimeth-oxy-5,5-bis-(methyl-sulfan-yl)-3-oxopent-4-enedithio-ate.
AB  - In the title mol-ecule, C(10)H(16)O(3)S(4), a short intra-molecular S?O(=C)
      distance [2.726 (2) A] indicates the presence of a nonbonding attractive inter
      action. In the crystal, mol-ecules are linked into centrosymmetric dimers via
      weak inter-molecular C-H?O and S?S [3.405 (3) A] inter-actions. These dimers are
      linked by further weak C-H?O inter-actions into columns along the a axis.

PMID- 22589989
TI  - Dimethyl 2,6-dimethyl-4-(3-phenyl-1H-pyrazol-4-yl)-1,4-dihydro-pyridine-3,5
      dicarboxyl-ate.
AB  - In the title compound, C(20)H(21)N(3)O(4), the 1,4-dihydro-pyridine ring adopts a
      boat conformation. An intra-molecular C-H?O hydrogen bond generates an S(6) ring
      motif. The pyrazole ring makes dihedral angles of 87.81 (7) and 45.09 (7) degrees
      with the mean plane of the 1,4-dihydro-pyridine ring and the phenyl ring,
      respectively. In the crystal, mol-ecules are linked by N-H?N, N-H?O and C-H?O
      hydrogen bonds into a three-dimensional network.

PMID- 22589990
TI  - 3,3'-[1,2-Phenyl-enebis(methyl-ene)]bis-(1-octylbenzimidazolium) dibromide
      monohydrate.
AB  - In the title hydrated mol-ecular salt, C(38)H(52)N(4) (2+).2Br(-).H(2)O, the
      central benzene ring of the dication makes dihedral angles of 89.47 (13) and
      72.69 (12) degrees  with the pendant benzimidazol-3-ium rings. The conformations
      of the octyl side chains are completely different. In the crystal, the components
      are linked by O-H?Br, C-H?Br and C-H?O hydrogen bonds into a two-dimensional
      network lying parallel to the ac plane. Aromatic pi-pi stacking inter-actions are
      also observed [shortest centroid-to-centroid separation = 3.5047 (16) A].

PMID- 22589991
TI  - (1Z,2E)-N'-{2-Chloro-1-methyl-2-[2-(4-methyl-phen-yl)hydrazin-1-yl-idene]ethyl
      idene}-4-meth-oxy-benzohydrazide.
AB  - The asymmetric unit of the title compound, C(18)H(19)ClN(4)O(2), contains two mol
      ecules, in which the dihedral angles between the benzene rings are 43.60 (12) and
      58.65 (13) degrees . The hydrazine N atoms are twisted slightly out of the planes
      of the tolyl and meth-oxy-benzene rings: the C-C-N-N and N-N-C-C torsion angles
      are 171.1 (2) and -174.4 (2) degrees , respectively, for one mol-ecule and -177.4
      (2) and -170.6 (2) degrees , respectively, for the other. In the crystal, mol
      ecules are linked by N-H?O and C-H?O hydrogen bonds into chains propagating along
      the b-axis direction.

PMID- 22589992
TI  - Absolute configuration of (1S,2S)-3-methyl-2-phenyl-2,3-dihydro-thia-zolo[2,3
      b]quinazolin-5-one.
AB  - The absolute structure of the molecule in the crystal of the title compound,
      C(17)H(14)N(2)OS, was determined by the refinement of the Flack parameter to 0.0
      (2) based on 1011 Friedel pairs. The quinazoline ring is essentially planar, with
      a maximum deviation of 0.037 (2) A. The thia-zole ring is distorted from
      planarity [maximum deviation = 0.168 (2) A] and adopts a slightly twisted
      envelope conformation, with the C atom as the flap atom. The central thia-zole
      ring makes dihedral angles of 7.01 (8) and 76.80 (10) degrees  with the
      quinazoline and phenyl rings, respectively. The corresponding angle between the
      quinazoline and phenyl rings is 3.74 (9) degrees . In the crystal, there are no
      classical hydrogen bonds but stabilization is provided by weak C-H?pi inter
      actions, involving the centroids of the phenyl rings.

PMID- 22589993
TI  - 4-Meth-oxy-benzoyl-meso-octa-methyl-calix[2]pyrrolidino[2]pyrrole: an acyl
      chloride derivative of a partially reduced calix[4]pyrrole.
AB  - In the title compound, C(36)H(50)N(4)O(2), the two pyrrolidine rings have
      envelope conformations. The conformation of the macrocycle is stabilized by N-H?N
      hydrogen bonds and a C-H?N inter-action. The benzoyl ring is inclined to an
      adjacent pyrrole ring by 6.76 (9) degrees , with a centroid-to-centroid distance
      of 3.6285 (10) A. In the crystal, apart from a C-H?O and a C-H?pi inter-action,
      mol-ecules are linked via an N-H?O hydrogen bond, leading to the formation of
      helical chains propagating along [010].

PMID- 22589995
TI  - 9-(Dicyano-methyl-idene)fluorene-tetra-thia-fulvalene (1/1).
AB  - The title compound, C(16)H(8)N(2).C(6)H(4)S(4), crystallizes with the fluorene
      derivative placed in a general position and two half tetra-thia-fulvalene (TTF)
      mol-ecules, each completed to a whole mol-ecule through an inversion center. The
      fluorene ring system is virtually planar (r.m.s. deviation from the mean plane =
      0.027 A) and the dicyano group is twisted from the fluorene plane by only 3.85
      (12) degrees . The TTF mol-ecules are also planar, and their central C=C bond
      lengths [1.351 (8) and 1.324 (7) A] compare well with the same bond length in
      neutral TTF (ca 1.35 A). These features indicate that no charge transfer occurs
      between mol-ecules in the crystal; the compound should thus be considered a
      cocrystal rather than an organic complex. This is confirmed by the crystal
      structure, in which no significant stacking inter-actions are observed between
      mol-ecules.

PMID- 22589994
TI  - Ethyl 3-[7-eth-oxy-6-(4-meth-oxy-benzene-sulfonamido)-2H-indazol-2-yl]propano
      ate.
AB  - In the title compound, C(21)H(25)N(3)O(6)S, the dihedral angle between the meth
      oxy-benzene and indazole rings is 74.96 (5) degrees . The crystal packing is
      stabilized by an N-H?O hydrogen bond into a two-dimensional network. In addition,
      C-H?pi inter-actions and a pi-pi contact, with a centroid-centroid distance of
      3.5333 (6) A, are observed. The crystal packing is stabilized by N-H?O and C-H?O
      hydrogen bonds.

PMID- 22589996
TI  - 2,2'-Dichloro-N,N'-[1,3-phenyl-enebis(methyl-ene)]diacetamide.
AB  - The complete mol-ecule of the title compound, C(12)H(14)Cl(2)N(2)O(2), is
      generated by a crystallographic twofold axis with two C atoms of the central
      benzene ring lying on the axis. In the crystal, N-H?O hydrogen bonds link the mol
      ecules into chains parallel to the c axis.

PMID- 22589997
TI  - (E)-3-(2-Chloro-phen-yl)-2-[(2-formylphen-oxy)meth-yl]prop-2-ene-nitrile.
AB  - In the title compound, C(17)H(12)ClNO(2), the dihedral angle between the two
      benzene rings is 42.9 (1) degrees . There are no sgnificant inter-molecular inter
      actions.

PMID- 22589998
TI  - 4-[5-Amino-4-(4-fluoro-phen-yl)-3-(pyridin-4-yl)-1H-pyrazol-1-yl]benzo-nitrile.
AB  - In the crystal structure of the title compound, C(21)H(14)FN(5), the pyrazole
      ring forms dihedral angles of 38.0 (1), 40.0 (1) and 28.5 (1) degrees  with the
      directly attached 4-fluoro-phenyl, pyridine and benzonitrile rings, respectively.
      The crystal packing is characterized by N-H?N hydrogen bonds, which result in a
      two-dimensional network parallel to the ac-plane.

PMID- 22589999
TI  - Diisopropyl {[(R)-2-(2-amino-6-chloro-9H-purin-9-yl)-1-methyl-eth-oxy]meth-yl}
      phospho-nate.
AB  - In the title compound, C(15)H(25)ClN(5)O(4)P, the r.m.s. deviation for the purine
      ring system is 0.0165 A. The coordination about the P atom is a distorted
      tetrahedron [O=P-O angles = 116.70 (6) and 109.87 (6) degrees ]. In the crystal,
      molecules are linked by N-H?O hydrogen bonds, generating a three-dimensional
      network.

PMID- 22590000
TI  - 4-Chloro-N-methyl-benzamide.
AB  - There are two mol-ecules in the asymmetric unit of the title compound,
      C(8)H(8)ClNO, which are linked in the crystal structure via N-H?O hydrogen bonds
      into chains along the b axis. C-H?O contacts also occur. The benzene ring makes
      dihedral angles of 5.9 (1) and 16.7 (1) degrees with the attached amide group in
      the two independent molecules.

PMID- 22590001
TI  - 2-(Piperidin-1-yl)-6-(1H-pyrrol-1-yl)pyridine-3,5-dicarbonitrile.
AB  - The piperidine ring of the title compound, C(16)H(15)N(5), adopts a chair
      conformation. The pyridine ring is essentially planar, with a maximum deviation
      of 0.035 (3) A. The pyrrole and pyridine rings are almost coplanar, forming a
      dihedral angle of 3.48 (14) degrees . In the crystal, no classical hydrogen bonds
      were found. In the crystal, the molecules are linked by aromatic pi-pi stacking
      [centroid-centroid separations = 3.4984 (16) and 3.9641 (15) A between pyrrole
      and pyridine rings and between pyridine rings, respectively].

PMID- 22590002
TI  - 6-[(2E)-3,7-Dimethyl-octa-2,6-dien-1-yl]-5,7-dihy-droxy-8-(2-methyl-butano-yl)-4
      phenyl-2H-chromen-2-one-6-[(2E)-3,7-dimethyl-octa-2,6-dien-1-yl]-5,7-dihy-droxy-8
      (3-methyl-butano-yl)-4-phenyl-2H-chromen-2-one (1/1) from Mesua elegans.
AB  - The title co-crystal, C(30)H(34)O(5).C(30)H(34)O(5), comprises a 1:1 mixture of
      two mostly superimposed mol-ecules with the same chemical formula that differ in
      the nature of the substituent (2-methyl-butanoyl or 3-methyl-butano-yl) bound at
      the exocyclic ketone. The lactone ring is close to planar (r.m.s. deviation =
      0.058 A) and the phenyl ring is twisted out of this plane [dihedral angle = 60.08
      (9) degrees ]. The geranyl substituent is almost normal to benzene ring to which
      it is connected [C-C-C(ar)-C(ar) (ar = aromatic) torsion angle = -87.8 (2)
      degrees ]. Intra-molecular O-H?O and O-H?pi inter-actions are formed. In the
      crystal, supra-molecular chains are formed along the a axis owing to C-H?O
      contacts, with the lactone carbonyl atom accepting two such bonds.

PMID- 22590003
TI  - 5-(Phenyl-diazen-yl)tropolone.
AB  - THE TITLE COMPOUND [SYSTEMATIC NAME: (E)-2-hy-droxy-5-(phenyl-diazen-yl)cyclo
      hepta-2,4,6-trien-1-one], C(13)H(10)N(2)O(2), is essentially planar with an
      r.m.s. deviation of 0.036 (2) A and a dihedral angle of 1.57 (8) degrees  between
      the phenyl and tropolone rings. In the crystal, mol-ecules are linked by pairs of
      O-H?O hydrogen bonds into inversion dimers. The dimers are further connected by C
      H?O hydrogen bonds and pi-pi stacking inter-actions, with centroid-centroid
      distances of 3.6934 (9) and 3.6282 (9) A.

PMID- 22590004
TI  - 3-(3-Chloro-phenyl-sulfon-yl)-5-isopropyl-2-methyl-1-benzofuran.
AB  - In the title compound, C(18)H(17)ClO(3)S, the 3-chloro-benzene ring makes a
      dihedral angle of 82.04 (5) degrees  with the mean plane [r.m.s. deviation =
      0.006 (1) A] of the benzofuran fragment. In the crystal, mol-ecules are linked by
      weak C-H?O and C-H?pi inter-actions.

PMID- 22590005
TI  - 3-(3-Chloro-phenyl-sulfin-yl)-2,5,7-trimethyl-1-benzofuran.
AB  - In the title compound, C(17)H(15)ClO(2)S, the 3-chloro-phenyl ring makes a
      dihedral angle of 84.48 (4) degrees  with the mean plane [r.m.s. deviation =
      0.004 (1) A] of the benzofuran fragment. In the crystal, mol-ecules are linked by
      weak C-H?O, C-H?pi and C-S?pi [3.414 (2) A] inter-actions. The crystal structure
      also exhibits weak pi-pi inter-actions between the furan rings of neighbouring
      mol-ecules [centroid-centroid distance = 3.826 (2), inter-planar distance = 3.447
      (2) and slippage = 1.660 (2) A].

PMID- 22590006
TI  - 5-Cyclo-hexyl-2-(3-fluoro-phen-yl)-3-methyl-sulfinyl-1-benzofuran.
AB  - In the title compound, C(21)H(21)FO(2)S, the cyclo-hexyl ring adopts a chair
      conformation. The 3-fluoro-phenyl ring makes a dihedral angle of 38.38 (6)
      degrees  with the mean plane [r.m.s. deviation = 0.010 (1) A] of the benzofuran
      fragment. In the crystal, mol-ecules are linked by weak C-H?O hydrogen bonds.

PMID- 22590007
TI  - 3-(3-Chloro-phenyl-sulfon-yl)-2,5,7-trimethyl-1-benzofuran.
AB  - In the title compound, C(17)H(15)ClO(3)S, the 3-chloro-phenyl ring makes a
      dihedral angle of 77.76 (6) degrees  with the mean plane [r.m.s. deviation =
      0.007 (1) A] of the benzofuran fragment. In the crystal, mol-ecules are linked by
      weak inter-molecular C-H?O and C-H?pi inter-actions.

PMID- 22590008
TI  - 2-(5-Fluoro-3-isopropyl-sulfanyl-7-methyl-1-benzofuran-2-yl)acetic acid.
AB  - The title compound, C(14)H(15)FO(3)S, was prepared by alkaline hydrolysis of
      ethyl 2-(5-fluoro-3-isopropyl-sulfanyl-7-methyl-1-benzofuran-2-yl)acetate. In the
      crystal, mol-ecules are linked via pairs of O-H?O hydrogen bonds, forming
      inversion dimers. These dimers are connected by weak C-H?O hydrogen bonds.

PMID- 22590009
TI  - 5-Cyclo-hexyl-2-methyl-3-(4-methyl-phenyl-sulfin-yl)-1-benzofuran.
AB  - In the title compound, C(22)H(24)O(2)S, the cyclo-hexyl ring adopts a chair
      conformation. The 4-methyl-phenyl ring makes a dihedral angle of 81.60 (5)
      degrees  with the mean plane [r.m.s. deviation = 0.004 (1) A] of the benzofuran
      fragment. In the crystal, mol-ecules are linked by weak C-H?O hydrogen bonds and
      weak pi-pi inter-actions between the furan rings of adjacent mol-ecules [centroid
      centroid distance = 3.545 (2) A, inter-planar distance = 3.489 (2) A and slippage
      = 0.628 (2) A.

PMID- 22590010
TI  - (R)-1,1'-Binaphthalene-2,2'-diol-(Z)-N-ethyl-ideneethanamine N-oxide (1/1).
AB  - In the title compound, C(4)H(9)NO.C(20)H(14)O(2), the dihedral angle between the
      naphthalene ring systems of the binaphthalene-diol mol-ecule is 77.53 (14)
      degrees . In the crystal, the two components are linked by O-H?O hydrogen bonds,
      forming a zigzag chain along the c axis.

PMID- 22590011
TI  - 2-Methyl-sulfanyl-5,6-dihydro-2H-1,3-dithiolo[4,5-b][1,4]dioxin-2-ium tetra
      fluoro-borate.
AB  - The title compound, C(6)H(7)O(2)S(3) (+).BF(4) (-), consists of a planar 2-thioxo
      1,3-dithiol-4,5-yl unit [maximum deviation from the ring plane = 0.020 (3) A],
      with an ethyl-enedi-oxy group fused at the 4,5-positions; the ethyl-enedi-oxy C
      atoms are disordered over two positions with site-occupancy factors of 0.5. The
      1,4-dioxine ring has a twist-chair conformation. Weak cation-anion S?F inter
      actions [3.022 (4)-3.095 (4) A] and an S?O [3.247 (4) A] inter-action are
      present.

PMID- 22590012
TI  - N,N'-[1,3-Phenyl-enebis(methyl-ene)]di-p-toluenesulfonamide.
AB  - In the title compound, C(22)H(24)N(2)O(4)S(2), the dihedral angles between the
      central benzene ring and the pendant rings are 66.96 (13) and 69.37 (13) degrees
      . The torsion angles for the C-N-S-C fragments are -68.5 (3) and -72.6 (3)
      degrees . In the crystal, mol-ecules are linked by N-H?O hydrogen bonds to
      generate infinite (001) sheets containing R(4) (4)(28) loops. A weak aromatic pi
      pi stacking contact between one of the terminal benzene rings and its inversion
      related partner is also observed [centroid-to-centroid separation = 3.796 (2) A
      and slippage = 1.581 A], as are two possible C-H?pi contacts.

PMID- 22590013
TI  - N-(4-Chloro-3-nitro-phen-yl)succinamic acid.
AB  - In the title compound, C(10)H(9)ClN(2)O(5), the nitro group is significantly
      twisted out of the plane of the benzene ring to which it is attached [dihedral
      angle = 27.4 (6) degrees ]. In the crystal, mol-ecules are linked into
      centrosymmetric dimers via pairs of O-H?O hydrogen bonds. These dimers are
      further linked by N-H?O hydrogen bonds into double chains running along the a
      axis.

PMID- 22590014
TI  - 2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl 4-fluoro-benzoate.
AB  - In the title compound, C(13)H(12)FN(3)O(4), the dihedral angle between the
      benzene and imidazole rings is 32.77 (12) degrees . In the crystal, mol-ecules
      are linked into a three-dimensional network by C-H?O hydrogen bonds.

PMID- 22590015
TI  - (Z)-N-Methyl-2-(5-nitro-2-oxoindolin-3-yl-idene)hydrazinecarbothio-amide.
AB  - In the title compound, C(10)H(9)N(5)O(3)S, an intra-molecular N-H?O hydrogen bond
      generates an S(6) ring motif. In the crystal, mol-ecules are linked via N-H?S
      hydrogen bonds into a zigzag chain along the b axis. C-H?O inter-actions are
      observed between the chains.

PMID- 22590016
TI  - (Z)-N-Methyl-2-(5-methyl-2-oxoindolin-3-yl-idene)hydrazinecarbothio-amide.
AB  - In the title compound, C(11)H(12)N(4)OS, an intra-molecular N-H?O hydrogen bond
      generates an S(6) ring motif. In the crystal, the mol-ecules form a helical chain
      along the a axis through an N-H?O hydrogen bond. These chains are extended by an
      N-H?S hydrogen bond and a C-H?pi inter-action into a three-dimensional network.

PMID- 22590017
TI  - 2-(4-Nitro-benzyl-idene)malononitrile.
AB  - In the title compound, C(10)H(5)N(3)O(2), the benzyl-idene-malono-nitrile unit is
      nearly planar, with a maximum deviation of 0.129 (2) A for a terminal N atom; the
      nitro group is approximately coplanar with the benzene ring [dihedral angle = 8.8
      (3) degrees ]. An intra-molecular C-H?N hydrogen bond stabilizes the mol-ecular
      conformation.

PMID- 22590018
TI  - N-Cyclo-pentyl-N-(3-oxo-2,3-dihydro-1H-inden-1-yl)acetamide.
AB  - The title mol-ecule, C(16)H(19)NO(2), consists of an indane moiety, which is
      connected through an N atom to an acetamide group and a cyclo-pentane ring. The N
      atom adopts planar triangular geometry. Inter-molecular inter-actions, such as pi
      pi stacking or hydrogen bonding, were not observed.

PMID- 22590019
TI  - 4-Chloro-anilinium 3-carb-oxy-prop-2-enoate.
AB  - In the title compound, C(6)H(7)ClN(+).C(4)H(3)O(4) (-), the cations and anions
      lie on mirror planes and hence only half of the mol-ecules are present in the
      asymmeric unit. The 4-chloro-anilinium cation and hydrogen maleate anion in the
      asymmetric unit are each planar and are oriented at an angle of 15.6 (1) degrees 
      to one another and perpendicular to the b axis. A characterestic intra-molecular
      O-H?O hydrogen bond, forming an S(7) motif, is observed in the maleate anion. In
      the crystal, the cations and anions are linked by N-H?O hydrogen bonds, forming
      layers in the ab plane. The aromatic rings of the cations are sandwiched between
      hydrogen-bonded chains and rings formed through the amine group of the cation and
      maleate anions, leading to alternate hydro-phobic (z = 0 or 1) and hydro-philic
      layers (z = 1/2) along the c axis.

PMID- 22590020
TI  - 2-(2H-1,3-Benzodioxol-5-yl)-1,3-benzo-thia-zole.
AB  - In the title compound, C(14)H(9)O(2)S, the benzothia-zole unit is oriented at a
      dihedral angle of 7.1 (1) degrees  with respect to the benzodioxole unit. The
      dioxole ring adopts flattened envelope conformation with the methyl-ene C atom at
      the flap. The crystal packing is stabilized by pi-pi inter-actions [centroid
      centroid distances = 3.705 (1) and 3.752 (1) A], C-H?pi inter-actions and a short
      S?S contact of 3.485 (1) A.

PMID- 22590022
TI  - 2-(2,5-Dimeth-oxy-phen-yl)-N-[2-(4-hy-droxy-phen-yl)eth-yl]acetamide.
AB  - In the title compound, C(18)H(21)NO(4), the dihedral angles between the acetamide
      group and the meth-oxy- and hy-droxy-substitured benzene rings are 80.81 (5) and
      8.19 (12) degrees , respectively. The benzene rings are twisted with respect to
      each other, making a dihedral angle of 72.89 (5) degrees . In the crystal, N-H?O
      and O-H?O hydrogen bonds link the mol-ecules into a three-dimensional network.

PMID- 22590021
TI  - (Z)-2-(2-Oxoindolin-3-yl-idene)-N-phenylhydrazinecarbothio-amide.
AB  - In the title compound, C(15)H(12)N(4)OS, the dihedral angle between the nine
      membered indolin-2-one ring system and the phenyl ring is 2.72 (7) degrees .
      Intra-molecular cyclic N-H?O and C-H?S hydrogen-bonding inter-actions [graph set
      S(6)] are present, as are weak N-H?N inter-actions [graph set S(5)]. In the
      crystal, mol-ecules form centrosymmetric cyclic dimers through pairs of N-H?O
      hydrogen bonds [graph set R(2) (2)(8)] and these are extended by C-H?S inter
      actions. The crystal structure also features weak C-H?pi inter-actions.

PMID- 22590023
TI  - (E)-N'-(5-Chloro-2-hy-droxy-benzyl-idene)-2,4-dihy-droxybenzohydrazide methanol
      monosolvate.
AB  - In the title compound, C(14)H(11)ClN(2)O(4).CH(3)OH, the mol-ecule adopts an E
      conformation about the C=N bond. The compound is in the enamine-keto form. The
      two terminal benzene rings make a dihedral angle of 10.53 (9) degrees . Intra-mol
      ecular O-H?O and O-H?N hydrogen bonding stabilizes the mol-ecular structure. In
      the crystal, O-H?O hydrogen bonds link the mol-ecules, forming chains running
      along the b axis.

PMID- 22590024
TI  - 4-[Bis(4-fluoro-phen-yl)meth-yl]piperazin-1-ium bis-(trichloro-acetate) 0.4
      hydrate.
AB  - The title compound, C(17)H(20)F(2)N(2) (2+).2C(2)Cl(3)O(2) (-).0.4H(2)O, has
      twofold protonated N atoms. The trichloro-acetate anions each show one disordered
      Cl atom with site occupation factors of 0.945 (7):0.055 (7) 0.945 (8):0.055 (8).
      In the crystal, N-H?O, O(water)-H?O and O(water)-H?F inter-actions connect the
      components into a three-dimensional network.

PMID- 22590025
TI  - 4-[(Z)-(n-Butyl-amino)(phenyl)methyl-idene]-3-methyl-1-phenyl-1H-pyrazol-5(4H)
      one.
AB  - The title compound, C(21)H(23)N(3)O, exists in an enamine-keto form with the
      amino group involved in an intra-molecular N-H?O hydrogen bond. The dihedral
      angle between the phenyl rings is 73.59 (6) degrees . The five-membered ring is
      nearly planar, the largest deviation being 0.0004 (7) A, and makes dihedral
      angles of 4.81 (6) and 69.81 (5) degrees  wth the phenyl rings. In the crystal,
      pairs of weak C-H?O inter-actions link the mol-ecules into centrosymmetric
      dimers.

PMID- 22590026
TI  - 1-(2-Hy-droxy-eth-yl)pyrrole-2,5-dione.
AB  - The asymmetric unit of the title compound, C(6)H(7)NO(3), contains two mol-ecules
      (A and B) related by a non-crystallographic twofold pseudo-axis. The mol-ecules
      are joined in the (AABB)(n) manner by O-H?O hydrogen bonds between their hy-droxy
      groups, thus forming C(2) chains along the a-axis direction. Neighboring mol
      ecules of the same kind (A and A, or B and B) are related by inversion centers,
      so that all hy-droxy H atoms are disordered other two sets of sites with half
      occupancies (superimposed O-H?O and O?H-O fragments). The mol-ecules are further
      linked by C-H?O inter-actions, which can be considered to be weak hydrogen bonds.

PMID- 22590027
TI  - 5-Meth-oxy-1-[(5-meth-oxy-1H-indol-2-yl)meth-yl]-1H-indole.
AB  - In the title compound, C(19)H(18)N(2)O(2), the two indole ring systems are
      essentially planar [maximum deviation = 0.015 (2) A in both indole ring systems]
      and make a dihedral angle of 72.17 (7) degrees  with each other. In the crystal,
      the mol-ecules are linked into a zigzag chain along the a axis via N-H?O hydrogen
      bonds.

PMID- 22590028
TI  - 4-[3-(Biphenyl-4-yl)-1-phenyl-4,5-di-hydro-1H-pyrazol-5-yl]-3-(4-meth-oxy-phen
      yl)-1-phenyl-1H-pyrazole dioxane monosolvate.
AB  - In the title compound, C(37)H(30)N(4)O.C(4)H(8)O(2), the dihedral angle between
      the pyrazole and dihydro-pyrazole rings is 74.09 (10) degrees . In the crystal,
      the components are linked into centrosymmetric tetra-mers (two main mol-ecules
      and two solvent mol-ecules) by C-H?O hydrogen bonds. C-H?pi and pi-pi [shortest
      centroid-centroid separation = 3.6546 (9) A] inter-actions are also observed.

PMID- 22590029
TI  - (2E)-3-(3-Nitro-phen-yl)-1-[4-(piperidin-1-yl)phen-yl]prop-2-en-1-one.
AB  - In the title compound, C(20)H(20)N(2)O(3), the piperidine ring adopts a chair
      conformation and its mean plane forms dihedral angles of 19.63 (9) and 19.44 (9)
      degrees , respectively, with the benzene and the nitro-substituted benzene ring.
      The benzene and nitro-substituted benzene rings are almost coplanar and make a
      dihedral angle of 4.78 (8) degrees . In the crystal, mol-ecules are linked by C
      H?O hydrogen bonds into two-dimensional networks parallel to the ab plane. The
      crystal packing is further stabilized by pi-pi inter-actions [maximum centroid
      centroid distance = 3.7807 (12) A].

PMID- 22590030
TI  - 1-[3-(4-Chloro-phen-yl)-5-(4-meth-oxy-phen-yl)-4,5-dihydro-1H-pyrazol-1-yl]butan
      1-one.
AB  - In the title compound, C(20)H(21)ClN(2)O(2), the benzene rings form dihedral
      angles of 6.35 (5) and 81.82 (5) degrees  with the mean plane of the 4,5-dihydro
      1H-pyrazole ring (r.m.s. deviation = 0.145 A). This latter ring adopts an
      envelope conformation with the CH grouping as the flap. The dihedral angle
      between the benzene rings is 75.63 (4) degrees . In the crystal, mol-ecules are
      linked by C-H?Cl and C-H?O hydrogen bonds into chains along [-201]. The crystal
      structure also features C-H?pi inter-actions.

PMID- 22590031
TI  - 4-Chloro-benzoyl-meso-octa-methyl-calix[2]pyrrolidino[2]pyrrole: an acyl chloride
      derivative of a partially reduced calix[4] pyrrole.
AB  - In the title compound, C(35)H(47)ClN(4)O, the two pyrrolidine rings have envelope
      conformations. The conformation of the macrocycle is stabilized by N-H?N hydrogen
      bonds and a C-H?N inter-action. The benzoyl ring is inclined to the adjacent
      pyrrole ring by 11.66 (11) degrees , with a centroid-centroid distance of 3.7488
      (13) A. In the crystal, molecules are linked by N-H?O hydrogen bonds into helical
      chains propagating in [010] and C-H?O and C-H?pi interactions are also observed.

PMID- 22590032
TI  - 3-[Hy-droxy(3-meth-oxy-phen-yl)methyl-idene]-2-(2-oxo-2-phenyl-eth-yl)-3,4
      dihydro-2H-1lambda(6),2-benzothia-zine-1,1,4-trione.
AB  - In the title mol-ecule, C(24)H(19)NO(6)S, the heterocyclic thia-zine ring adopts
      a half-chair conformation with the S and N atoms displaced by 0.180 (5) and 0.497
      (5) A, respectively, on opposite sides of the mean plane formed by the remaining
      ring atoms. The benzene rings of the benzothia-zine unit and the meth-oxy-phenyl
      group are almost coplanar, with the dihedral angle between the mean planes of
      these rings being 5.9 (2) degrees , while the benzene ring of the 2-oxo-2-phenyl
      ethyl group is inclined at 79.68 (11) and 81.01 (10) degrees , respectively, to
      these rings. The mol-ecular structure is consolidated by intra-molecular O-H?O
      and C-H?N inter-actions, and the crystal packing is stabilized by weak C-H?O
      hydrogen bonds.

PMID- 22590033
TI  - 2-[2-(3-Chloro-phen-yl)-2-oxoeth-yl]-4-hy-droxy-3-(3-meth-oxy-benzo-yl)-2H
      1lambda(6),2-benzothia-zine-1,1-dione.
AB  - In the title mol-ecule, C(24)H(18)ClNO(6)S, the heterocyclic thia-zine ring
      adopts a half chair conformation with the S and N atoms displaced by 0.318 (3)
      and 0.387 (3) A, respectively, on the opposite sides from the mean plane formed
      by the remaining ring atoms. The benzene rings of the benzothia-zin unit and meth
      oxy-benzoyl group are more or less coplanar, the dihedral angle between the mean
      planes of these rings being 12.37 (10) degrees  while the chloro-phenyl ring is
      inclined at 81.87 (4) and 73.30 (5) degrees , respectively, to these rings. The
      mol-ecular structure is consolidated by intra-molecular O-H?O and C-H?N inter
      actions and the crystal packing is stabilized by weak inter-molecular C-H?O
      hydrogen bonds.

PMID- 22590034
TI  - N-(2,6-Dimethylphenyl)-N'-propanoyl-thiourea.
AB  - In the title compound, C(12)H(16)N(2)OS, an intra-molecular N-H?O hydrogen bond
      forms an S(6) ring motif. The propionyl-thio-urea group is approximately planar
      [with a maximum deviation of 0.135 (2) A] and forms a dihedral angle of 83.39 (7)
      degrees  with the benzene ring. In the crystal, mol-ecules are linked by pairs of
      N-H?S hydrogen bonds, forming centrosymmetric dimers and generating R(2) (2)(8)
      ring motifs.

PMID- 22590035
TI  - A triclinic polymorph of N-[4-(4-methyl-benzene-sulfonamido)-phenyl-sulfon
      yl]acetamide.
AB  - In the asymmetric unit of the title compound, C(15)H(16)N(2)O(5)S(2), there are
      two symmetry-independent mol-ecules which adopt similar conformations, with
      dihedral angles between the aromatic rings of 59.30 (8) and 61.81 (8) degrees ,
      and dihedral angles between acetamide group and the benzene ring of 77.08 (10)
      and 78.40 (10) degrees . Each type of mol-ecule forms similar one-dimensional
      polymeric structures extending along the b axis via N-H?O hydrogen bonds. These
      hydrogen bonds generate two types of centrosymmetric motifs, R(2) (2)(8) and R(2)
      (2)(20). Moreover C-H?O inter-actions assemble the mol-ecules into a three
      dimensional framework. The crystal structure was determined from a non-merohedral
      twin [ratio of the twin components = 0.322 (4):0.678 (4)].

PMID- 22590036
TI  - 1,2-Bis(4-methyl-benz-yl)diselane.
AB  - The title mol-ecule, C(16)H(18)Se(2), features a diselenide bridge between two 4
      methyl-benzyl units, in which the central C-Se-Se-C torsion angle is 88.1 (3)
      degrees , while the two Se-Se-C-C fragments assume gauche conformations, with
      torsion angles of -51.8 (5) and 59.1 (4) degrees . The dihedral angle between the
      benzene rings is 78.9 (2) degrees .

PMID- 22590037
TI  - Diisopropyl-ammonium nitrite.
AB  - In the title mol-ecular salt, C(6)H(16)N(+).NO(2) (-), the cation forms two N-H?O
      hydrogen bonds to nearby nitrite anions which link the ionic units into chains
      propagating along the b-axis direction.

PMID- 22590038
TI  - Ethyl 2-{3-[(6-chloro-pyridin-3-yl)meth-yl]-2-(nitro-imino)-imidazolidin-1
      yl}acetate.
AB  - In the title compound, C(13)H(16)ClN(5)O(4), the imidazole ring is in a slight
      envelope conformation. The dihedral angle between the pyridine ring and the four
      essentially planar atoms [maximum deviation 0.015 (2) A] of the imidazole ring is
      80.8 (1) degrees . In, the crystal, weak C-H?O and C-H?N hydrogen bonds are
      present. In addition, there are weak pi-pi stacking inter-actions between
      symmetry-related pyridine rings with a centroid-centroid distance of 3.807 (1) A.

PMID- 22590039
TI  - 4-Meth-oxy-N-(4-nitro-benz-yl)aniline.
AB  - In the title compound, C(14)H(14)N(2)O(3), the nitro group is nearly coplanar
      with the benzene ring to which it is bonded [dihedral angle = 1.70 (2) degrees ],
      and this ring is para-substituted by the amino-methyl-ene group. The dihedral
      angle between the benzene rings is 57.8 (1) degrees . The crystal structure is
      stabilized by N-H?O and C-H?O hydrogen bonds and weak C-H?pi inter-actions are
      also observed.

PMID- 22590040
TI  - A new polymorph of 5,5'-(ethane-1,2-di-yl)bis-(1H-tetra-zole).
AB  - The asymmetric unit of the title compound, C(4)H(6)N(8), contains a quarter of
      the mol-ecule, which possesses a crystallographically imposed centre of symmetry
      with all non-H atoms situated on a mirror plane. The crystal packing exhibits
      inter-molecular N-H?N hydrogen bonds and pi-pi stacking inter-actions between the
      tetra-zole rings of adjacent mol-ecules [centroid-centroid distance = 3.4402 (10)
      A].

PMID- 22590041
TI  - Bis-(guanidinium) naphthalene-1,5-di-sulfonate-18-crown-6 (1/1).
AB  - In the crystal of the title compound, 2CH(6)N(3) (+).C(10)H(6)O(6)S(2) (2
      ).C(12)H(24)O(6), the 1,5-naphthnalenedisulfonate anion and the 18-crown-6 mol
      ecule lie across inversion centers. The guanidin-ium cation links with the 1,5
      naphthnalenedisulfonate anion and 18-crown-6 mol-ecule via N-H?O hydrogen bonds.

PMID- 22590042
TI  - 2-Amino-3-chloro-5-nitro-benzamide.
AB  - The amide group in the title compound, C(7)H(6)ClN(3)O(3), is significantly
      twisted out of the plane of the benzene ring [C-C-C-O = 34.2 (5) degrees ]
      whereas the nitro group is almost co-planar [O-N-C-C = 4.0 (5) degrees ] with the
      ring. Intra-molecular N-H?O and N-H?Cl hydrogen bonds occur. In the crystal, the
      mol-ecules are linked by N-H?O hydrogen bonds, generating layers propagating in
      the ab plane.

PMID- 22590043
TI  - 4-[3,4-Dimethyl-1-(4-methyl-phen-yl)-5-oxo-4,5-dihydro-1H-pyrazol-4-yl]-3,4
      dimethyl-1-(4-methyl-phen-yl)-4,5-dihydro-1H-pyrazol-5-one.
AB  - In the title compound, C(24)H(26)N(4)O(2), the complete mol-ecule is generated by
      the application of twofold symmetry. The pyrazole ring is approximately planar
      [r.m.s. deviation = 0.026 A] and the benzene ring is twisted out of this plane
      [dihedral angle = 21.94 (7) degrees ]. A twist in the mol-ecule about the central
      C-C bond [1.566 (3) A] is also evident [C-C-C-C torsion angle = 44.30 (14)
      degrees ]. Supra-molecular layers in the bc plane are formed in the crystal
      packing via C-H?O and C-H?pi inter-actions.

PMID- 22590044
TI  - 4-{2-[4-(Dimethyl-amino)-phen-yl]ethen-yl}-1-methyl-pyridinium 4-nitro-benzene
      sulfonate.
AB  - The asymmetric unit of the title salt, C(16)H(19)N(2) (+). C(6)H(4)NO(5)S(-),
      consists of two cations and two anions. The crystal structure is stabilized by pi
      pi inter-actions between the pyridyl and phenyl rings of the cations, with a
      centroid-centroid distance of 3.7323 (6) A.

PMID- 22590045
TI  - Rubrene endoperoxide acetone monosolvate.
AB  - The title acetone solvate, C(42)H(28)O(2).C(3)H(6)O [systematic name: 1,3,10,12
      tetra-phenyl-19,20-dioxapenta-cyclo-[10.6.2.0(2,11).0(4,9).0(13,18)]icosa
      2(11),3,5,7,9,13,15,17-octa-ene acetone monosolvate], is a photooxygenation
      product of rubrene (systematic name: 5,6,11,12-tetra-phenyl-tetra-cene). The mol
      ecule bends at the bridgehead atoms, which are linked by the O-O transannular
      bond, with a dihedral angle of 49.21 (6) degrees  between the benzene ring and
      the naphthalene ring system of the tetra-cene unit. In the crystal, the rubrene
      mol-ecules are linked by C-H?O hydrogen bonds into a column along the c axis. The
      acetone solvent mol-ecules form a dimer around a crystallographic inversion
      centre through a carbon-yl-carbonyl dipolar inter-action. A C-H?O hydrogen bond
      between the rubrene and acetone mol-ecules is also observed.

PMID- 22590046
TI  - 6beta-Methyl-3,20-dioxopregn-4-en-17-yl acetate.
AB  - The title compound, C(24)H(34)O(4), is a precursor of Megestrol acetate. Ring A
      has a half-chair conformation [Q = 0.446 (3) A, theta = 54.6 (4) degrees  and phi
      = 9.5 (4) degrees ]. Ring D adopts a 13beta-envelope conformation [Q = 0.463 (2)
      A and phi = 188.2 (3) degrees ].

PMID- 22590047
TI  - Marbofloxacin.
AB  - IN THE TITLE COMPOUND, [SYSTEMATIC NAME: 9-fluoro-2,3-dihydro-3-methyl-10-(4
      methyl-piperazin-1-yl)-7-oxo-7H-pyrido[1,2,3-ij][1,2,4]benzoxadiazine-6-carb-oxy
      lic acid], C(17)H(19)FN(4)O(4), the carbonyl and carboxyl groups are coplanar
      with the quinoline ring, making a dihedral angle of 2.39 (2) degrees . The
      piperazine ring adopts a chair conformation and the oxadiazinane ring displays an
      envelope conformation with the CH(2) group at the flap displaced by 0.650 (2) A
      from the plane through the other five atoms. The mol-ecular structure exhibits an
      S(6) ring motif, owing to an intra-molecular O-H?O hydrogen bond. In the crystal,
      weak C-H?F hydrogen bonds link mol-ecules into layers parallel to the ab plane.

PMID- 22590049
TI  - The aluminoarsenate K(1.8)Sr(0.6)Al(3)(AsO(4))(4).
AB  - The title compound, potassium strontium trialuminium tetra-arsenate, was prepared
      by solid-state reaction. The structure consists of AlO(6) octa-hedra (site
      symmetries 2.. and 2/m) and two AsO(4) tetra-hedra (.2. and m..) sharing corners
      and edges to form a two-dimensional structure parallel to (010). The cations are
      occupationally disordered and are located in the interlayer space. For both types
      of cations, distorted coordination polyhedra are observed.

PMID- 22590050
TI  - Dicobalt(II) lead(II) hydrogenphos-phate(V) phos-phate(V) hydroxide monohydrate.
AB  - The title compound, Co(2)Pb(HPO(4))(PO(4))OH.H(2)O, which was synthesized under
      hydro-thermal conditions, crystallizes in a new structure type. Except for two O
      atoms in general positions and two Co atoms on centres of symmetry, all other
      atoms in the asymmetric unit (1 Pb, 2 Co, 2 P, 8 O and 4 H) are located on mirror
      planes. The structure is built up from two infinite linear chains, viz.(1)
      (infinity)[CoO(2/1)(H(2)O)(2/2)O(2/2)] and (1)
      (infinity)[CoO(2/1)(OH)(2/2)O(2/2)], of edge-sharing CoO(6) octa-hedra running
      along [010]. Adjacent chains are linked to each other through PO(4) and PO(3)(OH)
      tetra-hedra, leading to the formation of layers parallel to (100). The three
      dimensional framework is formed by stacking along [100] of adjacent layers that
      are held together by distorted PbO(8) polyhedra. Hydrogen bonds of the type O-H?O
      involving the water mol-ecule are very strong, while those O atoms involving the
      OH groups form weak bifurcated and trifurcated hydrogen bonds.

PMID- 22590051
TI  - Dipotassium tris-odium triphosphate, K(2)Na(3)P(3)O(10).
AB  - The structure of the title compound, K(2)Na(3)P(3)O(10), is characterized by open
      chains of three PO(4) tetra-hedra linked by single oxygen bridges. The P(3)O(10)
      groups have crystallographic twofold symmetry, with the central P atom being
      located on the twofold rotation axis. One of the sodium ions lies on a centre of
      inversion, whereas all the remaining atoms are in general positions. The
      structure is isotypic with that of the high-temperature form of Na(5)P(3)O(10)
      phase I.

PMID- 22590052
TI  - Distrontium lithium beryllium triborate, Sr(2)LiBeB(3)O(8).
AB  - Single crystals of distrontium lithium beryllium triborate, Sr(2)LiBeB(3)O(8),
      were obtained by spontaneous nucleation from a high-temperature melt. In the
      Sr(2)Li[BeB(3)O(8)] structure, [BeB(2)O(7)](6-) rings, made up from one BeO(4)
      tetra-hedron and two BO(3) triangles, are connected to each other by [BO(3)]
      triangles to form the smallest repeat unit {[BeB(3)O(8)](8-)} and then form
      chains along the b axis. The Sr(2+) cations are seven- or eight--coordinated and
      Li(+) cations are tetra--coordinated and lie between the chains.

PMID- 22590053
TI  - Redetermination of Ce[B(5)O(8)(OH)(H(2)O)]NO(3).2H(2)O.
AB  - The crystal structure of Ce[B(5)O(8)(OH)(H(2)O)]NO(3).2H(2)O, cerium(III) aqua
      hydroxidoocta-oxidopenta-borate nitrate dihydrate, has been redetermined from
      single-crystal X-ray diffraction data. In contrast to the previous determination
      [Li et al. (2003 ?). Chem. Mater.15, 2253-2260], the present study reveals the
      location of all H atoms, slightly different fundamental building blocks (FBBs) of
      the polyborate anions, more reasonable displacement ellipsoids for all non-H
      atoms, as well as a model without disorder of the nitrate anion. The crystal
      structure is built from corrugated polyborate layers parallel to (010). These
      layers, consisting of [B(5)O(8)(OH)(H(2)O)](2-) anions as FBBs, stack along [010]
      and are linked by Ce(3+) ions, which exhibit a distorted CeO(10) coordination
      sphere. The layers are additionally stabilized via O-H?O hydrogen bonds between
      water mol-ecules and nitrate anions, located at the inter-layer space. The
      [BO(3)(H(2)O)]-group shows a [3 + 1] coordination and is considerably distorted
      from a tetra-hedral configuration. Bond-valence-sum calculation shows that the
      valence sum of boron is only 2.63 valence units (v.u.) when the contribution of
      the water mol-ecule (0.49 v.u.) is neglected.

PMID- 22590054
TI  - Garnet-type Mn(3)Cr(2)(GeO(4))(3).
AB  - Single crystals of garnet-type trimanganese(II) dichrom-i-um(III) tris
      [orthogermanate(IV)], Mn(II) (3)Cr(III) (2)(GeO(4))(3), were obtained by
      utilizing a chemical transport reaction. Corres-ponding to the mineral garnet
      with the general formula A(II) (3)B(III) (2)(SiO(4))(3), each of the four
      elements occupies only one crystallographically distinct position. Mn(2+)
      occupies the respective A position (Wyckoff site 24c, site symmetry 2.22), being
      surrounded by eight O atoms that form a distorted cube [d(Mn-O) = 2.291 (2) and
      2.422 (2) A, 4* each], while Cr(3+) on the B position (Wyckoff site 16a, site
      symmetry .-3.) is situated in a slightly distorted octa-hedron of six O(2-)
      anions [d(Cr-O) = 1.972 (2) A, 6*]. In addition, the O atoms on general site 96h
      form isolated [GeO(4)](4-) tetra-hedra with Ge(4+) on site 24d [site symmetry 
      4..; d(Ge-O) = 1.744 (2) A, 4*].

PMID- 22590055
TI  - Trisodium scandium bis-(orthoborate).
AB  - Single crystals of tris-odium scandium bis-(orthoborate), Na(3)Sc(BO(3))(2), have
      been obtained by spontaneous crystallization from an Na(2)O-Sc(2)O(3)-B(2)O(3)
      melt. The crystal structure features a three-dimensional framework composed of
      planar [BO(3)](3-) groups and distorted ScO(6) octa-hedra with Na atoms in the
      cavities. The Sc atom occupies a special position (Wyckoff position 2b, site
      symmetry -1) and of the two Na atoms, one occupies a special position (Wyckoff
      position 2c, site symmetry -1).

PMID- 22590056
TI  - Tetra-aqua-tetra-manganese(II) catena-[germanodihydroxidodi(hydrogen
      phosphate)diphosphate].
AB  - The title compound, Mn(4)(H(2)O)(4)[Ge(OH)(2)(HPO(4))(2)(PO(4))(2)], was
      synthesized by the solvothermal method. Its crystal structure is isotypic with
      the iron and cobalt analogues [Huang et al. (2012 ?). Inorg. Chem.51, 3316-3323].
      In the crystal structure, the framework is built from undulating manganese
      phosphate sheets parallel to (010) inter-connected by GeO(6) octa-hedra (at the
      inversion center), resulting in a three-dimensional network with eight-membered
      ring channels into which all the protons point. The undulating manganese
      phosphate sheet consists of zigzag manganese octa-hedral chains along [10-1],
      built from MnO(4)(OH)(OH(2)) octa-hedra and MnO(5)(OH(2)) octa-hedra by sharing
      their trans or skew edges, which are inter-connected by PO(3)(OH) and PO(4) tetra
      hedra via corner-sharing. The crystal structure features extensive O-H?O hydrogen
      bonding inter-actions.

PMID- 22590057
TI  - Poly[[diaqua-hexa-MU-cyanido-cerium(III)ferrate(III)] dihydrate].
AB  - In the structure of the title complex, {[CeFe(CN)(6)(H(2)O)(2)].2H(2)O}(n), the
      Ce(III) and Fe(III) atoms exhibit square anti-prismatic [CeN(6)(H(2)O)(2)] (site
      symmetry m2m) and octahedral [FeC(6)] (site symmetry 2/m) coordination
      geometries, respectively. The metal atoms are linked alternately through the
      cyanide groups, forming a three-dimensional framework in which the
      {Ce(2)Fe(2)(CN)(4)} puckered square unit is the basic building block. The crystal
      packing is enforced by O-H?O and O-H?N hydrogen bonds, including the
      uncoordinated water molecule which is located on a mirror plane.

PMID- 22590058
TI  - Poly[[diaqua-[MU(2)-3-carb-oxy-5-(pyridine-4-carboxamido)-benzoato][MU(4)-5
      (pyridine-4-carboxamido)-isophthalato]cerium(III)] monohydrate].
AB  - In the title compound,
      {[Ce(C(14)H(9)N(2)O(5))(C(14)H(8)N(2)O(5))(H(2)O)(2)].H(2)O}(n), three carboxyl
      groups of two independent isophthalate anions are deprotonated and they bridge
      the Ce(III) cations, forming a two-dimensional polymeric structure parallel to
      (001); another carboxyl group is not deprotonated and links with the adjacent
      pyridine ring via an O-H?N hydrogen bond. The Ce(III) cation is coordinated by
      six O atoms from carboxyl groups and two O atoms from coordinated water mol
      ecules in a distorted square-anti-prismatic arrangement. Extensive O-H?O and O
      H?N hydrogen bonding occurs in the crystal structure.

PMID- 22590059
TI  - Tris(1,10-phenanthroline-kappa(2)N,N')iron(II) bis-[(1,10-phenanthroline
      kappa(2)N,N')tetra-kis-(thio-cyanato-kappaN)chromate(III)] acetonitrile tris
      olvate monohydrate.
AB  - Single crystals of the title heterometallic compound,
      [Fe(C(12)H(8)N(2))(3)][Cr(NCS)(4)(C(12)H(8)N(2))](2).3CH(3)CN.H(2)O or
      [Fe(Cphen)(3)][Cr(NCS)(4)(phen)](2).3CH(3)CN.H(2)O, were pre-pared using the one
      pot open-air reaction of iron powder, Reineckes salt and 1,10-phenanthroline
      (phen) in acetonitrile. The asymetric unit consists of an [Fe(phen)(3)](2+)
      cation, two [Cr(phen)(NCS)(4)](-) anions, three acetonitrile solvent mol-ecules
      and a water mol-ecule. The Fe and Cr atoms both show a slightly distorted octa
      hedral FeN(6) and CrN(6) coordination geometry with adjacent angles in the range
      79.67 (12)-95.21 (12) degrees . No classical hydrogen bonding involving the water
      molecule is observed.

PMID- 22590060
TI  - Diaqua-bis-(1-methyl-1H-imidazole-kappaN(3))bis-[2-(naphthalen-1-yl)acetato
      kappaO]cobalt(II).
AB  - In the title compound, [Co(C(12)H(9)O(2))(2)(C(4)H(6)N(2))(2)(H(2)O)(2)], the
      Co(II) ion is located on an inversion centre and displays a distorted octa-hedral
      coordination geometry. Two O atoms from two water mol-ecules and two carboxyl-ate
      O atoms from two 2-(naphthalen-1-yl)acetate ligands are in the equatorial plane
      and two N atoms from two 1-methyl-1H-imidazole ligands are in the axial
      positions. The structure is stabilized by intra-molecular O-H?O hydrogen bonds.
      Inter-molecular O-H?O hydrogen bonds link the complex mol-ecules into chains
      along [100].

PMID- 22590061
TI  - {S-Benzyl 3-[(6-methyl-pyridin-2-yl-kappaN)methyl-idene]dithio-carbazato
      kappa(2)N(3),S}zinc.
AB  - The title compound, [Zn(C(15)H(14)N(3)S(2))(2)], contains two chemically
      equivalent Schiff base anions that are coordinated to the Zn(II) ion as
      tridentate N,N',S-chelating ligands, creating a distorted octa-hedral environment
      [the smallest angle being 75.40 (6) degrees  and the widest angle being 162.87
      (6) degrees ], with the two S atoms in cis positions. The dihedral angle between
      the mean planes of the two coordinating ligands is 85.65 (5) degrees . Weak C-H?S
      hydrogen bonds are also observed.

PMID- 22590062
TI  - trans-Dichloridobis(quinoline-kappaN)platinum(II).
AB  - In the title complex, trans-[PtCl(2)(C(9)H(7)N)(2)], the Pt(II) ion is four
      coordinated in an essentially square-planar coordination environment defined by
      two N atoms from two quinoline (qu) ligands and two Cl(-) anions. The Pt atom is
      located on an inversion centre and thus the asymmetric unit contains one half of
      the complex; the PtN(2)Cl(2) unit is exactly planar. The dihedral angle between
      the PtN(2)Cl(2) unit and the quinoline ligand is 85.1 (1) degrees . In the
      crystal, the complex mol-ecules are stacked into columns along the b axis. In the
      columns, several inter-molecular pi-pi inter-actions between the six-membered
      rings are present, the shortest ring centroid-centroid distance being 3.733 (5) A
      between pyridine rings.

PMID- 22590063
TI  - Poly[aqua(MU(3)-5-aza-niumylisophthalato)-(MU-oxalato)neodymium(III)].
AB  - The title compound, [Nd(C(8)H(6)NO(4))(C(2)O(4))(H(2)O)](n), is a layer-like
      coordination polymer. The Nd(III) ion is coordinated by four carboxyl-ate O atoms
      from three bridging 5-aza-nium-yl-isophthalate (Haip) ligands, four carboxyl-ate
      O atoms from two oxalate (ox) anions and one ligated water mol-ecule in a
      tricapped trigonal-prismatic geometry. The Haip anion acts as a MU(3)-bridge,
      connecting three Nd(III) ions through two carboxyl-ate groups; the ox anion
      adopts a bis-bidentate-bridging mode, linking two Nd(III) ions. The layer
      framework is further extended to a three-dimensional supra-molecular structure
      through N-H?O and O-H?O hydrogen bonds.

PMID- 22590064
TI  - Bis[2-(2-oxoindolin-3-yl-idene)-N-phenylhydrazinecarbothio-amidato
      kappa(3)O,N(2),S]nickel(II) dimethyl-formamide monosolvate.
AB  - The asymmetric unit of the title compound, [Ni(C(15)H(11)N(4)OS)(2)].C(3)H(7)NO,
      contains one Ni(II) complex mol-ecule and one disordered dimethyl-formamide
      solvent mol-ecule. The Ni(II) ion is six-coordinated in a distorted octa-hedral
      geometry by two N, two O and two S atoms. An intra-molecular C-H?S hydrogen bond
      generates an S(6) ring motif. In the crystal, mol-ecules are linked through inter
      molecular N-H?S, N-H?O, C-H?N, C-H?O and C-H?S hydrogen bonds into infinite two
      dimensional network parallel to the ab plane. The structure is further stablized
      by weak C-H?pi inter-actions. The dimethylformamide solvent molecule is
      disordered over two sets of sites in a 0.514 (15):0.486 (15) ratio.

PMID- 22590065
TI  - Chlorido[4-chloro-2-(pyridin-2-yl-methyl-imino-meth-yl)phenolato
      kappa(3)N,N',O]copper(II).
AB  - In the title complex, [Cu(C(13)H(10)ClN(2)O)Cl], the Cu(II) ion is coordinated by
      one O atom and two N atoms of the tridentate Schiff base ligand and one chloride
      ion, forming a slightly distorted square-planar geometry. Weak Cu?Cl inter
      actions [2.793 (5) A] result in the formation of a chain along the a axis.

PMID- 22590066
TI  - Poly[[tri-MU(3)-hydroxido-tris-(MU(4)-pyridine-2,5-dicarboxyl
      ato)trineodymium(III)] monohydrate].
AB  - In the title compound, {[Nd(3)(C(7)H(3)NO(4))(3)(OH)(3)].H(2)O}(n), the Nd(III)
      atom is eight-coordinated by the three O atoms of three asymmetrically MU(3)
      bridging hydroxide groups, by four carboxyl-ate O atoms of four different
      pyridine-2,5-dicarboxyl-ate (2,5-pydc) ligands, and by the N atom of a 2,5-pydc
      ligand. Six Nd atoms are connected by six hydroxide groups, forming an
      [Nd(6)(MU(3)-OH)(6)] cluster unit of symmetry -3 and a slightly compressed octa
      hedral geometry. Adjacent [Nd(6)(MU(3)-OH)(6)] clusters are connected by the 2,5
      pydc ligands, via O and N atoms, forming chains along the c axis. The remaining O
      atoms of the 2,5-pydc ligands link these chains into a three-dimensional
      framework. A disordered water molecule, located on a threefold rotation axis at
      the opposite side of the [Nd(6)(MU(3)-OH)(6)] cluster and exposed to each of the
      three Nd atoms, completes the structure.

PMID- 22590067
TI  - catena-Poly[[[aqua-[3-(3-hy-droxy-phen-yl)prop-2-enoato]samarium(III)]-bis-[MU(2)
      3-(3-hy-droxy-phen-yl)prop-2-enoato]] monohydrate].
AB  - The title Sm(III) compound, {[Sm(C(9)H(7)O(3))(3)(H(2)O)].H(2)O}(n), was obtained
      under hydrothermal conditions. Its structure is isotypic with the analogous Eu
      complex. The latter was reported incorrectly in space group P1 by Yan et al. [J.
      Mol. Struct. (2008), 891, 298-304]. This was corrected by Marsh [Acta Cryst. B65,
      782-783] to P-1. The Sm(III) ion is nine-coordinated by O atoms from one
      coordinating water molecule and the remaining ones from the 3-(3-hy-droxy-phen
      yl)prop-2-enoatate anions (one bidentate, two bidentate and bridging, two
      monodentate bridging), leading to a distorted tricapped trigonal-prismatic
      coordination polyhedron surrounded by solvent water mol-ecules. In the crystal,
      extensive intermolecular O-H?O hydrogen-bonding inter-actions and pi-pi inter
      actions [centroid-centroid separation = 3.9393 (1) A] lead to the formation of a
      three-dimensional supra-molecular network.

PMID- 22590068
TI  - trans-Carbonyl-chloridobis[diphen-yl(4-vinyl-phen-yl)phosphane-kappaP]rhodium(I).
AB  - In the title compound, trans-[RhCl(C(20)H(17)P)(2)(CO)], the Rh(I) atom is
      situated on a center of symmetry, resulting in a statistical 1:1 disorder of the
      chloride [Rh-Cl = 2.383 (2) A] and carbonyl [Rh-C = 1.752 (7) A] ligands. The
      distorted trans square-planar environment is completed by two P atoms [Rh-P =
      2.3251 (4) A] from two diphen-yl(4-vinyl-phen-yl)phosphane ligands. The vinyl
      group is disordered over two sets of sites in a 0.668 (10):0.332 (10) ratio. The
      crystal packing exhibits weak C-H?Cl and C-H?O hydrogen bonds and pi-pi inter
      actions between the phenyl rings of neighbouring mol-ecules, with a centroid
      centroid distance of 3.682 (2) A.

PMID- 22590069
TI  - Dichloridobis(pyrazine-2-carboxamide-kappaN(4))zinc(II).
AB  - In the crystal of the title compound, [ZnCl(2)(C(5)H(5)N(3)O)(2)], the mol-ecule
      has m symmetry, with the Zn(II) cation and Cl(-) anions located on the mirror
      plane. The Zn(II) cation is coordinated by two Cl(-) anions and two pyrazine-2
      carboxamide ligands in a distorted ZnCl(2)N(2) tetra-hedral geometry. The two
      pyrazine rings are nearly perpendicular to each other [dihedral angle = 86.61
      (10) degrees ]. Inter-molecular N-H?O and N-H?N hydrogen bonds and weak C-H?O
      inter-actions stabilize the crystal packing.

PMID- 22590070
TI  - cis-Tetra-chloridobis(1H-imidazole-kappaN(3))platinum(IV).
AB  - In the title complex, cis-[PtCl(4)(C(3)H(4)N(2))(2)], the Pt(IV) ion lies on a
      twofold rotation axis and is coordinated in a slightly distorted octa-hedral
      geometry. The dihedral angle between the imidazole rings is 69.9 (2) degrees . In
      the crystal, mol-ecules are linked by N-H?Cl hydrogen bonds, forming a three
      dimensional network.

PMID- 22590071
TI  - (Methanol-kappaO){1-[2-(piperazin-4-ium-1-yl-kappaN(1))ethyl-imino-methyl
      kappaN]naphthalen-2-olato-kappaO}bis-(thio-cyanato-kappaN)nickel(II) methanol
      monosolvate.
AB  - In the title solvated complex, [Ni(C(17)H(21)N(3)O)(NCS)(2)(CH(3)OH)].CH(3)OH,
      the Ni(2+) ion is coordinated by one phenolate O, one imine N, and one amine N
      atom of the tridentate Schiff base ligand, two thio-cyanate N atoms and one
      methanol O atom, resulting in a distorted cis-NiO(2)N(4) octa-hedral geometry.
      The chelate ring formed by the phenolate O and imine N atoms approximates to an
      envelope with the Ni atom as the flap, whereas the chelate ring formed by the two
      N atoms is twisted about the C-C bond. In the crystal, the components are linked
      by O-H?O, N-H?O, N-H?S, and O-H?S hydrogen bonds.

PMID- 22590072
TI  - Tris-(nitrato-kappa(2)O,O')bis[4,4,5,5-tetra-methyl-2-(pyridin-2-yl
      kappaN)imidazoline-1-oxyl 3-oxide-kappaO]holmium(III).
AB  - In the title compound, [Ho(NO(3))(3)(C(12)H(16)N(3)O(2))(2)], the Ho(III) ion is
      ten-coordinated in a distorted bicapped square-anti-prismatic environment by two
      N,O-bidentate nitronyl nitroxide radical ligands and three O,O'-bidentate nitrate
      anions. Complex mol-ecules are connected by C-H?O hydrogen bonds into a three
      dimensional network.

PMID- 22590073
TI  - Potassium [1-(tert-but-oxy-carbon-yl)-1H-indol-3-yl]trifluoro-borate hemihydrate.
AB  - The asymmetric unit of the title salt, K(+).C(13)H(14)BF(3)NO(2).0.5H(2)O,
      consists of two derivatized indolyltrifluoridoborate anions, two potassium
      cations and one water mol-ecule. Within the indolyltrifluoro-borate anions, the
      least-square planes consisting of the carboxyl group and the adjacent quarternary
      C atom of the tert-butyl groups deviate significantly from coplanarity with the
      indolyl planes [20.44 (11) and 21.02 (10) degrees ]. The potassium ions are
      coordinated by six atoms (one K(+) ion by two O and four F atoms, and the second
      K(+) ion by one O and five F atoms), however, one of the potassium ions undergoes
      an additional weak potassium-pi inter-action (K?centroid = 3.722 A). The packing
      is stabilized by sequential O-H?O hydrogen bonds along [100] between water mol
      ecules and also by O-H?F hydrogen bonds.

PMID- 22590074
TI  - Bis{2-amino-2-oxo-N-[(1E)-1-(pyridin-2-yl-kappaN)ethyl-idene]acetohydrazidato
      kappa(2)N',O(1)}nickel(II).
AB  - In the title compound, [Ni(C(9)H(9)N(4)O(2))(2)], the Ni(II) ion is situated on a
      twofold rotation axis and is coordinated by two O and four N atoms from two
      tridentate {2-amino-2-oxo-N-[(1E)-1-(pyridin-2-yl-kappaN)ethyl
      idene]acetohydrazidate ligands in a distorted octa-hedral geometry. In the
      crystal, N-H?O and N-H?N hydrogen bonds link the mol-ecules into columns in
      [001]. The porous crystal packing is further stabilized via pi-pi inter-actions
      between the pyridine rings of neighbouring mol-ecules [centroid-centroid distance
      = 3.746 (3) A] with voids of 270 A(3).

PMID- 22590075
TI  - Bis(acetato-kappaO)bis-(pyridine-2-aldoxime-kappa(2)N,N')nickel(II).
AB  - In the mononuclear title compound, [Ni(CH(3)COO)(2)(C(6)H(6)N(2)O)(2)], the
      Ni(II) atom is coordinated by two pyridine-2-aldoxime (PaoH) ligands and two
      acetate groups, with cis coordination for the pairs of identical ligands. While
      each acetate group binds to the Ni(II) atom by one O atom, each PaoH chelates the
      Ni(II) atom through two N atoms. The O atom on PaoH is not deprotonated and does
      not participate in bonding to the Ni(II) atom. Thus, the Ni(II) atom exhibits an
      octa-hedral environment. Intra-molecular O-H?O hydrogen-bonding inter-actions and
      inter-molecular C-H?O hydrogen-bonding inter-actions are present in the
      structure. Adjacent mol-ecules pack along [100] through van der Waals forces.

PMID- 22590076
TI  - Bis[5-chloro-2-(phenyl-diazenyl-kappaN(2))pyridine-kappaN]bis-(thio-cyanato
      kappaN)iron(II).
AB  - In the title complex, [Fe(NCS)(2)(C(11)H(8)ClN(3))(2)], the Fe(II) atom is
      coordinated by two N atoms from the thio-cyanate ligands and four N atoms from
      two chelating 5-chloro-2-(phenyl-diazen-yl)pyridine ligands, generating a fairly
      regular FeN(6) octa-hedral coordination geometry. The thio-cyanate ions are in a
      cis disposition and the pyridine N atoms are in a trans orientation. In the
      crystal, a short inter-molecular Cl?S contact [3.366 (3) A] is observed.

PMID- 22590078
TI  - Aqua-[1-(1,10-phenanthrolin-2-yl-kappa(2)N,N')-1H-pyrazol-3-amine
      kappaN(2)](sulfato-kappaO)copper(II) methanol monosolvate dihydrate.
AB  - In the title compound, [Cu(SO(4))(C(15)H(11)N(5))(H(2)O)].CH(3)OH.2H(2)O, the
      Cu(II) ion is in a distorted square-pyramidal geometry, in which three N atoms
      from the chelating 1-(1,10-phenanthrolin-2-yl)-1H-pyrazol-3-amine ligand and one
      O atom from a sulfate anion define the basal plane and the O atom from the
      coordinating water mol-ecule is located at the apex. In the crystal, hydrogen
      bonding inter-actions involving the coordinating and solvent water mol-ecules,
      the methanol solvent mol-ecule and the amine group (one with an intra-molecular
      inter-action to one of the sulfate O atoms) of the complex are observed. pi-pi
      inter-actions between symmetry-related phenantroline moieties, with a shortest
      centroid-centroid inter-action of 3.573 (2) degrees , are also present.

PMID- 22590077
TI  - (MU-4-Bromo-3,5-dimethyl-pyrazolato-kappa(2)N(1):N(2))-MU-chlorido-bis-[bis(4
      bromo-3,5-dimethyl-pyrazole-kappaN(2))chloridocopper(II)] acetonitrile
      monosolvate.
AB  - In the title dinuclear complex,
      [Cu(2)(C(5)H(6)BrN(2))Cl(3)(C(5)H(7)BrN(2))(4)].CH(3)CN, both Cu(II) ions are in
      slightly distorted square-pyramidal coordination geometries. The basal planes are
      defined by three N atoms from three 4-bromo-3,5-dimethyl-pyrazolate ligands, one
      of which is bridging, and one Cl ligand. A bridging Cl ligand forms the apical
      site for both Cu(II) ions. In the crystal, N-H?Cl hydrogen bonds connect complex
      mol-ecules into chains along [100]. Intra-molecular N-H?Cl hydrogen bonds are
      also observed.

PMID- 22590079
TI  - [1,1'-Bis(diphenyl-phosphan-yl)ferrocene-kappa(2)P,P'](eta(5)-cyclo-penta-dien
      yl)(dicyanamido-kappaN)ruthenium(II) dichloro-methane monosolvate.
AB  - The title compound, [FeRu(C(5)H(5))(C(2)N(3))(C(17)H(14)P)(2)], was obtained by
      reaction of Cp(dppf)RuCl [dppf = 1,1'-bis-(diphenyl-phosphan-yl)ferrocene] with
      sodium dicyanamide in dichloro-methane. The Ru(II) atom is capped by an eta(5)
      cyclo-penta-dienyl (Cp) ring, a chelating dppf and a terminal C(2)N(3) unit,
      giving three-legged piano-stool geometry. The C-N-C angle of the N(CN)(2) ligand
      [120.8 (6) degrees ] is significantly smaller than that in the corresponding
      diruthenium complex [127.2 (9) degrees ; Zhang et al. (2003 ?). Inorg. Chem.42,
      633-640] due to steric hindrance between the two {Cp(PPh(3))(2)Ru} building
      blocks. Disorder was found in the dichloro-methane solvent mol-ecule, which was
      refined as disordered over two positions, with a site-occupancy ratio of
      0.53:0.47 (2).

PMID- 22590080
TI  - 5,6-Dihydro-1,10-phenanthroline-1,10-diium MU-oxido-bis-[penta
      fluoridotantalate(V)].
AB  - In the title compound, (C(12)H(12)N(2))[Ta(2)F(10)O], the doubly protonated 5,6
      dihydro-1,10-phenantroline-1,10-diium cation is located on a twofold rotation
      axis, whereas the isolated [Ta(2)OF(10)](2-) dianion has -1 symmetry. In the so
      far unknown dianion, the symmetry-related Ta(V) atoms are octa-hedrally
      coordinated by five F atoms and a bridging O atom, the latter being located on an
      inversion centre. The two pyridine rings in the cation make a dihedral angle of
      22.8 (4) degrees . The cations and dianions are arranged in layers parallel to
      (100) and are connected through N-H?F and C-H?F hydrogen-bonding inter-actions
      into a three-dimensional structure.

PMID- 22590081
TI  - Tetra-aqua-bis-[3-(pyridin-4-yl)benzoato-kappaN]manganese(II).
AB  - In the title compound, [Mn(C(12)H(8)NO(2))(2)(H(2)O)(4)], the Mn(2+) ion lies on
      a twofold rotation axis and has a distorted N(2)O(4) octa-hedral coordination
      geometry formed by four water O atoms in the equatorial plane and two apical
      pyridyl N atoms. A three-dimensional network is formed in the crystal structure
      by multiple O-H?O hydrogen bonds between the coordin-ating water molecules and
      the free carboxylate groups.

PMID- 22590082
TI  - cis-[1,4-Bis(diphenyl-phosphan-yl)butane-kappa(2)P,P']dichlorido(cyclo-hexane-1,2
      diamine-kappa(2)N,N')ruthenium(II) dichloro-methane monosolvate.
AB  - In the title compound, [RuCl(2)(C(6)H(14)N(2))(C(28)H(28)P(2))].CH(2)Cl(2), the
      Ru(II) ion is coordinated in a slightly distorted octa-hedral environment, formed
      by two cis-oriented chloride ligands, two cis P atoms of a 1,4-bis-(diphenyl
      phosphan-yl)butane ligand and two cis-chelating N atoms of a bidentate cyclo
      hexane-1,2-diamine ligand. In the crystal, pairs of mol-ecules form inversion
      dimers via N-H?Cl hydrogen bonds. In addition, intra-molecular N-H?Cl and weak C
      H?Cl, C-H?N, N-H?pi and C-H?pi hydrogen bonds are observed. One of the Cl atoms
      of the solvent mol-ecule is disordered over two sites with refined occupancies of
      0.62 (1) and 0.38 (1).

PMID- 22590083
TI  - catena-Poly[copper(I)-di-MU-bromido-copper(I)-bis-[MU-4-methyl-1H-1,2,4-triazole
      5(4H)-thione-kappa(2)S:S]].
AB  - In the title coordination polymer, [CuBr(C(3)H(5)N(3)S)](n), the Cu(I) atom
      adopts a tetra-hdral CuS(2)Br(2) coordination geometry arising from two S-bonded
      4-methyl-1H-1,2,4-triazole-3(4H)-thione ligands and two bromide ions. Both the S
      and Br atoms act as bridging ligands, connecting pairs of Cu(I) atoms and
      generating chains propagating in [100]. Inter-chain N-H?N hydrogen bonds generate
      layers in the ac plane. Weak intra-chain N-H?Br inter-actions also occur.

PMID- 22590084
TI  - trans-Bis(acetato-kappaO)bis-(2-amino-ethanol-kappa(2)N,O)nickel(II).
AB  - In the title compound, [Ni(CH(3)CO(2))(2)(C(2)H(7)NO)(2)], the Ni(II) cation,
      located on an inversion center, is N,O-chelated by two 2-amino-ethanol mol-ecules
      and further coordinated by two monodendate acetate anions in a slightly distorted
      octa-hedral geometry. The latter is stabilized by intra-molecular O-H?O hydrogen
      bonds involving the non-coordinated O atom of the acetate and the H atom of the
      hy-droxy group of the 2-amino-ethanol ligand. In the crystal, N-H?O hydrogen
      bonds link the mol-ecules into a three-dimensional supra-molecular framework that
      involves (a) the coordinated acetate O atom and one of the H atoms of the amino
      group and (b) the non-coordinated acetate O atom and the other H atom of the
      amino group.

PMID- 22590085
TI  - Bis(2,2'-bipyridyl-kappa(2)N,N')bis-(dicyanamido-kappaN)manganese(II).
AB  - In title complex, [Mn(C(2)N(3))(2)(C(10)H(8)N(2))(2)], the Mn(II) ion is
      coordinated in a slightly distorted octa-hedral geometry by six N atoms. Four of
      the N atoms are from two chelating bipyridine ligands and two are from a pair of
      cis-coordinated dicyanamide ligands. The dihedral angle formed by the mean planes
      of the bipyridine rings is 85.93 (14) degrees . The central N atom of one of the
      dicyanamide ligands was refined as disordered over two sites with equal
      occupancies.

PMID- 22590086
TI  - Tetra-kis[MU(3)-4-nitro-N-(5-phenyl-1,3,4-oxadiazol-2-yl)benzamidato]tetra-kis
      [methano-lsodium(I)].
AB  - In the title compound, [Na(4)(C(15)H(9)N(4)O(4))(4)(CH(3)OH)(4)], the N(3)O(3)
      environment around the Na(+) ion is distorted octa-hedral. In the unit cell, four
      Na(+) ions are bridged by four Schiff base anions, leading to a tetra-nuclear
      complex with -4 symmetry. O-H?N hydrogen bonds between the methanol mol-ecule and
      the Schiff base anion stabilize the structural set-up.

PMID- 22590087
TI  - Dichlorido[2-(3,5-dimethyl-1H-pyrazol-1-yl-kappaN(2))quinoline-kappaN]zinc.
AB  - The Zn(II) atom in the title compound, [ZnCl(2)(C(14)H(13)N(3))], is coordinated
      by a Cl(2)N(2) donor set defined by quinoline and pyrazole N atoms of the
      chelating ligand and two Cl atoms. Distortions from the ideal tetra-hedral
      geometry relate to the restricted bite angle of the chelating ligand [N-Zn-N =
      78.54 (12) degrees ]. In the crystal, mol-ecules are connected into a three
      dimensional structure by C-H?Cl inter-actions, involving both Cl atoms, and pi-pi
      inter-actions that occur between the pyrazole ring and each of the pyridine and
      benzene rings of the quinoline residue [inter-centroid distances = 3.655 (2) and
      3.676 (2) A].

PMID- 22590088
TI  - Bis[2-(benzyl-imino-meth-yl)pyrrol-1-ido-kappa(2)N,N']bis-(dimethyl-amido
      kappaN)titanium(IV).
AB  - The mononuclear title complex, [Ti(C(2)H(6)N)(2)(C(12)H(11)N(2))(2)], was
      synthesized by the reaction of 1-phenyl-N-[(pyrrol-2-yl)methyl-idene]methanamine
      with Ti(NMe(2))(4). The Ti(IV) atom is coordinated in a distorted octa-hedral
      geometry by four N atoms from two derivatized methanamine ligands and two N atoms
      from two dimethyl-amide ions. The dihedral angles between the pyrrole and phenyl
      rings in the bidentate ligands are 62.36 (9) and 78.32 (8) degrees . In the
      crystal, a weak pi-pi stacking inter-action [centroid-centroid distance = 3.864
      (2) A] involving centrosymmetrically related mol-ecules is observed.

PMID- 22590089
TI  - catena-Poly[[[aqua-(4,4'-dimethyl-2,2'-bipyridine-kappa(2)N,N')zinc]-MU-3-chloro
      benzene-1,2-dicaboxylato-kappa(2)O(2):O(3)] [[(4,4'-dimethyl-2,2'-bipyridine
      kappa(2)N,N')zinc]-MU-3-chloro-benzene-1,2-dicaboxylato-kappa(2)O(2):O(3)]].
AB  - In the title compound,
      {[Zn(C(8)H(3)ClO(4))(C(12)H(12)N(2))(H(2)O)].[Zn(C(8)H(3)ClO(4))(C(12)H(12)N(2))]
      (n), one Zn(2+) ion is five-coordin-ated by two O atoms from two different 3
      chloro-benzene-1,2-dicarboxyl-ate ligands, one O atom from a water mol-ecule and
      two N atoms from a 4,4'-dimethyl-2,2'-bipyridine ligand, while the second Zn(2+)
      ion is four-coordinated by two O atoms from two different 3-chloro-benzene-1,2
      dicarboxyl-ate ligands, and two N atoms from a 4,4'-bimethyl-2,2'-bipyridine
      ligand. The crystal structure exhibits a three-dimensional supra-molecular
      structure composed of alternate Zn(C(8)H(3)O(4)Cl)(C(12)H(12)N(2)) and
      Zn(C(8)H(3)O(4)Cl)(C(12)H(12)N(2))(H(2)O) chains, which are linked together by
      face-to-face pi-pi inter-actions [shortest centroid-centroid distances of 3.661
      (4) and 3.6901 (3) A], O-H?O and C-H?O hydrogen bonds.

PMID- 22590090
TI  - catena-Poly[(dichloridozinc)-MU-4,4'-bis-[(1H-imidazol-1-yl)meth-yl]biphenyl
      kappa(2)N(3):N(3')].
AB  - In the title compound, [ZnCl(2)(C(20)H(18)N(4))](n), the Zn(II) ion lies on a
      twofold rotation axis and is four-coordinated in a tetra-hedral geometry defined
      by two Cl anions and two N atoms from two 4,4'-bis-[(imidazol-1-yl)meth
      yl]biphenyl ligands. The mid-point of the ligand is located on an inversion
      center, and shows a trans conformation. The ligands link the Zn(II) ions, forming
      a chain structure along [10-1].

PMID- 22590091
TI  - Bis(2,2'-bipyridine-kappa(2)N,N')tris-(nitrato-kappa(2)O,O')erbium(III).
AB  - The asymmetric unit of the title compound, [Er(NO(3))(3)(C(10)H(8)N(2))(2)],
      contains one-half mol-ecule situated on a twofold rotation axis. The Er(III) ion
      is in a tenfold coordination by six O atoms from three NO(3) (-) anions and four
      N atoms from two 2,2'-bipyridine ligands in a distorted bicapped dodeca-hedral
      geometry. In the crystal, weak C-H?O hydrogen bonds hold the mol-ecules together.

PMID- 22590092
TI  - Trichloridotris{N-[phen-yl(pyridin-2-yl)methyl-idene]hydroxyl-amine
      kappa(2)N,N'}neodymium(III).
AB  - In the title compound, [NdCl(3)(C(12)H(10)N(2)O)(3)], the central Nd(III) ion is
      nine-coordinated by six N atoms from three bidentate chelate N-[phen-yl(pyridin-2
      yl)methyl-idene]hydroxyl-amine ligands and three Cl(-) ions, and displays a
      distorted tricapped trigonal prismatic geometry. The complex mol-ecules are
      stabilized by intra-molecular O-H?Cl hydrogen bonds.

PMID- 22590093
TI  - Bis[MU-N-(2-oxidobenzyl-idene)pyridine-2-carbohydrazidato]bis-[chlorido(methanol
      kappaO)erbium(III)].
AB  - In the binuclear title complex, [Er(2)(C(13)H(9)N(3)O(2))(2)Cl(2)(CH(3)OH)(2)],
      the entire mol-ecule is generated by the application of inversion symmetry. Each
      Er(III) ion is seven-coordinated by two O atoms and one N atom from one N-(2
      oxidobenzyl-idene)pyridine-2-carbohydrazidate (L(2-)) ligand, one O atom and one
      N atom from the symmetry-related L(2-) ligand, one O atom of a methanol mol-ecule
      and one chloride anion. The coordination geometry is based on a pseudo-penta
      gonal bipyramid. Linear supra-molecular chains along [010] are formed in the
      crystal packing through O-H?Cl hydrogen bonds.

PMID- 22590094
TI  - Bis(4,4''-difluoro-1,1':3',1''-terphenyl-2'-carboxyl-ato-kappaO)bis-(3,5-dimethyl
      1H-pyrazole-kappaN(2))manganese(II).
AB  - In the title compound, [Mn(C(19)H(11)F(2)O(2))(2)(C(5)H(8)N(2))(2)], the Mn(2+)
      cation is coordinated by the N atoms of two 3,5-dimethyl-pyrazole ligands and
      carboxyl-ate O atoms from two 4,4''-difluoro-1,1':3',1''-terphenyl-2'-carboxyl
      ato ligands, forming an MnN(2)O(2) polyhedron with a slightly distorted tetra
      hedral coordination geometry. Two intra-molecular hydrogen bonds are observed
      between the carboxyl-ate and pyrazole ligands. The combined influence of the
      sterically hindered carboxyl-ate ligands and the intra-molecular hydrogen-bonding
      inter-actions stabilizes the title compound with a low coordination number of
      four. In the crystal, weak C-H?F and C-H?O hydrogen bonds are observed.

PMID- 22590095
TI  - catena-Poly[[[aqua-[2-(6-chloro-pyridin-3-yl)acetato-kappaO]sodium]-di-MU-aqua]
      monohydrate].
AB  - The crystal structure of the title compound,
      {[Na(C(7)H(5)ClNO(2))(H(2)O)(3)].H(2)O}(n), features polymeric chains along
      [010]. The Na(+) cation is octa-hedrally coordinated by four bridging water mol
      ecules, a terminal water mol-ecule and an O atom derived from a monodentate
      carboxyl-ate ligand. Adjacent polyhedra share two O?O edges. The polymeric chains
      are linked into a three-dimensional network via O-H?O and O-H?N hydrogen bonds.

PMID- 22590096
TI  - catena-Poly[(trans-diaqua-cadmium)-bis-{MU-5-[4-(1H-imidazol-1-yl)phen-yl]tetra
      zol-1-ido}].
AB  - In the title compound, [Cd(C(10)H(7)N(6))(2)(H(2)O)(2)], the Cd(II) atom lies on
      an inversion centre and is coordinated by four N atoms from 5-[4-(1H-imidazol-1
      yl)phen-yl]tetra-zol-1-ide ligands and two O atoms from the coordinated water mol
      ecules in an octa-hedral arrangement. The complex polymeric chains are inter
      connected via inter-molecular water O-H?N hydrogen bonds into a three-dimensional
      network.

PMID- 22590097
TI  - A triclinic polymorph of dichlorido(2-{[2-(isopropyl-ammonio)-eth-yl]imino-methyl
      kappaN}-5-meth-oxy-phenolato-kappaO(1))zinc.
AB  - The title compound, [ZnCl(2)(C(13)H(20)N(2)O(2))], was first reported in the
      monoclinic space group P2(1)/n [Han et al. (2010 ?). Acta Cryst. E66, m469]. This
      investigation reveals a triclinic polymorph in the space group P-1 with an
      asymmetric unit that contains two independent mol-ecules of the mononuclear
      zinc(II) complex. In each mol-ecule, the Zn(II) atoms are coordinated in a
      bidentate fashion by the phenolate O and imine N atoms of the Schiff base ligand.
      Two Cl(-) anions complete the tetra-hedral coordination in each case. The most
      obvious difference between the two forms is that the Zn-L (L = O, N, Cl) bond
      lengths in both unique mol-ecules are longer than those found in the monoclinic
      polymorph, or indeed in other similar complexes. In the crystal, mol-ecules are
      linked through N-H?O and N-H?Cl hydrogen bonds, forming chains along the b axis.

PMID- 22590098
TI  - trans-Dichloridobis[diphen-yl(thio-phen-2-yl)phosphane-kappaP]palladium(II).
AB  - The title compound, trans-[PdCl(2)(C(16)H(13)PS)(2)], forms a monomeric complex
      with a trans-square-planar geometry. The Pd-P bond lengths are 2.3387 (11) A, as
      the Pd atom lies on an inversion point, while the Pd-Cl bond lengths are 2.2950
      (12) A.

PMID- 22590099
TI  - Trichlorido{MU-6,6'-dimeth-oxy-2,2'-[cyclo-hexane-1,2-diylbis(nitrilo-methanylyl
      idene)]diphenolato}dimethano-l-copper(II)samarium(III).
AB  - In the title hetero-dinuclear complex,
      [CuSm(C(22)H(24)N(2)O(4))Cl(3)(CH(3)OH)(2)], the Cu(II) cation is N,N',O,O'
      chelated by a 6,6'-dimeth-oxy-2,2'-[cyclo-hexane-1,2-diylbis(nitrilo-methanylyl
      idene)]diphenolate ligand, and one Cl(-) anion further coordinates to the Cu(II)
      cation to complete the distorted square-pyramidal coordination geometry, while
      the Sm(III) cation is chelated by four O atoms from the same ligand, and is
      further coordinated by two methanol mol-ecules and two Cl(-) anions in an
      bicapped trigonal-prismatic geometry. Intra- and inter-molecular O-H?Cl hydrogen
      bonds are present in the structure.

PMID- 22590100
TI  - Chlorido[1-phenyl-3-(2,3,5,6-tetra-methyl-benz-yl)benzimidazol-2-yl
      idene]silver(I).
AB  - In the title compound, [AgCl(C(24)H(24)N(2))], the terminal phenyl and tetra
      methyl-benzene rings [which form a dihedral angle of 87.92 (14) degrees ] make
      dihedral angles of 59.59 (11) and 83.19 (12) degrees  with respect to the central
      benzimidazole ring system. The Ag-C and Ag-Cl single-bond lengths are 2.087 (3)
      and 2.3267 (9) A. The C-Ag-Cl bond angle is 172.84 (7) degrees . C-H?pi inter
      actions contribute to the stabilization of the crystal structure. A very weak pi
      pi stacking inter-action between adjacent tetra-methyl-benzene rings [centroid
      centroid distance = 4.0610 (18) A] is also observed.

PMID- 22590101
TI  - trans-Dichloridobis(2,4-dimethyl-aniline-kappaN)palladium(II).
AB  - In the title compound, [PdCl(2)(C(8)H(11)N)(2)], the Pd(II) atom is located on a
      crystallographic inversion center and adopts a square-planar coordination
      geometry, with pairs of equivalent ligands in trans positions. In the crystal,
      adjacent mol-ecules are linked with each other through weak N-H?Cl hydrogen bonds
      and pi-pi stacking inter-actions between the phenyl rings [shortest centroid
      centroid distance = 3.720 (2) A], leading to the formation of layers parallel to
      the a-axis direction.

PMID- 22590102
TI  - Poly[[bis-[3-(1H-tetra-zol-1-yl)propanoic acid-kappaN(4)]cadmium]-di-MU-thio
      cyanato-kappa(2)N:S;kappa(2)S:N].
AB  - In the title compound, [Cd(NCS)(2)(C(4)H(6)N(4)O(2))(2)](n), the Cd(II) cation is
      located on an inversion center and is coordinated by two N and two S atoms from
      four SCN(-) anions and two N atoms from two 3-(1H-tetra-zol-1-yl)propanoic acid
      (Htzp) ligands in a distorted octa-hedral geometry. The SCN(-) anions bridge the
      Cd(II) cations into a layer structure parallel to (100). A weak intra-molecular C
      H?N inter-action occurs. The layers are further assembled into a three
      dimensional supra-molecular structure via classical O-H?O hydrogen bonds.

PMID- 22590103
TI  - catena-Poly[(aqua-dimethano-lzinc)-MU-furan-2,5-dicarboxyl-ato
      kappa(3)O(2):O(2),O(2')].
AB  - In the crystal structure of the title compound,
      [Zn(C(6)H(2)O(5))(CH(3)OH)(2)(H(2)O)](n), an infinite chain is formed along the b
      axis by linking of the Zn(OH(2))(CH(3)OH)(2) unit with one carboxyl-ate group of
      the furan-2,5-dicarboxyl-ate ligand. The Zn(II) ion is in a distorted octa-hedral
      environment with one weak coordination [Zn-O(carboxyl-ate) = 2.565 (3) A] and two
      meth-anol mol-ecules located in axial positions. In the chain, O(water)-H?O
      hydrogen bonds are present, while adjacent chains are linked by O(methanol)-H?O
      hydrogen bonds into a layer parallel to (10-2).

PMID- 22590104
TI  - Bis{2-[(4-chloro-phen-yl)imino-meth-yl]pyrrol-1-ido-kappa(2)N,N'}bis-(dimethyl
      amido-kappaN)titanium(IV) toluene monosolvate.
AB  - The mononuclear title compound, [Ti(C(11)H(8)ClN(2))(2)(C(2)H(6)N)(2)].C(7)H(8),
      was synthesized by the reaction of N-(4-chloro-phen-yl)-2-pyrrolylcarbaldimine
      with Ti(C(2)H(6)N)(4). The Ti(IV) ion is situated on a twofold rotation axis and
      displays a distorted octa-hedral geometry defined by four N atoms from two 2-[(4
      chloro-phen-yl)imino-meth-yl]pyrrol-1-ide ligands and two N atoms from two
      dimethyl-amine ligands. The Ti-N(pyrrole) bond length [2.1041 (19) A] is longer
      than the Ti-N(dimethyl-amine) bond length [1.9013 (19) A]; the imine N atom
      exhibits the longest Ti-N bond [2.3152 (17) A]. The toluene solvent mol-ecule is
      located on a twofold rotation axis running through the C atom of the methyl
      group. Consequently, the H atoms of the latter are rotationally disordered. The
      compound contains no markable hydrogen-bonding inter-actions.

PMID- 22590105
TI  - catena-Poly[[[tetra-aqua-copper(II)]-MU-4,4'-bipyridyl-kappa(2)N:N'] tetra
      fluorido-succinate tetra-hydrate].
AB  - In the title compound, {[Cu(C(10)H(8)N(2))(H(2)O)(4)](C(4)F(4)O(4)).4H(2)O}(n),
      the Cu(II) atom adopts an elongated octa-hedral geometry because of the Jahn
      Teller effect. Both cation and anion have crystallographic twofold rotation
      symmetry with the twofold axes passing through the Cu and N atoms and through the
      midpoint of the central C-C bond. The 4,4'-bipyridyl ligand links the Cu(II)
      atoms into a linear chain along the b axis. O-H?O hydrogen-bonding inter-actions
      between the cationic chains and the tetra-fluorido-succinate anions and the free
      water mol-ecules generate a three-dimensional supra-molecular network.

PMID- 22590106
TI  - Bis(acetato-kappaO)bis-[2-(pyridin-2-yl)ethanol-kappa(2)N,O]copper(II).
AB  - The title compound, [Cu(CH(3)COO)(2)(C(7)H(9)NO)(2)], is a monomeric complex with
      an octa-hedral geometry. The Cu(II) atom is located on an inversion center and is
      coordinated by acetate and 2-(pyridin-2-yl)ethanol ligands. The acetate group is
      coordinated in a monodentate manner, while the 2-(pyridin-2-yl)ethanol is
      coordinated as a bidentate ligand involving the endocyclic N atom and the hy
      droxy O atom of the ligand side chain. An intra-molecular hydrogen bond is
      observed between the hy-droxy O atom and the non-coordinated acetate O atom. No
      classical inter-molecular hydrogen-bond contacts were observed. However, the
      crystal packing is effected by C-H?O inter-actions, which link the mononuclear
      entities into layers parallel to the bc plane.

PMID- 22590107
TI  - Diaqua-bis-[5-(pyrazin-2-yl-kappaN(1))-3-(pyridin-4-yl)-1H-1,2,4-triazol-1-ido
      kappaN(1)]cobalt(II) methanol disolvate.
AB  - The Co(II) ion in the title mononuclear compound,
      [Co(C(11)H(7)N(6))(2)(H(2)O)(2)].2CH(3)OH, is located on an inversion center and
      is six-coordinated in a distorted octa-hedral geometry defined by four N atoms
      from two deprotonated 5-(pyrazin-2-yl-kappaN)-3-(pyridin-4-yl)-1H-1,2,4-triazol-1
      ide (ppt) ligands and two water mol-ecules. In the crystal, the complex mol
      ecules and lattice methanol mol-ecules are linked via O-H?N and O-H?O hydrogen
      bonds, generating a two-dimensional supra-molecular network parallel to (001). pi
      pi inter-actions between the triazole and pyrazine rings and between the pyridine
      rings are present [centroid-centroid distances = 3.686 (3) and 3.929 (4) A,
      respectively].

PMID- 22590108
TI  - catena-Poly[[aqua-(2-iodo-benzoato-kappaO)cobalt(II)]-MU-aqua-MU-2-iodo-benzoato
      kappa(2)O:O'].
AB  - The asymmetric unit of the polymeric title compound,
      [Co(C(7)H(4)IO(2))(2)(H(2)O)(2)](n), contains one Co(II) cation, two iodo
      benzoate anions and two water mol-ecules. One iodo-benzoate anion and one water
      mol-ecule bridge adjacent Co cations, forming a polymeric chain running along the
      a axis, while the other iodo-benzoate anion and water mol-ecule coordinate in a
      monodentate manner to the Co(II) cation, completing the slightly distorted octa
      hedral geometry. In the two independent anionic ligands, the carboxyl-ate groups
      are twisted away from the attached benzene rings by 51.38 (18) and 39.89 (11)
      degrees , and the two benzene rings are nearly perpendicular to each other with a
      dihedral angle of 86.09 (10) degrees . Intra-molecular O-H?O hydrogen bonds
      between coordinating water mol-ecules and adjacent carboxyl-ate O atoms help to
      stabilize the mol-ecular structure. In the crystal, weak C-H?O hydrogen bonds
      link the polymeric chains into a three-dimentional supra-molecular network.

PMID- 22590109
TI  - Bis(MU-2-{bis-[(2-oxidobenzyl-idene)amino]-meth-yl}phenolato)bis-[(tetra-hydro
      furan)-samarium(III)] tetra-hydro-furan disolvate.
AB  - In the centrosymmetric binuclear complex of the title solvate,
      [Sm(2)(C(21)H(15)N(2)O(3))(2)(C(4)H(8)O)(2)].2C(4)H(8)O, the Sm(III) is coordin
      ated in a distorted monocapped octa-hedral geometry by four O atoms and two N
      atoms from two tridentate deprotonated 2-{bis-[(2-oxidobenzyl-idene)amino]-meth
      yl}phenolate ligands and an O atom of a tetra-hydro-furan (THF) mol-ecule. The
      Sm?Sm distance in the complex is 3.8057 (4) A. Parts of the coordinating THF mol
      ecule are disordered over two sets of sites in a 0.56 (3):0.44 (3) ratio. The
      complex and solvent mol-ecules are linked into a three-dimensional structure via
      C-H?O hydrogen-bonding inter-actions.

PMID- 22590110
TI  - cis-Dichlorido[2,3-dimethyl-3-(4,4,5,5-tetra-methyl-1,3,2lambda(5)-dioxaphospho
      lan-2-yl-oxy)butan-2-olato-kappa(2)O,P]oxido(triphenyl-phosphane
      kappaP)rhenium(V).
AB  - The title compound, cis-[Re(C(12)H(24)O(4)P)Cl(2)O(C(18)H(15)P)], was prepared
      from the analogous trans isomer [Glowiak et al. (2000 ?). Polyhedron, 19, 2667
      2672] by a trans-cis isomerization reaction. The Re(V) atom adopts a distorted
      octa-hedral coordination geometry. Besides being coordinated by the oxide and the
      butano-late O atoms, the Re(V) atom is coordinated by a pair of chloride ligands
      and two P atoms in cis positions with respect to each other. In the crystal,
      adjacent mol-ecules are linked by weak C-H?Cl inter-actions, forming a three
      dimensional network.

PMID- 22590111
TI  - Bis[(1H-1,2,3-benzotriazol-1-yl)methyl 2,2-dimethyl-propano-ato
      kappaN(3)]dichlorido-copper(II).
AB  - In the title compound, [CuCl(2)(C(12)H(15)N(3)O(2))(2)], the Cu(II) ion is
      located on an inversion center and is four-coordinated in a distorted square
      planar geometry by two chloride anions and two N atoms from two (1H-1,2,3
      benzotriazol-1-yl)methyl 2,2-dimethyl-propano-ate ligands. The Cl-Cu-N angles of
      90.55 (9) and 89.45 (9) degrees  are close to ideal values. In the crystal, weak
      pi-pi stacking inter-actions are observed between inversion-related benzene rings
      [centroid-centroid distance = 4.0028 (6) A].

PMID- 22590112
TI  - Carbonyl-bis-(triphenyl-phosphane-kappaP)(eta(2)-1-vinyl-pyrrolidin-2-one
      kappaO)ruthenium(0).
AB  - The 1-vinyl-pyrrolidin-2-one ligand in the title compound,
      [Ru(C(6)H(9)NO)(C(18)H(15)P)(2)(CO)], coordinates to the Ru(0) atom with the
      olefin double bond and the ketone O atom. The Ru(0) atom adopts a distorted
      trigonal-bipyramidal coordination geometry, with the C O ligand and the ketone O
      atom occupying the axial positions. The two triphenyl-phosphane ligands are cis
      to each other. The olefinic C=C bond is almost coplanar with the Ru(0) atom and
      the two P atoms (maximum deviation of 0.0516 A from the mean plane defined by the
      five constituent atoms). The coordinated C=C bond has a length of 1.449 (3) A,
      which is significantly longer than that of a free C=C bond (1.34 A). There are
      two C-H?pi inter-actions involving neighbouring phenyl rings in the mol-ecule. In
      the crystal, mol-ecules are linked via two further C-H?pi inter-actions.

PMID- 22590113
TI  - Bis[MU-1-hexyl-3-(2,3,5,6,8,9,11,12-octa-hydro-1,4,7,10,13-benzopenta-oxacyclo
      penta-decin-15-yl)urea]bis-(azido-sodium) chloro-form disolvate.
AB  - In the title compound, [Na(2)(N(3))(2)(C(21)H(34)N(2)O(6))(2)].2CHCl(3), the
      sodium cation is hepta-coordinated by five O atoms of the crown ether unit of the
      1-hexyl-3-(2,3,5,6,8,9,11,12-octa-hydro-1,4,7,10,13-benzopenta-oxacyclo-penta
      decin-15-yl)urea (L) ligand, the O atom of the urea group of the second, symmetry
      related L ligand, and one N atom of the azide anion. The experimentally
      determined distance 2.472 (2) A between the terminal azide N atom and the sodium
      cation is substanti-ally longer than that predicted from density functional
      theory (DFT) calculations (2.263 A). The crown ethers complexing the sodium
      cation are related by an inversion centre and form dimers. The urea groups of the
      two L ligands are connected in a head-to-tail fashion by classical N-H?N hydrogen
      bonding inter-actions and form a ribbon-like structure parallel to the b axis.
      Parallel ribbons are weakly linked through C-H?N, C-H?O and C-H?pi inter-actions.

PMID- 22590114
TI  - catena-Poly[[(p-toluene-sulfonato-kappaO)silver(I)]-MU-1,3-bis-(pyridin-4
      yl)propane-kappa(2)N:N'].
AB  - In the title compound, [Ag(C(7)H(7)O(3)S)(C(13)H(14)N(2))](n), the Ag(I) ion is
      coordinated in a T-shape by two N atoms from two symmetry-related 1,3-bis
      (pyridin-4-yl)propane ligands and one O atom from a p-toluene-sulfonate ligand,
      forming a one-dimensional zigzag chain along [001]. In the crystal, weak C-H?O
      hydrogen bonds and weak Ag?Ag inter-actions [3.2628 (5) A] are observed.

PMID- 22590115
TI  - catena-Poly[[silver(I)-MU-4,4'-bipyridine-kappa(2)N:N'] 4-[2-(4-carb-oxy-phen-yl)
      1,1,1,3,3,3-hexa-fluoro-propan-2-yl]benzoate].
AB  - Assembly of the flexible dicarb-oxy-lic ligand 4-[2-(4-carboxyphenyl)-1,1,1,3,3,3
      hexafluoropropan-2-yl]benzoate and 4,4'-bipyridine as co-ligand with Ag(I) ions
      resulted in the formation of the polymeric title compound,
      {[Ag(C(10)H(8)N(2))](C(17)H(9)F(6)O(4))}(n), in which the metal atoms are bridged
      by the 4,4'-bipyridine ligands, generating cationic chains extending along [010].
      The dihedral angles between the benzene rings in the anion and the pyridine rings
      in the cation are 72.42 (9) and 9.36 (10) degrees , respectively. The mol-ecular
      conformation of the anion is stabilized by intra-molecular C-H?F hydrogen bonds.
      In the crystal, the anions inter-act with the cationic chains via C-H?O hydrogen
      bonds, forming layers parallel to (001), in which weak pi-pi stacking inter
      actions [centroid-centroid distances = 3.975 (3)-4.047 (3) A] involving the
      pyridine rings of adjacent 4,4'-bipyridine ligands are present. The planes are
      further assembled into a three-dimensional network by O-H?O hydrogen bonds.

PMID- 22590116
TI  - Poly[bis-(1-carbamoylguanidinium) [tri-MU-chlorido-dichloridobismuthate(III)]].
AB  - The structure of the title organic-inorganic hybrid compound,
      {(C(2)H(7)N(4)O)(2)[BiCl(5)]}(n), consists of corrugated chains parallel to [100]
      of corner-joined [BiCl(6)] octa-hedra, separated by layers of organic 1
      carbamoylguanidinum cations. The crystal cohesion is achieved by N-H?O and N-H?Cl
      hydrogen bonds, which link the organic and inorganic parts of the structure.

PMID- 22590117
TI  - Dipotassium tetra-kis-(thio-cyanato-kappaS)palladate(II)-(2,2'-bipyrimidine
      kappa(2)N(1),N(1'))bis-(thio-cyanato-kappaS)palladium(II) (1/2).
AB  - The asymmetric unit of the title compound,
      K(2)[Pd(NCS)(4)].2[Pd(NCS)(2)(C(8)H(6)N(4))], contains two crystallographically
      independent half-mol-ecules of the anionic Pd(II) complex, two K(+) cations and
      two independent neutral Pd(II) complexes; an inversion centre is located at the
      centroid of each anionic complex. In the anionic complexes, each Pd(II) ion is
      four-coordinated in an almost regular square-planar environment by four S atoms
      from four SCN(-) anions, and the PdS(4) unit is exactly planar. In the neutral
      complexes, the Pd(II) ion has a slightly distorted square-planar coordination
      environment defined by two pyrimidine N atoms derived from a chelating 2,2'
      bipyrimidine ligand and two mutually cis S atoms from two SCN(-) anions. Both
      2,2'-bipyrimidine ligands are almost planar [dihedral angle between the rings =
      3.98 (16) and 4.57 (17) degrees ] and also chelate to a potassium ion from their
      other two N atoms. In the crystal, the K(+) ions inter-act with various S and N
      atoms of the ligands, forming a three-dimensional polymeric network, in which the
      shortest K?K contacts between the KN(7)S polyhedra are 4.4389 (17) and 4.4966
      (18) A. Intra- and inter-molecular C-H?S and C-H?N hydrogen bonds are also
      observed.

PMID- 22590118
TI  - (2,2'-Biquinoline-kappa(2)N,N')dibromidopalladium(II).
AB  - The Pd(II) ion in the title complex, [PdBr(2)(C(18)H(12)N(2))], is four
      coordinated in a distorted square-planar environment by the two N atoms from the
      chelating 2,2'-biquinoline (Biqu) ligand and two mutually cis Br(-) anions. The
      Biqu ligand is not planar, the dihedral angle between the quinoline systems being
      17.2 (2) degrees . In the crystal, the complex mol-ecules are connected by C-H?Br
      hydrogen bonds, forming chains along the c axis. When viewed down the b axis,
      successive chains are stacked in opposite directions. Intra-molecular C-H?Br
      hydrogen bonds are also observed.

PMID- 22590119
TI  - Bis[MU-N'-(adamantan-1-ylcarbon-yl)-2-oxidobenzohydrazidato(3-)]tetra-pyridine
      trinickel(II) dimethyl-formamide monosolvate monohydrate.
AB  - In the title trinuclear Ni(II) compound,
      [Ni(3)(C(18)H(19)N(2)O(3))(2)(C(5)H(5)N)(4)].C(3)H(7)NO.H(2)O, three Ni(II)
      cations are bridged by two N'-(adamantan-1-ylcarbon-yl)-2-oxidobenzohydrazidate
      trianions. The central Ni(II) cation has a distorted octa-hedral N(4)O(2)
      coordination environment where a reverse torsion occurs between the two bridging
      ligands, whereas the two Ni(II) cations on the sides each adopt an N(2)O(2)
      square-planar coordination. Weak intra-molecular C-H?O and C-H?N inter-actions
      help to stabilize the mol-ecular structure. In the crystal, the lattice water mol
      ecule links with the Ni(II) complex and dimethyl-formamide solvent mol-ecule via
      O-H?O hydrogen bonding.

PMID- 22590120
TI  - catena-Poly[(dichloridozinc)-MU-1-{4-[(1H-imidazol-1-yl)meth-yl]benz-yl}-1H
      imidazole-kappa(2)N(3):N(3')].
AB  - The asymmetric unit of the title compound, [ZnCl(2)(C(14)H(14)N(4))](n), contains
      a Zn(II) ion situated on a twofold rotation axis and one-half of a 1-{4-[(1H
      imidazol-1-yl)meth-yl]benz-yl}-1H-imidazole (L) ligand with the benzene ring
      situated on an inversion center. The Zn(II) ion is coordinated by two chloride
      anions and two N atoms from two L ligands in a distorted tetra-hedral geometry.
      The L ligands bridge ZnCl(2) fragments into polymeric chains parallel to [20-1].

PMID- 22590121
TI  - Poly[diaqua-bis-{MU-5-[4-(1H-imidazol-1-ylmethyl)phen-yl]tetra
      zolato}copper(II)].
AB  - In the title compound, [Cu(C(11)H(9)N(6))(2)(H(2)O)(2)](n), the Cu(II) atom lies
      on an inversion center and is coordinated by four N atoms from four 5-[4-(1H
      imidazol-1-ylmethyl)phen-yl]tetra-zolate ligands and two water mol-ecules in a
      distorted octa-hedral geometry. The ligands bridge the Cu(II) atoms, leading to
      the formation of a two-dimensional network parallel to (100). The structure is
      further stabilized by O-H?N hydrogen bonds within the network.

PMID- 22590122
TI  - Tetra-kis(1-phenyl-1H-imidazole-kappaN(3))bis-(thio-cyanato-kappaN)nickel(II).
AB  - The title compound, [Ni(NCS)(2)(C(9)H(8)N(2))(4)], crystallizes with two
      independent half-mol-ecules in the asymmetric unit and the Ni(II) ions situated
      on centres of symmetry. In both independent mol-ecules, the Ni(II) ion displays a
      compressed octa-hedral environment formed by four N atoms from the 1-phenyl-1H
      imidazole ligands, which define the equatorial plane, with a mean Ni-N distance
      of 2.119 (11) A, and two axial N atoms from two NCS(-) anions, with a mean Ni-N
      distance of 2.079 (7) A. The crystal packing exhibits weak inter-molecular S?S
      contacts of 3.411 (2) A.

PMID- 22590123
TI  - catena-Poly[[[penta-aqua-cerium(III)]-MU-pyridine-2,4,6-tricarboxyl-ato
      kappa(4)N,O(2),O(6):O(6')] tetra-hydrate].
AB  - The Ce(III) atom in the title compound,
      {[Ce(C(8)H(2)NO(6))(H(2)O)(5)].4H(2)O}(n), is N,O,O'-chelated by the carboxyl-ate
      trianion and is coordinated by five water mol-ecules; a carboxyl O atom from an
      adjacent trianion bridges the Ce(III) atom, resulting in a chain running along
      the a axis. The nine atoms surrounding the metal atom comprise a tricapped
      trigonal-prismatic polyhedron. The coordinated and lattice water mol-ecules inter
      act with each other and with the carboxyl O atoms by O-H?O hydrogen bonds,
      generating a three-dimensional network.

PMID- 22590124
TI  - Bis-(methane-sulfonato-kappaO)(5,10,15,20-tetra-phenyl-porphyrinato
      kappa(4)N,N',N'',N''')tin(IV) chloro-form tris-olvate.
AB  - In the crystal structure of the title compound,
      [Sn(C(44)H(28)N(4))(CH(3)O(3)S)(2)].3CHCl(3), the Sn(IV) ion is located on an
      inversion center and is octa-hedrally coordinated. The porphyrin N atoms occupy
      the equatorial positions while the axial positions are occupied by the O atoms of
      the methane-sulfonate anions. The phenyl rings make dihedral angles of 77.02 (13)
      and 87.89 (14) degrees  with the porphyrin ring. Of the three solvent chloro-form
      mol-ecules, one is disordered over a twofold rotation axis. In the crystal a
      three-dimensional assembly is accomplished via C-H?O hydrogen bonds between the H
      atoms of the phenyl groups in the porphyrin ring and the O atoms of the methane
      sulfonate ligands.

PMID- 22590125
TI  - catena-Poly[[[aqua-(pyrazine-2-carboxamide-kappa(2)N(1),O)zinc]-MU-pyrazine-2
      carboxamide-kappa(3)N(1),O:N(4)] dinitrate].
AB  - In the crystal of the title compound,
      {[Zn(C(5)H(5)N(3)O)(2)(H(2)O)](NO(3))(2)}(n), the Zn(II) cation is N,O-chelated
      by two pyrazine-2-carboxamide (PCA) ligands and is further coordinated by one
      water mol-ecule and by one pyrazine-N atom from an adjacent PCA ligand in a
      distorted ZnN(3)O(3) octa-hedral geometry. One of the two independent PCA ligands
      bridges two Zn(II) cations, forming a zigzag polymeric chain running along the c
      axis. In the crystal, the NO(3) (-) anions link to the chain via O-H?O and N-H?O
      hydrogen bonding. Weak inter-molecular C-H?O inter-actions also occur.

PMID- 22590126
TI  - [MU-1,6-Bis(diphenyphosphan-yl)hexane-1:2kappa(2)P:P']deca-carbonyl
      1kappa(3)C,2kappa(3)C,3kappa(4)C-triangulo-triruthenium(0).
AB  - The title triangulo-triruthenium(0) compound, [Ru(3)(C(30)H(32)P(2))(CO)(10)],
      contains a triangle of singly bonded Ru atoms. The phosphane-bridged Ru-Ru
      distance [2.9531 (2) A] is significantly longer than the non-bridged Ru-Ru
      distances [2.8842 (2) and 2.8876 (2) A] . The bis-(diphenyl-phosphan-yl)hexane
      ligand bridges the Ru-Ru bond. Each phosphane-substituted Ru atom bears one
      equatorial and two axial terminal carbonyl ligands, whereas the unsubstituted Ru
      atom bears two equatorial and two axial terminal carbonyl ligands. The dihedral
      angles between the benzene rings attached to each P atom are 72.75 (7) and 82.02
      (7) degrees . The mol-ecular structure is stabilized by an intra-molecular C-H?O
      hydrogen bond involving a methyl-ene group of the phosphane ligand and an axial
      carbonyl O atom, which generates an S(6) ring motif. In the crystal, mol-ecules
      are linked via C-H?O hydrogen bonds into layers parallel to (100).

PMID- 22590127
TI  - Bis(3,5-dimethyl-1H-pyrazole-kappaN(2))bis-(3,3'',5,5''-tetra-methyl-[1,1':3',1''
      terphen-yl]-2'-carboxyl-ato-kappaO)iron(II) dichloro-methane monosolvate.
AB  - In the title compound, [Fe(C(23)H(21)O(2))(2)(C(5)H(8)N(2))(2)].CH(2)Cl(2), the
      Fe(2+) cation is coordinated by the N atoms of two 3,5-dimethyl-pyrazole ligands
      and the carboxyl-ate O atoms from two tetra-methyl-terphenyl-carboxyl-ate
      ligands, forming an FeN(2)O(2) polyhedron with a slightly distorted tetra-hedral
      coordination geometry. Intra-molecular N-H?O and C-H?O hydrogen-bonding inter
      actions stabilize the mol-ecular conformation. The dihedral angles formed by the
      central benzene ring with the outer benzene rings of the terphenyl groups are
      47.92 (8), 59.38 (8), 48.24 (8) and 52.37 (8) degrees . The dichloro-methane
      solvent mol-ecule inter-acts with the complex mol-ecule via a C-H?O hydrogen
      bond. In the crystal, centrosymmetrically related complex mol-ecules are linked
      into dimers through pairs of C-H?O hydrogen bonds.

PMID- 22590128
TI  - Poly[[tris-(MU-4,4'-bipyridine-kappa(2)N:N')bis-(MU-l-lysinato
      kappa(3)N(1),O(1):O(1'))dizinc(II)] tetra-nitrate 0.6-hydrate dimethyl-formamide
      disolvate].
AB  - In the title compound,
      {[Zn(2)(C(6)H(14)N(2)O(2))(2)(C(10)H(8)N(2))(3)](NO(3))(4).0.6H(2)O.2C(3)H(7)NO}(
      ), the Zn(II) ion is six-coordinated with a distorted octa-hedral geometry by two
      carboxyl-ate O atoms and one amino N atom from two l-lysinate (l-lys) ligands,
      and three N atoms from three 4,4'-bipyridine (4,4'-bipy) ligands. The Zn(II) ions
      are connected by the carboxyl-ate groups of the l-lys ligands in the a-axis
      direction and the bridging 4,4'-bipy ligands in the b- and c-axis directions,
      forming a three-dimensional cationic framework with channels along [100]. The
      nitrate anions and solvent water and dimethyl-formamide (DMF) mol-ecules are
      located in the channels and linked to the cationic framework by N-H?O and O-H?O
      hydrogen bonds. The occupancy of the water mol-ecule was fixed at 0.6. One of the
      DMF mol-ecules is disordered over two sets of sites, with an occupancy ratio of
      0.632:0.368 (11).

PMID- 22590129
TI  - Bis{4-phenyl-1-[1-(pyridin-2-yl-kappaN)ethyl-idene]thio-semicarbazidato
      kappa(2)N(1),S}cadmium.
AB  - The reaction of cadmium acetate dihydrate with 2-acetyl-pyridine (4-phenyl-thio
      semicarbazone) yielded the title compound, [Cd(C(14)H(13)N(4)S)(2)]. The Cd(II)
      atom is six-coordin-ated in a distorted octa-hedral environment by two deproton
      ated thio-semicarbazone ligands acting in a tridentate chelating mode through two
      N and one S atoms, forming metalla-rings. In the crystal, mol-ecules are
      connected through inversion centers via pairs of N-H?S inter-actions, building a
      one-dimensional hydrogen-bonded polymer along [0-1-1].

PMID- 22590130
TI  - catena-Poly[[silver(I)-MU-1,2-bis-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2
      yl)ethane-kappa(2)N:N'] perchlorate hemihydrate].
AB  - In the title coordination polymer, {[Ag(C(12)H(20)N(2)O(2))]ClO(4).0.5H(2)O}(n),
      the Ag(I) cation is coordinated by two N atoms from two 1,2-bis-(4,4-dimethyl-4,5
      dihydro-1,3-oxazol-2-yl)ethane (L) ligands in a nearly linear geometry [N-Ag-N =
      171.07 (8) degrees ]. The L ligand bridges adjacent Ag(+) cations, forming a
      polymeric chain running along the c axis. The lattice water mol-ecule is situated
      on a twofold rotation axis, and links to the perchlorate anion via an O-H?O
      hydrogen bond. The long Ag?O separation of 3.200 (4) A indicates a weak inter
      action between the perchlorate anion and the Ag(I) cation. Weak C-H?O hydrogen
      bonding occurs between the chain and the lattice water mol-ecule and between the
      chain and perchlorate anions. Both five-membered rings of the L ligand display
      envelope conformations; in one five-membered ring, the flap C atom is disordered
      on opposite sides of the ring with occupancies of 0.65 and 0.35.

PMID- 22590131
TI  - [(E)-Oxido(pyridin-2-yl-methyl-idene)amine-kappa(2)N,N'][(E)-N-(pyridin-2-yl
      methyl-idene)hydroxyl-amine-kappa(2)N,N']silver(I) perchlorate-bis-[(E)-N
      (pyridin-2-yl-methyl-idene)hydroxyl-amine-kappa(2)N,N']silver(I) (1/1).
AB  - In the title salt co-crystal,
      [Ag(C(6)H(5)N(2)O)(C(6)H(6)N(2)O)]ClO(4).[Ag(C(6)H(6)N(2)O)(2)], the asymmetric
      unit comprises a [Ag(LH)(2)](+) cation, a perchlorate anion and a neutral (LH)AgL
      mol-ecule, where LH is pyridine-2-carboxaldoxime. Both silver-containing species
      feature N,N'-chelating LH and L ligands, which define an N(4) donor set that is
      highly distorted [dihedral angles between AgC(2)N(2) chelate rings = 45.7 (3) and
      44.3 (2) degrees , respectively] owing, in part, to the close approach of a
      neighbouring Ag atom, leading to an argentophilic inter-action [Ag?Ag = 3.1868
      (11) A]. The mol-ecular conformations are stabilized by intra-molecular O-H?O
      hydrogen bonds. In the crystal, O-H?O inter-actions lead to supra-molecular
      chains along [010]. Chains aggregate into layers in the ab plane, defining
      channels along [100] in which reside the perchlorate anions; the latter are
      disordered over two overlapped orientations in a 50:50 ratio.

PMID- 22590132
TI  - catena-Poly[[(2-amino-1,3-benzothia-zole-6-carboxyl-ato-kappa(2)O,O')(2,2'
      bipyridyl-kappa(2)N,N')cadmium]-MU-2-amino-1,3-benzothia-zole-6-carboxyl-ato
      kappa(3)N(1):O,O'].
AB  - In the title coordination polymer, [Cd(C(8)H(5)N(2)O(2)S)(2)(C(10)H(8)N(2))](n),
      the Cd(II) ion is coordinated by a bidentate 2,2-bipyridyl ligand, two O,O'
      chelating 2-amino-1,3-benzothia-zole-6-carboxyl-ate (ABTC) ligands and one N
      bonded ABTC ligand. The resulting CdN(3)O(4) coordination polyhedron approximates
      to a very distorted penta-gonal bipramid with one O and one N atom in axial
      positions. One of the ABTC ligands is bridging to an adjacent metal atom,
      generating an infinite chain propagating in [100]. A three-dimensional network is
      constructed from N-H?O and N-H?N hydrogen bonds and aromatic pi-pi stacking inter
      actions [centroid-centroid separations = 3.641 (2) and 3.682 (3) A].

PMID- 22590133
TI  - Poly[[dodeca-aqua-(MU(4)-benzene-1,4-dicarboxyl-ato)(MU(2)-4,4'-bipyridine
      kappa(2)N:N')dicerium(III)] bis-(benzene-1,4-dicarboxyl-ate)].
AB  - The asymmetric unit of the title compound,
      {[Ce(2)(C(8)H(4)O(4))(C(10)H(8)N(2))(H(2)O)(12)](C(8)H(4)O(4))(2)}(n), consists
      of half a Ce(III) cation, a quarter of a coordinated benzene-1,4-dicarboxyl-ate
      (bdc(2-)) dianion, a quarter of a 4,4'-bipyridine (bpy) mol-ecule, three water
      mol-ecules and a half of an uncoordinated benzene-1,4-dicarboxyl-ate dianion. The
      Ce(III) ion is located on a twofold rotation axis and exhibits a distorted
      trigonal prism square-face tricapped coordination geometry. The coordinated and
      uncoordinated bdc(2-) ions and the bpy mol-ecule lie about special positions of
      site symmetries 2/m, m and 2/m, respectively. The Ce(III) ions are bridged by the
      bdc(2-) and bpy ligands, giving a sheet structure parallel to the ac plane. The
      uncoordinated bdc(2-) dianion exists between the sheets and links the sheets by
      inter-molecular O-H?O hydrogen bonds between the uncoordinated bdc(2-) and
      coordinated water mol-ecules. A pi-pi stacking inter-action between the
      uncoordinated bdc(2-) dianion and the bpy ligand [centroid-centroid distance =
      3.750 (4) A] is also observed.

PMID- 22590134
TI  - Di-MU-bromido-bis-({2-[(4,6-dimethyl-pyrimidin-2-yl)disulfan-yl]-4,6-dimethyl
      pyrimidine-kappa(2)N(1),S(2)}copper(I)).
AB  - The title dinuclear complex, [Cu(2)Br(2)(C(12)H(14)N(4)S(2))(2)], is located
      about an inversion center. The Cu(I) ion is coordinated in a distorted tetra
      hedral geometry by two bridging Br atoms in addition to an N and an S atom from
      the 2-[(4,6-dimethyl-pyrimidin-2-yl)disulfan-yl]-4,6-dimethyl-pyrimidine ligand.
      In the crystal, pi-pi stacking inter-actions are observed with a centroid
      centroid distance of 3.590 (2) A.

PMID- 22590135
TI  - catena-Poly[[(2-amino-pyrimidine-kappaN(1))(thio-cyanato-kappaS)mercury(II)]-MU
      thio-cyanato-kappa(2)S:N].
AB  - In the title coordination polymer, [Hg(NCS)(2)(C(4)H(5)N(3))], the Hg(II) atom is
      four-coordinated by one aromatic N atom from a 2-amino-pyrimidine ligand, one S
      atom from a terminal thio-cyanate ligand, and one S atom and one N atom from a
      bridging thio-cyanate ligand. The crystal structure features polymeric chains
      running along the b axis which are stabilized by N-H?N hydrogen bonds.

PMID- 22590136
TI  - N-Ferrocenymethyl-N-phenyl-propionamide.
AB  - In the title compound, [Fe(C(5)H(5))(C(15)H(16)NO)], the two cyclo-penta-dienyl
      (Cp) rings are nearly parallel to each other, forming a dihedral angle of 3.7 (1)
      degrees , and adopt a staggered conformation. The amide group is almost
      perpendicular to the plane of the substituted Cp ring, with a C-N-C-C torsion
      angle of 101.3 (2) degrees , and the N and O atoms in the ethanoyl group are
      coplanar, with a C-N-C-O torsion angle of -0.7 (3) degrees . Weak C-H?O hydrogen
      bonds link adjacent mol-ecules.

PMID- 22590137
TI  - Bis(MU-4,4;6,6-bis-(biphenyl-2,2'-diyldi-oxy)-2,2-bis-{2-[5-(pyridin-4-yl)-1,3,4
      oxadiazol-2-yl]phen-oxy}cyclo-triphosphazene)di-MU-chlorido-bis-[chlorido
      copper(II)].
AB  - In the crystal of the title compound, [Cu(2)Cl(4)(C(50)H(32)N(9)O(8)P(3))(2)],
      the binuclear mol-ecule is located across an inversion center. Each Cu(2+) cation
      is coordinated by two pyridine N atoms from symmetry-related 4,4;6,6-bis
      (biphenyl-2,2'-diyldi-oxy)-2,2-bis-{2-[5-(pyridin-4-yl)-1,3,4-oxadiazol-2-yl]phen
      oxy}cyclo-triphosphazene (L) ligands, a pair of bridging Cl(-) anions and a
      terminal Cl(-) anion, forming a distorted CuCl(3)N(2) square-pyramidal geometry.
      Weak intra-molecular C-H?O and inter-molecular C-H?N inter-actions occur in the
      crystal.

PMID- 22590138
TI  - catena-Poly[[[aqua-(1,10-phenanthroline-kappa(2)N,N')manganese(II)]-{MU-4,4'-[(4
      carb-oxy-benz-yl)nitrilo]-dibenzoato-kappa(4)O,O':O'',O'''}] monohydrate].
AB  - The title compound, {[Mn(C(22)H(15)NO(6))(C(12)H(8)N(2))(H(2)O].H(2)O}(n), was
      obtained under solvothermal conditions. The Mn(2+) cation exhibits a distorted
      penta-gonal-bipyramidal MnN(2)O(5) coordination sphere with the water O atom and
      one of the phenanthroline N atoms in the axial positions. The cation is bridged
      by the doubly deprotonated 4,4'-[(4-carb--oxy-benz-yl)nitrilo]-dibenzoate ligand,
      generating a polymeric chain parallel to [100]. O-H?O hydrogen bonding, as well
      as pi-pi inter-actions between neighbouring phenanthroline ligands, with centroid
      centroid distances of 3.695 (1) A, lead to the construction of a three
      dimensional network.

PMID- 22590139
TI  - Tetra-kis(4-meth-oxy-anilinium) hexa-chloridobismuthate(III) chloride
      monohydrate.
AB  - In the crystal of the title compound, (C(7)H(10)NO)(4)[BiCl(6)]Cl.H(2)O, the
      Bi(III) cation is located on an inversion center and coordinated by six Cl(-)
      anions in a slightly distorted octa-hedral geometry; the uncoordinated Cl(-)
      anion and lattice water mol-ecule are located on a twofold rotation axis. Two
      independent 4-meth-oxy-anilinium cations are linked to the Bi complex, the
      uncoordinated Cl(-) anion and lattice water mol-ecule via N-H?Cl and N-H?O
      hydrogen bonds.

PMID- 22590140
TI  - trans-Diaqua-bis-[5-(pyridine-3-carboxamido)-tetra-zolido-kappa(2)O,N(1)]zinc
      dihydrate.
AB  - The title compound, [Zn(C(7)H(5)N(6)O)(2)(H(2)O)(2)].2H(2)O, consists of one
      Zn(II) ion located on the crystallographic inversion centre, two 5-(pyridine-3
      carboxamido)-tetra-zolide ligands, two coordinated water mol-ecules and two free
      water mol-ecules. The Zn(II) ion adopts a slightly distorted octa-hedral
      coordination geometry formed by the N,O-chelating ligands and two O water atoms.
      The pyridine N atoms are not coordinated. In the crystal, complex mol-ecules are
      connected by N-H?O, O-H?N and O-H?O hydrogen bonds, forming a three-dimensional
      network.

PMID- 22590141
TI  - catena-Poly[[diaqua-bis-(2-ethyl-1H-imidazole-kappaN(3))cadmium]-MU-sulfato
      kappa(2)O:O'].
AB  - In the title one-dimensional coordination polymer,
      [Cd(SO(4))(C(5)H(8)N(2))(2)(H(2)O)(2)](n), the Cd(II) atom (site symmetry 2) is
      coordinated by two sulfate O atoms, two water mol-ecules and two 2-ethyl
      imidazole ligands in a distorted cis-CdN(2)O(4) octa-hedral geometry. The water
      mol-ecules have a cis disposition. The bridging sulfate ions (site symmetry 2)
      link the Cd(II) ions into a polymeric chain extending along [001]. The chains are
      linked by N-H?O and O-H?O hydrogen bonds. The terminal -CH(3) group of the ligand
      is disordered over two orientations in a 0.61 (5):0.39 (5) ratio.

PMID- 22590142
TI  - Butyl-triethyl-ammonium tetra-chlorido-ferrate(III).
AB  - In the title compound, (C(10)H(24)N)[FeCl(4)], no classical hydrogen bonds are
      observed. The butyl-triethyl-ammonium cations inter-act with the tetra-hedral
      [FeCl(4)](-) anion through weak C-H?Cl inter-actions, forming a three-dimensional
      network.

PMID- 22590143
TI  - Bis(butyl-triethyl-ammonium) di-MU-bromido-bis-[dibromido-mercurate(II)].
AB  - In the title mol-ecular salt, (C(10)H(24)N)(2)[Hg(2)Br(6)], the complete anion is
      generated by crystallographic inversion symmetry, forming a pair of edge-sharing
      HgBr(4) tetra-hedra. In the crystal, the cations and anions are linked by weak C
      H?Br inter-actions.

PMID- 22590144
TI  - Tris(2-methyl-piperidinium) tetra-chlorido-ferrate dichloride.
AB  - The asymmetric unit of the title salt, (C(6)H(14)N)(3)[FeCl(4)]Cl(2), consists of
      a tetra-hedral tetra-chloro-ferrate anion, three independent 2-methyl
      piperidinium cations and two chloride ions. All the piperidine rings adopt chair
      conformations. In the crystal, the organic cations and the free chloride anions
      are linked into chains parallel to the a axis by N-H?Cl hydrogen bonds.

PMID- 22590145
TI  - catena-Poly[[[aqua-bis-(1H-imidazole-kappaN(3))copper(II)]-MU-furan-2,5-di-car
      boxylato-kappa(2)O(2):O(5)] trihydrate].
AB  - In the title cooridnation polymer,
      {[Cu(C(6)H(2)O(5))(C(3)H(4)N(2))(2)(H(2)O)].3H(2)O}(n), an infinite chain is
      formed along [001] by linking of the Cu(C(3)N(2)H(4))(2)(H(2)O) entities with two
      bridging monodentate carboxyl-ate groups of two different furan-2,5-dicarboxyl
      ate dianions. The geometry of the Cu(2+) ion is a square-based pyramid with the
      water atom in the apical position and the ligand O and N atoms in a trans
      orientation. The dihedral angle between the imidazole planes is 83.96 (14)
      degrees . O(w)-H?O and N(i)-H?O (w = water and i = imidazole) hydrogen bonds help
      to establish the packing.

PMID- 22590146
TI  - Poly[[bis-(MU-4,4'-bipyridine-kappa(2)N:N')copper(I)] perchlorate 0.24-hydrate].
AB  - The title copper(I) polymeric compound,
      {[Cu(C(10)H(8)N(2))(2)]ClO(4).0.24H(2)O}(n), obtained by the reaction of
      Cu(ClO(4))(2) and 4,4'-bipyridine (4,4'-bpy) under hydro-thermal conditions,
      features a fourfold-inter-penetrated diamondoid coordination framework. The
      asymmetric unit consists of two Cu(I) atoms, three 4,4'-bpy ligands in general
      positions and two halves of two centrosymmetric 4,4'-bpy ligands, two ClO(4) (-)
      anions and water mol-ecule with a site-occupancy factor of 0.480 (17). The Cu(I)
      atoms are in a distorted tetra-hedral coordination environment and are bridged by
      4,4'-bpy ligands, forming a diamondoid cationic polymeric framework that encloses
      two symmetry-independent channels along [100], which accommodate perchlorate
      anions and water mol-ecules.

PMID- 22590147
TI  - Heptaaqua-(3,4,5,6-tetra-chloro-phthalato-kappaO(1))erbium(III) 2-carb-oxy
      3,4,5,6-tetra-chloro-benzoate-3,4,5,6-tetra-chloro-phthalic acid-water (1/1/1).
AB  - In the three-dimensional tetra-chloro-phthalate-bridged title complex
      [Er(C(8)Cl(4)O(4))(H(2)O)(7)](C(8)HCl(4)O(4)).C(8)H(2)Cl(4)O(4).H(2)O, the
      Er(III) ion is coordinated in form of a distorted square antiprism by an O atom
      of a tetra-chloro-phthalate ligand and by seven water O atoms. Extensive hydrogen
      bonds establish a layered network structure extending parallel to (001).

PMID- 22590148
TI  - Bis{S-benzyl 3-[(6-methyl-pyridin-2-yl)methyl-idene]dithio-carbazato}nickel(II).
AB  - The asymmetric unit of the title compound, [Ni(C(15)H(14)N(3)S(2))(2)], consists
      of two independent mol-ecules with similar configurations. Each Ni(2+) cation is
      coordinated in a cis-mode by two tridentate N,N',S-chelating Schiff base ligands,
      creating a distorted octa-hedron [the smallest angle being 77.57 (7) degrees  and
      the widest being 168.97 (7) degrees  for one mol-ecule, and 78.04 (7) and 167.55
      (7) degrees  for the second mol-ecule]. The dihedral angle between the mean
      coordination planes of the two ligands is 86.76 (7) degrees  for one and 89.99
      (7) degrees  for the second mol-ecule. pi-pi inter-actions between neighbouring
      pyridine rings with plane-to-plane distances of 3.540 (1) and 3.704 (1) A are
      observed.

PMID- 22590149
TI  - 1-Cyano-methyl-1,4-diazo-niabicyclo-[2.2.2]octane tetra-chloridocobaltate(II).
AB  - In the title salt, (C(8)H(15)N(3))[CoCl(4)], the four chloride anions coordinate
      the Co(II) ion in a distorted tetra-hedral geometry. In the crystal, N-H?Cl
      hydrogen bonds link cations and anions into chains running along the c axis. The
      crystal packing is further stabilized by weak C-H?Cl and C-H?N inter-actions.

PMID- 22590150
TI  - Dicarbon-yl[4-(2,6-dimethyl-phenyl-amino)-pent-3-en-2-onato
      kappa(2)N,O]rhodium(I).
AB  - In the title compound, [Rh(C(13)H(16)NO)(CO)(2)], a square-planar coordination
      geometry is observed around the Rh(I) atom, formed by the N and O atoms of the
      bidentate ligand and two C atoms from two carbonyl ligands. The Rh(I) atom is
      displaced from the plane through these surrounding atoms by 0.0085 (2) A. The
      dihedral angle between the benzene ring and the N-C-C-C-O plane is 89.82 (6)
      degrees , and the N-Rh-O bite angle for the bidentate ligand is 90.53 (6) degrees
      . An inter-molecular C-H?O inter-action is observed between a methyl group of the
      benzene ring and a carbonyl O atom.

PMID- 22590151
TI  - Bis(MU-4-nitro-2-{[2-(oxidometh-yl)phen-yl]imino-meth-yl}phenolato)bis
      [chlorido(dimethyl sulfoxide)-iron(III)] dimethyl sulfoxide disolvate.
AB  - In the centrosymmetric dimeric title complex,
      [Fe(2)(C(14)H(10)N(2)O(4))(2)Cl(2)(C(2)H(6)OS)(2)].2C(2)H(6)OS, two
      {Fe(L)Cl(DMSO)} units (L is the tridentate ligand 4-nitro-2-{[2-(oxidometh
      yl)phen-yl]imino-meth-yl}phenolate; DMSO is dimethyl sulfoxide) are bridged by
      two O atoms, with an Fe?Fe separation of 3.1838 (8) A. The coordination
      polyhedron of the Fe(III) atoms can be described as distorted octa-hedral, with
      four Fe-O, one Fe-N and one Fe-Cl coordination bonds. The L ligand is not planar,
      the dihedral angle between the 2-(oxidometh-yl)phen-yl]imino and 4-nitro-2-(imino
      meth-yl)phenolate planes being 48.54 (9) degrees . The solvent DMSO molecule is
      disordered over two orientations with equal occupancy.

PMID- 22590152
TI  - Bis[3-(pyrazin-2-yl)-5-(pyridin-2-yl-kappaN)-1,2,4-triazol-1-ido
      kappaN(1)]copper(II).
AB  - In the mononuclear title complex, [Cu(C(11)H(7)N(6))(2)], the Cu(II) atom lies on
      a crystallographic inversion centre and is coordinated by four N atoms from two
      bidentate chelate monoanionic 3-(pyrazin-2-yl)-5-(pyridin-2-yl-1,2,4-triazol-1
      ido ligands, two from the triazolide rings [Cu-N = 1.969 (2) A] and two from the
      pyridine rings [Cu-N = 2.027 (2) A], giving a slightly distorted square-planar
      geometry.

PMID- 22590153
TI  - [4,4'-(Ethane-1,2-diyldinitrilo)-bis-(pent-2-en-2-olato)]copper(II) 0.25-hydrate.
AB  - In the title compound, [Cu(C(12)H(18)N(2)O(2))].0.25H(2)O, the coordination of
      the O,N,N',O'-tetra-dentate ligand results in a cis-CuN(2)O(2) square-planar
      geometry for the metal ion and the presence of two six-membered and one five
      membered chelate rings. The complete complex mol-ecule is close to planar (r.m.s.
      deviation = 0.047 A). The uncoordinated water mol-ecule (O-atom site symmetry 2)
      was modelled as half occupied. In the crystal, C-H?O(w) and O(w)-H?O (w = water)
      hydrogen bonds link the components into layers parallel to ab plane.

PMID- 22590154
TI  - Bis(2-methyl-piperidinium) penta-chlorido-anti-monate(III).
AB  - The asymmetric unit of the title compound, (C(6)H(14)N)(2)[SbCl(5)], contains one
      cation and half of the anion on a special position (specifically, the Sb(III) ion
      and three chloride anions are situated on a mirror plane). In the [SbCl(5)](2-)
      unit, the Sb(III) ion is coordinated by five chloride anions [Sb-Cl = 2.3721 (11)
      2.6656 (12) A] in a distorted square-pyramidal geometry. However, one chloride
      anion from a neighbouring [SbCl(5)](2-) unit provides a short Sb?Cl contact of
      3.3600 (12) A and completes the Sb coordination environment up to an elongated
      octa-hedron. In the crystal, N-H?Cl hydrogen bonds link cations and anions into
      columns propagating along [100].

PMID- 22590155
TI  - Di-MU(2)-chlorido-dichloridoocta-methyldi-MU(3)-oxido-tetra-tin(IV)
      bis[chloridodimeth-yl(pyrrolidine-1-carbodithio-ato-kappa(2)S,S')tin(IV)].
AB  - In the title co-crystal,
      [Sn(4)(CH(3))(8)Cl(4)O(2)].2[Sn(CH(3))(2)Cl(C(4)H(8)NS(2))], all the Sn(IV) atoms
      are in distorted trigonal-bipyramidal environments. In the mononuclear species,
      the carbodithio-ate ligand is unsymmetrically coordinated to the Sn(IV) atom,
      with Sn-S distances of 2.6722 (12) and 2.4706 (11) A. All atoms with the
      exception of the methyl groups and one of the pyrrolidine ring CH(2) groups lie
      on a crystallographic mirror plane. The pyrrolidine ring exhibits an envelope
      conformation; the C atom at the flap is disordered above and below the plane of
      symmetry with fixed occupation factors of 0.50. The centrosymmetric dimer species
      consists of a central Sn(2)O(2) unit with two adjacent Sn(2)OCl four-membered
      rings.

PMID- 22590156
TI  - Poly[(acetato-kappa(2)O,O')aqua-(MU(4)-1H-benzimidazole-5,6-dicarboxyl-ato
      kappa(6)N(3):O(5),O(5'):O(5),O(6):O(6'))cerium(III)].
AB  - In the title compound, [Ce(C(9)H(4)N(2)O(4))(C(2)H(3)O(2))(H(2)O)](n), the
      Ce(III) ion is coordinated by five O atoms and one N atom from four 1H
      benzimidazole-5,6-dicarboxyl-ato (L) ligands and by two O atoms from an acetate
      ligand and one aqua ligand, forming a slightly distorted tricapped trigonal
      prismatic geometry. The L ligands are bridging, forming a layered polymer
      parallel to (010). In the crystal, O-H?O and N-H?O hydrogen bonds connect the
      polymer layers into a three-dimensional network.

PMID- 22590157
TI  - Aqua-trichlorido(1-cyano-methyl-4-aza-1-azoniabicyclo-[2.2.2]octane
      kappaN(4))copper(II) monohydrate.
AB  - The asymmetric unit of the title compound, [CuCl(3)(C(8)H(14)N(3))(H(2)O)].H(2)O,
      comprises a neutral complex and a mol-ecule of free water. The complex contains
      coordinated Cu(II) ions, with Cu-Cl distances ranging from 2.3471 (8) to 2.4011
      (8) A, and with Cu-N and Cu-O distances of 2.0775 (19) and 2.0048 (18) A,
      respectively. The resulting coordination polyhedron is a trigonal bipyramid with
      the Cl atoms in the equatorial plane. In the crystal, O-H?Cl and O-H?O hydrogen
      bonds link the mol-ecules into a three-dimensional structure.

PMID- 22590158
TI  - (4-Aza-1-azoniabicyclo-[2.2.2]octane-kappaN(4))trichloridocobalt(II).
AB  - In the title compound, [CoCl(3)(C(6)H(13)N(2))], the tetra-hedrally coordinated
      Co(II) ion has Co-Cl distances ranging from 2.2220 (11) to 2.2449 (9) A and a Co
      N distance of 2.056 (2) A. In the crystal, N-H?Cl hydrogen bonds link mol-ecules
      into chains in [010]. Weak C-H?Cl inter-actions stabilize further the crystal
      packing.

PMID- 22590159
TI  - (2,2'-Bipyrimidine-kappa(2)N(1),N(1'))bis-(thio-cyanato-kappaN)platinum(II).
AB  - In the title complex, [Pt(NCS)(2)(C(8)H(6)N(4))], the Pt(II) ion is four
      coordinated in a distorted square-planar environment defined by two pyrimidine N
      atoms derived from a chelating 2,2'-bipyrimidine (bpym) ligand and two mutually
      cis N atoms from two SCN(-) anions. The thio-cyanate ligands are almost linear,
      displaying N-C-S bond angles of 178.6 (11) and 173.7 (11) degrees , and the N
      atoms are slightly bent coordinated to the Pt atom with Pt-N-C bond angles of
      172.7 (9) and 160.4 (10) degrees . In the crystal, mol-ecules are held together
      by C-H?S hydrogen bonds. Intra-molecular C-H?N hydrogen bonds are also observed.

PMID- 22590160
TI  - (Acetato-kappaO)(2-bromo-6-{[3-(dimethyl-aza-nium-yl)propyl-imino-kappaN]meth
      yl}phenolato-kappaO)(thio-cyanato-kappaN)zinc.
AB  - In the title compound, [Zn(CH(3)COO)(NCS)(C(12)H(17)BrN(2)O)], the Zn(II) atom is
      four-coordinated in a distorted tetra-hedral geometry, binding to a phenolate O
      and an imine N atom of the Schiff base ligand, the O atom of an acetate ligand
      and one thio-cyanate N atom. In the crystal, mol-ecules are linked via pairs of N
      H?O hydrogen bonds, forming inversion dimers.

PMID- 22590161
TI  - N-Benzyl-N,N-dimethyl-octa-decan-1-aminium (2-thioxo-1,3-dithiole-4,5-dithiol-ato
      kappa(2)S(4),S(5))nickelate(III).
AB  - The asymmtric unit of the title compound, (C(27)H(50)N)[Ni(C(3)S(5))(2)],
      contains two N-benzyl-N,N-dimethyl-octa-decan-1-aminium cations, [BDA](+), and
      two [Ni(dmit)(2)](-) anions (dmit = 2-thioxo-1,3-dithiole-4,5-dithiol-ate). The
      C(18) chains in both cations adopt almost ideal extended conformations. The
      Ni(III) atoms are coordinated by two S,S'-bidentate ligands, generating NiS(4)
      square planes. Short Ni?S [3.734 (2) A] and S?S contacts [3.5438 (15) A] occur in
      the crystal structure; if these are considered to be bonding inter-actions, then
      infinite sheets of anions parallel to (111) arise.

PMID- 22590162
TI  - Poly[di-MU(9)-citrato-cobalt(II)tetra-sodium].
AB  - The title compound, [CoNa(4)(C(6)H(5)O(7))(2)](n), was obtained under hydro
      thermal conditions as a minor product. The Co(2+) cation is located on a
      crystallographic inversion center and is coordinated by six O atoms from two
      different citrate units, forming a [Co(C(6)H(5)O(7))(2)](4-) building unit with
      Co-O bond lengths between 2.0578 (17) and 2.0813 (16) A. The structure features
      two crystallographically independent Na(+) ions. The first Na(+) cation is five
      coordinated by O atoms of five carboxylate groups from four different citrate
      anions. The second Na(+) cation is surrounded by six O atoms of five carboxylate
      groups from five different citrate anions. The carboxylate groups of the citrate
      are completely depronona-ted, the hydroxyl group, however, is not. It is
      coordinated to the Co(2+) cation, and through an O-H?O hydrogen bond connected to
      a neighboring [Co(C(6)H(5)O(7))(2)](4-) building unit. The coordination modes of
      the carboxyl-ate O atoms vary, with one O atom being coordinated to three
      different Na(+) cations, three are bridging O atoms bound to two Na(+) cations
      and two are connected to a Co(2+) cation and a Na(+) cation, respectively.
      Through these inter-connections, the basic [Co(C(6)H(5)O(7))(2)](4-) building
      units are linked with each other through coordination of their carboxyl-ate
      groups to the Na(+) cations, forming a three-dimensional framework.

PMID- 22590163
TI  - Bis(3-methyl-anilinium) hexa-chlorido-stannate(IV) dihydrate.
AB  - In the title compound, (C(7)H(10)N)(2)[SnCl(6)].2H(2)O, the Sn(IV) atom lies on a
      site with symmetry 2/m. One of the Cl atoms lies on a mirror plane and the 3
      methyl-anilinium cation is also situated on a mirror plane. The water mol-ecule
      is located on a twofold rotation axis. The H atoms of the methyl and ammonium
      groups and the solvent water mol-ecule are disordered by symmetry. In the
      crystal, N-H?Cl, O-H?Cl and N-H?O hydrogen bonds connect the organic cations, the
      inorganic octahedrally shaped anions and the water mol-ecules.

PMID- 22590164
TI  - Poly[[chloridodimethanol(MU(3)-pyridine-2,3-dicarboxyl-ato)europium(III)]
      methanol monosolvate].
AB  - The asymmetric unit of the title compound,
      {[Eu(C(7)H(3)NO(4))Cl(CH(3)OH)(2)].CH(3)OH}(n), contains one Eu(III) ion, one
      pyridine 2,3-dicarboxylate dianion (PDC), two CH(3)OH mol-ecules coordinating to
      the metal atom, one coordinating chloride and one lattice occluded CH(3)OH mol
      ecule. In the crystal, each PDC anion coordinates to three adjacent Eu(III) ions
      by the pyridine N and O atoms of the carboxyl-ate groups. The Eu(III) cation is
      eightfold coordinated by four carboxyl-ate O atoms, one pyridine N atom, two MeOH
      and one chloride anion in the form of a distorted polyhedron. Extended
      coordination of the PDC ligand lead to the formation of a two-dimensional
      coordination polymer parallel to (10-1).

PMID- 22590165
TI  - Bis(2-amino-benzothia-zol-3-ium) bis-(7-oxabicyclo-[2.2.1]heptane-2,3-dicarboxyl
      ato-kappa(3)O(2),O(3),O(7))nickelate(II) hexa-hydrate.
AB  - In the title compound, (C(7)H(7)N(2)S)(2)[Ni(C(8)H(8)O(5))(2)].6H(2)O, the Ni(II)
      cation is located on an inversion center and is O,O',O''-chelated by two symmetry
      related 7-oxabicyclo-[2.2.1]heptane-2,3-dicarboxyl-ate anions in a distorted octa
      hedral geometry. The 2-amino-benzothia-zol-3-ium cation links with the Ni complex
      anion via N-H?O hydrogen bonding. Extensive O-H?O and N-H?O hydrogen bonds
      involving the lattice water mol-ecules also occur in the crystal structure.

PMID- 22590166
TI  - Bis(2-amino-benzothia-zol-3-ium) bis-(7-oxabicyclo-[2.2.1]heptane-2,3-dicarboxyl
      ato-kappa(3)O(2),O(3),O(7))zincate hexa-hydrate.
AB  - In the title hydrated mol-ecular salt,
      (C(7)H(7)N(2)S)(2)[Zn(C(8)H(8)O(5))(2)].6H(2)O, which is isotypic with its
      Mn(II), Co(II) and Ni(II) analogues, the Zn(2+) ion lies on a crystallographic
      inversion centre and a distorted ZnO(6) octa-hedral coordination geometry arises
      from the two doubly deprotonated O,O',O''-tridentate ligands. In the crystal, the
      components are linked by N-H?O(a), N-H?O(w), O(w)-H?O(a) and O(w)-H?O(w) hydrogen
      bonds (w = water and a = anion).

PMID- 22590167
TI  - Poly[[dodeca-aqua-bis-(MU(3)-pyridine-2,6-dicarboxyl-ato)tetra-kis-(MU(2)
      pyridine-2,6-dicarboxyl-ato)tri-calciumdieuropium(III)] 10.5-hydrate].
AB  - In the title compound, {[Ca(3)Eu(2)(C(7)H(3)NO(4))(6)(H(2)O)(12)].10.5H(2)O}(n),
      the Eu(III) ion is nine-coordinated by three tridentate pyridine-2,6-dicarboxyl
      ate (PDA) ligands, forming a [Eu(PDA)(3)](3-) building block. The Ca(2+) ions
      adopt two types of coordination geometries. One Ca(2+) ion, lying on a twofold
      rotation axis, is eight-coordinated by four carboxyl-ate O atoms from four PDA
      ligands and four water mol-ecules, and the other two Ca(2+) ions, each lying on
      an inversion center, are six-coordinated by two carboxyl-ate O atoms from two PDA
      ligands and four water mol-ecules. The carboxyl-ate groups bridge the Eu(III) and
      Ca(2+) ions into a three-dimensional porous framework, with channels extending
      along [010] and [001] in which lattice water mol-ecules are located. Two of the
      lattice water mol-ecules are disordered over two sets of sites with equal
      occupancy and one water mol-ecule is 0.25-occupied. Numerous O-H?O hydrogen bonds
      involving the water mol-ecules and carboxyl-ate O atoms are present.

PMID- 22590168
TI  - 1-Cyano-methyl-1,4-diazo-niabicyclo-[2.2.2]octane tetra-chloridocadmate(II).
AB  - In the title salt, (C(8)H(15)N(3))[CdCl(4)], four Cl atoms coordinate the Cd(II)
      atom in a slightly distorted tetra-hedral geometry. In the crystal, each
      [CdCl(4)](2-) anion is connected to the 1-cyano-methyl-1,4-diazo-niabicyclo
      [2.2.2]octane dications by N-H?Cl hydrogen bonds, forming chains parallel to
      [001]. C-H?Cl inter-actions also occur.

PMID- 22590169
TI  - trans-Diaqua-bis-(1H imidazolium-4,5-di-carboxyl-ato-kappa(2)O(4),O(5))magnesium.
AB  - The title compound, [Mg(C(5)H(3)N(2)O(4))(2)(H(2)O)(2)], consists of
      centrosymmetric neutral monomers in which two O,O'-bidentate imidazolinium-4,5
      dicarboxyl-ate ligands are bonded to the Mg(II) ion. One of the carboxyl protons
      is transferred to the N atom of the imidazole ring. The octa-hedral metal-ion
      coordination is completed by two trans water O atoms. In the crystal, mol-ecules
      are linked by N-H?(O,O) and O-H?O hydrogen bonds.

PMID- 22590170
TI  - catena-Poly[[[diaqua-nickel(II)]-MU-pyrazine-2-carboxyl-ato-silver(I)-MU-pyrazine
      2-carboxyl-ato] nitrate dihydrate].
AB  - In the polymeric complex of the title compound,
      {[AgNi(C(5)H(3)N(2)O(2))(2)(H(2)O)(2)]NO(3).2H(2)O}(n), the Ag(I) ion displays an
      angular coordination geometry with two N atoms from pyrazine-2-carboxyl-ate
      ligands, and the Ni(II) ion is hexa-coordinated by two O atoms from two water mol
      ecules, two O and two N atoms from pyrazine-2-carboxyl-ate ligands in a distorted
      octa-hedral geometry. In the crystal, the Ag(I) and Ni(II) ions lie on a mirror
      plane and an inversion centre, respectively. The complex chains, the nitrate ions
      and the uncoordinated water mol-ecules are linked together through O-H?O hydrogen
      bonds and weak Ag?O inter-actions [2.619 (17)-2.749 (17) A] into a three
      dimensional network.

PMID- 22590171
TI  - catena-Poly[[penta-MU-benzoato-MU-chlorido-dioxanedineodymium(III)] dioxane 2.5
      solvate].
AB  - The asymmetric unit of the title compound,
      [Nd(2)(C(6)H(5)COO)(5)Cl(C(4)H(8)O(2))].2.5C(4)H(8)O(2), consists of two Nd(III)
      ions bridged by one Cl(-) ion, five benzoate ions and one coordinating 1,4
      dioxane mol-ecule. One Nd(III) ion is nine-coordinate, with a very distorted
      monocapped square-anti-prismatic geometry. It is coordinated by two chelating
      carboxyl-ate groups, three monodentate carboxyl-ate groups, one chloride ion and
      one dioxane mol-ecule. A second independent Nd(III) ion is eight-coordinated in a
      distorted square-anti-prismatic geometry by one chelating carboxyl-ate group,
      five monodentate carboxyl-ate groups and one chloride ion. The chains of the
      extended structure are parallel to the crystallographic b axis. There is a small
      amount of void space which is filled with five disordered dioxane solvent mol
      ecules per unit cell. The intensity contribution of the disordered solvent
      molecules was removed by applying the SQUEEZE procedure in PLATON [Spek (2009).
      Acta Cryst. D65, 148-155].

PMID- 22590172
TI  - Di-MU-bromido-bis-{[N,N-dimethyl-N'-(thio-phen-2-yl-methyl-idene)ethane-1,2
      diamine]-copper(I)]}.
AB  - In the crystal structure of the title compound, [Cu(2)Br(2)(C(9)H(14)N(2)S)(2)],
      the mol-ecule resides about a crystallographic inversion center. The coordination
      sphere around each copper ion has a distorted tetra-hedral geometry, with
      ligation by two bridging bromide ions, an amine N atom and an imine N atom. The
      thio-phene ring is disordered over two sites, with occupancies of 0.719 (3) and
      0.281 (3). Weak C-H?pi inter-actions feature in the crystal packing.

PMID- 22590173
TI  - catena-Poly[[(2,2'-bipyidine-2kappa(2)N,N')-MU-cyanido-1:2kappa(2)N:C
      dicopper(I)]-MU-bromido-[(2,2'-bipyidine-2kappa(2)N,N')-MU-cyanido-1:2kappa(2)N:C
      dicopper(I)]-MU-cyanido-kappa(2)N:C].
AB  - In the title complex, [Cu(4)Br(CN)(3)(C(10)H(8)N(2))(2)](n), the four independent
      Cu(I) atoms are all in distorted trigonal-planar geometries. One is formed by one
      N atom and one C atom from two cyanide groups and one Br atom, one is formed by
      two N atoms from two cyanide groups and one Br atom, and the other two are formed
      by two N atoms from a chelating 2,2'-bipyridine (bpy) ligand and one C atom from
      a cyanide group. The structure exhibits a zigzag chain backbone along [101]
      constructed by bromide and cyanide anions bridging the Cu(I) atoms, with the
      [Cu(bpy)(CN)] units pointing laterally.

PMID- 22590174
TI  - Chlorido[N,N'-dibenzyl-N,N'-bis-(pyridin-2-ylmeth-yl)ethane-1,2-diamine]
      copper(II) perchlorate methanol monosolvate.
AB  - In the title solvated mol-ecular salt, [CuCl(C(28)H(30)N(4))]ClO(4).CH(3)OH, the
      Cu(2+) ion is coordinated by the N,N',N'',N'''-tetra-dentate ligand and a
      chloride ion, generating a very distorted square-based pyramidal CuN(4)Cl
      coordination geometry with the Cl(-) ion in the basal position. In the crystal,
      the solvent mol-ecules and anions are linked by weak O-H?O hydrogen bonding.

PMID- 22590175
TI  - Bis(dicyanamido-kappaN)tetra-kis-(pyridazine-kappaN)nickel(II).
AB  - Reaction of nickel(II) chloride with sodium dicyanamide and pyridazine leads to
      single crystals of the title compound, [Ni{N(CN)(2)}(2)(C(4)H(4)N(2))(4)], in
      which the Ni(II) cation is octa-hedrally coordinated by two dicyanamide anions
      and four pyridazine ligands into a discrete complex that is located on a center
      of inversion.

PMID- 22590176
TI  - Poly[[diaqua-bis-(MU(3)-3,5-dicarb-oxy-benzo-ato-kappa(3)O(1):O(3):O(5))bis
      (MU(3)-5-carb-oxy-ben-zene-1,3-dicarboxyl-ato
      kappa(3)O(1):O(3):O(5))tetrakis(methylformamide-kappaO)tri-man-ganese(II)]
      dimethyl-formamide tetra-solvate].
AB  - In the title complex,
      {[Mn(3)(C(9)H(4)O(6))(2)(C(9)H(5)O(6))(2)(C(3)H(7)NO)(4)(H(2)O)(2)].4C(3)H(7)NO}(
      ), one Mn(II) ion sits on an inversion center, and is six-coordinated by four O
      atoms from four anions (monoanionic and dianionic) derived from benzene-1,3,5
      tricarboxylic acid and by two dimethyl-formamide (DMF) mol-ecules in a slightly
      distorted octa-hedral geometry. The other Mn(II) ion is six-coordinated by four O
      atoms from four monoanionic and dianionic ligands, one DMF mol-ecule and one
      water mol-ecule in a distorted octa-hedral geometry. The monoanionic and
      dianionic ligands bridge the Mn(II) ions, resulting in the formation of a layered
      structure parallel to (111) in which all of the carboxyl-ate groups of the
      anionic ligands coordinate the Mn(II) ions in a monodentate manner. Intra- and
      inter-molecular O-H?O hydrogen bonds are present in the structure.

PMID- 22590177
TI  - Poly[[MU-(1-ammonio-ethane-1,1-di-yl)bis-(hydrogenphospho
      nato)]diaquachloridodisodium]: a powder X-ray diffraction study.
AB  - The title compound, [Na(2)(C(2)H(8)NO(6)P(2))Cl(H(2)O)(2)](n), has a polymeric
      two-dimensional structure extending parallel to (001). The asymmetric unit
      contains two Na(+) cations located on a centre of symmetry and on a mirror plane,
      respectively, one half of a bis-phospho-nate anion (the entire anion is completed
      by mirror symmetry), one chloride anion on a mirror plane and one water mol-ecule
      in general positions. The two Na(+) cations exhibit distorted octa-hedral
      NaCl(2)O(4) coordination polyhedra, each consisting of two deprotonated O atoms
      of the bis-phospho-nate anion, of two water mol-ecules and of two chloride
      anions. Strong O-H?O hydrogen bonds between the -OH group and one of the free O
      atoms of the bis-phospho-nate anion connect adjacent layers along [100],
      supported by N-H?Cl inter-actions. Intra-layer O-H?O and N-H?O hydrogen bonds are
      also observed.

PMID- 22590178
TI  - Tris(1,10-phenanthrolin-1-ium) hexa-cyanidoferrate(III) ethanol monosolvate
      trihydrate.
AB  - The asymmetric unit of the title complex,
      (C(12)H(9)N(2))(3)[Fe(CN)(6)].C(2)H(5)OH.3H(2)O, consists of two half
      [Fe(CN)(6)](3-) anions located on inversion centers, three 1,10-phenanthrolin-1
      ium cations, [Hphen](+), an ethanol and three water solvent mol-ecules. The
      average Fe-C and C-N bond lengths are 1.942 (6) and 1.154 (3) A, respectively,
      while the Fe-C-N angles deviate slightly from linearity with values ranging from
      177.8 (2) to 179.7 (2) degrees . The Fe(III) atoms adopt a distorted octa-hedral
      geometry. All the species are linked through O-H?N, N-H?O and O-H?O hydrogen
      bonding inter-actions, resulting in a three-dimensional supra-molecular network.

PMID- 22590179
TI  - Hexa-kis-(dimethyl sulfoxide-kappaO)calcium MU(6)-oxido-dodeca-kis-MU(2)-oxido
      hexa-oxido-hexa-tungstate(VI).
AB  - In the title compound, [Ca(C(2)H(6)OS)(6)][W(6)O(19)], the cation and anion both
      have a crystallographically imposed centre of symmetry. The Ca(II) atom in the
      cation is coordinated by six O atoms from six dimethyl sulfoxide ligands in a
      distorted octa-hedral geometry. The [W(6)O(19)](2-) isopolyanion possesses the
      well-known Lindqvist structure in which each W(VI) atom is coordinated by four
      MU(2)-O, one terminal O and one MU(6)-O atom.

PMID- 22590180
TI  - Bis(3-acetyl-pyridine-kappaN)diaqua-bis-(seleno-cyanato-kappaN)cobalt(II).
AB  - In the crystal structure of the title compound,
      [Co(NCSe)(2)(C(7)H(7)NO)(2)(H(2)O)(2)], the Co(2+) cation is coordinated by two
      seleno-cyanate anions, two 3-acetyl-pyridine ligands and two water mol-ecules
      within a slightly distorted CoN(4)O(2) octa-hedron. The asymmetric unit consists
      of one Co(2+) cation, which is located on a center of inversion, as well as one
      seleno-cyanate anion, one 3-acetyl-pyridine ligand and one water mol-ecule in
      general positions. Whereas one of the water H atoms makes a classical O-H?O
      hydrogen bond, the other shows a O-H?Se inter-action.

PMID- 22590181
TI  - catena-Poly[[bis-(3-acetyl-pyridine-kappaN)cadmium]-di-MU-seleno-cyanato
      kappa(2)N:Se;kappa(2)Se:N].
AB  - In the crystal structure of the title compound, [Cd(NCSe)(2)(C(7)H(7)NO)(2)](n),
      the Cd(2+) cation is coordinated by two 3-acetyl-pyridine ligands and four MU-1,3
      bridging seleno-cyanate anions within a slightly distorted CdN(4)Se(2) octa
      hedron. The asymmetric units consists of one Cd(2+) cation, which is situated on
      a center of inversion, as well as one seleno-cyanate anion and one 3-acetyl
      pyridine ligand in general positions. The metal cations are MU-1,3-bridged via
      the seleno-cyanate anions into chains along the a axis.

PMID- 22590182
TI  - Poly[[MU-ethane-1,2-diyl bis-(pyridine-3-carboxyl-ate)](MU-tetra-fluorido
      borato)silver(I)].
AB  - In the title compound, [Ag(BF(4))(C(14)H(12)N(2)O(4))](n), the coordination of
      the Ag(+) ion is trigonal-bipyramidal with the N atoms of two ethane-1,2-diyl bis
      (pyridine-3-carboxyl-ate) ligands in the apical positions and three F atoms
      belonging to different tetra-fluorido-borate anions in the equatorial plane. The
      material consists of infinite chains of [Ag(C(14)H(12)N(2)O(4))] units running
      along [001], held together by BF(4) (-) bridging anions.

PMID- 22590184
TI  - Poly[di-MU(3)-acetato-MU(8)-(naphthalene-1,5-disulfonato)-dilead(II)].
AB  - In the polymeric title complex, [Pb(2)(CH(3)CO(2))(2)(C(10)H(6)O(6)S(2))](n), the
      acetate anion functions in a chelating mode and both O atoms also coordinate to
      adjacent Pb(II) atoms. The naphthalene-1,5-disulfonate dianion, which lies on a
      center of inversion, is connected to four Pb(II) atoms. The bridging modes of the
      monoanion and dianion give rise to a three-dimensional coordination polymer. The
      Pb(II) atom is eight-coordinate in the form of an undefined coordination
      polyhedron.

PMID- 22590183
TI  - Tetra-kis(triphenyl-phosphane-kappaP)silver(I) tetra-fluorido-borate.
AB  - The title complex, [Ag(C(18)H(15)P)(4)]BF(4), was prepared by the reaction of
      silver(I) tetra-fluorido-borate and triphenyl-phosphane in the presence of 1,2
      bis-(pyridin-2-yl)ethyl-ene. The Ag(I) atom is tetra-hedrally coordinated by four
      P atoms from triphenyl-phosphane (PPh(3)) ligands. Due to symmetry, the tetra
      fluorido-borate anion is disordered over three positions (each with one third
      occupancy). The tetra-fluorido-borate anion does not coordinate to the Ag(I)
      atom.

PMID- 22590185
TI  - Iodido(tri-tert-butyl-phosphane-kappaP)gold(I).
AB  - The Au(I) atom of the title compound, [AuI(C(12)H(27)P)], shows an almost linear
      coordination, with a P-Au-I angle of 178.52 (3) degrees  [Au-P = 2.2723 (14) A
      and Au-I = 2.5626 (6) A].

PMID- 22590186
TI  - Dimeth-yl(3-oxo-3-phenyl-prop-yl)aza-nium tetra-chloridoferrate(III).
AB  - In the title mol-ecular salt, (C(11)H(16)NO)[FeCl(4)], an intra-molecular N-H?O
      hydrogen bond in the cation generates an S(6) loop and the conformation of the
      C(=O)-C-C-N chain is gauche [torsion angle = 57.0 (6) degrees ]. The anion is a
      near-regular tetra-hedron [range of Cl-Fe-Cl angles = 107.93 (8)-112.13 (10)
      degrees ]. There are no directional inter-ionic bonds in the crystal.

PMID- 22590187
TI  - Dichloridobis[2-(1-hydrazinylideneeth-yl)pyrazine-kappaN(1)]zinc.
AB  - In the structure of the title complex, [ZnCl(2)(C(6)H(8)N(4))(2)], the Zn(II)
      atom has a distorted octa-hedral geometry. Two cis Cl(-) ions and four N atoms
      belonging to two different 2-(1-hydrazinylideneeth-yl)pyrazine ligands coordinate
      the Zn(II) atom, forming two five-membered Zn-N-C-C-N rings. The dihedral angle
      between the planes of these metallocycles is 88.13 (4) degrees . The organic
      ligands are essentially planar (r.m.s. deviations from planarity = 0.072 and
      0.040 A). Inter-molecular N-H?N and N-H?Cl inter-actions join the mol-ecules into
      a three-dimensional framework.

PMID- 22590188
TI  - (E)-Methyl 2-benzyl-3-o-tolyl-acrylate.
AB  - In the title compound, C(18)H(18)O(2), the methyl acrylate substituent adopts an
      extended E conformation with all torsion angles close to 180 degrees . The mean
      plane of the acrylate unit and the phenyl ring are approximately orthogonal to
      each other, making a dihedral angle of 81.40 (6) degrees . The position of the
      carbonyl group with respect to the olefinic double bond is typically S-trans. The
      crystal packing is stabilized by inter-molecular C-H?pi inter-actions.

PMID- 22590189
TI  - 5-[4-(1H-Imidazol-1-yl)phen-yl]-1H-tetra-zole.
AB  - In the title compound, C(10)H(8)N(6), the tetra-zole and benzene rings are close
      to being coplanar [dihedral angle = 9.90 (16) degrees ], but the imidazole ring
      is rotated 37.18 (09) degrees  out of the benzene plane. In the crystal, mol
      ecules are connected through tetra-zole-imidazole N-H?N hydrogen bonds, giving
      rise to zigzag chains, which extend along [010].

PMID- 22590190
TI  - N-p-Tolyl-pyrrolidine-1-carboxamide.
AB  - In the title mol-ecule, C(12)H(16)N(2)O, the pyrrolidine ring has a half-chair
      conformation. In the crystal, mol-ecules are linked into C(4) chains along [001]
      by N-H?O hydrogen bonds.

PMID- 22590191
TI  - 1-Octyl-1H-benzimidazol-2(3H)-one.
AB  - In the title compound, C(15)H(22)N(2)O, the octyl group adopts an all-trans
      conformation. In the crystal, mol-ecules form centrosymmetric dimers with an R(2)
      (2)(8) graph-set motif, linked by pairs of N-H?O hydrogen bonds. In addition, C
      H?O contacts are observed.

PMID- 22590192
TI  - (Z)-4-[(Ethyl-amino)(furan-2-yl)methyl-idene]-3-methyl-1-phenyl-1H-pyrazol-5(4H)
      one.
AB  - In the crystal of the title compound, C(17)H(17)N(3)O(2), the mol-ecules exist in
      the keto-enamine form. The pyrazole ring is oriented at 10.59 (4) and 57.98 (5)
      degrees  to the phenyl and furyl rings, respectively, and the dihedral angle
      between phenyl and furyl rings is 73.30 (11) degrees . An intra-molecular N-H?O
      hydrogen bond occurs between imino and carbonyl groups. In the crystal, weak C
      H?O hydrogen bonds link the mol-ecules into supra-molecular chains along the b
      axis.

PMID- 22590193
TI  - 3-[(8-But-oxy-quinolin-2-yl)meth-yl]-1-(pyridin-2-ylmeth-yl)-1H-imidazol-3-ium
      hexa-fluoridophosphate.
AB  - In the cation of the title compound, C(23)H(25)N(4)O(+).PF(6) (-), the
      imidazolium ring make dihedral angles of 87.20 (6) and 79.89 (5) degrees  with
      the pyridine ring and the quinoline system, respectively. In the crystal, C-H?F
      and C-H?N hydrogen bonds are observed.

PMID- 22590194
TI  - 5-(Thio-phen-2-ylmeth-yl)-1,3,4-thia-diazol-2-amine.
AB  - In the title mol-ecule, C(7)H(7)N(3)S(2), the dihedral angle between the thio
      phene and thia-diazole rings is 72.99 (5) degrees ; the two rings are oriented so
      that the S atoms in each ring are on the same side. In the crystal, the three
      dimensional network involves strong N-H?O hydrogen bonds, as well as C-H?pi and
      pi-pi stacking inter-actions [centroid-centroid distances = 3.654 (1) and 3.495
      (1) A].

PMID- 22590195
TI  - 3-Methyl-1-phenyl-4-[(phen-yl)(2-phenyl-hydrazin-1-yl)meth-ylidene]-1H-pyrazol
      5(4H)-one.
AB  - The title compound, C(23)H(20)N(4)O, is a heterocyclic phenyl-hydrazone Schiff
      base with a pyrazole moiety. In the crystal, a variety of inter-actions occur,
      including N-H?pi and pi-pi stacking between the phenyl ring of the phenyl
      hydrazinyl group and its symmetry-generated equivalent [centroid-centroid
      distance = 3.6512 (7) A].

PMID- 22590196
TI  - 3,3'-(1,4-Phenyl-ene)bis-[2-(propyl-amino)-benzofuro[3,2-d]pyrimidin-4(3H)-one]
      ethanol disolvate.
AB  - The title compound, C(32)H(28)N(6)O(4).2C(2)H(5)OH, consists of two 2-(propyl
      amino)-benzofuro[3,2-d]pyrimidin-4(3H)-one units connected, via one of the
      pyrimidine N atoms, to a bridging benzene ring in the 1,4 positions. Two ethanol
      solvent mol-ecules are also present. The main mol-ecule lies on a center of
      symmetry located at the center of the benzene ring. The fused-ring system of the
      benzofuro[3,2-d]pyrimidine moiety is nearly planar (r.m.s. deviation = 0.016 A)
      and forms a dihedral angle of 78.21 (7) degrees  with the central benzene ring.
      The crystal structure features O-H?O and N-H?O inter-actions. The C atoms of the
      propyl-amino side chain in the main mol-ecule and the ethyl group in the solvent
      mol-ecule are disordered over two positions, with site-occupancy factors
      0.34:0.66 and 0.42:0.58, respectively.

PMID- 22590197
TI  - 6,7,8,14,15,16-Hexaphenyldibenzo[c,gh]naphtho[3,2,1,8-pqra]tetraphene-5,13-dione
      dichloromethane monosolvate.
AB  - The main mol-ecule of the title compound, C(66)H(38)O(2).CH(2)Cl(2), is
      centrosymmetric, the asymmetric unit is composed of two half-mol-ecules, located
      on inversion centers, and a mol-ecule of dichloro-methane. The large pi
      conjugated fused polycyclic system including eight six-membered rings is nearly
      planar, with r.m.s. deviations of 0.2114 and 0.2081 A in the two independent mol
      ecules.

PMID- 22590198
TI  - Creatininium 2-chloro-acetate.
AB  - IN THE TITLE COMPOUND (SYSTEMATIC NAME: 2-amino-1-methyl-4-oxo-4,5-dihydro-1H
      imidazol-3-ium 2-chloro-acetate), C(4)H(8)N(3)O(+).C(2)H(2)ClO(2) (-), the mol
      ecular aggregations are stabil-ized through classical (N-H?O) and non-classical
      (C-H?O and C-H?N) hydrogen-bonding inter-actions. The cations are linked to the
      anions, forming ion pairs through two N-H?O bonds that produce characteristic
      R(2) (2)(8) ring motifs. These cation-anion pairs are connected through another N
      H?O hydrogen bond, leading to an R(4) (2)(8) ring motif. Further weak C-H?N inter
      actions link the mol-ecules along the a axis, while other C-H?O inter-actions
      generate zigzag chains extending along b.

PMID- 22590199
TI  - N-(2,6-Dimethyl-phen-yl)-2,2-diphenyl-acetamide.
AB  - In the title compound, C(22)H(21)NO, the dihedral angle between the phenyl rings
      is 82.59 (7) degrees . The dimethyl-benzene ring forms dihedral angles of 52.86
      (4) and 49.65 (5) degrees  with the two phenyl rings. In the crystal, mol-ecules
      are linked by N-H?O hydrogen bonds, forming a C(4) chain along the c axis. The
      crystal also features C-H?pi inter-actions.

PMID- 22590200
TI  - Diethyl 4-[5-(4-chloro-phen-yl)-1H-pyrazol-4-yl]-2,6-dimethyl-1,4-dihydro
      pyridine-3,5-dicarboxyl-ate.
AB  - In the title compound, C(22)H(24)ClN(3)O(4), intra-molecular C-H?O and C-H?N
      hydrogen bonds form S(9) and S(7) ring motifs, respectively. The 1,4-dihydro
      pyridine ring adopts a flattened boat conformation. The benzene ring makes a
      dihedral angle of 33.36 (6) degrees  with the pyrazole ring. In the crystal,
      pairs of N-H?N hydrogen bonds link the mol-ecules into inversion dimers. The
      dimers are stacked in column along the a axis through N-H?O and C-H?N hydrogen
      bonds. The crystal packing also features C-H?pi inter-actions involving the
      pyrazole ring.

PMID- 22590201
TI  - 1,3-Dimethyl-1H-indazol-6-amine.
AB  - The mol-ecular skeleton of the title compound, C(9)H(11)N(3), is almost planar,
      with a maximum deviation of 0.0325 (19) A for the amino N atom. In the crystal, N
      H?N hydrogen bonds establish the packing.

PMID- 22590202
TI  - 3,4-Dimeth-oxy-4'-nitro-1,1'-biphen-yl.
AB  - The title compound, C(14)H(13)NO(4), was prepared through a palladium-catalysed
      Suzuki-Miyaura coupling reaction. The asymmetric unit comprises two mol-ecules
      related by pseudo-inversion symmetry. The dihedral angles between the benzene
      rings in the two mol-ecules are 44.30 (6) and 48.50 (6) degrees  while those
      between the benzene ring and the nitro group are 6.54 (13) and 5.73 (10) degrees
      . The crystal packing is defined only by Van der Waals inter-actions.

PMID- 22590203
TI  - 1-(4,5,6,7-Tetra-hydro-thieno[3,2-c]pyridin-5-yl)-2-{4-[3-(trifluoro-meth-yl)phen
      yl]piperazin-1-yl}ethanone.
AB  - In the title mol-ecule, C(20)H(22)F(3)N(3)OS, the piperazine ring has a chair
      conformation, and the N-C(=O)-C-N torsion angle is -59.42 (14) degrees . In the
      crystal, weak C-H?O and C-H?pi inter-actions link the mol-ecules into layers
      parallel to (101).

PMID- 22590204
TI  - 6-Chloro-N(4),N(4)-dimethyl-pyrimidine-2,4-diamine.
AB  - The asymmetric unit of the title compound, C(6)H(9)ClN(4), contains four
      independent mol-ecules (A, B, C and D). Their main difference is the torsion
      angles, ranging from 1.6 (5) to 5.9 (5) degrees , between the methyl group and
      the pyrimidine plane. A pair of inter-molecular N-H?N hydrogen bonds link mol
      ecules A and C into a twisted dimer with a dihedral angle of 32.9 (1) degrees 
      between the two pyrimidine rings, creating an R(2) (2)(8) motif. In the packing,
      each two mol-ecules of B, C and D form centrosymmetric dimers through two inter
      molecular N-H?N hydrogen bonds, locally creating R(2) (2)(8) motifs. The dimers
      of C and D are alternately bridged by A into an infinite zigzag strip, locally
      creating two different R(2) (2)(8) motifs with dihedral angles of 32.9 (1) and
      63.4 (1) degrees  between the pyrimidine rings. Finally, these strips together
      with the dimers of B associate into a complicated three-dimensional framework.

PMID- 22590205
TI  - 1'-Methyl-4'-[4-(trifluoro-meth-yl)phen-yl]dispiro-[acenaphthyl-ene-1,2'
      pyrrolidine-3',2''-indane]-2,1''(1H)-dione.
AB  - In the title compound, C(31)H(22)F(3)NO(2), the pyrrolidine and cyclo-pentane
      rings within the dihydro-indene ring system are in envelope conformations, with
      the N atom and the spiro-C atom at the flap, respectively. An intra-molecular C
      H?O hydrogen bond forms an S(8) ring motif. The mean plane through the
      pyrrolidine ring [r.m.s. deviation = 0.179 (2) A] makes dihedral angles of 86.30
      (13), 88.99 (10) and 79.69 (11) degrees  with the benzene ring, the dihydro
      acenaphthyl-ene ring and the mean plane of the indane system, respectively. In
      the crystal, mol-ecules are linked by C-H?O and C-H?N hydrogen bonds into a two
      dimensional network parallel to the ac plane. C-H?pi inter-actions further
      stabilize the crystal structure.

PMID- 22590206
TI  - 5-Bromo-2-methyl-3-(4-methyl-phenyl-sulfin-yl)-1-benzofuran.
AB  - In the title compound, C(16)H(13)BrO(2)S, the 4-methyl-phenyl ring makes a
      dihedral angle of 87.83 (6) degrees  with the mean plane [mean deviation = 0.007
      (1) A] of the benzofuran fragment. In the crystal, mol-ecules are linked by weak
      C-H?O hydrogen bonds and Br?O contacts [3.099 (2) A]. The crystal structure also
      exhibits pi-pi inter-actions between the furan and benzene rings of neighbouring
      mol-ecules [centroid-centroid distance = 3.637 (2) A, inter-planar distance =
      3.317 (2) A and slippage = 1.492 (2) A].

PMID- 22590207
TI  - N'-Cyclo-pentyl-idene-pyridine-4-carbo-hydrazide.
AB  - The title compound, C(11)H(13)N(3)O, is a derivative of the anti-tuberculosis
      drug isoniazid [systematic name: pyridine-4-carbohydrazide]. The crystal
      structure consists of repeating hydrogen-bonded chains parallel to the b axis.
      Adjacent mol-ecules in the chains are linked by bifurcated N-H?(O,N) hydrogen
      bonds, which form an R(1) (2)(5) ring motif.

PMID- 22590208
TI  - 4-(4-Chloro-phen-yl)-2,6-bis-(1H-indol-3-yl)-1,4-dihydro-pyridine-3,5-dicarbo
      nitrile ethanol monosolvate.
AB  - In the title compound, C(29)H(18)ClN(5).C(2)H(6)O, the dihydro-pyridine ring
      adopts a strongly flattened envelope conformation, with a maximum deviation of
      0.139 (2) A from its best plane for the Csp(3) atom. The dihedral angles between
      the dihydro-pyridine ring plane and the two indole rings in positions 2 and 6 are
      34.28 (5) and 40.50 (6) degrees , respectively. In turn, the benzene ring and the
      dihydro-pyridine ring are oriented at a dihedral angle of 74.69 (6) degrees . An
      intra-molecular C-H?Cl hydrogen bond occurs. In the crystal, mol-ecules are
      linked by N-H?N, N-H?O and O-H?N hydrogen bonds into layers parallel to (001).
      There are short C-H?Cl contacts between mol-ecules in neighboring layers.

PMID- 22590209
TI  - 4,4-Difluoro-8-(4-iodo-phen-yl)-1,3,5,7-tetra-methyl-3a-aza-4a-azonia-4-borata-s
      indacene.
AB  - In the title compound, C(19)H(18)BF(2)IN(2), which is a boron-dipyrromethene
      (BODIPY) derivative, the BODIPY mean plane forms dihedral angles of 88.95 (4) and
      78.21 (3) degrees  with the F/B/F and 4-iodo-phenyl planes, respectively.

PMID- 22590210
TI  - 2-[(3-Bromo-anilino)meth-yl]-1,2-benzo-thia-zol-3(2H)-one.
AB  - The title compound, C(14)H(11)BrN(2)OS, was synthesized by the reaction of 1,2
      benzothia-zol-3(2H)-one with formalin and 3-bromo-aniline in ethanol. The 1,2
      benzothia-zolone ring system is approximately planar [maximum deviation = 0.0142
      (s.u.?) A] and forms a dihedral angle of 79.19 (5) degrees  with the benzene
      ring. In the crystal, molecules are linked by N-H?O, C-H?O and C-H?Br
      interactions.

PMID- 22590211
TI  - (E)-N'-(5-Bromo-2-hy-droxy-benzyl-idene)-4-(dimethyl-amino)-benzohydrazide.
AB  - The title compound, C(16)H(16)BrN(3)O(2), crystallized with two independent
      molcules in the asymmetric unit. Each mol-ecule has an E conformation about the
      C=N bond and the dihedral angles between the benzene rings are 30.5 (3) and 28.7
      (3) degrees . In each mol-ecule, there is an O-H?N hydrogen bond and the two mol
      ecules are linked by an N-H?O hydrogen bond. In the crystal, mol-ecules are
      further linked via N-H?O hydrogen bonds into chains propagating along [001].

PMID- 22590212
TI  - 2-{4-[Acet-yl(eth-yl)amino]-benzene-sulfonamido}-benzoic acid.
AB  - In the title compound, C(17)H(18)N(2)O(5)S, the dihedral angle between the
      aromatic rings is 68.59 (10) degrees  and the C-S-N-C torsion angle is -81.84
      (18) degrees . The mol-ecular conformation is stabilized by an intra-molecular N
      H?O hydrogen bond, generating an S(6) ring. In the crystal, mol-ecules are linked
      by C-H?O and O-H?O hydrogen bonds into a three-dimensional network.

PMID- 22590213
TI  - 2,3-Dihydro-1lambda(6),2-benzothia-zine-1,1,4-trione.
AB  - In the title compound, C(8)H(7)NO(3)S, the benzene ring is oriented at a dihedral
      angle of 69.25 (7) degrees  to the S and O atoms of the sulfonyl group. The
      heterocyclic ring approximates to an envelope, with the N atom in the flap
      position. In the crystal, mol-ecules are linked by N-H?O(c) (c = carbon-yl)
      hydrogen bonds, forming C(5) chains along [001]. Two R(2) (2)(10) loops arise
      from pairs of C-H?O hydrogen bonds and a weak aromatic pi-pi stacking inter
      action [centroid-centorid separation = 3.8404 (11) A] also occurs.

PMID- 22590214
TI  - Hydrogen bonding in 1-carb-oxy-propanaminium nitrate.
AB  - There are two crystallographically independent cations and two anions in the
      asymmetric unit of the title compound, C(4)H(5)NO(2) (+).NO(3) (-). In the
      crystal, the 1-carb-oxy-propanaminium cations and nitrate anions are linked to
      each other through strong N-H?O and O-H?O hydrogen bonds, forming a three
      dimensional complex network. C-H?O inter-actions also occur.

PMID- 22590215
TI  - 10alpha-Hy-droxy-13-{[4-(2-hy-droxy-phen-yl)piperazin-1-yl]meth-yl}-4,9-dimethyl
      3,8,15-trioxatetra-cyclo-[10.3.0.0(2,4).0(7,9)]penta-decan-14-one.
AB  - The title compound, C(25)H(34)N(2)O(6), was synthesized from 9alpha-hy-droxy
      parthenolide (9alpha-hy-droxy-4,8-dimethyl-12-methyl-ene-3,14-dioxatricyclo
      [9.3.0.0(2,4)]tetra-dec-7-en-13-one), which was isolated from the chloro-form
      extract of the aerial parts of Anvillea radiata. The ten-membered ring adopts an
      approximate chair-chair conformation, while the piperazine ring displays a near
      regular chair conformation and the five-membered ring an envelope conformation
      with the C atom closest to the hy-droxy group forming the flap. The mol-ecular
      conformation is stabilized by an O-H?N hydrogen bond, which generates an S(7)
      loop, and the crystal structure features weak C-H?O inter-actions.

PMID- 22590216
TI  - (2E,4E)-2-Cyano-5-dipropyl-amino-N,N-dimethyl-penta-2,4-dienamide.
AB  - In the title compound, C(14)H(23)N(3)O, the n-propyl group is disordered over two
      orientations with an occupancy ratio of 0.778 (3):0.222 (3). In the crystal, mol
      ecules are linked by pairs of weak C-H?O inter-actions into inversion dimers with
      an R(2) (2)(14) graph-set motif.

PMID- 22590217
TI  - 2,2-Diphenyl-N-(1,3-thia-zol-2-yl)acetamide.
AB  - In the title mol-ecule, C(17)H(14)N(2)OS, the mean plane of the acetamide group
      forms dihedral angles of 75.79 (5), 81.85 (6) and 12.32 (5) degrees  with the two
      phenyl rings and the thia-zole ring, respectively. In the crystal, N-H?N hydrogen
      bonds link pairs of mol-ecules into inversion dimers with R(2) (2)(8) ring
      motifs. The crystal packing is further stabilized by C-H?pi inter-actions and by
      pi-pi inter-actions with a centroid-centroid distance of 3.6977 (5) A.

PMID- 22590218
TI  - (2E)-3-(2-Bromo-phen-yl)-1-(4,4''-difluoro-5'-meth-oxy-1,1':3',1''-terphenyl-4'
      yl)prop-2-en-1-one.
AB  - In the title compound, C(28)H(19)BrF(2)O(2), the central benzene ring makes
      dihedral angles of 62.51 (18), 46.23 (18) and 48.19 (18) degrees  with the bromo
      substituted benzene ring and two terminal fluoro-substituted benzene rings,
      respectively. In the crystal, mol-ecules are linked by C-H?F hydrogen bonds into
      infinite chains along [110]. Weak C-H?pi and pi-pi inter-actions [centroid
      centroid distance = 3.683 (2) A] also occur and short inter-molecular F?F
      contacts [2.833 (4) A] are observed.

PMID- 22590219
TI  - N-(2,4-Dimethyl-phen-yl)-2,2-diphenyl-acetamide.
AB  - The asymmetric unit of the title compound, C(22)H(21)NO, consists of two
      crystallographically independent mol-ecules (A and B). Each mol-ecule contains
      two benzene rings and one dimethyl-benzene ring. The dihedral angle between the
      two benzene rings is 87.75 (16) degrees  in mol-ecule A and 89.25 (16) degrees 
      in mol-ecule B. In mol-ecule A, the dimethyl-benzene ring forms dihedral angles
      of 89.65 (8) and 42.98 (11) degrees  with the two benzene rings, whereas the
      corresponding angles are equal to 63.15 (7) and 58.67 (10) degrees  in mol-ecule
      B. An intra-molecular C-H?O hydrogen bond generates an S(6) ring motif in each
      mol-ecule. In the crystal, mol-ecules are linked by bifurcated (N,C)-H?O hydrogen
      bonds, generating R(2) (1)(6) ring motifs and forming infinite chains along the a
      axis. The crystal is further stabilized by C-H?pi and pi-pi inter-actions with
      centroid-centroid distances of 3.8543 (18) and 3.930 (2) A.

PMID- 22590220
TI  - Oxyresveratrol from Mulberry as a dihydrate.
AB  - The title compound {systematic name: 4-[(E)-2-(3,5-dihy-droxy-phen-yl)ethen
      yl]benzene-1,3-diol dihydrate}, C(14)H(12)O(4).2H(2)O, a derivative of
      resveratrol, was isolated from mulberry. The linking C=C double bond has a trans
      conformation and allows the formation of a conjugated system throughout the mol
      ecule. The dihedral angle between the benzene rings is 9.39 (9) degrees . In the
      crystal, mol-ecules are connected into a three-dimensional architecture through O
      H?O hydrogen bonds between hy-droxy groups of oxyresveratrol and solvent water
      mol-ecules.

PMID- 22590221
TI  - (E)-4-Amino-N'-(3-nitro-benzyl-idene)benzohydrazide.
AB  - In the title compound, C(14)H(12)N(4)O(3), the dihedral angle between the benzene
      rings is 7.6 (4) degrees . In the crystal, infinite sheets linked by N-H?O and
      bifurcated N-H?(O,N) hydrogen bonds propagate in the (10-1) plane, in which R(4)
      (4)(36) loops are apparent. Neighbouring layers may inter-act by way of very weak
      pi-pi stacking inter-actions [centroid-centroid distances = 3.9329 (13) and
      4.0702 (13) A].

PMID- 22590222
TI  - 2,2'-(Ethane-1,2-di-yl)bis-(1H-benzimidazole).
AB  - The complete mol-ecule of the title compound, C(16)H(14)N(4), is generated by
      crystallographic inversion symmetry. In the crystal, mol-ecules are linked by N
      H?N hydrogen bonds, generating (001) sheets. Weak aromatic pi-pi stacking inter
      actions [centroid-centroid distances = 3.7383 (13) and 3.7935 (14) A] are also
      observed.

PMID- 22590223
TI  - 4-(3-Carb-oxy-phen-yl)pyridinium nitrate.
AB  - In the title salt, C(12)H(10)NO(2) (+).NO(3) (-), the dihedral angle between the
      pyridine ring and the benzene ring of the 4-(3-carb-oxy-phen-yl)pyridinium cation
      is 30.14 (2) degrees . Inversion-related pairs of cations are linked into dimers
      by pairs of O-H?O hydrogen bonds. Pairs of dimers are linked by N-H?O and C-H?O
      hydrogen bonds involving nitrate anions as acceptors, generating supra-molecular
      chains along the diagonal of the bc plane.

PMID- 22590224
TI  - Resorcinol ninhydrin complex: 1,5,9-trihy-droxy-8-oxatetra-cyclo
      [7.7.0.0(2,7).0(10,15)]hexa-deca-2,4,6,10(15),11,13-hexaen-16-one.
AB  - In the title compound, C(15)H(10)O(5), the cyclo-penta-none (r.m.s. deviation =
      0.049 A) and oxolane (r.m.s. deviation = 0.048 A) rings make a dihedral angle of
      67.91 (4) degrees . An intra-molecular O-H?O hydrogen bond is observed. In the
      crystal, mol-ecules associate via O-H?O hydrogen bonds, forming a three
      dimensional network.

PMID- 22590225
TI  - 4-[(4-Benzyl-oxybenzyl-idene)amino]-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one.
AB  - In the title mol-ecule, C(25)H(23)N(3)O(2), two terminal phenyl rings are twisted
      by 50.20 (6) and 71.26 (5) degrees  from the mean plane (r.m.s. deviation = 0.032
      A) of the central benzyl-idene-amino-pyrazolone fragment. The N atoms of the
      pyrazole ring have a pyramidal environment, the sums of the valence angles around
      them being 353.5 (2) and 347.3 (2) degrees . The crystal structure is stabilized
      by C-H?O interactions.

PMID- 22590226
TI  - Diethyl 4-meth-oxyoxalyl-3,5-diphenyl-pyrrolidine-2,2-dicarboxyl-ate.
AB  - In the title compound, C(25)H(27)NO(7), the pyrrolidine ring exhibits an envelope
      conformation and the benzene rings form a dihedral angle of 33.47 (11) degrees .
      In the crystal, pairs of N-H?O hydrogen bonds link the mol-ecules into
      centrosymmetric dimers. Weak C-H?O inter-actions link the dimers into layers
      parallel to the bc plane.

PMID- 22590227
TI  - (2-Chloro-phen-yl)(4-hy-droxy-1,1-dioxo-2H-1,2-benzothia-zin-3-yl)methanone.
AB  - In the title mol-ecule, C(15)H(10)ClNO(4)S, the heterocyclic thia-zine ring
      adopts a half-chair conformation, with the S and N atoms displaced by 0.527 (7)
      and 0.216 (7) A, respectively, on opposite sides of the mean plane formed by the
      remaining ring atoms. The mol-ecular structure is consolidated by an intra
      molecular O-H?O inter-action and the crystal packing is stabilized by N-H?O and C
      H?O hydrogen bonds.

PMID- 22590228
TI  - N-(3-Methyl-benzo-yl)benzene-sulfonamide.
AB  - The asymmetric unit of the title compound, C(14)H(13)NO(3)S, contains three
      independent mol-ecules in which the dihedral angles between the sulfonyl and
      benzoyl benzene rings are 83.3 (2), 84.4 (2) and 87.6 (2) degrees . In the
      crystal, mol-ecules are linked into chains running along the a axis via N-H?O
      hydrogen bonds.

PMID- 22590229
TI  - 3,4-Bis(4-meth-oxy-phen-yl)-2,5-dihydro-1H-pyrrole-2,5-dione.
AB  - In the title compound, C(18)H(15)NO(4), the benzene rings form quite different
      dihedral angles [16.07 (1) and 59.50 (1) degrees ] with the central pyrrole ring,
      indicating a twisted mol-ecule. Conjugation is indicated between the five- and
      six-membered rings by the lengths of the C-C bonds which link them [1.462 (3) and
      1.477 (3) A]. The most prominent feature of the crystal packing is the formation
      of inversion dimers via eight-membered {?HNCO}(2) synthons.

PMID- 22590230
TI  - rac-7,7',9,9'-Tetra-phenyl-9a,9a'-bi(7,8,9,9a-tetra-hydro-6aH-penta-leno[1,2,3
      ij]naphthalen-8-one).
AB  - The racemic title compound, C(54)H(38)O(2), consists of two C-linked penta
      leno[1,2,3-ij]naphthalenone moieties, the crowded aryl ring substitution on the
      cyclo-pentane rings forcing the two segments to assume a conformation which has
      pseudo-twofold rotational symmetry, with a dihedral angle between the naphthalene
      substituent groups of 55.30 (8) degrees . In each segment, the two phenyl rings
      have different conformational orientations, with inter-ring dihedral angles of
      34.7 (2) and 49.63 (16) degrees . Each cyclo-pentane ring has the same relative
      configuration in its four chiral centres and together with the fused naphthalene
      ring assumes an overall chair-like conformation.

PMID- 22590231
TI  - 2-(5-Amino-2H-tetra-zol-2-yl)acetic acid.
AB  - In the title mol-ecule, C(3)H(5)N(5)O(2), the tetra-zole ring and carboxyl group
      form a dihedral angle of 82.25 (14) degrees . In the crystal, adjacent mol-ecules
      are linked through O-H?N, N-H?O and N-H?N hydrogen bonds into layers parallel to
      the bc plane.

PMID- 22590232
TI  - The pseudosymmetric structure of bis-(pentane-1,5-diaminium) iodide tris
      (triiodide).
AB  - The asymmetric unit of the title compound, [H(3)N(CH(2))(5)NH(3)](2)I[I(3)](3) or
      2C(5)H(16)N(2) (2+).3I(3) (-).I(-), consists of two crystallographically
      independent pentane-1,5-diaminium dications and two triiodide anions in general
      positions besides two additional triiodide and two iodide anions located on
      twofold axes. The compound crystallizes in the centrosymmetric monoclinic space
      group P2/n. The structure refinement was handicapped by the pseudosymmetry
      (pseudo-centering) of the structure and by twinning. The crystal structure is
      composed of two alternate layers, which differ in their arrangement of the
      pentane-1,5-diaminium dications and the iodide/triiodide anions and which are
      connected via weak to medium-strong N-H?I hydrogen bonds, constructing a complex
      hydrogen-bonded network.

PMID- 22590233
TI  - Bis(5-amino-3-carb-oxy-1H-1,2,4-triazol-4-ium) dihydrogenphosphate nitrate 5
      amino-1H-1,2,4-triazol-4-ium-3-carboxyl-ate.
AB  - In the title compound, 2C(3)H(5)N(4)O(2) (+).H(2)PO(4) (-).NO(3) (
      ).C(3)H(4)N(4)O(2), three independent 5-amino-1H-1,2,4-triazol-3-carb-oxy-lic
      acid moieties are observed. Two are in the form of cations, while the third is in
      the zwitterionic form. The triazole rings in the two cations are almost coplanar,
      making an angle of 4.11 (7) degrees . Layers parallel to the (20-1) plane,
      resulting from hydrogen bonding of the organic mol-ecules and the nitrate anions,
      are linked via H(2)PO(4) (-) infinite zigzag chains running parallel to the c
      axis. The crystal studied was an inversion twin, with refined components of 0.33
      (7) and 0.67 (7).

PMID- 22590234
TI  - (E)-2-Bromo-4-[(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)imino
      meth-yl]-6-meth-oxy-phenyl 4-methyl-benzene-sulfonate.
AB  - In the title compound, C(26)H(24)BrN(3)O(5)S, the central benzene ring makes
      dihedral angles of 6.27 (6), 33.63 (6) and 69.31 (5) degrees , respectively, with
      the pyrazolone ring, the bromo-benzene ring and the terminal phenyl ring. An
      intra-molecular C-H?O hydrogen bond occurs. The crystal packing features weak non
      classical C-Br?O inter-actions [Br?O = 3.222 (2) A] that form inversion-related
      dimers.

PMID- 22590235
TI  - N'-(3-Bromo-5-chloro-2-hy-droxy-benzyl-idene)-2H-1,3-benzodioxole-5-carbo
      hydrazide.
AB  - The asymmetric unit of the title hydrazone compound, C(15)H(10)BrClN(2)O(4),
      contains two independent mol-ecules. The dihedral angles between the benzene
      rings are 38.7 (3) degrees  in one mol-ecule and 24.3 (3) degrees  in the other.
      Both mol-ecules exist in trans conformations with respect to the C=N double bonds
      of the central methyl-idene units. Intra-molecular O-H?N contacts are observed in
      both mol-ecules, forming S(6) rings. In the crystal, mol-ecules are linked
      through N-H?O hydrogen bonds into chains along the a axis.

PMID- 22590236
TI  - N'-(3-Fluoro-benzyl-idene)-4-hy-droxy-3-meth-oxy-benzohydrazide methanol
      monosolvate.
AB  - In the title compound, C(15)H(13)FN(2)O(3).CH(3)OH, the dihedral angle between
      the benzene rings of the benzohydrazone mol-ecule is 5.3 (3) degrees . The C atom
      of the meth-oxy group is almost coplanar with its attached ring [deviation =
      0.017 (2) A]. The r.m.s. deviation of the 21 non-H atoms of the hydrazone mol
      ecule is 0.106 A. In the crystal, the components are linked by O(m)-H?O(h), N(h)
      H?O(m) and O(h)-H?O(h) (m = methanol and h = hydrazone) hydrogen bonds, forming
      (001) layers.

PMID- 22590237
TI  - 2,3,6,7-Tetra-bromo-9-butyl-9H-carbazole.
AB  - In he title compound, C(16)H(13)Br(4)N, the carbazole skeleton is nearly planar
      [maximum deviation = 0.026 (4) A] and makes a dihedral angle of 73.8 (4) degrees 
      with the butyl chain. The butyl chain adopts a trans conformation. In the
      crystal, mol-ecules are linked by pi-pi stacking inter-actions [centroid-centroid
      distance = 3.559 (2) A].

PMID- 22590238
TI  - 4'-(4-Bromo-phen-yl)-1'-methyl-dispiro-[acenaphthyl-ene-1,2'-pyrrolidine-3',2''
      indane]-2,1''(1H)-dione.
AB  - In the title compound, C(30)H(22)BrNO(2), the cyclo-pentane ring of the dihydro
      acenaphthyl-ene group and the pyrrolidine ring are both in envelope conformations
      with the spiro C atom and N atom, respectively, as the flap atom. The cyclo
      pentane ring of the indane group adopts a half-chair conformation. A weak intra
      molecular C-H?O hydrogen bond forms an S(8) ring motif. The naphthalene ring
      system of the dihydro-acenaphthyl-ene group forms dihedral angles of 41.76 (6)
      and 42.17 (6) degrees  with the benzene ring of the bromo-phenyl group and the
      benzene ring of the indane group, respectively. The dihedral angle between the
      two benzene rings is 83.92 (7) degrees . In the crystal, mol-ecules are linked by
      weak C-H?O and C-H?N hydrogen bonds into a two-dimensional network parallel to
      the ac plane. Weak C-H?pi inter-actions are also observed.

PMID- 22590239
TI  - 2-(Ethyl-sulfin-yl)imidazo[1,2-a]pyridine-3-sulfonamide.
AB  - The supra-molecular structure of the title compound, C(9)H(11)N(3)O(3)S(2), is
      defined by two inter-molecular hydrogen bonds. Pairs of N-H?N hydrogen bonds link
      the mol-ecules into centrosymmetric dimers and N-H?O hydrogen bonds link the
      dimers into a tubular chain structure running parallel to the a axis.

PMID- 22590240
TI  - N-[4-(Dimethyl-amino)-benzyl-idene]-4H-1,2,4-triazol-4-amine.
AB  - The title compound, C(11)H(13)N(5), is a Schiff base synthesized by the reaction
      of 4-amino-4H-1,2,4-triazole and 4-(dimethyl-amino)-benzaldehyde. The dihedral
      angle between the benzene and triazole rings is 43.09 (11) degrees . The crystal
      structure displays weak C-H?N inter-actions.

PMID- 22590241
TI  - 1-(4-Chloro-phen-yl)-1H-1,2,3,4-tetra-zole.
AB  - There are two independent mol-ecules in the asymmetric unit of the title
      compound, C(7)H(5)ClN(4), in which the tetra-zole and benzene rings are twisted
      by dihedral angles of 12.9 (1) and 39.8 (1) degrees . In the crystal, the
      independent mol-ecules are connected into a tetra-mer by C-H?N hydrogen bonds,
      generating an R(4) (4)(12) graph-set motif.

PMID- 22590242
TI  - 3-[(N-Methyl-anilino)meth-yl]-5-(thio-phen-2-yl)-1,3,4-oxadiazole-2(3H)-thione.
AB  - In the title compound, C(14)H(13)N(3)OS(2), the thio-phene ring is disordered
      over two orientations by ca 180 degrees  about the C-C bond axis linking the ring
      to the rest of the mol-ecule, with a site-occupancy ratio of 0.651 (5):0.349 (5).
      The central 1,3,4-oxadiazole-2(3H)-thione ring forms dihedral angles of 9.2 (5),
      4.6 (11) and 47.70 (7) degrees  with the major and minor parts of the disordered
      thio-phene ring and the terminal phenyl ring, respectively. In the crystal, no
      significant inter-molecular hydrogen bonds are observed. The crystal packing is
      stabilized by pi-pi inter-actions [centroid-centroid distance = 3.589 (2) A].

PMID- 22590243
TI  - 3-(Adamantan-1-yl)-4-ethyl-1H-1,2,4-triazole-5(4H)-thione.
AB  - In the title compound, C(14)H(21)N(3)S, the 1,2,4-triazole ring is nearly planar,
      with a maximum deviation of 0.003 (4) A. In the crystal, mol-ecules are linked
      into inversion dimers by pairs of N-H?S hydrogen bonds.

PMID- 22590244
TI  - N-(3-Chloro-4-fluoro-phen-yl)acetamide.
AB  - In the title compound, C(8)H(7)ClFNO, the dihedral angle between the benzene ring
      and the acetamide side chain is 5.47 (6) degrees . An S(6) ring motif is formed
      via an intra-molecular C-H?O hydrogen bond. In the crystal, N-H?O hydrogen bonds
      link the mol-ecules into C(4) chains along [001].

PMID- 22590246
TI  - 2-Carb-oxy-6-(quinolin-1-ium-8-yl-oxy)benzoate.
AB  - In the zwitterionic title compound, C(17)H(11)NO(5), the dihedral angle between
      the two aromatic rings is 76.90 (7) degrees . The dihedral angles between the
      carboxyl groups and the benzene ring are 64.02 (9) and 21.67 (9) degrees , the
      larger angle being associated with an intra-molecular N-H?O(carbox-yl) hydrogen
      bond, resulting from proton transfer from the carb-oxy-lic acid group to the
      quinoline N atom and giving an S(9) ring motif. In the crystal, mol-ecules are
      connected by O-H?O hydrogen bonds into chains extending along the b-axis
      direction. An overall two-dimensional network structure is formed through pi-pi
      inter-actions between the quinoline rings [minimum ring-centroid separation =
      3.6068 (6) A].

PMID- 22590245
TI  - N-(3,4-Difluoro-phen-yl)-2,2-diphenyl-acetamide.
AB  - In the title compound, C(20)H(15)F(2)NO, the mean plane of the acetamide group
      makes dihedral angles of 88.26 (6), 78.30 (7) and 9.83 (6) degrees  with the two
      terminal benzene rings and difluoro-substituted benzene ring, respectively. One F
      atom is disordered over two orientations rotated by 180 degrees , with a site
      occupancy ratio of 0.557 (2):0.443 (2). An intra-molecular C-H?O hydrogen bond
      generates an S(6) ring motif. In the crystal, mol-ecules are linked via N-H?O
      hydrogen bonds into chains along the c axis. The crystal structure is further
      consolidated by C-H?pi inter-actions.

PMID- 22590247
TI  - 4-Hy-droxy-N'-(3-nitro-benzyl-idene)benzohydrazide.
AB  - The title compound, C(14)H(11)N(3)O(4), was obtained by a condensation reaction
      between 3-nitro-benzaldehyde and 4-hy-droxy-benzohydrazide. The whole mol-ecule
      is approximately planar, with a dihedral angle of 9.2 (3) degrees  between the
      benzene rings. The mol-ecule displays an E conformation about the C=N bond. In
      the crystal, mol-ecules are linked via N-H?O, O-H?O and O-H?N hydrogen bonds,
      generating sheets parallel to the bc plane.

PMID- 22590248
TI  - 5,17-Dibromo-26,28-bis-[(meth-oxy-carbon-yl)meth-oxy]-25,27-diprop-oxy-2,8,14,20
      tetra-thia-calix[4]arene.
AB  - The title thia-calix[4]arene derivative, C(36)H(34)Br(2)O(8)S(4), adopts an
      unusual pinched cone conformation with the prop-oxy-substituted benzene rings
      inclined inward [forming a dihedral angle of 33.4 (1) degrees ] and with the
      brominated benzene rings bent outward, making a dihedral angle of 66.1 (1)
      degrees . In the crystal, the mol-ecules form chains along [001] via C-H?S
      hydrogen bonds and S?S contacts [S?S = 3.492 (3) A]. The chains are associated
      into bilayers through C-H?O hydrogen bonds, generating an R(2) (2)(10) motif.

PMID- 22590249
TI  - N-(2-{[7-(2-Anilinoeth-oxy)-3,6-dibromo-naphthalen-2-yl]-oxy}eth-yl)aniline.
AB  - In the title compound, C(26)H(24)Br(2)N(2)O(2), the central naphthalene system
      carries two Br atoms and two -CH(2)CH(2)NHC(6)H(5) substituents. The phenyl rings
      of the latter residues are inclined at 74.17 (17) and 51.4 (2) degrees  with
      respect to the naphthalene ring system. Each alkyl chain adopts a fully extended
      all-cis conformation with respect to the naphthalene and phenyl rings [N-C-C-O
      torsion angles = 68.6 (4) and 60.5 (4) degrees ]. In the crystal, one of the N-H
      groups forms bifurcated N-H?(Br,O) hydrogen bonds, which link the mol-ecules into
      inversion-related dimers. The centrosymmetric dimers are aggregated via pairs of
      C-H?pi inter-actions into sheets parallel to (110).

PMID- 22590250
TI  - 2-{[5-(Adamantan-1-yl)-4-methyl-4H-1,2,4-triazol-3-yl]sulfan-yl}-N,N-dimethyl
      ethanamine.
AB  - In the title compound, C(17)H(28)N(4)S, the 1,2,4-triazole ring is nearly planar
      [maximum deviation = 0.005 (2) A]. There are no significant hydrogen bonds
      observed in the crystal structure. The crystal studied was a non-merohedral twin,
      the refined ratio of twin components being 0.281 (3):0.719 (3).

PMID- 22590251
TI  - Lurasidone hydro-chloride.
AB  - In the crystal structure of the title compound, C(28)H(37)N(4)O(2)S(+).Cl(-)
      [systematic name: 4-(1,2-benzothia-zol-3-yl)-1-({2-[(3,5-dioxo-4-aza-tricyclo
      [5.2.1.0(2,6)]decan-4-yl)meth-yl]cyclo-hex-yl}meth-yl)piperazin-1-ium chloride],
      the anions and cations are linked by N-H?Cl hydrogen bonds. The crystal structure
      is further stabilized by C-H?pi and C-H?O inter-actions.

PMID- 22590252
TI  - 4,4'-{[4-(2,2':6',2''-Terpyridin-4'-yl)phen-yl]imino}-dibenzaldehyde.
AB  - The central pyridine ring of the 2,2':6',2''-terpyridine fragment of the title
      compound, C(35)H(24)N(4)O(2), forms dihedral angles of 8.3 (2), 10.6 (3) and 39.4
      (3) degrees , respectively, with the two outer pyridine rings and the attached
      benzene ring. In the crystal, weak C-H?O inter-actions link the mol-ecules into
      chains in [010].

PMID- 22590253
TI  - [2-(2,5-Dichloro-benz-yl)-4-hy-droxy-1,1-dioxo-2H-1,2-benzothia-zin-3-yl](phen
      yl)methanone.
AB  - In the title mol-ecule, C(22)H(15)Cl(2)NO(4)S, the heterocyclic thia-zine ring
      adopts a half-chair conformation, with the S and N atoms displaced by 0.343 (5)
      and 0.402 (5) A, respectively, on opposite sides of the mean plane formed by the
      remaining ring atoms. The mol-ecular structure is consolidated by an intra
      molecular O-H?O hydrogen bond, which generates an S(?) ring. In the crystal, the
      molecules are linked by C-H?O interactions into [010] chains.

PMID- 22590254
TI  - 2-(4-Amino-phen-yl)-3,4,5,6-tetra-hydro-pyrimidin-1-ium chloride.
AB  - In the title compound, C(10)H(14)N(3) (+).Cl(-), the tetra-hydro-pyridinium ring
      of the cation, which adopts a slightly distorted envelope conformation, is
      disordered over two orientations with an occupancy ratio of 0.653 (5):0.347 (5).
      The amidinium fragment of the major conformer is twisted relative to the benzene
      ring by 22.5 (6) degrees  and the two C-N bond lengths of this fragment are
      similar [1.3228 (16) and 1.319 (2) A]. In the crystal, the chloride anions are
      involved in three N-H?Cl hydrogen bonds, which link the components into a two
      dimensional hydrogen-bonded network parallel to (010).

PMID- 22590255
TI  - (R)-2,2'-Bis(meth-oxy-meth-oxy)-1,1'-binaphth-yl.
AB  - The asymmetric unit of the title compound, C(24)H(22)O(4), contains two
      independent mol-ecules in both of which the naphthalene ring systems adopts a
      transoid arrangement. The dihedral angles between the naphthalene ring system in
      the two mol-ecules are 83.0 (1) and 89.0 (1) degrees . There are slight
      differences in the C(H(3))-O-C(H(2))-O- torsion angles of the eqivalent meth-oxy
      meth-oxy groups. In the crystal, weak C-H?O hydrogen bonds are present.

PMID- 22590256
TI  - 1-{[4'-(1H-1,2,4-Triazol-2-ium-1-ylmeth-yl)biphenyl-4-yl]meth-yl}-1H-1,2,4
      triazol-2-ium bis-(3-carb-oxy-5-iodo-benzoate)-5-iodo-benzene-3,5-dicarb-oxy-lic
      acid-water (1/2/2).
AB  - The neutral carb-oxy-lic acid mol-ecule and the carboxyl-ate anion in the title
      compound, C(18)H(18)N(6) (2+).2C(8)H(4)IO(4) (-).2C(8)H(5)IO(4).2H(2)O, are both
      nearly planar (r.m.s. deviations = 0.034 and 0.045 A, respectively). In the
      cation, the mid-point of the C-C bond linking the two benzene rings lies on a
      center of inversion, and the triazole ring is approximately perpendicular to the
      adjacent benzene ring [dihedral angle = 83.2 (3) degrees ]. In the crystal, the
      cations, anions, carb-oxy-lic acid and lattice water mol-ecules are linked by N
      H?O, O-H?N and O-H?O hydrogen bonds, generating a ribbon running along [1-10].
      The crystal studied was a non-merohedral twin with the components in a 51.2
      (1):48.8 (1) ratio.

PMID- 22590257
TI  - 2-[7-Chloro-1,1-dioxo-2-(2,4,5-trifluoro-benz-yl)-3,4-dihydro-2H-1,2,4-benzothia
      diazin-4-yl]acetic acid.
AB  - In the mol-ecule of the title compound, C(16)H(12)ClF(3)N(2)O(4)S, the thia
      diazine ring adopts a half-chair conformation. The dihedral angle between the
      benzene ring of the benzothia-diazine ring system and trifluoro-phenyl group is
      15.02 (7) degrees . In the crystal, centrosymmetrically related mol-ecules are
      linked into dimers via pairs of O-H?O hydrogen bonds, generating R(2) (2)(8) ring
      motifs. The dimers are further connected into a three-dimensional network by C
      H?O hydrogen bonds.

PMID- 22590258
TI  - 2-[1,1-Dioxo-2-(2,4,5-trifluoro-benz-yl)-2H-1,2-benzothia-zin-4-yl]acetic acid.
AB  - In the title compound, C(17)H(12)F(3)NO(4)S, the heterocyclic thia-zine ring
      adopts a half-chair conformation with the S and the N atoms displaced by -0.608
      (3) and 0.105 (3) A, respectively, from the mean plane formed by the remaining
      ring atoms. The dihedral angle between the two benzene rings is 36.63 (8) degrees
      and the acetic acid group is inclined at right angles [89.78 (8)  degrees ] to
      the mean plane formed by the C atoms of the thia-zine ring. The crystal structure
      features O-H?O and C-H?O hydrogen bonds.

PMID- 22590259
TI  - 5-Chloro-2-nitro-phenol.
AB  - The asymmetric unit of the title compound, C(6)H(4)ClNO(3), contains two
      independent mol-ecules in which the dihedral angles between the benzene ring and
      the nitro groups are 2.5 (1) and 8.5 (1) degrees . Intra-molecular O-H?O hydrogen
      bonds involving the hy-droxy and nitro substituents result in the formation of
      S(6) six-membered rings. In the crystal, O-H?O, O-H?Cl and C-H?O hydrogen bonds
      together with Cl?O contacts [3.238 (3) and 3.207 (3) A] generate a three
      dimensional network.

PMID- 22590260
TI  - A second ortho-rhom-bic polymorph of 4-(Pyridin-4-ylmethoxy)phenol [corrected].
AB  - The crystal structure of the title compound, C(12)H(11)NO(2), represents a new
      ortho-rhom-bic polymorph II of the previously reported ortho-rhom-bic form I
      [Zhang et al. (2009 ?) Acta Cryst. E65, o3160]. In polymorph II, the six-membered
      rings form a dihedral angle of 13.8 (1) degrees  [71.6 (1) degrees  in I], and O
      H?N hydrogen bonds link mol-ecules into chains along [100], whereas the crystal
      structure of I features hydrogen-bonded centrosymmetric dimers.

PMID- 22590261
TI  - (1RS,2SR,5SR)-9-Benzyl-2-[(1RS)-1-hy-droxy-benz-yl]-9-aza-bicyclo-[3.3.1]nonan-3
      one from synchrotron data.
AB  - In the crystal structure of the racemic title compound, C(22)H(25)NO(2), solved
      and refined against sychrotron diffraction data, the hy-droxy group and the
      carbonyl O atom participate in the formation of O-H?O hydrogen bonds between
      pairs of enanti-omers related by a crystallographic centre of symmetry.

PMID- 22590262
TI  - N'-[(5-Methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)(thio-phen-2-yl)methyl
      idene]benzohydrazide.
AB  - In the title compound, C(22)H(18)N(4)O(2)S, the seven-membered ring generated by
      an intra-molecular N-H?O hydrogen bond adopts an envelope conformation in both of
      the two independent mol-ecules in the asymmetric unit. In the crystal, mol-ecules
      are linked into C(9) chains along [100] by N-H?O hydrogen bonds. The mol-ecules
      are also weakly linked by C-H?O and C-H?N inter-actions, forming dimers with edge
      connected R(2) (2)(9) rings. The dimers are inter-linked by further weak C-H?N
      hydrogen bonds into chains along [010].

PMID- 22590263
TI  - 1-[3-(Anthracen-9-yl)-5-(pyridin-2-yl)-4,5-dihydro-1H-pyrazol-1-yl]ethanone.
AB  - In the title compound, C(24)H(19)N(3)O, the pyrazoline ring adopts an envelope
      conformation with the C atom linking to the pyridine ring as the flap. The mean
      plane of the pyrazoline ring makes dihedral angles of 85.54 (4) and 81.66 (3)
      degrees  with the pyridine ring and the anthracene ring system, respectively. In
      the crystal, mol-ecules are linked by C-H?O hydrogen bonds. In addition, weak pi
      pi inter-actions [centroid-centroid distances = 3.695 (3)-3.850 (7) A] are
      observed.

PMID- 22590264
TI  - 1,1,2,2-Tetra-kis(dimethyl-amino)-ethane-1,2-diium bis-(tetra-phenyl-borate)
      acetone disolvate.
AB  - The title compound, C(10)H(24)N(4) (2+).2C(24)H(20)B(-).2C(3)H(6)O, crystallizes
      with two acetone solvent mol-ecules per asymmetric unit. In the dication, both
      amidinium units are twisted about the central C-C single bond by 63.8 (3) degrees
      and the positive charges are delocalized over both N-C-N planes.

PMID- 22590265
TI  - 1-(3,5-Dimeth-oxy-benz-yl)-1H-pyrrole.
AB  - The title compound, C(13)H(15)NO(2), was synthesized from 3,5-dimeth-oxy
      benzaldehyde. The dihedral angle between the pyrrole and benzene rings is 89.91
      (5) degrees . In the crystal, weak C-H?O and C-H?pi interactions link the mol
      ecules into a three-dimensional network.

PMID- 22590266
TI  - (E)-Methyl 2-({2-eth-oxy-6-[(E)-(hy-droxy-imino)-meth-yl]phen-oxy}meth-yl)-3
      phenyl-acrylate.
AB  - In the title compound, C(20)H(21)NO(5), the dihedral angle between the mean
      planes through the two rings is 47.1 (8) degrees . The enoate group assumes an
      extended conformation. The hy-droxy-ethanimine group is essentially coplanar with
      the benzene ring, the largest deviation from the mean plane being 0.061 (1) A for
      the O atom. In the crystal, mol-ecules are linked into cyclic centrosymmetric
      dimers with an R(2) (2)(6) motif via pairs of O-H?N hydrogen bonds. Inter
      molecular C-H?O hydrogen bonds form a C(8) chain along the b axis. The crystal
      packing is further stabilized by C-H?pi inter-actions.

PMID- 22590267
TI  - 1-(4-Chloro-2-fluoro-5-nitro-phen-yl)-4-difluoro-methyl-3-methyl-1H-1,2,4-triazol
      5(4H)-one.
AB  - In the title compound, C(10)H(6)ClF(3)N(4)O(3), the dihedral angle between the
      benzene ring and the triazolone ring is 59.9 (1) degrees , while the nitro
      substituent subtends an angle of 39.5 (1) degrees  to the benzene ring plane. In
      the crystal, pairs of mol-ecules form inversion dimers via C-H?O hydrogen bonds.

PMID- 22590268
TI  - Bis[(diamino-methyl-idene)aza-nium] 5-(1-oxido-1H-1,2,3,4-tetra-zol-5-yl)-1H
      1,2,3,4-tetra-zol-1-olate.
AB  - The anion of the title salt, 2[C(NH(2))(3)](+).C(2)N(8)O(2) (2-), lies on a
      center of inversion and its two five-membered rings are coplanar. The guanidinium
      cation forms N-H?O and N-H?N hydrogen bonds to the anion, generating an eight
      membered ring. Other hydrogen bonds lead to the formation of a three-dimensional
      network.

PMID- 22590269
TI  - Methyl 2-({6-[(1-meth-oxy-2-methyl-1-oxopropan-2-yl)carbamo-yl]pyridin-2
      yl}formamido)-2-methyl-propano-ate.
AB  - In the title compound, C(17)H(23)N(3)O(6), the two meth-oxy-carbonyl C-O-C=O
      planes are inclined at dihedral angles of 5.3 (4) and 83.9 (4) degrees  with
      respect to the central pyridine ring. An intra-molecular N-H?O hydrogen bond
      generates an S(5) ring motif. In the crystal, mol-ecules are linked into a chain
      along the c axis via C-H?O hydrogen bonds.

PMID- 22590270
TI  - 2-[(2-Meth-oxy-eth-yl)sulfan-yl]-4-(2-methyl-prop-yl)-6-oxo-1,6-dihydro
      pyrimidine-5-carbonitrile.
AB  - In the title compound, C(12)H(17)N(3)O(2)S, the 4-methyl-2-methyl-sulfanyl-6-oxo
      1,6-dihydro-pyrimidine-5-carbonitrile part of the mol-ecule is almost planar
      (r.m.s deviation = 0.062 A). In the crystal, mol-ecules form centrosymmetric
      dimers via pairs of N-H?O hydrogen bonds.

PMID- 22590271
TI  - 5-Benzoyl-13-bromo-4-hy-droxy[2.2]paracyclo-phane.
AB  - The title compound, C(23)H(19)BrO(2), was synthesized from 13-bromo-4-hy
      droxy[2.2]paracyclo-phane and benzoyl chloride. The hy-droxy and carbonyl groups
      are involved in intra-molecular O-H?O hydrogen bonding. The crystal packing
      exhibits weak C-H?O inter-actions, which link the mol-ecules into sheets parallel
      to the bc plane.

PMID- 22590272
TI  - 1-Methyl-2,3-dihydro-1H-benzimidazole-2-selone.
AB  - The title compound C(8)H(8)N(2)Se, is the product of the reaction of 2-chloro-1
      methyl-benzimidazole with sodium hydro-selenide. The mol-ecule is almost planar
      (r.m.s. deviation = 0.041 A) owing to the presence of the long chain of
      conjugated bonds (Se=C-NMe-C=C-C=C-C=C-NH). The C=Se bond length [1.838 (2) A]
      corresponds well to those found in the close analogs and indicates its pronounced
      double-bond character. In the crystal, mol-ecules form helicoidal chains along
      the b axis by means of N-H?Se hydrogen bonds.

PMID- 22590273
TI  - 4-[(2'-Cyano-biphenyl-4-yl)meth-yl]morpholin-4-ium hexa-fluoridophosphate.
AB  - In the cation of the title compound, C(18)H(19)N(2)O(+).PF(6) (-), the morpholine
      ring adopts the usual chair conformation and the dihedral angle between the
      benzene rings is 67.55 (11) degrees . The F atoms of the anion are disordered
      over two orientations with a refined occupancy ratio of 0.65 (2):0.35 (2). In the
      crystal, inter-molecular N-H?N hydrogen bonds link the cations into chains
      parallel to the c axis. The crystal packing is further enforced by inter-ionic C
      H?F hydrogen bonds.

PMID- 22590274
TI  - 2-(5-Bromo-thio-phen-2-yl)-5-[5-(10-ethyl-phenothia-zin-3-yl)thio-phen-2-yl]
      1,3,4-oxadiazole.
AB  - The mol-ecule of the title compound, C(24)H(16)BrN(3)OS(3), contains three
      approximately planar fragments, viz. an oxadiazole ring plus two adjacent thio
      phene groups, and two phenothia-zine benzene rings, with largest deviations from
      the least-squares planes of 0.051 (3), 0.019 (4) and 0.014 (3) A, respectively.
      The phenothia-zine unit adopts a butterfly conformation, with a dihedral angle of
      38.06 (15) degrees  between the terminal benzene rings. The dihedral angle
      between the 2,5-bis-(thio-phen-2-yl)oxadiazole unit and the attached benzene ring
      is 15.35 (11) degrees . In the crystal, mol-ecules form stacks along the b-axis
      direction; neighboring mol-ecules within the stack are related by inversion
      centers, with shortest inter-centroid separations of 3.741 (2) and 3.767 (2) A.

PMID- 22590275
TI  - N-(2,6-Dichloro-phen-yl)-2-(naphthalen-1-yl)acetamide.
AB  - In the title compound, C(18)H(13)Cl(2)NO, the naphthalene ring system and the
      benzene ring form dihedral angles of 74.73 (13) and 62.53 (16) degrees ,
      respectively, with the acetamide grouping [maximum deviation = 0.005 (3) A]. The
      naphthalene ring system forms a dihedral angle of 75.14 (13) degrees  with the
      benzene ring. In the crystal, mol-ecules are linked by N-H?O hydrogen bonds,
      forming C(4) chains propagating in [010]. The O atom also accepts two C-H?O inter
      actions.

PMID- 22590276
TI  - Dimethyl 2-[23-oxo-22,24-diphenyl-8,11,14-trioxa-25-aza-tetra-cyclo
      [19.3.1.0(2,7).0(15,20)]penta-cosa-2,4,6,15(20),16,18-hexaen-25-yl]but-2
      enedioate.
AB  - The title compound, C(39)H(37)NO(8), is a product of the Michael addition of the
      cyclic secondary amine subunit of aza-14-crown-4 ether to dimethyl acetyl
      enedicarboxyl-ate. The piperidinone ring exhibits a distorted chair conformation
      and the dimethyl acetyl-enedicarboxyl-ate fragment has a cis configuration with a
      dihedral angle of 56.61 (5) degrees  between the two carboxyl-ate groups. The
      crystal packing is stabilized by the weak C-H?O hydrogen bonds.

PMID- 22590277
TI  - Propyl 2-(4-methyl-benzene-sulfonamido)-benzoate.
AB  - In the title compound, C(17)H(19)NO(4)S, the terminal ethyl group is disordered
      over two sets of sites, with refined site occupancies of 0.536 (7) and 0.464 (7).
      The dihedral angle between the two aromatic rings is 81.92 (12) degrees . The mol
      ecular conformation is stabilized by intra-molecular N-H?O and C-H?O hydrogen
      bonds, which generate S(6) motifs. In the crystal, mol-ecules are linked by C-H?O
      hydrogen bonds, forming chains along the b axis.

PMID- 22590278
TI  - (R)-N-(Biphenyl-4-yl)-tert-butane-sulfinamide.
AB  - In the title compound, C(16)H(19)NOS, the dihedral angle between the two aromatic
      rings is 38.98 (8) degrees . The crystal structure is stabilized by N-H?O
      hydrogen bonds, which link neighbouring mol-ecules into chains running parallel
      to the a axis.

PMID- 22590279
TI  - 5,6,7,5'-Tetra-meth-oxy-3',4'-methyl-ene-dioxy-flavone monohydrate.
AB  - THE TITLE COMPOUND [SYSTEMATIC NAME: 5,6,7-trimeth-oxy-2-(7-meth-oxy-1,3-dihydro
      2-benzofuran-5-yl)-4H-chromen-4-one monohydrate], C(20)H(18)O(8).H(2)O, was
      isolated from the popular Chinese medicinal plant Entada phaseoloides. In the
      crystal, inversion-related mol-ecules are joined by pairs of weak C-H?O hydrogen
      bonds. The dimers are further inter-connected by a bridging water mol-ecule via
      weak C-H?O(water) and pairs of (O-H)(water)?O hydrogen bonds into a linear tape
      running parallel to the b axis.

PMID- 22590280
TI  - 4,5-Dibromo-1,2-dimethyl-1H-imidazol-3-ium bromide.
AB  - In the title salt, C(5)H(7)Br(2)N(2) (+).Br(-), the cation and anion are
      connected by an N-H?Br hydrogen bond. In the crystal, there are inter-calated
      layers parallel to (10-2) in which bromide ions are located between the cations.
      Weak inter-molecular C-H?Br hydrogen bonds are also observed.

PMID- 22590281
TI  - 2,4-Dimethyl-6-nitro-aniline.
AB  - The asymmetric unit of the title compound, C(8)H(10)N(2)O(2), contains two
      independent mol-ecules, which are linked by weak N-H?O hydrogen-bonding inter
      actions between the amino and nitro groups. The independent molecules are both
      approximately planar with r.s.d. deviations of 0.0216 and 0.0161 A.

PMID- 22590282
TI  - (Z)-2-(4-Chloro-benzyl-idene)benzo[d]thia-zolo[3,2-a]imidazol-3(2H)-one.
AB  - The mol-ecule of the title compound, C(16)H(9)ClN(2)OS, is approximately planar,
      the dihedral angle between the thia-zolo[3,2-a]benzimidazole ring system and the
      4-chloro-phenyl ring being 2.10 (5) degrees . An intra-molecular C-H?S inter
      action generates an S(6) ring motif. In the crystal, mol-ecules are stacked into
      columns along the b axis by pi-pi inter-actions with centroid-centroid distances
      of 3.6495 (7)-3.9546 (8) A.

PMID- 22590283
TI  - rac-Methyl 2-(2-formyl-4-nitro-phen-oxy)hexa-noate.
AB  - In the racemic title compound, C(14)H(17)NO(6), the plane of the ester group of
      the methyl hexa-noate side chain makes a dihedral angle of 80.0 (2) degrees  with
      the benzene ring, while the nitro group is approximately coplanar with the
      benzene ring [dihedral angle = 10.3 (2) degrees ]. In the crystal, mol-ecules
      form weak aromatic C-H?O(nitro) hydrogen-bonding inter-actions, giving inversion
      dimers [graph set R(2) (2)(8)].

PMID- 22590284
TI  - 1-Eth-oxy-methyl-5-methyl-9-phenyl-6,7,8,9-tetra-hydro-1H-pyrimido[4,5
      b][1,4]diazepine-2,4(3H,5H)-dione.
AB  - The title compound, C(17)H(22)N(4)O(3), comprises a 1,4-diazepine ring in a twist
      boat conformation fused to a pyrimidine ring. The dihedral angle between the
      pyrimidine and phenyl rings is 80.8 (1) degrees . The crystal packing features N
      H?O and C-H?O hydrogen bonds.

PMID- 22590285
TI  - 4-Amino-8-cyclo-pent-yloxy-7-meth-oxy-2H-chromen-2-one monohydrate.
AB  - The asymmetric unit of the title compound, C(15)H(17)NO(4).H(2)O, contains two
      organic mol-ecules with marginal differences between them and two water
      molecules. The chromine rings in both mol-ecules are essentially planar, with
      maximum deviations of 0.012 (2) and 0.060 (2) A. The five-membered cyclo-pentane
      rings adopt envelope conformations in both mol-ecules. In the crystal, the
      components are linked by N-H?O, O-H?O and C-H?O hydrogen bonds, resulting in a
      three-dimensional network.

PMID- 22590286
TI  - 2-Eth-oxy-6-[1-(3-eth-oxy-2-hy-droxy-benz-yl)-2,3-dihydro-1H-benzimidazol-2
      yl]phenol acetonitrile monosolvate.
AB  - The title compound, C(24)H(24)N(2)O(4).CH(3)CN, a disubstituted benzimidazole,
      crystallized as an acetonitrile monosolvate. The benzene ring of the 2-eth-oxy-6
      methyl-phenol substiuent is approximately perpendicular to the nearly planar
      benzimidazole ring system [maximum deviation = 0.016 (1) A], making a dihedral
      angle of 84.27 (8) degrees . The benzene ring of the 2-eth-oxy-phenol substituent
      is inclined to the benzimidazole mean plane by 29.68 (8) degrees . The dihedral
      angle between the benzene rings is 80.36 (9) degrees . In the mol-ecule, there
      are strong O-H?N and O-H?O hydrogen bonds. In the crystal, mol-ecules are
      connected by bifurcated O-H?(O,O) hydrogen bonds, forming chains propagating
      along [010].

PMID- 22590287
TI  - 4,4'-Dinitro-2,2'-[propane-1,3-diylbis(iminiumylmethanylyl-idene)]diphenolate.
AB  - The title compound, C(17)H(16)N(4)O(6), is a Schiff base, which is found as a bis
      zwitterion in the solid state. The geometry around the iminium N atom indicates
      sp(2)-hybridization. The diiminiumpropyl-ene chain is in an approximate double
      gauche conformation, with average N-C-C-C torsion angles of 69.3 degrees . The
      zwitterion shows strong intra-molecular N-H?O hydrogen bonds between the iminium
      N and phenolate O atom. In the crystal, bifurcated N-H?(O,O) hydrogen bonds
      assemble pairs of molecules into inversion dimers.

PMID- 22590288
TI  - Ethyl 2-[4,5-bis-(butyl-sulfan-yl)-1,3-dithiol-2-yl-idene]-1,3-dithiolo[4,5
      c]pyrrole-4-carboxyl-ate.
AB  - In the title mol-ecule, C(19)H(25)NO(2)S(6), the butyl chains are each disordered
      over two conformations in a 0.689 (10):0.311 (10) ratio. In the crystal, pairs of
      N-H?O hydrogen bonds link mol-ecules into centrosymmetric dimers. Short S?S
      contacts of 3.553 (4) A are observed.

PMID- 22590289
TI  - Ethyl (E)-3-[1'-ethyl-2-oxo-4'-(phenyl-sulfon-yl)-2H-spiro-[acenaphthyl-ene-1,2'
      pyrrolidine]-3'-yl]acrylate.
AB  - In the title compound, C(28)H(27)NO(5)S, the five-membered pyrrolidine ring,
      which exhibits an envelope conformation (the C atom at the spiral junction being
      the flap atom), makes dihedral angles of 57.37 (10) and 86.84 (8) degrees ,
      respectively, with the phenyl ring and the acenaphthyl-ene ring system. In the
      crystal, mol-ecules associate via two C-H?O hydrogen bonds, forming R(2) (2)(20)
      and R(2) (2)(10) graph-set motifs.

PMID- 22590290
TI  - Benzyl 3-(2-methyl-phen-yl)dithio-carbazate.
AB  - In the title compound, C(15)H(16)N(2)S(2), the central C(2)N(2)S(2) unit is
      essentially planar (r.m.s. deviation = 0.047 A) and forms dihedral angles of
      68.26 (4) and 65.99 (4) degrees  with the phenyl and benzene rings, respectively,
      indicating a twisted mol-ecule. Supra-molecular chains with a step topology and
      propagating along [100] feature in the crystal packing, mediated through N-H?S
      hydrogen bonds. The chains are consolidated into a three-dimensional architecture
      by C-H?pi inter-actions.

PMID- 22590291
TI  - N-(2-Chloro-benzo-yl)-4-methyl-benzene-sulfonamide.
AB  - In the title compound, C(14)H(12)ClNO(3)S, the C=O bond is syn to the Cl
      substituent in the adjacent benzene ring. The C-S-N-C torsion angle is -80.6 (6)
      degrees . The chloro-benzoyl ring is disordered and was refined using a split
      model [occupancy ratio 0.537 (3):0.463 (3)]. In the crystal, mol-ecules are
      linked by pairs of N-H?O(S) hydrogen bonds, forming inversion dimers.

PMID- 22590292
TI  - Dimethyl 5,5'-methyl-enebis(2-hy-droxy-benzoate).
AB  - In the title compound, C(17)H(16)O(6), the two methyl salicylate moieties are
      related by crystallographic twofold rotational symmetry with the two benzene
      rings close to being perpendicular [inter-ring dihedral angle = 86.6 (8) degrees
      ]. Intra-molecular phenolic O-H?O hydrogen bonds with carboxyl O-atom acceptors
      are present, with these groups also involved in centrosymmetric cyclic inter
      molecular O-H?O hydrogen-bonding associations [graph set R(2) (2)(4)], giving
      infinite chains extending across (101).

PMID- 22590293
TI  - 5-Bromo-N-(3,4-dimeth-oxy-benz-yl)pyridin-2-amine.
AB  - The title compound, C(14)H(15)BrN(2)O(2), an inter-mediate in drug discovery, was
      synthesized by the reaction of 5-bromo-pyridin-2-amine and 3,4-dimeth-oxy
      benzaldehyde. In the crystal, molecules are linked via pairs ofN-H?N hydrogen
      bonds, leading to the formation of inversion dimers. A short contact occurs
      between the aryl H atom (ortho position from N) and the centroid of the benzene
      ring.

PMID- 22590294
TI  - 2-Amino-3-[(E)-(2-hy-droxy-3-methyl-benzyl-idene)amino]-but-2-ene-dinitrile.
AB  - The title compound, C(12)H(10)N(4)O, is a Schiff base obtained from the
      condensation of diamino-maleonitrile and 2-hy-droxy-3-methyl-benzaldehyde. The
      mol-ecule is roughly planar, with an r.m.s. deviation of 0.0354 A, and adopts the
      phenol-imine tautomeric form. An intra-molecular O-H?N hydrogen bond involving
      the O-H group and the azomethine N atom generates an S(6) ring. In the crystal,
      there are two N-H?N hydrogen bonds.

PMID- 22590295
TI  - 3-Ethyl-4-[(E)-(4-fluoro-benzyl-idene)amino]-1H-1,2,4-triazole-5(4H)-thione.
AB  - In the title compound, C(11)H(11)FN(4)S, the dihedral angle between the 1,2,4
      triazole ring and the benzene ring is 25.04 (12) degrees  and an intra-moleuclar
      C-H?S inter-action leads to an S(6) ring. In the crystal, inversion dimers linked
      by pairs of N-H?S hydrogen bonds generate R(2) (2)(8) loops.

PMID- 22590296
TI  - 2-Chloro-N-(2,6-dimethyl-phen-yl)benzamide.
AB  - In the title compound, C(15)H(14)ClNO, the dihedral angle between the benzoyl and
      the aniline rings is 3.30 (18) degrees . In the crystal, N-H?O hydrogen bonds
      link the mol-ecules into chains running along the a axis.

PMID- 22590297
TI  - (1H-1,2,3-Benzotriazol-1-yl)methyl benzoate.
AB  - In the title compound, C(14)H(11)N(3)O(2), the dihedral angle between the phenyl
      ring and the benzotriazole ring system is 76.80 (19) degrees  and the mol-ecule
      has an L-shaped conformation. In the crystal, weak aromatic pi-pi stacking is
      observed, the closest centroid-centroid distance being 3.754 (2) A.

PMID- 22590298
TI  - 2,5-Dimethyl-3-(4-methyl-phenyl-sulfin-yl)-1-benzofuran.
AB  - In the title compound, C(17)H(16)O(2)S, the 4-methyl-phenyl ring makes a dihedral
      angle of 88.28 (5) degrees  with the mean plane [mean deviation = 0.009 (1) A] of
      the benzofuran fragment. In the crystal, mol-ecules are linked by weak C-H?O and
      C-H?pi inter-actions.

PMID- 22590299
TI  - Redetermination of 1,3-diammonio-1,2,3-tride-oxy-cis-inositol dichloride.
AB  - The crystal structure of the title compound, C(6)H(16)N(2)O(3) (2+).2Cl(-), has
      been reported previously by Palm [Acta Cryst. (1967 ?), 22, 209-216] from
      Weisenberg camera data, with R1 = 10.5%, isotropic refinement of non-H atoms and
      H atoms not located. We remeasured a data set of the title compound and present a
      more precise structure determination. The asymmetric unit contains two unique 1,3
      diammonio-1,2,3-tride-oxy-cis-inositol cations and four Cl(-) counter-ions. The
      cyclo-hexane rings of both inositol cations adopt chair conformations with two
      axial hy-droxy groups. An extended network of hydrogen bonds is formed. The four
      chloride counter ions are hydrogen bonded to the hydroxy and ammonium groups of
      the cations by N-H?Cl and O-H?Cl interactions. The cations are aligned into wavy
      layers by cation?cation interactions of the form N-H?O(ax), N-H?O(eq) and O(ax)
      H?O(eq). Intramolecular hydrogen bonding between the axial hydroxy groups is,
      however, not observed.

PMID- 22590300
TI  - 4-[(1E)-3-(2,6-Dichloro-3-fluoro-phen-yl)-3-oxoprop-1-en-1-yl]benzonitrile.
AB  - In the title mol-ecule, C(16)H(8)Cl(2)FNO, the benzene rings form a dihedral
      angle of 78.69 (8) degrees . The F atom is disordered over two positions in a
      0.530 (3):0.470 (3) ratio. The crystal packing exhibits pi-pi inter-actions
      between dichloro-substituted rings [centroid-centroid distance = 3.6671 (10) A]
      and weak inter-molecular C-H?F contacts.

PMID- 22590301
TI  - 2-Amino-4-(4-chloro-phen-yl)-5-oxo-5,6,7,8-tetra-hydro-4H-chromene-3
      carbonitrile.
AB  - In the title moleclue, C(16)H(13)ClN(2)O(2), the cyclo-hexene ring is in a sofa
      conformation. The pyran ring is essentialy planar [maximum deviation = 0.038 (2)
      A] and forms a dihedral angle of 89.68 (10) degrees  with the benzene ring. In
      the crystal, mol-ecules are linked by pairs of N-H?N hydrogen bonds, forming
      inversion dimers with R(2) (2)(12) ring motifs. These dimers are further linked
      by N-H?O hydrogen bonds into chains along [110]. Weak C-H?O hydrogen bonds are
      also present.

PMID- 22590302
TI  - (R)-(3-Carb-oxy-2-hy-droxy-prop-yl)tri-methyl-aza-nium chloride.
AB  - In the title salt (common name l-carnitine hydro-chloride), C(7)H(16)NO(3)
      (+).Cl(-), the organic cation features a carb-oxy-lic part (-CO(2)H) having
      unambigous single- and double-bonds [1.336 (2), 1.211 (2) A]. There is a large N
      C-C bond angle [115.9 (1) degrees ] for the C atom connected to the bulky
      trimethyl-amino substituent. In the crystal, the acid H atom forms a hydrogen
      bond to the chloride anion, whereas the hydroxyl H atom forms a longer hydrogen
      bond to the anion, generating a helical chain running along [001].

PMID- 22590303
TI  - 2,6-Dichloro-N-(4-methyl-phen-yl)benzamide.
AB  - In the title compound, C(14)H(11)Cl(2)NO, the two benzene rings are non-coplanar
      [dihedral angle = 60.9 (3) degrees ]. In the crystal, an amide N-H?O hydrogen
      bond links the mol-ecules into chains which extend along (001).

PMID- 22590304
TI  - 5,11,17,23,29,35-Hexa-tert-butyl-37,38,39,40,41,42-hexa-kis-(eth-oxy-carbonyl
      meth-oxy)calix[6]arene acetonitrile disolvate.
AB  - In the title compound, C(90)H(120)O(18).2CH(3)CN, the calix[6]arene has a 1,2,3
      alternate conformation and possesses inversion symmetry. It crystallizes as an
      acetonitrile disolvate, with a half-mol-ecule of calix[6]arene and one mol-ecule
      of solvent in the asymmetric unit. In the crystal, the two solvent mol-ecules are
      enclosed in voids between the calix[6]arene mol-ecules. They form weak C-H?O
      hydrogen bonds involving an O atom of the lower rim substituent. The cavity of
      the calix[6]arene itself is enclosed by two opposite phenol rings, which are
      turned into the cavity due to the presence of a C-H?pi inter-action. The
      calix[6]arene mol-ecule exhibits disorder of one substituent on its lower rim
      [occupancy ratio 0.897 (3):0.103 (3)].

PMID- 22590305
TI  - 3-Eth-oxy-carbonyl-2-hy-droxy-6-meth-oxy-4-methyl-benzoic acid.
AB  - The title compound, C(12)H(14)O(6), a substituted isophthalic acid monoester
      which was isolated from the lichen Thamnolia vermicularis var. subuliformis,
      displays intra-molecular carbox-yl-meth-oxy O-H?O and hy-droxy-carboxyl O-H?O
      hydrogen-bonding inter-actions. The terminal methyl group of the ethyl ester is
      disordered over two sets of sites with occupancies of 0.599 (19) and 0.401 (19).

PMID- 22590306
TI  - N'-[(E)-4-Benz-yloxy-2-hy-droxy-benzyl-idene]-4-nitro-benzohydrazide monohydrate.
AB  - The title compound, C(21)H(17)N(3)O(5).H(2)O, exists in the keto form with an E
      conformation with respect to the azomethine double bond. The twist angles between
      the aromatic rings are in the range 4.67 (10)-17.54 (10) degrees . A water mol
      ecule of solvation is present in the lattice. A conventional intra-molecular O
      H?N hydrogen bond increases the rigidity of the mol-ecule. Inter-molecular O-H?O,
      N-H?O and C-H?O hydrogen-bonding inter-actions establish a supra-molecular
      linkage among the mol-ecules in the crystal structure. There are also C-H?pi
      inter-actions present.

PMID- 22590308
TI  - 1,3-Diammonio-1,2,3-tride-oxy-cis-inositol sulfate.
AB  - In the crystal structure of the title compound, C(6)H(16)N(2)O(3) (2+).SO(4) (2
      ), each cation forms three O-H?O and five N-H?O hydrogen bonds to six
      neighbouring sulfate anions. In addition, interlinking of the cations by N-H?O
      interactions is also observed. The cyclo-hexane ring adopts a chair conformation
      with two axial hy-droxy groups. Although the separation of 2.928 A is almost
      ideal for a hydrogen bond, intra-molecular hydrogen bonding between these two hy
      droxy groups is not observed.

PMID- 22590307
TI  - 9,10-Dioxoanthracene-1,4-diyl bis-(4-methyl-benzene-sulfonate).
AB  - The title mol-ecule, C(28)H(20)O(8)S(2), has a T-shaped conformation. The central
      9,10-anthraquinone moiety is bow-shaped with the two outer aromatic rings being
      inclined to one another by 13.99 (11) degrees . The benzenesulfonate rings are
      inclined to one another by 47.35 (12) degrees , and by 34.51 (11) and 17.88 (11)
      degrees  to the bridging aromatic ring of the 9,10-anthraquinone moiety. In the
      crystal, C-H?O interactions link the mol-ecules into ribbons in [100].

PMID- 22590309
TI  - (E)-2,4,6-Trimethyl-N-(pyridin-2-yl-methyl-idene)aniline.
AB  - In the title compound, C(15)H(16)N(2), has an E conformation about the central
      N=C bond. The benzene and pyridine rings are almost normal to one another with a
      dihedral angle of 87.47(8) degrees . In the crystal, there are no classical
      hydrogen bonds.

PMID- 22590310
TI  - Benzo[1,2-b:4,5-b']dithio-phene-4,8-dione.
AB  - The title mol-ecule, C(10)H(4)O(2)S(2), is situated on a crystallographic center
      of inversion. In the crystal, weak hydrogen bonding contributes to the packing of
      the mol-ecules.

PMID- 22590311
TI  - 1,3-Bis[(naphthalen-2-ylsulfan-yl)meth-yl]benzene.
AB  - Mol-ecules of the title compound, C(28)H(22)S(2), are located on a
      crystallographic mirror plane with one half-mol-ecule in the asymmetric unit. The
      dihedral angle between the phenyl ring and the naphthyl unit is 83.14 (7) degrees
      . In the crystal, mol-ecules are inter-connected by C-H?S and C-H?pi inter
      actions.

PMID- 22590312
TI  - Dimethyl 3-(cyclo-propyl-carbon-yl)pyrrolo-[2,1-a]isoquinoline-1,2-dicarboxyl
      ate.
AB  - In the mol-ecular structure of the title compound, C(20)H(17)NO(5), two intra
      molecular C-H?O hydrogen bond generate six- and seven-membered ring motifs. The
      dihedral angles between the almost planar 13-atom triple-fused-ring system
      (r.m.s. deviation = 0.003 A) and the planes of the two meth-oxy-carbonyl
      substituents are 61.7 (2) and 33.01 (10) degrees .

PMID- 22590313
TI  - Cyclo-hexa-2,5-diene-1,4-dione-1,2,4,5-tetra-fluoro-3,6-diiodo-benzene (1/1).
AB  - The asymmetric unit of the title co-crystal adduct, C(6)H(4)O(2).C(6)F(4)I(2),
      comprises a half-mol-ecule each of cyclo-hexa-2,5-diene-1,4-dione and 1,2,4,5
      tetra-fluoro-3,6-diiodo-benzene. The C(6)F(4)I(2) mol-ecule is almost planar
      (r.m.s. deviation = 0.0062 A). In the crystal, the components are connected
      through O?I halogen bonds [3.017 (11) A], leading to the formation of wavelike
      chains along the a axis. The crystal packing also features C-H?F inter-actions.

PMID- 22590314
TI  - Dicyclo-hexyl-ammonium hydrogen phenyl-phospho-nate.
AB  - In the title salt, [(C(6)H(11))(2)NH(2)](+).[C(6)H(5)PO(2)(OH)](-), the anion is
      monodeprotonated and acts as both a hydrogen-bond donor and acceptor. The anions
      are linked by pairs of O-H?O inter-actions, forming inversion dimers with R(2)
      (2)(8) ring motifs. These dimers are bridged by two dicyclo-hexyl-aminium cations
      via pairs of N-H?O hydrogen bonds, giving R(4) (4)(12) ring motifs, forming
      chains propagating along [010]. The chains are bridged by C-H?O inter-actions,
      forming a two-dimensional network lying parallel to (101).

PMID- 22590315
TI  - (E,E)-N'-{4-[(2-Benzoyl-hydrazin-1-yl-idene)meth-yl]benzyl-idene}benzo-hydrazide.
AB  - In the title compound, C(22)H(18)N(4)O(2), the mol-ecules lie across an inversion
      centre. The dihedral angle between the mean planes of the central and terminal
      benzene rings is 66.03 (2) degrees . The mol-ecule displays trans and anti
      conformations about the C=N and N-N bonds, respectively. In the crystal, N-H?O
      hydrogen bonds, with the O atoms of C=O groups acting as acceptors, link the mol
      ecules into a chain along [101].

PMID- 22590316
TI  - 1,1'-(Butane-1,4-di-yl)bis-[2-(pyridin-2-yl)-1H-benzimidazole].
AB  - The complete mol-ecule of the title compound, C(28)H(24)N(6), is generated by
      inversion symmetry with the inversion centre located at the mid-point of the
      central C-C bond of the butanediyl unit. The benzimidazole and pyridine rings are
      almost coplanar, the dihedral angle between their mean planes being 6.86 (11)
      degrees .

PMID- 22590317
TI  - 7-Diethyl-amino-2-propyl-sulfan-yl-3-(1H-1,2,4-triazol-1-yl)-4H-thio-chromen-4
      one.
AB  - In the title compound, C(18)H(22)N(4)OS(2), the six-membered rings are almost
      coplanar, showing a dihedral angle between the mean planes of 9.0 (4) degrees ,
      while the triazol ring is nearly perpendicular to the thio-chromen-4-one unit,
      making an angle of 89.8 (4) degrees . In the crystal, C-H?N hydrogen bonds link
      the mol-ecules in a stacked arrangement along the c axis.

PMID- 22590318
TI  - 3-[(1-Hy-droxy-1-phenyl-propan-2-yl)amino]-5,5-dimethyl-cyclo-hex-2-enone.
AB  - The asymmetric unit of the title compound, C(17)H(23)NO(2), consists of two
      crystallographically independent mol-ecules (A and B). The cyclo-hexene rings in
      both mol-ecules adopt an envelope conformation. In the crystal, independent mol
      ecules, A and B, are each linked by inter-molecular bifurcated (N,O)-H?O hydrogen
      bonds, generating R(2) (1)(7) ring motifs and forming infinite chains along the b
      axis.

PMID- 22590319
TI  - 4-Benzyl-8-phenyl-1-thia-4-aza-spiro-[4.5]decan-3-one.
AB  - In the title compound, C(21)H(23)NOS, the thia-zolidine ring adopts a twist
      conformation about one of its C-S bonds, while the cyclo-hexane ring has a chair
      conformation. The S and N atoms attached to the spiro C atom are in axial and
      equatorial orientations, respectively. The thia-zolidine ring forms dihedral
      angles of 86.24 (14) and 31.82 (15) degrees  with the directly attached and
      remote terminal benzene rings, respectively. The dihedral angle between the two
      terminal benzene rings is 86.74 (14) degrees . In the crystal, the only
      significant directional inter-action is a weak C-H?pi bond, which generates [010]
      chains.

PMID- 22590320
TI  - 3-(1-Adamant-yl)-4-amino-1-(2-benzoyl-1-phenyl-eth-yl)-1H-1,2,4-triazol-5(4H)
      thione.
AB  - In the title compound, C(27)H(30)N(4)OS, the 3-(adamantan-1-yl)-4-amino-1H-1,2,4
      triazole-5(4H)-thione unit and the O atom are each disordered over two sets of
      sites with refined site-occupancies of 0.7630 (13) and 0.2370 (13). The 1,2,4
      triazole ring of the major component forms dihedral angles of 62.61 (17) and
      61.93 (16) degrees  with the benzene rings, while that of the minor component
      makes corresponding angles of 86.3 (4) and 79.1 (4) degrees . The dihedral angle
      between the benzene rings is 39.21 (16) degrees . The mol-ecular structure is
      stabilized by an intra-molecular C-H?N hydrogen bond, which generates an S(6)
      ring motif. In the crystal, mol-ecules are linked into inversion dimers by pairs
      of N-H?S hydrogen bonds.

PMID- 22590321
TI  - 3-Carbamoyl-1-(2-nitrobenzyl)pyridin-ium bromide.
AB  - In the title compound, C(13)H(12)N(3)O(3) (+).Br(-), the benzene and pyridinium
      rings form a dihedral angle of 82.0 (1) degrees . In the crystal, N-H?Br and N
      H?O hydrogen bonds link the components into chains along [001]. In addition, weak
      C-H?O and C-H?Br hydrogen bonds are observed.

PMID- 22590322
TI  - 2,3-Bis(thio-phen-2-yl)pyrazine-[2,3-f][1,10]phenanthroline.
AB  - The mol-ecule of the title compound, C(22)H(12)N(4)S(2), shows no
      crystallographic symmetry. The thiophene rings form different dihedral angles
      [40.15 (9) and 15.43 (10) degrees ] with the pyrazine ring. A strong pi-pi
      stacking inter-action occurs between adjacent pyrazine-[2,3
      f][1,10]phenanthroline units with an inter-planar distance of 3.4352 (16) A.

PMID- 22590323
TI  - 3-Amino-pyridin-1-ium 3-carb-oxy-benzo-ate.
AB  - In the title organic salt, C(5)H(7)N(2) (+).C(8)H(5)O(4) (-), the carb-oxy-lic
      group is nearly coplanar with the benzene ring [dihedral angle 1.9 (4) degrees ]
      whereas the carboxyl-ate group is twisted relative to the benzene ring by 13.6
      (4) degrees . In the crystal, N-H?O and O-H?O hydrogen bonds connect the
      components into a three-dimensional framework consisting of stacks of alternating
      pairs of anions and cations exhibiting pi-pi stacking inter-actions with centroid
      centroid distances in the range 3.676 (2)-3.711 (1) A. The pi-pi stacks extend
      along [110] and [-110].

PMID- 22590324
TI  - Dimethyl-ammonium 4-hy-droxy-benzoate.
AB  - In the crystal structure of the title compound, C(2)H(8)N(+).C(7)H(5)O(3) (-),
      the anions and cations are linked by O-H?O and N-H?O hydrogen bonds into layers
      parallel to the ac plane.

PMID- 22590325
TI  - (E)-1-(5-Bromo-2-hy-droxy-phen-yl)-3-[4-(dimethyl-amino)-phen-yl]prop-2-en-1-one.
AB  - In the title compound, C(17)H(16)BrNO(2), the two benzene rings make a dihedral
      angle of 7.4 (3) degrees ; the hy-droxy group links to the carbonyl group via an
      intra-molecular O-H?O hydrogen bond. In the crystal, weak C-H?O inter-actions
      link the mol-ecules into a supra-molecular chain running along the c axis.

PMID- 22590326
TI  - 2-[(2-Meth-oxy-benzyl-idene)amino]-phenol.
AB  - In the title compound, C(14)H(13)NO(2), the azomethine double bond adopts an E
      conformation and the benzene rings form a dihedral angle of 77.70 (7) degrees .
      In the crystal, mol-ecules are linked by O-H?N and C-H?O hydrogen bonds and
      arranged in a zigzag fashion, forming infinite chains parallel to the c axis,
      resulting in a graph-set R(2) (2)(9) motif.

PMID- 22590327
TI  - 5H-Imidazo[4,5-f][1,10]phenanthroline.
AB  - The title mol-ecule, C(13)H(8)N(4), is is essentially planar [r.m.s. deviation
      for all non-H atoms = 0.025 (3) A]. In the crystal, mol-ecules are connected
      through one weak bifurcated N-H?(N,N) hydrogen bond and three pi-pi stacking
      inter-actions between pyridine and imidazole rings [centroid-centroid distance =
      3.631 (8) A] and between pyridine and benzene rings [centroid-centroid distances
      = 3.675 (5) and 3.666 (2) A].

PMID- 22590328
TI  - A monoclinic polymorph of (R,R)-4,4'-dibromo-2,2'-[cyclo-hexane-1,2
      diylbis(nitrilo-methanylyl-idene)]diphenol.
AB  - The title compound, C(20)H(20)Br(2)N(2)O(2), a tetra-dentate Schiff base, is the
      enanti-omerically pure R,R-diastereomer of four possible stereoisomers. The mol
      ecular structure reveals two strong intra-molecular O-H?N hydrogen bonds between
      the hy-droxy O atom and the imino N atom, which each generate S(6) rings. In the
      crystal, mol-ecules are stacked in columns along the a axis; when viewed down the
      b axis, successive columns are stacked in the opposite direction. The structure
      reported herein is the monoclinic polymorph of the previously reported ortho-rhom
      bic form [Yi & Hu (2009 ?). Acta Cryst. E65, o2643], in which the complete mol
      ecule is generated by a crystallographic twofold axis.

PMID- 22590329
TI  - 5-Methyl-N-[2-(trifluoro-meth-yl)phen-yl]isoxazole-4-carboxamide.
AB  - In the title compound, C(12)H(9)F(3)N(2)O(2), the benzene ring is nearly
      perpendicular to the isoxazole ring, making a dihedral angle of 82.97 (2) degrees
      . In the crystal, mol-ecules are linked by N-H?O hydrogen bonds into a supra
      molecular chain running along the c axis.

PMID- 22590330
TI  - Absolute configuration of xerophenone A.
AB  - The title compound, C(33)H(42)O(5), known as xerophenone A {systematic name:
      (1R,3R,4R,6S,8E,10R)-10-hy-droxy-8-[hy-droxy(phen-yl)methyl-ene]-4-methyl-1,6-bis
      (3-methyl-but-2-en-1-yl)-3-(3-methyl-but-3-en-1-yl)-11-oxatricyclo
      [4.3.1.1(4,10)]undecane-7,9-dione} is a naturally occurring rearranged
      benzophenone compound which was isolated from the twigs of Garcinia propinqua.
      The absolute configuration was determined by refining the Flack parameter to 0.18
      (16). The absolute configurations at positions 1, 3, 4, 6 and 10 of the
      xerophenone A are R, R, R, S and R. In the mol-ecule, the cyclo-hexane-1,3-dione,
      tetra-hydro-2H-pyran and tetra-hydro-furan rings adopt twisted boat, standard
      chair and envelope conformations, respectively. The 3-methyl-but-3-en-1-yl
      substituent is disordered over two sets of sites in a 0.771 (11):0.229 (11)
      ratio. An intra-molecular O-H?O hydrogen bond generates an S(6) ring motif. In
      the crystal, mol-ecules are linked by O-H?O and weak C-H?O inter-actions into a
      chain along the a axis. A very weak C-H?pi inter-action and C?O short contact
      [2.989 (2) A] are also present.

PMID- 22590331
TI  - Tizoxanide pyridine monosolvate.
AB  - IN THE TITLE COMPOUND [SYSTEMATIC NAME: 2-hy-droxy-N-(5-nitro-1,3-thia-zol-2
      yl)benzamide pyridine monosolvate], C(10)H(7)N(3)O(4)S.C(5)H(5)N, the dihedral
      angle between the pyridine and benzamide rings is 80.55 (7) degrees . An
      intamolecular O-H?N hydrogen bond occurs in the tizoxanide. In the crystal, the
      components are linked by an O-H?N hydrogen bond, forming a zigzag chain along the
      c axis. Aromatic pi-pi inter-actions between inversion-related pyridine rings
      [centroid-centroid distance = 3.803 (6) A] are also observed.

PMID- 22590332
TI  - N'-(2,6-Dichloro-benzyl-idene)furan-2-carbohydrazide.
AB  - In the title compound, C(12)H(8)Cl(2)N(2)O(2), the dihedral angle between the
      furan and benzene rings is 72.90 (16) degrees . In the crystal, mol-ecules are
      linked by N-H?O hydrogen bonds, generating C(4) chains propagating in [100].

PMID- 22590333
TI  - (Z)-1,3-Bis(4-chloro-phen-yl)-2-(1H-1,2,4-triazol-1-yl)prop-2-en-1-one.
AB  - In the title mol-ecule, C(17)H(11)Cl(2)N(3)O, the C=C bond connecting the
      triazole and 4-chloro-phenyl groups adopts a Z geometry. The dihedral angles
      formed by the triazole ring and the 4-chloro substituted benzene rings are 67.3
      (1) and 59.1 (1) degrees . The dihedral angle between the two benzene rings is
      73.5 (1) degrees .

PMID- 22590334
TI  - Ethyl 2-benzoyl-6-methyl-indolizine-7-carboxyl-ate.
AB  - The title compound, C(19)H(17)NO(3), was synthesized using a tandem annulation
      reaction between 4-benzoyl-1H-pyrrole-2-carbaldehyde and (E)-ethyl 4-bromo-but-2
      enoate under mild conditions. The dihedral angle between the benzene ring and the
      indolizine ring system is 41.73 (4) degrees .

PMID- 22590335
TI  - (E)-3,3',4,4',7,7',8,8'-Octa-methyl-2H,2'H-1,1'-bi(cyclo-penta-[fg]acenaphthyl
      enyl-idene)-2,2',5,5',6,6'-hexa-one dichloro-methane monosolvate.
AB  - The title compound, C(36)H(24)O(6).CH(2)Cl(2), is a dimer of two essentially
      planar (r.m.s., deviations of fitted plane of 14 pyracene C atoms = 0.0539 and
      0.0543 A) tetra-cyclic pyracene frameworks (each with four methyl groups and
      three carbonyl groups on the peripheral carbon atoms) twisted along a central C=C
      bond with an angle of 50.78 (3) degrees  at 90 K. There are notably long Csp(2)
      Csp(2) bonds associated with the carbonyl groups, the longest being 1.601 (3) A
      between two carbonyl C atoms. There are also intermolecular carbonyl?carbonyl
      interactions of both parallel and antiparallel types, with C?O distances in the
      range 3.041 (3) to 3.431 (2) A. This compound is of inter-est with respect to the
      synthesis of fullerene fragments, such as corannulene and
      semibuckminsterfullerene derivatives (or 'buckybowls'), and is a side product of
      the previously reported oxidation reaction. Structural details, such as planarity
      analysis of fused rings, out-of-plane deviation of substituents, inter-molecular
      inter-actions, and longer than typical bond lengths, will be discussed as well as
      comparisons to structurally related compounds.

PMID- 22590336
TI  - 3,11-Dibromo-14-(4-chloro-phen-yl)-14H-dibenzo[a,j]xanthene dimethyl-formamide
      monosolvate.
AB  - In the title compound, C(27)H(15)Br(2)ClO.C(3)H(7)NO, the xanthene moiety has a
      flattened boat conformation with a folding angle between the naphthalene units of
      9.46 (3) degrees . The mean planes of the xanthene system and its 4-chloro-phenyl
      substituent are nearly perpendicular [dihedral angle = 89.43 (5) degrees ]. The
      dimethyl-formamide solvent mol-ecule is disordered over two sets of sites with an
      occupancy ratio of 0.520 (11):0.480 (11).

PMID- 22590337
TI  - 1-{(E)-[4-(4-Meth-oxy-phen-yl)butan-2-yl-idene]amino}-3-methyl-thio-urea.
AB  - Two independent mol-ecules comprise the asymmetric unit of the title compound,
      C(13)H(19)N(3)OS, which differ in the conformations of the residues linking the
      thio-urea and the terminal benzene ring, as manifested in the C(m)-C(m)-C(a)-C(a)
      torsion angles [78.03 (16) and -93.64 (16) degrees , respectively; m = methyl-ene
      and a = aromatic]. The dihedral angles [84.40 (4) and 88.28 (5) degrees ] formed
      between the thio-urea residue and the benzene ring indicate an almost orthogonal
      relationship. In each thio-urea residue, the N-H hydrogen atoms are anti, and the
      terminal N-H hydrogen atom forms an intra-molecular N-H?N hydrogen bond with the
      imine-N atom. In each case, the conformation about the imine C=N double bond
      [1.2812 (17) and 1.2801 (17) A] is E. In the crystal, the mol-ecules are
      connected by N-H?S hydrogen bonds and these are connected into four mol-ecule
      aggregates via N-H?O hydrogen bonds, which are assembled into a two-dimensional
      array parallel to (011) via C-H?pi and pi-pi inter-actions [ring centroid
      centroid distance = 3.8344 (9) A].

PMID- 22590338
TI  - 2,4,6-Tris(2,4-dimethyl-phen-yl)-1,3,5-triazine.
AB  - Two virtually superimposable mol-ecules comprise the asymmetric unit of the title
      compound, C(27)H(27)N(3). The range of dihedral angles between the central 1,3,5
      triazine ring and the attached benzene rings is 20.88 (14)-31.36 (14) degrees ,
      and the shape of each mol-ecule is of a flattened bowl. The crystal packing
      features weak C-H?pi bonds and pi-pi inter-actions between triazine and benzene
      rings [centroid-centroid separations = 3.7696 (17) and 3.7800 (18) A] that result
      in the formation of supra-molecular layers in the ac plane. The crystal studied
      was a non-merohedral twin with a minor twin component of 20.7 (3)%.

PMID- 22590339
TI  - (2E)-1-(2,4-Dichloro-phen-yl)-3-(3,4,5-trimeth-oxy-phen-yl)prop-2-en-1-one.
AB  - In the title compound, C(18)H(16)Cl(2)O(4), the dihedral angle between the
      benzene rings is 82.40 (4) degrees . The meth-oxy groups at both meta positions
      of the 3,4,5-trimeth-oxy-phenyl ring are slightly twisted from the aromatic ring
      [C-O-C-C = -166.60 (8) and -6.18 (13) degrees ], whereas the meth-oxy group at
      the para position is almost perpendicular [C-O-C-C = 112.08 (9) degrees ]. The
      ketone O atom is connected to the 2,4-dichloro-phenyl group through a C(ar)-C(ar)
      C-O (ar = aromatic) torsion angle of -116.43 (9) degrees . In the crystal, mol
      ecules are linked by C-H?O hydrogen bonds into infinite chains along the b axis.
      The crystal structure also features C-H?pi inter-actions.

PMID- 22590340
TI  - 5-Chloro-4'-ethyl-3H-spiro-[1,3-benzo-thia-zole-2,1'-cyclo-hexa-ne].
AB  - In the title compound, C(14)H(18)ClNS, the 2,3-dihydro-1,3-thia-zole ring adopts
      an envelope with the S,N-bound C atom at the flap and the cyclo-hexane ring
      adopts a chair conformation. In the crystal, N-H?S hydrogen bonds with C(5)
      motifs connect the mol-ecules into chains parallel to the c axis.

PMID- 22590341
TI  - Methyl 5-bromo-2-hy-droxy-benzoate.
AB  - The title compound, C(8)H(7)BrO(3), is almost planar (r.m.s. deviation for the
      non-H atoms = 0.055 A). In the crystal, O-H?O hydrogen bonds link the mol-ecules
      into C(6) chains propagating in [010]. Very weak aromatic pi-pi inter-actions
      [centroid-centroid distances = 3.984 (5) and 3.982 (5) A] also occur.

PMID- 22590342
TI  - rac-3-exo-Ammonio-7-anti-carb-oxy-tricyclo-[2.2.1.0.(2,6)]heptane-3-endo-carboxyl
      ate monohydrate.
AB  - The racemic title compound, C(9)H(11)NO(4).H(2)O, a tricyclic rearranged amino
      norbornane dicarb-oxy-lic acid, is a conformationally rigid analogue of glutamic
      acid and exists as an ammonium-carboxyl-ate zwitterion, with the bridghead carb
      oxy-lic acid group anti-related. In the crystal, N-H?O and O-H?O hydrogen bonds
      involving the ammonium, carb-oxy-lic acid and water donor groups with both water
      and carboxyl O-atom acceptors give a three-dimensional framework structure.

PMID- 22590343
TI  - 5-Bromo-2-(3-fluoro-phen-yl)-3-methyl-sulfinyl-1-benzofuran.
AB  - In the title compound, C(15)H(10)BrFO(2)S, the 3-fluoro-phenyl ring makes a
      dihedral angle of 30.77 (6) degrees  with the mean plane [mean deviation = 0.014
      (1) A] of the benzofuran ring system. In the crystal, mol-ecules are linked by
      pairs of weak C-H?O hydrogen bonds into inversion dimers. A Br?O contact [3.214
      (1) A] is also observed.

PMID- 22590344
TI  - Alternariol 9-O-methyl ether.
AB  - The title compound (AME; systematic name: 3,7-dihy-droxy-9-meth-oxy-1-methyl-6H
      benzo[c]chromen-6-one), C(15)H(12)O(5), was isolated from an endophytic fungi
      Alternaria sp., from Catharanthus roseus (common name: Madagascar periwinkle).
      There is an intramolecular O-H?O hydrogen bond in the essentially planar mol
      ecule (r.m.s. deviation 0.02 A). In the crystal, the molecule forms an O-H?O
      hydrogen bond with its centrosymmetric counterpart with four bridging inter
      actions (two O-H?O and two C-H?O). The almost planar sheets of the dimeric units
      thus formed are stacked along b axis via C-H?pi and pi-pi contacts [with C?C
      short contacts between aromatic moieties of 3.324 (3), 3.296 (3) and 3.374 (3)
      A].

PMID- 22590345
TI  - 4-Methyl-N-p-tolyl-piperidine-1-carbox-amide.
AB  - In the title mol-ecule, C(14)H(20)N(2)O, the piperidine ring has a chair
      conformation and its N atom is close to planar (bond-angle sum = 357.5 degrees ).
      The dihedral angle between the amide group and the aromatic ring is 47.43 (19)
      degrees . In the crystal, mol-ecules are linked into [100] C(4) chains by N-H?O
      hydrogen bonds.

PMID- 22590346
TI  - (1-Oxo-2,6,7-trioxa-1-phosphabicyclo-[2.2.2]octan-4-yl)methyl 4-methyl-benzene
      sulfonate.
AB  - In the title compound, C(12)H(15)O(7)PS, the P atom has a distorted tetra-hedral
      environment. The P-O-C-C torsion angles deviate significantly from zero [average
      = 12.0 (3) degrees ], indicating that the bicyclic OP(OCH(2))(3)C cage is
      strained. In the crystal, weak C-H?O inter-actions consolidate the packing.

PMID- 22590347
TI  - 2-N-Benzyl-2,6-dide-oxy-2,6-imino-3,4-O-isopropyl-idene-3-C-methyl-d-allono
      nitrile.
AB  - X-ray crystallography firmly established the relative stereochemistry of the
      title compound, C(17)H(22)N(2)O(3). The absolute configuration was determined by
      use of 2-C-methyl-d-ribonolactone as the starting material. The compound exists
      as O-H?N hydrogen-bonded chains of mol-ecules running parallel to the a-axis.

PMID- 22590348
TI  - 2,4-Diamino-6-methyl-1,3,5-triazin-1-ium hydrogen oxalate.
AB  - The title compound, C(4)H(8)N(5) (+).C(2)HO(4) (-), was obtained from the
      reaction of oxalic acid and 2,4-diamino-6-methyl-1,3,5-triazine. The protonated
      triazine ring is essentially planar with a maximum deviation of 0.035 (1) A, but
      the hydrogen oxalate anion is less planar, with a maximum deviation of 0.131 (1)
      A for both carbonyl O atoms. In the crystal, the ions are linked by inter
      molecular N-H?O, N-H?N, O-H?O and C-H?O hydrogen bonds, forming a three
      dimensional network. Weak pi-pi [centroid-centroid distance = 3.763 A] and C-O?pi
      inter-actions [O?centroid = 3.5300 (16) A, C-O?centroid = 132.19 (10) degrees ]
      are also present.

PMID- 22590349
TI  - 5,5,7,12,14,14-Hexamethyl-1,8-diaza-4,11-diazo-niacyclo-tetra-deca-4,11-diene
      dichloride trihydrate.
AB  - In the title compound, C(16)H(34)N(4) (2+).2Cl(-).3H(2)O, the two protonated N
      atoms in the macrocyclic ring of the dication are located at diagonally opposite
      positions. There are two intramolecular N-H?N hydrogen bonds in the cation. The
      crystal structure features O-H?Cl, O-H?O, C-H?Cl and N-H?Cl hydrogen bonds.

PMID- 22590350
TI  - 1-Methyl-1,3-diazinan-2-one.
AB  - In the crystal structure of the title compound, C(5)H(10)N(2)O, mol-ecules are
      connected via pairs of strong N-H?O hydrogen bonds into centrosymmetric dimers,
      which are stacked along the a axis. The molecule is not planar, the dihedral
      angle between the N/C/N and C/C/C planes being 42.1(1) degrees .

PMID- 22590351
TI  - 3',6'-Bis(diethyl-amino)-2-[(E)-2-(4-hy-droxy-3-meth-oxy-benzyl-idene-amino)-eth
      yl]spiro-[isoindoline-1,9'-xanthen]-3-one ethanol monosolvate.
AB  - In the title compound, C(38)H(42)N(4)O(4).C(2)H(6)O, prepared via a spiro-lactam
      ring-formation reaction in a rhodamine dye, the xanthene ring system is
      approximately planar (r.m.s. deviation = 0.0014A) and subtends dihedral angles of
      88.10 (3) and 86.92 (4) degrees  with the spiro-lactam (r.m.s. deviations =
      0.0012 A) and benzene rings, respectively. The crystal structure consists of
      chains parallel to [-101], formed via O-H?O inter-actions.

PMID- 22590352
TI  - N-(4-Chloro-phen-yl)-4-meth-oxy-3-(propanamido)-benzamide cyclo-hexane
      hemisolvate.
AB  - The title compound, C(17)H(17)ClN(2)O(3).0.5C(6)H(12), was prepared by the
      condensation reaction of 4-meth-oxy-3-(propanamido)-benzoic acid with 4-chloro
      aniline. The Cl atom, the propionyl CH(3) group and the cyclo-hexyl CH(2) group
      are disordered over two sets of sites of equal occupancy in both mol-ecules. The
      cyclo-hexane solvent mol-ecule is disordered over two orientations which were
      modelled with relative occupancies of 0.484 (4) and 0.516 (4). In the crystal,
      there are a number of N-H?O hydrogen bonds, forming layers perpendicular to
      (001).

PMID- 22590353
TI  - 2,4,6,8-Tetra-kis(4-chloro-phen-yl)-3,7-diaza-bicyclo-[3.3.1]nonan-9-one O-benzyl
      oxime acetone monosolvate.
AB  - In the title compound, C(38)H(31)Cl(4)N(3)O.C(3)H(6)O, the 3,7-diaza-bicycle
      exists in a chair-boat conformation. The 4-chloro-phenyl groups attached to the
      chair form are equatorially oriented at an angle of 18.15 (3) degrees  with
      respect to each other, whereas the 4-chloro-phenyl groups attached to the boat
      form are oriented at an angle of 32.64 (3) degrees . In the crystal, mol-ecules
      are linked by N-H?pi and C-H?O inter-actions.

PMID- 22590354
TI  - (E)-Ethyl 2-cyano-3-(furan-2-yl)acrylate.
AB  - There are two independent mol-ecules in the asymmetric unit of the title
      compound, C(10)H(9)NO(3), in both of which, all non-H atoms except for the methyl
      C atom lie nearly in the same plane [maximum deviations = 0.094 (3) and 0.043 (2)
      A]. In the crystal, each independent mol-ecules is linked by pairs of C-H?O inter
      actions, generating inversion dimers with R(2) (2)(10) ring motifs.

PMID- 22590355
TI  - 6-Meth-oxy-1-(4-meth-oxy-phen-yl)-1,2,3,4-tetra-hydro-9H-beta-carbolin-2-ium
      acetate.
AB  - In the title compound, C(19)H(21)N(2)O(2) (+).C(2)H(3)O(2) (-), the 1H-indole
      ring system is essentially planar [maximum deviation = 0.0257 (14) A] and forms a
      dihedral angle of 87.92 (7) A with the benzene ring attached to the tetra-hydro
      pyridinium fragment. The tetra-hydro-pyridinium ring adopts a half-chair
      conformation. In the crystal, cations and anions are linked by inter-ionic N-H?O,
      C-H?O and C-H?N hydrogen bonds into chains along the a axis.

PMID- 22590356
TI  - N'-(2,6-Difluoro-benzyl-idene)pyridine-4-carbohydrazide.
AB  - In the title compound, C(13)H(9)F(2)N(3)O, the pyridine ring forms a dihedral
      angle of 16.92 (7) degrees  with the benzene ring. In the crystal, mol-ecules are
      linked via N-H?O, C-H?O and C-H?F, with the same O atom accepting two bonds.

PMID- 22590357
TI  - 1-(Biphenyl-4-ylcarbon-yl)-3-(2-chloro-4-nitro-phen-yl)thio-urea.
AB  - The benzene rings of the biphenyl group in the title compound,
      C(20)H(14)ClN(3)O(3)S, are nearly coplanar [maximum deviation = 0.20 (3) A]. The
      mean plane of the biphenyl group forms a dihedral angle of 5.24 (7) degrees  with
      the aromatic ring of the nitro-chloro-benzene group. Intra-molecular N-H?Cl, N
      H?O and C-H?S hydrogen bonds stabilize the cis-trans conformation of the mol
      ecule. In the crystal, mol-ecules are linked by C-H?O and C-H?S hydrogen bonds
      into mutually inter-woven corrugated layers parallel to (10-2).

PMID- 22590358
TI  - 1-Acetyl-oxymethyl-1,3,5,7-tetra-aza-adamantan-1-ium hexa-fluoro-phosphate.
AB  - In the crystal structure of the title salt, C(9)H(17)N(4)O(2) (+).PF(6) (-), the
      cations and anions are linked by weak C-H?F inter-actions while C-H?O inter
      actions also occur between the cations.

PMID- 22590359
TI  - 5-Nitro-2-trifluoro-methyl-1H-benzimidazole monohydrate.
AB  - In the crystal structure of the title compound, C(8)H(4)F(3)N(3)O(2).H(2)O, the
      main mol-ecule and the water mol-ecule are linked by an N-H?O hydrogen bond. O
      H?N, O-H?O and C-H?O hydrogen bonds further link the mol-ecules into sheets.

PMID- 22590360
TI  - Cyano-methyl 4-(4-methyl-benzene-sulfonamido)-benzoate.
AB  - The title mol-ecule, C(16)H(14)N(2)O(4)S, adopts an L-shaped conformation, with
      the central C-S-N-C torsion angle being -69.1 (3) degrees . The two benzene rings
      form a dihedral angle of 89.94 (15) degrees . The mol-ecular conformation may be
      influenced by a weak intra-molecular C-H?O hydrogen bond which generates an S(6)
      ring motif. In the crystal, mol-ecules are linked by N-H?O and weak C-H?O
      hydrogen bonds, forming chains propagating along the b axis. Weak C-H?N hydrogen
      bonds connect the chains into a two-dimensional network parallel to (011). The
      crystal studied was an inversion twin, the ratio of components being 0.7 (1):0.3
      (1).

PMID- 22590361
TI  - Bis(pyridinium) naphthalene-1,5-di-sulfonate dihydrate.
AB  - The asymmetric unit of the title organic salt, 2C(5)H(6)N(+).C(10)H(6)O(6)S(2) (2
      ).2H(2)O, consists of a pyridinium cation, half a naphthalene-1,5-disulfonate
      dianion and a water mol-ecule. The dianion has a crystallographically imposed
      centre of symmetry. In the crystal, N-H?O and O-H?O hydrogen bonds link cations,
      anions and water mol-ecules into a three-dimensional network.

PMID- 22590363
TI  - (1-Hy-droxy-ethyl-idene)(meth-yl)aza-nium bromide-N-methyl-acetamide (1/1).
AB  - The asymmetric unit of the organic hybrid salt, C(3)H(8)NO(+).Br(-).C(3)H(7)NO,
      comprises an N-methyl-acetamide cation, a N-methyl-acetamide mol-ecule and a
      bromide anion. The amide species are linked head-to-head through a short O?H?O
      hydrogen bond, giving a monocation, which is extended by N-H?Br hydrogen bonds
      into chains along the b-axis direction.

PMID- 22590362
TI  - Guanidinium chloride-18-crown-6 (2/1).
AB  - In the crystal of the title compound, 2CH(6)N(3) (+).2Cl(-).C(12)H(24)O(6), the
      18-crown-6 mol-ecule is located across an inversion center. The guanidinium
      cation links to the 18-crown-6 mol-ecule and chloride anion via N-H?O and N-H?Cl
      hydrogen bonds.

PMID- 22590364
TI  - 4-Methyl-benzoic acid-N'-[(E)-4-methyl-benzyl-idene]pyridine-4-carbohydrazide
      water (1/1/1).
AB  - In the title hydrated 1:1 adduct, C(8)H(8)O(2).C(14)H(13)N(3)O.H(2)O, the Schiff
      base mol-ecule exists in an E conformation with respect to the N=C bond [1.2843
      (13) A] and the dihedral angle between the pyridine ring and the benzene ring is
      1.04 (5) degrees . In the crystal, mol-ecules are linked by N-H?O, C-H?O, O-H?O
      and O-H?N hydrogen bonds into sheets lying parallel to the ab plane. The crystal
      structure also features pi-pi inter-actions with centroid-centroid distances of
      3.6224 (6) and 3.7121 (6) A.

PMID- 22590365
TI  - 2-Amino-3-carb-oxy-pyridinium chloride hemihydrate.
AB  - The asymmetric unit of the title compound, C(6)H(7)N(2)O(2) (+).Cl(-).0.5H(2)O,
      consists of two protonated 2-amino-3-carb-oxy-pyridine cations, two chloride
      anions and one mol-ecule of water. The crystal packing can be described as
      alternating layers of cations and anions parallel to (110), which are linked
      together by O(w)-H?Cl inter-actions. In the crystal, four types of classical
      hydrogen bonds are observed, viz. cation-anion (O-H?Cl and N-H?Cl), cation-cation
      (N-H?O), cation-water (N-H?O(w)) and water-anion (O(w)-H?Cl), resulting in the
      formation of an infinite three-dimensional network.

PMID- 22590366
TI  - N-(4-Bromo-phen-yl)-2-[(1-cyclo-hexyl-meth-yl-1H-1,2,4-triazol-3-yl)sulfanyl]
      acetamide.
AB  - The title compound, C(17)H(21)BrN(4)OS, was synthesized as a potential reverse
      transcriptase (RT) inhibitor of the human immunodeficiency virus type 1 (HIV-1).
      In the molecule, there is an N-H?S hydrogen bond making a five-membered ring. In
      the crystal, mol-ecules are connected into centrosymmetric dimers via pairs of N
      H?N and weak C-H?N hydrogen bonds. The crystal structure also features C-H?O
      inter-actions.

PMID- 22590367
TI  - Methyl (2E)-2-{[(2-methyl-quinolin-8-yl)-oxy]meth-yl}-3-(thio-phen-2-yl)acrylate.
AB  - In the mol-ecule of the title compound, C(19)H(17)NO(3)S, the dihedral angle
      formed by the quinoline ring system and the thio-phene ring is 83.15 (8) degrees
      . In the crystal, C-H?O hydrogen bonds link the mol-ecules into a C(8) chain
      running along the b axis. The packing of the mol-ecules is further influenced by
      C-H?pi inter-actions.

PMID- 22590368
TI  - 7-Chloro-4-(piperazin-1-yl)quinoline.
AB  - There are two mol-ecules in the asymmetric unit (Z' = 2) of the title compound,
      C(13)H(14)ClN(3), Each mol-ecule is linked by N-H?N hydrogen bonds to another of
      the same type in a chain in [110]. The crystal studied was a non-merohedral twin
      with components 0.622 (2) and 0.378 (2).

PMID- 22590369
TI  - 4,7-Dichloro-quinoline.
AB  - The two mol-ecules in the asymmetric unit of the title compound, C(9)H(5)Cl(2)N,
      are both essentially planar (r.m.s. deviations for all non-H atoms = 0.014 and
      0.026 A). There are no close C-H?Cl contacts.

PMID- 22590370
TI  - N-(3-Hy-droxy-phen-yl)nicotinamide.
AB  - In the title mol-ecule, C(12)H(10)N(2)O(2), the benzene and pyridine rings form a
      dihedral angle of 5.01 (8) degrees . The amide group is twisted by 33.54 (7)
      degrees  from the plane of the pyridine ring. In the crystal, mol-ecules are
      linked into centrosymmetric dimers via pairs of O-H?N hydrogen bonds. N-H?O
      hydrogen bonds further link dimers related into chains along the b axis.

PMID- 22590371
TI  - 2,4-Diiodo-3-nitro-anisole.
AB  - IN THE TITLE COMPOUND (SYSTEMATIC NAME: 1,3-diiodo-4-meth-oxy-2-nitro-benzene),
      C(7)H(5)I(2)NO(3), the dihedral angle between the benzene ring and the nitro
      group is 88.0 (3) degrees , and the methyl group lies almost in the same plane as
      the ring [deviation = 0.034 (6) A]. In the crystal, aromatic pi-pi stacking
      occurs between inversion-related rings [centroid-centroid separation = 3.865 (3)
      A and slippage = 0.642 A]. A possible weak C-I?pi inter-action occurs [I?pi =
      3.701 (2) A and C-I?pi = 130.18 (13) degrees ], but there are no significant
      inter-molecular I?I contacts.

PMID- 22590372
TI  - (E)-1-(2,4-Dimethyl-quinolin-3-yl)-3-(4-methyl-phen-yl)prop-2-en-1-one.
AB  - In the title compound, C(21)H(19)NO, there are two mol-ecules in the asymmetric
      unit (Z' = 2). There are pi-pi inter-actions between these two mol-ecules
      [centroid-centroid distance = 3.678 (2) A], as well as a weak C-H?O inter-action.
      The conformation adopted by the two mol-ecules is such that the quinoline mean
      plane and the benzene ring are almost perpendicular [89.04 (5) and 76.89 (4)
      degrees ]. In each mol-ecule, the methyl group of the tolyl ring is disordered
      over two conformations, with occupancy ratios of 0.56 (3):0.44 (3) and 0.65
      (3):0.35 (3).

PMID- 22590373
TI  - [2-(1H-Indol-4-yl)eth-yl]dipropyl-amine.
AB  - In the title compound, C(16)H(24)N(2), the aliphatic amine substituent is rotated
      almost orthogonally [C-C-C-C torsion angle = 75.7 (3) degrees ] out of the plane
      of the indole unit. The amine N atom has a pyramidal configuration deviating by
      0.380 (3) A from the plane of the adjacent C atoms. All of the aliphatic groups
      are in extended transoid conformations. In the crystal, mol-ecules form chains
      along the a axis via N-H?N hydrogen bonds.

PMID- 22590374
TI  - 1-(Anthracen-1-yl)pyrrolidine-2,5-dione.
AB  - In the mol-ecular structure of title compound, C(18)H(13)NO(2), the succinimide
      ring is orientated away from the plane of the anthracene moiety by 71.94 (4)
      degrees . The crystal structure features three different types of inter-molecular
      inter-actions, viz. C-H?O, C-H?pi and pi-pi bonds. Mol-ecules along the b axis
      stack on each other as a result of pi-pi inter-actions which have a centroid
      centroid distance of 3.6780 (15) A, while C-H?pi inter-actions are present
      between neigbouring stacks. Also, acting between the stacks are the C-H?O inter
      actions between the aromatic H atoms of the anthracene and the O atoms of the
      succinimide.

PMID- 22590375
TI  - 3-Benzyl-2H-chromen-2-one.
AB  - The title compound, C(16)H(12)O(2), is a coumarin which was isolated from stones
      of the Chinese traditional medicine Clausena lansium. The pyrone ring is almost
      planar, with a mean deviation of 0.0135 (4) A. The benzene ring (A) of the
      benzopyrone unit forms dihedral angles of 1.82 (5) and 72.86 (2) degrees  with
      the pyrone ring and the substituent benzene ring, respectively. The crystal
      structure is stabilized by weak pi-pi stacking inter-actions, with a minimum
      centroid-centroid distance between benzene rings of 3.6761 (7) A.

PMID- 22590376
TI  - 2-[6-(4-Bromo-phen-yl)imidazo[2,1-b][1,3]thia-zol-3-yl]-N-[8-(4-hy-droxy-phen-yl)
      2-methyl-3-oxo-1-thia-4-aza-spiro-[4.5]decan-4-yl]acetamide ethanol disolvate.
AB  - In the title compound, C(28)H(27)BrN(4)O(3)S(2).2C(2)H(6)O, the cyclo-hexane ring
      adopts a chair conformation. The imidazo[2,1-b][1,3]thia-zole ring system is
      essentially planar with a dihedral angle of 1.1 (2) degrees  between the thia
      zole and imidazole rings. The mean plane of this ring system makes dihedral
      angles of 8.11 (16) and 79.43 (17) degrees , respectively, with the bromo- and hy
      droxy-substituted benzene rings. In the 5-methyl-1,3-thia-zolidin-4-one group,
      the S atom, the methyl group and the ring C atoms bonded to them are disordered
      over two sets of sites with refined occupancies of 0.610 (19) and 0.390 (19). The
      crystal structure features N-H?O, O-H?O, O-H?N and C-H?O hydrogen bonds and C
      H?pi inter-actions. Furthermore, two weak pi-pi stacking inter-actions [centroid
      centroid distances = 3.967 (3) and 3.892 (2) A] are also observed.

PMID- 22590377
TI  - N-(3-Nitro-benzo-yl)benzene-sulfonamide.
AB  - In the title compound, C(13)H(10)N(2)O(5)S, the C=O bond in the -SO(2)-NH-CO-
      segment is anti to the meta-nitro group in the benzoyl ring, while the N-C bond
      has gauche torsions with respect to the S=O bonds. The molecule is twisted at the
      N atom with a dihedral angle of 79.9 (2) degrees  between the sulfonyl benzene
      ring and the -SO(2)-NH-CO- segment. Furthermore, the dihedral angle between the
      benzeneline rings is 86.9 (2) degrees . In the structure, the mol-ecules are
      linked into helical chains along the b axis via N-H?O hydrogen bonds.

PMID- 22590378
TI  - 11-(4-Meth-oxy-phen-yl)-3,3-dimethyl-2,3,4,5,10,11-hexa-hydro-1H
      dibenzo[b,e][1,4]diazepin-1-one monohydrate.
AB  - In the title compound, C(22)H(24)N(2)O(2).H(2)O, the co-crystallized water mol
      ecule inter-acts with the N and O atoms of the mol-ecule through O(w)-H?N, O(w)
      H?O(meth-yl) and N-H?O(w) hydrogen-bonding inter-actions. These hydrogen bonds,
      along with the inter-molecular N-H?O=C hydrogen-bonding inter-actions, connect
      the mol-ecules into a three-dimensional network. The dihedral angle between the
      two aromatic rings is 65.46 (10) degrees .

PMID- 22590379
TI  - (1Z,2E)-N'-{1-[2-(4-Bromo-phen-yl)hydrazin-1-yl-idene]-1-chloro-propan-2-yl
      idene}thio-phene-2-carbohydrazide.
AB  - In the title compound, C(14)H(12)BrClN(4)OS, the thienyl ring is disordered over
      two orientations with a site-occupancy ratio of 0.853 (2):0.147 (2). The mol
      ecule is roughly planar, with the dihedral angles between the thienyl and benzene
      rings being 6.24 (16) and 9.7 (11) degrees  for the major and minor components,
      respectively. The central fragment is almost planar [r.m.s. deviation = 0.0275
      (2) A for the ten non-H atoms]. The mean plane through this middle unit makes a
      dihedral angle of 2.71 (7) degrees  with the benzene ring, whereas these values
      are 4.46 (15) and 7.7 (11) degrees  for the major and minor components of the
      thienyl ring, respectively. In the crystal, mol-ecules are linked into dimers by
      pairs of N-H?O hydrogen bonds, forming R(2) (2)(8) ring motifs. These dimers are
      arranged into sheets parallel to the ac plane.

PMID- 22590380
TI  - (Z)-7-[2-(4-Bromo-phen-yl)hydrazin-1-yl-idene]-6-methyl-3-(pyridin-4-yl)-7H-1,2,4
      triazolo[3,4-b][1,3,4]thia-diazine.
AB  - In the asymmetric unit of the title compound, C(16)H(12)BrN(7)S, there are two
      crystallographically independent mol-ecules with similar conformations. Both mol
      ecules are slightly twisted; the central 1,2,4-triazolo[3,4-b]-1,3,4-thia-diazine
      ring system makes dihedral angles of 9.65 (15) and 13.29 (15) degrees  with the
      pyridine and benzene rings, respectively, in one mol-ecule, whereas the
      corresponding values in the other mol-ecule are 9.30 (15) and 4.84 (15) degrees .
      A weak intra-molecular C-H?N inter-action with an S(6) ring motif is observed in
      each mol-ecule. In the crystal, the independent mol-ecules are each linked
      through N-H?N hydrogen bonds and weak C-H?N interactions into ribbons along the c
      axis. The ribbons are further linked together by weak C-H?N, C-H?pi and pi-pi
      [centroid-centroid distances = 3.572 (2)-3.884 (2) A] inter-actions.

PMID- 22590381
TI  - 1,4-Dimethyl-piperazine-1,4-diium bis-(hexa-fluoro-phosphate) dihydrate.
AB  - In the title hydrated mol-ecular salt, C(6)H(16)N(2) (+).2PF(6) (-).2H(2)O, the
      complete 1,4-dimethyl-piperazine-1,4-diium dication is generated by
      crystallographic inversion symmetry and both C-N bonds are in equatorial
      orientations. In the crystal, the components are linked by O-H?F and N-H?O
      hydrogen bonds but there are no direct links between cations and anions.

PMID- 22590382
TI  - 3-(2,4-Dichloro-phen-yl)-5-(4-fluoro-phen-yl)-2-methyl-7-(trifluoro-meth
      yl)pyrazolo-[1,5-a]pyrimidine.
AB  - In the title compound, C(20)H(11)Cl(2)F(4)N(3), the central pyrazolo-[1,5
      a]pyrimidine unit is almost planar [the mean deviation from the best least-square
      plane through the nine atoms is 0.006 (2) A]. The fluoro-benzene ring is rotated
      out of this plane by 10.3 (3) degrees , whereas the dichloro-benzene ring is
      rotated by 46.2 (3) degrees . The crystal packing is dominated by Cl?Cl inter
      actions of 3.475 (3) A and van der Waals inter-actions.

PMID- 22590383
TI  - 3-(3,4-Dihydroxyphenyl)-1-methoxy-1-oxopropan-2-aminium chloride.
AB  - In the title compound, C(10)H(14)NO(4) (+).Cl(-), the benzene ring makes a
      dihedral angle of 64.68 (4) degrees  with the methyl-amino-propano-ate unit,
      which is bonded to the catechol ring via a methyl-ene C atom. A strong intra
      molecular O-H?O hydrogen bond occurs. In the crystal, O-H?O, N-H?Cl and O-H?Cl
      hydrogen bonds and weak C-H?O inter-actions link the mol-ecules into a three
      dimensional network.

PMID- 22590384
TI  - (E)-N'-[3-(4-Chloro-benzo-yloxy)benzyl-idene]pyridine-4-carbohydrazide acetic
      acid monosolvate monohydrate.
AB  - In the Schiff base mol-ecule of the title compound,
      C(20)H(14)ClN(3)O(3).CH(3)COOH.H(2)O, the central benzene ring makes dihedral
      angles of 36.26 (7) and 27.59 (8) degrees , respectively, with the terminal
      chloro-phenyl and pyridine rings. In the crystal, the three components are linked
      by O-H?O, N-H?O, O-H?N and C-H?O hydrogen bonds into a double-tape structure
      along the a axis.

PMID- 22590385
TI  - 2-Trifluoro-methyl-1H-benzimidazole.
AB  - The asymmetric unit of the title compound, C(8)H(5)F(3)N(2), consists of two half
      mol-ecules, one lies on a mirror plane and the other is generated by twofold
      rotation symmetry, with the axis running through the trifluoro-methyl C atom and
      the attached benzimidazole C atom. The two 2-trifluoro-methyl-1H-benzimidazole
      mol-ecules are connected by N-H?N hydrogen bonds involving the disordered NH H
      atoms into chains running parallel to the c axis. One of the trifluoro-methyl
      groups is disordered over two orientations of equal occupancy.

PMID- 22590386
TI  - (2E)-2-[(2-Hy-droxy-4-meth-oxy-phen-yl)(phen-yl)methyl-idene]-N-phenyl
      hydrazinecarboxamide dimethyl-formamide monosolvate.
AB  - The title compound, C(21)H(19)N(3)O(3).C(3)H(7)NO, adopts an E conformation with
      respect to the azomethine bond and crystallizes in the amide form. The dihedral
      angle between the rings lined to the C=N bond is 88.60 (12) degrees . The
      dimethyl-formamide solvent mol-ecule is disordered over two orientations with
      site occupancies of 0.684 (3) and 0.316 (3). The two N atoms of the
      hydrazinecarboxamide group are involved in inter-molecular N-H?O hydrogen bonds
      in which the dimethyl-formamide O atom acts as acceptor. The structure also
      features pi-pi inter-actions, with a centroid-centroid distance of 3.6561 (13) A.
      Classical and non-classical intra-molecular O-H?N and C-H?O hydrogen bonds are
      also present.

PMID- 22590387
TI  - (4-But-oxy-phen-yl)(1H-pyrrol-2-yl)methanone.
AB  - The asymmetric unit of the title compound, C(15)H(17)NO(2), contains two
      independent mol-ecules in which the dihedral angles between the pyrrole and
      benzene rings are 42.43 (9) and 45.70 (9) degrees . In both mol-ecules, the but
      oxy chains are disordered over two sets of sites, with occupancy ratios of 0.701
      (7):0.299 (7) and 0.869 (4):0.131 (4). Each mol-ecule forms a dimer with an
      inversion-related mol-ecule, through a pair of N-H?O hydrogen bonds. Weak C-H?O
      inter-actions link these dimers in the crystal structure.

PMID- 22590388
TI  - 2-[2-(Trifluoro-meth-yl)phen-yl]-2H-1-benzopyran-4(3H)-one.
AB  - In the title compound, C(16)H(11)F(3)O(2), the gamma-pyran-one ring adopts an
      envelope conformation with the chiral C atom standing out of the ring plane. In
      the crystal, molecules are linked by C-H?O and C-H?F inter-actions.

PMID- 22590389
TI  - 1-(Adamantan-1-yl)-3-(4-fluoro-phen-yl)thio-urea.
AB  - In the title mol-ecule, C(17)H(21)FN(2)S, the mean planes of the benzene ring and
      the thio-urea fragment form a dihedral angle of 61.93 (9) degrees . In the
      crystal, pairs of weak N-H?S inter-actions link the mol-ecules, forming inversion
      dimers.

PMID- 22590390
TI  - Bis(2-amino-pyridinium) 2,5-dicarb-oxy-benzene-1,4-dicarboxyl-ate.
AB  - In the title compound, 2C(5)H(7)N(2) (+).C(10)H(4)O(8) (2-), the 2-amino
      pyridinium (2-apyH) cation and 2,5-dicarb-oxy-benzene-1,4-dicarboxyl-ate (btcH2)
      anion are both nearly planar, with r.m.s. deviations of 0.015 and 0.050 A,
      respectively. The angle between the latter least-squares planes is 17.68 (9)
      degrees . The overall crystal structure results from the packing of two
      dimensional networks, formed by alternating 2-apyH and btcH2 linked by hydrogen
      bonds, parallel to (100).

PMID- 22590391
TI  - Ethyl 7-oxo-3,5-diphenyl-1,4-diazepane-2-carboxyl-ate.
AB  - The title compound, C(20)H(22)N(2)O(3), crystallizes with two independent mol
      ecules in the asymmetric unit. In both mol-ecules, the diazepane rings adopt
      chair conformations. The mean planes of the diazepane rings in the two molecules
      form dihedral angles of 71.6 (4)/40.3 (5) and 75.9 (5)/58.6 (7) degrees  with the
      neighbouring benzene rings. The carbonyl-group O atoms deviate significantly from
      the diazepane rings, by 0.685 (14) and 0.498 (13) A. The eth-oxy-carbonyl groups
      show conformational difference between two mol-ecules, as reflected in the
      orientation of the carbonyl O atoms and the C-C-O-C torsion angle of -179.0 (2)
      degrees  in one mol-ecule and 73.2 (2) degrees  in the other. In one molecule
      there is a short N-H?O contact that generates an S(5) ring motif. In the crystal,
      N-H?O inter-actions generate R(2) (2)(8) graph-set motifs and C-H?O inter-actions
      generate R(2) (2)(10) and R(2) (2)(14) graph-set motifs. C-H?pi inter-actions
      also occur.

PMID- 22590392
TI  - 2-Amino-4-nitro-phenol-1-(2,4,6-trihy-droxy-phen-yl)ethanone (1/1).
AB  - In the title compound, C(6)H(6)N(2)O(3).C(8)H(8)O(4), the 2-amino-4-nitro-phenol
      (ANP) and 1-(2,4,6-trihy-droxy-phen-yl)ethanone (THA) mol-ecules are both nearly
      planar, with r.m.s. deviations of 0.0630 and 0.0313 A, respectively. The angle
      between the least-squares planes of THA and ANP is 48.99 (2) degrees . In THA, an
      intra-molecular O-H?O hydrogen bond generates an S(6) ring motif. In the crystal,
      N-H?O, O-H?O and O-H?N hydrogen bonds lead to the formation of a three
      dimensional network. There are also inter-molecular pi-pi inter-actions between
      the benzene rings of ANP-ANP and of THA-THA mol-ecules, with centroid-centroid
      distances of 3.5313 (14) and 3.8440 (16) A, respectively. Weak C-O?pi and N-O?pi
      inter-actions also occur.

PMID- 22590393
TI  - Bis(1H-imidazol-3-ium) naphthalene-1,5-disulfonate.
AB  - The asymmetric unit of the title organic salt, 2C(3)H(5)N(2)
      (+).C(10)H(6)O(6)S(2) (2-), consists of an imidazolium cation and half a
      naphthalene-1,5-disulfonate dianion, completed to the full dianion through an
      inversion center. N-H?S and N-H?O hydrogen bonds link cations and anions in the
      crystal, forming a chain propagating along [101].

PMID- 22590394
TI  - Guanidinium bromide-18-crown-6 (2/1).
AB  - In the title compound, 2CH(6)N(3) (+).2Br(-).C(12)H(24)O(6), the 18-crown-6 mol
      ecule lies about an inversion center, whereas the guanidinium cation and bromide
      anion are in general positions. The guanidinium cations link with the bromide
      anions and the crown ether mol-ecules via N-H?O and N-H?Br hydrogen bonds, thus
      forming a three-dimensional network.

PMID- 22590395
TI  - 3-(2,4-Dichloro-phen-yl)-2-oxo-1-oxaspiro-[4.5]dec-3-en-4-yl 2-methyl-prop-2
      enoate.
AB  - In the title mol-ecule, C(19)H(18)Cl(2)O(4), the cyclo-hexane ring adopts a chair
      conformation. The furan ring is essentially planar and forms a dihedral angle of
      82.1 (1) degrees  with the benzene ring. In the crystal, weak C-H?O interactions
      are present.

PMID- 22590396
TI  - 2-Amino-6-(dimethyl-amino)pyridine-3,5-dicarbonitrile.
AB  - The title compound, C(9)H(9)N(5), is slightly twisted from planarity, with a
      maximum deviation of 0.0285 (13) A from the pyridine plane for the C atom bearing
      the amino group. The cyano groups are on different sides of the pyridine plane,
      with C- and N-atom deviations of 0.072 (3)/0.124 (4) and -0.228 (4)/-0.409 (5) A
      from the pyridine plane. In the crystal, N-H?N and C-H?N hydrogen bonds connect
      the mol-ecules into zigzag chains running along the c axis.

PMID- 22590397
TI  - Methyl 3-(2-hy-droxy-benzyl-idene)-2-methyl-dithio-carbazate.
AB  - In the title compound, C(10)H(12)N(2)OS(2), the thione and S-methyl groups are
      syn. An intra-molecular bifurcated O-H?(S,N) hydrogen bond occurs.

PMID- 22590398
TI  - Ethyl 2-(4-nitro-phen-oxy)acetate.
AB  - In the title mol-ecule, C(10)H(11)NO(5), the methyl C atom deviates by 0.830 (6)
      A from the mean plane of the remaining non-H atoms. In the crystal, weak C-H?O
      hydrogen bonds link the mol-ecules into layers parallel to the bc plane.

PMID- 22590399
TI  - 2-Hy-droxy-anilinium 3,5-dinitro-benzoate.
AB  - In the title molecular salt, C(6)H(8)NO(+).C(7)H(3)N(2)O(6) (-), which
      crystallizes in the chiral monoclinic space group P2(1), the achiral components
      assemble by three different N-H?O, one O-H?O and one C-H?O hydrogen bonds into
      two-stranded chains running parallel to [010]. The dihedral angles between the
      carboxy group and the two nitro groups and the mean plane of their attached
      benzene ring are 24.5 (9), 6.1 (6) and 13.0 (1) degrees , respectively..

PMID- 22590400
TI  - 1-(4-Chloro-butano-yl)-3-(2-chloro-phen-yl)thio-urea.
AB  - The asymmetric unit of the title compound, C(11)H(12)Cl(2)N(2)OS, contains two
      crystallographically independent mol-ecules with different conformations: the
      benzene ring and the thio-urea fragment form dihedral angles of 74.32 (11) and
      89.39 (11) degrees . One amino group in each mol-ecule is involved in intra
      molecular N-H?O and inter-molecular N-H?O hydrogen bonding: the latter links
      pairs of independent mol-ecules into dimers. In the crystal, weak N-H?S inter
      actions link these dimers into chains propagating along the c axis.

PMID- 22590401
TI  - Methyl 5-hy-droxy-3-phenyl-1,2-oxazolidine-5-carboxyl-ate.
AB  - In the title compound, C(11)H(13)NO(4), the isoxazolidine ring has an envelope
      conformation with the O atom as the flap. In the crystal, mol-ecules are liked
      via N-H?O and bifurcated O-H?(O,N) hydrogen bonds forming chains propagating
      along [010]. There are also C-H?O inter-actions present.

PMID- 22590402
TI  - (E)-3-(2-Chloro-phen-yl)-1-(4,4''-difluoro-5'-meth-oxy-1,1':3',1''-terphenyl-4'
      yl)prop-2-en-1-one.
AB  - The title compound, C(28)H(19)ClF(2)O(2), is a polysubstituted terphenyl
      derivative bearing a Michael system in which the C=C double bond has an E
      conformation. In the crystal, C-H?Cl and C-H?O contacts connect the mol-ecules
      into layers lying perpendicular to the a axis. The shortest inter-centroid
      distance between symmetry-related 4-fluoro-phenyl groups is 3.7547 (16) A.

PMID- 22590403
TI  - 2-Chloro-5-nitro-pyridin-4-amine.
AB  - The title mol-ecule, C(5)H(4)ClN(3)O(2), possesses mirror symmetry, with all of
      the atoms lying in the mirror plane. There is an intra-molecular N-H?O hydrogen
      bond involving the adjacent -NO(2) and -NH(2) groups. A short C-H?O inter-action
      is also observed. In the crystal, adjacent mol-ecules are linked via N-H?Cl and N
      H?N hydrogen bonds, forming chains propagating along [100].

PMID- 22590404
TI  - Butyl 4-(4-methyl-benzene-sulfonamido)-benzoate.
AB  - In the title compound, C(18)H(21)NO(4)S, the aromatic rings are almost normal to
      each other, with a dihedral angle of 89.27 (18) degrees . The mol-ecular
      conformation is stabilized by an intra-molecular C-H?O inter-action, which
      generates an S(6) motif. In the crystal, N-H?O and C-H?O hydrogen bonds lead to
      the formation of chains propagating along [010]. Neighbouring chains are linked
      via a C-H?pi inter-action. The -CH(2)CH(2)CH(3) atoms of the butyl group are
      disordered over two sets of sites, with a refined site-occupancy ratio of 0.536
      (16):0.464 (16).

PMID- 22590405
TI  - 4'-tert-Butyl-5-chloro-3H-spiro-[1,3-benzothia-zole-2,1'-cyclo-hexa-ne].
AB  - In the title compound, C(16)H(22)ClNS, the nine-membered 2,3-dihydro-1,3
      benzothia-zole ring system is essentially planar, with a maximum deviation of
      0.025 (2) A for the N atom. Its plane is almost perpendicular to the main plane
      of the substituted cyclo-hexane ring, which adopts a chair conformation. In the
      crystal, the molecules are linked by C-H?pi inter-actions.

PMID- 22590406
TI  - 1,4-Bis[4-(tert-butyl-sulfan-yl)phen-yl]buta-1,3-diyne.
AB  - The asymmetric unit of the title compound, C(24)H(26)S(2), consits of one half
      mol-ecule, which is located on a center of inversion. The two benzene rings are
      exactly coplanar while the tert-butyl group is oriented nearly perpendicular to
      the ring plane [C-S-C-C = -81.14 (11) degrees ].

PMID- 22590407
TI  - 3-Anilinomethyl-5-chloro-1,3--benzoxazol-2(3H)-one.
AB  - In the title compound, C(14)H(11)ClN(2)O(2), the 2,3-dihydro-1,3-benzoxazole ring
      system is essentially planar [maximum deviation = 0.009 (2) A] and makes a
      dihedral angle of 79.15 (7) degrees  with the phenyl ring. Inter-molecular N-H?O
      and weak C-H?Cl hydrogen bonds occur in the crystal structure.

PMID- 22590408
TI  - (E)-4-Amino-N'-(5-chloro-2-hy-droxy-benzyl-idene)benzohydrazide.
AB  - The title compound, C(14)H(12)ClN(3)O(2), displays an E conformation with respect
      to the C=N double bond. The dihedral angle between the benzene rings is 41.3 (5)
      degrees . The mol-ecular structure is stabilized by an intra-molecular O-H?N
      hydrogen bond. In the crystal, N-H?O and weak N-H?Cl hydrogen bonds link the mol
      ecules into a three-dimensional architecture. In addition, there are weak C-H?pi
      stacking inter-actions.

PMID- 22590409
TI  - 2-Chloro-3-[(E)-(hydrazin-1-yl-idene)meth-yl]-6-meth-oxy-quinoline.
AB  - In the title compound, C(11)H(10)ClN(3)O, the quinoline ring system is
      essentially planar, the r.m.s. deviation for the non-H atoms being 0.014 (2) A
      with a maximum deviation from the mean plane of 0.0206 (14) A for the C atom
      bonded to the -CH-N=NH(2) group. In the crystal, molecules are linked via N-H?O
      and N-H?N hydrogen bonds, forming zigzag layers parallel to (010).

PMID- 22590411
TI  - Bis(N-methyl-N-phenyl-carbamo-yl)disulfane.
AB  - The title compound, C(16)H(16)N(2)O(2)S(2), has been synthesized by several
      different high-yield routes, and has been encountered as a co-product in a number
      of reaction pathways, ever since it became of inter-est to our research program
      over 30 years ago. We now confirm the proposed mol-ecular structure in which the
      mol-ecule exhibits a twofold axis of symmetry through the mid-point of the S-S
      bond and the two planes defined by the (carbamo-yl)sulfenyl moieties are
      essentially perpendicular to each other [dihedral angle = 81.55 (14) degrees ].

PMID- 22590412
TI  - 1-Phenylethane-1,2-diyl 1,1'-biphenyl-2,2'-dicarboxylate.
AB  - In the title compound, C(22)H(16)O(4), the 7-phenyl ring is inclined at dihedral
      angles of 36.73 (9) and 69.37 (9) degrees  with respect to the biphenyl benzene
      rings. The two benzene rings of the biphenyl unit form a dihedral angle of 55.99
      (8) degrees . There are no significant hydrogen bonds observed in the crystal of
      this compound.

PMID- 22590410
TI  - Tri-tert-butyl-phospho-nium hy-droxy-tris-(penta-fluoro-phen-yl)borate.
AB  - The ionic title compound, C(12)H(28)P(+).C(18)HBF(15)O(-), was obtained by the
      stoichiometric reaction of (t)Bu(3)P, B(C(6)F(5))(3) and water in toluene. A weak
      P-H?O hydrogen bond is observed in the crystal structure.

PMID- 22590413
TI  - 1-(2-Bromophenyl)ethane-1,2-diyl 1,1'-biphenyl-2,2'-dicarboxylate.
AB  - In the title compound, C(22)H(15)BrO(4), the bromo-benzene ring is inclined at
      dihedral angles of 23.87 (11) and 52.37 (11) degrees  with respect to the planes
      of the two benzene rings. The two benzene rings of the biphenyl unit form a
      dihedral angle of 49.08 (11) degrees . In the crystal, mol-ecules are linked into
      [100] chains by C-H?O hydrogen bonds.

PMID- 22590414
TI  - 1,4-Bis[4-(meth-oxy-carbon-yl)benz-yl]-1H-1,2,4-triazol-4-ium bromide.
AB  - In the title salt, C(20)H(20)N(3)O(4) (+).Br(-), the dihedral angle between the
      benzene rings is 8.69 (16) degrees , and those between the benzene rings and the
      triazole ring are 69.98 (18) and 72.17 (18) degrees . In the crystal, C-H?Br
      hydrogen bonds link the cations and anions into chains along the c axis.

PMID- 22590415
TI  - Diethyl [(2-bromo-anilino)(1,3-diphenyl-1H-pyrazol-4-yl)meth-yl]phospho-nate.
AB  - In the title compound, C(26)H(27)BrN(3)O(3)P, the central pyrazole ring forms a
      dihedral angle of 71.7 (2) degrees  with the bromo-phenyl ring. In the crystal,
      mol-ecules are linked by pairs of N-H?O hydrogen bonds, forming inversion dimers
      with R(2) (2)(10) ring motifs. Four C atoms of the 3-phenyl ring are disordered
      over two sets of sites [site occupancies = 0.745 (6) and 0.225 (6)].

PMID- 22590416
TI  - Ethyl 3-acetyl-4-(3-meth-oxy-phen-yl)-6-methyl-2-sulfanyl-idene-1,2,3,4-tetra
      hydro-pyrimidine-5-carboxyl-ate.
AB  - In the title compound, C(17)H(20)N(2)O(4)S, the aryl ring is positioned
      perpendicular to the dihydro-pyrimidine ring, the dihedral angle between the ring
      planes being 77.48 (9) degrees . The carboxyl-ate and methyl groups are in a cis
      conformation with respect to the C=C bond. The dihydro-pyrimidine ring adopts a
      twist-boat conformation. The crystal structure is stabilized by N-H?O and C-H?O
      inter-actions, the former resulting in mol-ecular chains along the b axis and the
      latter forming inversion dimers.

PMID- 22590417
TI  - 3',6'-Bis(ethyl-amino)-2',7'-dimethyl-2-{2-(E)-[(thio-phen-2-yl)methyl-idene
      amino]-eth-yl}spiro-[isoindoline-1,9'-xanthen]-3-one methanol monosolvate.
AB  - The title compound, C(33)H(34)N(4)O(2)S.CH(3)OH, was prepared as a spiro-lactam
      ring formation of rhodamine 6 G dye for comparison with a ring-opened form. The
      xanthene and spiro-lactam rings are approximately planar [r.m.s. deviations from
      planarity = 0.122 (3) and 0.072 (6) A, respectively]. The dihedral angles formed
      by the spiro-lactam and thio-phene rings with the xanthene ring system are 89.7
      (6) and 86.5 (2) degrees , respectively. The crystal structure features N-H?O and
      C-H?O hydrogen bonds.

PMID- 22590419
TI  - Dimethyl 1-(3-hy-droxy-2-iodo-1-phenyl-prop-yl)-1H-1,2,3-triazole-4,5-dicarboxyl
      ate.
AB  - In the title compound, C(15)H(16)IN(3)O(5), the central triazole ring is
      essentially planar (r.m.s deviation = 0.0034 A) and makes a dihedral angle of
      70.14 (5) degrees  with the pendant benzene ring. The mean planes of the two meth
      oxy-carbonyl groups make dihedral angles of 22.52 (7) and 40.93 (4) degrees  with
      the triazole ring. In the crystal, inversion dimers linked by pairs of O-H?O
      hydrogen bonds generate R(2) (2)(18) loops. The dimers are linked by C-H?O and C
      H?N inter-actions into sheets lying parallel to the ac plane.

PMID- 22590418
TI  - (E)-2-[2-(4-Chloro-benzyl-idene)hydrazin-1-yl]-4-{[3-(dimethyl-aza-nium-yl)prop
      yl]amino}-quinazolin-1-ium bis-(perchlorate).
AB  - In the title compound, C(20)H(25)ClN(6) (2+).2ClO(4) (-), the organic cation is
      roughly planar, as shown by the dihedral angle of 3.78 (3) degrees  between the
      quinazoline and chloro-phenyl rings. The quinazoline ring is itself approximately
      planar, with an average deviation of 0.018 (4) A. The organic cation adopts an E
      configuration with respect to the C= N double bond of the hyrazinyl group. The
      (dimethyl-aza-nium-yl)propyl-amino side chain is disordered over two sets of
      sites with occupancies of 0.768 (10) and 0.232 (10). In the crystal, two cations
      and four anions are linked by strong N-H?O hydrogen bonds. Weak C-H?O hydrogen
      bonds exist among these aggregates.

PMID- 22590420
TI  - (2E)-1-(4,4''-Difluoro-5'-meth-oxy-1,1':3',1''-terphenyl-4'-yl)-3-(2,6-difluoro
      phen-yl)prop-2-en-1-one.
AB  - In the title compound, C(28)H(18)F(4)O(2), the central benzene ring makes
      dihedral angles of 44.27 (6), 56.33 (5) and 77.27 (6) degrees  with the two
      adjacent fluoro-benzene rings and terminal difluoro-substituted benzene ring,
      respectively. The dihedral angle between the fluoro-benzene rings is 87.81 (6)
      degrees . The meth-oxy and prop-2-en-1-one groups are essentially coplanar with
      their attached benzene rings, as indicated by their C-O-C(ar)-C(ar) [-0.06 (15)
      degrees ] and C-C-C(ar)-C(ar) [4.5 (2) degrees ] (ar = aromatic) torsion angles.
      In the crystal, mol-ecules are linked by C-H?F and C-H?O hydrogen bonds into
      sheets lying parallel to the ac plane. The crystal structure also features C-H?pi
      inter-actions.

PMID- 22590421
TI  - 2-[1-({2-[1-(2-Hy-droxy-5-{[meth-yl(phen-yl)amino]-meth-yl}phen-yl)ethyl-idene
      amino]-eth-yl}imino)-eth-yl]-4-{[meth-yl(phen-yl)amino]-meth-yl}phenol.
AB  - Mol-ecules of the title compound, C(34)H(38)N(4)O(2), lie across crystallographic
      inversion centres. The crystal packing can be described by alternating zigzag
      chains along the c axis in which the molecules are linked by van der Waals
      interactions. There is an intra-molecular O-H?N hydrogen bond and the two benzene
      rings in the asymmetric unit make a dihedral angle of 79.81 (6) degrees .

PMID- 22590422
TI  - Methyl (2E)-2-({2-[(2E)-2-benzyl-idene-3-meth-oxy-3-oxoprop-yl]-1,3-dioxoindan-2
      yl}meth-yl)-3-phenyl-prop-2-enoate.
AB  - In the title compound, C(31)H(26)O(6), the five-membered ring of the indane unit
      adopts a slight envelope conformation with the flap atom displaced by 1.38 (14)
      A. The mol-ecular conformation is stabilized by an intra-molecular C-H?O hydrogen
      bond, which generates an S(9) ring motif. In the crystal, pairs of C-H?O hydrogen
      bonds link centrosymmetrically related mol-ecules into dimers, generating R(2)
      (2)(22) ring motifs. The crystal packing is further stabilized by C-H?pi inter
      actions.

PMID- 22590423
TI  - N-(2,6-Diisopropyl-phen-yl)formamide toluene 0.33-solvate.
AB  - The crystal packing of the title compound, C(13)H(19)NO.0.33C(7)H(8), shows a
      channel at [001], which contains grossly disordered toluene solvent mol-ecules.
      The angle between the benzene ring and the mean plane of the formamide group is
      71.1 (1) degrees . The amide groups of neighbouring mol-ecules are connected by N
      H?O hydrogen bonds, forming 2(1) helical chains propagating along [001]. Mol
      ecules are also connected by weak inter-molecular C-H?O hydrogen bonds, forming
      6(1) helices.

PMID- 22590424
TI  - (6-Meth-oxy-2-oxo-2H-chromen-4-yl)methyl pyrrolidine-1-carbodithio-ate.
AB  - In the title compound, C(16)H(17)NO(3)S(2), the 2H-chromene ring is close to
      being planar [maximum deviation = 0.034 (2) A] and the pyrrolidine ring is
      twisted about the C-C bond opposite the N atom. The dihedral angle between the
      ring-system planes is 75.24 (16) degrees  and an intra-molecular C-H?S inter
      action occurs. In the crystal, mol-ecules are linked by C-H?O hydrogen bonds and
      the packing also exhibits pi-pi inter-actions, with a distance of 3.6106 (13) A
      between the centroids of the benzene rings of neighbouring mol-ecules.

PMID- 22590425
TI  - 4-(2,3-Dimeth-oxy-phen-yl)-1H-pyrrole-3-carbonitrile.
AB  - The asymmetric unit of the title compound, C(13)H(12)N(2)O(2), obtained in a
      search for analogs of the fungicide fludioxonil [systematic name: 4-(2,2-difluoro
      1,3-benzodioxol-4-yl)-1H-pyrrole-3-carbonitrile], contains two independent mol
      ecules, A and B. The benzene and pyrrole rings are inclined to each other at 38.5
      (1) and 29.3 (1) degrees  in mol-ecules A and B, respectively. In the crystal,
      bifurcated N-H?(O,O) hydrogen bonds link A mol-ecules into chains along [001],
      while B mol-ecules are linked into layers parallel to the bc plane via bifurcated
      N-H?(N,N) hydrogen bonds.

PMID- 22590426
TI  - Bis(4-meth-oxy-pyridin-3-yl)diazene.
AB  - The asymmetric unit of the title compound, C(12)H(12)N(4)O(2), consists of one
      half-mol-ecule, which is located on a center of inversion. The molecule has a
      step-like shape; the azo group adopting a trans configuration, with the pyridine
      rings being parallel-displace.

PMID- 22590427
TI  - 25,26-Bis(propan-2-yl-idene)hepta
      cyclo[20.2.1.1(10,13).0(2,21).0(3,8).0(9,14).0(15,20)]hexa-cosa
      2(21),3,5,7,9(14),11,15,17,19,23-deca-ene.
AB  - In the title compound, C(32)H(28), the central cyclo-octa-tetra-ene ring has a
      boat conformation, and the mol-ecule is saddle shaped. The seat is defined by the
      mean plane of the four-atom attachment points (r.m.s. deviation = 0.014 A) of the
      two bicyclo-heptenyl substituents. These substituents comprise the pommel and
      cantle, with each mean plane defined by four atoms proximate to the seat (r.m.s.
      deviations = 0.002 and 0.004 A). Relative to the seat, the pommel and cantle bend
      up 31.16 (4) and 29.40 (5) degrees , while the benzo units (flaps, r.m.s.
      deviations = 0.006 and 0.009 A) bend down 36.75 (4) and 38.46 (4) degrees . The
      mean planes of the dimethyl-ethyl-idene units are almost perpendicular to the
      saddle seat, making dihedral angles 86.89 (4) and 88.01 (4) degrees .

PMID- 22590428
TI  - (1S,2E,6R,7aR)-1,6-Dihy-droxy-2-(4-nitro-benzyl-idene)-2,3,5,6,7,7a-hexa-hydro-1H
      pyrrolizin-3-one.
AB  - The crystal structure of the title compound, C(14)H(14)N(2)O(5), contains two
      distinct conformers in the asymmetric unit. The compound has three defined
      stereocenters, two of them contiguous, and a C=C double bond with an E
      conformation. The stereocenters exhibit the same chirality in both conformers,
      with significant differences in the conformation of the five-membered rings of
      the pyrrolizine unit (both either in a twist or in an envelope form) and in the
      dihedral angles between the corresponding mean planes and the benzene rings. A
      prominent feature is a change from almost coplanar rings in one conformer to a
      new conformation in the second conformer, in which the mean plane of a five
      membered ring is almost perpendicular to the benzene ring, with a dihedral angle
      87.19 (8) degrees ; the corresponding angle in the first conformer is 14.02 (10)
      degrees . In the crystal, molecules are linked by O-H?O and C-H?O hydrogen bonds.
      Crystallographic data were essential to confirm the configuration of the double
      bond, which was unclear from the available two-dimensional NMR data. In addition,
      reliable Flack and Hooft parameters were obtained, allowing for the correct
      absolute structure to be determined.

PMID- 22590429
TI  - (1S,2E,6R,7aR)-2-Benzyl-idene-1,6-dihy-droxy-2,3,5,6,7,7a-hexa-hydro-1H
      pyrrolizin-3-one.
AB  - In the title compound, C(14)H(15)NO(3), the conformation of the double bond was
      determined to be E, confirming the result obtained from two-dimensional NMR data.
      The five-membered rings of the pyrrolizine unit exhibit C-envelope conformations,
      with C atoms displaced from the mean planes formed by the remaining rings atoms
      by 0.1468 (15) and 0.5405 (17) A. The mean planes of these rings (through all
      ring atoms) have a dihedral angle of 49.03 (10) degrees . In the crystal, mol
      ecules are linked by O-H?O hydrogen bonds. The absolute configuration of the mol
      ecule was established, as judged by the, as judged by the obtained values for the
      Hooft and Flack parameters.

PMID- 22590430
TI  - 4-[4-(4-Amino-1,2,5-oxadiazol-3-yl)-1,2,5-oxadiazol-3-yl]-1,2,5-oxadiazol-3
      amine.
AB  - The complete molecule of the compound, C(6)H(4)N(8)O(3), is generated by a
      crystallographic twofold rotation axis that runs through the central ring. The
      flanking ring is twisted by 20.2 (1) degrees  with respect to the central ring.
      One of the amino H atoms forms an intra-molecular N-H?N hydrogen bond; adjacent
      mol-ecules are linked by N-H?N hydrogen bonds forming a chain running along [10
      2].

PMID- 22590431
TI  - Benzene-1,2-di(aminium) naphthalene-1,5-disulfonate methanol monosolvate
      trihydrate.
AB  - In the title salt, C(6)H(10)N(2) (2+).C(10)H(6)O(6)S(2) (2-).CH(3)OH.3H(2)O, the
      cation lies on a mirror plane and the anion on a center of inversion. One lattice
      water mol-ecule is located on a mirror plane, another is equally disordered over
      two sites. The methanol solvent mol-ecule is disordered about a mirror plane. In
      the crystal, the cations, anions, water and methanol mol-ecules are linked by O
      H?O and N-H?O hydrogen bonds, forming a three-dimensional network.

PMID- 22590432
TI  - Bis(3-amino-propan-1-aminium) naphthalene-1,5-disulfonate dihydrate.
AB  - In the title hydrated salt, 2C(3)H(11)N(2) (+).C(10)H(6)O(6)S(2) (2-).2H(2)O, the
      anion lies on a center of inversion; its sulfonate -SO(3) group features one S-O
      bond that is longer than the other two. The O atom of this longer bond is the
      hydrogen-bond acceptor to the amino H atom of one cation and the ammonium H atom
      of another cation. In the crystal, N-H?O and O-H?O hydrogen bonds link the
      cations, anions and water mol-ecules into a three-dimensional network.

PMID- 22590433
TI  - (+/-)-trans-5-Benzoyl-2-(1H-indol-3-yl)-4-phenyl-4,5-dihydro-furan-3
      carbonitrile.
AB  - The furan ring in the title compound, C(26)H(18)N(2)O(2), is twisted about the
      C(H)-C(H) bond. The mol-ecular structure is stabilized by an intra-molecular C
      H?O inter-action, which generates an S(6) ring motif. The presence of N-H?N
      hydrogen bonds leads to inversion dimers, which are stabilized in the crystal
      packing by C-H?O and C-H?pi inter-actions, forming layers that stack along the a
      axis.

PMID- 22590434
TI  - (3S)-14,16-Dihy-droxy-3-methyl-3,4,5,6,9,10,11,12-octa-hydro-1H-2-benzoxacyclo
      tetra-decine-1,7(8H)-dione (zearalanone) monohydrate.
AB  - The absolute configuration of the title compound, C(18)H(24)O(5).H(2)O, was not
      been determined by anomalous-dispersion effects, but has been assigned by
      reference to an unchanging chiral centre in the synthetic procedure. Intra
      molecular O-H?O hydrogen bonds stabilize the mol-ecular conformation. In the
      crystal, O-H?O hydrogen bonds link the main mol-ecules and the water mol-ecules,
      forming an infinite three-dimensional network.

PMID- 22590435
TI  - N-(2-Nitro-phenyl-carbamothio-yl)acetamide.
AB  - In the title compound, C(9)H(9)N(3)O(3)S, the benzene ring and the N-carbamothio
      ylacetamide unit are oriented at a dihedral angle of 54.82 (4) degrees . The
      dihedral angle between the ring and its attached nitro group is 28.54 (12)
      degrees . An intra-molecular, bifurcated N-H?(O,O) hydrogen bond generates two
      S(6) rings. In the crystal, inversion dimers linked by pairs of N-H?S hydrogen
      bonds generate R(2) (2)(8) loops. Weak C-H?O inter-actions link the dimers.

PMID- 22590436
TI  - Bis(cyclo-hexyl-ammonium) terephthalate.
AB  - In the title mol-ecular salt, 2C(6)H(11)NH(3) (+).C(8)H(4)O(4) (2-), the
      terephthalate dianion is close to being planar (r.m.s. deviation = 0.049 A). In
      the crystal, the cations and anions are linked by N-H?O hydrogen bonds into (010)
      sheets. Of the four terephthalate O atoms, two accept two hydrogen bonds each and
      two accept one hydrogen bond each.

PMID- 22590437
TI  - 6-Fluoro-1H-indole-3-carb-oxy-lic acid.
AB  - In the title compound, C(9)H(6)FNO(2), all the non-H atoms are approximately
      coplanar, the carb-oxy O atoms deviating by 0.0809 and -0.1279 A from the indole
      plane. In the crystal, O-H?O hydrogen bonds link the mol-ecules into dimers which
      are linked via N-H?O hydrogen bonds and pi-pi inter-actions [centroid-centroid
      distance = 3.680 (2) A].

PMID- 22590438
TI  - [(3aS,5aR,8aR,8bS)-2,2,7,7-Tetra-methyl-tetra-hydro-3aH-bis-[1,3]dioxolo[4,5
      b:4',5'-d]pyran-3a-yl]methyl (R)-N-(1-phenyl-eth-yl)sulfamate.
AB  - In the title compound, C(20)H(29)NO(8)S, the two five-membered rings adopt
      envelope conformations (with an O atom at the flap in each case), while the six
      membered pyran ring displays a twist-boat conformation. In the crystal, mol
      ecules are linked by N-H?O hydrogen bonds into a supra-molecular chain running
      along the a axis.

PMID- 22590439
TI  - Precancerous Lesions of the Breast.

PMID- 22590440
TI  - B3 Lesions: Radiological Assessment and Multi-Disciplinary Aspects.
AB  - B3 lesions comprise different histopathological entities that are considered
      benign but 'of unknown biological potential'. These entities may act as risk
      indicators (for both breasts) or as non-obligatory precursors of malignancy.
      Being diagnosed at percutaneous breast biopsy, an additional risk of
      underestimate exists. Imaging appearances, histopathological appearance and risk
      of associated malignancy are presented. B3 lesions of high risk, which thus
      should usually be excised, include atypical ductal hyperplasia (ADH), pleomorphic
      or necrotic type of lobular neoplasia (LIN 3), and papillary lesions with
      atypias. Intermediate risk may be associated with classic lobular carcinoma in
      situ (LIN 2) or flat epithelial atypia (FEA), and low risk with radial sclerosing
      lesions (RSLs) and papillary lesions without atypias. LIN 1 is mostly an
      incidental finding acting as risk indicator. Follow-up is adequate if the initial
      diagnostic problem is solved. According to international guidelines, risk and
      subsequent recommendations should be discussed for each individual patient,
      taking into account biological risk, representative sampling, lesion size, lesion
      extent, percentage of lesion removal, other individual risks, and the possibility
      of surveillance. With vacuum-assisted breast biopsy (VABB), surgery may be
      avoided for more of the small lesions at low risk. Further data collection and
      diligent evaluation may help to better assess the individual risk, to better
      adapt treatment recommendations and avoid overtreatment.

PMID- 22590441
TI  - Early Breast Cancer Precursor Lesions: Lessons Learned from Molecular and
      Clinical Studies.
AB  - Atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), and lobular
      neoplasia (LN) form a group of early precursor lesions that are part of the low
      grade pathway in breast cancer development. This concept implies that the
      neoplastic disease process begins at a stage much earlier than in situ carcinoma.
      We have performed a review of the published literature for the upgrade risk to
      ductal carcinoma in situ or invasive carcinoma in open biopsy after a diagnosis
      of ADH, FEA, or LN in core needle biopsy. This has revealed the highest upgrade
      risk for ADH (28.2% after open biopsy), followed by LN (14.9%), and FEA (10.2%).
      With LN, the pleomorphic subtype is believed to confer a higher risk than
      classical LN. With all types of precursor lesions, careful attention must be paid
      to the clinicopathological correlation for the guidance of the clinical
      management. Follow-up biopsies are generally indicated in ADH, and if there is
      any radiological-pathological discrepancy, also in LN or FEA.

PMID- 22590442
TI  - Ductal Carcinoma in Situ: Clinical Perspective.
AB  - Ductal carcinoma is situ (DCIS) is the fastest growing subtype of breast cancer,
      mainly because of improved screening activities. In contrast to invasive disease,
      DCIS is a local process with excellent survival rates. Current treatment
      strategies include surgery, radiotherapy (RT) and anti-hormonal treatment. The
      selection of an individual risk-adapted therapeutic approach remains
      controversial. This relates especially to the extent of surgery and the
      therapeutic index of adjuvant RT and tamoxifen. Several new trials have been
      published or updated recently that address important clinical issues. There is an
      urgent need to get more insight into the biological behaviour of different
      subtypes of DCIS, and develop more targeted and individualized treatment
      strategies. So far, surgery appears to be the most effective treatment modality.
      A morphology-based treatment model that allows complete resection of certain DCIS
      lesions without further adjuvant measures has not been evaluated prospectively
      and deserves further evaluation.

PMID- 22590443
TI  - Progression of Ductal Carcinoma in Situ from the Pathological Perspective.
AB  - Ductal carcinoma in situ (DCIS) now represents up to 20% of breast cancer cases,
      yet its behaviour is still poorly understood. Morphological classifications go
      some way to predicting prognosis, but more sophisticated approaches are required
      to better tailor therapy to the individual. A number of biological molecules have
      been identified that appear to relate to prognosis and, in model systems, promote
      progression to invasive disease. Some of these, such as COX-2, provide real
      therapeutic opportunities, whilst other marker combinations are showing promise
      in categorising women according to risk. Gene expression studies have led to an
      emerging molecular classification of invasive breast cancer, and it is now
      evident that at least some of these molecular subtypes can be identified at the
      pre-invasive stage. The difference in frequency of these subtypes between DCIS
      and invasive cancer may hold clues as to the biological mechanisms underpinning
      disease transition. It is increasingly clear that the host microenvironment can
      have a major impact on disease behaviour, and as well as acting as potential
      predictive factors, the altered microenvironment phenotype also offers novel
      therapeutic opportunities.

PMID- 22590444
TI  - Myoepithelial Carcinoma: A Rare Neoplasm of the Breast.
AB  - BACKGROUND: Malignant myoepitheliomas of the breast are extremely rare. There has
      been a limited number of published reports of myoepithelial carcinomas
      originating from the breast.  CASE REPORT: We describe a malignant myoepithelioma
      of the breast in a 56-year-old woman. Histological examination showed polygonal
      epithelioid cells and spindle cells with moderate to marked nuclear atypia.
      Immunohistochemistry showed reactivity in the spindle cells for smooth muscle
      actin, cytokeratin (AE1/AE3), and p63, indicating a myoepithelial cell lineage of
      tumor cells. The patient underwent radical surgical excision of the lesion and
      axillary lymph node dissection. She demonstrated no evidence of recurrence over
      an 11-month follow-up.  CONCLUSIONS: We suggest myoepithelial carcinomas of the
      breast be managed with appropriate surgical clearance. A multidisciplinary
      approach is usually required.

PMID- 22590445
TI  - Cystic Lymphangioma of the Breast: Magnetic Resonance Imaging Features.
AB  - BACKGROUND: The aim of this study was to report magnetic resonance imaging (MRI)
      features of cystic lymphangiomas of the breast.  METHODS: MRI of the breast was
      performed using a phased-array double breast coil with a 1.5-T MR scanner.
      Routine T1 and T2 and post-contrast sequential imaging was performed.  RESULTS:
      The MRI characteristics of cystic lymphangioma in the breast are described. 
      CONCLUSION: MR imaging provides for multiplanar evaluation and diagnosis of
      cystic lymphangioma of the breast, which is a rare occurrence.

PMID- 22590446
TI  - Nipple-Sparing Mastectomy - Extended Indications and Limitations.
AB  - If mastectomy is indicated for removal of breast cancer, the nipple areola
      complex (NAC) is routinely excised during surgery followed by nipple
      reconstruction. Despite advances in reconstruction techniques, removal of the NAC
      often results in a sense of mutilation. However, recent studies regarding the
      tumorigenic involvement of the NAC have provided some evidence that in carefully
      selected patients the NAC could be preserved. Nipplesparing mastectomy (NSM)
      preserves the breast skin envelope and the NAC, and has therefore emerged as an
      alternative to conventional radical mastectomies. BecauseNSM leaves no or sparse
      retroareolar ductal tissue, NSM is increasingly considered as oncologically safe
      both in patients with small and peripherally located tumors and in women with
      high breast cancer risk, who opt for prophylactic mastectomy. Moreover, NSM has
      been applied in patients with large and centrally located or multicentric
      invasive carcinomas but oncologic safety as well as postoperative complications
      such as NAC necrosis are still controversial. Since long-term data are limited,
      there is no general recommendation for NSM indications. To evaluate if
      indications for NSM may be rather enlarged under certain conditions, we performed
      a MEDLINE search for studies published between 2003 and 2009.

PMID- 22590447
TI  - Update 2010 of the German AGO Recommendations for the Diagnosis and Treatment of
      Early and Metastatic Breast Cancer - Chapter A: Surgery, Pathology and Prognostic
      Factors, Adjuvant and Neoadjuvant Therapy, Adjuvant Radiotherapy.

PMID- 22590448
TI  - New Developments in Breast Cancer Therapy Presented at ASCO 2010.

PMID- 22590450
TI  - Central Europeon Cooperative Oncology Group.

PMID- 22590449
TI  - Are Three Weeks of Whole-Breast Radiotherapy as Good as Five Weeks in Early
      Breast Cancer? - 10 Year Follow-Up in the Canadian Trial of Hypofractionated
      Radiation Therapy.
AB  - Whole breast irradiation (WBI) is considered standard of care among both patients
      having undergone breast-conserving therapy for invasive breast carcinoma and
      selected cases post mastectomy. Since the introduction of WBI, clinical trials
      have been conducted to define the optimal dose, schedule and length of WBI aiming
      to increase efficacy while reducing toxicity. In the paper discussed in this
      issue's journal club, Whelan et al. present the latest in a series of randomized
      clinical trials on hypofractionated radiotherapy.

PMID- 22590451
TI  - Profiling of REST-Dependent microRNAs Reveals Dynamic Modes of Expression.
AB  - Multipotent neural stem cells (NSCs) possess the ability to self-renew and
      differentiate into both neurons and glia. However, the detailed mechanisms
      underlying NSC fate decisions are not well understood. Recent work suggests that
      the interaction between cell type specific transcription factors and microRNAs
      (miRNAs) is important as resident neural stem/progenitor cells give rise to
      functionally mature neurons. Recently, we demonstrated that the transcriptional
      repressor REST (RE1-silencing transcription factor) is essential to prevent
      precocious neuronal differentiation and maintain NSC self-renewal in the adult
      hippocampus. Here we show that REST is required for orchestrating the expression
      of distinct subsets of miRNAs in primary mouse NSC cultures, a physiologically
      relevant cell type. Using miRNA array profiling, we identified known REST
      regulated miRNA genes, as well as previously uncharacterized REST-dependent
      miRNAs. Interestingly, in response to proliferation and differentiation stimuli,
      REST-regulated miRNAs formed distinct clusters and displayed variable expression
      dynamics. These results suggest that REST functions in a context-dependent manner
      through its target miRNAs for mediating neuronal production.

PMID- 22590452
TI  - Strategic insight and age-related goal-neglect influence risky decision-making.
AB  - Maximizing long-run gains often requires taking on some degree of risk, yet
      decision-makers often exhibit risk aversion (RA), rejecting risky prospects even
      when these have higher expected value (EV) than safer alternatives. We
      investigated whether explicit strategy instruction and practice can decrease
      prepotent RA, and whether aging impacts the efficacy of such an intervention.
      Participants performed a paired lottery task with options varying in risk and
      magnitude, both before and after practice with a similar task that encouraged
      maximization of EV and instruction to use this strategy in risky decisions. In
      both younger and older adults (OAs), strategy training reduced RA. Although RA
      was age-equivalent at baseline, larger training effects were observed in younger
      adults (YAs). These effects were not explained by risk-related (i.e., affective)
      interference effects or computation ability, but were consistent with a
      progressive, age-related neglect of the strategy across trials. Our findings
      suggest that strategy training can diminish RA, but that training efficacy is
      reduced among OAs, potentially due to goal neglect. We discuss implications for
      neural mechanisms that may distinguish older and YAs' risky decision-making.

PMID- 22590453
TI  - Differential changes of metabolic brain activity and interregional functional
      coupling in prefronto-limbic pathways during different stress conditions:
      functional imaging in freely behaving rodent pups.
AB  - The trumpet-tailed rat or degu (Octodon degus) is an established model to
      investigate the consequences of early stress on the development of emotional
      brain circuits and behavior. The aim of this study was to identify brain
      circuits, that respond to different stress conditions and to test if acute stress
      alters functional coupling of brain activity among prefrontal and limbic regions.
      Using functional imaging (2-Fluoro-deoxyglucose method) in 8-day-old male degu
      pups the following stress conditions were compared: (A) pups together with
      parents and siblings (control), (B) separation of the litter from the parents,
      (C) individual separation from parents and siblings, and (D) individual
      separation and presentation of maternal calls. Condition (B) significantly
      downregulated brain activity in the prefrontal cortex, hippocampus, nucleus
      accumbens (NAcc), and sensory areas compared to controls. Activity decrease was
      even more pronounced during condition (C), where, in contrast to all other
      regions, activity in the PAG was increased. Interestingly, brain activity in
      stress-associated brain regions such as the amygdala and habenula was not
      affected. In condition (D) maternal vocalizations "reactivated" brain activity in
      the cingulate and precentral medial cortex, NAcc, and striatum and in sensory
      areas. In contrast, reduced activity was measured in the prelimbic and
      infralimbic cortex (IL) and in the hippocampus and amygdala. Correlation analysis
      revealed complex, region- and situation-specific changes of interregional
      functional coupling among prefrontal and limbic brain regions during stress
      exposure. We show here for the first time that early life stress results in a
      widespread reduction of brain activity in the infant brain and changes
      interregional functional coupling. Moreover, maternal vocalizations can partly
      buffer stress-induced decrease in brain activity in some regions and evoked very
      different functional coupling patterns compared to the three other conditions.

PMID- 22590454
TI  - Time-dependent dual effects of high levels of unconjugated bilirubin on the human
      blood-brain barrier lining.
AB  - In neonatal jaundice, high levels of unconjugated bilirubin (UCB) may induce
      neurological dysfunction (BIND). Recently, it was observed that UCB induces
      alterations on brain microvasculature, which may facilitate its entrance into the
      brain, but little is known about the steps involved. To evaluate if UCB damages
      the integrity of human brain microvascular endothelial cells (HBMECs), we used 50
      or 100 MUM UCB plus human serum albumin, to mimic the neuropathological
      conditions where levels of UCB free species correspond to moderate and severe
      neonatal jaundice, respectively. Our results point to a biphasic response of
      HBMEC to UCB depending on time of exposure. The early response includes increased
      number of caveolae and caveolin-1 expression, as well as upregulation of vascular
      endothelial growth factor (VEGF) and its receptor 2 (VEGFR-2) with no alterations
      of the paracellular permeability. In contrast, effects by sustained
      hyperbilirubinemia are the reduction in zonula occludens (ZO)-1 and beta-catenin
      levels and thus of tight junctions (TJ) strands and cell-to-cell contacts. In
      addition, reduction of the transendothelial electrical resistance (TEER) and
      increased paracellular permeability are observed, revealing loss of the barrier
      properties. The 72 h of HBMEC exposure to UCB triggers a cell response to the
      stressful stimulus evidenced by increased autophagy. In this later condition, the
      UCB intracellular content and the detachment of both viable and non-viable cells
      are increased. These findings contribute to understand why the duration of
      hyperbilirubinemia is considered one of the risk factors of BIND. Indeed,
      facilitated brain entrance of the free UCB species will favor its parenchymal
      accumulation and neurological dysfunction.

PMID- 22590455
TI  - Are there three subdivisions in the primate subthalamic nucleus?
AB  - The prevailing academic opinion holds that the subthalamic nucleus (STN) consists
      of three parts, each anatomically distinct and selectively associated with
      cognitive, emotional, or motor functioning. We independently tested this
      assumption by summarizing the results from 33 studies on STN subdivisions in
      human and nonhuman primates. The studies were conducted from 1925 to 2010 and
      feature three different techniques: electrical lesions, anterograde and
      retrograde tracers, and classical cytoarchitectonics. Our results reveal scant
      evidence in support of a tripartite STN. Instead, our results show that the
      variability across studies is surprisingly large, both in the number of
      subdivisions and in their anatomical localization. We conclude that the number of
      subdivisions in the STN remains uncertain, and that academic consensus in support
      of a tripartite STN is presently unwarranted.

PMID- 22590456
TI  - Taste quality and intensity of 100 stimuli as reported by rats: the taste
      location association task.
AB  - The interpretation of neural activity related to sensory stimulation requires an
      understanding of the subject's perception of the stimulation. Previous methods
      used to evaluate the perception of chemosensory stimuli by rodents have distinct
      limitations. We developed a novel behavioral paradigm, the taste-location
      association task, to complement these methods. First we tested if rats are able
      to learn associations between five basic taste stimuli and their spatial
      locations. This spatial task was based on four prototypical tastants and water.
      All four rats trained to perform the task reached levels of performance well
      above chance. Control trials demonstrated that the rats used only taste cues.
      Further, the learned stimulus set was resistant to interference, allowing for
      generalization experiments performed subsequently. We tested the rats' gustatory
      generalizations of 100 tastants to the five trained stimuli, both regarding their
      taste qualities as well as intensity ratings. The taste profiles generated by
      these experiments contribute to the understanding of how perception of the
      specific taste stimuli relate to the perception of the five basic taste qualities
      in intact behaving rats. In this large taste space we found that intensity plays
      a major role. Furthermore, umami stimuli were not reported as being similar to
      other basic tastants. Our new paradigm enables neurophysiological studies of
      taste-based learning and memory in awake, freely moving animals.

PMID- 22590457
TI  - Sudden death of cardiac origin and psychotropic drugs.
AB  - Mortality rate is high in psychiatric patients versus general population. An
      important cause of this increased mortality is sudden cardiac death (SCD) as a
      major side-effect of psychotropic drugs. These SCDs generally result from
      arrhythmias occurring when the posology is high and may attain a toxic threshold
      but also at dosages within therapeutic range, in the presence of risk factors.
      There are three kinds of risk factors: physiological (e.g., low cardiac rate of
      sportsmen), physiopathological (e.g., hepatic insufficiency, hypothyroidism) and
      "therapeutic" (due to interactions between psychotropic drugs and other
      medicines). Association of pharmacological agents may increase the likelihood of
      SCDs either by (i) a pharmacokinetic mechanism (e.g., increased torsadogenic
      potential of a psychotropic drug when its destruction and/or elimination are
      compromised) or (ii) a pharmacodynamical mechanism (e.g., mutual potentiation of
      proarrhythmic properties of two drugs). In addition, some psychotropic drugs may
      induce sudden death in cases of pre-existing congenital cardiopathies such as (i)
      congenital long QT syndrome, predisposing to torsade de pointes that eventually
      cause syncope and sudden death. (ii) A Brugada syndrome, that may directly cause
      ventricular fibrillation due to reduced sodium current through Nav1.5 channels.
      Moreover, psychotropic drugs may be a direct cause of cardiac lesions also
      leading to SCD. This is the case, for example, of phenothiazines responsible for
      ischemic coronaropathies and of clozapine that is involved in the occurrence of
      myocarditis. The aims of this work are to delineate: (i) the risk of SCD related
      to the use of psychotropic drugs; (ii) mechanisms involved in the occurrence of
      such SCD; (iii) preventive actions of psychotropic drugs side effects, on the
      basis of the knowledge of patient-specific risk factors, documented from clinical
      history, ionic balance, and ECG investigation by the psychiatrist.

PMID- 22590458
TI  - Estimated Tissue and Blood N(2) Levels and Risk of Decompression Sickness in Deep
      , Intermediate-, and Shallow-Diving Toothed Whales during Exposure to Naval
      Sonar.
AB  - Naval sonar has been accused of causing whale stranding by a mechanism which
      increases formation of tissue N(2) gas bubbles. Increased tissue and blood N(2)
      levels, and thereby increased risk of decompression sickness (DCS), is thought to
      result from changes in behavior or physiological responses during diving.
      Previous theoretical studies have used hypothetical sonar-induced changes in both
      behavior and physiology to model blood and tissue N(2) tension [Formula: see
      text], but this is the first attempt to estimate the changes during actual
      behavioral responses to sonar. We used an existing mathematical model to estimate
      blood and tissue N(2) tension [Formula: see text] from dive data recorded from
      sperm, killer, long-finned pilot, Blainville's beaked, and Cuvier's beaked whales
      before and during exposure to Low- (1-2 kHz) and Mid- (2-7 kHz) frequency active
      sonar. Our objectives were: (1) to determine if differences in dive behavior
      affects risk of bubble formation, and if (2) behavioral- or (3) physiological
      responses to sonar are plausible risk factors. Our results suggest that all
      species have natural high N(2) levels, with deep diving generally resulting in
      higher end-dive [Formula: see text] as compared with shallow diving. Sonar
      exposure caused some changes in dive behavior in both killer whales, pilot whales
      and beaked whales, but this did not lead to any increased risk of DCS. However,
      in three of eight exposure session with sperm whales, the animal changed to
      shallower diving, and in all these cases this seem to result in an increased risk
      of DCS, although risk was still within the normal risk range of this species.
      When a hypothetical removal of the normal dive response (bradycardia and
      peripheral vasoconstriction), was added to the behavioral response during model
      simulations, this led to an increased variance in the estimated end-dive N(2)
      levels, but no consistent change of risk. In conclusion, we cannot rule out the
      possibility that a combination of behavioral and physiological responses to sonar
      have the potential to alter the blood and tissue end-dive N(2) tension to levels
      which could cause DCS and formation of in vivo bubbles, but the actually observed
      behavioral responses of cetaceans to sonar in our study, do not imply any
      significantly increased risk of DCS.

PMID- 22590459
TI  - Heart rate variability predicts cell death and inflammatory responses to global
      cerebral ischemia.
AB  - This study examines the relationship between autonomic functioning and
      neuropathology following cardiac arrest (CA) in mice. Within 24 h of CA,
      parasympathetic cardiac control, as indexed by high frequency (HF) heart rate
      variability, rapidly decreases. By day 7 after CA, HF heart rate variability was
      inversely correlated with neuronal damage and microglial activation in the
      hippocampus. Thus, by virtue of its sensitivity to central insult, HF heart rate
      variability may offer an inexpensive, non-invasive method of monitoring
      neuropathological processes following CA. The inverse linear relationships
      between heart rate variability and brain damage after CA also may partially
      explain why low heart rate variability is associated with increased morbidity and
      mortality in myocardial infarction patients.

PMID- 22590460
TI  - Effects of Renal Sympathetic Denervation on 24-hour Blood Pressure Variability.
AB  - BACKGROUND: In patients with arterial hypertension, increased blood pressure (BP)
      variability contributes to end organ damage independently from mean levels of
      arterial BP. Increased BP variability has been linked to alterations in autonomic
      function including sympathetic overdrive. We hypothesized that catheter-based
      renal sympathetic denervation (RDN) confers beneficial effects on BP variability.
      METHODS AND RESULTS: Eleven consecutive patients with therapy-refractory arterial
      hypertension (age 68.9 +/- 7.0 years; baseline systolic BP 189 +/- 23 mmHg
      despite medication with 5.6 +/- 2.1 antihypertensive drugs) underwent bilateral
      RDN. Twenty-four hour ambulatory BP monitoring (ABPM) was performed before RDN
      and 6 months thereafter. BP variability was primarily assessed by means of
      standard deviation of 24-h systolic arterial BP (SD(sys)). Secondary measures of
      BP variability were maximum systolic BP (MAX(sys)) and maximum difference between
      two consecutive readings of systolic BP (Deltamax(sys)) over 24 h. Six months
      after RDN, SD(sys), MAX(sys), and Deltamax(sys) were significantly reduced from
      16.9 +/- 4.6 to 13.5 +/- 2.5 mmHg (p = 0.003), from 190 +/- 22 to 172 +/- 20 mmHg
      (p < 0.001), and from 40 +/- 15 to 28 +/- 7 mmHg (p = 0.006), respectively,
      without changes in concomitant antihypertensive therapy. Reductions of SD(sys),
      MAX(sys), and Deltamax(sys) were observed in 10/11 (90.9%), 11/11 (100%), and
      9/11 (81.8%) patients, respectively. Although we noted a significant reduction of
      systolic office BP by 30.4 +/- 27.7 mmHg (p = 0.007), there was only a trend in
      reduction of average systolic BP assessed from ABPM (149 +/- 19 to 142 +/- 18
      mmHg; p = 0.086). CONCLUSION: In patients with therapy-refractory arterial
      hypertension, RDN leads to significant reductions of BP variability. Effects of
      RDN on BP variability over 24 h were more pronounced than on average levels of
      BP.

PMID- 22590461
TI  - Transcranial Direct Current Stimulation of the Frontal Eye Fields during Pro- and
      Antisaccade Tasks.
AB  - Transcranial direct current stimulation (tDCS) has been successfully applied to
      cortical areas such as the motor cortex and visual cortex. In the present study,
      we examined whether tDCS can reach and selectively modulate the excitability of
      the frontal eye field (FEF). In order to assess potential effects of tDCS, we
      measured saccade latency, landing point, and its variability in a simple
      prosaccade task and in an antisaccade task. In the prosaccade task, we found that
      anodal tDCS shortened the latency of saccades to a contralateral visual cue.
      However, cathodal tDCS did not show a significant modulation of saccade latency.
      In the antisaccade task, on the other hand, we found that the latency for
      ipisilateral antisaccades was prolonged during the stimulation, whereas anodal
      stimulation did not modulate the latency of antisaccades. In addition, anodal
      tDCS reduced the erroneous saccades toward the contralateral visual cue. These
      results in the antisaccade task suggest that tDCS modulates the function of FEF
      to suppress reflexive saccades to the contralateral visual cue. Both in the
      prosaccade and antisaccade tasks, we did not find any effect of tDCS on saccade
      landing point or its variability. Our present study is the first to show effects
      of tDCS over FEF and opens the possibility of applying tDCS for studying the
      functions of FEF in oculomotor and attentional performance.

PMID- 22590462
TI  - Storage costs and heuristics interact to produce patterns of aphasic sentence
      comprehension performance.
AB  - BACKGROUND: Despite general agreement that aphasic individuals exhibit difficulty
      understanding complex sentences, the nature of sentence complexity itself is
      unresolved. In addition, aphasic individuals appear to make use of heuristic
      strategies for understanding sentences. This research is a comparison of
      predictions derived from two approaches to the quantification of sentence
      complexity, one based on the hierarchical structure of sentences, and the other
      based on dependency locality theory (DLT). Complexity metrics derived from these
      theories are evaluated under various assumptions of heuristic use. METHOD: A set
      of complexity metrics was derived from each general theory of sentence complexity
      and paired with assumptions of heuristic use. Probability spaces were generated
      that summarized the possible patterns of performance across 16 different sentence
      structures. The maximum likelihood of comprehension scores of 42 aphasic
      individuals was then computed for each probability space and the expected scores
      from the best-fitting points in the space were recorded for comparison to the
      actual scores. Predictions were then compared using measures of fit quality
      derived from linear mixed effects models. RESULTS: All three of the metrics that
      provide the most consistently accurate predictions of patient scores rely on
      storage costs based on the DLT. Patients appear to employ an Agent-Theme
      heuristic, but vary in their tendency to accept heuristically generated
      interpretations. Furthermore, the ability to apply the heuristic may be degraded
      in proportion to aphasia severity. CONCLUSION: DLT-derived storage costs provide
      the best prediction of sentence comprehension patterns in aphasia. Because these
      costs are estimated by counting incomplete syntactic dependencies at each point
      in a sentence, this finding suggests that aphasia is associated with reduced
      availability of cognitive resources for maintaining these dependencies.

PMID- 22590463
TI  - Influence of threat and serotonin transporter genotype on interference effects.
AB  - Emotion-cognition interactions are critical in goal-directed behavior and may be
      disrupted in psychopathology. Growing evidence also suggests that emotion
      cognition interactions are modulated by genetic variation, including genetic
      variation in the serotonin system. The goal of the current study was to examine
      the impact of threat-related distracters and serotonin transporter promoter
      polymorphism (5-HTTLPR/rs25531) on cognitive task performance in healthy females.
      Using a novel threat-distracter version of the Multi-Source Interference Task
      specifically designed to probe emotion-cognition interactions, we demonstrate a
      robust and temporally dynamic modulation of cognitive interference effects by
      threat-related distracters relative to other distracter types and relative to no
      distracter condition. We further show that threat-related distracters have
      dissociable and opposite effects on cognitive task performance in easy and
      difficult task conditions, operationalized as the level of response interference
      that has to be surmounted to produce a correct response. Finally, we present
      evidence that the 5-HTTLPR/rs25531 genotype in females modulates susceptibility
      to cognitive interference in a global fashion, across all distracter conditions,
      and irrespective of the emotional salience of distracters, rather than
      specifically in the presence of threat-related distracters. Taken together, these
      results add to our understanding of the processes through which threat-related
      distracters affect cognitive processing, and have implications for our
      understanding of disorders in which threat signals have a detrimental effect on
      cognition, including depression and anxiety disorders.

PMID- 22590464
TI  - Syllable effects in a fragment-detection task in italian listeners.
AB  - In the line of the monitoring studies initiated by Mehler et al. (1981), a group
      of Italian listeners were asked to detect auditory CV and CVC targets in carrier
      words beginning with a CV, a CVC, or a CVG (G = geminate) syllable with variable
      initial syllable stress. By slowing participants reaction times (RTs), using both
      catch and foil trials, a syllable effect was found, partially modulated by
      participants' speed and stress location. When catch trials were removed in a
      second experiment the syllable effect was not observed, even if RTs were similar
      to that of the first experiment. We discuss these data in relation to the
      language transparency hypothesis, the nature of the pivotal consonant, and the
      resonance-based ART model for speech perception (Grossberg, 2003).

PMID- 22590465
TI  - Trace elements affect methanogenic activity and diversity in enrichments from
      subsurface coal bed produced water.
AB  - Microbial methane from coal beds accounts for a significant and growing
      percentage of natural gas worldwide. Our knowledge of physical and geochemical
      factors regulating methanogenesis is still in its infancy. We hypothesized that
      in these closed systems, trace elements (as micronutrients) are a limiting factor
      for methanogenic growth and activity. Trace elements are essential components of
      enzymes or cofactors of metabolic pathways associated with methanogenesis. This
      study examined the effects of eight trace elements (iron, nickel, cobalt,
      molybdenum, zinc, manganese, boron, and copper) on methane production, on mcrA
      transcript levels, and on methanogenic community structure in enrichment cultures
      obtained from coal bed methane (CBM) well produced water samples from the Powder
      River Basin, Wyoming. Methane production was shown to be limited both by a lack
      of additional trace elements as well as by the addition of an overly concentrated
      trace element mixture. Addition of trace elements at concentrations optimized for
      standard media enhanced methane production by 37%. After 7 days of incubation,
      the levels of mcrA transcripts in enrichment cultures with trace element
      amendment were much higher than in cultures without amendment. Transcript levels
      of mcrA correlated positively with elevated rates of methane production in
      supplemented enrichments (R(2) = 0.95). Metabolically active methanogens,
      identified by clone sequences of mcrA mRNA retrieved from enrichment cultures,
      were closely related to Methanobacterium subterraneum and Methanobacterium
      formicicum. Enrichment cultures were dominated by M. subterraneum and had
      slightly higher predicted methanogenic richness, but less diversity than
      enrichment cultures without amendments. These results suggest that varying
      concentrations of trace elements in produced water from different subsurface coal
      wells may cause changing levels of CBM production and alter the composition of
      the active methanogenic community.

PMID- 22590466
TI  - Host defense pathways against fungi: the basis for vaccines and immunotherapy.
AB  - Fungal vaccines have long been a goal in the fields of immunology and
      microbiology to counter the high mortality and morbidity rates owing to fungal
      diseases, particularly in immunocompromised patients. However, the design of
      effective vaccination formulations for durable protection to the different fungi
      has lagged behind due to the important differences among fungi and their biology
      and our limited understanding of the complex host-pathogen interactions and
      immune responses. Overcoming these challenges is expected to contribute to
      improved vaccination strategies aimed at personalized efficacy across distinct
      target patient populations. This likely requires the integration of multifaceted
      approaches encompassing advanced immunology, systems biology, immunogenetics, and
      bioinformatics in the fields of fungal and host biology and their reciprocal
      interactions.

PMID- 22590467
TI  - Understanding the role of host hemocytes in a squid/vibrio symbiosis using
      transcriptomics and proteomics.
AB  - The symbiosis between the squid, Euprymna scolopes, and the bacterium, Vibrio
      fischeri, serves as a model for understanding interactions between beneficial
      bacteria and animal hosts. The establishment and maintenance of the association
      is highly specific and depends on the selection of V. fischeri and exclusion of
      non-symbiotic bacteria from the environment. Current evidence suggests that the
      host's cellular innate immune system, in the form of macrophage-like hemocytes,
      helps to mediate host tolerance of V. fischeri. To begin to understand the role
      of hemocytes in this association, we analyzed these cells by high-throughput 454
      transcriptomic and liquid chromatography/tandem mass spectrometry (LC-MS/MS)
      proteomic analyses. 454 high-throughput sequencing produced 650, 686 reads
      totaling 279.9 Mb while LC-MS/MS analyses of circulating hemocytes putatively
      identified 702 unique proteins. Several receptors involved with the recognition
      of microbial-associated molecular patterns were identified. Among these was a
      complete open reading frame to a putative peptidoglycan recognition protein
      (EsPGRP5) with conserved residues for amidase activity. Assembly of the hemocyte
      transcriptome showed EsPGRP5 had high coverage, suggesting it is among the 5%
      most abundant transcripts in circulating hemocytes. Other transcripts and
      proteins identified included members of the conserved NF-kappaB signaling
      pathway, putative members of the complement pathway, the carbohydrate binding
      protein galectin, and cephalotoxin. Quantitative Real-Time PCR of complement-like
      genes, cephalotoxin, EsPGRP5, and a nitric oxide synthase showed differential
      expression in circulating hemocytes from adult squid with colonized light organs
      compared to those isolated from hosts where the symbionts were removed. These
      data suggest that the presence of the symbiont influences gene expression of the
      cellular innate immune system of E. scolopes.

PMID- 22590468
TI  - Conditional IL-2 Gene Deletion: Consequences for T Cell Proliferation.
AB  - To explore the role of interleukin-2 (IL-2) in T cell proliferation, and to
      circumvent the IL-2 deficiency autoimmune syndrome of conventional il2 gene
      deletion, mice were created to allow conditional il2 gene deletion when treated
      with the estrogen analog, tamoxifen (TAM) as adults. Splenocytes from four
      different mouse strains, C57Bl/6 wild type (WT), conventional IL-2(-/-), TAM
      treated Cre recombinase-negative (Cre-)/IL2fl/fl, and Cre recombinase-positive
      (Cre+)/IL2fl/fl, were activated with anti-CD3 and anti-CD28, and monitored for
      CD4+ and CD8+ T cell lymphocyte blastogenesis, aerobic glycolysis, BrdU
      incorporation into newly synthesized DNA, and CFSE dye dilution to monitor cell
      division. IL-2 production was monitored by quantitative ELISA and multiple
      additional cytokines were monitored by quantitative protein-bead arrays.
      Splenocytes from conventional IL-2(-/-) and TAM-treated Cre+ mice resulted in
      undetectable IL-2 production by ELISA, so that both strains were IL-2-deficient.
      As monitored by flow cytometry, activated CD4+ and CD8+ T cells from WT, Cre+,
      and Cre- mice all underwent blastogenesis, whereas far fewer cells from
      conventional IL-2(-/-) mice did so. By comparison, only cells from IL-2
      sufficient WT and Cre- mice switched to aerobic glycolysis as evidenced by a drop
      in media pH. Blastogenesis was mirrored by BrdU incorporation and CFSE dye
      dilution by CD4+ and CD8+ T cells from WT, Cre+, and Cre- mice, which were all
      equivalent, while proliferation of cells from conventional IL-2(-/-) mice was
      compromised. Splenocytes from IL-2 deficient conventional IL-2(-/-) mice produced
      low or undetectable other gamma(c)-chain cytokines (IL-4, IL-7, IL-9, IL-13, IL
      15, and IL-21), whereas production of these gamma(c)-chain cytokines from IL-2
      deficient conditional IL-2(-/-) Cre+ mice were comparable with WT and Cre- mice.
      These results indicate that CD4+ and CD8+ T cell blastogenesis cannot be
      attributable to IL-2 alone, but a switch to aerobic glycolysis was attributable
      to IL-2, and proliferation after CD3/CD28 activation is dependent on gamma(c)
      chain cytokines, and not CD3/28 triggering per se.

PMID- 22590470
TI  - The Tricky Balancing Act of using Heat Shock Proteins for Cross-Presentation.

PMID- 22590469
TI  - Comparative Genomics Reveals Key Gain-of-Function Events in Foxp3 during
      Regulatory T Cell Evolution.
AB  - The immune system has the ability to suppress undesirable responses, such as
      those against commensal bacteria, food, and paternal antigens in placenta
      pregnancy. The lineage-specific transcription factor Foxp3 orchestrates the
      development and function of regulatory T cells underlying this immunological
      tolerance. Despite the crucial role of Foxp3 in supporting immune homeostasis,
      little is known about its origin, evolution, and species conservation. We explore
      these questions using comparative genomics, structural modeling, and functional
      analyses. Our data reveal that key gain-of-function events occurred during the
      evolution of Foxp3 in higher vertebrates. We identify key conserved residues in
      its forkhead domain and show a detailed analysis of the N-terminal region of
      Foxp3, which is only conserved in mammals. These components are under purifying
      selection, and our mutational analyses demonstrate that they are essential for
      Foxp3 function. Our study points to critical functional adaptations in immune
      tolerance among higher vertebrates, and suggests that Foxp3-mediated
      transcriptional mechanisms emerged during mammalian evolution as a stepwise gain
      of functional domains that enabled Foxp3 to interact with a multitude of
      interaction partners.

PMID- 22590471
TI  - White matter hyperintensities and the course of depressive symptoms in elderly
      people with mild dementia.
AB  - OBJECTIVES: To explore the relationship between white matter hyperintensities
      (WMH) and the prevalence and course of depressive symptoms in mild Alzheimer's
      disease (AD) and Lewy body dementia. DESIGN: This is a prospective cohort study
      conducted in secondary care outpatient clinics in western Norway. SUBJECTS: The
      study population consisted of 77 elderly people with mild dementia diagnosed
      according to standardised criteria. METHODS: Structured clinical interviews and
      physical, neurological, psychiatric, and neuropsychological examinations were
      performed and routine blood tests were taken. Depression was assessed using the
      depression subitem of the Neuropsychiatric Inventory and the Montgomery-Asberg
      Depression Rating Scale (MADRS). A standardised protocol for magnetic resonance
      imaging scan was used, and the volumes of WMH were quantified using an automated
      method, followed by manual editing. RESULTS: The volumes of total and frontal
      deep WMH were significantly and positively correlated with baseline severity of
      depressive symptoms, and depressed patients had significantly higher volumes of
      total and frontal deep WMH than non-depressed patients. Higher volumes of WMH
      were also associated with having a high MADRS score and incident and persistent
      depression at follow-up. After adjustment for potential confounders, frontal deep
      WMH, in addition to prior depression and non-AD dementia, were still
      significantly associated with baseline depressive symptoms (p = 0.015, OR 3.703,
      95% CI 1.294-10.593). Similar results emerged for total WMH. CONCLUSION: In
      elderly people with mild dementia, volumes of WMH, in particular frontal deep
      WMH, were positively correlated with baseline severity of depressive symptoms,
      and seemed to be associated with persistent and incident depression at follow-up.
      Further studies of the mechanisms that determine the course of depression in mild
      dementia are needed.

PMID- 22590472
TI  - The role of suboptimal home-measured blood pressure control for cognitive
      decline.
AB  - AIM: We aim to analyze if there is any correlation between suboptimal home-/self
      measured blood pressure values and the results from neuropsychological screening
      tests for early cognitive impairment. METHODS: We studied 325 patients with
      treated hypertension. Mean age was 66.12 (+/-10.1) years. There were 119 (36.6%)
      male and 206 (63.4%) female patients, among them 52 (16%) with atrial
      fibrillation. Neuropsychological tests performed were the Mini-Mental State
      Examination, Montreal Cognitive Assessment, and Hachinski Ischemic Score;
      additionally, home-measured blood pressure was used. RESULTS: There is a
      nonlinear age- and risk factor-dependent correlation between early stages of
      cognitive impairment and suboptimal home-measured blood pressure. CONCLUSION: The
      use of specific and sensitive neuropsychological tests for early cognitive
      impairment in patients with suboptimal home-measured blood pressure is effective
      in the everyday practice.

PMID- 22590473
TI  - Comparison of four verbal memory tests for the diagnosis and predictive value of
      mild cognitive impairment.
AB  - BACKGROUND: Mild cognitive impairment (MCI) is considered to be an early stage of
      a neurodegenerative disorder, particularly Alzheimer's disease, and the clinical
      diagnosis requires the objective demonstration of cognitive deficits. The aim of
      the present study was to evaluate the predictive value of MCI for the conversion
      to dementia when using four different verbal memory tests (Logical Memory, LM;
      California Verbal Learning Test, CVLT; Verbal Paired-Associate Learning, VPAL;
      and Digit Span, DS) in the MCI criteria. METHODS: Participants were consecutive
      patients with subjective cognitive complaints who performed a comprehensive
      neuropsychological evaluation and were not demented, observed in a memory clinic
      setting. RESULTS: At baseline, 272 non-demented patients reporting subjective
      cognitive complaints were included. During the follow-up time (3.0 +/- 1.9
      years), 58 patients converted to dementia and 214 did not. Statistically
      significant differences between the converters and non-converters were present in
      LM, VPAL, and CVLT. A multivariate Cox regression analysis combining the four
      memory tests revealed that only the CVLT test remained significant as a predictor
      of conversion to dementia. Non-demented patients with cognitive complaints
      diagnosed as having MCI according to abnormal (<1.5 SD) learning in the CVLT test
      had a 3.61 higher risk of becoming demented during the follow-up. CONCLUSION: The
      verbal memory assessment using the CVLT should be preferred in the diagnostic
      criteria of MCI for a more accurate prediction of conversion to dementia.

PMID- 22590474
TI  - Exercise and early-onset Alzheimer's disease: theoretical considerations.
AB  - BACKGROUND/AIMS: Although studies show a negative relationship between physical
      activity and the risk for cognitive impairment and late-onset Alzheimer's
      disease, studies concerning early-onset Alzheimer's disease (EOAD) are lacking.
      This review aims to justify the value of exercise interventions in EOAD by
      providing theoretical considerations that include neurobiological processes.
      METHODS: A literature search on key words related to early-onset dementia,
      exercise, imaging, neurobiological mechanisms, and cognitive reserve was
      performed. RESULTS/CONCLUSION: Brain regions and neurobiological processes
      contributing to the positive effects of exercise are affected in EOAD and, thus,
      provide theoretical support for exercise interventions in EOAD. Finally, we
      present the design of a randomized controlled trial currently being conducted in
      early-onset dementia patients.

PMID- 22590475
TI  - Why is it so difficult to evaluate nursing interventions in dementia?
AB  - Two recent health technology assessment (HTA) reports published in Germany
      focused on non-pharmacological interventions for patients with dementia. One of
      the major results was the poor methodological quality of the studies in this
      field. This paper concisely presents the main quantitative and qualitative
      findings of the HTA report published by the German Agency for HTA at the
      Institute of Medical Information and Documentation (dahta@DIMDI), followed by a
      detailed discussion of the major methodological problems observed for the
      inclusion criteria, interventions, the setting, number of patients included,
      duration of observation, comparators, clinical endpoints, health economics, and,
      most obvious, the impossibility of blinding and eliminating placebo effects for
      future clinical studies. We conclude with several suggestions addressing these
      challenges for future research in this field.

PMID- 22590476
TI  - Risk factors for dementia in a senegalese elderly population aged 65 years and
      over.
AB  - BACKGROUND: With the aging of the population, dementia is increasing worldwide.
      The objective of this study was to identify risk factors for dementia in an
      elderly population utilizing a primary health care service in Dakar, Senegal.
      METHODS: Through a cross-sectional study conducted from March 2004 to December
      31, 2005, 507 elderly patients aged >=65 years who came to the Social and Medical
      Center of IPRES, Dakar, Senegal, were first screened with the screening interview
      questionnaire 'Aging in Senegal'. Those who were cognitively impaired underwent a
      clinical examination to detect dementia. Univariate, bivariate, and multivariate
      logistic regression analyses were done. RESULTS: The whole population had a mean
      age of 72.4 years (+/-5.2) and was mostly male, married, and non-educated.
      Hypertension, arthritis, and gastrointestinal diseases were the main health
      conditions reported in the past medical history. Smoking was important while
      alcohol consumption was rare. Social network was high. Forty-five patients
      (8.87%) had dementia. In the multivariate model, only advanced age, education,
      epilepsy, and family history of dementia were independently associated with
      dementia. CONCLUSION: The risk factors identified are also found in developed
      countries confirming their role in dementia. It is important to take dementia
      into consideration in Senegal and to sensitize the community for prevention.

PMID- 22590477
TI  - Cerebral small vessel disease: cognition, mood, daily functioning, and imaging
      findings from a small pilot sample.
AB  - Cerebral small vessel disease, a leading cause of cognitive decline, is
      considered a relatively homogeneous disease process, and it can co-occur with
      Alzheimer's disease. Clinical reports of magnetic resonance imaging
      (MRI)/computed tomography and single photon emission computed tomography (SPECT)
      imaging and neuropsychology testing for a small pilot sample of 14 patients are
      presented to illustrate disease characteristics through findings from structural
      and functional imaging and cognitive assessment. Participants showed some
      decreases in executive functioning, attention, processing speed, and memory
      retrieval, consistent with previous literature. An older subgroup showed lower
      age-corrected scores at a single time point compared to younger participants.
      Performance on a computer-administered cognitive measure showed a slight overall
      decline over a period of 8-28 months. For a case study with mild neuropsychology
      findings, the MRI report was normal while the SPECT report identified perfusion
      abnormalities. Future research can test whether advances in imaging analysis
      allow for identification of cerebral small vessel disease before changes are
      detected in cognition.

PMID- 22590478
TI  - Ethical challenges in paediatric clinical trials in multiple sclerosis.
AB  - Children and adolescents with multiple sclerosis (MS) are reported to show high
      rates of relapse early in the course of the disease as well as cognitive
      deterioration over time. Immunomodulatory therapies developed for adult MS
      patients are currently the standard first-line agents for most paediatric MS
      patients. Available data indicate that the three interferon-beta preparations and
      glatiramer acetate are safe and well tolerated in children and adolescents with
      MS, and provide preliminary indications of efficacy in terms of relapse rate
      reduction. However, these treatments are only partly effective and their routes
      of administration can be bothersome, particularly for children. Emerging
      therapies for MS offer promise for improved disease control and long-term
      clinical outcome, with the advantage of an oral administration for some of them.
      The future approval of these new medications requires clinical trial
      consideration of such therapies in the paediatric population. Many of these new
      agents carry a higher risk for serious adverse events with increased toxicity and
      still undefined long-term side effects. There are ethical issues as well as
      issues related to feasibility that must be borne in mind when planning
      investigation trials for new pharmacological agents in the paediatric population,
      including immunological maturity, key period of exposure to numerous community
      acquired infections, neurodevelopmental factors, in addition to short-term and
      long-term age-related toxicities. Furthermore, the lack of a large enough
      paediatric MS population worldwide limits some designs and the feasibility of
      participation in all the studies. Emerging new therapies have the potential to
      optimize the care of both paediatric and adult patients with MS. Future treatment
      trials in children and adolescents with MS will require a multicentre design,
      definition and selection of key outcome measures, and identification of the most
      promising therapies. Risks versus benefits of each specific treatment should be
      weighed and comprehensively discussed.

PMID- 22590479
TI  - Glycoproteins as targets of autoantibodies in CNS inflammation: MOG and more.
AB  - B cells and antibodies constitute an important element in different inflammatory
      diseases of the central nervous system (CNS). Autoantibodies can serve as a
      biomarker to identify disease subgroups and may in addition contribute to the
      pathogenic process. One candidate autoantigen for multiple sclerosis (MS) is
      myelin oligodendrocyte glycoprotein (MOG). MOG is localized at the outermost
      surface of myelin in the CNS and has been the focus of extensive research for
      more than 30 years. Its role as an important autoantigen for T cells and as a
      target of demyelinating autoantibodies has been established in several variants
      of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The
      literature regarding antibodies to MOG in MS patients is confusing and
      contradictory. Recent studies, however, have described high levels of antibodies
      to conformationally correct MOG in pediatric acquired demyelination, both acute
      disseminated encephalomyelitis (ADEM) and MS. In adult MS, such antibodies are
      rarely found and then only at low levels. In this review, we summarize key
      findings from animal models and patient studies, discuss challenges in detecting
      anti-MOG antibodies in patients and present recent approaches to identifying new
      autoantigens in MS.

PMID- 22590480
TI  - Erythropoietin: still on the neuroprotection road.
AB  - Acute stroke is one of the major causes of death and disabilities. Since the
      1980s many clinical studies have been conducted to evaluate neuroprotective
      approaches to treat this important brain vascular event. However, to date the
      only drug approved (recombinant tissue plasminogen activator [rtPA]) represents a
      thrombolytic, nonneuroprotective approach. An important neuroprotective strategy
      is based on erythropoietin (EPO). Exogenously administered EPO exhibits
      neuroprotective effects in numerous animal models, through the activation of anti
      apoptotic, anti-oxidant and anti-inflammatory pathways as well as through the
      stimulation of angiogenic and neurogenic events. The capability of EPO to cross
      the blood-brain barrier after systemic administration and its effective
      therapeutic window are advantages for human acute stroke therapy. However, a
      multicenter stroke trial where recombinant human EPO (rhEPO) was combined with
      rtPA had negative outcomes. The present paper reviews the EPO neuroprotective
      strategy and its mechanisms in ischemic stroke and in other human nervous system
      diseases.

PMID- 22590481
TI  - Neurostimulation for chronic cluster headache.
AB  - Neurostimulation techniques for the treatment of primary headache syndromes,
      particularly of chronic cluster headache, have received much interest in recent
      years. Occipital nerve stimulation (ONS) has yielded favourable clinical results
      and, despite the limited numbers of published cases, is becoming a routine
      treatment for refractory chronic cluster headache in specialized centres.
      Meanwhile, other promising techniques such as spinal cord stimulation (SCS) or
      sphenopalate ganglion stimulation have emerged. In this article the current state
      of clinical research for neurostimulation techniques for chronic cluster headache
      is reviewed.

PMID- 22590483
TI  - Comparative cost efficiency across the European G5 countries of originators and a
      biosimilar erythropoiesis-stimulating agent to manage chemotherapy-induced anemia
      in patients with cancer.
AB  - OBJECTIVES: To evaluate the comparative cost efficiency across the European Union
      G5 countries of the erythropoiesis-stimulating agents (ESAs) epoetin alpha
      (originator [Eprex(r)] and biosimilar [Binocrit(r)]; once weekly), epoetin beta
      (NeoRecormon(r); once weekly), and darbepoetin alpha (Aranesp(r); once weekly or
      once every 3 weeks) under different scenarios of fixed and weight-based dosing in
      the management of chemotherapy-induced anemia. METHODS: Direct costs of ESA
      treatment were calculated for one patient with cancer undergoing chemotherapy
      (six cycles at 3-week intervals) with ESA initiated at week 4 and continued for
      15 weeks. Five scenarios were developed under fixed and weight-based dosing:
      continuous standard dose for 15 weeks; sustained dose escalation to 1.5* or
      double the standard dose at week 7, continued for 12 weeks; and discontinued dose
      escalation to 1.5* or double the standard dose at week 7 for a 3-week period,
      then 9 weeks of standard dose. RESULTS: Under fixed dosing, the average cost of
      biosimilar epoetin alpha treatment across scenarios was ?4643 (30,000 IU) or
      ?6178 (40,000 IU). Corresponding estimates were ?7168 for originator epoetin
      alpha, ?7389 for epoetin beta, ?8299 for darbepoetin alpha once weekly, and ?9221
      for darbepoetin alpha once every 3 weeks. Under weight-based dosing, the average
      cost of biosimilar epoetin alpha treatment across scenarios was ?4726.
      Corresponding estimates were ?5484 for originator epoetin alpha, ?5652 for
      epoetin beta, and ?8465 for both darbepoetin alpha once weekly and once every
      three weeks. CONCLUSION: Managing chemotherapy-induced anemia with biosimilar
      epoetin alpha is consistently cost efficient over treatment with originator
      epoetin alpha, epoetin beta, and darbepoetin alpha under both fixed and weight
      based dosing scenarios.

PMID- 22590484
TI  - Exemestane in the prevention setting.
AB  - Aromatase inhibitors are well-established therapies in the neoadjuvant, adjuvant
      and metastatic settings for breast cancer. In adjuvant trials, this class of
      drugs has shown preventative properties by decreasing the rate of contralateral
      breast cancer. Recently, the National Cancer Institute of Canada Clinical Trials
      Group MAP.3 study evaluated exemestane as a breast cancer prevention agent for
      women with specified higher risks of developing breast cancer. We review the
      history of exemestane and evaluate the available evidence of its use for breast
      cancer prevention.

PMID- 22590485
TI  - Beta-adrenergic blocking drugs in breast cancer: a perspective review.
AB  - The purpose of this review is to present the preclinical, epidemiological and
      clinical data relevant to the association between beta-blockers and breast cancer
      progression. Preclinical studies have shown that beta-adrenergic receptor (beta
      AR) signalling can inhibit multiple cellular processes involved in breast cancer
      progression and metastasis, including extracellular matrix invasion, expression
      of inflammatory and chemotactic cytokines, angiogenesis and tumour immune
      responses. This has led to the hypothesis that the commonly prescribed class of
      beta-AR antagonist drugs (beta-blockers) may favourably impact cancer
      progression. A number of recent pharmacoepidemiological studies have examined the
      association between beta-blocker exposure and breast cancer progression. The
      results from these studies have suggested a potential role for targeting the beta
      AR pathway in breast cancer patients. Larger observational studies are, however,
      required to confirm these results. Questions regarding the type of beta-blocker,
      predictive biomarkers or tumour characteristics, appropriate treatment paradigms
      and, most importantly, efficacy must also be answered in randomized clinical
      studies before beta-blockers can be considered a therapeutic option for patients
      with breast cancer.

PMID- 22590487
TI  - Improving survival and limiting toxicity: latest advances in treating human
      epidermal growth factor receptor 2 overexpressing breast cancer.
AB  - In recent years, new strategies for the treatment of breast cancer have focused
      on extensive target identification and understanding the expression, regulation
      and function of critical signaling pathways involved in breast cancer initiation
      and progression. This has led to significant progress in developing and
      understanding human epidermal growth factor receptor 2 (HER2)-targeted therapies,
      which in turn, has translated into significant increases in median survival for
      patients with HER2-overexpressing breast cancer. It is becoming increasingly
      difficult to make specific recommendations for the optimal treatment of HER2
      overexpressing breast cancer since the field is evolving so rapidly. However,
      despite the many randomized trials that have been undertaken showing improvement
      in survival, the current standard treatment for HER2-overexpressing breast cancer
      continues to revolve around the addition of chemotherapy to a HER2-targeted
      agent, which in turn, carries substantial toxicities. This article reviews agents
      that have recently been investigated to treat HER2-overexpressing breast cancers.
      The goal is ultimately to increase the magnitude and duration of response to
      trastuzumab-based treatment while minimizing toxicity. Studies addressing length
      of therapy duration, the superiority and side-effect profile of the different
      biological drug combinations, and determination of biomarkers of resistance to
      HER2 therapy will be instrumental in decreasing morbidity and mortality for
      patients with HER2-overexpressing breast cancer.

PMID- 22590486
TI  - Poor-prognosis estrogen receptor- positive disease: present and future clinical
      solutions.
AB  - Use of chemotherapy for patients with estrogen receptor (ER)-positive breast
      cancer has been a conflicting issue. Recent studies have identified predictive
      markers allowing identification of poor-prognosis ER-positive breast cancers in
      need of more aggressive therapy. In general, tumours belonging to the so-called
      luminal B class, tumours expressing a high Ki67, human epidermal growth factor
      receptor 2 (HER-2) overexpression or a high score on the Oncotype DX gene
      expression profile reveal a poor prognosis compared with ER-rich tumours of the
      luminal A class. In contrast, recent studies have shown these tumours,
      contrasting tumours of the luminal A class, to benefit from more aggressive
      anthracycline-containing chemotherapy including a taxane. In the case of
      metastatic disease, patients with HER-2-positive, ER-positive tumours may benefit
      from having endocrine therapy and an anti-HER-2 agent administered in
      combination.

PMID- 22590491
TI  - DYNAMO-HIA--a Dynamic Modeling tool for generic Health Impact Assessments.
AB  - BACKGROUND: Currently, no standard tool is publicly available that allows
      researchers or policy-makers to quantify the impact of policies using
      epidemiological evidence within the causal framework of Health Impact Assessment
      (HIA). A standard tool should comply with three technical criteria (real-life
      population, dynamic projection, explicit risk-factor states) and three usability
      criteria (modest data requirements, rich model output, generally accessible) to
      be useful in the applied setting of HIA. With DYNAMO-HIA (Dynamic Modeling for
      Health Impact Assessment), we introduce such a generic software tool specifically
      designed to facilitate quantification in the assessment of the health impacts of
      policies. METHODS AND RESULTS: DYNAMO-HIA quantifies the impact of user-specified
      risk-factor changes on multiple diseases and in turn on overall population
      health, comparing one reference scenario with one or more intervention scenarios.
      The Markov-based modeling approach allows for explicit risk-factor states and
      simulation of a real-life population. A built-in parameter estimation module
      ensures that only standard population-level epidemiological evidence is required,
      i.e. data on incidence, prevalence, relative risks, and mortality. DYNAMO-HIA
      provides a rich output of summary measures--e.g. life expectancy and disease-free
      life expectancy--and detailed data--e.g. prevalences and mortality/survival rates
      -by age, sex, and risk-factor status over time. DYNAMO-HIA is controlled via a
      graphical user interface and is publicly available from the internet, ensuring
      general accessibility. We illustrate the use of DYNAMO-HIA with two example
      applications: a policy causing an overall increase in alcohol consumption and
      quantifying the disease-burden of smoking. CONCLUSION: By combining modest data
      needs with general accessibility and user friendliness within the causal
      framework of HIA, DYNAMO-HIA is a potential standard tool for health impact
      assessment based on epidemiologic evidence.

PMID- 22590493
TI  - Quantifying social influence in an online cultural market.
AB  - We revisit experimental data from an online cultural market in which 14,000 users
      interact to download songs, and develop a simple model that can explain seemingly
      complex outcomes. Our results suggest that individual behavior is characterized
      by a two-step process--the decision to sample and the decision to download a
      song. Contrary to conventional wisdom, social influence is material to the first
      step only. The model also identifies the role of placement in mediating social
      signals, and suggests that in this market with anonymous feedback cues, social
      influence serves an informational rather than normative role.

PMID- 22590492
TI  - Prostaglandin I2 signaling drives Th17 differentiation and exacerbates
      experimental autoimmune encephalomyelitis.
AB  - BACKGROUND: Prostaglandin I(2) (PGI(2)), a lipid mediator currently used in
      treatment of human disease, is a critical regulator of adaptive immune responses.
      Although PGI(2) signaling suppressed Th1 and Th2 immune responses, the role of
      PGI(2) in Th17 differentiation is not known. METHODOLOGY/PRINCIPAL FINDINGS: In
      mouse CD4(+)CD62L(+) naive T cell culture, the PGI(2) analogs iloprost and
      cicaprost increased IL-17A and IL-22 protein production and Th17 differentiation
      in vitro. This effect was augmented by IL-23 and was dependent on PGI(2) receptor
      IP signaling. In mouse bone marrow-derived CD11c(+) dendritic cells (BMDCs),
      PGI(2) analogs increased the ratio of IL-23/IL-12, which is correlated with
      increased ability of BMDCs to stimulate naive T cells for IL-17A production.
      Moreover, IP knockout mice had delayed onset of a Th17-associated neurological
      disease, experimental autoimmune encephalomyelitis (EAE), and reduced
      infiltration of IL-17A-expressing mononuclear cells in the spinal cords compared
      to wild type mice. These results suggest that PGI(2) promotes in vivo Th17
      responses. CONCLUSION: The preferential stimulation of Th17 differentiation by IP
      signaling may have important clinical implications as PGI(2) and its analogs are
      commonly used to treat human pulmonary hypertension.

PMID- 22590494
TI  - Molecular characterisation of long-acting insulin analogues in comparison with
      human insulin, IGF-1 and insulin X10.
AB  - AIMS/HYPOTHESIS: There is controversy with respect to molecular characteristics
      of insulin analogues. We report a series of experiments forming a comprehensive
      characterisation of the long acting insulin analogues, glargine and detemir, in
      comparison with human insulin, IGF-1, and the super-mitogenic insulin, X10.
      METHODS: We measured binding of ligands to membrane-bound and solubilised
      receptors, receptor activation and mitogenicity in a number of cell types.
      RESULTS: Detemir and glargine each displayed a balanced affinity for insulin
      receptor (IR) isoforms A and B. This was also true for X10, whereas IGF-1 had a
      higher affinity for IR-A than IR-B. X10 and glargine both exhibited a higher
      relative IGF-1R than IR binding affinity, whereas detemir displayed an IGF-1R:IR
      binding ratio of <= 1. Ligands with high relative IGF-1R affinity also had high
      affinity for IR/IGF-1R hybrid receptors. In general, the relative binding
      affinities of the analogues were reflected in their ability to phosphorylate the
      IR and IGF-1R. Detailed analysis revealed that X10, in contrast to the other
      ligands, seemed to evoke a preferential phosphorylation of juxtamembrane and
      kinase domain phosphorylation sites of the IR. Sustained phosphorylation was only
      observed from the IR after stimulation with X10, and after stimulation with IGF-1
      from the IGF-1R. Both X10 and glargine showed an increased mitogenic potency
      compared to human insulin in cells expressing many IGF-1Rs, whereas only X10
      showed increased mitogenicity in cells expressing many IRs. CONCLUSIONS: Detailed
      analysis of receptor binding, activation and in vitro mitogenicity indicated no
      molecular safety concern with detemir.

PMID- 22590495
TI  - Exploring statistical and population aspects of network complexity.
AB  - The characterization and the definition of the complexity of objects is an
      important but very difficult problem that attracted much interest in many
      different fields. In this paper we introduce a new measure, called network
      diversity score (NDS), which allows us to quantify structural properties of
      networks. We demonstrate numerically that our diversity score is capable of
      distinguishing ordered, random and complex networks from each other and, hence,
      allowing us to categorize networks with respect to their structural complexity.
      We study 16 additional network complexity measures and find that none of these
      measures has similar good categorization capabilities. In contrast to many other
      measures suggested so far aiming for a characterization of the structural
      complexity of networks, our score is different for a variety of reasons. First,
      our score is multiplicatively composed of four individual scores, each assessing
      different structural properties of a network. That means our composite score
      reflects the structural diversity of a network. Second, our score is defined for
      a population of networks instead of individual networks. We will show that this
      removes an unwanted ambiguity, inherently present in measures that are based on
      single networks. In order to apply our measure practically, we provide a
      statistical estimator for the diversity score, which is based on a finite number
      of samples.

PMID- 22590496
TI  - Allocating scarce resources strategically--an evaluation and discussion of the
      Global Fund's pattern of disbursements.
AB  - BACKGROUND: The Global Fund is under pressure to improve its rationing of
      financial support. This study describes the GF's pattern of disbursements in
      relation to total health expenditure (THE), government health expenditure (GHE),
      income status and the burden of HIV/AIDS, TB and malaria. It also examines the
      potential for recipient countries to increase domestic public financing for
      health. METHODS: This is a cross-sectional study of 104 countries that received
      Global Fund disbursements in 2009. It analyses data on Global Fund disbursements;
      health financing indicators; government revenue and expenditure; and burden of
      disease. FINDINGS: Global Fund disbursements made up 0.37% of THE across all 104
      countries; but with considerable country variation ranging from 0.002% to 53.4%.
      Global Fund disbursements to government amounted to 0.47% of GHE across the 104
      countries, but again with considerable variation (in three countries more than
      half of GHE was based on Global Fund support). Although the Global Fund provides
      progressively more funding for lower income countries on average, there is much
      variation at the country such that here was no correlation between per capita GF
      disbursements and per capita THE, nor between per capita GF disbursement to
      government and per capita GHE. There was only a slight positive correlation
      between per capita GF disbursement and burden of disease. Several countries with
      a high degree of 'financial dependency' upon the Fund have the potential to
      increase levels of domestic financing for health. DISCUSSION: The Global Fund can
      improve its targeting of resources so that it better matches the pattern of
      global need. To do this it needs to: a) reduce the extent to which funds are
      allocated on a demand-driven basis; and b) align its funding model to broader
      health systems financing and patterns of health expenditure beyond the three
      diseases.

PMID- 22590497
TI  - Maternal antibody transmission in relation to mother fluctuating asymmetry in a
      long-lived colonial seabird: the yellow-legged gull Larus michahellis.
AB  - Female birds transfer antibodies to their offspring via the egg yolk, thus
      possibly providing passive immunity against infectious diseases to which
      hatchlings may be exposed, thereby affecting their fitness. It is nonetheless
      unclear whether the amount of maternal antibodies transmitted into egg yolks
      varies with female quality and egg laying order. In this paper, we investigated
      the transfer of maternal antibodies against type A influenza viruses (anti-AIV
      antibodies) by a long-lived colonial seabird, the yellow-legged gull (Larus
      michahellis), in relation to fluctuating asymmetry in females, i.e. the random
      deviation from perfect symmetry in bilaterally symmetric morphological and
      anatomical traits. In particular, we tested whether females with greater
      asymmetry transmitted fewer antibodies to their eggs, and whether within-clutch
      variation in yolk antibodies varied according to the maternal level of
      fluctuating asymmetry. We found that asymmetric females were in worse physical
      condition, produced fewer antibodies, and transmitted lower amounts of antibodies
      to their eggs. We also found that, within a given clutch, yolk antibody level
      decreased with egg laying order, but this laying order effect was more pronounced
      in clutches laid by the more asymmetric females. Overall, our results support the
      hypothesis that maternal quality interacts with egg laying order in determining
      the amount of maternal antibodies transmitted to the yolks. They also highlight
      the usefulness of fluctuating asymmetry as a sensitive indicator of female
      quality and immunocompetence in birds.

PMID- 22590498
TI  - Patient organizations' funding from pharmaceutical companies: is disclosure
      clear, complete and accessible to the public? An Italian survey.
AB  - BACKGROUND: Many patients' and consumers' organizations accept drug industry
      funding to support their activities. As drug companies and patient groups move
      closer, disclosure become essential for transparency, and the internet could be a
      useful means of making sponsorship information accessible to the public. This
      survey aims to assess the transparency of a large group of Italian patient and
      consumer groups and a group of pharmaceutical companies, focusing on their
      websites. METHODOLOGY/PRINCIPAL FINDINGS: Patient and consumer groups were
      selected from those stated to be sponsored by a group of pharmaceutical companies
      on their websites. The websites were examined using two forms with principal
      (name of drug companies providing funds, amount of funding) and secondary
      indicators of transparency (section where sponsors are disclosed, update of
      sponsorship). Principal indicators were applied independently by two reviewers to
      the patient and consumer groups' websites. Discordances were solved by
      discussion. One hundred fifty-seven Italian patient and consumer groups and 17
      drug companies were considered. Thirteen drug companies (76%) named at least one
      group funded, on their Italian websites. Of these, four (31%) indicated the
      activities sponsored and two (15%) the amount of funding. Of the 157 patient and
      consumer groups, 46 (29%) named at least one pharmaceutical company as providing
      funds. Three (6%) reported the amount of funding, 25 (54%) the activities funded,
      none the proportion of income derived from drug companies. Among the groups
      naming pharmaceutical company sponsors, 15 (33%) declared them in a dedicated
      section, five (11%) on the home page, the others in the financial report or other
      sections. CONCLUSIONS/SIGNIFICANCE: Disclosure of funds is scarce on Italian
      patient and consumer groups' websites. The levels of transparency need to be
      improved. Disclosure of patient and consumer groups provided with funds is
      frequent on Italian pharmaceutical companies' websites, but information are often
      not complete.

PMID- 22590499
TI  - Pre-whaling genetic diversity and population ecology in eastern Pacific gray
      whales: insights from ancient DNA and stable isotopes.
AB  - Commercial whaling decimated many whale populations, including the eastern
      Pacific gray whale, but little is known about how population dynamics or ecology
      differed prior to these removals. Of particular interest is the possibility of a
      large population decline prior to whaling, as such a decline could explain the ~5
      fold difference between genetic estimates of prior abundance and estimates based
      on historical records. We analyzed genetic (mitochondrial control region) and
      isotopic information from modern and prehistoric gray whales using serial
      coalescent simulations and Bayesian skyline analyses to test for a pre-whaling
      decline and to examine prehistoric genetic diversity, population dynamics and
      ecology. Simulations demonstrate that significant genetic differences observed
      between ancient and modern samples could be caused by a large, recent population
      bottleneck, roughly concurrent with commercial whaling. Stable isotopes show
      minimal differences between modern and ancient gray whale foraging ecology. Using
      rejection-based Approximate Bayesian Computation, we estimate the size of the
      population bottleneck at its minimum abundance and the pre-bottleneck abundance.
      Our results agree with previous genetic studies suggesting the historical size of
      the eastern gray whale population was roughly three to five times its current
      size.

PMID- 22590500
TI  - A single nucleotide polymorphism within the novel sex-linked testis-specific
      retrotransposed PGAM4 gene influences human male fertility.
AB  - BACKGROUND: The development of novel fertilization treatments, including in vitro
      fertilization and intracytoplasmic injection, has made pregnancy possible
      regardless of the level of activity of the spermatozoa; however, the etiology of
      male-factor infertility is poorly understood. Multiple studies, primarily through
      the use of transgenic animals, have contributed to a list of candidate genes that
      may affect male infertility in humans. We examined single nucleotide
      polymorphisms (SNPs) as a cause of male infertility in an analysis of
      spermatogenesis-specific genes. METHODS AND FINDING: We carried out the
      prevalence of SNPs in the coding region of phosphoglycerate mutase 4 (PGAM4) on
      the X chromosome by the direct sequencing of PCR-amplified DNA from male
      patients. Using RT-PCR and western blot analyses, we identified that PGAM4 is a
      functional retrogene that is expressed predominantly in the testes and is
      associated with male infertility. PGAM4 is expressed in post-meiotic stages,
      including spermatids and spermatozoa in the testes, and the principal piece of
      the flagellum and acrosome in ejaculated spermatozoa. A case-control study
      revealed that 4.5% of infertile patients carry the G75C polymorphism, which
      causes an amino acid substitution in the encoded protein. Furthermore, an assay
      for enzymatic activity demonstrated that this polymorphism decreases the enzyme's
      activity both in vitro and in vivo. CONCLUSION: These results suggest that PGAM4,
      an X-linked retrogene, is a fundamental gene in human male reproduction and may
      escape meiotic sex chromosome inactivation. These findings provide fresh insight
      into elucidating the mechanisms of male infertility.

PMID- 22590501
TI  - European American stratification in ovarian cancer case control data: the utility
      of genome-wide data for inferring ancestry.
AB  - We investigated the ability of several principal components analysis (PCA)-based
      strategies to detect and control for population stratification using data from a
      multi-center study of epithelial ovarian cancer among women of European-American
      ethnicity. These include a correction based on an ancestry informative markers
      (AIMs) panel designed to capture European ancestral variation and corrections
      utilizing un-thinned genome-wide SNP data; case-control samples were drawn from
      four geographically distinct North-American sites. The AIMs-only and genome-wide
      first principal components (PC1) both corresponded to the previously described
      North or Northwest-Southeast axis of European variation. We found that the genome
      wide PCA captured this primary dimension of variation more precisely and
      identified additional axes of genome-wide variation of relevance to epithelial
      ovarian cancer. Associations evident between the genome-wide PCs and study site
      corroborate North American immigration history and suggest that undiscovered
      dimensions of variation lie within Northern Europe. The structure captured by the
      genome-wide PCA was also found within control individuals and did not reflect the
      case-control variation present in the data. The genome-wide PCA highlighted three
      regions of local LD, corresponding to the lactase (LCT) gene on chromosome 2, the
      human leukocyte antigen system (HLA) on chromosome 6 and to a common inversion
      polymorphism on chromosome 8. These features did not compromise the efficacy of
      PCs from this analysis for ancestry control. This study concludes that although
      AIMs panels are a cost-effective way of capturing population structure, genome
      wide data should preferably be used when available.

PMID- 22590502
TI  - Single DermaVir immunization: dose-dependent expansion of precursor/memory T
      cells against all HIV antigens in HIV-1 infected individuals.
AB  - BACKGROUND: The GIHU004 study was designed to evaluate the safety and
      immunogenicity of three doses of DermaVir immunization in HIV-infected subjects
      on fully suppressive combination antiretroviral therapy (cART).
      METHODOLOGY/PRINCIPAL FINDINGS: This first-in-human dose escalation study was
      conducted with three topical DermaVir doses targeted to epidermal Langerhans
      cells to express fifteen HIV antigens in draining lymph nodes: 0.1 mg DNA
      targeted to two, 0.4 mg and 0.8 mg DNA targeted to four lymph nodes.
      Particularly, in the medium dose cohort 0.1 mg DNA was targeted per draining
      lymph node via ~8 million Langerhans cells located in 80 cm(2) epidermis area.
      The 28-days study with 48-week safety follow-up evaluated HIV-specific T cell
      responses against Gag p17, Gag p24 and Gag p15, Tat and Rev antigens. DermaVir
      associated side effects were mild, transient and not dose-dependent. Boosting of
      HIV-specific effector CD4(+) and CD8(+) T cells expressing IFN-gamma and IL-2 was
      detected against several antigens in every subject of the medium dose cohort. The
      striking result was the dose-dependent expansion of HIV-specific precursor/memory
      T cells with high proliferation capacity. In low, medium and high dose cohorts
      this HIV-specific T cell population increased by 325-, 136,202 and 50,759 counts
      after 4 weeks, and by 3,899, 9,878 and 18,382 counts after one year,
      respectively, compared to baseline. CONCLUSIONS/SIGNIFICANCE: Single immunization
      with the DermaVir candidate therapeutic vaccine was safe and immunogenic in HIV
      infected individuals. Based on the potent induction of Gag, Tat and Rev-specific
      memory T cells, especially in the medium dose cohort, we speculate that DermaVir
      boost T cell responses specific to all the 15 HIV antigens expressed from the
      single DNA. For durable immune reactivity repeated DermaVir immunization might be
      required since the frequency of DermaVir-boosted HIV-specific memory T cells
      decreased during the 48-week follow up. TRIAL REGISTRATION: ClinicalTrial.gov
      NCT00712530.

PMID- 22590503
TI  - Viral diversity and diversification of major non-structural genes vif, vpr, vpu,
      tat exon 1 and rev exon 1 during primary HIV-1 subtype C infection.
AB  - To assess the level of intra-patient diversity and evolution of HIV-1C non
      structural genes in primary infection, viral quasispecies obtained by single
      genome amplification (SGA) at multiple sampling timepoints up to 500 days post
      seroconversion (p/s) were analyzed. The mean intra-patient diversity was 0.11%
      (95% CI; 0.02 to 0.20) for vif, 0.23% (95% CI; 0.08 to 0.38) for vpr, 0.35% (95%
      CI; -0.05 to 0.75) for vpu, 0.18% (95% CI; 0.01 to 0.35) for tat exon 1 and 0.30%
      (95% CI; 0.02 to 0.58) for rev exon 1 during the time period 0 to 90 days p/s.
      The intra-patient diversity increased gradually in all non-structural genes over
      the first year of HIV-1 infection, which was evident from the vif mean intra
      patient diversity of 0.46% (95% CI; 0.28 to 0.64), vpr 0.44% (95% CI; 0.24 to
      0.64), vpu 0.84% (95% CI; 0.55 to 1.13), tat exon 1 0.35% (95% CI; 0.14 to 0.56 )
      and rev exon 1 0.42% (95% CI; 0.18 to 0.66) during the time period of 181 to 500
      days p/s. There was a statistically significant increase in viral diversity for
      vif (p = 0.013) and vpu (p = 0.002). No associations between levels of viral
      diversity within the non-structural genes and HIV-1 RNA load during primary
      infection were found. The study details the dynamics of the non-structural viral
      genes during the early stages of HIV-1C infection.

PMID- 22590504
TI  - Baicalin improves survival in a murine model of polymicrobial sepsis via
      suppressing inflammatory response and lymphocyte apoptosis.
AB  - BACKGROUND: An imbalance between overwhelming inflammation and lymphocyte
      apoptosis is the main cause of high mortality in patients with sepsis. Baicalin,
      the main active ingredient of the Scutellaria root, exerts anti-inflammatory,
      anti-apoptotic, and even antibacterial properties in inflammatory and infectious
      diseases. However, the therapeutic effect of baicalin on polymicrobial sepsis
      remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: Polymicrobial sepsis was induced
      by cecal ligation and puncture (CLP) in C57BL/6 mice. Mice were infused with
      baicalin intraperitoneally at 1 h, 6 h and 12 h after CLP. Survival rates were
      assessed over the subsequent 8 days. Bacterial burdens in blood and peritoneal
      cavity were calculated to assess the bacterial clearance. Neutrophil count in
      peritoneal lavage fluid was also calculated. Injuries to the lung and liver were
      detected by hematoxylin and eosin staining. Levels of cytokines, including tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10 and IL-17, in blood and
      peritoneum were measured by enzyme-linked immunosorbent assay. Adaptive immune
      function was assessed by apoptosis of lymphocytes in the thymus and counts of
      different cell types in the spleen. Baicalin significantly enhanced bacterial
      clearance and improved survival of septic mice. The number of neutrophils in
      peritoneal lavage fluid was reduced by baicalin. Less neutrophil infiltration of
      the lung and liver in baicalin-treated mice was associated with attenuated
      injuries to these organs. Baicalin significantly reduced the levels of
      proinflammatory cytokines but increased the level of anti-inflammatory cytokine
      in blood and peritoneum. Apoptosis of CD3(+) T cell was inhibited in the thymus.
      The numbers of CD4(+), CD8(+) T lymphocytes and dendritic cells (DCs) were
      higher, while the number of CD4(+)CD25(+) regulatory T cells was lower in the
      baicalin group compared with the CLP group. CONCLUSIONS/SIGNIFICANCE: Baicalin
      improves survival of mice with polymicrobial sepsis, and this may be attributed
      to its antibacterial property as well as its anti-inflammatory and anti-apoptotic
      effects.

PMID- 22590505
TI  - Automatic extraction of nuclei centroids of mouse embryonic cells from
      fluorescence microscopy images.
AB  - Accurate identification of cell nuclei and their tracking using three dimensional
      (3D) microscopic images is a demanding task in many biological studies. Manual
      identification of nuclei centroids from images is an error-prone task, sometimes
      impossible to accomplish due to low contrast and the presence of noise.
      Nonetheless, only a few methods are available for 3D bioimaging applications,
      which sharply contrast with 2D analysis, where many methods already exist. In
      addition, most methods essentially adopt segmentation for which a reliable
      solution is still unknown, especially for 3D bio-images having juxtaposed cells.
      In this work, we propose a new method that can directly extract nuclei centroids
      from fluorescence microscopy images. This method involves three steps: (i) Pre
      processing, (ii) Local enhancement, and (iii) Centroid extraction. The first step
      includes two variations: first variation (Variant-1) uses the whole 3D pre
      processed image, whereas the second one (Variant-2) modifies the preprocessed
      image to the candidate regions or the candidate hybrid image for further
      processing. At the second step, a multiscale cube filtering is employed in order
      to locally enhance the pre-processed image. Centroid extraction in the third step
      consists of three stages. In Stage-1, we compute a local characteristic ratio at
      every voxel and extract local maxima regions as candidate centroids using a ratio
      threshold. Stage-2 processing removes spurious centroids from Stage-1 results by
      analyzing shapes of intensity profiles from the enhanced image. An iterative
      procedure based on the nearest neighborhood principle is then proposed to combine
      if there are fragmented nuclei. Both qualitative and quantitative analyses on a
      set of 100 images of 3D mouse embryo are performed. Investigations reveal a
      promising achievement of the technique presented in terms of average sensitivity
      and precision (i.e., 88.04% and 91.30% for Variant-1; 86.19% and 95.00% for
      Variant-2), when compared with an existing method (86.06% and 90.11%), originally
      developed for analyzing C. elegans images.

PMID- 22590506
TI  - More stable productivity of semi natural grasslands than sown pastures in a
      seasonally dry climate.
AB  - In the Neotropics the predominant pathway to intensify productivity is generally
      thought to be to convert grasslands to sown pastures, mostly in monoculture. This
      article examines how above-ground net primary productivity (ANPP) in semi-natural
      grasslands and sown pastures in Central America respond to rainfall by: (i)
      assessing the relationships between ANPP and accumulated rainfall and indices of
      rainfall distribution, (ii) evaluating the variability of ANPP between and within
      seasons, and (iii) estimating the temporal stability of ANPP. We conducted
      sequential biomass harvests during 12 periods of 22 days and related those to
      rainfall. There were significant relationships between ANPP and cumulative
      rainfall in 22-day periods for both vegetation types and a model including a
      linear and quadratic term explained 74% of the variation in the data. There was
      also a significant correlation between ANPP and the number of rainfall events for
      both vegetation types. Sown pastures had higher ANPP increments per unit rainfall
      and higher ANPP at the peak of the rainy season than semi-natural grasslands. In
      contrast, semi-natural grasslands showed higher ANPP early in the dry season. The
      temporal stability of ANPP was higher in semi-natural grasslands than in the sown
      pastures in the dry season and over a whole annual cycle. Our results reveal
      that, contrary to conventional thinking amongst pasture scientists, there appears
      to be no increase in ANPP arising from replacing semi-natural grasslands with
      sown pastures under prevailing pasture management practices in seasonally dry
      climates, while the temporal distribution of ANPP is more even in semi-natural
      grasslands. Neither sown pastures nor semi-natural grasslands are productive
      towards the end of the dry season, indicating the potential importance of the
      widespread practice of retaining tree cover in pastures.

PMID- 22590507
TI  - Factors determining sensitivity and resistance of tumor cells to arsenic
      trioxide.
AB  - Previously, arsenic trioxide showed impressive regression rates of acute
      promyelocytic leukemia. Here, we investigated molecular determinants of
      sensitivity and resistance of cell lines of different tumor types towards arsenic
      trioxide. Arsenic trioxide was the most cytotoxic compound among 8 arsenicals
      investigated in the NCI cell line panel. We correlated transcriptome-wide
      microarray-based mRNA expression to the IC(50) values for arsenic trioxide by
      bioinformatic approaches (COMPARE and hierarchical cluster analyses, Ingenuity
      signaling pathway analysis). Among the identified pathways were signaling routes
      for p53, integrin-linked kinase, and actin cytoskeleton. Genes from these
      pathways significantly predicted cellular response to arsenic trioxide. Then, we
      analyzed whether classical drug resistance factors may also play a role for
      arsenic trioxide. Cell lines transfected with cDNAs for catalase, thioredoxin, or
      the anti-apoptotic bcl-2 gene were more resistant to arsenic trioxide than mock
      vector transfected cells. Multidrug-resistant cells overexpressing the MDR1, MRP1
      or BCRP genes were not cross-resistant to arsenic trioxide. Our approach revealed
      that response of tumor cells towards arsenic trioxide is multi-factorial.

PMID- 22590508
TI  - Dissociation between mature phenotype and impaired transmigration in dendritic
      cells from heparanase-deficient mice.
AB  - To reach the lymphatics, migrating dendritic cells (DCs) need to interact with
      the extracellular matrix (ECM). Heparanase, a mammalian endo-beta-D
      glucuronidase, specifically degrades heparan sulfate proteoglycans ubiquitously
      associated with the cell surface and ECM. The role of heparanase in the
      physiology of bone marrow-derived DCs was studied in mutant heparanase knock-out
      (Hpse-KO) mice. Immature DCs from Hpse-KO mice exhibited a more mature phenotype;
      however their transmigration was significantly delayed, but not completely
      abolished, most probably due to the observed upregulation of MMP-14 and CCR7.
      Despite their mature phenotype, uptake of beads was comparable and uptake of
      apoptotic cells was more efficient in DCs from Hpse-KO mice. Heparanase is an
      important enzyme for DC transmigration. Together with CCR7 and its ligands, and
      probably MMP-14, heparanase controls DC trafficking.

PMID- 22590510
TI  - Protecting persistent dynamic oceanographic features: transboundary conservation
      efforts are needed for the critically endangered Balearic shearwater.
AB  - The protection of key areas for biodiversity at sea is not as widespread as on
      land and research investment is necessary to identify biodiversity hotspots in
      the open ocean. Spatially explicit conservation measures such as the creation of
      representative networks of marine protected areas (MPAs) is a critical step
      towards the conservation and management of marine ecosystems, as well as to
      improve public awareness. Conservation efforts in ecologically rich and
      threatened ecosystems are specially needed. This is particularly urgent for the
      Mediterranean marine biodiversity, which includes highly mobile marine
      vertebrates. Here, we studied the at sea distribution of one of the most
      endangered Mediterranean seabird, the critically endangered Balearic shearwater
      Puffinus mauretanicus. Present knowledge, from vessel-based surveys, suggests
      that this species has a coastal distribution over the productive Iberian shelf in
      relation to the distribution of their main prey, small pelagic fish. We used
      miniaturised satellite transmitters to determine the key marine areas of the
      southern population of Balearic shearwaters breeding on Eivissa and spot the
      spatial connections between breeding and key marine areas. Our tracking study
      indicates that Balearic shearwaters do not only forage along the Iberian
      continental shelf but also in more distant marine areas along the North African
      coast, in particular W of Algeria, but also NE coast of Morocco. Birds
      recurrently visit these shelf areas at the end of the breeding season. Species
      distribution modelling identified chlorophyll a as the most important
      environmental variable in defining those oceanographic features characterizing
      their key habitats in the western Mediterranean. We identified persistent
      oceanographic features across time series available in the study area and discuss
      our results within the current conservation scenario in relation to the ecology
      of the species.

PMID- 22590509
TI  - Triggering of the dsRNA sensors TLR3, MDA5, and RIG-I induces CD55 expression in
      synovial fibroblasts.
AB  - BACKGROUND: CD55 (decay-accelerating factor) is a complement-regulatory protein
      highly expressed on fibroblast-like synoviocytes (FLS). CD55 is also a ligand for
      CD97, an adhesion-type G protein-coupled receptor abundantly present on
      leukocytes. Little is known regarding the regulation of CD55 expression in FLS.
      METHODS: FLS isolated from arthritis patients were stimulated with pro
      inflammatory cytokines and Toll-like receptor (TLR) ligands. Transfection with
      polyinosinic-polycytidylic acid (poly(I:C)) and 5'-triphosphate RNA were used to
      activate the cytoplasmic double-stranded (ds)RNA sensors melanoma differentiation
      associated gene 5 (MDA5) and retinoic acid-inducible gene-I (RIG-I). CD55
      expression, cell viability, and binding of CD97-loaded beads were quantified by
      flow cytometry. RESULTS: CD55 was expressed at equal levels on FLS isolated from
      patients with rheumatoid arthritis (RA), osteoarthritis, psoriatic arthritis and
      spondyloarthritis. CD55 expression in RA FLS was significantly induced by IL
      1beta and especially by the TLR3 ligand poly(I:C). Activation of MDA5 and RIG-I
      also enhanced CD55 expression. Notably, activation of MDA5 dose-dependently
      induced cell death, while triggering of TLR3 or RIG-I had a minor effect on
      viability. Upregulation of CD55 enhanced the binding capacity of FLS to CD97
      loaded beads, which could be blocked by antibodies against CD55. CONCLUSIONS:
      Activation of dsRNA sensors enhances the expression of CD55 in cultured FLS,
      which increases the binding to CD97. Our findings suggest that dsRNA promotes the
      interaction between FLS and CD97-expressing leukocytes.

PMID- 22590511
TI  - Leadership in orchestra emerges from the causal relationships of movement
      kinematics.
AB  - Non-verbal communication enables efficient transfer of information among people.
      In this context, classic orchestras are a remarkable instance of interaction and
      communication aimed at a common aesthetic goal: musicians train for years in
      order to acquire and share a non-linguistic framework for sensorimotor
      communication. To this end, we recorded violinists' and conductors' movement
      kinematics during execution of Mozart pieces, searching for causal relationships
      among musicians by using the Granger Causality method (GC). We show that the
      increase of conductor-to-musicians influence, together with the reduction of
      musician-to-musician coordination (an index of successful leadership) goes in
      parallel with quality of execution, as assessed by musical experts' judgments.
      Rigorous quantification of sensorimotor communication efficacy has always been
      complicated and affected by rather vague qualitative methodologies. Here we
      propose that the analysis of motor behavior provides a potentially interesting
      tool to approach the rather intangible concept of aesthetic quality of music and
      visual communication efficacy.

PMID- 22590512
TI  - Chilling-dependent release of seed and bud dormancy in peach associates to common
      changes in gene expression.
AB  - Reproductive meristems and embryos display dormancy mechanisms in specialized
      structures named respectively buds and seeds that arrest the growth of perennial
      plants until environmental conditions are optimal for survival. Dormancy shows
      common physiological features in buds and seeds. A genotype-specific period of
      chilling is usually required to release dormancy by molecular mechanisms that are
      still poorly understood. In order to find common transcriptional pathways
      associated to dormancy release, we analyzed the chilling-dependent expression in
      embryos of certain genes that were previously found related to dormancy in flower
      buds of peach. We propose the presence of short and long-term dormancy events
      affecting respectively the germination rate and seedling development by
      independent mechanisms. Short periods of chilling seem to improve germination in
      an abscisic acid-dependent manner, whereas the positive effect of longer cold
      treatments on physiological dwarfing coincides with the accumulation of
      phenylpropanoids in the seed.

PMID- 22590513
TI  - Implementation of anaphylaxis management guidelines: a register-based study.
AB  - BACKGROUND: Anaphylaxis management guidelines recommend the use of intramuscular
      adrenaline in severe reactions, complemented by antihistamines and corticoids;
      secondary prevention includes allergen avoidance and provision of self-applicable
      first aid drugs. Gaps between recommendations and their implementation have been
      reported, but only in confined settings. Hence, we analysed nation-wide data on
      the management of anaphylaxis, evaluating the implementation of guidelines.
      METHODS: Within the anaphylaxis registry, allergy referral centres across
      Germany, Austria and Switzerland provided data on severe anaphylaxis cases. Based
      on patient records, details on reaction circumstances, diagnostic workup and
      treatment were collected via online questionnaire. Report of anaphylaxis through
      emergency physicians allowed for validation of registry data. RESULTS: 2114
      severe anaphylaxis patients from 58 centres were included. 8% received adrenaline
      intravenously, 4% intramuscularly; 50% antihistamines, and 51% corticoids.
      Validation data indicated moderate underreporting of first aid drugs in the
      Registry. 20% received specific instructions at the time of the reaction; 81%
      were provided with prophylactic first aid drugs at any time. CONCLUSION: There is
      a distinct discrepancy between current anaphylaxis management guidelines and
      their implementation. To improve patient care, a revised approach for medical
      education and training on the management of severe anaphylaxis is warranted.

PMID- 22590515
TI  - Redundancy and cooperativity in the mechanics of compositely crosslinked
      filamentous networks.
AB  - The cytoskeleton of living cells contains many types of crosslinkers. Some
      crosslinkers allow energy-free rotations between filaments and others do not. The
      mechanical interplay between these different crosslinkers is an open issue in
      cytoskeletal mechanics. Therefore, we develop a theoretical framework based on
      rigidity percolation to study a generic filamentous system containing both
      stretching and bond-bending forces to address this issue. The framework involves
      both analytical calculations via effective medium theory and numerical
      simulations on a percolating triangular lattice with very good agreement between
      both. We find that the introduction of angle-constraining crosslinkers to a
      semiflexible filamentous network with freely rotating crosslinks can
      cooperatively lower the onset of rigidity to the connectivity percolation
      threshold-a result argued for years but never before obtained via effective
      medium theory. This allows the system to ultimately attain rigidity at the lowest
      concentration of material possible. We further demonstrate that introducing angle
      constraining crosslinks results in mechanical behaviour similar to just freely
      rotating crosslinked semflexible filaments, indicating redundancy and
      universality. Our results also impact upon collagen and fibrin networks in
      biological and bio-engineered tissues.

PMID- 22590514
TI  - Anti-inflammatory activities of inotilone from Phellinus linteus through the
      inhibition of MMP-9, NF-kappaB, and MAPK activation in vitro and in vivo.
AB  - Inotilone was isolated from Phellinus linteus. The anti-inflammatory effects of
      inotilone were studied by using lipopolysaccharide (LPS)-stimulated mouse
      macrophage RAW264.7 cells and lambda-carrageenan (Carr)-induced hind mouse paw
      edema model. Inotilone was tested for its ability to reduce nitric oxide (NO)
      production, and the inducible nitric oxide synthase (iNOS) expression. Inotilone
      was tested in the inhibitor of mitogen-activated protein kinase (MAPK)
      [extracellular signal-regulated protein kinase (ERK), c-Jun NH(2)-terminal kinase
      (JNK), p38], and nuclear factor-kappaB (NF-kappaB), matrix-metalloproteinase
      (MMP)-9 protein expressions in LPS-stimulated RAW264.7 cells. When RAW264.7
      macrophages were treated with inotilone together with LPS, a significant
      concentration-dependent inhibition of NO production was detected. Western
      blotting revealed that inotilone blocked the protein expression of iNOS, NF
      kappaB, and MMP-9 in LPS-stimulated RAW264.7 macrophages, significantly.
      Inotilone also inhibited LPS-induced ERK, JNK, and p38 phosphorylation. In in
      vivo tests, inotilone decreased the paw edema at the 4(th) and the 5(th) h after
      Carr administration, and it increased the activities of catalase (CAT),
      superoxide dismutase (SOD), and glutathione peroxidase (GPx). We also
      demonstrated that inotilone significantly attenuated the malondialdehyde (MDA)
      level in the edema paw at the 5(th) h after Carr injection. Inotilone decreased
      the NO and tumor necrosis factor (TNF-alpha) levels on serum at the 5(th) h after
      Carr injection. Western blotting revealed that inotilone decreased Carr-induced
      iNOS, cyclooxygenase-2 (COX-2), NF-kappaB, and MMP-9 expressions at the 5(th) h
      in the edema paw. An intraperitoneal (i.p.) injection treatment with inotilone
      diminished neutrophil infiltration into sites of inflammation, as did
      indomethacin (Indo). The anti-inflammatory activities of inotilone might be
      related to decrease the levels of MDA, iNOS, COX-2, NF-kappaB, and MMP-9 and
      increase the activities of CAT, SOD, and GPx in the paw edema through the
      suppression of TNF-alpha and NO. This study presents the potential utilization of
      inotilone, as a lead for the development of anti-inflammatory drugs.

PMID- 22590516
TI  - A comparison of three methods of Mendelian randomization when the genetic
      instrument, the risk factor and the outcome are all binary.
AB  - The method of instrumental variable (referred to as Mendelian randomization when
      the instrument is a genetic variant) has been initially developed to infer on a
      causal effect of a risk factor on some outcome of interest in a linear model.
      Adapting this method to nonlinear models, however, is known to be problematic. In
      this paper, we consider the simple case when the genetic instrument, the risk
      factor, and the outcome are all binary. We compare via simulations the usual two
      stages estimate of a causal odds-ratio and its adjusted version with a recently
      proposed estimate in the context of a clinical trial with noncompliance. In
      contrast to the former two, we confirm that the latter is (under some conditions)
      a valid estimate of a causal odds-ratio defined in the subpopulation of
      compliers, and we propose its use in the context of Mendelian randomization. By
      analogy with a clinical trial with noncompliance, compliers are those individuals
      for whom the presence/absence of the risk factor X is determined by the
      presence/absence of the genetic variant Z (i.e., for whom we would observe X = Z
      whatever the alleles randomly received at conception). We also recall and
      illustrate the huge variability of instrumental variable estimates when the
      instrument is weak (i.e., with a low percentage of compliers, as is typically the
      case with genetic instruments for which this proportion is frequently smaller
      than 10%) where the inter-quartile range of our simulated estimates was up to 18
      times higher compared to a conventional (e.g., intention-to-treat) approach. We
      thus conclude that the need to find stronger instruments is probably as important
      as the need to develop a methodology allowing to consistently estimate a causal
      odds-ratio.

PMID- 22590517
TI  - Understanding disease control: influence of epidemiological and economic factors.
AB  - We present a model of disease transmission on a regular and small world network
      and compare different control options. Comparison is based on a total cost of
      epidemic, including cost of palliative treatment of ill individuals and
      preventive cost aimed at vaccination or culling of susceptible individuals.
      Disease is characterized by pre-symptomatic phase, which makes detection and
      control difficult. Three general strategies emerge: global preventive treatment,
      local treatment within a neighborhood of certain size and only palliative
      treatment with no prevention. While the choice between the strategies depends on
      a relative cost of palliative and preventive treatment, the details of the local
      strategy and, in particular, the size of the optimal treatment neighborhood
      depend on the epidemiological factors. The required extent of prevention is
      proportional to the size of the infection neighborhood, but depends on time till
      detection and time till treatment in a non-nonlinear (power) law. The optimal
      size of control neighborhood is also highly sensitive to the relative cost,
      particularly for inefficient detection and control application. These results
      have important consequences for design of prevention strategies aiming at
      emerging diseases for which parameters are not nessecerly known in advance.

PMID- 22590518
TI  - Font size matters--emotion and attention in cortical responses to written words.
AB  - For emotional pictures with fear-, disgust-, or sex-related contents, stimulus
      size has been shown to increase emotion effects in attention-related event
      related potentials (ERPs), presumably reflecting the enhanced biological impact
      of larger emotion-inducing pictures. If this is true, size should not enhance
      emotion effects for written words with symbolic and acquired meaning. Here, we
      investigated ERP effects of font size for emotional and neutral words. While P1
      and N1 amplitudes were not affected by emotion, the early posterior negativity
      started earlier and lasted longer for large relative to small words. These
      results suggest that emotion-driven facilitation of attention is not necessarily
      based on biological relevance, but might generalize to stimuli with arbitrary
      perceptual features. This finding points to the high relevance of written
      language in today's society as an important source of emotional meaning.

PMID- 22590519
TI  - Reading speed, comprehension and eye movements while reading Japanese novels:
      evidence from untrained readers and cases of speed-reading trainees.
AB  - BACKGROUND: A growing body of evidence suggests that meditative training enhances
      perception and cognition. In Japan, the Park-Sasaki method of speed-reading
      involves organized visual training while forming both a relaxed and concentrated
      state of mind, as in meditation. The present study examined relationships between
      reading speed, sentence comprehension, and eye movements while reading short
      Japanese novels. In addition to normal untrained readers, three middle-level
      trainees and one high-level expert on this method were included for the two case
      studies. METHODOLOGY/PRINCIPAL FINDINGS: In Study 1, three of 17 participants
      were middle-level trainees on the speed-reading method. Immediately after reading
      each story once on a computer monitor, participants answered true or false
      questions regarding the content of the novel. Eye movements while reading were
      recorded using an eye-tracking system. Results revealed higher reading speed and
      lower comprehension scores in the trainees than in the untrained participants.
      Furthermore, eye-tracking data by untrained participants revealed multiple
      correlations between reading speed, accuracy and eye-movement measures, with
      faster readers showing shorter fixation durations and larger saccades in X than
      slower readers. In Study 2, participants included a high-level expert and 14
      untrained students. The expert showed higher reading speed and statistically
      comparable, although numerically lower, comprehension scores compared with the
      untrained participants. During test sessions this expert moved her eyes along a
      nearly straight horizontal line as a first pass, without moving her eyes over the
      whole sentence display as did the untrained students. CONCLUSIONS/SIGNIFICANCE:
      In addition to revealing correlations between speed, comprehension and eye
      movements in reading Japanese contemporary novels by untrained readers, we
      describe cases of speed-reading trainees regarding relationships between these
      variables. The trainees overall tended to show poor performance influenced by the
      speed-accuracy trade-off, although this trade-off may be reduced in the case of
      at least one high-level expert.

PMID- 22590520
TI  - Spatial pattern of standing timber value across the Brazilian Amazon.
AB  - The Amazon is a globally important system, providing a host of ecosystem services
      from climate regulation to food sources. It is also home to a quarter of all
      global diversity. Large swathes of forest are removed each year, and many models
      have attempted to predict the spatial patterns of this forest loss. The spatial
      patterns of deforestation are determined largely by the patterns of roads that
      open access to frontier areas and expansion of the road network in the Amazon is
      largely determined by profit seeking logging activities. Here we present
      predictions for the spatial distribution of standing value of timber across the
      Amazon. We show that the patterns of timber value reflect large-scale ecological
      gradients, determining the spatial distribution of functional traits of trees
      which are, in turn, correlated with timber values. We expect that understanding
      the spatial patterns of timber value across the Amazon will aid predictions of
      logging movements and thus predictions of potential future road developments.
      These predictions in turn will be of great use in estimating the spatial patterns
      of deforestation in this globally important biome.

PMID- 22590521
TI  - Maternal Wnt/beta-catenin signaling coactivates transcription through NF-kappaB
      binding sites during Xenopus axis formation.
AB  - Maternal Wnt/beta-Catenin signaling establishes a program of dorsal-specific gene
      expression required for axial patterning in Xenopus. We previously reported that
      a subset of dorsally expressed genes depends not only on Wnt/beta-Catenin
      stimulation, but also on a MyD88-dependent Toll-like receptor/IL1-receptor
      (TLR/IL1-R) signaling pathway. Here we show that these two signal transduction
      cascades converge in the nucleus to coactivate gene transcription in blastulae
      through a direct interaction between beta-Catenin and NF-kappaB proteins. A
      transdominant inhibitor of NF-kappaB, DeltaNIkappaBalpha, phenocopies loss of
      MyD88 protein function, implicating Rel/NF-kappaB proteins as selective
      activators of dorsal-specific gene expression. Sensitive axis formation assays in
      the embryo demonstrate that dorsalization by Wnt/beta-Catenin requires NF-kappaB
      protein activity, and vice versa. Xenopus nodal-related 3 (Xnr3) is one of the
      genes with dual beta-Catenin/NF-kappaB input, and a proximal NF-kappaB consensus
      site contributes to the regional activity of its promoter. We demonstrate in
      vitro binding of Xenopus beta-Catenin to several XRel proteins. This interaction
      is observed in vivo upon Wnt-stimulation. Finally, we show that a synthetic
      luciferase reporter gene responds to both endogenous and exogenous beta-Catenin
      levels in an NF-kappaB motif dependent manner. These results suggest that beta
      Catenin acts as a transcriptional co-activator of NF-kappaB-dependent
      transcription in frog primary embryonic cells.

PMID- 22590522
TI  - Sparse representation of brain aging: extracting covariance patterns from
      structural MRI.
AB  - An enhanced understanding of how normal aging alters brain structure is urgently
      needed for the early diagnosis and treatment of age-related mental diseases.
      Structural magnetic resonance imaging (MRI) is a reliable technique used to
      detect age-related changes in the human brain. Currently, multivariate pattern
      analysis (MVPA) enables the exploration of subtle and distributed changes of data
      obtained from structural MRI images. In this study, a new MVPA approach based on
      sparse representation has been employed to investigate the anatomical covariance
      patterns of normal aging. Two groups of participants (group 1:290 participants;
      group 2:56 participants) were evaluated in this study. These two groups were
      scanned with two 1.5 T MRI machines. In the first group, we obtained the
      discriminative patterns using a t-test filter and sparse representation step. We
      were able to distinguish the young from old cohort with a very high accuracy
      using only a few voxels of the discriminative patterns (group 1:98.4%; group
      2:96.4%). The experimental results showed that the selected voxels may be
      categorized into two components according to the two steps in the proposed
      method. The first component focuses on the precentral and postcentral gyri, and
      the caudate nucleus, which play an important role in sensorimotor tasks. The
      strongest volume reduction with age was observed in these clusters. The second
      component is mainly distributed over the cerebellum, thalamus, and right inferior
      frontal gyrus. These regions are not only critical nodes of the sensorimotor
      circuitry but also the cognitive circuitry although their volume shows a relative
      resilience against aging. Considering the voxels selection procedure, we suggest
      that the aging of the sensorimotor and cognitive brain regions identified in this
      study has a covarying relationship with each other.

PMID- 22590523
TI  - Effect of age on variability in the production of text-based global inferences.
AB  - As we age, our differences in cognitive skills become more visible, an effect
      especially true for memory and problem solving skills (i.e., fluid intelligence).
      However, by contrast with fluid intelligence, few studies have examined
      variability in measures that rely on one's world knowledge (i.e., crystallized
      intelligence). The current study investigated whether age increased the
      variability in text based global inference generation--a measure of crystallized
      intelligence. Global inference generation requires the integration of textual
      information and world knowledge and can be expressed as a gist or lesson.
      Variability in generating two global inferences for a single text was examined in
      young-old (62 to 69 years), middle-old (70 to 76 years) and old-old (77 to 94
      years) adults. The older two groups showed greater variability, with the middle
      elderly group being most variable. These findings suggest that variability may be
      a characteristic of both fluid and crystallized intelligence in aging.

PMID- 22590524
TI  - A carnivorous plant fed by its ant symbiont: a unique multi-faceted nutritional
      mutualism.
AB  - Scarcity of essential nutrients has led plants to evolve alternative nutritional
      strategies, such as myrmecotrophy (ant-waste-derived nutrition) and carnivory
      (invertebrate predation). The carnivorous plant Nepenthes bicalcarata grows in
      the Bornean peatswamp forests and is believed to have a mutualistic relationship
      with its symbiotic ant Camponotus schmitzi. However, the benefits provided by the
      ant have not been quantified. We tested the hypothesis of a nutritional
      mutualism, using foliar isotopic and reflectance analyses and by comparing
      fitness-related traits between ant-inhabited and uninhabited plants. Plants
      inhabited by C. schmitzi produced more leaves of greater area and nitrogen
      content than unoccupied plants. The ants were estimated to provide a 200%
      increase in foliar nitrogen to adult plants. Inhabited plants also produced more
      and larger pitchers containing higher prey biomass. C. schmitzi-occupied pitchers
      differed qualitatively in containing C. schmitzi wastes and captured large ants
      and flying insects. Pitcher abortion rates were lower in inhabited plants partly
      because of herbivore deterrence as herbivory-aborted buds decreased with ant
      occupation rate. Lower abortion was also attributed to ant nutritional service.
      The ants had higher delta(15)N values than any tested prey, and foliar delta(15)N
      increased with ant occupation rate, confirming their predatory behaviour and
      demonstrating their direct contribution to the plant-recycled N. We estimated
      that N. bicalcarata derives on average 42% of its foliar N from C. schmitzi
      wastes, (76% in highly-occupied plants). According to the Structure Independent
      Pigment Index, plants without C. schmitzi were nutrient stressed compared to both
      occupied plants, and pitcher-lacking plants. This attests to the physiological
      cost of pitcher production and poor nutrient assimilation in the absence of the
      symbiont. Hence C. schmitzi contributes crucially to the nutrition of N.
      bicalcarata, via protection of assimilatory organs, enhancement of prey capture,
      and myrmecotrophy. This combination of carnivory and myrmecotrophy represents an
      outstanding strategy of nutrient sequestration.

PMID- 22590526
TI  - How academic biologists and physicists view science outreach.
AB  - Scholars and pundits alike argue that U.S. scientists could do more to reach out
      to the general public. Yet, to date, there have been few systematic studies that
      examine how scientists understand the barriers that impede such outreach. Through
      analysis of 97 semi-structured interviews with academic biologists and physicists
      at top research universities in the United States, we classify the type and
      target audiences of scientists' outreach activities. Finally, we explore the
      narratives academic scientists have about outreach and its reception in the
      academy, in particular what they perceive as impediments to these activities. We
      find that scientists' outreach activities are stratified by gender and that
      university and disciplinary rewards as well as scientists' perceptions of their
      own skills have an impact on science outreach. Research contributions and
      recommendations for university policy follow.

PMID- 22590525
TI  - Hypocotyl transcriptome reveals auxin regulation of growth-promoting genes
      through GA-dependent and -independent pathways.
AB  - Many processes critical to plant growth and development are regulated by the
      hormone auxin. Auxin responses are initiated through activation of a
      transcriptional response mediated by the TIR1/AFB family of F-box protein auxin
      receptors as well as the AUX/IAA and ARF families of transcriptional regulators.
      However, there is little information on how auxin regulates a specific cellular
      response. To begin to address this question, we have focused on auxin regulation
      of cell expansion in the Arabidopsis hypocotyl. We show that auxin-mediated
      hypocotyl elongation is dependent upon the TIR1/AFB family of auxin receptors and
      degradation of AUX/IAA repressors. We also use microarray studies of elongating
      hypocotyls to show that a number of growth-associated processes are activated by
      auxin including gibberellin biosynthesis, cell wall reorganization and
      biogenesis, and others. Our studies indicate that GA biosynthesis is required for
      normal response to auxin in the hypocotyl but that the overall transcriptional
      auxin output consists of PIF-dependent and -independent genes. We propose that
      auxin acts independently from and interdependently with PIF and GA pathways to
      regulate expression of growth-associated genes in cell expansion.

PMID- 22590527
TI  - FKBP5 as a selection biomarker for gemcitabine and Akt inhibitors in treatment of
      pancreatic cancer.
AB  - We have recently shown that the immunophilin FKBP5 (also known as FKBP51) is a
      scaffolding protein that can enhance PHLPP-AKT interaction and facilitate PHLPP
      mediated dephosphorylation of Akt Ser473, negatively regulating Akt activation in
      vitro. Therefore, FKBP5 might function as a tumor suppressor, and levels of FKBP5
      would affect cell response to chemotherapy. In the current study, we have taken a
      step forward by using a pancreatic cancer xenograft mice model to show that down
      regulation of FKBP5 in shFKBP5 xenograft mice promotes tumor growth and
      resistance to gemcitabine, a phenomenon consistent with our previous findings in
      pancreatic cell lines. In addition, we also found that inhibitors targeting the
      Akt pathway, including PI3K inhibitor, Akt inhibitor and mTOR inhibitor had a
      different effect on sensitization to gemcitabine and other chemotherapeutic
      agents in cell lines, with a specific Akt inhibitor, triciribine, having the
      greatest sensitization effect. We then tested the hypothesis that addition of
      triciribine can sensitize gemcitabine treatment, especially in shFKBP5 pancreatic
      cancer xenograft mice. We found that combination treatment with gemcitabine and
      triciribine has a better effect on tumor inhibition than either drug alone
      (p<0.005) and that the inhibition effect is more significant in shFKBP5 xenograft
      mice than wt mice (p<0.05). These effects were correlated with level of Akt 473
      phosphorylation as well as proliferation rate, as indicated by Ki67 staining in
      xenograft tumor tissues. These results provide evidence in support of future
      clinical trials designed to tailor therapy based on our observations.

PMID- 22590528
TI  - The functions of grainy head-like proteins in animals and fungi and the evolution
      of apical extracellular barriers.
AB  - The Grainy head (GRH) family of transcription factors are crucial for the
      development and repair of epidermal barriers in all animals in which they have
      been studied. This is a high-level functional conservation, as the known
      structural and enzymatic genes regulated by GRH proteins differ between species
      depending on the type of epidermal barrier being formed. Interestingly, members
      of the CP2 superfamily of transcription factors, which encompasses the GRH and
      LSF families in animals, are also found in fungi--organisms that lack epidermal
      tissues. To shed light on CP2 protein function in fungi, we characterized a
      Neurospora crassa mutant lacking the CP2 member we refer to as grainy head-like
      (grhl). We show that Neurospora GRHL has a DNA-binding specificity similar to
      that of animal GRH proteins and dissimilar to that of animal LSF proteins.
      Neurospora grhl mutants are defective in conidial-spore dispersal due to an
      inability to remodel the cell wall, and we show that grhl mutants and the long
      known conidial separation-2 (csp-2) mutants are allelic. We then characterized
      the transcriptomes of both Neurospora grhl mutants and Drosophila grh mutant
      embryos to look for similarities in the affected genes. Neurospora grhl appears
      to play a role in the development and remodeling of the cell wall, as well as in
      the activation of genes involved in defense and virulence. Drosophila GRH is
      required to activate the expression of many genes involved in cuticular/epidermal
      barrier formation. We also present evidence that GRH plays a role in adult
      antimicrobial defense. These results, along with previous studies of animal GRH
      proteins, suggest the fascinating possibility that the apical extracellular
      barriers of some animals and fungi might share an evolutionary connection, and
      that the formation of physical barriers in the last common ancestor was under the
      control of a transcriptional code that included GRH-like proteins.

PMID- 22590529
TI  - High interstitial fluid pressure is associated with low tumour penetration of
      diagnostic monoclonal antibodies applied for molecular imaging purposes.
AB  - The human epithelial cell adhesion molecule (EpCAM) is highly expressed in a
      variety of clinical tumour entities. Although an antibody against EpCAM has
      successfully been used as an adjuvant therapy in colon cancer, this therapy has
      never gained wide-spread use. We have therefore investigated the possibilities
      and limitations for EpCAM as possible molecular imaging target using a panel of
      preclinical cancer models. Twelve human cancer cell lines representing six tumour
      entities were tested for their EpCAM expression by qPCR, flow cytometry analysis
      and immunocytochemistry. In addition, EpCAM expression was analyzed in vivo in
      xenograft models for tumours derived from these cells. Except for melanoma, all
      cell lines expressed EpCAM mRNA and protein when grown in vitro. Although they
      exhibited different mRNA levels, all cell lines showed similar EpCAM protein
      levels upon detection with monoclonal antibodies. When grown in vivo, the EpCAM
      expression was unaffected compared to in vitro except for the pancreatic
      carcinoma cell line 5072 which lost its EpCAM expression in vivo. Intravenously
      applied radio-labelled anti EpCAM MOC31 antibody was enriched in HT29 primary
      tumour xenografts indicating that EpCAM binding sites are accessible in vivo.
      However, bound antibody could only be immunohistochemically detected in the
      vicinity of perfused blood vessels. Investigation of the fine structure of the
      HT29 tumour blood vessels showed that they were immature and prone for higher
      fluid flux into the interstitial space. Consistent with this hypothesis, a higher
      interstitial fluid pressure of about 12 mbar was measured in the HT29 primary
      tumour via "wick-in-needle" technique which could explain the limited diffusion
      of the antibody into the tumour observed by immunohistochemistry.

PMID- 22590530
TI  - Regional brain responses in nulliparous women to emotional infant stimuli.
AB  - Infant cries and facial expressions influence social interactions and elicit
      caretaking behaviors from adults. Recent neuroimaging studies suggest that neural
      responses to infant stimuli involve brain regions that process rewards. However,
      these studies have yet to investigate individual differences in tendencies to
      engage or withdraw from motivationally relevant stimuli. To investigate this, we
      used event-related fMRI to scan 17 nulliparous women. Participants were presented
      with novel infant cries of two distress levels (low and high) and unknown infant
      faces of varying affect (happy, sad, and neutral) in a randomized, counter
      balanced order. Brain activation was subsequently correlated with scores on the
      Behavioral Inhibition System/Behavioral Activation System scale. Infant cries
      activated bilateral superior and middle temporal gyri (STG and MTG) and
      precentral and postcentral gyri. Activation was greater in bilateral temporal
      cortices for low- relative to high-distress cries. Happy relative to neutral
      faces activated the ventral striatum, caudate, ventromedial prefrontal, and
      orbitofrontal cortices. Sad versus neutral faces activated the precuneus, cuneus,
      and posterior cingulate cortex, and behavioral activation drive correlated with
      occipital cortical activations in this contrast. Behavioral inhibition correlated
      with activation in the right STG for high- and low-distress cries relative to
      pink noise. Behavioral drive correlated inversely with putamen, caudate, and
      thalamic activations for the comparison of high-distress cries to pink noise.
      Reward-responsiveness correlated with activation in the left precentral gyrus
      during the perception of low-distress cries relative to pink noise. Our findings
      indicate that infant cry stimuli elicit activations in areas implicated in
      auditory processing and social cognition. Happy infant faces may be encoded as
      rewarding, whereas sad faces activate regions associated with empathic
      processing. Differences in motivational tendencies may modulate neural responses
      to infant cues.

PMID- 22590531
TI  - Ca2+/calmodulin-dependent protein kinase kinase is not involved in hypothalamic
      AMP-activated protein kinase activation by neuroglucopenia.
AB  - Hypoglycemia and neuroglucopenia stimulate AMP-activated protein kinase (AMPK)
      activity in the hypothalamus and this plays an important role in the
      counterregulatory responses, i.e. increased food intake and secretion of
      glucagon, corticosterone and catecholamines. Several upstream kinases that
      activate AMPK have been identified including Ca(2+)/Calmodulin-dependent protein
      kinase kinase (CaMKK), which is highly expressed in neurons. However, the
      involvement of CaMKK in neuroglucopenia-induced activation of AMPK in the
      hypothalamus has not been tested. To determine whether neuroglucopenia-induced
      AMPK activation is mediated by CaMKK, we tested whether STO-609 (STO), a CaMKK
      inhibitor, would block the effects of 2-deoxy-D-glucose (2DG)-induced
      neuroglucopenia both ex vivo on brain sections and in vivo. Preincubation of rat
      brain sections with STO blocked KCl-induced alpha1 and alpha2-AMPK activation but
      did not affect AMPK activation by 2DG in the medio-basal hypothalamus. To confirm
      these findings in vivo, STO was pre-administrated intracerebroventricularly (ICV)
      in rats 30 min before 2DG ICV injection (40 umol) to induce neuroglucopenia. 2DG
      induced neuroglucopenia lead to a significant increase in glycemia and food
      intake compared to saline-injected control rats. ICV pre-administration of STO
      (5, 20 or 50 nmol) did not affect 2DG-induced hyperglycemia and food intake.
      Importantly, activation of hypothalamic alpha1 and alpha2-AMPK by 2DG was not
      affected by ICV pre-administration of STO. In conclusion, activation of
      hypothalamic AMPK by 2DG-induced neuroglucopenia is not mediated by CaMKK.

PMID- 22590532
TI  - Objective vs. self-reported physical activity and sedentary time: effects of
      measurement method on relationships with risk biomarkers.
AB  - PURPOSE: Imprecise measurement of physical activity variables might attenuate
      estimates of the beneficial effects of activity on health-related outcomes. We
      aimed to compare the cardiometabolic risk factor dose-response relationships for
      physical activity and sedentary behaviour between accelerometer- and
      questionnaire-based activity measures. METHODS: Physical activity and sedentary
      behaviour were assessed in 317 adults by 7-day accelerometry and International
      Physical Activity Questionnaire (IPAQ). Fasting blood was taken to determine
      insulin, glucose, triglyceride and total, LDL and HDL cholesterol concentrations
      and homeostasis model-estimated insulin resistance (HOMA(IR)). Waist
      circumference, BMI, body fat percentage and blood pressure were also measured.
      RESULTS: For both accelerometer-derived sedentary time (<100 counts.min(-1)) and
      IPAQ-reported sitting time significant positive (negative for HDL cholesterol)
      relationships were observed with all measured risk factors--i.e. increased
      sedentary behaviour was associated with increased risk (all p <= 0.01). However,
      for HOMA(IR) and insulin the regression coefficients were >50% lower for the IPAQ
      reported compared to the accelerometer-derived measure (p<0.0001 for both
      interactions). The relationships for moderate-to-vigorous physical activity
      (MVPA) and risk factors were less strong than those observed for sedentary
      behaviours, but significant negative relationships were observed for both
      accelerometer and IPAQ MVPA measures with glucose, and insulin and HOMA(IR)
      values (all p<0.05). For accelerometer-derived MVPA only, additional negative
      relationships were seen with triglyceride, total cholesterol and LDL cholesterol
      concentrations, BMI, waist circumference and percentage body fat, and a positive
      relationship was evident with HDL cholesterol (p = 0.0002). Regression
      coefficients for HOMA(IR), insulin and triglyceride were 43-50% lower for the
      IPAQ-reported compared to the accelerometer-derived MVPA measure (all p<=0.01).
      CONCLUSION: Using the IPAQ to determine sitting time and MVPA reveals some, but
      not all, relationships between these activity measures and metabolic and vascular
      disease risk factors. Using this self-report method to quantify activity can
      therefore underestimate the strength of some relationships with risk factors.

PMID- 22590533
TI  - Gametogenesis in the Pacific oyster Crassostrea gigas: a microarrays-based
      analysis identifies sex and stage specific genes.
AB  - BACKGROUND: The Pacific oyster Crassostrea gigas (Mollusca, Lophotrochozoa) is an
      alternative and irregular protandrous hermaphrodite: most individuals mature
      first as males and then change sex several times. Little is known about genetic
      and phenotypic basis of sex differentiation in oysters, and little more about the
      molecular pathways regulating reproduction. We have recently developed and
      validated a microarray containing 31,918 oligomers (Dheilly et al., 2011)
      representing the oyster transcriptome. The application of this microarray to the
      study of mollusk gametogenesis should provide a better understanding of the key
      factors involved in sex differentiation and the regulation of oyster
      reproduction. METHODOLOGY/PRINCIPAL FINDINGS: Gene expression was studied in
      gonads of oysters cultured over a yearly reproductive cycle. Principal component
      analysis and hierarchical clustering showed a significant divergence in gene
      expression patterns of males and females coinciding with the start of gonial
      mitosis. ANOVA analysis of the data revealed 2,482 genes differentially expressed
      during the course of males and/or females gametogenesis. The expression of 434
      genes could be localized in either germ cells or somatic cells of the gonad by
      comparing the transcriptome of female gonads to the transcriptome of stripped
      oocytes and somatic tissues. Analysis of the annotated genes revealed conserved
      molecular mechanisms between mollusks and mammals: genes involved in chromatin
      condensation, DNA replication and repair, mitosis and meiosis regulation,
      transcription, translation and apoptosis were expressed in both male and female
      gonads. Most interestingly, early expressed male-specific genes included bindin
      and a dpy-30 homolog and female-specific genes included foxL2, nanos homolog 3, a
      pancreatic lipase related protein, cd63 and vitellogenin. Further functional
      analyses are now required in order to investigate their role in sex
      differentiation in oysters. CONCLUSIONS/SIGNIFICANCE: This study allowed us to
      identify potential markers of early sex differentiation in the oyster C. gigas,
      an alternative hermaphrodite mollusk. We also provided new highly valuable
      information on genes specifically expressed by mature spermatozoids and mature
      oocytes.

PMID- 22590534
TI  - The gracilis myocutaneous free flap: a quantitative analysis of the
      fasciocutaneous blood supply and implications for autologous breast
      reconstruction.
AB  - BACKGROUND: Mastectomies are one of the most common surgical procedures in women
      of the developed world. The gracilis myocutaneous flap is favoured by many
      reconstructive surgeons due to the donor site profile and speed of dissection.
      The distal component of the longitudinal skin paddle of the gracilis myocutaneous
      flap is unreliable. This study quantifies the fasciocutaneous vascular
      territories of the gracilis flap and offers the potential to reconstruct breasts
      of all sizes. METHODS: Twenty-seven human cadaver dissections were performed and
      injected using lead oxide into the gracilis vascular pedicles, followed by
      radiographic studies to identify the muscular and fasciocutaneous perforator
      patterns. The vascular territories and choke zones were characterized
      quantitatively using the 'Lymphatic Vessel Analysis Protocol' (LVAP) plug-in for
      Image J(r) software. RESULTS: We found a step-wise decrease in the average vessel
      density from the upper to middle and lower thirds of both the gracilis muscle and
      the overlying skin paddle with a significantly higher average vessel density in
      the skin compared to the muscle. The average vessel width was greater in the
      muscle. Distal to the main pedicle, there were either one (7/27 cases), two
      (14/27 cases) or three (6/27 cases) minor pedicles. The gracilis angiosome was T
      shaped and the maximum cutaneous vascular territory for the main and first minor
      pedicle was 35 * 19 cm and 34 * 10 cm, respectively. CONCLUSION: Our findings
      support the concept that small volume breast reconstructions can be performed on
      suitable patients, based on septocutaneous perforators from the minor pedicle
      without the need to harvest any muscle, further reducing donor site morbidity.
      For large reconstructions, if a 'T' or tri-lobed flap with an extended vertical
      component is needed, it is important to establish if three territories are
      present. Flap reliability and size may be optimized following computed
      tomographic angiography and surgical delay.

PMID- 22590535
TI  - Insight into the stability of cross-beta amyloid fibril from VEALYL short peptide
      with molecular dynamics simulation.
AB  - Amyloid fibrils are found in many fatal neurodegenerative diseases such as
      Alzheimer's disease, Parkinson's disease, type II diabetes, and prion disease.
      The VEALYL short peptide from insulin has been confirmed to aggregate amyloid
      like fibrils. However, the aggregation mechanism of amyloid fibril is poorly
      understood. Here, we utilized molecular dynamics simulation to analyse the
      stability of VEALYL hexamer. The statistical results indicate that hydrophobic
      residues play key roles in stabilizing VEALYL hexamer. Single point and two
      linkage mutants confirmed that Val1, Leu4, and Tyr5 of VEALYL are key residues.
      The consistency of the results for the VEALYL oligomer suggests that the
      intermediate states might be trimer (3-0) and pentamer(3-2). These results can
      help us to obtain an insight into the aggregation mechanism of amyloid fibril.
      These methods can be used to study the stability of amyloid fibril from other
      short peptides.

PMID- 22590536
TI  - Integrated analysis of gene expression and tumor nuclear image profiles
      associated with chemotherapy response in serous ovarian carcinoma.
AB  - BACKGROUND: Small sample sizes used in previous studies result in a lack of
      overlap between the reported gene signatures for prediction of chemotherapy
      response. Although morphologic features, especially tumor nuclear morphology, are
      important for cancer grading, little research has been reported on quantitatively
      correlating cellular morphology with chemotherapy response, especially in a large
      data set. In this study, we have used a large population of patients to identify
      molecular and morphologic signatures associated with chemotherapy response in
      serous ovarian carcinoma. METHODOLOGY/PRINCIPAL FINDINGS: A gene expression model
      that predicts response to chemotherapy is developed and validated using a large
      scale data set consisting of 493 samples from The Cancer Genome Atlas (TCGA) and
      244 samples from an Australian report. An identified 227-gene signature achieves
      an overall predictive accuracy of greater than 85% with a sensitivity of
      approximately 95% and specificity of approximately 70%. The gene signature
      significantly distinguishes between patients with unfavorable versus favorable
      prognosis, when applied to either an independent data set (P = 0.04) or an
      external validation set (P<0.0001). In parallel, we present the production of a
      tumor nuclear image profile generated from 253 sample slides by characterizing
      patients with nuclear features (such as size, elongation, and roundness) in
      incremental bins, and we identify a morphologic signature that demonstrates a
      strong association with chemotherapy response in serous ovarian carcinoma.
      CONCLUSIONS: A gene signature discovered on a large data set provides robustness
      in accurately predicting chemotherapy response in serous ovarian carcinoma. The
      combination of the molecular and morphologic signatures yields a new
      understanding of potential mechanisms involved in drug resistance.

PMID- 22590537
TI  - A genome-wide siRNA screen to identify modulators of insulin sensitivity and
      gluconeogenesis.
AB  - BACKGROUND: Hepatic insulin resistance impairs insulin's ability to suppress
      hepatic glucose production (HGP) and contributes to the development of type 2
      diabetes (T2D). Although the interests to discover novel genes that modulate
      insulin sensitivity and HGP are high, it remains challenging to have a human cell
      based system to identify novel genes. METHODOLOGY/PRINCIPAL FINDINGS: To identify
      genes that modulate hepatic insulin signaling and HGP, we generated a human cell
      line stably expressing beta-lactamase under the control of the human glucose-6
      phosphatase (G6PC) promoter (AH-G6PC cells). Both beta-lactamase activity and
      endogenous G6PC mRNA were increased in AH-G6PC cells by a combination of
      dexamethasone and pCPT-cAMP, and reduced by insulin. A 4-gene High-Throughput
      Genomics assay was developed to concomitantly measure G6PC and pyruvate
      dehydrogenase-kinase-4 (PDK4) mRNA levels. Using this assay, we screened an siRNA
      library containing pooled siRNA targeting 6650 druggable genes and identified 614
      hits that lowered G6PC expression without increasing PDK4 mRNA levels. Pathway
      analysis indicated that siRNA-mediated knockdown (KD) of genes known to
      positively or negatively affect insulin signaling increased or decreased G6PC
      mRNA expression, respectively, thus validating our screening platform. A subset
      of 270 primary screen hits was selected and 149 hits were confirmed by target
      gene KD by pooled siRNA and 7 single siRNA for each gene to reduce G6PC
      expression in 4-gene HTG assay. Subsequently, pooled siRNA KD of 113 genes
      decreased PEPCK and/or PGC1alpha mRNA expression thereby demonstrating their role
      in regulating key gluconeogenic genes in addition to G6PC. Last, KD of 61 of the
      above 113 genes potentiated insulin-stimulated Akt phosphorylation, suggesting
      that they suppress gluconeogenic gene by enhancing insulin signaling.
      CONCLUSIONS/SIGNIFICANCE: These results support the proposition that the proteins
      encoded by the genes identified in our cell-based druggable genome siRNA screen
      hold the potential to serve as novel pharmacological targets for the treatment of
      T2D.

PMID- 22590538
TI  - Cholesterol-independent effects of methyl-beta-cyclodextrin on chemical synapses.
AB  - The cholesterol chelating agent, methyl-beta-cyclodextrin (MbetaCD), alters
      synaptic function in many systems. At crayfish neuromuscular junctions, MbetaCD
      is reported to reduce excitatory junctional potentials (EJPs) by impairing
      impulse propagation to synaptic terminals, and to have no postsynaptic effects.
      We examined the degree to which physiological effects of MbetaCD correlate with
      its ability to reduce cholesterol, and used thermal acclimatization as an
      alternative method to modify cholesterol levels. MbetaCD impaired impulse
      propagation and decreased EJP amplitude by 40% (P<0.05) in preparations from
      crayfish acclimatized to 14  degrees C but not from those acclimatized to 21 
      degrees C. The reduction in EJP amplitude in the cold-acclimatized group was
      associated with a 49% reduction in quantal content (P<0.05). MbetaCD had no
      effect on input resistance in muscle fibers but decreased sensitivity to the
      neurotransmitter L-glutamate in both warm- and cold-acclimatized groups. This
      effect was less pronounced and reversible in the warm-acclimatized group (90%
      reduction in cold, P<0.05; 50% reduction in warm, P<0.05). MbetaCD reduced
      cholesterol in isolated nerve and muscle from cold- and warm-acclimatized groups
      by comparable amounts (nerve: 29% cold, 25% warm; muscle: 20% cold, 18% warm;
      P<0.05). This effect was reversed by cholesterol loading, but only in the warm
      acclimatized group. Thus, effects of MbetaCD on glutamate-sensitivity correlated
      with its ability to reduce cholesterol, but effects on impulse propagation and
      resulting EJP amplitude did not. Our results indicate that MbetaCD can affect
      both presynaptic and postsynaptic properties, and that some effects of MbetaCD
      are unrelated to cholesterol chelation.

PMID- 22590540
TI  - Docking of LDCVs is modulated by lower intracellular [Ca2+] than priming.
AB  - Many regulatory steps precede final membrane fusion in neuroendocrine cells. Some
      parts of this preparatory cascade, including fusion and priming, are dependent on
      the intracellular Ca(2+) concentration ([Ca(2+)](i)). However, the functional
      implications of [Ca(2+)](i) in the regulation of docking remain elusive and
      controversial due to an inability to determine the modulatory effect of
      [Ca(2+)](i). Using a combination of TIRF-microscopy and electrophysiology we
      followed the movement of large dense core vesicles (LDCVs) close to the plasma
      membrane, simultaneously measuring membrane capacitance and [Ca(2+)](i). We found
      that a free [Ca(2+)](i) of 700 nM maximized the immediately releasable pool and
      minimized the lateral mobility of vesicles, which is consistent with a maximal
      increase of the pool size of primed LDCVs. The parameters that reflect docking,
      i.e. axial mobility and the fraction of LDCVs residing at the plasma membrane for
      less than 5 seconds, were strongly decreased at a free [Ca(2+)](i) of 500 nM.
      These results provide the first evidence that docking and priming occur at
      different free intracellular Ca(2+) concentrations, with docking efficiency being
      the most robust at 500 nM.

PMID- 22590539
TI  - Anatomical connectivity influences both intra- and inter-brain synchronizations.
AB  - Recent development in diffusion spectrum brain imaging combined to functional
      simulation has the potential to further our understanding of how structure and
      dynamics are intertwined in the human brain. At the intra-individual scale,
      neurocomputational models have already started to uncover how the human
      connectome constrains the coordination of brain activity across distributed brain
      regions. In parallel, at the inter-individual scale, nascent social neuroscience
      provides a new dynamical vista of the coupling between two embodied cognitive
      agents. Using EEG hyperscanning to record simultaneously the brain activities of
      subjects during their ongoing interaction, we have previously demonstrated that
      behavioral synchrony correlates with the emergence of inter-brain
      synchronization. However, the functional meaning of such synchronization remains
      to be specified. Here, we use a biophysical model to quantify to what extent
      inter-brain synchronizations are related to the anatomical and functional
      similarity of the two brains in interaction. Pairs of interacting brains were
      numerically simulated and compared to real data. Results show a potential
      dynamical property of the human connectome to facilitate inter-individual
      synchronizations and thus may partly account for our propensity to generate
      dynamical couplings with others.

PMID- 22590541
TI  - The development of the Problematic Online Gaming Questionnaire (POGQ).
AB  - BACKGROUND: Online gaming has become increasingly popular. However, this has led
      to concerns that these games might induce serious problems and/or lead to
      dependence for a minority of players. AIM: The aim of this study was to uncover
      and operationalize the components of problematic online gaming. METHODS: A total
      of 3415 gamers (90% males; mean age 21 years), were recruited through online
      gaming websites. A combined method of exploratory factor analysis (EFA) and
      confirmatory factor analysis (CFA) was applied. Latent profile analysis was
      applied to identify persons at-risk. RESULTS: EFA revealed a six-factor structure
      in the background of problematic online gaming that was also confirmed by a CFA.
      For the assessment of the identified six dimensions--preoccupation, overuse,
      immersion, social isolation, interpersonal conflicts, and withdrawal--the 18-item
      Problematic Online Gaming Questionnaire (POGQ) proved to be exceedingly suitable.
      Based on the latent profile analysis, 3.4% of the gamer population was considered
      to be at high risk, while another 15.2% was moderately problematic. CONCLUSIONS:
      The POGQ seems to be an adequate measurement tool for the differentiated
      assessment of gaming related problems on six subscales.

PMID- 22590542
TI  - Differential neuregulin 1 cleavage in the prefrontal cortex and hippocampus in
      schizophrenia and bipolar disorder: preliminary findings.
AB  - BACKGROUND: Neuregulin 1 (NRG1) is a key candidate susceptibility gene for both
      schizophrenia (SCZ) and bipolar disorder (BPD). The function of the NRG1
      transmembrane proteins is regulated by cleavage. Alteration of membrane bound
      NRG1 cleavage has been previously shown to be associated with behavioral
      impairments in mouse models lacking expression of NRG1-cleavage enzymes such as
      BACE1 and gamma secretase. We sought to determine whether alterations in NRG1
      cleavage and associated enzymes occur in patients with SCZ and BPD.
      METHODOLOGY/PRINCIPAL FINDINGS: Using human postmortem brain, we evaluated
      protein expression of NRG1 cleavage products and enzymes that cleave at the
      external (BACE1, ADAM17, ADAM19) and internal (PS1-gamma secretase) sides of the
      cell membrane. We used three different cohorts (Controls, SCZ and BPD) and two
      distinct brain regions: BA9-prefrontal cortex (Controls (n = 6), SCZ (n = 6) and
      BPD (n = 6)) and hippocampus (Controls (n = 5), SCZ (n = 6) and BPD (n = 6)). In
      BA9, the ratio of the NRG1 N-terminal fragment relative to full length was
      significantly upregulated in the SCZ cohort (Bonferroni test, p = 0.011). ADAM17
      was negatively correlated with full length NRG1 levels in the SCZ cohort (r = 
      0.926, p = 0.008). In the hippocampus we found significantly lower levels of a
      soluble 50 kDa NRG1 fragment in the two affected groups compared the control
      cohort (Bonferroni test, p = 0.0018). We also examined the relationship of
      specific symptomatology criteria with measures of NRG1 cleavage using the Bipolar
      Inventory of Signs and Symptoms Scale (BISS) and the Montgomery Asberg Depression
      Rating Scale (MADRS). Our results showed a positive correlation between ADAM19
      and psychosis (r = 0.595 p = 0.019); PS1 and mania (r = 0.535, p = 0.040); PS1
      and depression (r = 0.567, p = 0.027) in BA9, and BACE1 with anxiety (r = 0.608,
      p = 0.03) in the hippocampus. CONCLUSION/SIGNIFICANCE: Our preliminary findings
      suggest region-specific alterations in NRG1 cleavage in SCZ and BPD patients.
      These changes may be associated with specific symptoms in these psychiatric
      disorders.

PMID- 22590543
TI  - Risk factors for extended duration of acute diarrhea in young children.
AB  - OBJECTIVE AND BACKGROUND: We sought to identify predictors of extended duration
      of diarrhea in young children, which contributes substantially to the nearly 1
      1/2 million annual diarrheal deaths globally. METHODS: We followed 6-35 month old
      Nepalese children enrolled in the placebo-arm of a randomized controlled trial
      with 391 episodes of acute diarrhea from the day they were diagnosed until
      cessation of the episode. Using multiple logistic regression analysis, we
      identified independent risk factors for having diarrhea for more than 7 days
      after diagnosis. RESULTS: Infants had a 17 (95% CI 3.5, 83)-fold and toddlers (12
      to 23 month olds) a 9.9 (95% CI 2.1, 47)-fold higher odds of having such illness
      duration compared to the older children. Not being breastfed was associated with
      a 9.3 (95% CI 2.4, 35.7)-fold increase in the odds for this outcome. The odds
      also increased with increasing stool frequency. Furthermore, having diarrhea in
      the monsoon season also increased the risk of prolonged illness. CONCLUSION: We
      found that high stool frequency, not being breastfed, young age and acquiring
      diarrhea in the rainy season were risk factors for prolonged diarrhea. In
      populations such as ours, breastfeeding may be the most important modifiable risk
      factor for extended duration of diarrhea.

PMID- 22590544
TI  - International network for comparison of HIV neutralization assays: the NeutNet
      report II.
AB  - BACKGROUND: Neutralizing antibodies provide markers for vaccine-induced
      protective immunity in many viral infections. By analogy, HIV-1 neutralizing
      antibodies induced by immunization may well predict vaccine effectiveness.
      Assessment of neutralizing antibodies is therefore of primary importance, but is
      hampered by the fact that we do not know which assay(s) can provide measures of
      protective immunity. An international collaboration (NeutNet) involving 18
      different laboratories previously compared different assays using monoclonal
      antibodies (mAbs) and soluble CD4 (Phase I study). METHODS: In the present study
      (Phase II), polyclonal reagents were evaluated by 13 laboratories. Each
      laboratory evaluated nine plasmas against an 8 virus panel representing different
      genetic subtypes and phenotypes. TriMab, a mixture of three mAbs, was used as a
      positive control allowing comparison of the results with Phase I in a total of
      nine different assays. The assays used either uncloned virus produced in
      peripheral blood mononuclear cells (PBMCs) (Virus Infectivity Assays, VIA), or
      Env (gp160)-pseudotyped viruses (pseudoviruses, PSV) produced in HEK293T cells
      from molecular clones or from uncloned virus. Target cells included PBMC and
      genetically engineered cell lines in either single- or multiple-cycle infection
      format. Infection was quantified by using a range of assay read-outs including
      extra- or intra-cellular p24 antigen detection, luciferase, beta-galactosidase or
      green fluorescent protein (GFP) reporter gene expression. FINDINGS: Using TriMab,
      results of Phase I and Phase II were generally in agreement for six of the eight
      viruses tested and confirmed that the PSV assay is more sensitive than PBMC (p =
      0.014). Comparisons with the polyclonal reagents showed that sensitivities were
      dependent on both virus and plasma. CONCLUSIONS: Here we further demonstrate
      clear differences in assay sensitivities that were dependent on both the
      neutralizing reagent and the virus. Consistent with the Phase I study, we
      recommend parallel use of PSV and VIA for vaccine evaluation.

PMID- 22590545
TI  - A phylogenetic perspective on the evolution of Mediterranean teleost fishes.
AB  - The Mediterranean Sea is a highly diverse, highly studied, and highly impacted
      biogeographic region, yet no phylogenetic reconstruction of fish diversity in
      this area has been published to date. Here, we infer the timing and geographic
      origins of Mediterranean teleost species diversity using nucleotide sequences
      collected from GenBank. We assembled a DNA supermatrix composed of four
      mitochondrial genes (12S ribosomal DNA, 16S ribosomal DNA, cytochrome c oxidase
      subunit I and cytochrome b) and two nuclear genes (rhodopsin and recombination
      activating gene I), including 62% of Mediterranean teleost species plus 9
      outgroups. Maximum likelihood and Bayesian phylogenetic and dating analyses were
      calibrated using 20 fossil constraints. An additional 124 species were grafted
      onto the chronogram according to their taxonomic affinity, checking for the
      effects of taxonomic coverage in subsequent diversification analyses. We then
      interpreted the time-line of teleost diversification in light of Mediterranean
      historical biogeography, distinguishing non-endemic natives, endemics and exotic
      species. Results show that the major Mediterranean orders are of Cretaceous
      origin, specifically ~100-80 Mya, and most Perciformes families originated 80-50
      Mya. Two important clade origin events were detected. The first at 100-80 Mya,
      affected native and exotic species, and reflects a global diversification period
      at a time when the Mediterranean Sea did not yet exist. The second occurred
      during the last 50 Mya, and is noticeable among endemic and native species, but
      not among exotic species. This period corresponds to isolation of the
      Mediterranean from Indo-Pacific waters before the Messinian salinity crisis. The
      Mediterranean fish fauna illustrates well the assembly of regional faunas through
      origination and immigration, where dispersal and isolation have shaped the
      emergence of a biodiversity hotspot.

PMID- 22590546
TI  - A monoclonal antibody against p53 cross-reacts with processing bodies.
AB  - The p53 tumor suppressor protein is an important regulator of cell proliferation
      and apoptosis. p53 can be found in the nucleus and in the cytosol, and the
      subcellular location is key to control p53 function. In this work, we found that
      a widely used monoclonal antibody against p53, termed Pab 1801 (Pan antibody
      1801) yields a remarkable punctate signal in the cytoplasm of several cell lines
      of human origin. Surprisingly, these puncta were also observed in two independent
      p53-null cell lines. Moreover, the foci stained with the Pab 1801 were present in
      rat cells, although Pab 1801 recognizes an epitope that is not conserved in
      rodent p53. In contrast, the Pab 1801 nuclear staining corresponded to genuine
      p53, as it was upregulated by p53-stimulating drugs and absent in p53-null cells.
      We identified the Pab 1801 cytoplasmic puncta as P Bodies (PBs), which are
      involved in mRNA regulation. We found that, in several cell lines, including
      U2OS, WI38, SK-N-SH and HCT116, the Pab 1801 puncta strictly colocalize with PBs
      identified with specific antibodies against the PB components Hedls, Dcp1a, Xrn1
      or Rck/p54. PBs are highly dynamic and accordingly, the Pab 1801 puncta vanished
      when PBs dissolved upon treatment with cycloheximide, a drug that causes polysome
      stabilization and PB disruption. In addition, the knockdown of specific PB
      components that affect PB integrity simultaneously caused PB dissolution and the
      disappearance of the Pab 1801 puncta. Our results reveal a strong cross
      reactivity of the Pab 1801 with unknown PB component(s). This was observed upon
      distinct immunostaining protocols, thus meaning a major limitation on the use of
      this antibody for p53 imaging in the cytoplasm of most cell types of human or
      rodent origin.

PMID- 22590547
TI  - Human tears reveal insights into corneal neovascularization.
AB  - Corneal neovascularization results from the encroachment of blood vessels from
      the surrounding conjunctiva onto the normally avascular cornea. The aim of this
      study is to identify factors in human tears that are involved in development
      and/or maintenance of corneal neovascularization in humans. This could allow
      development of diagnostic tools for monitoring corneal neovascularization and
      combination monoclonal antibody therapies for its treatment. In an observational
      case-control study we enrolled a total of 12 patients with corneal
      neovascularization and 10 healthy volunteers. Basal tears along with reflex tears
      from the inferior fornix, superior fornix and using a corneal bath were collected
      along with blood serum samples. From all patients, ocular surface photographs
      were taken. Concentrations of the pro-angiogenic cytokines interleukin (IL)-6, IL
      8, Vascular Endothelial Growth Factor (VEGF), Monocyte Chemoattractant Protein 1
      (MCP-1) and Fas Ligand (FasL) were determined in blood and tear samples using a
      flow cytometric multiplex assay. Our results show that the concentration of pro
      angiogenic cytokines in human tears are significantly higher compared to their
      concentrations in serum, with highest levels found in basal tears. Interestingly,
      we could detect a significantly higher concentration of IL- 6, IL-8 and VEGF in
      localized corneal tears of patients with neovascularized corneas when compared to
      the control group. This is the first study of its kind demonstrating a
      significant difference of defined factors in tears from patients with
      neovascularized corneas as compared to healthy controls. These results provide
      the basis for future research using animal models to further substantiate the
      role of these cytokines in the establishment and maintenance of corneal
      neovascularization.

PMID- 22590548
TI  - Improved siderotic nodule detection in cirrhosis with susceptibility-weighted
      magnetic resonance imaging: a prospective study.
AB  - BACKGROUND: Hepatic cirrhosis is a common pathway of progressive liver
      destruction from multiple causes. Iron uptake can occur within the hepatic
      parenchyma or within the various nodules that form in a cirrhotic liver, termed
      siderotic nodules. Siderotic nodule formation has been shown to correlate with
      inflammatory activity, and while the relationship between siderotic nodule
      formation and malignancy remains unclear, iron distribution within hepatic
      nodules has known implications for the detection of hepatocellular carcinoma. We
      aimed to evaluate the role of abdominal susceptibility-weighted imaging in the
      detection of siderotic nodules in cirrhotic patients. METHODOLOGY/PRINCIPAL
      FINDINGS: Forty-six (46) cirrhotic patients with at least one siderotic nodule
      detected on previous imaging underwent both computed tomography and magnetic
      resonance imaging (T1-, T2-, T2*-, and susceptibility-weighted imaging) at 3.0
      Tesla. Imaging data was independently analyzed by two radiologists. Siderotic
      nodule count was determined for each modality and imaging sequence. For each
      magnetic resonance imaging technique, siderotic nodule conspicuity was assessed
      on a 3 point scale (1 = weak, 2 = moderate, 3 = strong). More nodules were
      detected by susceptibility weighted imaging (n = 2935) than any other technique,
      and significantly more than by T2* weighted imaging (n = 1696, p<0.0001). Lesion
      conspicuity was also highest with susceptibility-weighted imaging, with all
      nodules found to be moderate (n = 6) or strong (n = 40); a statistically
      significant difference (p<0.001). CONCLUSIONS: Susceptibility-weighted imaging
      had the greatest lesion conspicuity and detected the highest number of siderotic
      nodules suggesting it is the most sensitive imaging technique to detect siderotic
      nodules in cirrhotic patients.

PMID- 22590549
TI  - Ordered self-assembly mechanism of a spherical oncoprotein oligomer triggered by
      zinc removal and stabilized by an intrinsically disordered domain.
AB  - BACKGROUND: Self-assembly is a common theme in proteins of unrelated sequences or
      functions. The human papillomavirus E7 oncoprotein is an extended dimer with an
      intrinsically disordered domain, that can form large spherical oligomers. These
      are the major species in the cytosol of HPV transformed and cancerous cells. E7
      binds to a large number of targets, some of which lead to cell transformation.
      Thus, the assembly process not only is of biological relevance, but represents a
      model system to investigate a widely distributed mechanism. METHODOLOGY/PRINCIPAL
      FINDINGS: Using various techniques, we monitored changes in secondary, tertiary
      and quaternary structure in a time course manner. By applying a robust kinetic
      model developed by Zlotnik, we determined the slow formation of a monomeric "Z
      nucleus" after zinc removal, followed by an elongation phase consisting of
      sequential second-order events whereby one monomer is added at a time. This
      elongation process takes place at a strikingly slow overall average rate of one
      monomer added every 28 seconds at 20 uM protein concentration, strongly
      suggesting either a rearrangement of the growing complex after binding of each
      monomer or the existence of a "conformation editing" mechanism through which the
      monomer binds and releases until the appropriate conformation is adopted. The
      oligomerization determinant lies within its small 5 kDa C-terminal globular
      domain and, remarkably, the E7 N-terminal intrinsically disordered domain
      stabilizes the oligomer, preventing an insoluble amyloid route. CONCLUSION: We
      described a controlled ordered mechanism with features in common with soluble
      amyloid precursors, chaperones, and other spherical oligomers, thus sharing
      determining factors for symmetry, size and shape. In addition, such a controlled
      and discrete polymerization reaction provides a valuable tool for
      nanotechnological applications. Finally, its increased immunogenicity related to
      its supramolecular structure is the basis for the development of a promising
      therapeutic vaccine candidate for treating HPV cancerous lesions.

PMID- 22590550
TI  - Sustainable sources of biomass for bioremediation of heavy metals in waste water
      derived from coal-fired power generation.
AB  - Biosorption of heavy metals using dried algal biomass has been extensively
      described but rarely implemented. We contend this is because available algal
      biomass is a valuable product with a ready market. Therefore, we considered an
      alternative and practical approach to algal bioremediation in which algae were
      cultured directly in the waste water stream. We cultured three species of algae
      with and without nutrient addition in water that was contaminated with heavy
      metals from an Ash Dam associated with coal-fired power generation and tested
      metal uptake and bioremediation potential. All species achieved high
      concentrations of heavy metals (to 8% dry mass). Two key elements, V and As,
      reached concentrations in the biomass of 1543 mg.kg(-1) DW and 137 mg.kg(-1) DW.
      Growth rates were reduced by more than half in neat Ash Dam water than when
      nutrients were supplied in excess. Growth rate and bioconcentration were
      positively correlated for most elements, but some elements (e.g. Cd, Zn) were
      concentrated more when growth rates were lower, indicating the potential to
      tailor bioremediation depending on the pollutant. The cosmopolitan nature of the
      macroalgae studied, and their ability to grow and concentrate a suite of heavy
      metals from industrial wastes, highlights a clear benefit in the practical
      application of waste water bioremediation.

PMID- 22590551
TI  - High-frequency, low-magnitude vibration does not prevent bone loss resulting from
      muscle disuse in mice following botulinum toxin injection.
AB  - High-frequency, low-magnitude vibration enhances bone formation ostensibly by
      mimicking normal postural muscle activity. We tested this hypothesis by examining
      whether daily exposure to low-magnitude vibration (VIB) would maintain bone in a
      muscle disuse model with botulinum toxin type A (BTX). Female 16-18 wk old BALB/c
      mice (N = 36) were assigned to BTX-VIB, BTX-SHAM, VIB, or SHAM. BTX mice were
      injected with BTX (20 uL; 1 U/100 g body mass) into the left hindlimb posterior
      musculature. All mice were anaesthetized for 20 min/d, 5 d/wk, for 3 wk, and the
      left leg mounted to a holder. Through the holder, VIB mice received 45 Hz, +/-
      0.6 g sinusoidal acceleration without weight bearing. SHAM mice received no
      vibration. At baseline and 3 wk, muscle cross-sectional area (MCSA) and tibial
      bone properties (epiphysis, metaphysis and diaphysis) were assessed by in vivo
      micro-CT. Bone volume fraction in the metaphysis decreased 12 +/- 9% and 7 +/- 6%
      in BTX-VIB and BTX-SHAM, but increased in the VIB and SHAM. There were no
      differences in dynamic histomorphometry outcomes between BTX-VIB and BTX nor
      between VIB and SHAM. Thus, vibration did not prevent bone loss induced by a
      rapid decline in muscle activity nor produce an anabolic effect in normal mice.
      The daily loading duration was shorter than would be expected from postural
      muscle activity, and may have been insufficient to prevent bone loss. Based on
      the approach used in this study, vibration does not prevent bone loss in the
      absence of muscle activity induced by BTX.

PMID- 22590552
TI  - A CI-independent form of replicative inhibition: turn off of early replication of
      bacteriophage lambda.
AB  - Several earlier studies have described an unusual exclusion phenotype exhibited
      by cells with plasmids carrying a portion of the replication region of phage
      lambda. Cells exhibiting this inhibition phenotype (IP) prevent the plating of
      homo-immune and hybrid hetero-immune lambdoid phages. We have attempted to define
      aspects of IP, and show that it is directed to replambda phages. IP was observed
      in cells with plasmids containing a lambda DNA fragment including oop, encoding a
      short OOP micro RNA, and part of the lambda origin of replication, orilambda,
      defined by iteron sequences ITN1-4 and an adjacent high AT-rich sequence.
      Transcription of the intact oop sequence from its promoter, p(O) is required for
      IP, as are iterons ITN3-4, but not the high AT-rich portion of orilambda. The
      results suggest that IP silencing is directed to theta mode replication
      initiation from an infecting replambda genome, or an induced replambda prophage.
      Phage mutations suppressing IP, i.e., Sip, map within, or adjacent to cro or in
      O, or both. Our results for plasmid based IP suggest the hypothesis that there is
      a natural mechanism for silencing early theta-mode replication initiation, i.e.
      the buildup of lambda genomes with oop(+)orilambda(+) sequence.

PMID- 22590553
TI  - An in vivo cis-regulatory screen at the type 2 diabetes associated TCF7L2 locus
      identifies multiple tissue-specific enhancers.
AB  - Genome-wide association studies (GWAS) have repeatedly shown an association
      between non-coding variants in the TCF7L2 locus and risk for type 2 diabetes
      (T2D), implicating a role for cis-regulatory variation within this locus in
      disease etiology. Supporting this hypothesis, we previously localized complex
      regulatory activity to the TCF7L2 T2D-associated interval using an in vivo
      bacterial artificial chromosome (BAC) enhancer-trapping reporter strategy. To
      follow-up on this broad initial survey of the TCF7L2 regulatory landscape, we
      performed a fine-mapping enhancer scan using in vivo mouse transgenic reporter
      assays. We functionally interrogated approximately 50% of the sequences within
      the T2D-associated interval, utilizing sequence conservation within this 92-kb
      interval to determine the regulatory potential of all evolutionary conserved
      sequences that exhibited conservation to the non-eutherian mammal opossum.
      Included in this study was a detailed functional interrogation of sequences
      spanning both protective and risk alleles of single nucleotide polymorphism (SNP)
      rs7903146, which has exhibited allele-specific enhancer function in pancreatic
      beta cells. Using these assays, we identified nine segments regulating various
      aspects of the TCF7L2 expression profile and that constitute nearly 70% of the
      sequences tested. These results highlight the regulatory complexity of this
      interval and support the notion that a TCF7L2 cis-regulatory disruption leads to
      T2D predisposition.

PMID- 22590554
TI  - Pretreatment lifestyle behaviors as survival predictors for patients with
      nasopharyngeal carcinoma.
AB  - BACKGROUND: Lifestyle behaviors have been widely reported to influence the
      survival of patients with head and neck cancer. However, the relationship between
      pretreatment lifestyle behaviors and survival among patients with nasopharyngeal
      carcinoma (NPC) is unclear. METHODS: A prospective cohort study was designed to
      determine the relationship between lifestyle behaviors and survival in 1,533 NPC
      patients recruited from October 2005 to October 2007. Pretreatment lifestyle
      behaviors (such as body-mass index [BMI], smoking, alcohol, diet) of the patients
      were investigated. Univariate and multivariate proportional-hazards models were
      used to assess the impact of lifestyle behaviors on patient survival. RESULTS:
      Smoking was a predictor of survival; both current smokers (hazard ratio [HR] =
      1.88; 95% CI, 1.33 to 2.65) and heavy smokers (>= 25 Pack-years; HR = 1.84; 95%
      CI, 1.30 to 2.60) showed associations with poor survival. Higher BMI was
      significantly associated with a lower risk of death (P(trend) = 0.002). Compared
      with under/normal-weight patients (BMI less than 22.99 kg/m(2)), the multivariate
      HR for survival was 0.66 (95% CI, 0.48 to 0.90) and 0.47 (95% CI, 0.23 to 0.97)
      for overweight and obese patients, respectively. No alcohol intake and high fruit
      intake were associated with favorable survival in the univariate analysis but
      lost significance in the multivariate model. CONCLUSION: Our findings indicate
      that pretreatment lifestyle behaviors, especially smoking status and BMI, as
      easily available data, provide prognostic value for survival in NPC patients.

PMID- 22590555
TI  - Pseudomonas syringae pv. actinidiae (PSA) isolates from recent bacterial canker
      of kiwifruit outbreaks belong to the same genetic lineage.
AB  - Intercontinental spread of emerging plant diseases is one of the most serious
      threats to world agriculture. One emerging disease is bacterial canker of kiwi
      fruit (Actinidia deliciosa and A. chinensis) caused by Pseudomonas syringae pv.
      actinidiae (PSA). The disease first occurred in China and Japan in the 1980s and
      in Korea and Italy in the 1990s. A more severe form of the disease broke out in
      Italy in 2008 and in additional countries in 2010 and 2011 threatening the
      viability of the global kiwi fruit industry. To start investigating the source
      and routes of international transmission of PSA, genomes of strains from China
      (the country of origin of the genus Actinidia), Japan, Korea, Italy and Portugal
      have been sequenced. Strains from China, Italy, and Portugal have been found to
      belong to the same clonal lineage with only 6 single nucleotide polymorphisms
      (SNPs) in 3,453,192 bp and one genomic island distinguishing the Chinese strains
      from the European strains. Not more than two SNPs distinguish each of the Italian
      and Portuguese strains from each other. The Japanese and Korean strains belong to
      a separate genetic lineage as previously reported. Analysis of additional
      European isolates and of New Zealand isolates exploiting genome-derived markers
      showed that these strains belong to the same lineage as the Italian and Chinese
      strains. Interestingly, the analyzed New Zealand strains are identical to
      European strains at the tested SNP loci but test positive for the genomic island
      present in the sequenced Chinese strains and negative for the genomic island
      present in the European strains. Results are interpreted in regard to the
      possible direction of movement of the pathogen between countries and suggest a
      possible Chinese origin of the European and New Zealand outbreaks.

PMID- 22590556
TI  - DipA, a pore-forming protein in the outer membrane of Lyme disease spirochetes
      exhibits specificity for the permeation of dicarboxylates.
AB  - Lyme disease Borreliae are highly dependent on the uptake of nutrients provided
      by their hosts. Our study describes the identification of a 36 kDa protein that
      functions as putative dicarboxylate-specific porin in the outer membrane of Lyme
      disease Borrelia. The protein was purified by hydroxyapatite chromatography from
      Borrelia burgdorferi B31 and designated as DipA, for dicarboxylate-specific porin
      A. DipA was partially sequenced, and corresponding genes were identified in the
      genomes of B. burgdorferi B31, Borrelia garinii PBi and Borrelia afzelii PKo.
      DipA exhibits high homology to the Oms38 porins of relapsing fever Borreliae. B.
      burgdorferi DipA was characterized using the black lipid bilayer assay. The
      protein has a single-channel conductance of 50 pS in 1 M KCl, is slightly
      selective for anions with a permeability ratio for cations over anions of 0.57 in
      KCl and is not voltage-dependent. The channel could be partly blocked by
      different di- and tricarboxylic anions. Particular high stability constants up to
      about 28,000 l/mol (in 0.1 M KCl) were obtained among the 11 tested anions for
      oxaloacetate, 2-oxoglutarate and citrate. The results imply that DipA forms a
      porin specific for dicarboxylates which may play an important role for the uptake
      of specific nutrients in different Borrelia species.

PMID- 22590557
TI  - Differential pathogenesis of lung adenocarcinoma subtypes involving sequence
      mutations, copy number, chromosomal instability, and methylation.
AB  - BACKGROUND: Lung adenocarcinoma (LAD) has extreme genetic variation among
      patients, which is currently not well understood, limiting progress in therapy
      development and research. LAD intrinsic molecular subtypes are a validated
      stratification of naturally-occurring gene expression patterns and encompass
      different functional pathways and patient outcomes. Patients may have incurred
      different mutations and alterations that led to the different subtypes. We
      hypothesized that the LAD molecular subtypes co-occur with distinct mutations and
      alterations in patient tumors. METHODOLOGY/PRINCIPAL FINDINGS: The LAD molecular
      subtypes (Bronchioid, Magnoid, and Squamoid) were tested for association with
      gene mutations and DNA copy number alterations using statistical methods and
      published cohorts (n = 504). A novel validation (n = 116) cohort was assayed and
      interrogated to confirm subtype-alteration associations. Gene mutation rates
      (EGFR, KRAS, STK11, TP53), chromosomal instability, regional copy number, and
      genomewide DNA methylation were significantly different among tumors of the
      molecular subtypes. Secondary analyses compared subtypes by integrated
      alterations and patient outcomes. Tumors having integrated alterations in the
      same gene associated with the subtypes, e.g. mutation, deletion and
      underexpression of STK11 with Magnoid, and mutation, amplification, and
      overexpression of EGFR with Bronchioid. The subtypes also associated with tumors
      having concurrent mutant genes, such as KRAS-STK11 with Magnoid. Patient overall
      survival, cisplatin plus vinorelbine therapy response and predicted gefitinib
      sensitivity were significantly different among the subtypes. CONCLUSIONS/
      SIGNIFICANCE: The lung adenocarcinoma intrinsic molecular subtypes co-occur with
      grossly distinct genomic alterations and with patient therapy response. These
      results advance the understanding of lung adenocarcinoma etiology and nominate
      patient subgroups for future evaluation of treatment response.

PMID- 22590558
TI  - A real time Metridia luciferase based non-invasive reporter assay of mammalian
      cell viability and cytotoxicity via the beta-actin promoter and enhancer.
AB  - Secreted reporter molecules offer a means to evaluate biological processes in
      real time without the need to sacrifice samples at pre-determined endpoints. Here
      we have adapted the secreted bioluminescent reporter gene, Metridia luciferase,
      for use in a real-time viability assay for mammalian cells. The coding region of
      the marine copepod gene has been codon optimized for expression in human cells
      (hMLuc) and placed under the control of the human beta-actin promoter and
      enhancer. Metridia luciferase activity of stably transfected cell models
      corresponded linearly with cell number over a 4-log dynamic range, detecting as
      few as 40 cells. When compared to standard endpoint viability assays, which
      measure the mitochondrial dehydrogenase reduction of tetrazolium salts, the hMLuc
      viability assay had a broader linear range of detection, was applicable to large
      tissue culture vessels, and allowed the same sample to be repeatedly measured
      over several days. Additional studies confirmed that MLuc activity was inhibited
      by serum, but demonstrated that assay activity remained linear and was measurable
      in the serum of mice bearing subcutaneous hMLuc-expressing tumors. In summary,
      these comparative studies demonstrate the value of humanized Metridia luciferase
      as an inexpensive and non-invasive method for analyzing viable cell number,
      growth, tumor volume, and therapeutic response in real time.

PMID- 22590559
TI  - Identification of novel single nucleotide polymorphisms (SNPs) in deer
      (Odocoileus spp.) using the BovineSNP50 BeadChip.
AB  - Single nucleotide polymorphisms (SNPs) are growing in popularity as a genetic
      marker for investigating evolutionary processes. A panel of SNPs is often
      developed by comparing large quantities of DNA sequence data across multiple
      individuals to identify polymorphic sites. For non-model species, this is
      particularly difficult, as performing the necessary large-scale genomic
      sequencing often exceeds the resources available for the project. In this study,
      we trial the Bovine SNP50 BeadChip developed in cattle (Bos taurus) for
      identifying polymorphic SNPs in cervids Odocoileus hemionus (mule deer and black
      tailed deer) and O. virginianus (white-tailed deer) in the Pacific Northwest. We
      found that 38.7% of loci could be genotyped, of which 5% (n = 1068) were
      polymorphic. Of these 1068 polymorphic SNPs, a mixture of putatively neutral loci
      (n = 878) and loci under selection (n = 190) were identified with the F(ST)
      outlier method. A range of population genetic analyses were implemented using
      these SNPs and a panel of 10 microsatellite loci. The three types of deer could
      readily be distinguished with both the SNP and microsatellite datasets. This
      study demonstrates that commercially developed SNP chips are a viable means of
      SNP discovery for non-model organisms, even when used between very distantly
      related species (the Bovidae and Cervidae families diverged some 25.1-30.1
      million years before present).

PMID- 22590560
TI  - Ubiquitin-specific protease 25 functions in Endoplasmic Reticulum-associated
      degradation.
AB  - Endoplasmic Reticulum (ER)-associated degradation (ERAD) discards abnormal
      proteins synthesized in the ER. Through coordinated actions of ERAD components,
      misfolded/anomalous proteins are recognized, ubiquitinated, extracted from the ER
      and ultimately delivered to the proteasome for degradation. It is not well
      understood how ubiquitination of ERAD substrates is regulated. Here, we present
      evidence that the deubiquitinating enzyme Ubiquitin-Specific Protease 25 (USP25)
      is involved in ERAD. Our data support a model where USP25 counteracts
      ubiquitination of ERAD substrates by the ubiquitin ligase HRD1, rescuing them
      from degradation by the proteasome.

PMID- 22590561
TI  - Constitutive and treatment-induced CXCL8-signalling selectively modulates the
      efficacy of anti-metabolite therapeutics in metastatic prostate cancer.
AB  - BACKGROUND: The current study was undertaken to characterize the effect of anti
      metabolites on inducing CXCL8 signaling and determining whether the constitutive
      and/or drug-induced CXCL8 signaling in metastatic prostate cancer (CaP) cells
      modulates their sensitivity to this class of agent. METHODS: The response of
      metastatic CaP cells to 5-Fluorouracil (5-FU), Pemetrexed or Tomudex was
      determined using cell count assays, flow cytometry and PARP cleavage analysis.
      Quantitative-PCR, ELISA and immunoblots were employed to determine effects of
      drugs or CXCL8 administration on target gene/protein expression. RESULTS:
      Administration of 5-FU but not pemetrexed potentiated CXCL8 secretion and
      increased CXCR1 and CXCR2 gene expression in metastatic PC3 cells. Consistent
      with this, the inhibition of CXCL8 signaling using a CXCR2 antagonist,
      AZ10397767, increased the cytotoxicity of 5-FU by 4-fold (P<0.001), and increased
      5-FU-induced apoptosis in PC3 cells (P<0.01). In contrast, while administration
      of AZ10397767 had no effect on the sensitivity of pemetrexed, the CXCR2
      antagonist exerted the greatest effect in increasing the sensitivity of PC3 cells
      to Tomudex, a directed thymidylate synthase (TS) inhibitor. Subsequent
      experiments confirmed that administration of recombinant human CXCL8 increased TS
      expression, a response mediated in part by the CXCR2 receptor. Moreover, siRNA
      mediated knockdown of the CXCL8-target gene Bcl-2 increased the sensitivity of
      PC3 cells to 5-FU. CONCLUSIONS: CXCL8 signaling provides a selective resistance
      of metastatic prostate cancer cells to specific anti-metabolites by promoting a
      target-associated resistance, in addition to underpinning an evasion of treatment
      induced apoptosis.

PMID- 22590562
TI  - Integrated analysis of residue coevolution and protein structure in ABC
      transporters.
AB  - Intraprotein side chain contacts can couple the evolutionary process of amino
      acid substitution at one position to that at another. This coupling, known as
      residue coevolution, may vary in strength. Conserved contacts thus not only
      define 3-dimensional protein structure, but also indicate which residue-residue
      interactions are crucial to a protein's function. Therefore, prediction of
      strongly coevolving residue-pairs helps clarify molecular mechanisms underlying
      function. Previously, various coevolution detectors have been employed separately
      to predict these pairs purely from multiple sequence alignments, while
      disregarding available structural information. This study introduces an
      integrative framework that improves the accuracy of such predictions, relative to
      previous approaches, by combining multiple coevolution detectors and
      incorporating structural contact information. This framework is applied to the
      ABC-B and ABC-C transporter families, which include the drug exporter P
      glycoprotein involved in multidrug resistance of cancer cells, as well as the
      CFTR chloride channel linked to cystic fibrosis disease. The predicted coevolving
      pairs are further analyzed based on conformational changes inferred from outward-
      and inward-facing transporter structures. The analysis suggests that some pairs
      coevolved to directly regulate conformational changes of the alternating-access
      transport mechanism, while others to stabilize rigid-body-like components of the
      protein structure. Moreover, some identified pairs correspond to residues
      previously implicated in cystic fibrosis.

PMID- 22590563
TI  - Non-breeding song rate reflects nutritional condition rather than body condition.
AB  - Numerous studies have focused on song in songbirds as a signal involved in mate
      choice and intrasexual competition. It is expected that song traits such as song
      rate reflect individual quality by being dependent on energetic state or
      condition. While seasonal variation in bird song (i.e., breeding versus non
      breeding song) and its neural substrate have received a fair amount of attention,
      the function and information content of song outside the breeding season is
      generally much less understood. Furthermore, typically only measures of condition
      involving body mass are examined with respect to song rate. Studies investigating
      a potential relationship between song rate and other indicators of condition,
      such as physiological measures of nutritional condition, are scant. In this
      study, we examined whether non-breeding song rate in male European starlings
      (Sturnus vulgaris) reflects plasma metabolite levels (high-density lipoproteins
      (HDL), albumin, triglycerides and cholesterol) and/or body mass. Song rate was
      significantly positively related to a principal component representing primarily
      HDL, albumin and cholesterol (and to a lesser degree plasma triglyceride levels).
      There was only a trend toward a significant positive correlation between song
      rate and body mass, and no significant correlation between body mass and the
      abovementioned principal component. Therefore, our results indicate that
      nutritional condition and body mass represent different aspects of condition, and
      that song rate reflects nutritional rather than body condition. Additionally, we
      also found that intra-individual song rate consistency (though not song rate
      itself) was significantly positively related to lutein levels, but not to body
      mass or nutritional condition. Together our results suggest that the relation
      between physiological measures of nutritional condition and song rate, as well as
      other signals, may present an interesting line of future research, both inside
      and outside the breeding season.

PMID- 22590564
TI  - Comparative profiling of Pseudomonas aeruginosa strains reveals differential
      expression of novel unique and conserved small RNAs.
AB  - Pseudomonas aeruginosa is a highly adaptable bacterium that thrives in a broad
      range of ecological niches and can infect multiple hosts as diverse as plants,
      nematodes and mammals. In humans, it is an important opportunistic pathogen. This
      wide adaptability correlates with its broad genetic diversity. In this study, we
      used a deep-sequencing approach to explore the complement of small RNAs (sRNAs)
      in P. aeruginosa as the number of such regulatory molecules previously identified
      in this organism is relatively low, considering its genome size, phenotypic
      diversity and adaptability. We have performed a comparative analysis of PAO1 and
      PA14 strains which share the same host range but differ in virulence, PA14 being
      considerably more virulent in several model organisms. Altogether, we have
      identified more than 150 novel candidate sRNAs and validated a third of them by
      Northern blotting. Interestingly, a number of these novel sRNAs are strain
      specific or showed strain-specific expression, strongly suggesting that they
      could be involved in determining specific phenotypic traits.

PMID- 22590566
TI  - An allograft glioma model reveals the dependence of aquaporin-4 expression on the
      brain microenvironment.
AB  - Aquaporin-4 (AQP4), the main water channel of the brain, is highly expressed in
      animal glioma and human glioblastoma in situ. In contrast, most cultivated glioma
      cell lines don't express AQP4, and primary cell cultures of human glioblastoma
      lose it during the first passages. Accordingly, in C6 cells and RG2 cells, two
      glioma cell lines of the rat, and in SMA mouse glioma cell lines, we found no
      AQP4 expression. We confirmed an AQP4 loss in primary human glioblastoma cell
      cultures after a few passages. RG-2 glioma cells if grafted into the brain
      developed AQP4 expression. This led us consider the possibility of AQP4
      expression depends on brain microenvironment. In previous studies, we observed
      that the typical morphological conformation of AQP4 as orthogonal arrays of
      particles (OAP) depended on the extracellular matrix component agrin. In this
      study, we showed for the first time implanted AQP4 negative glioma cells in
      animal brain or flank to express AQP4 specifically in the intracerebral gliomas
      but neither in the extracranial nor in the flank gliomas. AQP4 expression in
      intracerebral gliomas went along with an OAP loss, compared to normal brain
      tissue. AQP4 staining in vivo normally is polarized in the astrocytic endfoot
      membranes at the glia limitans superficialis and perivascularis, but in C6 and
      RG2 tumors the AQP4 staining is redistributed over the whole glioma cell as in
      human glioblastoma. In contrast, primary rat or mouse astrocytes in culture did
      not lose their ability to express AQP4, and they were able to form few OAPs.

PMID- 22590567
TI  - Regulation of neuronal cell death by c-Abl-Hippo/MST2 signaling pathway.
AB  - BACKGROUND: Mammalian Ste20-like kinases (MSTs) are the mammalian homologue of
      Drosophila hippo and play critical roles in regulation of cell death, organ size
      control, proliferation and tumorigenesis. MSTs exert pro-apoptotic function
      through cleavage, autophosphorylation and in turn phosphorylation of downstream
      targets, such as Histone H2B and FOXO (Forkhead box O). Previously we reported
      that protein kinase c-Abl mediates oxidative stress-induced neuronal cell death
      through phosphorylating MST1 at Y433, which is not conserved among mammalian
      MST2, Drosophila Hippo and C.elegans cst-1/2. METHODOLOGY/PRINCIPAL FINDINGS:
      Using immunoblotting, in vitro kinase and cell death assay, we demonstrate that c
      Abl kinase phosphorylates MST2 at an evolutionarily conserved site, Y81, within
      the kinase domain. We further show that the phosphorylation of MST2 by c-Abl
      leads to the disruption of the interaction with Raf-1 proteins and the
      enhancement of homodimerization of MST2 proteins. It thereby enhances the MST2
      activation and induces neuronal cell death. CONCLUSIONS/SIGNIFICANCE: The
      identification of the c-Abl tyrosine kinase as a novel upstream activator of MST2
      suggests that the conserved c-Abl-MST signaling cascade plays an important role
      in oxidative stress-induced neuronal cell death.

PMID- 22590568
TI  - Consistency of leadership in shoals of mosquitofish (Gambusia holbrooki) in novel
      and in familiar environments.
AB  - In social animal groups, an individual's spatial position is a major determinant
      of both predation risk and foraging rewards. Additionally, the occupation of
      positions in the front of moving groups is generally assumed to correlate with
      the initiation of group movements. However, whether some individuals are
      predisposed to consistently occupy certain positions and, in some instances, to
      consistently lead groups over time is as yet unresolved in many species. Using
      the mosquitofish (Gambusia holbrooki), we examined the consistency of
      individuals' spatial positions within a moving group over successive trials. We
      found that certain individuals consistently occupied front positions in moving
      groups and also that it was typically these individuals that initiated group
      decisions. The number of individuals involved in leading the group varied
      according to the amount of information held by group members, with a greater
      number of changes in leadership in a novel compared to a relatively familiar
      environment. Finally, our results show that the occupation of lead positions in
      moving groups was not explained by characteristics such as dominance, size or
      sex, suggesting that certain individuals are predisposed to leadership roles.
      This suggests that being a leader or a follower may to some extent be an
      intrinsic property of the individual.

PMID- 22590565
TI  - Sequencing and analysis of the Mediterranean amphioxus (Branchiostoma
      lanceolatum) transcriptome.
AB  - BACKGROUND: The basally divergent phylogenetic position of amphioxus
      (Cephalochordata), as well as its conserved morphology, development and genetics,
      make it the best proxy for the chordate ancestor. Particularly, studies using the
      amphioxus model help our understanding of vertebrate evolution and development.
      Thus, interest for the amphioxus model led to the characterization of both the
      transcriptome and complete genome sequence of the American species, Branchiostoma
      floridae. However, recent technical improvements allowing induction of spawning
      in the laboratory during the breeding season on a daily basis with the
      Mediterranean species Branchiostoma lanceolatum have encouraged European Evo-Devo
      researchers to adopt this species as a model even though no genomic or
      transcriptomic data have been available. To fill this need we used the
      pyrosequencing method to characterize the B. lanceolatum transcriptome and then
      compared our results with the published transcriptome of B. floridae. RESULTS:
      Starting with total RNA from nine different developmental stages of B.
      lanceolatum, a normalized cDNA library was constructed and sequenced on Roche GS
      FLX (Titanium mode). Around 1.4 million of reads were produced and assembled into
      70,530 contigs (average length of 490 bp). Overall 37% of the assembled sequences
      were annotated by BlastX and their Gene Ontology terms were determined. These
      results were then compared to genomic and transcriptomic data of B. floridae to
      assess similarities and specificities of each species. CONCLUSION: We obtained a
      high-quality amphioxus (B. lanceolatum) reference transcriptome using a high
      throughput sequencing approach. We found that 83% of the predicted genes in the
      B. floridae complete genome sequence are also found in the B. lanceolatum
      transcriptome, while only 41% were found in the B. floridae transcriptome
      obtained with traditional Sanger based sequencing. Therefore, given the high
      degree of sequence conservation between different amphioxus species, this set of
      ESTs may now be used as the reference transcriptome for the Branchiostoma genus.

PMID- 22590569
TI  - Detection of retroviral super-infection from non-invasive samples.
AB  - While much attention has been focused on the molecular epidemiology of
      retroviruses in wild primate populations, the correlated question of the
      frequency and nature of super-infection events, i.e., the simultaneous infection
      of the same individual host with several strains of the same virus, has remained
      largely neglected. In particular, methods possibly allowing the investigation of
      super-infection from samples collected non-invasively (such as faeces) have never
      been properly compared. Here, we fill in this gap by assessing the costs and
      benefits of end-point dilution PCR (EPD-PCR) and multiple bulk-PCR cloning, as
      applied to a case study focusing on simian foamy virus super-infection in wild
      chimpanzees (Pan troglodytes). We show that, although considered to be the gold
      standard, EPD-PCR can lead to massive consumption of biological material when
      only low copy numbers of the target are expected. This constitutes a serious
      drawback in a field in which rarity of biological material is a fundamental
      constraint. In addition, we demonstrate that EPD-PCR results (single/multiple
      infection; founder strains) can be well predicted from multiple bulk-PCR clone
      experiments, by applying simple statistical and network analyses to sequence
      alignments. We therefore recommend the implementation of the latter method when
      the focus is put on retroviral super-infection and only low retroviral loads are
      encountered.

PMID- 22590570
TI  - Phylogenetic analysis of Bolivian bat trypanosomes of the subgenus schizotrypanum
      based on cytochrome B sequence and minicircle analyses.
AB  - The aim of this study was to establish the phylogenetic relationships of
      trypanosomes present in blood samples of Bolivian Carollia bats. Eighteen cloned
      stocks were isolated from 115 bats belonging to Carollia perspicillata
      (Phyllostomidae) from three Amazonian areas of the Chapare Province of Bolivia
      and studied by xenodiagnosis using the vectors Rhodnius robustus and Triatoma
      infestans (Trypanosoma cruzi marenkellei) or haemoculture (Trypanosoma dionisii).
      The PCR DNA amplified was analyzed by nucleotide sequences of maxicircles
      encoding cytochrome b and by means of the molecular size of hyper variable
      regions of minicircles. Ten samples were classified as Trypanosoma cruzi
      marinkellei and 8 samples as Trypanosoma dionisii. The two species have a
      different molecular size profile with respect to the amplified regions of
      minicircles and also with respect to Trypanosoma cruzi and Trypanosoma rangeli
      used for comparative purpose. We conclude the presence of two species of bat
      trypanosomes in these samples, which can clearly be identified by the methods
      used in this study. The presence of these trypanosomes in Amazonian bats is
      discussed.

PMID- 22590571
TI  - Knotty-centrality: finding the connective core of a complex network.
AB  - A network measure called knotty-centrality is defined that quantifies the extent
      to which a given subset of a graph's nodes constitutes a densely intra-connected
      topologically central connective core. Using this measure, the knotty centre of a
      network is defined as a sub-graph with maximal knotty-centrality. A heuristic
      algorithm for finding subsets of a network with high knotty-centrality is
      presented, and this is applied to previously published brain structural
      connectivity data for the cat and the human, as well as to a number of other
      networks. The cognitive implications of possessing a connective core with high
      knotty-centrality are briefly discussed.

PMID- 22590572
TI  - C. elegans EIF-3.K promotes programmed cell death through CED-3 caspase.
AB  - Programmed cell death (apoptosis) is essential for the development and
      homeostasis of metazoans. The central step in the execution of programmed cell
      death is the activation of caspases. In C. elegans, the core cell death
      regulators EGL-1(a BH3 domain-containing protein), CED-9 (Bcl-2), and CED-4 (Apaf
      1) act in an inhibitory cascade to activate the CED-3 caspase. Here we have
      identified an additional component eif-3.K (eukaryotic translation initiation
      factor 3 subunit k) that acts upstream of ced-3 to promote programmed cell death.
      The loss of eif-3.K reduced cell deaths in both somatic and germ cells, whereas
      the overexpression of eif-3.K resulted in a slight but significant increase in
      cell death. Using a cell-specific promoter, we show that eif-3.K promotes cell
      death in a cell-autonomous manner. In addition, the loss of eif-3.K significantly
      suppressed cell death-induced through the overexpression of ced-4, but not ced-3,
      indicating a distinct requirement for eif-3.K in apoptosis. Reciprocally, a loss
      of ced-3 suppressed cell death induced by the overexpression of eif-3.K. These
      results indicate that eif-3.K requires ced-3 to promote programmed cell death and
      that eif-3.K acts upstream of ced-3 to promote this process. The EIF-3.K protein
      is ubiquitously expressed in embryos and larvae and localizes to the cytoplasm. A
      structure-function analysis revealed that the 61 amino acid long WH domain of EIF
      3.K, potentially involved in protein-DNA/RNA interactions, is both necessary and
      sufficient for the cell death-promoting activity of EIF-3.K. Because human eIF3k
      was able to partially substitute for C. elegans eif-3.K in the promotion of cell
      death, this WH domain-dependent EIF-3.K-mediated cell death process has
      potentially been conserved throughout evolution.

PMID- 22590573
TI  - Kaposi's sarcoma associated herpesvirus encoded viral FLICE inhibitory protein
      K13 activates NF-kappaB pathway independent of TRAF6, TAK1 and LUBAC.
AB  - BACKGROUND: Kaposi's sarcoma associated herpesvirus encoded viral FLICE
      inhibitory protein (vFLIP) K13 activates the NF-kappaB pathway by binding to the
      NEMO/IKKgamma subunit of the IkappaB kinase (IKK) complex. However, it has
      remained enigmatic how K13-NEMO interaction results in the activation of the IKK
      complex. Recent studies have implicated TRAF6, TAK1 and linear ubiquitin chains
      assembled by a linear ubiquitin chain assembly complex (LUBAC) consisting of HOIL
      1, HOIP and SHARPIN in IKK activation by proinflammatory cytokines.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that K13-induced NF-kappaB
      DNA binding and transcriptional activities are not impaired in cells derived from
      mice with targeted disruption of TRAF6, TAK1 and HOIL-1 genes and in cells
      derived from mice with chronic proliferative dermatitis (cpdm), which have
      mutation in the Sharpin gene (Sharpin(cpdm/cpdm)). Furthermore, reconstitution of
      NEMO-deficient murine embryonic fibroblast cells with NEMO mutants that are
      incapable of binding to linear ubiquitin chains supported K13-induced NF-kappaB
      activity. K13-induced NF-kappaB activity was not blocked by CYLD, a
      deubiquitylating enzyme that can cleave linear and Lys63-linked ubiquitin chains.
      On the other hand, NEMO was required for interaction of K13 with IKK1/IKKalpha
      and IKK2/IKKbeta, which resulted in their activation by "T Loop" phosphorylation.
      CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that K13 activates the NF
      kappaB pathway by binding to NEMO which results in the recruitment of
      IKK1/IKKalpha and IKK2/IKKbeta and their subsequent activation by
      phosphorylation. Thus, K13 activates NF-kappaB via a mechanism distinct from that
      utilized by inflammatory cytokines. These results have important implications for
      the development of therapeutic agents targeting K13-induced NF-kappaB for the
      treatment of KSHV-associated malignancies.

PMID- 22590574
TI  - Late onset myasthenia gravis is associated with HLA DRB1*15:01 in the Norwegian
      population.
AB  - BACKGROUND: Acquired myasthenia gravis (MG) is a rare antibody-mediated
      autoimmune disease caused by impaired neuromuscular transmission, leading to
      abnormal muscle fatigability. The aetiology is complex, including genetic risk
      factors of the human leukocyte antigen (HLA) complex and unknown environmental
      factors. Although associations between the HLA complex and MG are well
      established, not all involved components of the HLA predisposition to this
      heterogeneous disease have been revealed. Well-powered and comprehensive HLA
      analyses of subgroups in MG are warranted, especially in late onset MG.
      METHODOLOGY/PRINCIPAL FINDINGS: This case-control association study is of a large
      population-based Norwegian cohort of 369 MG patients and 651 healthy controls. We
      performed comprehensive genotyping of four classical HLA loci (HLA-A, -B, -C and 
      DRB1) and showed that the DRB1*15:01 allele conferred the strongest risk in late
      onset MG (LOMG; onset >= 60 years) (OR 2.38, p(c)7.4 * 10(-5)). DRB1*13:01 was
      found to be a protective allele for both early onset MG (EOMG) and LOMG (OR 0.31,
      p(c) 4.71 * 10(-4)), a finding not previously described. No significant
      association was found to the DRB1*07:01 allele (p(nc) = 0.18) in a subset of
      nonthymomatous anti-titin antibody positive LOMG as reported by others. HLA-B*08
      was mapped to give the strongest contribution to EOMG, supporting previous
      studies. CONCLUSION: The results from this study provide important new
      information concerning the susceptibility of HLA alleles in Caucasian MG, with
      highlights on DRB1*15:01 as being a major risk allele in LOMG.

PMID- 22590575
TI  - Base-pairing versatility determines wobble sites in tRNA anticodons of vertebrate
      mitogenomes.
AB  - BACKGROUND: Vertebrate mitochondrial genomes typically have one transfer RNA
      (tRNA) for each synonymous codon family. This limited anticodon repertoire
      implies that each tRNA anticodon needs to wobble (establish a non-Watson-Crick
      base pairing between two nucleotides in RNA molecules) to recognize one or more
      synonymous codons. Different hypotheses have been proposed to explain the factors
      that determine the nucleotide composition of wobble sites in vertebrate
      mitochondrial tRNA anticodons. Until now, the two major postulates--the "codon
      anticodon adaptation hypothesis" and the "wobble versatility hypothesis"--have
      not been formally tested in vertebrate mitochondria because both make the same
      predictions regarding the composition of anticodon wobble sites. The same is true
      for the more recent "wobble cost hypothesis". PRINCIPAL FINDINGS: In this study
      we have analyzed the occurrence of synonymous codons and tRNA anticodon wobble
      sites in 1553 complete vertebrate mitochondrial genomes, focusing on three fish
      species with mtDNA codon usage bias reversal (L-strand is GT-rich). These
      mitogenomes constitute an excellent opportunity to study the evolution of the
      wobble nucleotide composition of tRNA anticodons because due to the reversal the
      predictions for the anticodon wobble sites differ between the existing
      hypotheses. We observed that none of the wobble sites of tRNA anticodons in these
      unusual mitochondrial genomes coevolved to match the new overall codon usage
      bias, suggesting that nucleotides at the wobble sites of tRNA anticodons in
      vertebrate mitochondrial genomes are determined by wobble versatility.
      CONCLUSIONS/SIGNIFICANCE: Our results suggest that, at wobble sites of tRNA
      anticodons in vertebrate mitogenomes, selection favors the most versatile
      nucleotide in terms of wobble base-pairing stability and that wobble site
      composition is not influenced by codon usage. These results are in agreement with
      the "wobble versatility hypothesis".

PMID- 22590576
TI  - Population genetic structure and colonisation history of the tool-using New
      Caledonian crow.
AB  - New Caledonian crows exhibit considerable variation in tool making between
      populations. Here, we present the first study of the species' genetic structure
      over its geographical distribution. We collected feathers from crows on mainland
      Grande Terre, the inshore island of Toupeti, and the nearby island of Mare where
      it is believed birds were introduced after European colonisation. We used nine
      microsatellite markers to establish the genotypes of 136 crows from these islands
      and classical population genetic tools as well as Approximate Bayesian
      Computations to explore the distribution of genetic diversity. We found that New
      Caledonian crows most likely separate into three main distinct clusters: Grande
      Terre, Toupeti and Mare. Furthermore, Toupeti and Mare crows represent a subset
      of the genetic diversity observed on Grande Terre, confirming their mainland
      origin. The genetic data are compatible with a colonisation of Mare taking place
      after European colonisation around 1900. Importantly, we observed (1) moderate,
      but significant, genetic differentiation across Grande Terre, and (2) that the
      degree of differentiation between populations on the mainland increases with
      geographic distance. These data indicate that despite individual crows' potential
      ability to disperse over large distances, most gene flow occurs over short
      distances. The temporal and spatial patterns described provide a basis for
      further hypothesis testing and investigation of the geographical variation
      observed in the tool skills of these crows.

PMID- 22590577
TI  - In silico assessment of potential druggable pockets on the surface of alpha1
      antitrypsin conformers.
AB  - The search for druggable pockets on the surface of a protein is often performed
      on a single conformer, treated as a rigid body. Transient druggable pockets may
      be missed in this approach. Here, we describe a methodology for systematic in
      silico analysis of surface clefts across multiple conformers of the metastable
      protein alpha(1)-antitrypsin (A1AT). Pathological mutations disturb the
      conformational landscape of A1AT, triggering polymerisation that leads to
      emphysema and hepatic cirrhosis. Computational screens for small molecule
      inhibitors of polymerisation have generally focused on one major druggable site
      visible in all crystal structures of native A1AT. In an alternative approach, we
      scan all surface clefts observed in crystal structures of A1AT and in 100
      computationally produced conformers, mimicking the native solution ensemble. We
      assess the persistence, variability and druggability of these pockets. Finally,
      we employ molecular docking using publicly available libraries of small molecules
      to explore scaffold preferences for each site. Our approach identifies a number
      of novel target sites for drug design. In particular one transient site shows
      favourable characteristics for druggability due to high enclosure and
      hydrophobicity. Hits against this and other druggable sites achieve docking
      scores corresponding to a K(d) in the uM-nM range, comparing favourably with a
      recently identified promising lead. Preliminary ThermoFluor studies support the
      docking predictions. In conclusion, our strategy shows considerable promise
      compared with the conventional single pocket/single conformer approach to in
      silico screening. Our best-scoring ligands warrant further experimental
      investigation.

PMID- 22590578
TI  - Propiconazole is a specific and accessible brassinosteroid (BR) biosynthesis
      inhibitor for Arabidopsis and maize.
AB  - Brassinosteroids (BRs) are steroidal hormones that play pivotal roles during
      plant development. In addition to the characterization of BR deficient mutants,
      specific BR biosynthesis inhibitors played an essential role in the elucidation
      of BR function in plants. However, high costs and limited availability of common
      BR biosynthetic inhibitors constrain their key advantage as a species-independent
      tool to investigate BR function. We studied propiconazole (Pcz) as an alternative
      to the BR inhibitor brassinazole (Brz). Arabidopsis seedlings treated with Pcz
      phenocopied BR biosynthetic mutants. The steady state mRNA levels of BR, but not
      gibberellic acid (GA), regulated genes increased proportional to the
      concentrations of Pcz. Moreover, root inhibition and Pcz-induced expression of BR
      biosynthetic genes were rescued by 24epi-brassinolide, but not by GA(3) co
      applications. Maize seedlings treated with Pcz showed impaired mesocotyl,
      coleoptile, and true leaf elongation. Interestingly, the genetic background
      strongly impacted the tissue specific sensitivity towards Pcz. Based on these
      findings we conclude that Pcz is a potent and specific inhibitor of BR
      biosynthesis and an alternative to Brz. The reduced cost and increased
      availability of Pcz, compared to Brz, opens new possibilities to study BR
      function in larger crop species.

PMID- 22590579
TI  - Promising system for selecting healthy in vitro-fertilized embryos in cattle.
AB  - Conventionally, in vitro-fertilized (IVF) bovine embryos are morphologically
      evaluated at the time of embryo transfer to select those that are likely to
      establish a pregnancy. This method is, however, subjective and results in
      unreliable selection. Here we describe a novel selection system for IVF bovine
      blastocysts for transfer that traces the development of individual embryos with
      time-lapse cinematography in our developed microwell culture dish and analyzes
      embryonic metabolism. The system can noninvasively identify prognostic factors
      that reflect not only blastocyst qualities detected with histological,
      cytogenetic, and molecular analysis but also viability after transfer. By
      assessing a combination of identified prognostic factors--(i) timing of the first
      cleavage; (ii) number of blastomeres at the end of the first cleavage; (iii)
      presence or absence of multiple fragments at the end of the first cleavage; (iv)
      number of blastomeres at the onset of lag-phase, which results in temporary
      developmental arrest during the fourth or fifth cell cycle; and (v) oxygen
      consumption at the blastocyst stage--pregnancy success could be accurately
      predicted (78.9%). The conventional method or individual prognostic factors could
      not accurately predict pregnancy. No newborn calves showed neonatal overgrowth or
      death. Our results demonstrate that these five predictors and our system could
      provide objective and reliable selection of healthy IVF bovine embryos.

PMID- 22590580
TI  - Pharmacogenetics meets metabolomics: discovery of tryptophan as a new endogenous
      OCT2 substrate related to metformin disposition.
AB  - Genetic polymorphisms of the organic cation transporter 2 (OCT2), encoded by
      SLC22A2, have been investigated in association with metformin disposition. A
      functional decrease in transport function has been shown to be associated with
      the OCT2 variants. Using metabolomics, our study aims at a comprehensive
      monitoring of primary metabolite changes in order to understand biochemical
      alteration associated with OCT2 polymorphisms and discovery of potential
      endogenous metabolites related to the genetic variation of OCT2. Using GC-TOF MS
      based metabolite profiling, clear clustering of samples was observed in Partial
      Least Square Discriminant Analysis, showing that metabolic profiles were linked
      to the genetic variants of OCT2. Tryptophan and uridine presented the most
      significant alteration in SLC22A2-808TT homozygous and the SLC22A2-808G>T
      heterozygous variants relative to the reference. Particularly tryptophan showed
      gene-dose effects of transporter activity according to OCT2 genotypes and the
      greatest linear association with the pharmacokinetic parameters (Cl(renal),
      Cl(sec), Cl/F/kg, and Vd/F/kg) of metformin. An inhibition assay demonstrated the
      inhibitory effect of tryptophan on the uptake of 1-methyl-4-phenyl pyrinidium in
      a concentration dependent manner and subsequent uptake experiment revealed
      differential tryptophan-uptake rate in the oocytes expressing OCT2 reference and
      variant (808G>T). Our results collectively indicate tryptophan can serve as one
      of the endogenous substrate for the OCT2 as well as a biomarker candidate
      indicating the variability of the transport activity of OCT2.

PMID- 22590581
TI  - Environmental and genetic effects on pigment-based vs. structural component of
      yellow feather colouration.
AB  - BACKGROUND: Carotenoid plumage is of widespread use in bird communication.
      Carotenoid-based feather colouration has recently been shown to be dependent on
      both pigment concentration and feather structure. If these two components are
      determined differently, one plumage patch may potentially convey different
      aspects of individual quality. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the
      effects of genetic and environmental factors on carotenoid-based yellow breast
      colouration of Great Tit (Parus major) nestlings. By partial cross-fostering, we
      separated the genetic and pre-natal vs. post-natal parental effects on both the
      structural and the pigment-based component of carotenoid-based plumage
      colouration. We also simultaneously manipulated the post-hatching environment by
      brood size manipulation. The structural component of nestling colouration
      reflected features of female colouration. On the other hand, the pigment-based
      component was more affected by rearing conditions presumably representing food
      quality. While the structural component was related to both origin- and
      environment-related factors, the pigment-based component seemed to be environment
      dependent only. These results support the notion that pigment-based and
      structural components of feather colouration are determined differently.
      CONCLUSIONS/SIGNIFICANCE: Chromatic and achromatic components of carotenoid-based
      feather colouration reflected different aspects of individual quality and
      history, and thus may potentially form a multicomponent signal.

PMID- 22590582
TI  - Grooming up the hierarchy: the exchange of grooming and rank-related benefits in
      a new world primate.
AB  - Seyfarth's model assumes that female primates derive rank-related benefits from
      higher-ranking females in exchange for grooming. As a consequence, the model
      predicts females prefer high-ranking females as grooming partners and compete for
      the opportunity to groom them. Therefore, allogrooming is expected to be directed
      up the dominance hierarchy and to occur more often between females with adjacent
      ranks. Although data from Old World primates generally support the model, studies
      on the relation between grooming and dominance rank in the New World genus Cebus
      have found conflicting results, showing considerable variability across groups
      and species. In this study, we investigated the pattern of grooming in wild
      tufted capuchin females (Cebus apella nigritus) in Iguazu National Park,
      Argentina by testing both the assumption (i.e., that females gain rank-related
      return benefits from grooming) and predictions (i.e., that females direct
      grooming up the dominance hierarchy and the majority of grooming occurs between
      females with adjacent ranks) of Seyfarth's model. Study subjects were 9 adult
      females belonging to a single group. Results showed that grooming was given in
      return for tolerance during naturally occurring feeding, a benefit that higher
      ranking females can more easily grant. Female grooming was directed up the
      hierarchy and was given more often to partners with similar rank. These findings
      provide supporting evidence for both the assumption and predictions of Seyfarth's
      model and represent, more generally, the first evidence of reciprocal behavioural
      interchanges driven by rank-related benefits in New World female primates.

PMID- 22590583
TI  - Anti-HPV16 E2 protein T-cell responses and viral control in women with usual
      vulvar intraepithelial neoplasia and their healthy partners.
AB  - T-cell responses (proliferation, intracellular cytokine synthesis and IFNgamma
      ELISPOT) against human papillomavirus 16 (HPV16) E2 peptides were tested during
      18 months in a longitudinal study in eight women presenting with HPV16-related
      usual vulvar intraepithelial neoplasia (VIN) and their healthy male partners. In
      six women, anti-E2 proliferative responses and cytokine production (single
      IFNgamma and/or dual IFNgamma/IL2 and/or single IL2) by CD4+ T lymphocytes became
      detectable after treating and healing of the usual VIN. In the women presenting
      with persistent lesions despite therapy, no proliferation was observed. Anti-E2
      proliferative responses were also observed with dual IFNgamma/IL2 production by
      CD4+ T-cells in six male partners who did not exhibit any genital HPV-related
      diseases. Ex vivo IFNgamma ELISPOT showed numerous effector T-cells producing
      IFNgamma after stimulation by a dominant E2 peptide in all men and women. Since
      the E2 protein is absent from the viral particles but is required for viral DNA
      replication, these results suggest a recent infection with replicative HPV16 in
      male partners. The presence of polyfunctional anti-E2 T-cell responses in the
      blood of asymptomatic men unambiguously establishes HPV infection even without
      detectable lesions. These results, despite the small size of the studied group,
      provide an argument in favor of prophylactic HPV vaccination of young men in
      order to prevent HPV16 infection and viral transmission from men to women.

PMID- 22590584
TI  - Development of transgenic cloned pig models of skin inflammation by DNA
      transposon-directed ectopic expression of human beta1 and alpha2 integrin.
AB  - Integrins constitute a superfamily of transmembrane signaling receptors that play
      pivotal roles in cutaneous homeostasis by modulating cell growth and
      differentiation as well as inflammatory responses in the skin. Subrabasal
      expression of integrins alpha2 and/or beta1 entails hyperproliferation and
      aberrant differentiation of keratinocytes and leads to dermal and epidermal
      influx of activated T-cells. The anatomical and physiological similarities
      between porcine and human skin make the pig a suitable model for human skin
      diseases. In efforts to generate a porcine model of cutaneous inflammation, we
      employed the Sleeping Beauty DNA transposon system for production of transgenic
      cloned Gottingen minipigs expressing human beta1 or alpha2 integrin under the
      control of a promoter specific for subrabasal keratinocytes. Using pools of
      transgenic donor fibroblasts, cloning by somatic cell nuclear transfer was
      utilized to produce reconstructed embryos that were subsequently transferred to
      surrogate sows. The resulting pigs were all transgenic and harbored from one to
      six transgene integrants. Molecular analyses on skin biopsies and cultured
      keratinocytes showed ectopic expression of the human integrins and localization
      within the keratinocyte plasma membrane. Markers of perturbed skin homeostasis,
      including activation of the MAPK pathway, increased expression of the pro
      inflammatory cytokine IL-1alpha, and enhanced expression of the transcription
      factor c-Fos, were identified in keratinocytes from beta1 and alpha2 integrin
      transgenic minipigs, suggesting the induction of a chronic inflammatory phenotype
      in the skin. Notably, cellular dysregulation obtained by overexpression of either
      beta1 or alpha2 integrin occurred through different cellular signaling pathways.
      Our findings mark the creation of the first cloned pig models with molecular
      markers of skin inflammation. Despite the absence of an overt psoriatic
      phenotype, these animals may possess increased susceptibility to severe skin
      damage-induced inflammation and should be of great potential in studies aiming at
      the development and refinement of topical therapies for cutaneous inflammation
      including psoriasis.

PMID- 22590585
TI  - MSMEG_2731, an uncharacterized nucleic acid binding protein from Mycobacterium
      smegmatis, physically interacts with RPS1.
AB  - While the M. smegmatis genome has been sequenced, only a small portion of the
      genes have been characterized experimentally. Here, we purify and characterize
      MSMEG_2731, a conserved hypothetical alanine and arginine rich M. smegmatis
      protein. Using ultracentrifugation, we show that MSMEG_2731 is a monomer in
      vitro. MSMEG_2731 exists at a steady level throughout the M. smegmatis life
      cycle. Combining results from pull-down techniques and LS-MS/MS, we show that
      MSMEG_2731 interacts with ribosomal protein S1. The existence of this interaction
      was confirmed by co-immunoprecipitation. We also show that MSMEG_2731 can bind
      ssDNA, dsDNA and RNA in vitro. Based on the interactions of MSMEG_2731 with RPS1
      and RNA, we propose that MSMEG_2731 is involved in the transcription-translation
      process in vivo.

PMID- 22590586
TI  - Loss of the urothelial differentiation marker FOXA1 is associated with high
      grade, late stage bladder cancer and increased tumor proliferation.
AB  - Approximately 50% of patients with muscle-invasive bladder cancer (MIBC) develop
      metastatic disease, which is almost invariably lethal. However, our understanding
      of pathways that drive aggressive behavior of MIBC is incomplete. Members of the
      FOXA subfamily of transcription factors are implicated in normal urogenital
      development and urologic malignancies. FOXA proteins are implicated in normal
      urothelial differentiation, but their role in bladder cancer is unknown. We
      examined FOXA expression in commonly used in vitro models of bladder cancer and
      in human bladder cancer specimens, and used a novel in vivo tissue recombination
      system to determine the functional significance of FOXA1 expression in bladder
      cancer. Logistic regression analysis showed decreased FOXA1 expression is
      associated with increasing tumor stage (p<0.001), and loss of FOXA1 is associated
      with high histologic grade (p<0.001). Also, we found that bladder urothelium that
      has undergone keratinizing squamous metaplasia, a precursor to the development of
      squamous cell carcinoma (SCC) exhibited loss of FOXA1 expression. Furthermore,
      81% of cases of SCC of the bladder were negative for FOXA1 staining compared to
      only 40% of urothelial cell carcinomas. In addition, we showed that a
      subpopulation of FOXA1 negative urothelial tumor cells are highly proliferative.
      Knockdown of FOXA1 in RT4 bladder cancer cells resulted in increased expression
      of UPK1B, UPK2, UPK3A, and UPK3B, decreased E-cadherin expression and
      significantly increased cell proliferation, while overexpression of FOXA1 in T24
      cells increased E-cadherin expression and significantly decreased cell growth and
      invasion. In vivo recombination of bladder cancer cells engineered to exhibit
      reduced FOXA1 expression with embryonic rat bladder mesenchyme and subsequent
      renal capsule engraftment resulted in enhanced tumor proliferation. These
      findings provide the first evidence linking loss of FOXA1 expression with
      histological subtypes of MIBC and urothelial cell proliferation, and suggest an
      important role for FOXA1 in the malignant phenotype of MIBC.

PMID- 22590587
TI  - Associations between nitric oxide synthase genes and exhaled NO-related
      phenotypes according to asthma status.
AB  - BACKGROUND: The nitric oxide (NO) pathway is involved in asthma, and eosinophils
      participate in the regulation of the NO pool in pulmonary tissues. We
      investigated associations between single nucleotide polymorphisms (SNPs) of NO
      synthase genes (NOS) and biological NO-related phenotypes measured in two
      compartments (exhaled breath condensate and plasma) and blood eosinophil counts.
      METHODOLOGY: SNPs (N = 121) belonging to NOS1, NOS2 and NOS3 genes were genotyped
      in 1277 adults from the French Epidemiological study on the Genetics and
      Environment of Asthma (EGEA). Association analyses were conducted on four
      quantitative phenotypes: the exhaled fraction of NO (Fe(NO)), plasma and exhaled
      breath condensate (EBC) nitrite-nitrate levels (NO2-NO3) and blood eosinophils in
      asthmatics and non-asthmatics separately. Genetic heterogeneity of these
      phenotypes between asthmatics and non-asthmatics was also investigated. PRINCIPAL
      FINDINGS: In non-asthmatics, after correction for multiple comparisons, we found
      significant associations of Fe(NO) levels with three SNPs in NOS3 and NOS2 (P <=
      0.002), and of EBC NO2-NO3 level with NOS2 (P = 0.002). In asthmatics, a single
      significant association was detected between Fe(NO) levels and one SNP in NOS3 (P
      = 0.004). Moreover, there was significant heterogeneity of NOS3 SNP effect on
      Fe(NO) between asthmatics and non-asthmatics (P = 0.0002 to 0.005). No
      significant association was found between any SNP and NO2-NO3 plasma levels or
      blood eosinophil counts. CONCLUSIONS: Variants in NO synthase genes influence
      Fe(NO) and EBC NO2-NO3 levels in adults. These genetic determinants differ
      according to asthma status. Significant associations were only detected for
      exhaled phenotypes, highlighting the critical relevance to have access to
      specific phenotypes measured in relevant biological fluid.

PMID- 22590588
TI  - Impact of low-level-viremia on HIV-1 drug-resistance evolution among
      antiretroviral treated-patients.
AB  - BACKGROUND: Drug-resistance mutations (DRAM) are frequently selected in patients
      with virological failure defined as viral load (pVL) above 500 copies/ml (c/mL),
      but few resistance data are available at low-level viremia (LLV). Our objective
      was to determine the emergence and evolution of DRAM during LLV in HIV-1-infected
      patients while receiving antiretroviral therapy (ART). METHODS: Retrospective
      analysis of patients presenting a LLV episode defined as pVL between 40 and 500
      c/mL on at least 3 occasions during a 6-month period or longer while on the same
      ART. Resistance genotypic testing was performed at the onset and at the end of
      LLV period. Emerging DRAM was defined during LLV if never detected on baseline
      genotype or before. RESULTS: 48 patients including 4 naive and 44 pretreated
      (median 9 years) presented a LLV episode with a median duration of 11 months.
      Current ART included 2NRTI (94%), ritonavir-boosted PI (94%), NNRTI (23%), and/or
      raltegravir (19%). Median pVL during LLV was 134 c/mL. Successful resistance
      testing at both onset and end of the LLV episode were obtained for 37 patients
      (77%), among who 11 (30%) acquired at least 1 DRAM during the LLV period: for
      NRTI in 6, for NNRTI in 1, for PI in 4, and for raltegravir in 2. During the LLV
      period, number of drugs with genotypic resistance increased from a median of 4.5
      to 6 drugs. Duration and pVL level of LLV episode, duration of previous ART,
      current and nadir CD4 count, number of baseline DRAM and GSS were not identified
      as predictive factors of resistance acquisition during LLV, probably due to
      limited number of patients. CONCLUSION: Persistent LLV episodes below 500 c/ml
      while receiving ART is associated with emerging DRAM for all drug classes and a
      decreasing in further therapeutic options, suggesting to earlier consider
      resistance monitoring and ART optimization in this setting.

PMID- 22590589
TI  - Strain-dependent differences in bone development, myeloid hyperplasia, morbidity
      and mortality in ptpn2-deficient mice.
AB  - Single nucleotide polymorphisms in the gene encoding the protein tyrosine
      phosphatase TCPTP (encoded by PTPN2) have been linked with the development of
      autoimmunity. Here we have used Cre/LoxP recombination to generate Ptpn2(ex2-/ex2
      ) mice with a global deficiency in TCPTP on a C57BL/6 background and compared the
      phenotype of these mice to Ptpn2(-/-) mice (BALB/c-129SJ) generated previously by
      homologous recombination and backcrossed onto the BALB/c background. Ptpn2(ex2
      /ex2-) mice exhibited growth retardation and a median survival of 32 days, as
      compared to 21 days for Ptpn2(-/-) (BALB/c) mice, but the overt signs of
      morbidity (hunched posture, piloerection, decreased mobility and diarrhoea)
      evident in Ptpn2(-/-) (BALB/c) mice were not detected in Ptpn2(ex2-/ex2-) mice.
      At 14 days of age, bone development was delayed in Ptpn2(-/-) (BALB/c) mice. This
      was associated with increased trabecular bone mass and decreased bone remodeling,
      a phenotype that was not evident in Ptpn2(ex2-/ex2-) mice. Ptpn2(ex2-/ex2-) mice
      had defects in erythropoiesis and B cell development as evident in Ptpn2(-/-)
      (BALB/c) mice, but not splenomegaly and did not exhibit an accumulation of
      myeloid cells in the spleen as seen in Ptpn2(-/-) (BALB/c) mice. Moreover, thymic
      atrophy, another feature of Ptpn2(-/-) (BALB/c) mice, was delayed in Ptpn2(ex2
      /ex2-) mice and preceded by an increase in thymocyte positive selection and a
      concomitant increase in lymph node T cells. Backcrossing Ptpn2(-/-) (BALB/c) mice
      onto the C57BL/6 background largely recapitulated the phenotype of Ptpn2(ex2-/ex2
      ) mice. Taken together these results reaffirm TCPTP's important role in
      lymphocyte development and indicate that the effects on morbidity, mortality,
      bone development and the myeloid compartment are strain-dependent.

PMID- 22590590
TI  - Extensive transcriptional regulation of chromatin modifiers during human
      neurodevelopment.
AB  - Epigenetic changes, including histone modifications or chromatin remodeling are
      regulated by a large number of human genes. We developed a strategy to study the
      coordinate regulation of such genes, and to compare different cell populations or
      tissues. A set of 150 genes, comprising different classes of epigenetic modifiers
      was compiled. This new tool was used initially to characterize changes during the
      differentiation of human embryonic stem cells (hESC) to central nervous system
      neuroectoderm progenitors (NEP). qPCR analysis showed that more than 60% of the
      examined transcripts were regulated, and >10% of them had a >5-fold increased
      expression. For comparison, we differentiated hESC to neural crest progenitors
      (NCP), a distinct peripheral nervous system progenitor population. Some
      epigenetic modifiers were regulated into the same direction in NEP and NCP, but
      also distinct differences were observed. For instance, the remodeling ATPase
      SMARCA2 was up-regulated >30-fold in NCP, while it remained unchanged in NEP; up
      regulation of the ATP-dependent chromatin remodeler CHD7 was increased in NEP,
      while it was down-regulated in NCP. To compare the neural precursor profiles with
      those of mature neurons, we analyzed the epigenetic modifiers in human cortical
      tissue. This resulted in the identification of 30 regulations shared between all
      cell types, such as the histone methyltransferase SETD7. We also identified new
      markers for post-mitotic neurons, like the arginine methyl transferase PRMT8 and
      the methyl transferase EZH1. Our findings suggest a hitherto unexpected extent of
      regulation, and a cell type-dependent specificity of epigenetic modifiers in
      neurodifferentiation.

PMID- 22590591
TI  - Chitin binding proteins act synergistically with chitinases in Serratia
      proteamaculans 568.
AB  - Genome sequence of Serratia proteamaculans 568 revealed the presence of three
      family 33 chitin binding proteins (CBPs). The three Sp CBPs (Sp CBP21, Sp CBP28
      and Sp CBP50) were heterologously expressed and purified. Sp CBP21 and Sp CBP50
      showed binding preference to beta-chitin, while Sp CBP28 did not bind to chitin
      and cellulose substrates. Both Sp CBP21 and Sp CBP50 were synergistic with four
      chitinases from S. proteamaculans 568 (Sp ChiA, Sp ChiB, Sp ChiC and Sp ChiD) in
      degradation of alpha- and beta-chitin, especially in the presence of external
      electron donor (reduced glutathione). Sp ChiD benefited most from Sp CBP21 or Sp
      CBP50 on alpha-chitin, while Sp ChiB and Sp ChiD had major advantage with these
      Sp CBPs on beta-chitin. Dose responsive studies indicated that both the Sp CBPs
      exhibit synergism >= 0.2 uM. The addition of both Sp CBP21 and Sp CBP50 in
      different ratios to a synergistic mixture did not significantly increase the
      activity. Highly conserved polar residues, important in binding and activity of
      CBP21 from S. marcescens (Sm CBP21), were present in Sp CBP21 and Sp CBP50, while
      Sp CBP28 had only one such polar residue. The inability of Sp CBP28 to bind to
      the test substrates could be attributed to the absence of important polar
      residues.

PMID- 22590592
TI  - Salsolinol facilitates glutamatergic transmission to dopamine neurons in the
      posterior ventral tegmental area of rats.
AB  - Although in vivo evidence indicates that salsolinol, the condensation product of
      acetaldehyde and dopamine, has properties that may contribute to alcohol abuse,
      the underlying mechanisms have not been fully elucidated. We have reported
      previously that salsolinol stimulates dopamine neurons in the posterior ventral
      tegmental area (p-VTA) partly by reducing inhibitory GABAergic transmission, and
      that ethanol increases glutamatergic transmission to VTA-dopamine neurons via the
      activation of dopamine D(1) receptors (D(1)Rs). In this study, we tested the
      hypothesis that salsolinol stimulates dopamine neurons involving activation of
      D(1)Rs. By using whole-cell recordings on p-VTA-dopamine neurons in acute brain
      slices of rats, we found that salsolinol-induced increase in spike frequency of
      dopamine neurons was substantially attenuated by DL-2-amino-5-phosphono-valeric
      acid and 6, 7-dinitroquinoxaline-2, 3-dione, the antagonists of glutamatergic N
      Methyl-D-aspartic acid and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid receptors. Moreover, salsolinol increased the amplitude of evoked excitatory
      postsynaptic currents (EPSCs) and the frequency but not the amplitude of
      spontaneous EPSCs. Additionally, SKF83566, a D(1)R antagonist attenuated the
      salsolinol-induced facilitation of EPSCs and of spontaneous firing of dopamine
      neurons. Our data reveal that salsolinol enhances glutamatergic transmission onto
      dopamine neurons via activation of D(1)Rs at the glutamatergic afferents in
      dopamine neurons, which contributes to salsolinol's stimulating effect on p-VTA
      dopamine neurons. This appears to be a novel mechanism which contributes toward
      rewarding properties of salsolinol.

PMID- 22590593
TI  - A microalbuminuria threshold to predict the risk for the development of diabetic
      retinopathy in type 2 diabetes mellitus patients.
AB  - OBJECTIVE: To test the hypothesis that a microalbuminuria (MA) threshold can help
      predict the risk for the development of diabetic retinopathy (DR) in type 2
      diabetes mellitus (T2DM)_ patients. DESIGN: We conducted a cross-sectional study
      of 4739 subjects with T2DM and a prospective study of 297 subjects with T2DM in
      China respectively. METHODS: Clinical and laboratory data were collected and
      biologic risk factors associated with any DR were analysed. RESULTS: In the cross
      sectional study, we found that MA was an independent risk factor for DR
      development; further, when the patients were divided into MA deciles, odds ratio
      (ORs) of DR for the patients in the sixth MA decile (10.7 mg/24 h) was 1.579-fold
      (1.161-2.147) compared to that for patients in the first MA decile. Furthermore,
      the OR of DR increased with a gradual increase in MA levels. Similarly, in the
      prospective study, during a mean follow-up of 4.5 years, we found that 51
      patients (29.0%) of the 176 subjects with high MA level (10.7-30 mg/24 h)
      developed DR, while 17 patients (14.1%) of the 121 subjects with lower MA (<10.7
      mg/24 h) developed DR, and the relative risk ratio of the development of DR is
      2.13(95% CI, 1.58-3.62, P<0.001). CONCLUSION: These data suggest that an MA
      threshold can predict the risk for the development of DR in type 2 diabetes
      mellitus, although it is still within the traditionally established normal range.

PMID- 22590594
TI  - NOXA-induced alterations in the Bax/Smac axis enhance sensitivity of ovarian
      cancer cells to cisplatin.
AB  - Ovarian cancer is the most common cause of death from gynecologic malignancy.
      Deregulation of p53 and/or p73-associated apoptotic pathways contribute to the
      platinum-based resistance in ovarian cancer. NOXA, a pro-apoptotic BH3-only
      protein, is identified as a transcription target of p53 and/or p73. In this
      study, we found that genetic variants of Bcl-2 proteins exist among cisplatin
      sensitive and -resistant ovarian cancer cells, and the responses of NOXA and Bax
      to cisplatin are regulated mainly by p53. We further evaluated the effect of NOXA
      on cisplatin. NOXA induced apoptosis and sensitized A2780s and SKOV3 cells to
      cisplatin in vitro and in vivo. The effects were mediated by elevated Bax
      expression, enhanced caspase activation, release of Cyt C and Smac into the
      cytosol. Furthermore, gene silencing of Bax or Smac significantly attenuated NOXA
      and/or cisplatin-induced apoptosis in chemosensitive A2780s cells, whereas
      overexpression of Bax or addition of Smac-N7 peptide significantly increased NOXA
      and/or cisplatin-induced apoptosis in chemoresistant SKOV3 cells. To our
      knowledge, these data suggest a new mechanism by which NOXA chemosensitized
      ovarian cancer cells to cisplatin by inducing alterations in the Bax/Smac axis.
      Taken together, our findings show that NOXA is potentially useful as a
      chemosensitizer in ovarian cancer therapy.

PMID- 22590595
TI  - Genes important for catalase activity in Enterococcus faecalis.
AB  - Little in general is known about how heme proteins are assembled from their
      constituents in cells. The Gram-positive bacterium Enterococcus faecalis cannot
      synthesize heme and does not depend on it for growth. However, when supplied with
      heme in the growth medium the cells can synthesize two heme proteins; catalase
      (KatA) and cytochrome bd (CydAB). To identify novel factors important for
      catalase biogenesis libraries of E. faecalis gene insertion mutants were
      generated using two different types of transposons. The libraries of mutants were
      screened for clones deficient in catalase activity using a colony zymogram
      staining procedure. Analysis of obtained clones identified, in addition to katA
      (encoding the catalase enzyme protein), nine genes distributed over five
      different chromosomal loci. No factors with a dedicated essential role in
      catalase biogenesis or heme trafficking were revealed, but the results indicate
      the RNA degradosome (srmB, rnjA), an ABC-type oligopeptide transporter (oppBC), a
      two-component signal transducer (etaR), and NADH peroxidase (npr) as being
      important for expression of catalase activity in E. faecalis. It is demonstrated
      that catalase biogenesis in E. faecalis is independent of the CydABCD proteins
      and that a conserved proline residue in the N-terminal region of KatA is
      important for catalase assembly.

PMID- 22590597
TI  - Modelling transmission of vector-borne pathogens shows complex dynamics when
      vector feeding sites are limited.
AB  - The relationship between species richness and the prevalence of vector-borne
      disease has been widely studied with a range of outcomes. Increasing the number
      of host species for a pathogen may decrease infection prevalence (dilution
      effect), increase it (amplification), or have no effect. We derive a general
      model, and a specific implementation, which show that when the number of vector
      feeding sites on each host is limiting, the effects on pathogen dynamics of host
      population size are more complex than previously thought. The model examines
      vector-borne disease in the presence of different host species that are either
      competent or incompetent (i.e. that cannot transmit the pathogen to vectors) as
      reservoirs for the pathogen. With a single host species present, the basic
      reproduction ratio R(0) is a non-monotonic function of the population size of
      host individuals (H), i.e. a value [Formula: see text] exists that maximises
      R(0). Surprisingly, if [Formula: see text] a reduction in host population size
      may actually increase R(0). Extending this model to a two-host species system,
      incompetent individuals from the second host species can alter the value of
      [Formula: see text] which may reverse the effect on pathogen prevalence of host
      population reduction. We argue that when vector-feeding sites on hosts are
      limiting, the net effect of increasing host diversity might not be correctly
      predicted using simple frequency-dependent epidemiological models.

PMID- 22590596
TI  - A quantitative study of the mechanisms behind thymic atrophy in Galphai2
      deficient mice during colitis development.
AB  - Mice deficient for the G protein subunit Galphai2 spontaneously develop colitis,
      a chronic inflammatory disease associated with dysregulated T cell responses. We
      and others have previously demonstrated a thymic involution in these mice and an
      aberrant thymocyte dynamics. The Galphai2(-/-) mice have a dramatically reduced
      fraction of double positive thymocytes and an increased fraction of single
      positive (SP) thymocytes. In this study, we quantify a number of critical
      parameters in order to narrow down the underlying mechanisms that cause the
      dynamical changes of the thymocyte development in the Galphai2(-/-) mice. Our
      data suggest that the increased fraction of SP thymocytes results only from a
      decreased number of DP thymocytes, since the number of SP thymocytes in the
      Galphai2(-/-) mice is comparable to the control littermates. By measuring the
      frequency of T cell receptor excision circles (TRECs) in the thymocytes, we
      demonstrate that the number of cell divisions the Galphai2(-/-) SP thymocytes
      undergo is comparable to SP thymocytes from control littermates. In addition, our
      data show that the mature SP CD4(+) and CD8(+) thymocytes divide to the same
      extent before they egress from the thymus. By estimating the number of peripheral
      TREC(+) T lymphocytes and their death rate, we could calculate the daily
      egression of thymocytes. Galphai2(-/-) mice with no/mild and moderate colitis
      were found to have a slower export rate in comparison to the control littermates.
      The quantitative measurements in this study suggest a number of dynamical changes
      in the thymocyte development during the progression of colitis.

PMID- 22590598
TI  - Fish is food--the FAO's fish price index.
AB  - World food prices hit an all-time high in February 2011 and are still almost two
      and a half times those of 2000. Although three billion people worldwide use
      seafood as a key source of animal protein, the Food and Agriculture Organization
      (FAO) of the United Nations-which compiles prices for other major food categories
      has not tracked seafood prices. We fill this gap by developing an index of global
      seafood prices that can help to understand food crises and may assist in averting
      them. The fish price index (FPI) relies on trade statistics because seafood is
      heavily traded internationally, exposing non-traded seafood to price competition
      from imports and exports. Easily updated trade data can thus proxy for domestic
      seafood prices that are difficult to observe in many regions and costly to update
      with global coverage. Calculations of the extent of price competition in
      different countries support the plausibility of reliance on trade data. Overall,
      the FPI shows less volatility and fewer price spikes than other food price
      indices including oils, cereals, and dairy. The FPI generally reflects seafood
      scarcity, but it can also be separated into indices by production technology,
      fish species, or region. Splitting FPI into capture fisheries and aquaculture
      suggests increased scarcity of capture fishery resources in recent years, but
      also growth in aquaculture that is keeping pace with demand. Regionally, seafood
      price volatility varies, and some prices are negatively correlated. These
      patterns hint that regional supply shocks are consequential for seafood prices in
      spite of the high degree of seafood tradability.

PMID- 22590599
TI  - Muramyl dipeptide induces NOD2-dependent Ly6C(high) monocyte recruitment to the
      lungs and protects against influenza virus infection.
AB  - Bacterial peptidoglycan-derived muramyl dipeptide (MDP) and derivatives have long
      recognized antiviral properties but their mechanism of action remains unclear. In
      recent years, the pattern-recognition receptor NOD2 has been shown to mediate
      innate responses to MDP. Here, we show that MDP treatment of mice infected with
      Influenza A virus (IAV) significantly reduces mortality, viral load and pulmonary
      inflammation in a NOD2-dependent manner. Importantly, the induction of type I
      interferon (IFN) and CCL2 chemokine was markedly increased in the lungs following
      MDP treatment and correlated with a NOD2-dependent enhancement in circulating
      monocytes. Mechanistically, the protective effect of MDP could be explained by
      the NOD2-dependent transient increase in recruitment of Ly6C(high) "inflammatory"
      monocytes and, to a lesser extent, neutrophils to the lungs. Indeed, impairment
      in both Ly6C(high) monocyte recruitment and survival observed in infected Nod2-/-
      mice treated with MDP was recapitulated in mice deficient for the chemokine
      receptor CCR2 required for CCL2-mediated Ly6C(high) monocyte migration from the
      bone marrow into the lungs. MDP-induced pulmonary monocyte recruitment occurred
      normally in IAV-infected and MDP-treated Ips-1-/- mice. However, IPS-1 was
      required for improved survival upon MDP treatment. Finally, mycobacterial N
      glycolyl MDP was more potent than N-acetyl MDP expressed by most bacteria at
      reducing viral burden while both forms of MDP restored pulmonary function
      following IAV challenge. Overall, our work sheds light on the antiviral mechanism
      of a clinically relevant bacterial-derived compound and identifies the NOD2
      pathway as a potential therapeutic target against IAV.

PMID- 22590600
TI  - Multiple measures reveal antiretroviral adherence successes and challenges in HIV
      infected Ugandan children.
AB  - BACKGROUND: Adherence to HIV antiretroviral therapy (ART) among children in
      developing settings is poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: To
      understand the level, distribution, and correlates of ART adherence behavior, we
      prospectively determined monthly ART adherence through multiple measures and six
      monthly HIV RNA levels among 121 Ugandan children aged 2-10 years for one year.
      Median adherence levels were 100% by three-day recall, 97.4% by 30-day visual
      analog scale, 97.3% by unannounced pill count/liquid formulation weights, and
      96.3% by medication event monitors (MEMS). Interruptions in MEMS adherence of >=
      48 hours were seen in 57.0% of children; 36.3% had detectable HIV RNA at one
      year. Only MEMS correlated significantly with HIV RNA levels (r = -0.25, p =
      0.04). Multivariable regression found the following to be associated with <90%
      MEMS adherence: hospitalization of child (adjusted odds ratio [AOR] 3.0, 95%
      confidence interval [CI] 1.6-5.5; p = 0.001), liquid formulation use (AOR 1.4,
      95%CI 1.0-2.0; p = 0.04), and caregiver's alcohol use (AOR 3.1, 95%CI 1.8-5.2;
      p<0.0001). Child's use of co-trimoxazole (AOR 0.5, 95%CI 0.4-0.9; p = 0.009),
      caregiver's use of ART (AOR 0.6, 95%CI 0.4-0.9; p = 0.03), possible caregiver
      depression (AOR 0.6, 95%CI 0.4-0.8; p = 0.001), and caregiver feeling ashamed of
      child's HIV status (AOR 0.5, 95%CI 0.3-0.6; p<0.0001) were protective against
      <90% MEMS adherence. Change in drug manufacturer (AOR 4.1, 95%CI 1.5-11.5; p =
      0.009) and caregiver's alcohol use (AOR 5.5, 95%CI 2.8-10.7; p<0.0001) were
      associated with >= 48-hour interruptions by MEMS, while second-line ART (AOR 0.3,
      95%CI 0.1-0.99; p = 0.049) and increasing assets (AOR 0.7, 95%CI 0.6-0.9; p =
      0.0007) were protective against these interruptions. CONCLUSIONS/SIGNIFICANCE:
      Adherence success depends on a well-established medication taking routine,
      including caregiver support and adequate education on medication changes.
      Caregiver-reported depression and shame may reflect fear of poor outcomes,
      functioning as motivation for the child to adhere. Further research is needed to
      better understand and build on these key influential factors for adherence
      intervention development.

PMID- 22590601
TI  - A functional screen provides evidence for a conserved, regulatory, juxtamembrane
      phosphorylation site in guanylyl cyclase a and B.
AB  - Kinase homology domain (KHD) phosphorylation is required for activation of
      guanylyl cyclase (GC)-A and -B. Phosphopeptide mapping identified multiple
      phosphorylation sites in GC-A and GC-B, but these approaches have difficulty
      identifying sites in poorly detected peptides. Here, a functional screen was
      conducted to identify novel sites. Conserved serines or threonines in the KHDs of
      phosphorylated receptor GCs were mutated to alanine and tested for reduced
      hormone to detergent activity ratios. Mutation of Ser-489 in GC-B to alanine but
      not glutamate reduced the activity ratio to 60% of wild type (WT) levels. Similar
      results were observed with Ser-473, the homologous site in GC-A. Receptors
      containing glutamates for previously identified phosphorylation sites (GC-A-6E
      and GC-B-6E) were activated to ~20% of WT levels but the additional glutamate
      substitution for S473 or S489 increased activity to near WT levels. Substrate
      velocity assays indicated that GC-B-WT-S489E and GC-B-6E-S489E had lower Km
      values and that WT-GC-B-S489A, GC-B-6E and GC-B-6E-S489A had higher Km values
      than WT-GC-B. Homologous desensitization was enhanced when GC-A contained the
      S473E substitution, and GC-B-6E-S489E was resistant to inhibition by a calcium
      elevating treatment or protein kinase C activation--processes that
      dephosphorylate GC-B. Mass spectrometric detection of a synthetic phospho-Ser-473
      containing peptide was 200-1300-fold less sensitive than other phosphorylated
      peptides and neither mass spectrometric nor (32)PO(4) co-migration studies
      detected phospho-Ser-473 or phospho-Ser-489 in cells. We conclude that Ser-473
      and Ser-489 are Km-regulating phosphorylation sites that are difficult to detect
      using current methods.

PMID- 22590602
TI  - Human peripheral blood antibodies with long HCDR3s are established primarily at
      original recombination using a limited subset of germline genes.
AB  - A number of antibodies that efficiently neutralize microbial targets contain long
      heavy chain complementarity determining region 3 (HCDR3) loops. For HIV, several
      of the most broad and potently neutralizing antibodies have exceptionally long
      HCDR3s. Two broad potently neutralizing HIV-specific antibodies, PG9 and PG16,
      exhibit secondary structure. Two other long HCDR3 antibodies, 2F5 and 4E10,
      protect against mucosal challenge with SHIV. Induction of such long HCDR3
      antibodies may be critical to the design of an effective vaccine strategy for HIV
      and other pathogens, however it is unclear at present how to induce such
      antibodies. Here, we present genetic evidence that human peripheral blood
      antibodies containing long HCDR3s are not primarily generated by insertions
      introduced during the somatic hypermutation process. Instead, they are typically
      formed by processes occurring as part of the original recombination event. Thus,
      the response of B cells encoding antibodies with long HCDR3s results from
      selection of unusual clones from the naive repertoire rather than through
      accumulation of insertions. These antibodies typically use a small subset of D
      and J gene segments that are particularly suited to encoding long HCDR3s,
      resulting in the incorporation of highly conserved genetic elements in the
      majority of antibody sequences encoding long HCDR3s.

PMID- 22590603
TI  - The genome characteristics and predicted function of methyl-group oxidation
      pathway in the obligate aceticlastic methanogens, Methanosaeta spp.
AB  - In this work, we report the complete genome sequence of an obligate aceticlastic
      methanogen, Methanosaeta harundinacea 6Ac. Genome comparison indicated that the
      three cultured Methanosaeta spp., M. thermophila, M. concilii and M. harundinacea
      6Ac, each carry an entire suite of genes encoding the proteins involved in the
      methyl-group oxidation pathway, a pathway whose function is not well documented
      in the obligately aceticlastic methanogens. Phylogenetic analysis showed that the
      methyl-group oxidation-involving proteins, Fwd, Mtd, Mch, and Mer from
      Methanosaeta strains cluster with the methylotrophic methanogens, and were not
      closely related to those from the hydrogenotrophic methanogens. Quantitative PCR
      detected the expression of all genes for this pathway, albeit ten times lower
      than the genes for aceticlastic methanogenesis in strain 6Ac. Western blots also
      revealed the expression of fwd and mch, genes involved in methyl-group oxidation.
      Moreover, (13)C-labeling experiments suggested that the Methanosaeta strains
      might use the pathway as a methyl oxidation shunt during the aceticlastic
      metabolism. Because the mch mutants of Methanosarcina barkeri or M. acetivorans
      failed to grow on acetate, we suggest that Methanosaeta may use methyl-group
      oxidation pathway to generate reducing equivalents, possibly for biomass
      synthesis. An fpo operon, which encodes an electron transport complex for the
      reduction of CoM-CoB heterodisulfide, was found in the three genomes of the
      Methanosaeta strains. However, an incomplete protein complex lacking the FpoF
      subunit was predicted, as the gene for this protein was absent. Thus, F(420)H(2)
      was predicted not to serve as the electron donor. In addition, two gene clusters
      encoding the two types of heterodisulfide reductase (Hdr), hdrABC, and hdrED,
      respectively, were found in the three Methanosaeta genomes. Quantitative PCR
      determined that the expression of hdrED was about ten times higher than hdrABC,
      suggesting that hdrED plays a major role in aceticlastic methanogenesis.

PMID- 22590604
TI  - Current and historical drivers of landscape genetic structure differ in core and
      peripheral salamander populations.
AB  - With predicted decreases in genetic diversity and greater genetic differentiation
      at range peripheries relative to their cores, it can be difficult to distinguish
      between the roles of current disturbance versus historic processes in shaping
      contemporary genetic patterns. To address this problem, we test for differences
      in historic demography and landscape genetic structure of coastal giant
      salamanders (Dicamptodon tenebrosus) in two core regions (Washington State,
      United States) versus the species' northern peripheral region (British Columbia,
      Canada) where the species is listed as threatened. Coalescent-based demographic
      simulations were consistent with a pattern of post-glacial range expansion, with
      both ancestral and current estimates of effective population size being much
      larger within the core region relative to the periphery. However, contrary to
      predictions of recent human-induced population decline in the less genetically
      diverse peripheral region, there was no genetic signature of population size
      change. Effects of current demographic processes on genetic structure were
      evident using a resistance-based landscape genetics approach. Among core
      populations, genetic structure was best explained by length of the growing season
      and isolation by resistance (i.e. a 'flat' landscape), but at the periphery,
      topography (slope and elevation) had the greatest influence on genetic structure.
      Although reduced genetic variation at the range periphery of D. tenebrosus
      appears to be largely the result of biogeographical history rather than recent
      impacts, our analyses suggest that inherent landscape features act to alter
      dispersal pathways uniquely in different parts of the species' geographic range,
      with implications for habitat management.

PMID- 22590606
TI  - Spontaneous innovation for future deception in a male chimpanzee.
AB  - BACKGROUND: The ability to invent means to deceive others, where the deception
      lies in the perceptually or contextually detached future, appears to require the
      coordination of sophisticated cognitive skills toward a single goal. Meanwhile
      innovation for a current situation has been observed in a wide range of species.
      Planning, on the one hand, and the social cognition required for deception on the
      other, have been linked to one another, both from a co-evolutionary and a
      neuroanatomical perspective. Innovation and deception have also been suggested to
      be connected in their nature of relying on novelty. METHODOLOGY/PRINCIPAL
      FINDINGS: We report on systematic observations suggesting innovation for future
      deception by a captive male chimpanzee (Pan troglodytes). As an extension of
      previously described behaviour--caching projectiles for later throwing at zoo
      visitors--the chimpanzee, again in advance, manufactured concealments from hay,
      as well as used naturally occurring concealments. All were placed near the
      visitors' observation area, allowing the chimpanzee to make throws before the
      crowd could back off. We observed what was likely the first instance of this
      innovation. Further observations showed that the creation of future-oriented
      concealments became the significantly preferred strategy. What is more, the
      chimpanzee appeared consistently to combine two deceptive strategies: hiding
      projectiles and inhibiting dominance display behaviour. CONCLUSIONS/SIGNIFICANCE:
      The findings suggest that chimpanzees can represent the future behaviours of
      others while those others are not present, as well as take actions in the current
      situation towards such potential future behaviours. Importantly, the behaviour of
      the chimpanzee produced a future event, rather than merely prepared for an event
      that had been reliably re-occurring in the past. These findings might indicate
      that the chimpanzee recombined episodic memories in perceptual simulations.

PMID- 22590605
TI  - Gender and weight shape brain dynamics during food viewing.
AB  - Hemodynamic imaging results have associated both gender and body weight to
      variation in brain responses to food-related information. However, the spatio
      temporal brain dynamics of gender-related and weight-wise modulations in food
      discrimination still remain to be elucidated. We analyzed visual evoked
      potentials (VEPs) while normal-weighted men (n = 12) and women (n = 12)
      categorized photographs of energy-dense foods and non-food kitchen utensils. VEP
      analyses showed that food categorization is influenced by gender as early as 170
      ms after image onset. Moreover, the female VEP pattern to food categorization co
      varied with participants' body weight. Estimations of the neural generator
      activity over the time interval of VEP modulations (i.e. by means of a
      distributed linear inverse solution [LAURA]) revealed alterations in prefrontal
      and temporo-parietal source activity as a function of image category and
      participants' gender. However, only neural source activity for female responses
      during food viewing was negatively correlated with body-mass index (BMI) over the
      respective time interval. Women showed decreased neural source activity
      particularly in ventral prefrontal brain regions when viewing food, but not non
      food objects, while no such associations were apparent in male responses to food
      and non-food viewing. Our study thus indicates that gender influences are already
      apparent during initial stages of food-related object categorization, with small
      variations in body weight modulating electrophysiological responses especially in
      women and in brain areas implicated in food reward valuation and intake control.
      These findings extend recent reports on prefrontal reward and control circuit
      responsiveness to food cues and the potential role of this reactivity pattern in
      the susceptibility to weight gain.

PMID- 22590607
TI  - Identification of new agonists and antagonists of the insect odorant receptor co
      receptor subunit.
AB  - BACKGROUND: Insects detect attractive and aversive chemicals using several
      families of chemosensory receptors, including the OR family of olfactory
      receptors, making these receptors appealing targets for the control of insects.
      Insect ORs are odorant-gated ion channels, comprised of at least one common
      subunit (the odorant receptor co-receptor subunit, Orco) and at least one
      variable odorant specificity subunit. Each of the many ORs of an insect species
      is activated or inhibited by an unique set of odorants that interact with the
      variable odorant specificity subunits, making the development of OR directed
      insect control agents complex and laborious. However, several N-,2-substituted
      triazolothioacetamide compounds (VUAA1, VU0450667 and VU0183254) were recently
      shown to act directly on the highly conserved Orco subunit, suggesting that
      broadly active compounds can be developed. We have explored the chemical space
      around the VUAA1 structure in order to identify new Orco ligands. PRINCIPAL
      FINDINGS: We screened ORs from several insect species, using heterologous
      expression in Xenopus oocytes and an electrophysiological assay, with a panel of
      22 compounds structurally related to VUAA1. By varying the nitrogen position in
      the pyridine ring and altering the moieties decorating the phenyl ring, we
      identified two new agonists and a series of competitive antagonists. Screening
      smaller compounds, similar to portions of the VUAA1 structure, also yielded
      competitive antagonists. Importantly, we show that Orco antagonists inhibit
      odorant activation of ORs from several insect species. Detailed examination of
      one antagonist demonstrated inhibition to be through a non-competitive mechanism.
      CONCLUSIONS: A similar pattern of agonist and antagonist sensitivity displayed by
      Orco subunits from different species suggests a highly conserved binding site
      structure. The susceptibility to inhibition of odorant activation by Orco
      antagonism is conserved across disparate insect species, suggesing the ligand
      binding site on Orco as a promising target for the development of novel, broadly
      active insect repellants.

PMID- 22590608
TI  - Poor spontaneous and oxytocin-stimulated contractility in human myometrium from
      postdates pregnancies.
AB  - Prolongation of pregnancy i.e. going more than 10 days over the estimated due
      date, complicates up to 10% of all pregnancies and is associated with increased
      risk to both mother and fetus. Despite the obvious need for contractions of the
      uterus to end pregnancy, there have been no studies directly examining the role
      of uterine smooth muscle, myometrium, in the aetiology of prolonged pregnancy.
      This study tested the hypothesis that the intrinsic contractile characteristics
      of myometrium taken from women with prolonged pregnancy (>41 weeks and 3 days)
      was reduced compared to those delivering at term (39-41 weeks). We recruited
      women undergoing Caesarean Section (CS) delivery either pre-labour (n = 27) or in
      labour (n = 66) at term or postdates. The contractile ability of the postdates
      myometrium, whether spontaneous or elicited by oxytocin or high-K solution, was
      significantly reduced compared to term myometrium. These differences remained
      when adjusted for parity and other maternal characteristics. The findings
      remained significant when expressed per cross sectional area. Histological
      examination revealed no differences between the two groups. The contractile
      differences were however related to intracellular Ca transients suggesting an
      effect of [Ca] on reduced force production in the postdates group. In summary,
      myometrium from prolonged pregnancies contracts poorly in vitro even when
      stimulated with oxytocin and in active labour. Responses to high K(+) and
      measurements of Ca suggest that alterations in excitation contraction coupling,
      rather than any histological changes of the myometrium, may underlie the
      differences between term and postdates myometrium. We show that postdates
      pregnancy is associated with poor myometrial activity and suggest that this may
      contribute to increased myometrial quiescence and hence, prolonged gestation.

PMID- 22590609
TI  - Intrapericardial delivery of gelfoam enables the targeted delivery of Periostin
      peptide after myocardial infarction by inducing fibrin clot formation.
AB  - BACKGROUND: Administration of a recombinant peptide of Periostin (rPN) has
      recently been shown to stimulate cardiomyocyte proliferation and angiogenesis
      after myocardial infarction (MI) [1]. However, strategies for targeting the
      delivery of rPN to the heart are lacking. Intrapericardial administration of drug
      eluting hydrogels may provide a clinically viable strategy for increasing
      myocardial retention, therapeutic efficacy, and bioactivity of rPN and to
      decrease systemic re-circulation. METHODS AND RESULTS: We investigated the
      ability of intrapericardial injections of drug-eluting hydrogels to deliver and
      prolong the release of rPN to the myocardium in a large animal model of
      myocardial infarction. Gelfoam is an FDA-approved hemostatic material commonly
      used in surgery, and is known to stimulate fibrin clot formation. We show that
      Gelfoam disks loaded with rPN, when implanted within the pericardium or
      peritoneum of mammals becomes encapsulated within a non-fibrotic fibrin-rich
      hydrogel, prolonging the in vitro and in vivo release of rPN. Administration into
      the pericardial cavity of pigs, following a complete occlusion of the left
      anterior descending artery, leads to greater induction of cardiomyocyte mitosis,
      increased cardiomyocyte cell cycle activity, and enhanced angiogenesis compared
      to direct injection of rPN alone. CONCLUSIONS: The results of this study suggest
      that intrapericardial drug delivery of Gelfoam, enhanced by triggered clot
      formation, can be used to effectively deliver rPN to the myocardium in a
      clinically relevant model of myocardial infarction. The work presented here
      should enhance the translational potential of pharmaceutical-based strategies
      that must be targeted to the myocardium.

PMID- 22590610
TI  - Effect of stocking rate on soil-atmosphere CH4 flux during spring freeze-thaw
      cycles in a northern desert steppe, China.
AB  - BACKGROUND: Methane (CH(4)) uptake by steppe soils is affected by a range of
      specific factors and is a complex process. Increased stocking rate promotes
      steppe degradation, with unclear consequences for gas exchanges. To assess the
      effects of grazing management on CH(4) uptake in desert steppes, we investigated
      soil-atmosphere CH(4) exchange during the winter-spring transition period.
      METHODOLOGY/MAIN FINDING: The experiment was conducted at twelve grazing plots
      denoting four treatments defined along a grazing gradient with three
      replications: non-grazing (0 sheep/ha, NG), light grazing (0.75 sheep/ha, LG),
      moderate grazing (1.50 sheep/ha, MG) and heavy grazing (2.25 sheep/ha, HG). Using
      an automatic cavity ring-down spectrophotometer, we measured CH(4) fluxes from
      March 1 to April 29 in 2010 and March 2 to April 27 in 2011. According to the
      status of soil freeze-thaw cycles (positive and negative soil temperatures
      occurred in alternation), the experiment was divided into periods I and II.
      Results indicate that mean CH(4) uptake in period I (7.51 ug CH(4)-C m(-2) h(-1))
      was significantly lower than uptake in period II (83.07 ug CH(4)-C m(-2) h(-1)).
      Averaged over 2 years, CH(4) fluxes during the freeze-thaw period were -84.76 ug
      CH(4)-C m(-2) h(-1) (NG), -88.76 ug CH(4)-C m(-2) h(-1) (LG), -64.77 ug CH(4)-C
      m(-2) h(-1) (MG) and -28.80 ug CH(4)-C m(-2) h(-1) (HG).
      CONCLUSIONS/SIGNIFICANCE: CH(4) uptake activity is affected by freeze-thaw cycles
      and stocking rates. CH(4) uptake is correlated with the moisture content and
      temperature of soil. MG and HG decreases CH(4) uptake while LG exerts a
      considerable positive impact on CH(4) uptake during spring freeze-thaw cycles in
      the northern desert steppe in China.

PMID- 22590611
TI  - Market powers predict reciprocal grooming in golden snub-nosed monkeys
      (Rhinopithecus roxellana).
AB  - Social grooming is a common form of affiliative behavior in primates. Biological
      market theory suggests that grooming can be traded either for grooming or other
      social commodities and services. When no other services are exchanged, grooming
      is predicted to be approximately reciprocated within a dyad. In contrast, the
      amount of reciprocal grooming should decrease as other offered services increase.
      We studied grooming patterns between polygamous male and female in golden snub
      nosed monkeys (Rhinopithecus roxellana) from the Qinling Mountains of central
      China and found that about 29.7% of grooming bouts were reciprocated. However,
      the durations of grooming bouts offered and returned was asymmetrical within
      dyads. In bisexual dyads, more grooming was initiated by females than males,
      which became more pronounced as the number of females per one-male unit
      increased. The rate of copulation per day for each female was positively
      correlated with the total duration of grooming time females invested in males..
      Females without an infant (non-mothers) directed more grooming towards females
      with an infant (mothers) and were significantly more likely to be non
      reciprocated. There was a significant negative relationship between non-mother
      and mother grooming duration and the rate of infants per female in each one-male
      unit. High-ranking females also received more grooming from low-ranking females
      than vice versa. The rate of food-related aggressive interactions was per day for
      low-ranking females was negatively correlated with the duration of grooming that
      low-ranking females gave to high-ranking females. Our results showed that
      grooming reciprocation in R. roxellana was discrepancy. This investment
      reciprocity rate could be explained by the exchange of other social services in
      lieu of grooming.

PMID- 22590612
TI  - Ischemia-reperfusion injury and pregnancy initiate time-dependent and robust
      signs of up-regulation of cardiac progenitor cells.
AB  - To explore how cardiac regeneration and cell turnover adapts to disease,
      different forms of stress were studied for their effects on the cardiac
      progenitor cell markers c-Kit and Isl1, the early cardiomyocyte marker Nkx2.5,
      and mast cells. Adult female rats were examined during pregnancy, after
      myocardial infarction and ischemia-reperfusion injury with/out insulin like
      growth factor-1(IGF-1) and hepatocyte growth factor (HGF). Different cardiac sub
      domains were analyzed at one and two weeks post-intervention, both at the mRNA
      and protein levels. While pregnancy and myocardial infarction up-regulated Nkx2.5
      and c-Kit (adjusted for mast cell activation), ischemia-reperfusion injury
      induced the strongest up-regulation which occurred globally throughout the entire
      heart and not just around the site of injury. This response seems to be partly
      mediated by increased endogenous production of IGF-1 and HGF. Contrary to c-Kit,
      Isl1 was not up-regulated by pregnancy or myocardial infarction while ischemia
      reperfusion injury induced not a global but a focal up-regulation in the outflow
      tract and also in the peri-ischemic region, correlating with the up-regulation of
      endogenous IGF-1. The addition of IGF-1 and HGF did boost the endogenous
      expression of IGF and HGF correlating to focal up-regulation of Isl1. c-Kit
      expression was not further influenced by the exogenous growth factors. This
      indicates that there is a spatial mismatch between on one hand c-Kit and Nkx2.5
      expression and on the other hand Isl1 expression. In conclusion, ischemia
      reperfusion injury was the strongest stimulus with both global and focal
      cardiomyocyte progenitor cell marker up-regulations, correlating to the
      endogenous up-regulation of the growth factors IGF-1 and HGF. Also pregnancy
      induced a general up-regulation of c-Kit and early Nkx2.5+ cardiomyocytes
      throughout the heart. Utilization of these pathways could provide new strategies
      for the treatment of cardiac disease.

PMID- 22590613
TI  - Non-antioxidant properties of alpha-tocopherol reduce the anticancer activity of
      several protein kinase inhibitors in vitro.
AB  - The antioxidant properties of alpha-tocopherol have been proposed to play a
      beneficial chemopreventive role against cancer. However, emerging data also
      indicate that it may exert contrasting effects on the efficacy of
      chemotherapeutic treatments when given as dietary supplement, being in that case
      harmful for patients. This dual role of alpha-tocopherol and, in particular, its
      effects on the efficacy of anticancer drugs remains poorly documented. For this
      purpose, we studied here, using high throughput flow cytometry, the direct impact
      of alpha-tocopherol on apoptosis and cell cycle arrest induced by different
      cytotoxic agents on various models of cancer cell lines in vitro. Our results
      indicate that physiologically relevant concentrations of alpha-tocopherol
      strongly compromise the cytotoxic and cytostatic action of various protein kinase
      inhibitors (KI), while other classes of chemotherapeutic agents or apoptosis
      inducers are unaffected by this vitamin. Interestingly, these anti
      chemotherapeutic effects of alpha-tocopherol appear to be unrelated to its
      antioxidant properties since a variety of other antioxidants were completely
      neutral toward KI-induced cell cycle arrest and cell death. In conclusion, our
      data suggest that dietary alpha-tocopherol could limit KI effects on tumour
      cells, and, by extent, that this could result in a reduction of the clinical
      efficacy of anti-cancer treatments based on KI molecules.

PMID- 22590614
TI  - Immunogenicity and protective capacity of a virosomal respiratory syncytial virus
      vaccine adjuvanted with monophosphoryl lipid A in mice.
AB  - Respiratory Syncytial Virus (RSV) is a major cause of viral brochiolitis in
      infants and young children and is also a significant problem in elderly and
      immuno-compromised adults. To date there is no efficacious and safe RSV vaccine,
      partially because of the outcome of a clinical trial in the 1960s with a formalin
      inactivated RSV vaccine (FI-RSV). This vaccine caused enhanced respiratory
      disease upon exposure to the live virus, leading to increased morbidity and the
      death of two children. Subsequent analyses of this incident showed that FI-RSV
      induces a Th2-skewed immune response together with poorly neutralizing
      antibodies. As a new approach, we used reconstituted RSV viral envelopes, i.e.
      virosomes, with incorporated monophosphoryl lipid A (MPLA) adjuvant to enhance
      immunogenicity and to skew the immune response towards a Th1 phenotype.
      Incorporation of MPLA stimulated the overall immunogenicity of the virosomes
      compared to non-adjuvanted virosomes in mice. Intramuscular administration of the
      vaccine led to the induction of RSV-specific IgG2a levels similar to those
      induced by inoculation of the animals with live RSV. These antibodies were able
      to neutralize RSV in vitro. Furthermore, MPLA-adjuvanted RSV virosomes induced
      high amounts of IFNgamma and low amounts of IL5 in both spleens and lungs of
      immunized and subsequently challenged animals, compared to levels of these
      cytokines in animals vaccinated with FI-RSV, indicating a Th1-skewed response.
      Mice vaccinated with RSV-MPLA virosomes were protected from live RSV challenge,
      clearing the inoculated virus without showing signs of lung pathology. Taken
      together, these data demonstrate that RSV-MPLA virosomes represent a safe and
      efficacious vaccine candidate which warrants further evaluation.

PMID- 22590615
TI  - An abundant tissue macrophage population in the adult murine heart with a
      distinct alternatively-activated macrophage profile.
AB  - Cardiac tissue macrophages (cTMs) are a previously uncharacterised cell type that
      we have identified and characterise here as an abundant GFP(+) population within
      the adult Cx(3)cr1(GFP/+) knock-in mouse heart. They comprise the predominant
      myeloid cell population in the myocardium, and are found throughout myocardial
      interstitial spaces interacting directly with capillary endothelial cells and
      cardiomyocytes. Flow cytometry-based immunophenotyping shows that cTMs exhibit
      canonical macrophage markers. Gene expression analysis shows that cTMs
      (CD45(+)CD11b(+)GFP(+)) are distinct from mononuclear CD45(+)CD11b(+)GFP(+) cells
      sorted from the spleen and brain of adult Cx(3)cr1(GFP/+) mice. Gene expression
      profiling reveals that cTMs closely resemble alternatively-activated anti
      inflammatory M2 macrophages, expressing a number of M2 markers, including Mrc1,
      CD163, and Lyve-1. While cTMs perform normal tissue macrophage homeostatic
      functions, they also exhibit a distinct phenotype, involving secretion of
      salutary factors (including IGF-1) and immune modulation. In summary, the
      characterisation of cTMs at the cellular and molecular level defines a
      potentially important role for these cells in cardiac homeostasis.

PMID- 22590616
TI  - Polydendrocytes display large lineage plasticity following focal cerebral
      ischemia.
AB  - Polydendrocytes (also known as NG2 glial cells) constitute a fourth major glial
      cell type in the adult mammalian central nervous system (CNS) that is distinct
      from other cell types. Although much evidence suggests that these cells are
      multipotent in vitro, their differentiation potential in vivo under physiological
      or pathophysiological conditions is still controversial.To follow the fate of
      polydendrocytes after CNS pathology, permanent middle cerebral artery occlusion
      (MCAo), a commonly used model of focal cerebral ischemia, was carried out on
      adult NG2creBAC:ZEG double transgenic mice, in which enhanced green fluorescent
      protein (EGFP) is expressed in polydendrocytes and their progeny. The phenotype
      of the EGFP(+) cells was analyzed using immunohistochemistry and the patch-clamp
      technique 3, 7 and 14 days after MCAo. In sham-operated mice (control), EGFP(+)
      cells in the cortex expressed protein markers and displayed electrophysiological
      properties of polydendrocytes and oligodendrocytes. We did not detect any co
      labeling of EGFP with neuronal, microglial or astroglial markers in this region,
      thus proving polydendrocyte unipotent differentiation potential under
      physiological conditions. Three days after MCAo the number of EGFP(+) cells in
      the gliotic tissue dramatically increased when compared to control animals, and
      these cells displayed properties of proliferating cells. However, in later phases
      after MCAo a large subpopulation of EGFP(+) cells expressed protein markers and
      electrophysiological properties of astrocytes that contribute to the formation of
      glial scar. Importantly, some EGFP(+) cells displayed membrane properties typical
      for neural precursor cells, and moreover these cells expressed doublecortin (DCX)
      -a marker of newly-derived neuronal cells. Taken together, our data indicate that
      polydendrocytes in the dorsal cortex display multipotent differentiation
      potential after focal ischemia.

PMID- 22590617
TI  - Subdomain location of mutations in cardiac actin correlate with type of
      functional change.
AB  - Determining the molecular mechanisms that lead to the development of heart
      failure will help us gain better insight into the most costly health problem in
      the Western world. To understand the roles that the actin protein plays in the
      development of heart failure, we have taken a systematic approach toward
      characterizing human cardiac actin mutants that have been associated with either
      hypertrophic or dilated cardiomyopathy. Seven known cardiac actin mutants were
      expressed in a baculovirus system, and their intrinsic properties were studied.
      In general, the changes to the properties of the actin proteins themselves were
      subtle. The R312H variant exhibited reduced stability, with a T(m) of 53.6 
      degrees C compared to 56.8  degrees C for WT actin, accompanied with increased
      polymerization critical concentration and Pi release rate, and a marked increase
      in nucleotide release rates. Substitution of methionine for leucine at amino acid
      305 showed no impact on the stability, nucleotide release rates, or DNase-I
      inhibition ability of the actin monomer; however, during polymerization, a 2-fold
      increase in Pi release was observed. Increases to both the T(m) and DNase-I
      inhibition activity suggested interactions between E99K actin molecules under
      monomer-promoting conditions. Y166C actin had a higher critical concentration
      resulting in a lower Pi release rate due to reduced filament-forming potential.
      The locations of mutations on the ACTC protein correlated with the molecular
      effects; in general, mutations in subdomain 3 affected the stability of the ACTC
      protein or affect the polymerization of actin filaments, while mutations in
      subdomains 1 and 4 more likely affect protein-protein interactions.

PMID- 22590618
TI  - NK cells promote Th-17 mediated corneal barrier disruption in dry eye.
AB  - BACKGROUND: The conjunctiva contains a specialized population of lymphocytes that
      reside in the epithelium, named intraepithelial lymphocytes (IEL).
      METHODOLOGY/PRINCIPAL FINDINGS: Here we characterized the IEL population prior to
      and after experimental desiccating stress (DS) for 5 or 10 days (DS5, DS10) and
      evaluated the effect of NK depletion on DS. The frequency of IELs in normal
      murine conjunctiva was CD3(+)CD103(+) (~22%), CD3(+)gammadelta(+) (~9.6%),
      CD3(+)NK(+) (2%), CD3(-)NK(+) (~4.4%), CD3(+)CD8alpha (~0.9%), and CD4 (~0.6%).
      Systemic depletion of NK cells prior and during DS led to a decrease in the
      frequency of total and activated DCs, a decrease in T helper-17(+) cells in the
      cervical lymph nodes and generation of less pathogenic CD4(+)T cells. B6.nude
      recipient mice of adoptively transferred CD4(+)T cells isolated from NK-depleted
      DS5 donor mice showed significantly less corneal barrier disruption, lower levels
      of IL-17A, CCL20 and MMP-3 in the cornea epithelia compared to recipients of
      control CD4(+)T cells. CONCLUSIONS/SIGNIFICANCE: Taken together, these results
      show that the NK IELs are involved in the acute immune response to desiccation
      induced dry eye by activating DC, which in turn coordinate generation of the
      pathogenic Th-17 response.

PMID- 22590619
TI  - Citizen participation in patient prioritization policy decisions: an empirical
      and experimental study on patients' characteristics.
AB  - Health systems worldwide are grappling with the need to control costs to maintain
      system viability. With the combination of worsening economic conditions, an aging
      population and reductions in tax revenues, the pressures to make structural
      changes are expected to continue growing. Common cost control mechanisms, e.g.
      curtailment of patient access and treatment prioritization, are likely to be
      adversely viewed by citizens. It seems therefore wise to include them in the
      decision making processes that lead up to policy changes. In the context of a
      multilevel iterative mixed-method design a quantitative survey representative of
      the German population (N = 2031) was conducted to probe the acceptance of
      priority setting in medicine and to explore the practicability of direct public
      involvement. Here we focus on preferences for patients' characteristics (medical
      aspects, lifestyle and socio-economic status) as possible criteria for
      prioritizing medical services. A questionnaire with closed response options was
      fielded to gain insight into attitudes toward broad prioritization criteria of
      patient groups. Furthermore, a discrete choice experiment was used as a rigorous
      approach to investigate citizens' preferences toward specific criteria level in
      context of other criteria. Both the questionnaire and the discrete choice
      experiment were performed with the same sample. The citizens' own health and
      social situation are included as explanatory variables. Data were evaluated using
      corresponding analysis, contingency analysis, logistic regression and a
      multinomial exploded logit model. The results show that some medical criteria are
      highly accepted for prioritizing patients whereas socio-economic criteria are
      rejected.

PMID- 22590620
TI  - Direct molecular detection and genotyping of Borrelia burgdorferi from whole
      blood of patients with early Lyme disease.
AB  - Direct molecular tests in blood for early Lyme disease can be insensitive due to
      low amount of circulating Borrelia burgdorferi DNA. To address this challenge, we
      have developed a sensitive strategy to both detect and genotype B. burgdorferi
      directly from whole blood collected during the initial patient visit. This
      strategy improved sensitivity by employing 1.25 mL of whole blood, a novel pre
      enrichment of the entire specimen extract for Borrelia DNA prior to a multi-locus
      PCR and electrospray ionization mass spectrometry detection assay. We evaluated
      the assay on blood collected at the initial presentation from 21 endemic area
      patients who had both physician-diagnosed erythema migrans (EM) and positive two
      tiered serology either at the initial visit or at a follow-up visit after three
      weeks of antibiotic therapy. Results of this DNA analysis showed detection of B.
      burgdorferi in 13 of 21 patients (62%). In most cases the new assay also provided
      the B. burgdorferi genotype. The combined results of our direct detection assay
      with initial physician visit serology resulted in the detection of early Lyme
      disease in 19 of 21 (90%) of patients at the initial visit. In 5 of 21 cases we
      demonstrate the ability to detect B. burgdorferi in early Lyme disease directly
      from whole blood specimens prior to seroconversion.

PMID- 22590622
TI  - Satellite tracking of manta rays highlights challenges to their conservation.
AB  - We describe the real-time movements of the last of the marine mega-vertebrate
      taxa to be satellite tracked - the giant manta ray (or devil fish, Manta
      birostris), the world's largest ray at over 6 m disc width. Almost nothing is
      known about manta ray movements and their environmental preferences, making them
      one of the least understood of the marine mega-vertebrates. Red listed by the
      International Union for the Conservation of Nature as 'Vulnerable' to extinction,
      manta rays are known to be subject to direct and incidental capture and some
      populations are declining. Satellite-tracked manta rays associated with seasonal
      upwelling events and thermal fronts off the Yucatan peninsula, Mexico, and made
      short-range shuttling movements, foraging along and between them. The majority of
      locations were received from waters shallower than 50 m deep, representing
      thermally dynamic and productive waters. Manta rays remained in the Mexican
      Exclusive Economic Zone for the duration of tracking but only 12% of tracking
      locations were received from within Marine Protected Areas (MPAs). Our results on
      the spatio-temporal distribution of these enigmatic rays highlight opportunities
      and challenges to management efforts.

PMID- 22590621
TI  - Persistent oxytetracycline exposure induces an inflammatory process that improves
      regenerative capacity in zebrafish larvae.
AB  - BACKGROUND: The excessive use of antibiotics in aquaculture can adversely affect
      not only the environment, but also fish themselves. In this regard, there is
      evidence that some antibiotics can activate the immune system and reduce their
      effectiveness. None of those studies consider in detail the adverse inflammatory
      effect that the antibiotic remaining in the water may cause to the fish. In this
      work, we use the zebrafish to analyze quantitatively the effects of persistent
      exposure to oxytetracycline, the most common antibiotic used in fish farming.
      METHODOLOGY: We developed a quantitative assay in which we exposed zebrafish
      larvae to oxytetracycline for a period of 24 to 96 hrs. In order to determinate
      if the exposure causes any inflammation reaction, we evaluated neutrophils
      infiltration and quantified their total number analyzing the Tg(mpx:GFP)(i114)
      transgenic line by fluorescence stereoscope, microscope and flow cytometry
      respectively. On the other hand, we characterized the process at a molecular
      level by analyzing several immune markers (il-1beta, il-10, lysC, mpx, cyp1a) at
      different time points by qPCR. Finally, we evaluated the influence of the
      inflammation triggered by oxytetracycline on the regeneration capacity in the
      lateral line. CONCLUSIONS: Our results suggest that after 48 hours of exposure,
      the oxytetracycline triggered a widespread inflammation process that persisted
      until 96 hours of exposure. Interestingly, larvae that developed an inflammation
      process showed an improved regeneration capacity in the mechanosensory system
      lateral line.

PMID- 22590623
TI  - Diabetes alters intracellular calcium transients in cardiac endothelial cells.
AB  - Diabetic cardiomyopathy (DCM) is a diabetic complication, which results in
      myocardial dysfunction independent of other etiological factors. Abnormal
      intracellular calcium ([Ca(2+)](i)) homeostasis has been implicated in DCM and
      may precede clinical manifestation. Studies in cardiomyocytes have shown that
      diabetes results in impaired [Ca(2+)](i) homeostasis due to altered sarcoplasmic
      reticulum Ca(2+) ATPase (SERCA) and sodium-calcium exchanger (NCX) activity.
      Importantly, altered calcium homeostasis may also be involved in diabetes
      associated endothelial dysfunction, including impaired endothelium-dependent
      relaxation and a diminished capacity to generate nitric oxide (NO), elevated cell
      adhesion molecules, and decreased angiogenic growth factors. However, the effect
      of diabetes on Ca(2+) regulatory mechanisms in cardiac endothelial cells (CECs)
      remains unknown. The objective of this study was to determine the effect of
      diabetes on [Ca(2+)](i) homeostasis in CECs in the rat model (streptozotocin
      induced) of DCM. DCM-associated cardiac fibrosis was confirmed using picrosirius
      red staining of the myocardium. CECs isolated from the myocardium of diabetic and
      wild-type rats were loaded with Fura-2, and UTP-evoked [Ca(2+)](i) transients
      were compared under various combinations of SERCA, sarcoplasmic reticulum Ca(2+)
      ATPase (PMCA) and NCX inhibitors. Diabetes resulted in significant alterations in
      SERCA and NCX activities in CECs during [Ca(2+)](i) sequestration and efflux,
      respectively, while no difference in PMCA activity between diabetic and wild-type
      cells was observed. These results improve our understanding of how diabetes
      affects calcium regulation in CECs, and may contribute to the development of new
      therapies for DCM treatment.

PMID- 22590624
TI  - Eukaryotic protein recruitment into the Chlamydia inclusion: implications for
      survival and growth.
AB  - Chlamydia trachomatis (Ct) is an obligate intracellular human pathogen that
      multiplies within a parasitophorous vacuole called an inclusion. We report that
      the location of several host-cell proteins present in the cytosol, the nucleus,
      and membranes was altered during Ct development. The acyl-CoA synthetase enzyme
      ACSL3 and the soluble acyl-CoA binding protein ACBD6 were mobilized from
      organelle membranes and the nucleus, respectively, into the lumen of the
      inclusion. The nuclear protein ZNF23, a pro-apoptosis factor, was also
      translocated into the inclusion lumen. ZNF23, among other proteins, might be
      targeted by Ct to inhibit host cell apoptosis, thereby enabling bacterial
      survival. In contrast, the acyl-CoA:lysophosphatidylcholine acyltransferase
      LPCAT1, an endoplasmic reticulum membrane protein, was recruited to the inclusion
      membrane. The coordinated action of ACBD6, ACSL3 and LPCAT1 likely supports
      remodeling and scavenging of host lipids into bacterial-specific moieties
      essential to Ct growth. To our knowledge, these are the first identified host
      proteins known to be intercepted and translocated into the inclusion.

PMID- 22590625
TI  - Perifosine as a potential novel anti-cancer agent inhibits EGFR/MET-AKT axis in
      malignant pleural mesothelioma.
AB  - BACKGROUND: PI3K/AKT signalling pathway is aberrantly active and plays a critical
      role for cell cycle progression of human malignant pleural mesothelioma (MMe)
      cells. AKT is one of the important cellular targets of perifosine, a novel bio
      available alkylphospholipid that has displayed significant anti-proliferative
      activity in vitro and in vivo in several human tumour model systems and is
      currently being tested in clinical trials. METHODS: We tested Perifosine activity
      on human mesothelial cells and different mesothelioma cell lines, in order to
      provide evidence of its efficacy as single agent and combined therapy. RESULTS:
      We demonstrate here that perifosine, currently being evaluated as an anti-cancer
      agent in phase 1 and 2 clinical trials, caused a dose-dependent reduction of AKT
      activation, at concentrations causing MMe cell growth arrest. In this study we
      firstly describe that MMe cells express aside from AKT1 also AKT3 and that either
      the myristoylated, constitutively active, forms of the two proteins, abrogated
      perifosine-mediated cell growth inhibition. Moreover, we describe here a novel
      mechanism of perifosine that interferes, upstream of AKT, affecting EGFR and MET
      phosphorylation. Finally, we demonstrate a significant increase in cell toxicity
      when MMe cells were treated with perifosine in combination with cisplatin.
      CONCLUSIONS: This study provides a novel mechanism of action of perifosine,
      directly inhibiting EGFR/MET-AKT1/3 axis, providing a rationale for a novel
      translational approach to the treatment of MMe.

PMID- 22590626
TI  - Retinotopic maps, spatial tuning, and locations of human visual areas in surface
      coordinates characterized with multifocal and blocked FMRI designs.
AB  - The localization of visual areas in the human cortex is typically based on
      mapping the retinotopic organization with functional magnetic resonance imaging
      (fMRI). The most common approach is to encode the response phase for a slowly
      moving visual stimulus and to present the result on an individual's reconstructed
      cortical surface. The main aims of this study were to develop complementary
      general linear model (GLM)-based retinotopic mapping methods and to characterize
      the inter-individual variability of the visual area positions on the cortical
      surface. We studied 15 subjects with two methods: a 24-region multifocal
      checkerboard stimulus and a blocked presentation of object stimuli at different
      visual field locations. The retinotopic maps were based on weighted averaging of
      the GLM parameter estimates for the stimulus regions. In addition to localizing
      visual areas, both methods could be used to localize multiple retinotopic regions
      of-interest. The two methods yielded consistent retinotopic maps in the visual
      areas V1, V2, V3, hV4, and V3AB. In the higher-level areas IPS0, VO1, LO1, LO2,
      TO1, and TO2, retinotopy could only be mapped with the blocked stimulus
      presentation. The gradual widening of spatial tuning and an increase in the
      responses to stimuli in the ipsilateral visual field along the hierarchy of
      visual areas likely reflected the increase in the average receptive field size.
      Finally, after registration to Freesurfer's surface-based atlas of the human
      cerebral cortex, we calculated the mean and variability of the visual area
      positions in the spherical surface-based coordinate system and generated
      probability maps of the visual areas on the average cortical surface. The inter
      individual variability in the area locations decreased when the midpoints were
      calculated along the spherical cortical surface compared with volumetric
      coordinates. These results can facilitate both analysis of individual functional
      anatomy and comparisons of visual cortex topology across studies.

PMID- 22590627
TI  - Selective activation of p120ctn-Kaiso signaling to unlock contact inhibition of
      ARPE-19 cells without epithelial-mesenchymal transition.
AB  - Contact-inhibition ubiquitously exists in non-transformed cells and explains the
      poor regenerative capacity of in vivo human retinal pigment epithelial cells
      (RPE) during aging, injury and diseases. RPE injury or degeneration may unlock
      mitotic block mediated by contact inhibition but may also promote epithelial
      mesenchymal transition (EMT) contributing to retinal blindness. Herein, we
      confirmed that EMT ensued in post-confluent ARPE-19 cells when contact inhibition
      was disrupted with EGTA followed by addition of EGF and FGF-2 because of
      activation of canonical Wnt and Smad/ZEB signaling. In contrast, knockdown of
      p120-catenin (p120) unlocked such mitotic block by activating p120/Kaiso, but not
      activating canonical Wnt and Smad/ZEB signaling, thus avoiding EMT. Nuclear BrdU
      labeling was correlated with nuclear release of Kaiso through p120 nuclear
      translocation, which was associated with activation of RhoA-ROCK signaling,
      destabilization of microtubules. Prolonged p120 siRNA knockdown followed by
      withdrawal further expanded RPE into more compact monolayers with a normal
      phenotype and a higher density. This new strategy based on selective activation
      of p120/Kaiso but not Wnt/beta-catenin signaling obviates the need of using
      single cells and the risk of EMT, and may be deployed to engineer surgical grafts
      containing RPE and other tissues.

PMID- 22590628
TI  - Hypothalamic orexin--a neurons are involved in the response of the brain stress
      system to morphine withdrawal.
AB  - Both the hypothalamus-pituitary-adrenal (HPA) axis and the extrahypothalamic
      brain stress system are key elements of the neural circuitry that regulates the
      negative states during abstinence from chronic drug exposure. Orexins have
      recently been hypothesized to modulate the extended amygdala and to contribute to
      the negative emotional state associated with dependence. This study examined the
      impact of chronic morphine and withdrawal on the lateral hypothalamic (LH) orexin
      A (OXA) gene expression and activity as well as OXA involvement in the brain
      stress response to morphine abstinence. Male Wistar rats received chronic
      morphine followed by naloxone to precipitate withdrawal. The selective OX1R
      antagonist SB334867 was used to examine whether orexins' activity is related to
      somatic symptoms of opiate withdrawal and alterations in HPA axis and extended
      amygdala in rats dependent on morphine. OXA mRNA was induced in the hypothalamus
      during morphine withdrawal, which was accompanied by activation of OXA neurons in
      the LH. Importantly, SB334867 attenuated the somatic symptoms of withdrawal, and
      reduced morphine withdrawal-induced c-Fos expression in the nucleus accumbens
      (NAc) shell, bed nucleus of stria terminalis, central amygdala and hypothalamic
      paraventricular nucleus, but did not modify the HPA axis activity. These results
      highlight a critical role of OXA signalling, via OX1R, in activation of brain
      stress system to morphine withdrawal and suggest that all orexinergic
      subpopulations in the lateral hypothalamic area contribute in this response.

PMID- 22590629
TI  - GABA maintains the proliferation of progenitors in the developing chick ciliary
      marginal zone and non-pigmented ciliary epithelium.
AB  - GABA is more than the main inhibitory neurotransmitter found in the adult CNS.
      Several studies have shown that GABA regulates the proliferation of progenitor
      and stem cells. This work examined the effects of the GABA(A) receptor system on
      the proliferation of retinal progenitors and non-pigmented ciliary epithelial
      (NPE) cells. qRT-PCR and whole-cell patch-clamp electrophysiology were used to
      characterize the GABA(A) receptor system. To quantify the effects on
      proliferation by GABA(A) receptor agonists and antagonists, incorporation of
      thymidine analogues was used. The results showed that the NPE cells express
      functional extrasynaptic GABA(A) receptors with tonic properties and that low
      concentration of GABA is required for a baseline level of proliferation.
      Antagonists of the GABA(A) receptors decreased the proliferation of dissociated
      E12 NPE cells. Bicuculline also had effects on progenitor cell proliferation in
      intact E8 and E12 developing retina. The NPE cells had low levels of the Cl
      transporter KCC2 compared to the mature retina, suggesting a depolarising role
      for the GABA(A) receptors. Treatment with KCl, which is known to depolarise
      membranes, prevented some of the decreased proliferation caused by inhibition of
      the GABA(A) receptors. This supported the depolarising role for the GABA(A)
      receptors. Inhibition of L-type voltage-gated Ca(2+) channels (VGCCs) reduced the
      proliferation in the same way as inhibition of the GABA(A) receptors. Inhibition
      of the channels increased the expression of the cyclin-dependent kinase inhibitor
      p27(KIP1), along with the reduced proliferation. These results are consistent
      with that when the membrane potential indirectly regulates cell proliferation
      with hyperpolarisation of the membrane potential resulting in decreased cell
      division. The increased expression of p27(KIP1) after inhibition of either the
      GABA(A) receptors or the L-type VGCCs suggests a link between the GABA(A)
      receptors, membrane potential, and intracellular Ca(2+) in regulating the cell
      cycle.

PMID- 22590630
TI  - Allelic expression changes in Medaka (Oryzias latipes) hybrids between inbred
      strains derived from genetically distant populations.
AB  - Variations in allele expressions between genetically distant populations are one
      of the most important factors which affects their morphological and physiological
      variations. These variations are caused by natural mutations accumulated in their
      habitats. It has been reported that allelic expression differences in the hybrids
      of genetically distant populations are different from parental strains. In that
      case, there is a possibility that allelic expression changes lead to novel
      phenotypes in hybrids. Based on genomic information of the genetically distant
      populations, quantification and comparison of allelic expression changes make
      importance of regulatory sequences (cis-acting factors) or upstream regulatory
      factors (trans-acting modulators) for these changes clearer. In this study, we
      focused on two Medaka inbred strains, Hd-rR and HNI, derived from genetically
      distant populations and their hybrids. They are highly polymorphic and we can
      utilize whole-genome information. To analyze allelic expression changes, we
      established a method to quantify and compare allele-specific expressions of 11
      genes between the parental strains and their reciprocal hybrids. In intestines of
      reciprocal hybrids, allelic expression was either similar or different in
      comparison with the parental strains. Total expressions in Hd-rR and HNI were
      tissue-dependent in the case of HPRT1, with high up-regulation of Hd-rR allele
      expression in liver. The proportion of genes with differential allelic expression
      in Medaka hybrids seems to be the same as that in other animals, despite the high
      SNP rate in the genomes of the two inbred strains. It is suggested that each
      tissue of the strain difference in trans-acting modulators is more important than
      polymorphisms in cis-regulatory sequences in producing the allelic expression
      changes in reciprocal hybrids.

PMID- 22590631
TI  - Chaoborus and gasterosteus anti-predator responses in Daphnia pulex are mediated
      by independent cholinergic and gabaergic neuronal signals.
AB  - Many prey species evolved inducible defense strategies that protect effectively
      against predation threats. Especially the crustacean Daphnia emerged as a model
      system for studying the ecology and evolution of inducible defenses. Daphnia
      pulex e.g. shows different phenotypic adaptations against vertebrate and
      invertebrate predators. In response to the invertebrate phantom midge larvae
      Chaoborus (Diptera) D. pulex develops defensive morphological defenses
      (neckteeth). Cues originating from predatory fish result in life history changes
      in which resources are allocated from somatic growth to reproduction. While there
      are hints that responses against Chaoborus cues are transmitted involving
      cholinergic neuronal pathways, nothing is known about the neurophysiology
      underlying the transmission of fish related cues. We investigated the
      neurophysiological basis underlying the activation of inducible defenses in D.
      pulex using induction assays with the invertebrate predator Chaoborus and the
      three-spined stickleback Gasterosteus aculeatus. Predator-specific cues were
      combined with neuro-effective substances that stimulated or inhibited the
      cholinergic and gabaergic nervous system. We show that cholinergic-dependent
      pathways are involved in the perception and transmission of Chaoborus cues, while
      GABA was not involved. Thus, the cholinergic nervous system independently
      mediates the development of morphological defenses in response to Chaoborus cues.
      In contrast, only the inhibitory effect of GABA significantly influence fish
      induced life history changes, while the application of cholinergic stimulants had
      no effect in combination with fish related cues. Our results show that
      cholinergic stimulation mediates signal transmission of Chaoborus cues leading to
      morphological defenses. Fish cues, which are responsible for predator-specific
      life history adaptations involve gabaergic control. Our study shows that both
      pathways are independent and thus potentially allow for adjustment of responses
      to variable predation regimes.

PMID- 22590633
TI  - Photoperiod influences growth and mll (mixed-lineage leukaemia) expression in
      Atlantic cod.
AB  - Photoperiod is associated to phenotypic plasticity of somatic growth in several
      teleost species. However, the molecular mechanisms underlying this phenomenon are
      currently unknown but it is likely that epigenetic regulation by
      methyltransferases is involved. The MLL (mixed-lineage leukaemia) family
      comprises histone methyltransferases that play a critical role in regulating gene
      expression during early development in mammals. So far, these genes have received
      scant attention in teleost fish. In the present study, the mean weight of
      Atlantic cod juveniles reared under continuous illumination was found to be 13%
      greater than those kept under natural photoperiod conditions for 120 days. We
      newly determined cDNA sequences of five mll (mll1, mll2, mll3a, mll4b and mll5)
      and two setd1 (setd1a and setd1ba) paralogues from Atlantic cod. Phylogenetic
      analysis revealed that the cod genes clustered within the appropriate mll clade
      and comparative mapping of mll paralogues showed that these genes lie within a
      region of conserved synteny among teleosts. All mll and setd1 genes were highly
      expressed in gonads and fast muscle of adult cod, albeit at different levels, and
      they were differentially regulated with photoperiod in muscle of juvenile fish.
      Following only one day of exposure to constant light, mll1, mll4b and setd1a were
      up to 57% lower in these fish compared to the natural photoperiod group. In
      addition, mRNA expression of myogenic regulatory factors (myog and myf-5) and
      pax7 in fast muscle was also affected by different photoperiod conditions.
      Notably, myog was significantly elevated in the continuous illumination group
      throughout the time course of the experiment. The absence of a day/night cycle is
      associated with a generalised decrease in mll expression concomitant with an
      increase in myog transcript levels in fast muscle of Atlantic cod, which may be
      involved in the observed epigenetic regulation of growth by photoperiod in this
      species.

PMID- 22590632
TI  - Phosphorus is associated with coronary artery disease in patients with preserved
      renal function.
AB  - High serum phosphorus levels have been associated with mortality and
      cardiovascular events in patients with chronic kidney disease and in the general
      population. In addition, high phosphorus levels have been shown to induce
      vascular calcification and endothelial dysfunction in vitro. The aim of this
      study was to evaluate the relation of phosphorus and coronary calcification and
      atherosclerosis in the setting of normal renal function. This was a cross
      sectional study involving 290 patients with suspected coronary artery disease and
      undergoing elective coronary angiography, with a creatinine clearance >60
      ml/min/1.73 m(2). Coronary artery obstruction was assessed by the Friesinger
      score and coronary artery calcification by multislice computed tomography. Serum
      phosphorus was higher in patients with an Agatston score >10 than in those with
      an Agatston score <= 10 (3.63 +/- 0.55 versus 3.49 +/- 0.52 mg/dl; p = 0.02). In
      the patients with Friesinger scores >4, serum phosphorus was higher (3.6 +/- 0.5
      versus 3.5 +/- 0.6 mg/dl, p = 0.04) and median intact fibroblast growth factor 23
      was lower (40.3 pg/ml versus 45.7 pg/ml, p = 0.01). Each 0.1-mg/dl higher serum
      phosphate was associated with a 7.4% higher odds of having a Friesinger score >4
      (p = 0.03) and a 6.1% greater risk of having an Agatston score >10 (p = 0.01).
      Fibroblast growth factor 23 was a negative predictor of Friesinger score (p =
      0.002). In conclusion, phosphorus is positively associated with coronary artery
      calcification and obstruction in patients with suspected coronary artery disease
      and preserved renal function.

PMID- 22590634
TI  - Extracellular nucleotides inhibit insulin receptor signaling, stimulate autophagy
      and control lipoprotein secretion.
AB  - Hyperglycemia is associated with abnormal plasma lipoprotein metabolism and with
      an elevation in circulating nucleotide levels. We evaluated how extracellular
      nucleotides may act to perturb hepatic lipoprotein secretion. Adenosine
      diphosphate (ADP) (>10 uM) acts like a proteasomal inhibitor to stimulate apoB100
      secretion and inhibit apoA-I secretion from human liver cells at 4 h and 24 h.
      ADP blocks apoA-I secretion by stimulating autophagy. The nucleotide increases
      cellular levels of the autophagosome marker, LC3-II, and increases co
      localization of LC3 with apoA-I in punctate autophagosomes. ADP affects autophagy
      and apoA-I secretion through P2Y(13). Overexpression of P2Y(13) increases
      cellular LC3-II levels by ~50% and blocks induction of apoA-I secretion.
      Conversely, a siRNA-induced reduction in P2Y(13) protein expression of 50% causes
      a similar reduction in cellular LC3-II levels and a 3-fold stimulation in apoA-I
      secretion. P2Y(13) gene silencing blocks the effects of ADP on autophagy and apoA
      I secretion. A reduction in P2Y(13) expression suppresses ERK1/2 phosphorylation,
      increases the phosphorylation of IR-beta and protein kinase B (Akt) >3-fold, and
      blocks the inhibition of Akt phosphorylation by TNFalpha and ADP. Conversely,
      increasing P2Y(13) expression significantly inhibits insulin-induced
      phosphorylation of insulin receptor (IR-beta) and Akt, similar to that observed
      after treatment with ADP. Nucleotides therefore act through P2Y(13), ERK1/2 and
      insulin receptor signaling to stimulate autophagy and affect hepatic lipoprotein
      secretion.

PMID- 22590635
TI  - A calibration protocol for population-specific accelerometer cut-points in
      children.
AB  - PURPOSE: To test a field-based protocol using intermittent activities
      representative of children's physical activity behaviours, to generate
      behaviourally valid, population-specific accelerometer cut-points for sedentary
      behaviour, moderate, and vigorous physical activity. METHODS: Twenty-eight
      children (46% boys) aged 10-11 years wore a hip-mounted uniaxial GT1M ActiGraph
      and engaged in 6 activities representative of children's play. A validated direct
      observation protocol was used as the criterion measure of physical activity.
      Receiver Operating Characteristics (ROC) curve analyses were conducted with four
      semi-structured activities to determine the accelerometer cut-points. To examine
      classification differences, cut-points were cross-validated with free-play and
      DVD viewing activities. RESULTS: Cut-points of <= 372, >2160 and >4806 counts *
      min(-1) representing sedentary, moderate and vigorous intensity thresholds,
      respectively, provided the optimal balance between the related needs for
      sensitivity (accurately detecting activity) and specificity (limiting
      misclassification of the activity). Cross-validation data demonstrated that these
      values yielded the best overall kappa scores (0.97; 0.71; 0.62), and a high
      classification agreement (98.6%; 89.0%; 87.2%), respectively. Specificity values
      of 96-97% showed that the developed cut-points accurately detected physical
      activity, and sensitivity values (89-99%) indicated that minutes of activity were
      seldom incorrectly classified as inactivity. CONCLUSION: The development of an
      inexpensive and replicable field-based protocol to generate behaviourally valid
      and population-specific accelerometer cut-points may improve the classification
      of physical activity levels in children, which could enhance subsequent
      intervention and observational studies.

PMID- 22590636
TI  - Prevalence and determinants of metabolic syndrome among women in Chinese rural
      areas.
AB  - BACKGROUND AND AIMS: Metabolic syndrome (MS) is prevalent in recent years but few
      data is reported in the rural areas in China. The aim of this study was to
      examine MS prevalence and its risk factors among women in rural China. METHODS
      AND RESULTS: The Nantong Metabolic Syndrome Study (NMSS), a population based
      cross-sectional study, was conducted during 2007-2008 in Nantong, China. In
      person interviews, blood glucose and lipid measurements were completed for 13,505
      female participants aged 18-74 years. The International Diabetes Federation
      (IDF), the US Third Report of the National Cholesterol Education Program, the
      Adult Treatment Panel (ATPIII) and modified ATPIII for Asian population has
      determined three criteria of MS. These criteria for MS were used and compared in
      this study. The prevalence of MS was 22.0%, 16.9% and 23.3% according to IDF,
      ATPIII and ATPIII-modified criteria, respectively. Levels of agreement of these
      criteria for MS were above 0.75. We found that vigorous-intensity of occupational
      physical activity was associated with a low prevalence of MS with OR of 0.76 (95%
      confidence interval (CI): 0.63-0.91). Rice wine drinkers (alcohol >12.8 g/day)
      had about 34% low risks of developing MS with OR of 0.66 (95% CI: 0.48-0.91),
      compared with non-drinkers. Odds ratio of MS was 1.81 (95% CI: 1.15-2.84) in
      women who smoked more than 20 pack-years, compared to non-smokers. Odds ratio of
      MS was 1.56 (95% CI: 1.25-1.95) in women who had familial history of diseases,
      including hypertension, diabetes and stroke, compared to women without familial
      history of those diseases. CONCLUSION: MS is highly prevalent among women in
      rural China. Both physical activity and rice wine consumption play a protective
      role, while family history and smoking are risk factors in MS development.
      Educational programs should be established for promoting healthy lifestyles and
      appropriate interventions in rural China.

PMID- 22590637
TI  - Malabaricone-A induces a redox imbalance that mediates apoptosis in U937 cell
      line.
AB  - BACKGROUND: The 'two-faced' character of reactive oxygen species (ROS) plays an
      important role in cancer biology by acting both as secondary messengers in
      intracellular signaling cascades and sustaining the oncogenic phenotype of cancer
      cells, while on the other hand, it triggers an oxidative assault that causes a
      redox imbalance translating into an apoptotic cell death. PRINCIPAL FINDINGS:
      Using a tetrazolium [{3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2
      (4-sulfophenyl}-2H-tetrazolium] based cell viability assay, we evaluated the
      cytotoxicity of a plant derived diarylnonanoid, malabaricone-A on leukemic cell
      lines U937 and MOLT-3. This cytotoxicity hinged on its ability to cause a redox
      imbalance via its ability to increase ROS, measured by flow cytometry using 5
      (and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate and by decreasing
      glutathione peroxidase activity. This redox imbalance mediated apoptosis was
      evident by an increase in cytosolic [Ca(2+)], externalization of phosphatidyl
      serine as also depolarization of the mitochondrial membrane potential as measured
      by flow cytometry. There was concomitant peroxidation of cardiolipin, release of
      free cytochrome c to cytosol along with activation of caspases 9, 8 and 3. This
      led to cleavage of the DNA repair enzyme, poly (ADP-ribose) polymerase that
      caused DNA damage as proved by labeling with 4',6-diamidino-2-phenylindole
      (DAPI); furthermore, terminal deoxy ribonucleotide transferase catalysed
      incorporation of deoxy uridine triphosphate confirmed DNA nicking and was
      accompanied by arrest of cell cycle progression. CONCLUSIONS: Taken together,
      compounds like MAL-A having pro-oxidant activity mediate their cytotoxicity in
      leukemic cells via induction of oxidative stress triggering a caspase dependent
      apoptosis.

PMID- 22590638
TI  - Genomic sequencing and comparative analysis of Epstein-Barr virus genome isolated
      from primary nasopharyngeal carcinoma biopsy.
AB  - Whether certain Epstein-Barr virus (EBV) strains are associated with pathogenesis
      of nasopharyngeal carcinoma (NPC) is still an unresolved question. In the present
      study, EBV genome contained in a primary NPC tumor biopsy was amplified by
      Polymerase Chain Reaction (PCR), and sequenced using next-generation (Illumina)
      and conventional dideoxy-DNA sequencing. The EBV genome, designated HKNPC1
      (Genbank accession number JQ009376) is a type 1 EBV of approximately 171.5 kb.
      The virus appears to be a uniform strain in line with accepted monoclonal nature
      of EBV in NPC but is heterogeneous at 172 nucleotide positions. Phylogenetic
      analysis with the four published EBV strains, B95-8, AG876, GD1, and GD2,
      indicated HKNPC1 was more closely related to the Chinese NPC patient-derived
      strains, GD1 and GD2. HKNPC1 contains 1,589 single nucleotide variations (SNVs)
      and 132 insertions or deletions (indels) in comparison to the reference EBV
      sequence (accession number NC007605). When compared to AG876, a strain derived
      from Ghanaian Burkitt's lymphoma, we found 322 SNVs, of which 76 were non
      synonymous SNVs and were shared amongst the Chinese GD1, GD2 and HKNPC1 isolates.
      We observed 88 non-synonymous SNVs shared only by HKNPC1 and GD2, the only other
      NPC tumor-derived strain reported thus far. Non-synonymous SNVs were mainly found
      in the latent, tegument and glycoprotein genes. The same point mutations were
      found in glycoprotein (BLLF1 and BALF4) genes of GD1, GD2 and HKNPC1 strains and
      might affect cell type specific binding. Variations in LMP1 and EBNA3B epitopes
      and mutations in Cp (11404 C>T) and Qp (50134 G>C) found in GD1, GD2 and HKNPC1
      could potentially affect CD8(+) T cell recognition and latent gene expression
      pattern in NPC, respectively. In conclusion, we showed that whole genome
      sequencing of EBV in NPC may facilitate discovery of previously unknown
      variations of pathogenic significance.

PMID- 22590639
TI  - Sodium chloride inhibits the growth and infective capacity of the amphibian
      chytrid fungus and increases host survival rates.
AB  - The amphibian chytrid fungus Batrachochytrium dendrobatidis is a recently emerged
      pathogen that causes the infectious disease chytridiomycosis and has been
      implicated as a contributing factor in the global amphibian decline. Since its
      discovery, research has been focused on developing various methods of mitigating
      the impact of chytridiomycosis on amphibian hosts but little attention has been
      given to the role of antifungal agents that could be added to the host's
      environment. Sodium chloride is a known antifungal agent used routinely in the
      aquaculture industry and this study investigates its potential for use as a
      disease management tool in amphibian conservation. The effect of 0-5 ppt NaCl on
      the growth, motility and survival of the chytrid fungus when grown in culture
      media and its effect on the growth, infection load and survivorship of infected
      Peron's tree frogs (Litoria peronii) in captivity, was investigated. The results
      reveal that these concentrations do not negatively affect the survival of the
      host or the pathogen. However, concentrations greater than 3 ppt significantly
      reduced the growth and motility of the chytrid fungus compared to 0 ppt.
      Concentrations of 1-4 ppt NaCl were also associated with significantly lower host
      infection loads while infected hosts exposed to 3 and 4 ppt NaCl were found to
      have significantly higher survival rates. These results support the potential for
      NaCl to be used as an environmentally distributed antifungal agent for the
      prevention of chytridiomycosis in susceptible amphibian hosts. However, further
      research is required to identify any negative effects of salt exposure on both
      target and non-target organisms prior to implementation.

PMID- 22590640
TI  - Formation of amyloid-like fibrils by Y-box binding protein 1 (YB-1) is mediated
      by its cold shock domain and modulated by disordered terminal domains.
AB  - YB-1, a multifunctional DNA- and RNA-binding nucleocytoplasmic protein, is
      involved in the majority of DNA- and mRNA-dependent events in the cell. It
      consists of three structurally different domains: its central cold shock domain
      has the structure of a beta-barrel, while the flanking domains are predicted to
      be intrinsically disordered. Recently, we showed that YB-1 is capable of forming
      elongated fibrils under high ionic strength conditions. Here we report that it is
      the cold shock domain that is responsible for formation of YB-1 fibrils, while
      the terminal domains differentially modulate this process depending on salt
      conditions. We demonstrate that YB-1 fibrils have amyloid-like features,
      including affinity for specific dyes and a typical X-ray diffraction pattern, and
      that in contrast to most of amyloids, they disassemble under nearly physiological
      conditions.

PMID- 22590641
TI  - Edwardsiella comparative phylogenomics reveal the new intra/inter-species
      taxonomic relationships, virulence evolution and niche adaptation mechanisms.
AB  - Edwardsiella bacteria are leading fish pathogens causing huge losses to
      aquaculture industries worldwide. E. tarda is a broad-host range pathogen that
      infects more than 20 species of fish and other animals including humans while E.
      ictaluri is host-adapted to channel catfish causing enteric septicemia of catfish
      (ESC). Thus, these two species consist of a useful comparative system for
      studying the intricacies of pathogen evolution. Here we present for the first
      time the phylogenomic comparisons of 8 genomes of E. tarda and E. ictaluri
      isolates. Genome-based phylogenetic analysis revealed that E. tarda could be
      separate into two kinds of genotypes (genotype I, EdwGI and genotype II, EdwGII)
      based on the sequence similarity. E. tarda strains of EdwGI were clustered
      together with the E. ictaluri lineage and showed low sequence conservation to E.
      tarda strains of EdwGII. Multilocus sequence analysis (MLSA) of 48 distinct
      Edwardsiella strains also supports the new taxonomic relationship of the
      lineages. We identified the type III and VI secretion systems (T3SS and T6SS) as
      well as iron scavenging related genes that fulfilled the criteria of a key
      evolutionary factor likely facilitating the virulence evolution and adaptation to
      a broad range of hosts in EdwGI E. tarda. The surface structure-related genes may
      underlie the adaptive evolution of E. ictaluri in the host specification
      processes. Virulence and competition assays of the null mutants of the
      representative genes experimentally confirmed their contributive roles in the
      evolution/niche adaptive processes. We also reconstructed the hypothetical
      evolutionary pathway to highlight the virulence evolution and niche adaptation
      mechanisms of Edwardsiella. This study may facilitate the development of
      diagnostics, vaccines, and therapeutics for this under-studied pathogen.

PMID- 22590642
TI  - PtdIns (3,4,5) P3 recruitment of Myo10 is essential for axon development.
AB  - Myosin X (Myo10) with pleckstrin homology (PH) domains is a motor protein acting
      in filopodium initiation and extension. However, its potential role has not been
      fully understood, especially in neuronal development. In the present study the
      preferential accumulation of Myo10 in axon tips has been revealed in primary
      culture of hippocampal neurons with the aid of immunofluorescence from anti-Myo10
      antibody in combination with anti-Tuj1 antibody as specific marker. Knocking down
      Myo10 gene transcription impaired outgrowth of axon with loss of Tau-1-positive
      phenotype. Interestingly, inhibition of actin polymerization by cytochalasin D
      rescued the defect of axon outgrowth. Furthermore, ectopic expression of Myo10
      with enhanced green fluorescence protein (EGFP) labeled Myo10 mutants induced
      multiple axon-like neurites in a motor-independent way. Mechanism studies
      demonstrated that the recruitment of Myo10 through its PH domain to
      phosphatidylinositol (3,4,5)-trisphosphate (PtdIns (3,4,5) P3) was essential for
      axon formation. In addition, in vivo studies confirmed that Myo10 was required
      for neuronal morphological transition during radial neuronal migration in the
      developmental neocortex.

PMID- 22590643
TI  - Educational inequalities in perinatal outcomes: the mediating effect of smoking
      and environmental tobacco exposure.
AB  - OBJECTIVE: Socioeconomic status (SES) is adversely associated with perinatal
      outcomes. This association is likely to be mediated by tobacco exposure. However,
      previous studies were limited to single perinatal outcomes and devoted no
      attention to environmental tobacco exposure. Therefore, this study aimed firstly
      to explain the role of maternal smoking in the association between maternal
      education and preterm birth (PTB), low birth weight (LBW) and small for
      gestational age (SGA), and secondly to explain whether environmental tobacco
      smoke mediates these associations further. STUDY DESIGN: This study was nested in
      a population-based cohort study in the Netherlands, the Amsterdam Born Children
      and their Development (ABCD) study. Analyses were done in a sample of 3821
      pregnant women of Dutch origin, using logistic regression analysis. RESULTS:
      Least educated women, who were more often smoking and exposed to environmental
      tobacco smoke, had a significantly higher risk of PTB (OR 1.95 [95% CI: 1.19
      3.20]), LBW (OR 2.41 [95% CI: 1.36-4.27]) and SGA (OR 1.90 [95% CI 1.32-2.74])
      than highly educated women. The mediating effect of smoking in the least educated
      women was 43% for PTB, 55% for LBW and 66% for SGA. Environmental tobacco smoke
      did not explain these associations further. After adjustment for maternal
      smoking, the association between lower maternal education and pregnancy outcomes
      was no longer significant. CONCLUSIONS: Smoking explains to a considerable extent
      the association between lower maternal education and adverse perinatal outcomes.
      Therefore, tobacco-interventions in lower educated women should be primarily
      focussed on maternal smoking to reduce PTB, LBW, and SGA. Additional attention to
      environmental tobacco exposure does not seem to reduce educational inequalities
      in perinatal outcomes.

PMID- 22590644
TI  - Human FOXN1-deficiency is associated with alphabeta double-negative and FoxP3+ T
      cell expansions that are distinctly modulated upon thymic transplantation.
AB  - Forkhead box N1 (FOXN1) is a transcription factor crucial for thymic epithelium
      development and prevention of its involution. Investigation of a patient with a
      rare homozygous FOXN1 mutation (R255X), leading to alopecia universalis and
      thymus aplasia, unexpectedly revealed non-maternal circulating T-cells, and,
      strikingly, large numbers of aberrant double-negative alphabeta T-cells
      (CD4negCD8neg, DN) and regulatory-like T-cells. These data raise the possibility
      that a thymic rudiment persisted, allowing T-cell development, albeit with
      disturbances in positive/negative selection, as suggested by DN and FoxP3+ cell
      expansions. Although regulatory-like T-cell numbers normalized following HLA
      mismatched thymic transplantation, the alphabetaDN subset persisted 5 years post
      transplantation. Involution of thymus allograft likely occurred 3 years post
      transplantation based on sj/betaTREC ratio, which estimates intrathymic precursor
      T-cell divisions and, consequently, thymic explant output. Nevertheless,
      functional immune-competence was sustained, providing new insights for the design
      of immunological reconstitution strategies based on thymic transplantation, with
      potential applications in other clinical settings.

PMID- 22590645
TI  - Diacylglycerol kinase beta knockout mice exhibit attention-deficit behavior and
      an abnormal response on methylphenidate-induced hyperactivity.
AB  - BACKGROUND: Diacylglycerol kinase (DGK) is an enzyme that phosphorylates
      diacylglycerol to produce phosphatidic acid. DGKbeta is one of the subtypes of
      the DGK family and regulates many intracellular signaling pathways in the central
      nervous system. Previously, we demonstrated that DGKbeta knockout (KO) mice
      showed various dysfunctions of higher brain function, such as cognitive
      impairment (with lower spine density), hyperactivity, reduced anxiety, and
      careless behavior. In the present study, we conducted further tests on DGKbeta KO
      mice in order to investigate the function of DGKbeta in the central nervous
      system, especially in the pathophysiology of attention deficit hyperactivity
      disorder (ADHD). METHODOLOGY/PRINCIPAL FINDINGS: DGKbeta KO mice showed attention
      deficit behavior in the object-based attention test and it was ameliorated by
      methylphenidate (MPH, 30 mg/kg, i.p.). In the open field test, DGKbeta KO mice
      displayed a decreased response to the locomotor stimulating effects of MPH (30
      mg/kg, i.p.), but showed a similar response to an N-methyl-d-aspartate (NMDA)
      receptor antagonist, MK-801 (0.3 mg/kg, i.p.), when compared to WT mice.
      Examination of the phosphorylation of extracellular signal-regulated kinase
      (ERK), which is involved in regulation of locomotor activity, indicated that
      ERK1/2 activation induced by MPH treatment was defective in the striatum of
      DGKbeta KO mice. CONCLUSIONS/SIGNIFICANCE: These findings suggest that DGKbeta KO
      mice showed attention-deficit and hyperactive phenotype, similar to ADHD.
      Furthermore, the hyporesponsiveness of DGKbeta KO mice to MPH was due to
      dysregulation of ERK phosphorylation, and that DGKbeta has a pivotal involvement
      in ERK regulation in the striatum.

PMID- 22590646
TI  - Hydrogen sulfide inhibits L-type calcium currents depending upon the protein
      sulfhydryl state in rat cardiomyocytes.
AB  - Hydrogen sulfide (H(2)S) is a novel gasotransmitter that inhibits L-type calcium
      currents (I (Ca, L)). However, the underlying molecular mechanisms are unclear.
      In particular, the targeting site in the L-type calcium channel where H(2)S
      functions remains unknown. The study was designed to investigate if the
      sulfhydryl group could be the possible targeting site in the L-type calcium
      channel in rat cardiomyocytes. Cardiac function was measured in isolated perfused
      rat hearts. The L-type calcium currents were recorded by using a whole cell
      voltage clamp technique on the isolated cardiomyocytes. The L-type calcium
      channel containing free sulfhydryl groups in H9C2 cells were measured by using
      Western blot. The results showed that sodium hydrosulfide (NaHS, an H(2)S donor)
      produced a negative inotropic effect on cardiac function, which could be partly
      inhibited by the oxidant sulfhydryl modifier diamide (DM). H(2)S donor inhibited
      the peak amplitude of I( Ca, L) in a concentration-dependent manner. However,
      dithiothreitol (DTT), a reducing sulfhydryl modifier markedly reversed the H(2)S
      donor-induced inhibition of I (Ca, L) in cardiomyocytes. In contrast, in the
      presence of DM, H(2)S donor could not alter cardiac function and L type calcium
      currents. After the isolated rat heart or the cardiomyocytes were treated with
      DTT, NaHS could markedly alter cardiac function and L-type calcium currents in
      cardiomyocytes. Furthermore, NaHS could decrease the functional free sulfhydryl
      group in the L-type Ca(2+) channel, which could be reversed by thiol reductant,
      either DTT or reduced glutathione. Therefore, our results suggest that H(2)S
      might inhibit L-type calcium currents depending on the sulfhydryl group in rat
      cardiomyocytes.

PMID- 22590647
TI  - Soluble epoxide hydrolase activity determines the severity of ischemia
      reperfusion injury in kidney.
AB  - Soluble epoxide hydrolase (sEH) in endothelial cells determines the plasma
      concentrations of epoxyeicosatrienoic acids (EETs), which may act as vasoactive
      agents to control vascular tone. We hypothesized that the regulation of sEH
      activity may have a therapeutic value in preventing acute kidney injury by
      controlling the concentration of EETs. In this study, we therefore induced
      ischemia-reperfusion injury (IRI) in C57BL/6 mice and controlled sEH activity by
      intraperitoneal administration of the sEH inhibitor 12-(3-adamantan-1-ylureido)
      dodecanoic acid (AUDA). The deterioration of kidney function induced by IRI was
      partially moderated and prevented by AUDA treatment. In addition, AUDA treatment
      significantly attenuated tubular necrosis induced by IRI. Ischemic injury induced
      the down-regulation of sEH, and AUDA administration had no effect on the
      expression pattern of sEH induced by IRI. In vivo sEH activity was assessed by
      measuring the substrate epoxyoctadecenoic acid (EpOME) and its metabolite
      dihydroxyoctadec-12-enoic acid (DHOME). Ischemic injury had no effects on the
      plasma concentrations of EpOME and DHOME, but inhibition of sEH by AUDA
      significantly increased plasma EpOME and the EpOME/DHOME ratio. The protective
      effect of the sEH inhibitor was achieved by suppression of proinflammatory
      cytokines and up-regulation of regulatory cytokines. AUDA treatment prevented the
      intrarenal infiltration of inflammatory cells, but promoted endothelial cell
      migration and neovascularization. The results of this study suggest that
      treatment with sEH inhibitors can reduce acute kidney injury.

PMID- 22590648
TI  - Distinct RGK GTPases differentially use alpha1- and auxiliary beta-binding
      dependent mechanisms to inhibit CaV1.2/CaV2.2 channels.
AB  - Ca(V)1/Ca(V)2 channels, comprised of pore-forming alpha(1) and auxiliary
      (beta,alpha(2)delta) subunits, control diverse biological responses in excitable
      cells. Molecules blocking Ca(V)1/Ca(V)2 channel currents (I(Ca)) profoundly
      regulate physiology and have many therapeutic applications. Rad/Rem/Rem2/Gem
      GTPases (RGKs) strongly inhibit Ca(V)1/Ca(V)2 channels. Understanding how RGKs
      block I(Ca) is critical for insights into their physiological function, and may
      provide design principles for developing novel Ca(V)1/Ca(V)2 channel inhibitors.
      The RGK binding sites within Ca(V)1/Ca(V)2 channel complexes responsible for
      I(Ca) inhibition are ambiguous, and it is unclear whether there are mechanistic
      differences among distinct RGKs. All RGKs bind beta subunits, but it is unknown
      if and how this interaction contributes to I(Ca) inhibition. We investigated the
      role of RGK/beta interaction in Rem inhibition of recombinant Ca(V)1.2 channels,
      using a mutated beta (beta(2aTM)) selectively lacking RGK binding. Rem blocked
      beta(2aTM)-reconstituted channels (74% inhibition) less potently than channels
      containing wild-type beta(2a) (96% inhibition), suggesting the prevalence of both
      beta-binding-dependent and independent modes of inhibition. Two mechanistic
      signatures of Rem inhibition of Ca(V)1.2 channels (decreased channel surface
      density and open probability), but not a third (reduced maximal gating charge),
      depended on Rem binding to beta. We identified a novel Rem binding site in
      Ca(V)1.2 alpha(1C) N-terminus that mediated beta-binding-independent inhibition.
      The Ca(V)2.2 alpha(1B) subunit lacks the Rem binding site in the N-terminus and
      displays a solely beta-binding-dependent form of channel inhibition. Finally, we
      discovered an unexpected functional dichotomy amongst distinct RGKs- while Rem
      and Rad use both beta-binding-dependent and independent mechanisms, Gem and Rem2
      use only a beta-binding-dependent method to inhibit Ca(V)1.2 channels. The
      results provide new mechanistic perspectives, and reveal unexpected variations in
      determinants, underlying inhibition of Ca(V)1.2/Ca(V)2.2 channels by distinct RGK
      GTPases.

PMID- 22590649
TI  - The role of low and high spatial frequencies in exogenous attention to
      biologically salient stimuli.
AB  - Exogenous attention can be understood as an adaptive tool that permits the
      detection and processing of biologically salient events even when the individual
      is engaged in a resource-consuming task. Indirect data suggest that the spatial
      frequency of stimulation may be a crucial element in this process. Behavioral and
      neural data (both functional and structural) were analyzed for 36 participants
      engaged in a digit categorization task in which distracters were presented.
      Distracters were biologically salient or anodyne images, and had three spatial
      frequency formats: intact, low spatial frequencies only, and high spatial
      frequencies only. Behavior confirmed enhanced exogenous attention to biologically
      salient distracters. The activity in the right and left intraparietal sulci and
      the right middle frontal gyrus was associated with this behavioral pattern and
      was greater in response to salient than to neutral distracters, the three areas
      presenting strong correlations to each other. Importantly, the enhanced response
      of this network to biologically salient distracters with respect to neutral
      distracters relied on low spatial frequencies to a significantly greater extent
      than on high spatial frequencies. Structural analyses suggested the involvement
      of internal capsule, superior longitudinal fasciculus and corpus callosum in this
      network. Results confirm that exogenous attention is preferentially captured by
      biologically salient information, and suggest that the architecture and function
      underlying this process are low spatial frequency-biased.

PMID- 22590650
TI  - Phosphorylation of nicastrin by SGK1 leads to its degradation through lysosomal
      and proteasomal pathways.
AB  - The gamma-secretase complex is involved in the intramembranous proteolysis of a
      variety of substrates, including the amyloid precursor protein and the Notch
      receptor. Nicastrin (NCT) is an essential component of the gamma-secretase
      complex and functions as a receptor for gamma-secretase substrates. In this
      study, we determined that serum- and glucocorticoid-induced protein kinase 1
      (SGK1) markedly reduced the protein stability of NCT. The SGK1 kinase activity
      was decisive for NCT degradation and endogenous SGK1 inhibited gamma-secretase
      activity. SGK1 downregulates NCT protein levels via proteasomal and lysosomal
      pathways. Furthermore, SGK1 directly bound to and phosphorylated NCT on Ser437,
      thereby promoting protein degradation. Collectively, our findings indicate that
      SGK1 is a gamma-secretase regulator presumably effective through phosphorylation
      and degradation of NCT.

PMID- 22590652
TI  - Irradiated male tsetse from a 40-year-old colony are still competitive in a
      Riparian forest in Burkina Faso.
AB  - BACKGROUND: Tsetse flies are the cyclical vectors of African trypanosomosis that
      constitute a major constraint to development in Africa. Their control is an
      important component of the integrated management of these diseases, and among the
      techniques available, the sterile insect technique (SIT) is the sole that is
      efficient at low densities. The government of Burkina Faso has embarked on a
      tsetse eradication programme in the framework of the PATTEC, where SIT is an
      important component. The project plans to use flies from a Glossina palpalis
      gambiensis colony that has been maintained for about 40 years at the Centre
      International de Recherche-Developpement sur l'Elevage en zone Subhumide
      (CIRDES). It was thus necessary to test the competitiveness of the sterile males
      originating from this colony. METHODOLOGY/PRINCIPAL FINDINGS: During the period
      January-February 2010, 16,000 sterile male G. p. gambiensis were released along a
      tributary of the Mouhoun river. The study revealed that with a mean sterile to
      wild male ratio of 1.16 (s.d. 0.38), the abortion rate of the wild female flies
      was significantly higher than before (p = 0.026) and after (p = 0.019) the
      release period. The estimated competitiveness of the sterile males (Fried index)
      was 0.07 (s.d. 0.02), indicating that a sterile to wild male ratio of 14.4 would
      be necessary to obtain nearly complete induced sterility in the female
      population. The aggregation patterns of sterile and wild male flies were similar.
      The survival rate of the released sterile male flies was similar to that observed
      in 1983-1985 for the same colony. CONCLUSIONS/SIGNIFICANCE: We conclude that
      gamma sterilised male G. p. gambiensis derived from the CIRDES colony have a
      competitiveness that is comparable to their competitiveness obtained 35 years ago
      and can still be used for an area-wide integrated pest management campaign with a
      sterile insect component in Burkina Faso.

PMID- 22590651
TI  - cGMP-phosphodiesterase inhibition enhances photic responses and synchronization
      of the biological circadian clock in rodents.
AB  - The master circadian clock in mammals is located in the hypothalamic
      suprachiasmatic nuclei (SCN) and is synchronized by several environmental
      stimuli, mainly the light-dark (LD) cycle. Light pulses in the late subjective
      night induce phase advances in locomotor circadian rhythms and the expression of
      clock genes (such as Per1-2). The mechanism responsible for light-induced phase
      advances involves the activation of guanylyl cyclase (GC), cGMP and its related
      protein kinase (PKG). Pharmacological manipulation of cGMP by phosphodiesterase
      (PDE) inhibition (e.g., sildenafil) increases low-intensity light-induced
      circadian responses, which could reflect the ability of the cGMP-dependent
      pathway to directly affect the photic sensitivity of the master circadian clock
      within the SCN. Indeed, sildenafil is also able to increase the phase-shifting
      effect of saturating (1200 lux) light pulses leading to phase advances of about 9
      hours, as well as in C57 a mouse strain that shows reduced phase advances. In
      addition, sildenafil was effective in both male and female hamsters, as well as
      after oral administration. Other PDE inhibitors (such as vardenafil and
      tadalafil) also increased light-induced phase advances of locomotor activity
      rhythms and accelerated reentrainment after a phase advance in the LD cycle.
      Pharmacological inhibition of the main downstream target of cGMP, PKG, blocked
      light-induced expression of Per1. Our results indicate that the cGMP-dependent
      pathway can directly modulate the light-induced expression of clock-genes within
      the SCN and the magnitude of light-induced phase advances of overt rhythms, and
      provide promising tools to design treatments for human circadian disruptions.

PMID- 22590654
TI  - Great genetic differentiation among populations of Meconopsis integrifolia and
      its implication for plant speciation in the Qinghai-Tibetan Plateau.
AB  - The complex tectonic events and climatic oscillations in the Qinghai-Tibetan
      Plateau (QTP), the largest and highest plateau in the world, are thought to have
      had great effects on the evolutionary history of the native plants. Of great
      interest is to investigate plant population genetic divergence in the QTP and its
      correlation with the geologic and climatic changes. We conducted a range-wide
      phylogeographical analysis of M. integrifolia based on the chloroplast DNA
      (cpDNA) trnL-trnF and trnfM-trnS regions, and defined 26 haplotypes that were
      phylogenetically divided into six clades dated to the late Tertiary. The six
      clades correspond, respectively, to highly differentiated population groups that
      do not overlap in geographic distribution, implying that the mountain ranges
      acting as corridors or barriers greatly affected the evolutionary history of the
      QTP plants. The older clade of M. integrifolia only occurs in the southwest of
      the species' range, whereas the distributions of younger clades extend
      northeastward in the eastern QTP, suggesting that climatic divergence resulting
      from the uplift of the QTP triggered the initial divergence of M. integrifolia
      native to the plateau. Also, the nrDNA ITS region was used to clarify the
      unexpected phylogenetic relationships of cpDNA haplotypes between M. integrifolia
      and M. betonicifolia. The topological incongruence between the two phylogenies
      suggests an ancestral hybridization between the two species. Our study indicates
      that geographic isolation and hybridization are two important mechanisms
      responsible for the population differentiation and speciation of Meconopsis, a
      species-rich genus with complex polyploids.

PMID- 22590653
TI  - Modification of cyclic NGR tumor neovasculature-homing motif sequence to human
      plasminogen kringle 5 improves inhibition of tumor growth.
AB  - BACKGROUND: Blood vessels in tumors express higher level of aminopeptidase N
      (APN) than normal tissues. Evidence suggests that the CNGRC motif is an APN
      ligand which targets tumor vasculature. Increased expression of APN in tumor
      vascular endothelium, therefore, offers an opportunity for targeted delivery of
      NGR peptide-linked drugs to tumors. METHODS/PRINCIPAL FINDINGS: To determine
      whether an additional cyclic CNGRC sequence could improve endothelial cell homing
      and antitumor effect, human plasminogen kringle 5 (hPK5) was modified genetically
      to introduce a CNGRC motif (NGR-hPK5) and was subsequently expressed in yeast.
      The biological activity of NGR-hPK5 was assessed and compared with that of wild
      type hPK5, in vitro and in vivo. NGR-hPK5 showed more potent antiangiogenic
      activity than wild-type hPK5: the former had a stronger inhibitory effect on
      proliferation, migration and cord formation of vascular endothelial cells, and
      produced a stronger antiangiogenic response in the CAM assay. To evaluate the
      tumor-targeting ability, both wild-type hPK5 and NGR-hPK5 were (99 m)Tc-labeled,
      for tracking biodistribution in the in vivo tumor model. By planar imaging and
      biodistribution analyses of major organs, NGR-hPK5 was found localized to tumor
      tissues at a higher level than wild-type hPK5 (approximately 3-fold). Finally,
      the effects of wild-type hPK5 and NGR-modified hPK5 on tumor growth were
      investigated in two tumor model systems. NGR modification improved tumor
      localization and, as a consequence, effectively inhibited the growth of mouse
      Lewis lung carcinoma (LLC) and human colorectal adenocarcinoma (Colo 205) cells
      in tumor-bearing mice. CONCLUSIONS/SIGNIFICANCE: These studies indicated that the
      addition of an APN targeting peptide NGR sequence could improve the ability of
      hPK5 to inhibit angiogenesis and tumor growth.

PMID- 22590655
TI  - Separation of allelopathy from resource competition using rice/barnyardgrass
      mixed-cultures.
AB  - Plant-plant interference is the combined effect of allelopathy, resource
      competition, and many other factors. Separating allelopathy from resource
      competition is almost impossible in natural systems but it is important to
      evaluate the relative contribution of each of the two mechanisms on plant
      interference. Research on allelopathy in natural and cultivated plant communities
      has been hindered in the absence of a reliable method that can separate
      allelopathic effect from resource competition. In this paper, the interactions
      between allelopathic rice accession PI312777, non-allelopathic rice accession
      Lemont and barnyardgrass were explored respectively by using a target (rice)
      neighbor (barnyardgrass) mixed-culture in hydroponic system. The relative
      competitive intensity (RCI), the relative neighbor effect (RNE) and the
      competitive ratio (CR) were used to quantify the intensity of competition between
      each of the two different potentially allelopathic rice accessions and
      barnyardgrass. Use of hydroponic culture system enabled us to exclude any
      uncontrolled factors that might operate in the soil and we were able to separate
      allelopathy from resource competition between each rice accession and
      barnyardgrass. The RCI and RNE values showed that the plant-plant interaction was
      positive (facilitation) for PI312777 but that was negative (competition) for
      Lemont and barnyardgrass in rice/barnyardgrass mixed-cultures. The CR values
      showed that one PI312777 plant was more competitive than 2 barnyardgrass plants.
      The allelopathic effects of PI312777 were much more intense than the resource
      competition in rice/barnyardgrass mixed cultures. The reverse was true for
      Lemont. These results demonstrate that the allelopathic effect of PI312777 was
      predominant in rice/barnyardgrass mixed-cultures. The most significant result of
      our study is the discovery of an experimental design, target-neighbor mixed
      culture in combination with competition indices, can successfully separate
      allelopathic effects from competition.

PMID- 22590657
TI  - High diversity of rabies viruses associated with insectivorous bats in Argentina:
      presence of several independent enzootics.
AB  - BACKGROUND: Rabies is a fatal infection of the central nervous system primarily
      transmitted by rabid animal bites. Rabies virus (RABV) circulates through two
      different epidemiological cycles: terrestrial and aerial, where dogs, foxes or
      skunks and bats, respectively, act as the most relevant reservoirs and/or
      vectors. It is widely accepted that insectivorous bats are not important vectors
      of RABV in Argentina despite the great diversity of bat species and the extensive
      Argentinean territory. METHODS: We studied the positivity rate of RABV detection
      in different areas of the country, and the antigenic and genetic diversity of 99
      rabies virus (RABV) strains obtained from 14 species of insectivorous bats
      collected in Argentina between 1991 and 2008. RESULTS: Based on the analysis of
      bats received for RABV analysis by the National Rabies system of surveillance,
      the positivity rate of RABV in insectivorous bats ranged from 3.1 to 5.4%,
      depending on the geographic location. The findings were distributed among an
      extensive area of the Argentinean territory. The 99 strains of insectivorous bat
      related sequences were divided into six distinct lineages associated with
      Tadarida brasiliensis, Myotis spp, Eptesicus spp, Histiotus montanus, Lasiurus
      blosseviilli and Lasiurus cinereus. Comparison with RABV sequences obtained from
      insectivorous bats of the Americas revealed co-circulation of similar genetic
      variants in several countries. Finally, inter-species transmission, mostly
      related with Lasiurus species, was demonstrated in 11.8% of the samples.
      CONCLUSIONS: This study demonstrates the presence of several independent
      enzootics of rabies in insectivorous bats of Argentina. This information is
      relevant to identify potential areas at risk for human and animal infection.

PMID- 22590656
TI  - Soil-transmitted helminth reinfection after drug treatment: a systematic review
      and meta-analysis.
AB  - BACKGROUND: Soil-transmitted helminth (STH) infections (i.e., Ascaris
      lumbricoides, hookworm, and Trichuris trichiura) affect more than a billion
      people. Preventive chemotherapy (i.e., repeated administration of anthelmintic
      drugs to at-risk populations), is the mainstay of control. This strategy,
      however, does not prevent reinfection. We performed a systematic review and meta
      analysis to assess patterns and dynamics of STH reinfection after drug treatment.
      METHODOLOGY: We systematically searched PubMed, ISI Web of Science, EMBASE,
      Cochrane Database of Systematic Reviews, China National Knowledge Infrastructure,
      WanFang Database, Chinese Scientific Journal Database, and Google Scholar.
      Information on study year, country, sample size, age of participants, diagnostic
      method, drug administration strategy, prevalence and intensity of infection pre-
      and posttreatment, cure and egg reduction rate, evaluation period posttreatment,
      and adherence was extracted. Pooled risk ratios from random-effects models were
      used to assess the risk of STH reinfection after treatment. Our protocol is
      available on PROSPERO, registration number: CRD42011001678. PRINCIPAL FINDINGS:
      From 154 studies identified, 51 were included and 24 provided STH infection rates
      pre- and posttreatment, whereas 42 reported determinants of predisposition to
      reinfection. At 3, 6, and 12 months posttreatment, A. lumbricoides prevalence
      reached 26% (95% confidence interval (CI): 16-43%), 68% (95% CI: 60-76%) and 94%
      (95% CI: 88-100%) of pretreatment levels, respectively. For T. trichiura,
      respective reinfection prevalence were 36% (95% CI: 28-47%), 67% (95% CI: 42
      100%), and 82% (95% CI: 62-100%), and for hookworm, 30% (95% CI: 26-34%), 55%
      (95% CI: 34-87%), and 57% (95% CI: 49-67%). Prevalence and intensity of
      reinfection were positively correlated with pretreatment infection status.
      CONCLUSION: STH reinfections occur rapidly after treatment, particularly for A.
      lumbricoides and T. trichiura. Hence, there is a need for frequent anthelmintic
      drug administrations to maximize the benefit of preventive chemotherapy.
      Integrated control approaches emphasizing health education and environmental
      sanitation are needed to interrupt transmission of STH.

PMID- 22590658
TI  - Dengue infection and miscarriage: a prospective case control study.
AB  - BACKGROUND: Dengue is the most prevalent mosquito borne infection worldwide.
      Vertical transmissions after maternal dengue infection to the fetus and pregnancy
      losses in relation to dengue illness have been reported. The relationship of
      dengue to miscarriage is not known. METHOD: We aimed to establish the
      relationship of recent dengue infection and miscarriage. Women who presented with
      miscarriage (up to 22 weeks gestation) to our hospital were approached to
      participate in the study. For each case of miscarriage, we recruited 3 controls
      with viable pregnancies at a similar gestation. A brief questionnaire on recent
      febrile illness and prior dengue infection was answered. Blood was drawn from
      participants, processed and the frozen serum was stored. Stored sera were thawed
      and then tested in batches with dengue specific IgM capture ELISA, dengue non
      structural protein 1 (NS1) antigen and dengue specific IgG ELISA tests. Controls
      remained in the analysis if their pregnancies continued beyond 22 weeks
      gestation. Tests were run on 116 case and 341 control sera. One case (a
      misdiagnosed viable early pregnancy) plus 45 controls (39 lost to follow up and
      six subsequent late miscarriages) were excluded from analysis. FINDINGS: Dengue
      specific IgM or dengue NS1 antigen (indicating recent dengue infection) was
      positive in 6/115 (5.2%) cases and 5/296 (1.7%) controls RR 3.1 (95% CI 1.0-10) P
      = 0.047. Maternal age, gestational age, parity and ethnicity were dissimilar
      between cases and controls. After adjustments for these factors, recent dengue
      infection remained significantly more frequently detected in cases than controls
      (AOR 4.2 95% CI 1.2-14 P = 0.023). INTERPRETATION: Recent dengue infections were
      more frequently detected in women presenting with miscarriage than in controls
      whose pregnancies were viable. After adjustments for confounders, the positive
      association remained.

PMID- 22590659
TI  - Proteomic analysis of the cyst stage of Entamoeba histolytica.
AB  - BACKGROUND: The category B agent of bioterrorism, Entamoeba histolytica has a two
      stage life cycle: an infective cyst stage, and an invasive trophozoite stage. Due
      to our inability to effectively induce encystation in vitro, our knowledge about
      the cyst form remains limited. This also hampers our ability to develop cyst
      specific diagnostic tools. AIMS: Three main aims were (i) to identify E.
      histolytica proteins in cyst samples, (ii) to enrich our knowledge about the cyst
      stage, and (iii) to identify candidate proteins to develop cyst-specific
      diagnostic tools. METHODS: Cysts were purified from the stool of infected
      individuals using Percoll (gradient) purification. A highly sensitive LC-MS/MS
      mass spectrometer (Orbitrap) was used to identify cyst proteins. RESULTS: A total
      of 417 non-redundant E. histolytica proteins were identified including 195
      proteins that were never detected in trophozoite-derived proteomes or expressed
      sequence tag (EST) datasets, consistent with cyst specificity. Cyst-wall specific
      glycoproteins Jacob, Jessie and chitinase were positively identified. Antibodies
      produced against Jacob identified cysts in fecal specimens and have potential
      utility as a diagnostic reagent. Several protein kinases, small GTPase signaling
      molecules, DNA repair proteins, epigenetic regulators, and surface associated
      proteins were also identified. Proteins we identified are likely to be among the
      most abundant in excreted cysts, and therefore show promise as diagnostic
      targets. MAJOR CONCLUSIONS: The proteome data generated here are a first for
      naturally-occurring E. histolytica cysts, and they provide important insights
      into the infectious cyst form. Additionally, numerous unique candidate proteins
      were identified which will aid the development of new diagnostic tools for
      identification of E. histolytica cysts.

PMID- 22590660
TI  - Inducible nitric oxide synthase in heart tissue and nitric oxide in serum of
      Trypanosoma cruzi-infected rhesus monkeys: association with heart injury.
AB  - BACKGROUND: The factors contributing to chronic Chagas' heart disease remain
      unknown. High nitric oxide (NO) levels have been shown to be associated with
      cardiomyopathy severity in patients. Further, NO produced via inducible nitric
      oxide synthase (iNOS/NOS2) is proposed to play a role in Trypanosoma cruzi
      control. However, the participation of iNOS/NOS2 and NO in T. cruzi control and
      heart injury has been questioned. Here, using chronically infected rhesus monkeys
      and iNOS/NOS2-deficient (Nos2(-/-)) mice we explored the participation of
      iNOS/NOS2-derived NO in heart injury in T. cruzi infection. METHODOLOGY: Rhesus
      monkeys and C57BL/6 and Nos2(-/-) mice were infected with the Colombian T. cruzi
      strain. Parasite DNA was detected by polymerase chain reaction, T. cruzi antigens
      and iNOS/NOS2(+) cells were immunohistochemically detected in heart sections and
      NO levels in serum were determined by Griess reagent. Heart injury was assessed
      by electrocardiogram (ECG), echocardiogram (ECHO), creatine kinase heart
      isoenzyme (CK-MB) activity levels in serum and connexin 43 (Cx43) expression in
      the cardiac tissue. RESULTS: Chronically infected monkeys presented conduction
      abnormalities, cardiac inflammation and fibrosis, which resembled the spectrum of
      human chronic chagasic cardiomyopathy (CCC). Importantly, chronic myocarditis was
      associated with parasite persistence. Moreover, Cx43 loss and increased CK-MB
      activity levels were primarily correlated with iNOS/NOS2(+) cells infiltrating
      the cardiac tissue and NO levels in serum. Studies in Nos2(-/-) mice reinforced
      that the iNOS/NOS2-NO pathway plays a pivotal role in T. cruzi-elicited
      cardiomyocyte injury and in conduction abnormalities that were associated with
      Cx43 loss in the cardiac tissue. CONCLUSION: T. cruzi-infected rhesus monkeys
      reproduce features of CCC. Moreover, our data support that in T. cruzi infection
      persistent parasite-triggered iNOS/NOS2 in the cardiac tissue and NO
      overproduction might contribute to CCC severity, mainly disturbing of the
      molecular pathway involved in electrical synchrony. These findings open a new
      avenue for therapeutic tools in Chagas' heart disease.

PMID- 22590661
TI  - Interval routine appendectomy following conservative treatment of acute
      appendicitis: Is it really needed.
AB  - Conservative management of acute appendicitis (AA) is gradually being adopted as
      a valuable therapeutic choice in the treatment of selected patients with AA. This
      approach is based on the results of many recent studies indicating that it is a
      valuable and effective alternative to routine emergency appendectomy. Existing
      data do not support routine interval appendectomy following successful
      conservative management of AA; indeed, the risk of recurrence is low. Moreover,
      recurrences usually exhibit a milder clinical course compared to the first
      episode of AA. The role of routine interval appendectomy is also questioned
      recently, even in patients with AA complicated by plastron or localized abscess
      formation. Surgical judgment is required to avoid misdiagnosis when selecting a
      conservative approach in patients with a presumed "appendiceal" mass.

PMID- 22590662
TI  - Malignant ascites: A review of prognostic factors, pathophysiology and
      therapeutic measures.
AB  - Malignant ascites indicates the presence of malignant cells in the peritoneal
      cavity and is a grave prognostic sign. While survival in this patient population
      is poor, averaging about 20 wk from time of diagnosis, quality of life can be
      improved through palliative procedures. Selecting the appropriate treatment
      modality remains a careful process, which should take into account potential
      risks and benefits and the life expectancy of the patient. Traditional therapies,
      including paracentesis, peritoneovenous shunt placement and diuretics, are
      successful and effective in varying degrees. After careful review of the
      patient's primary tumor origin, tumor biology, tumor stage, patient performance
      status and comorbidities, surgical debulking and intraperitoneal chemotherapy
      should be considered if the benefit of therapy outweighs the risk of operation
      because survival curves can be extended and palliation of symptomatic malignant
      ascites can be achieved in select patients. In patients with peritoneal
      carcinomatosis who do not qualify for surgical cytoreduction but suffer from the
      effects of malignant ascites, intraperitoneal chemotherapy can be safely and
      effectively administered via laparoscopic techniques. Short operative times,
      short hospital stays, low complication rates and ultimately symptomatic relief
      are the advantages of laparoscopically administering heated intraperitoneal
      chemotherapy, making it not only a valuable treatment modality but also the most
      successful treatment modality for achieving palliative cure of malignant ascites.

PMID- 22590663
TI  - Resection and reconstruction of the inferior vena cava for neoplasms.
AB  - AIM: To evaluate the results of an aggressive surgical approach of resection and
      reconstruction of the inferior vena cava (IVC). METHODS: The approach to caval
      resection depends on the extent and location of tumor involvement. The supra- and
      infra-hepatic portion of the IVC was dissected and taped. Left and right renal
      veins were also taped to control the bleeding. In 12 of the cases with partial
      tangential resection of the IVC, the flow was reduced to less than 40% so that
      the vein was primarily closed with a running suture. In 3 of the cases, the lumen
      of the vein was significantly reduced, requiring the use of a
      polytetrafluoroethylene (PTFE) patch. In 2 of the cases with segmental resection
      of the IVC, a PTFE prosthesis was used and in 1 case, the IVC was resected
      without reconstruction due to shunting the blood through the azygos and
      hemiazygos veins. RESULTS: The mean operation time was 266 min (230-310 min) with
      an average intraoperative blood loss of 300 mL (200-2000 mL). The patients stayed
      in intensive care unit for 1.8 d (1-3 d). Mean hospital stay was 9 d (7-15 d).
      Twelve patients (66.7%) had no complications and 6 patients (33.3%) had the
      following complications: acute bleeding in 2 patients; bile leak in 2 patients;
      intra abdominal abscess in 1 patient; pulmonary embolism in 2 patients; and
      partial thrombosis of the patch in 1 patient. General complications such as
      pneumonia, pleural effusion and cardiac arrest were observed in the same group of
      patients. In all but 1 case, the complications were transient and successfully
      controlled. The mortality rate was 11.1% (n = 2). One patient died due to cardiac
      arrest and pulmonary embolism in the operation room and the second one died 2 d
      after surgery due to coagulopathy. With a median follow-up of 24 mo, 5 (27.8%)
      patients died of tumor recurrence and 11 (61.1%) are still alive, but three of
      them have a recurrence on computed tomography. CONCLUSION: There are a variety of
      options for reconstruction after resection of the IVC that offers a higher
      resectable rate and better prognosis in selected cases.

PMID- 22590664
TI  - Lymphoma presenting as a necrotic colonic mass.
AB  - Primary colonic lymphomas represent a rare minority among the colonic neoplasms.
      Their correct pre-operative identification is crucial for the design of
      treatment. We herein describe a case of a colonic lymphoma presenting as a
      necrotic colonic mass and we discuss the current evidence about the presentation,
      diagnosis and treatment of lymphomas isolated to the colon.

PMID- 22590665
TI  - TNM staging update for lung cancer: Why is this important?
AB  - Cancer staging characterises the extent of disease facilitating selection of the
      most appropriate management and therapy and providing prediction of prognosis. As
      understanding of lung cancer evolves the opportunities arises to adjust disease
      staging. The adoption of the 7th edition tumour, node, metastasis staging system
      should result in improved treatment selection and more accurate prognostic
      information for the individual patient.

PMID- 22590666
TI  - The 7th lung cancer TNM classification and staging system: Review of the changes
      and implications.
AB  - Lung cancer is the most common cause of death from cancer in males, accounting
      for more than 1.4 million deaths in 2008. It is a growing concern in China, Asia
      and Africa as well. Accurate staging of the disease is an important part of the
      management as it provides estimation of patient's prognosis and identifies
      treatment sterategies. It also helps to build a database for future staging
      projects. A major revision of lung cancer staging has been announced with effect
      from January 2010. The new classification is based on a larger surgical and non
      surgical cohort of patients, and thus more accurate in terms of outcome
      prediction compared to the previous classification. There are several original
      papers regarding this new classification which give comprehensive description of
      the methodology, the changes in the staging and the statistical analysis. This
      overview is a simplified description of the changes in the new classification and
      their potential impact on patients' treatment and prognosis.

PMID- 22590667
TI  - Reliable clinical and sonographic findings in the diagnosis of abdominal wall
      endometriosis near cesarean section scar.
AB  - AIM: To highlight sonographic and clinical characteristics of scar endometrioma
      with special emphasis on size-related features. METHODS: Thirty women (mean age
      30.6 years, range 20-42 years) with 33 scar endometriomas (mean diameter 27.1 mm,
      range 7-60 mm) were consecutively studied by Sonography and Color Doppler
      examination prior to surgery. Pathological examination was available in all
      cases. RESULTS: The most frequent (24 of 33 nodules, 74%) sonographic B-mode
      aspect of endometrioma was that of an inhomogenously hypoechoic roundish nodule
      with fibrotic changes (in the form of hyperechoic spots or strands), a peripheral
      inflammatory hyperechoic ring, spiculated margins and a single vascular pedicle
      entering the mass at the periphery. On average, 1.6 cesarean sections were
      recorded per patient (range 1-3). The median interval between the last cesarean
      section and admission to hospital was 36 mo (range 12-120 mo) and the median
      duration of symptoms before admission was 25.7 mo (range 0.5-80 mo). 13 patients
      had 13 large endometriomas (>= 30 mm) with a mean lesion diameter of 41.3 +/-
      9.02 mm (range 30-60 mm). Seventeen women had 20 small endometriomas with a mean
      lesion size of 18.2 +/- 5.17 mm (range 7-26 mm). The mean interval between the
      last cesarean section and admission to hospital (66.0 mo vs 39.6 mo, P < 0.01)
      and the mean duration of symptoms before admission (43.0 mo vs 17.4 mo, P < 0.01)
      were significantly longer in patients with large endometriomas; in addition, a
      statistically significant higher percentage of patients with large implants had
      undergone previous inconclusive diagnostic examinations, including either
      computed tomography/magnetic resonance imaging/fine needle biopsy/laparoscopy
      (38.4% vs 0%, P < 0.05). On sonography, large endometriomas showed frequent
      cystic portions and fistulous tracts (P < 0.02), loss of round/oval shape (P <
      0.04) along with increased vascularity (P < 0.04). CONCLUSION: Endometrioma near
      cesarean section scar is an often neglected disease, but knowledge of its
      clinical and sonographic findings may prevent a delay in diagnosis that typically
      occurs in patients with larger (>= 3 cm) endometriomas.

PMID- 22590668
TI  - Chest radiographic and computed tomographic manifestations in allergic
      bronchopulmonary aspergillosis.
AB  - AIM: To investigate the chest radiographic and high resolution computed
      tomography (HRCT) chest manifestations in glucocorticoid-naive allergic
      bronchopulmonary aspergillosis (ABPA) patients. METHODS: This is a prospective
      observational study and includes 60 consecutive glucocorticoid-naive patients
      with ABPA who underwent chest radiography and HRCT of the chest (1.25 mm every 10
      mm) in the routine diagnostic workup for ABPA. RESULTS: Chest radiographs were
      normal in 50% of cases. Of the remainder, most patients demonstrated permanent
      findings in the form of parallel line and ring shadows suggesting bronchiectasis.
      Consolidation was detected in 17 cases but in the majority, the corresponding
      HRCT chest scan showed mucus-filled bronchiectatic cavities. Chest HRCT was
      normal in 22 patients, while central bronchiectasis (CB) was demonstrated in the
      remaining 38 patients. Bronchiectasis extended to the periphery in 33%-43%
      depending on the criteria used for defining CB. The other findings observed on
      HRCT were mucoid impaction, centrilobular nodules and high-attenuation mucus in
      decreasing order of frequency. CONCLUSION: Patients with ABPA can present with
      normal HRCT chest scans. Central bronchiectasis cannot be considered a
      characteristic feature of ABPA as peripheral bronchiectasis is commonly observed.
      Consolidation is an uncommon finding in ABPA.

PMID- 22590669
TI  - Primary malignant fibrous histiocytoma of the abdominal cavity: CT findings and
      pathological correlation.
AB  - AIM: To study computed tomography (CT) features of abdominal malignant fibrous
      histiocytoma (MFH) in various rare locations. METHODS: We retroprospectively
      identified cases of MFH involving the abdominal cavity. Particular attention was
      paid to details regarding imaging features and histological types. RESULTS: The
      study population consisted of seven men and one woman, with a mean age of 52.5
      years. Seven patients had some physical symptoms, while one was incidentally
      detected. The sites of origin were liver (n = 3), greater omentum (n = 1),
      superior mesentery (n = 1), ileum (n = 1), right psoas muscle (n = 1) and right
      kidney (n = 1). With the exception of the ileum lesion, all were of huge size.
      The contour of the lesions was more or less clear. Foci of necrosis were present
      in six lesions (n = 6). On plain CT scan, all lesions were hypo to iso dense. The
      lesion in the greater omentum was cystic. One lesion (n = 1) showed significant
      enhancement and the cystic lesion showed mild peripheral enhancement. An
      abundance of blood vessels surrounding the mass was seen in two lesions (n = 2)
      and both were of the inflammatory variety. Pathological examination revealed
      storiform-pleomorphic variety (n = 4), inflammatory variety (n = 3) and myxoid
      variety (n = 1). Two of the patients with inflammatory MFH had a clinical
      presentation of fever and one was afebrile, however, blood investigations in all
      three showed leukocytosis. CONCLUSION: Primary MFHs of the abdominal viscera and
      gastrointestinal tract are generally huge soft tissue masses containing areas of
      low attenuation and mild to moderate contrast enhancement.

PMID- 22590670
TI  - Multimodal morphometry and functional magnetic resonance imaging in schizophrenia
      and auditory hallucinations.
AB  - AIM: To validate a multimodal [structural and functional magnetic resonance (MR)]
      approach as coincidence brain clusters are hypothesized to correlate with
      clinical severity of auditory hallucinations. METHODS: Twenty-two patients
      meeting Diagnostic and Statistical Manual of Mental Disorders (fourth edition,
      DSM-IV) criteria for schizophrenia and experiencing persistent hallucinations
      together with 28 healthy controls were evaluated with structural and functional
      MR imaging with an auditory paradigm designed to replicate those emotions related
      to the patients' hallucinatory experiences. Coincidence maps were obtained by
      combining structural maps of gray matter reduction with emotional functional
      increased activation. Abnormal areas were correlated with the brief psychiatric
      rating scale (BPRS) and the psychotic symptom rating scale (PSYRATS) scales.
      RESULTS: The coincidence analysis showed areas with coexistence gray matter
      reductions and emotional activation in bilateral middle temporal and superior
      temporal gyri. Significant negative correlations between BPRS and PSYRATS scales
      were observed. BPRS scores were negatively correlated in the middle temporal
      gyrus (right) (t = 6.86, P = 0.001), while negative PSYRATS correlation affected
      regions in both the superior temporal gyrus (left) (t = 7.85, P = 0.001) and
      middle temporal gyrus (left) (t = 4.97, P = 0.002). CONCLUSION: Our data identify
      left superior and middle temporal gyri as relevant areas for the understanding of
      auditory hallucinations in schizophrenia. The use of multimodal approaches,
      sharing structural and functional information, may demonstrate areas specifically
      linked to the severity of auditory hallucinations.

PMID- 22590671
TI  - Virtual nonenhanced abdominal dual-energy MDCT: Analysis of image
      characteristics.
AB  - AIM: To evaluate abdominal and pelvic image characteristics and artifacts on
      virtual nonenhanced (VNE) images generated from contrast-enhanced dual-energy
      multidetector computed tomography (MDCT) studies. METHODS: Hadassah-Hebrew
      University Medical Institutional Review Board approval was obtained; 22 patients
      underwent clinically-indicated abdominal and pelvic single-source dual-energy
      MDCT (Philips Healthcare, Cleveland, OH, USA), pre- and post-IV administration of
      Omnipaque 300 contrast (100 cc). Various solid and vascular structures were
      evaluated. VNE images were generated from the portal contrast-enhanced phase
      using probabilistic separation. Contrast-enhanced-, regular nonenhanced (RNE)-,
      and VNE images were evaluated with a total of 1494 density measurements. The
      ratio of iodine contrast deletion was calculated. Visualization of
      calcifications, urinary tract stones, and image artifacts in VNE images were
      assessed. RESULTS: VNE images were successfully generated in all patients.
      Significant portal-phase iodine contrast deletion was seen in the kidney (61.7%),
      adrenal gland (55.3%), iliac artery (55.0%), aorta (51.6%), and spleen (34.5%).
      Contrast deletion was also significant in the right atrium (RA) (51.5%) and
      portal vein (39.3%), but insignificant in the iliac vein and inferior vena cava
      (IVC). Average post contrast-to-VNE HU differences were significant (P < 0.05) in
      the: RA -135.3 (SD 121.8), aorta -114.1 (SD 48.5), iliac artery -104.6 (SD 53.7),
      kidney -30.3 (SD 34.9), spleen -9.2 (SD 8.8), and portal vein -7.7 (SD 13.2).
      Average VNE-to-RNE HU differences were significant in all organs but the prostate
      and subcutaneous fat: aorta 38.0 (SD 9.3), RA 37.8 (SD 16.1), portal vein 21.8
      (SD 12.0), IVC 12.2 (SD 11.6), muscle 3.3 (SD 4.9), liver 5.7 (SD 6.4), spleen
      22.3 (SD 9.8), kidney 40.5 (SD 6.8), and adrenal 20.7 (SD 13.5). On VNE images,
      196/213 calcifications (92%) and 5/6 renal stones (84%) were visualized. Lytic
      like artifacts in the vertebral bodies were seen in all studies. CONCLUSION:
      Iodine deletion in VNE images is most significant in arteries, and less
      significant in solid organs and veins. Most vascular and intra-abdominal organ
      calcifications are preserved.

PMID- 22590672
TI  - ARFI elastography for the evaluation of diffuse thyroid gland pathology:
      Preliminary results.
AB  - AIM: To assess whether acoustic radiation force impulse (ARFI) elastography can
      differentiate normal from pathological thyroid parenchyma. METHODS: We evaluated
      136 subjects (mean age 45.8 +/- 15.6 years, 106 women and 30 men): 44 (32.3%)
      without thyroid pathology, 48 (35.3%) with Basedow-Graves' disease (GD), 37
      (27.2%) with chronic autoimmune thyroiditis (CAT; diagnosed by specific tests), 4
      (2.9%) with diffuse thyroid goiter and 3 (2.2%) cases with thyroid pathology
      induced by amiodarone. In all patients, 10 elastographic measurements were made
      in the right thyroid lobe and 10 in the left thyroid lobe, using a 1-4.5 MHZ
      convex probe and a 4-9 MHz linear probe, respectively. Median values were
      calculated for thyroid stiffness and expressed in meters/second (m/s). RESULTS:
      Thyroid stiffness (TS) assessed by means of ARFI in healthy subjects (2 +/- 0.40
      m/s) was significantly lower than in GD (2.67 +/- 0.53 m/s) (P < 0.0001) and CAT
      patients (2.43 +/- 0.58 m/s) (P = 0.0002), but the differences were not
      significant between GD vs CAT patients (P = 0.053). The optimal cut-off value for
      the prediction of diffuse thyroid pathology was 2.36 m/s. For this cut-off value,
      TS had 62.5% sensitivity, 79.5% specificity, 87.6% predictive positive value,
      55.5% negative predictive value and 72.7% accuracy for the presence of diffuse
      thyroid gland pathology (AUROC = 0.804). There were no significant differences
      between the TS values obtained with linear vs convex probes and when 5 vs 10
      measurements were taken in each lobe (median values). CONCLUSION: ARFI seems to
      be a useful method for the assessment of diffuse thyroid gland pathology.

PMID- 22590673
TI  - Quantitative measurement of contrast enhancement of esophageal squamous cell
      carcinoma on clinical MDCT.
AB  - AIM: To investigate contrast-enhanced computed tomography (CECT) for
      discriminating esophageal squamous cell carcinoma (ESCC) from normal esophagus
      and evaluating outcomes within tumors after chemoradiotherapy (CRT). METHODS:
      Sixty-four patients with surgical ESCC served as group A, and underwent thoracic
      contrast-enhanced scan with 16-section multidetector row CT 1 wk before surgery.
      Thirty-five patients with advanced ESCC receiving 4-wk CRT and showing response
      to CRT served as group B, and underwent CT scans similar with group A 4 wk after
      completion of CRT. In group A, differences in CT attenuation values (in HU)
      between the preoperative ESCC and background normal esophageal wall (delta
      CT(1)), or between different background normal esophageal walls (delta CT(2))
      were compared. Furthermore, delta CT(1) between group A and B was also compared.
      RESULTS: In group A, mean delta CT(1) was higher than delta CT(2) (23.86 +/-
      10.59 HU vs 6.24 +/- 3.06 HU, P < 0.05). When a delta CT(1) of 10.025 HU was
      employed at a cut-off value to discriminate ESCC from normal esophagus, a
      sensitivity of 89.1% and specificity of 90.6% were achieved. Mean delta CT(1) was
      lower in group B than in group A (9.25 +/- 10.86 vs 23.86 +/- 10.59, P < 0.05),
      and a delta CT(1) of 15.45 HU was obtained at a cut-off value to assess the CRT
      changes with a sensitivity of 76.6% and specificity of 77.1%. CONCLUSION: CECT
      might be a clinical technique for discriminating ESCC from normal esophagus, and
      evaluating outcome in the tumors treated with CRT.

PMID- 22590675
TI  - Mining the protein data bank to differentiate error from structural variation in
      clustered static structures: an examination of HIV protease.
AB  - The Protein Data Bank (PDB) contains over 71,000 structures. Extensively studied
      proteins have hundreds of submissions available, including mutations, different
      complexes, and space groups, allowing for application of data-mining algorithms
      to analyze an array of static structures and gain insight about a protein's
      structural variation and possibly its dynamics. This investigation is a case
      study of HIV protease (PR) using in-house algorithms for data mining and
      structure superposition through generalized formulae that account for multiple
      conformations and fractional occupancies. Temperature factors (B-factors) are
      compared with spatial displacement from the mean structure over the entire study
      set and separately over bound and ligand-free structures, to assess the
      significance of structural deviation in a statistical context. Space group
      differences are also examined.

PMID- 22590674
TI  - Nuclear actin and lamins in viral infections.
AB  - Lamins are the best characterized cytoskeletal components of the cell nucleus
      that help to maintain the nuclear shape and participate in diverse nuclear
      processes including replication or transcription. Nuclear actin is now widely
      accepted to be another cytoskeletal protein present in the nucleus that fulfills
      important functions in the gene expression. Some viruses replicating in the
      nucleus evolved the ability to interact with and probably utilize nuclear actin
      for their replication, e.g., for the assembly and transport of capsids or mRNA
      export. On the other hand, lamins play a role in the propagation of other viruses
      since nuclear lamina may represent a barrier for virions entering or escaping the
      nucleus. This review will summarize the current knowledge about the roles of
      nuclear actin and lamins in viral infections.

PMID- 22590676
TI  - The coronavirus E protein: assembly and beyond.
AB  - The coronavirus E protein is a small membrane protein that has an important role
      in the assembly of virions. Recent studies have indicated that the E protein has
      functions during infection beyond assembly, including in virus egress and in the
      host stress response. Additionally, the E protein has ion channel activity,
      interacts with host proteins, and may have multiple membrane topologies. The goal
      of this review is to highlight the properties and functions of the E protein, and
      speculate on how they may be related.

PMID- 22590677
TI  - Feline immunodeficiency virus in South America.
AB  - The rapid emergence of AIDS in humans during the period between 1980 and 2000 has
      led to extensive efforts to understand more fully similar etiologic agents of
      chronic and progressive acquired immunodeficiency disease in several mammalian
      species. Lentiviruses that have gene sequence homology with human
      immunodeficiency virus (HIV) have been found in different species (including
      sheep, goats, horses, cattle, cats, and several Old World monkey species).
      Lentiviruses, comprising a genus of the Retroviridae family, cause persistent
      infection that can lead to varying degrees of morbidity and mortality depending
      on the virus and the host species involved. Feline immunodeficiency virus (FIV)
      causes an immune system disease in domestic cats (Felis catus) involving
      depletion of the CD4+ population of T lymphocytes, increased susceptibility to
      opportunistic infections, and sometimes death. Viruses related to domestic cat
      FIV occur also in a variety of nondomestic felids. This is a brief overview of
      the current state of knowledge of this large and ancient group of viruses (FIVs)
      in South America.

PMID- 22590678
TI  - Innate immunity evasion by Dengue virus.
AB  - For viruses to productively infect their hosts, they must evade or inhibit
      important elements of the innate immune system, namely the type I interferon
      (IFN) response, which negatively influences the subsequent development of antigen
      specific adaptive immunity against those viruses. Dengue virus (DENV) can inhibit
      both type I IFN production and signaling in susceptible human cells, including
      dendritic cells (DCs). The NS2B3 protease complex of DENV functions as an
      antagonist of type I IFN production, and its proteolytic activity is necessary
      for this function. DENV also encodes proteins that antagonize type I IFN
      signaling, including NS2A, NS4A, NS4B and NS5 by targeting different components
      of this signaling pathway, such as STATs. Importantly, the ability of the NS5
      protein to bind and degrade STAT2 contributes to the limited host tropism of DENV
      to humans and non-human primates. In this review, we will evaluate the
      contribution of innate immunity evasion by DENV to the pathogenesis and host
      tropism of this virus.

PMID- 22590679
TI  - Folding and oligomerization of the gp2b/gp3/gp4 spike proteins of equine
      arteritis virus in vitro.
AB  - Equine arteritis virus (EAV) is a small, positive-stranded RNA virus. The
      glycoproteins gp2b, gp3 and gp4 form a heterotrimer in the viral envelope, which
      is required for cell entry of EAV. We describe expression of the ectodomains of
      the proteins in E. coli and their refolding from inclusion bodies. After
      extraction of inclusion bodies and dialysis, Gst-, but not His-tagged proteins,
      refold into a soluble conformation. However, when dialyzed together with Gst-gp3
      or with Gst-gp4, His-gp2b and His-gp4 remain soluble and oligomers are obtained
      by affinity-chromatography. Thus, folding and oligomerization of gp2b, gp3 and
      gp4 in vitro are interdependent processes.

PMID- 22590680
TI  - Interplay between interferon-mediated innate immunity and porcine reproductive
      and respiratory syndrome virus.
AB  - Innate immunity is the first line of defense against viral infection, and in
      turn, viruses have evolved to evade host immune surveillance. As a result,
      viruses may persist in host and develop chronic infections. Type I interferons
      (IFN-alpha/beta) are among the most potent antiviral cytokines triggered by viral
      infections. Porcine reproductive and respiratory syndrome (PRRS) is a disease of
      pigs that is characterized by negligible induction of type I IFNs and viral
      persistence for an extended period. For IFN production, RIG-I/MDA5 and JAK-STAT
      pathways are two major signaling pathways, and recent studies indicate that PRRS
      virus is armed to modulate type I IFN responses during infection. This review
      describes the viral strategies for modulation of type I IFN responses. At least
      three non-structural proteins (Nsp1, Nsp2, and Nsp11) and a structural protein (N
      nucleocapsid protein) have been identified and characterized to play roles in the
      IFN suppression and NF-kappaB pathways. Nsp's are early proteins while N is a
      late protein, suggesting that additional signaling pathways may be involved in
      addition to the IFN pathway. The understanding of molecular bases for virus
      mediated modulation of host innate immune signaling will help us design new
      generation vaccines and control PRRS.

PMID- 22590681
TI  - Structural basis for differential neutralization of ebolaviruses.
AB  - There are five antigenically distinct ebolaviruses that cause hemorrhagic fever
      in humans or non-human primates (Ebola virus, Sudan virus, Reston virus, Tai
      Forest virus, and Bundibugyo virus). The small handful of antibodies known to
      neutralize the ebolaviruses bind to the surface glycoprotein termed GP1,2.
      Curiously, some antibodies against them are known to neutralize in vitro but not
      protect in vivo, whereas other antibodies are known to protect animal models in
      vivo, but not neutralize in vitro. A detailed understanding of what constitutes a
      neutralizing and/or protective antibody response is critical for development of
      novel therapeutic strategies. Here, we show that paradoxically, a lower affinity
      antibody with restricted access to its epitope confers better neutralization than
      a higher affinity antibody against a similar epitope, suggesting that either
      subtle differences in epitope, or different characteristics of the GP1,2
      molecules themselves, confer differential neutralization susceptibility. Here, we
      also report the crystal structure of trimeric, prefusion GP1,2 from the original
      1976 Boniface variant of Sudan virus complexed with 16F6, the first antibody
      known to neutralize Sudan virus, and compare the structure to that of Sudan
      virus, variant Gulu. We discuss new structural details of the GP1-GP2 clamp,
      thermal motion of various regions in GP1,2 across the two viruses visualized,
      details of differential interaction of the crystallized neutralizing antibodies,
      and their relevance for virus neutralization.

PMID- 22590682
TI  - Bacteriophages with the ability to degrade uropathogenic Escherichia coli
      biofilms.
AB  - Escherichia coli-associated urinary tract infections (UTIs) are among the most
      common bacterial infections in humans. UTIs are usually managed with antibiotic
      therapy, but over the years, antibiotic-resistant strains of uropathogenic E.
      coli (UPEC) have emerged. The formation of biofilms further complicates the
      treatment of these infections by making them resistant to killing by the host
      immune system as well as by antibiotics. This has encouraged research into
      therapy using bacteriophages (phages) as a supplement or substitute for
      antibiotics. In this study we characterized 253 UPEC in terms of their biofilm
      forming capabilities, serotype, and antimicrobial resistance. Three phages were
      then isolated (vB_EcoP_ACG-C91, vB_EcoM_ACG-C40 and vB_EcoS_ACG-M12) which were
      able to lyse 80.5% of a subset (42) of the UPEC strains able to form biofilms.
      Correlation was established between phage sensitivity and specific serotypes of
      the UPEC strains. The phages' genome sequences were determined and resulted in
      classification of vB_EcoP_ACG-C91 as a SP6likevirus, vB_EcoM_ACG-C40 as a
      T4likevirus and vB_EcoS_ACG-M12 as T1likevirus. We assessed the ability of the
      three phages to eradicate the established biofilm of one of the UPEC strains used
      in the study. All phages significantly reduced the biofilm within 2-12 h of
      incubation.

PMID- 22590684
TI  - Megalocytiviruses.
AB  - The genus Megalocytivirus, represented by red sea bream iridovirus (RSIV), the
      first identified and one of the best characterized megalocytiviruses, Infectious
      spleen and kidney necrosis virus (ISKNV), the type species of the genus, and
      numerous other isolates, is the newest genus within the family Iridoviridae.
      Viruses within this genus are causative agents of severe disease accompanied by
      high mortality in multiple species of marine and freshwater fish. To date
      outbreaks of megalocytivirus-induced disease have occurred primarily in south
      east Asia and Japan, but infections have been detected in Australia and North
      America following the importation of infected ornamental fish. The first outbreak
      of megalocytiviral disease was recorded in cultured red sea bream (Pagrus major)
      in Japan in 1990 and was designated red sea bream iridovirus disease (RSIVD).
      Following infection fish became lethargic and exhibited severe anemia, petechiae
      of the gills, and enlargement of the spleen. Although RSIV was identified as an
      iridovirus, sequence analyses of RSIV genes revealed that the virus did not
      belong to any of the four known genera within the family Iridoviridae. Thus a
      new, fifth genus was established and designated Megalocytivirus to reflect the
      characteristic presence of enlarged basophilic cells within infected organs.
      Indirect immunofluorescence tests employing recently generated monoclonal
      antibodies and PCR assays are currently used in the rapid diagnosis of RSIVD. For
      disease control, a formalin-killed vaccine was developed and is now commercially
      available in Japan for several fish species. Following the identification of
      RSIV, markedly similar viruses such as infectious spleen and kidney necrosis
      virus (ISKNV), dwarf gourami iridovirus (DGIV), turbot reddish body iridovirus
      (TRBIV), Taiwan grouper iridovirus (TGIV), and rock bream iridovirus (RBIV) were
      isolated in East and Southeast Asia. Phylogenetic analyses of the major capsid
      protein (MCP) and ATPase genes indicated that although these viruses shared
      considerable sequence identity, they could be divided into three tentative
      species, represented by RSIV, ISKNV and TRBIV, respectively. Whole genome
      analyses have been reported for several of these viruses. Sequence analysis
      detected a characteristic difference in the genetic composition of
      megalocytiviruses and other members of the family in reference to the large and
      small subunits of ribonucleotide reductase (RR-1, RR-2). Megalocytiviruses
      contain only the RR-2 gene, which is of eukaryotic origin; whereas the other
      genera encode both the RR-1 and RR-2 genes which are thought to originate from
      Rickettsia-like alpha-proteobacteria.

PMID- 22590683
TI  - Nanotechnology and the treatment of HIV infection.
AB  - Suboptimal adherence, toxicity, drug resistance and viral reservoirs make the
      lifelong treatment of HIV infection challenging. The emerging field of
      nanotechnology may play an important role in addressing these challenges by
      creating drugs that possess pharmacological advantages arising out of unique
      phenomena that occur at the "nano" scale. At these dimensions, particles have
      physicochemical properties that are distinct from those of bulk materials or
      single molecules or atoms. In this review, basic concepts and terms in
      nanotechnology are defined, and examples are provided of how nanopharmaceuticals
      such as nanocrystals, nanocapsules, nanoparticles, solid lipid nanoparticles,
      nanocarriers, micelles, liposomes and dendrimers have been investigated as
      potential anti-HIV therapies. Such drugs may, for example, be used to optimize
      the pharmacological characteristics of known antiretrovirals, deliver anti-HIV
      nucleic acids into infected cells or achieve targeted delivery of antivirals to
      the immune system, brain or latent reservoirs. Also, nanopharmaceuticals
      themselves may possess anti-HIV activity. However several hurdles remain,
      including toxicity, unwanted biological interactions and the difficulty and cost
      of large-scale synthesis of nanopharmaceuticals.

PMID- 22590685
TI  - Daphne Genkwa sieb. Et zucc. Water-soluble extracts act on enterovirus 71 by
      inhibiting viral entry.
AB  - Dried flowers of Daphne genkwa Sieb. et Zucc. (Thymelaeaceae) are a Chinese
      herbal medicine used as an abortifacient with purgative, diuretic and anti
      inflammatory activities. However, the activity of this medicine against
      enteroviral infections has not been investigated. The water-extract of dried buds
      of D. genkwa Sieb. et Zucc. (DGFW) was examined against various strains of
      enterovirus 71 (EV71) by neutralization assay, and its initial mode of action was
      characterized by time-of-addition assay followed by attachment and penetration
      assays. Pretreatment of DGFW with virus abolished viral replication, indicating
      that DGFW inhibits EV71 by targeting the virus. GFW exerts its anti-EV71 effects
      by inhibiting viral entry without producing cytotoxic side effects and thus
      provides a potential agent for antiviral chemotherapeutics.

PMID- 22590686
TI  - Ready, set, fuse! The coronavirus spike protein and acquisition of fusion
      competence.
AB  - Coronavirus-cell entry programs involve virus-cell membrane fusions mediated by
      viral spike (S) proteins. Coronavirus S proteins acquire membrane fusion
      competence by receptor interactions, proteolysis, and acidification in endosomes.
      This review describes our current understanding of the S proteins, their
      interactions with and their responses to these entry triggers. We focus on
      receptors and proteases in prompting entry and highlight the type II
      transmembrane serine proteases (TTSPs) known to activate several virus fusion
      proteins. These and other proteases are essential cofactors permitting
      coronavirus infection, conceivably being in proximity to cell-surface receptors
      and thus poised to split entering spike proteins into the fragments that refold
      to mediate membrane fusion. The review concludes by noting how understanding of
      coronavirus entry informs antiviral therapies.

PMID- 22590687
TI  - RNA-sequencing analysis of 5' capped RNAs identifies many new differentially
      expressed genes in acute hepatitis C virus infection.
AB  - We describe the first report of RNA sequencing of 5' capped (Pol II) RNAs
      isolated from acutely hepatitis C virus (HCV) infected Huh 7.5 cells that
      provides a general approach to identifying differentially expressed annotated and
      unannotated genes that participate in viral-host interactions. We identified 100,
      684, and 1,844 significantly differentially expressed annotated genes in acutely
      infected proliferative Huh 7.5 cells at 6, 48, and 72 hours, respectively (fold
      change >= 1.5 and Bonferroni adjusted p-values < 0.05). Most of the
      differentially expressed genes (>80%) and biological pathways (such as
      adipocytokine, Notch, Hedgehog and NOD-like receptor signaling) were not
      identified by previous gene array studies. These genes are critical components of
      host immune, inflammatory and oncogenic pathways and provide new information
      regarding changes that may benefit the virus or mediate HCV induced pathology.
      RNAi knockdown studies of newly identified highly upregulated FUT1 and KLHDC7B
      genes provide evidence that their gene products regulate and facilitate HCV
      replication in hepatocytes. Our approach also identified novel Pol II unannotated
      transcripts that were upregulated. Results further identify new pathways that
      regulate HCV replication in hepatocytes and suggest that our approach will have
      general applications in studying viral-host interactions in model systems and
      clinical biospecimens.

PMID- 22590688
TI  - Paramyxovirus fusion and entry: multiple paths to a common end.
AB  - The paramyxovirus family contains many common human pathogenic viruses, including
      measles, mumps, the parainfluenza viruses, respiratory syncytial virus, human
      metapneumovirus, and the zoonotic henipaviruses, Hendra and Nipah. While the
      expression of a type 1 fusion protein and a type 2 attachment protein is common
      to all paramyxoviruses, there is considerable variation in viral attachment, the
      activation and triggering of the fusion protein, and the process of viral entry.
      In this review, we discuss recent advances in the understanding of paramyxovirus
      F protein-mediated membrane fusion, an essential process in viral infectivity. We
      also review the role of the other surface glycoproteins in receptor binding and
      viral entry, and the implications for viral infection. Throughout, we concentrate
      on the commonalities and differences in fusion triggering and viral entry among
      the members of the family. Finally, we highlight key unanswered questions and how
      further studies can identify novel targets for the development of therapeutic
      treatments against these human pathogens.

PMID- 22590690
TI  - Projective simulation for artificial intelligence.
AB  - We propose a model of a learning agent whose interaction with the environment is
      governed by a simulation-based projection, which allows the agent to project
      itself into future situations before it takes real action. Projective simulation
      is based on a random walk through a network of clips, which are elementary
      patches of episodic memory. The network of clips changes dynamically, both due to
      new perceptual input and due to certain compositional principles of the
      simulation process. During simulation, the clips are screened for specific
      features which trigger factual action of the agent. The scheme is different from
      other, computational, notions of simulation, and it provides a new element in an
      embodied cognitive science approach to intelligent action and learning. Our model
      provides a natural route for generalization to quantum-mechanical operation and
      connects the fields of reinforcement learning and quantum computation.

PMID- 22590691
TI  - Microcrystals coating the wing membranes of a living insect (Psocoptera:
      Psyllipsocidae) from a Brazilian cave.
AB  - Two specimens of Psyllipsocus yucatan with black wings were found with normal
      individuals of this species on guano piles produced by the common vampire bat
      Desmodus rotundus. These specimens have both pairs of wings dorsally and
      ventrally covered by a black crystalline layer. They did not exhibit any signs of
      reduced vitality in the field and their morphology is completely normal. This
      ultrathin (1.5 um) crystalline layer, naturally deposited on a biological
      membrane, is documented by photographs, SEM micrographs, energy dispersive
      spectroscopy (EDS) and X-ray diffractometry (XRD). The crystalline deposit
      contains iron, carbon and oxygen, but the mineral species could not be
      identified. Guano probably played a role in its formation; the presence of iron
      may be a consequence of the excretion of iron by the common vampire bat. This
      enigmatic phenomenon lacks obvious biological significance but may inspire bionic
      applications. Nothing similar has ever been observed in terrestrial arthropods.

PMID- 22590689
TI  - Co-circulation of four human coronaviruses (HCoVs) in Queensland children with
      acute respiratory tract illnesses in 2004.
AB  - Acute respiratory illnesses (ARIs) with unconfirmed infectious aetiologies peak
      at different times of the year. Molecular diagnostic assays reduce the number of
      unconfirmed ARIs compared to serology- or culture-based techniques. Screening of
      888 inpatient and outpatient respiratory specimens spanning late autumn through
      to early spring, 2004, identified the presence of a human coronavirus (HCoV) on
      74 occasions (8.3% of all specimens and 26.3% of all respiratory virus
      detections). Prevalence peaked in August (late winter in the southern hemisphere)
      when they were detected in 21.9% of specimens tested. HCoV-HKU1 and HCoV-OC43
      comprised 82.4% of all HCoVs detected. Positive specimens were used to develop
      novel reverse transcriptase real-time PCRs (RT-rtPCRs) for HCoV detection. An
      objective clinical severity score was assigned to each positive HCoV patient.
      Severity scores were similar to those from a random selection of young children
      who were positive for respiratory syncytial virus at a different time but from
      the same specimen population. During the cooler months of 2004, sensitive and
      specific RT-rtPCRs identified the concurrent circulation of all four HCoVs, a
      quarter of which co-occurred with another virus and most of which were from
      children under the age of two years.

PMID- 22590692
TI  - Application of (1)H and (31)P NMR to topological description of a model of
      biological membrane fusion: topological description of a model of biological
      membrane fusion.
AB  - The process of biological membrane fusion can be analysed by topological methods.
      Mathematical analysis of the fusion process of vesicles indicated two significant
      facts: the formation of an inner, transient structure (hexagonal phase - H(II))
      and a translocation of some lipids within the membrane. This shift had a vector
      character and only occurred from the outer to the inner layer. Model membrane
      composed of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and
      phosphatidylserine (PS) was studied. (31)P- and (1)H-NMR methods were used to
      describe the process of fusion. (31)P-NMR spectra of multilamellar vesicles (MLV)
      were taken at various temperatures and concentrations of Ca(2+) ions (natural
      fusiogenic agent). A (31)P-NMR spectrum with the characteristic shape of the
      H(II) phase was obtained for the molar Ca(2+)/PS ratio of 2.0. During the study,
      (1)H-NMR and (31)P-NMR spectra for small unilamellar vesicle (SUV), which were
      dependent on time (concentration of Pr(3+) ions was constant), were also
      recorded. The presence of the paramagnetic Pr(3+) ions permits observation of
      separate signals from the hydrophilic part of the inner and outer lipid bilayers.
      The obtained results suggest that in the process of fusion translocation of
      phospholipid molecules takes place from the outer to the inner layer of the
      vesicle and size of the vesicles increase. The NMR study has showed that the
      intermediate state of the fusion process caused by Ca(2+) ions is the H(II)
      phase. The experimental results obtained are in agreement with the topological
      model as well.

PMID- 22590693
TI  - Simultaneous siRNA-mediated silencing of pairs of genes coding for enzymes
      involved in glycosaminoglycan synthesis.
AB  - It has been demonstrated recently that it is possible to decrease expression of
      genes coding for enzymes involved in synthesis of glycosaminoglycans (GAGs) by
      using specific siRNAs which interfere with stability of particular mRNAs. This
      procedure has been proposed as a potential treatment for patients suffering from
      mucopolysaccharidoses, a group of inherited metabolic diseases caused by
      dysfunction of enzymes required for GAG degradation, and resultant storage of
      these compounds in cells of affected persons. Here, we asked if the simultaneous
      use two species of specific siRNAs aimed at silencing two genes involved in
      particular steps of GAG synthesis may be more effective than the use of single
      siRNA. We found that inhibition of GAG synthesis in cells treated with two siRNAs
      is generally more effective than using single siRNAs. However, the differences
      were not statistically significant, therefore the potential benefit from the use
      of two siRNAs over the use of a single siRNA is doubtful in the light of the cost
      benefit ratio and possibly stronger side-effects of the putative therapy.

PMID- 22590694
TI  - Curcumin and curcuminoids in quest for medicinal status.
AB  - Curcumin, known for thousands of years as an Ayurvedic medicine, and popular as a
      spice in Asian cuisine, has undergone in recent times remarkable transformation
      into a drug candidate with prospective multipotent therapeutic applications.
      Characterized by high chemical reactivity, resulting from an extended conjugated
      double bond system prone to nucleophilic attack, curcumin has been shown to
      interact with a plethora of molecular targets, in numerous experimental
      observations based on spectral, physicochemical or biological principles. The
      collected preclinical pharmacological data support traditional claims concerning
      the medicinal potential of curcumin and its congeners but at the same time point
      to their suboptimal properties in the ADME (absorption, distribution, metabolism
      and excretion) area.

PMID- 22590695
TI  - Endoscopic treatment of congenital tracheoesophageal fistula with submucosal
      resection and closure by clip.

PMID- 22590696
TI  - Time to think about physician wellness in gastroenterology.

PMID- 22590697
TI  - Canadian Digestive Health Foundation Public Impact Series 3: irritable bowel
      syndrome in Canada. Incidence, prevalence, and direct and indirect economic
      impact.
AB  - The Canadian Digestive Health Foundation initiated a scientific program to assess
      the incidence, prevalence, mortality and economic impact of digestive disorders
      across Canada in 2009. The current article presents the updated findings from the
      study concerning irritable bowel syndrome.

PMID- 22590698
TI  - Hepatitis B and the infected health care worker: public safety at what cost?
AB  - Public safety and the right of the health care worker to practise without
      prejudice based on underlying illness may be at odds for those affected by the
      hepatitis B virus (HBV). Nevertheless, HBV does not preclude entry into a health
      care profession, and the risk of transmission from health care worker to patient
      is not uniform across the spectrum of health care fields. In the present article,
      the authors present an overview of the literature regarding transmission of HBV
      from the health care worker to the patient, and the current recommendations that
      vary from province to province within Canada. The establishment of national
      guidelines to standardize monitoring of HBV infection among health care workers
      would improve health care workplace safety and patient care.

PMID- 22590699
TI  - Management of primary sclerosing cholangitis: conventions and controversies.
AB  - Primary sclerosing cholangitis (PSC) is a chronic inflammatory cholangiopathy
      that results in fibrotic strictures and dilations of the intra- and extrahepatic
      bile ducts. PSC is uncommon, occurs predominantly in males and has a strong
      association with inflammatory bowel disease. While the pathogenesis of PSC has
      not been fully elucidated, emerging evidence supports roles for the innate and
      adaptive immune systems, and genome-wide analyses have identified several genetic
      associations. Using the best available evidence, the present review summarizes
      the current understanding of the diagnosis, pathogenesis and management of PSC.
      Despite its rarity, there is an urgent need for collaborative research efforts to
      advance therapeutic options for PSC beyond liver transplantation.

PMID- 22590700
TI  - Small bowel enteroscopy.
AB  - Over the past decade, the advent of capsule endoscopy and balloon-assisted
      enteroscopy has revolutionized the approach to small intestinal diseases. The
      small bowel is no longer out of reach, and has fallen within the diagnostic and
      therapeutic realm of the gastrointestinal endoscopist. Double-balloon enteroscopy
      was the first type of balloon-assisted endoscopy and is the method for which
      there are the most data. Single-balloon enteroscopy has since been introduced as
      an alternative balloon-assisted method, followed more recently by the development
      of spiral overtube-assisted enteroscopy. The purpose of the present article is to
      review these methods of small bowel enteroscopy and to discuss the latest
      developments. While the investigation of small bowel diseases cannot be addressed
      without considering the central role of capsule endoscopy, a detailed assessment
      is beyond the scope of the present article, and capsule endoscopy will only be
      discussed as it pertains to enteroscopy.

PMID- 22590701
TI  - Implementation of a multidisciplinary team approach and fish oil emulsion
      administration in the management of infants with short bowel syndrome and
      parenteral nutrition-associated liver disease.
AB  - OBJECTIVE: To describe the authors' experience with the implementation of a
      multidisciplinary approach and use of fish oil emulsion (FOE) in the management
      of infants with short bowel syndrome (SBS) and parenteral nutrition-associated
      liver disease (PNALD). METHODS: Between August 2006 and June 2009, four cases of
      SBS and severe PNALD were managed by the team using specifically developed
      protocols. The FOE was initiated if serum direct bilirubin levels were >=100
      umol/L. To quantify the degree of exposure to high serum direct bilirubin levels
      over time, the area under the curve (AUC) for each patient was calculated before
      and after initiation of FOE. Linear regression analyses were performed to
      evaluate correlations between the AUC, duration of cholestasis and initiation of
      FOE. RESULTS: All patients survived and no complications were observed during the
      study period. After the first patient, FOE was initiated progressively earlier,
      but poor correlation between the AUC before and after its introduction was
      observed (r(2)=0.41924). However, there was strong correlation between the
      duration of PNALD before FOE initiation and time to resolution (r(2)=0.72133):
      the earlier the FOE was initiated, the shorter the time to resolution.
      CONCLUSION: The authors report a positive experience with the implementation of a
      multidisciplinary approach and the use of FOE in infants with SBS and severe
      PNALD. The earlier the FOE was initiated during the cholestatic process, the
      shorter the time to resolution. The present study is a hypothesis generator,
      raising the question of whether an earlier introduction of this particular
      therapy can effectively shorten the cholestasis process in these patients.

PMID- 22590702
TI  - A cross-sectional study of the association between overnight call and irritable
      bowel syndrome in medical students.
AB  - BACKGROUND: Shift work has been associated with irritable bowel syndrome (IBS),
      which includes gastrointestinal symptoms such as abdominal pain, constipation and
      diarrhea. Overnight call shifts also lead to a disruption of the endogenous
      circadian rhythm. HYPOTHESIS: Medical students who perform intermittent overnight
      call shifts will demonstrate a higher prevalence of IBS symptoms when compared
      with medical students who perform no overnight call shifts. METHODS: First- and
      second-year (preclinical) medical students have no overnight call requirements,
      whereas third- and fourth-year medical (clerkship) students do have overnight
      call requirements. All medical students at the Schulich School of Medicine and
      Dentistry (London, Ontario) were invited to complete an anonymous, web-based
      survey or an identical paper copy that included demographic data, the Rome III
      questionnaire and the IBS-Quality of Life measure (IBS-QOL). The prevalence of
      IBS symptoms and quality of life secondary to those symptoms were determined.
      RESULTS: Data were available for 247 medical students (110 preclinical students,
      118 clerkship students and 19 excluded surveys). There was no significant
      difference in the presence of IBS between preclinical and clerkship students (21
      of 110 [19.1%] versus 26 of 118 [22.0%]; P=0.58). The were no significant
      differences in mean (+/- SD) IBS-QOL score of those with IBS between preclinical
      (43.5+/-8.3) and clerkship students (45.7+/-13.8) (P=0.53). CONCLUSIONS:
      Participation in overnight call was not associated with the development of IBS or
      a lower quality of life secondary to IBS in medical students.

PMID- 22590703
TI  - A novel screen-printed electrode array for rapid high-throughput detection.
AB  - A novel multi-channel electrode array sensing device was fabricated by screen
      printing techniques using 96-well plate as the template. To confirm its practical
      value, we developed a one-step preparation of multi-walled carbon nanotubes
      (MWCNTs) doped electrode array by an ink containing MWCNTs, which was applied to
      the simultaneous detection of a variety of biological samples and environmental
      pollutants. Results demonstrated that the designed sensing device could carry out
      the multiple measurements of different analytes at the same time, while MWCNTs
      enhanced the electrocatalytic activity of electrodes toward electroactive
      molecules. The required amount of each sample was only ~200 MUL. Moreover, the
      excellent differential pulse voltammetric (DPV) response toward dopamine,
      hydroquinone and catechol was obtained and the detection limits was determined to
      be 0.337, 0.289 and 0.369 MUM, respectively. Comparing it with the traditional
      screen-printed electrode (SPE), this sensing device possesses the advantages of
      high-throughput, fast electron transfer rate for electrodes, short-time analysis
      and low sample consumption.

PMID- 22590704
TI  - Molecular assembly composed of a dendrimer template and block polypeptides
      through stereocomplex formation.
AB  - A 2nd generation polyamideamine (PAMAM) dendrimer bearing right-handed helices to
      its eight terminals was shown to accommodate eight left-handed helices via
      stereocomplex formation to generate molecular assemblies of disk structure with
      13-14 nm diameter and 6 nm thickness.

PMID- 22590705
TI  - Phthalocyanines: a new class of G-quadruplex-ligands with many potential
      applications.
AB  - A G-quadruplex is a four-stranded DNA structure featuring stacked guanine
      tetrads, G-quartets. Formation of a G-quadruplex in telomere DNA can inhibit
      telomerase activity; therefore, development of G-quadruplex-ligands, which induce
      and/or stabilize G-quadruplexes, has become an area of great interest.
      Phthalocyanine derivatives have substantial potential as high-affinity G
      quadruplex-ligands because these planar chromophores are similar in size and
      shape to the G-quartets. Here, we focus on the latest findings on phthalocyanine
      derivatives as G-quadruplex-ligands, and discuss the mechanisms by which
      phthalocyanines bind to G-quadruplexes with high affinity and selectivity. We
      also discuss potential biomedical and organic electronic applications of
      phthalocyanines that are dependent on their photophysical properties.

PMID- 22590706
TI  - Insulated donor-pi-acceptor systems based on fluorene-phosphine oxide hybrids for
      non-doped deep-blue electroluminescent devices.
AB  - An ambipolar ternary deep-blue emitter with CIE coordinates of (0.15, 0.07) and
      high electroluminescent performance was constructed on the basis of an insulated
      donor-pi-acceptor system through an indirect linkage.

PMID- 22590707
TI  - Toward biodegradable nanogel star polymers via organocatalytic ROP.
AB  - Organocatalytic ring opening polymerization (OROP) is used to effect the rapid,
      scalable, room temperature formation of size-controlled, highly uniform,
      polyvalent, nanogel star polymer nanoparticles of biodegradable composition.

PMID- 22590708
TI  - Phosphine oxide functionalised imidazolium ionic liquids as tuneable ligands for
      lanthanide complexation.
AB  - A series of novel, phosphine oxide functionalised ionic liquids have been
      synthesised and their application as tuneable lanthanide complexing agents is
      demonstrated.

PMID- 22590709
TI  - Solution processed high performance pentacene thin-film transistors.
AB  - High performance thin-film transistors were fabricated using a new precursor of
      pentacene through a multiple spin-heat procedure. High quality pentacene thin
      films can be prepared by this method and hence a FET device can be made in a top
      contact configuration. The device exhibited a remarkable field-effect mobility of
      0.38 cm(2) V(-1) s(-1) with an on/off ratio of 10(6).

PMID- 22590710
TI  - Stimuli-responsive 2D polyelectrolyte photonic crystals for optically encoded pH
      sensing.
AB  - A versatile photonic crystal sensing motif based on a two-dimensional (2D)
      inverse opal monolayer of stimuli-responsive polyelectrolyte gel with tunable
      optical properties is reported. The photonic membrane shows prompt response to pH
      and can be readily read out from either its optical spectra or interference
      colours.

PMID- 22590711
TI  - Recoverable organorhodium-functionalized polyhedral oligomeric silsesquioxane: a
      bifunctional heterogeneous catalyst for asymmetric transfer hydrogenation of
      aromatic ketones in aqueous medium.
AB  - A bifuctional heterogeneous chiral rhodium catalyst exhibited excellent catalytic
      activity and enantioselectivity in asymmetric transfer hydrogenation of aromatic
      ketones and their analogues in aqueous medium, which could be recovered easily
      and used repetitively without affecting obviously its enantioselectivity.

PMID- 22590712
TI  - Sensitive fluorescence biosensor for folate receptor based on terminal protection
      of small-molecule-linked DNA.
AB  - Based on the specific folic acid-folate receptor (FA-FR) interaction,
      macromolecular FR can bind with FA-linked DNA-small molecule chimeras, which can
      prevent enzymolysis by exonuclease III (Exo III), enabling a novel fluorescence
      biosensor for FR to be developed using quinaldine red as a G-quadruplex-binding
      probe.

PMID- 22590714
TI  - Retraction: Vascular endothelial growth factor in cerebral ischemia.

PMID- 22590713
TI  - The prevalence and burden of primary headaches in China: a population-based door
      to-door survey.
AB  - OBJECTIVES: In the absence of reliable data on the prevalence and burden of
      primary headache disorders in the mainland of China, a population-based survey
      was initiated by Lifting The Burden: the Global Campaign against Headache.
      METHODS: Throughout all regions of China, 5041 non-related adult respondents aged
      18-65 years were randomly sampled from the general population according to the
      expanded programme on immunization method established by World Health
      Organization. They were visited by door-to-door calling and surveyed using the
      structured questionnaire developed by Lifting The Burden, translated into Chinese
      and adapted to Chinese culture after a pilot study. RESULTS: The responder rate
      was 94.1%.The estimated 1-year prevalence of primary headache disorders was 23.8%
      (95%confidence interval 22.6-25.0%), of migraine 9.3% (95% confidence interval
      8.5-10.1%), of tension-type headache (TTH) 10.8%(9.9-11.6%), and of chronic daily
      headache (CDH) 1.0% (0.7-1.2%). Of respondents with migraine, TTH, and CDH,
      moderate or severe impact and therefore high need for effective medical care were
      reported by 38.0%, 23.1%, and 47.9%, respectively.The World Health Organization
      quality of life-8 questionnaire showed that all 3 types of headache reduced life
      quality. The total estimated annual cost of primary headache disorders, including
      migraine,TTH, and CDH was CNY 672.7 billion, accounting for 2.24% of gross
      domestic product (GDP) (direct cost: CNY 108.8 billion, 0.36% of GDP; indirect
      cost: CNY 563.9 billion, 1.88%of GDP). CONCLUSION: The prevalence of primary
      headaches is high in China and not dissimilar from the world average. These
      headaches cause disability, impair work, study and daily activities, decrease
      life quality, and bring about a heavy and hitherto unrecognized socioeconomic
      burden.

PMID- 22590715
TI  - Does chromatin modulation provide the first wet biomarker for Huntington's
      disease?

PMID- 22590716
TI  - Can long-term levodopa treatment induce neuropathy in PD?

PMID- 22590717
TI  - LRRK2: Understanding the role of common and rare variants in Parkinson's disease.

PMID- 22590718
TI  - Teaching case: new onset migraine with aura?

PMID- 22590719
TI  - Expert commentary. Teaching case: New onset migraine with aura?

PMID- 22590720
TI  - Comprehensive investigation of genetic variation in the 8q24  region and multiple
      myeloma risk in the IMMEnSE consortium.
AB  - Genome-wide association studies (GWAS) have shown that the 8q24 region harbours
      multiple independent cancer susceptibility loci, even though it is devoid of
      genes. Given that no GWAS data are currently available for multiple myeloma (MM),
      we tested the hypothesis that genetic variants in this region could play a role
      in MM risk. We genotyped 20 single nucleotide polymorphisms of 8q24 in 1188 MM
      cases and 2465 controls and found a statistically significant (P = 0.0022)
      association between rs2456449 and MM risk. These data provide further evidence
      that the genetic variability in the 8q24 region is associated with cancer risk,
      particularly haematological malignancies.

PMID- 22590721
TI  - Clinical variability in early speech-language development in females with Rett
      syndrome.

PMID- 22590722
TI  - Does severe hypoglycaemia disrupt academic achievement in children with early
      onset diabetes?

PMID- 22590723
TI  - Academic skills in children with early-onset type 1 diabetes: the effects of
      diabetes-related risk factors.
AB  - AIM: The study aimed to assess the effects of diabetes-related risk factors,
      especially severe hypoglycaemia,on the academic skills of children with early
      onset type 1 diabetes mellitus (T1DM). METHOD: The study comprised 63 children
      with T1DM (31 females, 32 males; mean age 9 y 11 mo,SD 4 mo) and 92 comparison
      children without diabetes (40 females, 52 males;mean age 9 y 9 mo,SD 3 mo).
      Children were included if T1DM had been diagnosed before the age of 5 years and
      if they were aged between 9 and 10 years at the time of study. Children were not
      included if their native language was not Finnish and if they had a diagnosed
      neurological disorder that affected their cognitive development. Among the T1DM
      group, 37 had and 26 had not experienced severe hypoglycaemia and 26 had avoided
      severe hypoglycaemia. Severe hypoglycaemia, diabetic ketoacidosis(DKA), and
      glycaemic control were used as T1DM-related factors. Task performance in reading,
      spelling, and mathematics was compared among the three groups, and the effects of
      the T1DM-related factors were analysed with general linear models. RESULTS: The
      groups with (p<0.001) and without (p=0.001) severe hypoglycaemia demonstrated a
      poorer performance than the comparison group in spelling, and the group without
      severe hypoglycaemia showed a poorer performance than the comparison group in
      mathematics (p=0.003).Severe hypoglycaemia, DKA, and recent glycaemic control
      were not associated with poorer skills,but poorer first-year glycaemic control
      was associated with poorer spelling (p=0.013). INTERPRETATION: An early onset of
      T1DM can increase the risk of learning problems, independently of the history of
      severe hypoglycaemia or DKA. Poorer glycaemic control after the first year of
      T1DM is associated with a poorer acquisition of academic skills indicating the
      effect of the timing of metabolic aberrations on cognitive development.

PMID- 22590724
TI  - Histone deacetylase (HDAC) inhibitors targeting HDAC3 and HDAC1 ameliorate
      polyglutamine-elicited phenotypes in model systems of Huntington's disease.
AB  - We have previously demonstrated amelioration of Huntington's disease (HD)-related
      phenotypes in R6/2 transgenic mice in response to treatment with the novel
      histone deacetylase (HDAC) inhibitor 4b. Here we have measured the selectivity
      profiles of 4b and related compounds against class I and class II HDACs and have
      tested their ability to restore altered expression of genes related to HD
      pathology in mice and to rescue disease effects in cell culture and Drosophila
      models of HD. R6/2 transgenic and wild-type (wt) mice received daily injections
      of HDAC inhibitors for 3 days followed by real-time PCR analysis to detect
      expression differences for 13 HD-related genes. We find that HDACi 4b and 136,
      two compounds showing high potency for inhibiting HDAC3 were most effective in
      reversing the expression of genes relevant to HD, including Ppp1r1b, which
      encodes DARPP-32, a marker for medium spiny striatal neurons. In contrast,
      compounds targeting HDAC1 were less effective at correcting gene expression
      abnormalities in R6/2 transgenic mice, but did cause significant increases in the
      expression of selected genes. An additional panel of 4b-related compounds was
      tested in a Drosophila model of HD and in STHdhQ111 striatal cells to further
      distinguish HDAC selectivity. Significant improvement in huntingtin-elicited
      Drosophila eye neurodegeneration in the fly was observed in response to treatment
      with compounds targeting human HDAC1 and/or HDAC3. In STHdhQ111 striatal cells,
      the ability of HDAC inhibitors to improve huntingtin-elicited metabolic deficits
      correlated with the potency at inhibiting HDAC1 and HDAC3, although the IC50
      values for HDAC1 inhibition were typically 10-fold higher than for inhibition of
      HDAC3. Assessment of HDAC protein localization in brain tissue by Western blot
      analysis revealed accumulation of HDAC1 and HDAC3 in the nucleus of HD transgenic
      mice compared to wt mice, with a concurrent decrease in cytoplasmic localization,
      suggesting that these HDACs contribute to a repressive chromatin environment in
      HD. No differences were detected in the localization of HDAC2, HDAC4 or HDAC7.
      These results suggest that inhibition of HDACs 1 and 3 can relieve HD-like
      phenotypes in model systems and that HDAC inhibitors targeting these isotypes
      might show therapeutic benefit in human HD.

PMID- 22590726
TI  - Changes in the root-associated fungal communities along a primary succession
      gradient analysed by 454 pyrosequencing.
AB  - We investigated changes in the root-associated fungal communities associated with
      the ectomycorrhizal herb Bistorta vivipara along a primary succession gradient
      using 454 amplicon sequencing. Our main objective was to assess the degree of
      variation in fungal richness and community composition as vegetation cover
      increases along the chronosequence. Sixty root systems of B. vivipara were
      sampled in vegetation zones delimited by dated moraines in front of a retreating
      glacier in Norway. We extracted DNA from rinsed root systems, amplified the ITS1
      region using fungal-specific primers and analysed the amplicons using 454
      sequencing. Between 437 and 5063 sequences were obtained from each root system.
      Clustering analyses using a 98.5% sequence similarity cut-off yielded a total of
      470 operational taxonomic units (OTUs), excluding singletons. Between eight and
      41 fungal OTUs were detected within each root system. Already in the first stage
      of succession, a high fungal diversity was present in the B. vivipara root
      systems. Total number of OTUs increased significantly along the gradient towards
      climax vegetation, but the average number of OTUs per root system stayed
      unchanged. There was a high patchiness in distribution of fungal OTUs across root
      systems, indicating that stochastic processes to a large extent structure the
      fungal communities. However, time since deglaciation had impact on the fungal
      community structure, as a systematic shift in the community composition was
      observed along the chronosequence. Ectomycorrhizal basidiomycetes were the
      dominant fungi in the roots of B. vivipara, when it comes to both number of OTUs
      and number of sequences.

PMID- 22590725
TI  - Foxo/atrogin induction in human and experimental myositis.
AB  - Skeletal muscle atrophy can occur rapidly in various fasting, cancerous, systemic
      inflammatory, deranged metabolic or neurogenic states. The ubiquitin ligase
      Atrogin-1 (MAFbx) is induced in animal models of these conditions, causing
      excessive myoprotein degradation. It is unknown if Atrogin upregulation also
      occurs in acquired human myositis. Intracellular beta-amyloid (Abetai),
      phosphorylated neurofilaments, scattered infiltrates and atrophy involving
      selective muscle groups characterize human sporadic Inclusion Body Myositis
      (sIBM). In Polymyositis (PM), inflammation is more pronounced and atrophy is
      symmetric and proximal. IBM and PM share various inflammatory markers. We found
      that forkhead family transcription factor Foxo3A is directed to the nucleus and
      Atrogin-1 transcript is increased in both conditions. Expression of Abeta in
      transgenic mice and differentiated C2C12 myotubes was sufficient to upregulate
      Atrogin-1 mRNA and cause atrophy. Abetai reduces levels of p-Akt and downstream p
      Foxo3A, resulting in Foxo3A translocation and Atrogin-1 induction. In a mouse
      model of autoimmune myositis, cellular inflammation alone was associated with
      similar Foxo3A and Atrogin changes. Thus, either Abetai accumulation or cellular
      immune stimulation may independently drive muscle atrophy in sIBM and PM,
      respectively, through pathways converging on Foxo and Atrogin-1. In sIBM it is
      additionally possible that both mechanisms synergize.

PMID- 22590727
TI  - A comparative study of ancient sedimentary DNA, pollen and macrofossils from
      permafrost sediments of northern Siberia reveals long-term vegetational
      stability.
AB  - Although ancient DNA from sediments (sedaDNA) has been used to investigate past
      ecosystems, the approach has never been directly compared with the traditional
      methods of pollen and macrofossil analysis. We conducted a comparative survey of
      18 ancient permafrost samples spanning the Late Pleistocene (46-12.5 thousand
      years ago), from the Taymyr Peninsula in northern Siberia. The results show that
      pollen, macrofossils and sedaDNA are complementary rather than overlapping and,
      in combination, reveal more detailed information on plant palaeocommunities than
      can be achieved by each individual approach. SedaDNA and macrofossils share
      greater overlap in plant identifications than with pollen, suggesting that
      sedaDNA is local in origin. These two proxies also permit identification to lower
      taxonomic levels than pollen, enabling investigation into temporal changes in
      species composition and the determination of indicator species to describe
      environmental changes. Combining data from all three proxies reveals an area
      continually dominated by a mosaic vegetation of tundra-steppe, pioneer and wet
      indicator plants. Such vegetational stability is unexpected, given the severe
      climate changes taking place in the Northern Hemisphere during this time, with
      changes in average annual temperatures of >22  degrees C. This may explain the
      abundance of ice-age mammals such as horse and bison in Taymyr Peninsula during
      the Pleistocene and why it acted as a refugium for the last mainland woolly
      mammoth. Our finding reveals the benefits of combining sedaDNA, pollen and
      macrofossil for palaeovegetational reconstruction and adds to the increasing
      evidence suggesting large areas of the Northern Hemisphere remained ecologically
      stable during the Late Pleistocene.

PMID- 22590728
TI  - Biomonitoring 2.0: a new paradigm in ecosystem assessment made possible by next
      generation DNA sequencing.
AB  - Biological monitoring has failed to develop from simple binary assessment
      outcomes of the impacted/unimpacted type, towards more diagnostic frameworks,
      despite significant scientific effort over the past fifty years. It is our
      assertion that this is largely because of the limited information content of
      biological samples processed by traditional morphology-based taxonomy, which is a
      slow, imprecise process, focused on restricted groups of organisms. We envision a
      new paradigm in ecosystem assessment, which we refer to as 'Biomonitoring 2.0'.
      This new schema employs DNA-based identification of taxa, coupled with high
      throughput DNA sequencing on next-generation sequencing platforms. We discuss the
      transformational nature of DNA-based approaches in biodiversity discovery and
      ecosystem assessment and outline a path forward for their future widespread
      application.

PMID- 22590729
TI  - The placement of an intravenous cannula is always necessary during general
      anesthesia in children: a pro-con debate. The case for intravenous access.

PMID- 22590730
TI  - [SIADH - a "shambles"].

PMID- 22590731
TI  - What is an editorial registrar?

PMID- 22590732
TI  - Meeting the challenges, serving the public: labs of the year 2012.

PMID- 22590733
TI  - John Ledek guides BD's efforts to offer labs innovative solutions for
      preanalytical systems.

PMID- 22590734
TI  - [The changes of metabolism in myocardium at ischemia-reperfusion and activating
      of the ATP-sensitive potassium channels].
AB  - In experiments on the anaesthetized dogs with modeling of experimental ischemia
      (90 min) and reperfusion (180 min) it was investigated the changes of biochemical
      processes in the different areas of heart (intact, risk and necrotic zone) during
      intragastric introduction of medicinal form (tablets) of flocalin (the fluorine
      containing opener of ATP-sensitive potassium channels) in a dose 2,2 mg/kg. The
      data analysis allowed to define a few possible cardioprotective mechanisms of
      flocalin action at ischemia-reperfusion conditions: the preservation of
      sufficient levels of de novo (by cNOS) NO synthesis, an inhibition of de novo (by
      iNOS) and salvage (by NADH-dependent nitratreductase) NO synthesis, an inhibition
      of L-arginine degradation by arginase, an inhibition of oxidizing metabolism due
      to limitation of ROS and RNS generation, inhibition of free arachidonic acid and
      eicosanoids synthesis, inhibition of ATP and GTP degradations and, possibly,
      stimulation of protective haem degradation. These changes may prevent formation
      of toxic peroxynitrite and suggest the possibility of participating in flocalin
      mediated cardioprotective effects of warning a mitochondrial permeability
      transition pore (MPTP) opening and inhibition of apoptosis and/or necrosis of
      cardiomyocytes induced by it.

PMID- 22590736
TI  - [The antiviral activity of diphenyl derivatives in different model systems].
AB  - In experiments on two model systems L929/VSV and RF/ HSV-1 in vitro we have
      studied the antiviral activity of new structural analogues of tilorone--4,4'
      bis[2-(diethyl-amino)ethoxy]diphenyl dihydrochloride and 2-methoxy-carbonyl-4-4'
      bis[2-(diethylamino)ethoxy]diphenyl dihydrochloride. In experiments the tested
      substances were administered in preventive and therapeutic schemes. The
      preventive scheme confirms the existence of a correlation between IFN production
      under the influence of tested substances and their antiviral activity. It is
      shown that diphenyls are able to inhibit the development of viral cytopathic
      effect induced by DNA- and RNA-containing viruses. Diphenyl derivatives are less
      toxic than tilorone and could be considered as promising substances for further
      research to develop new antiviral drugs.

PMID- 22590735
TI  - [Arginase-nitric oxide synthase system changes due to adaptation to swimming in
      adult and aged rat hearts].
AB  - We tested the physiological indices of adult rat heart beat for the adaptation to
      prolonged physical exercise (swimming). It was shown that the stimulation of NO
      production in the heart mitochondria of trained adult rats improves both systolic
      and diastolic heart function. In adult rats trained by swimming the activity of
      both de novo and salvage enzymes of nitric oxide synthesis studied (iNOS, cNOS,
      nitratreductase) were increased in heart mitochondria, whereas in the old rats
      only the activity of oxidative de novo enzymes. Training reduced the nitrate
      pools only in the mitochondria from adult rats and the urea pools in mitochondria
      from old rats. Intramitochondrial nitrite pools were unchanged. In adult rats,
      mitochondrial H2O2 pools increased after training, whereas in the old rats they
      were reduced, the level of uric acid (a marker ofxanthinoxydase activity) in
      ageing rats after training period was declined. Swimming training resulted in a
      significant increase in the value of "oxygenation index" in mitochondria of adult
      rats and decreased the activity of mitochondrial arginase II. The results suggest
      that swimming is one of the methods of physical load stimulates NO production in
      the mitochondria of adult and old rats and therefore could be considered as an
      effective non-pharmacological tool for correction of mitochondrial dysfunction in
      adults and aging heart.

PMID- 22590737
TI  - [Superposition of the motor commands during creation of static efforts by human
      hand muscles].
AB  - The features of superposition of central motor commands (CMCs) have been studied
      during generation of the "two-joint" isometric efforts by hand. The
      electromyogram (EMG) amplitudes which were recorded from the humeral belt and
      shoulder muscles have been used for estimation of the CMCs intensity. The forces
      were generated in the horizontal plane of the work space; the position of arm was
      fixed. Two vectors of equal amplitudes and close direction and their geometrical
      sum were compared. The hypothesis of the CMCs' superposition in the task of the
      force vector summation has been examined. The directions of the constituent and
      resulting forces with satisfactory superposition of the CMCs were defined.
      Differences in the co-activation patterns for flexor and extensor muscles of both
      joints were shown. The high level of the flexor muscles activity has been
      observed during extension efforts, while the flexion directions demonstrated much
      weaker activation of the extensor muscles.

PMID- 22590738
TI  - [Correction of age-related changes in sphingolipid content in rat tissues by acid
      sphingomyelinase inhibition].
AB  - Because reduction of sphingomyelin and ceramide accumulation in aging are
      associated with the development of a wide variety of pathologies, finding the
      ways of normalizing the sphingolipid exchange is becoming actual. As the ASM is a
      key enzyme of the sphingolipid exchange, in the present study we have
      investigated the effect of an ASM inhibitor imipramine on the ceramide and
      sphingomyelin content in the tissues of old rats. The introduction of imipramine
      elevates the sphingomyelin level and reduces the ceramide/sphingomyelin ratio in
      the liver, heart and brain of old rats. The hippocampus is most sensitive to the
      imipramine effects. These data suggest that imipramine is an effective modulator
      of sphingolipid content in the body of old rats. The age-related changes in the
      ceramide and sphingomyelin content in the tissues are higly determined by the
      activation of acid sphingomyelinase in the process of aging.

PMID- 22590739
TI  - [Effects of chronic caloric restriction on the age-associated peculiarities of
      explorative behaviour in rats].
AB  - Long-term caloric restriction (CR) has been reported to extend the life spans,
      delay the onset and decrease the incidence of a broad spectrum of age-associated
      diseases. However, its effect on rat explorative behaviour is still unclear. In
      the present study, a number of behavioural measures were continuously monitored
      in 3-, 12-, 24-25-, 28-29- and 35-44-month-old male Wistar rats that were fed
      either ad libitum or placed on a caloric restricted diet. A gradual decline in
      locomotor activity of the ad libitum fed rats has been determined during aging in
      the open field test. In the CR groups, 3-month-old rats exhibited lower levels of
      exploratory behavior, compared to rats on the control diet. 24-25-month-old CR
      rats exhibited higher levels of exploratory behaviour, compared to ad libitum fed
      animals of the same age. Chronic dietary restriction nullified the age-dependent
      decline in locomotor activity and explorative behaviour of rats.

PMID- 22590740
TI  - [Characterization of the latent periods of excitation and shortening of anterior
      tibial muscle of white rats depending on the blood level of triiodothyronine].
AB  - In experiments in situ it was shown an expressed negative correlation between the
      duration of latent periods of excitation and contraction of the anterior tibial
      muscle of white rats and the blood level of free triiodothyronine. The difference
      in mean values of latent periods at starting and final points of scale of
      physiological fluctuations of triiodothyronine level amounted 15.5% and 37.0%
      respectively. In parallel with lengthening of latent period of anterior tibial
      muscle excitation it was found an increase in latent period of this muscle
      contraction. Interestingly, at high values of the latent periods of excitation
      such dependence disappeared.

PMID- 22590741
TI  - [Psychophysiological analysis of efficiency of cerebral hemodynamics with
      dopplerographic and reoencephalographic imaging].
AB  - The authors designed the integrated diagnostic test as a model for
      psychophysiological assessment and prediction of the effectiveness of cerebral
      hemodynamics in subjects. The test includes the recording of blood flow velocity
      in the CCA and the level of psychopathisation.

PMID- 22590742
TI  - [Features of systemic microcirculation in patients with chronic dermatoses].
AB  - We investigated the parameters of microcirculation of eyes in women of 36-55
      years age with atopic dermatitis, microbic eczema and diffuse alopecia. In
      persons with atopic dermatitis the signs of non-uniformity of capillary caliber
      and their branching were observed. These abnormalities were accompanied by an
      increase in the quantities of functioning anastomoses, loops and corners of
      capillaries. Abnormalities of microcirculation which accompany microbic eczema
      included alterations in microvessel parallelism, microaneurysm, venous
      sacculation, pathological forms of branching, vascular new growth, an increased
      number of functioning anastomose and presence of avascular fields. Diffuse
      alopecia was characterized by the venous sacculation, branching microveins, non
      uniformity of their diameter and spasm of arteriols.

PMID- 22590743
TI  - [Effects of diazoxide on the mitochondrial membrane potential and ROS generation
      in rat uterus cells].
AB  - In the present study we demonstrate partial depolarization of the mitochondrial
      inner membrane from the rat uterus cells upon activation of mitochondrial ATP
      sensitive K(+)-channel (mitoK(ATP)) with diazoxide. The estimated affinity
      constant of diazoxide to mitoK(ATP) from rat uterus cells is (5.01 +/- 1.47) 10(
      6) M. We also observed an enhanced generation of reactive oxygen species after
      addition of diazoxide. Both effects were effectively eliminated by glybenclamide,
      blocker of the ATP-sensitive K+ channel. Our results indicate that activation of
      mitoK(ATP) in rat uterus cells leads to a partial depolarization of mitochondrial
      membrane and an increase in ROS concentration.

PMID- 22590744
TI  - [NF-kB activation as a molecular basis of pathological process by metabolic
      syndrome].
AB  - The paper examines the formation of evolutionary advanced causal factors set in
      modern conditions which may cause new pathological condition (state), being
      implemented through evolutionary fixed and standard pathological processes. The
      analysis of the notion of "metabolic syndrome" and its components has been
      performed. The correlation between insulin resistance, chronic inflammation,
      arterial hypertension, endothelial dysfunction and dyslipidemia has been
      indicated as the manifestations of one pathologic process, the central molecular
      basis of which is the activation of NF-kB. At the current stage it has been
      suggested to set up the conception of NF-kB permanent (long-lasting, low grade)
      activation as a possible model of pathological process.

PMID- 22590745
TI  - Special issue dedicated to Joska Hamori.

PMID- 22590746
TI  - Abstracts of the Annual Meeting of the Royal Belgian Society for Ear, Nose and
      Throat, Head and Neck Surgery, March 24, 2012, Brussels, Belgium.

PMID- 22590747
TI  - Abstracts of the 8th Congress of the Croatian Cardiac Society with international
      participation, October 21-24, 2010, Opatija, Croatia.

PMID- 22590748
TI  - Editorial critique.

PMID- 22590749
TI  - Editorial critique.

PMID- 22590750
TI  - Editorial critique.

PMID- 22590751
TI  - Editorial critique.

PMID- 22590752
TI  - Editorial critique.

PMID- 22590753
TI  - Editorial critique.

PMID- 22590754
TI  - [Peoples without history or writing in Athens on the Spree: anthropology as a
      criticism of history in Imperial Germany].

PMID- 22590755
TI  - [Force and violence in the early modern period:    forms and changes in forms of
      power].

PMID- 22590756
TI  - [Voices of silence: memories of rape in the capital cities of Hitler's "first
      victim" (Vienna) and "last ally" (Budapest) in 1945].

PMID- 22590757
TI  - [Executioner, medicine, and carrying out punishment in    the early modern era].

PMID- 22590758
TI  - The effect of health information technology on quality in U.S. hospitals.

PMID- 22590759
TI  - A federalist's dilemma: three cases before the U.S. Supreme Court pose a conflict
      for some who usually back states' rights.

PMID- 22590760
TI  - Chronic cost of diabetes: effectively treating the epidemic could mean big
      savings for states and healthier patients.

PMID- 22590761
TI  - [Social disciplining through punishment? Objectives of early modern    policing
      ordinances and state sanctions].

PMID- 22590762
TI  - [Labor market policy,    migration, and the legal stigmatization of foreigners:
      from Weimar to Bonn].

PMID- 22590763
TI  - [Discourses and experiences: looking    back on the historiography of the body in
      the 1990's].

PMID- 22590764
TI  - Indications for recombinant human growth hormone and evaluation of available
      recombinant human growth hormone devices: implications for managed care
      organizations.
AB  - There are now many recombinant human growth hormone (rhGH) products and delivery
      devices available for rhGH therapy. Not all products are approved to treat both
      children and adults, and they vary with respect to indications approved by the US
      Food and Drug Administration. Dosing of rhGH is based on weight, and a higher
      dose (per kg) is recommended in children than adults. This approximates the
      normal difference in growth hormone (GH) secretion between these 2 patient
      populations. Patient adherence to treatment is influenced by a number of factors,
      and patient inclusion in treatment decisions, such as the choice of delivery
      device, appears to be important. Unmet expectations are a key issue for many
      patients and families who decide to discontinue treatment. Counseling patients
      and families about predicted adult height with rhGH therapy should be based on
      realistic expectations. Managed care organizations face several challenges in
      providing rhGH therapy, including deciding who is most likely to benefit from
      treatment and when to discontinue treatment if the benefits appear to level off.

PMID- 22590765
TI  - Clinical and humanistic aspects of growth hormone deficiency and growth-related
      disorders.
AB  - Growth hormone (GH) therapy has evolved rapidly since the introduction of
      recombinant human GH (rhGH). The increase in the availability and safety of GH
      therapy has also increased the number of US Food and Drug Administration (FDA)
      indications for use in both children and adults. FDA indications in children
      include GH deficiency (GHD), Turner syndrome, idiopathic short stature, small for
      gestational age with failure to attain normal growth percentiles, Prader-Willi
      syndrome (PWS), chronic renal insufficiency, Noonan syndrome, and short stature
      due to short stature homeobox gene haploinsufficiency. Children and adolescents
      with GHD have demonstrated the greatest response to GHD therapy. The primary
      objective of rhGH therapy in children is to increase height velocity; however,
      the therapy also has benefits related to improved body composition, especially in
      children with conditions like PWS. Treatment of adult GHD primarily targets
      improvements in body composition, quality of life, and surrogate markers for
      cardiovascular disease. The safety reports of rhGH in children are generally
      good, but there have been a small number of cases of raised intracranial
      pressure, scoliosis, and muscle and joint discomfort. In adults, many side
      effects can be managed with dose titration at the initiation of treatment and
      dose reduction if side effects occur.

PMID- 22590766
TI  - [A 1946 list from the Soviet Union of persons  killed in   World War II].

PMID- 22590767
TI  - [Wehrmacht and prostitution:the    German military administration's regulation of
      sexual relations in   occupied    France, 1940-44].

PMID- 22590768
TI  - Issues related to recombinant human growth hormone utilization and optimization
      in a health plan setting.
AB  - Healthcare expenditures in the United States are high and continue to increase;
      as a result, providers and managed care organizations have to evaluate the impact
      of specialty drugs such as recombinant human growth hormone (rhGH) therapy. As
      the number of approved indications for rhGH therapy has increased, so too have
      questions about the appropriate allocation of resources for such therapy. This is
      particularly true for the recent rhGH indications in children with idiopathic
      short stature and those short for gestational age who fail to attain normal
      growth percentiles. With a large increase in the number of children eligible for
      rhGH therapy, questions arise as to whether all eligible children should be
      treated with rhGH, and what are the appropriate length of treatment and optimal
      treatment outcomes. These are important questions for managed care organizations
      who must determine the treatment parameters that produce the best outcomes in
      children. The primary disease burdens of growth hormone deficiency (GHD) in
      adults are the changes in body composition and metabolic parameters, and reduced
      quality of life, all of which are associated with improvements following rhGH
      therapy. In adults, the primary economic burden of GHD is healthcare-related
      costs such as increased hospital days and clinic visits.

PMID- 22590769
TI  - [How does one achieve a natural body? Normalizing the   body in the  German
      nudist movement   around 1900].

PMID- 22590771
TI  - Sins of our fathers: a short history of religious child sacrifice.

PMID- 22590774
TI  - [The Chinese Red Cross Medical Relief    Corps and emergency medical service
      training school].

PMID- 22590775
TI  - [Public policy and organizational developments for    integrating traditional
      Chinese and Western medicine since the   founding of the    People's Republic of
      China].

PMID- 22590776
TI  - [Molecular-biological basics of neuroprotection effects of magnesium].

PMID- 22590777
TI  - Falling on deaf ears? Canadian promotion and Welsh emigration to the prairies.

PMID- 22590778
TI  - "Learning suitable to the situation of the poorest classes": the National Society
      and Wales, 1811-1839.

PMID- 22590779
TI  - Is "competitive" corporatism an adequate response to globalisation? Evidence from
      the Low Countries.

PMID- 22590780
TI  - Health service vendors should work together as a team.

PMID- 22590781
TI  - Fragmenting services leads to suboptimum data analysis.

PMID- 22590783
TI  - Reform forces health insurers to reinvent themselves.

PMID- 22590782
TI  - New diabetes medications drive up costs and stymie formulary design.

PMID- 22590784
TI  - Waiting for economic pressure to force our hand.

PMID- 22590785
TI  - Diagnosis of sleep apnea moves from lab to home.

PMID- 22590786
TI  - Obesity's link to certain cancers puts wellness programs on trial.

PMID- 22590787
TI  - Targeting a cystic fibrosis mutation opens door for personalized treatment.

PMID- 22590788
TI  - Participating in the Medicare eRx Incentive Program.

PMID- 22590789
TI  - Leadership skills in the OR. Part 1. Communication helps surgeons avoid pitfalls.

PMID- 22590790
TI  - Physician leadership and the future of surgical practice.

PMID- 22590791
TI  - Sustainable growth rate repeal: the bandages are running out.

PMID- 22590792
TI  - A heart-to-heart with cardiothoracic surgeon and TV host Dr. Oz.

PMID- 22590793
TI  - State of the states: defining surgery.

PMID- 22590794
TI  - Introduction to the special issue on augmentative and alternative communication.

PMID- 22590795
TI  - Using AAC technology to access the world.
AB  - This paper describes the monumental shift in the nature of augmentative and
      alternative communication (AAC) access that has occurred over the past three
      decades. In its earliest days AAC technology was directed at enabling
      interpersonal face-to-face interactions mainly for persons with physical
      impairment. Contemporary AAC access attempts to mirror the access needs of a
      broader population. Accordingly AAC access to today's mainstream technologies
      expands the focus from interpersonal communication to access of information and
      services over the expanding World Wide Web. With this expanded view comes a new
      range of challenges and opportunities. At the same time AAC has expanded its
      reach to include more people with a wider range of complex communication needs.

PMID- 22590796
TI  - The application of natural language processing to augmentative and alternative
      communication.
AB  - Significant progress has been made in the application of natural language
      processing (NLP) to augmentative and alternative communication (AAC),
      particularly in the areas of interface design and word prediction. This article
      will survey the current state-of-the-science of NLP in AAC and discuss its future
      applications for the development of next generation of AAC technology.

PMID- 22590797
TI  - Access interface strategies.
AB  - Individuals who rely on augmentative and alternative communication (AAC) devices
      to support their communication often have physical movement challenges that
      require alternative methods of access. Technology that supports access,
      particularly for those with the most severe movement deficits, have expanded
      substantially over the years. The purposes of this article are to review the
      state of the science of access technologies that interface with augmentative and
      alternative communication devices and to propose a future research and
      development agenda that will enhance access options for people with limited
      movement capability due to developmental and acquired conditions.

PMID- 22590798
TI  - Supporting the communication, language, and literacy development of children with
      complex communication needs: state of the science and future research priorities.
AB  - Children with complex communication needs (CCN) resulting from autism spectrum
      disorders, cerebral palsy, Down syndrome and other disabilities are severely
      restricted in their participation in educational, vocational, family, and
      community environments. There is a substantial body of research that demonstrates
      convincingly that children with CCN derive substantial benefits from augmentative
      and alternative communication (AAC) in their development of communication,
      language and literacy skills, with no risk to their speech development. Future
      research must address two significant challenges in order to maximize outcomes
      for children with CCN: (1) investigating how to improve the design of AAC
      apps/technologies so as to better meet the breadth of communication needs for the
      diverse population of children with CCN; and (2) ensuring the effective
      translation of these evidence-based AAC interventions to the everyday lives of
      children with CCN so that the possible becomes the probable. This article
      considers each of these challenges in turn, summarizing the state of the science
      as well as directions for future research and development.

PMID- 22590799
TI  - Young adults with complex communication needs: research and development in AAC
      for a "diverse" population.
AB  - A successful transition to adult society requires attention to four major goals:
      (a) have a safe and supportive place to live; (b) participate in meaningful
      activities; (c) maintain access to needed services; and (d) develop friendships
      and intimate relationships. For young adults with complex communication needs
      (CCN), access to augmentative and alternative communication (AAC) plays a
      critical role in the achievement of these valued outcomes. This article discusses
      what is known about the use of AAC to support communication by young adults with
      CCN, and identifies areas for future research and development in AAC technology.

PMID- 22590800
TI  - Current and future AAC research considerations for adults with acquired cognitive
      and communication impairments.
AB  - Adults with acquired language impairments secondary to stroke, traumatic brain
      injury, and neurodegenerative diseases are candidates for communication supports
      outside of the traditional restoration-based approaches to intervention. Recent
      research proves repeatedly that augmentative and alternative communication (AAC)
      provides a means for participation, engagement, conversation, and message
      transfer when individuals can no longer expect full return of pre-morbid
      communication skills and that inclusion of communication supports should begin
      early. We discuss current research and future directions for integrated systems
      of technical supports that include low-technology, high tech, and partner
      dependent strategies for adults with severe and chronic aphasia, cognitive
      communication problems resulting from traumatic brain injuries, and primary
      progressive aphasia.

PMID- 22590801
TI  - Canadian trends in cancer prevalence.
AB  - BACKGROUND: Cancer prevalence trends are rarely reported in the published
      literature, and until now, have not been reported for Canada. DATA AND METHODS:
      Based on incidence data from the Canadian Cancer Registry linked with mortality
      data from the Canadian Vital Statistics Death Database, trends in prevalence
      proportions overtime were calculated by time since diagnosis for a large number
      of the most common cancers. RESULTS: Statistically significant increases in
      prevalence proportions were observed for most individual cancers, and most
      prevalence durations studied. Aging of the population contributed to these
      increases. Relatively large increases were observed for liver and thyroid cancer,
      while decreases occurred for cancers of the larynx and cervix uteri.
      INTERPRETATION: Information on how and why trends vary by cancer can inform
      resource allocation planning.

PMID- 22590803
TI  - Health of First Nations children living off reserve and Metis children younger
      than age 6.
AB  - BACKGROUND: Aboriginal children have been shown to experience poorer health,
      compared with their non-Aboriginal counterparts. Differences in health status may
      be associated with family and social conditions, lifestyle or behaviour, and
      cultural factors. DATA AND METHODS: The current study examined the parent
      /guardian-reported health of First Nations children living off reserve and Metis
      children younger than 6. This does not include the 43% of First Nations children
      who were living on reserves in 2006. Data from the 2006 Aboriginal Children's
      Survey were used to investigate measures of child health and assess possible
      associations with social determinants of health. RESULTS: Most First Nations
      children living off reserve and Metis children were reported to be in excellent
      or very good health. The most common chronic conditions reported by
      parents/guardians were asthma, speech and language difficulties, allergies, and
      lactose intolerance. Several social determinants were associated with child
      health, including parental education, household income, breastfeeding, and
      perceptions of housing conditions and health facilities in the community.
      INTERPRETATION: The findings suggest that social factors can be associated with
      parent-/guardian-rated health of First Nations children living off reserve and
      Metis children under age 6.

PMID- 22590802
TI  - Adopting leisure-time physical activity after diagnosis of a vascular condition.
AB  - BACKGROUND: A better understanding of factors associated with adopting leisure
      time physical activity among people with chronic vascular conditions can help
      policy-makers and health care professionals develop strategies to promote
      secondary prevention among older Canadians. DATA AND METHODS: Cross-sectional
      data from the 1994/1995 National Population Health Survey (NPHS), household
      component, and the 2007/2008 Canadian Community Health Survey were used to
      estimate the prevalence of inactivity. Longitudinal data from eight cycles
      (1994/1995 through 2008/2009) of the NPHS, household component, were used to
      examine the adoption of leisure-time physical activity, intentions to change
      health risk behaviours, and barriers to change. RESULTS: Over half (54%) of the
      population aged 40 or older were inactive during their leisure time in 2007/2008.
      A new vascular diagnosis was not associated with initiating leisure-time physical
      activity. Among the newly diagnosed, those with no disability or a mild
      disability had higher odds of undertaking leisure-time physical activity.
      INTERPRETATION: The majority of Canadians in mid- to late life are inactive. They
      tend to remain so when diagnosed with a vascular condition.

PMID- 22590804
TI  - Sexual behaviour and condom use of 15- to 24-year-olds in 2003 and 2009/2010.
AB  - Based on data from the 2003 and 2009/2010 Canadian Community Health Survey
      (CCHS), this article provides current information about the sexual behaviours and
      condom use of 15- to 24-year-olds and examines changes since 2003. Between 2003
      and 2009/2010, the percentage of 15- to 24-year-olds who had had sexual
      intercourse at least once remained stable, as did the percentages who reported
      becoming sexually active at an early age and having multiple sexual partners.
      Condom use increased between 2003 and 2009/2010, particularly among people
      reporting that they had just one sexual partner.

PMID- 22590805
TI  - Assessment of validity of self-reported smoking status.
AB  - BACKGROUND: Cigarette smoking is associated with adverse health effects,
      including cancer, respiratory illness, heart disease and stroke. National data on
      smoking prevalence often rely on self-reports. This study assesses the validity
      of self-reported cigarette smoking status among Canadians. DATA AND METHODS: Data
      are from the 2007 to 2009 Canadian Health Measures Survey, a nationally
      representative cross-sectional survey of 4,530 Canadians aged 12 to 79. The
      survey included self-reported smoking status and a measure of urinary cotinine, a
      biomarker of exposure to tobacco smoke. The prevalence of cigarette smoking was
      calculated based on self-reports and also on urinary cotinine concentrations.
      RESULTS: Compared with estimates based on urinary cotinine concentration, smoking
      prevalence based on self-report was 0.3 percentage points lower. Sensitivity
      estimates (the percentage of respondents who reported being smokers among those
      classified as smokers based on cotinine concentrations) were similar for males
      and females (more than 90%). Although sensitivity tended to be lower for
      respondents aged 12 to 19 than for those aged 20 to 79, the difference did not
      attain statistical significance. INTERPRETATION: Accurate estimates of the
      prevalence of cigarette smoking among Canadians can be derived from self-reported
      smoking status data.

PMID- 22590806
TI  - Geozones: an area-based method for analysis of health outcomes.
AB  - BACKGROUND: Administrative datasets often lack information about individual
      characteristics such as Aboriginal identity and income. However, these datasets
      frequently contain individual-level geographic information (such as postal
      codes). This paper explains the methodology for creating Geozones, which are area
      based thresholds of population characteristics derived from census data, which
      can be used in the analysis of social or economic differences in health and
      health service utilization. DATA AND METHODS: With aggregate 2006 Census
      information at the Dissemination Area level, population concentration and
      exposure for characteristics of interest are analysed using threshold tables and
      concentration curves. Examples are presented for the Aboriginal population and
      for income gradients. RESULTS: The patterns of concentration of First Nations
      people, Metis, and Inuit differ from those of non-Aboriginal people and between
      urban and rural areas. The spatial patterns of concentration and exposure by
      income gradients also differ. INTERPRETATION: The Geozones method is a relatively
      easy way of identifying areas with lower and higher concentrations of subgroups.
      Because it is ecological-based, Geozones has the inherent strengths and
      weaknesses of this approach.

PMID- 22590807
TI  - Clinical performance of human papillomavirus E6, E7 mRNA flow cytometric assay
      compared to human papillomavirus DNA typing.
AB  - OBJECTIVE: To use flow cytometry to screen cervical samples for the
      overexpression of human papillomavirus (HPV) E6 and E7 mRNA and compare the
      performance of this assay with an HPV DNA array for the detection of high-grade
      cervical lesions. STUDY DESIGN: Cervical samples were analyzed for HPV DNA by
      clinical arrays, and the overexpression of E6 and E7 viral oncogenes was
      monitored using an HPV mRNA detection kit that quantifies the intracellular HPV
      E6 and E7 mRNA on a cell-by-cell basis. RESULTS: HPV positivity increased with
      severity of histologic lesions. On the basis of histology-confirmed CIN 2+ cases
      the specificity of HPV assay was 73.9% (95% CI 66.07, 80.88), whereas it was
      39.3% (95% CI 31.85, 47.1) for the DNA assay. CONCLUSION: The HPV assay provides
      an early predictor of persistent HPV infection and may improve cervical cancer
      screening by increasing the specificity of detecting high-grade lesions.

PMID- 22590808
TI  - Human papillomavirus E6/E7 mRNA testing has higher specificity than liquid-based
      DNA testing in the evaluation of cervical intraepithelial neoplasia.
AB  - OBJECTIVE: To examine the specificity of human papillomavirus (HPV) E6/E7 mRNA
      testing for intraepithelial precursor lesions and invasive carcinoma of the
      uterine cervix in 358 women and compare the results with those of the most widely
      used DNA technique. STUDY DESIGN: For HPV E6/E7 mRNA testing an amplification
      assay was used. For DNA determination a hybridization assay was applied. Both
      techniques were used simultaneously in patients with normal morphology (150),
      cervical intraepithelial neoplasia (173) and invasive carcinoma of the cervix
      (35). RESULTS: HPV DNA positivity rates were significantly higher than E6/E7 mRNA
      in women with normal morphology (21-7%), cervical intraepithelial neoplasia (CIN)
      1 and 2 (75-43%), and CIN 3 (93-63%). In invasive cervical carcinoma, both
      methods tested equally high (94% vs. 97%). Considering that E6/E7 up-regulation
      represents the initial step in cervical carcinogenesis, it can be assumed that
      this test allows a more specific detection of lesions with a potential for
      progression. CONCLUSION: HPV E6/E7 mRNA may serve as a more specific
      discriminator between transient cervical dysplasias and potentially progressive
      lesions. Accordingly, testing for high-risk HPV E6/E7 mRNA might reduce the
      psychologic burden associated with HPV-DNA testing.

PMID- 22590809
TI  - Molecular findings of nasopharyngeal carcinoma in a European population.
AB  - OBJECTIVE: To explore biomolecular characteristics of a group of patients with
      nasopharyngeal carcinoma from European (Spanish) hospitals, addressing the
      pathogenesis of the tumor and the response to treatment. STUDY DESIGN: Cyclin D1
      and p16 expression were evaluated immunohistochemically in 33 tissue samples of
      nasopharyngeal carcinoma. CCDN1 gene amplification and p16 gene deletion were
      studied by fluorescence in situ hybridization. Patient clinical data were
      examined, and tissues were evaluated histologically using hematoxylin-eosin
      staining. RESULTS: Cyclin D1 overexpression was found in 19 cases, and p16
      expression was undetected in 30 cases. An association was observed between
      impaired p16 expression and cyclin D1 overexpression (p = 0.034). Eleven patients
      displayed p16 gene deletion and CCDN1 gene amplification. CONCLUSION: Cyclin D1
      overexpression and CCDN1 amplification, loss of p16 expression and p16 deletion
      may be among the genetic alterations involved in the pathogenesis of
      nasopharyngeal carcinoma.

PMID- 22590810
TI  - Cascaded learning vector quantizer neural networks for the discrimination of
      thyroid lesions.
AB  - OBJECTIVE: To investigate capability of combination of learning vector quantizer
      (LVQ) neural networks (NNs) in discrimination of benign from malignant thyroid
      lesions. STUDY DESIGN: The study included 335 liquid-based cytology, fine needle
      aspiration (FNA), Papanicolaou-stained specimens. All cases were compared to the
      histologic diagnosis. Features describing size, shape, and texture of -100 nuclei
      per case were extracted from cytologic images using a custom image analysis
      system. These features were used to classify each nucleus by LVQ type NNs. The
      nucleus classification results were used to classify individual lesions with a
      second LVQ NN. Cases were distributed by histologic diagnosis. Data from -50%
      from each category were used for training LVQ classifiers. Remaining data were
      used to test classifier performance. The system was used to discriminate to
      individual cellular level and individual patient level between benign and
      malignant nuclei. RESULTS: Application of the proposed algorithm combining two
      LVQ NNs allows discrimination between benign and malignant cell nuclei and
      lesions. CONCLUSION: Results indicate that use of NNs, combined with image
      morphometry, can provide information on thyroid lesion malignancy potential. The
      system could improve FNA diagnostic accuracy of the thyroid gland, especially in
      follicular neoplasms suspicious for malignancy and in Hurthle cell tumors.

PMID- 22590811
TI  - Application of an artificial neural network in the prognosis of chronic myeloid
      leukemia.
AB  - OBJECTIVE: To use a commercially available artificial neural network (ANN)
      software program to distinguish prognostically good and bad cases of chronic
      myeloid leukemia (CML). STUDY DESIGN: A total of 40 patients with CML who
      developed blast crisis or proceeded in the accelerated phase were selected. They
      formed two groups, group 1 and group 2, of 20 patients each, who developed
      accelerated phase or blast crisis within 18 months or 30 months, respectively,
      after the initial diagnosis of the chronic phase of CML. The detailed clinical,
      hematologic, and morphometric data were collected in all these cases. A suitable
      ANN software program was used to analyze these data. RESULTS: All cases were
      randomly distributed automatically by the program into three groups: training set
      (28), validation set (4), and test set (8). In the test set, the ANN program
      successfully classified all group I and group II patients. CONCLUSION: We
      successfully used a commercially available ANN software program to develop a
      model able to classify prognostically good and bad cases of CML.

PMID- 22590812
TI  - Pelvic urothelial carcinoma with nested pattern of growth and an uncommon
      clinical presentation: a case report.
AB  - BACKGROUND: Nested variant of urothelial carcinoma (NVUC) is a rare and often
      unrecognized urothelial neoplasia. Diagnosis is based on morphology only, and no
      immunohistochemical or cytogenetic differences from usual high-grade urothelial
      carcinomas have been reported. CASE: We describe the case of a 49-year-old woman
      affected by hepatitis C virus presented with fever, discomfort, urgency, and
      hypertension. Computed tomography showed a sclerosing inflammatory process
      involving the connective and adipose tissue of the renal sinus. In the absence of
      renal or pelvic masses an underlying malignancy was excluded and renal abscess or
      tuberculosis was suspected. Accordingly, nephrectomy and proximal ureterectomy
      was performed. Grossly, calices, renal pelvis, and pyeloureteral junction
      appeared modestly dilated with whitish, thickened, and uneven mucosa.
      Microscopically, the subepithelial connective tissue, the fibromuscular layer,
      and the renal sinus fat were diffusely infiltrated by small nests of medium to
      large urothelial cells (p63 positive) with abundant eosinophylic cytoplasm and
      slightly atypical nuclei. CONCLUSION: On the basis of morphologic and
      immunohistochemical features, a diagnosis of NVUC was made. After surgery, the
      patient recovered from hypertension. Pelvic and upper urothelial tract NVUCs are
      uncommon, and to the best of our knowledge, this is the second case of NVUC with
      renal involvement.

PMID- 22590814
TI  - Comparative study of oral mucosa micronuclei in smokers and alcoholic smokers.
AB  - OBJECTIVE: To compare the frequency of micronuclei and metanucleated anomalies in
      the oral mucosa of smokers, alcoholic smokers, and nonsmokers. STUDY DESIGN:
      Three groups were studied: group I, 15 smokers; group II, 16 alcoholic smokers;
      and group III, 20 nonsmokers. Three smears from the lateral left border of the
      tongue were processed for Feulgen staining. A minimum of 300 cells per
      participant were examined for the quantification of micronuclei and metanucleated
      anomalies. RESULTS: The Kruskal-Wallis test showed no significant difference in
      the frequency of micronuclei (p = 0.602) or karyorrhexis (p = 0.114) among the
      three groups, but there was a significant difference in the frequency of broken
      eggs, binucleated cells, and karyolysis (p = 0.001). Spearman's correlation
      indicated an influence of the number of cigarettes per day on micronuclei
      frequency. Tobacco caused significant alterations in the exfoliative cytology
      (broken eggs, binucleated cells, and karyolysis) of chronic smokers, but not in
      the frequency of micronuclei or karyorrhexis, despite the observation of a larger
      absolute number of micronuclei in group II. CONCLUSION: The action of genotoxic
      agents (tobacco and alcohol) causes alterations in the frequency of micronuclei
      and metanucleated anomalies.

PMID- 22590813
TI  - Karyometry of nuclear phenotypes in cutaneous squamous cell cancer.
AB  - OBJECTIVE: To establish the karyometric characteristics of the two main nuclear
      phenotypes in cutaneous squamous cell cancer (cSCC) lesions. STUDY DESIGN: The
      clinical materials comprised 75 cases of cSCC, 38 with aggressive lesions and 37
      with nonaggressive lesions. High-resolution images of 100 nuclei per case were
      recorded. Data were partitioned into four subgroups covering the range of lesion
      progression. Four discriminant functions were derived to distinguish aggressive
      from nonaggressive lesions. The most typical nuclei from the phenotype
      predominant in aggressive lesions and nonaggressive lesions were separated out by
      thresholding on the discriminant function score axes. For these homogeneous sets
      of nuclei the karyometric features were computed. RESULTS: The nuclear
      populations in cSCC lesions are a very heterogeneous set. There are two axes of
      dispersion, along the line of lesion progression and between aggressive and
      nonaggressive lesions. The analysis faces the difficulty that lesions from both
      diagnostic categories contain nuclei of the same two phenotypes with the
      difference between categories consisting only of differences in proportion of the
      two phenotypes. CONCLUSION: The nuclei of the aggressive phenotype I and
      nonaggressive phenotype II have substantially different chromatin patterns and
      can be distinguished with > 90% correct recognition rate.

PMID- 22590816
TI  - Evaluation of peritoneal fluid hemosiderin-laden macrophages in biopsy-proven
      endometriosis.
AB  - OBJECTIVE: To evaluate peritoneal fluid hemosiderin-laden macrophages (H-LMs) in
      patients with endometriosis compared to controls. STUDY DESIGN: Consecutive
      series of 46 patients during a year undergoing laparoscopy for benign gynecologic
      conditions were included. The presence of H-LMs in peritoneal fluid was
      evaluated. We compared clinical factors in patients with or without endometriosis
      in respect to H-LM status. To assess the potential of H-LMs to diagnose
      endometriosis, the sensitivity and specificity were calculated. RESULTS: Patients
      with endometriosis were significantly more likely to have positive H-LM test
      results than controls (p = 0.0013). The presence of H-LM has a low sensitivity of
      52% but an acceptable specificity of 87% in diagnosing endometriosis. The
      presence of H-LMs was not related with any other of the clinical factors studied.
      CONCLUSION: The presence of specific findings of H-LMs related to endometriosis
      strongly suggests abnormalities in peritoneal iron metabolism.

PMID- 22590815
TI  - Angiogenetic pathway as a therapeutic target in renal cell carcinoma.
AB  - For several decades, metastatic renal cell carcinoma (mRCC) was considered
      resistant to therapy and thus linked to poor prognosis. Recent years have seen a
      complete revolution of the therapeutic landscape, with the introduction of new
      target therapies that have radically changed treatment strategies in this
      setting. These new agents have proved to be effective if directed mainly against
      the angiogenic pathway. The vascular endothelial growth factor family is, in
      fact, the main target of a number of new drugs, such as monoclonal antibodies and
      different generations of tyrosine-kinase inhibitors that are currently approved
      or in different stages of clinical trial for the treatment of mRCC patients.

PMID- 22590817
TI  - Aberrant connexin 43 and 26 expression in cervical dysplasia.
AB  - OBJECTIVE: To determine whether connexin (Cx) expression is altered in cervical
      dysplasia. STUDY DESIGN: Cx proteins form gap junctions and are expressed in
      squamous epithelia including ectocervix. We used multispectral imaging to perform
      a quantitative immunohistochemical survey of Cx43 Cx26 in 37 archival human
      cervical specimens. RESULTS: Cx43 expression was very low in normal cervix
      (100%), but was increased in low-grade squamous intraepithelial lesions (LSILs)
      (64%), primarily in a parabasal distribution. High-grade squamous intraepithelial
      lesions (HSILs) showed weak full-thickness Cx43 staining (53%) or lacked Cx43
      (47%). An aberrant increase in Cx43 expression was often (62%) present in
      histologically normal areas of specimens that elsewhere harbored dysplasia. Cx26
      was highly expressed in the basal layer of normal ectocervix (100%). In LSIL, 57%
      showed a decrease in Cx26 and the rest showed no change relative to the normal
      pattern. In HSIL, Cx26 was expressed in the full thickness of the epithelium, at
      a high level in 80% of cases and a low level in the rest. CONCLUSION: Cx
      alteration is moderately consistent in cervical dysplasia, and for Cx43 can
      precede histologic changes. The resulting changes in Cx signaling may be
      important in the pathogenesis of cervical intraepithelial neoplasia.

PMID- 22590818
TI  - Hormone receptors expression in phyllodes tumors of the breast.
AB  - OBJECTIVE: To ascertain the hormonal receptor profiles of the epithelial and
      stromal components of phyllodes tumors (PTs) and determine their relationship
      with stromal proliferation. STUDY DESIGN: Eighty-two PTs (50 benign, 22
      borderline, and 10 malignant) were studied. Automated immunohistochemical
      staining for estrogen receptor (ER)-alpha and -beta, progesterone receptor (PR),
      androgen receptor (AR), and Ki-67 was performed using tissue microarray blocks,
      and their expression was assessed in both the stromal and epithelial components.
      RESULTS: The epithelial component demonstrated the expression for ER-alpha
      (45.6%, 36 of 79), ER-beta (37.2%, 29 of 78), PR (91.1%, 72 of 79), and AR
      (10.1%, 8 of 79). The stromal component was positive for ER-beta (29.3%, 24 of
      82) only. The epithelial expression of ER-beta was found to be significantly
      correlated with the epithelial expression of AR (r = 0.352, p = 0.002). No
      association was found between hormone receptor expression and PT tumor grade.
      Stromal Ki-67 expression was statistically correlated with epithelial ER-beta,
      epithelial AR, and stromal ER-beta expression. CONCLUSION: Epithelial and stromal
      ER-beta and epithelial AR expression in PTs was correlated with the proliferative
      rate in the stromal component. Immunohistochemical examination of ER-beta and AR
      may have some impact on the postoperative management of patients with PTs.

PMID- 22590820
TI  - Micronucleus scoring in urine cytology specimen by DNA-specific stain.
AB  - OBJECTIVE: To evaluate the role of micronuclei (MN) scoring in urinary cytology
      of bladder transitional cell carcinoma (TCC). STUDY DESIGN: Eighty cases of
      freshly voided urine samples were used for scoring of MN using acridine orange
      (AO)-stained smears under fluorescence microscope and routine Papanicolaou
      stained smears under light microscopy. MN score for cytologic lesions was
      compared. RESULTS: In AO-stained slides, the mean MN scores were 0.171 +/- 0.395
      and 1.489 +/- 1.871 in smears with "no malignant cells seen" and TCC cases,
      respectively. In Papanicolaou-stained slides the mean MN scores were 0.194 +/-
      0.419 and 1.84 +/- 1.876 in smears with "no malignant cells seen," and TCC cases,
      respectively. Independent sample t test showed significant difference of MN
      scoring in Papanicolaou-stain and AO stain in no malignancy vs. TCC. Pearson's
      correlation test showed strong positive correlation between mean MN score by AO
      and Papanicolaou stains and Pearson's correlation coefficient. CONCLUSION: MN
      score was significantly high in TCC cases, which may be due to chromosomal damage
      in bladder carcinoma. In difficult cases, MN may help distinguish benign from
      malignant cells in urine samples. Routine Papanicolaou stain may also be used for
      MN score because DNA-specific AO-stained smear gives almost similar results.

PMID- 22590819
TI  - Analysis of performance characteristics of five cell cycle-related
      immunohistochemical markers and human papillomavirus genotyping in the diagnosis
      of cervical squamous cell carcinoma precursor lesions.
AB  - OBJECTIVE: To study the performance values of a set of five immunohistochemical
      markers involved in cell cycle regulation as a potential aid in the differential
      diagnosis between squamous intraepithelial lesions (SILs) and normal or benign
      conditions of the uterine cervix. STUDY DESIGN: Results from immunohistochemical
      evaluation of p16, cyclin D1, p53, Ki67, and ProEx C markers and human
      papillomavirus genotyping were collected from a previous study performed on 37
      normal or benign cervices, 39 low grade SILs and 73 high grade SILs. A
      multivariate analysis was used to examine the specific diagnostic value of each
      marker and to ascertain those most relevant for SIL diagnosis. For markers with
      good data fit, sensitivity, specificity, accuracy, area under the receiver
      operating characteristic curve, and integrated discrimination improvement, were
      calculated. RESULTS: Among individual markers, ProEx C showed the best
      specificity; p16 displayed the highest sensitivity and area under receiver
      operating characteristic curve for SIL diagnosis. Integrated discrimination
      improvement demonstrated that the p16 plus ProEx C model has better
      discrimination capacity than p16 plus Ki67 or ProEx C plus Ki67. CONCLUSION: Use
      of ProEx C alone or in combination with p16 could provide useful information for
      SIL diagnosis.

PMID- 22590821
TI  - Cross-functional support ensures success.
AB  - A comprehensive PPE program that has the support of key stakeholders at the
      corporate and plant levels has the potential to yield significant safety,
      productivity, and cost improvements. An automotive manufacturer, for example, was
      able to decrease injuries by 70 percent and reduce SKUs 24 percent by
      implementing recommendations resulting from a comprehensive PPE program that had
      the endorsement of key safety, procurement, operations, and production personnel
      from the start. Gaining cross-functional commitment for a comprehensive PPE
      program not only will move the improvement process forward, but also will ensure
      the company benefits from optimal cost and performance advantages that positively
      impact the bottom line.

PMID- 22590822
TI  - Technology to the rescue.

PMID- 22590823
TI  - Caring for your greatest asset.

PMID- 22590824
TI  - Solving vehicle fall hazards.

PMID- 22590825
TI  - My feet are killing me!

PMID- 22590826
TI  - Stop making it difficult to be excellent in safety.

PMID- 22590827
TI  - OSHA in health care: out of sight & out of mind?

PMID- 22590828
TI  - Make your move: weave exercise into the work day.

PMID- 22590829
TI  - What is first aid? What is first aid training?

PMID- 22590830
TI  - IAQ and occupational asthma.

PMID- 22590831
TI  - The practice of leadership.

PMID- 22590832
TI  - AT1 receptors activation enhances the expression of MMP-2, MMP-13 and VEGF but
      not MMP-9 in B16F10 melanoma cells.
AB  - Melanoma is one of the most aggressive cancers of all solid tumors. The effect of
      angiotensin II on expression of three Matrix Metalloproteinases (MMPs) and
      Vascular Endothelial Growth Factor (VEGF) in B16F10 melanoma cells was evaluated.
      Also the blocking effect of losartan on angiotensin II induced effects was
      assessed. B16F10 murine melanoma cells were cultured in RPMI-1640 medium
      supplemented with 10% Fetal Bovine Serum (FBS) and 24 h prior to experiment the
      serum free medium was used. Angiotensin II (0 M, 10(-10) M, 10(-9) M or 10(-8) M)
      alone or in combination with Losartan (10(-6) M) in RPMI-1640 replaced the medium
      for experiments. After the incubation time (0, 1, 2, 6 and 12 h) cells were
      harvested using 0.05% (w/v) Trypsin and then recovered by centrifugation. The
      expression of MMP-2, MMP-13, MMP-9 and VEGF in B16F10 cell lysate was assessed by
      immunoblotting. Angiotensin II significantly enhanced the expression of MMP-2,
      MMP-13 and VEGF by concentrations as low as 0.1 nM. But angiotensin II could not
      stimulate any significant increase in MMP-9 expression by angiotensin II in
      B16F10 cells. Losartan abolished the enhancing effect of every concentration of
      angiotensin II on MMP-2, MMP-13 and VEGF expression completely and in all
      incubation times. As a result, angiotensin II through activation of AT1 receptors
      can stimulate the expression of MMP-2, MMP-13 and VEGF in B16F10 melanoma cells.
      This is an important conclusion because of the importance of these factors in
      melanoma invasiveness and the possible important role that angiotensin receptor
      blockers may play as cancer medications.

PMID- 22590833
TI  - The correlation of genetic diversity and geographic distribution of Fusarium
      graminearum in North part of Iran.
AB  - Fusarium Head Blight (FHB), caused mainly by Fusarium graminearum, is one of the
      most notorious diseases in North part of Iran. Due to lack of sufficient
      information regarding genetic diversity of FHB, the correlation between genetic
      diversity and geographic distribution of 52 isolates that collected from infected
      wheat kernels from four main grown region of North part of Iran were analyzed
      with 10 simple Sequence Repeat (SSR) primers and 15 Random Amplified Polymorphic
      DNA (RAPD) primers. The un-weighed pair group method using arithmetic means
      (UPGMA) was used and a dendrogram was constructed based on Jaccard's similarity
      coefficient. Principal Component Analysis (PCA) of SSR and RAPD markers revealed
      that the first two factors accounted for 51 and 41% of the total variance,
      respectively. SSR and RAPD data classified isolates into four and seven groups,
      respectively. SSR analysis showed that there was a correlation between genetic
      clusters of isolates and geographical origin in F. graminearum. However, results
      of cluster analysis using RAPD data didn't show any relation with geographical
      distribution but the results of this analysis confirmed a genetic variation among
      all isolates.

PMID- 22590834
TI  - Phylogenetic study on nonstructural (NS) gene of H9N2 isolated from broilers in
      Iran during 1998-2007.
AB  - Since 1998, H9N2 AI outbreaks have been one of the major problems in Iranian
      poultry industry. The association of high mortality and case report of H5N1 and
      H9N2 influenza virus in wild birds in recent years raised the specter of a
      possible new genetic modified AI virus. In this study, we do phylogenetic
      analysis on Full- length Nonstructural (NS) genes of seven H9N2 Isolates from
      Broilers in Iran, Tehran province during 1998-2007. Phylogenetic analysis clearly
      shows that Iranian H9N2 isolates gene pools, corresponding to just NS allele A.
      Comparison of nucleotide sequences of isolated viruses revealed a substantial
      number of silent mutations, which results in high degree of homology in amino
      acid sequences. In addition, the cluster of Iranian H9N2 isolates could be
      subdivided into two subgroups, which matched their times of isolation especially
      around 2006 time line. The high degree of similarity between the NS genes of the
      Iranian H9N2 isolates supports the hypothesis that these genes originated from a
      single predecessor. Present result provides useful molecular epidemiological data
      to understand the dynamics of H9N2 evolution during 9 years in Iran and support
      earlier phylogenetic observations.

PMID- 22590835
TI  - Common carotid artery intima-media thickness and atherosclerotic plaques in
      carotid bulb in patients with chronic kidney disease on hemodialysis: a case
      control study.
AB  - The Common Carotid artery Intima-Media Thickness (CCIMT) can reflect systemic
      atherosclerosis in renal patients on hemodialysis. This study aimed to compare
      CCIMT measured by color Doppler ultrasonography between two groups including
      dialytic patients and normal subjects. In this case-control setting, 48 patients
      with Chronic Kidney Disease (CKD) on hemodialysis (case group) and 46 age and sex
      matched healthy subjects (control group) were enrolled in this study. Color
      Doppler ultrasound was used to measure CCIMT and determine presence of
      atherosclerotic plaques in carotid bulb in both groups. Various laboratory
      parameters were also determined. Serum levels of triglyceride, total cholesterol,
      low-density lipoprotein, fasting sugar, ionized calcium, inorganic phosphorus and
      magnesium were comparable between the two groups. Hypertension and elevated
      levels of serum C-reactive protein, as well as the mean levels of serum non
      fasting homocysteine and phosphate were significantly higher in the case group.
      Mean levels of serum high-density lipoprotein and albumin were significantly
      higher in the controls. Mean maximum CCIMT was significantly higher in the case
      group than in controls (0.73 +/- 0.15 vs. 0.68 +/- 0.08 mm, p = 0.01) even after
      adjusting for other confounding variables. Frequency of patients with
      atherosclerotic plaques in carotid bulbs was not significantly different between
      case and controls. In conclusion, this study showed that CCIMT is significantly
      higher in CKD patients on hemodialysis comparing with matched normal
      counterparts. Furthermore, this difference was independent of other conventional
      risk factors for atherosclerosis.

PMID- 22590836
TI  - Independent predictors of in-hospital re-bleeding, need of operation and
      mortality in acute upper gastrointestinal bleeding.
AB  - Prediction of outcome is difficult in patients with acute upper gastrointestinal
      bleeding (AUGIB). Some factors have been proposed in this regard with varying
      accuracy. This study aimed to investigate probable predictors of in-hospital
      outcome in patients with AUGIB. One hundred sixty four patients with AUGIB were
      studied prospectively in Tabriz Imam Reza Teaching Centre. All these patients
      were evaluated endoscopically by an expert. Patients' age, gender, presenting
      complains, transfusion, clinical findings and previous medical history were
      compared between survived vs. expired, re-bled vs. non re-bled and operated vs.
      non operated patients. There were 117 males and 47 females with the mean age of
      57.12 +/- 17.32 (range: 32-78) years in this study. Hematemesis was the sole
      independent predictor of in-hospital mortality (82.1 vs. 100%; p < 0.001). In
      univariate analysis, however, female gender, major hemorrhage and previous
      neurological disease were associated with higher rate of expiration. Comparing
      two re-bled and non re-bled groups, hematemesis (76.5 vs. 95.9%; p = 0.003) and
      need of transfusion > 2U (36.1 vs. 71.4%; p = 0.006) were independent predictors
      of re-bleeding. In univariate analysis, hematocrit < 30%, major hemorrhage and
      previous history of hepatic disease or hypertension were predictive of re
      bleeding. In comparison between operated and non operated groups no significant
      predictor was detected. In conclusion, this study showed that presence of
      hematemesis at the time of admission and need of transfusion > 2U were
      independent predictors of poor outcome in patients with AUGIB.

PMID- 22590837
TI  - Influence of Nigella sativa fixed oil on some blood parameters and histopathology
      of skin in staphylococcal-infected BALB/c mice.
AB  - Nigella sativa has been used for a long time in Jordanian folk medicine to treat
      skin diseases like microbial infections and inflammation. Therefore, the present
      study was conducted to assess the healing efficacy of petroleum ether extract of
      Nigella sativa seeds (fixed oil) on staphylococcal-infected skin. Male BALB/c
      mice were infected with 100 microL of Staphylococcus aureus (ATCC 6538)
      suspension at a dose of 10(8) colony forming unit/mouse into shaved mild dorsal
      skin. Application of treatments for each group (100 microL sterile saline, 100
      microL chloramphenicol (10 microg/mouse) and Nigella sativa fixed oil at a dose
      of 50, 100 or 150 microL/mouse) was performed at the site of infection twice a
      day for two consecutive days after 3 h of infection. At day 3 and 5 after
      infection, total White Blood Cells (WBCs) count; differential and absolute
      differential WBC counts and the number of viable bacteria present in the skin
      area were measured. At day 5 after infection, the animals were sacrificed and the
      histology of skin was examined. Results indicated that fixed oil of Nigella
      sativa seeds enhance healing of staphylococcal-infected skin by reducing total
      and absolute differential WBC counts, local infection and inflammation, bacterial
      expansion and tissue impairment. These effects provide scientific basis for the
      use of Nigella sativa in traditional medicine to treat skin infections and
      inflammations.

PMID- 22590838
TI  - Metformin as an adjunct to insulin for glycemic control in patients with type 2
      diabetes after CABG surgery: a randomized double blind clinical trial.
AB  - Perioperative hyperglycemia is common in patients with type 2 diabetes undergoing
      Coronary Artery Bypass Graft (CABG) surgery and there is a direct relation
      between postoperative hyperglycemia and mortality rate in these patients. The aim
      of the present study is to determine the efficacy of metformin on glycemic
      control in diabetic patients after CABG surgery. In a randomized double blind
      clinical trial, 100 patients with type 2 diabetes admitted in open heart ICU
      after CABG surgery in Mazandaran Heart Center were enrolled. They were randomly
      assigned to two intervention and control groups. Three hours after extubation,
      therapeutic antiglycemic regimens were applied in these two groups and continued
      for three days. Intervention group received regular insulin infusion along with
      two metformin 500 mg tablets per twelve hours while control group received
      regular insulin infusion with two placebo tablets per twelve hours. Blood glucose
      level and other parameters were measured and recorded in determined intervals. To
      analyze the data, independent T-test, paired T-test, Mann-Whitney and repeated
      measure ANOVA tests were employed. Mean blood glucose level was not significantly
      different in the two groups at the beginning of the ICU admission; however, mean
      glucose level in insulin-metformin group, twelve hours after the initiation of
      the study, was significantly lower than insulin group (p < 0.05). In addition,
      mean doses of potassium and insulin demand as well as mean number of episodes of
      hyperglycemia, hypoglycemia and glucose levels out of the accepted range were
      significantly lower in insulin-metformin group (p < 0.05). Alterations in mean
      levels of lactate, BE, pH and creatinine were not statistically significant in
      these two groups. It seems that adding metformin to insulin leads to a better
      glycemic control in type two diabetic patients undergoing CABG surgery without
      causing metabolic acidosis. Therefore, it might be a potential option in blood
      glucose control protocol in this group of patients.

PMID- 22590839
TI  - Selenium supplementation reduced oxidative stress in diethylnitrosamine-induced
      hepatocellular carcinoma in rats.
AB  - Selenium in the form of sodium selenite (SSE) is an essential micronutrient which
      known to possess antioxidant and anticancer properties. This study emphasizes the
      role of selenium on oxidative stress in experimental rats with N
      diethylnitrosamine (DEN) initiated and 2-acetylaminofluorene (2-AAF) promoted
      multistage hepatocellular carcinogenesis (HCC). Rats were divided randomly into
      six groups: negative control, positive control (DEN+2-AAF), preventive group (pre
      SEE 4 weeks+DEN), preventive control (respective control for preventive group),
      therapeutic group (DEN+post-SSE 12 weeks) and therapeutic control (respective
      control for therapeutic group). SSE (4 mg L(-1)) was given to animals before
      initiation and during promotion phase of HCC. The levels of total protein (TP),
      conjugated diens (CD), malondialdehyde (MDA), fluorescent pigment (FP),
      antioxidant activity (AOA) and DNA damage were measured. Supplementation of SSE
      before the initiation phase of carcinogenicity significantly increased TP and AOA
      level (p < 0.05) while it decreased the levels of CD, MDA, DNA damage and FP (p <
      0.05). Supplementation of SSE during the promotion phase of carcinogenicity
      significantly decreased the DNA damage and FP level (p < 0.05) and there were
      negative correlation between the level of AOA and with the level of FP and CD.
      Thus, supplementation of SSE reduced the adverse changes which occur in liver
      cancer. However, the chemoprevention effect of SSE was more pronounced when it
      was supplemented before initiation phase of cancer when compared to promotion
      phase.

PMID- 22590840
TI  - Study on pre-laying characteristics of three breeds of commercial layers in the
      Derived Savannah zone of Nigeria.
AB  - This experiment was conducted to study the effect of strains on productive
      characteristics of three genotypes of commercial pullets: Isa Brown, Bovan Nera
      and Dominant Black. A total number of 300 day-old chicks (100 chicks per strain)
      were purchased from local hatcheries. Individual body weight and linear
      measurements were determined from 0-20 weeks of age. There were highly
      significant (p < 0.01) strain differences in body weight, body length, thigh
      length, shank length, breast girth, feed conversion and feed efficiency. Bovan
      Nera recorded highest body weight, lowest feed conversion ratio and superior feed
      efficiency at maturity (20th week). Dominant Black on the other hand had lowest
      body weight, highest feed conversion and very low feed efficiency while Isa Brown
      recorded intermediate mean values for these traits. It was indicated in this
      study that regardless of strain, all the traits studied increased in mean values
      with advancing age of the birds. In addition, positive association between body
      weight and sexually maturity was established as Bovan Nera with the highest body
      weight at 20th week laid the first egg. The results also revealed the inverse
      relationship between feed conversion and feed efficiency. The former declined in
      mean values as the birds grew older while the latter increased simultaneously but
      the rate of change differs among strains. Bovan Nera was adjudged good and feed
      efficient because the strain had the highest mean values in body weight and feed
      efficiency ratio at maturity (20th week) and could be recommended to farmers for
      increased productivity, income generation and business sustainability.

PMID- 22590841
TI  - The study of antinociceptive effect of hydroalcoholic extract of Teucrium
      oliverianum (a plant used in southern Iranian traditional medicine) in rat by
      formalin test.
AB  - OBJECTIVE: Antinociceptive and anti-inflammatory activities of hydroalcoholic
      extract of Teucrium Oliverianum were investigated by formalin test model. This
      study was conducted in on the male Wistar rats, weighting 150-180 g. The animals
      were divided into seven groups (n = 7) and received 200, 400, 600 and 800 mg kg(
      1) of hydroalcoholic extract of teucrium oliverianum intraperitoneally,
      respectively. Negative control group received normal saline (5 mL kg(-1)) and the
      positive control groups received 2.5 mg kg(-1) morphine and 300 mg kg(-1)
      aspirin, intraperitoneally respectively. The results showed that all doses of
      extract have significant analgesic effect (p < 0.05) in all studies times in
      comparison with negative control. The best result achieved with 600 mg kg(-1) of
      extract. The result revealed that the analgesic effect of the extract (600 mg kg(
      1)) ?was less than aspirin (300 mg kg(-1)) on the second phase of pain and less
      than morphine (2.5 mg kg(-1)) in both phases of the pain, more than aspirin in
      first phase of pain. One group of animals was treated with naloxone (1 mg kg(-1),
      i.p.) and suitable dose of extract (600 mg kg(-1), i.p.). Also, Naloxone
      inhibited analgesic effect of alcoholic extract of Teucrium Oliverianum. It can
      be concluded that the alcoholic extract of Teucrium oliverianum may exert its
      effect through opioid receptors, stimulating GABAergic system or promotes the
      release of endogenous opipeptides or decreasing free radicals.

PMID- 22590842
TI  - Lentinus sp. RJ-2 mushroom is important source of natural antioxidative
      polysaccharides.

PMID- 22590843
TI  - Herbal remedies: a good source of treatment against fungal skin infections.

PMID- 22590844
TI  - Seed extract of Punica granatum possesses antioxidant and antiulcer potential.

PMID- 22590845
TI  - A call for the initiation of a national environmental health network.

PMID- 22590846
TI  - Bacterial amplification and in-place carpet drying: implications for category 1
      water intrusion restoration.
AB  - The study described in this article investigated whether in-place carpet drying
      processes resulted in bacterial amplification following water intrusion from a
      clean water source (category 1) in a residential indoor environment. Bacterial
      amplification was examined after wetting a 10-year-old carpet and pad that had no
      history of water intrusion. Three test areas were extracted and dried using
      industry-recommended procedures for in-place drying and compared to a control
      area that was not extracted or dried. Results from carpet, pad, and subsurface
      dust demonstrated that bacterial amplification occurred in all test areas. CFUs
      of bacteria per gram of carpet surface dust and subsurface dust prior to water
      intrusion were lower than levels in subsurface dust after in-place drying. The
      authors' study contributes to information regarding the restoration of water
      based carpet damage by professional water damage restoration companies, building
      maintenance personnel, and housekeeping managers. Results suggest that the
      appropriate response time for carpet pad salvage is considerably shorter than the
      current industry recommendation of 72 hours.

PMID- 22590847
TI  - 2005 hurricane surveillance: measures to reduce carbon monoxide poisoning in all
      Floridians.
AB  - The 2005 Florida hurricanes caused widespread power outages, increasing generator
      use that directly resulted in a surge in carbon monoxide (CO) poisonings. Of the
      126 CO poisonings documented, 77% were related to generator use and 43% of these
      generators were placed outside but near a window. African-Americans and Latinos
      had a higher incidence of CO poisoning. The strength of the authors' study
      described here was the inclusion of the first responder network in one
      surveillance system for hurricane response. Notable advances have occurred since
      the authors' study, including CO poisoning listed as a reportable condition,
      regulation requiring CO detectors, CO generator warning labeling, and the
      development of a local surveillance and classification program for the county
      health departments. To prepare for future multiple hurricane seasons,
      comprehensive outreach should be focused at the local level through the first
      responder network and community groups to reduce CO poisonings in all
      populations.

PMID- 22590848
TI  - Occupational and environmental exposures among Alaska Native and American Indian
      people living in Alaska and the Southwest United States.
AB  - Most occupational and environmental research describes associations between
      specific occupational and environmental hazards and health outcomes, with little
      information available on population-level exposure, especially among unique
      subpopulations. The authors describe the prevalence of self-reported lifetime
      exposure to nine occupational and environmental hazards among 11,326 American
      Indian and Alaska Native (AI/AN) adults enrolled in the Education and Research
      Towards Health (EARTH) Study in the Southwest U.S. and Alaska. The top three
      hazards experienced by AI/AN people in Alaska were petroleum products, military
      chemicals, and asbestos. The top three hazards experienced by AI/AN living in the
      Southwest U.S. were pesticides, petroleum, and welding/silversmithing. The study
      described here found that male sex, lower educational attainment, AI/AN language
      use, and living in the Southwest U.S. (vs. Alaska) were all associated with an
      increased likelihood of hazard exposure. The authors' study provides baseline
      data to facilitate future exposure-response analyses. Future studies should
      measure dose and duration as well as environmental hazards that occur in
      community settings.

PMID- 22590849
TI  - The burden of environmental disease in the United States.

PMID- 22590850
TI  - Model Aquatic Health Code (MAHC) and International Swimming Pool and Spa Code
      (ISPSC).

PMID- 22590851
TI  - 28 major trends for 2012 and beyond: Part 2.

PMID- 22590852
TI  - Coupling environmental health to public safety.

PMID- 22590853
TI  - [Road map for transmission interruption of schistosomiasis in China].
AB  - Based on the transmission status of schistosomiasis in People's Republic of
      China, the challenges and road map for achieving the transmission interruption of
      schistosomiasis by 2020 in the country was discussed, particularly focused on
      elimination strategy, surveillance and response approaches, and key technique
      needs in the three stages, e.g. pre-elimination, elimination and post-elimination
      stages. Recommendation of strengthening studies on transmission threshold and
      technological innovation at the low transmission level of schistosomiasis
      japonica were put forward.

PMID- 22590854
TI  - [Surveillance and forecast of Schistosoma japonicum-infected sentinel mice in key
      water regions of China in 2010].
AB  - OBJECTIVE: To explore the approach and tool for surveillance and forecast of
      schistosomiasis, so as to provide scientific evidence for improving the
      sensitivity of the surveillance and forecast system of schistosomiasis. METHODS:
      Two field detections were carried out in June and September by using the
      determination of sentinel mice in key high-risk water regions of 7 provinces of
      Hunan, Hubei, Jiangxi, Anhui, Jiangsu, Yunnan and Sichuan, and the sentinel mice
      were raised in laboratory and dissected for observation of schistosome
      infections. The database regarding schisosome infections in key water regions of
      China was established, and the tempo-spatial distribution and environmental
      features of the national surveillance and forecast sites with positive sentinel
      mice were analyzed. RESULTS: A total of 72 surveillance and forecast sites were
      detected in 34 counties (cities, districts) of 7 provinces. Of the 2 667 sentinel
      mice placed, 2 613 were recovered, with a recovery rate of 97.98%. Among the 72
      sites detected, 17 were detected with positive sentinel mice, and the occurrence
      rate of positive sites was 23.61%. The occurrence rate was 17.24% (10/58) in June
      and 14.71% (10/68) in September, and no significant difference was observed
      between two batches (chi2 = 0.151, P = 0.698). Of the 2 436 sentinel mice
      dissected, 90 were positive, and 459 schistosome worms were collected, with a
      total infection rate of 3.69%, and the mean worm burdens of positive mice were
      5.10 worms per mouse. The infection rate of sentinel mice was 2.82% (31/1 099) in
      June and 4.41% (58/1 337) in September, the infection rate of sentinel mice was
      significantly higher in September than that in Juen (chi2 = 14.681, P < 0.01),
      and the mean worm burdens of infected sentinel mice were 2.45 worms per mouse in
      June and 6.49 worms per mouse in September. The occurrence rates of the positive
      sites with infected snails detected in the study year, last year and without
      infected snails detected in recent 3 years were 29.63%, 41.67% and 12.12%,
      respectively, and no significant differences were detected (chi2 = 5.227, P =
      0.071). The infection rates of sentinel mice in the aforementioned 3 settings
      were 9.38%, 3.98% and 0.59%, respectively, and there was significant difference
      observed (chi2 = 20.489, P < 0.01). CONCLUSIONS: The monitoring results of
      sentinel mice infections in key water regions can almost reflect the endemic
      situation of schistosomiasis in local areas. Notably, many infections are
      detected in settings without infected snails detected in recent years. The
      monitoring of sentinel mice infections could significantly improve the
      sensitivity of the surveillance and forecast system of schistosomiasis.

PMID- 22590855
TI  - [Burden of disease in Schistosomiasis japonica. IV. Community socioeconomic
      determinants of chronic schistosomiasis].
AB  - OBJECTIVE: To explore the socioeconomic determinants of chronic schistosomiasis
      japonica at a community (village) level. METHODS: The socioeconomic and
      epidemiological data (Years lived with disability, YLDs) came from the thematic
      research carried out in two schistosome-endemic counties, Dangtu and Hanshou, in
      lake areas between 2004 and 2005. A concentration index was calculated and used
      to assess the health inequalities between socioeconomic statuses. The community
      risk factors relating to chronic schistosomiasis were explored by the multiple
      regression model. RESULTS: The concentration index was -0.12 of Dangtu County and
      0.03 of Hanshou County which indicated that there were no health inequalities due
      to schistosomiasis between communities with different socioeconomic statuses.
      There was no linear relationship between the economic levels and YLDs of chronic
      schistosomiasis. The results of multiple regression model showed that the
      distance from village to schistosome-infested water (P < 0.01) and wet land area
      per capita (P < 0.05) were significantly related to YLDs of chronic
      schistosomiasis. CONCLUSION: There is non-linear relationship between
      socioeconomic levels and YLDs of chronic schistosomiasis, but the distance from
      village to schistosome-infested water and wet land area per capita are
      significantly related to the latter.

PMID- 22590856
TI  - [Establishment and application of spatio-temporal model of schistosomiasis
      japonica in a county in marshland region].
AB  - OBJECTIVE: To develop a spatio-temporal model of schistosomiasis japonica based
      on Bayesian model, and to analyze the spatio-temporal pattern of schistosomiasis,
      as well as to evaluate the impact of environment changes on schistosomiasis
      endemic. METHODS: Different Bayesian models were established by employing the
      data of the periodical surveillance on schistosomiasis during 1996-2005 period by
      taking into account of the uncertainty in sensitivity and specificity of
      diagnostic test, then the best fitness model was selected to analyze the spatio
      temporal pattern of schistosomiasis and evaluate the impact of environment
      changes on schistosomiasis. RESULTS: The model with space-time interaction was a
      better fitting model. No significant temporal correlation was found in human
      infection rate of Schistosoma japonicum, and the difference of spatial structure
      between human infection rates of each year was significant. The prediction map of
      S. japonicum infection showed the changes of infection in the south areas of the
      Yuan River were not significant, while the prevalence increased significantly in
      the north areas of the river, which indicated that the impact of the
      implementation of project on partial abandon areas for water storing on
      prevalence of S. japonicum was stronger than that of the project on completed
      abandon areas for water storing. CONCLUSIONS: It is feasible to develop the
      spatio-temporal model of schistosomiasis japonica based on Bayesian model, and
      this inetegrated Bayesian model approach may become a powerful and statistically
      robust tool for estimating and evaluating the control strategy.

PMID- 22590857
TI  - [Surveillance of schistosomiasis in Sichuan Province, 2005-2010].
AB  - OBJECTIVE: To understand the epidemic trend of schistosomiasis in Sichuan
      Province so as to provide the evidence for formulating schistosomiasis control
      strategy. METHODS: According to the National Schistosomiasis Surveillance
      Protocol, the national surveillance sites in Sichuan Province were selected. The
      schistosomiasis surveillance was carried out continuously from 2005 to 2010.
      RESULTS: Nine national schistosomiasis surveillance sites were established in
      Pujiang, Guanghan, Zhongjiang, Fucheng, Dongpo, Danling, Renshou, Xichang and
      Dechang counties. The Oncomelania hupensis snail area decreased from 351 853 m2
      in 2005 to 128 285 m2 in 2010, the snail density from 0.70 to 0.21 per 0.1 m2,
      the snail infection rate from 0.06% to 0, the positive rate of human serum
      schistosome antibody from 19.41% to 7.62%, the schistosome infection rate of
      human population from 1.93% to 0.10%, and the infection rate of livestock from
      4.50% to 1.02%. The snails were found mainly in ditch, rice field and other moist
      field. CONCLUSIONS: Though the endemic of schistosomiasis has reached a low level
      in Sichuan Province, the endemic situation fluctuates at a narrow range in some
      surveillance sites. Therefore, the surveillance work should be carried out
      continuously.

PMID- 22590858
TI  - [Toxicity test of Luokuwei on mice].
AB  - The result of toxicity test of Luokuwei to mice showed that, when the dose of the
      drug was 400-1 200 times of molluscicidal dosage, the mortality rate of mice was
      only 10%-20% in 24 h, and in 14 d, only the mortality rate in high doasage group
      was above 50%. It is suggested that Luoweiku is a molluscicide with low toxicity.

PMID- 22590859
TI  - [Effect evaluation of transmission control of schistosomiasis in 14 counties
      (cities, districts) of Jiangsu Province].
AB  - OBJECTIVE: To assess the control effect of transmission control of
      schistosomiasis in 14 counties (cities, districts) of Jiangsu Province. METHODS:
      According to the requirement of the national assessment scheme of
      schistosomiasis, the effect of schistosomiasis control was evaluated. The
      schistosomiasis morbidity and changes in Oncomelania snail status in recent 2
      years were assessed. The field survey was done by using the stratified sampling
      method. A heavy-endemicity administrative village was randomly sampled from the
      townships with low, moderate and heavy endemicities in each county, respectively
      as the assessment villages. The morbidity in resident populations and free
      grazing domestic animals and the snail infections in the settings where snails
      were detected and frequent human and domestic animal activities were observed in
      recent 3 years. RESULTS: During the period from 2007 through 2010, the
      transmission control effect of schistosomiasis was assessed in 14 counties
      (cities, districts) of Jiangsu Province, and field surveys were performed in 42
      villages of 39 townships. A total of 264 settings, 1 679.73 hm2 and 39 894 frames
      were surveyed, and 2 179 snails were collected. Of the 405 living snails
      dissected, no infected snails were detected, and the snail infection rate was 0.
      Totally 22 147 residents were investigated. The serum examination of schistosome
      infection was performed in 22 147 residents, and 300 were sero-positive, with a
      sero-positive rate of 1.35% (0.30%-4.26%). The stool examination was done in 297
      sero-positive cases, and no cases were stool-positive, with a stool-positive rate
      of 0. A total of 2 931 domestic animals were investigated, including 230 head of
      cattle, 2 333 pigs and 368 sheep, and no infections were detected. The files
      regarding the schistosomiasis morbidity and snail status have been established in
      14 counties (cities, districts). All infected snails were killed in the 14
      counties (districts, cities) 2 years prior to the assessment, and the mean time
      that no infected snails were detected was 2.71 years (2-4 years). No acute
      schistosomiasis patients were found in all 14 counties (districts, cities) more
      than 3 years prior to the assessment. CONCLUSION: According to the Criteria for
      Control and Elimination of Schistosomiasis in China (GB 15976-2006), the
      transmission of schistosomiasis in 14 countries (cities, districts) of Jiangsu
      Province has been controlled.

PMID- 22590860
TI  - [Correlation between acute schistosomiasis japonica and serum interleukin-33
      levels].
AB  - OBJECTIVE: To study the function of interleukin-33 (IL-33) in the development of
      human acute schistosomiasis japonica by determining the serum IL-33 levels in
      acute schistosomiasis japonica patients. METHODS: Four patients with acute
      schistosomiasis japonica were recruited from schistosomiasis endemic lake areas,
      and 15 controls were recruited outside the schistosomiasis endemic areas. The
      demographic data and venous blood were collected from all the subjects. The serum
      IL-33 levels of all the subjects were tested by using enzyme-linked immunosorbent
      assay. All the results were statistically analyzed with Stata 10.0 software.
      RESULTS: The serum IL-33 levels of the patients with acute schistosomiasis
      japonica [517.33 (334.65, 1 056.88) pg/ml] were significantly higher than those
      of the controls [1.66(1.66, 6.35) pg/ml] (Z = -3.207, P = 0.001). The correlation
      coefficients between serum IL-33 levels and numbers of eosinophils, serum IL-33
      levels and duration of infection were both 0.8 (P = 0.2). CONCLUSIONS: The serum
      IL-33 level is significantly elevated in the patients with acute schistosomiasis
      japonica, indicating that IL-33 may play a pro-inflammatory role in the acute
      stage of schistosomiasis japonica and participate in initiating the Th2 type
      immune responses between 7 and 9 weeks after the infection.

PMID- 22590862
TI  - [Studies on dynamic changes of proportions of Tc1 and Tc2 cells during
      Schistosoma japonicum infection].
AB  - OBJECTIVE: To observe the dynamic changes of the proportions of T cytotoxic type
      1 (Tc1) cells and T cytotoxic type 2 (Tc2) cells and analyze the correlation of
      them with the dynamic changes of the proportions of Th1 and Th2 cells in T
      lymphocytes respectively at different stages after Schistosoma japonicum
      infection. METHOD: Splenocytes were prepared from spleens of mice with S.
      japonicum infection at different stages (0, 3, 5, 8, 13 weeks), and the
      proportions of Tc1, Tc2 and Th1, Th2 cells in T cells were determined by FACS,
      respectively. RESULTS: Compared to the control group (0 week), the proportions of
      Tc1 cells significantly increased 3, 5, 8, 13 weeks post-infection (all P values
      < 0.01) and the proportions of Tc2 cells at different stages (5, 8, 13 weeks)
      post-infection also increased significantly (all P values < 0.01). During the
      first 3 weeks post-infection, the proportions of Tc1 cells increased most quickly
      than Tc2 cells did and Tc1 cells did at the other stages post-infection. However,
      the proportion of Tc2 cells increased most quickly 5 weeks post-infection than
      both Tc1 cells did and Tc2 cells did at the other stages post-infection. A
      positive correlation was found between the increases of the proportions of Thl
      cells and Tc1 cells ( r = 0.978, P = 0.004), and a positive correlation was also
      found between the increases of the proportions of Th2 cells and Tc2 cells ( r =
      0.974, P = 0.005). The SWA stimulation of splenocytes of mice in vitro
      significantly increased the proportion of Tc1 cells (P < 0.01) while the SEA
      stimulation of splenocytes of mice in vitro significantly increased the
      proportion of Tc2 cells ( P < 0.01). CONCLUSIONS: The proportions of Tc1 cells
      and Tc2 cells in T cells are significantly increased at different stages after S.
      japonicum infection. Tc1 cells are increased most quickly 3 weeks post-infection,
      and Tc2 cells are increased most quickly 5 weeks post-infection. A positive
      correlation is found between the proportions of Th cells and Tc cells in CD3+ T
      cells. SWA preferentially induces the increase of Tc1 cells in CD3+ T cells while
      SEA preferentially induces the increase of Tc2 cells in CD3+ T cells in vitro.

PMID- 22590861
TI  - [Studies on standardization of methods for screening molluscicides in laboratory
      IV sensitivity of Oncomelania snails from different months to niclosamide].
AB  - OBJECTIVE: To understand the sensitivity of Oncomelania snails collected from
      different months to niclosamide, so as to provide the scientific evidence for the
      standardization of methods for molluscicide screening and efficacy evaluation in
      laboratory. METHODS: The snails collected from the marshland of Zhenjiang City,
      Jiangsu Province month by month from June 2010 to May 2011. After being raised in
      laboratory for 24 h, the snails were randomly grouped, and then immersed in
      different concentrations of 50% wettable powder formulation of niclosamide
      ethanolamine salt at (25 +/- 1) degrees C with a humidity of 60%. The dead snails
      were identified and counted, and the mortality rate of snails and median lethal
      concentration (LC50) were calculated. RESULTS: When the snails were immersed in
      the solutions of niclosamide at concentrations of more than 0.5 mg/L for 24 h,
      all the snails collected from different months were dead, while 60%-100% of the
      snail mortality was achieved for 0.250 mg/L niclosamide, 3%-27% for 0.125 mg/L
      niclosamide, and 3%-20% for 0.062 5 mg/L niclosamide. When the concentration was
      lower than 0.032 mg/L, the niclosamide was not toxic to the snails within 24 h.
      The LC50 value was 0.140-0.209 mg/L for 24 h. When the snails were immersed in
      the solutions of niclosamide at concentrations of more than 0.5 mg/L for 48 h,
      all the snails collected from different months were dead, while 90%-100% of the
      snail mortality was achieved for 0.250 mg/L niclosamide, 3%-57% for 0.125 mg/L
      niclosamide, 3%-13% for 0.062 5 mg/L niclosamide, and 0-10% for 0.032 mg/L
      niclosamide. When the concentration was lower than 0.016 mg/L, the niclosamide
      was not toxic to the snails within 48 h. The LC50 value was 0.112-0.170 mg/L for
      48 h. There were no significant differences in the mortality of snails caused by
      niclosamide treatment observed at 24 and 48 h (P values = 0.374 and 0.267,
      respectively). CONCLUSIONS: There are little changes in the sensitivity of snails
      collected from different months to niclosamide, with minor fluctuations in LC50
      values. Such a finding indicates that the snails collected from different months
      have few effects on screening of molluscicides and efficacy evaluation.

PMID- 22590863
TI  - [Epitope identification of monoclonal antibody 5C6 against 14-3-3 protein of
      Schistosoma japonicum].
AB  - OBJECTIVE: To identify the epitope of monoclonal antibody (McAb) 5C6 against 14-3
      3 protein of Schistosoma japonicum by phage display peptide library. METHODS: The
      phage display 12-peptide library was screened with purified McAb 5C6 against 14-3
      3 protein of S. japonicum three rounds of bio-panning "adsorption-elution
      amplification" to enrich the specific binding phages. The single phage clones
      selected randomly were amplified, their genomic DNA were extracted and sequenced.
      The immune response characterization of phages with the same or high homologous
      foreign inserted DNA sequence was identified by ELISA and Western blotting for
      further defining the epitope recognized by McAb 5C6. RESULTS: A total of 33
      single phage clones were selected and sequenced. Among them, 25 shared the same
      foreign inserted DNA sequence of 5'-CCACCTAGTAGCAGACCGATTCTCAGTCGAAGGAAA-3',
      encoding a deduced peptide PPSSRPILSRRK. This peptide was not homologue to Sj14-3
      3 protein or any other known native protein in the world. The results of Western
      blotting showed that this peptide could be recognized by the sera of patients
      with schistosomiasis, but not by those of healthy persons. CONCLUSION: The mimic
      antigen epitope of McAb 5C6 against 14-3-3 protein of S. japonicum, which is a
      conformational epitope, has been defined successfully in this study.

PMID- 22590864
TI  - [Skin inflammation responses induced by heat shock protein 70 derived from
      Schistosoma japonicum in BALB/c mice].
AB  - OBJECTIVE: To study the skin inflammation responses induced by heat shock protein
      70 (rSj648/hsp70) from Schistosoma japonicum in BALB/c mice. METHODS: BALB/c mice
      were injected with 20 microg of LPS in abdominal skin or 100 microg of
      rSj648/hsp70, meanwhile, the PBS-treated group was set as blank. On days 1, 2, 4,
      7 after the immunization, dynamic changes of inflammation were observed by
      staining with HE; and the IFN-gamma mRNA expression was detected by real-time
      PCR. Results On day 1, the inflammation of the skins derived from mice injected
      with LPS was obviously, and then fell off gradually after day 1. Compared with
      the LPS-treated group, the inflammation responses induced by Sj648/hsp70 were
      longer and more intensive until until day 7. CONCLUSIONS: Heat shock protein 70
      (rSj648/hsp70) induces high protection against schistosome-infection contributing
      to predominant Th1 reaction and the correlation with high expression of IFN
      gamma.

PMID- 22590865
TI  - [Cross-section study on co-infection of HIV and Cryptosporidium].
AB  - OBJECTIVE: To investigate the co-infection status of HIV and Cryptosporidium, and
      explore the influencing factors associated with the co-infection. METHODS: A
      total of 309 people with HIV positive in Fuyang City of Anhui Province were
      recruited and their fecal and blood samples were collected for examinations of
      Cryptosporidium spp. infection and the levels of hemoglobin, cytokines and
      CD4+/CD8+ T-lymphocytes. Meanwhile, the questionnaire survey was conducted.
      RESULTS: Among 302 people involved in fecal examinations, the infection rate of
      Cryptosporidium spp. was 8.28%, and the difference between infection rates of the
      male (13.49%) and the female (2.92%) was statistically significant (P < 0.05).
      The multivariate logistic regression model showed that 4 factors were
      significantly associated with the coinfection of HIV and Cryptosporidium spp,
      including male (OR = 6.700, 95% CI: 2.030, 22.114), younger than 42 years old (OR
      = 4.148, 95% CI: 1.348, 12.761), level of IL-2 below 77 pg/ml (OR = 0.226, 95%CI:
      0.076, 0.674) and personal hygiene habits (OR = 0.324, 95% CI: 0.105, 0.994).
      CONCLUSION: The co-infection rate of Cryptosporidium spp. and HIV is high, the
      key targets of control are the people who are male, younger than 42 years old,
      with high level of IL2 and poor personal hygiene habits.

PMID- 22590866
TI  - [Expression of Toll-like receptor 4 in brain tissue of chronic Toxoplasma gondii
      infection rats and its effect on brain injury].
AB  - OBJECTIVE: To explore the expression of Toll-like receptor 4 (TLR4) in brain
      tissue of chronic Toxoplasma infection rats and its effect on brain injury.
      METHODS: Ten male SD rats were randomly divided into 2 groups, namely control and
      infection groups. Each rat in the infection group was intraperitoneal injected
      with Toxoplasma gondii tachyzoites 10(7)/ml x 2 ml, and that in the control group
      was injected with 2 ml sterile normal sodium. After 10 weeks, the expression of
      TLR4 mRNA in the brain was determined by RT-PCR, and the levels of IL-1beta and
      IL-4 in peripheral blood sera were detected by ELISA. RESULTS: Compared with the
      control group, the expression of TLR4 gene and the peripheral blood serum level
      of IL-1beta of rats in the Toxoplasma gondii infection group were both
      significantly increased, with all P values were less than 0.05, and the level of
      IL-4 was also increased, but the difference had no statistically significance (P
      > 0.05). CONCLUSION: TLR4 might be involved in inflammatory reactions of brain
      injury for chronic Toxoplasma gondii infection rats.

PMID- 22590867
TI  - [Construction of expression vector of ALAg and immune protection of its
      recombinant protein induced in mice].
AB  - OBJECTIVE: To determine the candidate genes for engineering vaccine of Ascaris
      lumbricoides. METHODS: pMD18-T-ALAg and plasmid expression vector pET-28a(+) were
      digested with BamH I and EcoR I and linked to each other. The resultant plasmid
      pET-28a(+)-ALAg was transferred into E. coli BL21 (DE3) and its expression was
      induced with IPTG, and the recombinant ALAg(rALAg) was purified. A total of 30
      mice were equally divided into 3 groups, the mice in each group were injected
      with rALAg-FCA, FCA and PBS respectively, then they were attacked by infectious
      eggs of Ascaris (3 600 per mouse). The IgG levels in sera of mice in each group
      were detected by indirect ELASA. RESULTS: rALAg was recognized by the sera from
      repeatedly Ascaris lumbricoides inoculated rabbits. The numbers of larvae of
      Ascaris lumbricoides from liver and lung of mice were 25.30 +/- 4.55 in the rALAg
      FCA group and 57.60 +/- 5.76 in the PBS group, respectively, the former being the
      reducing rate of 69.26%, and the difference among the 3 groups showed statistical
      significances (P < 0.01). The IgG levels (A450 value) of the rALAg-FCA, FCA and
      PBS groups were 0.858 +/- 0.003, 0.149 +/- 0.004 and 0.134 +/- 0.004,
      respectively, there were statistical differences among them (P < 0.01).
      CONCLUSION: ALAg can be used as a candidate gene of genetic engineering vaccine
      of Ascaris lumbricoides.

PMID- 22590868
TI  - [Improvement of fully automatically microscopic scanning system based on the oil
      lens and its application in reading of malaria blood smears].
AB  - OBJECTIVE: To improve the automatically microscopic scanning system based on the
      oil-lens and apply it in reading of malaria blood smears. METHODS: The software
      of the system was modified and optimized. A total of 115 blood films from
      Tengchong City of Yunnan Province were examined by the automatically systematic
      method or read by blood smear examination staff of Tengchong City and the
      accuracy, sensitivity and specificity were determined and compared between the
      two methods. RESULTS: The scanning of the system was speedier and the actual
      operation was more simple and convenient. The accuracy, sensitivity and
      specificity of the system were better than those of the professional staff. There
      was a significant difference of accuracy between the two methods (P = 0.002) and
      there was a significant difference of comprehensive sensitivity and specificity
      between the two methods (P < 0.01). Moreover, the system had the function of
      automatically saving scanning pictures which could be read again by everyone
      through the Internet. CONCLUSIONS: The fully automatically microscopic scanning
      system based on the oil-lens has many functions and the operation is simple. It
      can improve the speed, accuracy, sensitivity and specificity of malaria blood
      smears and those indices are much better than those of the reading smears under a
      microscope by the professional staff. Therefore, it is easier to be applied at
      the grassroots level.

PMID- 22590869
TI  - [Study on spatial distribution of advanced schistosomiasis at village level in
      Anxiang County based on geographic information system].
AB  - OBJECTIVE: To explore the spatial distribution and pattern of advanced
      schistosomiasis in Anxiang County so as to provide the evidence for improving
      advanced schistosomiasis control. METHODS: Based on the geographic database of
      advanced schistosomiasis distribution at the village level in Anxiang County,
      Hunan Province, the spatial autocorrelation analysis and spatial scan statistics
      were applied to analyze the spatial characteristics of distribution of advanced
      schistosomiasis. RESULTS: The global Moran's I of prevalence rate of advanced
      schistosomiasis was 0.06 (P > 0.05) and there was no spatial auto-correlation as
      a whole. The local spatial auto-correlation analysis showed that there were 9
      villages with statistically significant LISA value (P < 0.05), among which
      existed high-high, low-high and high-low types of auto-correlation model. The
      results of SaTScan statistics was the same as local spatial auto-correlation
      analysis and showed the existence of one cluster area. CONCLUSIONS: There are
      local spatial auto-correlation and spatial aggregation of advanced
      schistosomiasis in Anxiang County. According to the distribution characteristics,
      we can assign resource more reasonably and control schistosomiasis more
      effectively.

PMID- 22590870
TI  - [Questionnaire survey on replacing bovine with machine in Yangxin County].
AB  - A total of 405 households keeping cattle were surveyed by questionnaire in
      Yangxin County in 2008, the results showed that 215 of them (53.09%) were willing
      to replace cattle, 288 of them (71.11%) preferred to economic compensation, and
      117 of them asked for compensation with machine.

PMID- 22590871
TI  - [Effect of ecological civilized homestead construction on schistosomiasis
      control].
AB  - OBJECTIVE: To evaluate the effect of Ecological Civilized Homestead Construction
      on schistosomiasis control. METHODS: The data of ecological civilized homestead
      construction and schistosomiasis control were collected and analyzed in Meiwan
      Village, Shuangqiao Town, Danling County, Sichuan Province from 2004 to 2010.
      RESULTS: Ecological Civilized Homestead Construction was carried out from 2004 to
      2010. Totally 454 bio-gas pools were built. All the farmers used well water. The
      popularized rates of the household bio-gas pool, sanitary toilet, sewage
      treatment pool reached 100%. The number of cattle was 4, which decreased by
      91.30% compared with that in 2004, and all the cattle were fed in captivity. The
      schistosome infection rates of populations were 0.26% and 0.30% in 2005 and 2008,
      respectively, and nobody was infected in other years. The infection rate of
      cattle was 0 from 2004 to 2010. The awareness rate of knowledge about
      schistosomiasis control achieved 100% in the population over 6 years old. Most of
      the farmers could use certain protective measures while they were farming.
      CONCLUSION: The effect of ecological civilized homestead construction on
      schistosomiasis control is remarkable.

PMID- 22590873
TI  - [Investigation on prevalence of Spirometra mansoni sparganum infection in frogs
      from Henan Province].
AB  - OBJECTIVE: To understand the prevalence of Spirometra mansoni sparganum infection
      in frogs from Henan Province and analyze the risk of people suffering from
      sparganum infection. METHODS: The spargana were examined in the muscle of frogs
      collected from 12 sites of 5 regions in Henan Province, and the amount of
      spargana and their location were recorded. RESULTS: The natural infection rate of
      Spirometra mansoni spargana in frogs was 26.63% (306/1 149). There were totally 1
      897 spargana found in those frogs, and the average was 6.2 per frog. The
      infection rate of pond frogs was higher than that of toad, the difference was
      statically significant (chi2 = 30.42, P < 0.01). The natural infection rate of
      pond frogs in the nearby patients' residence was higher than that of pond frogs
      collected from the other sites, and the natural infection rate of frogs was lower
      in the west region of Henan than that in the other areas. The muscles of hind
      legs of the frogs was the most common parasitic location compared with other
      parts of the frogs, and the ratio was 73.74% (1 365/1 851). CONCLUSION: The frogs
      living in the nature are widely infected with Spirometra mansoni spargana in
      Henan Province, and the comprehensive measures should be taken for the prevention
      and control of sparganosis mansoni.

PMID- 22590872
TI  - [Effect of modified crushing-cercariae escaping method on detection of infected
      Oncomelania snails in field].
AB  - OBJECTIVE: To evaluate the effect of a modified crushing-cercariae escaping
      method on the detection of infected Oncomelania snails in the field. METHODS: A
      snail survey was carried out in Jingzhou City in the spring of 2011, and the
      villages were randomly divided into several groups, the coincidence rates,
      detection rates and the labour cost of the modified crushing-cercariae escaping
      method and crushing method were compared. RESULTS: A total of 14 snail spots were
      surveyed, and the coincidence rate of the two methods was 100%. In the spring
      snail survey, 539 villages and 3 536 spots with snails were detected by the
      modified crushing-cercariae escaping method, and 671 villages and 11 375 spots
      with snails were detected by the crushing method. The detection rates of villages
      with infected snails of the two methods were 25.79% and 28.46%, respectively, the
      difference between them was not statistically significant (chi2 = 1.079 5, P >
      0.05); and those of spots with infected snails were 5.57% and 3.66%,
      respectively, which had no significant difference between them (chi2 = 95.464 1,
      P < 0.01). Compared with the crushing method, the modified crushing-cercariae
      escaping method reduced labour cost by 87.86%, and saved 12.95 person-days per
      township. CONCLUSION: The modified crushing-cercaria escaping method can identify
      the spots with infected snails quickly and accurately with less labour cost,
      therefore, it is suitable for detecting environments with infected snails in
      batch in endemic areas.

PMID- 22590874
TI  - [Effect of intermittent irrigation in paddy fields on mosquito control].
AB  - OBJECTIVE: To investigate the effects of intermittent irrigation in paddy fields
      on mosquito control and the impact on growth and yield of rice. METHODS: The
      paddy fields were divided into an experimental group and a control group. In the
      same context of other measures, the experimental group was performed with
      intermittent irrigation and the control group with conventional irrigation. The
      densities of larvae of Anopheles sinensis and Culex tritaeniorhynchus were
      surveyed by the suction trapping method. The plant traits, leaf age process,
      tiller dynamics, yield structure and actual rice production were observed.
      RESULTS: Compared with the control group, the average densities of larvae of
      Anopheles sinensis and Culex tritaeniorhynchus were reduced of 10.32/m2 and
      13.93/m2 respectively in the experimental group, the control rates were 79.84%
      and 72.14% respectively, the average yield increased of 22.5 kg/667 m2, water
      conservation was 187.4 m3/667 m2, and the increased revenue was 75.78 yuan/667
      m2. CONCLUSIONS: The intermittent irrigation in paddy fields not only can control
      mosquito larva breeding effectively, but also save water and electricity, and
      increase the harvest.

PMID- 22590875
TI  - [Causes of death of advanced schistosomiasis patients in Jiaxing City from 1998
      to 2008].
AB  - OBJECTIVE: To understand the causes of death of advanced schistosomiasis patients
      in Jiaxing City from 1998 to 2008, so as to provide the evidence for improving
      the diagnosis and treatment of advanced schistosomiasis patients. METHODS: The
      data of advance schistosomiasis inpatients from April 1998 to March 2008 were
      collected, analyzed and combined with the following up to understand the epidemic
      characteristics and the causes of death of advance schistosomiasis patients.
      RESULTS: There were 2 004 of advanced schistosomiasis inpatients and 202 patients
      died. Among the 202 cases, 39.60% of patients were 60-70 years old and 34.65% 70
      80 years old. The death causes included upper gastrointestinal hemorrhage (69
      cases, 34.16%), hepatic encephalopathy (45 cases, 22.84%), and others.
      CONCLUSION: The upper gastrointestinal hemorrhage and hepatic encephalopathy were
      the main causes of death of advanced schistosomiasis patients in Jiaxing City
      during the past 10 years.

PMID- 22590876
TI  - [Ecological civilization and schistosomiasis control in Yujiang County].
AB  - This article describes the main approach of ecological civilization construction
      and great changes and achievements in the original schistosomiasis endemic areas,
      Yujiang County, Jiangxi Province. Ecological civilization is an important part of
      schistosomiasis control work.

PMID- 22590877
TI  - [Evaluation of molluscicidal effects of contracted responsibility system in
      Changshan County].
AB  - OBJECTIVE: To explore a new molluscicidal pattern suitable for the complicated
      environments in hilly regions, so as to provide the evidence for making the
      strategy of Oncomelania snail control. METHODS: The contracted responsibility
      system for snail control was implemented by government. The quality of control
      work was evaluated in the same year and the recent molluscicidal effect was
      assessed in the next spring. RESULTS: After the intervention, the decline rate of
      snail areas increased from 53.4% to 100%; the compression rate of snail spots
      increased from 54.6% to 100%; the input of fund for snail control decreased from
      2.03 Yuan/m2 to 0.69 Yuan/m2; the cost of snail control decreased from 3.73
      Yuan/m2 to 0.75 Yuan/m2; the work efficiency increased from 12.0 m2/(man x day)
      to 36.7 m2/(man x day); the molluscicide decreased from 7.50 tons/year to 3.20
      tons/year and the decline rate was 57.3%. The awareness rate and recognized rate
      of the contracted responsibility system for snail control were both 92.5%.
      CONCLUSION: The contracted responsibility system for snail control can increase
      financing efficiency, molluscicidal quality and work efficiency, and save
      molluscicide in complicated environments of hilly regions.

PMID- 22590878
TI  - [Influencing factors of distribution of Trichinella larvae in host muscles].
AB  - The distribution states of Trichinella spiralis larvae in host muscles are very
      complicated, and they are possibly influenced by many factors, such as host
      species, the physiological condition of host muscles, Trichinella species, the
      encapsulating condition of Trichinella spiralis encapsulated larvae, the level of
      infection and others. This paper summarizes the advance in the study of the
      influencing factors of distribution of Trichinella spiralis encapsulated larvae
      in host muscles.

PMID- 22590879
TI  - [Research and application of epitope].
AB  - Epitope is the basic functional motif of antigen inducing immune response. In
      immunological research and medical practice, the identification and selection of
      epitopes are the key points. This paper reviews the current progress of the
      epitope research and its application in disease diagnosis, vaccine research,
      disease treatment and other fields.

PMID- 22590880
TI  - [Endemic situation of schistosomiasis in Zongyang County from 2006 to 2010].
AB  - The analysis of endemic situation of schistosomiasis in Zongyang County from 2006
      to 2010 showed that the infection rates of schistosomiasis remained at a lower
      level with a declined trend. There were only distributed acute schistosomiasis
      patients each year. However, the densities of Oncomelania snails and infected
      snails still maintained at a high level. Therefore, we should continually
      strengthen the prevention efforts, especially infectious source control.

PMID- 22590881
TI  - [Environmental distribution and disposal measures of infected Oncomelania snails
      in Jingzhou City].
AB  - A survey of Oncomelania snail distribution was carried out with the systematic
      sampling method in combination with the environmental sampling method. A
      questionnaire survey was performed to find out the sites where stool examination
      positive patients were infected. The results showed that there were 1 721
      infected snail spots in Jingzhou City. Most of infected snail spots (94.1%) were
      only 500 m far away from the nearest residential areas from 2004 to 2010. About
      97% of patients considered that the sites where they were infected with
      schistosome were only 400 meters far away from their residential areas. In
      conclusion, the survey with a questionnaire method in patients with positive
      stool examinations can quickly identify the environments with infected snails.

PMID- 22590882
TI  - [Endemic situation of schistosomiasis in Donggou Village, a surveillance site, in
      Huarong County from 2005 to 2010].
AB  - From 2005 to 2010, the infection rates of schistosomiasis among residents (above
      6 years old) were 13.34%, 9.59%, 4.81%, 3.03%, 2.35% and 2.19%, respectively. The
      positive rates of schistosomiasis among domestic animals fluctuated from 2.50% to
      25.92%. Oncomelania snails were not found inside embankment since 1980, yet a
      high density of infected snails was found at low and uneven areas outside
      embankment. The cattle were the main infectious source and we should strengthen
      the administration and control of cattle.

PMID- 22590883
TI  - [Comparison of knowledge, attitude and practice of students left at home or not
      on schistosomiasis prevention and control].
AB  - The questionnaire survey on knowledge, attitude and practice (KAP)of students
      left at home or not about schistosomiasis prevention and control showed that
      there were no statistically significant differences of the scores of KAP between
      the two groups of students (all P values were above 0.05).

PMID- 22590884
TI  - [Epidemiological characteristics of soil-borne nematodiasis in Xiamen City].
AB  - The infection rate of soil-borne nematodes was 6.37% in Xiamen City, 2008, and
      among which the infection rates of hookworm, Ascaris lumbricoides, Trichuris
      trichiura and pinworm were 5.97%, 0.29%, 0.09% and 20.13%, respectively. The
      infection rate of soil-borne nematodes outside the island and that of pinworm in
      children were still high.

PMID- 22590885
TI  - [Comprehensive evaluation of blood smears of Plasmodium by osculating value
      method].
AB  - Based on the single indicator evaluation on making, dying and cleanness of blood
      smears of Plasmodium, the osculating value method was used to evaluate the blood
      smears from 16 microscopy stations in 8 towns of Lianyungang City
      comprehensively. The results showed that the blood smears were of high quality.
      The osculating value method is simple, reasonable, and applicable.

PMID- 22590886
TI  - [Effect of community intervention model of clonorchiasis in Zhaoyuan County].
AB  - After the community interventions of clonorchiasis control in Zhaoyuan County,
      the infection rate of Clonorchis sinensis of residents decreased from 67.43% to
      7.12%, and the awareness rates of healthy knowledge and healthy behavior
      increased by 124.55% and 156.03%, respectively. The control effect is
      significant.

PMID- 22590887
TI  - [Surveillance of schistosomiasis in Yanjiang Village, Hanjiang District, 2005
      2010].
AB  - The endemic situation of schistosomiasis and Oncomelania snail status in Yanjiang
      Village, Hanjiang District decreased significantly from 2005 to 2010. However,
      the surveillance in key population such as fishmen and boatmen still needs to be
      strengthened.

PMID- 22590888
TI  - [Effects of integrated malaria control measures in Shandong Province, 2010].
AB  - A total of 117 malaria patients were reported in Shandong Province, 2010 and the
      annual incidence was 0.13 per hundred thousand. Totally 23 cases of malaria were
      reported in Shanxian County, which was the most; and 6 patients who came back
      from Africa were reported in Daiyue County, which was the second. A total of 296
      230 fever patients were examined with blood tests, and the positive rate was
      0.03%. Totally 101 diapause patients were administered with medicine, and the
      administered rate was 95.28% and the regular administered rate was 100%. For the
      present patients, the regular administered rate was 100%. There were 73 malaria
      epidemic foci and they were all treated, and the area of residual spraying was
      51.98 hm2. The malaria epidemic was steady declined in Shandong Province.
      Although the prevention and control work achieved desired results, the monitor
      for mobile population and mosquitoes still should be strengthened to prevent the
      malaria epidemic increasing or outbreak.

PMID- 22590889
TI  - [Discussion of schistosomiasis infection source control].
AB  - At present, the strategy of schistosomiasis control is comprehensive control
      based on infectious source control. This paper discusses the comprehensive
      control measures, and suggests that we should strengthen the investigation of
      infectious sources and strengthen the control of infected Oncomelania snails.

PMID- 22590890
TI  - The importance for the MDG4 and MDG5 of addressing reproductive health issues
      during the second decade of life: review and analysis from times series data of
      51 African countries.
AB  - Addressing adolescent sexual and reproductive health issues are central to
      efforts for reducing childhood and maternal mortality embedded in MDG4 and MDG5.
      This paper reviews these issues in Africa and uses statistical methods for
      measuring changes to analyze recent and comparable time series data from 51
      African countries. The contribution of adolescent fertility to total fertility
      and mortality remains quite high. Delayed marriage is occurring concomitantly
      with postponement of sexual debut among unmarried adolescents. Six African
      countries are likely to achieve the MGD4 and five are likely to reach the target
      for the MDG5; the majority of sub-Saharan African countries will fall short of
      achieving these goals, not even by 2100 for many at current rates of change in
      progress indicators. Implementing ground-breaking nationally owned mortality
      reduction schemes covering preconceptional and interconceptional periods and well
      functioning comprehensive health-care system secured by sustained commitments and
      financial investments in health and social services are urgently needed, in order
      to repeal trends of further undoing successes achieved so far or slowing recent
      progress, thus hastening the pace of child and maternal mortality decline.

PMID- 22590891
TI  - Falling fertility and increase in use of contraception in Zimbabwe.
AB  - Zimbabwe does not feature much on the current debate of fertility transition in
      sub-Saharan Africa. This article is trying to fill this gap by analysing the ZDHS
      data. The total fertility rate of Zimbabwe was close to 7 births during
      independence in 1980. However, it has declined to 3.8 in 2006. This does not only
      show that fertility in Zimbabwe has been declining over the years, but it is one
      of the lowest in the region. The fertility trend observed is mainly explained by
      use of contraception. The contraceptive prevalence rate was 60 percent in 2006.
      It is noted that the contraceptive uptake has continued to increase even during
      the years when Zimbabwe was going through serious political, economic, social and
      health challenges. This is because the groundwork done on the family planning
      programme soon after independence put a solid foundation in motivating women to
      use contraception.

PMID- 22590892
TI  - Trends in contraceptive use among female adolescents in Ghana.
AB  - Within the past one and half decades many efforts have been made to improve the
      availability and access to adolescent sexual and reproductive health services.
      Despite these efforts, adolescents still face a number of sexual and reproductive
      health problems. This paper uses data from the 2003 and 2008 Ghana Demographic
      and Health Surveys to examine changes in contraceptive use among sexually active
      female adolescents (15-19 years old). The results show that between 2003 and 2008
      there was a significant increase in the current use of any contraceptive method
      (from 23.7% to 35.1%, p = 0.03). It also indicates a shift from modern to
      traditional contraceptive methods. Traditional methods recorded about 60% (7.8
      percentage points) increase as compared to 5.5% (2.6 percentage points) for
      modern methods. Also ever use of any traditional method recorded a higher
      increase as compared to any modem method. There was a slight decline 7% (4.4
      parentage points) in the number of non-users who intended to use contraceptives
      in the future. On the whole the findings indicate increasing unmet need for
      modern contraception due to barriers such as limited access, cost and
      misconceptions about the effects of contraceptives.

PMID- 22590893
TI  - Social determinants of reproductive health in Morocco.
AB  - Moroccan population has known a growing demographic trend. However, beyond the
      global tendency, reproductive health remains characterised by inequalities and
      disparities between urban and rural, rich and poor, developed and deprived
      regions. In this study, we relied mainly on data and statistics provided by the
      last five censuses, the four Demographic Health Surveys, Multiple Indicator
      Cluster Surveys, reports of international bodies and publications dealing mainly
      with health and development in the Arab World. During the last decades, fertility
      declined due to different parameters. Infant mortality decreased and should reach
      the corresponding Millennium Development Goal whereas maternal mortality has
      stayed nearly constant. The achievements accomplished in reproductive health
      remain insufficient. Family planning and contraception policies need to reach
      more women; and antenatal and postnatal care should be enhanced especially
      towards poor women living in rural areas and deprived regions.

PMID- 22590894
TI  - Qualitative study of reasons for discontinuation of injectable contraceptives
      among users and salient reference groups in Kenya.
AB  - Discontinuation of contraception is a major problem in Kenya. Even though they
      want to space or limit their births, over a quarter of contraceptive injectable
      users discontinue use of the method within 12 months of beginning use. Fourteen
      focus group discussions were conducted in Nyando District, Kenya among current
      contraceptive injectable users and their salient reference groups (e.g. husbands,
      mothers-in-law, community leaders, service providers) to understand why women
      discontinue using contraceptives (with a focus on injectables). Thematic analysis
      was performed using NVivo 8 software. Discontinuation of contraceptives in Nyando
      District occurs for logistical, social and medical reasons. Common reasons for
      discontinuation include side effects, husbands' opposition, provider and/or
      clinic restrictions, misconceptions about injectables, stock outs, and lack of
      cash to pay for family planning services. This research expands the literature by
      examining social influences on discontinuation by incorporating the perspectives
      of salient reference groups. The results suggest points of intervention for
      increasing continuation in this community and similar resource-poor settings.

PMID- 22590895
TI  - Sex of preceding child and birth spacing among Nigerian ethnic groups.
AB  - In seeking for more effective ways of fertility control and improvement of
      maternal and child health through birth spacing in a predominantly patrilineal
      society like Nigeria, this study explores how the sex of a previous child affects
      birth interval among ethnic groups, controlling for demographic and socioeconomic
      variables. The study utilized birth history data from the 2008 Nigeria
      Demographic and Health Survey. The findings showed that the effect of sex of
      prior births on the birth interval is slightly significant among the Igbo and the
      Southern minorities, who tend to desire to have a male child sooner if preceding
      births were female. Among all the ethnic groups, women who are yet to meet their
      ideal sex preference have a shorter birth interval than those who have. Apart
      from the evident sex preferences, these results suggest that Nigerian parents
      also undertake sex balancing among their children. There is a consistent and
      strong relationship between the survival of a child and subsequent birth
      interval, which suggest that women have a short birth interval, and hence a large
      family size, because they are not certain that their children would survive.

PMID- 22590896
TI  - Pregnant women's beliefs, expectations and experiences of antenatal ultrasound in
      Northern Tanzania.
AB  - This qualitative study explored pregnant women's beliefs, expectations and
      experiences of the recently introduced antenatal ultrasound service in
      BomaNg'ombe hospital, Tanzania. Thematic analysis of 25 semi-structured
      interviews and 41 questionnaires was employed. The majority of women desired
      ultrasonography despite many not understanding the procedure or purpose.
      Patient's expectations included discovering fetal position, fetal sex and
      pregnancy problems. However, women frequently over-estimated the capacity of
      ultrasound, and had significant fears of harm. One sixth of questionnaire
      respondents said they did not want ultrasonography. Nonetheless since the service
      was introduced no woman has declined, and numerous interviewees believed scans
      were obligatory. Despite fears, some women reported enjoyment of ultrasound.
      Interviewees believed ultrasound would increase antenatal care (ANC) attendance.
      An informed consent policy and an education campaign are needed to reduce fears
      and maximise uptake and health gains. The effects of ultrasound availability on
      timely ANC uptake, including amongst women not currently accessing ANC, should be
      further researched.

PMID- 22590897
TI  - Unintended pregnancy and termination of studies among students in Anambra state,
      Nigeria: are secondary schools playing their part?
AB  - This study evaluated efforts of secondary schools to prevent unintended pregnancy
      among students and their reactions to pregnant students before and after
      delivery. A cross-sectional survey of 46 teachers in three public and two private
      schools in Anambra state, Nigeria was carried out. Information was collected
      using self-administered questionnaire. Of all the teachers in the study, 87%
      reported unintended pregnancies among students in the previous 3 years. Expulsion
      (43%) and suspension (28%) were the most common reactions. Private schools were
      more likely to expel pregnant students than public schools. Following the
      delivery of their babies, 43% discontinued their education in the same school,
      whereas 37% continued their education in a different school. Counselling was
      given before suspension or expulsion in 4% of public schools and 15% of private
      schools. Majority of the schools (61%) did not have sex education as part of
      their schools' curriculum. Students should be re-admitted in order to ensure
      continuity of their academic development, prevent unemployment and mitigate
      poverty-induced repeat pregnancy.

PMID- 22590898
TI  - User and provider perspectives on emergency obstetric care in a Tanzanian rural
      setting: a qualitative analysis of the three delays model in a field study.
AB  - The aim of this field study was to analyze the main dynamics and conflicts in
      attending and providing good quality delivery care in a local Tanzanian rural
      setting. The women and their relatives did not see the problems of pregnancy and
      birth in isolation but in relation to multiple other problems they were facing in
      the context of poverty. Local health professionals were aware of the poor quality
      of care at health facilities but were still blaming the community. The study
      describes the difficulties within the conceptual framework of the widely used
      "three delays model" to disentangle different perspectives and to identify a
      feasible strategy of action to improve access to timely and effective emergency
      obstetric care. There seems to be a need for a supplementary analytic model that
      more clearly has the health system as the central agent responsible for improving
      maternal health. A modified "actantial model is suggested for that purpose.

PMID- 22590899
TI  - Regional patterns and correlates of HIV voluntary counselling and testing among
      youths in Nigeria.
AB  - Prevalence of Voluntary Counselling and Testing (VCT) for HIV among young people
      in Nigeria is low with implications on the epidemic control. Using the 2003
      Nigerian National Demographic and Health Survey, we examined the regional
      prevalence, pattern and correlates of VCT for HIV among youths aged 15 to 24 in
      Nigeria. Analysis was based on 3573 (out of 11,050) observations using logistic
      regression model to estimate the effects of identified predictors of volunteering
      for HIV testing. Results show that national prevalence of VCT is low (2.6%) with
      regional variations. Generally, the critical factors associated with VCT uptake
      are age, sex, education, wealth index and risk perception with North (sex,
      education, religion, occupation and risk perception) and South (age and
      education) variance. It is recommended that Nigerian HIV programmers should
      introduce evidence based youth programmes to increase the uptake of VCT with
      differing approaches across the regions.

PMID- 22590900
TI  - Knowledge and practices of emergency contraception among Ghanaian women.
AB  - The use of emergency contraceptives (EC) to prevent unwanted pregnancies when
      effective contraception has not been used is universally acknowledged. A study
      looked at the knowledge and practices of emergency contraception in 476 women in
      the reproductive age in Ghana. Knowledge and usage of EC applied to 57% and 41%
      of participants, respectively. Knowledge was independent of age (p = 0.26),
      marital status (p = 0.14) and level of education (p = 0.21). Drugs (85.6%),
      herbal preparations (14.4%) and douching (43%) were used for emergency
      contraception. Drugs used included the combined Pill-24.0%, Postinor-28.5% and
      Norethisterone-43%. Only 44% correctly used drugs as EC. There is a high level of
      knowledge about EC as well as usage in the country. There is general misuse
      ofnorethisterone as EC. There is no knowledge in this study population that
      intrauterine device can be used as EC.

PMID- 22590901
TI  - Office microlaparoscopic intrafallopian transfer of day one zygote versus day
      three embryo transfer after previous failed ICSI trials.
AB  - The objective of the study was to investigate whether transferring zygotes on day
      1 would result in similar pregnancy rates compared to transferring cleavage stage
      embryos on day 3 in a prospective randomized trial, using the office
      microlaparoscopic procedure. Patients undergoing IVF/ICSI treatments were
      randomized to either day 1 or day 3 transfers after previous failed ICSI trials
      due to failed implantation. The primary outcome measure was pregnancy rate.
      Pregnancy rates were higher in day 3 group (55/131, 42%) when compared to day 1
      (34/123, 28%, P = 0.024). Similarly, implantation rates were higher in day 3
      group (P = 0.03). There were more cycles with cryopreservation in the day 1 group
      (P < 0.001). Embryo quality on day 3 was similar between pattern 0 and non
      pattern 0 zygotes. Day 3 embryo transfers result in better pregnancy and
      implantation rates compared to day 1 zygote transfers.

PMID- 22590902
TI  - Round ligament varicosities mimicking inguinal herniae in pregnancy--a diagnostic
      dilemma.
AB  - Round ligament varicosities are rare surgical entities which can occur during
      pregnancy and mimic inguinal herniae. Correct diagnosis by clinical examination
      and ultrasonography can avoid an unnecessary surgical operation during pregnancy
      and its related complications. We present one case of 26 years pregnant lady
      reporting with bilateral round ligament varicosities.

PMID- 22590903
TI  - Primary pelvic hydatid cyst an unusual cause of cystic adnexal image (mass).
AB  - Hydatid cyst is a parasitic human infection which is endemic in North Africa. It
      is more frequently localized in the liver and the lung. Involvement of others
      sites is usually secondary to these primary localizations. We report 2
      exceptional cases of primary pelvic hydatid cyst diagnosed respectively in a 37
      year-old and in a 48-year-old women. These cases will focus on the different
      characteristics of the infection, and the benefit of including epidemiologic
      arguments in using the diagnostical approach of adnexal masses.

PMID- 22590904
TI  - [Gap junctions in sea anemone, Nematostella vectensis, embryo].
AB  - Gap junctions (GJs) are composed of membrane proteins that form channels
      connecting the cytoplasm of adjacent cells and permeable to ions and small
      molecules. They are considered to be the main or only type of intercellular
      channels and a universal feature of all multicellular animals (Metazoa). Till
      recently, sea anemones and corals (Anthozoa, Cnidaria) appeared to be an
      exception from this rule. There were no structural or physiological data
      supporting the presence of GJ in Anthozoa. For some time no genes homologous to
      GJ proteins (connexins or pannexins) were detected in sea anemone Nematostella
      vectensis (Cnidaria, Anthozoa) or other Anthozoa genomes. Recently, pannexin
      homolog was found in Nematostella. Our intracellular recordings demonstrate
      electrical coupling between blastomeres in embryos at the 8-cells stage. At the
      same time, carboxyfluorescein fluorescent dye did not diffuse between
      electrically coupled cells, which excludes the possibility that the observed
      electrical coupling is mediated by incomplete cytoplasm separation during the
      cleavage. These data support the idea that GJ are ubiquitous for Metazoa, and
      pannexins are universal GJ proteins.

PMID- 22590905
TI  - [Ecological, functional, and thermodynamic prerequisites and consequences of
      homoeothermy origin and development, with avian energetics as a case study].
AB  - Homoeothermy has formed in birds and mammals independently and in different
      geological ages. However, in both groups it originated as a side effect of
      selection for aerobic metabolism improvement that provided a higher level of
      activity. Advantages of having high and stable body temperature, which are
      inevitably related with metabolism intensification, led to development of
      thermoregulatory adaptations such as fur and feathers. This made it possible to
      retain the metabolically generated heat and reduce heat absorption in hot
      environments. Emergence of homoeothermy with aerobic supply of motion activity,
      possibilities to regulate the level of metabolism and thermolysis, has opened a
      lot of opportunities for homoeothermic animals. Achieving such a level of energy
      utilization allowed them to maintain activity for a longer time, while its
      sensory support led to complication and diversification of birds' behavioral
      repertoire (as well as that of mammals) facilitating the conquest of almost
      entire part of the biosphere that is suitable for living. This process was
      favoured by the development of nurturing and passing on the information,
      collected throughout the life, to new generations. Formation of high levels of
      aerobic metabolism in birds and mammals was proceeding in parallel among
      different groups of reptilian ancestors. The level of homoeothermy, at which
      aerobic metabolism is able to maintain prolonged activity, developed in birds and
      mammals in different ways: they have got dissimilar partitioning of venous and
      arterial networks, erythrocytes with or without a cell nucleus, different lungs
      design--but, at that, similar minimum metabolic power and rather close body
      temperatures which correspond well to the environmental conditions on the Earth.
      Natural selection allowed animals with high energetic metabolism to increase
      their diversity and abundance, but only when homoeothermic animals could satisfy
      their demands for food resources, that have risen manifold. That happened in the
      middle of Cretaceous, in time with the appearance of angiosperms and expansion of
      related fauna of invertebrates.

PMID- 22590906
TI  - [Analysis of G.F. Gause experimental time-series by means of continuous-time
      models].
AB  - Four population dynamics models, namely Verhulst, Gompertz, Rosenzweig, and
      Svirezhev ones, have been used to approximate two well-known time-series of
      Paramecia aurelia and P. caudatum population size (Gause, 1934). The parameters
      are estimated for each of the models by the least-square method (with global
      fitting) in two different ways: with and without an additional upper bound for a
      parameter value. In the latter (traditional) case, when the deviations of
      theoretical (model) trajectories from experimental time-series have been tested
      for normality (Kolmogorov-Smirnov test, Shapiro-Wilk test) with zero average, and
      for the presence/absence of serial correlations (Durbin-Watson criteria), the
      best results are obtained for the Gompertz and Verhulst models. In the former,
      more realistic, case (when we impose an additional constraint that the parameter
      meaning the carrying capacity of the environment has to be greater than any
      element in the sample), the best results are observed for the Gompertz model.
      Under this constraint, the canonical technique for deviation analysis can be
      applied in a restricted version only.

PMID- 22590907
TI  - [Geographic variations in freshwater molluscs].
AB  - The phenomenon of geographic variation is known in practically all taxa of living
      beings. However, the reality of this phenomenon in freshwater molluscs (snails
      and bivalves) has many times been questioned in the past. It was accepted that
      these animals do not demonstrate spatially-oriented variation, where specific
      "local race" is arisen in each specific habitat. Till the beginning of 1970s,
      there was no statistical evidence that geographic clines in freshwater molluscs
      really exist. However, a few species of freshwater molluscs has been studied in
      this respect so far, therefore it is almost impossible to draw any general
      patterns of geographical variation in this group of animals. Most species of
      freshwater molluscs studied to the date exhibit statistically significant
      decrease of their body size in the south-north direction. Perhaps, it may be
      explained by decrease of the duration of the growth season in high latitudes.
      Some species of freshwater snails demonstrate clinal changes in shell
      proportions. This allows to reject subspecies separation within these species
      since diagnostic characters of such "subspecies" may blur when geographic
      variation is taken into consideration. The data on geographic variation in
      anatomical traits in freshwater molluscs is much more scarce. At least one
      species of pond snails (Lymnaea terebra) demonstrates clinal variation in
      proportions of the copulative apparatus in the south-north direction. Further
      studies of geographic variation in freshwater molluscs should reveal whether it
      is truly adaptive, i.e. whether geographical clines have underlying genetic
      basis. Otherwise, the clines may arise as a result of direct modifying effect of
      a habitat.

PMID- 22590908
TI  - [Decorative forms of hamsters Phodopus (Mammalia, Cricetinae): an analysis of
      genetic lines distribution and peculiarities of hair changes].
AB  - Three species of dwarf hamsters (genus Phodopus, family Cricetidae) inhabit some
      regions of Russia, Kazakhstan, Mongolia, and China, each having quite extensive
      range. In recent decades, the dwarf hamsters became widely spread all over the
      world, initially as laboratory animals and later as popular pets. By now, there
      is lot of decorative breed lines and colored forms of these animals. Comparison
      of mtDNA nucleotide sequences of dwarf hamsters acquired in pet shops of some
      countries in Europe, South-East Asia and North America with distribution of mtDNA
      haplotypes within natural ranges showed the limitation of decorative line
      founders' points of origin by one region for each of the species. All haplotypes
      found in decorative Dzungarian hamsters (Ph. sungorus) purchased ounside Russia
      coincide with or are significantly close to haplotypes spread in the southern
      part of West Siberia (Russia) and adjacent regions of Kazakhstan; haplotypes of
      decorative Campbell's hamster (Ph. campbelli) belong to haplogroup of this
      species natural populations inhabiting South Tyva (Russia); and all studied
      decorative Desert hamsters (Ph. roborovskii) had one hapotype specific for South
      Eastern Kazakhstan. The review of the history of researches on dwarf hamsters
      biology allows to determine delivery of hamsters from mentioned regions to
      scientific laboratories and zoos by certain expeditions and/or researchers.
      Unlike hamsters with natural hair color, the colored hamsters have no normal
      hair. Their hair is dull and straggly. The hair differentiation (presence of
      different hair types and their size characteristics) gets broken and results in
      deformation, bending, and splitting of the shaft, cracks in cuticle, change of
      configuration and location of medulla, uneven development of cortex. It is
      assumed that these destructive changes are associated with genetic
      characteristics of these hamsters' colored forms.

PMID- 22590909
TI  - [Review of: "Methodological approaches to ecological estimation of forest cover
      within a small river basin"].

PMID- 22590910
TI  - [The role of apoptosis in the etiopathogenesis of autoimmune thyroiditis].
AB  - Autoimmune thyroiditis (Hashimoto's disease) is a polygenic disorder with complex
      etiopathogenesis. Apoptosis is proposed as one of its mechanisms. Programmed cell
      death is essential for the maintenance of homeostasis, but when it is
      deregulated, it may contribute to the development of disorders. There are two
      apoptotic pathways: intrinsic and extrinsic. The extrinsic pathway maybe
      activated among others through FasL binding to its receptor Fas. The FasL induced
      apoptotic pathway proceeds with cascade activation of following caspases, with
      final effector proteins recruitment. There is also a group of inhibitory proteins
      of apoptosis, where the Bcl-2 protein predominates. In the course of Hashimoto's
      disease the following aberrations are encountered: increased Fas/FasL expression,
      caspases and Bid protein concentrations, decreased Bcl-2 concentration and at the
      same time increase of Bcl-2 within intrathyroidal lymphocytes. They favor the
      thyrocytes apoptosis and thyroid gland destruction. Synergistically acting
      proapoptotic cytokines IFN-gamma and TNF or IL-beta, are considered to be major
      factors of the abnormalities mentioned above. TSH, T3 and T4, TSAb and TSBAb
      antibodies and iodide concentration may also play a role in pro- and
      antiapoptotic factors expression regulation. The role of TRAIL protein in the
      course of Hashimoto's thyroiditis needs evaluation. The current data on the role
      of apoptosis in the etiopathogenesis of the autoimmune thyroiditis will be
      presented and discussed.

PMID- 22590911
TI  - [Resting heart rate in subjects with carbohydrate disorders].
AB  - Large epidemiological studies conducted during last 25 years confirmed the
      importance of resting heart rate as an independent risk factor for total and
      cardiovascular mortality in females and males, both in overall population and in
      subjects with cardiovascular diseases such as arterial hypertension, myocardial
      infarction, coronary heart disease, heart failure or left ventricular
      dysfunction. The aim of the study was to evaluate the resting heart rate (HR) in
      subjects with carbohydrate disorders. MATERIAL AND METHODS: The study comprised
      112 subjects with carbohydrate disorders (54 females and 58 males), aged 30-78
      (57.4 +/- 9.6) years. Carbohydrate disorders were diagnosed according to the
      Polish Diabetes Association criteria from 2007 (group I). 56 subjects had
      impaired fasting glucose (IFG), 36 - impaired glucose tolerance (IGT) and 20 -
      type 2 diabetes. Comparative group comprised 30 subjects without cardiovascular
      diseases and carbohydrate disorders (15 females and 15 males), aged 29-64 (52.7
      +/- 8.8) years (group II). The fasting serum glucose level was evaluated using an
      enzymatic method, Kone Pro biochemical analyzer and bioMerieux Glucose RTU kit.
      In subjects with fasting glucose level > or = 100 mg/dl, an oral glucose
      tolerance test (OGTT) was performed. Additionally, in all subjects resting heart
      rate (HR) was measured, after 10-minute rest, at a room temperature of about 20
      degrees C. The measurements were made threefold, every 5 minutes and mean value
      was assessed. RESULTS: In subjects with carbohydrate disorders HR was
      significantly higher than in comparative group (82.79 +/- 12.1 vs 69.9 +/-
      9.56/min; p < 0.05). In group of subjects with carbohydrate disorders in
      comparison to comparative group, resting heart rate < 60/min occurred in 1.79 vs
      13.33%, in intervals: 60-70/min in 14.29 vs 50%. 71-80/min in 33.93 vs 23.33%, 81
      90/min in 25% vs 13.33%, and above 90/min in 25% of studied group (p < 0.05). On
      the basis of ROC curve analysis and odds ratio (OR) it was shown that HR > or =
      72.5/min is an independent risk factor for carbohydrate disorders. CONCLUSIONS:
      Resting heart rate > or = 72.5/min is an independent risk factor for carbohydrate
      disorders and increases its risk more than ninefold.

PMID- 22590912
TI  - [Assess the impact of concentrations of inflammatory markers IL-6, CRP in the
      presence of albuminuria in patients with type 2 diabetes].
AB  - Diabetic nephropathy is one of the most common complications of diabetes. Symptom
      of nephropathy is albuminuria, in which the mechanism of formation may
      participates CRP and IL-6. The aim of the study was to evaluate the
      concentrations of CRP and IL-6 depending on the irregularity of metabolic
      patients with type 2 diabetes and their impact on the occurrence of albuminuria.
      MATERIAL AND METHODS: The study was conducted among 68 patients with type 2
      diabetes with albuminuria. Patients were divided into groups: group I - patients
      with type 2 diabetes with HbA1c > or = 6.1 - < or = 6.5%, group II - patients
      with type 2 diabetes with HbA1c > 6.5 - < or = 10.0%, K - control group, 21
      patients with essential hypertension with albuminuria. The material was consisted
      of venal extracted for clot drawn from the basilic vain. IL 6 concentration was
      assessed using the ELISA method. The percentage of hemoglobin A1c (HbA1c), CRP,
      the extent of albuminuria was determined by immunoturbidimetric method. RESULTS:
      The mean urinary albumin excretion was highest in the second study group, lowerin
      the test group, the lowest in the control group. The average concentration of IL
      6 and CRP was highest in group I, lower in group II, the lowest in the control
      group (p > 0.05). It has been shown a positive correlation between serum CRP and
      the magnitude of albuminuria in the test group of patients with type 2 diabetes
      with HbA1c > or = 6.1 - < or = 6.5% (p < 0.037). The relationship between serum
      CRP and the magnitude of albuminuria in the control group of patients with
      essential hypertension were at the border of statistical significance (p <
      0.057). Not shown a positive correlation between these parameters in the second
      group of patients with type 2 diabetes with HbA1c >6.5 - < or = 10.0%.
      CONCLUSIONS: In patients with type 2 diabetes with better metabolic control,
      protein CRP is a sensitive marker of albuminuria.

PMID- 22590913
TI  - [Helicobacter pylori infection in pancreatic cancer].
AB  - Despite some advances in the oncological managament, pancreatic cancer remains a
      clinical problem and has remained leading cause of cancer deaths. The association
      between Helicobacter pylori (H. pylori) infection and pancreatic was suggested,
      but the issue remains of contentious. The aim of the study was to determine the
      relationship between H. pylori infection and pancreatic cancer development on a
      sample of Polish population. MATERIAL AND METHODS: 139 patients with pancreatic
      cancer and 177 controls were included in the study. Seropositivity for H. pylori,
      including CagA protein were assessed by the enzyme-linked immunosorbent assay and
      Western blot, respectively. The frequency of H. pylori in pancreatic cancer
      patients and controls were compared adjusted for age, sex, cigarette smoking and
      a family history of cancer in the logistic regresion model. RESULTS: No
      significant differences between pancreatic cancer patients and controls were seen
      according to H. pylori seropositivity (87.1 vs 82.5%; OR = 1.27; CI95%: 0.64
      2.61; p = 0.514) and CagA seropositivity (83.5 vs 84.9%; OR = 0.90; CI95%: 0.46
      1.73; p = 0.744). CONCLUSIONS: The study didn't support previous observations of
      H. pylori infection as a plausible pathogenic risk factor for pancreatic cancer
      development. The high prevalence of infection in the control group may explain
      why the earlier reports of a positive association between H. pylori infection and
      pancreatic cancer could not be confirmed in the study.

PMID- 22590914
TI  - [Liver damage in the course of Langerhans cells histiocytosis--case report].
AB  - Langerhans cell histiocytosis is a disorder of unknown etiology characterized by
      proliferation of histiocytes originating from dendric cells. It usually affects
      children. LCH is claimed to be a difficult diagnostic challenge. We present a
      case of multi-organ LCH with severe liver damage. Initial symptoms of disease,
      the results of additional tests including histological assessment of liver
      suggested an autoimmune hepatitis. Histopathological evaluation of sequentially
      occurring lesions in the intestines and lungs made it possible to clarify the
      diagnosis. As there is no effective treatment--the progression of the disease
      resulted in patient being qualified for liver transplantation.

PMID- 22590915
TI  - [Systemic lupus erythematosus--still current clinical and diagnostic problem].
AB  - Systemic lupus erythematosus (SLE) is a common autoimmune disease of unknown
      etiology that frequently affects women of childbearing age. SLE is associated
      with impairments in immune system, which is a consequence of increased production
      of various autoantibodies. This disease is still a major diagnostic and
      therapeutic problem. Some hope to explain the complex etiopathogenesis of the
      disease creates a monitoring function of the immune system. A chance for patients
      are biologically targeted therapies that affect the critical stages of the
      disease and autoimmune inflammatory processes.

PMID- 22590916
TI  - [Multiple endocrine neoplasia type 1].
AB  - Multiple endocrine neoplasia (MEN) type 1 exhibits an autosomal dominant pattern
      of inheritance and results from mutation of the MEN-1 gene that is a tumor
      suppressor gene acting on the transcriptional level. The disease is characterized
      by a variety of neuroendocrine neoplasias and hormone excess syndromes. The major
      components of MEN-I are hyperparathyroidism due to multiple parathyroid adenomas,
      pancreatic or duodenal neuroendocrine tumors, and pituitary adenomas, in addition
      to some less common neoplastic manifestations. The development of the tumors
      often follows a substantially similar pattern: the initial lesion is a diffuse
      hyperplastic proliferation of the affected endocrine tissue with bilateral
      involvement of pair organs, followed by development of multiple micro- and,
      eventually, macronodular lesions. Its unpredictable course causes that there is
      controversy regarding treatment of the different manifestations and screening
      modalities of this disorder. This article reviews our current approach to the
      diagnosis, surveillance and management of these patients.

PMID- 22590917
TI  - [Current views on etiology, pathophysiology and clinical manifestations of
      acromegaly].
AB  - Acromegaly is a relatively rare disease caused by excess secretion of growth
      hormone, usually from a pituitary somatotrope adenoma. Most of the tumors causing
      acromegaly are sporadic but in some cases the disease results from the presence
      of an inherited endocrine syndrome including type 1 multiple endocrine neoplasia,
      McCune-Albright syndrome and Carney complex. Because of the slow evolution of
      signs and symptoms, acromegaly can be a diagnostic challenge. The disease is
      characterised by significantly increased morbidity and mortality, both of which
      are secondary to the involvement of multiple organ systems. This prompts the need
      for the rapid and accurate recognition and management of this disorder.
      Acromegaly is diagnosed on the basis of clinical picture, hormonal assays and
      radiologic imaging of the pituitary gland. This article reviews the etiology,
      histopathological picture, clinical features and current diagnostic strategies in
      acromegaly and prognosis in this disorder.

PMID- 22590918
TI  - [Molecular aspects of allergy to plant products. Part I. Class I and II allergens
      and crossreactivity of IgE antibodies].
AB  - Food allergies are adverse immunologic reactions that might be due to IgE--or
      none IgE-mediated immune mechanisms or mixed. One of the more common and
      typically most mild forms of IgE- mediated food allergy is the so-called oral
      allergy syndrome (OAS), although systemic symptoms after ingesting a particular
      fruit or vegetable can occur. Pollen food syndrome is the most common food
      allergy in adolescents and adults. It develops as a consequence of shared
      epitopes in the primary and tertiary structures of pollen and food allergens. The
      authors describe class I and class II allergens, as well as molecularly
      determined IgE-crossreactivity phenomenon. Also the problem of symptom-free
      consumed pollen-related food allergens, which might cause T cell-mediated late
      phase skin reactions in patients with pollen allergy and atopic dermatitis, is
      taken up.

PMID- 22590919
TI  - [Epidemiology and risk factors of the oral carcinoma].
AB  - Oral cancer is the eleventh most common malignancy in the world, with squamous
      cell carcinoma being a predominant histologic type. The highest incidence is
      observed in India, Australia, Brazil, France and South Africa. In Europe the most
      affected regions are France, French-language cantons of Switzerland, northern
      Italy and countries of the Middle-East Europe. In most regions cancer is much
      more common in man. Oral cancer accounts for 1.34% of all registered malignant
      tumors in Poland in 2008. Etiology of the oral squamous cell carcinoma is
      complex. The most important risk factors, especially in well-developed countries
      are tobacco smoking and alcohol exposure. Alcohol promotes cancer development not
      only administered as a stimulant but also as a component of mouthwashes. Betel
      chewing, human papilloma virus infection, deficiency of vitamin A, riboflavin and
      iron, poor mouth hygiene and immunosuppressive therapy are also associated with
      higher incidence of oral carcinoma. More recently, relation between individual
      increased susceptibility to oral cancer and some genes polymorphisms, especially
      those encoding cytokines and enzymes engaged in alcohol metabolism has been
      found.

PMID- 22590920
TI  - [Chemoprevention of oral cancer--clinical and experimental studies].
AB  - Chemoprevention is one of the cancer prevention methods, applied for the oral
      squamous cell carcinoma and its main precursor lesions--leukoplakia and
      erythroplakia. Presently, the most extensive clinically studied group used in
      such cases are retinoids: vitamin A (retinol), 13-cis-retinic acid
      (isotretinoin), N-(4-hydroxyphenyl)retinamide (fenretinide) and precursor of
      vitamin A--beta-carotene. However, despite good short-time effectiveness,
      retinoids do not prevent recurrences of the lesions and insignificantly increase
      cancer-free survival. Moreover, they are also characterized by relatively high
      toxicity. Vitamin E, Bowman-Birkprotease inhibitor, Spirulina fusiformis and
      green tee extracts as well as traditional Chinese herbs known as ZengShengPing
      were also found as effective agents. Lack of activity was reported for
      cyclooxygenase inhibitors--ketorolac and celecoxib. More promising data was
      collected from animal experimental studies with chemically induced oral squamous
      cell carcinoma. Chemopreventive activity was revealed for various agents
      including plant-derived compounds like resveratrol, green and black tee
      polyphenols, as well as protocatechuic, ellagic and caffeic acids.

PMID- 22590921
TI  - [Resveratrol--phytophenol with wide activity].
AB  - Resveratrol (3,5,4'-trihydroxystilbene) is a natural phytophenol. It is found in
      many plants, but the highest concentration was detected in different grape
      derived products, especially in red wine. The substance is also an active
      ingredient of some over-the-counter diet supplements. High resveratrol popularity
      is a consequence of wide biological properties. Numbers of epidemiological and
      experimental studies have proved a complex chemiopreventive activity of
      resveratrol against various cardio-vascular disorders and cancer. Furthermore,
      the compound possesses anti-inflammatory activity and positively regulates
      glucose level and metabolism of adipose tissue. Diet rich in resveratrol promotes
      longevity and attenuates neurodegenerative diseases.

PMID- 22590923
TI  - [Two spreading states of mesenchymal cells of the human embryo in vitro].
AB  - Spreading mesenchymal cells of human embryo on plastic and type I collagens (from
      rat, sheep and bull) was studied. Spreading of the cells on collagens was
      stronger than that in the control but no differences between the different
      collagens were revealed. The cell perimeter, the spreading coefficient and the
      cell projection area on the substrate were used as morphometric parametres. The
      spreading of cells was monitored for 0.5-2 h after plating. During the spreading
      both on plastic and on collagen, the groups of small cells were revealed as
      separate subpopulations. As a whole, such cells comprehend 9 % of the cell
      population in the control and 2% in experiment. We assume that this cell type is
      associated with a special independent functional state of the cells that precedes
      cell spreading.

PMID- 22590922
TI  - [Intracellular gaseous messengers, nitric oxide, carbon monoxide and hydrogen
      sulfide participate in apoptosis regulation].
AB  - In this paper, participation of gases, nitric oxide, carbon monoxide and hydrogen
      sulfide, in cell apoptosis regulation has been analyzed according to the
      literature data and our own findings. Different mechanisms of nitric oxide
      influence on apoptotic reaction including modulation of transcription factors
      activity and increase in mitochondrion membrane permeabilisation are described.
      Brief description of the generation and signal transduction pathways of carbon
      monoxide is presented. Pro- and antiapoptotic mechanisms of hydrogen sulfide
      influence on cell fate are analyzed.

PMID- 22590924
TI  - [The secondary structure of peptides derived from the third intracellular loop of
      the serpentine type receptors and its interrelation with their biological
      activity].
AB  - We and other authors have shown that synthetic peptides corresponding to regions
      of the third intracellular loop (ICL-3) of receptors of the serpentine type are
      capable of activating G-protein signaling cascades and trigger them in the
      absence of hormone. To create on the basis of these peptides the selective
      regulators of hormonal signaling systems the relationship between their
      biological activity and secondary structure are studied. It is assumed that most
      suitable is a helical conformation, which allows the peptide effectively interact
      with signaling proteins. The aim of this study was to test the biological
      activity and secondary structure of synthesized by us linear peptides and their
      dimeric and palmitoylated analogs, corresponding to C-terminal region of the ICL
      3 of luteinizing hormone receptor (LHR) and 5-hydroxytryptamine receptor of the
      type 6 (5-HT6R). It is shown that LHR-peptides at the micromolar concentrations
      stimulate the basal activity of adenylyl cyclase (AC) and the GTP-binding of G
      proteins in the plasma membranes of rat testes, while 5-HT6R-peptides activate AC
      and G-proteins in the synaptosomal membranes of rat brain. The action of peptides
      is tissue-specific and observed in the tissues where there are homologous
      receptors. The most effective were palmitoylated peptides. LHR-peptide reduced
      the AC stimulatory effect of human chorionic gonadotropin, while 5-HT6R-peptides
      the effect of 5-HT6R-agonist, EMD-386088, and the action of the peptides was not
      found in the case of non-homologous receptors. Using circular dichroism
      spectroscopy it is shown that in neutral (pH 7) and acidic (pH 2) medium all the
      peptides are exist predominantly in the antiparallel beta-sheet (37-42%) and
      disordered conformations (33-35%). In alkaline medium (pH 10) in the case
      palmitoylated peptides the increase of the contribution of the helical
      conformation to 12-27% was observed. In the presence of trifluoroethanol (10
      80%), a helix-forming solvent, the contribution of helical conformation for the
      majority of peptides was slightly increased (for palmitoylated analogs to 14%),
      however, in this case the antiparallel beta-sheet and disordered conformation
      prevailed. The conclusion was made that the lack of clearly expressed ability to
      form helices in peptides derived the ICLs of receptors did not significantly
      affect their activity. This is consistent with proposed mechanism of peptides
      action, whereby peptide interacts with the complementary regions of homologous
      receptor that does not require the helix formation.

PMID- 22590925
TI  - [The presence and localization of heat shock protein 70 in rat mast cells].
AB  - Heat shock protein 70 (Hsp70) is considered not only as a cytosolic stress
      protein, but also as an extracellular molecule with immunomodulatory and
      signaling functions that play a role in adaptation to stress on cellular and
      systemic levels. The active involvement of mast cells in adaptation to stress may
      be associated with the presence of Hsp70 in secretory granules. Using
      immunoelectron microscopy, we showed that Hsp70 localized in secretory granules
      of rat pericardial and peritoneal mast cells. Localization of Hsp70 in rat
      perinoneal mast cells isolated by centrifugation on Percoll was confirmed by
      immunoblotting. The proposed involvement of mast cells in production of
      extracellular Hsp70 and possible functions of Hsp70 inside the mast cells
      granules are discussed.

PMID- 22590926
TI  - [The involvement of actin cytoskeleton in glutoxim and molixan effect on
      intracellular Ca(2+)-concentration in macrophages].
AB  - Glutoxim and molixan belong to new generation of disulfide-containing drugs with
      immunomodulatory, hepatoprotective and hemopoetic effect on cells. Using Fura-2AM
      microfluorimetry, two structurally distinct actin filament disrupters,
      latrunculin B and cytochalasin D, and calyculin A, which causes actin filaments
      condensation under plasmalemma, we have shown the involvement of actin
      cytoskeleton in the intracellular Ca(2+)-concentration increase induced by
      glutoxim or molixan in rat peritoneal macrophages. Morphological data obtained
      with the use of rhodamine-phalloidine have demonstrated that glutoxim and molixan
      cause the actin cytoskeleton reorganization in rat peritoneal macrophages.

PMID- 22590927
TI  - [The effect of glutoxim on Na+ transport in frog skin: the role of cytoskeleton].
AB  - Using voltage-clamp technique, the possible role of the cytoskeleton in the
      effect of pharmacological analogue of oxidized glutathione (GSSG), drug glutoxim,
      on Na+ transport in the frog Rana temporaria skin was investigated. It was shown
      for the first time that preincibation of the skin with the microtubular
      disrupter, nocodazole, actin filament disrupter, cytochalasin D or protein
      phosphatase PP1/PP2A inhibitor, calyculin A, significantly decrease the
      stimulatory effect of glutoxim on Na+ transport. The data suggest the involvement
      of microtubules and microfilaments in the regulatory effect of glutoxim on Na+
      transport in frog skin and that reorganization of actin filaments or microtubules
      leads to inhibition of stimulatory effect of glutoxim on Na+ transport in frog
      skin epithelia.

PMID- 22590928
TI  - [Imaging of surface cell antigens on the tumor sections of lymph nodes using
      fluorescence quantum dots].
AB  - The usefulness of quantum dots for the immunofluorescent detection of surface
      antigens on the lymphoid cells has been studied. To optimize quantum dots
      detection we have upgraded fluorescent microscope that allows obtaining multiple
      images from different quantum dots from one section. Specimens stained with
      quantum dots remained stable over two weeks and practically did not bleach under
      mercury lamp illumination during tens of minutes. Direct conjugates of primary
      mouse monoclonal antibodies with quantum dots demonstrated high specificity and
      sufficient sensitivity in the case of double staining on the frozen sections.
      Because of the high stability of quantum dots' fluorescence, this method allows
      to analyze antigen coexpression on the lymphoid tissue sections for diagnostic
      purposes. The spillover of fluorescent signals from quantum dots into adjacent
      fluorescent channels, with maxima differing by 40 nm, did not exceed 8%, which
      makes the spectral compensation is practically unnecessary.

PMID- 22590929
TI  - [Comparative morphology of tissues when using polypropylene and
      polytetrafluoretilen prostheses].
AB  - The synthetic mesh is widely used for treatment of hernias. We conducted a
      comparative study of the morphological pattern of inflammation, the cellular
      composition of tissues and dynamics of scar formation in mice when using implants
      "Esfil" and "Unifleks" under influence of single and double injection of cultured
      fibroblast and without such injection to the region of stents location. A more
      pronounced inflammatory reaction during the study period of investigation was
      observed in the case of "Esfil". In the late period of the study, a higher
      percentage of fibroblasts was observed in the case of the prosthesis "Unifleks"
      compared to the prosthesis "Esfil". Injection of cultured fibroblasts modifies
      the curve of the dynamics of the inflammatory process by making it smoother in
      the case of both prostheses. So, more preferred is the use of prostheses
      "Unifleks".

PMID- 22590930
TI  - [Evolutionary regularities of somatic polyploidy expansion in salivary glands of
      gastropod mollusks. V. Subclasses Opisthobranchia and Pulmonata].
AB  - Salivary glands of 25 species of euthyneural gastropod mollusks (Opisthobranchia
      and Pulmonata) have been investigated by means of histochemical methods and DNA
      cytophotometry in nuclei of cells. The cells of three basic types are
      distinguished in glandular epithelim: granular cells (with glicoproteid granular
      inclusions), mucocytes-I (with sulfatic acid mucopolysaccharides) and mucocytes
      II (with neutral and acid nonsulfatic polysaccharides and proteins) and so the
      epithelial ciliated cells and cells of the ducts. It was shown that glandular
      cells of salivary glands of all discovered mollusks' species are polyploid in
      different degree. The highest ploidy level estimated by means of DNA content in
      most of species is 64-128c. The giant polyploidy, attained to 4096c, is
      discovered in cells of salivary glands of Tritonia diomedea. The functional
      conditionality connected with features of feeding of different mollusk species
      and phylogenetic tendencies of expansion of somatic polyploidy in class
      Gastropoda are discussed. In comparison with allogenic, facultative and small
      polyploidy manifestation in Prosobranchia the obligatory polyploidization of high
      degree revealed in cells of salivary glands of Opisthobranchia and Pulmonata is
      consider to be the original cytological arogenesis. The probable causes of such
      differences are conneted with euthyneural type of organization of central nervous
      system and giant polyploidy of neurons in Opisthobranchia and Pulmonata mollusks.
      The causes, mechanisms and significance of such correlations are unclear for the
      present.

PMID- 22590931
TI  - [Sporopollenin accumulation in Nicotiana tabacum L. microspore wall during its
      development].
AB  - Accumulation of sporopollenin components in microspore wall, its polymerization
      dynamics and possible participation of reactive oxygen species (ROS) in this
      process has been studied. For this purpose fluorescent and electron microscopy
      (TEM) was used. It has been determined that phenylpropanoid components of
      sporopollenin that form the exine accumulate in the microspore cell wall at the
      middle and late tetrad stages. At the late tetrad stage, they fully cover the
      microspore surface and accumulate abundantly in aperture areas. In accordance
      with this, numerous thick sporopollenin lamellae, electron-dense and acetolysis
      resistant, emerge in aperture areas. Exine in the areas between apertures
      includes both acetolysis-resistant sporopollenin and washout components. These
      particular parts of the wall are intensively stained with fluorescent dye
      MitoSOX, which detects the presence of ROS. The staining disappeared after the
      treatment of microspore with superoxide dismutase, demonstrating the presence of
      superoxide in the exine. Superoxide easily converts to hydrogen peroxide, which
      can cause oxidative polymerization of sporopollenin components, leading to the
      formation of chemically stable biopolymer. The data obtained favor the hypothesis
      of ROS involvement in the formation of sporopollenin.

PMID- 22590932
TI  - [Nucleus DNA content measurement methods features].
AB  - We suggest a new theoretical method of the flow cytometry DNA histograms and
      apply it for Drosophila melanogaster imaginal discs cells. The model gives a
      possibility to determine the proportions of cells in G1, G2 (M) and S cell cycle
      phases. We show that the precision of G1 and G2 (M) DNA content measurements is
      limited by the precision of device zero signal arrangement. The usage of
      calculated device zero and dividing cells as the DNA content standards may
      improve the precision of DNA content measurements. We also compared the
      precisions of different DNA content methods and draw the conclusion that the
      current precisions of different methods are similar and lie within 2-6% interval.

PMID- 22590933
TI  - [Evidence and outcome].

PMID- 22590934
TI  - [The correlation of middle ear pressure variations with mastoid pneumatization
      during nitrous oxide administration].
AB  - BACKGROUND: The present study evaluated the relationship between the middle ear
      (ME) pressure increase rate (PIR) and the mastoid size as well as the effect of
      mastoid size on the incidence of nausea and vomiting during nitrous oxide (N2O)
      anesthesia. METHODS: Twelve healthy male volunteers were recruited. The extent of
      mastoid pneumatization was measured planimetrically using a mastoid X-ray
      (Schuller's view). The ears were then divided into a small or large mastoid group
      according to the median value. The ME pressure was compared just before each
      increase to 33%, 50%, and 67% N2O. Using the ME pressure curve, the PIR for the
      first peak of the curve steepness was calculated. RESULTS: Increasing the end
      tidal N2O concentration to 50% and 67% in the large mastoid group and to 33%,
      50%, and 67% in the small mastoid group significantly increased the ME pressure.
      The PIR in the ears in the large mastoid group was significantly lower and the
      incidence of nausea was 33% in the small mastoid group during 33% N2O anesthesia.
      CONCLUSIONS: A higher PIR in the ears and a higher incidence of nausea were
      observed in the small mastoid group, compared with the large mastoid group.

PMID- 22590935
TI  - [Breakdown of fat tissue and muscle protein under remifentanil anesthesia].
AB  - BACKGROUND: We investigated the efficacy of glucose infusion for the inhibition
      of breakdown of fat tissue and muscle protein under remifentanil anesthesia.
      METHODS: Twenty adult patients (ASA I or II) were enrolled in this study and
      randomized into two groups: a control group receiving acetated Ringer's solution
      without glucose (n = 10) and a glucose group receiving acetated Ringer's solution
      containing 1% glucose (n = 10). Anesthesia was induced by propofol and fentanyl
      and maintained by sevoflurane and remifentanil. Plasma concentrations of glucose
      and cortisol were measured. Acetoacetic acid and 3-hydroxybutyrate acid were
      measured as parameters for breakdown of fat tissue. Urine 3
      methylhistidine/plasma creatinine was measured as a parameter for breakdown of
      muscle protein during surgery. Data were analyzed by the unpaired t-test,
      Friedman's chi2-test, Wilcoxon's t-test and Mann-Whitney U test. P < 0.05 was
      considered significant. RESULTS: Plasma concentrations of cortisol and glucose
      were not increased in either group during the study. Plasma concentrations of
      acetoacetic acid and 3-hydroxybutyrate acid and urine 3-methylhistidine/plasma
      creatinine significantly increased in the control group but did not increase in
      the glucose group. CONCLUSIONS: Infusion of glucose suppresses breakdown of fat
      tissue and muscle protein under remifentanil anesthesia.

PMID- 22590936
TI  - [Low doses of ketamine have no effect on bispectral index during stable propofol
      remifentanil anesthesia].
AB  - BACKGROUND: Ketamine is associated with an increase in the bispectral index (BIS)
      values that can lead to an overdose of hypnotic agents. We investigated the
      effect of ketamine on BIS values during general anesthesia with a target
      controlled infusion (TCI) of propofol and infusion of remifentanil. METHODS:
      Forty-five ASA I or II patients undergoing gynecological surgery were included in
      this study. After 5 min of steady-state anesthesia (BIS at 35-45) without
      surgical stimulation, patients received either a bolus administration of ketamine
      0.2 mg x kg(-1) (LK group) or ketamine 0.5 mg x kg(-1) (HK group). Patients in
      the control group received no intervention. BIS values were recorded every minute
      until 15 min after ketamine administration. RESULTS: After ketamine
      administration, BIS value in HK group increased significantly compared with that
      at baseline. There were no significant changes for BIS values in LK group and
      control group over time. BIS values in HK group were significantly higher than
      those in the LK group and control group after ketamine injection. BIS values were
      not statistically different between LK group and control group. CONCLUSIONS:
      Under stable propofol and remifentanil anesthesia, a small dose of ketamine did
      not increase the BIS value over the next 15 min.

PMID- 22590937
TI  - [The evaluation of total body water composition during caesarean section under
      spinal anesthesia].
AB  - BACKGROUND: Hypotension is a common adverse effect of spinal anesthesia (SA).
      Preoperative fluid infusion is recommended to prevent hypotension during
      caesarean section. The aim of this study is to document relationship between
      preoperative total body water (TBW) and the amount of the vasopressors given
      intraoperatively and to evaluate the change of maternal body water composition
      (BWC). METHODS: In 57 patients scheduled for caesarean section under SA, maternal
      BWC was measured by bioelectrical impedance analysis method. SA was performed
      using 0.5% isobaric bupivacaine 2 ml and fentanyl 20 microg at L3-4
      intervertebral space. After this procedure, the impedance was measured again. We
      investigated the correlation between TBW and the amount of the vasopressor and
      the change of maternal BWC before and after SA. RESULTS: No positive linear
      correlation existed between the preoperative TBW and the amount of vasopressors
      given intraoperatively. SA produced a 3.8% increase in TBW and a 4.7% increase in
      extracellular water (ECW, P < 0.01). CONCLUSIONS: Preoperative TBW does not
      affect the amount of vasopressors given during caesarean section, which suggested
      massive fluid infusion can not always prevent hypotension after SA. A slight
      changes in TBW and ECW may be induced by SA, while the exact physiological and
      clinical significance of these observation remains to be elucidated.

PMID- 22590938
TI  - [Introduction of enhanced recovery after surgery (ERAS) protocols: reducing 3.4
      days of postoperative hospital stay].
AB  - BACKGROUND: Enhanced recovery after surgery (ERAS) protocols aim to improve
      patient care, reducing complication rates, and shortening hospital stay following
      colorectal surgery in Europe. In cooperation with colorectal surgeons, ERAS
      protocols were initially introduced in our hospital to the patients undergoing
      open colorectal resection in July 2010. METHODS: Length of postoperative hospital
      stay was compared of 139 consecutive patients undergoing open colorectal
      resection before (n = 96) and immediately after implementing ERAS (n = 43).
      RESULTS: In the ERAS group, length of postoperative hospital stay was
      significantly reduced from 12.7 +/- 7.7 to 9.3 +/- 6.2 days (P < 0.0001). Oral
      intake, one of important ERAS elements, both before and after surgery had
      dramatically changed, implying tolerance of ERAS protocol in Japan. CONCLUSIONS:
      We, anesthesiologists as perioperative physicians, can improve key elements of
      perioperative care such as patients' counseling, perioperative analgesia and
      early mobilization by collaboration with surgeons and nurses, to facilitate
      postoperative recovery.

PMID- 22590939
TI  - [Dexmedetomidine for postoperative sedation in elderly patients with cognitive
      impairment].
AB  - BACKGROUND: Dexmedetomidine (DEX) has analgesic, anxiolytic, and antidelirium
      effects, and causes little respiratory depression. Behavioral disturbances such
      as agitation, aggression, and sleep disorder are common in cognitive impairment;
      this impairment may be one of the risk factors for postoperative delirium. We
      studied the effects of postoperative DEX administration in elderly patients with
      cognitive impairment. METHODS: Ten patients with cognitive impairment, aged 70 to
      90 years, were maintained under both general and local anesthesia. We
      administered DEX (0.2-0.4 microg x kg(-1) x hr(-1)) to these patients 30 to 60
      min before the end of the operation. The dose of DEX was reduced to 0.1-0.2
      microg x kg(-1) hr(-1) by the time of extubation, and was increased in
      incremental doses 0.1 microg x kg(-1) x hr(-1) depending on postoperative
      agitation. RESULTS: Seven of 10 patients were calm; however, in 3 patients, the
      dose had to be increased by 0.1 microg x kg(-1) x hr(-1). No serious complication
      was observed, except bradycardia in 2 patients. CONCLUSIONS: Low-dose DEX is safe
      and useful for postoperative sedation in elderly patients with cognitive
      impairment.

PMID- 22590941
TI  - [Two cases of parturients with intracranical hemorrhage accompanied by seizure].
AB  - Intracranial hemorrhage during pregnancy is a rare complication, and it results
      in a high perinatal mortality rate. We recently encountered 2 cases of
      intracranial hemorrhage during pregnancy. They underwent cesarean section under
      general anesthesia. Anesthetic management is difficult because we must avoid
      hemodynamic change and increasing intracranial pressure, and we have difficult
      airway management. It is also very difficult to prepare for the prevention before
      the onset because it develops suddenly, and quick action is important. We must
      prepare tools of airway management and assemble people. In addition, it is
      important to use the hypotensive drugs which do not affect placental blood-flow
      to keep systolic blood pressure around 120-140 if it is necessary to suppress the
      rise of the blood pressure.

PMID- 22590940
TI  - [A case of endotracheal intubation in prone position utilizing PENTAX-Airwayscope
      for morbidly obese patient].
AB  - We experienced the airway management of a morbidly obese patient in prone
      position utilizing PENTAX-Airwayscope (AWS) which is a novel airway device for
      endotracheal intubation. A 29-year-old man, who was 150 kg in weight and 51.9 kg
      x m(-2) in body mass index, was scheduled for the discectomy for lumbar disc
      herniation. After the topical anesthesia with lidocaine spray, the patient lay on
      his stomach by himself on the table. Following the induction of general
      anesthesia with ketamine and dexmedetomidine in prone position, an anatomically
      curved blade (INTLOCK) was inserted to his oral cavity first, then the body of
      AWS was attached. With the patient breathing spontaneously, we successfully
      inserted the reinforced endotracheal tube. After the maintenance of anesthesia
      with continuous infusion of dexmedetomidine, ketamin and remifentanil, the
      patient awoke clearly without pain and endotracheal tube was removed safely in
      the prone position. Although the prone position is not the standard position for
      endotracheal intubation under general anesthesia, our technique could be
      performed in emergency situations.

PMID- 22590942
TI  - [Anesthetic management of a cervicoisthmic pregnancy patient undergoing cesarean
      section].
AB  - Cervicoisthmic pregnancy is a rare obstetric condition that is potentially
      dangerous for the pregnant woman due to a high risk of abortion or preterm
      delivery. We here present a 29-year-old woman with cervicoisthmic pregnancy
      undergoing cesarean section at full-term. Under combined epidural and spinal
      anesthesia, an infant was delivered alive, and the placenta was preserved without
      any forces to detach from the uterus. The surgery was completed without massive
      bleeding. The retained placenta was treated with methotrexate infusion into the
      uterus from the 6th day as well as uterine artery embolization at the 51th day
      postpartum. She subsequently required manual removal of the retained placenta
      under combined epidural and spinal anesthesia with only small bleeding. She was
      discharged from our hospital uneventfully. Meticulous preparation for massive
      bleeding and long-term treatment of the retained placenta are important in the
      perioperative management for cesarean section of a full-term patient with
      cervicoisthmic pregnancy.

PMID- 22590943
TI  - [Anesthesia for total and descending aorta replacement and aortic valve
      replacement for post-repair aneurysm of coarctation of aorta and aortic
      stenosis].
AB  - We experienced anesthesia for total arch and descending aorta replacement and
      aortic valve replacement for post-repair aneurysm of coarctation of aorta and
      aortic stenosis. Because there was possibility that post coarctectomy syndrome
      would occur after repair of coarctation of aorta, administration of depressor
      that acts on renin-angiotensin-aldosterone and careful observation were needed
      postoperatively. In consideration of the development of collateral vessels,
      preoperative imaging evaluation was added and operative method in cardiopulmonary
      bypass was adjusted. Careful preoperative evaluation is very important in cardiac
      anesthesia.

PMID- 22590944
TI  - [Anesthesia for a hemodialysis patient with HIT undergoing CABG using
      argatroban].
AB  - Anesthetic Management of CABG in a Hemodialysis patient complicated by heparin
      induced thrombocytopenia (HIT) type II is one of the different procedures in
      hemodialysis patients using heparin. An 81-year-old man receiving hemodialysis
      complicated by HIT type II was scheduled for coronary artery bypass grafting
      (CABG). Anesthesia was induced and maintained with propofol, remifentanil and
      rocuronium. During artificial cardiopulmonary bypass, activated clotting time
      (ACT) was maintained above 300 sec by in initial 0.1 mg x kg(-1) and subsequent
      2.0-7.0 microg x kg(-1) x min(-1) doses of argatroban; a direct thrombin
      inhibitor. Immediately after the completion of the external cardiopulmonary
      circulation, continuous infusion of argatroban was discontinued. Seven hours
      later ACT was restored to the preoperative level. Both intra and postoperative
      courses were uneventful.

PMID- 22590945
TI  - [A case of severe hypotension with catecholamine-resistant septic shock in the
      perioperative period].
AB  - We report general anesthesia of a 79-year-old man complicated with septic shock
      from abdominal artery graft infection. When he entered the operating room,
      intravenous dopamine, dobutamine, and noradrenaline had been administered and his
      bood pressure was 50/32 mmHg. General anesthesia was induced with inhalation of
      oxygen-sevoflurane and rocuronium, and maintained with sevoflurane-oxygen. During
      the operation, the patient's blood pressure was 40-50/30-35 mmHg, and heart rate
      decreased gradually to 50 beats x min(-1). Although various vasopressors
      (dopamine, dobutamine, noradrenaline, adrenaline, ephedrine, phenylephrine,
      atropine and vasopressin) were administered, they were not effective to improve
      severe hypotension. After the operation, we started blood purification (PMX
      DHP+CHDF), and in consequence blood pressure increased. It was thought that
      hemodynamics improved remarkably by reducing humoral mediators. In conclusion, it
      is considered that patients with septic shock should undergo immediate diagnosis
      and the source control should be performed in the minimum period, because it is
      possible that any vasopressor become ineffective when hypercytokinemia developes.

PMID- 22590946
TI  - [Use of cryoprecipitate for dilution coagulopathy in a 7-month-old infant].
AB  - We experienced a case of dilution coagulopathy successfully treated with
      cryoprecipitate. A seven-month-old male infant with tetralogy of Fallot and right
      femoral arteriovenous fistula had undergone a modified Blalock-Taussig shunt at
      63 days of age. He was scheduled to undergo complete repair of TOF and closure of
      femoral arteriovenous fistula. The patient was transferred to the operating room
      with tracheal intubation. Anesthesia was induced with midazolam and fentanyl and
      maintained with sevoflurane and fentanyl. Before cardiopulmonary bypass (CPB),
      femoral arteriovenous fistula was corrected. Then complete repair of TOF was
      performed under CPB. Massive bleeding was observed and laboratory results showed
      low plasma fibrinogen level (45 mg x dl(-1)). Cryoprecipitate 2 units were given
      and fibrinogen level was restored (171 mg x dl(-1)). Bleeding quickly slowed down
      sufficiently for weaning from CPB. The patient was separated easily from CPB on
      dopamine and dobutamine infusion. Post-CPB bleeding was minimal and the patient
      was transferred to intensive care unit. The patient was discharged from the
      hospital on postoperative day 50. In the present case, dilution coagulopathy
      occurred as a result of the combination of excessive fluid infusion due to
      massive bleeding and blood dilution due to CPB. Fresh frozen plasma could have
      been contraindicated to supplement fibrinogen because the patient's body weight
      was low. Cryoprecipitate, a highly concentrated source of fibrinogen, was
      effective for correcting fibrinogen deficit.

PMID- 22590947
TI  - [A case of bilateral recurrent laryngeal nerve palsy after thyroid surgery under
      intraoperative nerve monitoring].
AB  - A 66-year-old woman suffering from Basedow disease had total thyroidectomy under
      intraoperative monitoring (IOM) of recurrent laryngeal nerve (RLN) using
      Medtronic Xomed Nerve Integrity Monitor-2 (Medotronic, Mineapolice, Minesota,
      USA). IOM indicated a positive signal for her right RLN while the signal for her
      left RLN disappeared during the operation. During the surgery, surgeons
      identified her left RLN which was anatomically intact. During the attempted
      extubation of the endotracheal tube, the patient experienced severe dyspnea
      resulting in re-intubation. Fiber-optic examination revealed bilateral vocal cord
      immobility. On POD3, dysfunction of her vocal cord continued, therefore, she had
      tracheotomy With long-term follow up, her vocal cord function returned to normal
      on POD37 and tracheotomy tube was removed. In conclusion, positive signals of IOM
      are not always correlated with proper function of vocal cord. Therefore,
      respiratory condition should be carefully observed during postoperative period.

PMID- 22590948
TI  - [Coronary artery bypass graft (CABG) in a patient with chronic obstructive
      pulmonary disease (COPD) who showed difficulty in respiratory control].
AB  - We experienced a patient with severe COPD undergoing OPCAB who showed difficult
      perioperative respiratory and circulatory management. Since patients with severe
      COPDs are often complicated with not only respiratory but also circulatory
      problems such as right heart failure, it is necessary to assess preoperatively
      the method of intraoperative management including operative procedure.

PMID- 22590949
TI  - [A case of femoral neuropathy after radical ovariectomy].
AB  - We experienced a 55-year-old female patient who was diagnosed as femoral
      neuropathy after radical ovariectomy. An epidural catheter was introduced at T11
      12 interspace without any problems and general anesthesia was induced and
      maintained. The operation ended uneventfully. On the first postoperative day, she
      noticed hypesthesia of the inner surface of her left thigh and could not raise
      the left leg. The symptom remained after the removal of epidural catheter on the
      second postoperative day, and the influence of insertion of the epidural catheter
      on the symptom was suspected. We performed neurological examinations and found
      weakness of the left quadriceps femoris muscle, weakness of the left patellar
      reflex, and weakness of touch sensation and cold sensation and hypalgesia on the
      anterior surface of the left thigh and the inner surface of the left lower leg.
      Those findings led us to diagnose with femoral neuropathy probably due to
      abdominal retractors or the operation itself, and insertion of epidural
      anesthesia could not be the cause of neuropathy. Her symptom was ameliorated with
      a conservative therapy after four months. We should perform fine neurological
      examinations when neurological complications occur, especially when we use
      epidural catheters, and also should have the knowledge about those complications.

PMID- 22590950
TI  - [Survey of patients presented with severely difficult intubation in Hokkaido
      University Hospital (2005-2010)].
AB  - BACKGROUND: Recently, in addition to bronchofiberscope, the new equipments to
      manage difficult intubation are available. However, it is unknown whether the
      incidence of difficult intubation decreases or not. In order to determine the
      incidence of severe difficult intubation, we conducted a survey of patients who
      presented with severely difficult intubation during 2005-2010. METHODS: From data
      of patients in whom tracheal intubation was attempted in the operating rooms in
      Hokkaido university hospital from January 2005 to December 2010, the data was
      collected on the patients who presented with severely difficult intubation,
      defined as the inability to secure tracheal intubation in less than 20 min from
      induction of anesthesia. RESULTS: A total of 21,982 tracheal intubations were
      attempted during the study period. The incidence of severely difficult intubation
      was 0.3% (65 intubations for 58 patients). There was no significant difference
      among the years in the incidence of severely difficult intubation. CONCLUSIONS:
      The incidence of severely difficult intubation was 0.3% in Hokkaido university
      hospital during 2005-2010.

PMID- 22590951
TI  - [How to improve positioning of the head--the sniffing position, considered to be
      suitable for endotracheal intubation].
AB  - BACKGROUND: The sniffing position, a combination of flexion of the neck and
      extension of the head, is considered to be suitable for the performance of
      endotracheal intubation. To place a patient in this position, anesthesiologists
      usually put a pillow under a patient's occiput. However, with a regular pillow,
      the resulting extension of the head tends to be suboptimal. METHODS: In an
      attempt to improve positioning of the head, we started using "a triangular
      pillow". The name of this pillow comes from its shape in the sagittal section. A
      patient's head rests on a slope of the pillow so that it assumes an extended
      position. RESULTS: In this retrospective study, we compared the triangular pillow
      and the regular pillow employing the laryngoscopic view grade (Cormack grade) and
      times for tracheal intubation trial. We found that the triangular pillow group
      showed lower Cormack grades, compared with the regular pillow group. And in the
      first attempt, the success rate of the triangular pillow group was higher than
      that of the regular pillow group. CONCLUSIONS: The triangular pillow improves the
      laryngoscopic view and facilitates endotracheal intubation by optimizing a
      patient's head position.

PMID- 22590952
TI  - [Rapid sequence induction in pediatric patients--a questionnaire survey to the
      children's hospitals in Japan].
AB  - BACKGROUND: Details of the rapid sequence induction in children with full stomach
      in Japanese children's hospitals are not known. METHODS: We sent the
      questionnaire to the 27 pediatric anesthesia departments in Japanese children's
      hospitals and asked the practice of two scenarios of full stomach cases; an
      infant (4-week-old) presenting with pyloric stenosis and a child (3-year-old)
      with full stomach due to ileus. RESULTS: We obtained replies from 17 of 27 (63%)
      facilities. Nasogastric tube was inserted and suctioned thoroughly before the
      induction of anesthesia in all institutions. Atropine prior to the induction of
      anesthesia was more often used in infant cases (53%). Awake intubation was not
      performed in any facilities regardless of the age. Gentle mask ventilation
      between induction and tracheal intubation were more frequently performed in
      infant cases (53%). The maneuver of cricoid pressure was utilized in infants in
      only 24% of all institutions. CONCLUSIONS: We clarified details of rapid sequence
      induction in infants and children in Japanese children's hospitals. The practical
      method of rapid sequence induction was different in 2 scenarios probably due to
      the consideration of the age, diseases and conditions.

PMID- 22590953
TI  - [Trial of preoperative consultation in outpatient clinic at a medium sized
      hospital].
AB  - BACKGROUND: Sometimes surgery is cancelled due to insufficiency of preoperative
      risk management by consultation of anesthesiologist on the day before surgery. We
      reported achievement of preoperative consultation in outpatient clinic at a
      medium sized hospital for three years. METHODS: Reservation to our clinic was
      performed by surgeons, when they judged that early consultation by
      anesthesiologist was needed by various reasons, for example severe complications
      and problem of past anesthesia. RESULTS: Among 737 surgical patients, 49 patients
      (6.6%) were consulted in our clinic and surgery was cancelled in 8 patients
      (16.3%). Among 688 patients who were not consulted in our clinic, we judged that
      early consultation was needed in 12 patients (1.7%) and surgery was cancelled in
      2 patients. CONCLUSIONS: As preoperative consultation in outpatient clinic became
      appreciated, no patient was cancelled on the day before surgery. Moreover, our
      trial of preoperative consultation in outpatient clinic contributed to
      establishment of good relationship of anesthesiologists with surgeons and
      patients.

PMID- 22590954
TI  - [The efficacy of the "BURP" maneuver during laryngoscopy and training period
      necessary for residents in anesthesiology].
AB  - BACKGROUND: The "BURP" maneuver (back, upward, right lateral, pressure) improves
      the visualization of the larynx for experienced anesthesiologists during
      orotracheal intubation in patients with difficult airway. We investigated whether
      this maneuver has same efficacy for inexperienced residents in anesthesiology.
      METHODS: We compared the visual condition of the larynx using "BURP" maneuver,
      back pressure or no maneuver between 37 residents and 16 staff anesthesiologists
      in 132 patients receiving general anesthesia. Additionally, we investigated the
      effects of residents' training period on their advancements in visualization of
      the larynx. RESULTS: The "BURP" maneuver significantly improved the visualization
      with laryngoscope. The third month of the training period developed visualization
      in comparison with those of the first month. The visualization in experiencing 31
      35 patients was significantly improved than experiencing 1-10 patients.
      CONCLUSIONS: We concluded that "BURP" maneuver was effective even for
      inexperienced residents. More than two months were required for the residents to
      develop laryngoscopy skill.

PMID- 22590955
TI  - [Aging and kidney: an epidemiological review].

PMID- 22590956
TI  - [Morphological changes of the aging kidney].

PMID- 22590957
TI  - [Age-associated change of kidney function].

PMID- 22590958
TI  - [Aging and tubulo-interstitial injuries (possible implications of Klotho): renal
      senescence hypothesis].

PMID- 22590959
TI  - [Sirt1-mediated autophagy in aging kidney].

PMID- 22590960
TI  - [Autophagy and kidney aging].

PMID- 22590961
TI  - [Mycophenolate mofetil in induction and maintenance therapy for juvenile onset
      severe lupus nephritis].
AB  - OBJECTIVE: The aim of the present study was to evaluate the efficacy of
      mycophenolate mofetil (MMF) in the induction and maintenance therapy for juvenile
      onset severe lupus nephritis. METHODS: Children with severe focal, and diffuse
      proliferative lupus nephritis were treated with prednisolone (initial dose; 1
      mg/kg/day, maximum dose; 60 mg/day) and MMF (initial dose; 300 mg/m2/day,
      increased to 1 g/m2/day) for 24 months after high-dose intravenous
      methylprednisolone (30 mg/kg/day). Urinalysis was performed, and renal function,
      and albumin were evaluated. Serum anti-double-stranded DNA antibody, and also
      serum C3 and C4 were measured. The duration of induction therapy was defined as
      the initial 6 months after treatment. The duration of maintenance therapy was
      defined as 18 months after induction therapy. RESULTS: Twelve children (mean age
      12.6 +/- 1.7 years)were treated with induction therapy. With 6 months of
      induction therapy, urine protein, and serum anti-double-stranded DNA antibody,
      decreased significantly (p < 0.05), renal function improved, and albumin, serum
      C3 and C4 increased significantly (p < 0.05). Ten children received maintenance
      therapy. No patients had renal flares during maintenance therapy. The mean
      prednisolone dose was tapered to 9.2 +/- 2.3 mg/day. Among 5 patients who had a
      second biopsy after MMF therapy, 4 showed a significant reduction and one had no
      change in histology. Major infection episodes occurred in 5 patients: Herpes
      zoster in 3 patients, bacteremia in 2, and hair loss in 3, respectively. No
      patients discontinued MMF therapy. CONCLUSIONS: MMF is an effective induction and
      maintenance therapy for juvenile onset severe lupus nephritis.

PMID- 22590962
TI  - [Case of HIV-associated nephropathy accompanied by nephrotic syndrome and acute
      worsening of kidney function].
AB  - A previously healthy black man presented with acute kidney injury wtih nephrotic
      syndrome. His serum creatinine and albumin concentrations were 8.0 mg/dL and 0.4
      g/dL, respectively. Renal ultrasound demonstrated an enlarged kidney with an
      extremely high echogenic cortex. Human immunodeficiency virus (HIV) was
      serologically positive, and kidney biopsy revealed a collapsing variant of focal
      segmental glomerulosclerosis with interstitial nephritis. He was diagnosed as
      having HIV-associated nephropathy (HIVAN). Although there have been only a few
      cases with characteristic HIVAN features in Japan, the number of patients with
      HIVAN who need dialysis treatment is relatively high globally, and is expected to
      increase even in Japan. The rapid clinical course of HIVAN, along with its
      characteristic histology and the direct pathogenesis of HIV on podocytes, is
      noteworthy. We described this case with reference to some recent findings.

PMID- 22590963
TI  - Feeding patterns and growth of term infants in Eldoret, Kenya.
AB  - BACKGROUND: There are limited longitudinal data from developing countries on
      early infant feeding and growth patterns. In Kenya only 34.8% of infants are
      exclusively breastfed at 2 months. This finding is of concern, and further
      understanding of infant feeding and growth patterns is important. OBJECTIVE: To
      determine the feeding and growth patterns of Kenyan term infants during early
      infancy. METHODS: A longitudinal study was conducted. One hundred and fifty-one
      resource-constrained mother-infant pairs were recruited from the West Municipal
      Health Centre (WMHC) within 24 hours after birth, and subsequent follow-up was
      performed at the WMHC Maternal and Child Health Clinic. Data on baseline
      characteristics were collected with the use of a structured questionnaire. Data
      on nonbreastmilk liquids given to the infants and feeding patterns were gathered
      with the use of a 24-hour recall. Standard procedures were used to measure infant
      weight, recumbent length, and head circumference. World Health Organization (WHO)
      growth standards were used, and tests for variation between and within group
      means were performed, with alpha < .05 regarded as indicating significance.
      RESULTS: At 6 and 10 weeks, the prevalence of exclusive breastfeeding was 40.4%
      and 9.9%, respectively. The mothers cited "aids infant's digestion" (38%) as the
      main reason for partial breastfeeding and "breastmilk was not enough" (48%) as
      the main reason for predominant breastfeeding. Growth velocity based on weight
      was similar to that in the WHO reference group. All of the children had normal
      growth (z-score > -2). Mothers without knowledge about WHO/UNICEF early infant
      feeding recommendations and those who initiated breastfeeding more than 1 hour
      post partum were ninefold and eightfold more likely to start mixed feeding by 10
      weeks of age, respectively. CONCLUSIONS: There is a need to accelerate awareness
      of optimum infant feeding recommendations and augment the rigorous practice of
      the WHO Ten Steps to Successful Breastfeeding.

PMID- 22590964
TI  - Community-led initiative for control of anemia among children 6 to 35 months of
      age and unmarried adolescent girls in rural Wardha, India.
AB  - BACKGROUND: Studies in India have reported a high prevalence of nutritional
      anemia among children and adolescent girls. Nutritional anemia is associated with
      impaired mental, physical, and cognitive performance in children and is a
      significant risk factor for maternal mortality. OBJECTIVE: To evaluate the effect
      of a community-led initiative for control of nutritional anemia among children 6
      to 35 months of age and unmarried rural adolescent girls 12 to 19 years of age.
      METHODS: This Participatory Action Research was done in 23 villages of the
      Primary Health Centre, Anji, in Wardha District of Maharashtra. In February and
      March 2008, needs assessment was undertaken by interviewing the mothers of 261
      children and 260 adolescent girls. Hemoglobin levels of adolescent girls and
      children were measured with the use of the hemoglobin color scale. The girls were
      given weekly iron-folic acid tablets, and the children were given daily liquid
      iron prophylaxis for 100 days in a year through community participation. The
      adolescent girls and the mothers of the children and adolescent girls were also
      given nutritional education on the benefits and side effects of iron
      supplementation. In June and July 2008, follow-up assessment was performed by
      survey and force field analysis. RESULTS: There was a significant reduction in
      the prevalence of nutritional anemia from 73.8% to 54.6% among the adolescent
      girls and from 78.2% to 64.2% among the children. There was improvement in
      awareness of iron-rich food items among the adolescent girls and the mothers of
      the children. The benefits to girls, such as increase in appetite and reduction
      in scanty menses, tiredness, and weakness, acted as positive factors leading to
      better compliance with weekly iron supplementation. The benefits to children
      perceived by the mothers, such as increase in appetite, weight gain, reduction in
      irritability, and reduction in mud-eating behavior, acted as a dominant positive
      force and generated demand for iron syrup. CONCLUSIONS: The community-led
      initiative for once-weekly iron supplementation for adolescent girls and iron
      prophylaxis for children, in addition to nutritional education, improved the
      hemoglobin status of children 6 to 35 months of age and unmarried rural
      adolescent girls 12 to 19 years of age.

PMID- 22590965
TI  - New benchmarks for costs and cost-efficiency of school-based feeding programs in
      food-insecure areas.
AB  - BACKGROUND: School feeding is a popular intervention that has been used to
      support the education, health and nutrition of school children. Although the
      benefits of school feeding are well documented, the evidence on the costs of such
      programs is remarkably thin. OBJECTIVE: Address the need for systematic estimates
      of the cost of different school feeding modalities, and of the determinants of
      the considerable cost variation among countries. METHODS: WFP project data,
      including expenditures and number of schoolchildren covered, were collected for
      78 projects in 62 countries through project reports and validated through WFP
      Country Office records. Yearly project costs per schoolchild were standardized
      over a set number of feeding days and the amount of energy provided by the
      average ration. Output metrics, such as tonnage, calories, and micronutrient
      content, were used to assess the cost-efficiency of the different delivery
      mechanisms. RESULTS: The standardized yearly average school feeding cost per
      child, not including school-level costs, was US$48. The yearly costs per child
      were lowest at US$23 for biscuit programs reaching school-going children and
      highest at US$75 for take-home rations programs reaching families of schoolgoing
      children. The average cost of programs combining on-site meals with extra take
      home rations for children from vulnerable households was US$61. Commodity costs
      were on average 58% of total costs and were highest for biscuit and take-home
      rations programs (71% and 68%, respectively). Fortified biscuits provided the
      most cost-efficient option in terms of micronutrient delivery, whereas take-home
      rations were more cost-efficient in terms of food quantities delivered.
      CONCLUSIONS: Both costs and effects should be considered carefully when designing
      school feeding interventions. The average costs of school feeding estimated here
      are higher than those found in earlier studies but fall within the range of costs
      previously reported. Because this analysis does not include school-level costs,
      these findings highlight the higher nontransfer costs for programs delivering
      cooked meals in schools than for other school feeding modalities. The benchmarks
      presented here reflect the centralized WFP implementation model, which is not
      always relevant in terms of government school feeding programs, particularly
      those procuring within national boundaries using "home-grown" approaches.

PMID- 22590966
TI  - Home-based treatment of acute malnutrition in Cambodian urban poor communities.
AB  - BACKGROUND: The prevalence of malnutrition in Cambodia is among the highest in
      Southeast Asia. Until recently, there has been a consensus that the treatment and
      rehabilitation of acutely severely malnourished children should take place in
      hospitals; however, limited local health resources often place constraints upon
      the inpatient management of these children. OBJECTIVE: This study reviews the
      outcomes of a community nutrition program designed to rehabilitate children under
      the age of 5 years with moderate or severe acute malnutrition living in a poor
      urban community in Phnom Penh, Cambodia. METHODS: Clinical records of the program
      participants during the period from January 1999 to November 2006 were reviewed.
      Attainment of recovery weight-for-height z-scores, the length of time taken to
      achieve this recovery, rates of weight gain, mortality rate, and rate of default
      were determined from the data. RESULTS: One hundred fifty-nine children aged 4
      years or younger with a mean admission weight-for-height z-score of -3.3 were
      treated. The mean outcome weight-for-height z-score was -1.5. Eighty-seven
      children (55%) reached a weight-for-height z-score > or = -1 over a mean period
      of 14 weeks of rehabilitation. The average rate of weight gain was 4 g/kg/day.
      The case fatality rate was 5.6%. CONCLUSIONS: This program is an example of
      effective, community-based rehabilitation of children with moderate or severe
      acute malnutrition in an urban, Southeast Asian, non-humanitarian-relief context,
      through a combination of nutritional education, regular home visiting, and food
      support.

PMID- 22590967
TI  - Effectiveness of fortification of drinking water with iron and vitamin C in the
      reduction of anemia and improvement of nutritional status in children attending
      day-care centers in Belo Horizonte, Brazil.
AB  - BACKGROUND: Because of the high prevalence of iron-deficiency anemia in Brazil,
      individual control measures tend to be ineffective, and fortification of foods
      with iron is considered the most effective method to fight anemia. OBJECTIVE: To
      evaluate the effectiveness of fortification of drinking water with iron and
      vitamin C in the reduction of anemia in children in day-care centers in Belo
      Horizonte, Brazil. METHODS: This before-and-after study evaluated 318 children
      aged 6 to 74 months. Identification data and data on socioeconomic variables were
      collected; anthropometric and biochemical measurements were performed before and
      after 5 months of fortification of water with 5 mg of elemental iron and 50 mg of
      ascorbic acid per liter. The fortified water was used for drinking and cooking at
      the day-care center. Wilcoxon's nonparametric test was used to evaluate the
      differences in continuous variables, and McNemar's test was used to compare the
      prevalence rates of anemia. RESULTS: The prevalence of anemia decreased
      significantly from 29.3% before fortification to 7.9% at the end of the study,
      with a significant increase in hemoglobin levels. Reductions in the prevalence
      rates of stunting and underweight were observed. CONCLUSIONS: Fortification of
      water with iron and vitamin C significantly reduced the prevalence of anemia and
      improved nutritional status among children attending day-care centers.

PMID- 22590968
TI  - Consumption of micronutrient-fortified milk and noodles is associated with lower
      risk of stunting in preschool-aged children in Indonesia.
AB  - BACKGROUND: Stunting is highly prevalent in developing countries and is
      associated with greater morbidity and mortality. Micronutrient deficiencies
      contribute to stunting, and micronutrient-fortified foods are a potential
      strategy to reduce child stunting. OBJECTIVE: To examine the relationship between
      the use of fortified powdered milk and noodles and child stunting in a large,
      population-based sample of Indonesian children. METHODS: Consumption of fortified
      milk and fortified noodles was assessed in children 6 to 59 months of age from
      222,250 families living in rural areas and 79,940 families living in urban slum
      areas in Indonesia. RESULTS: The proportions of children who consumed fortified
      milk and fortified noodles were 34.0% and 22.0%, respectively, in rural families,
      and 42.4% and 48.5%, respectively, in urban families. The prevalence of stunting
      among children from rural and urban families was 51.8% and 48.8%, respectively.
      Children from rural and urban families were less likely to be stunted if they
      consumed fortified milk (in rural areas, OR = 0.87; 95% CI, 0.85 to 0.90; p <
      .0001; in urban areas, OR = 0.80; 95% CI, 0.76 to 0.85; p < .0001) or fortified
      noodles (in rural areas, OR = 0.95; 95% CI, 0.91 to 0.99;p = .02; in urban areas,
      OR = 0.95; 95% CI, 0.91 to 1.01; p = .08) in multiple logistic regression models
      adjusted for potential confounders. In both rural and urban families, the odds of
      stunting were lower when a child who consumed fortified milk also consumed
      fortified noodles, or when a child who consumed fortified noodles also consumed
      fortified milk. CONCLUSIONS: The consumption of fortified milk and noodles is
      associated with decreased odds of stunting among Indonesian children. These
      findings add to a growing body of evidence regarding the potential benefits of
      multiple micronutrient fortification on child growth.

PMID- 22590969
TI  - Validation of the Malaysian Coping Strategy Instrument to measure household food
      insecurity in Kelantan, Malaysia.
AB  - BACKGROUND: Food insecurity occurs whenever people are not able to access enough
      food at all times for an active and healthy life or when adequate and safe food
      acquired by socially acceptable ways is not available. OBJECTIVE: To validate the
      Malaysian Coping Strategy Instrument (MCSI) to measure household food insecurity
      in Kelantan, Malaysia. METHODS: A cross-sectional study was conducted on 301
      nonpregnant, nonlactating Malay women, aged between 19 and 49 years, living in
      rural and urban areas. The respondents were interviewed with the use of a
      structured questionnaire to obtain information on their demographic and
      socioeconomic characteristics, household food security, and dietary intake.
      RESULTS: Demographic and socioeconomic characteristics (household size, number of
      children, number of children attending school, household income, and per capita
      income) were significantly associated with household food-security status in
      rural and urban areas. Energy intake, fat intake, percentage of energy from fat,
      and number of servings of meat,fish, or poultry and legumes were significantly
      associated with household food-security status in rural areas. The dietary
      diversity score was significantly associated with household food-security status
      in rural and urban areas. CONCLUSIONS: Validating the MCSI in other areas of
      Malaysia as well as in similar settings elsewhere in the world before it is used
      to measure household food insecurity in the population is strongly recommended.
      In this study, the MCSI was found to be a reliable and valid measure of household
      food insecurity based on criterion-related validity, particularly in terms of
      demographic and socioeconomic characteristics and dietary diversity.

PMID- 22590970
TI  - Policy interventions to promote healthy eating: a review of what works, what does
      not, and what is promising.
AB  - Unhealthy diets can lead to various diseases, which in turn can translate into a
      bigger burden for the state in the form of health services and lost production.
      Obesity alone has enormous costs and claims thousands of lives every year.
      Although diet quality in the European Union has improved across countries, it
      still falls well short of conformity with the World Health Organization dietary
      guidelines. In this review, we classify types of policy interventions addressing
      healthy eating and identify through a literature review what specific policy
      interventions are better suited to improve diets. Policy interventions are
      classified into two broad categories: information measures and measures targeting
      the market environment. Using this classification, we summarize a number of
      previous systematic reviews, academic papers, and institutional reports and draw
      some conclusions about their effectiveness. Of the information measures, policy
      interventions aimed at reducing or banning unhealthy food advertisements
      generally have had a weak positive effect on improving diets, while public
      information campaigns have been successful in raising awareness of unhealthy
      eating but have failed to translate the message into action. Nutritional labeling
      allows for informed choice. However, informed choice is not necessarily
      healthier; knowing or being able to read and interpret nutritional labeling on
      food purchased does not necessarily result in consumption of healthier foods.
      Interventions targeting the market environment, such as fiscal measures and
      nutrient, food, and diet standards, are rarer and generally more effective,
      though more intrusive. Overall, we conclude that measures to support informed
      choice have a mixed and limited record of success. On the other hand, measures to
      target the market environment are more intrusive but may be more effective.

PMID- 22590971
TI  - Discovery and characterization of a group of fungal polycyclic polyketide
      prenyltransferases.
AB  - The prenyltransferase (PTase) gene vrtC was proposed to be involved in
      viridicatumtoxin (1) biosynthesis in Penicillium aethiopicum. Targeted gene
      deletion and reconstitution of recombinant VrtC activity in vitro established
      that VrtC is a geranyl transferase that catalyzes a regiospecific Friedel-Crafts
      alkylation of the naphthacenedione carboxamide intermediate 2 at carbon 6 with
      geranyl diphosphate. VrtC can function in the absence of divalent ions and can
      utilize similar naphthacenedione substrates, such as the acetyl-primed TAN-1612
      (4). Genome mining using the VrtC protein sequence leads to the identification of
      a homologous group of PTase genes in the genomes of human and animal-associated
      fungi. Three enzymes encoded by this new subgroup of PTase genes from Neosartorya
      fischeri, Microsporum canis, and Trichophyton tonsurans were shown to be able to
      catalyze transfer of dimethylallyl to several tetracyclic naphthacenedione
      substrates in vitro. In total, seven C(5)- or C(10)-prenylated naphthacenedione
      compounds were generated. The regioselectivity of these new polycyclic PTases
      (pcPTases) was confirmed by characterization of product 9 obtained from
      biotransformation of 4 in Escherichia coli expressing the N. fischeri pcPTase
      gene. The discovery of this new subgroup of PTases extends our enzymatic tools
      for modifying polycyclic compounds and enables genome mining of new prenylated
      polyketides.

PMID- 22590972
TI  - Centrifugation assisted microreactor enables facile integration of trypsin
      digestion, hydrophilic interaction chromatography enrichment, and on-column
      deglycosylation for rapid and sensitive N-glycoproteome analysis.
AB  - Sample handling procedures including protein digestion, glycopeptide enrichment,
      and deglycosylation have significant impact on the performance of glycoproteome
      analysis. Several glycoproteomic analysis systems were developed to integrate
      some of these sample preparation procedures. However, no microsystem integrates
      all of above three procedures together. In this work, we developed a
      glycoproteomic microreactor enabling seamless integration of all these
      procedures. In this reactor, trypsin digestion was accelerated by adding
      acetonitrile to 80%, and after acidification of protein digest by trifluoroacetic
      acid (TFA), the following hydrophilic interaction chromatography (HILIC)
      enrichment and deglycosylation were sequentially performed without any desalting,
      lyophilization, or buffer exchange steps. The total processing time could be as
      short as 1.5 h. The detection limit of human IgG as low as 30 fmol was also
      achieved. When applied to human serum glycoproteome analysis, a total number of
      92, 178, and 221 unique N-glycosylation sites were identified from three
      replicate analyses of 10 nL, 100 nL, and 1 MUL of human serum, respectively. It
      was demonstrated that the glycoproteomic microreactor based method had very high
      sensitivity and was well suited for glycoproteome analysis of minute protein
      samples.

PMID- 22590973
TI  - Copper(I)-catalyzed synthesis of 2,5-disubstituted furans and thiophenes from
      haloalkynes or 1,3-diynes.
AB  - A regioselective synthesis of 2,5-disubstituted furans using copper(I) catalyst
      from haloalkynes in a one-pot procedure has been reported. This chemistry
      proceeds through the hydration reaction of 1,3-diynes, which can be readily
      prepared from the coupling reaction of haloalkynes in the presence of CuI. The
      procedure also can be used for the facile synthesis of 2,5-disubstituted
      thiophenes.

PMID- 22590975
TI  - The effects of aggregation on electronic and optical properties of oligothiophene
      particles.
AB  - Solution processing of oligothiophene molecules is shown to produce a range of
      particles with distinct morphologies. Once isolated on a substrate, the optical
      and electronic properties of individual particles were studied. From polarized
      scanning confocal microscopy experiments, distinct particles that are
      identifiable by shape were shown to have similar emission spectra except in
      regard to the 0-0 vibronic band intensity. This suppression of the 0-0 vibronic
      band correlates to the amount of energetic disorder present in a weakly coupled H
      aggregate. The studied particles ranged from moderate to almost complete
      suppression of the 0-0 vibronic band when compared to the emission spectrum of
      the isolated molecule in solution. All particles were found to have a high degree
      of geometric order (molecular alignment) as observed from the fluorescence
      dichroism (FD) values of around 0.7-0.8 for all the studied morphologies. The
      structural and electronic properties of the particles were investigated with
      Kelvin probe force microscopy (KPFM) to measure the local contact potential (LCP)
      difference, a quantity that is closely related to the differences in
      intermolecular charge distribution between the oligothiophene particles. The LCP
      was found to vary by as much as 70 mV between different oligothiophene particles
      and a trend was observed that correlated the LCP changes with the amount of
      energetic disorder present, as signified by the suppression of the 0-0 vibronic
      peak in the emission spectra. Combined polarized scanning confocal microscopy
      studies, along with KPFM measurements, help to provide fundamental insights into
      the role of morphology, molecular packing, and intermolecular charge
      distributions in oligiothiophene particles.

PMID- 22590976
TI  - Team-based learning methods in teaching topographical anatomy by dissection.
AB  - BACKGROUND:   While the effectiveness of teaching human topographical anatomy by
      groups of medical students carrying out embalmed cadaver dissections has been
      recognized for centuries, the mechanisms by which this teaching is so effective
      have not been well described. METHODS:   In the recently reintroduced 7-week
      elective anatomy by whole body dissection course for senior medical students at
      Sydney Medical School, team-based learning (TBL) principles were used in the
      course design and implementation. In the 2011 course, 42 senior medical students
      participated. The effectiveness of TBL pedagogy was assessed by knowledge
      acquisition and retention and by administration of a questionnaire to evaluate
      the impact of the principles of this pedagogy. RESULTS:   The course produced a
      marked increase in topographical anatomical knowledge. The median pre-course
      assessment score was 9/20 (interquartile range 5) and the median post-course
      assessment score was 19.5/20 (interquartile range 1.75). The difference was
      statistically significant (P < 0.001). There was near universal agreement by
      students that five key principles of TBL (small groups, instructor selected
      allocation to groups, regular assessments, inter- and intra-group
      competitiveness, and prescribed out-of-class preparation), contributed to this
      knowledge acquisition. CONCLUSION:   The application of TBL methodology to
      teaching human anatomy by dissection enables a large group of students to have
      small group experiences without a large number of teachers. It results in
      effective acquisition of topographical anatomical knowledge and appears to
      provide better acquisition of such knowledge than the previous methods of anatomy
      teaching to which these students had been exposed.

PMID- 22590974
TI  - The intracrine renin-angiotensin system.
AB  - The RAS (renin-angiotensin system) is one of the earliest and most extensively
      studied hormonal systems. The RAS is an atypical hormonal system in several ways.
      The major bioactive peptide of the system, AngII (angiotensin II), is neither
      synthesized in nor targets one specific organ. New research has identified
      additional peptides with important physiological and pathological roles. More
      peptides also mean newer enzymatic cascades that generate these peptides and more
      receptors that mediate their function. In addition, completely different roles of
      components that constitute the RAS have been uncovered, such as that for prorenin
      via the prorenin receptor. Complexity of the RAS is enhanced further by the
      presence of sub-systems in tissues, which act in an autocrine/paracrine manner
      independent of the endocrine system. The RAS seems relevant at the cellular
      level, wherein individual cells have a complete system, termed the intracellular
      RAS. Thus, from cells to tissues to the entire organism, the RAS exhibits
      continuity while maintaining independent control at different levels. The
      intracellular RAS is a relatively new concept for the RAS. The present review
      provides a synopsis of the literature on this system in different tissues.

PMID- 22590977
TI  - CTHRC1 is upregulated by promoter demethylation and transforming growth factor
      beta1 and may be associated with metastasis in human gastric cancer.
AB  - The gene, collagen triple helix repeat containing 1 (CTHRC1), has been reported
      to increase in several kinds of human solid cancers and is associated with tumor
      invasion and metastasis. To date, the expression and function of CTHRC1 in
      gastric cancer (GC) have not been reported. The aim of this study was to
      investigate the expression levels and regulatory transcription mechanisms of
      CTHRC1 in GC. Immunohistochemical analysis revealed that CTHRC1 expression was
      markedly increased in carcinoma compared with normal gastric mucosa, chronic
      atrophic gastritis, and intestinal metaplasia (P < 0.05 for all), and this
      overexpression in tumor was related to depth of tumor invasion. Moreover, RNA
      interference-mediated knockdown and ectopic expression of CTHRC1 showed that
      CTHRC1 promoted tumor cell invasion in vitro. We then investigated the mechanisms
      underlying the aberrant expression of CTHRC1 in GC and found that CTHRC1
      expression was restored after GC cell lines were treated with the demethylating
      agent, 5-aza-2'-deoxycytidine. Transforming growth factor-beta1 led to an
      increase in levels of CTHRC1 mRNA and protein. Overall, our data revealed that
      the upregulated expression of CTHRC1 in gastric carcinogenesis contributes to
      tumor cell invasion and metastasis, and promoter demethylation and transforming
      growth factor-beta1 may co-regulate the expression of CTHRC1.

PMID- 22590979
TI  - Transplacental transfer of oseltamivir carboxylate.
AB  - OBJECTIVES: Determine the bidirectional transfer of oseltamivir carboxylate (OC)
      across term human placenta and its distribution between the tissue, maternal and
      fetal circuits. METHODS: The technique of dual perfusion of placental lobule
      (DPPL) in its recirculating mode was utilized to determine the transfer of the
      drug. OC (350 ng/mL) was co-perfused with its [(3)H]-isotope and the marker
      compound antipyrine (AP, 20 ug/mL) together with its [(14)C]-isotope. The
      concentrations of OC and any of its metabolite(s) formed during perfusion were
      determined in the tissue, maternal and fetal circuits by liquid scintillation
      spectrometry following their separation by High Performance Liquid Chromatography
      (HPLC). RESULTS: The distribution of OC following its perfusion in the Maternal
      to-Fetal direction for 4 h was as follows: 21 +/- 4% of the drug was transferred
      to the fetal circuit, 13 +/- 5% was retained by the perfused lobule, and 66 +/-
      4% remained in the maternal circuit. The normalized transfer of OC to that of AP
      (Clearance index) in the maternal-to-fetal direction was (0.47 +/- 0.11) and was
      not different from its transfer from the fetal-to-maternal direction (0.47 +/-
      0.06) suggesting that involvement of placental efflux transporters is unlikely.
      CONCLUSIONS: OC crosses human placenta. As the transfer rate of OC is 47% of the
      freely diffusible AP, it is likely that fetus could be exposed to OC during
      pregnancy.

PMID- 22590980
TI  - Application of the Rodriguez-Pattenden photo-ring contraction: total synthesis
      and configurational reassignment of 11-gorgiacerol and 11-epigorgiacerol.
AB  - A stereospecific photochemical ring contraction was used as the key step in the
      first total synthesis of the marine pseudopteranyl diterpene 11-gorgiacerol and
      its 11-epimer. The synthesis allowed the correction of the configurations that
      had been misassigned in the literature. In addition, some novel pseudopteranyl
      derivatives have been made.

PMID- 22590978
TI  - The ORF2 glycoprotein of hepatitis E virus inhibits cellular NF-kappaB activity
      by blocking ubiquitination mediated proteasomal degradation of IkappaBalpha in
      human hepatoma cells.
AB  - BACKGROUND: Nuclear factor kappa B (NF-kappaB) is a key transcription factor that
      plays a crucial role in host survival during infection by pathogens. Therefore,
      it has been a priority of many pathogens to manipulate the cellular NF-kappaB
      activity in order to create a favorable environment for their survival inside the
      host. RESULTS: We observed that heterologous expression of the open reading frame
      2 (ORF2) protein in human hepatoma cells led to stabilization of the cellular I
      kappa B alpha (IkappaBalpha) pool, with a concomitant reduction in the nuclear
      localization of the p65 subunit of NF-kappaB and inhibition of NF-kappaB
      activity. Although basal or TPA induced phosphorylation of IkappaBalpha was not
      altered, its ubiquitination was markedly reduced in ORF2 expressing cells.
      Further analysis revealed that ORF2 protein could directly associate with the F
      box protein, beta transducin repeat containing protein (betaTRCP) and ORF2 over
      expression resulted in reduced association of IkappaBalpha with the SKP1 and CUL1
      components of the SCFbetaTRCP complex. Chromatin immunoprecipitation (ChIP) assay
      of the proximal promoter regions of MHC-I heavy chain and IL-8 genes using p65
      antibody and LPS stimulated ORF2 expressing cell extract revealed decreased
      association of p65 with the above regions, indicating that ORF2 inhibited p65
      binding at endogenous promoters. CONCLUSIONS: In this report we suggest a
      mechanism by which ORF2 protein of HEV may inhibit host cell NF-kappaB activity
      during the course of a viral infection.

PMID- 22590981
TI  - Click chemistry on a ruthenium polypyridine complex. An efficient and versatile
      synthetic route for the synthesis of photoactive modular assemblies.
AB  - In this Communication, we present the synthesis and use of [Ru(bpy)(2)(bpy
      CCH)](2+), a versatile synthon for the construction of more sophisticated dyads
      by means of click chemistry. The resulting chromophore-acceptor or -donor
      complexes have been studied by flash photolysis and are shown to undergo
      efficient electron transfer to/from the chromophore. Additionally, the
      photophysical and chemical properties of the original chromophore remain intact,
      making it a very useful component for the preparation of visible-light-active
      dyads.

PMID- 22590982
TI  - Effect of duration of breastfeeding on neuropsychological development at 10 to 12
      years of age in a cohort of healthy children.
AB  - AIM: The aim of this article was to explore the effect of duration of
      breastfeeding on neurocognitive development. METHOD: The long-term effect of
      breastfeeding on neurodevelopment was examined through a battery of
      neuropsychological tests in 1403 children (693 females, 710 males; mean age 11 y
      9mo [SD 6mo], range: 10y 3mo-12y 8mo) who were originally recruited at 6 to 12
      weeks of age for a clinical trial on acellular pertussis vaccines. An estimated
      IQ was obtained from scores of the vocabulary, similarities, block design, and
      coding tests. Breastfeeding data had been prospectively collected throughout the
      first year of life. Duration of exclusive breastfeeding was defined as the time
      during which children received breast milk without receiving any supplemental
      formula or food. Children were assessed at 10 to 12 years of age. We adjusted the
      analysis on test scores for multiple potential confounders. RESULTS: Multivariate
      analysis showed a significant association between exclusive breastfeeding
      duration and test scores in the vocabulary (odds ratio [OR] 0.05; confidence
      interval [CI] 0.00-0.10; p=0.04) and similarities (OR 0.06; CI 0.01-0.11; p=0.03)
      tests. These associations have a negligible effect size, however. Scores on one
      writing praxis test subcategory decreased with increasing duration of both
      exclusive breastfeeding (OR -0.06; CI -0.11 to -0.01; p=0.03) and breastfeeding
      irrespective of consumption of other foods (OR -0.06; CI -0.11 to -0.01; p=0.03).
      A negative association was also found between one subcategory of the California
      verbal learning test and breastfeeding duration longer than 6 months (OR -0.21;
      CI -0.42 to -0.01; p=0.04). INTERPRETATION: Breastfed healthy children may
      perform better on neuropsychological tests in the language domain at 10 to 12
      years of age. However, the effect of breast milk on neuropsychological
      performance in healthy children may have a limited clinical relevance and is
      confounded by parental education.

PMID- 22590983
TI  - Symptoms and esophageal motility based on phenotypic findings of scleroderma.
AB  - Scleroderma esophagus is characterized by ineffective peristalsis and reduced
      esophageal sphincter pressure. Esophageal disease in scleroderma can precede
      cutaneous manifestations and has been associated with Raynaud's phenomenon (RP)
      and pulmonary fibrosis (PF). The objective of the study is to evaluate the impact
      of cutaneous findings, RP, and PF on demographics, symptoms, and esophageal
      motility in patients with scleroderma. Scleroderma patients with esophageal
      involvement were included after review of esophageal manometries and charts over
      a 6-year period. High-resolution esophageal manometry was performed. Patients
      completed a symptom questionnaire. The study enrolled 28 patients (22 females;
      mean age 50.3 +/- 12.8 years) with scleroderma esophagus. Patients without skin
      involvement (n= 12) reported more severe heartburn (P= 0.02), while those with
      cutaneous findings (n= 16) had more frequent dysphagia with solids (P= 0.02).
      Patients with RP (n= 22) had lower amplitude of distal esophageal contractions
      (P= 0.01) than those without RP (n= 6). Patients with PF (n= 11) reported more
      severe coughing and wheezing (both P= 0.03) than those without lung disease (n=
      17). This study highlights subgroups of patients with scleroderma esophagus
      according to phenotypic findings of dermatologic changes, RP, and PF. Heartburn
      and dysphagia are important symptoms that may be associated with different stages
      of disease progression based on skin changes in scleroderma. RP was associated
      with greater esophageal dysmotility. Coughing and wheezing were more severe in
      patients with PF.

PMID- 22590984
TI  - Worldwide genetic relationships of pigs as inferred from X chromosome SNPs.
AB  - The phylogeography of the porcine X chromosome has not been studied despite the
      unique characteristics of this chromosome. Here, we genotyped 59 single
      nucleotide polymorphisms (SNPs) in 312 pigs from around the world, representing
      39 domestic breeds and wild boars in 30 countries. Overall, widespread commercial
      breeds showed the highest heterozygosity values, followed by African and American
      populations. Structuring, as inferred from FST and analysis of molecular
      variance, was consistently larger in the non-pseudoautosomal (NPAR) than in the
      pseudoautosomal regions (PAR). Our results show that genetic relationships
      between populations can vary widely between the NPAR and the PAR, underscoring
      the fact that their genetic trajectories can be quite different. NPAR showed an
      increased commercial-like genetic component relative to the PAR, probably because
      human selection processes to obtain individuals with high productive parameters
      were mediated by introgressing boars rather than sows.

PMID- 22590985
TI  - Serum superoxide dismutase, a potential predictor for radiation pneumonitis
      following chemoradiotherapy in non-small cell lung cancer patients.
AB  - PURPOSE: To explore serum superoxide dismutase (SOD) for predicting radiation
      pneumonitis (RP) in non-small cell lung cancer patients following
      chemoradiotherapy. METHODS: Serum levels for SOD were measured by enzyme-linked
      immunosorbent assays prior to radiation therapy (Pre-RT) and post 40 Gy/4 weeks
      during the treatment (Pos-RT). RESULTS: SOD concentrations after delivery of 40
      Gy/4 weeks was associated with the development of RP. The best predictive ability
      of SOD was observed for a cut-off value of 56 unit/ml, with a sensitivity of 0.80
      (95% CI 0.28-0.99), and a specificity of 0.67 (95% CI 0.43-0.65) (p = 0.040).
      CONCLUSION: Serum SOD may be a potential predictor for RP, which need to be
      further verified.

PMID- 22590986
TI  - Psychometric properties of the Dutch version of the American Nursing Activity
      Scale in an intensive care unit.
AB  - AIM: To report the development and psychometric testing of the Dutch version of
      the Nursing Activity Scale in a Dutch intensive care unit nursing population.
      BACKGROUND: The Nursing Activity Scale developed by Schutzenhofer measures
      professional clinical autonomy, by inquiring about the nurses' intention to
      exercise their own clinical decisions. This autonomy is increasingly relevant due
      to the ongoing professionalization, nurses increasingly have to make their own
      clinical decisions. DESIGN: Instrument development. METHOD: The study was
      conducted from November 2007-February 2008 and consisted of the following steps:
      translation, expert panel content validation, reliability testing and further
      content validation, test-retest stability examination, additional internal
      consistency, and validity assessment. RESULTS: After the first reliability
      testing two items seen to describe a situation not applicable to intensive care
      unit nursing in the Netherlands were deleted from the questionnaire. In the test
      retest stability assessment the intra class correlation coefficient was 0.76. The
      Cronbach's alpha of the final questionnaire was 0.82. The alphas of the
      subsamples with higher scores were significantly different from those with lower
      scores, supporting the validity of the weighing of the items. CONCLUSION.: The
      Dutch version of the nursing activity scale consists of 28 items and provides the
      opportunity to measure professional clinical autonomy for Dutch intensive care
      nurses using a well-established method.

PMID- 22590988
TI  - Hematuria in a runner after treatment with whole body vibration: a case report.
AB  - The use of whole body vibration (WBV) for therapeutic purposes is far from being
      standardized and the training protocols reported in the literature vary
      considerably. Currently, the optimal threshold for a beneficial effect is
      undetermined, and caution regarding potential health risks due to WBV is always
      necessary. In this case report, we present a 34-year-old otherwise healthy elite
      athlete (steeplechase runner) who suffered two episodes of hematuria (HT) after
      WBV training. Shortly after the third WBV, he had an episode of bright red urine.
      Seven days later, following the next WBV session (and again before his daily
      running session), a reddish-colored urine reappeared. Our patient was advised to
      stop WBV training and to take fluid before and during exertion. He did not
      experience any episode of HT during a 1-year follow-up with periodic check-ups,
      in spite of the continuation of his sporting career. The concomitance of the two
      types of trauma - daily running and WBV - could have been critical in this case
      for producing HT. In particular, we think that platforms providing side
      alternating vibration (such as the Galileo platform) may pose some health risks
      if the feet are positioned too far from the axis of rotation.

PMID- 22590987
TI  - Volatile generation in bell peppers during frozen storage and thawing using
      selected ion flow tube mass spectrometry (SIFT-MS).
AB  - To determine volatile formation during storage and thawing, whole, pureed,
      blanched, and raw green and red bell peppers (Capsicum annuum) were frozen
      quickly or slowly then stored at -18  degrees C for up to 7 mo, with and without
      SnCl(2) addition during thawing. Headspace analysis was performed by a Selected
      Ion Flow Tube Mass Spectrometer (SIFT-MS). After blanching, (Z)-3-hexenal had a
      large significant decrease in concentration since it is a heat labile compound
      while most other volatiles did not change in concentration. The freezing process
      increased volatile levels in the puree only. Slow freeze peppers had higher
      levels of some LOX generated volatiles during storage than quick freeze. During
      frozen storage of blanched samples (E)-2-hexenal, (Z and E)-hexen-1-ol, and (E)-2
      pentenal increased likely because of nonenzymatic autoxidation of fatty acids
      while other volatiles remained constant. In Raw Whole peppers, (Z)-3-hexenal,
      hexanal, and 2-pentylfuran were generated during storage likely because the LOX
      enzyme is still active during frozen storage. However, blanched samples had
      higher concentrations of (E)-2-hexenal, (Z and E)-hexen-1-ol, 1-penten-3-one, and
      (E)-2-heptenal because of enzymatic destruction of these volatiles in the raw
      samples. The levels of many of the volatiles in the raw samples, including (Z)-3
      hexenal, (E)-2-hexenal, (Z and E)-hexen-1-ol, hexanal, (E)-2-pentenal, and 2
      pentylfuran, appeared to peak around 34 d after freezing. Pureed samples had
      significantly higher levels of volatiles than the whole samples, and volatiles
      peaked earlier. Green bell pepper volatile levels were always higher than red
      bell pepper. Significantly higher volatile formation occurred during thawing than
      it did during frozen storage. PRACTICAL APPLICATION: Studying and monitoring the
      headspace volatiles with a SIFT-MS can give information that will help
      manufacturers better understand how the volatiles in bell peppers change during
      frozen storage. This will give valuable information to processors on how to
      minimize volatile changes during storage of frozen peppers.

PMID- 22590990
TI  - Prevalence of coccidial infection in dairy cattle in Shanghai, China.
AB  - The prevalence of coccidial infections in dairy cattle was examined in Shanghai
      from November 2010 to March 2011. In total, 626 fecal samples from 24 dairy farms
      were examined; oocysts were identified to the species level based on
      morphological features. All herds were infected with Eimeria species. The overall
      prevalence of coccidia was 47.1%, with the highest prevalence in <4-mo-old calves
      (51.8%) and the lowest in >12-mo-old cattle (27.0%). The number of oocysts per
      gram of feces was significantly higher in young calves than in weaners and
      adults. Ten species of Eimeria were identified, among which Eimeria
      ellipsoidalis, Eimeria bovis, Eimeria zuernii, and Eimeria alabamensis were the
      predominant species. Concurrent infection with 2-8 species was common.

PMID- 22590991
TI  - Patterns of compliance with prenatal iron supplementation among Peruvian women.
AB  - Prenatal iron supplementation is recommended to control anaemia during pregnancy.
      Low compliance and side effects have been claimed as the main obstacles for
      adequate impact of the supplementation. As part of a double-blind supplementation
      study carried out in a hospital located in a shantytown in Lima, Peru, we
      monitored compliance throughout pregnancy and evaluated factors associated with
      variation in compliance over time. Overall, 985 pregnant women were enrolled in a
      supplementation study that was administered through their prenatal care from 10
      to 24 weeks of gestation until 4 weeks postpartum. They received 60 mg iron and
      250 ug folate with or without 15 mg zinc. Women had monthly care visits and were
      also visited weekly to query regarding compliance, overall health status, and
      potential positive and negative effects of supplement consumption. Median
      compliance was 79% (inter-quartile range: 65-89%) over pregnancy, and the median
      number of tablets consumed was 106 (81-133). Primpara had lower average
      compliance; positive health reports were associated with greater compliance, and
      negative reports were associated with lower compliance. There was no difference
      by type of supplement. Women with low initial compliance did achieve high
      compliance by the end of pregnancy, and women who reported forgetting to take the
      supplements did have lower compliance. Compliance was positively associated with
      haemoglobin concentration at the end of pregnancy. In conclusion, women comply
      highly with prenatal supplementation within a prenatal care model in which
      supplies are maintained and reinforcing messages are provided.

PMID- 22590992
TI  - Completely superhydrophobic PDMS surfaces for microfluidics.
AB  - This study presents a straightforward two-step fabrication process of durable,
      completely superhydrophobic microchannels in PDMS. First, a composite material of
      PDMS/PTFE particles is prepared and used to replicate a master microstructure.
      Superhydrophobic surfaces are formed by subsequent plasma treatment, in which the
      PDMS is isotropically etched and PTFE particles are excavated. We compare the
      advancing and receding contact angles of intrinsic PDMS samples and composite
      PTFE/PDMS samples (1 wt %, 8 wt %, and 15 wt % PTFE particle concentration) and
      demonstrate that both the horizontal and vertical surfaces are indeed
      superhydrophobic. The best superhydrophobicity is observed for samples with a
      PTFE particle concentration of 15 wt %, which have advancing and receding contact
      angles of 159 degrees  +/- 4 degrees  and 158 degrees  +/- 3 degrees ,
      respectively.

PMID- 22590993
TI  - Creutzfeldt-Jakob disease cluster in the health area of Meixoeiro Hospital.
AB  - OBJECTIVE: Galicia is the Spanish region in which most bovine spongiform
      encephalopathy cases have been registered. Meixoeiro Hospital is included in the
      Galician Health Service (SERGAS). The aim of the study was to analyze the
      clinical and epidemiological characteristics of Creutzfeldt-Jakob disease (CJD)
      in the health area of Meixoeiro Hospital and to identify possible specific risk
      factors to the general public. METHODS: All incident cases of CJD were identified
      in the health area of Meixoeiro Hospital (187,877 inhabitants) over a 14-year
      period, 1997-2010, and classified according to WHO diagnostic criteria. We
      obtained clinical detail and epidemiological information on all cases. Crude and
      age-specific incidence rates were calculated. A review of surgical or invasive
      medical procedures was undertaken. RESULTS: We diagnosed 12 patients with CJD, 10
      sporadic CJD (sCJD), and two genetic CJD (gCJD). No iatrogenic or variant CJD was
      detected. According to Poisson distribution, 3.9 CJD cases would be expected for
      our area over the 14 years researched. The average yearly mortality rate from CJD
      was 4.6 cases per million (3.8 from sCJD and 0.8 from gCJD). Eight patients (67%)
      underwent at least one surgical or invasive medical procedure. Sixteen of twenty
      seven (59%) of these procedures were undertaken in Meixoeiro Hospital.
      CONCLUSIONS: The incidence of CJD in the health area of Meixoeiro Hospital is
      three times higher than expected. The hypothesis that at least some cases of sCJD
      are apparently because of covert transmission or zoonosis events should not be
      formally refuted and might explain the high rate found.

PMID- 22590994
TI  - Analysis of the tegument of Zygocotyle lunata (Trematoda: Paramphistomidae)
      adults by scanning electron microscopy.
AB  - Paramphistomiasis is a parasitic disease caused by various species of the
      Paramphistomidae. These species mainly affect domestic and wild ruminants; the
      economic impact of these diseases is often underestimated. Traditionally, the
      identification of paramphistomes has been difficult and has been based on
      morphological aspects such as the body shape, the position of the esophagus and
      cecae, or the tegumental papillae. Despite the many investigations regarding the
      tegumental papillae for other paramphistomes, very few efforts have been made
      using Zygocotyle lunata, partly because many authors differ with respect to the
      importance of papillae in the classification of paramphistomids. Herein, we
      characterize by scanning electron microscopy new tegumental papillae not
      previously described on the tegument of 3-wk-old Z. lunata adults obtained from
      mice. Three morphologically different papillae (rosette, ciliated, and conical
      papillae) were observed and are described. Based on these results, we assert that
      the newly recognized morphological features should be used for species
      differentiation in the future in addition to the new molecular techniques.

PMID- 22590995
TI  - miRNA expression profiling for identification of potential breast cancer
      biomarkers.
AB  - To identify micro RNA (miRNA) biomarker candidates for early detection of breast
      cancer and detection of minimal residual breast cancer, we performed miRNA
      expression profiling in pooled RNA samples from breast tumors, and from bone
      marrow mononuclear cells, peripheral blood mononuclear cells and plasma from
      healthy controls. We found substantially higher levels of five miRNAs in the
      breast tumors compared to the normal samples. However, validation of these miRNA
      levels, and seven other candidates selected from the literature, in individual
      samples from healthy controls and patients with non-metastatic breast cancer did
      not suggest further examination of their biomarker potential.

PMID- 22590996
TI  - Variable mesophyll conductance revisited: theoretical background and experimental
      implications.
AB  - The CO(2)  concentration at the site of carboxylation inside the chloroplast
      stroma depends not only on the stomatal conductance, but also on the conductance
      of CO(2)  between substomatal cavities and the site of CO(2)  fixation. This
      conductance, commonly termed mesophyll conductance (g(m) ), significantly
      constrains the rate of photosynthesis. Here we show that estimates of g(m)  are
      influenced by the amount of respiratory and photorespiratory CO(2)  from the
      mitochondria diffusing towards the chloroplasts. This results in an apparent
      CO(2)  and oxygen sensitivity of g(m)  that does not imply a change in intrinsic
      diffusion properties of the mesophyll, but depends on the ratio of mitochondrial
      CO(2)  release to chloroplast CO(2)  uptake. We show that this effect (1) can
      bias the estimation of the CO(2)  photocompensation point and non
      photorespiratory respiration in the light; (2) can affect the estimates of
      ribulose 1.5-bisphosphate carboxylase/oxygenase (Rubisco) kinetic constants in
      vivo; and (3) results in an apparent obligatory correlation between stomatal
      conductance and g(m) . We further show that the amount of photo(respiratory)
      CO(2)  that is refixed by Rubisco can be directly estimated through measurements
      of g(m) .

PMID- 22590997
TI  - The effects of translocation-induced isolation and fragmentation on the cultural
      evolution of bird song.
AB  - Understanding the divergence of behavioural signals in isolated populations is
      critical to knowing how certain barriers to gene flow can develop. For many bird
      species, songs are essential for conspecific recognition and mate choice.
      Measuring the rate of song divergence in natural populations is difficult, but
      translocations of endangered birds to isolated islands for conservation purposes
      can yield insights, as the age and source of founder populations are completely
      known. We found significant and rapid evolution in the structure and diversity of
      bird song in North Island saddlebacks, Philesturnus rufusater, in New Zealand,
      with two distinct lineages evolving in < 50 years. The strong environmental
      filters of serial translocations resulted in cultural bottlenecks that generated
      drift and reduced song variability within islands. This rapid divergence coupled
      with loss of song diversity has important implications for the behavioural
      evolution of this species, demonstrating previously unrecognised biological
      consequences of conservation management.

PMID- 22590998
TI  - Does vaginal preparation with povidone-iodine prior to caesarean delivery reduce
      the risk of endometritis? A randomized controlled trial.
AB  - OBJECTIVE: The purpose of the present study was to determine whether the vaginal
      preparation with povidone-iodine prior to caesarean delivery decreased the
      incidence of postpartum endometritis. METHODS: The present study was a
      prospective randomized controlled trial in which subjects received a vaginal
      preparation with povidone-iodine solution immediately prior to caesarean delivery
      or received no vaginal preparation. The primary outcome measure was the rate of
      postpartum endometritis. RESULTS: A significant decrease in post-caesarean
      endometritis was noted in the group that received the povidone-iodine vaginal
      preparation (n = 334) compared with the control group (n = 336) [6.9 vs. 11.6%;
      RR = 1.69; 95% CI = 1.03-2.76]. No statistically significant differences in the
      incidence of endometritis were noted between the experimental and control groups
      among women who were not in labor at the time of the caesarean delivery [9.2 vs.
      8.6%; RR = 1.05; 95% CI = 0.58-1.90], and no differences were found between
      groups when women with ruptured membranes were excluded from the analysis [9.6
      vs. 6.7%; RR = 1.39; 95% CI = 0.78-2.47]. CONCLUSIONS: Vaginal preparation with
      povidone-iodine solution immediately prior to a caesarean delivery reduces the
      risk of post-operative endometritis. This preemptive measure was only found to be
      beneficial in women whose membranes had ruptured and those who were in labor
      prior to caesarean surgery.

PMID- 22591000
TI  - Hole transfer in LNA and 5-Me-2'-deoxyzebularine-modified DNA.
AB  - We report the measurement of hole-transfer rate constants (k(ht)) in locked
      nucleic acid (LNA) and 5-Me-2'-deoxyzebularine (B)-modified DNA. LNA
      modification, which makes DNA more rigid, caused a decrease of more than 2 orders
      of magnitude in k(ht), whereas B modification, which increases DNA flexibility,
      increased k(ht) by more than 20-fold. The present results clearly showed that
      hole-transfer efficiency in DNA can be increased by increasing DNA flexibility.

PMID- 22591001
TI  - Ultraclean derivatized monodisperse gold nanoparticles through laser drop
      ablation customization of polymorph gold nanostructures.
AB  - We report a novel nanosecond laser ablation synthesis for spherical gold
      nanoparticles as small as 4 nm in only 5 s (532 nm, 0.66 J/cm(2)), where the
      desired protecting agent can be selected in a protocol that avoids repeated
      sample irradiation and undesired exposure of the capping agent during ablation.
      This method takes advantage of the recently developed synthesis of clean
      unprotected polymorph and polydisperse gold nanostructures using H(2)O(2) as a
      reducing agent. The laser drop technique provides a unique tool for delivering
      controlled laser doses to small drops that undergo assisted fall into a solution
      or suspension of the desired capping agent, yielding monodisperse custom
      derivatized composite materials using a simple technique.

PMID- 22591002
TI  - Infant difficulty and early weight gain: does fussing promote overfeeding?
AB  - Authors have recently suggested that difficult temperament in infancy may be
      associated with rapid weight gain, but no previous studies actually report
      associations between temperament and feeding as a response to infant distress.
      The purpose of the present study was to examine whether greater infant difficulty
      elicits more feeding, which in turn leads to more rapid weight gain in early
      infancy. One hundred fifty-four mother-infant pairs were visited at 3 and 6
      months in their homes. Besides anthropometric measures, mothers kept a 24-h diary
      of their infants' sleep, cry and feed patterns, and answered questions regarding
      feeding and infant difficultness. The results showed that feeding occurred as a
      response to nearly half (48%) of the crying intervals recorded, though it more
      often occurred in the absence of crying (83%). Mothers were most likely to report
      holding or rocking their infant as the first strategy they would employ if their
      baby fussed or cried. A regression analysis that included crying, feeding,
      weaning, sleep and infant weight revealed maternal reports of numbers of feeds
      per day as the only variable that predicted weight gain from 3 to 6 months.
      Infant crying is often followed by feeding, and more frequent feeding may promote
      more rapid weight gain. However, feeding frequency in the first few months
      appears to be more a matter of maternal discretion than a yoked response to
      temperamental difficulty. This does not preclude the possibility that overfeeding
      in later infancy could be tied to temperamental difficulty and subsequently
      related to overweight in early childhood. 

PMID- 22591003
TI  - Near-infrared-emitting squaraine dyes with high 2PA cross-sections for
      multiphoton fluorescence imaging.
AB  - Designed to achieve high two-photon absorptivity, new near-infrared (NIR)
      emitting squaraine dyes, (E)-2-(1-(2-(2-methoxyethoxy)ethyl)-5-(3,4,5
      trimethoxystyryl)-1H-pyrrol-2-yl)-4-(1-(2-(2-methoxyethoxy)ethyl)-5-(3,4,5
      trimethoxystyryl)-2H-pyrrolium-2-ylidene)-3-oxocyclobut-1-enolate (1) and (Z)-2
      (4-(dibutylamino)-2-hydroxyphenyl)-4-(4-(dibutyliminio)-2-hydroxycyclohexa-2,5
      dienylidene)-3-oxocyclobut-1-enolate (2), were synthesized and characterized.
      Their linear photophysical properties were investigated via UV-visible absorption
      spectroscopy and fluorescence spectroscopy in various solvents, while their
      nonlinear photophysical properties were investigated using a combination of two
      photon induced fluorescence and open aperture z-scan methods. Squaraine 1
      exhibited a high two-photon absorption (2PA) cross-section (delta2PA), ~20 000 GM
      at 800 nm, and high photostability with the photochemical decomposition quantum
      yield one order of magnitude lower than Cy 5, a commercially available
      pentamethine cyanine NIR dye. The cytotoxicity of the squaraine dyes were
      evaluated in HCT 116 and COS 7 cell lines to assess the potential of these probes
      for biomedical imaging. The viability of both cell lines was maintained above 80%
      at dye concentrations up to 30 MUM, indicating good biocompatibility of the
      probes. Finally, one-photon fluorescence microscopy (1PFM) and two-photon
      fluorescence microscopy (2PFM) imaging was accomplished after incubation of
      micelle-encapsulated squaraine probes with HCT 116 and COS 7 cells, demonstrating
      their potential in 2PFM bioimaging. 

PMID- 22591004
TI  - Existential issues among nurses in surgical care--a hermeneutical study of
      critical incidents.
AB  - AIMS: To report a qualitative study conducted to gain a deeper understanding of
      surgical nurses' experiences of existential care situations. Background. 
      Existential issues are common for all humans irrespective of culture or religion
      and constitute man's ultimate concerns of life. Nurses often lack the strategies
      to deal with patients' existential issues even if they are aware of them. DESIGN:
      This is a qualitative study where critical incidents were collected and analysed
      hermeneutically. METHODS: During June 2010, ten surgical nurses presented 41
      critical incidents, which were collected for the study. The nurses were first
      asked to describe existential care incidents in writing, including their own
      emotions, thoughts, and reactions. After 1-2 weeks, individual interviews were
      conducted with the same nurses, in which they reflected on their written
      incidents. A hermeneutic analysis was used. FINDINGS: The majority of incidents
      concerned nurses' experiences of caring for patients' dying of cancer. In the
      analysis, three themes were identified, emphasizing the impact of integration
      between nurses' personal self and professional role in existential care
      situations: inner dialogues for meaningful caring, searching for the right path
      in caring, and barriers in accompanying patients beyond medical care. CONCLUSION:
      Findings are interpreted and discussed in the framework of Buber's philosophy of
      the relationships I-Thou and I-It, emphasizing nurses' different relationships
      with patients during the process of caring. Some nurses integrate their personal
      self into caring whereas others do not. The most important finding and new
      knowledge are that some nurses felt insecure and were caught somewhere in between
      I-Thou and I-It.

PMID- 22591005
TI  - Synthesis and antisense properties of fluoro cyclohexenyl nucleic acid (F-CeNA),
      a nuclease stable mimic of 2'-fluoro RNA.
AB  - We report the design and synthesis of 2'-fluoro cyclohexenyl nucleic acid (F
      CeNA) pyrimidine phosphoramidites and the synthesis and biophysical, structural,
      and biological evaluation of modified oligonucleotides. The synthesis of the
      nucleoside phosphoramidites was accomplished in multigram quantities starting
      from commercially available methyl-D-mannose pyranoside. Installation of the
      fluorine atom was accomplished using nonafluorobutanesulfonyl fluoride, and the
      cyclohexenyl ring system was assembled by means of a palladium-catalyzed Ferrier
      rearrangement. Installation of the nucleobase was carried out under Mitsunobu
      conditions followed by standard protecting group manipulations to provide the
      desired pyrimidine phosphoramidites. Biophysical evaluation indicated that F-CeNA
      shows behavior similar to that of a 2'-modified nucleotide, and duplexes with RNA
      showed slightly lower duplex thermostability as compared to that of the more
      rigid 3'-fluoro hexitol nucleic acid (FHNA). However, F-CeNA modified
      oligonucleotides were significantly more stable against digestion by snake venom
      phosphodiesterases (SVPD) as compared to unmodified DNA, 2'-fluoro RNA (FRNA), 2'
      methoxyethyl RNA (MOE), and FHNA modified oligonucleotides. Examination of
      crystal structures of a modified DNA heptamer duplex d(GCG)-T*-d(GCG):d(CGCACGC)
      by X-ray crystallography indicated that the cyclohexenyl ring system exhibits
      both the (3)H(2) and (2)H(3) conformations, similar to the C3'-endo/C2'-endo
      conformation equilibrium seen in natural furanose nucleosides. In the (2)H(3)
      conformation, the equatorial fluorine engages in a relatively close contact with
      C8 (2.94 A) of the 3'-adjacent dG nucleotide that may represent a pseudo hydrogen
      bond. In contrast, the cyclohexenyl ring of F-CeNA was found to exist exclusively
      in the (3)H(2) (C3'-endo like) conformation in the crystal structure of the
      modified A-form DNA decamer duplex [d(GCGTA)-T*-d(ACGC)](2.) In an animal
      experiment, a 16-mer F-CeNA gapmer ASO showed similar RNA affinity but
      significantly improved activity compared to that of a sequence matched MOE ASO,
      thus establishing F-CeNA as a useful modification for antisense applications.

PMID- 22591006
TI  - Constitutive activation of c-Abl/protein kinase C-delta/Fli1 pathway in dermal
      fibroblasts derived from patients with localized scleroderma.
AB  - BACKGROUND: A noncanonical pathway of transforming growth factor-beta signalling,
      the c-Abl/protein kinase C-delta (PKC-delta)/Friend leukemia virus integration 1
      (Fli1) axis, is a powerful regulator of collagen synthesis in dermal fibroblasts.
      OBJECTIVES: To investigate the significance of the c-Abl/PKC-delta/Fli1 pathway
      for the establishment of the profibrotic phenotype in lesional dermal fibroblasts
      from patients with localized scleroderma (LSc). METHODS: The activation status of
      the c-Abl/PKC-delta/Fli1 pathway was evaluated by immunoblotting and chromatin
      immunoprecipitation using cultured dermal fibroblasts from patients with LSc and
      closely matched healthy controls and by immunostaining on skin sections. The
      effects of a platelet-derived growth factor receptor inhibitor AG1296 and gene
      silencing of c-Abl on the expression levels of type I collagen were evaluated by
      immunoblotting. RESULTS: The phosphorylation levels of Fli1 at threonine 312 were
      increased, while the total Fli1 levels and the binding of Fli1 to the COL1A2
      promoter were decreased, in cultured LSc fibroblasts compared with cultured
      normal fibroblasts. Furthermore, in cultured LSc fibroblasts, the expression
      levels of c-Abl were elevated compared with cultured normal fibroblasts and PKC
      delta was preferentially localized in the nucleus. These findings were also
      confirmed in vivo by immunohistochemistry using skin sections. Moreover, gene
      silencing of c-Abl, but not AG1296, significantly suppressed the expression of
      type I collagen in cultured LSc fibroblasts. CONCLUSIONS: Constitutive activation
      of the c-Abl/PKC-delta/Fli1 pathway at least partially contributes to the
      establishment of the profibrotic phenotype in LSc dermal fibroblasts, which
      provides a novel molecular basis to explain the efficacy of imatinib against skin
      sclerosis in a certain subset of LSc.

PMID- 22591007
TI  - Complete quantitative online analysis of methanol electrooxidation products via
      electron impact and electrospray ionization mass spectrometry.
AB  - We report on a novel approach for complete quantitative online product analysis
      in electrocatalytic reactions, combining electron impact ionization mass
      spectrometry (EI-MS) and electrospray ionization mass spectrometry (ESI-MS) for
      simultaneous detection of both volatile and nonvolatile reaction products. The
      potential of this method is demonstrated using continuous methanol oxidation in a
      flow cell. The overall reaction rate was followed via the Faradaic current; CO(2)
      formation was monitored mass spectrometrically via a membrane inlet system, and
      formaldehyde and formic acid were detected by ESI-MS after a derivatization
      extraction-separation procedure introduced recently (Zhao, W.; Jusys, Z.; Behm,
      R. J. Anal. Chem.2010, 82, 2472-2479) providing quantitative data on the product
      distribution. In a more general sense, this approach is applicable for a wide
      range of reactions at the solid-liquid interface or in liquid phase.

PMID- 22591008
TI  - General and selective head-to-head dimerization of terminal alkynes proceeding
      via hydropalladation pathway.
AB  - A general highly regio- and stereoselective palladium-catalyzed head-to-head
      dimerization reaction of terminal acetylenes is presented. This methodology
      allows for the efficient synthesis of a variety of 1,4-enynes as single E
      stereoisomers. Computational studies reveal that this dimerization reaction
      proceeds via the hydropalladation pathway.

PMID- 22591009
TI  - Metal-mediated dihydrogen activation. What determines the transition-state
      geometry?
AB  - Density functional theory and absolutely localized molecular orbital energy
      decomposition analysis calculations were used to calculate and analyze dihydrogen
      activation transition states and reaction pathways. Analysis of a variety of
      transition-metal complexes with d(0), d(6), d(8), and d(10) orbital occupation
      with a diverse range of metal ligands reveals that for transition states, akin to
      dihydrogen sigma complexes, there is a continuum of activated H-H bond lengths
      that can be classified as "dihydrogen" (0.8-1.0 A), "stretched or elongated" (1.0
      1.2 A), and "compressed dihydride" (1.2-1.6 A). These calculations also
      quantitatively for the first time reveal that the extent to which H(2) is
      activated in the transition-structure geometry depends on back-bonding orbital
      interactions and not forward-bonding orbital interactions. This is true
      regardless of the mechanism or whether the metal ligand complex acts as an
      electrophile, ambiphile, or nucleophile toward dihydrogen.

PMID- 22591010
TI  - Non-synonymous SNPs in MC1R gene are associated with the extended black variant
      in domestic ducks (Anas platyrhynchos).
AB  - In this study, we performed a sequence characterization of the duck melanocortin
      1 receptor (alpha-melanocyte stimulating hormone receptor) (MC1R) gene to analyze
      the relationship between MC1R polymorphism and the extended black variant in
      domestic ducks based on the extended black (E) and non-extended black (e(+) )
      allele hypothesis of the duck MC1R gene. Both c.52G>A and c.376G>A substitutions
      are highly associated with the duck extended black variant (P < 0.01), but the
      novel c.52G>A substitution is more of a fit for the allele hypothesis of the duck
      MC1R gene.

PMID- 22591011
TI  - Tuning the electronic properties of semiconducting transition metal
      dichalcogenides by applying mechanical strains.
AB  - Semiconducting transition metal dichalcogenides (TMDs) are emerging as the
      potential alternatives to graphene. As in the case of graphene, the monolayer of
      TMDs can easily be exfoliated using mechanical or chemical methods, and their
      properties can also be tuned. At the same time, semiconducting TMDs (MX(2); M =
      Mo, W and X = S, Se, Te) possess an advantage over graphene in that they exhibit
      a band gap whose magnitude is appropriate for applications in the opto-electronic
      devices. Using ab initio simulations, we demonstrate that this band gap can be
      widely tuned by applying mechanical strains. While the electronic properties of
      graphene remain almost unaffected by tensile strains, we find TMDs to be
      sensitive to both tensile and shear strains. Moreover, compared to that of
      graphene, a much smaller amount of strain is required to vary the band gap of
      TMDs. Our results suggest that mechanical strains reduce the band gap of
      semiconducting TMDs causing an direct-to-indirect band gap and a semiconductor-to
      metal transition. These transitions, however, significantly depend on the type of
      applied strain and the type of chalcogenide atoms. The diffuse nature of heavier
      chalcogenides require relatively more tensile and less shear strain (when the
      monolayer is expanded in y-direction and compressed in x-direction) to attain a
      direct-to-indirect band gap transition. In addition, our results demonstrate that
      the homogeneous biaxial tensile strain of around 10% leads to semiconductor-to
      metal transition in all semiconducting TMDs, while through pure shear strain this
      transition can only be achieved by expanding and compressing the monolayer of
      MTe(2) in the y- and x-directions, respectively. Our results highlight the
      importance of tensile and pure shear strains in tuning the electronic properties
      of TMDs by illustrating a substantial impact of the strain on going from MS(2) to
      MSe(2) to MTe(2).

PMID- 22591012
TI  - Stability of the physical properties of plasticized edible films from squid
      (Todarodes pacificus) mantle muscle during storage.
AB  - Edible films from squid mantle muscle plasticized with different plasticizers
      were stored at 25  degrees C, 50% RH before the determination of physical
      properties. The results showed that tensile strength significantly increased (P <
      0.05) upon the storage time, especially for the film plasticized with glucose,
      while there was no significant change (P >= 0.05) in elongation at break of all
      plasticized films. Water vapor permeability of glucose-plasticized film
      significantly decreased (P < 0.05) during storage, while there was only a slight
      change in those with glycerol, sorbitol, and fructose. Redness and yellowness of
      the films became significantly higher (P < 0.05) during storage, especially for
      the films plasticized with fructose and glucose. SDS-PAGE and protein solubility
      in SDS solution showed a possibility of protein aggregation throughout the
      storage. From these results, it is suggested that the changes in physical
      properties of the films were caused by the progress of Maillard reaction.
      PRACTICAL APPLICATION: In this study, squid mantle muscle was used as an edible
      film-forming material. By mixing with Na-citrate, squid mantle muscle possessed
      the ability to form transparent films with an excellent UV barrier property.
      Glycerol was found to be the most effective and stable plasticizer for the films.
      Edible films represent an option for the utilization of discarded squid during
      the fishing process.

PMID- 22591013
TI  - Overexpression of G protein-coupled receptor 5D in the bone marrow is associated
      with poor prognosis in patients with multiple myeloma.
AB  - BACKGROUND: G protein-coupled receptor 5D (GPRC5D) is a novel surface receptor.
      As this new subtype of G protein-coupled receptors was discovered, little is
      known about the role of this gene. MATERIALS AND METHODS: In this retrospective
      study, we investigated GPRC5D mRNA expression by real-time polymerase chain
      reaction (RT-PCR) in bone marrow (BM) of 48 patients with multiple myeloma (MM).
      RESULTS: Highly variable levels of GPRC5D (median, 288; quartiles, 17-928) were
      detected in patients with MM, whereas only low expression was detected in normal
      tissues (median, 1; quartiles, 1-23). High mRNA expression of GPRC5D correlated
      positively with high plasma cell count in bone marrow (r = 0.64, P < 0.001), high
      beta(2) -microglobulin (r = 0.42, P = 0.003) and poor-risk cytogenetics: deletion
      13q14 (rb-1), P = 0.003; and 14q32 translocation t(4;14)(p16;q32), P = 0.029.
      GPRC5D mRNA expression showed a significant correlation with overall survival (P
      = 0.031). The estimated overall survival of patients expressing GPRC5D above or
      below the median of 288 was 43.9% vs. 70.2% at 48 months. Here, we report, for
      the first time, the association of GPRC5D expression and cancer. CONCLUSIONS:
      Overexpression in poor-risk myeloma, low expression in normal tissues and cell
      surface expression identify GPRC5D as a potential novel cancer antigen. Our data
      demonstrate that GPRC5D is a prognostic factor in MM correlating with other major
      risk factors.

PMID- 22591014
TI  - Functional associations of genetic variants involved in the clinical
      manifestation of erythropoietic protoporphyria in the Argentinean population.
AB  - BACKGROUND: Combined inheritance of genetic variants in ferrochelatase gene
      (FECH) are implicated in clinical manifestation of Erythropoietic Protoporphyria
      (EPP). OBJECTIVE: Identify the genetic variants in FECH gene and their
      associations in the expression of EPP in Argentina. Determine the allelic
      frequency of polymorphic variants, associations in cis and its linkage
      disequilibrium. METHODS: The FECH gene was PCR-amplified and sequenced. Allelic
      variants of intragenic polymorphisms were identified by PCR followed by
      sequencing or restriction digestion analysis. Residual FECH activity was
      determined by prokaryotic expression in Escherichia coli JM109. Data were
      analyzed using Haploview and Statistix 9. RESULTS: Ten mutations were identified:
      three novel (p.S222N; p.R298X and p.R367X) and seven already known
      (g.12490_18067del; p.R115X; p.I186T; c.580_584delTACAG; c.598 + 1 G>T; p.Y209X
      and p.W310X). The p.R115X mutation was found in two families. The p.S222N
      mutation expressed 5% of normal activity. Only individuals who inherited a
      mutation combined in trans to a low expression allele c.1-251G, c.68-23T, and
      c.315-48C, showed clinical symptoms. The absence of c.315-48C variant was
      sufficient for not triggering EPP. However, these variants showed high levels of
      cosegregation and GTC haplotype is over-represented in EPP patients. CONCLUSION:
      In the dominant inheritance form of EPP, c.315-48C variant in trans to the
      mutated allele is sufficient to trigger the disease. The presence of GTC
      haplotype in all patients with dominant EPP could be due to the high level of
      cosegregation of c.315-48C with c.1-251G and c.68-23T variants in our population.

PMID- 22591015
TI  - Optimizing electrode-attached redox-peptide systems for kinetic characterization
      of protease action on immobilized substrates. Observation of dissimilar behavior
      of trypsin and thrombin enzymes.
AB  - In this work, we experimentally address the issue of optimizing gold electrode
      attached ferrocene (Fc)-peptide systems for kinetic measurements of protease
      action. Considering human alpha-thrombin and bovine trypsin as proteases of
      interest, we show that the recurring problem of incomplete cleavage of the
      peptide layer by these enzymes can be solved by using ultraflat template-stripped
      gold, instead of polished polycrystalline gold, as the Fc-peptide bearing
      electrode material. We describe how these fragile surfaces can be mounted in a
      rotating disk configuration so that enzyme mass transfer no longer limits the
      overall measured cleavage kinetics. Finally, we demonstrate that, once the system
      has been optimized, in situ real-time cyclic voltammetry monitoring of the
      protease action can yield high-quality kinetic data, showing no sign of
      interfering effects. The cleavage progress curves then closely match the
      Langmuirian variation expected for a kinetically controlled surface process.
      Global fit of the progress curves yield accurate values of the peptide cleavage
      rate for both trypsin and thrombin. It is shown that, whereas trypsin action on
      the surface-attached peptide closely follows Michaelis-Menten kinetics, thrombin
      displays a specific and unexpected behavior characterized by a nearly enzyme
      concentration-independent cleavage rate in the subnanomolar enzyme concentration
      range. The reason for this behavior has still to be clarified, but its occurrence
      may limit the sensitivity of thrombin sensors based on Fc-peptide layers.

PMID- 22591016
TI  - Handling the data management needs of high-throughput sequencing data: SpeedGene,
      a compression algorithm for the efficient storage of genetic data.
AB  - BACKGROUND: As Next-Generation Sequencing data becomes available, existing
      hardware environments do not provide sufficient storage space and computational
      power to store and process the data due to their enormous size. This is and will
      be a frequent problem that is encountered everyday by researchers who are working
      on genetic data. There are some options available for compressing and storing
      such data, such as general-purpose compression software, PBAT/PLINK binary
      format, etc. However, these currently available methods either do not offer
      sufficient compression rates, or require a great amount of CPU time for
      decompression and loading every time the data is accessed. RESULTS: Here, we
      propose a novel and simple algorithm for storing such sequencing data. We show
      that, the compression factor of the algorithm ranges from 16 to several hundreds,
      which potentially allows SNP data of hundreds of Gigabytes to be stored in
      hundreds of Megabytes. We provide a C++ implementation of the algorithm, which
      supports direct loading and parallel loading of the compressed format without
      requiring extra time for decompression. By applying the algorithm to simulated
      and real datasets, we show that the algorithm gives greater compression rate than
      the commonly used compression methods, and the data-loading process takes less
      time. Also, The C++ library provides direct-data-retrieving functions, which
      allows the compressed information to be easily accessed by other C++ programs.
      CONCLUSIONS: The SpeedGene algorithm enables the storage and the analysis of next
      generation sequencing data in current hardware environment, making system
      upgrades unnecessary.

PMID- 22591017
TI  - A new species of Choleoeimeria (Apicomplexa: Eimeriidae) from Meller's chameleon,
      Trioceros melleri (Sauria: Chamaeleonidae).
AB  - A captive specimen of Meller's chameleon, Trioceros melleri (Gray), originally
      from Tanzania and housed at the Oklahoma City Zoological Park Herpetarium,
      Oklahoma County, Oklahoma, was found to be passing an undescribed species of
      Choleoeimeria in its feces. Oocysts of Choleoeimeria steveuptoni n. sp. were
      cylindroidal, 38.5 * 17.8 (36-42 * 17-19) um with a bilayered wall and a shape
      index (length/width) of 2.2. A micropyle and oocyst residuum were absent, but a
      fragmented polar granule was often present. Ovoidal sporocysts were composed of 2
      valves joined by a suture and measured 11.3 * 9.1 (11-12 * 9-10) um; shape index
      of 1.3. Stieda, sub-Stieda, and para-Stieda bodies were absent. The sporocyst
      residuum consists of multiple globules dispersed along the perimeter of the
      sporocyst and between sporozoites. Sporozoites were elongate, 13.1 * 2.9 (12-15 *
      2.6-3.2) um with an elongate posterior refractile body. The new species
      represents the second coccidian documented from this lizard.

PMID- 22591018
TI  - SS-Stabilizing Proteins Rationally: Intrinsic Disorder-Based Design of
      Stabilizing Disulphide Bridges in GFP.
AB  - Abstract   The most attractive and methodologically convenient way to enhance
      protein stability is via the introduction of disulphide bond(s). However, the
      effect of the artificially introduced SS-bond on protein stability is often quite
      unpredictable. This raises the question of how to choose the protein sites in an
      intelligent manner, so that the 'fastening' of these sites by the SS-bond(s)
      would provide maximal protein stability. We hypothesize that the successful
      design of a stabilizing SS-bond requires finding highly mobile protein regions.
      Using GFP as an illustrative example, we demonstrate that the knowledge of the
      peculiarities of the intramolecular hydrophobic interactions, combined with the
      understanding of the local intrinsic disorder propensities (that can be evaluated
      by various disorder predictors, e.g., PONDRFIT), is sufficient to find the
      candidate sites for the introduction of stabilizing SS-bridge(s). In fact, our
      analysis revealed that the insertion of the engineered SS-bridge between two
      highly flexible regions of GFP noticeably increased the conformational stability
      of this protein toward the thermal and chemical unfolding. Therefore, our study
      represents a novel approach for the rational design of stabilizing disulphide
      bridges in proteins.

PMID- 22591019
TI  - Hrip1, a novel protein elicitor from necrotrophic fungus, Alternaria tenuissima,
      elicits cell death, expression of defence-related genes and systemic acquired
      resistance in tobacco.
AB  - Here, we report the identification, purification, characterization and gene
      cloning of a novel hypersensitive response inducing protein secreted by
      necrotrophic fungus, Alternaria tenuissima, designated as hypersensitive response
      inducing protein 1 (Hrip1). The protein caused the formation of necrotic lesions
      that mimic a typical hypersensitive response and apoptosis-related events
      including DNA laddering. The protein-encoding gene was cloned by rapid
      amplification of cDNA ends (RACE) method. The sequence analysis revealed that the
      cDNA is 495 bp in length and the open reading frame (ORF) encodes for a
      polypeptide of 163 amino acids with theoretical pI of 5.50 and molecular weight
      of 17 562.5 Da. Hrip1 induced calcium influx, medium alkalinization, activation
      of salicylic acid-induced protein kinase and several defence-related genes after
      infiltration in tobacco leaves. Cellular damage, restricted to the infiltrated
      zone, occurred only several hours later, at a time when expression of defence
      related genes was activated. After several days, systemic acquired resistance was
      also induced. The tobacco plant cells that perceived the Hrip1 generated a
      cascade of signals acting at local, short, and long distances, and caused the
      coordinated expression of specific defence responses in a way similar to
      hypersensitivity to tobacco mosaic virus. Thus, Hrip1 represents a powerful tool
      to investigate further the signals and their transduction pathways involved in
      induced disease resistance in necrotrophic fungi.

PMID- 22591020
TI  - Comparison of the prognostic value of the 6th and 7th editions of the Union for
      International Cancer Control TNM staging system in patients with lower esophageal
      cancer undergoing neoadjuvant chemotherapy followed by surgery.
AB  - Carcinoma of the esophagus is classified according to the Union for International
      Cancer Control (UICC) TNM staging system. The 7th edition of the UICC TNM staging
      system was published in 2009. This is the first study to compare the prognostic
      value of the TNM 6th and 7th editions in patients with esophageal carcinoma
      treated with chemotherapy followed by surgery. Two hundred forty-three patients
      with esophageal carcinoma were retrospectively selected from two referral
      centers. All patients received chemotherapy before surgery. Histopathologic data
      from the resection specimens were retrieved and restaged according to the TNM 7th
      edition. Disease-specific survival curves were plotted for depth of tumor
      invasion (ypT), lymph node status (ypN), and ypTNM stage and then compared.
      Median follow-up after surgery was 2.5 years (range 0.2-9 years). Survival
      analysis using the log-rank method revealed that there was a significant
      difference in survival between ypT4 disease and ypT3 disease (P= 0.003), but no
      difference between ypT0, ypT1, ypT2, and ypT3 categories irrespective of TNM
      edition used. Survival probability was significantly different between ypN0 and
      ypN1 (P= 0.001 for TNM 6th and 7th edition), as well as ypN2 and ypN3 (TNM 7th
      edition, P= 0.004), but not between ypN1 and ypN2 (TNM 7th edition, P= 0.89).
      Neither the TNM 6th nor 7th edition T staging provides accurate survival
      probability stratification. However, the advantage of the 7th edition is the
      introduction of a third tier in survival stratification for patients with nodal
      involvement.

PMID- 22591021
TI  - Effect of amiloride and spironolactone on renal tubular function, ambulatory
      blood pressure, and pulse wave velocity in healthy participants in a double
      blinded, randomized, placebo-controlled, crossover trial.
AB  - We wanted to test the hypothesis that treatment with amiloride or spironolactone
      reduced ambulatory (ABP) and central blood pressure (CBP) and that tubular
      transport via ENaCgamma and AQP2 was increased after furosemide treatment. During
      baseline conditions, there were no differences in ABP, CBP, renal tubular
      function, or plasma concentrations of vasoactive hormones. After furosemide
      treatment, an increase in CBP, CH(2)o, FE(Na), FE(K), u-AQP2/min, u
      ENaCgamma/min, PRC, p-Ang II, and p-Aldo was observed. The increases in water and
      sodium absorption via AQP2 and ENaC after furosemide treatment most likely are
      compensatory phenomena to antagonize water and sodium depletion.

PMID- 22591022
TI  - The response of marine picoplankton to ocean acidification.
AB  - Since industrialization global CO(2)  emissions have increased, and as a
      consequence oceanic pH is predicted to drop by 0.3-0.4 units before the end of
      the century - a process coined 'ocean acidification'. Consequently, there is
      significant interest in how pH changes will affect the ocean's biota and integral
      processes. We investigated marine picoplankton (0.2-2 um diameter) community
      response to predicted end of century CO(2)  concentrations, via a 'high-CO(2) '
      (~ 750 ppm) large-volume (11 000 l) contained seawater mesocosm approach. We
      found little evidence of changes occurring in bacterial abundance or community
      composition due to elevated CO(2)  under both phytoplankton pre-bloom/bloom and
      post-bloom conditions. In contrast, significant differences were observed between
      treatments for a number of key picoeukaryote community members. These data
      suggested a key outcome of ocean acidification is a more rapid exploitation of
      elevated CO(2)  levels by photosynthetic picoeukaryotes. Thus, our study
      indicates the need for a more thorough understanding of picoeukaryote-mediated
      carbon flow within ocean acidification experiments, both in relation to
      picoplankton carbon sources, sinks and transfer to higher trophic levels.

PMID- 22591023
TI  - High uterine contraction rates in births with normal and abnormal umbilical
      artery gases.
AB  - OBJECTIVE: To determine if the incidence of high contraction (HC) rates and
      associated decelerations were different in term births with metabolic acidemia
      (MA) compared to those with normal gases (N) over the last 4 h of labor. METHODS:
      MA included 316 babies with cord base deficits (BD) over 12 mmol/L N - 3,320
      babies with BD under 8 mmol/L. HC rates were defined as >5/10 min. RESULTS: One
      or more episodes of HC occurred in 43.7% of MA and 36.6% of N. (p = 0.015) In
      both groups the HC rates rose from about 1 in 30 patients at the beginning to 1
      in 7 to 9 patients at the end. MA showed a different transition of the
      deceleration response over time. At the beginning the average ratio of
      decelerations to uterine contractions was similar in both groups but over the
      final 140 min MA showed a consistently higher ratio. CONCLUSIONS: Although HC
      rates were more frequent in the MA, it was not uncommon in N. On average MA
      showed more decelerations at every level of contractions and had a persistently
      higher level of decelerations per contraction for more than 2 h before birth.

PMID- 22591024
TI  - Nutrition research in rural communities: application of ethical principles.
AB  - This narrative review focuses on ethics related to nutrition-specific community
      based research, within the framework of science for society, and focusing on the
      rights and well-being of fieldworkers and research participants. In addition to
      generally accepted conditions of scientific validity, such as adequate sample
      size, unbiased measurement outcome and suitable study population, research needs
      to be appropriate and feasible within the local context. Communities' suspicions
      about research can be overcome through community participation and clear
      dialogue. Recruitment of fieldworkers and research participants should be
      transparent and guided by project-specific selection criteria. Fieldworkers need
      to be adequately trained, their daily schedules and remuneration must be
      realistic, and their inputs to the study must be recognized. Fieldworkers may be
      negatively affected emotionally, financially and physically. Benefits to research
      participants may include physical and psychological benefits, minimal economic
      benefit, and health education; while risks may be of a physical, psychological,
      social, or economic nature. Targeting individuals in high-risk groups may result
      in social stigmatization. The time burden to the research participant can be
      minimized by careful attention to study procedures and questionnaire design.
      Potential benefits to the community, fieldworkers and research participants and
      anticipated knowledge to be gained should outweigh and justify the potential
      risks. Researchers should have an exit strategy for study participants. For
      effective dissemination of results to individual research participants, the host
      community and nutrition community, the language, format and level of presentation
      need to be appropriate for the target audience. 

PMID- 22591025
TI  - Which outcomes should we measure in vitiligo? Results of a systematic review and
      a survey among patients and clinicians on outcomes in vitiligo trials.
AB  - BACKGROUND: Relevant and reliable outcomes play a crucial role in the correct
      interpretation and comparison of the results of clinical trials. There is a lack
      of consensus around methods of assessment and outcome measures for vitiligo,
      which makes it difficult to compare results of randomized controlled trials
      (RCTs) and perform meta-analysis. OBJECTIVES: To describe the heterogeneity in
      outcome measures used in published RCTs of vitiligo treatments, and to report the
      most desirable outcomes from patients' and clinicians' perspectives. METHODS: We
      conducted a systematic review of outcome measures used in RCTs as well as a
      survey of the most desirable outcomes identified by patients and clinicians as
      part of a Vitiligo Priority Setting Partnership. RESULTS: Outcomes from 54
      eligible trials were analysed and compared with outcomes suggested by patients
      and clinicians. In the systematic review, 25 different outcomes were reported.
      Only 22% of trials had clearly stated primary outcome measures. Repigmentation
      was the most frequently reported outcome in 96% of trials and was measured using
      48 different scales. Only 9% of trials assessed quality of life. Thirteen per
      cent measured cessation of spreading of the disease and 17% of studies reported
      patients' opinions and satisfaction with the treatment. In contrast, out of 438
      suggestions made by patients and clinicians, cosmetically acceptable
      repigmentation (rather than percentage of repigmentation) was the most desirable
      outcome (68%), followed by cessation of spread of vitiligo (15%), quality of life
      (8%) and maintenance of repigmentation (4%). CONCLUSIONS: We propose that future
      vitiligo trials should include repigmentation, cosmetic acceptability of results,
      global assessment of the disease, quality of life, maintenance of repigmentation,
      stabilization of vitiligo and side-effects. International consensus among
      clinicians, researchers and patients is needed to establish an agreed core
      outcome set for future vitiligo trials.

PMID- 22591026
TI  - Examining ultramicroelectrodes for scanning electrochemical microscopy by white
      light vertical scanning interferometry and filling recessed tips by
      electrodeposition of gold.
AB  - In this paper, we present a technique to rapidly and directly examine
      ultramicroelectrodes (UMEs) by white light vertical scanning interferometry
      (VSI). This technique is especially useful in obtaining topographic information
      with nanometer resolution without destruction or modification of the UME and in
      recognizing tips where the metal is recessed below the insulating sheath. Two
      gold UMEs, one with a metal radius a = 25 MUm and relative insulating sheath
      radius RG = 2 and the other with a = 5 MUm and RG = ~1.5, were examined, and the
      average depth of the gold recessions was determined to be 1.15 MUm and 910 nm,
      respectively. Electrodeposition of gold was performed to fill the recessed hole,
      and the depth was reduced to ~200 nm. With the electrodeposited gold electrode
      and a conventional microelectrode (a = 25 MUm) as a tip and substrate,
      respectively, a tip/substrate distance, d, of 600 nm was achieved allowing
      scanning electrochemical microscopy (SECM) in positive feedback mode at a close
      distance, which is useful for measuring fast kinetics.

PMID- 22591027
TI  - Electron delocalization from the fullerene attachment to the diiron core within
      the active-site mimics of [FeFe]hydrogenase.
AB  - Attachment of the redox-active C(60)(H)PPh(2) group modulates the electronic
      structure of the Fe(2) core in [(MU-bdt)Fe(2)(CO)(5)(C(60)(H)PPh(2))]. The
      neutral complex is characterized by X-ray crystallography, IR, NMR spectroscopy,
      and cyclic voltammetry. When it is reduced by one electron, the spectroscopic and
      density functional theory results indicate that the Fe(2) core is partially spin
      populated. In the doubly reduced species, extensive electron communication occurs
      between the reduced fullerene unit and the Fe(2) centers as displayed in the spin
      density plot. The results suggest that the [4Fe4S] cluster within the H cluster
      provides an essential role in terms of the electronic factor.

PMID- 22591028
TI  - Cobalt-catalyzed vinylation of aromatic halides using beta-halostyrene:
      experimental and DFT studies.
AB  - A new protocol for the direct cobalt-catalyzed vinylation of aryl halides using
      beta-halostyrene has been developed in order to form functionalized stilbenes. A
      variety of aromatic halides featuring different reactive group were employed.
      This method proceeded smoothly with a total retention of the double bond
      configuration in the presence of triphenylphosphine as ligand. Preliminary DFT
      calculations rationalize these results and proposed a reaction pathway in
      agreement with the experimental conditions. This procedure offers a new route to
      the stereoselective synthesis of stilbenes.

PMID- 22591029
TI  - Eculizumab for the treatment of two recurrences of atypical hemolytic uremic
      syndrome in a kidney allograft.

PMID- 22591030
TI  - Literature search strategies for conducting knowledge-building and theory
      generating qualitative systematic reviews.
AB  - AIM: To report literature search strategies for the purpose of conducting
      knowledge-building and theory-generating qualitative systematic reviews.
      BACKGROUND: Qualitative systematic reviews lie on a continuum from knowledge
      building and theory-generating to aggregating and summarizing. Different types of
      literature searches are needed to optimally support these dissimilar reviews.
      DATA SOURCES: Articles published between 1989-Autumn 2011. These documents were
      identified using a hermeneutic approach and multiple literature search
      strategies. DISCUSSION: Redundancy is not the sole measure of validity when
      conducting knowledge-building and theory-generating systematic reviews. When
      conducting these types of reviews, literature searches should be consistent with
      the goal of fully explicating concepts and the interrelationships among them. To
      accomplish this objective, a 'berry picking' approach is recommended along with
      strategies for overcoming barriers to finding qualitative research reports.
      IMPLICATIONS: To enhance integrity of knowledge-building and theory-generating
      systematic reviews, reviewers are urged to make literature search processes as
      transparent as possible, despite their complexity. This includes fully explaining
      and rationalizing what databases were used and how they were searched. It also
      means describing how literature tracking was conducted and grey literature was
      searched. In the end, the decision to cease searching also needs to be fully
      explained and rationalized. CONCLUSION: Predetermined linear search strategies
      are unlikely to generate search results that are adequate for purposes of
      conducting knowledge-building and theory-generating qualitative systematic
      reviews. Instead, it is recommended that iterative search strategies take shape
      as reviews evolve.

PMID- 22591031
TI  - In vitro testing of zinc oxide sunscreens.
AB  - The UVA performances of two all-mineral zinc oxide sunscreens are measured
      following Colipa and ISO procedures and compared to a sunscreen containing only
      organic actives. It is found that the two sunscreen types yield very different in
      vitro SPF and UVA results. It shown that the results can be rationalized in terms
      of the differences in the monochromatic extinction spectra of the two types of
      sunscreens.

PMID- 22591032
TI  - Metabolic syndrome and all-cause mortality in older men and women.
AB  - BACKGROUND: Prevalence of metabolic syndrome (MetS) increases with age, but its
      association with all-cause mortality in older persons remains uncertain. This
      study investigated the association of all-cause mortality with MetS and its
      individual components in older men and women. METHODS: A total of 917 men and
      1043 women aged 65 years and older from two Italian population-based cohorts were
      included in the study. MetS was defined according to four different definitions:
      National Cholesterol Education Program (NCEP), NCEP revised according to the
      American Heart Association and National Heart Lung Blood Institute (NCEP-R),
      International Diabetes Organization (IDF) and Joint Interim Statement (JIS). All
      of these definitions include abdominal obesity, hyperglycaemia,
      hypertriglyceridaemia, low high-density lipoprotein cholesterol and hypertension.
      Hazard Ratios (HR) and their corresponding 95% confidence interval (95%CI)
      estimated from multivariable-adjusted Cox regression models were used to
      investigate the associations of all-cause mortality with baseline MetS status and
      individual MetS components. RESULTS: After 6.5 +/- 1.8 years of follow-up, there
      were 179 deaths among women and 193 among men. Mortality risk was increased in
      women with MetS by any definition, regardless of individual components, but
      limited to age 70-79 years (NCEP, HR = 2.02, 95%CI, 1.16-3.53; NCEP-R, HR = 2.51,
      95%CI, 1.45-4.34; IDF, HR = 2.16, 95%CI, 1.26-3.72; JIS, HR = 2.16, 95%CI, 1.26
      3.72). Mortality risk of men was associated with hypertriglyceridaemia below age
      70 years (HR = 2.50, 95%CI, 1.19-5.25), but unrelated to MetS status.
      CONCLUSIONS: Metabolic Syndrome is associated with all-cause mortality in older
      women but not in men. The association, however, is limited to a narrow age range.

PMID- 22591033
TI  - Belly dancer syndrome.

PMID- 22591034
TI  - Disulfide prodrugs of albitiazolium (T3/SAR97276): synthesis and biological
      activities.
AB  - We report herein the design, synthesis, and biological screening of a series of
      15 disulfide prodrugs as precursors of albitiazolium bromide (T3/SAR97276,
      compound 1), a choline analogue which is currently being evaluated in clinical
      trials (phase II) for severe malaria. The corresponding prodrugs are expected to
      revert back to the active bis-thiazolium salt through an enzymatic reduction of
      the disulfide bond. To enhance aqueous solubility of these prodrugs, an amino
      acid residue (valine or lysine) or a phosphate group was introduced on the
      thiazolium side chain. Most of the novel derivatives exhibited potent in vitro
      antimalarial activity against P. falciparum. After oral administration, the
      cyclic disulfide prodrug 8 showed the best improvement of oral efficacy in
      comparison to the parent drug.

PMID- 22591035
TI  - A novel pH-dependant and double crosslinked polymethacrylate-based polysphere
      matrix for enteric delivery of isoniazid.
AB  - This study aimed at developing double crosslinked isoniazid (INH)-loaded
      polymethyl-methacrylate-ethylcellulose (PMMA-EC) polyspheres for rate-controlled
      enteric drug delivery. A PMMA solution was manipulated with the addition of EC to
      produce polyspheres by drop-wise extrusion into a primary crosslinking solution
      of AlCl3 (25% w/v), before adding a second crosslinking solution of either 30%
      w/v BaCl2 (polysphere Batch A) or 30% w/v MgCl2 (polysphere Batch B). The
      polyspheres were then subjected to FTIR spectroscopic analysis, in vitro drug
      release studies, drug entrapment efficiency (DEE) determination as well as
      surface area and porositometric investigations. Molecular Mechanics (MM)
      simulations elucidated the interaction between the cations and the PMMA-EC
      combination. FTIR spectra revealed an affinity of PMMA for Ba(2+), Mg(2+) and
      Al(3+). SEM showed smooth robust polyspheres ranging between 4-6 mm.
      Porositometric analysis established that polysphere Batch A had larger pores
      (315.314 Aabs) than Batch B (234.603 Aabs). Drug release profiles from polysphere
      Batch A displayed burst release with 50% INH released within 2 h (N = 3) that was
      attributable to the larger ionic radius of the second crosslinker Ba(2+) compared
      Mg(2+) which was employed for polysphere Batch B. The latter produced polyspheres
      with superior control in INH release (<25% within 2 h) (N = 3) and a higher DEE
      with minimal pore formation. The experimental findings were well corroborated by
      the MM simulations. 

PMID- 22591036
TI  - Dialkyl phosphate-related ionic liquids as selective solvents for xylan.
AB  - Herein we describe a possibility of selective dissolution of xylan, the most
      important type of hemicellulose, from Eucalyptus globulus kraft pulp using ionic
      liquids (ILs). On the basis of the IL 1-butyl-3-methylimidazolium dimethyl
      phosphate, which is well-known to dissolve pulp, the phosphate anion was modified
      by substituting one oxygen atom for sulfur and selenium, respectively. This
      alteration reduces the hydrogen bond basicity of the IL and therefore prevents
      dissolution of cellulose fibers, whereas the less ordered xylan is still
      dissolved. (1)H NMR spectra of model solutions and Kamlet-Taft parameters were
      used to quantify the solvent polarity and hydrogen bond acceptor properties of
      the ILs. These parameters have been correlated to their ability to dissolve xylan
      and cellulose, which was monitored by (13)C NMR spectroscopy. It was found that
      the selectivity for xylan dissolution increases to a certain extent with
      decreasing hydrogen-bond-accepting ability of anions of the ILs.

PMID- 22591038
TI  - Intramolecular methylation of an allyl sulfone via lithium alkoxyaluminate;
      application to the enantioselective synthesis of the CD ring of vitamin D3.
AB  - Alcohol-directed intramolecular methylation of an enantiopure allyl sulfone using
      AlMe(3) provides a trans-hydrindane CD ring alcohol. The substrate cis-CD ring
      allyl sulfone alcohol is prepared via intramolecular allyl sulfonyl anion
      addition to aldehyde using Ba(OH)(2).

PMID- 22591037
TI  - Review article: current treatment options and management of functional dyspepsia.
AB  - BACKGROUND: Functional dyspepsia (FD), a common functional gastrointestinal
      disorder, is defined by the Rome III criteria as symptoms of epigastric pain or
      discomfort (prevalence in FD of 89-90%), postprandial fullness (75-88%), and
      early satiety (50-82%) within the last 3 months with symptom onset at least 6
      months earlier. Patients cannot have any evidence of structural disease to
      explain symptoms and predominant symptoms of gastroesophageal reflux are
      exclusionary. Symptoms of FD are non-specific and the pathophysiology is diverse,
      which explains in part why a universally effective treatment for FD remains
      elusive. AIM: To present current management options for the treatment of FD
      (therapeutic gain/response rate noted when available). RESULTS: The utility of
      Helicobacter pylori eradication for the treatment of FD is modest (6-14%
      therapeutic gain), while the therapeutic efficacy of proton pump inhibitors (PPI)
      (7-10% therapeutic gain), histamine-type-2-receptor antagonists (8-35%
      therapeutic gain), prokinetic agents (18-45%), tricyclic antidepressants (TCA)
      (response rates of 64-70%), serotonin reuptake inhibitors (no better than
      placebo) is limited and hampered by inadequate data. This review discusses
      dietary interventions and analyses studies involving complementary and
      alternative medications, and psychological therapies. CONCLUSIONS: A reasonable
      treatment approach based on current evidence is to initiate therapy with a daily
      PPI in H. pylori-negative FD patients. If symptoms persist, a therapeutic trial
      with a tricyclic antidepressant may be initiated. If symptoms continue, the
      clinician can possibly initiate therapy with an anti-nociceptive agent, a
      prokinetic agent, or some form of complementary and alternative medications,
      although evidence from prospective studies to support this approach is limited.

PMID- 22591040
TI  - Competitive role of CH4-CH4 and CH-pi interactions in C6H6-(CH4)n aggregates: the
      transition from dimer to cluster features.
AB  - The intermolecular methane-methane and benzene (Bz)-methane interactions
      formulated in this paper are suitable to investigate systems of increasing
      complexity. The proposed CH(4)-CH(4) and Bz-CH(4) potential energy functions are
      indeed applied to study some macroscopic properties of methane and important
      features of both small Bz-(CH(4))(n) (n > 1-10) clusters and Bz surrounded by
      several CH(4) molecules. Relevant parameters of the interaction, derived from
      molecular polarizability components, have been proved to be useful to describe in
      a consistent way both size repulsion and dispersion attraction forces. The
      proposed potential model also allows one to isolate the role of the different
      intermolecular energy contributions. The spatial distribution of the CH(4)
      molecules in the clusters is investigated by means of molecular dynamics
      simulations under various conditions, even when methane phase transition from
      liquid to gas is likely to occur. In addition, several properties, such as radial
      distribution functions, density values, and mean diffusion coefficients, are
      analyzed in detail.

PMID- 22591039
TI  - MELTING, a flexible platform to predict the melting temperatures of nucleic
      acids.
AB  - BACKGROUND: Computing accurate nucleic acid melting temperatures has become a
      crucial step for the efficiency and the optimisation of numerous molecular
      biology techniques such as in situ hybridization, PCR, antigene targeting, and
      microarrays. MELTING is a free open source software which computes the enthalpy,
      entropy and melting temperature of nucleic acids. MELTING 4.2 was able to handle
      several types of hybridization such as DNA/DNA, RNA/RNA, DNA/RNA and provided
      corrections to melting temperatures due to the presence of sodium. The program
      can use either an approximative approach or a more accurate Nearest-Neighbor
      approach. RESULTS: Two new versions of the MELTING software have been released.
      MELTING 4.3 is a direct update of version 4.2, integrating newly available
      thermodynamic parameters for inosine, a modified adenine base with an universal
      base capacity, and incorporates a correction for magnesium. MELTING 5 is a
      complete reimplementation which allows much greater flexibility and
      extensibility. It incorporates all the thermodynamic parameters and corrections
      provided in MELTING 4.x and introduces a large set of thermodynamic formulae and
      parameters, to facilitate the calculation of melting temperatures for perfectly
      matching sequences, mismatches, bulge loops, CNG repeats, dangling ends,
      inosines, locked nucleic acids, 2-hydroxyadenines and azobenzenes. It also
      includes temperature corrections for monovalent ions (sodium, potassium, Tris),
      magnesium ions and commonly used denaturing agents such as formamide and DMSO.
      CONCLUSIONS: MELTING is a useful and very flexible tool for predicting melting
      temperatures using approximative formulae or Nearest-Neighbor approaches, where
      one can select different sets of Nearest-Neighbor parameters, corrections and
      formulae. Both versions are freely available at
      http://sourceforge.net/projects/melting/and at http://www.ebi.ac.uk/compneur
      srv/melting/under the terms of the GPL license.

PMID- 22591041
TI  - Evaluation of Barrett's esophagus with CK7, CK20, p53, Ki67, and COX2 expressions
      using chromoendoscopical examination.
AB  - Barrett's esophagus (BE) is a complication of chronic gastroesophageal reflux
      disease and can be diagnosed when there is an endoscopically irregular Z-line and
      intestinal metaplasia (IM) in a biopsy obtained lower esophagus. It is still not
      clear whether IM in the gastric cardia or columnar mucosa without IM in the lower
      esophagus have any significance as BE, which is considered as preneoplastic. The
      aim of the study was to determine the immunohistochemical features of BE and
      columnar mucosa in the distal esophagus and also to evaluate the value of
      chromoendoscopy in the diagnosis of BE in a prospective manner. A total of 12
      chromoendoscopic biopsies (six from normal-looking unstained esophagus and six
      from esophageal mucosa stained with methyl blue suspicious of BE) were taken from
      111 cases who underwent endoscopy because of a variety of upper gastrointestinal
      symptoms. Immunohistochemical analysis was performed using CK7, CK20, p53, Ki67,
      and cyclooxygenase 2 (COX2). Of the 111 cases, 19 cases with carcinoma (nine
      adeno, six squamous, four undifferentiated carcinomas) and 17 cases with normal
      squamous epithelium were excluded, while 75 cases showing columnar epithelium,
      including 46 (61.3%) with IM and 29 (38,7%) without IM, were further evaluated
      immunohistochemically. CK7 was observed in surface, crypt, and glandular
      epithelium, whereas CK20 was expressed in surface and superficial crypt
      epithelium. No significant difference was observed between the Barrett and non
      Barrett type of CK7/20 staining pattern (P > 0,05). Expression of p53 did not
      show any difference between BE and columnar mucosa without IM, whereas COX2
      expression was significantly increased in BE (P < 0.05) in comparison with
      columnar mucosa without IM. Ki67 expression was significiantly higher both in
      upper and lower crypts in BE (P < 0.05). The present study showed that a Barrett
      pattern does not seem to exist; however, the analysis of COX2 expression and the
      Ki67 proliferation fraction by immunohistochemistry can be used to separate BE
      from non-Barrett's metaplasia of the distal esophagus. In our point of view, the
      immunohistochemical detection of p53 expression in Barrett's metaplasia stage is
      useless as a marker for early detection of high-risk patients.

PMID- 22591045
TI  - Upcoming New Feature in the Journal of Biomolecular Structure & Dynamics.

PMID- 22591042
TI  - Commercially sterilized mussel meats (Mytilus chilensis): a study on process
      yield.
AB  - The processing steps most responsible for yield loss in the manufacture of canned
      mussel meats are the thermal treatments of precooking to remove meats from
      shells, and thermal processing (retorting) to render the final canned product
      commercially sterile for long-term shelf stability. The objective of this study
      was to investigate and evaluate the impact of different combinations of process
      variables on the ultimate drained weight in the final mussel product (Mytilu
      chilensis), while verifying that any differences found were statistically and
      economically significant. The process variables selected for this study were
      precooking time, brine salt concentration, and retort temperature. Results
      indicated 2 combinations of process variables producing the widest difference in
      final drained weight, designated best combination and worst combination with 35%
      and 29% yield, respectively. Significance of this difference was determined by
      employing a Bootstrap methodology, which assumes an empirical distribution of
      statistical error. A difference of nearly 6 percentage points in total yield was
      found. This represents a 20% increase in annual sales from the same quantity of
      raw material, in addition to increase in yield, the conditions for the best
      process included a retort process time 65% shorter than that for the worst
      process, this difference in yield could have significant economic impact,
      important to the mussel canning industry.

PMID- 22591047
TI  - The Rho kinase inhibitor azaindole-1 has long-acting vasodilator activity in the
      pulmonary vascular bed of the intact chest rat.
AB  - Responses to a selective azaindole-based Rho kinase (ROCK) inhibitor (azaindole
      1) were investigated in the rat. Intravenous injections of azaindole-1 (10-300
      ug/kg), produced small decreases in pulmonary arterial pressure and larger
      decreases in systemic arterial pressure without changing cardiac output.
      Responses to azaindole-1 were slow in onset and long in duration. When baseline
      pulmonary vascular tone was increased with U46619 or L-NAME, the decreases in
      pulmonary arterial pressure in response to the ROCK inhibitor were increased. The
      ROCK inhibitor attenuated the increase in pulmonary arterial pressure in response
      to ventilatory hypoxia. Azaindole-1 decreased pulmonary and systemic arterial
      pressures in rats with monocrotaline-induced pulmonary hypertension. These
      results show that azaindole-1 has significant vasodilator activity in the
      pulmonary and systemic vascular beds and that responses are larger, slower in
      onset, and longer in duration when compared with the prototypical agent fasudil.
      Azaindole-1 reversed hypoxic pulmonary vasoconstriction and decreased pulmonary
      and systemic arterial pressures in a similar manner in rats with monocrotaline
      induced pulmonary hypertension. These data suggest that ROCK is involved in
      regulating baseline tone in the pulmonary and systemic vascular beds, and that
      ROCK inhibition will promote vasodilation when tone is increased by diverse
      stimuli including treatment with monocrotaline.

PMID- 22591048
TI  - Improved ion mobility resolving power with increased buffer gas pressure.
AB  - Security and military applications of analytical techniques demand a small,
      rugged, reliable instrument that has traditionally been served well by
      atmospheric pressure ion mobility spectrometry (IMS) systems. Modern threats
      stipulate these instruments must reliably operate in increasingly complex
      environments. Previous work has demonstrated that increasing the pressure of an
      IMS drift tube has the potential to increase the resolving power of IMS, but
      operation at low temperatures resulted in a leveling of the measured resolving
      power as a function of pressure. By creating a novel aperture grid/Faraday plate
      design, a high-pressure IMS (HPIMS) system has been created that maintains a
      resolving power efficiency of 80% regardless of the pressure applied to the cell.
      This allows previously unattainable resolving powers to be achieved utilizing a
      small (10.7 cm) IMS cell. Using high pressure, a stand-alone IMS cell of 10.7 cm
      length has demonstrated a resolving power of 102 when operated at 2.5 atm. An
      increase in peak-to-peak resolution was also noted as pressure increased.
      Finally, the slope of the resulting inverse mobility/pressure curve for a single
      analyte has been shown to be proportional to the collision-cross-section of the
      analyte of interest, providing a novel method for the calculation of collision
      cross-section of target ions from the HPIMS data.

PMID- 22591049
TI  - Influence of sequential thiolate oxidation on a nitrile hydratase mimic probed by
      multiedge X-ray absorption spectroscopy.
AB  - Nitrile hydratases (NHases) are Fe(III)- and Co(III)-containing hydrolytic
      enzymes that convert nitriles into amides. The metal-center is contained within
      an N(2)S(3) coordination motif with two post-translationally modified cysteinates
      contained in a cis arrangement, which have been converted into a sulfinate (R
      SO(2)(-)) and a sulfenate (R-SO(-)) group. Herein, we utilize Ru L-edge and
      ligand (N-, S-, and P-) K-edge X-ray absorption spectroscopies to probe the
      influence that these modifications have on the electronic structure of a series
      of sequentially oxidized thiolate-coordinated Ru(II) complexes ((bmmp
      TASN)RuPPh(3), (bmmp-O(2)-TASN)RuPPh(3), and (bmmp-O(3)-TASN)RuPPh(3)). Included
      is the use of N K-edge spectroscopy, which was used for the first time to extract
      N-metal covalency parameters. We find that upon oxygenation of the bis-thiolate
      compound (bmmp-TASN)RuPPh(3) to the sulfenato species (bmmp-O(2)-TASN)RuPPh(3)
      and then to the mixed sulfenato/sulfinato speices (bmmp-O(3)-TASN)RuPPh(3) the
      complexes become progressively more ionic, and hence the Ru(II) center becomes a
      harder Lewis acid. These findings are reinforced by hybrid DFT calculations
      (B(38HF)P86) using a large quadruple-zeta basis set. The biological implications
      of these findings in relation to the NHase catalytic cycle are discussed in terms
      of the creation of a harder Lewis acid, which aids in nitrile hydrolysis.

PMID- 22591050
TI  - Physical activity levels and supportive care needs for physical activity among
      breast cancer survivors with different psychosocial profiles: a cluster
      analytical approach.
AB  - The transition from breast cancer patient to survivor is associated with many
      treatment-related and psychosocial factors, which can influence health behaviour
      and associated needs. First, this study aimed to identify clusters of treatment
      related and psychosocial factors among breast cancer survivors. Second, clusters'
      physical activity levels and care needs for physical activity were evaluated.
      Breast cancer survivors (n= 440; 52 +/- 8 years) (3 weeks to 6 months post
      treatment) completed self-reports on physical and psychological symptoms; illness
      representations; social support and coping; physical activity and care needs for
      physical activity. Analyses identified four clusters: (1) a low distress-active
      approach group; (2) a low distress-resigned approach group; (3) a high distress
      active approach group; and (4) a high distress-emotional approach group. Physical
      activity levels were higher in the low distress groups than in the high distress
      emotional approach group. However, women with low distress and an active approach
      reported equal care needs for physical activity than women with high distress and
      an emotional approach. These findings suggest that care needs for physical
      activity are unrelated to distress and actual physical activity levels. The
      results emphasise the importance of screening for needs and provide a framework
      supporting the referral of breast cancer survivors to tailored interventions.

PMID- 22591051
TI  - Crystal morphology modification by the addition of tailor-made stereocontrolled
      poly(N-isopropyl acrylamide).
AB  - The use of additives in crystallization of pharmaceuticals is known to influence
      the particulate properties critically affecting downstream processing and the
      final product performance. Desired functionality can be build into these
      materials, e.g. via optimized synthesis of a polymeric additive. One such
      additive is the thermosensitive polymer poly(N-isopropyl acrylamide) (PNIPAM).
      The use of PNIPAM as a crystallization additive provides a possibility to affect
      viscosity at separation temperatures and nucleation and growth rates at higher
      temperatures. In this study, novel PNIPAM derivatives consisting of both
      isotactic-rich and atactic blocks were used as additives in evaporative
      crystallization of a model compound, nitrofurantoin (NF). Special attention was
      paid to possible interactions between NF and PNIPAM and the aggregation state of
      PNIPAM as a function of temperature and solvent composition. Optical light
      microscopy and Raman and FTIR spectroscopy were used to investigate the structure
      of the NF crystals and possible interaction with PNIPAM. A drastic change in the
      growth mechanism of nitrofurantoin crystals as monohydrate form II (NFMH-II) was
      observed in the presence of PNIPAM; the morphology of crystals changed from
      needle to dendritic shape. Additionally, the amphiphilic nature of PNIPAM
      increased the solubility of nitrofurantoin in water. PNIPAMs with varying
      molecular weights and stereoregularities resulted in similar changes in the
      crystal habit of the drug regardless of whether the polymer was aggregated or
      not. However, with increased additive concentration slower nucleation and growth
      rates of the crystals were observed. Heating of the crystallization medium
      resulted in phase separation of the PNIPAM. The phase separation had an influence
      on the achieved crystal morphology resulting in fewer, visually larger and more
      irregular dendritic crystals. No proof of hydrogen bond formation between PNIPAM
      and NF was observed, and the suggested mechanism for the observed dendritic
      morphology is related to the steric hindrance phenomenon. PNIPAM can be used as a
      crystallization additive with an obvious effect on the growth of NF crystals. 

PMID- 22591052
TI  - Semantics of the transitive construction: prototype effects and developmental
      comparisons.
AB  - This paper investigates whether an abstract linguistic construction shows the
      kind of prototype effects characteristic of non-linguistic categories, in both
      adults and young children. Adapting the prototype-plus-distortion methodology of
      Franks and Bransford (1971), we found that whereas adults were lured toward false
      positive recognition of sentences with prototypical transitive semantics, young
      children showed no such effect. We examined two main implications of the results.
      First, it adds a novel data point to a growing body of research in cognitive
      linguistics and construction grammar that shows abstract linguistic categories
      can behave in similar ways to non-linguistic categories, for example, by showing
      graded membership of a category. Thus, the findings lend psychological validity
      to the existing cross-linguistic evidence for prototypical transitive semantics.
      Second, we discuss a possible explanation for the fact that prototypical
      sentences were processed differently in adults and children, namely, that
      children's transitive semantic network is not as interconnected or cognitively
      coherent as adults'.

PMID- 22591054
TI  - Does simultaneous bilingualism aggravate children's specific language problems?
AB  - AIM: There is little data on whether or not a bilingual upbringing may aggravate
      specific language problems in children. This study analysed whether there was an
      interaction of such problems and simultaneous bilingualism. METHODS: Participants
      were 5- to 7-year-old children with specific language problems (LANG group, N =
      56) or who were typically developing (CONTR group, N = 60). Seventy-three
      children were Swedish-Finnish bilingual and 43 were Swedish-speaking monolingual.
      Assessments (in Swedish) included tests of expressive language, comprehension,
      repetition and verbal memory. RESULTS: Per definition, the LANG group had lower
      scores than the CONTR group on all language tests. The bilingual group had lower
      scores than the monolingual group only on a test of body part naming.
      Importantly, the interaction of group (LANG or CONTR) and bilingualism was not
      significant on any of the language scores. CONCLUSIONS: Simultaneous bilingualism
      does not aggravate specific language problems but may result in a slower
      development of vocabulary both in children with and without specific language
      problems. Considering also advantages, a bilingual upbringing is an option also
      for children with specific language problems. In assessment, tests of vocabulary
      may be sensitive to bilingualism, instead tests assessing comprehension, syntax
      and nonword repetition may provide less biased methods.

PMID- 22591055
TI  - Biotransformation of manganese oxides by fungi: solubilization and production of
      manganese oxalate biominerals.
AB  - The ability of the soil fungi Aspergillus niger and Serpula himantioides to
      tolerate and solubilize manganese oxides, including a fungal-produced manganese
      oxide and birnessite, was investigated. Aspergillus niger and S. himantioides
      were capable of solubilizing all the insoluble oxides when incorporated into
      solid medium: MnO(2)  and Mn(2) O(3) , mycogenic manganese oxide (MnO(x) ) and
      birnessite [(Na(0.3) Ca(0.1) K(0.1) )(Mn(4+) ,Mn(3+) )(2) O(4) .1.5H(2) O].
      Manganese oxides were of low toxicity and A. niger and S. himantioides were able
      to grow on 0.5% (w/v) of all the test compounds, with accompanying acidification
      of the media. Precipitation of insoluble manganese and calcium oxalate occurred
      under colonies growing on agar amended with all the test manganese oxides after
      growth of A. niger and S. himantioides at 25 degrees C. The formation of
      manganese oxalate trihydrate was detected after growth of S. himantioides with
      birnessite which subsequently was transformed to manganese oxalate dihydrate. Our
      results represent a novel addition to our knowledge of the biogeochemical cycle
      of manganese, and the roles of fungi in effecting transformations of insoluble
      metal-containing compounds in the environment.

PMID- 22591057
TI  - Intracostal neuralgia as a previously undescribed symptom of Schnitzler's
      syndrome.

PMID- 22591058
TI  - Harmonizing general practice teachers' development across Europe.

PMID- 22591059
TI  - Patient adherence to prescribed medication instructions for dyspepsia: the
      DIAMOND-study.
AB  - BACKGROUND: Insight into patient adherence is needed to enable an effect
      evaluation of medication for dyspepsia. OBJECTIVES: Adherence was explored by
      investigating two adherence outcome measures (completeness and intake fidelity)
      using data from the DIAMOND-study. METHODS: The DIAMOND-study is a pragmatic RCT
      comparing a 'step-up' with a 'step-down' treatment strategy. In step 1
      participants (n =653) were instructed to use five pills/day for maximally 30
      days: an antacid 4dd plus a placebo 1dd ('step-up') or a proton pump inhibitor
      1dd plus a placebo 4dd ('step-down'). If the complaints persisted, step 2 was
      started (H(2)-receptor antagonist 2dd), and subsequently step 3 (five pills/day,
      placebo and verum vice versa from step 1). Completeness was assessed by pill
      counts, intake fidelity by patient questionnaires measuring the degree to which
      patients adhered to specific instructions concerning timing, frequency, dose and
      way of intake. RESULTS: In step 1, patients used on average 3.9 pills/day (78% of
      the prescribed doses), in step 2, 1.7 pills/day (85%) and in step 3, 3.6
      pills/day (72%). For the four times daily pills, half of the patients used less
      than 80% of the prescribed pills per day. This was one third of the patients for
      the twice daily pills and one quarter for the once daily pills. There were no
      completeness differences between active or placebo medication and no differences
      between the study arms. As regards intake fidelity, 70% of the patients made one
      or more errors in the medication intake. CONCLUSION: There is room for
      improvement in adherence rates for dyspepsia medication.

PMID- 22591060
TI  - Cancer prognosis by general practitioners.
AB  - BACKGROUND: General practitioners are probably asked regularly about the
      prognosis for patients with cancer. There is no readily available source of
      information on the accuracy of their estimates. OBJECTIVE: To discover studies
      that have reported general practitioners estimates of prognosis. METHODS: A
      search for studies of estimates of prognosis in terminal cancer by general
      practitioners. RESULTS: Three papers were discovered, reporting on 836 patients.
      In only a quarter of patients was prognosis accurately estimated by general
      practitioners, even within broad limits. Hospital doctors and nurses performed
      similarly. We suggest considerable scope for further studies in general practice,
      which should not require sophisticated procedures. CONCLUSION: Evidence of GP's
      limited performance in cancer prognostication should push us to do better.

PMID- 22591061
TI  - EGPRN: European General Practice Research Network.

PMID- 22591064
TI  - Synthetic biotinylated peptide compound, BP21, specifically recognizes
      lysophosphatidylcholine micelles.
AB  - Lysophosphatidylcholine, a major phospholipid component of oxidized low-density
      lipoprotein, is implicated in many inflammatory diseases, including
      atherosclerosis. We previously reported that Asp-hemolysin-related synthetic
      peptide (P21) composed of 21 amino acid residues markedly inhibits the
      bioactivities of oxidized low-density lipoprotein and lysophosphatidylcholine, by
      directly binding to oxidized low-density lipoprotein and lysophosphatidylcholine.
      Here, to clarify whether P21 specifically binds to lysophosphatidylcholine and
      what forms of lysophosphatidylcholine with which P21 interact, we investigated
      the interaction between P21 containing two tryptophan residues and
      lysophosphatidylcholine by using fluorescence spectroscopy, polyacrylamide gel
      electrophoresis, and surface plasmon resonance. From tryptophan fluorescence
      measurements, N-terminally biotinylated P21 specifically interacted with
      lysophosphatidylcholine, at concentrations exceeding the critical micelle
      concentration. From tryptophan fluorescence quenching, the tryptophan residues in
      biotinylated P21 in the presence of lysophosphatidylcholine were mostly exposed
      on the outer side of the peptide. From polyacrylamide gel electrophoresis and
      surface plasmon resonance, bound to 1-palmitoyl-lysophosphatidylcholine at
      concentrations higher than 100 MUm, ensuring stable micelles. These results
      indicate that biotinylated P21 specifically recognizes lysophosphatidylcholine
      micelles. Further study of the interaction between biotinylated P21 and
      lysophosphatidylcholine micelles may provide important information for the
      prevention and treatment for many inflammatory diseases caused by
      lysophosphatidylcholine micelles.

PMID- 22591063
TI  - Synthesis and nicotinic receptor activity of chemical space analogues of N-(3R)-1
      azabicyclo[2.2.2]oct-3-yl-4-chlorobenzamide (PNU-282,987) and 1,4
      diazabicyclo[3.2.2]nonane-4-carboxylic acid 4-bromophenyl ester (SSR180711).
AB  - The Chemical Universe Generated Databases up to 11 atoms of CNOF (GDB-11) and up
      to 13 atoms of CNOClS (GDB-13) were used to enumerate analogues of the diamine
      part of two known alpha7 nicotinic receptor agonists and construct libraries of
      virtual analogues of these drugs. The libraries were scored using structure-based
      (docking to the nicotine binding site of the acetylcholine binding protein
      1uw6.pdb) or ligand-based (similarity to the parent drugs) methods, and the top
      scoring virtual ligands were inspected for easily accessible synthetic targets.
      In total, 21 diamines were prepared and acylated with aromatic carboxylic or
      oxycarbonic acids to produce 85 analogues of the parent drugs. The compounds were
      profiled by electrophysiology in Xenopus oocytes expressing human nicotinic
      acetylcholine receptor (nAChR) subtypes alpha7, alpha3beta2, alpha4beta2,
      alpha3beta4, or alpha4beta4. Characterization of selected compounds revealed
      eight inhibitors of the alpha7 nicotinic receptor and three positive allosteric
      modulators of the alpha3beta2 nAChR.

PMID- 22591065
TI  - Cost-effectiveness analysis of treatments for vertebral compression fractures.
AB  - BACKGROUND: Vertebral compression fractures (VCFs) can be treated by nonsurgical
      management or by minimally invasive surgical treatment including vertebroplasty
      and balloon kyphoplasty. OBJECTIVE: The purpose of the present study was to
      characterize the cost to Medicare for treating VCF-diagnosed patients by
      nonsurgical management, vertebroplasty, or kyphoplasty. We hypothesized that
      surgical treatments for VCFs using vertebroplasty or kyphoplasty would be a cost
      effective alternative to nonsurgical management for the Medicare patient
      population. METHODS: Cost per life-year gained for VCF patients in the US
      Medicare population was compared between operated (kyphoplasty and
      vertebroplasty) and non-operated patients and between kyphoplasty and
      vertebroplasty patients, all as a function of patient age and gender. Life
      expectancy was estimated using a parametric Weibull survival model (adjusted for
      comorbidities) for 858 978 VCF patients in the 100% Medicare dataset (2005-2008).
      Median payer costs were identified for each treatment group for up to 3 years
      following VCF diagnosis, based on 67 018 VCF patients in the 5% Medicare dataset
      (2005-2008). A discount rate of 3% was used for the base case in the cost
      effectiveness analysis, with 0% and 5% discount rates used in sensitivity
      analyses. RESULTS: After accounting for the differences in median costs and using
      a discount rate of 3%, the cost per life-year gained for kyphoplasty and
      vertebroplasty patients ranged from $US1863 to $US6687 and from $US2452 to $US13
      543, respectively, compared with non-operated patients. The cost per life-year
      gained for kyphoplasty compared with vertebroplasty ranged from -$US4878 (cost
      saving) to $US2763. CONCLUSIONS: Among patients for whom surgical treatment was
      indicated, kyphoplasty was found to be cost effective, and perhaps even cost
      saving, compared with vertebroplasty. Even for the oldest patients (85 years of
      age and older), both interventions would be considered cost effective in terms of
      cost per life-year gained.

PMID- 22591067
TI  - Fluorescence and phosphorescence from higher excited states of organic molecules.

PMID- 22591068
TI  - Systematic review and pooled analysis assessing the association between elderly
      age and outcome following surgical resection of esophageal malignancy.
AB  - The incidence of esophageal malignancy continues to increase worldwide. At the
      same time, average life expectancy levels continue to climb, ensuring that more
      patients will present in their 70s, 80s, and 90s. The aim of this pooled analysis
      is to compare short- and long-term outcomes for elderly and younger patients
      undergoing esophagectomy for malignancy. Studies comparing the outcomes of
      esophagectomy for malignancy in elderly and young cohorts of patients were
      included. The minimum threshold age used to define the elderly cohort was 70
      years. Primary outcomes were in-hospital mortality, overall and cancer-related 5
      year survival. Secondary outcomes were the length of hospital stay, the incidence
      of anastomotic leak, conduit ischemia, cardiac and pulmonary complications, and
      the use of neoadjuvant therapy. Twenty-five publications comprising 9531 and 2573
      operations on younger and elderly cohorts of patients respectively were analyzed.
      Elderly patients were less likely to receive neoadjuvant therapy (14.6% vs.
      29.47%; pooled odds ratio [POR]= 0.48; 95% confidence interval [C.I.]= 0.35-0.65;
      P < 0.05). Esophagectomy in elderly patients was associated with increased in
      hospital mortality (7.83% vs. 4.21%; POR = 1.87; 95% C.I. = 1.54-2.26; P < 0.05),
      as well as increased pulmonary (21.77% vs. 19.49%) and cardiac (18.7% vs. 13.17%)
      complications. Subset analysis of studies using an age threshold of 80 years
      showed an even more significant association between in-hospital mortality and
      elderly age (pooled odds ratio = 3.19; 95% C.I. = 1.6-6.35; P < 0.05). There were
      no significant differences between the groups in length of hospital stay,
      incidence of anastomotic leak, or conduit ischemia. The elderly group showed
      reduced overall 5-year survival (21.23% vs. 29.01%; pooled odds ratio = 0.73; 95%
      C.I. = 0.62-0.87; P < 0.05) and reduced cancer-free 5-year survival (34.4% vs.
      41.8%; POR = 0.75; 95% C.I. = 0.64-0.89; P < 0.05). Elderly patients are at
      increased risk of pulmonary and cardiac complications, and perioperative
      mortality following esophagectomy, and show reduced cancer-related 5-year
      survival compared with younger patients. These patients represent a high-risk
      cohort, who requires thorough assessment of medical comorbidity, targeted
      counseling, and optimized treatment pathways.

PMID- 22591066
TI  - MetaMapp: mapping and visualizing metabolomic data by integrating information
      from biochemical pathways and chemical and mass spectral similarity.
AB  - BACKGROUND: Exposure to environmental tobacco smoke (ETS) leads to higher rates
      of pulmonary diseases and infections in children. To study the biochemical
      changes that may precede lung diseases, metabolomic effects on fetal and maternal
      lungs and plasma from rats exposed to ETS were compared to filtered air control
      animals. Genome- reconstructed metabolic pathways may be used to map and
      interpret dysregulation in metabolic networks. However, mass spectrometry-based
      non-targeted metabolomics datasets often comprise many metabolites for which
      links to enzymatic reactions have not yet been reported. Hence, network
      visualizations that rely on current biochemical databases are incomplete and also
      fail to visualize novel, structurally unidentified metabolites. RESULTS: We
      present a novel approach to integrate biochemical pathway and chemical
      relationships to map all detected metabolites in network graphs (MetaMapp) using
      KEGG reactant pair database, Tanimoto chemical and NIST mass spectral similarity
      scores. In fetal and maternal lungs, and in maternal blood plasma from pregnant
      rats exposed to environmental tobacco smoke (ETS), 459 unique metabolites
      comprising 179 structurally identified compounds were detected by gas
      chromatography time of flight mass spectrometry (GC-TOF MS) and BinBase data
      processing. MetaMapp graphs in Cytoscape showed much clearer metabolic modularity
      and complete content visualization compared to conventional biochemical mapping
      approaches. Cytoscape visualization of differential statistics results using
      these graphs showed that overall, fetal lung metabolism was more impaired than
      lungs and blood metabolism in dams. Fetuses from ETS-exposed dams expressed lower
      lipid and nucleotide levels and higher amounts of energy metabolism intermediates
      than control animals, indicating lower biosynthetic rates of metabolites for cell
      division, structural proteins and lipids that are critical for in lung
      development. CONCLUSIONS: MetaMapp graphs efficiently visualizes mass
      spectrometry based metabolomics datasets as network graphs in Cytoscape, and
      highlights metabolic alterations that can be associated with higher rate of
      pulmonary diseases and infections in children prenatally exposed to ETS. The
      MetaMapp scripts can be accessed at http://metamapp.fiehnlab.ucdavis.edu.

PMID- 22591069
TI  - HIV risk among Australian men travelling overseas: networks and context matter.
AB  - Increasing international mobility presents a risk for communicable disease
      transmission. Overseas-acquired HIV infections have been increasingly observed
      across Australian jurisdictions. This includes a mix of men emigrating from
      countries with high HIV prevalence and men travelling abroad. There is currently
      little research exploring international mobility and HIV risk, and as a
      consequence the increase of men acquiring HIV while travelling overseas is poorly
      understood. This paper draws on data from a qualitative study exploring the risk
      perspectives and experiences of 14 Australian men who acquired HIV while
      travelling overseas in the years between 2000 and 2009. Participants articulated
      a strong desire to distance themselves from the identity of a tourist. Social
      networks were highlighted as important entry points to engage with other foreign
      travellers and expatriates. These networks were highly influential and were
      understood by the participants to provide guidance on how they should negotiate
      the local scene, including where to meet sex partners. Limited discussion of safe
      sex and HIV was mentioned in these contexts. The findings suggest that prevalent
      social norms and social networks play an influential role in how participants
      negotiate sex and social relations in overseas settings. These networks could
      potentially provide sites for effective HIV-prevention programmes.

PMID- 22591070
TI  - Insertion of functional groups into a Nd3+ metal-organic framework via single
      crystal-to-single-crystal coordinating solvent exchange.
AB  - Single-crystal-to-single-crystal (SCSC) transformations represent some of the
      most fascinating phenomena in chemistry. They are not only intriguing from a
      basic science point of view but also provide a means to modify or tune the
      properties of the materials via the postsynthetic introduction of suitable guest
      molecules or organic functional groups into their structures. Here, we describe
      UCY-2, a new flexible Nd(3+) metal-organic framework (MOF), which exhibits a
      unique capability to undergo a plethora of SCSC transformations with some of them
      being very uncommon. These structural alterations involve the replacement of
      coordinating solvent molecules of UCY-2 by terminally ligating solvents and
      organic ligands with multiple functional groups including -OH, -SH, -NH-, and 
      NH(2) or their combinations, chelating ligands, anions, and two different organic
      compounds. The SCSC coordinating solvent exchange is thus demonstrated as a
      powerful method for the functionalization of MOFs.

PMID- 22591071
TI  - Prognosis in primary effusion lymphoma is associated with the number of body
      cavities involved.
AB  - Primary effusion lymphoma (PEL) is a rare lymphoma associated with Kaposi sarcoma
      associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8), and
      characterized by a malignant body cavity effusion without solid organ or nodal
      involvement. Prognostic factors in patients with PEL have not been systematically
      studied. We conducted a literature search for patients with HHV8-positive PEL to
      identify potential prognostic factors for survival. Our search identified 147
      patients, among which 104 patients were HHV8-positive. The median overall
      survival was 9 months. The median age was 57 years with a male predominance
      (6:1). Pathologically, 33% of the patients expressed CD20 and 69% expressed CD30.
      Patients with PEL with > 1 body cavity involved had a median overall survival
      (OS) of 4 months compared with 18 months in patients with only one cavity
      involved (p = 0.003). Additionally, in patients with one involved body cavity,
      pericardial involvement was associated with a longer median OS than pleural
      followed by peritoneal involvement (40, 27 and 5 months, respectively; p = 0.04).
      In conclusion, our study suggests that the number and location of body cavities
      involved are prognostic in patients with PEL.

PMID- 22591072
TI  - Testing computational models of hyperpolarizability in a merocyanine dye using
      spectroscopic and DFT methods.
AB  - The structural and electronic properties of a highly solvatochromic merocyanine
      dye, 2-(3-cyano-5,5-dimethyl-4-(3-(1-octadecylpyridin-4(1H)-ylidene)prop-1
      enyl)furan-2(5H)-ylidene)malononitrile (pyr3pi), have been investigated using UV
      vis, NMR, hyper-Rayleigh scattering, and Raman spectroscopies and further
      interpreted using computational chemistry. Spectroscopic data indicate that
      pyr3pi exists in its zwitterionic form even in low polarity solvents with
      electronic absorption spectra showing a hypsochromic shift with an increase in
      solvent polarity and NMR experiments indicating an increasingly zwitterionic
      structure in chloroform as the temperature is lowered. Raman spectra in
      increasingly polar solvents show small variations of the structure that are
      consistent with a change toward a structure with more zwitterionic character.
      However, comparison of the calculated and experimental vibrational energies and
      intensities and comparison of NMR coupling constants with calculated bond order
      indicate that calculations underestimate the amount of charge separation seen in
      low polarity solvents. Although for this system density functional theory (DFT)
      calculations and the two-state model qualitatively reproduce negative
      solvatochromism, they fail to reproduce the trends in hyperpolarizability seen
      experimentally. This is attributed to solvent field DFT calculations
      underestimating the degree of charge separation in reaction fields representing
      low polarity solvents.

PMID- 22591073
TI  - Reconstruction of paternal genotypes over multiple breeding seasons reveals male
      green turtles do not breed annually.
AB  - For species of conservation concern, knowledge of key life-history and
      demographic components, such as the number and sex ratio of breeding adults, is
      essential for accurate assessments of population viability. Species with
      temperature-dependent sex determination can produce heavily biased primary sex
      ratios, and there is concern that adult sex ratios may be similarly skewed or
      will become so as a result of climate warming. Prediction and mitigation of such
      impacts are difficult when life-history information is lacking. In marine
      turtles, owing to the difficultly in observing males at sea, the breeding
      interval of males is unknown. It has been suggested that male breeding
      periodicity may be shorter than that of females, which could help to compensate
      for generally female-biased sex ratios. Here we outline how the use of molecular
      based paternity analysis has allowed us, for the first time, to assess the
      breeding interval of male marine turtles across multiple breeding seasons. In our
      study rookery of green turtles (Chelonia mydas), 97% of males were assigned
      offspring in only one breeding season within the 3-year study period, strongly
      suggesting that male breeding intervals are frequently longer than 1year at this
      site. Our results also reveal a sex ratio of breeding adults of at least 1.3
      males to each female. This study illustrates the utility of molecular-based
      parentage inference using reconstruction of parental genotypes as a method for
      monitoring the number and sex ratio of breeders in species where direct
      observations or capture are difficult.

PMID- 22591074
TI  - Bioresorbable polymer coated drug eluting stent: a model study.
AB  - In drug eluting stent technologies, an increased demand for better control,
      higher reliability, and enhanced performances of drug delivery systems emerged in
      the last years and thus offered the opportunity to introduce model-based
      approaches aimed to overcome the remarkable limits of trial-and-error methods. In
      this context a mathematical model was studied, based on detailed conservation
      equations and taking into account the main physical-chemical mechanisms involved
      in polymeric coating degradation, drug release, and restenosis inhibition. It
      allowed highlighting the interdependence between factors affecting each of these
      phenomena and, in particular, the influence of stent design parameters on drug
      antirestenotic efficacy. Therefore, the here-proposed model is aimed to simulate
      the diffusional release, for both in vitro and the in vivo conditions: results
      were verified against various literature data, confirming the reliability of the
      parameter estimation procedure. The hierarchical structure of this model also
      allows easily modifying the set of equations describing restenosis evolution to
      enhance model reliability and taking advantage of the deep understanding of
      physiological mechanisms governing the different stages of smooth muscle cell
      growth and proliferation. In addition, thanks to its simplicity and to the very
      low system requirements and central processing unit (CPU) time, our model allows
      obtaining immediate views of system behavior. 

PMID- 22591075
TI  - Causal systems categories: differences in novice and expert categorization of
      causal phenomena.
AB  - We investigated the understanding of causal systems categories--categories
      defined by common causal structure rather than by common domain content--among
      college students. We asked students who were either novices or experts in the
      physical sciences to sort descriptions of real-world phenomena that varied in
      their causal structure (e.g., negative feedback vs. causal chain) and in their
      content domain (e.g., economics vs. biology). Our hypothesis was that there would
      be a shift from domain-based sorting to causal sorting with increasing expertise
      in the relevant domains. This prediction was borne out: the novice groups sorted
      primarily by domain and the expert group sorted by causal category. These results
      suggest that science training facilitates insight about causal structures.

PMID- 22591076
TI  - Now is the right time to re-evaluate how we educate and regulate health care
      professionals.

PMID- 22591077
TI  - Globalisation in nursing: what does it mean for ICN and INR?

PMID- 22591078
TI  - Plagiarism: intention or not?

PMID- 22591080
TI  - Challenges on the path to cultural safety in nursing education.

PMID- 22591081
TI  - Nurses addressing access disparities in primary health care.

PMID- 22591085
TI  - Protecting patients, protecting healthcare workers: a review of the role of
      influenza vaccination.
AB  - AIM: Many health authorities recommend routine influenza vaccination for
      healthcare workers (HCWs), and during the 2009 A (H1N1) pandemic, the World
      Health Organization (WHO) recommended immunization of all HCWs worldwide. As this
      remains an important area of policy debate, this paper examines the case for
      vaccination, the role of local guidelines, barriers to immunization and
      initiatives to increase uptake. BACKGROUND: Seasonal influenza is a major threat
      to public health, causing up to 1 million deaths annually. Extensive evidence
      supports the vaccination of priority groups, including HCWs. Immunization
      protects HCWs themselves, and their vulnerable patients from nosocomial influenza
      infections. In addition, influenza can disrupt health services and impact
      healthcare organizations financially. Immunization can reduce staff absences,
      offer cost savings and provide economic benefits. METHODS: This paper reviews
      official immunization recommendations and HCW vaccination studies, including a
      recent International Federation of Pharmaceutical Manufacturers and Associations
      (IFPMA) survey of 26 countries from each region of the world. RESULTS: HCW
      immunization is widely recommended and supported by the WHO. In the IFPMA study,
      88% of countries recommended HCW vaccination, and 61% supported this financially
      (with no correlation to country development status). Overall, coverage can be
      improved, and research shows that uptake may be impacted by lack of conveniently
      available vaccines and misconceptions regarding vaccine safety/efficacy and
      influenza risk. CONCLUSIONS: Many countries recommend HCW vaccination against
      influenza. In recent years, there has been an increased uptake rate among HCWs in
      some countries, but not in others. Several initiatives can increase coverage,
      including education, easy access to free vaccines and the use of formal
      declination forms. The case for HCW vaccination is clear, and in an effort to
      further accelerate uptake as a patient safety measure, an increasing number of
      healthcare organizations, particularly in the USA, are implementing mandatory
      immunization policies, similar to other obligatory hygiene measures. However, it
      would be desirable if similar high vaccination uptake rates could be achieved
      through voluntary procedures.

PMID- 22591086
TI  - A review of the opportunities and challenges facing the nursing associations in
      Iran.
AB  - BACKGROUND: Nursing associations and organizations are deemed to be effective
      tools in promoting the profession. Professional nursing associations are an
      essential part of the nursing culture. Examining the challenges and opportunities
      confronting the associations would pave the way for the identification of their
      limitations and also would lead to more interactions among the members and the
      associations. METHODS: Following an extensive review of the literature and also
      examining the professional nursing associations in Iran, the common challenges
      facing the nursing associations are identified and their shared challenges with
      other associations in other countries have been explored. Lack of members and
      insufficient support from the associations, financial problems, non-professional
      activities of associations and lack of interactions among associations are among
      the important challenges that the nursing associations confront within Iran. The
      possibility for establishing specialized nursing associations for increasing
      teamwork activities can be pointed out as one of the available opportunities.
      CONCLUSION: Professional associations follow important priorities with regard to
      their objectives, which distinguishes each from the other. The clear introduction
      of objectives and pinpointing the convergences that might bring about clashes
      between them will lead to building confidence among nurses, and hopefully,
      increasing membership. Members' dynamic participation, and support and
      interactions between associations are among the measures for increasing the
      professional power. Researchers hope that this article could provide both nurses
      and professional associations with insights to support each other for the purpose
      of promoting professional development. Considering the insufficient research in
      the field, more studies are also suggested.

PMID- 22591087
TI  - Spanish nurses' credentialing in the 20th century.
AB  - BACKGROUND: Nurses credentialing as healthcare professionals commenced in Western
      Europe and in the USA by the end of the 19th and the beginning of the 20th
      century, boosted by the protestant reform movement. In Spain, it started in 1915,
      during the kingdom of Alfonso XIII (1902-1931). This historical period was marked
      by great political instability and big flaws in the healthcare delivery system.
      AIM: To describe the regulatory pathway that gave rise to the nursing profession
      in Spain, through official credentialing and regulation during the first third of
      the 20th century. METHOD: Documental, historical and regulatory documental
      research describing and analysing the national legislative sources used to
      regulate the professional development, as well as the education, training and
      competencies of the nursing practice in Spain, as compared with the developments
      in the European and American context. CONCLUSIONS: Professional development of
      the nursing profession in Western Europe and in the USA is consolidated during
      the 20th century as resulting in educational and training enhancement and the
      establishment of national and international professional bodies. In Spain, the
      regulatory and legal recognition of the nursing profession come into being in
      1915 in response to a request from a female religious congregation.

PMID- 22591088
TI  - Globalization, decision making and taboo in nursing.
AB  - This paper is a reflection on the representation of nurses and their practice at
      a global level. In considering the International Council of Nurses (ICN)
      conference in Malta (2011), it is clear that certain assumptions have been made
      about nurses and their practice which assume that globalization is under way for
      the whole of the profession and that the assumptions can be applied equally
      around the world. These assumptions appear in many ways to be implicit rather
      than explicit. The implicitness of the assumptions is examined against the
      particular decision-making processes adopted by the ICN. An attempt is then made
      to identify another base for the ongoing global work of the ICN. This involves
      the exploration of taboo (that which is forbidden because it is either holy or
      unclean) as a way of examining why nursing is not properly valued, despite years
      of international representation. The paper concludes with some thoughts on how
      such a new approach interfaces with the possibilities held out by new information
      technologies.

PMID- 22591089
TI  - Challenges on the path to cultural safety in nursing education.
AB  - AIM: The purpose of this study is to identify central challenges to be addressed
      in cultural safety education. BACKGROUND: In recent years, the idea of cultural
      safety has received increased attention as a way of dealing with diversity in the
      nursing profession, especially in divided societies. The idea of cultural safety
      goes beyond recognizing and appreciating difference, to an attempt to grappling
      with deeper issues like inequality, conflict and histories of oppression.
      METHODS: The paper is based on formative evaluation, using action research, of an
      academic nursing programme in Israel, involving Jewish and Arab students. Part of
      this research dealt with the integration of cultural safety education into the
      curriculum. FINDINGS: The study revealed four challenges in cultural safety
      education: making it safe for minorities to present their culture to the majority
      group ('the ambassador's dilemma'), dealing with tendency of groups to deny the
      existence of conflict ('the one big happy family fantasy'), making dynamics of
      oppression discussable ('the oppressed and the oppressor') and creating
      conditions in which people can freely choose their individual and group
      identities ('the threat of identity'). CONCLUSION: Cultural safety education may
      be experienced as unsafe for many participants. Better understanding of the
      challenges of cultural safety education is necessary for making it more
      effective.

PMID- 22591090
TI  - Bridging the theory practice gap: a review of Graduate Nurse Program (GNP) in
      Dubai, United Arab Emirates.
AB  - BACKGROUND: One of the prime concerns of government is the investment in people
      and resources for the education and health care of its nation. The United Arab
      Emirates has invested in improving Arab nurse education to reflect the latest
      emerging standards in international nurse education as part of this ongoing
      investment: a need to bridge the theory practice divide was identified.
      INTRODUCTION: The Dubai Health Authority (DHA), which is the main government
      healthcare provider in Dubai, granted full scholarship for Arab nationals to
      enrol in the first baccalaureate nursing degree program offered by a local
      university in the country. PROBLEM: Since its conception, 56 students have
      graduated from the program, of which eight graduates have resigned or did not
      join the nursing workforce. Current new graduates expressed lack of confidence
      and not feeling work ready to join the workforce; in addition, the nurses in
      service also voiced the opinion that the new Arab nursing graduates were
      inadequately prepared for service provision at the time of graduation.
      CONCLUSION: A graduate nurse program to bridge the gap between theory and
      practice and to ease the transition of new graduate nurses into the nursing
      workforce was developed by the DHA. DISCUSSION: This paper offers a positional
      discussion on the development of this program in Dubai, its findings, action
      planning and works in progress to resolve identified issues.

PMID- 22591091
TI  - Educational preparation for maternal, child and family health nurses in
      Australia.
AB  - AIM: The study aims to map and critique the current postgraduate educational
      nursing programmes offered to nurses and midwives in maternal, child and family
      health in Australia. BACKGROUND: Nursing specialties that focus on the early
      years of child health and development are based on international recognition of
      the developmental needs of the growing infant and of the social, health and
      economic consequences of failing to support families to raise their children in
      optimal environments. Little is known whether the educational programmes that
      prepare maternal, child and family health nurses (MCFHNs) for practice in
      Australia have kept up with new knowledge and understanding of the early years of
      life. METHODS: A survey of all maternal, child and family health education
      programmes offered in Australia was undertaken. FINDINGS: Marked variations in
      course titles, length, content, clinical exposure and award exist across the 12
      institutions offering such programmes in Australia. Many institutions provide
      inadequate preparation in some of the core skills required of the workforce.
      CONCLUSION: The establishment of minimum standards for the education of MCFHNs
      across Australia is required. This study also highlights the need for further
      research around the scope of practice of MCFHNs, and the role of midwives who are
      not nurses, in this specialty area.

PMID- 22591092
TI  - Midwifery students' perceived independence within the core competencies expected
      of the midwifery community upon graduation: an Italian study.
AB  - AIM: The general aim of this article is to describe the independence perceived by
      midwifery students who are due to qualify with regard to core competencies that
      are considered essential by the community of professional midwives working in
      Italian healthcare hospitals. METHODS: A multi-method research project was
      undertaken. One hundred sixty-seven midwives working in 11 regional facilities
      were approached with the aim of selecting the core competencies expected by
      graduands. In the same region, all graduands (24) educated at two universities
      were involved in the study aiming to discover the level of the independence (from
      0 none to 10 maximum) perceived in each core competence selected by the midwives.
      RESULTS: The average score obtained by graduands in the questionnaire containing
      102 core competencies was 717.4 (standard deviation 130.3, median 743). The
      minimum score was 363 and the highest was 916. Assuming the minimum cut-off at
      612 points, five students (20.8%) had a perceived level of independence below
      sufficiency. CONCLUSION: Italian midwifery education has been reformed five times
      since 1940. The reduction in the length of the direct entry midwifery programme
      as introduced in the latest Italian national reform, and the higher standard of
      education requested also by European Directives, cause an increasing number of
      students to prefer to extend their course duration and postpone graduation until
      they feel independent. Any change in curriculum should consider the impact in the
      short, medium and long terms. For this reason, each new policy should consider
      carefully the point of view of experts in the disciplines, such as midwifery,
      with the objective of protecting and developing their competence in taking care
      of women, newborns and their families.

PMID- 22591093
TI  - Saudi Arabian nurses' experiences of studying Masters degrees in Australia.
AB  - AIM: This paper presents findings from a study which explored a group of Saudi
      Arabian nurses' experiences of studying for a Masters degree in Australia.
      BACKGROUND: Arab states in the Middle East, Saudi Arabia in particular, have high
      expatriate nursing populations, and governments in the region have allocated
      considerable funding to up-skilling their health workforce, often at Western
      universities. However, there has been little research into the learning
      experiences of nursing students from Middle East nations. METHODS: A descriptive
      qualitative study design was used. Middle Eastern students undertaking Masters
      courses in a School of Nursing and Midwifery at one Australian university were
      invited to participate in a semi-structured interview. Ten Saudi students
      participated and data were analysed using content analysis. FINDINGS: Students
      experienced challenges related to the transition to very different forms of
      study; to managing relationships and family. They were resourceful, employing
      strategies to manage multiple demands, including differences in culture, and
      stressed the significance of strong personal relationships with staff. Students
      acknowledged being changed, even transformed, by their experience, and saw
      themselves as future change agents. CONCLUSION: Highly skilled local nursing
      professionals are being sought in many Middle Eastern countries and may undertake
      post-graduate studies in Western contexts quite different from their own.
      Students reported that, in spite of difficulties, their experience prompted
      transformational change: intellectually, psychologically and developmentally. It
      is necessary for staff to understand expectations and learning preferences of
      these students to ensure fruitful learning outcomes and benefits to nursing in
      their home countries.

PMID- 22591094
TI  - Jordanian perspectives on advanced nursing practice: an ethnography.
AB  - AIM: This study aimed to explore how different groups of participants perceived
      the concept of advanced nursing practice in Jordan. BACKGROUND: In Jordan, there
      are postgraduate educational programmes offering a Master's degree in clinical
      nursing for registered nurses. Intended to prepare nurses to practise at an
      advanced level as potential clinical nurse specialists in critical care,
      community health nursing and maternal newborn nursing, little was known prior to
      this study about the development of advanced nursing roles for nurses in Jordan
      and the drivers behind their establishment. METHODS: Using ethnographic design,
      narratives from semi-structured interviews and non-participant observation with
      participants from five Jordanian hospitals and two public universities were
      collected and analysed according to thematic analysis. FINDINGS AND DISCUSSION:
      Four themes emerged from the data: core competencies, specific practice area vs.
      generic practice, beneficiaries of advanced nursing practice and drivers for
      educational change. The findings are similar to those found in other countries
      and highlight the need for a consensual understanding between nurse
      educationalists, professional bodies and employers about what advanced nursing
      practice in Jordan should be, so that a common framework can be identified.
      CONCLUSION: Paralleling the lack of consistency in understanding of advanced
      nursing practice in the broader literature, participants described a number of
      different elements of advanced practice that are relevant to the specific context
      of contemporary Jordanian nursing.

PMID- 22591095
TI  - Approaches to nursing skills training in three countries.

PMID- 22591097
TI  - Characteristics of dog bites among nursing students and knowledge about their
      emergency management.
AB  - BACKGROUND: Dog bites represent a significant health concern leading to a variety
      of consequences. Nursing students should be appropriately educated in order to
      manage and help prevent such injuries. AIM: This paper is the first to report the
      lifetime experience and characteristics of dog bites among Greek nursing students
      and their knowledge in managing the above injuries. METHODS: A cross-sectional
      quantitative study was performed using an anonymous questionnaire distributed to
      first and fourth year nursing students from April though June 2009. A knowledge
      score based on key questions was set on a scale from 0 to 7, to assess their
      competence on bite injuries management. RESULTS: Of 237 nursing students
      recruited, 56 (23.6%) had experienced a dog bite. Men outnumbered women as dog
      bite victims [n = 15 (39.5%) vs. n = 41 (20.6%), P = 0.012]. Mean age at the
      attack was 11.1 (standard deviation = 5.6) years and legs sustained the majority
      of injuries (n = 31; 55.4%). Most bites (n = 39; 69.9%) involved a dog known to
      the victim, were provoked (n = 30; 53.6%) and occurred in a public place (n = 35;
      62.5%). Ten (17.9%) of the victims sustained a moderate or severe injury. The
      majority (67.9%) of students answered correctly to less than or equal to three
      out of seven key knowledge questions. After multiple linear regression analysis,
      previous educational course attendance was the only factor associated with
      increased score (b = 0.48, standard deviation = 0.17, 95% confidence interval =
      0.12-0.84, P = 0.009). CONCLUSIONS: Dog bites were common and presented
      characteristic patterns among nursing students, but knowledge in their management
      was suboptimal. Improved education should be provided during undergraduate
      studies.

PMID- 22591096
TI  - Racial disparities in job strain among American and immigrant long-term care
      workers.
AB  - BACKGROUND: Nursing homes are occupational settings, with an increasing minority
      and immigrant workforce where several psychosocial stressors intersect. AIM: This
      study aimed to examine racial/ethnic differences in job strain between Black (n =
      127) and White (n = 110) immigrant and American direct-care workers at nursing
      homes (total n = 237). METHODS: Cross-sectional study with data collected at four
      nursing homes in Massachusetts during 2006-2007. We contrasted Black and White
      workers within higher-skilled occupations such as registered nurses or licensed
      practical nurses (n = 82) and lower-skilled staff such as certified nursing
      assistants (CNAs, n = 155). RESULTS: Almost all Black workers (96%) were
      immigrants. After adjusting for demographic and occupational characteristics,
      Black employees were more likely to report job strain, compared with Whites
      [relative risk (RR): 2.9, 95% confidence interval (CI) 1.3 to 6.6]. Analyses
      stratified by occupation showed that Black CNAs were more likely to report job
      strain, compared with White CNAs (RR: 3.1, 95% CI: 1.0 to 9.4). Black workers
      were also more likely to report low control (RR: 2.1, 95% CI: 1.1 to 4.0).
      Additionally, Black workers earned $2.58 less per hour and worked 7.1 more hours
      per week on average, controlling for potential confounders. CONCLUSION: Black
      immigrant workers were 2.9 times more likely to report job strain than White
      workers, with greater differences among CNAs. These findings may reflect
      differential organizational or individual characteristics but also interpersonal
      or institutional racial/ethnic discrimination. Further research should consider
      the role of race/ethnicity in shaping patterns of occupational stress.

PMID- 22591098
TI  - A comparison of the factors influencing life satisfaction between Korean older
      people living with family and living alone.
AB  - BACKGROUND: As the global population of older people continuously increases, many
      countries are beginning to experience health problems associated with older age.
      These countries may be interested in knowing and understanding the health
      problems experienced by the older Korean population, which is projected to age
      the most rapidly. AIM: This study aimed to compare and examine the factors that
      influence the life satisfaction between older people living with their family and
      those living alone. METHODS: A cross-sectional survey was conducted. The
      participants comprised a total 300 older Koreans (150 living with their family,
      150 living alone) aged 65 years or over who met the eligibility criteria. All
      measures were self-administered. Data were analysed using the SAS statistical
      software program version 6.12 (SAS Institute Inc., Cary, NC). RESULTS: The older
      people living with their family were better than the older people living alone in
      perceived health status, self-esteem, depression and life satisfaction. Perceived
      health status, self-esteem, depression, age and monthly allowance were found to
      be the factors related to the life satisfaction of older people living with their
      family and those living alone. The factors that were found to have the greatest
      influence on the life satisfaction of older people living with their family and
      those living alone were depression and perceived health, respectively.
      CONCLUSIONS: This study may help healthcare providers to understand the factors
      that can influence the life satisfaction among older people living with their
      family and living alone in Korea.

PMID- 22591099
TI  - Translation and validation of two evidence-based nursing practice instruments.
AB  - BACKGROUND: Using existing instruments when assessing nurses' readiness for
      evidence-based practice facilitates comparison of research findings and adds to
      nursing knowledge in a global context. AIM: The study aims to: (1) translate the
      Information Literacy for Evidence Based Nursing Practice((c)) (ILNP((c)))
      questionnaire and the Evidence-based Practice Beliefs Scale((c)) (EBP Beliefs
      Scale((c))), (2) assess their appropriateness for use in Iceland, and 3) estimate
      the psychometric properties of the translated EBP Beliefs Scale [Icelandic-EBP
      Beliefs Scale (I-EBP Beliefs Scale)]. METHODS: The instruments were evaluated for
      appropriateness and relevancy before translation, and the ILNP((c)) was modified
      to fit the Icelandic context. Translation followed recommended approaches,
      including back-translation. Pilot testing of both instruments ensued. A random
      sample of 540 nurses answered and returned the questionnaires. Reliability and
      validity of the I-EBP Beliefs Scale were tested on 471 complete I-EBP Beliefs
      Scale. Data were collected in 2007. RESULTS: The translated instruments
      demonstrated clarity and conciseness; however, the ILNP((c)) needed to be further
      modified. For the I-EBP Beliefs Scale, Cronbach's alpha was 0.86 and Spearman
      Brown r was 0.87. Principal components analysis supported the I-EBP Beliefs
      Scale's construct validity and unidimensional structure. Criterion validity was
      established by known-groups comparison (t-tests and one-way analyses of
      variance). CONCLUSIONS: The ILNP((c)) and the EBP Beliefs Scale((c)) can be used
      in contexts other than those for which they were developed. The I-EBP Scale is a
      psychometrically sound instrument and its performance supports the validity of
      the original scale. The instruments can be used to gather valuable information
      about nurses' readiness for evidence-based practice.

PMID- 22591100
TI  - Transcultural adaptation of the filial responsibility interview schedule for
      Brazil.
AB  - BACKGROUND: In developed countries, filial responsibility in relation to caring
      for elderly parents has been systematically studied. In Brazil and other
      developing countries, however, it is a relatively new topic and has not yet been
      included in the research agenda on ageing. OBJECTIVE: To describe the process of
      cross-cultural adaptation of the qualitative phase of the filial responsibility
      interview schedule into Brazilian Portuguese. METHODS: An expert committee of six
      team members participated in the study. In addition, individual interviews were
      held with 11 caregivers of older persons to evaluate the quality of the final
      Portuguese version of the schedule. The process included examining conceptual,
      item, semantic and operational equivalencies. Conceptual and item equivalencies
      were based on a literature review and on discussions with the expert committee.
      Semantic equivalence was attained through translation, back-translation, expert
      committee evaluation and pre-testing. The final version was pre-tested in
      caregivers of older persons enrolled in the home care programme of a primary
      health care service in Southern Brazil. RESULTS: Conceptual, item, semantic and
      operational equivalencies were attained. Through the interviews, responses to the
      open-ended questions concerning filial responsibility in the care for elderly
      parents pertained to the following categories: possibility of
      institutionalization of elderly parents, caregiver expectations, difficulties in
      being a child caregiver and responsibility as a natural process. CONCLUSION: The
      Portuguese version presented good semantic equivalence and the results showed
      that the concepts and items are applicable to the Brazilian context.

PMID- 22591101
TI  - Turkish version of the Stroke-Specific Quality of Life Scale.
AB  - AIM: To test the reliability and validity of the Turkish version of the Stroke
      Specific Quality of Life Scale (SS-QOL). BACKGROUND: Stroke is a leading cause of
      activity limitation and participation restriction that negatively affect health
      related quality of life. The assessment of SS-QOL in stroke patients has not been
      validated in Turkey. METHODS: Cross-sectional and methodological research design
      was used. Five hundred stroke survivors who had been diagnosed with stroke at
      least 6 months previously were included in this cross-sectional study. The
      reliability of the SS-QOL was based on internal consistency, item correlation.
      Construct validity was evaluated by Exploratory Factor Analysis. Cronbach's alpha
      coefficient was calculated for the total score of the SS-QOL to establish the
      internal consistency of the instrument. Construct validity was assessed by
      comparing patients' scores on the SS-QOL with those obtained by other test
      methods: SF-36 Health Survey and Katz Index of Activities of Daily Living.
      FINDINGS: In the process of adaptation to the Turkish population, the scale was
      converted to 48 items. The correlation coefficient for the test-retest scores of
      the SS-QOL was calculated as 0.81. Internal consistency for the scale showed
      Cronbach's alpha = 0.97. As a result of applying factor analysis to the scale,
      eight factors were obtained, which accounted for 77.47% of the scale's total
      variance. CONCLUSION: SS-QOL is a reliable and valid instrument for measuring
      self-reported health-related quality of life at group level among people with
      stroke who are diagnosed with stroke at least 6 months previously in the Turkish
      population.

PMID- 22591102
TI  - Procedures for an instrument development study: the Botswana experience.
AB  - BACKGROUND: Health protective sexual communication (HPSC) between sexual partners
      can contribute to human immunodeficiency virus (HIV) prevention, but women face
      difficulties with HPSC because of cultural and gender issues. PURPOSE: To present
      the procedures for an instrument development study conducted in Botswana between
      2006 and 2008 on different aspects of HPSC. The study was guided by the theory of
      planned behaviour constructs. METHODS: A literature review and a qualitative
      pilot study among young women aged 18-35 years in Gaborone city clinics generated
      items for the measures. Eleven measures were developed and evaluated for content
      validity. The measures were translated and evaluated by three typical
      participants for cultural relevance and acceptance. A quantitative pilot among
      ten women and a larger quantitative study among 280 other young women followed in
      13 Gaborone city clinics for internal consistency reliability, and construct
      validity based on principal components analysis. All women who met selection
      criteria consented and responded to all questions. Research protocols were
      strictly adhered to. RESULTS: Eight measures were reliable, with Cronbach's
      alphas between 0.69 and 0.95. Underlying factors were extracted for these. Two
      measures were unreliable, one with spuriously low reliability due to its brevity.
      Some significant relationships were identified between measures. DISCUSSION OF
      FINDINGS: The results highlighted the importance of HPSC, the significant
      influence of the male sexual partners and other relatives, and the need to
      integrate HPSC at all levels of HIV/acquired immunodeficiency syndrome prevention
      and research, focusing on the effectiveness of HPSC.

PMID- 22591103
TI  - Effectiveness of combined pulsed dye and Q-switched ruby laser treatment for
      large to giant congenital melanocytic naevi.
AB  - BACKGROUND: There is no consensus on the most appropriate treatment for patients
      with large to giant congenital melanocytic naevi (CMN) because of the risk of
      melanoma development. Surgical excision followed by skin grafting or expanded
      skin coverage may cause unfavourable scarring. There is a balance to be achieved
      between minimizing the disfiguring appearance and the risk of malignant change.
      The pulsed dye laser (PDL) is commonly used for vascular lesions and is highly
      absorbed by melanin and haemoglobin. Its pulse duration is longer than that of Q
      switched ruby lasers (QsRL), which can have nonspecific photothermolytic effects
      on surrounding nonpigmented naevus cells. OBJECTIVES: To investigate the
      effectiveness of combined treatment with the PDL and QsRL for large to giant CMN.
      METHODS: Six patients with large to giant CMN were enrolled in this study.
      Treatment consisted of one pass of PDL treatment followed by one pass of QsRL
      treatment. Multiple rounds of treatment were applied to all patients. RESULTS:
      All patients responded to this combined regimen, and the lesional colour was
      effectively reduced. The mean number of rounds of laser treatment required to
      achieve skin lightening was 7.7. No patients suffered severe hypertrophic
      scarring. No cases of recurrence or malignant transformation were observed. The
      histological results from the patient who underwent the most laser therapy in
      this study showed a remarkable reduction in the number of melanocytic naevus
      cells after treatment. CONCLUSIONS: This technique may enable the removal of most
      of the pigmented lesion and melanocytic naevus cells with minimal scarring.

PMID- 22591104
TI  - Detailed product analysis during low- and intermediate-temperature oxidation of
      ethylcyclohexane.
AB  - An experimental study of the oxidation of ethylcyclohexane has been performed in
      a jet-stirred reactor with online gas chromatography, under quasi-atmospheric
      pressure (800 Torr), at temperatures ranging from 500 to 1100 K (low- and
      intermediate-temperature zone including the negative temperature coefficient
      area), at a residence time of 2 s, and for three equivalence ratios (0.25, 1, and
      2). Ethylcyclohexane displays important low-temperature reactivity with a well
      marked negative temperature coefficient behavior. In addition to 47 products with
      a mass lower than ethylcyclohexane which have been quantified, many species with
      a C(8)H(14)O formula (molecular weight of 126) were detected by GC-MS and 7 of
      them were quantified. These molecules are cyclic ethers, ketones, and aldehydes
      with the same carbon skeleton as the reactant. Experiments were also carried on
      under the same conditions for two other C(8) hydrocarbons, n-octane and 1-octene,
      showing that the reactivity of ethylcyclohexane is close to that of the alkene
      and lower than that of the alkane. Simulations using a detailed kinetic model of
      the literature allow a good prediction of the global reactivity and of the main
      hydrocarbon products for temperatures above 800 K. The main reaction channels
      leading to the observed reaction products at both  low (below 800 K) and
      intermediate temperature (above 800 K) are discussed.

PMID- 22591105
TI  - High prevalence of overweight and obesity among 6-year-old children in Finnmark
      County, North Norway.
AB  - AIM: The aim was to determine the prevalence of overweight and obesity among 6
      year-old children in Finnmark, the northernmost county of Norway. METHODS: This
      is a survey of 1774 children born during 1999 and 2000 from 18 of 19 child
      healthcare centres in Finnmark. Body mass index data extracted retrospectively in
      2007 from health records at the age of 6 years were compared with international
      definitions of over- and underweight. The prevalence figures were further
      compared with socio-demographic figures on municipality level. RESULTS: Overall,
      19% of the children were classified as overweight or obese; 5% were classified as
      obese. The prevalence of overweight and obesity was higher among girls (22%) than
      among boys (16%) (p < 0.01). The prevalence of underweight was 8% among both
      girls and boys. Despite large variations in the prevalence of overweight and
      obesity between municipalities (9-35%), no association was found with
      municipality figures on socio-demographic factors. CONCLUSION: In the
      northernmost county Finnmark, the prevalence of overweight including obesity
      among 6-year-old children was somewhat higher than in previous surveys from
      Norway, especially among girls.

PMID- 22591106
TI  - Meta-analysis: IL28B polymorphisms predict sustained viral response in HCV
      patients treated with pegylated interferon-alpha and ribavirin.
AB  - BACKGROUND: Interleukin (IL) 28B single nucleotide polymorphisms can predict
      sustained virological response (SVR) in hepatitis C virus (HCV) patients
      following pegylated interferon-alpha (PEG IFN-alpha) and ribavirin treatment.
      AIM: To design a meta-analysis to determine IL28B genotypes', rs12979860 CC and
      rs8099917 TT, correlation with SVR in PEG IFN-alpha/ribavirin-treated HCV
      patients. METHODS: Meta-analysis was performed in 17 studies of rs12979860 CC vs.
      CT/TT and 17 of rs8099917 TT vs. TG/GG. Odds ratios (OR) and confidence intervals
      (95% CI) were calculated by fixed- or random-effects models. Heterogeneity,
      sensitivity analysis and publication bias were also assessed. RESULTS: Of 4252
      Asian, Caucasian and African HCV patients analysed for rs12979860, SVR was more
      frequent in CC (vs. CT/TT; OR = 4.76, 95% CI: 3.15-7.20). Moreover, CC was
      associated with SVR for HCV genotype-1 or -4 infections (OR(genotype 1) = 5.52,
      95% CI: 3.74-8.15; OR(genotype 4) = 8.11, 95% CI: 4.13-15.93), regardless of
      ethnicity. Of 4549 Caucasian and Asian HCV patients analysed for rs8099917, SVR
      was more frequent in TT (vs. TG/GG; OR = 3.31, 95% CI: 2.39-4.59). Moreover, TT
      was associated with SVR for HCV-1 (OR(genotype 1) = 4.28, 95% CI: 2.87-6.38).
      Rs8099917 TT predictive value was stronger in Asians (OR(Asians) = 8.09, 95% CI:
      5.63-11.61; OR(Caucasians) = 3.00, 95% CI: 2.03-4.45). Ethnicity stratification
      revealed that rs8099917 TT had slight predictive value in Asian HCV-2/3 patients
      (OR = 1.99, 95% CI: 1.09-3.62). CONCLUSIONS: IL28B rs12979860 CC and rs8099917 TT
      are strong SVR predictors for PEG IFN-alpha/ribavirin-treated HCV-1 patients,
      regardless of ethnicity. In HCV-2/3, rs12979860 CC has no SVR predictive value,
      but rs8099917 TT was slightly associated with SVR in Asians.

PMID- 22591107
TI  - Serum holotranscobalamine, vitamin B12, folic acid and homocysteine levels in
      alopecia areata patients.
AB  - Alopecia areata has been associated with many autoimmune diseases. There is a
      common belief that the prevalence of pernicious anemia is increased in patients
      with alopecia areata. In this study, we sought to investigate vitamin B12, folate
      and homocysteine metabolism in alopecia areata. We measured holotranscobalamine
      (holoTC), vitamin B12, folate and homocysteine levels in 75 patients with
      alopecia areata and 54 controls. We did not find any significant differences in
      these parameters between these groups. We think that alopecia areata may not be
      associated with vitamin B12 deficiency. The co-occurrence of pernicious anemia
      and alopecia areata in rare autoimmune syndromes, may not justify routine
      measurements of these parameters in alopecia areata patients.

PMID- 22591108
TI  - Headspace analysis of Italian and New Zealand parmesan cheeses.
AB  - New Zealand is a leader in the global dairy industry. Milk powder is the
      principal export product, but there is also a prominent cheese manufacturing
      industry, catering more for the domestic market. The Selected Ion Flow Tube-Mass
      Spectrometric (SIFT-MS) technique was used to compare 4 New Zealand cheeses
      marketed as "parmesan" with 4 Italian Parmigiano Reggiano and Grana Padano
      cheeses. The cheese headspace was analyzed in real time without any sample
      preconcentration. Total of 38 volatile compounds in the cheese headspace were
      monitored with headspace concentrations varying between single digit parts per
      billion (ppb) to tens of parts per million (ppm). When the results were subjected
      to multivariate statistical analysis, a clear discrimination was found between
      the New Zealand "parmesan" and Italian cheeses based solely on the measured
      concentrations of these volatile compounds. If the volatile compounds used in the
      analyses were restricted to known odor-active compounds in Parmigiano Reggiano
      cheese, the ability to discriminate between the cheeses was maintained. The
      analyses also showed that it was possible to clearly differentiate between the
      different processing plants in individual countries. Important discriminatory
      volatiles in the samples tested were butanoic acid and phenylacetaldehyde for
      discriminating between Italian cheeses and ethyl butyrate, acetaldehyde and
      methylbutanals between New Zealand cheeses. We conclude that the New Zealand
      "parmesans" do not provide a good representation of the aroma of Italian
      "parmesans." PRACTICAL APPLICATION: SIFT-MS has been shown to clearly
      differentiate both country of origin and the manufacturer of "parmesan" cheeses
      made in Italy and New Zealand based on differences in volatile organic compounds.
      Thus this method will have benefit for use in the quality control of "parmesan"
      and other cheese varieties.

PMID- 22591109
TI  - Influence of perspective on the neural correlates of motor resonance during
      natural action observation.
AB  - We investigated the neural correlates of motor resonance during the observation
      of natural transitive actions and determined how the observer's perspective
      modulates the neural activation. Seventeen right-handed participants observed
      right and left hand tool grasping actions from a first-person or third-person
      perspective while undergoing fMRI. A two-factorial analysis of variance over the
      parietal region revealed no main effects of hand identity or perspective, but
      unveiled a hand by perspective interaction effect. The first-person perspective
      elicited parietal activation in the hemisphere contralateral to the performing
      hand as if the modelled action was mimicked with the same anatomical hand. In the
      third-person perspective, parietal activation ipsilateral to the modelled hand
      was found, indicating a specular strategy, rather than an anatomical imitation.
      Motor resonance was maximal in three foci in the superior parietal lobule and
      intraparietal sulcus that have been associated with prehensile actions. Our
      results suggest that therapeutic strategies aimed to elicit motor resonance, such
      as motor imagery and observational modelling, can adjust their spatial frame of
      reference according to the hemisphere they intend to stimulate.

PMID- 22591110
TI  - Non-alpha-adrenergic effects on systemic vascular conductance during lower-body
      negative pressure, static exercise and muscle metaboreflex activation.
AB  - AIM: This study tested the hypothesis that non-alpha-adrenergic mechanisms
      contribute to systemic vascular conductance (SVC) in a reflex-specific manner
      during the sympathoexcitatory manoeuvres. METHODS: Twelve healthy subjects
      underwent lower-body negative pressure (LBNP, -40 mmHg) as well as static
      handgrip exercise (HG, 20% of maximal force) followed by post-exercise forearm
      circulatory occlusion (PECO, 5 min each) with and without alpha-adrenergic
      blockade induced by phentolamine (PHE). Aortic blood flow, finger blood pressure
      and superficial femoral artery blood flow were measured to calculate cardiac
      output, SVC and leg vascular conductance (LVC) during the last minute of each
      intervention. RESULTS: Mean arterial pressure (MAP) decreased more during LBNP
      with PHE compared with saline (-7 +/- 7 vs. -2 +/- 5%, P = 0.016). PHE did not
      alter the MAP response to HG (+20 +/- 12 and +24 +/- 16%, respectively, for PHE
      and saline) but decreased the change in MAP during PECO (+12 +/- 7 vs. +21 +/-
      14%, P = 0.005). The decrease in SVC and LVC with LBNP did not differ between
      saline and PHE trials (-13 +/- 10 vs. -17 +/- 10%, respectively, for SVC, P =
      0.379). In contrast, the SVC response to HG increased from -9 +/- 12 with saline
      to + 5 +/- 15% with PHE (P = 0.002) and from -16 +/- 15 with saline to +1 +/- 16%
      with PHE during PECO (P = 0.003). LVC responses to HG or PECO were not different
      from saline with PHE. CONCLUSIONS: Non-alpha-adrenergic vasoconstriction was
      present during LBNP. The systemic vasoconstriction during static exercise and
      isolated muscle metaboreflex activation, in the absence of leg vasoconstriction,
      was explained by an alpha-adrenergic mechanism. Therefore, non-alpha-adrenergic
      vasoconstriction is more emphasized during baroreflex, but not metaboreflex
      mediated sympathetic activation.

PMID- 22591111
TI  - Role of free radicals in modeling the iodide-peroxide reaction mechanism.
AB  - The mechanism of monotonous decomposition of hydrogen peroxide by iodide in
      acidic medium is investigated at room temperature. For this purpose, O(2)
      pressure, I(-), I(2), and I(3)(-) concentrations are simultaneously monitored,
      establishing a useful framework for better understanding of the reaction
      mechanism and testing various models. The possibility of nonradical and radical
      approaches to describe experimental data is examined. Results suggest that the
      best description of experimentally recorded components is obtained by introducing
      free radicals into the model of the reaction.

PMID- 22591112
TI  - Economic evaluation of smoking-cessation therapies: a critical and systematic
      review of simulation models.
AB  - BACKGROUND: Smoking is probably the most important among preventable health
      risks. Health economic evaluation of smoking-cessation interventions, applying a
      lifetime perspective, is made possible by available epidemiological knowledge.
      The well established method of performing cost-effectiveness analyses of smoking
      cessation interventions involves mathematical modelling (both deterministic and
      stochastic) of future events important for cost effectiveness. OBJECTIVES: This
      study surveys cost-effectiveness analyses of smoking cessation, with a particular
      focus on the mathematical modelling and simulation analyses performed. DATA
      SOURCES: A systematic literature search was performed using the databases
      MEDLINE, Econlit and Academic Search Complete. STUDY SELECTION: Health economic
      evaluations, published as full-length journal articles, were searched for.
      RESULTS: 423 studies were identified and 78 were finally included, of which 30
      were assessed as being highly relevant, based on the application of simulation
      modelling. CONCLUSIONS: In general, studies are well performed as regards
      modelling. Common weaknesses include reporting of modelling details; validation
      of used simulation models; and the handling of structural uncertainty and
      different types of heterogeneity.

PMID- 22591114
TI  - Structural and energetic basis of infection by the filamentous bacteriophage IKe.
AB  - Filamentous phage use the two N-terminal domains of their gene-3-proteins to
      initiate infection of Escherichia coli. One domain interacts with a pilus, and
      then the other domain binds to TolA at the cell surface. In phage fd, these two
      domains are tightly associated with each other, which renders the phage robust
      but non-infectious, because the TolA binding site is inaccessible. Activation for
      infection requires partial unfolding, domain disassembly and prolyl
      isomerization. Phage IKe infects E. coli less efficiently than phage fd. Unlike
      in phage fd, the pilus- and TolA-binding domains of phage IKe are independent of
      each other in stability and folding. The site for TolA binding is thus always
      accessible, but the affinity is very low. The structures of the two domains,
      analysed by X-ray crystallography and by NMR spectroscopy, revealed a unique fold
      for the N-pilus-binding domain and a conserved fold for the TolA-binding domain.
      The absence of an activation mechanism as in phage fd and the low affinity for
      TolA probably explain the low infectivity of phage IKe. They also explain why, in
      a previous co-evolution experiment with a mixture of phage fd and phage IKe, all
      hybrid phage adopted the superior infection mechanism of phage fd.

PMID- 22591113
TI  - Rational development of a cytotoxic peptide to trigger cell death.
AB  - Defects in the apoptotic machinery can contribute to tumor formation and
      resistance to treatment, creating a need to identify new agents that kill cancer
      cells by alternative mechanisms. To this end, we examined the cytotoxic
      properties of a novel peptide, CT20p, derived from the C-terminal, alpha-9 helix
      of Bax, an amphipathic domain with putative membrane binding properties. Like
      many antimicrobial peptides, CT20p contains clusters of hydrophobic and cationic
      residues that could enable the peptide to associate with lipid membranes. CT20p
      caused the release of calcein from mitochondrial-like lipid vesicles without
      disrupting vesicle integrity and, when expressed as a fusion protein in cells,
      localized to mitochondria. The amphipathic nature of CT20p allowed it to be
      encapsulated in polymeric nanoparticles (NPs) that have the capacity to harbor
      targeting molecules, dyes or drugs. The resulting CT20p-NPs proved an effective
      killer, in vitro, of colon and breast cancer cells, and in vivo, using a murine
      breast cancer tumor model. By introducing CT20p to Bax deficient cells, we
      demonstrated that the peptide's lethal activity was independent of endogenous
      Bax. CT20p also caused an increase in the mitochondrial membrane potential that
      was followed by plasma membrane rupture and cell death, without the
      characteristic membrane asymmetry associated with apoptosis. We determined that
      cell death triggered by the CT20p-NPs was minimally dependent on effector
      caspases and resistant to Bcl-2 overexpression, suggesting that it acts
      independently of the intrinsic apoptotic death pathway. Furthermore, use of CT20p
      with the apoptosis-inducing drug, cisplatin, resulted in additive toxicity. These
      results reveal the novel features of CT20p that allow nanoparticle-mediated
      delivery to tumors and the potential application in combination therapies to
      activate multiple death pathways in cancer cells. 

PMID- 22591115
TI  - A review of statistical estimators for risk-adjusted length of stay: analysis of
      the Australian and new Zealand Intensive Care Adult Patient Data-Base, 2008-2009.
AB  - BACKGROUND: For the analysis of length-of-stay (LOS) data, which is
      characteristically right-skewed, a number of statistical estimators have been
      proposed as alternatives to the traditional ordinary least squares (OLS)
      regression with log dependent variable. METHODS: Using a cohort of patients
      identified in the Australian and New Zealand Intensive Care Society Adult Patient
      Database, 2008-2009, 12 different methods were used for estimation of intensive
      care (ICU) length of stay. These encompassed risk-adjusted regression analysis of
      firstly: log LOS using OLS, linear mixed model [LMM], treatment effects, skew
      normal and skew-t models; and secondly: unmodified (raw) LOS via OLS, generalised
      linear models [GLMs] with log-link and 4 different distributions [Poisson, gamma,
      negative binomial and inverse-Gaussian], extended estimating equations [EEE] and
      a finite mixture model including a gamma distribution. A fixed covariate list and
      ICU-site clustering with robust variance were utilised for model fitting with
      split-sample determination (80%) and validation (20%) data sets, and model
      simulation was undertaken to establish over-fitting (Copas test). Indices of
      model specification using Bayesian information criterion [BIC: lower values
      preferred] and residual analysis as well as predictive performance (R2,
      concordance correlation coefficient (CCC), mean absolute error [MAE]) were
      established for each estimator. RESULTS: The data-set consisted of 111663
      patients from 131 ICUs; with mean(SD) age 60.6(18.8) years, 43.0% were female,
      40.7% were mechanically ventilated and ICU mortality was 7.8%. ICU length-of-stay
      was 3.4(5.1) (median 1.8, range (0.17-60)) days and demonstrated marked kurtosis
      and right skew (29.4 and 4.4 respectively). BIC showed considerable spread, from
      a maximum of 509801 (OLS-raw scale) to a minimum of 210286 (LMM). R2 ranged from
      0.22 (LMM) to 0.17 and the CCC from 0.334 (LMM) to 0.149, with MAE 2.2-2.4.
      Superior residual behaviour was established for the log-scale estimators. There
      was a general tendency for over-prediction (negative residuals) and for over
      fitting, the exception being the GLM negative binomial estimator. The mean
      variance function was best approximated by a quadratic function, consistent with
      log-scale estimation; the link function was estimated (EEE) as 0.152(0.019,
      0.285), consistent with a fractional-root function. CONCLUSIONS: For ICU length
      of stay, log-scale estimation, in particular the LMM, appeared to be the most
      consistently performing estimator(s). Neither the GLM variants nor the skew
      regression estimators dominated.

PMID- 22591116
TI  - Large improvement in the catalytic activity due to small changes in the diimine
      ligands: new mechanistic insight into the dirhodium(II,II) complex-based
      photocatalytic H2 production.
AB  - Two dirhodium(II) complexes, [Rh(II)(2)(MU-O(2)CCH(3))(2)(bpy)(2)](O(2)CCH(3))(2)
      (Rh(2)bpy(2); bpy = 2,2'-bipyridine) and [Rh(II)(2)(MU
      O(2)CCH(3))(2)(phen)(2)](O(2)CCH(3))(2) (Rh(2)phen(2); phen = 1,10
      phenanthroline) were synthesized, and their photocatalytic H(2) production
      activities were studied in multicomponent systems, containing
      [Ir(III)(ppy)(2)(dtbbpy)](+) (ppy = 2-phenylpyridine, dtbbpy = 4,4'-di-tert-butyl
      2,2'-bipyridine) as the photosensitizer (PS) and triethylamine as the sacrificial
      reductant (SR). There is a more than 6-fold increase in the photocatalytic
      activity from Rh(2)bpy(2) to Rh(2)phen(2) just using phen in place of bpy. A
      turnover number as high as 2622 was obtained after 50 h of irradiation of a
      system containing 16.7 MUM Rh(2)phen(2), 50 MUM PS, and 0.6 M SR. The
      electrochemical, luminescence quenching, and transient absorption experiments
      demonstrate that Rh(I)Rh(I) is the true catalyst for the proton reduction. The
      real-time absorption spectra confirm that a new Rh-based species formed upon
      irradiation of the Rh(2)phen(2)-based multicomponent system, which exhibits an
      absorption centered at ~575 nm. This 575-nm intermediate may account for the much
      higher H(2) evolution efficiency of Rh(2)phen(2). Our work highlights the
      importance of N-based chelate ligands and opens a new avenue for pursuing more
      efficient Rh(II)(2)-based complexes in photocatalytic H(2) production
      application.

PMID- 22591117
TI  - EEG Sigma and slow-wave activity during NREM sleep correlate with overnight
      declarative and procedural memory consolidation.
AB  - Previous studies suggest that sleep-specific brain activity patterns such as
      sleep spindles and electroencephalographic slow-wave activity contribute to the
      consolidation of novel memories. The generation of both sleep spindles and slow
      wave activity relies on synchronized oscillations in a thalamo-cortical network
      that might be implicated in synaptic strengthening (spindles) and downscaling
      (slow-wave activity) during sleep. This study further examined the association
      between electroencephalographic power during non-rapid eye movement sleep in the
      spindle (sigma, 12-16 Hz) and slow-wave frequency range (0.1-3.5 Hz) and
      overnight memory consolidation in 20 healthy subjects (10 men, 27.1 +/- 4.6
      years). We found that both electroencephalographic sigma power and slow-wave
      activity were positively correlated with the pre-post-sleep consolidation of
      declarative (word list) and procedural (mirror-tracing) memories. These results,
      although only correlative in nature, are consistent with the view that processes
      of synaptic strengthening (sleep spindles) and synaptic downscaling (slow-wave
      activity) might act in concert to promote synaptic plasticity and the
      consolidation of both declarative and procedural memories during sleep.

PMID- 22591118
TI  - Upper esophageal sphincter and esophageal motility in patients with chronic cough
      and reflux: assessment by high-resolution manometry.
AB  - The pathophysiology of chronic cough and its association with dsymotility and
      laryngopharyngeal reflux remains unclear. This study applied high-resolution
      manometry (HRM) to obtain a detailed evaluation of pharyngeal and esophageal
      motility in chronic cough patients with and without a positive reflux-cough
      symptom association probability (SAP). Retrospective analysis of 66 consecutive
      patients referred for investigation of chronic cough was performed. Thirty-four
      (52%) were eligible for inclusion (age 55 [19-77], 62% female). HRM (ManoScan
      360, Given/Sierra Scientific Instruments, Mountain View, CA) with 10 water
      swallows was performed followed by a 24-hour ambulatory pH monitoring. Of this
      group, 21 (62%) patients had negative reflux-cough SAP (group A) and 13 (38%) had
      positive SAP (group B). Results from 23 healthy controls were available for
      comparison (group C). Detailed analysis revealed considerable heterogeneity. A
      small number of patients had pathological upper esophageal sphincter (UES)
      function (n=9) or esophageal dysmotility (n=1). The overall baseline UES pressure
      was similar, but average UES residual pressure was higher in groups A and B than
      in control group C (-0.2 and -0.8mmHg vs. -5.4mmHg; P<0.018 and P<0.005). The
      percentage of primary peristaltic contractions was lower in group B than in
      groups A and C (56% vs. 79% and 87%; P=0.03 and P<0.002). Additionally,
      intrabolus pressure at the lower esophageal sphincter was higher in group B than
      in group C (15.5 vs. 8.9; P=0.024). HRM revealed changes to UES and esophageal
      motility in patients with chronic cough that are associated with impaired bolus
      clearance. These changes were most marked in group B patients with a positive
      reflux-cough symptom association.

PMID- 22591119
TI  - Cost-effectiveness of rituximab as maintenance therapy in patients with
      follicular non-Hodgkin lymphoma after responding to first-line rituximab plus
      chemotherapy.
AB  - A recent phase III trial demonstrated that maintenance rituximab(r) therapy after
      response to first-line treatment with rituximab plus chemotherapy (R-chemo)
      increases progression-free survival (PFS) for follicular non-Hodgkin lymphoma (f
      NHL). A cost-effectiveness analysis of R-maintenance versus observation was
      conducted from a US payer perspective to estimate PFS and overall survival (OS)
      over a representative patient's lifetime. Primary outcomes were cost per life
      year gained (LYG) and cost per quality-adjusted life-year (QALY) gained. Compared
      with observation, R-maintenance increased mean PFS by 1.50 years, OS by 1.21
      years and QALYs gained by 1.11 years. The incremental cost of maintenance therapy
      was $38,545. The costs per LYG and QALY gained were $31,934 and $34,842,
      respectively. Within the limitations of modeling long-term outcomes, R
      maintenance therapy in patients who received R-chemo for previously untreated f
      NHL compared with observation alone after R-chemo for first-line treatment for f
      NHL is cost-effective from the US payer perspective.

PMID- 22591120
TI  - Acknowledging island pedicle flaps for the repair of defects of the medial
      canthus.

PMID- 22591121
TI  - Randomised clinical trial: esomeprazole for the prevention of nonsteroidal anti
      inflammatory drug-related peptic ulcers in Japanese patients.
AB  - BACKGROUND: The use of proton pump inhibitors for prevention of nonsteroidal anti
      inflammatory drug (NSAID)-induced gastrointestinal adverse events is well
      documented. However, data regarding the efficacy and safety of this approach in
      Japan are scarce. AIM: To evaluate the efficacy and tolerability of esomeprazole
      in preventing NSAID-induced peptic ulcers in Japanese at-risk patients. METHODS:
      Male and female Japanese adult patients (aged >= 20 years) with endoscopically
      confirmed history of peptic ulcers who required long-term oral NSAID therapy for
      a chronic inflammatory condition were randomised to 24 weeks' treatment with
      esomeprazole 20 mg once daily or matching placebo. The primary end point was the
      Kaplan-Meier estimated proportion of ulcer-free patients. RESULTS: Overall, 343
      patients were randomised to treatment (esomeprazole, n = 175; placebo, n = 168).
      The Kaplan-Meier estimated ulcer-free rate over the 24-week treatment period was
      significantly higher (log-rank P < 0.001) in esomeprazole-treated patients
      (96.0%; 95% CI 92.8, 99.1) than in placebo recipients (64.4%; 95% CI 56.8, 71.9).
      Esomeprazole was effective at preventing peptic ulcers in both Helicobacter
      pylori-positive and -negative patients (96.3% vs. 95.5% of patients ulcer-free,
      respectively); however, in the placebo group, the proportion of ulcer-free
      patients at 24 weeks was markedly lower among H. pylori-positive than -negative
      patients (59.7% vs. 69.9%). The NSAID type did not seem to affect the estimated
      ulcer-free rate with esomeprazole. Treatment with esomeprazole was well
      tolerated. CONCLUSION: Esomeprazole 20 mg once daily is effective and safe in
      preventing ulcer recurrence in Japanese patients with a definite history of
      peptic ulcers who were taking an NSAID (ClinicalTrials.gov identifier:
      NCT00542789).

PMID- 22591122
TI  - Verification of the role of MlrC in microcystin biodegradation by studies using a
      heterologously expressed enzyme.
AB  - The MlrC protein from Sphingomonas ACM-3962 strain was heterologously expressed
      in Escherichia coli strain BL21(DE3) and purified to investigate participation of
      this enzyme in the biodegradation of two microcystin variants. In contrast with
      previous reports, our results indicated that MlrC cleaves linear microcystins,
      thus shedding new light on the role of MlrC enzyme in microcystin biodegradation.

PMID- 22591123
TI  - Doing, seeing, or both: effects of learning condition on subsequent action
      perception.
AB  - It has been proposed that common codes for vision and action emerge from
      associations between an individual's production and simultaneous observation of
      actions. This typically first-person view of one's own action subsequently
      transfers to the third-person view when observing another individual. We tested
      vision-action associations and the transfer from first-person to third-person
      perspective by comparing novel hand-action sequences that were learned under
      three conditions: first, by being performed and simultaneously viewed from a
      first-person perspective; second, by being performed but not seen; and third, by
      being seen from a first-person view without being executed. We then used
      functional magnetic resonance imaging (fMRI) to compare the response to these
      three types of learned action sequences when they were presented from a third
      person perspective. Visuomotor areas responded most strongly to sequences that
      were learned by simultaneously producing and observing the action sequences. We
      also note an important asymmetry between vision and action: Action sequences
      learned by performance alone, in the absence of vision, facilitated the emergence
      of visuomotor responses, whereas action sequences learned by viewing alone had
      comparably little effect. This dominance of action over vision supports the
      notion of forward/predictive models of visuomotor systems.

PMID- 22591124
TI  - Implementation and results of bedside hearing screening with automated auditory
      brainstem response in the neonatal intensive care unit.
AB  - AIM: To evaluate implementation and results of neonatal hearing screening with
      automated auditory brainstem response (AABR) by bedside nurses in a single-centre
      neonatal intensive care unit (NICU). METHODS: Retrospective review of charts of
      2074 newborns admitted over a 4-year period. RESULTS: One thousand eight hundred
      and 24 newborns (88%) were screened. A 'pass' result was obtained in 1761
      patients (96.5%). From 63 infants with 'refer', 40 were tested with auditory
      brainstem response: in 28 hearing loss was confirmed. Three hundred and nine
      neonates were screened before postmenstrual age (PMA) of 34 weeks: 78%
      successfully passed the first test. Sixty-seven infants with 'refer' at the first
      test before PMA of 34 weeks were re-evaluated: 48 had normal hearing tests, 24 of
      whom still younger than 34 weeks. For 12 of 19 infants with 'refer' before 34
      weeks, follow-up was available: in 7 hearing loss was confirmed. CONCLUSION:
      Neonatal hearing screening with AABR can be easily performed by the bedside nurse
      in the NICU even in premature babies before 34 weeks PMA. A 'pass' result can be
      obtained in almost 80% of them; a 'refer' result at that age, however, must be
      interpreted cautiously, as false 'refer' occurred in 5/12 of these infants.

PMID- 22591127
TI  - Fatty acid composition of selected macrophytes.
AB  - The content of total lipids and the fatty acid (FA) profile were determined for
      eight macroalgae (Cystoseira abies-marina, Fucus spiralis, Chaetomorpha
      pachynema, Codium elisabethae, Porphyra sp., Osmundea pinnatifida, Pterocladiella
      capillacea and Sphaeroccoccus coronopifolius). Total lipids were extracted using
      a solvent mixture of methanol/chloroform (2/1, v/v) and further derivatised to FA
      methyl esters (FAME). The analyses of FAME samples were performed by gas
      chromatography coupled to a flame ionisation detector. The total lipid content
      ranged from 0.06 to 3.54 g (per 100 g). The most abundant saturated FA were
      palmitic (C16:0) and myristic (C14:0), while oleic (C18:1 n-9) was the dominant
      monounsaturated acid. All seaweeds contained linoleic FA (C18:2 n-6). The alpha
      linolenic (C18:3 n-3) and eicosapentaenoic (20:5 n-3) acids were present only in
      Porphyra sp. (3.34% +/- 0.13) and C. pachynema (0.47% +/- 0.12), respectively.
      The n-6/n-3 and h/H ratios were low, suggesting a high nutritional value of the
      algae studied.

PMID- 22591128
TI  - Moisture desorption rates from TATB formulations: experiments and kinetic models.
AB  - The rate of water desorption from PBX-9502, a formulation containing 1,3,5
      triamino-2,4,6-trinitrobenzene (TATB), is measured using temperature-programmed
      desorption and modeled using conventional kinetic modeling methods. The results
      of these studies show two stages of moisture release. At lower temperatures, the
      release is likely assisted by thermal expansion of the TATB and melting of the
      Kel-F binder. At higher temperatures, a considerable amount of water is released
      and is attributed to sublimation of the TATB, which exposes new surfaces for
      water desorption.

PMID- 22591126
TI  - Factors other than genotype account largely for the phenotypic variation of the
      pulmonary valve in Syrian hamsters.
AB  - Understanding of the aetiology of congenitally anomalous pulmonary valves remains
      incomplete. The aim of our study, therefore, was to elucidate the degree to which
      the phenotypic variation known to exist for the pulmonary valve relies on
      genotypic variation. Initially, we tested the hypothesis that genetically alike
      individuals would display similar valvar phenotypes if the phenotypic arrangement
      depended entirely, or almost entirely, on the genotype. Thus, we examined
      pulmonary valves from 982 Syrian hamsters belonging to two families subject to
      systematic inbreeding by crossing siblings. Their coefficient of inbreeding was
      0.999 or higher, so they could be considered genetically alike. External
      environmental factors were standardized as much as possible. A further 97 Syrian
      hamsters from an outbred colony were used for comparative purposes. In both the
      inbred and outbred hamsters, we found valves with a purely trifoliate, or
      tricuspid, design, trifoliate valves with a more or less extensive fusion of the
      right and left leaflets, bifoliate, or bicuspid, valves with fused right and left
      leaflets, with or without a raphe located in the conjoined arterial sinus, and
      quadrifoliate, or quadricuspid, valves. The incidence of the different valvar
      morphological variants was similar in the outbred and inbred colonies, except for
      the bifoliate pulmonary valves, which were significantly more frequent in the
      hamsters from one of the two inbred families. Results of crosses between
      genetically alike hamsters revealed no significant association between the
      pulmonary valvar phenotypes as seen in the parents and their offspring. The
      incidence of bifoliate pulmonary valves, nonetheless, was higher than
      statistically expected in the offspring of crosses where at least one of the
      parents possessed a pulmonary valve with two leaflets. Our observations are
      consistent with the notion that the basic design of the pulmonary valve, in terms
      of whether it possesses three or two leaflets, relies on genotypic determinants.
      They also denote that the bifoliate condition of the valve is the consequence of
      complex inheritance, with reduced penetrance and variable expressivity. Moreover,
      in showing that the incidence of the bifoliate pulmonary valve significantly
      differs in two different isogenetic backgrounds, our data suggest that genetic
      modifiers might be implicated in directing the manifestation of such specific
      pulmonary valvar malformations. Finally, our findings indicate that factors other
      than the genotype, operating during embryonic life and creating developmental
      noise, or random variation, play a crucial role in the overall phenotypic
      variation involving the pulmonary valve.

PMID- 22591129
TI  - Value of information and pricing new healthcare interventions.
AB  - Previous application of value-of-information methods to optimal clinical trial
      design have predominantly taken a societal decision-making perspective,
      implicitly assuming that healthcare costs are covered through public expenditure
      and trial research is funded by government or donation-based philanthropic
      agencies. In this paper, we consider the interaction between interrelated
      perspectives of a societal decision maker (e.g. the National Institute for Health
      and Clinical Excellence [NICE] in the UK) charged with the responsibility for
      approving new health interventions for reimbursement and the company that holds
      the patent for a new intervention. We establish optimal decision making from
      societal and company perspectives, allowing for trade-offs between the value and
      cost of research and the price of the new intervention. Given the current level
      of evidence, there exists a maximum (threshold) price acceptable to the decision
      maker. Submission for approval with prices above this threshold will be refused.
      Given the current level of evidence and the decision maker's threshold price,
      there exists a minimum (threshold) price acceptable to the company. If the
      decision maker's threshold price exceeds the company's, then current evidence is
      sufficient since any price between the thresholds is acceptable to both. On the
      other hand, if the decision maker's threshold price is lower than the company's,
      then no price is acceptable to both and the company's optimal strategy is to
      commission additional research. The methods are illustrated using a recent
      example from the literature.

PMID- 22591131
TI  - Ethanol enhances human hyperpolarization-activated cyclic nucleotide-gated
      currents.
AB  - BACKGROUND: There is a clear association between excessive ethanol ( EtOH )
      consumption and the risk of sudden cardiac death. The hyperpolarization-activated
      cyclic nucleotide-gated (HCN) current, I (f) , is known to contribute to
      spontaneous pacemaker activity of sinoatrial (SA) node cells. However, the exact
      mechanisms of EtOH on arrhythmia induction are not well understood. METHODS: The
      preparations of SA node were excised from rabbit heart, transmembrane potentials
      were recorded by standard glass microelectrode technique, and a whole-cell patch
      clamp technique was used to record I (f)  in enzymatically isolated rabbit SA
      node pacemaker cells. Human HCN2 (hHCN2) and HCN4 channels were heterologously
      expressed in Xenopus oocytes and studied using 2-electrode voltage clamp
      technique. RESULTS: Superfusion of EtOH increased the spontaneous firing
      frequency of SA node cells in a reversible fashion. Treatment with ivabradine
      irreversibly depressed basal firing frequency and markedly attenuated the
      enhancement effect of EtOH on firing. The stimulatory effects of EtOH on I (f) 
      were concentration-dependent in the range of 1 to 100 mM, with an average EC (50)
      value of 20.81 +/- 6.71 mM and Hill coefficient of 1.19 +/- 0.10. Furthermore,
      EtOH reversibly enhanced the HCN currents in a concentration-dependent fashion
      with an EC (50)  value of 18.41 +/- 2.75 mM for the HCN2 channel and 21.98 +/-
      3.54 mM for the HCN4 channel, which was accompanied by the acceleration of
      activation and deactivation kinetics. In addition, EtOH , at both moderate and
      high doses, caused a shift in the voltage dependence of hHCN4 channel activation
      to more depolarizing potentials. However, superfusion of high, not moderate,
      concentration of EtOH caused a shift in the voltage dependence of hHCN2 channel
      activation to more hyperpolarizing potentials. CONCLUSIONS: This study provides
      insight into the molecular interaction of EtOH and the hHCN channels, which may
      shed light on elucidating the potentially proarrhythmic mechanism of EtOH .

PMID- 22591130
TI  - Cost effectiveness of quetiapine in patients with acute bipolar depression and in
      maintenance treatment after an acute depressive episode.
AB  - BACKGROUND: Bipolar disorder has a significant impact upon a patient's quality of
      life, imposing a considerable economic burden on the individual, family members
      and society as a whole. Several medications are indicated for the acute treatment
      of mania and depression associated with bipolar disorder as well as for
      maintenance therapy; however, these have varying efficacy, tolerability and
      costs. OBJECTIVE: The objective of this study was to develop a new discrete-event
      simulation model to analyse the long-term consequences of pharmacological therapy
      for the management of bipolar I and II disorders (acute treatment of episodes of
      mania and depression as well as maintenance therapy). METHODS: Probabilities of
      remission and relapse were obtained from clinical trial data and meta-analyses.
      Costs (year 2011 values) were assessed from a UK healthcare payer's perspective,
      and included pharmacological therapy and resource use associated with the
      treatment of mood events and selected adverse events. The health effects were
      measured in terms of QALYs. RESULTS: For a patient starting with acute depression
      or in remission at 40 years of age (which was the average age in the clinical
      trials), quetiapine 300 mg/day was a cost-effective strategy compared with
      olanzapine 15 mg/day over a 5-year time frame. With acute bipolar depression as a
      starting episode, the 5-year medical costs were L323 higher and QALYs were 0.038
      higher for quetiapine compared with olanzapine, corresponding to a cost
      effectiveness ratio of L8600 per QALY gained. CONCLUSION: Compared with
      olanzapine, the results suggest that quetiapine is cost effective as a
      maintenance treatment for bipolar depression.

PMID- 22591132
TI  - Tales of tethers and tentacles: golgins in plants.
AB  - As plant Golgi bodies move through the cell along the actin cytoskeleton, they
      face the need to maintain their polarized stack structure whilst receiving,
      processing and distributing protein cargo destined for secretion. Structural
      proteins, or Golgi matrix proteins, help to hold cisternae together and tethering
      factors direct cargo carriers to the correct target membranes. This review
      focuses on golgins, a protein family containing long coiled-coil regions,
      summarizes their known functions in animal cells and highlights recent findings
      about plant golgins and their putative roles in the plant secretory pathway.

PMID- 22591133
TI  - Valuable insight into the anticancer activity of the platinum-histone deacetylase
      inhibitor conjugate, cis-[Pt(NH3)2malSAHA-2H)].
AB  - cis-[Pt(II)(NH3)2(malSAHA-2H)], a cisplatin adduct conjugated to a potent histone
      deacetylase inhibitor (HDACi), suberoylanilide hydroxamic acid (SAHA), was
      previously developed as a potential anticancer agent. This Pt-HDACi conjugate was
      demonstrated to have comparable cytotoxicity to cisplatin against A2780 ovarian
      cancer cells but significantly reduced cytotoxicity against a representative
      normal cell line, NHDF. Thus, with a view to (i) understanding more deeply the
      effects that may play an important role in the biological (pharmacological)
      properties of this new conjugate against cancer cells and (ii) developing the
      next generation of Pt-HDACi conjugates, the cytotoxicity, DNA binding, cellular
      accumulation and HDAC inhibitory activity of cis-[Pt(II)(NH3)2(malSAHA-2H)] were
      investigated and are reported herein. cis-[Pt(II)(NH3)2(malSAHA-2H)] was found to
      have marginally lower cytotoxicity against a panel of cancer cell lines as
      compared to cisplatin and SAHA. cis-[Pt(II)(NH3)2(malSAHA-2H)] was also found to
      accumulate better in cancer cells but bind DNA less readily as compared to
      cisplatin. DNA binding experiments indicated that cis-[Pt(II)(NH3)2(malSAHA-2H)]
      bound DNA more effectively in cellulo as compared to in cell-free media.
      Activation of the Pt-HDACi conjugate was therefore investigated. The binding of
      cis-[Pt(II)(NH3)2(malSAHA-2H)] to DNA was found to be enhanced by the presence of
      thiol-containing molecules such as glutathione and thiourea, and activation
      occurred in cytosolic but not nuclear extract of human cancer cells. The activity
      of cis-[Pt(NH3)2(malSAHA-2H)] as a HDAC inhibitor was also examined; the
      conjugate exhibited no inhibition of HDAC activity in CH1 cells. In light of
      these results, novel Pt-HDACi conjugates are currently being developed, with
      particular emphasis, through subtle structural modifications, on enhancing the
      rate of DNA binding and enhancing HDAC inhibitory activity. 

PMID- 22591135
TI  - Regulation of cholesterol biosynthetic pathway in different regions of the rat
      central nervous system.
AB  - AIM: In this study, we investigated the regulatory network of the key and rate
      limiting enzyme of cholesterol biosynthetic pathway, the 3-hydroxy 3
      methylglutaryl coenzyme A reductase (HMGR) in different brain regions, to add new
      insight about lipid metabolism and physiology in the central nervous system
      (CNS). METHODS: HMGR levels and activation state and the proteins involved in the
      enzyme regulatory network were analysed by Western blot in hippocampus, cortex,
      cerebellum and brain stem of adult male rats. RESULTS: HMGR protein level and
      phosphorylation state exhibit a specific pattern in each brain area analysed,
      according to the levels and activation state of the proteins responsible for the
      short- and long-term regulation of the enzyme. Moreover, low-density lipoprotein
      receptor expression displays a similar trend to that of HMGR. CONCLUSIONS: The
      obtained data indicate that cholesterol biosynthesis could be differently
      modulated in each brain region in adult male rat and emphasize marked differences
      in HMGR and low-density lipoprotein receptor regulation. The results provide new
      insights into the intricate network that regulates cholesterol homoeostasis in
      the adult CNS in connection with the regional needs of this molecule.

PMID- 22591134
TI  - Barriers to successful recruitment of parents of overweight children for an
      obesity prevention intervention: a qualitative study among youth health care
      professionals.
AB  - BACKGROUND: The recruitment of participants for childhood overweight and obesity
      prevention interventions can be challenging. The goal of this study was to
      identify barriers that Dutch youth health care (YHC) professionals perceive when
      referring parents of overweight children to an obesity prevention intervention.
      METHODS: Sixteen YHC professionals (nurses, physicians and management staff) from
      eleven child health clinics participated in semi-structured interviews. An
      intervention implementation model was used as the framework for conducting,
      analyzing and interpreting the interviews. RESULTS: All YHC professionals were
      concerned about childhood obesity and perceived prevention of overweight and
      obesity as an important task of the YHC organization. In terms of frequency and
      perceived impact, the most important impeding factors for referring parents of
      overweight children to an intervention were denial of the overweight problem by
      parents and their resistance towards discussing weight issues. A few YHC
      professionals indicated that their communication skills in discussing weight
      issues could be improved, and some professionals mentioned that they had low self
      efficacy in raising this topic. CONCLUSIONS: We consider it important that YHC
      professionals receive more training to increase their self-efficacy and skills in
      motivating parents of overweight children to participate in obesity prevention
      interventions. Furthermore, parental awareness towards their child's overweight
      should be addressed in future studies.

PMID- 22591137
TI  - Reviewing responsibilities and renewing relationships: an intervention with men
      on violence against women in India.
AB  - Violence against women is increasingly seen as a key women's rights issue in
      India. Some efforts to address it have started to engage men. The current study
      focuses on the impacts of Men's Action to Stop Violence Against Women (MASVAW), a
      network of men working on gender-based violence in the state of Uttar Pradesh, in
      India. The purpose of the study was to determine the extent to which MASVAW
      activists incorporate gender-equitable attitudes and practices into their own
      lives and to identify their influence on men around them. The cross-sectional
      study includes three groups: activists, men living in an area where activists
      conducted outreach activities and a control group living in an area with no
      MASVAW activities. Both activists and activist influenced men scored higher on
      measures of gender-equitable beliefs and practices than controls, suggesting that
      MASVAW activism is successful. Furthermore, men from the activist influenced
      group scored higher in gender progressiveness even if they did not have contact
      with MASVAW themselves, suggesting a diffusion effect of social change. However,
      there were some areas where the activists had low scores, suggesting need for
      additional inputs.

PMID- 22591136
TI  - Exploring post-translational arginine modification using chemically synthesized
      methylglyoxal hydroimidazolones.
AB  - The methylglyoxal-derived hydroimidazolones (MG-Hs) comprise the most prevalent
      class of non-enzymatic, post-translational modifications of protein arginine
      residues found in nature. These adducts form spontaneously in the human body, and
      are also present at high levels in the human diet. Despite numerous lines of
      evidence suggesting that MG-H-arginine adducts play critical roles in both
      healthy and disease physiology in humans, detailed studies of these molecules
      have been hindered by a lack of general synthetic strategies for their
      preparation in chemically homogeneous form, and on scales sufficient to enable
      detailed biochemical and cellular investigations. To address this limitation, we
      have developed efficient, multigram-scale syntheses of all MG-H-amino acid
      building blocks, suitably protected for solid-phase peptide synthesis, in 2-3
      steps starting from inexpensive, readily available starting materials. Thus, MG-H
      derivatives were readily incorporated into oligopeptides site-specifically using
      standard solid-phase peptide synthesis. Access to synthetic MG-H-peptide adducts
      has enabled detailed investigations, which have revealed a series of novel and
      unexpected findings. First, one of the three MG-H isomers, MG-H3, was found to
      possess potent, pH-dependent antioxidant properties in biochemical and cellular
      assays intended to replicate redox processes that occur in vivo. Computational
      and mechanistic studies suggest that MG-H3-containing constructs are capable of
      participating in mechanistically distinct H-atom-transfer and single-electron
      transfer oxidation processes. Notably, the product of MG-H3 oxidation was
      unexpectedly observed to disassemble into the fully unmodified arginine residue
      and pyruvate in aqueous solution. We believe these observations provide insight
      into the role(s) of MG-H-protein adducts in human physiology, and expect the
      synthetic reagents reported herein to enable investigations into non-enzymatic
      protein regulation at an unprecedented level of detail.

PMID- 22591138
TI  - A templated method to Bi2WO6 hollow microspheres and their conversion to double
      shell Bi2O3/Bi2WO6 hollow microspheres with improved photocatalytic performance.
AB  - Bi(2)WO(6) hollow microspheres with dimension of ca. 1.5 MUm were synthesized via
      a hydrothermal method using polystyrene particles as the template. The as
      prepared Bi(2)WO(6) hollow microspheres can be further transformed to double
      shell Bi(2)O(3)/Bi(2)WO(6) hollow microspheres. The samples were fully
      characterized by X-ray diffraction, scanning electron microscopy, transmission
      electron microscopy (TEM), high-resolution TEM, N(2)-sorption Brunauer-Emmett
      Teller surface area, UV-vis diffuse-reflectance spectroscopy, and X-ray
      photoelectron spectroscopy. The as-formed double-shell Bi(2)O(3)/Bi(2)WO(6)
      hollow microspheres exhibit enhanced photocatalytic activity due to the hollow
      nature and formation of the p-n junction between p-type Bi(2)O(3) and n-type
      Bi(2)WO(6). The study provides a general and effective method in the fabrication
      of composition and dimension-tunable composite hollow microspheres with sound
      heterojunctions that may show a variety of applications.

PMID- 22591139
TI  - The effect of the flavonol morin on adhesion and aggregation of Streptococcus
      pyogenes.
AB  - The effect of the flavonol morin on Streptococcus pyogenes biofilm growth was
      determined using a static biofilm model, in which reduced biofilm biomass was
      observed in the presence of morin, suggesting that morin inhibited biofilm
      development. Morin at concentrations exceeding 225 MUM had the greatest impact on
      biofilm biomass causing reductions of up to 65%, which was found to be
      statistically significant. Morin was also shown to induce rapid bacterial
      aggregation. Approximately 55% of S. pyogenes in liquid suspension aggregated
      when incubated with morin at concentrations of 275 and 300 MUM for 120 min,
      compared to the control group in which only 10% of the cells aggregated, this was
      also shown to be statistically significant.

PMID- 22591140
TI  - Adali N, Mars M, Petrie A, Noar J, Somerlad B. Presurgical orthopedics has no
      effect on archform in unilateral cleft lip and palate. Cleft Palate Craniofac J.
      2012;49(1):5-13.

PMID- 22591142
TI  - Remission of arthritis after esophagectomy in three patients with severe
      achalasia.
AB  - In the 1960s and 1970s, intestinal bypass surgery was performed to treat patients
      with extreme obesity. However, this is now done with great restriction due to the
      risk of complications, for instance, polyarthritis. An association between severe
      achalasia and arthritis has also been described, but very few articles on this
      topic are cited in PubMed, and most of the published case reports are old. In
      this article, we present a retrospective case series of three patients with
      severe achalasia and arthritis from the departments of rheumatology and surgery
      at a university hospital. The complaints from the esophagus as well as arthritis
      were resolved after esophagectomy and esophageal reconstruction. We conclude that
      severe achalasia can be associated with arthritis, and both can be cured by
      esophageal reconstruction. Thus, we want to remind of this rare, but probably
      largely unrecognized, association between achalasia and joint disease.

PMID- 22591141
TI  - Processing by rhomboid protease is required for Providencia stuartii TatA to
      interact with TatC and to form functional homo-oligomeric complexes.
AB  - The twin arginine transport (Tat) system transports folded proteins across the
      prokaryotic cytoplasmic membrane and the plant thylakoid membrane. In Escherichia
      coli three membrane proteins, TatA, TatB and TatC, are essential components of
      the machinery. TatA from Providencia stuartii is homologous to E. coli TatA but
      is synthesized as an inactive pre-protein with an N-terminal extension of eight
      amino acids. Removal of this extension by the rhomboid protease AarA is required
      to activate P. stuartii TatA. Here we show that P. stuartii TatA can functionally
      substitute for E. coli TatA provided that the E. coli homologue of AarA, GlpG, is
      present. The oligomerization state of the P. stuartii TatA pro-protein was
      compared with that of the proteolytically activated protein and with E. coli
      TatA. The pro-protein still formed small homo-oligomers but cannot form large
      TatBC-dependent assemblies. In the absence of TatB, E. coli TatA or the processed
      form of P. stuartii TatA form a complex with TatC. However, this complex is not
      observed with the pro-form of P. stuartii TatA. Taken together our results
      suggest that the P. stuartii TatA pro-protein is inactive because it is unable to
      interact with TatC and cannot form the large TatA complexes required for
      transport.

PMID- 22591143
TI  - Hotel-based ambulatory care for complex cancer patients: a review of the
      University College London Hospital experience.
AB  - Since 2005, University College London Hospital (UCLH) has operated a hotel-based
      Ambulatory Care Unit (ACU) for hematology and oncology patients requiring
      intensive chemotherapy regimens and hematopoietic stem cell transplants. Between
      January 2005 and 2011 there were 1443 patient episodes, totaling 9126 patient
      days, with increasing use over the 6-year period. These were predominantly for
      hematological malignancy (82%) and sarcoma (17%). Median length of stay was 5
      days (range 1-42), varying according to treatment. Clinical review and treatment
      was provided in the ACU, with patients staying in a local hotel at the hospital's
      expense. Admission to the inpatient ward was arranged as required, and there was
      close liaison with the inpatient team to preempt emergency admissions. Of the 523
      unscheduled admissions, 87% occurred during working hours. An ACU/hotel-based
      treatment model can be safely used for a wide variety of cancers and treatments,
      expanding hospital treatment capacity, and freeing up inpatient beds for those
      patients requiring them.

PMID- 22591144
TI  - Nurse managers - a professional scope of responsibilities.

PMID- 22591145
TI  - Global nurse leader perspectives on health systems and workforce challenges.
AB  - AIM: As part of the 2011 annual American Organization of Nurse Executives
      conference held in San Diego, California, a session was presented that focused on
      nursing workforce and health systems challenges from a global perspective. This
      article includes content addressed during the session representing nurse leader
      perspectives from the UK, Singapore and the USA. BACKGROUND: Recent events in
      global economic markets have highlighted the interdependence of countries. There
      is now a global focus on health-care costs and quality as government leaders
      struggle to reduce budgets and remain solvent. EVALUATION: Finding solutions to
      these complex problems requires that nurse leaders adopt more of a world view and
      network with one another as they look for best practices and creative strategies.
      KEY ISSUES: Nursing leadership challenges such as staffing, competency
      development, ageing populations, reduced health-care funding and maintaining
      quality are now common global problems. CONCLUSION: There is a need for
      innovation in nursing practice to accommodate the enormous challenges facing
      nursing's future. IMPLICATIONS FOR NURSING MANAGEMENT: Opportunities on an
      international scale for nurse leaders to have dialogue and network, such as the
      conference presentation discussed in this article, will become increasingly more
      important to facilitate the development of innovative leadership strategies.

PMID- 22591146
TI  - Attracting and maintaining the Y Generation in nursing: a literature review.
AB  - OBJECTIVE: This paper explores the literature related to attracting the Y
      Generation (Y Gen: people born between 1980 and 2000) to the nursing profession
      and retaining them in our current workforce. DESIGN: A comprehensive review of
      the literature supported the need for further research. Three searches were
      conducted and all relevant literature was reviewed by each researcher. Literature
      included in the review was chosen based on specific search-term inclusion. DATA
      SOURCES: Structured searches were conducted with no limitations on publication
      type, date or language. Search engines used included: Australian Family and
      Society, CINAHL, Expanded Academic, Google Scholar, Medline, ProQuest and PubMed.
      RESULTS: A critical review of the literature, particularly empirical work on the
      subject has informed decision making regarding the research questions that remain
      to be explored. CONCLUSIONS: The literature revealed that the Y Gen is currently
      contributing to the nursing workforce demographics. Much discussion exists
      surrounding the integration of the Y Gen into the workplace along with the other
      three generations of nurses. There is also an abundance of descriptions of the Y
      Gen characteristics and values. There is, however, limited reference relating to
      what attracted this generation to nursing or what might retain them in the
      nursing workforce. IMPLICATIONS FOR NURSING MANAGEMENT: The Y Gen is the largest
      generation to enter our workforce since the Baby Boomers. Health services need to
      recognize the needs of the Y Gen nurses and develop strategies to move the
      profession forward by preparing the current workforce and environment for a
      generation that is already here. The focus should be on their strengths with
      development made to structure a workforce that will support the Y Gen in their
      professional nursing role. Understanding what attracts the Y Gen to nursing, what
      managers can do to retain the Y Gen in nursing and how the nursing profession can
      support the Y Gen to assume a role in nursing and nursing governance will ensure
      that the retiring generation has left the nursing profession in capable hands.

PMID- 22591147
TI  - Psychological empowerment and job satisfaction between Baby Boomer and Generation
      X nurses.
AB  - AIM: This paper is a report of a study of differences in nurses' generational
      psychological empowerment and job satisfaction. BACKGROUND: Generations differ in
      work styles such as autonomy, work ethics, involvement, views on leadership, and
      primary views on what constitutes innovation, quality, and service. METHOD: A
      secondary analysis was conducted from two data sets resulting in a sample of 451
      registered nurses employed at five hospitals in West Virginia. One data set was
      gathered from a convenience sample and one from a randomly selected sample. Data
      were collected from 2000 to 2004. RESULTS: Baby Boomer nurses reported higher
      mean total psychological empowerment scores than Generation X nurses. There were
      no differences in total job satisfaction scores between the generations.
      CONCLUSION: There were significant differences among the generations'
      psychological empowerment scores. Generational differences related to
      psychological empowerment could provide insight into inconsistent findings
      related to nurse job satisfaction. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse
      administrators may consider this evidence when working on strategic plans to
      motivate and entice Generation X nurses and retain Baby Boomers. Although
      implications based on this study are tentative, the results indicate the need for
      administrators to consider the differences between Baby Boomer and Generation X
      nurses.

PMID- 22591148
TI  - Job satisfaction in birth cohorts of nurses.
AB  - AIM: The aim of the present study was to investigate which hospital, unit and
      individual characteristics predict job satisfaction in four age cohorts of
      registered nurses (RNs). BACKGROUND: Adequate supply of direct care nurses in
      hospitals is paramount to the provision of safe patient care. While recruitment
      is important, interventions to retain experienced nurses in the work force should
      also be undertaken. METHODS: Cross-sectional survey data from the 2004 National
      Database of Nursing Quality Indicators((r)) (NDNQI((r)) ) RN Survey with Job
      Satisfaction Scales((c)) were used. The sample included 53 851 RNs age 20-59
      years divided into four age cohorts. Data were analysed using three-level
      hierarchical linear modelling. RESULTS: Overtime demand and involuntary floating
      resulted in significantly lower job satisfaction in all age cohorts. The oldest
      two cohorts reported higher job satisfaction with increased unit tenure whereas
      the youngest cohort reported decreased job satisfaction with increased unit
      tenure. Higher job satisfaction was reported in all cohorts within Magnet
      hospitals; however, the relationship was only significant in 40-49 year olds.
      CONCLUSIONS: Some factors are associated with job satisfaction in all age
      cohorts. Other factors differentially influence job satisfaction based on the
      cohort group. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse leaders should consider
      retention strategies congruent with the job satisfaction predictors of different
      age groups.

PMID- 22591149
TI  - Job and career satisfaction and turnover intentions of newly graduated nurses.
AB  - AIM: To describe new graduate nurses' worklife experiences in Ontario hospital
      settings in the first 2 years of practice and to examine predictors of job and
      career satisfaction and turnover intentions. BACKGROUND: With a large cohort of
      nurses approaching retirement, every effort must be made to ensure that the work
      environments of new graduate nurses are positive, promoting job satisfaction and
      commitment to the profession to address the nursing workforce shortage. METHOD: A
      cross-sectional analysis of data from a mail survey of new graduate nurses
      (n=342) in their first and second year of experience was used to address the
      research objectives. RESULTS: Overall, new graduate nurses were positive about
      their working conditions and there were few differences between nurses in their
      first and second years of practice. Structural and personal factors explained
      significant amounts of variance (31-68%) in both job and career satisfaction and
      turnover intentions. Empowerment, work engagement and burnout were important
      significant predictors. CONCLUSIONS: Modifiable workplace factors play an
      important role in influencing new graduates' job and career satisfaction and
      turnover intentions. IMPLICATIONS FOR NURSING MANAGEMENT: Managers can employ
      strategies to enhance quality work environments that promote retention of new
      graduates and lessen the nursing workforce shortage.

PMID- 22591150
TI  - What do graduate registered nurses want from jobs in rural/remote Australian
      communities?
AB  - AIM: To explore and describe the needs of new graduate registered nurses in a
      rural and remote (R&R) setting within Australia. BACKGROUND: Rural practice has
      distinctive challenges for nurses. Nurses make up the largest and most widely
      distributed health workforce in Australia, outnumbering doctors 8:1 in R&R areas.
      EVALUATION: Literature was used to evaluate the graduate registered nurses' needs
      in R&R communities. KEY ISSUES: Three main themes emerged: expectations, support
      and workloads. Themes reflected enablers and disablers of retention of nurses as
      they transition from student role to new graduate practice. CONCLUSION: New
      graduates are aware of their limitations as new practitioners. There is an
      expectation that their employers will provide a supportive learning environment
      for them to gain the skills necessary to become proficient and valuable
      employees. IMPLICATIONS FOR NURSING MANAGEMENT: This commentary paper identifies
      the need for a structured, supported new graduate programme that recognizes and
      meets the needs, both clinical and social, of new graduate registered nurses in
      the R&R context.

PMID- 22591151
TI  - Factors contributing to contemporary nursing shortage in Macao.
AB  - AIM: The purpose of the study was to examine the reasons for a shortage of nurses
      in Macao, a Special Administrative Region (SAR) of the People's Republic of
      China. BACKGROUND: Macao is facing a problem that is confronting many other
      cities or countries in the developed world, namely a shortage of nursing
      professionals. Increasing shortages are affecting the quality of patient care as
      well as patient outcomes. METHODS: This research study used a qualitative
      approach to explore and understand the experiences of nurses affected by the
      manpower shortage. All interviews were transcribed verbatim to convey the
      interviewees' intended messages as accurately as possible. RESULTS AND
      CONCLUSIONS: The two principal themes that emerged from the study were (1)
      concerns about the inadequate number of nursing staff and (2) increasing demands
      on the staff for service. Unless addressed successfully, these two issues can
      compromise optimal patient care and add to the cost of health care. IMPLICATIONS
      FOR NURSING MANAGEMENT: There is an urgent need to improve the management of
      nurses' workloads and to communicate better with frontline nursing staff on
      issues such as payment and employee benefits, the number of staff on duty and
      continuing nursing education.

PMID- 22591152
TI  - Predicting nurses' well-being from job demands and resources: a cross-sectional
      study of emotional labour.
AB  - AIM: The aim of the present study was to investigate the effects of job demands
      and resources as well as emotional labour on job satisfaction and emotional
      exhaustion among nurses. BACKGROUND: While emotional labour is a construct that
      has considerable significance in health care as nurses often need to express
      organizationally desired emotions, little research has investigated the
      relationships between emotional labour, job demands and resources in the
      prediction of nurses' well-being. METHODS: The questionnaire was distributed to
      450 registered nurses (RN) working in a teaching hospital in Taiwan during
      February 2007, of which 240 valid questionnaires were returned and analysed
      (53.33% response rate). In addition to descriptive statistics and correlation,
      structural equation modelling (LISREL 8.8) was conducted. RESULTS: The findings
      showed that the frequency of interacting with difficult patients positively
      related to surface acting. Perceived organizational support (POS) positively
      related to deep acting and negatively to surface acting. The results also showed
      that surface acting related negatively, and deep acting related positively, to
      job satisfaction. The frequency of interactions with difficult patients related
      positively to emotional exhaustion, and negatively to job satisfaction. Perceived
      organizational support related negatively to emotional exhaustion and positively
      to job satisfaction. CONCLUSIONS: The results suggest that job demands, resources
      and emotional labour can predict nurses' well-being. IMPLICATIONS FOR NURSING
      MANAGEMENT: The results of the present study indicate that nurses' well-being can
      be predicted by job demands, resources and emotional labour. There is a need to
      address organizational support and training programmes to enhance job
      satisfaction and reduce emotional exhaustion among nurses.

PMID- 22591153
TI  - Mediating the effects of work-life conflict between transformational leadership
      and health-care workers' job satisfaction and psychological wellbeing.
AB  - AIM: To explore the mediating effects of work-life conflict between
      transformational leadership and job satisfaction and psychological wellbeing.
      BACKGROUND: The importance of work-life balance for job satisfaction and
      wellbeing among health-care employees is well-recognized. Evidence shows that
      transformational leadership style is linked to psychological wellbeing. It is
      possible that transformational leadership is also associated with employees'
      perceptions of work-life conflict, thereby influencing their job satisfaction and
      wellbeing. METHODS: A longitudinal design was used where staff working within
      Danish elderly care completed a questionnaire at baseline and 18-month follow-up
      (N=188). RESULTS: Regression analyses showed that transformational leadership
      style was directly associated with perceptions of work-life conflict, job
      satisfaction and psychological wellbeing. Work-life conflict mediated between
      transformational leadership and wellbeing, but not job satisfaction. CONCLUSION:
      The findings suggest transformational leadership style may improve perceptions of
      work-life balance and employee wellbeing. IMPLICATIONS FOR NURSING MANAGEMENT:
      Managers should adopt transformational leadership styles to reduce work-life
      conflict and enhance the wellbeing of their staff.

PMID- 22591154
TI  - Job satisfaction among Iranian hospital-based practicing nurses: examining the
      influence of self-expectation, social interaction and organisational situations.
AB  - AIM: The influence of self-expectation, social interaction, and organisational
      situation on job satisfaction among nurses is examined. BACKGROUND: Understanding
      determinants and correlates of job satisfaction are important factors that help
      to reduce the problem of nurse attrition. METHODS: Utilizing the Hybrid Model of
      concept development, job satisfaction was examined in three phases: (1) the
      theoretical phase, a working definition and the dimensions of job satisfaction
      were established; (2) the fieldwork phase, a qualitative semi-structured
      interview was employed to capture participants' perceptions of the concept; and
      (3) the analytical phase, the experiences of nurses were evaluated using the
      conceptual model. RESULTS: The results indicate that personal beliefs, rather
      than social interaction or organisational situation, constitute the core of job
      satisfaction. CONCLUSIONS: Despite the variety of dissatisfaction factors rooted
      in social interaction and organisational situation, participants achieved the
      highest job satisfaction when trusting in self-value systems and the spiritual
      value of their job objectives. IMPLICATIONS: Intervention is needed to increase
      organisational and professional support for nurses. However, highlighting the
      sacred and spiritual value of the nursing profession, which is rooted in
      religious values and culture, provides additional reinforcement for enhancing the
      job satisfaction among this segment of health care providers.

PMID- 22591155
TI  - The migration and transitioning experiences of internationally educated nurses: a
      global perspective.
AB  - AIM: To comprehensively review recent literature related to the migration and
      transitioning experiences of internationally educated nurses (IENs). BACKGROUND:
      Many developed nations are redressing nursing deficits by recruiting IENs.
      Acquiring credentialing is historically recognized as a barrier to obtaining
      meaningful employment, yet broader issues of transition into global health care
      contexts are also significant. METHODS: A database search of CINAHL, Medline,
      Scopus and Web of Science, and a hand-search of key nursing journals produced 239
      combined hits, with 21 articles meeting the inclusion criteria. RESULTS: Five
      common themes were extracted and synthesized including: (1) reasons for and
      challenges with immigration, (2) cultural displacement, (3) credentialing
      difficulties and 'deskilling', (4) discriminatory experiences and (5) strategies
      of IENs which smoothed transition. CONCLUSIONS: Although major reasons for
      migration are related to improved income and professional stature, these have
      overwhelmingly shown to erode upon relocation. Cultural displacement appears to
      largely stem from communication and language differences, feelings of being an
      outsider and differences in nursing practice. The deskilling process and
      discrimination are also key players which hinder transition and demoralize many
      IENs. IMPLICATIONS FOR NURSING MANAGEMENT: The present study highlights that the
      huge advantages in professional skill and cultural diversity that IENs can bring
      to any nursing unit will not be fully realized without substantial efforts to
      reduce practice limitations (deskilling) and discrimination. Individual
      strategies for easing the transition should be taught to IENs, probably through
      mentorship by experienced IENs.

PMID- 22591156
TI  - Iranian nurses self-perception -- factors influencing nursing image.
AB  - AIM: The purpose of this study was to describe the perspectives of Iranian nurses
      regarding factors influencing nursing image. BACKGROUND: Nursing image is closely
      tied to the nurse's role and identity, influencing clinical performance, job
      satisfaction and quality of care. Images of nursing and nurses are closely linked
      to the cultural context in which nursing is practised, hence, this study explores
      how Iranian nurses perceive the factors that influence their own image. METHODS:
      A descriptive study using a survey design was conducted with 220 baccalaureate
      qualified nurses working in four teaching hospitals in an urban area of Iran. A
      Nursing Image Questionnaire was used and analysed using descriptive and
      inferential statistics. RESULTS: In the domains of 'characteristics required for
      entry to work', 'social role characteristics of nursing' and 'prestige, economic
      and social status, and self image' the nurses had negative images. 'Reward' and
      'opportunity for creativity and originality' were factors that least influenced
      choosing nursing as a career. The presence of a nurse in the family and working
      in the hospital had the greatest impact on the establishment of nurses' nursing
      image. CONCLUSION: Improving the nursing profession's prestige and social
      position as well as providing the opportunity for creativity and originality in
      nursing practice will change the self-image of Iranian nurses, facilitating
      effective and lasting changes in nursing's image. IMPLICATIONS FOR NURSING
      MANAGEMENT: Nurse managers are well-placed to influence nurses' perceptions of
      nursing's image. Given the finding that thinking about leaving a job positively
      correlates with holding a negative nursing image, nurse managers need to consider
      how they can work effectively with their staff to enhance morale and nurses'
      experience of their job.

PMID- 22591157
TI  - More alike than different: a comparison of male and female RNs in rural and
      remote Canada.
AB  - AIM: To explore gender differences and similarities on personal, employment and
      work-life factors and predictors of job satisfaction among registered nurses in
      rural and remote Canada. BACKGROUND: Research suggests that men and women are
      attracted to nursing for different reasons, with job security, range of
      employment opportunities and wages being important for male nurses. METHODS:
      Using data from a large national survey of registered nurses in rural and remote
      Canada, descriptive and multiple linear regression analyses were used to identify
      gender differences and similarities. RESULTS: A larger proportion of male nurses
      reported experiencing aggression in the workplace. Age, annual gross income and
      colleague support in medicine were not found to be predictors of work
      satisfaction for the male nurses, although they were for women. CONCLUSION: There
      are more similarities than differences between male and female registered nurses
      in factors that affect job satisfaction. IMPLICATIONS FOR NURSING MANAGEMENT:
      Nursing management needs to increase their awareness of the potential for
      workplace aggression towards male registered nurses and to explore the
      perceptions of interpersonal interactions that affect satisfaction in the
      workplace.

PMID- 22591158
TI  - Conflict management and job satisfaction in paediatric hospitals in Greece.
AB  - AIM: To assess the major causes of conflict and to identify choices of strategy
      in handling conflicts. BACKGROUND: Conflict is inherent to hospitals as in all
      complex organizations, and health personnel deal with internal and external
      conflicts daily. METHODS: The sample consisted of 286 participants. A five-part
      questionnaire, specific for conflicts in hospitals, was administered to health
      personnel. RESULTS: Of the participants 37% were physicians and 63% were nurses
      and nursing assistants. As far as choice of strategy in conflict management is
      concerned, avoidance was found to be the most frequent mode chosen while
      accommodation was the least frequent mode. Organizational problems were the main
      issue creating conflicts since 52% of nurses and 45% of physicians agreed that
      receiving direction from more than one manager may lead to conflicts (P=0.02).
      Educational differences and communication gaps were reported as another cause of
      conflicts, with nurses supporting this statement more than the other groups
      (P=0.006). CONCLUSION: To become effective in conflict management nurses and
      physicians must understand causes and strategies in handling conflicts.
      IMPLICATIONS FOR NURSING MANAGEMENT: Major changes are needed regarding human
      resource management, work incentives and dynamics of teamwork in order to improve
      working conditions in Greek public hospitals.

PMID- 22591159
TI  - Cys34 adducts of reactive oxygen species in human serum albumin.
AB  - Long-term exposures to reactive oxygen species (ROS) have been linked to scores
      of chronic diseases. This has motivated interest in oxidation products of the
      only free cysteine residue (Cys34) of human serum albumin (HSA) as possible
      biomarkers of ROS exposure. However, Cys34 oxidation products have not been
      detected in human serum or plasma. Using liquid chromatography-high resolution
      tandem mass spectrometry, we report accurate masses and molecular compositions of
      Cys34 oxidation products in the 2432 Da peptide resulting from tryptic digestion
      of HSA. Peptides containing the expected sulfinic (Cys-SO(2)H) and sulfonic (Cys
      SO(3)H) acids, as well as an adduct representing addition of one oxygen atom and
      loss of two hydrogen atoms, were detected in four archived samples of human
      plasma and one fresh sample of human serum. We speculate that this latter adduct
      is a sulfinamide formed by intramolecular reaction between either the Cys34
      sulfenic acid (Cys-SOH) or sulfinic acid (Cys-SO(2)H) and the adjacent glutamine
      residue (Gln33). All three Cys34 adducts were measured in the five human samples
      with levels decreasing in the order sulfinic acid > (proposed) sulfinamide >
      sulfonic acid. Parallel measurements of a negative control detected only small
      amounts of the Cys34 sulfonic acid and the (proposed) sulfinamide and did not
      detect the sulfinic acid.

PMID- 22591161
TI  - Concurrent validity of self-report measures of eating disorders in adolescents
      with type 1 diabetes.
AB  - AIM: Eating disorder screening tools have not been adequately validated for use
      with adolescents with type 1 diabetes. This study compared the Youth Eating
      Disorder Examination-Questionnaire (YEDE-Q) and the Eating Disorder Inventory-3
      Risk Composite (EDI-3RC) against the child Eating Disorder Examination (chEDE).
      These screening tools were chosen because they broadly assess eating disorder
      psychopathology and have subscales helpful for clinical management. METHODS: In
      this cross-sectional study, 124 adolescents with type 1 diabetes aged 13-18 years
      completed two self-administered questionnaires, the YEDE-Q and the EDI-3RC.
      Cronbach's alpha was used to assess internal consistency of the tools. Fifty-one
      adolescents, randomly selected, participated in the chEDE. Intraclass
      correlations and Spearman's correlations were used to measure concordance of the
      chEDE with the YEDE-Q and EDI-3RC. RESULTS: The YEDE-Q and EDI-3RC demonstrated
      good subscale internal consistency; Cronbach's alpha for YEDE-Q (0.78-0.95) and
      EDI-3RC (0.79-0.94). High levels of concurrent validity with the chEDE were seen
      with both tools. CONCLUSION: Preliminary evidence is provided for the validation
      of the YEDE-Q and EDI-3RC for use in adolescents with type 1 diabetes. The YEDE-Q
      also defines individual disturbed eating behaviours with frequency ratings which
      can be helpful for tailoring early intervention.

PMID- 22591160
TI  - Investigating the potential value of individual parameters of histological
      grading systems in a sheep model of cartilage damage: the Modified Mankin method.
AB  - A total histological grade does not necessarily distinguish between different
      manifestations of cartilage damage or degeneration. An accurate and reliable
      histological assessment method is required to separate normal and pathological
      tissue within a joint during treatment of degenerative joint conditions and to
      sub-classify the latter in meaningful ways. The Modified Mankin method may be
      adaptable for this purpose. We investigated how much detail may be lost by
      assigning one composite score/grade to represent different degenerative
      components of the osteoarthritic condition. We used four ovine injury models
      (sham surgery, anterior cruciate ligament/medial collateral ligament instability,
      simulated anatomic anterior cruciate ligament reconstruction and meniscal
      removal) to induce different degrees and potentially 'types' (mechanisms) of
      osteoarthritis. Articular cartilage was systematically harvested, prepared for
      histological examination and graded in a blinded fashion using a Modified Mankin
      grading method. Results showed that the possible permutations of cartilage damage
      were significant and far more varied than the current intended use that
      histological grading systems allow. Of 1352 cartilage specimens graded, 234
      different manifestations of potential histological damage were observed across 23
      potential individual grades of the Modified Mankin grading method. The results
      presented here show that current composite histological grading may contain
      additional information that could potentially discern different stages or
      mechanisms of cartilage damage and degeneration in a sheep model. This approach
      may be applicable to other grading systems.

PMID- 22591162
TI  - The relation between exposure to sophisticated and complex language and early
      adolescent English-only and language minority learners' vocabulary.
AB  - This study investigated the relation between teachers' (N = 22) use of
      sophisticated and complex language in urban middle-school classrooms and their
      students' (mean age at pretest = 11.51 years; N = 782; 568 language minority and
      247 English only) vocabulary knowledge. Using videotaped classroom observations,
      teachers' speech was transcribed and coded for their total amount of talk,
      vocabulary usage, and syntactic complexity. Students' vocabulary skills were
      assessed at the beginning and end of the school year. Results showed variation in
      students' vocabulary skills and teachers' language use. Hierarchical linear
      modeling techniques revealed that after controlling for classroom and school
      composition and students' beginning-of-the-year scores, students' end-of-the-year
      vocabulary skills were positively related to teachers' use of sophisticated
      vocabulary and complex syntax, but not teachers' total amount of talk.

PMID- 22591164
TI  - Reaction of methacrolein with the hydroxyl radical in air: incorporation of
      secondary O2 addition into the MACR + OH master equation.
AB  - Methacrolein (MACR) plays an important role in atmospheric chemistry within the
      planetary boundary layer, as it is one of the major oxidation products of
      isoprene and has a short lifetime toward the hydroxyl radical (OH). In this
      study, quantum chemical techniques and statistical reaction rate theory have been
      used to simulate the addition of OH to MACR at conditions representative of the
      troposphere. In this chemically activated reaction, the time scales for product
      formation versus collisional deactivation of the vibrationally excited adduct are
      explicitly considered. Furthermore, the subsequent addition of O(2) is also
      incorporated within a single master equation, so as to investigate doubly
      activated peroxyl radical formation. The major reaction product of OH addition to
      MACR is the HOCH(2)C(*)(CH(3))CHO radical formed via addition to the outer (beta)
      carbon. This radical is predominantly in the Z isomer although around a third of
      the population is quenched as the higher-energy E isomer. Calculated rate
      constants agree well with experiment when using M06-2X/aug-cc-pVTZ barrier
      heights, but are somewhat overpredicted using G3SX energies. The overall rate
      constant is controlled by competition between dissociation of the MACR...OH van
      der Waals complex back to reactants and isomerization on to MACR-OH adducts,
      which takes place on a time scale of several nanoseconds, but collisional
      deactivation of the MACR-OH adducts occurs on a time scale that is around an
      order of magnitude longer. When O(2) addition is included in the master equation,
      we observe that the MACR-OH adducts are removed by reaction with O(2) on a
      similar time scale to collisional deactivation. Around 50% of the subsequent
      peroxyl radical population is formed with some identifiable excess vibrational
      energy above singly activated [MACR-OH-O(2)]*, with around 20% provided with an
      additional 20 kcal mol(-1) (>40 kcal mol(-1) relative to quenched MACR-OH-O(2))
      that can go into further unimolecular reaction. This double activation process is
      expected to lead to some prompt unimolecular decomposition of excited [MACR-OH
      O(2)]** peroxyl radicals to yield products including hydroxyacetone and
      methylglyoxal, regenerating the initiating OH radical in the process.

PMID- 22591163
TI  - GPs' decision-making--perceiving the patient as a person or a disease.
AB  - BACKGROUND: The aim of this study was to analyse the clinical decision making
      strategies of GPs with regard to the whole range of problems encountered in
      everyday work. METHODS: A prospective questionnaire study was carried through,
      where 16 General practitioners in Sweden registered consecutively 378 problems in
      366 patients. RESULTS: 68.3% of the problems were registered as somatic, 5.8% as
      psychosocial and 25.9% as both somatic and psychosocial. When the problem was
      characterised as somatic the main emphasis was most often on the symptoms only,
      and when the problem was psychosocial main emphasis was given to the person.
      Immediate, inductive, decision-making contrary to gradual, analytical, was used
      for about half of the problems. Immediate decision-making was less often used
      when problems were registered as both somatic and psychosocial and focus was on
      both the symptoms and the person. When immediate decision-making was used the GPs
      were significantly more often certain of their identification of the problem and
      significantly more satisfied with their consultation. Rules of thumb in
      consultations registered as somatic with emphasis on symptoms only did not
      include any reference to the individual patient. In consultations registered as
      psychosocial with emphasis on the person, rules of thumb often included reference
      to the patient as a known person. CONCLUSIONS: The decision-making (immediate or
      gradual) registered by the GPs seemed to have been adjusted on the symptom or on
      the patient as a person. Our results indicate that the GPs seem to recognise
      immediately both problems and persons, hence the quintessence of the expert skill
      of the GP as developed through experience.

PMID- 22591165
TI  - Voltage-gated potassium channel (K(v) 1) autoantibodies in patients with chagasic
      gut dysmotility and distribution of K(v) 1 channels in human enteric
      neuromusculature (autoantibodies in GI dysmotility).
AB  - BACKGROUND: Autoantibodies directed against specific neuronal antigens are found
      in a significant number of patients with gastrointestinal neuromuscular diseases
      (GINMDs) secondary to neoplasia. This study examined the presence of antineuronal
      antibodies in idiopathic GINMD and GINMD secondary to South American
      Trypanosomiasis. The GI distribution of voltage-gated potassium channels (VGKCs)
      was also investigated. METHODS: Seventy-three patients were included in the study
      with diagnoses of primary achalasia, enteric dysmotility, chronic intestinal
      pseudo-obstruction, esophageal or colonic dysmotility secondary to Chagas'
      disease. Sera were screened for specific antibodies to glutamic acid
      decarboxylase, voltage-gated calcium channels (VGCCs; P/Q subtype), nicotinic
      acetylcholine receptors (nAChRs; alpha3 subtype), and voltage-gated potassium
      channels (VGKCs, K(V) 1 subtype) using validated immunoprecipitation assays. The
      distribution of six VGKC subunits (K(V) 1.1-1.6), including those known to be
      antigenic targets of anti-VGKC antibodies was immunohistochemically investigated
      in all main human GI tract regions. KEY RESULTS: Three patients (14%) with
      chagasic GI dysmotility were found to have positive anti-VGKC antibody titers. No
      antibodies were detected in patients with idiopathic GINMD. The VGKCs were found
      in enteric neurons at every level of the gut in unique yet overlapping
      distributions. The VGKC expression in GI smooth muscle was found to be limited to
      the esophagus. CONCLUSIONS & INFERENCES: A small proportion of patients with GI
      dysfunction secondary to Chagas' disease have antibodies against VGKCs. The
      presence of these channels in the human enteric nervous system may have
      pathological relevance to the growing number of GINMDs with which anti-VGKC
      antibodies have been associated.

PMID- 22591166
TI  - Efficient catalytic reduction of hexavalent chromium using palladium nanoparticle
      immobilized electrospun polymer nanofibers.
AB  - We report a facile and economic approach to fabricating catalytic active
      palladium (Pd) nanoparticle (NP)-immobilized electrospun polyethyleneimine
      (PEI)/polyvinyl alcohol (PVA) nanofibers for catalytic reduction of hexavalent
      chromium (Cr(VI)) to trivalent chromium (Cr(III)). In this study, PEI/PVA
      nanofibrous mats were first electrospun from homogeneous mixture solution of PEI
      and PVA, followed by cross-linking with glutaraldehyde vapor to render the fibers
      with good water stability. The nanofibrous mats were then alternatively soaked in
      potassium tetrachloropallidate (K2PdCl4) and sodium borohydride solution, and the
      PdCl4(2-) anions complexed with the free amine groups of PEI were able to be
      reduced to form zero-valent Pd NPs. The formed Pd NP-containing PEI/PVA
      nanofibers were characterized by different techniques. We show that the
      immobilization of Pd NPs does not significantly change the morphology of the
      PEI/PVA nanofibers; instead the mechanical durability of the fibers is
      significantly improved. The formed Pd NPs with a mean diameter of 2.6 nm are
      quite uniformly distributed within the fibers with a small portion of particles
      having a denser distribution at the outer surface of the fibers. The catalytic
      activity and reusability of the fabricated Pd NP-containing fibrous mats were
      evaluated by transformation of Cr(VI) to Cr(III) in aqueous solution in the
      presence of a reducing agent. Our results reveal that the Pd NP-containing
      nanofibrous mats display an excellent catalytic activity and reusability for the
      reduction of Cr(VI) to Cr(III). The facile approach to fabricating metal NP
      immobilized polymer nanofibers with a high surface area to volume ratio, enhanced
      mechanical durability, and uniform NP distribution may be extended to prepare
      different NP-immobilized fibrous systems for various applications in catalysis,
      sensing, environmental sciences, and biomedicine. 

PMID- 22591167
TI  - PXR ligand classification model with SFED-weighted WHIM and CoMMA descriptors.
AB  - Understanding which type of endogenous and exogenous compounds serve as agonists
      for the nuclear pregnane X receptor (PXR) would be valuable for drug discovery
      and development, because PXR regulates a large number of genes related to
      xenobiotic metabolism. Although several models have been proposed to classify
      human PXR activators and non-activators, models with better predictability are
      necessary for practical purposes in drug discovery. Grid-weighted holistic
      invariant molecular (G-WHIM) and comparative molecular moment analysis (G-CoMMA)
      type 3D descriptors that contain information about the solvation free energy of
      target molecules were developed. With these descriptors, prediction models built
      using decision tree (DT)-, support vector machine (SVM)-, and Kohonen neural
      network (KNN)-based models exhibited better predictability than previously
      proposed models. Solvation free energy density-weighted G-WHIM and G-CoMMA
      descriptors reveal new insights into PXR ligand classification, and incorporation
      with machine learning methods (DT, SVM, KNN) exhibits promising results,
      especially SVM and KNN. SVM- and KNN-based models exhibit accuracy around 0.90,
      and DT-based models exhibit accuracy around 0.8 for both the training and test
      sets.

PMID- 22591168
TI  - Magnitude of the problem of drinking alcohol on college campuses, commentary on
      "Structuring a college alcohol prevention program on the low level of response to
      alcohol model: a pilot model".
AB  - BACKGROUND: The objective of this commentary is to discuss the significance of
      the study entitled, "Structuring a College Alcohol Prevention Program on the Low
      Level of Response to Alcohol Model: A Pilot Model" by Schuckit and colleagues
      (2012) published in this issue of the Alcoholism: Clinical and Experimental
      Research. The work by Schuckit and colleagues emphasizes the importance of
      personalizing an alcohol prevention program for college students. METHODS: This
      pilot model is the result of over 30 years of clinical translational research on
      an individual's level of response to alcohol. The prevention program is
      efficient, simple, safe, cost-effective and self-directed. RESULTS: The results
      indicate the computerized intervention was associated with decreases in drinking
      overall and students with a low level of response to alcohol showed greater
      decreases when the prevention program is personalized to focus on how level of
      response is affected by peer influence, alcohol expectancies, and stress
      management. It concludes that college students with a low level of response to
      alcohol will benefit from a prevention program that is personalized to this well
      documented endophenotype. CONCLUSIONS: The findings provide the foundation for
      developing future longitudinal studies of the proposed prevention program with a
      larger sample size on diverse campuses. In addition, as mentioned in the
      Discussion section, future studies could also evaluate the effectiveness of other
      easily measured clinical endophenotypes known to be associated with alcohol use
      such as impulsivity, negative effect, and maximum number of drinks per occasion.

PMID- 22591169
TI  - The 2010 IADR--Geriatric Oral Research Group satellite meeting.
AB  - On 12 and 13 July, the 2010 IADR General Session satellite meeting of the IADR -
      Geriatric Oral Research Group (GORG) - was attended by around 60 participants in
      the beautiful surroundings of Sitges in the outskirts of Barcelona, Spain. The
      speakers reflected on the main topics 'Disparities and Expectations in Oral
      Healthcare: An Elderly Focus' and 'Risks and Benefits of Ageing with a Natural
      Dentition', which was followed by fruitful discussions in the auditorium and the
      jointly enjoyed meals. The Sitges meeting comprised lectures of distinguished
      speakers as well as poster presentations, which discussed and defined the
      situation of research in the field of gerodontology today as well as the
      development since the last GORG satellite symposium held on Vancouver Island in
      1999. Despite enormous progress over the last 10 years, many important questions
      concerning economics, regulation, the implementation of oral health care,
      treatment protocols as well as general health implications of oral disease in the
      frail and elderly remain still unanswered.

PMID- 22591170
TI  - Evaluation of the leukocyte differential on a new automated flow cytometry
      hematology analyzer.
AB  - INTRODUCTION: The Hematoflow (Beckman Coulter, USA) is a new automated hematology
      analyzer, which provides a 16-part white blood cell count (WBC) differential.
      METHODS: We evaluated the differential WBC count performance of the Hematoflow.
      101 blood samples from patients were selected for comparison analysis. RESULTS:
      The methodological comparison of the WBC differential parameters of neutrophils,
      lymphocytes, monocytes and eosinophils showed good correlations among 4 different
      analyses. More than 1% of blast cells were counted in 30 of 101 samples. A good
      correlation for blast cell counts obtained by Hematoflow was found with the
      reference manual method (r=0.9637, P 0.0001). For blast B, Hematoflow shows good
      correlation with reference method results but did not identify blast T.
      CONCLUSIONS: These results demonstrate that the Hematoflow has a comparable
      performance with the Sysmex XE-2100 and indicate that B cell lineage ALL can be
      identified by the use of the Hematoflow in an initial evaluation of acute
      leukemia.

PMID- 22591171
TI  - Observation of the inverse trans influence (ITI) in a uranium(V) imide
      coordination complex: an experimental study and theoretical evaluation.
AB  - An inverse trans influence has been observed in a high-valent U(V) imide complex,
      [(((Ad)ArO)(3)N)U(NMes)]. A thorough theoretical evaluation has been employed in
      order to corroborate the ITI in this unusual complex. Computations on the target
      complex, [(((Ad)ArO)(3)N)U(NMes)], and the model complexes
      [(((Me)ArO)(3)N)U(NMes)] and [(NMe(3))(OMe(2))(OMe)(3)U(NPh)] are discussed along
      with synthetic details and supporting spectroscopic data. Additionally, the
      syntheses and full characterization data of the related U(V) trimethylsilylimide
      complex [(((Ad)ArO)(3)N)U(NTMS)] and U(IV) azide complex [(((Ad)ArO)(3)N)U(N(3))]
      are also presented for comparison.

PMID- 22591172
TI  - Health status and behaviors among adults residing in rural Dominican Republic.
AB  - INTRODUCTION: The rapidly increasing burden of chronic diseases linked to
      adequacy of healthcare services and individual health behaviors is a key
      determinant of global public health. Given demographic aging and the accompanying
      health transition, chronic diseases in low and middle income communities of the
      Dominican Republic are likely to increase significantly. The objective of this
      article was to report on efforts in surveillance of health conditions and
      behaviors in underserved rural Dominican communities. METHODS: A modified 30
      item, language-sensitive health survey was randomly administered to 117 adult
      participants (18 years and older) during a health fair held at three rural
      villages from March to April 2009 in the rural San Cristobal region of the
      Dominican Republic. Descriptive analyses of select health conditions and behavior
      variables from all completed surveys were tabulated. RESULTS: Adult participant
      ages ranged from 18 to 79 years (mean +/- standard deviation; 34.0 +/- 2.1),
      height from 1.4 to 2.0 m (1.7 +/- 0.1), weight from 41.8 to 100.0 kg (66.2 +/-
      1.7) and BMI from 15.2 to 46.2 (24.2 +/- 0.7). Overall, 69.2% of the sample self
      reported their general health status to be fair to poor. The top three chronic
      diseases included: high blood pressure (35.8%), diabetes (15.0%), and asthma
      (14.2%). In all, 33.4% reported current smoker status and 61.7% were classified
      as heavy alcohol drinkers. CONCLUSION: Considerable variation was found in the
      self-report of health conditions and behavioral characteristics among those
      individuals that attended the health fair. Documenting these important health
      indicators in the rural communities has the potential to inform the development
      of surveillance activities and prevention efforts for future health education
      interventions.

PMID- 22591173
TI  - Thermodynamics of Zn2+ binding to Cys2His2 and Cys2HisCys zinc fingers and a Cys4
      transcription factor site.
AB  - The thermodynamics of Zn(2+) binding to three peptides corresponding to naturally
      occurring Zn-binding sequences in transcription factors have been quantified with
      isothermal titration calorimetry (ITC). These peptides, the third zinc finger of
      Sp1 (Sp1-3), the second zinc finger of myelin transcription factor 1 (MyT1-2),
      and the second Zn-binding sequence of the DNA-binding domain of glucocorticoid
      receptor (GR-2), bind Zn(2+) with Cys(2)His(2), Cys(2)HisCys, and Cys(4)
      coordination, respectively. Circular dichroism confirms that Sp1-3 and MyT1-2
      have considerable and negligible Zn-stabilized secondary structure, respectively,
      and indicate only a small amount for GR-2. The pK(a)'s of the Sp1-3 cysteines and
      histidines were determined by NMR and used to estimate the number of protons
      displaced by Zn(2+) at pH 7.4. ITC was also used to determine this number, and
      the two methods agree. Subtraction of buffer contributions to the calorimetric
      data reveals that all three peptides have a similar affinity for Zn(2+), which
      has equal enthalpy and entropy components for Sp1-3 but is more enthalpically
      disfavored and entropically favored with increasing Cys ligands. The resulting
      enthalpy-entropy compensation originates from the Zn-Cys coordination, as
      subtraction of the cysteine deprotonation enthalpy results in a similar Zn(2+)
      binding enthalpy for all three peptides, and the binding entropy tracks with the
      number of displaced protons. Metal and protein components of the binding enthalpy
      and entropy have been estimated. While dominated by Zn(2+) coordination to the
      cysteines and histidines, other residues in the sequence affect the protein
      contributions that modulate the stability of these motifs.

PMID- 22591174
TI  - Segmentation and tracking of live cells in phase-contrast images using
      directional gradient vector flow for snakes.
AB  - Cell shape is an important characteristic of the physiological state of a cell
      and is used as a primary read-out of cell behaviour in various assays. Automated
      accurate segmentation of cells in microscopy images is hence of large practical
      importance in cell biology. We report a simple algorithm for automated cell
      segmentation in high-magnification phase-contrast images, which takes advantage
      of the characteristic directionality of the local image intensity gradient at
      cellular boundaries due to the 'halo-effect'. We employ a two-step algorithm in
      which a gradient vector flow (GVF) field is first used to direct active contours
      to an approximate cell boundary. A directional GVF (DGVF) field is then
      calculated by considering only edges for which the image intensity gradient is
      directed outwards with respect to the approximate cell contour. Subsequently, the
      DGVF field is used to refine the cell contour, by directing active contours to
      edges with the desired gradient directionality. This method allows us to
      accurately segment cells in an image series, as well as follow the dynamics of
      cell shape over time in an automated fashion.

PMID- 22591175
TI  - Improvement in solubility and bioavailability of puerarin by mechanochemical
      preparation.
AB  - An efficient and solvent-free procedure was developed to improve the solubility
      and bioavailability of the poorly water-soluble drug puerarin by mechanochemical
      technology. The stable inclusion complex of puerarin and 2-hydroxypropyl-beta
      cyclodextrin (HPCD) was prepared by a ball mill under the following conditions:
      equimolar ratio of puerarin to HPCD; rotational speed of 250 rpm; milling time of
      90 min; steel balls of 22 mm diameter. The solid complex was characterized by
      scanning electron microscopy (SEM), differential scanning calorimetry (DSC),
      powder X-ray diffractometry (XRD), and fourier transformation-infrared
      spectroscopy (FT-IR). Mechanochemical action could result in enhanced molecular
      encapsulation, homogeneous distribution and amorphization of the drug. In
      comparison to puerarin, a 1.64-fold increase in absolute bioavailability was
      obtained. The solubility of the inclusion complex was 25.33-fold higher and the
      drug release amount reached 79.44% at 15 min, 2.76-fold higher.

PMID- 22591177
TI  - Negative impact of FLT3-ITD mutation on expression of MDR-1 mRNA in adult acute
      myeloid leukemia.

PMID- 22591178
TI  - Role in metal homeostasis of CtpD, a Co2+ transporting P(1B4)-ATPase of
      Mycobacterium smegmatis.
AB  - Genetic studies in the tuberculosis mouse model have suggested that mycobacterial
      metal efflux systems, such as the P(1B4)-ATPase CtpD, are important for
      pathogenesis. The specificity for substrate metals largely determines the
      function of these ATPases; however, various substrates have been reported for
      bacterial and plant P(1B4)-ATPases leaving their function uncertain. Here we
      describe the functional role of the CtpD protein of Mycobacterium smegmatis. An
      M. smegmatis mutant strain lacking the ctpD gene was hypersensitive to Co2+ and
      Ni2+ and accumulated these metals in the cytoplasm. ctpD transcription was
      induced by both Co2+ and superoxide stress. Biochemical characterization of
      heterologously expressed, affinity-purified CtpD showed that this ATPase is
      activated by Co2+, Ni2+ and to a lesser extend Zn2+ (20% of maximum activity).
      The protein was also able to bind one Co2+, Ni2+ or Zn2+ to its transmembrane
      transport site. These observations indicate that CtpD is important for Co2+ and
      Ni2+ homeostasis in M. smegmatis, and that M. tuberculosis CtpD orthologue could
      be involved in metal detoxification and resisting cellular oxidative stress by
      modulating the intracellular concentration of these metals.

PMID- 22591179
TI  - Necrotizing pneumonia caused by nanC-carrying serotypes is associated with
      pneumococcal haemolytic uraemic syndrome in children.
AB  - Streptococcus pneumoniae infection is a leading cause of morbidity and mortality
      worldwide. One of the most severe complications of invasive pneumococcal disease
      (IPD) is haemolytic uraemic syndrome (HUS). This study was undertaken to
      determine the risk factors and role of pneumococcal neuraminidases in HUS in
      children with IPD. Eighteen cases of HUS and 54 patients with IPD without HUS
      were identified. The controls were patients with culture-confirmed IPD without
      HUS. Clinical and laboratory characteristics of the two groups of patients were
      compared. Bacterial isolates from both groups were serotyped, sequence typed and
      examined for their carriage of three neuraminidase genes. Necrotizing pneumonia
      and serotype 3 infection were significantly associated with HUS in children with
      IPD, suggesting that a severe pulmonary suppurating disease increase the risk of
      HUS. Serotype 14 was associated with necrotizing pneumonia but not HUS. Children
      with HUS were more likely to require surgery and had a longer duration of
      hospitalization. The study identified a significantly higher carriage of a
      neuraminidase gene, nanC, in the causative pneumococcal isolates from patients
      with HUS (89% versus 41%, p 0.001). The sensitivity and specificity of nanC to
      predict HUS were 89% and 59%, respectively. In conclusion, necrotizing pneumonia,
      serotype 3 infection and neuraminidase gene nanC were associated with HUS in
      children with IPD. The result suggests that NanC could provide an additive effect
      to NanA and NanB in the overall activity of pneumococcal neuraminidases to expose
      Thomsen-Friedenreich antigen on various cells in patients with HUS.

PMID- 22591180
TI  - Emotion regulation in the context of frustration in children with high
      functioning autism and their typical peers.
AB  - BACKGROUND: It is well accepted that emotion regulation difficulties are a
      serious concern for children with ASD, yet empirical studies of this construct
      are limited for this population. The present study describes group differences
      between high functioning children with autism and their typical peers in
      frustration and discrete coping strategies for emotion regulation. We also use
      sequential analyses to test differences in the efficacy of individual coping
      strategies at regulating children's frustration. METHODS: Subjects were 20
      children with autism (M = 59 months) and 20 developmentally matched typically
      developing children (M = 50 months). Measures of children's frustration (negative
      facial expressions and behaviors, negative vocalizations, resignation) and
      emotion regulation coping strategies were observationally coded from structured
      video recordings. RESULTS: Children with autism displayed a higher intensity and
      duration of resignation, and the group difference became most pronounced when
      children worked alone during the parent-absent segment of the locked box task.
      Children with autism used significantly more avoidance and venting strategies,
      and fewer constructive strategies than typical children. Sequential analyses
      revealed that social support strategies (orienting and verbalizing to the
      experimenter) were ineffective for children with autism, while these behaviors,
      vocal venting, and distraction strategies were all effective for typically
      developing children. CONCLUSIONS: The results go beyond the recent literature by
      offering a rich description of children's efforts to regulate their frustration
      when faced with challenge, and point to important contextual differences in the
      efficacy of children's coping strategies.

PMID- 22591181
TI  - The evolution of alternative developmental pathways: footprints of selection on
      life-history traits in a butterfly.
AB  - Developmental pathways may evolve to optimize alternative phenotypes across
      environments. However, the maintenance of such adaptive plasticity under relaxed
      selection has received little study. We compare the expression of life-history
      traits across two developmental pathways in two populations of the butterfly
      Pararge aegeria where both populations express a diapause pathway but one never
      expresses direct development in nature. In the population with ongoing selection
      on both pathways, the difference between pathways in development time and growth
      rate was larger, whereas the difference in body size was smaller compared with
      the population experiencing relaxed selection on one pathway. This indicates that
      relaxed selection on the direct pathway has allowed life-history traits to drift
      towards values associated with lower fitness when following this pathway. Relaxed
      selection on direct development was also associated with a higher degree of
      genetic variation for protandry expressed as within-family sexual dimorphism in
      growth rate. Genetic correlations for larval growth rate across sexes and
      pathways were generally positive, with the notable exception of correlation
      estimates that involved directly developing males of the population that
      experienced relaxed selection on this pathway. We conclude that relaxed selection
      on one developmental pathway appears to have partly disrupted the developmental
      regulation of life-history trait expression. This in turn suggests that ongoing
      selection may be responsible for maintaining adaptive developmental regulation
      along alternative developmental pathways in these populations.

PMID- 22591182
TI  - Contribution of temporal processing skills to reading comprehension in 8-year
      olds: evidence for a mediation effect of phonological awareness.
AB  - This study tested whether the association between temporal processing (TP) and
      reading is mediated by phonological awareness (PA) in a normative sample of 615
      eight-year-olds. TP was measured with auditory and bimodal (visual-auditory)
      temporal order judgment tasks and PA with a phoneme deletion task. PA partially
      mediated the association between both auditory and bimodal TP and reading, above
      nonverbal abilities, vocabulary, and processing speed. PA explained a larger
      proportion of the association between auditory TP and reading (56% vs. 39% for
      bimodal TP), and most of the association between bimodal TP and reading was
      direct. This finding is consistent with a dual-phonological and visual-pathway
      model of the association between TP and reading in normative reading skills.

PMID- 22591183
TI  - Structural alterations of the mucosa stroma in the Barrett's esophagus metaplasia
      dysplasia-adenocarcinoma sequence.
AB  - BACKGROUND AND AIM: Accumulating evidence suggests that the extracellular matrix
      play important roles in intercellular communications and contribute to the
      development of a number of diseases, including diseases of the gastrointestinal
      tract. The present study examined the structural characteristics and alterations
      of the extracellular matrix of the mucosa stroma in the Barrett's esophagus
      metaplasia-dysplasia-adenocarcinoma sequence. METHODS: A total of 41 esophageal
      tissue specimens (15 esophageal adenocarcinoma, 10 Barrett's esophagus intestinal
      metaplasia, seven dysplasia and nine normal esophagus) were studied. The present
      study used transmission electron microscopy and computerized quantitative
      electron-microscopic analysis in order to investigate the characteristics of the
      extracellular matrix of the mucosa. RESULTS: The study revealed that marked
      structural alterations of the mucosa stroma, relating to changes in the
      distribution and appearance of collagen fibers as well as to changes in numbers
      of matrix microvesicles, occur in Barrett's esophagus and esophageal
      adenocarcinoma. It was found that there were 3.1 times more microvesicles in the
      stroma in Barrett's esophagus than in the stroma of the normal esophagus
      (P<0.0001) and that there were 5.8 times more microvesicles in esophageal
      adenocarcinoma than in the normal esophagus (P<0.0001). There were 1.9 times more
      microvesicles in esophageal adenocarcinoma than in Barrett's esophagus
      (P=0.0043). CONCLUSIONS: The study demonstrates distinctive alterations of the
      mucosa stroma extracellular matrix in the metaplasia-dysplasia-adenocarcinoma
      sequence. The findings suggest that the redistribution of collagen fibers and
      increases in numbers of matrix microvesicles may play roles in the formation of
      specialized intestinal metaplasia and the development of adenocarcinoma.

PMID- 22591184
TI  - Soluble CD163, a marker of Kupffer cell activation, is related to portal
      hypertension in patients with liver cirrhosis.
AB  - BACKGROUND: Activation of Kupffer cells may be involved in the pathogenesis of
      portal hypertension by release of vasoconstrictive substances and fibrosis due to
      co-activation of hepatic stellate cells. AIM: To study soluble plasma (s) CD163,
      a specific marker of activated macrophages, as a biomarker for portal
      hypertension in patients with liver cirrhosis. METHODS: We measured sCD163
      concentration and the hepatic venous pressure gradient (HVPG) by liver vein
      catheterisation in 81 cirrhosis patients (Child-Pugh CP-A: n = 26, CP-B: n = 29,
      CP-C: n = 26) and 22 healthy subjects. We also measured their cardiac output
      (CO), cardiac index and systemic vascular resistance (SVR). Liver status was
      examined by Child-Pugh and MELD-score. RESULTS: In cirrhosis, sCD163
      concentration was nearly three times higher than in controls (4.7 +/- 2.5 vs. 1.6
      +/- 0.5 mg/L, P < 0.001). sCD163 was also higher, as measured in steps by CP
      score (P < 0.001). The HVPG rose steeply to an asymptote of 22 mmHg with sCD163
      up to about 5 mg/L and not to higher values with higher sCD163. In a multivariate
      analysis, sCD163 was the only independent predictor of the HVPG but did not
      predict any of the systemic circulatory findings. sCD163 > 3.95 mg/L (upper
      normal limit) predicted HVPG >= 10 mmHg with a positive predictive value of 0.99.
      CONCLUSIONS: Circulating sCD163 originating from activated Kupffer cells is
      increased in cirrhosis with increasing Child-Pugh score and with increasing HVPG,
      and it is an independent predictor for HVPG. These findings support a primary
      role of macrophage activation in portal hypertension, and may indicate a target
      for biological intervention.

PMID- 22591185
TI  - Concentration effects and ion properties controlling the fractionation of halides
      during aerosol formation.
AB  - During the aerosolization process at the sea surface, halides are incorporated
      into aerosol droplets, where they may play an important role in tropospheric
      ozone chemistry. Although this process may significantly contribute to the
      formation of reactive gas phase molecular halogens, little is known about the
      environmental factors that control how halides selectively accumulate at the air
      water interface. In this study, the production of sea spray aerosol is simulated
      using electrospray ionization (ESI) of 100 nM equimolar solutions of NaCl, NaBr,
      NaI, NaNO(2), NaNO(3), NaClO(4), and NaIO(4). The microdroplets generated are
      analyzed by mass spectrometry to study the comparative enrichment of anions (f(X(
      ))) and their correlation with ion properties. Although no correlation exists
      between f(X(-)) and the limiting equivalent ionic conductivity, the correlation
      coefficient of the linear fit with the size of the anions R(X(-)), dehydration
      free-energy DeltaG(dehyd), and polarizability alpha, follows the order: R(X(-))(
      2) > R(X(-))(-1) > R(X(-)) > DeltaG(dehyd) > alpha. The same pure physical
      process is observed in H(2)O and D(2)O. The factor f(X(-)) does not change with
      pH (6.8-8.6), counterion (Li(+), Na(+), K(+), and Cs(+)) substitution effects, or
      solvent polarity changes in methanol- and ethanol-water mixtures (0 <= x(H(2)O)
      <= 1). Sodium polysorbate 20 surfactant is used to modify the structure of the
      interface. Despite the observed enrichment of I(-) on the air-water interface of
      equimolar solutions, our results of seawater mimic samples agree with a model in
      which the interfacial composition is increasingly enriched in I(-) < Br(-) < Cl(
      ) over the oceanic boundary layer due to concentration effects in sea spray
      aerosol formation.

PMID- 22591186
TI  - Isolation of template effects that control the structure and function of
      nonspherical, biotemplated Pd nanomaterials.
AB  - Advances in nanotechnology have indicated that the passivant and the inorganic
      surface play a pivotal role in controlling the structure/function relationship of
      materials. Beyond standard materials-based methods, bioligands have recently
      demonstrated the production of unique nanomaterial morphologies for application
      under ambient conditions for multiple activities, such as catalysis and
      biosensing. We have recently demonstrated that a biotemplate technique could be
      employed to produce spherical and linear Pd nanostructures in water using a self
      assembling peptide framework. The materials possessed high catalytic reactivity
      that was controlled by the three-dimensional structure of the composite
      materials. To investigate the effect of the peptide template on the reactivity of
      Pd nanostructures, an in depth analysis of the catalytic activity of Pd
      nanostructures fabricated via truncated templates is presented. The new templates
      were designed from portions of the original framework, which demonstrated unique
      synthetic and functionality control. Two different reactions, Stille C-C coupling
      and 4-nitrophenol reduction, were employed to ascertain the effect of template
      structure on the reactivity of synthesized Pd nanomaterials via changes in
      reagent diffusion through the bioscaffold. The results indicate that the peptide
      framework plays an important role and could be used to tune and optimize the
      functionality of the final composite materials for the target application.

PMID- 22591187
TI  - A potential link of oxidative stress and cell cycle regulation for development of
      endometriosis.
AB  - BACKGROUND: The roles of molecular alteration such as genomic instability and
      cell survival are debated aspects of the pathogenesis of endometriosis. To review
      the contemporary literature on potential factors and their signaling pathways
      that support prolonged survival of endometriotic cells. METHODS: This article
      reviews the English-language literature for molecular, pathogenetic, and
      pathophysiological studies on endometriosis. This review is focused on the
      association of hepatocyte nuclear factor (HNF)-1beta with endometriosis. RESULTS:
      The iron-induced oxidative stress plays a fundamental role for the pathogenesis
      of endometriosis. Oxidative stress, secondary to influx of iron during retrograde
      menstruation, modifies lipids and proteins, leading to cell and DNA damage.
      Recent studies demonstrated HNF-1beta overexpression in endometriotic foci. HNF
      1beta increases the survival of endometriotic cells under iron-induced oxidative
      stress conditions possibly through the activation of forkhead box (FOX)
      transcription factors and/or endometriosis-specific expression of microRNAs.
      Endometriotic cells expressing HNF-1beta also display cell cycle checkpoint
      pathways required to survive DNA damaging events. CONCLUSIONS: HNF-1beta in
      endometriosis might be a factor that controls the cell cycle and DNA damage
      checkpoints.

PMID- 22591188
TI  - Nondestructive covalent "grafting-from" of poly(lactide) particles of different
      geometries.
AB  - A nondestructive "grafting-from" method has been developed using poly(lactide)
      (PLA) particles of different shapes as substrates and three hydrophilic monomers
      as grafts. Irregularly shaped particles and spheres of PLA were covalently
      surface functionalized using a versatile method of photoinduced free radical
      polymerization. The preservation of the molecular weight of the PLA particle bulk
      and the retention of the original particle shape confirmed the negligible effect
      of the grafting method. The changes in surface composition were determined by
      FTIR for both spherical and irregular particles and by XPS for the irregular
      particles showing the versatility of the method. Changes in the surface
      morphology of the PLA spherical particles were observed using microscopy
      techniques showing a full surface coverage of one of the grafted monomers. The
      method is applicable to a wide set of grafting monomers and provides a permanent
      alteration of the surface chemistry of the PLA particles creating hydrophilic PLA
      surfaces in addition to creating sites for further modification and drug delivery
      in the biomedical fields. 

PMID- 22591189
TI  - Clinical and temporal patterns of severe pneumonia causing critical illness
      during Hajj.
AB  - BACKGROUND: Pneumonia is a leading cause of hospitalization during Hajj and
      susceptibility and transmission may be exacerbated by extreme spatial and
      temporal crowding. We describe the number and temporal onset, co-morbidities, and
      outcomes of severe pneumonia causing critical illness among pilgrims. METHOD: A
      cohort study of all critically ill Hajj patients, of over 40 nationalities,
      admitted to 15 hospitals in 2 cities in 2009 and 2010. Demographic, clinical, and
      laboratory data, and variables necessary for calculation of the Acute Physiology
      and Chronic Health Evaluation IV scores were collected. RESULTS: There were 452
      patients (64.6% male) who developed critical illness. Pneumonia was the primary
      cause of critical illness in 123 (27.2%) of all intensive care unit (ICU)
      admissions during Hajj. Pneumonia was community (Hajj)-acquired in 66.7%,
      aspiration-related in 25.2%, nosocomial in 3.3%, and tuberculous in 4.9%.
      Pneumonia occurred most commonly in the second week of Hajj, 95 (77.2%) occurred
      between days 5-15 of Hajj, corresponding to the period of most extreme pilgrim
      density. Mechanical ventilation was performed in 69.1%. Median duration of ICU
      stay was 4 (interquartile range [IQR] 1-8) days and duration of ventilation 4
      (IQR 3-6) days. Commonest preexisting co-morbidities included smoking (22.8%),
      diabetes (32.5%), and COPD (17.1%). Short-term mortality (during the 3-week
      period of Hajj) was 19.5%. CONCLUSION: Pneumonia is a major cause of critical
      illness during Hajj and occurs amidst substantial crowding and pilgrim density.
      Increased efforts at prevention for at risk pilgrim prior to Hajj and further
      attention to spatial and physical crowding during Hajj may attenuate this risk.

PMID- 22591190
TI  - Differential effects of moderate alcohol consumption on performance among older
      and younger adults.
AB  - BACKGROUND: Studies exploring differential effects of acute alcohol consumption
      on younger and older adults are lacking within the field of alcohol research,
      especially those using moderate doses. Previous studies addressing this question
      have tended to use complex behavioral tasks too broad to isolate specific
      neurocognitive processes affected by both alcohol and aging. Compromises in
      cognitive efficiency (i.e., the ability to respond both quickly and accurately)
      have previously been identified in both elderly and acutely intoxicated
      individuals. METHODS: The present study employed a visual-spatial, 2-choice
      reaction time (RT) task to evaluate the interactive effects of aging and alcohol
      on cognitive efficiency. Our primary outcome measure was an efficiency ratio
      derived from each participant's response accuracy (ACC) and mean RT
      (%correct/RT). Younger (25 to 35; n = 22) and older (55 to 74; n = 37)
      participants were randomly assigned to receive either a placebo or moderate
      alcohol dose intended to produce a peak breath alcohol concentration of 0.04%.
      Participants performed the task at peak alcohol levels. RESULTS: A significant
      interaction between age group and dose assignment was observed, F(3, 55) = 4.86,
      p = 0.03, for the efficiency ratio. Younger participants who received alcohol
      performed significantly better than did their older counterparts regardless of
      alcohol condition and despite no differences in performance between the 2 age
      groups in the placebo condition. Additional correlation analyses between ACC and
      RT suggested that moderately intoxicated older adults become more accurate as
      response times increase. This relationship was not observed in older adults in
      the placebo condition. CONCLUSIONS: These data suggest that healthy individuals
      exhibit a differential susceptibility to the effects of alcohol depending on
      their age. Unfortunately, because of the presumed safety of moderate alcohol
      doses and a lack of studies investigating the interactive effects of acute
      alcohol consumption and aging, most individuals are unlikely to be aware of this
      relationship between alcohol consumption and age.

PMID- 22591191
TI  - Evaluation of left ventricular relaxation and filling pressures in obstructive
      hypertrophic cardiomyopathy: comparison between invasive hemodynamics and two
      dimensional speckle tracking.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is usually associated with marked
      diastolic dysfunction, characterized by impaired myocardial relaxation and
      increased myocardial stiffness. The noninvasive evaluation of diastolic function
      in these patients remains a challenge since usual methods have shown a modest
      correlation with invasive measurements of left ventricular (LV) relaxation and
      filling pressures. METHODS AND RESULTS: We retrospectively analyzed 44 patients
      with obstructive HCM who underwent cardiac catheterization and echocardiography
      performed within 48 hours. Standard echocardiographic diastolic parameters and
      systolic and diastolic myocardial mechanics (including longitudinal and
      circumferential strain [S] and strain rate [Sr]), LV rotation, and early reverse
      rotation rate (fraction of early apical reverse rotation [FEARR]) were correlated
      with diastolic hemodynamic indices. Estimated LA pressure by echo and the LV end
      diastolic pressure (LVEDP) or the LV pre-A pressure did not correlate.
      Longitudinal strain was low and circumferential strain was abnormally higher than
      normal. FEARR and negative dp/dt inversely correlated (R =-0.57, P = 0.0001), and
      early diastolic Sr to systolic Sr ratio (SrE/SrS) correlated with the LVEDP (r =
      0.61, P < 0.0001). Furthermore, a SrE to SrS ratio >= 0.79 had a sensitivity of
      87% and a specificity of 75% for predicting elevated LVEDP (>= 15 mmHg). Average
      circumferential strain rate during atrial contraction and LV pre-A pressure (r =
      0.62, P < 0.001) inversely correlated. CONCLUSIONS: FEARR is decreased in HCM and
      appears to be a good measure of diastolic dysfunction. Myocardial mechanics can
      be used to assess LV relaxation and filling pressures in patients with
      obstructive HCM.

PMID- 22591192
TI  - Rectal hypersensitivity as hallmark for irritable bowel syndrome: defining the
      optimal cutoff.
AB  - BACKGROUND: Visceral hypersensitivity is a frequently observed hallmark of
      irritable bowel syndrome (IBS). Studies have reported differently about the
      presence of visceral hypersensitivity in IBS resulting from lack of
      standardization of the barostat procedure and due to different criteria used to
      assess hypersensitivity. We aimed to calculate the optimal cutoff to detect
      visceral hypersensitivity in IBS. METHODS: A total of 126 IBS patients and 30
      healthy controls (HC) were included for assessment of visceroperception by
      barostat. Pain perception was assessed on a visual analogue scale (VAS). ROC
      curves were used to calculate optimal discriminative cutoff (pressure and VAS
      score) between IBS patients and HC to define hypersensitivity. Furthermore, pain
      perception to distension sequences below the pressure threshold for
      hypersensitivity was defined as allodynia. KEY RESULTS: Irritable bowel syndrome
      patients showed increased visceroperception compared to HC. Thresholds for first
      sensation and first pain were lower in IBS patients VS HC (P < 0.01). ROC-curves
      showed optimal discrimination between IBS patients and HC at 26 mmHg with a VAS
      cutoff >=20 mm. Using this criterion, hypersensitivity percentages were 63.5% and
      6.6% in IBS patients and HC, respectively. No significant differences were
      observed between IBS subtypes. Allodynia was found in a small number of patients
      (11%). CONCLUSIONS & INFERENCES: Optimal cutoff for visceral hypersensitivity was
      found at pressure 26 mmHg with a VAS >=20 mm, resulting in 63.5% of IBS patients
      being hypersensitive and 11% being allodynic. Standardization of barostat
      procedures and defining optimal cutoff values for hypersensitivity is warranted
      when employing rectal barostat measurements for research or clinical purposes.

PMID- 22591193
TI  - Multiplet discharges after electrical stimulation: new evidence for distal
      excitability changes in motor neuron disease.
AB  - We hypothesized that action potentials evoked by distal stimulation might trigger
      ectopic activity (multiplet discharges, MDs). By studying MDs, we investigated
      the involvement of the axonal part of the peripheral motor neuron in amyotrophic
      lateral sclerosis (ALS) and progressive muscular atrophy (PMA). We performed
      stimulated high-density surface EMG recordings of the thenar muscles in 10
      ALS/PMA patients, five recordings per patient over a three-month period.
      Furthermore, motor unit number estimates (MUNE) and ALSFRS-R scores were obtained
      in sessions 1 and 5. MDs were found in all patients, in 21% of the sampled motor
      units, and in response to 2.4% of the stimulations. The interspike interval range
      of the MD components was 2.9-6.5 ms, which is compatible only with a distal MD
      origin. The number of MDs, as percentage of the number of applied stimuli, was
      correlated with a decline in ALSFRS-R (r =0.80, p =0.006) and MUNE (r =0.72, p
      =0.02). In conclusion, MDs can be elicited with electrical stimulation in ALS and
      PMA patients. Analysis of MD characteristics provides further indications for
      pathophysiological excitability changes in the most distal part of the motor
      neuron. MDs are associated with clinical deterioration.

PMID- 22591194
TI  - Treatment with a coinducer of the heat shock response delays muscle denervation
      in the SOD1-G93A mouse model of amyotrophic lateral sclerosis.
AB  - We undertook a longitudinal study of the histological and biochemical changes at
      the neuromuscular junction (NMJ) in muscles of SOD1-G93A mice. We also assessed
      these functions in mice treated with a known heat shock protein inducer,
      arimoclomol. Tissue samples of treated and untreated mSOD mice were analysed for
      AChE and ChAT enzyme activities as markers of neuromuscular function. Sections of
      hindlimb muscles (TA, EDL and soleus) were also stained for succinate
      dehydrogenase and silver cholinesterase activities as well as for
      immunohistochemistry. Hsp70 levels were also measured from muscle samples using
      ELISA. Results showed that denervation and nerve sprouting were present at
      symptom onset in fast muscles, although slow muscles remained fully innervated.
      Cholinergic enzyme activities were reduced prior to denervation and declined
      further with disease progression. Reduction of endplate size, a slow to fast
      shift in muscle phenotype was also observed. Treatment with arimoclomol delayed
      the appearance of these changes, increased innervation, cholinergic enzyme
      activities and endplate size and reversed muscle fibre transformation. These
      beneficial effects of arimoclomol in muscles were accompanied by an increase in
      Hsp70 expression. In conclusion, our results indicate that pharmacological
      targeting of muscles at early stages of disease may be a successful strategy to
      ameliorate disease progression in ALS.

PMID- 22591196
TI  - Implementation of mixture design for formulation of albumin containing enteric
      coated spray-dried microparticles.
AB  - CONTEXT: Oral delivery of proteins has been a challenging as well as rapidly
      developing field. OBJECTIVE: To implement mixture design of experiment to develop
      enteric-coated microparticles containing bovine serum albumin. MATERIALS AND
      METHODS: Microparticles were prepared using Buchi Spray Dryer 191. Simplex
      lattice mixture design computed using JMP software was implemented to compare the
      gastric protection rendered by Eudragit FS30D, Eudragit L100-55, and Eudragit
      S100 in microparticulate form. Further, an extreme vertices mixture design was
      used to incorporate hydroxypropyl methylcellulose (HPMC) Chitosan in the
      formulation to delay the release. Microparticle recovery yield and protein
      content in microparticles were evaluated. RESULTS AND DISCUSSIONS: The design was
      statistically significant with Eudragit S100 resulting in protein release of < 5%
      in acidic buffer. The selected optimal formulation had 70% of Eudragit S, 25%
      HPMC, and 5% Chitosan. The release profiles of protein from Eudragit S alone and
      along with HPMC were compared. About 25% decrease in the amount of protein
      release was observed 6 h post exposure of microparticle to buffer of pH 6.8. The
      microparticle recovery yield reduced from 77.99% to 71.56% which is due to
      addition of HPMC into the formulation matrix. CONCLUSION: Although all three
      Eudragit polymers can be used for enteric coating, in the microparticulate form
      Eudragit S resulted in higher gastric protection. Also use of HPMC along with
      Eudragit S resulted in further sustained release.

PMID- 22591195
TI  - Safety, tolerability and pharmacodynamics of a skeletal muscle activator in
      amyotrophic lateral sclerosis.
AB  - This study was designed to evaluate the safety and tolerability of single doses
      of CK-2017357, an orally bioavailable fast skeletal muscle troponin activator, in
      patients with amyotrophic lateral sclerosis (ALS), and to explore pharmacodynamic
      markers related to strength, endurance, and function. Sixty-seven patients with
      ALS received single doses of placebo, CK-2017357 at 250 mg and 500 mg in random
      order, separated by one week. Safety measures assessments were performed, as well
      as tests of pulmonary function, limb muscle strength and endurance, and global
      impression of change. Pharmacokinetics of both CK-2017357 and riluzole were
      studied. Sixty-three patients completed all three dosing periods. CK-2017357 was
      well tolerated, with dizziness and general fatigue being the most frequent
      adverse events. Both patients and investigators perceived a dose-dependent
      benefit of CK-2017357 as measured by global impression of change. Maximum
      voluntary ventilation and submaximal handgrip endurance also improved. Only small
      changes were seen in maximal strength. In conclusion, single doses of 250 mg and
      500 mg of CK-2017357 were safe and well tolerated by patients with ALS. Measures
      of endurance appear to be improved in a dose-related fashion, and both patients
      and investigators perceived a global benefit. Further study of this agent is
      warranted.

PMID- 22591197
TI  - Synthesis and properties of new multinary silicides R5Mg5Fe4Al(x)Si(18-x) (R =
      Gd, Dy, Y, x ~ 12) grown in Mg/Al flux.
AB  - Reactions of iron, silicon, and R = Gd, Dy, or Y in 1:1 Mg/Al mixed flux produce
      well-formed crystals of R(5)Mg(5)Fe(4)Al(x)Si(18-x) (x ~ 12). These phases have a
      new structure type in tetragonal space group P4/mmm (a = 11.655(2) A, c =
      4.0668(8) A, Z = 1 and R(1) = 0.0155 for the Dy analogue). The structure features
      two rare earth sites and one iron site; the latter is in monocapped trigonal
      prismatic coordination surrounded by silicon and aluminum atoms. Siting of Al and
      Si was investigated using bond length analysis and (27)Al and (29)Si MAS NMR
      studies. The magnetic properties are determined by the R elements, with the Gd
      and Dy analogues exhibiting antiferromagnetic ordering at T(N) = 11.9 and 6.9 K
      respectively; both phases exhibit complex metamagnetic behavior with varying
      field.

PMID- 22591198
TI  - How water fosters a remarkable 5-fold increase in low-pressure CO2 uptake within
      mesoporous MIL-100(Fe).
AB  - The uptake and adsorption enthalpy of carbon dioxide at 0.2 bar have been studied
      in three different topical porous MOF samples, HKUST-1, UiO-66(Zr), and MIL
      100(Fe), after having been pre-equilibrated under different relative humidities
      (3, 10, 20, 40%) of water vapor. If in the case of microporous UiO-66, CO(2)
      uptake remained similar whatever the relative humidity, and correlations were
      difficult for microporous HKUST-1 due to its relative instability toward water
      vapor. In the case of MIL-100(Fe), a remarkable 5-fold increase in CO(2) uptake
      was observed with increasing RH, up to 105 mg g(-1) CO(2) at 40% RH, in parallel
      with a large decrease in enthalpy measured. Cycling measurements show slight
      differences for the initial three cycles and complete reversibility with further
      cycles. These results suggest an enhanced solubility of CO(2) in the water-filled
      mesopores of MIL-100(Fe).

PMID- 22591199
TI  - New beverages of lemon juice with elderberry and grape concentrates as a source
      of bioactive compounds.
AB  - Considering the health potential of lemon and berry fruits, different functional
      beverages rich in antioxidant phytochemicals, which demonstrated beneficial
      effects, were developed. To fulfill this objective, lemon juice was combined with
      2 different concentrates, elderberry and grape, in a proportion of 5% (w/v).
      Bioactive composition (flavonoids and vitamin C) and color stability, as well as
      the antioxidant capacity of mixtures, during a period of 56 d of storage, were
      studied. A protective role of anthocyanins on ascorbic acid preservation was
      noted for both lemon-berry blends, keeping vitamin C stable until the end of the
      storage. In addition, the new drink combining lemon and elderberry performed
      better than the grape-lemon mixture in terms of health-promoting phytochemicals
      content, just as in vitro antioxidant capacity and color characteristics.
      PRACTICAL APPLICATION: Beverages made from lemon juice and berries could
      contribute to develop new drinks with a prolonged preservation of bioactive
      compounds throughout storage, keeping an attractive color and a high antioxidant
      activity during long periods of time. The information obtained in the present
      work is in agreement to the rules of health and safety for juices established by
      the Directive of European Commission Dir2001/112/CE incorporated to the Spanish
      law through the RD1050/2003 regulation. Consequently, an improved performance of
      industrial products would be achieved.

PMID- 22591200
TI  - Electrostatic coupling and local structural distortions at interfaces in
      ferroelectric/paraelectric superlattices.
AB  - The performance of ferroelectric devices is intimately entwined with the
      structure and dynamics of ferroelectric domains. In ultrathin ferroelectrics,
      ordered nanodomains arise naturally in response to the presence of a depolarizing
      field and give rise to highly inhomogeneous polarization and structural profiles.
      Ferroelectric superlattices offer a unique way of engineering the desired
      nanodomain structure by modifying the strength of the electrostatic interactions
      between different ferroelectric layers. Through a combination of X-ray
      diffraction, transmission electron microscopy, and first-principles calculations,
      the electrostatic coupling between ferroelectric layers is studied, revealing the
      existence of interfacial layers of reduced tetragonality attributed to
      inhomogeneous strain and polarization profiles associated with the domain
      structure.

PMID- 22591201
TI  - Paediatric nutrition risk scores in clinical practice: children with inflammatory
      bowel disease.
AB  - BACKGROUND: There has been increasing interest in the use of nutrition risk
      assessment tools in paediatrics to identify those who need nutrition support.
      Four non-disease specific screening tools have been developed, although there is
      a paucity of data on their application in clinical practice and the degree of
      inter-tool agreement. METHODS: The concurrent validity of four nutrition
      screening tools [Screening Tool for the Assessment of Malnutrition in Paediatrics
      (STAMP), Screening Tool for Risk On Nutritional status and Growth (STRONGkids),
      Paediatric Yorkhill Malnutrition Score (PYMS) and Simple Paediatric Nutrition
      Risk Score (PNRS)] was examined in 46 children with inflammatory bowel disease.
      Degree of malnutrition was determined by anthropometry alone using World Health
      Organization International Classification of Diseases (ICD-10) criteria. RESULTS:
      There was good agreement between STAMP, STRONGkids and PNRS (kappa > 0.6) but
      there was only modest agreement between PYMS and the other scores (kappa = 0.3).
      No children scored low risk with STAMP, STRONGkids or PNRS; however, 23 children
      scored low risk with PYMS. There was no agreement between the risk tools and the
      degree of malnutrition based on anthropometric data (kappa < 0.1). Three children
      had anthropometry consistent with malnutrition and these were all scored high
      risk. Four children had body mass index SD scores < -2, one of which was scored
      at low nutrition risk. CONCLUSIONS: The relevance of nutrition screening tools
      for children with chronic disease is unclear. In addition, there is the potential
      to under recognise nutritional impairment (and therefore nutritional risk) in
      children with inflammatory bowel disease.

PMID- 22591202
TI  - Characterization of imipenem resistance mechanisms in Pseudomonas aeruginosa
      isolates from Turkey.
AB  - The emergence of carbapenem resistance in Pseudomonas aeruginosa threatens the
      efficacy of this important anti-pseudomonal antibiotic class. Between 2003 and
      2006, an increase in the number of carbapenem-resistant P. aeruginosa isolates at
      the Zonguldak Karaelmas University Hospital was observed (Zonguldak, Turkey). To
      assess the imipenem resistance mechanisms emerging in these P. aeruginosa
      isolates, they were characterized by amplified fragment length polymorphism
      typing, which revealed diversity among imipenem-resistant isolates as well as two
      clonally related outbreak groups. The molecular mechanism of carbapenem
      resistance was characterized in a representative isolate from each clonal group.
      Mutational disruption of oprD was the most frequently encountered resistance
      mechanism (23/27 isolates).

PMID- 22591203
TI  - Psychotherapist development: integration as a way to autonomy.
AB  - This study deals with the question of how therapists naturally develop an
      integrative perspective. A grounded theory analysis was conducted, based on
      retrospective interviews with seven experienced therapists (working together in
      the same training program). Adoption of an integrative perspective was found to
      be an unintended consequence of the development towards an autonomous personal
      therapeutic approach. This development is directed by two autonomous criteria
      (congruence and perceived efficacy) and results in intuitive integration.
      Complementary to this aspect is a heteronomous line of personal therapeutic
      approach development, characterized by two criteria (adherence and
      legitimization) and leading to identification. Autonomy and heteronomy are
      understood as general principles along which a therapist's development can be
      organized.

PMID- 22591204
TI  - Dysregulated expression of fatty acid oxidation enzymes and iron-regulatory genes
      in livers of Nrf2-null mice.
AB  - BACKGROUND AND AIM: Hepatic excessive iron may play a role in the pathogenesis of
      non-alcoholic steatohepatitis (NASH). Nrf2 is a master regulator of antioxidative
      responses. However, the role of Nrf2 in lipid and iron homeostasis remains
      unclear. Accordingly, it was examined how Nrf2 regulates lipid-related and iron
      regulatory genes after feeding a high-fat diet (HFD) with iron. METHODS: Wild
      type and Nrf2-null mice were fed the following diets: (i) control diet (4%
      soybean oil) for 12 weeks, (ii) control diet for 8 weeks followed by control diet
      containing 0.5% carbonyl iron for 4 weeks, (iii) HFD (4% soybean oil and 16%
      lard) for 12 weeks, (iv) HFD for 8 weeks followed by HFD containing 0.5% carbonyl
      iron for 4 weeks. Blood and livers were removed after 12 weeks. RESULTS: Nrf2
      null control mice exhibited a tendency towards higher hepatic triglycerides
      compared to wild-type control mice. Hepatic malondialdehyde was higher and
      hepatic iron levels tended to be higher in Nrf2-null mice than wild-type
      counterparts while on a HFD. The HFD with iron synergistically induced mRNA
      expression of Pparalpha targets, including Acox and Cpt1 in wild-type mice, yet
      the induction was diminished in Nrf2-null mice. Hepatic hepcidin and ferroportin
      1 mRNA expression were increased in wild-type mice after feeding a HFD with iron,
      but were unchanged in any group of Nrf2-null mice. CONCLUSIONS: Nrf2 deletion
      dysregulates hepatic mRNA expression of beta-oxidation enzymes and iron-related
      genes, possibly causing a trend for increased hepatic triglyceride and iron
      concentrations. Nrf2 may have roles in the progression of NASH.

PMID- 22591206
TI  - Mito-communications.

PMID- 22591205
TI  - Complete mitochondrial genome of black porgy Acanthopagrus schlegelii
      (Perciformes, Sparidae).
AB  - Black porgy, Acanthopagrus schlegelii, is a marine protandrous hermaphrodite and
      belongs to one of the most important species commercialized for food in various
      areas of Asia. In this study, the complete mitochondrial genome of A. schlegelii
      has been determined. The mitogenome was 16,649 bp in length and contained 13
      protein-coding genes, 2 rRNA genes, 22 tRNA genes and 2 non-coding regions. It
      shared 90.2%, 82.3%, and 82.1% mitogenome sequence with Acanthopagrus latus,
      Parargyrops edita, and Pagrus major, respectively.

PMID- 22591207
TI  - Complete mitochondrial genome of Acheilognathus signifer (Cypriniformes,
      Cyprinidae): comparison of light-strand replication origins from six
      Acheilognathus species.
AB  - Acheilognathus signifer (Cypriniformes, Cyprinidae) is an endemic, endangered
      fresh water fish species in the Korean peninsula. In this study, the
      mitochondrial genome of A. signifer was completely sequenced, which is 16,566 bp
      in length. The characteristics of the complete mitochondrial genome were
      described in detail.

PMID- 22591208
TI  - The association between dietary lignans, phytoestrogen-rich foods, and fiber
      intake and postmenopausal breast cancer risk: a German case-control study.
AB  - Phytoestrogens are structurally similar to estrogens and may affect breast cancer
      risk by mimicking estrogenic/antiestrogenic properties. In Western societies,
      whole grains and possibly soy foods are rich sources of phytoestrogens. A
      population-based case-control study in German postmenopausal women was used to
      evaluate the association of phytoestrogen-rich foods and dietary lignans with
      breast cancer risk. Dietary data were collected from 2,884 cases and 5,509
      controls using a validated food-frequency questionnaire, which included
      additional questions phytoestrogen-rich foods. Associations were assessed using
      conditional logistic regression. All analyses were adjusted for relevant risk and
      confounding factors. Polytomous logistic regression analysis was performed to
      evaluate the associations by estrogen receptor (ER) status. High and low
      consumption of soybeans as well as of sunflower and pumpkin seeds were associated
      with significantly reduced breast cancer risk compared to no consumption (OR =
      0.83, 95% CI = 0.70-0.97; and OR = 0.66, 95% CI = 0.77-0.97, respectively). The
      observed associations were not differential by ER status. No statistically
      significant associations were found for dietary intake of plant lignans, fiber,
      or the calculated enterolignans. Our results provide evidence for a reduced
      postmenopausal breast cancer risk associated with increased consumption of
      sunflower and pumpkin seeds and soybeans.

PMID- 22591210
TI  - Evaluation of non-ST segment elevation acute chest pain syndromes with a novel
      low-profile continuous imaging ultrasound transducer.
AB  - BACKGROUND: This investigation was designed to test the hypothesis that
      continuous cardiac imaging using an ultrasound transducer developed in our
      laboratory (ContiScan) is superior to electrocardiogram (ECG) monitoring in the
      diagnosis of coronary artery disease (CAD) in patients with acute non-ST segment
      elevation chest pain syndromes. METHODS: Seventy patients with intermediate to
      high probability of CAD who presented with typical anginal chest pain and no
      evidence of ST segment elevation on the ECG were studied. The 2.5-MHz transducer
      is spherical in its distal part mounted in an external housing to permit steering
      in 360 degrees. The transducer was placed at the left sternal border to image the
      left ventricular short-axis view and recorded on video tape at baseline, during
      and after episodes of chest pain. Two ECG leads were continuously monitored. The
      presence of CAD was confirmed by coronary arteriography or nuclear or
      echocardiographic stress testing. RESULTS: Twenty-four patients had regional wall
      motion abnormalities (RWMA) on their initial echo which were unchanged during the
      period of monitoring. All had evidence of CAD. Twenty-eight patients had
      transient RWMA. All had evidence of CAD. Eighteen patients had normal wall motion
      throughout the monitoring period, 14 of these had no evidence of CAD, and four
      had evidence of CAD. These four patients did not have chest pain during
      monitoring. The sensitivity, specificity, and accuracy of echocardiographic
      monitoring for diagnosing non-ST elevation myocardial infarction was 88%, 100%,
      and 91% respectively. The sensitivity, specificity, and accuracy of the ECG for
      diagnosis of CAD were 31%, 100%, and 52%, respectively. Echocardiography was
      superior to ECG (P < 0.001). CONCLUSIONS: The data indicate that continuous
      cardiac imaging is superior to ECG monitoring for the diagnosis of CAD in
      patients presenting with acute non-ST segment elevation chest pain syndromes.
      This technique could be a useful adjunct to ECG monitoring for myocardial
      ischemia in the acute care setting.

PMID- 22591209
TI  - Association of the ALDH1A1*2 promoter polymorphism with alcohol phenotypes in
      young adults with or without ALDH2*2.
AB  - BACKGROUND: Prior studies suggest a possible association of a promoter
      polymorphism in the ALDH1A1 gene ( ALDH1A1*2 ) with alcohol use or dependence.
      The aim of this study was to examine the association of ALDH1A1*2 with drinking
      behaviors in Asian young adults and to examine ALDH2 genotype as a potential
      moderator of these associations. METHODS: Asian young adults (n = 951) were
      recruited from 2 college sites for studies of genetic associations with alcohol
      use behavior. Participants completed comprehensive background questionnaires on
      demographics and drinking behavior. Fingertip blood samples were obtained for DNA
      extraction and analysis. RESULTS: Participants with the ALDH2*1/*2 genotype
      reported significantly lower levels (frequency and quantity) of drinking within
      the last 90 days, fewer numbers of heavy drinking episodes within the last 90
      days, and lower lifetime maximum consumption levels compared with ALDH2*1/*1
      participants. There were no significant main effects of ALDH1A1*2 on any drinking
      variables, nor was there a significant interaction between ALDH2 and ALDH1A1
      genotypes on drinking outcomes. CONCLUSIONS: The association of ALDH2*2 with
      reduced alcohol consumption replicates previous findings across numerous studies.
      Although ALDH1A1*2 was not associated with drinking levels, the lack of an
      ALDH1A1*2 effect in ALDH2*2 individuals is consistent with the only other study
      that has examined these associations in East Asian populations.

PMID- 22591211
TI  - "Blind periods" in screening for toxoplasmosis in pregnancy in Austria - a
      debate.
AB  - Recent studies from Austria, France and Italy have shown that there is a poor
      adherence to the screening scheme for maternal Toxoplasma infections in pregnancy
      demonstrated by the fact that many recommended examinations are missed. This
      leads to undetected infections and limits our knowledge of incidence of the
      disease. We discuss the negative consequences of this situation on research on
      treatment effectiveness and the outcomes of congenital toxoplasmosis. The
      responsible public health institutions should assume responsibility for
      appropriate surveillance of the screening programme and take measures to improve
      screening adherence during pregnancy. Screening should start as early as possible
      in pregnancy and the latest test should be done at delivery. Screening schedule
      should allow distinguishing infections from the first, second and third trimester
      of pregnancy, as the risk of materno-foetal transmission and outcomes in case of
      foetal infections varies by time.

PMID- 22591212
TI  - Interspecific genetics of speciation phenotypes: song and preference coevolution
      in Hawaiian crickets.
AB  - Understanding the genetic architecture of traits involved in premating isolation
      between recently diverged lineages can provide valuable insight regarding the
      mode and tempo of speciation. The repeated coevolution of male courtship song and
      female preference across the species radiation of Laupala crickets presents an
      unusual opportunity to compare the genetic basis of divergence across independent
      evolutionary histories. Previous studies of one pair of species revealed a
      polygenic basis (including a significant X chromosome contribution) to
      quantitative differences in male song and female acoustic preference. Here, we
      studied interspecific crosses between two phenotypically less-diverged species
      that represents a phylogenetically independent occurrence of intersexual
      signalling evolution. We found patterns consistent with an additive polygenic
      basis to differentiation in both song and preference (n(E) = 5.3 and 5.1 genetic
      factors, respectively), and estimate a moderate contribution of the X chromosome
      (7.6%) of similar magnitude to that observed for Laupala species with nearly
      twice the phenotypic divergence. Together, these findings suggest a similar
      genetic architecture underlying the repeated evolution of sexual characters in
      this genus and provide a counterexample to prevailing theory predicting an
      association between early lineage divergence and sex-linked 'major genes'.

PMID- 22591213
TI  - Selection of excipient, solvent and packaging to optimize the performance of
      spray-dried formulations: case example fenofibrate.
AB  - CONTEXT: Along with other options, solid dispersions prepared by spray drying
      offer the possibility of formulating poorly soluble drugs in a rapidly dissolving
      format. As a wide range of potential excipients and solvents is available for
      spray drying, it is usually necessary to carry out a comprehensive array of
      studies to arrive at an optimal formulation. OBJECTIVE: To study the influence of
      formulation parameters such as co-sprayed excipients, solvents and packaging on
      the manufacture, in vitro performance and stability of spray-dried oral drug
      products using fenofibrate as a model drug. MATERIALS AND METHODS: Solid
      dispersions of fenofibrate with different amorphous polymers were manufactured
      from two solvent systems by spray drying. These were characterized in terms of
      physicochemical properties, crystalline content and dissolution behavior in
      biorelevant media upon production and after storage in two packaging systems
      (Glass and Activ-Vials(TM)). RESULTS AND DISCUSSION: Spray drying the same
      formulation from two different solvents led to different physicochemical
      properties, dissolution behavior and long-term stability. The dissolution
      behavior and long-term stability also varied significantly among excipients. The
      viscosity of the polymer and the packaging material proved to be important to the
      long-term stability. CONCLUSION: For spray-dried products containing fenofibrate,
      the excipients were ranked according to dissolution and stability performance as
      follows: PVP derivatives >> HPMC 2910/15, HPMCAS-MF, HP-beta-CD >> PVP:PVA 2:8.
      EtOH 96% proved superior to acetone/water for spray drying with polymers. The
      results were used to propose a general approach to developing spray-dried
      formulations of poorly soluble drugs.

PMID- 22591214
TI  - Discovery and characterization of a large number of diagnostic markers to
      discriminate Oncorhynchus mykiss and O. clarkii.
AB  - Hybridization of cutthroat trout and steelhead/rainbow trout is ubiquitous where
      they are sympatric, either naturally or owing to introductions. The ability to
      detect hybridization and introgression between the two species would be greatly
      improved by the development of more diagnostic markers validated across the two
      species' many phylogenetic lineages. Here, we describe 81 novel genetic markers
      and associated assays for discriminating the genomes of these sister species.
      These diagnostic nucleotide polymorphisms were discovered by sequencing of
      rainbow trout expressed sequence tags (ESTs) in a diverse panel of both cutthroat
      trout and steelhead/rainbow trout. The resulting markers were validated in a
      large number of lineages of both species, including all extant subspecies of
      cutthroat trout and most of the lineages of rainbow trout that are found in
      natural sympatry with cutthroat trout or used in stocking practices. Most of
      these markers (79%) distinguish genomic regions for all lineages of the two
      species, but a small number do not reliably diagnose coastal, westslope and/or
      other subspecies of cutthroat trout. Surveys of natural populations and hatchery
      strains of trout and steelhead found rare occurrences of the alternative allele,
      which may be due to either previous introgression or shared polymorphism. The
      availability of a large number of genetic markers for distinguishing genomic
      regions originating in these sister species will allow the detection of both
      recent and more distant hybridization events, facilitate the study of the
      evolutionary dynamics of hybridization and provide a powerful set of tools for
      the conservation and management of both species.

PMID- 22591215
TI  - Student nurses' experience working with mentally challenged individuals in South
      Africa.
AB  - South African student nurses experience emotional discomfort that might influence
      their adjustment and coping while working with mentally challenged individuals.
      Adjustment and coping might impact on their mental health and support needed
      while working in this challenging context. Student nurses working with mentally
      challenged individuals experience emotional discomfort that may result in work
      related stress. The experiences of student nurses working with mentally
      challenged individuals were explored and described as it may influence their
      adjustment, coping and result in work-related stress, impacting on their mental
      health. The study used a qualitative, explorative, descriptive, contextual
      research design with a case study as strategy. Thirteen student nurses from a
      specific higher educational institution in Gauteng, South Africa, participated in
      the focus group interviews. The researcher utilized reflective journals, a
      reflective letter, naive sketches, drawings and field notes to collect data. Data
      analysis was done according to Tesch's descriptive method of open coding and
      theme analysis. A central storyline emerged where student nurses described
      working with mentally challenged individuals as a process of personal
      transformation that was initiated by an engagement on a deeper emotional level
      with these individuals. The process of personal transformation started a journey
      towards the discovery of meaning for the self, as student nurses. Student nurses
      working in challenging environments during their training may experience
      emotional discomfort and need additional support in coping and adjustment within
      this context. The nurse educator plays an important role in providing this
      support to manage work-related stress as well as in creating learning
      opportunities for the student nurses working in challenging contexts.

PMID- 22591216
TI  - alpha-Synuclein aggregation in the saliva of familial transthyretin amyloidosis:
      a potential biomarker.
AB  - Familial transthyretin amyloidosis (ATTR) is an autosomal dominant disease
      characterized by the formation of transthyretin (TTR) amyloid deposits. This
      crippling and fatal disease is associated with point mutations in TTR, a protein
      mainly produced in the liver. Hence, liver transplantation is the only treatment
      capable of halting disease progression. Ideally, liver transplantation should be
      performed as early as possible in the disease course before significant
      neurologic disability has been incurred. Early detection of disease before
      serious pathological lesions occur is crucial for the clinical management of
      patients and for morbidity delay. Unfortunately, the presence of TTR mutations by
      itself is not a predictor of disease onset or progression. In the present work,
      we observed an increased oligomerization of alpha-synuclein in the saliva of ATTR
      symptomatic individuals comparatively to asymptomatic carriers of the same TTR
      mutation and healthy control subjects. Based on this observation, we propose
      monitoring alpha-synuclein oligomers in saliva as a biomarker of ATTR
      progression. Since alpha-synuclein plays a major role in several
      neurodegenerative disorders, assessing its oligomerization state in this fluid
      provides a non-invasive approach to survey these pathologies.

PMID- 22591217
TI  - Enhancement of the third-order nonlinear optical properties in open-shell singlet
      transition-metal dinuclear systems: effects of the group, of the period, and of
      the charge of the metal atom.
AB  - Metal-metal multiply bonded complexes in their singlet state have been predicted
      to form a novel class of "sigma-dominant" third-order nonlinear optical compounds
      based on the results of dichromium(II) and dimolybdenum(II) systems (H. Fukui et
      al. J. Phys. Chem. Lett.2011, 2, 2063) whose second hyperpolarizabilities (gamma)
      are enhanced by the contribution of the dsigma electrons with an intermediate
      diradical character. In this study, using the spin-unrestricted coupled-cluster
      method with singles and doubles as well as with perturbative triples, we
      investigate the dependences of gamma on the group and on the period of the
      transition metals as well as on their atomic charges in several open-shell
      singlet dimetallic systems. A significant enhancement of gamma is observed in
      those dimetallic systems composed of (i) transition metals with a small group
      number, (ii) transition metals with a large periodic number, and (iii) transition
      metals with a small positive charge. From the decomposition of the gamma values
      into the contributions of dsigma, dpi, and ddelta electrons, the gamma
      enhancements are shown to originate from the dsigma contribution, because it
      corresponds to the intermediate diradical character region. Furthermore, the
      amplitude of dsigma contribution turns out to be related to the size of the
      d(z(2)) atomic orbital of the transition metal, which accounts for the dependence
      of gamma on the group, on the period, and on the charge of the metal atoms. These
      dependences provide a guideline for an effective molecular design of highly
      efficient third-order nonlinear optical (NLO) systems based on the metal-metal
      bonded systems.

PMID- 22591218
TI  - Photolytic generation of benzhydryl cations and radicals from quaternary
      phosphonium salts: how highly reactive carbocations survive their first
      nanoseconds.
AB  - UV irradiation (266 or 280 nm) of benzhydryl triarylphosphonium salts Ar(2)CH
      PAr(3)(+)X(-) yields benzhydryl cations Ar(2)CH(+) and/or benzhydryl radicals
      Ar(2)CH(*). The efficiency and mechanism of the photo-cleavage were studied by
      nanosecond laser flash photolysis and by ultrafast spectroscopy with a state-of
      the-art femtosecond transient spectrometer. The influences of the photo
      electrofuge (Ar(2)CH(+)), the photo-nucleofuge (PPh(3) or P(p-Cl-C(6)H(4))(3)),
      the counterion (X(-) = BF(4)(-), SbF(6)(-), Cl(-), or Br(-)), and the solvent
      (CH(2)Cl(2) or CH(3)CN) were investigated. Photogeneration of carbocations from
      Ar(2)CH-PAr(3)(+)BF(4)(-) or -SbF(6)(-) is considerably more efficient than from
      typical neutral precursors (e.g., benzhydryl chlorides or bromides). The
      photochemistry of phosphonium salts is controlled by the degree of ion pairing,
      which depends on the solvent and the concentration of the phosphonium salts. High
      yields of carbocations are obtained by photolyses of phosphonium salts with
      complex counterions (X(-) = BF(4)(-) or SbF(6)(-)), while photolyses of
      phosphonium halides Ar(2)CH-PPh(3)(+)X(-) (X(-) = Cl(-) or Br(-)) in CH(2)Cl(2)
      yield benzhydryl radicals Ar(2)CH(*) due to photo-electron transfer in the
      excited phosphonium halide ion pair. At low concentrations in CH(3)CN, the
      precursor salts are mostly unpaired, and the photo-cleavage mechanism is
      independent of the nature of the counter-anions. Dichloromethane is better suited
      for generating the more reactive benzhydryl cations than the more polar and more
      nucleophilic solvents CH(3)CN or CF(3)CH(2)OH. Efficient photo-generation of the
      most reactive benzhydryl cations (3,5-F(2)-C(6)H(3))(2)CH(+) and (4-(CF(3))
      C(6)H(4))(2)CH(+) was only achieved using the photo-leaving group P(p-Cl
      C(6)H(4))(3) and the counter-anion SbF(6)(-) in CH(2)Cl(2). The lifetimes of the
      photogenerated benzhydryl cations depend greatly on the decay mechanisms, which
      can be reactions with the solvent, with the photo-leaving group PAr(3), or with
      the counter-anion X(-) of the precursor salt. However, the nature of the photo
      leaving group and the counterion of the precursor phosphonium salt do not affect
      the rates of the reactions of the obtained benzhydryl cations toward added
      nucleophiles. The method presented in this work allows us to generate a wide
      range of donor- and acceptor-substituted benzhydryl cations Ar(2)CH(+) for the
      purpose of studying their electrophilic reactivities.

PMID- 22591219
TI  - New CBP mutations in Brazilian patients with Rubinstein-Taybi syndrome.

PMID- 22591220
TI  - High-dose, ten-day esomeprazole, amoxicillin and metronidazole triple therapy
      achieves high Helicobacter pylori eradication rates.
AB  - BACKGROUND: Strong acid inhibition using esomeprazole increases cure rates with
      triple therapy and 10-day treatments are more effective than 7-day ones. The
      combination of amoxicillin plus metronidazole at full doses, and using a
      physiologically-correct schedule three times a day, and has been shown to
      overcome metronidazole resistance and to achieve good eradication rates. AIMS: To
      assess the eradication rate of a new first-line treatment regimen associating
      strong acid inhibition, amoxicillin and metronidazole and to evaluate tolerance.
      METHODS: Patients from eight hospitals were included. Helicobacter pylori status
      was assessed by at least one of the following: histology, culture, rapid urease
      test or urea breath test (UBT). Ten-day treatment was prescribed comprising
      esomeprazole 40 mg twice a day plus amoxicillin 1 g and metronidazol 500 mg both
      three times a day. Helicobacter pylori cure was assessed by UBT. RESULTS: A
      hundred and thirty-six patients were enrolled. Mean age was 52.6 +/- 16 years and
      59.6% of patients were men. Main indications for treatment were: uninvestigated
      dyspepsia (13.6%); functional dyspepsia (18.2%); gastric ulcer (21.8%); and
      duodenal ulcer (39.8%). Helicobacter pylori eradication was achieved in 112 of
      the 127 patients who returned for follow-up. Eradication rates were 82.4% (95%
      CI: 74.7-88.1) by intention-to-treat analysis and 88.2% (95% CI: 81.2-92.8) by
      per protocol. Treatment was well tolerated and no major side effects were
      reported. Nine patients complained of mild side effects. CONCLUSIONS: Cure rates
      of the combination of esomeprazole, amoxicillin and metronidazole are high and
      the treatment was well tolerated. This pilot study warrants the comparison of
      this schedule with current standards.

PMID- 22591221
TI  - Modification of ginseng flavors by bitter compounds found in chocolate and
      coffee.
AB  - Ginseng is not widely accepted by U.S. consumers due to its unfamiliar flavors,
      despite its numerous health benefits. Previous studies have suggested that the
      bitter compounds in chocolate and coffee may mask the off-flavors of ginseng. The
      objectives of this study were to: (1) profile sensory characteristics of ginseng
      extract solution, caffeine solution, cyclo (L-Pro-L-Val) solution, theobromine
      solution, and 2 model solutions simulating chocolate bitterness; and (2)
      determine the changes in the sensory characteristics of ginseng extract solution
      by the addition of the bitter compounds found in chocolate and coffee. Thirteen
      solutions were prepared in concentrations similar to the levels of the bitter
      compounds found in coffee and chocolate products. Twelve panelists participated
      in a descriptive analysis panel which included time-intensity ratings. Ginseng
      extract was characterized as sweeter, starchier, and more green tea than the
      other sample solutions. Those characteristics of ginseng extract were effectively
      modified by the addition of caffeine, cyclo (L-Pro-L-Val), and 2 model solutions.
      A model solution simulating dark chocolate bitterness was the least influenced in
      intensities of bitterness by the addition of ginseng extract. Results from time
      intensity ratings show that the addition of ginseng extract increased duration
      time in certain bitterness of the 2 model solutions. Bitter compounds found in
      dark chocolate could be proposed to effectively mask the unique flavors of
      ginseng. Future studies blending aroma compounds of chocolate and coffee into
      such model solutions may be conducted to investigate the influence on the
      perception of the unique flavors through the congruent flavors.

PMID- 22591222
TI  - Podocyte culture: tricks of the trade.
AB  - Podocytes (glomerular epithelial cells) lie on the urinary aspect of the
      glomerular capillary and play a key role in the selective filter that underlies
      kidney function. They are injured in various forms of renal disease: the extents
      of this injury and its reversibility have major implications for treatment and
      prognosis. Until recently, podocytes were difficult to study in vitro because of
      a previous lack of techniques for obtaining differentiated cells in quantities
      adequate for research. In recent years, this problem has been solved for rodent
      and human podocytes and there has been an explosion of research using cultured
      cells. These authors have led the development and characterization of human
      podocyte cell lines and in this article describe the methods that have allowed
      them to do this.

PMID- 22591223
TI  - Solid-state syntheses of coordination polymers by thermal conversion of molecular
      building blocks and polymeric precursors.
AB  - The syntheses and crystal structures of a mononuclear cadmium complex and five
      novel coordination polymers based on 1,2,4-triazolyl benzoates are presented. The
      compounds (infinity)(3)[Cd(H-Me-trz-pba)(2)] (2), (infinity)(3)[Cd(Me-3py-trz
      pba)(2)] (4), and (infinity)(3)[Zn(H-Me-trz-pba)(2)] (6) can be obtained by
      solvothermal synthesis or simple heating of the starting materials in appropriate
      solvents, and are also accessible by thermal conversion of the complex [Cd(H-Me
      trz-pba)(2)(H(2)O)(4)] (1), the one-dimensional (1D) coordination polymer
      (infinity)(1)[Cd(Me-3py-trz-pba)(2)(H(2)O)(2)].H(2)O (3), and the porous three
      dimensional (3D) framework (infinity)(3)[Zn(H-Me-trz-pba)2].4H(2)O (5),
      respectively. The driving force for these conversions is the formation of
      thermally stable, nonporous, crystalline 3D coordination polymers. The structural
      transformations are accompanied by the loss of water and reveal significant
      changes of the coordination spheres of the metal ions caused by a rearrangement
      of the triazolyl benzoate ligands. Compounds 2, 4, 5, and 6 exhibit 4- and 5-fold
      interpenetration of diamondoid networks (dia) and are thermally stable up to 380 
      degrees C.

PMID- 22591224
TI  - Technology-driven dietary assessment: a software developer's perspective.
AB  - Dietary researchers need new software to improve nutrition data collection and
      analysis, although the creation of information technology is difficult. Software
      development projects may be unsuccessful as a result of an inadequate
      understanding of needs, management problems, technology barriers or legal
      hurdles. Cost over-runs and schedule delays are common. Barriers facing
      scientific researchers developing software include workflow, cost, schedule and
      team issues. Different methods of software development and the role that
      intellectual property rights play are discussed. A dietary researcher must
      carefully consider multiple issues to maximise the likelihood of success when
      creating new software. 

PMID- 22591225
TI  - Anterior corneal optical irregularity measured by higher-order aberrations
      induced by a broad beam excimer laser.
AB  - BACKGROUND: The aim was to analyse anterior corneal optical irregularity in
      patients receiving photorefractive keratectomy (PRK) and laser in situ
      keratomileusis (LASIK) with a conventional broad beam laser. METHODS: Pre- and
      post-operative anterior corneal aberrations including Zernike coefficients and
      root mean squares of higher-order aberrations were measured and derived with a
      Placido-ring-based corneal topographer and wavefront software, respectively, from
      768 right eyes of patients receiving either PRK or LASIK for myopia with a
      conventional broad beam excimer laser in National Taiwan University Hospital,
      Taipei, Taiwan. Multiple linear regression models selected by Mallows' Cp
      criteria were used to evaluate predictability of surgically induced aberrations
      and relevant factors. RESULTS: Mean attempted spherical equivalent correction was
      -7.37 +/- 2.33 D (range: -16.5 to -1.95). Root mean squares of higher-order
      aberrations and variances of Zernike coefficients all increased significantly
      after surgery (p < 0.01). All post-operative higher-order aberrations increased
      with the amount of attempted myopic correction and secondary astigmatism
      increased with attempted cylindrical correction. LASIK surgery induced less coma
      and third-order aberrations but more fifth- and sixth-order aberrations than PRK,
      although squared partial correlation coefficients were low. Larger optic and
      transitional zones meant fewer higher-order aberrations after surgery. Younger
      patients tended to have more surgically induced aberrations in the 3.0 mm pupil
      zone. CONCLUSIONS: Anterior corneal optical irregularity increased tremendously
      after refractive surgery by conventional broad beam lasers and correlated with
      greater attempted myopic correction, younger age and a smaller treatment zone.
      The effect of corneal flaps on post-operative corneal irregularity differed
      trivially.

PMID- 22591226
TI  - The stress-activated protein kinase FgOS-2 is a key regulator in the life cycle
      of the cereal pathogen Fusarium graminearum.
AB  - Fusarium graminearum is one of the most destructive pathogens of cereals and a
      threat to food and feed production worldwide. It is an ascomycetous plant
      pathogen and the causal agent of Fusarium head blight disease in small grain
      cereals and of cob rot disease in maize. Infection with F. graminearum leads to
      yield losses and mycotoxin contamination. Zearalenone (ZEA) and deoxynivalenol
      (DON) are hazardous mycotoxins; the latter is necessary for virulence toward
      wheat. Deletion mutants of the F. graminearum orthologue of the Saccharomyces
      cerevisiae Hog1 stress-activated protein kinase, FgOS-2 (DeltaFgOS-2), showed
      drastically reduced in planta DON and ZEA production. However, DeltaFgOS-2
      produced even more DON than the wild type under in vitro conditions, whereas ZEA
      production was similar to that of the wild type. These deletion strains are
      dramatically reduced in pathogenicity toward maize and wheat. We constitutively
      expressed the fluorescent protein dsRed in the deletion strains and the wild
      type. Microscopic analysis revealed that DeltaFgOS-2 is unable to reach the
      rachis node at the base of wheat spikelets. During vegetative growth, DeltaFgOS-2
      strains exhibit increased resistance against the phenylpyrrole fludioxonil.
      Growth of mutant colonies on agar plates supplemented with NaCl is reduced but
      conidia formation remained unchanged. However, germination of mutant conidia on
      osmotic media is severely impaired. Germ tubes are swollen and contain multiple
      nuclei. The deletion mutants completely fail to produce perithecia and
      ascospores. Furthermore, FgOS-2 also plays a role in reactive oxygen species
      (ROS)-related signaling. The transcription and activity of fungal catalases is
      modulated by FgOS-2. Among the genes regulated by FgOS-2, we found a putative
      calcium-dependent NADPH-oxidase (noxC) and the transcriptional regulator of ROS
      metabolism, atf1. The present study describes new aspects of stress-activated
      protein kinase signaling in F. graminearum.

PMID- 22591227
TI  - Do female parasitoid wasps recognize and adjust sex ratios to build cooperative
      relationships?
AB  - Sex allocation theories provide excellent opportunities to investigate not only
      the extent to which individuals' behaviour is adaptive, but also how they use
      relevant information for their decision-making. Here, we investigated whether
      female parasitoid wasps recognize the sex ratios of other females and adjust
      their laying sex ratios accordingly. Specifically, we tested the prediction of
      reciprocal cooperation over sex allocation. Theory predicts more female-biased
      (cooperative) sex ratios than in the interest of individual benefit, when a
      restricted number of ovipositing females interact for a long period and their
      offspring mate within the natal patch. This is because the female-biased sex
      ratio reduces competition for mates among the male offspring of the females and
      increases the overall reproductive productivity of the patch. In this case,
      females would be expected to respond to more even (noncooperative) sex ratios by
      others and to retaliate by also producing a less female-biased sex ratio to avoid
      exploitation by defectors. However, contrary to this prediction, our experiment
      using a sterile male technique showed that female Melittobia australica did not
      change their offspring sex ratios in response to the sex ratios produced by other
      females. This suggests that their extremely female-biased sex ratios cannot be
      explained by reciprocity. A meta-analysis of studies examining sex recognition
      ability in parasitoid wasps also did not support the predicted pattern of
      relevant sex ratio adjustment, suggesting that parasitoid females do not possess
      this ability. Here, we discuss the conditions necessary for the evolution of
      reciprocity linked to recognition ability.

PMID- 22591228
TI  - Effects of cross-fostering on alcohol preference and correlated responses to
      selection in high- and low-alcohol-preferring mice.
AB  - BACKGROUND: Selectively bred rodent lines are valuable tools for investigating
      gene * environment interactions related to risk for alcoholism in humans. Early
      maternal environment is one particular factor known for critically influencing
      neural, hormonal, and behavioral outcomes in adulthood. Cross-fostering is a
      procedure that may be used to explore the role of genotype-dependent maternal
      influences on phenotypic variability in adulthood. The purpose of these
      experiments was to examine the effects of cross-fostering on free-choice alcohol
      drinking and correlated responses to selection for alcohol preference in mice
      selectively bred for high (HAP2) and low (LAP2) alcohol preference. METHODS: Mice
      were assigned to one of the following treatments: SHAM (pups that were fostered
      to their original biological mother), IN (pups that were fostered to a different
      mother of the same line), and CROSS (pups that were fostered to a mother of a
      different line). Mice were tested in adulthood for (i) free 24-hour access to
      alcohol for a period of 28 days; (ii) the expression of the acoustic startle
      response and fear-potentiated startle (FPS); and (iii) handling-induced
      convulsions (HICs) during acute alcohol withdrawal. RESULTS: Overall, the
      expression of the alcohol preference selection phenotype was robust in all groups
      (HAP2 > LAP2). Cross-fostering produced a moderate but significant reduction in
      g/kg alcohol drinking and preference scores in HAP2 mice (CROSS < SHAM) but had
      no effect in LAP2 mice. Cross-fostering did not affect the expression of
      correlated responses to selection: acoustic startle response (HAP2 > LAP2), FPS
      (HAP2 > LAP2), HICs (LAP2 > HAP2). CONCLUSIONS: It appears that maternal
      environment can modify the expression of the high-alcohol-preference phenotype in
      HAP2 selectively bred mice. These results suggest a gene * environment
      interaction with respect to the expression of the high-alcohol-preference
      selection phenotype but not correlated responses to selection.

PMID- 22591229
TI  - The book, the stories, the people: an ongoing dialogic narrative inquiry study
      combining a practice development project. Part 2: the practice development
      context.
AB  - This paper is the second part of a two-article practice development report. It
      builds on the first part by introducing and discussing a Writing for Recovery
      practice development project, conducted at two UK sites. The paper begins by
      briefly describing the project within the context of helping mental health users,
      carers and survivors develop skills in creative writing in order to engage in the
      process of narrative re-storying in line with preferred identity. A selective
      overview of broad and focal background literature relevant to the project is then
      provided in order to position it within a values-based mental health nursing
      practice. Following this, the specific plan for running the project is briefly
      summarized, covering actual and anticipated ethical issues. The paper ends with a
      discussion of dissemination aims.

PMID- 22591230
TI  - Disparities in late stage diagnosis, treatment, and breast cancer-related death
      by race, age, and rural residence among women in Georgia.
AB  - The objectives of this study were to examine the outcomes of late stage breast
      cancer diagnosis, receiving first course treatment, and breast cancer-related
      death by race, age, and rural/urban residence in Georgia. The authors used cross
      sectional and follow-up data (1992-2007) for Atlanta and Rural Georgia cancer
      registries that are part of the National Cancer Institute's Surveillance,
      Epidemiology, and End Results Program (N = 23,500 incident breast cancer cases in
      non-Hispanic whites or non-Hispanic African Americans). Multilevel modeling and
      Cox proportional hazard models revealed that compared to whites, African American
      women had significantly increased odds of late stage diagnosis (odds ratio [OR] =
      2.08, p = 0.0001) and unknown tumor stage (OR = 1.27, p = 0.0001), decreased odds
      of receiving radiation (OR = 0.93, p = 0.041) or surgery (OR = 0.50, p = 0.0001),
      and increased risk of death following breast cancer diagnosis (hazard rate ratio
      [HR] = 1.50, p = 0.0001). Increased age was significantly associated with the
      odds of late/unknown stage at diagnosis, worse treatment, and survival. Women
      residing in rural areas had significantly decreased odds of receiving radiation
      and surgery with radiation (OR = 0.59, p = 0.0001), and for receiving breast
      conserving surgery compared to mastectomy (OR = 0.73, p = 0.005). Factors
      affecting each level of the breast cancer continuum are distinct and should be
      examined separately. Efforts are needed to alleviate disparities in breast cancer
      outcomes in hard-to-reach populations.

PMID- 22591231
TI  - Multiple social roles, health, and sickness absence--a five-year follow-up study
      of professional women in Sweden.
AB  - The aim of this study was to analyze associations between changes in social roles
      and physical health, mental well-being, psychiatric disorder, and long-term
      sickness absence over a five-year period. The study was part of a general
      population-based multipurpose project. Professional women from six birth cohorts
      born in 1935, 1945, 1955, 1965, 1970, or 1975 (N = 532) were interviewed twice.
      Self-rated information on physical health, mental well-being, long-term sickness
      absence, and changes in social roles was used. Information on psychiatric
      disorders was based on Diagnostic and Statistical Manual of Mental Disorders-III
      R and Diagnostic and Statistical Manual of Mental Disorders-IV diagnoses.
      Multivariate logistic regressions were adjusted for age, socio-economic position,
      alcohol dependence and abuse, and health at baseline. An increase in number of
      social roles was associated with lower odds for poor mental well-being, odds
      ratio (OR) 0.4 (confidence interval [CI] 0.2 to 0.8), while a decrease was
      associated with higher odds for poor mental well-being, OR 4.5 (CI 1.8 to 11.0),
      psychiatric disorder, OR 2.6 (1.0 to 6.8), and sickness absence, OR 4.4 (1.6 to
      11.7). The results indicated that an increase in number of social roles might be
      protective against poor mental well-being, while a decrease in number of roles
      might be related to increased psychiatric disorders and long-term sickness
      absence. More studies on long-term health implications of gender-specific
      experiences are needed.

PMID- 22591232
TI  - Socio-economic determinants and self-reported depressive symptoms during
      postpartum period.
AB  - The researchers' aims were to estimate the prevalence of postpartum depressive
      symptoms in Italy. Cross-sectional data from the survey, "Health and use of
      health care in Italy" were analyzed. The authors focused on 5,812 women, pregnant
      some time during five years before the survey. Multiple logistic regression was
      used to evaluate risk factors independently associated with postpartum depressive
      symptoms. Evaluation of seasonal trends was also performed.In the total sample,
      23.5% (n = 1,365) reported having suffered postpartum depressive symptoms: 20.7%
      experienced baby blues, and 2.8% postpartum depression. Factors significantly
      associated with baby blues were, among others, living in northern or central
      areas (adjusted odds ratio [aOR] 1.88; 95%CI 1.57-2.15 and 1.40; 95%CI 1.20-1.63,
      respectively), history of depression (aOR 1.34; 95%CI 1.15-1.56), and attendance
      at antenatal classes (aOR 1.13; 95%CI 1.04-1.22). Factors significantly
      associated with postpartum depression were: anamnesis of depression (aOR 3.32;
      95%CI 2.69-4.09), gaining more than 16 kg of weight during pregnancy (aOR 1.48;
      95%CI 1.03-2.12), and undergoing a cesarean section (planned: aOR 1.56; 95%CI
      1.05-2.29; unplanned: aOR 1.78; 95%CI 1.16-2.73). Multiparity was a protective
      factor both for baby blues (aOR 0.80; 95%CI 0.70-0.91), and postpartum depression
      (aOR 0.71; 95%CI 0.51-0.98). No clear seasonality was observed for postpartum
      depression, while for baby blues a certain aggregation of events was registered
      during the central months of the year. The authors' study highlighted variables
      associated with baby blues and postpartum depression to target screening for
      women for postpartum depressive symptoms.

PMID- 22591233
TI  - Validation of the Greek maternal adjustment and maternal attitudes scale for
      assessing early postpartum adjustment.
AB  - The Maternal Adjustment and Maternal Attitudes Scale is a self- administered
      scale, designed for use in primary care settings to identify postpartum maternal
      adjustment problems regarding body image, sex, somatic symptoms, and marital
      relationships. Women were recruited within four weeks of giving birth. Responses
      to the Maternal Adjustment and Maternal Attitudes Scale were compared for
      agreement with responses to the Edinburgh Postnatal Depression Scale as a gold
      standard. Psychometric measurements included: reliability coefficients,
      explanatory factor analysis, and confirmatory analysis by linear structural
      relations. A receiver operating characteristic analysis was carried out to
      evaluate the global functioning of the scale. Of 300 mothers screened, 121
      (40.7%) were experiencing difficulties in maternal adjustment and maternal
      attitudes. Scores on the Maternal Adjustment and Maternal Attitudes Scale
      correlated well with those on the Edinburgh Postnatal Depression Scale. The
      internal consistency of the Maternal Adjustment and Maternal Attitudes Scale,
      Greek version-tested using Cronbach's alpha coefficient-was 0.859, and that of
      Guttman split-half coefficient was 0.820. Findings confirmed the
      multidimensionality of the Maternal Adjustment and Maternal Attitudes Scale,
      demonstrating a six-factor structure. The area under the receiver operating
      characteristic curve was 0.610, and the logistic estimate for the threshold score
      of 57/58 fitted the model sensitivity at 68% and model specificity at 64.6%. Data
      confirmed that the Greek version of the Maternal Adjustment and Maternal
      Attitudes Scale is a reliable and valid screening tool for both clinical practice
      and research purposes to detect postpartum adjustment difficulties.

PMID- 22591234
TI  - Risk of developing breast cancer by utilizing Gail model.
AB  - The Gail model has been widely used to quantify an individual woman's risk of
      developing breast cancer by using important clinical parameters, usually for
      clinical counselling purposes or to determine eligibility for mammography and
      genetic tests. The aim of the present study was to estimate the five-year and
      lifetime breast cancer risk among women in Rasht, Iran. In this cross-sectional
      study, 314 women were evaluated at Alzahra Women Hospital in 2007. Participants
      were >=35 years of age without a history of breast cancer. Risk estimation was
      performed using the computerized Gail model. A five-year risk >1.66% was
      considered high-risk; 5.1% of women were high-risk. The mean five-year breast
      cancer risk was 0.8% (SD+/-1). Mean breast cancer risk up to the age of 90 years
      (lifetime risk) was 9.0% (SD+/-3.9%); 16.2% of the participants had a five-year
      risk higher than the average woman of the same age, and 18.2% had the same risk.
      Also for the lifetime risk, 11.1% of the women had higher risk and 1.6% had the
      same risk as the average woman. Routine use of the Gail model is recommended for
      identifying women at high average risk for increasing the survival of women from
      breast cancer.

PMID- 22591235
TI  - Facets of career satisfaction for women physicians in the United States: a
      systematic review.
AB  - Women make up a growing proportion of the physician workforce, and their career
      satisfaction may affect their health. The authors hypothesized that many facets
      adversely affecting career satisfaction in women physicians were extrinsic,
      therefore, preventable or modifiable. The authors conducted a systematic review
      of the literature in English published through February 2010 to examine facets of
      career satisfaction of U.S. women physicians. The authors used the women
      physician AND job satisfaction OR career satisfaction Medical Subject Headings
      (MeSH) terms, and reviewed bibliographies of key articles to ensure inclusion of
      relevant studies. The authors used the "Strengthening the Reporting of
      Observation Studies in Epidemiology" quality tool. Of an initial 1,000 studies,
      only 30 met the inclusion criteria. Facets reported most frequently to influence
      career satisfaction for women physicians were income/prestige, practice
      characteristics, and personal/family characteristics. Overall, career
      satisfaction for women and men physicians was 73.4% (range = 56.4% to 90%) and
      73.2% (range = 59% to 90%), respectively. When compared with men, women
      physicians were more concerned with perceived lack of time for relationships with
      patients, colleagues, and family; less satisfied with mentoring relationships and
      support from all sources; and less satisfied with career-advancement
      opportunities, recognition, and salary. Career satisfaction can affect health, as
      well as health and safety of patients. Many factors adversely affecting career
      satisfaction for women physicians are extrinsic and, therefore, modifiable.

PMID- 22591237
TI  - Myocardial mechanics: understanding and applying three-dimensional speckle
      tracking echocardiography in clinical practice.
AB  - Speckle tracking echocardiography (STE) is an emerging tool to characterize and
      quantify myocardial segmental and rotational mechanics. This literature review is
      aimed at clinical and academic cardiologists to provide: (1) a conceptual
      framework of STE to initiate understanding of myocardial mechanics; (2) evidence
      that three-dimensional (3D) STE overcomes the problems of time-consuming data
      acquisition and postprocessing seen with two-dimensional STE; and (3)
      illustrative clinical cases with analysis of myocardial mechanics via 3D STE to
      show the incremental value of strain in clinical decision making.

PMID- 22591236
TI  - Prevalence and clinical features of respiratory syncytial virus in children
      hospitalized for community-acquired pneumonia in northern Brazil.
AB  - BACKGROUND: Childhood pneumonia and bronchiolitis is a leading cause of illness
      and death in young children worldwide with Respiratory Syncytial Virus (RSV) as
      the main viral cause. RSV has been associated with annual respiratory disease
      outbreaks and bacterial co-infection has also been reported. This study is the
      first RSV epidemiological study in young children hospitalized with community
      acquired pneumonia (CAP) in Belem city, Para (Northern Brazil). METHODS: With the
      objective of determining the prevalence of RSV infection and evaluating the
      patients' clinical and epidemiological features, we conducted a prospective study
      across eight hospitals from November 2006 to October 2007. In this study, 1,050
      nasopharyngeal aspirate samples were obtained from hospitalized children up to
      the age of three years with CAP, and tested for RSV antigen by direct
      immunofluorescence assay and by Reverse Transcription Polymerase Chain Reaction
      (RT-PCR) for RSV Group identification. RESULTS: RSV infection was detected in 243
      (23.1%) children. The mean age of the RSV-positive group was lower than the RSV
      negative group (12.1 months vs 15.5 months, p<0.001) whereas gender distribution
      was similar. The RSV-positive group showed lower means of C-reactive protein
      (CRP) in comparison to the RSV-negative group (15.3 vs 24.0 mg/dL, p<0.05).
      Radiological findings showed that 54.2% of RSV-positive group and 50.3% of RSV
      negative group had interstitial infiltrate. Bacterial infection was identified
      predominantly in the RSV-positive group (10% vs 4.5%, p<0.05). Rhinorrhea and
      nasal obstruction were predominantly observed in the RSV-positive group. A co
      circulation of RSV Groups A and B was identified, with a predominance of Group B
      (209/227). Multivariate analysis revealed that age under 1 year (p<0.015), CRP
      levels under 48 mg/dL (p<0.001) and bacterial co-infection (p<0.032) were
      independently associated with the presence of RSV and, in the analyze of
      symptoms, nasal obstruction were independently associated with RSV-positive group
      (p<0.001). CONCLUSION: The present study highlights the relevance of RSV
      infection in hospitalized cases of CAP in our region; our findings warrant the
      conduct of further investigations which can help design strategies for
      controlling the disease.

PMID- 22591238
TI  - New pathological insights into cardiac amyloidosis: implications for non-invasive
      diagnosis.
AB  - BACKGROUND: Knowledge of the patterns of myocardial amyloid accumulation could
      improve the interpretation of electrocardiographic, echocardiographic and
      magnetic resonance imaging findings of amyloidosis. We assessed the extent and
      pattern of myocardial amyloid infiltration in explanted or autopsied hearts of
      patients with cardiomyopathy related to acquired monoclonal immunoglobulin light
      chain (AL) or hereditary transthyretin (TTR) related amyloidosis (ATTR). METHODS:
      We analyzed nine explanted/autopsied hearts from patients with AL (n = 4) and
      ATTR (n = 5) cardiac amyloidosis. For each heart, a biventricular histological
      macrosection was obtained at mid-ventricular level and analyzed with both
      inspective and computer-assisted histologic and histomorphometric analysis aimed
      in particular at quantifying muscle cells, fibrosis and amyloid infiltration.
      RESULTS: The extent of amyloid infiltration of the left ventricle (LV) ranged
      from 45 to 76% (median [interquartile range (IQR)] = 57% [51-64]) of the overall
      surface. Although LV trabecular and subendocardial were the most infiltrated
      layers (45-94%, median [IQR] = 73% [67-84] and from 44 to 71%, median [IQR] = 57%
      [49-59], respectively), intra- and inter-patient heterogeneity was high. Three
      main patterns of amyloid infiltration of the LV were identified: diffuse (five
      cases), mainly subendocardial (two cases), and mainly segmental (two cases). The
      extent of amyloid infiltration of the right ventricle ranged from 48 to 93%
      (median [IQR] = 61% [59-83]); contributions of parietal and trabecular layers
      ranged from 32 to 99% (median [IQR] = 63% [47-88]) and from 49 to 93% (median
      [IQR] = 74% [64-79]), respectively. CONCLUSIONS: In amyloidotic cardiomyopathy,
      amyloid deposition is highly heterogeneous. Different patterns of infiltration
      are identifiable, including diffuse, mainly segmental and mainly subendocardial.
      Awareness of this variability can help the interpretation of ECGs,
      echocardiograms and magnetic resonance imaging.

PMID- 22591239
TI  - Nondestructive sampling of insect DNA from defensive secretion.
AB  - Nondestructive techniques to obtain DNA from organisms can further genetic
      analyses such as estimating genetic diversity, dispersal and lifetime fitness,
      without permanently removing individuals from the population or removing body
      parts. Possible DNA sources for insects include frass, exuviae, and wing and leg
      clippings. However, these are not feasible approaches for organisms that cannot
      be removed from their natural environment for long periods or when adverse
      effects of tissue removal must be avoided. This study evaluated the impacts and
      efficacy of extracting haemolymph from a defensive secretion to obtain DNA for
      amplification of microsatellites using a nondestructive technique. A secretion
      containing haemolymph was obtained from Bolitotherus cornutus (the forked fungus
      beetle) by perturbation of the defensive gland with a capillary tube. A
      laboratory experiment demonstrated that the sampling methodology had no impact on
      mortality, reproductive success or gland expression. To evaluate the quality of
      DNA obtained in natural samples, haemolymph was collected from 187 individuals in
      the field and successfully genotyped at nine microsatellite loci for 95.7% of
      samples. These results indicate that haemolymph-rich defensive secretions contain
      DNA and can be sampled without negative impacts on the health or fitness of
      individual insects.

PMID- 22591241
TI  - Abstracts of the British Association of Urological Surgeons 2012 Annual
      Scientific Meeting. Glasgow, United Kingdom. June 25-28, 2012.

PMID- 22591240
TI  - Induction of apoptosis signaling by glycoprotein of Capsosiphon fulvescens in
      human gastric cancer (AGS) cells.
AB  - Capsosiphon fulvescens is a well-known green sea algae that has been touted in
      recent years as a potential anticancer drug. In this study, C. fulvescens
      glycoprotein (Cf-GP) showed proapoptotic signaling in AGS cells. An MTS assay
      indicated that Cf-GP inhibited the proliferation of AGS cell lines in a dose
      dependent manner. Cells were treated with Cf-GP and the expression of proteins
      associated with apoptosis was examined by Western blotting. Based on the Western
      blot, expression of Cf-GP-activated caspase-cascade and PARP, which is a
      substrate of caspase-3 and -8, and proteins of the Bcl-2 family was observed. Cf
      GP treatment stimulated the release of cytochrome C and apoptotic protease
      activating factor-1 from mitochondria to the cytosol. Cf-GP inhibited the growth
      of AGS cells through induction of sub-G1 phase arrest. We confirmed that sub-G1
      phase arrest was associated with a decrease in the expression of cyclin D, cyclin
      E, Cdk2, Cdk4, and Cdk6, and an increase in the protein levels of p21 and p27. As
      a result, the increased sub-G1 ratio appears to be inhibited by cell
      proliferation. Therefore, we can confirm apoptosis in the AGS cells. Our results
      suggest that Cf-GP could be a potential source of biofunctional material that
      shows anticancer effects in human gastrointestinal cancer.

PMID- 22591242
TI  - The "firework" pattern in dermoscopy.

PMID- 22591243
TI  - Theoretical study on photoisomerization effect with a reversible nonlinear
      optical switch for dithiazolylarylene.
AB  - DFT and TDDFT methods have been performed to investigate the photoisomerization
      effect for dithiazolylarylene on solution. The weak S...N interaction and CH...N
      hydrogen bond restrain the rotation of the side-chain thiazolyl ring in open
      isomer 1a, the higher stability of which prefers to show a high quantum yield of
      photoisomerization. The calculated UV-Vis spectrum at around 320 nm for open
      isomer 1a is bathochromically shifted to 647 nm for closed-isomer 1b, in
      excellent agreement with the experimental photochromic phenomenon. The electron
      transition in ECD (electron circular dichroism) spectra for closed-isomer 1b with
      two chiral carbon atoms is dominated by ICT (intramolecular charge transition)
      and LE (local excitation) corresponding to one positive (440 nm) and one negative
      Cotton effect (650 nm), respectively, where the two chiral carbon atoms play a
      slight role in these transitions. The PES in the S(1) and S(0) states,
      respectively, indicates that the cyclization reaction from open-isomer 1a to
      closed-isomer 1b is allowed in the photoexcited state with high-conversion
      quantum efficiency, while it is forbidden in the thermodynamic process. In
      addition, the second-order nonlinear optical response for closed-isomer 1b is
      nearly six times larger than that for open-isomer 1a. It is also confirmed that
      the photoirradiation evokes the photoisomerization character to show dramatic
      difference in the second-order NLO response, which can be applied to designing
      photochromic materials and reversible NLO switches.

PMID- 22591244
TI  - Bis(allyl)zinc revisited: sigma versus pi bonding of allyl coordination.
AB  - The reinvestigation of two allyl zinc compounds, parent bis(allyl)zinc
      [Zn(C(3)H(5))(2)] (1) and 2-methallyl chloro zinc [Zn(C(4)H(7))Cl] (2), revealed
      two new coordination modes in the solid state for the allyl ligand, viz cis- and
      trans-MU(2)-eta(1):eta(1). These results call for modification of the
      conventional interpretation of zinc-allyl interactions. Computational results
      indicate that the classical eta(3)-bonding mode of the allyl ligand is not
      favored in zinc compounds. A rare case of a zinc-olefin interaction in the dimer
      of [Zn(eta(1)-C(3)H(5))(OC(C(3)H(5))Ph(2))] was found in the monoinsertion
      product of 1 with benzophenone.

PMID- 22591245
TI  - Utilization of smoked salmon trim in extruded smoked salmon jerky.
AB  - During smoked salmon processing, the dark meat along the lateral line is removed
      before packaging; this by-product currently has little economic value. In this
      study, the dark meat trim was incorporated into an extruded jerky. Three
      formulations were processed: 100% smoked trim, 75% : 25% smoked trim : fresh
      salmon fillet, and 50% : 50% smoked trim : fresh salmon blends (w/w basis). The
      base formulation contained salmon (approximately 83.5%), tapioca starch (8%),
      pregelatinized potato starch (3%), sucrose (4%), salt (1.5%), sodium nitrate
      (0.02%), and ascorbyl palmitate (0.02% of the lipid content). Blends were
      extruded in a laboratory-scale twin-screw extruder and then hot-smoked for 5 h.
      There were no significant differences among formulations in moisture, water
      activity, and pH. Protein was highest in the 50 : 50 blend jerky. Ash content was
      highest in the jerky made with 100% trim. Total lipids and salt were higher in
      the 100% trim jerky than in the 50 : 50 blend. Hot smoking did not adversely
      affect docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) content in
      lipids from 100% smoked trim jerky. Servings of salmon jerky made with 75% and
      100% smoked trim provided at least 500 mg of EPA and DHA. The 50 : 50 formulation
      had the highest Intl. Commission on Illumination (CIE) L*, a*, and b* color
      values. Seventy consumers rated all sensory attributes as between "like slightly"
      and "like moderately." With some formulation and processing refinements, lateral
      line trim from smoked salmon processors has potential to be incorporated into
      acceptable, healthful snack products. PRACTICAL APPLICATION: Dark meat along the
      lateral line is typically discarded by smoked salmon processors. This omega-3
      fatty acid rich by-product can be used to make a smoked salmon jerky that
      provides a convenient source of these healthful lipids for consumers.

PMID- 22591246
TI  - Configurations of power relations in the Brazilian emergency care system:
      analyzing a context of visible practices.
AB  - In this paper, we make explicit the changing configurations of power relations
      that currently characterize the Brazilian Emergency Care System (SAMU) team in
      Belo Horizonte, Brazil. The SAMU is a recent innovation in Brazilian healthcare
      service delivery. A qualitative case study methodology was used to explore SAMU's
      current organizational arrangements, specifically the power relations that have
      developed and that demonstrate internal team struggles over space and defense of
      particular occupational interests. The argument advanced in this paper is that
      these professionals are developing their work in conditions of exposure, that is,
      they are always being observed by someone, and that such observational exposure
      provides the conditions whereby everyday emergency care practices are enacted
      such that practice is shaped by, as well as shapes, particular, yet recognizable
      power relationships. Data were collected through the observation of the SAMU's
      work processes and through semi-structured interviews. Research materials were
      analyzed using discourse analysis. In the emergency care process of work,
      visibility is actually embedded in the disciplinary context and can thus be
      analyzed as a technique applied to produce disciplined individuals through the
      simple mechanisms elaborated by Foucault such as hierarchical surveillance,
      normalizing judgment, and the examination. 

PMID- 22591247
TI  - A transatlantic survey of nutrition practice in acute pancreatitis.
AB  - BACKGROUND: Many guidelines exist for the nutritional management of acute
      pancreatitis; however, little is known regarding current practice. We aimed to
      investigate feeding practices, including the use of parenteral/enteral nutrition.
      METHODS: The study design was a cross-sectional, descriptive survey. Electronic
      surveys were sent to dietitians in the UK, the Republic of Ireland and Canada. Of
      253 dietitians surveyed, 204 saw patients with acute pancreatitis regularly or
      occasionally and were included in the analyses. RESULTS: Most dietitians (92.8%)
      considered early feeding to mean <48 h after presentation. Over half (54.2%)
      favoured early feeding in severe disease, less in obesity (42%) and more with pre
      existing malnutrition (81.9%). There was a tendency to feed earlier in university
      hospitals (P = 0.015), especially in obesity (P = 0.011). There was a tendency
      towards enteral (versus parenteral) nutrition in university hospitals (P =
      0.000). The majority preferred the jejunal route (64.2%), although this was lower
      in the UK (43.8%) than in Canada (77.8%) or Ireland (54.2%). Under one-quarter of
      UK dietitians (23.2%) reported the existence of a pancreatic multidisciplinary
      team in their institutions, although this was lower in Ireland and Canada.
      CONCLUSIONS: Despite guidelines, there are gaps in the nutritional management of
      acute pancreatitis, including a continued reliance on parenteral feeding.

PMID- 22591248
TI  - Pincer-ligated nickel hydridoborate complexes: the dormant species in catalytic
      reduction of carbon dioxide with boranes.
AB  - Nickel pincer complexes of the type [2,6-(R(2)PO)(2)C(6)H(3)]NiH (R = (t)Bu, 1a;
      R = (i)Pr, 1b; R = (c)Pe, 1c) react with BH(3).THF to produce borohydride
      complexes [2,6-(R(2)PO)(2)C(6)H(3)]Ni(eta(2)-BH(4)) (2a-c), as confirmed by NMR
      and IR spectroscopy, X-ray crystallography, and elemental analysis. The reactions
      are irreversible at room temperature but reversible at 60  degrees C. Compound 1a
      exchanges its hydrogen on the nickel with the borane hydrogen of 9-BBN or HBcat,
      but does not form any observable adduct. The less bulky hydride complexes 1b and
      1c, however, yield nickel dihydridoborate complexes reversibly at room
      temperature when mixed with 9-BBN and HBcat. The dihydridoborate ligand in these
      complexes adopts an eta(2)-coordination mode, as suggested by IR spectroscopy and
      X-ray crystallography. Under the catalytic influence of 1a-c, reduction of CO(2)
      leads to the methoxide level when 9-BBN or HBcat is employed as the reducing
      agent. The best catalyst, 1a, involves bulky substituents on the phosphorus donor
      atoms. Catalytic reactions involving 1b and 1c are less efficient because of the
      formation of dihydridoborate complexes as the dormant species as well as partial
      decomposition of the catalysts by the boranes.

PMID- 22591249
TI  - Noise-immune cavity-enhanced optical heterodyne detection of HO2 in the near
      infrared range.
AB  - Accurate measurements of the absolute concentrations of radical species present
      in the atmosphere are invaluable for better understanding atmospheric processes
      and their impact on Earth systems. One of the most interesting species is HO(2),
      the hydroperoxyl radical, whose atmospheric daytime levels are on the order of 10
      ppt and whose observation therefore requires very sensitive detection techniques.
      In this work, we demonstrate the first steps toward the application of external
      cavity diode-laser-based noise-immune cavity-enhanced optical heterodyne
      molecular spectroscopy (NICE-OHMS) to the detection of the HO(2) radical in the
      near-infrared range. Measurements of stable species and of HO(2) were made in a
      laboratory setting, and the possibilities of extending the sensitivity of the
      technique to atmospheric conditions are discussed.

PMID- 22591250
TI  - A study evaluating for a threshold effect of alcohol consumption in pregnancy on
      infant physical characteristics ideally has a control group not ingesting
      alcohol.

PMID- 22591251
TI  - The book, the stories, the people: an ongoing dialogic narrative inquiry study
      combining a practice development project. Part 1: the research context.
AB  - This paper, part one of a two paper report, describes key aspects of the research
      context of an ongoing practice development project, conducted on two UK sites.
      The paper begins with a discussion of the project's origins within a community of
      people working in the recovery paradigm, including the contributory strand of the
      first author's recovery and survivor writing. The discussion then turns to three
      inter-related areas within which the research component sits and which provide it
      with philosophical, theoretical and conceptual coherence. Each area will be
      unpacked and its significance explained. This will provide a platform for
      discussing the focus, methodology and methods of the research, and related
      assumptions governing both data collection and analysis. The paper concludes with
      a research commitment to a mental health nursing practice allied to recovery as
      narrative healing. Links are made to the second paper which describes the context
      and specifics of a Writing for Recovery project for users, survivors and carers.
      This shares with, and builds on, the overall project's research context and its
      assumptions.

PMID- 22591252
TI  - Recalcitrant Pseudomonas keratitis after epipolis laser-assisted in situ
      keratomileusis: case report and review of the literature.
AB  - We report a case of recalcitrant microbial keratitis after epipolis laser
      assisted in situ keratomileusis (epi-LASIK) surgery caused by Pseudomonas
      aeruginosa and review the literature on resistant Pseudomonas keratitis after
      excimer laser surgery. Microbial keratitis occurred two weeks after epi-LASIK
      surgery and was resistant to fluoroquinolones, aminoglycosides and macrolides but
      sensitive to meropenem. The patient had total corneal melting and required
      therapeutic penetrating keratoplasty. The globe could be salvaged and the
      distance visual acuity was 6/60 in the right eye. Recalcitrant Pseudomonas
      keratitis might require a therapeutic graft and necessitate the use of
      intravenous meropenem to prevent recurrence of infection.

PMID- 22591253
TI  - Prediction of volume of distribution at steady state in humans: comparison of
      different approaches.
AB  - INTRODUCTION: Reasonable prediction of volume of distribution at steady state
      (Vd(ss)) in humans is required for screening drug candidates, evaluating drug
      safety, and estimating first-in-human doses. AREAS COVERED: This review
      summarizes methods for the prediction of human Vd(ss) and tissue plasma partition
      coefficients (K(p)). The methods reviewed includes allometric scaling,
      physiologically based models, correlation with animal Vd(ss) and in silico
      models. The assumptions, equations, input data required, advantages, and
      limitations of each approach are discussed. Due to the variations among test
      datasets, some studies have reached inconsistent conclusions. Hence, a
      comprehensive comparison of various approaches using a large and exhaustive
      dataset is warranted to address the controversies in human Vd(ss) prediction.
      EXPERT OPINION: Compared with allometric scaling, the Oie-Tozer method and
      correlations between human and animal Vd(ss) are more accurate. All the three
      methods can be used for accurate predictions of human Vd(ss) just prior to first
      in-human studies. Although in vivo animal data are not required, tissue
      composition-based approaches and inter-tissue correlation of K(p) provide
      reasonable predictive accuracies and are promising for physiologically based
      pharmacokinetic modeling. The in silico models are most suitable for high
      throughput screening of compounds, which are at an early stage of development.

PMID- 22591254
TI  - Potent and selective inhibition of magnolol on catalytic activities of UGT1A7 and
      1A9.
AB  - 1. Human exposure to magnolol can reach a high dose in daily life. Our previous
      studies indicated that magnolol showed high affinities to several UDP
      glucuronosyltransferases (UGTs) This study was designed to examine the in vitro
      inhibitory effects of magnolol on UGTs, and further to evaluate the possibility
      of the in vivo inhibition that might happen. 2. Assays with recombinant UGTs and
      human liver microsomes (HLM) indicated that magnolol (10 uM) can selectively
      inhibit activities of UGT1A9 and extra-hepatic UGT1A7. Inhibition of magnolol on
      UGT1A7 followed competitive inhibition mechanism, while the inhibition on UGT1A9
      obeyed either competitive or mixed inhibition mechanism, depending on substrates.
      The K(i) values for UGT1A7 and 1A9 are all in nanomolar ranges, lower than
      possible magnolol concentrations in human gut lumen and blood, indicating the in
      vivo inhibition on these two enzymes would likely occur. 3. In conclusion, UGT1A7
      and 1A9 can be strongly inhibited by magnolol, raising the alarm for safe
      application of magnolol and traditional Chinese medicines containing magnolol.
      Additionally, given that UGT1A7 is an extra-hepatic enzyme, magnolol can serve as
      a selective UGT1A9 inhibitor that will act as a new useful tool in future hepatic
      glucuronidation phenotyping.

PMID- 22591255
TI  - Emergency departments, Medicaid costs, and access to primary care--understanding
      the link.

PMID- 22591256
TI  - Lost in translation--?Como se dice, "Patient Protection and Affordable Care Act"?

PMID- 22591257
TI  - Regulatory review of novel therapeutics--comparison of three regulatory agencies.
AB  - BACKGROUND: The upcoming reauthorization of the Prescription Drug User Fee Act
      focuses on improving the review process for new drug applications at the Food and
      Drug Administration (FDA). METHODS: Using publicly available information from the
      FDA, the European Medicines Agency (EMA), and Health Canada, we compared the time
      for completion of the first review and the total review time for all applications
      involving novel therapeutic agents approved by the three regulatory agencies from
      2001 through 2010 and determined the geographic area in which each novel
      therapeutic agent was first approved for use. RESULTS: There were 510
      applications for novel therapeutic agents approved from 2001 through 2010--225 by
      the FDA, 186 by the EMA, and 99 by Health Canada; among the applications, there
      were 289 unique agents. The median length of time for completion of the first
      review was 303 days (interquartile range, 185 to 372) for applications approved
      by the FDA, 366 days (interquartile range, 310 to 445) for those approved by the
      EMA, and 352 days (interquartile range, 255 to 420) for those approved by Health
      Canada (P<0.001 for the comparison across the three agencies). The median total
      review time was also shorter at the FDA than at the EMA or Health Canada
      (P=0.002). Among the 289 unique novel therapeutic agents, 190 were approved in
      both the United States and Europe (either by the EMA or through the mutual
      recognition process), of which 121 (63.7%) were first approved in the United
      States; similarly, 154 were approved in both the United States and Canada, of
      which 132 (85.7%) were first approved in the United States. CONCLUSIONS: For
      novel therapeutic agents approved between 2001 and 2010, the FDA reviewed
      applications involving novel therapeutics more quickly, on average, than did the
      EMA or Health Canada, and the vast majority of these new therapeutic agents were
      first approved for use in the United States. (Funded by the Pew Charitable
      Trusts.).

PMID- 22591258
TI  - Inhibitory effects of phosphodiesterase 5 inhibitor, tadalafil, on
      mechanosensitive bladder afferent nerve activities of the rat, and on acrolein
      induced hyperactivity of these nerves.
AB  - What's known on the subject? and What does the study add? Tadalafil, a
      phosphodiesterase type 5 inhibitor, might be effective for not only erectile
      dysfunction but also lower urinary tract symptoms (LUTS). One of the mechanisms
      of tadalafil on LUTS is added in the study. OBJECTIVE: To determine if tadalafil,
      a phosphodiesterase type 5 inhibitor, decreases afferent nerve activity from the
      bladder with and without chemical stimulation by intravesical acrolein
      instillation. MATERIALS AND METHODS: Female Sprague-Dawley rats were used. Under
      urethane anaesthesia, single afferent fibres of the nerve primarily originating
      from the bladder were identified by electrical stimulation of the pelvic nerve
      and by bladder distension, and classified by conduction velocity as Adelta- or C
      fibres. After measuring the baseline single afferent activities (SAA) during
      constant filling, two experiments were performed. First, tadalafil was
      administrated intravenously (i.v.) at three doses, 0.01, 0.03 and 0.1 mg/kg
      cumulatively and SAA were repeatedly studied after each administration. Second,
      in the presence of vehicle or tadalafil (0.1 mg/kg) i.v., the effect of
      intravesical instillation of acrolein (0.003%) was studied. RESULTS: In all, 39
      single units were isolated (Adelta-fibres 21; C-fibres, 18) in 25 rats. Tadalafil
      dose-dependently decreased SAA of both Adelta- and C-fibres during saline
      instillation. Intravesical acrolein facilitated SAA of both fibres after vehicle
      administration. Pretreatment with tadalafil significantly inhibited the acrolein
      induced hyperactivity of both fibres. CONCLUSION: Our study shows, using
      selective unifibre potential measurement, that systemic administration of
      tadalafil reduces mechanosensitive afferent activities of both Adelta- and C
      fibres elicited by bladder distension in the rat, and also that tadalafil has an
      inhibitory effect on the increased activities of both fibres induced by
      intravesical acrolein instillation.

PMID- 22591259
TI  - Symmetrical drug-related intertriginous and flexural exanthema caused by
      celecoxib.

PMID- 22591260
TI  - The adjunct effectiveness of diode laser gingivectomy in maintaining periodontal
      health during orthodontic treatment.
AB  - OBJECTIVE: To evaluate the effectiveness of diode laser gingivectomy as an
      adjunct to nonsurgical periodontal treatment in the management of periodontal
      health among patients receiving fixed orthodontic appliance therapy (FOAT).
      MATERIALS AND METHODS: Thirty patients undergoing FOAT with gingival enlargement
      were block randomized into two treatment groups. The test group received diode
      laser gingivectomy (940-nm diode laser, ezlase, Biolase Technology Inc) as an
      adjunct to nonsurgical periodontal treatment. The control group received
      nonsurgical periodontal treatment only. For both groups, five periodontal
      parameters were assessed at baseline, 1 month, 3 months, and 6 months: Plaque
      Index, Gingival Index, bleeding on probing, probing pocket depth, and Gingival
      Overgrowth Index. Intra- and intergroup variations in the periodontal parameters
      were determined over time. RESULTS: Both groups showed statistically significant
      improvements in periodontal health over the study period (P < .05). However,
      significant improvements in periodontal health were evident earlier among the
      test group subjects (P < .05). The magnitude of improvement in periodontal health
      compared to baseline was greater in the test group than in the control group for
      Gingival Overgrowth Index at 1 month (P < .001) and 3 months (P < .05), Gingival
      Index at 3 months (P < .05) and 6 months (P < .05), and probing pocket depth at 1
      month (P < .05). CONCLUSIONS: Nonsurgical periodontal management with or without
      the adjunct use of lasers can be effective in the management of gingival health
      problems among patients receiving FOAT. The adjunctive use of lasers can produce
      an earlier and greater improvement in gingival health.

PMID- 22591261
TI  - Color stability and fluorescence of different orthodontic esthetic archwires.
AB  - OBJECTIVE: To evaluate the color stability of six esthetic archwires at different
      time periods and their fluorescence. MATERIALS AND METHODS: Samples were
      evaluated after 7, 14, and 21 days of immersion in staining solution. Color
      measurements were performed by means of a spectrophotometer according to the
      Commission Internationale de I'Eclairage L*a*b* system, and color changes
      (DeltaE*) and National Bureau of Standards units were computed. The fluorescence
      of as-received samples was evaluated by two observers and compared with that of a
      bovine central incisor. Statistical differences were investigated using analysis
      of variance and Tukey's post hoc test. RESULTS: All brands showed statistically
      significant color change after 21 days (DeltaE* from 1.88 to 12.06). The Optis
      archwire (fiber-reinforced composite) presented the highest color alteration,
      although staining was observed only near its ends. The Trianeiro archwire (coated
      nickel-titanium) and the Ortho Organizers archwire (coated stainless steel)
      presented with less color change. The Optis archwire was the only one that
      presented with fluorescence similar to that of bovine teeth. CONCLUSIONS: All
      esthetic archwires assessed showed clinically noticeable color change after 21
      days in staining solution. The optical properties of currently available esthetic
      archwires may not yet be ideal.

PMID- 22591263
TI  - Characterization of copolymers and blends by quintuple-detector size-exclusion
      chromatography.
AB  - The properties imparted, oftentimes synergistically, by the different components
      of copolymers and blends account for the widespread use of these in a variety of
      industrial products. Most often, however, processing and end-use of these
      materials (especially copolymers) is optimized empirically, due to a lack of
      understanding of the physicochemical phase-space occupied by the macromolecules.
      Here, this shortcoming is addressed via a quintuple-detector size-exclusion
      chromatography (SEC) method consisting of multiangle static light scattering
      (MALS), quasi-elastic light scattering (QELS), differential viscometry (VISC),
      ultraviolet absorption spectroscopy (UV), and differential refractometry (DRI)
      coupled online to the separation method. Applying the SEC/MALS/QELS/VISC/UV/DRI
      method to the study of a poly(acrylamide-co-N,N-dimethylacrylamide) copolymer in
      which both monomer functionalities absorb in the same region of the UV spectrum,
      we demonstrate how to determine the chemical heterogeneity, molar mass averages
      and distribution, and solution conformation of the copolymer all in a single
      analysis. Additionally, through the various mutually independent conformational
      and architectural metrics provided by combining the five detectors, including the
      fractal dimension (derived from two different detector combinations), two
      different dimensionless size parameters, the chemical heterogeneity, and the
      persistence length, it is shown that the monomeric arrangement is more
      alternating than random at lower molar masses, thus causing the copolymer to
      adopt a more extended conformation in solution in this molar mass (M) regime. At
      high M, however, the copolymer is shown to be and to behave more like a random
      coil homopolymer, after passing through a 250 kg mol(-1)-broad region of
      intermediate chain flexibility. Thus, the combination of five detectors provides
      a unique means by which to determine absolute properties of the copolymer,
      solution-specific physical behavior, and the underlying chemical basis of the
      latter. The quintuple-detector method was also extended to the study of blends of
      polyacrylamide and poly(N,N-dimethylacrylamide) homopolymers to quantitate their
      molar mass, solution conformation, and chemical heterogeneity and to shed light
      on the breadth of the distributions of the component species. The method
      presented should be applicable to the study of copolymers and blends in which
      either one or both component moieties or polymers absorb in the UV region and can
      be implemented using not only SEC but other size-based separation methods as
      well.

PMID- 22591264
TI  - Mutual exclusivity in the synthesis of high crystallinity and high yield single
      walled carbon nanotubes.
AB  - We report the mutually exclusive relationship between carbon nanotube (CNT) yield
      and crystallinity. Growth conditions were optimized for CNT growth yield and
      crystallinity through sequential tuning of three input variables: growth enhancer
      level, growth temperature, and carbon feedstock level. This optimization revealed
      that, regardless of the variety of carbon feedstock and growth enhancer, the
      optimum conditions for yield and crystallinity differed significantly with
      yield/crystallinity, preferring lower/higher growth temperatures and higher/lower
      carbon feedstock levels. This mutual exclusivity stemmed from the inherent
      limiting mechanisms for each property.

PMID- 22591262
TI  - Systemic analyses of immunophenotypes of peripheral T cells in non-segmental
      vitiligo: implication of defective natural killer T cells.
AB  - Although it is widely believed that non-segmental vitiligo (NSV) results from the
      autoimmune destruction of melanocytes, a clear understanding of defects in immune
      tolerance, which mediate this uncontrolled self-reactivity, is still lacking. In
      the present study, we systemically evaluated circulating regulatory T (Treg)
      cells, including CD4(+) CD25(+) FoxP3(+)  Treg cells and invariant natural killer
      T (iNKT) cells, as well as naive and memory CD4(+)  and CD8(+)  T cells and their
      cytokine production, in a cohort of 43 progressive NSV patients with race-,
      gender-, and age-matched healthy controls. We found that the general
      immunophenotypes of CD4(+)  and CD8(+)  T cells and the percentage of CD4(+)
      CD25(+) FoxP3(+)  Tregs were comparable between NSV and healthy controls.
      However, percentages of peripheral iNKT cells were significantly decreased in NSV
      patients compared to that in healthy controls. Our data confirm the previous
      notion that the percentage of peripheral CD4(+) CD25(+) FoxP3(+)  Tregs remains
      unaltered in NSV and suggests the involvement of defective iNKT cells in the
      pathogenesis of NSV.

PMID- 22591265
TI  - Formerly known as inhibitory: effects of 1-Hz rTMS on auditory cortex are state
      dependent.
AB  - The major repetitive transcranial magnetic stimulation (rTMS) paradigm applied to
      the treatment of tinnitus has been the 1-Hz variant due to its alleged inhibitory
      effects. Clinical effects have, however, been hampered by great interindividual
      variability as well as the fact that TMS includes no explicit mechanism to
      modulate excitability in circumscribed regions of tonotopically organised
      auditory fields. Following studies showing that the effect of TMS depends on the
      activational state preceding the stimulation, participants were exposed to 10 min
      of either notch- or bandpass-filtered noise prior to 1-Hz rTMS applied to the
      left auditory cortex. A control group was additionally assessed using bandpass
      noise - albeit with subsequent sham stimulation - to assess whether effects were
      due to the differential sounds alone or to a genuine interaction between sound
      and rTMS. Electroencephalogram was recorded from 128 electrodes before and after
      the experimental treatment while participants performed an auditory intensity
      discrimination task. While state-dependency effects from the behavioural data are
      not conclusive, several condition * (sound) frequency effects (some specific to
      the stimulated side) could be observed. Importantly, many of these could not be
      explained by the use of rTMS or the filtered noise alone. The resulting patterns
      are, however, complex and temporally variable, which currently prohibits
      recommendations on how to design a clinically effective approach to treat
      tinnitus. Nevertheless, our study gives the first evidence that state-dependency
      principles can induce sound frequency-specific effects in the auditory cortex,
      providing a crucial proof-of-principle upon which future studies can build.

PMID- 22591266
TI  - Lung transplant infection.
AB  - Lung transplantation has become an accepted therapeutic procedure for the
      treatment of end-stage pulmonary parenchymal and vascular disease. Despite
      improved survival rates over the decades, lung transplant recipients have lower
      survival rates than other solid organ transplant recipients. The morbidity and
      mortality following lung transplantation is largely due to infection- and
      rejection-related complications. This article will review the common infections
      that develop in the lung transplant recipient, including the general risk factors
      for infection in this population, and the most frequent bacterial, viral, fungal
      and other less frequent opportunistic infections. The epidemiology, diagnosis,
      prophylaxis, treatment and outcomes for the different microbial pathogens will be
      reviewed. The effects of infection on lung transplant rejection will also be
      discussed.

PMID- 22591267
TI  - Male quality, signal reliability and female choice: assessing the expectations of
      inter-sexual selection.
AB  - Numerous models have attempted to explain the evolution of extravagant male
      ornaments found in many species. Inter-sexual indicator models postulate that
      male ornaments evolved as signals of quality, and that females use these signals
      to select the highest quality males. These models involve three traits--male
      quality, male signals and female preferences--and have specific expectations
      about the relative strengths of the phenotypic relationships between these
      traits. Using data from anuran species, we assessed the relative strengths of the
      phenotypic relationships using meta-analysis. The relative strengths of these
      phenotypic correlations were as expected by indicator models, providing support
      for indicator models of inter-sexual selection. We also found much variation in
      our data, suggesting that additional, untested factors may mediate inter-sexual
      interactions in this taxon, such as differences in the importance of quality
      signalling between species. These factors require investigation, in order to
      improve our understanding of inter-sexual selection.

PMID- 22591268
TI  - Evaluation of a hand-held far-ultraviolet radiation device for decontamination of
      Clostridium difficile and other healthcare-associated pathogens.
AB  - BACKGROUND: Environmental surfaces play an important role in transmission of
      healthcare-associated pathogens. There is a need for new disinfection methods
      that are effective against Clostridium difficile spores, but also safe and rapid.
      The SterilrayTM Disinfection Wand device is a hand-held room decontamination
      technology that utilizes far-ultraviolet radiation (185-230 nm) to kill
      pathogens. METHODS: We examined the efficacy of disinfection using the Sterilray
      device in the laboratory, in rooms of hospitalized patients, and on surfaces
      outside of patient rooms (i.e. keyboards and portable medical equipment).
      Cultures for C. difficile, methicillin-resistant Staphylococcus aureus (MRSA),
      and vancomycin-resistant Enterococcus (VRE) were collected from commonly-touched
      surfaces before and after use of the Sterilray device. RESULTS: On inoculated
      surfaces in the laboratory, application of the Sterilray device at a radiant dose
      of 100 mJ/cm(2) for ~ 5 seconds consistently reduced recovery of C. difficile
      spores by 4.4 CFU log10, MRSA by 5.4 log(10)CFU and of VRE by 6.9 log10CFU. A >3
      log10 reduction of MRSA and VRE was achieved in ~2 seconds at a lower radiant
      dose, but killing of C. difficile spores was significantly reduced. On keyboards
      and portable medical equipment that were inoculated with C. difficile spores,
      application of the Sterilray device at a radiant dose of 100 mJ/cm(2) for ~ 5
      seconds reduced contamination by 3.2 log10CFU. However, the presence of organic
      material reduced the lethal effect of the far-UV radiation. In hospital rooms
      that were not pre-cleaned, disinfection with the Sterilray device significantly
      reduced the frequency of positive C. difficile and MRSA cultures (P =0.007).
      CONCLUSIONS: The SterilrayTM Disinfection Wand is a novel environmental
      disinfection technology that rapidly kills C. difficile spores and other
      healthcare-associated pathogens on surfaces. However, the presence of organic
      matter reduces the efficacy of far-UV radiation, possibly explaining the more
      modest results observed on surfaces in hospital rooms that were not pre-cleaned.

PMID- 22591270
TI  - Medical management of ectopic pregnancy: a 10-year case series.
AB  - AIMS: The study was concerned with the medical management of ectopic pregnancy;
      specifically, (i) whether there is a significant increase in follow-up duration
      when the serum betahCG is greater than 3000 iu/l and (ii) an association between
      the serum betahCG concentration at presentation and the need for a repeat dose of
      Methotrexate and/or emergency surgical intervention, and if so, to try to
      quantify the probability of the requirement for either a repeat dose or surgery
      depending on serum betahCG concentration. METHODS: A retrospective case note
      review of all medically treated ectopic pregnancies over a 10-year period in a
      tertiary referral hospital in the southwest of England. RESULTS: 398 women were
      identified in total. Three were excluded and five case notes could not be
      located. A betahCG <= 3000 iu/l occurred in 73.8%. Mean follow-up duration was
      25.9 days when the betahCG was <= 3000 iu/l compared to 42.3 days when it was
      >3000 iu/l. When betahCG was <= 3000 iu/l, a repeat dose of Methotrexate and
      emergency surgery were required in 10.4 and 4.5% cases, respectively, compared to
      21.6 and 14.7% when betahCG >3000 iu/l. All differences were statistically
      significant. By fitting logistic regression models to our data, a reference table
      indicating the risk of requiring a repeat dose of Methotrexate or subsequent
      surgery for any betahCG level has been created. CONCLUSIONS: Although follow-up
      duration and the need for repeat doses of Methotrexate and/or surgical
      intervention increases with increasing serum betahCG, medical management is still
      safe and effective when the betahCG is >3000 iu/l and should be promoted.

PMID- 22591271
TI  - Evaluation of preservative efficacy in pharmaceutical products: the use of
      psychrotolerant, low-nutrient preferring microbes in challenge tests.
AB  - WHAT IS KNOWN AND OBJECTIVE: Preservative efficacy in medicines is typically
      investigated using challenge tests. In such tests, the product is artificially
      contaminated with a high concentration of standard bacterial and fungal test
      strains such as Pseudomonas aeruginosa and Candida albicans. The rate and extent
      of reductions in inoculum viability over a specified period forms the basis for
      acceptance/rejection of preservative efficacy. None of the strains named for
      inclusion in the challenge test outlined in the European Pharmacopoeia are
      associated with the contamination of high-quality water used in pharmaceutical
      production. Alpha- and Betaproteobacteria are easily the most common microbes in
      waters intended for pharmaceutical production. In addition, none of the standard
      test strain panel prefer low-nutrient, dilute conditions or grow at or around
      refrigeration temperatures. This is important because the water activity and
      nutrient content of medicines can vary greatly and medicines are often stored
      cold. We investigate the relevance of these factors when testing preservative
      efficacy by including other strains in challenge tests. METHODS: Psychrotolerant,
      low-nutrient preferring strains (Beta- and Alphaproteobacteria and a yeast) were
      isolated from pristine waters. These were compared in challenge tests with C.
      albicans and P. aeruginosa using different storage temperatures. Pharmaceutical
      products differing widely in water-content, pH and preservative systems were
      included in the study. RESULTS AND DISCUSSION: Regardless of the type of medicine
      tested C. albicans always showed superior survival characteristics to the yeast
      isolate (Cryptococcus terricola). One of the three screened bacterial strains (a
      Sphingomonas sp.) survived significantly better than P. aeruginosa in all but one
      product tested. However, the results for all products taken together cannot
      easily be explained by reference to this strain's psychrotolerancy or its
      preference for dilute, low-nutrient environments. This study supports previous
      work indicating that the inclusion of wild-type test strains, in this instance
      strains that are suited to survival in high-quality waters, improves preservative
      efficacy tests. WHAT IS NEW AND CONCLUSION: Use of a Sphingomonas sp. isolated
      from a pristine water as a challenge test strain, gave a more stringent
      indication of preservative efficacy in a wide range of pharmaceuticals than did
      P. aeruginosa.

PMID- 22591269
TI  - The combination of quantitative PCR and western blot detecting CP4-EPSPS
      component in Roundup Ready soy plant tissues and commercial soy-related
      foodstuffs.
AB  - With the widespread use of Roundup Ready soy (event 40-3-2) (RRS), the
      comprehensive detection of genetically modified component in foodstuffs is of
      significant interest, but few protein-based approaches have been found useful in
      processed foods. In this report, the combination of quantitative PCR (qPCR) and
      western blot was used to detect cp4-epsps gene and its protein product in
      different RRS plant tissues and commercial soy-containing foodstuffs. The foods
      included those of plant origin produced by different processing procedures and
      also some products containing both meat and plant protein concentrates. The
      validity of the 2 methods was confirmed first. We also showed that the CP4-EPSPS
      protein existed in different RRS plant tissues. In certain cases, the results
      from the western blot and the qPCR were not consistent. To be specific, at least
      2 degraded fragments of CP4-EPSPS protein (35.5 and 24.6 kDa) were observed. For
      dried bean curd crust and deep-fried bean curd, a degraded protein fragment with
      the size of 24.6 kDa appeared, while cp4-epsps gene could not be traced by qPCR.
      In contrast, we found a signal of cp4-epsps DNA in 3 foodstuffs, including soy
      containing ham cutlet product, meat ball, and sausage by qPCR, while CP4-EPSPS
      protein could not be detected by western blot in such samples. Our study
      therefore concluded that the combination of DNA- and protein-based methods would
      compensate each other, thus resulting in a more comprehensive detection from
      nucleic acid and protein levels. PRACTICAL APPLICATION: The combination of
      quantitative PCR (qPCR) and western blot was used to detect cp4-epsps gene and
      its protein product in different Roundup Ready soy (event 40-3-2) plant tissues
      and commercial soy-containing foodstuffs. The foods included those of plant
      origin produced by different processing procedures and also some products
      containing a combination of both meat and plant protein concentrates. This study
      indicated that the combination of DNA- and protein-based methods would supplement
      each other for genetically modified detection from nucleic acid and protein
      levels. Accordingly, qPCR and western blot could be used in CP4-EPSPS detection
      in a wide variety of soy-related foodstuffs.

PMID- 22591272
TI  - Fluoride-ion acceptor properties of WSF4: synthesis, characterization, and
      computational study of the WSF5(-) and W2S2F9(-) anions and 19F NMR spectroscopic
      characterization of the W2OSF9(-) anion.
AB  - The new [N(CH(3))(4)][WSF(5)] salt was synthesized by two preparative methods:
      (a) by reaction of WSF(4) with [N(CH(3))(4)][F] in CH(3)CN and (b) directly from
      WF(6) using the new sulfide-transfer reagent [N(CH(3))(4)][SSi(CH(3))(3)]. The
      [N(CH(3))(4)][WSF(5)] salt was characterized by Raman, IR, and (19)F NMR
      spectroscopy and [N(CH(3))(4)][WSF(5)].CH(3)CN by X-ray crystallography. The
      reaction of WSF(4) with half an aliquot of [N(CH(3))(4)][F] yielded
      [N(CH(3))(4)][W(2)S(2)F(9)], which was characterized by Raman and (19)F NMR
      spectroscopy and by X-ray crystallography. The WSF(5)(-) and W(2)S(2)F(9)(-)
      anions were studied by density functional theory calculations. The novel
      [W(2)OSF(9)](-) anion was observed by (19)F NMR spectroscopy in a CH(3)CN
      solution of WOF(4) and WSF(5)(-), as well as CH(3)CN solutions of WSF(4) and
      WOF(5)(-).

PMID- 22591273
TI  - Optical performance comparison of deflectable laparoscopes for laparoendoscopic
      single-site surgery.
AB  - BACKGROUND AND PURPOSE: Flexible working angles and fine optical visualization
      are major requisite factors in performing laparoendoscopic single-site (LESS)
      urologic procedures. Multiple mechanical design approaches have been used to
      develop deflectable laparoscopes for LESS procedures. We compared the optical
      characteristics of three such devices using a bench top approach to simulate LESS
      in straight and deflected positions. MATERIALS AND METHODS: A 10-mm fixed-rod
      rotating lens device (Storz EndoCameleon) and two 5-mm articulating devices
      (Olympus EndoEye and Stryker IdealEye) were compared using standard industry
      testing protocols for image resolution (United States Air Force-1951 test
      target), distortion (multifrequency grid distortion target), and color
      reproducibility (Gretag Macbeth color checker). RESULTS: The 10-mm fixed-rod
      rotating lens system demonstrated the highest image resolution (5.04 line
      pairs/mm), but also the highest distortion (22.8%). Among the 5-mm flexible
      articulating laparoscopes, resolution was superior with the Olympus EndoEye (4.00
      line pairs/mm) compared with the Stryker IdealEye (3.17 line pairs/mm).
      Distortion (7.0%) and color reproduction (1.18) were superior with the IdealEye
      vs the EndoEye (18.8 %, 1.27). Laparoscope deflection resulted in attenuation of
      resolution by 11% with both articulating models, but not with the fixed rod
      system. CONCLUSIONS: Definition of these optical characteristics may inform
      further development and selection of laparoscopic systems optimized for LESS
      surgery. A narrow but flexible camera can be crucial in the limited working space
      available during these procedures. Further investigation is warranted to
      determine if these objective findings translate into improved surgeon
      performance.

PMID- 22591274
TI  - Strategic direction or operational confusion: level of service user involvement
      in Irish acute admission unit care.
AB  - Mental health care in Ireland has been in the midst of a modernization of
      services since the mid 1980s. Embellished in this change agenda has been the need
      for better care and services with a particular emphasis on greater levels of user
      involvement. Acute admission units provide a setting for mental health care to be
      delivered to people who are unable to be cared for in a community setting.
      Through discussion of findings from semi-structured telephone interviews with 18
      acute admission unit staff nurses, the aim of this paper is to explore the level
      of involvement service users have in acute unit care in Ireland. Reporting on one
      qualitative component of a larger mixed method study, findings will show that
      acute admission unit staff nurses generally involve service users in their care
      by facilitating their involvement in the nursing process, interacting with them
      regularly and using different communication approaches. However, participants
      identified barriers to service user involvement, such as growing administrative
      duties. It can tentatively be claimed that, within an Irish context, acute
      admission unit service users are involved in their care and are communicated with
      in an open and transparent way.

PMID- 22591275
TI  - Multifluorescently traceable nanoparticle by a single-wavelength excitation with
      color-related drug release performance.
AB  - Monodisperse and nanometer-sized periodic mesoporous organosilicas co-doped with
      fluorescence resonance energy transfer cascades composed of triple fluorophores
      at various ratios were prepared. These nanoparticles exhibit multifluorescent
      emissions by a single-wavelength excitation and were designed for the application
      as multichannelly traceable drug carriers. Different from the hydrophilic
      framework of inorganic mesoporous silica and hydrophobic framework of mesoporous
      carbon, these multifluorescent nanoparticles have intrinsically different and
      finely tunable pore surface polarities governed by the type and amount of
      fluorophore inside the framework. When applied as drug carriers, they can achieve
      synchronous or asynchronous release of different drugs by simply choosing
      different colored nanoparticles. These colorful mesoporous composites with finely
      tunable color-related drug release performance provide a strong barcoding system
      for the potential applications of fluorescent nanoparticles in effective
      screening of drugs and therapeutic protocols for diseases.

PMID- 22591276
TI  - Senescence-induced iron mobilization in source leaves of barley (Hordeum vulgare)
      plants.
AB  - * Retranslocation of iron (Fe) from source leaves to sinks requires soluble Fe
      binding forms. As much of the Fe is protein-bound and associated with the leaf
      nitrogen (N) status, we investigated the role of N in Fe mobilization and
      retranslocation under N deficiency- vs dark-induced leaf senescence. * By
      excluding Fe retranslocation from the apoplastic root pool, Fe concentrations in
      source and sink leaves from hydroponically grown barley (Hordeum vulgare) plants
      were determined in parallel with the concentrations of potential Fe chelators and
      the expression of genes involved in phytosiderophore biosynthesis. * N supply
      showed opposing effects on Fe pools in source leaves, inhibiting Fe export out of
      source leaves under N sufficiency but stimulating Fe export from source leaves
      under N deficiency, which partially alleviated Fe deficiency-induced chlorosis.
      Both triggers of leaf senescence, shading and N deficiency, enhanced
      NICOTIANAMINE SYNTHASE2 gene expression, soluble Fe pools in source leaves, and
      phytosiderophore and citrate rather than nicotianamine concentrations. * These
      results indicate that Fe mobilization within senescing leaves is independent of a
      concomitant N sink in young leaves and that phytosiderophores enhance Fe
      solubility in senescing source leaves, favoring subsequent Fe retranslocation.

PMID- 22591277
TI  - Variability in step training enhances locomotor recovery after a spinal cord
      injury.
AB  - Performance of a motor task is improved by practicing a specific task with added
      'challenges' to a training regimen. We tested the hypothesis that, in the absence
      of brain control, the performance of a motor task is enhanced by training using
      specific variations of that task. We utilized modifications of step performance
      training to improve the ability of spinal rats to forward step. After a complete
      thoracic spinal cord transection, 20 adult rats were divided randomly to
      bipedally step on a treadmill in the forward, sideward, or backward direction for
      28 sessions (20 min, 5 days/week) and subsequently tested for their ability to
      step in the forward direction. Although the animals from all trained groups
      showed improvement, the rats in the sideward-trained and backward-trained groups
      had greater step consistency and coordination along with higher peak amplitudes
      and total integrated activity of the rectified electromyographic signals from
      selected hindlimb muscles per step during forward stepping than the rats in the
      forward-trained group. Our results demonstrate that, by retaining the fundamental
      features of a motor task (bipedal stepping), the ability to perform that motor
      task can be enhanced by the addition of specific contextual variations to the
      task (direction of stepping). Our data suggest that the forward stepping neuronal
      locomotor networks are partially complemented by synchronous activation of
      interneuronal/motoneuronal populations that are also a part of the sideward or
      backward stepping locomotor networks. Accordingly, the overlap and interaction of
      neuronal elements may play a critical role in positive task transference.

PMID- 22591278
TI  - Dietary vitamin D3 supplementation at 10* the adequate intake improves functional
      capacity in the G93A transgenic mouse model of ALS, a pilot study.
AB  - BACKGROUND: Vitamin D has antioxidant, anti-inflammatory, and neuroprotective
      properties, and may mitigate amyotrophic lateral sclerosis (ALS) pathology. AIMS:
      To determine the effects of dietary vitamin D(3) (D(3)) at 10-fold the adequate
      intake (AI) on functional and disease outcomes and lifespan in the transgenic
      G93A mouse model of ALS. METHODS: Starting at age 40 days, 32 G93A mice (21 M, 11
      F) were provided ad libitum with either an adequate (AI; 1 IU/g feed) or high
      (HiD; 10 IU/g feed) D(3) diet. Differences were considered significant at P<=
      0.10, as this was a pilot study. RESULTS: For paw grip endurance, HiD mice had a
      7% greater score between 60-133 d versus AI mice (P= 0.074). For motor
      performance, HiD mice had a 22% greater score between 60-133 days (P= 0.074)
      versus AI mice due to changes observed in male mice, where HiD males had a 33%
      greater score (P= 0.064) versus AI males. There were no significant diet
      differences in disease onset, disease progression, or lifespan. CONCLUSION:
      Although disease outcomes were not affected, D(3) supplementation at 10-fold the
      AI improved paw grip endurance and motor performance in the transgenic G93A mouse
      model of ALS, specifically in males.

PMID- 22591279
TI  - Oxidative stress-mediated apoptotic death in human peripheral blood lymphocytes
      treated with plasma from gamma-irradiated blood.
AB  - The present study is aimed to investigate the effect of plasma from irradiated
      human blood on the induction of apoptotic death in human peripheral blood
      lymphocytes. Our results showed that plasma obtained from gamma-irradiated human
      blood showed a significant decrease in viability and an increase in apoptotic
      death in unirradiated lymphocytes, which is correlated with increase in
      intracellular reactive oxygen species level. Moreover, a decrease in the activity
      of superoxide dismutase in lymphocytes further seems to be associated with
      oxidative stress-mediated apoptotic death. The diffusible factors from irradiated
      blood were found to be generated from the cellular components of blood. Based on
      our results, we suggest induction of oxidative stress-mediated apoptotic death in
      unirradiated lymphocytes by diffusible factors from irradiated blood.

PMID- 22591280
TI  - Histopathological, enzymatic, and molecular alterations induced by cigarette
      smoke inhalation in the pulmonary tissue of mice and its amelioration by aqueous
      Azadirachta indica leaf extract.
AB  - The modulatory and protective effects of aqueous Azadirachta indica leaf extract
      (AAILE) had been investigated against cigarette smoke-induced pulmonary oxidative
      stress and risk of lung cancer. Male Balb/c mice were divided in 4 groups:
      control, cigarette smoke (CS), AAILE, and AAILE + CS. Animals in the CS group
      were exposed to cigarette smoke for a period of 10 weeks. AAILE oral
      administration at a dosage of 100 mg/kg body weight was started 2 weeks prior to
      CS exposure and continued until the termination of the experiment. The pulmonary
      tissue was analyzed for molecular changes and assessed for the risk of lung
      cancer and status of pulmonary detoxification enzymes. An increase in CH2/CH3 and
      decrease in PO2/amide II observed in Fourier transform infrared spectrometry
      correlated well with acute inflammation, infiltration, and lipid peroxidation
      levels observed in histopathological studies and malionaldehyde levels in mice
      exposed to CS. No change was observed in the amide I:amide II ratio. The subtle
      balance between carcinogen activation and detoxification was found to be
      derailed, and it was manifested as a 1.5-times increase in the risk of developing
      lung cancer in the CS-exposed group. However, these changes seemed to normalize
      upon AAILE supplementation.

PMID- 22591281
TI  - Effects of testosterone propionate on oxidative stress and the expression of
      spleen cytokine genes in endosulfan-treated mice.
AB  - The purpose of this research was to investigate the effects of testosterone
      propionate on oxidative stress and cytokine gene expression in endosulfan-treated
      mice. The levels of endosulfan and testosterone propionate were 0 and 0 mg x kg-1
      x d(-1) (control group), 0.8 and 0 mg x kg-1 x d(-1) (endosulfan-treated group),
      and 0.8 and 10 mg x kg(-1) x d(-1) (experimental group), respectively. The
      results showed that total antioxidation capability (T-AOC) in the endosulfan
      treated group was reduced significantly when compared with the control group,
      whereas the levels of malondialdehyde (MDA) and hydroxyl free radicals increased
      when compared with the control group. T-AOC levels in the experimental group were
      higher than that of the endosulfan-treated group, and the levels of MDA and
      hydroxyl free radicals decreased when compared with the endosulfan-treated group.
      The messenger RNA (mRNA) levels of interleukin (IL)-2 and IL-6 in the endosulfan
      treated group were significantly higher than that of the control group. The mRNA
      levels of IL-6 in the experimental group were lower than that of the endosulfan
      treated group, whereas the mRNA levels of IL-2 and interferon-gamma had no
      significant difference between the 2 groups. The results suggest that
      testosterone propionate alleviates oxidative stress induced by endosulfan and at
      least partially reverses the changes of cytokine gene expression in mice. It is
      possible that androgens affect cytokine expression by alleviating oxidative
      stress induced by endosulfan.

PMID- 22591282
TI  - Nuclear factor kappa B: a pro-inflammatory, transcription factor-mediated
      signalling pathway in lung carcinogenesis and its inhibition by nonsteroidal anti
      inflammatory drugs.
AB  - 9,10-Dimethyl benz(a)anthracene (DMBA), when injected intratracheally once at a
      dose of 20 mg/kg body weight, is found to induce lung cancer in rats. Two
      nonsteroidal anti-inflammatory drugs (NSAIDs), indomethacin and etoricoxib, are
      given orally daily as chemopreventive agents at a dose of 0.6 mg/kg body weight
      and 2 mg/kg body weight, respectively, along with DMBA. Morphologic and
      histologic analysis revealed the occurence of tumors and intense cellular
      proliferation in the DMBA-treated animals, whereas no such features were observed
      in the other groups. Nuclear factor kappaB, a nuclear transcription factor, and
      proliferating cell nuclear antigen, a cell proliferation antigen, were studied by
      immunoblotting and immunohistochemistry and their levels were markedly elevated
      in the DMBA group compared with the others. Oxidative stress parameters, as
      studied by the inducible nitric oxide synthase activity, and the levels of
      reactive oxygen and nitrogen species were found to be suppressed in the DMBA
      group. Furthermore, fluorescent staining of the isolated lung cells from
      bronchoalveolar lavage was performed to study apoptosis and alterations in the
      mitochondrial membrane potential, and the DMBA-induced lung cancer was found to
      be associated with high inner mitochondrial membrane potential and a suppressed
      level of apoptosis.

PMID- 22591283
TI  - Evidence of antiapoptotic properties of Pleurotus florida lectin against chronic
      arsenic toxicity in renal cells of rats.
AB  - Chronic arsenic exposure results in toxicity in humans and causes many
      toxicologic manifestations. Apoptosis was measured by cell adhesion, morphologic
      alterations, cell proliferation, terminal deoxyuridine triphosphate nick-end
      labeling (TUNEL), and caspase-3/CPP32 fluorometric protease assay. Results of the
      present study suggested that arsenic administration in rats caused apoptosis by
      elevating morphologic alterations, TUNEL-positive nuclei, caspase-3 activity, and
      DNA damage and by reducing cell adhesion and cell proliferation in a time
      dependent manner. The apoptosis in renal cells of arsenic-exposed rats reverted
      to normal values after coadministration of mushroom lectin. This study provided
      significant evidence that Pleurotus florida lectin has an antiapoptotic property
      by protecting from arsenic-induced toxicity. The beneficial effect of Pleurotus
      florida lectin was proportional to its duration of exposure. This finding might
      be of therapeutic benefit in people suffering from chronic exposure to arsenic
      from natural sources, a global problem that is especially relevant to millions of
      people on the Indian subcontinent.

PMID- 22591285
TI  - Dose-dependent effects of ethanol on lead-induced oxidative stress in rats.
AB  - This study explored the dose-dependent effects of ethanol ingestion during co
      exposure with lead in rats. Lead was administered orally, once daily at a dose of
      10 mg/kg whereas ethanol was given in drinking water at 3 different doses: 1%,
      2%, and 5% along with lead. The exposure continued for 3 months, after which the
      animals were decapitated and various biochemical assays were carried out. The
      results show increased oxidative stress in animals co-exposed to lead and ethanol
      compared with either lead or ethanol alone. A significant decrease in blood delta
      aminolevulinic acid dehydratase activity, glutathione (GSH), GSH peroxidase,
      adenosine triphosphatase, and catalase but a significant increase in reactive
      oxygen species, oxidized GSH, thiobarbituric acid reactive substance, and
      intracellular calcium was noted in lead and ethanol co-exposed animals. The
      changes were found to be dose dependent in lead plus ethanol exposed animals.
      Decrease in glucose-6-phosphate dehydrogenase activity in blood was noted, with
      no significant changes in liver and kidney. Aldehyde dehdrogenase activity
      decreased significantly in animals exposed to either lead or ethanol but a
      pronounced depletion was seen in rats co-exposed to lead and ethanol (5%). The
      results suggest that the combined exposure to lead and ethanol leads to increased
      oxidative stress and possible initiation of apoptosis in rats.

PMID- 22591284
TI  - Photochemical internalization-mediated delivery of chemotherapeutic agents in
      human breast tumor cell lines.
AB  - Breast-conservation surgery (BCS) is now utilized in patients with stage I and II
      invasive breast cancer. However, positive surgical margins are associated with
      recurrence, and therefore some form of localized postoperative therapy
      (radiation/chemotherapy) is necessary to eliminate remaining cancer cells.
      Existing modalities have significant treatment-limiting side effects; therefore,
      alternative forms of localized therapy need to be explored. We studied the ex
      vivo effects of photochemical internalization (PCI) using 4 chemotherapeutic
      agents: cisplatin, cisplatin analog [D prostanoid, DP], doxorubicin, and
      bleomycin) on 3 breast cancer cell lines: MCF-7, MDA-MB-435, and MDA-MB-231.
      Illumination was carried out using a 670-nm diode laser at 5 mW/cm2 following
      incubation in the photosensitizer with aluminum phthalocyanine disulfonate.
      Toxicity was investigated using colony-forming assays and the mechanism of cell
      death was determined using Annexin flow-cytometry. We found that toxicity of DP
      and bleomycin was significantly enhanced by PCI compared with drug alone but was
      unchanged for cisplatin and doxorubicin. PCI treatment caused a decrease in the
      percentage of viable cells, predominantly by enhancing apoptosis. The action was
      synergistic across all 3 cell lines tested for DP and bleomycin. Thus, with
      appropriate delivery devices and choice of chemotherapeutic agents, PCI holds the
      promise of enhancing tumor cell toxicity surrounding the cavity of BCS resection
      sites and thereby decreasing local recurrence.

PMID- 22591286
TI  - Bacillus thuringiensis parasporal proteins induce cell-cycle arrest and caspase
      dependant apoptotic cell death in leukemic cells.
AB  - Bacillus thuringiensis (Bt) parasporal proteins with selective anticancer
      activity have recently garnered interest. This study determines the efficacy and
      mode of cell death of Bt 18 parasporal proteins against 3 leukemic cell lines
      (CEM-SS, CCRF-SB and CCRF-HSB-2).Cell-based biochemical analysis aimed to
      determine cell viability and the percentage of apoptotic cell death in treated
      cell lines; ultrastructural analysis to study apoptotic changes and Western blot
      to identify the parasporal proteins' binding site were performed. Bt 18
      parasporal proteins moderately decreased viability of leukemic cells but not that
      of normal human T lymphocytes. Further purification of the proteins showed
      changes in inhibition selectivity. Phosphatidylserine externalization, active
      caspase-3, cell cycle, and ultrastructural analysis confirmed apoptotic activity
      and S-phase cell-cycle arrest. Western blot analysis demonstrated glyceraldehyde
      3-phosphate dehydrogenase as a binding protein. We suggest that Bt 18 parasporal
      proteins inhibit leukemic cell viability by cell-cycle arrest and apoptosis and
      that glyceraldehyde 3-phosphate dehydrogenase binding initiates apoptosis.

PMID- 22591287
TI  - Implications of climate change (global warming) for the healthcare system.
AB  - WHAT IS KNOWN AND OBJECTIVE: Temperature-sensitive pathogenic species and their
      vectors and hosts are emerging in previously colder regions as a consequence of
      several factors, including global warming. As a result, an increasing number of
      people will be exposed to pathogens against which they have not previously needed
      defences. We illustrate this with a specific example of recent emergence of
      Cryptococcus gattii infections in more temperate climates. COMMENT: The outbreaks
      in more temperate climates of the highly virulent--but usually tropically
      restricted--C. gattii is illustrative of an anticipated growing challenge for the
      healthcare system. There is a need for preparedness by healthcare professionals
      in anticipation and for management of such outbreaks, including other infections
      whose recent increased prevalence in temperate climates can be at least partly
      associated with global warming. WHAT IS NEW AND CONCLUSION: (Re)emergence of
      temperature-sensitive pathogenic species in more temperate climates will present
      new challenges for healthcare systems. Preparation for outbreaks should precede
      their occurrence.

PMID- 22591288
TI  - Therapy-related acute myeloid leukemia (t-AML) with poor-risk cytogenetics in two
      patients with persistent molecular complete remission of acute promyelocytic
      leukemia.
AB  - Therapy-related acute myeloid leukemia (t-AML) is a clinical syndrome occurring
      as a complication after cytotoxic and/or radiation therapy. The incidence of t
      AML after acute promyelocytic leukemia (APL), all-transretinoic acid (ATRA), and
      anthracycline-based therapy is rather low. However, because of the high remission
      rates and long-term overall survival achieved with current APL treatments, late
      complications related to antileukemic therapy should be taken into account,
      giving priority to efficacy agents with the lowest potential of leukemogenesis,
      despite individual genetic susceptibilities that are not well known. Here, we
      report two cases of t-AML observed in two young women who achieved a rapid,
      complete molecular remission (CMR) of APL and who were still in CMR when t-AML
      was diagnosed. These t-AMLs shared some clinical and biological features such as
      poor-risk cytogenetics and a rapidly progressing, unfavorable outcome.
      Retrospective RT-PCR WT1 expression from the onset of APL to t-AML diagnosis did
      not prove to be a good marker for t-AML development.

PMID- 22591289
TI  - Simultaneous up-regulation of matrix metalloproteinases 1, 2, 3, 7, 8, 9 and
      tissue inhibitors of metalloproteinases 1, 4 in serum of patients with chronic
      obstructive pulmonary disease.
AB  - BACKGROUND AND OBJECTIVE: Matrix metalloproteinases (MMP) and tissue inhibitors
      of metalloproteinases (TIMP) have been implicated in chronic obstructive
      pulmonary disease (COPD) pathogenesis. However, the majority of studies have
      focused on single MMP, and there is limited information on parallel expression of
      MMP and their antagonists TIMP. We, therefore, investigated the serum profile of
      MMP 1-3, 7-9, 12 and 13, and TIMP 1-4 in COPD patients. METHODS: Serum MMP 1-3, 7
      9, 12 and 13, and TIMP 1-4 were measured in 74 COPD patients and 20 control
      subjects by multiple microsphere technology. RESULTS: MMP 1-3 and MMP 7-9 were
      elevated in COPD patients compared with control subjects (P= 0.001-0.043). The
      increased concentrations of MMP 1, 8 and 9 paralleled GOLD stage (P= 0.002
      0.007). TIMP 1 and 4 concentrations were elevated in COPD (P < 0.001). MMP 1, 8
      and 9, and TIMP 1 and 4 serum levels in COPD non-smokers were higher than in
      control non-smokers (P = 0.002-0.025). MMP 12 and 13 levels were undetectable in
      our serum samples. CONCLUSIONS: This study provides further evidence for
      increased MMP 1, 7-9, and TIMP 1 serum levels in COPD, and demonstrates for the
      first time serum elevation of MMP 2 and 3, and TIMP 4. The finding that
      circulating TIMP 4 levels are increased in COPD and the observed relationship
      between serum levels of MMP 1, 8 and 9, and GOLD stage requires verification in
      an expanded patient cohort.

PMID- 22591290
TI  - The evolving primary care physician.

PMID- 22591291
TI  - Mental illness--comprehensive evaluation or checklist?

PMID- 22591292
TI  - Grief, depression, and the DSM-5.

PMID- 22591293
TI  - Risk of natalizumab-associated progressive multifocal leukoencephalopathy.
AB  - BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is associated with
      natalizumab treatment. We quantified the risk of PML in patients with multiple
      sclerosis, according to the presence or absence of three risk factors: positive
      status with respect to anti-JC virus antibodies, prior use of immunosuppressants,
      and increasing duration of natalizumab treatment. METHODS: We used data from
      postmarketing sources, clinical studies, and an independent Swedish registry to
      estimate the incidence of PML among natalizumab-treated patients with multiple
      sclerosis, according to positive or negative status with respect to anti-JC virus
      antibodies, prior or no prior use of immunosuppressants, and duration of
      treatment (1 to 24 months vs. 25 to 48 months). Blood samples were available for
      anti-JC virus antibody testing from 5896 patients with multiple sclerosis and
      from 54 patients with multiple sclerosis who were treated with natalizumab and in
      whom PML later developed. RESULTS: As of February 29, 2012, there were 212
      confirmed cases of PML among 99,571 patients treated with natalizumab (2.1 cases
      per 1000 patients). All 54 patients with PML for whom samples were available
      before the diagnosis were positive for anti-JC virus antibodies. When the risk of
      PML was stratified according to three risk factors, the risk of PML was lowest
      among the patients who were negative for anti-JC virus antibodies, with the
      incidence estimated to be 0.09 cases or less per 1000 patients (95% confidence
      interval [CI], 0 to 0.48). Patients who were positive for anti-JC virus
      antibodies, had taken immunosuppressants before the initiation of natalizumab
      therapy, and had received 25 to 48 months of natalizumab treatment had the
      highest estimated risk (incidence, 11.1 cases per 1000 patients [95% CI, 8.3 to
      14.5]). CONCLUSIONS: Positive status with respect to anti-JC virus antibodies,
      prior use of immunosuppressants, and increased duration of natalizumab treatment,
      alone or in combination, were associated with distinct levels of PML risk in
      natalizumab-treated patients with multiple sclerosis. (Funded by Biogen Idec and
      Elan Pharmaceuticals.).

PMID- 22591294
TI  - Azithromycin and the risk of cardiovascular death.
AB  - BACKGROUND: Although several macrolide antibiotics are proarrhythmic and
      associated with an increased risk of sudden cardiac death, azithromycin is
      thought to have minimal cardiotoxicity. However, published reports of arrhythmias
      suggest that azithromycin may increase the risk of cardiovascular death. METHODS:
      We studied a Tennessee Medicaid cohort designed to detect an increased risk of
      death related to short-term cardiac effects of medication, excluding patients
      with serious noncardiovascular illness and person-time during and shortly after
      hospitalization. The cohort included patients who took azithromycin (347,795
      prescriptions), propensity-score-matched persons who took no antibiotics
      (1,391,180 control periods), and patients who took amoxicillin (1,348,672
      prescriptions), ciprofloxacin (264,626 prescriptions), or levofloxacin (193,906
      prescriptions). RESULTS: During 5 days of therapy, patients taking azithromycin,
      as compared with those who took no antibiotics, had an increased risk of
      cardiovascular death (hazard ratio, 2.88; 95% confidence interval [CI], 1.79 to
      4.63; P<0.001) and death from any cause (hazard ratio, 1.85; 95% CI, 1.25 to
      2.75; P=0.002). Patients who took amoxicillin had no increase in the risk of
      death during this period. Relative to amoxicillin, azithromycin was associated
      with an increased risk of cardiovascular death (hazard ratio, 2.49; 95% CI, 1.38
      to 4.50; P=0.002) and death from any cause (hazard ratio, 2.02; 95% CI, 1.24 to
      3.30; P=0.005), with an estimated 47 additional cardiovascular deaths per 1
      million courses; patients in the highest decile of risk for cardiovascular
      disease had an estimated 245 additional cardiovascular deaths per 1 million
      courses. The risk of cardiovascular death was significantly greater with
      azithromycin than with ciprofloxacin but did not differ significantly from that
      with levofloxacin. CONCLUSIONS: During 5 days of azithromycin therapy, there was
      a small absolute increase in cardiovascular deaths, which was most pronounced
      among patients with a high baseline risk of cardiovascular disease. (Funded by
      the National Heart, Lung, and Blood Institute and the Agency for Healthcare
      Quality and Research Centers for Education and Research on Therapeutics.).

PMID- 22591295
TI  - Association of coffee drinking with total and cause-specific mortality.
AB  - BACKGROUND: Coffee is one of the most widely consumed beverages, but the
      association between coffee consumption and the risk of death remains unclear.
      METHODS: We examined the association of coffee drinking with subsequent total and
      cause-specific mortality among 229,119 men and 173,141 women in the National
      Institutes of Health-AARP Diet and Health Study who were 50 to 71 years of age at
      baseline. Participants with cancer, heart disease, and stroke were excluded.
      Coffee consumption was assessed once at baseline. RESULTS: During 5,148,760
      person-years of follow-up between 1995 and 2008, a total of 33,731 men and 18,784
      women died. In age-adjusted models, the risk of death was increased among coffee
      drinkers. However, coffee drinkers were also more likely to smoke, and, after
      adjustment for tobacco-smoking status and other potential confounders, there was
      a significant inverse association between coffee consumption and mortality.
      Adjusted hazard ratios for death among men who drank coffee as compared with
      those who did not were as follows: 0.99 (95% confidence interval [CI], 0.95 to
      1.04) for drinking less than 1 cup per day, 0.94 (95% CI, 0.90 to 0.99) for 1
      cup, 0.90 (95% CI, 0.86 to 0.93) for 2 or 3 cups, 0.88 (95% CI, 0.84 to 0.93) for
      4 or 5 cups, and 0.90 (95% CI, 0.85 to 0.96) for 6 or more cups of coffee per day
      (P<0.001 for trend); the respective hazard ratios among women were 1.01 (95% CI,
      0.96 to 1.07), 0.95 (95% CI, 0.90 to 1.01), 0.87 (95% CI, 0.83 to 0.92), 0.84
      (95% CI, 0.79 to 0.90), and 0.85 (95% CI, 0.78 to 0.93) (P<0.001 for trend).
      Inverse associations were observed for deaths due to heart disease, respiratory
      disease, stroke, injuries and accidents, diabetes, and infections, but not for
      deaths due to cancer. Results were similar in subgroups, including persons who
      had never smoked and persons who reported very good to excellent health at
      baseline. CONCLUSIONS: In this large prospective study, coffee consumption was
      inversely associated with total and cause-specific mortality. Whether this was a
      causal or associational finding cannot be determined from our data. (Funded by
      the Intramural Research Program of the National Institutes of Health, National
      Cancer Institute, Division of Cancer Epidemiology and Genetics.).

PMID- 22591297
TI  - Clinical practice. Secondary prevention after ischemic stroke or transient
      ischemic attack.

PMID- 22591296
TI  - Somatic STAT3 mutations in large granular lymphocytic leukemia.
AB  - BACKGROUND: T-cell large granular lymphocytic leukemia is a rare
      lymphoproliferative disorder characterized by the expansion of clonal CD3+CD8+
      cytotoxic T lymphocytes (CTLs) and often associated with autoimmune disorders and
      immune-mediated cytopenias. METHODS: We used next-generation exome sequencing to
      identify somatic mutations in CTLs from an index patient with large granular
      lymphocytic leukemia. Targeted resequencing was performed in a well-characterized
      cohort of 76 patients with this disorder, characterized by clonal T-cell-receptor
      rearrangements and increased numbers of large granular lymphocytes. RESULTS:
      Mutations in the signal transducer and activator of transcription 3 gene (STAT3)
      were found in 31 of 77 patients (40%) with large granular lymphocytic leukemia.
      Among these 31 patients, recurrent mutational hot spots included Y640F in 13
      (17%), D661V in 7 (9%), D661Y in 7 (9%), and N647I in 3 (4%). All mutations were
      located in exon 21, encoding the Src homology 2 (SH2) domain, which mediates the
      dimerization and activation of STAT protein. The amino acid changes resulted in a
      more hydrophobic protein surface and were associated with phosphorylation of
      STAT3 and its localization in the nucleus. In vitro functional studies showed
      that the Y640F and D661V mutations increased the transcriptional activity of
      STAT3. In the affected patients, downstream target genes of the STAT3 pathway
      (IFNGR2, BCL2L1, and JAK2) were up-regulated. Patients with STAT3 mutations
      presented more often with neutropenia and rheumatoid arthritis than did patients
      without these mutations. CONCLUSIONS: The SH2 dimerization and activation domain
      of STAT3 is frequently mutated in patients with large granular lymphocytic
      leukemia; these findings suggest that aberrant STAT3 signaling underlies the
      pathogenesis of this disease. (Funded by the Academy of Finland and others.).

PMID- 22591298
TI  - Images in clinical medicine. Nevus sebaceous.

PMID- 22591299
TI  - Case records of the Massachusetts General Hospital. Case 15-2012. A 48-year-old
      woman with diplopia, headaches, and papilledema.

PMID- 22591300
TI  - Predicting risk of progressive multifocal leukoencephalopathy from natalizumab.

PMID- 22591301
TI  - Stem cells and spinal cord repair.

PMID- 22591303
TI  - Intramuscular versus intravenous benzodiazepines for status epilepticus.

PMID- 22591304
TI  - Intramuscular versus intravenous benzodiazepines for status epilepticus.

PMID- 22591306
TI  - Memory enhancement and deep-brain stimulation of the entorhinal area.

PMID- 22591307
TI  - Memory enhancement and deep-brain stimulation of the entorhinal area.

PMID- 22591308
TI  - Memory enhancement and deep-brain stimulation of the entorhinal area.

PMID- 22591309
TI  - Images in clinical medicine. "Half-half" blisters.

PMID- 22591310
TI  - Effect of pH on the photophysical and redox properties of a ruthenium(II) mixed
      chelate derived from imidazole-4,5-dicarboxylic acid and 2,2'-bipyridine: an
      experimental and theoretical investigation.
AB  - Combined experimental and DFT-TD-DFT computational studies were utilized to
      investigate the structural and electronic properties of mixed-ligand monometallic
      ruthenium(II) complexes of compositions [(bpy)(2)Ru(H(2)Imdc)](+) (1(+)), its N-H
      deprotonated form [(bpy)(2)Ru(HImdc)] (1), and COOH deprotonated form
      [(bpy)(2)Ru(Imdc)](-) (1(-)), where H(3)Imdc = imidazole-4,5-dicarboxylic acid
      and bpy = 2,2'-bipyridine. The optimized geometrical parameters for the complexes
      computed both in the gas phase and in solution are reported and compared with the
      previously reported X-ray data. The influence of pH on the absorption, emission,
      and redox properties of [(bpy)(2)Ru(H(2)Imdc)](+) (1(+)) has been thoroughly
      investigated. The absorption titration data were used to determine the ground
      state pK values, whereas the luminescence data were utilized for the
      determination of excited state acid dissociation constants. The proton-coupled
      redox activity of 1(+) has been studied over the pH range 2-12 in acetonitrile
      water (3:2). From the E(1/2) versus pH profile, the equilibrium constants of the
      variously deprotonated complex species in Ru(II) and Ru(III) oxidation states
      have been determined. As compared to the protonated complex (1(+)), which
      undergoes reversible oxidation at 0.96 V (vs Ag/AgCl) in acetonitrile, the redox
      potential of the fully deprotonated complex (1(-)) is shifted to a much lower
      value, viz., 0.52 V. Density functional theory (DFT) and time-dependent DFT (TD
      DFT) study provides insight into the nature of the ground and excited states with
      resulting detailed assignments of the orbitals involved in absorption and
      emission transitions. In particular, the red-shifts of the absorption and
      emission bands and the cathodic shift in the oxidation potential of 1(+) compared
      to 1 and 1(-) are also reproduced by our calculations.

PMID- 22591311
TI  - Persistent and diffuse hair graying after recovery from alopecia totalis.

PMID- 22591313
TI  - Abstracts of the First International Science Symposium on HIV and Infectious
      Diseases (HIV SCIENCE 2012), 20-22 January, 2012, Chennai, India.

PMID- 22591312
TI  - Fish scale collagen--a novel material for corneal tissue engineering.
AB  - The ex vivo cultured limbal stem cells over a biocompatible scaffold are used in
      the management of limbal stem cell deficiency as an ideal replacement for human
      amniotic membrane (HAM). A novel source of collagen from fish scales (FSC) was
      used to fabricate the scaffold. In this study, we have evaluated the
      physicochemical, mechanical, and culture characteristics of FSC and compared with
      denuded HAM. The cultured corneal cells were characterized by real-time
      polymerase chain reaction for putative stem cell markers. The swelling ratio,
      collagenase assay, and microbial resistance of FSC gave better results when
      compared to those of HAM. The mechanical and physical strengths of FSC were good
      enough to handle when compared to HAM. Under microscopic observation, epithelial
      migration was noted at the end of 48 h from limbal explants plated on FSC and on
      HAM at the end of 72 h. By the end of the 15th day, 90 to 100% confluent growth
      was seen resembling the morphological features of limbal epithelium. In
      conclusion, FSCs from a novel renewable biological source were optically clear
      with sufficient strength, and gave encouraging results in culture studies; the
      same may be tried as potential candidate for corneal transplantation after in
      vivo studies.

PMID- 22591314
TI  - Accumulation of phosphate and polyphosphate by  Cryptococcus humicola and 
      Saccharomyces cerevisiae in the absence of nitrogen.
AB  - The search for new phosphate-accumulating microorganisms is of interest in
      connection with the problem of excess phosphate in environment. The ability of
      some yeast species belonging to ascomycetes and basidiomycetes for phosphate (P
      (i) ) accumulation in nitrogen-deficient medium was studied. The ascomycetous
      Saccharomyces cerevisiae and Kuraishia capsulata and basidiomycetous Cryptococcus
      humicola, Cryptococcus curvatus, and Pseudozyma fusiformata were the best in P
      (i)  removal. The cells of Cryptococcus humicola and S. cerevisiae took up 40% P
      (i)  from the media containing P (i)  and glucose (5 and 30 mM, respectively),
      and up to 80% upon addition of 5 mM MgSO(4) (.)  The cells accumulated P (i) 
      mostly in the form of polyphosphate (PolyP). In the presence of Mg(2+)  , the
      content of PolyP with longer average chain length increased in both yeasts; they
      both had numerous inclusions fluorescing in the yellow region of the spectrum,
      typical of DAPI-PolyP complexes. Among the yeast species tested, Cryptococcus
      humicola is a new promising model organisms to study phosphorus removal from the
      media and biomineralization in microbial cells.

PMID- 22591316
TI  - The effect of angiotensin-converting enzyme inhibition by captopril on
      respiratory mechanics in healthy rats.
AB  - CONTEXT: Angiotensin stimulates smooth-muscle contraction. Accordingly,
      angiotensin-converting enzyme (ACE) inhibition is expected to decrease airway
      resistance. OBJECTIVES: To measure the effects of ACE inhibition on respiratory
      mechanics in healthy mammals. MATERIALS AND METHODS: We measured respiratory
      mechanics before and after i.p. ACE inhibitor captopril (100 mg/kg) in normal
      anaesthetised rats. The end-inflation occlusion method allowed the measurements
      of respiratory system elastance and ohmic and viscoelastic pressure dissipations.
      Respiratory system hysteresis and the elastic and resistive work of breathing
      were calculated. RESULTS: Captopril induced a reduction of the ohmic and the
      total respiratory system resistances, while respiratory system hysteresis and
      elastance did not change. Accordingly, a reduction of the resistive and of the
      total work of breathing was observed. CONCLUSIONS: The captopril-induced
      reduction of airway resistance indicates that angiotensin modulates bronchomotor
      tone in basal conditions. ACE inhibition may positively affect respiratory system
      mechanics and work of breathing.

PMID- 22591315
TI  - Single-molecule spectroscopic study of dynamic nanoscale DNA bending behavior of
      HIV-1 nucleocapsid protein.
AB  - We have studied the conformational dynamics associated with the nanoscale DNA
      bending induced by human immunodeficiency virus type 1 (HIV-1) nucleocapsid (NC)
      protein using single-molecule Forster resonance energy transfer (SM-FRET). To
      gain molecular-level insights into how the HIV-1 NC locally distorts the
      structures of duplexed DNA segments, the dynamics, reversibility, and sequence
      specificity of the DNA bending behavior of NC have been systematically studied.
      We have performed SM-FRET measurements on a series of duplexed DNA segments with
      varying sequences, lengths, and local structures in the presence of the wide-type
      HIV-1 NC and NC mutants lacking either the basic N-terminal domain or the zinc
      fingers. On the basis of the SM-FRET results, we have proposed a possible
      mechanism for the NC-induced DNA bending in which both NC's zinc fingers and N
      terminal domain are found to play crucial roles. The SM-FRET results reported
      here add new mechanistic insights into the biological behaviors and functions of
      HIV-1 NC as a retroviral DNA-architectural protein which may play critical roles
      in the compaction, nuclear import, and integration of the proviral DNA during the
      retroviral life cycle.

PMID- 22591317
TI  - Impacts of some antibiotics on human serum paraoxonase 1 activity.
AB  - Some enzymes are known to be drug target inhibitions of which can be critical for
      organisms. PON has a critical role to prevent atherogenesis by inhibiting lipid
      peroxidation. It is well known that paraoxonase 1 (PON1) plays an important
      function on high-density lipoprotein (HDL) structure to prevent lipid oxidation
      not only of low-density lipoprotein, but also of HDL itself. We investigated in
      vitro effects of some medical drugs on PON1 activity from human serum. Ki
      constants for oxytetracycline hydrochloride, netilmycin sulfate, lincomycin
      hydrochloride, clindamycin phosphate, and streptomycin sulfate were found as 0.2,
      3.73, 18.30, 35.80, and 56.30 mM, respectively. Our results indicate that these
      commonly used drugs inhibit the activity of the enzyme at very low doses with
      different inhibition mechanisms. 

PMID- 22591318
TI  - Synthesis of purine homo-N-nucleosides modified with coumarins as free radicals
      scavengers.
AB  - Cross metathesis (CM) of 9-butenylpurines with 4-butenyloxycoumarin in the
      presence of Grubbs 2nd generation catalyst under MW irradiation resulted to
      conjugated compounds containing homo-N-nucleosides and coumarins. Analogous
      derivatives received by the CM reaction of 9-butenyl-6-piperidinylpurine with 6-
      or 7-butenyloxycoumarins, allyloxycoumarins or coumarinyl acrylate. These
      compounds were tested in vitro for their antioxidant activity and they present
      significant scavenging activity. The presence of a pentenyloxy moiety, the
      attachment position on coumarin ring as well as a purine homo-N-nucleoside group
      are considered as important structural features. 

PMID- 22591319
TI  - Conformation depends on 4D-QSAR analysis using EC-GA method: pharmacophore
      identification and bioactivity prediction of TIBOs as non-nucleoside reverse
      transcriptase inhibitors.
AB  - The electron conformational and genetic algorithm methods (EC-GA) were integrated
      for the identification of the pharmacophore group and predicting the anti HIV-1
      activity of tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepinone (TIBO) derivatives.
      To reveal the pharmacophore group, each conformation of all compounds was
      arranged by electron conformational matrices of congruity. Multiple comparisons
      of these matrices, within given tolerances for high active and low active TIBO
      derivatives, allow the identification of the pharmacophore group that refers to
      the electron conformational submatrix of activity. The effects of conformations,
      internal and external validation were investigated by four different models based
      on an ensemble of conformers and a single conformer, both with and without a test
      set. Model 1 using an ensemble of conformers for the training (39 compounds) and
      test sets (13 compounds), obtained by the optimum seven parameters, gave
      satisfactory results (R2(training) = 0.878, R2(test)= 0.910, q2 = 0.840, q2(ext1)
      = 0.926 and q2(ext2) = 0.900).

PMID- 22591320
TI  - The protective effect of docosahexaenoic acid on the bilirubin neurotoxicity.
AB  - Usually, all newborns demonstrate high serum unconjugated bilirubin (UCB) level.
      UCB may induce adverse effects in the central nervous system. We aimed to
      evaluate the cytotoxic effects of UCB and the protective effects of
      docosahexaenoic acid (DHA) on astrocyte cell cultures. The viability of astrocyte
      cells decreased after UCB treatment in a dose-dependent manner. Pre-incubation of
      DHA prevents the cells from UCB-mediated neurotoxicity. Our results shown that
      UCB leads to inhibition of antioxidant enzymes superoxide dismutase (SOD),
      catalase and GPx activity and induction of apoptosis. But only 4-h pretreatment
      of DHA can suppress of UCB-mediated inhibition of antioxidant enzymes SOD,
      catalase and GPx activity and induction of apoptosis in astrocytes. Our results
      strongly indicated that DHA has a protective effect on UCB-mediated neurotoxicity
      through inhibition apoptosis and antioxidant enzymes activity of SOD, CAT and GPx
      in rat primer astrocyte cell line. 

PMID- 22591321
TI  - Breaking camouflage: responses of neurons in the middle temporal area to stimuli
      defined by coherent motion.
AB  - Camouflaged animals remain inconspicuous only insofar as they remain static. This
      demonstrates that motion is a powerful cue for figure-ground segregation,
      allowing detection of moving objects even when their luminance and texture
      characteristics are matched to the background. We investigated the neural
      processes underlying this phenomenon by testing the responses of neurons in the
      middle temporal area (MT) to 'camouflaged' bars, which were rendered visible by
      motion. These responses were compared with those elicited by 'solid' bars, which
      also differed from background in terms of their mean luminance. Most MT neurons
      responded strongly to camouflaged bars, and signaled their direction of motion
      with precision, with direction-tuning curves being only slightly wider than those
      measured with solid bars. However, the tuning of most MT cells to stimulus length
      and speed depended on the type of stimulus - in comparison with solid bars,
      responses to camouflaged bars typically showed more extensive length summation,
      weak end-inhibition, and stronger attenuation at high speeds. Moreover, the
      emergence of direction selectivity was delayed in trials involving camouflaged
      bars, relative to solid bars. Comparison with results obtained in the first (V1)
      and second (V2) visual areas, using similar stimuli, indicates that neural
      computations performed in MT result in significantly stronger and more accurate
      signals about camouflaged objects, particularly in situations in which these are
      relatively large and slow moving. These computations are likely to represent an
      important step in enabling cue-invariant perception of moving objects,
      particularly in biologically relevant situations.

PMID- 22591322
TI  - Multifunctional hyperbranched glycoconjugated polymers based on natural
      aminoglycosides.
AB  - Multifunctional gene vectors with high transfection, low cytotoxicity, and good
      antitumor and antibacterial activities were prepared from natural
      aminoglycosides. Through the Michael-addition polymerization of gentamycin and
      N,N'-methylenebisacrylamide, cationic hyperbranched glycoconjugated polymers were
      synthesized, and their physical and chemical properties were analyzed by FTIR,
      (1)H NMR, (13)C NMR, GPC, zeta-potential, and acid-base titration techniques. The
      cytotoxicity of these hyperbranched glycoconjugated polycations was low because
      of the hydrolysis of degradable glycosidic and amide linkages in acid conditions.
      Owing to the presence of various primary, secondary, and tertiary amines in the
      polymers, hyperbranched glycoconjugated polymers showed high buffering capacity
      and strong DNA condensation ability, resulting in the high transfection
      efficiency. In the meantime, due to the introduction of natural aminoglycosides
      into the polymeric backbone, the resultant hyperbranched glycoconjugated polymers
      inhibited the growth of cancer cells and bacteria efficiently. Combining the gene
      transfection, antitumor, and antibacterial abilities together, the
      multifunctional hyperbranched glycoconjugated polymers based on natural
      aminoglycosides may play an important role in protecting cancer patients from
      bacterial infections. 

PMID- 22591323
TI  - Chiral nanocrystals: plasmonic spectra and circular dichroism.
AB  - The life is inherently chiral. Consequently, chirality plays a pivotal role in
      biochemistry and the evolution of life itself. Optical manifestation of chirality
      of biomolecules, so-called circular dichroism, is a remarkable but relatively
      weak effect appearing typically in the UV. In contrast to the biomolecules,
      plasmonic nanocrystals offer an interesting opportunity to create strong circular
      dichroism (CD) in the visible spectral range. Here we describe plasmonic
      properties of single chiral nanocrystals and focus on a new mechanism of optical
      chirality originating from a chiral shape of a nanocrystal. After careful
      examination, we found that this CD mechanism is induced by the mixing between
      different plasmon harmonics and is qualitatively different from the previously
      described dipolar CD effect in chiral assemblies of spherical nanoparticles.
      Chiral plasmonic nanocrystals studied here offer a new approach for the creation
      of nanomaterials with strong chiroptical responses in the visible spectral
      interval.

PMID- 22591325
TI  - Switching Kr/Xe selectivity with temperature in a metal-organic framework.
AB  - Krypton (Kr) and xenon (Xe) adsorption on two partially fluorinated metal-organic
      frameworks (FMOFCu and FMOFZn) with different cavity size and topologies are
      reported. FMOFCu shows an inversion in sorption selectivity toward Kr at
      temperatures below 0  degrees C while FMOFZn does not. The 1D microtubes packed
      along the (101) direction connected through small bottleneck windows in FMOFCu
      appear to be the reason for this peculiar behavior. The FMOFCu shows an estimated
      Kr/Xe selectivity of 36 at 0.1 bar and 203 K.

PMID- 22591324
TI  - Gas chromatographic-olfactometric aroma profile and quantitative analysis of
      volatile carbonyls of grilled beef from different finishing feed systems.
AB  - In this study, the important odor impact volatiles generated in the meat of
      grilled beef loin muscle were characterized. Animals were finished in 4 different
      diet systems: T1, pasture (a mixture of Medicago sativa, Trifolium repens, and
      Festuca arundinacea); T2, pasture supplemented with cracked corn grain (offered
      at 0.6% live weight, LW); T3, pasture supplemented with cracked corn grain
      (offered at 1.2% LW); and T4, concentrate (pellets with 85% corn and 12.8%
      sunflower, on a dry-matter basis) plus alfalfa hay (both ad libitum). Aroma
      compounds were assessed by dynamic headspace-solid phase extraction (DHS-SPE) and
      gas chromatographic-olfactometric (GC-O) analysis. Most odorants were carbonyl
      compounds, some of them reaching high GC-O scores, especially 1-octen-3-one, (E)
      2-octenal, methional, and hexanal. A specific quantitative analysis of ketones
      and aldehydes was conducted through their derivatization with o-(2,3,4,5,6
      pentafluorobenzyl) hydroxylamine hydrochloride directly on the headspace trap and
      analyzed by GC-MS, with the purpose of studying the effect of finishing diet
      systems. From the 23 carbonyl compounds quantified, 2 were especially affected by
      the diet system; methional was higher in the treatment based on concentrates,
      whereas (E,E)-2,4-heptadienal was higher in the treatment based only in pastures.
      The results are discussed considering previous published productive and quality
      traits. PRACTICAL APPLICATION: The knowledge of how production factors, such as
      animal feeding, can affect the flavor of meat is of significant interest toward
      in achieving a high-quality and differentiated product. The development of more
      specific and efficient methodologies is necessary to analyze meat aroma
      compounds, which would be used as routine analysis, that is for product
      authentication. In the future, the use of this analysis would allow producing and
      designing specific foods according to different markets.

PMID- 22591326
TI  - Grasping the dynamics of suicidal behaviour: combining time-geographic life
      charting and COPE ratings.
AB  - ACCESSIBLE SUMMARY: *  A primary aim of suicide research is to gain a profound
      knowledge of the suicidal individual so preventive strategy can be formulated. * 
      Time-geographic life charting used in combination with the pattern of coping
      strategies may be helpful when assessing risk of suicidal behaviour. *  It can
      also be a therapeutic intervention to look back and to reflect coping styles.
      ABSTRACT: The aim of this study is to explore whether a time-geographic life
      charting, combined with a survey of a person's coping capacities over time,
      elucidates the pathway to suicidal behaviour, and therefore could be useful in
      suicide prevention. Twenty-three patients were recruited shortly after a suicide
      attempt. A time-geographic life charting and COPE inventory ratings were used
      separately and in combination. According to COPE ratings, the participants could
      be divided into three groups using different coping strategies: (1) adaptive, (2)
      maladaptive, and (3) both adaptive and maladaptive coping. Within these
      subgroups, three different pathways to suicidal behaviour were described and
      illustrated. We conclude that time-geographic life charting used in combination
      with the pattern of coping strategies may be helpful when assessing risk of
      suicidal behaviour, because this approach strengthens the comprehensive picture
      of the patient's life situation.

PMID- 22591327
TI  - Identification and characterization of xiamycin A and oxiamycin gene cluster
      reveals an oxidative cyclization strategy tailoring indolosesquiterpene
      biosynthesis.
AB  - Xiamycin A (XMA) and oxiamycin (OXM) are bacterial indolosesquiterpenes featuring
      rare pentacyclic ring systems and are isolated from a marine-derived 
      Streptomyces  sp. SCSIO 02999. The putative biosynthetic gene cluster for XMA/OXM
      was identified by a partial genome sequencing approach. Eighteen genes were
      proposed to be involved in XMA/OXM biosynthesis, including five genes for terpene
      synthesis via a non-mevalonate pathway, eight genes encoding oxidoreductases, and
      five genes for regulation and resistance. Targeted disruptions of 13 genes within
      the xia gene cluster were carried out to probe their encoded functions in XMA/OXM
      biosynthesis. The disruption of xiaK, encoding an aromatic ring hydroxylase, led
      to a mutant producing indosespene and a minor amount of XMA. Feeding of
      indosespene to XMA/OXM nonproducing mutants revealed indosespene as a common
      precursor for XMA/OXM biosynthesis. Most notably, the flavin dependent oxygenase
      XiaI was biochemically characterized in vitro to convert indosespene to XMA,
      revealing an unusual oxidative cyclization strategy tailoring indolosesquiterpene
      biosynthesis.

PMID- 22591329
TI  - Plasma cell myeloma with intracytoplasmic crystalloid inclusions, mimicking a
      Niemann-Pick disease.

PMID- 22591328
TI  - Effects of SCN1A and GABA receptor genetic polymorphisms on carbamazepine
      tolerability and efficacy in Chinese patients with partial seizures: 2-year
      longitudinal clinical follow-up.
AB  - AIMS: To investigate the tolerability and efficacy of carbamazepine treatment in
      patients with partial-onset seizures and the association with polymorphisms in
      the sodium channel alpha-subunit type 1 (SCN1A), and gamma-aminobutyric acid
      (GABA) receptor genes among the Chinese Han population. METHODS: 448 patients
      were genotyped for single nucleotide polymorphisms selected of the SCN1A and GABA
      receptor genes. Monotherapy with carbamazepine (CBZ) was administered to the
      patients. The effectiveness of CBZ treatment was evaluated with regard to
      efficacy by the decrease in seizures and tolerability by retention rates.
      RESULTS: SCN1A rs3812718 A/G with CBZ tolerability (P= 0.038) throughout 24
      months of clinical follow-up and the GABRA1 rs2290732 A/G were significantly
      associated with CBZ tolerability (P= 0.001). The maintenance dose and serum level
      of CBZ in AA genotype carriers of rs3812718 A/G were significantly higher than
      those of GG genotype carriers between 3 and 12 months of follow-up. The
      proportion of AA genotype carriers of rs2298771 A/G with seizure free was
      significantly higher than that of AG+GG genotype carriers from 3 months to 15
      months of follow-up (P < 0.05). CONCLUSION: rs3812718 A/G and rs2290732 A/G
      polymorphisms affected the tolerability of CBZ. rs2298771 A/G was associated with
      efficacy of CBZ treatment.

PMID- 22591330
TI  - Cigarette smoke augments the expression and responses of toll-like receptor 3 in
      human macrophages.
AB  - BACKGROUND AND OBJECTIVE: Cigarette smoking is the main risk factor for the
      development of chronic obstructive pulmonary disease (COPD). Recently, toll-like
      receptor 3 (TLR3) was shown to recognize pathogen-associated molecular patterns,
      especially viral-derived double-stranded RNA, and to be involved in immune
      responses. However, the effects of cigarette smoke on TLR3 remain unclear. In
      this study, it was examined whether cigarette smoke affects the expression and
      responses of TLR3 in human macrophages. METHODS: The expression of TLR3 in
      alveolar macrophages from human lung tissues was analysed by
      immunohistochemistry, and the correlation of TLR3 expression with smoking history
      and lung function was evaluated. In addition, the effect of cigarette smoke on
      the expression and responses of TLR3 in macrophage lineage cells was
      investigated. RESULTS: TLR3-positive alveolar macrophage numbers were
      significantly increased in smokers and COPD patients compared with non-smoking
      control subjects, but there was no difference between smokers and COPD patients.
      TLR3-positive macrophage numbers were positively correlated with smoking history
      and inversely correlated with corrected carbon monoxide diffusing capacity, but
      were not correlated with % predicted forced expiratory volume in 1 s.
      Furthermore, cigarette smoke extract potentiated the expression of TLR3 in
      monocyte-derived macrophages and significantly augmented the release of
      interleukin-8, as well as total matrix metalloproteinase-9 activity, in cells
      treated with TLR3 ligand. CONCLUSIONS: These data suggest that cigarette smoke
      augments the expression and responses of TLR3 in human macrophages, and this may
      contribute to neutrophilic airway inflammation and parenchymal destruction in the
      lungs of smokers and patients with COPD.

PMID- 22591331
TI  - Direct synthesis of cup-stacked carbon nanofiber microspheres by the catalytic
      pyrolysis of poly(ethylene glycol).
AB  - Uniformly sized microspheres tangled with cup-stacked carbon nanofibers (CSCNFs)
      were directly synthesized by the pyrolysis of poly(ethylene glycol) (PEG) with a
      nickel catalyst. A PEG/Ni membrane was prepared on a silicon wafer surface by
      heating it to 750  degrees C at a heating rate of 15  degrees C min(-1). The
      wafer was heated to a temperature of 400  degrees C and was held at that
      temperature for 1 h before raising the temperature to 750  degrees C for 10 min
      to form the CSCNF microspheres. The final CSCNF microspheres and the
      intermediates were evaluated using scanning electron microscopy, transmission
      electron microscopy, X-ray diffractometry, and Raman spectroscopy to elucidate
      the growth mechanism. Furthermore, the CSCNF microspheres were successfully
      dispersed and maintained their spherical shape in an aqueous solution containing
      0.5% Nafion. The CSCNF microspheres have the potential to work as a sophisticated
      carrier with high adsorption and fast electron-transfer exchange properties based
      on the graphene edges of the nanofiber surface.

PMID- 22591332
TI  - The effects of rehabilitative training on the behaviors of Parkinson's disease
      mouse and underlying mechanism.
AB  - OBJECTIVE: To examine the effects of rehabilitative training on mice behavior
      improvement in a 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) mice model
      of Parkinson's disease (PD). METHODS: MPTP mice model of Parkinson disease was
      generated. The rehabilitative training included daily running wheel and balance
      walking; the control group was allowed for free activity. The behaviors of the
      two groups were investigated at 1 week, 2 weeks, and 4 weeks and the content of
      dopamine (DA) in striatum of different groups of mice was measured with high
      performance liquid chromatography (HPLC). RESULTS: The results showed that as
      compared to the control group, the score of climbing pole, traction, swimming
      tests, and dopamine content was improved in the rehabilitative training group.
      CONCLUSION: This suggested that rehabilitative training could improve the
      locomotor ability and dopamine content in PD mouse model.

PMID- 22591333
TI  - Global warming reduces plant reproductive output for temperate multi
      inflorescence species on the Tibetan plateau.
AB  - * Temperature is projected to increase more during the winter than during the
      summer in cold regions. The effects of winter warming on reproductive effort have
      not been examined for temperate plant species. * Here, we report the results of
      experimentally induced seasonal winter warming (0.4 and 2.4 degrees C increases
      in growing and nongrowing seasons, respectively, using warmed and ambient open
      top chambers in a Tibetan Plateau alpine meadow) for nine indeterminate-growing
      species producing multiple (single-flowered or multi-flowered) inflorescences and
      three determinate-growing species producing single inflorescences after a 3-yr
      period of warming. * Warming reduced significantly flower number and seed
      production per plant for all nine multi-inflorescence species, but not for the
      three single-inflorescence species. Warming had an insignificant effect on the
      fruit to flower number ratio, seed size and seed number per fruit among species.
      The reduction in seed production was largely attributable to the decline in
      flower number per plant. The flowering onset time was unaffected for nine of the
      12 species. Therefore, the decline in flower production and seed production in
      response to winter warming probably reflects a physiological response (e.g.
      metabolic changes associated with flower production). * Collectively, the data
      indicate that global warming may reduce flower and seed production for temperate
      herbaceous species and will probably have a differential effect on single- vs
      multi-inflorescence species.

PMID- 22591334
TI  - MHC genotype predicts mate choice in the ring-necked pheasant Phasianus
      colchicus.
AB  - Females of several vertebrate species selectively mate with males on the basis of
      the major histocompatibility complex (MHC) genes. As androgen-mediated maternal
      effects have long-lasting consequences for the adult phenotype, both mating and
      reproductive success may depend on the combined effect of MHC genotype and
      exposure to androgens during early ontogeny. We studied how MHC-based mate choice
      in ring-necked pheasants (Phasianus colchicus) was influenced by an experimental
      in ovo testosterone (T) increase. There was no conclusive evidence of in ovo T
      treatment differentially affecting mate choice in relation to MHC genotype.
      However, females avoided mating with males with a wholly different MHC genotype
      compared with males sharing at least one MHC allele. Females also tended to avoid
      mating with MHC-identical males, though not significantly so. These findings
      suggest that female pheasants preferred males with intermediate MHC
      dissimilarity. Male MHC heterozygosity or diversity did not predict the
      expression of ornaments or male dominance rank. Thus, MHC-based mating
      preferences in the ring-necked pheasant do not seem to be mediated by ornaments'
      expression and may have evolved mainly to reduce the costs of high heterozygosity
      at MHC loci for the progeny, such as increased risk of autoimmune diseases or
      disruption of coadapted gene pools.

PMID- 22591335
TI  - Segmentation of corpus callosum using diffusion tensor imaging: validation in
      patients with glioblastoma.
AB  - BACKGROUND: This paper presents a three-dimensional (3D) method for segmenting
      corpus callosum in normal subjects and brain cancer patients with glioblastoma.
      METHODS: Nineteen patients with histologically confirmed treatment naive
      glioblastoma and eleven normal control subjects underwent DTI on a 3T scanner.
      Based on the information inherent in diffusion tensors, a similarity measure was
      proposed and used in the proposed algorithm. In this algorithm, diffusion pattern
      of corpus callosum was used as prior information. Subsequently, corpus callosum
      was automatically divided into Witelson subdivisions. We simulated the potential
      rotation of corpus callosum under tumor pressure and studied the reproducibility
      of the proposed segmentation method in such cases. RESULTS: Dice coefficients,
      estimated to compare automatic and manual segmentation results for Witelson
      subdivisions, ranged from 94% to 98% for control subjects and from 81% to 95% for
      tumor patients, illustrating closeness of automatic and manual segmentations.
      Studying the effect of corpus callosum rotation by different Euler angles showed
      that although segmentation results were more sensitive to azimuth and elevation
      than skew, rotations caused by brain tumors do not have major effects on the
      segmentation results. CONCLUSIONS: The proposed method and similarity measure
      segment corpus callosum by propagating a hyper-surface inside the structure
      (resulting in high sensitivity), without penetrating into neighboring fiber
      bundles (resulting in high specificity).

PMID- 22591336
TI  - Cushing's syndrome induced by high-potency topical corticosteroids.

PMID- 22591337
TI  - Transcriptional regulation of fermentative and respiratory metabolism in 
      Saccharomyces cerevisiae industrial bakers' strains.
AB  - Bakers' yeast-producing companies grow cells under respiratory conditions, at a
      very high growth rate. Some desirable properties of bakers' yeast may be altered
      if fermentation rather than respiration occurs during biomass production. That is
      why differences in gene expression patterns that take place when industrial
      bakers' yeasts are grown under fermentative, rather than respiratory conditions,
      were examined. Macroarray analysis of V1 strain indicated changes in gene
      expression similar to those already described in laboratory Saccharomyces
      cerevisiae strains: repression of most genes related to respiration and oxidative
      metabolism and derepression of genes related to ribosome biogenesis and stress
      resistance in fermentation. Under respiratory conditions, genes related to the
      glyoxylate and Krebs cycles, respiration, gluconeogenesis, and energy production
      are activated. DOG21 strain, a partly catabolite-derepressed mutant derived from
      V1, displayed gene expression patterns quite similar to those of V1, although
      lower levels of gene expression and changes in fewer number of genes as compared
      to V1 were both detected in all cases. However, under fermentative conditions,
      DOG21 mutant significantly increased the expression of SNF1 -controlled genes and
      other genes involved in stress resistance, whereas the expression of the HXK2
      gene, involved in catabolite repression, was considerably reduced, according to
      the pleiotropic stress-resistant phenotype of this mutant. These results also
      seemed to suggest that stress-resistant genes control desirable bakers' yeast
      qualities.

PMID- 22591338
TI  - Tissue-selective regulation of androgen-responsive genes.
AB  - INTRODUCTION: Androgens regulate a wide array of physiological processes,
      including male sexual development, bone and muscle growth, and behavior and
      cognition. Because androgens play a vital role in so many tissues, changes in
      androgen signaling are associated with a plethora of diseases. How such varied
      responses are achieved by a single stimulus is not well understood. Androgens act
      primarily through the androgen receptor (AR), a hormone nuclear receptor that is
      expressed in a select variety of tissues. METHODS: In order to gain a better
      understanding of how the tissue-selective effects of androgens are achieved, we
      performed a comparison of microarray data, using previously published datasets
      and several of our own microarray datasets. These datasets were derived from
      clinically relevant, AR-expressing tissues dissected from rodents treated with
      the full androgen dihydrotestosterone (DHT). RESULTS: We found that there is a
      diverse response to DHT, with very little overlap of androgen regulated genes in
      each tissue. Gene ontology analyses also indicated that, while several tissues
      regulate similar biological processes in response to DHT, most androgen regulated
      processes are specific to one or a few tissues. Thus, it appears that the
      disparate physiological effects mediated by androgens begin with widely varying
      effects on gene expression in different androgen-sensitive tissues. CONCLUSION:
      The analysis completed in this study will lead to an improved understanding of
      how androgens mediate diverse, tissue-specific processes and better ways to
      assess the tissue-selective effects of AR modulators during drug development.

PMID- 22591339
TI  - Oxidative stability of virgin olive oil as affected by the bene unsaponifiable
      matters and tertiary-butylhydroquinone.
AB  - During 16 h heating at 180  degrees C, the oxidative stability (OS) of virgin
      olive oil (VOO) as affected by the same concentrations (200 ppm) of tertiary
      butylhydroquinone (TBHQ) and unsaponifiable matters of bene kernel (UKO) and hull
      (UHO) oils in terms of the inhibitory effect on the formation of conjugated diene
      hydroperoxides (OS(CDV)) and off-flavor carbonyl compounds (OS(CV)) was
      investigated. TBHQ was not able to considerably increase the OS(CDV) (7.51) of
      the VOO (7.2) and showed no synergistic effect with indigenous antioxidative
      compounds of the VOO (IOV) in this respect. However, it could significantly
      improve the OS(CV) (from 2.49 to 4.52), which was mainly due to its synergism
      with the IOV. The UKO increased considerably the OS(CDV) (to 11.8), and its
      OS(CV) (4.22) was nearly the same as that of TBHQ. The IOV still had marked
      contributions to the prevention of VOO oxidation but the majority of stabilizing
      effect was related to the UKO and its synergism with the IOV. The OS(CDV) in
      presence of the UHO was less than that of the VOO (5.96), although it
      significantly increased the OS(CV) (to 5.2), mainly due to the stabilizing effect
      of UHO and its synergism with the IOV.

PMID- 22591340
TI  - An impression on current developments in the technology, chemistry, and
      biological activities of ginger (Zingiber officinale Roscoe).
AB  - Ginger rhizome (Zingiber officinale Roscoe) is widely cultivated as a spice for
      its aromatic and pungent components. The essential oil and oleoresins from ginger
      are valuable products responsible for the characteristic flavor and pungency.
      Both are used in several food products such as soft beverages and also in many
      types of pharmaceutical formulations. More than 100 compounds have been reported
      from ginger, some of which are isolated and characterized, others are tentatively
      identified by GC-MS and / or LC-MS. [6]-Gingerol, the major gingerol in ginger
      rhizomes, has been found to possess many interesting pharmacological and
      physiological activities, such as anti-inflammatory, analgesic, and cardiotonic
      effects. Ginger is considered as "generally recognized as safe" (GRAS) by Food
      and Drug Administration (FDA), USA. Due to all these properties, ginger has
      gained considerable attention in developed countries in recent years, especially
      for its use in the treatment of inflammatory conditions. The present review is a
      persuasive presentation of the current information on processing, chemistry,
      biological activities, and medicinal uses of ginger. Further studies are required
      for the validation of the beneficial uses. Formulation for novel products and new
      usages may emerge in the years to come, based on the revealed results of various
      studies.

PMID- 22591341
TI  - Meat quality evaluation by hyperspectral imaging technique: an overview.
AB  - During the last two decades, a number of methods have been developed to
      objectively measure meat quality attributes. Hyperspectral imaging technique as
      one of these methods has been regarded as a smart and promising analytical tool
      for analyses conducted in research and industries. Recently there has been a
      renewed interest in using hyperspectral imaging in quality evaluation of
      different food products. The main inducement for developing the hyperspectral
      imaging system is to integrate both spectroscopy and imaging techniques in one
      system to make direct identification of different components and their spatial
      distribution in the tested product. By combining spatial and spectral details
      together, hyperspectral imaging has proved to be a promising technology for
      objective meat quality evaluation. The literature presented in this paper clearly
      reveals that hyperspectral imaging approaches have a huge potential for gaining
      rapid information about the chemical structure and related physical properties of
      all types of meat. In addition to its ability for effectively quantifying and
      characterizing quality attributes of some important visual features of meat such
      as color, quality grade, marbling, maturity, and texture, it is able to measure
      multiple chemical constituents simultaneously without monotonous sample
      preparation. Although this technology has not yet been sufficiently exploited in
      meat process and quality assessment, its potential is promising. Developing a
      quality evaluation system based on hyperspectral imaging technology to assess the
      meat quality parameters and to ensure its authentication would bring economical
      benefits to the meat industry by increasing consumer confidence in the quality of
      the meat products. This paper provides a detailed overview of the recently
      developed approaches and latest research efforts exerted in hyperspectral imaging
      technology developed for evaluating the quality of different meat products and
      the possibility of its widespread deployment.

PMID- 22591343
TI  - Distinctive exotic flavor and aroma compounds of some exotic tropical fruits and
      berries: a review.
AB  - The characteristic flavor of exotic tropical fruits is one of their most
      attractive attributes to consumers. In this article, the enormous diversity of
      exotic fruit flavors is reviewed. Classifying some of the exotic fruits into two
      classes on the basis of whether esters or terpenes predominate in the aroma was
      also attempted. Indeed, as far as exotic tropical fruits are concerned, the
      majority of fruits have terpenes predominating in their aroma profile. Some of
      the fruits in this group are the Amazonian fruits such as pitanga, umbu-caja,
      camu-camu, garcinia, and bacuri. The ester group is made up of rambutan, durians,
      star fruit, snake fruit, acerola, tamarind, sapodilla, genipap, soursop, cashew,
      melon, jackfruit, and cupuacu respectively. Also, the role of sulphur-volatiles
      in some of the exotic fruits is detailed.

PMID- 22591342
TI  - A review of the ecology, genomics, and stress response of Listeria innocua and
      Listeria monocytogenes.
AB  - Listeria monocytogenes is a Gram-positive foodborne pathogen responsible for a
      severe disease occurring in immuno-compromised populations. Foodborne illness
      caused by L. monocytogenes is a serious public health concern because of the high
      associated mortality. Study of the closely related, but nonpathogenic Listeria
      innocua has accounted for a better understanding of the behavior of L.
      monocytogenes in environments beyond the laboratory. Traditionally, the
      ecological co-habitation, genomic synteny, and physiological similarity of the
      two species have supported use of L. innocua for predicting the behavior of L.
      monocytogenes in farm and food processing environments. However, a careful review
      of the current literature indicates that in a given situation it may not be
      prudent to use L. innocua as a surrogate for L. monocytogenes without prior
      confirmation of their similar phenotypes, as an increasing number of studies have
      arisen demonstrating differences in L. monocytogenes and L. innocua stress
      response, and furthermore, there are differences among the L. monocytogenes
      subgroups. Future research should take into consideration that multiple
      surrogates might be required to accurately model even a single condition
      depending on the L. monocytogenes subgroup of interest.

PMID- 22591344
TI  - Functional genomics- and network-driven systems biology approaches for
      pharmacogenomics and toxicogenomics.
AB  - Recent advances in genomic technologies have enabled the identification of
      thousands of genetic variations that are associated with hundreds of complex
      human diseases or traits in genome-wide association studies (GWAS). The large
      number of genetic loci uncovered for each disease or trait along with the
      difficulty in pinpointing the underlying genes and mechanisms further testify to
      the complexity of human pathophysiology. To alleviate the challenges of GWAS,
      systems biology approaches have been utilized to map the molecular mechanisms
      underlying complex human diseases/traits via the integration of genetic
      variation, functional genomics (such as genetics of gene expression), pathways,
      and molecular networks. Similar approaches have been applied to a spectrum of
      drug metabolizing enzymes to discover novel functional genetic variations that
      affect the expression or activities of these enzymes as well as to define the
      regulatory pathways/networks of genes involved in drug metabolism and toxicology
      in key human tissues. We envision that the increased coverage of functional
      genetic polymorphisms, the availability of drug metabolism-centered gene
      networks, and the maturing methodologies previously developed for understanding
      complex human diseases can be applied to pharmacogenomic and toxicogenomic
      studies to further our understanding of inter-individual variability in drug
      efficacy and toxicity and eventually help direct personalized medicine.

PMID- 22591345
TI  - Detection of EGFR somatic mutations in non-small cell lung cancer (NSCLC) using a
      novel mutant-enriched liquidchip (MEL) technology.
AB  - We have developed and standardized a novel technology, mutant-enriched liquidchip
      (MEL), for clinical detection of EGFR mutations. The MEL integrates a mutant
      enriched PCR procedure with liquidchip technology for detections of EGFR exon 19
      deletions and L858R mutation on both formalin-fixed and paraffin-embedded (FFPE)
      slides and plasma samples from patients with non-small cell lung cancer (NSCLC).
      The detection sensitivity was 0.1% of mutant DNA in the presence of its wild-type
      DNA. The cross-reaction rate was lower than 5%. To evaluate the MEL platform, the
      EGFR mutation status of 59 patients with advanced NSCLC treated with EGFRTKIs
      (Tyrosine Kinase Inhibitors) were tested on their FFPE samples. EGFR exon 19
      deletions and L858R were detected in 21 patients (21/59) and 76.2% (16/21) of
      them had partial response to the EGFR-TKIs, while by sequencing method, only 4
      (4/59) mutations were detected. Plasma samples from 627 patients with various
      stages of NSCLC were examined with the MEL and 22% of EGFR exon 19 deletions and
      L858R were detected. Furthermore, in patients with advanced disease there are
      more mutations detected in plasma samples than in patients with less advanced
      disease. In conclusion, the MEL is a sensitive, stable, and robust technology for
      detecting EGFR DNA mutations from both FFPE and plasma samples from patients with
      NSCLC and is now routinely used for clinical diagnosis.

PMID- 22591346
TI  - Negatively cooperative binding properties of human cytochrome P450 2E1 with
      monocyclic substrates.
AB  - Human CYP2E1 accounts for almost 2% of total CYP enzymes in the liver cells, and
      plays a crucial role in the metabolism of small molecular weight compounds. This
      enzyme is associated with the nearly 6% metabolisms of the currently clinical
      drugs. However, it is found that CYP2E1 has a non-hyperbolic kinetic profile that
      can not be explained by the common Michaelis-Menten mechanism. Further studies
      show that the non-hyperbolic kinetic behaviors are associated with multiple
      substrate binding, which is also known as the cooperative binding properties.
      However, the detailed mechanism for the cooperative binding is not clear by now.
      In this paper, we summarized the experimental and theoretical studies on the
      cooperative binding mechanism. Based on the structural analysis, a second
      substrate binding site is confirmed in human CYP2E1, which is located neither in
      the region near Leu103, Leu210 and Phe478, nor far from the active site.
      Additionally, two important residues Thr303 and Phe478 are also identified to be
      the key factors in the cooperative binding on the short-range and long-range
      effects, respectively. The former plays a crucial role in the positioning of
      substrates and in proton delivery to the active site; the latter is located
      between the substrate access channel and the active site, and exhibits directly
      effects on substrate access or on substrate positioning in the active site. All
      these points can provide useful information for the cooperative binding in human
      CYP2E1, revealing the detailed mechanism for the non-hyperbolic kinetic
      behaviors.

PMID- 22591347
TI  - The importance of integrating SNP and cheminformatics resources to
      pharmacogenomics.
AB  - Single nucleotide polymorphisms (SNPs) are the most frequent variants in many
      genes and are promising markers in relation to drug responses in pharmacogenomics
      studies. In this review, we emphasized the importance of the cheminformatic
      related and SNP-related resources and tools and how they can improve
      pharmacogenomics studies. Currently, many cheminformatic resources are well
      developed and provide much information on drug metabolism and targeting. In
      parallel, there are also many well established SNP-related resources that are
      able to provide the information related to SNP genotyping, tag SNPs and
      functional classification. However, cheminformatic and SNP resources have not, as
      yet, been well-integrated to provide a user-friendly platform for
      pharmacogenomics studies. This paper presents a brief overview of the many
      available public resources for cheminformatics (DrugBank, PharmGKB and other
      drugrelated databases) and SNPs (dbSNP, HapMap, SNP500Cancer, SNP-RFLPing 2 and
      other SNP tools) and points out the importance of integrating cheminformatic and
      SNP resources for the future of pharmacogenomics.

PMID- 22591348
TI  - SNP web resources and their potential applications in personalized medicine.
AB  - Single nucleotide polymorphisms (SNPs) are the commonest genetic variant in the
      human genome and have been associated with inter-individual differences in drug
      response. Finding the causative SNPs underlying variations in drug response has
      been a cornerstone of personalized medicine. However, as there are over 19
      million SNPs, the task of finding causative SNPs underlying differences in drug
      response using in vitro and in vivo methods can be intimidating. SNP related web
      resources can be invaluable in the search for SNPs relevant to drug response
      phenotypes as they represent relatively cheaper yet efficient ways of
      prioritizing relevant SNPs for further study. These resources serve as
      repositories of SNP information or contain in silico tools that can predict the
      functionality of a SNP. More sophisticated resources integrate the information
      repository function with the predictive function to create a one stop SNP
      resource for researchers. SNP related web resources can also aid researchers in
      planning and analyzing different types of genetic association studies by aiding
      in selecting SNPs for genotyping in these studies. The focus of this mini review
      is to outline the SNP related web resources that are available to researchers and
      how these resources may aid researchers studying SNP-drug response phenotype
      associations. Through efficient utilization of SNP related web resources,
      researchers will hopefully be able accelerate the pace of SNP related research in
      pharmacogenomics by identifying high risk SNP variants contributing to drug
      response as well as developing novel therapeutic targets based on understanding
      how SNPs alter drug response pathways.

PMID- 22591349
TI  - The SmartAmp method: rapid detection of SNPs in thiopurine S-methyltransferase
      and ABC transporters ABCC4 and ABCG2.
AB  - Genetic polymorphisms of drug transporters as well as drug metabolizing enzymes
      have been documented to play a significant role in patients' responses to
      medication. A key requirement for advancing personalized medicine is the ability
      to rapidly and conveniently test for patients' genetic polymorphisms. We have
      recently developed a rapid and cost-effective method for single nucleotide
      polymorphism (SNP) detection, named Smart Amplification Process (SmartAmp), which
      enables us to detect genetic polymorphisms or mutations in 30 to 45 min under
      isothermal conditions without the need for DNA isolation and PCR amplification.
      This article presents the SmartAmp-based detection of SNPs in the thiopurine S
      methyltransferase gene as well as in the ATP-binding cassette (ABC) transporter
      ABCC4 and ABCG2 genes that are critically involved in drug-induced adverse
      reactions. The SmartAmp method is expected to provide a practical and cost
      effective tool for pharmacogenomics-based personalized medicine.

PMID- 22591350
TI  - Personalized medicine: potential, barriers and contemporary issues.
AB  - Personalized medicine has gained significant attention over the last decade as
      technologies for understanding biological differences between individuals have
      advanced dramatically. There are many potential benefits of personalized medicine
      including minimizing risk of drug toxicity, increasing benefit from drugs used,
      contributing to the sustainability of the healthcare system and facilitating drug
      discovery and development programs. Unfortunately there are also many barriers
      such as cost, complexity, high quality evidence requirements, and the need for
      further education that have limited the clinical translation of pharmacogenomic
      tests to date. Issues that need to be clarified are also considered, such as the
      regulatory evidence requirements for pharmacogenomic tests and the need for
      multiple pathways and for pharmacogenomic marker development. These issues
      surrounding personalized medicine are contextualized using three contemporary
      examples of pharmacogenetic tests involving drug metabolising enzymes: UDP
      glucuronosyltransferase 1A1 and irinotecan toxicity, cytochrome P450 2C19 and
      clopidogrel efficacy, and cytochrome P450 2C9 and warfarin dosing.

PMID- 22591351
TI  - Prediction and functional analysis of single nucleotide polymorphisms.
AB  - With the high speed DNA sequencing of genome, databases of genome data continue
      to grow, and the understanding of genetic variation between individuals grows as
      well. Single nucleotide polymorphisms (SNPs), the most common type of genetic
      variation, are an increasingly important resource for understanding the structure
      and function of the human genome and become a valuable resource for investigating
      the genetic basis of disease. During the past years, in addition to experimental
      approaches to characterize specific variants, intense bioinformatics techniques
      were applied to understand the effects of these genetic changes. In the genetics
      studies, one intends to understand the molecular basis of disease, and
      computational methods are becoming increasingly important for SNPs selection,
      prediction and understanding the downstream effects of genetic variation. The
      review provides systematic information on the available resources and methods for
      SNPs discovery and analysis. We also report some new results on DNA sequence
      based prediction of SNPs in human cytochrome P450, which serves as an example of
      computational methods to predict and discover SNPs. Additionally, annotation and
      prediction of functional SNPs, as well as a comprehensive list of existing tools
      and online recourses, are reviewed and described.

PMID- 22591353
TI  - Mapping the tRNA binding site on the surface of human DNMT2 methyltransferase.
AB  - The DNMT2 enzyme methylates tRNA-Asp at position C38. Because there is no tRNA
      Dnmt2 cocrystal structure available, we have mapped the tRNA binding site of
      DNMT2 by systematically mutating surface-exposed lysine and arginine residues to
      alanine and studying the tRNA methylation activity and binding of the
      corresponding variants. After mutating 20 lysine and arginine residues, we
      identified eight of them that caused large (>4-fold) decreases in catalytic
      activity. These residues cluster within and next to a surface cleft in the
      protein, which is large enough to accommodate the tRNA anticodon loop and stem.
      This cleft is located next to the binding pocket for the cofactor S-adenosyl-L
      methionine, and the catalytic residues of DNMT2 are positioned at its walls or
      bottom. Many of the variants with strongly reduced catalytic activity showed only
      a weak loss of tRNA binding or even bound better to tRNA than wild-type DNMT2,
      which suggests that the enzyme induces some conformational changes in the tRNA in
      the transition state of the methyl group transfer reaction. Manual placement of
      tRNA into the structure suggests that DNMT2 mainly interacts with the anticodon
      stem and loop.

PMID- 22591354
TI  - Ultrastrong, foldable, and highly conductive carbon nanotube film.
AB  - Preparation of strong, flexible, and multifunctional carbon-based films has
      attracted considerable interest not only in fundamental research areas but also
      for industrial applications. We report a binder-free, ultrastrong, and foldable
      carbon nanotube (CNT) film using aligned few-walled nanotube sheets drawn from
      spinnable nanotube arrays. The film exhibits tensile strengths up to ~2 GPa and a
      Young's modulus up to ~90 GPa, which is markedly superior to other types of
      carbon-based films reported, including commercial graphite foils, buckypapers,
      and graphene-related papers. The film can bear severe bending (even being folded)
      and shows good structure integrity and negligible change in electric
      conductivity. The unique structure of the CNT film (good nanotube alignment, high
      packing density) provides the film with direct and efficient transport paths for
      electricity. As a flexible charge collector, it favors a magnesium oxide coating
      to exhibit high charge/discharge rate stability and an excellent electrochemical
      capacitance close to its theoretical value.

PMID- 22591355
TI  - Counterpulsation with symphony prevents retrograde carotid, aortic, and coronary
      flows observed with intra-aortic balloon pump support.
AB  - A counterpulsation device (Symphony) is being developed to provide long-term
      circulatory support for advanced heart failure (HF) patients. In acute animal
      experiments, flow waveform patterns in the aortic, carotid, and coronary arteries
      were compared during Symphony and intra-aortic balloon pump (IABP) support. Human
      data were examined for similarities. The 30-mL Symphony was compared to a 40-mL
      IABP in calves with cardiac dysfunction (80-100 kg, n = 8). Aortic pressures and
      aortic, carotid, and coronary artery flows were simultaneously recorded at
      baseline (devices off) and during 1:1 and 1:2 support. Forward, retrograde, and
      mean flows were calculated and compared for each test condition. Findings were
      also compared to aortic flow measurements recorded in HF patients (n = 21)
      supported by 40-mL IABP. IABP caused significant retrograde flows in the aorta,
      coronary (IABP: -24 +/- 8 mL/min, Symphony: -6 +/- 2 mL/min, baseline: -2 +/- 1
      mL/min, P < 0.05), and carotid arteries (IABP: -30 +/- 5 mL/min, Symphony: -0 +/-
      0 mL/min, baseline: -0 +/- 0 L/min, P < 0.05) during ventricular systole compared
      to the Symphony. IABP support produced higher diastolic pressure and flow
      augmentation compared to Symphony. Due to retrograde flows during IABP support,
      Symphony provided higher overall coronary, carotid, and aortic flows. Similar
      reduction in total aortic flows due to retrograde flow was observed in HF
      patients during IABP support. Counterpulsation with an IABP via aortic volume
      displacement produces retrograde flows during rapid balloon deflation that
      reduces total flow. Counterpulsation with Symphony via volume removal eliminates
      retrograde flow and improves total flow more than that achieved with IABP. The
      Symphony may provide long-term hemodynamic benefits in HF patients.

PMID- 22591356
TI  - Response to antiretroviral treatment after failure of NNRTI plus NRTIs-based
      therapy. Data from the ARCA collaborative group.
AB  - OBJECTIVE: The aim of the present study was to evaluate the virological response
      to a new antiretroviral treatment (ART2) after failure of a nonnucleoside reverse
      transcriptase inhibitor (NNRTI) plus two nucleoside reverse transcriptase
      inhibitors (NRTIs)-containing regimen. DESIGN: Retrospective observational study
      based on the Italian ARCA cohort database. Adult patients were included if they
      had a virological failure (defined as plasma viral load above 500 copies/ml in
      two subsequent visits) while on a treatment with one NNRTI plus 2 NRTIs, had an
      available HIV genotype. RESULTS: Patients on ART2 were followed up for 791
      person/year and median follow up was 10.8 months(IQR 5.2-26). Variables
      associated with reduced risk of ART2 virological failure at univariable analysis
      had started the treatment in recent years (HR 0.90; 95% CI 0.86-0.94, p < 0.0001)
      and duration of previous NNRTI treatment (HR 0.995; 95%CI 0.990-0.990, p=0.045).
      Variables associated with increased risk of virological failure of ART2 were a
      higher plasma viral load (pVL) at baseline(HR 1.2; 95% CI 1.07-1.34, p=0.002) and
      the type of treatment, in particular an unboosted PI-containing regimen vs. a
      boosted PI-containing regimen(HR 1.6; 95%CI 1.25-2.04 p < 0.0001) and a non-PI
      containing vs. a boosted PI-containing regimen (HR 1.56; 95% CI 1.25-1.96, p <
      0.0001). At multivariable analysis, year of ART2 start, pVL at NNRTI failure as
      well as using a boosted PI remained statistically significant predictors.
      CONCLUSION: This study highlights the role of drugs with high genetic barrier,
      such as boosted PI as a cornerstone to build a new antiretroviral treatment in
      patients failing a NNRTI based regimen.

PMID- 22591357
TI  - Minority HIV patients' perceptions of barriers and facilitators to participation
      in clinical research.
AB  - HIV clinical trials play an essential role in producing new HIV medications,
      developing guidelines for the appropriate timing of antiretroviral treatment, and
      evaluating behavioral interventions that aim to increase the quality of life of
      HIV-infected individuals. It is critical to have participation from all
      demographic groups, yet minorities are disproportionately underrepresented in HIV
      clinical research. This study assessed HIV+ minority patient perceptions of the
      barriers and benefits of participating in HIV clinical trials in an HIV clinic of
      a large, urban teaching hospital. Twenty-six, age-eligible (18-65), minority
      patients were recruited and participated in three focus groups, separated by
      clinical research participation status. Results suggest differences in
      perceptions between those who had and had not participated. Facilitators for
      those who had participated included doctor recommendation and receiving extra
      medical attention. Those who had not participated indicated disclosure of HIV
      status, fear of losing the stability that their current medication regimen
      provided, distrust of the medical system and doubt about the origin of HIV were
      major deterrents of participation. Both groups indicated a need to better educate
      minority patients about what clinical research is and its benefits. To increase
      minority participation, it is vital to examine the perceptions of minority HIV
      infected patients and develop culturally competent, developmentally appropriate
      messages that address these barriers.

PMID- 22591358
TI  - Interleukin-7 biology in HIV disease and the path to immune reconstitution.
AB  - Interleukin-7 (IL-7) is a cytokine that plays a critical role in T cell
      homeostasis by promoting proliferation and survival of mature T cells and also by
      enhancing thymic output for the generation of new T cells. IL-7 receptor
      expression and signaling function is perturbed in HIV infection and could
      contribute to disease pathogenesis. Even though highly active anti-retroviral
      therapy has markedly reduced morbidity and mortality in HIV-infected persons,
      there remains concern that a significant proportion of treated patients may
      experience relatively poor CD4+ T cell recovery despite sustained viral
      suppression. Recent human trials and animal studies suggest that IL-7
      administration may provide a powerful tool to enhance T cell reconstitution in
      HIV-infected persons. The role of IL-7/IL-7 receptor perturbations in HIV
      pathogenesis and the potential to reconstitute immunity with IL-7 administration
      in the setting of HIV infection are important areas of investigation.

PMID- 22591360
TI  - HIV and substance abuse: a commentary.

PMID- 22591359
TI  - Effectiveness of antiretroviral therapy in HIV-1-infected active drug users
      attended in a drug abuse outpatient treatment facility providing a
      multidisciplinary care strategy.
AB  - OBJECTIVE: HIV-1-infected active drug users (ADU) obtain smaller clinical
      benefits with antiretroviral therapy (HAART) compared to non-ADU subjects with
      sexually-transmitted HIV-1 infection. Therefore treatment strategies are required
      to address the specific issues arising in this challenging scenario. We describe
      the effectiveness of HAART provided in a drug abuse outpatient treatment facility
      through a comprehensive integrated care that includes medical, drug dependence,
      and psychosocial support. METHODS: We included all consecutive HIV-1-infected ADU
      admitted for drug dependency treatment and who started their first HAART. A
      comparator arm consisted of a control group of sexually transmitted HIV-1
      infected subjects attended in a reference hospital under standard care. The
      strategy did not include directly observed treatment. RESULTS: A total of 71 ADU
      and 48 matched subjects infected through sexual transmission were included. ADU
      had lower baseline CD4+ T-cell counts (196 vs 279 cells/MUL, P=.001), and more
      advanced CDC stages (P=.001). The estimated probabilities of patients with
      virological response ( < 50 copies/mL) at weeks 48 and 96 were 92.9% (95%-CI:
      87.1%-99.1%) and 87.3% (95%-CI: 78.7%-95.2% for ADU, and 93.7%(95%-CI: 84.1%
      99.8%) and 87.5% (95%-CI: 77.5%-97.3%) for sexually-infected subjects (P= .1325
      and .241). Kaplan-Meier estimates of time to loss of virological response did not
      show differences between groups (log rank test, P=.965). CONCLUSIONS: An
      integrated multidisciplinary care of HIV-1-infected antiretroviral naive ADU
      provided in a drug abuse treatment center obtains high rates of virological
      suppression, similar to those observed in a comparison group of sexually
      transmitted HIV-1-infected subjects. This strategy should be further evaluated in
      public health programs and assessed in randomized trials.

PMID- 22591361
TI  - HIV-1 gp120 and drugs of abuse: interactions in the central nervous system.
AB  - HIV-1 infection is a global public health problem with more than 34 million
      people living with HIV infection. Although great strides have been made in
      treating this epidemic with therapeutic agents, the increase in patient life span
      has been coincident with an increase in the prevalence of HIV-associated
      neurocognitive disorders (HAND). HAND is thought to result from the neurotoxic
      effects of viral proteins that are shed from HIV-infected microglial cells. One
      of the primary neurotoxins responsible for this effect is the HIV-1 glycoprotein
      gp120. Exposure of neurons to gp120 has been demonstrated to cause apoptosis in
      neurons, as well as numerous indirect effects such as an increase in inflammatory
      cytokines, an increase in oxidative stress, and an increase in permeability of
      the blood-brain barrier. In many patients, the use of drugs of abuse (DOA)
      exacerbates the neurotoxic effects of gp120. Cocaine, methamphetamine and
      morphine are three DOAs that are commonly used by those infected with HIV-1. All
      three of these DOAs have been demonstrated to increase oxidative stress in the
      CNS as well as to increase permeability of the blood-brain barrier. Numerous
      model systems have demonstrated that these DOAs have the capability of
      exacerbating the neurotoxic effects of gp120. This review will summarize the
      neurotoxic effects of gp120, the deleterious effects of cocaine, methamphetamine
      and morphine on the CNS, and the combined effects of gp120 in the context of
      these drugs.

PMID- 22591362
TI  - Matrix metalloproteinase dependent cleavage of cell adhesion molecules in the
      pathogenesis of CNS dysfunction with HIV and methamphetamine.
AB  - Physiologically appropriate levels of matrix metalloproteinases (MMPs) are likely
      important to varied aspects of CNS function. In particular, these enzymes may
      contribute to neuronal activity dependent synaptic plasticity and to cell
      mobility in processes including stem cell migration and immune surveillance.
      Levels of MMPs may, however, be substantially increased in the setting of HIV
      infection with methamphetamine abuse. Elevated MMP levels might in turn influence
      integrity of the blood brain barrier, as has been demonstrated in published work.
      Herein we suggest that elevated levels of MMPs can also contribute to microglial
      activation as well as neuronal and synaptic injury through a mechanism that
      involves cleavage of specific cell and synaptic adhesion molecules.

PMID- 22591363
TI  - HIV-1, methamphetamine and astrocyte glutamate regulation: combined excitotoxic
      implications for neuro-AIDS.
AB  - Glutamate, the most abundant excitatory transmitter in the brain can lead to
      neurotoxicity when not properly regulated. Excitotoxicity is a direct result of
      abnormal regulation of glutamate concentrations in the synapse, and is a common
      neurotoxic mediator associated with neurodegenerative disorders. It is well
      accepted that methamphetamine (METH), a potent central nervous stimulant with
      high abuse potential, and human immunodeficiency virus (HIV)-1 are implicated in
      the progression of neurocognitive malfunction. Both have been shown to induce
      common neurodegenerative effects such as astrogliosis, compromised blood brain
      barrier integrity, and excitotoxicity in the brain. Reduced glutamate uptake from
      neuronal synapses likely leads to the accumulation of glutamate in the
      extracellular spaces. Astrocytes express the glutamate transporters responsible
      for majority of the glutamate uptake from the synapse, as well as for vesicular
      glutamate release. However, the cellular and molecular mechanisms of astrocyte
      mediated excitotoxicity in the context of METH and HIV-1 are undefined. Topics
      reviewed include dysregulation of the glutamate transporters, specifically
      excitatory amino acid transporter-2, metabotropic glutamate receptor(s)
      expression and the release of glutamate by vesicular exocytosis. We also discuss
      glutamate concentration dysregulation through astrocytic expression of enzymes
      for glutamate synthesis and metabolism. Lastly, we discuss recent evidence of
      various astrocyte and neuron crosstalk mechanisms implicated in glutamate
      regulation. Astrocytes play an essential role in the neuropathologies associated
      with METH/HIV-1-induced excitotoxicity. We hope to shed light on common cellular
      and molecular pathways astrocytes share in glutamate regulation during drug abuse
      and HIV-1 infection.

PMID- 22591364
TI  - Modulation of intracellular restriction factors contributes to methamphetamine
      mediated enhancement of acquired immune deficiency syndrome virus infection of
      macrophages.
AB  - Epidemiological studies have demonstrated that the use of methamphetamine (METH),
      a sympathomimetic stimulant, is particularly common among patients infected with
      HIV. In vitro studies have determined that METH enhances HIV infection of CD4+ T
      cells, monocyte-derived dendritic cells, and macrophages. In addition, animal
      studies have also showed that METH treatment increases brain viral load of SIV
      infected monkeys and promotes HIV replication and viremia in HIV/hu-CycT1
      transgenic mice. However, the mechanisms (s) of METH actions on HIV remain to be
      determined. In this study, we investigated the impact of METH on intracellular
      restriction factors against HIV and SIV. We demonstrated that METH treatment of
      human blood mononuclear phagocytes significantly affected the expression of anti
      HIV microRNAs and several key elements (RIG-I, IRF-3/5, SOCS-2, 3 and PIAS-1, 3,
      X, Y) in the type I IFN pathway. The suppression of these innate restriction
      factors was associated with a reduced production of type I IFNs and the
      enhancement of HIV or SIV infection of macrophages. These findings indicate that
      METH use impairs intracellular innate antiviral mechanism(s) in macrophages,
      contributing to cell susceptibility to the acquired immune deficiency syndrome
      (AIDS) virus infection.

PMID- 22591365
TI  - Adolescent HIV-1 transgenic rats: evidence for dopaminergic alterations in
      behavior and neurochemistry revealed by methamphetamine challenge.
AB  - Since the introduction of combination antiretroviral therapy (cART) in the mid
      90s, the most severe forms of HIV-1-associated neurocognitive disorders (HAND)
      have diminished. However, milder forms of HAND remain prevalent. Basic and
      clinical studies implicate alterations in the dopaminergic (DAergic) system in
      HIV-1 infection. We used the Fischer 344 HIV-1 transgenic (HIV-1 Tg) rat, which
      expresses 7 of the 9 HIV-1 genes, to examine potential DAergic alterations.
      Animals were studied beginning at 35 days of age to assess early-onset DAergic
      alterations, well before any documented neurological symptoms or clinical signs
      of "wasting". At 48 hr intervals, animals were administered a single dose of
      methamphetamine (METH) (0, 0.5, 1, 2.5 and 5 mg/kg/ml s.c.) and tested for the
      auditory startle response (ASR) and prepulse inhibition (PPI), using an auditory
      prepulse [85 dB(A) broad-band noise stimulus] and an auditory startle stimulus
      [100 dB(A) broad-band noise stimulus] in a sound-attenuating chamber with a
      continuous 70 dB(A) white noise background. The protocol used a 5-min acclimation
      period, 6 startle trials, and 36 PPI trials [ISIs of 0, 8, 40, 80, 120, and 4000
      ms, 6-trial blocks, Latin square design]. As the dose of METH increased, PPI of
      the startle response decreased. The HIV-1 Tg rats displayed a greater dose
      dependency to the METH-induced disruption of PPI compared to non-transgenic
      controls. Western blot analysis of midbrain extracts revealed lower tyrosine
      hydroxylase (TH) protein levels and higher monoamine oxidase A (MAO-A) protein
      levels in HIV-1 Tg rats treated with METH compared to non-transgenic controls.
      Early-detected cognitive alterations in the preattentive process of sensorimotor
      gating may have significant predictive utility regarding the progression of
      DAergic alterations in HIV-1 infection.

PMID- 22591366
TI  - Cocaine and HIV-1 interplay in CNS: cellular and molecular mechanisms.
AB  - Although antiretrovirals are the mainstay of therapy against HIV infection,
      neurological complications associated with the virus continue to hamper quality
      of life of the infected individuals. Drugs of abuse in the infected individuals
      further fuel the epidemic. Epidemiological studies have demonstrated that abuse
      of cocaine resulted in acceleration of HIV infection and the progression of
      NeuroAIDS. Cocaine has not only been shown to play a crucial role in promoting
      virus replication, but also has diverse but often deleterious effects on various
      cell types of the CNS. In the neuronal system, cocaine exposure results in
      neuronal toxicity and also potentiates gp120-induced neurotoxicity. In the
      astroglia and microglia, cocaine exposure leads to up-regulation of pro
      inflammatory mediators such as cytokines and chemokines. These in turn, can lead
      to neuroinflammation and transmission of toxic responses to the neurons.
      Additionally, cocaine exposure can also lead to leakiness of the blood-brain
      barrier that manifests as enhanced transmigraiton of leukocytes/monocytes into
      the CNS. Both in vitro and in vivo studies have provided valuable tools in
      exploring the role of cocaine in mediating HIV-associated neuropathogenesis. This
      review summarizes previous studies on the mechanism(s) underlying the interplay
      of cocaine and HIV as it relates to the CNS.

PMID- 22591367
TI  - Differential regulation of neurotoxin in HIV clades: role of cocaine and
      methamphetamine.
AB  - Studies have demonstrated that infection with HIV-1 (subtypes) clades might
      differentially contribute to HIV- 1-associated neuro cognitive disorder (HAND).
      Substance abuse and illicit drugs such as cocaine and methamphetamine (METH) are
      also known to play a role in neuronal impairments. Neurotoxin quinolinic acid
      (QUIN) and arachidonic acid (AA) metabolites are regulators of central nervous
      system (CNS) functions. These neurotoxins are dysregulated during HIV infection,
      and substance abuse exacerbates immune and neuronal dysfunctions, leading to
      dementia and neurocognitive impairments. Studies have demonstrated an association
      between HIV infection and substance abuse in terms of viral replication and
      disease progression in Neuro-AIDS. In this review, we briefly discuss the effect
      of cocaine and METH, and differential role of HIV-1 B and C induced indoleamine
      2, 3-dioxygenase (IDO) and cyclooxygenase-2 (COX-2) mediated induction of
      neurotoxin QUIN and AA metabolites that implicate neuronal dysfunctions.

PMID- 22591369
TI  - Effects of opiates and HIV proteins on neurons: the role of ferritin heavy chain
      and a potential for synergism.
AB  - Human immunodeficiency virus 1 (HIV-1) and its associated proteins can have a
      profound impact on the central nervous system. Co-morbid abuse of opiates, such
      as morphine and heroin, is often associated with rapid disease progression and
      greater neurological dysfunction. The mechanisms by which HIV proteins and
      opiates cause neuronal damage on their own and together are unclear. The
      emergence of ferritin heavy chain (FHC) as a negative regulator of the chemokine
      receptor CXCR4, a co-receptor for HIV, may prove to be important in elucidating
      the interaction between HIV proteins and opiates. This review summarizes our
      current knowledge of central nervous system damage inflicted by HIV and opiates,
      as well as the regulation of CXCR4 by opiate-induced changes in FHC protein
      levels. We propose that HIV proteins and opiates exhibit an additive or
      synergistic effect on FHC/CXCR4, thereby decreasing neuronal signaling and
      function.

PMID- 22591370
TI  - Effects of vitamin A deficiency and opioids on parvalbumin + interneurons in the
      hippocampus of the HIV-1 transgenic rat.
AB  - Opioid use in HIV infection has been associated with an increased frequency of
      neurological disease and cognitive impairment and vitamin A deficiency has been
      linked to progressive HIV disease in drug users. In this report the potential
      effects of these factors, alone and in combination, on gamma amino butyric acid
      (GABA)-expression interneurons in hippocampus in the HIV-1 transgenic rat (TG)
      model were studied. TG and wild-type (WT) F344 Fisher rats deficient in vitamin A
      from birth were implanted either with a 37.5 mg morphine tablet or with a
      matching placebo and total numbers of neurons and of parvalbumin+ neurons were
      quantitated and parvalbumin expression was quantitated in the CA1 hippocampal
      region of the rats. These studies showed that total neuronal numbers were
      decreased in the TG versus WT Fisher rats and that this decrease was enhanced by
      the vitamin A deficient diet and by treatment with morphine. In contrast, there
      was no significant change noted in numbers of parvalbumin+ neurons. However,
      levels of parvalbumin expression were decreased for vitamin A deficient and
      morphine-treated WT rats as compared to WT rats on the normal diet and placebo
      treated WT rats. For TG rats, parvalbumin expression was higher for vitamin A
      deficient TG rats treated with either placebo or morphine than for WT vitamin A
      deficient rats treated with placebo, and placebo treated vitamin A deficient TG
      rats showed higher expression than morphine treated vitamin A deficient rats.
      Expression was also higher for vitamin A deficient morphine-treated rats than for
      the corresponding WT rat groups and for vitamin A deficient TG rats treated with
      placebo. For the remaining groups, parvalbumin was similar for the TG and WT
      rats. These findings suggest that in hippocampus vitamin A deficiency and
      morphine can increase parvalbumin expression, perhaps as a manifestation of a
      stress response. Parvalbumin-expressing GABA-ergic interneurons regulate the
      primary neuronal output from hippocampus that is important for memory and
      behavior. Therefore, these studies suggest that vitamin A deficiency and morphine
      might have effects that may impact such outputs and thereby have lasting effects
      on cognitive status.

PMID- 22591368
TI  - Opiate drug use and the pathophysiology of neuroAIDS.
AB  - Opiate abuse and HIV-1 have been described as interrelated epidemics, and even in
      the advent of combined anti-retroviral therapy, the additional abuse of opiates
      appears to result in greater neurologic and cognitive deficits. The central
      nervous system (CNS) is particularly vulnerable to interactive opiate-HIV-1
      effects, in part because of the unique responses of microglia and astroglia.
      Although neurons are principally responsible for behavior and cognition, HIV-1
      infection and replication in the brain is largely limited to microglia, while
      astroglia and perhaps glial progenitors can be latently infected. Thus, neuronal
      dysfunction and injury result from cellular and viral toxins originating from HIV
      1 infected/exposed glia. Importantly, subsets of glial cells including
      oligodendrocytes, as well as neurons, express u-opioid receptors and therefore
      can be direct targets for heroin and morphine (the major metabolite of heroin in
      the CNS), which preferentially activate u-opioid receptors. This review
      highlights findings that neuroAIDS is a glially driven disease, and that opiate
      abuse may act at multiple glial-cell types to further compromise neuron function
      and survival. The ongoing, reactive cross-talk between opiate drug and HIV-1 co
      exposed microglia and astroglia appears to exacerbate critical proinflammatory
      and excitotoxic events leading to neuron dysfunction, injury, and potentially
      death. Opiates enhance synaptodendritic damage and a loss of synaptic
      connectivity, which is viewed as the substrate of cognitive deficits. We
      especially emphasize that opioid signaling and interactions with HIV-1 are
      contextual, differing among cell types, and even within subsets of the same cell
      type. For example, astroglia even within a single brain region are heterogeneous
      in their expression of u-, delta-, and kappa-opioid receptors, as well as CXCR4
      and CCR5, and Toll-like receptors. Thus, defining the distinct targets engaged by
      opiates in each cell type, and among brain regions, is critical to an
      understanding of how opiate abuse exacerbates neuroAIDS.

PMID- 22591371
TI  - Mechanism(s) involved in opioid drug abuse modulation of HAND.
AB  - Drug abuse and HIV infection are interlinked. From the onset of the HIV/AIDS
      epidemic, the impact of illicit drug use on HIV disease progression has been a
      focus of many investigations. Both laboratory-based and epidemiological studies
      strongly indicate that drug abuse may exacerbate HIV disease progression and
      increase mortality and morbidity in these patients. Increase susceptibility to
      opportunistic infection has been implicated as one of the major causes for this
      detriment. Furthermore, opioids are known to elicit prevalence of
      neurodegenerative disorders in HIV-infected patients. Numerous authors have
      delineated various molecular as well as cellular mechanisms associated with
      neurological complications in these patients. This review gives an overview of
      these findings. Understanding the mechanisms will allow for the development of
      targeted therapies aimed at reducing the progression of neurocognitive decline in
      the drug abusing HIV infected individuals.

PMID- 22591372
TI  - Circulating tumour cells escape from EpCAM-based detection due to epithelial-to
      mesenchymal transition.
AB  - BACKGROUND: Circulating tumour cells (CTCs) have shown prognostic relevance in
      metastatic breast, prostate, colon and pancreatic cancer. For further development
      of CTCs as a biomarker, we compared the performance of different protocols for
      CTC detection in murine breast cancer xenograft models (MDA-MB-231, MDA-MB-468
      and KPL-4). Blood samples were taken from tumour bearing animals (20 to 200 mm2)
      and analysed for CTCs using 1. an epithelial marker based enrichment method
      (AdnaTest), 2. an antibody independent technique, targeting human gene
      transcripts (qualitative PCR), and 3. an antibody-independent approach, targeting
      human DNA-sequences (quantitative PCR). Further, gene expression changes
      associated with epithelial-to-mesenchymal transition (EMT) were determined with
      an EMT-specific PCR assay. METHODS: We used the commercially available Adna Test,
      RT-PCR on human housekeeping genes and a PCR on AluJ sequences to detect CTCs in
      xenografts models. Phenotypic changes in CTCs were tested with the commercially
      available "Human Epithelial to Mesenchymal Transition RT-Profiler PCR Array".
      RESULTS: Although the AdnaTest detects as few as 1 tumour cell in 1 ml of mouse
      blood spiking experiments, no CTCs were detectable with this approach in vivo
      despite visible metastasis formation. The presence of CTCs could, however, be
      demonstrated by PCR targeting human transcripts or DNA-sequences - without
      epithelial pre-enrichment. The failure of CTC detection by the AdnaTest resulted
      from downregulation of EpCAM, whereas mesenchymal markers like Twist and EGFR
      were upregulated on CTCs. Such a change in the expression profile during
      metastatic spread of tumour cells has already been reported and was linked to a
      biological program termed epithelial-mesenchymal transition (EMT). CONCLUSIONS:
      The use of EpCAM-based enrichment techniques leads to the failure to detect CTC
      populations that have undergone EMT. Our findings may explain clinical results
      where low CTC numbers have been reported even in patients with late metastatic
      cancers. These results are a starting point for the identification of new markers
      for detection or capture of CTCs, including the mesenchymal-like subpopulations.

PMID- 22591373
TI  - Unilateral headache with visual aura from a Wallenberg syndrome.

PMID- 22591374
TI  - Dehydration stress-induced oscillations in LEA protein transcripts involves
      abscisic acid in the moss, Physcomitrella patens.
AB  - * Physcomitrella patens is a bryophyte belonging to early diverging lineages of
      land plants following colonization of land in the Ordovician period. Mosses are
      typically found in refugial habitats and can experience rapidly fluctuating
      environmental conditions. The acquisition of dehydration tolerance by bryophytes
      is of fundamental importance as they lack water-conducting tissues and are
      generally one cell layer thick. * Here, we show that dehydration induced
      oscillations in the steady-state transcript abundances of two group 3 late
      embryogenesis abundant (LEA) protein genes in P. patens protonemata, and that the
      amplitudes of these oscillations are reflective of the severity of dehydration
      stress. * Dehydration stress also induced elevations in the concentrations of
      abscisic acid (ABA), and ABA alone can also induce dosage-dependent oscillatory
      increases in the steady-state abundance of LEA protein transcripts. Additionally,
      removal of ABA resulted in rapid attenuation of these oscillatory increases. *
      Our data demonstrate that dehydration stress-regulated expression of LEA protein
      genes is temporally dynamic and highlight the importance of oscillations as a
      robust mechanism for optimal responses. Our results suggest that dehydration
      stress-induced oscillations in the steady-state abundance of LEA protein
      transcripts may constitute an important cellular strategy for adaptation to life
      in a constantly changing environment.

PMID- 22591375
TI  - Generation and clonal isolation of retinal stem cells from human embryonic stem
      cells.
AB  - Retinal stem cells (RSCs) are present within the pigmented ciliary epithelium
      (CE) of the adult human eye and produce progeny that differentiate in vitro into
      all neural retinal subtypes and retinal pigmented epithelium (RPE). We
      hypothesized that a RSC population, similar to the adult CE-derived RSC, is
      contained within pigmented colonies that arise in long-term cultures of human
      embryonic stem cells (hESCs) suggested to recapitulate retinal development in
      vitro. Single pigmented hESC-derived cells were isolated and plated in serum-free
      media containing growth factors and, after 2 weeks, clonal sphere colonies
      containing both pigmented and non-pigmented cells were observed. These colonies
      expressed the early retinal transcription factors Rx, Chx10 and Pax6, and could
      be dissociated and replated as single cells to form secondary clonal colonies.
      When allowed to differentiate, expression of markers for both RPE and neurons was
      observed. Rhodopsin expression was detected after explant co-culture and
      transplantation into the developing mouse eye as well as following treatment with
      soluble factors in vitro. We show that RSCs emerge in an in vitro model of
      retinal development and are a potential source of human photoreceptors for use in
      transplantation.

PMID- 22591376
TI  - Angiolymphoid hyperplasia with eosinophilia treated successfully with imiquimod.

PMID- 22591377
TI  - Molecular simulation of hydrophobin adsorption at an oil-water interface.
AB  - Hydrophobins are small, amphiphilic proteins expressed by strains of filamentous
      fungi. They fulfill a number of biological functions, often related to adsorption
      at hydrophobic interfaces, and have been investigated for a number of
      applications in materials science and biotechnology. In order to understand the
      biological function and applications of these proteins, a microscopic picture of
      the adsorption of these proteins at interfaces is needed. Using molecular
      dynamics simulations with a chemically detailed coarse-grained potential, the
      behavior of typical hydrophobins at the water-octane interface is studied.
      Calculation of the interfacial adsorption strengths indicates that the adsorption
      is essentially irreversible, with adsorption strengths of the order of 100 k(B)T
      (comparable to values determined for synthetic nanoparticles but significantly
      larger than small molecule surfactants and biomolecules). The protein structure
      at the interface is unchanged at the interface, which is consistent with the
      biological function of these proteins. Comparison of native proteins with
      pseudoproteins that consist of uniform particles shows that the surface structure
      of these proteins has a large effect on the interfacial adsorption strengths, as
      does the flexibility of the protein.

PMID- 22591378
TI  - Interactions of amino acids and polypeptides with metal oxide nanoparticles
      probed by fluorescent indicator adsorption and displacement.
AB  - The adsorption of polypeptides containing an N-terminal tryptophan (Trp) residue
      attached to a hexa-backbone of alanine, serine, lysine, histidine, and aspartate
      was investigated by monitoring the fluorescence response of the Trp chromophore
      upon titration with metal oxide nanoparticles (MOx-NPs: CuO, Co(3)O(4), TiO(2),
      MgO, and CeO(2)). After correction for light-scattering effects, a strong static
      fluorescence quenching was observed upon addition of CuO and Co(3)O(4) to the
      peptides. The interaction of MOx-NPs with the peptides was assigned to an
      adsorption of the peptide backbone on the nanoparticle surface. The method was
      refined using a derivatized amino acid, 5-fluoro-Trp (5F-Trp), which resulted in
      a stronger fluorescence response. The use of the fluorescent amino acid labels
      allowed the direct assessment of the adsorption propensities of Trp-containing
      peptides in dependence on the backbone, which was verified by zeta-potential
      measurements. Moreover, upon addition of different analytes to nanoparticles with
      preadsorbed Trp-containing polypeptides, adsorption propensities of the analytes
      were assessed by an indicator displacement strategy; that is, addition of
      increasing amounts of analyte resulted in a continuous fluorescence
      enhancement/recovery. This method afforded adsorption propensities for several
      analytes. The relative binding constants for the MOx-NPs, obtained from the
      competitive titrations, varied by more than 6 orders of magnitude for CuO (5F
      TrpHis(6)-NH(2) > TrpAsp(6)-NH(2), TrpSer(6)-NH(2) > TrpLys(6)-NH(2), Trp, 5F-Trp
      > TrpAla(6)-NH(2)) but only 4 for Co(3)O(4) (TrpHis(6)-NH(2), TrpAsp(6)-NH(2) ?
      TrpLys(6)-NH(2), TrpAla(6)-NH(2), TrpSer(6)-NH(2), Trp, 5F-Trp). The study
      reveals that MOx-NPs adsorb biomolecular analytes with high selectivity, which
      has immediate implications for their applications in protein purification, drug
      delivery, and, potentially, for the assessment of their toxicology.

PMID- 22591379
TI  - Influence of nanocoated calcium phosphate on two different types of implant
      surfaces in different bone environment: an animal study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the osseointegration of two
      different types of surfaces, smooth and roughened surface implants nanocoated
      with calcium phosphate (CAP) around different bone environment. MATERIALS AND
      METHODS: Five male mongrel dogs were used in this study. The premolars and molars
      were extracted on both sides of the mandible. Eight weeks after extraction,
      implants were submerged on both sides of the mandible. On the left, CAP
      nanocoated roughened surface (RCAP) implants were installed whereas, the CAP
      nanocoated smooth surface (SCAP) implants were installed on the right side. The
      control group had no defect, on the other hand, three-wall intrabony defects were
      surgically created adjacent to the implant in the experimental group. The dogs
      were sacrificed after 12 weeks. RESULTS: Histological and histomorphometrical
      analysis were performed with the specimen. The SCAP and RCAP implants showed good
      osseointegration with no statistical significance in the control group.
      Histologically, the SCAP group showed little resolution of the defect compared
      with the RCAP group. In the experimental groups, there was a significant
      difference in defect fill between SCAP and RCAP. CONCLUSION: Within the limits of
      our study, it can be concluded that SCAP and RCAP implants show no difference in
      sufficient bone area whereas, CAP nanocoating on roughened implant surface may
      enhance osseointegration in deficient bone environment.

PMID- 22591380
TI  - A service user-initiated project investigating the attitudes of mental health
      staff towards clients and services in an acute mental health unit.
AB  - Mental Health Service Users (MHSU) are becoming increasingly recognized as very
      valuable contributors to the research process. The current study originated from
      the idea of a group of MHSU within a service user and carer research group. They
      wanted to investigate the attitudes of mental health staff towards clients in an
      acute mental health setting, as well as their attitudes towards certain aspects
      of service. An amended version of the 'Attitudes Towards Acute Mental Health
      Scale' was sent to nursing and allied staff at an acute psychiatric unit within
      the Gloucestershire 2gether NHS Foundation Trust. Fifty-seven of the 200
      anonymous questionnaires were returned. Generally positive opinions of MHSU were
      obtained, but there were divided opinions on questions regarding the aetiology of
      mental health problems (e.g. social vs. genetic determinants). Opinions on
      aspects of the admissions process, therapeutic aspects of care, the use of
      medication and the use of control and restraint techniques were also obtained.
      Demographic variables of staff age, status and years of experience in mental
      health were found to be associated with attitudes and opinions. This MHSU
      initiated study has extended the literature on mental health staff attitudes
      towards clients and services in an acute mental health setting. This study is
      split into two parts, Part A is focused on the process of involving MHSU in this
      project, Part B is concerned with the empirical investigation.

PMID- 22591381
TI  - 4D electron microscopy visualization of anisotropic atomic motions in carbon
      nanotubes.
AB  - We report the anisotropic atomic expansion dynamics of multi-walled carbon
      nanotubes, using 4D electron microscopy. From time-resolved diffraction on the
      picosecond to millisecond scale, following ultrafast heating at the rate of
      10(13) K/s, it is shown that nanotubes expand only in the radial (intertubule)
      direction, whereas no significant change is observed in the intratubular axial or
      equatorial dimensions. The non-equilibrium heating occurs on an ultrafast time
      scale, indicating that the anisotropy is the result of an efficient electron
      lattice coupling and is maintained up to equilibration. The recovery time, which
      measures the heat dissipation rate for equilibration, was found to be on the
      order of ~100 MUs. This recovery is reproduced theoretically by considering the
      composite specimen-substrate heat exchange.

PMID- 22591382
TI  - Analysis of inland crude oil spill threats, vulnerabilities, and emergency
      response in the midwest United States.
AB  - Although coastal oil spills tend to be highly publicized, crude oil spills in the
      United States affect inland areas relatively often. Spills to inland areas often
      affect sensitive environments and can have greater impacts to health and welfare
      than spills to coastal areas. For these reasons, the authors investigated inland
      crude oil spill threats, vulnerabilities, and emergency response in the
      midwestern U.S. states of Illinois, Indiana, Michigan, Minnesota, Ohio, and
      Wisconsin. These states work with the Region 5 Offices of the U.S. Environmental
      Protection Agency. Region 5's geospatial data in the Inland Sensitivity Atlas
      were turned into metrics indicating inland crude oil spill threats and
      vulnerabilities among the Region's sub-watersheds. These threats and
      vulnerabilities were weighted using data from the National Response Center and
      the Department of Energy's Environmental Restoration Priority System. The
      locations of the Region's emergency responders were geocoded in GIS. The GIS
      calculated the emergency response times to the Region's sub-watersheds. The
      resulting scatter plots are connected to the sub-watersheds in the map so
      stakeholders can (1) see the outlying sub-watersheds of concern and (2) better
      understand how reducing threats and better response time can reduce the risk of
      inland crude oil spills.

PMID- 22591383
TI  - Microenvironmental interactions in chronic lymphocytic leukemia: hints for
      pathogenesis and identification of targets for rational therapy.
AB  - Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease
      characterized by the accumulation/expansion of a clonal population of small
      mature B lymphocytes in blood, bone marrow, and lymphoid organs. Although initial
      genetic events are considered primarily responsible for the first step(s) of
      neoplastic transformation, the development and progression of the CLL clone are
      thought to be affected by various micro-environmental signals that regulate
      proliferation and survival of malignant B cells. In the present review, we focus
      on specific interactions of CLL cells with the microenvironmental component, as
      they occur through the usage by CLL cells of specific molecular structures whose
      expression has been associated with prognosis, including: i) interactions of CLL
      cells via the surface BCR and dependent on specific molecular features of the BCR
      itself and/or the presence of the BCR-associated molecule ZAP- 70; ii) non-BCR
      dependent proliferative and/or pro-survival interactions of CLL cells by CD49d
      and CD38. An overview of the putative drugs that could be employed to target
      specific molecules involved in CLL cells/tumor microenvironment interactions is
      also proposed in the closing chapter of the review.

PMID- 22591384
TI  - Chronic lymphocytic leukemia therapy: beyond chemoimmunotherapy.
AB  - Chemoimmunotherapy is the new gold standard of therapy for patients with advanced
      chronic lymphocytic leukemia (CLL). However, in spite of the high complete
      response rate achieved with chemoimmunotherapy, all patients eventually relapse
      and CLL is still incurable. Newer and more rationally developed compounds are
      clearly needed for these patients, in particular those with refractory disease.
      Among these agents, novel monoclonal antibodies, cyclin-dependent kinase
      inhibitors, chromokine receptor antagonists, lenalidomide, signal transduction
      inhibitors and pro-apoptotic molecules have recently shown some efficacy in
      patients with relapsed or refractory disease. Hopefully, the combined use of
      these agents in risk-adapted treatment strategies will improve the outcome of
      patients with CLL and set the stage for their cure.

PMID- 22591385
TI  - Immune dysfunction in chronic lymphocytic leukemia: the role for immunotherapy.
AB  - A key feature of the clinical course of chronic lymphocytic leukemia (CLL) is
      that it induces a state of immunosuppression, causing increased susceptibility to
      infections and failure of anti-tumor immune responses. Cytotoxic chemotherapy
      still forms the mainstay of most current treatment regimens, but is not curative,
      and its lack of specificity means that it also targets normal immune cells,
      exacerbating this immunosuppression. This can result in effective treatments
      being limited by infectious complications, particularly in the elderly who
      comprise the majority of patients with this disease. Immunotherapy potentially
      offers a way out of this dilemma, due to its improved specificity and ability to
      enhance immune responses to both the tumor and infectious agents. There has been
      a dramatic increase in the range of available immunotherapeutic options over the
      past decade, and many are now in the process of making the transition to the
      clinic. This review will discuss both the immune defect in CLL, and emerging
      immunotherapies, including CD40 ligand gene therapy, lenalidomide, CLL vaccines,
      CXCR4 antagonists, and adoptive cellular immunotherapies such as chimeric antigen
      receptor modified T-cells.

PMID- 22591386
TI  - Novel insights in molecular mechanisms of CLL.
AB  - B-cell chronic lymphocytic leukemia (CLL), the most common leukemia, originates
      from an expansion of a rare population of CD5+CD19+ mature B-cells. CLL occurs in
      two forms, aggressive and indolent. For the most part aggressive CLL shows high
      ZAP-70 expression and unmutated IgH V(H), while indolent CLL is characterized by
      low ZAP-70 expression and mutated IgH V(H). Despite detailed studies of clinical
      features and chromosomal abnormalities in CLL, molecular details underlying
      disease development are still not entirely clear. In the past several years, more
      and more such mechanisms have emerged. Recent studies clarified mechanistic
      details of how activation of TCL1, a critical molecule in aggressive CLL,
      initiates this malignancy. In indolent CLL characterized by 13q14 deletions, MiR
      15/16 targeting BCL2 and MCL1 and DLEU7 targeting TNF pathway were proposed as
      tumor suppressors. Analysis of CLL coding genome identified NOTCH1 as a frequent
      target of activating mutations. Interestingly most of these pathways have
      downstream activating effects on the NF-kB family transcription factors. Several
      mouse models of CLL, confirmed importance of these pathways in the pathogenesis
      of CLL. Here, we discuss what has been learned from these new pathways, and
      analyze how CLL mouse models confirm newly discovered molecular mechanisms of
      CLL.

PMID- 22591387
TI  - Purine nucleoside analogs in the treatment of rarer chronic lymphoid leukemias.
AB  - Purine nucleoside analogues (PNA) are the cytotoxic agents highly active in the
      treatment of indolent lymphoid malignancies. These drugs have chemical structure
      similar to adenosine or deoxyadenosine. PNAs are characterized by a similar
      mechanism of cytotoxicity both in proliferating and quiescent cells, such as
      inhibition of DNA synthesis, inhibition of DNA repair and accumulation of DNA
      strand breaks. In addition, PNAs induce apoptosis which is the end-point of their
      action. Older PNAs, pentostatin (DCF; 2'- deoxycoformycin), cladribine (2-CdA; 2
      chloro-2'-deoxyadenosine) and fludarabine (2-fluoro-9-(-D-arabinosyl)-adenine)
      were approved by Food and Drug Administration (FDA) for the treatment of
      hematological malignancies. In addition three novel PNAs: clofarabine (CAFdA),
      nelarabine (ara-G) and forodesine (immucillin H, BCX-1777) have been synthesized
      and introduced into preclinical studies and clinical trials. This review
      summarizes current knowledge on the mechanism of action and pharmacokinetic
      properties of older and new PNAs. Clinical activity and toxicity of PNAs,
      especially in hairy cell leukemia (HCL), hairy cell leukemia variant (HCL-V),
      prolymphocytic leukemia (PLL) and other rarer chronic lymphoid leukemias, are
      also presented. 2-CdA and DCF, introduced in the 1980s, changed radically the
      treatment modality, inducing complete and durable responses in the majority of
      patients with HCL. In contrast, the results of the treatment of HCL-V with PNA
      are rather poor. There are also several reports indicating activity of PNAs in
      PLL and large granular lymphocyte leukemia. Clofarabine, nelarabine and
      forodesine need further investigation in rarer lymphid leukemias, to better
      define their status in the treatment of these disorders.

PMID- 22591388
TI  - Editorial: the importance of rational chemotherapy of chronic lymphocytic
      leukemia.

PMID- 22591389
TI  - The role of B cell receptor stimulation in CLL pathogenesis.
AB  - Chronic lymphocytic leukemia (CLL) is the most frequent leukemia in adults in the
      Western world and is characterized by the accumulation of monoclonal CD5(+)
      mature B cells in the blood. The disease has a highly variable clinical course.
      CLL is subdivided into two disease subtypes, whereby leukemias with hypermutated
      immunoglobulin heavy chain variable (IGHV) genes have a more favorable prognosis
      than those with unmutated IGHV genes, which tend to show advanced, progressive
      disease, adverse cytogenetic features and resistance to therapy. The current view
      is that both CLL types derive from antigen-experienced cells. Based on the
      finding that the IGHV repertoire is highly restricted and biased, as compared to
      the normal adult B-cell repertoire, it has been hypothesized that CLL cells are
      selected by some sort of antigenic pressure. Hereby, either autoantigens or
      antigens derived from apoptotic cells or pathogens are essential to trigger CLL
      pathogenesis. Although different cytogenetic aberrations were shown to contribute
      to CLL leukemogenesis, it remains unclear which abnormalities are primary events.
      Very recently, whole-genome sequencing identified genes that are recurrently
      mutated and provided novel insights into the mechanisms of oncogenic
      transformation. Because of the impact on prognosis, it is important to unravel
      the role of antigenic selection in CLL. Interestingly, B cell receptor (BCR)
      signaling is aberrantly increased in CLL and expression of tyrosine kinase ZAP70,
      which is able to signal downstream of the BCR, is a prognostic indicator. In this
      context we discuss the functional significance of antigenic selection in CLL and
      describe emerging agents to target BCR signaling that are currently being tested
      as a novel therapeutic strategy for CLL.

PMID- 22591390
TI  - Therapy of elderly/comorbid patients with chronic lymphocytic leukemia.
AB  - Treatment of chronic lymphocytic leukemia (CLL) has recently undergone
      revolutionary changes. Two large randomized trials demonstrated superiority of
      chemoimmunotherapy combining fludarabine and cyclophosphamide with monoclonal
      anti-CD20 antibody rituximab (FCR) over fludarabine and cyclophosphamide (FC)
      alone in first line and relapse; this lead to establishment of FCR regimen as new
      gold standard in younger and physically fit patients. However, elderly and/or
      comorbid patients may not tolerate such aggressive approach due to high risk of
      unacceptable toxicity. To date, no randomized trials in this patient population
      have improved therapeutic results over chlorambucil; therefore, this agent
      remains the backbone of treatment against which the new protocols should be
      tested. Indeed, several currently running large trials investigate whether
      addition of an anti-CD20 monoclonal antibody (rituximab, obinutuzumab,
      ofatumumab) to chlorambucil yields better results. Performance status, biological
      age and number/severity of comorbid conditions should be incorporated into
      decision-making process with regard to intensity of treatment. Other emerging
      treatment alternatives for this patient population include fludarabine-based
      regimens in attenuated doses as well as protocols containing bendamustine or
      lenalidomide. Highdose steroids combined with rituximab might be a promising in
      relapsed/refractory CLL but infectious toxicity is serious. Finally, ofatumumab
      has been recently approved for the treatment of fludarabine and alemtuzumab
      refractory patients. This article provides an overview of the current and future
      possibilities in the treatment of elderly and comorbid patients with CLL.

PMID- 22591391
TI  - Expression and activity of epithelial sodium channel in hyperoxia-induced
      bronchopulmonary dysplasia in neonatal rats.
AB  - BACKGROUND: The aim of the present study was to investigate the expression and
      activity of epithelial sodium channel (ENaC) in hyperoxia-induced
      bronchopulmonary dysplasia (BPD) in neonatal rats. METHODS: Neonatal rats were
      exposed to hyperoxia to establish BPD models (control group was exposed to air),
      lung water was measured and Western blot was applied to detect the expression of
      three homologous subunits: alpha-, beta- and gamma-ENaC in the lung tissues.
      Furthermore, ATII cells were isolated from neonatal rats, and primarily cultured
      under normoxic or hyperoxic conditions. The ENaC expression was also examined in
      these cells. In addition, the amiloride-sensitive Na(+) currents induced by
      hyperoxia were recorded using the whole-cell patch clamp technique. RESULTS: The
      alpha-ENaC expression was increased after 5 days of hyperoxia in rat lung
      tissues, whereas not after 1, 3 and 7 days. ATII cells showed alpha-ENaC
      expression was reduced after 1 and 2 days' hyperoxia, but no change after 3 days.
      In contrast, beta- and gamma-ENaC expression was increased after hyperoxia in
      both in vivo and in vitro experiments. The amiloride-sensitive Na(+) currents in
      hyperoxia-exposed ATII cells were also increased, which was consistent with the
      upregulated expression of beta- and gamma-ENaC. CONCLUSION: Hyperoxia upregulates
      the expression of ENaC, especially beta- and gamma-ENaC subunits, in both
      neonatal rat lung tissues and ATII cells. Hyperoxia also enhanced the activity of
      ENaC in neonatal rat ATII cells. Dysfunctional transport of Na(+) may not be a
      key factor involving pulmonary edema at the early stage of BPD.

PMID- 22591392
TI  - Nanoscale etching and flattening of metals with ozone water.
AB  - Etchants used for metal etching are generally harmful to the environment. We
      propose an environmentally friendly method that uses ozone water to etch metals.
      We measured the dependencies of ozone water etching on the temperature and ozone
      concentration for several metals and evaluated the surface roughness of the
      etched surfaces. The etching rate was proportional to the dissolved ozone
      concentration, and the temperature and the surfaces were smoothed by etching.

PMID- 22591393
TI  - Associations between chronotype and salivary endocrinological stress markers.
AB  - OBJECTIVES: To investigate the effect of chronotype on salivary cortisol or
      salivary alpha-amylase (sAA). METHODS: From 108 male university students, saliva
      samples were collected in the afternoon (between 15:00 and 17:00). The salivary
      cortisol and sAA levels were determined with commercial kits. Chronotype was
      quantitatively evaluated using the Horne and Ostberg Morningness-Eveningness
      Questionnaire. Subjects were categorized into morning types and evening types.
      RESULTS: The sAA levels were lower in the morning types than in the evening
      types. We found no significant difference in salivary cortisol levels between the
      two groups. CONCLUSIONS: These findings suggest that the sAA levels may be
      associated with chronotype.

PMID- 22591394
TI  - Structural effects and lipid membrane interactions of the pH-responsive GALA
      peptide with fatty acid acylation.
AB  - GALA is a pH-responsive, membrane-perturbing peptide designed to fold from a
      random coil at physiological pH to an amphipathic alpha-helix under mildly acidic
      conditions. Because of its pH-activated function, GALA has been sought-after as a
      component of intracellular drug delivery systems that could actively propel
      endosomal escape. In this study, we conjugated GALA with lauryl and palmitoyl
      fatty acid tails as model hydrophobic moieties and examined the physicochemical
      characteristics and activities of the resulting peptide amphiphiles (PAs). The
      fatty acid variants of GALA exhibited distinctly different membrane perturbing
      mechanisms at pH 7.5 and 5.5. At physiological pH, the PAs ruptured liposomes
      through a surfactant-like mechanism. At pH 5.5, lauryl-GALA was shown to form
      transmembrane pores with a higher potency as compared to its unmodified peptide
      counterpart; however, after prolonged exposure it also caused liposome lysis. The
      lytic activity of fatty acid-conjugated GALA did not impair cell viability.
      Lauryl-GALA was tolerated well by SJSA-1 osteocarcinoma cells and enhanced cell
      internalization of the PA was observed. Our findings are discussed with the
      overarching goal of developing efficient therapeutic delivery systems.

PMID- 22591395
TI  - Effects of fatigue on intermuscular common drive to the quadriceps femoris.
AB  - The purpose of this investigation was to examine intermuscular common drive to
      motor units in the vastus lateralis and vastus medialis during isometric
      contractions of the leg extensors. A secondary purpose was to investigate the
      effects of fatigue on the common drive. Fourteen healthy subjects (mean +/- SD,
      age = 21.7 +/- 1.5 years) volunteered to perform two separate isometric
      contractions of the leg extensors at 50% of the maximum voluntary contraction
      (MVC). These contractions were performed before (PRE) and immediately after
      (POST) a fatigue protocol of 10, 10 s isometric MVCs with 10 s of rest in between
      (i.e., 10 s on, 10 s off). During the PRE and POST isometric contractions,
      surface electromyographic (EMG) signals were detected from the vastus lateralis
      and vastus medialis and decomposed into individual motor unit action potential
      trains. A mean firing rate curve was then calculated for each motor unit, and the
      curves for the vastus lateralis were cross-correlated with those from the vastus
      medialis. The results showed that the average peak cross-correlation coefficients
      were always between 0.39 and 0.55, with coefficients for individual motor unit
      comparisons occasionally as high as 0.93. However, these coefficients were not
      affected by fatigue. These findings demonstrated a significant level of
      intermuscular common drive that was generally unaffected by fatigue.

PMID- 22591396
TI  - Exploring the effect of the Cardinium endosymbiont on spiders.
AB  - Spiders have recently emerged as important diversity hot spots for endosymbiotic
      bacteria, but the consequences of these symbiotic interactions are largely
      unknown. In this article, we examined the evolutionary history and effect of the
      intracellular bacterium Cardinium hertigii in the marbled cellar spider
      Holocnemus pluchei. We showed that Cardinium infection is primarily transmitted
      in spider populations maternally via egg cytoplasm, with 100% of the progeny from
      infected mothers being also infected. Examination of a co-inherited marker,
      mitochondrial DNA (mtDNA), revealed that Cardinium infection is associated with a
      wide diversity of mtDNA haplotypes, showing that the interaction between
      Cardinium and H. pluchei has a long-term evolutionary dimension and that
      horizontal transmission among individuals could also occur. Although Cardinium is
      well known to exert sex ratio distortion or cytoplasmic incompatibility in
      various arthropod hosts, we show, however, that Cardinium does not interact with
      the reproductive biology of H. pluchei. A field survey shows a clear geographical
      structuring of Cardinium infection, with a marked gradual variation of infection
      frequencies from ca. 0.80 to 0. We discuss different mechanistic and evolutionary
      explanations for these results as well as their consequences for spider
      phenotypes. Notably, we suggest that Cardinium can either behave as a neutral
      cytoplasmic element within H. pluchei or exhibit a context-dependent effect,
      depending on the environmental conditions.

PMID- 22591397
TI  - Speciation and frequency of virulence genes of Enterococcus spp. isolated from
      rainwater tank samples in Southeast Queensland, Australia.
AB  - In this study, 212 Enterococcus isolates from 23 rainwater tank samples in
      Southeast Queensland (SEQ), Australia were identified to the species level. The
      isolates were also tested for the presence of 6 virulence genes associated with
      Enterococcus related infections. Among the 23 rainwater tank samples, 20 (90%),
      10 (44%), 7 (30%), 5 (22%), 4 (17%), 2 (9%), and 1 (4%) samples yielded E.
      faecalis, E. mundtii, E. casseliflavus, E. faecium, E. hirae, E. avium, and E.
      durans, respectively. Among the 6 virulence genes tested, gelE and efaA were most
      prevalent, detected in 19 (83%) and 18 (78%) of 23 rainwater tank samples,
      respectively. Virulence gene ace was also detected in 14 (61%) rainwater tank
      samples followed by AS, esp (E. faecalis variant), and cylA genes which were
      detected in 3 (13%), 2 (9%), and 1 (4%) samples, respectively. In all, 120 (57%)
      Enterococcus isolates from 20 rainwater tank samples harbored virulence genes.
      Among these tank water samples, Enterococcus spp. from 5 (25%) samples harbored a
      single virulence gene and 15 (75%) samples were harboring two or more virulence
      genes. The significance of these strains in terms of health implications remains
      to be assessed. The potential sources of these strains need to be identified for
      the improved management of captured rainwater quality. Finally, it is recommended
      that Enterococcus spp. should be used as an additional fecal indicator bacterium
      in conjunction with E. coli for the microbiological assessment of rainwater
      tanks.

PMID- 22591398
TI  - Conductivity and spectroscopic investigation of
      bis(trifluoromethanesulfonyl)imide solution in ionic liquid 1-butyl-3
      methylimidazolium bis(trifluoromethanesulfonyl)imide.
AB  - Protic ionic liquids (PILs) are promising alternatives to water for swelling
      Nafion as a fuel cell proton exchange membrane (PEM). PILs can significantly
      improve the high-temperature performance of a PEM. The proton dissociation and
      solvation mechanisms in a PIL, which are keys to understanding the proton
      transportation and conductivity, have not been fully explored. In this paper, we
      used FTIR, Raman, and electronic spectroscopy with computational simulation
      techniques to explore the spectroscopic properties of
      bis(trifluoromethanesulfonyl)imide (HTFSI) solutions in 1-butyl-3
      methylimidazolium bis(trifluoromethanesulfonyl)imide (BMITFSI) ionic liquid at
      concentrations from ~0.1 to as high as ~1.0 M. Solution conductivities were
      measured at room temperature and elevated temperatures up to ~65  degrees C. The
      solution structure and properties depend on the concentration of HTFSI. At lower
      concentration, around 0.1 M, the HTFSI solution has higher conductivity than pure
      BMITFSI. However, the conductivity decreases when the concentration increases
      from 0.1 to 1.0 M. Temperature-dependent conductivities followed the Vogel
      Fulcher-Tamman equation at all concentrations. Conductivity and spectroscopy
      results elucidate the complicated ionization and solvation mechanism of HTFSI in
      BMITFSI solutions. Raman spectroscopy and density functional theory (DFT)
      calculations are consistent with the complete ionization of HTFSI to generate
      solvated H(+) at low concentrations. FTIR, Raman, and electronic spectroscopic
      results as well as DFT computational simulation indicated that when the
      concentration is as high as 1.0 M, a significant amount of TFSI(-) is protonated,
      most likely at the imide nitrogen.

PMID- 22591399
TI  - Involvement of metabotropic glutamate receptor 5 signaling in activity-related
      proliferation of adult hippocampal neural stem cells.
AB  - Adult hippocampal neural stem cells can be activated by hippocampal neural
      activities. When focal cerebral ischemia, known as middle cerebral artery
      occlusion (MCAO), occurs, neural stem cells are activated to promote their
      proliferation. However, the mechanism by which these cells are activated is still
      unclear. Here, we indicate the involvement of metabotropic glutamate receptor 5
      (mGluR5) signaling in neural stem cells in their activity-related proliferation
      after MCAO. We found mGluR5 molecules on neural stem cells by using calcium
      imaging. We detected the activation of neural stem cells by adding the mGluR5
      agonist (RS)-2-chloro-5-hydroxyphenylglycine. On a hippocampal slice, the
      activation of neural stem cells to promote their proliferation was initiated by
      theta-burst electrical stimulation at the perforant pathway, and this activation
      was significantly blocked by an mGluR5 antagonist, 2-methyl-6
      (phenylethynyl)pyridine (MPEP). In addition to this, the injection of the blood
      brain barrier-permeable mGluR5 agonist 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5
      yl)benzamide into live mice promoted the proliferation of neural stem cells.
      Moreover, in vivo theta-burst electrical stimulation induced proliferation of
      neural stem cells. A chronic field recording study showed that the activity of
      the hippocampal formation was elevated after MCAO. Finally, we observed that the
      mGluR5 antagonist MPEP significantly blocked the stimulated proliferation of
      neural stem cells induced by MCAO, by blocking mGluR5 signaling. Our results
      suggest that glutamates released by the elevated neural activities after MCAO may
      trigger mGluR5 signaling in neural stem cells to promote their proliferation.

PMID- 22591401
TI  - Impaired degradation followed by enhanced recycling of epidermal growth factor
      receptor caused by hypo-phosphorylation of tyrosine 1045 in RBE cells.
AB  - BACKGROUND: Since cholangiocarcinoma has a poor prognosis, several epidermal
      growth factor receptor (EGFR)-targeted therapies with antibody or small molecule
      inhibitor treatment have been proposed. However, their effect remains limited.
      The present study sought to understand the molecular genetic characteristics of
      cholangiocarcinoma related to EGFR, with emphasis on its degradation and
      recycling. METHODS: We evaluated EGFR expression and colocalization by
      immunoblotting and immunofluorescence, cell surface EGFR expression by
      fluorescence-activated cell sorting (FACS), and EGFR ubiquitination and protein
      binding by immunoprecipitation in the human cholangiocarcinoma RBE and
      immortalized cholangiocyte MMNK-1 cell lines. Monensin treatment and Rab11a
      depletion by siRNA were adopted for inhibition of EGFR recycling. RESULTS: Upon
      stimulation with EGF, ligand-induced EGFR degradation was impaired and the
      expression of phospho-tyrosine 1068 and phospho-p44/42 MAPK was sustained in RBE
      cells as compared with MMNK-1 cells. In RBE cells, the process of EGFR sorting
      for lysosomal degradation was blocked at the early endosome stage, and non
      degradated EGFR was recycled to the cell surface. A disrupted association between
      EGFR and the E3 ubiquitin ligase c-Cbl, as well as hypo-phosphorylation of EGFR
      at tyrosine 1045 (Tyr1045), were also observed in RBE cells. CONCLUSION: In RBE
      cells, up-regulation of EGFR Tyr1045 phosphorylation is a potentially useful
      molecular alteration in EGFR-targeted therapy. The combination of molecular
      targeted therapy determined by the characteristics of individual EGFR
      phosphorylation events and EGFR recycling inhibition show promise in future
      treatments of cholangiocarcinoma.

PMID- 22591402
TI  - Identification of imidazo-pyrrolopyridines as novel and potent JAK1 inhibitors.
AB  - A therapeutic rationale is proposed for the treatment of inflammatory diseases,
      such as rheumatoid arthritis (RA), by specific targeting of the JAK1 pathway.
      Examination of the preferred binding conformation of clinically effective, pan
      JAK inhibitor 1 led to identification of a novel, tricyclic hinge binding
      scaffold 3. Exploration of SAR through a series of cycloamino and cycloalkylamino
      analogues demonstrated this template to be highly tolerant of substitution, with
      a predisposition to moderate selectivity for the JAK1 isoform over JAK2. This
      study culminated in the identification of subnanomolar JAK1 inhibitors such as 22
      and 49, having excellent cell potency, good rat pharmacokinetic characteristics,
      and excellent kinase selectivity. Determination of the binding modes of the
      series in JAK1 and JAK2 by X-ray crystallography supported the design of
      analogues to enhance affinity and selectivity.

PMID- 22591403
TI  - A quantitative metric for pattern fidelity of bioprinted cocultures.
AB  - This article describes a quantitative metric for coculture pattern fidelity and
      its use in the assessment of bioprinting systems. Increasingly, bioprinting is
      used to create in vitro cell and tissue models for the purpose of studying cell
      behavior and cell-cell interaction. To create meaningful models, a bioprinting
      system must be able to place cells in biologically relevant patterns with
      sufficient fidelity. A metric for assessing fidelity would be valuable for tuning
      experimental processes and parameters within a bioprinting system and for
      comparing performance between different systems. Toward this end, the
      "bioprinting fidelity index" (BFI), a metric which rates a bioprinted patterned
      coculture with a single number based on the proportions of correctly placed
      cells, is proposed. Additionally, a mathematical model of drop-on-demand printing
      is introduced, which predicts an upper bound on the BFI based on drop placement
      statistics. A proof-of-concept study was conducted in which patterned cocultures
      of D1 and 4T07 cells were produced in two different demonstration patterns. The
      BFI for the patterned cocultures was calculated and compared to the printing
      model fidelity prediction. The printing model successfully predicted the best BFI
      observed in the samples, and the BFI showed quantitatively that post-processing
      techniques negatively impacted the final fidelity of the samples. The BFI
      provides a principled method for comparing printing and post-processing methods.

PMID- 22591404
TI  - Conjugated linoleic acid conversion by six Lactobacillus plantarum strains
      cultured in MRS broth supplemented with sunflower oil and soymilk.
AB  - Six strains of Lactobacillus plantarum, isolated from traditional dairy products
      of minority nationalities, were evaluated for their ability to produce conjugated
      linoleic acid (CLA) from free linoleic acid in vitro. All the 6 strains were
      found to be capable of converting linoleic acid to CLA when using sunflower oil
      as substrate or during soymilk fermentation. The inhibitory effect of linoleic
      acid on the growth of the L. plantarum was also discussed. The production of CLA
      was increased with adding high concentration of substrate in sunflower oil and
      IMAU60042 produced the highest CLA both in sunflower oil and soymilk. The CLA was
      composted by 2 isomers: cis9, trans11-CLA and tran10, cis12-CLA, and cis9, tran
      s11-CLA covered the most part of the total CLA formed except for L. plantarum P8.
      The production of CLA was decreased during the storage of fermented soymilk. The
      CLA contents decreased significantly in the first week, also more quickly in 2
      wk. Especially, tran10, cis12-CLA decreased more rapidly than cis9, tran11-CLA.
      No dramatic change was observed among other 8 fatty acids in soymilk. The
      proportion of unsaturated fatty acids varied after fermentation with different L.
      plantrum strains, but all decreased the during storage. The research on the
      ability of converting CLA of L. plantrum strains could be basis for the future
      research and development of fermented soymilk products. PRACTICAL APPLICATION:
      Desirable probiotic traits, such as acid and bile tolerance, aggregation
      activity, and antibacterial activity, have been proved for the 6 Lactobacillus
      plantarum strains. The 6 L. plantarum strains might be used in the fermentation
      of soymilk to produce multifunctional probiotic soymilk products, especially the
      rich CLA contents.

PMID- 22591405
TI  - Is vitamin D beneficial to Alzheimer disease? A surprising dilemma.

PMID- 22591406
TI  - Endoscopic observations of blocked ventriculoperitoneal (VP) shunt: a step toward
      better understanding of shunt obstruction and its removal.
AB  - OBJECTIVES: Most of our understanding of ventriculoperitoneal (VP) shunt blockage
      (ventricular end) is based on in vitro studies of blocked VP shunts. Not much
      information is available regarding the in vivo changes that occur in the tube and
      in the surrounding ventricle. The primary aim of our study was to observe and
      analyse these changes, directly, through the endoscope, in patients with blocked
      shunts undergoing an endoscopic third ventriculostomy (ETV). Based on these
      findings, we have also suggested criteria for safe removal of the VP shunt tube
      following ETV. MATERIAL AND METHODS: ETV was performed with standard technique in
      patients with blocked VP shunt. The ventricular end of the shunt tube was
      inspected through the endoscope, for changes in ventricle linings as well as in
      the shunt tube. These changes were correlated with the age of the patient,
      etiology of HC, type or make of the shunt tube, duration of shunt placement to
      ETV and the CSF findings. RESULTS: Fifty-three patients of blocked VP shunt
      underwent ETV from July 2006 to April 2010. Thirty patients had Chhabra (CH) V P
      Shunt (Surgiwear, India) and 23 had ceredrain (CD) shunt (Hindustan Latex,
      India). The age of the patients ranged from 2 months to 60 years (mean--13.33
      years.). Various causes of hydrocephalus (HC) included congenital hydrocephalus
      (aqueductal stenosis) in 18 patients, post-meningitis hydrocephalus (PMH) in 32
      cases, neuro-cysticercosis (NCC) in 2 patients and intraventricular haemorrhagic
      (IVH) in 1 patient. Clinical and radiological improvement occurred in 33
      (62.21%), and 24 (45%) patients, respectively. Freedom from shunt was attained in
      20 (38%) patients. The changes around the shunt tube were seen in 41 (77%).
      Hyperaemia and neovascularised ependyma was seen in 20 (37%) and 15 (28%)
      patients. Encasement of the tube was seen in 41%. Ependymal growth and
      neovascularised shunt tubes were noticed in 15% each. Choroid plexus blocking the
      tube was seen in only four cases (7%). VP shunt was revised in 14 patients
      (26.4%). Patient with infective etiology had more changes (p < 0.005). Age, CSF
      findings and make of shunt tube had no relation with endoscopic observations (p<
      0.02). CONCLUSIONS: ETV has a role in shunt failures. It can offer patient a
      chance of shunt free life. Endoscopic observation of shunt tube and ventricle can
      unfold several interesting in vivo findings pertaining to shunt obstruction.
      Shunt should only be removed if there are no adhesions and neovascularisation.

PMID- 22591407
TI  - A novel mutation in the beta-tubulin gene TUBB2B associated with complex
      malformation of cortical development and deficits in axonal guidance.
AB  - Neurological disorders characterized by abnormal neuronal migration,
      organization, axon guidance, and maintenance have recently been associated with
      missense and splice-site mutations in the genes encoding alpha- and beta-tubulin
      isotypes TUBA1A, TUBB2B, TUBB3, and TUBA8. We found a novel heterozygous mutation
      c.419G > C in exon 4 of the gene encoding TUBB2B in a female with microcephaly,
      agenesis of the corpus callosum, open-lip schizencephaly of the left parietal
      lobe, extensive polymicrogyria, basal ganglia and thalami dysmorphisms, and
      vermis and right third nerve hypoplasia. The missense change results in a glycine
      to alanine substitution; the mutated residue falls within an invariant glycine
      rich region and therefore is likely to result in impaired protein function and
      possibly microtubule formation. This study expands the spectrum of brain
      malformations associated with mutations in the beta-tubulin gene TUBB2B,
      supporting its critical role in migration/organization and axon guidance
      processes. In addition, it suggests a possible genetic aetiology of
      schizencephaly, thus strengthening the hypothesis that there is a common
      pathophysiological base in polymicrogyria and schizencephaly.

PMID- 22591408
TI  - Health-related quality of life and cost-effectiveness of treatment in
      subarachnoid haemorrhage.
AB  - BACKGROUND: Treatment of aneurysmal subarachnoid haemorrhage (SAH) demands high
      healthcare resource utilization. Case fatality and disability remain as common
      outcomes of SAH. The purpose of this study was to perform a treatment cost
      effectiveness analysis of patients with SAH. METHODS: We performed a long-term
      follow-up of the SAH patients treated in our institution over a 3-year period
      starting February 1998. Outcome 10 years after the SAH and treatment costs were
      evaluated. The health-related quality of life was evaluated using the EuroQol (EQ
      5D) questionnaire and visual-analogue scale (VAS). The cost of a quality-adjusted
      life year (QALY) was calculated. RESULTS: Median follow-up time of the 178
      patients was 10.8 years. Overall mortality rate was 24%. Of the 43 non-survivors,
      42% died within 6 months. For the 135 survivors, the median EQ-5D index value was
      1.00, which is similar to that for normal population. The median VAS value was
      80, which is comparable to normal population's value. Of the survivors, 88%
      (119/135) were able to live at home and 63% (85/135) returned to work after SAH.
      The cost of neurosurgical treatment for one QALY was 1700?. CONCLUSION: Long-term
      outcome of survivors after aneurysmal SAH was relatively good: most of them lived
      at home, 63% had returned to work and 36% were still working. The quality of life
      index of the survivors was similar to that of normal populations, and the
      survivors were as satisfied with their health as people in general are. Cost of
      neurosurgical treatment and cost of a QALY gained were acceptable.

PMID- 22591410
TI  - Universal temperature crossover behavior of electrical conductance in a single
      oligothiophene molecular wire.
AB  - We have observed and analyzed a universal temperature crossover behavior of
      electrical conductance in a single oligothiophene molecular wire. The crossover
      between the Arrhenius-type temperature dependence at high temperature and the
      temperature-invariant behavior at low temperature is found at a critical
      molecular wire length of 5.6 nm, where we found a change from the exponential
      length dependence to the length-invariant behavior. We have derived a scaling
      function analysis for the origin of the crossover behavior. After assuring that
      the analysis fits the explanation of the Keldysh Green's function calculation for
      the temperature dependence, we have applied it to our experimental results and
      found successfully that our scaling function gives a universal description of the
      temperature dependence for all over the temperature range.

PMID- 22591409
TI  - Chronic immobilization in the malpar1 knockout mice increases oxidative stress in
      the hippocampus.
AB  - The lysophosphatidic acid LPA1 receptor has recently been involved in the
      adaptation of the hippocampus to chronic stress. The absence of LPA1 receptor
      aggravates the chronic stress-induced impairment of both hippocampal neurogenesis
      and apoptosis that were accompanied with hippocampus-dependent memory deficits.
      Apoptotic death and neurogenesis in the hippocampus are regulated by oxidative
      stress. In the present work, we studied the involvement of LPA1 receptor
      signaling pathway in the regulation of the hippocampal redox after chronic
      stress. To this end, we used malpar1 knockout (KO) and wild-type mice assigned to
      either chronic stress (21 days of restraint, 3 h/day) or control conditions.
      Lipid peroxidation, the activity of the antioxidant enzymes catalase (CAT),
      superoxide dismutase (SOD), and glutathione peroxidase (GPX), as well as
      mitochondrial function stimulation, monitored through the activity of cytochrome
      c oxidase (COX), were studied in the hippocampus. Our results showed that chronic
      immobilization stress enhanced lipid peroxidation as well as the activity of the
      antioxidant enzymes studied (CAT, SOD, and GPX). This effect was only observed in
      absence of LPA1 receptor. Furthermore, only malpar1 KO mice submitted to chronic
      stress exhibited a severe downregulation of the COX activity, suggesting the
      presence of mitochondrial damage. Altogether, these results suggest that malpar1
      KO mice display enhanced oxidative stress in the hippocampus after chronic
      stress. This may be involved in the hippocampal abnormalities observed in this
      genotype after chronic immobilization, including memory, neurogenesis, and
      apoptosis.

PMID- 22591411
TI  - Acoustic phonon lifetimes and thermal transport in free-standing and strained
      graphene.
AB  - We use first-principles methods based on density functional perturbation theory
      to characterize the lifetimes of the acoustic phonon modes and their consequences
      on the thermal transport properties of graphene. We show that using a standard
      perturbative approach, the transverse and longitudinal acoustic phonons in free
      standing graphene display finite lifetimes in the long-wavelength limit, making
      them ill-defined as elementary excitations in samples of dimensions larger than
      ~1 MUm. This behavior is entirely due to the presence of the quadratic
      dispersions for the out-of-plane phonon (ZA) flexural modes that appear in free
      standing low-dimensional systems. Mechanical strain lifts this anomaly, and all
      phonons remain well-defined at any wavelength. Thermal transport is dominated by
      ZA modes, and the thermal conductivity is predicted to diverge with system size
      for any amount of strain. These findings highlight strain and sample size as key
      parameters in characterizing or engineering heat transport in graphene.

PMID- 22591412
TI  - Formation of substrate-supported membranes from mixtures of long- and short-chain
      phospholipids.
AB  - We studied the formation of substrate-supported planar phospholipid bilayers
      (SPBs) on glass and silica from mixtures of long- and short-chain phospholipids
      to assess the effects of detergent additives on SPB formation. 1,2-Hexyanoyl-sn
      glycero-3-phosphocholine (DHPC-C6) and 1,2-heptanoyl-sn-glycero-3-phosphocholine
      (DHPC-C7) were chosen as short-chain phospholipids. 1-Palmitoyl-2-oleol-sn
      glycero-3-phosphocholine (POPC) was used as a model long-chain phospholipid.
      Kinetic studies by quartz crystal microbalance with dissipation monitoring (QCM
      D) showed that the presence of short-chain phospholipids significantly
      accelerated the formation of SPBs. Rapid rinsing with a buffer solution did not
      change the adsorbed mass on the surface if POPC/DHPC-C6 mixtures were used below
      the critical micelle concentration (cmc) of DHPC-C6, indicating that an SPB
      composed of POPC molecules remained on the surface. Fluorescence microscopy
      observation showed homogeneous SPBs, and the fluorescence recovery after
      photobleaching (FRAP) measurements gave a diffusion coefficient comparable to
      that for SPBs formed from POPC vesicles. However, mixtures of POPC/DHPC-C7
      resulted in a smaller mass of lipid adsorption on the substrate. FRAP
      measurements also yielded significantly smaller diffusion coefficients,
      suggesting the presence of defects. The different behaviors for DHPC-C6 and DHPC
      C7 point to the dual roles of detergents to enhance the formation of SPBs and to
      destabilize them, depending on their structures and aggregation properties.

PMID- 22591413
TI  - Time-resolved studies of charge recombination in the pyrene/TCNQ charge-transfer
      crystal: evidence for tunneling.
AB  - Previous studies of solid-state tetracyanobenzene-based donor-acceptor complexes
      showed that these materials were highly susceptible to both laser and mechanical
      damage that complicated the analysis of their electron-transfer kinetics. In this
      paper, we characterize the optical properties of a
      pyrene/tetracyanoquinodimethane charge-transfer crystal that is much more robust
      than the tetracyanobenzene compounds. This donor-acceptor complex has a charge
      transfer absorption that extends into the near-infrared, rendering the crystal
      black. We use time-resolved fluorescence and diffuse reflectance transient
      absorption to study its dynamics after photoexcitation. We show that the
      initially excited charge-transfer state undergoes a rapid, monoexponential decay
      with a lifetime of 290 ps at room temperature. There is no evidence for any long
      lived intermediate or dark states; therefore, this decay is attributed to charge
      recombination back to the ground state. Fluorescence lifetime measurements
      demonstrate that this process becomes temperature-independent below 60 K,
      indicative of a thermally activated tunneling mechanism. The subnanosecond charge
      recombination makes this low-band-gap donor-acceptor material a poor candidate
      for generating long-lived electron-hole pairs.

PMID- 22591414
TI  - Non-HPLC rapid separation of metallofullerenes and empty cages with TiCl4 Lewis
      acid.
AB  - Rapid and efficient separation/purification of pure metallofullerenes M(x)@C(n)
      (M = metal; x = 1, 2; n > 70) and carbide metallofullerenes of the type
      M(y)C(2)@C(n-2) (y = 2, 3, 4; n - 2 > 68) has been reported. The present method
      utilizes rapid and almost perfect preferential formation of TiCl(4) (generally
      known as a Lewis acid)-metallofullerene complexes, which easily decompose to
      provide pure metallofullerene powders by a simple water treatment. The present
      method enables one to separate the metallofullerenes up to >99% purity within 10
      min without using any type of high-performance liquid chromatography (HPLC). It
      is found that the oxidation potentials of the metallofullerenes are crucial
      factors for efficient purification. The current separation/purification technique
      may open a brand-new era for inducing further applications and commercialization
      of endohedral metallofullerenes.

PMID- 22591416
TI  - Two unrelated items to avoid, one for me and one for you.

PMID- 22591415
TI  - Impact on wound healing and efficacy of various leg ulcer debridement techniques.
AB  - AIM: To evaluate the evidence on the impact of different debridement techniques
      on healing and their efficacy in the treatment of leg ulcers. METHODS: Web-based
      search (PubMed) for trials investigating surgical, enzymatic, autolytic, osmotic,
      ultrasound-assisted, and biosurgical wound debridement on leg ulcers with regard
      to healing and efficacy. RESULTS: Both surgical and hydrosurgical methods proved
      to be effective debridement techniques. For conventional surgical debridement, a
      significantly greater reduction of the wound surface area and a higher healing
      rate were reported. Studies on autolytic, osmotic, and enzymatic wound
      debridement showed effective debridement for krill enzymes, dextranomer and
      manuka honey. Only for manuka honey was there a significantly greater reduction
      of the wound surface area compared to standard treatment. One study comparing
      fibrinolysin/DNAse with placebo and one comparing autolytic with enzymatic
      debridement showed no significant differences between the respective techniques.
      Trials on ultrasound-assisted wound debridement reported a positive impact on
      healing. A significant wound surface area reduction was demonstrated in one of
      them. Maggot therapy led to effective debridement. The largest trial showed no
      significantly improved healing. CONCLUSIONS: Further studies are needed to
      strengthen the evidence for a significant impact of wound debridement on the
      healing of leg ulcers.

PMID- 22591417
TI  - Review of dose-intense platinum and/or paclitaxel containing chemotherapy in
      advanced and recurrent epithelial ovarian cancer.
AB  - Ovarian cancer is the most lethal gynecological cancer in women in the western
      world with a 5-year survival of 49.7%. Advanced stage ovarian cancer is treated
      both surgically and with chemotherapy, but despite initial high response rates of
      60- 75%, many women experience disease recurrence with a dismal prognosis, 5 year
      overall survival for FIGO stage IIIc and IV disease being only 32 and 18%. In an
      attempt to improve outcome for both primary and recurrent disease, dose-intense
      and dose-dense chemotherapy regimens have been investigated. This overview
      summarizes these results in first and second-line treatment. In first-line
      treatment, no benefit was found of dose-intense regimes in the majority of the
      studies, only toxicity was increased. However, results are conflicting with the
      recent Japanese Gynecologic Oncology Group (JGOG) trial showing an improved
      progression free and overall survival in patients treated with dose-dense weekly
      paclitaxel combined with standard 3-weekly carboplatin. For recurrent disease
      dose-dense weekly combination chemotherapy seems to be very effective in patients
      with platinum-resistant ovarian cancer. Several phase II studies showed an
      increase in response rate, progression free survival and overall survival for
      dose-dense paclitaxel and carboplatin, compared to results of nonplatinum
      chemotherapy. In platinum-sensitive ovarian cancer, on contrary, the results of
      weekly paclitaxel and carboplatin seem to be comparable with standard 3-weekly
      regimens.

PMID- 22591418
TI  - Interleukin-6/interleukin-6 receptor pathway as a new therapy target in
      epithelial ovarian cancer.
AB  - Epithelial ovarian cancer is a major problem as about 75% of patients develop
      recurrence after initial primary treatment and tumors are often chemoresistant.
      This article reviews the role of the interleukin-6 (IL-6) in chemoresistance and
      suppression of tumor immunity in ovarian cancer and provides the rationale for
      modulating the IL-6/ IL-6 receptor (IL-6R) induced pathway as a potential new
      target for the treatment of ovarian cancer. IL-6 is elevated in serum and ascites
      of ovarian cancer patients and increased IL-6 levels correlate with
      chemoresistance and poor prognosis in these patients. IL-6 induced Jak/Stat3,
      Ras/MEK/ERK and PI3K/Ras signaling pathways lead to cell survival, proliferation,
      angiogenesis, and confers resistance to apoptosis induced by conventional
      therapies. Furthermore, IL-6 induces tumor-promoting macrophages which are known
      to foster tumor growth and suppress local immunity. However, direct proof of the
      clinical impact of IL-6 blocking on disease progression is missing necessiting
      further studies in which the IL-6(R) pathway is modulated and its clinical impact
      on (epithelial) ovarian cancer is tested.

PMID- 22591419
TI  - Role of farletuzumab in epithelial ovarian carcinoma.
AB  - Epithelial ovarian cancer (EOC) is the most lethal of the gynecologic
      malignancies, largely due to the advanced stage at diagnosis in most patients.
      Standard treatment for EOC is surgical debulking followed by platinum-based
      chemotherapy. While the majority of ovarian cancer patients will respond to
      initial chemotherapy, most will ultimately relapse. The major focus of current
      clinical trials for treatment of recurrent ovarian cancer is the use of targeted
      biologic agents. Folate receptor alpha (FRalpha) is upregulated in majority of
      EOC and correlated with tumor stage and grade. It is hypothesized that the
      presence of overexpressed FRalpha correlates with the propagation rate of the
      tumors. FRalpha is largely absent from normal tissue, making it an attractive
      therapeutic target. Farletuzumab (MORAb-003), a humanized monoclonal antibody
      against FRalpha, has shown antitumor activity in preclinical xenograft models. A
      Phase 1 dose escalation study did not demonstrate dose-limiting toxicities, or
      severe adverse effects. A phase 2 efficacy and safety study of farletuzumab with
      carboplatin and taxane in patients with platinum-sensitive EOC in first relapse,
      have shown an improved response rate and time to progression compared with
      historical controls. Recently, preliminary safety data from a phase 1 trial
      reported that the combination of farletuzumab, carboplatin and PLD has an
      acceptable safety profile in patients with platinum- sensitive EOC following
      first or second relapse. Two randomized, double-blind, placebo-controlled Phase 3
      studies with farletuzumab plus chemotherapy have been done. A trial of:
      farletuzumab with weekly paclitaxel in platinum-resistant EOC closed in December
      2011 with full report pending. A second trial of farletuzumab with carboplatin
      and taxane in platinum-sensitive EOC in first relapse is slated to complete
      accrual in early 2012. Results from these trials will help define the role of
      farletuzumab in EOC.

PMID- 22591420
TI  - The role of bevacizumab in advanced epithelial ovarian cancer.
AB  - BACKGROUND: There is a strong rationale for usage of anti-angiogenic agents in
      epithelial ovarian cancer. Bevacizumab is the most widely investigated anti-VEGF
      agent and has shown promising results in recent clinical trials. OBJECTIVE: To
      review the rationale and usage of bevacizumab in advanced epithelial ovarian
      cancer; as mono-therapy, in combination with chemotherapy both as first line and
      for recurrent ovarian cancer as well as in combination with other targeted
      therapies. RESULTS: In epithelial ovarian cancer, angiogenesis promotes tumor
      growth, ascites formation and metastasis. Targeting VEGF in ovarian cancer
      patients may have indirect and direct cytotoxic effects. Results of placebo
      controlled phase III trials, the GOG-218 and ICON7, of carboplatin-paclitaxel
      alone or combined with bevacizumab in chemo-naive patients and the OCEAN trial
      comparing carboplatin-gemcitabine with or without bevacizumab in women with
      recurrent platinum-sensitive epithelial ovarian cancer all suggest a benefit for
      the addition of bevacizumab on progression free survival. Additionally,
      bevacizumab in combination with other targeted therapies, such as sorafenib and
      everolimus are under investigation in phase II trials and the current knowledge
      of molecular predictors is discussed. IN CONCLUSION: Until now no survival
      benefit has been observed, but bevacizumab is the first anti-angiogenic agent
      demonstrating a progression free survival benefit in addition to standard
      chemotherapy regimens in advanced epithelial ovarian cancer, both in the upfront
      and recurrent setting. Mature overall survival data and the search for predictive
      biomarkers are important for the future role of bevacizumab in epithelial ovarian
      cancer.

PMID- 22591421
TI  - Trabectedin as a new chemotherapy option in the treatment of relapsed platinum
      sensitive ovarian cancer.
AB  - Trabectedin (ET-743, Yondelis(r)) is a novel marine antineoplastic alkaloid with
      a unique mechanism of action. The active substance trabectedin, a
      tetrahydroisoquinoline alkaloid, is a natural product originally isolated from
      the Caribbean sea squirt, Ecteinascidia turbinata and is currently manufactured
      by total synthesis. Trabectedin is licensed by the Spanish pharmaceutical drug
      company, PharmaMar and co-developed by Johnson & Johnson Pharmaceutical Research
      and Development, L.L.C., pursuant to a licensing agreement with PharmaMar.
      Trabectedin is the first anticancer marine-derived drug to be approved by the
      European Union. In 2007, trabectedin obtained marketing authorization from the
      European Commission and in many other countries worldwide for the treatment of
      patients with advanced soft tissue sarcoma (STS) after failure of anthracyclines
      and ifosfamide, or for those patients who are unsuitable to receive these agents.
      Based on the recently reported results of a large phase III study (OVA-301)
      comparing pegylated liposomal doxorubicin (PLD) alone with a combination of PLD
      and trabectedin in patients with recurrent ovarian cancer, in 2009 the European
      Commission granted marketing authorization for trabectedin combined with PLD for
      the treatment of patients with relapsed platinum-sensitive ovarian cancer. The
      results from OVA-301 showed that the combination of trabectedin and PLD improves
      progression-free survival and overall response rate over PLD alone with
      acceptable tolerance in the second-line treatment of recurrent ovarian cancer. In
      addition, an enhanced activity of trabectedin combined with PLD was observed in
      platinum sensitive patients, especially in those with a platinum-free interval
      ranging from 6 to 12 months. Overall, trabectedin-induced toxicities are mainly
      hematological and hepatic, with grade 3/4 neutropenia and thrombocytopenia
      observed in approximately 50% and 13% of patients, respectively, and grade 3/4
      elevation of liver aminotransferases observed in 40-50% of patients treated with
      trabectedin. Current efforts are focused on the evaluation of the role of
      trabectedin in prolonging the platinum-free interval and the identification of
      predictive factors for patients treated with trabectedin as well as in the
      development of new trabectedin-based combinations.

PMID- 22591422
TI  - Survival benefit of adding Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) at
      the different time-points of treatment of ovarian cancer: review of evidence.
AB  - The standard treatment for advanced ovarian cancer consists in complete
      cytoreductive surgery (CRS) and intravenous combination chemotherapy with a
      platinum compound and a taxane. Although response rates to initial therapy are
      high, many patients will recur and die of peritoneal carcinomatosis. The addition
      of Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) to the standard therapy aims
      at increasing survival by reducing peritoneal recurrence. This review describes
      the survival results of HIPEC at the different time-points of the treatment of
      ovarian cancer: at upfront CRS, at interval CRS, at consolidation CRS after
      complete response to initial therapy, at secondary CRS after incomplete response,
      at salvage CRS for recurrence and as palliative treatment without CRS for
      unresectable ovarian cancer with chemotherapy resistant ascites. The available
      evidence suggests that a potential survival benefit of adding HIPEC may be
      largest in the settings of secondary CRS for stage III ovarian cancer and salvage
      CRS for recurrent ovarian cancer, two time-points representing failure of initial
      standard therapy. There is much less evidence for a potential benefit of HIPEC
      for less advanced stages (I-II) and for earlier time-points in the treatment of
      ovarian cancer (upfront, interval and consolidation). Postoperative mortality is
      not higher after CRS and HIPEC (0.7%) than after CRS only (1.4%). Four randomised
      trials are ongoing and their results are eagerly awaited. Palliative HIPEC
      without CRS might be used more in patients with incapacitating ascites due to
      recurrent ovarian cancer which has become resistant to systemic chemotherapy.

PMID- 22591423
TI  - The role of PARP inhibitors in the treatment of ovarian carcinomas.
AB  - Homologous recombination (HR), a key mechanism of DNA double strand break (DSB)
      repair, is commonly defective in high grade serous carcinomas (HGSC) of the
      ovary. BRCA1/2 mutations, as well as many other molecular and genetic defects,
      can lead to impaired HR. Treatment of HR-defective tumours with poly-ADP ribose
      polymerase (PARP) inhibitors, which block the key mechanism of single strand DNA
      breaks (SSB), exploits a therapeutic concept called "synthetic lethality". Early
      experiences with PARP inhibitors in germline BRCA mutation carriers and sporadic
      HGSCs of the ovary have been promising. The development of PARP inhibitors for
      ovarian cancer is an area of active research. This article provides an overview
      of the molecular rationale for the use of PARP inhibitors and summarizes some of
      the key early clinical data of their use in ovarian cancer.

PMID- 22591424
TI  - Multiple VEGF family members are simultaneously expressed in ovarian cancer: a
      proposed model for bevacizumab resistance.
AB  - OBJECTIVE: Insight into the expression of multiple vascular endothelial growth
      factor (VEGF) family members can support the implementation of anti-angiogenic
      therapy. This study aimed to assess VEGF family member expression in ovarian
      cancers and related omental metastases. METHODS: Tissue microarrays encompassing
      270 primary cancers and 112 paired metastases were immunostained for VEGF-A, VEGF
      B, VEGF-C and VEGF-D. Staining intensities were categorized as absent, weak,
      moderate or strong. Expression was related to clinicopathological characteristics
      and survival. RESULTS: Immunohistochemical positivity (defined as moderate or
      strong expression) was observed for VEGF-A in 90%, VEGF-B in 4%, VEGF-C in 41%
      and VEGF-D in 55% of the primary ovarian cancers. VEGF-A expression correlated
      with VEGF-C and VEGF-D expression (P < 0.01). Simultaneous positivity for VEGF-A
      and VEGF-C or VEGF-D was observed in 38% and 54% of the cancers, respectively.
      Metastases showed positivity for VEGF-A in 78%, VEGF-B in 5%, VEGF-C in 26% and
      VEGF-D in 45% of cases. VEGF family member expression showed no independent
      prognostic significance in multivariate survival analysis. CONCLUSION: VEGF-A,
      VEGF-C and VEGF-D are widely and often simultaneously expressed in ovarian
      cancer, which may contribute to bevacizumab resistance. Measuring their
      expression could support a rational, individualized choice of anti-angiogenic
      therapy and might be of predictive value. Studies are warranted to determine
      whether combinatorial analysis of VEGF family member expression can be used to
      predict anti-angiogenic drug efficacy.

PMID- 22591425
TI  - Antigen-specific immunotherapy in ovarian cancer and p53 as tumor antigen.
AB  - Immunotherapy for ovarian cancer is one of the new treatment strategies currently
      investigated in epithelial ovarian cancer. This review discusses the results of
      different immunization strategies, identifies possible drawbacks in study design
      and provides potential solutions for augmentation of clinical efficacy. A
      potential target for cancer immunotherapy is p53, as approximately 50% of ovarian
      cancer cells carry p53 mutations. Therefore we review the immunological and
      clinical responses observed in ovarian cancer patients vaccinated with p53
      targeting vaccines in particular. In most studies antigen-specific vaccine
      induced immunological responses were observed. Unfortunately, no clinical
      responses with significant reduction of tumor-burden have been reported. Based on
      the currently available results we emphasize the necessity of multimodality
      treatment of ovarian cancer, combining classical cytoreductive surgery, (neo)
      adjuvant chemotherapy, immunotherapy and/or targeted therapy.

PMID- 22591426
TI  - Advances in epithelial ovarian cancer therapy.
AB  - Advanced epithelial ovarian carcinoma has a dismal prognosis. Notwithstanding the
      good initial response to primary therapy, 75% of the patients with advanced
      disease will develop recurrent disease, causing approximately 60-80% of patients
      to die within 5 years of initial diagnosis. The chemotherapy regimens of the past
      century are summarized and the focus is on current systemic therapies and future
      developments in advanced epithelial ovarian cancer. Recently various promising
      treatments emerged. Attempts to optimize chemotherapy have included weekly
      scheduling of paclitaxel and intraperitoneal chemotherapy. Trials using
      angiogenesis inhibition and poly-ADP ribose polymerase (PARP) inhibitors show an
      advantage in progression-free survival while further overall survival data are
      awaited. Trabectedin, Hyperthermic intraperitoneal chemotherapy (HIPEC) and chemo
      immunotherapy may be become a promising therapy for the treatment of ovarian
      cancer. This Editorial encapsulates these new developments in ovarian cancer that
      are described extensively in the current theme issue Advances in Epithelial
      Ovarian Cancer Therapy.

PMID- 22591427
TI  - Ferritin and hyperactivity ratings in attention deficit hyperactivity disorder.
AB  - BACKGROUND: Iron is a co-factor of tyrosine hydroxylase which is a critical
      enzyme in dopamine synthesis. Dopamine has been implicated in the pathophysiology
      of attention deficit hyperactivity disorder (ADHD). Our objective was to
      investigate the association of ferritin level with parent and teacher ratings and
      cognitive measures after controlling for age, sex, ADHD subtype, comorbid
      conditions, hemoglobin, mean corpuscular volume and reticulocyte distribution
      width in a large sample. METHODS: The study included 713 children and adolescents
      with ADHD (613 boys; age 7-15 years). Conners' Parent Rating Scale (CPRS) and
      Conners' Teacher Rating Scale (CTRS) were obtained. In a subgroup of patients we
      conducted Digit Span, Digit Symbol, Trail-making Tests as measures of attention
      and executive functioning. RESULTS: Multiple regression analysis indicated that
      CPRS Hyperactivity score was significantly associated with ferritin level (B =
      0.12; t =-3.1; P < 0.01). Other CPRS and CTRS scores as well as cognitive
      measures were not associated with ferritin level. CONCLUSIONS: Although it is not
      possible to make an inference on causality in cross-sectional studies, the
      results of this largest-scale cross-sectional field study to date suggest that
      lower ferritin level might be associated with parent-reported hyperactivity after
      controlling for important confounding factors.

PMID- 22591430
TI  - Integration of oral health care into geriatric primary care: proposal for
      collaboration.

PMID- 22591429
TI  - Structural and functional consequences of the cardiac troponin C L48Q Ca(2+)
      sensitizing mutation.
AB  - Calcium binding to the regulatory domain of cardiac troponin C (cNTnC) causes a
      conformational change that exposes a hydrophobic surface to which troponin I
      (cTnI) binds, prompting a series of protein-protein interactions that culminate
      in muscle contraction. A number of cTnC variants that alter the Ca(2+)
      sensitivity of the thin filament have been linked to disease. Tikunova and Davis
      engineered a series of cNTnC mutations that altered Ca(2+) binding properties and
      studied the effects on the Ca(2+) sensitivity of the thin filament and
      contraction [Tikunova, S. B., and Davis, J. P. (2004) J. Biol. Chem. 279, 35341
      35352]. One of the mutations they engineered, the L48Q variant, resulted in a
      pronounced increase in the cNTnC Ca(2+) binding affinity and Ca(2+) sensitivity
      of cardiac muscle force development. In this work, we sought structural and
      mechanistic explanations for the increased Ca(2+) sensitivity of contraction for
      the L48Q cNTnC variant, using an array of biophysical techniques. We found that
      the L48Q mutation enhanced binding of both Ca(2+) and cTnI to cTnC. Nuclear
      magnetic resonance chemical shift and relaxation data provided evidence that the
      cNTnC hydrophobic core is more exposed with the L48Q variant. Molecular dynamics
      simulations suggest that the mutation disrupts a network of crucial hydrophobic
      interactions so that the closed form of cNTnC is destabilized. The findings
      emphasize the importance of cNTnC's conformation in the regulation of contraction
      and suggest that mutations in cNTnC that alter myofilament Ca(2+) sensitivity can
      do so by modulating Ca(2+) and cTnI binding.

PMID- 22591431
TI  - Caregivers' perceived comfort regarding oral care delivery in group homes: a
      pilot study.
AB  - The purpose of this study was to investigate the perceived comfort, behaviors,
      and barriers reported by group home caregivers while providing oral health care
      to individuals with special healthcare needs (SHCN). A 23-item survey was sent to
      428 caregivers in two group homes in Iowa. Bivariate and logistic regression
      models were used to analyze data (p <= 0.05). The overall response rate was 32%.
      An analysis of the bivariate and multivariate logistic regression indicated that
      caregivers who felt more comfortable providing care for individuals who verbally
      and physically resisted oral health care had worked more than 2 years at their
      current location (p = 0.0323), felt "neutral to very comfortable" brushing (p =
      0.0020) and flossing (p < 0.0001) the teeth of individuals with SHCN, and
      reported "sometimes to always" experiencing these individuals not opening their
      mouths (p = 0.0127). Comfort in providing oral care to individuals with SHCN
      appears to be linked to experience and length of time working with this
      population.

PMID- 22591432
TI  - Inspissated oral secretions and a review of their clinical, biological, and
      physiological significance.
AB  - People with some chronic diseases may dehydrate and develop thick, viscous
      inspissated oronasal secretions that include cellular debris. This material can
      lead to ductal or airway obstructions that can prove to be life threatening.
      Asthma, allergy with superinfection, cystic fibrosis, intubated ventilation, burn
      injuries, and medication-induced complications are discussed in this paper. Many
      patients with chronic debilitating conditions may also be unable to communicate,
      and so may be unable to verbally convey that they have a compromised airway or an
      obstruction. Therefore, it is essential to maintain hydration and good oral
      hygiene that not only addresses the teeth and prostheses, but also the oral
      mucosal surfaces. People who are institutionalized and bed-ridden, in particular,
      need to be closely monitored to prevent adverse sequellae. A daily oral sweep
      with a 4 * 4 surgical sponge moistened with chlorhexidine may prevent aspiration
      pneumonia or a fatality due to an airway obstruction. Human oronasal secretions
      are involved with immunity, digestion, lubrication, and speech. Saliva is the
      most volumetrically important. These secretions moisturize inspired and expired
      air but can lose water, causing an increase in viscosity. The viscous secretions
      trap particles, food debris, and bacterial colonies, thereby increasing
      inspissations that may obstruct the airway.

PMID- 22591433
TI  - Schwartz-Jampel syndrome: a review of the literature and case report.
AB  - Schwartz-Jampel syndrome (SJS) is a rare autosomal recessive skeletal dysplasia
      associated with myotonia. The manifestations of SJS include short stature,
      blepharophimosis, and skeletal anomalies. The combination of skeletal and
      muscular abnormalities may result in oro-dental manifestations such as atypical
      facies, with micrognathia, microstomia, pursed lips, crossbite, cleft palate, as
      well as mandibular hypoplasia, the risk of dentigerous cysts, and impacted teeth.
      The use of general anesthesia in patients with SJS is dangerous, as there is a
      risk of malignant hyperthermia. The purpose of this paper is to describe a 3-year
      old Chinese boy diagnosed with SJS at birth. His intra-oral examination revealed
      significant dental findings such as dentin defects with generalized attrition and
      hypodontia of the permanent dentition. Comprehensive dental treatment was
      provided at the same time as lower right limb surgery to reduce the potential
      complications with general anesthesia.

PMID- 22591434
TI  - Medical-dental findings and management of a child with infantile Refsum disease:
      a case report.
AB  - Infantile Refsum disease (IRD) is a peroxisome biogenesis disorder (PBD), and is
      part of a larger group of diseases called leukodystrophies, which are inherited
      conditions that damage the white matter of the brain and affect motor movements.
      Multiple signs and symptoms of IRD begin in infancy and progress through early
      childhood, including hearing and visual impairment, intellectual and growth
      impairment, seizures, liver involvement, and orofacial and dental abnormalities.
      This paper presents a case history of a 12-year-old female patient with IRD who
      underwent dental rehabilitation in the operating room under general anesthesia
      and includes a 2-year follow-up. Medical, dental, and management considerations
      in the care of this child's condition are presented. This paper also discusses
      the importance of a multidisciplinary approach in the management of children with
      special needs.

PMID- 22591435
TI  - Dental management of a pediatric patient with Burkitt lymphoma: a case report.
AB  - Recent advancements in the field of cancer diagnosis and chemotherapy have led to
      higher rates of survival for children with malignant tumors. More than 75% of
      pediatric patients diagnosed with malignancies survive more than 5 years. These
      advancements have resulted in additional responsibilities for dental
      professionals to diagnose, evaluate, prevent, stabilize, and manage the oral and
      dental problems that can compromise the quality of life of these children. This
      case report highlights the importance of professional and self-administered oral
      prophylactic measures and patient compliance in the successful oral
      rehabilitation of a pediatric patient with Burkitt lymphoma.

PMID- 22591436
TI  - Oral health care provided by Greek dentists to persons with physical and/or
      intellectual impairment.
AB  - This study evaluated Greek dentists' attitudes toward the provision of oral
      health care for persons with physical and intellectual impairment (PPII). A
      questionnaire was used to select information on dentists' socioeconomic data,
      their office characteristics, oral health care they performed, and their views
      about oral healthcare delivery for PPII. The final sample consisted of 534
      dentists. Descriptive statistics and Analysis of Variance (ANOVA) were used for
      the statistical analysis of the data. Most respondents were general practitioners
      (79.3%) providing oral health care to PPII, but 70% of the dentists had not been
      trained to treat them. In their opinion, oral health care for PPII demanded a lot
      of time and was hard to accomplish. Based on an evaluation of the results, this
      study suggests that continuing education and training of dentists to treat PPII
      are essential for this population in Greece.

PMID- 22591438
TI  - Sub-lethal effects of copper to benthic invertebrates explained by sediment
      properties and dietary exposure.
AB  - The next generation of sediment quality guidelines (SQGs) requires better
      established causal links between the chronic exposure and effects of metals from
      both dissolved and dietary sources. The potential for dietary exposure from
      sediment metals to cause toxic effects to benthic invertebrates is strongly
      influenced by the metal-binding properties of the sediments. For relatively
      oxidized sediments, sublethal effects of copper to the epibenthic deposit-feeding
      amphipod, Melita plumulosa, and the benthic harpacticoid copepod, Nitocra
      spinipes, were investigated. Effects on reproduction were strongly influenced by
      the properties of the sediments and sediment-bound copper was found to be the
      major contribution to the toxicity. For sediments with the same total copper
      concentrations, effects were less for sediments with greater concentrations of
      fine particles (<63 MUm sediment) or particulate organic carbon (OC). The OC
      normalized copper concentration in the <63 MUm sediment fraction provided a
      single effects threshold for all sediment types. For M. plumulosa and N.
      spinipes, the 10% effect concentrations (EC10s) were 5.2 and 4.8 mg <63 MUm Cu g(
      1) OC. These chronic EC10s indicate that a SQG of 3.5 mg <63 MUm Cu g(-1) OC,
      that was previously proposed based on a species sensitivity distribution of acute
      no effects thresholds data for 12 benthic organisms, will be protective for these
      species. The study confirms the appropriateness of using SQGs that vary with
      sediment properties and that SQGs of this form provide adequate protection for
      metal exposure via both dissolved and dietary exposure pathways.

PMID- 22591440
TI  - Pathways involved in human conscious vision contribute to obstacle-avoidance
      behaviour.
AB  - Human patients with visual field defects following damage to their primary visual
      cortex (V1) will often misperceive the midpoint of a horizontal line. They tend
      to shift the midpoint away from the real position towards their blind field. In
      patients with unilateral neglect, where midpoint shifts can also be observed,
      these perceptual errors do not lead to errors in an obstacle-avoidance task,
      which also requires the ability to find the midpoint between two obstacles. This
      dissociation in neglect patients was taken as evidence that obstacle-avoidance
      performance is guided by visual information from the dorsal visual stream.
      Recently it was shown that a patient with hemianopia could avoid an obstacle
      presented in his blind field. This suggests that obstacle-avoidance behaviour can
      be guided by subconscious vision alone involving a direct route from
      extrageniculate structures in the brain to dorsal stream areas. To investigate
      whether obstacle avoidance relies only on this subconscious route or also uses
      information from pathways involved in conscious vision, we examined the effect of
      the hemianopic shift on obstacle-avoidance behaviour. This shift is found in
      tasks where a conscious visual judgement is required and presumably arises in
      pathways underlying conscious vision (V1 and ventral stream areas). We compared
      the performance of six patients with left hemianopia with the performance of six
      patients with right hemianopia. We found a clear bias in both groups, which also
      affected obstacle-avoidance performance. It is thus concluded that obstacle
      avoidance does not bypass the system for conscious vision completely.

PMID- 22591439
TI  - Plant HDAC inhibitor chrysin arrest cell growth and induce p21WAF1 by altering
      chromatin of STAT response element in A375 cells.
AB  - BACKGROUND: Chrysin and its analogues, belongs to flavonoid family and possess
      potential anti-tumour activity. The aim of this study is to determine the
      molecular mechanism by which chrysin controls cell growth and induce apoptosis in
      A375 cells. METHODS: Effect of chrysin and its analogues on cell viability and
      cell cycle analysis was determined by MTT assay and flowcytometry. A series of
      Western blots was performed to determine the effect of chrysin on important cell
      cycle regulatory proteins (Cdk2, cyclin D1, p53, p21, p27). The fluorimetry and
      calorimetry based assays was conducted for characterization of chrysin as HDAC
      inhibitor. The changes in histone tail modification such as acetylation and
      methylation was studied after chrysin treatment was estimated by immuno
      fluorescence and western blot analysis. The expression of Bcl-xL, survivin and
      caspase-3 was estimated in chrysin treated cells. The effect of chrysin on p21
      promoter activity was studied by luciferase and ChIP assays. RESULTS: Chrysin
      cause G1 cell cycle arrest and found to inhibit HDAC-2 and HDAC-8. Chrysin
      treated cells have shown increase in the levels of H3acK14, H4acK12, H4acK16 and
      decrease in H3me2K9 methylation. The p21 induction by chrysin treatment was found
      to be independent of p53 status. The chromatin remodelling at p21WAF1 promoter
      induces p21 activity, increased STAT-1 expression and epigenetic modifications
      that are responsible for ultimate cell cycle arrest and apoptosis. CONCLUSION:
      Chrysin shows in vitro anti-cancer activity that is correlated with induction of
      histone hyperacetylation and possible recruitment of STAT-1, 3, 5 proteins at
      STAT (-692 to -684) region of p21 promoter. Our results also support an
      unexpected action of chrysin on the chromatin organization of p21WAF1 promoter
      through histone methylation and hyper-acetylation. It proposes previously unknown
      sequence specific chromatin modulations in the STAT responsive elements for
      regulating cell cycle progression negatively via the induction of the CDK
      inhibitor p21WAF1.

PMID- 22591441
TI  - Discovery of selective LRRK2 inhibitors guided by computational analysis and
      molecular modeling.
AB  - Mutations in the genetic sequence of leucine-rich repeat kinase 2 (LRRK2) have
      been linked to increased LRRK2 activity and risk for the development of
      Parkinson's disease (PD). Potent and selective small molecules capable of
      inhibiting the kinase activity of LRRK2 will be important tools for establishing
      a link between the kinase activity of LRRK2 and PD. In the absence of LRRK2
      kinase domain crystal structures, a LRRK2 homology model was developed that
      provided robust guidance in the hit-to-lead optimization of small molecule LRRK2
      inhibitors. Through a combination of molecular modeling, sequence analysis, and
      matched molecular pair (MMP) activity cliff analysis, a potent and selective lead
      inhibitor was discovered. The selectivity of this compound could be understood
      using the LRRK2 homology model, and application of this learning to a series of
      2,4-diaminopyrimidine inhibitors in a scaffold hopping exercise led to the
      identification of highly potent and selective LRRK2 inhibitors that were also
      brain penetrable.

PMID- 22591442
TI  - Synthesis of functional polyolefins using cationic bisphosphine monoxide
      palladium complexes.
AB  - The copolymerization of ethylene with polar vinyl monomers, such as vinyl
      acetate, acrylonitrile, vinyl ethers, and allyl monomers, was accomplished using
      cationic palladium complexes ligated by a bisphosphine monoxide (BPMO). The
      copolymers formed by these catalysts have highly linear microstructures and a
      random distribution of polar functional groups throughout the polymer chain. Our
      data demonstrate that cationic palladium complexes can exhibit good activity for
      polymerizations of polar monomers, in contrast to cationic alpha-diimine
      palladium complexes (Brookhart-type) that are not applicable to industrially
      relevant polar monomers beyond acrylates. Additionally, the studies reported here
      point out that phosphine-sulfonate ligated palladium complexes are no longer the
      singular family of catalysts that can promote the reaction of ethylene with many
      polar vinyl monomers to form linear functional polyolefins.

PMID- 22591443
TI  - Proton transport in a membrane protein channel: two-dimensional infrared spectrum
      modeling.
AB  - We model the two-dimensional infrared (2DIR) spectrum of a proton channel to
      investigate its applicability as a spectroscopy tool to study the proton
      transport process in biological systems. Proton transport processes in proton
      channels are involved in numerous fundamental biochemical reactions. However,
      probing the proton transport process at the molecular level is challenging,
      because of the limitation in both spatial and time resolution of the traditional
      experimental approaches. In this paper, we perform proton transport molecular
      dynamics simulations and model the amide I region of the 2DIR spectrum of a
      proton channel to examine its sensitivity to the proton transport process. We
      first report the position dependent proton transfer rates along the channel. The
      rates in the middle of the channel are larger than those in the entrance. In the
      presence of protons, we find that the antidiagonal line width of the 2DIR
      spectrum is larger, and the time evolution of the 2DIR spectrum is slower than
      that without proton. The time evolution of the 2DIR spectrum with different
      isotope-labeled residues is similar, even if the local proton transfer rates are
      different. This results from the proton hopping and the channel water rotation
      being collective mechanisms, and these effects are convoluted in the spectra.

PMID- 22591444
TI  - KIAA1549-BRAF fusions and IDH mutations can coexist in diffuse gliomas of adults.
AB  - KIAA1549-BRAF fusion gene and isocitrate dehydrogenase (IDH) mutations are
      considered two mutually exclusive genetic events in pilocytic astrocytomas and
      diffuse gliomas, respectively. We investigated the presence of the KIAA1549-BRAF
      fusion gene in conjunction with IDH mutations and 1p/19q loss in 185 adult
      diffuse gliomas. Moreover BRAF(v600E)  mutation was also screened. The KIAA1549
      BRAF fusion gene was evaluated by reverse-transcription polymerase chain reaction
      (RT-PCR) and sequencing. We found IDH mutations in 125 out 175 cases (71.4%).
      There were KIAA1549-BRAF fusion gene in 17 out of 180 (9.4%) cases and
      BRAF(v600E)  in 2 out of 133 (1.5%) cases. In 11 of these 17 cases, both IDH
      mutations and the KIAA1549-BRAF fusion were present, as independent molecular
      events. Moreover, 6 of 17 cases showed co-presence of 1p/19q loss, IDH mutations
      and KIAA1549-BRAF fusion. Among the 17 cases with KIAA1549-BRAF fusion gene 15
      (88.2%) were oligodendroglial neoplasms. Similarly, the two cases with
      BRAF(v600E)  mutation were both oligodendroglioma and one had IDH mutations and
      1p/19q co-deletion. Our results suggest that in a small fraction of diffuse
      gliomas, KIAA1549-BRAF fusion gene and BRAF(v600E)  mutation may be responsible
      for deregulation of the Ras-RAF-ERK signaling pathway. Such alterations are more
      frequent in oligodendroglial neoplasm and may be co-present with IDH mutations
      and 1p/19q loss.

PMID- 22591445
TI  - Genetic detection and characterization of atypical bovine pestiviruses in foetal
      bovine sera claimed to be of Australian origin.
AB  - Two European laboratories independently detected atypical bovine pestiviral
      nucleic acids in three commercial batches of foetal bovine serum (FBS) that was
      claimed by the producers to be of Australian origin. Additional batches of FBS
      were obtained directly from Australia to exclude possible contamination of the
      Australian FBS with that of South American origin during manufacturing/packaging
      in European countries. RT-PCR amplification of partial 5'untranslated region and
      the complete N(pro) gene yielded a specific band with expected size, which was
      confirmed by DNA sequencing. Bayesian analysis of sequence data demonstrated a
      closer phylogenetic relation of the newly detected atypical bovine pestiviruses
      to those of South American origin, which were related to the recognized bovine
      pestivirus species, bovine viral diarrhoea virus. Taken together, the results
      indicated the presence of atypical bovine pestiviruses in the Australian FBS, and
      most likely in Australian Continent.

PMID- 22591447
TI  - Mortality of HIV-infected and uninfected children in a longitudinal cohort in
      rural south-west Uganda during 8 years of follow-up.
AB  - OBJECTIVES: To determine the impact of HIV on child mortality and explore
      potential risk factors for mortality among HIV-infected and HIV-exposed
      uninfected children in a longitudinal cohort in rural Uganda. METHODS: From July
      2002 to March 2010, HIV-infected and HIV-exposed uninfected children aged 6 weeks
      13 years were enrolled in an open population-based clinical cohort.
      Antiretroviral therapy (ART) was introduced in 2005. Clinical and laboratory data
      were collected every 3 months. Person-years at risk were calculated from time of
      enrolment until earliest date of ART initiation, death or last visit. Cox
      regression was used to estimate hazard ratios (HR) for mortality. RESULTS: Eighty
      nine (30.2%) HIV-infected and 206 (69.8%) HIV-exposed but uninfected children
      were enrolled. Twenty-one children died. The mortality rate was six times higher
      in ART-naive HIV-infected children than in HIV-exposed but uninfected children
      (HR = 6.4, 95% CI = 2.4-16.6). Among HIV-infected children, mortality was highest
      in those aged <2 years. Decreasing weight-for-age Z (WAZ) score was the strongest
      risk factor for mortality among HIV-infected children (HR for unit decrease in
      WAZ = 2.6, 95% CI = 1.6-4.1). Thirty-five children (aged 7 months-15.6 years;
      median, 5.4 years) started ART. CONCLUSIONS: Mortality among HIV-infected
      children was highest among those aged <2 years. Intensified efforts to prevent
      mother-to-child transmission of HIV and ensure early HIV diagnosis and treatment
      are required to decrease child mortality caused by HIV in rural Africa.

PMID- 22591446
TI  - Static balance and function in children with cerebral palsy submitted to
      neuromuscular block and neuromuscular electrical stimulation: study protocol for
      prospective, randomized, controlled trial.
AB  - BACKGROUND: The use of botulinum toxin A (BT-A) for the treatment of lower limb
      spasticity is common in children with cerebral palsy (CP). Following the
      administration of BT-A, physical therapy plays a fundamental role in potentiating
      the functionality of the child. The balance deficit found in children with CP is
      mainly caused by muscle imbalance (spastic agonist and weak antagonist).
      Neuromuscular electrical stimulation (NMES) is a promising therapeutic modality
      for muscle strengthening in this population. The aim of the present study is to
      describe a protocol for a study aimed at analyzing the effects of NMES on
      dorsiflexors combined with physical therapy on static and functional balance in
      children with CP submitted to BT- A. METHODS/DESIGN: Protocol for a prospective,
      randomized, controlled trial with a blinded evaluator. Eligible participants will
      be children with cerebral palsy (Levels I, II and III of the Gross Motor Function
      Classification System) between five and 12 years of age, with independent gait
      with or without a gait-assistance device. All participants will receive BT-A in
      the lower limbs (triceps surae). The children will then be randomly allocated for
      either treatment with motor physical therapy combined with NMES on the tibialis
      anterior or motor physical therapy alone. The participants will be evaluated on
      three occasions: 1) one week prior to the administration of BT-A; 2) one week
      after the administration of BT-A; and 3) four months after the administration of
      BT-A (end of intervention). Spasticity will be assessed by the Modified Ashworth
      Scale and Modified Tardieu Scale. Static balance will be assessed using the
      Medicapteurs Fusyo pressure platform and functional balance will be assessed
      using the Berg Balance Scale. DISCUSSION: The aim of this protocol study is to
      describe the methodology of a randomized, controlled, clinical trial comparing
      the effect of motor physical therapy combined with NMES on the tibialis anterior
      muscle or motor physical therapy alone on static and functional balance in
      children with CP submitted to BT-A in the lower limbs. This study describes the
      background, hypotheses, methodology of the procedures and measurement of the
      results. TRIAL REGISTRATION: RBR5qzs8h.

PMID- 22591448
TI  - Sensory characteristics and consumer acceptability of beef stock containing the
      glutathione-xylose Maillard reaction product and/or monosodium glutamate.
AB  - This study was conducted to investigate the sensory characteristics and consumer
      acceptability of beef stock samples containing GSH-xylose Maillard reaction
      product (GX) and/or monosodium glutamate (MSG) with varying levels of salt
      (NaCl). The sensory characteristics of the beef stock samples were examined using
      a descriptive analysis. Total of 50 consumers evaluated overall acceptability and
      flavor intensities of beef odor, salty taste, beef flavor, and seasoning flavor
      in the samples. Samples containing both GX and MSG (GX-MSG), GX only (GX), and GX
      with higher salt level (GX-NaCl) had stronger "beef odor/flavor,""sulfur
      odor/flavor," and "chestnut odor/flavor" than those of the other samples, whereas
      beef stocks containing MSG, salt only (CON), and CON with higher salt level (CON
      NaCl) had stronger "potato odor/flavor" and "soy sauce odor/flavor" than those of
      the other samples. The consumers liked GX-MSG and MSG the most. Overall liking
      scores of GX-NaCl and CON-NaCl were significantly higher than that of CON. GX was
      not significantly preferred to CON. Partial least square regression results
      showed that salty, MSG, and sweet tastes had more significant impact on consumer
      perception of the beef and spice flavors and the liking score than strong beef
      odor/flavor of GX. However, high hedonic ratings of GX-MSG, which contained half
      the doses of GX and MSG used for the GX and MSG samples, suggest that the
      combination of GX and MSG had a synergistic effect on flavor enhancement of beef
      stock. PRACTICAL APPLICATION: Due to increasing needs for food products that
      provide more health benefits but maintain palatability, the food industry is
      looking for a new type of flavor enhancer. The Maillard reaction product of
      xylose and glutathione (GX), a tripeptide known to increase complexity and
      mouthfulness, was examined for its potential as a flavor enhancer. GX enhanced
      beef flavor significantly and salty taste somewhat at a weak suprathreshold
      level. With adjusting salty taste intensity by adding MSG at a weak
      suprathreshold level and/or increasing NaCl by 0.05% to 0.1%, GX significantly
      increased consumer acceptability.

PMID- 22591449
TI  - Construction of a fusion flagellin complex and evaluation of the protective
      immunity of it in red snapper (Lutjanus sanguineus).
AB  - AIMS: The main aims of this study were to construct a bivalent subunit vaccine
      containing flagellin flaA gene and flagellin flaB gene from Vibrio alginolyticus
      strain HY9901 and to explore the potential application of the fusion protein FlaA
      (G(4) S)(3)-FlaB as a vaccine candidate for red snapper (Lutjanus sanguineus).
      METHODS AND RESULTS: Flagellin gene flaA and flaB of V. alginolyticus were linked
      by gene SOEing (gene splicing by overlap extension) technology. The expression of
      the fusion gene flaA-(G(4)S)(3)-flaB in Escherichia coli BL21(DE3) was confirmed
      by SDS-PAGE. Western blot analysis showed that the fusion protein FlaA-(G(4)S)(3)
      FlaB, which was purified by affinity chromatography on Ni-NTA resin, had positive
      reaction with mouse anti-FlaA serum and mouse anti-FlaB serum, respectively. The
      immunoprotection of FlaA-(G(4) S)(3)-FlaB as a bivalent subunit vaccine was
      investigated in red snapper model by enzyme-linked immunosorbent assay (ELISA)
      and challenge test. Red snapper vaccinated with FlaA-(G(4) S)(3)-FlaB produced
      specific antibodies and were highly resistant to infection by virulent V.
      alginolyticus. CONCLUSIONS: The fusion gene flaA-(G(4) S)(3)-flaB from V.
      alginolyticus strain HY9901 was cloned by gene SOEing and was expressed in E.
      coli. This fusion protein FlaA-(G(4) S)(3)-FlaB is a good protective antigen of
      V. alginolyticus and should be considered as an effective vaccine candidate
      against infection by V. alginolyticus in red snapper. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Two flagellin genes, flaA and flaB, which are independent in structure
      and function, were first linked together by gene SOEing technology. The finding
      that red snapper did adequately respond to the fusion protein FlaA-(G(4) S)(3) 
      FlaB injection made it a promising candidate for vaccine treatment. To develop
      effective vaccine candidates against V. alginolyticus, more attention should be
      given to these immunogenic flagellins.

PMID- 22591450
TI  - Characterization and manipulation of mixed phase nanodomains in highly strained
      BiFeO3 thin films.
AB  - The novel strain-driven morphotropic phase boundary (MPB) in highly strained
      BiFeO(3) thin films is characterized by well-ordered mixed phase nanodomains
      (MPNs). Through scanning probe microscopy and synchrotron X-ray diffraction,
      eight structural variants of the MPNs are identified. Detailed polarization
      configurations within the MPNs are resolved using angular-dependent piezoelectric
      force microscopy. Guided by the obtained results, deterministic manipulation of
      the MPNs has been demonstrated by controlling the motion of the local probe.
      These findings are important for an in-depth understanding of the ultrahigh
      electromechanical response arising from phase transformation between competing
      phases, enabling future explorations on the electronic structure,
      magnetoelectricity, and other functionalities in this new MPB system.

PMID- 22591451
TI  - Response to: Radiological demonstration of spontaneous resolution of Type 1
      Chiari malformation in a 17-year-old patient.

PMID- 22591452
TI  - Primary calvarial Ewing's sarcoma presenting as a giant fungating skull tumour: a
      case report.
AB  - Giant calvarial Ewing's sarcoma is a rare entity. A 9-year-old girl presented
      with such a lesion, larger than her head and was fungating through the overlying
      skin. Surgical excision was done and the child was given chemotherapy. The child
      died after the second cycle. It is extremely uncommon to come across this disease
      in such an advanced stage.

PMID- 22591454
TI  - The race to the pole: how high-aspect ratio shape and heterogeneous environments
      limit phagocytosis of filamentous Escherichia coli bacteria by macrophages.
AB  - While bioengineers ask how the shape of diagnostic and therapeutic particles
      impacts their pharmacological efficiency, biodistribution, and toxicity,
      microbiologists suggested that morphological adaptations enable pathogens to
      perhaps evade the immune response. Here, a shape-dependent process is described
      that limits phagocytosis of filamentous  Escherichia coli  bacteria by
      macrophages: successful uptake requires access to one of the terminal bacterial
      filament poles. By exploiting micropatterned surfaces, we further demonstrate
      that microenvironmental heterogeneities can slow or inhibit phagocytosis. A
      comparison to existing literature reveals a common shape-controlled uptake
      mechanism for both high-aspect ratio filamentous bacteria and engineered
      particles.

PMID- 22591453
TI  - Dissociation of recombinant prion protein fibrils into short protofilaments:
      implications for the endocytic pathway and involvement of the N-terminal domain.
AB  - Fibril dissociation is necessary for efficient conversion of normal prion protein
      to its misfolded state and continued propagation into amyloid. Recent studies
      have revealed that conversion occurs along the endocytic pathway. To improve our
      understanding of the dissociation process, we have investigated the effect of low
      pH on the stability of recombinant prion fibrils. We show that under conditions
      that mimic the endocytic environment, amyloid fibrils made from full-length prion
      protein dissociate both laterally and axially to form protofilaments.
      Approximately 5% of the protofilaments are short enough to be considered soluble
      and contain ~100-300 monomers per structure; these also retain the biophysical
      characteristics of the filaments. We propose that protonation of His residues and
      charge repulsion in the N-terminal domain trigger fibril dissociation. Our data
      suggest that lysosomes and late endosomes are competent milieus for propagating
      the misfolded state not only by destabilizing the normal prion protein but also
      by accelerating the dissociation of fibrils into smaller structures that may act
      as seeds.

PMID- 22591455
TI  - A universal nucleoside with strong two-band switchable fluorescence and
      sensitivity to the environment for investigating DNA interactions.
AB  - With the aim of developing a new tool to investigate DNA interactions, a
      nucleoside analogue incorporating a 3-hydroxychromone (3HC) fluorophore as a
      nucleobase mimic was synthesized and incorporated into oligonucleotide chains. In
      comparison with existing fluorescent nucleoside analogues, this dye features
      exceptional environmental sensitivity switching between two well-resolved
      fluorescence bands. In labeled DNA, this nucleoside analogue does not alter the
      duplex conformation and exhibits a high fluorescence quantum yield. This probe is
      up to 50-fold brighter than 2-aminopurine, the fluorescent nucleoside standard.
      Moreover, the dual emission is highly sensitive to the polarity of the
      environment; thus, a strong shielding effect of the flanking bases from water was
      observed. With this nucleoside, the effect of a viral chaperone protein on DNA
      base stacking was site-selectively monitored.

PMID- 22591457
TI  - Solution processed micro- and nano-bioarrays for multiplexed biosensing.
AB  - This Feature article reports on solution dispensing methodologies  which enable
      the realization of multiplexed arrays at the micro- and  nanoscale for relevant
      biosensing applications such as drug screening  or cellular chips.

PMID- 22591456
TI  - Gastric tube resection due to metachronic cancer and a recurrence in anastomosis
      after Ivor-Lewis esophagectomy--case report.
AB  - Gastric tube after esophagectomy can be the site of local recurrence or the
      development of second primary tumor which implies poor prognosis. The study
      presents an extremely rare case of a patient after Ivor-Lewis esophagectomy for
      squamous cell carcinoma, in whom there was detected local recurrence in the
      anastomosis associated with metachronous primary tumor in gastric tube.
      Esophageal reresection with the upper part of the stomach was performed. Left
      colonic segment supplied by middle colic vessels transposed through retrosternal
      route was used as new esophageal substitute.

PMID- 22591458
TI  - The basal level ethylene response is important to the wall and endomembrane
      structure in the hypocotyl cells of etiolated Arabidopsis seedlings.
AB  - The sub-cellular events that occur during the ethylene-modulated cell elongation
      were characterized by examining the ultra-structure of etiolated Arabidopsis
      seedling hypocotyl cells. Preventing the basal level ethylene response
      facilitated cell elongation, and the cells exhibited wall loosening and
      separation phenotype. Nearby the wall separation sites were frequently associated
      with an increase in the cortical rough endoplasmic reticulum (rER) membranes, the
      presence of paramural bodies, and the circular Golgi formation. The cortical rER
      proliferation and circular Golgi phenotype were reverted by the protein
      biosynthesis inhibitor cycloheximide. The cortical rER membranes were longer when
      the ethylene response was prevented and shortened with elevated ethylene
      responses. Proteomic changes between wild type and the ethylene-insensitive
      mutant ethylene insensitive2 (ein2) seedling hypocotyls indicated that distinct
      subsets of proteins involving endomembrane trafficking, remodeling, and wall
      modifications were differentially expressed. FM4-64 staining supported the
      proteomic changes, which indicated reduced endocytosis activity with alleviation
      of the ethylene response. The basal level ethylene response has an important role
      in endomembrane trafficking, biological materials transport and maintenance of
      the endomembrane organization. It is possible that endomembrane alterations may
      partly associate with the wall modifications, though the biological significance
      of the alterations should be addressed in future studies.

PMID- 22591459
TI  - Regional variations in prevalence of postpartum depressive symptoms: population
      based survey.
AB  - The purpose of the present study was to verify that there are regional variations
      in the detection rate of postpartum depressive symptoms in mothers. A population
      based survey of all women who gave birth in Fushimi Ward, Kyoto City during the
      period 1 December 2008-31 October 2010 was carried out. The Edinburgh Postnatal
      Depression Scale (EPDS) was completed by 2567 mothers of infants to measure
      postpartum depressive symptoms. The detection rate of postpartum depressive
      symptoms was compared between five localities. A significant difference was found
      between the lowest detection rate of postpartum depressive symptoms (8.4%) and
      the highest (18.1%; P < 0.001). A significant positive correlation was found
      between the proportion of houses in the locality receiving public assistance and
      the detection rate of postpartum depressive symptoms. The detection rate of
      postpartum depressive symptoms shows regional variations, suggesting a
      relationship with the poverty rate.

PMID- 22591460
TI  - EnROL: a multicentre randomised trial of conventional versus laparoscopic surgery
      for colorectal cancer within an enhanced recovery programme.
AB  - BACKGROUND: During the last two decades the use of laparoscopic resection and a
      multimodal approach known as an enhanced recovery programme, have been major
      changes in colorectal perioperative care. Clinical outcome improves using
      laparoscopic surgery to resect colorectal cancer but until recently no
      multicentre trial evidence had been reported regarding whether the benefits of
      laparoscopy still exist when open surgery is optimized within an enhanced
      recovery programme. The EnROL trial (Enhanced Recovery Open versus Laparoscopic)
      examines the hypothesis that laparoscopic surgery within an enhanced recovery
      programme will provide superior postoperative outcomes when compared to
      conventional open resection of colorectal cancer within the same programme.
      METHODS/DESIGN: EnROL is a phase III, multicentre, randomised trial of
      laparoscopic versus open resection of colon and rectal cancer with blinding of
      patients and outcome observers to the treatment allocation for the first 7 days
      post-operatively, or until discharge if earlier. 202 patients will be recruited
      at approximately 12 UK hospitals and randomised using minimization at a central
      computer system in a 1:1 ratio. Recruiting surgeons will previously have
      performed >100 laparoscopic colorectal resections and >50 open total mesorectal
      excisions to minimize conversion. Eligible patients are those suitable for
      elective resection using either technique. Excluded patients include: those with
      acute intestinal obstruction and patients in whom conversion from laparoscopic to
      open procedure is likely. The primary outcome is physical fatigue as measured by
      the physical fatigue domain of the multidimensional fatigue inventory 20 (MFI-20)
      with secondary outcomes including postoperative hospital stay; complications;
      reoperation and readmission; quality of life indicators; cosmetic assessments;
      standardized performance indicators; health economic analysis; the other four
      domains of the MFI-20. Pathological assessment of surgical quality will also be
      undertaken and compliance with the enhanced recovery programme will be recorded
      for all patients. DISCUSSION: Should this trial demonstrate that laparoscopic
      surgery confers a significant clinical and/or health economic benefit this will
      further support the transition to this type of surgery, with implications for the
      training of surgeons and resource allocation. TRIAL REGISTRATION: ISRCTN48516968.

PMID- 22591461
TI  - Report on the 15th International Society of Blood Transfusion platelet immunology
      workshop.
AB  - BACKGROUND AND OBJECTIVES: The aim of the 15th ISBT Platelet Immunology Workshop
      was to evaluate the detection of free platelet-reactive autoantibodies from ITP
      patients by the use of a standardized MAIPA protocol, to compare sensitivity and
      specificity of antibody detection for anti-HPA-1a and serologically difficult-to
      assess antibodies against HPA-3, to identify whether anti-HPA-1a titration
      results can be compared between laboratories, and to evaluate HPA genotyping
      methods. MATERIALS AND METHODS: Workshop materials were shipped from the
      organizing laboratory in Giessen, Germany. Thirty laboratories from 19 countries
      participated. RESULTS: Results for the detection of autoantibodies differed
      greatly between the laboratories and no consensus was reached for one of the two
      sera. Detection and titration of antibodies against HPA-1a, in contrast, gave
      largely congruent results. Serologically difficult-to-assess antibodies
      recognizing HPA-3a and HPA-3b were not detected by many laboratories. For
      genotyping, good agreement was achieved. CONCLUSIONS: Detection of HPA-1a
      antibodies, titration of anti-HPA-1a, and HPA genotyping are well performed in
      most participating laboratories. The workshop has identified two specific areas
      with room and need for improvement: the detection of autoantibodies and the
      detection of HPA-3 alloantibodies. Recommendations of the Working Party on
      techniques that can help to overcome these problems are desirable.

PMID- 22591462
TI  - Impact of implant surface topography: a clinical study with a mean functional
      loading time of 85 months.
AB  - OBJECTIVE: Moderately rough, surfaced implants are widely used. Nevertheless data
      on long-term soft and hard tissue parameters are still conflicting. The purpose
      of this study was to evaluate peri-implant bone level and soft tissue integration
      of anodized vs. turned surfaced implants in the anterior mandible after a mean
      functional loading time of 85 months. METHODS: Of 114 edentulous patients invited
      for follow-up, 41,2% were available for recall. Forty-seven patients with a mean
      age of 71 +/- 9 years (14 men and 33 women) received 188 dental implants; All
      patients were edentulous and prosthetic rehabilitation was carried out by a bar
      retained overdenture. Radiographic peri-implant bone level was assessed twice at
      baseline and recall. Clinical examination contained peri-implant sounding (PPD,
      BoP) and indexing oral hygiene (mPI). RESULTS: From baseline up to 85 months two
      patients experienced implant loss (four implants), which corresponds to an
      overall-survival rate of 97.9%. No significant differences were found between
      implant surfaces concerning the clinical parameters, such as plaque, calculus,
      bleeding on probing and pocket probing depth. The moderately rough surfaced
      implants showed significantly less decrease in peri-implant bone level (1.53 +/-
      0.25 mm) than turned surfaced implants (2.42 +/- 0.34 mm) (P = 0.036). The
      interaction between the position of the implant and surface topography (P =
      0.037) as well as the site at the implant (P = 0.004) had a significant influence
      on bone level changes. CONCLUSION: Both surface topographies with bar-supported
      overdentures have excellent long-term clinical outcomes. Moreover, a moderately
      roughened, anodized surface has beneficial effects in the anterior lower jaw.

PMID- 22591464
TI  - Safety practices in Jordanian manufacturing enterprises within industrial
      estates.
AB  - This paper investigates occupational health and safety practices in manufacturing
      enterprises within Jordanian industrial estates. Response rates were 21.9%, 58.6%
      and 70.8% for small, medium and large sized enterprises, respectively. Survey
      results show that most companies comply with state regulations, provide necessary
      facilities to enhance safety and provide several measures to limit and control
      hazards. On the negative side, little attention is given to safety training that
      might be due to the lack of related regulations and follow-up, financial
      limitations or lack of awareness on the importance of safety training. In
      addition, results show that ergonomic hazards, noise and hazardous chemicals are
      largely present. Accident statistics show that medium enterprises have the
      highest accident cases per enterprise, and chemical industries reported highest
      total number of accidents per enterprise. The outcomes of this study establish a
      base for appropriate safety recommendations to enhance the awareness and
      commitment of companies to appropriate safety rules. 

PMID- 22591463
TI  - Possible effect of norepinephrine transporter polymorphisms on methylphenidate
      induced changes in neuropsychological function in attention-deficit hyperactivity
      disorder.
AB  - BACKGROUND: Dysregulation of noradrenergic system may play important roles in
      pathophysiology of attention-deficit/hyperactivity disorder (ADHD). We examined
      the relationship between polymorphisms in the norepinephrine transporter SLC6A2
      gene and attentional performance before and after medication in children with
      ADHD. METHODS: Fifty-three medication-naive children with ADHD were genotyped and
      evaluated using the continuous performance test (CPT). After 8-weeks of
      methylphenidate treatment, these children were evaluated by CPT again. We
      compared the baseline CPT measures and the post-treatment changes in the CPT
      measures based on the G1287A and the A-3081T polymorphisms of SLC6A2. RESULTS:
      There was no significant difference in the baseline CPT measures associated with
      the G1287A or A-3081T polymorphisms. After medication, however, ADHD subjects
      with the G/G genotype at the G1287A polymorphism showed a greater decrease in the
      mean omission error scores (p = 0.006) than subjects with the G/A or A/A
      genotypes, and subjects with the T allele at the A-3081T polymorphism (T/T or
      A/T) showed a greater decrease in the mean commission error scores (p = 0.003)
      than those with the A/A genotypes. CONCLUSIONS: Our results provide evidence for
      the possible role of the G1287A and A-3081T genotypes of SLC6A2 in
      methylphenidate-induced improvement in attentional performance and support the
      noradrenergic hypothesis for the pathophysiology of ADHD.

PMID- 22591465
TI  - The (TAAAA)n polymorphism of sex hormone-binding globulin gene is not associated
      with testicular maldescent.
AB  - The aim of this family-based study was to investigate the potential
      association/genetic linkage of the (TAAAA)n polymorphism of sex hormone-binding
      globulin gene proximal promoter with testicular maldescent (TMD). Genomic DNA was
      extracted from the peripheral blood of 487 subjects (174 index families): (i) 180
      children with all phenotypes of TMD, (ii) 307 parents (156 mothers and 151
      fathers). Conventional polymerase chain reaction amplification products were
      electrophoresed on 10% nondenaturating polyacrylamide gel and visualised by
      silver staining. After excluding ambiguous parental-child trios and most cases of
      index families with missing parental genotypes, 429 individuals were left for
      analysis: 138 completely typed nuclear families (five included a second affected
      child) and five child-parent couples (one parent missing). Eight fathers
      presented history of TMD, that is, a total of 156 cases with TMD were analysed.
      Alleles were analysed with the affected family-based control method and logistic
      regression-based extension of the transmission disequilibrium test for
      multiallelic loci. (TauAlphaAlphaAlphaAlpha)n polymorphism analysis revealed six
      alleles based on repeat numbers (n=5-10). No association/genetic linkage between
      the (TAAAA)n polymorphism and TMD was detected. Other factors should be
      investigated to potentially explain the genetic predisposition that seems to
      exist in at least a subgroup of these patients.

PMID- 22591466
TI  - Isolation and characterization of alpha,beta-unsaturated gamma-lactono-hydrazides
      from Streptomyces sp.
AB  - Two novel alpha,beta-unsaturated gamma-lactono-hydrazides, geralcin A (2) and
      geralcin B (3), were isolated from Streptomyces sp. LMA-545. This unusual
      scaffold consists of the condensation of alkyl-hydrazide with an alpha,beta
      unsaturated gamma-lactone, 3-(5-oxo-2H-furan-4-yl)propanoic acid (1), which was
      isolated from the same broth culture. Amberlite XAD-16 solid-phase extraction was
      used during the cultivation step, and the trapped compounds (1-3) were eluted
      from the resin with methanol. The structures were elucidated using (1)H, (13)C,
      and (15)N NMR spectroscopic analysis and high-resolution mass spectrometry.
      Geralcin B (3) was cytotoxic against MDA231 breast cancer cells with an IC(50) of
      5 MUM.

PMID- 22591467
TI  - Observation of a novel PFOS-precursor, the perfluorooctane sulfonamido ethanol
      based phosphate (SAmPAP) diester, in marine sediments.
AB  - The environmental occurrence of perfluorooctane sulfonate (PFOS) can arise from
      its direct use as well as from transformation of precursors ((N-alkyl
      substituted) perfluorooctane sulfonamides; FOSAMs). Perfluorooctane
      sulfonamidoethanol-based phosphate (SAmPAP) esters are among numerous potential
      PFOS-precursors which have not been previously detected in the environment and
      for which little is known about their stability. Based on their high production
      volume during the 1970s-2002 and widespread use in food contact paper and
      packaging, SAmPAP esters may be potentially significant sources of PFOS. Here we
      report for the first time on the environmental occurrence of SAmPAP diester in
      marine sediments from an urbanized marine harbor in Vancouver, Canada. SAmPAP
      diester concentrations in sediment (40-200 pg/g dry weight) were similar to those
      of PFOS (71-180 pg/g). A significant (p < 0.05) correlation was observed between
      SAmPAP diester and N-ethyl perfluorooctane sulfonamido acetate (an anticipated
      degradation product of SAmPAP diester). ?PFOS-precursor (FOSAM) concentrations in
      sediment (120-1100 pg/g) were 1.6-24 times greater than those of PFOS in
      sediment. Although SAmPAP diester was not detected in water, PFOS was observed at
      concentrations up to 710 pg/L. Among the per- and polyfluoroalkyl substances
      monitored in the present work, mean log-transformed sediment/water distribution
      coefficients ranged from 2.3 to 4.3 and increased with number of CF(2) units and
      N-alkyl substitution (in the case of FOSAMs). Overall, these results highlight
      the importance of FOSAMs as potentially significant sources of PFOS, in
      particular for urban marine environments.

PMID- 22591468
TI  - Editorial: The application of systems biology and bioinformatics methods in
      proteomics, transcriptomics and metabolomics (PART II).

PMID- 22591469
TI  - Computational studies on enzyme-substrate complexes of methanogenesis for
      revealing their substrate binding affinities to direct the reverse reactions.
AB  - In the present work, a combined approach of molecular modeling and systems
      biology was used to reveal how structural dynamics of enzymes involving in
      methanogenesis contributed to do reverse methanogenic reactions in methanotrophic
      archaea. The binding energies and molecular interaction distances of homology
      models and crystallographic structures of each enzyme with corresponding
      substrates were computed and its binding affinity compared with experimental
      enzyme kinetic data. The binding energies of enzyme model-substrate complexes in
      each reaction were favored to reverse reactions compared to PDB structure
      substrate complexes, supporting the existence of structural motions to direct
      substrate specificities in reverse order. Based on these, a proposed metabolic
      pathway for reverse methanogenesis in methanotrophic archaea was constructed, and
      its metabolic flux balance analyzed with experimental data of each enzyme
      reaction step. Methyl CoM reductase and methylene tetrahydromethanopterin
      reductase were assumed to determine the rate of the reverse methanogenesis
      reactions. Pathway model of this study should be concerned on understanding the
      cellular behavior of reverse methanogenesis in response to methane consumption
      from environment. Binding mode analysis of enzymes is thus directly correlated to
      molecular conservation and functional divergence of reverse methanogenesis, which
      lends strong support to reveal the molecular evolutionary hypothesis for
      methanotrophic archaea.

PMID- 22591470
TI  - Meta genome-wide network from functional linkages of genes in human gut microbial
      ecosystems.
AB  - The human gut microbial ecosystem (HGME) exerts an important influence on the
      human health. In recent researches, meta-genomics provided deep insights into the
      HGME in terms of gene contents, metabolic processes and genome constitutions of
      meta-genome. Here we present a novel methodology to investigate the HGME on the
      basis of a set of functionally coupled genes regardless of their genome origins
      when considering the co-evolution properties of genes. By analyzing these coupled
      genes, we showed some basic properties of HGME significantly associated with each
      other, and further constructed a protein interaction map of human gut meta-genome
      to discover some functional modules that may relate with essential metabolic
      processes. Compared with other studies, our method provides a new idea to extract
      basic function elements from meta-genome systems and investigate complex
      microbial environment by associating its biological traits with co-evolutionary
      fingerprints encoded in it.

PMID- 22591471
TI  - Using WPNNA classifier in ubiquitination site prediction based on hybrid
      features.
AB  - Ubiquitination, a reversible protein post-translational modification (PTM),
      occurs when an amide bond is formed between ubiquitin (a small protein) and the
      targeted protein. It involves in a wide variety of cellular processes and is
      associated with various diseases such as Alzheimer's disease. In order to
      understand ubiquitination at the molecular level, it is important to identify the
      ubiquitination site by which the ubiquitin binds to. Since experimental methods
      to determine ubiquitination sites are both expensive and time-consuming, it is
      necessary to develop in-silico methods to predict ubiquitination sites based on
      merely the sequential information of the target protein. In this paper, we apply
      a new classifier called weighted passive nearest neighbor algorithm (WPNNA) to
      predict the ubiquitination sites. WPNNA was demonstrated to be insensitive to the
      varied datum densities between different classes. A hybrid of features, including
      PSSM conservation scores, amino acid factors and disorder scores, are employed to
      code the protein fragments centered on the possible ubiquitination sites. The
      Mathew's correlation coefficient (MCC) of our predictor on a training dataset is
      0.169 with sensitivity of 31.6% and specificity of 82.9%, and on an independent
      test dataset is 0.403 with sensitivity of 64.3% and specificity of 75.7%. We
      compare our predictor with that of a recent published paper which also made
      predictions on the same datasets. Our predictor achieves much better
      sensitivities on both datasets than the paper and achieves much better MCC than
      the paper on the independent test dataset, indicating that the predictor based on
      WPNNA is as least a good complement to the current state of art in ubiquitination
      site prediction.

PMID- 22591472
TI  - FRKAS: knowledge acquisition using a fuzzy rule base approach to insight of DNA
      binding domains/proteins.
AB  - Numerous prediction methods of DNA-binding domains/proteins were proposed by
      identifying informative features and designing effective classifiers. These
      researches reveal that the DNA-protein binding mechanism is complicated and
      existing accurate predictors such as support vector machine (SVM) with position
      specific scoring matrices (PSSMs) are regarded as black-box methods which are not
      easily interpretable for biologists. In this study, we propose an ensemble fuzzy
      rule base classifier consisting of a set of interpretable fuzzy rule classifiers
      (iFRCs) using informative physicochemical properties as features. In designing
      iFRCs, feature selection, membership function design, and fuzzy rule base
      generation are all simultaneously optimized using an intelligent genetic
      algorithm (IGA). IGA maximizes prediction accuracy, minimizes the number of
      features selected, and minimizes the number of fuzzy rules to generate an
      accurate and concise fuzzy rule base. Benchmark datasets of DNA-binding domains
      are used to evaluate the proposed ensemble classifier of 30 iFRCs. Each iFRC has
      a mean test accuracy of 77.46%, and the ensemble classifier has a test accuracy
      of 83.33%, where the method of SVM with PSSMs has the accuracy of 82.81%. The
      physicochemical properties of the first two ranks according to their contribution
      are positive charge and Van Der Waals volume. Charge complementarity between
      protein and DNA is thought to be important in the first step of recognition
      between protein and DNA. The amino acid residues of binding peptides have larger
      Van Der Waals volumes and positive charges than those of non-binding ones. The
      proposed knowledge acquisition method by establishing a fuzzy rule-based
      classifier can also be applicable to predict and analyze other protein functions
      from sequences.

PMID- 22591473
TI  - A sequence-based approach for predicting protein disordered regions.
AB  - Protein disordered regions are associated with some critical cellular functions
      such as transcriptional regulation, translation and cellular signal transduction,
      and they are responsible for various diseases. Although experimental methods have
      been developed to determine these regions, they are time-consuming and expensive.
      Therefore, it is highly desired to develop computational methods that can provide
      us with this kind information in a rapid and inexpensive manner. Here we propose
      a sequence-based computational approach for predicting protein disordered regions
      by means of the Nearest Neighbor algorithm, in which conservation, amino acid
      factor and secondary structure status of each amino acid in a fixed-length
      sliding window are taken as the encoding features. Also, the feature selection
      based on mRMR (maximum Relevancy Minimum Redundancy) is applied to obtain an
      optimal 51-feature set that includes 39 conservation features and 12 secondary
      structure features. With the optimal 51 features, our predictor yielded quite
      promising MCC (Mathew's correlation coefficients): 0.371 on a rigorous benchmark
      dataset tested by 5-fold cross-validation and 0.219 on an independent test
      dataset. Our results suggest that conservation and secondary structure play
      important roles in intrinsically disordered proteins.

PMID- 22591474
TI  - Virus-ECC-mPLoc: a multi-label predictor for predicting the subcellular
      localization of virus proteins with both single and multiple sites based on a
      general form of Chou's pseudo amino acid composition.
AB  - Protein subcellular localization aims at predicting the location of a protein
      within a cell using computational methods. Knowledge of subcellular localization
      of viral proteins in a host cell or virus-infected cell is important because it
      is closely related to their destructive tendencies and consequences. Prediction
      of viral protein subcellular localization is an important but challenging
      problem, particularly when proteins may simultaneously exist at, or move between,
      two or more different subcellular location sites. Most of the existing protein
      subcellular localization methods specialized for viral proteins are only used to
      deal with the single-location proteins. To better reflect the characteristics of
      multiplex proteins, a new predictor, called Virus-ECC-mPLoc, has been developed
      that can be used to deal with the systems containing both singleplex and
      multiplex proteins by introducing a powerful multi-label learning approach which
      exploits correlations between subcellular locations and by hybridizing the gene
      ontology information with the dipeptide composition information. It can be
      utilized to identify viral proteins among the following six locations: (1) viral
      capsid, (2) host cell membrane, (3) host endoplasmic reticulum, (4) host
      cytoplasm, (5) host nucleus, and (6) secreted. Experimental results show that the
      overall success rates thus obtained by Virus-ECC-mPLoc are 86.9% for jackknife
      test and 87.2% for independent data set test, which are significantly higher than
      that by any of the existing predictors. As a user-friendly web-server, Virus
      ECCmPLoc is freely accessible to the public at the web-site
      http://levis.tongji.edu.cn:8080/bioinfo/Virus-ECC-mPLoc/.

PMID- 22591475
TI  - Inter- and intra-chain disulfide bond prediction based on optimal feature
      selection.
AB  - Protein disulfide bond is formed during post-translational modifications, and has
      been implicated in various physiological and pathological processes. Proper
      localization of disulfide bonds also facilitates the prediction of protein three
      dimensional (3D) structure. However, it is both time-consuming and labor
      intensive using conventional experimental approaches to determine disulfide
      bonds, especially for large-scale data sets. Since there are also some
      limitations for disulfide bond prediction based on 3D structure features,
      developing sequence-based, convenient and fast-speed computational methods for
      both inter- and intra-chain disulfide bond prediction is necessary. In this
      study, we developed a computational method for both types of disulfide bond
      prediction based on maximum relevance and minimum redundancy (mRMR) method
      followed by incremental feature selection (IFS), with nearest neighbor algorithm
      as its prediction model. Features of sequence conservation, residual disorder,
      and amino acid factor are used for inter-chain disulfide bond prediction. And in
      addition to these features, sequential distance between a pair of cysteines is
      also used for intra-chain disulfide bond prediction. Our approach achieves a
      prediction accuracy of 0.8702 for inter-chain disulfide bond prediction using 128
      features and 0.9219 for intra-chain disulfide bond prediction using 261 features.
      Analysis of optimal feature set indicated key features and key sites for the
      disulfide bond formation. Interestingly, comparison of top features between
      interand intra-chain disulfide bonds revealed the similarities and differences of
      the mechanisms of forming these two types of disulfide bonds, which might help
      understand more of the mechanisms and provide clues to further experimental
      studies in this research field.

PMID- 22591477
TI  - MicroRNA mediated network and DNA methylation in colorectal cancer.
AB  - Colorectal cancer (CRC) is one of the most malignant cancers. A growing number of
      studies have shown that both genetic and epigenetic play important roles in the
      etiology of CRC. Both microRNA (miRNA) and DNA methylation belong to the scope of
      epigenetic and there are complex regulatory mechanisms within miRNA and DNA
      methylation. We compiled 71 CRC related genes and 134 CRC related miRNAs. Then we
      identified 417 feed forward loops (FFLs) and 37 feedback loops (FBLs) among these
      genes, miRNAs and transcription factors (TFs). We constructed a network of miRNAs
      and TFs mediation for CRC utilizing these FFLs and FBLs. Statistical tests proved
      that these FFLs were significantly enriched in the CRC comparing to the
      esophageal cancer, breast cancer and randomly selected CRCmiRNA-gene pairs.
      Analysis of the network singled out 3 core genes, 2 core miRNAs and 5 core TFs.
      The KEGG enrichment and GO enrichment for the 2 core miRNA target genes indicated
      that they were significantly enriched in CRC related pathways. (Ex. MARK pathway,
      TGFbeta pathway and cell cycle) Through the investigation on methylation, we
      found that most of the CRC related genes and miRNAs were prone to be regulated by
      methylation. This study sheds lights on the regulatory mechanisms in CRC and we
      provide some insights on the epigenetic of CRC.

PMID- 22591478
TI  - Prediction of protein-protein interactions based on feature selection and data
      balancing.
AB  - Computational approaches are able to analyze protein-protein interactions (PPIs)
      from a different angle of view by complementing the experimental ones. And they
      are very efficient in determining whether two proteins can interact with each
      other. In this paper, KNNs (K-nearest neighbors) is applied to predict the PPIs
      by coding each protein with the physical and chemical properties of its residues,
      predicted secondary structures and amino acid compositions. mRMR (minimum
      redundancy maximum-relevance) feature selection is adopted to select a compact
      feature set, features of which are considered to be important for the
      determination of PPI-nesses. Because the size of the negative dataset (containing
      non-interactive protein pairs) is much larger than that of the positive dataset
      (containing interactive protein pairs), the negative dataset is divided into 5
      portions and each portion is combined with the positive dataset for one
      prediction. Thus 5 predictions are performed and the final results are obtained
      through voting. As a result, the prediction achieves an overall accuracy of
      0.8369 with sensitivity of 0.7356. The predictor, developed by this research for
      the prediction of the fruit fly PPI-nesses, is available for public use at
      http://chemdata.shu.edu.cn/ppip.

PMID- 22591479
TI  - HIV-1 protease cleavage site prediction based on two-stage feature selection
      method.
AB  - Knowledge of the mechanism of HIV protease cleavage specificity is critical to
      the design of specific and effective HIV inhibitors. Searching for an accurate,
      robust, and rapid method to correctly predict the cleavage sites in proteins is
      crucial when searching for possible HIV inhibitors. In this article, HIV-1
      protease specificity was studied using the correlation-based feature subset
      (CfsSubset) selection method combined with Genetic Algorithms method. Thirty
      important biochemical features were found based on a jackknife test from the
      original data set containing 4,248 features. By using the AdaBoost method with
      the thirty selected features the prediction model yields an accuracy of 96.7% for
      the jackknife test and 92.1% for an independent set test, with increased accuracy
      over the original dataset by 6.7% and 77.4%, respectively. Our feature selection
      scheme could be a useful technique for finding effective competitive inhibitors
      of HIV protease.

PMID- 22591480
TI  - A protein block based fold recognition method for the annotation of twilight zone
      sequences.
AB  - The description of protein backbone was recently improved with a group of
      structural fragments called Structural Alphabets instead of the regular three
      states (Helix, Sheet and Coil) secondary structure description. Protein Blocks is
      one of the Structural Alphabets used to describe each and every region of protein
      backbone including the coil. According to de Brevern (2000) the Protein Blocks
      has 16 structural fragments and each one has 5 residues in length. Protein Blocks
      fragments are highly informative among the available Structural Alphabets and it
      has been used for many applications. Here, we present a protein fold recognition
      method based on Protein Blocks for the annotation of twilight zone sequences. In
      our method, we align the predicted Protein Blocks of a query amino acid sequence
      with a library of assigned Protein Blocks of 953 known folds using the local pair
      wise alignment. The alignment results with z-value >= 2.5 and P-value <= 0.08 are
      predicted as possible folds. Our method is able to recognize the possible folds
      for nearly 35.5% of the twilight zone sequences with their predicted Protein
      Block sequence obtained by pb_prediction, which is available at Protein Block
      Export server.

PMID- 22591481
TI  - Prediction of turnover number of cellulose 1,4-beta-cellobiosidase.
AB  - The turnover number is an important parameter to distinguish whether an enzyme is
      practically workable. Therefore the prediction of turnover number of enzyme will
      reduce the workload to conduct time-consuming and costly experiments to determine
      the turnover number. However, no studies have been so far conducted to predict
      them with respect to cellulose 1,4-beta-cellobiosidase, which is an enzyme used
      in industries, especially in bio-fuel industry. It is important to develop
      methods to predict the turnover numbers of cellulose 1,4-beta-cellobiosidases
      from both wild-type and mutations. In this study, we used neural network models
      with different amino acid properties, pH levels, temperatures and substrates as
      inputs to predict the turnover number. The results show that 11 out of 25 amino
      acid properties analyzed can work as predictor and the amino acid distribution
      probability is the best one because it can reach smaller mean squared errors
      during convergence and higher correlation coefficient in two-layer neural network
      models. This study demonstrates the probability that the neural network model can
      approximately predict the turnover number of cellulose 1,4-betacellobiosidase.

PMID- 22591482
TI  - Computational methods for DNA-binding protein and binding residue prediction.
AB  - Protein-DNA interactions are involved in many essential biological processes such
      as transcription, splicing, replication and DNA repair. It is of great value to
      identify DNA-binding proteins as well as their binding sites in order to study
      the mechanisms of these biological processes. A number of experimental methods
      have been developed for the identification of DNA-binding proteins, such as
      DNAase foot printing, EMSA, X-ray crystallography, NMR spectroscopy and CHIP-on
      Chip. However, with the increasingly greater number of suspected protein-DNA
      interactions, identification by experimental methods is expensive, labor
      intensive and time-consuming. Hence, in the past decades researchers have
      developed many computational approaches to predict in silico the interactions of
      proteins and DNA. Machine learning technology has been widely used and become
      dominant in this field. In this article, we focus on reviewing recent machine
      learning-based progresses in DNA-binding protein and binding residue prediction
      methods, the most commonly used features in these predictions, machine learning
      classifier comparison and selection, evaluation method comparison, and existing
      problems and future directions for the field.

PMID- 22591483
TI  - In silico prediction of cytochrome P450-mediated site of metabolism (SOM).
AB  - Drug metabolism is a major consideration for modifying drug clearance and also a
      primary source for drug metabolite- induced toxicity. Cytochromes P450 (CYPs) are
      the major enzymes involved in drug metabolism and bioactivation, accounting for
      almost 75% of the total drug metabolism. Predicting the sites of cytochrome P450
      mediated metabolism of drug-like molecules using in silico methods would be
      highly beneficial and time efficient. An ideal system would enable researchers to
      make a confident elimination decision based purely on the structure of a new
      compound. In this review, several tools and models for predicting probable site
      of metabolism (SOM) have been compared and discussed. The methods are generally
      based on enzyme structure, ligand structure, and combined methods. Although all
      the methods have certain accuracy and considerable progress has been made, the
      results of the calculations still need careful inspection.

PMID- 22591484
TI  - The granulocytes in neutropenia 1 (GIN 1) study: a safety study of granulocytes
      collected from whole blood and stored in additive solution and plasma.
AB  - OBJECTIVE/AIM: To evaluate the safety of transfusing pooled, whole blood-derived
      granulocytes in additive solution and plasma (GASP) in 30 recipients. BACKGROUND:
      Demand for granulocytes in England has increased five-fold. With the advantages
      of reduced red cell, plasma and overall volume, GASP maintains function in vitro.
      METHODS AND MATERIALS: Observations were recorded prior to and post transfusion.
      Increments were recorded at 1 h and the following morning. Leucocyte antibody
      screening was undertaken prior to and at 1-6 months following transfusion.
      RESULTS: Thirty patients aged between 8 months and 68 years received 221 GASP in
      148 transfusion episodes. GASP contained an average of 1.0 * 10(10) granulocytes
      in 207 mL. Adults usually received two packs and children 10-20 mL kg(-1).
      Children and adults received a median [interquartile range (IQR)] dose of 12.5
      (9.1-25.3) and 19.7 (12.0-25.8) * 10(9) granulocytes per transfusion,
      respectively. There was one episode of transfusion-associated circulatory
      overload (TACO) in a patient with chronic cardiac failure following 600 mL of
      unpooled granulocytes, other fluids and one GASP. New leucocyte alloimmunisation
      occurred in 3/30 recipients 10%. No other significant reactions were reported.
      Median peripheral blood neutrophil increments at 1 h post transfusion were 0.06
      (IQR, 0.01-0.17) in children and (0.03) (IQR, 0-0.16) in adults. CONCLUSION: GASP
      has a similar safety profile to other sources of granulocytes for patients with
      refractory infection or in need of secondary prophylactic transfusion. Further
      studies are required to clarify the role of GASP in the treatment of neutropenic
      patients.

PMID- 22591485
TI  - Mannose receptor may be involved in small ruminant lentivirus pathogenesis.
AB  - Thirty-one sheep naturally infected with small ruminant lentiviruses (SRLV) of
      known genotype (A or B), and clinically affected with neurological disease,
      pneumonia or arthritis were used to analyse mannose receptor (MR) expression
      (transcript levels) and proviral load in virus target tissues (lung, mammary
      gland, CNS and carpal joints). Control sheep were SRLV-seropositive asymptomatic
      (n = 3), seronegative (n = 3) or with chronic listeriosis, pseudotuberculosis or
      parasitic cysts (n = 1 in each case). MR expression and proviral load increased
      with the severity of lesions in most analyzed organs of the SRLV infected sheep
      and was detected in the affected tissue involved in the corresponding clinical
      disease (CNS, lung and carpal joint in neurological disease, pneumonia and
      arthritis animal groups, respectively). The increased MR expression appeared to
      be SRLV specific and may have a role in lentiviral pathogenesis.

PMID- 22591487
TI  - 7th German Conference on Chemoinformatics: 25 CIC-Workshop Goslar, Germany.  6-8
      November 2011. Abstracts.

PMID- 22591486
TI  - Rapid purification and characterization of gamma-glutamyl-transpeptidase from
      shiitake mushroom (Lentinus edodes).
AB  - gamma-Glutamyl-transpeptidase (GGT) is one of the important enzymes in the
      pathway of odor formation in shiitake mushroom (Lentinus edodes). Rapid
      purification and characterization of GGT from shiitake mushroom were studied in
      this work. The GGT was purified 179-fold after 3 primary steps: precipitation by
      ammonium sulfate, isolation by Phenyl Sepharose 6 FF, and desalting by Sephadex G
      25. The enzyme, consisting of a small and a large subunit with Mr 28 KDa and 60
      KDa, respectively, is composed of 17 kinds of amino acids with the ratio of basic
      and acidic residues 1: 1.84, and its secondary structure was also determined by
      Fourier transform infrared spectroscopy. The properties of GGT were studied with
      gamma-glutamyl-p-nitroanilide as the substrate. The results showed Km value of
      2.601MUM, optimal temperature of 40  degrees C, and isoelectric point of 6.4. In
      addition, the activity of GGT was promoted by Na+, K+, and Ca2+ and inhibited by
      Cu2+, Ag+, Zn2+, and Fe3+. PRACTICAL APPLICATION: In this work, the gamma
      glutamyl-transpeptidase (GGT) from shiitake mushroom was purified with a simple
      scheme. Through the characterization of GGT, the relationship between endogenous
      formaldehyde and odor formation is to be clarified and assist in finding means of
      formaldehyde control in shiitake mushroom.

PMID- 22591489
TI  - Interview with a quality leader: John J. Kelly, MD on quality and patient safety.
      Interviewed by David J Shulkin.

PMID- 22591488
TI  - Transversus abdominis plane block for postoperative analgesia after cesarean
      delivery.
AB  - OBJECTIVE: The transversus abdominis plane (TAP) block is the ultrasound-guided
      placement of a peripheral nerve block in the abdominal wall for pain control. Our
      objective was to compare postoperative adjunctive oral narcotic use in women who
      underwent cesarean delivery and received the TAP block vs. those who received
      neuraxial narcotics. We hypothesize a decrease in narcotic use in women who
      received the TAP block. METHODS: Retrospective cohort study of women who received
      a TAP block for postoperative analgesia after cesarean compared to women who did
      not. The primary outcome was the total number of oral narcotic tablets
      administered between 24 and 48 h after surgery. An independent t-test and an
      analysis of covariance were employed to determine significant differences (P <
      0.05) between the cohorts and to adjust for confounders. RESULTS: The TAP block
      cohort utilized 30% less oral narcotic analgesia than the control cohort (3.8 +/-
      0.5 tablets, P < 0.001). After adjusting for confounders and the presence of
      antecedent labor, there remained a significant reduction in the total oral
      narcotic doses given to women who underwent a TAP block compared to other forms
      of analgesia. CONCLUSION: The TAP block is associated with decreased oral
      narcotic usage 24-48 h following cesarean delivery.

PMID- 22591490
TI  - Biographical sketch: Nosrat Ollah Ameli, MB, ChB (Hons), ChM (Birm), FICS, FRCS
      (Eng).
AB  - Nosrat Ollah Ameli (1913-2010) was one of the pioneers in Iranian neurosurgery.
      After training in England in the 1950s, Ameli returned to his country to found
      the Darioush Kabir Hospital, where he started the first neurosurgical ward in
      collaboration with Prof. E. Samiy. Here he applied his genius and innovation to
      develop unique approaches to the management of challenging neurosurgical
      techniques, in the context of limited resource available at that time. He started
      the training of neurosurgeons in Iran. He was internationally recognised being
      elected as a vice president of the World Federation of Neurosurgical Societies
      (WFNS). His efforts extended beyond neurosurgery to many other fields. He
      published extensively in international peer reviewed medical journals around the
      world and contributed to the foundation of Acta Medica Iranica journal, the first
      scientific medical journal in English published by Tehran University of Medical
      Sciences. His efforts to improve medical education in Iran continued even through
      his years of retirement. This article recounts Nosrat Ollah Ameli's many
      contributions to Iran's medical education as well as his achievements as a
      neurosurgeon.

PMID- 22591491
TI  - Redox properties and thiol reactivity of geldanamycin and its analogues in
      aqueous solutions.
AB  - Geldanamycin (GM), a benzoquinone ansamycin antibiotic, is a natural product
      inhibitor of Hsp90 with potent and broad anticancer properties, but with
      unacceptable levels of hepatotoxicity. Less toxic C17-substituted analogues have
      been synthesizedincluding 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) and
      the water-soluble 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17
      DMAG). Redox properties and thiol reactivity are central to the therapeutic and
      toxicologic effects of quinones, and the question arises as whether the extent of
      toxicity of GM, 17-AAG, and 17-DMAG is related to their redox potentials. Using
      pulse radiolysis, the one-electron redox potentials (vs NHE) at pH 7.0 of GM and
      17-AAG have been determined to be -62 +/- 7 mV and -273 +/- 8 mV, respectively,
      whereas a value of -194 +/- 6 mV has been previously published for 17-DMAG. The
      rate constants of the reaction of GM and its analogues with glutathione,
      cysteine, or dithiothreitol under anoxia at pH 7.4 followed the order GM > 17
      DMAG > 17-AAG, which correlates with the order of the redox potential of the
      quinone/semiquinone couple. Thus, GM reacts much faster with thiols compared to
      the less toxic 17-DMAG and 17-AAG, and is also expected to be more readily
      reduced by reductases to the respective semiquinone radical, which either
      decomposes to yield the respective hydroquinone or reduces oxygen to superoxide.
      Because both redox cycling and thiol reactivity have been associated with quinone
      toxicity, it is concluded that the toxicity of benzoquinone ansamycins is
      directly related to the redox potential of the quinone/semiquinone couple.

PMID- 22591492
TI  - Characteristics of highly impaired children with severe chronic pain: a 5-year
      retrospective study on 2249 pediatric pain patients.
AB  - BACKGROUND: Prevalence of pain as a recurrent symptom in children is known to be
      high, but little is known about children with high impairment from chronic pain
      seeking specialized treatment. The purpose of this study was the precise
      description of children with high impairment from chronic pain referred to the
      German Paediatric Pain Centre over a 5-year period. METHODS: Demographic
      variables, pain characteristics and psychometric measures were assessed at the
      first evaluation. Subgroup analysis for sex, age and pain location was conducted
      and multivariate logistic regression applied to identify parameters associated
      with extremely high impairment. RESULTS: The retrospective study consisted of
      2249 children assessed at the first evaluation. Tension type headache (48%),
      migraine (43%) and functional abdominal pain (11%) were the most common diagnoses
      with a high rate of co-occurrence; 18% had some form of musculoskeletal pain
      disease. Irrespective of pain location, chronic pain disorder with somatic and
      psychological factors was diagnosed frequently (43%). 55% of the children
      suffered from more than one distinct pain diagnosis. Clinically significant
      depression and general anxiety scores were expressed by 24% and 19% of the
      patients, respectively. Girls over the age of 13 were more likely to seek
      tertiary treatment compared to boys. Nearly half of children suffered from daily
      or constant pain with a mean pain value of 6/10. Extremely high pain-related
      impairment, operationalized as a comprehensive measure of pain duration,
      frequency, intensity, pain-related school absence and disability, was associated
      with older age, multiple locations of pain, increased depression and prior
      hospital stays. 43% of the children taking analgesics had no indication for
      pharmacological treatment. CONCLUSION: Children with chronic pain are a
      diagnostic and therapeutic challenge as they often have two or more different
      pain diagnoses, are prone to misuse of analgesics and are severely impaired. They
      are at increased risk for developmental stagnation. Adequate treatment and
      referral are essential to interrupt progression of the chronic pain process into
      adulthood.

PMID- 22591493
TI  - Is fast auditory change detection feature specific? An electrophysiological study
      in humans.
AB  - Recent oddball studies showed that auditory change detection responses exist in
      the first 50 ms after sound onset, upstream of mismatch negativity (MMN). We
      examined if these early responses could be elicited by feature-specific changes,
      meaning changes in the value of one attribute of a stimulus, regardless of
      whether other attributes of the stimulus are changing or not. We used a
      multifeature paradigm with four types of deviants: frequency, duration,
      intensity, and interaural time difference. In the middle latency range, only
      frequency deviants led to an enhanced Nb response. All four feature changes
      generated significant MMNs. Our results indicate that human brain is capable of
      detecting a feature-specific change for frequency attributes in the middle
      latency. The different levels of information being encoded in two separate event
      related potential time ranges support the notion of a hierarchical organization
      of auditory deviance detection.

PMID- 22591494
TI  - Novel systemic antibiotics in dermatology.
AB  - The treatment of bacterial skin infections has become challenging with the
      evolution of resistant species. As common antibiotics are losing efficacy, there
      is a pressing need for the discovery of new antibacterial agents. Only several
      systemic antibiotics have been approved for the treatment of skin infections in
      recent years. The expanding repertoire includes novel compounds structurally
      based on existing antibiotic classes, such as the glycopeptides, cephalosporins,
      and glycylcyclines. Antibiotics with completely unique mechanisms of action are
      being developed as members of the lipoprotein, oxazolidonone, and streptogramin
      classes. Most of these drugs require intravenous administration that limits their
      use. Future development should focus on more accessible routes of antibiotic
      administration, including oral, inhaled, or transdermal formulations.

PMID- 22591495
TI  - Update on topical antibiotics in dermatology.
AB  - Topical antibiotics are used for various purposes in dermatology. Some of the
      most common uses include treatment of acne, treatment and prevention of wound
      infection(s), impetigo or impetiginized dermatitis, and staphylococcal nasal
      carrier state. It is important for the dermatologist to be familiar with the
      spectrum of activity, the mechanism of action, and the variables that may
      interfere with the antibiotic of choice. The following discussion will review an
      update on topical antibiotic use in acne, wound care, impetigo, and in
      staphylococcal nasal carriers.

PMID- 22591496
TI  - Cutaneous and systemic adverse reactions to antibiotics.
AB  - Antibiotics cause a variety of cutaneous and systemic reactions. Reactions can
      range from mild exanthems to life-threatening toxic epidermal necrolysis. For
      this reason, it is important for dermatologists to recognize common cutaneous
      adverse reactions caused by specific antibiotics. This review highlights the
      clinical features and management of common adverse reactions to antibiotics.

PMID- 22591497
TI  - New antibiotic therapies for acne and rosacea.
AB  - Acne and rosacea compromise a substantial portion of the dermatology clinical
      practice. Over the past century, many treatment modalities have been introduced
      with antibiotics playing a major role. Today, both oral and topical antibiotics
      are used in the management of acne and rosacea, with several novel formulations
      and/or combination regimens recently introduced. The latest studies suggest anti
      inflammatory actions to be the most likely mechanism of antibiotics in acne and
      rosacea, shifting the focus to subantimicrobial-dose oral antibiotics and/or
      topical antibiotic regimens as the preferred first-line agents. Here we will
      discuss the most recent oral and topical antibiotic therapies available for
      treatment of acne and rosacea, with special focus on efficacy data, indication,
      dosing, and mechanism of action.

PMID- 22591498
TI  - Antibiotics used in nonbacterial dermatologic conditions.
AB  - The majority of nonbacterial dermatological conditions treated with antibiotics
      benefit from the anti-inflammatory properties of these medications, usually
      dapsone or tetracycline. Many other antimicrobials are used to treat
      noninfectious conditions. The following chapter is an overview of select
      noninfectious dermatological conditions for which antibiotics are used, with a
      focus on the most common antibiotics used for their nonantimicrobial properties.

PMID- 22591499
TI  - Antibiotic overuse and resistance in dermatology.
AB  - Antibiotics have a significant role in dermatology, treating a wide range of
      diseases, including acne, rosacea, inflammatory skin conditions and skin
      structure infections, such as cellulitis, folliculitis, carbuncles, and
      furuncles. Because of their consistent use, utility, and availability,
      antibiotics are susceptible to overuse within the medical practice, and, specific
      to this discussion, in the dermatologic setting. The issue of continuously
      increasing risk of antibiotic resistance remains an important concern to the
      dermatologist. The scope of this review will be to provide an overview of the
      common antibiotics used in the dermatologic setting with an emphasis on
      identifying areas of overuse, reported bacterial resistance, and discussion of
      clinical management aimed at decreasing antibiotic resistance.

PMID- 22591500
TI  - Intravenous antibiotics used in dermatology.
AB  - It is not common for dermatologists to use intravenous antibiotics in daily
      practice. However, there are several serious infections that may come to the
      attention of a dermatologist because of cutaneous signs and symptoms. It is
      important for dermatologists to be familiar with the presenting symptoms, various
      stages of disease, and treatment for such infections, as good outcomes are
      achieved by early recognition and use of appropriate therapy. The following
      section reviews the treatment, with a focus on intravenous antimicrobial therapy,
      for several serious infections important to dermatologists: syphilis, Rocky
      Mountain spotted fever, Lyme disease, cellulitis, methicillin-resistant
      Staphylococcus aureus, Vibrio vulnificans, and necrotizing fasciitis.

PMID- 22591501
TI  - Sequential use with imiquimod and surgery in extramammary Paget's disease.
AB  - Extramammary Paget's disease is an uncommon intraepithelial adenocarcinoma which
      occurs in areas rich in apocrine glands. Although surgery is the treatment of
      choice, numerous noninvasive treatments have been tried. There are studies that
      have demonstrated the efficacy of imiquimod to treat Extramammary Paget's
      disease, but we found no mention in the literature of its use as neoadjuvant
      therapy previous to surgery excision. We present a case of a large plaque of
      extramammary Paget's disease successfully treated with imiquimod and minor
      surgery of the residual disease.

PMID- 22591502
TI  - Photodynamic therapy with intralesional 5-aminolevulinic acid and intense pulsed
      light versus intense pulsed light alone in the treatment of acne vulgaris: a
      comparative study.
AB  - Despite the availability of many treatment modalities for acne vulgaris (AV), few
      of which provide excellent results. Photodynamic therapy (PDT) was shown to be an
      effective treatment especially when used with topical 5-aminolevulenic acid
      (ALA). We compared the efficacy and safety of PDT using intralesional ALA (IL
      ALA) with intense pulsed light (IPL) and IPL alone in the treatment of AV. This
      study was carried on 30 patients with nodulocystic and inflammatory AV on the
      face and back. The right side of the body was treated with IL-ALA plus IPL, while
      the left side was treated with IPL alone. All patients experienced a reduction in
      number of acne lesions on both sides of the body, but the reduction was
      significantly more in PDT side than IPL only side. Recurrence of the lesions was
      significantly more likely in the IPL only side. There was no statistically
      significant difference between the face and back lesions in drug side effects and
      recurrence of the lesions. We concluded that photodynamic therapy in this cohort
      is effective in the treatment of AV when combined with IL-ALA. It gives superior
      results compared with IPL alone with minimal and tolerable side effects and less
      recurrence rates.

PMID- 22591503
TI  - Carbon dioxide laser: first-line therapy in vulvar inflammatory linear verrucous
      epidermal nevus.
AB  - Inflammatory linear verrucous epidermal nevus (ILVEN) is normally associated with
      the failure of topical and systemic treatments and with recurrences on
      interruption of therapy. Many physical approaches have been used, but they
      generally resulted in varying rates of recurrence and unacceptable scarring. We
      reported a case of ILVEN treated with a single session CO(2)  laser treatment. In
      our experience, CO(2)  laser was quick, easy, effective, and safe; we therefore
      believe that this approach should be considered as a first-line surgical option
      in the treatment of genital ILVEN, particularly in cases of mucosal involvement.

PMID- 22591504
TI  - Pemphigus vulgaris treated with adalimumab: case study.
AB  - The study describes the case of a patient with a clinical and histopathological
      diagnosis of pemphigus vulgaris accompanied by severe side-effects of combined
      immunosuppressive therapy, who achieved a remission of the disease with
      adalimumab. Pemphigus vulgaris is a chronic blistering disease of the skin and
      mucous membranes. Before corticosteroids were introduced, mortality was high.
      Corticosteroids are currently used as first-line therapy. To reduce the dose of
      corticosteroids, therapeutic combinations with corticosteroid-sparing
      immunosuppressive agents are used. The therapy brings a number of complications
      due to its side effects. To achieve a remission of the disease by treating our
      patient with combined immunosuppressives, we administered adalimumab and achieved
      a very good clinical response.

PMID- 22591506
TI  - Metabolic activity in early tendon repair can be enhanced by intermittent
      pneumatic compression.
AB  - Since Achilles tendon healing is protracted, more knowledge of metabolites known
      to meet the demands for biosynthesis and proliferation is needed. We hypothesized
      that essential metabolites, glutamate, glucose, lactate, pyruvate and glycerol,
      are present and upregulated in healing Achilles tendons. We moreover hypothesized
      that adjuvant intermittent pneumatic compression (IPC), which increases blood
      flow, upregulates metabolite concentrations. Twenty patients with acute Achilles
      tendon rupture were recruited, operated, and included. The control group, 15
      patients, received plaster cast immobilization, while five patients received
      adjuvant foot IPC beneath the plaster cast. At 2 weeks postoperatively,
      microdialysis of the healing and contralateral intact Achilles tendons was
      followed by quantification of metabolites. Healing compared to intact tendons of
      the controls exhibited significantly increased concentrations (mM) of glutamate
      (60 +/- 14 vs 20 +/- 11), lactate (1.15 +/- 0.60 vs 0.64 +/- 0.35), and pyruvate
      (81 +/- 29 vs 35 +/- 25, MUM). Healing tendons of the IPC vs control group
      displayed higher levels of glutamate (84 +/- 15 vs 62 +/- 16) and glucose (3.44
      +/- 0.62 vs 2.62 +/- 0.72); (P < 0.05) and trends toward higher concentrations of
      pyruvate, lactate, and glycerol (P < 0.10). The present study demonstrates that
      early Achilles tendon repair entails and upregulates local essential metabolites.
      This metabolic response can, during tendon healing with plaster cast
      immobilization, be promoted by adjuvant IPC.

PMID- 22591507
TI  - High-speed mass measurement of nanoparticle and virus.
AB  - Until now, there have been no relatively easy methods to measure the mass and
      mass distributions of nanoparticles/viruses. In this work, we report the first
      set of measurements of mass and mass distributions for nanoparticles/viruses
      using a novel mass spectrometry technology. In the past, mass spectrometry was
      typically used to measure the mass of a particle or molecule with a mass less
      than 1,000,000 Da. We developed cell mass spectrometry that can measure the mass
      of a cell or a microparticle. Nevertheless, there is a gap for mass measurement
      methods in the mass region of a nanoparticle or virus (1 MDa to 1 GDa). Here, we
      developed a nanoparticle/virus mass spectrometry technique to make rapid and
      accurate mass and mass distribution measurements of nanoparticles/viruses. This
      technique should be valuable for the quality control of nanoparticle production
      and the identification of various viruses. In the future, this method can also
      serve to monitor drug delivery when nanoparticles are used as carriers.
      Furthermore, it may be possible to measure the degree of infection by measuring
      the number of viruses in specific cells or in plasma.

PMID- 22591508
TI  - Identification of caerulomycin A gene cluster implicates a tailoring
      amidohydrolase.
AB  - The biosynthetic gene cluster for caerulomycin A (1) was cloned and characterized
      from the marine actinomycete Actinoalloteichus cyanogriseus WH1-2216-6, which
      revealed an unusual hybrid polyketide synthase (PKS)/nonribosomal peptide
      synthetase (NRPS) system. The crmL disruption mutant accumulated caerulomycin L
      (2) with an extended L-leucine at C-7, implicating an amidohydrolase activity for
      CrmL. The leucine-removing activity was confirmed for crude CrmL enzymes.
      Heterologous expression of the 1 gene cluster led to 1 production in Streptomyces
      coelicolor.

PMID- 22591509
TI  - Child psychiatric consultation to pediatric inpatient services in Thailand.
AB  - Children with medical illnesses have significant levels of comorbid
      psychopathology. To understand the concern, and the area that needs to be
      addressed, the practice of child psychiatric inpatient consultation at Queen
      Sirikit National Institute of Child Health, Thailand was examined and appraised.
      Evaluation of the current practice pattern of psychiatric consultation is a
      crucial process in determining the next step of improving the quality of mental
      health care for sick children.

PMID- 22591510
TI  - Nonerosive gastroesophageal reflux disease and mild degree of esophagitis:
      comparison of symptoms endoscopic, manometric and pH-metric patterns.
AB  - BACKGROUND: Our aim in the present study was to compare patients presenting with
      gastroesophageal reflux disease in the presence or absence of mild-grade
      esophagitis (grade I or II according to the Savary-Miller classification).
      METHODS: Between 2005 and 2007, 215 patients with gastroesophageal reflux disease
      (67 with reflux associated with grade I or II esophagitis and 148 without
      esophagitis) were evaluated at the Department of Surgery, University Hospital Tor
      Vergata, Rome, and were included in the present study. The evaluations consisted
      of clinical interviews, endoscopy of the high digestive tract, esophageal
      manometry and pH monitoring. RESULTS: There was no significant difference between
      the two groups with regard to age, sex or symptoms. The incidence of heartburn
      associated with noncardiac chest pain was greater in the esophagitis group than
      in the dysphagia group. The incidence of hiatal hernia was similar in both
      groups. Although the motor pattern was similar in both groups, the length of the
      abdominal esophagus was greater in patients without esophagitis (1.6 cm vs 1.1
      cm; P < 0.05). The reflux pattern was nearly identical in both groups.
      CONCLUSIONS: Gastroesophageal reflux without esophagitis must be regarded not as
      a milder form of the disease but as part of a single disease. Furthermore, these
      patients often demonstrate lower rates of symptom improvement after antireflux
      treatment in comparison with patients with erosive esophagitis. Therefore,
      further trials to assess the treatment algorithm for these patients are
      warranted.

PMID- 22591511
TI  - Bisphenol s, a new bisphenol analogue, in paper products and currency bills and
      its association with bisphenol a residues.
AB  - As the evidence of the toxic effects of bisphenol A (BPA) grows, its application
      in commercial products is gradually being replaced with other related compounds,
      such as bisphenol S (BPS). Nevertheless, very little is known about the
      occurrence of BPS in the environment. In this study, BPS was analyzed in 16 types
      of paper and paper products (n = 268), including thermal receipts, paper
      currencies, flyers, magazines, newspapers, food contact papers, airplane luggage
      tags, printing paper, kitchen rolls (i.e., paper towels), and toilet paper. All
      thermal receipt paper samples (n = 111) contained BPS at concentrations ranging
      from 0.0000138 to 22.0 mg/g (geometric mean: 0.181 mg/g). The overall mean
      concentrations of BPS in thermal receipt papers were similar to the
      concentrations reported earlier for BPA in the same set of samples. A significant
      negative correlation existed between BPS and BPA concentrations in thermal
      receipt paper samples (r = -0.55, p < 0.0001). BPS was detected in 87% of
      currency bill samples (n = 52) from 21 countries, at concentrations ranging from
      below the limit of quantification (LOQ) to 6.26 MUg/g (geometric mean: 0.029
      MUg/g). BPS also was found in 14 other paper product types (n = 105), at
      concentrations ranging from <LOQ to 8.38 MUg/g (geometric mean: 0.0036 MUg/g;
      detection rate: 52%). The estimated daily intake (EDI) of BPS, through dermal
      absorption via handling of papers and currency bills, was estimated on the basis
      of concentrations and frequencies of the handling of papers by humans. The median
      and 95th percentile EDI values, respectively, were 4.18 and 11.0 ng/kg body
      weight (bw)/day for the general population and 312 and 821 ng/kg bw/day for
      occupationally exposed individuals. Among the paper types analyzed, thermal
      receipt papers were found to be the major sources of human exposure to BPS
      (>88%). To our knowledge, this is the first report on the occurrence of BPS in
      paper products and currency bills.

PMID- 22591512
TI  - Role of endolysosomes in HIV-1 Tat-induced neurotoxicity.
AB  - Combined anti-retroviral therapeutic drugs effectively increase the lifespan of
      HIV-1-infected individuals who then have a higher prevalence of HAND (HIV-1
      associated neurocognitive disorder). Soluble factors including HIV-1 proteins
      released from HIV-1-infected cells have been implicated in the pathogenesis of
      HAND, and particular attention has been paid to the HIV-1 Tat (transactivator of
      transcription) protein because of its ability to directly excite neurons and
      cause neuronal cell death. Since HIV-1 Tat enters cells by receptor-mediated
      endocytosis and since endolysosomes play an important role in neuronal cell life
      and death, we tested here the hypothesis that HIV-1 Tat neurotoxicity is
      associated with changes in the endolysosome structure and function and also
      autophagy. Following the treatment of primary cultured rat hippocampal neurons
      with HIV-1 Tat or as controls mutant-Tat or PBS, neuronal viability was
      determined using a triple staining method. Preceding observations of HIV-1 Tat
      induced neuronal cell death, we observed statistically significant changes in the
      structure and membrane integrity of endolysosomes, endolysosome pH and autophagy.
      As early as 24 h after HIV-1 Tat was applied to neurons, HIV-1 Tat accumulated in
      endolysosomes, endolysosome morphology was affected and their size increased,
      endolysosome membrane integrity was disrupted, endolysosome pH increased,
      specific activities of endolysosome enzymes decreased and autophagy was
      inhibited, as indicated by the significant changes in three markers for
      autophagy. In contrast, statistically significant levels of HIV-1 Tat-induced
      neuronal cell death were observed only after 48 h of HIV-1 Tat treatment. Our
      findings suggest that endolysosomes are involved in HIV-1 Tat-induced
      neurotoxicity and may represent a target for therapeutic intervention against
      HAND.

PMID- 22591514
TI  - The use of specific anti-growth factor antibodies to abrogate the oncological
      consequences of transfusion in head & neck squamous cell carcinoma: an in vitro
      study.
AB  - INTRODUCTION: Perioperative blood transfusion is associated with reduced
      prognosis in a number of solid malignancies. We investigate its role in a head &
      neck squamous cell cancer (HNSCC) cell lines. Growth of these cell lines was
      analogous to endothelial growth. Direct exposure to transfusion products
      exaggerated this effect. It was logical therefore to assess the effects of anti
      endothelial antibodies on this interaction. MATERIALS AND METHODS: Control
      (HUVEC) and tumour cell lines were exposed to transfusion products. The pre
      incubation of the transfusion product with anti-endothelial growth factors was
      assessed by a growth assay. Where appropriate cells were pre-incubated for 1 hour
      with 10 MUl of a mixture of 100 MUl of each and anti-ligand antibodies, the
      corresponding blood product supplement was incubated with 10 MUl of a mixture of
      100 MUl each of anti-ligand antibodies 1 hour before supplementation to the
      appropriate cell line. All results are representative of at least two independent
      experiments carried out in triplicate. RESULTS: The antibody did not directly
      reduce growth in the tumour cell line, however there was a significant reduction
      (p<0.001) in tumour cell line vascular mimicry caused by transfusion products pre
      incubation with anti-endothelial growth factor antibody. This was found in
      several other tumours. CONCLUSION: Perioperative blood transfusion is associated
      with reduced prognosis in a number of solid malignancies including HNSCC. However
      this phenomenon is abrogated by the use of anti-endothelial growth factor
      antibodies. This suggests that the original effect was mediated by the
      endothelial growth factor family.

PMID- 22591515
TI  - Dementia knowledge and attitudes of the general public in Northern Ireland: an
      analysis of national survey data.
AB  - BACKGROUND: This paper provides an overview of the findings from the dementia
      module of the 2010 Northern Ireland Life and Times (NILT) Survey: an annual
      survey recording public attitudes to major social policy issues. Northern
      Ireland, in line with many other developed countries, recently released a
      Dementia Strategy. The opportunity to explore the knowledge and attitudes of the
      general public to dementia at a national level in Northern Ireland is timely and
      valuable. This paper reports on an initial exploration of these attitudes, based
      on bivariate analysis across demographic groups. METHODS: Data were analyzed
      using SPSS (Version 19). Descriptive and summary statistics were produced. A
      series of categorical bivariate relationships were tested (chi-square) and tests
      of association (Cramer's V) were reported. We discuss both knowledge-related
      findings and attitudinal findings. RESULTS: We found that the general public in
      Northern Ireland have a reasonably good level of knowledge about dementia.
      However, attitudinal measures indicate the stereotyping and infantilization of
      people with dementia. CONCLUSIONS: This NILT module provides a unique source of
      data on attitudes to, and knowledge of, dementia. A key strength is that it
      provides statistically representative data with national level coverage. This
      information can be used to target public health education policies more
      effectively and to inform delivery of health and social services. The success of
      the module leads us to believe that it stands as a blue-print for collecting
      information on dementia in other social surveys.

PMID- 22591513
TI  - Palau'amine and related oroidin alkaloids dibromophakellin and
      dibromophakellstatin inhibit the human 20S proteasome.
AB  - We report herein that the oroidin-derived alkaloids palau'amine (1),
      dibromophakellin (2), and dibromophakellstatin (3) inhibit the proteolytic
      activity of the human 20S proteasome as well as the (i)20S immunoproteasome
      catalytic core. Palau'amine is found to prevent the degradation of
      ubiquitinylated proteins, including IkappaBalpha, in cell culture, which may be
      indicative of the potential mechanism by which these agents exhibit their
      exciting cytotoxic and immunosuppressive properties.

PMID- 22591517
TI  - Frontlines: are you secure?

PMID- 22591516
TI  - Species boundaries in tintinnid ciliates: a case study--morphometric variability,
      molecular characterization, and temporal distribution of Helicostomella species
      (Ciliophora, Tintinnina).
AB  - Tintinnids are a large group of planktonic ciliates with diverse morphologies.
      The range of variability in lorica shapes and sizes can be very high even within
      a single species depending on life stages and environmental conditions, which
      makes the delimitation of different species based on morphological criteria alone
      very difficult. Accordingly, comparisons of morphological and molecular
      variability in tintinnids are necessary to provide a pragmatic approach for
      establishing species boundaries within this diverse and poorly understood group.
      We investigated the temporal distribution of species of the hyaline tintinnid
      Helicostomella (Ciliophora, Tintinnina), which were collected daily from
      September 2008 to August 2009 in Jangmok Bay of Geoje Island on the south coast
      of Korea. Two forms - a long form and a short form, were discovered. The long
      form was found in cold waters in February and March whereas the short form
      occurred in warm waters from June to October. Thus, these two forms were
      seasonally isolated. However, all the morphological characteristics for these two
      forms overlap to some degree. A comparison of the small subunit (SSU) rDNA, ITS1
      5.8S-ITS2, and ITS2 sequences from two forms revealed 0.5%, 3.8%, and 5.6%
      divergences, respectively. Morever, one compensatory base change (CBC) and three
      hemi-CBCs were identified from ITS2 secondary structures of these two forms. All
      these data suggest that these two forms represent two distinct species despite
      their highly similar lorica morphology. The phylogenetic position of the genus
      Helicostomella was also examined using SSU rDNA sequences.

PMID- 22591520
TI  - Ten questions with... Jim Fedele.

PMID- 22591522
TI  - Ask George.

PMID- 22591523
TI  - Safe and secure? Healthcare in the cyberworld.

PMID- 22591524
TI  - Standing out from the crowd: master these practices and impress your boss.

PMID- 22591525
TI  - Healthcare technology management: AAMI survey sheds light on salaries, benefits.

PMID- 22591526
TI  - The human touch: learning that the job is about more than machines.

PMID- 22591527
TI  - Reprocessing recommendations: comparing AAMI standards with the 'Red Book'.

PMID- 22591528
TI  - Concept to reality: integrating technology in the hospital setting.

PMID- 22591529
TI  - Assurance cases: their use today and the challenges ahead.

PMID- 22591530
TI  - An overview: radiography for the imaging technician.

PMID- 22591531
TI  - Nursing executive sees need for user-friendly technology.

PMID- 22591532
TI  - Improving quality control in medical equipment inventory.

PMID- 22591533
TI  - The importance of HTM department staff.

PMID- 22591534
TI  - Radiation.

PMID- 22591535
TI  - The broad impact of EHR implementation.

PMID- 22591536
TI  - Anesthesia machines and digital blood pressure units.

PMID- 22591537
TI  - Medical equipment maintenance insurance.

PMID- 22591538
TI  - Medical device SALs and surgical site infections: a mathematical model.
AB  - It is commonly accepted that terminally sterilized healthcare products are rarely
      the source of a hospital-acquired infection (HAI). The vast majority of HAIs
      arise from human-borne contamination from the workforce, the clinical
      environment, less-than-aseptic handling techniques, and the patients themselves.
      Nonetheless, the requirement for a maximal sterility assurance level (SAL) of a
      terminally sterilized product has remained at 10(-6), which is the probability of
      one in one million that a single viable microorganism will be on a product after
      sterilization. This paper presents a probabilistic model that predicts choosing
      an SAL greater than 10(-6) (e.g. 10(-5) or 10(-4), and in some examples even 10(
      3) or 10(-2)) does not have a statistically significant impact on the incidence
      of surgical site infections (SSIs). The use of a greater SAL might allow new,
      potentially life-saving products that cannot withstand sterilization to achieve a
      10(-6) SAL to be terminally sterilized instead of being aseptically manufactured.

PMID- 22591540
TI  - PM stickers are 'a waste of time'.

PMID- 22591541
TI  - Paying for health care: moving beyond the user-fee debate.

PMID- 22591542
TI  - Equity in financing and use of health care in Ghana, South Africa, and Tanzania:
      implications for paths to universal coverage.
AB  - BACKGROUND: Universal coverage of health care is now receiving substantial
      worldwide and national attention, but debate continues on the best mix of
      financing mechanisms, especially to protect people outside the formal employment
      sector. Crucial issues are the equity implications of different financing
      mechanisms, and patterns of service use. We report a whole-system analysis-
      integrating both public and private sectors--of the equity of health-system
      financing and service use in Ghana, South Africa, and Tanzania. METHODS: We used
      primary and secondary data to calculate the progressivity of each health-care
      financing mechanism, catastrophic spending on health care, and the distribution
      of health-care benefits. We collected qualitative data to inform interpretation.
      FINDINGS: Overall health-care financing was progressive in all three countries,
      as were direct taxes. Indirect taxes were regressive in South Africa but
      progressive in Ghana and Tanzania. Out-of-pocket payments were regressive in all
      three countries. Health-insurance contributions by those outside the formal
      sector were regressive in both Ghana and Tanzania. The overall distribution of
      service benefits in all three countries favoured richer people, although the
      burden of illness was greater for lower-income groups. Access to needed,
      appropriate services was the biggest challenge to universal coverage in all three
      countries. INTERPRETATION: Analyses of the equity of financing and service use
      provide guidance on which financing mechanisms to expand, and especially raise
      questions over the appropriate financing mechanism for the health care of people
      outside the formal sector. Physical and financial barriers to service access must
      be addressed if universal coverage is to become a reality. FUNDING: European
      Union and International Development Research Centre.

PMID- 22591543
TI  - A field assessment of floor slipperiness in a student cafeteria.
AB  - Investigation of floor slipperiness is critical in studying the risk of slips and
      falls. This research conducted friction measurements and employee survey on floor
      slipperiness in a student cafeteria in a university in China in order to study
      the correlation between the two types of floor slipperiness measure. It was found
      that the fryer area in kitchen 1 and the meat defrost sink in kitchen 2 had
      significantly the lowest coefficient of friction (COF) values among all areas in
      the same kitchen. The results showed that the levels of friction on the floors in
      different areas in each kitchen were significantly different. Employee
      perceptions of floor slipperiness among areas were also significantly different.
      The level of friction and employee perception of floor slipperiness was highly
      correlated (rho = 0.87). This implies a good agreement between the two measures.
      A linear regression model was established to describe the relationship between
      the perceived floor slipperiness and the measured COF. The model was significant
      at p < 0.0001 with an R (2) of 0.59. 

PMID- 22591545
TI  - To be, or to be two, the question of dichotomizing variables.

PMID- 22591544
TI  - Lifestyle factors associated with overweight and obesity among Saudi adolescents.
AB  - BACKGROUND: A better understanding of the relationships between obesity and
      lifestyle factors is necessary for effective prevention and management of obesity
      in youth. Therefore, the objective of this study was to evaluate the associations
      between obesity measures and several lifestyle factors, including physical
      activity, sedentary behaviors and dietary habits among Saudi adolescents aged 14
      19 years. METHODS: This was a school-based cross-sectional study that was
      conducted in three cities in Saudi Arabia (Al-Khobar, Jeddah and Riyadh). The
      participants were 2906 secondary school males (1400) and females (1506) aged 14
      19 years, who were randomly selected using a multistage stratified cluster
      sampling technique. Measurements included weight, height, body mass index (BMI),
      waist circumference, waist/height ratio (WHtR), screen time (television viewing,
      video games and computer use), physical activity (determined using a validated
      questionnaire), and dietary habits (intake frequency per week). Logistic
      regression was used to examine the associations between obesity and lifestyle
      factors. RESULTS: Compared with non-obese, obese males and females were
      significantly less active, especially in terms of vigorous activity, had less
      favorable dietary habits (e.g., lower intake of breakfast, fruits and milk), but
      had lower intake of sugar-sweetened drinks and sweets/chocolates. Logistic
      regression analysis showed that overweight/obesity (based on BMI categories) or
      abdominal obesity (based on WHtR categories) were significantly and inversely
      associated with vigorous physical activity levels (aOR for high level = 0.69, 95%
      CI 0.41-0.92 for BMI and 0.63, 95% CI 0.45-0.89 for WHtR) and frequency of
      breakfast (aOR for < 3 days/week = 1.44; 95% CI 1.20-1.71 for BMI and 1.47; 95%
      CI 1.22-1.76 for WHtR) and vegetable (aOR for < 3 days/week = 1.29; 95% CI 1.03
      1.59 for WHtR) intakes, and consumption of sugar-sweetened beverages (aOR for < 3
      days/week = 1.32; 95% CI 1.08-1.62 for BMI and 1.42; 95% CI 1.16-1.75 for WHtR).
      CONCLUSIONS: The present study identified several lifestyle factors associated
      with obesity that may represent valid targets for the prevention and management
      of obesity among Saudi adolescents. Primary prevention of obesity by promoting
      active lifestyles and healthy diets should be a national public health priority.

PMID- 22591546
TI  - Catalase improves motility, vitality and DNA integrity of cryopreserved human
      spermatozoa.
AB  - Cryopreservation of human spermatozoa offers a pre-therapeutic possibility of
      preserving progenity in patients with testicular tumours. We aimed to investigate
      effects of cryopreservation and addition of catalase on sperm motility, vitality
      and DNA integrity in fresh and swim-up spermatozoa. Semen samples were collected
      from 50 fertile men. Each sample was divided into two parts. First part was
      subdivided into two equal aliquots: both cryopreserved with and without catalase.
      The second part was subdivided into two equal aliquots: both processed by swim up
      and then cryopreserved with or without catalase. Semen analyses, sperm vitality
      and sperm DNA integrity were performed. Sperm concentration showed significant
      decrease while percentage of progressive motility, sperm vitality and % of DNA
      damage showed significant increase in processed and cryopreserved processed
      samples when compared with fresh and cryopreserved fresh samples. There was no
      significant difference in sperm concentration while there was significant
      increase in % of progressive motility and sperm vitality and % of DNA damage
      showed significant decrease in samples with catalase when compared with samples
      without catalase (either fresh or processed). Catalase supplementation (fresh and
      processed) during cryopreservation results in better post-thawing percentage of
      progressive motility and percentage of sperm vitality and improved DNA integrity.

PMID- 22591547
TI  - A novel LC-MS application to investigate oxidation of peptides isolated from beta
      lactoglobulin.
AB  - Oxidation of beta-lactoglobulin (beta-Lg), a typical milk whey protein, was
      investigated by oxidizing its three tryptic peptides after separation and
      fractionation by preparative HPLC. Oxidation was performed with H2O2 and Fe(3+)
      in piperazine-1,4-bis(2-ethanesulfonic acid) (PIPES) buffer containing ascorbic
      acid, by keeping the samples in an oven of +37  degrees C for 14 days. Changes in
      the oxidized peptides were then analyzed with LC-ESI-QIT-MS. The peptides chosen
      were Ala-Leu-Pro-Met-His-Ile-Arg (ALPMHIR), Leu-Ile-Val-Thr-Gln-Thr-Met-Lys
      (LIVTQTMK) and Val-Leu-Val-Leu-Asp-Thr-Asp-Tyr-Lys (VLVLDTDYK), all containing
      amino acids of oxidative interest. Especially methionine (M) was prone to oxidize
      as well as dioxidize, along with tyrosine (Y), histidine (H) and/or proline (P).
      The ions m/z 854 [ALPMHIR + O], m/z 950 [LIVTQTMK + O] and m/z 966 [LIVTQTMK +
      2O] are considered very promising indicators of beta-Lg oxidation. Consequently,
      this study proposes a novel approach in peptide oxidation research through
      monitoring the oxidation markers identified with the LC-MS(n). 

PMID- 22591548
TI  - Modelling homogeneous and heterogeneous microbial contaminations in a powdered
      food product.
AB  - The actual physical distribution of microorganisms within a batch of food
      influences quantification of microorganisms in the batch, resulting from sampling
      and enumeration by microbiological tests. Quantification may be most accurate for
      batches in which microorganisms are distributed homogeneously. However, when the
      distribution is non-homogeneous, quantification may result in an under-, or
      overestimation. In the case of pathogens being non-homogeneously distributed,
      this heterogeneity will impact on public health. Enumeration data are commonly
      modelled by the Lognormal distribution. Although the Lognormal distribution can
      model heterogeneity, it does not allow for complete absence of microorganisms.
      Studies that validate the appropriateness of using Lognormal or other statistical
      distributions are scarce. This study systematically investigated laboratory and
      industrial scale batches of powdered infant formula, modelled the enumeration
      data using a range of statistical distributions, and assessed the appropriateness
      of individual models. For laboratory scale experiments, batches of milk powder
      were contaminated by distributing similar numbers of cells of Cronobacter
      sakazakii either homogeneously throughout a batch of milk powder or by
      distributing the cells in a localised part of the batch. Each batch was then
      systematically sampled and the distribution determined by enumerating the
      samples. By also enumerating the remainder of the batch, a balance could be made
      of the total number of microorganisms added and of the number retrieved from a
      batch. Discrete, as well as continuous statistical distributions, were fitted to
      enumeration data and the parameters estimated by Maximum Likelihood. The data
      were fitted both as censored and uncensored data. Enumeration data obtained for
      an industrial batch of powdered infant formula were investigated in this way as
      well. It was found that Normal, Poisson and Zero-Inflated Poisson distributions
      fitted the data sets very poorly. In case of homogeneous contamination, there was
      not a notable difference between the ability of Negative Binomial, Poisson
      Lognormal, Weibull, Gamma, and Lognormal distributions to model the data.
      Overall, either the Negative Binomial distribution or the Poisson-Lognormal
      distribution fitted the data best in the 10 batches studied, especially when part
      of a data set contained zeros and/or the numbers were low. The Negative Binomial
      fitted the laboratory batches best and the Poisson-Lognormal fitted the
      industrial batch best.

PMID- 22591549
TI  - Mycobacterium avium subsp. paratuberculosis survival during fermentation of
      soured milk products detected by culture and quantitative real time PCR methods.
AB  - Mycobacterium avium paratuberculosis (MAP), etiological agent of paratuberculosis
      in ruminants, is able to survive extreme conditions like very low pH (stomach),
      high temperature (pasteurization) or low temperature (refrigerated storage).
      Cheese, infant powder milk, cream and other milk and dairy products might thus be
      considered as possible sources of MAP for humans. The aim of this study was to
      investigate the survival of two MAP field isolates during fermentation of three
      different types of soured milk products (SMP; yogurt, acidophilus milk and kefir)
      under laboratory conditions. Pasteurized MAP-free milk was artificially
      contaminated with 10(6)MAPcells/mL and survival and absolute numbers of MAP were
      monitored during fermentation (4 or 16 h) and after six weeks of storage at 4
      degrees C by culture and quantitative real time PCR (qPCR). Viability of MAP was
      determined by culture using Herrold's egg yolk medium and Middlebrook 7H10 with
      antibiotics, supplemented with Mycobactin J and incubated at 37 degrees C for up
      to 12 weeks. The absolute numbers of MAP were quantified by previously published
      qPCR assays targeting F57 and IS900 loci in MAP genome. We herein confirm that
      MAP can survive pH reduction, however, longer exposure to pH below 4 in SMP seems
      to be critical because it inhibits growth. Therefore, it is suggested that
      probiotic cultures that can decrease pH below 4 during fermentation could provide
      better inactivation of MAP in SMP.

PMID- 22591550
TI  - Evidence of increased skin irritation after wet work: impact of water exposure
      and occlusion.
AB  - BACKGROUND: Exposure to humid environments/water and prolonged glove occlusion
      are both believed to cause irritant contact dermatitis. OBJECTIVES: To study the
      effects of different forms of wet work, especially the differences between water
      exposure and occlusion, by using an experimental model simulating occupational
      wet work. METHODS: The responses to water exposure and occlusion over multiple
      daily exposure periods for 7 days were compared in 73 volunteers. After the 1
      week exposure, the sites were irritated with sodium lauryl sulfate (SLS).
      Comparison was performed via visual inspection and bioengineering methods.
      RESULTS: Whereas occlusion did not induce measurable alterations in skin
      physiology, water exposure for more than 3 hr daily caused a significant increase
      in transepidermal water loss (TEWL) as compared with the control areas. SLS
      irritation of the previously occluded and the water-exposed sites induced higher
      TEWL and clinical scores in a time-dependent fashion as compared with the control
      areas, with more pronounced reactions in the water-exposed sites than in the
      occluded sites. CONCLUSION: Both previous occlusion and water exposure were
      capable of inducing higher susceptibility to SLS irritation. Skin hydration by
      occlusion had a different biological effect than water exposure. Short occlusions
      seem to harm the skin less than water exposure for the same duration.

PMID- 22591551
TI  - [Comparison between aquatic-biodanza and stretching for improving quality of life
      and pain in patients with fibromyalgia].
AB  - OBJECTIVE: To determine the level of improvement, as regards pain, impact on
      fibromyalgia and depression, achieved by patients with fibromyalgia by comparing
      aquatic biodanza and stretching exercises. DESIGN: Randomised controlled trial
      with two intervention groups. LOCATION: Five health centres (Almeria). PATIENTS:
      A total of 82 fibromyalgia patients between 18 and 65 years old, diagnosed by
      American College of Rheumatology criteria, were included, with 12 patients
      declining to take part in the study. The 70 remaining patients were randomly
      assigned to two groups of 35 patients each: aquatic biodanza and stretching
      exercises. Those who did not attend in at least 14 sessions or changed their
      treatment during the studio were excluded. The final sample consisted of 19
      patients in aquatic biodanza group and 20 in stretching group. The limitations of
      the study included, the open evaluation design and a sample size reduced by
      defaults. MAIN MEASURES: The outcome measures were sociodemographic data, quality
      of life (Fibromyalgia Impact Questionnaire), pain (McGill-Melzack questionnaire;
      and Visual Analogue Scale), pressure algometry (Wagner FPI10 algometer) and
      depression (Beck Inventory). These were carried out before and after a 12-week
      therapy. RESULTS: The mean age of the sample was 55.41 years. The mean period
      from diagnosis was 13.44 years. The sample consisted mainly of housewives. There
      were significant differences (P<.05) between groups, in pain (P<.01),
      fibromyalgia impact (P<.01), and depression (P<.04) after the treatment.
      CONCLUSIONS: The biodanza aquatic exercises improve pain and quality of life in
      fibromyalgia patients.

PMID- 22591553
TI  - Evaluation of cardiac functions in term small for gestational age newborns with
      mild growth retardation: a serial conventional and tissue Doppler imaging
      echocardiographic study.
AB  - BACKGROUND: The aim of this study is to evaluate the cardiac functions of term
      small for gestational age (SGA) babies with mild growth retardation by
      echocardiography during the postnatal period. METHODS AND RESULTS: Thirty term
      SGA (2271+/-207 g/38-41 weeks (mean 39.5 weeks)) and 30 term AGA (3298+/-338 g/38
      41 weeks (mean 39 weeks)) newborns as the control group, with normal general
      health status and with no nutritional problems were evaluated at three time
      points, on the 3rd postnatal day, at the 3rd and the 6th months. In the initial
      analysis, heart rate, left ventricular end diastolic diameter index (LVEdDI),
      cardiac index (CI), all E/A, Em/Am and E/Em ratios, pulsed wave Doppler
      myocardial performance index (MPI), and tissue Doppler imaging MPI values were
      higher in SGA babies than the control group. In the last analysis, only heart
      rate, LVEdDI and CI values were different between SGA and control groups.
      CONCLUSIONS: Systolic and diastolic cardiac dysfunctions were determined in SGA
      babies with mild growth retardation during the first 6 months of postnatal
      period. Any disease that affects the hemodynamic stability of these patients
      during postnatal period may lead to early progressive deterioration in cardiac
      functions. Furthermore, many of the cardiac functions of these babies have been
      improved about the 6th month period, and high levels of heart rate and LVEdDI may
      be suggested as an indicator of cardiac remodeling.

PMID- 22591552
TI  - Variation in regulator of G-protein signaling 17 gene (RGS17) is associated with
      multiple substance dependence diagnoses.
AB  - BACKGROUND: RGS17 and RGS20 encode two members of the regulator of G-protein
      signaling RGS-Rz subfamily. Variation in these genes may alter their
      transcription and thereby influence the function of G protein-coupled receptors,
      including opioid receptors, and modify risk for substance dependence. METHODS:
      The association of 13 RGS17 and eight RGS20 tag single nucleotide polymorphisms
      (SNPs) was examined with four substance dependence diagnoses (alcohol (AD),
      cocaine (CD), opioid (OD) or marijuana (MjD)] in 1,905 African Americans (AAs:
      1,562 cases and 343 controls) and 1,332 European Americans (EAs: 981 cases and
      351 controls). Analyses were performed using both chi2 tests and logistic
      regression analyses that covaried sex, age, and ancestry proportion. Correlation
      of genotypes and mRNA expression levels was assessed by linear regression
      analyses. RESULTS: Seven RGS17 SNPs showed a significant association with at
      least one of the four dependence traits after a permutation-based correction for
      multiple testing (0.003<=P(empirical)<=0.037). The G allele of SNP rs596359, in
      the RGS17 promoter region, was associated with AD, CD, OD, or MjD in both
      populations (0.005<=P(empirical)<=0.019). This allele was also associated with
      significantly lower mRNA expression levels of RGS17 in YRI subjects (P = 0.002)
      and non-significantly lower mRNA expression levels of RGS17 in CEU subjects (P =
      0.185). No RGS20 SNPs were associated with any of the four dependence traits in
      either population. CONCLUSIONS: This study demonstrated that variation in RGS17
      was associated with risk for substance dependence diagnoses in both AA and EA
      populations.

PMID- 22591554
TI  - Microtermolides A and B from termite-associated Streptomyces sp. and structural
      revision of vinylamycin.
AB  - Microtermolides A (1) and B (2) were isolated from a Streptomyces sp. strain
      associated with fungus-growing termites. The structures of 1 and 2 were
      determined by 1D- and 2D-NMR spectroscopy and high-resolution mass spectrometry.
      Structural elucidation of 1 led to the re-examination of the structure originally
      proposed for vinylamycin (3). Based on a comparison of predicted and experimental
      (1)H and (13)C NMR chemical shifts, we propose that vinylamycin's structure be
      revised from 3 to 4.

PMID- 22591555
TI  - Examining the role of phosphate in glycosyl transfer reactions of Cellulomonas
      uda cellobiose phosphorylase using D-glucal as donor substrate.
AB  - Cellobiose phosphorylase from Cellulomonas uda (CuCPase) is shown to utilize D
      glucal as slow alternative donor substrate for stereospecific glycosyl transfer
      to inorganic phosphate, giving 2-deoxy-alpha-D-glucose 1-phosphate as the
      product. When performed in D(2)O, enzymatic phosphorolysis of D-glucal proceeds
      with incorporation of deuterium in equatorial position at C-2, implying a
      stereochemical course of reaction where substrate becomes protonated from below
      its six-membered ring through stereoselective re side attack at C-2. The proposed
      catalytic mechanism, which is supported by results of docking studies, involves
      direct protonation of D-glucal by the enzyme-bound phosphate, which then performs
      nucleophilic attack on the reactive C-1 of donor substrate. When offered D
      glucose next to D-glucal and phosphate, CuCPase produces 2-deoxy-beta-D-glucosyl
      (1->4)-D-glucose and 2-deoxy-alpha-D-glucose 1-phosphate in a ratio governed by
      mass action of the two acceptor substrates present. Enzymatic synthesis of 2
      deoxy-beta-D-glucosyl-(1->4)-D-glucose is effectively promoted by catalytic
      concentrations of phosphate, suggesting that catalytic reaction proceeds through
      a quaternary complex of CuCPase, D-glucal, phosphate, and D-glucose. Conversion
      of D-glucal and phosphate presents a convenient single-step synthesis of 2-deoxy
      alpha-D-glucose 1-phosphate that is difficult to prepare chemically.

PMID- 22591556
TI  - Structural studies of the O-polysaccharide of Pragia fontium 97U124 containing 2
      acetamido-2,4,6-trideoxy-4-(D-glyceroyl)amino-D-glucose.
AB  - The O-polysaccharide was obtained by acid hydrolysis of the lipopolysaccharide of
      Pragia fontium 97U124 and studied by sugar analysis and 1D and 2D NMR
      spectroscopy. A new bacillosamine derivative, 2-acetamido-2,4,6-trideoxy-4-(D
      glyceroyl)amino-D-glucose (D-QuiNAc4NAcyl), was identified as a polysaccharide
      constituent. The following structure of the O-polysaccharide was established ->3)
      alpha-L-FucpNAc-(1->3)-alpha-L-FucpNAc-(1->3)-beta-D-QuipNAc4NAcyl-(1-> This
      structure is closely related to that of the D-QuiNAc4NAc-containing O
      polysaccharide of Pseudomonas aurantiaca IMV 31 established earlier (Knirel, Y.
      A.; Zdorovenko, G. M.; Veremeychenko, S. N.; Lipkind, G. M.; Shashkov, A. S.;
      Zakharova, I. Y.; Kochetkov, N. K. Bioorg. Khim.1988, 14, 352-358).

PMID- 22591557
TI  - A late recurring and easily forgotten tumor: ovarian granulosa cell tumor.
AB  - Ovarian granulosa cell tumor (GCT) is a malignant tumor with slow progression.
      The recurrence of granulosa cell tumor often happens after 5 years, leading to a
      'forgotten tumor' by the patient. We present the case of a 64-year-old woman with
      a presentation of left flank pain. An initial computed tomography scan revealed a
      single tumor with multiple adjacent organ invasions. Surgical intervention was
      prescribed and the pathological results revealed a metastatic granulosa cell
      tumor. We also review the literature for the follow-up and further management of
      this tumor.

PMID- 22591558
TI  - Altered manganese homeostasis: implications for BLI-3-dependent dopaminergic
      neurodegeneration and SKN-1 protection in C. elegans.
AB  - The role of environmental factors in the etiology of neurodegenerative disorders,
      such as in Parkinson's disease (PD), has become increasingly imperative for
      examination, as genetics can only partially account for most cases. The heavy
      metal manganese (Mn) falls into this category of environmental contributors, as
      it is both essential but also neurotoxic upon overexposure and produces
      Parkinsonian symptomatology. In order to understand its toxicity, this review
      focuses on the various aspects of improper Mn homeostasis and its consequences
      using the genetically amenable Caenorhabditis elegans model. Namely, the roles of
      Mn transporter homologs for the divalent metal transporter 1 (DMT1) will be
      discussed, as Mn homeostasis is initially governed by proper cellular transport.
      Mn dyshomeostasis can result in enhanced oxidative stress through synergistic
      actions of dopamine oxidation that is dependent on the C. elegans dual oxidase
      BLI-3. Finally, neuroprotection conferred by the antioxidant transcription factor
      Nrf2 (C. elegans SKN-1) may signify a potential therapeutic approach against Mn
      toxicity.

PMID- 22591559
TI  - Selective salpingography: preliminary experience of an office operative option
      for proximal tubal recanalization.
AB  - OBJECTIVE: To evaluate treatment efficacy and patient acceptability of the new
      Radiographic Tubal Assessment Set (RTAS) (Cook Ireland Ltd., Limerick, Ireland)
      for selective salpingography (SSG). STUDY DESIGN: 33 women, between 23 and 38
      years old, referred to the Fertility Centre of the Department of Obstetrics,
      Gynecology and Reproductive Science, Second University of Naples, for sterility
      problems, underwent an office operative SSG with the RTAS. Of the 33 women, 12
      had bilateral tubal obstruction (Group A) and 21 had unilateral tubal obstruction
      (Group B). Patients who did not regain tubal patency were referred for
      laparoscopic surgery. To verify patient acceptability, a visual analogue score
      (VAS 1-10) of pain was completed immediately after the procedure. RESULTS: From a
      total of 45 obstructed fallopian tubes, 34 were recanalized, giving a success
      rate for the procedure of 75.6% (p<0.001). Nine patients with bilateral tubal
      obstruction (Group A) had the tubes recanalized and five obtained a spontaneous
      pregnancy. Sixteen patients with monolateral tubal obstruction (Group B) had the
      tubes recanalized and nine obtained a spontaneous pregnancy. A total of seven
      patients were sent for operative laparoscopy: four of them had the tubes
      recanalized and two obtained a spontaneous pregnancy. One patient was lost to
      follow-up. The evaluation of the level of pain felt during the procedure on the
      10 cm VAS showed mean pelvic pain 2.9 +/- 2.2, and an incidence of no
      discomfort+/-low pain significantly higher than moderate+/-severe pain
      (p<0.0001). CONCLUSION: The RTAS can be considered a safe and effective tool to
      perform this office operative procedure for tubal recanalization, with a high
      acceptability for the patient. The "see and treat" approach in patients with
      proximal tubal obstruction (PTO) suggests for the future the use of this device
      under sonographic guidance, taking into account accurate patient selection.

PMID- 22591560
TI  - Advantages of a high-throughput measure of hair fiber torsional properties.
AB  - While the tensile response of fibers of human hair is the most extensively
      studied mode of mechanical deformation, the properties of hair in different
      deformation modes remain of interest and can provide valuable insight into the
      effects of chemical treatments. Previously reported methods for the measurement
      of fibers in torsional deformation have inherent systematic errors, are low
      throughput, and are operator-intensive. This paper presents a new method for the
      measurement of fiber torsional properties developed to reduce these errors and to
      improve the efficiency of the technique. This method was designed to be fully
      automated, requiring no operator input during an experiment, and affording higher
      sample throughput while improving the ease of use in variable climatic
      conditions. The new method is compared to a conventional torsional pendulum
      method for measuring fiber shear modulus, and an evaluation of experimental
      reproducibility is made using hair and nylon fibers. It was found that the new
      method provides absolute values for shear modulus similar to those of the
      pendulum technique, with reduced run-to-run variability between fibers, while
      enabling larger sample numbers to be explored in shorter times.

PMID- 22591561
TI  - Natural oils and waxes: studies on stick bases.
AB  - The objective of the present article was to examine the role of origin and
      quantity of selected natural oils and waxes in the determination of the thermal
      properties and hardness of stick bases. The natural oils and waxes selected for
      the study were sunflower, castor, jojoba, and coconut oils. The selected waxes
      were yellow beeswax, candelilla wax, and carnauba wax. The hardness of the
      formulations is a critical parameter from the aspect of their application.
      Hardness was characterized by the measurement of compression strength along with
      the softening point, the drop point, and differential scanning calorimetry (DSC).
      It can be concluded that coconut oil, jojoba oil, and carnauba wax have the
      greatest influence on the thermal parameters of stick bases.

PMID- 22591562
TI  - Simultaneous analysis and monitoring of 16 UV filters in cosmetics by high
      performance liquid chromatography.
AB  - Sixteen UV filters were simultaneously analyzed using the high-performance liquid
      chromatographic method. They were drometrizole (USAN Drometrizole), 4
      methylbenzylidene camphor (USAN Enzacamene), menthyl anthranilate (USAN Menthyl
      anthranilate), benzophenone-3 (USAN Oxybenzone), benzophenone-8 (USAN
      Dioxybenzone), butyl methoxydibenzoylmethane (USAN Avobenzone), ethylhexyl
      triazone (USAN Octyl triazone), octocrylene (USAN Octocrylene), ethylhexyl
      dimethyl p-aminobenzoic acid (USAN Padimate O), ethylhexyl methoxycinnamate (USAN
      Octinoxate), p-aminobenzoic acid (USAN Aminobenzoic acid), 2-phenylbenzimidazole
      5-sulfonic acid (USAN Ensulizole), isoamyl p-methoxycinnamate (USAN Amiloxate),
      and recent UV filters such as diethylhexyl butamidotriazone (USAN Iscotrizinol),
      methylene bis-benzotriazolyl tetramethylbutylphenol (USAN Bisoctrizole), and
      terephthalylidene dicamphor sulfonic acid (USAN Ecamsule). Separation of the UV
      filters was carried out in a C(18) column with a gradient of methanol-phosphate
      buffer, and the UV detection was at 300, 320, or 360 nm without any interference.
      The limits of detection were between 0.08 and 1.94 MUg/ml, and the limits of
      quantitation were between 0.24 and 5.89 MUg/ml. The extracting solvent for the UV
      filters was methanol, except for ethylhexyl triazone and methylene bis
      benzotriazolyl tetramethylbutylphenol, which were prepared with tetrahydrofuran.
      The recoveries from spiked samples were between 94.90% and 116.54%, depending on
      the matrixes used. The developed method was applied to 23 sunscreens obtained
      from local markets, and the results were acceptable to their own criteria and to
      maximum authorized concentrations. Consequently, these results would provide a
      simple extracting method and a simultaneous determination for various UV filters,
      which can improve the quality control process as well as the environmental
      monitoring of sunscreens.

PMID- 22591563
TI  - Development of photochemoprotective herbs containing cosmetic formulations for
      improving skin properties.
AB  - Botanical photochemoprotectives are used because they act on various stages to
      prevent skin cancer and photoaging. The aim of this study was to prepare herbal
      creams from various photochemoprotective herbs and to perform efficacy studies on
      them by using physicochemical, microbiological, safety, psychometric,
      biophysical, and sun protection factor measurements. Herbal creams were prepared
      by incorporating hydroalcoholic extracts of Curcuma caesia (rhizome), Areca
      catechu (seeds), Centella asiatica (leaves) Cinnamon zeylanicum (dried bark), and
      Tamarindus indica (fruit pulp) in varied concentrations (1-5% w/w) in a base
      cream. The efficacy of all formulations was checked out for four weeks on 60
      normal subjects on the volar forearm for evaluation of biophysical properties,
      and for psychometric evaluations (fragrance, lathery feel, softness, irritation,
      stickiness, smoothness, and aftereffect on the skin) and safety measurements. In
      the biophysical characterization, a cutometer for viscoelasticity, a mexameter
      for melanin content, a corneometer for hydration, and a sebumeter for sebum
      determination were used. All the cream formulations with 1% and 3% w/w extracts
      showed positive results and passed physicochemical, microbiological, and safety
      tests. The SPF values increased as the concentration of extract was increased up
      to a limit in the formulations. The SPF values were significantly higher (p <
      0.01) in formulations with 3% herbal extract than with 1% herbal extract.
      Increased skin hydration, sebum levels, viscoelasticity, and decreased melanin
      values were obtained. The Cinnamon, Centella, and Tamarindus formulations were
      found more effective as photoprotectives than the Areca and Curcuma formulations.

PMID- 22591564
TI  - UVc-irradiation sublethal stress does not alter antibiotic susceptibility of
      staphylococci (MRSA, MSSA, and coagulase-negative staphylococci) to beta-lactam,
      macrolide, and fluoroquinolone antibiotic agents.
AB  - Skin tanning, either by exposure to natural sunlight or through use of UV
      sunbeds, has become a popular practice in the US, where it is estimated that
      approximately 1 million times per day someone in the US uses UV radiation for
      skin tanning, equating to 30 million Americans (circa 10% of the US population)
      who use a tanning bed. As well as exposing the host to periods of UV radiation,
      such practices also expose commensal skin bacteria, including Staphylococcus
      aureus, to such UV radiation. Previous work has indicated that environmental
      stresses on bacteria may lead to an upregulation of stress responses, in an
      attempt for the organism to combat the applied stress and remain viable. UV light
      may act as an environmental stress on bacteria, and so it was the aim of this
      study to examine the effect of UVc light on the antibiotic susceptibility of
      commensal skin bacteria, to determine if UV radiation would increase the
      antibiotic resistance of such skin flora and thus lead to a potential skin flora
      with increased antibiotic resistance. Previously, it has been shown that UVc
      light has a greater mutational effect on bacteria compared to lower-energy UV
      forms, including UVa and UVb light. Therefore, we decided to employ UVc light in
      our study to amplify the potential for mutational events occurring in skin
      staphylococci organisms (n=8) including methicillin-sensitive Staphylococcus
      aureus (n=2), methicillin-resistant Staphylococcus aureus (n=4), and coagulase
      negative staphylococci (Staphylococcus haemolyticus) (n=2) were exposed to
      varying degrees of sublethal radiation via UVc light, and their minimum
      inhibitory concentration (MIC) susceptibility was determined by broth dilution
      assay against three classes of commonly used antibiotics, namely beta-lactams
      (penicillin), macrolides (erythromycin), and fluoroquinolones (ciprofloxacin).
      There was no significant difference between antibiotic susceptibility before UVc
      exposure and until maximum sublethal stress, prior to cell death due to fatal UVc
      exposure with the cells. These results indicate that UV environmental
      stress/exposure does not upregulate antibiotic resistance, and therefore these
      data indicate that UVc radiation does not lead to a more antibiotic-resistant
      population in the staphylococci organisms post-exposure.

PMID- 22591567
TI  - Extracorporeal membrane oxygenation-assisted primary percutaneous coronary
      intervention may improve survival of patients with acute myocardial infarction
      complicated by profound cardiogenic shock.
AB  - PURPOSE: The aim of this study was to evaluate the impact of extracorporeal
      membrane oxygenation (ECMO) assistance on the clinical outcome of patients with
      acute myocardial infarction (AMI) that is complicated by profound cardiogenic
      shock (CS) who received primary percutaneous coronary intervention (PCI).
      MATERIALS AND METHODS: We collected patients from January 2004 through December
      2006 (stage 1); 25 patients who presented with AMI and received primary PCI and
      had profound CS were enrolled in the study. Intraaortic balloon counterpulsation
      (IABP) was the only modality for extracorporeal support in our hospital. From
      January 2007 through December 2009 (stage 2), 33 patients who presented with AMI
      and received primary PCI and had profound CS were enrolled; for this stage; both
      intra-aortic balloon counter-pulsation and ECMO support were available in our
      facility. RESULTS: A Kaplan-Meier survival analysis displayed significantly
      improved survival for patients in stage 2 (P = .001; 1-year survival in stage 1
      vs 2; 24% vs 63.64%). Patients presenting with either STEMI (ST segment elevation
      myocardial infarction) or NSTEMI (Non-ST segment elevation myocardial infarction)
      benefited from ECMO-assisted PCI (P < .05). In stage 1, patients with refractory
      ventricular tachycardia/ventricular fibrillation had a very low survival rate;
      however, in stage 2, the survival rate of patients with and without refractory
      ventricular tachycardia/ventricular fibrillation was similar (P = .316).
      CONCLUSION: Extracorporeal membrane oxygenation-assisted PCI for patients with
      AMI that is complicated by profound CS may improve the 30-day and 1-year survival
      rates.

PMID- 22591568
TI  - Influence of full-time intensivist and the nurse-to-patient ratio on the
      implementation of severe sepsis bundles in Korean intensive care units.
AB  - PURPOSE: The reported actual compliance for severe sepsis bundles was very low,
      suggesting the presence of barriers to their implementation. The purpose of this
      study was to assess the influence of full-time intensivist and nurse-to-patient
      ratio in Korean intensive care units (ICUs) on the implementation of the severe
      sepsis bundles and clinical outcome. MATERIALS AND METHODS: A total of 251
      patients with severe sepsis were enrolled from 28 adult ICUs during the July,
      2009. We recorded the organizational characteristics of ICUs, patients'
      characteristics and clinical outcomes, and the compliance for severe sepsis
      bundles. RESULTS: Complete compliance with the resuscitation bundle and totally
      complete compliance with all element targets for resuscitation and management
      bundles were significantly higher in the ICU with full-time intensivist and a
      nurse-to-patient ratio of 1:2 (P < .05). The hazard ratio (HR) for hospital
      mortality was independently reduced by the presence of full-time intensivist (HR,
      0.456; 95% confidence interval, 0.223-0.932), and a nurse-to-patient ratio of 1:2
      was independently associated with a lower 28-day mortality (HR, 0.459; 95%
      confidence interval, 0.211-0.998). CONCLUSIONS: The full-time intensivist and the
      nurse-to-patient ratio had a substantial influence on the implementation of
      severe sepsis bundles and the mortalities of patients with severe sepsis.

PMID- 22591569
TI  - Discordance between microcirculatory alterations and arterial pressure in
      patients with hemodynamic instability.
AB  - PURPOSE: Recent studies reported that microcirculatory blood flow alterations
      occur in patients with circulatory shock independent of arterial pressure but
      typically lack baseline microcirculatory data before the insult and after
      recovery. We selected cardiopulmonary bypass (CPB) patients with expected and
      rapidly reversible hemodynamic instability to test the hypothesis that
      microcirculatory alterations can occur independent of mean arterial pressure
      (MAP). METHODS: Prospective observational study using sidestream darkfield
      videomicroscopy to measure sublingual microcirculatory flow preoperative (PRE),
      postoperatively after CPB (POST), and after recovery (REC). We determined the
      microcirculatory flow index (MFI) at each time point, blinded to all clinical
      data and compared change in MFI and MAP across time points using analysis of
      variance adjusted for multiple comparisons. RESULTS: We enrolled 20 subjects, 17
      of 20 required inotrope/vasopressor agents at CPB discontinuation, 7 of 20 were
      on inotrope/vasopressor agents at the time of imaging, 20 of 20 were receiving
      continuous nitroglycerin. We observed an increase in post-CPB MFI (PRE, 2.16 +/-
      0.29; POST, 2.45 +/- 0.62; REC, 2.26 +/- 0.25; P < .01) without a concomitant
      increase in MAP. CONCLUSION: In this cohort of patients with hemodynamic
      instability, we observed discordance between microcirculatory blood flow and
      arterial pressure. These data support the concept that microcirculatory blood
      flow indices can yield physiologic information distinct from macrocirculatory
      hemodynamic parameters.

PMID- 22591570
TI  - African American race, obesity, and blood product transfusion are risk factors
      for acute kidney injury in critically ill trauma patients.
AB  - PURPOSE: Acute kidney injury (AKI) is a common source of morbidity after trauma.
      We sought to determine novel risk factors for AKI, by Acute Kidney Injury Network
      (AKIN) criteria, in critically ill trauma patients. MATERIALS AND METHODS: A
      prospective cohort of 400 patients admitted to the intensive care unit of a level
      1 trauma center was followed for the development of AKI over 5 days. RESULTS:
      Acute kidney injury developed in 147 (36.8%) of 400 patients. In multivariable
      regression analysis, independent risk factors for AKI included African American
      race (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.08-3.18; P = .024),
      body mass index of 30 kg/m(2) or greater (OR, 4.72 versus normal body mass index;
      95% CI, 2.59-8.61; P < .001), diabetes mellitus (OR, 3.26; 95% CI, 1.30-8.20; P =
      .012), abdominal Abbreviated Injury Scale score of 4 or more (OR, 3.78; 95% CI,
      1.79-7.96; P < .001), and unmatched packed red blood cells administered during
      resuscitation (OR, 1.13 per unit; 95% CI, 1.04-1.23; P = .004). Acute Kidney
      Injury Network stages 1, 2, and 3 were associated with hospital mortality rates
      of 9.8%, 13.7%, and 30.4%, respectively, compared with 3.8% for those without AKI
      (P < .001). CONCLUSIONS: Acute kidney injury in critically ill trauma patients is
      associated with substantial mortality. The findings of African American race,
      obesity, and blood product administration as independent risk factors for AKI
      deserve further study to elucidate underlying mechanisms.

PMID- 22591571
TI  - Extravascular lung water indexed or not to predicted body weight is a predictor
      of mortality in septic shock patients.
AB  - PURPOSE: The purpose was to investigate whether extravascular lung water (EVLW)
      indexed to actual body weight (EVLWa) is an independent predictor of mortality in
      patients with septic shock, to determine the relationship between EVLWa and other
      markers of lung injury, and to test if indexing EVLW with predicted body weight
      (EVLWp) strengthens its predictive power. METHODS: Extravascular lung water,
      pulmonary vascular permeability index, and other markers of lung injury were
      measured prospectively in 55 patients with septic shock for 3 days. RESULTS: At
      day 1, EVLWa, EVLWp, and pulmonary vascular permeability index were not
      significantly different between survivors and nonsurvivors. However, in parallel
      to the course of septic shock, these variables decreased only in the survivors
      and remained elevated in the nonsurvivors, reaching intergroup difference by day
      3. In multiple logistic regression analysis, both EVLWa and EVLWp (at day 3) were
      predictors of mortality with an odds ratio of 2 (95% confidence interval, 1.12
      3.7) and 1.7 (95% confidence interval, 1.1-2.5) per SD increase, respectively.
      The receiver operating characteristic curve analysis showed that EVLWp did not
      improve the discriminative power of EVLW to predict mortality. Extravascular lung
      water indexed to actual body weight correlated with lung injury score and with
      the ratio of arterial oxygen partial pressure to inspired oxygen fraction but not
      with static respiratory compliance. Indexing EVLW to predicted body weight did
      not ameliorate these correlations. CONCLUSIONS: Extravascular lung water indexed
      or not to predicted body weight is an independent predictor of mortality in
      patients with septic shock. Repeated measurements of EVLW indexes over time,
      rather than a too-early measurement, seem to be more appropriate for predicting
      outcome.

PMID- 22591572
TI  - Prognostic models based on administrative data alone inadequately predict the
      survival outcomes for critically ill patients at 180 days post-hospital
      discharge.
AB  - There is interest in evaluating the quality of critical care by auditing patient
      outcomes after hospital discharge. Risk adjustment using acuity of illness
      scores, such as Acute Physiology and Chronic Health Evaluation (APACHE III)
      scores, derived from clinical databases is commonly performed for in-hospital
      mortality outcome measures. However, these clinical databases do not routinely
      track patient outcomes after hospital discharge. Linkage of clinical databases to
      administrative data sets that maintain records on patient survival after
      discharge can allow for the measurement of survival outcomes of critical care
      patients after hospital discharge while using validated risk adjustment methods.
      OBJECTIVE: The aim of this study was to compare the ability of 4 methods of risk
      adjustment to predict survival of critically ill patients at 180 days after
      hospital discharge: one using only variables from an administrative data set, one
      using only variables from a clinical database, a model using a full range of
      administrative and clinical variables, and a model using administrative variables
      plus APACHE III scores. DESIGN: This was a population-based cohort study.
      PATIENTS: The study sample consisted of adult (>15 years of age) residents of
      Victoria, Australia, admitted to a public hospital intensive care unit between 1
      January 2001 and 31 December 2006 (n = 47,312 linked cases). Logistic regression
      analyses were used to develop the models. RESULTS: The administrative-only model
      was the poorest predictor of mortality at 180 days after hospital discharge (C =
      0.73). The clinical model had substantially better predictive capabilities (C =
      0.82), whereas the full-linked model achieved similar performance (C = 0.83).
      Adding APACHE III scores to the administrative model also had reasonable
      predictive capabilities (C = 0.83). CONCLUSIONS: The addition of APACHE III
      scores to administrative data substantially improved model performance to the
      level of the clinical model. Although linking data systems requires some
      investment, having the ability to evaluate case ascertainment and accurately risk
      adjust outcomes of intensive care patients after discharge will add valuable
      insights into clinical audit and decision-making processes.

PMID- 22591573
TI  - Hypophosphatemia and its clinical implications in critically ill children: a
      retrospective study.
AB  - PURPOSE: The aims of this study were to determine the prevalence of
      hypophosphatemia and to discuss the clinical implications of hypophosphatemia in
      critically ill children. MATERIALS AND METHODS: A retrospective review of the
      medical records of children admitted to the pediatric intensive care unit from
      December 2006 to December 2007 was conducted. RESULTS: In 60.2% (n = 71) of the
      patients, any serum phosphorous level at admission and at the third day or
      seventh day after admission to pediatric intensive care unit was in
      hypophosphatemic range. Sepsis was present in 22.9% (n = 27) of the children
      studied and was associated with hypophosphatemia (P = .02). Hypophosphatemia was
      also associated with use of furosemide (P = .04), use of steroid (P = .04), use
      of beta(2) agonist (P = .026), and use of an H(2) blocker (P = .004). There was a
      significant association between hypophosphatemia and the rate to attain target
      caloric requirements by enteral route (P = .007). The median time to attain
      target caloric requirements by enteral route was 2.9 +/- 1.9 (0.2-10) days in the
      normophosphatemic group and 4.4 +/- 2.8 (0.3-12) days in the hypophosphatemic
      group. In the multiple regression model, solely the rate to attain the target
      caloric requirements by enteral route demonstrated independent association with
      hypophosphatemia (P = .006; beta = .27; 95% confidence interval, 0.02-0.09).
      Significant association was found between hypophosphatemia and the duration of
      mechanical ventilation and between hypophosphatemia and pediatric intensive care
      unit length of stay (P = .02 and P = .001, respectively). CONCLUSIONS: Critically
      ill pediatric patients are prone to hypophosphatemia, especially if they cannot
      be fed early by enteral route. Hypophosphatemia is associated with an increased
      duration of mechanical ventilation and increased length of stay in the pediatric
      intensive care unit, suggesting that active repletion might improve these
      parameters.

PMID- 22591574
TI  - Quantitative evaluation of noncovalent interactions between glyphosate and
      dissolved humic substances by NMR spectroscopy.
AB  - Interactions of glyphosate (N-phosphonomethylglycine) herbicide (GLY) with
      soluble fulvic acids (FAs) and humic acids (HAs) at pH 5.2 and 7 were studied by
      (1)H and (31)P NMR spectroscopy. Increasing concentrations of soluble humic
      matter determined broadening and chemical shift drifts of proton and phosphorus
      GLY signals, thereby indicating the occurrence of weak interactions between GLY
      and humic superstructures. Binding was larger for FAs and pH 5.2 than for HAs and
      pH 7, thus suggesting formation of hydrogen bonds between GLY carboxyl and
      phosphonate groups and protonated oxygen functions in humic matter. Changes in
      relaxation and correlation times of (1)H and (31)P signals and saturation
      transfer difference NMR experiments confirmed the noncovalent nature of GLY-humic
      interactions. Diffusion-ordered NMR spectra allowed calculation of the glyphosate
      fraction bound to humic superstructures and association constants (K(a)) and
      Gibbs free energies of transfer for GLY-humic complex formation at both pH
      values. These values showed that noncovalent interactions occurred most
      effectively with FAs and at pH 5.2. Our findings indicated that glyphosate may
      spontaneously and significantly bind to soluble humic matter by noncovalent
      interactions at slightly acidic pH and, thus, potentially pollute natural water
      bodies by moving through soil profiles in complexes with dissolved humus.

PMID- 22591576
TI  - Loci nominally associated with autism from genome-wide analysis show enrichment
      of brain expression quantitative trait loci but not lymphoblastoid cell line
      expression quantitative trait loci.
AB  - BACKGROUND: Autism spectrum disorder is a severe early onset neurodevelopmental
      disorder with high heritability but significant heterogeneity. Traditional genome
      wide approaches to test for an association of common variants with autism
      susceptibility risk have met with limited success. However, novel methods to
      identify moderate risk alleles in attainable sample sizes are now gaining
      momentum. METHODS: In this study, we utilized publically available genome-wide
      association study data from the Autism Genome Project and annotated the results
      (P <0.001) for expression quantitative trait loci present in the parietal lobe
      (GSE35977), cerebellum (GSE35974) and lymphoblastoid cell lines (GSE7761). We
      then performed a test of enrichment by comparing these results to simulated data
      conditioned on minor allele frequency to generate an empirical P-value indicating
      statistically significant enrichment of expression quantitative trait loci in top
      results from the autism genome-wide association study. RESULTS: Our findings show
      a global enrichment of brain expression quantitative trait loci, but not
      lymphoblastoid cell line expression quantitative trait loci, among top single
      nucleotide polymorphisms from an autism genome-wide association study.
      Additionally, the data implicates individual genes SLC25A12, PANX1 and PANX2 as
      well as pathways previously implicated in autism. CONCLUSIONS: These findings
      provide supportive rationale for the use of annotation-based approaches to genome
      wide association studies.

PMID- 22591575
TI  - Laser speckle flowmetry method for measuring spatial and temporal hemodynamic
      alterations throughout large microvascular networks.
AB  - OBJECTIVES: 1) To develop and validate laser speckle flowmetry (LSF) as a
      quantitative tool for individual microvessel hemodynamics in large networks. 2)
      To use LSF to determine if structural differences in the dorsal skinfold
      microcirculation (DSFWC) of C57BL/6 and BALB/c mice impart differential network
      hemodynamic responses to occlusion. METHODS: We compared LSF velocity
      measurements with known/measured velocities in vitro using capillary tube tissue
      phantoms and in vivo using mouse DSFWCs and cremaster muscles. Hemodynamic
      changes induced by feed arteriole occlusion were measured using LSF in DSFWCs
      implanted on C57BL/6 and BALB/c mice. RESULTS: In vitro, we found that the
      normalized speckle intensity (NSI) versus velocity linear relationship (R(2) >=
      0.97) did not vary with diameter or hematocrit and can be shifted to meet an
      expected operating range. In vivo, DSFWC and cremaster muscle preparations (R(2)
      = 0.92 and 0.95, respectively) demonstrated similar linear relationships between
      NSI and centerline velocity. Stratification of arterioles into predicted
      collateral pathways revealed significant differences between C57BL/6 and BALB/c
      strains in response to feed arteriole occlusion. CONCLUSIONS: These data
      demonstrate the applicability of LSF to intravital microscopy microcirculation
      preparations for determining both relative and absolute hemodynamics on a network
      wide scale while maintaining the resolution of individual microvessels.

PMID- 22591577
TI  - Changes in brain glucose metabolism in subthalamic nucleus deep brain stimulation
      for advanced Parkinson's disease.
AB  - BACKGROUND: Despite its large clinical application, our understanding about the
      mechanisms of action of deep brain stimulation of the subthalamic nucleus is
      still limited. Aim of the present study was to explore cortical and subcortical
      metabolic modulations measured by Positron Emission Tomography associated with
      improved motor manifestations after deep brain stimulation in Parkinson disease,
      comparing the ON and OFF conditions. PATIENTS AND METHODS: Investigations were
      performed in the stimulator off- and on-conditions in 14 parkinsonian patients
      and results were compared with a group of matched healthy controls. The results
      were also used to correlate metabolic changes with the clinical effectiveness of
      the procedure. RESULTS: The comparisons using Statistical parametric mapping
      revealed a brain metabolic pattern typical of advanced Parkinson disease. The
      direct comparison in ON vs OFF condition showed mainly an increased metabolism in
      subthalamic regions, corresponding to the deep brain stimulation site. A positive
      correlation exists between neurostimulation clinical effectiveness and metabolic
      differences in ON and OFF state, including the primary sensorimotor, premotor and
      parietal cortices, anterior cingulate cortex. CONCLUSION: Deep brain stimulation
      seems to operate modulating the neuronal network rather than merely exciting or
      inhibiting basal ganglia nuclei. Correlations with Parkinson Disease cardinal
      features suggest that the improvement of specific motor signs associated with
      deep brain stimulation might be explained by the functional modulation, not only
      in the target region, but also in surrounding and remote connecting areas,
      resulting in clinically beneficial effects.

PMID- 22591578
TI  - Amplitude fluctuations in essential tremor.
AB  - OBJECTIVE: To assess temporal amplitude variability in patients with essential
      tremor (ET). METHODS: Patients who satisfied the diagnostic criteria for probable
      or definite ET were enrolled in the study. Each enrolled patient was first rated
      using the essential tremor rating assessment scale (TETRAS). Postural and kinetic
      tremors of the arms were then measured using a quantitative motor assessment
      system (QMAS) starting at 8:00 AM (T0-baseline) every 2 h for 6 h. Subjects were
      videotaped performing the tasks. Single subjects consecutively performed each
      assessment twice during every time-interval. At the end of the study, videos were
      randomized and blindly rated using TETRAS. RESULTS: Twelve ET subjects were
      enrolled. QMAS and video scores were directly correlated with high test-retest
      reliability for each time-interval. Furthermore, the QMAS scores at T0
      significantly correlated with in-person rated TETRAS scores as well as with
      subsequent time-intervals instrumental scores. No significant differences were
      detected between time-intervals QMAS average measurements using ANOVA. There was
      a maximal 23% absolute variation in tremor amplitude from baseline as determined
      by the QMAS. Test for equality of variance showed high measurement variability
      for subjects with high QMAS scores at T0 and throughout the 6 h of assessment.
      CONCLUSIONS: Baseline measures are predictive of tremor amplitude at subsequent
      assessments during the day. High amplitude tremor is associated with high intra
      assessment variability.

PMID- 22591579
TI  - Do we provide meaningful guidance for healthful eating? An investigation into
      consumers' interpretation of frequency consumption terms.
AB  - OBJECTIVE: To investigate consumers' understanding of terms commonly used to
      provide guidance about frequency and quantity of food consumption. METHODS: A
      survey of 405 shoppers explored how frequently consumers thought food labeled
      with the terms "eat often," "eat moderately," "eat occasionally," "a sometimes
      food," and "an extra food" should be eaten. In a separate phase, 30 grocery
      buyers responded to open-ended questions about their interpretation of these
      terms. RESULTS: Responses indicated significant differences in meaning between
      the terms. However, the specific interpretation of each term varied considerably
      across respondents. The qualitative research found the terms to be highly
      subjective, and there was a high degree of uncertainty about the meaning of the
      term "an extra food" in particular. CONCLUSIONS AND IMPLICATIONS: Food frequency
      and descriptive terms currently used do not provide meaningful or consistent
      nutritional guidance. There is a need for simple, unambiguous terminology.

PMID- 22591581
TI  - Results from the 2009 Michigan farm to school survey: participation grows from
      2004.
AB  - OBJECTIVE: This study investigated changes in Michigan school food service
      directors' farm to school (FTS) participation levels and perspectives since a
      2004 survey and factors that would facilitate FTS expansion. DESIGN: Electronic
      survey census of all Michigan school food service directors. SETTING: Michigan
      kindergarten-12th grade schools. PARTICIPANTS: Food service directors of National
      School Lunch programs in Michigan. VARIABLES MEASURED: Survey respondents were
      asked about local food purchasing behaviors, interests, motivations, concerns,
      and barriers. ANALYSIS: Data were analyzed through descriptive statistics.
      Wilcoxon signed rank tests were calculated to compare 2004 and 2009 results.
      RESULTS: Participation in FTS was more than 3 times higher (41.5%) than in 2004
      (10.6%), and the vast majority of school districts (77.0%) had taken at least 1
      step to connect students with local food. Budget and cost issues were ranked
      higher as barriers to FTS than in 2004, but the desire to help Michigan farms had
      also substantially increased. Fresh and whole produce items were generally
      preferred for local procurement over frozen or canned items. CONCLUSIONS AND
      IMPLICATIONS: Education to reverse perceived limits of procurement regulations,
      food safety assurances, and strategies to mitigate tight school food budgets are
      needed to encourage FTS expansion.

PMID- 22591580
TI  - Examining multiple parenting behaviors on young children's dietary fat
      consumption.
AB  - OBJECTIVE: To understand the association between parenting and children's dietary
      fat consumption, this study tested a comprehensive model of parenting that
      included parent household rules, parent modeling of rules, parent mediated
      behaviors, and parent support. DESIGN: Cross-sectional. SETTING: Baseline data
      from the MOVE/me Muevo project, a recreation site-based obesity prevention and
      control intervention trial. PARTICIPANTS: Five hundred forty-one parents of
      children between the ages of 5 and 8 years and living in San Diego County. MAIN
      OUTCOME MEASURE: Children's fat consumption based on parent report using a short
      food frequency questionnaire. ANALYSIS: A hierarchical linear regression was
      conducted. In exploratory analyses, a stepwise backward elimination approach was
      used. RESULTS: Children's fat consumption was positively associated with parent
      household rules (P < .01) and negatively associated with parent modeling of rules
      (P < .01). CONCLUSIONS AND IMPLICATIONS: Controlling parenting behaviors, such as
      rule setting, are associated with more frequent fat consumption, whereas role
      modeling healthful behaviors is associated with less frequent fat consumption.
      Changing parenting behaviors with regard to how they feed their children is a
      logical avenue for improving eating behaviors.

PMID- 22591583
TI  - Screening of genes related to sulfide metabolism in Urechis unicinctus (Echiura,
      Urechidae) using suppression subtractive hybridization and cDNA microarray
      analysis.
AB  - Exogenous sulfide can generally induce metabolic injuries in most organisms and
      even cause death. However, organisms inhabiting intertidal zones, hydrothermal
      vents, and cold seeps, can tolerate, metabolize, and utilize sulfide. In this
      study, both suppression subtractive hybridization and cDNA microarray analysis
      were employed to screen sulfide metabolism-related genes from the body wall in
      echiuran worm Urechis unicinctus, a marine sediment species. A total of 3456
      monoclones were isolated and 82 were identified as differentially expressed genes
      in worms exposed to 50 MUM sulfide for 24 h, compared to controls. The identified
      genes encoded proteins with multiple processes, including metabolism, cellular
      process, biological regulation, response to stimulus, multicellular organismal
      process, localization, development, and cellular component organization. Eight
      genes, serase, vacuolar protein, src tyrosine kinase, sulfide oxidase-like
      oxidoreductase, aprataxin, SN-RNP, aminopeptidase, and predicted protein, were
      selected to verify expression in the worm using qRT-PCR. The agreement of gene
      expression evaluation was 62.5% between the results of microarray analysis and
      qRT-PCR. These new data will provide clues for further probing of the molecular
      mechanism of sulfide metabolism.

PMID- 22591582
TI  - Decrease in television viewing predicts lower body mass index at 1-year follow-up
      in adolescents, but not adults.
AB  - OBJECTIVE: To examine associations between television viewing, sugar-sweetened
      beverage consumption, eating out, physical activity, and body weight change over
      1 year. DESIGN: Secondary data analysis from randomized intervention trial.
      SETTING: Households in the community. PARTICIPANTS: Adults (n = 153) and
      adolescents (n = 72) from the same households. INTERVENTION: Households were
      randomized to a home-based obesity prevention intervention or to a no
      intervention control group for a 1-year period. MAIN OUTCOME MEASURES: Self
      reported television viewing (TV) hours, diet, and physical activity. Body mass
      index (BMI) computed from measured weight and height (primary outcome measure).
      ANALYSIS: Mixed-model regression. RESULTS: Among adolescents, a significant
      prospective association was observed between decreases in television viewing
      hours and lower BMI z score at 1-year follow-up (decreased TV hours: BMI z score
      mean = 0.65; no change or increase TV hours: BMI z score = 0.92; P < .02). No
      significant prospective associations were observed among adults. CONCLUSIONS AND
      IMPLICATIONS: Reducing television viewing may be an effective strategy to prevent
      excess weight gain among adolescents.

PMID- 22591584
TI  - Correlates of agitation and depression in nursing home residents with dementia.
AB  - BACKGROUND: The purpose of this study was to investigate the relationship between
      dementia severity, age, gender, and prescription of psychotropics, and syndromes
      of agitation and depression in a sample of nursing home residents with dementia.
      METHODS: The Cohen-Mansfield Agitation Inventory (CMAI) was administered to
      residents with dementia (N = 304) of 18 nursing homes. Agitation symptoms were
      clustered using factorial analysis. Depression was estimated using the Dementia
      Mood Assessment Scale (DMAS). Dementia severity was assessed categorically using
      predefined cut-off scores derived from the Mini-Mental State Examination (MMSE).
      The relationship between agitation and its sub-syndromes, depression, and
      dementia severity was calculated using chi 2-statistics. Linear regression
      analyses were used to calculate the effect of dementia severity and psychotropic
      prescriptions on agitation and depression, controlling for age and gender.
      RESULTS: Increasing stages of dementia severity were associated with higher risk
      for physically aggressive (p < 0.001) and non-aggressive (p < 0.01) behaviors,
      verbally agitated behavior (p < 0.05), and depression (p < 0.001). Depressive
      symptoms were associated with physically aggressive (p < 0.001) and verbally
      agitated (p < 0.05) behaviors, beyond the effects of dementia severity.
      Prescription of antipsychotics was correlated with depression and all agitation
      sub-syndromes except hiding and hoarding. CONCLUSIONS: Dementia severity is a
      predictor for agitation and depression. Beyond that, depression increased with
      dementia severity, and the severity of depression was associated with both
      physically and verbally aggressive behaviors, indicating that, in advanced stages
      of dementia, depression in some patients might underlie aggressive behavior.

PMID- 22591586
TI  - One-pot primary aminomethylation of aryl and heteroaryl halides with sodium
      phthalimidomethyltrifluoroborate.
AB  - A one-pot primary aminomethylation of aryl halides, triflates, mesylates, and
      tosylates via Suzuki-Miyaura cross-coupling reactions with sodium
      phthalimidomethyltrifluoroborate followed by deamidation with ethylenediamine is
      reported.

PMID- 22591588
TI  - Safety evaluation of a recombinant plasmin derivative lacking kringles 2-5 and rt
      PA in a rat model of transient ischemic stroke.
AB  - BACKGROUND: Tissue type plasminogen activator is the only approved thrombolytic
      agent for the treatment of ischemic stroke. However, it carries the disadvantage
      of a 10-fold increase in symptomatic and asymptomatic intracranial hemorrhage. A
      safer thrombolytic agent may improve patient prognosis and increase patient
      participation in thrombolytic treatment. A novel direct-acting thrombolytic
      agent, Delta(K2-K5) plasmin, promising an improved safety profile was examined
      for safety in the snare ligature model of stroke in the rat. METHODS: Male
      spontaneously hypertensive rats were subjected to 6 hours middle cerebral artery
      occlusion followed by 18 hours reflow. Beginning 1 minute before reflow, they
      were dosed with saline, vehicle, Delta(K2-K5) plasmin (0.15, 0.5, 1.5, and 5
      mg/kg) or recombinant tissue-type plasminogen activator (10 and 30 mg/kg) by
      local intra-arterial infusion lasting 10 to 60 minutes. The rats were assessed
      for bleeding score, infarct volume, modified Bederson score and general
      behavioral score. In a parallel study, temporal progression of infarct volume was
      determined. In an in vitro study, whole blood clots from humans, canines and rats
      were exposed to Delta(K2-K5). Clot lysis was monitored by absorbance at 280 nm.
      RESULTS: The main focus of this study was intracranial hemorrhage safety.
      Delta(K2-K5) plasmin treatment at the highest dose caused no more intracranial
      hemorrhage than the lowest dose of recombinant tissue type plasminogen activator,
      but showed at least a 5-fold superior safety margin. Secondary results include:
      temporal infarct volume progression shows that the greatest expansion of infarct
      volume occurs within 2-3 hours of middle cerebral artery occlusion in the
      spontaneously hypertensive rat. A spike in infarct volume was observed at 6 hours
      ischemia with reflow. Delta(K2-K5) plasmin tended to reduce infarct volume and
      improve behavior compared to controls. In vitro data suggests that Delta(K2-K5)
      plasmin is equally effective at lysing clots from humans, canines and rats.
      CONCLUSIONS: The superior intracranial hemorrhage safety profile of the direct
      acting thrombolytic Delta(K2-K5) plasmin compared with recombinant tissue type
      plasminogen activator makes this agent a good candidate for clinical evaluation
      in the treatment of acute ischemic stroke.

PMID- 22591590
TI  - Impact of physician assistance on the reliability of the International Index of
      Erectile Function.
AB  - The aim of this study was to analyse the impact of assistance on the
      comprehensibility and reliability of the Turkish version of International Index
      of Erectile Function (IIEF). In this study, 458 patients were asked to complete
      the IIEF questionnaire by themselves during their first visit and then once again
      during their second visit with the assistance of a physician. The impact of
      physician assistance was evaluated by comparing the first and second
      questionnaires. The data were analysed using statistical package software (spss).
      A t test, Cronbach's alpha analysis, test-retest correlation (Pearson) and
      comparison of two rates between two independent groups test were used to analyse
      the impact of physician assistance. A P value <0.05 was considered to be
      significant. The proportions of the patients who completed the questionnaires
      were 70.9% and 100% at the first and second visit respectively. Physician
      assistance significantly increased the number of patients who completed the
      questionnaire among patients >= 60 years old (P = 0.0009) and in patients with
      low levels of education (P = 0.0001). The Cronbach's alpha coefficients were
      0.782 and 0.917 for the first and second questionnaires respectively. A high
      degree of internal consistency was observed for the 'physician-assisted'
      questionnaire (P < 0.001), and relatively less internal consistency was found for
      the 'self-administered' questionnaire (P < 0.05) A relatively weaker correlation
      was found between the first and second questionnaires in primary school graduates
      (r = 0.391, P < 0.05) and in patients >= 60 years old (r = 0.433, P < 0.05).
      There was a significant difference between the 'self-administered' and 'physician
      assisted' IIEF scores in patients >= 60 years old (P < 0.0001) and primary school
      graduates (P < 0.0001). Physician assistance increased the comprehensibility and
      reliability of the IIEF questionnaire, especially in elderly patients and in
      patients with low education levels.

PMID- 22591589
TI  - Scapula alata in early breast cancer patients enrolled in a randomized clinical
      trial of post-surgery short-course image-guided radiotherapy.
AB  - BACKGROUND: Scapula alata (SA) is a known complication of breast surgery
      associated with palsy of the serratus anterior, but it is seldom mentioned. We
      evaluated the risk factors associated with SA and the relationship of SA with
      ipsilateral shoulder/arm morbidity in a series of patients enrolled in a trial of
      post-surgery radiotherapy (RT). METHODS: The trial randomized women with
      completely resected stage I-II breast cancer to short-course image-guided RT,
      versus conventional RT. SA, arm volume and shoulder-arm mobility were measured
      prior to RT and at one to three months post-RT. Shoulder/arm morbidities were
      computed as a post-RT percentage change relative to pre-RT measurements. RESULTS:
      Of 119 evaluable patients, 13 (= 10.9%) had pre-RT SA. Age younger than 50 years
      old, a body mass index less than 25 kg/m2, and axillary lymph node dissection
      were significant risk factors, with odds ratios of 4.8 (P = 0.009), 6.1 (P =
      0.016), and 6.1 (P = 0.005), respectively. Randomization group was not
      significant. At one to three months' post-RT, mean arm volume increased by 4.1%
      (P = 0.036) and abduction decreased by 8.6% (P = 0.046) among SA patients, but
      not among non-SA patients. SA resolved in eight, persisted in five, and appeared
      in one patient. CONCLUSION: The relationship of SA with lower body mass index
      suggests that SA might have been underestimated in overweight patients. Despite
      apparent resolution of SA in most patients, pre-RT SA portended an increased risk
      of shoulder/arm morbidity. We argue that SA warrants further investigation.
      Incidentally, the observation of SA occurring after RT in one patient represents
      the second case of post-RT SA reported in the literature.

PMID- 22591592
TI  - An ethnobotanical survey of medicinal plants used in Terai forest of western
      Nepal.
AB  - BACKGROUND: Nepal Himalayas have been known as a rich source for valuable
      medicinal plants since Vedic periods. Present work is the documentation of
      indigenous knowledge on plant utilization as natural remedy by the inhabitants of
      terai forest in Western Nepal. METHODS: Study was conducted during 2010-2011
      following standard ethnobotanical methods. Data about medicinal uses of plants
      were collected by questionnaire, personal interview and group discussion with pre
      identified informants. Voucher specimens were collected with the help of
      informants, processed into herbarium following standard methods, identified with
      the help of pertinent floras and taxonomic experts, and submitted in Department
      of Botany, Butwal Multiple Campus, Tribhuvan University, Nepal for future
      references. RESULTS: During the present study 66 medicinal plant species
      belonging to 37 families and 60 genera has been documented. These plants were
      used to treat various diseases and ailments grouped under 11 disease categories,
      with the highest number of species (41) being used for gastro-intestinal
      disorders, followed by dermatological disorders (34). In the study area the
      informants' consensus about usages of medicinal plants ranges from 0.93 to 0.97
      with an average value of 0.94. Herbs (53%) were the primary source of medicine,
      followed by trees (23%). Curcuma longa (84%) and Azadirachta indica (76%) are the
      most frequently and popularly used medicinal plant species in the study area.
      Acacia catechu, Bacopa monnieri, Bombax ceiba, Drymaria diandra, Rauvolfia
      serpentina, and Tribulus terrestris are threatened species which needs to be
      conserved for future use. CONCLUSIONS: The high degree of consensus among the
      informants suggests that current use and knowledge are still strong, and thus the
      preservation of today's knowledge shows good foresight in acting before much has
      been lost. The connections between plant use and conservation are also important
      ones, especially as the authors note that neither the local inhabitants nor the
      government is addressing the potential loss of valuable species in this region.

PMID- 22591593
TI  - Designing a physical activity parenting course: parental views on recruitment,
      content and delivery.
AB  - BACKGROUND: Many children do not engage in sufficient levels of physical activity
      (PA) and spend too much time screen-viewing (SV). High levels of SV (e.g.
      watching TV, playing video games and surfing the internet) and low levels of PA
      have been associated with adverse health outcomes. Parenting courses may hold
      promise as an intervention medium to change children's PA and SV. The current
      study was formative work conducted to design a new parenting programme to
      increase children's PA and reduce their SV. Specifically, we focussed on interest
      in a course, desired content and delivery style, barriers and facilitators to
      participation and opinions on control group provision. METHODS: In-depth
      telephone interviews were conducted with thirty two parents (29 female) of 6-8
      year olds. Data were analysed thematically. An anonymous online survey was also
      completed by 750 parents of 6-8 year old children and descriptive statistics
      calculated. RESULTS: Interview participants were interested in a parenting course
      because they wanted general parenting advice and ideas to help their children be
      physically active. Parents indicated that they would benefit from knowing how to
      quantify their child's PA and SV levels. Parents wanted practical ideas of
      alternatives to SV. Most parents would be unable to attend unless childcare was
      provided. Schools were perceived to be a trusted source of information about
      parenting courses and the optimal recruitment location. In terms of delivery
      style, the majority of parents stated they would prefer a group-based approach
      that provided opportunities for peer learning and support with professional
      input. Survey participants reported the timing of classes and the provision of
      childcare were essential factors that would affect participation. In terms of
      designing an intervention, the most preferred control group option was the
      opportunity to attend the same course at a later date. CONCLUSIONS: Parents are
      interested in PA/SV parenting courses but the provision of child care is
      essential for attendance. Recruitment is likely to be facilitated via trusted
      sources. Parents want practical advice on how to overcome barriers and suggest
      advice is provided in a mutually supportive group experience with expert input.

PMID- 22591594
TI  - Illness burden and symptoms of anxiety in older adults: optimism and pessimism as
      moderators.
AB  - BACKGROUND: We assessed the association between medical illness burden and
      anxiety symptoms, hypothesizing that greater illness burden would be associated
      with symptoms of anxiety, and that optimism would buffer, while pessimism would
      exacerbate, this relationship. METHODS: We recruited 109 older adults, aged 65
      years and older, from primary care and geriatric clinics to participate in this
      cross-sectional, interview-based study. Participants completed the Snaith
      Clinical Anxiety Scale and the Life Orientation Test - Revised, a measure of
      optimism/pessimism. A physician-rated measure of illness burden, the Cumulative
      Illness Rating Scale, was also administered. RESULTS: Supporting our hypotheses,
      greater levels of overall optimism weakened, and pessimism strengthened, the
      association between illness burden and anxiety symptoms, after accounting for the
      effects of demographic, cognitive, functional, and psychological covariates.
      CONCLUSIONS: Bolstering positive and reducing negative future expectancies may
      aid in the prevention of psychological distress in medically ill older adults.
      Therapeutic strategies to enhance optimism and reduce pessimism, which may be
      well-suited to primary care and other medical settings, and to which older adults
      may be particularly amenable, may contribute to reduced health-related anxiety.

PMID- 22591595
TI  - Mapping populations at risk: improving spatial demographic data for infectious
      disease modeling and metric derivation.
AB  - The use of Global Positioning Systems (GPS) and Geographical Information Systems
      (GIS) in disease surveys and reporting is becoming increasingly routine, enabling
      a better understanding of spatial epidemiology and the improvement of
      surveillance and control strategies. In turn, the greater availability of
      spatially referenced epidemiological data is driving the rapid expansion of
      disease mapping and spatial modeling methods, which are becoming increasingly
      detailed and sophisticated, with rigorous handling of uncertainties. This
      expansion has, however, not been matched by advancements in the development of
      spatial datasets of human population distribution that accompany disease maps or
      spatial models.Where risks are heterogeneous across population groups or space or
      dependent on transmission between individuals, spatial data on human population
      distributions and demographic structures are required to estimate infectious
      disease risks, burdens, and dynamics. The disease impact in terms of morbidity,
      mortality, and speed of spread varies substantially with demographic profiles, so
      that identifying the most exposed or affected populations becomes a key aspect of
      planning and targeting interventions. Subnational breakdowns of population counts
      by age and sex are routinely collected during national censuses and maintained in
      finer detail within microcensus data. Moreover, demographic and health surveys
      continue to collect representative and contemporary samples from clusters of
      communities in low-income countries where census data may be less detailed and
      not collected regularly. Together, these freely available datasets form a rich
      resource for quantifying and understanding the spatial variations in the sizes
      and distributions of those most at risk of disease in low income regions, yet at
      present, they remain unconnected data scattered across national statistical
      offices and websites.In this paper we discuss the deficiencies of existing
      spatial population datasets and their limitations on epidemiological analyses. We
      review sources of detailed, contemporary, freely available and relevant spatial
      demographic data focusing on low income regions where such data are often sparse
      and highlight the value of incorporating these through a set of examples of their
      application in disease studies. Moreover, the importance of acknowledging,
      measuring, and accounting for uncertainty in spatial demographic datasets is
      outlined. Finally, a strategy for building an open-access database of spatial
      demographic data that is tailored to epidemiological applications is put forward.

PMID- 22591596
TI  - Marine crude-oil biodegradation: a central role for interspecies interactions.
AB  - The marine environment is highly susceptible to pollution by petroleum, and so
      it is important to understand how microorganisms degrade hydrocarbons, and
      thereby mitigate ecosystem damage. Our understanding about the ecology,
      physiology, biochemistry and genetics of oil-degrading bacteria and fungi has
      increased greatly in recent decades; however, individual populations of microbes
      do not function alone in nature. The diverse array of hydrocarbons present in
      crude oil requires resource partitioning by microbial populations, and microbial
      modification of oil components and the surrounding environment will lead to
      temporal succession. But even when just one type of hydrocarbon is present, a
      network of direct and indirect interactions within and between species is
      observed. In this review we consider competition for resources, but focus on some
      of the key cooperative interactions: consumption of metabolites, biosurfactant
      production, provision of oxygen and fixed nitrogen. The emphasis is largely on
      aerobic processes, and especially interactions between bacteria, fungi and
      microalgae. The self-construction of a functioning community is central to
      microbial success, and learning how such "microbial modules" interact will be
      pivotal to enhancing biotechnological processes, including the bioremediation of
      hydrocarbons.

PMID- 22591597
TI  - Evaluation of a genetically modified foot-and-mouth disease virus vaccine
      candidate generated by reverse genetics.
AB  - BACKGROUND: Foot-and-mouth disease (FMD) is the most economically important and
      highly contagious disease of cloven-hoofed animals worldwide. Control of the
      disease has been mainly based on large-scale vaccinations with whole-virus
      inactivated vaccines. In recent years, a series of outbreaks of type O FMD
      occurred in China (including Chinese Taipei, Chinese Hong Kong) posed a
      tremendous threat to Chinese animal husbandry. Its causative agent, type O FMDV,
      has evolved into three topotypes (East-South Asia (ME-SA), Southeast Asia (SEA),
      Cathay (CHY)) in these regions, which represents an important obstacle to disease
      control. The available FMD vaccine in China shows generally good protection
      against ME-SA and SEA topotype viruses infection, but affords insufficient
      protection against some variants of the CHY topotype. Therefore, the choice of a
      new vaccine strain is of fundamental importance. RESULTS: The present study
      describes the generation of a full-length infectious cDNA clone of FMDV vaccine
      strain and a genetically modified virus with some amino acid substitutions in
      antigenic sites 1, 3, and 4, based on the established infectious clone. The
      recombinant viruses had similar growth properties to the wild O/HN/CHA/93 virus.
      All swine immunized with inactivated vaccine prepared from the O/HN/CHA/93 were
      fully protected from challenge with the viruses of ME-SA and SEA topotypes and
      partially protected against challenge with the virus of CHY topotype at 28 days
      post-immunization. In contrast, the swine inoculated with the genetically
      modified vaccine were completely protected from the infection of viruses of the
      three topotypes. CONCLUSIONS: Some amino acid substitutions in the FMDV vaccine
      strain genome did not have an effect on the ability of viral replication in
      vitro. The vaccine prepared from genetically modified FMDV by reverse genetics
      significantly improved the protective efficacy to the variant of the CHY
      topotype, compared with the wild O/HN/CHA/93 virus. Thus, the full-length cDNA
      clone of FMDV can be a useful tool to develop genetically engineered FMDV vaccine
      candidates to help control porcinophilic FMD epidemics in China.

PMID- 22591600
TI  - A successful model of Road Traffic Injury surveillance in a developing country:
      process and lessons learnt.
AB  - BACKGROUND: Road Traffic Injuries (RTIs) are one of the leading causes of death
      and disability worldwide with 90% of global mortality concentrated in the low and
      middle income countries. RTI surveillance is recommended to define the burden,
      identify high risk groups, plan intervention and monitor their impact. Despite
      its stated importance in the literature, very few examples of sustained
      surveillance systems are reported from low income countries. This paper shares
      the experience of setting up an urban RTI surveillance program in the emergency
      departments of five major hospitals in Karachi, Pakistan. METHOD: We describe the
      process of establishing a surveillance system including assembling a multi
      institution research group, developing a data collection methodology, carrying
      out data collection and analysis and dissemination of information to the relevant
      stakeholders. In the absence of a road safety agency, the surveillance system
      required developing individual partnerships with industry, police, city
      government, media and many other stakeholders. Impact of the surveillance is
      demonstrated by some initiatives in the local trauma system and improvements in
      road design to effect hazard reduction. CONCLUSION: We demonstrated that a
      functional RTI surveillance program can be established, and effectively managed
      in a developing country, despite lack of infrastructure and limitation of
      resources. Data utilization in the absence of well defined road safety
      infrastructure within the government is a challenge. More effective actions are
      hampered by the limited capacity in the transport and health sectors to do in
      depth analysis through road safety audits and trauma registries.

PMID- 22591601
TI  - Antipsychotic use and diagnosis of delirium in the intensive care unit.
AB  - INTRODUCTION: Delirium is an independent risk factor for prolonged hospital
      length of stay (LOS) and increased mortality. Several antipsychotics have been
      studied for the treatment of intensive care unit (ICU) delirium that has led to a
      high variability in prescribing patterns for these medications. We hypothesize
      that in clinical practice the documentation of delirium is lower than the
      incidence of delirium reported in prospective clinical trials. The objective of
      this study was to document the incidence of delirium diagnosed in ICU patients
      and to describe the utilization of antipsychotics in the ICU. METHODS: This was a
      retrospective, observational, cohort study conducted at 71 United States academic
      medical centers that reported data to the University Health System Consortium
      Clinical Database/Resource Manager. It included all patients 18 years of age and
      older admitted to the hospital between 1 January 2010 and 30 June 2010 with at
      least one day in the ICU. RESULTS: Delirium was diagnosed in 6% (10,034 of
      164,996) of hospitalizations with an ICU admission. Antipsychotics were
      administered to 11% (17,764 of 164,996) of patients. Of the antipsychotics
      studied, the most frequently used were haloperidol (62%; n = 10,958) and
      quetiapine (31%; n = 5,448). Delirium was associated with increased ICU LOS (5
      vs. 3 days, P < 0.001) and hospital LOS (11 vs. 6 days, P < 0.001), but not in
      hospital mortality (8% vs. 9%, P = 0.419). Antipsychotic exposure was associated
      with increased ICU LOS (8 vs. 3 days, P < 0.001), hospital LOS (14 vs. 5 days, P
      < 0.001) and mortality (12% vs. 8%, P < 0.001). Of patients with antipsychotic
      exposure in the ICU, absence of a documented mental disorder (32%, n = 5,760) was
      associated with increased ICU LOS (9 vs. 7 days, P < 0.001), hospital LOS (16 vs.
      13 days, P < 0.001) and in-hospital mortality (19% vs. 9%, P < 0.001) compared to
      patients with a documented mental disorder (68%, n = 12,004). CONCLUSIONS: The
      incidence of documented delirium in ICU patients is lower than that documented in
      previous prospective studies with active screening. Antipsychotics are
      administered to 1 in every 10 ICU patients. When administration occurs in the
      absence of a documented mental disorder, antipsychotic use is associated with an
      even higher ICU and hospital LOS, as well as in-hospital mortality.

PMID- 22591598
TI  - Personalized medicine: is it a pharmacogenetic mirage?
AB  - The notion of personalized medicine has developed from the application of the
      discipline of pharmacogenetics to clinical medicine. Although the clinical
      relevance of genetically-determined inter-individual differences in
      pharmacokinetics is poorly understood, and the genotype-phenotype association
      data on clinical outcomes often inconsistent, officially approved drug labels
      frequently include pharmacogenetic information concerning the safety and/or
      efficacy of a number of drugs and refer to the availability of the
      pharmacogenetic test concerned. Regulatory authorities differ in their approach
      to these issues. Evidence emerging subsequently has generally revealed the
      pharmacogenetic information included in the label to be premature. Revised drugs
      labels, together with a flurry of other collateral activities, have raised public
      expectations of personalized medicine, promoted as 'the right drug at the right
      dose the first time.' These expectations place the prescribing physician in a
      dilemma and at risk of litigation, especially when evidence-based information on
      genotype-related dosing schedules is to all intent and purposes non-existent and
      guidelines, intended to improve the clinical utility of available pharmacogenetic
      information or tests, distance themselves from any responsibility. Lack of
      efficacy or an adverse drug reaction is frequently related to non-genetic
      factors. Phenoconversion, arising from drug interactions, poses another often
      neglected challenge to any potential success of personalized medicine by
      mimicking genetically-determined enzyme deficiency. A more realistic promotion of
      personalized medicine should acknowledge current limitations and emphasize that
      pharmacogenetic testing can only improve the likelihood of diminishing a specific
      toxic effect or increasing the likelihood of a beneficial effect and that
      application of pharmacogenetics to clinical medicine cannot adequately predict
      drug response in individual patients.

PMID- 22591603
TI  - Photochemistry of o-fluoranil.
AB  - Initial exploration of the photochemical behavior of o-fluoranil has revealed
      dimer formation, cycloaddition to alkenes, and hydrogen abstraction from
      hydrocarbons, aldehydes, and ethers.

PMID- 22591602
TI  - Prevalence of and factors associated with daily smoking among Inner Mongolia
      medical students in China: a cross-sectional questionnaire survey.
AB  - BACKGROUND: To date, no study on smoking behavior of medical students in Inner
      Mongolia has been reported. The aim of the present study was to determine the 1
      month prevalence of and factors associated with daily smoking among medical
      students in Inner Mongolia of China, to assist interventions designed to reduce
      the smoking behavior of medical college students in this region. METHODS: During
      December 2010 and January 2011 a cross-sectional survey was conducted among
      medical students at the Inner Mongolia Medical College using a self-administered
      questionnaire. The questionnaire consisted of three sections: students' basic
      information, attitude on smoking behavior, and smoking status of the student
      daily smokers. Students who smoked every day in the last 30 days were regarded as
      daily smokers. Factors associated with smoking were identified using binary
      logistic regression analysis. RESULTS: A total of 6044 valid surveys were
      returned. The overall prevalence of daily smoking was 9.8% while the prevalence
      of daily smoking among males and females were 29.4% and 1.7%, respectively. Males
      in the Faculty of Medicine Information Management had the highest daily smoking
      rate (48.9%). Logistic regression models found that the main factors associated
      with daily smoking among male medical students were highest year of study (OR =
      3.62; CI: 1.18-11.05); attitude towards smoking behavior Do not care about people
      smoking around you (OR = 2.75; CI: 2.08-3.64); and Smoking is harmful to their
      health (OR = 4.40; CI: 2.21-8.75). The main factor associated with daily smoking
      among female medical students was attitude towards smoking behavior Eliminate
      smoking on campus (OR = 0.11; CI: 0.06-0.23). Both for male and female medical
      students, there was no association between ethnicity and cigarette daily smoking.
      In regard to smoking status, more than 60% of daily smokers began smoking in high
      school, 61.3% smoked less than 5 cigarettes per day, 62.9% of the daily smokers'
      families opposed their smoking behavior, and after an hour of not smoking 74.6%
      daily smokers did not feel uncomfortable. CONCLUSIONS: Antismoking education
      should be further promoted in Inner Mongolia medical students, with consideration
      given to the factors associated with daily smoking behavior found in the present
      study.

PMID- 22591605
TI  - Are HIV-infected patients a high-risk population for hepatitis E virus infection
      in Spain?

PMID- 22591606
TI  - Novel high-sensitive D-dimer determination predicts chemotherapy-associated
      venous thromboembolism in intermediate risk lung cancer patients.
AB  - INTRODUCTION: We hypothesized that the use of a novel high sensitivity (HS) assay
      for D-dimer determination might ameliorate venous thromboembolism (VTE) risk
      prediction in intermediate risk lung cancer patients in whom chemotherapy could
      act as a trigger for VTE onset. PATIENTS AND METHODS: Pretreatment HS D-dimer
      levels were retrospectively evaluated in 108 lung cancer outpatients using a
      novel automated latex enhanced turbidimetric immunoassay. All patients were at
      the start of a new platinum-based chemotherapy regimen and were classified as
      intermediate risk according to Khorana's assessment model. Patients were followed
      up for a median period of 6.9 months. RESULTS: Receiver operating characteristic
      (ROC) curves and corresponding Bayesian analysis showed that the best performance
      was obtained at a cutoff level of 1500 ng/mL, which resulted in a sensitivity of
      81%, a specificity of 69%, a positive predictive value (PPV) of 31%, a negative
      predictive value (NPV) of 96%, and an accuracy of 70%. Patients with HS D-dimer
      levels above the cutoff had a worse VTE-free survival (60%) compared with those
      with levels below the cutoff (95%; P = .0001). Multivariate Cox proportional
      hazards survival analysis confirmed that pretreatment HS D-dimer levels were able
      to significantly predict VTE with a hazard ratio of 11 (95% confidence interval,
      2.62-46.2; P = .001), independently of classic VTE risk factors. CONCLUSIONS: The
      use of HS D-dimer determination prior to chemotherapy might allow for VTE risk
      stratification of intermediate risk cancer patients, helping in identifying those
      individuals who could benefit from thromboprophylaxis.

PMID- 22591604
TI  - Oocyte activation and phospholipase C zeta (PLCzeta): diagnostic and therapeutic
      implications for assisted reproductive technology.
AB  - Infertility affects one in seven couples globally and has recently been
      classified as a disease by the World Health Organisation (WHO). While in-vitro
      fertilisation (IVF) offers effective treatment for many infertile couples, cases
      exhibiting severe male infertility (19-57%) often remain difficult, if not
      impossible to treat. In such cases, intracytoplasmic sperm injection (ICSI), a
      technique in which a single sperm is microinjected into the oocyte, is
      implemented. However, 1-5% of ICSI cycles still fail to fertilise, affecting over
      1000 couples per year in the UK alone. Pregnancy and delivery rates for IVF and
      ICSI rarely exceed 30% and 23% respectively. It is therefore imperative that
      Assisted Reproductive Technology (ART) protocols are constantly modified by
      associated research programmes, in order to provide patients with the best
      chances of conception. Prior to fertilisation, mature oocytes are arrested in the
      metaphase stage of the second meiotic division (MII), which must be alleviated to
      allow the cell cycle, and subsequent embryogenesis, to proceed. Alleviation
      occurs through a series of concurrent events, collectively termed 'oocyte
      activation'. In mammals, oocytes are activated by a series of intracellular
      calcium (Ca2+) oscillations following gamete fusion. Recent evidence implicates a
      sperm-specific phospholipase C, PLCzeta (PLCzeta), introduced into the oocyte
      following membrane fusion as the factor responsible. This review summarises our
      current understanding of oocyte activation failure in human males, and describes
      recent advances in our knowledge linking certain cases of male infertility with
      defects in PLCzeta expression and activity. Systematic literature searches were
      performed using PubMed and the ISI-Web of Knowledge. Databases compiled by the
      United Nations and World Health Organisation databases (UNWHO), and the Human
      Fertilization and Embryology Authority (HFEA) were also scrutinised. It is clear
      that PLCzeta plays a fundamental role in the activation of mammalian oocytes, and
      that genetic, molecular, or biochemical perturbation of this key enzyme is
      strongly linked to human infertility where oocyte activation is deficient.
      Consequently, there is significant scope for our understanding of PLCzeta to be
      translated to the ART clinic, both as a novel therapeutic agent with which to
      rescue oocyte activation deficiency (OAD), or as a prognostic/diagnostic
      biomarker of oocyte activation ability in target sperm samples.

PMID- 22591607
TI  - Identifying barriers associated with enrollment of patients with lung cancer into
      clinical trials.
AB  - BACKGROUND: Enrollment of patients with lung cancer into clinical trials is
      required to accelerate the pace of new therapy development and contribute to a
      better understanding of the biological characteristics of cancer. METHODS: We
      conducted a retrospective chart review of all patients seen by the thoracic
      medical oncology team at the Vanderbilt Ingram Cancer Center (VICC) from November
      2005 to November 2008 to determine the barriers associated with patient
      enrollment in to clinical trials. RESULTS: One thousand forty-three patient
      charts were audited: 32% of patients were eligible for enrollment, and 14%
      enrolled in a study. There were no significant differences in protocol
      availability or eligibility by sex, smoking status, or age. Patients living
      further from the cancer center were significantly less likely to have a study
      protocol available (P = .009), but if a protocol was available they were more
      likely to be eligible for enrollment (P < .001). Significantly more protocols
      were available for patients with non-small-cell lung cancer (NSCLC) compared with
      those who had small-cell lung cancer (SCLC) (63% vs. 48%; P < .001). Patients
      with advanced disease were more likely to have a protocol available (P < .001)
      and enter a study (P = .031). The most common reasons for patients not being
      eligible for enrollment were poor performance status (32%) and presence of
      comorbid disease (27%). The most common reasons for potentially eligible patients
      not enrolling in a study included preference for treatment closer to home (49%)
      and patient refusal (43%). CONCLUSION: Additional strategies are required to
      increase accrual of patients into lung cancer trials, including development of
      protocols for early-stage disease and modifying eligibility and performance
      status criteria for this unique patient population.

PMID- 22591608
TI  - Material-driven differentiation of induced pluripotent stem cells in neuron
      growth factor-grafted poly(epsilon-caprolactone)-poly(beta-hydroxybutyrate)
      scaffolds.
AB  - The potential of constructs comprising induced pluripotent stem (iPS) cells and
      biopolymers can be high for neurological surgery practice, if the systematic
      activity of neuronal regeneration is clarified. This study shows a guided
      differentiation of iPS cells toward neurons in neuron growth factor (NGF)-grafted
      poly(epsilon-caprolactone) (PCL)-poly(beta-hydroxybutyrate) (PHB) scaffolds. The
      porosity of PCL-PHB scaffolds enhanced with increasing the concentration of salt
      particles (porogen) and the weight percentage of PCL. An increase in the graft
      concentration of NGF elevated the atomic ratios of N/C and O/C on the surface of
      NGF-grafted PCL-PHB scaffolds. In addition, incorporating heparin and NGF
      promoted the adhesion and viability of iPS cells in constructs. When the weight
      percentage of PCL increased, the viability of iPS cells reduced; however, more
      PCL in constructs benefited the adhesion of iPS cells. Under the influence of
      heparin and NGF, a high weight percentage of PCL and a long inductive period
      improved iPS cells to differentiate into neuron-like cells carrying betaIII
      tubulin and inhibited other differentiation(s). The material-driven
      differentiation in NGF-grafted PCL-PHB constructs can be promising in guiding iPS
      cells to produce neurons for nerve tissue engineering.

PMID- 22591609
TI  - Intracranial MEMS based temozolomide delivery in a 9L rat gliosarcoma model.
AB  - Primary malignant brain tumors (BT) are the most common and aggressive malignant
      brain tumor. Treatment of BTs is a daunting task with median survival just at 21
      months. Methods of localized delivery have achieved success in treating BT by
      circumventing the blood brain barrier and achieving high concentrations of
      therapeutic within the tumor. The capabilities of localized delivery can be
      enhanced by utilizing mirco-electro-mechanical systems (MEMS) technology to
      deliver drugs with precise temporal control over release kinetics. An
      intracranial MEMS based device was developed to deliver the clinically utilized
      chemotherapeutic temozolomide (TMZ) in a rodent glioma model. The device is a
      liquid crystalline polymer reservoir, capped by a MEMS microchip. The microchip
      contains three nitride membranes that can be independently ruptured at any point
      during or after implantation. The kinetics of TMZ release were validated and
      quantified in vitro. The safety of implanting the device intracranially was
      confirmed with preliminary in vivo studies. The impact of TMZ release kinetics
      was investigated by conducting in vivo studies that compared the effects of drug
      release rates and timing on animal survival. TMZ delivered from the device was
      effective at prolonging animal survival in a 9L rodent glioma model.
      Immunohistological analysis confirmed that TMZ was released in a viable,
      cytotoxic form. The results from the in vivo efficacy studies indicate that
      early, rapid delivery of TMZ from the device results in the most prolonged animal
      survival. The ability to actively control the rate and timing of drug(s) release
      holds tremendous potential for the treatment of BTs and related diseases.

PMID- 22591611
TI  - Direct cell encapsulation in biodegradable and functionalizable carboxybetaine
      hydrogels.
AB  - Hydrogels provide three-dimensional (3D) frames with tissue-like elasticity and
      high water content for tissue scaffolds. They were commonly prepared from
      macromers such as poly(ethylene glycol) diacrylate (PEGDA) via free radical
      polymerization and used to encapsulate cells. Here, we report the direct
      encapsulation of cells into hydrogels using a low-toxic and water-soluble
      monomer, carboxybetaine methacrylate (CBMA), via redox polymerization. A
      disulfide-containing crosslinker was added to form a biodegradable carboxybetaine
      (CB) hydrogel, which can be self-degraded as cells grow or degraded in an
      accelerating way via adding of a cysteine-contained medium NIH-3T3 cells
      encapsulated in the CB hydrogel formed spherical aggregates that were recovered
      from hydrogel erosion. Furthermore, an RGD-containing peptide was also added to
      improve cell adhesion on the two-dimensional (2D) hydrogel surface and promote
      cell proliferation in the 3D hydrogel. The non-cytotoxic and biodegradable CB
      hydrogel with additional cell-adhesion moieties provides an excellent 3D
      environment for cell growth as tissue scaffolds.

PMID- 22591610
TI  - Tubular hydrogels of circumferentially aligned nanofibers to encapsulate and
      orient vascular cells.
AB  - There is a great clinical need for tissue engineered blood vessels that could be
      used to replace or bypass damaged arteries. The success of such grafts will
      depend strongly on their ability to mimic the cellular and matrix organization
      found in native arteries, but currently available cell scaffolds such as
      electrospun fibers or hydrogels lack the ability to simultaneously encapsulate
      and align cells. Our laboratory has recently developed liquid crystalline
      solutions of peptide amphiphile nanofibers that form aligned domains at
      exceedingly low concentrations (<1 wt%), and can be trapped as gels with
      macroscopic alignment using low shear rates and ionic crosslinking. We describe
      here the use of these systems to fabricate tubes with macroscopic circumferential
      alignment and demonstrate their potential as arterial cell scaffolds. The
      nanofibers in these tubes were circumferentially aligned by applying small
      amounts of shear in a custom built flow chamber prior to gelation. Small angle X
      ray scattering confirmed that the direction of nanofiber alignment was the same
      as the direction of shear flow. We also show the encapsulation of smooth muscle
      cells during the fabrication process without compromising cell viability. After
      two days in culture the encapsulated cells oriented their long axis in the
      direction of nanofiber alignment thus mimicking the circumferential alignment
      seen in native arteries. Cell density roughly doubled after 12 days demonstrating
      the scaffold's ability to facilitate necessary graft maturation. Since these
      nanofiber gels are composed of >99% water by weight, the cells have abundant room
      for proliferation and remodeling. In contrast to previously reported arterial
      cell scaffolds, this new material can encapsulate cells and direct cellular
      organization without the requirement of external stimuli or gel compaction.

PMID- 22591612
TI  - The tumor accumulation and therapeutic efficacy of doxorubicin carried in calcium
      phosphate-reinforced polymer nanoparticles.
AB  - A mineral (calcium phosphate, CaP)-reinforced core-shell-corona micelle was
      evaluated as a nanocarrier of doxorubicin (DOX) for cancer therapy. The polymer
      micelles of poly(ethylene glycol)-b-poly(L-aspartic acid)-b-poly(L-phenylalanine)
      (PEG-PAsp-PPhe) in the aqueous phase provided the three distinct functional
      domains: the hydrated PEG outer corona for prolonged circulation, the anionic
      PAsp middle shell for CaP mineralization, and the hydrophobic PPhe inner core for
      DOX loading. CaP mineralization was performed by initial electrostatic
      localization of calcium ions at anionic PAsp shells, and the consequent addition
      of phosphate anions to trigger the growth of CaP. The mineralization did not
      affect the micelle size or the spherical morphology. The CaP-mineralized micelles
      exhibited enhanced serum stability. The DOX release from the DOX-loaded
      mineralized micelles (DOX-CaP-PM) at physiological pH was efficiently inhibited,
      whereas at an endosomal pH (pH 4.5), DOX release was facilitated due to the rapid
      dissolution of the CaP mineral layers in the middle shell domains. The in vivo
      tissue distribution and tumor accumulation of the DOX-CaP-PM that were labeled
      with a near-infrared fluorescent (NIRF) dye, Cy5.5, were monitored in MDA-MB231
      tumor-bearing mice. Non-invasive real-time optical imaging results indicated that
      the DOX-CaP-PM exhibited enhanced tumor specificity due to the prolonged stable
      circulation in the blood and an enhanced permeation and retention (EPR) effect
      compared with the DOX-loaded nonmineralized polymer micelles (DOX-NPM). The DOX
      CaP-PM exhibited enhanced therapeutic efficacy in tumor-bearing mice compared
      with free DOX and DOX-NPM. The CaP mineralization on assembled nanoparticles may
      serve as a useful guide for enhancing the antitumor therapeutic efficacy of
      various polymer micelles and nano-aggregates.

PMID- 22591613
TI  - Disaster metrics: quantification of acute medical disasters in trauma-related
      multiple casualty events through modeling of the Acute Medical Severity Index.
AB  - INTRODUCTION: The interaction between the acute medical consequences of a
      Multiple Casualty Event (MCE) and the total medical capacity of the community
      affected determines if the event amounts to an acute medical disaster.
      HYPOTHESIS/PROBLEM: There is a need for a comprehensive quantitative model in MCE
      that would account for both prehospital and hospital-based acute medical systems,
      leading to the quantification of acute medical disasters. Such a proposed model
      needs to be flexible enough in its application to accommodate a priori estimation
      as part of the decision-making process and a posteriori evaluation for total
      quality management purposes. METHODS: The concept proposed by de Boer et al in
      1989, along with the disaster metrics quantitative models proposed by Bayram et
      al on hospital surge capacity and prehospital medical response, were used as
      theoretical frameworks for a new comprehensive model, taking into account both
      prehospital and hospital systems, in order to quantify acute medical disasters.
      RESULTS: A quantitative model called the Acute Medical Severity Index (AMSI) was
      developed. AMSI is the proportion of the Acute Medical Burden (AMB) resulting
      from the event, compared to the Total Medical Capacity (TMC) of the community
      affected; AMSI = AMB/TMC. In this model, AMB is defined as the sum of critical
      (T1) and moderate (T2) casualties caused by the event, while TMC is a function of
      the Total Hospital Capacity (THC) and the medical rescue factor (R) accounting
      for the hospital-based and prehospital medical systems, respectively.
      Qualitatively, the authors define acute medical disaster as "a state after any
      type of Multiple Casualty Event where the Acute Medical Burden (AMB) exceeds the
      Total Medical Capacity (TMC) of the community affected." Quantitatively, an acute
      medical disaster has an AMSI value of more than one (AMB / TMC > 1). An acute
      medical incident has an AMSI value of less than one, without the need for medical
      surge. An acute medical emergency has an AMSI value of less than one with
      utilization of surge capacity (prehospital or hospital-based). An acute medical
      crisis has an AMSI value between 0.9 and 1, approaching the threshold for an
      actual medical disaster. CONCLUSION: A novel quantitative taxonomy in MCE has
      been proposed by modeling the Acute Medical Severity Index (AMSI). This model
      accounts for both hospital and prehospital systems, and quantifies acute medical
      disasters. Prospective applications of various components of this model are
      encouraged to further verify its applicability and validity.

PMID- 22591614
TI  - Outcomes in facial aesthetics in cleft lip and palate surgery: a systematic
      review.
AB  - BACKGROUND: While there are internationally validated outcome measures for speech
      and facial growth in cleft lip and palate patients, there is no such
      internationally accepted system for assessing outcomes in facial aesthetics.
      METHOD: A systematic critical review of the scientific literature from the last
      30 years using PUBMED, Medline and Google Scholar was conducted in-line with the
      PRISMA statement recommendations. This encompassed the most relevant manuscripts
      on aesthetic outcomes in cleft surgery in the English language. RESULTS: Fifty
      three articles were reviewed. Four main means of determining outcome measures
      were found: direct clinical assessment, clinical photograph evaluation, clinical
      videographic assessment and three-dimensional evaluation. Cropped photographs
      were more representative than full face. Most techniques were based on a 5-point
      scale, evolving from the Asher-McDade system. Multiple panel-based assessments
      compared scores from lay or professional raters, the results of which were not
      statistically significant. Various reports based on cohorts were poorly matched
      for gender, age, clinical condition and ethnicity, making their results difficult
      to reproduce. CONCLUSIONS: The large number of outcome measure rating systems
      identified, suggests a lack of consensus and confidence as to a reliable,
      validated and reproducible scoring system for facial aesthetics in cleft
      patients. Many template and lay panel scoring systems are described, yet never
      fully validated. Advanced 3D imaging technologies may produce validated outcome
      measures in the future, but presently there remains a need to develop a robust
      method of facial aesthetic evaluation based on standardised patient photographs.
      We make recommendations for the development of such a system.

PMID- 22591615
TI  - One stage breast reconstruction following prophylactic mastectomy for ptotic
      breasts: the inferior dermal flap and implant.
AB  - INTRODUCTION: Immediate reconstruction following prophylactic mastectomy for
      larger ptotic breasts is difficult. Tissue expansion in these patients often
      results in poor cosmetic outcomes. Autologous options may not be possible due to
      clinical unsuitability or patient choice. Using the inferior dermal flap with
      implant achieves lower pole fullness and allows a one-stop reconstruction in the
      larger ptotic breast. METHODS: The inferior dermal flap and implant was performed
      on ten patients (20 breasts). Average age was 43 (range 36-53). The average BMI
      was 37 (range 32-43). The distance from nipple to IMF varied from 15 cm to 26 cm.
      The average implant size was 533 (range 390-620). Complications were minimal with
      one patient experiencing delayed wound healing at the T-junction and one patient
      developing inferior pole erythema postoperatively that settled with antibiotics.
      CONCLUSION: The inferior dermal flap and implant provides a one-stop
      reconstructive option. It is reliable, safe and maintains the breast envelope
      while giving excellent size, shape and symmetry in the larger ptotic patient.

PMID- 22591616
TI  - [Subcutaneous venous cord as a sign of inferior vena cava thrombosis].

PMID- 22591617
TI  - [Bilateral laparoscopic adrenalectomy due to a phaeochromocytoma in Von Hippel
      Lindau syndrome: a technique with 4 trocars].

PMID- 22591618
TI  - One Health and EcoHealth in Ontario: a qualitative study exploring how holistic
      and integrative approaches are shaping public health practice in Ontario.
AB  - BACKGROUND: There is a growing recognition that many public health issues are
      complex and can be best understood by examining the relationship between human
      health and the health of the ecosystems in which people live. Two approaches, One
      Health and Ecosystem Approaches to Health (EcoHealth), can help us to better
      understand these intricate and complex connections, and appear to hold great
      promise for tackling many modern public health dilemmas. Although both One Health
      and EcoHealth have garnered recognition from numerous health bodies in Canada and
      abroad, there is still a need to better understand how these approaches are
      shaping the practice of public health in Ontario.The purpose of this study was to
      characterize how public health actors in Ontario are influenced by the holistic
      principles which underlie One Health and EcoHealth, and to identify important
      lessons from their experiences. METHODS: Ten semi-structured interviews were
      conducted with ten participants from the public health sphere in Ontario.
      Participants encompassed diverse perspectives including infectious disease, food
      systems, urban agriculture, and environmental health. Interviews were recorded,
      transcribed and analyzed using qualitative content analysis to identify major
      themes and patterns. RESULTS: Four major themes emerged from the interviews: the
      importance of connecting human health with the environment; the role of
      governance in promoting these ideas; the value of partnerships and collaborations
      in public health practice; and the challenge of operationalizing holistic
      approaches to public health. Overall study participants were found to be heavily
      influenced by concepts couched in EcoHealth and One Health literature, despite a
      lack of familiarity with these fields. CONCLUSIONS: Although One Health and
      EcoHealth are lesser known approaches in the public health sphere, their holistic
      and systems-based principles were found to influence the thoughts, values and
      experiences of public health actors interviewed in this study. This study also
      highlights the critical role of governance and partnerships in facilitating a
      holistic approach to health. Further research on governance and partnership
      models, as well as systems-based organizational working practices, is needed to
      close the gap between One Health and EcoHealth theory and public health practice.

PMID- 22591619
TI  - Serotonin regulates amylase secretion and acinar cell damage during murine
      pancreatitis.
AB  - OBJECTIVE: Serotonin (5-hydroxytryptamine, 5-HT) is a potent bioactive molecule
      involved in a variety of physiological processes. In this study, the authors
      analysed whether 5-HT regulates zymogen secretion in pancreatic acinar cells and
      the development of pancreatic inflammation, a potentially lethal disease whose
      pathophysiology is not completely understood. METHODS: 5-HT regulation of zymogen
      secretion was analysed in pancreatic acini isolated from wild-type or tryptophan
      hydoxylase-1 knock-out (TPH1(-/-)) mice, which lack peripheral 5-HT, and in
      amylase-secreting pancreatic cell lines. Pancreatitis was induced by cerulein
      stimulation and biochemical and immunohistochemical methods were used to evaluate
      disease progression over 2 weeks. RESULTS: Absence and reduced intracellular
      levels of 5-HT inhibited the secretion of zymogen granules both ex vivo and in
      vitro and altered cytoskeleton dynamics. In addition, absence of 5-HT resulted in
      attenuated pro-inflammatory response after induction of pancreatitis. TPH1(-/-)
      mice showed limited zymogen release, reduced expression of the pro-inflammatory
      chemokine MCP-1 and minimal leucocyte infiltration compared with wild-type
      animals. Restoration of 5-HT levels in TPH1(-/-) mice recovered the blunted
      inflammatory processes observed during acute pancreatitis. However, cellular
      damage, inflammatory and fibrotic processes accelerated in TPH1(-/-) mice during
      disease progression. CONCLUSIONS: These results identify a 5-HT-mediated
      regulation of zymogen secretion in pancreatic acinar cells. In addition, they
      demonstrate that 5-HT is required for the onset but not for the progression of
      pancreatic inflammation. These findings provide novel insights into the normal
      physiology of pancreatic acinar cells and into the pathophysiology of
      pancreatitis, with potential therapeutic implications.

PMID- 22591620
TI  - Statins and Clostridum difficile: a clinically relevant interaction?

PMID- 22591621
TI  - Are slum dwellers at heightened risk of HIV infection than other urban residents?
      Evidence from population-based HIV prevalence surveys in Kenya.
AB  - In 2008, the global urban population surpassed the rural population and by 2050
      more than 6 billion will be living in urban centres. A growing body of research
      has reported on poor health outcomes among the urban poor but not much is known
      about HIV prevalence among this group. A survey of nearly 3000 men and women was
      conducted in two Nairobi slums in Kenya between 2006 and 2007, where respondents
      were tested for HIV status. In addition, data from the 2008/2009 Kenya
      Demographic and Health Survey were used to compare HIV prevalence between slum
      residents and those living in other urban and rural areas. The results showed
      strong intra-urban differences. HIV was 12% among slum residents compared with 5%
      and 6% among non-slum urban and rural residents, respectively. Generally, men had
      lower HIV prevalence than women although in the slums the gap was narrower. Among
      women, sexual experience before the age of 15 compared with after 19 years was
      associated with 62% higher odds of being HIV positive. There was ethnic variation
      in patterns of HIV infection although the effect depended on the current place of
      residence.

PMID- 22591622
TI  - A pilot prospective study on closed loop controlled ventilation and oxygenation
      in ventilated children during the weaning phase.
AB  - INTRODUCTION: The present study is a pilot prospective safety evaluation of a new
      closed loop computerised protocol on ventilation and oxygenation in stable,
      spontaneously breathing children weighing more than 7 kg, during the weaning
      phase of mechanical ventilation. METHODS: Mechanically ventilated children ready
      to start the weaning process were ventilated for five periods of 60 minutes in
      the following order: pressure support ventilation, adaptive support ventilation
      (ASV), ASV plus a ventilation controller (ASV-CO2), ASV-CO2 plus an oxygenation
      controller (ASV-CO2-O2) and pressure support ventilation again. Based on breath
      by-breath analysis, the percentage of time with normal ventilation as defined by
      a respiratory rate between 10 and 40 breaths/minute, tidal volume > 5 ml/kg
      predicted body weight and end-tidal CO2 between 25 and 55 mmHg was determined.
      The number of manipulations and changes on the ventilator were also recorded.
      RESULTS: Fifteen children, median aged 45 months, were investigated. No adverse
      event and no premature protocol termination were reported. ASV-CO2 and ASV-CO2-O2
      kept the patients within normal ventilation for, respectively, 94% (91 to 96%)
      and 94% (87 to 96%) of the time. The tidal volume, respiratory rate, peak
      inspiratory airway pressure and minute ventilation were equivalent for all
      modalities, although there were more automatic setting changes in ASV-CO2 and ASV
      CO2-O2. Positive end-expiratory pressure modifications by ASV-CO2-O2 require
      further investigation. CONCLUSION: Over the short study period and in this
      specific population, ASV-CO2 and ASV-CO2-O2 were safe and kept the patient under
      normal ventilation most of the time. Further research is needed, especially for
      positive end-expiratory pressure modifications by ASV-CO2-O2. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT01095406.

PMID- 22591623
TI  - Humeral head arthroplasty and its ability to restore original humeral head
      geometry.
AB  - BACKGROUND: Modern prosthetic components are designed to enable restoration of
      proximal humeral morphology, provided that a precise osteotomy of the humeral
      head at the level of the anatomic neck is performed. To determine whether a
      simulated osteotomy and replacement arthroplasty with an idealized implant were
      able to restore original head geometry. MATERIALS AND METHODS: A handheld
      digitizer and surface laser scanner were used to digitize 24 humeri. Computer
      models were used to simulate an osteotomy, performed at the anterior cartilage
      metaphyseal interface, and reconstruct the head with a spherical prosthetic head.
      The head diameter, radius of curvature, and inclination and retroversion angles
      were calculated for each specimen and compared with the original humeral head.
      RESULTS: The simulated osteotomy resulted in a 4.8 degrees  decrease in
      inclination (P < .01) and 11.3 degrees  increase in retroversion (P < .001). The
      radius of curvature in the coronal plane was not significantly different (P =
      .284). However, in the axial plane, the prosthesis was significantly larger than
      the original head for both head diameter (P < .001) and radius of curvature (P <
      .05). DISCUSSION: The study suggests that the humeral head is not a perfect
      segment of a sphere and an osteotomy along the anterior cartilage-metaphyseal
      interface does not remove only the proximal humeral articular surface. Even with
      a fully adaptable prosthetic implant, replacement arthroplasty is not able to
      restore original head geometry. CONCLUSIONS: Alterations to head geometry with
      the osteotomy described may alter the line of force through the prosthetic joint,
      producing eccentric loading at the glenoid, and contribute to early failure.

PMID- 22591624
TI  - In vivo immunoregulatory properties of the novel mitochondria-targeted
      antioxidant SkQ1.
AB  - Reactive oxygen species (ROS) is a group of highly reactive oxygen-containing
      chemicals. ROS are essential for various biological functions, including cell
      survival and growth, proliferation and differentiation. At the same time ROS
      production is connected to a number of disorders, such as chronic inflammation,
      age-related diseases and cancers. In the immune system, ROS are involved in the
      defence of the host organism, immune response and immune regulation. One of the
      main sites of ROS generation in the cell is mitochondrial electron transport. In
      contrast to a number of traditional antioxidants, the novel mitochondria-targeted
      antioxidant SkQ1 exerts its antioxidant properties even in nanomolar
      concentrations. In this work, we investigated immunomodulatory properties of SkQ1
      and demonstrated that treatment of mice with SkQ1 led to a decrease in percentage
      of CD8(+) T cells but not of CD4(+) T cells. We documented a decrease of a
      relative number of naive T cells with a simultaneous increase in percentage of
      effector memory T cells. Central memory T cells had also a trend to be increased
      after SkQ1 treatment. In fraction of dendritic cells, we found an increase in
      percentage of plasmacytoid dendritic cells. In the case of myeloid cells, SkQ1
      treatment decreased significantly the percentage of granulocytes. No effect of
      SkQ1 was observed on regulatory T cells, natural killer cells, natural killer T
      cells, as well as on freshly isolated CD8(+) T or CD4(+) T cells, indicating the
      indirect influence of SkQ1 on immune cells.

PMID- 22591625
TI  - Efficacy of laparoscopic surgery for recurrent hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Although laparoscopic hepatectomy is increasingly performed for
      hepatocellular carcinoma, few studies have investigated the efficacy of
      laparoscopic surgery, including hepatectomy for the treatment of recurrent
      hepatocellular carcinoma. We report the results of our study on the efficacy of
      laparoscopic surgery. METHODOLOGY: Forty-three of 123 hepatocellular carcinoma
      patients underwent laparoscopic surgery in 2002-2009; 16 were treated for
      recurrent hepatocellular carcinoma. The characteristics and postoperative
      outcomes of these 16 patients were retrospectively investigated. RESULTS: Seven
      patients underwent laparoscopic hepatectomy, 1 underwent laparoscopic
      radiofrequency ablation, 7 underwent resection of an extrahepatic metastatic
      tumor and 1 patient received diagnostic assessment. Twelve of the 15 surgical
      patients had a repeat recurrence after surgery. Survival at 2 years was
      significantly higher in patients with intrahepatic vs. extrahepatic recurrence
      (100% vs. 42.9%). In addition, overall survival (51.2 vs. 23.0 months) was
      significantly longer in patients with intrahepatic recurrence, although disease
      free survival (19.2 vs. 10.6 months) was not so. CONCLUSIONS: Laparoscopic
      surgery for recurrent hepatocellular carcinoma enabled precise tumor
      localization, more accurate diagnosis, and more careful selection of therapy
      based on hepatic functional reserve and recurrence type. Laparoscopic surgery
      appears to be an effective, minimally invasive option for the diagnosis and
      treatment of recurrent hepatocellular carcinoma.

PMID- 22591626
TI  - [Insertion of a vena cava filter for deep venous thrombosis during pregnancy].

PMID- 22591627
TI  - [Laparotomy in a patient with "body-packer" syndrome].

PMID- 22591628
TI  - European Association of Urology guidelines on Male Infertility: the 2012 update.
AB  - CONTEXT: New data regarding the diagnosis and treatment of male infertility have
      emerged and led to an update of the European Association of Urology (EAU)
      guidelines for Male Infertility. OBJECTIVE: To review the new EAU guidelines for
      Male Infertility. EVIDENCE ACQUISITION: A comprehensive work-up of the literature
      obtained from Medline, the Cochrane Central Register of Systematic Reviews, and
      reference lists in publications and review articles was developed and screened by
      a group of urologists and andrologists appointed by the EAU Guidelines Committee.
      Previous recommendations based on the older literature on this subject were taken
      into account. Levels of evidence and grade of guideline recommendations were
      added, modified from the Oxford Centre for Evidence-based Medicine Levels of
      Evidence. EVIDENCE SUMMARY: These EAU guidelines are a short comprehensive
      overview of the updated guidelines of male infertility as recently published by
      the EAU (http://www.uroweb.org/guidelines/online-guidelines/), and they are also
      available in the National Guideline Clearinghouse (http://www.guideline.gov/).

PMID- 22591629
TI  - Re: Xiao-Dong Jin, Simone Roethlisberger, Fiona C. Burkhard, Frederic
      Birkhaeuser, Harriet C. Thoeny, Urs E. Studer. Long-term renal function after
      urinary diversion by ileal conduit or orthotopic ileal bladder substitution. Eur
      Urol 2012;61:491-7.

PMID- 22591630
TI  - Safety study of umbilical single-port laparoscopic radical prostatectomy with a
      new DuoRotate system.
AB  - BACKGROUND: Laparoendoscopic single-site (LESS) radical prostatectomy (RP) has
      been performed through different approaches. A new DuoRotate manual system
      developed by Richard Wolf (KeyPort; Richard Wolf GmbH, Knittlingen, Germany) can
      be applied to RP. OBJECTIVES: Our aim was to describe the surgical technique and
      report early outcomes of KeyPort LESS-RP to determine if this procedure is
      feasible and safe. DESIGN, SETTING, AND PARTICIPANTS: Prospective study performed
      between October 2011 and January 2012 to standardize LESS-RP. A total of 31
      procedures were performed (10 with and 21 without neurovascular preservation, 8
      with and 23 without pelvic lymph node dissection). SURGICAL PROCEDURE: LESS-RP
      was performed using the methods outlined in the manuscript. All patients
      underwent LESS RP by the same surgical team. Access was achieved via a tri
      channel reusable KeyPort and one 3.5-mm extra port to facilitate urethrovesical
      anastomosis and drainage extraction. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: Preoperative, perioperative, and pathologic outcomes data are
      presented. RESULTS AND LIMITATIONS: The mean age of the patients was 64 yr; mean
      body mass index: 30.7 kg/m(2); mean prostate-specific antigen level: 7 ng/ml;
      mean operative time: 207 min; and mean estimated blood loss: 258 ml. The average
      length of stay was 2.9 d and visual analog pain score (range: 0 [no pain] to 10)
      at day 2 was 1.2. Five focal positive margins (16.7%) were encountered (4.4% for
      pT2 and 57.1% for pT3). Five cases (16.7%) were pT2a, 3 (10%) were pT2b, 15 (50%)
      were pT2c, and 7 (23.3%) were pT3a. Lymph node dissection results were negative
      in all patients. Major complications occurred in two patients (6.5%) (hypercapnia
      with respiratory acidosis and rectourethral fistula) and minor complications in
      four (12.9%) (atrial fibrillation, orchitis, transfusion, and vomiting). No case
      required additional analgesia. Incision was totally hidden in the umbilicus.
      Study limitations included short follow-up (mean: 20.2 +/- 4.1 wk), premature
      functional data, and absence of a comparative cohort. CONCLUSIONS: The KeyPort
      system allows performance of umbilical RP with few complications, a low positive
      margin rate, excellent aesthetic results, and very low postoperative pain levels.

PMID- 22591632
TI  - Do all anesthesiologists have a "sell by" date?

PMID- 22591631
TI  - Neurovascular structure-adjacent frozen-section examination (NeuroSAFE) increases
      nerve-sparing frequency and reduces positive surgical margins in open and robot
      assisted laparoscopic radical prostatectomy: experience after 11,069 consecutive
      patients.
AB  - BACKGROUND: Intraoperative frozen-section analysis allows real-time histologic
      assessment of surgical margins (SMs) and identification of candidates for nerve
      sparing (NS) procedures. OBJECTIVE: To examine the efficacy and oncologic safety
      of a systematic neurovascular structure-adjacent frozen-section examination
      (NeuroSAFE) during NS radical prostatectomy (RP). DESIGN, SETTING, AND
      PARTICIPANTS: From January 2002 to June 2011, 11 069 consecutive RPs were
      performed at the University Medical Center Hamburg-Eppendorf. Of these, 5392
      (49%) were conducted with NeuroSAFE. SURGICAL PROCEDURE: Our NeuroSAFE approach
      included the whole laterorectal circumference of the prostate to determine the SM
      status of the complete neurovascular tissue-corresponding prostatic surface.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The impact of NeuroSAFE on NS
      frequency, SM status, and biochemical recurrence (BCR) was analyzed by chi-square
      test, and by Kaplan-Meier analyses in propensity score-based matched cohorts.
      RESULTS AND LIMITATIONS: Positive SMs (PSMs) were detected in 1368 (25%)
      NeuroSAFE RPs, leading to a secondary resection of the ipsilateral neurovascular
      tissue. Secondary wide resection resulted in conversion to a definitive negative
      SM (NSM) status in 1180 (86%) patients. In NeuroSAFE RPs, frequency of NS was
      significantly higher (all stages: 97% vs 81%; pT2: 99% vs 92%; pT3a: 94% vs 72%;
      pT3b: 88% vs 40%; p<0.0001) and PSM rates were significantly lower (all stages:
      15% vs 22%; pT2: 7% vs 12%; pT3a: 21% vs 32%; p<0.0001) than in the matched non
      NeuroSAFE RPs. In propensity score-based comparisons, NeuroSAFE had no negative
      impact on BCR (pT2, p=0.06; pT3a, p=0.17, pT3b, p=0.99), and BCR-free survival of
      patients with conversion to NSM did not differ significantly from patients with
      primarily NSM (pT2, p=0.16; pT3, p=0.26). The accuracy of our NeuroSAFE approach
      was 97% with a false-negative rate of 2.5%. The major limitations of this study
      are its retrospective nature and relatively short follow-up. CONCLUSIONS:
      NeuroSAFE enables real-time histologic monitoring of the oncologic safety of a NS
      procedure. Systematic NeuroSAFE significantly increases NS frequencies and
      reduces PSMs. Patients with a NeuroSAFE-detected PSM could be converted to a
      prognostically more favorable NSM status by secondary wide resection.

PMID- 22591633
TI  - A public health enforcement initiative to combat underage drinking using
      Emergency Medical Services call data.
AB  - OBJECTIVE: The objective of this study was to determine whether Emergency Medical
      Services (EMS) records can identify bars that serve a disproportionate number of
      minors, and if government officials will use this data to direct underage drinker
      enforcement efforts. METHODS: Emergency Medical Services call logs to all bars in
      the study area were cross-referenced with a local hospital's records. The records
      of patients with alcohol-related complaints were analyzed. Outlier bars were
      identified, and presented to government officials who completed a survey to
      assess if this information would prompt new enforcement efforts. RESULTS:
      Emergency Medical Services responded to 149 establishments during the study
      period. Eighty-four responses were distributed across six bars, and 78 were
      matched with the hospital's records. Fifty-one patients, 18 (35%) of whom were
      underage, were treated for alcohol intoxication, with 46% of the cases
      originating from four bars. Government officials found the information useful,
      and planned to initiate new operations based on the information. CONCLUSIONS:
      Alcohol consumption by minors can lead to life-long abuse, with high personal,
      financial, and societal costs. Emergency Medical Services response data and
      hospital records can be used to identify bars that allow underage drinking, which
      is useful in directing law enforcement efforts.

PMID- 22591634
TI  - Relationship between lymphocytopenia and circulating tumor cells as prognostic
      factors for overall survival in metastatic breast cancer.
AB  - INTRODUCTION: Lymphocytopenia and circulating tumor cells (CTCs) have been
      reported as independent prognostic factors for overall survival (OS) in
      metastatic breast cancer (MBC), and both have been associated with bone
      metastases. Our objective was to compare the prognostic significance of
      lymphocytopenia, CTC count, and extensive bone metastases (> 2 lesions) assessed
      by fluorine-18 ((18)F) fluorodeoxyglucose positron emission tomography/computed
      tomography (FDG-PET/CT) in patients with MBC. PATIENTS AND METHODS: This is a
      retrospective study that included patients with MBC who were starting a new line
      of systemic therapy. The study population consisted of patients treated at the
      University of Texas MD Anderson Cancer Center between 2004 and 2008 for whom
      baseline CTC count, lymphocyte counts, and FDG-PET/CT scans were available.
      Patients were stratified according to estrogen receptor status (positive vs.
      negative), human epidermal growth factor receptor 2 (HER2) status (amplified vs.
      constitutive), baseline CTC counts per 7.5 mL of blood (< 5 CTCs/7.5 mL of blood
      vs. >= 5 CTCs/7.5 mL of blood), lymphocytopenia (< 1000 vs. >= 1000/MUL), and
      extensive bone metastases (> 2 vs. <= 2 lesions). RESULTS: In 195 assessable
      patients, the median OS was 27 months (range, 1 to > 45 months). In multivariate
      analysis, lymphocytopenia, >= 5 CTCs/7.5 mL of blood, estrogen receptor status,
      and line of therapy were the only predictive factors for progression-free
      survival (PFS) (2P = .001, 2P = .032, 2P = .029, and 2P = .002, respectively) and
      OS (2P = .001, 2P = .009, 2P = .004, and 2P = .024, respectively). CONCLUSION:
      CTC measurement and lymphocytopenia are independent prognostic factors for PFS
      and OS in patients with MBC.

PMID- 22591635
TI  - SOCS3 in immune regulation of inflammatory bowel disease and inflammatory bowel
      disease-related cancer.
AB  - Inflammatory bowel disease (IBD) has unclear pathogenesis and it is related to
      the increasing risk of developing colorectal cancer (CRC). Recent studies have
      uncovered the molecular mechanism of intracellular signaling pathways of
      inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interferon
      (IFN)-gamma and interleukin (IL)-6. The major transcription factors including
      STAT3 have been shown to play a major role in transmitting inflammatory cytokine
      signals to the nucleus. The suppressors of cytokine signaling (SOCS) 3 protein is
      the key physiological regulators of cytokine-mediated STAT3 signaling. As such it
      influences the development of inflammatory and malignant disorders like this
      associated with IBD. Here we review the complex function of SOCS3 in innate and
      adaptive immunity, different cell types (macrophages, neutrophils, dendritic
      cells, B cells, T cells and intestinal epithelial cells) and the role of SOCS3 on
      the pathogenesis of inflammatory bowel disease (IBD) and IBD-related cancer.
      Finally, we explore how this knowledge may open novel avenues for the rational
      treatment of IBD and IBD-related cancer.

PMID- 22591636
TI  - Factors associated with edentulousness in an elderly population in Valencia
      (Spain).
AB  - OBJECTIVE: To determine the prevalence of edentulism and its association with
      various socioeconomic factors and oral health habits in the population aged 65-74
      years old in the region of Valencia. METHODS: A cross sectional study was
      designed. Thirty-four primary health centers and five nursing homes were chosen
      at random in the region of Valencia (10-15 voluntary participants per sampling
      point). Clinical examinations were carried out by three calibrated dentists
      (kappa>0.85) in the same centers. The total sample consisted of 531 individuals
      (235 men and 296 women). RESULTS: The percentage of toothlessness was 20.7% and
      the mean number of natural teeth present was 14.92. The prevalence of edentulism
      was significantly higher (p <0.05) in men, institutionalized persons, those with
      no schooling, those with poor oral hygiene, those who visited the dentist
      regularly and those living in peri-urban/rural areas. In a multivariate logistic
      regression model with edentulism as the dependent variable, the following factors
      were identified as significant independent variables: institutionalization (odds
      ratio [OR]=2.88), poor oral hygiene (OR=2.35), regular visits to the dentist
      (OR=2.34) and age (OR=1.19). CONCLUSION: Edentulousness is a complex phenomenon
      that involves distinct social and economic factors.

PMID- 22591638
TI  - Modeling technology innovation: how science, engineering, and industry methods
      can combine to generate beneficial socioeconomic impacts.
AB  - BACKGROUND: Government-sponsored science, technology, and innovation (STI)
      programs support the socioeconomic aspects of public policies, in addition to
      expanding the knowledge base. For example, beneficial healthcare services and
      devices are expected to result from investments in research and development (R&D)
      programs, which assume a causal link to commercial innovation. Such programs are
      increasingly held accountable for evidence of impact-that is, innovative goods
      and services resulting from R&D activity. However, the absence of comprehensive
      models and metrics skews evidence gathering toward bibliometrics about research
      outputs (published discoveries), with less focus on transfer metrics about
      development outputs (patented prototypes) and almost none on econometrics related
      to production outputs (commercial innovations). This disparity is particularly
      problematic for the expressed intent of such programs, as most measurable
      socioeconomic benefits result from the last category of outputs. METHODS: This
      paper proposes a conceptual framework integrating all three knowledge-generating
      methods into a logic model, useful for planning, obtaining, and measuring the
      intended beneficial impacts through the implementation of knowledge in practice.
      Additionally, the integration of the Context-Input-Process-Product (CIPP) model
      of evaluation proactively builds relevance into STI policies and programs while
      sustaining rigor. RESULTS: The resulting logic model framework explicitly traces
      the progress of knowledge from inputs, following it through the three knowledge
      generating processes and their respective knowledge outputs (discovery,
      invention, innovation), as it generates the intended socio-beneficial impacts. It
      is a hybrid model for generating technology-based innovations, where best
      practices in new product development merge with a widely accepted knowledge
      translation approach. Given the emphasis on evidence-based practice in the
      medical and health fields and "bench to bedside" expectations for knowledge
      transfer, sponsors and grantees alike should find the model useful for planning,
      implementing, and evaluating innovation processes. CONCLUSIONS: High-cost/high
      risk industries like healthcare require the market deployment of technology-based
      innovations to improve domestic society in a global economy. An appropriate
      balance of relevance and rigor in research, development, and production is
      crucial to optimize the return on public investment in such programs. The
      technology-innovation process needs a comprehensive operational model to
      effectively allocate public funds and thereby deliberately and systematically
      accomplish socioeconomic benefits.

PMID- 22591639
TI  - Estimation of optimal insertion angle in a mammalian outer hair cell
      stereocilium.
AB  - Optimal insertion angle of mammalian stereocilia is estimated from the finite
      element analysis of the tip motion of outer hair cells (OHCs) stereocilia. The
      OHC stereocilia motion in the acousticolateral system appears to result in the
      mechanoelectrical transduction channels. Deflection of the hair bundle towards
      the tallest row of stereocilia causes increased probability of opening of ion
      channels. In this work, we focus on one of the physical features of the OHC
      stereocilium, the initial insertion angle of the tallest row into the tectorial
      membrane (TM), and its effects on the stereocilia's deflection motion. A three
      dimensional model was built for the tallest stereocilium and the TM at the region
      where the best frequency was 500Hz. The mechanical interactions between the
      embedded stereocilia and the TM have been implemented into the finite element
      simulation. We found that, the optimum insertion angle of the tallest
      stereocilium into the TM was 69.8 degrees , where the stereocilium is maximally
      deflected. This quantity is consistent with the histological observation obtained
      from the literature.

PMID- 22591637
TI  - FLJ10540 is associated with tumor progression in nasopharyngeal carcinomas and
      contributes to nasopharyngeal cell proliferation, and metastasis via
      osteopontin/CD44 pathway.
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) is well-known for its highly
      metastatic characteristics, but little is known of its molecular mechanisms. New
      biomarkers that predict clinical outcome, in particular the ability of the
      primary tumor to develop metastatic tumors are urgently needed. The aim of this
      study is to investigate the role of FLJ10540 in human NPC development. METHODS: A
      bioinformatics approach was used to explore the potentially important regulatory
      genes involved in the growth/metastasis control of NPC. FLJ10540 was chosen for
      this study. Two co-expression strategies from NPC microarray were employed to
      identify the relationship between FLJ10540 and osteopontin. Quantitative-RT-PCR,
      immunoblotting, and immunohistochemistry analysis were used to investigate the
      mRNA and protein expression profiles of FLJ10540 and osteopontin in the normal
      and NPC tissues to confirm microarray results. TW01 and Hone1 NPC cells with
      overexpression FLJ10540 or siRNA to repress endogenous FLJ10540 were generated by
      stable transfection to further elucidate the molecular mechanisms of FLJ10540
      elicited cell growth and metastasis under osteopontin stimulation. RESULTS: We
      found that osteopontin expression exhibited a positive correlation with FLJ10540
      in NPC microarray. We also demonstrated comprehensively that FLJ10540 and
      osteopontin were not only overexpressed in NPC specimens, but also significantly
      correlated with advanced tumor and lymph node-metastasis stages, and had a poor 5
      year survival rate, respectively. Stimulation of NPC parental cells with
      osteopontin results in an increase in FLJ10540 mRNA and protein expressions.
      Functionally, FLJ10540 transfectant alone, or stimulated with osteopontin,
      exhibited fast growth and increased metastasis as compared to vehicle control
      with or without osteopontin stimulation. Conversely, knockdown of FLJ10540 by
      siRNA results in the suppression of NPC cell growth and motility. Treatment with
      anti-CD44 antibodies in NPC parental cells not only resulted in a decrease of
      FLJ10540 protein, but also affected the abilities of FLJ10540-elicited cell
      growth and motility in osteopontin stimulated-NPC cells. CONCLUSIONS: These
      findings suggest that FLJ10540 may be critical regulator of disease progression
      in NPC, and the underlying mechanism may involve in the osteopontin/CD44 pathway.

PMID- 22591640
TI  - Aortic thrombosis in dogs: presentation, therapy, and outcome in 26 cases.
AB  - OBJECTIVES: The pathogenesis and presentation of aortic thrombosis (AT) in dogs
      is not well characterized and an effective antithrombotic therapy for AT in dogs
      has not been identified. Our goal is to report the clinical presentation and
      results of therapies in dogs with AT. ANIMALS: Twenty-six client-owned dogs.
      METHODS: Retrospective review of medical records of dogs diagnosed with AT
      between 2003 and 2010. RESULTS: Twenty-six dogs had an apparent primary mural
      aortic thrombus. None had structural heart disease at diagnosis. Twenty dogs were
      ambulatory with varying degrees of pelvic limb dysfunction. Duration of
      ambulatory dysfunction was 7.8 weeks (range 1 day-52 weeks). A majority of dogs
      (58%) had no concurrent conditions at diagnosis. Fourteen dogs were treated with
      a standard warfarin protocol for a median period of 22.9 months (range 0.5-53
      months). Ambulatory function improved in all dogs treated with warfarin. Time
      until clinical improvement was 13.9 days (range 2-49 days). Dogs treated with
      warfarin did not become non-ambulatory, die or undergo euthanasia related to AT,
      or have a known serious hemorrhagic event. CONCLUSIONS: The pathogenesis of AT in
      dogs is distinct from that of aortic thromboembolism (ATE) in cats. Aortic
      thrombosis in dogs is more likely to involve local thrombosis in the distal aorta
      with embolization to the arteries of the pelvic limb resulting in chronic
      progressive ambulatory dysfunction. Chronic warfarin administration is well
      tolerated and appears to be an effective short-term and long-term therapy for
      dogs with AT.

PMID- 22591641
TI  - The interplay of mitochondria with calcium: an historical appraisal.
AB  - Indirect findings in the 1950s had indicated that mitochondria could accumulate
      Ca(2+), but only in 1961 isolated mitochondria were directly shown to take it up
      in a process driven by the activity of the respiratory chain or by the hydrolysis
      of added ATP. The uptake of Ca(2+) could be accompanied by the simultaneous
      uptake of inorganic phosphate, leading to the precipitation of hydroxyapatite in
      the matrix and to the effective buffering of the free Ca(2+) concentration in it.
      The uptake of Ca(2+) occurred via an electrophoretic uniporter that has been
      molecularly identified only recently. Ca(2+) was then released through a
      Na(+)/Ca(2+) exchanger that has also been identified very recently (a H(+)/Ca(2+)
      antiporter has also been described in some mitochondrial types). In the matrix
      two TCA cycle dehydrogenases and pyruvate dehydrogenase phosphate phosphatase
      were found to be regulated by Ca(2+), providing a rationale for the Ca(2+)
      cycling process. The affinity of the uptake uniporter was found to be too low to
      efficiently regulate Ca(2+) in the low to mid nM concentration in the cytosol.
      However, a number of findings showed that energy linked transport of Ca(2+) did
      nevertheless occur in mitochondria in situ. The enigma was solved in the 1990s,
      when it was found that perimitochondrial Ca(2+) pools are created by the
      discharge of Ca(2+) from vicinal endoplasmic reticulum stores in which the
      concentration of Ca(2+) is high enough to satisfy the poor affinity of the
      uniporter. Thus, mitochondria have now regained a key role in the regulation of
      cytosolic Ca(2+) (not only of their own internal Ca(2+)).

PMID- 22591642
TI  - Spatio-temporal aspects, pathways and actions of Ca(2+) in surfactant secreting
      pulmonary alveolar type II pneumocytes.
AB  - The type II cell of the pulmonary alveolus is a polarized epithelial cell that
      secretes surfactant into the alveolar space by regulated exocytosis of lamellar
      bodies (LBs). This process consists of multiple sequential steps and is
      correlated to elevations of the cytoplasmic Ca(2+) concentration ([Ca(2+)](c))
      required for extended periods of secretory activity. Both chemical (purinergic)
      and mechanical (cell stretch or exposure to an air-liquid interface) stimuli give
      rise to complex Ca(2+) signals (such as Ca(2+) peaks, spikes and plateaus) that
      differ in shape, origin and spatio-temporal behavior. This review summarizes
      current knowledge about Ca(2+) channels, including vesicular P2X4 purinoceptors,
      in type II cells and associated signaling cascades within the alveolar
      microenvironment, and relates stimulus-dependent activation of these pathways
      with distinct stages of surfactant secretion, including pre- and postfusion
      stages of LB exocytosis.

PMID- 22591643
TI  - A strategy to increase adoption of locally-produced, ceramic cookstoves in rural
      Kenyan households.
AB  - BACKGROUND: Exposure to household air pollutants released during cooking has been
      linked to numerous adverse health outcomes among residents of rural areas in low
      income countries. Improved cookstoves are one of few available interventions, but
      achieving equity in cookstove access has been challenging. Therefore, innovative
      approaches are needed. To evaluate a project designed to motivate adoption of
      locally-produced, ceramic cookstoves (upesi jiko) in an impoverished, rural
      African population, we assessed the perceived benefits of the cookstoves (in
      monetary and time-savings terms), the rate of cookstove adoption, and the equity
      of adoption. METHODS: The project was conducted in 60 rural Kenyan villages in
      2008 and 2009. Baseline (n = 1250) and follow-up (n = 293) surveys and a stove
      tracking database were analyzed. RESULTS: At baseline, nearly all respondents
      used wood (95%) and firepits (99%) for cooking; 98% desired smoke reductions.
      Households with upesi jiko subsequently spent <100 Kenyan Shillings/week on
      firewood more often (40%) than households without upesi jiko (20%) (p = 0.0002).
      There were no significant differences in the presence of children <2 years of age
      in households using upesi jiko (48%) or three-stone stoves (49%) (p = 0.88);
      children 2-5 years of age were less common in households using upesi jiko versus
      three-stone stoves (46% and 69%, respectively) (p = 0.0001). Vendors installed
      1,124 upesi jiko in 757 multi-family households in 18 months; 68% of these
      transactions involved incentives for vendors and purchasers. Relatively few
      (<10%) upesi jiko were installed in households of women in the youngest age
      quartile (<22 years) or among households in the poorest quintile. CONCLUSIONS:
      Our strategy of training of local vendors, appropriate incentives, and product
      integration effectively accelerated cookstove adoption into a large number of
      households. The strategy also created opportunities to reinforce health messages
      and promote cookstoves sales and installation. However, the project's overall
      success was diminished by inequitable and incomplete adoption by households with
      the lowest socioeconomic status and young children present. Additional
      evaluations of similar strategies will be needed to determine whether our
      strategy can be applied equitably elsewhere, and whether reductions in fuel use,
      household air pollution, and the incidence of respiratory diseases will follow
      adoption of improved cookstoves.

PMID- 22591644
TI  - Diagnostic clues and subsequent examinations that detected small pancreatic
      cancer.
AB  - BACKGROUND/AIMS: Our aim was to investigate how 2cm or smaller pancreatic cancers
      were detected successfully in recent years. METHODOLOGY: Diagnostic clues and
      subsequent examinations that detected 15 histologically confirmed 2 cm or smaller
      pancreatic cancers were reviewed. RESULTS: Diagnostic clues were imaging findings
      in 6 patients, symptoms in 5 and laboratory data in 4. Six of 8 patients who had
      risk factors of pancreatic cancer such as pancreatic cyst, dilated main
      pancreatic duct, pancreatitis, or diabetes had been followed-up by imaging and
      laboratory examinations. Five patients with extrapancreatic disease had been
      followed-up chiefly by laboratory examinations. The remaining 2 had neither of
      them. Detectabilities of pancreatic mass in US, CT and EUS were 89%, 67% and
      100%, respectively; those of pancreatic mass and/or dilated main pancreatic duct
      were 100% in all three modalities. Cytological examination revealed
      adenocarcinoma preoperatively in 14 patients (93%). CONCLUSIONS: Small pancreatic
      cancer of 2 cm or smaller were suggested by symptoms, laboratory data, or imaging
      examinations. They were confirmed by further examinations including cytology.

PMID- 22591645
TI  - Elevation of platelet count in patients with colorectal cancer predicts tendency
      to metastases and poor prognosis.
AB  - BACKGROUNDS/AIMS: Thrombocytosis had been found to be associated with tumor
      metastasis and poor prognosis in malignant tumors including colorectal cancer
      (CRC). In the present study, we investigated the relationship between the
      platelet and the biological features in patients with CRC in China. METHODOLOGY:
      The correlation of platelet counts of 150 cases with CRC with their
      clinicopathological characteristics was explored. Furthermore, the survival
      impact of preoperative platelet count was also investigated. RESULTS:
      Statistically significant correlations between the platelet count and the lymph
      node and distance metastasis (p=0.016 and 0.014), vascular and perinural invasion
      (p=0.025 and 0.016) as well as TNM clinical stages (p=0.014) except for the age,
      gender and grades (p=0.245, 0.276 and 0.324, respectively) were found. In
      addition, 5-year survival of patients with high platelet count and normal
      platelet count were 13.30% and 56.30%, respectively (p=0.000). Meanwhile,
      concurrent with lymph node and distance metastasis, perinural invasion and
      clinical stages (p=0.000, 0.022, 0.034 and 0.000), platelet count (p=0.010) was
      also found to be an independent prognostic factor in CRC in our study through
      multivariate analysis. CONCLUSIONS: Elevated platelet might play some role in the
      progress of CRC and preoperative platelet count might be a prognostic indicator
      in the CRC patients.

PMID- 22591646
TI  - Diagnostic role of endoscopic ultrasonography-guided fine needle aspiration of
      gallbladder lesions.
AB  - BACKGROUND/AIMS: Endoscopic ultrasonography-guided fine needle aspiration (EUS
      FNA) is a well-established diagnostic technique for examining various organs of
      the gastrointestinal tract and pancreas, but little is known about its use in the
      diagnostic work-up of GB lesions. The objective of this retrospective study was
      to evaluate the efficacy of EUS-FNA of GB lesions. METHODOLOGY: Twenty-eight
      patients who underwent EUS-FNA for evaluation of GB lesions were enrolled. The
      pathological results and complications were assessed. RESULTS: EUS-FNA of GB was
      performed in 13 patients and that of enlarged lymph nodes was done in 18. Of the
      13 GB lesions sampled by EUS-FNA, 10 were diagnosed as malignant and 3 were
      negative for malignant cells. Of the latter 3, two were false negatives for
      malignancy. All 14 metastatic lymphadenopathy cases were diagnosed with EUS-FNA
      of lymph nodes. EUS-FNA could differentiate adenocarcinomas and other malignant
      diseases. Cholecystitis occurred in one patient after EUS-FNA of the GB.
      CONCLUSIONS: EUS-FNA is a feasible, safe and reliable method for obtaining
      samples from GB lesions. EUS-FNA of lymph nodes is complementary to EUS-FNA of
      the GB and provides nodal stage as well as histological diagnosis.

PMID- 22591648
TI  - Evaluation of synthetic acridones and 4-quinolinones as potent inhibitors of
      cathepsins L and V.
AB  - Cathepsins, also known as lysosomal cysteine peptidases, are members of the
      papain-like peptidase family, involved in different physiological processes. In
      addition, cathepsins are implicated in many pathological conditions. This report
      describes the synthesis and evaluation of a series of N-arylanthranilic acids,
      acridones, and 4-quinolinones as inhibitors of cathepsins V and L. The kinetics
      revealed that compounds of the classes of acridones are reversible competitive
      inhibitors of the target enzyme with affinities in the low micromolar range. They
      represent promising lead candidates for the discovery of novel competitive
      cathepsin inhibitors with enhanced selectivity and potency. On the other hand, 4
      quinolinones were noncompetitive inhibitors and N-arylanthranilic acids were
      uncompetitive inhibitors.

PMID- 22591647
TI  - The intravascular volume effect of Ringer's lactate is below 20%: a prospective
      study in humans.
AB  - INTRODUCTION: Isotonic crystalloids play a central role in perioperative fluid
      management. Isooncotic preparations of colloids (for example, human albumin or
      hydroxyethyl starch) remain nearly completely intravascular when infused to
      compensate for acute blood losses. Recent data were interpreted to indicate a
      comparable intravascular volume effect for crystalloids, challenging the
      occasionally suggested advantage of using colloids to treat hypovolemia. General
      physiological knowledge and clinical experience, however, suggest otherwise.
      METHODS: In a prospective study, double-tracer blood volume measurements were
      performed before and after intended normovolemic hemodilution in ten female
      adults, simultaneously substituting the three-fold amount of withdrawn blood with
      Ringer's lactate. Any originated deficits were substituted with half the volume
      of 20% human albumin, followed by a further assessment of blood volume. To assess
      significance between the measurements, repeated measures analysis of variance
      (ANOVA) according to Fisher were performed. If significant results were shown,
      paired t tests (according to Student) for the singular measurements were taken. P
      < 0.05 was considered to be significant. RESULTS: A total of 1,097 +/- 285 ml of
      whole blood were withdrawn (641 +/- 155 ml/m(2) body surface area) and
      simultaneously replaced by 3,430 +/- 806 ml of Ringer's lactate. All patients
      showed a significant decrease in blood volume after hemodilution (-459 +/- 185
      ml; P < 0.05) that did not involve relevant hemodynamical changes, and a
      significant increase in interstitial water content (+2,157 +/- 606 ml; P < 0.05).
      The volume effect of Ringer's lactate was 17 +/- 10%. The infusion of 245 +/- 64
      ml of 20% human albumin in this situation restored blood volume back to baseline
      values, the volume effect being 184 +/- 63%. CONCLUSIONS: Substitution of
      isolated intravascular deficits in cardiopulmonary healthy adults with the three
      fold amount of Ringer's lactate impedes maintenance of intravascular
      normovolemia. The main side effect was an impressive interstitial fluid
      accumulation, which was partly restored by the intravenous infusion of 20% human
      albumin. We recommend to substitute the five-fold amount of crystalloids or to
      use an isooncotic preparation in the face of acute bleeding in patients where
      edema prevention might be advantageous.

PMID- 22591649
TI  - Polymyalgia rheumatica following robotic radical prostatectomy.
AB  - INTRODUCTION: Polymyalgia rheumatica (PMR) is an inflammatory syndrome of unknown
      etiology has also been associated with concurrent malignancy. Here we report PMR
      occurring de novo in a man following successful robotic radical prostatectomy.
      PRESENTATION OF CASE: A 67-year-old gentleman underwent uneventful robotic
      assisted radical prostatectomy with complete excision of a T2(C) Gleason 7 tumour
      and a post-operative undetectable PSA. Three weeks after surgery he developed
      pain and weakness of the upper arms requiring increasing doses of opioids.
      Assessment identified a grossly elevated ESR and CRP consistent with a clinical
      diagnosis of PMR. Treatment with oral steroids led to a rapid resolution of
      symptoms. DISCUSSION: There have been reported cases of polymyalgia rheumatica
      occurring following surgical procedures but not with robotic prostate surgery. It
      has been proposed that surgical tissue injury can cause a release of inflammatory
      markers. Surgical stress-related sympathetic activation can also stimulate
      lymphocyte dependent inflammatory reactions by modulation of cytokine production
      and lymphocyte expressed adrenergic receptors. CONCLUSION: We present here the
      first reported case of PMR developing acutely after radical robotic
      prostatectomy. It is possible that the surgical procedure in this case had
      triggered polymyalgia rheumatica possibly through activation of immune-mediated
      systemic inflammatory responses.

PMID- 22591650
TI  - A redundant resource: a pre-planned casualty clearing station for a FIFA 2010
      Stadium in Durban.
AB  - This report details the background, planning, and establishment of a mass
      casualty management area for the Durban Moses Mabhida Stadium at the Natal
      Mounted Rifles base, by the Department of Health and the eThekwini Fire and
      Rescue Service, for the Federation Internationale de Football Association (FIFA)
      2010 Soccer World Cup. The report discusses the use of the site during the seven
      matches played at that stadium, and details the aspects of mass-gathering major
      incident site planning for football (soccer). The area also was used as a
      treatment area for other single patient incidents outside of the stadium, but
      within the exclusion perimeter, and the 22 patients treated by the Casualty
      Clearing Station (CCS) team are described and briefly discussed. A site-specific
      patient presentation rate of 0.48 per 10,000 and transport-to-hospital rate
      (TTHR) of 0.09/10,000 are reported. Lessons learned and implications for future
      event planning are discussed in the light of the existing literature.

PMID- 22591652
TI  - Contact urticaria induced by hydrolyzed wheat protein in cosmetic cream.

PMID- 22591651
TI  - Effects of combined antiretroviral therapy on B- and T-cell release from
      production sites in long-term treated HIV-1+ patients.
AB  - BACKGROUND: The immune system reconstitution in HIV-1- infected patients
      undergoing combined antiretroviral therapy is routinely evaluated by T-cell
      phenotyping, even though the infection also impairs the B-cell mediated immunity.
      To find new laboratory markers of therapy effectiveness, both B- and T- immune
      recovery were evaluated by means of a follow-up study of long-term treated HIV-1-
      infected patients, with a special focus on the measure of new B- and T-lymphocyte
      production. METHODS: A longitudinal analysis was performed in samples obtained
      from HIV-1-infected patients before therapy beginning and after 6, 12, and 72
      months with a duplex real-time PCR allowing the detection of K-deleting
      recombination excision circles (KRECs) and T-cell receptor excision circles
      (TRECs), as measures of bone-marrow and thymic output, respectively. A cross
      sectional analysis was performed to detect B- and T-cell subsets by flow
      cytometry in samples obtained at the end of the follow-up, which were compared to
      those of untreated HIV-1-infected patients and uninfected controls. RESULTS: The
      kinetics and the timings of B- and T-cell release from the bone marrow and thymus
      during antiretroviral therapy were substantially different, with a decreased B
      cell release and an increased thymic output after the prolonged therapy. The
      multivariable regression analysis showed that a longer pre-therapy infection
      duration predicts a minor TREC increase and a major KREC reduction. CONCLUSIONS:
      The quantification of KRECs and TRECs represents an improved method to monitor
      the effects of therapies capable of influencing the immune cell pool composition
      in HIV-1-infected patients.

PMID- 22591653
TI  - Primary cutaneous angioplasmocellular hyperplasia.

PMID- 22591654
TI  - In vivo reflectance confocal microscopy for early diagnosis of nonmelanoma skin
      cancer.
AB  - Reflectance confocal microscopy (RCM) is a novel tool for noninvasive in vivo
      diagnosis of nonmelanoma skin cancer at high resolution. Given the excellent
      correlation that has been demonstrated between RCM findings and routine
      histology, clinicians using this imaging technique can establish an immediate
      diagnosis. Multiple studies have evaluated the use of RCM in melanoma and
      nonmelanoma skin cancer and have demonstrated high sensitivity and specificity
      rates. We discuss the applicability of RCM for the early diagnosis of NMSC and
      discuss other clinical applications of this emerging technique.

PMID- 22591655
TI  - Cardiovascular Risk and Psoriasis: the Role of Biologic Therapy.
AB  - One of the most clinically important aspects of recent advances in our
      understanding of psoriasis has been the detection of an association between this
      disease and an increased prevalence of cardiovascular risk factors. This increase
      in prevalence is, in turn, linked to a greater risk of morbidity and mortality
      related to acute myocardial infarction, cerebrovascular accident, and peripheral
      arterial disease. The chronic systemic inflammation present in psoriasis could
      explain why moderate to severe psoriasis is an independent risk factor for
      cardiovascular disease. The introduction of biologic therapies has greatly
      improved the expectations of treatment as well as the long-term control of
      psoriasis, and there is epidemiological evidence that these therapies may lower
      cardiovascular risk in psoriasis as they do in rheumatoid arthritis. Caution
      should, however, be exercised when prescribing biologic drugs in this setting,
      because adverse effects have been reported in association with the use of tumor
      necrosis factor inhibitors in patients with advanced congestive heart failure.
      Furthermore, a numerical imbalance (without statistical significance) between the
      groups receiving the biologic drug and the placebo groups was recently observed
      in the incidence of major cardiovascular events (nonfatal myocardial infarction
      and cerebrovascular accident and cardiovascular death) during the controlled
      periods of clinical trials of briakinumab and ustekinumab, 2 monoclonal
      antibodies that target the p40 subunit shared by IL 12 and IL-23. We review the
      current scientific evidence on this topic.

PMID- 22591656
TI  - Improvement of genetic stability in lymphocytes from Fanconi anemia patients
      through the combined effect of alpha-lipoic acid and N-acetylcysteine.
AB  - Fanconi Anemia (FA) is a rare genetic disorder, characterized by progressive bone
      marrow failure and increased predisposition to cancer. Despite being highly
      heterogeneous, all FA patients are hypersensitive to alkylating agents, in
      particular to 1,2:3,4-diepoxybutane (DEB), and to oxidative damage. Recent
      studies point to defective mitochondria in FA cells, which is closely related
      with increased production of reactive oxygen species (ROS) and concomitant
      depletion of antioxidant defenses, of which glutathione is a well-known
      biomarker.The objective of the present work is to evaluate the putative
      protective effect of alpha-lipoic acid (alpha-LA), a mitochondrial protective
      agent, and N-acetylcysteine (NAC), a direct antioxidant and a known precursor for
      glutathione synthesis, in spontaneous and DEB-induced chromosome instability (CI)
      in lymphocyte cultures from FA patients.For that purpose, lymphocyte cultures
      from 15 FA patients and 24 healthy controls were pre-treated with 20 MUM alpha
      LA, 500 MUM NAC and alpha-LA plus NAC at the same concentrations, and some of
      them were exposed to DEB (0.05 MUg/ml). A hundred metaphases per treatment were
      scored to estimate the relative frequency of spontaneous and DEB-induced
      chromosome breakage.The obtained results revealed that a cocktail of alpha-LA and
      NAC can drastically improve the genetic stability in FA lymphocytes in vitro,
      decreasing CI by 60% and 80% in cultures from FA patients and FA mosaic/chimera
      patients, respectively. These results suggest that the studied cocktail can be
      used as a prophylactic approach to delay progressive clinical symptoms in FA
      patients caused by CI, which can culminate in the delay of the progressive bone
      marrow failure and early cancer development.

PMID- 22591657
TI  - Whole blood screening of antibodies using label-free nanoparticle biophotonic
      array platform.
AB  - A gold nanoparticle, localised plasmon array biosensor using light scattering has
      been employed in the detection of allergen-specific antibodies in whole blood and
      sera. The array sensor was functionalized with four different allergens, cat
      dander (Fel d1), dust mite (Der p1), peanut allergen (Ara h1) and dog dander (Can
      f1) and immuno-kinetic assay was performed to detect their respective anti
      allergen IgG antibodies. Specific positive responses to antibodies at a
      concentration of 25 nM were observed for Fel d1, Der p1, and Ara h1 allergens,
      while the Can f1 channel served as a reference control. The sensitivity was
      further enhanced using a secondary anti-IgG detection antibodies to give a limit
      of detection of 2 nM. The results indicate the potential for nanoparticle
      scattering multiplexed arrays to screen unprepared blood samples at point-of-care
      for assays of complex samples such as the whole blood.

PMID- 22591658
TI  - A retrospective study comparing preoperative evaluations and postoperative
      outcomes in paediatric and adult patients undergoing surgical resection for
      refractory epilepsy.
AB  - PURPOSE: To review and compare the preoperative characteristics and postsurgical
      outcomes in paediatric and adult patients who underwent surgical resections from
      2001 to 2009. METHODS: Combined data from noninvasive measures such as ictal
      semiology, interictal/ictal scalp EEGs, MRI and SPECT were utilised to identify
      the epileptogenic zones (EZ). When noninvasive investigations produced
      inconclusive or inconsistent findings, patients underwent intracranial EEG
      monitoring. Resective micro-surgical procedures were conducted according to the
      results of the anatomo-electro-clinical investigations and were carried out to
      remove the EZ. We then followed up 222 paediatric (<=18 years old) and 100 adult
      patients (>=19 years old) for 1-9 years postoperatively. RESULTS: The mean age of
      seizure onset in paediatric group was significantly lower than that in adult
      group. 95 (43%) of the paediatric and 42 (42%) of the adult patients required
      long-term intracranial EEG recording. 54 (24.3%) of the paediatric and 62 (62%)
      of the adult patients were found to have temporal lobe epilepsy (TLE), while 149
      (67.1%) of the paediatric and 37 (37.0%) of the adult patients had extra-temporal
      lobe epilepsy (ETLE) (p=0.000). 19 (8.6%) of the paediatric patients and 1 (1%)
      adult patient had hemispheric lesions (p=0.009). 148 (66.7%) of the paediatric
      and 61 (61.0%) of the adult patients were seizure-free during the follow-up
      period. 17 of 19 (89.5%) children who underwent hemispherectomy were seizure
      free. In both paediatric and adult groups, the surgical outcome for patients with
      TLE was significantly better than that of patients with ETLE (p=0.018 in
      children, p=0.029 in adults). Both the location of EZs and seizure-free ratio
      were significantly different (p<0.001) between the preadolescent (<=12 years old)
      and adolescent (13-18 years old) group. Hippocampal sclerosis was the most common
      pathologic finding in patients with TLE in both groups, and was followed by focal
      cortical dysplasia. In patients with TLE, the proportion of tumour was
      significantly higher in the paediatric than the adult group (25.9% vs. 10%,
      p=0.021). CONCLUSION: Paediatric patients with refractory seizures had more
      extratemporal or hemispheric resectable epileptogenic foci and fewer temporal
      foci than adults. Our study demonstrates that resective surgery is an effective
      and safe early intervention in strictly selected paediatric patients with
      refractory epilepsy.

PMID- 22591659
TI  - Individual insurance benefits to be available under health reform would have cut
      out-of-pocket spending in 2001-08.
AB  - Under the Affordable Care Act, individual health insurance will probably become
      more generous and more like employment-related insurance. Currently, individual
      insurance typically has less generous benefits than employment-related insurance.
      This study compared out-of-pocket spending on health care between individual and
      employment-related insurance, controlling for numerous characteristics such as
      health status. Then it simulated the impact of full implementation of provisions
      of the Affordable Care Act on adults who currently have individual insurance,
      including important subgroups-adults with chronic conditions, the near-elderly
      (ages 55-64), and low-income populations. If adults who had individual insurance
      during 2001-08 had instead had benefits similar to those under the Affordable
      Care Act, their average annual out-of-pocket spending on medical care and drugs
      might have been $280 less. The near-elderly and people with low incomes might
      have saved $589 and $535, respectively. An important improvement would have been
      the reduced probability of incurring very high out-of-pocket spending. The
      likelihood of having out-of-pocket expenditures on care exceeding $6,000 would
      have been reduced for all adults with individual insurance, and the likelihood of
      having expenditures exceeding $4,000 would have been reduced for many.

PMID- 22591660
TI  - Identification of the double-bond position in fatty acid methyl esters by liquid
      chromatography/atmospheric pressure chemical ionisation mass spectrometry.
AB  - Fatty acid methyl esters (FAMEs) were analysed by reversed-phase HPLC coupled
      with atmospheric pressure chemical ionisation (APCI) mass spectrometry. The
      chromatographic separations of the FAMEs were optimised using acetonitrile or
      binary acetonitrile gradients and C18 or C30 columns. The gas-phase reactions of
      acetonitrile and unsaturated FAMEs in the APCI source provided [M+C(3)H(5)N](+.)
      adducts. When fragmented, these adducts yielded diagnostic ions, allowing the
      unambiguous localisation of double bonds. The formation and fragmentation of the
      acetonitrile-related adduct was utilised for the structural characterisation of
      the FAMEs separated by HPLC. The APCI-MS detection of FAMEs encompassed a full
      spectrum scan (providing information on the number of carbons and double bonds)
      and a data-dependent MS/MS scan of the [M+C(3)H(5)N](+.) ions (the position of
      the double bonds). The utility of this approach was demonstrated using a mixture
      of FAMEs from blackcurrant-seed oil. All the unsaturated fatty acids known to
      exist in the sample were correctly identified and several others were newly
      discovered. In terms of sensitivity, HPLC/APCI-MS appeared to be comparable to
      GC/EI-MS.

PMID- 22591661
TI  - Three sensitive assays do not provide evidence for circulating HuD-specific T
      cells in the blood of patients with paraneoplastic neurological syndromes with
      anti-Hu antibodies.
AB  - Anti-Hu antibody-associated paraneoplastic neurological syndromes (Hu-PNSs) are
      severe and often precede the detection of a malignancy, usually small-cell lung
      cancer. In Hu-PNS, it is hypothesized that neuronal cells are destroyed by T
      cells targeted against HuD, a protein expressed by small-cell lung cancer cells
      and neurons. There is only limited evidence for the existence of HuD-specific T
      cells. To detect these T cells in the blood of Hu-PNS patients, we employed 3
      highly sensitive assays that included T cell stimulation with dendritic cells
      (DCs) to specifically expand the number of any HuD-specific T cells. A total of
      17 Hu-PNS patients were tested with 1 or more of the following 3 assays: (1)
      tetramer staining after stimulation of T cells with conventionally generated DCs
      (n = 9), (2) interleukin (IL)-13 enzyme-linked immunosorbent spot (ELISpot; n =
      3), IL-4 and IL-5 and interferon (IFN)-gamma multiplex cytokine bead array (n =
      2) to assay cytokine production by T cells after stimulation with conventionally
      generated DCs, and (iii) IFN-gamma ELISpot and tetramer staining after T cell
      stimulation with accelerated co-cultured DCs (n = 11). No circulating HuD
      specific T cells were found. We suggest that either autoaggressive T cells in Hu
      PNS are not targeted against HuD or that their numbers in the blood are too low
      for detection by highly sensitive techniques.

PMID- 22591663
TI  - Comparison of transcutaneous contrast-enhanced ultrasound-guided injected
      hemostatic agents with traditional surgery treatment for liver, spleen and kidney
      trauma: a retrospective study.
AB  - BACKGROUND/AIMS: There is lack of studies on the effectiveness of transcutaneous
      contrast-enhanced ultrasound-guided injections of hemostatic agents for liver.
      spleen and kidney trauma. We compared treatment by hemostatic agents to surgical
      treatment in a retrospective interventional human study. METHODOLOGY: The study
      enrolled a total of 135 subjects from emergency unit of the Chinese People's
      Liberation Army General Hospital in Beijing. Within the cohort, 62 patients
      received contrast enhanced ultrasound-guided injection of hemostatic agents and
      the rest received surgical treatments. RESULTS: The injury severity score was
      lower in the hemostatic agent treatment group than surgical treatment group
      (p<0.05), but Glasgow coma scale scores did not reach statistical significance.
      The patients in the surgical treatment group had significantly higher hospital
      fees than those in the hemostatic treatment group (p<0.05), although the length
      of hospitalization did not significantly differ between two groups. Safety
      outcome variables pre- and post-treatment remained within normal limits in both
      groups. CONCLUSIONS: Hemostatic agents were more cost-effective than surgery to
      treat patients with liver, spleen and kidney trauma. However, given the limited
      sample size, subsequent studies drawing upon larger populations from multiple
      medical centers are necessary for follow-up.

PMID- 22591662
TI  - Pharmacological activation of the p53 pathway by nutlin-3 exerts anti-tumoral
      effects in medulloblastomas.
AB  - Medulloblastomas account for 20% of pediatric brain tumors. With an overall
      survival of 40%-70%, their treatment is still a challenge. The majority of
      medulloblastomas lack p53 mutations, but even in cancers retaining wild-type p53,
      the tumor surveillance function of p53 is inhibited by the oncoprotein MDM2.
      Deregulation of the MDM2/p53 balance leads to malignant transformation. Here, we
      analyzed MDM2 mRNA and protein expression in primary medulloblastomas and normal
      cerebellum and assessed the mutational status of p53 and MDM2 expression in 6
      medulloblastoma cell lines. MDM2 expression was elevated in medulloblastomas,
      compared with cerebellum. Four of 6 medulloblastoma cell lines expressed wild
      type p53 and high levels of MDM2. The tumor-promoting p53-MDM2 interaction can be
      inhibited by the small molecule, nutlin-3, restoring p53 function. Targeting the
      p53-MDM2 axis using nutlin-3 significantly reduced cell viability and induced
      either cell cycle arrest or apoptosis and expression of the p53 target gene p21
      in these 4 cell lines. In contrast, DAOY and UW-228 cells harboring TP53
      mutations were almost unaffected by nutlin-3 treatment. MDM2 knockdown in
      medulloblastoma cells by siRNA mimicked nutlin-3 treatment, whereas expression of
      dominant negative p53 abrogated nutlin-3 effects. Oral nutlin-3 treatment of mice
      with established medulloblastoma xenografts inhibited tumor growth and
      significantly increased survival. Thus, nutlin-3 reduced medulloblastoma cell
      viability in vitro and in vivo by re-activating p53 function. We suggest that
      inhibition of the MDM2-p53 interaction with nutlin-3 is a promising therapeutic
      option for medulloblastomas with functional p53 that should be further evaluated
      in clinical trials.

PMID- 22591665
TI  - Leadership and use of standards by Australian disaster medical assistance teams:
      results of a national survey of team members.
AB  - INTRODUCTION: It is likely that calls for disaster medical assistance teams
      (DMATs) will continue in response to international disasters. OBJECTIVE: As part
      of a national survey, the present study was designed to evaluate leadership
      issues and use of standards in Australian DMATs. METHODS: Data was collected via
      an anonymous mailed survey distributed via State and Territory representatives on
      the Australian Health Protection Committee, who identified team members
      associated with Australian DMAT deployments from the 2004 Asian Tsunami disaster.
      RESULTS: The response rate for this survey was estimated to be approximately 50%
      (59/118). Most of the personnel had deployed to the Asian Tsunami affected areas.
      The DMAT members were quite experienced, with 53% (31/59) of personnel in the 45
      55 years of age group. Seventy-five percent (44/59) of the respondents were male.
      Fifty-eight percent (34/59) of the survey participants had significant experience
      in international disasters, although few felt they had previous experience in
      disaster management (5%, 3/59). There was unanimous support for a clear command
      structure (100%, 59/59), with strong support for leadership training for DMAT
      commanders (85%, 50/59). However only 34% (20/59) felt that their roles were
      clearly defined pre-deployment, and 59% (35/59) felt that team members could be
      identified easily. Leadership was identified by two team members as one of the
      biggest personal hardships faced during their deployment. While no respondents
      disagreed with the need for meaningful, evidence-based standards to be developed,
      only 51% (30/59) stated that indicators of effectiveness were used for the
      deployment. CONCLUSIONS: In this study of Australian DMAT members, there was
      unanimous support for a clear command structure in future deployments, with
      clearly defined team roles and reporting structures. This should be supported by
      clear identification of team leaders to assist inter-agency coordination, and by
      leadership training for DMAT commanders. Members of Australian DMATs would also
      support the development and implementation of meaningful, evidence-based
      standards. More work is needed to identify or develop actual standards and the
      measures of effectiveness to be used, as well as the contents and nature of
      leadership training.

PMID- 22591664
TI  - Biomechanical comparison of unilateral and bilateral pedicle screws fixation for
      transforaminal lumbar interbody fusion after decompressive surgery--a finite
      element analysis.
AB  - BACKGROUND: Little is known about the biomechanical effectiveness of
      transforaminal lumbar interbody fusion (TLIF) cages in different positioning and
      various posterior implants used after decompressive surgery. The use of the
      various implants will induce the kinematic and mechanical changes in range of
      motion (ROM) and stresses at the surgical and adjacent segments. Unilateral
      pedicle screw with or without supplementary facet screw fixation in the minimally
      invasive TLIF procedure has not been ascertained to provide adequate stability
      without the need to expose on the contralateral side. This study used finite
      element (FE) models to investigate biomechanical differences in ROM and stress on
      the neighboring structures after TLIF cages insertion in conjunction with
      posterior fixation. METHODS: A validated finite-element (FE) model of L1-S1 was
      established to implant three types of cages (TLIF with a single moon-shaped cage
      in the anterior or middle portion of vertebral bodies, and TLIF with a left
      diagonally placed ogival-shaped cage) from the left L4-5 level after unilateral
      decompressive surgery. Further, the effects of unilateral versus bilateral
      pedicle screw fixation (UPSF vs. BPSF) in each TLIF cage model was compared to
      analyze parameters, including stresses and ROM on the neighboring annulus, cage
      vertebral interface and pedicle screws. RESULTS: All the TLIF cages positioned
      with BPSF showed similar ROM (<5%) at surgical and adjacent levels, except TLIF
      with an anterior cage in flexion (61% lower) and TLIF with a left diagonal cage
      in left lateral bending (33% lower) at surgical level. On the other hand, the
      TLIF cage models with left UPSF showed varying changes of ROM and annulus stress
      in extension, right lateral bending and right axial rotation at surgical level.
      In particular, the TLIF model with a diagonal cage, UPSF, and contralateral facet
      screw fixation stabilize segmental motion of the surgical level mostly in
      extension and contralaterally axial rotation. Prominent stress shielded to the
      contralateral annulus, cage-vertebral interface, and pedicle screw at surgical
      level. A supplementary facet screw fixation shared stresses around the
      neighboring tissues and revealed similar ROM and stress patterns to those models
      with BPSF. CONCLUSIONS: TLIF surgery is not favored for asymmetrical positioning
      of a diagonal cage and UPSF used in contralateral axial rotation or lateral
      bending. Supplementation of a contralateral facet screw is recommended for the
      TLIF construct.

PMID- 22591666
TI  - [Intra-uterine growth retardation: Also a concern for the internist!].

PMID- 22591667
TI  - Computational models of decision making: integration, stability, and noise.
AB  - Decision making demands the accumulation of sensory evidence over time. Questions
      remain about how this occurs, but recent years have seen progress on several
      fronts. The first concerns when optimal accumulation of evidence coincides with
      the simplest method of accumulating neural activity: summation over time. The
      second involves what computations the brain might perform when summation is
      difficult due to imprecision in neural circuits or is suboptimal due to
      uncertainty or variability in how evidence arrives. Finally, the third concerns
      sources of noise in decision circuits. Empirical studies have better constrained
      the extent of this noise, and modeling work is helping to clarify its possible
      origins.

PMID- 22591668
TI  - Meta-analysis of cytochrome P450 2C19 polymorphism and risk of adverse clinical
      outcomes among coronary artery disease patients of different ethnic groups
      treated with clopidogrel.
AB  - Loss-of-function (LOF) variants of cytochrome P450 2C19 (CYP2C19) have been
      hypothesized to be associated with lesser degrees of platelet inhibition and
      increased risk for recurrent ischemic events in patients with coronary artery
      disease on clopidogrel therapy; however, studies from Western countries have
      yielded mixed results. We aimed to assess the impact of CYP2C19 LOF variants on
      clinical outcomes from different ethnic groups. Sixteen prospective cohort
      studies including 7,035 patients carrying >= 1 CYP2C19 LOF allele and 13,750
      patients with the wild-type genotype were included in this meta-analysis.
      Carriers of >= 1 CYP2C19 LOF allele were at significantly higher risk for adverse
      clinical events compared to noncarriers during clopidogrel therapy (odds ratio
      [OR] 1.42, 95% confidence interval [CI] 1.13 to 1.78). The summary OR showed a
      significant association between CYP2C19 LOF variants and an increased risk of
      cardiac death (OR 2.18, 95% CI 1.37 to 3.47), myocardial infarction (OR 1.42, 95%
      CI 1.12 to 1.81), and stent thrombosis (OR 2.41, 95% CI 1.76 to 3.30). Stratified
      analysis by ethnicity of study population suggested higher odds of adverse
      clinical events in the Asian population with LOF variants of CYP2C19 (OR 1.89,
      95% CI 1.32 to 2.72) compared to Western populations (OR 1.28, 95% CI 1.00 to
      1.64). In conclusion, carrier status for LOF CYP2C19 is associated with an
      increased risk of adverse clinical events in patients with coronary artery
      disease on clopidogrel therapy despite differences in clinical significance
      according to ethnicity.

PMID- 22591669
TI  - Meta-analysis comparing bivalirudin versus heparin monotherapy on ischemic and
      bleeding outcomes after percutaneous coronary intervention.
AB  - With femoral access, bivalirudin decreases risks of major bleeding after
      percutaneous coronary intervention (PCI) and provides better net clinical benefit
      compared to unfractionated heparin (UFH) plus planned glycoprotein IIb/IIIa
      inhibitors. Whether this benefit exists compared to UFH monotherapy is less
      clear. We performed a systematic review and meta-analysis to compare outcomes in
      patients undergoing transfemoral PCI with UFH or bivalirudin. Randomized trials
      (n = 3) and observational studies (n = 13) comparing bivalirudin to UFH
      monotherapy were reviewed. Primary outcomes were 30-day rates of major adverse
      cardiovascular events (MACEs) including death, myocardial infarction (MI), urgent
      revascularization, as well as all-cause mortality, MI, major bleeding, and blood
      transfusion. We collected data from 16 studies involving 32,492 patients
      undergoing PCI. Most observational studies were performed in the United States,
      whereas all randomized trials were done in Europe. Compared to UFH monotherapy,
      bivalirudin was associated with similar risk of MACEs (odds ratios [OR] 0.92, 95%
      confidence interval [CI] 0.75 to 1.12), a substantial 45% relative decrease in
      major bleeding (OR 0.55, 95% CI 0.43 to 0.72), and a trend in the decrease of
      transfusion (OR 0.87, 95% CI 0.70 to 1.08). A decrease in mortality was seen in
      observational studies (OR 0.62, 95% CI 0.45 to 0.85) but remained inconclusive in
      randomized trials (OR 0.63, 95% CI 0.20 to 2.01). MI rate was similar with the 2
      anticoagulants. In conclusion, in patients undergoing transfemoral PCI, the
      benefit of bivalirudin over UFH monotherapy is driven by a significant decrease
      in major bleeding with similar rates of MACE. As PCI practice moves toward other
      bleeding-avoidance strategies such as the radial approach, future studies should
      focus on the interaction between anticoagulant strategy and access-site choice.

PMID- 22591671
TI  - Cardiac transplantation in patients with hypertrophic cardiomyopathy.
AB  - Cardiac transplantation is a treatment option for patients with hypertrophic
      cardiomyopathy (HC) who developed refractory heart failure and/or intractable
      arrhythmia. However, the pretransplant characteristics and post-transplant
      prognosis for patients with nondilated idiopathic HC has not yet fully
      elucidated. Therefore, we retrospectively reviewed 813 consecutive transplant
      recipients undergoing cardiac transplantation at Columbia University Medical
      Center from 1999 to 2010 and compared the clinical course of 41 patients with
      idiopathic HC with that of 373 patients with ischemic heart disease and 398
      patients with other heart disease. The patients with HC were younger than those
      with ischemic heart disease (47.8 +/- 14.0 vs 57.1 +/- 9.4 years; p <0.0001). The
      proportion of patients undergoing ventricular assist devise surgery for bridge-to
      transplant was lower in patients with HC than in those with ischemic heart
      disease or other heart disease (14.6% vs 31.1% vs 35.7%, all p <0.01). The post
      transplant survival of those with HC was better than that for those with ischemic
      heart disease (90.1% vs 85.8% and 83.9% vs 67.1% at 1 and 5 years, respectively;
      p = 0.0359), although it was not significantly different from those with other
      heart disease. Proportional hazards analysis revealed that the subjects with HC
      had reduced post-transplant mortality (hazard ratio 0.4760, 95% confidential
      interval 0.1889 to 0.9762; p = 0.042) on univariate, but not multivariate,
      analysis. Most patients with HC had nondilated left ventricles (left ventricular
      end-diastolic dimension <= 55 mm; n = 27), and post-transplant survival did not
      differ from that for those with dilated left ventricles (left ventricular end
      diastolic dimension >55 mm; n = 14). In conclusion, the post-transplant survival
      of those with HC did not differ from those of the subjects who underwent
      transplant for other non-HC indications.

PMID- 22591670
TI  - Predictors of atrial fibrillation termination and clinical success of catheter
      ablation of persistent atrial fibrillation.
AB  - The termination of persistent atrial fibrillation (AF) during catheter ablation
      has been associated in some, but not all, studies with reduced arrhythmia during
      clinical follow-up. We sought to determine the rate of persistent AF termination
      achievable with a stepwise ablation strategy, the predictors of AF termination,
      and the clinical outcomes associated with termination and nontermination. A total
      of 143 consecutive patients (age 62 +/- 9 years, AF duration 5.7 +/- 5.2 years)
      with persistent and longstanding persistent AF resistant to antiarrhythmic
      medication who presented in AF for catheter ablation were studied. Ablation was
      done with a stepwise approach, including pulmonary vein isolation, followed by
      complex fractionated atrial electrogram ablation and ablation of resultant atrial
      tachycardias. Clinical follow-up was then performed after a 2-month blanking
      period to assess arrhythmia recurrence, defined as AF or atrial tachycardia
      lasting >= 30 seconds. AF termination by ablation was achieved in 95 (66%) of the
      143 patients. Multivariate predictors of AF termination included longer baseline
      AF cycle length (p <0.001) and smaller left atrial size (p = 0.002). AF
      termination by ablation was associated with both a lower incidence of arrhythmia
      recurrence after a single procedure without antiarrhythmic drugs (p = 0.01) and
      overall clinical success (single or multiple procedures, with or without
      antiarrhythmic drugs; p = 0.005). On multivariate analysis, the predictors of
      overall clinical success included AF termination by ablation (p = 0.001), a
      shorter ablation duration (p = 0.002), younger age (p = 0.02), male gender (p =
      0.03), and the presence of hypertension (p = 0.03). In conclusion, among patients
      with persistent AF, termination of AF by ablation can be achieved in most
      patients and is associated with reduced recurrence of arrhythmia.

PMID- 22591672
TI  - Safety of "bridging" with eptifibatide for patients with coronary stents before
      cardiac and non-cardiac surgery.
AB  - Patients with previously implanted coronary stents are at risk for stent
      thrombosis if dual-antiplatelet therapy is prematurely discontinued. Bridging
      with a glycoprotein IIb/IIIa inhibitor has been advocated as an alternative, with
      few supporting data. The aim of this study was to determine the safety of such a
      strategy by retrospectively analyzing bleeding in 100 consecutive patients with
      previously implanted coronary stents who were bridged to surgery with
      eptifibatide after discontinuing thienopyridine therapy. A propensity-matched
      control comparison was performed for a subgroup of 71 patients who underwent
      cardiovascular surgery. Blood transfusions were required in 65% in the bridged
      group versus 66% in the control group (p = 0.86). The mean numbers of units
      transfused were 4.84 +/- 6.93 and 3.65 +/- 7.46, respectively (p >0.25). Rates of
      return to the operating room for bleeding or tamponade were 10% and 2.9%,
      respectively (p = 0.085). Increased rates of transfusion were noted for patients
      who received concomitant aspirin and/or intravenous heparin infusion. In
      conclusion, there does not appear to be any increase in the need for blood
      transfusions or rate of return to the operating room for patients being bridged
      with eptifibatide when thienopyridines are discontinued in the perioperative
      period, but concomitant use of additional antiplatelet or anticoagulant agents
      may increase transfusions and delays to surgery. Clinicians who are considering
      this strategy must weigh the risks of stent thrombosis versus bleeding.

PMID- 22591673
TI  - Outcome of noncardiac and nonvascular surgery in patients with mechanical heart
      valves.
AB  - There is a tendency to avoid noncardiac surgery in patients with mechanical heart
      valves (MHVs) owing to the increased risk of perioperative thromboembolism,
      infective endocarditis, and bleeding. We aimed to determine the risk of cardiac
      and noncardiac complications in patients with MHVs who underwent
      noncardiothoracic, nonvascular surgery. A total of 140 patients with MHVs (77
      aortic, 46 mitral, and 17 double valve) and 1,200 patients with native valves
      (control group) were prospectively followed up for a minimum of 3 months after
      noncardiothoracic and nonvascular surgery. Patients with bioprostheses were
      excluded. Those patients aged >18 years who underwent an elective, non
      outpatient, open surgical procedure were enrolled. Subcutaneous enoxaparin 1
      mg/kg, twice daily, was used as bridging anticoagulation. The demographics, co
      morbidities, and preoperative (medications, echocardiographic findings,
      laboratory results) and postoperative data were evaluated for their association
      with the occurrence of perioperative adverse events. The incidence of
      perioperative adverse cardiovascular (10.8% vs 10.7%, p = 0.985) and
      noncardiovascular (11.9% vs 11.4%, p = 0.989) events was similar in those
      patients with and without MHVs. Bleeding (18.6% vs 14.2%, p = 0.989),
      thromboembolism (3.6% vs 2%, p = 0.989), and mortality at 3 months (1.4% vs 1.3%,
      p = 0.825) were also similar for the 2 groups. In conclusion, with close follow
      up and strict adherence to the guidelines, patients with MHVs and patients with
      native heart valves undergoing noncardiac and nonvascular surgery have a similar
      risk of mortality and morbidity.

PMID- 22591674
TI  - Small molecule inhibition of 6-phosphofructo-2-kinase suppresses t cell
      activation.
AB  - BACKGROUND: T cell activation is associated with a rapid increase in
      intracellular fructose-2,6-bisphosphate (F2,6BP), an allosteric activator of the
      glycolytic enzyme, 6-phosphofructo-1-kinase. The steady state concentration of
      F2,6BP in T cells is dependent on the expression of the bifunctional 6
      phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB1-4) and the fructose
      2,6-bisphosphatase, TIGAR. Of the PFKFB family of enzymes, PFKFB3 has the highest
      kinase:bisphosphatase ratio and has been demonstrated to be required for T cell
      proliferation. A small molecule antagonist of PFKFB3, 3-(3-pyridinyl)-1-(4
      pyridinyl)-2-propen-1-one (3PO), recently has been shown to reduce F2,6BP
      synthesis, glucose uptake and proliferation in transformed cells. We hypothesized
      that the induction of PFKFB3 expression may be required for the stimulation of
      glycolysis in T cells and that exposure to the PFKFB3 antagonist, 3PO, would
      suppress T cell activation. METHODS: We examined PFKFB1-4 and TIGAR expression
      and F2,6BP concentration in purified CD3+ T cells stimulated with microbead
      conjugated agonist antibodies specific for CD3 and the co-stimulatory receptor,
      CD28. We then determined the effect of 3PO on anti-CD3/anti-CD28-induced T cell
      activation, F2,6BP synthesis, 2-[1-14C]-deoxy-d-glucose uptake, lactate
      secretion, TNF-alpha secretion and proliferation. Finally, we examined the effect
      of 3PO administration on the development of delayed type hypersensitivity to
      methylated BSA and on imiquimod-induced psoriasis in mice. RESULTS: We found that
      purified human CD3+ T cells express PFKFB2, PFKFB3, PFKFB4 and TIGAR, and that
      anti-CD3/anti-CD28 conjugated microbeads stimulated a >20-fold increase in F2,6BP
      with a coincident increase in protein expression of the PFKFB3 family member and
      a decrease in TIGAR protein expression. We then found that exposure to the PFKFB3
      small molecule antagonist, 3PO (1-10 MUM), markedly attenuated the stimulation of
      F2,6BP synthesis, 2-[1-14C]-deoxy-D-glucose uptake, lactate secretion, TNF-alpha
      secretion and T cell aggregation and proliferation. We examined the in vivo
      effect of 3PO on the development of delayed type hypersensitivity to methylated
      BSA and on imiquimod-induced psoriasis in mice and found that 3PO suppressed the
      development of both T cell-dependent models of immunity in vivo. CONCLUSIONS: Our
      data demonstrate that inhibition of the PFKFB3 kinase activity attenuates the
      activation of T cells in vitro and suppresses T cell dependent immunity in vivo
      and indicate that small molecule antagonists of PFKFB3 may prove effective as T
      cell immunosuppressive agents.

PMID- 22591675
TI  - The Development of an eHealth tool suite for prostate cancer patients and their
      partners.
AB  - BACKGROUND: eHealth resources for people facing health crises must balance the
      expert knowledge and perspective of developers and clinicians against the very
      different needs and perspectives of prospective users. This formative study
      explores the information and support needs of posttreatment prostate cancer
      patients and their partners as a way to improve an existing eHealth information
      and support system called CHESS (Comprehensive Health Enhancement Support
      System). METHODS: Focus groups with patient survivors and their partners were
      used to identify information gaps and information-seeking milestones. RESULTS:
      Both patients and partners expressed a need for assistance in decision making,
      connecting with experienced patients, and making sexual adjustments. Female
      partners of patients are more active in searching for cancer information. All
      partners have information and support needs distinct from those of the patient.
      CONCLUSIONS: Findings were used to develop a series of interactive tools and
      navigational features for the CHESS prostate cancer computer-mediated system.

PMID- 22591676
TI  - Endoscopic nasobiliary drainage and percutaneous transhepatic biliary drainage
      for the treatment of acute obstructive suppurative cholangitis: a retrospective
      study of 37 cases.
AB  - BACKGROUND/AIMS: This study compared the effectiveness and safety of endoscopic
      nasobiliary drainage(ENBD) to percutaneous transhepatic biliary drainage(PTBD)
      for the treatment of acute obstructive suppurative cholangitis (AOSC).
      METHODOLOGY: AOSC patients were assigned to undergo either ENBD (n=22) or
      PTBD(n=15). RESULTS: In the ENBD group, the procedure was successfully completed
      in 19 patients (86.4%), where- as it was converted to PTBD in 3 patients (13.6%)
      due to the failure of antegrade cholangiography. All the patients in the PTBD
      group underwent first- or second-look PTBD successfully. CONCLUSIONS: ENBD is
      effective for the treatment of AOSC, facilitating subsequent endoscopic or
      surgical intervention. PTBD is an effective and safe alternative to ENBD in
      patients unsuitable for ENBD.

PMID- 22591678
TI  - Non-anastomotic biliary strictures following orthotopic liver transplantation:
      treatment with percutaneous transhepatic biliary drainage.
AB  - BACKGROUND/AIMS: To report our experiences with percutaneous transhepatic biliary
      drainage to treat non-anastomotic biliary strictures following orthotopic liver
      transplantation in an effort to evaluate the efficacy and safety of this
      procedure. METHODOLOGY: From January 2002 to December 2011, forty-two consecutive
      patients (37 male and 5 female; aged 17-67 years, mean age 45.8 years) underwent
      percutaneous trans hepaticbiliary drainage for non-anastomotic biliary
      strictures.Twenty-six of them underwent percutaneous trans hepatic biliary
      drainage through right bile duct, 15 under-went bilateral (right bile duct and
      left bile duct) percutaneous transhepatic biliary drainage with 12 patients
      through left bile duct in the second procedure, the remaining one underwent
      percutaneous transhepatic biliary drainage through the left bile duct alone.
      RESULTS: Percutaneous transhepatic biliary drainage was successfully completed in
      all 42 patients, 23 of whom gained treatment success after first procedure. The
      other 19 patients underwent percutaneous transhepatic biliary drainage for the
      second time and 15 of them were successfully treated, the total success rate was
      90.5% (38 in 42 cases). Procedure related complications were observed in 4
      patients including cholangitis, sepsis, bleeding and acute pancreatitis.
      CONCLUSIONS: Percutaneous transhepatic biliary drainage ap-pears to be an
      effective and safe treatment with high technical success rate and few major
      complications for non-anastomotic biliary strictures following orthotopic liver
      transplantation.

PMID- 22591679
TI  - Influence of high-risk esophageal varices on outcomes in hepatocellular carcinoma
      patients: benefits of prophylactic endoscopic therapies.
AB  - BACKGROUND/AIMS: To clarify whether high-risk esophageal varices (EVs) influence
      outcomes in hepatocellular carcinoma (HCC) patients and to determine whether
      prophylactic endoscopic therapies(PETs) provide benefits for such patients.
      METHODOLOGY: Ninety-six consecutive patients with naive HCC complicated by EVs
      were analyzed. Patients with low-risk EVs (group A, n=53), those with high-risk
      EVs not treated with PETs (group B, n=31), and those with high-risk EVs treated
      with PETs (group C, n=12) were compared with respect to first bleeding and
      mortality. Furthermore, factors associated with outcomes were examined. RESULTS:
      The first bleeding rates were higher in group B than in group A; the survival
      rates were lower in group B than in group A. High-risk EVs and advanced stage HCC
      were risk factors for both outcomes in groups A and B. By contrast, the first
      bleeding rates tended to be lower in group C than in group B, while the survival
      rates did not significantly differ. In groups B and C, advanced stage HCC was a
      risk factor for both outcomes, whereas PETs significantly decreased first
      bleeding. CONCLUSIONS: High-risk EVs negatively influence both first bleeding and
      mortality in HCC patients and PETs may have a preventive effect on bleeding.

PMID- 22591680
TI  - Effect of Helicobacter pylori eradication on blood ammonia levels in cirrhotic
      patients: a systematic review.
AB  - BACKGROUND/AIMS: The effect of Helicobacter pylori (H. pylori) eradication on
      blood ammonia levels in cirrhotic patients is still controversial. We aimed to
      clarify this effect by performing a quantitative meta-analysis of published
      studies. METHODOLOGY: We searched PubMed, EMBASE and Cochrane library for studies
      which explored the effect of H. pylori eradication on blood ammonia levels in
      cirrhotic patients before March 2012. A random-effects meta-analysis was
      performed. RESULTS: Nine studies (five non-randomized control studies and four
      before-after studies) involved in 699 cirrhotic patients who were given H. pylori
      eradication eligible to our analysis. The before-after studies suggested that H.
      pylori eradication can significantly reduce the blood ammonia levels in cirrhotic
      patients (SMD=0.32, 95%CI=0.11-0.53, 12=39.6%). After included five non
      randomized control studies,the overall results suggested that H. pylori
      eradication can not reduce the blood ammonia levels in cirrhotic patients (SMD=
      0.36, 95% CI=-0.83-0.11) and with significant heterogeneity (1=89.3%). Subgroup
      analysis suggested that the no effect was found between Caucasian and Asian
      ethnicity and between cirrhotic patients with Child-Pugh class B/C <70% and >70%.
      CONCLUSIONS: The effect of eradication of H. pylori on blood ammonia levels in
      cirrhotic patients is mainly caused by the non-specific effect of antibiotics
      regardless of patients' ethnicity and impairment of liver function. However, due
      to limited studies available and low methodological quality that marked by high
      risks of bias, our study should be interpreted cautiously.

PMID- 22591681
TI  - Effect of polycarboxylate ether comb-type polymer on viscosity and interfacial
      properties of kaolinite clay suspensions.
AB  - The interactions between kaolinite clay particles and a comb-type polymer
      (polycarboxylate ether or PCE), so-called PCE super-plasticizer, were
      investigated through viscosity and surface forces measurements by a rheometer and
      a Surface Forces Apparatus (SFA). The addition of PCE shows a strong impact on
      the viscosity of concentrated kaolinite suspensions in alkaline solutions
      (pH=8.3) but a weak effect under acidic conditions (pH=3.4). In acidic solutions,
      the high viscosity measured is attributed to the strong electrostatic interaction
      between negatively charged basal planes and positively charged edge surfaces of
      clay particles. Under the alkaline condition, the suspension viscosity was found
      to first increase significantly and then decrease with increasing PCE dosages.
      The results from surface forces measurement show that PCE molecules at low
      dosages can bridge the kaolinite particles in the concentrated suspensions via
      hydrogen bonding, leading to the formation of a kaolinite-PCE "network" and hence
      an increased suspension viscosity. At high PCE dosages, clay particles are fully
      covered by PCE molecules, leading to a more dispersed kaolinite suspensions and
      hence lower suspension viscosity due to steric repulsion between the adsorbed PCE
      molecules. The insights derived from measuring viscosity and interfacial
      properties of kaolinite suspensions containing varying amount of comb-type super
      plasticizer PCE at different pH provide the foundation for many engineering
      applications and optimizing industrial processes.

PMID- 22591683
TI  - ALK-positive anaplastic large cell lymphoma with TPM3-ALK translocation.

PMID- 22591684
TI  - Src, Akt, NF-kappaB, BCL-2 and c-IAP1 may be involved in an anti-apoptotic effect
      in patients with BCR-ABL positive and BCR-ABL negative acute lymphoblastic
      leukemia.
AB  - BCR-ABL kinase has been observed to be potentially related to leukemic cell
      development. Adult patients with acute lymphoblastic leukemia (ALL) were
      evaluated to determine whether presence/absence of BCR-ABL induced differences in
      activation of Src, PI3K/Akt and NF-kappaB or in the expression of anti-apoptotic
      proteins such as BCL-2 and c-IAP1. BCR-ABL positive patients showed a
      significantly higher activation of Src and Akt compared with BCR-ABL negative
      patients and healthy donors. BCR-ABL negative patients also showed a significant
      activation of Src and low levels of Akt activation compared with healthy donors.
      Both patient groups had increased NF-kappaB activation and overexpression of BCL
      2 and c-IAP1. This is the first study to evaluate concurrently in ALL patients
      presence/absence of BCR-ABL in relation to activation of Src, Akt and NF-kappaB
      and the expression of anti-apoptotic proteins. Results suggest that these
      proteins may be involved in an anti-apoptotic signaling pathway.

PMID- 22591682
TI  - Hypoglycemic and antilipidemic properties of kombucha tea in alloxan-induced
      diabetic rats.
AB  - BACKGROUND: Diabetes has become a serious health problem and a major risk factor
      associated with troublesome health complications, such as metabolism disorders
      and liver-kidney dysfunctions. The inadequacies associated with conventional
      medicines have led to a determined search for alternative natural therapeutic
      agents. The present study aimed to investigate and compare the hypoglycemic and
      antilipidemic effects of kombucha and black tea, two natural drinks commonly
      consumed around the world, in surviving diabetic rats. METHODS: Alloxan diabetic
      rats were orally supplied with kombucha and black tea at a dose of 5 mL/kg body
      weight per day for 30 days, fasted overnight, and sacrificed on the 31st day of
      the experiment. Their bloods were collected and submitted to various biochemical
      measurements, including blood glucose, cholesterol, triglcerides, urea,
      creatinine, transaminases, transpeptidase, lipase, and amylase activities. Their
      pancreases were isolated and processed to measure lipase and alpha-amylase
      activities and to perform histological analysis. RESULTS: The findings revealed
      that, compared to black tea, kombucha tea was a better inhibitor of alpha-amylase
      and lipase activities in the plasma and pancreas and a better suppressor of
      increased blood glucose levels. Interestingly, kombucha was noted to induce a
      marked delay in the absorption of LDL-cholesterol and triglycerides and a
      significant increase in HDL-cholesterol. Histological analyses also showed that
      it exerted an ameliorative action on the pancreases and efficiently protected the
      liver-kidney functions of diabetic rats, evidenced by significant decreases in
      aspartate transaminase, alanine transaminase, and gamma-glytamyl transpeptidase
      activities in the plasma, as well as in the creatinine and urea contents.
      CONCLUSIONS: The findings revealed that kombucha tea administration induced
      attractive curative effects on diabetic rats, particularly in terms of liver
      kidney functions. Kombucha tea can, therefore, be considered as a potential
      strong candidate for future application as a functional supplement for the
      treatment and prevention of diabetes.

PMID- 22591685
TI  - Casitas B-cell lymphoma mutation in childhood T-cell acute lymphoblastic
      leukemia.
AB  - Somatic CBL mutations have been reported in a variety of myeloid neoplasms but
      are rare in acute lymphoblastic leukemia (ALL). We analyzed 77 samples from
      hematologic malignancies, identifying a somatic mutation in CBL (p.C381R) in one
      patient with T-ALL that was associated with a uniparental disomy at the CBL locus
      and a germline heterozygous mutation in one patient with JMML. Two NOTCH1
      mutations and homozygous deletions in LEF1 and CDKN2A were identified in T-ALL
      cells. The activation of the RAS pathway was enhanced, and activation of the
      NOTCH1 pathway was inhibited in NIH 3T3 cells that expressed p.C381R. This study
      appears to be the first to identify a CBL mutation in T-ALL.

PMID- 22591687
TI  - Engineering multicellular traits in synthetic microbial populations.
AB  - Without cell-to-cell communication, the organization and regulation of
      specialized cell types that underpin the development and physiology of
      multicellular organisms would be impossible. In nature, unicellular microbes have
      also been shown to display multicellular-like traits, such as intercellular
      communication, division of labor, and cooperative coordination of cellular
      activities. Likewise, the incorporation of artificial cell-to-cell communication
      into genetic circuit designs is enabling synthetic biologists to move from
      programming single cells towards the engineering of population-level behaviors
      and functions, such as diversification, spatial organization, synchronization,
      and coordinated information processing. The disciplined engineering goal of
      routinely building complex genetic circuits from well-characterized modules still
      poses challenges, owing to reusability and input-output matching problems
      resulting from information transfer being mediated through diffusible molecules.
      Optogenetic interfaces between circuits are considered as a possible solution.

PMID- 22591686
TI  - Rational design of 13C-labeling experiments for metabolic flux analysis in
      mammalian cells.
AB  - BACKGROUND: 13C-Metabolic flux analysis (13C-MFA) is a standard technique to
      probe cellular metabolism and elucidate in vivo metabolic fluxes. 13C-Tracer
      selection is an important step in conducting 13C-MFA, however, current methods
      are restricted to trial-and-error approaches, which commonly focus on an
      arbitrary subset of the tracer design space. To systematically probe the complete
      tracer design space, especially for complex systems such as mammalian cells,
      there is a pressing need for new rational approaches to identify optimal tracers.
      RESULTS: Recently, we introduced a new framework for optimal 13C-tracer design
      based on elementary metabolite units (EMU) decomposition, in which a measured
      metabolite is decomposed into a linear combination of so-called EMU basis
      vectors. In this contribution, we applied the EMU method to a realistic network
      model of mammalian metabolism with lactate as the measured metabolite. The method
      was used to select optimal tracers for two free fluxes in the system, the
      oxidative pentose phosphate pathway (oxPPP) flux and anaplerosis by pyruvate
      carboxylase (PC). Our approach was based on sensitivity analysis of EMU basis
      vector coefficients with respect to free fluxes. Through efficient grouping of
      coefficient sensitivities, simple tracer selection rules were derived for high
      resolution quantification of the fluxes in the mammalian network model. The
      approach resulted in a significant reduction of the number of possible tracers
      and the feasible tracers were evaluated using numerical simulations. Two optimal,
      novel tracers were identified that have not been previously considered for 13C
      MFA of mammalian cells, specifically [2,3,4,5,6-13C]glucose for elucidating oxPPP
      flux and [3,4-13C]glucose for elucidating PC flux. We demonstrate that 13C
      glutamine tracers perform poorly in this system in comparison to the optimal
      glucose tracers. CONCLUSIONS: In this work, we have demonstrated that optimal
      tracer design does not need to be a pure simulation-based trial-and-error
      process; rather, rational insights into tracer design can be gained through the
      application of the EMU basis vector methodology. Using this approach, rational
      labeling rules can be established a priori to guide the selection of optimal 13C
      tracers for high-resolution flux elucidation in complex metabolic network models.

PMID- 22591688
TI  - Decontamination of transvaginal ultrasound probes: review of national practice
      and need for national guidelines.
AB  - AIM: To determine the national practice of transvaginal ultrasound (TVUS) probe
      decontamination in English hospitals and to develop recommendations for guidance.
      MATERIALS AND METHODS: A literature review was undertaken to clarify best
      practice and evaluate methods of decontamination of TVUS probes. A questionnaire
      was developed to ascertain TVUS probe decontamination programmes in current use
      within English hospitals. This was sent to ultrasound leads of 100 English
      hospitals; 68 hospitals responded. RESULTS: There is a wide variation in TVUS
      probe decontamination across English hospitals. Although the majority of
      respondents (87%, 59/68) reported having clear and practical written guidelines
      for TVUS decontamination, the frequency, methods, and types of decontamination
      solutions utilized were widely variable and none meet the standards required to
      achieve high-level disinfection. CONCLUSION: While the decontamination of other
      endoluminal medical devices (e.g., flexible endoscopes) is well defined and
      regulated, the decontamination of TVUS probes has no such guidance. There appears
      to be incomplete understanding of the level of risk posed by TVUS probes, and in
      some cases, this has resulted in highly questionable practices regarding TVUS
      hygiene. There is an urgent need to develop evidence-based national guidance for
      TVUS probe decontamination.

PMID- 22591689
TI  - Percutaneous drainage as a novel approach for the treatment of Brodie's abscess.

PMID- 22591690
TI  - Mucin5B expression by lung alveolar macrophages is increased in long-term
      smokers.
AB  - This study investigated the expression of MUC5B by AMs in the lungs of cigarette
      smokers and nonsmokers. We analyzed MUC5B expression by measuring the levels of
      apomucin and mRNA in human BALF cells from 50 subjects (20 nonsmokers, 17
      patients with CB, and 13 patients with COPD). apoMUC5B was observed in BALF
      mononuclear cells in 60% of all subjects, but a significantly higher frequency of
      apoMUC5B(+) cells was found in subjects with CB (95% CI, 4.5-24.9) or COPD (95%
      CI, 6.2-39.6) than in nonsmokers (95% CI, 0.5-2.5). apoMUC5B(+) mononuclear cells
      showed strong expression of CD163, confirming their identity as AMs. MUC5B mRNA
      expression was detected by ISH in AMs of subjects investigated, and real-time
      qPCR analysis confirmed MUC5B mRNA expression. In conclusion, MUC5B is expressed
      in a subset of lung AMs and long-term cigarette smoking may increase the level of
      MUC5B produced by these cells.

PMID- 22591691
TI  - Differential expression of CD14-dependent and independent pathways for chemokine
      induction regulates neutrophil trafficking in infection.
AB  - Previous studies have shown that CD14(-/-) mice are resistant to peritoneal
      infection with some clinical isolates of Escherichia coli and that this
      resistance is accompanied by an enhanced ability to clear the bacteria; in
      contrast, normal mice expressing CD14 fail to clear the bacteria, causing severe
      sepsis and death. The enhanced clearance in CD14(-/-) mice is dependent on early
      neutrophil recruitment to the local foci of infection in the PC. The studies
      described show that neutrophil recruitment in CD14(-/-) mice occurs as a result
      of the local induction of the CXCL1 and CXCL2 chemokines, KC and MIP-2. Although
      local induction of these chemokines also occurs in normal mice, their effects on
      neutrophil recruitment to the PC appear to be counterbalanced by very high levels
      of these chemokines in the blood of normal, but not CD14(-/-), mice. Neutrophil
      recruitment to the PC is also inhibited in normal mice in response to LPS, which
      also induces high chemokine levels in the blood of normal, but not CD14(-/-),
      mice. However, MPLA, a monophosphorylated derivative of LPS, is able to induce
      early neutrophil recruitment in normal mice; this is because MPLA, unlike LPS or
      E. coli, induces MIP-2 and KC in the PC but not in the blood of normal mice. The
      pretreatment of normal mice with MPLA is able to protect them from a lethal E.
      coli infection. Thus, stimulation of a local CD14-independent chemokine induction
      pathway without triggering a systemic CD14-dependent chemokine pathway can
      protect against severe E. coli infections.

PMID- 22591693
TI  - Targeting acute myeloid leukemia cells with cytokines.
AB  - AML is a hematologic malignancy that represents 15-20% of all childhood acute
      leukemias and is responsible for more than one-half of pediatric leukemic deaths.
      The bulk tumor is continuously regenerated and sustained by rare leukemic ICs
      that proliferate slowly, thus resulting refractory to chemotherapeutic agents
      targeting highly proliferating cells within the tumor. Therefore, a complete
      eradication of the bulk tumor may depend on efficacy of therapies that target IC.
      In spite of the improvements in the treatment of AML, the difficulty to eradicate
      completely the disease incites research for innovative therapeutic approaches. In
      this regard, the role of cytokines in the treatment of AML has been investigated
      for many years, and some of them have been tested in clinical trials as a result
      of their immunomodulatory properties. Furthermore, recent preclinical studies
      highlighted the ability of the IL-12 superfamily cytokines as potent antileukemic
      agents that act directly on tumor cells and on leukemic IC, thus opening new
      perspectives for leukemic patient treatment. Here, we review the current
      knowledge about the antileukemic effects of cytokines, documented in preclinical
      and clinical studies, discussing their potential clinical application.

PMID- 22591692
TI  - CD56+ T cells inhibit HIV-1 infection of macrophages.
AB  - CD56+ T cells, the crucial component of the host innate immune system, play an
      important role in defense against viral infections. We investigated the
      noncytolytic anti-HIV-1 activity of primary CD56+ T cells. SNs collected from
      CD56+ T cell cultures inhibited HIV-1 infection and replication. This CD56+ T SN
      mediated anti-HIV-1 activity was broad-spectrum, as CD56+ T SNs could inhibit
      infections by laboratory-adapted and clinical strains of HIV-1. The antibody to
      IFN-gamma could partially block the CD56+ T SN-mediated anti-HIV effect.
      Investigation of mechanism(s) of the CD56+ T cell action on HIV-1 showed that
      although CD56+ T SN had little effect on HIV-1 entry coreceptor CCR5 expression,
      CD56+ T SN induced the expression of CC-chemokines, the ligands for CCR5. The
      antibodies to CC-chemokines also significantly blocked CD56+ T SN-mediated anti
      HIV activity. Furthermore, CD56+ T SN up-regulated the expression of STAT-1/-2
      and enhanced the expression of IRF1, -3, -7, and -9, resulting in the induction
      of endogenous IFN-alpha/beta expression in macrophages. Moreover, CD56+ T SN up
      regulated intracellular expression of APOBEC3G/3F, the recently identified HIV-1
      restriction factors. These findings provide compelling evidence that CD56+ T
      cells may have a critical role in innate immunity against HIV-1 infection.

PMID- 22591694
TI  - CCR7 ligands up-regulate IL-23 through PI3-kinase and NF-kappa B pathway in
      dendritic cells.
AB  - We reported previously that the production of IL-23 is impaired in DCs from mice
      that lack expression of the chemokines CCL19 and CCL21, which share the receptor
      CCR7, suggesting that these chemokines are required for IL-23 expression.
      However, the molecular mechanism of CCR7-mediated IL-23 production in DCs is
      unknown. We found that CCL19 and CCL21 stimulated DCs through CCR7 and induced
      transcription of IL-23p19 mRNA and IL-23 production in splenic and BMDC.
      Stimulation of DCs with CCR7 ligands induced phosphorylation of MAPK family
      members and of Akt, but only a specific PI3K inhibitor, LY294002, not inhibitors
      of ERK, JNK, or p38, decreased IL-23p19 transcription and IL-23 production. In
      DCs stimulated with CCL19 or CCL21, I kappa B alpha was degraded, and NF-kappa B
      was translocated into the nucleus. Prevention of NF-kappa B activation blocked
      chemokine-mediated IL-23p19 transcription. A PI3K inhibitor abolished NF-kappa B
      activation and IL-23 production. Based on these findings, we concluded that PI3K
      and NF-kappa B signaling pathways play a critical role in CCR7-mediated IL-23
      production in murine DCs. As IL-23 contributes to Th17 cell generation, and Th17
      cells are pathogenic in autoimmune diseases, precise elucidation of these
      mechanisms would contribute to the development of strategies to control
      autoimmune diseases.

PMID- 22591695
TI  - Enhanced elementary sulfur recovery in integrated sulfate-reducing, sulfur
      producing rector under micro-aerobic condition.
AB  - Biological treatment of sulfate-laden wastewater consists of two separate
      reactors to reduce sulfate to sulfide by sulfate-reducing bacteria (SRB) and to
      oxidize sulfide to sulfur (S(0)) by sulfide oxidation bacteria (SOB). To have
      SRB+SOB in a single reactor faced difficulty of low S(0) conversion. This study
      for the first time revealed that dissolved oxygen (DO) level can be used to
      manipulate SRB+SOB reactions in a single reactor. This work demonstrated
      successful operation of an integrated SRB+SOB reactor under micro-aerobic
      condition. At DO = 0.10-0.12 mg l(-1), since the activities of SOB were enhanced
      by limited oxygen, the removal efficiency for sulfate reached 81.5% and the
      recovery of S(0) peaked at 71.8%, higher than those reported in literature. At
      increased DO, chemical oxidation of sulfide with molecular oxygen competed with
      SOB so conversion of S(0) started to decline. At DO>0.30 mg l(-1) activities of
      SRB were inhibited, leading to failure of the SRB+SOB reactor.

PMID- 22591696
TI  - [Childhood cancer incidence in French Brittany, 1991-2005].
AB  - BACKGROUND: The aim of this study was to describe childhood cancer incidence in
      French Brittany from 1991 to 2005, as well as its temporal and geographical
      variations. METHODS: Childhood cancer incidence was analyzed from the data from
      the Brittany child tumor registry. Crude rates, world age standardized rates and
      cumulative rates were estimated for all cancers and for each diagnosis group.
      Standardized rates were also estimated for each of the four Brittany districts.
      Poisson regressions were performed to estimate trends in annual rates and to
      compare incidence rates between 2000-2005 and 1991-1999 periods, and between
      districts. RESULTS: Between 1991 and 2005, 1176 incident cancer cases were
      recorded in children younger than 15. Age standardized incidence was 169.5 cases
      per million of children per year. The most frequent cancers were leukemia (30%),
      central nervous system tumors (24%), lymphomas (12%) and neuroblastomas (8%). For
      the period 1991-2005 in Brittany, the risk of cancer diagnosis among children
      aged less than 15 years was 1/459. No significant increase trend was observed
      over the 1991-2005 period. There was however a significant or close to
      significant increase in incidence for lymphomas (RR: 1.38 [95%CI: 1.00-1.93]) and
      central nervous system tumors (RR: 1.24 [95%CI: 0.99-1.56]) between the 1991-1999
      and 2000-2005 periods. A significant decrease trend was observed for renal tumors
      over the 1991-2005 period (Estimated Annual Percent Change=-7.6%, P=0.02). There
      was no significant difference of incidence between the four districts of the
      region. CONCLUSION: For the period studied, childhood cancer incidence in French
      Brittany was lightly higher than for the whole country. Although increases in
      lymphomas and central nervous system tumors coincided with increasing use of a
      standardised data collection system for medical information, the data collected
      provided no evidence in favor of more complete data collection following
      implementation of the system.

PMID- 22591697
TI  - Immediate laparoscopic adrenalectomy versus observation: cost evaluation for
      incidental adrenal lesions with atypical imaging characteristics.
AB  - BACKGROUND: Because of controversy in the management of nonfunctional adrenal
      masses <6 cm with lipid-poor imaging characteristics, the study was conducted to
      compare the costs of observation versus immediate laparoscopic adrenalectomy.
      METHODS: A total of 370 patients who were evaluated for incidental adrenal masses
      between January 1999 and December 2007 were identified, and 32 (8.7%) patients
      had lesions with imaging characteristics that were inconsistent with a benign
      adenoma (ie, atypical appearing). Sixteen patients underwent immediate surgery
      and 16 had observation with serial imaging and biochemical studies. The
      associated total costs were subjected to intention-to-treat analysis. RESULTS: In
      the observation cohort, 7 patients converted and underwent adrenalectomy after a
      mean of 13.1 months. Initially, costs of immediate surgery exceeded those of
      observation ($12,015.72 vs $11,601.18, P = .10). After projecting costs of annual
      surveillance, a cost advantage for immediate surgery was demonstrated after 9
      years (P = .02). CONCLUSIONS: In patients with <6 cm atypical-appearing adrenal
      lesions, the costs of surgery and of observation are initially equal. After 9
      years, the costs of surveillance exceed that of initial laparoscopic
      adrenalectomy.

PMID- 22591698
TI  - Clinicopathologic characteristics of patients with non-B non-C hepatitis virus
      hepatocellular carcinoma after hepatectomy.
AB  - BACKGROUND: A substantial population of hepatocellular carcinoma (HCC) patients
      is negative for markers of hepatitis B virus and hepatitis C virus (HCV)
      infection (non-B non-C hepatitis virus [NBC]). METHODS: Clinicopathologic data
      and outcomes were compared retrospectively for HCC patients with hepatitis B
      virus, HCV, and NBC who had undergone hepatectomy. RESULTS: The TNM stage was
      significantly higher, and the prevalence of cirrhosis was significantly lower, in
      the NBC group compared with the HCV group. Among patients with a maximum tumor
      diameter of 5 cm or less, the survival rates were significantly higher in the NBC
      group than in the HCV group. Multivariate analysis revealed that preoperative
      serum des-gamma-carboxy prothrombin (DCP) level was a prognostic factor for
      survival in NBC-HCC patients. The DCP/tumor size ratio was significantly higher
      in NBC-HCC patients with normal liver histology than in patients with hepatitis
      or cirrhosis. CONCLUSIONS: NBC-HCC patients had more advanced tumors compared
      with HCV-HCC patients, but significantly higher survival rates. Measurement of
      DCP potentially is significant for early diagnosis of NBC HCC, which may increase
      the chance of curative therapy without recurrence.

PMID- 22591699
TI  - The surgery clerkship: an opportunity for preclinical credentialing in urinary
      catheterization.
AB  - BACKGROUND: At our hospital, medical students lost privileges to perform urinary
      catheterization because of concern regarding catheter-associated urinary tract
      infections. We hypothesized that trained medical students could perform urinary
      catheterization with the same proficiency as licensed practitioners. METHODS:
      Medical students completed a credentialing program in urinary catheterization.
      Prospectively, the rate of catheter-associated urinary tract infections after
      urinary catheterization performed by medical students was compared with the
      health system-wide rate of catheter-associated urinary tract infections after
      urinary catheterization performed by non-medical students using an incidence rate
      ratio (IRR). RESULTS: Over 9 months, a total of 432 and 55,401 catheter days
      accrued in patients who underwent urinary catheterization by medial students and
      non-medical students, resulting in 1 and 129 catheter-associated urinary tract
      infections, respectively. The incidence rate of catheter-associated urinary tract
      infections per 1,000 catheter days was 2.31 in the medical student-placed
      catheters and 2.33 in the non-MS-placed catheters (IRR = .99, P = .55).
      CONCLUSIONS: Preclinical credentialing in urinary catheterization resulted in the
      reinstatement of urinary catheterization privileges to qualified medical
      students. Student proficiency in urinary catheterization can match that of
      licensed practitioners.

PMID- 22591700
TI  - Facilitating safer surgery and anesthesia in a disaster zone.

PMID- 22591701
TI  - Particulate matter, DNA methylation in nitric oxide synthase, and childhood
      respiratory disease.
AB  - BACKGROUND: Air pollutants have been associated with childhood asthma and wheeze.
      Epigenetic regulation of nitric oxide synthase--the gene responsible for nitric
      oxide production--may be affected by air pollutants and contribute to the
      pathogenesis of asthma and wheeze. OBJECTIVE: Our goal was to investigate the
      association between air pollutants, DNA methylation, and respiratory outcomes in
      children. METHODS: Given residential address and buccal sample collection date,
      we estimated 7-day, 1-month, 6-month, and 1-year cumulative average PM2.5 and
      PM10 (particulate matter <= 2.5 and <= 10 um aerodynamic diameter, respectively)
      exposures for 940 participants in the Children's Health Study. Methylation of 12
      CpG sites in three NOS (nitric oxide synthase) genes was measured using a
      bisulfite-polymerase chain reaction Pyrosequencing assay. Beta regression models
      were used to estimate associations between air pollutants, percent DNA
      methylation, and respiratory outcomes. RESULTS: A 5-ug/m3 increase in PM2.5 was
      associated with a 0.20% [95% confidence interval (CI): -0.32, -0.07] to 1.0% (95%
      CI: -1.61, -0.56) lower DNA methylation at NOS2A position 1, 0.06% (95% CI: 
      0.18, 0.06) to 0.58% (95% CI: -1.13, -0.02) lower methylation at position 2, and
      0.34% (95% CI: -0.57, -0.11) to 0.89% (95% CI: -1.57, -0.21) lower methylation at
      position 3, depending on the length of exposure and CpG locus. One-year PM2.5
      exposure was associated with 0.33% (95% CI: 0.01, 0.65) higher in average DNA
      methylation of 4 loci in the NOS2A CpG island. A 5-ug/m3 increase in 7-day and 1
      year PM2.5 was associated with 0.6% (95% CI: 0.13, 0.99) and 2.8% (95% CI: 1.77,
      3.75) higher NOS3 DNA methylation. No associations were observed for NOS1. PM10
      showed similar but weaker associations with DNA methylation in these genes.
      CONCLUSIONS: PM2.5 exposure was associated with percent DNA methylation of
      several CpG loci in NOS genes, suggesting an epigenetic mechanism through which
      these pollutants may alter production of nitric oxide.

PMID- 22591702
TI  - Expression of heat shock protein 70 in nasopharyngeal carcinomas: different
      expression patterns correlate with distinct clinical prognosis.
AB  - BACKGROUND: Heat shock protein 70, a stress protein, has been implicated in tumor
      progression. However, its role in nasopharyngeal carcinoma (NPC) progression has
      not yet been clearly investigated. METHODS: Immunohistochemistry (IHC) was
      employed to examine the expression patterns of Hsp70, human leukocyte antigen -A
      (HLA-A) in NPC tissue samples. RESULTS: The expression of Hsp70 exhibited
      different spatial patterns among nuclear, membrane and cytoplasm in 507 NPC tumor
      tissues. Kaplan-Meier survival analysis demonstrated that different Hsp70
      expression patterns are correlated with different patient outcomes. High
      membranal and cytoplasmic levels of Hsp70 predicted good survival of patients. In
      contrast, high nuclear abundance of Hsp70 correlated with poor survival.
      Moreover, the membranal and cytoplasmic levels of Hsp70 were positively
      correlated with levels of the MHC I molecule HLA-A. CONCLUSIONS: Different Hsp70
      expression patterns had distinct predictive values. The different spatial
      abundance of Hsp70 may imply its important role in NPC development and provide
      insight for the development of novel therapeutic strategies involving
      immunotherapy for NPC.

PMID- 22591703
TI  - [Renal biopsies in Fabry disease: a multicenter French study].
AB  - This study has been initiated to test the scoring form developed to evaluate
      renal lesions in Fabry disease. This has been established by 10 international
      experts. Thus, we have collected data on 34 Fabry patients from 19 French centers
      ; only 28 renal biopsies were adequate for study. Males (23) and females (five)
      were of similar age (mean 50 years old). Specific glycolipid storage changes were
      found in all cases. Fibrous changes, involving glomeruli (in about 25% of the
      cases), interstitium (35% of the cases) and vascular (50 to 60%), were frequently
      detected. Renal function was significantly and negatively correlated with this
      fibrous changes, even though three patients with stages 1 and 2 chronic kidney
      disease had chronic interstitial fibrosis extending over more than 30% of the
      renal parenchyma. The extend of fibrous changes was not tightly correlated with
      age of the patients. The results of this study suggest that renal biopsy is of
      value before initiating enzyme replacement therapy, in patients older than 30 to
      40 years.

PMID- 22591704
TI  - Pitfalls, perils and payments: service user, carers and teaching staff
      perceptions of the barriers to involvement in nursing education.
AB  - BACKGROUND: There is an impetus to involve service users and carers in the
      education of nurses and a general consensus in the literature about the benefits
      that this brings to all involved. Whilst these benefits are well rehearsed in the
      literature there is little written about the potential barriers to service user
      and carer involvement in nurse education. OBJECTIVE: The objective of this study
      was to investigate service users, carers and staff views on the potential
      barriers to becoming engaged in nurse education. DESIGN: A qualitative study
      using focus group discussions (FGD) was used to canvas the views of service
      users, carers and teaching staff. SETTING: A large school of nursing in the North
      West of England. PARTICIPANTS: 38 service users and carers recruited from the
      North West of England and 23 nursing and midwifery teachers and lecturers.
      METHODS: Focus group discussions were employed as the main data collection
      method. The data were analysed using thematic analysis. RESULTS: Six themes
      occurred in the data as being negatively associated with potential and actual
      involvement: not knowing the context of the group, lack of preparation of the
      group, not being supported, not being allowed to be real, not receiving feedback,
      not being paid appropriately. CONCLUSIONS: The process of involvement is not
      without difficulties. These data show that some consideration needs to be given
      to the potential barriers to involvement if the engagement of service users and
      carers is to be effective.

PMID- 22591705
TI  - A survey of national physicians working in an active conflict zone: the
      challenges of emergency medical care in Iraq.
AB  - INTRODUCTION: There has been limited research on the perspectives and needs of
      national caregivers when confronted with large-scale societal violence. In Iraq,
      although the security situation has improved from its nadir in 2006-2007,
      intermittent bombings, and other hostilities continue. National workers remain
      the primary health resource for the affected populace. PROBLEM: To assess the
      status and challenges of national physicians working in the Emergency Departments
      of an active conflict area. METHODS: This study was a survey of civilian Iraqi
      doctors working in Emergency Departments (EDs) across Iraq, via a convenience
      sample of physicians taking the International Medical Corps (IMC) Doctor Course
      in Emergency Medicine, given in Baghdad from December 2008 through August 2009.
      RESULTS: The 148 physician respondents came from 11 provinces and over 50
      hospitals in Iraq. They described cardiovascular disease, road traffic injuries,
      and blast and bullet injuries as the main causes of death and reasons for ED
      utilization. Eighty percent reported having been assaulted by a patient or their
      family member at least once within the last year; 38% reported they were
      threatened with a gun. Doctors reported seeing a median of 7.5 patients per hour,
      with only 19% indicating that their EDs had adequate physician staffing. Only 19%
      of respondents were aware of an established triage system for their hospital, and
      only a minority had taken courses covering ACLS- (16%) or ATLS-related (24%)
      material. Respondents reported a wide diversity of prior training, with only 3%
      having some type of specialized emergency medicine degree. CONCLUSIONS: The
      results of this study describe some of the challenges faced by national health
      workers providing emergency care to a violence-stricken populace. Study findings
      demonstrate high levels of violent behavior directed toward doctors in Iraqi
      Emergency Departments, as well as staffing shortages and a lack of formal
      training in emergency medical care.

PMID- 22591706
TI  - Association of KCNJ11 E23K gene polymorphism with hypoglycemia in sulfonylurea
      treated type 2 diabetic patients.
AB  - AIMS: In addition to sulfonylurea-induced severe hypoglycemia, which however is
      not common in T2DM patients treated solely with oral hypoglycemic drugs, mild
      hypoglycemia is a frequent adverse event affecting many patients treated with
      oral hypoglycemic drugs and has a serious impact in patient adherence to therapy
      and everyday clinical practice. The aim of the present study was to investigate
      the possible association of KCNJ11 E23K polymorphism with incidence of
      sulfonylurea-induced mild hypoglycemic events. METHODS: 176 T2DM patients
      receiving sulfonylurea were included in the study, including 92 that had
      experienced drug-associated hypoglycemia and 84 that had never experienced
      hypoglycemia while on sulfonylurea treatment. KCNJ11 E23K polymorphism was
      detected by use of PCR-RFLP method. RESULTS: Frequencies of KCNJ11 E23K genotypes
      and alleles were not different between hypoglycemic and non-hypoglycemic T2DM
      patients (p=0.35 and p=0.47, respectively). In logistic regression analysis
      before and after adjustment for other factors known to affect this condition
      (age, body mass index, sulfonylurea mean daily dose, duration of T2DM, renal
      function and CYP2C9 genotype) KCNJ11 E23K polymorphism did not affect
      hypoglycemia risk. CONCLUSIONS: KCNJ11 E23K polymorphism is not associated with
      increased risk of mild hypoglycemia in sulfonylurea-treated T2DM patients.

PMID- 22591707
TI  - Genetic prediction of postpartum diabetes in women with gestational diabetes
      mellitus.
AB  - AIMS: To examine whether genetic variants that predispose individuals to type 2
      diabetes (T2D) could predict the development of diabetes after gestational
      diabetes mellitus (GDM). METHODS: 13 SNPs (FTO rs8050136, CDKAL1 rs7754840 and
      rs7756992, CDKN2A/2B rs10811661, HHEX rs1111875, IGF2BP2 rs1470579 and rs4402960,
      SLC30A8 rs13266634, TCF7L2 rs7903146, PPARG rs1801282, GCK rs1799884, HNF1A
      rs1169288, and KCNJ11 rs5219) were genotyped in 793 women with GDM after a median
      follow-up of 57 months. RESULTS: After adjustment for age and ethnicity, the
      TCF7L2 rs7903146 and the FTO rs8050136 variants significantly predicted
      postpartum diabetes; hazard ratio (95% confidence interval 1.29 (1.01-1.66) and
      1.36 (1.06-1.74), respectively (additive model) versus 1.45 (1.01-2.08) and 1.56
      (1.06-2.29) (dominant model)). Adjusting for BMI attenuated the effect of the FTO
      variant, suggesting that the effect was mediated through its effect on BMI.
      Combining all risk alleles to a weighted risk score was significantly associated
      with the risk of postpartum diabetes (hazard ratio 1.11, 95% confidence interval
      1.05-1.18, p=0.00016 after adjustment for age and ethnicity). CONCLUSIONS: The
      TCF7L2 rs7903146 and FTO rs8050136 polymorphisms, and particularly a weighted
      risk score of T2D risk alleles, predict diabetes after GDM. Further studies in
      other populations are needed to confirm our results.

PMID- 22591708
TI  - All-cause in-hospital mortality and comorbidity in diabetic and non-diabetic
      patients with stroke.
AB  - INTRODUCTION: The aim of this study was to compare diabetic and non-diabetic
      patients with stroke with regard to their all-cause in-hospital mortality and
      possible differences regarding their comorbidities. METHODS: All patients of the
      Munich Stroke Registry (2003-2004, n=537) were assessed. Hospital mortality in
      diabetic (n=160, 29.8%) and non-diabetic (n=377, 70.2%) patients was compared.
      Pre-existing comorbidities such as hypertension, coronary artery disease (CAD),
      peripheral arterial disease (PAD), albuminuria and impaired renal function (IRF)
      were noted. RESULTS: Regarding all-cause in-hospital mortality, no significant
      differences were found between diabetic and non-diabetic patients. Overall 71
      patients (13.2%) died of whom 27 (16.9%) where diabetic and 44 (11.7%) non
      diabetic patients (n.s.). Hypertension, CAD, PAD, albuminuria and IRF were more
      frequent in diabetic patients (p<0.05). CONCLUSION: Despite multiple
      comorbidities and risk factors no significant difference in all-cause in-hospital
      mortality was seen in diabetic patients as compared to non-diabetic patients.
      Improved treatment strategies and early intervention may compensate for their
      poorer prognosis.

PMID- 22591709
TI  - Baicalin, a natural compound, promotes regulatory T cell differentiation.
AB  - BACKGROUND: CD4(+)CD25(+)Foxp3(+) regulatory T (T(reg)) cells inhibit
      autoimmunity and protect against tissue injury. The development of these T(reg)
      cells is controlled by the regulator protein Foxp3, which can be enhanced by the
      in vitro activation of Foxp3 in the presence of transforming growth factor-beta.
      However, little is known about alternative methods, such as the use of natural
      products, for controlling Foxp3-mediated T(reg) cell differentiation. METHOD: HEK
      293 T cells were transfected with Foxp3 expression plasmid, and then treated with
      different compounds, Foxp3 mRNA expression was determined by real-time RT-PCR.
      CD4(+)CD25(-)T cells were stimulated with Baicalin, Foxp3 protein expression were
      analyzed by flow cytometry and confocal microscopy, the regulatory function of T
      cells stimulated with Baicalin was detected by the carboxyfluorescien
      succinimidyl ester. RESULTS: We demonstrated that Baicalin, a compound isolated
      from the Chinese herb Huangqin, induced Foxp3 protein expression in cultured T
      cells, promoted T(reg) cell differentiation and regulatory activity. Our data
      also indicated that Baicalin restored Foxp3 expression following its initial
      interleukin-6-mediated inhibition and induced Foxp3 expression in vitro.
      CONCLUSIONS: These data suggest that Baicalin may promote T(reg) cell
      differentiation and regulatory activity and may serve as a promising natural
      immunosuppressive compound for treating autoimmune inflammatory diseases.

PMID- 22591710
TI  - Acquiring ownership and the attribution of responsibility.
AB  - How is ownership established over non-owned things? We suggest that people may
      view ownership as a kind of credit given to agents responsible for making
      possession of a non-owned object possible. On this view, judgments about the
      establishment of ownership depend on attributions of responsibility. We report
      three experiments showing that people's judgments about the establishment of
      ownership are influenced by an agent's intent and control in bringing about an
      outcome, factors that also affect attributions of responsibility. These findings
      demonstrate that people do not just consider who was first to possess an object
      in judging who owns it, and are broadly consistent with the view that ownership
      is acquired through labor. The findings also suggest that rather than exclusively
      being the product of social conventions, judgments about the establishment of
      ownership over non-owned things also depend on the psychological processes
      underlying the attribution of responsibility.

PMID- 22591712
TI  - Health investment decisions in response to diabetes information in older
      Americans.
AB  - Diabetes is a very common and serious chronic disease, and one of the fastest
      growing disease burdens in the United States. Further, health behaviors, such as
      exercise, smoking, drinking, as well as weight status, are instrumental to
      diabetes management and the reduction of its medical consequences. Nine waves of
      the Health and Retirement Study are used to model the role of a recent diabetes
      diagnosis and medication on present and subsequent weight status, exercise,
      drinking and smoking activity. Several non-linear dynamic population average
      probit models are estimated. Results suggest that compared to non-diagnosed
      individuals at risk for high blood sugar, diagnosed diabetics respond initially
      in terms of increasing exercise, losing weight, and curbing smoking and drinking
      behavior, but the effect diminishes after diagnosis. Evidence of recidivism is
      also found in these outcomes, especially weight status and physical activity,
      suggesting that some behavioral responses to diabetes may be short-lived.

PMID- 22591711
TI  - Mercury, cadmium, and lead levels in human placenta: a systematic review.
AB  - BACKGROUND: Placental tissue may furnish information on the exposure of both
      mother and fetus. Mercury (Hg), cadmium (Cd), and lead (Pb) are toxicants of
      interest in pregnancy because they are associated with alterations in child
      development. OBJECTIVES: The aim of this study was to summarize the available
      information regarding total Hg, Cd, and Pb levels in human placenta and possible
      related factors. METHODS: We performed a systematic search of PubMed/MEDLINE,
      EMBASE, Lilacs, OSH, and Web of Science for original papers on total Hg, Cd, or
      Pb levels in human placenta that were published in English or Spanish (1976
      2011). Data on study design, population characteristics, collection and analysis
      of placenta specimens, and main results were extracted using a standardized form.
      RESULTS: We found a total of 79 papers (73 different studies). Hg, Cd, and Pb
      levels were reported in 24, 46, and 46 studies, respectively. Most studies
      included small convenience samples of healthy pregnant women. Studies were
      heterogeneous regarding populations selected, processing of specimens, and
      presentation of results. Hg concentrations > 50 ng/g were found in China
      (Shanghai), Japan, and the Faroe Islands. Cd levels ranged from 1.2 ng/g to 53
      ng/g and were highest in the United States, Japan, and Eastern Europe. Pb showed
      the greatest variability, with levels ranging from 1.18 ng/g in China (Shanghai)
      to 500 ng/g in a polluted area of Poland. CONCLUSION: The use of the placenta as
      a biomarker to assess heavy metals exposure is not properly developed because of
      heterogeneity among the studies. International standardized protocols are needed
      to enhance comparability and increase the usefulness of this promising tissue in
      biomonitoring studies.

PMID- 22591713
TI  - Is a QALY still a QALY at the end of life?
AB  - Recent research into end of life and palliative care has focused on the
      development of a replacement for the quality adjusted life year (QALY) as an
      outcome measure. Reasons given range from the lack of anticipated survival
      benefit from treatment to the inappropriateness of death as an anchor for valuing
      health states, or the increased value of time to the individual at the end of
      life. The Palliative Care Yardstick, has been proposed as an alternative. In this
      paper, I argue that the QALY should not be abandoned as an outcome measure in end
      of life and palliative care populations and suggest possible methods for
      generating empirical data to support or refute this. I show why the arguments
      made for replacement of the QALY are not supported by current evidence and how in
      some cases the abandonment of the QALY framework would lead to an unjustifiable
      inequitable distribution of resources.

PMID- 22591715
TI  - Literature review of disaster health research in Japan: focusing on disaster
      nursing education.
AB  - INTRODUCTION: Japan has a long history of disaster due to its location on the
      "Pacific Ring of Fire." The frequency of earthquakes experienced in recent years
      has had significant influence on disaster health research in Japan. This paper
      describes disaster health research trends in Japan, with an emphasis on disaster
      nursing research. METHOD: A systematic literature review of disaster health
      research in Japan from 2001 through 2007 was conducted for this study. The most
      commonly used database in Japan, Ichushi (version 4.0), was used for this
      literature review. The keywords and sub-keywords used were: disaster, disaster
      nursing, practice, education, ability, response, emergency, licensure,
      capability, function, prevention, planning and research. These keywords were
      sometimes used in combination to identify relevant literature. RESULTS: A total
      of 222 articles were reviewed. The number of research papers available increased
      gradually from 2001 through 2007. The most common articles used were found using
      the search category of "disaster nursing and research." Among the search
      categories, "disaster nursing and education" also had a high number of
      publications. This category also peaked in 2007. CONCLUSION: The recent
      experiences of natural disaster in Japan accelerated the impetus to explore and
      implement a disaster nursing concept into practice and nursing curricula. Further
      evidence-based studies to develop methodology and other areas of studies in
      disaster nursing, including other language databases are to be expected in the
      future.

PMID- 22591714
TI  - The CRKL gene encoding an adaptor protein is amplified, overexpressed, and a
      possible therapeutic target in gastric cancer.
AB  - BACKGROUND: Genomic DNA amplification is a genetic factor involved in cancer, and
      some oncogenes, such as ERBB2, are highly amplified in gastric cancer. We
      searched for the possible amplification of other genes in gastric cancer. METHODS
      AND RESULTS: A genome-wide single nucleotide polymorphism microarray analysis was
      performed using three cell lines of differentiated gastric cancers, and 22 genes
      (including ERBB2) in five highly amplified chromosome regions (with a copy number
      of more than 6) were identified. Particular attention was paid to the CRKL gene,
      the product of which is an adaptor protein containing Src homology 2 and 3
      (SH2/SH3) domains. An extremely high CRKL copy number was confirmed in the MKN74
      gastric cancer cell line using fluorescence in situ hybridization (FISH), and a
      high level of CRKL expression was also observed in the cells. The RNA
      interference-mediated knockdown of CRKL in MKN74 disclosed the ability of CRKL to
      upregulate gastric cell proliferation. An immunohistochemical analysis revealed
      that CRKL protein was overexpressed in 24.4% (88/360) of the primary gastric
      cancers that were analyzed. The CRKL copy number was also examined in 360 primary
      gastric cancers using a FISH analysis, and CRKL amplification was found to be
      associated with CRKL overexpression. Finally, we showed that MKN74 cells with
      CRKL amplification were responsive to the dual Src/BCR-ABL kinase inhibitor
      BMS354825, likely via the inhibition of CRKL phosphorylation, and that the
      proliferation of MKN74 cells was suppressed by treatment with a CRKL-targeting
      peptide. CONCLUSION: These results suggested that CRKL protein is overexpressed
      in a subset of gastric cancers and is associated with CRKL amplification in
      gastric cancer. Furthermore, our results suggested that CRKL protein has the
      ability to regulate gastric cell proliferation and has the potential to serve as
      a molecular therapy target for gastric cancer.

PMID- 22591716
TI  - Ki-67 expression predicts radiosensitivity in oral squamous cell carcinoma.
AB  - The prognostic relevance of Ki-67 expression in oral squamous cell carcinoma
      (OSCC) is still controversial. As proliferating cells are more susceptible to
      ionizing radiation, the authors investigated if a high proliferation rate
      reflected by Ki-67 expression, predicts radiosensitivity in OSCC patients. In 52
      patients with OSCC who received primary surgery followed by radiation therapy,
      the proliferation rate was assessed by Ki-67 immunhistochemistry and correlated
      to recurrent free survival and overall survival. Low proliferative carcinomas
      showed a significantly shorter mean time to recurrence of 27.5 months compared to
      49.5 months of high proliferative tumours (p=0.048). The 5-year survival rate of
      low proliferative tumours was 49% compared to 80% for high proliferative tumours
      (p=0.042). This study indicates that tumours with high proliferative activity are
      more susceptible to radiation therapy. Ki-67 might be used as a marker to predict
      the response to radiation therapy in patients with OSCC.

PMID- 22591717
TI  - A comparative study of the effect of suture-less and multiple suture techniques
      on inflammatory complications following third molar surgery.
AB  - The aim of this prospective randomized study was to evaluate the effect of not
      using sutures on postoperative pain, swelling and trismus after lower third molar
      surgery. 80 patients with impacted lower third molars were referred for surgical
      extraction (42 males; 38 females; aged 18-38 years). The patients were randomly
      divided into two equal groups (sutures n=40; suture-less n=40). In the
      experimental group, the flaps were replaced without suturing. The control group
      was selected using the same criteria and treated under the same surgical protocol
      as the experimental group, except that the flaps were apposed using multiple
      sutures. Pain, swelling and trismus were evaluated at 24 h, 48 h and 1 week
      postoperatively in both groups. The operation time was found to be significantly
      longer in the multiple sutures group (p<0.05). There was significantly less pain,
      swelling and trismus at 24 h and 48 h, respectively, in the suture-less group
      (p<0.05). There was no significant difference between the two treatment groups in
      terms of pain, swelling and trismus, at 1 week postoperatively (p>0.05). There is
      less postoperative pain, swelling and trismus with the suture-less technique in
      third molar surgery.

PMID- 22591718
TI  - RASSF1C modulates the expression of a stem cell renewal gene, PIWIL1.
AB  - BACKGROUND: RASSF1A and RASSF1C are two major isoforms encoded by the Ras
      association domain family 1 (RASSF1) gene through alternative promoter selection
      and mRNA splicing. RASSF1A is a well established tumor suppressor gene. Unlike
      RASSF1A, RASSF1C appears to have growth promoting actions in lung cancer. In this
      article, we report on the identification of novel RASSF1C target genes in non
      small cell lung cancer (NSCLC). METHODS: Over-expression and siRNA techniques
      were used to alter RASSF1C expression in human lung cancer cells, and Affymetrix
      microarray study was conducted using NCI-H1299 cells over-expressing RASSF1C to
      identify RASSF1C target genes. RESULTS: The microarray study intriguingly shows
      that RASSF1C modulates the expression of a number of genes that are involved in
      cancer development, cell growth and proliferation, cell death, and cell cycle. We
      have validated the expression of some target genes using qRT-PCR. We demonstrate
      that RASSF1C over-expression increases, and silencing of RASSF1C decreases, the
      expression of PIWIL1 gene in NSCLC cells using qRT-PCR, immunostaining, and
      Western blot analysis. We also show that RASSF1C over-expression induces
      phosphorylation of ERK1/2 in lung cancer cells, and inhibition of the MEK-ERK1/2
      pathway suppresses the expression of PIWIL1 gene expression, suggesting that
      RASSF1C may exert its activities on some target genes such as PIWIL1 through the
      activation of the MEK-ERK1/2 pathway. Also, PIWIL1 expression is elevated in lung
      cancer cell lines compared to normal lung epithelial cells. CONCLUSIONS: Taken
      together, our findings provide significant data to propose a model for
      investigating the role of RASSF1C/PIWIL1 proteins in initiation and progression
      of lung cancer.

PMID- 22591719
TI  - Correlation between dynamic contrast-enhanced perfusion MRI relative cerebral
      blood volume and vascular endothelial growth factor expression in meningiomas.
AB  - PURPOSE: To determine whether there is a correlation between vascular endothelial
      growth factor (VEGF) expression and cerebral blood flow (CBV) measurements in
      dynamic contrast-enhanced susceptibility perfusion magnetic resonance imaging
      (MRI) and to correlate the perfusion characteristics in high- versus low-grade
      meningiomas. METHODS AND MATERIALS: A total of 48 (24 high-grade and 24 low
      grade) meningiomas with available dynamic susceptibility-weighted MRI were
      retrospectively reviewed for maximum CBV and semiquantitative VEGF
      immunoreactivity. Correlation between normalized CBV and VEGF was made using the
      Spearman rank test and comparison between CBV in high- versus low-grade
      meningiomas was made using the Wilcoxon test. RESULTS: There was a significant (P
      = .01) correlation between normalized maximum CBV and VEGF scores with a Spearman
      correlation coefficient of 0.37. In addition, there was a significant (P < .01)
      difference in normalized maximum CBV ratios between high-grade meningiomas (mean
      12.6; standard deviation 5.2) and low-grade meningiomas (mean 8.2; standard
      deviation 5.2). CONCLUSION: The data suggest that CBV accurately reflects VEGF
      expression and tumor grade in meningiomas. Perfusion-weighted MRI can potentially
      serve as a useful biomarker for meningiomas, pending prospective studies.

PMID- 22591720
TI  - Semi-automatic segmentation software for quantitative clinical brain glioblastoma
      evaluation.
AB  - RATIONALE AND OBJECTIVES: Quantitative measurement provides essential information
      about disease progression and treatment response in patients with glioblastoma
      multiforme (GBM). The goal of this article is to present and validate a software
      pipeline for semi-automatic GBM segmentation, called AFINITI (Assisted Follow-up
      in NeuroImaging of Therapeutic Intervention), using clinical data from GBM
      patients. MATERIALS AND METHODS: Our software adopts the current state-of-the-art
      tumor segmentation algorithms and combines them into one clinically usable
      pipeline. Both the advantages of the traditional voxel-based and the deformable
      shape-based segmentation are embedded into the software pipeline. The former
      provides an automatic tumor segmentation scheme based on T1- and T2-weighted
      magnetic resonance (MR) brain data, and the latter refines the segmentation
      results with minimal manual input. RESULTS: Twenty-six clinical MR brain images
      of GBM patients were processed and compared with manual results. The results can
      be visualized using the embedded graphic user interface. CONCLUSION: Validation
      results using clinical GBM data showed high correlation between the AFINITI
      results and manual annotation. Compared to the voxel-wise segmentation, AFINITI
      yielded more accurate results in segmenting the enhanced GBM from multimodality
      MR imaging data. The proposed pipeline could be used as additional information to
      interpret MR brain images in neuroradiology.

PMID- 22591721
TI  - Engineering and radiology: implications for education.

PMID- 22591722
TI  - Radiofrequency ablation of the liver: effect of variation of portal venous blood
      flow on lesion size in an in-vitro perfused bovine liver.
AB  - RATIONALE AND OBJECTIVES: An in vitro perfused bovine liver model was used to
      evaluate the relationship between the sizes of radiofrequency ablation lesions
      and variation in portal venous blood flow. MATERIALS AND METHODS: Fourteen bovine
      livers were perfused with autologous heparinized blood at 37 degrees C and 40% to
      50% oxygenation via the portal vein. Flow rates were adjusted from 10 to 50
      mL/min/100 g tissue. A 480-kHz generator and a 3.0-cm monopolar internally cooled
      electrode were used to create 57 ablations. The long-axis diameter, short-axis
      diameter (SAD), and volume of each ablation zone were measured and calculated
      from the dissected livers. Correlations between SAD, long-axis diameter, and
      volume versus blood flow were assessed using linear regression analysis. RESULTS:
      SAD and lesion volume demonstrated inverse linear correlations with blood flow
      (for SAD, y = -0.044x + 3.925, r = 0.836, P < .001; for volume, y = -0.556x +
      31.574, r = 0.842, P < .001). A 10 mL/min/100 g change in flow rate produced an
      average 4.4 +/- 0.4 mm change in SAD and an average 5.6 +/- 0.5 cm(3) change in
      volume. Long-axis diameter was not correlated with blood flow (y = -0.7694x +
      4.1899, r = 0.2173, P = .111). CONCLUSIONS: The SAD and volume of radiofrequency
      ablation lesions have statistically significant inverse linear correlations with
      portal venous blood flow, with an average 4.4-mm change in SAD and an average 5.6
      cm(3) change in volume for each 10 mL/min/100 g change in flow rate.

PMID- 22591723
TI  - Radiofrequency ablation of retroperitoneal metastatic lymph nodes from
      hepatocellular carcinoma.
AB  - RATIONALE AND OBJECTIVES: To retrospectively evaluate effectiveness and safety of
      radiofrequency (RF) ablation with retroperitoneal metastatic lymph nodes from
      hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Thirty-two patients with
      retroperitoneal metastatic lymph node recurrence from HCC were enrolled in our
      study and the patients stratified into two groups based on the treatment.
      Nineteen patients in Group A were percutaneously treated and each metastatic
      lymph node was ablated with computed tomographic (CT) guidance. Thirteen patients
      in Group B only underwent RF ablation for hematogenous metastases, but did not
      undergo RF ablation or any other treatment for metastatic lymph nodes. Follow-up
      contrast material-enhanced CT or positron emission tomographic scans were
      reviewed and Kaplan-Meier survival estimates were analyzed. RESULTS: There were
      no significant differences between characteristics of the two groups. Kaplan
      Meier analysis indicated the patients of Group A had an overall survival of 26.3%
      at 1 year compared with 7.7% for those of Group B. Mantel-Cox log rank test
      showed the 1-year survival rate of Group A was significantly higher than that of
      Group B (P = .029). In Group A, the local control rate of 3, 6, 10, and 15 months
      was 78.9%, 73.3%, 41.7%, and 25.0%, respectively. Sixteen, 12, 6, and 2 patients
      showed no evidence of local progression for 3, 6, 10, and 15 months,
      respectively. There was no thermal injury of gastrointestinal tract or bile duct
      during RF ablation in all the 19 patients of Group A. CONCLUSION: RF ablation is
      effective and may be safely applied to retroperitoneal metastatic lymph nodes
      from HCC.

PMID- 22591724
TI  - Hyperpolarized 129Xe magnetic resonance imaging: tolerability in healthy
      volunteers and subjects with pulmonary disease.
AB  - RATIONALE AND OBJECTIVES: The objective of this study was to evaluate the
      tolerability of hyperpolarized (129)Xe gas inhaled from functional residual
      capacity and magnetic resonance imaging in healthy subjects and those with
      pulmonary disease. MATERIALS AND METHODS: Twelve healthy volunteers (mean age, 59
      +/- 17 years), seven subjects with asthma (mean age, 47 +/- 7 years), 10 subjects
      with chronic obstructive pulmonary disease (mean age, 74 +/- 4 years), three
      subjects with cystic fibrosis (mean age, 27 +/- 10 years), and a single subject
      with radiation-induced lung injury (age, 66 years) were enrolled and evaluated
      over 43 visits with 136 anoxic inhalations of 500 mL (129)Xe gas mixed with 500
      mL (4)He gas. Oxygen saturation and heart rate were monitored during the breath
      hold and imaging; subjects were queried for adverse events (AEs) before and
      immediately following gas inhalation and for 24 hours after the last dose.
      RESULTS: No subjects withdrew from the study or reported serious, hypoxic, or
      severe AEs. Over the course of 136 dose administrations, two mild AEs (1%) were
      reported in two different subjects (two of 33 [6%]). One of these AEs (light
      headedness) was temporally related and judged as possibly related to (129)Xe
      administration and resolved without treatment within 2 minutes. Statistically
      significant but clinically insignificant changes in oxygen saturation and heart
      rate were observed after inhalation (P < .001), and both resolved 1 minute later,
      with no difference between subject groups. CONCLUSIONS: Inhalation of
      hyperpolarized (129)Xe gas and subsequent magnetic resonance imaging were well
      tolerated in healthy subjects and ambulatory subjects with obstructive and
      restrictive pulmonary disease.

PMID- 22591725
TI  - Behavioral alteration and DNA damage of freshwater snail Bellamya aeruginosa
      stressed by ethylbenzene and its tissue residue.
AB  - To study the sublethal effects induced by ethylbenzene and the capability of a
      freshwater gastropod Bellamya aeruginosa to take up and depurate ethylbenzene,
      the snail was subjected to two treatments, a 23-day exposure period followed by a
      17-day depuration period. Behavioral alteration, namely retraction response, was
      observed during the exposure period, and the proportion of retracted snails
      increased under each treatment as the exposure time prolonged but there was no
      linear relationship between the retracted proportion and the exposure dose. Such
      behavioral alteration was probably due to the disturbance of membrane
      permeability stressed by ethylbenzene. Ethylbenzene uptake in unretracted snails
      was greater than in retracted snails, while the depuration abilities in the two
      different responses of snails had no significant difference from each other.
      Because of the limited capability of snails to detoxify ethylbenzene, the
      depuration was mainly through a slow excretion process and therefore ethylbenzene
      was still present in the tissue of snail after 17-day depuration. DNA damage was
      induced significantly in snails exposed to ethylbenzene, and the levels of DNA
      damage showed positive time-response and dose-response relationships, and
      moreover the levels of DNA damage had no difference between the two different
      responses of snails. There was no linear relationship between the level of DNA
      damage and the amount of residual ethylbenzene in tissue, which may be related to
      the adaptation mechanism in snail. Overall, the results suggest that the snail
      has high capability to take up ethylbenzene and low ability to depurate it, and
      ethylbenzene has potential genotoxicity to snail.

PMID- 22591726
TI  - A randomized trial of induction chemotherapy plus concurrent chemoradiotherapy
      versus induction chemotherapy plus radiotherapy for locoregionally advanced
      nasopharyngeal carcinoma.
AB  - The aim of this randomized study was to compare the efficacy of induction
      chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) versus induction
      chemotherapy plus radiotherapy (IC+RT) for patients with locoregionally advanced
      nasopharyngeal carcinoma. From August 2002 to April 2005, 408 patients were
      randomly divided into two groups: an IC+CCRT group and an IC+RT group. Patients
      in both groups received the same induction chemotherapy: two cycles of
      floxuridine (FuDR)+carboplatin (FuDR, 750 mg/m(2), d1-5; carboplatin, area under
      the curve [AUC]=6). The patients received radiotherapy 1 week after they finished
      the induction chemotherapy. The patients in the IC+CCRT group also received
      carboplatin (AUC=6) on days 7, 28, and 49 of radiotherapy. Eight patients did not
      meet the inclusion criteria, and the remaining 400 cases were analyzed. Grade III
      or IV toxicity was found in 28.4% of the patients in the IC+CCRT group and 13.1%
      of those in the IC+RT group (P<.001). Five-year overall survival rates were 70.3%
      and 71.7% (P=0.734) in the IC+CCRT and IC+RT groups, respectively. No significant
      differences in failure-free survival, locoregional control, and distant control
      were found between the two groups. Compared with the IC+RT program, the IC+CCRT
      program used in the present study did not improve the overall survival and
      failure-free survival in patients with locoregionally advanced nasopharyngeal
      carcinoma. Using carboplatin in the concurrent chemoradiotherapy was not suitable
      for nasopharyngeal carcinoma.

PMID- 22591727
TI  - [Chagas disease (American trypanosomiasis) in France].
AB  - Chagas disease is an anthropozoonotic infection caused by Trypanosoma cruzi,
      transmitted by a hematophagous triatomine insect vector belonging to the
      Reduviidae family, while taking a blood meal. There is a large reservoir of wild
      and domestic mammals. Human contamination may come via vectorial, transplacental,
      and digestive routes, blood transfusion, organ or tissue transplantation, and by
      accident. The disease has two phases. The acute phase, oligosymptomatic, is
      frequently undiagnosed. It is followed by a chronic phase. Most of the infected
      patients remain asymptomatic all life-long. But 10 or 25 years later, one third
      of infected patients present with cardiac or digestive complications. Chagas
      disease is endemic in Latin America, from Mexico to Argentina. In French Guyana,
      the prevalence of the infection was estimated at 0.25% and 0.5% (from 500 to 1000
      infected patients) on blood samples collected from 1992 to 1998. In 2000 and
      2009, 192 cases were diagnosed. In this district, there is no established
      domestic vector and the transmission risk is low. The vector is very easily found
      in forest habitats and even in the peridomestic persistent forest, with an
      infection rate of 46 to 86%. Vectorial eradication is impossible. Fighting
      against Chagas disease in French Guyana relies more on individual protection,
      control of blood transfusion, prevention of mother-to-child transmission,
      diagnosis, and treatment of infected patients than on vectorial control.

PMID- 22591729
TI  - Problems and issues in implementing innovative curriculum in the developing
      countries: the Pakistani experience.
AB  - BACKGROUND: The Government of Pakistan identified 4 medical Colleges for
      introduction of COME, one from each province. Curriculum was prepared by the
      faculty of these colleges and launched in 2001 and despite concerted efforts
      could not be implemented. The purpose of this research was to identify the
      reasons for delay in implementation of the COME curriculum and to assess the
      understanding of the stakeholders about COME. METHODS: Mixed methods study design
      was used for data collection. In-depth interviews, mail-in survey questionnaire,
      and focus group discussions were held with the representatives of federal and
      provincial governments, Principals of medical colleges, faculty and students of
      the designated colleges. Rigor was ensured through independent coding and
      triangulation of data. RESULTS: The reasons for delay in implementation differed
      amongst the policy makers and faculty and included thematic issues at the
      institutional, programmatic and curricular level. Majority (92% of the faculty)
      felt that COME curriculum couldn't be implemented without adequate
      infrastructure. The administrators were willing to provide financial assistance,
      political support and better coordination and felt that COME could improve the
      overall health system of the country whereas the faculty did not agree to it.
      CONCLUSION: The paper discusses the reasons of delay based on findings and
      identifies the strategies for curriculum change in established institutions. The
      key issues identified in our study included frequent transfer of faculty of the
      designated colleges and perceived lack of: Continuation at the policy making
      level. Communication between the stakeholders. Effective leadership.

PMID- 22591730
TI  - Thieno[3,2-d]pyrimidin-4(3H)-one derivatives as PDK1 inhibitors discovered by
      fragment-based screening.
AB  - Ligand efficient fragments binding to PDK1 were identified by an NMR fragment
      based screening approach. Computational modeling of the fragments bound to the
      active site led to the design and synthesis of a series of novel 6,7
      disubstituted thienopyrimidin-4-one compounds, with low micromolar inhibitory
      activity against PDK1 in a biochemical enzyme assay.

PMID- 22591731
TI  - Subtypes in bulimia nervosa: the role of eating disorder symptomatology, negative
      affect, and interpersonal functioning.
AB  - BACKGROUND: The aim of the study was to investigate whether patients with bulimia
      nervosa (BN) could be subdivided into clinically meaningful groups reflecting the
      complex patterns of eating disorder symptoms and personality characteristics that
      face the clinician. METHODS: Seventy patients diagnosed with BN using the Eating
      Disorder Examination were assessed with measures of negative affect, attachment
      patterns, and interpersonal problems. An exploratory hierarchical cluster
      analysis was performed. RESULTS: The study found two main subtypes differing
      primarily in terms of symptom severity and level of negative affect, but these
      subtypes were further subdivided into four clinically relevant subtypes: A
      dietary restraint/negative affect/high symptomatic group, an emotionally
      overcontrolled group, a low dietary restraint/emotionally underregulated group,
      and a high functioning/securely attached group. CONCLUSIONS: The study indicates
      that cluster-analytic studies, including a broad range of instruments measuring
      eating disorder symptoms as well as negative affect, relational patterns, and
      other personality characteristics, may contribute to an integration of previously
      suggested models of subtypes in BN.

PMID- 22591732
TI  - Stroke etiology determines effectiveness of retrievable stents.

PMID- 22591733
TI  - Flow control techniques for Onyx embolization of intracranial dural arteriovenous
      fistulae.
AB  - OBJECTIVES: Experience of flow control techniques during endovascular treatment
      of intracranial dural arteriovenous fistulas (DAVFs) using the Onyx liquid
      embolic system is reported, with an emphasis on high flow shunts. METHODS: Data
      were evaluated in patients with DAVFs treated endovascularly with Onyx.
      Adjunctive techniques with coils, acrylics and balloon assistance were utilized
      to reduce the rate of flow with transarterial and transvenous approaches.
      RESULTS: The following types of adjunctive techniques were used in 58 patients
      who underwent a total of 84 embolization sessions with Onyx: transvenous coiling
      with transvenous or transarterial Onyx embolization in 36 patients, transarterial
      coiling with transarterial Onyx embolization in eight patients, arterial or
      venous balloon assisted technique with transarterial or transvenous Onyx
      embolization in 11 patients, transarterial high concentration acrylics with
      transarterial Onyx embolization in one patient and staged transarterial or
      transvenous coiling and Onyx embolization in two patients. Complete obliteration
      of the fistulae was achieved in 41 patients (70.7%) and 27 patients (65.9%) with
      high flow fistulae after endovascular treatment alone. Periprocedural
      complications were encountered in 16 patients, and 13 complications were
      associated with the adjunctive techniques. There were four neurologic and two non
      neurologic clinical sequelae. Distal Onyx migration occurred in four,
      microcatheter retention in three and cranial neuropathy in three patients. There
      was one instance each of cerebellar hemorrhage, thromboembolism, coil stretching
      and retention, and dissection. 56 survivors experienced complete resolution or
      significant improvement of their symptoms on follow-up. CONCLUSIONS: Flow control
      techniques are safe and effective adjunctive methods in primary endovascular Onyx
      embolization of high flow DAVFs.

PMID- 22591734
TI  - Quantitative mRNA expression of genes involved in angiogenesis, coagulation and
      inflammation in multiforme glioblastoma tumoral tissue versus peritumoral brain
      tissue: lack of correlation with clinical data.
AB  - Glioblastoma multiforme is a very aggressive brain tumor. Angiogenesis, the
      formation of new blood vessels from pre-existing ones, is a process that plays an
      essential role in cancer development. The evolution of this process depends upon
      several proangiogenic factors as well as inhibitors of angiogenesis. Coagulation
      and inflammation also play an important role in tumorigenesis. Their expression
      is controlled by over- or under-expression of certain genes. The objective of our
      study was to evaluate the expression, in tissue samples, of a set of six genes
      involved in tumoral angiogenesis. The study concerned a group of 14 patients with
      pathologically-confirmed glioblastoma multiforme. Samples of tumoral and
      peritumoral brain tissue were taken during surgery. We used RT-PCR to evaluate
      the expression of six genes involved in angiogenesis: VEGF, PDGF, EPCR, TNF, ICAM
      1 and CTGF. Gene expression was calculated by comparing the values obtained for
      the tumoral tissue with those obtained for the peritumoral tissue. Increased
      transcription of VEGF, PDGF and ICAM-1 genes were observed in glioblastoma
      tumoral tissues compared with peritumoral brain tissues. Correlations were
      observed between transcription of the CTGF and TNF genes (rho = 0.54, p-value =
      0.05) and PDGF and ICAM-1 genes (rho = 0.54, p-value = 0.05). Under-expression of
      CTGF, EPCR and TNF genes was observed in glioblastoma tumoral tissue in
      comparison with peritumoral brain tissue. The association between gene expression
      and histopathological results (endothelial hyperplasia, coagulation necrosis and
      ischemic necrosis) was evaluated. No statistically significant associations were
      observed between gene expression and survival rates.

PMID- 22591735
TI  - Hypertrophic cardiomyopathy in children.
AB  - Hypertrophic cardiomyopathy (HCM) is the second commonest form of heart muscle
      disease affecting children and adolescents and is a leading cause of sudden death
      in young athletes. The aetiology of HCM is heterogeneous in the paediatric
      population, and includes inborn errors of metabolism, neuromuscular disorders and
      malformation syndromes. However, most cases of apparently idiopathic HCM in
      childhood are caused by mutations in cardiac sarcomere protein genes. Patients
      with metabolic or syndromic HCM usually present in infancy or early childhood,
      whereas those with neuromuscular disorders are more frequently diagnosed in
      adolescence. The diagnosis of HCM in infants is often made during evaluation for
      a heart murmur or congestive heart failure. Older children are usually referred
      for evaluation of symptoms, electrocardiographic abnormalities or heart murmur,
      or for family screening following the diagnosis of HCM in a relative. Risk
      stratification in the paediatric population remains a challenge. As most cases of
      HCM are familial, evaluation of first-degree relatives and other family members
      at risk of inheriting the disease should be a routine component of clinical
      management.

PMID- 22591736
TI  - Cilostazol in NICE guideline.

PMID- 22591737
TI  - Heart failure and dysrhythmias after maternal placental syndromes: HAD MPS Study.
AB  - BACKGROUND: Maternal placental syndromes (MPS)-gestational hypertension, pre
      eclampsia and placental abruption/infarction-are more prevalent in women with
      features of the metabolic syndrome (MetSyn). Both MPS and the MetSyn predispose
      to left ventricular impairment and sympathetic dominance after delivery. Whether
      this translates into a higher risk of heart failure (HF) and cardiac dysrhythmias
      is not known. OBJECTIVE: To determine the risk of new onset of HF and
      dysrhythmias among women after a prior MPS-affected pregnancy. METHODS: A
      retrospective cohort study was carried out of 1,130,764 individual women with a
      delivery in Ontario between 1992 and 2009, excluding those with cardiac or
      thyroid disease 1 year before delivery. The risk of a composite outcome of a
      hospitalisation for HF or an atrial or ventricular dysrhythmia was compared in
      women with and without MPS, starting 1 year after delivery. RESULTS: 75,242
      individuals (6.7%) experienced a MPS. After a median duration of 7.8 years, the
      composite outcome occurred in 148 women with MPS (2.54 per 10,000 person-years)
      and 1062 women without MPS (1.28 per 10,000 person-years) (crude HR=2.00, 95% CI
      1.68 to 2.38). The mean age at composite outcome was 37.8 years. The HR was 1.61
      (95% CI 1.35 to 1.91) after adjustment for demographic characteristics, diabetes,
      obesity, dyslipidaemia and drug dependence or tobacco use, as well as coronary
      artery disease or thyroid disease >1 year after delivery. The adjusted HRs were
      minimally reduced by further adjusting for chronic hypertension (1.51, 95% CI
      1.26 to 1.80) and were higher in women with MPS plus preterm delivery and poor
      fetal growth (2.42, 95% CI 1.25 to 4.67). CONCLUSIONS: Women with MPS are at
      higher risk of premature HF and dysrhythmias, especially when perinatal morbidity
      is present.

PMID- 22591738
TI  - Cardiovascular registries: a novel platform for randomised clinical trials.

PMID- 22591739
TI  - Surgical care during humanitarian crises: a systematic review of published
      surgical caseload data from foreign medical teams.
AB  - OBJECTIVE: Humanitarian surgery is often organized and delivered with short
      notice and limited time for developing unique strategies for providing care.
      While some surgical pathologies can be anticipated by the nature of the crisis,
      the role of foreign medical teams in treating the existing and unmet burden of
      surgical disease during crises is unclear. The purpose of this study was to
      examine published data from crises during the years 1990 through 2011 to
      understand the role of foreign medical teams in providing surgical care in these
      settings. METHODS: A literature search was completed using PubMed, MEDLINE, and
      EMBASE databases to locate relevant manuscripts published in peer-reviewed
      journals. A qualitative review of the surgical activities reported in the studies
      was performed. RESULTS: Of 185 papers where humanitarian surgical care was
      provided by a foreign medical team, only 11 articles met inclusion criteria. The
      reporting of surgical activities varied significantly, and pooled statistical
      analysis was not possible. The quality of reporting was notably poor, and
      produced neither reliable estimates of the pattern of surgical consultations nor
      data on the epidemiology of the burden of surgical diseases. The qualitative
      trend analysis revealed that the most frequent procedures were related to soft
      tissue or orthopedic surgery. Procedures such as caesarean sections, hernia
      repairs, and appendectomies also were common. As length of deployment increased,
      the surgical caseload became more reflective of the existing, unmet burden of
      surgical disease. CONCLUSIONS: This review suggests that where foreign medical
      teams are indicated and requested, multidisciplinary surgical teams capable of
      providing a range of emergency and essential surgical, and rehabilitation
      services are required. Standardization of data collection and reporting tools for
      surgical care are needed to improve the reporting of surgical epidemiology in
      crisis-affected populations.

PMID- 22591740
TI  - Relative contribution of DNAPL dissolution and matrix diffusion to the long-term
      persistence of chlorinated solvent source zones.
AB  - The relative contribution of dense non-aqueous phase liquid (DNAPL) dissolution
      versus matrix diffusion processes to the longevity of chlorinated source zones
      was investigated. Matrix diffusion is being increasingly recognized as an
      important non-DNAPL component of source behavior over time, and understanding the
      persistence of contaminants that have diffused into lower permeability units can
      impact remedial decision-making. In this study, a hypothetical DNAPL source zone
      architecture consisting of several different sized pools and fingers originally
      developed by Anderson et al. (1992) was adapted to include defined low
      permeability layers. A coupled dissolution-diffusion model was developed to allow
      diffusion into these layers while in contact with DNAPL, followed by diffusion
      out of these same layers after complete DNAPL dissolution. This exercise was
      performed for releases of equivalent masses (675 kg) of three different
      compounds, including chlorinated solvents with solubilities ranging from low
      (tetrachloroethene (PCE)), moderate (trichloroethene (TCE)) to high
      (dichloromethane (DCM)). The results of this simple modeling exercise demonstrate
      that matrix diffusion can be a critical component of source zone longevity and
      may represent a longer-term contributor to source longevity (i.e., longer time
      maintaining concentrations above MCLs) than DNAPL dissolution alone at many
      sites. For the hypothetical TCE release, the simulation indicated that
      dissolution of DNAPL would take approximately 38 years, while the back diffusion
      from low permeability zones could maintain the source for an additional 83 years.
      This effect was even more dramatic for the higher solubility DCM (97% of
      longevity due to matrix diffusion), while the lower solubility PCE showed a more
      equal contribution from DNAPL dissolution vs. matrix diffusion. Several methods
      were used to describe the resulting source attenuation curves, including a first
      order decay model which showed that half-life of mass discharge from the matrix
      diffusion dominated phase is in the range of 13 to 29 years for TCE. Because the
      mass discharge rate shifts significantly over time once DNAPL dissolution is
      complete, a Power-Law model was shown to be useful, especially at later stages
      when matrix diffusion dominates. An assessment of mass distribution showed that
      while relatively small percentages of the initial source mass diffused into the
      low permeability compartment, this mass was sufficient to sustain concentrations
      above drinking water standards for decades. These data show that relatively
      typical conditions (e.g., 50-year-old release, moderate to high solubility
      contaminant) are consistent with late stage sources, where mass in low
      permeability matrices serves as the primary source, and fit the conceptual model
      that mass in low permeability zones is important when evaluating source
      longevity.

PMID- 22591741
TI  - Cryopreservation of human vascular umbilical cord cells under good manufacturing
      practice conditions for future cell banks.
AB  - BACKGROUND: In vitro fabricated tissue engineered vascular constructs could
      provide an alternative to conventional substitutes. A crucial factor for tissue
      engineering of vascular constructs is an appropriate cell source. Vascular cells
      from the human umbilical cord can be directly isolated and cryopreserved until
      needed. Currently no cell bank for human vascular cells is available. Therefore,
      the establishment of a future human vascular cell bank conforming to good
      manufacturing practice (GMP) conditions is desirable for therapeutic applications
      such as tissue engineered cardiovascular constructs. MATERIALS AND METHODS: A
      fundamental step was the adaption of conventional research and development
      starting materials to GMP compliant starting materials. Human umbilical cord
      artery derived cells (HUCAC) and human umbilical vein endothelial cells (HUVEC)
      were isolated, cultivated, cryopreserved (short- and long-term) directly after
      primary culture and recultivated subsequently. Cell viability, expression of
      cellular markers and proliferation potential of fresh and cryopreserved cells
      were studied using trypan blue staining, flow cytometry analysis,
      immunofluorescence staining and proliferation assays. Statistical analyses were
      performed using Student's t-test. RESULTS: Sufficient numbers of isolated cells
      with acceptable viabilities and homogenous expression of cellular markers
      confirmed that the isolation procedure was successful using GMP compliant
      starting materials. The influence of cryopreservation was marginal, because
      cryopreserved cells mostly maintain phenotypic and functional characteristics
      similar to those of fresh cells. Phenotypic studies revealed that fresh
      cultivated and cryopreserved HUCAC were positive for alpha smooth muscle actin,
      CD90, CD105, CD73, CD29, CD44, CD166 and negative for smoothelin. HUVEC expressed
      CD31, CD146, CD105 and CD144 but not alpha smooth muscle actin. Functional
      analysis demonstrated acceptable viability and sufficient proliferation
      properties of cryopreserved HUCAC and HUVEC. CONCLUSION: Adaptation of cell
      isolation, cultivation and cryopreservation to GMP compliant starting materials
      was successful. Cryopreservation did not influence cell properties with lasting
      impact, confirming that the application of vascular cells from the human
      umbilical cord is feasible for cell banking. A specific cellular marker
      expression profile was established for HUCAC and HUVEC using flow cytometry
      analysis, applicable as a GMP compliant quality control. Use of these cells for
      the future fabrication of advanced therapy medicinal products GMP conditions are
      required by the regulatory authority.

PMID- 22591742
TI  - Evolutionarily conserved Delta(25(27))-olefin ergosterol biosynthesis pathway in
      the alga Chlamydomonas reinhardtii.
AB  - Ergosterol is the predominant sterol of fungi and green algae. Although the
      biosynthetic pathway for sterol synthesis in fungi is well established and is
      known to use C24-methylation-C24 (28)-reduction (Delta(24(28))-olefin pathway)
      steps, little is known about the sterol pathway in green algae. Previous work has
      raised the possibility that these algae might use a novel pathway because the
      green alga Chlamydomonas reinhardtii was shown to possess a mevalonate
      independent methylerythritol 4-phosphate not present in fungi. Here, we report
      that C. reinhardtii synthesizes the protosterol cycloartenol and converts it to
      ergosterol (C24beta-methyl) and 7-dehydroporiferasterol (C24beta-ethyl) through a
      highly conserved sterol C24- methylation-C25-reduction (Delta(25(27))-olefin)
      pathway that is distinct from the well-described acetate-mevalonate pathway to
      fungal lanosterol and its conversion to ergosterol by the Delta(24(28))-olefin
      pathway. We isolated and characterized 23 sterols by a combination of GC-MS and
      proton nuclear magnetic resonance spectroscopy analysis from a set of mutant,
      wild-type, and 25-thialanosterol-treated cells. The structure and stereochemistry
      of the final C24-alkyl sterol side chains possessed different combinations of
      24beta-methyl/ethyl groups and Delta(22(23))E and Delta(25(27))-double bond
      constructions. When incubated with [methyl-(2)H(3)]methionine, cells incorporated
      three (into ergosterol) or five (into 7-dehydroporiferasterol) deuterium atoms
      into the newly biosynthesized 24beta-alkyl sterols, consistent only with a
      Delta(25(27))-olefin pathway. Thus, our findings demonstrate that two separate
      isoprenoid-24-alkyl sterol pathways evolved in fungi and green algae, both of
      which converge to yield a common membrane insert ergosterol.

PMID- 22591744
TI  - Calix[4]arene derivative bearing imidazole groups as carrier for the transport of
      palladium by using bulk liquid membrane.
AB  - The carrier activity of calix[4]arene containing imidazole groups towards the
      facilitated transport of palladium(II) through dichloromethane bulk liquid
      membrane has been studied. The optimum transport conditions were established by
      the studies on the effect of pH, feed concentration, carrier concentration,
      receiver phase concentration and transport time. A solution of 1M hydrochloric
      acid (HCl) served as receiving phase for maximum transport of the metal ion.
      Maximum transport efficiency was observed for Pd(II) ion when it was present in
      the concentration of 10(-3)M and the transport efficiency after 24h was found as
      95%.

PMID- 22591743
TI  - Metabolomic analysis and identification of a role for the orphan human cytochrome
      P450 2W1 in selective oxidation of lysophospholipids.
AB  - Human cytochrome P450 (P450) 2W1 is still considered an "orphan" because its
      physiological function is not characterized. To identify its substrate
      specificity, the purified recombinant enzyme was incubated with colorectal cancer
      extracts for untargeted substrate searches using an LC/MS-based metabolomic and
      isotopic labeling approach. In addition to previously reported fatty acids, oleyl
      (18:1) lysophosphatidylcholine (LPC, lysolecithin) was identified as a substrate
      for P450 2W1. Other human P450 enzymes tested showed little activity with 18:1
      LPC. In addition to the LPCs, P450 2W1 acted on a series of other
      lysophospholipids, including lysophosphatidylinositol, lysophosphatidylserine,
      lysophosphatidylglycerol, lysophosphatidylethanolamine, and lysophosphatidic acid
      but not diacylphospholipids. P450 2W1 utilized sn-1 18:1 LPC as a substrate much
      more efficiently than the sn-2 isomer; we conclude that the sn-1 isomers of
      lysophospholipids are preferred substrates. Chiral analysis was performed on the
      18:1 epoxidation products and showed enantio-selectivity for formation of
      (9R,10S) over (9S,10R). [corrected]. The kinetics and position specificities of
      P450 2W1-catalyzed oxygenation of lysophospholipids (16:0 LPC and 18:1 LPC) and
      fatty acids (C16:0 and C18:1) were also determined. Epoxidation and hydroxylation
      of 18:1 LPC are considerably more efficient than for the C18:1 free fatty acid.

PMID- 22591745
TI  - Muscle-invasive bladder cancer developing after nephroureterectomy for upper
      urinary tract urothelial carcinoma.
AB  - OBJECTIVES: To evaluate the risk factors and prognosis of muscle-invasive bladder
      cancer (MIBC) developing after nephroureterectomy for upper urinary tract
      urothelial cell carcinoma (UUT-UC). MATERIALS AND METHODS: We reviewed the
      medical records of 422 patients who underwent nephroureterectomy for UUT-UC
      between 1990 and 2010, and identified 173 (40.9%) with intravesical recurrence
      and 28 (6.6%) with MIBC. We evaluated the clinicopathologic features, risk
      factors, and cancer-specific survival (CSS) using the Kaplan-Meier method and the
      Cox proportional hazards regression models. RESULTS: The median intervals from
      nephroureterectomy to intravesical recurrence and the development of MIBC were 8
      and 17 months, respectively. On multivariate analysis, the pathologic stage (>=
      pT3 vs. Ta/T1, HR 5.03, P = 0.001) and ureteral tumor location (HR 2.79, P =
      0.011) were independent risk factors for the development of MIBC, whereas a
      history of previous or concomitant bladder tumor was the only significant risk
      factor for intravesical recurrence. The probability of developing MIBC 5 years
      after nephroureterectomy was 12.6% in patients with 1 risk factor and 20.6% in
      patients with both risk factors. Patients with MIBC had significantly worse CSS
      than those without MIBC (P = 0.004), whereas CSS rates were similar in patients
      with and without intravesical recurrence (P = 0.593). However, stratification
      analysis for matching pathology revealed that CSS rates were not significantly
      different in patients with pT2 or higher stage of UUT-UC. CONCLUSIONS:
      Approximately 5% of the patients developed MIBC after nephroureterectomy with a
      median interval of 17 months. Patients with advanced pathologic stage (>= pT3)
      and a ureteral tumor location are at increased risk of developing MIBC after
      nephroureterectomy.

PMID- 22591746
TI  - Presence of positive surgical margin in patients with organ-confined prostate
      cancer equals to extracapsular extension negative surgical margin. A plea for TNM
      staging system reclassification.
AB  - BACKGROUND: To test the hypothesis that patients with pT2 and positive surgical
      margins (SM) have a similar biochemical-recurrence (BCR) risk to patients with
      pT3a, and negative SM. Moreover, we examined the effect of incorporating positive
      SM as a higher stage on the discrimination accuracy of the current TNM staging
      system. MATERIALS AND METHODS: We evaluated 1,503 prostate cancer patients
      treated with radical prostatectomy, between 1998 and 2010. Only individuals with
      pT2N0 or pT3aN0, without neoadjuvant and/or adjuvant therapy, were included. Cox
      regression analyses tested the relationship between SM status (negative [R0] vs.
      positive [R1]) and BCR rate, after stratification according to T stage.
      Predictive accuracy of the current T stage and of a novel T stage, which consider
      positive SM as a higher stage, was quantified with Harrell's concordance index.
      RESULTS: Positive SM rate was 20.3%. The 5-year BCR rates were 96%, 82%, 78%, and
      62% for patients with, respectively, pT2R0, pT2R1, pT3aR0, and pT3a1 (all P <=
      0.03). In multivariable analyses, the BCR rate was 3.6-, 2.5-, and 6.0-fold
      higher (all P < 0.001) in patients with, respectively, pT2R1, pT3aR0, and pT3aR1
      stage relative to patients with pT2R0 stage. The maximum univariable (14.1%) and
      multivariable (6.9%) discrimination accuracy gains were observed, when tumor
      stage was stratified into pT2R0 vs. pT2R1/pT3R0 vs. pT3R1. CONCLUSIONS: The
      presence of positive SM at radical prostatectomy (RP) specimen substantially
      increases the BCR risk. Patients with pT2R1 have similar BCR risk to patients
      with pT3aR0. Considering these patients as 1 category substantially improves the
      discrimination accuracy of the current TNM staging system.

PMID- 22591747
TI  - Simultaneous progression of oxidative stress, angiogenesis, and cell
      proliferation in prostate carcinoma.
AB  - OBJECTIVES: To understand the association between markers of oxidative stress,
      levels of vascular endothelial growth factor (VEGF), and cell proliferation index
      in relation to disease progression, clinical stage, and cytologic grade in
      pathophysiology of prostate carcinoma. PATIENTS AND METHODS: Case control study
      comprised of 40 prostate carcinoma patients along with 40 age- and sex-matched
      healthy subjects as controls. Levels of 8-hydroxy-2-deoxy guanosine, protein
      carbonyl, and malondialdehyde along with total antioxidant status were measured
      to study the oxidative stress status in the study subjects. Angiogenesis was
      evaluated by studying the VEGF level and cell proliferation index. RESULTS: The
      levels of markers of oxidative stress along with VEGF and cell proliferation
      index were found to be significantly higher with significantly decreased levels
      of antioxidant activity in the study subjects in comparison with healthy
      controls. The results indicate oxidative stress, angiogenesis, and cell
      proliferation activity increase progressively with the increase in staging and
      progression of disease. CONCLUSIONS: Oxidative stress parameters, angiogenesis,
      and cell proliferation activity point clearly that with the progression of
      oxidative stress there is a simultaneous progression of angiogenesis, regulation
      and control of endothelial cell proliferation in relation to disease progression,
      clinical stage, and cytologic grade in the pathophysiology of prostate carcinoma.

PMID- 22591748
TI  - Fas expression in nephrectomized, non-cancerous specimens predicts post
      nephrectomy chronic kidney disease progression in patients with renal and upper
      urinary tract malignancies.
AB  - OBJECTIVES: Despite the surgical curability of renal cell carcinoma (RCC) and
      upper urinary tract urothelial carcinoma (UUT-UC), post-nephrectomy chronic
      kidney disease (CKD) continues to be a cause of concern. We investigated the
      correlation between the expression of apoptotic regulatory molecules in the
      nephrectomized, noncancerous cortex, as well as CKD progression and CKD-related
      mortality. MATERIALS AND METHODS: Fas and Bcl-2 mRNA and protein expression in
      surgically resected specimens from 100 patients with RCC and UUT-UC were
      determined. The estimated glomerular filtration rates (eGFR) were determined
      sequentially before surgery and up to 5 years after surgery. The relationships
      between CKD progression, the expression of these molecules in the renal cortex,
      and the clinical characteristics were analyzed. RESULTS: The mean 1-year
      postoperative percent eGFR decrease was 30.2 (Standard deviation [SD]: 15.2). The
      1-year postoperative percent eGFR decrease greater than the approximate value of
      mean +/- SD (45) was categorized as severe renal functional deterioration (SRFD).
      Glomerular Fas protein expression and a Fas/beta-actin mRNA ratio >0.3 were
      independent predictors for SRFD. Significantly increased mortality rates due to
      cardiovascular events were indicated by glomerular Fas protein expression, Fas
      mRNA levels >0.3, and SRFD. No significant change in Bcl-2 levels was observed.
      CONCLUSIONS: This study is the first report to demonstrate the significance of
      Fas expression in the nephrectomized normal cortex as a predictor of post
      nephrectomy CKD progression. The results from nephrectomized kidney showed that
      the natural course of renal function in the remaining kidney may be affected not
      only by Fas-induced glomerular cell apoptosis but also by the total amount of Fas
      mRNA in cortical cells.

PMID- 22591750
TI  - Acute encephalopathy with a novel point mutation in the SCN2A gene.
AB  - Mutations of the neuronal voltage-gated sodium channel alpha subunit type II
      (SCN2A) cause various epileptic syndromes, but have never been reported in
      association with acute encephalopathy. To validate the involvement of SCN2A
      mutations in acute encephalopathy, we screened 25 patients and found a novel
      missense mutation (Met1128Thr) in a patient with acute encephalitis with
      refractory, repetitive partial seizures (AERRPS). This finding suggests that
      SCN2A mutation is a predisposing factor for acute encephalopathy.

PMID- 22591749
TI  - The prognostic value of transrectal ultrasound guided biopsy in patients over 70
      years old with a prostate specific Antigen (PSA) level <= 15 ng/ml and normal
      digital rectal examination: a 10-year prospective follow-up study of 427
      consecutive patients.
AB  - INTRODUCTION: As a urologist, it is common to review a patient above the age of
      70 being referred to a prostate assessments clinic with an elevated PSA. We
      evaluate the prognosis of these patients clinically as there is no international
      consensus on the exact PSA cutoff level or a single international guideline as to
      when these patients should be offered a prostate biopsy. PATIENTS AND METHODS: On
      receiving ethic committee approval, we recruited 427 consecutive patients aged 70
      years and above referred with a PSA of >= 4 ng/ml, from January 1996 to December
      2000, into our study. All patients were assessed, examined with a digital rectal
      examination (DRE) of the prostate, and a subsequent prostate biopsy. We followed
      up on their histologic diagnosis for up to 10 years and analyzed their outcome.
      The main outcome measures were disease-free survival and overall survival,
      stratified according to the PSA level (<= 15 vs. >15 ng/ml) and DRE findings
      (normal vs. sbnormal). RESULTS: There was a statistically significant difference
      in the overall survival (P value < 0.011) and disease specific survival (P value
      < 0.0001) of cancer patients with a PSA was >15 ng/ml and an abnormal DRE.
      However, in patients with a PSA <= 15 ng/ml and normal DRE, the incidence of
      cancer was low and they had no disease-specific or overall survival benefit.
      CONCLUSIONS: A policy of deferring prostate biopsy in patients with a PSA <= 15
      ng/ml and normal DRE (Group A) would significantly decrease the need of
      unnecessary prostate biopsies. Within this group, patients did not have any
      survival advantage compared with those without cancer. We conclude that up to 20%
      of the prostate biopsies performed in this age group could have been avoided.

PMID- 22591751
TI  - Pilocarpine-induced status epilepticus increases Homer1a and changes mGluR5
      expression.
AB  - Homer1a regulates expression of group I metabotropic glutamate receptors type I
      (mGluR1 and mGluR5) and is involved in neuronal plasticity. It has been reported
      that Homer1a expression is upregulated in the kindling model and hypothesized to
      act as an anticonvulsant. In the present work, we investigated whether
      pilocarpine-induced status epilepticus (SE) would alter Homer1a and mGluR5
      expression in hippocampus. Adult rats were subjected to pilocarpine-model and
      analyzed at 2h, 8h, 24h and 7 d following SE. mRNA analysis showed the highest
      expression of Homer1a at 8h after SE onset, while immunohistochemistry
      demonstrated that Homer1a protein expression was significantly increased in
      hippocampus, amygdala and piriform and entorhinal cortices at 24h after SE onset
      when compared to control animals. The increased Homer1a expression coincided with
      a significant decrease of mGluR5 protein expression in amygdala and piriform and
      entorhinal cortices. The data suggest that during the critical periods of
      epileptogenesis, overexpression of Homer1a occurs to counteract hyperexcitability
      and thus Homer1a may be a molecular target in the treatment of epilepsy.

PMID- 22591752
TI  - Costs, work absence, and adherence in patients with partial onset seizures
      prescribed gabapentin or pregabalin.
AB  - BACKGROUND/OBJECTIVE: Few studies have examined cost of illness of epileptic
      partial onset seizures (POS) from the employer perspective or compared users of
      gabapentin and pregabalin in treatment of POS. This study compares
      pharmacotherapy, direct/indirect costs, and work absences of patients with POS
      newly started on gabapentin or pregabalin. METHODS: Data from employees and
      dependent spouses with POS starting treatment (index date) with either gabapentin
      or pregabalin were analyzed. Patients were required to have at least 6 months of
      health plan enrollment pre- and post-index. Regression modeling compared medical
      and prescription costs, sick leave (SL), short-term disability (STD), workers'
      compensation (WC) costs and absence days during the 6-month post-index period.
      Persistence, adherence (proportion of days covered), impact on adherence of
      copay, and copay as a percent of salary were modeled. RESULTS: Semiannual
      medical, drug, SL, STD, and WC costs for gabapentin vs. pregabalin cohorts were
      $10,306 vs. $9186, $2353 vs. $3387 (P=0.01), $552 vs. $342, $1280 vs. $580, and
      $170 vs. $30, respectively. SL days (10.8 vs. 1.5, P=0.04) and STD days (9.8 vs.
      6.2) were lower in the pregabalin cohort. Persistence (median 94 vs. 70 days) and
      proportion with >= 80% adherence (30% vs. 15%, P=0.049) were greater in the
      pregabalin cohort. Adherence decreased as copay or copay as a percent of salary
      increased beyond specific levels in both cohorts. CONCLUSION: Despite higher
      acquisition costs for branded pregabalin over generic gabapentin, overall direct
      and indirect costs trended lower for pregabalin users. Additionally, pregabalin
      users had significantly fewer sick leave days and significantly higher adherence
      rates than gabapentin users.

PMID- 22591753
TI  - Stereotactic radiofrequency amygdalohippocampectomy for the treatment of temporal
      lobe epilepsy: do good neuropsychological and seizure outcomes correlate with
      hippocampal volume reduction?
AB  - Temporal lobe surgery bears the risk of a decline of neuropsychological
      functions. Stereotactic radiofrequency amygdalohippocampectomy (SAHE) represents
      an alternative to mesial temporal lobe epilepsy (MTLE) surgery. This study
      compared neuropsychological results with MRI volumetry of the residual
      hippocampus. We included 35 patients with drug-resistant MTLE treated by SAHE.
      MRI volumetry and neuropsychological examinations were performed before and 1
      year after SAHE. Each year after SAHE clinical seizure outcome was assessed. One
      year after SAHE 77% of patients were assessed as Engel Class I, 14% of patients
      was classified as Engel II and in 9% of patients treatment failed. Two years
      after SAHE 76% of subjects were classified as Engel Class I, 15% of patients was
      assessed as Engel II and in 9% of patients treatment failed. Hippocampal volume
      reduction was 58+/-17% on the left and 54 +/- 27% on the right side. One year
      after SAHE, intelligence quotients of treated patients increased. Patients showed
      significant improvement in verbal memory (p=0.039) and the semantic long-term
      memory subtest (LTM) (p=0.003). Patients treated on the right side improved in
      verbal memory, delayed recall and LTM. No changes in memory were found in
      patients treated on the left side. There was a trend between the larger extent of
      the hippocampal reduction and improvement in visual memory in speech-side
      operated.

PMID- 22591755
TI  - Golay code modulation in low-power laser-ultrasound.
AB  - The current work presents a correlation-based detection technique with
      application in modulated laser-ultrasonics. In standard use of coded sequences
      the impulse response of a system is recovered in the time domain with improved
      signal to noise ratio (SNR). The presented method is an extension of this
      technique, where the response to a chirped waveform is restored with improved
      SNR; hence, the response is in a well-defined frequency range. To achieve this
      goal the chirped waveforms are modulated by Golay codes. It will be shown that
      the response to this bandlimited carrier waveform can be recovered in the time
      domain with improved signal to noise ratio using a cross-correlation technique.
      Improvement in the SNR is discussed analytically and it is shown that this
      improvement is proportional to the square root of the length of the applied
      sequences. Experimental applications in laser-ultrasound are shown using
      modulated laser diodes as excitation sources with an output power of ~1W. In the
      experiments a plate with a thickness of 50MUm is investigated using Lamb waves in
      the MHz range to confirm the predicted improvement in the SNR. Golay codes with
      three different lengths were used with 7, 9 and 11 bits resulting in 2(7)=128,
      2(9)=512, and 2(11)=2048 repetitions in an individual signal, respectively. The
      predicted improvements of 2 in the SNR between the 7 and 9 bits, and between the
      9 and 11 bits waveforms, respectively, were well approximated by the
      experimentally obtained values of 1.83 and 2.17. As Lamb wave dispersion curves
      can be used for the characterization of plates or layered samples by inverse
      problems, it is also shown that by using multiple measurement points the
      recovered waveforms can be utilized in the evaluation of the dispersion relation.

PMID- 22591754
TI  - Utilization and cost in clinical practice of darbepoetin alfa and epoetin alfa
      for anemia concomitant with chemotherapy.
AB  - BACKGROUND: In 2005, the mean weekly dose ratio of epoetin alfa (EA) to
      darbepoetin alfa (DA) in clinical practice was estimated to be ~400 to 1. In
      2006, a 500-MUg dose and new dosing schedule was approved for DA in the United
      States. In 2007, the warnings and dosing/administration sections were modified
      for both agents. All of these factors may have changed the way that physicians
      use EA and DA. Previous studies of the use of erythropoiesis-stimulating agents
      (ESAs) in patients with anemia concomitant with chemotherapy may thus not reflect
      current clinical practice. OBJECTIVE: The goal of this study was to examine the
      use and costs of ESAs in clinical practice in patients with anemia concomitant
      with chemotherapy. METHODS: Using 2 large US health care claims databases, all
      adults (aged >=18 years) were identified who received ESAs in 2008 and had
      evidence of receipt of chemotherapy <=42 days before initial ESA receipt (ie, the
      index date). Episodes of care were defined as beginning on the index date and
      ending on the date of the last ESA claim that was followed by a >=42-day gap
      without any receipt of ESAs, to which was added an assumed duration of clinical
      benefit (in days) based on the ESA and corresponding dose received. DA- and EA
      treated patients were matched using propensity scoring. The mean weekly dose and
      cost of DA and EA during episodes of care was calculated using all information
      from relevant claims noted during such episodes. Each database was analyzed
      separately. RESULTS: In the first database, 475 patients with DA episodes of care
      were matched to an equal number of patients with EA episodes; in the second
      database, there were 424 matched pairs. In the first database, the mean (95% CI)
      weekly dose was 37,444 U (35,942 U-39,001 U) during EA episodes and 110 MUg (108
      MUg-113 MUg) during DA episodes; the mean weekly EA/DA dose ratio was 340 to 1.
      In the second database, the mean (95% CI) weekly dose was 37,047 U (35,944 U
      38,175 U) during EA episodes and 121 MUg (117 MUg-125 MUg) during DA episodes;
      the mean weekly EA/DA dose ratio was 306 to 1. CONCLUSIONS: The mean weekly EA/DA
      dose ratio during episodes of ESA care has declined in patients with anemia
      concomitant with chemotherapy, due at least in part to the availability and use
      of a new dose/dosing schedule for DA without similar changes for EA.

PMID- 22591756
TI  - MYOD-1 in normal colonic mucosa--role as a putative biomarker?
AB  - BACKGROUND: DNA methylation of promoter-associated CpG islands of certain genes
      may play a role in the development of colorectal cancer. The MYOD-1 gene which is
      a muscle differentiation gene has been showed to be significantly methylated in
      colorectal cancer which, is an age related event. However the role of this gene
      in the colonic mucosa is not understood and whether methylation occurs in
      subjects without colon cancer. In this study, we have determined the frequency of
      methylation of the MYOD-1 gene in normal colonic mucosa and investigated to see
      if this is associated with established colorectal cancer risk factors primarily
      ageing. RESULTS: We analysed colonic mucosal biopsies in 218 normal individuals
      and demonstrated that in most individuals promoter hypermethylation was not
      quantified for MYOD-1. However, promoter hypermethylation increased significantly
      with age (p<0.001 using regression analysis) and this was gender independent. We
      also showed that gene promoter methylation increased positively with an increase
      in waist to hip (WHR) ratio - the latter is also a known risk factor for colon
      cancer development. CONCLUSIONS: Our study suggests that promoter gene
      hypermethylation of the MYOD-1 gene increases significantly with age in normal
      individuals and thus may offer potential as a putative biomarker for colorectal
      cancer.

PMID- 22591757
TI  - Information seeking for making evidence-informed decisions: a social network
      analysis on the staff of a public health department in Canada.
AB  - BACKGROUND: Social network analysis is an approach to study the interactions and
      exchange of resources among people. It can help understanding the underlying
      structural and behavioral complexities that influence the process of capacity
      building towards evidence-informed decision making. A social network analysis was
      conducted to understand if and how the staff of a public health department in
      Ontario turn to peers to get help incorporating research evidence into practice.
      METHODS: The staff were invited to respond to an online questionnaire inquiring
      about information seeking behavior, identification of colleague expertise, and
      friendship status. Three networks were developed based on the 170 participants.
      Overall shape, key indices, the most central people and brokers, and their
      characteristics were identified. RESULTS: The network analysis showed a low
      density and localized information-seeking network. Inter-personal connections
      were mainly clustered by organizational divisions; and people tended to limit
      information-seeking connections to a handful of peers in their division. However,
      recognition of expertise and friendship networks showed more cross-divisional
      connections. Members of the office of the Medical Officer of Health were located
      at the heart of the department, bridging across divisions. A small group of
      professional consultants and middle managers were the most-central staff in the
      network, also connecting their divisions to the center of the information-seeking
      network. In each division, there were some locally central staff, mainly
      practitioners, who connected their neighboring peers; but they were not
      necessarily connected to other experts or managers. CONCLUSIONS: The methods of
      social network analysis were useful in providing a systems approach to understand
      how knowledge might flow in an organization. The findings of this study can be
      used to identify early adopters of knowledge translation interventions, forming
      Communities of Practice, and potential internal knowledge brokers.

PMID- 22591758
TI  - Outcome of breast lesions detected at screening ultrasonography.
AB  - OBJECTIVE: To assess the final outcome of breast lesions detected during
      screening ultrasonography (US) and categorized by BI-RADS final assessment.
      MATERIALS AND METHODS: During a 1-year period, 3817 consecutive asymptomatic
      women with negative findings at both clinical breast examinations and mammography
      underwent bilateral whole breast US and BI-RADS categories were provided for US
      detected breast lesions. The reference standard was a combination of histology
      and US follow-up (>=12 months), and the final outcomes of 1192 US-detected
      lesions were analyzed. RESULTS: Of 904 category 2 lesions, 890 remained stable
      for 12-60 months. Biopsies of 14 lesions revealed no malignancies (NPV=100%). Of
      247 category 3 lesions, 232 remained stable for 12-60 months. Biopsies of 15
      lesions revealed 2 malignancies, which were diagnosed within 6 months of the
      index examination and were node negative (NPV=99.2%). Of 41 category 4 lesions,
      biopsies of 38 lesions revealed 5 malignancies (PPV=12.2%), and 3 remained stable
      for 37-51 months. No US-detected lesion was classified as category 5. CONCLUSION:
      The rates of malignancy for US-detected BI-RADS categories 2, 3, and 4 lesions
      were 0%, 0.8%, and 12.2%, respectively. The final assessment of US BI-RADS
      categorization showed it to be an appropriate predictor of malignancy for
      screening US-detected breast lesions.

PMID- 22591759
TI  - Three-dimensional delayed gadolinium-enhanced magnetic resonance imaging of hip
      joint cartilage at 3T: a prospective controlled study.
AB  - PURPOSE: To assess acetabular and femoral hip joint cartilage with three
      dimensional (3D) delayed gadolinium-enhanced magnetic resonance imaging (dGEMRIC)
      in patients with degeneration of hip joint cartilage and asymptomatic controls
      with morphologically normal appearing cartilage. METHODS AND MATERIALS: A total
      of 40 symptomatic patients (18 males, 22 females; mean age: 32.8+/-10.2 years,
      range: 18-57 years) with different hip joint deformities including
      femoroacetabular impingement (n=35), residual hip dysplasia (n=3) and coxa magna
      due to Legg-Calve-Perthes disease in childhood (n=2) underwent high-resolution 3D
      dGEMRIC for the evaluation of acetabular and femoral hip joint cartilage. Thirty
      one asymptomatic healthy volunteers (12 males, 19 females; mean age: 24.5+/-1.8
      years, range: 21-29 years) without underlying hip deformities were included as
      control. MRI was performed at 3 T using a body matrix phased array coil. Region
      of interest (ROI) analyses for T1Gd assessment was performed in seven regions in
      the hip joint, including anterior to superior and posterior regions. RESULTS:
      T1Gd mapping demonstrated the typical pattern of acetabular cartilage consistent
      with a higher glycosaminoglycan (GAG) content in the main weight-bearing area.
      T1Gd values were significantly higher in the control group than in the patient
      group whereas significant differences in T1Gd values corresponding to the amount
      of cartilage damage were noted both in the patient group and in the control
      group. CONCLUSIONS: Our study demonstrates the potential of high-resolution 3D
      dGEMRIC at 3 T for separate acetabular and femoral hip joint cartilage assessment
      in various forms of hip joint deformities.

PMID- 22591760
TI  - Multiphase CT scanning and different intravenous contrast media concentrations in
      combined F-18-FDG PET/CT: Effect on quantitative and clinical assessment.
AB  - PURPOSE: To evaluate the influence of multiphase CT scanning and different
      intravenous contrast media on contrast enhancement, attenuation correction and
      image quality in combined PET/CT. MATERIAL AND METHODS: 140 patients were
      prospectively enrolled for F-18-FDG-PET/CT including a low-dose unenhanced,
      arterial and venous contrast enhanced CT. The first (second) 70 patients,
      received contrast medium with 370 (300) mg iodine/ml. The iodine delivery rate
      (1.3mg/s) and total iodine load (44.4g) were identical for both groups. Contrast
      enhancement and maximum and mean standardized FDG uptake values (SUVmax and
      SUVmean) were determined for the un-enhanced, arterial and venous PET/CT at
      multiple anatomic sites and PET reconstructions were visually evaluated. RESULTS:
      Arterial contrast enhancement was significantly higher for the 300mg/ml contrast
      medium compared to 370mgI/ml at all anatomic sites. Venous enhancement was not
      different between the two contrast media. SUVmean and SUVmax were significantly
      higher for the contrast enhanced compared to the non-enhanced PET/CT at all
      anatomic sites (all P<0.001). Tracer uptake was significantly higher in the
      arterial than in the venous PET/CT in the arteries using both contrast media (all
      P<0.001). No differences in tracer uptake were found between the contrast media
      (all P>0.05). Visual assessment revealed no relevant differences between the
      different PET reconstructions. CONCLUSIONS: There is no relevant qualitative
      influence on the PET scan from the use of different intravenous contrast media in
      its various phases in combined multiphase PET/CT. For quantitative analysis of
      tracer uptake it is required to use an identical PET/CT protocol.

PMID- 22591761
TI  - Elastography ultrasound and questionable breast lesions: does it count?
AB  - OBJECTIVE: To check possible additional value of using elastography ultrasound in
      the specification of questionable breast lesions. SUBJECTS AND METHODS:
      Questionable breast lesions on gray scale ultrasound examination had been further
      evaluated by elastography ultrasound in 97 cases with median age of 42 years. The
      studied lesions were pathologically proven (58 benign and 39 malignant) using
      true cut tissue/surgical excision biopsy that was considered the gold standard of
      reference. RESULTS: Conventional ultrasound categorization before biopsy
      included: category 3 (probably benign) in 42.3% (n=41), category 4a (low
      suspicion of malignancy) in 13.4% (n=13), category 4b (intermediate suspicion of
      malignancy) in 16.5% (n=16) and category 4c (moderate suspicion of malignancy) in
      27.8% (n=27). We had evaluated elastography ultrasound regarding elastography
      strain scoring and quantitative strain ratio. Sensitivity, specificity and
      accuracy were 89.7%, 86.2% and 87.6% for conventional ultrasound, 92.3%, 74.1%
      and 81.4% for elastogram 5-point scoring method and 87.1%, 89.6% and 88.6% for
      the calculated strain ratios respectively in the assessment of the examined
      breast lesions. CONCLUSION: Ultrasound elastography, using both qualitative and
      quantitative methods can improve the performance of conventional B-mode
      ultrasound and enhance its specificity and accuracy in the diagnosis of
      questionable (BI-RADS categories 3 and 4) breast lesions.

PMID- 22591762
TI  - Validating a low cost approach for predicting human responses to emergency
      situations.
AB  - This paper presents a new approach for predicting human responses to emergency
      situations. The approach was developed for ergonomists working in emergency
      response preparedness. It involves presenting participants with a description of
      a hypothetical emergency scenario before asking them to describe how they would
      respond. This study builds upon previous investigations (Lawson et al., 2009a,
      2009b; Lawson, 2011) which demonstrated significant associations between the
      predicted behaviour and that reported in a reference study of behaviour in real
      fires. This further work aimed to evaluate in greater detail the validity,
      reliability, resources and ethics of the approach. The results demonstrated
      significant relationships between the predicted behaviours and those from the
      reference study for both frequencies (r(s) = 0.572, N = 51, p < 0.001) and
      sequences (r(s) = 0.344, N = 40, p < 0.05) of behaviour. The approach is shown to
      be replicable and requires low resources. It does not present any notable risk of
      physical injury.

PMID- 22591763
TI  - The smooth (tractor) operator: insights of knowledge engineering.
AB  - The design of and training for complex systems requires in-depth understanding of
      task demands imposed on users. In this project, we used the knowledge engineering
      approach (Bowles et al., 2004) to assess the task of mowing in a citrus grove.
      Knowledge engineering is divided into four phases: (1) Establish goals. We
      defined specific goals based on the stakeholders involved. The main goal was to
      identify operator demands to support improvement of the system. (2) Create a
      working model of the system. We reviewed product literature, analyzed the system,
      and conducted expert interviews. (3) Extract knowledge. We interviewed tractor
      operators to understand their knowledge base. (4) Structure knowledge. We
      analyzed and organized operator knowledge to inform project goals. We categorized
      the information and developed diagrams to display the knowledge effectively. This
      project illustrates the benefits of knowledge engineering as a qualitative
      research method to inform technology design and training.

PMID- 22591764
TI  - Proximal balloon deflation technique: a novel method to retrieve retained or
      entrapped equipment from the coronary system.
AB  - Complications of retained or entrapped equipment in the coronary system are still
      encountered during angioplasty procedures. Although these complications are rare,
      it is extremely difficult to retrieve such equipments. We report on two cases
      that a retained IVUS catheter or an entrapped filter wire were retrieved from the
      coronary system using more simplified technique that does not involve in the
      usage of snare or any other retrieval tool. After placing an additional guidewire
      and balloon alongside an equipment, it was easily retrieved from the coronary
      system just after the proximal balloon deflation.

PMID- 22591765
TI  - The surgical management of severe macroglossia in systemic AL amyloidosis.
AB  - Amyloidosis is a disease characterised by the deposition in body tissues of
      amyloid: abnormal protein in a beta pleated sheet formation. It is a systemic
      disorder and macroglossia may be seen in all forms. Changes to the normal
      architecture of the tissues and systemic features of the disease and its
      underlying cause can complicate the surgical management of the enlarged tongue.

PMID- 22591766
TI  - Supraclavicular metastases from distant primaries: what is the role of the head
      and neck surgeon?
AB  - Suspicious malignant supraclavicular lymphadenopathy provides a challenge for
      diagnosis and treatment. The wide variety of primary tumours that metastasise to
      this region should alert the clinician to look beyond the head and neck,
      particularly if it is the only site in the neck with suspected disease. As
      metastatic spread to these nodes from primaries not in the head and neck often
      indicates wide spread disease, neck dissection is controversial. In this article
      we review the lymphatic anatomy and discuss the investigation of supraclavicular
      lymphadenopathy. We discuss the evidence for the management of the neck in
      patients with subclavicular primary cancers (excluding lymphoma and melanoma) and
      the role of neck dissection.

PMID- 22591767
TI  - Rapid urbanization and the growing threat of violence and conflict: a 21st
      century crisis.
AB  - As the global population is concentrated into complex environments, rapid
      urbanization increases the threat of conflict and insecurity. Many fast-growing
      cities create conditions of significant disparities in standards of living, which
      set up a natural environment for conflict over resources. As urban slums become a
      haven for criminal elements, youth gangs, and the arms trade, they also create
      insecurity for much of the population. Specific populations, such as women,
      migrants, and refugees, bear the brunt of this lack of security, with significant
      impacts on their livelihoods, health, and access to basic services. This lack of
      security and violence also has great costs to the general population, both
      economic and social. Cities have increasingly become the battlefield of recent
      conflicts as they serve as the seats of power and gateways to resources.
      International agencies, non-governmental organizations, and policy-makers must
      act to stem this tide of growing urban insecurity. Protecting urban populations
      and preventing future conflict will require better urban planning, investment in
      livelihood programs for youth, cooperation with local communities, enhanced
      policing, and strengthening the capacity of judicial systems.

PMID- 22591768
TI  - ScolioMedIS: web-oriented information system for idiopathic scoliosis
      visualization and monitoring.
AB  - Adolescent idiopathic scoliosis is the most common type of abnormal curvature
      observed in spine and it progresses rapidly during the puberty period. The most
      followed clinical way of assessing the spinal deformity is subjective by
      measuring the characteristic angles of spinal curve from a set of radiographic
      images. This paper presents a web-based information system (called ScolioMedIS)
      based on parameterized 3D anatomical models of the spine to quantitatively assess
      the deformity and to minimize the amount of radiation exposure by reducing the
      number of radiographs required. The main components of the system are 3D
      parametric solid model of spine, back surfaces, relevant clinical information and
      scoliosis ontology. The patient-specific spine model is regenerated from the
      parametric model and surface data using anatomical information extracted from
      radiographic images. The system is designed to take inherent advantage of Web for
      facilitating multi-center data collection and collaborative clinical decisions.
      The preliminary analysis of patient data showed promising results, which involve
      improved documentation standard, clinical decision knowledge base record,
      facilitated exchange and retrieval of medical data between institutions in multi
      center clinical studies, 3D visualization of spinal deformity, and permanent
      monitoring of treatments.

PMID- 22591769
TI  - An optimal closed-loop control strategy for mechanical chest compression devices:
      a trade-off between the risk of chest injury and the benefit of enhanced blood
      flow.
AB  - OBJECTIVES: The widespread application of chest compression (CC) as a first aid
      measure inevitably has the potential for both harm and benefit. The present study
      was therefore undertaken to design an optimal CC closed-loop control strategy
      (OCCCS) for mechanical CC devices that will present an effective trade-off
      between the risk of chest injury and the benefit of blood flow during CPR.
      Additionally, to evaluate the CC performance of the OCCCS, the differences
      between the OCCCS and the traditional mechanical CC method (TMCM) of performing
      standard CC were explored. METHODS: Using the computer simulation technique,
      partial pressure of end-tidal CO2 (PETCO2) and human chest stiffness are
      simulated based on the Babbs' model in present study. PETCO2 was regarded as a
      benefit factor (BF), which was divided into 3 levels, while chest stiffness was
      regarded as a risk factor (RF), which was divided into 4 levels. A benefit versus
      risk index (BRI) was also constructed for the comprehensive evaluation of risk
      and benefit. An OCCCS was developed with the combination of the BF, RF, BRI and
      fuzzy control strategy. A comparison between the OCCCS and TMCM was then
      performed based on computer simulations. RESULTS: The OCCCS obtained a greater
      BRI and a better trade-off between risk and benefit than the TMCM in 6 out of a
      total 9 cases, and the OCCCS also resulted in a significantly improved cardiac
      output (CO) and PETCO2 in 6 of the 9 cases. The mean BRI, CO and PETCO2 resulting
      from the OCCCS were 5.69, 1.45 L/min and 15.51 mmHg, respectively, while the mean
      BRI, CO and PETCO2 resulting from TMCM were 4.76, 1.18 L/min and 13.26 mmHg,
      respectively. CONCLUSIONS: The OCCCS can provide safer and more effective CC
      during cardiopulmonary resuscitation (CPR) compared to the TMCM, and has great
      potential in the future mechanical CC device development.

PMID- 22591770
TI  - Tear film aberration dynamics and vision-related quality of life in patients with
      dry eye disease.
AB  - OBJECTIVE: Corneal and ocular wavefront aberrations were recorded together with
      clinical examination results and patient-reported vision-related quality-of-life
      evaluation results to define the relevance of dynamic optical analysis of the eye
      in dry eye disease (DED). DESIGN: Prospective and comparative clinical study.
      PARTICIPANTS: Forty DED patients and 40 age- and gender-matched control subjects.
      METHODS: Serial measurements of ocular and corneal higher-order aberrations
      (HOAs) after blink were performed for 10 seconds using the KR-1 aberrometer
      (Topcon, Clichy, France). Vision-related health-targeted quality of life was
      evaluated using the Ocular Surface Disease Index (OSDI) questionnaire. The
      clinical examination included tear film assessment (tear film break-up time and
      Schirmer I test), ocular surface damage assessment with the Oxford and van
      Bijsterveld indexes, and Meibomian dysfunction grading. Tear osmolarity also was
      measured. MAIN OUTCOME MEASURES: The time course of HOAs and modulation transfer
      function (MTF) was compared between groups and was analyzed in comparison with
      the OSDI and clinical data in DED patients. RESULTS: The root mean square of
      ocular and corneal total HOAs, particularly third-order aberrations,
      significantly increased over the 10-second period in DED patients, whereas no
      change occurred in controls. Analysis of MTF revealed progressive degradation of
      ocular optical quality resulting from loss of contrast at intermediate and high
      spatial frequencies in DED patients compared with controls. The progression index
      for corneal HOAs was correlated with the subjective index of patient-reported
      visual outcomes and with objective clinical findings of tear film and ocular
      surface damage. CONCLUSIONS: Objective measurement of the time course of HOAs may
      constitute a new single instrument to evaluate and manage patients with DED
      because it reliably reflects the completeness of the disease.

PMID- 22591772
TI  - Abstracts of the 15th Annual SCMR (Society for Cardiovascular Magnetic Resonance)
      Scientific Sessions. Orlando, Florida, USA. February 2-5, 2012.

PMID- 22591771
TI  - Value of serum and bronchoalveolar fluid lavage pro- and anti-inflammatory
      cytokine levels for predicting bronchopulmonary dysplasia in premature infants.
AB  - OBJECTIVE: The aim of this study was to determine the value of pro- and anti
      inflammatory cytokine levels in both blood and tracheal aspirate (TA) samples
      that were obtained within 24 h after birth for predicting bronchopulmonary
      dysplasia (BPD) development in premature infants. MATERIAL AND METHODS: Premature
      infants, who were born before 32 weeks of gestation, weighing less than 1,500 g,
      and admitted with respiratory distress between September 2009 and December 2010,
      were enrolled. Tracheal aspirate samples and serum were obtained from all infants
      on the first day of admittance for evaluation of pro- and anti-inflammatory
      cytokine levels using ELISA. RESULTS: The study included 102 premature babies of
      whom 31 (30%) had BPD diagnosed in the follow-up. Mild, moderate and severe BPD
      was diagnosed in 10 (32%), 14 (45%) and seven (23%) infants, respectively. Both
      serum and TA sample pro-inflammatory cytokine (TNF-alpha, IL-1beta, IL-6) levels
      were significantly higher, and anti-inflammatory cytokine (IL-10) levels were
      significantly lower in infants who developed BPD compared with those who had no
      BPD. No significant differences were detected in either serum or TA sample pro-
      and anti-inflammatory cytokine concentrations in preterm infants with BPD in
      terms of BPD severity. Cut-off values of both serum and TA sample pro- and anti
      inflammatory cytokine concentrations for predicting BPD were also determined.
      CONCLUSION: It is suggested that higher serum and TA pro-inflammatory cytokine
      (TNF-alpha, IL-1beta, IL-6) concentrations, along with lower anti-inflammatory
      cytokine (IL-10) concentrations, might be used for predicting the development of
      BPD in premature infants with respiratory distress at birth.

PMID- 22591773
TI  - Polymorphism in the MSX1 gene in a family with upper lateral incisor agenesis.
AB  - OBJECTIVE: The MSX1 gene plays a key role in odontogenesis regulation,
      particularly during early stages. Since only a few genetic variants have thus far
      been associated with non-syndromic tooth agenesis, we screened for mutations in
      this gene, aiming to detect a relationship between genotype and phenotype.
      DESIGN: The sample consisted of one proband with non-syndromic hypodontia
      involving upper lateral incisors, three relatives and ten unaffected controls.
      The proband and two affected relatives showed the same phenotype. DNA was
      extracted from buccal epithelial cells, and direct sequencing was performed. The
      two exons of MSX1 were first sequenced in the proband. When an alteration was
      detected, his relatives were investigated by the same method. RESULTS: We
      identified the known polymorphism *6C>T in the homozygous state in all three
      affected family members. The unaffected father was heterozygous and ten control
      samples were negative for the *6C>T polymorphism. CONCLUSIONS: The *6C>T
      polymorphism, when homozygous, may contribute to agenesis of upper lateral
      incisors. However, since the *6C>T polymorphism is quite common, additional genes
      must be involved in this phenotype.

PMID- 22591775
TI  - Human rights violations among sexual and gender minorities in Kathmandu, Nepal: a
      qualitative investigation.
AB  - BACKGROUND: Nepal has experienced sporadic reports of human rights violations
      among sexual and gender minorities. Our objective was to identify a range of
      human rights that are enshrined in international law and/or are commonly reported
      by sexual and gender minority participants in Kathmandu, to be nonprotected or
      violated. METHODS: In September 2009 three focus group discussions were conducted
      by trained interviewers among a convenience sample of sexual and gender minority
      participants in Kathmandu Nepal. The modified Delphi technique was utilized to
      elicit and rank participant-generated definitions of human rights and their
      subsequent violations. Data was analyzed independently and cross checked by
      another investigator. RESULTS: Participants (n = 29) reported experiencing a
      range of human rights violations at home, work, educational, health care settings
      and in public places. Lack of adequate legal protection, physical and mental
      abuse and torture were commonly reported. Access to adequate legal protection and
      improvements in the family and healthcare environment were ranked as the most
      important priority areas. CONCLUSIONS: Sexual and gender minorities in Nepal
      experienced a range of human rights violations. Future efforts should enroll a
      larger and more systematic sample of participants to determine frequency, timing,
      and/or intensity of exposure to rights violations, and estimate the population
      based impact of these rights violations on specific health outcomes.

PMID- 22591774
TI  - PPARgamma inhibits inflammation and RANKL expression in epoxy resin-based sealer
      induced osteoblast precursor cells E1 cells.
AB  - OBJECTIVES: The AH26 of epoxy resin-based sealer is used widely owing to its
      excellent physical characteristics but it induces oxidative stress and
      cytotoxicity at the periapical tissues. AH26 exhibited cytotoxicity towards MC
      3T3-E1 cells, which resulted in mitochondria-mediated apoptosis. Peroxisome
      proliferator-activated receptor (PPARgamma) has an anti-inflammatory effect in
      several tissue and cells, but its action of AH26-related inflammation is not
      completely understood. The aim of this study is to investigate the anti
      inflammatory and anti-osteoclastic mechanisms of PPARgamma in AH26-induced MC-3T3
      E1 cells. METHODS: AH26 was prepared according to the manufacturer's
      instructions. The 1-day extraction sample, which was diluted by 30%, was tested
      in this experiment. Recombinant deficiency adenoviral PPARgamma (Ad/PPARgamma)
      was used to examine PPARgamma over-expression in MC-3T3 E1 cells. AH26-induced
      reactive oxygen species (ROS) formation was analysed using 2',7'
      dichlorodihydrofluorescein diacetate (DCFH-DA) with fluorescence-activated cell
      sorting (FACS), and the expression of receptor activator of nuclear factor-kappaB
      ligand (RANKL) and inflammatory molecules was determined by immunoblotting. The
      anti-inflammatory and anti-osteoclastic mechanisms of the PPARgamma-involved
      signal pathway was examined by immunoblotting. RESULTS: The AH26 elutes induced
      inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), RANKL
      expression and ROS formation. In addition, the AH26 elutes suppressed the
      expression of PPARgamma. However, the recovery of PPARgamma expression with
      Ad/PPARgamma resulted in the inhibition of iNOS, COX-2, RANKL and ROS formation
      despite the AH26 treatment in MC-3T3 E1 cells. The mechanism of PPARgamma was
      confirmed by the blocking of nuclear factor kappa B (NF-kappaB) translocation to
      the nucleus after the suppression of ERK1/2, SAPK/JNK and AP-1 in AH26-induced MC
      3T3 E1 cells. CONCLUSION: From this result, PPARgamma acts to inhibit bone
      destruction in AH26-induced bone cells. Therefore, the anti-inflammatory and anti
      osteoclastic character of PPARgamma might be applicable for healing periapical
      lesions more rapidly or reducing the induction of cellular inflammation caused by
      some endodontic sealers.

PMID- 22591776
TI  - Value generation and health reform in emergency medical services.
AB  - American Emergency Medical Services (EMS) agencies largely have been untouched by
      the dramatic health care reform efforts underway, although change seems imminent.
      Clarifying the role of the modern EMS system, and the yardsticks used to evaluate
      its performance, will be a challenge.This paper introduces the concept of value
      (or outcomes to cost ratio) in EMS, and offers value assessment as a means by
      which reform decisions can be framed. The best reform decisions are those that
      optimize both costs and outcomes. This includes: (1) attention to the patient
      experience; (2) disallowing the provision of unhelpful, harmful or disproven
      prehospital care; and (3) expanding patient dispositions beyond Emergency
      Departments. Costs of care will need to be tracked carefully and acknowledged.
      Value generation should serve as the goal of ongoing EMS reform efforts.

PMID- 22591777
TI  - Optimization of immune responses induced by therapeutic vaccination with cross
      reactive antigens in a humanized hepatitis B surface antigen transgenic mouse
      model.
AB  - The absence of relevant animal models of chronic hepatitis B virus (HBV)
      infection has hampered the evaluation and development of therapeutic HBV
      vaccines. In this study, we generated a novel transgenic mouse lineage that
      expresses human class I and II HLA molecules and the hepatitis B surface antigen
      (HBsAg). HBsAg and hepatitis B core antigen (HBcAg) administered as plasmid DNAs
      and recombinant proteins, either alone or in combination, were evaluated as
      therapeutic vaccine candidates in this mouse model. Our results emphasize the
      importance of the route of administration in breaking HBsAg tolerance. Although
      immunizing the transgenic mice with DNA encoding homologous HBsAg was sufficient
      to induce CD8+ T-cell responses, HBsAg from a heterologous subtype was required
      to induce a CD4+ T-cell response. Importantly, only prime-boost immunization
      protocols that combined plasmid DNA injection followed by protein injection
      induced the production of antibodies against the HBsAg expressed by the
      transgenic mice.

PMID- 22591778
TI  - Olfaction and schizophrenia clinical risk status: just the facts.

PMID- 22591779
TI  - Illicit drug use in heavy smokers with and without schizophrenia.
AB  - OBJECTIVE: The prevalence of cigarette smoking among people with schizophrenia is
      greater than that of the general population. Because smoking and use of other
      drugs covary, we examined illicit drug use in current smokers not trying to quit
      or reduce their tobacco use. We recruited outpatient participants who had a DSM
      IV diagnosis of schizophrenia or schizoaffective disorder (schizophrenia, n=70)
      and a control group who had no Axis I psychiatric disorders (control, n=97).
      During a 2-3-hour session, participants completed demographic and research
      questionnaires, including the Drug Use Survey (DUS). RESULTS: Participants with
      schizophrenia were older than controls (p<0.001) and smoked more cigarettes per
      day (p=0.01), but did not differ in degree of nicotine dependence. Ever using a
      drug was similar between the groups, except that significantly more participants
      with schizophrenia reported ever using hallucinogens (p<0.001) and inhalants
      (p=0.001). For alcohol, cocaine, and marijuana, fewer participants with
      schizophrenia were current users, but more participants with schizophrenia were
      past users (ps<0.0001). Heavy smokers from the general population continued to
      use illicit drugs throughout their lives, while schizophrenia participants had
      the highest period of illicit drug use in their 20s. CONCLUSIONS: These data
      suggest that illicit drug use tends to be high in heavy cigarette smokers,
      regardless of a schizophrenia diagnosis. However, while illicit drug use is high
      across the lifespan of heavy smokers in the general population, heavy smokers
      with schizophrenia use illicit drugs mostly in the first decade of their illness.

PMID- 22591780
TI  - A dual change model of life satisfaction and functioning for individuals with
      schizophrenia.
AB  - Despite the notion that increases in functioning should be associated with
      increases in life satisfaction in schizophrenia, research has often found no
      association between the two. Dual change models of global and domain-specific
      life satisfaction and functioning were examined in 145 individuals with
      schizophrenia receiving community-based services over 12 months. Functioning and
      satisfaction were measured using the Role Functioning Scale and Satisfaction with
      Life Scale. Data were analyzed using latent growth curve modeling. Improvement in
      global life satisfaction was associated with improvement in overall functioning
      over time. Satisfaction with living situation also improved as independent
      functioning improved. Work satisfaction did not improve as work functioning
      improved. Although social functioning improved, satisfaction with social
      relationships did not. The link between overall functioning and global life
      satisfaction provides support for a recovery-based orientation to community based
      psychosocial rehabilitation services. When examining sub-domains, the link
      between outcomes and subjective experience suggests a more complex picture than
      previously found. These findings are crucial to interventions and programs aimed
      at improving functioning and the subjective experiences of consumers recovering
      from mental illness. Interventions that show improvements in functional outcomes
      can assume that they will show concurrent improvements in global life
      satisfaction as well and in satisfaction with independent living. Interventions
      geared toward improving social functioning will need to consider the complexity
      of social relationships and how they affect satisfaction associated with personal
      relationships. Interventions geared towards improving work functioning will need
      to consider how the quality and level of work affect satisfaction with
      employment.

PMID- 22591781
TI  - Day-to-day variability in spot urine protein-creatinine ratio measurements.
AB  - BACKGROUND: Accurate measurement of proteinuria is important in the diagnosis and
      management of chronic kidney disease (CKD). The reference standard test, 24-hour
      urinary protein excretion, is inconvenient and vulnerable to collection errors.
      Spot urine protein-creatinine ratio (PCR) is a convenient alternative and is in
      widespread use. However, day-to-day variability in PCR measurements has not been
      evaluated. STUDY DESIGN: Prospective cohort study of day-to-day variability in
      spot urine PCR measurement. SETTING & PARTICIPANTS: Clinically stable outpatients
      with CKD (n = 145) attending a university hospital CKD clinic in Australia
      between July 2007 and April 2010. INDEX TEST: Spot urine PCR. OUTCOMES: Spot PCR
      variability was assessed and repeatability limits were determined using
      fractional polynomials. MEASUREMENTS: Spot PCRs were measured from urine samples
      collected at 9:00 am on consecutive days and 24-hour urinary protein excretion
      was collected concurrently. RESULTS: Paired results were analyzed from 145
      patients: median age, 56 years; 59% men; and median 24-hour urinary protein
      excretion, 0.7 (range, 0.06-35.7) g/d. Day-to-day variability was substantial and
      increased in absolute terms, but decreased in relative terms with increasing
      baseline PCR. For patients with a low baseline PCR (20 mg/mmol [177 mg/g]), a
      change greater than +/-160% (repeatability limits, 0-52 mg/mmol [0-460 mg/g]) is
      required to indicate a real change in proteinuria status with 95% certainty,
      whereas for those with a high baseline PCR (200 mg/mmol [1,768 mg/g]), a change
      of +/-50% (decrease to <100 mg/mmol [<884 mg/g] or increase to >300 mg/mmol
      [>2,652 mg/g]) represents significant change. LIMITATIONS: These study results
      need to be replicated in other ethnic groups. CONCLUSIONS: Changes in PCR
      observed in patients with CKD, ranging from complete resolution to doubling of
      PCR values, could be due to inherent biological variation and may not indicate a
      change in disease status. This should be borne in mind when using PCR in the
      diagnosis and management of CKD.

PMID- 22591782
TI  - Decoding the informational properties of the RNA polymerase II Carboxy Terminal
      Domain.
AB  - BACKGROUND: The largest sub-unit of RNA polymerase II, Rpb1p, has long been known
      to be subject to post-translational modifications that influence various aspects
      of pre-mRNA processing. However, the portion of the Rpb1p molecule subject to
      these modifications - the carboxy-terminal domain or CTD - remains the subject of
      much fascination. Intriguingly, the CTD possesses a unique repetitive structure
      consisting of multiple repeats of the heptapeptide sequence,
      Y(1)S(2)P(3)T(4)S(5)P(6)S(7). While these repeats are critical for viability,
      they are not required for basal transcriptional activity in vitro. This suggests
      that - even though the CTD is not catalytically essential - it must perform other
      critical functions in eukaryotes. PRESENTATION OF THE HYPOTHESIS: By formally
      applying the long-standing mathematical principles of information theory, I
      explore the hypothesis that complex post-translational modifications of the CTD
      represent a means for the dynamic "programming" of Rpb1p and thus for the
      discrete modulation of the expression of specific gene subsets in eukaryotes.
      TESTING THE HYPOTHESIS: Empirical means for testing the informational capacity
      and regulatory potential of the CTD - based on simple genetic analysis in yeast
      model systems - are put forward and discussed. IMPLICATIONS OF THE HYPOTHESIS:
      These ideas imply that the controlled manipulation of CTD effectors could be used
      to "program" the CTD and thus to manipulate biological processes in eukaryotes in
      a definable manner.

PMID- 22591783
TI  - Technique and results of endoscopic tenotomy in iliopsoas muscle tendinopathy
      secondary to total hip replacement: a series of 10 cases.
AB  - INTRODUCTION: There have been numerous recommendations for management of
      iliopsoas tendinopathy secondary to hip replacement: medical treatment, cup
      replacement, and open or arthroscopic tenotomy. MATERIAL AND METHOD: We report on
      a series of 10 endoscopic iliopsoas tenotomies. Arthroplasty comprised five
      primary conventional total prostheses, two large head diameter metal-metal
      models, one resurfacing and one revision arthroplasty. All patients underwent
      clinical (PMA, WOMAC), imaging (X-ray, CT, scintigraphy) and biological
      assessment. Seven cases showed mechanical impingement (six involving the anterior
      edge of the cup, and one a cement fragment); the other three involved large
      femoral components (two large head diameter models, one resurfacing).
      Infiltration test was positive in eight cases out of nine. Endoscopic iliopsoas
      tenotomy for recurrence was performed in dorsal decubitus on an ordinary table,
      under fluoroscopy, using two approaches (inferior for the endoscope, superior for
      the instruments) converging on the lesser trochanter. DISCUSSION: There were no
      complications. At a mean 20 months' follow-up (range, 12-60 months), mean pain
      grade was 5.5 (4-6). Eight patients showed complete relief, and two partial
      relief (two atypical cases). Mean PMA score was 16.9 (15-18) and mean WOMAC score
      84 (60-95). Muscle force was recovered at a mean 3.25 months (0.5-6). Eight
      patients were very satisfied, one satisfied and one moderately satisfied.
      CONCLUSION: This technique is much less heavy than implant replacement;
      postoperative course is shorter than for open tenotomy and the technique is
      simpler than arthroscopic tenotomy, with lower risk. Subsequent cup change, where
      necessary, is not compromised. LEVEL OF EVIDENCE: IV, retrospective, case series.

PMID- 22591784
TI  - Cervical myelopathy due to ossification of the transverse atlantal ligament: a
      Caucasian case report operated on and literature analysis.
AB  - One case of cervical myelopathy associated to ossification of transverse atlantal
      ligament (OTAL) and C1 posterior arch hypoplasia in a Caucasian adult female is
      reported. A 53-year-old female affected by cervical myelopathy was treated with
      C1 laminectomy and posterior arthrodesis. CT scan demonstrated that the distance
      between ossification of the ligament and anterior cortex of the posterior arch of
      atlas was 6,2mm leading to consistent space reduction for spinal cord at this
      level. Patient underwent spinal cord decompression and fixation with C1 poliaxial
      screws in lateral masses and two bilateral crossing C2 laminar screws with an
      improvement of neurological functions at 4-years follow-up. The association
      between OTAL and C1 hypoplasia was reported in very few cases. The treatment with
      C1 laminectomy without fusion is reported in medical literature with good
      clinical outcome. Our patient obtained a neurological improvement at midterm
      follow-up with spinal cord decompression and fusion.

PMID- 22591785
TI  - Idiopathic club foot treated with the Ponseti method. Clinical and sonographic
      evaluation of Achilles tendon tenotomy. A review of 221 club feet.
AB  - The Ponseti method applied to treating idiopathic club foot consists in placing
      successive corrective casts, possibly an Achilles tendon tenotomy, then
      derotation braces, a method that has proven its efficacy. This study compared 221
      cases of club foot treated with this method between 2002 and 2007 divided into
      two groups, based on whether or not Achilles tendon tenotomy was performed.
      Assessment was both clinical and sonographic. We observed clear improvement of
      the results in the group that underwent Achilles tendon tenotomy and a
      significant difference in the rate of secondary surgery. The sonographic
      evaluation also showed improvement of the morphological results. We now
      systematically propose Achilles tendon tenotomy however severe club foot may be.

PMID- 22591786
TI  - Effect of age and severity of cognitive dysfunction on spontaneous activity in
      pet dogs - part 1: locomotor and exploratory behaviour.
AB  - Age-related cognitive dysfunction syndrome (CDS) has been reported in dogs and it
      is considered a natural model for Alzheimer's disease in humans. Changes in
      spontaneous activity (including locomotor and exploratory behaviour) and social
      responsiveness have been related to the age and cognitive status of kennel-reared
      Beagle dogs. The aim of this study was to assess the influence of age and
      severity of CDS on locomotor and exploratory behaviour of privately owned dogs.
      This is the first part of a two-part report on spontaneous activity in pet dogs.
      An open-field (OF) test and a curiosity test were administered at baseline and 6
      months later to young (1-4 years, n=9), middle-aged (5-8 years, n=9), cognitively
      unimpaired aged (>= 9 years, n=31), and cognitively impaired aged ( >= 9 years,
      n=36) animals. Classification of cognitive status was carried out using an owner
      based observational questionnaire, and in the cognitively impaired group, the
      dogs were categorised as having either mild or severe cognitive impairment. Dogs
      were recorded during sessions in the testing room and the video-recordings were
      subsequently analysed. The severity of CDS (but not age) influenced locomotion
      and exploratory behaviour so that the more severe the impairment, the higher the
      locomotor activity and frequency of corner-directed (aimless) behaviours, and the
      lower the frequency of door-aimed activities. Curiosity directed toward novel
      stimuli exhibited an age-dependent decline although severely affected animals
      displayed more sniffing episodes directed towards the objects. OF activity did
      not change after 6 months. Testing aged pet dogs for spontaneous behaviour might
      help to better characterise cognitively affected individuals.

PMID- 22591787
TI  - Long-term persistence of various 14C-labeled pesticides in soils.
AB  - The fate of the 14C-labeled herbicides ethidimuron (ETD), methabenzthiazuron
      (MBT), and the fungicide anilazine (ANI) in soils was evaluated after long-term
      aging (9-17 years) in field based lysimeters subject to crop rotation. Analysis
      of residual 14C activity in the soils revealed 19% (ETD soil; 0-10 cm depth), 35%
      (MBT soil; 0-30), and 43% (ANI soil; 0-30) of the total initially applied.
      Accelerated solvent extraction yielded 90% (ETD soil), 26% (MBT soil), and 41%
      (ANI soil) of residual pesticide 14C activity in the samples. LC-MS/MS analysis
      revealed the parent compounds ETD and MBT, accounting for 3% and 2% of applied
      active ingredient in the soil layer, as well as dihydroxy-anilazine as the
      primary ANI metabolite. The results for ETD and MBT were matching with values
      obtained from samples of a 12 year old field plot experiment. The data
      demonstrate the long-term persistence of these pesticides in soils based on
      outdoor trials.

PMID- 22591788
TI  - Environmental risks of trace elements associated with long-term phosphate
      fertilizers applications: a review.
AB  - Application of phosphate fertilizer can be a significant contributor of
      potentially hazardous trace elements such as arsenic, cadmium, and lead in
      croplands. These trace elements have the potential to accumulate in soils and be
      transferred through the food chain. We articulated the environmental risks of
      trace elements associated with long-term phosphate fertilizer applications by
      combining data from the literature and results from model simulations. Results
      illustrate that under normal cropping practice, the impact of phosphate
      fertilizers applications on trace element accumulation in receiving soils has
      been limited and localized. Their plant uptake varied greatly depending on the
      fertilizer application rates, soil and plant characteristics. This has led to a
      great deal of uncertainty in characterizing soil distribution coefficients, Kd,
      and plant uptake factors, PUF, two of the most used parameters in assessing the
      risks of accumulations. Therefore, the risks may be more appropriately assessed
      based on the probabilistic distributions of Kd and PUF.

PMID- 22591789
TI  - Evaluation of acute toxicity and teratogenic effects of disinfectants by Daphnia
      magna embryo assay.
AB  - Three common disinfectants were selected in this study to investigate their
      toxicity to Daphnia magna. The methods used in this study included the
      traditional acute toxicity test, new embryo toxicity test, and teratogenic test.
      The study concluded that the acute toxicity of the three disinfectants to young
      daphnids and embryos were hypochlorite > formaldehyde > m-cresol. The effects on
      growth mostly occurred in the late stages of organogenesis. Of the organs, the
      Malpighian tube was the most sensitive to disinfectants during embryonic
      organogenesis. After exposure of the disinfectants to sunlight for 4 h, acute
      toxicity and teratogenic effects of hypochlorite on young daphnids decreased by
      30% and 71%, respectively, while those of formaldehyde decreased by 35% and 49%,
      respectively. In addition, comparing toxic endpoints of the three disinfectants
      with and without sunlight exposure, the embryo tests were equally sensitive to
      the three-week reproduction test in this study.

PMID- 22591790
TI  - Gender differences in trunk, pelvis and lower limb kinematics during a single leg
      squat.
AB  - The relationship between trunk and lower limb kinematics in healthy females
      versus males is unclear since trunk kinematics in the frontal and transverse
      planes have not been systematically examined with lower limb kinematics. The aim
      of this study was to investigate the existence of different multi-joints movement
      strategies between genders during a single leg squat. We expected that compared
      to males, females would have greater trunk and pelvis displacement due to less
      trunk control and display hip and knee movement consistent with medial-collapse
      (i.e. greater hip adduction, hip medial rotation, knee abduction, and knee
      lateral rotation) on the weight-bearing limb. Nine females and 10 males
      participated in the study. Kinematic data were collected using an 8-camera, 3D
      motion-capture-system. Trunk relative to pelvis, pelvis relative to the
      laboratory, hip and knee angles in three planes (sagittal, frontal and
      transverse) were examined at two time events relevant to knee joint mechanics: 45
      degrees  of knee flexion and peak knee flexion. Females flexed their trunk less
      than males and rotated their trunk and pelvis toward the weight-bearing limb more
      than males. Females also displayed greater hip adduction and knee abduction than
      males. Taken together these results suggest that females and males used different
      movement strategies during a single leg squat. Females displayed a trunk and
      pelvic movement pattern that may put them at risk of knee injury and pain.

PMID- 22591791
TI  - Foot kinematics and loading of professional athletes in American football
      specific tasks.
AB  - The purpose of this study was to describe stance foot and ankle kinematics and
      the associated ground reaction forces at the upper end of human performance in
      professional football players during commonly performed football-specific tasks.
      Nine participants were recruited from the spring training squad of a professional
      football team. In a motion analysis laboratory setting, participants performed
      three activities used at the NFL Scouting Combine to assess player speed and
      agility: the 3-cone drill, the shuttle run, and the standing high jump. The
      talocrural and first metatarsophalangial joint dorsiflexion, subtalar joint
      inversion, and the ground reaction forces were determined for the load bearing
      portions of each activity. We documented load-bearing foot and ankle kinematics
      of elite football players performing competition-simulating activities, and
      confirmed our hypothesis that the talocrural, subtalar, and metatarsophalangeal
      joint ranges of motion for the activities studied approached or exceeded reported
      physiological limits. 

PMID- 22591792
TI  - Repeatability of a 3D multi-segment foot model protocol in presence of foot
      deformities.
AB  - Repeatability studies on 3D multi-segment foot models (3DMFMs) have mainly
      considered healthy participants which contrasts with the widespread application
      of these models to evaluate foot pathologies. The current study aimed at
      establishing the repeatability of the 3DMFM described by Leardini et al. in
      presence of foot deformities. Foot kinematics of eight adult participants were
      analyzed using a repeated-measures design including two therapists with different
      levels of experience. The inter-trial variability was higher compared to the
      kinematics of healthy subjects. Consideration of relative angles resulted in the
      lowest inter-session variability. The absolute 3D rotations between the Sha-Cal
      and Cal-Met seem to have the lowest variability in both therapists. A general
      trend towards higher sigma(sess)/sigma(trial) ratios was observed when the
      midfoot was involved. The current study indicates that not only relative 3D
      rotations and planar angles can be measured consistently in patients, also a
      number of absolute parameters can be consistently measured serving as basis for
      the decision making process.

PMID- 22591793
TI  - Sustained activation of microglia in the hypothalamic PVN following myocardial
      infarction.
AB  - Microglia are the immune cells in the central nervous system and can produce
      cytokines when they are activated by an insult or injury. In the present study,
      we investigated in detail the time frame of the activation of microglia in the
      hypothalamic paraventricular nucleus (PVN) following myocardial infarction in
      rats. Morphological changes and immunohistochemistry to detect CD11b (clone OX
      42) were used to identify activated microglia. Compared to rats that had
      undergone sham surgical procedures, there was a significant increase of between
      40 and 50% in the proportion of activated microglia in the PVN 4-16 weeks
      following myocardial infarction (P<0.001, One way ANOVA). At 24h or 1 week post
      myocardial infarction, however, there was no significant increase in the
      proportion of activated microglia. Echocardiography and haemodynamic parameters
      after myocardial infarction indicated significantly reduced left ventricular
      function. In conclusion, following myocardial infarction, activation of microglia
      in the PVN does not occur immediately but once manifested, activation is
      sustained. Thus, activated microglia may contribute to the chronic elevation in
      cytokine levels observed following myocardial infarction. Since cytokines elicit
      sympatho-excitatory effects when locally microinjected into the PVN, activated
      microglia may contribute to the mechanisms mediating the chronic increase in
      sympathetic nerve activity in animals with reduced left ventricular function
      induced following myocardial infarction.

PMID- 22591794
TI  - Survey of conformational isomerism in (E)-2-[(4-bromophenylimino)methyl]-5
      (diethylamino)phenol compound from structural and thermochemical points of view.
AB  - In this study, (E)-2-[(4-bromophenylimino)methyl]-5-(diethylamino)phenol compound
      was investigated by mainly focusing on conformational isomerism. For this
      purpose, molecular structure and spectroscopic properties of the compound were
      experimentally characterized by X-ray diffraction, FT-IR and UV-Vis spectroscopic
      techniques, and computationally by DFT method. The X-ray diffraction analysis of
      the compound shows the formation of two conformers (anti and eclipsed) related to
      the ethyl groups of the compound. The two conformers are connected to each other
      by non-covalent C-H?Br and C-H?pi interactions. The combination of these
      interactions is resulted in fused R(2)(2)(10) and R(2)(4)(20) synthons which are
      responsible for the tape structure of crystal packing arrangement. The X-ray
      diffraction and FT-IR analyses also reveal the existence of enol form in the
      solid state. From thermochemical point of view, the computational investigation
      of isomerism includes three studies: the calculation of (a) the rate constants
      for transmission from anti or eclipsed conformations to transition state by using
      Eyring equation, (b) the activation energy needed for isomerism by using
      Arrhenius equation, (c) the equilibrium constant from anti conformer to eclipsed
      conformer by using the equation including the change in Gibbs free energy. The
      dependence of tautomerism on solvent types was studied on the basis of UV-Vis
      spectra recorded in different organic solvents. The results showed that the
      compound exists in enol form in all solvents except ethyl alcohol.

PMID- 22591795
TI  - Spectral characteristics of 4-(p-N,N-dimethyl-aminophenylmethylene)-2-phenyl-5
      oxazolone (DPO) in different media.
AB  - The absorption and fluorescence characteristics of 4-(p-N,N-dimethyl
      aminophenylmethylene)-2-phenyl-5-oxazolone (DPO) have been investigated in
      different solvents. DPO dye exhibits a large red shift in both absorption and
      emission spectra as solvent polarity increases, indicating a large change in the
      dipole moment of dye molecules upon excitation due to an intramolecular charge
      transfer interaction. The fluorescence quantum yield depends strongly on the
      properties of the solvents. Crystalline solids of DPO gave strong red emission at
      605nm due to the excitation of molecular aggregates. The absorption and
      fluorescence emission spectral properties of DPO have also been investigated in
      organized media of aqueous micellar and beta-cyclodextrin (beta-CD) solutions.
      The critical micelle concentrations (CMCs) of SDS and CTAB as well as the binding
      constants of DPO in micellar solution and beta-cyclodextrin have been also
      determined.

PMID- 22591796
TI  - Spectrophotometric studies and applications for the determination of Ni2+ in zinc
      nickel alloy electrolyte.
AB  - The absorption properties of zinc-nickel alloy electrolyte were studied by
      visible spectrophotometer. The results show that the relationship between the
      absorbance of the zinc-nickel alloy electrolyte and Ni(2+) concentration in the
      electrolyte obeys Beer's law at 660 nm. In addition, other components except
      Ni(2+) in the zinc-nickel alloy electrolyte such as zinc chloride, ammonium
      chloride, potassium chloride and boric acid have no obvious effect on the
      absorbance of zinc-nickel alloy electrolyte. Based on these properties, a new
      method is developed to determine Ni(2+) concentration in zinc-nickel alloy
      electrolyte. Comparing with other methods, this method is simple, direct and
      accurate. Moreover, the whole testing process does not consume any reagent and
      dilution, and after testing, the electrolyte samples can be reused without any
      pollution to the environment.

PMID- 22591797
TI  - Microplate assay for screening the antibacterial activity of Schiff bases derived
      from substituted benzopyran-4-one.
AB  - Schiff bases (SB(1)-SB(3)) were synthesized from the condensation of 6-formyl-7
      hydroxy-5-methoxy-2-methylbenzopyran-4-one with 2-aminopyridine (SB(1)), p
      phenylenediamine (SB(2)) and o-phenylenediamine (SB(3)), while Schiff bases
      (SB(4)-SB(6)) were synthesized by condensation of 5,7-dihydroxy-6-formyl-2
      methylbenzopyran-4-one with 2-aminopyridine (SB(4)), p-phenylenediamine (SB(5))
      and o-phenylenediamine (SB(6)). Schiff bases were characterized using elemental
      analysis, IR, UV-Vis, (1)H NMR, (13)C NMR and mass spectroscopy. These compounds
      were screened for antibacterial activities by micro-plate assay technique.
      Escherichia coli and Staphylococcus capitis were exposed to different
      concentrations of the Schiff bases. Results showed that the antibacterial effect
      of these Schiff bases on Gram-negative bacteria were higher than that on Gram
      positive bacteria moreover, the Schiff bases containing substituent OCH(3) on
      position five have higher antibacterial activity than that containing hydroxy
      group on the same position.

PMID- 22591798
TI  - Determination of lapachol in the presence of other naphthoquinones using 3MPA
      CdTe quantum dots fluorescent probe.
AB  - 3MPA-CdTe QDs in aqueous dispersion was used as a fluorescent probe for the
      determination of lapachol, a natural naphthoquinone found in plants of the
      Bignoniaceae family genus Tabebuia. Working QDs dispersions (4.5*10(-8) mol L(-1)
      of QDs) was prepared in aqueous media containing Tris-HCl buffer pH 7.4 and
      methanol (10% in volume). The excitation was made at 380 nm with signal
      measurement at 540 nm. To establish a relationship between fluorescence
      (corrected to inner filter effect) and concentration of lapachol, a Stern-Volmer
      model was used. The linear range obtained was from 1.0*10(-5) to 1.0*10(-4) mol
      L(-1). The limit of detection (x(b)-3s(b)) was 8.0*10(-6) mol L(-1). The 3MPA
      CdTe QDs probe was tested in the determination of lapachol in urine, previously
      cleansed in an acrylic polymer. The average recovery was satisfactory.

PMID- 22591799
TI  - Spectrofluorimetric determination of tetrabenazine after photochemical
      derivatization in basic medium.
AB  - Photochemical derivatization is proposed for the spectrofluorimetric
      determination of tetrabenazine (TBZ). A central composite design was used to
      adjust experimental conditions (60 min of UV in a 0.45 mol L(-1) NaOH solution)
      enabling the improvement of the analyte signal-to-blank ratio of one order of
      magnitude, when compared to the TBZ original fluorescence. Limit of
      quantification was 4.7*10(-8) mol L(-1) but the detection power can be improved
      at least 10 times using solid phase extraction that also allows the separation of
      the analyte from matrix components, enabling the analysis of biologic fluids.
      Linear range covered at least three orders of magnitude. The combined uncertainty
      of the determination (at a 5*10(-6) mol L(-1)) was 16%. Recoveries of TBZ in the
      analyses of a pharmaceutical formulation were in agreement with the ones obtained
      using a HPLC method. Recovery in saliva (5*10(-7) mol L(-1) of TBZ) was 90+/-3%
      (n=3). The procedure minimizes the use of toxic chemical derivatization reagents
      and the generation of hazardous waste.

PMID- 22591800
TI  - DFT based ESIPT process of luminescent chemosensor: Taft and Catalan
      solvatochromism.
AB  - Amino acid containing o-hydroxy Schiff base derivative was synthesized and an
      excited state intramolecular proton transfer (ESIPT) process in o-hydroxy Schiff
      base (HBMBA) has been studied using solution spectral studies. It was detected
      that the two distinct ground state isomers I and II are responsible for the
      emission. By comparing the emission wavelength in hydrocarbon solvent, it was
      predicted that the trans enol form predominates over the cis enol form. DFT
      calculations on energy, dipole moment, charge distribution of the rotamers in the
      ground and excited states of the Schiff base derivative were performed and
      discussed. PES calculation indicates that the energy barrier for the
      interconversion of two rotamers is too high in the excited state than in the
      ground state. The fluorescence of HBMBA quenched with the gradual addition of
      Cu(2+). Therefore the prepared Schiff base HBMBA can be used as a new fluorescent
      sensor to detect the quantity of Cu(2+) ions in any sample solution depending on
      the relative intensity change. Measurements of absorption solvatochromism have
      been interpreted with Marcus and Reichardt-Dimroth solvent functions to estimate
      the transition dipoles. Good correlation exists between absorption as well as
      fluorescence wavenumbers obtained by the multi-component linear regression
      employing the Taft and Catalan solvent parameters with the experimental values.

PMID- 22591801
TI  - The influence of preterm birth on structural alterations of the vision-deprived
      brain.
AB  - Differences in brain structures between blind and sighted individuals have not
      been widely investigated. Furthermore, existing studies have included individuals
      who were blinded by retinopathy of prematurity, a condition that is associated
      with premature birth. Recent pediatric research has reported structural
      differences in individuals who were born prematurely, suggesting that some of the
      structural abnormalities previously observed in blind individuals may be related
      to prematurity rather than being specific to blindness. In the present study, we
      used voxel-based morphometry to investigate gray and white matter differences
      between 24 blind and 16 sighted individuals. Of the blind individuals, six were
      born prematurely and 18 at term. Compared to those born at term, blind
      individuals born preterm showed differences in gray, but not white, matter
      volumes in various brain regions. When the preterm individuals were excluded from
      analysis, there were significant differences between blind and sighted
      individuals. Full-term blind individuals showed regional gray matter decreases in
      the cuneus, lingual gyrus, middle occipital gyrus, precuneus, inferior and
      superior parietal lobules, and the thalamus, and gray matter increases in the
      globus pallidus. They also showed regional white matter decreases in the cuneus,
      lingual gyrus, and the posterior cingulate. These differences were observed in
      blind individuals irrespective of blindness onset age, providing evidence for
      structural alterations in the mature brain. Our findings highlight the importance
      of considering the potential impact of premature birth on neurodevelopmental
      outcomes in studies of blind individuals.

PMID- 22591802
TI  - Involuntary movements after correction of vitamin B12 deficiency: a video-case
      report.
AB  - Involuntary movements can appear before and after initiation of vitamin B12
      treatment. The pathogenesis of involuntary movements in vitamin B12 deficiency
      and their relationship with cobalamin injection remain unclear due to a lack of
      video-EEG documentation making the electroclinical correlation difficult to
      ascertain. Here, we report video-EEG and neuroimaging findings of an 11-month-old
      girl with vitamin B12 deficiency, who acutely developed involuntary movements a
      few days after initiation of vitamin B12 treatment with normal vitamin plasmatic
      levels. Abnormal movements were a combination of tremor and myoclonus involving
      the face, mouth, and left arm, which disappeared after discontinuation of
      therapy. [Published with video sequences].

PMID- 22591803
TI  - Isolation and structure characterization of related impurities in Sodium
      Tanshinone IIA Sulfonate by LC/ESI-MS(n) and NMR.
AB  - Sodium Tanshinone IIA Sulfonate (STS) is a water-soluble derivative of tanshinone
      IIA, an important lipophilic component isolated from the roots of Salvia
      miltiorrhiza. STS, as injection drug, is widely and successfully used in China
      for treating cardiovascular disease. Eight impurities were detected in STS bulk
      drug by LC-UV and LC-ESI-MS(n). Low pressure C18 column chromatography and
      preparative HPLC were used for the isolation of three principal impurities. Based
      on LC/ESI-MS(n) and NMR analysis, related impurities were characterized as sodium
      (+/-)-hydroxyl tanshinone sulfonate (1), sodium tanshinone I sulfonate (2),
      sodium salvianolic acid sulfonate (3), sodium 1,2-dehydrotanshinone IIA sulfonate
      (4), sodium tanshinone IIB sulfonate (5), sodium 3-hydroxyl salvianolic acid
      sulfonate (6), sodium 1,16-dihydroxyl-15,16-dihydrotanshinone IIA sulfonate (7),
      and sodium methyl 1,2-dehydrotanshinonate sulfonate (8). The 1H and 13C NMR data
      of impurity 1 were reported in this paper for the first time. Also, to the best
      of our knowledge, impurity 4 had not been isolated as pure substance until now.
      The possible mechanism for the formation of impurities is also discussed.

PMID- 22591804
TI  - Identification of metabolites of Buyang Huanwu decoction in rat urine using
      liquid chromatography-quadrupole time-of-flight mass spectrometry.
AB  - In the present study, rapid resolution liquid chromatography was coupled with
      quadrupole time-of-flight tandem mass spectrometry (RRLC-Q-TOF-MS) to identify
      the absorbed components and metabolites in rat urine after oral administration of
      Buyang Huanwu decoction (BYHWD). After oral administration of BYHWD, urine
      samples were collected and pretreated by solid phase extraction. The mass
      measurements were accurate within 5 ppm of error for all the protonated
      molecules, and subsequent fragment ions offered higher quality structural
      information for interpretation of the fragmentation pathways of various
      compounds. A total of 50 compounds were detected in rat urine samples within 20
      min, including 12 parent compounds and 38 metabolites. Except for three prototype
      components (Hydroxysafflor yellow A, Paeoniflorin, and Amygdalin), the
      metabolites identified mainly came from Radix Astragali, Radix Angelicae
      Sinensis, and Rhizoma Chuanxiong. The results indicated that glucuronidation and
      sulfation were the major metabolic pathways of isoflavonoids, while glutathione
      conjugation, glucuronidation and sulfation were the main metabolic pathways of
      phthalides. No saponin-related metabolites were detected. The present study
      provided important structural information on the metabolism of BYHWD.
      Furthermore, the results of this work have demonstrated the feasibility of the
      RRLC/ESI-Q-TOF-MS approach for rapid and reliable characterization of metabolites
      from herbal medicines.

PMID- 22591805
TI  - Characterization of currently marketed heparin products: adverse event relevant
      bioassays.
AB  - The polyanion oversulfated chondroitin sulfate (OSCS) was identified as a
      contaminant in heparin products and was associated with severe hypotensive
      responses and other symptoms in patients receiving the drug. The OSCS associated
      adverse reactions were attributed to activation of the contact system via the
      plasma mediator, activated factor XII (FXIIa), which triggers kallikrein (KK)
      activity. Unlike heparin alone, OSCS, is able to activate FXII in plasma and
      stably bind to FXIIa enhancing plasma KK activity and the induction of vasoactive
      mediators such as bradykinin (BK), C3a and C5a. Similarly OSCS can interfere with
      heparin neutralization by the polycationic drug protamine. Here, we assess
      heparin (heparin sodium, dalteparin, tinzaparin or enoxaparin)-protamine complex
      formation and plasma based bioassays of KK, BK and C5a in a 96-well plate format.
      We establish the normal range of variation in the optimized bioassays across
      multiple lots from 9 manufacturers. In addition, because other oversulfated (OS)
      glycosaminoglycans (GAGs) besides OSCS could also serve as possible economically
      motivated adulterants (EMAs) to heparin, we characterize OS-dermatan sulfate
      (OSDS), OS-heparan sulfate (OSHS) and their native forms in the same assays. For
      the protamine test, OS-GAGs could be distinguished from heparin. For the KK
      assay, OSCS and OSDS were most potent followed by OSHS, and all had similar
      efficacies. Finally, OSDS had a greater efficacy in the C5a and BK assays
      followed by OSCS then OSHS. These data established the normal range of response
      of heparin products in these assays and the alteration in the responses in the
      presence of possible EMAs.

PMID- 22591806
TI  - Identification of crotonyl glycine in urine of sheep after 48 h road transport.
AB  - Thousands of metabolites are excreted in urine, and potentially can be detected
      in NMR spectra. Currently, NMR spectral information for about one thousand
      metabolites has been deposited in publicly available sources, limiting the
      identification of chemical compounds that are potential biomarkers for clinical
      and subclinical applications. This study reports the identification of crotonyl
      glycine, one of the key metabolites detected by 1H NMR as excreted in the urine
      of sheep after 48 h road transport and during the subsequent 72 h recovery
      period. This metabolite was important in separating the metabolic responses as
      expressed in the urine from animals undergoing shorter road transport treatments.
      At the time of the metabonomic analysis, the NMR signals from this metabolite
      were designated as unassigned as no match was found in public databases or the
      literature. Selected sheep urine samples containing the metabolite were resolved
      by reversed phase HPLC reducing the sample complexity. Subsequent 1H NMR spectra
      of the collected fractions revealed that the unknown metabolite was present in a
      single HPLC fraction. High-resolution 1D and 2D 1H NMR spectra of this fraction
      followed by mass determination of the parent ion and its fragments by nanoESI-TOF
      MS/MS revealed the identity of the compound as crotonyl glycine (N-but-(E)-2
      enoyl glycine). The HPLC fraction was subsequently spiked with synthetic crotonyl
      glycine which confirmed identification.

PMID- 22591807
TI  - Effects of interdot hopping and Coulomb blockade on the thermoelectric properties
      of serially coupled quantum dots.
AB  - : We have theoretically studied the thermoelectric properties of serially
      coupled quantum dots (SCQDs) embedded in an insulator connected to metallic
      electrodes. In the framework of Keldysh Green's function technique, the Landauer
      formula of transmission factor is obtained using the equation of motion method.
      Based on such analytical expressions of charge and heat currents, we calculate
      the electrical conductance, Seebeck coefficient, electron thermal conductance,
      and figure of merit (ZT) of SCQDs in the linear response regime. The effects of
      interdot hopping and electron Coulomb interactions on ZT are analyzed. We
      demonstrate that ZT is not a monotonic increasing function of interdot electron
      hopping strength (tc). We also show that in the absence of phonon thermal
      conductance, SCQD can reach the Carnot efficiency as tcapproaches zero.

PMID- 22591808
TI  - Kinetic stability of all-in-one parenteral nutrition admixtures in the presence
      of high dose Ca2+ additive under clinical application circumstances.
AB  - BACKGROUND: TPN infusions are usually administered during a treatment period of
      10-24 hours per day due to the metabolic capacity of the liver. During this time
      interval physicochemically stable TPN solution (emulsion) is needed for the
      treatment. The purpose of the present study was to examine how the kinetic
      stability features of ready-made total parenteral nutrition admixtures containing
      olive oil and soybean oil will change under the usage-modeling 24-hour
      application with and without overdose Ca2+. METHODS: Particle size analysis and
      zeta potential measurements were carried out to evaluate the possible changes in
      the kinetic stability of the emulsions. RESULTS: Our results indicate that in two
      of the four mixtures bimodal droplet-size distribution figures were detected and
      appearance of fat particles over 5 MUm can not be disclosed. The tendency for
      separation of large diameter droplets in the two types of oil-based emulsion
      systems was different. In case of soybean containing emulsion second peak of
      droplets appeared in the bottom of the container in contrast to the olive oil
      containing emulsions where the second peak appeared in the surface layer.
      Interestingly this phenomenon is independent of calcium-content. CONCLUSIONS:
      From therapeutic point the emulsions of the bigger droplets containing upper
      layer are safer because the potentially dangerous big droplets could remain in
      the infusion bag after the administration.

PMID- 22591809
TI  - Paroxysmal tonic upgaze in normal children: a case series and a review of the
      literature.
AB  - The purpose of this review was to update the clinical characteristics of
      paroxysmal tonic upgaze in neurodevelopmentally normal children. We made the
      diagnosis (between 2008 and 2010) in 8 infants referred to us with suspected
      epilepsy. We found 38 further cases in the literature. In the 46 children (29
      boys and 17 girls) tonic upward ocular deviation was first noticed between the
      age of 2 weeks and 90 months (median: 9 months). This tendency persisted for
      between 1 and 48 months (median: 7 months). The duration of paroxysmal events was
      highly variable: brief events lasted between 3 s and 10 min in 50% of the cases,
      intermediate events between 5 s and 30 min and long events between 10 s and 2 h.
      The frequency ranged from one every 3 months to 10 per day. In 15 children the
      episodes of upward deviation of the eyes were associated with an impaired
      movement coordination. In 2 further children an impaired movement coordination
      was noted during febrile illnesses. The results of this review in normal children
      characterize the entity as follows: onset under 2 years of age, a small
      predilection for the male gender, eventual improvement and recovery, and impaired
      movement coordination.

PMID- 22591810
TI  - Timing of external ventricular drainage and neurodevelopmental outcome in preterm
      infants with posthemorrhagic hydrocephalus.
AB  - OBJECTIVE: To delineate the impact of early (<= 25 days of life) versus late (>
      25 days) external ventricular drainage (EVD) on the neurodevelopmental outcome of
      preterm infants with posthemorrhagic hydrocephalus (PHH) following
      intraventricular hemorrhage (IVH). METHODS: We retrospectively categorized 32
      premature infants with PHH into two groups according to whether they underwent
      early (n = 10) or late (n = 22) EVD. We administered the Battelle Developmental
      Inventory II and a neuromotor examination (median age, 73 months, range: 29-100).
      RESULTS: In adjusted comparisons, early EVD was associated with better scores
      than late EVD in adaptive (79 +/- 22.6 vs. 58.8 +/- 8.1, P = .01), personal
      social (90.7 +/- 26 vs. 67.3 +/- 15.9, P = .02), communication (95.4 +/- 27.5 vs.
      69.6 +/- 20.5, P = .04) and cognitive (78.9 +/- 24.4 vs. 60.7 +/- 11.5, P = .055)
      functions. Three (30%) early EVD infants had severe (<2.5 standard deviation)
      cognitive disability compared to 18 (82%) late EVD infants (P = .03). The
      incidences of cerebral palsy and neurosurgical complications were equal for the
      two groups. Subgroup analyses suggested that early EVD was beneficial in infants
      with original grade III IVH (n = 15, P < 0.05), but that it had no beneficial
      effects in infants with prior parenchymal injury (n = 17, P = NS). CONCLUSION: In
      this small retrospective series, early EVD is associated with lower rates of
      cognitive, communication and social disabilities than later EVD in infants with
      PHH without prior parenchymal injury. A randomized prospective trial is
      warranted.

PMID- 22591811
TI  - Youth work service providers' attitudes towards computerized CBT for adolescents.
AB  - BACKGROUND: Attitudes of social service providers towards computerized CBT (cCBT)
      might affect use of cCBT by their clients and may provide important insights that
      should be considered in dissemination. There is no literature exploring the
      attitudes of providers of youth work services towards cCBT despite the likelihood
      of them having close relationships with young people at high risk of mental ill
      health. METHOD: Focus groups and semi-structured interviews were undertaken with
      a total of 40 providers (21 youth workers and social service staff providing
      alternative schooling, justice or other intensive youth work programmes to
      adolescents, 6 youth service managers, 2 trainers, 5 peer leaders and 6
      trainees). RESULTS: Participants considered supporting young people who were
      distressed to be an important part of their role. They were generally interested
      in cCBT, especially those who were more mental health oriented and those who saw
      a cCBT programme in action. Their greatest concerns regarding cCBT related to it
      possibly displacing human contact, while advantages were seen as its appeal to
      young people and its potential therapeutic power. They would utilize cCBT in a
      range of ways, with many wishing to offer it in group settings. Training and
      resources would be required for them to use cCBT. CONCLUSIONS: Many providers of
      youth work services would like to be involved in the use of cCBT; this might
      extend the reach of cCBT to vulnerable young people. They would wish to utilize
      cCBT in ways that fit their current approaches. Providers' opinions need to be
      considered in the dissemination of cCBT.

PMID- 22591812
TI  - On relative frequency estimation of transcranial magnetic stimulation motor
      threshold.

PMID- 22591813
TI  - Patients' perspectives on quality of mental health care for people with MS.
AB  - OBJECTIVE: The objective was to obtain multiple sclerosis (MS) patients' report
      on their experience receiving mental health care. METHODS: We convened focus
      groups at four MS clinical care centers to identify the aspects of mental health
      care that were important to people with MS. All patients (n=54) had received
      mental health care in the past year. Data were analyzed by coding comments under
      specific themes. RESULTS: Patients wanted prompt intervention after diagnosis and
      ongoing screening for mental health problems; they prefer providers with
      knowledge about MS and experience working with people with MS; they appreciated
      being able to access mental health services that were on-site at their MS center
      and noted the benefit of inclusion of family members in treatment. CONCLUSIONS:
      Mental health care should be provided promptly after diagnosis, with regular
      screening and interventions that include family members as indicated thereafter.
      Mental health providers should be familiar with MS, collaborate with neurologic
      care providers and provide services on-site at MS centers.

PMID- 22591814
TI  - The lipid profiles in Japanese patients with schizophrenia treated with
      antipsychotic agents.
AB  - OBJECTIVE: Antipsychotic-treated schizophrenia patients are susceptible to
      dyslipidemia. However, the results of previous studies of North American and UK
      populations including various races have been contradictory with regard to which
      lipid measure was the most affected in patients with schizophrenia taking
      antipsychotic agents. The aim of this study was to investigate the effect of
      schizophrenia patients receiving antipsychotic agents on each lipid measure in a
      Japanese population. METHODS: The samples included 136 control individuals and
      157 patients with schizophrenia treated with antipsychotic agents. Age, gender
      distribution and body mass index (BMI) of the controls were matched with the
      patients. RESULTS: The high-density lipoprotein cholesterol (HDL-cholesterol)
      levels were significantly lower in patients than in the control subjects
      (P<.001). However, there were no significant differences in either the low
      density lipoprotein cholesterol (LDL-cholesterol) or triglyceride levels between
      the patient and control groups. We performed a multiple linear regression
      analysis, and schizophrenia receiving antipsychotics was an independent predictor
      of decreased HDL-cholesterol. An increased BMI, male gender and cigarette smoking
      were also major predictors of a decreased HDL-cholesterol level (r(2)=0.42,
      P<.001). CONCLUSION: At least in Japanese with schizophrenia receiving
      antipsychotic agents, the HDL-cholesterol levels should be closely monitored in
      all patients, even those who are not obese or do not smoke, to decrease their
      risk of cardiovascular disease.

PMID- 22591815
TI  - A group of atopic dermatitis without IgE elevation or barrier impairment shows a
      high Th1 frequency: possible immunological state of the intrinsic type.
AB  - BACKGROUND: Atopic dermatitis (AD) can be classified into the major extrinsic
      type with high serum IgE levels and impaired barrier, and the minor intrinsic
      type with normal IgE levels and unimpaired barrier. OBJECTIVE: To characterize
      the intrinsic type of Japanese AD patients in the T helper cell polarization in
      relation to the barrier condition. METHODS: Enrolled in this study were 21 AD
      patients with IgE<200kU/L (IgE-low group; 82.5+/-59.6kU/L) having unimpaired
      barrier, and 48 AD patients with IgE>500kU/L (IgE-high group; 8.050+/
      10.400kU/L). We investigated filaggrin gene (FLG) mutations evaluated in the
      eight loci common to Japanese patients, circulating Th1, Th2 and Th17 cells by
      intracellular cytokine staining and flow cytometry, and blood levels of
      CCL17/TARC, IL-18, and substance P by ELISA. RESULTS: The incidence of FLG
      mutations was significantly lower in the IgE-low group (10.5%) than the IgE-high
      group (44.4%) (normal individuals, 3.7%). The percentage of IFN-gamma-producing
      Th1, but not Th2 or Th17, was significantly higher in the IgE-low than IgE-high
      group. Accordingly, Th2-attracting chemokine CCL17/TARC, was significantly lower
      in the IgE-low than the IgE-high group. There were no differences between them in
      serum IL-18 levels, or the plasma substance P levels or its correlation with
      pruritus. CONCLUSION: The IgE-low group differed from the IgE-high group in that
      it had much less FLG mutations, increased frequency of Th1 cells, and lower
      levels of CCL17. In the intrinsic type, non-protein antigens capable of
      penetrating the unimpaired barrier may induce a Th1 eczematous response.

PMID- 22591816
TI  - Steroids in a typical swine farm and their release into the environment.
AB  - The occurrence and fate of fourteen androgens, four estrogens, five
      glucocorticoids and five progestagens were investigated by rapid resolution
      liquid chromatography-tandem mass spectrometry (RRLC-MS/MS) in a typical swine
      farm with lagoon waste disposal systems, in south China. Nineteen, 22 and 8 of 28
      steroids were detected at concentrations ranging from 2.2 +/- 0.1 ng/g (androsta
      1,4-diene-3,17-dione) to 14,400 +/- 394 ng/g (progesterone) in the feces samples,
      from 6.1 +/- 2.3 ng/L (17beta-boldenone) to 10,800 +/- 3190 ng/L (norgestrel) in
      the flush water samples, and from 5.0 +/- 0.2 ng/g (progesterone) to 225 +/- 79.4
      ng/g (5alpha-dihydrotestosterone) in the suspended particles, respectively. By
      comparing the types and concentrations of steroids in different treatment stages
      of the lagoon systems, it demonstrated that the lagoon systems used in the farm
      were not effective method to reduce various steroids in wastewater. Among the
      thirteen synthetic steroids detected in the swine feces and flush water, only
      seven (methyl testosterone, 17alpha-trenbolone, 17beta-trenbolone, 17alpha
      ethynyl estradiol, dexamethasone, medroxyprogesterone, and norgestrel) were
      regarded as the parent/metabolite compounds of animal exogenous usage. According
      to the estimated masses of steroids from feces and flush water, the excretion of
      steroids for sows were mainly from feces, but for piglets or barrows, most
      excreted steroids were through flush water rather than feces. The total daily
      excreted masses of androgens, estrogens, glucocortcoids and progestagens in the
      sow feces were in the range of 90.7-6310 MUg/d, which were up to a thousand fold
      of those in the feces of other growth stages indicating that the proportion of
      sow number in the swine farm directly influenced the total excretion mass of
      steroids. In addition, two natural steroids 4-androstene-3,17-dione and
      progesterone were worth notice due to their relatively high concentrations per
      sow excretion, 277 MUg/d and 6380 MUg/d, respectively, which are approximately
      equivalent to the daily excretion of 100 persons. Some steroids were also
      detected in the well water, vegetable field and receiving stream, and may pose
      potential high risks to some sensitive organisms in the receiving environment.

PMID- 22591817
TI  - Storage temperature affects distribution of carbon, VFA, ammonia, phosphorus,
      copper and zinc in raw pig slurry and its separated liquid fraction.
AB  - Chemical-mechanical separation of pig slurry into a solid fraction rich in dry
      matter, P, Cu and Zn and a liquid fraction rich in inorganic N but poor in dry
      matter may allow farmers to manage surplus slurry by exporting the solid fraction
      to regions with no nutrient surplus. Pig slurry can be applied to arable land
      only in certain periods during the year, so it is commonly stored prior to field
      application. This study investigated the effect of storage duration and
      temperature on chemical characteristics and P, Cu and Zn distribution between
      particle size classes of raw slurry and its liquid separation fraction. Dry
      matter, VFA, total N and ammonium content of both slurry products decreased
      during storage and were affected by temperature, showing higher losses at higher
      storage temperatures. In both products, total P, Cu and Zn concentrations were
      not significantly affected by storage duration or temperature. Particle size
      distribution was affected by slurry separation, storage duration and temperature.
      In raw slurry, particles larger than 1 mm decreased, whereas particles 250 MUm-1
      mm increased. The liquid fraction produced was free of particles >500 MUm, with
      the highest proportions of P, Cu and Zn in the smallest particle size class (<25
      MUm). The proportion of particles <25 MUm increased when the liquid fraction was
      stored at 5  degrees C, but decreased at 25  degrees C. Regardless of
      temperature, distribution of P, Cu and Zn over particle size classes followed a
      similar pattern to dry matter.

PMID- 22591818
TI  - Resuspension and settling of helminth eggs in water: Interactions with cohesive
      sediments.
AB  - Helminth parasite eggs in low quality water represent main food safety and health
      hazards and are therefore important indicators used to determine whether such
      water can be used for irrigation. Through sedimentation helminth eggs accumulate
      in the sediment, however resuspension of deposited helminth eggs will lead to
      increased concentration of suspended eggs in the water. Our study aimed to
      determine the erodibility (erosion rate and erosion threshold) and settling
      velocity of Ascaris and Trichuris eggs as well as cohesive sediment at different
      time points after incorporation into the sediment. Cohesive sediment collected
      from a freshwater stream was used to prepare a sediment bed onto which helminth
      eggs were allowed to settle. The erodibility of both sediment and helminth eggs
      was found to decrease over time indicating that the eggs were incorporated into
      the surface material of the bed and that this material was stabilized through
      time. This interaction between eggs and bulk sediment was further manifested in
      an increased settling velocity of suspended eggs when sediment was present in the
      suspension as compared to a situation with settling in clean water. The
      incorporation into the sediment bed and the aggregation with sediment particles
      decrease the mobility of both helminth egg types. Our findings document that
      helminth eggs should not be viewed as single entities in water systems when
      modelling the distribution of eggs since both erodibility and settling velocity
      of eggs are determined by mobility of the sediment present in the water stream.
      Recalculation of the erosion threshold for helminth eggs and sediment showed that
      even at relatively low current velocities i.e. 0.07-0.12ms(-1) newly deposited
      eggs will be mobile in open irrigation channels. These environmental factors
      affecting resuspension must be taken into account when developing models for
      sedimentation of helminth eggs in different water systems.

PMID- 22591819
TI  - Simultaneous nitrogen and phosphate removal in aerobic granular sludge reactors
      operated at different temperatures.
AB  - The main biological conversions taking place in two lab-scale aerobic granular
      sludge sequencing batch reactors were evaluated. Reactors were operated at
      different temperatures (20 and 30  degrees C) and accomplished simultaneous COD,
      nitrogen and phosphate removal. Nitrogen and phosphate conversions were linked to
      the microbial community structure as assessed by fluorescent in situ
      hybridization (FISH) analysis. Anoxic tests were performed to evaluate the
      contribution of anoxic phosphate uptake to the overall phosphate removal and to
      clarify the denitrification pathway. Complete nitrification/denitrification and
      phosphate removal were achieved in both systems. A considerable fraction of the
      phosphate removal was coupled to denitrification (denitrifying dephosphatation).
      From the results obtained in anoxic batch experiments dosing either nitrite or
      nitrate, denitrification was proposed to proceed mainly via the nitrate pathway.
      Denitrifying glycogen-accumulating organisms (DGAOs) were observed to be the main
      organisms responsible for the reduction of nitrate to nitrite. A significant
      fraction of the nitrite was further reduced to nitrogen gas while being used as
      electron acceptor by denitrifying polyphosphate-accumulating organisms (PAO clade
      II) for anoxic phosphate uptake.

PMID- 22591820
TI  - Carbo-Iron - An Fe/AC composite - As alternative to nano-iron for groundwater
      treatment.
AB  - Carbo-Iron((r))(1) is a novel colloidal composite consisting of activated carbon
      colloids (ACC) with a d(50) particle size of 0.8 MUm and anchored deposits of
      zero-valent iron clusters. This study discusses the principal material properties
      of Carbo-Iron colloids (CIC) relevant for groundwater treatment in comparison to
      commercially available nano-sized zero-valent iron (nZVI). CIC with 10-25 wt%
      Fe(0) have been developed and tested in laboratory studies for their suitability
      as dehalogenation reagent and are especially designed to overcome some
      limitations known from the utilization of nZVI: CIC combine the sorption
      properties of ACC and the chemical reactivity of nZVI. In column tests, flushed
      in CIC showed an enhanced mobility in sediment material compared to nZVI, without
      the need for colloid stabilizers. However, adding 1-3 wt-% of carboxymethyl
      cellulose (CMC) related to CIC as colloid stabilizer was found to assure long
      lived stable suspensions under laboratory conditions which may additionally
      support the already improved mobility of the CIC and the homogeneity of particle
      deposition on the sediment matrix. The hydrophobic character of the ACC carrier
      provides a high affinity of CIC to non-aqueous phase liquids (NAPL). In
      undisturbed flow, the reactive particles are collected at the water-NAPL
      interface. The reagent accumulation at the organic phase is necessary for a
      successful source attack.

PMID- 22591821
TI  - Evaluation of on-site biological treatment for landfill leachates and its impact:
      A size distribution study.
AB  - A cost effective and widely applied approach for landfill leachate disposal is to
      discharge it to a municipal wastewater treatment plant (WWTP). The recalcitrant
      nature of leachate organics and the impact on the downstream WWTPs were
      comprehensively investigated in this study. Size fractionation by ultrafiltration
      (UF) and microfiltration (MF) was employed in conjunction with various analyses
      (TOC, COD, nitrogen species and UV(254) absorbance) on raw and biologically
      treated landfill leachates to provide insight into biological treatability.
      Overall, landfill leachate organics showed bio-refractory properties. Less than
      half of the organic matter, measured as total organic carbon (TOC), could be
      removed in the biological processes examined. Size distribution data showed that
      the <1 thousand Daltons (kDa) fraction is dominant in most untreated and treated
      landfill leachates, indicating difficulties for membrane treatment. Also, most
      removal occurred for the <1 kDa fraction in the biological processes, while the
      intermediate size fractions increased slightly. This may be caused by bio
      flocculation and/or partial degradation of larger molecular weight fractions.
      Organic nitrogen was investigated in this study as one of the first explorations
      for landfill leachates. Organic nitrogen in landfill leachates was more bio
      refractory than other organic matter. UV quenching by landfill leachates was also
      investigated since it interferes with the UV disinfection at WWTPs. The
      combination of activated carbon and activated sludge (PACT) showed some
      effectiveness for reducing UV quenching, indicating that carbon adsorption is a
      potential method for removal of UV quenching substances. Fourier transform
      Infrared (FT/IR) data showed that aromatic groups are responsible for the UV
      quenching phenomenon.

PMID- 22591822
TI  - Ethnic density effects on health and experienced racism among Caribbean people in
      the US and England: a cross-national comparison.
AB  - Studies indicate an ethnic density effect, whereby an increase in the proportion
      of racial/ethnic minority people in an area is associated with reduced morbidity
      among its residents, though evidence is varied. Discrepancies may arise due to
      differences in the reasons for and periods of migration, and socioeconomic
      profiles of the racial/ethnic groups and the places where they live. It is
      important to increase our understanding of how these factors might promote or
      mitigate ethnic density effects. Cross-national comparative analyses might help
      in this respect, as they provide greater heterogeneity in historical and
      contemporary characteristics in the populations of interest, and it is when we
      consider this heterogeneity in the contexts of peoples' lives that we can more
      fully understand how social conditions and neighbourhood environments influence
      the health of migrant and racial/ethnic minority populations. This study analysed
      two cross-sectional nationally representative surveys, in the US and in England,
      to explore and contrast the association between two ethnic density measures
      (black and Caribbean ethnic density) and health and experienced racism among
      Caribbean people. Results of multilevel logistic regressions show that nominally
      similar measures of ethnic density perform differently across health outcomes and
      measures of experienced racism in the two countries. In the US, increased
      Caribbean ethnic density was associated with improved health and decreased
      experienced racism, but the opposite was observed in England. On the other hand,
      increased black ethnic density was associated with improved health and decreased
      experienced racism of Caribbean English (results not statistically significant),
      but not of Caribbean Americans. By comparing mutually adjusted Caribbean and
      black ethnic density effects in the US and England, this study examined the
      social construction of race and ethnicity as it depends on the racialised and
      stigmatised meaning attributed to it, and the association that these different
      racialised identities have on health.

PMID- 22591823
TI  - Residential property values are associated with obesity among women in King
      County, WA, USA.
AB  - Studies of social determinants of weight and health in the US have typically
      relied on self-reported education and incomes as the two primary measures of
      socioeconomic status (SES). The assessed value of one's home, an important
      component of wealth, may be a better measure of the underlying SES construct and
      a better predictor of obesity. The Seattle Obesity Study (SOS), conducted in 2008
      9, was a cross-sectional random digit dial telephone survey of 2001 adults in
      King County, Washington State, US. Participants' addresses were geocoded and
      residential property values for each tax parcel were obtained from the county tax
      assessor's database. Prevalence ratios of obesity by property values, education,
      and household income were estimated separately for women and men, after adjusting
      for age, race/ethnicity, household size, employment status and home ownership.
      Among women, the inverse association between property values and obesity was very
      strong and independent of other SES factors. Women in the bottom quartile of
      property values were 3.4 times more likely to be obese than women in the top
      quartile. No association between property values and obesity was observed for
      men. The present data strengthen the evidence for a social gradient in obesity
      among women. Property values may represent a novel and objective measure of SES
      at the individual level in the US. Measures based on tax assessment data will
      provide a valuable resource for future health studies.

PMID- 22591824
TI  - Challenging claims that mental illness has been increasing and mental well-being
      declining.
AB  - There has been a tendency by some social scientists and the media to claim that
      in advanced western societies like Britain and the US mental illness has been
      increasing and mental well-being declining over the period since the Second World
      War. In this paper I consider the evidence that is invoked in making such claims,
      along with the counter-evidence. In order to assess the evidence it is essential
      to take account of the different ways mental illness and mental well-being are
      measured and the definitions the measures embed. I argue that when the findings
      from studies using similar measures at different points in time are compared,
      there is little evidence of consistent secular increases in mental illness or
      declines in mental well-being. I suggest that such claims are encouraged by two
      main factors: first and most importantly, the major changes that have occurred in
      the official boundaries of mental disorder over the post-war period, which have
      also changed the ideas and perceptions of professionals and the public about
      mental health and illness; and second, the ready way in which data on mental
      health and illness can be used to support criticism of certain features of
      present-day society.

PMID- 22591825
TI  - Parental employment and work-family stress: associations with family food
      environments.
AB  - Parental employment provides many benefits to children's health. However, an
      increasing number of studies have observed associations between mothers' full
      time employment and less healthful family food environments. Few studies have
      examined other ways in which parental employment may be associated with the
      family food environment, including the role of fathers' employment and parents'
      stress balancing work and home obligations. This study utilized data from Project
      F-EAT, a population-based study of a socio-demographically diverse sample of 3709
      parents of adolescents living in a metropolitan area in the Midwestern United
      States, to examine cross-sectional associations between mothers' and fathers'
      employment status and parents' work-life stress with multiple aspects of the
      family food environment. Among parents participating in Project F-EAT, 64% of
      fathers and 46% of mothers were full-time employed, while 25% of fathers and 37%
      of mothers were not employed. Results showed that full-time employed mothers
      reported fewer family meals, less frequent encouragement of their adolescents'
      healthful eating, lower fruit and vegetable intake, and less time spent on food
      preparation, compared to part-time and not-employed mothers, after adjusting for
      socio-demographics. Full-time employed fathers reported significantly fewer hours
      of food preparation; no other associations were seen between fathers' employment
      status and characteristics of the family food environment. In contrast, higher
      work-life stress among both parents was associated with less healthful family
      food environment characteristics including less frequent family meals and more
      frequent sugar-sweetened beverage and fast food consumption by parents. Among
      dual-parent families, taking into account the employment characteristics of the
      other parent did not substantially alter the relationships between work-life
      stress and family food environment characteristics. While parental employment is
      beneficial for many families, identifying policy and programmatic strategies to
      reduce parents' work-life stress may have positive implications for the family
      food environment and for the eating patterns and related health outcomes of
      children and parents.

PMID- 22591826
TI  - "911" Among West African immigrants in New York City: a qualitative study of
      parents' disciplinary practices and their perceptions of child welfare
      authorities.
AB  - Immigrant parents' perceptions of child protective services may have important
      implications for their engagement in public institutions that are central to
      their children's well being. The current study examined West African immigrants'
      perceptions of child welfare authorities and the role of disciplining and
      monitoring in these communities' meaning making. A multiethnic group of 59 West
      African immigrants (32 parents and 27 adolescent children) living in the United
      States were interviewed in 18 focus groups and eight individual interviews
      between December 2009 and July 2010. Data were analyzed using a grounded theory
      approach; strategies for rigor included triangulation (multiple interview
      formats, varied composition of groups, multiple coders for each transcript),
      verification (follow-up interviewing, feedback to community-based organizations),
      and auditability. Primary among parents' concerns were "911" (used to refer to
      the police and child protective authorities), the loss of collective child
      monitoring networks, and threats to their children posed by "American" values and
      neighborhood violence. Children were concerned with parents' close monitoring
      that resulted in boredom and a sense that parents did not recognize them for
      adhering to their families' values. Feedback from CBOs suggested that parents got
      their information about child protective policies from children but that although
      misinformed they were accurate in their negative assessment of contact. Not
      unlike in other urban populations, West African immigrants' disciplinary tactics
      are instrumental, oriented toward protecting their children from the multiple
      dangers perceived in their surroundings, but may also put them at risk for
      contact with child protective services. Results suggest that "911" results from a
      "loss spiral" (Hobfoll, 1989) that begins as West Africans resettle without
      collective child monitoring networks, leading to increased concern for their
      children's safety, and interacting with a school-home disciplinary mismatch that
      may increase the likelihood of contact with child protection.

PMID- 22591827
TI  - Time changes, so do people.
AB  - When one discusses the dynamic changes in human health over time, one innately
      conceptualizes time from the three different, but related perspectives--age,
      period, and cohort. To determine their separate contributions to health outcomes,
      age-period-cohort analyses have been used for the past 80 years. This commentary
      aims to provide some insight into this analytical method by distinguishing the
      concept of time in terms of composition and context. To demonstrate, the author
      uses hypothetical nested data structures of age-period-cohort analyses in the two
      types of individual-level data, i.e., repeated cross-sectional survey and
      longitudinal data on the same individuals. The conceptual distinctions between
      composition and context have profound implications of hypothetical interventions
      in age-period-cohort analyses. Age is a compositional variable, and a
      hypothetical intervention to change age is at the individual level. By contrast,
      both period and cohort are contexts, and thus two distinct types of hypothetical
      interventions can be envisaged to examine their contextual effects. On a related
      issue, the author also discusses manipulability of time. Although time is a
      significant context in biomedical science, it is not the only context. In this
      commentary, context is proposed to be classified into three fundamental
      dimensions--relational, spatial, and temporal. Inattention to the contextual
      triad leads to a biased and precarious knowledge base for public health action,
      and the continuing flow of performance over time is an intrinsic component of
      improving our understanding of multilevel causal inference in the new era of eco
      epidemiology.

PMID- 22591828
TI  - Poverty, sexual experience and HIV vulnerability risks: evidence from Addis
      Ababa, Ethiopia.
AB  - This study explores the relationship between poverty and vulnerability to HIV
      infection in Ethiopia using primary (quantitative and qualitative) and secondary
      data from two sub-cities of Addis Ababa. The data show that sexual experience is
      influenced by diverse factors such as age, gender, economic status and education
      level. Household economic status and migration explain the nature of sexual
      experience and level of vulnerability to HIV infection. Poor uneducated women in
      poor neighbourhoods are more likely to engage in risky sexual encounters despite
      awareness about the risk of HIV infection as they operate in an environment that
      provides the 'path of least resistance' (Lindegger & Wood, 1995, p. 7). This
      article argues that poverty provides a situation where early sexual initiation,
      'transactional sex' and an inability to negotiate for safer sex are associated
      with low income, lack of education and increased vulnerability to HIV infection.
      This vulnerability is simultaneously contested and accepted as a commitment to
      even sacrifice one's life for the sake of one's loved ones. As a modest
      contribution to the 'structural violence' approach, which emphasizes social
      inequalities based on gender, class, ethnicity and race and inequalities in terms
      of exposure to risk and access to health care (Masse, 2007), this article
      challenges the 'African promiscuity' discourse, which 'does not permit
      policymakers to think beyond sex' (Stillwaggon, 2006, p. 156), and encourages
      researchers and policymakers to ask the right questions to understand the
      complexity of HIV/AIDS and seek solutions to the pandemic.

PMID- 22591829
TI  - Regional gray matter correlates of vocational interests.
AB  - BACKGROUND: Previous studies have identified brain areas related to cognitive
      abilities and personality, respectively. In this exploratory study, we extend the
      application of modern neuroimaging techniques to another area of individual
      differences, vocational interests, and relate the results to an earlier study of
      cognitive abilities salient for vocations. FINDINGS: First, we examined the
      psychometric relationships between vocational interests and abilities in a large
      sample. The primary relationships between those domains were between
      Investigative (scientific) interests and general intelligence and between
      Realistic ("blue-collar") interests and spatial ability. Then, using MRI and
      voxel-based morphometry, we investigated the relationships between regional gray
      matter volume and vocational interests. Specific clusters of gray matter were
      found to be correlated with Investigative and Realistic interests. Overlap
      analyses indicated some common brain areas between the correlates of
      Investigative interests and general intelligence and between the correlates of
      Realistic interests and spatial ability. CONCLUSIONS: Two of six vocational
      interest scales show substantial relationships with regional gray matter volume.
      The overlap between the brain correlates of these scales and cognitive-ability
      factors suggest there are relationships between individual differences in brain
      structure and vocations.

PMID- 22591830
TI  - Gelastic seizures in ring chromosome 20 syndrome: a case report with video
      illustration.
AB  - Although increasingly recognised, ring chromosome 20 (r[20]) syndrome is still
      diagnosed with delay, sometimes leading to inappropriate presurgical evaluation.
      The focal, presumed frontal, character of the seizures manifesting with fear and
      hypermotor behaviour and episodes of non-convulsive status epilepticus (NCSE) are
      most typical, as well as cognitive impairment with behavioural problems and,
      sometimes, dysmorphic signs. We present a girl diagnosed at the age of 13 years
      who suffered from an atypical clinical presentation, with minimal cognitive
      problems, absence of dysmorphic symptoms, and hypermotor/gelastic seizures.
      [Published with video sequences].

PMID- 22591831
TI  - Analgesic antidepressants promote the responsiveness of locus coeruleus neurons
      to noxious stimulation: implications for neuropathic pain.
AB  - Antidepressants that block the reuptake of noradrenaline and/or serotonin are
      among the first-line treatments for neuropathic pain, although the mechanisms
      underlying this analgesia remain unclear. The noradrenergic locus coeruleus is an
      essential element of both the ascending and descending pain modulator systems
      regulated by these antidepressants. Hence, we investigated the effect of
      analgesic antidepressants on locus coeruleus activity in Sprague-Dawley rats
      subjected to chronic constriction injury (CCI), a model of neuropathic pain. In
      vivo extracellular recordings of locus coeruleus revealed that CCI did not modify
      the basal tonic activity of this nucleus, although its sensory-evoked response to
      noxious stimuli was significantly altered. Under normal conditions, noxious
      stimulation evokes an early response, corresponding to the activation of
      myelinated A fibers, which is followed by an inhibitory period and a subsequent
      late capsaicin-sensitive response, consistent with the activation of unmyelinated
      C fibers. CCI provokes an enhanced excitatory early response in the animals and
      the loss of the late response. Antidepressant administration over 7 days
      (desipramine, 10mg/kg/day or duloxetine, 5mg/kg/day, delivered by osmotic
      minipumps) decreased the excitatory firing rate of the early response in the CCI
      group. Moreover, in all animals, these antidepressants reduced the inhibitory
      period and augmented the late response. We propose that N-methyl-d-aspartate and
      alpha-2-adrenoceptors are involved in the analgesic effect of antidepressants.
      Antidepressant-mediated changes were correlated with behavioral effects
      indicative of analgesia in healthy and neuropathic rats.

PMID- 22591832
TI  - Shedding light on Salmonella carriers.
AB  - Host-to-host transmission in most Salmonella serovars occurs primarily via the
      fecal-oral route. Salmonella enterica serovar Typhi is a human host-adapted
      pathogen and some S. Typhi patients become asymptomatic carriers. These
      individuals excrete large numbers of the bacteria in their feces and transmit the
      pathogen by contaminating water or food sources. The carrier state has also been
      described in livestock animals and is responsible for food-borne epidemics.
      Identification and treatment of carriers are crucial for the control of disease
      outbreaks. In this review, we describe recent advances in molecular profiling of
      human carriers and the use of animal models to identify potential host and
      bacterial genes involved in the establishment of the carrier state.

PMID- 22591833
TI  - Skin prick testing with extensively heated milk or egg products helps predict the
      outcome of an oral food challenge: a retrospective analysis.
AB  - BACKGROUND: Cow's milk and hen's egg are the most frequently encountered food
      allergens in the pediatric population. Skin prick testing (SPT) with commercial
      extracts followed by an oral food challenge (OFC) are routinely performed in the
      diagnostic investigation of these children. Recent evidence suggests that milk
      allergic and/or egg-allergic individuals can often tolerate extensively heated
      (EH) forms of these foods. This study evaluated the predictive value of a
      negative SPT with EH milk or egg in determining whether a child would tolerate an
      OFC to the EH food product. METHODS: Charts from a single allergy clinic were
      reviewed for any patient with a negative SPT to EH milk or egg, prepared in the
      form of a muffin. Data collected included age, sex, symptoms of food allergy, co
      morbidities and the success of the OFC to the muffin. RESULTS: Fifty-eight
      patients had negative SPTs to the EH milk or egg in a muffin and underwent OFC to
      the appropriate EH food in the outpatient clinic. Fifty-five of these patients
      tolerated the OFC. The negative predictive value for the SPT with the EH food
      product was 94.8%. CONCLUSIONS: SPT with EH milk or egg products was predictive
      of a successful OFC to the same food. Larger prospective studies are required to
      substantiate these findings.

PMID- 22591834
TI  - Environmental assessment of the milk life cycle: the effect of packaging
      selection and the variability of milk production data.
AB  - Milk is a very important part of our diet, which is why there is a wide variety
      of packaging alternatives with considerable local variants on the market. This
      study assesses the environmental impact of the commonest packaging options on the
      Spanish market and evaluates (from the point of view of global warming and
      acidification) the production of the various packaging materials and sizes and
      their final disposal (landfilling, incineration and recycling). For the two
      indicators studied (global warming and acidification) larger aseptic carton
      packages and recycling disposal have the best environmental impact. The global
      warming and acidification potential of the milk life cycle were also studied:
      milk production, transport (local conditions), packaging production and packaging
      disposal. Of the two indicators studied, the milk production stage has the
      largest impact on the milk life cycle. It should be taken into account that the
      impact of the milk production stage can vary considerably and has a significant
      influence on the global warming and acidification potential of the milk life
      cycle.

PMID- 22591835
TI  - Increased capacity to delay reward in anorexia nervosa.
AB  - Individuals with anorexia nervosa (AN) are often characterized as possessing
      excessive self-control and are unusual in their ability to reduce or avoid the
      consumption of palatable foods. This behavior promotes potentially life
      threatening weight loss and suggests disturbances in reward processing. We
      studied whether individuals with AN showed evidence of increased self-control by
      examining the tendency to delay receipt of a monetary, non-food related, reward.
      Underweight AN (n = 36) and healthy controls (HC, n = 28) completed a monetary
      intertemporal choice task measuring delay discounting factor. Individuals with AN
      reduced the value of a monetary reward over time significantly less than HC
      (F[1,61] = 5.03; p = 0.029). Secondary analyses indicated that the restricting
      subtype of AN, in particular, showed significantly less discounting than HC
      (F[1,46] = 8.3; p = 0.006). These findings indicate that some individuals with AN
      show less temporal discounting than HC, suggestive of enhanced self-control that
      is not limited to food consumption. This is in contrast to other psychiatric
      disorders, for example, substance abuse, which are characterized by greater
      discounting. Though preliminary, these findings suggest that excessive self
      control may contribute to pathological processes and individuals with AN may have
      neuropsychological characteristics that enhance their ability to delay reward and
      thereby may help to maintain persistent food restriction.

PMID- 22591836
TI  - Harmonizing disease prevention and police practice in the implementation of HIV
      prevention programs: Up-stream strategies from Wilmington, Delaware.
AB  - INTRODUCTION: Improving access to sterile injection equipment is a key component
      in community-based infectious disease prevention. Implementation of syringe
      access programs has sometimes been complicated by community opposition and police
      interference. CASE DESCRIPTION: In 2006, the Delaware legislature authorized a
      pilot syringe exchange program (SEP). A program designed to prevent, monitor, and
      respond to possible policing and community barriers before they had a chance to
      effect program implementation and operation. A program designed to prevent,
      monitor, and respond to these barriers was planned and implemented by a
      multidisciplinary team of legal practitioners and public health professionals.
      DISCUSSION: We report on an integrated intervention to address structural
      barriers to syringe exchange program utilization. This intervention employs
      community, police and client education combined with systematic surveillance of
      and rapid response to police interference to preempt the kinds of structural
      barriers to implementation observed elsewhere. The intervention addresses
      community concerns and stresses the benefits of syringe exchange programs to
      officer occupational safety. CONCLUSIONS: A cohesive effort combining
      collaboration with and educational outreach to police and community members based
      on the needs and concerns of these groups as well as SEP clients and potential
      clients helped establish a supportive street environment for the SEP. Police
      driven structural barriers to implementation of public health programs targeting
      populations engaged in drug use and other illicit behavior can be addressed by up
      stream planning, prevention, monitoring and intervention strategies. More
      research is needed to inform the tailoring of interventions to address police
      driven barriers to HIV prevention services, especially among marginalized
      populations.

PMID- 22591837
TI  - Impact of an antimicrobial stewardship programme on patient safety in Singapore
      General Hospital.
AB  - Whilst studies have shown that antimicrobial stewardship programmes (ASPs) can
      effectively reduce antibiotic utilisation, cost of care and even antimicrobial
      resistance rates, ASPs should avoid the perception that the goal is primarily to
      reduce antibiotic purchases and costs, instead of focusing on improving the
      quality of care. In addition, to address the concern of primary physicians who
      deemed that ASPs' choices of antibiotics were often inadequate, the impact of
      ASPs on patient safety should be monitored and evaluated. The aim of this study
      was to analyse the impact of ASP interventions on patient safety in Singapore
      General Hospital (SGH), a 1559-bed, large, acute, tertiary-care hospital in
      Singapore. A retrospective database review of data on ASP interventions issued
      between October 2008 and September 2010 was performed. The database maintained by
      the ASP team detailed patients' demographic data as well as outcomes of issued
      interventions. The ASP recommended 1256 interventions in a total of 1249
      admissions in six departments. Shorter average length of stay (mean +/- standard
      deviation 19.4 +/- 19.9 days vs. 24.2 +/- 24.2 days) was observed among patients
      of physicians who accepted ASP suggestions compared with patients of physicians
      who rejected ASP interventions (P<0.01). ASP interventions did not alter all
      cause mortality (P=0.191). In addition, the number of infection-related re
      admissions (P<0.001) and the 14-day re-infection rate (P=0.009) were higher among
      patients whose physicians rejected ASP interventions. In conclusion,
      interventions recommended by the ASP in SGH were safe and were associated with a
      reduction in the duration of hospital stay, 14-day re-infection rate and
      infection-related re-admissions.

PMID- 22591838
TI  - Effects of amiodarone and posaconazole on the growth and ultrastructure of
      Trypanosoma cruzi.
AB  - The antifungal posaconazole (PCZ) is the most advanced candidate for the
      treatment of Chagas disease, having potent anti-Trypanosoma cruzi activity in
      vitro and in animal models of the disease as well as an excellent safety profile
      in humans. Amiodarone (AMD) is the antiarrhythmic drug most frequently used for
      the symptomatic treatment of chronic Chagas disease patients, but it also has
      specific anti-T. cruzi activity. When used in combination, these drugs exhibit
      potent synergistic activity against the parasite. In the present work, electron
      microscopy was used to analyse the effects of both compounds, acting individually
      or in combination, against T. cruzi. The 50% inhibitory concentration (IC(50))
      against epimastigote and amastigote forms was 25 nM and 1.0 nM for PCZ and 8 MUM
      and 5.6 MUM for AMD, respectively. The antiproliferative synergism of the drugs
      (fractional inhibitory concentration<0.5) was confirmed and the ultrastructural
      alterations in the parasite induced by them, leading to cell death, were
      characterised using electron microscopy. These alterations include intense
      wrinkling of the protozoan surface, swelling of the mitochondrion, shedding of
      plasma membrane vesicles, the appearance of vesicles in the flagellar pocket,
      alterations in the kinetoplast, disorganisation of the Golgi complex,
      accumulation of lipid inclusions in the cytoplasm, and the formation of
      autophagic vacuoles, the latter confirmed by immunofluorescence microscopy. These
      findings indicate that the association of PCZ and AMD may constitute an effective
      anti-T. cruzi therapy with low side effects.

PMID- 22591839
TI  - Oseltamivir-resistant influenza A(H1N1) 2009 virus in Greece during the post
      pandemic 2010-2011 season.
AB  - Information on the drug susceptibility of influenza epidemic strains is important
      for antiviral resistance monitoring. In Greece, the 2009-2010 pandemic waves were
      very mild and seroprevalence rates remained low after this influenza season,
      resulting in exclusive detection of the pandemic strain during the 2010-2011
      influenza season. In the present study during the post-pandemic 2010-2011 season,
      50 consecutive influenza A(H1N1) 2009 virus-positive samples from patients
      hospitalised in Greek hospitals were analysed for resistance to the neuraminidase
      inhibitor oseltamivir. All patients were hospitalised with severe influenza
      complications and had previously received oseltamivir. Influenza A(H1N1) 2009
      virus detection and testing for oseltamivir resistance were performed with real
      time PCR amplification assays. The H275Y substitution associated with resistance
      to oseltamivir was identified in two immunocompetent patients who received
      oseltamivir treatment for 3 days and 5 days, respectively. In both cases,
      patients were discharged in good condition despite development of resistance to
      antiviral treatment.

PMID- 22591840
TI  - Trends in approval of new antimicrobial agents in India compared with the USA.

PMID- 22591841
TI  - Transcriptome modification of white blood cells after dietary administration of
      curcumin and non-steroidal anti-inflammatory drug in osteoarthritic affected
      dogs.
AB  - The dietary effect of non-steroidal anti-inflammatory drug (NSAID) or curcumin on
      the gene expression of peripheral white blood cells in osteoarthritis (OA)
      affected dogs was investigated using a 44K oligo microarray. Two groups of OA
      dogs and one group of healthy dogs (6 dogs each) were clinically evaluated and
      blood was sampled before (T0) and after 20days (T20) of dietary administration of
      NSAID (NSAID group) or curcumin (CURCUMIN group). Differentially expressed genes
      (P<0.05) in comparison to the control group were identified with MeV software and
      were functional annotated and monitored for signaling pathways and candidate
      biomarkers using the Ingenuity Pathways Analysis (IPA). After 20days of
      treatment, the differentially expressed transcripts significantly (P<0.05)
      decreased from 475 to 173 in NSAID group and from 498 to 141 in CURCUMIN group.
      Genes involved in "inflammatory response" and in "connective tissue development
      and function" dramatically decreased at T20. Other genes, included in "cellular
      movement", "cellular compromise" and "immune cell trafficking", were
      differentially expressed at T0 but not at T20 in both groups. Specific molecular
      targets of CURCUMIN, not observed for NSAID, were the IkB up regulation in the
      "TNRF1 signaling pathway" and IL18 down regulation in the "role of cytokines in
      mediating communication between immune cells". The activity of CURCUMIN was also
      evidenced from the inhibition of macrophages proliferation (HBEGF), related to a
      strong down regulation of TNFalpha and to activation of fibrinolysis (SERPINE1).
      The results would suggest that curcumin offers a complementary antinflammatory
      support for OA treatment in dogs.

PMID- 22591842
TI  - Repressive processing of antihypertensive peptides, Val-Pro-Pro and Ile-Pro-Pro,
      in Lactobacillus helveticus fermented milk by added peptides.
AB  - Lactobacillus helveticus can release the antihypertensive peptides, Val-Pro-Pro
      (VPP) and Ile-Pro-Pro (IPP), from casein in fermented milk by a specific
      proteolytic system. To better understand the regulation of gene expression of the
      proteolytic enzymes thought to link to the processing of both antihypertensive
      peptides in L. helveticus, microarray analysis for whole gene expression in the
      presence and absence of added peptides in the fermented milk was studied. The
      productivity of both VPP and IPP in L. helveticus CM4 fermented milk was
      repressed by adding 2% quantity of Peptone as peptide mixture to the milk. Among
      the selected 13 amino acids, Gly, Ile, Leu, Phe, Met, Ser and Val were effective
      in the repression of the productivity of VPP and IPP in the fermented milk. The
      activity of the cell wall-associated proteinase, which may play a key role in the
      processing of the two antihypertensive peptides, was significantly repressed by
      the addition of the 2% quantity of Peptone into the fermented milk. By DNA
      microarray analysis it was found that prtH2 corresponding to the cell wall
      associated proteinase gene, most of the endopeptidase genes such as pepE, pepO1,
      pepO2 and pepO3, most of the oligopeptide transporter genes, such as dppA2, dppB,
      dppC, dppD and dppF, most likely involved in the processing of VPP and IPP were
      down-regulated. These results suggest that amino acids released from milk
      peptides in the fermented milk might down-regulate the gene expressions of some
      of the proteolytic enzymes and may cause repression of the release of VPP and IPP
      in L. helveticus fermented milk.

PMID- 22591843
TI  - Characterization and crystal structure of the thermophilic ROK hexokinase from
      Thermus thermophilus.
AB  - We characterized and determined the crystal structure of a putative
      glucokinase/hexokinase from Thermus thermophilus that belongs to the ROK
      (bacterial repressors, uncharacterized open reading frames, and sugar kinases)
      family. The protein possessed significant enzymatic activity against glucose and
      mannose, with V(max) values of 260 and 68 MUmol.min(-1).mg(-1) protein,
      respectively. Therefore, we concluded that the enzyme is a hexokinase. However,
      the hexokinase showed little catalytic capacity for galactose and fructose.
      Circular dichroism measurements indicated that the enzyme was structurally stable
      at 90 degrees C. The crystal structure of the enzyme was determined at a
      resolution of 2.02 A, with R(cryst) and R(free) values of 18.1% and 22.6%,
      respectively. The polypeptide structure was divided into large and small domains.
      The ROK consensus sequences 1 and 2 were included in the large domain. The
      cysteine-rich consensus sequence 2 folded into a zinc finger, and the bound zinc
      was confirmed by both electron density and X-ray absorption fine structure (XAFS)
      spectrum. The overall structure was a homotetramer that consisted of a dimer of
      dimers. The accessible surface area buried by the association of the dimers into
      the tetrameric structures was significantly higher in the T. thermophilus enzyme
      than in a homologous tetrameric ROK sugar kinase.

PMID- 22591844
TI  - Sugar consumption and ethanol fermentation by transporter-overexpressed xylose
      metabolizing Saccharomyces cerevisiae harboring a xyloseisomerase pathway.
AB  - Four kinds of transporters, HXT1 and HXY7 from Saccharomyces cerevisiae, and GXF1
      and GXS1 from Candida intermedia, were overexpressed in xylose-metabolizing S.
      cerevisiae harboring a xyloseisomerase-based pathway. Overexpression of
      transporter enhanced sugar consumption and ethanol production, and GXF1 was
      efficient for ethanol fermentation from both glucose and xylose.

PMID- 22591845
TI  - Determination of co-metabolism for 1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane
      (DDT) degradation with enzymes from Trametes versicolor U97.
AB  - Trametes versicolor U97 isolated from nature degraded 73% of the 1,1,1-trichloro
      2,2-bis(4-chlorophenyl) ethane (DDT) in a malt extract liquid medium after a 40-d
      incubation period. This paper presents a kinetic study of microbial growth using
      the Monod equation. T. versicolor U97 degraded DDT during an exponential growth
      phase, using glucose as a carbon source for growth. The growth of T. versicolor
      U97 was not affected by DDT. DDT was degraded by T. versicolor U97 only when the
      secondary metabolism coincided with the production of several enzymes.
      Furthermore, modeling of several inhibitors using the partial least squares
      function in Minitab 15, revealed lignin peroxidase (98.7 U/l) plays a role in the
      degradation of DDT. T. versicolor U97 produced several metabolites included a
      single-ring aromatic compound, 4-chlorobenzoic acid.

PMID- 22591846
TI  - EDTA and HCl leaching of calcareous and acidic soils polluted with potentially
      toxic metals: remediation efficiency and soil impact.
AB  - The environmental risk of potentially toxic metals (PTMs) in soil can be
      diminished by their removal. Among the available remediation techniques, soil
      leaching with various solutions is one of the most effective but data about the
      impact on soil chemical and biological properties are still scarce. We studied
      the effect of two common leaching agents, hydrochloric acid (HCl) and a chelating
      agent (EDTA) on Pb, Zn, Cd removal and accessibility and on physico-chemical and
      biological properties in one calcareous, pH neutral soil and one non-calcareous
      acidic soil. EDTA was a more efficient leachant compared to HCl: up to 133-times
      lower chelant concentration was needed for the same percentage (35%) of Pb
      removal. EDTA and HCl concentrations with similar PTM removal efficiency
      decreased PTM accessibility in both soils but had different impacts on soil
      properties. As expected, HCl significantly dissolved carbonates from calcareous
      soil, while EDTA leaching increased the pH of the acidic soil. Enzyme activity
      assays showed that leaching with HCl had a distinctly negative impact on soil
      microbial and enzyme activity, while leaching with EDTA had less impact. Our
      results emphasize the importance of considering the ecological impact of
      remediation processes on soil in addition to the capacity for PTM removal.

PMID- 22591847
TI  - Biomass accumulation modelling in a highly loaded biotrickling filter for
      hydrogen sulphide removal.
AB  - A pilot scale test on a biotrickling filter packed with polyurethane foam cubes
      was carried out for 110 d at high volumetric mass load (up to 280 g m(bed)(-3) h(
      1)) with the aim of studying the accumulation of solids in the treatment of
      H(2)S. Removal rate up to 245 g m(bed)(-3) h(-1) was obtained; however, an
      accumulation of gypsum, elemental sulphur and, above all, inert biomass was
      identified as the cause of an increased pressure drop over the long term. A
      mathematical model was applied and calibrated with the experimental results to
      describe the accumulation of biomass. The model was capable of describing the
      accumulation of solids and, corresponding to a solids retention time of 50 d, the
      observed yield resulted in 0.07 g of solids produced g(-1) H(2)S removed.
      Respirometric tests showed that heterotrophic activity is inhibited at low pH (pH
      < 2.3), and the contribution to biomass removal through decay was negligible.

PMID- 22591848
TI  - Minimization of the formation of disinfection by-products.
AB  - The drinking water industry is required to minimize DBPs levels while ensuring
      adequate disinfection. In this study, efficient and appropriate treatment scheme
      for the reduction of disinfection by-product (DBPs) formation in drinking water
      containing natural organic matter has been established. This was carried out by
      the investigation of different treatment schemes consisting of enhanced
      coagulation, sedimentation, disinfection by using chlorine dioxide/ozone,
      filtration by sand filter, or granular activated carbon (GAC). Bench scale
      treatment schemes were applied on actual samples from different selected sites to
      identify the best conditions for the treatment of water. Samples were collected
      from effluent of each step in the treatment train in order to analyze pH, UV
      absorbance at 254 nm (UVA(254)), specific UV absorbance at 254 nm (SUVA(254)),
      dissolved organic carbon (DOC), haloacetic acids (HAAs) and trihalomethanes
      (THMs). The obtained results indicated that using pre-ozonation/enhanced
      coagulation/activated carbon filtration treatment train appears to be the most
      effective method for reducing DBPs precursors in drinking water treatment.

PMID- 22591849
TI  - Adsorption of Pb(II) on variable charge soils amended with rice-straw derived
      biochar.
AB  - Two Ultisols and one Oxisol from tropical regions of southern China were
      incubated with rice straw biochar to investigate the effect of biochar on their
      surface charge and Pb(II) adsorption using batch methods. The incorporation of
      biochar induced a remarkable increase in soil cation exchange capacity after 30 d
      of incubation. The incorporation of biochar significantly increased the
      adsorption of Pb(II) by these variable charge soils; the enhancement of
      adsorption of Pb(II) by these soils increased with the addition level of biochar.
      Adsorption of Pb(II) involved both electrostatic and non-electrostatic
      mechanisms; however, biochar mainly increased Pb(II) adsorption through the non
      electrostatic mechanism via the formation of surface complexes between Pb(2+) and
      functional groups on biochar. There was greater enhancement of biochar on the non
      electrostatic adsorption of Pb(II) by the variable charge soils at relatively low
      pH. Therefore, the incorporation of biochar decreased the activity and
      availability of Pb(II) to plants through increased non-electrostatic adsorption
      of Pb(II) by acidic variable charge soils.

PMID- 22591850
TI  - Identification of priority pharmaceuticals in the water environment of China.
AB  - In recent years, increasing attention has been paid to the trace-level
      contamination of pharmaceuticals in the water environment all over the world.
      Considering a large number of pharmaceuticals used, it is crucial to establish a
      priority list of pharmaceuticals that should be monitored and/or treated first.
      In the present study, we developed a ranking system based on the pharmaceutical
      consumption, removal performance in the wastewater treatment plants (WWTPs) and
      potential ecological effects, and applied to the situation of China. 39
      pharmaceuticals, which had available consumption data and also been reported
      previously in the WWTPs of China, were selected as candidate pharmaceuticals.
      Among them, seventeen pharmaceuticals were considered as priority
      pharmaceuticals, out of which, erythromycin, diclofenac acid and ibuprofen, had
      the high priority. Compared with other literatures, we found that some
      pharmaceuticals given concerns to globally should also be included in the
      priority list in China; while some pharmaceuticals, not mentioned in other
      literatures, such as cefalexin, ketoconazole, should be also given prior
      consideration in China. Among all the therapeutic classes, antibiotics, which
      were grossly abused in China, contributed the most to the priority
      pharmaceuticals. However, priority antibiotics accounted for only 32% of
      candidate antibiotics, while 71% and 100% of the candidate anti-inflammatory and
      antilipidemic respectively were identified as the priority pharmaceuticals,
      indicating that antibiotics might be overanxiously considered in the previous
      studies on their behaviors in the WWTPs of China.

PMID- 22591851
TI  - Psychiatric in-patient care and suicide in England, 1997 to 2008: a longitudinal
      study.
AB  - BACKGROUND: Psychiatric in-patients are at high risk of suicide. Recent
      reductions in bed numbers in many countries may have affected this risk but few
      studies have specifically investigated temporal trends. We aimed to explore
      trends in psychiatric in-patient suicide over time. METHOD: A prospective study
      of all patients admitted to National Health Service (NHS) in-patient psychiatric
      care in England (1997-2008). Suicide rates were determined using National
      Confidential Inquiry and Hospital Episode Statistics (HES) data. RESULTS: Over
      the study period there were 1942 psychiatric in-patient suicides. Between the
      first 2 years of the study (1997, 1998) and the last 2 years (2007, 2008) the
      rate of in-patient suicide fell by nearly one-third from 2.45 to 1.68 per 100,000
      bed days. This fall in rate was observed for males and females, across
      ethnicities and diagnoses. It was most marked for patients aged 15-44 years.
      Rates also fell for the most common suicide methods, particularly suicide by
      hanging on the ward (a 59% reduction). Although the number of post-discharge
      suicides fell, the rate of post-discharge suicide may have increased by 19%. The
      number of suicide deaths in those under the care of crisis resolution/home
      treatment teams has increased in recent years to approximately 160 annually.
      CONCLUSIONS: The rate of suicide among psychiatric in-patients in England has
      fallen considerably. Possible explanations include falling general population
      rates, changes in the at-risk population or improved in-patient safety. However,
      a transfer of risk to the period after discharge or other clinical settings such
      as crisis resolution teams cannot be ruled out.

PMID- 22591852
TI  - Functional analysis of synonymous substitutions predicted to affect splicing of
      the CFTR gene.
AB  - BACKGROUND: Cystic fibrosis is caused by mutations in the cystic fibrosis
      transmembrane conductance regulator (CFTR) gene. Over 1800 CFTR mutations have
      been reported, and about 12% of mutations are believed to impair pre-mRNA
      splicing. Given that several synthetic, non-splice-junction synonymous
      substitutions have been reported to alter splicing in CFTR, we predicted that
      naturally occurring synonymous substitutions may be erroneously classified as
      functionally neutral. METHODS: Computational tools were used to predict the
      effect of synonymous substitutions on CFTR pre-mRNA splicing. The functional
      consequences of selected substitutions were evaluated using a minigene splicing
      assay. RESULTS: Two synonymous mutations were shown to have a dramatic effect on
      CFTR pre-mRNA splicing, and consequently could alter protein integrity and
      phenotypic outcome. CONCLUSIONS: Traditional methods of mutation analysis
      overlook splicing defects that occur at internal positions in coding exons,
      especially synonymous substitutions. We show that bioinformatics tools and
      minigene splicing assays are a potent combination to prioritize and identify
      mutations that cause aberrant CFTR pre-mRNA splicing.

PMID- 22591853
TI  - Suicidality and sexual orientation among men in Switzerland: findings from 3
      probability surveys.
AB  - Few population-based surveys in Europe have examined the link between suicidality
      and sexual orientation. The objective of this study was to assess the prevalences
      of and risk for suicidality by sexual orientation, especially among adolescent
      and young adult men. Data came from three probability-based surveys in
      Switzerland from 2002: 1) Geneva Gay Men's Health Survey (GGMHS) with 571
      gay/bisexual men, 2) Swiss Multicenter Adolescent Survey on Health (SMASH) with
      7,428 16-20 year olds, and 3) Swiss Recruit Survey (ch-x) with 22,415 new
      recruits. In GGMHS, suicidal ideation (12 months/lifetime) was reported by
      22%/55%, suicide plans 12%/38%, and suicide attempts 4%/19%. While lifetime
      prevalences and ratios are similar across age groups, men under 25 years reported
      the highest 12-month prevalences for suicidal ideation (35.4%) and suicide
      attempts (11.5%) and the lowest attempt ratios (1:1.5 for attempt to plan and
      1:3.1 for attempt to ideation). The lifetime prevalence of suicide attempts among
      homo/bisexual men aged 16-20 years varies from 5.1% in ch-x to 14.1% in SMASH to
      22.0% in GGMHS. Compared to their heterosexual counterparts, significantly more
      homo/bisexual men reported 12-month suicidal ideation, plans, and attempts (OR =
      2.09-2.26) and lifetime suicidal ideation (OR = 2.15) and suicide attempts (OR =
      4.68-5.36). Prevalences and ratios vary among gay men by age and among young men
      by both sexual orientation and study population. Lifetime prevalences and ratios
      of non-fatal suicidal behaviors appear constant across age groups as is the
      increased risk of suicidality among young homo/bisexual men.

PMID- 22591854
TI  - Design, synthesis, anti-HIV evaluation and molecular modeling of piperidine
      linked amino-triazine derivatives as potent non-nucleoside reverse transcriptase
      inhibitors.
AB  - A novel series of piperidine-linked amino-triazine derivatives were designed,
      synthesized and evaluated for in vitro anti-HIV activity as non-nucleoside
      reverse transcriptase inhibitors on the basis of our previous work. Screening
      results indicated that most compounds showed excellent activity against wild-type
      HIV-1 with EC(50) values in low nanomolar concentration range (especially
      compound 6b3, EC(50) = 4.61 nM, SI = 5945) and high activity against K103N/Y181C
      resistant mutant strain of HIV-1 with EC(50) values in low micromolar
      concentration range. In addition, preliminary structure-activity relationship and
      molecular modeling of these new analogs were detailed in this manuscript.

PMID- 22591855
TI  - Targeting of polyplex to human hepatic cells by bio-nanocapsules, hepatitis B
      virus surface antigen L protein particles.
AB  - We have previously demonstrated that lipoplex, a complex of cationic liposomes
      and DNA, could be targeted to human hepatic cells in vitro and in vivo by
      conjugation with bio-nanocapsules (BNCs) comprising hepatitis B virus (HBV)
      surface antigen L protein particles. Because the BNC-lipoplex complexes were
      endowed with the human hepatic cell-specific infection machinery from HBV, the
      complexes showed excellent specific transfection efficiency in human hepatic
      cells. In this study, we have found that polyplex (a complex of polyethyleneimine
      (PEI) and DNA) could form stable complexes with BNCs spontaneously. The diameter
      and zeta-potential of BNC-polyplex complexes are about 240 nm and +3.54 mV,
      respectively, which make them more suitable for in vivo use than polyplex alone.
      BNC-polyplex complexes with an N/P ratio (the molar ratio of the amine group of
      PEI to the phosphate group of DNA) of 40 showed excellent transfection efficiency
      in human hepatic cells. When acidification of endosomes was inhibited by
      bafilomycin A1, the complexes showed higher transfection efficiency than polyplex
      itself, strongly suggesting that the complexes escaped from endosomes by both
      fusogenic activity of BNCs and proton sponge activity of polyplex. Furthermore,
      the cytotoxicity is comparable to that of polyplex of the same N/P value. Thus,
      BNC-polyplex complexes would be a promising gene delivery carrier for human liver
      specific gene therapy.

PMID- 22591856
TI  - The AP2-like gene NsAP2 from water lily is involved in floral organogenesis and
      plant height.
AB  - APETALA2 (AP2) genes are ancient and widely distributed among the seed plants,
      and play an important role during the plant life cycle, acting as key regulators
      of many developmental processes. In this study, an AP2 homologue, NsAP2, was
      characterized from water lily (Nymphaea sp. cv. 'Yellow Prince') and is believed
      to be rather primitive in the evolution of the angiosperms. In situ RNA
      hybridization showed that NsAP2 transcript was present in all regions of the
      floral primordium, but had the highest level in the emerging floral organ
      primordium. After the differentiation of floral organs, NsAP2 was strongly
      expressed in sepals and petals, while low levels were found in stamens and
      carpels. The NsAP2 protein was suggested to be localized in the cell nucleus by
      onion transient expression experiment. Overexpression of NsAP2 in Arabidopsis led
      to more petal numbers, and Arabidopsis plants expressing NsAP2 exhibited higher
      plant height, which may be a result of down-regulated expression of GA2ox2 and
      GA2ox7. Our results indicated that the NsAP2 protein may function in flower
      organogenesis in water lily, and it is a promising gene for plant height
      improvement.

PMID- 22591857
TI  - Identification of nuclear localization signal in ASYMMETRIC LEAVES2
      LIKE18/LATERAL ORGAN BOUNDARIES DOMAIN16 (ASL18/LBD16) from Arabidopsis.
AB  - The ASYMMETRIC LEAVES2-LIKE/LATERAL ORGAN BOUNDARIES DOMAIN (ASL/LBD) gene family
      encodes proteins harboring a conserved plant-specific LOB domain. The LOB domain
      contains a four-Cys motif, a Gly-Ala-Ser (GAS) block, and a Leu-zipper-like
      coiled-coil motif. The ASL/LBD proteins are a unique class of transcription
      factors that play roles in lateral organ development of plants. Although the
      ASL/LBD proteins are localized in the nucleus, no consensus sequence for the
      nuclear localization of the ASL/LBD proteins could be found. In the present
      study, we determined the motifs responsible for the nuclear localization of
      ASL18/LBD16 by using protoplast transfection assays with a variety N- or C
      terminal deletion polypeptide fragments and the polypeptides harboring changes in
      basic amino acids that are fused to enhanced green fluorescent protein. The
      results demonstrated that ASL18/LBD16 harbors two distinct domains comprising an
      atypical nuclear localization signal (NLS) with basic amino acid residues in the
      coiled-coil motif and a monopartite-like NLS in the C-terminal region for nuclear
      targeting.

PMID- 22591858
TI  - Cryo-tolerance of zygotic embryos from recalcitrant seeds in relation to
      oxidative stress--a case study on two amaryllid species.
AB  - Oxidative stress is a major component of cryoinjury in plant tissues. This study
      investigated the ability of recalcitrant (i.e. desiccation sensitive) Amaryllis
      belladonna L. and Haemanthus montanus Baker zygotic embryos to survive
      cryopreservation, in relation to oxidative stress. The study also investigated
      whether glycerol cryoprotection promoted embryo post-cryo survival by protecting
      enzymic antioxidant activities. Zygotic embryos excised from hydrated stored
      seeds were subjected to various combinations of rapid dehydration (to < or >0.4 g
      g-1 [dmb]), cryoprotection (with sucrose or glycerol), and cooling (either
      rapidly or slowly), and were thereafter assessed for viability, extracellular
      superoxide (.O2-) production, lipid peroxidation (TBARS) and antioxidant enzyme
      activities. Short-term hydrated storage of whole seeds was accompanied by .O2-
      production and lipid peroxidation, but .O2- levels were lower than in dehydrated
      and cooled embryos and viability was 100%, possibly associated with the high
      activities of certain antioxidant enzymes. Partial dehydration and cryoprotection
      (in H. montanus only) increased .O2- production (especially in cryoprotected
      dried embryos) and was associated with some viability loss, but this was not
      correlated with enhanced lipid peroxidation. Cooling was generally accompanied by
      the greatest increase in .O2- production, and with a decline in viability. In A.
      belladonna only, post-cryo TBARS levels were generally higher than for fresh and
      pre-conditioned embryos. Partial dehydration and cooling decreased antioxidant
      activities, but these were consistently less severe in glycerol cryoprotected
      dried, as opposed to non-cryoprotected-dried embryos. Post-cryo viability
      retention for glycerol cryoprotected-dried embryos was significantly higher than
      for non-cryoprotected-dried embryos, possibly facilitated by relatively low post
      drying TBARS levels and high post-drying and post-rewarming activities of some
      antioxidant enzymes in the former. Pre-conditioning treatments such as glycerol
      cryoprotection, when used in combination with partial drying, may enhance post
      cryo viability retention in recalcitrant zygotic embryos by protecting the
      activities of certain antioxidant enzymes during pre-conditioning for, and after
      retrieval from, cryostorage.

PMID- 22591859
TI  - Arapan-S: a fast and highly accurate whole-genome assembly software for viruses
      and small genomes.
AB  - BACKGROUND: Genome assembly is considered to be a challenging problem in
      computational biology, and has been studied extensively by many researchers. It
      is extremely difficult to build a general assembler that is able to reconstruct
      the original sequence instead of many contigs. However, we believe that creating
      specific assemblers, for solving specific cases, will be much more fruitful than
      creating general assemblers. FINDINGS: In this paper, we present Arapan-S, a
      whole-genome assembly program dedicated to handling small genomes. It provides
      only one contig (along with the reverse complement of this contig) in many cases.
      Although genomes consist of a number of segments, the implemented algorithm can
      detect all the segments, as we demonstrate for Influenza Virus A. The Arapan-S
      program is based on the de Bruijn graph. We have implemented a very sophisticated
      and fast method to reconstruct the original sequence and neglect erroneous k
      mers. The method explores the graph by using neither the shortest nor the longest
      path, but rather a specific and reliable path based on the coverage level or k
      mers' lengths. Arapan-S uses short reads, and it was tested on raw data
      downloaded from the NCBI Trace Archive. CONCLUSIONS: Our findings show that the
      accuracy of the assembly was very high; the result was checked against the
      European Bioinformatics Institute (EBI) database using the NCBI BLAST Sequence
      Similarity Search. The identity and the genome coverage was more than 99%. We
      also compared the efficiency of Arapan-S with other well-known assemblers. In
      dealing with small genomes, the accuracy of Arapan-S is significantly higher than
      the accuracy of other assemblers. The assembly process is very fast and requires
      only a few seconds.Arapan-S is available for free to the public. The binary files
      for Arapan-S are available through
      http://sourceforge.net/projects/dnascissor/files/.

PMID- 22591860
TI  - Developmental effects of decision-making on sensitivity to reward: an fMRI study.
AB  - Studies comparing neural correlates of reward processing across development yield
      inconsistent findings. This challenges theories characterizing adolescents as
      globally hypo- or hypersensitive to rewards. Developmental differences in reward
      sensitivity may fluctuate based on reward magnitude, and on whether rewards
      require decision-making. We examined whether these factors modulate developmental
      differences in neural response during reward anticipation and/or receipt in 26
      adolescents (14.05+/-2.37 yrs) and 26 adults (31.25+/-8.23 yrs). Brain activity
      was assessed with fMRI during reward anticipation, when subjects made responses
      with-vs.-without decision-making, to obtain large-vs.-small rewards, and during
      reward receipt. When reward-receipt required decision-making, neural activity did
      not differ by age. However, when reward receipt did not require decision-making,
      neural activity varied by development, reward magnitude, and stage of the reward
      task. During anticipation, adolescents, but not adults, exhibited greater
      activity in the insula, extending into putamen, and cingulate gyrus for large-vs.
      small incentives. During feedback, adults, but not adolescents, exhibited greater
      activity in the precuneus for large-vs.-small incentives. These data indicate
      that age-related differences in reward sensitivity cannot be characterized by
      global hypo- or hyper-responsivity. Instead, neural responding in striatum,
      prefrontal cortex and precuneus is influenced by both situational demands and
      developmental factors. This suggests nuanced maturational effects in adolescent
      reward sensitivity.

PMID- 22591861
TI  - The role of the left intraparietal sulcus in the relationship between symbolic
      number processing and children's arithmetic competence.
AB  - The neural foundations of arithmetic learning are not well understood. While
      behavioral studies have revealed relationships between symbolic number processing
      and individual differences in children's arithmetic performance, the
      neurocognitive mechanisms that bind symbolic number processing and arithmetic are
      unknown. The current fMRI study investigated the relationship between children's
      brain activation during symbolic number comparison (Arabic digits) and individual
      differences in arithmetic fluency. A significant correlation was found between
      the numerical ratio effect on reaction times and accuracy and children's
      arithmetic scores. Furthermore, children with a stronger neural ratio effect in
      the left intraparietal sulcus (IPS) during symbolic number processing exhibited
      higher arithmetic scores. Previous research has demonstrated that activation of
      the IPS during numerical magnitude processing increases over the course of
      development, and that the left IPS plays an important role in symbolic number
      processing. The present findings extend this knowledge to show that children with
      more mature response modulation of the IPS during symbolic number processing
      exhibit higher arithmetic competence. These results suggest that the left IPS is
      a key neural substrate for the relationship between the relative of precision of
      the representation of numerical magnitude and school-level arithmetic competence.

PMID- 22591863
TI  - Fire in a hospital.

PMID- 22591862
TI  - CXCL13 is the major determinant for B cell recruitment to the CSF during
      neuroinflammation.
AB  - BACKGROUND: The chemokines and cytokines CXCL13, CXCL12, CCL19, CCL21, BAFF and
      APRIL are believed to play a role in the recruitment of B cells to the central
      nervous system (CNS) compartment during neuroinflammation. To determine which
      chemokines/cytokines show the strongest association with a humoral immune
      response in the cerebrospinal fluid (CSF), we measured their concentrations in
      the CSF and correlated them with immune cell subsets and antibody levels.
      METHODS: Cytokine/chemokine concentrations were measured in CSF and serum by
      ELISA in patients with non-inflammatory neurological diseases (NIND, n = 20),
      clinically isolated syndrome (CIS, n = 30), multiple sclerosis (MS, n = 20), Lyme
      neuroborreliosis (LNB, n = 8) and patients with other inflammatory neurological
      diseases (OIND, n = 30). Albumin, IgG, IgA and IgM were measured by nephelometry.
      CSF immune cell subsets were determined by seven-color flow cytometry. RESULTS:
      CXCL13 was significantly elevated in the CSF of all patient groups with
      inflammatory diseases. BAFF levels were significantly increased in patients with
      LNB and OIND. CXCL12 was significantly elevated in patients with LNB. B cells and
      plasmablasts were significantly elevated in the CSF of all patients with
      inflammatory diseases. CXCL13 showed the most consistent correlation with CSF B
      cells, plasmablasts and intrathecal Ig synthesis. CONCLUSIONS: CXCL13 seems to be
      the major determinant for B cell recruitment to the CNS compartment in different
      neuroinflammatory diseases. Thus, elevated CSF CXCL13 levels rather reflect a
      strong humoral immune response in the CNS compartment than being specific for a
      particular disease entity.

PMID- 22591864
TI  - Putting patients first: draft guidelines for compensation for research-related
      injury in clinical trials in India.

PMID- 22591865
TI  - Do not trade away our lives.

PMID- 22591866
TI  - Expressions of equity: imbalances in the patient-clinician interaction.
AB  - This paper reports patient perceptions of inequities in the doctor-patient
      interaction. A mixed method study was conducted in a tertiary eye care centre in
      southern India to gain an insight into patient understanding and satisfaction
      from clinician communication. Non-participant observations enabled us to map the
      sequence of communication opportunities in the clinical interaction, and in-depth
      interviews were used to identify patient perceptions of the content and clarity
      of clinician communication in a clinic for patients of glaucoma, a chronic eye
      disease. A 60-item instrument was administered to 550 participants in the
      quantitative phase to explore associations between patient expectations,
      experience and ratings of clinician communication and satisfaction with it. The
      qualitative results helped map the clinical interaction, highlighting the
      consequences of poor clinician communication. The quantitative phase showed that
      patients expected explanations about the disease, the opportunity to ask
      questions, receiving supportive signals, and being treated as equals. Most
      patients stated their information source on disease was their doctor, leading us
      to conclude that clinicians must utilise communication opportunities optimally to
      ensure every patient has an equal chance to correctly understand their disease
      and role in treatment. By consciously improving their communication and using it
      strategically, clinicians can help ensure effective treatment outcomes.

PMID- 22591867
TI  - Awareness of medical ethics among undergraduates in a West Bengal medical
      college.
AB  - This descriptive, cross-sectional study was conducted to assess the knowledge of
      and attitudes towards medical ethics among undergraduate medical students. It
      also looked at whether there was any improvement with additional years of medical
      education. 340 medical students of a medical college in West Bengal were given a
      semi-structured questionnaire that included questions regarding their awareness
      of ethics, their attitudes towards various issues in clinical ethics, and their
      knowledge of the code of medical ethics of the West Bengal Medical Council. The
      responses of 322 students were analysed by simple descriptive statistics. The
      students generally agreed that awareness of ethics was important. Lectures
      (54.7%) and books (47.8%) were their predominant sources of knowledge. Only 10.9
      % were aware of the existence of an institutional ethics committee and 42.8% did
      not know its exact role. Their answers showed that the majority of students
      expressed mixed responses--both desirable and undesirable--in relation to
      questions exploring different aspects of basic ethical reasoning in their
      professional life. The most desirable response for each statement was decided by
      experts of forensic medicine and also from a literature study. Only half the
      respondents (50.9%) had a good score (61-70 out of a total possible 90) and 37.2%
      had a fair score (51-60). There was no increase in scores corresponding with
      additional years of medical education.

PMID- 22591868
TI  - Completeness of consent forms in research proposals submitted to an ethics review
      committee.
AB  - This was a descriptive cross-sectional study which analysed the consent forms
      submitted to the ethics review committee at the faculty of medicine of the
      University of Kelaniya, Sri Lanka, between January 2007 and December 2008. Of the
      145 consent forms reviewed, 94.5% (137) explained the purpose of the study, 77%
      (111) included a statement that participation was voluntary, 44% (64) stated that
      refusal of participation did not affect care, 65.5% (95) mentioned the ability to
      withdraw consent at any time, 79% (115) that confidentiality of records would be
      maintained and 45.5% (66) that further clarifications were possible. Thirty nine
      (75%) of 52 eligible consent forms described the potential benefits and 19% (18)
      of 93 consent forms explained that there were no benefits to the participants.
      Twenty eight (59%) of 47 eligible consent forms described possible risks or
      discomfort to patients and 30% (29) of 98 consent forms explained that there were
      no risks to the participants. In conclusion, essential elements of the consent
      forms were missing in this study. It is recommended that a checklist of
      compulsory elements to include on forms be used before proposals are submitted to
      an ethics review committee.

PMID- 22591869
TI  - Psychiatric advance directives: potential challenges in India.
AB  - The advance directive is a statement of an individual's preference for future
      treatment. The concept initially evolved in the context of end-of-life treatment
      decision making. Subsequently, in some countries, advance directives have been
      promoted in the care and treatment of people with serious mental disorders. They
      have recently been endorsed by the United Nations Convention for the Rights of
      Persons with Disability. In India, the legal framework related to the care of
      persons with mental illness is currently being reappraised, and significant
      changes are being contemplated. Thus, this is an appropriate time to review the
      existing evidence on psychiatric advance directives and examine the potential
      challenges involved in making them legally binding. A wide spectrum of mental
      health 'advance statements' have been developed and implemented in some high
      resource countries. Of special interest to mental health contexts is the complex
      Ulysses contract to accommodate situations where the advance directive can be
      overridden during phases of acute illness or relapse. There have been mixed
      experiences with advance directives in the last couple of decades and there is
      scant evidence to suggest that they are effective in improving actual care. There
      has been almost no discourse in India on the issue of mental health advance
      directives. Yet this feature is being considered for implementation in the
      revised legal framework for the care of persons with mental illness. There are
      significant barriers to the feasibility and acceptability of legally mandated
      advance directives. There are logistical barriers to operationalising them in a
      manner that guarantees quality assurance of the process, and minimises the
      possibility of misuse. Thus, while the advance directive is a highly desirable
      clinical tool for collaborative decision making between the person with mental
      illness and the treatment provider, at this time, more needs to be done before
      legal enforcement is considered in India.

PMID- 22591870
TI  - Psychiatric advance directives: challenges of implementation.

PMID- 22591871
TI  - Tacit trust cannot be violated: report of the Presidential Commission for the
      Study of Bioethical Issues, USA.

PMID- 22591872
TI  - India's child sex ratio: worsening imbalance.

PMID- 22591873
TI  - Polio programme: let us declare victory and move on.
AB  - It was hoped that following polio eradication, immunisation could be stopped.
      However the synthesis of polio virus in 2002, made eradication impossible. It is
      argued that getting poor countries to expend their scarce resources on an
      impossible dream over the last 10 years was unethical. Furthermore, while India
      has been polio-free for a year, there has been a huge increase in non-polio acute
      flaccid paralysis (NPAFP). In 2011, there were an extra 47,500 new cases of
      NPAFP. Clinically indistinguishable from polio paralysis but twice as deadly, the
      incidence of NPAFP was directly proportional to doses of oral polio received.
      Though this data was collected within the polio surveillance system, it was not
      investigated. The principle of primum-non-nocere was violated. The authors
      suggest that the huge bill of US$ 8 billion spent on the programme, is a small
      sum to pay if the world learns to be wary of such vertical programmes in the
      future.

PMID- 22591874
TI  - Compensation to Bhopal gas victims: will justice ever be done?

PMID- 22591875
TI  - Who killed clinical medicine? An allegorical murder mystery.

PMID- 22591876
TI  - Treating a homeless psychiatric patient: ethical challenges.

PMID- 22591877
TI  - Ethics in burns surgery: when is enough, enough?
AB  - Patients with extensive burns injuries are often given a poor prognosis. Those
      who survive after an initial early resuscitation phase often require extensive
      operative and critical care input, a prolonged hospital stay, and associated
      significant complications. The overwhelmingly high volume of patients already
      using the resource-stricken burns care service places extreme pressure on
      clinicians in respect of decisions they make about who should and should not be
      resuscitated. In this paper, we present the case of a young woman who sustained
      significant burn injuries, and discuss the ethical dilemmas encountered during
      the subsequent management of her care.

PMID- 22591879
TI  - Internet report cards for doctors: threat or opportunity?

PMID- 22591878
TI  - Commentary: Taking decisions one can live with.

PMID- 22591880
TI  - Why should I not prescribe branded drugs?

PMID- 22591881
TI  - No dependable alternative to MCQs.

PMID- 22591882
TI  - ACCF 2012 health policy statement on patient-centered care in cardiovascular
      medicine: a report of the American College of Cardiology Foundation Clinical
      Quality Committee.

PMID- 22591883
TI  - Interactions between domestic water hardness, infant swimming and atopy in the
      development of childhood eczema.
AB  - AIM: Recent studies suggest that domestic water hardness and swimming in
      chlorinated pools may increase the prevalence of childhood eczema. The combined
      influence of these two factors as well as their interaction with atopic status
      has not been investigated. METHODS: We conducted a cross-sectional study on 358
      children aged 5-6 years (54% of boys) in 30 kindergarten schools. Parents
      completed a questionnaire about the child's health, chlorinated pool attendance
      and potential confounders. Data about tap water quality were provided by water
      companies. Atopy was defined as a sensitization to at least one aeroallergen or
      as a medication for allergy. The effect of water hardness and infant swimming
      practice were assessed by multivariate logistic models. In addition, the effects
      of these risk factors combined with atopy were evaluated using two measures of
      biological interaction: the attributable proportion of interaction (AP) and the
      synergy index (S). AP>0 and S>1 indicate biological interaction between the two
      risk factors. RESULTS: Water hardness was linearly associated to the prevalence
      of eczema whereas the relationship of eczema with infant swimming was not linear.
      We observed a biological interaction between hard water (>150 mg/L CaCO(3)L(-1))
      and atopic status that increases the prevalence of eczema with an odds ratio (OR)
      of 3.30 and a 95% confidence interval (CI) of 1.34-8.15 (AP, 0.41; 95% CI 0.15
      0.66 and S, 2.4; 95% CI 0.96-6.01). Infant swimming practice combined with atopy
      also increased the prevalence of eczema (OR, 2.72; 95% CI 1.29-5.74) although
      none of the interaction measures was significant. However, when water hardness
      and infant swimming were combined, there was no further increase of the eczema
      prevalence due to some form of antagonistic interaction between these two factors
      (AP, -0.56; 95% CI -1.12 to -0.01 and S, 0.54; 95% CI 0.33-0.87). CONCLUSIONS:
      Our study shows that exposure to hard water and infant swimming interact with
      atopic status to increase the prevalence of childhood eczema. A breaching of the
      epidermal barrier by detergents or salts in hard water and by chlorine-based
      oxidants in swimming pool water might explain these interactions.

PMID- 22591884
TI  - Systematic reviews of the role of omega-3 fatty acids in the prevention and
      treatment of disease.

PMID- 22591885
TI  - Omega 3 polyunsaturated fatty acids and body weight.
AB  - In animal studies, n-3 PUFA have been shown to influence body composition and to
      reduce the accumulation of body fat, thereby affecting body weight homeostasis.
      In addition, it has been suggested that an additional supply of n-3 PUFA during
      pregnancy or lactation, or both, would have a beneficial effect on birth weight
      and infant growth and development. The purpose of the present study was to
      systematically review interventional clinical trials on the effects of dietary n
      3 PUFA supplementation on body weight in adult subjects and in infants whose
      mothers were supplemented with these fatty acids during pregnancy and/or
      lactation. A systematic search, focused on n-3 PUFA and body weight, and limited
      to controlled clinical trials, was performed in different databases. The quality
      of all included studies was assessed against set criteria, and results of
      eligible trials were compared. There were few studies targeting this topic. In
      adults, all of the five studies included, except for one, show no change in body
      weight by dietary supplementation with n-3 PUFA. Within those trials conducted in
      pregnant and/or lactating women in which a main outcome was birth weight or
      growth in infancy, two showed a modest increase in birth weight and the rest
      showed no effect. None of the trials showed an effect of maternal n-3 PUFA
      supplementation on infant's weight at the short term. However, it should be noted
      that a number of limitations, including a variety of experimental designs, type
      and doses of n-3 PUFA, and high attrition rates, among others, make impossible to
      draw robust conclusions from this review.

PMID- 22591886
TI  - Effect of n-3 long chain polyunsaturated fatty acids during the perinatal period
      on later body composition.
AB  - A systematic review to identify studies reporting the effects of n-3 long chain
      polyunsaturated fatty acids (LCPUFA) intake, during pregnancy and postnatally, on
      infants and young children's body composition was performed. A structured search
      strategy was performed in the MEDLINE (PubMed), EMBASE, and LILACS databases.
      Inclusion and exclusion criteria were defined according to the research question.
      Only those studies addressing the relationship between n-3 LCPUFA exposure during
      the perinatal period and later adiposity measured in terms of weight, height,
      body mass index (BMI), skinfold thickness and/or circumferences were included
      regardless of the study design. Studies quality was scored and were thereafter
      categorised into those reporting on maternal intake of n-3 LCPUFA during
      pregnancy or lactation (6 publications) or on infant's n-3 LCPUFA intake (7
      publications). Two studies showed inverse associations between maternal n-3
      LCPUFA intake and children's later body composition (lower adiposity, BMI or body
      weight), two showed direct associations and no effects were observed in the
      remaining two studies. Among those studies focusing on n-3 LCPUFA intake through
      enriched infant formulas; three observed no effect on later body composition and
      two showed higher weight and adiposity with increased amounts of n-3 LCPUFA.
      Reversely, in two studies weight and fat mass decreased. In conclusion, reported
      body composition differences in infants and young children were not clearly
      explained by perinatal n-3 LCPUFA intake via supplemented formulas, breastfeeding
      or maternal intakes of n-3 LCPUFA during pregnancy and lactation. Associated
      operational mechanisms including n-3 LCPUFA doses and sources applied are not
      sufficiently explained and therefore no conclusions could be made.

PMID- 22591887
TI  - Omega 3 fatty acids and inborn errors of metabolism.
AB  - A number of studies are investigating the role of n-3 polyunsaturated fatty acids
      in children with metabolic inborn errors, while the effects on visual and brain
      development in premature infants and neonates are well known. However, their
      function incertain chronic neurological, inflammatory and metabolic disorders is
      still under study. Standards should be established to help identify the need of
      docosahexaenoic acid supplementation in conditions requiring a restricted diet
      resulting in an altered metabolism system, and find scientific evidence on the
      effects of such supplementation. This study reviews relevant published literature
      to propose adequate n-3 intake or supplementation doses for different ages and
      pathologies. The aim of this review is to examine the effects of long chain
      polyunsaturated fatty acids supplementation in preventing cognitive impairment or
      in retarding its progress, and to identify nutritional deficiencies, in children
      with inborn errors of metabolism. Trials were identified from a search of the
      Cochrane and MEDLINE databases in 2011. These databases include all major
      completed and ongoing double-blind, placebo-controlled, randomized trials, as
      well as all studies in which omega-3 supplementation was administered to children
      with inborn errors, and studies assessing omega-3 fatty acids status in plasma in
      these pathologies. Although few randomized controlled trials met the inclusion
      criteria of this review, some evidenced that most of children with inborn errors
      are deficient in omega-3 fatty acids, and demonstrated that supplementation might
      improve their neural function, or prevent the progression of neurological
      impairment. Nontheless, further investigations are needed on this issue.

PMID- 22591888
TI  - Omega 3 fatty acids in the elderly.
AB  - Population ageing affects the entire world population. Also at world level one
      can observe a sharp increase in the proportion of older people. The challenge
      posed by population ageing translates into ensuring that the extra years of life
      will be as good as possible, free from high-cost dependency. Omega-3 fatty acids
      are now generally recognized as potential key nutrients to prevent the
      pathological conditions associated to the aging process. Ageing physiological
      process, its association with quality of life and the impact of omega-3 fatty
      acids intake and/or status is the focus of the present review. This report deals
      with the effects of omega-3 fatty acids on normal aging of older adults ( >= 65
      years) mainly on the effects such as nutritional status itself, cognition, bone
      health, muscle tonus, and general health status. The preliminary broad search of
      the literature on the effects of omega-3 fatty acids on normal aging yielded 685
      citations. Forty two full text papers were checked for inclusion and thirty six
      studies were finally included in this review. It may be concluded that
      paradoxically even though the elderly population is the largest one, the number
      of studies and the methodology employed clearly lacks of sufficient evidence to
      establish definite conclusions on the effects of omega-3 fatty acids on aging
      metabolism without pathological conditions and on quality of life.

PMID- 22591889
TI  - Omega 3 fatty acids and cognitive health in older people.
AB  - Oily fish and other sources of long-chain n-3 polyunsaturated fatty acids (n-3
      LCPs) have been proposed as protective against dementia and age related cognitive
      impairment. The basic mechanisms underlying these proposed benefits have been
      postulated and experimental studies supporting the plausibility of the putative
      effects have been published. Observational epidemiological and case control
      studies also largely support a protective role of fish consumption on cognitive
      function with advancing age, albeit with important unexplained heterogeneity in
      findings. In this review we report the findings of the latest Cochrane review on
      the benefits of n-3 LCP supplementation on cognitive function among cognitively
      healthy older people and expand the review by including trials conducted with
      individuals with prevalent poor cognitive function or dementia. We identified
      seven relevant trials, four among cognitively healthy older people, and three
      among individuals with pre-existing cognitive decline or dementia, and overall
      conclude that there is no evidence to support the routine use of n-3 LCPs
      supplements for the prevention, or amelioration, of cognitive decline in later
      life. We identified several challenges in the design of intervention studies for
      the prevention of dementia and cognitive decline in older people that require
      careful consideration especially in recruitment and retention in long-term
      trials. Whether the lack of agreement in findings from mechanistic and
      observational data and from intervention studies reflects a real absence of
      benefit on cognitive function from n-3 LCP supplementation, or whether it
      reflects intrinsic limitations in the design of published studies remains open to
      question.

PMID- 22591890
TI  - Omega-3 long-chain polyunsaturated fatty acids supplementation on inflammatory
      biomakers: a systematic review of randomised clinical trials.
AB  - Inflammation is part of the normal host response to infection and injury.
      Eicosanoids, cytokines, chemokines, adhesion molecules and other inflammatory
      molecules are frequently produced during this process. Numerous studies in humans
      have documented the inflammation-limiting properties of omega-3 fatty acids, but
      only a few have been randomised clinical trials. The aim of this study was to
      perform a systematic search of randomised clinical trials on omega-3 fatty acids
      and inflammatory biomarkers in all subjects including healthy and ill persons up
      to February 2011 using PubMed and LILACS databases, defined by a specific
      equation using MeSH terms and limited to randomised clinical trials; there was no
      any a priori decision to include some diseases and not others. The quality of
      each publication was validated by using the JADAD scale and the CONSORT
      checklist. Inflammatory biomarkers were considered as primary outcomes. Twenty
      six publications of the last 10 years were selected. Studies included healthy
      subjects and patients with cardiovascular disease and other chronic and acute
      diseases; all reported the number of subjects, type of study, type and doses of
      omega-3 fatty acids, main outcomes and major inflammatory biomarkers. Dietary
      omega-3 fatty acids are associated with plasma biomarker levels, reflecting lower
      levels of inflammation and endothelial activation in cardiovascular disease and
      other chronic and acute diseases, including chronic renal disease, sepsis and
      acute pancreatitis. However, further research is required before definitive
      recommendations can be made about the routine use of omega-3 fatty acids in
      critically ill patients or with neurodegenerative or chronic renal disease.

PMID- 22591891
TI  - Influence of marine n-3 polyunsaturated fatty acids on immune function and a
      systematic review of their effects on clinical outcomes in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of the
      joints and bones. The n-6 polyunsaturated fatty acid (PUFA) arachidonic acid
      (ARA) is the precursor of inflammatory eicosanoids which are involved in RA. Some
      therapies used in RA target ARA metabolism. Marine n-3 PUFAs (eicosapentaenoic
      acid (EPA) and docosahexaenoic acid (DHA)) found in oily fish and fish oils
      decrease the ARA content of cells involved in immune responses and decrease the
      production of inflammatory eicosanoids from ARA. EPA gives rise to eicosanoid
      mediators that are less inflammatory than those produced from ARA and both EPA
      and DHA give rise to resolvins that are anti-inflammatory and inflammation
      resolving, although little is known about these latter mediators in RA. Marine n
      3 PUFAs can affect other aspects of immunity and inflammation relevant to RA,
      including dendritic cell and T cell function and production of inflammatory
      cytokines and reactive oxygen species, although findings for these outcomes are
      not consistent. Fish oil has been shown to slow the development of arthritis in
      animal models and to reduce disease severity. A number of randomised controlled
      trials of marine n-3 PUFAs have been performed in patients with RA. A systematic
      review included 23 studies. Evidence is seen for a fairly consistent, but modest,
      benefit of marine n-3 PUFAs on joint swelling and pain, duration of morning
      stiffness, global assessments of pain and disease activity, and use of non
      steroidal anti-inflammatory drugs.

PMID- 22591892
TI  - The effect of EPA and DHA on metabolic syndrome patients: a systematic review of
      randomised controlled trials.
AB  - Metabolic syndrome (MS) is characterised by accumulation of CVD risk factors. The
      use of very long chain n-3 polyunsaturated fatty acids (VLC n3 PUFA) could
      potentially benefit MS by reducing risk factors. To better understand the
      possible VLC n3 PUFA benefits, the literature was systematically reviewed for
      randomised controlled trials (RCT) that published effects of VLC n3 PUFA on MS
      patients. 17 RCT fulfilled the inclusion criteria and were analysed for relevance
      to the research question. The available RCT convincingly show that the
      administration of VLC n3 PUFA doses > 1 g for at least 3 months produces a
      significant reduction of triglycerides ranging from 7 % to 25 %. These results
      confirm the hypotriglyceridemic effect of VLC n3 PUFA in MS patients. The
      triglyceride lowering may produce further benefits by reducing the % of pro
      atherogenic small dense LDL particles (sdLDL) and also perhaps by ameliorating
      the inflammatory process associated with MS. High doses of VLC n3 PUFA ( >= 3
      g/day) may produce further TAG reductions but could raise other risk factors such
      as LDL-C. No clear effects were found on other MS markers. The combination of VLC
      n3 PUFA plus a statin may be useful to prevent the occurrence of coronary events.
      More studies are needed using different amounts of VLC n3 PUFA, time lengths,
      dietary backgrounds and different profiles of MS patients before clear
      recommendations can be made.

PMID- 22591893
TI  - Omega-3 fatty acids and blood pressure.
AB  - Epidemiological and clinical studies suggest that consumption of omega (omega-3)
      polyunsaturated fatty acids (PUFA) contributes to the reduction of cardiovascular
      mortality through different mechanisms including modulation of cellular metabolic
      functions, gene expression and beneficial effects on lipid profile or blood
      pressure. The aim of the study is to review the effects of omega-3 PUFA
      supplemented as fish oil or blue fish in blood pressure. The analysis of
      different studies suggests that high doses omega-3 PUFA ( >= 3 g/day) produces a
      small but significant decrease in blood pressure, especially systolic blood
      pressure, in older and hypertensive subjects; however, the evidence is not
      consistent among different studies. omega-3 polyunsaturated fatty acids
      consumption might have a place in the control of patients with mild hypertension
      before starting drug treatment and of those who prefer changes of lifestyles like
      diet.

PMID- 22591894
TI  - Long chain omega-3 fatty acids and cardiovascular disease: a systematic review.
AB  - INTRODUCTION: Cardiovascular disease remains the commonest health problem in
      developed countries, and residual risk after implementing all current therapies
      is still high. The use of marine omega-3 fatty acids (DHA and EPA) has been
      recommended to reduce cardiovascular risk by multiple mechanisms. OBJECTIVES: To
      update the current evidence on the influence of omega-3 on the rate of
      cardiovascular events. REVIEW METHODS: We used the MEDLINE and EMBASE databases
      to identify clinical trials and randomized controlled trials of omega-3 fatty
      acids (with quantified quantities) either in capsules or in dietary intake,
      compared to placebo or usual diet, equal to or longer than 6 months, and written
      in English. The primary outcome was a cardiovascular event of any kind and
      secondary outcomes were all-cause mortality, cardiac death and coronary events.
      We used RevMan 5.1 (Mantel-Haenszel method). Heterogeneity was assessed by the I2
      and Chi2 tests. We included 21 of the 452 pre-selected studies. RESULTS: We found
      an overall decrease of risk of suffering a cardiovascular event of any kind of 10
      % (OR 0.90; [0.85-0.96], p = 0.001), a 9 % decrease of risk of cardiac death (OR
      0.91; [0.83-0.99]; p = 0.03), a decrease of coronary events (fatal and non-fatal)
      of 18 % (OR 0.82; [0.75-0.90]; p < 1 * 10-4), and a trend to lower total
      mortality (5 % reduction of risk; OR 0.95; [0.89-1.02]; p = 0.15. Most of the
      studies analyzed included persons with high cardiovascular risk. CONCLUSIONS:
      marine omega-3 fatty acids are effective in preventing cardiovascular events,
      cardiac death and coronary events, especially in persons with high cardiovascular
      risk.

PMID- 22591895
TI  - Omega-3 fatty acids and incident type 2 diabetes: a systematic review and meta
      analysis.
AB  - The relationship between omega-3 polyunsaturated fatty acids (n-3 PUFA) from
      seafood sources (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) or plant
      sources (alpha-linolenic acid, ALA) and risk of type 2 diabetes mellitus (DM)
      remains unclear. We systematically searched multiple literature databases through
      June 2011 to identify prospective studies examining relations of dietary n-3
      PUFA, dietary fish and/or seafood, and circulating n-3 PUFA biomarkers with
      incidence of DM. Data were independently extracted in duplicate by 2
      investigators, including multivariate-adjusted relative risk (RR) estimates and
      corresponding 95 % CI. Generalized least-squares trend estimation was used to
      assess dose-response relationships, with pooled summary estimates calculated by
      both fixed-effect and random-effect models. From 288 identified abstracts, 16
      studies met inclusion criteria, including 18 separate cohorts comprising 540,184
      individuals and 25,670 cases of incident DM. Consumption of fish and/or seafood
      was not significantly associated with DM (n = 13 studies; RR per 100 g/d = 1.12,
      95 % CI = 0.94, 1.34); nor were consumption of EPA+DHA (n = 16 cohorts; RR per
      250 mg/d = 1.04, 95 % CI = 0.97, 1.10) nor circulating levels of EPA+DHA
      biomarkers (n = 5 cohorts; RR per 3 % of total fatty acids = 0.94, 95 % CI =
      0.75, 1.17). Both dietary ALA (n = 7 studies; RR per 0.5 g/d = 0.93, 95 % CI =
      0.83, 1.04) and circulating ALA biomarker levels (n = 6 studies; RR per 0.1 % of
      total fatty acid = 0.90, 95 % CI = 0.80, 1.00, P = 0.06) were associated with non
      significant trend towards lower risk of DM. Substantial heterogeneity (I2~80 %)
      was observed among studies of fish/seafood or EPA+DHA and DM; moderate
      heterogeneity ( < 55 %) was seen for dietary and biomarker ALA and DM. In
      unadjusted meta-regressions, study location (Asia vs. North America/Europe), mean
      BMI, and duration of follow-up each modified the association between fish/seafood
      and EPA+DHA consumption and DM risk (P-interaction <= 0.02 each). We had limited
      statistical power to determine the independent effect of these sources of
      heterogeneity due to their high collinearity. The overall pooled findings do not
      support either major harms or benefits of fish/seafood or EPA+DHA on development
      of DM, and suggest that ALA may be associated with modestly lower risk. Reasons
      for potential heterogeneity of effects, which could include true biologic
      heterogeneity, publication bias, or chance, deserve further investigation.

PMID- 22591896
TI  - Omega-3 fatty acids and cancers: a systematic update review of epidemiological
      studies.
AB  - Experimental models showed consistently a modulation of carcinogenesis by omega 3
      polyunsaturated fatty acids (omega3 PUFA). Fish intake is often described as part
      of a beneficial dietary pattern. However, observational epidemiological studies
      on the relationship between omega3 PUFA reported conflicting results. The
      objective of this systematic review is to determine whether there exists any
      progress in the evaluation of the causal relationship between dietary omega3 PUFA
      and cancers since the previous FAO/OMS expert consultation and whether it is
      possible to propose preventive and/or adjuvant therapeutic recommendations.
      Prospective and case-control observational studies published since 2007 and
      meeting validity criteria were considered together with RCT. Experimental studies
      are mentioned to provide for biological plausibility. When evaluating the level
      of evidence, a portfolio approach was used, weighted by a hierarchy giving higher
      importance to prospective studies followed by RCT if any. There is a probable
      level of evidence that ALA per se is neither a risk factor nor a beneficial
      factor with regards to cancers. Observational studies on colorectal, prostate and
      breast cancers only provided limited evidence suggesting a possible role of LC
      omega3PUFA in cancer prevention because insufficient homogeneity of the
      observations. Explanation for heterogeneity might be the inherent difficulties
      associated with epidemiology (confounding and dietary pattern context,
      measurement error, level of intake, genetic polymorphism). The role of LC
      omega3PUFA as adjuvant, might be considered of possible use, in view of the
      latest RCT on lung cancers even if RCT on other cancers still need to be
      undertaken.

PMID- 22591897
TI  - Dietary sources of omega 3 fatty acids: public health risks and benefits.
AB  - Omega 3 fatty acids can be obtained from several sources, and should be added to
      the daily diet to enjoy a good health and to prevent many diseases. Worldwide,
      general population use omega-3 fatty acid supplements and enriched foods to get
      and maintain adequate amounts of these fatty acids. The aim of this paper was to
      review main scientific evidence regarding the public health risks and benefits of
      the dietary sources of omega-3 fatty acids. A systematic literature search was
      performed, and one hundred and forty-five articles were included in the results
      for their methodological quality. The literature described benefits and risks of
      algal, fish oil, plant, enriched dairy products, animal-derived food, krill oil,
      and seal oil omega-3 fatty acids.

PMID- 22591898
TI  - Omega-3 fatty acids and inflammatory bowel diseases - a systematic review.
AB  - BACKGROUND & AIM: Despite their well known anti-inflammatory actions, the
      clinical usefulness of omega-3 PUFA in inflammatory bowel disease is
      controversial. We aimed to systematically review the available data on the
      performance of omega-3 PUFA as therapeutic agents in these patients. METHODS:
      Electronic databases were systematically searched for RCT of fish oil or omega-3
      PUFA therapy in both active and inactive ulcerative colitis or Crohn's disease,
      without limitation on either the length of therapy or the form it was given,
      including nutritional supplements and enteral formula diets. Eligible articles
      were assessed for methodological quality on the basis of the adequacy of the
      randomisation process, concealment of allocation, blinding of intervention and
      outcome, possible biases, and completeness of follow-up. The five-point Oxford
      quality score was calculated. RESULTS: A total of 19 RCT were finally selected
      for this review. Overall, available data do not allow to support the use of omega
      3 PUFA supplementation for the treatment of both active and inactive inflammatory
      bowel disease. Negative results are quite consistent in trials assessing the use
      of omega-3 PUFA to maintain disease remission, particularly ulcerative colitis,
      and to a lesser extent Crohn's disease. Trials on their use in active disease do
      not allow to draw firm conclusions mainly because the heterogeneity of design
      (ulcerative colitis) or their short number (Crohn's disease). In most trials, the
      appropriateness of the selected placebo is questionable. CONCLUSION: The present
      systematic review does not allow to make firm recommendations about the
      usefulness of omega-3 PUFA in inflammatory bowel disease.

PMID- 22591900
TI  - Effects of omega 3 fatty acids supplementation in behavior and non
      neurodegenerative neuropsychiatric disorders.
AB  - This work provides a systematic review of all published randomised, controlled
      clinical trials (RCT) investigating the effects of n-3 PUFA intake on the
      prevention and treatment of non-neurodegenerative neuropsychiatric disorders.
      Five databases (PubMed, EMBASE, LILACS, CINAHL and The Cochrane Database) were
      searched for RCT in this area published up to April 2011. The selected studies
      all involved human participants and included a comparison group. Thirty eight
      studies were identified, which examined the influence of n-3 PUFA supplementation
      on the prevention/treatment of depression (non-perinatal) (n 23), perinatal
      depression (n 6) and attention deficit hyperactivity disorder (ADHD) (n 9). Great
      heterogeneity was noticed in terms of study design, the doses of n-3 PUFA
      administered, and study duration. Some benefit was noted with respect to the
      treatment of hyperactivity and depression in over half the examined studies,
      although the evidence was not conclusive. For any firm conclusions to be drawn,
      further studies will be needed that take into account the initial n-3 PUFA status
      of the subjects. Excessive n-3 PUFA intakes might be associated with a greater
      risk of peroxidation events and therefore neuropsychiatric deterioration. Indeed,
      some studies only recorded benefits when lower doses were administered. It is
      therefore important that the dose required to achieve any potential benefit be
      determined.

PMID- 22591899
TI  - A systematic review of omega-3 fatty acids and osteoporosis.
AB  - Some epidemiological evidence suggests that diets high in omega 3 fatty acids (n
      3 FAs) may be beneficial for skeletal health. The aim of this systematic review
      was to determine if randomized controlled trials (RCTs) support a positive effect
      of n-3 FAs on osteoporosis. A systematic search was performed in PubMed and
      EMBASE databases. We included RCTs with skeletal outcomes conducted in adults or
      children (> = 1 year old) using n-3 FA fortified foods, diets or supplements
      alone or in combination with other vitamins/minerals, versus placebo. Primary
      outcomes were incident fracture at any site and bone mineral density (BMD) in
      g/cm2. Secondary outcomes included bone formation or resorption markers and bone
      turnover regulators. A total of 10 RCTs met inclusion criteria. Effect sizes with
      95 % confidence intervals were estimated to compare studies across various
      treatments and outcome measures. No pooled analysis was completed due to
      heterogeneity of studies and small sample sizes. No RCTs included fracture as an
      outcome. Four studies reported significant favorable effects of n-3 FA on BMD or
      bone turnover markers. Of these, three delivered n-3 FA in combination with high
      calcium foods or supplements. Five studies reported no differences in outcomes
      between n-3 FA intervention and control groups; one study included insufficient
      data for effect size estimation. Strong conclusions regarding n-3 FAs and bone
      disease are limited due to the small number and modest sample sizes of RCTs,
      however, it appears that any potential benefit of n-3 FA on skeletal health may
      be enhanced by concurrent administration of calcium.

PMID- 22591902
TI  - Systematic reviews in nutrition: standardized methodology.
AB  - The objective of this study is to establish a methodological proposal in order to
      carry out qualitative systematic reviews and apply these findings to a review of
      Omega-3 Fatty Acids with respect to health and illness. Based on a methodological
      proposal, a general protocol was developed to provide a sound basis for the
      preparation of the reviews in this journal supplement. A systematic technique was
      proposed in order to revise the existing scientific literature on Omega-3 Fatty
      Acids, with particular emphasis on aspects relating to health and illness. The
      aim of qualitative systematic reviews is to collate and summarise the results of
      the primary studies reviewed which will be carried out through a descriptive
      synthesis. It can be concluded that systematic reviews provide a summary of the
      existing primary documents on a specific scientific question. The detailed and
      explicit methods used lead to the identification, critical evaluation and
      synthesis of the scientific literature. Furthermore, both bias and random effects
      are reduced, resulting in more reliable data from which to draw conclusions and
      make recommendations to support decision-making.

PMID- 22591901
TI  - Interactions between dietary n-3 fatty acids and genetic variants and risk of
      disease.
AB  - Nutritional genomics has undergone rapid development and the concept is now very
      popular with the general public. Therefore, there is increasing demand for
      knowledge on adapting dietary composition to the genome. Our aim has been to
      undertake a systematic review so as to find out the level of evidence existing on
      whether the effects of n-3 fatty acids on health can be modulated by genetic
      variation. A systematic literature search was conducted on studies that jointly
      analyse the effect of one or more genetic variants in candidate genes and n-3
      fatty acids. Both observational and experimental studies were included. Results
      are classified in accordance with whether the study was undertaken on
      intermediate phenotypes (plasma lipid concentrations, glucose, inflammation
      markers, anthropometric measurements) or disease phenotypes (cancer,
      cardiovascular diseases, metabolic syndrome, etc) and whether it was experimental
      or observational. A wide diversity of genetic variants and little consistency in
      the publication of replication studies was found. Greater consistency was
      observed in studies that involved the FADS1 and FADS2 locus in the determination
      of n-3 fatty acid concentrations in biological samples. Most of the studies were
      designed to measure gene-diet interactions and not diet-gene interactions.
      Despite the fact that multiple studies have shown statistically significant
      interactions between n-3 fatty acids and certain genetic variants on intermediate
      and disease phenotypes, the individual level of evidence is very low and
      recommendations cannot be made on increasing or reducing the intake of n-3 fatty
      acids based on each individual's genotype.

PMID- 22591903
TI  - Novel methodologies for assessing omega-3 fatty acid status - a systematic
      review.
AB  - Over the last few decades n-3 long chain polyunsaturated fatty acid status became
      of special interest for scientists. Biochemical measures on the n-3 fatty acid
      status vary depending on body compartment assessed and measures chosen. Plasma
      phospholipids and red blood cell membrane phospholipids are mainly used as n-3
      fatty acid status marker. The conventional analysis of phospholipid fatty acids
      involves lipid extraction and consecutive chromatographic separation of
      phospholipids from other lipid fractions, which is time-consuming and costly. In
      recent years, different investigators have tried to overcome these limitations by
      using other biological markers or by modifying the analytical procedures used to
      assess n-3 fatty acid status. The aim of this systematic review was to provide an
      overview on these novel analytical methods developed for the fatty acid
      quantification by gas chromatography, highlights the methodological limitations,
      and discusses advantages or disadvantages of the biological markers used.
      Seventeen papers were identified that fulfilled the inclusion criteria. New
      opportunities arise from sensitive and precise high-throughput methodologies for
      assessment of plasma total lipid and plasma glycerophospholipid fatty acids, as
      well as cheek cell fatty acid composition.

PMID- 22591904
TI  - Dietary methods and biomarkers of omega 3 fatty acids: a systematic review.
AB  - The aims of the present study were to review the validity of dietary methods used
      to measure the usual long chain (LC) omega-3 polyunsaturated fatty acid (n-3
      PUFA) intake of a population and to assess the usefulness of different biomarkers
      of n-3 PUFA in healthy humans. Two systematic literature searches were conducted
      until May 2011 to update previous systematic reviews. The first literature search
      aimed to find studies validating the methodology used for measuring the dietary
      intake of n-3 PUFA. The second search aimed to find human intervention studies in
      which n-3 PUFA status changed after 2 weeks of n-3 PUFA supplementation. Sixteen
      studies were identified for inclusion in the first review. Correlation
      coefficients between fatty acids in subcutaneous fat or blood lipids and dietary
      intake of n-3 PUFA from different questionnaires were similar. Subcutaneous fat
      has been reported as the best reference method for some authors, and these
      studies showed moderate correlation coefficients with no dietary intake method
      being superior to any other. As for the evaluation of biomarkers of
      docosahexaenoic acid (DHA, 22 : 6 n-3) and eicosapentaenoic acid (EPA, 20 : 5n-3)
      status in response to supplementation, the new search reaffirmed and reinforced
      the evidence supporting that plasma phospholipid DHA, erythrocyte DHA, and
      platelet DHA were all effective and robust biomarkers of DHA status. Our findings
      only confirmed earlier studies and did not provide evidence for reaching new
      conclusions.

PMID- 22591905
TI  - Omega 3 fatty acids, gestation and pregnancy outcomes.
AB  - Pregnancy is associated with a reduction in maternal serum docosahexaenoic acid
      (DHA, 22:6 n-3) percentage and its possible depletion in the maternal store.
      Since the synthesis of long chain polyunsaturated fatty acids (LCPUFA) in the
      fetus and placenta is low, both the maternal LCPUFA status and placental function
      are critical for their supply to the fetus. Maternal supplementation with DHA up
      to 1 g/d or 2.7 g n-3 LCPUFA did not have any harmful effect. DHA supplementation
      in large studies slightly the enhanced length of gestation (by about 2 days),
      which may increase the birth weight by about 50 g at delivery. However no advice
      can be given on their general using to avoid preterm deliveries in low or high
      risk pregnancies. Several studies, but not all, reported improvements of the
      offspring in some neurodevelopmental tests as a result of DHA supplementation
      during gestation, or, at least, positive relationships between maternal or cord
      serum DHA percentages and cognitive skills in young children. The effect seems
      more evident in children with low DHA proportions, which raises the question of
      how to identify those mothers who might have a poor DHA status and who could
      benefit from such supplementation. Most studies on the effects of n-3 LCPUFA
      supplementation during pregnancy on maternal depression were judged to be of low
      to-moderate quality, mainly due to small sample sizes and failure to adhere to
      Consolidated Standards of Reporting Trials guidelines. In contrast, the effects
      of n-3 LCPUFA supplementation on reducing allergic diseases in offspring are
      promising.

PMID- 22591906
TI  - Recommended dietary reference intakes, nutritional goals and dietary guidelines
      for fat and fatty acids: a systematic review.
AB  - Dietary fat and its effects on health and disease has attracted interest for
      research and Public Health. Since the 1980s many bodies and organizations have
      published recommendations regarding fat intake. In this paper different sets of
      recommendations are analyzed following a systematic review process to examine
      dietary reference intakes, nutritional goals and dietary guidelines for fat and
      fatty acids. A literature search was conducted in relevant literature databases
      along a search for suitable grey literature reports. Documents were included if
      they reported information on either recommended intake levels or dietary
      reference values or nutritional objectives or dietary guidelines regarding fat
      and/or fatty acids and/or cholesterol intake or if reported background
      information on the process followed to produce the recommendations. There is no
      standard approach for deriving nutrient recommendations. Recommendations vary
      between countries regarding the levels of intake advised, the process followed to
      set the recommendations. Recommendations on fat intake share similar figures
      regarding total fat intake, saturated fats and trans fats. Many sets do not
      include a recommendation about cholesterol intake. Most recent documents provide
      advice regarding specific n-3 fatty acids. Despite efforts to develop evidence
      based nutrient recommendations and dietary guidelines that may contribute to
      enhance health, there are still many gaps in research. It would be desirable that
      all bodies concerned remain transparent about the development of dietary
      recommendations. In order to achieve this, the type of evidence selected to base
      the recommendations should be specified and ranked. Regular updates of such
      recommendations should be planned.

PMID- 22591907
TI  - Omega 3 fatty acids on child growth, visual acuity and neurodevelopment.
AB  - The aim of this review is to evaluate the effects of omega-3 long chain
      polyunsaturated fatty acids (n-3 LCPUFA) supplementation in pregnant and
      lactating women and infants during postnatal life, on the visual acuity,
      psychomotor development, mental performance and growth of infants and children.
      Eighteen publications (11 sets of randomized control clinical trial [RCTs])
      assessed the effects of the n-3 LCPUFA supplementation during pregnancy on
      neurodevelopment and growth, in the same subjects at different time points; 4
      publications (2 data sets from RCTs) addressed physiological responses to n-3
      LCPUFA supplementation during pregnancy & lactation and 5 publications (3 data
      sets from RCTs) exclusively during lactation. Some of these studies showed
      beneficial effects of docosahexaenoic acid (DHA) supplementation during pregnancy
      and/or lactation especially on visual acuity outcomes and some on long-term
      neurodevelopment; a few, showed positive effects on growth. There were also 15
      RCTs involving term infants who received infant formula supplemented with DHA,
      which met our selection criteria. Many of these studies claimed a beneficial
      effect of such supplementation on visual, neural, or developmental outcomes and
      no effects on growth. Although new well designed and conducted studies are being
      published, evidence from RCTs does not demonstrate still a clear and consistent
      benefit of n-3 LCPUFA supplementation during pregnancy and/or lactation on term
      infants growth, neurodevelopment and visual acuity. These results should be
      interpreted with caution due to methodological limitations of the included
      studies.

PMID- 22591908
TI  - Telmisartan improves kidney function through inhibition of the oxidative
      phosphorylation pathway in diabetic rats.
AB  - Telmisartan provides renal benefit at all stages of the renal continuum in
      patients with type 2 diabetes mellitus. This research is to investigate the
      effect of telmisartan on kidney function in diabetic rats and to identify the
      underlying molecular mechanisms. Diabetic rats were divided into vehicle group,
      low dosage (TeL) group, and high dosage of telmisartan (TeH) group. We performed
      Illumina RatRef-12 Expression BeadChip gene array experiments. We found 3-months
      of treatment with telmisartan significantly decreased 24-h urinary albumin, serum
      creatinine, blood urea nitrogen, and increased creatinine clearance rate. Kidney
      hypertrophy and glomerular mesangial matrix expansion were ameliorated. The
      glomeruli from the TeH group had 1541 genes with significantly changed expression
      (554 increased, 987 decreased). DAVID (Database for annotation, visualization and
      Integrated discovery) analyses showed that the most enriched term was
      'mitochondrion' (Gene Ontology (GO:0005739)) in all 67 GO functional categories.
      Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that
      all differentially expressed genes included seven KEGG pathways. Of those
      pathways, four are closely related to the oxidative phosphorylation pathway.
      Quantitative real-time PCR verified that the H+ transporting mitochondrial F1
      complex, beta subunit (Atp5b), cytochrome c oxidase subunit VIc (Cox6c), and NADH
      dehydrogenase (ubiquinone) Fe-S protein 3 (Ndufs3) were significantly
      downregulated both in TeL and TeH groups, while nephrosis 1 homolog (Nphs1) and
      nephrosis 2 homolog (Nphs2) were significantly upregulated. The increased
      expression of malonaldehyde and NDUFS3 in the glomeruli of diabetic rats was
      attenuated by telmisartan. The other significantly changed pathway we found was
      the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Our data
      suggest that telmisartan can improve kidney function in diabetic rats. The
      mechanism may be involved in mitochondrion oxidative phosphorylation, the PPAR
      gamma pathway, and the slit diaphragm.

PMID- 22591909
TI  - Whole body diffusion for metastatic disease assessment in neuroendocrine
      carcinomas: comparison with OctreoScan(r) in two cases.
AB  - Neuroendocrine tumor (NET) patients must be adequately staged in order to improve
      a multidisciplinary approach and optimal management for metastatic disease.
      Currently available imaging studies include somatostatin receptor scintigraphy,
      like OctreoScan(r), computed tomography (CT), scans and magnetic resonance
      imaging (MRI), which analyze vascular concentration and intravenous contrast
      enhancement for anatomic tumor localization. However, these techniques require
      high degree of expertise for interpretation and are limited by their
      availability, cost, reproducibility, and follow-up imaging comparisons. NETs
      significantly reduce water diffusion as compared to normal tissue. Diffusion
      weighted imaging (DWI) in MRI has an advantageous contrast difference: the tumor
      is represented with high signal over a black normal surrounding background. The
      whole-body diffusion (WBD) technique has been suggested to be a useful test for
      detecting metastasis from various anatomic sites. In this article we report the
      use of DWI in MRI and WBD in two cases of metastatic pulmonary NET staging in
      comparison with OctreoScan(r) in order to illustrate the potential advantage of
      DWI and WBD in staging NETs.

PMID- 22591910
TI  - Striatal dopamine D2/3 receptor binding following dopamine depletion in subjects
      at Ultra High Risk for psychosis.
AB  - Altered striatal dopaminergic neurotransmission is thought to be fundamental to
      schizophrenia. Increased presynaptic dopaminergic activity ([18F]-DOPA PET) may
      predate the onset of psychotic symptoms and correlates to clinical symptoms in
      subjects at Ultra High Risk (UHR) for developing psychosis. Postsynaptic
      dopaminergic neurotransmission has not been investigated yet in UHR patients. We
      hypothesized that synaptic dopamine concentration would be increased in UHR
      patients, and that synaptic dopamine concentration would be related to symptom
      severity. 14 UHR patients and 15 age and IQ matched controls completed an [123I]
      IBZM SPECT scan at baseline and again after dopamine depletion with alpha-methyl
      para-tyrosine (AMPT). We measured changes in radiotracer binding potential,
      compared these between UHR patients and controls, and correlated these to symptom
      severity. The UHR group as a whole did not differ significantly from controls.
      AMPT significantly reduced symptom severity in the UHR group (p=0.014). Higher
      synaptic dopamine concentration predicted larger reduction of positive symptoms
      following depletion in the UHR group (p=0.01). In UHR patients, positive symptoms
      responded to dopamine depletion, comparable to observations in schizophrenia,
      suggesting a similar mechanism. Higher synaptic dopamine concentration was
      associated with more severe positive symptoms and a greater reduction of these
      symptoms following depletion.

PMID- 22591911
TI  - Chronic effects of corticosterone on GIRK1-3 subunits and 5-HT1A receptor
      expression in rat brain and their reversal by concurrent fluoxetine treatment.
AB  - Dysregulation of the serotonergic system and abnormalities of the hypothalamic
      pituitary-adrenal axis have been demonstrated in major depression. Animal studies
      indicate that 5-HT1A receptor expression may be reduced by long-term
      administration of corticosterone. However, similar studies on the regulation of
      GIRK channels, one of the most important effectors of the neuronal 5-HT1A
      receptor, are limited. In order to address these issues, slow-release
      corticosterone pellets were implanted subcutaneously to adrenal intact male rats
      (200mg pellets, 35 days release). Starting on day 15, animals were treated for 21
      days with fluoxetine (5mg/kg/day, i.p.), or vehicle. Using in situ hybridization
      histochemistry and receptor autoradiography, we found that chronic corticosterone
      treatment was accompanied by a significant decrease on the mRNAs coding for
      mineralocorticoid receptors in hippocampal areas. Under these conditions, 5-HT1A
      receptor mRNA expression decreased in dorsal raphe nucleus and dentate gyrus.
      However, 5-HT1A receptor levels, as measured by [(3)H]-8-OH-DPAT binding,
      diminished significantly only in dentate gyrus. It is noteworthy that chronic
      treatment with fluoxetine reversed the alterations on 5-HT1A receptor mRNA levels
      only in dorsal raphe. Finally, chronic corticosterone treatment produced an
      increase on the mRNA coding for the GIRK2 subunit in several hypothalamic and
      thalamic areas, which was reversed by fluoxetine. Measurements of cell density
      and volume of the granular layer of the dentate gyrus did not reveal significant
      changes after corticosterone or corticosterone plus fluoxetine treatments. These
      data are relevant for a better understanding of the differential regulation of
      pre- and postsynaptic 5-HT1A receptors by corticosterone flattened rhythm.

PMID- 22591912
TI  - Concordance between whole-slide imaging and light microscopy for routine surgical
      pathology.
AB  - The use of high-resolution digital images of histopathology slides as a routine
      diagnostic tool for surgical pathology was investigated. The study purpose was to
      determine the diagnostic concordance between pathologic interpretations using
      whole-slide imaging and standard light microscopy. Two hundred fifty-one
      consecutive surgical pathology cases (312 parts, 1085 slides) from a single
      pathology service were included in the study after cases had been signed out and
      reports generated. A broad array of diagnostic challenges and tissue sources were
      represented, including 52 neoplastic cases. All cases were digitized at *20 and
      presented to 2 pathologists for diagnosis using whole-slide imaging as the sole
      diagnostic tool. Diagnoses rendered by the whole-slide imaging pathologists were
      compared with the original light microscopy diagnoses. Overall concordance
      between whole-slide imaging and light microscopy as determined by a third
      pathologist and jury panel was 96.5% (95% confidence interval, 94.8%-98.3%).
      Concordance between whole-slide imaging pathologists was 97.7% (95% confidence
      interval, 94.7%-99.2%). Five cases were discordant between the whole-slide
      imaging diagnosis and the original light microscopy diagnosis, of which 2 were
      clinically significant. Discordance resulted from interpretive criteria or
      diagnostic error. The whole-slide imaging modality did not contribute to
      diagnostic differences. Problems encountered by the whole-slide imaging
      pathologists primarily involved the inability to clearly visualize nuclear detail
      or microscopic organisms. Technical difficulties associated with image scanning
      required at least 1 slide be rescanned in 13% of the cases. Technical and
      operational issues associated with whole-slide imaging scanning devices used in
      this study were found to be the most significant obstacle to the use of whole
      slide imaging in general surgical pathology.

PMID- 22591913
TI  - Tissue-based predictors of germ-line BRCA1 mutations: implications for triaging
      of genetic testing.
AB  - BRCA testing of patients with breast cancer considered at high risk for having a
      germ-line BRCA mutation usually consists of comprehensive mutational analysis of
      both BRCA1 and BRCA2. A more cost-effective strategy of triaging patients for
      analysis of a single gene could be adopted if tissue-based predictors indicated a
      high risk specifically for either BRCA1 or BRCA2. To identify potentially useful
      tissue-based predictors of BRCA mutation status in breast cancer, we evaluated
      multiple histopathologic features of invasive breast carcinoma on archival tissue
      sections from 196 high-risk patients who had undergone BRCA testing, and we
      analyzed which individual or combination of features was most associated with
      BRCA mutations. Of the 196 patients with invasive breast carcinoma, there were 44
      (22%) with a deleterious BRCA1 mutation and 27 (14%) with a deleterious BRCA2
      mutation. For patients with available untreated surgical resection specimens for
      evaluation (n=172), estrogen receptor-positive phenotype was inversely associated
      with the presence of a BRCA1 mutation (odds ratio, 0.243; 95% confidence
      interval, 0.070-0.840; P=.025), and high mitotic activity (>=25 mitotic figures
      per 10 high-power fields) was directly associated with the presence of a BRCA1
      mutation (odds ratio, 4.222; 95% confidence interval, 1.353-13.18; P=.013). The
      combination of estrogen receptor-negative phenotype and high mitotic rate had
      high specificity (99%; 95% confidence interval, 95%-100%) but low sensitivity
      (43%; 95% confidence interval, 26%-61%) for identifying a deleterious BRCA1
      mutation. In patients with breast cancer at high risk for carrying a BRCA
      mutation, those with estrogen receptor-negative phenotype and high mitotic rate
      could be triaged specifically for BRCA1 testing instead of initially performing
      mutational analysis for both BRCA1 and BRCA2.

PMID- 22591914
TI  - Simultaneous extraction and determination of HBCD isomers and TBBPA by ASE and LC
      MSMS in fish.
AB  - Since the EFSA enquired a call for data for TBBPA and HBCD in 2009, the
      analytical determination of these compounds in food became of regulatory
      interest. Therefore, a method for the simultaneous determination of TBBPA and the
      three major HBCD stereoisomers was developed. Conventional techniques like
      soxhlet, ASE, GPC, sulphuric acid digestion, and acidified silica SPE are
      generally used in sample pre-treatment while detection is mostly performed by LC
      MSMS. A combined analysis of HBCD and TBBPA is problematic due to the hydroxyl
      groups in the TBBPA molecule. However, using a specific mesh-size sodium sulphate
      in ASE extraction and an acid silica column combined with a Sep-pack Plus silica
      cartridge for purification resulted in recoveries between 80% and 110% for all
      compounds. The accuracy and reproducibility determined using proficiency test
      samples were 104% and 4% for the sum of the HBCD isomers. Typical limits of
      detection were 0.01 ng/g product or 0.004 ng on column, while the linear dynamic
      range is between 0.01 ng and 10 ng on column. Levels of TBBPA and HBCD isomers
      were determined in eel samples. TBBPA was occasionally detected and only
      marginally above the quantification limit of 0.05 ng/g, whereas total amounts of
      HBCD were between 0.2 and 150 ng/g with alpha-HBCD being the dominant HBCD
      isomer.

PMID- 22591915
TI  - [18F]desmethoxyfallypride as a novel PET radiotracer for quantitative in vivo
      dopamine D2/D3 receptor imaging in rat models of neurodegenerative diseases.
AB  - INTRODUCTION: [(18)F]desmethoxyfallypride ([(18)F]DMFP) is a promising tracer for
      longitudinal assessment of striatal dopamine D2/D3-receptor (D2R) availability by
      positron emission tomography (PET) in small animal models. We explored the
      feasibility of [(18)F]DMFP-PET to image D2R availability in rat models of
      Huntington's (HD) and Parkinson's disease (PD). METHODS: Animals received either
      unilateral intrastriatal quinolinic acid lesions or medial forebrain bundle
      injections of 6-OHDA to produce the loss of striatal projection neurones or
      deplete the striatal dopamine, corresponding to established animal models for HD
      and PD, respectively. Three weeks after lesioning, PET scans were acquired on a
      microPET Focus 120 system following the tail vein injection of [(18)F]DMFP.
      RESULTS: [(18)F]DMFP-PET clearly visualized lesion induced decreases and
      increases of D2R availability. In vivo estimates of D2R binding and changes
      thereof gained by pharmacokinetic analyses correlated significantly with D2R
      density and its change provided by in vitro [(3)H]raclopride-autoradiography.
      CONCLUSIONS: In conclusion, [(18)F]DMFP-PET is a suitable method for in vivo D2R
      assessment in preclinical research, e.g for monitoring cell-based therapies.

PMID- 22591916
TI  - Performance of non-neurological older adults on the Wisconsin Card Sorting Test
      and the Stroop Color-Word Test: normal variability or cognitive impairment?
AB  - There is currently no standard criterion for determining abnormal test scores in
      neuropsychology; thus, a number of different criteria are commonly used. We
      investigated base rates of abnormal scores in healthy older adults using raw and
      T-scores from indices of the Wisconsin Card Sorting Test and Stroop Color-Word
      Test. Abnormal scores were examined cumulatively at seven cutoffs including >1.0,
      >1.5, >2.0, >2.5, and >3.0 standard deviations (SD) from the mean as well as
      those below the 10th and 5th percentiles. In addition, the number of abnormal
      scores at each of the seven cutoffs was also examined. Results showed when
      considering raw scores, ~15% of individuals obtained scores>1.0 SD from the mean,
      around 10% were less than the 10th percentile, and 5% fell >1.5 SD or <5th
      percentile from the mean. Using T-scores, approximately 15%-20% and 5%-10% of
      scores were >1.0 and >1.5 SD from the mean, respectively. Roughly 15% and 5% fell
      at the <10th and <5th percentiles, respectively. Both raw and T-scores>2.0 SD
      from the mean were infrequent. Although the presence of a single abnormal score
      at 1.0 and 1.5 SD from the mean or at the 10th and 5th percentiles was not
      unusual, the presence of >=2 abnormal scores using any criteria was uncommon.
      Consideration of base rate data regarding the percentage of healthy individuals
      scoring in the abnormal range should help avoid classifying normal variability as
      neuropsychological impairment.

PMID- 22591917
TI  - Brain antioxidant markers, cognitive performance and acetylcholinesterase
      activity of rats: efficiency of Sonchus asper.
AB  - BACKGROUND: Sonchus asper (SA) is traditionally used as a folk medicine to treat
      mental disorders in Pakistan. The aim of this study was to investigate the effect
      of polyphenolic rich methanolic fraction of SA on cognitive performance, brain
      antioxidant activities and acetylcholinesterase activity in male rats. METHODS:
      30 male Sprague-Dawley rats were equally divided into three groups in this study.
      Animals of group I (control) received saline (vehicle), group II received SA (50
      mg/kg) body weight (b.w.), and group III treated with SA (100 mg/kg b.w.,) orally
      in dimethyl sulphoxide (DMSO) for 7 days. The effect of SA was checked on rat
      cognitive performance, brain antioxidatant and acetylcholinesterase activities.
      Evaluation of learning and memory was assessed by a step-through a passive
      avoidance test on day 6 after two habituation trials and an initial acquisition
      trial on day 5. Antioxidant potential was determined by measuring activities of
      superoxide dismutase (SOD), catalase (CAT), contents of thiobarbituric acid
      reactive substances (TBARS) and reduced glutathione (GSH) in whole-brain
      homogenates. Acetylcholinesterase (AChE) activity was determined by the
      colorimetric method. RESULTS: Results showed that 100 mg/kg b.w., SA treated rats
      exhibited a significant improvement in learning and memory (step-through latency
      time). SA administration reduced lipid peroxidation products and elevated
      glutathione levels in the SA100-treated group. Furthermore, salt and detergent
      soluble AChE activity was significantly decreased in both SA-treated groups.
      Short-term orally supplementation of SA showed significant cognitive enhancement
      as well as elevated brain antioxidant enzymes and inhibited AChE activity.
      CONCLUSION: These findings stress the critical impact of Sonchus asper bioactive
      components on brain function.

PMID- 22591918
TI  - Confocal laser scanning microscopy analysis of S. epidermidis biofilms exposed to
      farnesol, vancomycin and rifampicin.
AB  - BACKGROUND: Staphylococcus epidermidis is the major bacterial species found in
      biofilm-related infections on indwelling medical devices. Microbial biofilms are
      communities of bacteria adhered to a surface and surrounded by an extracellular
      polymeric matrix. Biofilms have been associated with increased antibiotic
      tolerance to the immune system. This increased resistance to conventional
      antibiotic therapy has lead to the search for new antimicrobial therapeutical
      agents. Farnesol, a quorum-sensing molecule in Candida albicans, has been
      described as impairing growth of several different microorganisms and we have
      previously shown its potential as an adjuvant in antimicrobial therapy against S.
      epidermidis. However, its mechanism of action in S. epidermidis is not fully
      known. In this work we better elucidate the role of farnesol against S:
      epidermidis biofilms using confocal laser scanning microscopy (CLSM). FINDINGS:
      24 h biofilms were exposed to farnesol, vancomycin or rifampicin and were
      analysed by CLSM, after stained with a Live/Dead stain, a known indicator of cell
      viability, related with cell membrane integrity. Biofilms were also disrupted by
      sonication and viable and cultivable cells were quantified by colony forming
      units (CFU) plating. Farnesol showed a similar effect as vancomycin, both causing
      little reduction of cell viability but at the same time inducing significant
      changes in the biofilm structure. On the other hand, rifampicin showed a distinct
      action in S. epidermidis biofilms, by killing a significant proportion of biofilm
      bacteria. CONCLUSIONS: While farnesol is not very efficient at killing biofilm
      bacteria, it damages cell membrane, as determined by the live/dead staining, in a
      similar way as vancomycin. Furthermore, farnesol might induce biofilm detachment,
      as determined by the reduced biofilm biomass, which can partially explain the
      previous findings regarding its role as a possible chemotherapy adjuvant.

PMID- 22591919
TI  - Hepatic arterial reconstruction for orthotopic liver transplantation in the rat.
AB  - BACKGROUND: Orthotopic liver transplantation (OLT) models in rats have been
      investigated in many studies. The reconstruction of hepatic artery is required
      for reliable OLT and also requires advanced skills. METHODS: The hepatic artery
      reconstructions by a hand-suture technique and a new method using a micro T-tube
      were investigated in rats with a whole-liver syngeneic graft. Operative time and
      postoperative patency were compared between the hand-suture and micro T-tube
      techniques. RESULTS: Our technique using the micro T-tube shortened the operative
      time of recipient surgery compared with the hand-suture technique and prolonged
      the operative time for the donor. The patency ratio was maintained at 24h after
      OLT with hand suturing but was significantly reduced with the micro T-tube, which
      had a patency ratio of 0.83 only up to 6h after OLT. CONCLUSION: The micro T-tube
      technique may have potential usefulness in the rat OLT model but requires further
      modification.

PMID- 22591920
TI  - Minocycline ameliorates lung and liver dysfunction in a rodent model of
      hemorrhagic shock/resuscitation plus abdominal compartment syndrome.
AB  - BACKGROUND: We sought to elucidate whether minocycline, a broad-spectrum
      tetracycline antibiotic with potent anti-inflammation capacity, could mitigate
      inflammatory response and organ dysfunction in the lungs and liver induced by
      hemorrhagic shock/resuscitation (HS) plus abdominal compartment syndrome (ACS).
      MATERIALS AND METHODS: Adult male rats were randomized to receive HS plus ACS or
      HS plus ACS plus minocycline (denoted as the HS/A and HS/A-M group, respectively;
      n = 12). Sham-instrumentation groups were employed to serve as the controls.
      Hemorrhagic shock/resuscitation was induced by blood drawing (mean arterial
      pressure: 40-45 mm Hg for 60 min) followed by shed blood/saline mixture
      reinfusion. Subsequently, intra-abdominal pressure (IAP) was increased to 25 mm
      Hg by injecting air into the preplaced intraperitoneal latex balloon to induce
      ACS. Minocycline (20 mg/kg) was intravenously administered immediately after
      resuscitation. IAP was maintained at 25 mm Hg for 6 h. Then, all rats were
      euthanized. RESULTS: The levels of polymorphonuclear leukocyte infiltration, the
      wet/dry weight ratio, and the concentrations of inflammatory molecules (e.g.,
      chemokine, cytokine, and prostaglandin E2) in lung and liver tissues of the HS/A
      group were significantly higher than those of the HS/A-M groups (all P < 0.05).
      Moreover, the levels of lung dysfunction (assayed by arterial blood gas) and
      liver dysfunction (assayed by plasma concentrations of bilirubin, aspartate
      aminotransferase, and alaninine aminotransferase) of the HS/A group were
      significantly higher than those of the HS/A-M group (all P < 0.05). CONCLUSIONS:
      Minocycline ameliorates inflammatory response and organ dysfunction in the lungs
      and liver induced by hemorrhagic shock/resuscitation plus abdominal compartment
      syndrome.

PMID- 22591921
TI  - Aortic balloon occlusion is effective in controlling pelvic hemorrhage.
AB  - BACKGROUND: The objective of this study was to evaluate the efficacy of
      resuscitative endovascular aortic balloon occlusion (REBOA) of the distal aorta
      in a porcine model of pelvic hemorrhage. METHODS: Swine were entered into three
      phases of study: injury (iliac artery), hemorrhage (45 s), and intervention (180
      min). Three groups were studied: no intervention (NI, n = 7), a kaolin
      impregnated gauze (Combat Gauze) (CG, n = 7), or REBOA (n = 7). The protocol was
      repeated with a dilutional coagulopathy (CG-C, n = 7, and REBOA-C, n = 7).
      Measures of physiology, rates of hemorrhage, and mortality were recorded.
      RESULTS: Rate of hemorrhage was greatest in the NI group, followed by the REBOA
      and CG groups (822 +/- 415 mL/min versus 11 +/- 13 and 0.2 +/- 0.4 mL/min
      respectively; P < 0.001). MAP following intervention (at 15 min) was the same in
      the CG and REBOA groups and higher than in the NI group (70 +/- 4 and 70 +/- 11
      mm Hg versus 5 +/- 13 mm Hg respectively; P < 0.001). There was 100% mortality in
      the NI group, with no deaths in the CG or REBOA group. In the setting of
      coagulopathy, the rate of bleeding was higher in the CG-C versus the REBOA-C
      group (229 +/- 295 mL/min versus 20 +/- 7 mL/min, P = 0.085). MAP following
      intervention (15 min) was higher in the REBOA-C than the CG-C group (71 +/- 12 mm
      Hg versus 28 +/- 31 mm Hg; P = 0.005). There were 5 deaths (71.4%) in the CG-C
      group, but none in the REBOA-C group (P = 0.010). CONCLUSION: Balloon occlusion
      of the aorta is an effective method to control pelvic arterial hemorrhage. This
      technique should be further developed as an adjunct to manage noncompressible
      pelvic hemorrhage.

PMID- 22591922
TI  - Deconstructing intraoperative communication failures.
AB  - BACKGROUND: Communication failure is a common contributor to adverse events. We
      sought to characterize communication failures during complex operations. METHODS:
      We video recorded and transcribed six complex operations, representing 22 h of
      patient care. For each communication event, we determined the participants and
      the content discussed. Failures were classified into four types: audience (key
      individuals missing), purpose (issue nonresolution), content
      (insufficient/inaccurate information), and/or occasion (futile timing). We added
      a systems category to reflect communication occurring at the organizational
      level. The impact of each identified failure was described. RESULTS: We observed
      communication failures in every case (mean 29, median 28, range 13-48), at a rate
      of one every 8 min. Cross-disciplinary exchanges resulted in failure nearly twice
      as often as intradisciplinary ones. Discussions about or mandated by hospital
      policy (20%), personnel (18%), or other patient care (17%) were most error prone.
      Audience and purpose each accounted for >40% of failures. A substantial
      proportion (26%) reflected flawed systems for communication, particularly those
      for disseminating policy (29% of system failures), coordinating personnel (27%),
      and conveying the procedure planned (27%) or the equipment needed (24%). In 81%
      of failures, inefficiency (extraneous discussion and/or work) resulted. Resource
      waste (19%) and work-arounds (13%) also were frequently seen. CONCLUSIONS: During
      complex operations, communication failures occur frequently and lead to
      inefficiency. Prevention may be achieved by improving synchronous, cross
      disciplinary communication. The rate of failure during discussions about/mandated
      by policy highlights the need for carefully designed standardized interventions.
      System-level support for asynchronous perioperative communication may streamline
      operating room coordination and preparation efforts.

PMID- 22591923
TI  - Gastrointestinal disease outbreaks in cycling events: are preventive measures
      effective?
AB  - In 2009, following a bike race, a gastrointestinal illness outbreak affected many
      participants. A cohort study showed an attack rate of 16.3% with the main risk
      factor being mud splashes to the face. Considering these findings, in 2010
      recommendations to participants in the bike race were issued and environmental
      control measures were implemented. In 2010, a retrospective cohort study using
      web-based questionnaires was conducted to measure the use of preventive measures
      and to assess risk factors associated with gastrointestinal illness. A 69%
      response rate was achieved and 11721 records analysed, with 572 (attack rate
      4.9%) matching the case definition, i.e. participants reporting diarrhoea within
      10 days of race. There was a clear increase in the use of mudguards (96.7%
      reported access to/receiving information on preventive measures) and a
      significant decrease in gastrointestinal illness. This may indicate that the
      measures have been effective and should be considered, both in terms of
      environmental control measures as well as individual measures.

PMID- 22591924
TI  - Analysis of trends and emergency activities relating to critical victims of the
      Chuetsuoki Earthquake.
AB  - INTRODUCTION: When a large-scale disaster occurs, it is necessary to use the
      available resources in a variety of sites and scenes as efficiently as possible.
      To conduct such operations efficiently, it is necessary to deploy limited
      resources to the places where they will be the most effective. In this study,
      emergency and medical response activities that occurred following the Chuetsuoki
      Earthquake in Japan were analyzed to assess the most efficient and effective
      activities. METHODS: Records of patient transports by emergency services relating
      to the Niigata Chuetsuoki Earthquake, a magnitude 6.8 earthquake that struck
      Japan on 16 July 2007 were analyzed, and interview surveys were conducted.
      RESULTS: The occurrence of serious injuries caused by this earthquake essentially
      was limited to the day the earthquake struck. A total of 682 patients were
      treated on the day of the quake, of which about 90 were hospitalized. Of the 17
      patients whose conditions were life-threatening, three were rescued and
      transported to hospital by firefighters, three were transported by ambulance, and
      11 were transported to hospital using private means. Sixteen people were
      subsequently transferred to other hospitals, six of these by helicopter. There
      was difficulty in meeting all of the requests for emergency services within 4 to
      6 hours of the earthquake's occurrence. Most transports of patients whose
      conditions were life-threatening were between hospitals rather than from the
      scene of the injury. Transfers of critical patients between hospitals were
      efficient early on, but this does not necessarily mean that inter-hospital
      transfers were given higher priority than treatment at emergency scenes.
      CONCLUSION: During the acute emergency period following a disaster-causing event,
      it is difficult to meet all requests for emergency services. In such cases, it is
      necessary to conduct efficient activities that target critically injured
      patients. Since hospital transfers are matters of great urgency, it is necessary
      to consider assigning resource investment priority to hospital transfers during
      this acute period, when ambulance services may be insufficient to meet all needs.
      To deal with such disasters appropriately, it is necessary to ensure effective
      information exchange and close collaboration between ambulance services,
      firefighting organizations, disaster medical assistance teams, and medical
      institutions.

PMID- 22591925
TI  - Celebrating the end of school life: a pilot study.
AB  - INTRODUCTION: Celebrating the end of secondary schooling ("Schoolies Festival")
      is an established part of the school culture in Australia, with thousands of
      young students converging at beachside locations to celebrate this rite of
      passage. The aim of this study was to identify what young people believe is
      important to remain safe and healthy at this mass-gathering event. METHODS: This
      study was conducted using postcard surveys requesting demographic data and
      responses to the questions: (1) What do you think is important to stay safe and
      healthy at this event?; (2) What do you think is risky attending this event?; (3)
      Which of these is most likely to affect you at this event?; and (4) Where would
      you seek medical support? The surveys were distributed to attendees of a
      "Schoolies Festival" in Adelaide, Australia in 2008. RESULTS: One hundred sixty
      five of the 300 postcards were returned completed. The average age of the
      respondents was 17.7 years. "Not using drugs" was considered important to staying
      safe and healthy by 120 (73%) of respondents; "drinking alcohol responsibly" was
      considered important by 89 (54%); and "violent behavior" and "exposure to illicit
      drugs" were identified as important risks by 135 (82%) and 98 (59%) of
      participants, respectively. Only 35 (21%) of respondents indicated that they
      would seek on-site health care if needed. CONCLUSION: Young people attending mass
      gathering celebrations have valid concerns about drinking responsibly, exposure
      to illicit drugs, and sexual harassment. Health messages or health promotion
      strategies aimed at their specific concerns would be helpful in the mitigation of
      illness or injury at such events.

PMID- 22591926
TI  - The evaluation of research methods during disaster exercises: applicability for
      improving disaster health management.
AB  - INTRODUCTION: The objective of this study was to investigate whether disaster
      exercises can be used as a proxy environment to evaluate potential research
      instruments designed to study the application of medical care management
      resources during a disaster. METHODS: During an 06 April 2005 Ministerial-level
      exercise in the Netherlands, three functional areas of patient contact were
      assessed: (1) Command and Control, through the application of an existing
      incident management system questionnaire; (2) patient flow and quality of patient
      distribution, through registration of data from prehospital casualty collection
      points, ambulances, and participating trauma centers (with inclusion of data in a
      flow chart); and (3) hospital coping capacity, through timed registration reports
      from participating trauma centers. RESULTS: The existing incident management
      system questionnaire used for evaluating Command and Control during a disaster
      exercise would benefit from minor adaptations and validation that could not be
      anticipated in the exercise planning stage. Patient flow and the quality of
      patient distribution could not be studied during the exercise because of
      inconsistencies among data, and lack of data from various collection points.
      Coping capacity was better measured by using 10-minute rather than one hour time
      intervals, but provided little information regarding bottlenecks in surge
      capacity. CONCLUSION: Research instruments can be evaluated and improved when
      tested during a disaster exercise. Lack of data recovery hampers disaster
      research even in the artificial setting of a national disaster exercise.
      Providers at every level must be aware that proper data collection is essential
      to improve the quality of health care during a disaster, and that predisaster
      cooperation is crucial to validate patient outcomes. These problems must be
      addressed pre-exercise by stakeholders and decision-makers during planning,
      education, and training. If not, disaster exercises will not meet their full
      potential.

PMID- 22591927
TI  - Student perception of high fidelity medical simulation for an international
      trauma life support course.
AB  - BACKGROUND: High fidelity medical simulators (HFMS) are accepted tools for health
      care instruction. The use of HFMS was incorporated into an International Trauma
      Life Support course, and course participants were surveyed regarding attitudes
      toward HFMS. METHODS: Course participants, including physicians, nurses, and
      prehospital personnel, were given pre- and post-course questionnaires measuring
      their confidence in knowledge and treatment of trauma resuscitation, as well as
      their attitudes towards the utility and realism of immersive simulation. The
      participants were randomly assigned to take a course examination either before or
      after their simulator session. RESULTS: Thirteen course participants of varying
      backgrounds and degrees of clinical experience were surveyed and tested. All
      surveyed areas improved following simulator training, including comfort level
      with simulation as a training method (17%), perception of the realism of HFMS
      (15%), and reported self-confidence in knowledge, experience and training in
      trauma care (27%). Test scores were improved in the post-simulation group as
      opposed to the pre-simulation group (86% pass rate in the post-simulation test
      group versus 50% pass rate in the pre-simulation test group). CONCLUSIONS: High
      fidelity medical simulation was accepted by medical professionals of different
      backgrounds and experience. Attitudes towards simulation and self-confidence
      improved after simulator sessions, as did test scores, suggesting improved
      comprehension and retention of course materials. Further testing is required to
      validate the findings of this small, observational study.

PMID- 22591928
TI  - Increasing emergency medicine residents' confidence in disaster management: use
      of an emergency department simulator and an expedited curriculum.
AB  - INTRODUCTION: Disaster Medicine is an increasingly important part of medicine.
      Emergency Medicine residency programs have very high curriculum commitments, and
      adding Disaster Medicine training to this busy schedule can be difficult.
      Development of a short Disaster Medicine curriculum that is effective and
      enjoyable for the participants may be a valuable addition to Emergency Medicine
      residency training. METHODS: A simulation-based curriculum was developed. The
      curriculum included four group exercises in which the participants developed a
      disaster plan for a simulated hospital. This was followed by a disaster
      simulation using the Disastermed.Ca Emergency Disaster Simulator computer
      software Version 3.5.2 (Disastermed.Ca, Edmonton, Alberta, Canada) and the
      disaster plan developed by the participants. Progress was assessed by a pre- and
      post-test, resident evaluations, faculty evaluation of Command and Control, and
      markers obtained from the Disastermed.Ca software. RESULTS: Twenty-five residents
      agreed to partake in the training curriculum. Seventeen completed the simulation.
      There was no statistically significant difference in pre- and post-test scores.
      Residents indicated that they felt the curriculum had been useful, and judged it
      to be preferable to a didactic curriculum. In addition, the residents' confidence
      in their ability to manage a disaster increased on both a personal and and a
      departmental level. CONCLUSIONS: A simulation-based model of Disaster Medicine
      training, requiring approximately eight hours of classroom time, was judged by
      Emergency Medicine residents to be a valuable component of their medical
      training, and increased their confidence in personal and departmental disaster
      management capabilities.

PMID- 22591929
TI  - Prehospital trauma system reduces mortality in severe trauma: a controlled study
      of road traffic casualties in Iraq.
AB  - INTRODUCTION: In low-resource communities with long prehospital transport times,
      most trauma deaths occur outside the hospital. Previous studies from Iraq
      demonstrate that a two-tier network of rural paramedics with village-based first
      helpers reduces mortality in land mine and war-injured from 40% to 10%. However,
      these studies of prehospital trauma care in low-income countries have been
      conducted with historical controls, thus the results may be unreliable due to
      differences in study contexts. The aim of this study was to use a controlled
      study design to examine the effect of a two-tier prehospital rural trauma system
      on road traffic accident trauma mortality. METHODS: A single referral surgical
      hospital was the endpoint in a single-blinded, non-randomized cohort study. The
      catchment areas consisted of some districts with no formal Emergency Medical
      Services (EMS) system, and other districts where 95 health center paramedics had
      been trained and equipped to provide advanced life support, and 5,000 laypersons
      had been trained to give on-site first aid. The hospital staff registered trauma
      mortality and on-admission physiological severity blindly. Assuming that
      prehospital care would have no significant impact on mortality in moderate
      injuries, only road traffic accident (RTA) casualties with an Injury Severity
      Score (ISS)>=9 were selected for study. RESULTS: During a three-month study
      period, 205 patients were selected for study (128 in the treatment group and 77
      in the control group). The mean prehospital transit time was approximately two
      hours. The two groups were comparable with regards to demographic
      characteristics, distribution of wounds and injuries, and mean anatomical
      severity. The mortality rate was eight percent in the treatment group, compared
      to 44% in the control group (95% CI, 25%-48%). Adjusted for severity differences
      between the treatment and control groups, prehospital care was a significant
      contributor to survival. CONCLUSION: Where prehospital transport time is long, a
      two-tier prehospital system of trained paramedics and layperson first responders
      reduces trauma mortality in severe RTA injuries. The findings may be valid for
      civilian Emergency Medical Services interventions in other low-resource
      countries.

PMID- 22591930
TI  - Balancing between closeness and distance: emergency medical services personnel's
      experiences of caring for families at out-of-hospital cardiac arrest and sudden
      death.
AB  - INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) is a lethal health problem
      that affects between 236,000 and 325,000 people in the United States each year.
      As resuscitation attempts are unsuccessful in 70-98% of OHCA cases, Emergency
      Medical Services (EMS) personnel often face the needs of bereaved family members.
      PROBLEM: Decisions to continue or terminate resuscitation at OHCA are influenced
      by factors other than patient clinical characteristics, such as EMS personnel's
      knowledge, attitudes, and beliefs regarding family emotional preparedness.
      However, there is little research exploring how EMS personnel care for bereaved
      family members, or how they are affected by family dynamics and the emotional
      contexts. The aim of this study is to analyze EMS personnel's experiences of
      caring for families when patients suffer cardiac arrest and sudden death.
      METHODS: The study is based on a hermeneutic lifeworld approach. Qualitative
      interviews were conducted with 10 EMS personnel from an EMS agency in southern
      Sweden. RESULTS: The EMS personnel interviewed felt responsible for both patient
      care and family care, and sometimes failed to prioritize these responsibilities
      as a result of their own perceptions, feelings and reactions. Moving from patient
      care to family care implied a movement from well-structured guidance to a
      situational response, where the personnel were forced to balance between
      interpretive reasoning and a more direct emotional response, at their own
      discretion. With such affective responses in decision-making, the personnel
      risked erroneous conclusions and care relationships with elements of dishonesty,
      misguided benevolence and false hopes. The ability to recognize and respond to
      people's existential questions and needs was essential. It was dependent on the
      EMS personnel's balance between closeness and distance, and on their courage in
      facing the emotional expressions of the families, as well as the personnel's own
      vulnerability. The presence of family members placed great demands on mobility
      (moving from patient care to family care) in the decision-making process,
      invoking a need for ethical competence. CONCLUSION: Ethical caring competence is
      needed in the care of bereaved family members to avoid additional suffering.
      Opportunities to reflect on these situations within a framework of care ethics,
      continuous moral education, and clinical ethics training are needed. Support in
      dealing with personal discomfort and clear guidelines on family support could
      benefit EMS personnel.

PMID- 22591931
TI  - Post-traumatic stress disorder and job stress among firefighters of urban Japan.
AB  - INTRODUCTION: Post-traumatic stress disorder (PTSD) is a common condition among
      Japanese firefighters. The purpose of this study was to clarify the relationship
      of PTSD scores to job stress, social support, and depressive stress among
      Japanese firefighters. METHODS: A total of 1,667 Japanese firefighters working
      for the local government completed a questionnaire that was used to gather
      information pertaining to age, gender, job type, job class, marital status, and
      smoking and drinking habits. Questionnaires from the Center for Epidemiologic
      Studies Depression Scale (CES-D), the Japanese version of the U.S. National
      Institute for Occupational Safety and Health (NIOSH) Generic Job Stress
      Questionnaire, and the IES-R were also used. RESULTS: After adjustment for age
      and gender, subjects in the PTSD-positive group had significantly higher scores
      for inter-group conflict, role ambiguity, and CES-D, as well as significantly
      lower scores for social support from their supervisors compared to those in the
      PTSD-negative group. CONCLUSIONS: High inter-group conflict and role ambiguity,
      as well as low social support from supervisors and the presence of depressive
      symptoms, may influence the development of PTSD among Japanese firefighters.

PMID- 22591932
TI  - The ethics of resuscitation: how do paramedics experience ethical dilemmas when
      faced with cancer patients with cardiac arrest?
AB  - INTRODUCTION: Research on prehospital emergency work traditionally has focused on
      medical issues, but paramedics often have to make ethical choices. The goal of
      this exploratory study was to understand how paramedics experience difficult
      ethical dilemmas regarding resuscitation of cancer patients. METHODS: Paramedics
      from ambulance services in Norway were interviewed about resuscitation of cancer
      patients with cardiac arrest. The qualitative study included naturalistic, semi
      structured interviews and a cognitive-emotional, interpretive approach. RESULTS:
      All study participants believed that it ethically can be correct not to
      resuscitate if the patient is expected to survive for only a short time with a
      very low quality of life and severe negative illness experiences. However, this
      belief sometimes failed to match formal or informal guidelines and contextual
      factors such as expectations of relatives. When confronting these challenges, the
      majority of the paramedics relied heavily on the advice of medical experts, but
      some had to make more autonomous decisions. DISCUSSION: The concept of a double
      pressure situation can be used to analyze the ethical dilemmas regarding
      resuscitation of cancer patients. The pressure from "below" is grounded in
      individual caring frameworks, and in the belief that it can be wrong to
      resuscitate. The pressure from "above" is objective and system-related, related
      to uncertainty, and grounded in the fundamental and irreducible value of human
      life. CONCLUSIONS: The findings of this qualitative, exploratory study suggest
      that ethical concepts and analyses of double pressure situations should have an
      important role in education and training designed to prepare emergency personnel
      for difficult life and death choices. More research is needed to shed light on
      how ethical dilemmas arise in prehospital work.

PMID- 22591933
TI  - Time for order in chaos! A health system framework for foreign medical teams in
      earthquakes.
AB  - The number of reported natural disasters is increasing, as is the number of
      foreign medical teams (FMTs) sent to provide relief. Studies show that FMTs are
      not coordinated, nor are they adapted to the medical needs of victims. Another
      key challenge to the response has been the lack of common terminologies,
      definitions, and frameworks for FMTs following disasters.In this report, a
      conceptual health system framework that captures two essential components of
      health care response by FMTs after earthquakes is presented. This framework was
      developed using expert panels and personal experience, as well as an exhaustive
      literature review.The framework can facilitate decisions for deployment of FMTs,
      as well as facilitate coordination in disaster-affected countries. It also can be
      an important tool for registering agencies that send FMTs to sudden onset
      disasters, and ultimately for improving disaster response.

PMID- 22591934
TI  - Incidence of tension pneumothorax in police officers feloniously killed in the
      line of duty: a ten-year retrospective analysis.
AB  - BACKGROUND: According to US military data, tension pneumothorax (TPx) is the
      second leading cause of possibly preventable combat death after isolated
      extremity hemorrhage. The purpose of this study was to determine whether TPx
      similarly represents a significant cause of possibly preventable death in police
      officers. METHODS: FBI data for the years 1998 through 2007 were reviewed. Cases
      were included if officers were on-duty at the time of fatal injury, and died
      within one hour from time of wounding from penetrating torso trauma. After case
      identification, letters were sent to the departments of victim officers
      requesting autopsy reports. RESULTS: One hundred and eight victim officers met
      inclusion criteria. Four charts were excluded due to inability to re-identify
      officers. Departmental response rate was 83.7%. Autopsy reports were provided for
      60 officers (57.7%). All officers died from gunshot wounds. No coroner
      specifically identified TPx as either a direct cause of death or a contributing
      factor (95% CI, 0.00%-5.96%). CONCLUSION: In contrast to the military experience,
      TPx appears to be a rare cause of possibly preventable death in police officers.
      Further study of non-fatal "near miss" events will be required to determine the
      actual need for law enforcement-specific medical training in the recognition and
      management of TPx.

PMID- 22591935
TI  - Vulnerability and resilience in a group intervention with hospital personnel
      during exposure to extreme and prolonged war stress.
AB  - The current study presents a pilot demonstration of a new therapeutic procedure
      to mitigate symptoms of post-traumatic stress disorder (PTSD). The pilot took
      place during the Second Lebanon War. Vulnerability and resilience statements, as
      well as post-traumatic symptoms, were measured among special army administrative
      staff (SAAS) who worked in a hospital setting during extreme and prolonged war
      stress. All 13 soldiers in the unit studied participated in seven group therapy
      intervention sessions. It was hypothesized that shifting the focus of therapeutic
      intervention from the scenes of the events to the personal and professional
      narratives of preparing for the event would change the content of the soldiers'
      narratives. It was believed that subtracting the number of positive statements
      from the number of negative statements would yield increasingly higher
      "resilience scores" during and after the war. It also was believed that such a
      change would be reflected in reduction of post-traumatic symptoms. As expected,
      the participants showed a decrease in vulnerability and an increase in resilience
      contents, as well as a decrease in traumatic symptoms during and after the war.
      These findings may reflect the effects of the ceasefire, the mutually supportive
      attitude of the participants, and the therapeutic interventions.

PMID- 22591936
TI  - Elastic properties of the abdominal aorta in the children with bicuspid aortic
      valve: an observational study.
AB  - OBJECTIVE: Abnormalities of the aortic root and ascending aorta are common in
      patients with a bicuspid aortic valve (BAV). The aim of this study was to
      evaluate the stiffness of the abdominal aorta in children with BAV. METHODS: In
      this cross-sectional observational study, we evaluated 35 children with normally
      functioning or mildly regurgitant BAV and 35 healthy children as controls. All
      children were noninvasively evaluated with transthoracic echocardiography.
      Annulus of aorta and abdominal aorta diameters were measured. Aortic strain (S),
      pressure strain elastic modulus (Ep), pressure strain normalized by diastolic
      pressure (Ep*), aortic stiffness beta index (betaSI) and, aortic distensibility
      (DIS) were calculated using the measured data. In evaluation of the data
      Student's t-test, Chi-square test, Pearson's correlation and multivariate linear
      regression analysis were used. RESULTS: Diameter of the aortic annulus was found
      significantly larger in the children with BAV than the control group (p<0.05).
      The abdominal aorta systolic and diastolic diameters were similar in the two
      groups (p>0.05). The children with BAV exhibited significantly lower S (0.210 +/-
      0.04/0.267 +/- 0.07, p<0.001) and DIS (1.04 +/- 0.2/1.4 +/- 0.4 10(-6) cm(2)
      dyne(-1), p<0.001); and higher Ep (200 +/- 39/153 +/- 47 N/m(-2), p<0.001), Ep*
      (3.42 +/- 0.9/2.5 +/- 0.9, p<0.001) and betaSI (1.1 +/- 0.3/0.84 +/- 0.3,
      p<0.001) than the control group. There was no correlation between the systolic
      and diastolic diameters of abdominal aorta and aortic elasticity parameters
      (p>0.05). CONCLUSION: Bicuspid aortic valve is associated with an increased
      abdominal aortic stiffness in children. However, impaired abdominal aortic
      elasticity is not due to abdominal aortic dilatation. These findings require
      validation by further studies.

PMID- 22591937
TI  - Pulsatile venous waveform quality in Fontan circulation-clinical implications,
      venous assists options and the future.
AB  - OBJECTIVE: Functionally univentricular heart (FUH) anomalies are the leading
      cause of death from all structural birth defects. Total cavopulmonary connection
      (TCPC) is the last stage of the palliative surgical reconstruction with
      significant late hemodynamic complications requiring high-risk heart
      transplantation. Alternative therapeutic options for these critically ill
      patients are crucial. In Phase I, we investigated the effect of pulsatility of
      venous flow (VF) waveform on the performance of functional and "failing" Fontan
      (FF) patients based on conduit power loss. In phase 2, the effect of enhanced
      external counter pulsation on Fontan circulation flow rates is monitored.
      METHODS: In phase 1, Doppler VFs were acquired from FF patients with ventricle
      dysfunction. Using computational fluid dynamics (CFD), hemodynamic efficiencies
      of the FF, functional and in-vitro generated mechanically assisted VF waveforms
      were evaluated. In phase 2, Fontan circulation on sheep model was created and
      enhanced external counter pulsation (EECP) applied. RESULTS: Variations in the
      pulsatile content of the VF waveforms altered conduit efficiency notably. High
      frequency and low amplitude oscillations lowered the pulsatile component of power
      losses in FF VF waveforms. The systemic venous flow, pulmonary artery and aorta
      flows increased by utilizing EECP. CONCLUSION: Our data highlighted the
      significance of VF pulsatility on energy efficiency inside SV circulation and the
      feasibility of VF waveform optimization. EECP assist in Fontan circulation can
      result in venous flow augmentation.

PMID- 22591938
TI  - [Normal value correlates of carotid intima- media thickness and affecting
      parameters in healthy adults].
AB  - OBJECTIVE: Early changes in atherosclerosis can be diagnosed by the carotid
      artery intima-media thickness (CIMT) measurement. Normal range of CIMT in healthy
      subjects has not been studied yet in our country. Therefore, the aim of this
      study was to measure the CIMT in healthy individuals and investigate affecting
      parameters of CIMT. METHODS: Overall, 2298 subjects, aged 18 to 92 years were
      undergone CIMT measurement in this observational cohort study. 151 healthy adult
      subjects, aged 20 to 79 year without atherosclerotic risk factors, normal body
      mass index and normal metabolic parameters were selected to establish normative
      CIMT values. Correlations between CIMT and atherosclerotic risk factors were
      evaluated in the Turkish population. The independent variables associated with
      CIMT were evaluated with multiple linear regression analysis. RESULTS: CIMT value
      was 0.458 +/- 0.116 mm in males and 0.47 +/- 0.104 mm in females. Mean values of
      CIMT (in mm) for healthy reference sample aged 20-29, 30-39, 40-49, 50-59, 60-69
      and 70-79 years were 0.402; 0.466; 0.492; 0.586; 0.692 and 0.733, respectively.
      CIMT increased significantly (p<0.001) by 0.066 mm, in every decade. Correlates
      of CIMT were age, visceral fat level, fasting serum glucose, total and low
      density lipoprotein cholesterol. Multiple linear regression analysis revealed
      that age was the single independent predictor of CIMT thickness in healthy
      individuals (beta=0.007, 95% CI: 0.006-0.008, p<0.001). CONCLUSION: CIMT was
      0.458 +/- 0.116 mm in men and 0.47 +/- 0.104 mm in Turkish healthy adults. Age
      was the only predictor of CIMT. CIMT measurement can be used in the assessment of
      early atherosclerosis burden in adults.

PMID- 22591939
TI  - Mid-term follow-up of pulmonary valve bioprostheses in adults with congenital
      heart disease.

PMID- 22591940
TI  - Percutaneous coronary intervention in a patient with situs inversus and
      dextrocardia.

PMID- 22591941
TI  - Angina and origin of three major coronary arteries from independent ostia in
      right coronary sinus.

PMID- 22591942
TI  - [Successful catheter ablation in a newborn with supraventricular tachycardia
      resistant to medical therapy].

PMID- 22591943
TI  - Transcatheter antegrade perforation and covered stent implantation to subatretic
      coarctation.

PMID- 22591944
TI  - Ogilvie syndrome: a rare but lethal intestinal complication of coronary
      revascularization.

PMID- 22591945
TI  - Interleukin-10 expression during the acute phase is a putative prerequisite for
      delayed viral elimination in a murine model for multiple sclerosis.
AB  - Reduced protective immunity leads to viral persistence and demyelination in
      Theiler's murine encephalomyelitis. The aim of the present study was to compare
      the phenotype of brain-infiltrating leukocytes and cytokine expression in
      susceptible SJL and resistant C57BL/6 mice during Theilervirus-induced acute
      polioencephalitis. In contrast to C57/BL6 mice, SJL mice show an increased number
      of Foxp3(+) regulatory T cells and CD45R(+) B cells associated with delayed viral
      elimination and elevated IL-10 mRNA transcripts in the brain. Results
      substantiate the hypothesis that an imbalanced cytokine milieu during the early
      infection phase contributes to ineffective antiviral immunity in animals with a
      susceptible genetic background.

PMID- 22591946
TI  - Alteration of immunologic responses on peripheral blood in the acute phase of
      ischemic stroke: blood genomic profiling study.
AB  - OBJECTIVE: Peripheral blood cells and inflammatory mediators have a detrimental
      effect on brain during cerebral ischemia. We investigated the immunologic changes
      on peripheral blood in the acute phase of ischemic stroke using RNA microarray.
      METHODS: mRNA microarray and real time-polymerase chain reaction (RT-PCR) for
      genes of interest in microarray data were analyzed in 12 stroke patients and 12
      controls. Plasma matrix metalloproteinase-9 (MMP-9) concentrations were measured
      in 120 stroke patients and 82 controls. RESULTS: In microarray analysis, a total
      of 11 genes of interest showed different expression in patients with ischemic
      stroke. The three most highly expressed genes were C19orf59 (chromosome 19 open
      reading frame 59), MMP9 and IL18RAP (interleukin-18 receptor accessory protein),
      whereas gene with the lowest expression was GNLY (granulysin). The expression
      patterns of three selected genes (MMP9, IL18RAP and GNLY) were validated by RT
      PCR. The plasma concentration of MMP-9 was significantly elevated in the stroke
      patients, and showed a weakly positive correlation with infarct volume. Gene set
      enrichment analysis (GSEA) showed that gene sets related to immunity and defense,
      signal transduction, transport and cell adhesion were significant in acute
      ischemic stroke. CONCLUSIONS: In the peripheral blood, numerous genes of
      inflammatory mediators, including MMP9, IL18RAP and GNLY, are altered in the
      acute phase of ischemic stroke. This stroke-specific gene expression profiling
      provides valuable information about the role of peripheral inflammation to the
      pathophysiological mechanism of ischemic stroke.

PMID- 22591947
TI  - Exploring the limits in low rectal cancer.

PMID- 22591949
TI  - Results of a transtheoretical model-based alcohol, tobacco and other drug
      intervention in middle schools.
AB  - BACKGROUND: Early use of alcohol, tobacco, and other drugs threatens the physical
      and mental well-being of students and continued use negatively affects many areas
      of development. An internet-based, tailored intervention based on the
      Transtheoretical Model of Behavior Change was delivered to middle school students
      to reduce alcohol, tobacco, and other drug use. This internet-based approach
      requires very little faculty and staff time, which is efficient given curricular
      demands. METHODS: Twenty-two middle schools in the United States were matched and
      randomly assigned to either the intervention or control conditions (N=1590
      students who had ever used substances). Participants received one pre-test
      assessment, three thirty-minute intervention sessions over three months, and two
      post-test assessments (3 and 14 months after pre-test, respectively). RESULTS:
      Random effects logistic models showed significant treatment effects for the
      intervention group when compared to the control group at the 3-month post-test.
      CONCLUSIONS: This program has the potential to be applied as stand-alone practice
      or as part of more intensive interventions to promote substance use cessation.

PMID- 22591948
TI  - Postoperative morbidity and mortality after mesorectal excision with and without
      lateral lymph node dissection for clinical stage II or stage III lower rectal
      cancer (JCOG0212): results from a multicentre, randomised controlled, non
      inferiority trial.
AB  - BACKGROUND: Mesorectal excision is the international standard surgical procedure
      for lower rectal cancer. However, lateral pelvic lymph node metastasis
      occasionally occurs in patients with clinical stage II or stage III rectal
      cancer, and therefore mesorectal excision with lateral lymph node dissection is
      the standard procedure in Japan. We did a randomised controlled trial to confirm
      that the results of mesorectal excision alone are not inferior to those of
      mesorectal excision with lateral lymph node dissection. METHODS: This study was
      undertaken at 33 major hospitals in Japan. Eligibility criteria included
      histologically proven rectal cancer of clinical stage II or stage III, with the
      main lesion located in the rectum with the lower margin below the peritoneal
      reflection, and no lateral pelvic lymph node enlargement. After surgeons had
      confirmed macroscopic R0 resection by mesorectal excision, patients were
      intraoperatively randomised to mesorectal excision alone or with lateral lymph
      node dissection. The groups were balanced by a minimisation method according to
      clinical N staging (N0 or N1, 2), sex, and institution. Allocated procedure was
      not masked to investigators or patients. This study is now in the follow-up
      stage. The primary endpoint is relapse-free survival and will be reported after
      the primary analysis planned for 2015. Here, we compare operation time, blood
      loss, postoperative morbidity (grade 3 or 4), and hospital mortality between the
      two groups. Analysis was by intention-to-treat. This trial is registered with
      ClinicalTrials.gov, number NCT00190541. FINDINGS: 351 patients were randomly
      assigned to mesoretcal excision with lateral lymph node dissection and 350 to
      mesorectal excision alone, between June 11, 2003, and Aug 6, 2010. One patient in
      the mesorectal excision alone group underwent lateral lymph node dissection, but
      was analysed in their assigned group. Operation time was significantly longer in
      the mesorectal excision with lateral lymph node dissection group (median 360 min,
      IQR 296-429) than in the mesorectal excision alone group (254 min, 210-307,
      p<0.0001). Blood loss was significantly higher in the mesorectal excision with
      lateral lymph node dissection group (576 mL, IQR 352-900) than in the mesorectal
      excision alone group (337 mL, 170-566; p<0.0001). 26 (7%) patients in the
      mesorectal excision with lateral lymph node dissection group had lateral pelvic
      lymph node metastasis. Grade 3-4 postoperative complications occurred in 76 (22%)
      patients in the mesorectal excision with lateral lymph node dissection group and
      56 (16%) patients in the mesorectal excision alone group. The most common grade 3
      or 4 postoperative complication was anastomotic leakage (18 [6%] patients in the
      mesorectal excision with lateral lymph node dissection group vs 13 [5%] in the
      mesorectal excision alone group; p=0.46). One patient in the mesorectal excision
      with lateral lymph node dissection group died of anastomotic leakage followed by
      sepsis. INTERPRETATION: Mesorectal excision with lateral lymph node dissection
      required a significantly longer operation time and resulted in significantly
      greater blood loss than mesorectal excision alone. The primary analysis will help
      to show whether or not mesorectal excision alone is non-inferior to mesorectal
      excision with lateral lymph node dissection. FUNDING: National Cancer Center,
      Ministry of Health, Labour and Welfare of Japan.

PMID- 22591950
TI  - Neurophysiological effects of modafinil on cue-exposure in cocaine dependence: a
      randomized placebo-controlled cross-over study using pharmacological fMRI.
AB  - OBJECTIVE: Enhanced reactivity to substance related cues is a central
      characteristic of addiction and has been associated with increased activity in
      motivation, attention, and memory related brain circuits and with a higher
      probability of relapse. Modafinil was promising in the first clinical trials in
      cocaine dependence, and was able to reduce craving in addictive disorders.
      However, its mechanism of action remains to be elucidated. In this functional
      magnetic resonance imaging (fMRI) study therefore, cue reactivity in cocaine
      dependent patients was compared to cue reactivity in healthy controls (HCs) under
      modafinil and placebo conditions. METHODS: An fMRI cue reactivity study, with a
      double-blind, placebo-controlled cross-over challenge with a single dose of
      modafinil (200mg) was employed in 13 treatment seeking cocaine dependent patients
      and 16 HCs. RESULTS: In the placebo condition, watching cocaine-related pictures
      (versus neutral pictures) resulted in higher brain activation in the medial
      frontal cortex, anterior cingulate cortex, angular gyrus, left orbitofrontal
      cortex, and ventral tegmental area (VTA) in the cocaine dependent group compared
      to HCs. However, in the modafinil condition, no differences in brain activation
      patterns were found between cocaine dependent patients and HCs. Group
      interactions revealed decreased activity in the VTA and increased activity in the
      right ACC and putamen in the modafinil condition relative to the placebo
      condition in cocaine dependent patients, whereas such changes were not present in
      healthy controls. Decreases in self-reported craving when watching cocaine
      related cues after modafinil administration compared to the placebo condition
      were associated with modafinil-induced increases in ACC and putamen activation.
      CONCLUSIONS: Enhanced cue reactivity in the cocaine dependent group compared to
      healthy controls was found in brain circuitries related to reward, motivation,
      and autobiographical memory processes. In cocaine dependent patients, these
      enhanced brain responses were attenuated by modafinil, mainly due to decreases in
      cue- reactivity in reward-related brain areas (VTA) and increases in cue
      reactivity in cognitive control areas (ACC). These modafinil-induced changes in
      brain activation in response to cocaine-related visual stimuli were associated
      with diminished self-reported craving. These findings imply that in cocaine
      dependent patients, modafinil, although mainly known as a cognitive enhancer,
      acts on both the motivational and the cognitive brain circuitry.

PMID- 22591951
TI  - Development and initial validation of a measure of motives for pregaming in
      college students.
AB  - OBJECTIVE: Pregaming (i.e., drinking alcohol prior to going out) is a common and
      risky drinking practice on college campuses. Yet, little is known about what
      motivates students to pregame as no motives measure exists specifically targeting
      pregaming. The current study describes the development and initial validation of
      a measure to assess motives for pregaming and to evaluate associations between
      these motives and pregaming behavior. METHOD: In a multi-stage process using
      three different college samples, both qualitative (i.e., focus groups) and
      quantitative methods were used to derive the Pregaming Motives Measure (PGMM).
      After initial item generation (Stage I: N=43, 74% male) and refinement with
      exploratory factor analysis (Stage II: N=206, 61% male), a confirmatory factor
      analysis was performed to establish the structure of the PGMM (Stage III: N=321,
      34% male). The pattern of associations of the derived factors, pregaming
      behavior, and general drinking motives was explored to provide evidence for
      initial construct validity. Last, the indirect effect of pregaming motives on
      alcohol problems via pregaming behavior was assessed. RESULTS: Findings indicated
      that the PGMM differed both in content from general drinking motives and that the
      PGMM items generated load on factors labeled Inebriation/Fun, Instrumental, and
      Social Ease. Moreover, the Inebriation/Fun and Instrumental motives were
      significantly associated with pregaming behavior. PGMM motives also both directly
      and indirectly predicted alcohol-related consequences. CONCLUSIONS: Findings
      corroborate other data on pregaming, suggesting that this behavior may be driven
      by desires for quick inebriation and conviviality and related to problems only
      via increased drinking. The PGMM offers targeted assessment of pregaming and
      other social drinking behavior that can lead to deleterious outcomes.

PMID- 22591952
TI  - Effects of cortisol secreted via a 12-h infusion of adrenocorticotropic hormone
      on mineral homeostasis and bone metabolism in ovariectomized cows.
AB  - To evaluate the effects of endogenously secreted cortisol on mineral homeostasis
      and bone metabolism in cows, 4 ovariectomized Holstein cows were infused for 12 h
      with either an adrenocorticotropic hormone (ACTH) solution (0.5 mg/2 L isotonic
      NaCl solution per cow) or isotonic NaCl solution in a 2*2 crossover design. ACTH
      infusion stimulated cortisol secretion and increased plasma cortisol
      concentrations for 18 h (P<0.001), leading to an elevated plasma glucose
      concentration until 36 h (P<0.001). Plasma calcium and magnesium concentrations
      in ACTH-infused cows fluctuated within normal ranges, whereas hypophosphatemia
      was observed unequivocally. The biochemical bone resorption markers tartrate
      resistant acid phosphatase 5b and hydroxyproline decreased following ACTH
      infusion (P<0.001 and P=0.003, respectively). Similarly, the bone formation
      marker, bone-specific alkaline phosphatase, decreased continuously until 72 h
      after the ACTH infusion (P<0.001). These results demonstrate that increased
      secretion of cortisol via a 12-h ACTH infusion disrupted homeostasis of inorganic
      phosphate and suppressed bone metabolism in ovariectomized cows without involving
      gonadal steroid hormones.

PMID- 22591953
TI  - A proteomic analysis of serum from dogs before and after a controlled weight-loss
      program.
AB  - The objective of this study was to investigate how weight-loss program would
      alter the proteome of the serum of Beagle dogs. For this purpose, serum samples
      from 5 Beagle dogs, before and after weight loss, were analyzed using 2
      dimensional electrophoresis. Protein profiles of all samples were obtained,
      divided into 2 classes (obese and lean), and compared using specific 2
      dimensional software, giving a total of 144 spot matches. Statistical analysis
      revealed 3 spot matches whose expressions were modulated in response to weight
      loss: 2 protein spots were upregulated and 1 protein spot was downregulated in
      the obese state in comparison with the lean state of the dogs. Mass spectrometric
      identification of differentially regulated spots revealed that these protein
      spots corresponded to retinol-binding protein 4, clusterin precursor, and alpha-1
      antitrypsin, respectively, which could be considered potential markers of obesity
      and obesity-related disease processes in dogs.

PMID- 22591954
TI  - Adult obesity: panel study from native Amazonians.
AB  - This paper examines three morphological indicators measuring obesity among a
      native Amazonian population of foragers-farmers in Bolivia (Tsimane') and
      estimates the associations between them and standard covariates of obesity (e.g.,
      socioeconomic status [SES]). We collected annual data from 350 non-pregnant women
      and 385 men >=20 years of age from all 311 households in 13 villages during five
      consecutive years (2002-2006). We used three indicators to measure obesity: body
      mass index (BMI), waist circumference (WC), and body fat using bioelectrical
      impedance analysis (BF-BIA). We ran separate individual random-effect panel
      multiple regressions for women and men with wealth, acculturation, health, and
      household food availability as key covariates, and controlled for village and
      year fixed effects and village*year interaction effects. Although BMI increases
      by a statistically significant annual growth rate of 0.64% among women and 0.37%
      among men over the five years, the increase does not yield significant biological
      meanings. Neither do we find consistent and biologically meaningful covariates
      associated with adult obesity.

PMID- 22591955
TI  - Movement-related potentials point towards an impaired tuning of reafferent
      sensory feedback by preceding motor activation in schizophrenia.
AB  - The link between focal motor system activation and reafferent sensory feedback is
      thought to be crucial for the perception that a movement is actively performed.
      In this article, we examine how schizophrenia affects the relationship between
      motor and somatosensory system activation. Movement-related potential source
      analysis allowed us to separate and compare motor activation deficits and
      reafferent feedback processing. We analyzed lateralized movement-related
      potentials during choice reaction movements in 16 subjects with
      schizophrenia/schizoaffective disorder. These subjects had partial remissions
      with predominantly negative symptoms and were compared to an age-matched healthy
      control group. In the schizophrenia/schizoaffective group, dipole source analysis
      indicated a significantly reduced lateralized sensorimotor activation immediately
      preceding movement execution. In contrast, activation by reafferent feedback was
      relatively unimpaired. Subjects with schizophrenia/schizoaffective disorder
      lacked a focal motor and reafferent sensory processing correlation, which can be
      identified through a significantly different regression slope from healthy
      controls. Reduced action-related motor system activation in subjects with
      schizophrenia/schizoaffective disorder was associated with preserved activation
      by reafferent sensory feedback. Most importantly, motor-sensory tuning, i.e. a
      specific enhancement of sensory information necessary to monitor movements, could
      not be found in subjects with schizophrenia/schizoaffective disorder. Our data
      provide further evidence for disturbed motor-sensory interactions in
      schizophrenia.

PMID- 22591956
TI  - Fluorometric study of fluoxetine DNA binding.
AB  - Fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI), is commonly
      prescribed to treat depression. The interaction between FLX antidepressant and
      calf thymus DNA (ctDNA) was investigated under simulated physiological conditions
      (Tris-HCl buffer at pH 7.4) using methylene blue [3,7-bis(dimethylamino) pheno
      thrazin-5-ium chloride] (MB) dye as a probe using fluorescence spectroscopy. A
      strong fluorescence quenching reaction of DNA to FLX was observed. The
      corresponding numbers of binding sites (n) and binding constants (K(f)) of DNA
      with FLX at 281, 310 and 318K were calculated 2.1*10(5), 6.7*10(5) and 9.7*10(5)
      respectively. It can be concluded that FLX molecules could interact with ctDNA
      via outside, non-intercalative, binding as evidenced by quenching study with I(
      ), ionic strength with NaCl and competitive investigation with MB. Thermodynamic
      parameters, enthalpy (DeltaH) and entropy (DeltaS) changes were calculated
      according to Van't Hoff equation, which indicated that reaction is entropically
      driven. Furthermore, the interaction of FLX with poly A-T and poly C-G were
      carried out in order to comprehend the binding location of drug to DNA.

PMID- 22591957
TI  - Comparative effectiveness for survival and renal function of partial and radical
      nephrectomy for localized renal tumors: a systematic review and meta-analysis.
AB  - PURPOSE: The relative effectiveness of partial vs radical nephrectomy remains
      unclear in light of the recent phase 3 European Organization for the Research and
      Treatment of Cancer trial. We performed a systematic review and meta-analysis of
      partial vs radical nephrectomy for localized renal tumors, considering all cause
      and cancer specific mortality, and severe chronic kidney disease. MATERIALS AND
      METHODS: Cochrane Central Register of Controlled Trials, MEDLINE(r), EMBASE(r),
      Scopus and Web of Science(r) were searched for sporadic renal tumors that were
      surgically treated with partial or radical nephrectomy. Generic inverse variance
      with fixed effects models were used to determine the pooled HR for each outcome.
      RESULTS: Data from 21, 21 and 9 studies were pooled for all cause and cancer
      specific mortality, and severe chronic kidney disease, respectively. Overall
      31,729 (77%) and 9,281 patients (23%) underwent radical and partial nephrectomy,
      respectively. According to pooled estimates partial nephrectomy correlated with a
      19% risk reduction in all cause mortality (HR 0.81, p < 0.0001), a 29% risk
      reduction in cancer specific mortality (HR 0.71, p = 0.0002) and a 61% risk
      reduction in severe chronic kidney disease (HR 0.39, p < 0.0001). However, the
      pooled estimate of cancer specific mortality for partial nephrectomy was limited
      by the lack of robustness in consistent findings on sensitivity and subgroup
      analyses. CONCLUSIONS: Our findings suggest that partial nephrectomy confers a
      survival advantage and a lower risk of severe chronic kidney disease after
      surgery for localized renal tumors. However, the results should be evaluated in
      the context of the low quality of the existing evidence and the significant
      heterogeneity across studies. Future research should use higher quality evidence
      to clearly demonstrate that partial nephrectomy confers superior survival and
      renal function.

PMID- 22591958
TI  - Revisions of mid urethral slings can be accomplished in the office.
AB  - PURPOSE: Mid urethral slings occasionally require revision for obstructive
      voiding symptoms or vaginal extrusion. Our approach has been to offer revision in
      office or resection done under local anesthesia when the patient is agreeable and
      deemed an appropriate candidate. The results and complications of these
      procedures are presented. MATERIALS AND METHODS: We retrospectively reviewed the
      charts of patients from January 2003 to October 2010 to determine the subset with
      mid urethral sling insertion who subsequently underwent revision in the office or
      operating room, as identified through the Northwestern Medical Enterprise Data
      Warehouse. The CPT code for female sling insertion (57288) or revision/removal
      (57287) was used. RESULTS: A total of 41 revisions were performed in 28 of the
      118 patients (23.7%) who underwent synthetic sling insertion. Reasons for
      adjustment were an intravesical sling (1 operating room case), extruded vaginal
      mesh (7 operating room and 19 office) and obstructive voiding symptoms (7
      operating room and 7 office). Obstructive voiding symptoms in 6 of 7 operating
      room and 6 of 7 office patients improved immediately after sling release. There
      were no complications in either group but 3 office patients required repeat
      revision in the operating room due to inability to tolerate the procedure in 2
      and to nonrelief of symptoms in 1. A total of 13 operating room adjustments were
      made according to surgeon preference while 2 patients elected the operating room,
      although adjustment in office was offered. CONCLUSIONS: Sling adjustment due to
      vaginal mesh extrusion or obstructive voiding symptoms can be successfully
      performed in the office with good result. When greater adjustment is needed, the
      operating room may be preferable. Surgeons should make these decisions based on
      their comfort level and patient preference.

PMID- 22591959
TI  - A prospective randomized controlled trial of the transobturator tape and tissue
      fixation mini-sling in patients with stress urinary incontinence: 5-year results.
AB  - PURPOSE: We present the 5-year results of a randomized controlled trial comparing
      the efficacy of a transobturator tape operation with an adjustable mini-sling
      (tissue fixation system) for the treatment of stress urinary incontinence.
      MATERIALS AND METHODS: This prospective randomized controlled trial comprised 80
      female patients with only urodynamically proven stress urinary incontinence. The
      participants were randomly allocated to the transobturator tape group or the
      tissue fixation system group according to a computer program at a maternity
      research hospital. The patients were reassessed 5 years after surgery. Primary
      outcome measures were objective and subjective cure rates as well as total
      failure rate. RESULTS: Total followup was 64 months (range 58 to 70). The
      objective cure, subjective cure and failure rates in the tissue fixation system
      group were 83% (30 cases), 6% (2) and 11% (4), respectively. The objective cure,
      subjective cure and failure rates in the transobturator tape group were 75% (27
      cases), 3% (1) and 22% (8), respectively. The difference in objective cure rates
      was statistically significant in favor of the tissue fixation system (p = 0.029).
      The difference in decreased cure rates between 5 and 3 years was 7% (90% to 83%)
      for the tissue fixation system vs 9% (84% to 75%) for the transobturator tape.
      The relative decrease in cure rates between the 2 groups was not statistically
      significant (p = 0.16). CONCLUSIONS: Contrary to reports in the literature of
      poor results with mini-slings, the tissue fixation system mini-sling demonstrated
      a higher cure rate and lower complication rate than the transobturator tape.

PMID- 22591960
TI  - Nonoperative management of penetrating kidney injuries: a prospective audit.
AB  - PURPOSE: The role of nonoperative management for penetrating kidney injuries is
      unknown. Therefore, we review the management and outcome of penetrating kidney
      injuries at a center with a high incidence of penetrating trauma. MATERIALS AND
      METHODS: Data from all patients presenting with hematuria and/or kidney injury
      discovered on imaging or at surgery admitted to the trauma center at Groote
      Schuur Hospital in Cape Town, South Africa during a 19-month period (January 2007
      to July 2008) were prospectively collected and reviewed. These data were analyzed
      for demographics, injury mechanism, perioperative management, nephrectomy rate
      and nonoperative success. Patients presenting with hematuria and with an acute
      abdomen underwent a single shot excretory urogram. Those presenting with
      hematuria without an indication for laparotomy underwent computerized tomography
      with contrast material. RESULTS: A total of 92 patients presented with hematuria
      following penetrating abdominal trauma. There were 75 (80.4%) proven renal
      injuries. Of the patients 84 were men and the median age was 26 years (range 14
      to 51). There were 50 stab wounds and 42 gunshot renal injuries. Imaging
      modalities included computerized tomography in 60 cases and single shot excretory
      urography in 18. There were 9 patients brought directly to the operating room
      without further imaging. A total of 47 patients with 49 proven renal injuries
      were treated nonoperatively. In this group 4 patients presented with delayed
      hematuria, of whom 1 had a normal angiogram and 3 underwent successful
      angioembolization of arteriovenous fistula (2) and false aneurysm (1). All
      nonoperatively managed renal injuries were successfully treated without surgery.
      There were 18 nephrectomies performed for uncontrollable bleeding (11), hilar
      injuries (2) and shattered kidney (3). Post-nephrectomy complications included 1
      infected renal bed hematoma requiring percutaneous drainage. Of the injuries
      found at laparotomy 12 were not explored, 2 were drained and 5 were treated with
      renorrhaphy. CONCLUSIONS: Penetrating trauma is associated with a high
      nephrectomy rate (24.3%). However, a high nonoperative success rate (100%) is
      achievable with minimal morbidity (9%).

PMID- 22591961
TI  - Obstetric complications of ureteroscopy during pregnancy.
AB  - PURPOSE: During pregnancy a ureteral stone and its management may pose risks for
      the mother and fetus. Definitive ureteroscopic management of an obstructing stone
      during pregnancy has been increasingly used without a reported increased
      incidence of urological complications. However, the rate of obstetric
      complications of ureteroscopy during pregnancy remains undefined. MATERIALS AND
      METHODS: Charts of pregnant women who had undergone ureteroscopy at 5 tertiary
      centers were reviewed. Patient and procedure characteristics were collected.
      Records were evaluated for the occurrence of obstetric complications in the
      postoperative period. RESULTS: A total of 46 procedures were performed in 45
      patients at 5 institutions. There were 2 obstetric complications (4.3%),
      including 1 preterm labor managed conservatively and 1 preterm labor resulting in
      preterm delivery. There was no fetal loss. No statistically significant
      characteristics were identified differentiating those patients having obstetric
      complications. CONCLUSIONS: Ureteroscopy performed during pregnancy has been
      previously reported to be urologically safe and effective for addressing ureteral
      stones. In our multi-institutional series a 4% rate of obstetric complications
      was observed. Based on this risk a multidisciplinary approach is prudent for the
      pregnant patient undergoing ureteroscopy.

PMID- 22591962
TI  - Treatment of ureteral and renal stones: a systematic review and meta-analysis of
      randomized, controlled trials.
AB  - PURPOSE: We compared the clinical outcomes of patients with ureteral or renal
      stones treated with ureteroscopy, shock wave lithotripsy using HM3 (Dornier(r))
      and nonHM3 lithotripters, and percutaneous nephrolithotomy. MATERIALS AND
      METHODS: A systematic literature search identified 6, 4 and 3 randomized,
      controlled trials of treatment of distal and proximal ureteral stones, and renal
      stones, respectively, published between 1995 and 2010. Overall stone-free, re
      treatment and complication rates were calculated by meta-analytical techniques.
      RESULTS: Based on the randomized, controlled trials evaluated the treatment of
      distal ureteral stones with semirigid ureteroscopy showed a 55% greater
      probability (pooled RR 1.55, 95% CI 1.13-2.56) of stone-free status at the
      initial assessment than treatment with shock wave lithotripsy. Patients treated
      with semirigid ureteroscopy were also less likely to require re-treatment than
      those treated with shock wave lithotripsy (nonHM3) (RR 0.14, 95% CI 0.08-0.23).
      The risk of complications was no different between the 2 modalities. Only 2 of
      the 4 randomized, controlled trials identified for proximal ureteral stones
      evaluated flexible ureteroscopy and each focused specifically on the treatment of
      stones 1.5 cm or greater, limiting their clinical relevance. The degree of
      heterogeneity among the studies evaluating renal stones was so great that it
      precluded any meaningful comparison. CONCLUSIONS: Semirigid ureteroscopy is more
      efficacious than shock wave lithotripsy for distal ureteral stones. To our
      knowledge there are no relevant randomized, controlled trials of flexible
      ureteroscopy treatment of proximal ureteral calculi of a size commonly noted in
      the clinical setting. Collectively the comparative effectiveness of ureteroscopy
      and shock wave lithotripsy for proximal ureteral and renal calculi is poorly
      characterized with no meaningful published studies.

PMID- 22591963
TI  - The international prostate symptom score overestimates nocturia assessed by
      frequency-volume charts.
AB  - PURPOSE: We analyzed differences in nocturia, as estimated by the International
      Prostate Symptom Score and 7-day frequency-volume charts. MATERIALS AND METHODS:
      A total of 398 forms were collected from 500 consecutive urological outpatients
      willing to record a 7-day frequency-volume chart. All patients completed a
      general questionnaire, an International Prostate Symptom Score, and a bladder
      symptom and bother score. Missed recordings were indicated by a coded letter.
      Patients who lacked essential data, bedtimes or an International Prostate Symptom
      Score, or who recorded the frequency-volume chart for less than 5 days were
      excluded from study. RESULTS: A total of 186 men and 115 women with a mean age of
      56 years were evaluable. In 10.6% of patients no nocturia occurred. Of those with
      nocturia 70% and 34% experienced nocturia a mean of 1 or more and 2 or more
      times, respectively. In 43% of patients the International Prostate Symptom Score
      equaled calculated categorized nocturia while 50% had a higher International
      Prostate Symptom Score nocturia score than calculated nocturia. On univariate
      analysis the correlation of International Prostate Symptom Score question 7 with
      mean nocturia increased with frequency-volume chart duration (day 1 r = 0.52 to
      day 3 r = 0.63). On longer duration frequency-volume charts the correlation
      showed no further increase. Multivariate regression analysis revealed that the
      nocturia score was determined by mean nocturia in the frequency-volume chart, the
      nocturia bother score and patient age. CONCLUSIONS: The International Prostate
      Symptom Score nocturia score overestimated nocturia in most patients, as derived
      from a 7-day frequency-volume chart. When scoring International Prostate Symptom
      Score nocturia question 7, patients included a degree of bother. The correlation
      of question 7 with mean nocturia increased with frequency-volume chart duration
      until day 3.

PMID- 22591964
TI  - TachoSil((r)) sealed tubeless percutaneous nephrolithotomy to reduce urine
      leakage and bleeding: outcome of a randomized controlled study.
AB  - PURPOSE: We determined the efficacy and safety of TachoSil((r)) in sealing the
      tract after percutaneous nephrolithotomy compared to nephrostomy tube placement.
      MATERIALS AND METHODS: A total of 100 consecutive patients scheduled for
      percutaneous nephrolithotomy were randomized 1:1 to receive a 16Fr nephrostomy
      tube (group 1) or TachoSil in the tract (group 2). All patients received a mono-J
      ureteral catheter. The primary study end points were bleeding and urinary leakage
      rates. The secondary end points were pain as assessed by the 0 to 10-point visual
      analog scale, analgesic requirement and hospital stay. RESULTS: The groups were
      comparable for preoperative and operative variables. In group 1, 3 patients were
      excluded intraoperatively because of relevant bleeding, and in group 2, 1 patient
      was excluded intraoperatively because of hydrothorax. Tract complications were
      significantly more frequent in group 1 than in group 2 (25.5% vs 2%, p <0.001).
      However, the difference in urinary leakage reached statistical significance
      (19.1% vs 2%, p = 0.007), whereas that in perirenal hematoma formation did not
      (6.4% vs 0%, p = 0.113). There was no difference between the groups in mean +/-
      SD number of analgesic doses (1.17 +/- 1.56 vs 1.20 +/- 1.69, p = 0.791) and
      visual analogue scale scores (4.77 +/- 2.28 vs 4.24 +/- 2.32, p = 0.270).
      Postoperative hospital stay was significantly shorter in group 2 than in group 1
      (5.15 +/- 1.74 vs 2.75 +/- 1.78 days, p <0.0001). CONCLUSIONS: Although failing
      to reduce pain and analgesic requirement, TachoSil provided better tract control
      and a shorter hospital stay than nephrostomy tube placement, thus allowing the
      extension of indications for tubeless percutaneous nephrolithotomy to most
      procedures.

PMID- 22591966
TI  - Voiding function in women with orthotopic neobladder urinary diversion.
AB  - PURPOSE: Most long-term morbidity after radical cystectomy is related to the
      urinary diversion or reconstruction. While there are benefits to an orthotopic
      neobladder, there can be a substantial risk of voiding dysfunction in women. We
      examine the prevalence of postoperative voiding complications in women who
      underwent orthotopic neobladder diversion. MATERIALS AND METHODS: We identified
      all women who underwent radical cystectomy and orthotopic neobladder for bladder
      cancer at our institution from 1996 to 2011 (51) and included patients with
      regular clinic followup (49). The presence and severity of incontinence and
      hypercontinence were evaluated at routine clinic visits. Unadjusted analyses were
      performed to measure the association between patient variables and voiding
      symptoms, with p < 0.05 considered significant. RESULTS: Daytime incontinence,
      nighttime incontinence and hypercontinence were reported by 43%, 55% and 31% of
      women, respectively. A neobladder-vaginal fistula developed in 3 women (6%). On
      unadjusted analysis having daytime incontinence was associated with a concurrent
      or previous hysterectomy (p = 0.031), but not with age, disease stage,
      preoperative incontinence, year of surgery or sparing the vaginal wall. The
      severity of daytime incontinence was associated with preoperative incontinence
      only (p = 0.02). The presence and severity of nighttime incontinence were
      associated with patient age only (p = 0.013, p = 0.005, respectively).
      Hypercontinence was not associated with any variable. CONCLUSIONS: Among women
      with orthotopic neobladder after radical cystectomy we identified a significant
      prevalence of voiding dysfunction. We recommend preoperative discussion of these
      possible complications with any woman interested in orthotopic neobladder to
      establish realistic expectations. For properly selected women who understand
      these risks, orthotopic neobladder may be an appropriate diversion choice.

PMID- 22591965
TI  - Outcomes of endoscopic realignment of pelvic fracture associated urethral
      injuries at a level 1 trauma center.
AB  - PURPOSE: We examined the success of early endoscopic realignment of pelvic
      fracture associated urethral injury after blunt pelvic trauma. MATERIALS AND
      METHODS: A retrospective review was performed of patients with pelvic fracture
      associated urethral injury who underwent early endoscopic realignment using a
      retrograde or retrograde/antegrade approach from 2004 to 2010 at a Level 1 trauma
      center. Followup consisted of uroflowmetry, post-void residual and cystoscopic
      evaluation. Failure of early endoscopic realignment was defined as patients
      requiring urethral dilation, direct vision internal urethrotomy, posterior
      urethroplasty or self-catheterization after initial urethral catheter removal.
      RESULTS: A total of 19 consecutive patients (mean age 38 years) with blunt pelvic
      fracture associated urethral injury underwent early endoscopic realignment.
      Twelve cases of complete urethral disruption, 4 of incomplete disruption and 3 of
      indeterminate status were noted. Mean time to realignment was 2 days and mean
      duration of urethral catheterization after realignment was 53 days. One patient
      was lost to followup after early endoscopic realignment. Using an intent to treat
      analysis early endoscopic realignment failed in 15 of 19 patients (78.9%). Mean
      time to early endoscopic realignment failure after catheter removal was 79 days.
      The cases of early endoscopic realignment failure were managed with posterior
      urethroplasty (8), direct vision internal urethrotomy (3) and direct vision
      internal urethrotomy followed by posterior urethroplasty (3). Mean followup for
      the 4 patients considered to have undergone successful early endoscopic
      realignment was 2.1 years. CONCLUSIONS: Early endoscopic realignment after blunt
      pelvic fracture associated urethral injury results in high rates of symptomatic
      urethral stricture requiring further operative treatment. Close followup after
      initial catheter removal is warranted, as the mean time to failure after early
      endoscopic realignment was 79 days in our cohort.

PMID- 22591967
TI  - Associations of commonly used medications with urinary incontinence in a
      community based sample.
AB  - PURPOSE: We examined the association between the use of medications and the
      prevalence of urinary incontinence in gender specific analyses of a community
      based, representative sample. MATERIALS AND METHODS: A population based
      epidemiological study was conducted of 5,503 men and women 30 to 79 years old
      residing in Boston, Massachusetts (baseline data collected from 2002 to 2005).
      Urological symptoms were ascertained in a 2-hour, in person interview. Urinary
      incontinence was defined as urine leakage occurring weekly or more often during
      the last year. Medications used in the last month were considered current use.
      Associations of 20+ medications and prevalent urinary incontinence were examined
      using multivariate logistic regression (ORs and 95% CIs) with adjustments for
      known urinary incontinence risk factors. RESULTS: The prevalence of urinary
      incontinence in the analysis sample was 9.0% in women and 4.6% in men. For women
      the prevalence was highest among users of certain antihistamines (28.4%) and
      angiotensin II receptor blockers (22.9%). For men the prevalence was highest
      among angiotensin II receptor blocker (22.2%) and loop diuretic (19.1%) users.
      After final multivariate adjustment there were significant positive associations
      for certain antihistamines, beta receptor agonists, angiotensin II receptor
      blockers and estrogens with urinary incontinence in women (all ORs greater than
      1.7), and a borderline significant association for anticonvulsants (OR 1.75; 95%
      CI 1.00, 3.07). Among men only anticonvulsants were associated with urinary
      incontinence after final adjustments (OR 2.50; 95% CI 1.24, 5.03), although
      angiotensin II receptor blockers showed an adjusted association of borderline
      significance (OR 2.21; 95% CI 0.96, 5.10). CONCLUSIONS: Although a cross
      sectional analysis cannot determine causality, our analysis suggests certain
      medications should be further examined in longitudinal analyses of risk to
      determine their influence on urological symptoms.

PMID- 22591968
TI  - Holmium laser enucleation versus photoselective vaporization for prostatic
      adenoma greater than 60 ml: preliminary results of a prospective, randomized
      clinical trial.
AB  - PURPOSE: To our knowledge we report the first single center, prospective,
      randomized study comparing holmium laser enucleation and high performance
      GreenLightTM prostate photoselective vaporization as surgical treatment of
      prostatic adenomas greater than 60 ml. MATERIALS AND METHODS: A total of 80
      patients with a large prostatic adenoma were randomly assigned to surgical
      treatment with holmium laser enucleation or photoselective vaporization.
      International Prostate Symptom Score, International Index of Erectile Function
      15, maximum flow rate, post-void residual urine, serum prostate specific antigen
      and transrectal ultrasound volume were recorded. RESULTS: Patient baseline
      characteristics were similar for holmium laser enucleation and photoselective
      vaporization. Operative time and catheter removal time were almost equal in the 2
      groups (p = 0.7 and 0.2, respectively). Eight vaporization cases were converted
      to transurethral prostate resection or holmium laser enucleation intraoperatively
      due to bleeding. A significantly higher maximum flow rate and lower post-void
      residual urine were noted in holmium laser cases during the entire followup (at 1
      year each p = 0.02). However, no significant difference in International Prostate
      Symptom Score, quality of life or International Index of Erectile Function-15 was
      detected. Prostate volume and serum PSA decreased 78% and 88% in the holmium
      laser group, and 52% and 60% in the vaporization group, respectively.
      CONCLUSIONS: Holmium laser enucleation and photoselective vaporization are
      effective for lower urinary tract symptoms due to a large prostatic adenoma.
      Early subjective functional results (maximum flow rate and post-void residual
      urine) of holmium laser enucleation appear to be superior to those of
      photoselective vaporization. In our hands cases intended to be treated with
      photoselective vaporization were at 22% risk of conversion to another modality.
      This could reflect our determination to vaporize to the capsule in all
      vaporization cases.

PMID- 22591969
TI  - Renal trauma from recreational accidents manifests different injury patterns than
      urban renal trauma.
AB  - PURPOSE: The majority of blunt renal trauma is a consequence of motor vehicle
      collisions and falls. Prior publications based on urban series have shown that
      significant renal injuries are almost always accompanied by gross hematuria alone
      or microscopic hematuria with concomitant hypotension. We present a series of
      blunt renal trauma sustained during recreational pursuits, and describe the
      mechanisms, injury patterns and management. MATERIALS AND METHODS: Database
      review from 1996 to 2009 identified 145 renal injuries. Children younger than age
      16 years, and trauma involving licensable motor vehicles, penetrating injuries
      and work related injuries were excluded from analysis. Grade, hematuria,
      hypotension, age, gender, laterality, mechanism, management, injury severity
      score and associated injuries were recorded. RESULTS: We identified 106 patients
      meeting the criteria and 85% of the injuries were snow sport related. Age range
      was 16 to 76 years and 92.5% of patients were male. There were 39 grade 1
      injuries, 30 grade 2, 22 grade 3, 12 grade 4 and 3 grade 5 injuries. Gross
      hematuria was present in 56.7%, 77.2% and 83.3% of grade 2, grade 3 and grade 4
      injuries, respectively. None of the patients with grade 2 or greater injuries and
      microscopic hematuria had hypotension except 1 grade 5 pedicle injury. The
      nephrectomy and renorrhaphy rate for grade 1 to grade 4 injuries was 0%.
      CONCLUSIONS: Compared to urban series of blunt renal trauma, recreationally
      acquired injuries appear to follow different patterns, including a paucity of
      associated injuries or hypotension. If imaging were limited to the presence of
      gross hematuria, or microscopic hematuria with hypotension, 23% of grade 2 to
      grade 4 injuries would be missed. Men are at higher risk than women. However,
      operative intervention is rarely helpful.

PMID- 22591970
TI  - Surgical practice patterns for male urinary incontinence: analysis of case logs
      from certifying American urologists.
AB  - PURPOSE: Several options exist for the surgical correction of male stress urinary
      incontinence including periurethral bulking agents, artificial urinary sphincters
      and the recently introduced male urethral slings. We investigated contemporary
      trends in the use of these treatments. MATERIALS AND METHODS: Annualized case log
      data for incontinence surgeries from certifying and recertifying urologists were
      obtained from the ABU (American Board of Urology), ranging from 2004 to 2010. Chi
      square tests and logistic regression models were used to evaluate the association
      between surgeon characteristics (type of certification, annual volume, practice
      type and practice location) and the use of incontinence procedures. RESULTS:
      Among the 2,036 nonpediatric case logs examined the number of incontinence
      treatments reported for certification has steadily increased over time from 1,936
      to 3,366 treatments per year from 2004 to 2010 (p = 0.008). Nearly a fifth of
      urologists reported placing at least 1 sling. The proportion of endoscopic
      procedures decreased from 80% of all incontinence procedures in 2004 to 60% in
      2010, but they remained the exclusive incontinence procedure performed by 49% of
      urologists. A urologist's increased use of endoscopic treatments was associated
      with a decreased likelihood of performing a sling procedure (OR 0.5, p <0.0005).
      Artificial urinary sphincter use remained stable, accounting for 12% of
      procedures. CONCLUSIONS: Incontinence procedures are on the rise. Urethral slings
      have been widely adopted and account for the largest increase among treatment
      modalities. Endoscopic treatments continue to be commonly performed and may
      represent overuse in the face of improved techniques. Further research is
      required to validate these trends.

PMID- 22591972
TI  - Hemophagocytic lymphohistiocytosis in a patient with angioimmunoblastic lymphoma:
      a case report and review of the literature.
AB  - Hemophagocytic lymphohistiocytosis is a rare disorder characterized by a
      proliferation of phagocytic histiocytes in hematopoietic organs. It is
      accompanied by systemic manifestations and frequently has an abrupt onset with a
      fulminant clinical course and high mortality. Awareness of this condition is
      important since early diagnosis and initiation of treatment is critical for a
      successful outcome. The authors report a patient with hemophagocytic
      lymphohistiocytosis associated with angioimmunoblastic lymphoma, describe the
      clinical and histological features of hemophagocytic lymphohistiocytosis, and
      review the literature on this condition.

PMID- 22591971
TI  - The CROES percutaneous nephrolithotomy global study: the influence of body mass
      index on outcome.
AB  - PURPOSE: In addition to more commonly forming stones, obese patients present a
      number of challenges when undergoing percutaneous nephrolithotomy. We evaluated
      percutaneous nephrolithotomy outcomes in 3,709 patients stratified by body mass
      index. MATERIALS AND METHODS: A prospective database administered by CROES
      (Clinical Research Office of the Endourological Society) captured data on 5,803
      patients treated with percutaneous nephrolithotomy between November 2007 and
      December 2009. Patients with known solitary kidney, previous percutaneous
      nephrolithotomy and congenital abnormalities were excluded from analysis. For
      statistical analysis patients were categorized as normal weight--body mass index
      18.5 to 25 kg/m(2), overweight--25 to 30, obese--30 to 40 and super obese-
      greater than 40. RESULTS: During the study period 5,803 patients underwent
      percutaneous nephrolithotomy, of whom 3,709 met the inclusion criteria. As
      expected, obesity was associated with significantly higher rates of comorbid
      conditions and anticoagulant use (p < 0.001). Operative time was significantly
      longer in obese patients and use of a balloon device for tract dilation was more
      common (each p < 0.001). The stone-free rate decreased with obesity (p = 0.009),
      corresponding to a significantly higher re-treatment rate in this group (p <
      0.001). No difference was seen in length of stay or the transfusion rate. No
      significant difference was seen in the overall complication rate among the 4
      groups (p = 0.707). CONCLUSIONS: Percutaneous nephrolithotomy may be done safely
      in obese patients, although with a longer operative time, an inferior stone-free
      rate and a higher re-intervention rate.

PMID- 22591973
TI  - Interspecies differences in membrane-associated protease activities of thyrocytes
      and their relevance for thyroid cancer studies.
AB  - BACKGROUND: To understand the role of proteases involved in human thyroid cancer
      progression and tissue invasion, thyrocytes from other species could potentially
      be used provided their characteristics are similar. It is not known whether
      dipeptidyl peptidase IV and aminopeptidase N activities, which are overexpressed
      in human thyroid cancer, are, as in human, also absent in normal thyrocytes of
      other species, making them suitable models for studies on the regulation of these
      proteases. METHODS: To assess the role of these proteases, activity was measured
      in thyroid tissue of human, mouse, rat, porcine, bovine and ovine origin. The
      lysosomal protease, dipeptidyl peptidase II, was used for comparison. RESULTS:
      Murine, rat, ovine, bovine and human thyrocytes all lacked dipeptidyl peptidase
      IV and aminopeptidase N activity, but porcine thyrocytes were found to possess
      both. In contrast, lysosomal dipeptidyl peptidase II was strongly expressed in
      all species. These activity patterns were maintained in cultured cells. Cultured
      porcine thyrocytes formed follicles with typical morphology upon stimulation with
      TSH but differed from human thyrocytes in their response to thiamazole.
      CONCLUSIONS: These species differences in the expression of dipeptidyl peptidase
      IV and aminopeptidase N, indicate that porcine thyrocytes cannot be considered
      appropriate for the study of proteases in human cancer development.

PMID- 22591975
TI  - Unhealthy behaviour is contagious: an invitation to exploit models for infectious
      diseases.
AB  - We argue that the spread of unhealthy behaviour shows marked similarities with
      infectious diseases. It is therefore interesting and challenging to use
      infectious disease methodologies for studying the spread and control of unhealthy
      behaviour. This would be a great addition to current methods, because it allows
      taking into account the dynamics of individual interactions and the social
      environment at large. In particular, the application of individual-based
      modelling holds great promise to address some major public health questions.

PMID- 22591974
TI  - The role of secondary cytoreductive surgery in patients with recurrent epithelial
      ovarian, tubal, and peritoneal cancers: a comparative effectiveness analysis.
AB  - Background. All published reports concerning secondary cytoreductive surgery for
      relapsed ovarian cancer have essentially been observational studies. However, the
      validity of observational studies is usually threatened from confounding by
      indication. We sought to address this issue by using comparative effectiveness
      methods to adjust for confounding.  Methods. Using a prospectively collected
      administrative health care database in a single institution, we identified 1,124
      patients diagnosed with recurrent epithelial, tubal, and peritoneal cancers
      between 1990 and 2009. Effectiveness of secondary cytoreductive surgery using the
      conventional Cox proportional hazard model, propensity score, and instrumental
      variable were compared. Sensitivity analyses for residual confounding were
      explored using an array approach.  Results. Secondary cytoreductive surgery
      prolonged overall survival with a hazard ratio (95% confidence interval) of 0.76
      (range 0.66-0.87), using the Cox proportional hazard model. Propensity score
      methods produced comparable results: 0.75 (range 0.64-0.86) by nearest matching,
      0.73 (0.65-0.82) by quintile stratification, 0.71 (0.65-0.77) by weighting, and
      0.72 (0.63-0.83) by covariate adjustment. The instrumental variable method also
      produced a comparable estimate: 0.75 (range 0.65-0.86). Sensitivity analyses
      revealed that the true treatment effects may approach the null hypothesis if the
      association between unmeasured confounders and disease outcome is high. 
      Conclusions. This comparative effectiveness study provides supportive evidence
      for previous reports that secondary cytoreductive surgery may increase overall
      survival for patients with recurrent epithelial, tubal, and peritoneal cancers.

PMID- 22591976
TI  - Aspirin: a history, a love story.
AB  - Most pharmacists know that aspirin's origins lie with willow bark, but they may
      be unaware of its role in the development of the pharmaceutical industry.
      Evolving from salacin (the active ingredient in many plant remedies) to salicylic
      acid (an analgesic in its own right) to the more effective, less toxic
      acetylsalicylic acid, this pain reliever cornered the nonsteroidal anti
      inflammatory market for more than 70 years. It helped the dye industry branch
      into pharmaceuticals, and is now used in multiple indications.

PMID- 22591977
TI  - Healthy aging: programs for self-management of chronic disease second of a 2-part
      series.
AB  - Part 1 of this series described several healthy aging evidence-based programs and
      discussed collaborative opportunities for senior care pharmacists within these
      programs. Offered in community-based settings such as Area Agencies on Aging and
      senior centers, these programs focus on falls prevention, physical activity,
      depression management, and substance abuse prevention. This article-Part 2
      explores chronic disease self-management programs (CDSMPs) that are designed to
      help older adults manage their chronic conditions by giving them self-confidence
      in their ability to control symptoms and manage the progression of their
      illnesses. In general, self-management programs provide older adults with
      education and tools to enable them to cope with chronic diseases such as
      diabetes, heart disease, respiratory diseases, chronic pain, and arthritis. The
      programs help participants handle stress, better manage their medications,
      discuss the benefits of and encourage physical activity and good nutrition, and
      communicate more effectively with health care providers, including pharmacists.
      Participants develop action plans related to these issues through structured
      planning and feedback exercises. As of January 2011, more than 70,000 older
      Americans have completed a CDSMP.

PMID- 22591978
TI  - Tablet splitting: a review of weight and content uniformity.
AB  - OBJECTIVE: To describe the product integrity and ethical/ legal issues associated
      with tablet splitting. DATA SOURCES: PubMed (1966-June 2011), International
      Pharmaceutical Abstract (1975-June 2011), and bibliographic searches were
      conducted. STUDY SELECTION: All studies that evaluated the weight/dose variations
      (N = 13) of split tablets were included. DATA EXTRACTION: The American
      Pharmacists Association guidelines, recommendations from the Food and Drug
      Administration, and clinical studies evaluating product integrity of split
      tablets were used to provide an overview of issues related to this practice.
      Legal considerations from various sources were also included. DATA SYNTHESIS: The
      practice of tablet splitting is increasing and is associated with variations in
      drug distributions related to the tablet-splitting technique and other causes.
      The first part of this two-part series will evaluate the product integrity and
      practice-related issues associated with tablet splitting. CONCLUSION: The
      majority of the studies associated with tablet splitting reveal large
      fluctuations in weight/dosage, but few studies evaluate variability with narrow
      therapeutic index medications. Therefore, the clinical impact of these variations
      is not globally applicable across medication classes. Although tablet splitting
      has the potential to save patients and health care organizations a significant
      amount of money, appropriateness of tablet splitting should be determined for
      individual medications and individual patients. Assessments should include an
      evaluation of patient understanding and physical abilities for tablet splitting.

PMID- 22591979
TI  - Implementation of a personal medication record program in an independent living
      facility.
AB  - OBJECTIVE: To describe the process of implementing a "Vial of Life" [Lifesaving
      Information for Emergencies] program in an independent living facility. SETTING:
      An independent living facility in the Richmond, Virginia, area. PRACTICE
      DESCRIPTION: The average age of the residents is 79.75 years, with 75% of the
      population being female. The facility offers social, cultural, and recreational
      activities, health and wellness programs, a salon, and outdoor activities.
      PRACTICE INNOVATION: Implementing the Vial of Life Project into an independent
      living facility. MAIN OUTCOME MEASUREMENTS: The number of patients who have
      participated in the Vial of Life Project; the implementation experience and
      student exposure to the implementation process. RESULTS: There were 12 residents
      out of 83 total who elected to receive the service from a pharmacist. This
      resulted in a 14.45% participation rate. In addition, the faculty and students
      were exposed to the program and its implementation in an independent living
      facility. CONCLUSION: The Vial of Life Project has allowed for increase in access
      to the pharmacist for education and medication reviews.

PMID- 22591980
TI  - HIV: a growing concern in the elderly population.
AB  - HIV infections are a growing concern in the elderly as a result of improvements
      in therapeutics and monitoring, which have extended the life span for this HIV
      infected population. Elderly patients potentially are more complicated to treat
      than younger HIV-infected individuals because of comorbidities and the
      physiological effects of aging on pharmacokinetics and pharmacodynamics. The
      patient, a 67-year-old African-American HIV-infected male, presents to the
      transitional care unit of university-affiliated hospital refusing to take
      medications and undergo laboratory testing, including blood draws. This patient's
      treatment is further complicated by poor renal function, medications with
      potential interactions, and a recent diagnosis of depression. This case
      demonstrates treatment and monitoring of an elderly patient with HIV and reveals
      the complications associated with this disease state. Specifically, it identifies
      nonadherence to medications and a lack of laboratory results, which affect the
      efficacy of treatment and monitoring, medication adjustments based on metabolism
      and renal excretion, monitoring of adverse effects of HIV and antiretroviral
      therapy, and comorbid conditions that may be linked to HIV and antiretroviral
      therapy such as depression and bone disease. Education on HIV medications,
      monitoring, and standards of care for pharmacists working with the geriatric
      population is warranted and should be emphasized as the HIV-infected elderly
      population continues to grow.

PMID- 22591981
TI  - Locating useful patient brochures and handouts.
AB  - Educational handouts are becoming routine in health care, helping promote health
      literacy in patients and their caregivers. To be effective, handouts must be
      tailored to various target audiences. This article discusses several Web sites
      that provide accurate information for conditions commonly seen in long-term care.

PMID- 22591982
TI  - Surgical treatment of paediatric cholesteatoma: long-term follow up in comparison
      with adults.
AB  - OBJECTIVE: This study was designed to analyse long-term results after surgery of
      acquired (ACH) and congenital cholesteatoma (CCH) of the middle ear in children
      and compare these with adults. METHODS: Computer-based analysis of consecutively
      operated paediatric patients for ACH and CCH in a tertiary referral centre was
      made in 57 cases under the age of 12 operated 1983-2004 by three surgeons using
      identical technique. A canal wall down and total reconstruction procedure (TRP)
      with obliteration of the mastoid cavity, canal wall reconstruction,
      ossiculoplasty with consistent use of autologous bone and an "aeration
      enhancement procedure" (AEP) with silicon sheet in selected cases were used. Pre-
      and post-operative PTA (0.5-3 kHz) and pure-tone average air-bone gap (PTA-ABG)
      together with surgical parameters were assessed 1, 3 and 6 years following
      surgery. RESULTS: Results showed stable hearing over 6 years with low incidence
      of persistent and recurrent disease comparable with results from adult patients.
      In nearly half of the cases, silastic sheeting was used. In 21 cases, stapes was
      eroded. Bone conduction thresholds levels remained unaffected 6 years after
      surgery. No deaf ears, postoperative facial dysfunction or other lesions related
      to surgery were observed. Six years after surgery every evaluated ear was found
      to be water-resistant and infection -free. CONCLUSION: Our results suggest that
      one-stage eradication of ACH and CCH in children using total reconstruction
      procedure (TRP) provide long-term improvement or preservation of hearing, with a
      low incidence of persistent or recurrent disease. No difference in surgical
      outcome between children and adults was found.

PMID- 22591983
TI  - Mandibular distraction osteogenesis in children with Pierre Robin sequence:
      impact on health-related quality of life.
AB  - BACKGROUND: Upper airway obstruction in children with Pierre Robin sequence (PRS)
      may be severe enough to require surgical intervention. Although many studies have
      demonstrated the effectiveness of mandibular distraction osteogenesis (MDO) in
      relieving airway obstruction, no study has reported health-related quality of
      life (QOL) outcomes. The objective of the present study was to conduct the first
      health-related QOL assessment post-MDO. METHODS: The Glasgow Children's Benefit
      Inventory (GCBI) questionnaire was distributed in a retrospective manner to the
      caregivers of all children who had undergone MDO at the authors' institutions
      between January 2007 and December 2010. Patients who had other major surgical
      procedures were excluded. RESULTS: The response rate was 84% (21 of 25
      questionnaires completed). The total mean GCBI score was +54 (SD, 19.5), which
      demonstrated a subjective overall benefit in health-related QOL post-MDO. All of
      the domains within the GCBI also scored in the positive range, indicating domain
      specific improvements in health-related QOL. There were no significant
      differences in the GCBI scores between syndromic-PRS patients and isolated PRS
      patients; similar results were observed between tracheostomy patients and no
      tracheostomy patients. SUMMARY: In treating children with PRS and severe upper
      airway obstruction, MDO resulted in a subjective overall benefit in health
      related QOL in our study population.

PMID- 22591984
TI  - Thymic epithelial cells: working class heroes for T cell development and
      repertoire selection.
AB  - The thymus represents an epithelial-mesenchymal tissue, anatomically structured
      into discrete cortical and medullary regions that contain phenotypically and
      functionally distinct stromal cells, as well as thymocytes at defined stages of
      maturation. The stepwise progression of thymocyte development seems to require
      serial migration through these distinct thymic regions, where interactions with
      cortical thymic epithelial cell (cTEC) and medullary thymic epithelial cell
      (mTEC) subsets take place. Recent work on TEC subsets provides insight into T
      cell development and selection, such as the importance of tumour necrosis factor
      (TNF) receptor superfamily members in thymus medulla development, and the
      specialised antigen processing/presentation capacity of the thymic cortex for
      positive selection. Here, we summarise current knowledge on the development and
      function of the thymic microenvironment, paying particular attention to the
      cortical and medullary epithelial compartments.

PMID- 22591985
TI  - Efficacy of treatments for orthostatic hypotension: a systematic review.
AB  - BACKGROUND: orthostatic hypotension (OH) affects up to 30% of adults over 65 and
      frequently contributes to falls and syncopal episodes. Current guidelines suggest
      a wide range of treatments, but systematic reviews of the evidence base for such
      recommendations are lacking. METHODS: we performed a systematic review to assess
      the evidence for all non-pharmacological and pharmacological interventions for
      OH. Our search included the following databases: MEDLINE; EMBASE; CINAHL; and the
      Cochrane library. We searched grey literature and references from included
      studies and other reviews. We included randomised, placebo-controlled trials,
      which measured postural drop as an outcome. Study quality was assessed using pre
      specified measures of bias. RESULTS: overall, 36 trials (21 interventions) were
      included. We identified a heterogeneous population and a wide variety of study
      methods, precluding meta-analysis. Most trials were of poor quality with high
      risk of bias. Changes in postural drop and symptoms were frequently inconsistent.
      Compression bandages, indomethacin, oxilofrine, potassium chloride and yohimbine
      improved the postural drop. Several vasoactive drugs-including midodrine and
      pyridostigmine-improved the standing blood pressure, but overall worsened the
      postural drop. CONCLUSIONS: many commonly recommended interventions for OH have a
      limited evidence base supporting their use. High quality, randomised, controlled
      trials are needed to underpin clinical practice for this condition.

PMID- 22591986
TI  - Hearing-impaired adults are at increased risk of experiencing emotional distress
      and social engagement restrictions five years later.
AB  - BACKGROUND: we aimed to assess both cross-sectional and temporal links between
      measured hearing impairment and self-perceived hearing handicap, and health
      outcomes. METHODS: in total, 811 Blue Mountains Hearing Study participants
      (Sydney, Australia) aged >=55 years were examined twice (1997-99 and 2002-04).
      Hearing levels were measured with pure-tone audiometry. The shortened version of
      the hearing handicap inventory (HHIE-S) was administered, scores >=8 defined
      hearing handicap. RESULTS: baseline hearing impairment was strongly associated
      with 7 of the 10 HHIE-S questions, 5 years later. Individuals with and without
      hearing impairment at baseline reported that they felt embarrassed and/or
      frustrated by their hearing problem, and that it hampered their personal/social
      life, multivariable-adjusted OR: 11.5 (CI: 3.5-38.1), OR: 6.3 (CI: 2.5-15.7) and
      OR: 6.0 (CI: 2.1-17.5), respectively, 5 years later. Hearing-impaired, compared
      with non-hearing-impaired adults had a significantly higher risk of developing
      moderate or severe hearing handicap, OR: 3.35 (CI: 1.91-5.90) and OR: 6.60 (CI:
      1.45-30.00), respectively. Cross-sectionally (at wave 2), hearing handicap
      increased the odds of depressive symptoms and low self-rated health by 80 and
      46%, respectively. CONCLUSION: older, hearing-impaired adults were significantly
      more likely to experience emotional distress and social engagement restrictions
      (self-perceived hearing handicap) directly due to their hearing impairment.

PMID- 22591987
TI  - Mitochondrial proticity and ROS signaling: lessons from the uncoupling proteins.
AB  - Fifty years since Peter Mitchell proposed the theory of chemiosmosis, the
      transformation of cellular redox potential into ATP synthetic capacity is still a
      widely recognized function of mitochondria. Mitchell used the term 'proticity' to
      describe the force and flow of the proton circuit across the inner membrane. When
      the proton gradient is coupled to ATP synthase activity, the conversion of fuel
      to ATP is efficient. However, uncoupling proteins (UCPs) can cause proton leaks
      resulting in poor fuel conversion efficiency, and some UCPs might control
      mitochondrial reactive oxygen species (ROS) production. Once viewed as toxic
      metabolic waste, ROS are now implicated in cell signaling and regulation. Here,
      we discuss the role of mitochondrial proticity in the context of ROS production
      and signaling.

PMID- 22591988
TI  - Effect of olive-mill waste addition to soil on sorption, persistence, and
      mobility of herbicides used in Mediterranean olive groves.
AB  - Laboratory and field experiments were conducted to evaluate the effect of olive
      mill waste (OMW) addition to a Mediterranean olive grove soil on sorption,
      persistence, and mobility of two herbicides which are simultaneously applied for
      weed control in olive groves: terbuthylazine (TA) and fluometuron (FM).
      Laboratory batch sorption experiments showed that OMW addition to the soil at
      rates of 5 and 10% (w/w) greatly enhanced the sorption of both herbicides, thus
      suggesting that amendment with OMW could be useful to enhance the retention and
      reduce the mobility of FM and TA in the soil. Incubation experiments showed that
      OMW increased the persistence of FM and had little effect on the long persistence
      of TA in the soil studied. A demonstration field experiment was also conducted in
      field plots with a slope of about 5%, either unamended or amended with OMW at a
      rate of 10 kg m-2, and then treated with a commercial formulation containing a
      mixture of TA and FM. Extraction of field soil samples, taken from different soil
      depths (0-5, 5-10, 10-20, and 20-30 cm) at different times after herbicide
      application, showed that both TA and FM moved deeper in unamended soil than in
      OMW-amended soil, and that OMW addition affected the persistence of FM in the
      toplayer, increasing its half-life from 24 to 58 days, while having little effect
      on the persistence of TA. Thus, data obtained under real field conditions were
      consistent with those obtained under controlled laboratory conditions.
      Preliminary herbicide runoff data indicated that the total herbicide runoff
      losses were also reduced upon OMW addition. Addition of OMW could be beneficial
      in reducing the mobility of TA and FM in olive grove soils, and also in
      increasing the persistence of FM in soils where this herbicide could be rapidly
      degraded.

PMID- 22591989
TI  - Soil components mitigate the antimicrobial effects of silver nanoparticles
      towards a beneficial soil bacterium, Pseudomonas chlororaphis O6.
AB  - Silver nanoparticles (Ag NPs) are widely used for their antimicrobial activity
      and consequently the particles will become environmental contaminants. This study
      evaluated in sand and soil matrices the toxicity of 10nm spherical Ag NPs (1 and
      3 mg Ag/L) toward a beneficial soil bacterium, Pseudomonas chlororaphis O6. In
      sand, both NP doses resulted in loss in bacterial culturability whereas in a loam
      soil, no cell death was observed. Amendments of sand with clays (30% v/v
      kaolinite or bentonite) did not protect the bacterium when challenged with Ag
      NPs. However, culturability of the bacterium was maintained when the Ag NP
      amended sand was mixed with soil pore water or humic acid. Imaging by atomic
      force microscopy revealed aggregation of single nanoparticles in water, and their
      embedding into background material when suspended in pore water and humic acids.
      Zeta potential measurements supported aggregation and surface charge
      modifications with pore water and humic acids. Measurement of soluble Ag in the
      microcosms and geochemical modeling to deduce the free ion concentration revealed
      bacterial culturability was governed by the predicted free Ag ion concentrations.
      Our study confirmed the importance of Ag NPs as a source of ions and illustrated
      that processes accounting for protection in soil against Ag NPs involved distinct
      NP- and ion-effects. Processes affecting NP bioactivity involved surface charge
      changes due to sorption of Ca2+ from the pore water leading to agglomeration and
      coating of the NPs with humic acid and other organic materials. Removal of
      bioactive ions included the formation of soluble Ag complexes with dissolved
      organic carbon and precipitation of Ag ions with chloride in pore water. We
      conclude that mitigation of toxicity of Ag NPs in soils towards a soil bacterium
      resides in several interactions that differentially involve protection from the
      Ag NPs or the ions they produce.

PMID- 22591990
TI  - Application of cluster analysis to surface ozone, NO2 and SO2 daily patterns in
      an industrial area in Central-Southern Spain measured with a DOAS system.
AB  - The daily variations of surface ozone, NO2 and SO2 have been investigated in a
      heavily industrialised area in the centre of the Iberian Peninsula (Puertollano)
      using hourly values recorded during two years (2008-2009) with an active LP-DOAS
      system. The meteorological conditions and air masses have been studied using the
      HYSPLIT model. The maximum hourly levels of these air pollutants exceeded 100 ppb
      for ozone, 150 ppb for SO2 and 210 ppb for NO2. However, mean values for ozone,
      NO2 and SO2 were of 49, 10 and 3 ppb respectively. Daily-monthly evolutions
      (defined as daily evolutions for different months) have been analysed in order to
      know the general daily behaviour of these species. Air pollution problems have
      been identified using the thresholds defined in the European Directive 2008. The
      limits to protect human health (human health protection limitations) have been
      exceeded during the study period. In order to find a set of representative daily
      cycles for each pollutant at different air quality regimes, a K-mean cluster
      technique has been applied. Five and four optimal cluster numbers have been
      obtained for the daily patterns of ozone and SO2 respectively. In addition, we
      studied the daily variation of the temperature, relative and specific humidity
      and wind speed associated with each air pollutant daily pattern. Ozone daily
      patterns showed typical daily variations with one exception of a cluster which
      presents a peak in the early morning. For SO2, the first two clusters present a
      low mixing ratio, however cluster 3 and 4 are less frequent but with higher
      levels. The more frequent air pollutant daily patterns do not exceed the
      threshold defined in the Directive. Nevertheless, clusters with lower frequency
      (representing between 5 and 7% of days) exceed the thresholds and could be
      considered as air pollution events.

PMID- 22591991
TI  - Vertical distribution of natural radionuclides in soil: assessment of external
      exposure of population in cultivated and undisturbed areas.
AB  - In the present work, naturally occurring radionuclides 238U, 232Th and 40K were
      measured in soil samples from the cultivated and undisturbed areas in Rudovci,
      municipality of Lazarevac, Serbia. There were three profiles, each profile
      divided into four horizons, giving the twelve soil samples. The specific activity
      of 238U, 232Th and 40K in soil and sediment samples was determined by gamma
      spectrometry using the HPGe semiconductor detector. Obtained activity
      concentrations ranged from 28.0 to 44.0 Bq/kg for 238U, from 59.4 to 71.4 Bq/kg
      for 232Th and from 335.0 to 517.0 Bq/kg for 40K. The evaluation of the
      radiological hazards originated from 238U, 232Th and 40K in the samples, the
      absorbed dose rate (D) and the annual effective dose rate (E), calculated in
      accordance with the UNSCEAR 2000 report, are presented in this paper.

PMID- 22591992
TI  - Increasing lake water and sediment oxygen levels using slow release peroxide.
AB  - The sediment and hypolimnion of many Finnish lakes suffer from anoxia due to
      increasing nutrient loading. The aim of this research was to develop a method for
      increasing the oxygen level using granulated calcium peroxide (CaO2) as a slow
      oxygen releasing compound. This compound releases oxygen (O2) in a reaction with
      water during 5 to 7 months. The method was tested in both laboratory and field
      conditions. In the field test granulated CaO2 were then spread manually from a
      rowing boat over the whole surface of the test pond. The granules sink onto and
      into the sediment. No mixing was needed. The dissolved oxygen concentration
      increased significantly during a laboratory experiment with a CaO2 amendment of
      75 g m-2 and in a pond experiment with a CaO2 amendment of 50 g m-2. In the pond
      experiment, the effect was visible for the entire 40-week experiment. In the
      laboratory, the abundance of aerobic bacteria increased in the sediment after
      CaO2 addition, while the pond experiment gave more mixed results. The organic
      matter content of the sediment did not change during the experiment in the
      control pond, but decreased from 18% to 4% in the pond with the CaO2 amendment.
      This was possibly due to enhanced microbial activity in the test pond. Although
      the results show improved oxygen concentrations and effects on the sediment
      organic matter following CaO2 amendment, the usability of this method in larger
      lakes remains to be tested.

PMID- 22591993
TI  - Urinary metabolites before and after cleanup and subjective symptoms in volunteer
      participants in cleanup of the Hebei Spirit oil spill.
AB  - BACKGROUND: On December 7th, 2007, the Hong Kong tanker Hebei Spirit (HS)
      (146,848 tons) was crushed by a crane ship near the shore of Taean, Korea. More
      than 12,547 kl of crude oil spilled into the sea and contaminated the western
      coastline of the Korean peninsula. For a period of six months after the accident,
      approximately 1,000,000 volunteers participated in the cleanup. Our goal in this
      study was to examine the exposure status and acute health effects on volunteers
      that participated in the oil spill cleanup. METHODS: A survey questionnaire was
      filled out by 565 volunteers, requesting information regarding physical symptoms.
      Out of the total number of participants, urine samples from 105 university
      student volunteers were collected before and after the cleanup work, and
      metabolite levels of volatile organic compounds and polycyclic aromatic
      hydrocarbons were analyzed. RESULTS: Volunteers that participated for longer
      cleanup work reported an increase in physical symptoms including visual
      disturbance, nasal and bronchus irritation, headaches, heart palpitations,
      fatigue and fever, memory and cognitive disturbance, and abdominal pain. The
      levels of t,t-muconic acid, mandelic acid, and 1-hydroxypyrene were significantly
      higher in samples after cleanup than those measured before participation
      (p<0.05). Other than the associated risk of dermal irritation with the difference
      in the t,t-muconic acid level between the post- to pre-cleanup levels, no other
      physical symptoms demonstrated a significant association with changes observed in
      the levels of urinary metabolites. CONCLUSIONS: Based on the significant increase
      of subjective symptoms in volunteers participating in the study, monitoring of
      the long term health effects, focusing on those with longer exposure, is
      warranted.

PMID- 22591994
TI  - Factitious hypoglycemia.

PMID- 22591995
TI  - [Primary hyperparathyroidism with osteitis fibrosa cystica mimicking a malignant
      bone tumor].

PMID- 22591996
TI  - Hypothesis for resolution of diabetes after sleeve gastrectomy.
AB  - Sleeve gastrectomy improves glucose metabolism as effective as Roux-en Y gastric
      bypass. The underlying mechanism is still not clear. We hypothesized that
      inhibition of GOAT activity was one therapeutic consequence of SG, and a status
      of low ghrelin level with low AG: UAG ratio might be an optimal gastrointestinal
      hormone profile for the remission of T2DM.

PMID- 22591997
TI  - Chromosomally-integrated human herpesvirus 6 in familial glioma etiology.
AB  - Human herpesvirus 6 (HHV-6) is a highly neurotropic beta-herpesvirus with
      demonstrated transformative properties. HHV-6 infection has been implicated in
      the etiologies of cancers, including lymphoma and leukemia; conditions with brain
      involvement, including epilepsy and encephalitis; and other disorders. HHV-6 is
      also the only human herpesvirus that has been proven to integrate into the
      chromosomes of a proportion (1-12%) of infected individuals. Because several
      traditional genetic association studies have failed to identify a variant that
      can account for the established relationship between family history and glioma
      risk, the possibility that chromosomally-integrated HHV-6 (CI-HHV-6), as a
      heritable factor, may explain a proportion of familial glioma cases warrants
      evaluation. To test this hypothesis, the prevalence of CI-HHV-6 in familial
      glioma cases and related and unrelated cancer-free control groups should be
      compared. Among glioma-affected families, the inheritance pattern of CI-HHV-6
      could be evaluated by constructing pedigrees. If CI-HHV-6 is found to be
      associated with familial glioma risk, this knowledge could potentially lead to
      the future development of novel therapeutic and preventive approaches, including
      vaccines and immunotherapies targeted at the HHV-6 sequences.

PMID- 22591998
TI  - Effects of the orientation of the 23Na-29Si dipolar vector on the dipolar
      mediated heteronuclear solid state NMR correlation spectrum of crystalline sodium
      silicates.
AB  - Dipolar-Heteronuclear Multiple Quantum Correlation (D-HMQC) experiment based on
      SR4(2)(1) recoupling was shown as a very efficient probe of spatial proximities
      in ordered or disordered materials. As crystalline sodium silicates have been
      extensively studied using 1D and 2D MAS NMR experiments and DFT calculations,
      they have been used as candidate model systems to perform this D-HMQC experiment.
      In this work, we demonstrate that the combination of (29)Si and (23)Na NMR at
      high magnetic field and DFT calculations makes it possible to revisit the
      assignment of the NMR signature of the delta-Na(2)Si(2)O(5) polymorph. A D-HMQC
      experiment performed on this crystalline sample reveals lineshape distortions on
      the (23)Na powder patterns extracted from the 2D correlation. Numerical
      simulations showed that these distortions result from an effect of the relative
      orientation between the (23)Na quadrupolar tensor and the (23)Na-(29)Si dipolar
      vector at the origin of the magnetization transfer.

PMID- 22591999
TI  - Positive associations between serum levels of IGF-I and subcutaneous fat depots
      in young men. The Odense Androgen Study.
AB  - INTRODUCTION: Serum levels of IGF-I are of growing interest due to the
      associations with morbidity and mortality. Despite markedly suppressed GH
      secretion, total IGF-I levels are often within normal range in obese adults. AIM:
      To study associations between IGF-I and estimated muscle mass in the Odense
      Androgen Study population and secondly to investigate associations between serum
      IGF-I and regional fat depots. METHOD: The Odense Androgen Study is a population
      based, cross-sectional study of 776 randomly selected men aged 20-29 years.
      Regional lean and fat mass were measured by dual-energy X-ray absorptiometry,
      whereas regional muscle and fat areas were assessed by magnetic resonance
      imaging. RESULTS: Age-adjusted IGF-I levels correlated significantly with
      different estimates of muscle mass (r-values between 0.15 and 0.19; p<0.001).
      Using multiple linear regression, serum IGF-I correlated positively with
      subcutaneous adipose tissue on the abdomen (SAT) after controlling for visceral
      adipose tissue (VAT) in the whole group and in the subgroup of men with normal
      waist circumference (r-values between 0.13 and 0.15; p<0.03). In addition, IGF-I
      correlated positively with subcutaneous thigh fat area (TFA) after controlling
      for intramyocellular lipid (imcl) r=0.18; p<0.004) and IGF-I correlated
      negatively with TFAimcl in the whole group and in the subgroup of men with normal
      waist circumference. CONCLUSION: SAT and subcutaneous TFAs were positively
      associated with IGF-I in regression analyses. Conversely, imcl of the thigh was
      inversely associated with IGF-I levels. These findings emphasize the differential
      associations between IGF-I and regional fat deposits. Future studies may provide
      further insight regarding the interplay between circulating IGF-I levels and
      regional muscle and fat mass.

PMID- 22592000
TI  - A 3 year national longitudinal study comparing drug treatment outcomes for opioid
      users with and without children in their custodial care at intake.
AB  - The aim of this research was to measure the longitudinal effects of having
      children in a client's custodial care, on opioid treatment outcomes. A 3 year
      national, longitudinal study was implemented. Outcomes were measured using the
      Maudsley Addiction Profile, 404 clients (75% male) were recruited and 97% were
      located at 3 years. At 1 year significantly fewer of those with children in their
      care were using heroin, benzodiazepines and cannabis but having children in a
      client's care at intake was a significant and positive predictor of using other
      opioids at 1 year. Analysis also revealed that there was a significant reduction
      in the proportion using alcohol in the last 90 days and in the mean days alcohol
      was used among those with no children in their care. Results demonstrate that
      having children in a client's care improves outcomes for heroin use but also
      suggest the possible use of substitution substances.

PMID- 22592001
TI  - Determination of oxidative stress in wheat leaves as influenced by boron toxicity
      and NaCl stress.
AB  - Boron (B) toxicity symptoms are visible in the form of necrotic spots and may
      worsen the oxidative stress caused by salinity. Hence, the interactive effects of
      combined salinity and B toxicity stress on antioxidative activities (TAC, LUPO,
      SOSA, CAT, and GR) were investigated by novel luminescence assays and standard
      photometric procedures. Wheat plants grown under hydroponic conditions were
      treated with 2.5 MUM H3BO3 (control), 75 mM NaCl, 200 MUM H3BO3, or 75 mM NaCl +
      200 MUM H3BO3, and analysed 6 weeks after germination. Shoot fresh weight (FW),
      shoot dry weight (DW), and relative water content (RWC) were significantly
      reduced, whereas the antioxidative activity of all enzymes was increased under
      salinity compared with the control. High B application led to necrotic leaf spots
      but did not influence growth parameters. Following NaCl + B treatment, shoot DW,
      RWC, SOSA, GR, and CAT activities remained the same compared with NaCl alone,
      whereas the TAC and LUPO activities were increased under the combined stress
      compared with NaCl alone. However, shoot FW was significantly reduced under NaCl
      + B compared with NaCl alone, as an additive effect of combined stress. Thus, we
      found an adjustment of antioxidative enzyme activity to the interactive effects
      of NaCl and high B. The stress factor "salt" mainly produced more oxidative
      stress than that of the factor "high B". Furthermore, addition of higher B in the
      presence of NaCl increases TAC and LUPO demonstrating that increased LUPO
      activity is an important physiological response in wheat plants against multiple
      stresses.

PMID- 22592002
TI  - A selective aryl hydrocarbon receptor modulator 3,3'-Diindolylmethane inhibits
      gastric cancer cell growth.
AB  - BACKGROUND: Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription
      factor associated with gastric carcinogenesis. 3,3'-Diindolylmethane (DIM) is a
      relatively non-toxic selective AhR modulator. This study was to detect the
      effects of DIM on gastric cancer cell growth. METHODS: Gastric cancer cell
      SGC7901 was treated with DIM at different concentrations (0,10,20,30,40,50
      MUmol/L) with or without an AhR antagonist, resveratrol. The expression of AhR
      and Cytochrome P4501A1 (CYP1A1), a classic target gene of AhR pathway, were
      detected by RT-PCR and Western blot; cell viability was measured by MTT assay,
      and the changes in cell cycle and apoptosis were analyzed by flow cytometry.
      RESULTS: RT-PCR and western-blot showed that with the increase of the
      concentration of DIM, AhR protein gradually decreased and CYP1A1 expression
      increased, suggesting that DIM activated the AhR pathway and caused the
      translocation of AhR from cytoplasm to nucleus. MTT assay indicated that the
      viability of SGC7901 cells was significantly decreased in a concentration- and
      time-dependent manner after DIM treatment and this could be partially reversed by
      resveratrol. Flow cytometry analysis showed that DIM arrested cell cycle in G1
      phase and induced cell apoptosis. CONCLUSION: Selective aryl hydrocarbon receptor
      modulator 3,3'-Diindolylmethane inhibits SGC7901 cell proliferation by inducing
      apoptosis and delaying cell cycle progression. AhR may be a potential therapeutic
      target for gastric cancer treatment.

PMID- 22592003
TI  - Nationwide surveillance study of human astrovirus infections in an Italian
      paediatric population.
AB  - The study investigated the genetic diversity of human astroviruses (HAstVs)
      detected in children hospitalized with gastroenteritis in Italy in 2008-2009. A
      total of 1321 faecal samples were collected in Parma (northern Italy), Bari
      (southern Italy), and Palermo (Sicily) and screened for the presence of HAstVs.
      RT-PCR amplification of a portion at the 5'-end of ORF2 allowed the detection of
      HAstVs in 3.95% of the patients. Four different genotypes (HAstV-1, HAstV-2,
      HAstV-4, HAstV-5) were found to be circulating during the study period, with
      HAstV-1 being the predominant type. Interestingly, a novel lineage, proposed as
      HAstV-2d, was found to have emerged in Parma in 2009. Investigating the genetic
      variability of HAstVs will be important for understanding the epidemiological
      trends and evolution of these viruses.

PMID- 22592004
TI  - Bell palsy in a neonate with rapid response to oral corticosteroids: a case
      report.
AB  - Idiopathic facial nerve palsy, also known as Bell palsy is rare in the neonatal
      age group. Other more common causes such as birth trauma; infections, especially
      otitis media; and congenital malformations need to be excluded. We present here a
      4-week-old neonate with Bell palsy who responded rapidly to oral corticosteroids.
      Such an early presentation of idiopathic facial nerve palsy and use of
      corticosteroids in neonates is scarcely reported in the literature.

PMID- 22592006
TI  - Protective Effects of Nigella sativa Oil in Hyperoxia-Induced Lung Injury.
AB  - BACKGROUND: Oxygen-induced lung injury is believed to lead to the development of
      bronchopulmonary dysplasia in premature infants. We have evaluated the beneficial
      effects of Nigella sativa oil (NSO) on rats with hyperoxia-induced lung injury.
      METHODS: Thirty newborn Sprague-Dawley rats were randomly divided into 3 groups
      as hyperoxia (95% O(2)), hyperoxia+NSO and control (21% O(2)). Pups in the
      hyperoxia+NSO group were administered intraperitoneal NSO at a dose of 4ml/kg
      daily during the study period. Histopathologic, immunochemical, and biochemical
      evaluations (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px],
      malonaldehyde [MDA] and myeloperoxidase [MPO]) were performed. RESULTS: In the
      histopathologic and immunochemical evaluation, severity of lung damage was
      significantly lower in the hyperoxia+NOS group (P<.05). Tissue GSH-Px and SOD
      levels were significantly preserved, and MDA, MPO levels were significantly lower
      in the hyperoxia+NSO group (P<.05). CONCLUSION: NSO significantly reduced the
      severity of lung damage due to hyperoxia.

PMID- 22592005
TI  - Systems immunology of human malaria.
AB  - Plasmodium falciparum malaria remains a global public health threat. Optimism
      that a highly effective malaria vaccine can be developed stems in part from the
      observation that humans can acquire immunity to malaria through experimental and
      natural P. falciparum infection. Recent advances in systems immunology could
      accelerate efforts to unravel the mechanisms of acquired immunity to malaria.
      Here, we review the tools of systems immunology, their current limitations in the
      context of human malaria research, and the human 'models' of malaria immunity to
      which these tools can be applied.

PMID- 22592007
TI  - Serial echocardiographic assessment of the human heart in normal pregnancy.

PMID- 22592008
TI  - Normal weight obesity: is bigger really badder?

PMID- 22592010
TI  - Imaging the coronary artery: is it really normal? How to avoid common
      echocardiographic pitfalls.

PMID- 22592009
TI  - Molecular imaging of aortic aneurysms.

PMID- 22592011
TI  - Molecular, cellular, and functional characterization of myocardial regions in
      hypertrophic cardiomyopathy.

PMID- 22592012
TI  - T1 mapping shows increased extracellular matrix size in the myocardium due to
      amyloid depositions.

PMID- 22592014
TI  - Letter by Ozkan regarding article, "low-flow, low-gradient severe aortic stenosis
      despite normal ejection fraction is associated with severe left ventricular
      dysfunction as assessed by speckle-tracking echocardiography: a multicenter
      study".

PMID- 22592016
TI  - Letter by Aquaro et al regarding article, "intermediate-signal-intensity late
      gadolinium enhancement predicts ventricular tachyarrhythmias in patients with
      hypertrophic cardiomyopathy".

PMID- 22592017
TI  - Association between physical activity and brain health in older adults.
AB  - In the present cross-sectional study, we examined physical activity (PA) and its
      possible association with cognitive skills and brain structure in 331 cognitively
      healthy elderly. Based on the number of self-reported light and hard activities
      for at least 30 minutes per week, participants were assigned to 4 groups
      representing different levels of PA. The cognitive skills were assessed by the
      Mini Mental State Examination score, a verbal fluency task, and the Trail-making
      test as a measure of visuospatial orientation ability. Participants also
      underwent a magnetic resonance imaging of the brain. Multiple regression analysis
      revealed that greater PA was associated with a shorter time to complete the Trail
      making test, and higher levels of verbal fluency. Further, the level of self
      reported PA was positively correlated with brain volume, white matter, as well as
      a parietal lobe gray matter volume, situated bilaterally at the precuneus. These
      present cross-sectional results indicate that PA is a lifestyle factor that is
      linked to brain structure and function in late life.

PMID- 22592018
TI  - Verbal learning in Alzheimer's disease and mild cognitive impairment: fine
      grained acquisition and short-delay consolidation performance and neural
      correlates.
AB  - The aim of this study was to examine correlations between acquisition and short
      delay consolidation and brain metabolism at rest measured by fluorodeoxyglucose
      positron emission tomography (FDG-PET) in 44 Alzheimer's disease (AD) patients,
      16 patients with mild cognitive impairment (MCI) who progressed to dementia (MCI
      AD), 15 MCI patients who remained stable (MCI-S, 4-8 years of follow-up), and 20
      healthy older participants. Acquisition and short-delay consolidation were
      calculated respectively as mean gained (MG) and lost (ML) access to items of the
      California Verbal Learning Task. MG performance suggests that acquisition is
      impaired in AD patients even at predementia stage (MCI-AD). ML performance
      suggests that short-delay consolidation is deficient only in confirmed AD
      patients. Variations in acquisition performance in control participants are
      related to metabolic activity in the anterior parietal cortex, an area supporting
      task-positive attentional processes. In contrast, the acquisition deficit is
      related to decreased activity in the lateral temporal cortex, an area supporting
      semantic processes, in patients at an early stage of AD and is related to
      metabolic activity in the hippocampus, an area supporting associative processes,
      in confirmed AD patients.

PMID- 22592019
TI  - p73 haploinsufficiency causes tau hyperphosphorylation and tau kinase
      dysregulation in mouse models of aging and Alzheimer's disease.
AB  - Haploinsufficiency for the p53 family member p73 causes behavioral and
      neuroanatomical correlates of neurodegeneration in aging mice, including the
      appearance of aberrant phospho-tau-positive aggregates. Here, we show that these
      aggregates and tau hyperphosphorylation, as well as a generalized dysregulation
      of the tau kinases GSK3beta, c-Abl, and Cdk5, occur in the brains of aged p73+/-
      mice. To investigate whether p73 haploinsufficiency therefore represents a
      general risk factor for tau hyperphosphorylation during neurodegeneration, we
      crossed the p73+/- mice with 2 mouse models of neurodegeneration, TgCRND8+/O mice
      that express human mutant amyloid precursor protein, and Pin1-/- mice. We show
      that haploinsufficiency for p73 leads to the early appearance of phospho-tau
      positive aggregates, tau hyperphosphorylation, and activation of GSK3beta, c-Abl,
      and Cdk5 in the brains of both of these mouse models. Moreover, p73+/-;TgCRND8+/O
      mice display a shortened lifespan relative to TgCRND8+/O mice that are wild type
      for p73. Thus, p73 is required to protect the murine brain from tau
      hyperphosphorylation during aging and degeneration.

PMID- 22592020
TI  - Liraglutide protects against amyloid-beta protein-induced impairment of spatial
      learning and memory in rats.
AB  - Type 2 diabetes mellitus is a risk factor of Alzheimer's disease (AD), most
      likely linked to an impairment of insulin signaling in the brain. Liraglutide, a
      novel long-lasting glucagon-like peptide 1 (GLP-1) analog, facilitates insulin
      signaling and shows neuroprotective properties. In the present study, we analyzed
      the effects of liraglutide on the impairment of learning and memory formation
      induced by amyloid-beta protein (Abeta), and the probable underlying
      electrophysiological and molecular mechanisms. We found that (1) bilateral
      intrahippocampal injection of Abeta(25-35) resulted in a significant decline of
      spatial learning and memory of rats in water maze tests, together with a serious
      depression of in vivo hippocampal late-phase long-term potentiation (L-LTP) in
      CA1 region of rats; (2) pretreatment with liraglutide effectively and dose
      dependently protected against the Abeta(25-35)-induced impairment of spatial
      memory and deficit of L-LTP; (3) liraglutide injection also activated cAMP signal
      pathway in the brain, with a nearly doubled increase in the cAMP contents
      compared with control. These results strongly suggest that upregulation of GLP-1
      signaling in the brain, such as application of liraglutide, may be a novel and
      promising strategy to ameliorate the learning and memory impairment seen in AD.

PMID- 22592021
TI  - Mean platelet volume is highly correlated to platelet count.

PMID- 22592022
TI  - Hyperthyroidism induced autoimmune myocarditis. Evaluation by cardiovascular
      magnetic resonance and endomyocardial biopsy.

PMID- 22592023
TI  - Melatonin and cardioprotection in the acute myocardial infarction: a promising
      cardioprotective agent.

PMID- 22592024
TI  - Left ventricular hypertrabeculation/non-compaction in a Duchenne/Becker muscular
      dystrophy carrier with epilepsy.

PMID- 22592025
TI  - Conservative management of left ventricle cardiac fibroma in an adult
      asymptomatic patient.

PMID- 22592026
TI  - Dynamic assessment of aortic annulus in patients with aortic stenosis throughout
      cardiac cycle with dual-source computed tomography.

PMID- 22592027
TI  - Comparison of single-plane and biplane area-length methods for right ventricular
      volume calculation: in vivo and vitro study.

PMID- 22592028
TI  - Statin therapy to reduce stent thrombosis in acute myocardial infarction patients
      with elevated high-sensitivity C-reactive protein.
AB  - OBJECTIVE: We investigated whether statin therapy and high-sensitivity C-reactive
      protein (hs-CRP) levels were associated with the risk of stent thrombosis (ST) in
      acute myocardial infarction (AMI) patients. METHODS: A total of 9,162 AMI
      patients who underwent coronary stent implantation were analyzed in the Korean
      Acute Myocardial Infarction Registry. The study population was divided into four
      groups according to level of hs-CRP and peri-procedural statin treatment: low hs
      CRP (<= 2.0mg/L) and high hs-CRP (>2mg/L) with or without statin therapy. We
      compared the incidence of early ST among the groups. RESULTS: Statin therapy did
      not significantly affect the development of early ST in the low hs-CRP group. In
      the high hs-CRP group, however, the incidence of early ST was significantly
      decreased with statin treatment. In a subgroup analysis of the high hs-CRP group,
      patients aged less than 65 years, without diabetes, with a high body mass index,
      and with a high Killip class seemed to benefit more from statin therapy. In a
      multivariable Cox regression analysis of the high hs-CRP group, lack of statin
      therapy was a significant predictor of ST incidence. CONCLUSIONS: Peri-procedural
      statin treatment had an effect on reduced incidence of early ST in AMI patients
      with high levels of hs-CRP.

PMID- 22592029
TI  - Normalization of left ventricle systolic function after resynchronization therapy
      in patients with dilated cardiomyopathy.

PMID- 22592030
TI  - Circulating osteoprotegerin and Dickkopf-1 changed significantly after surgical
      aortic valve replacement but remained without any significant differences after
      transcatheter aortic valve implantation.

PMID- 22592031
TI  - Aortic valve sclerosis is a marker of atherosclerosis independently of
      traditional clinical risk factors. Analysis in 712 patients without ischemic
      heart disease.

PMID- 22592032
TI  - Novel electrocardiographic findings related to new cardiac electronic devices
      functions.

PMID- 22592033
TI  - Atrial fibrillation as a consequence of tuberculous pericardial effusion.

PMID- 22592034
TI  - Inspiratory muscle training improves submaximal exercise capacity in patients
      with heart failure: a systematic review of randomized controlled trials.

PMID- 22592035
TI  - Triggering of supraventricular premature beats. The impact of acute and chronic
      risk factors.

PMID- 22592036
TI  - QT interval prolongation and bradycardia in lithium-induced nephrogenic diabetes
      insipidus.

PMID- 22592037
TI  - Dietary flaxseed oil reduces adipocyte size, adipose monocyte chemoattractant
      protein-1 levels and T-cell infiltration in obese, insulin-resistant rats.
AB  - BACKGROUND: Adipocyte dysfunction is characterized by an increase in adipocyte
      size and changes to their adipokine profiles. Immune cell infiltration into
      adipose tissue is thought to contribute to the metabolic complications of
      obesity, with local and systemic consequences for the inflammatory status of the
      obese individual. Dietary interventions with omega-3 fatty acids from marine
      sources have been successful at reducing inflammation. The aim of this study was
      to determine whether flaxseed oil containing the plant-based omega-3 fatty acid
      alpha-linolenic acid (ALA) is an effective modulator of inflammation and
      adipocyte dysfunction. METHODS: Seventeen-week old male fa/fa and lean Zucker
      rats were fed a control diet (faCTL, lnCTL) and fa/fa rats were fed an ALA-rich
      flaxseed oil supplemented diet (faFLAX) for 8 weeks. Adipose tissue and serum
      were collected and analyzed for cytokine (IL-6, IL-10, IL-18, IL-2, IFN-gamma,
      TNF-alpha), haptoglobin, monocyte chemoattractant protein-1 (MCP-1) and adipokine
      (leptin, adiponectin) levels. Splenocytes were isolated and ex vivo mitogen
      stimulated cytokine production was measured. Digital images of adipose tissue
      sections were used to quantify adipocyte area. Macrophage and T-cell infiltration
      were assessed in adipose tissue by immunohistochemistry. RESULTS: faFLAX rats had
      17% smaller adipocytes and 5-fold lower MCP-1 levels in adipose tissue than faCTL
      rats. Adipose tissue levels of IL-10 were 72% lower in the faFLAX group compared
      to baseline, and TNF-alpha levels decreased 80% (equal to lnCTL levels) in the
      faFLAX group compared to faCTL. There were no changes in ex vivo cytokine
      production by splenocytes between faFLAX and faCTL. Macrophage infiltration was
      not different among groups; however, faFLAX rats had less T-cell infiltration
      than faCTL rats. CONCLUSIONS: Dietary intervention with ALA-rich flaxseed oil in
      obese Zucker rats reduced adipocyte hypertrophy, protein levels of inflammatory
      markers MCP-1 and TNF-alpha, and T-cell infiltration in adipose tissue. Modest
      improvements to other parameters of obesity were also observed. The results
      suggest that, due to its ability to improve adipocyte function, ALA-rich flaxseed
      oil confers health benefits in obesity.

PMID- 22592038
TI  - Effect of inflammation on cytokine levels and bone remodelling markers in peri
      implant sulcus fluid: a preliminary report.
AB  - OBJECTIVES: Since ingredients of peri-implant sulcus fluid (PISF) may be related
      to the bony structure surrounding dental implants, analyze of specific markers
      related to bone resorption in PISF seems to be suitable for long term monitoring
      of peri-implant health. It is suggested that analysis of PISF may serve for
      detection of inflammation. The aim of this study is to analyze PISF interleukin-1
      beta (IL-1beta), IL-10, osteoprotegerin (OPG), receptor activator of nuclear
      factor-kappa B ligand (RANKL) levels to determine whether the diagnostic value of
      PISF can be used to evaluate early changes around implants. MATERIALS AND
      METHODS: A total of 47 dental implants either healthy/non-inflamed (n=20) (Group
      I), or gingivitis/inflamed (n=27) (Group II), were classified. Peri-implant
      status has been evaluated by clinical evaluation (plaque index, gingival index,
      probing depth and gingival bleeding time index) were recorded and PISF samples
      were also obtained. PISF IL-1beta, IL-10, RANKL, and OPG levels were measured by
      enzyme-linked immunosorbent assay. Potential volumetric changes in PISF were also
      evaluated. RESULTS: All clinical parameters and volume of PISF were higher in
      Group II and these differences were statistically significant except volume
      values. IL-1beta, IL-10 and OPG levels in PISF were significantly higher in Group
      II. Although the PISF RANKL level in Group II was higher than the level of Group
      I, the difference between groups did not reach the statistically significant
      level. CONCLUSIONS: These data suggest that a balance of inflammatory- and
      osteoclastogenesis related molecules locally produced may play an important role
      in the development of inflammatory peri-implant lesions.

PMID- 22592039
TI  - Diagnostic performance of serum interleukin-6 and interleukin-10 levels and
      clinical predictors in children with rotavirus and norovirus gastroenteritis.
AB  - OBJECTIVES: Rotavirus and norovirus are the two most common causes of acute viral
      gastroenteritis in children. This study aimed to explore the association of serum
      interleukin-6 (IL-6) and interleukin-10 (IL-10) levels and the clinical features
      in children with rotavirus and norovirus gastroenteritis. METHODS: This
      prospective study enrolled 168 acute gastroenteritis patients admitted to a
      tertiary care center. Peripheral blood samples were collected for IL-6 and IL-10
      assays within the first 72 h of illness. The diagnostic performance of clinical
      tests was estimated using the receiver operating characteristic (ROC) analysis.
      Binary logistic regression modeling was performed to examine the predictive
      variables. RESULTS: Serum IL-6 and IL-10 were measured in children with rotavirus
      infection (n=30), norovirus infection (n=25), Salmonella infection (n=26), and in
      11 healthy controls. There were significant higher degrees of severity of illness
      and levels of IL-10 in the rotavirus group as compared to the norovirus group.
      The binary logistic regression analysis revealed that both the ANC and maximum
      body temperature (BT) were significant clinical predictors for discriminating
      rotavirus and norovirus gastroenteritis. The ROC curve to evaluate the accuracy
      of logistic regression model had an AUC of 0.847 (95% CI: 0.741-0.952, p<0.001).
      CONCLUSIONS: IL-10 shows a significant discriminating ability between rotavirus
      and norovirus infection. A model incorporating maximum BT and ANC can help
      pediatricians to distinguish between rotavirus and norovirus in children with a
      suspected viral gastroenteritis.

PMID- 22592040
TI  - A randomized double-blind trial of upward progressive versus degressive
      compressive stockings in patients with moderate to severe chronic venous
      insufficiency.
AB  - BACKGROUND: The present randomized double-blind multicenter study was designed to
      assess the efficacy of a progressive compressive stocking (new concept with
      maximal pressure at calf), compared to a degressive compressive stocking graded
      30 mm Hg, evaluating the improvement of lower leg symptoms of chronic venous
      insufficiency (CVI) in ambulatory patients with moderate to severe chronic venous
      disease. METHODS: Both gender outpatients presenting symptomatic moderate to
      severe CVI were eligible for a treatment by compressive stockings. Patients were
      randomly assigned to receive either degressive compressive stockings (30 mm Hg at
      ankle, 21 mm Hg at upper calf) or progressive compressive stockings (10 mm Hg at
      ankle, 23 mm Hg at upper calf). The primary outcome, evaluated after 3 months,
      was a composite success outcome, including improvement of pain or heavy legs
      without onset of either ulcer, deep or superficial vein thrombosis of the lower
      limbs, or pulmonary embolism. The ease of application of the compressive
      stockings reported by patients was one of secondary outcome. RESULTS: Overall,
      401 patients (199 in the progressive compressive stocking group and 202 in the
      degressive compressive stocking group) were randomized by 44 angiologists in
      France. Among them, 66% were classified in the C3 CEAP category. The rate of
      success was significantly higher in the progressive compressive stocking group
      compared to the degressive compressive stocking group (70.0% vs 59.6%; relative
      risk, 1.18; 95% confidence interval, 1.02-1.37; P = .03). This was mainly due to
      more frequent symptom improvement in the progressive compressive stocking group.
      The compressive stockings were considered easy to apply by 81.3% of patients in
      the progressive compressive stocking group vs 49.7% of patients in the degressive
      compressive stocking group (P < .0001). The rate of related serious adverse
      events was low and similar in both groups. CONCLUSIONS: This trial has
      demonstrated that progressive compressive stockings are more effective than usual
      degressive compressive stockings in the improvement of pain and lower leg
      symptoms in patients with CVI. Moreover, progressive compressive stockings were
      easier to apply, raising no safety concern at 3 months.

PMID- 22592041
TI  - Lack of thrombus organization in nonshrinking aneurysms years after endovascular
      abdominal aortic aneurysm repair.
AB  - OBJECTIVE: During endovascular abdominal aortic aneurysm repair (EVAR), blood is
      trapped in the aneurysm sac at the moment the endograft is deployed. It is
      generally assumed that this blood will coagulate and evolve into an organized
      thrombus. It is unknown whether this process always occurs, what its time span
      is, and how it influences aneurysm shrinkage. With magnetic resonance imaging
      (MRI), quantitative analysis of the aneurysm sac is possible in terms of endoleak
      volume as well as unorganized thrombus volume and organized thrombus volume. We
      investigated the presence of unorganized thrombus in nonshrinking aneurysms years
      after EVAR. METHODS: Fourteen patients with a nonshrinking aneurysm without
      endoleak on computed tomography/computed tomography angiography underwent MRI
      with a blood pool agent (gadofosveset trisodium). Precontrast T1-, precontrast T2
      , and postcontrast T1-weighted images (3 and 30 minutes after injection) were
      acquired and evaluated for the presence of endoleak. The aneurysm sac was
      segmented into endoleak, unorganized thrombus, and organized thrombus by
      interactively thresholding the differently weighted images. The classification
      was visualized in real-time as a color overlay on the MR images. The volumes of
      endoleak, unorganized thrombus, and organized thrombus were calculated. RESULTS:
      Median time after EVAR was 2 years (range, 1-8.2 years). The average aneurysm sac
      volume of the patients was 167 +/- 107 mL (mean +/- standard deviation). Nine
      patients had an endoleak on the postcontrast T1-w images 30 minutes after
      injection. On average, the aneurysm sac contained 78 +/- 61 mL unorganized
      thrombus, which corresponded to 51 +/- 21 volume-percentage, irrespective of the
      presence of an endoleak on the blood pool agent enhanced MRI images (independent
      t-test, P = .8). CONCLUSIONS: In our study group, half of the nonshrinking
      aneurysm sac contents consisted of unorganized thrombus years after EVAR.

PMID- 22592042
TI  - Superior outcomes for rural patients after abdominal aortic aneurysm repair
      supports a systematic regional approach to abdominal aortic aneurysm care.
AB  - OBJECTIVE: The impact of geographic isolation on abdominal aortic aneurysm (AAA)
      care in the United States is unknown. It has been postulated but not proven that
      rural patients have less access to endovascular aneurysm repair (EVAR), vascular
      surgeons, and high-volume treatment centers than their urban counterparts,
      resulting in inferior AAA care. The purpose of this study was to compare the
      national experience for treatment of intact AAA for patients living in rural
      areas or towns with those living in urban areas. METHODS: Patients who underwent
      intact AAA repair in 2005 to 2006 were identified from a standard 5% random
      sample of all Medicare beneficiaries. Data on patient demographics,
      comorbidities, type of repair, and specialty of operating surgeon were collected.
      Hospitals were stratified into quintiles by yearly AAA volume. Primary outcomes
      included 30-day mortality and rehospitalization. RESULTS: A total of 2616
      patients had repair for intact AAA (40% open, 60% EVAR). Patients from rural and
      urban areas were equally likely to receive EVAR (rural 60% vs urban 61%; P = .99)
      and be treated by a vascular surgeon (rural 48% vs urban 50%; P = .82). Most
      rural patients (86%) received care in urban centers. Primary outcomes occurred in
      11.6% of rural patients (1.3% 30-day mortality; 10.3% rehospitalization) vs 16.0%
      of urban patients (3% 30-day mortality, 13% rehospitalization; P = .04). In
      multivariate analyses, rural residence was independently associated with
      treatment at high-volume centers (odds ratio, 1.64; 95% confidence interval, 1.34
      2.01; P < .0001) and decreased death or rehospitalization (odds ratio, 0.69; 95%
      confidence interval, 0.49-0.97; P = .03). CONCLUSIONS: Despite geographic
      isolation, patients in rural areas needing treatment for intact AAAs have
      equivalent access to EVAR and vascular surgeons, increased referral to high
      volume hospitals, and improved outcomes after repair. This suggests that urban
      patients may be disadvantaged even with nearby access to high-quality centers.
      This study supports the need for criteria that define centers of excellence to
      extend the benefit of regionalization to all patients.

PMID- 22592043
TI  - A one-step cone-beam CT-enabled planning-to-treatment model for palliative
      radiotherapy-from development to implementation.
AB  - PURPOSE: To develop a cone-beam computed tomography (CT)-enabled one-step
      simulation-to-treatment process for the treatment of bone metastases. METHODS AND
      MATERIALS: A three-phase prospective study was conducted. Patients requiring
      palliative radiotherapy to the spine, mediastinum, or abdomen/pelvis suitable for
      treatment with simple beam geometry (<=2 beams) were accrued. Phase A established
      the accuracy of cone-beam CT images for the purpose of gross tumor target volume
      (GTV) definition. Phase B evaluated the feasibility of implementing the cone-beam
      CT-enabled planning process at the treatment unit. Phase C evaluated the online
      cone-beam CT-enabled process for the planning and treatment of patients requiring
      radiotherapy for bone metastases. RESULTS: Eighty-four patients participated in
      this study. Phase A (n = 9) established the adequacy of cone-beam CT images for
      target definition. Phase B (n = 45) established the quality of treatment plans to
      be adequate for clinical implementation for bone metastases. When the process was
      applied clinically in bone metastases (Phase C), the degree of overlap between
      planning computed tomography (PCT) and cone-beam CT for GTV and between PCT and
      cone-beam CT for treatment field was 82% +/- 11% and 97% +/- 4%, respectively.
      The oncologist's decision to accept the plan under a time-pressured environment
      remained of high quality, with the cone-beam CT-generated treatment plan
      delivering at least 90% of the prescribed dose to 100% +/- 0% of the cone-beam CT
      planning target volume (PTV). With the assumption that the PCT PTV is the gold
      standard target, the cone-beam CT-generated treatment plan delivered at least 90%
      and at least 95% of dose to 98% +/- 2% and 97% +/- 5% of the PCT PTV,
      respectively. The mean time for the online planning and treatment process was
      32.7 +/- 4.0 minutes. Patient satisfaction was high, with a trend for superior
      satisfaction with the cone-beam CT-enabled process. CONCLUSIONS: The cone-beam CT
      enabled palliative treatment process is feasible and is ready for clinical
      implementation for the treatment of bone metastases using simple beam geometry,
      providing a streamlined one-step process toward palliative radiotherapy.

PMID- 22592044
TI  - No effect of the transforming growth factor beta1 promoter polymorphism C-509T on
      TGFB1 gene expression, protein secretion, or cellular radiosensitivity.
AB  - PURPOSE: To study whether the promoter polymorphism (C-509T) affects transforming
      growth factor beta1 gene (TGFB1) expression, protein secretion, and/or cellular
      radiosensitivity for both human lymphocytes and fibroblasts. METHODS AND
      MATERIALS: Experiments were performed with lymphocytes taken either from 124
      breast cancer patients or 59 pairs of normal monozygotic twins. We used 15 normal
      human primary fibroblast strains as controls. The C-509T genotype was determined
      by polymerase chain reaction-restriction fragment length polymorphism or TaqMan
      single nucleotide polymorphism (SNP) genotyping assay. The cellular
      radiosensitivity of lymphocytes was measured by G0/1 assay and that of
      fibroblasts by colony assay. The amount of extracellular TGFB1 protein was
      determined by enzyme-linked immunosorbent assay, and TGFB1 expression was
      assessed via microarray analysis or reverse transcription-polymerase chain
      reaction. RESULTS: The C-509T genotype was found not to be associated with
      cellular radiosensitivity, neither for lymphocytes (breast cancer patients,
      P=.811; healthy donors, P=.181) nor for fibroblasts (P=.589). Both TGFB1
      expression and TGFB1 protein secretion showed considerable variation, which,
      however, did not depend on the C-509T genotype (protein secretion: P=.879; gene
      expression: lymphocytes, P=.134, fibroblasts, P=.605). There was also no general
      correlation between TGFB1 expression and cellular radiosensitivity (lymphocytes,
      P=.632; fibroblasts, P=.573). CONCLUSION: Our data indicate that any association
      between the SNP C-509T of TGFB1 and risk of normal tissue toxicity cannot be
      ascribed to a functional consequence of this SNP, either on the level of gene
      expression, protein secretion, or cellular radiosensitivity.

PMID- 22592045
TI  - Identification and characterization of a small inhibitory peptide that can target
      DNA-PKcs autophosphorylation and increase tumor radiosensitivity.
AB  - PURPOSE: The DNA protein kinase catalytic subunit (DNA-PKcs) is one of the
      critical elements involved in the DNA damage repair process. Inhibition of DNA
      PKcs results in hypersensitivity to ionizing radiation (IR); therefore, this
      approach has been explored to develop molecular targeted radiosensitizers. Here,
      we aimed to develop small inhibitory peptides that could specifically target DNA
      PKcs autophosphorylation, a critical step for the enzymatic activation of the
      kinase in response to IR. METHODS AND MATERIALS: We generated several small
      fusion peptides consisting of 2 functional domains, 1 an internalization domain
      and the other a DNA-PKcs autophosphorylation inhibitory domain. We characterized
      the internalization, toxicity, and radiosensitization activities of the fusion
      peptides. Furthermore, we studied the mechanisms of the inhibitory peptides on
      DNA-PKcs autophosphorylation and DNA repair. RESULTS: We found that among several
      peptides, the biotin-labeled peptide 3 (BTW3) peptide, which targets DNA-PKcs
      threonine 2647 autophosphorylation, can abrogate IR-induced DNA-PKcs activation
      and cause prolonged gamma-H2AX focus formation. We demonstrated that BTW3
      exposure led to hypersensitivity to IR in DNA-PKcs-proficient cells but not in
      DNA-PKcs-deficient cells. CONCLUSIONS: The small inhibitory peptide BTW3 can
      specifically target DNA-PKcs autophosphorylation and enhance radiosensitivity;
      therefore, it can be further developed as a novel class of radiosensitizer.

PMID- 22592046
TI  - Risk of radiation retinopathy in patients with orbital and ocular lymphoma.
AB  - PURPOSE: Radiation retinopathy is a potential long-term complication of radiation
      therapy to the orbit. The risk of developing this adverse effect is dose
      dependent; however, the threshold is unclear. The aim of this study was to
      identify the risk of developing radiation retinopathy at increasing radiation
      doses. METHODS AND MATERIALS: A 40-year retrospective review was performed of
      patients who received external beam radiation therapy for ocular/orbital non
      Hodgkin lymphoma (NHL). RESULTS: Sixty-seven patients who had at least one
      ophthalmic follow-up examination were included in this study. Most patients (52%)
      were diagnosed with NHL involving the orbit. Patients received external beam
      radiation therapy at doses between 1886 and 5400 cGy (mean, 3033 +/- 782 cGy).
      Radiation retinopathy developed in 12% of patients, and the median time to
      diagnosis was 27 months (range, 15-241 months). The mean prescribed radiation
      dose in patients with retinopathy was 3309 +/- 585 cGy, and the estimated retinal
      dose (derived by reviewing the dosimetry) was 3087 +/- 1030 cGy. The incidence of
      retinopathy increased with dose. The average prescribed daily fractionated dose
      was higher in patients who developed retinopathy than in patients who did not
      (mean, 202 cGy vs 180 cGy, respectively; P = .04). More patients with radiation
      retinopathy had comorbid diabetes mellitus type 2 than patients without
      retinopathy (P = .015). In our study, the mean visual acuity of the eyes that
      received radiation was worse than that of the eyes that did not (P = .027). Other
      postradiotherapy ocular findings included keratitis (6%), dry eyes (39%), and
      cataract (33%). CONCLUSIONS: Radiation retinopathy, a known complication of
      radiotherapy for orbital tumors, relates to vascular comorbidities and dose.
      Higher total doses and larger daily fractions (> 180 cGy) appear to be related to
      higher rates of retinopathy. Future larger studies are required to identify a
      statistically significant threshold for the development of retinopathy.

PMID- 22592047
TI  - Role of positron emission tomography-computed tomography in the management of
      anal cancer.
AB  - PURPOSE: Pre- and post-treatment staging of anal cancer are often inaccurate. The
      role of positron emission tomograpy-computed tomography (PET-CT) in anal cancer
      is yet to be defined. The aim of the study was to compare PET-CT with CT scan,
      sentinel node biopsy results of inguinal lymph nodes, and anal biopsy results in
      staging and in follow-up of anal cancer. METHODS AND MATERIALS: Fifty-three
      consecutive patients diagnosed with anal cancer underwent PET-CT. Results were
      compared with computed tomography (CT), performed in 40 patients, and with
      sentinel node biopsy (SNB) (41 patients) at pretreatment workup. Early follow-up
      consisted of a digital rectal examination, an anoscopy, a PET-CT scan, and anal
      biopsies performed at 1 and 3 months after the end of treatment. Data sets were
      then compared. RESULTS: At pretreatment assessment, anal cancer was identified by
      PET-CT in 47 patients (88.7%) and by CT in 30 patients (75%). The detection rates
      rose to 97.9% with PET-CT and to 82.9% with CT (P=.042) when the 5 patients who
      had undergone surgery prior to this assessment and whose margins were positive at
      histological examination were censored. Perirectal and/or pelvic nodes were
      considered metastatic by PET-CT in 14 of 53 patients (26.4%) and by CT in 7 of 40
      patients (17.5%). SNB was superior to both PET-CT and CT in detecting inguinal
      lymph nodes. PET-CT upstaged 37.5% of patients and downstaged 25% of patients.
      Radiation fields were changed in 12.6% of patients. PET-CT at 3 months was more
      accurate than PET-CT at 1 month in evaluating outcomes after chemoradiation
      therapy treatment: sensitivity was 100% vs 66.6%, and specificity was 97.4% vs
      92.5%, respectively. Median follow-up was 20.3 months. CONCLUSIONS: In this
      series, PET-CT detected the primary tumor more often than CT. Staging of
      perirectal/pelvic or inguinal lymph nodes was better with PET-CT. SNB was more
      accurate in staging inguinal lymph nodes.

PMID- 22592048
TI  - Dose-effect relationship in chemoradiotherapy for locally advanced rectal cancer:
      a randomized trial comparing two radiation doses.
AB  - PURPOSE: Locally advanced rectal cancer represents a major therapeutic challenge.
      Preoperative chemoradiation therapy is considered standard, but little is known
      about the dose-effect relationship. The present study represents a dose
      escalation phase III trial comparing 2 doses of radiation. METHODS AND MATERIALS:
      The inclusion criteria were resectable T3 and T4 tumors with a circumferential
      margin of <=5 mm on magnetic resonance imaging. The patients were randomized to
      receive 50.4 Gy in 28 fractions to the tumor and pelvic lymph nodes (arm A) or
      the same treatment supplemented with an endorectal boost given as high-dose-rate
      brachytherapy (10 Gy in 2 fractions; arm B). Concomitant chemotherapy, uftoral
      300 mg/m2 and L-leucovorin 22.5 mg/d, was added to both arms on treatment days.
      The primary endpoint was complete pathologic remission. The secondary endpoints
      included tumor response and rate of complete resection (R0). RESULTS: The study
      included 248 patients. No significant difference was found in toxicity or
      surgical complications between the 2 groups. Based on intention to treat, no
      significant difference was found in the complete pathologic remission rate
      between the 2 arms (18% and 18%). The rate of R0 resection was different in T3
      tumors (90% and 99%; P=.03). The same applied to the rate of major response
      (tumor regression grade, 1+2), 29% and 44%, respectively (P=.04). CONCLUSIONS:
      This first randomized trial comparing 2 radiation doses indicated that the higher
      dose increased the rate of major response by 50% in T3 tumors. The endorectal
      boost is feasible, with no significant increase in toxicity or surgical
      complications.

PMID- 22592049
TI  - Predictors of toxicity after image-guided high-dose-rate interstitial
      brachytherapy for gynecologic cancer.
AB  - PURPOSE: To identify predictors of grade 3-4 complications and grade 2-4 rectal
      toxicity after three-dimensional image-guided high-dose-rate (HDR) interstitial
      brachytherapy for gynecologic cancer. METHODS AND MATERIALS: Records were
      reviewed for 51 women (22 with primary disease and 29 with recurrence) treated
      with HDR interstitial brachytherapy. A single interstitial insertion was
      performed with image guidance by computed tomography (n = 43) or magnetic
      resonance imaging (n = 8). The median delivered dose in equivalent 2-Gy fractions
      was 72.0 Gy (45 Gy for external-beam radiation therapy and 24 Gy for
      brachytherapy). Toxicity was reported according to the Common Toxicity Criteria
      for Adverse Events. Actuarial toxicity estimates were calculated by the Kaplan
      Meier method. RESULTS: At diagnosis, the median patient age was 62 years and the
      median tumor size was 3.8 cm. The median D90 and V100 were 71.4 Gy and 89.5%; the
      median D2cc for the bladder, rectum, and sigmoid were 64.6 Gy, 61.0 Gy, and 52.7
      Gy, respectively. The actuarial rates of all grade 3-4 complications at 2 years
      were 20% gastrointestinal, 9% vaginal, 6% skin, 3% musculoskeletal, and 2%
      lymphatic. There were no grade 3-4 genitourinary complications and no grade 5
      toxicities. Grade 2-4 rectal toxicity was observed in 10 patients, and grade 3-4
      complications in 4; all cases were proctitis with the exception of 1 rectal
      fistula. D2cc for rectum was higher for patients with grade 2-4 (68 Gy vs 57 Gy
      for grade 0-1, P=.03) and grade 3-4 (73 Gy vs 58 Gy for grade 0-2, P=.02) rectal
      toxicity. The estimated dose that resulted in a 10% risk of grade 2-4 rectal
      toxicity was 61.8 Gy (95% confidence interval, 51.5-72.2 Gy). DISCUSSION: Image
      guided HDR interstitial brachytherapy results in acceptable toxicity for women
      with primary or recurrent gynecologic cancer. D2cc for the rectum is a reliable
      predictor of late rectal complications. Three-dimensional-based treatment
      planning should be performed to ensure adequate tumor coverage while minimizing
      the D2cc to the rectum.

PMID- 22592051
TI  - Characterizing glucose changes antecedent to hypoglycemic events in the intensive
      care unit.
AB  - OBJECTIVE: To determine whether patterns of glucose changes before hypoglycemia
      vary according to the severity of the event. METHODS: In this retrospective
      analysis, point-of-care blood glucose (POC-BG) data were obtained from the
      intensive care units (ICUs) of a convenience sample of hospitals that responded
      to a survey on inpatient diabetes management quality improvement initiatives. To
      evaluate POC-BG levels before hypoglycemic events, data from patients who
      experienced hypoglycemia during their time in the ICU were examined, and their
      glucose changes were assessed against a comparison group of patients who achieved
      a glycemic range of 80 to 110 mg/dL without ever experiencing hypoglycemia.
      Absolute glucose decrease, glucose rate of change, and glucose variability before
      hypoglycemic events (<40, 40-49, 50-59, and 60-69 mg/dL) were calculated.
      RESULTS: A total of 128,419 POC-BG measurements from 2942 patients in 89 ICUs
      were analyzed. Patients who experienced the most severe hypoglycemic episodes had
      the largest absolute drop in their glucose levels before the event (P<.001). The
      glucose rate of change before a hypoglycemic event increased with worsening
      hypoglycemia: mean (+/-standard deviation) glucose rate of change was -1.69 (+/
      2.98) mg/dL per min before an episode with glucose values less than 40 mg/dL, 
      0.56 (+/-2.65) mg/dL per min before an episode with glucose values 60 to 69
      mg/dL, but only -0.39 (+/-0.70) for patients who attained a glucose range of 80
      to 110 mg/dL without hypoglycemia (P<.001). Glucose variability before an event
      progressively increased with worsening biochemical hypoglycemia and was least
      among patients achieving glucose concentrations in the 80 to 110-mg/dL range
      without hypoglycemia (P<.001). CONCLUSIONS: Antecedent glucose change and
      variability were greater for patients who experienced hypoglycemia. If monitored,
      these patterns could potentially alert clinicians and help them take preventive
      measures. Further examination of how these parameters interact with other
      predisposing risk factors for hypoglycemia is warranted.

PMID- 22592050
TI  - Dose escalation of total marrow irradiation with concurrent chemotherapy in
      patients with advanced acute leukemia undergoing allogeneic hematopoietic cell
      transplantation.
AB  - PURPOSE: We have demonstrated that toxicities are acceptable with total marrow
      irradiation (TMI) at 16 Gy without chemotherapy or TMI at 12 Gy and the reduced
      intensity regimen of fludarabine/melphalan in patients undergoing hematopoietic
      cell transplantation (HCT). This article reports results of a study of TMI
      combined with higher intensity chemotherapy regimens in 2 phase I trials in
      patients with advanced acute myelogenous leukemia or acute lymphoblastic leukemia
      (AML/ALL) who would do poorly on standard intent-to-cure HCT regimens. METHODS
      AND MATERIALS: Trial 1 consisted of TMI on Days -10 to -6, etoposide (VP16) on
      Day -5 (60 mg/kg), and cyclophosphamide (CY) on Day -3 (100 mg/kg). TMI dose was
      12 (n=3 patients), 13.5 (n=3 patients), and 15 (n=6 patients) Gy at 1.5 Gy twice
      daily. Trial 2 consisted of busulfan (BU) on Days -12 to -8 (800 MUM min), TMI on
      Days -8 to -4, and VP16 on Day -3 (30 mg/kg). TMI dose was 12 (n=18) and 13.5
      (n=2) Gy at 1.5 Gy twice daily. RESULTS: Trial 1 had 12 patients with a median
      age of 33 years. Six patients had induction failures (IF), and 6 had first
      relapses (1RL), 9 with leukemia blast involvement of bone marrow ranging from 10%
      98%, 5 with circulating blasts (24%-85%), and 2 with chloromas. No dose-limiting
      toxicities were observed. Eleven patients achieved complete remission at Day 30.
      With a median follow-up of 14.75 months, 5 patients remained in complete
      remission from 13.5-37.7 months. Trial 2 had 20 patients with a median age of 41
      years. Thirteen patients had IF, and 5 had 1RL, 2 in second relapse, 19 with
      marrow blasts (3%-100%) and 13 with peripheral blasts (6%-63%). Grade 4 dose
      limiting toxicities were seen at 13.5 Gy (stomatitis and hepatotoxicity).
      Stomatitis was the most frequent toxicity in both trials. CONCLUSIONS: TMI dose
      escalation to 15 Gy is possible when combined with CY/VP16 and is associated with
      acceptable toxicities and encouraging outcomes. TMI dose escalation is not
      possible with BU/VP16 due to dose-limiting toxicities. Future efforts will focus
      on whether further dose escalation with CY/VP16 is safe, with the goal of
      improving disease control in this high-risk population.

PMID- 22592053
TI  - Visual vignette. Seckel syndrome.

PMID- 22592052
TI  - Visual vignette. Suppurative thyroiditis due to Nocardia asteroides.

PMID- 22592054
TI  - Visual vignette. Subglottic tracheal stenosis.

PMID- 22592055
TI  - Visual vignette. Thyrotroph cell hyperplasia.

PMID- 22592056
TI  - Alzheimer's disease genes and cognition in the nondemented general population.
AB  - BACKGROUND: Genome-wide association studies have established 11 genes for late
      onset Alzheimer's disease (AD). We investigated whether these genes jointly
      affect cognition in a nondemented population and improve prediction of AD.
      METHODS: In 5171 nondemented people (age 45-99 years) from the population-based
      Rotterdam Study, we genotyped APOE-epsilon4 and single nucleotide polymorphisms
      from the genes CLU, PICALM, BIN1, CR1, ABCA7, MS4A6A, MS4A4E, CD2AP, EPHA1, and
      CD33. We constructed a genetic risk score by adding the risk alleles per
      individual weighted by the reported effect sizes. All people underwent cognitive
      testing. With linear regression we investigated the relationship between the
      genetic risk score and cognition, with and without APOE. In a subcohort, with
      more than 10 years of follow-up, we assessed whether the risk score predicted AD.
      RESULTS: The genetic risk score was primarily associated with memory
      (standardized difference [95% confidence interval] per SD increase in genetic
      risk score: -.05[-.07; -.02], p = 1.5 * 10(-4)). This association attenuated when
      APOE was excluded from the genetic risk score (-.03[-.05; .00], p = .047) and
      would not survive a multiple-testing correction. Similarly, we found that
      although the genetic risk score without APOE was associated with the development
      of AD (p = .010), it only marginally improved prediction of AD beyond age, sex,
      APOE (area under the curve: .8159 vs. .8148). CONCLUSIONS: In nondemented people,
      there is only a marginal joint effect of AD genes on memory independent from
      APOE. Moreover, although associated with AD, these genes jointly hardly improve
      prediction of AD.

PMID- 22592057
TI  - Reduced dorsal anterior cingulate cortical activity during emotional regulation
      and top-down attentional control in generalized social phobia, generalized
      anxiety disorder, and comorbid generalized social phobia/generalized anxiety
      disorder.
AB  - BACKGROUND: Generalized social phobia (GSP) and generalized anxiety disorder
      (GAD) are both associated with emotion dysregulation. Research implicates dorsal
      anterior cingulate cortex in both explicit emotion regulation (EER) and top-down
      attentional control (TAC). Although studies have examined these processes in GSP
      or GAD, no work compares findings across the two disorders or examines
      functioning in cases comorbid for both disorders (GSP/GAD). Here we compare the
      neural correlates of EER and TAC in GSP, GAD, and GSP/GAD. METHODS: Medication
      free adults with GSP (EER n = 19; TAC n = 18), GAD (EER n = 17; TAC n = 17),
      GSP/GAD (EER n = 17; TAC n = 15), and no psychopathology (EER n = 18; TAC n = 18)
      participated. During EER, individuals alternatively viewed and upregulated and
      downregulated responses to emotional pictures. During TAC, they performed an
      emotional Stroop task. RESULTS: For both tasks, significant group * condition
      interactions emerged in dorsal anterior cingulate cortex and parietal cortices.
      Healthy adults showed significantly increased recruitment during emotion
      regulation, relative to emotion-picture viewing. GAD, GSP, and GSP/GAD subjects
      showed no such increases, with all groups differing from healthy adults but not
      from each other. Evidence of emotion-related disorder-specificity emerged in
      medial prefrontal cortex and amygdala. This disorder-specific responding varied
      as a function of emotion content but not emotion-regulatory demands. CONCLUSIONS:
      GSP and GAD both involve reduced capacity for engaging emotion-regulation brain
      networks, whether explicitly or via TAC. A reduced ability to recruit regions
      implicated in top-down attention might represent a general risk factor for
      anxiety disorders.

PMID- 22592058
TI  - Deletion of CREB-regulated transcription coactivator 1 induces pathological
      aggression, depression-related behaviors, and neuroplasticity genes dysregulation
      in mice.
AB  - BACKGROUND: Mood disorders are polygenic disorders in which the alteration of
      several susceptibility genes results in dysfunctional mood regulation. However,
      the molecular mechanisms underlying their transcriptional dysregulation are still
      unclear. The transcription factor cyclic adenosine monophosphate (cAMP) response
      element binding protein (CREB) and the neurotrophin brain-derived neurotrophic
      factor (BDNF) have been implicated in rodent models of depression. We previously
      provided evidence that Bdnf expression critically rely on a potent CREB
      coactivator called CREB-regulated transcription coactivator 1 (CRTC1). METHODS:
      To further evaluate the role of CRTC1 in the brain, we generated a knockout mouse
      line and analyzed its behavioral and molecular phenotype. RESULTS: We found that
      mice lacking CRTC1 associate neurobehavioral endophenotypes related to mood
      disorders. Crtc1(-/-) mice exhibit impulsive aggressiveness, social withdrawal,
      and decreased sexual motivation, together with increased behavioral despair,
      anhedonia, and anxiety-related behavior in the novelty-induced hypophagia test.
      They also present psychomotor retardation as well as increased emotional response
      to stressful events. Crtc1(-/-) mice have a blunted response to the
      antidepressant fluoxetine in behavioral despair paradigms, whereas fluoxetine
      normalizes their aggressiveness and their behavioral response in the novelty
      induced hypophagia test. Crtc1(-/-) mice strikingly show, in addition to a
      reduced dopamine and serotonin turnover in the prefrontal cortex, a concomitant
      decreased expression of several susceptibility genes involved in neuroplasticity,
      including Bdnf, its receptor TrkB, the nuclear receptors Nr4a1-3, and several
      other CREB-regulated genes. CONCLUSIONS: Collectively, these findings support a
      role for the CRTC1-CREB pathway in mood disorders etiology and behavioral
      response to antidepressants and identify CRTC1 as an essential coactivator of
      genes involved in mood regulation.

PMID- 22592059
TI  - Microbial induced lipoprotein biosurfactant from slaughterhouse lipid waste and
      its application to the removal of metal ions from aqueous solution.
AB  - This study aims at demonstrating the production of lipoprotein biosurfactant from
      Pseudomonas gessardii using goat tallow, a slaughterhouse lipid waste, as the
      substrate and its application to the removal of metal ions from aqueous solution.
      The maximum bio-transformation of goat tallow into biosurfactant occurred at 48
      h. The mass of the lipoprotein biosurfactant produced was 2.03 g/g of goat
      tallow. The biosurfactant was clearly characterized by surface tension, critical
      micelle concentration, emulsification index and molecular weight. The amino acid
      and fatty acid moieties of the biosurfactant were determined using High
      performance liquid chromatography (HPLC) and Gas chromatography (GC). The thermal
      behavior studies were evaluated using Thermo gravimetric (TG) and Differential
      scanning calorimetry (DSC) analysis. The lipoprotein biosurfactant was loaded
      onto the mesoporous activated carbon (MAC) for the sequestering of metal ions
      from the aqueous solution. The biosurfactant exhibited a removal efficiency for
      metal ions from aqueous solution in the order Cr(3+)>Ca(2+)>Cu(2+)>Fe(2+). The
      morphological observations and functional groups of the lipoprotein biosurfactant
      and that of the lipoprotein biosurfactant bound metal ions were determined using
      scanning electron micrograph (SEM) images and Fourier transform infrared (FT-IR)
      spectroscopy, respectively. This is the first report on the production of
      lipoprotein biosurfactant by P. gessardii using goat tallow as the substrate to
      sequester the metal ions from the aqueous solution.

PMID- 22592060
TI  - Capturing ambulatory activity decline in Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: Relatively little is known about the natural evolution of
      physical activity-related participation restrictions associated with Parkinson's
      disease (PD). We examined this issue prospectively, using continuous monitoring
      technology to capture the free-living ambulatory activity of persons with PD
      engaging in life situations. We specifically sought (1) to explore natural, long
      term changes in daily ambulatory activity and (2) to compare the responsiveness
      of ambulatory activity parameters to clinical measures of gait and disease
      severity. METHODS: Thirty-three persons with PD participated (Hoehn and Yahr
      range of 1-3). Participants wore a step activity monitor for up to 7 days at
      baseline and again at 1-year follow-up. Mean daily values were calculated for
      parameters indicative of amount, intensity, frequency, and duration of ambulatory
      activity. Clinical measures included the Unified Parkinson Disease Rating Scale,
      the 6-Minute Walk, and Maximal Gait Speed. Parametric tests for paired samples
      were used to investigate changes in ambulatory activity parameters and clinical
      measures. RESULTS: Participants had significant declines in the amount and
      intensity of daily ambulatory activity but not in its frequency and duration (P <
      0.007). Declines occurred in the absence of changes in clinical measures of gait
      or disease severity. The greatest 1-year decline occurred in the number of daily
      minutes participants spent engaging in at least moderate-intensity ambulatory
      activity. CONCLUSION: Continuous monitoring of ambulatory activity beyond mere
      step counts may serve as a distinct and important means of quantifying declining
      ambulatory behavior associated with disease progression or improved ambulatory
      behavior resulting from rehabilitation and medical and/or surgical interventions
      in persons with PD.

PMID- 22592061
TI  - Robotic assessment of sensorimotor deficits after traumatic brain injury.
AB  - BACKGROUND AND PURPOSE: Robotic technology is commonly used to quantify aspects
      of typical sensorimotor function. We evaluated the feasibility of using robotic
      technology to assess visuomotor and position sense impairments following
      traumatic brain injury (TBI). We present results of robotic sensorimotor function
      testing in 12 subjects with TBI, who had a range of initial severities (9 severe,
      2 moderate, 1 mild), and contrast these results with those of clinical tests. We
      also compared these with robotic test outcomes in persons without disability.
      METHODS: For each subject with TBI, a review of the initial injury and
      neuroradiologic findings was conducted. Following this, each subject completed a
      number of standardized clinical measures (Fugl-Meyer Assessment, Purdue Peg
      Board, Montreal Cognitive Assessment, Rancho Los Amigos Scale), followed by two
      robotic tasks. A visually guided reaching task was performed to assess visuomotor
      control of the upper limb. An arm position-matching task was used to assess
      position sense. Robotic task performance in the subjects with TBI was compared
      with findings in a cohort of 170 person without disabilities. RESULTS: Subjects
      with TBI demonstrated a broad range of sensory and motor deficits on robotic
      testing. Notably, several subjects with TBI displayed significant deficits in one
      or both of the robotic tasks, despite normal scores on traditional clinical motor
      and cognitive assessment measures. DISCUSSION AND CONCLUSIONS: The findings
      demonstrate the potential of robotic assessments for identifying deficits in
      visuomotor control and position sense following TBI. Improved identification of
      neurologic impairments following TBI may ultimately enhance rehabilitation.

PMID- 22592062
TI  - Monitoring community mobility with global positioning system technology after a
      stroke:  a case study.
AB  - BACKGROUND: Stroke survivors often experience difficulty returning to activities
      and places they deem important to their social, leisure, and occupational
      aspirations. The extent to which stroke survivors return to community mobility
      and their ability to navigate and access locations they deem meaningful have not
      been objectively measured. PURPOSE: We used global positioning system technology
      (GPSt) to measure the community mobility of a person poststroke, and assess the
      relationship between GPSt measures and clinical measures of mobility. METHODS: :
      The participant was a 56-year-old man who sustained a right pontine stroke. At
      discharge from rehabilitation, his Six-Minute Walk Test distance was 73 m. He was
      fitted with a GPS unit and an accelerometer attached to a single belt and
      instructed to wear the devices at all times when out of bed. After identifying 10
      locations that were important to his goals, he was monitored for 5 separate 1
      week periods, on the first, fifth, and ninth weeks and at 6 and 12 months after
      discharge. RESULTS: During the first 10 weeks, he averaged 7.6 target visits
      (70%) and 26.7 trips per week. At 1 year, his Six-Minute Walk distance score was
      287.5 m. Accelerometry data revealed that he remained primarily sedentary. Target
      visits and trips per week did not change substantially over the course of 1 year,
      and compliance wearing the GPS unit was variable. CONCLUSIONS: Given the limited
      correlation in gait speed and distance with target attainment and trips, these
      outcomes likely measure different constructs for this subject. GPSt may offer
      insights into participation for stroke survivors following rehabilitation.

PMID- 22592066
TI  - Ethical issues in brain-computer interface research, development, and
      dissemination.
AB  - The steadily growing field of brain-computer interfacing (BCI) may develop useful
      technologies, with a potential impact not only on individuals, but also on
      society as a whole. At the same time, the development of BCI presents significant
      ethical and legal challenges. In a workshop during the 4th International BCI
      meeting (Asilomar, California, 2010), six panel members from various BCI
      laboratories and companies set out to identify and disentangle ethical issues
      related to BCI use in four case scenarios, which were inspired by current
      experiences in BCI laboratories. Results of the discussion are reported in this
      article, touching on topics such as the representation of persons with
      communication impairments, dealing with technological complexity and moral
      responsibility in multidisciplinary teams, and managing expectations, ranging
      from an individual user to the general public. Furthermore, we illustrate that
      where treatment and research interests conflict, ethical concerns arise. On the
      basis of the four case scenarios, we discuss salient, practical ethical issues
      that may confront any member of a typical multidisciplinary BCI team. We
      encourage the BCI and rehabilitation communities to engage in a dialogue, and to
      further identify and address pressing ethical issues as they occur in the
      practice of BCI research and its commercial applications.

PMID- 22592064
TI  - Transcranial magnetic stimulation for the prediction and enhancement of
      rehabilitation treatment effects.
AB  - In this update on rehabilitation technology, transcranial magnetic stimulation
      (TMS), a technique that allows noninvasive stimulation of the brain, is examined.
      The background and basic principles of TMS are reviewed, and its usefulness as a
      tool to inform and possibly augment the rehabilitation process is discussed. The
      three main paradigms by which TMS is applied-physiological measurement,
      disruption/virtual lesion studies, and modulation of cortical excitability-are
      discussed relative to the types of scientific information each paradigm can
      provide and their potential clinical usefulness in the future. One of the more
      exciting prospects is that, when combined with rehabilitation training, TMS
      modulation of cortical excitability could potentially enhance the effects of
      rehabilitation and lead to greater levels of recovery than are currently
      attainable with rehabilitation alone. It is concluded that current studies must
      focus on the mechanisms of recovery based on the specific structures and
      processes affected by the disorder and the neural effects of specific
      rehabilitation interventions in order for the potential of TMS-augmented
      rehabilitation to be realized.

PMID- 22592063
TI  - Robots integrated with virtual reality simulations for customized motor training
      in a person with upper extremity hemiparesis:  a case study.
AB  - BACKGROUND AND PURPOSE: A majority of studies examining repetitive task practice
      facilitated by robots for the treatment of upper extremity paresis utilize
      standardized protocols applied to large groups. Others utilize interventions
      tailored to patients but do not describe the clinical decision-making process
      utilized to develop and modify interventions. This case study describes a robot
      based intervention customized to match the goals and clinical presentation of
      person with upper extremity hemiparesis secondary to stroke. METHODS: The
      patient, P.M., was an 85-year-old man with left hemiparesis secondary to an
      intracerebral hemorrhage 5 years prior to examination. Outcomes were measured
      before and after a 1-month period of home therapy and after a 1-month robotic
      intervention. The intervention was designed to address specific impairments
      identified during his physical therapy examination. When necessary, activities
      were modified on the basis of response to the first week of treatment. OUTCOMES:
      P.M. trained in 12 sessions, using six virtually simulated activities.
      Modifications to original configurations of these activities resulted in
      performance improvements in five of these activities. P.M. demonstrated a 35
      second improvement in Jebsen Test of Hand Function time and a 44-second
      improvement in Wolf Motor Function Test time subsequent to the robotic training
      intervention. Reaching kinematics, 24-hour activity measurement, and scores on
      the Hand and Activities of Daily Living scales of the Stroke Impact Scale all
      improved as well. DISCUSSION: A customized program of robotically facilitated
      rehabilitation was associated with short-term improvements in several
      measurements of upper extremity function in a patient with chronic hemiparesis.

PMID- 22592068
TI  - Why neuroplasticity?

PMID- 22592067
TI  - Identifying activity levels and steps of people with stroke using a novel shoe
      based sensor.
AB  - BACKGROUND/PURPOSE: Advances in sensor technologies provide a method to
      accurately assess activity levels of people with stroke in their community. This
      information could be used to determine the effectiveness of rehabilitation
      interventions as well as provide behavior-enhancing feedback. The purpose of this
      study was to assess the accuracy of a novel shoe-based sensor system (SmartShoe)
      to identify different functional postures and steps in people with stroke. The
      SmartShoe system consists of five force-sensitive resistors built into a flexible
      insole and an accelerometer on the back of the shoe. Pressure and acceleration
      data are sent via Bluetooth to a smart phone. METHODS: Participants with stroke
      wore the SmartShoe while they performed activities of daily living (ADLs) in
      sitting, standing, and walking positions. Data from four participants were used
      to develop a multilayer perceptron artificial neural network (ANN) to identify
      sitting, standing, and walking. A signal-processing algorithm used data from the
      pressure sensors to estimate the number of steps taken while walking. The
      accuracy, precision, and recall of the ANN for identifying the three functional
      postures were calculated with data from a different set of participants.
      Agreement between steps identified by SmartShoe and actual steps taken was
      analyzed by the Bland Altman method. RESULTS: The SmartShoe was able to
      accurately identify sitting, standing, and walking. Accuracy, precision, and
      recall were all greater than 95%. The mean difference between steps identified by
      SmartShoe and actual steps was less than one step. DISCUSSION: The SmartShoe was
      able to accurately identify different functional postures, using a unique
      combination of pressure and acceleration data, of people with stroke as they
      performed different ADLs. There was a strong level of agreement between actual
      steps taken and steps identified by the SmartShoe. Further study is needed to
      determine whether the SmartShoe could be used to provide valid information on
      activity levels of people with stroke while they go about their daily lives in
      their home and community.

PMID- 22592069
TI  - [Passion, concern and hope in caring for children].

PMID- 22592070
TI  - Does maternal use of tenofovir during pregnancy affect growth of HIV-exposed
      uninfected infants?

PMID- 22592071
TI  - Baseline E138 reverse transcriptase resistance-associated mutations in
      antiretroviral-naive HIV-infected patients.

PMID- 22592072
TI  - Toll-like receptor-2 ligand lipomannan from Mycobacterium tuberculosis does not
      stimulate inflammatory cytokines in dendritic cells.

PMID- 22592074
TI  - Hepatitis E infection is an under recognized cause of acute decompensation in
      patients with chronic liver disease.
AB  - BACKGROUND/AIMS: We aimed to assess characteristics of patients with a positive
      hepatitis E virus serology with emphasis on acute on chronic liver disease.
      METHODS: This was a retrospective audit performed at a large teaching hospital.
      RESULTS: Of the 164 patients tested, 15(9.1%) had a positive serology (hepatitis
      E virus IgG and or IgM) of whom two also had a positive hepatitis E virus RNA.
      Six (42.8%) had underlying chronic liver disease and presented with deteriorating
      liver tests+/-decompensation. In one patient (16%) acute hepatitis E virus
      infection was the aetiology for the decompensation and in three the positive
      hepatitis E virus IgG was a reflection of prior subclinical infection. However,
      in two of the six patients with unexplained decompensation there was delay (150
      270 days) in obtaining a hepatitis E virus serology, which may have resulted in a
      negative hepatitis E virus IgM at time of testing. CONCLUSIONS: 9.1% of patients
      presenting with abnormal liver tests at a large teaching hospital in south east
      England have a positive hepatitis E virus serology of whom 42.8% have acute on
      chronic liver disease. In 16% hepatitis E virus infection is the aetiology for
      the acute decompensation. This may be an under representation as in >30% of
      patients with unexplained decompensation there is considerable delay in
      requesting a hepatitis E virus serology.

PMID- 22592075
TI  - Electrophysiological correlates of enhanced perceptual processes and attentional
      capture by emotional faces in social anxiety.
AB  - Behavioural studies have used spatial cueing designs extensively to investigate
      emotional biases in individuals exhibiting clinical and sub-clinical anxiety.
      However, the neural processes underlying the generation of these biases remain
      largely unknown. In this study, people who scored unusually high or low on scales
      of social anxiety performed a spatial cueing task. They were asked to
      discriminate the orientation of arrows appearing at the location previously
      occupied by a lateralised cue (consisting of a face displaying an emotional or a
      neutral expression) or at the empty location. The results showed that the
      perceptual encoding of faces, indexed by P1, and mobilisation of attentional
      resources, reflected in P2 on occipital locations, were modulated by social
      anxiety. These modulations were directly linked to the social anxiety level but
      not to trait anxiety. By contrast, later cognitive stages and behavioural
      performances were not modulated by social anxiety, supporting the theory of
      dissociation between efficiency and effectiveness in anxiety.

PMID- 22592076
TI  - Neural correlates supporting sensory discrimination after left hemisphere stroke.
AB  - BACKGROUND: Nearly half of stroke patients have impaired sensory discrimination,
      however, the neural structures that support post-stroke sensory function have not
      been described. OBJECTIVES: 1) To evaluate the role of the primary somatosensory
      (S1) cortex in post-stroke sensory discrimination and 2) To determine the
      relationship between post-stroke sensory discrimination and structural integrity
      of the sensory component of the superior thalamic radiation (sSTR). METHODS: 10
      healthy adults and 10 individuals with left hemisphere stroke participated.
      Stroke participants completed sensory discrimination testing. An fMRI was
      conducted during right, impaired hand sensory discrimination. Fractional
      anisotropy and volume of the sSTR were quantified using diffusion tensor
      tractography. RESULTS: Sensory discrimination was impaired in 60% of participants
      with left stroke. Peak activation in the left (S1) did not correlate with sensory
      discrimination ability, rather a more distributed pattern of activation was
      evident in post-stroke subjects with a positive correlation between peak
      activation in the parietal cortex and discrimination ability (r=.70, p=.023). The
      only brain region in which stroke participants had significantly different
      cortical activation than control participants was the precuneus. Region of
      interest analysis of the precuneus across stroke participants revealed a positive
      correlation between peak activation and sensory discrimination ability (r=.77,
      p=.008). The L/R ratio of sSTR fractional anisotropy also correlated with right
      hand sensory discrimination (r=.69, p=.027). CONCLUSIONS: Precuneus cortex,
      distributed parietal lobe activity, and microstructure of the sSTR support
      sensory discrimination after left hemisphere stroke.

PMID- 22592078
TI  - Effect of a DNA vaccine harboring two copies of inhibin alpha (1-32) fragments on
      immune response, hormone concentrations and reproductive performance in rats.
AB  - The objective was to investigate the effects of a novel DNA vaccine (pcISI)
      harboring two copies of inhibin alpha (1-32) fragments on immune response,
      hormone concentrations and reproductive performance in rats. Female Wistar rats
      (n=18 per group) were immunized (twice, 4 wk apart) with 10, 50, or 100 MUg (T1,
      T2 and T3, respectively), of the pcISI plasmid. At 4 wk after the second
      immunization, plasma antibody titers were higher (P<0.05) in T3 than in either T1
      or T2 (0.341+/-0.123, 0.236+/-0.068, and 0.251+/-0.077, respectively, mean+/-SD).
      Concurrrently, plasma concentrations of FSH and estradiol were highest (P<0.05)
      in T3, and were higher (P<0.05) in T1 and T2 than in control groups. For antibody
      positive rats, there was a correlation (P<0.01) between antibody titer and FSH
      concentrations after two pcISI immunizations. The number of mature follicles in
      the T3 group (46.00+/-4.65) was higher (P<0.05) than in two control groups
      (29.25+/-3.72 and 27.92+/-3.48), and also higher (P<0.05) than in T1 and T2
      (37.17+/-4.99 and 38.75+/-7.09). Antibody-positive rats had more mature ovarian
      follicles than negative rats (46.75+/-4.23 vs. 35.60+/-3.38, P<0.05). Moreover,
      litter size and number of placentas were increased (P<0.05) in the pcISI
      immunization groups, except for the T1 group, compared to the control groups. In
      conclusion, the pcISI DNA vaccine successfully induced a humoral immune response,
      improved reproductive hormone concentrations, stimulated follicular development,
      and increased number of placentas and litter size. Furthermore, 100 MUg yielded
      the best immune response.

PMID- 22592077
TI  - The immunosuppressive factors IL-10, TGF-beta, and VEGF do not affect the antigen
      presenting function of CD40-activated B cells.
AB  - BACKGROUND: Progress in recent years strengthened the concept of cellular tumor
      vaccinations. However, a crucial barrier to successful cancer immunotherapy is
      tumor-mediated immunosuppression. Tumor-derived soluble factors such as IL-10,
      TGF-beta, and VEGF suppress effector cells either directly or indirectly by
      disruption of dendritic cell (DC) differentiation, migration and antigen
      presentation. Human B cells acquire potent immunostimulatory properties when
      activated via CD40 and have been shown to be an alternative source of antigen
      presenting cells (APCs) for cellular cancer vaccines. Nevertheless, in contrast
      to DCs little knowledge exists about their susceptibility to tumor derived
      immunosuppressive factors. Thus, we assessed whether IL-10, TGF-beta, or VEGF do
      affect key aspects of the immunostimulatory function of human CD40-activated B
      cells. METHODS: Cell surface expression of adhesion and costimulatory molecules
      and the proliferation capacity of CD40-activated B cells were compared to
      untreated controls by flow cytometry. Migration towards important chemokines of
      secondary lymph organs was measured with or without exposure to the
      immunosuppressive cytokines. Finally, an influence on T cell stimulation was
      investigated by allogeneic mixed lymphocyte reactions. For statistical analysis
      Student's t test or two-way analysis of variance followed by Bonferroni's post
      hoc test was used to compare groups. P values of <0.05 were considered
      statistically significant. RESULTS: Neither cell adhesion nor the expression of
      MHC class II and costimulatory molecules CD80 and CD86 was inhibited by addition
      of IL-10, TGF-beta, or VEGF. Likewise, the proliferation of CD40-activated B
      cells was not impaired. Despite being exposed to IL-10, TGF-beta, or VEGF the B
      cells migrated equally well as untreated controls to the chemokines SLC and SDF
      1alpha. Most importantly, the capacity of CD40-activated B cells to stimulate
      CD4+ and CD8+ T cells remained unaffected. CONCLUSION: Our findings suggest that
      key immunostimulatory functions of CD40-activated B cells are resistant to
      inhibition by the immunosuppressive factors IL-10, TGF-beta, and VEGF. This
      supports considerations to use ex vivo generated CD40-activated B cells as a
      promising alternative or additional APC for cellular immunotherapy, especially in
      settings where these immunosuppressive cytokines are present in tumor
      environment.

PMID- 22592079
TI  - [Risk of malnutrition in people older than 75 years].
AB  - BACKGROUND AND OBJECTIVES: Population aging has emerged as a major demographic
      trend worldwide. The objective of the present research was to study the risk of
      malnutrition in elderly patients older than 75 years that lived without relatives
      younger than them, and also to understand the effect of sex and age on
      nutritional status, as well as the anthropometric resulting values. SUBJECTS AND
      METHODS: A total of 63 patients older than 75 years were studied. The nutritional
      status was evaluated using the Mini Nutritional Assessment test. RESULTS:
      Overall, 22% of the studied population presented a high risk of malnutrition.
      Although the sex did not affect the nutritional status of studied patients, the
      age significantly influenced it. CONCLUSIONS: Patients older than 81 years
      demonstrated a greater risk of malnutrition, suggesting the necessity of
      personalized nutrition strategies to improve their quality of life and reduce the
      prevalence of related-diseases.

PMID- 22592080
TI  - [Factors associated with hospitalization in a cohort of elderly patients included
      in a home care program].
AB  - BACKGROUND AND OBJECTIVE: The objective is to identify the features associated
      with next year hospital admissions among elderly dependent patients living at
      home (EDLH) and visited by primary care teams at their home setting. PATIENTS AND
      METHOD: Longitudinal cohort study of a sample of EDLH patients admitted to a home
      care programme delivered by 72 primary care teams. A global health assessment was
      performed at recruitment in all patients (health and social status, informal and
      formal carer characteristics and burden of care). We further collected data on
      visits by primary care personnel and the use of social, emergency and hospital
      services by EDLH patients throughout one year after recruitment. RESULTS: A
      sample of 1,093 EDLH patients was included. 258 (23,6%) patients were admitted to
      hospital during follow-up and 170 (15.6%) were lost to follow-up. Hospitalised
      patients received the same volume of primary care and social care services at
      home than those that were not hospitalised. Independent predictors of high risk
      of hospital admission were calling and using the after-hours emergency community
      services (odds ratio [OR]= 2.50, 95% confidence interval [95% CI] 1.56-4.01) and
      comorbidity as measured by the Charlson Index (OR= 1.16, 95% CI 1.06-1.27) at
      recruitment. Similarly, female sex (OR= 0.59, 95% CI 0.40-0.85) and high
      subjective physical health status scores as measured by the SF12 questionnaire
      (OR 0.97, 95% CI 0.95-0.99) predicted a low-risk of hospital admission.
      CONCLUSIONS: Hospital admission among EDLH patients is related to comorbidity,
      gender, subjective health status and the use of uncoordinated emergency services
      as measured at recruitment, rather than to the use of services during the one
      year follow-up.

PMID- 22592081
TI  - High-resolution melting analysis of 15 genes in 60 patients with cytochrome-c
      oxidase deficiency.
AB  - Cytochrome-c oxidase (COX) deficiency is one of the common childhood
      mitochondrial disorders. Mutations in genes for the assembly factors SURF1 and
      SCO2 are prevalent in children with COX deficiency in the Slavonic population.
      Molecular diagnosis is difficult because of the number of genes involved in COX
      biogenesis and assembly. The aim of this study was to screen for mutations in 15
      nuclear genes that encode the 10 structural subunits, their isoforms and two
      assembly factors of COX in 60 unrelated Czech children with COX deficiency. Nine
      novel variants were identified in exons and adjacent intronic regions of COX4I2,
      COX6A1, COX6A2, COX7A1, COX7A2 and COX10 using high-resolution melting (HRM)
      analysis. Online bioinformatics servers were used to predict the importance of
      the newly identified amino-acid substitutions. The newly characterized variants
      updated the contemporary spectrum of known genetic sequence variations that are
      present in the Czech population, which will be important for further targeted
      mutation screening in Czech COX-deficient children. HRM and predictive
      bioinformatics methodologies are advantageous because they are low-cost screening
      tools that complement large-scale genomic studies and reduce the required time
      and effort.

PMID- 22592082
TI  - A cautionary note on the reporting of genetic association study results.

PMID- 22592083
TI  - Platelet usage trends in a tertiary care hospital - Could it be less and less
      expensive?
AB  - Major bleeding is a life threatening complication of severe thrombocytopenia. The
      aim of this study was to find out the indications and the threshold for platelet
      transfusions in the pediatric patients of our hospital throughout 1 year. Records
      of the hospital's blood bank and the files of the patients were retrospectively
      reviewed. One hundred and four patients, between ages 0-18 years received 378
      platelet units. Pretransfusion platelet counts were found to be significantly
      lower in hematology-oncology groups compared to other clinics (p<0.05). Single
      donor apheresis was found to be the major source of platelets in hematology
      (80.8%, n=147) and oncology (86.5%, n=45) clinics. There is a tendency for using
      apheresis products without proven superiority compared to platelet concentrates
      in terms of efficacy. This practice can be abandoned by continuous education.

PMID- 22592084
TI  - Luffa echinata Roxb. induces human colon cancer cell (HT-29) death by triggering
      the mitochondrial apoptosis pathway.
AB  - The antiproliferative properties and cell death mechanism induced by the extract
      of the fruits of Luffa echinata Roxb. (LER) were investigated. The methanolic
      extract of LER inhibited the proliferation of human colon cancer cells (HT-29) in
      both dose-dependent and time-dependent manners and caused a significant increase
      in the population of apoptotic cells. In addition, obvious shrinkage and
      destruction of the monolayer were observed in LER-treated cells, but not in
      untreated cells. Analysis of the cell cycle after treatment of HT-29 cells with
      various concentrations indicated that LER extracts inhibited the cellular
      proliferation of HT-29 cells via G2/M phase arrest of the cell cycle. The
      Reactive oxygen species (ROS) level determination revealed that LER extracts
      induced apoptotic cell death via ROS generation. In addition, LER treatment led
      to a rapid drop in mitochondrial membrane potential (MMP) as a decrease in
      fluorescence. The transcripts of several apoptosis-related genes were
      investigated by RT-PCR analysis. The caspase-3 transcripts of HT-29 cells
      significantly accumulated and the level of Bcl-XL mRNA was decreased after
      treatment with LER extract. Furthermore, the ratio of mitochondria-dependent
      apoptosis genes (Bax and Bcl-2) was sharply increased from 1.6 to 54.1. These
      experiments suggest that LER has anticancer properties via inducing the apoptosis
      in colon cancer cells, which provided the impetus for further studies on the
      therapeutic potential of LER against human colon carcinoma.

PMID- 22592085
TI  - A new facile synthesis of d4-pterosin B and d4-bromopterosin, deuterated
      analogues of ptaquiloside.
AB  - Ptaquiloside (Pta) is a potent carcinogen present in bracken fern and in soil
      matrices, that can potentially leach to the aquatic environment. More recently
      its presence in the milk of different farm animals has been reported. Pterosin B
      (Ptb) and bromopterosin (BrPt) represent the most convenient analogues in the
      detection of ptaquiloside by mass spectrometry. Pterosin sesquiterpenes are also
      involved in many patented biomedical protocols. In this work we introduce a new
      and convenient approach to the synthesis in three steps and more than 80% yield
      of d4-pterosin B (d4-Ptb) and d4-bromopterosin (d4-BrPt), useful as internal
      standards in the quantification of ptaquiloside.

PMID- 22592086
TI  - A study of proline metabolism in canola (Brassica napus L.) seedlings under salt
      stress.
AB  - Expression analysis of crop plants has improved our knowledge about the veiled
      underlying mechanisms for salt tolerance. In order to observe the time course
      effects of salinity stress on gene expression for enzymes regulating proline
      metabolism, we comparatively analyzed the expression of specific genes for
      proline metabolism in root and shoot tissues of salt-tolerant (cv. Dunkled) and
      salt-sensitive (cv. Cyclone) canola (Brassica napus L.) cultivars through reverse
      transcriptase polymerase chain reaction (RT-PCR); following the NaCl treatment
      for various durations. Both lines showed an increase in ?1-pyrroline-5
      carboxylate synthase1 (P5CS1) gene expression after induction of salt stress with
      enhanced expression in the root tissue of the tolerant line, while maximum
      expression was noted in the shoot tissues of the sensitive line. We observed a
      much reduced proline dehydrogenase (PDH) expression in both the root and shoot
      tissues of both canola lines, with more marked reduction of PDH expression in the
      shoot tissues than that in the root ones. To confirm the increase in P5CS1 gene
      expression, total proline content was also measured in the root and shoot tissues
      of both the canola lines. The root tissues of canola sensitive line showed a
      gradually increasing proline concentration pattern with regular increase in
      salinity treatment, while an increase in proline concentration in the tolerant
      line was noted at 24 h post salinity treatment after a sudden decrease at 6 h and
      12 h of salt treatment. A gradually increasing concentration of free proline
      content was found in shoot tissues of the tolerant canola line though a
      remarkable increase in proline concentration was noted in the sensitive canola
      line at 24 h post salinity treatment, indicating the initiation of proline
      biosynthesis process in that tissue of sensitive canola.

PMID- 22592087
TI  - Recent advances in photoinduced electron transfer processes of fullerene-based
      molecular assemblies and nanocomposites.
AB  - Photosensitized electron-transfer processes of fullerenes hybridized with
      electron donating or other electron accepting molecules have been surveyed in
      this review on the basis of the recent results reported mainly from our
      laboratories. Fullerenes act as photo-sensitizing electron acceptors with respect
      to a wide variety of electron donors; in addition, fullerenes in the ground state
      also act as good electron acceptors in the presence of light-absorbing electron
      donors such as porphyrins. With single-wall carbon nanotubes (SWCNTs), the
      photoexcited fullerenes act as electron acceptor. In the case of triple
      fullerene/porphyrin/SWCNT architectures, the photoexcited porphyrins act as
      electron donors toward the fullerene and SWCNT. These mechanisms are rationalized
      with the molecular orbital considerations performed for these huge
      supramolecules. For the confirmation of the electron transfer processes,
      transient absorption methods have been used, in addition to time-resolved
      fluorescence spectral measurements. The kinetic data obtained in solution are
      found to be quite useful to predict the efficiencies of photovoltaic cells.

PMID- 22592088
TI  - Chemical investigation of saponins in different parts of Panax notoginseng by
      pressurized liquid extraction and liquid chromatography-electrospray ionization
      tandem mass spectrometry.
AB  - A pressurized liquid extraction (PLE) and high performance liquid chromatography
      electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method was
      developed for the qualitative determination of saponins in different parts of P.
      notoginseng, including rhizome, root, fibre root, seed, stem, leaf and flower.
      The samples were extracted using PLE. The analysis was achieved on a Zorbax SB
      C18 column with gradient elution of acetonitrile and 8 mM aqueous ammonium
      acetate as mobile phase. The mass spectrometer was operated in the negative ion
      mode using the electrospray ionization, and a collision induced dissociation
      (CID) experiment was also carried out to aid the identification of compounds.
      Forty one saponins were identified in different parts of P. notoginseng according
      to the fragmentation patterns and literature reports, among them, 21 saponins
      were confirmed by comparing the retention time and ESI-MS data with those of
      standard compounds. The results showed that the chemical characteristics were
      obviously diverse in different parts of P. notoginseng, which is helpful for
      pharmacological evaluation and quality control of P. notoginseng.

PMID- 22592089
TI  - Effects of Citrus aurantium (bitter orange) fruit extracts and p-synephrine on
      metabolic fluxes in the rat liver.
AB  - The fruit extracts of Citrus aurantium (bitter orange) are traditionally used as
      weight-loss products and as appetite supressants. An important fruit component is
      p-synephrine, which is structurally similar to the adrenergic agents. Weight-loss
      and adrenergic actions are always related to metabolic changes and this work was
      designed to investigate a possible action of the C. aurantium extract on liver
      metabolism. The isolated perfused rat liver was used to measure catabolic and
      anabolic pathways, including oxygen uptake and perfusion pressure. The C.
      aurantium extract and p-synephrine increased glycogenolysis, glycolysis, oxygen
      uptake and perfusion pressure. These changes were partly sensitive to alpha- and
      beta-adrenergic antagonists. p-Synephrine (200 MUM) produced an increase in
      glucose output that was only 15% smaller than the increment caused by the extract
      containing 196 MUM p-synephrine. At low concentrations the C. aurantium extract
      tended to increase gluconeogenesis, but at high concentrations it was inhibitory,
      opposite to what happened with p-synephrine. The action of the C. aurantium
      extract on liver metabolism is similar to the well known actions of adrenergic
      agents and can be partly attributed to its content in p-synephrine. Many of these
      actions are catabolic and compatible with the weight-loss effects usually
      attributed to C. aurantium.

PMID- 22592090
TI  - Design, synthesis and antiproliferative activity of novel 2-substituted-4-amino-6
      halogenquinolines.
AB  - Two series of novel 2-substituted-4-amino-6-halogenquinolines 8a-l and 13a-h were
      designed, synthesized and evaluated for their antiproliferative activity against
      H-460, HT-29, HepG2 and SGC-7901 cancer cell lines in vitro. The pharmacological
      results indicated that most compounds with 2-arylvinyl substituents exhibited
      good to excellent antiproliferative activity. Among them, compound 8e was a
      considered promising lead for further structural modifications with IC50 values
      of 0.03 MUM, 0.55 MUM, 0.33 MUM and 1.24 MUM, which was 2.5- to 186-fold more
      active than gefitinib and compound 1.

PMID- 22592091
TI  - Synthesis of 1,2,3-triazole derivatives and in vitro antifungal evaluation on
      Candida strains.
AB  - 1,2,3-Triazoles have been extensively studied as compounds possessing important
      biological activities. In this work, we describe the synthesis of ten 2-(1-aryl
      1H-1,2,3-triazol-4-yl)propan-2-ols via copper catalyzed azide alkyne
      cycloaddition (CuAAc or click chemistry). Next the in vitro antifungal activity
      of these ten compounds was evaluated using the microdilution broth method against
      42 isolates of four different Candida species. Among all tested compounds, the
      halogen substituted triazole 2-[1-(4-chlorophenyl)-1H-(1,2,3)triazol-4-yl]propan
      2-ol, revealed the best antifungal profile, showing that further modifications
      could be done in the structure to obtain a better drug candidate in the future.

PMID- 22592092
TI  - A nucleoside- and ritonavir-sparing regimen containing atazanavir plus
      raltegravir in antiretroviral treatment-naive HIV-infected patients: SPARTAN
      study results.
AB  - BACKGROUND: Nucleoside and ritonavir (RTV) toxicities have led to increased
      interest in nucleoside reverse transcriptase inhibitors (NRTIs) and RTV-sparing
      antiretroviral regimens. SPARTAN was a multicenter, randomized, open-label,
      noncomparative pilot study evaluating the efficacy, safety, and resistance
      profile of an investigational NRTI- and RTV-sparing regimen (experimental
      atazanavir [ATV] dose 300 mg bid + raltegravir [RAL] 400 mg bid [ATV+RAL]). The
      reference regimen consisted of ATV 300 mg/RTV 100 mg qd + tenofovir (TDF) 300
      mg/emtricitabine (FTC) 200 mg qd (ATV/r+TDF/FTC). METHODS: Treatment-naive HIV
      infected patients with HIV-RNA >=5,000 copies/mL were randomized 2:1 to receive
      twice-daily ATV+RAL (n=63) or once-daily ATV/r+TDF/FTC (n=31). Efficacy at 24
      weeks was determined by confirmed virologic response (CVR; HIV-RNA <50 copies/mL)
      with noncom-pleters counted as failures based on all treated subjects. RESULTS:
      The proportion of patients with CVR HIV RNA <50 copies/mL at week 24 was 74.6%
      (47/63) in the ATV+RAL arm and 63.3% (19/30) in the ATV/r+TDF/FTC arm. Systemic
      exposure to ATV in the ATV+RAL regimen was higher than historically observed with
      ATV/r+TDF/ FTC. Incidence of Grade 4 hyperbilirubinemia was higher on ATV+RAL
      (20.6%; 13/63) than on ATV/r+TDF/FTC (0%). The criteria for resistance testing
      (virologic failure [VF]: HIV-RNA >=400 copies/mL) was met in 6/63 patients on
      ATV+RAL, and 1/30 on ATV/r+TDF/FTC; 4 VFs on ATV+RAL developed RAL resistance.
      CONCLUSIONS: ATV+RAL, an experimental NRTI- and RTV-sparing regimen, achieved
      virologic suppression rates comparable to current standards of care for treatment
      naive patients. The overall profile did not appear optimal for further clinical
      development given its development of resistance to RAL and higher rates of
      hyperbilirubinemia with twice-daily ATV compared with ATV/RTV.

PMID- 22592093
TI  - Response to combined antiretroviral therapy according to gender and origin in a
      cohort of naive HIV-infected patients: GESIDA-5808 study.
AB  - BACKGROUND: We analyzed differences in response to combined antiretroviral
      therapy (cART) according to sex and geographic origin in a retrospective
      comparative study of Spanish-born and immigrant patients initiating cART.
      METHODS: The primary endpoint was time to treatment failure (TTF), defined as
      virological failure, death, opportunistic infection, interruption of cART, or
      loss to follow-up. Late diagnosis was defined as a CD4+ cell count <= 200
      cells/mm3 and/or AIDS at initiation of cART. Survival was analyzed using Kaplan
      Meier analysis and Cox regression. RESULTS: We followed 1,090 patients, of whom
      318 were women (45.6% immigrant women [IW]). At initiation of treatment, women
      had a higher CD4+ count than men (217 vs 190 cells/mm3), a lower viral load (4.7
      vs 5 log), and fewer were late starters (49% vs 59%). The adjusted risk of TTF
      between women and men was not significantly different (hazard ratio [HR], 1.10;
      95% CI, 0.79-1.53). TTF was shorter among IW than Spanish-born women (124 weeks
      [95% CI, 64-183] vs 151 [95% CI, 127-174]) and loss to follow-up was double that
      of Spanish-born women (25.5% vs 11.6%). CONCLUSIONS: Although response to cART
      was similar for both sexes, men started treatment later. IW were more frequently
      lost to follow-up and switched treatment. Measures to improve medical follow-up
      after initiation of cART should be promoted among this minority group.

PMID- 22592094
TI  - Peginterferon alfa-2a plus ribavirin for HIV-HCV genotype 1 coinfected patients:
      a randomized international trial.
AB  - BACKGROUND: The safety and efficacy of weight-based ribavirin (RBV) dosing
      regimens in patients with HIV-HCV coinfection has not been demonstrated in
      randomized clinical trials. OBJECTIVE: This randomized, double-blind,
      international, parallel-group study in specialist outpatient clinics in the
      United States, Spain, and Portugal compares the efficacy and safety of 2 RBV dose
      regimens (800 mg/day and 1000/1200 mg/day) combined with peginterferon alfa-2a
      (40KD) in patients with HIV-HCV (genotype 1) coinfection. METHODS: Patients with
      HIV-HCV coinfection, quantifiable HCV RNA in serum, HCV genotype-1 infection,
      compensated liver disease, and stable HIV disease (CD4+ count >=100 cells/uL)
      with or without ongoing antiretroviral therapy were randomized to 48 weeks'
      treatment with RBV at standard dose (800 mg/day) or weight-based dose (1000
      mg/day for patients weighing <75 kg; 1200 mg/day for patients weighing >=75 kg)
      in combination with peginterferon alfa-2a (40KD) 180 ug once a week. Planned
      enrollment was 400 patients with >=100 non-Latino African Americans. The primary
      endpoint was sustained virological response (SVR) (undetectable HCV RNA [<20
      IU/mL] at the end of a 24-week untreated follow-up period [week 72]). RESULTS:
      SVR rates were 19% (26/135) and 22% (60/275) in patients randomized to RBV 800
      mg/day and 1000/1200 mg/day, respectively (odds ratio, 1.15; 95% CI, 0.68-1.93; P
      = .6119). In the 1000/1200 mg/day RBV dose group, the incidence of hemoglobin
      reductions <100 g/L and anaemia reported as an adverse event were higher versus
      the standard 800 mg/day RBV dose group. CONCLUSIONS: Compared with the standard
      RBV dose (800 mg/day), weight-based RBV dosing (1000/1200 mg/day) did not
      significantly increase SVR rates, but did increase the incidence of anemia in HIV
      HCV (genotype 1) coinfected patients.

PMID- 22592095
TI  - Statin therapy decreases serum levels of high-sensitivity C-reactive protein and
      tumor necrosis factor-alpha in HIV-infected patients treated with ritonavir
      boosted protease inhibitors.
AB  - BACKGROUND: Statins are lipid-lowering drugs that exhibit anti-inflammatory and
      immune-modulatory properties, leading to a reduction of serum levels of C
      reactive protein (CRP) in the general population. OBJECTIVE: Because very limited
      data are available today, our objective was to assess the lipid-lowering effects
      of statins and their capacity to decrease selected soluble markers of
      inflammation in HIV-infected patients. METHODS: Retrospective cohort study of HIV
      infected adult patients with hypercholesterolemia who were receiving a stable
      antiretroviral regimen including a ritonavir-boosted protease inhibitor and who
      started a lipid-lowering therapy with rosuvastatin (10 mg daily), atorvastatin
      (10 mg daily), or pravastatin (40 mg daily) and were followed-up for at least 12
      months. One hundred and fifty-one patients were enrolled in the study: 51 in the
      rosuvastatin group, 47 in the atorvastatin group, and 53 in the pravastatin
      group. The primary observation was change in plasma lipid levels and serum
      markers of inflammation (high-sensitivity C-reactive protein [hsCRP], interleukin
      6 [IL-6], and tumor necrosis factor-alpha [TNF- alpha]), while secondary
      observations include immunovirological parameters and safety profile of statins.
      RESULTS: One year after starting the statin therapy, patients treated with
      rosuvastatin had significantly greater decreases in total cholesterol and LDL
      cholesterol than subjects on atorvastatin or pravastatin. All statins led to a
      similar, significant reduction in serum levels of hsCRP and TNF-alpha, without
      correlation between biomarkers and lipid values, and toxicity rates were similar
      for all 3 statins. CONCLUSION: Our findings suggest that rosuvastatin has a
      significantly greater lipid-lowering effect than atorvastatin or pravastatin, but
      all 3 statins exert a similar effect in lowering markers of inflammation as hsCRP
      and TNF-alpha.

PMID- 22592096
TI  - Correlation of increases in 1,25-dihydroxyvitamin D during vitamin D therapy with
      activation of CD4+ T lymphocytes in HIV-1-infected males.
AB  - BACKGROUND: In HIV-1-infected individuals, levels of CD4+ T lymphocytes are
      depleted and regulatory T-lymphocytes (Tregs) are elevated. In vitro studies have
      demonstrated effects of vitamin D on the growth and differentiation of these
      cells. We speculated whether supplementation with vitamin D could have an effect
      on CD4+ T lymphocytes or Tregs in HIV-1-infected males. METHODS: We conducted a
      placebo-controlled randomized study that ran for 16 weeks and included 61 HIV-1
      infected males, of whom 51 completed the protocol. The participants were
      randomized to 1 of 3 daily treatments: (1) 0.5-1.0 ug calcitriol and 1200 IU (30
      ug) cholecalciferol, (2) 1200 IU cholecalciferol, (3) placebo. Percentages of the
      following T-lymphocyte subsets were determined: naive CD4+ and CD8+ cells,
      activated CD4+ and CD8+ cells, and CD3+CD4+CD25+CD127low Tregs. Furthermore 1,25
      dihydroxyvitamin D, 25-hydroxyvitamin D, and parathyroid hormone were measured.
      RESULTS: No significant changes of the studied T-lymphocyte subsets occurred in
      the treatment groups compared to the placebo group. Increases in 1,25
      dihydroxyvitamin D were associated with increases in activated CD4+ T lymphocytes
      (P = .001) and Tregs (P = .01) in adjusted models. Changes in parathyroid hormone
      correlated inversely with Tregs (P = .02). Smokers had higher levels of naive
      CD4+ T lymphocytes (37% vs 25%;P = .01), naive CD8+ T lymphocytes (28% vs 19%; P
      = .03), and Tregs (9% vs 7%; P = .03). CONCLUSION: Cholecalciferol and calcitriol
      administered during 16 weeks did not change the levels of T-lymphocyte fractions
      compared to placebo. However, increases in 1,25-dihydroxyvitamin D were
      associated with an expansion of activated CD4+ cells and Tregs.

PMID- 22592097
TI  - Hepatic safety profile of fosamprenavir-containing regimens in HIV-1-infected
      patients with or without hepatitis B or C coinfection.
AB  - PURPOSE: This post hoc analysis investigated the hepatic safety profile of
      fosampre-navir (FPV) in patients monoinfected with HIV or coinfected with HIV and
      hepatitis B (HbsAg positive) and/or hepatitis C (anti-HCV antibody positive).
      METHODS: Data were pooled from 7 prospective, randomized clinical trials of FPV.
      RESULTS: Baseline demographics were generally well-matched between the 205
      coinfected (72% HCV, 24% HBV, 3% both) and 1,114 monoinfected patients in this
      analysis. At baseline, most regimens included ritonavir 100 mg (58%) or 200 mg
      (38%), and 73% of subjects were ART-naive. Over 48 weeks, the rate of treatment
      related serious adverse events was similar between the coinfected (8%; 16/205)
      and monoinfected (6%; 62/1114) groups, and the rate of treatment-related grade 2
      4 adverse events was higher in the coinfected (38%; 77/205) compared with the
      monoinfected (29%; 320/1114) group. The percentage of patients with grade 3/4
      liver enzyme elevations at any time through week 48 was 14% (ALT) and 12% (AST)
      in the coinfected group and 1% (both ALT and AST) in the monoinfected group.
      Median AST to platelet ratio index (APRI) scores decreased by 29% in both groups.
      CONCLUSION: Liver enzyme elevations in coinfected patients treated with FPV with
      or without ritonavir appear generally similar to those reported for other second
      generation protease inhibitors.

PMID- 22592098
TI  - Impact of pretreatment thrombocytosis on blood-borne metastasis and prognosis of
      gastric cancer.
AB  - BACKGROUND: Thrombocytosis has been associated with malignancies and poor
      prognostic implications in cancer patients. In the present study the prognostic
      significance of pretreatment platelet (PLT) level was assessed with regard to
      recurrence and survival in patients with primary gastric adenocarcinoma. METHODS:
      The authors reviewed the prospective data of 1593 gastric cancer patients who
      received curative gastrectomy with extended lymphadenectomy. The correlations of
      PLT level with recurrence and overall survival were evaluated by both univariate
      and multivariate analyses. RESULTS: Thrombocytosis (>= 40 * 10(4)/ MUL), present
      in 6.4% of the patients prior to curative surgery, was more frequently associated
      with advanced T and N classification, larger tumor size, anemia, and leukocytosis
      (p < 0.05). In patients with pretreatment thrombocytosis compared to those
      without it, five-year survival rate was worse (56.9% vs. 65.5%; p = 0.043), and
      recurrence rate was higher mainly due to the frequent hematogenous spread (51.0%
      vs. 34.5%; p < 0.001). Furthermore, risk of blood-borne metastasis was almost
      three-fold higher in patients with pretreatment thrombocytosis (Odds ratio 2.83
      [95% CI 1.67-4.77], p < 0.001). CONCLUSIONS: Pretreatment thrombocytosis
      correlated significantly with poor prognosis and can be used as an independent
      predictor of recurrence by blood-borne metastasis in gastric cancer.

PMID- 22592099
TI  - Sentinel node biopsy in breast cancer has a greater node positivity rate than
      axillary node sample: results from a retrospective analysis.
AB  - BACKGROUND: Sentinel node biopsy as a surgical method of axillary staging for
      early breast cancer has been widely accepted as an alternative to traditional
      four-node axillary node sampling, and is the recommended technique by the
      Association of Breast Surgery in the United Kingdom. In selected units axillary
      sampling has been compared with either radioisotope sentinel node or blue dye
      only techniques with comparable node positivity rates. There are no studies
      directly comparing combined method sentinel node biopsy (SNB) with conventional
      axillary (four) node sampling (ANS). METHODS: Data for all patients undergoing
      axillary staging by axillary node sample or sentinel node biopsy were collected,
      including those proceeding to axillary clearance as a second procedure, but
      excluding those undergoing axillary clearance as a first procedure. RESULTS: From
      January 2005 to January 2011, 641 axillary staging procedures were performed (SNB
      n=231 (36.0%), ANS n=410 (64.0%)). Baseline tumour characteristics were similar
      for the two groups except for a higher frequency of breast conservation in the
      SNB group (95.6 vs. 75.6%; p<0.0001). The proportion of cases with positive nodes
      was higher in the SNB group (20.8 vs. 14.4%; p=0.042). In patients who had
      presented with symptomatic disease, there was a significantly higher node
      positivity rate with SNB (30.9%) than with ANS (15.5%; p=0.002), despite similar
      baseline characteristics in both groups. CONCLUSION: Combined method sentinel
      node biopsy is more sensitive at detecting low volume axillary disease than
      traditional four-node sample.

PMID- 22592100
TI  - Pharmacological chaperones facilitate the post-ER transport of recombinant N370S
      mutant beta-glucocerebrosidase in plant cells: evidence that N370S is a folding
      mutant.
AB  - Gaucher disease is a prevalent lysosomal storage disease in which affected
      individuals inherit mutations in the gene (GBA1) encoding lysosomal acid beta
      glucosidase (glucocerebrosidase, GCase, EC 3.2.1.45). One of the most prevalent
      disease-causing mutations in humans is a N370S missense mutation in the GCase
      protein. As part of a larger endeavor to study the fate of mutant human proteins
      expressed in plant cells, the N370S mutant protein along with the wild-type- (WT)
      GCase, both equipped with a signal peptide, were synthesized in transgenic
      tobacco BY2 cells, which do not possess lysosomes. The enzymatic activity of
      plant-recombinant N370S GCase lines was significantly lower (by 81-95%) than that
      of the WT-GCase lines. In contrast to the WT-GCase protein, which was efficiently
      secreted from tobacco BY2 cells, and detected in large amounts in the culture
      medium, only a small proportion of the N370S GCase was secreted. Pharmacological
      chaperones such as N-(n-nonyl) deoxynojirimycin and ambroxol increased the steady
      state mutant protein levels both inside the plant cells and in the culture
      medium. These findings contradict the assertion that small molecule chaperones
      increase N370S GCase activity (as assayed in treated patient cell lysates) by
      stabilizing the enzyme in the lysosome, and suggest that the mutant protein is
      impaired in its ability to obtain its functional folded conformation, which is a
      requirement for exiting the lumen of the ER.

PMID- 22592102
TI  - Randomized controlled trial of 4 compared with 6 mo of exclusive breastfeeding in
      Iceland: differences in breast-milk intake by stable-isotope probe.
AB  - BACKGROUND: The WHO recommends exclusive breastfeeding (EBF) for 6 mo after
      birth. However, the time at which breast milk ceases to provide adequate energy
      and nutrition, requiring the introduction of complementary foods, remains
      unclear. Most studies that investigated this issue were observational and
      potentially confounded by variability in social circumstances or infant growth.
      OBJECTIVE: We hypothesized that EBF infants would consume more breast milk at age
      6 mo than infants receiving breast milk and complementary foods. DESIGN: We
      measured anthropometric outcomes, body composition, and breast-milk intake at age
      6 mo in infants who were randomly assigned at age 4 mo either to 6-mo EBF or to
      the introduction of complementary foods with continued breastfeeding. We
      recruited 119 infants from health centers in Reykjavik and neighboring
      municipalities in Iceland. In 100 infants who completed the protocol (50/group),
      breast-milk intake was measured by using stable isotopes, and complementary food
      intakes were weighed over 3 d in the complementary feeding (CF) group. RESULTS:
      Breast-milk intake was 83 g/d (95% CI: 19, 148 g/d) greater in EBF (mean +/- SD:
      901 +/- 158 g/d) than in CF (818 +/- 166 g/d) infants and was equivalent to 56
      kcal/d; CF infants obtained 63 +/- 52 kcal/d from complementary foods. Estimated
      total energy intakes were similar (EBF: 560 +/- 98 kcal/d; CF: 571 +/- 97
      kcal/d). Secondary outcomes (anthropometric outcomes, body composition) did not
      differ significantly between groups. CONCLUSIONS: On a group basis, EBF to age 6
      mo did not compromise infant growth or body composition, and energy intake at age
      6 mo was comparable to that in CF infants whose energy intake was not constrained
      by maternal breast-milk output.

PMID- 22592101
TI  - Is concordance with World Cancer Research Fund/American Institute for Cancer
      Research guidelines for cancer prevention related to subsequent risk of cancer?
      Results from the EPIC study.
AB  - BACKGROUND: In 2007 the World Cancer Research Fund (WCRF) and the American
      Institute of Cancer Research (AICR) issued 8 recommendations (plus 2 special
      recommendations) on diet, physical activity, and weight management for cancer
      prevention on the basis of the most comprehensive collection of available
      evidence. OBJECTIVE: We aimed to investigate whether concordance with the
      WCRF/AICR recommendations was related to cancer risk in the European Prospective
      Investigation into Cancer and Nutrition (EPIC) study. DESIGN: The present study
      included 386,355 EPIC participants from 9 European countries. At recruitment,
      dietary, anthropometric, and lifestyle information was collected. A score was
      constructed based on the WCRF/AICR recommendations on weight management, physical
      activity, foods and drinks that promote weight gain, plant foods, animal foods,
      alcoholic drinks, and breastfeeding for women; the score range was 0-6 for men
      and 0-7 for women. Higher scores indicated greater concordance with WCRF/AICR
      recommendations. The association between the score and cancer risk was estimated
      by using multivariable Cox regression models. RESULTS: Concordance with the score
      was significantly associated with decreased risk of cancer. A 1-point increment
      in the score was associated with a risk reduction of 5% (95% CI: 3%, 7%) for
      total cancer, 12% (95% CI: 9%, 16%) for colorectal cancer, and 16% (95% CI: 9%,
      22%) for stomach cancer. Significant associations were also observed for cancers
      of the breast, endometrium, lung, kidney, upper aerodigestive tract, liver, and
      esophagus but not for prostate, ovarian, pancreatic, and bladder cancers.
      CONCLUSION: Adherence to the WCRF/AICR recommendations for cancer prevention may
      lower the risk of developing most types of cancer.

PMID- 22592103
TI  - The menopause transition experiences of Chinese Singaporean women: an exploratory
      qualitative study.
AB  - BACKGROUND: Menopause, a developmental occurrence that takes place in midlife,
      marks the end of a woman's fertile phase. Cultural norms, social influences, and
      personal perceptions related to menopause may influence its meaning and how each
      woman experiences this transition. Little is known about the menopausal
      experiences of Asian women. PURPOSE: This study explores the menopause transition
      experiences of ethnic Chinese women in Singapore. METHODS: Using a qualitative
      design, the researchers conducted audio-taped interviews in 2010 with 14
      menopausal and postmenopausal Chinese Singaporean women aged 40-60 years.
      Thematic analysis was used to analyze interviews. RESULTS: Two main themes were
      identified: (a) experiencing symptoms and (b) managing symptoms during menopause
      transition. The most commonly reported symptoms were abnormal bleeding, hot
      flushes, and emotional changes. Most participants described their transition to
      be uneventful and ordinary and reported two significant symptoms at most. The
      strategies women used to manage their transition included using Western and
      traditional Chinese medical interventions and seeking support from family and
      friends. CONCLUSIONS: This study provides new insights into how ethnic Chinese
      women in Singapore experience menopause transition. Findings can assist nurses
      and healthcare workers in the local context to better understand menopausal
      women's needs and guide nurses to implement suitable health promotional
      strategies for women under their care in both hospital and community settings.
      IMPLICATIONS FOR PRACTICE: Although ethnicity is not necessarily a determinant of
      symptom experience during menopause transition, health education for menopausal
      women should be based on knowledge of culture-specific practices. Nurses caring
      for menopausal women in hospital and community settings in Singapore should
      evaluate the use of medications prescribed by Western and Chinese herbal medical
      professionals as well as those that are self-prescribed.

PMID- 22592104
TI  - Gender-related differences in the human rights needs of patients with mental
      illness.
AB  - BACKGROUND: Individuals with mental illness commonly experience human rights
      violations while seeking to meet their basic needs. There is lack of research in
      developing countries on gender-related differences in human rights needs.
      PURPOSE: This study investigated gender differences in perceived human rights
      needs at the family and community levels in individuals with mental illness in
      India. METHODS: This descriptive study surveyed 100 asymptomatic individuals with
      mental illness at a tertiary care center. Subject selection employed a random
      sampling method. Data were collected using face-to-face interviews based on a
      structured needs assessment questionnaire. Data were analyzed and interpreted
      using descriptive and inferential statistics. RESULTS: Subjects enjoyed a
      satisfactory level of fulfillment in the physical dimension of human rights
      needs, which included food, housing, and clothing. Men expressed lower
      satisfaction than women with perceived human rights needs fulfillment in the
      emotional dimension. This included fear of family members (chi = 9.419, p < .024)
      and being called derogatory names (chi = 8.661, p < .034). Women expressed lower
      satisfaction than men with perceived human rights needs fulfillment in social and
      ethical dimensions. The former included freedom to leave the home (chi = 11.277,
      p < .010), and the latter included sexual abuse by family members (chi = 9.491, p
      < .019). Men felt more discriminated than women due to perceptions of mental
      illness in the community domain (chi = 10.197, p < .037). CONCLUSION: This study
      suggests that family members and communities need to be educated regarding the
      human rights needs of people with mental illness and that legislation must be
      strengthened to meet the human rights needs of this disadvantaged population.

PMID- 22592105
TI  - The coping process in adults with acute leukemia undergoing hematopoietic stem
      cell transplantation.
AB  - BACKGROUND: The increasing numbers of leukemia cancer survivors treated with
      hematopoietic stem cell transplantation (HSCT) face numerous challenges after
      their transplant procedure. Little information has been published regarding the
      coping process of this population. Understanding how they cope with this life
      threatening disease can assist healthcare professionals to provide holistic care.
      PURPOSE: This study was designed to elicit the coping process of adults
      experiencing acute leukemia who underwent HSCT therapy. METHODS: This
      longitudinal qualitative study and grounded theory took place during 2009-2011.
      Ten adults with acute leukemia scheduled for HSCT were recruited from Shariati
      Hospital in Tehran, Iran. A series of pretransplant and posttransplant interviews
      were held in the hospital's HSCT units. Final interviews took place 2-6 months
      posttransplant in the hospital's outpatient clinic. RESULTS: The five categories
      that emerged from the data included perceived threat, suspension between fear and
      hope, rebirth, contextual factors, and coping strategies. Although patients
      vacillated within the coping spectrum (i.e., the "buffer zone" between fighting
      and acquiescing), "finding meaning" was identified as the final outcome of their
      experience that indicated effective coping. CONCLUSIONS/IMPLICATION FOR PRACTICE:
      Each patient perceives leukemia and HSCT therapy uniquely. This life-threatening
      disease can significantly affect patient perception and change patient lives both
      temporarily and permanently. Nurses can apply effective interventions to help
      patients cope with their unique situation, find meaning and hope, and allay fear
      and stress.

PMID- 22592106
TI  - The relationship between nutritional status and physical function, admission
      frequency, length of hospital stay, and mortality in old people living in long
      term care facilities.
AB  - BACKGROUND: Nutrition is an important issue for elderly residents of long-term
      care facilities (LTCFs). About 20% of elderly LTCF residents in Taiwan are
      malnourished. PURPOSE: This study investigated correlations between nutritional
      status and physical function, admission frequency, hospitalstay duration, and
      mortality in elderly LTCF residents. METHODS: Researchers used a retrospective
      study design and convenient sampling to enroll 174 subjects aged 67 to 105 years
      (average, 82.5 years) who were living in legally registered LTCFs in Beitou
      District, Taipei City, Taiwan. A review of LTCF resident files provided data on
      subjects' demographics, physical examination laboratory results for the most
      recent 1-year period, anthropometry, physical function, admission frequency,
      hospital stay duration, and causes of admissions. Subjects had lived in their
      LTCF for more than 1 year before their enrollment date. Subjects who died during
      and after the study period were also included in analysis. RESULTS: Results
      showed significant changes over the study year in subjects' nutritional status,
      physical function, and calf circumference. Physical function was found
      significantly correlated with calf circumference, hospitalization status was
      found correlated with nasal-gastric tube feeding status, and eating pattern was
      found correlated with calf circumference and levels of both serum albumin and
      cholesterol. Nutritional status, calf circumference, albumin level, and
      cholesterol level also correlated significantly with hospitalization status. In
      this study, the likelihood of hospitalization increased with age and nasal
      gastric tube feeding use. Hospital stay duration for subjects receiving nasal
      gastric tube feeding was longer than that for those receiving oral feeding. Also,
      weak nutritional status scores for calf circumference and hemoglobin levels were
      factors associated with increased mortality risk. CONCLUSIONS/IMPLICATIONS FOR
      PRACTICE: Findings recommend that greater attention should be paid to the
      nutritional status of elderly persons living in LTCFs to reduce hospitalization
      and death risks, cut medical expenses, and improve quality of care.

PMID- 22592107
TI  - The psychometric testing of the diabetes health promotion self-care scale.
AB  - BACKGROUND: Health-promoting behavior is an important strategy to maintain and
      enhance health of patients with Type 2 diabetes. Few instruments have been
      developed to measure health promotion self-care behavior of patients with Type 2
      diabetes. PURPOSE: Developing and psychometric testing of the Chinese version of
      the Diabetes Health Promotion Self-Care Scale (DHPSC) for patients with Type 2
      diabetes. METHODS: Four hundred and eighty-nine patients with Type 2 diabetes
      were recruited from endocrine clinics in four hospitals in Kaohsiung City in
      southern Taiwan. Exploratory and confirmatory factor analyses were used to assess
      the construct validity of the scale. Correlations between the DHPSC and the
      satisfaction subscale of Diabetes Quality of Life, Diabetes Empowerment Scale,
      and HbA1c were calculated to evaluate concurrent validity. Internal consistency
      and test-retest reliability were used to assess the reliability of the scale. The
      study was conducted in 2007 and 2008. RESULTS: A proposed second-order factor
      model with seven subscales and 26 items fit the data well. The seven subscales
      were interpersonal relationships, diet, blood glucose self-monitoring, personal
      health responsibility, exercise, adherence to the recommended regimens, and foot
      care. The DHPSC statistically significantly correlated with the satisfaction
      subscale of Diabetes Quality of Life and the Diabetes Empowerment Scale. HbA1c
      only statistically significantly correlated with the subscale of health
      responsibility. Reliability was supported by acceptable Cronbach's alpha (range,
      .78-.94) and test-retest reliability (range, .76-.95). CONCLUSIONS/IMPLICATIONS
      FOR PRACTICE: The DHPSC has satisfactory reliability and validity. Healthcare
      providers can use the DHPSC to comprehensively assess the health promotion self
      care behaviors of patients with Type 2 diabetes.

PMID- 22592108
TI  - Knowledge, attitudes, experiences, and confidence of nurses in completing advance
      directives: a systematic synthesis of three studies.
AB  - BACKGROUND: Advance directives (ADs) are one of the few means for patients to
      indicate their end-of-life (EOL) treatment option preference. An effective and
      consistent solution for increasing the AD completion rate remains elusive. A
      literature search revealed three studies completed in the United States that
      employed an identical methodology and focused on registered nurses (RNs). These
      studies examined a variety of concepts, including nurses' knowledge, attitudes,
      experience, and confidence with regard to ADs. PURPOSE: This review completed a
      systematic synthesis of reported results from three survey studies that focused,
      respectively, on oncology, critical care, and emergency RNs who were members of
      various professional nursing organizations. METHODS: Our investigation addressed
      the following research questions: What are the knowledge, attitudes, experience,
      and confidence of RNs with regard to ADs, and what is the relationship among
      these study variables? Each study used the Knowledge, Attitudes, and Experiential
      Survey on Advance Directives Instrument to obtain findings. RESULTS: Findings
      indicated that level of knowledge of nurses was about 60% correct and that nurses
      reported a moderate level of confidence related to ADs. Nurses stated they were
      experienced in AD discussions and agreed with attitude statements indicating
      support of ADs. Advocacy was a theme in the findings of these studies, as most
      nurses agreed with the statement that nurses should uphold patients' wishes. Time
      was identified as an impediment to AD completion. Critical care nurses had higher
      levels of awareness of ADs, as compared with oncology and emergency room nurses,
      although the cause of this difference is unclear. Although RNs provided AD
      education and explanations and described the various types of EOL care, these
      study subjects suggested that discussions of patients' prognoses may be an
      intervention more appropriate for nurses or other clinicians with advanced
      education and training. CONCLUSION/LIMITATIONS: The low Cronbach's alpha values
      in the attitude scales within the survey instrument posed limitations in the
      original research on the use of attitude scale scores in statistical analysis.
      The data examined in this study was obtained from published reports, which
      limited the synthesis and analysis of study findings. Nurses need to refine their
      role in AD discussions with patients. End-of-life discussions should be an
      interwoven process between RNs and the multidisciplinary team.

PMID- 22592109
TI  - Clinical nurse preceptor teaching competencies:  relationship to locus of control
      and self-directed learning.
AB  - BACKGROUND: An effective preceptor is a vital component of a strong learning
      experience for learners. Many clinical preceptors provide on-site supervision and
      clinical teaching but lack the skills necessary to be effective teachers. Few
      studies have examined the factors related to teaching competence among clinical
      nurse preceptors. PURPOSE: This article is a report of a study that examined (a)
      the differences in teaching competence by preceptor background, (b) the influence
      of locus of control on self-evaluated teaching competence, (c) the association
      between self-directed learning and self-evaluated teaching competence, and (d)
      the predictors of self-evaluated teaching competence among clinical nurse
      preceptors. METHODS: This descriptive and correlational study used a cross
      sectional survey of a convenience sample of 243 clinical nurse preceptors from a
      medical center in northern Taiwan. Of these, 242 completed questionnaires for an
      effective response rate of 99.6%. The self-evaluated Teaching Competencies Scale,
      Internal-External Scale, and Self-Directed Learning Instrument were used to
      assess teaching competencies and related factors among clinical nurse preceptors.
      Descriptive statistics, one-way ANOVA, Mann-Whitney test, and multivariate linear
      regression were used to analyze data. RESULTS: Clinical nurse preceptors averaged
      4.03 in teaching competence, indicating a moderately above average score. Higher
      teaching competence was associated with older age, being married, >10-year work
      experience, not assigned by unit manager, and good internal locus of control.
      Self-directed learning significantly correlated with teaching competence (r =
      .62). Internal locus of control and self-directed learning were significant
      independent predictors of teaching competence after adjusting for age, marital
      status, total years as a clinical nurse preceptor, and willingness to be a
      clinical nurse preceptor. Together, these accounted for 33.6% of teaching
      competence variance. CONCLUSIONS: Nurse managers should recognize all factors and
      characteristics of clinical nurse preceptors that influence teaching competence
      to help achieve optimal learning outcomes for nursing staff and students.

PMID- 22592110
TI  - Preceptor-guided clinical practica and the learning experiences of nursing
      students.
AB  - BACKGROUND: In Taiwan, nearly one third of newly graduated nurses quit their
      first nursing job within 3 months and many never return to nursing. Because
      traditional clinical practice designs do not offer adequate opportunities for
      students to work independently, many senior nursing students lack self-confidence
      in their nursing skills and are not familiar with the day-to-day realities of
      nursing even after completing all their required clinical practica. A model for a
      preceptor-guided clinical practicum was designed to address this concern.
      PURPOSE: The aim of this study was to explore the learning experiences of senior
      nursing students who worked with preceptors during their clinical practica.
      METHODS: Thirteen female nursing students were interviewed to discover their
      perceptions of their preceptor-guided clinical practicum. All interviews were
      tape recorded and transcribed. Descriptions were analyzed using Colaizzi's
      phenomenological methodology. RESULTS: Four themes emerged from the data that
      described the preceptorship experience in the clinical practicum: (1) information
      and new experience overload, (2) feelings of loneliness and stress, (3)
      questioning whether strict preceptors achieve the best results, and (4) beginning
      to feel like a nurse. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Findings suggest
      that it is important for nurse educators to be clear and precise about the
      expectations of the preceptorship experience. Orientation for both preceptors and
      students is essential. Support and encouragement throughout the entire practicum
      experience for preceptors and students is necessary to ensure program success.

PMID- 22592112
TI  - Prognosis of elderly patients subjected to mechanical ventilation in the ICU.
AB  - OBJECTIVE: To analyze the prognosis of mechanically ventilated elderly patients
      in the Intensive Care Unit (ICU). DESIGN AND SCOPE: Sub-analysis of a prospective
      multicenter observational cohort study conducted over a period of two years in 13
      medical-surgical ICUs in Spain. PATIENTS: Adult patients who required mechanical
      ventilation (MV) for longer than 24 hours. INTERVENTIONS: None. STUDY VARIABLES:
      Demographic data, APACHE II, SOFA, reason for MV, comorbidity, functional
      condition, reintubation, duration of MV, tracheotomy, ICU mortality, in-hospital
      mortality. RESULTS: A total of 1661 patients were recruited. Males accounted for
      67.9% (n=1127), with a mean age of 62.1 +/- 16.2 years. APACHE II: 20.3 +/- 7.5.
      Total SOFA: 8.4 +/- 3.5. Four hundred and twenty-three patients (25.4%) were >=
      75 years of age. Comorbidity and functional condition rates were poorer in these
      patients (p<0.001 for both variables). Mortality in the ICU was higher in the
      elderly patients (33.6%) than in the younger subjects (25.9%) (p=0.002). Also, in
      hospital mortality was higher in those >= 75 years of age. No differences in
      duration of MV, prevalence of tracheostomy or reintubation incidence were found.
      Regarding the indication for MV, only the patient >= 75 years of age with
      pneumonia, sepsis or trauma had a higher in-ICU mortality than the younger
      patients (46.3% vs 33.1%, p=0.006; 55% vs 25.8%, p=0.002; 63.6% vs 4.5%, p<0,001,
      respectively). No differences were found referred to other reasons for MV.
      CONCLUSION: Older patients (>= 75 years) have significantly higher in-ICU and in
      hospital mortality than younger patients without differences in the duration of
      mechanical ventilation. Differences in mortality were at the expense of
      pneumonia, sepsis and trauma.

PMID- 22592113
TI  - Mantle cell lymphoma-like lymphomas in c-myc-3'RR/p53+/- mice and c-myc
      3'RR/Cdk4R24C mice: differential oncogenic mechanisms but similar cellular
      origin.
AB  - Mantle cell lymphoma (MCL) is a malignant lymphoproliferative B-cell disorder
      that does not occur spontaneously in mice but experimental mice model have been
      developed. Recently two different mice models prone to develop MCL-like lymphomas
      were generated: c-myc-3'RR/Cdk4(R24C) mice and c-myc-3'RR/p53+/- mice. Comparison
      of their gene expression profiles does not highlight specific differences other
      than those in relation with their specific mutational status (i.e., Cdk4(R24C)
      mutation or p53 mutations). We propose that similarly to typical human MCL and
      its blastoid or cyclin-D1 variants that correspond to the same genetic entity,
      MCL-like lymphomas of c-myc-3'RR/ p53+/- mice and c-myc-3'RR/Cdk4(R24C) mice
      represent a spectrum of the same entity.

PMID- 22592114
TI  - A multidisciplinary approach to engage VFR migrants in Madrid, Spain.
AB  - VFRs are at a greater risk of contracting travel-related illnesses such as
      malaria, and their knowledge about travel health tends to be poor. Since 2009,
      community-based activities targeting potential and impending VFRs were performed
      by a multidisciplinary team in Madrid, Spain. The design and distribution of
      multilingual and culturally-sensitive material following a qualitative research,
      and intercultural mediators were key tools of the health education programme.

PMID- 22592115
TI  - [Consensus document on vaccination in the immunocompromised: some
      considerations].

PMID- 22592116
TI  - [Guillain- Barre syndrome: pharyngeal-cervical-brachial variant].

PMID- 22592117
TI  - [Mortality and morbidity in very low birth weight infants in the Basque Country
      and Navarra (2001-2006): population-based study].
AB  - INTRODUCTION: This study describes very low birth weight (VLBW) infant morbidity
      and mortality in Basque Country and Navarra neonatal units between the years 2001
      2006, and evaluates the factors that affect the mortality. PATIENTS AND METHODS:
      A descriptive observational study of a cohort of 1,318 VLBW infants in neonatal
      units in five Basque Country and Navarra hospitals between 2001 and 2006. A total
      of 37 variables included in EuroNeoNet database were collected as regards,
      perinatal risk and protective factors, demographic characteristics, length of
      stay, interventions, morbidity and mortality. RESULTS: A total of 94% of pregnant
      women received prenatal care and 78.7% antenatal steroids. In both cases there
      was a significant increase during the period studied. A total of 42% of
      pregnancies were multiple and in 63% delivery was by Caesarean section.
      Bronchopulmonary dysplasia statistically significantly decreased from 20% to 15%.
      The incidence of intraventricular haemorrhage grade III or IV was 7.5% and for
      periventricular leukomalacia it was 3.1%. Vertical infection was diagnosed in 4%
      of infants and sepsis or late meningitis in 25%, necrotizing enterocolitis in 9%
      and patent ductus arteriosus in 14% of the infants. The prophylactic or
      therapeutic treatment with indometacin or ibuprofen decreased significantly
      during the study. The overall rate of total, late and first day neonatal
      mortality was almost constant during this period of time. Nevertheless, the early
      neonatal mortality showed a decreasing trend and with a significant difference
      between sexes, being higher in males. CONCLUSION: This population-based study
      provides valuable information on clinical outcomes in NICUs, and may help in
      planning strategies to improve health care quality, and to reduce the morbidity
      and mortality in these neonates at high risk.

PMID- 22592118
TI  - Summing up.

PMID- 22592119
TI  - Apolipoprotein B secretory regulation by degradation.
AB  - In this short review, we discuss apolipoprotein B100 and the assembly of very low
      density lipoproteins. In particular, we address the nature and importance of co-
      and posttranslational degradation of apolipoprotein B100 during the assembly
      process. We also provide a short historical background to the development of the
      current model for the degradation of apolipoprotein B100.

PMID- 22592120
TI  - Macrophage heterogeneity: a personal scientific journey.
AB  - Although already evident from the earliest days of macrophage research, the
      diversity of macrophage distribution, morphology, and function continues to
      attract immunologists interested in their role in physiology and disease.
      Contemporary tools of cellular and molecular analysis have begun to unravel their
      versatile and adaptable gene expression, the result of differentiation and
      modulation by their environment. In this brief account, I outline the history of
      my personal involvement in this subject.

PMID- 22592122
TI  - Arthroscopic mosaicplasty for osteochondral lesions of the knee: computer
      assisted navigation versus freehand technique.
AB  - PURPOSE: The purpose of this study was to compare a freehand arthroscopic
      approach versus mosaicplasty for treatment of osteochondral lesions of the knee
      with a navigated arthroscopic technique. METHODS: Four whole cadaveric lower
      limbs were used. A conventional navigation system was used in combination with an
      autologous osteochondral graft transplantation system (Osteochondral Autograft
      Transfer System [OATS]; Arthrex, Naples, FL). The congruity of the articular
      surface was measured with the navigation probe to detect any difference between
      the surface created by the grafts and the surface of the femoral condyle
      surrounding them. The angle relates to a line perpendicular to the articular
      surface. This line is made by the cutting instrument for graft harvesting and
      insertion and the articular surface. RESULTS: The mean angle of graft harvest was
      3.4 degrees  (range, 0 degrees  to 10 degrees ) in the navigated group versus
      14.8 degrees  (range, 6 degrees  to 26 degrees ) in the freehand group (P <
      .0003). The mean angle for recipient-site coring was 1.5 degrees  (range, 0
      degrees  to 5 degrees ) in the navigated group versus 12.6 degrees  (range, 4
      degrees  to 17 degrees ) in the freehand group (P < .0003). The mean angle of
      graft placement was 2 degrees  (range, 1 degrees  to 5 degrees ) in the navigated
      group versus 10.8 degrees  (range, 5 degrees  to 15 degrees ) in the freehand
      group (P = .0002). The mean protrusion height of the plug was 0.23 mm (range, 0.1
      to 0.5 mm; SD, 0.16) in the navigated group versus 0.34 mm (range, 0.0 to 0.7 mm;
      SD, 0.25) in the freehand group (P = .336). CONCLUSIONS: Computer-assisted
      arthroscopic mosaicplasty for treatment of osteochondral lesions in the cadaveric
      model presented in this study allows permanent visualization of the angle of
      recipient-site preparation, the depth of the donor plug and the recipient plug,
      and the angle of insertion of the graft at the recipient site. CLINICAL
      RELEVANCE: This study shows evidence of potentially greater precision and
      reproducibility of navigated arthroscopic mosaicplasty when compared with an
      arthroscopic freehand technique in a cadaveric model. However, true clinical
      outcome benefit will only be elucidated upon performance of appropriate clinical
      studies.

PMID- 22592123
TI  - A biomechanical comparison of tendon-bone interface motion and cyclic loading
      between single-row, triple-loaded cuff repairs and double-row, suture-tape cuff
      repairs using biocomposite anchors.
AB  - PURPOSE: To compare tendon-bone interface motion and cyclic loading in a single
      row, triple-loaded anchor repair with a suture-tape, rip-stop, double-row rotator
      cuff repair. METHODS: Using 18 human shoulders from 9 matched cadaveric pairs, we
      created 2 groups of rotator cuff repairs. Group 1 was a double-row, rip-stop,
      suture-tape construct. Group 2 was a single-row, triple-loaded construct. Before
      mechanical testing, the supraspinatus footprint was measured with calipers. A
      superiorly positioned digital camera optically measured the tendon footprint
      motion during 60 degrees  of humeral internal and external rotation. Specimens
      were secured at a fixed angle not exceeding 45 degrees  in reference to the load.
      After preloading, each sample was cycled between 10 N and 100 N for 200 cycles at
      1 Hz, followed by destructive testing at 33 mm/s. A digital camera with tracking
      software measured the repair displacement at 100 and 200 cycles. Ultimate load
      and failure mode for each sample were recorded. RESULTS: The exposed anterior
      footprint border (6.5% +/- 6%) and posterior footprint border (0.9% +/- 1.7%) in
      group 1 were statistically less than the exposed anterior footprint border (30.3%
      +/- 17%) and posterior footprint border (29.8% +/- 14%) in group 2 (P = .003 and
      P < .001, respectively). The maximal internal rotation and external rotation
      tendon footprint displacements in group 1 (1.6 mm and 1.4 mm, respectively) were
      less than those in group 2 (both 3.6 mm) (P = .007 and P = .004, respectively).
      Mean displacement after 100 cycles for group 1 and group 2 was 2.0 mm and 3.2 mm,
      respectively, and at 200 cycles, mean displacement was 2.5 mm and 4.2 mm,
      respectively (P = .02). The mean ultimate failure load in group 1 (586 N) was
      greater than that in group 2 (393 N) (P = .02). The suture-tendon interface was
      the site of most construct failures. CONCLUSIONS: The suture-tape, rip-stop,
      double-row rotator cuff repair had greater footprint coverage, less rotational
      footprint displacement, and a greater mean ultimate failure load than the triple
      loaded, single-row repair on mechanical testing. No double-row or single-row
      constructs showed 5 mm of displacement after the first 100 cycles. The most
      common failure mode for both constructs was suture tearing through the tendon.
      CLINICAL RELEVANCE: Differences in cuff fixation influence rotational tendon
      movement and may influence postoperative healing. Stronger repair constructs
      still fail at the suture-tendon interface.

PMID- 22592125
TI  - Feasibility of an objective electrophysiological loudness scaling: a kernel-based
      novelty detection approach.
AB  - OBJECTIVE: The objective of our research is to structure a foundation for an
      electrophysiological loudness scaling measurement, in particular to estimate an
      uncomfortable loudness (UCL) level by using the hybrid wavelet-kernel novelty
      detection (HWND). METHODS AND MATERIALS: Late auditory evoked potentials (LAEPs)
      were obtained from 20 normal hearing adults. These LAEPs were stimulated by 4
      intensity levels (60 decibel (dB) sound pressure level (SPL), 70 dB SPL, 80 dB
      SPL, and 90 dB SPL). We have extracted the habituation correlates in LAEPs by
      using HWND. For this, we employed a lattice structure-based wavelet frame
      decompositions for feature extraction combined with a kernel-based novelty
      detector. RESULTS: The group results showed that the habituation correlates
      degrees, i.e., relative changes within the sweep sequences, were significantly
      different among 60 dB SPL, 70 dB SPL, 80 dB SPL, and 90 dB SPL stimulation level,
      independently from the intensity related amplitude information in the averaged
      LAEPs. At these particular intensities, 60% of the subjects show the correlation
      between the novelty measures and the stimulation levels resembles a loudness
      scaling function, in reverse. In this paper, we have found a correlation in
      between the novelty measures and loudness perception as well. We have found that
      high ranges of loudness levels such as loud, upper level and too loud show
      generally 4.88% of novelty measures and comfortable ranges of loudness levels,
      i.e., soft, comfortable but soft, comfortable loud and comfortable but loud are
      generally have 12.29% of novelty measures. Additionally, we demonstrated that our
      sweep-to-sweep basis of post processing scheme is reliable for habituation
      extraction and offers an advantage of reducing experimental time as the proposed
      scheme need less than 20% of single sweeps in comparison to the amount that are
      commonly used in arithmetical average for a meaningful result. CONCLUSIONS: We
      assessed the feasibility of habituation correlates for an objective loudness
      scaling. With respect to this first feasibility study, the presented results are
      promising when using the described signal processing and machine learning
      methodology. For the group results, the novelty measures approach is able to
      discriminate 60 dB, 70 dB, 80 dB and 90 dB stimulated sweeps. In addition, a
      correlation between the novelty measures and the subjective loudness scaling is
      observed. However, more loudness perception and frequency specific experiments
      need to be conducted to determine the UCL novelty measures threshold as well as
      clinically oriented studies are necessary to evaluate whether this approach might
      be used in the objective hearing instrument fitting procedures.

PMID- 22592127
TI  - Early-stage pathogenic sequence of jaw osteoradionecrosis in vivo.
AB  - The mechanism underlying jaw osteoradionecrosis (ORN) is not fully understood,
      particularly in the early stages. To investigate bone and vessel pathogenesis in
      the early stages of jaw ORN, we generated a mandibular ORN model in miniature
      pigs (minipigs) by applying a combination of single-dose 25-Gy irradiation (IR)
      and tooth extraction. We studied 6 ORN model minipigs and 6 control, non
      irradiated minipigs. We measured dynamic morphological changes, bone-remodeling
      associated gene expression, sphingomyelinase activity, and local blood flow. Bone
      remodeling, including bone resorption and new bone formation, was observed within
      15 days post-IR. Later, an ORN-related imbalance in bone metabolism gradually
      occurred, with loss of bone regeneration capacity, collagen collapse, and
      microvascular obliteration. Within 24 hrs post-IR, sphingomyelinase significantly
      increased in irradiated tissues. At 1 wk post-IR, local blood flow increased, but
      at 15 days post-IR, it significantly decreased to 50% below normal levels. This
      study provided details of the sequential occurrences in early-stage ORN in a
      large animal model. Our results suggested that reduced local blood flow and
      consequent hypovascularity may have caused an imbalance in bone remodeling. This
      suggested that microvessel damage may play a key role in the initiation of ORN.

PMID- 22592126
TI  - BMP activity is required for tooth development from the lamina to bud stage.
AB  - Several Bmp genes are expressed in the developing mouse tooth germ from the
      initiation to the late-differentiation stages, and play pivotal roles in multiple
      steps of tooth development. In this study, we investigated the requirement of BMP
      activity in early tooth development by transgenic overexpression of the
      extracellular BMP antagonist Noggin. We show that overexpression of Noggin in the
      dental epithelium at the tooth initiation stage arrests tooth development at the
      lamina/early-bud stage. This phenotype is coupled with a significantly reduced
      level of cell proliferation rate and a down-regulation of Cyclin-D1 expression,
      specifically in the dental epithelium. Despite unaltered expression of genes
      known to be implicated in early tooth development in the dental mesenchyme and
      dental epithelium of transgenic embryos, the expression of Pitx2, a molecular
      marker for the dental epithelium, became down-regulated, suggesting the loss of
      odontogenic fate in the transgenic dental epithelium. Our results reveal a novel
      role for BMP signaling in the progression of tooth development from the lamina
      stage to the bud stage by regulating cell proliferation and by maintaining
      odontogenic fate of the dental epithelium.

PMID- 22592128
TI  - The legacy of cariologist Douglas Bratthall, an inspired scientist.
AB  - Douglas Bratthall was an inspirational cariologist known for his playful
      curiosity, thoughtful inquisitiveness, incisive scholarship, and energetic
      leadership. He became a time, mind, and global traveler who viewed his career
      path as an exotic safari. This 'Discovery!' report identifies where his era's
      burning issues have led and how they were shaped by his contributions.

PMID- 22592129
TI  - Leptin in congenital or HIV-associated lipodystrophy and metabolic syndrome: a
      need for more mechanistic studies and large, randomized, placebo-controlled
      trials.

PMID- 22592130
TI  - Sulfated oxysterol 25HC3S as a therapeutic target of non-alcoholic fatty liver
      disease.

PMID- 22592131
TI  - The sympathetic nervous system regulates the three glycerol-3P generation
      pathways in white adipose tissue of fasted, diabetic and high-protein diet-fed
      rats.
AB  - The aim of the present study was to investigate the participation of the
      sympathetic nervous system (SNS) in the control of glycerol-3-P (G3P) generating
      pathways in white adipose tissue (WAT) of rats in three situations in which the
      plasma insulin levels are low. WAT from 48 h fasted animals, 3 day-streptozotocin
      diabetic animals and high-protein, carbohydrate-free (HP) diet-fed rats was
      surgical denervated and the G3P generation pathways were evaluated. Food
      deprivation, diabetes and the HP diet provoke a marked decrease in the rate of
      glucose uptake and glycerokinase (GyK) activity, but a significant increase in
      the glyceroneogenesis, estimated by the phosphoenolpyruvate carboxykinase (PEPCK)
      activity and the incorporation of 1-[(14)C]-pyruvate into glycerol-TAG. The
      denervation provokes a reduction (~70%) in the NE content of WAT in fasted,
      diabetic and HP diet-fed rats. The denervation induced an increase in WAT glucose
      uptake of fed, fasted, diabetic and HP diet-fed rats (40%, 60%, 3.2 fold and 35%,
      respectively). TAG-glycerol synthesis from pyruvate was reduced by denervation in
      adipocytes of fed (58%) and fasted (36%), saline-treated (58%) and diabetic
      (23%), and HP diet-fed rats (11%). In these same groups the denervation reduced
      the PEPCK mRNA expression (75%-95%) and the PEPCK activity (35%-60%). The
      denervation caused a ~35% decrease in GyK activity of control rats and a further
      ~35% reduction in the already low enzyme activity of fasted, diabetic and HP diet
      fed rats. These data suggest that the SNS plays an important role in modulating
      G3P generating pathways in WAT, in situations where insulin levels are low.

PMID- 22592132
TI  - Experimental measurements and Monte Carlo calculations for (103)Pd dosimetry of
      the 12 mm COMS eye plaque.
AB  - Monte Carlo simulations and TLD dosimetry have been performed to determine the
      dose distributions along the central axis of the 12 mm COMS eye plaques loaded
      with IRA1-(103)Pd seeds. Several simulations and measurements have been employed
      to investigate the effect of Silastic insert and air in front of the eye on
      dosimetry results along the central axis of the plaque and at some critical
      ocular structures. Measurements were performed using TLD-GR200A circular chip
      dosimeters in a PMMA eye phantom. The central axis TLD chips locations were
      arranged in one central column of eye phantom, in 3 mm intervals. The off-axis
      TLD chips locations were arranged in three off-axis columns around the central
      axis column. Version 5 of the MCNP code was also used to evaluate the dose
      distribution around the plaque. The presence of the Silastic insert results in
      dose reduction of 14% at 5 mm; also about 7% dose reduction appears at the
      interface point, due to the air presence and lack of the scattering condition.
      The overall dosimetric parameters for the COMS eye plaque loaded with new
      palladium seeds are similar to a commercial widely used seed such as
      Theragenics200. As the dose calculations under TG-43 assumptions do not consider
      the effect of the plaque backing and Silastic insert for accurate dosimetry, it's
      suggested to apply the effect of the eye plaque materials and air on dosimetry
      results along the central axis of the plaque and at some critical ocular
      structures.

PMID- 22592133
TI  - Depression and anxiety are associated with a diagnosis of hypertension 5 years
      later in a cohort of late middle-aged men and women.
AB  - The aim of this study is to examine the association between symptoms of
      depression and anxiety and hypertension status. Participants (n=455, 238 women)
      were drawn from the Dutch Famine Birth Cohort Study. In 2002-2004, they attended
      a clinic assessment during which socio-demographics, anthropometrics, resting
      systolic blood pressure (SBP) and health behaviours were measured. Symptoms of
      depression and anxiety were measured using the Hospital Anxiety and Depression
      Scale. In 2008-2009, participants completed a questionnaire, which asked whether
      they ever had a physician diagnosing them as suffering from hypertension. In
      separate regression models that initially adjusted for age and then additionally
      for sex, socio-economic status, smoking, sports participation, alcohol
      consumption, resting SBP, antidepressive and anxiolytic medication, whether or
      not participants were exposed to the Dutch famine in utero, BMI and waist:hip
      ratio, both depression and anxiety were positively associated with hypertension
      status. Those who met the criterion for possible clinical depression and anxiety
      were also more likely to be hypertensive, and these associations remained
      statistically significant in the fully adjusted regression model. In conclusion,
      symptoms of depression and anxiety were associated with a diagnosis of
      hypertension assessed 5 years later, although the mechanisms underlying these
      associations remain to be determined.

PMID- 22592134
TI  - The effect of obesity on early failure after operative syndesmosis injuries.
AB  - OBJECTIVE: The goal of this investigation was to determine if obese patients with
      syndesmotic injuries have a higher incidence of early postoperative failure
      compared with nonobese patients. DESIGN: Retrospective cohort study. SETTING:
      Level 1 urban trauma center. PATIENTS AND METHODS: Two hundred thirteen patients
      with operative syndesmotic injuries were divided into 2 cohorts: obese and
      nonobese. All syndesmotic injuries were confirmed by intraoperative stress
      testing, reduced, and stabilized with internal fixation. INTERVENTION: Fixation
      of displaced syndesmosis injuries with solid 3.5- and 4.5-mm screws. MAIN OUTCOME
      MEASURES: The primary outcome was early failure of fixation, defined as revision
      surgery within 3 months for ankle mortise and/or syndesmosis displacement.
      RESULTS: Two hundred thirteen patients were identified with operative syndesmosis
      injuries, of which 102 (48%) were obese and 111 (52%) were nonobese. Fifteen
      percent (n = 15) of patients in the obese cohort sustained a failure of fixation
      compared with 1.8% (n = 2) of patients in the nonobese cohort (P = 0.0005).
      Diabetes mellitus, smoking status, and the type of construct used (eg, screw
      caliber, number of screws, and number of cortices) were not predictive of loss of
      reduction. Adjusting for injury severity, obese patients were 12 times more
      likely to suffer a loss of reduction compared with nonobese patients (odds ratio
      = 12.0, P = 0.02). CONCLUSIONS: There is a strong association between obesity and
      loss of reduction after operative treatment of the syndesmosis. Further research
      is warranted to determine if a stronger mechanical construct or more conservative
      postoperative protocol can reduce the risk of loss of reduction in obese patients
      who sustain a syndesmotic injury.

PMID- 22592136
TI  - A right atrial mass in a patient with metastatic melanoma and prostate cancer.

PMID- 22592137
TI  - Transesophageal echocardiographic monitoring during vascular surgery in a patient
      with unanticipated critical aortic stenosis.

PMID- 22592135
TI  - The application and mechanism of action of ribavirin in therapy of hepatitis C.
AB  - Ribavirin has been used as an antiviral agent for several decades. Although it
      has activity against numerous viruses, its major use clinically has been in the
      treatment of respiratory syncytial virus in paediatric patients and chronic HCV
      infection in both children and adults. This review highlights the clinical
      application and mechanism of action of ribavirin and discusses the future role of
      ribavirin in treatment of HCV where there are intense research efforts to improve
      therapy.

PMID- 22592138
TI  - Airway management and lung isolation in a patient with a massive cavernous
      hemangioma of the tongue.

PMID- 22592139
TI  - Comparison of the effects of sevoflurane, isoflurane, and desflurane on
      microcirculation in coronary artery bypass graft surgery.
AB  - OBJECTIVE: This investigation was performed to compare the effects of inhalation
      agents on microcirculation in coronary artery bypass grafting (CABG) using
      orthogonal polarization spectral imaging. DESIGN: This prospective and randomized
      study was performed in patients scheduled for CABG surgery from March through
      September 2010. SETTING: Tertiary care university hospital. PARTICIPANTS: Thirty
      patients undergoing elective CABG. INTERVENTIONS: Patients were assigned to
      sevoflurane, desflurane, or isoflurane. MEASUREMENTS AND MAIN RESULTS: Orthogonal
      polarization spectral imaging was used to evaluate the sublingual
      microcirculation. Hemodynamic variables (heart rate, mean arterial pressure,
      central venous pressure, cardiac output, and pulmonary capillary wedge pressure),
      laboratory parameters (hematocrit, lactate, and potassium), and microcirculatory
      variables (total vascular density [TVD] [mm/mm(2)], microvascular flow index
      [MFI] [arbitrary units], perfused vessel density [PVD] [mm/mm(2)], and proportion
      of perfused vessels [PPV] [percentage] were obtained before induction, after
      induction, during cardiopulmonary bypass, at the end of surgery, and 24 hours
      after surgery. The greatest alterations in microcirculation parameters were found
      during cardiopulmonary bypass. In the sevoflurane group, TVD (14.7%), PVD (22%),
      PPV (5.97%, p < 0.05), and MFI (7.69%, p > 0.05) were decreased. In the
      isoflurane group, TVD (14.7%) and PVD (20.3%) were decreased, whereas PPV (1.69%)
      and MFI (17.99%) were increased (p < 0.05). In the desflurane group, there were
      no changes in TVD and PVD, but MFI (8.99%, p > 0.05) and PPV (1.48%, p < 0.05)
      were increased in the small vessels. These changes returned to their initial
      values 24 hours postoperatively. CONCLUSIONS: Sevoflurane had a negative effect
      on the microcirculation. Isoflurane decreased vascular density and increased
      flow. Desflurane produced stable effects on the microcirculation. These
      inhalation agents induced transient alterations in microvascular perfusion.

PMID- 22592140
TI  - Police custody following drink-driving: a prospective study.
AB  - BACKGROUND: Drink-driving is a crime and traffic offences are a common cause of
      detention in police custody. Legal assessment of alcohol intoxication is based on
      breath or blood testing. We hypothesize that refusal of breath alcohol testing or
      inability to perform it can correspond to singular medical characteristics of the
      detainee, possibly assaulted or injured during the arrest. Our objective was to
      determine medical characteristics of detainees held in custody for drink-driving.
      METHODS: Prospective monocentric study (April-October, 2010) of drink-drive
      arrestees. Controls were persons aged over 18 detained for other reasons than
      drink-driving. Data collected concerned persons' characteristics and reported
      assaults or observed injuries. RESULTS: 223 drivers were tested positive for
      breath alcohol level and 55 suspected drink-drivers refused or were not able to
      complete breath test. 2212 consecutively examined persons served as controls.
      Drink-drive arrestees requested medical examination more rarely (18% and 7%, vs.
      43%, P<0.0001) and drivers tested positive for breath alcohol were more
      frequently alcohol abusers (25% vs. 14%, P<0.0001) than controls. Drivers who did
      not complete breath test more often reported assaults than those tested positive
      for breath alcohol (22% vs. 8%, P=0.007). They had more frequent traumatic
      injuries than those tested positive and than controls (29% vs. 11% and 17%,
      P=0.003 and 0.02). Only 1% of drink drivers were unfit for detention after
      medical examination. CONCLUSION: Physicians need to give attentive care to
      detained drink-drivers. Special attention should be paid to drink-drivers who
      refused or were not able to complete breath alcohol measurement.

PMID- 22592141
TI  - Changing over-the-counter ephedrine and pseudoephedrine products to prescription
      only: impacts on methamphetamine clandestine laboratory seizures.
AB  - BACKGROUND: Clandestine laboratory operators commonly extract ephedrine and
      pseudoephedrine-precursor chemicals used to synthesize methamphetamine-from over
      the-counter cold/allergy/sinus products. To prevent this activity, two states,
      Oregon in 07/2006 and Mississippi in 07/2010, implemented regulations classifying
      ephedrine and pseudoephedrine as Schedule III substances, making products
      containing them available by prescription only. Using simple pre-regulation
      versus post-regulation comparisons, reports claim that the regulations have
      substantially reduced clandestine laboratory seizures (an indicator of laboratory
      prevalence) in both states, motivating efforts to implement similar regulation
      nationally. This study uses ARIMA-intervention time-series analysis to more
      rigorously evaluate the regulations' impacts on laboratory seizures. METHODS:
      Monthly counts of methamphetamine clandestine laboratory seizures were extracted
      from the Clandestine Laboratory Seizure System (2000-early 2011) for Oregon,
      Mississippi and selected nearby states (for quasi-control). FINDINGS: Seizures in
      Oregon and nearby western states largely bottomed out months before Oregon's
      regulation, and changed little thereafter. No significant impact for Oregon's
      regulation was found. Mississippi and nearby states generally had elevated
      seizures before Mississippi's regulation. Mississippi experienced a regulation
      associated drop of 28.9 seizures (50.2%) in the series level (p<0.01), while
      nearby states exhibited no comparable decline. CONCLUSIONS: Oregon's regulation
      encountered a floor effect, making any sizable impact infeasible. Mississippi,
      however, realized a substantial impact, suggesting that laboratories, if
      sufficiently extant, can be meaningfully impacted by prescription precursor
      regulation. It follows that national prescription precursor regulation would have
      little impact in western states with low indicated laboratory prevalence, but may
      be of significant use in regions facing higher indicated prevalence.

PMID- 22592142
TI  - Improving target definition for head and neck radiotherapy: a place for magnetic
      resonance imaging and 18-fluoride fluorodeoxyglucose positron emission
      tomography?
AB  - Defining the target for head and neck radiotherapy is a critical issue with the
      introduction of steep dose gradients associated with intensity-modulated
      radiotherapy. Tumour delineation inaccuracies are a major source of error in
      radiotherapy planning. The integration of 18-fluoride fluorodeoxyglucose positron
      emission tomography ((18)FDG-PET) and magnetic resonance imaging directly into
      the radiotherapy planning process has the potential to greatly improve target
      identification/selection and delineation. This raises a range of new issues
      surrounding image co-registration, delineation methodology and the use of
      functional data and treatment adaptation. This overview will discuss the
      practical aspects of integrating (18)FDG-PET and magnetic resonance imaging into
      head and neck radiotherapy planning.

PMID- 22592143
TI  - Impact on the clinical outcome of prostate cancer by the 2005 international
      society of urological pathology modified Gleason grading system.
AB  - The 2005 International Society of Urological Pathology (ISUP) Consensus
      Conference modified the Gleason grading system for prostate cancer. In the
      modified criteria, ill-defined glands with poorly formed lumina and large
      cribriform glands with smooth borders, classically described as Gleason pattern 3
      adenocarcinoma, were redefined as Gleason pattern 4. To evaluate the clinical
      outcome of patients upgraded by the ISUP criteria, the histologic slides of 1240
      consecutive radical prostatectomy specimens at a single institution were
      reviewed, and each case of adenocarcinoma was graded on the basis of the original
      and modified Gleason criteria. A total of 806 patients with prostate cancer of
      classical Gleason score 3+3=6 or 3+4=7 and modified Gleason score 6 to 8 were
      analyzed with a median overall follow-up of 12.6 years. In the study population,
      34% of patients with classical Gleason score 3+3=6 prostate cancer were upgraded
      to modified Gleason score 7 or 8 by the ISUP criteria. Compared to patients with
      modified Gleason score 3+3=6 and patients with classical Gleason score 3+4=7, the
      upgraded patients were at intermediate risk for biochemical progression (paired
      log-rank P<=0.003) and metastasis (paired log-rank P<=0.04) after radical
      prostatectomy. The hazard ratio for upgrading was 1.60 (95% confidence interval,
      1.09-2.35, P=0.02) for biochemical recurrence and 5.02 (95% confidence interval,
      1.77-14.2, P=0.003) for metastasis. These results validate the prognostic value
      of the modified Gleason grading system and suggest that the recognition of an
      intermediate-risk histological pattern may be useful in the prognosis of patients
      with prostate cancer.

PMID- 22592144
TI  - Immunohistochemical detection of the BRAF V600E-mutated protein in papillary
      thyroid carcinoma.
AB  - The V600E mutation of the B-type Raf kinase (BRAF) gene is a common event in
      papillary thyroid carcinoma (PTC) and seems to play a key role in the development
      and progression of this disease. We evaluated the expression of the mutated BRAF
      V600E protein in 144 cases of PTC using a novel mutation-specific antibody.
      Seventy-six PTCs (52.8%) showed unequivocal diffuse cytoplasmic expression of the
      mutated BRAF protein, and the T1799A point mutation was confirmed by sequencing
      analysis in selected cases. No statistical difference in V600E BRAF protein
      expression was seen between microcarcinomas and macrocarcinomas. Further, no
      significant correlation of V600E expression with clinicopathologic parameters of
      aggressiveness such as lymph node metastasis, peritumoral infiltration, or
      perithyroidal infiltration was found. BRAF V600E protein expression was
      significantly more common in tumors with tall cell or oncocytic features but was
      less common in tumors with follicular growth pattern. Diffuse sclerosing, solid
      and follicular variants did not show the mutated BRAF protein.
      Immunohistochemical detection of the mutated V600E BRAF protein in PTC may
      facilitate mutational analysis in the clinical setting. Our data show that the
      expression of the mutated BRAF V600 protein and thus the corresponding BRAF
      mutation seems not to be per se a marker of aggressiveness but is already seen in
      clinically indolent microcarcinomas. Nevertheless, the investigation of BRAF
      V600E protein expression might be of clinical interest especially in therapy
      resistant disease, as new therapeutics inhibiting the mutated protein are
      clinically available.

PMID- 22592145
TI  - Malignant gastrointestinal neuroectodermal tumor: clinicopathologic,
      immunohistochemical, ultrastructural, and molecular analysis of 16 cases with a
      reappraisal of clear cell sarcoma-like tumors of the gastrointestinal tract.
AB  - The clinical, histologic, immunophenotypic, ultrastructural, and molecular
      features of a distinctive gastrointestinal tumor are described. Sixteen patients,
      8 women and 8 men aged 17 to 77 years (mean age, 42 y; 63% less than 40 y)
      presented with abdominal pain, intestinal obstruction, and an abdominal mass.
      Mean tumor size was 5.2 cm (range, 2.4 to 15.0 cm). The tumors arose in the small
      bowel (10), stomach (4), and colon (2) and were histologically characterized by a
      sheet-like or nested population of epithelioid or oval-to-spindle cells with
      small nucleoli and scattered mitoses. Five cases showed focal clearing of the
      cytoplasm. Scattered osteoclast-type multinucleated giant cells were present in 8
      cases. The tumor cells were positive for S-100 protein, SOX10, and vimentin in
      100% of cases, for CD56 in 70%, for synaptophysin in 56%, for NB84 in 50%, for
      NSE in 45%, and for neurofilament protein in 14% of cases. All cases tested were
      negative for specific melanocytic, gastrointestinal stromal tumors, epithelial,
      and myoid markers. Ultrastructural examination of 5 cases showed features of
      primitive neuroectodermal cells with clear secretory vesicles, dense-core
      granules, occasional gap junctions, and no evidence of melanogenesis. EWSR1 gene
      rearrangement was assessed by fluorescence in situ hybridization in 14 cases.
      Twelve cases (86%) showed split EWSR1 signal consistent with a chromosomal
      translocation involving EWSR1. One case showed extra intact signals, indicating
      that the nuclei possessed either extra copies of the EWSR1 gene or chromosome 22
      polysomy. Only 1 case showed no involvement of the EWSR1 gene. Six cases
      demonstrated rearrangement of the partner fusion gene ATF1 (46%), and 3 showed
      rearrangement of CREB1 (23%); 2 cases lacked rearrangement of either partner
      gene. Clinical follow-up was available in 12 patients and ranged from 1.5 to 106
      months. Six patients died of their tumors (mean survival, 32 mo; 83% less than 24
      mo). At last follow-up, 4 patients were alive with regional, lymph node, and
      liver metastases, and 2 patients were alive with no evidence of disease. The
      tumor described here is an aggressive form of neuroectodermal tumor that should
      be separated from other primitive epithelioid and spindle cell tumors of the
      gastrointestinal tract. The distinctive ultrastructural features and absence of
      melanocytic differentiation serve to separate them from soft tissue clear cell
      sarcomas involving the gastrointestinal tract. The designation "malignant
      gastrointestinal neuroectodermal tumor" is proposed for this tumor type.

PMID- 22592146
TI  - [Stereotactic and diagnostic imaging in radiosurgery].
AB  - Constant progress in medical imaging and particularly magnetic resonance imaging
      has profound impact in planning for stereotactic radiosurgery and radiotherapy.
      The purpose of this paper is to discuss the integration of medical imaging
      modalities in the planning process. Principles of generic algorithms to calculate
      stereotactic coordinates are treated for tomographic imaging and digital
      substraction angiography, and their accuracies are analyzed in a review of the
      literature. The algorithmic foundations and performance of automatic
      intermodality co-registration methods are developed. Finally, the MRI sequences
      useful in planning and follow-up are discussed and the role of MR angiographic
      sequences compared to conventional X-ray angiography in the particular case of
      the arteriovenous malformation planning.

PMID- 22592147
TI  - [Radiosurgery and radiotherapy in stereotaxic intracranial conditions].

PMID- 22592148
TI  - Selective determination of dopamine using quantum-sized gold nanoparticles
      protected with charge selective ligands.
AB  - We report here the selective determination of dopamine (DA) using quantum-sized
      gold nanoparticles coated with charge selective ligands. Glutathione protected
      gold nanoparticles (GS-Au(25)) were synthesized and immobilized into a sol-gel
      matrix via thiol linkers. The GS-Au(25) modified sol-gel electrode was found to
      show excellent electrocatalytic activity towards the oxidation of DA but no
      activity towards the oxidation of ascorbic acid. The role of electrostatic charge
      in the selective electrocatalytic activity of GS-Au(25) was verified by
      voltammetry of redox markers carrying opposite charges. The pH dependent
      sensitivity for the determination of DA further confirmed the charge screening
      effect of GS-Au(25). Mechanistic investigation revealed that the selectivity is
      attained by the selective formation of an electrostatic complex between the
      negatively charged GS-Au(25) and DA cation. The GS-Au(25) modified sol-gel
      electrode also showed excellent selectivity for DA in the presence of an
      interferent, ascorbic acid.

PMID- 22592149
TI  - Ultrasound assisted free radical polymerization of glycidyl methacrylate by a new
      disite phase-transfer catalyst system: A kinetic study.
AB  - The kinetics of multi-site phase-transfer catalyzed free radical polymerisation
      of glycidyl methacrylate (GMA) using potassium peroxy disulphate (PDS) as water
      soluble initiator and newly synthesized 1,4-dihexadecylpyrazine-1,4-diium
      dibromide as multi-site phase-transfer catalyst (MPTC) has been investigated in
      ethyl acetate/water two phase system at constant temperature 65+/-1 degrees C
      under nitrogen atmosphere and ultrasound irradiation conditions. The rate of
      polymerization increases with an increase in concentrations of GMA, PDS and MPTC.
      The order with respect to monomer, initiator and MPTC were found to be 1.0, 0.5
      and 1.0, respectively. The comparative study reveals that the Rp of GMA
      determined in the presence of PTC combined with ultrasound has shown more
      enhancements in the activity than PTC alone. Based on the observed results a
      suitable mechanism has been proposed to account for the experimental observations
      and its significance was discussed.

PMID- 22592150
TI  - Isothermal nucleic acid amplification technologies for point-of-care diagnostics:
      a critical review.
AB  - Nucleic Acid Testing (NAT) promises rapid, sensitive and specific diagnosis of
      infectious, inherited and genetic disease. The next generation of diagnostic
      devices will interrogate the genetic determinants of such conditions at the point
      of-care, affording clinicians prompt reliable diagnosis from which to guide more
      effective treatment. The complex biochemical nature of clinical samples, the low
      abundance of nucleic acid targets in the majority of clinical samples and
      existing biosensor technology indicate that some form of nucleic acid
      amplification will be required to obtain clinically relevant sensitivities from
      the small samples used in point-of-care testing (POCT). This publication provides
      an overview and thorough review of existing technologies for nucleic acid
      amplification. The different methods are compared and their suitability for POCT
      adaptation are discussed. Current commercial products employing isothermal
      amplification strategies are also investigated. In conclusion we identify the
      factors impeding the integration of the methods discussed in fully automated,
      sample-to-answer POCT devices.

PMID- 22592151
TI  - Size matters: how accurate is clinical estimation of traumatic wound size?
AB  - AIMS: The presentation of traumatic wounds is commonplace in the accident &
      emergency department. Often, these wounds need referral to specialist care, e.g.
      trauma & orthopaedic, plastic or maxillofacial surgeons. Documentation and
      communication of the size of the wound can influence management, e.g. Gustilo &
      Anderson classification of open fractures. Several papers acknowledge the
      variability in measurement of chronic wounds, but there is no data regarding
      accuracy of traumatic wound assessment. The authors hypothesised that the
      estimation of wound size and subsequent communication or documentation was often
      inaccurate, with high inter-observer variability. A study was designed to assess
      this hypothesis. METHODS: A total of 7 scaled images of wounds related to trauma
      were obtained from an Internet search engine. The questionnaire asked 3 questions
      regarding mechanism of injury, relevant anatomy and proposed treatment, to
      simulate real patient assessment. One further question addressed the estimation
      of wound size. 50 doctors of varying experience across several specialities were
      surveyed. The images were analysed after data collection had finished to provide
      appropriate measurements, and compared to the questionnaire results by a
      researcher blinded to the demographics of the individual. RESULTS: Our results
      show that there is a high inter-observer variability and inaccuracy in the
      estimation of wound size. This inaccuracy was directional and affected by gender.
      Male doctors were more likely to overestimate the size of wounds, whilst their
      female colleagues were more likely to underestimate size. CONCLUSIONS: The
      estimation of wound size is a common requirement of clinical practice, and
      inaccurate interpretation of size may influence surgical management. Assessment
      using estimation was inaccurate, with high inter-observer variability. Assessment
      of traumatic wounds that require surgical management should be accurately
      measured, possibly using photography and ruler measurement.

PMID- 22592152
TI  - Multi-disciplinary update on pelvic fracture associated bladder and urethral
      injuries.
AB  - Pelvic ring fractures often result in severely injured patients with multiple
      organ injuries. The most common associated injuries are intraabdominal or
      urogenital, and urogenital injuries are the most common associated injuries in
      those with severe pelvic fractures. Prompt and effective diagnosis and management
      of these injuries is essential to successful outcomes, but this is potentially
      complicated by poor communication and coordination among the many specialists
      involved. To address this, we present a multi-disciplinary review of pelvic
      fracture-associated bladder and urethral injuries that is specifically geared
      towards orthopaedic, urology, and trauma surgeons caring for these patients.

PMID- 22592153
TI  - Dermatology life quality index (DLQI): a paradigm shift to patient-centered
      outcomes.

PMID- 22592154
TI  - Conditional immortalization establishes a repertoire of mouse melanocyte
      progenitors with distinct melanogenic differentiation potential.

PMID- 22592156
TI  - A missense mutation within the helix initiation motif of the keratin K71 gene
      underlies autosomal dominant woolly hair/hypotrichosis.
AB  - Woolly hair (WH) is an abnormal variant of tightly curled hair, which is
      frequently associated with hypotrichosis. Non-syndromic forms of WH can show
      either autosomal-dominant WH (ADWH) or autosomal-recessive WH (ARWH) inheritance
      patterns. ARWH has recently been shown to be caused by mutations in either the
      lysophosphatidic acid receptor 6 (LPAR6) or lipase H (LIPH) gene. More recently,
      a mutation in the keratin K74 (KRT74) gene has been reported to underlie ADWH.
      Importantly, all of these genes are abundantly expressed in the inner root sheath
      (IRS) of human hair follicles. Besides these findings, the molecular mechanisms
      underlying hereditary WH have not been fully disclosed. In this study, we
      identified a Japanese family with ADWH and associated hypotrichosis. After
      exclusion of known causative genes, we discovered the heterozygous mutation
      c.422T>G (p.Phe141Cys) within the helix initiation motif of the IRS-specific
      keratin K71 (KRT71) gene in affected family members. We demonstrated that the
      mutant K71 protein led to disruption of keratin intermediate filament formation
      in cultured cells. To our knowledge, it is previously unreported that the KRT71
      mutation is associated with a hereditary hair disorder in humans. Our findings
      further underscore the crucial role of the IRS-specific keratins in hair follicle
      development and hair growth in humans.

PMID- 22592157
TI  - Why statistics matter: limited inter-rater agreement prevents using the psoriasis
      area and severity index as a unique determinant of therapeutic decision in
      psoriasis.
AB  - Although the demand for evidence-based decisions is increasing in clinical
      practice, recent systematic reviews on the accuracy of existing psoriasis
      severity scales, including the Psoriasis Area and Severity Index (PASI), suggest
      that their validity is not fully characterized. We simulated the evaluation of
      PASI by two practitioners in 1,000 sets of 100 patients. PASI data from several
      practitioners who examined the same patients were used to generate PASI scores by
      two practitioners, in order to compare how well commonly used statistics assess
      the inter-rater agreement for the PASI. Because the PASI score has an asymmetric
      distribution, statistics such as Pearson's linear correlation coefficient "r" and
      Spearman's rank correlation coefficient overestimated the inter-rater agreement
      of PASI as compared with the intra-class correlation coefficient (ICC; r=0.8,
      rho=0.7, ICC=0.5). When restricting the analysis to patients with a PASI <20,
      inter-rater agreement severely decreased (r=0.38, rho=0.41, ICC=0.17), resulting
      in unacceptable therapeutic decision agreement (kappa=0.38). Our study indicates
      that owing to the skewed distribution of the PASI its validity to influence
      therapeutic decisions is questionable. The ICC is preferable to the commonly used
      statistics (r and rho) for assessing the inter-rater agreement reliability of
      asymmetrically distributed scores such as the PASI.

PMID- 22592158
TI  - Porokeratotic eccrine nevus may be caused by somatic connexin26 mutations.
AB  - Porokeratotic eccrine ostial and dermal duct nevus, or porokeratotic eccrine
      nevus (PEN), is a hyperkeratotic epidermal nevus. Several cases of widespread
      involvement have been reported, including one in association with the keratitis
      ichthyosis-deafness (KID) syndrome (OMIM #148210), a rare disorder caused by
      mutations in the GJB2 gene coding for the gap junction protein connexin26 (Cx26).
      The molecular cause is, as yet, unknown. We have noted that PEN histopathology is
      shared by KID. The clinical appearance of PEN can resemble that of KID syndrome.
      Furthermore, a recent report of cutaneous mosaicism for a GJB2 mutation
      associated with KID describes linear hyperkeratotic skin lesions that might be
      consistent with PEN. From this, we hypothesized that PEN might be caused by Cx26
      mutations associated with KID or similar gap junction disorders. Thus, we
      analyzed the GJB2 gene in skin samples from two patients referred with
      generalized PEN. In both, we found GJB2 mutations in the PEN lesions but not in
      unaffected skin or peripheral blood. One mutation was already known to cause the
      KID syndrome, and the other had not been previously associated with skin
      symptoms. We provide extensive functional data to support its pathogenicity. We
      conclude that PEN may be caused by mosaic GJB2 mutations.

PMID- 22592159
TI  - Heparin-binding EGF-like growth factor promotes epithelial-mesenchymal transition
      in human keratinocytes.
AB  - We have shown that autocrine proliferation of human keratinocytes (KCs) is
      strongly dependent upon amphiregulin (AREG), whereas blockade of heparin-binding
      EGF-like growth factor (HB-EGF) inhibits KC migration in scratch wound assays.
      Here we demonstrate that expression of soluble HB-EGF (sHB-EGF) or full-length
      transmembrane HB-EGF (proHB-EGF), but not proAREG, results in profound increases
      in KC migration and invasiveness in monolayer culture. Coincident with these
      changes, HB-EGF significantly decreases mRNA expression of several epithelial
      markers including keratins 1, 5, 10, and 14 while increasing expression of
      markers of cellular motility including SNAI1, ZEB1, COX-2, and MMP1.
      Immunostaining revealed HB-EGF-induced expression of the mesenchymal protein
      vimentin and decreased expression of E-cadherin, as well as nuclear translocation
      of beta-catenin. Suggestive of a trade-off between KC motility and proliferation,
      overexpression of HB-EGF also reduced KC growth by >90%. We also show that HB-EGF
      is strongly induced in regenerating epidermis after partial-thickness wounding of
      human skin. Taken together, our data suggest that expression of HB-EGF in human
      KCs triggers a migratory and invasive phenotype with many features of epithelial
      mesenchymal transition (EMT), which may be beneficial in the context of cutaneous
      wound healing.

PMID- 22592160
TI  - T-Cadherin is an auxiliary negative regulator of EGFR pathway activity in
      cutaneous squamous cell carcinoma: impact on cell motility.
AB  - Genetic and epigenetic studies in different cancers, including cutaneous
      carcinomas, have implicated T-cadherin (T-cad) as a tumor suppressor.
      Immunohistochemical and in vitro studies have suggested that T-cad loss promotes
      incipient invasiveness in cutaneous squamous cell carcinoma (SCC). Molecular
      mechanisms are unknown. This study found that the main consequence of T-cad
      silencing in SCC is facilitation of ligand-dependent EGFR activation, whereas T
      cad overexpression impedes EGFR activation. Gain- and loss-of-function studies in
      A431 SCC cells demonstrate T-cad-controlled responsiveness to EGF with respect to
      pharmacological inhibition of EGFR and to diverse signaling and functional events
      of the EGFR activation cascade (EGFR phosphorylation, internalization, nuclear
      translocation, cell retraction/de-adhesion, motility, invasion, integrin beta1,
      and Rho small GTPases such as RhoA, Rac1, and Cdc42 activation). Further, T-cad
      modulates the EGFR pathway activity by influencing membrane compartmentalization
      of EGFR; T-cad upregulation promotes retention of EGFR in lipid rafts, whereas T
      cad silencing releases EGFR from this compartment, rendering EGFR more accessible
      to ligand stimulation. This study reveals a mechanism for fine-tuning of EGFR
      activity in SCC, whereby T-cad represents an auxiliary "negative" regulator of
      the EGFR pathway, which impacts invasion-associated behavioral responses of SCC
      to EGF. This action of T-cad in SCC may serve as a paradigm explaining other
      malignancies displaying concomitant T-cad loss and enhanced EGFR activity.

PMID- 22592161
TI  - Biomimetic smart nanocomposite: in vitro biological evaluation of zein
      electrospun fluorescent nanofiber encapsulated CdS quantum dots.
AB  - New hybrid quantum dot (QD)/nanofibers have potential applications in a variety
      of fields. A novel fluorescent nanocomposite nanofiber material, consisting of
      CdS and zein has been fabricated through the electrospinning process. A detailed
      optimization was carried out to fabricate continuous and uniform nanofibers
      without beads or droplets. The synthesized hybrid nanofibers were characterized
      by various state-of-the-art techniques such as scanning electron microscopy,
      transmission electron microscopy (TEM), TEM-energy dispersive spectrometry,
      atomic force microscopy and confocal fluorescence micrography. The optimization
      process was carried out to fabricate fibers ranging from 200 to 450 nm in
      diameter. The electrical conductivity of the zein-CdS hybrid nanofiber substrates
      was tested. The potential use of the electrospun CdS-encapsulated nanofibrous
      scaffold as substrates for cell/tissue culture was evaluated with two different
      cell types, i.e. mesenchymal stem cells and fibroblasts. The results showed that
      the electrospun fibrous scaffolds could support the attachment and the
      proliferation of cells. In addition, the cells cultured on the fibrous scaffolds
      exhibited normal cell shapes and integrated well with surrounding fibers. The
      obtained results confirmed the potential for the use of the electrospun QD
      encapsulated fluorescent nanofiber mats as scaffolds for tissue engineering.

PMID- 22592162
TI  - [Effects of exercise on the function and quality of life in the institutionalised
      elderly diagnosed with gonarthrosis].
AB  - INTRODUCTION: At present, aging and increased life expectancy implies a greater
      susceptibility to dependence, which then leads to the irreversible loss of
      quality of life, in many cases due to chronic diseases such as osteoarthritis
      (OA). The aim of this study was to determine the effect of a treatment based on
      aerobic exercise in institutionalised elderly people diagnosed with knee
      osteoarthritis. MATERIAL AND METHOD: An experimental, prospective, single blind
      study was conducted. The sample (n=31), was divided into two groups. The
      experimental group (n=17) was treated based on aerobic exercise for 4 weeks with
      2 sessions per week and each lasting 50minutes. We conducted a pre-test and post
      test assessment using a visual analogue scale, WOMAC questionnaire and SF-36 as
      measuring instruments. The statistical program SPSS15.0 was used for the analysis
      of the data. RESULTS: We obtained significant differences in the t-test for
      paired samples in the three dimensions of the WOMAC questionnaire, P<.001, in the
      perceived pain P<.001 and in the physical function, vitality and mental health
      dimensions of the SF-36 with a 95% confidence interval. CONCLUSION: Exercise gave
      positive results in functional (pain, stiffness, physical function) and
      psychological aspects (mental health and vitality) in the institutionalised
      elderly.

PMID- 22592163
TI  - Investigation of sanguinarine and chelerythrine effects on LPS-induced
      inflammatory gene expression in THP-1 cell line.
AB  - Quaternary benzo[c]phenanthridine alkaloids sanguinarine and chelerythrine have
      been used in folk medicine for their wide range of useful properties. One of
      their major effect is also anti-inflammatory activity, that is not clarified in
      detail. This study focused on the ability of these alkaloids to modulate the gene
      expression of pro-inflammatory tumour necrosis factor alpha (TNF-alpha), monocyte
      chemoattractant protein 1 (MCP-1, also known as CCL-2), interleukin (IL)-6, IL
      1beta and anti-inflammatory cytokines IL-1 receptor antagonist (IL-1RA) and IL
      10. The effect of these alkaloids was compared with that of conventional drug
      prednisone. Human monocyte-derived macrophages were pre-treated with alkaloids or
      prednisone and inflammatory reaction was induced by lipopolysaccharide. Changes
      of gene expression at the transcriptional level of mentioned cytokines were
      measured. In our study mainly affected pro-inflammatory cytokines were CCL-2 and
      IL-6. Two hours after LPS stimulation, cells influenced by sanguinarine and
      chelerythrine significantly declined the CCL-2 expression by a factors of 3.5
      (p<0.001) and 1.9 (p<0.01); for those treated with prednisone the factor was 5.3
      (p<0.001). Eight hours after LPS induction, both alkaloids significantly
      diminished the CCL-2 expression. The lower expression was found for sanguinarine-
      lower by a factor of 4.3 than for cells treated with the vehicle (p<0.001). Two
      hours after LPS stimulation, cells treated with sanguinarine decreased the IL-6
      mRNA level by a factor of 3.9 (p<0.001) compared with cells treated with the
      vehicle. Chelerythrine decreased the level of IL-6 mRNA by a factor of 1.6
      (p<0.001). Sanguinarine decreased gene expression of CCL-2 and IL-6 more than
      chelerythrine and its effect was quite similar to prednisone. Four hours after
      LPS stimulation, cells pre-treated with sanguinarine exhibited significantly
      higher expression (a factor of 1.7, p<0.001) of IL-1RA than cells without
      sanguinarine treatment. Our results help to clarify possible mechanisms of action
      of these alkaloids in the course of inflammation.

PMID- 22592164
TI  - Recent advances in the development of GTR/GBR membranes for periodontal
      regeneration--a materials perspective.
AB  - Periodontitis is a major chronic inflammatory disorder that can lead to the
      destruction of the periodontal tissues and, ultimately, tooth loss. To date, flap
      debridement and/or flap curettage and periodontal regenerative therapy with
      membranes and bone grafting materials have been employed with distinct levels of
      clinical success. Current resorbable and non-resorbable membranes act as a
      physical barrier to avoid connective and epithelial tissue down-growth into the
      defect, favoring the regeneration of periodontal tissues. These conventional
      membranes possess many structural, mechanical, and bio-functional limitations and
      the "ideal" membrane for use in periodontal regenerative therapy has yet to be
      developed. Based on a graded-biomaterials approach, we have hypothesized that the
      next-generation of guided tissue and guided bone regeneration (GTR/GBR) membranes
      for periodontal tissue engineering will be a biologically active, spatially
      designed and functionally graded nanofibrous biomaterial that closely mimics the
      native extra-cellular matrix (ECM). OBJECTIVE: This review is presented in three
      major parts, including (1) a brief overview of the periodontium and its
      pathological conditions, (2) currently employed therapeutics used to regenerate
      the distinct periodontal tissues, and (3) a review of commercially available
      GTR/GBR membranes as well as the recent advances on the processing and
      characterization of GTR/GBR membranes from a materials perspective. SIGNIFICANCE:
      Studies of spatially designed and functionally graded membranes (FGM) and in
      vitro antibacterial/cell-related research are addressed. Finally, as a future
      outlook, the use of hydrogels in combination with scaffold materials is
      highlighted as a promising approach for periodontal tissue engineering.

PMID- 22592166
TI  - Time-motion analysis of youth Olympic Taekwondo combats.
AB  - This study aimed to analyze the time-motion structure of combat phases (fighting:
      F, nonfighting: NF, and stoppage time: ST) during semifinal and final matches
      (three 1.5-minute rounds, with 1-minute rest in between) of the 2010 Italian
      Taekwondo Cadet (age 13-14 years) Championship (adolescent boys, n = 40;
      adolescent girls, n = 28) in relation to gender (adolescent boys and girls) and
      grouped weight division (light, middle, and heavy) of athletes. Regardless of
      gender, grouped weight division, round, and tournament stage, differences (p <
      0.001, effect size range: 1.92-3.02) emerged for frequency of occurrence of
      combat phases (F: 42.4 +/- 0.5%; NF: 44.5 +/- 0.7%; ST: 13.1 +/- 0.9%) and their
      mean duration (F: 2.8 +/- 1.0 seconds; NF: 6.5 +/- 1.8 seconds; ST: 13.7 +/- 5.0
      seconds). A 1:2 F to NF ratio was found, whereas a 1:3 ratio emerged when F was
      considered in relation to the sum of NF and ST. During F phase, 5 +/- 1 tactical
      movements and 4 +/- 1 technical exchanges were performed, lasting 0.6 +/- 0.1
      seconds and 0.7 +/- 0.1 seconds, respectively. These findings mirrored the
      intermittent nature of youth combat, characterized by a high occurrence of
      tactical movements and technical exchanges during F phase. The lack of
      differences for round and tournament stages indicates a limited tactical
      capability of young athletes in adopting specific match strategies, independently
      from gender and weight divisions of the athletes. To prepare young athletes to
      handle the technical-tactical demands of the match, coaches could include 7-9
      circuit stations of specific taekwondo sequences of attack and counter attack
      techniques.

PMID- 22592165
TI  - Effect of quaternary ammonium and silver nanoparticle-containing adhesives on
      dentin bond strength and dental plaque microcosm biofilms.
AB  - OBJECTIVE: Antibacterial bonding agents are promising to hinder the residual and
      invading bacteria at the tooth-restoration interfaces. The objectives of this
      study were to develop an antibacterial bonding agent by incorporation of
      quaternary ammonium dimethacrylate (QADM) and nanoparticles of silver (NAg), and
      to investigate the effect of QADM-NAg adhesive and primer on dentin bond strength
      and plaque microcosm biofilm response for the first time. METHODS: Scotchbond
      Multi-Purpose adhesive and primer were used as control. Experimental adhesive and
      primer were made by adding QADM and NAg into control adhesive and primer. Human
      dentin shear bond strengths were measured (n = 10). A dental plaque microcosm
      biofilm model with human saliva as inoculum was used to investigate biofilm
      metabolic activity, colony-forming unit (CFU) counts, lactic acid production, and
      live/dead staining assay (n = 6). RESULTS: Adding QADM and NAg into adhesive and
      primer did not compromise the dentin shear bond strength which ranged from 30 to
      35MPa (p>0.1). Scanning electron microscopy (SEM) examinations revealed numerous
      resin tags, which were similar for the control and the QADM and NAg groups.
      Adding QADM or NAg markedly reduced the biofilm viability, compared to adhesive
      control. QADM and NAg together in the adhesive had a much stronger antibacterial
      effect than using each agent alone (p<0.05). Adding QADM and NAg in both adhesive
      and primer had the strongest antibacterial activity, reducing metabolic activity,
      CFU, and lactic acid by an order of magnitude, compared to control. SIGNIFICANCE:
      Without compromising dentin bond strength and resin tag formation, the QADM and
      NAg containing adhesive and primer achieved strong antibacterial effects against
      microcosm biofilms for the first time. QADM-NAg adhesive and primer are promising
      to combat residual bacteria in tooth cavity and invading bacteria at the margins,
      thereby to inhibit secondary caries. QADM and NAg incorporation may have a wide
      applicability to other dental bonding systems.

PMID- 22592167
TI  - Thomas L. DeLorme and the science of progressive resistance exercise.
AB  - In the latter years of the Second World War, the number of American servicemen
      who had sustained orthopedic injuries was overwhelming the nation's military
      hospitals. The backlog of patients was partly because of the sheer number of
      soldiers involved in the war effort, but it was exacerbated by rehabilitation
      protocols that required lengthy recovery times. In 1945, an army physician, Dr.
      Thomas L. DeLorme experimented with a new rehabilitation technique. DeLorme had
      used strength training to recover from a childhood illness and reasoned that such
      heavy training would prove beneficial for the injured servicemen. DeLorme's new
      protocol consisted of multiple sets of resistance exercises in which patients
      lifted their 10-repetition maximum. DeLorme refined the system by 1948 to include
      3 progressively heavier sets of 10 repetitions, and he referred to the program as
      "Progressive Resistance Exercise." The high-intensity program was markedly more
      successful than older protocols and was quickly adopted as the standard in both
      military and civilian physical therapy programs. In 1951, DeLorme published the
      text Progressive Resistance Exercise: Technic and Medical Application, which was
      widely read by other physicians and medical professionals. The book, and
      DeLorme's academic publications on progressive resistance exercise, helped
      legitimize strength training and played a key role in laying the foundation for
      the science of resistance exercise.

PMID- 22592168
TI  - Physiological responses to an intensified period of rugby league competition.
AB  - This study investigated the physiological responses to an intensified period of
      rugby league competition and the subsequent impact on match performance. The
      participants were 7 rugby league players competing in an international student
      tournament. The tournament involved three 80-minute games over a 5-day period,
      with 48 hours between each match. Baseline measures of upper and lower body
      neuromuscular functions via a plyometric press-up (PP) and countermovement jump
      (CMJ), respectively (peak power and peak force were measured), blood creatine
      kinase (CK), and perceptions of well-being were assessed with a questionnaire.
      These measures were repeated every morning of the competition; neuromuscular
      fatigue and CK were additionally assessed within 2 hours after the cessation of
      each game. During each match, player movements were recorded via global
      positioning system units. There were meaningful reductions in upper (effect size
      [ES] = -0.55) and lower body (ES = -0.73) neuromuscular functions, and perceptual
      well-being (ES = -1.56) and increases in blood CK (ES = 2.32) after game 1. These
      changes increased in magnitude as the competition progressed. There were large
      reductions in the relative distance covered in high-speed running (ES = -1.49)
      and maximal accelerations (ES = -0.85) during game 3. Additionally, moderate
      reductions in the percentage of successful tackles completed were observed during
      game 3 (ES = -0.59). Collectively, these results demonstrate that during an
      intensified period of rugby league competition, characterized by only 48 hours
      between matches, fatigue will accumulate. This cumulative fatigue may compromise
      high-intensity match activities such as high-speed running, accelerations, and
      tackling. Furthermore, CMJs and PPs appear to be sensitive measures for
      monitoring neuromuscular function in rugby league players.

PMID- 22592169
TI  - Can maximal and rapid isometric torque characteristics predict playing level in
      division I American collegiate football players?
AB  - The purpose of this study was to determine if maximal and rapid isometric torque
      characteristics could discriminate starters from nonstarters in elite Division I
      American collegiate football players. Sixteen starters (mean +/- SD: age = 20.81
      +/- 1.28 years; height = 184.53 +/- 6.58 cm; and mass = 108.69 +/- 22.16 kg) and
      15 nonstarters (20.40 +/- 1.68 years; 182.27 +/- 10.52 cm; and 104.60 +/- 22.44
      kg) performed isometric maximal voluntary contractions (MVCs) of the leg flexor
      and extensor muscle groups. Peak torque (PT), rate of torque development (RTD),
      the time to peak RTD (TTRTDpeak), contractile impulse (IMPULSE), and absolute
      torque values (TORQUE) at specific time intervals were calculated from a torque
      time curve. The results indicated significant and nonsignificant differences
      between starters and nonstarters for the early rapid leg flexion torque
      characteristics that included RTD, IMPULSE, and TORQUE at 30 and 50 milliseconds,
      and TTRTDpeak. These variables also demonstrated the largest effect sizes of all
      the variables examined (0.71-0.82). None of the leg extensor variables, leg
      flexion PT, or later leg flexion rapid torque variables (>= 100 milliseconds)
      were significant discriminators of playing level. These findings suggest that the
      early rapid leg flexion torque variables may provide an effective and sensitive
      muscle performance measurement in the identification of collegiate football
      talent. Further, coaches and practitioners may use these findings when designing
      training programs for collegiate football players with the intent to maximize
      rapid leg flexion characteristics.

PMID- 22592170
TI  - Stimulus tempos and the reliability of the successive choice reaction test.
AB  - In ball game sports, players demand agility, which is a quick and adequate
      reaction to various changing stimuli. We developed a "successive choice reaction
      test" that evaluates such agility. This test requires subjects to be exposed to
      successive stimuli. Hence, it is very important to select appropriate stimulus
      tempos. In addition, it is necessary to examine the reliability of a new test.
      This study examined adequate stimulus tempos and test reliability. Fifteen
      healthy university students participated in this study. All the subjects
      conducted a successive choice reaction test with 3 kinds of tempos (1.3, 1.5, and
      2.0 seconds). To examine its reliability, the test was conducted again on another
      day. It was found that any tempo has a high reliability, that their relationships
      are close, and insignificant time differences exist among the tempos. In
      conclusion, the successive choice reaction test was judged to be useful with any
      of the above tempos.

PMID- 22592172
TI  - Effect of lower-limb compression clothing on 400-m sprint performance.
AB  - This study investigated the effects of wearing a variety of lower-limb
      compression garments on 400-m sprint performance. Eleven 400-m male runners (23.7
      +/- 5.7 years, 1.78 +/- 0.08 m, and 75.3 +/- 10.0 kg) completed six, 400-m
      running tests on an outdoor, all-weather running track on separate occasions. The
      participants completed 2 runs with long-length lower-limb compression garments
      (LG; hip-to-ankle), a combination of short-length lower-limb compression garments
      (SG; hip-to-knee) with calf compression sleeves (ankle-to-knee), or without
      compression garments (CON; shorts), in a randomized, counterbalanced order.
      Overall lap time and 100-m split times, heart rate, and ratings of perceived
      exertion (RPEs) were measured during the 400-m run. Blood lactate concentration,
      visual analogue scales for perceived soreness, feeling and arousal, and scales
      for perceived comfort and tightness when wearing compression garments, were
      assessed before (preexercise, post-warm-up) and after 400-m performance (post, 4
      minutes postexercise, after a warm-down). Statistical analysis revealed no
      differences between conditions in overall 400-m performance, 100-m split times,
      or blood lactate concentration (p > 0.05), although there was a trend for an
      increased rate of blood lactate clearance when wearing compression garments. A
      significantly lower RPE (p > 0.05) was however observed during LG (13.8 +/- 0.9)
      and SG (13.4 +/- 1.1) when compared with CON (14.0 +/- 1.0). This study has
      demonstrated that lower-limb compression garments may lower the effort perception
      associated with 400-m performance, despite there being no differences in overall
      athletic performance.

PMID- 22592173
TI  - The professional experiences and work-related outcomes of male and female
      division I strength and conditioning coaches.
AB  - The purpose of this study was to investigate the professional experiences and
      work-related outcomes of male and female Division I strength and conditioning
      coaches (SCCs). Data were collected using multiple methods, first using an online
      questionnaire and second using semistructured telephone interviews. It was found
      that although SCCs generally felt supported, satisfied, and committed, several
      issues surrounding these constructs were present. Integrating the discussion of
      gender allowed for the implications of another salient social category within
      male-dominated professional field to be explored. Several implications and future
      directions are offered.

PMID- 22592175
TI  - Effects of applied training loads on the aerobic capacity of young soccer players
      during a soccer season.
AB  - The aim of this study was to examine the effects of applied training loads on the
      aerobic capacity, speed, power, and speed endurance of young soccer players
      during 1 soccer season. The participants in the study were 19 young male soccer
      players (age: 16.61 +/- 0.31 years; weight: 64.28 +/- 6.42 kg; height: 176.58 +/-
      5.98 cm). The players completed 150 training sessions and 54 games over the
      course of 1 soccer season. The training intensity was divided into 4 categories:
      (a) aerobic performance (61% of the total training duration), (b) mixed aerobic
      anaerobic performance (34%), (c) anaerobic lactate performance (3%), and (d)
      anaerobic nonlactate performance (2%). No significant changes in the V[Combining
      Dot Above]O2max were observed throughout the season. The players' power level and
      speed endurance increased significantly with the coincident decrements in their 5
      m sprint time. The applied training loads, including 1 high-intensity training
      session of small-sided games performed during a competitive season, did not
      significantly change the aerobic capacity of the young soccer players. However,
      the participants did maintain their V[Combining Dot Above]O2max at the elite
      level. The first squad players (FSPs) reached the highest level of aerobic
      fitness in the middle of the season, whereas substitute players (SPs) at the end
      of the season. Moreover, the V[Combining Dot Above]O2max in FSP was significantly
      higher (p < 0.003) than in SP in the middle of the season.

PMID- 22592176
TI  - Effects of two training protocols on the forehand drive performance in tennis.
AB  - The aim of this study was to examine the effects of 2 training modalities on the
      tennis forehand drive performance. Forty-four tennis players (mean +/- SD: age =
      26.9 +/- 7.5 years; height = 178.6 +/- 6.7 cm; mass = 72.5 +/- 8.0 kg;
      International Tennis Number = 3) were randomly assigned into 3 groups. During 6
      weeks, the first group performed handled medicine ball (HMB) throws included in
      the regular tennis practice, the second group (overweight racket-OWR) played
      tennis forehand drives with an overweighed racket during the regular tennis
      practice, and the third group (regular tennis training-RTT) practiced only tennis
      training as usual. Before and after the 6-week program, velocity and accuracy of
      tennis crosscourt forehand drives were evaluated in the 3 groups. The main
      results showed that after 6-week training, the maximal ball velocity was
      significantly increased in HMB and OWR groups in comparison with RTT (p < 0.001
      and p = 0. 001, respectively). The estimated averaged increase in ball velocity
      was greater in HMB than in OWR (11 vs. 5%, respectively; p = 0.017), but shot
      accuracy tended to be deteriorated in HMB when compared with OWR and RTT (p =
      0.043 and p = 0.027, respectively). The findings of this study highlighted the
      efficiency of both training modalities to improve tennis forehand drive
      performance but also suggested that the HMB throws may be incorporated into the
      preseason program preferably, whereas the OWR forehand drives may be included in
      the on-season program.

PMID- 22592177
TI  - Intrarater reliability of the functional movement screen.
AB  - The Functional Movement Screen (FMS) is a tool that quantifies movement patterns
      as a way to detect performance asymmetries. Although previous study has
      investigated the reliability of FMS, no current research has examined intrarater
      reliability or how clinical experience plays a role in the reliability of this
      tool. In this controlled laboratory study design, repeated measures were used to
      investigate how experience using the FMS and clinical experience as an athletic
      trainer (AT) affects the intrarater reliability of FMS testing. Before the data
      collection, 3 individuals recruited from the university community provided signed
      informed consent to serve as videotaped models performing the FMS test. The
      participants (raters) in the study, with different levels of FMS and clinical
      experience, viewed each of the 3 videotaped models and rated the video models on
      each exercise of the FMS according to the script that was presented by one of the
      study investigators. A week later, the participants watched the same videos
      again, in a different randomized order, and rated each video model on each
      exercise. After the scores from the participants were collected from both
      sessions, the intersession scores of the FMS were examined to establish
      intrarater reliability of all the participants. Additionally, the intrarater
      reliability of different groups of clinicians and students was compared to make
      inferences about the influence of clinical experience as an AT along with
      previous experience using the FMS. The ATs with at least 6 months of experience
      using the FMS (ATExp group) had the strongest intrarater reliability [intraclass
      correlation coefficients, ICC (2,1): 0.946], followed by the AT group with
      moderate reliability [ICC (2,1): 0.771]. This study indicates that intrarater
      reliability is strong and seems to strengthen when the individuals have
      experience using the FMS in addition to clinical experience.

PMID- 22592178
TI  - Bikram yoga training and physical fitness in healthy young adults.
AB  - There has been relatively little longitudinal controlled investigation of the
      effects of yoga on general physical fitness, despite the widespread participation
      in this form of exercise. The purpose of this exploratory study was to examine
      the effect of short-term Bikram yoga training on general physical fitness. Young
      healthy adults were randomized to yoga training (N = 10, 29 +/- 6 years, 24
      sessions in 8 weeks) or a control group (N = 11, 26 +/- 7 years). Each yoga
      training session consisted of 90-minute standardized supervised postures
      performed in a heated and humidified studio. Isometric deadlift strength,
      handgrip strength, lower back/hamstring and shoulder flexibility, resting heart
      rate and blood pressure, maximal oxygen consumption (treadmill), and lean and fat
      mass (dual-energy x-ray absorptiometry) were measured before and after training.
      Yoga subjects exhibited increased deadlift strength, substantially increased
      lower back/hamstring flexibility, increased shoulder flexibility, and modestly
      decreased body fat compared with control group. There were no changes in handgrip
      strength, cardiovascular measures, or maximal aerobic fitness. In summary, this
      short-term yoga training protocol produced beneficial changes in musculoskeletal
      fitness that were specific to the training stimulus.

PMID- 22592179
TI  - [Coronary artery bypass after Kawasaki disease].
AB  - Kawasaki disease (KD) is a systemic vasculitis of unknown etiology, which is the
      main cause of acquired heart disease in children in developed countries. The main
      complications result from the development of coronary aneurysms which can lead to
      ischemic heart disease. We present the case of a teenage boy with a diagnosis of
      KD at the age of seven. He was treated with gammaglobulin and aspirin and
      echocardiographic evaluation in the acute phase was apparently normal. At the age
      of eleven, he developed chest pain and exertional dyspnea. Nuclear perfusion
      scans with exercise revealed hypoperfusion of the left anterior descending (LAD)
      and right coronary (RC) artery territories. Cardiac catheterization showed
      occlusion of the proximal segments of both arteries. He underwent coronary artery
      bypass graft surgery (internal mammary artery bypass graft to the LAD artery and
      saphenous vein graft to the RC artery), with a good clinical result. This case
      report highlights the importance of early diagnosis and treatment of KD and
      regular cardiological follow-up, bearing in mind the potential late complications
      of this pediatric disease.

PMID- 22592180
TI  - A gold nanoparticles based immuno-bioprobe for detection of Vi capsular
      polysaccharide of Salmonella enterica serovar Typhi.
AB  - A rapid and sensitive gold-nanobioprobe based immunoassay format has been
      presented for the detection of capsular Vi polysaccharide of Salmonella enterica
      serovar Typhi (surface antigen) using anti-Vi antibodies. The Vi antigen was
      extracted from serovar Typhi cells, under the optimised growth conditions for its
      over-expression. Anti-Vi antibodies were produced and conjugated with gold
      nanoparticles (GNPs) of definite size (~30 nm), which served as the nano-bioprobe
      in the detection system. A sandwich immunoassay was developed using
      nitrocellulose dot blot comb (8/12 wells) membranes immobilized with anti
      Salmonella antibodies at the optimal concentration (43 ng spot(-1)). The Vi
      antigen in the clinical isolates, spiked samples and also in the standard strain
      (serovar Typhi Ty2) was detected by measuring the colour intensity of GNPs and
      correlating it with the concentration of serovar Typhi in samples. Using this
      developed immunoassay technique Vi positive serovar Typhi strains could be
      detected with a sensitivity of up to 10(2) cells mL(-1) in the clinical isolates
      as well as in the spiked samples. The developed immunoassay technique could be
      useful for the detection of typhoid fever and may be important from an
      epidemiological point of view.

PMID- 22592181
TI  - Testing the link between sympathetic efferent and sensory afferent fibers in
      neuropathic pain.
AB  - The diagnosis of sympathetically maintained pain (SMP) is typically established
      by assessment of pain relief during local anesthetic blockade of the sympathetic
      ganglia that innervate the painful body part. To determine if systemic alpha
      adrenergic blockade with phentolamine can be used to diagnose SMP, we compared
      the effects on pain of local anesthetic sympathetic ganglion blocks (LASB) and
      phentolamine blocks (PhB) in 20 patients with chronic pain and hyperalgesia that
      were suspected to be sympathetically maintained. The blocks were done inrandom
      order on separate days. Patients rated the intensity of ongoing and stimulus
      evoked pain every 5 min before, during, and after the LASB and PhB. Patients and
      the investigator assessing pain levels were blinded to the time of intravenous
      administration of phentolamine (total dose 25-35 mg). The pain relief achieved by
      LASB and PhB correlated closely (r = 0.84), and there was no significant
      difference in the maximum pain relief achieved with the two blocks (t = 0.19, P >
      0.8). Nine patients experienced a greater than 50% relief of pain and
      hyperalgesia from both LASB and PhB and were considered to have a clinically
      significant component of SMP. We conclude that alpha-adrenergic blockade with
      intravenous phentolamine is a sensitive alternative test to identify patients
      with SMP.

PMID- 22592182
TI  - Do waking salivary cortisol levels correlate with anesthesiologist's job
      involvement?
AB  - Anesthetists' work carries great responsibility and can be very stressful.
      Cognitive appraisal plays a central role in stress responses; however, little is
      known about the relationship between stress appraisal and biological markers of
      stress, particularly among anesthesiologists. Stress response may be associated
      with increased levels of systemic cortisol, which can be conveniently measured in
      saliva and used as a marker for the extent of stress. The objective of this study
      was to examine the correlation between work-related cognitive variables and
      waking salivary cortisol, a possible stress marker, in anesthesiologists. Thirty
      eight anesthesiologists were assessed for work-related thought intrusions and
      perceived "mental distance" between themselves and their work, using the
      pictorial representation of illness self-measure (PRISM), and underwent an
      implicit association test reflecting implicit job-stress associations. Salivary
      cortisol was measured twice upon awakening and an hour later, in saliva samples,
      using a kit based on chemoluminescence competition assay. Only implicit job
      stress associations were correlated with waking cortisol (r = 0.35, p < 0.05).
      Furthermore, high implicit job-stress was related to elevated cortisol only among
      anesthesiologists reporting large "mental distance" from work, which may
      represent limited job involvement related to burnout. Anesthesiologists with a
      low degree of job involvement who have high implicit job-stress associations have
      higher levels of waking salivary cortisol. Further studies are necessary to
      assess the impact of stress management techniques on anesthesiologists' personal
      and professional behavior as well as on the quality of medical care.

PMID- 22592186
TI  - Higher mortality among remote compared to rural or urban dwelling hemodialysis
      patients in the United States.
AB  - Living far away from specialized care centers is a potential barrier to the
      delivery of quality health care and has been associated with adverse outcomes. To
      assess mortality as a function of distance from the closest hemodialysis unit,
      and as a function of rural rather than urban residence, we analyzed prospectively
      collected data on 726,347 adults initiating chronic hemodialysis in the United
      States over a 13-year period. Participants were classified into categories of 0
      10 (referent), 11-25, 26-45, 46-100, and remote living over 100 miles from the
      closest hemodialysis unit. After a median follow-up of 2.7 years (range 0 to 12.7
      years), 368,569 patients died. Compared to the referent group, the adjusted
      hazard ratio of death was 1.01, 0.99, 0.96, and 1.21, respectively. When
      residence location was classified using rural-urban commuter areas, 16.5, 66.8,
      and 16.7% of patients lived in urban, micropolitan, and metropolitan areas,
      respectively. Compared with those living in metropolitan areas, the adjusted
      hazard ratio of mortality among patients residing in micropolitan and rural
      communities was 1.02 and 1.01, respectively. Thus, remote but not rural residence
      was associated with increased mortality among patients initiating chronic
      hemodialysis treatment in the United States.

PMID- 22592183
TI  - Overexpressions of RACK1 and CD147 associated with poor prognosis in stage T1
      pulmonary adenocarcinoma.
AB  - BACKGROUND: RACK1 has been shown to be able to interact with some key cellular
      proteins involved in tumor development and progression. Our study showed that the
      expressions of RACK1 and CD147 are correlated with each other. The purpose of
      this study is to clarify the relationship between expression of RACK1 and CD147
      in 180 patients with operable stage T1 human pulmonary adenocarcinoma and their
      clinicopathological features and prognostic significance. METHODS: DNA
      transfection and RNA interference of RACK1 were conducted to produce pulmonary
      adenocarcinoma cell lines with differential RACK1 expression. Western blot and RT
      PCR were used to quantify RACK1 and CD147 expression in protein and mRNA levels
      in pulmonary adenocarcinoma cell lines. Immunohistochemistry, double-labeling
      immunofluorescence, confocal laser scanning microscopy, and Western blot were
      used to correlate the clinicopathological significance of RACK1 and CD147
      expression in cases of stage T1 pulmonary adenocarcinoma. RESULTS: We detected
      high levels of RACK1 and CD147 mRNA as well as protein expression in pulmonary
      adenocarcinoma in vitro. In pulmonary adenocarcinoma, the expression of RACK1 and
      CD147 were correlated both in vitro and in vivo. Our clinicopathological analysis
      demonstrated that RACK1 or CD147 expression correlated with higher incidence of
      lymph node metastasis and lower differentiation than tumors that were negative
      for expression of either RACK1 or CD147. The expression of RACK1 and CD147 was
      not associated with the patient age or gender. Multivariate analysis demonstrated
      that the co-overexpression of RACK1 and CD147 was an independent prognostic
      factor for stage T1 pulmonary adenocarcinoma (P = 0.012). CONCLUSIONS: Tumor
      invasiveness is associated with expression of RACK1 and CD147 in pulmonary
      adenocarcinoma. The co-expression of RACK1 and CD147 could be an important
      prognostic biomarker for stage T1 pulmonary adenocarcinoma.

PMID- 22592187
TI  - Hemodialysis effect on platelet count and function and hemodialysis-associated
      thrombocytopenia.
AB  - Substantial activation of platelets can occur in the course of hemodialysis.
      Platelet surface markers show evidence of platelet degranulation. Some activation
      occurs due to exposure of blood to the roller pump segment and microbubbles may
      play a role. Platelet activation seems to be reduced with reused dialyzers or
      with those containing synthetic versus cellulosic membranes. Nevertheless, a
      substantial degree of platelet activation can be demonstrated with polysulfone
      and other synthetic membranes; the amount of activation may differ substantially
      among polysulfone membranes, depending on the manufacturer and the
      polyvinylpyrrolidone content. Platelet-platelet and platelet-leukocyte aggregates
      have been detected in the dialyzer blood outflow line and the consequences of
      these to the microcirculation are unknown. Typically, the platelet count
      decreases slightly during the first hour of dialysis, but mostly returns to
      initial values by the end of dialysis. A number of chronic hemodialysis patient
      cases have been reported in which a marked decrease in platelet count (50% or
      more) during dialysis was observed, resulting in mild degrees of predialysis
      thrombocytopenia. In only one case was the decrease in platelet count associated
      with bleeding. Dialyzer hypersensitivity symptoms are infrequently associated
      with a fall in platelet count. Most recent cases of dialysis-associated
      thrombocytopenia have been with polysulfone membranes, especially polysulfone
      membranes sterilized by electron beam. The exact cause of these reactions remains
      unknown.

PMID- 22592188
TI  - Moyamoya syndrome following growth hormone-secreting pituitary adenoma.
AB  - We report a case of Moyamoya syndrome developing in association with growth
      hormone-secreting pituitary adenoma. A 31-year-old female presented with
      acromegalic features. Magnetic resonance imaging revealed a 1 * 2 cm tumor in the
      sella turcica and MR angiography demonstrated unremarkable findings. Blood growth
      hormone and insulin-like growth factor I levels were elevated to 74.1 ng/ml and
      over 1 575 ng/ml, respectively. The diagnosis was growth hormone-secreting
      pituitary adenoma, and the tumor was removed through a transsphenoidal approach.
      Four years after surgery, she visited the outpatient department due to left side
      weakness for 2 months. Magnetic resonance images showed acute and old infarcted
      lesions in the basal ganglia and subcortical area and residual small pituitary
      adenoma in the sellar area. MR angiography demonstrated stenosis of the bilateral
      distal internal carotid arteries with basal collateral vessels. Conventional
      cerebral angiography showed complete obstruction in the right internal carotid
      artery and severe stenosis of the left internal carotid artery, middle cerebral
      artery, and anterior cerebral artery with basal collateral vessels. Her blood
      growth hormone and insulin-like growth factor I levels were 15.3 ng/ml and 1 055
      ng/ml, respectively. We believe that excess systemic exposures of growth hormone
      and insulin-like growth factor I may participate in the development of Moyamoya
      syndrome.

PMID- 22592189
TI  - Postoperative diabetes insipidus associated with pituitary apoplexy during
      pregnancy.
AB  - BACKGROUND: Pituitary apoplexy during pregnancy is so rare that only 15 cases (12
      pituitary adenomas, 2 lymphocytic neurohypophysitis, and 1 normal pituitary
      gland) have been published to date. Here, we report the case of a pregnant woman
      presenting with pituitary apoplexy from a nonfunctioning pituitary adenoma and
      provide a possible mechanism and management option for postoperative diabetes
      insipidus (DI). CASE PRESENTATION: A 26-year-old woman presented with sudden
      onset of headache and bitemporal hemianopsia in the 26th week of her first
      pregnancy. Magnetic resonance imaging clearly revealed an 18 mm pituitary mass
      with a fluid-fluid level component displacing the optic chiasma upward. Endonasal
      endoscopic transsphenoidal surgery was successfully carried out 7 days after the
      onset of symptoms. DI became apparent immediately after the operation and was not
      controllable by arginine vasopressin (AVP) but by 1-desamino-8-D-arginine
      vasopressin (DDAVP) instead. This finding suggests an association between DI and
      vasopressinase secretion from the placenta, because vasopressinase can degrade
      AVP but not DDAVP. DI had diminished by the time the patient delivered a healthy
      girl at the 40th week of gestation. CONCLUSION: Postoperative DI associated with
      pituitary apoplexy during pregnancy should be treated by DDAVP, which is not
      affected by placental vasopressinase secretion.

PMID- 22592190
TI  - Paradoxical surge of corticotropin after glucocorticoid replacement in central
      adrenal insufficiency.
AB  - A 78-yr-old man was admitted in emergency with fatigue, anorexia, vomiting,
      hypothermia (35.1  degrees C on a hot August day), hypotension (89/56 mmHg) and
      hyponatraemia (126 mEq/l). Plasma corticotropin and cortisol were severely
      depressed: 0.84 pmol/L and 33.1 nmol/L respectively (reference range, 1.5-13.9
      pmol/L and 110-505 nmol/L, respectively). Thyroid stimulating hormone was low
      normal and free-triiodothyronine and free-thyroxine were subnormal. Magnetic
      resonance imaging revealed swelling of the pituitary gland and the stalk. The
      patient recovered after glucocorticoid replacement (200 mg/day intravenous
      hydrocortisone on Day 1 followed by tapering). Central diabetes insipidus which
      had become apparent had been treated with 1-desamino-8-D-arginine vasopressin. A
      surge of corticotropin and cortisol, 19.4 pmol/L and 712.1 nmol/L respectively,
      was found on Day 5 when luteinizing hormone, follicle stimulating hormone, and
      testosterone were subnormal and prolactin was slightly elevated. Subsequently,
      corticotropin and cortisol levels normalized together with normalization of
      luteinizing hormone, follicle stimulating hormone, anti-diuretic hormone, thyroid
      stimulating hormone, prolactin, testosterone and thyroid hormone levels.
      Shrinkage of the pituitary gland occurred after one month. Serum immunoglobulin
      G4 was elevated (3.21 and 6.02 g/l at 1- and 3-month follow-ups respectively). In
      conclusion, a paradoxical surge of corticotropin after glucocorticoid replacement
      was observed in a patient with central adrenal insufficiency due to
      immunoglobulin G4-related hypophysitis. Surge of ACTH in central adrenal
      insufficiency after glucocorticoid replacement has rarely been reported, and this
      is the second such case report.

PMID- 22592191
TI  - Obstetrical prevention of human cancers. Review article.
AB  - Cancer appears in the new form of cell life as a direct consequence of self
      organising pre-cancer cells (dissipathogenic systems), whose further existence is
      disabled by extreme impairment of their metabolism. Life itself is the highest
      value, since instead of necrosis or apoptosis, the cellular system in an
      unfavourable environment can change its genetic identity provided that the
      improvement in its own metabolism leads to increased chaos by higher dissipation
      of matter and energy in its environment. Prolongation of human life has resulted
      by a longer period of old age which is favourable for self-organisation of
      dissipative neoplastic cells. Modern medicine has explained the relation of the
      cervical cancer to preterm births and to inadequate use of oral contraceptives
      and/or replacement, instead of supplementary, neurohormonal therapy. Therefore,
      as early as in the period of pregnancy reproductive cells should be protected due
      to their prime importance in the intergenerational passage of life. Disturbance
      of systemic autoregulation causes development of dissipathogenic state of cells.
      A single zygote, whose environment is also important for the future development
      of the next two generations that are initiated with its formation, defines the
      unique identity of each person, whose life is determined by free will and
      neoplasms.

PMID- 22592192
TI  - Effects of acute stressors on the expression of oxytocin receptor mRNA in hearts
      of rats with different activity of HPA axis.
AB  - OBJECTIVES: Cardiovascular system is regulated by a diverse array of hormones,
      neurotransmitters and neuropeptides. Oxytocin and its receptors (OTR) were also
      shown to regulate cardiovascular functions and this hormone was even called
      cardiovascular hormone. In recent publication, we demonstrated the expression of
      mRNA of OTR by real-time quantitative PCR (RT qPCR) in all rat heart
      compartments. The aim of this study was to investigate the effects of acute
      restraint stress on OTR mRNA expression in two rat strains with different
      activity of HPA axis. METHODS: Adult male Sprague-Dawley and Lewis rats, the
      latter strain reported to have lower HPA activity, were used in RT qPCR studies
      and Wistar rats in immunofluorescent ones. Both acute restraint (IS) and this
      stress combined with the immersion of rats in water (ICS) lasted 60 min. Gene
      expression of OTR mRNA was estimated in all heart compartments after 1 or 3 hours
      after stress termination (IS1, IS3, ICS1, ICS3). The relative expression was
      calculated using 2(-DeltaDeltaC)T method. In immunofluorescent studies we used
      commercial specific OTR antibodies. RESULTS: In RT qPCR studies we found higher
      expression of OTR mRNA in atria than in ventricles and no statistical differences
      between Sprague-Dawley and Lewis rats under basal conditions. Relative expression
      of OTR mRNA after 60 min lasting stress exposure differed in dependence on the
      stress type and partly on the time interval after the stress termination. When
      compared to controls, in rat left atria both stressors caused inhibition of OTR
      mRNA expression in both rat strains. In rat ventricles, which have very low OTR
      mRNA expression, there was a significant difference in the effect of two
      stressors. In most groups ICS displayed the increase of OTR mRNA expression if
      compared to IS groups. Immunofluorescent studies revealed changes induced by
      acute restraint stress in all heart compartments. The immunofluorescent studies
      suggested that acute stress induces higher colocalization of OTR with the nuclei
      than it was observed in the controls. CONCLUSIONS: The expression of OTR mRNA in
      all heart compartments of controls as well as after stress exposure in Sprague
      Dawley and Lewis rats support the notion that OTR plays a regulatory role in the
      cardiovascular system and is also involved in the regulations in the heart after
      stress. The immunofluorescent observation that OTRs coexpress in areas of cell
      nuclei in certain heart compartments and after acute stress, compared to
      controls, requires further studies.

PMID- 22592193
TI  - An active product of cruciferous vegetables, 3,3'-diindolylmethane, inhibits
      invasive properties of extravillous cytotrophoblastic cells.
AB  - OBJECTIVES: During implantation, human trophoblastic cells have to proliferate,
      migrate and invade pregnant uterus. A natural product of cruciferous vegetables,
      3,3'-diindolylmethane (DIM), is known to induce some stress response genes (such
      as glucose-regulated protein 78 kDa (GRP78)) and to have anti-invasive and pro
      apoptotic effects on tumor cells. Therefore, we have investigated the potential
      effect of DIM on invasive extravillous cytotrophoblasts (evCTBs) cells. MATERIALS
      AND METHODS: evCTBs were purified from first trimester trophoblasts and cultured
      in presence or not of DIM for 48h. In order to evaluate invasive properties of
      cells, they were seeded on collagen-coated insert following boyden chamber
      principle and matrix metalloproteinases (MMPs) and GRP78 expression was evaluated
      by qPCR. RESULTS: We showed that DIM decreases (p=0.013) invasive properties of
      evCTBs. In parallel, we determined that MMP-2, -7 and -9 which are involved in
      evCTBs invasion and known to be regulated by DIM, are not affected by DIM in
      evCTBs. In contrast, MMP-1 mRNA is induced (p=0.03) and MMP-12 is decreased
      (p=0.01) in DIM treated cells. Moreover, DIM treatment does not affect GRP78 mRNA
      expression in evCTBs. CONCLUSIONS: Collectively, the present results provide
      evidence that DIM does not impact evenly on evCTBs and cancer cells.

PMID- 22592195
TI  - Fetal macrosomia--an obstetrician's nightmare?
AB  - OBJECTIVES: Fetal macrosomia is defined as a fetus that is of large size for
      gestational age, i.e. equal to or greater than the 90th percentile of weight.
      There is some evidence of increased perinatal mortality and morbidity rates in
      cases of macrosomia. DESIGN: This is a retrospective study of patients with term
      pregnancy. We analyzed the deliveries of 508 infants born with birth weight >= 4
      200 grams and considered them as a study group. The deliveries of newborns with
      birth weight less than 4 000 g constituted the control group (330 cases).
      Maternal and neonatal medical records were retrospectively reviewed for clinical
      data. SETTING: The study was conducted in Second Department of Obstetrics and
      Gynecology Warsaw Medical University from January 2004 to December 2007. RESULTS:
      Maternal age, parity, BMI and pregnancy weight gain were positively related to
      fetal macrosomia. Prolonged first stage of labor, cesarean section rate and
      increased blood loss were observed more frequent in macrososmia. There were no
      differences between both groups according to Apgar score and neonatal birth
      trauma. Macrosomia was observed more frequent in male fetuses. Our data showed
      that careful qualification to way of delivery let us achieve the same good
      outcome in macrosomia. CONCLUSIONS: Older obese multiparas are at increased risk
      of having macrosomic baby. The increased incidence of cesarean section in these
      women is due to cephalo-pelvic disproportion or obstructed labor. Macrosomia is
      more often in male fetuses.

PMID- 22592194
TI  - The evaluation of estradiol and leptin action on the activity of the somatotropic
      and gonadotropic axes in peripubertal female rats.
AB  - OBJECTIVE: Available data suggest that estrogens and leptin play a role in the
      control of the pubertal process. In humans and some mammal species the increase
      of the activity of gonadotropic axis accompanies the decrease in the rate of
      growth at puberty. The effect of 17beta-estradiol and/or leptin administration on
      the somatotropic and gonadotropic axes was studied using prepubertal female rats
      as an animal model. MATERIAL AND METHODS: Prepubertal female rats received
      estradiol/saline, estradiol/leptin, oil/leptin or oil/saline (vehicles)
      respectively. The changes of growth rate, and serum 17beta-estradiol, leptin, GH,
      IGF-I and gonadotropins levels as well as LHRH and estrogen receptor (ER)
      concentrations in the medial basal hypothalamus (MBH) and the pituitary were
      determined. All hormones concentrations were measured by radioimmunoassay and ER
      by radioligand methods . RESULTS: In estradiol and/or leptin treated animals
      noticeable reduction of rate of growth was found. The decrease of growth in
      response to estradiol treatment accompanied the increase GH level and the
      decrease of IGF-I concentration in the circulation. Both hormones operating
      together activated reproductive axis, what was manifested by a significant
      increase of LHRH abundant in the hypothalamus as well as elevated LH and FSH
      levels in the circulation. In these rats a significant decrease of the estrogen
      receptor concentrations in the pituitary was observed. CONCLUSION: The role of
      estradiol and leptin in the control of growth and reproduction seems to overlap
      only partially. Estradiol plays a significant role in the activation of the
      reproductive axis, and leptin takes part as a permissive factor in pubertal
      process.

PMID- 22592196
TI  - Heart rate variability spectral analysis in patients with panic disorder compared
      with healthy controls.
AB  - OBJECTIVES: The aim of our study is to measure very low frequency band (VLF), low
      frequency band (LF) and high frequency band (HF) components of R-R interval
      during orthostatic test in patients with panic disorder and a comparison with
      healthy controls. METHODS: We measured HRV in 31 patients with panic disorder and
      20 healthy controls. Diagnosis was done according to the ICD-10 research
      diagnostic criteria confirmed with MINI (MINI international neuropsychiatric
      interview). Autonomic nervous system (ANS) has been evaluated during orthostatic
      change in three positions. Intensity of symptoms was assessed using psychiatric
      scales. RESULTS: There were highly statistically significant differences between
      panic patients and control group in all components of power spectral analysis in
      2nd and 3rd VLF components and in HF components of 2nd. We have found highly
      statistically significant negative correlations between level of dissociation
      measured by DES and some parameters of ANS. We found negative correlations
      between the age of the patient and activity of ANS, and negative correlations
      between activity of ANS and duration and onset of disorder and dosage of
      antidepressants. CONCLUSION: These findings demonstrate a lower parasympathetic
      activity and higher sympathetic/parasympathetic ratio in panic disorder patients
      measured during the changes of postural position in comparison with healthy
      controls. Autonomic dysregulation is associated with panic disorder and has the
      relation with the level of dissociation, the age of patiens and age of onset of
      disorder.

PMID- 22592197
TI  - Acute consciousness disorders in intensive care medicine - value of its grading
      for prognostic conclusion.
AB  - OBJECTIVES: To understand consciousness we have to understand the mechanism of
      its function, which is to effectively organize sensory inputs from our
      environment. Consciousness is the basic, essential outcome of the process of
      organizing these sensory inputs, resulting in cognitive, mental, emotional,
      executive, instinctual or other marginally aware states. This reciprocal process
      of the CNS implies that organization is an act, which precedes consciousness,
      i.e. preconscious function. Most scientific explanations portray consciousness as
      an "emergent property" of classical computer-like activities in the brains neural
      networks. Doctors at ICU work daily with patients with altered human
      consciousness. Therefore, they must recognize and manage it skilfully and use
      adequate approaches for definite solutions. MATERIAL AND METHODS: We observed a
      series of patients with traumatic and non traumatic brain injuries admitted to
      the ICU. The quality of life of these patients during the course of intensive
      care was very elementary and the final outcome GCS (oGCS) for future life was
      defined as a comatose state or apallic state, very rarely was it restored to
      premorbid condition as far as lucidity, attention, cognition, and executive
      functions. RESULTS: We found that a significant oGCS increase in relation to
      condition at admission or intake GCS (iGCS) in the group with 184 patients total
      (p<0.00001), in cardio-pulmonary resuscitation (CPR), traumatic brain injury
      (TBI) subgroups (p<0.00001) and in spontaneous haemorrhage (SH) (p<0.05)
      represents the only basic prerequisite for further improvement. It is not easy to
      find good therapeutic approaches after traumatic and non traumatic brain injury.
      A statistically significant oGCS increase in relation to iGCS due to quite
      intense medical care and keeping disclosed the state of unconsciousness with
      further probable evolution through the following possible ways: death in fluent
      comatose state, delirium and awakening, delirium ending in death, direct
      awakening from comatose state. Therefore significantly increased oGCS is the only
      basic prerequisite for pragmatically optimal "quality of life" in the course of
      later life. CONCLUSION: We raise general questions for both scientists and
      clinicians that will assist in their efforts to understand the basic endogenous
      conscious biological processes, their pathological changes and the links between
      them.

PMID- 22592198
TI  - Nerve growth factor increases electrical activity of neural cells derived from
      murine bone marrow stromal cells.
AB  - OBJECTIVE: Nerve growth factor (NGF) triggers long-term neuronal excitability. We
      examined its effect on murine bone marrow stromal cells (BMSC)-derived neurons.
      METHODS: With an optimal differentiation protocol, BMSCs were differentiated into
      neurons in culture. To confirm the probability of differentiation of BMSC into
      neuron, the expression of neuronal marker protein, neurofilament, was examined by
      immunocytochemistry. To examine the electrophysiological properties of BMSC
      derived neurons, the field potentials were recorded either from nontreated
      (control) BMSC-derived neurons or from BMSC-derived neurons after the treatment
      with NGF by using extracellular recording techniques. RESULTS: Most BMSC-derived
      neurons showed spontaneous discharges whose amplitudes were up to 2 mV. When NGF
      at a concentration of 100 ng/ml was applied to BMSC-derived neurons, the
      amplitudes of discrete field potentials were gradually enlarged within 1 min
      after NGF application and peaked 3 min later (20-fold the size of control).
      However, the enlargement of the amplitudes of field potentials almost disappeared
      5 min after NGF application. CONCLUSION: This finding indicates that neuronal
      cells derived from murine BMSCs generate discrete field potential activities
      spontaneously and that NGF has the effect of enlarging transient, but not
      sustained, electrical activity of BMSC-derived neurons.

PMID- 22592199
TI  - Genomic copy number variations: A breakthrough in our knowledge on schizophrenia
      etiology?
AB  - OBJECTIVES: The term "copy number variation/variant" (CNV) denotes a DNA sequence
      with a magnitude of 1 kb at least which is differently represented among
      individuals based on its deletion or duplication. Since 2008, multiple studies
      have reported copy number variations in schizophrenia, and they seem to fill in a
      gap in our knowledge on the genetic background of schizophrenia. The aim of this
      review is to sum up the current findings related to CNVs in schizophrenia in
      order to facilitate further research. METHODS: We searched the PubMed computer
      database using the key words "schizophrenia AND CNVs" on 26th October 2011. Out
      of 91 obtained results, we selected the references based on their relevance.
      RESULTS: The CNVs at genome loci 1q21.1, 2p16.3, 3q29, 15q11.2, 15q13.3, 16p13.1
      and 22q11.2 were associated with schizophrenia most frequently. The data provide
      evidence for low prevalent, but highly penetrant CNVs associated with
      schizophrenia. CNV deletions show higher penetrance than duplications. Larger
      CNVs often have higher penetrance than smaller CNVs. Although the vast majority
      of CNVs are inherited, CNVs that have newly occurred as de novo mutations have
      more readily been implicated in schizophrenia. De novo CNVs may be responsible
      for the presence of schizophrenia in only one of the two monozygotic twins, who
      otherwise have identical genomes. CONCLUSION: Identifying CNVs in schizophrenia
      can lead to changes in the treatment and genetic counselling. Our knowledge on
      the genetic background of neurodevelopmental disorders may also reduce stigma in
      schizophrenia.

PMID- 22592200
TI  - The analysis of exogenous ghrelin plasma activity and tissue distribution.
AB  - OBJECTIVES: Ghrelin presents a multiplicity of biological functions, what is
      consistent with widespread expression of this peptide and its receptors. Ghrelin
      may act locally, but it may also influence distant cells. The aim of the study
      was to assess plasma activity of exogenous ghrelin and its distribution in rats.
      DESIGN: Plasma radioactivity of (125)I-ghrelin (cpm) was analyzed in blood
      specimens collected after (125)I-ghrelin administration. Tissue uptake of (125)I
      ghrelin (cpm/mg) was evaluated in 27 tissues obtained during an autopsy performed
      1, 2 and four hours after (125)I-ghrelin administration. The radioactivity of the
      tissue specimen (cpm) was divided by the weight of the specimen (mg). RESULTS:
      Plasma (125)I-ghrelin radioactivity decreased rapidly after peptide
      administration. The half-life time of (125)I-ghrelin was 15-18 minutes. The
      analysis of (125)I-ghrelin distribution revealed three profiles of its tissue
      uptake. The first profile was characterized by decreasing radioactivity (e.g.
      brain, kidney, liver). Increasing tissue radioactivity followed by a gradual
      decrease (second profile) was observed for example in stomach, intestine and
      thyroid. The third profile was described as a relatively stable radioactivity
      (e.g. lung, myocardium). Despite of Lugol's solution administration, thyroid
      uptake of (125)I-ghrelin was notably higher than in other tissues (second and
      third profile). CONCLUSIONS: Exogenous ghrelin uptake in tissues that produce
      this peptide suggests, that ghrelin influences the biology and function of these
      cells also in endocrine way. Similarly, the accumulation of peptide observed in
      the third profile (e.g. thyroid) may reflect a potential role of ghrelin in these
      organs.

PMID- 22592201
TI  - The association of heart rate variability examined in supine and standing
      position with ambulatory blood pressure monitoring in anorexia nervosa.
AB  - OBJECTIVE: To evaluate the association of heart rate variability (HRV) examined
      in supine and standing position with ambulatory blood pressure monitoring (ABPM)
      in patients with anorexia nervosa (AN). METHODS: HRV in supine and standing
      position and ABPM were examined in 30 AN patients and 30 control subjects. The
      correlations between HRV and ABPM were evaluated. RESULTS: The average age was
      25+/-5 in AN patients and 25+/-4 years in controls (NS). LF (low frequency) power
      in AN patients and controls was comparable in supine position. LF power
      significantly increased during standing in controls, but no increment was
      detected in AN patients. The HF (high frequency) power was significantly
      increased in AN patients in supine position, but after standing was comparable
      with controls. The ratio LF/HF was lower both in supine and standing position in
      AN patients but the differences did not reach statistical significance. Blood
      pressure values in AN patients were comparable with controls in supine position
      but were significantly lower in standing position. Ambulatory blood pressure
      values were significantly lower in AN patients during active but not sleeping
      period. In standing position HF and LF powers positively and LF/HF negatively
      correlated with ABPM blood pressure values during active period in controls while
      in AN patients only LF power correlated with diastolic and mean blood pressures.
      CONCLUSION: The lower ABPM values in AN patients during active period in
      comparison with control subjects may be explained by HRV changes, mainly by its
      impaired relations with blood pressure in standing position.

PMID- 22592202
TI  - Is there a correlation between ADHD symptom expression between parents and
      children?
AB  - BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is one of the most
      common mental health disorders in childhood; symptoms persist into adulthood in a
      majority of patients. It is among the most heritable of psychiatric disorders
      with a high risk for familial aggregation and has been linked in adulthood with
      impairment across a variety of domains, including parenting. Parental gender,
      ADHD status and symptom expression could be related to the severity of ADHD
      symptoms in the child. METHODS: We used prospective, observational study of
      clinical group of 30 children with diagnosed ADHD and control group of 37 healthy
      subjects. Only children with both biological parents available were included.
      Data on ADHD symptomatology for all subjects was gathered by a set of clinical
      tools (CBCL1991, TRF1991, WURS, self-report scale modified from DSM IV). Under
      the assumption that ADHD is a dimensional disorder, raw scores from
      questionnaires were used as they display the complete range of values. RESULTS:
      Clinical group showed higher values in all areas of children symptomatology, the
      same was observed for parental ADHD symptomatology. Significant correlation was
      found between children and paternal current ADHD symptomatology in the clinical
      group. This was not confirmed for mothers. CONCLUSION: Our study stresses an
      importance of screening for ADHD symptoms in parents of clinically referred
      children with ADHD as the correlation between severity of paternal and child's
      ADHD symptoms was confirmed. Our results stress the importance of including the
      father into the clinical assessment.

PMID- 22592203
TI  - The relationship between S100B protein serum levels, injury severity and Glasgow
      Outcome Scale values in children with CNS injuries.
AB  - OBJECTIVES: The S100B protein subgroup is a thermolabile acidic calcium-binding
      protein, which was first described in association with the central nervous
      system. Destruction of nerve tissue results in S100B protein release from
      astrocytes and elevation of its levels in cerebrospinal fluid. If the blood-brain
      barrier is also damaged, S100B can pass into the systemic circulation and
      elevated blood levels of S100B can be detected. High S100B serum levels in
      patients with head injuries are predictive of possible development of secondary
      brain injury and may be related to the extent of permanent injury to the CNS .
      MATERIAL AND METHODS: The authors present results obtained from a group of 39
      children aged 0 (newborns) to 17 years with an isolated craniocerebral injury.
      RESULTS: In our group of 39 children (aged 0-17 years) we observed excellent GOS
      group (GOS - Glasgow Outcome Scale 4 or 5) in 33 patients at the time of transfer
      from our intensive care unit to the neurological department. There were no deaths
      and only 6 children were in the poor GOS group (GOS 2 or 3). A second GOS
      evaluation was performed 6 months later: at this time 36 children were in the
      excellent GOS group and only 3 children remained in the poor GOS group.
      CONCLUSIONS: Due to high variability in S100B protein serum levels in children
      (dependent on age and gender) no correlation between initial S100B levels and GOS
      was observed for our group of patients. Our results indicate that the rate of
      decrease of S100B protein levels back to normal values is more meaningful than
      its absolute value.

PMID- 22592204
TI  - Clinical value of real time 3D sonohysterography and 2D sonohysterography in
      comparison to hysteroscopy with subsequent histopathological examination in
      perimenopausal women with abnormal uterine bleeding.
AB  - OBJECTIVE: In many publications the transvaginal ultrasound is regarded as the
      first step to diagnose the cause of uterine bleeding in perimenopausal women. In
      order to improve the sensitivity and specificity of the conventional ultrasound
      physiological saline solution was administered to the uterine cavity and after
      expansion of its walls the interior uterine cavity was examined. And this
      procedure is called 2D sonohysterography (SIS 2D). By the ultrasound scanners
      which enable to get 3D real time image a spatial evaluation of the uterine cavity
      is possible. Clinical value of the real time 3D sonohysterography and 2D
      sonohysterography compared to hysteroscopy with histopathological examination in
      perimenopausal women. MATERIAL AND METHODS: The study concerned a group of 97
      perimenopausal women with abnormal uterine bleeding. In all of them after a
      standard transvaginal ultrasonography a catheter was inserted into the uterine
      cavity. After expansion of the uterine walls by administering about 10 ml of 0,9%
      saline solution the uterine cavity was examined by conventional
      sonohysterography. Then a 3D imaging mode was activated and the uterine interior
      was examined by real time 3D ultrasonography. The ultrasound results were
      verified by hysteroscopy, the endometrial lesions were removed and underwent a
      histopathological examination. RESULTS: In two cases the SIS examination was
      impossible because of uterine cervix atresion. In the rest of examined group the
      SIS 2D sensitivity and specificity came up to 72 and 96% respectively. In the
      group of SIS 3D the sensitivity and specificity reached 83 and 99% respectively.
      CONCLUSIONS: Adding SIS 3D, a minimally invasive method, to conventional
      sonohysterography improves the precision of diagnosis of endometrial pathology,
      allows to get three-dimensional image of the uterine cavity and enables
      examination of endometrial lesions. The diagnostic precision of this procedure is
      similar to the results achieved by hysteroscopy.

PMID- 22592205
TI  - Adiponectin to leptin index as a marker of endometrial cancer in postmenopausal
      women with abnormal vaginal bleeding: an observational study.
AB  - OBJECTIVES: To evaluate the correlation between endometrial cancer and
      adiponectin plasma concentration, leptin plasma concentration as well as
      adiponectin to leptin index in the population of postmenopausal women with
      abnormal vaginal bleeding. DESIGN: An observational study SETTINg: Department of
      Gynecology and Obstetrics, Specialist Teaching Hospital in Tychy, Poland.
      Population. 99 women between 47 and 88 years old, in postmenopausal state.
      METHODS: The cases (54 women) were females hospitalized due to postmenopausal
      vaginal bleeding in whom dilation and curettage (D&C) was performed and
      endometrial intraepithelial neoplasia (EIN) was diagnosed in anathomopathology.
      Hysterectomy was then performed in all cases and the endometrial cancer diagnosis
      was confirmed. The controls (45 women) consists of females with no postmenopausal
      uterine bleeding in whom endometrial thickness in transvaginal ultrasound was
      greater than 5 mm. D&C was than performed and no endometrial neoplasia was
      detected in any of the subjects. Adiponectin and leptin plasma concentration was
      measured in both groups. Mein outcome measures. The area under the curve,
      sensitivity, specificity and cutoffs for adiponectin, leptin and adiponectin to
      leptin index. RESULTS: Adiponectin, leptin and adiponectin to leptin index were
      statistically correlated with the risk of endometrial cancer. At the suggested
      cutoffs, corresponding to the highest accuracy (minimal false-negative and false
      positive results), adiponectin to leptin index resulted in the highest
      sensitivity and specificity compared to adiponectin and leptin alone.
      CONCLUSIONS: Adiponectin to leptin index due to the highest sensitivity and
      specificity may be used as a marker of endometrial cancer in postmenopausal women
      with abnormal vaginal bleeding.

PMID- 22592206
TI  - The relation of cortisol and sex hormone levels to results of psychological,
      performance, IQ and memory tests in military men and women.
AB  - BACKGROUND: Cortisol, along with other hormones of hypothalamo-pituitary-adrenal
      axis, belongs to one of the main factors influencing psychological and
      pathognomic factors, intelligence, and memory. METHODS: The aim of our study was
      to review a large battery of psychological, performance, IQ and memory tests as
      to their relation with cortisol, testosterone and estrogen levels in groups of
      100 men and 93 women who attended the Central Military Hospital in Prague for
      regular entrance psychological examinations for military personnel. RESULTS: In
      men, we detected positive correlations between cortisol and emotional lability,
      and negative correlations with impulsivity, while in women hypochondria and
      psychopathology were negatively correlated, and aggression measured with the
      Meili selective memory test had a positive relation to cortisol level.
      Testosterone correlated positively with emotional liability and negatively with
      impulsivity in men, and negatively with hypochondria and psychasteny, indirect
      aggression, irritability and paranoia in women. Estradiol correlated positively
      with psychopathology in men, and negatively with phobia. It was positively
      correlated with negativism in women. No clear correlation was observed between
      the concentration of steroid hormones and psychomotor performance or
      intelligence. CONCLUSIONS: Concentrations of steroid hormones correlate with
      results of several psychological tests, the sign and magnitude of these
      correlations, however, very often differ in military men and women.

PMID- 22592207
TI  - Relevance of CYP2D6 variability in first-episode schizophrenia patients treated
      with risperidone.
AB  - OBJECTIVE: The objective of this prospective, naturalistic study, conducted in
      first-episode psychosis patients from a Central-European population, was to
      assess the utility of Cytochrome P-450 2D6 (CYP2D6) genotype testing under normal
      clinical setting. METHODS: A total of 35 patients diagnosed for the first time
      with schizophrenia or acute schizophrenia-like psychotic disorder and treated
      with risperidone were enrolled in the study. These patients underwent
      sequentiation of the CYP2D6 gene and evaluations of symptoms and severity of
      adverse effects using the PANSS and UKU scales, respectively. Doses of
      antipsychotics and other co-medication were monitored as well. In statistical
      analysis, Fisher's exact test was used to compare ratios and the Wilcoxon rank
      sum test was used in the comparison of continual variables. RESULTS: PM patients
      showed a significantly lower reduction in psychotic symptoms and a greater
      severity of psychotic symptoms following risperidone treatment and higher doses
      of antipsychotics not metabolized by CYP2D6, which were used as co-medication.
      CONCLUSIONS: Based on these results, patients with the PM genotype experiencing
      first-episode schizophrenia don't appear to be optimal recipients of risperidone
      treatment. However, as the main limitation of this study was the relatively small
      sample-size, replication with a larger scale study is needed to confirm these
      findings.

PMID- 22592208
TI  - Geometric and harmonic study of the aging of the fourth rib.
AB  - One of the current reference methods, namely the Iscan method for estimating age
      at death, consists in the subjective observation of the sternal end of the fourth
      rib. In this study, we looked to identify the morphometric characteristics of the
      sternal end of the fourth rib that were most affected by aging by measuring them
      in an objective way. For this purpose, we collected measurements from the fourth
      rib tip of 414 French males and used mathematical algorithms derived from pattern
      recognition and signal processing to identify variables that reflect both
      geometric characteristics and serration patterns of the ribs. Completed analysis
      was carried out on the 284 ribs for which all the variables could be collected.
      We showed that the three least collinear variables that best explain age
      objectively are the postero-superior pit depth, the fine serrations of the ovoid
      (delineating the pit shape), and its posterior flaring. This work provides a
      useful basis for subsequent studies on aging and age prediction.

PMID- 22592209
TI  - Determining sex by bone volume from 3D images: discriminating analysis of the
      tali and radii in a contemporary Spanish reference collection.
AB  - The discriminant power of bone volume for determining sex has not been possible
      to determine due to the difficulty in its calculation. At present, new
      advancements based on 3D technology make it possible to reproduce the bone
      digitally and calculate its volume using computerized tools, which opens up a new
      window to ascertaining the discriminant power of this variable. With this
      objective in mind, the tali and radii of 101 individuals (48 males and 53
      females) of a contemporary Spanish reference collection (twentieth century) (EML
      1) were scanned using the Picza 3D Laser Scanner. Calculated for the tali were
      total volume, the volume of the posterior region, which includes the posterior
      calcaneal facet and other three volumes of the anterior region. Calculated for
      the radius were total volume, volume of the radius head, volume of the diaphysis,
      and volume of the distal end. The data are presented for all of the variables,
      distinguishing between the right and left side. The data were processed using the
      statistical program PASW Statistics 18, thereby obtaining classification
      functions for sex which accurately classify 90.9 % of tali and 93.9 % of radii on
      the basis of their total left and right volume, respectively. Studying the volume
      in different regions of the bone shows that the diaphysis of the right radius
      possesses a high level of discriminant power, offering classification functions
      which accurately classify 96.9 % of the sample. The validation test performed on
      a sample of 20 individuals from another contemporary Spanish reference collection
      (EML 2) confirms the high discriminant power of the volume obtaining an accurate
      classification rate of 80-95 % depending on the variable studied.

PMID- 22592210
TI  - Predictors of death, local recurrence, and distant metastasis in completely
      resected pathological stage-I non-small-cell lung cancer.
AB  - OBJECTIVE: This study investigated the factors predicting recurrence and death in
      patients with resected stage-I non-small-cell lung cancers according to the 7th
      edition of tumor, node, metastasis (TNM) classification for lung cancer. METHODS:
      All patients undergoing surgical resection for pathological stage-I non-small
      cell lung cancers at Taipei Veterans General Hospital between 1980 and 2000 were
      retrospectively reviewed. Those undergoing sublobar resection were excluded. The
      factors predicting overall survival (OS), overall recurrence, local recurrence,
      and distant metastasis were investigated. RESULTS: A total of 756 patients were
      eligible. The 5-year OS rate and probability of freedom from recurrence were
      57.3% and 70.2%, respectively. The 2-year local-recurrence-free and distant
      metastasis-free rates were 90.7% and 82.1%, respectively. In multivariable
      analysis, the new T descriptor (T1a, T1b, and T2a) was the common factor that
      significantly affected OS (p = 0.003), overall recurrence (p = 0.004), and
      distant metastasis (p < 0.001). Smoking index more than 20, and number of
      mediastinal lymph nodes dissected/sampled of 15 or fewer were common factors that
      significantly predicted worse OS (p < 0.001, p < 0.001, respectively), lower
      probability of freedom from overall recurrence (p = 0.025, p = 0.009,
      respectively), and higher risk of local recurrence (p < 0.001, p = 0.030,
      respectively). Non-squamous-cell histology predicted higher risk of distant
      metastasis (p = 0.006). CONCLUSIONS: Risks of death and recurrence increase as
      the T descriptor upgrades in the new TNM system. The combination of risk factors
      can be used to identify high-risk subgroups of local recurrence and distant
      metastasis.

PMID- 22592211
TI  - MicroRNA-381 represses ID1 and is deregulated in lung adenocarcinoma.
AB  - INTRODUCTION: MicroRNAs are small, noncoding RNAs that suppress gene expression
      by binding to the 3' untranslated region (UTR) and thereby repress translation or
      decrease messenger RNA stability. Inhibitor of differentiation 1 (ID1) is a
      putative stem-cell gene involved in invasion and angiogenesis. We previously
      showed that ID1 is regulated by Src kinases, overexpressed in human lung
      adenocarcinoma, and targeted by Src-dependent microRNAs. The current study
      focused on the association between miR-381 and ID1 in lung adenocarcinoma.
      METHODS: An ID1 3'UTR-luciferase reporter assay was used to determine whether miR
      381 directly targets ID1. Human lung cancer cell lines were stably transduced
      with a precursor of miR-381 to evaluate its role on ID1 expression and to
      investigate changes in cell migration and invasion. The Src tyrosine kinase
      inhibitors saracatinib and dasatinib were used to repress ID1 expression. MiR-381
      expression was measured in 18 human lung adenocarcinomas and corresponding normal
      lung tissue by quantitative reverse-transcription polymerase chain reaction.
      RESULTS: ID1 is a direct target of miR-381 as shown by 3'UTR luciferase reporter
      assays. MiR-381 expression was negatively correlated with ID1 expression in lung
      cancer cell lines. Ectopic expression of miR-381 reduced ID1 mRNA and protein
      levels, and significantly decreased cell migration and invasion. Furthermore, miR
      381 was significantly downregulated in human lung adenocarcinomas, and low miR
      381 expression levels correlated with poor prognosis. CONCLUSION: These results
      suggest that downregulation of miR-381 and thus induction of its target ID1 may
      contribute to the metastatic potential of lung adenocarcinomas. Further studies
      to explore potential therapeutic strategies, including Src inhibitors, are
      ongoing.

PMID- 22592212
TI  - Hsp90 inhibition overcomes HGF-triggering resistance to EGFR-TKIs in EGFR-mutant
      lung cancer by decreasing client protein expression and angiogenesis.
AB  - INTRODUCTION: The three major clinically relevant mechanisms of acquired
      resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
      (TKIs) in EGFR mutant lung cancer are a second mutation in the EGFR gene (T790M),
      Met amplification, and increased expression of hepatocyte growth factor (HGF).
      Heat shock protein90 (Hsp90) is a 90 kDa molecular chaperone for proteins that
      include EGFR, Met, and echinoderm microtubule-associated proetin-like-4-the
      anaplastic lymphoma kinase. Here, we determined whether inhibition of Hsp90 could
      overcome HGF-triggered EGFR-TKI resistance in EGFR mutant lung cancer cells.
      METHODS: The effects of the Hsp90 inhibitor 17-demethoxygeldanamycin (17-DMAG) on
      the growth of lung cancer cells resistant to the EGFR-TKI were examined in the
      presence and absence of HGF, and in cells transfected with the HGF gene in vitro
      and in vivo. RESULTS: EGFR-TKI erlotinib did not inhibit the growth of HGF-gene
      transfected Ma-1 (Ma-1/HGF) cells and H1975 cells, containing the EGFR L858R and
      T790M mutations, respectively. Erlotinib also did not inhibit the growth of PC-9
      and Ma-1 cells, with deletions in EGFR exon19, in the presence of HGF. However,
      17-DMAG induced apoptosis and markedly inhibited the growth of these cell lines,
      even in the presence of HGF. This inhibition by 17-DMAG was associated with
      decreased expression of EGFR and Met in tumor cells. An in vivo model of HGF
      triggered erlotinib-resistance, which used Ma-1/HGF cells, showed that 17-DMAG
      markedly suppressed tumor growth by decreasing angiogenesis and increasing
      apoptosis. CONCLUSIONS: Hsp90 inhibitors may overcome HGF-triggered resistance to
      EGFR-TKIs and may result in more successful treatment of patients with EGFR
      mutant lung cancers.

PMID- 22592213
TI  - Resection rate and outcome of pulmonary resections for non-small-cell lung
      cancer: a nationwide study from Iceland.
AB  - BACKGROUND: The proportion of patients with non-small-cell lung cancer (NSCLC)
      who undergo surgery with curative intent is one measure of effectiveness in
      treating lung cancer. To the best of our knowledge, surgical resection rate (SRR)
      for a whole nation has never been reported before. We studied the SRR and
      surgical outcome of NSCLC patients in Iceland during a recent 15-year period.
      METHODS: This was a retrospective study of all pulmonary resections performed
      with curative intent for NSCLC in Iceland from 1994 to 2008. Information was
      retrieved from medical records and from the Icelandic Cancer Registry. Patient
      demographics, postoperative tumor, node, metastasis stage, overall survival, and
      complication rates were compared over three 5-year periods. RESULTS: Of 1530
      confirmed cases of NSCLC, 404 were resected, giving an SRR of 26.4%, which did
      not change significantly during the study period. Minor and major complication
      rates were 37.4% and 8.7%, respectively. Operative mortality rates were 0.7% for
      lobectomy, 3.3% for pneumonectomy, and 0% for lesser resection. Five-year
      survival after all procedures was 40.7% and improved from the first to the last 5
      year period (34.8% versus 43.8%, p = 0.04). Five-year survival for stages I and
      II together was 46.8%, with no significant change in stage distribution between
      periods. Five-year survival after pneumonectomy was 22.0%, which was
      significantly lower than for lobectomy (44.6%) and lesser resection (40.7%) (p <
      0.005). Unoperated patients had a 5-year survival of 4.8%, as compared to 12.4%
      for all the NSCLC patients together. CONCLUSION: Compared with most other
      published studies, the SRR of NSCLC in Iceland is high. Short-term outcome is
      good, with a low rate of major complications and an operative mortality of only
      1.0%. Five-year survival improved significantly over the study period.

PMID- 22592214
TI  - Sedation with midazolam in flexible bronchoscopy: a prospective study.
AB  - INTRODUCTION: Sedatives have been increasingly used to improve patient comfort
      during flexible bronchoscopy (FOB). Due to its rapid-onset, anxiolytic and
      amnestic properties, midazolam is one of the most commonly used sedatives.
      OBJECTIVES: To evaluate the effect of sedation with midazolam, including patient
      tolerance, complications and its potential use on a daily routine basis. MATERIAL
      AND METHODS: A multi-centre, prospective, randomized, placebo-controlled study
      was made on 100 patients submitted to FOB in two Pulmonology Departments.
      Midazolam (0.05mg/kg) was administered to patients in Group 1 and saline solution
      (0,9% NaCl) to patients in Group 2, five minutes before the procedure. The
      Hospital Anxiety and Depression Scale (HADS-A) was used to determine patient
      anxiety level. Subjective questionnaires concerning main fears and complaints
      were answered before and after FOB. RESULTS: Mean age was 56.0 +/- 14.1 years;
      66% male. Most (65%) patients had low score (<7) in HADS-A scale with no
      difference between groups. No significant differences were seen between groups
      concerning FOB duration, procedures, lidocaine dosage and complications. Systolic
      blood pressure during and after FOB was significantly higher (p<0.003) in Group
      2. Patients in Group 1 experienced less cough (32% vs 56%; p=0.03) and dyspnea
      (2% vs 34%; p<0.001) than in Group 2, while nausea (6% vs 18%; p>0.05) and pain
      (4% vs 12%; p>0.05) were not statistically different. Willingness to repeat the
      exam was reported in all patients in Group 1 and in 82% in Group 2 (p=0.003).
      CONCLUSION: Sedation with midazolam in FOB improved patient's comfort and
      decreased complaints, without significant haemodynamic changes. It should be
      offered to the patient on a routine basis.

PMID- 22592215
TI  - Abl kinase constructs expressed in bacteria: facilitation of structural and
      functional studies including segmental labeling by expressed protein ligation.
AB  - A great portion of tyrosine kinases are involved in cell development and their
      structural alteration is intimately involved in associated pathologies of
      development and oncology. These kinases are one of the major groups of targets
      under investigation for molecular therapeutics. To carry out biochemical and
      structural biological studies on these kinases, economical production of their
      purified forms is highly desirable. However over-expressing tyrosine kinases as
      recombinant forms in bacterial systems and their purification is a significant
      challenge. Abelson kinase (Abl) has previously been expressed on a large scale to
      facilitate X-ray crystallography and NMR structure studies mainly in baculovirus
      infected insect cells. Even though success has been achieved in expression of
      soluble tyrosine kinases in E. coli with chaperones to improve correct folding,
      low expression levels of kinases are intrinsic in such systems because of
      diversion of resources to produce chaperones. Here we present a straightforward
      method to express and purify isolated Abl kinase domain and SH3-SH2-kinase multi
      domain structures. The expressed Abl protein retains its correct folding and
      biological function. The yield of soluble protein is in a several mg L(-1) range
      in minimal media. Furthermore we demonstrate that segmental isotopic labelling
      using expressed protein ligation can be achieved using bacterial expressed Abl
      kinase domain constructs, which is especially useful in NMR structure-activity
      studies.

PMID- 22592216
TI  - Ovine herpesvirus 2 infection in American bison: virus and host dynamics in the
      development of sheep-associated malignant catarrhal fever.
AB  - Ovine herpesvirus 2 (OvHV-2) is a gammaherpesvirus that causes sheep-associated
      malignant catarrhal fever (SA-MCF), a frequently fatal disease mainly of
      ruminants. This study was designed to define virus-host dynamics following
      experimental OvHV-2 infection in bison. A transient peak in viral DNA accompanied
      by the presence of OvHV-2 ORF25, ORF50 and ORF73 transcripts was observed in
      lungs only from 9 to 12 days post-inoculation (DPI), suggesting occurrence of
      viral replication. This initial viral replication was associated with only a
      subtle increase in transcription of inflammation related genes in lungs and
      tracheal bronchial lymph nodes, while the level of expression of the majority of
      immune genes measured remained comparable to uninfected animals. Increasing viral
      load was observed in the blood and peripheral tissues at 16 and 21 DPI,
      respectively, indicating systemic viral dissemination. Clinical signs of MCF were
      observed between 28 and 35 DPI and the severity of lesions increased as disease
      progressed. Lesion scores were positively correlated with expression levels of
      ORF25, suggesting a contribution of viral replication in the pathogenesis of SA
      MCF. Viral transcripts were observed in all tissues examined from 23 DPI to the
      end of the experiment at 35 DPI and expression levels of ORF25 were significantly
      higher in clinically infected animals as compared to pre-clinical stage. The data
      from this study provide a predictable viral-host interaction time course to test
      hypotheses concerning disease pathogenesis as well as mitigation of SA-MCF in
      susceptible species.

PMID- 22592217
TI  - Porcine reproductive and respiratory syndrome virus activates the transcription
      of interferon alpha/beta (IFN-alpha/beta) in monocyte-derived dendritic cells (Mo
      DC).
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is known to be a poor
      inducer of interferon alpha/beta (IFN-alpha/beta), which may contribute to the
      delayed development of adaptive immunity and the resultant viral persistence.
      However, the exact mechanism by which PRRSV inhibits the induction of IFN
      alpha/beta during infection of its natural host cells remains less well defined.
      Here, we show that PRRSV efficiently activates the transcription of IFN
      alpha/beta in porcine monocyte-derived dendritic cells (Mo-DC) in a time
      dependent and transient manner; and this effect is dependent on the activation of
      phosphatidylinositol 3-kinase (PI3K). Despite the abundant IFN-alpha transcripts
      detected in PRRSV-infected Mo-DC, little or no detectable IFN-alpha is found in
      the supernatants and cell lysates of PRRSV-infected Mo-DC, suggesting that PRRSV
      either blocks the translation of IFN-alpha or inhibits the RNA processing and
      transport. Furthermore, we observed that PRRSV infection significantly reduced
      the induction of IFN-alpha by Poly I:C treatment; and virus replication is
      essential to the effect since heat-inactivated PRRSV has no effect on IFN-alpha
      induction by Poly I:C. Overall, our data provide evidence for the possible role
      of PI3K in the activation of the transcription of IFN-alpha/beta by PRRSV. We
      conclude that PRRSV inhibits the induction of IFN-alpha in Mo-DC by as yet
      undefined post-transcriptional mechanisms.

PMID- 22592259
TI  - Precise X-ray and video overlay for augmented reality fluoroscopy.
AB  - PURPOSE: The camera-augmented mobile C-arm (CamC) augments any mobile C-arm by a
      video camera and mirror construction and provides a co-registration of X-ray with
      video images. The accurate overlay between these images is crucial to high
      quality surgical outcomes. In this work, we propose a practical solution that
      improves the overlay accuracy for any C-arm orientation by: (i) improving the
      existing CamC calibration, (ii) removing distortion effects, and (iii) accounting
      for the mechanical sagging of the C-arm gantry due to gravity. METHODS: A planar
      phantom is constructed and placed at different distances to the image intensifier
      in order to obtain the optimal homography that co-registers X-ray and video with
      a minimum error. To alleviate distortion, both X-ray calibration based on
      equidistant grid model and Zhang's camera calibration method are implemented for
      distortion correction. Lastly, the virtual detector plane (VDP) method is adapted
      and integrated to reduce errors due to the mechanical sagging of the C-arm
      gantry. RESULTS: The overlay errors are 0.38+/-0.06 mm when not correcting for
      distortion, 0.27+/-0.06 mm when applying Zhang's camera calibration, and 0.27+/
      0.05 mm when applying X-ray calibration. Lastly, when taking into account all
      angular and orbital rotations of the C-arm, as well as correcting for distortion,
      the overlay errors are 0.53+/-0.24 mm using VDP and 1.67+/-1.25 mm excluding VDP.
      CONCLUSION: The augmented reality fluoroscope achieves an accurate video and X
      ray overlay when applying the optimal homography calculated from distortion
      correction using X-ray calibration together with the VDP.

PMID- 22592260
TI  - Nuclear localization of actin requires AC102 in Autographa californica multiple
      nucleopolyhedrovirus-infected cells.
AB  - Autographa californica multiple nucleopolyhedrovirus requires nuclear actin for
      progeny virus production and thereby encodes viral products that ensure actin's
      translocation to and retention within the nucleus. Current evidence suggests that
      the ie0-ie1 gene complex along with five nuclear localization of actin (NLA)
      genes are sufficient for NLA in transient transfection experiments. Here we
      report that, during infection, only one of the five NLA genes, Ac102, was
      essential for NLA, and that AC102 had at least one other activity critical for
      budded virus (BV) production. Viral deletion mutants in the other four NLA genes
      were viable, with only two having replication phenotypes different from that of
      the wild type. Infection with AcDeltape38 revealed a delay in both BV production
      and NLA. Infection with AcDelta152 revealed a delay in BV production, but no
      corresponding delay in NLA. Infection with either AcDeltape38 or AcDelta152
      resulted in slightly reduced BV titres. Deletion of Ac004 or he65 had no impact
      on actin translocation kinetics, timing of BV production or BV titres. These
      results implicate AC102 as a key player in baculovirus manipulation of actin.

PMID- 22592262
TI  - Inhibition of integrin alpha6 expression by cell-free varicella-zoster virus.
AB  - Varicella-zoster virus (VZV) causes chickenpox and shingles. VZV is released from
      infected cells during natural infection, but remains highly cell-associated
      during experimental infection, and so most studies have utilized cell-associated
      infection models. We examined the impact of cell-free VZV infection of primary
      human foreskin fibroblasts (HFFs) on the receptor integrin alpha6 (ITGA6). qPCR
      and flow cytometry demonstrated that both cell-free VZV and cell-free UV
      inactivated VZV downregulated transcription and cell-surface protein expression
      of ITGA6. To establish whether ITGA6 altered VZV infection, VZV transcripts and
      nuclear DNA levels were measured in HFFs treated with ITGA6 blocking antibody
      before infection. ITGA6 blocking did not impair virus entry but did negatively
      impact VZV transcription, and this effect was virus specific as transcription of
      the related herpes simplex virus type 1 was not similarly inhibited. This study
      identifies modulation of ITGA6 during cell-free VZV infection, and provides the
      first evidence linking ITGA6 with post-entry productive VZV gene expression.

PMID- 22592261
TI  - Low-pathogenic avian influenza virus A/turkey/Ontario/6213/1966 (H5N1) is the
      progenitor of highly pathogenic A/turkey/Ontario/7732/1966 (H5N9).
AB  - The first confirmed outbreak of highly pathogenic avian influenza (HPAI) virus
      infections in North America was caused by A/turkey/Ontario/7732/1966 (H5N9);
      however, the phylogeny of this virus is largely unknown. This study performed
      genomic sequence analysis of 11 avian influenza isolates from 1956 to 1979 for
      comparison with A/turkey/Ontario/7732/1966 (H5N9). Phylogenetic and genetic
      analyses included these viruses in combination with all known full-genome
      sequences of avian viruses isolated before 1981. It was shown that a low
      pathogenic avian influenza virus, A/turkey/Ontario/6213/1966 (H5N1), that had
      been isolated 3 months previously, was the closest known genetic relative with
      six genome segments of common lineage encoding the polymerase subunits PB2, PB1
      and PA, nucleoprotein (NP), haemagglutinin (HA) and non-structural (NS) proteins.
      The lineages of these genome segments included reassortment with other North
      American turkey viruses that were all rooted in North American wild waterfowl
      with the HA gene originating from the H5N2 serotype. The phylogenies demonstrated
      adaptation from North American wild birds to turkeys with the possible
      involvement of domestic waterfowl. The turkey isolate, A/turkey/Wisconsin/1968
      (H5N9), was the second most closely related poultry isolate to
      A/turkey/Ontario/7732/1966 (H5N9), possessing five common lineage genome segments
      (PB2, PB1, PA, HA and neuraminidase). The A/turkey/Ontario/6213/1966 (H5N1) virus
      was more virulent than A/turkey/Wisconsin/68 (H5N9) for chicken embryos and mice,
      indicating a greater biological similarity to A/turkey/Ontario/7732/1966 (H5N9).
      Thus, A/turkey/Ontario/6213/1966 (H5N1) was identified as the closest known
      ancestral relative of HPAI A/turkey/Ontario/7732/1966 (H5N9), which will serve as
      a useful reference virus for characterizing the early genetic and biological
      properties associated with the emergence of pathogenic avian influenza strains.

PMID- 22592263
TI  - Deep sequencing reveals persistence of intra- and inter-host genetic diversity in
      natural and greenhouse populations of zucchini yellow mosaic virus.
AB  - The genetic diversity present in populations of RNA viruses is likely to be
      strongly modulated by aspects of their life history, including mode of
      transmission. However, how transmission mode shapes patterns of intra- and inter
      host genetic diversity, particularly when acting in combination with de novo
      mutation, population bottlenecks and the selection of advantageous mutations, is
      poorly understood. To address these issues, this study performed ultradeep
      sequencing of zucchini yellow mosaic virus in a wild gourd, Cucurbita pepo ssp.
      texana, under two infection conditions: aphid vectored and mechanically
      inoculated, achieving a mean coverage of approximately 10 ,000*. It was shown
      that mutations persisted during inter-host transmission events in both the aphid
      vectored and mechanically inoculated populations, suggesting that the vector
      imposed transmission bottleneck is not as extreme as previously supposed.
      Similarly, mutations were found to persist within individual hosts, arguing
      against strong systemic bottlenecks. Strikingly, mutations were seen to go to
      fixation in the aphid-vectored plants, suggestive of a major fitness advantage,
      but remained at low frequency in the mechanically inoculated plants. Overall,
      this study highlights the utility of ultradeep sequencing in providing high
      resolution data capable of revealing the nature of virus evolution, particularly
      as the full spectrum of genetic diversity within a population may not be
      uncovered without sequence coverage of at least 2500-fold.

PMID- 22592264
TI  - Two suppressors of RNA silencing encoded by cereal-infecting members of the
      family Luteoviridae.
AB  - Several members of the family Luteoviridae are important pathogens of cultivated
      plant species of the family Gramineae. In this study, we explored RNA-silencing
      suppressors (RSSs) encoded by two cereal-infecting luteoviruses: barley yellow
      dwarf virus and wheat yellow dwarf virus (BYDV and WYDV, respectively). The P0
      protein of WYDV-GPV (P0(GPV)) and the P6 protein of BYDV-GAV (P6(GAV)) displayed
      RSS activities when expressed in agro-infiltrated leaves of Nicotiana
      benthamiana, by their local ability to inhibit post-transcriptional gene
      silencing of GFP. Analysis of GFP, mRNA and GFP-specific small interfering RNA
      indicated that both P0(GPV) and P6(GAV) are suppressors of silencing that can
      restrain not only local but also systemic gene silencing. This is the first
      report of RSS activity of the P6 protein in a member of the genus Luteovirus.

PMID- 22592265
TI  - Whole-genomic analysis of a human G1P[9] rotavirus strain reveals intergenogroup
      reassortment events.
AB  - Group A rotavirus (RVA) strain K8 (RVA/Human-tc/JPN/K8/1977/G1P[9]) was found to
      have Wa-like VP7 and NSP1 genes and AU-1-like VP4 and NSP5 genes. To determine
      the exact origin and overall genetic makeup of this unusual RVA strain, the
      remaining genes (VP1-VP3, VP6 and NSP2-NSP4) of K8 were analysed in this study.
      Strain K8 exhibited a G1-P[9]-I1-R3-C3-M3-A1-N1-T3-E3-H3 genotype constellation,
      not reported previously. The VP6 and NSP2 genes of strain K8 were related closely
      to those of common human Wa-like G1P[8] and/or G3P[8] strains, whilst its VP1
      VP3, NSP3 and NSP4 genes were related more closely to those of AU-1-like RVAs
      and/or AU-1-like genes of multi-reassortant strains than to those of other RVAs.
      Therefore, strain K8 might have originated from intergenogroup-reassortment
      events involving acquisition of four Wa-like genes, possibly from G1P[8] RVAs, by
      an AU-1-like P[9] strain. Whole-genomic analysis of strain K8 has provided
      important insights into the complex genetic diversity of RVAs.

PMID- 22592266
TI  - Limited effect on NS3-NS4A protein cleavage after alanine substitutions within
      the immunodominant HLA-A2-restricted epitope of the hepatitis C virus genotype 3a
      non-structural 3/4A protease.
AB  - It has been well established that immunological escape mutations within the
      hepatitis C virus genotype (gt) 1a non-structural (NS) 3/4A protease are partly
      prevented by a reduction in viral protease fitness. Surprisingly little is known
      about whether similar mutations affect proteases from other genotypes. In the
      present study, we assessed both the HLA-A2-restricted CTL response and gt3a
      NS3/4A protease fitness. Similar to gt1, the 1073-1081 epitope was immunodominant
      within the gt3a-specific HLA-A2-restricted CTL response, despite sequence
      similarity of only 56 % between the gt1a and gt3a genes. However, unlike the gt1a
      NS3/4A protease, all residues within the gt3a 1073-1081 epitope could be replaced
      sequentially by alanine while retaining protease activity, at least in part.

PMID- 22592267
TI  - Three-dimensional structure of the Epstein-Barr virus capsid.
AB  - Epstein-Barr virus (EBV), a gammaherpesvirus, infects >90 % of the world's
      population. Primary infection by EBV can lead to infectious mononucleosis, and
      EBV persistence is associated with several malignancies. Despite its importance
      for human health, little structural information is available on EBV. Here we
      report the purification of the EBV capsid by CsCl- or sucrose density-gradient
      centrifugation. Cryo-electron microscopy and image analysis resulted in two
      slightly different three-dimensional structures at about 20 A resolution. These
      structures were compared with that of human herpesvirus 8, another
      gammaherpesvirus. CsCl-gradient purification leads to the removal of part of the
      triplex complex around the fivefold axes, whereas the complexes between hexons
      remained in place. This may be due to local differences in stability resulting
      from variation in quasi-equivalent interactions between pentons and hexons
      compared with those between hexons only.

PMID- 22592268
TI  - 1D graphene-like silicon systems: silicene nano-ribbons.
AB  - Through this review we can follow the various phases that have led to the
      discovery of the new allotrope form of silicon: silicene. This is a one-atom
      thick silicon sheet arranged in a honeycomb lattice, similar to graphene. For
      silicon, which usually is sp3 hybridized, it represents an unusual and rare
      structure. First, silicene was theoretically hypothesized and subsequently its
      structure calculated as a possible candidate for nano-ribbons of Si grown on the
      anisotropic Ag(110) surface. It was only later, when the physical and chemical
      properties of this peculiar form of silicon, demonstrating the presence of pi and
      pi* bands giving the so-called Dirac cones at the K corners of the Brillouin
      zone, the sp2-like nature of the valence orbitals of the Si-Si bonds and its
      strong resistance towards oxygen were reported, that the real existence of
      silicene became recognized in the scientific community. This review is
      essentially focused on the experimental work performed on 1D isolated silicene
      nano-ribbons and their 1D dense array grown on Ag(110) surfaces.

PMID- 22592269
TI  - A new trend in the experimental methodology for the analysis of the thioflavin T
      binding to amyloid fibrils.
AB  - The studies on the determination of the characteristics of the amyloid fibril
      interaction with the dye were based on the analysis of the dependence of the ThT
      fluorescence intensity on its concentration in the solution containing the
      amyloid fibrils. In the present work, we revealed that this intuitive approach
      provided erroneous data. We propose a new approach which provides a means for
      characterizing the interaction of thioflavin T (ThT) with amyloid fibrils and for
      determining the binding stoichiometry and binding constants, absorption spectrum,
      molar extinction coefficient, and fluorescence quantum yield of the ThT bound to
      the sites of different binding modes of fibrils. The key point of this approach
      is sample preparation by equilibrium microdialysis. The efficiency of the
      proposed approach is demonstrated via the examination of the ThT binding to
      insulin and Abeta42 fibrils as well as to the native form of the Electrophorus
      electricus acetylcholinesterase. We show that the peculiarities of ThT
      interaction with amyloid fibrils depend on the amyloidogenic protein and on the
      binding mode. This approach is universal and can be used for the analysis of
      binding mechanism of any dye that interacts with its receptor. Therefore, the
      proposed approach represents an important addition to the existing arsenal of
      means for the diagnostics and therapy of the neurodegenerative diseases.

PMID- 22592271
TI  - Investigation of viral hepatitis infections possibly associated with health-care
      delivery--New York City, 2008-2011.
AB  - Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are important
      causes of morbidity and mortality in the United States. Because HBV and HCV are
      transmitted efficiently percutaneously, possible transmission in health-care
      settings is of particular concern. Public health investigations of cases of HBV
      and HCV infection suspected to be associated with health-care delivery play an
      essential role in identifying unsafe practices and controlling health-care
      associated viral hepatitis transmission. However, these investigations are
      resource intensive, and frequently overwhelm health department resources. Over
      many years, the New York City Department of Health and Mental Hygiene (DOHMH)
      developed a systematic approach to guide investigation and public health response
      to case reports of acute HBV or HCV infection in patients whose infection was
      potentially associated with health-care delivery. In this approach, the least
      resource-intensive investigation components are conducted for each case, and
      decisions to expand the investigation to more resource-intensive components are
      guided by the likelihood that a single case report represents a cluster of health
      care-associated infections (HAIs). This report describes the DOHMH approach in
      the context of two single case reports. Components of this approach might be
      useful to other health departments that are developing their own approaches to
      this type of investigation.

PMID- 22592270
TI  - 3'poly-G-tailed ODNs inhibit F-spondin to induce cell death and neurite
      retraction in rat embryonic neurons.
AB  - The effects and mechanism of action of oligodeoxyribonucleotides containing CpG
      motif (CpG-ODNs) on neuron cells are largely unexamined. Here, we found that CpG
      A ODNs but not other types of CpG-ODNs induced neurite retraction and cell
      apoptosis of rat embryonic neurons in a TLR9-independent manner. These effects of
      CpG-A ODNs were primarily due to the poly-guanosine at the 3' terminus (3'G
      ODNs). Pull-down analysis showed that 3'G-ODNs associated with transcription
      factor Y-BOX1 (YB-1) to facilitate the translocation of YB-1 into the nucleus via
      the nuclear localizing sequence of YB-1. YB-1 then interacted with the promoter
      of F-spondin directly at -45 and -1,375 sites as demonstrated by chromatin
      immunoprecipitation (ChIP) analysis. Binding of YB-1 to F-spondin promoter
      resulted in downregulation of F-spondin expression. Overexpression of F-spondin
      rescued the cell death and neurite retraction induced by 3'G-ODNs in embryonic
      neuron cells. Taken together, these findings suggest that 3'G-ODNs enhance
      nucleus YB-1 to inhibit F-spondin leading to cell death and neurite retraction of
      embryonic neuron cells.

PMID- 22592272
TI  - Multiple outbreaks of hepatitis B virus infection related to assisted monitoring
      of blood glucose among residents of assisted living facilities--Virginia, 2009
      2011.
AB  - Between February 2009 and November 2011, the Virginia Department of Health (VDH)
      was notified of acute hepatitis B virus (HBV) infections occurring in residents
      of four separate assisted living facilities (ALFs) in the Central Health Planning
      Region of Virginia. In each outbreak, the initial acute HBV infections were
      identified through routine viral hepatitis surveillance. VDH conducted
      epidemiologic and laboratory investigations of these reports. Infection control
      practices, particularly surrounding assisted monitoring of blood glucose (AMBG),
      were assessed by direct observation and staff member interviews. Further
      investigation and subsequent screening of ALF residents for hepatitis B uncovered
      additional acute HBV infections at each of the ALFs. ALF residents screened for
      HBV infection were categorized on the basis of published criteria as having acute
      or chronic infection, or being susceptible or immune to infection. All acute HBV
      infections were among residents receiving AMBG for management of diabetes. AMBG
      is safe when properly performed, but lapses in infection prevention practices
      during AMBG were identified at three of the four facilities. These outbreaks
      highlight the role of hepatitis B surveillance in detecting disease outbreaks and
      the need for a comprehensive strategy to prevent HBV transmission in ALFs,
      including vaccination, improved infection control oversight at ALFs, appropriate
      training of staff members performing AMBG, and prompt investigation of acute HBV
      infections.

PMID- 22592273
TI  - Drowning--United States, 2005-2009.
AB  - Drowning is a leading cause of unintentional injury death worldwide, and the
      highest rates are among children. Overall, drowning death rates in the United
      States have declined in the last decade; however, drowning is the leading cause
      of injury death among children aged 1-4 years. In 2001, approximately 3,300
      persons died from unintentional drowning in recreational water settings, and an
      estimated 5,600 were treated in emergency departments (EDs). To update
      information on the incidence and characteristics of fatal and nonfatal
      unintentional drowning in the United States, CDC analyzed death certificate data
      from the National Vital Statistics System and injury data from the National
      Electronic Injury Surveillance System--All Injury Program (NEISS-AIP) for 2005
      2009. The results indicated that each year an average of 3,880 persons were
      victims of fatal drowning and an estimated 5,789 persons were treated in U.S.
      hospital EDs for nonfatal drowning. Death rates and nonfatal injury rates were
      highest among children aged <=4 years; these children most commonly drowned in
      swimming pools. The drowning death rate among males (2.07 per 100,000 population)
      was approximately four times that for females (0.54). To prevent drowning, all
      parents and children should learn survival swimming skills. In addition, 1)
      environmental protections (e.g., isolation pool fences and lifeguards) should be
      in place; 2) alcohol use should be avoided while swimming, boating, water skiing,
      or supervising children; 3) lifejackets should be used by all boaters and weaker
      swimmers; and 4) all caregivers and supervisors should have training in
      cardiopulmonary resuscitation.

PMID- 22592274
TI  - Promotion of healthy swimming after a statewide outbreak of cryptosporidiosis
      associated with recreational water venues--Utah, 2008-2009.
AB  - During the summer of 2007, Utah experienced a statewide outbreak of
      gastrointestinal illness caused by Cryptosporidium, a parasite transmitted via
      the fecal-oral route. Approximately 5,700 outbreak-related cases were identified
      across the state. Of 1,506 interviewed patients with laboratory-confirmed
      cryptosporidiosis, 1,209 (80%) reported swimming in at least one of approximately
      450 recreational water venues during their potential 14-day incubation period.
      Cryptosporidium is extremely chlorine-tolerant, and secondary or supplemental
      disinfection with ultraviolet light or ozone can control but not prevent
      outbreaks. Because swimmers are the primary source of Cryptosporidium
      contamination, healthy swimming campaigns are needed to increase awareness and
      practice of healthy swimming behaviors, especially not swimming while ill with
      diarrhea (i.e., swimming while ill with diarrhea can lead to gross contamination
      of recreational water). Before the 2008 summer swimming season, Utah public
      health agencies launched a multimedia healthy swimming campaign. To assess
      knowledge of healthy swimming, a survey of Utah residents was conducted during
      July-September 2008. The results of that survey found that 96.1% of respondents
      correctly indicated that "it is not OK to swim if you have diarrhea." In a
      separate national survey in 2009, 100% of Utah residents but only 78.4% of
      residents of other states correctly indicated that "not swimming while ill with
      diarrhea protects others from recreational water illnesses (RWIs)." No
      recreational water-associated outbreaks were detected in Utah during 2008-2011.
      The healthy swimming campaign, as part of a multipronged prevention effort, might
      have helped prevent recreational water-associated outbreaks of cryptosporidiosis
      in Utah.

PMID- 22592275
TI  - Progress toward interruption of wild poliovirus transmission--worldwide, January
      2011-March 2012.
AB  - In January 2012, completion of polio eradication was declared a programmatic
      emergency for global public health by the Executive Board of the World Health
      Organization (WHO). Despite major progress since the launch of the Global Polio
      Eradication Initiative (GPEI) in 1988, circulation of indigenous wild poliovirus
      (WPV) continues in three countries (Afghanistan, Nigeria, and Pakistan). India
      has not reported a polio case since January 2011, and is considered polio-free
      since February 2012. This report highlights progress toward global polio
      eradication during January 2011-March 2012. The number of polio cases reported
      globally decreased by 52%, from 1,352 in 2010 to 650 in 2011. Those 650 cases
      included 341 (53%) reported from the four polio-endemic countries (Afghanistan,
      India, Nigeria, and Pakistan), 230 (35%) from previously polio-free countries in
      which WPV importations led to reestablished transmission for >=12 months (Angola,
      Chad, and Democratic Republic of the Congo [DRC]), and 79 (12%) from nine
      countries affected by outbreaks. Compared with 2010, WPV cases increased in 2011
      in Afghanistan (69%), Nigeria (66%), and Pakistan (27%), but decreased in India
      (98%). During January-March 2012, 59% fewer cases were reported worldwide (as of
      May 15) compared with the same period in 2011, and all cases in 2012 have been
      reported from Afghanistan, Chad, Nigeria, and Pakistan. Although progress toward
      polio eradication was substantial in 2011, persistent WPV circulation in 2012,
      particularly in Nigeria and Pakistan, poses an ongoing threat to eradication
      efforts, underscoring the need for emergency measures by polio-affected countries
      and those at risk for outbreaks after importation.

PMID- 22592276
TI  - Notes from the field : hepatitis C virus infections among young adults--rural
      Wisconsin, 2010.
AB  - During November 2010, Wisconsin Division of Public Health (DPH) staff members
      noted the number of hepatitis C virus (HCV) infections reported annually among
      persons aged <30 years in six contiguous rural counties of Wisconsin had
      increased from an average of eight cases per year during 2004-2008 to an average
      of 24 cases per year during 2009-2010. To understand factors associated with this
      increase, DPH, local health departments, and CDC investigated the epidemiologic
      and laboratory characteristics of 25 cases reported during 2010 among adults aged
      <30 years who resided in these six counties.

PMID- 22592277
TI  - Oxygen cost of breathing and breathlessness during exercise in nonobese women and
      men.
AB  - INTRODUCTION: Although it has been reported that the work of breathing may be
      higher in women, inconsistencies among studies leaves this important question
      unresolved. Also, the association between the oxygen cost of breathing and rating
      of perceived breathlessness (RPB) during exercise has not been examined between
      women and men. PURPOSE: This study aimed to measure oxygen cost of breathing
      during eucapnic voluntary hyperpnea and RPB (Borg 0-10 scale) during 6 min of
      constant work rate cycling at 60 and 90 W, respectively, in healthy, nonobese
      women and men. METHODS: A total of 9 women (27 yr, body mass index = 21 kg.m(-2))
      and 10 men (29 yr, body mass index = 25 kg.m(-2)) participated. All subjects
      underwent pulmonary function testing, exercise cycling, and determination of
      oxygen cost of breathing during eucapnic voluntary hyperpnea. Oxygen cost of
      breathing was obtained from the slope of the oxygen uptake (mL.min(-1)) and
      ventilation (L.min(-1)) relationship. RPB and cardiorespiratory measures were
      collected during minute 6 of the exercise. Data were analyzed by independent t
      test and regression analysis. RESULTS: Age and pulmonary function were similar
      between the nonobese women and men. Oxygen cost of breathing was similar between
      the nonobese women (1.17 +/- 0.26 mL.L(-1)) and men (1.21 +/- 0.42 mL.(-1)L). RPB
      during exercise was similar between the women (2.1 +/- 1.3) and men (2.6 +/- 1.2)
      and was correlated (P < 0.05) with relative oxygen uptake (r = 0.55) but not the
      oxygen cost of breathing. CONCLUSIONS: In nonobese women and men, oxygen cost of
      breathing is not different over the ventilatory ranges studied and RPB is similar
      at the same relative exercise intensity. In addition, the oxygen cost of
      breathing was not associated with RPB during constant work rate exercise.

PMID- 22592278
TI  - Real-time head acceleration measurement in girls' youth soccer.
AB  - PURPOSE: The purpose of the current study was to collect real-time head
      acceleration data for soccer impacts during girls' youth (U14) soccer play.
      METHODS: Linear and angular head accelerations were collected during girls' youth
      soccer scrimmages using a wireless head acceleration measurement device (the Head
      Impact Telemetry System). After field data collection, each individual impact was
      analyzed. The type of impact, header or nonheader, was determined, and nonheader
      impacts were further assessed by the category of impact. The head injury
      criterion and resultant linear and angular accelerations were analyzed and
      compared with current injury tolerance values for all impacts. RESULTS: A total
      of 47 header and 20 nonheader impacts were observed during the study. The front
      of the head experienced more headers than the other locations (n = 17). Header
      impacts ranged in peak linear acceleration from 4.5 g to 62.9 g and in peak
      angular head acceleration from 444.8 to 8869.1 rad.s(-2). The majority of the
      nonheader impacts (40%) were player collisions with other players. Only one
      goalpost collision occurred, but it resulted in the highest peak angular
      acceleration (5179.5 rad.s(-2)) and was the only nonheader impact to exceed any
      of the tolerance levels. CONCLUSIONS: Head accelerations were found to exceed the
      majority of previous laboratory studies. None of the impacts exceeded linear
      acceleration tolerance values for concussion, but angular accelerations did
      exceed the suggested limits. Three angular acceleration measurements for heading
      events (4509.8, 5298.3, and 8869.1 rad.s(-2)) exceeded the concussion tolerance
      values, but no concussions were diagnosed during the study.

PMID- 22592279
TI  - Dysanapsis:  importance of measured lung static recoil pressure.

PMID- 22592283
TI  - A framework to prevent and control tobacco among adolescents and children:
      introducing the IMPACT model.
AB  - The objective of this paper is to provide a comprehensive evidence based model
      aimed at addressing multi-level risk factors influencing tobacco use among
      children and adolescents with multi-level policy and programmatic approaches in
      India. Evidences around effectiveness of policy and program interventions from
      developed and developing countries were reviewed using Pubmed, Scopus, Google
      Scholar and Ovid databases. This evidence was then categorized under three broad
      approaches: Policy level approaches (increased taxation on tobacco products,
      smoke-free laws in public places and work places, effective health warnings,
      prohibiting tobacco advertising, promotions and sponsorships, and restricting
      access to minors); Community level approaches (school health programs, mass media
      campaigns, community based interventions, promoting tobacco free norms) and
      Individual level approaches (promoting cessation in various settings). This
      review of literature around determinants and interventions was organized into
      developing the IMPACT framework. The paper further presents a comparative
      analysis of tobacco control interventions in India vis a vis the proposed
      approaches. Mixed results were found for prevention and control efforts targeting
      youth. However, this article suggests a number of intervention strategies that
      have shown to be effective. Implementing these interventions in a coordinated way
      will provide potential synergies across interventions. Pediatricians have
      prominent role in advocating and implementing the IMPACT framework in countries
      aiming to prevent and control tobacco use among adolescents and children.

PMID- 22592284
TI  - Atypical Kawasaki disease.

PMID- 22592285
TI  - MR volumetric changes after diagnostic CSF removal in normal pressure
      hydrocephalus.
AB  - Although diagnostic CSF removal in patients with suspected normal pressure
      hydrocephalus (NPH) is performed frequently, its impact on changes of the global
      brain volume and volume of the ventricles has not been studied in detail. We
      examined 20 patients with clinical and radiological signs of NPH. These received
      MRI prior to and immediately after diagnostic CSF removal, either via lumbar
      puncture (TAP, n = 10) or via external lumbar drainage (ELD, n = 10). Changes in
      global brain volume were assessed using SIENA, a tool from the FSL software
      library. Additionally, we determined the change of the lateral ventricles' volume
      by manual segmentation. Furthermore, we recorded systematic clinical assessments
      of the key features of NPH. The median volume of CSF removed was 35 ml in TAP
      patients and 406 ml in ELD patients. Changes in global brain volume were found in
      both patient groups. Brain volume change was significantly larger in ELD patients
      than in TAP patients (p = 0.022), and correlated with the volume of CSF removal
      (r = 0.628, p = 0.004). Brain volume expansion was most pronounced adjacent to
      the lateral ventricles, but also detectable in the temporal and frontal regions.
      The median ventricular volume decreased after CSF removal. Ventricular volume
      reduction was more pronounced in ELD patients than in TAP patients. This study
      quantifies for the first time immediate volumetric changes of global brain tissue
      and of ventricles after diagnostic CSF removal in NPH patients. In particular, we
      report evidence that CSF removal results in a change of the brain volume rather
      than only a change of the brain's shape.

PMID- 22592286
TI  - Tremor-spectrum in spinocerebellar ataxia type 3.
AB  - Spinocerebellar ataxia type 3 (SCA3) can be present with a combination of
      cerebellar, neuropathic, pyramidal, or extrapyramidal symptoms. Tremor is a
      classical but not frequent manifestation of SCA3 and there is a lack of detailed
      knowledge regarding its origin. To study the clinical and electrophysiological
      characteristics of tremor in SCA3 patients, the authors conducted a case series
      of 72 SCA3 patients. Clinical characteristics of tremor and associated signs,
      response to treatments, follow-up, and genetic results were collected.
      Electrophysiological study including polymyographic recording was possible in 4/6
      patients and DaTSCAN in 2/6. The authors also performed a systematic review of
      SCA3 cases with tremor (n = 36) reported previously in the literature. We
      identified two different tremor-types in 6/72 patients with SCA3 mutations, a
      "fast" (6.5-8 Hz) action, postural or tremor in orthostatism (initial symptom),
      which became slower over time with associated parkinsonism with a follow-up of 10
      years and a "slow" rest, action and intention tremor (3-4 Hz) with distal and
      proximal component (including axial tremor in orthostatism). Total improvement of
      limbs and tremor in orthostatism was obtained with levodopa with occurrence of
      fluctuations/dyskinesia. Partial benefit was observed when additional signs were
      present (myoclunus/dystonia). The differences in tremor subtypes in SCA3 may be
      related to various combinations of mild to severe dysfunctions of the cerebello
      thalamo-cortical loop and the nigro-striatal dopaminergic pathway.

PMID- 22592287
TI  - Biomarker level improves the diagnosis of embolic source in ischemic stroke of
      unknown origin.
AB  - The risk of recurrent stroke is likely related to etiology. Therefore it is
      important to identify which patients are at highest early risk. We evaluated
      whether selected blood biomarkers may aid in the diagnosis of stroke etiology. We
      studied consecutive non-lacunar stroke patients between November 2006 and January
      2007, and selected undetermined origin strokes. Blood samples were drawn at
      arrival to test brain natriuretic peptide (BNP), D-dimer, CK-MB, myoglobin, and
      troponin. Second harmonic transthoracic echocardiography (SHTTE) and ECG-24 h
      monitoring were also performed within the first 24 h. We evaluated 294 patients
      with ischemic stroke; 89 had an initial undetermined origin. After a
      cardiological work-up, 49 were diagnosed as embolic including atrial fibrillation
      (4), severe aortic arch atheromatosis (24), severe wall abnormalities (12), valve
      disease (3), dilated cardiomyopathy (1), and patent foramen (5). Higher levels of
      CK-MB, BNP, and myoglobin were found in patients with embolic source in SHTTE,
      but only CK-MB >1.5 ng/ml and BNP >64 pg/ml remained as independent predictors:
      BNP (OR 8.86; CI 95 % 2.79-28.09), CK-MB (OR 6.28; CI 95 % 1.66-23.69). BNP
      showed specificity of 75 %, sensitivity of 63.4 %, and positive predictive value
      (PPV) of 75.6 %. CK-MB had specificity of 85 %, sensitivity of 47.9 %, and PPV of
      79.3 %. Measuring both biomarkers improves the finding of embolic source,
      increasing specificity to 95 % and PPV to 88.2 %. High-level CK-MB and BNP during
      the acute phase of ischemic stroke are associated with an embolic source.
      Measurement of both biomarkers may improve the diagnosis, guiding the need to
      perform a heart exploration.

PMID- 22592288
TI  - IVIG treatment in post-polio patients: evaluation of responders.
AB  - The aim of this work is to evaluate the outcome of IVIG treatment in patients
      with post-polio syndrome (PPS) and to identify responders. The study included 113
      PPS patients who had received one IVIG treatment in an open trial, prospective
      follow-up study. Clinical examination was performed and clinical data were
      retrieved from medical records. The short form 36 (SF-36), physical activity
      scale for the elderly (PASE), and the visual analogue scale (VAS) were used as
      measurements of quality of life, physical activity, and the intensity of pain.
      Data before treatment and at 6-month follow-up were collected. Analysis was
      performed in subgroups based on demographic and medical parameters. A
      statistically significant increase of the SF-36 sub domains bodily pain,
      vitality, social function, role emotional, and the mental compound score (MCS)
      was found at the 6-month follow-up. A significant decrease of pain was found in
      patients who reported pain intensity over VAS of 20 mm, in patients younger than
      65 years of age and in patients who had paresis in the lower extremities. A trend
      was found in patients with PPS as the only diagnosis. IVIG leads to increase of
      quality of life at 6-month follow-up for SF-36 regarding sub domains of bodily
      pain, vitality, social function, role emotional, as well as for pain. Age below
      65 years, paresis in the lower extremities, and lack of concomitant disorders may
      be the main indicators for a future identification of responders.

PMID- 22592289
TI  - Imaging characteristics of metastatic chordoma.
AB  - PURPOSE: Our aim was to describe the incidence and sites of metastatic chordomas
      and show their characteristic computed tomography (CT) and magnetic resonance
      (MR) findings. MATERIALS AND METHODS: One hundred ninety-eight chordoma patients
      were registered in the institutional database and were followed up with CT and MR
      examinations for periods ranging from 1 to 158 months. Clinical features and CT
      and MR findings of metastatic chordomas were analyzed by two radiologists.
      RESULTS: We counted 86 metastatic sites in 49 of 198 patients. The incidence of
      metastasis was 24.7 %. Sites of metastases were bone, lung, liver, lymph node,
      muscle, skin, pleura, cerebellum, cardiac muscle, pericardium, and adrenal gland.
      Duration from the diagnosis to the first detection of metastasis ranged from 0 to
      600 months, with an average of 45.0 months. Osteolytic lesions were most common
      bone metastases, but osteosclerotic metastasis was also encountered. Metastatic
      chordoma showed very high intensity on diffusion-weighted (DW) images in 29 of 31
      patients. CONCLUSION: Metastases of chordoma are not rare and may occur several
      years after primary lesion presentation. The high intensity of DW images is
      characteristic and helpful for detecting metastatic chordoma.

PMID- 22592290
TI  - What is the optimal dietary intake of vitamin D for reducing fracture risk?
AB  - Vitamin D has long been known to be important for bone health, but there is
      currently no consensus on the amount of vitamin D needed or how it varies with
      age, race/ethnicity, body size, absorption efficiency, season, and other factors.
      This review describes the effects of vitamin D on calcium absorption, parathyroid
      hormone levels, and changes in bone mineral density briefly and focuses in more
      detail on the results and interpretation of double-blind randomized controlled
      trials with fracture outcomes in older adults. Based on these trials, 400 IU/day,
      bringing 25-hydroxyvitamin D (25OHD) levels to 60-65 nmol/L, is not effective at
      lowering fracture risk in community-dwelling elders or in elders with prior
      fractures. Several large trials indicate that doses in the range of 700-1,000
      IU/day can lower fracture risk by ~20 %. From these trials, it appears that a
      25OHD level of 65 nmol/L is needed to reduce nonvertebral fracture risk and 75
      nmol/L may be needed to lower hip fracture risk. Trials testing additional doses
      of vitamin D in different segments of the population are needed.

PMID- 22592291
TI  - Regional prediction of tissue fate in acute ischemic stroke.
AB  - Early and accurate prediction of tissue outcome is essential to the clinical
      decision-making process in acute ischemic stroke. We present a quantitative
      predictive model of tissue fate that combines regional imaging features available
      after onset. A key component is the use of cuboids randomly sampled during the
      learning process. Models trained with time-to-maximum feature (Tmax) computed
      from perfusion weighted images (PWI) are compared to the ones obtained from the
      apparent diffusion coefficient (ADC). The prediction task is formalized as a
      regression problem where the inputs are the local cuboids extracted from Tmax or
      ADC images at onset, and the output is the segmented FLAIR intensity of the
      tissue 4 days after intervention. Experiments on 25 acute stroke patients
      demonstrate the effectiveness of the proposed approach in predicting tissue fate.
      Results on our dataset show the superiority of the regional model vs. a single
      voxel-based approach, indicate that PWI regional models outperform ADC models,
      and demonstrates that a nonlinear regression model significantly improves the
      results in comparison to a linear model.

PMID- 22592292
TI  - An organometallic approach for ultrathin SnO(x)Fe(y)S(z) plates and their
      graphene composites as stable anode materials for high performance lithium ion
      batteries.
AB  - Through an organometallic approach, ultrathin SnO(x)Fe(y)S(z) plates with ~2 nm
      single layer-thicknesses were obtained and their graphene composites showed very
      promising discharge capacities of up to 736 mA h g(-1) and excellent stabilities
      as anode materials in lithium ion batteries.

PMID- 22592293
TI  - Kinetic arrest of the first-order to R3c Pbnm phase transition in supercooled
      La(x)MnO(3+delta) (x = 1 and 0.9).
AB  - We report the occurrence of kinetic arrest of the first-order phase transition
      from R3c to Pbnm in supercooled La(x)MnO(3+/-delta) (x = 1 and 0.9, i.e. delta >
      0.125). Structural studies have been done, employing low temperature transmission
      electron microscopy (LT-TEM) and low temperature x-ray diffraction (LT-XRD)
      techniques. No phase transformation was observed even in La(x)MnO(3+/-delta) aged
      for ~12 h at 98 K. The evidence of the occurrence of kinetic arrest was realized
      at low temperatures through in situ electron beam triggered nucleation and
      perpetual devitrification of the R3c phase into a Pbnm phase. It was clearly
      evidenced that the R3c structure of La(x)MnO(3+/-delta), below its ferromagnetic
      transition temperature, is metastable and prone to be transformed to a Pbnm
      orthorhombic structure following initiation by an electron beam trigger. The
      electron beam transformed Pbnm phase was found to transform back to the R3c phase
      through a first-order phase transition occurring close to the ferromagnetic to
      paramagnetic transition (T(c)) during heating. The glass-like kinetics of the
      arrested R3c phase has been investigated through resistance relaxation
      measurements, showing a decreasing logarithmic rate of decay of the arrested R3c
      phase towards the stable Pbnm phase with decreasing temperature, down to 5 K. On
      the basis of the correlations observed in the resistance-versus-temperature,
      magnetization-versus-temperature, magnetization-versus-field, resistance
      relaxation and LT-XRD measurements, the occurrence of kinetic arrest has been
      attributed to the suppression of Jahn-Teller distortion by double exchange across
      the insulator-metal transition.

PMID- 22592295
TI  - Galvestine-1, a novel chemical probe for the study of the glycerolipid
      homeostasis system in plant cells.
AB  - Plant cells are characterized by the presence of chloroplasts, membrane lipids of
      which contain up to ~80% mono- and digalactosyldiacylglycerol (MGDG and DGDG).
      The synthesis of MGDG in the chloroplast envelope is essential for the biogenesis
      and function of photosynthetic membranes, is coordinated with lipid metabolism in
      other cell compartments and is regulated in response to environmental factors.
      Phenotypic analyses of Arabidopsis using the recently developed specific
      inhibitor called galvestine-1 complete previous analyses performed using various
      approaches, from enzymology, cell biology to genetics. This review details how
      this probe could be beneficial to study the lipid homeostasis system at the whole
      cell level and highlights connections between MGDG synthesis and Arabidopsis
      flower development.

PMID- 22592296
TI  - Me3SiI-promoted reaction of salicylic aldehydes with ketones: a facile way to
      construct benzopyranic [2,3-b]ketals and spiroketals.
AB  - Me(3)SiI-promoted reaction of salicylic aldehydes with ketones via
      arylmethylation at the alpha-site of the carbonyl group and cyclodehydration of
      keto-diol provided a facile way to construct heteroannular ketals, furnishing
      benzopyranic [2,3-b]ketals and spiroketals in moderate to good yields.

PMID- 22592297
TI  - Psychology in academic health centers: a true healthcare home.
AB  - This article is based on the invited presentation by the author at the American
      Psychological Association's Annual Convention, August 4-7, 2011, upon his receipt
      of the Joseph D. Matarazzo Award for Distinguished Contributions to Psychology in
      Academic Health Centers presented by the Association of Psychologists in Academic
      Health Centers. This article relates the history, roles, and responsibilities of
      psychologists in academic health centers to the ultimate survival and success of
      professional psychology. It describes implications of the Patient Protection and
      Affordable Care Act (ACA) on the institutional practice of psychology including
      how psychology's place in academic health centers positions the field well for
      the future of healthcare reform. The article provides several recommendations to
      help professional psychology prepare for that future of integrated,
      interprofessional healthcare.

PMID- 22592299
TI  - Inflammation: the gut takes a toll on liver cancer.

PMID- 22592300
TI  - Cell cycle: a WEE pointer.

PMID- 22592301
TI  - Multiple myeloma: evolution by alternating dominance.

PMID- 22592302
TI  - Energy margins in dynamic object manipulation.
AB  - Many tasks require humans to manipulate dynamically complex objects and maintain
      appropriate safety margins, such as placing a cup of coffee on a coaster without
      spilling. This study examined how humans learn such safety margins and how they
      are shaped by task constraints and changing variability with improved skill.
      Eighteen subjects used a manipulandum to transport a shallow virtual cup
      containing a ball to a target without losing the ball. Half were to complete the
      cup transit in a comfortable target time of 2 s (a redundant task with infinitely
      many equivalent solutions), and the other half in minimum time (a nonredundant
      task with one explicit cost to optimize). The safety margin was defined as the
      ball energy relative to escape, i.e., as an energy margin. The first hypothesis,
      that subjects converge to a single strategy in the minimum-time task but choose
      different strategies in the less constrained target-time task, was not supported.
      Both groups developed individualized strategies with practice. The second
      hypothesis, that subjects decrease safety margins in the minimum-time task but
      increase them in the target-time task, was supported. The third hypothesis, that
      in both tasks subjects modulate energy margins according to their execution
      variability, was partially supported. In the target-time group, changes in energy
      margins correlated positively with changes in execution variability; in the
      minimum-time group, such a relation was observed only at the end of practice, not
      across practice. These results show that when learning a redundant object
      manipulation task, most subjects increase their safety margins and shape their
      movement strategies in accordance with their changing variability.

PMID- 22592303
TI  - Contribution of the retrotrapezoid nucleus/parafacial respiratory region to the
      expiratory-sympathetic coupling in response to peripheral chemoreflex in rats.
AB  - Central mechanisms of coupling between respiratory and sympathetic systems are
      essential for the entrainment between the enhanced respiratory drive and
      sympathoexcitation in response to hypoxia. However, the brainstem nuclei and
      neuronal network involved in these respiratory-sympathetic interactions remain
      unclear. Here, we evaluated whether the increase in expiratory activity and
      expiratory-modulated sympathoexcitation produced by the peripheral chemoreflex
      activation involves the retrotrapezoid nucleus/parafacial respiratory region
      (RTN/pFRG). Using decerebrated arterially perfused in situ rat preparations (60
      80 g), we recorded the activities of thoracic sympathetic (tSN), phrenic (PN),
      and abdominal nerves (AbN) as well as the extracellular activity of RTN/pFRG
      expiratory neurons, and reflex responses to chemoreflex activation were evaluated
      before and after inactivation of the RTN/pFRG region with muscimol (1 mM). In the
      RTN/pFRG, we identified late-expiratory (late-E) neurons (n = 5) that were silent
      at resting but fired coincidently with the emergence of late-E bursts in AbN
      after peripheral chemoreceptor activation. Bilateral muscimol microinjections
      into the RTN/pFRG region (n = 6) significantly reduced basal PN frequency, mean
      AbN activity, and the amplitude of respiratory modulation of tSN (P < 0.05). With
      respect to peripheral chemoreflex responses, muscimol microinjections in the
      RTN/pFRG enhanced the PN inspiratory response, abolished the evoked late-E
      activity of AbN, but did not alter either the magnitude or pattern of the tSN
      reflex response. These findings indicate that the RTN/pFRG region is critically
      involved in the processing of the active expiratory response but not of the
      expiratory-modulated sympathetic response to peripheral chemoreflex activation of
      rat in situ preparations.

PMID- 22592304
TI  - Adaptation to heading direction dissociates the roles of human MST and V6 in the
      processing of optic flow.
AB  - The extraction of optic flow cues is fundamental for successful locomotion.
      During forward motion, the focus of expansion (FoE), in conjunction with
      knowledge of eye position, indicates the direction in which the individual is
      heading. Therefore, it is expected that cortical brain regions that are involved
      in the estimation of heading will be sensitive to this feature. To characterize
      cortical sensitivity to the location of the FoE or, more generally, the center of
      flow (CoF) during visually simulated self-motion, we carried out a functional MRI
      (fMRI) adaptation experiment in several human visual cortical areas that are
      thought to be sensitive to optic flow parameters, namely, V3A, V6, MT/V5, and
      MST. In each trial, two optic flow patterns were sequentially presented, with the
      CoF located in either the same or different positions. With an adaptation design,
      an area sensitive to heading direction should respond more strongly to a pair of
      stimuli with different CoFs than to stimuli with the same CoF. Our results show
      such release from adaptation in areas MT/V5 and MST, and to a lesser extent V3A,
      suggesting the involvement of these areas in the processing of heading direction.
      The effect could not be explained either by differences in local motion or by
      attention capture. It was not observed to a significant extent in area V6 or in
      control area V1. The different patterns of responses observed in MST and V6,
      areas that are both involved in the processing of egomotion in macaques and
      humans, suggest distinct roles in the processing of visual cues for self-motion.

PMID- 22592305
TI  - Validation of a within-trial measure of the oculomotor stop process.
AB  - The countermanding (or stop signal) task requires subjects try to withhold a
      planned movement upon the infrequent presentation of a stop signal. We have
      previously proposed a within-trial measure of movement cancellation based on neck
      muscle recruitment during the cancellation of eye-head gaze shifts. Here, we
      examined such activity after either a bright or dim stop signal, a manipulation
      known to prolong the stop signal reaction time (SSRT). Regardless of stop signal
      intensity, subjects generated an appreciable number of head-only errors during
      successfully cancelled gaze shifts (compensatory eye-in-head motion ensured gaze
      stability), wherein subtle head motion toward a peripheral target was ultimately
      stopped by a braking pulse of antagonist neck muscle activity. Both the SSRT and
      timing of antagonist muscle recruitment relative to the stop signal increased for
      dim stop signals and decreased for longer stop signal delays. Moreover, we
      observed substantial variation in the distribution of antagonist muscle
      recruitment latencies across our sample. The magnitude and variance of the SSRTs
      and antagonist muscle recruitment latencies correlated positively across
      subjects, as did the within-subject changes across bright and dim stop signals.
      Finally, we fitted our behavioral data with a race model architecture that
      incorporated a lower threshold for initiating head movements. This model allowed
      us to estimate the efferent delay between the completion of a central stop
      process and the recruitment of antagonist neck muscles; the estimated efferent
      delay remained consistent within subjects across stop signal intensity. Overall,
      these results are consistent with the hypothesis that neck muscle recruitment
      during a specific subset of cancelled trials provides a peripheral expression of
      oculomotor cancellation on a single trial. In the discussion, we briefly
      speculate on the potential value of this measure for research in basic or
      clinical domains and consider current issues that limit more widespread use.

PMID- 22592306
TI  - Neural ITD coding with bilateral cochlear implants: effect of binaurally coherent
      jitter.
AB  - Poor sensitivity to the interaural time difference (ITD) constrains the ability
      of human bilateral cochlear implant users to listen in everyday noisy acoustic
      environments. ITD sensitivity to periodic pulse trains degrades sharply with
      increasing pulse rate but can be restored at high pulse rates by jittering the
      interpulse intervals in a binaurally coherent manner (Laback and Majdak. Binaural
      jitter improves interaural time-difference sensitivity of cochlear implantees at
      high pulse rates. Proc Natl Acad Sci USA 105: 814-817, 2008). We investigated the
      neural basis of the jitter effect by recording from single inferior colliculus
      (IC) neurons in bilaterally implanted, anesthetized cats. Neural responses to
      trains of biphasic pulses were measured as a function of pulse rate, jitter, and
      ITD. An effect of jitter on neural responses was most prominent for pulse rates
      above 300 pulses/s. High-rate periodic trains evoked only an onset response in
      most IC neurons, but introducing jitter increased ongoing firing rates in about
      half of these neurons. Neurons that had sustained responses to jittered high-rate
      pulse trains showed ITD tuning comparable with that produced by low-rate periodic
      pulse trains. Thus, jitter appears to improve neural ITD sensitivity by restoring
      sustained firing in many IC neurons. The effect of jitter on IC responses is
      qualitatively consistent with human psychophysics. Action potentials tended to
      occur reproducibly at sparse, preferred times across repeated presentations of
      high-rate jittered pulse trains. Spike triggered averaging of responses to
      jittered pulse trains revealed that firing was triggered by very short interpulse
      intervals. This suggests it may be possible to restore ITD sensitivity to
      periodic carriers by simply inserting short interpulse intervals at select times.

PMID- 22592307
TI  - Methamphetamine produces bidirectional, concentration-dependent effects on
      dopamine neuron excitability and dopamine-mediated synaptic currents.
AB  - Amphetamine-like compounds are commonly used to enhance cognition and to treat
      attention deficit/hyperactivity disorder, but they also function as positive
      reinforcers and are self-administered at doses far exceeding clinical relevance.
      Many of these compounds (including methamphetamine) are substrates for dopamine
      reuptake transporters, elevating extracellular dopamine by inhibiting uptake and
      promoting reverse transport. This produces an increase in extracellular dopamine
      that inhibits dopamine neuron firing through autoreceptor activation and
      consequently blunts phasic dopamine neurotransmission, an important learning
      signal. However, these mechanisms do not explain the beneficial behavioral
      effects observed at clinically useful concentrations. In the present study, we
      have used patch-clamp electrophysiology in slices of mouse midbrain to show that,
      surprisingly, low concentrations of methamphetamine actually enhance dopamine
      neurotransmission and increase dopamine neuron firing through a dopamine
      transporter-mediated excitatory conductance. Both of these effects are reversed
      by higher concentrations of methamphetamine, which inhibit firing through
      dopamine D2 autoreceptor activation and decrease the peak amplitude of dopamine
      mediated synaptic currents. These competing, concentration-dependent effects of
      methamphetamine suggest a mechanistic interplay by which lower concentrations of
      methamphetamine can overcome autoreceptor-mediated inhibition at the soma to
      increase phasic dopamine transmission.

PMID- 22592308
TI  - Frequency-dependent amplification of stretch-evoked excitatory input in spinal
      motoneurons.
AB  - Voltage-dependent calcium and sodium channels mediating persistent inward
      currents (PICs) amplify the effects of synaptic inputs on the membrane potential
      and firing rate of motoneurons. CaPIC channels are thought to be relatively slow,
      whereas the NaPIC channels have fast kinetics. These different characteristics
      influence how synaptic inputs with different frequency content are amplified; the
      slow kinetics of Ca channels suggest that they can only contribute to
      amplification of low frequency inputs (<5 Hz). To characterize frequency
      dependent amplification of excitatory postsynaptic potentials (EPSPs), we
      measured the averaged stretch-evoked EPSPs in cat medial gastrocnemius
      motoneurons in decerebrate cats at different subthreshold levels of membrane
      potential. EPSPs were produced by muscle spindle afferents activated by
      stretching the homonymous and synergist muscles at frequencies of 5-50 Hz. We
      adjusted the stretch amplitudes at different frequencies to produce approximately
      the same peak-to-peak EPSP amplitude and quantified the amount of amplification
      by expressing the EPSP integral at different levels of depolarization as a
      percentage of that measured with the membrane hyperpolarized. Amplification was
      observed at all stretch frequencies but generally decreased with increasing
      stretch frequency. However, in many cells the amount of amplification was greater
      at 10 Hz than at 5 Hz. Fast amplification was generally reduced or absent when
      the lidocaine derivative QX-314 was included in the electrode solution,
      supporting a strong contribution from Na channels. These results suggest that
      NaPICs can combine with CaPICs to enhance motoneuron responses to modulations of
      synaptic drive over a physiologically significant range of frequencies.

PMID- 22592309
TI  - Level dependence of spatial processing in the primate auditory cortex.
AB  - Sound localization in both humans and monkeys is tolerant to changes in sound
      levels. The underlying neural mechanism, however, is not well understood. This
      study reports the level dependence of individual neurons' spatial receptive
      fields (SRFs) in the primary auditory cortex (A1) and the adjacent caudal field
      in awake marmoset monkeys. We found that most neurons' excitatory SRF components
      were spatially confined in response to broadband noise stimuli delivered from the
      upper frontal sound field. Approximately half the recorded neurons exhibited
      little change in spatial tuning width over a ~20-dB change in sound level,
      whereas the remaining neurons showed either expansion or contraction in their
      tuning widths. Increased sound levels did not alter the percent distribution of
      tuning width for neurons collected in either cortical field. The population
      averaged responses remained tuned between 30- and 80-dB sound pressure levels for
      neuronal groups preferring contralateral, midline, and ipsilateral locations. We
      further investigated the spatial extent and level dependence of the suppressive
      component of SRFs using a pair of sequentially presented stimuli. Forward
      suppression was observed when the stimuli were delivered from "far" locations,
      distant to the excitatory center of an SRF. In contrast to spatially confined
      excitation, the strength of suppression typically increased with stimulus level
      at both the excitatory center and far regions of an SRF. These findings indicate
      that although the spatial tuning of individual neurons varied with stimulus
      levels, their ensemble responses were level tolerant. Widespread spatial
      suppression may play an important role in limiting the sizes of SRFs at high
      sound levels in the auditory cortex.

PMID- 22592310
TI  - Limited interlimb transfer of locomotor adaptations to a velocity-dependent force
      field during unipedal walking.
AB  - Several studies have demonstrated that motor adaptations to a novel task
      environment can be transferred between limbs. Such interlimb transfer of motor
      commands is consistent with the notion of centrally driven strategies that can be
      generalized across different frames of reference. So far, studies of interlimb
      transfer of locomotor adaptations have yielded disparate results. Here we sought
      to determine whether locomotor adaptations in one (trained) leg show transfer to
      the other (test) leg during a unipedal walking task. We hypothesized that
      adaptation in the test leg to a velocity-dependent force field previously
      experienced by the trained leg will be faster, as revealed by faster recovery of
      kinematic errors and earlier onset of aftereffects. Twenty able-bodied adults
      walked unipedally in the Lokomat robotic gait orthosis, which applied velocity
      dependent resistance to the legs. The amount of resistance was scaled to 10% of
      each individual's maximum voluntary contraction of the hip flexors.
      Electromyography and kinematics of the lower limb were recorded. All subjects
      were right-leg dominant and were tested for transfer of motor adaptations from
      the right leg to the left leg. Catch trials, consisting of unexpected removal of
      resistance, were presented after the first step with resistance and after a
      period of adaptation to test for aftereffects. We found no significant
      differences in the sizes of the aftereffects between the two legs, except for
      peak hip flexion during swing, or in the rate at which peak hip flexion adapted
      during steps against resistance between the two legs. Our results indicate that
      interlimb transfer of these types of locomotor adaptation is not a robust
      phenomenon. These findings add to our current understanding of motor adaptations
      and provide further evidence that generalization of adaptations may be dependent
      on the movement task.

PMID- 22592311
TI  - Intraglomerular inhibition shapes the strength and temporal structure of
      glomerular output.
AB  - Odor signals are transmitted to the olfactory bulb by olfactory nerve (ON)
      synapses onto mitral/tufted cells (MCs) and external tufted cells (ETCs). ETCs,
      in turn, provide feedforward excitatory input to MCs. MC and ETCs are also
      regulated by inhibition: intraglomerular and interglomerular inhibitory circuits
      act at MC and ETC apical dendrites; granule cells (GCs) inhibit MC lateral
      dendrites via the MC->GC->MC circuit. We investigated the contribution of
      intraglomerular inhibition to MC and ETCs responses to ON input. ON input evokes
      initial excitation followed by early, strongly summating inhibitory postsynaptic
      currents (IPSCs) in MCs; this is followed by prolonged, intermittent IPSCs. The N
      methyl-d-aspartate receptor antagonist dl-amino-5-phosphovaleric acid, known to
      suppress GABA release by GCs, reduced late IPSCs but had no effect on early
      IPSCs. In contrast, selective intraglomerular block of GABA(A) receptors
      eliminated all early IPSCs and caused a 5-fold increase in ON-evoked MC spiking
      and a 10-fold increase in response duration. ETCs also receive intraglomerular
      inhibition; blockade of inhibition doubled ETC spike responses. By reducing ETC
      excitatory drive and directly inhibiting MCs, intraglomerular inhibition is a key
      factor shaping the strength and temporal structure of MC responses to sensory
      input. Sensory input generates an intraglomerular excitation-inhibition sequence
      that limits MC spike output to a brief temporal window. Glomerular circuits may
      dynamically regulate this input-output window to optimize MC encoding across
      sniff-sampled inputs.

PMID- 22592312
TI  - AMPA receptor-dependent, light-evoked D-serine release acts on retinal ganglion
      cell NMDA receptors.
AB  - NMDA receptor (NMDAR) activation requires coincident binding of the excitatory
      neurotransmitter glutamate and a coagonist, either glycine or D-serine. Changes
      in NMDAR currents during neural transmission are typically attributed to
      glutamate release against a steady background of coagonist, excluding the
      possibility of coagonist release. AMPA receptor (AMPAR) stimulation evokes D
      serine release, but it is unknown whether this is a physiological phenomenon
      capable of influencing synaptic responses. In this study, we utilized the intact
      retina to determine whether light-evoked synaptic activity in retinal ganglion
      cells (RGCs) is shaped by a dynamic pool of coagonist. The application of AMPAR
      antagonist abolished light-evoked NMDAR currents, which were rescued by adding
      coagonist to the bath. When NMDA was globally applied to RGCs via bath or
      picospritzing, the coagonist occupancy was also dependent on AMPARs but to a
      lesser extent than that observed during light responses, suggesting a difference
      in extrasynaptic coagonist regulation. By saturating the glutamate binding site
      of NMDARs, we were able to detect released coagonist reaching RGCs during light
      evoked responses. Mutant mice lacking the d-serine-synthesizing enzyme serine
      racemase were deficient in coagonist release. Coagonist release in wild-type
      retinas was notably greater in ON than in OFF responses and depended on AMPARs.
      These findings suggest activity-dependent modulation of coagonist availability,
      particularly D-serine, and may add an extra dimension to NMDAR coincidence
      detection in the retina.

PMID- 22592314
TI  - Selective, isolated proximal tubular angiotensinogen overexpression and salt
      sensitive hypertension.

PMID- 22592316
TI  - Inhibition of Bax protects neuronal cells from oligomeric Abeta neurotoxicity.
AB  - Although oligomeric beta-amyloid (Abeta) has been suggested to have an important
      role in Alzheimer disease (AD), the mechanism(s) of how Abeta induces neuronal
      cell death has not been fully identified. The balance of pro- and anti-apoptotic
      Bcl-2 family proteins (e.g., Bcl-2 and Bcl-w versus Bad, Bim and Bax) has been
      known to have a role in neuronal cell death and, importantly, expression levels
      of these proteins are reportedly altered in the vulnerable neurons in AD.
      However, the roles of apoptotic proteins in oligomeric Abeta-induced cell death
      remain unclear in vivo or in more physiologically relevant models. In addition,
      no study to date has examined whether Bax is required for the toxicity of
      oligomeric Abeta. Here, we found that treatment with oligomeric Abeta increased
      Bim levels but decreased Bcl-2 levels, leading to the activation of Bax and
      neuronal cell death in hippocampal slice culture and in vivo. Furthermore, the
      inhibition of Bax activity either by Bax-inhibiting peptide or bax gene knockout
      significantly prevented oligomeric Abeta-induced neuronal cell death. These
      findings are first to demonstrate that Bax has an essential role in oligomeric
      Abeta-induced neuronal cell death, and that the targeting of Bax may be a
      therapeutic approach for AD.

PMID- 22592318
TI  - p57(KIP2) control of actin cytoskeleton dynamics is responsible for its
      mitochondrial pro-apoptotic effect.
AB  - p57 (Kip2, cyclin-dependent kinase inhibitor 1C), often found downregulated in
      cancer, is reported to hold tumor suppressor properties. Originally described as
      a cyclin-dependent kinase (cdk) inhibitor, p57(KIP2) has since been shown to
      influence other cellular processes, beyond cell cycle regulation, including cell
      death and cell migration. Inhibition of cell migration by p57(KIP2) is attributed
      to the stabilization of the actin cytoskeleton through the activation of LIM
      domain kinase-1 (LIMK-1). Furthermore, p57(KIP2) is able to enhance mitochondrial
      mediated apoptosis. Here, we report that the cell death promoting effect of
      p57(KIP2) is linked to its effect on the actin cytoskeleton. Indeed, whereas
      Jasplakinolide, an actin cytoskeleton-stabilizing agent, mimicked p57(KIP2)'s pro
      apoptotic effect, destabilizing the actin cytoskeleton with cytochalsin D
      reversed p57(KIP2)'s pro-apoptotic function. Conversely, LIMK-1, the enzyme
      mediating p57(KIP2)'s effect on the actin cytoskeleton, was required for
      p57(KIP2)'s death promoting effect. Finally, p57(KIP2-)mediated stabilization of
      the actin cytoskeleton was associated with the displacement of hexokinase-1, an
      inhibitor of the mitochondrial voltage-dependent anion channel, from the
      mitochondria, providing a possible mechanism for the promotion of the
      mitochondrial apoptotic cell death pathway. Altogether, our findings link
      together two tumor suppressor properties of p57(KIP2), by showing that the
      promotion of cell death by p57(KIP2) requires its actin cytoskeleton
      stabilization function.

PMID- 22592317
TI  - Overexpression of Batf induces an apoptotic defect and an associated
      lymphoproliferative disorder in mice.
AB  - Activator protein-1 (AP-1) is a dimeric transcription factor composed of the Jun,
      Fos and Atf families of proteins. Batf is expressed in the immune system and
      participates in AP-1 dimers that modulate gene expression in response to a
      variety of stimuli. Transgenic (Tg) mice overexpressing human BATF in T cells
      were generated using the human CD2 promoter (CD2-HA (hemagglutinin antigen) -
      BATF). By 1 year of age, over 90% of the mice developed a lymphoproliferative
      disorder (LPD). The enlarged lymph nodes characteristic of this LPD contain a
      polyclonal accumulation of T cells with a CD4(+) bias, yet efforts to propagate
      these tumor cells in vitro demonstrate that they do not proliferate as well as
      wild-type CD4(+) T cells. Instead, the accumulation of these cells is likely due
      to an apoptotic defect as CD2-HA-BATF Tg T cells challenged by trophic factor
      withdrawal in vitro resist apoptosis and display a pro-survival pattern of Bcl-2
      family protein expression. As elevated levels of Batf expression are a feature of
      lymphoid tumors in both humans and mice, these observations support the use of
      CD2-HA-BATF mice as a model for investigating the molecular details of apoptotic
      dysregulation in LPD.

PMID- 22592319
TI  - Effect of triptolide on progesterone production from cultured rat granulosa
      cells.
AB  - Triptolide(CAS 38748-32-2), a major active component of Tripterygium wilfordii
      Hook F (TWHF), is known to have multiple pharmacological activities. However,
      studies have also shown that triptolide is highly disrupt to the reproductive
      system by disrupting normal steroid hormone signaling. In the present study, we
      investigated the effect of triptolide (5, 10, or 20 nM for 24 h) on progesterone
      production by rat granulosa cells. Triptolide inhibited both basal and human
      chorionic gonadotropin (HCG)- and 8-bromo-cAMP-stimulated progesterone production
      as revealed by RIA assay. Furthermore, the HCG-evoked increase in cellular cAMP
      content was also inhibited by triptolide, indicating that disruption of the
      cAMP/PKA signaling pathway may mediate the deleterious effects of triptolide on
      progesterone regulation. In addition, triptolide inhibited 25-OH-cholesterol
      stimulated progesterone production, suggesting that activity of the P450 side
      chain cleavage (P450scc) enzyme was also be inhibited by triptolide. Western blot
      and quantitative real-time PCR (qRT-PCR) assays further revealed that triptolide
      decreased mRNA and protein expression of P450scc and the steroidogenic regulatory
      (StAR) protein in granulosa cells. In contrast, cell viability tests using 3-(4,5
      dimethyl-thiazol-2-yl)-2,5- diphenyl-tetrazolium bromide (MTT) indicated that
      triptolide did not cause measurable cell death at doses that suppressed
      steroidogenesis. The reproductive toxicity of triptolide may be caused by
      disruption of cAMP/PKA-mediated expression of a number of progesterone synthesis
      enzymes or regulatory proteins, leading to reduced progesterone synthesis and
      reproductive dysfunction.

PMID- 22592320
TI  - Application of susceptibility weighted imaging (SWI) for evaluation of draining
      veins of arteriovenous malformation: utility of magnitude images.
AB  - INTRODUCTION: The current study evaluated the signal characteristics of
      susceptibility weighted imaging (SWI) of arteriovenous malformation (AVM),
      especially for draining veins. For this purpose, we identified the draining veins
      of the AVM on angiography and evaluated the signal on magnitude image for SWI
      (SWI-mag) and minimum intensity projection image (SWI-minIP). METHODS: Subjects
      were 14 cases with angiographically proven AVM. SWI-mag, SWI-minIP, and time-of
      flight (TOF) magnetic resonance angiography were acquired. For the draining veins
      of the AVM identified on angiography, we analyzed signal intensity on the images
      listed above, and classified it into hyperintensity (hyper), mixed intensity
      (mixed), hypointensity (hypo), and no visualization. RESULTS: On the analysis of
      27 angiographically proven draining veins, 19 draining veins were classified as
      hyper, 3 as mixed, 0 as hypo, and 6 as no visualization on SWI-mag. On TOF
      images, 21 draining veins were classified as hyper, 2 as mixed, 0 as hypo, and 4
      as no visualization, while 6 draining veins did not show hyperintensity on TOF,
      and SWI-mag visualized 3 of these 6 veins as hyper. CONCLUSION: SWI-mag depicted
      most draining veins of AVM as hyperintensity. We speculate that this is mainly
      due to the higher concentration of oxygenated hemoglobin (oxy-Hb) and inflow
      effect of the draining vein. SWI-mag seems to be useful in the analysis and
      follow-up for AVM as the signal on the image may reflect physiological status.

PMID- 22592321
TI  - Mycophenolate mofetil: fully utilizing its benefits for GvHD prophylaxis.
AB  - Mycophenolate mofetil (MMF) has been widely used for the prophylaxis of graft
      versus-host disease (GvHD) in hematopoietic stem cell transplantation (HSCT),
      based on clinical evidence established in organ transplantations. MMF is not a
      cytotoxic, but rather a cytostatic agent, and there have been several reports of
      significant advantages in engraftment as well as greatly reduced stomatitis
      compared to methotrexate (MTX). MMF has been preferred for MTX-free
      immunosuppression, especially in reduced intensity conditioning, but it is
      suitable for GvHD prophylaxis for any type of HSCT. Some clinicians doubt its
      effectiveness, due to the lack of advantage over MTX in acute GvHD prophylaxis,
      especially in myeloablative conditioning. Pharmacokinetics studies of
      mycophenolic acid (MPA), the active form of MMF, show large inter- and intra
      patient variation, which make interpretations of its clinical usefulness
      difficult. Nevertheless, several studies, including ours, have demonstrated that
      relatively higher area under the curve (AUC) of the MPA group leads to
      significant suppression of acute GvHD in prophylactic use. We propose a model
      algorithm for optimal dose finding using therapeutic drug monitoring (TDM) for
      MPA. Preemptive strategies depending on plasma MPA levels could yield more
      effective approaches to GvHD prophylaxis, alternative to MTX.

PMID- 22592322
TI  - Induced pluripotency as a potential path towards iNKT cell-mediated cancer
      immunotherapy.
AB  - Invariant natural killer T (iNKT) cells are characterized by the expression of an
      invariant Valpha14-Jalpha18 paired with Vbeta8/7/2 in mice, and Valpha24-Jalpha18
      with Vbeta11 in humans, that recognizes glycolipids, such as alpha
      galactosylceramide (alpha-GalCer), presented on the MHC class I-like molecule,
      CD1d. iNKT cells act as innate T lymphocytes and serve as a bridge between the
      innate and acquired immune systems. iNKT cells augment anti-tumor responses by
      producing IFN-gamma, which acts on NK cells to eliminate MHC-non-restricted (MHC(
      )) target tumor cells, and on CD8(+) cytotoxic T lymphocytes to directly kill MHC
      restricted (MHC(+)) tumor cells. Thus, when iNKT cells are activated by alpha
      GalCer-pulsed dendritic cells, both MHC(-) and MHC(+) tumor cells can be
      effectively eliminated. Both of these tumor cell types are simultaneously present
      in cancer patients, and at present iNKT cells are only the cell type capable of
      eliminating them. Based on these findings, we have developed iNKT cell-targeted
      adjuvant immunotherapies with strong anti-tumor activity in humans. However, two
      thirds of patients were ineligible for this therapy due to the limited numbers of
      iNKT cells in their bodies. In order to overcome the problem in cancer patients,
      we successfully established a method to generate iNKT cells with adjuvant
      activity from embryonic stem cells (ESCs) and induced pluripotent stem cells
      (iPSCs). In this review, we would like to outline the clinical potential for iNKT
      cells derived from ESCs and iPSCs for cancer immunotherapy, and the technical
      hurdles that must be overcome if we achieve effective ESC/iPSC-mediated cancer
      therapies.

PMID- 22592323
TI  - Workplace-based assessment: raters' performance theories and constructs.
AB  - Weaknesses in the nature of rater judgments are generally considered to
      compromise the utility of workplace-based assessment (WBA). In order to gain
      insight into the underpinnings of rater behaviours, we investigated how raters
      form impressions of and make judgments on trainee performance. Using theoretical
      frameworks of social cognition and person perception, we explored raters'
      implicit performance theories, use of task-specific performance schemas and the
      formation of person schemas during WBA. We used think-aloud procedures and verbal
      protocol analysis to investigate schema-based processing by experienced (N = 18)
      and inexperienced (N = 16) raters (supervisor-raters in general practice
      residency training). Qualitative data analysis was used to explore schema content
      and usage. We quantitatively assessed rater idiosyncrasy in the use of
      performance schemas and we investigated effects of rater expertise on the use of
      (task-specific) performance schemas. Raters used different schemas in judging
      trainee performance. We developed a normative performance theory comprising
      seventeen inter-related performance dimensions. Levels of rater idiosyncrasy were
      substantial and unrelated to rater expertise. Experienced raters made
      significantly more use of task-specific performance schemas compared to
      inexperienced raters, suggesting more differentiated performance schemas in
      experienced raters. Most raters started to develop person schemas the moment they
      began to observe trainee performance. The findings further our understanding of
      processes underpinning judgment and decision making in WBA. Raters make and
      justify judgments based on personal theories and performance constructs. Raters'
      information processing seems to be affected by differences in rater expertise.
      The results of this study can help to improve rater training, the design of
      assessment instruments and decision making in WBA. 

PMID- 22592324
TI  - Purification and characterization of a halophilic alpha-amylase with increased
      activity in the presence of organic solvents from the moderately halophilic
      Nesterenkonia sp. strain F.
AB  - An extracellular halophilic alpha-amylase was purified from Nesterenkonia sp.
      strain F using 80 % ethanol precipitation and Q-Sepharose anion exchange
      chromatography. The enzyme showed a single band with an apparent molecular weight
      of 110 kDa by SDS-PAGE. The amylase exhibited maximal activity at pH 7-7.5, being
      relatively stable at pH 6.5-7.5. Optimal temperature for the amylase activity and
      stability was 45  degrees C. The purified enzyme was highly active in the broad
      range of NaCl concentrations (0-4 M) with optimal activity at 0.25 M NaCl. The
      amylase was highly stable in the presence of 3-4 M NaCl. Amylase activity was not
      influenced by Ca2+, Rb+, Li+, Cs+, Mg2+ and Hg2+, whereas Fe3+, Cu2+, Zn2+ and
      Al3+) strongly inhibited the enzyme activity. The alpha-amylase was inhibited by
      EDTA, but was not inhibited by PMSF and beta-mercaptoethanol. K(m) value of the
      amylase for soluble starch was 6.6 mg/ml. Amylolytic activity of the enzyme was
      enhanced not only by 20 % of water-immiscible organic solvents but also by
      acetone, ethanol and chloroform. Higher concentration (50 %) of the water
      miscible organic solvents had no significant effect on the amylase activity. To
      the best of our knowledge, this is the first report on increased activity of a
      microbial alpha-amylase in the presence of organic solvents.

PMID- 22592326
TI  - Outcomes after percutaneous surgery for patients with multiple sclerosis-related
      trigeminal neuralgia.
AB  - BACKGROUND: Approximately 1% to 2% of patients with multiple sclerosis (MS)
      develop trigeminal neuralgia (TN). Percutaneous surgery is commonly performed in
      medically refractory cases. OBJECTIVE: To analyze the pain outcomes and
      complications of patients with MS-related trigeminal neuralgia (MS-TN) having
      percutaneous surgery. METHODS: Patients having balloon microcompression (BMC; n =
      69) or glycerol rhizotomy (PRGR; n = 67) from 1997 to 2010 were reviewed
      retrospectively. Patients in the 2 groups were similar with regard to age, sex,
      pain location, and pain quality. Mean pain duration was longer in the PRGR group
      (54.6 vs 16 months; P < .001); more patients having BMC had prior surgery (87%
      vs. 48%; P < .001). Outcomes were defined as excellent (no pain, no medications),
      good (no pain with medications), and poor. Median follow-up was 13 months (range,
      0.25-132 months). RESULTS: Ninety-five patients initially had excellent (n = 45,
      33%) or good (n = 50, 37%) outcomes. Pain relief was maintained in 58% of
      patients at 3 months and 28% at 2 years. There was no difference in
      excellent/good outcomes between the surgical groups (hazard ratio = 0.73; P =
      .14). No correlation was noted between pain relief and new or increased facial
      numbness (hazard ratio = 0.78; P = .19). Forty-four BMC patients (64%) had
      additional surgery compared with 36 PRGR patients (54%; P = .19). Complications
      were more frequent after BMC (17.4% vs 3.0%; P < .01). CONCLUSION: Percutaneous
      surgery for patients with MS-TN is less likely to provide pain relief than
      similar operations performed for patients with idiopathic TN. New trigeminal
      deficits did not correlate with better facial pain outcomes, supporting the
      concept that many patients with MS-TN have centrally mediated pain.

PMID- 22592327
TI  - Seizure predictors and control after microsurgical resection of supratentorial
      arteriovenous malformations in 440 patients.
AB  - BACKGROUND: Seizures are a common symptom of supratentorial arteriovenous
      malformations (AVMs), and uncontrolled epilepsy can considerably reduce patient
      quality of life. Potential risk factors for epilepsy in patients with AVMs are
      poorly understood, and the importance of achieving freedom from seizures in their
      surgical treatment remains underappreciated. OBJECTIVE: To characterize risks
      factors for preoperative seizures and factors associated with postoperative
      freedom from seizures in patients with surgically resected supratentorial AVMs.
      METHODS: We analyzed prospectively collected patient data for 440 patients who
      underwent microsurgical resection of supratentorial AVMs at our institution.
      RESULTS: Among 440 patients with supratentorial AVMs, 130 (30%) experienced
      preoperative seizures, and 23 (18%) with seizures progressed to medically
      refractory epilepsy. Seizures were associated with a history of AVM hemorrhage
      (relative risk, 6.65; 95% confidence interval [CI], 3.81-11.6), male sex
      (relative risk, 2.07; 95% CI, 1.26-3.39), and frontotemporal lesion location
      (relative risk, 1.75; 95% CI, 1.05-2.93). After resection, 96% of patients had a
      modified Engel class I outcome, characterized by freedom from seizures (80%) or
      only 1 postoperative seizure (16%; mean follow-up, 20.7 +/- 2.3 months).
      Comparable rates of postoperative seizures were seen in patients with (7%) or
      without (3%) preoperative seizures. AVMs with deep artery perforators were
      significantly associated with postoperative seizures (hazard ratio, 4.35; 95% CI,
      1.61-11.7). CONCLUSION: In the microsurgical treatment of supratentorial AVMs,
      hemorrhage, male sex, and frontotemporal location are associated with higher
      rates of preoperative seizures, whereas deep artery perforators are associated
      with postoperative seizures. Achieving freedom from seizure is an important goal
      that can be achieved in the surgical treatment of AVMs because epilepsy can
      significantly diminish patient quality of life.

PMID- 22592328
TI  - Endoscopic endonasal approach for resection of cranial base chordomas:  outcomes
      and learning curve.
AB  - BACKGROUND: Gross total resection (GTR) of cranial base chordomas represents a
      surgical challenge because of the location, invasiveness, and tumor extension. In
      the past decade, the endoscopic endonasal approach (EEA) has been used with
      notable outcomes. OBJECTIVE: To present the endoscopic endonasal experience in
      the treatment of cranial base chordomas at our institution. METHODS: From April
      2003 to March 2011, 60 patients underwent an EEA for primary (n = 35) or
      previously treated (n = 25) cranial base chordomas. We evaluated the degree of
      GTR and complications. We studied the factors that influenced outcomes and
      compared our surgical results in the early and late years of our experience.
      RESULTS: The overall rate of GTR of cranial base chordomas was 66.7% (82.9% in
      primary and 44% in previously treated patients). The most important limitations
      for GTR were tumor volume greater than 20 cm (P = .042), tumor location in the
      lower clivus with lateral extension (P = .022), and previously treated disease (P
      = .002). The learning curve had a significant impact on GTR, increasing the
      success rate to 88.9% (92.6% in primary patients and 63.6% in previously treated
      patients) during recent years (P < .0001). The most frequent complication was
      cerebrospinal fluid leak (20%) resulting in meningitis in 3.3%. Carotid injuries
      occurred in 2 patients without any resulting deficit. Neurological complications
      included new cranial neuropathies (6.7%) and long tract deficits (1.7%). There
      was no operative mortality in our series. CONCLUSION: For the treatment of
      cranial base chordomas, the EEA is a competitive alternative to transcranial
      approaches with minimal morbidity and high success rates of GTR when performed by
      experienced cranial base surgeons.

PMID- 22592329
TI  - The "July phenomenon" for neurosurgical mortality and complications in teaching
      hospitals: an analysis of more than 850,000 neurosurgical patients in the
      nationwide inpatient sample database, 1998 to 2008.
AB  - BACKGROUND: The evidence of or against the presence of a 'July phenomenon' in
      resident teaching hospitals has been inconsistent. Moreover, there are limited
      data on the "July phenomenon" in the field of neurosurgery. OBJECTIVE: To
      determine whether a "July phenomenon" exists for neurosurgical mortality or
      complications. METHODS: A search of the National Inpatient Sample database from
      1998 to 2008 was performed for all admissions for International Classification of
      Diseases, 9th Revision codes corresponding to nontraumatic hemorrhage, central
      nervous system (CNS) trauma, CNS tumor, and hydrocephalus. Generalized linear
      mixed-model analysis was performed, adjusted for patient demographics and
      hospital characteristics, for the outcomes of mortality and complications for the
      month of July compared with all other months in teaching hospitals. RESULTS:
      Generalized linear mixed-model analysis demonstrated that the risk of dying in
      the month of July vs any other month in a teaching hospital was not statistically
      different for any of the 4 diagnoses: nontraumatic hemorrhage (P = .071), CNS
      trauma category (P = .485), CNS tumor category (P = .578), hydrocephalus category
      (P = .1505). Moreover, the risk of any complication in the month of July vs any
      other month in a teaching hospital was not statistically different for any of the
      4 diagnoses: nontraumatic hemorrhage (P = .529), CNS trauma category (P = .378),
      CNS tumor category (P = .461), and hydrocephalus category (P = .441). The same
      findings were true in an analysis of nonteaching hospitals performed as a
      control. CONCLUSION: No "July phenomenon" was found for neurosurgical mortality
      or complications in patients with nontraumatic hemorrhage, CNS trauma, CNS tumor,
      or hydrocephalus.

PMID- 22592330
TI  - Dissecting aneurysm of the posterior spinal artery:  case report and review of
      the literature.
AB  - BACKGROUND AND IMPORTANCE: Because of their rarity, the pathogenesis and clinical
      features of isolated spinal artery aneurysms are still unclear, and their
      diagnoses and treatments are challenging. We report a case of an isolated
      posterior spinal artery aneurysm and review previous reports thoroughly to
      identify the general features of isolated spinal aneurysms. CLINICAL
      PRESENTATION: A 52-year-old man presented with abdominal pain followed by back
      pain and radiculopathy from subarachnoid hemorrhage in the spinal canal. The
      spinal angiogram demonstrated the presence of a dissecting aneurysm of the
      posterior spinal artery. He was treated by endovascular occlusion of the origin
      of the radiculopial artery and recovered completely. CONCLUSION: Isolated spinal
      artery aneurysms are very rare lesions; however, they should be considered in
      patients with intracranial or spinal subarachnoid hemorrhage without evidence of
      arteriovenous malformations. Spinal aneurysms have different etiologies compared
      with intracranial aneurysms. Cervical aneurysms have worse outcomes than
      thoracolumbar aneurysms. The etiology and location of the lesion and distal flow
      to the lesion should be taken into consideration when planning the treatment.

PMID- 22592331
TI  - Effects of oral and gastric stimulation on appetite and energy intake.
AB  - Appetite is regulated by many factors, including oro-sensory and gastric signals.
      There are many studies on contributions of and possible interaction between
      sensory and gastric stimulation, but there are few studies in humans using
      simultaneous oral and gastric stimulation. We investigated the effect of
      simultaneous, but independently manipulated, oral and gastric stimulation on
      appetite ratings and energy intake. We hypothesized that compared with no
      stimulation, oral and gastric stimulation would equally and additively decrease
      appetite ratings and energy intake. Healthy men (n = 26, 21 +/- 2 years, BMI 22
      +/- 3 kg/m(2)) participated in a randomized crossover trial with four
      experimental conditions and a control condition. Experimental conditions
      consisted of oral stimulation, with either 1 or 8 min modified sham feeding
      (MSF), and gastric stimulation, with either 100 or 800 ml intragastrically
      infused liquid (isocaloric, 99 kcal, 100 ml/min). The control condition consisted
      of no oral or gastric stimulation. Outcome measures were energy intake 30 min
      after the treatment and appetite ratings. Compared with the control condition,
      energy intake decreased significantly after the 8 min/100 ml (19% lower, P =
      0.001) and 8 min/800 ml conditions (15% lower, P = 0.02), but not after the 1
      min/100 ml (14% lower, P = 0.06) and 1 min/800 ml conditions (10% lower, P =
      0.39). There was no interaction of oral and gastric stimulation on energy intake.
      Hunger and fullness differed across all conditions (P <= 0.01). In conclusion,
      duration of oral exposure was at least as important in decreasing energy intake
      as gastric filling volume. Oral and gastric stimulation did not additively
      decrease energy intake. Longer oro-sensory stimulation, therefore, may be an
      important contributor to a lower energy intake.

PMID- 22592332
TI  - Evaluation of oxidative stress in overweight subjects with or without metabolic
      syndrome.
AB  - Although oxidative stress is considered the underlying mechanism by which
      dysfunctional metabolism occurs in obese subjects, there are few studies on
      oxidative stress in overweight subjects. The objective of this study was to
      verify the influence of metabolic syndrome (MetS) on oxidative stress and
      antioxidant defense in overweight subjects. There were 123 subjects (50 in the
      control group and 73 in the overweight group) chosen to participate in this cross
      sectional study. The control group included 50 healthy individuals with a BMI
      between 20 and 24.9 kg/m(2) and without MetS. The overweight group included 73
      subjects with a BMI between 25 and 29.9 kg/m(2). Overweight subjects were divided
      into two groups: with MetS (29 subjects) and without MetS (44 subjects). Control
      group and overweight group subjects without MetS showed no differences in
      oxidative stress parameters and total antioxidant capacity (TRAP). Overweight
      subjects with MetS had higher hydroperoxide concentrations measured by
      chemiluminescence compared to the control group (P < 0.05), higher hydroperoxide
      and hydrogen peroxide concentrations determined by ferrous oxidation-xylenol
      orange assay compared to overweight subjects without MetS (P < 0.001), and higher
      advanced oxidation protein product (AOPP) concentrations (P < 0.001) compared to
      the other groups. AOPP was directly correlated with uric acid concentrations.
      Overweight subjects with MetS had lower TRAP concentrations compared to the
      control group (P < 0.001). In conclusion, this study showed that overweight
      subjects with MetS, in contrast to overweight subjects without MetS, have a redox
      imbalance characterized by increased plasma oxidation and reduced antioxidant
      capacity.

PMID- 22592333
TI  - [Activity in daily living and health outcome. Fact or fiction?].
AB  - Physical activity is strongly associated with good health and in contrast
      physical inactivity is an independent risk factor. From the pathogenetic point of
      view there are strong correlations between physical inactivity and abdominal fat
      mass thus leading to numerous diseases of civilization. Calorie turnover by
      physical activity shows a strong dose-response relationship to the incidence and
      mortality of diseases of civilization, especially of coronary heart disease.
      Activities of daily living contribute slightly to the daily calorie turnover and
      can be documented by accelerometers. The number of steps per day is not only a
      parameter allowing a different inside view to daily routines but is also a key
      for interventional programs. Enhancing the number of steps per day to 10,000, the
      internationally accepted threshold for an active lifestyle, causes a remarkable
      augmentation in health status. From the therapeutic point of view, increasing the
      number of steps lowers the incidence of diabetes type 2 and also affects the
      disease pattern.

PMID- 22592334
TI  - Tracing hidden herbivores: time-resolved non-invasive analysis of belowground
      volatiles by proton-transfer-reaction mass spectrometry (PTR-MS).
AB  - Root herbivores are notoriously difficult to study, as they feed hidden in the
      soil. However, root herbivores may be traced by analyzing specific volatile
      organic compounds (VOCs) that are produced by damaged roots. These VOCs not only
      support parasitoids in the localization of their host, but also may help
      scientists study belowground plant-herbivore interactions. Herbivore-induced VOCs
      are usually analyzed by gas-chromatography mass spectrometry (GC-MS), but with
      this off-line method, the gases of interest need to be preconcentrated, and
      destructive sampling is required to assess the level of damage to the roots. In
      contrast to this, proton-transfer-reaction mass spectrometry (PTR-MS) is a very
      sensitive on-line, non-invasive method. PTR-MS already has been successfully
      applied to analyze VOCs produced by aboveground (infested) plant parts. In this
      review, we provide a brief overview of PTR-MS and illustrate how this technology
      can be applied to detect specific root-herbivore induced VOCs from Brassica
      plants. We also specify the advantages and disadvantages of PTR-MS analyses and
      new technological developments to overcome their limitations.

PMID- 22592335
TI  - Manipulation of chemically mediated interactions in agricultural soils to enhance
      the control of crop pests and to improve crop yield.
AB  - In most agro-ecosystems the organisms that feed on plant roots have an important
      impact on crop yield and can impose tremendous costs to farmers. Similar to
      aboveground pests, they rely on a broad range of chemical cues to locate their
      host plant. In their turn, plants have co-evolved a large arsenal of direct and
      indirect defense to face these attacks. For instance, insect herbivory induces
      the synthesis and release of specific volatile compounds in plants. These
      volatiles have been shown to be highly attractive to natural enemies of the
      herbivores, such as parasitoids, predators, or entomopathogenic nematodes. So far
      few of the key compounds mediating these so-called tritrophic interactions have
      been identified and only few genes and biochemical pathways responsible for the
      production of the emitted volatiles have been elucidated and described. Roots
      also exude chemicals that directly impact belowground herbivores by altering
      their behavior or development. Many of these compounds remain unknown, but the
      identification of, for instance, a key compound that triggers nematode egg
      hatching to some plant parasitic nematodes has great potential for application in
      crop protection. These advances in understanding the chemical emissions and their
      role in ecological signaling open novel ways to manipulate plant exudates in
      order to enhance their natural defense properties. The potential of this approach
      is discussed, and we identify several gaps in our knowledge and steps that need
      to be taken to arrive at ecologically sound strategies for belowground pest
      management.

PMID- 22592336
TI  - p-Cresol: a sex pheromone component identified from the estrous urine of mares.
AB  - Previously it was shown that m- and p-cresols in the urine of mares exhibits a
      temporally reproducible pattern that is dependent on ovarian activity and, thus,
      provides information about the timing of ovulation. New behavioral data
      demonstrate 1) that stallions spend significantly more time sniffing p-cresol as
      compared to o-, and m-cresols, and, 2) that the extent of stallions' erections
      differ significantly in response to different types of samples. The lowest
      erection level was recorded for the pure-water control, a moderate erection level
      was elicited by the urine of diestrous mares, and the highest erection level was
      elicited by urine of a diestrous mare containing synthetic p-cresol at a quantity
      equivalent to half of the amount of p-cresol found in the urine of estrous mares.
      Consequently, p-cresol is at least one of the components of a horse sex
      pheromone.

PMID- 22592337
TI  - A facile one-pot synthesis of ruthenium hydroxide nanoparticles on magnetic
      silica: aqueous hydration of nitriles to amides.
AB  - One-pot synthesis of ruthenium hydroxide nanoparticles on magnetic silica is
      described which involves the in situ generation of magnetic silica
      (Fe(3)O(4)@SiO(2)) and ruthenium hydroxide immobilization; the hydration of
      nitriles occurs in high yield and excellent selectivity using this catalyst which
      proceeds exclusively in aqueous medium under neutral conditions.

PMID- 22592338
TI  - Dynamics of one electron in a nonlinear disordered chain.
AB  - In this paper we report new numerical results on the disordered Schrodinger
      equation with nonlinear hopping. By using a classical harmonic Hamiltonian and
      the Su-Schrieffer-Heeger  approximation we write an effective Schrodinger
      equation. This model with off-diagonal nonlinearity allows us to study the
      interaction of one electron and acoustical phonons. We solve the effective
      Schrodinger equation with nonlinear hopping for an initially localized wavepacket
      by using a predictor-corrector Adams-Bashforth-Moulton method. Our results
      indicate that the nonlinear off-diagonal term can promote a long-time
      subdiffusive regime similar to that observed in models with diagonal
      nonlinearity.

PMID- 22592339
TI  - [Special topic: inflammations of the ocular surface].

PMID- 22592340
TI  - [Anti-inflammatory treatment in dry eye disease].
AB  - Dry-eye is a multifactorial disease consisting of different pathomechanisms
      including instability of the tearfilm, increase of tearfilm osmolarity and most
      importantly inflammation of the ocular surface. In this context numerous
      signalling pathways and related immune mechanisms were identified all pointing
      towards autoimmune reactions as key parameters within this complex system. As
      autoimmunity tends to act independently from regulatory mechanisms, inhibition of
      related inflammatory processes is crucial in dry-eye therapy. Currently
      therapeutic agents such as steroids, cyclosporin, antibiotics, omega-3 and -6
      fatty acids, etc. are available and readily used in daily practice. However,
      these therapies possess functional or legal restrictions that may limit their
      application. New strategies such as anti-lymphangiogenic therapies may have the
      potential to substitute or enhance current treatments. Independent of any anti
      inflammatory therapy a detailed examination of the individual patient is
      necessary due to the complexity of the disease to provide individual and
      successful treatment.

PMID- 22592341
TI  - [Meibomian gland dysfunction].
AB  - Meibomian gland dysfunction (MGD) is a chronic disease, usually caused by
      obstruction of the secretory Meibomian glands. The subsequent reduction of gland
      secretion results in a decreased amount of lipids in the tear film. This results
      in a faster evaporation of the tear film and thus an evaporative dry eye. MGD
      alone is responsible for about 60% of all cases in combination with aqueous
      deficiency for a further 20% of dry eyes. While in Europe up to 20% of the
      population are suffering from MDD, this is true in Asia for over 60% of the
      population. MGD is more common in women and it incidence increases with age. It
      is influenced by the hormonal status as well as chemical and mechanical noxious
      stimuli. Additional risk factors include various skin diseases such as rosacea,
      acne or atopy. To diagnose MGD, particular attention should be paid to changes in
      the lid margin such as plugging or pouting of the ducts, thickening and
      telangiectasia. However, most important is the diagnostic expression of the
      glands. At first it should be assessed whether secretion can be caused by
      pressure to the eyelid against the globe and secondly the quality of the
      expressed secretions should be evaluated. MGD should be treated according to the
      severity of the disease. While in mild stages instructions for lid margin
      hygiene, warming and massage in combination with artificial tears might be
      sufficient, in more severe stages oral tetracyclin derivatives and anti
      inflammatory eye drops such as steroids or CSA are necessary for successful
      treatment.

PMID- 22592342
TI  - [Contact lenses and keratitis].
AB  - Keratitis is a rare but important and possibly sight threatening complication of
      Contact Lens wearing. Despite of the number of only about 1.7 keratitis cases per
      ophthalmolgist per year, this serious side effect needs knowledge and special
      diagnosis and treatment. Global changes of infectious agents and increase of
      previously unsuspicious pathogens in combination with a high degress of non
      compliance indicate that Contact Lens wearing must be accompanied careful
      ophthalmologist's medical care and after-care.

PMID- 22592343
TI  - [Acanthamoeba keratitis--a rare and often late diagnosed disease].
AB  - In 83-93% of the cases of acanthamoeba keratitis the patients are contact lens
      wearers. Acanthamoeba keratitis is diagnosed--with descending order of
      sensitivity and specificity--through polymerase chain reaction (PCR), confocal
      biomicroscopy, in-vitro cultivation and histopathological examination. The
      typical clinical appearance of acanthamoeba keratitis includes pseudodendritic
      epitheliopathy, perineuritis, ring infiltrate or multifocal stromal infiltrates
      and in some cases limbitis with infiltration of the conjunctiva and/or sterile
      anterior uveitis. Information on reliability and efficacy of the medical/surgical
      therapy for acanthamoeba keratitis has only been published for case series and It
      has not been verified through randomised controlled clinical studies so far. By
      early diagnosis, using triple-topical therapy (polyhexamid,
      propamidinisoethionat, neomycin) acanthamoeba keratitis often heals
      appropriately. However, even if diagnosed early, topical therapy should be
      continued for 1 year. In therapy-resistant cases cryotherapy, amniotic membrane
      transplantation, cross-linking therapy, and therapeutic keratoplasty are
      performed. The prognosis of keratoplasty following acanthamoeba keratitis is more
      favourable when there were no signs of infection at least during the preceding 3
      months.

PMID- 22592344
TI  - [Bacterial conjunctivitis--diagnosis and therapy update].
AB  - Acute bacterial conjunctivitis is a common health-care issue for the general
      practitioner and the ophthalmologist. Signs and symptoms usually allow a correct
      diagnosis without conjunctival swab. Primary microbiological investigations are
      recommended in newborns, immunocompromised patients and cases of hyperacute
      conjunctivitis. Of concern are methicillin-resistant Staphylococcus aureus
      strains which have been isolated with increasing frequency in the last few years.
      Studies have demonstrated the faster clinical and microbiological cure of acute
      bacterial conjunctivitis with topical antibiotics. However, the development of
      resistance of the typical germs to all of the antibiotic groups is alarming and
      should influence therapeutic behaviour. Fluoroquinolones show good activity in
      the treatment of acute bacterial conjunctivitis but should be saved for severe
      infections due to its broad spectrum of activity. Antibiotics such as gentamycin,
      tobramycin, and azithromycin should be preferred. Considering the high
      spontaneous healing rate of acute conjunctivitis, delayed topical antibiotics in
      case of persistence after 3-4 days, or treatment without antibiotics using
      artificial tears and eye bathings may be considered. Additive anti-inflammatory
      drugs are generally not recommended. Chronic-recurrent follicular conjunctivitis
      necessitates testing for Chlamydia, and in case of a positive result, systemic
      antibiotic treatment of patient and sexual partner.

PMID- 22592345
TI  - [Ocular involvement in Stevens-Johnson syndrome and toxic epidermal necrolysis].
AB  - Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare
      severe reactions of skin and mucous membranes. They are considered as a single
      disease entity with differing severities and are mainly induced by drugs, less
      frequently by infections. In 50% of the patients ocular complications occur,
      which can lead to blindness in the absence of immediate ophthalmological
      treatment. The acute pattern, the unpredictable course and extreme variations in
      the manifestation of complications require an interdisciplinary treatment. Early
      diagnosis and initiation of an intensive lubricating and anti-inflammatory
      surface care are of utmost importance for the best visual outcome. This article
      is intended to help ophthalmologists towards a better understanding and
      interpretation of clinical signs of these conditions with the goal to achieve
      substantial improvements in visual outcome and of course the patient's quality of
      life.

PMID- 22592346
TI  - [Eye banks].

PMID- 22592347
TI  - [Retinopathy of prematurity].

PMID- 22592349
TI  - Self-assembly driven by an aromatic primary amide motif.
AB  - Primary amides are unique supramolecular synthons possessing two hydrogen donors
      and two hydrogen acceptors. By interacting in a complementary fashion, primary
      amides reliably generate two-dimensional hydrogen bonded networks that differ
      from conventional hydrogen bonded structures such as carboxylic acid dimers or
      one-dimensional secondary amide chains. This feature permits the design of
      sophisticated supramolecular assemblies based on primary amides (especially
      aromatic amides). Several interesting crystal structures have been constructed
      utilizing primary amides, although such structures have been applied only in the
      field of crystal engineering because the networks strongly favor crystallization.
      Expansion of the applications of primary amides to liquid crystals and self
      assembly in solution requires an appropriate balance between primary amide-based
      hydrogen bonding and other noncovalent interactions. This perspective article
      reviews the key hydrogen bonding properties of primary amides determined from
      crystal structure studies, and a variety of supramolecular assemblies involving
      primary amides are discussed. A new strategy for overcoming crystallinity and
      solubility issues is proposed, involving introduction of a trifluoromethyl group
      at the ortho position of the aromatic primary amide. Such substitutions produce
      highly processable primary amides, while maintaining the two-dimensional hydrogen
      bonded network. Examples of self-assembly using 2-trifluoromethylbenzamide
      demonstrate its usefulness in self-assembly.

PMID- 22592348
TI  - Diagnostic value of optical coherence tomography for intracranial pressure in
      idiopathic intracranial hypertension.
AB  - BACKGROUND: Idiopathic intracranial hypertension (IIH) is a condition of raised
      intracranial pressure (ICP) in the absence of space-occupying lesions or other
      known etiology. It primarily affects young obese females, and potentially causes
      permanent visual loss due to papilledema and secondary optic atrophy. The aim of
      this study was to evaluate the diagnostic value of optical coherence tomography
      (OCT) as a marker for CSF opening pressure in patients with idiopathic
      intracranial hypertension (IIH). METHODS: We conducted a case-control study of 20
      newly diagnosed, 21 long-term IIH patients, and 20 healthy controls.
      Investigations included measurement of peripapillary retinal nerve fiber layer
      thickness (RNFLT) and total retinal thickness (RT), automated visual field
      testing, and measurement of CSF opening pressure. An OCT elevation diagram was
      developed as a new diagnostic tool. The diagnostic ability of OCT as a marker of
      increased ICP (> 25 cmH(2)O) was investigated using multiple regression and
      receiver operating characteristic (ROC) curves. RESULTS: OCT elevation diagrams
      showed that in 60 % of patients newly diagnosed with IIH and in 10 % of patients
      with long-term IIH, 50 % or more of the OCT scans (RT and RNFLT) were above
      normal. The percentage of abnormal OCT scans was significantly associated with
      increased ICP (p < 0.0001). Estimated areas under the ROC curves increased from
      77.1 to 86.9 by including OCT in multiple regressions. Autoperimetry pattern
      standard deviation was significantly increased (p = 0.0005) and mean deviation
      was significantly decreased (p = 0.0005) in IIH patients as compared to healthy
      controls. CONCLUSIONS: Increased peripapillary retinal thickness measured by OCT
      is associated with increased ICP in newly diagnosed IIH patients. OCT may thus
      serve as a valuable supplement to subjective assessment of papilledema in
      patients suspected of having IIH. In long-term IIH patients who have previously
      been treated, OCT appears to be of limited value in predicting ICP.

PMID- 22592350
TI  - Distribution and accumulation of metals in tadpoles inhabiting the metalliferous
      streams of eastern Chalkidiki, northeast Greece.
AB  - The present study investigates the accumulation of heavy metals [copper (Cu),
      lead (Pb), zinc (Zn), magnesium (Mn), cadmium (Cd), nickel (Ni), and chromium
      (Cr)] in tadpoles inhabiting the metalliferous streams flowing within the
      Asprolakkas River basin (northeast Chalkidiki peninsula, Greece) and the effect
      of potentially harmful elements in stream water and sediment on the corresponding
      levels in their tissue. Animals were collected from six sampling sites influenced
      by a wide range of surface water and stream sediment trace element
      concentrations. The results of the chemical analyses showed that tadpoles
      accumulated significant levels of all of the examined metals. The range of whole
      body mean measured concentrations were (in dry mass) as follows: Cu (46-182
      mg/kg), Pb (103-4,490 mg/kg), Zn (494-11,460 mg/kg), Mn (1,620-13,310 mg/kg), Cd
      (1.2-82 mg/kg), Ni (57-163 mg/kg), and Cr (38-272 mg/kg). The mean concentrations
      of Pb, Zn, Mn, Ni, Cr, and Cd in Kokkinolakkas stream, which drains a currently
      active mining area, were the highest ever reported in tadpoles. Our results
      indicate that whole-body levels of Pb, Zn, Cu, and Cd increase with stream
      sediment concentrations and that these organisms tend to accumulate metals bound
      to Fe and Mn oxides. In addition, high dissolved concentrations and significant
      concentrations associated with more labile geochemical phases of sediments for
      specific metals were contributing factors determining whole-body levels. Given
      the observed bioconcentration factors, as well as the correlation with sediment
      concentrations, it is proposed that these organisms could be considered as
      bioindicators of environmental contamination and may be used for monitoring
      purposes within this metal-rich zone and, perhaps, within other rivers affected
      by metal mining.

PMID- 22592351
TI  - Direct visualization of solution morphology of cellulose in ionic liquids by
      conventional TEM at room temperature.
AB  - Taking advantage of the negligible vapor pressure and dissolving features of
      ionic liquids (ILs), the solution morphology and dissolution process of cellulose
      in ILs have been visualized directly by conventional transmission electron
      microscopy (TEM) at room temperature for the first time.

PMID- 22592352
TI  - Literacy-sensitive intervention for COPD patients.

PMID- 22592353
TI  - Cardiac complications of unwitting co-injection of quinine/quinidine with heroin
      in an intravenous drug user.
AB  - Adulterants "cut into" street heroin are common and often not detected by
      standard urine toxicology screening; however, their unwitting co-injection may
      have clinical consequences. We report a case of accelerated atrioventricular
      junctional arrhythmia that we determined to have been caused by quinine/quinidine
      cut into heroin. While identification and discontinuation of the offending agent
      helps confirm the diagnosis and is the treatment of choice, this is often
      complicated by the individual's dependence on the street drug in which the
      adulterant is mixed. This case highlights the need for clinicians to be aware of
      common adulterants, to know how to test for them, and to consider them as
      possible causes of medical complications in individuals who use drugs.

PMID- 22592354
TI  - Teaching the use of respiratory inhalers to hospitalized patients with asthma or
      COPD: a randomized trial.
AB  - BACKGROUND: Hospitalized patients frequently misuse their respiratory inhalers,
      yet it is unclear what the most effective hospital-based educational intervention
      is for this population. OBJECTIVE: To compare two strategies for teaching inhaler
      use to hospitalized patients with asthma or chronic obstructive pulmonary disease
      (COPD). DESIGN: A Phase-II randomized controlled clinical trial enrolled
      hospitalized adults with physician diagnosed asthma or COPD. PARTICIPANTS:
      Hospitalized adults (age 18 years or older) with asthma or COPD. INTERVENTIONS:
      Participants were randomized to brief intervention [BI]: single-set of verbal and
      written step-by-step instructions, or, teach-to-goal [TTG]: BI plus repeated
      demonstrations of inhaler use and participant comprehension assessments (teach
      back). MAIN MEASURES: The primary outcome was metered-dose inhaler (MDI) misuse
      post-intervention (<75% steps correct). Secondary outcomes included Diskus(r)
      misuse, self-reported inhaler technique confidence and prevalence of 30-day
      health-related events. KEY RESULTS: Of 80 eligible participants, fifty (63%) were
      enrolled (BI n=26, TTG n=24). While the majority of participants reported being
      confident with their inhaler technique (MDI 70%, Diskus(r) 94%), most misused
      their inhalers pre-intervention (MDI 62%, Diskus(r) 78%). Post-intervention MDI
      misuse was significantly lower after TTG vs. BI (12.5 vs. 46%, p=0.01). The
      results for Diskus(r) were similar and approached significance (25 vs. 80%,
      p=0.05). Participants with 30-day acute health-related events were less common in
      the group receiving TTG vs. BI (1 vs. 8, p=0.02). CONCLUSIONS: TTG appears to be
      more effective compared with BI. Patients over-estimate their inhaler technique,
      emphasizing the need for hospital-based interventions to correct inhaler misuse.
      Although TTG was associated with fewer post-hospitalization health-related
      events, larger, multi-centered studies are needed to evaluate the durability and
      clinical outcomes associated with this hospital-based education.

PMID- 22592355
TI  - Judging whether a patient is actually improving: more pitfalls from the science
      of human perception.
AB  - Fallible human judgment may lead clinicians to make mistakes when assessing
      whether a patient is improving following treatment. This article provides a
      narrative review of selected studies in psychology that describe errors that
      potentially apply when a physician assesses a patient's response to treatment.
      Comprehension may be distorted by subjective preconceptions (lack of double
      blinding). Recall may fail through memory lapses (unwanted forgetfulness) and
      tacit assumptions (automatic imputation). Evaluations may be further compromised
      due to the effects of random chance (regression to the mean). Expression may be
      swayed by unjustified overconfidence following conformist groupthink (group
      polarization). An awareness of these five pitfalls may help clinicians avoid some
      errors in medical care when determining whether a patient is improving.

PMID- 22592356
TI  - Reducing health disparities or improving minority health? The end determines the
      means.

PMID- 22592357
TI  - The risks for falls and fractures in multiple sclerosis.

PMID- 22592358
TI  - How many HITS are too many?: The use of accelerometers to study sports-related
      concussion.

PMID- 22592359
TI  - Proteinuria and clinical outcomes after ischemic stroke.
AB  - OBJECTIVES: The impact of chronic kidney disease (CKD) on clinical outcomes after
      acute ischemic stroke is still not fully understood. The aim of the present study
      was to elucidate how CKD and its components, proteinuria and low estimated
      glomerular filtration rate (eGFR), affect the clinical outcomes after ischemic
      stroke. METHODS: The study subjects consisted of 3,778 patients with first-ever
      ischemic stroke within 24 hours of onset from the Fukuoka Stroke Registry. CKD
      was defined as proteinuria or low eGFR (<60 mL/min/m(2)) or both. The study
      outcomes were neurologic deterioration (>=2-point increase in the NIH Stroke
      Scale during hospitalization), in-hospital mortality, and poor functional outcome
      (modified Rankin Scale score at discharge of 2 to 6). The effects of CKD,
      proteinuria, and eGFR on these outcomes were evaluated using a multiple logistic
      regression analysis. RESULTS: CKD was diagnosed in 1,320 patients (34.9%). In the
      multivariate analyses after adjusting for confounding factors, patients with CKD
      had significantly higher risks of neurologic deterioration, in-hospital
      mortality, and poor functional outcome (p <0.001 for all). Among the CKD
      components, a higher urinary protein level was associated with an elevated risk
      of each outcome (p for trend < 0.001 for all), but no clear relationship between
      the eGFR level and each outcome was found. CONCLUSIONS: CKD is an important
      predictor of poor clinical outcomes after acute ischemic stroke. Proteinuria
      independently contributes to the increased risks of neurologic deterioration,
      mortality, and poor functional outcome, but the eGFR may not be relevant to these
      outcomes.

PMID- 22592360
TI  - Highly fatal fast-channel syndrome caused by AChR epsilon subunit mutation at the
      agonist binding site.
AB  - OBJECTIVE: To characterize the molecular basis of a novel fast-channel congenital
      myasthenic syndrome. METHODS: We used the candidate gene approach to identify the
      pathogenic mutation in the acetylcholine receptor (AChR) epsilon subunit,
      genetically engineered the mutant AChR into HEK cells, and evaluated the level of
      expression and kinetic properties of the mutant receptor. RESULTS: An 8-year-old
      boy born to consanguineous parents had severe myasthenic symptoms since birth. He
      is wheelchair bound and pyridostigmine therapy enables him to take only a few
      steps. Three similarly affected siblings died in infancy. He carries a homozygous
      p.W55R mutation at the alpha/epsilon subunit interface of the AChR agonist
      binding site. The mutant protein expresses well in HEK cells. Patch-clamp
      analysis of the mutant receptor expressed in HEK cells reveals 30-fold reduced
      apparent agonist affinity, 75-fold reduced apparent gating efficiency, and
      strikingly attenuated channel opening probability (P(open)) over a range agonist
      concentrations. CONCLUSION: Introduction of a cationic Arg into the anionic
      environment of alpha/epsilon AChR binding site hinders stabilization of cationic
      ACh by aromatic residues and accounts for the markedly perturbed kinetic
      properties of the receptor. The very low P(open) explains the poor response to
      pyridostigmine and the high fatality of the disease.

PMID- 22592361
TI  - Brain atrophy accelerates cognitive decline in cerebral small vessel disease: the
      LADIS study.
AB  - OBJECTIVE: To examine the independent contributions and combined interactions of
      medial temporal lobe atrophy (MTA), cortical and subcortical atrophy, and white
      matter lesion (WML) volume in longitudinal cognitive performance. METHODS: A
      total of 477 subjects with age-related WML were evaluated with brain MRI and
      annual neuropsychological examinations in 3-year follow-up. Baseline MRI
      determinants of cognitive decline were analyzed with linear mixed models
      controlling for multiple confounders. RESULTS: MTA and subcortical atrophy
      predicted significantly steeper rate of decline in global cognitive measures as
      well as compound scores for psychomotor speed, executive functions, and memory
      after adjusting for age, gender, education, lacunes/infarcts, and WML volume.
      Cortical atrophy independently predicted decline in psychomotor speed. WML volume
      remained significantly associated with cognitive decline even after controlling
      for the atrophy scores. Moreover, significant synergistic interactions were found
      between WML and atrophy measures in overall cognitive performance across time and
      the rate of cognitive decline. Synergistic effects were also observed between
      baseline lacunar infarcts and all atrophy measures on change in psychomotor
      speed. The main results remained robust after exclusion of subjects with clinical
      stroke or incident dementia, and after additional adjustments for progression of
      WML and lacunes. CONCLUSIONS: Brain atrophy and WML are independently related to
      longitudinal cognitive decline in small vessel disease. MTA, subcortical, and
      cortical atrophy seem to potentiate the effect of WML and lacunes on cognitive
      decline.

PMID- 22592362
TI  - Positional periodic alternating vertical nystagmus with PCA-Tr antibodies in
      Hodgkin lymphoma.

PMID- 22592364
TI  - Personalized medicine in deep brain stimulation through utilization of neural
      oscillations.

PMID- 22592363
TI  - Mobile stroke unit for diagnosis-based triage of persons with suspected stroke.
AB  - BACKGROUND: In this feasibility study, we tested whether prehospital diagnostic
      stroke workup enables rational decision-making regarding treatment and the target
      hospital in persons with suspected stroke. METHODS: A mobile stroke unit that
      delivers imaging (including multimodal brain imaging with CT angiography and CT
      perfusion), point-of-care-laboratory analysis, and neurologic expertise directly
      at the emergency site was analyzed for its use in prehospital diagnosis-based
      triage of suspected stroke patients. RESULTS: We present 4 complementary cases
      with suspected stroke who underwent prehospital diagnostic workup that enabled
      direct diagnosis-based treatment decisions and reliable triage regarding the most
      appropriate medical facility for that individual, e.g., a primary hospital vs
      specialized centers of a tertiary hospital. CONCLUSIONS: This preliminary report
      demonstrates the feasibility of prehospital diagnostic stroke workup for
      immediate etiology-specific decision-making regarding the necessary time
      sensitive stroke treatment and the most appropriate target hospital.

PMID- 22592365
TI  - The "almost magical" mobile stroke unit revolution.

PMID- 22592367
TI  - Utility of MRI in spinal arteriovenous fistula.
AB  - OBJECTIVE AND BACKGROUND: Spinal arteriovenous fistula (SAVF) is a rare but
      treatable cause of myelopathy. The diagnostic accuracy of MRI for detecting SAVF
      is unknown. Our objective was to determine the sensitivity and specificity of MRI
      in the diagnosis SAVF and characterize its radiographic features. METHODS: We
      conducted a retrospective case-control study of all SAVF treated at our
      institution from 1995 to 2010, including patients who presented with myelopathy,
      had MRIs available for review, and underwent either spinal angiogram or had
      another diagnosis confirming test. Two blinded board-certified radiologists
      reviewed a series of MRIs and listed the most likely diagnoses, radiologic
      findings, and recommended follow-up. Sensitivities and specificities of MRI
      compared to spinal angiogram were calculated. We additionally conducted a
      literature review of cases describing MRI findings in spinal dural and
      perimedullary arteriovenous fistula. RESULTS: We identified 36 cases of SAVF
      (median age 56, 67% male) and 32 controls (median age 54, 44% male). MRI was
      sensitive in identifying SAVF as the primary diagnosis in 94% (radiologist A, 95%
      confidence interval [CI] 0.87-1.02) and 89% (radiologist B, 95% CI 0.79-0.99) of
      cases. The sensitivity of spinal cord T2 hyperintensity or flow voids was 100%
      and the specificity of T2 hyperintensity and flow voids was 97%. CONCLUSIONS:
      Among patients with myelopathy, spinal angiography is mandatory in the presence
      of both T2 hyperintensity and flow voids but may be unnecessary if both of these
      findings are absent.

PMID- 22592366
TI  - Family history of Alzheimer disease predicts hippocampal atrophy in healthy
      middle-aged adults.
AB  - OBJECTIVE: To evaluate the longitudinal influence of family history (FH) of
      Alzheimer disease (AD) and apolipoprotein E epsilon4 allele (APOE4) on brain
      atrophy and cognitive decline over 4 years among asymptomatic middle-aged
      individuals. METHODS: Participants were cognitively healthy adults with (FH+) (n
      = 60) and without (FH-) (n = 48) a FH of AD (mean age at baseline 54 years)
      enrolled in the Wisconsin Registry for Alzheimer's Prevention. They underwent
      APOE genotyping, cognitive testing, and an MRI scan at baseline and 4 years
      later. A covariate-adjusted voxel-based analysis interrogated gray matter (GM)
      modulated probability maps at the 4-year follow-up visit as a function of FH and
      APOE4. We also examined the influence of parent of origin on GM atrophy. Parallel
      analyses investigated the effects of FH and APOE4 on cognitive decline. RESULTS:
      Neither FH nor APOE4 had an effect on regional GM or cognition at baseline.
      Longitudinally, a FH * APOE4 interaction was found in the right posterior
      hippocampus, which was driven by a significant difference between the FH+ and FH-
      subjects who were APOE4-. In addition, a significant FH main effect was observed
      in the left posterior hippocampus. No significant APOE4 main effects were
      detected. Persons with a maternal history of AD were just as likely as those with
      a paternal history of AD to experience posterior hippocampal atrophy. There was
      no longitudinal decline in cognition within the cohort. CONCLUSION: Over a 4-year
      interval, asymptomatic middle-aged adults with FH of AD exhibit significant
      atrophy in the posterior hippocampi in the absence of measurable cognitive
      changes. This result provides further evidence that detectable disease-related
      neuroanatomic changes do occur early in the AD pathologic cascade.

PMID- 22592368
TI  - Faster, slower, but never better: mutations of the skeletal muscle acetylcholine
      receptor.

PMID- 22592369
TI  - Anti-JC virus antibodies in a large German natalizumab-treated multiple sclerosis
      cohort.
AB  - OBJECTIVE: To investigate the rate of seropositivity of anti-JC virus (JCV)
      antibodies in a German multiple sclerosis (MS) cohort treated with natalizumab in
      the postmarketing setting and to assess anti-JCV serostatus in samples obtained
      before diagnosis of progressive multifocal leukoencephalopathy (PML). METHODS:
      This was a blinded, retrospective cross-sectional and longitudinal analysis for
      anti-JCV antibodies using a confirmatory 2-step ELISA on 2,782 blood samples
      obtained from 2,253 patients nationwide for routine testing for anti-natalizumab
      antibodies during open-label treatment between 2007 and 2010. RESULTS: Of the
      natalizumab-treated patients with MS, 58.8% tested positive for anti-JCV
      antibodies. The rate of seropositivity was higher in males and increased with
      age, with a plateau between age intervals 20-29 and 30-39 years. In longitudinal
      analyses, 19 of 194 (9.8%) patients converted from anti-JCV antibody-negative to
      seropositive status over 7.7 months; 4.7% reverted from antibody-positive to
      seronegative status over 7.9 months. Antibody levels, especially in the latter
      group, were low, indicating fluctuations around the lower cut point of the assay.
      Neither anti-JCV serostatus nor antibody levels were associated with
      immunosuppressive pretreatment, duration of natalizumab treatment, or anti
      natalizumab antibodies. All samples obtained from 10 patients who developed PML
      were seropositive (13 samples before PML diagnosis [2.0-37.6 months]; 2 samples
      at diagnosis). Antibody levels in these samples were higher than those in samples
      from seropositive patients who did not develop PML. CONCLUSIONS: These data argue
      for the potential clinical utility of JCV serology for PML risk stratification.
      However, further investigations of fluctuations in serostatus and of antibody
      levels for a more precise understanding of the predictive value are warranted.

PMID- 22592371
TI  - The cerebro-renal interaction in stroke neurology.

PMID- 22592370
TI  - Cognitive effects of one season of head impacts in a cohort of collegiate contact
      sport athletes.
AB  - OBJECTIVE: To determine whether exposure to repetitive head impacts over a single
      season negatively affects cognitive performance in collegiate contact sport
      athletes. METHODS: This is a prospective cohort study at 3 Division I National
      Collegiate Athletic Association athletic programs. Participants were 214 Division
      I college varsity football and ice hockey players who wore instrumented helmets
      that recorded the acceleration-time history of the head following impact, and 45
      noncontact sport athletes. All athletes were assessed prior to and shortly after
      the season with a cognitive screening battery (ImPACT) and a subgroup of athletes
      also were assessed with 7 measures from a neuropsychological test battery.
      RESULTS: Few cognitive differences were found between the athlete groups at the
      preseason or postseason assessments. However, a higher percentage of the contact
      sport athletes performed more poorly than predicted postseason on a measure of
      new learning (California Verbal Learning Test) compared to the noncontact
      athletes (24% vs 3.6%; p < 0.006). On 2 postseason cognitive measures (ImPACT
      Reaction Time and Trails 4/B), poorer performance was significantly associated
      with higher scores on several head impact exposure metrics. CONCLUSION:
      Repetitive head impacts over the course of a single season may negatively impact
      learning in some collegiate athletes. Further work is needed to assess whether
      such effects are short term or persistent.

PMID- 22592372
TI  - White matter imaging contributes to the multimodal diagnosis of frontotemporal
      lobar degeneration.
AB  - OBJECTIVE: To evaluate the distribution of white matter (WM) disease in
      frontotemporal lobar degeneration (FTLD) and Alzheimer disease (AD) and to
      evaluate the relative usefulness of WM and gray matter (GM) for distinguishing
      these conditions in vivo. METHODS: Patients were classified as having FTLD (n =
      50) or AD (n = 42) using autopsy-validated CSF values of total-tau:beta-amyloid
      (t-tau:Abeta(1-42)) ratios. Patients underwent WM diffusion tensor imaging (DTI)
      and volumetric MRI of GM. We employed tract-specific analyses of WM fractional
      anisotropy (FA) and whole-brain GM density analyses. Individual patient
      classification was performed using receiver operator characteristic (ROC) curves
      with FA, GM, and a combination of the 2 modalities. RESULTS: Regional FA and GM
      were significantly reduced in FTLD and AD relative to healthy seniors. Direct
      comparisons revealed significantly reduced FA in the corpus callosum in FTLD
      relative to AD. GM analyses revealed reductions in anterior temporal cortex for
      FTLD relative to AD, and in posterior cingulate and precuneus for AD relative to
      FTLD. ROC curves revealed that a multimodal combination of WM and GM provide
      optimal classification (area under the curve = 0.938), with 87% sensitivity and
      83% specificity. CONCLUSIONS: FTLD and AD have significant WM and GM defects. A
      combination of DTI and volumetric MRI modalities provides a quantitative method
      for distinguishing FTLD and AD in vivo.

PMID- 22592373
TI  - Subthalamic deep brain stimulation at individualized frequencies for Parkinson
      disease.
AB  - OBJECTIVES: The oscillation model of Parkinson disease (PD) states that, in the
      subthalamic nucleus (STN), increased theta (4-10 Hz) and beta (11-30 Hz)
      frequencies were associated with worsening whereas gamma frequencies (31-100 Hz)
      were associated with improvement of motor symptoms. However, the peak STN
      frequency in each band varied widely from subject to subject. We hypothesized
      that STN deep brain stimulation (DBS) at individualized gamma frequencies would
      improve whereas theta or beta frequencies would worsen PD motor signs. METHODS:
      We prospectively studied 13 patients with PD. STN local field potential (LFP) was
      recorded after electrode implantations, in the OFF and then in ON dopaminergic
      medication states while patients performed wrist movements. Six individual peak
      frequencies of the STN LFP power spectra were obtained: the greatest decrease in
      theta and beta and greatest increase in gamma frequencies in the ON state (MED)
      and during movements (MOVE). Eight DBS frequencies were applied including 6 MED
      and MOVE frequencies, high frequency (HF) used for chronic stimulation, and no
      stimulation. The patients were assessed using the motor Unified Parkinson's
      Disease Rating Scale (mUPDRS). RESULTS: STN DBS at gamma frequencies (MED and
      MOVE) and HF significantly improved mUPDRS scores compared to no stimulation and
      both gamma frequencies were not different from HF. DBS at theta and beta
      frequencies did not worsen mUPDRS scores compared to no stimulation. CONCLUSION:
      Short-term administration of STN DBS at peak dopamine-dependent or movement
      related gamma frequencies were as effective as HF for reducing parkinsonian motor
      signs but DBS at theta and beta frequencies did not worsen PD motor signs.
      CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that STN DBS
      at patient-specific gamma frequencies and at usual high frequencies both improved
      mUPDRS scores compared to no stimulation and did not differ in effect.

PMID- 22592375
TI  - Can we rule out a spinal arteriovenous fistula using only MRI? Yes, we can.

PMID- 22592374
TI  - Risk of fractures in patients with multiple sclerosis: a population-based cohort
      study.
AB  - OBJECTIVE: To examine the risk of fracture in patients with multiple sclerosis
      (MS) compared with population-based controls. METHODS: A population-based cohort
      study was performed in the Dutch PHARMO Record Linkage System (1998-2008).
      Patients with MS (n = 2,415) were matched by year of birth, sex, and practice to
      up to 6 patients without MS (controls). We used Cox proportional hazards models
      to estimate the hazard ratio (HR) of fracture in MS. Time-dependent adjustments
      were made for age, history of disease, and drug use. RESULTS: During follow-up,
      there were 59 fractures among patients with MS (2.4%) and 227 fractures among
      controls (1.8%). Patients with MS had a 1.7-fold increased risk of osteoporotic
      fracture (HR 1.73 [95% confidence interval (CI) 1.18-2.53]) and a 4-fold
      increased risk of hip fracture (HR 4.08 [95% CI 2.21-7.56]). The risk of
      osteoporotic fracture was significantly greater for patients with MS who had been
      prescribed antidepressants (HR 3.25 [95% CI 1.77-5.97]) or hypnotics/anxiolytics
      (HR 3.40 [95% CI 2.06-5.63]) in the previous 6 months, compared with controls.
      CONCLUSIONS: Increased awareness of the risk of hip fracture is warranted in
      patients with MS, especially in those who have recently been prescribed
      antidepressants or hypnotics/anxiolytics.

PMID- 22592376
TI  - Rising incidence of multiple sclerosis in females associated with urbanization.
AB  - OBJECTIVE: To design and perform a case-control study of multiple sclerosis (MS)
      in Crete, an island of 0.6 million people, that has experienced profound
      socioeconomic changes in recent decades. METHODS: All MS cases occurring on Crete
      from 1980 to 2008 were ascertained. To search for putative risk factors, a
      structured questionnaire of 71 variables was employed, with patients with MS (n =
      657) being compared to random controls (n = 593) matched for age, gender, and
      current place of residence. RESULTS: MS incidence rose markedly on Crete over the
      past 3 decades. This increase was associated with a major shift in MS
      distribution among genders (1980: F/M = 0.9; 2008: F/M = 2.1), with females
      living in towns or having relocated at a young age from the countryside to urban
      centers being mainly affected. In rural Crete, MS showed lesser increases and
      gender preference. Of the major changes that accompanied urbanization, smoking
      among women with MS increased dramatically, while imported pasteurized cow milk
      virtually replaced fresh goat milk produced locally. Compared to controls, female
      patients with MS more often used contraceptives and were older at first
      childbirth. Besides smoking, alcohol drinking and vitamin intake was more common
      among female patients with MS. Also, the distribution of childhood diseases and
      chronic medical conditions differed significantly between patients with MS and
      controls. CONCLUSIONS: MS incidence rose markedly over 3 decades in a genetically
      stable population in tandem with a transition from rural to urban living, thus
      possibly implicating environmental factors introduced by urbanization.

PMID- 22592378
TI  - Improvement of 3D protein models using multiple templates guided by single
      template model quality assessment.
AB  - MOTIVATION: Modelling the 3D structures of proteins can often be enhanced if more
      than one fold template is used during the modelling process. However, in many
      cases, this may also result in poorer model quality for a given target or
      alignment method. There is a need for modelling protocols that can both
      consistently and significantly improve 3D models and provide an indication of
      when models might not benefit from the use of multiple target-template
      alignments. Here, we investigate the use of both global and local model quality
      prediction scores produced by ModFOLDclust2, to improve the selection of target
      template alignments for the construction of multiple-template models.
      Additionally, we evaluate clustering the resulting population of multi- and
      single-template models for the improvement of our IntFOLD-TS tertiary structure
      prediction method. RESULTS: We find that using accurate local model quality
      scores to guide alignment selection is the most consistent way to significantly
      improve models for each of the sequence to structure alignment methods tested. In
      addition, using accurate global model quality for re-ranking alignments, prior to
      selection, further improves the majority of multi-template modelling methods
      tested. Furthermore, subsequent clustering of the resulting population of
      multiple-template models significantly improves the quality of selected models
      compared with the previous version of our tertiary structure prediction method,
      IntFOLD-TS. AVAILABILITY AND IMPLEMENTATION: Source code and binaries can be
      freely downloaded from http://www.reading.ac.uk/bioinf/downloads/

PMID- 22592377
TI  - In silico identification software (ISIS): a machine learning approach to tandem
      mass spectral identification of lipids.
AB  - MOTIVATION: Liquid chromatography-mass spectrometry-based metabolomics has gained
      importance in the life sciences, yet it is not supported by software tools for
      high throughput identification of metabolites based on their fragmentation
      spectra. An algorithm (ISIS: in silico identification software) and its
      implementation are presented and show great promise in generating in silico
      spectra of lipids for the purpose of structural identification. Instead of using
      chemical reaction rate equations or rules-based fragmentation libraries, the
      algorithm uses machine learning to find accurate bond cleavage rates in a mass
      spectrometer employing collision-induced dissociation tandem mass spectrometry.
      RESULTS: A preliminary test of the algorithm with 45 lipids from a subset of
      lipid classes shows both high sensitivity and specificity.

PMID- 22592379
TI  - OSA: a fast and accurate alignment tool for RNA-Seq.
AB  - Accurately mapping RNA-Seq reads to the reference genome is a critical step for
      performing downstream analysis such as transcript assembly, isoform detection and
      quantification. Many tools have been developed; however, given the huge size of
      the next generation sequencing datasets and the complexity of the transcriptome,
      RNA-Seq read mapping remains a challenge with the ever-increasing amount of data.
      We develop Omicsoft sequence aligner (OSA), a fast and accurate alignment tool
      for RNA-Seq data. Benchmarked with existing methods, OSA improves mapping speed 4
      10-fold with better sensitivity and less false positives. AVAILABILITY: OSA can
      be downloaded from http://omicsoft.com/osa. It is free to academic users. OSA has
      been tested extensively on Linux, Mac OS X and Windows platforms.

PMID- 22592380
TI  - MotifSuite: workflow for probabilistic motif detection and assessment.
AB  - MOTIVATION: Probabilistic motif detection requires a multi-step approach going
      from the actual de novo regulatory motif finding up to a tedious assessment of
      the predicted motifs. MotifSuite, a user-friendly web interface streamlines this
      analysis flow. Its core consists of two post-processing procedures that allow
      prioritizing the motif detection output. The tools offered by MotifSuite are
      built around the well-established motif detection tool MotifSampler and can also
      be used in combination with any other probabilistic motif detection tool.
      Elaborate guidelines on each of its applications have been provided.
      AVAILABILITY: http://homes.esat.kuleuven.be/bioi_marchal/MotifSuite/Index.htm

PMID- 22592381
TI  - IRView: a database and viewer for protein interacting regions.
AB  - Protein-protein interactions (PPIs) are mediated through specific regions on
      proteins. Some proteins have two or more protein interacting regions (IRs) and
      some IRs are competitively used for interactions with different proteins. IRView
      currently contains data for 3417 IRs in human and mouse proteins. The data were
      obtained from different sources and combined with annotated region data from
      InterPro. Information on non-synonymous single nucleotide polymorphism sites and
      variable regions owing to alternative mRNA splicing is also included. The IRView
      web interface displays all IR data, including user-uploaded data, on reference
      sequences so that the positional relationship between IRs can be easily
      understood. IRView should be useful for analyzing underlying relationships
      between the proteins behind the PPI networks. AVAILABILITY: IRView is publicly
      available on the web at http://ir.hgc.jp/

PMID- 22592382
TI  - Identifying mechanistic similarities in drug responses.
AB  - MOTIVATION: In early drug development, it would be beneficial to be able to
      identify those dynamic patterns of gene response that indicate that drugs
      targeting a particular gene will be likely or not to elicit the desired response.
      One approach would be to quantitate the degree of similarity between the
      responses that cells show when exposed to drugs, so that consistencies in the
      regulation of cellular response processes that produce success or failure can be
      more readily identified. RESULTS: We track drug response using fluorescent
      proteins as transcription activity reporters. Our basic assumption is that drugs
      inducing very similar alteration in transcriptional regulation will produce
      similar temporal trajectories on many of the reporter proteins and hence be
      identified as having similarities in their mechanisms of action (MOA). The main
      body of this work is devoted to characterizing similarity in temporal
      trajectories/signals. To do so, we must first identify the key points that
      determine mechanistic similarity between two drug responses. Directly comparing
      points on the two signals is unrealistic, as it cannot handle delays and speed
      variations on the time axis. Hence, to capture the similarities between reporter
      responses, we develop an alignment algorithm that is robust to noise, time delays
      and is able to find all the contiguous parts of signals centered about a core
      alignment (reflecting a core mechanism in drug response). Applying the proposed
      algorithm to a range of real drug experiments shows that the result agrees well
      with the prior drug MOA knowledge. AVAILABILITY: The R code for the RLCSS
      algorithm is available at http://gsp.tamu.edu/Publications/supplementary/zhao12a.

PMID- 22592383
TI  - Fast computation for genome-wide association studies using boosted one-step
      statistics.
AB  - MOTIVATION: Statistical analyses of genome-wide association studies (GWAS)
      require fitting large numbers of very similar regression models, each with low
      statistical power. Taking advantage of repeated observations or correlated
      phenotypes can increase this statistical power, but fitting the more complicated
      models required can make computation impractical. RESULTS: In this article, we
      present simple methods that capitalize on the structure inherent in GWAS studies
      to dramatically speed up computation for a wide variety of problems, with a
      special focus on methods for correlated phenotypes. AVAILABILITY: The R package
      'boss' is available on the Comprehensive R Archive Network (CRAN) at
      http://cran.r-project.org/web/packages/boss/

PMID- 22592385
TI  - Theoretical study of the interaction between 5-methylcytosine and acrylamide.
AB  - The hydrogen-bonded complexes between 5-methylcytosine and acrylamide have been
      investigated using the density function theory (DFT) method. Five stable
      complexes have been found with no imaginary frequencies. Complex C3 is the most
      stable one with interaction energies of -69.01 kJ mol(-1) corrected for basis set
      superposition error (BSSE). The charge change in the process of these complexes
      formation has also been examined. The atoms in molecules (AIM) theory and natural
      bond orbital (NBO) method have been performed to investigate the hydrogen bonds
      involved in all the complexes. The electron density and its corresponding
      Laplacian at the bond and ring critical points have been analyzed. In C3 complex,
      there is the largest stabilization energy (18.17 kJ mol(-1)) between N11-H12
      antibonding orbital and lone electron pair of O17. It can be seen that the
      hydrogen bonds play a crucial role in the stability of all the complexes between
      5-methylcytosine and acrylamide. The theoretical results could provide helpful
      information for other researchers in further work.

PMID- 22592387
TI  - A novel quantitative approach to concept analysis: the internomological network.
AB  - BACKGROUND: When a construct such as patients' "transition to self-management" of
      chronic illness is studied by researchers across multiple disciplines, the
      meaning of key terms can become confused. This results from inherent problems in
      language where a term can have multiple meanings (polysemy) and different words
      can mean the same thing (synonymy). OBJECTIVES: The aim of this study was to test
      a novel quantitative method for clarifying the meaning of constructs by examining
      the similarity of published contexts in which they are used. METHODS: Published
      terms related to the concept transition to self-management of chronic illness
      were analyzed using the internomological network (INN), a type of latent semantic
      analysis performed to calculate the mathematical relationships between constructs
      based on the contexts in which researchers use each term. This novel approach was
      tested by comparing results with those from concept analysis, a best-practice
      qualitative approach to clarifying meanings of terms. By comparing results of the
      2 methods, the best synonyms of transition to self-management, as well as key
      antecedent, attribute, and consequence terms, were identified. RESULTS: Results
      from INN analysis were consistent with those from concept analysis. The potential
      synonyms self-management, transition, and adaptation had the greatest utility.
      Adaptation was the clearest overall synonym but had lower cross-disciplinary use.
      The terms coping and readiness had more circumscribed meanings. The INN analysis
      confirmed key features of transition to self-management and suggested related
      concepts not found by the previous review. DISCUSSION: The INN analysis is a
      promising novel methodology that allows researchers to quantify the semantic
      relationships between constructs. The method works across disciplinary boundaries
      and may help to integrate the diverse literature on self-management of chronic
      illness.

PMID- 22592386
TI  - Iterative experimental and virtual high-throughput screening identifies
      metabotropic glutamate receptor subtype 4 positive allosteric modulators.
AB  - Activation of metabotropic glutamate receptor subtype 4 has been shown to be
      efficacious in rodent models of Parkinson's disease. Artificial neural networks
      were trained based on a recently reported high throughput screen which identified
      434 positive allosteric modulators of metabotropic glutamate receptor subtype 4
      out of a set of approximately 155,000 compounds. A jury system containing three
      artificial neural networks achieved a theoretical enrichment of 15.4 when
      selecting the top 2 % compounds of an independent test dataset. The model was
      used to screen an external commercial database of approximately 450,000 drug-like
      compounds. 1,100 predicted active small molecules were tested experimentally
      using two distinct assays of mGlu(4) activity. This experiment yielded 67
      positive allosteric modulators of metabotropic glutamate receptor subtype 4 that
      confirmed in both experimental systems. Compared to the 0.3 % active compounds in
      the primary screen, this constituted an enrichment of 22 fold.

PMID- 22592388
TI  - Daytime physical activity levels in school-age children with and without asthma.
AB  - BACKGROUND: Physical activity (PA) is a significant predictor of health outcomes
      in children with and without chronic conditions. Few researchers have used
      actigraphy as an objective measure of PA during the child's normal daily
      routines, and the findings have been inconsistent. It is unclear if asthma can
      contribute to low PA levels. OBJECTIVES: The aim of this study was to compare
      daytime PA levels in children with and without asthma and examine the
      relationships among asthma, PA, body mass index (BMI), and child reports of
      symptoms. METHODS: Physical activity as measured by actigraphy and self-report
      symptoms of coughing, wheezing, chest tightness, perceived tiredness, sleepiness,
      and alertness were obtained in 54 children aged 9-11 years with and without
      asthma for 7 consecutive days. Activity variables derived from actigraphy
      included (a) mean daytime activity level; (b) peak daytime activity level; and
      (c) time duration spent in sedentary, light, moderate, vigorous, and total
      moderate plus vigorous PA (MVPA). RESULTS: Children with and without asthma did
      not differ on BMI or activity levels. Children with asthma reported more activity
      limitations due to breathing problems than children without asthma (p < .01). In
      multivariate analyses, asthma predicted reduced mean, peak, and total time spent
      in MVPA level after controlling for gender, BMI, and self-report of symptoms. A
      significant interaction was found between asthma and BMI on mean, peak, and total
      time spent in MVPA. DISCUSSION: The association between asthma and PA is complex
      when the child's BMI is considered. Results suggest that reduced PAs with respect
      to respiratory symptom severity, childhood obesity, and functional impairment are
      important areas for future studies.

PMID- 22592389
TI  - An electronic fall prevention toolkit: effect on documentation quality.
AB  - BACKGROUND: Nursing documentation is the record of care that is planned and given
      to patients, yet it is often missing or incomplete. A study of translating
      results from nurses' assessments of fall risk into tailored interventions using
      health information technology was used to examine nursing documentation of risk
      assessment, plans to manage those risks, and interventions to prevent falls.
      OBJECTIVE: The aim of this study was to evaluate the effectiveness of an
      electronic fall prevention toolkit for promoting documentation of fall risk
      status and planned and completed fall prevention interventions. METHODS: Nursing
      documentation related to fall risk and prevention was reviewed in 30% of randomly
      selected medical records for patients on the eight study units (four intervention
      units; 5,267 patients) and four usual care units (5,116 patients) during three
      separate study visits. RESULTS: Patients on the intervention units were more
      likely to have fall risk documented (89% vs. 64%, p < .0001). There were
      significantly more comprehensive plans of care for the patients on the
      interventions documented, although no differences were found related to
      documentation of completed interventions compared with usual care unit patient
      records. DISCUSSION: The documentation of fall risk status and planned
      interventions tailored to patient-specific areas of risk was significantly better
      on the intervention units that used the fall prevention toolkit as compared with
      usual care units. Improved documentation quality did not extend to the
      documentation of completed interventions.

PMID- 22592390
TI  - Postpartum health promotion interventions: a systematic review.
AB  - BACKGROUND: The postpartum period is a time of significant transition when women
      may discontinue positive health behaviors adopted during pregnancy. Little is
      known about the effectiveness of health promotion interventions targeting
      postpartum women. OBJECTIVE: The aim of this study was to synthesize the
      published evidence from randomized controlled trials conducted in the United
      States on the effectiveness of interventions promoting maternal health in the
      first year after childbirth. METHODS: Studies conducted in the United States and
      published from 1999 through May 2011 were identified in MEDLINE, CINAHL
      (Cumulative Index to Nursing and Allied Health Literature), and PsycINFO and
      reviewed. RESULTS: Eleven studies were identified measuring health promotion
      behaviors as an outcome. Nine of the 11 targeted at-risk groups. Methodological
      problems included incomplete description of the intervention, steps taken to
      ensure representativeness of the sample, and identification and control of
      potential confounders. Diverse aspects of health promotion were addressed, the
      length of participant involvement differed, and the effectiveness of the
      interventions varied. DISCUSSION: Further research is needed to design
      interventions focused on promoting health in the general population of postpartum
      mothers.

PMID- 22592391
TI  - Using machine learning classifiers to assist healthcare-related decisions:
      classification of electronic patient records.
AB  - Surveillance Levels (SLs) are categories for medical patients (used in Brazil)
      that represent different types of medical recommendations. SLs are defined
      according to risk factors and the medical and developmental history of patients.
      Each SL is associated with specific educational and clinical measures. The
      objective of the present paper was to verify computer-aided, automatic assignment
      of SLs. The present paper proposes a computer-aided approach for automatic
      recommendation of SLs. The approach is based on the classification of information
      from patient electronic records. For this purpose, a software architecture
      composed of three layers was developed. The architecture is formed by a
      classification layer that includes a linguistic module and machine learning
      classification modules. The classification layer allows for the use of different
      classification methods, including the use of preprocessed, normalized language
      data drawn from the linguistic module. We report the verification and validation
      of the software architecture in a Brazilian pediatric healthcare institution. The
      results indicate that selection of attributes can have a great effect on the
      performance of the system. Nonetheless, our automatic recommendation of
      surveillance level can still benefit from improvements in processing procedures
      when the linguistic module is applied prior to classification. Results from our
      efforts can be applied to different types of medical systems. The results of
      systems supported by the framework presented in this paper may be used by
      healthcare and governmental institutions to improve healthcare services in terms
      of establishing preventive measures and alerting authorities about the
      possibility of an epidemic.

PMID- 22592392
TI  - Soft-mode-driven lattice instabilities in Cs2HgCl4 crystal: phenomenological
      treatment and far-infrared spectroscopy of the structurally modulated phases.
AB  - This paper reports a comprehensive phenomenological description and experimental
      infrared (IR) investigations of the soft-mode-driven lattice instabilities into
      various commensurately and incommensurately modulated phases of Cs(2)HgCl(4)
      crystals. Our theoretical analysis shows that the lattice instabilities along the
      a and c crystallographic directions are related to low-frequency transverse
      optical (TO) phonon branches of Sigma(2) and Lambda(3) symmetry, respectively,
      which merge together in the center of the Brillouin zone at the point of B(3g)
      symmetry. As the temperature decreases both branches fall down, leading first to
      the direct condensation of the soft TO Sigma(2) mode in the symmetric Sigma
      direction (k is parallel to a*). On the other hand, coupling of the TO and
      transverse acoustic (TA) modes of Lambda(3) symmetry causes, at somewhat lower
      temperatures, a series of frozen modulated commensurate and incommensurate states
      developing along the symmetric Lambda direction (k is parallel to c*). Polarized
      far-infrared (FIR) reflectivity spectra (15-600 cm(-1)) of Cs(2)HgCl(4) crystals
      were measured in a broad temperature region, 10-297 K. Despite a rich sequence of
      structurally modulated phases existing above 163 K we observed rather moderate
      temperature evolution of IR spectra where only a few new modes of different
      polarizations have been activated. However, the commensurately modulated phases
      occurring below 163 K made an essential impact on the spectra of all three
      polarizations. The process of activation of both the Raman- and the IR-active
      phonons in the structurally modulated phases is subjected to the phenomenological
      analysis.

PMID- 22592393
TI  - Energy expenditure before and after Roux-en-Y gastric bypass.
AB  - BACKGROUND: Weight loss may decrease the energy expenditure (EE) because of
      changes in body composition (BC). The reduction in EE may contribute, in part, to
      weight regain. Experimental studies in animals indicate that Roux-en-Y Gastric
      Bypass (RYGB) increases the resting metabolic rate (RMR) when adjusted for body
      weight (BW). Thus, the aim of this study was to assess the clinical effects of
      RYGB on EE in patients who have undergone RYGB. METHODS: The study was
      prospective and included 46 RYGB patients whose RMR was assessed prior to and at
      least 6 months post-surgery by indirect calorimetry. BW and BC were measured at
      these same time points using bioelectric impedance. RMR was adjusted for changes
      in BW, i.e., kilocalories per kilogram. Statistical tests were used to analyze
      the results. RESULTS: The BW-adjusted RMR (kilocalories per kilogram) increased
      post-RYGB by 17.66 % (p < 0.0001). RMR adjusted for BW was negatively correlated
      to the total percentage of body fat preoperatively (r = -0.30729, p = 0.0378) and
      postoperatively (r = -0.46731, p = 0.0011) and was positively correlated to the
      fat-free mass percentage (%FFM) both preoperatively and postoperatively.
      Furthermore, BW-adjusted RMR and %FFM were positively correlated to percent
      excess weight loss (r = 0.55398, p < 0.0001 and r = 0.31677, p = 0.0283,
      respectively). CONCLUSIONS: Weight loss following RYGB is associated with an
      increase in BW-adjusted RMR and with %FFM. An increase in energy expenditure post
      RYGB may be responsible, in part, for successful long-term weight loss of the
      RYGB procedure.

PMID- 22592394
TI  - Major depressive disorder, panic disorder, and post-traumatic stress disorder in
      Korean subway drivers.
AB  - PURPOSE: The purposes of this study are to investigate the prevalence of major
      depressive disorder, panic disorder, and post-traumatic stress disorder (PTSD) in
      Korean subway drivers, and find the association between these disorders and the
      drivers' person-under-train (PUT) experiences. METHODS: A total of 826 subway
      drivers who participated in a cross-sectional work and health survey were
      included for this study. The Korean version of the Composite International
      Diagnostic Interview 2.1 was applied to assess major depressive disorder, panic
      disorder, and PTSD. The date of PUT, whether victim died, and how many PUTs the
      drivers experienced were asked using a structured questionnaire. RESULTS: The
      standardized prevalence ratios (SPRs) for lifetime prevalence of panic disorder
      and PTSD in subway drivers were 13.3 (95 % confidence interval [CI] 6.6-22.4) and
      2.1 (95 % CI 1.1-3.4), respectively. In lifetime prevalence, after adjusting for
      age, education, income, and working career, the drivers who experienced PUT had
      significantly higher risks for panic disorder (odds ratio [OR] = 4.2, 95 % CI 1.2
      16.6) and PTSD (OR = 4.4, 95 % CI 1.3-16.4). In 1-year prevalence, the drivers
      who experienced PUT had a significantly higher risk for PTSD (OR = 11.7, 95 % CI
      1.9-225.8). There was no significant value of SPR and OR in major depressive
      disorder. CONCLUSIONS: This study suggests that Korean subway drivers are at
      higher risk for panic disorder and PTSD compared to the general population, and
      PUT experience is associated with panic disorder and PTSD. Drivers who have
      experienced PUT should be treated quickly, sympathetically, and sensitively by a
      psychological professional and their colleagues, so they can return to work soon.

PMID- 22592395
TI  - Total synthesis of (-)-dysiherbaine.
AB  - The enantioselective synthesis of (-)-dysiherbaine (1) has been established with
      efficiency via a unique synthetic strategy involving the desymmetrization of 2
      substituted glycerol to install a quaternary chiral carbon, which induces further
      stereochemistry in the bicyclic perhydrofuropyran through mercuriocyclization and
      epoxidation.

PMID- 22592397
TI  - [Endothelial corneal dystrophies (CD) - diagnosis and therapy].
AB  - Clinical, histological, and genetic definitions of the four endothelial corneal
      dystrophies (CD) are presented. Of these, Fuchs endothelial CD is one of the most
      common corneal dystrophies in Europe and North America. Beside bullous
      keratopathy, Fuchs CD represents the most frequent indication for posterior
      lamellar keratoplasty that is currently termed "Descemet stripping endothelial
      keratoplasty" or abbreviated, "DSEK". A comparison of the advantages and
      disadvantages of DSEK against the established Excimer laser-assisted penetrating
      keratoplasty is given. The often simultaneous occurrence of Fuchs CD and cataract
      should be treated by phacoemulsification and implantation of a posterior chamber
      lens before the keratoplasty. There are many comparative studies concerning the
      different surgical techniques to evaluate their intra- and postoperative
      advantages and results. Many years will be necessary before we can get a
      scientific and definitive assessment.

PMID- 22592398
TI  - Measuring of the maximum fat lesion ratio.

PMID- 22592399
TI  - Cystoid macular edema induced by nab-paclitaxel.
AB  - Cystoid macular edema (CME) is a rare complication of taxane-based chemotherapy.
      We encountered a patient who developed CME during treatment with nab-paclitaxel
      for metastatic breast cancer. Early detection of this disease enables
      continuation of appropriate treatment without reducing the quality of life for
      patients with end-stage disease. Physicians should be aware of this potential
      adverse effect, and should make changes to the treatment of patients as soon as
      possible. 

PMID- 22592400
TI  - Sulfoxide-mediated Umpolung of alkali halide salts.
AB  - A new protocol for the direct two-electron oxidative Umpolung of alkali halide
      salts is reported. This procedure, relying on the use of a commercially available
      sulfoxide as the oxidant, allows the electrophilic halogenation of carbonyl
      compounds as well as halolactonisation reactions to proceed from the
      corresponding sodium salts, at room temperature and under mild conditions.

PMID- 22592401
TI  - Upregulation of thrombospondin-1 expression by leptin in vascular smooth muscle
      cells via JAK2- and MAPK-dependent pathways.
AB  - Hyperleptinemia, characteristic of diabetes and a hallmark feature of human
      obesity, contributes to the increased risk of atherosclerotic complications.
      However, molecular mechanisms mediating leptin-induced atherogenesis and gene
      expression in vascular cells remain incompletely understood. Accumulating
      evidence documents a critical role of a potent antiangiogenic and proatherogenic
      matricellular protein, thrombospondin-1 (TSP-1), in atherosclerosis. Although
      previous studies reported elevated TSP-1 levels in both diabetic and obese
      patients and rodent models, there is no direct information on TSP-1 expression in
      vascular cells in response to leptin. In the present study, we show that leptin
      upregulates TSP-1 expression in cultured human aortic smooth muscle cells (HASMC)
      in vitro, and this increase occurs at the level of transcription, revealed by
      mRNA stability and TSP-1 promoter-reporter assays. Utilizing specific
      pharmacological inhibitors and siRNA approaches, we demonstrate that upregulation
      of TSP-1 expression by leptin is mediated by JAK2/ERK/JNK-dependent mechanisms.
      Furthermore, we report that while ERK and JNK are required for both the
      constitutive and leptin-induced expression of TSP-1, JAK-2 appears to be
      specifically involved in leptin-mediated TSP-1 upregulation. Finally, we found
      that increased HASMC migration and proliferation in response to leptin is
      significantly inhibited by a TSP-1 blocking antibody, thereby revealing the
      physiological significance of leptin-TSP-1 crosstalk. Taken together, these
      findings demonstrate, for the first time, that leptin has a direct regulatory
      effect on TSP-1 expression in HASMCs, underscoring a novel role of TSP-1 in
      hyperleptinemia-induced atherosclerotic complications.

PMID- 22592402
TI  - Structural and functional evaluation of branched myofibers lacking intermediate
      filaments.
AB  - Intermediate filaments (IFs), composed of desmin and keratins, link myofibrils to
      each other and to the sarcolemma in skeletal muscle. Fast-twitch muscle of mice
      lacking the IF proteins, desmin and keratin 19 (K19), showed reduced specific
      force and increased susceptibility to injury in earlier studies. Here we tested
      the hypothesis that the number of malformed myofibers in mice lacking desmin
      (Des(-/-)), keratin 19 (K19(-/-)), or both IF proteins (double knockout, DKO) is
      increased and is coincident with altered excitation-contraction (EC) coupling
      Ca(2+) kinetics, as reported for mdx mice. We quantified the number of branched
      myofibers, characterized their organization with confocal and electron microscopy
      (EM), and compared the Ca(2+) kinetics of EC coupling in flexor digitorum brevis
      myofibers from adult Des(-/-), K19(-/-), or DKO mice and compared them to age
      matched wild type (WT) and mdx myofibers. Consistent with our previous findings,
      9.9% of mdx myofibers had visible malformations. Des(-/-) myofibers had more
      malformations (4.7%) than K19(-/-) (0.9%) or DKO (1.3%) myofibers. Confocal and
      EM imaging revealed no obvious changes in sarcomere misalignment at the branch
      points, and the neuromuscular junctions in the mutant mice, while more variably
      located, were limited to one per myofiber. Global, electrically evoked Ca(2+)
      signals showed a decrease in the rate of Ca(2+) uptake (decay rate) into the
      sarcoplasmic reticulum after Ca(2+) release, with the most profound effect in
      branched DKO myofibers (44% increase in uptake relative to WT). Although branched
      DKO myofibers showed significantly faster rates of Ca(2+) clearance, the milder
      branching phenotype observed in DKO muscle suggests that the absence of K19
      corrects the defect created by the absence of desmin alone. Thus, there are
      complex roles for desmin-based and K19-based IFs in skeletal muscle, with the
      null and DKO mutations having different effects on Ca(2+) reuptake and myofiber
      branching.

PMID- 22592403
TI  - Rel A/p65 is required for cytokine-induced myotube atrophy.
AB  - Muscle atrophy can be triggered by systemic illnesses that are associated with
      elevated proinflammatory/catabolic cytokines, which, in turn, are thought to
      contribute to muscle wasting. In this study, we found that the prototypical NF
      kappaB transcription factor, Rel A (p65), is required for NF-kappaB activation in
      C2C12 and L6 myotubes due to treatment with exogenous TNF-alpha, IL-1alpha, IL
      1beta, TNF-related weak inducer of apoptosis, but not IL-6. All five cytokines
      induced atrophy in C2C12 myotubes, and inhibition of p65 reversed atrophy due to
      TNF-alpha, IL-1alpha, IL-1beta, TNF-related weak inducer of apoptosis, but not IL
      6 treatment. p65 was also required for TNF-alpha-induced increase in atrophy and
      inflammatory gene expression. TNF-alpha- and IL-1beta-treated myotubes increased
      IL-6 protein expression, but use of an IL-6 blocking antibody showed that the IL
      6 production did not contribute to atrophy. These data show that p65 is a
      required transcription factor mediating the catabolic effects of four different
      cytokines in cultured myotubes, but IL-6 works by a different mechanism.

PMID- 22592404
TI  - Cell-autonomous regulation of fast troponin T pre-mRNA alternative splicing in
      response to mechanical stretch.
AB  - How mechanochemical signals induced by the amount of weight borne by the skeletal
      musculature are translated into modifications to muscle sarcomeres is poorly
      understood. Our laboratory recently demonstrated that, in response to
      experimentally induced increases in the weight load borne by a rat, alternative
      splicing of the fast skeletal muscle troponin T (Tnnt3) pre-mRNA in gastrocnemius
      was adjusted in a correlated fashion with the amount of added weight. (Schilder
      RJ, Kimball SR, Marden JH, Jefferson LS. J Exp Biol 214: 1523-1532, 2011). Thus
      muscle load is perceived quantitatively by the body, and mechanisms that sense it
      appear to control processes that generate muscle sarcomere composition
      plasticity, such as alternative pre-mRNA splicing. Here we demonstrate how
      mechanical stretch (see earlier comment) of C2C12 muscle cells in culture results
      in changes to Tnnt3 pre-mRNA alternative splicing that are qualitatively similar
      to those observed in response to added weight in rats. Moreover, inhibition of
      Akt signaling, but not that of ERK1/2, prevents the stretch-induced effect on
      Tnnt3 pre-mRNA alternative splicing. These findings suggest that effects of
      muscle load on Tnnt3 pre-mRNA alternative splicing are controlled by a cell
      autonomous mechanism, rather than systemically. They also indicate that, in
      addition to its regulatory role in protein synthesis and muscle mass plasticity,
      Akt signaling may regulate muscle sarcomere composition by modulating alternative
      splicing events in response to load. Manipulation of Tnnt3 pre-mRNA alternative
      splicing by mechanical stretch of cells in culture provides a model to
      investigate the biology of weight sensing by skeletal muscles and facilitates
      identification of mechanisms through which skeletal muscles match their
      performance and experienced load.

PMID- 22592405
TI  - Physical and functional interaction between the ID1 and p65 for activation of NF
      kappaB.
AB  - Inhibitor of differentiation or DNA binding-1 (ID1) is an important helix-loop
      helix (HLH) transcription factor involved in diverse biological functions
      including cell differentiation, proliferation, apoptosis, and senescence.
      Recently, it was reported that ID1 can activate the NF-kappaB signaling pathway
      in a variety of cancer cells and a T cell line, but the mechanisms involved in
      ID1-mediated transactivation of NF-kappaB are not clear. In this study, we
      demonstrate by both in vitro pull-down assays and a cell-based in vivo two-hybrid
      system that ID1-mediated NF-kappaB activation is due to its physical interaction
      with p65. We have identified that the transcriptional activation domain (TAD) in
      p65 and the HLH domain in ID1 are vital for their interaction. Interestingly, a
      single site mutation (Leu76) in the HLH domain of ID1 protein drastically
      decreased its ability to bind with p65. Using a dual-luciferase assay, we
      demonstrated that the interaction between ID1 and p65 modulates activation of the
      NF-kappaB signaling pathway in vivo. In addition, we demonstrated that, by
      affecting the nuclear translocation of p65, ID1 is essential in regulating TNF
      alpha-induced p65 recruitment to its downstream target, the cellular inhibitor of
      apoptosis protein 2 (cIAP2) promoter.

PMID- 22592406
TI  - Acid-sensing ion channels contribute to the increase in vesicular release from SH
      SY5Y cells stimulated by extracellular protons.
AB  - Acid-sensing ion channels (ASICs) have been reported to play a role in the
      neuronal dopamine pathway, but the exact role in neurotransmitter release remains
      elusive. Human neuroblastoma SH-SY5Y is a dopaminergic neuronal cell line, which
      can release monoamine neurotransmitters. In this study, the expression of ASICs
      was identified in SH-SY5Y cells to further explore the role of ASICs in vesicular
      release stimulated by acid. We gathered evidence that ASICs could be detected in
      SH-SY5Y cells. In whole cell patch-clamp recording, a rapid decrease in
      extracellular pH evoked inward currents, which were reversibly inhibited by 100
      MUM amiloride. The currents were pH dependent, with a pH of half-maximal
      activation (pH(0.5)) of 6.01 +/- 0.04. Furthermore, in calcium imaging and FM 1
      43 dye labeling, it was shown that extracellular protons increased intracellular
      calcium levels and vesicular release in SH-SY5Y cells, which was attenuated by
      PcTx1 and amiloride. Interestingly, N-type calcium channel blockers inhibited the
      vesicular release induced by acidification. In conclusion, ASICs are functionally
      expressed in SH-SY5Y cells and involved in vesicular release stimulated by
      acidification. N-type calcium channels may be involved in the increase in
      vesicular release induced by acid. Our results provide a preliminary study on
      ASICs in SH-SY5Y cells and neurotransmitter release, which helps to further
      investigate the relationship between ASICs and dopaminergic neurons.

PMID- 22592409
TI  - A new concept of diffuse (low-grade) glioma surgery.
AB  - Preservation and even improvement of the quality of life is currently a priority
      in surgery for gliomas, in addition to the optimization of the extent of
      resection with significant increase of the overall survival. In this setting, the
      goal of the present review is to revisit technical aspects of glioma surgery in
      the lights of new concepts both in the fields of neurooncology and cognitive
      neurosciences, which recently emerged from translational researches - with
      special emphasis on diffuse low grade gliomas.Firstly, the vascularisation
      (arteries and veins) has to be more systematically spared, by performing subpial
      dissection and by limiting the use of coagulation within the brain. Secondly,
      individual cortical as well as subcortical mapping must be more regularly
      considered, with the aim of better understanding and preserving the white matter
      pathways underlying the functional connectivity - even in presumed "non-eloquent
      areas", to perform "supra-complete" resection.Therefore, brain surgeons should
      change their state of mind, in order to operate the nervous system involved by a
      chronic tumoral disease (and no more by operating a tumor mass within the brain).
      In other words, the neurosurgeon should see first the brain, and not the glioma,
      to adapt his surgical procedure to the three-dimensional anatomo-functional
      organization of each patient. It implies that brain surgeon must change his
      technique within the central nervous system, which has to be different from the
      surgical technique outside the brain. This perspective seems to represent the
      best way to build a modern and personalized "functional surgical neurooncology".

PMID- 22592408
TI  - Pituitary adenylate cyclase-activating peptide enhances electrical coupling in
      the mouse adrenal medulla.
AB  - Neuroendocrine adrenal medullary chromaffin cells receive synaptic excitation
      through the sympathetic splanchnic nerve to elicit catecholamine release into the
      circulation. Under basal sympathetic tone, splanchnic-released acetylcholine
      evokes chromaffin cells to fire action potentials, leading to synchronous phasic
      catecholamine release. Under elevated splanchnic firing, experienced under the
      sympathoadrenal stress response, chromaffin cells undergo desensitization to
      cholinergic excitation. Yet, stress evokes a persistent and elevated adrenal
      catecholamine release. This sustained stress-evoked release has been shown to
      depend on splanchnic release of a peptide transmitter, pituitary adenylate
      cyclase-activating peptide (PACAP). PACAP stimulates catecholamine release
      through a PKC-dependent pathway that is mechanistically independent of
      cholinergic excitation. Moreover, it has also been reported that shorter term
      phospho-regulation of existing gap junction channels acts to increase junctional
      conductance. In this study, we test if PACAP-mediated excitation upregulates cell
      cell electrical coupling to enhance chromaffin cell excitability. We utilize
      electrophysiological recordings conducted in adrenal tissue slices to measure the
      effects of PACAP stimulation on cell coupling. We report that PACAP excitation
      increases electrical coupling and the spread of electrical excitation between
      adrenal chromaffin cells. Thus PACAP acts not only as a secretagogue but also
      evokes an electrical remodeling of the medulla, presumably to adapt to the
      organism's needs during acute sympathetic stress.

PMID- 22592407
TI  - Polyamines regulate intestinal epithelial restitution through TRPC1-mediated Ca2+
      signaling by differentially modulating STIM1 and STIM2.
AB  - Early epithelial restitution occurs as a consequence of intestinal epithelial
      cell (IEC) migration after wounding, and its defective regulation is implicated
      in various critical pathological conditions. Polyamines stimulate intestinal
      epithelial restitution, but their exact mechanism remains unclear. Canonical
      transient receptor potential-1 (TRPC1)-mediated Ca(2+) signaling is crucial for
      stimulation of IEC migration after wounding, and induced translocation of stromal
      interaction molecule 1 (STIM1) to the plasma membrane activates TRPC1-mediated
      Ca(2+) influx and thus enhanced restitution. Here, we show that polyamines
      regulate intestinal epithelial restitution through TRPC1-mediated Ca(2+)
      signaling by altering the ratio of STIM1 to STIM2. Increasing cellular polyamines
      by ectopic overexpression of the ornithine decarboxylase (ODC) gene stimulated
      STIM1 but inhibited STIM2 expression, whereas depletion of cellular polyamines by
      inhibiting ODC activity decreased STIM1 but increased STIM2 levels. Induced
      STIM1/TRPC1 association by increasing polyamines enhanced Ca(2+) influx and
      stimulated epithelial restitution, while decreased formation of the STIM1/TRPC1
      complex by polyamine depletion decreased Ca(2+) influx and repressed cell
      migration. Induced STIM1/STIM2 heteromers by polyamine depletion or STIM2
      overexpression suppressed STIM1 membrane translocation and inhibited Ca(2+)
      influx and epithelial restitution. These results indicate that polyamines
      differentially modulate cellular STIM1 and STIM2 levels in IECs, in turn
      controlling TRPC1-mediated Ca(2+) signaling and influencing cell migration after
      wounding.

PMID- 22592410
TI  - Spinal cord injury and its treatment: current management and experimental
      perspectives.
AB  - Clinical management of spinal cord injury (SCI) has significantly improved its
      general prognosis. However, to date, traumatic paraplegia and tetraplegia remain
      incurable, despite massive research efforts. Current management focuses on
      surgical stabilisation of the spine, intensive neurological rehabilitation, and
      the prevention and treatment of acute and chronic complications. Prevention
      remains the most efficient strategy and should be the main focus of public health
      efforts. Nevertheless, major advances in the understanding of the
      pathophysiological mechanisms of SCI open promising new therapeutic perspectives.
      Even if complete recovery remains elusive due to the complexity of spinal cord
      repair, a strategy combining different approaches may result in some degree of
      neurological improvement after SCI. Even slight neurological recovery can have
      high impact on the daily functioning of severely handicapped patients and, thus,
      result in significant improvements in quality of life.The main investigated
      strategies are: [1] initial neuroprotection, in order to decrease secondary
      injury to the spinal cord parenchyma after the initial insult; [2] spinal cord
      repair, in order to bridge the lesion site and reestablish the connection between
      the supraspinal centres and the deafferented cord segment below the lesion; and
      [3] re-training and enhancing plasticity of the central nervous system circuitry
      that was preserved or rebuilt after the injury.Now and in the future, treatment
      strategies that have both a convincing rationale and seen their efficacy
      confirmed reproducibly in the experimental setting must carefully be brought from
      bench to bedside. In order to obtain clinically significant results, their
      introduction into clinical research must be guided by scientific rigour, and
      their coordination must be rationally structured in a long-term perspective.

PMID- 22592411
TI  - Percutaneous biopsy through the foramen ovale for parasellar lesions: surgical
      anatomy, method, and indications.
AB  - Knowledge of the pathological diagnosis before deciding the best strategy for
      treating parasellar lesions is of prime importance, due to the relative high
      morbidity and side-effects of open direct approaches to this region, known to be
      rich in important vasculo-nervous structures. When imaging is not evocative
      enough to ascertain an accurate pathological diagnosis, a percutaneous biopsy
      through the transjugal-transoval route (of Hartel) may be performed to guide the
      therapeutic decision.The chapter is based on the authors' experience in 50
      patients who underwent the procedure over the ten past years. There was no
      mortality and only little (mostly transient) morbidity. Pathological diagnosis
      accuracy of the method revealed good, with a sensitivity of 0.83 and a
      specificity of 1.In the chapter the authors first recall the surgical anatomy
      background from personal laboratory dissections. They then describe the technical
      procedure, as well as the tissue harvesting method. Finally they define
      indications together with the decision-making process.Due to the constraint
      trajectory of the biopsy needle inserted through the Foramen Ovale, accessible
      lesions are only those located in the Meckel trigeminal Cave, the posterior
      sector of the cavernous sinus compartment, and the upper part of the petroclival
      region.The authors advise to perform this percutaneous biopsy method when imaging
      does not provide sufficient evidence of the pathological nature of the lesion,
      for therapeutic decision. Goal is to avoid unnecessary open surgery or
      radiosurgery, also inappropriate chemo-/radio-therapy.

PMID- 22592412
TI  - Percutaneous pedicle screw implantation for refractory low back pain: from manual
      2D to fully robotic intraoperative 2D/3D fluoroscopy.
AB  - Many surgical treatments for chronic low back pain that is refractory to medical
      treatments focus on spine stabilization. One of the main surgical procedures
      consists of placing an interbody cage with bone grafts associated with pedicle
      screws [2, 25, 30]. This technique can be performed using different approaches: a
      large open posterior approach, tubular approaches (minimal open) or
      percutaneously (minimally invasive percutaneous or MIP) [5, 28]. One of the main
      difficulties is to precisely locate the screws into the pedicle avoiding
      especially infero-medial pedicle breaches. This difficulty is even great- er when
      working percutaneously. This paper focuses on percutaneously placed pedicle
      screws (PPS), reports the use of a robotic multi-axis 2D/3D fluoros- copy to
      enhance the accuracy of pedicle screw placement and reviews other strategies and
      results reported in the literature.

PMID- 22592413
TI  - The choroidal fissure: anatomy and surgical implications.
AB  - The choroidal fissure (CF) is an important landmark that allows approaches to the
      deepest aspects of the brain. It is the C-shaped site of attachment of the
      choroid plexus in the lateral ventricles, which runs between fornix and thalamus.
      The thinness and the absence of neural tissue between the ependyma and pia matter
      of this part of the medial wall of the lateral ventricles provides a surgical
      pathway to the third ventricle and perimesencephalic cisterns. A precise
      knowledge of the microsurgical anatomy of the region, particularly vascular
      relationships, is essential to consider surgery through the CF. We decided to
      present the anatomy of the CF in three distinct chapters, corresponding to three
      compartments of the C-shaped structure of the CF. In each compartment - rostral,
      dorsal and caudal - we developed the neurovascular anatomy and then discussed the
      clinical and surgical applications.

PMID- 22592414
TI  - Decompressive craniectomy - operative technique and perioperative care.
AB  - With improvements in neurocritical care advanced measures of treating raised
      intracranial pressure (ICP) are more frequently utilised. Decompressive
      craniectomy is an effective ICP-lowering procedure; however its benefits are
      maximised with optimal surgical technique and perioperative care, as well as by
      paying attention to possible complications. This article focuses on the current
      indications and rationale for decompressive craniectomy, and the surgical
      technique of bifrontal and unilateral decompression. The key surgical points
      include a large craniectomy window and opening of the dura, leaving it unsutured
      or performing a wide non-constricting duroplasty. Perioperative care and possible
      complications are also discussed.

PMID- 22592415
TI  - Management of cortical dysplasia in epilepsy.
AB  - Focal cortical dysplasias (FCD) are increasingly diagnosed as a cause of
      symptomatic focal epilepsy in paediatric and adult patients. Nowadays, focal
      cortical dysplasias are identified as the underlying pathology in up to 25% of
      patients with focal epilepsies. The histological appearance can vary from mild
      architectural disturbances to severe malformation containing atypical cellular
      elements like dysmorphic neurons and Balloon cells. Clinical presentation depends
      on the age at onset of epilepsy, the location and size of the lesion. In most
      patients seizures begin in early childhood and the course of epilepsy is often
      severe and pharmaco-resistant. For the majority of patients, epilepsy surgery is
      the only treatment option in order to become seizure free.In this review an
      overview on the literature of the last ten years is provided, focussing on
      histological appearance and classification, pathogenetic mechanisms and clinical
      presentation of cortical dysplasias. Recent developments in the presurgical
      diagnostic and outcome after operative treatment as well as prognostic factors
      are summarized. Finally, an outlook is given on the development of future novel
      treatment options that might be minimally invasive and help especially the
      patient group who is inoperable or has failed epilepsy surgery.

PMID- 22592416
TI  - Development of a blended model of teaching and learning for nursing students on
      rostered placement to ensure competence in information and communication
      technology for professional practice in Ireland.
AB  - Experiences gained from delivering a Health Informatics for Nurses course in a
      school of nursing and midwifery in a university teaching hospital in Ireland
      suggest that Web-based courses may facilitate an enhanced understanding of course
      content. Nursing education must recognize the importance of information and
      communication technology in nursing to prepare the nursing and midwifery
      profession to embrace current advances in information and communication
      technology in healthcare in Ireland, and ultimately to benefit patient care.

PMID- 22592417
TI  - Sequential assessment of prey through the use of multiple sensory cues by an
      eavesdropping bat.
AB  - Predators are often confronted with a broad diversity of potential prey. They
      rely on cues associated with prey quality and palatability to optimize their
      hunting success and to avoid consuming toxic prey. Here, we investigate a
      predator's ability to assess prey cues during capture, handling, and consumption
      when confronted with conflicting information about prey quality. We used
      advertisement calls of a preferred prey item (the tungara frog) to attract fringe
      lipped bats, Trachops cirrhosus, then offered palatable, poisonous, and
      chemically manipulated anurans as prey. Advertisement calls elicited an attack
      response, but as bats approached, they used additional sensory cues in a
      sequential manner to update their information about prey size and palatability.
      While both palatable and poisonous small anurans were readily captured, large
      poisonous toads were approached but not contacted suggesting the use of
      echolocation for assessment of prey size at close range. Once prey was captured,
      bats used chemical cues to make final, post-capture decisions about whether to
      consume the prey. Bats dropped small, poisonous toads as well as palatable frogs
      coated in toad toxins either immediately or shortly after capture. Our study
      suggests that echolocation and chemical cues obtained at close range supplement
      information obtained from acoustic cues at long range. Updating information about
      prey quality minimizes the occurrence of costly errors and may be advantageous in
      tracking temporal and spatial fluctuations of prey and exploiting novel food
      sources. These findings emphasize the sequential, complex nature of prey
      assessment that may allow exploratory and flexible hunting behaviors.

PMID- 22592418
TI  - FGF23 and mineral metabolism, implications in CKD-MBD.

PMID- 22592419
TI  - C4d as a diagnostic tool in membranous nephropathy.
AB  - INTRODUCTION: membranous nephropathy (MN) is the most common cause of nephrotic
      syndrome in adults. The diagnosis is based on typical findings observed using
      electron microscope (EM) and immunofluorescence (IF) studies. On some occasions,
      tissues are only available for analysis using an optical microscope (OM); in
      these cases, it can be difficult to differentiate between MN and minimal change
      disease (MCD). Recently, the use of C4d immunohistochemical staining has spread.
      Very little information is available regarding C4d deposits in MN. Our study
      consisted of analysing whether C4d staining of samples embedded in paraffin could
      be useful for diagnosing MN. MATERIAL AND METHOD: Ours was a retrospective study
      including all patients diagnosed with MN by renal biopsy in our unit between
      January 2001 and October 2008. We only included adult patients with a definitive
      diagnosis of MN or idiopathic MCD by OM, IF, and ME studies. In October 2008, 3um
      sections of renal tissue fixed in formaldehyde were removed from paraffin and
      rehydrated. The samples were then stained for C4d immunohistochemical analysis
      using anti-human polyclonal antibodies obtained from rabbits. RESULTS: Our study
      included a final sample of 19 patients with MCD and 21 with MN. No C4d deposits
      were observed in any of the glomeruli in patients with MCD, and 100% of these
      patients were classified as negative. However, C4d deposits were detected in 100%
      of patients with MN, and were observable in all glomeruli with a uniform granular
      distribution, demarcating all capillary loops. CONCLUSIONS: C4d
      immunohistochemical staining is a very useful tool for diagnosing MN.

PMID- 22592421
TI  - Factors associated with early peritoneal dialysis catheter replacement in
      Veracruz, Mexico.
AB  - INTRODUCTION: Catheter-related complications in patients on peritoneal dialysis
      lead to decreased effectiveness and discontinuation of the technique, conversion
      to haemodialysis, hospitalisation, and surgical interventions to replace the
      catheter. OBJECTIVES: Determine risk factors for early catheter dysfunction that
      result in the need for replacement. METHODS: We analysed 235 catheters placed by
      open surgery using an infra-umbilical midline incision. Possible risk factors
      included the following: age, sex, body mass index, body surface area, diabetes,
      polycystic kidney disease, previous surgery, time of surgical procedure,
      omentectomy, omentopexy, wound infection and postoperative incisional hernia.
      RESULTS: During the first year, 47 patients (20%) required a catheter replacement
      due to poor function. The most common complications were catheter migration and
      peritonitis (4.3% in both cases), followed by obstruction from omental wrapping
      (3.7%). Univariate analysis showed that patients with catheter dysfunction or
      requiring catheter replacement were younger, with a lower body mass index and
      body surface area (P<.05). There was a significant association of wound infection
      and post-operative incisional hernia with catheter replacement. Omentectomy was
      associated with a low incidence rate of catheter dysfunction/replacement in the
      univariate and logistical regression analyses (odds ratio: 0.275; 95% confidence
      interval: 0.101-0.751; P<.012). CONCLUSIONS: Our catheter placement technique
      offers a low complication rate and good results in the first year after surgery.
      Except for omentectomy, we did not discover any risk factors for catheter
      replacement in our study population. Omentectomy had a protective effect in terms
      of catheter replacement.

PMID- 22592420
TI  - Successful treatment of calcific uraemic arteriolopathy with bisphosphonates.
AB  - BACKGROUND AND OBJECTIVES: Calcific uraemic arteriolopathy (CUA), also known as
      calciphylaxis, is a rare but life-threatening condition that almost exclusively
      affects patients with chronic kidney disease. Several therapies have been
      employed to treat this disease but with irregular results. We report a
      prospective case series of eight patients diagnosed with CUA in our unit between
      2002 and 2010. MATERIAL AND METHOD: The series consisted of eight patients with
      CUA (including 4 men, 5 dialysis patients and 3 with functioning allografts) who
      were treated with bisphosphonates. The diagnosis was by clinical suspicion and a
      confirmatory biopsy. Five patients had a previous history of high calcium
      phosphorus product, 6 had a history of high parathyroid hormone levels
      (>800pg/ml), 4 had undergone parathyroidectomy, 5 had a history of high
      cumulative doses of steroids, and 6 patients were under dicoumarin treatment.
      None of the patients were obese or had diabetes mellitus. RESULTS: In all
      patients, progression of skin lesions stopped between 2 to 4 weeks after starting
      bisphosphonate therapy, with no changes in blood levels of calcium and phosphate.
      Improvement in pain and lesions was faster in patients receiving intravenous
      ibandronate. All of these patients remained on bisphosphonate treatment for at
      least 6 months until the wounds healed completely. No recurrences have been
      observed after follow-up periods between 1 and 9 years. Renal function remained
      stable in transplant recipients. The treatment was well tolerated and no adverse
      effects were observed. CONCLUSIONS: Bisphosphonates could be a new and attractive
      alternative to treat CUA.

PMID- 22592422
TI  - Discrepancies among consensus documents, guidelines, clinical practice and the
      legal framework for the treatment of type 2 diabetes mellitus patients.
AB  - In this paper we analyse the discrepancies that exist in the widespread
      prescription of metformin in patients with type 2 diabetes and the lack of
      guidelines concerning its prescription in the different stages of renal failure.
      This cross-sectional study includes 304 patients with type 2 diabetes treated
      with oral antidiabetic drugs (ADOs) and a glomerular filtration rate (estimated
      GFR) <60ml/min/1.73m2. Patients were attended in consecutive visits to primary
      health centres or in hospital departments of endocrinology or nephrology during
      2010. We studied the frequency of metformin and other ADO prescriptions according
      to renal function and the department in which the patient was treated. The ADO
      most frequently prescribed was metformin (54.9%), followed by repaglinide
      (47.7%), DPP4 inhibitors (28.6%), and sulfonylureas (18.4%). However, in
      nephrology departments, repaglinide was more frequently prescribed than metformin
      (P<.001), whereas in primary health centres, the prescription of DPP4 inhibitors
      increased. In patients with an estimated GFR of 15-29ml/min/1.73m2, metformin
      (13.3%) and sulfonylureas were the least prescribed, whereas metformin was much
      more frequently prescribed (70.0%) when estimated GFR was 45-59ml/min/1.73m2
      (P<.001). In contrast, patients with an estimated GFR of 15-29ml/min/1.73m2 were
      mainly prescribed repaglinide (76.7%), as opposed to patients with an estimated
      GFR of 45-59ml/min/1.73m2 (38.9%) (P<.001). Substantial evidence suggests that
      the recommendations for the use of ADO should be modified. This would lead to
      safely prescribing ADO in patients with an estimated GFR<60ml/min/1.73m2, and
      more importantly in medical practice, according to the law.

PMID- 22592423
TI  - Infliximab in the treatment of amyloidosis secondary to Crohn's disease.
AB  - Secondary amyloidosis (AA) is a severe complication of progressed Crohn&rsquo;s
      disease (CD) for which no effective treatment exists. We present the exceptional
      case of a 33 year-old male with moderate renal failure and proteinuria, who was
      simultaneously diagnosed with AA amyloid nephropathy and oligosymptomatic CD. He
      was treated with infliximab at 5mg/kg/8 weeks for 4 years, azathioprine at 1
      1.5mg/kg/day (first year) and renin-angiotensin-aldosterone system blockers, with
      no complications. Treatment caused a decrease in proteinuria, improved renal
      function, and improved inflammatory parameters over time. Inspired by this case,
      we performed a review of the medical literature and found that infliximab could
      be a useful tool in the early treatment of amyloidosis secondary to CD.

PMID- 22592424
TI  - Analysis of concordance between the bioelectrical impedance vector analysis and
      the bioelectrical impedance spectroscopy in haemodialysis patients.
AB  - INTRODUCTION: The values of body composition provided by the two most commonly
      used bioelectrical impedance systems in Spain, single-frequency bioelectrical
      impedance vector analysis (SF-BIVA) and multi-frequency bioelectrical impedance
      spectroscopy (MF-BIS) are different and not comparable. OBJECTIVE: Analyse
      whether the inter-method variability is due to bioelectrical variables measured
      by the different monitors, or rather due to the equations used to calculate body
      volume and mass. Another objective was to determine whether, despite the inter
      method variability, the classification of hydration status by the two methods is
      consistent. MATERIAL AND METHODS: Bioelectrical impedance was measured by SF-BIVA
      and MF-BIS immediately before a dialysis session in 54 patients on haemodialysis.
      In 38 patients, the study was repeated by SF-BIVA at the end of the same dialysis
      session. RESULTS: Resistance and phase angle values provided by the two monitors
      at a frequency of 50kHz were consistent. For resistance, variability was 1.3% and
      the intra-class correlation coefficient was 0.99. For phase angle, variability
      and the intra-class correlation coefficient were 11.5% and 0.92, respectively.
      The volume values for total body water, extracellular water, fat mass and body
      cell mass were biased, with a level of variability that would not be acceptable
      in clinical practice. The intra-class correlation coefficient also suggested a
      poor level of agreement. SF-BIVA systems define overhydration or dehydration as a
      vector below or above the tolerance ellipse of 75% on the longitudinal axis. MF
      BIS uses two criteria for pre-dialysis hyper-hydration: overhydration (OH)
      greater than 2.5 litres, or greater than 15% of extracellular water. The degree
      of equivalence with the results of the SF-BIVA monitor was better with the second
      criterion (kappa: 0.81, excellent agreement) than with the first one (kappa:
      0.71, acceptable agreement). The MF-BIS system defines post-dialysis normal
      hydration as a difference between OH and ultrafiltratation volume between -1.1
      and 1.1 litres and agreement with the SF-BIVA system for this parameter was
      acceptable (weighted kappa index: 0.64). CONCLUSIONS: The MF-BIS and SF-BIVA
      systems provide similar readings for bioelectrical parameters, and the wide
      variation in the quantification of volume and body mass must be attributed to the
      different equations used for calculation. Furthermore, the criteria used by both
      systems to define both pre- and post-dialysis hydration have an acceptable level
      of equivalence.

PMID- 22592425
TI  - Comment on "Haemodialysis using high cut-off dialysers for treating acute renal
      failure in multiple myeloma".

PMID- 22592426
TI  - Progression of chronic kidney disease. Prevalence of anxiety and depression in
      autosomal dominant polycystic kidney disease.

PMID- 22592427
TI  - Diabetic foot and renal failure. Theoretical and practical considerations.

PMID- 22592428
TI  - Effects of suspending ACE inhibitors and ARBs in advanced chronic kidney disease.

PMID- 22592429
TI  - Microalbuminuria, another use for paricalcitol? Our experience in advanced
      chronic kidney disease.

PMID- 22592430
TI  - Monitoring haemodialysis in the Cabuenes Hospital.

PMID- 22592431
TI  - Topiramate-induced metabolic acidosis: a case study.

PMID- 22592432
TI  - Giant true aneurysm of the radial artery following ligation of an arteriovenous
      fistula for haemodialysis.

PMID- 22592433
TI  - Nephrogenic ascites: a thing of the past?

PMID- 22592434
TI  - Postpartum hemolytic uremic syndrome with multiple organ involvement in a severe
      case.

PMID- 22592435
TI  - Primary sclerosing cholangitis and interstitial nephropathy: an emerging
      association?

PMID- 22592436
TI  - Minimal-change nephropathy in systemic lupus erythematosus.

PMID- 22592437
TI  - Minimal change disease following influenza vaccination and acute renal failure:
      just a coincidence?

PMID- 22592438
TI  - Lanthanum carbonate and peritoneal catheter dysfunction.

PMID- 22592439
TI  - Bilateral renal infarctions.

PMID- 22592440
TI  - Severe hypertriglyceridaemia. Treatment with plasmapheresis.

PMID- 22592442
TI  - Physiological metal uptake by Nostoc punctiforme.
AB  - Trace metals are required for many cellular processes. The acquisition of trace
      elements from the environment includes a rapid adsorption of metals to the cell
      surface, followed by a slower internalization. We investigated the uptake of the
      trace elements Co(2+), Cu(2+), Mn(2+), Ni(2+), and Zn(2+) and the non-essential
      divalent cation Cd(2+) in the cyanobacterium Nostoc punctiforme. For each metal,
      a dose response study based on cell viability showed that the highest non-toxic
      concentrations were: 0.5 MUM Cd(2+), 2 MUM Co(2+), 0.5 MUM Cu(2+), 500 MUM
      Mn(2+), 1 MUM Ni(2+), and 18 MUM Zn(2+). Cells exposed to these non-toxic
      concentrations with combinations of Zn(2+) and Cd(2+), Zn(2+) and Co(2+), Zn(2+)
      and Cu(2+) or Zn(2+) and Ni(2+), had reduced growth in comparison to controls.
      Cells exposed to metal combinations with the addition of 500 MUM Mn(2+) showed
      similar growth compared to the untreated controls. Metal levels were measured
      after one and 72 h for whole cells and absorbed (EDTA-resistant) fractions and
      used to calculate differential uptake rates for each metal. The differences in
      binding and internalisation between different metals indicate different uptake
      processes exist for each metal. For each metal, competitive uptake experiments
      using (65)Zn showed that after 72 h of exposure Zn(2+) uptake was reduced by most
      metals particularly 0.5 MUM Cd(2+), while 2 MUM Co(2+) increased Zn(2+) uptake.
      This study demonstrates that N. punctiforme discriminates between different
      metals and favourably substitutes their uptake to avoid the toxic effects of
      particular metals.

PMID- 22592444
TI  - Coronary sinus ostial atresia associated with functionally single ventricle:
      persistent left superior vena cava should be ligated upon coronary sinus
      unroofing and bidirectional Glenn shunt.
AB  - An 11-month-old boy with a functionally single ventricle, coronary sinus ostial
      atresia, and bilateral superior vena cava (SVC) underwent coronary sinus
      unroofing upon a right bidirectional cavopulmonary shunt. A persistent left SVC
      left open to guarantee dual coronary venous drainage became dilated with
      cephalocaudal blood flow reversal and desaturation. The left SVC was surgically
      ligated on postoperative day 35.

PMID- 22592443
TI  - Nonsymptomatic myocardial injury after radiofrequency and cryoablation: a study
      of children and patients with congenital heart disease.
AB  - The aim of this study was to investigate the degree of myocardial injury
      following catheter radiofrequency (RF) ablation (RFA) or cryoablation and its
      clinical significance in children and patients with congenital heart disease.
      Cardiac troponin T (cTnT) or cardiac troponin I (cTnI), creatine kinase (CK), and
      its cardiac isoenzyme MB (CK-MB) were measured in 269 patients who underwent
      catheter ablation (216 RFA, 53 cryoablation) just before the procedure and again
      6 hours after the end of the procedure. Follow-up studies included
      echocardiography and 12 lead electrocardiographics (ECGs). No clinical, ECG, nor
      ECG signs of ischemia were detected. Biomarkers were increased in 57.7-75.5 %. A
      linear regression analysis illustrated the ablation target site and the number of
      RF applications as a function of higher cTnI and cTnT levels, with the maximum
      increase due to ventricular ablation and higher numbers of RF applications. No
      significant difference in cTnT levels after RFA or cryoablation were observed for
      AV nodal reentrant tachycardia procedures and no significant differences were
      observed after nonirrigated tip or irrigated tip RFA in atrial wall or
      ventricular wall ablation. Elevations in both troponin T and troponin I levels
      were commonly observed after ablation, especially in ventricular wall ablation as
      well as with increasing numbers of radiofrequency applications. However, unlike
      in patients with acute coronary syndrome, these elevated levels had no specific
      significance. Reference values for each ablation target site were proposed in
      order to potentially detect additional subclinical injuries to the coronary
      arteries.

PMID- 22592445
TI  - Factors associated with prolonged recovery after the arterial switch operation
      for transposition of the great arteries in infants.
AB  - This study aimed specifically to identify the predictors of prolonged recovery
      after the arterial switch operation for transposition of the great arteries in
      infants. The clinical records of all infants admitted to the surgical intensive
      care unit (SICU) between January 2000 and March 2011 after an arterial switch
      operation were retrospectively reviewed. The cohort was divided into a prolonged
      recovery group that included all patients who exceeded the 75th percentile for
      duration of SICU stay and a standard recovery group that included all the
      remaining patients. Of the 102 patients in the final analysis, 31 experienced
      prolonged recovery. The median SICU stay was 18 days (range, 14-58 days) for the
      patients in the prolonged recovery group and only 8 days (range, 5-13 days) for
      the patients in the standard recovery group. After univariate analysis, a
      stepwise logistic regression model analysis was used to compare the demographic
      data as well as the pre-, intra-, and postoperative variables between the two
      groups. Of all the variables analyzed, high postbypass serum lactate level [odds
      ratio (OR), 2.610; 95 % confidence interval (CI), 1.464-4.653; p = 0.039], need
      for larger volume of resuscitation fluid (OR, 3.154; 95 % CI, 1.751-5.682; p =
      0.018), and noninfectious pulmonary complication (OR, 2.844; 95 % CI, 1.508
      5.363; p = 0.025) were identified as independent risk factors for prolonged
      recovery among infants undergoing an arterial switch operation for transposition
      of the great arteries.

PMID- 22592446
TI  - Smoking-attributable mortality by cause in the United States: revising the CDC's
      data and estimates.
AB  - INTRODUCTION: Smoking is the leading cause of preventable mortality in the United
      States, but the methods and data used in the Centers for Disease Control and
      Prevention's (CDC) published estimates of adult smoking-attributable mortality
      have not been substantially revised since their introduction in the 1980s.
      METHODS: We employed the CDC's general methodology for estimating smoking
      attributable mortality but produced improved estimates by using recent,
      nationally representative relative risk data from the National Health Interview
      Survey-Linked Mortality Files and adjusting for confounding risk factors. We also
      produced estimates by smoking status and over time. RESULTS: Our use of more
      recent and nationally representative relative risks tended to decrease estimates
      of smoking deaths for men and increased estimates for women compared with the
      CDC's estimates. Adjustment for confounding factors further refined the
      estimates, particularly by smoking status. We estimated 200,000 smoking
      attributable deaths for men and 180,000 smoking-attributable deaths for women in
      the United States in 2004. Estimated smoking-attributable mortality has finally
      begun to decline for both U.S. men and women. CONCLUSIONS: Our approach offers
      several substantive improvements in the estimation of smoking-attributable
      mortality by cause for the United States. Cigarette smoking remains a leading
      cause of preventable mortality in the United States, but we estimate that the
      number of smoking-attributable deaths has begun to decline.

PMID- 22592447
TI  - Counseling nondaily smokers about secondhand smoke as a cessation message: a
      pilot randomized trial.
AB  - INTRODUCTION: Nondaily smoking represents a substantial and growing fraction of
      smokers, many of whom do not consider themselves smokers or at risk of tobacco
      related diseases and, so, may be less responsive to counseling content contained
      in traditional cessation interventions. This study compares the effects brief
      counseling interventions (<20 min) focused on the harm smoking does to themselves
      (harm to self, HTS) versus the harm their secondhand smoke (SHS) does to others
      (harm to others, HTO) among nondaily smokers. METHODS: Randomized trial of 52
      nondaily smokers (smoked in the past week, but not daily) recruited between
      September 2009 and June 2010; 40 completed the study. We measured changes in
      motivation and smoking status at 3 months postintervention. RESULTS: There was a
      difference in quitting between the two groups, with 9.5% (2 out of 21) for HTS
      and 36.8% (7 out of 19) for HTO subjects reporting not smoking any cigarettes in
      the prior week (p = .06 by Fisher exact test and .035 by likelihood-ratio chi
      square). Motivation and self-efficacy increased from baseline to 3-month follow
      up, but not differentially by intervention group. CONCLUSIONS: Consistent with
      findings from research conducted by the tobacco industry as early as the 1970s
      that concluded that social smokers feel immune from the personal health effects
      of tobacco but are concerned about the consequences of their SHS on others,
      educating nondaily smokers about the dangers of SHS to others appears to be a
      more powerful cessation message than traditional smoking cessation counseling
      that emphasizes the harmful consequences to the smoker.

PMID- 22592448
TI  - High yield recombinant expression, characterization and homology modeling of two
      types of cis-epoxysuccinic acid hydrolases.
AB  - The cis-epoxysuccinate hydrolases (CESHs), members of epoxide hydrolase, catalyze
      cis-epoxysuccinic acid hydrolysis to form D: (-)-tartaric acid or L: (+)-tartaric
      acid which are important chemicals with broad scientific and industrial
      applications. Two types of CESHs (CESH[D: ] and CESH[L: ], producing D: (-)- and
      L: (+)-tartaric acids, respectively) have been reported with low yield and
      complicated purification procedure in previous studies. In this paper, the two
      CESHs were overexpressed in Escherichia coli using codon-optimized genes. High
      protein yields by one-step purifications were obtained for both recombinant
      enzymes. The optimal pH and temperature were measured for both recombinant CESHs,
      and the properties of recombinant enzymes were similar to native enzymes.
      Kinetics parameters measured by Lineweaver-Burk plot indicates both enzymes
      exhibited similar affinity to cis-epoxysuccinic acid, but CESH[L: ] showed much
      higher catalytic efficiency than CESH[D: ], suggesting that the two CESHs have
      different catalytic mechanisms. The structures of both CESHs constructed by
      homology modeling indicated that CESH[L: ] and CESH[D: ] have different
      structural folds and potential active site residues. CESH[L: ] adopted a typical
      alpha/beta-hydrolase fold with a cap domain and a core domain, whereas CESH[D: ]
      possessed a unique TIM barrel fold composed of 8 alpha-helices and 8 beta
      strands, and 2 extra short alpha-helices exist on the top and bottom of the
      barrel, respectively. A divalent metal ion, preferred to be zinc, was found in
      CESH[D: ], and the ion was proved to be crucial to the enzymatic activity. These
      results provide structural insight into the different catalytic mechanisms of the
      two CESHs.

PMID- 22592449
TI  - Localization of rabies virus glycoprotein into the endoplasmic reticulum produces
      immunoprotective antigen.
AB  - Rabies virus surface glycoprotein (rabies G-protein) with (G+RS) and without (G
      RS) endoplasmic reticulum retrieval signal was expressed and characterized in
      tobacco plants. Transgenically expressed rabies G-protein was estimated at 0.015
      0.38 % of total leaf protein. The relative migration of the rabies G-protein on
      SDS-PAGE was at the position, as anticipated for the viral coat protein (~66
      kDa). Immunolocalization by confocal microscopy established that immunoprotective
      G+RS expressed in tobacco was primarily confined to ER. G+RS showed binding to
      Con A lectin and was susceptible to N-glycosidase F activity similar to native
      rabies G-protein. However, the G-RS transgenically expressed in tobacco leaves
      was glycosylated differently and was resitant to N-glycosidase F. Immunological
      studies and Rapid Fluorescent Foci Inhibition Test (RFFIT) showed that G+RS was
      immunogenic and immunoprotective, whereas G-RS was moderately immunogenic but non
      protective against live virus challenge. Hence, plants can express the antigenic
      component of rabies virus with suitable glycosylation, which is important to give
      protection against rabies virus infection.

PMID- 22592451
TI  - Radiofrequency identification: exploiting an old technology for measuring nurse
      time and motion.
AB  - A national campaign is underway to increase the amount of time staff nurses spend
      at the bedside of hospitalized patients through redesign of the work environment.
      This kind of work redesign requires robust data depicting what nurses do and how
      they spend their time. Historically, these kinds of data have been difficult,
      costly, and time consuming to collect. Wireless capture of data on the movement
      of humans within the work environment (ie, time and motion) is now possible
      through radiofrequency identification technology. When small tracking devices the
      size of a quarter are affixed to their clothing, the movement of nurses
      throughout a patient care unit can be monitored. The duration and frequency of
      patient interaction are captured along with the duration of time spent in other
      locations of interest to include nurses' station, supply room, medication room,
      doctors' station, electronic documentation stations, family waiting rooms, and
      the hallway. Patterns of nurse movement and time allocation can be efficiently
      identified, and the effects of staffing practices, workflows, and unit layout
      evaluated. Integration of radiofrequency identification time and motion data with
      other databases enables nurse leaders to link nursing time to important cost and
      quality outcomes. Nurse leaders should explore the usefulness of radiofrequency
      identification technology in addressing data needs for nurse time and motion.

PMID- 22592452
TI  - Student outcomes of distance learning in nursing education: an integrative
      review.
AB  - Distance learning offers a distinctive environment to educate nursing students.
      While there is a significant body of evidence in the literature related to
      course, program, and faculty outcomes of distance education, little attention has
      been given by researchers to evaluate student outcomes, with the exception of
      student satisfaction. There is a need to evaluate and translate findings related
      to student outcomes in distance learning into educational practice. Integrative
      reviews offer one strategy to contribute to evidence-based teaching practice
      initiatives. A search of available published qualitative and quantitative
      research on student outcomes of distance learning from 1999 to 2009 was conducted
      using a number of databases. Astin's Input-Environment-Output conceptual model
      provided a framework for this review. Thirty-three studies met the inclusion
      criteria. Bothcognitive and affective student outcomes emerged. The cognitive
      outcomes were student learning, learning process, and technology proficiency.
      Affective outcomes included personal and professional growth, satisfaction, and
      connectedness. Implications, recommendations, and future research are discussed.

PMID- 22592453
TI  - Determinants of primary care nurses' intention to adopt an electronic health
      record in their clinical practice.
AB  - A provincial electronic health record is being developed in the Province of
      Quebec (and in all other provinces in Canada), and authorities hope that it will
      enable a safer and more efficient healthcare system for citizens. However, the
      expected benefits can occur only if healthcare professionals, including nurses,
      adopt this technology. Although attention to the use of the electronic health
      record by nurses is growing, better understanding of nurses' intention to use an
      electronic health record is needed and could help managers to better plan its
      implementation. This study examined the factors that influence primary care
      nurses' intention to adopt the provincial electronic health record, since
      intention influences electronic health record use and implementation success.
      Using a modified version of Ajzen's Theory of Planned Theory of Planned Behavior,
      a questionnaire was developed and pretested. Questionnaires were distributed to
      199 primary care nurses. Multiple hierarchical regression indicated that the
      Theory of Planned Behavior variables explained 58% of the variance in nurses'
      intention to adopt an electronic health record. The strong intention to adopt the
      electronic health record is mainly determined by perceived behavioral control,
      normative beliefs, and attitudes. The implications of the study are that
      healthcare managers could facilitate adoption of an electronic health record by
      strengthening nurses' intention to adopt the electronic health record, which in
      turn can be influenced through interventions oriented toward the belief that
      using an electronic health record will improve the quality of patient care.

PMID- 22592454
TI  - Statement of the AGNP-Work Group "Child and Adolescent Pharmacology" on the
      decision of the Joint Federal Committee (GBA) of the 17/02/2011 to combine
      escitalopram with citalopram into a fixed amount group.

PMID- 22592455
TI  - Partial heat acclimation of athletes with spinal cord lesion.
AB  - Heat acclimation (HA) can improve thermoregulatory stability in able-bodied
      athletes in part by an enhanced sweat response. Athletes with spinal cord lesion
      are unable to sweat below the lesion and it is unknown if they can HA. Five
      paralympic shooting athletes with spinal cord lesion completed seven consecutive
      days HA in hot conditions (33.4 +/- 0.6  degrees C, 64.8 +/- 3.7 %rh). Each HA
      session consisted of 20 min arm crank exercise at 50 % [Formula: see text]
      followed by 40 min rest, or simulated shooting. Aural temperature (T (aur)) was
      recorded throughout. Body mass was assessed before and after each session and a
      sweat collection swab was fixed to T12 of the spine. Fingertip whole blood was
      sampled at rest on days 1 and 7 for estimation of the change in plasma volume.
      Resting T (aur) declined from 36.3 +/- 0.2  degrees C on day 1 to 36.0 +/- 0.2 
      degrees C by day 6 (P < 0.05). During the HA sessions mean, T (aur) declined from
      37.2 +/- 0.2  degrees C on day 1, to 36.7 +/- 0.3  degrees C on day 7 (P < 0.05).
      Plasma volume increased from day 1 by 1.5 +/- 0.6 % on day 7 (P < 0.05). No sweat
      secretion was detected or changes in body mass observed from any participant.
      Repeated hyperthermia combined with limited evaporative heat loss was sufficient
      to increase plasma volume, probably by alterations in fluid regulatory hormones.
      In conclusion, we found that although no sweat response was observed, athletes
      with spinal cord lesion could partially HA.

PMID- 22592456
TI  - Overload training inhibits phagocytosis and ROS generation of peritoneal
      macrophages: role of IGF-1 and MGF.
AB  - We tested the hypothesis that overload training inhibits the phagocytosis and the
      reactive oxygen species (ROS) generation of peritoneal macrophages (Mphis), and
      that insulin-like growth factor-1(IGF-1) and mechano-growth factor (MGF) produced
      by macrophages may contribute to this process. Rats were randomized to two
      groups, sedentary control group (n = 10) and overload training group (n = 10).
      The rats of overload training group were subjected to 11 weeks of experimental
      training protocol. Blood sample was used to determine the content of hemoglobin,
      testosterone, and corticosterone. The phagocytosis and the ROS generation of
      Mphis were measured by the uptake of neutral red and the flow cytometry,
      respectively. IGF-1 and MGF mRNA levels in Mphis were determined by real-time
      PCR. In addition, we evaluated the effects of IGF-1 and MGF peptide on
      phagocytosis and ROS generation of Mphis in vitro. The data showed that overload
      training significantly decreased the body weight (19.3 %, P < 0.01), the
      hemoglobin (13.5 %, P < 0.01), the testosterone (55.3 %, P < 0.01) and the
      corticosterone (40.6 %, P < 0.01) in blood. Moreover, overload training
      significantly decreased the phagocytosis (27 %, P < 0.05) and the ROS generation
      (35 %, P < 0.01) of Mphis. IGF-1 and MGF mRNA levels in Mphis from overload
      training group increased significantly compared with the control group (21-fold
      and 92-fold, respectively; P < 0.01). In vitro experiments showed that IGF-1 had
      no significant effect on the phagocytosis and the ROS generation of Mphis. Unlike
      IGF-1, MGF peptide impaired the phagocytosis of Mphis in dose-independent manner.
      In addition, MGF peptide of some concentrations (i.e., 1, 10, 50, 100 ng/ml)
      significantly inhibited the ROS generation of Mphis. These results suggest that
      overload training inhibits the phagocytosis and the ROS generation of peritoneal
      macrophages, and that MGF produced by macrophages may play a key role in this
      process. This may represent a novel mechanism of immune suppression induced by
      overload training.

PMID- 22592458
TI  - Effects of aluminium water treatment residuals, used as a soil amendment to
      control phosphorus mobility in agricultural soils.
AB  - Phosphorus (P) leaching from agricultural soils is a serious environmental
      concern. Application of aluminium water treatment residuals (Al-WTRs) at a rate
      of 20 Mg ha(-1) to clay soils from central Sweden significantly increased mean
      topsoil P sorption index (PSI) from 4.6 to 5.5 MUmol kg(-1) soil. Mean degree of
      P saturation in ammonium lactate extract (DPS-AL) significantly decreased from 17
      to 13%, as did plant-available P (P-AL). Concentrations of dissolved reactive P
      (DRP) decreased by 10-85% in leaching water with Al-WTR treatments after exposure
      of topsoil lysimeters to simulated rain. Soil aggregate stability (AgS) for 15
      test soils rarely improved. Three soils (clay loam, silty loam and loam sand)
      were tested in greenhouse pot experiments. Aluminium-WTR application of 15 or 30
      ton ha(-1) to loam sand and a clay loam with P-AL values of 80-100 mg kg(-1) soil
      significantly increased growth of Italian ryegrass when fertilised with P but did
      not significantly affect growth of spring barley on any soil. Al-WTR should only
      be applied to soils with high P fertility where improved crop production is not
      required.

PMID- 22592457
TI  - Correlation of expression of hypoxia-related proteins with prognosis in oral
      squamous cell carcinoma patients.
AB  - INTRODUCTION: Hypoxia plays a major role in tumor progression, therapy resistance
      and for prognosis of oral squamous cell carcinoma (OSCC). The crucial step as a
      response to hypoxia is the activation and stabilization of the alpha subunit of
      hypoxia inducible factor 1 (HIF-1alpha). HIF-1: HIF-1 regulates the expression of
      different genes to adapt the tumor cells to reduced oxygenation. The HIF-1 system
      is intrinsic regulated by von Hippel-Lindau protein (pVHL). Main downstream
      proteins are the glucose transporter 1 (GLUT-1), carbonic anhydrase IX (CAIX),
      and vascular endothelial growth factor (VEGF). For therapeutical stratification
      in OSCC, it is important to understand the mechanism caused by hypoxic stress and
      to comprehend the resulting adaptive process in cancer cells. Therefore, an
      overview of HIF-1alpha-depending protein expression, focussed on the expression
      of GLUT-1, CAIX, and VEGF and their prognostic significance in OSCC is given.
      CONCLUSION: Several unique roles of hypoxic pathway in the context of tumor
      progression are described in this review. As a consequence, a marker panel is
      proposed to allow a more individualized prognosis in OSCC patients. This marker
      panel should include beside HIF-1alpha, pVHL, and GLUT-1.

PMID- 22592459
TI  - Global sensitivity analysis of the BSM2 dynamic influent disturbance scenario
      generator.
AB  - This paper presents the results of a global sensitivity analysis (GSA) of a
      phenomenological model that generates dynamic wastewater treatment plant (WWTP)
      influent disturbance scenarios. This influent model is part of the Benchmark
      Simulation Model (BSM) family and creates realistic dry/wet weather files
      describing diurnal, weekend and seasonal variations through the combination of
      different generic model blocks, i.e. households, industry, rainfall and
      infiltration. The GSA is carried out by combining Monte Carlo simulations and
      standardized regression coefficients (SRC). Cluster analysis is then applied,
      classifying the influence of the model parameters into strong, medium and weak.
      The results show that the method is able to decompose the variance of the model
      predictions (R(2)> 0.9) satisfactorily, thus identifying the model parameters
      with strongest impact on several flow rate descriptors calculated at different
      time resolutions. Catchment size (PE) and the production of wastewater per person
      equivalent (QperPE) are two parameters that strongly influence the yearly average
      dry weather flow rate and its variability. Wet weather conditions are mainly
      affected by three parameters: (1) the probability of occurrence of a rain event
      (Llrain); (2) the catchment size, incorporated in the model as a parameter
      representing the conversion from mm rain . day(-1) to m(3) . day(-1) (Qpermm);
      and, (3) the quantity of rain falling on permeable areas (aH). The case study
      also shows that in both dry and wet weather conditions the SRC ranking changes
      when the time scale of the analysis is modified, thus demonstrating the potential
      to identify the effect of the model parameters on the fast/medium/slow dynamics
      of the flow rate. The paper ends with a discussion on the interpretation of GSA
      results and of the advantages of using synthetic dynamic flow rate data for WWTP
      influent scenario generation. This section also includes general suggestions on
      how to use the proposed methodology to any influent generator to adapt the
      created time series to a modeller's demands.

PMID- 22592460
TI  - Solar degradation of Direct Blue 71 using surface modified iron doped ZnO hybrid
      nanomaterials.
AB  - This paper reports photodegradation of Direct Blue 71 under irradiation by
      sunlight. We synthesized Fe:ZnO nanomaterials under mild hydrothermal conditions
      (P = autogenous, T = 100  degrees C, t = 18 h). The precursors were Fe(2)O(3) as
      dopant, n-butylamine as surface modifier, NaOH as mineralizer and reagent grade
      ZnO. The systematic experiments on the photodegradation of Direct Blue 71 were
      carried out by changing different effective parameters. The variables in this
      study were type of nanomaterials synthesized (4 types), nanomaterial dosage (0.4
      1.0 g/L), contact time (30-120 min), pH (3-11), and dye concentration (20-100
      ppm). The photodegradation efficiency was determined using a UV-Vis
      spectrophotometer. Determination of total organic carbon (TOC) amount was used to
      find out mineralization efficiency. Our experimental results revealed that the
      nanomaterials synthesized had higher efficiency compared with the reagent grade
      ZnO. The best efficiency was achieved at the following conditions: 1.0 g/L
      nanomaterials loading, 120 min contact time, pH 5, and photodegradation
      efficiency from more than 75 up to 99% depending upon the dye concentration.

PMID- 22592461
TI  - Water network cost optimization in a paper mill based on a new library of
      mathematical models.
AB  - The increasing costs associated with water supply and the disposal of wastewater
      has stimulated industries to seek more efficient water management systems.
      Mathematical modelling and simulation can be a very valuable tool for the study
      of the multiple alternatives available whilst assessing optimum solutions for
      water management in industry. This study introduces a new steady state model
      library able to reproduce industrial water circuits. It has been implemented in a
      novel software framework for the representation, simulation and optimization of
      industrial water networks. A water circuit representing a paper mill has been
      modelled and simulated showing the capability to reproduce real case studies.
      Alternative scenarios for the water network have also been tested to assess the
      capability of the models to optimize water circuits minimizing total cost.

PMID- 22592462
TI  - Organic biowastes blend selection for composting industrial eggshell by-product:
      experimental and statistical mixture design.
AB  - Composting is one of the technologies recommended for pre-treating industrial
      eggshells (ES) before its application in soils, for calcium recycling. However,
      due to the high inorganic content of ES, a mixture of biodegradable materials is
      required to assure a successful procedure. In this study, an adequate organic
      blend composition containing potato peel (PP), grass clippings (GC) and wheat
      straw (WS) was determined by applying the simplex-centroid mixture design method
      to achieve a desired moisture content, carbon: nitrogen ratio and free air space
      for effective composting of ES. A blend of 56% PP, 37% GC and 7% WS was selected
      and tested in a self heating reactor, where 10% (w/w) of ES was incorporated.
      After 29 days of reactor operation, a dry matter reduction of 46% was achieved
      and thermophilic temperatures were maintained during 15 days, indicating that the
      blend selected by statistical approach was adequate for composting of ES.

PMID- 22592463
TI  - Towards mechanistic models for activated sludge flocculation under different
      conditions based on inverse problems.
AB  - Experimental data of Ca-induced activated sludge flocculation under different
      conditions of temperature and dissolved oxygen are investigated in order to model
      the influence of changing physical and chemical factors. However, current kernel
      structures for collision frequency and efficiency are unable to describe
      activated sludge flocculation data. Therefore, an earlier developed methodology
      based on an inverse problem is applied, yielding empirical models, to find out
      how flocculation is affected by these different environmental conditions. This
      contribution shows the useful application of inverse problems to improve the
      understanding of complex aggregation mechanisms.

PMID- 22592464
TI  - Evaluation and thermodynamic calculation of ureolytic magnesium ammonium
      phosphate precipitation from UASB effluent at pilot scale.
AB  - The removal of phosphate as magnesium ammonium phosphate (MAP, struvite) has
      gained a lot of attention. A novel approach using ureolytic MAP crystallization
      (pH increase by means of bacterial ureases) has been tested on the anaerobic
      effluent of a potato processing company in a pilot plant and compared with
      NuReSys((r)) technology (pH increase by means of NaOH). The pilot plant showed a
      high phosphate removal efficiency of 83 +/- 7%, resulting in a final effluent
      concentration of 13 +/- 7 mg . L(-1) PO(4)-P. Calculating the evolution of the
      saturation index (SI) as a function of the remaining concentrations of Mg(2+),
      PO(4)-P and NH(4)(+) during precipitation in a batch reactor, resulted in a good
      estimation of the effluent PO(4)-P concentration of the pilot plant, operating
      under continuous mode. X-ray diffraction (XRD) analyses confirmed the presence of
      struvite in the small single crystals observed during experiments. The
      operational cost for the ureolytic MAP crystallization treating high phosphate
      concentrations (e.g. 100 mg . L(-1) PO(4)-P) was calculated as 3.9 ? kg(-1)
      P(removed). This work shows that the ureolytic MAP crystallization, in
      combination with an autotrophic nitrogen removal process, is competitive with the
      NuReSys((r)) technology in terms of operational cost and removal efficiency but
      further research is necessary to obtain larger crystals.

PMID- 22592466
TI  - Effects of oxidant concentration and temperature on decolorization of azo dye:
      comparisons of UV/Fenton and UV/Fenton-like systems.
AB  - This study applies photo-Fenton and photo-Fenton-like systems to decolorize C.I.
      Reactive Red 2 (RR2). The oxidants were H(2)O(2) and Na(2)S(2)O(8); Fe(2+),
      Fe(3+), and Co(2+) were used to activate these two oxidants. The effects of
      oxidant concentration (0.3-2 mmol/L) and temperature (25-55  degrees C) on
      decolorization efficiency of the photo-Fenton and photo-Fenton-like systems were
      determined. The decolorization rate constants (k) of RR2 in the tested systems
      are consistent with pseudo-first-order kinetics. The rate constant increased as
      oxidant concentration and temperature increased. Activation energies of RR2
      decolorization in the UV/H(2)O(2)/Fe(2+), UV/H(2)O(2)/Fe(3+),
      UV/Na(2)S(2)O(8)/Fe(2+) and UV/Na(2)S(2)O(8)/Fe(3+) systems were 32.20, 39.54,
      35.54, and 51.75 kJ/mol, respectively.

PMID- 22592465
TI  - Photodegradation of aqueous reactive dye using TiO(2)/zeolite admixtures in a
      continuous flow reactor.
AB  - The photocatalytic degradation of an organic dye, i.e. reactive blue 19 (RB19),
      was studied by employing different TiO(2)/zeolite (TZ) photocatalysts, which have
      TiO(2)/(TiO(2) + zeolite) weight ratios ranging from 20 to 80%, in a continuous
      flow system. Three light sources including two UV lights (i.e. lambda(max,254 nm)
      and lambda(max,365 nm)) and natural sunlight were used. The results showed that
      the decoloring rate of RB19 increased as the amount of TiO(2) in the TZ catalyst
      increased. The photodegradation of RB19 exhibited pseudo-first-order kinetics
      with respect to the concentration of RB19. Almost 100% of initial RB19 was
      mineralized under the controlled conditions in this study. And the activities of
      the prepared photocatalysts were retained after long-term durability experiments.
      Compared with UV lights (i.e. lambda(max,254 nm) and lambda(max,365 nm)), the
      decoloring efficiency of RB19 was significantly increased under natural sunlight
      illumination, which is likely due to the long-wavelength incident light that
      photoexcited RB19 and accelerated the degradation rate of RB19 radicals by the UV
      fraction of sunlight.

PMID- 22592467
TI  - Treatment of anaerobically digested dairy manure in a two-stage biofiltration
      system.
AB  - High concentrations of ammonium and phosphate present a challenge to cost
      effective treatment of anaerobically digested dairy manure. This study
      investigated the efficacy of a two-stage biofiltration system for passive
      treatment of digested dairy manure. The first stage pebble filters were batch
      loaded. When the slurry-like digested dairy manure was retained on pebble beds,
      soluble contaminants were removed before liquid infiltrated over 8-17 days. The
      pebble filters removed 70% of soluble chemical oxygen demand, 71% of soluble
      biochemical oxygen demand, 75% of ammonium, and 68% of orthophosphate. Nitrogen
      removal was attributed to the conventional nitrification - denitrification
      process and novel nitritation - anammox process. Aerobic ammonium oxidizing and
      anammox bacteria accounted for 25 and 23% of all bacteria, respectively, in the
      filtrate of the pebble filters. The longer it took for filtration, the greater
      the removal efficiency of soluble contaminants. The second stage sand filters had
      removal efficiencies of 17% for soluble chemical oxygen demand, 45% for soluble
      biochemical oxygen demand, 43% for ammonium, and 16% for orthophosphate during
      batch operations at a hydraulic retention time of 7 days. Aerobic ammonium
      oxidation and anammox were primarily responsible for nitrogen removal in the sand
      filters. Vegetation made an insignificant difference in treatment performance of
      the sand filters.

PMID- 22592468
TI  - Gene-expression programming for flip-bucket spillway scour.
AB  - During the last two decades, researchers have noticed that the use of soft
      computing techniques as an alternative to conventional statistical methods based
      on controlled laboratory or field data, gave significantly better results. Gene
      expression programming (GEP), which is an extension to genetic programming (GP),
      has nowadays attracted the attention of researchers in prediction of hydraulic
      data. This study presents GEP as an alternative tool in the prediction of scour
      downstream of a flip-bucket spillway. Actual field measurements were used to
      develop GEP models. The proposed GEP models are compared with the earlier
      conventional GP results of others (Azamathulla et al. 2008b; RMSE = 2.347, delta
      = 0.377, R = 0.842) and those of commonly used regression-based formulae. The
      predictions of GEP models were observed to be in strictly good agreement with
      measured ones, and quite a bit better than conventional GP and the regression
      based formulae. The results are tabulated in terms of statistical error measures
      (GEP1; RMSE = 1.596, delta = 0.109, R = 0.917) and illustrated via scatter plots.

PMID- 22592469
TI  - Anaerobic degradation of purified terephthalic acid wastewater using a novel,
      rapid mass-transfer circulating fluidized bed.
AB  - The anaerobic treatability of purified terephthalic acid (PTA) wastewater in a
      novel, rapid mass-transfer fluidized bed reactor using brick particles as porous
      carrier materials was investigated. The reactor operation was stable after a
      short 34 day start-up period, with chemical oxygen demand (COD) removal
      efficiency between 65 and 75%, terephthalate (TA) removal efficiency between 60%
      and 70%, and system organic loading rate (OLR) increasing from 7.37 to 18.52 kg
      COD/m(3) d. The results demonstrate that the reactor is very efficient, and
      requires a low hydraulic retention time (HRT) of 8 h to remove both TA and COD
      from the high-concentration PTA wastewater. The system also has high resistance
      capacity to varied OLR.

PMID- 22592470
TI  - Impacts of nutrients and related environmental factors on distribution and size
      structure of Noctiluca scintillans populations of the eutrophic Tha Chin estuary,
      Thailand.
AB  - This study aimed to analyze the impacts of nutrients and related aquatic factors
      on changes in the Noctiluca population of the Tha Chin estuary, a nutrient-rich
      estuary located in the inner Gulf of Thailand. Field surveys were carried out at
      30 stations during November 2009 to August 2010. The results indicated high
      levels of dissolved inorganic nitrogen (DIN; 13.89-46.99 MUmol/L) and PO(4)(3-)-P
      (0.20-3.05 MUmol/L) where the Noctiluca red tide occurred, particularly during
      the high-loading period. Dense populations were usually found in the outer part
      of the estuary with comparatively high salinity (25-29 psu). The highest
      Noctiluca density was 72,333 cells L(-1) and the cell diameters ranged between
      360 and 460 MUm. Proportions of small-sized cells (P(s); less than 300 MUm)
      varied over time. In this study, P(s) showed a positive correlation with levels
      of PO(4)(3-)-P, while the total population density was significantly affected by
      levels of NH(4)(+)-N and DIN (p < 0.05). Overall, PO(4)(3-)-P influenced the
      development of the Noctiluca red tide, with the limitation of PO(4)(3-)-P levels
      to below 1 MUmol/L suggested for controlling Noctiluca red tide outbreaks at
      their origin. To support environmental conservation and maintain sustainable
      production in the estuary, the levels of PO(4)(3-)-P should be considered for the
      further effective development of water quality standards in estuarine zones.

PMID- 22592471
TI  - Use of laboratory-grown bacterial alginate in copper removal.
AB  - Industrial production leads to toxic heavy metal pollution in water bodies.
      Copper is one of the examples that requires removal from effluents before being
      discharged. It is difficult and sometimes very expensive to remove toxic heavy
      metals by conventional treatment techniques. This study aims to remove copper by
      the use of bacterial alginate as a non-conventional technique. Bacterial
      alginates (natural polymers composed of mannuronic and guluronic acid monomers)
      were synthesized by Azotobacter vinelandii ATCC((r)) 9046 in a laboratory
      fermentor under controlled environmental conditions. The alginates produced, with
      a range of different characteristics in terms of monomer distribution and
      viscosity, were investigated for maximum copper uptake capacities. The average
      copper uptake capacities of alginates produced were found to be about 1.90 mmol/L
      Cu(2+)/g alginate. Although the GG-block amount of alginates was varied from 12
      to 87% and culture broth viscosities were changed within the range of 1.47 and 14
      cP, neither the block distribution nor viscosities of alginate samples
      considerably affected the copper uptake of alginates.

PMID- 22592472
TI  - Degradation of 4-chlorophenol by the anodic-cathodic cooperative effect with a
      Pd/MWNT gas-diffusion electrode.
AB  - Pd/multi-walled carbon nanotubes (MWNTs) catalyst used for the gas-diffusion
      electrode was prepared by ethylene glycol (EG) reduction and characterized by the
      X-ray diffraction (XRD) and scanning electron microscope (SEM). The results
      indicated that Pd particles with an average size of 8.0 nm were highly dispersed
      in the MWNTs with amorphous structure. In a diaphragm electrolysis system with a
      Ti/RuO(2)/IrO(2) anode and the Pd/MWNT gas diffusion cathode, the degradation of
      4-chlorophenol was performed by a combination of electrochemical reduction and
      oxidation. The combined process was in favor of improving 4-chlorophenol
      degradation efficiency. The optimum reaction conditions were as following:
      initial pH 7, aeration with hydrogen and air. Under the optimized electrolysis
      conditions the removal of 4-chlorophenol in the anodic and cathodic compartments
      were 98.5 and 90.5%, respectively. Additionally, based on the analysis of
      electrolysis intermediates using high performance liquid chromatography (HPLC)
      and ion chromatography (IC), the electrolysis degradation of 4-chlorophenol was
      proposed containing the intermediates, such as phenol, hydroquinone,
      benzoquinone, maleic acid, fumaric acid, succinic acid, malonic acid, oxalic
      acid, acetic acid and formic acid.

PMID- 22592473
TI  - Simultaneous photocatalytic oxidation of pharmaceuticals and inactivation of
      Escherichia coli in wastewater treatment plant effluents with suspended and
      immobilised TiO(2).
AB  - Simultaneous Escherichia coli inactivation and oxidation of pharmaceuticals in
      simulated wastewater treatment plant effluents has been investigated using a
      photocatalytic treatment with TiO(2) in suspension and immobilised onto a fixed
      bed reactor. Non-photocatalytic reference experiments of dark adsorption and
      photolysis showed a higher sensitivity of E. coli towards the chemical
      composition of water in comparison with the concentration of pharmaceuticals that
      remains unaffected. Moreover, it must be underlined that the presence of
      pharmaceuticals (including antibiotics) did not seem to affect the bacterial
      viability at such low concentrations. Concerning photocatalytic experiments, both
      suspended and immobilised TiO(2) were able to simultaneously inactivate and
      oxidise both kinds of pollutants (bacteria and pharmaceuticals). The fixed-bed
      reactor showed similar activity to that of the slurry without deactivation after
      several cycles of reuse. That makes TiO(2) photocatalysis a quite interesting
      technology for the treatment of drinking water supplies or wastewater plant
      effluents, allowing the removal of emerging contaminants such as pharmaceuticals
      during the disinfection treatment.

PMID- 22592474
TI  - Analysis of treated wastewater reuse potential for irrigation in Sicily.
AB  - In Mediterranean countries, water shortage is becoming a problem of high concern
      affecting the local economy, mostly based on agriculture. The problem is not only
      the scarcity of water in terms of average per capita, but the high cost to make
      water available at the right place, at the right time with the required quality.
      In these cases, an integrated approach for water resources management including
      wastewater is required. The management should also include treated wastewater
      (TWW) reclamation and reuse, especially for agricultural irrigation. In Italy,
      TWW reuse is regulated by a quite restrictive approach (Ministry Decree, M.D.
      185/03), especially for some chemical compounds and microbiological parameters.
      The aim of the paper is the evaluation of TWW reuse potential in Sicily. A
      Geographic Information System (GIS) was built at regional level to quantify and
      locate the available TWW volumes. In particular, the characteristics of
      wastewater treatment plants (WWTPs) were integrated, through the GIS, with data
      on irrigation district areas. Moreover, in order to evaluate the Italian approach
      for reuse practice in agriculture, the water quality of different TWW effluents
      was analysed on the basis of both the Italian standards and the WHO guidelines.

PMID- 22592475
TI  - Enhanced removal of sodium salts supported by in-situ catalyst synthesis in a
      supercritical water oxidation process.
AB  - For practical applications of supercritical water oxidation to wastewater
      treatment, the deposition of inorganic salts in supercritical phase must be
      controlled to prevent a reactor from clogging. This study investigated enhanced
      removal of sodium salts with titanium particles, serving as a salt trapper and a
      catalyst precursor, and sodium recovery by sub-critical water. When Na(2)CO(3)
      was tested as a model salt, sodium removal efficiency was higher than
      theoretically maximum efficiency defined by Na(2)CO(3) solubility. The enhanced
      sodium removal resulted from in-situ synthesis of sodium titanate, which could
      catalyse acetic acid oxidation. The kinetics of sodium removal was described well
      by a diffusion mass-transfer model combined with a power law-type rate model of
      sodium titanate synthesis. Titanium particles showed positive effect on sodium
      removal in the case of NaOH, Na(2)SO(4) and Na(3)PO(4). However, they had
      negligible effect for NaCl and negative effect for Na(2)CrO(4), respectively.
      More than 99% of trapped sodium was recovered by sub-critical water except for
      Na(2)CrO(4). In contrast, sodium recovery efficiency remained less than 50% in
      the case of Na(2)CrO(4). Reused titanium particles showed the same performance
      for enhanced sodium removal. Enhanced salt removal supported by in-situ catalyst
      synthesis has great potential to enable both salt removal control and catalytic
      oxidation.

PMID- 22592476
TI  - Nutrient recovery from swine waste and protein biomass production using duckweed
      ponds (Landoltia punctata): southern Brazil.
AB  - Brazil is one of the most important countries in pork production worldwide,
      ranking third. This activity has an important role in the national economic
      scenario. However, the fast growth of this activity has caused major
      environmental impacts, especially in developing countries. The large amount of
      nitrogen and phosphorus compounds found in pig manure has caused ecological
      imbalances, with eutrophication of major river basins in the producing regions.
      Moreover, much of the pig production in developing countries occurs on small
      farms, and therefore causes diffuse pollution. Therefore, duckweed pond have been
      successfully used in the swine waste polishing, generating further a biomass with
      high protein content. The present study evaluated the efficiency of two full
      scale duckweed ponds for the polishing of a small pig farm effluent, biomass
      yield and crude protein (CP) content. Duckweed pond series received the effluent
      from a biodigester-storage pond, with a flow rate of 1 m(3)/day (chemical oxygen
      demand rate = 186 kg/ha day) produced by 300 animals. After 1 year a great
      improvement of effluent quality was observed, with removal of 96% of total
      Kjeldahl nitrogen (TKN) and 89% of total phosphorus (TP), on average. Nitrogen
      removal rate is one of the highest ever found (4.4 g TKN/m(2) day). Also, the
      dissolved oxygen rose from 0.0 to 3.0 mg/L. The two ponds produced together over
      13 tons of fresh biomass (90.5% moisture), with 35% of CP content, which
      represents a productivity of 24 tonsCP/ha year. Due to the high rate of nutrient
      removal, and also the high protein biomass production, duckweed ponds revealed,
      under the presented conditions, a great potential for the polishing and
      valorization of swine waste. Nevertheless, this technology should be better
      exploited to improve the sustainability of small pig farms in order to minimize
      the impacts of this activity on the environment.

PMID- 22592477
TI  - Evaluation of sampling methods for monitoring effluent phosphorus for on-site
      wastewater treatment systems.
AB  - More than 1,600 prefabricated on-site wastewater treatment plants are in
      operation in the Morsa watershed in Norway. As of 2010 a monitoring program on
      the performance of these plants is in effect. Sampling methods for wastewater
      treatment plants is discussed, and different methods are compared. The study
      includes six different plant models, of which all are prefabricated package
      plants. The parameters investigated were total phosphorus (Tot-P), orthophosphate
      (PO(4)-P) and suspended solids (SS). Diurnal curves showed no apparent repetitive
      variation over 24 h intervals, indicating good equalization and robust design to
      compensate for highly variable loadings. A comparison of grab samples and time
      proportional composite samples showed almost identical average values, and a
      paired two-tailed Student's t-test indicates no statistically significant
      difference between the sampling methods. The results indicate that equivalent
      results should be expected irrespective of sampling method, and, as composite
      sampling is attributed to much higher costs, it is recommended that grab sampling
      should be used when a large number of plants are evaluated.

PMID- 22592478
TI  - Adsorption of polyvinyl alcohol from wastewater by sintered porous red mud.
AB  - Several types of red mud-based porous materials (RMPM) and other raw minerals via
      different processes were prepared and characterized using X-ray diffraction (XRD)
      analyses and scanning electron microscope (SEM) observations. Using the polymer
      sponge method, a 72% apparent porosity could be reached compared with 64% by
      adding a pore-forming agent. These materials were tested for their adsorption of
      polyvinyl alcohol (PVA) from simulated textile wastewater. The best mass ratio of
      RMPM to PVA solution was 50:100 with a removal maximum of 25.8% after they were
      in contact for 50 min. The adsorption rate and kinetics could be better described
      by Lagergren's pseudo-second-order model in comparison with the pseudo-first
      order model.

PMID- 22592479
TI  - Experimental and CFD simulation studies of wall shear stress for different
      impeller configurations and MBR activated sludge.
AB  - Membrane bioreactors (MBRs) have been used successfully in biological wastewater
      treatment for effective solids-liquid separation. However, a common problem
      encountered with MBR systems is fouling of the membrane resulting in frequent
      membrane cleaning and replacement which makes the system less appealing for full
      scale applications. It has been widely demonstrated that the filtration
      performances in MBRs can be improved by understanding the shear stress over the
      membrane surface. Modern tools such as computational fluid dynamics (CFD) can be
      used to diagnose and understand the shear stress in an MBR. Nevertheless, proper
      experimental validation is required to validate CFD simulation. In this work
      experimental measurements of shear stress induced by impellers at a membrane
      surface were made with an electrochemical approach and the results were used to
      validate CFD simulations. As good results were obtained with the CFD model (<9%
      error), it was extrapolated to include the non-Newtonian behaviour of activated
      sludge.

PMID- 22592480
TI  - A framework of characteristics identification and source apportionment of water
      pollution in a river: a case study in the Jinjiang River, China.
AB  - A framework for characteristics identification and source apportionment of water
      pollution in the Jinjiang River of China was proposed in this study for
      evaluation. A total of 114 water samples which were generated between May 2009
      and September 2010 at 13 sites were collected and analysed. First, support vector
      machine (SVM) and water quality pollutant index (WQPI) were used for water
      quality comprehensive evaluation and identifying characteristic contaminants.
      Later, factor analysis with nonnegative constraints (FA-NNC) was employed for
      source apportionment. Finally, multi-linear regression of the absolute principal
      component score (APCS/MLR) was applied to further estimate source contributions
      for each characteristic contaminant. The results indicated that the water quality
      of the Jinjiang River was mainly at the third level (65.79%) based on national
      surface water quality permissible standards in China. Ammonia nitrogen, total
      phosphorus, mercury, iron and manganese were identified as characteristic
      contaminants. Source apportionment results showed that industrial activities
      (63.16%), agricultural non-point source (16.50%) and domestic sewage (12.85%)
      were the main anthropogenic pollution sources which were influencing the water
      quality of Jinjiang River. This proposed method provided a helpful framework for
      conducting water pollution management in aquatic environment.

PMID- 22592481
TI  - A novel combined electrochemical-magnetic method for water treatment.
AB  - Electrocoagulation (EC) is a wastewater treatment process in which aqueous
      pollutants can be removed by adsorption, entrapment, precipitation or coalescence
      during a coagulation step produced by electrochemically generated metallic
      species. When using Fe as the sacrificial electrode, Fe(2+) and Fe(3+) ions are
      formed. As Fe(3+) species are paramagnetic, this property can in principle be
      used to facilitate their removal through the application of a magnetic field. In
      the present work we present a proof-of-concept for a combined electrochemical
      magnetic method for pollutant removal. For this approach, the amounts of Fe(2+)
      and Fe(3+) produced in an EC cell at various voltages were measured by
      spectroscopic methods to confirm that Fe(3+) species predominate (up to 84%). The
      effectiveness of the presence of a magnetic field in the precipitation of
      coagulants from a suspension was confirmed by monitoring the turbidity change
      versus time with and without exposure to a magnetic field, up to a 30%
      improvement.

PMID- 22592482
TI  - Isolation and characterization of a heterotrophic nitrifier from coke plant
      wastewater.
AB  - This study investigated some factors affecting ammonium removal and nitrite
      accumulation by Alcaligenes faecalis C16, which was isolated from the activated
      sludge of a coking wastewater treatment plant. Nitrite was produced from ammonium
      only in the presence of citrate, acetate, meat extract, peptone or ethanol. The
      highest amount of nitrite was found with citrate as carbon source. A. faecalis
      C16 could not use glucose, fructose, sucrose and methanol. Under the optimum
      conditions of initial pH 6.0, C/N 14, 30  degrees C and 120 rpm, a maximum
      nitrite accumulation of 28.29 mg/L NO(2)(-)-N was achieved when the organism grew
      with citrate in four days. Nitrite accumulation increased with the increase of
      NH(4)(+)-N. Furthermore, A. faecalis C16 was shown to have phenol-degrading
      capacity during ammonium removal. Metabolism of phenol resulted in acidification
      of the media, which is not favorable for nitrification, whereas many other carbon
      sources made the medium more alkaline. However, no inhibitory effect by phenol
      was observed when phenol and acetate were used as mixed carbon source at
      different phenol/sodium acetate (P/S) ratios and their pH values were all
      controlled above 9.2 or P/S ratios below 5:5. These results suggested that A.
      faecalis C16 has some potential application in industrial wastewater treatment
      systems.

PMID- 22592485
TI  - Morphological assessment of the aortic valve using coronary computed tomography
      angiography, cardiovascular magnetic resonance, and transthoracic
      echocardiography: comparison with intraoperative findings.
AB  - To compare the diagnostic accuracies of coronary computed tomography angiography
      (CCTA), cardiovascular magnetic resonance (CMR), and transthoracic
      echocardiography (TTE) in aortic valve (AV) morphological assessments with
      operative findings. We retrospectively enrolled 262 patients who underwent CCTA,
      CMR, and TTE before AV surgery. Two independent blinded observers assessed AV
      morphology as being tricuspid, bicuspid, or quadricuspid using three imaging
      modalities. Interobserver and intermodality agreements were obtained with kappa
      statistics. The diagnostic accuracies of CCTA, CMR, and TTE for identifying AV
      morphology (tricuspid vs. non-tricuspid) were compared with intraoperative
      findings as the reference standard. At surgery, tricuspid AV, bicuspid AV, and
      quadricuspid AV were present in 179, 80, and 3 patients, respectively. The CCTA
      and CMR image qualities were all diagnostic. Thirteen cases of TTE were not
      evaluable due to severe AV calcification. An excellent correlation between CMR
      and CCTA was seen for the identification of AV morphology (kappa = 0.97). Good
      correlations existed between CCTA and TTE (kappa = 0.72) and between CMR and TTE
      (kappa = 0.74). CCTA, CMR, and TTE had an excellent or good interobserver
      agreement (kappa = 0.90, 0.95, and 0.72, respectively). Sensitivity, specificity,
      and positive and negative predictive values for AV morphology assessment
      (tricuspid vs. non-tricuspid) were: 97, 95, 98, and 94 % with CCTA (n = 262); 98,
      96, 98, and 95 % with CMR (n = 262); and 98, 88, 95, and 96 % with TTE (n = 249).
      CCTA and CMR are highly accurate for identifying AV morphology.

PMID- 22592483
TI  - Deciphering the Key Features of Malignant Tumor Microenvironment for Anti-cancer
      Therapy.
AB  - Tumor microenvironment (TME) is important in tumor development and may be a
      target for anti-cancer therapy. The genesis of TME is a dynamic process that is
      regulated by intrinsic and extrinsic factors and coordinated by multiple genes,
      cells, and signal pathways. Cancer anaerobic metabolism and various oncogenes may
      stimulate the genesis of TME. Tumor cells and cancer stem cells actively
      participate in the genesis of the cancer stem cell niche and tumor
      neovascularization, important in the initiation of the TME. Various cancer
      associated stromal cells, derived niche factors, and tumor-associated macrophages
      may function as promoters in the genesis of the TME. Dicer1 gene-deleted stromal
      cells can induce generation of cancer stem cells and initiate tumorigenesis,
      suggesting that stromal cells also may promote the genesis of the TME. Therefore,
      the key features of TME include niche-driving oncogenes, cancer anaerobic
      metabolism, niche-driving cancer stem cells, neovascularization, tumor-associated
      inflammatory cells, and cancer-associated stromal cells. These features are
      potential targets for normalization of the malignant TME and effective anti
      cancer therapy.

PMID- 22592487
TI  - Adenovirus:  an overview for pediatric infectious diseases specialists.

PMID- 22592486
TI  - Impact of HIV severity on cognitive and adaptive functioning during childhood and
      adolescence.
AB  - BACKGROUND: The influence of disease severity on cognitive and adaptive
      functioning in perinatally HIV-infected youth with (PHIV+/C) and without
      (PHIV+/NoC) a previous AIDS-defining illness (Centers for Disease Control and
      Prevention Class C event), compared with perinatally HIV-exposed but uninfected
      youth (PHEU) is not well understood. METHODS: This was a cross-sectional analysis
      of cognitive and adaptive functioning in PHIV+/C (n = 88), PHIV+/NoC (n = 270)
      and PHEU (n = 200) youth aged 7-16 years, from a multisite prospective cohort
      study. Youth and caregivers completed the Wechsler Intelligence Scale for
      Children, Fourth Edition and the Adaptive Behavior Assessment System, Second
      Edition, respectively. We compared means and rates of impairment between groups,
      and examined associations with other psychosocial factors. RESULTS: Overall mean
      scores on measures of cognitive and adaptive functioning were in the low average
      range for all 3 groups. After adjustment for covariates, mean full-scale
      intelligence quotient scores were significantly lower for the PHIV+/C group than
      the PHIV+/NoC and PHEU groups (mean = 77.8 versus 83.4 and 83.3, respectively),
      whereas no significant differences were observed between the PHEU and PHIV+/NoC
      groups in any domain. Lower cognitive performance for the PHIV+/C group was
      primarily attributable to a prior diagnosis of encephalopathy. No significant
      differences between groups were observed in adaptive functioning. CONCLUSION: For
      long-term survivors, youth with HIV infection and a prior Centers for Disease
      Control and Prevention Class C event have higher risk for cognitive but not
      adaptive impairment regardless of current health status; this finding appears
      attributable to a previous diagnosis of encephalopathy. Early preventive therapy
      may be critical in reducing risk of later neurodevelopmental impairments.

PMID- 22592488
TI  - Clinical prediction rules and pediatric infectious diseases.
AB  - Clinical prediction rules (CPR) are tools including appropriately weighted
      clinical aspects (history, physical examination and/or complementary tests)
      showing the odds for a specific diagnosis or prognosis. Their development
      includes a complex and strict process to achieve the scientific strength which
      supports use in clinical settings. Although CPR may be developed for almost any
      clinical situation, they are particularly useful in complex decision making, high
      risk situations and for health cost reduction. Most CPR in pediatrics are devoted
      to infectious diseases, but only a few of them are used in daily practice.
      Reluctance in using them may be related to the most pediatrician's expectation of
      100% sensitivity, when only a few CPR have sensitivity >90%. It is important to
      take into account that even a less-than-perfect CPR may be more sensitive than
      the physician's clinical judgment alone.

PMID- 22592489
TI  - Role of Trimethoprim-sulfamethoxazole for treatment of acute osteomyelitis in
      children.

PMID- 22592491
TI  - Antiviral treatment for children with influenza: what's the evidence?

PMID- 22592493
TI  - Denouement.

PMID- 22592494
TI  - The Pediatric Infectious Disease Journal newsletter.

PMID- 22592495
TI  - CD9 is expressed on human male germ cells that have a long-term repopulation
      potential after transplantation into mouse testes.
AB  - Human spermatogonial stem cells (SSCs) play critical roles in lifelong
      maintenance of male fertility and regeneration of spermatogenesis. These cells
      are expected to provide an important resource for male fertility preservation and
      restoration. A basic strategy has been proposed that would involve harvesting
      testis biopsy specimens from a cancer patient prior to cancer therapies, and
      transplanting them back to the patient at a later time; then, SSCs included in
      the specimens would regenerate spermatogenesis. To clinically apply this
      strategy, isolating live human SSCs is important. In this study, we investigated
      whether CD9, a known rodent SSC marker, is expressed on human male germ cells
      that can repopulate recipient mouse testes upon transplantation. Testicular
      tissues were obtained from men with obstructive azoospermia. Using
      immunohistochemistry, we found that CD9 was expressed in human male germ cells in
      the basal compartment of the seminiferous epithelium. Following immunomagnetic
      cell sorting, CD9-positive cells were enriched for germ cells expressing MAGEA4,
      which is expressed by spermatogonia and some early spermatocytes, compared with
      unsorted cells. We then transplanted CD9-positive cells into nude mouse testes
      and detected an approximately 3- to 4-fold enrichment of human germ cells that
      repopulated mouse testes for at least 4 mo after transplantation, compared with
      unsorted cells. We also observed that some cell turnover occurred in human germ
      cell colonies in recipient testes. These results demonstrate that CD9 identifies
      human male germ cells with capability of long-term survival and cell turnover in
      the xenogeneic testis environment.

PMID- 22592496
TI  - Expression of the ubiquitin proteasome system in neonatal rat gonocytes and
      spermatogonia: role in gonocyte differentiation.
AB  - The ubiquitin proteasome system (UPS) consists of a cascade of enzymatic
      reactions leading to the ubiquitination of proteins, with consequent degradation
      or altered functions of the proteins. Alterations in UPS genes have been
      associated with male infertility, suggesting the role of UPS in spermatogenesis.
      In the present study, we questioned whether UPS is involved in extensive
      remodeling and functional changes occurring during the differentiation of
      neonatal testicular gonocytes to spermatogonia, a step critical for the
      establishment of the spermatogonial stem cell population. We found that addition
      of the proteasome inhibitor lactacystin to isolated gonocytes inhibited their
      retinoic acid-induced differentiation in a dose-dependent manner, blocking the
      induction of the spermatogonial gene markers Stra8 and Dazl. We then compared the
      UPS gene expression profiles of Postnatal Day (PND) 3 gonocytes and PND8
      spermatogonia, using gene expression arrays and quantitative real-time PCR
      analyses. We identified 205 UPS genes, including 91 genes expressed at relatively
      high levels. From those, 28 genes were differentially expressed between gonocytes
      and spermatogonia. While ubiquitin-activating enzymes and ligases showed higher
      expression in gonocytes, most ubiquitin conjugating and deubiquitinating enzymes
      were expressed at higher levels in spermatogonia. Concomitant with the induction
      of spermatogonial gene markers, retinoic acid altered the expression of many UPS
      genes, suggesting that the UPS is remodeled during gonocyte differentiation. In
      conclusion, these studies identified novel ubiquitin-related genes in gonocytes
      and spermatogonia and revealed that proteasome function is involved in gonocyte
      differentiation. Considering the multiple roles of the UPS, it will be important
      to determine which UPS genes direct substrates to the proteasome and which are
      involved in proteasome-independent functions in gonocytes and to identify their
      target proteins.

PMID- 22592497
TI  - Gonadotropin-releasing hormone 1 directly affects corpora lutea lifespan in
      Mediterranean buffalo (Bubalus bubalis) during diestrus: presence and in vitro
      effects on enzymatic and hormonal activities.
AB  - The expression of gonadotropin-releasing hormone (GNRH) receptor (GNRHR) and the
      direct role of GNRH1 on corpora lutea function were studied in Mediterranean
      buffalo during diestrus. Immunohistochemistry evidenced at early, mid, and late
      luteal stages the presence of GNRHR only in large luteal cells and GNRH1 in both
      small and large luteal cells. Real-time PCR revealed GNRHR and GNRH1 mRNA at the
      three luteal stages, with lowest values in late corpora lutea. In vitro corpora
      lutea progesterone production was greater in mid stages and lesser in late luteal
      phases, whereas prostaglandin F2 alpha (PGF2alpha) increased from early to late
      stages, and PGE2 was greater in the earlier-luteal phase. Cyclooxygenase 1
      (prostaglandin-endoperoxide synthase 1; PTGS1) activity did not change during
      diestrus, whereas PTGS2 increased from early to late stages, and PGE2-9
      ketoreductase (PGE2-9-K) was greater in late corpora lutea. PTGS1 activity was
      greater than PTGS2 in early corpora lutea and lesser in late luteal phase. In
      corpora lutea cultured in vitro, the GNRH1 analog (buserelin) reduced
      progesterone secretion and increased PGF2alpha secretion as well as PTGS2 and
      PGE2-9-K activities at mid and late stages. PGE2 release and PTGS1 activity were
      increased by buserelin only in late corpora lutea. These results suggest that
      GNRH is expressed in all luteal cells of buffalo, whereas GNRHR is only expressed
      in large luteal phase. Additionally, GNRH directly down-regulates corpora lutea
      progesterone release, with the concomitant increases of PGF2alpha production and
      PTGS2 and PGE2-9-K enzymatic activities.

PMID- 22592498
TI  - Sexual harassment of girls in elementary school: a concealed phenomenon within a
      heterosexual romantic discourse.
AB  - The aim of this study was to enhance the understanding of young girls'
      experiences of peer sexual harassment in elementary school and of normalizing
      processes of school-related sexualized violence. Six focus group interviews with
      girls in Grade 1 through 6 were carried out in an elementary school in the
      northern part of Sweden. A content analyses showed that young girls experienced
      verbal, nonverbal, and sexual assault behaviors at school. Sexual harassment as a
      concealed phenomenon and manifest within a romantic discourse were themes found
      in the analysis. A conclusion is that schools have to acknowledge behaviors
      related to sexual harassment as a potential problem even in young ages and
      develop methods to approach the subject also for this age group.

PMID- 22592500
TI  - Spirituality and recovery from cardiac surgery: a review.
AB  - A large research literature attests to the positive influence of spirituality on
      a range of health outcomes. Recently, a growing literature links spirituality to
      improved recovery from cardiac surgery. Cardiac surgery has become an
      increasingly common procedure in the United States, so these results may provide
      a promising indication for improved treatment of patients undergoing surgery. To
      our knowledge, a comprehensive review of the literature in this area does not
      exist. Therefore, this paper reviews the literature relevant to the influence of
      spirituality on recovery from cardiac surgery. In addition, it proposes a
      conceptual model that attempts to explicate relationships among the variables
      studied in the research on this topic. Finally, it discusses limitations,
      suggests directions for future research, and discusses implications for the
      treatment of patients undergoing cardiac surgery.

PMID- 22592501
TI  - Comparative analysis of the chicken TCRalpha/delta locus.
AB  - The access to whole genome sequences has provided the opportunity to study the
      evolution and organization of immunologically related genes on a large scale. The
      genes encoding the T cell receptor (TCR) alpha and delta chains are part of a
      complex locus that has shown remarkable conserved organization across different
      amniote lineages. In this study we have examined and annotated the TCRalpha/delta
      locus in chicken (Gallus gallus) and compared it to that of zebra finch
      (Taeniopygia guttata) and other avian species using the current available genome
      data. We also analyzed the expressed chicken TCRalpha/delta transcript repertoire
      and compared it with that previously described for zebra finch. The analyses
      conducted in this study show that the TCRalpha/delta locus in birds has undergone
      major rearrangements and expansion of the germ line repertoire in chicken,
      compared to zebra finch. A major expansion of the chicken variable gene
      repertoire appears to be driven by selection for genes from a limited number of
      subgroups.

PMID- 22592502
TI  - Pharmacotherapeutic determinants for QTc interval prolongation in Japanese
      patients with mood disorder.
AB  - An increased incidence of sudden death has been observed among patients treated
      with antidepressants. A prolonged QTc interval is a known prognostic factor for
      fatal arrhythmia, and several studies have shown that the use of antidepressants
      can cause a prolonged QTc interval. However, few studies, especially in Japan,
      have compared the effects of multiple drugs on QTc interval or examined dose
      relationships in a clinical setting.We compared the effects of antidepressants on
      QT interval, corrected to QTc by Bazett's formula, in 729 Japanese patients who
      were diagnosed with mood disorder.Using stepwise multiple linear regression
      analysis, we found that the use of tricyclic antidepressants (P<0.01) and
      concomitant use of antipsychotics (P<0.05), as well as advanced age and being
      female (known factors for prolonged QTc interval; both P<0.01), significantly
      prolonged the QTc interval. Analysis of individual antidepressants also revealed
      that the use of clomipramine (P<0.01) and amitriptyline (P<0.05) significantly
      prolonged the QTc interval.Our results reveal that tricyclic antidepressants,
      especially clomipramine and amitriptyline, confer a risk of prolonged QTc
      interval in a dose-dependent manner. The selective serotonin reuptake inhibitors
      investigated (fluvoxamine, paroxetine, sertraline) were not indicated as risk
      factors for QTc prolongation.

PMID- 22592503
TI  - The antidepressant agomelatine in daily practice: results of the non
      interventional study VIVALDI.
AB  - The non-interventional study VIVALDI was carried out to evaluate the treatment
      with agomelatine, an innovative antidepressant, in routine practice.665
      psychiatrists treated 3 317 patients over 12 weeks with agomelatine and
      documented antidepressant effects via svMADRS, CGI scale and CircScreen
      questionnaire. Subgroups with severe depression (svMADRS >=30) and elderly
      patients (>=65 years) were also analyzed.In the total population, svMADRS total
      score decreased from 30.6 at baseline to 12.8 at final visit, in severely
      depressed patients from 36.7 to 14.7, in elderly patients from 29.0 to 12.2. In
      total 65.8% of patients could be classified as responders (>=50% decrease in
      svMADRS total score) and 54.8% as remitters (svMADRS <=12). Daytime sleepiness
      was ameliorated in 78.2% of patients. Adverse drug reactions were reported for
      10.0%, 8.9% and 10.1% of patients in total population, severely ill and elderly
      patients, respectively.In this study, the antidepressant effects, improvement of
      circadian rhythm disorders and good tolerability of agomelatine were observed in
      unselected depressed patients, including multimorbid elderly and severely
      depressed patients under routine practice.

PMID- 22592504
TI  - St John's wort (Hypericum perforatum) versus sertraline and placebo in major
      depressive disorder: continuation data from a 26-week RCT.
AB  - Hypericum perforatum (St John's wort: SJW) has been extensively studied as an
      antidepressant in short-term trials, however little research has been conducted
      on longer-term efficacy.Our objective was to analyze the continuation data from a
      26-week randomized, double-blind, controlled study of SJW (LI-160) vs. sertraline
      and placebo in major depressive disorder. 124 participant "responders" continued
      treatment after week 8, until week 26. They continued randomly assigned SJW (900
      1 500 mg), sertraline (50-100 mg) or matching placebo.At week 26, on the primary
      outcome, Hamilton depression rating scale (HAM-D) completer scores were: SJW
      (6.6+/-4.5), sertraline (7.1+/-5.4) and placebo (5.7+/-5.4) with a significant
      effect for time (p=0.036). Comparisons between all treatments were however non
      significant (p=0.61). This effect was mirrored on the other outcomes: the BDI,
      CGI-severity, CGI-improvement, and on intention-to-treat analyses.While the
      continuation data revealed an equivocal outcome between treatments at week 26,
      both SJW and sertraline were still therapeutically effective, with a pronounced
      "placebo-effect" impeding a significant result at week 26.

PMID- 22592505
TI  - Ziprasidone--not haloperidol--induces more de-novo neurogenesis of adult neural
      stem cells derived from murine hippocampus.
AB  - INTRODUCTION: Here, we present a stem-cell based study on the de-novo generation
      of beta-III-tubulin-positive neurons after treatment with the classic
      antipsychotic drug haloperidol or after treatment with the second-generation
      antipsychotic (SGA) ziprasidone. METHODS: Adult neural stem cells (ANSC)
      dissociated from the adult mouse hippocampus were expanded in cell culture with
      basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). ANSC
      differentiated upon withdrawal of EGF and bFGF. RESULTS AND DISCUSSION:
      Ziprasidone generated significantly more beta-III-tubulin-positive neurons than
      haloperidol during the differentiation of adult neural stem cells isolated from
      murine hippocampus (ANSC). We assume that this net increase in neurogenesis by
      ziprasidone relies on this drug's 5-HT1A receptor affinity, which is not present
      in the haloperidol molecule, since the inactivation by WAY100621 impeded this
      process. These data could possibly suggest a clinical relevance for studying
      antipsychotic drugs in the stem cell paradigm employed in this study.

PMID- 22592506
TI  - Efficacy and tolerability of switching to ziprasidone in italian patients with
      acute exacerbation of schizophrenia: an open-label trial.
AB  - The long-term maintenance of a stable condition is an important aim of
      schizophrenia therapy, which frequently requires the switch between 2
      antipsychotic agents. This 8-week multicenter study, conducted in Italy,
      evaluates the switch from a previous antipsychotic to ziprasidone.Adult acute
      schizophrenic patients requiring a change in antipsychotic for lack of efficacy
      or tolerability issues took ziprasidone 20 - 80 mg/bid. Dosages could be adjusted
      during the study. The primary efficacy outcomes were the differences in positive
      and negative syndrome scale (PANSS) and clinical global impression severity (CGI
      S) scores from baseline to study end. Other efficacy variables were clinical
      global impression improvement, global assessment of functioning, patient
      preference scale and drug attitude inventory.189 patients were evaluated; the
      mean (+/-SD) ziprasidone dose was 95.9+/-34.5 mg/day. PANSS and CGI-S scores
      significantly decreased throughout the study. All secondary outcomes
      significantly improved at the end of the study vs. baseline values. Ziprasidone
      was well tolerated; 13 patients reported a QTc prolongation (mild in 12
      patients).Notwithstanding the limitations of any non-comparative study, these
      results suggest that ziprasidone may be an effective and well-tolerated option in
      acute schizophrenia patients who discontinued a previous antipsychotic agent.

PMID- 22592507
TI  - Childhood Cancer Survivor Study participants' perceptions and knowledge of health
      insurance coverage: implications for the Affordable Care Act.
AB  - INTRODUCTION: Childhood cancer survivors face long-term health consequences, and
      comprehensive health insurance is critical. However, childhood cancer survivors
      may face barriers in accessing medical services due to being uninsured or
      underinsured. Little is known about the quality of survivors' health insurance
      coverage, and improving health insurance within the context of changes mandated
      by the 2010 Affordable Care Act requires understanding survivors' coverage. The
      current study explored adult childhood cancer survivors' quality of health
      insurance coverage. METHODS: From 9/09 to 2/10, we conducted in-depth,
      semistructured qualitative interviews with 39 adult participants from the
      Childhood Cancer Survivor Study, a cohort of 5-year survivors of cancers
      diagnosed before age 21. Interviews were recorded and transcribed; content
      analyses were conducted by two coders (kappa = 0.88) using NVivo 8. RESULTS: Most
      insured survivors reported satisfaction with the quality of their coverage;
      however, they expressed low expectations. Almost half reported annual out-of
      pocket costs exceeding $2,000, yet most felt fortunate to simply have coverage.
      One third of insured survivors had difficulty obtaining coverage, and many had
      difficulties understanding how to utilize it. Most uninsured survivors minimized
      their need for care. Worry about future health care costs seemed inevitable among
      insured and uninsured survivors. Almost all participants lacked knowledge about
      existing health insurance-related laws. CONCLUSIONS AND IMPLICATIONS FOR CANCER
      SURVIVORS: Insured survivors had low coverage expectations, and uninsured
      survivors avoided care. Childhood cancer survivors will likely benefit from
      assistance in how to access and utilize the new health care reform provisions
      (e.g., Medicaid expansion, expansion of parents' insurance, and mandatory primary
      care coverage).

PMID- 22592508
TI  - Combination treatment with aripiprazole and valproic acid for acute mania: an 8
      week, single-blind, randomized controlled trial.
AB  - OBJECTIVES: Despite the fact that combination treatment for patients with acute
      bipolar is prevalent in clinical practice, the outcomes of adjunct treatment with
      aripiprazole and a mood stabilizer have rarely been reported. The aim of this
      single-blind, randomized, controlled trial was to investigate treatment efficacy
      and safety of aripiprazole as an adjunct to valproic acid (Ari+Val), compared
      with haloperidol plus valproic acid (Hal+Val), in acute manic patients. METHODS:
      Treatment efficacy was prospectively assessed for 8 weeks in 42 patients with
      acute mania using the Young Mania Rating Scale and the Clinical Global Impression
      Severity of illness scale. Emergent adverse events were assessed by the Drug
      Induced Extrapyramidal Symptoms Scale and the Liverpool University Neuroleptic
      Side Effect Rating Scale. RESULTS: Both Ari+Val and Hal+Val produced a high rate
      of response (85.7% and 92.9%, respectively) and remission (82.1% and 85.7%,
      respectively) after the 8-week trial. Changes in the Young Mania Rating Scale and
      the Clinical Global Impression-Severity of illness scale over the study period
      and time to remission and response were not significantly different between the 2
      groups. Patients treated with Ari+Val showed significantly fewer extrapyramidal
      adverse events than those treated with Hal+Val (t = -2.048, F = 40, P = 0.048).
      However, significant weight gain was more prevalent in the Ari+Val group than the
      Hal+Val group (t = 2.055, F = 40, P = 0.046). CONCLUSIONS: Our findings suggest
      that both combination strategies with Ari+Val and Hal+Val are beneficial for
      acute manic episode. Although patients receiving Ari+Val showed fewer
      extrapyramidal symptoms than those taking Hal+Val, careful consideration of
      adverse events such as weight gain and sedation is warranted.

PMID- 22592509
TI  - Selegiline:  a reappraisal of its role in Parkinson disease.
AB  - Selegiline at the doses used in Parkinson disease is a selective irreversible
      monoamine oxidase type B inhibitor, which potentiates dopaminergic function in
      the brain, and is used as monotherapy in early Parkinson disease or in
      combination with levodopa in more advanced disease. A renewed interest in
      monoamine oxidase type B inhibitors in the treatment of Parkinson disease has
      emerged after recent clinical trials of agents in this class. The use of
      selegiline monotherapy in early Parkinson disease is supported by the results of
      a large well-controlled trial in 800 patients (DATATOP) and several other
      studies, which demonstrated a symptomatic benefit, a reduction in disability, and
      a delay in the need to start levodopa therapy. Administered with levodopa in
      studies of up to 5 years' duration in patients with more advanced disease,
      selegiline improved disease-related disability, reduced the end-of-dose motor
      fluctuations, and also led to a reduction of the dose and dose frequency of
      levodopa required.Selegiline was the first drug to be investigated as a possible
      neuroprotective agent in patients with Parkinson disease, based on preclinical
      studies indicating protection of dopaminergic neurons from damage. The results of
      the extensive body of clinical trials, including delayed and lower levodopa
      requirements, may indeed suggest that selegiline, in addition to conferring
      symptomatic benefit, may have other effects on disease progression. Selegiline is
      well tolerated, and initial fears of increased mortality with the drug have not
      been borne out by subsequent robust meta-analyses.

PMID- 22592510
TI  - Atypical antipsychotic drugs, schizophrenia, and metabolic syndrome in non-Euro
      American societies.
AB  - OBJECTIVE: There has been an increase in the European and North American
      schizophrenia literature discussing the high prevalence of metabolic syndrome
      induced by atypical antipsychotic agents. The aim of this article was to review
      available data on metabolic syndrome induced by atypical antipsychotic agents in
      patients with schizophrenia or schizoaffective disorders selected from societies
      different from European and North American ones (termed non-Euro-American
      societies [NEAS]). METHODS: A review of the literature published via MedLine
      between 1975 and July 2011 was consulted. Terms used for the search were "glucose
      intolerance, metabolic syndrome, insulin resistance, weight gain, dyslipidemia"
      in association with "atypical antipsychotic drugs, second generation
      antipsychotics, risperidone, olanzapine, aripiprazole, ziprasidone, quetiapine,
      clozapine, zotepine, perospirone, paliperidone, iloperidone, asenapine,
      amisulpride, lurasidone." RESULTS: Prospective studies selecting patients from
      NEAS show that olanzapine poses the highest metabolic syndrome incidence.
      Clozapine poses the highest prevalence of this syndrome. In NEAS, the prevalence
      of this syndrome ranges from 14.7% to 69.3%. The incidence could be considered as
      20% (according to the International Diabetes Federation criteria) after 1 year of
      treatment with an atypical antipsychotic drug. Female sex, older age, and high
      body mass index seem to be the most frequent risk factor mentioned. A possible
      stratification of the risk of metabolic syndrome in patients with schizophrenia
      receiving atypical antipsychotic drugs is as follows: Minimal-risk societies are
      constituted by societies living in Eastern Asian countries, whereas intermediate
      risk societies are constituted by societies living in Western Asia and South
      America, and high-risk societies are societies living in Australia. CONCLUSION:
      The metabolic syndrome development profile in patients with schizophrenia
      receiving atypical antipsychotic drugs in NEAS seems to be comparable to that in
      European and North American societies, especially when, among NEAS, high-risk
      societies are concerned. Comparative controlled studies are needed for a better
      comprehension of this adverse drug effect between both types of societies.

PMID- 22592511
TI  - Lacosamide in Lennox-Gastaut syndrome: case report.
AB  - INTRODUCTION: Lennox Gastaut syndrome (LGS) is an epileptic encephalopathy
      characterized by tonic, atonic, and atypical absence seizures usually refractory
      to pharmacological treatment. Patients generally continue with seizures despite
      treatment with the commercially available antiepileptic drugs (AEDs). Lacosamide
      (LCM) is a new AED recently approved for treatment of partial onset seizures with
      or without secondary generalization. Lacosamide has a novel mechanism of action
      that seems to be different in relation to other conventional AEDs. OBJECTIVE: To
      report LCM-caused worsening of tonic seizures and electroencephalographic pattern
      in a patient with Lennox-Gastaut syndrome. CASE REPORT: We report the evolution
      of a patient with LGS resistant to several AEDs with a cryptogenic hepatopathy in
      whom LCM caused worsening of tonic seizures and electroencephalographic pattern.
      Once LCM was discontinued, the patient returned to his clinical and electrical
      baseline. CONCLUSION: Lennox Gastaut syndrome may exacerbate tonic seizures and
      electrical pattern of patients with LGS.

PMID- 22592512
TI  - Lithium citrate as treatment of Canavan disease.
AB  - Canavan disease is a rare autosomal recessive leukodystrophy characterized by
      abnormal accumulation of N-acetyl aspartate (NAA) in brain white matter.
      Currently, there is no cure for this disease, and management of patients consists
      mainly of treating symptoms. We describe a 3-month-old girl who was hospitalized
      for poor head control and decreased muscle tone. A battery of laboratory and
      genetic (homozygous mutation p.C218X) analysis revealed the presence of Canavan
      disease. Lithium citrate was initiated at a dosage of 45 mg/kg per day after
      diagnosis. Periodic controls of thyroid and liver function, and lithium levels in
      blood showed that this drug was sure and well tolerated. After 1 year of
      treatment, NAA levels decreased by approximately 20% in the brain region, urinary
      NAA levels showed a reduction of 80%, and patient improved alertness and visual
      tracking but continued with no heat support, axial hypotonia, and spastic
      diplegia. In our patient, the results obtained after drug administration are
      important with respect to the decrease in NAA and more discreet in clinical
      improvement. However, given the absence of adverse effects and limited treatment
      options, lithium citrate may be a good alternative to stop the progression of the
      disease and improve the quality of life of patients.

PMID- 22592513
TI  - Tridentate ligands and beyond in group IV metal alpha-olefin homo-/co
      polymerization catalysis.
AB  - The opening up of new markets, particularly in the Far East, is expected to
      increase the industrial demand for more (and new) plastic materials. In turn,
      this will drive the need for further catalyst development, with increased
      efficiency and with the capacity to easily control the resulting polymer
      properties being high on the agenda. With this in mind, tailoring the pre
      catalyst structure has proved to be a very successful strategy, and has allowed
      for the elucidation of a number of structure-activity trends. A particularly
      fruitful synthetic avenue has been the deployment of multi-dentate ancillary
      ligands bearing one or more substituents containing additional functionality,
      capable of weakly binding to the metal. Such a method is versatile and allows for
      the incorporation of a wide range of functionality. Furthermore, benefits of such
      an approach include the ability to control the % incorporation of co-monomers, in
      situ screening, low co-catalyst loadings (versus activity enhancement) as well as
      control over the resultant polymer structure. This review underlines the efforts
      made in the last few years with regard to the use of tridentate ligands and
      beyond in the field of alpha-olefin polymerization using catalytic systems based
      on group IV metals.

PMID- 22592514
TI  - Ventricular muscarinic receptor remodeling in patients with and without primary
      ventricular fibrillation. An imaging study.
AB  - BACKGROUND: Vagal innervation modulates the electrical stability of the left
      ventricle (LV) during ischemia. Thus, abnormal parasympathetic activity in
      myocardial infarction (MI) patients with primary ventricular fibrillation (FV)
      can account for their arrhythmic disorders. We evaluated LV muscarinic receptor
      density (B (max)) after MI in patients with (FV(G), n = 11) or without (nFV(G), n
      = 12) primary FV. METHODS AND RESULTS: The B (max) was measured by positron
      emission tomography and the specific antagonist [(11)C]methylquinuclidinyl
      benzilate ([(11)C]MQNB) in 23 patients 39 +/- 19 days post-MI, and 10 volunteers.
      Myocardial damage was quantified by delayed contrast-enhanced magnetic resonance
      imaging. Three short-axis slices per subject were analyzed and six time-activity
      curves per slice were fitted to a 3-compartment ligand-receptor model. The B
      (max) in remote regions of the 23 patients (67 +/- 36 pmol/mL . tissue; n = 139)
      was higher than in normal regions of volunteers (33 +/- 16 pmol/mL . tissue; n =
      171; P = .01). Receptor density in remote regions was similarly upregulated in
      nFV(G) (69 +/- 31 pmol/mL . tissue, n = 73) and FV(G) (66 +/- 40 pmol/mL .
      tissue, n = 66; P = .72). In damaged regions, the B (max) was reduced in both
      patient groups (44 pmol/mL . tissue). CONCLUSIONS: Chronically infarcted patients
      with or without primary FV share similar patterns of ventricular muscarinic
      receptor remodeling, characterized by receptor upregulation, in remote non
      damaged territories.

PMID- 22592515
TI  - Role of procalcitonin in the diagnosis of severe infection in pediatric patients
      with fever and Neutropenia--a systemic review and meta-analysis.
AB  - OBJECTIVE: The aim of this study was to determine the accuracy of the
      procalcitonin (PCT) test for diagnosis of bacterial sepsis in pediatric cancer
      patients with febrile neutropenia. METHODS: Three major databases, MEDLINE,
      EMBASE and the Cochrane Library were searched for studies that evaluated the
      diagnostic value of PCT alone or compared with other laboratory markers such as C
      reactive protein (CRP) to identify bacterial sepsis in children with fever and
      neutropenia. A bivariate model was used to derive summary sensitivity and
      specificity of the diagnostic tests. RESULTS: A total of 10 studies looking into
      PCT tests and 8 studies looking into CRP tests were included in the final
      analysis. The prevalence of bacterial sepsis was 304 of 1031 (29.5%) in PCT
      studies and 741 of 1316 (56.3%) in CRP studies. In terms of area under the
      receiver operating characteristic curve, PCT had comparable discrimination to CRP
      (area under the curve: 0.75 versus 0.74). PCT was not as sensitive as the CRP
      test. The pooled sensitivity of PCT was 0.59 (95% confidence interval [CI]: 0.42
      0.74) as compared with 0.75 (95% CI: 0.61-0.85) for CRP. PCT was more specific
      than sensitive whereas CRP was more sensitive than specific in this population.
      The pooled specificity was 0.76 (95% CI: 0.64-0.85) for PCT and 0.62 (95% CI:
      0.49-0.73) for CRP. PCT had greater likelihood ratio positive (2.50; 95% CI: 1.64
      3.81), making it the better rule-in test. CONCLUSIONS: Of three markers
      potentially useful for diagnosing bacterial sepsis in children with fever and
      neutropenia, PCT had comparable diagnostic accuracy to CRP.

PMID- 22592516
TI  - HIV and Hepatitis B coinfection among perinatally HIV-infected Thai adolescents.
AB  - OBJECTIVES: This study aimed to determine the prevalence of hepatitis B virus
      (HBV) coinfection and HBV seropositivity in perinatally HIV-infected adolescents.
      A secondary objective was to describe the clinical characteristics of adolescents
      with chronic HBV/HIV coinfection. MATERIALS AND METHODS: Multicenter cross
      sectional study of perinatally HIV-infected adolescents aged 12-25 years. HBV
      surface antigen, surface antibody (anti-HBs) and core antibody (anti-HBc) were
      measured. Coinfection was defined as having persistently positive HBV surface
      antigen. Seroprotective antibody from immunization was defined as having anti-HBs
      >=10 mIU/mL with negative anti-HBc. HBV DNA quantitation and rtM204V/I mutation
      analysis (lamivudine resistance-associated mutation) were performed in
      adolescents with chronic HBV infection. RESULTS: From November 2010 to March
      2011, 521 patients were enrolled. Mean (SD) of CD4 lymphocyte count was 685 (324)
      cells/MUL. The prevalence of HBV/HIV coinfection was 3.3% (95% confidence
      interval: 1.9-5.2%). Protective antibody against HBV was found in 18% of
      population, and this was significantly higher among adolescents who received than
      those who did not receive HBV revaccination after receiving antiretroviral
      therapy (93% versus 6%, P < 0.01). Among adolescents with chronic HBV infection,
      88% have received lamivudine; however, 69% have HBV DNA >10 copies/mL and 75% had
      the rtM204V/I mutation. CONCLUSIONS: The prevalence of HBV coinfection in HIV
      infected Thai adolescents was 3.3%. Most HIV-infected adolescents had no HBV
      protective antibody; therefore, revaccination with HBV vaccine is encouraged. The
      high prevalence of HBV-lamivudine resistance underscores the importance of HBV
      screening prior to antiretroviral therapy initiation to guide the selection of
      optimal regimen for coinfected children.

PMID- 22592517
TI  - Treatment complications in children with lyme meningitis.
AB  - BACKGROUND: The rate and type of treatment complications in children treated for
      Lyme meningitis have not been described. METHODS: We performed a retrospective
      cohort study of children with Lyme meningitis who presented to 1 of 3 emergency
      departments located in Lyme disease endemic areas between 1997 and 2010. We
      defined a case of Lyme meningitis as a child with cerebrospinal fluid pleocytosis
      and either positive Lyme serology or an erythema migrans rash. We identified
      prescribed treatment and reasons for all return visits. Our primary outcome was
      the presence of any treatment complication within 30 days of diagnosis. RESULTS:
      We identified 157 patients with Lyme meningitis with a median age of 10 years
      (interquartile range: 7-13 years). Of the 149 children with Lyme meningitis and
      available follow-up records, 39 (26%) had 1 or more complications, and 21 (14%)
      required a change in prescribed antibiotic therapy. The median time for
      developing the first complication was 11 days (interquartile range: 9-14 days).
      Ten percent of the patients had an adverse drug reaction. Of the 144 children who
      had a peripherally inserted central catheter placed, 25 (17%) had at least 1
      peripherally inserted central catheter-associated complication: 14 (10%) had a
      mechanical problem, 11 (8%) had an infectious complication and 1 (1%) had a
      venous thromboembolism. CONCLUSIONS: As current Lyme meningitis treatment
      regimens have substantial associated morbidity, future research should
      investigate the efficacy of alternate regimens.

PMID- 22592518
TI  - Hearing in preterm infants with postnatally acquired cytomegalovirus infection.
AB  - Cytomegalovirus is an important cause of sensorineural hearing loss in children.
      In contrast to congenitally infected infants, little is known about hearing in
      preterm infants with postnatal cytomegalovirus infection. We studied the hearing
      in 64 preterm infants during the first year of life and in 18 during the second
      year of life. None of the infants developed sensorineural hearing loss.

PMID- 22592519
TI  - Tympanometry in discrimination of otoscopic diagnoses in young ambulatory
      children.
AB  - BACKGROUND: Tympanometry can indicate middle ear effusion in children referred
      for tympanostomy tube placement. In outpatient setting, objective adjunctive
      tools are needed to diagnose the otitis media spectrum. METHODS: We enrolled and
      followed 515 children aged 6-35 months at primary care level. We compared
      tympanometry with pneumatic otoscopy and evaluated the proportions of type A, C1,
      C2, Cs and B tympanograms in relation to specific otoscopic diagnoses in 2206 and
      1006 examinations at symptomatic and asymptomatic visits, respectively. RESULTS:
      At symptomatic visits, different peaked tympanograms were associated with a
      healthy middle ear as follows: type A in 78%, type C1 in 62%, type C2 in 54% and
      type Cs in 18% of examinations. In contrast, any peaked tympanogram was related
      to healthy middle ear in 67% of examinations. Flat (type B) tympanogram was
      related to otitis media with effusion in 44% and to acute otitis media in 56% of
      examinations, respectively. At asymptomatic visits, the peaked tympanograms
      together were associated with a healthy middle ear in 87% of otoscopic
      examinations. Flat tympanogram indicated otitis media with effusion as well in
      87% of examinations. CONCLUSIONS: Tympanometry is not a useful tool in detecting
      specific otoscopic diagnoses because it cannot distinguish between otitis media
      with effusion and acute otitis media. However, among outpatients all peaked
      tympanograms suggest a healthy middle ear and a flat tympanogram is useful in
      detecting any middle ear effusion. Thus, tympanometry can be used as an
      adjunctive tool, but accurate diagnosis requires careful pneumatic otoscopy.

PMID- 22592520
TI  - Acoustic reflectometry in discrimination of otoscopic diagnoses in young
      ambulatory children.
AB  - BACKGROUND: Studies concerning spectral gradient acoustic reflectometry (SG-AR)
      have analyzed middle ear effusion only as 1 entity. The usefulness of SG-AR to
      detect specific otoscopic diagnoses of otitis media in young children is unknown.
      METHODS: Among 515 children aged 6-35 months, we compared SG-AR with pneumatic
      otoscopy and evaluated the proportions of 5 manufacturer-recommended SG-AR levels
      in relation to specific otoscopic diagnoses in 2802 and 1240 examinations at
      symptomatic and asymptomatic visits, respectively. RESULTS: At symptomatic
      visits, when the angle value was >95 degrees  (level 1), healthy middle ear was
      diagnosed in 76% of otoscopic examinations and acute otitis media in 5%. Levels 2
      (70-95 degrees ) and 3 (60-69 degrees ) did not relate to any otoscopic
      diagnosis. Levels 4 and 5 associated with acute otitis media in 50% and 64%, and
      otitis media with effusion in 33% and 32% of examinations, respectively. At
      asymptomatic visits, levels 1, 2 and 3 were associated with healthy middle ear in
      87%, 71% and 54% of examinations, respectively. With levels 4 and 5, otitis media
      with effusion was diagnosed in 62% and 79% of examinations, respectively.
      CONCLUSIONS: SG-AR is not useful in making specific otoscopic diagnoses. Although
      the extremities of 5 SG-AR levels are able to differentiate ears with and without
      effusion, SG-AR is not able to differentiate acute otitis media from otitis media
      with effusion. Therefore, SG-AR can aid in diagnostics, but careful pneumatic
      otoscopy is needed to determine accurate diagnoses.

PMID- 22592521
TI  - The impact of the heptavalent pneumococcal conjugate vaccine on risk factors for
      Streptococcus pneumoniae carriage in children.
AB  - BACKGROUND: The aim of the study was to investigate whether the 7-valent
      pneumococcal conjugate vaccine (PCV7) alters common risk factors of
      nasopharyngeal carriage by Streptococcus pneumoniae in children. METHODS: From
      July 2005 through December 2010, we performed a cross-sectional study
      investigating risk factors associated with pneumococcal carriage in children.
      Parents of participating children completed questionnaires including whether or
      not the children received PCV7 vaccination. RESULTS: Among 9705 children, 20.2%
      of them received at least 1 dose of the PCV7 vaccine. Multivariate logistic
      regression models identified older age, having 1 sibling in a family, history of
      acute otitis media and household exposure to smoking as independent risk factors
      for pneumococcal carriage in the unvaccinated group, but not associated with
      pneumococcal carriage in the vaccinated group. The number of siblings >=2 in a
      family, history of upper respiratory tract infection and child-care attendance
      were strong factors associated with pneumococcal carriage in children, regardless
      of vaccination. In vaccinated group, breast-feeding was associated with increased
      nonvaccine type pneumococcal carriage, mainly in children with upper respiratory
      tract infection. CONCLUSIONS: PCV7 decreased the association between pneumococcal
      carriage and older age, 1 sibling in a family, history of acute otitis media and
      household exposure to smoking, but increased the association between pneumococcal
      carriage and breast-feeding.

PMID- 22592522
TI  - Association of celiac disease genes with inflammatory bowel disease in Finnish
      and Swedish patients.
AB  - Some genetic loci may affect susceptibility to multiple immune system-related
      diseases. In the current study, we investigated whether the known susceptibility
      loci for celiac disease (CelD) also associate with Crohn's disease (CD) and/or
      ulcerative colitis (UC), the two main forms of inflammatory bowel disease (IBD),
      in Finnish patients. A total of 45 genetic markers were genotyped in a Finnish
      data set comprising 699 IBD patients and 2482 controls. Single-marker association
      with IBD and its subphenotypes was tested. A meta-analysis with a Swedish UC data
      set was also performed. A total of 12 single-nucleotide polymorphisms associated
      with CD and/or UC (P<0.05). In the subphenotype analysis, rs6974491-ELMO1
      (P=0.0002, odds ratio (OR): 2.20) and rs2298428-UBE2L3 (P=5.44 * 10(-5), OR:
      2.59) associated with pediatric UC and CD, respectively. In the meta-analysis,
      rs4819388-ICOSLG (P=0.00042, OR: 0.79) associated with UC. In the subphenotype
      meta-analysis, rs1738074-TAGAP (P=7.40 * 10(-5), OR: 0.61), rs6974491-ELMO1
      (P=0.00052, OR: 1.73) and rs4819388-ICOSLG (P=0.00019, OR: 0.75) associated with
      familial UC, pediatric UC and sporadic UC, respectively. Multiple CelD risk loci
      also confer susceptibility for CD and/or UC in the Finnish and Swedish
      populations. Certain genetic risk variants may furthermore predispose an
      individual for developing a particular disease phenotype.

PMID- 22592523
TI  - Human B-cell ontogeny in humanized NOD/SCID gammac(null) mice generates a diverse
      yet auto/poly- and HIV-1-reactive antibody repertoire.
AB  - Characterization of the human antibody (Ab) repertoire in mouse models of the
      human immune system is essential to establish their relevance in translational
      studies. Single human B cells were sorted from bone marrow and periphery of
      humanized NOD/SCID gammac(null) (hNSG) mice at 8-10 months post engraftment with
      human cord blood-derived CD34(+) stem cells. Human IG variable heavy (V(H)) and
      kappa (V(kappa)) genes were amplified, cognate V(H)-V(kappa) gene-pairs assembled
      as single-chain variable fragment-Fc Abs (scFvFcs) and functional studies were
      performed. Although overall distribution of V(H) genes approximated the normal
      human Ab repertoire, analysis of the V(H)-third complementarity-determining
      regions in the mature B-cell subset demonstrated an increase in length and
      positive charges, suggesting autoimmune characteristics. Additionally, >70% of
      V(kappa) sequences utilized V(kappa)4-1, a germline gene associated with
      autoimmunity. The mature B-cell subset-derived scFvFcs displayed the highest
      frequency of autoreactivity and polyspecificity, suggesting defects in checkpoint
      control mechanisms. Furthermore, these scFvFcs demonstrated binding to
      recombinant HIV envelope corroborating previous observations of
      poly/autoreactivity in anti-HIVgp140 Abs. These data lend support to the
      hypothesis that anti-HIV broadly neutralizing antibodies may be derived from
      auto/polyspecific Abs that escaped immune elimination and that the hNSG mouse
      could provide a new experimental platform for studying the origin of anti-HIV
      neutralizing Ab responses.

PMID- 22592525
TI  - Anchoring and scaffolding: V(1)-ATPase interactions with widespread implications.

PMID- 22592524
TI  - A review of time courses and predictors of lipid changes with fenofibric acid
      statin combination.
AB  - Fibrates activate peroxisome proliferator activated receptor alpha and exert
      beneficial effects on triglycerides, high-density lipoprotein cholesterol, and
      low density lipoprotein subspecies. Fenofibric acid (FA) has been studied in a
      large number of patients with mixed dyslipidemia, combined with a low- or
      moderate-dose statin. The combination of FA with simvastatin, atorvastatin and
      rosuvastatin resulted in greater improvement of the overall lipid profile
      compared with the corresponding statin dose. The long-term efficacy of FA
      combined with low- or moderate- dose statin has been demonstrated in a wide range
      of patients, including patients with type 2 diabetes mellitus, metabolic
      syndrome, or elderly subjects. The FA and statin combination seems to be a
      reasonable option to further reduce cardiovascular risk in high-risk populations,
      although trials examining cardiovascular disease events are missing.

PMID- 22592526
TI  - Tumor suppressor function of the polycomb group genes.

PMID- 22592527
TI  - Preferential killing of p53-deficient cancer cells by reversine.
AB  - Reversine is a small synthetic molecule that inhibits multiple mitotic kinases,
      including MPS1 as well as Aurora kinase A and B (AURKA and AURKB). Here, we
      investigated the effects of reversine on p53-deficient vs p53-proficient cancer
      cells. We found that low doses (~0.5 uM) of reversine, which selectively inhibit
      MPS1 and hence impair the spindle assembly checkpoint, kill human TP53 (-/-) 
      colon carcinoma cells less efficiently than their wild-type counterparts. In
      sharp contrast, high doses (~5 uM) of reversine induced hyperploidization and
      apoptosis to a much larger extent in TP53 (-/-)  than in TP53 (+/+)  cells. Such
      a selective cytotoxicity could not be reproduced by the knockdown of MPS1, AURKA
      and AURKB, neither alone nor in combination, suggesting that it involves multiple
      (rather than a few) molecular targets of reversine. Videomicroscopy-based cell
      fate profiling revealed that, in response to high-dose reversine, TP53 (-/-) 
      (but not TP53 (+/+) ) cells undergo several consecutive rounds of abortive
      mitosis, resulting in the generation of hyperpolyploid cells that are prone to
      succumb to apoptosis upon the activation of mitotic catastrophe. In line with
      this notion, the depletion of anti-apoptotic proteins of the BCL-2 family
      sensitized TP53 (-/-)  cells to the toxic effects of high-dose reversine.
      Moreover, the knockdown of BAX or APAF-1, as well as the chemical inhibition of
      caspases, limited the death of TP53 (-/-)  cells in response to high-dose
      reversine. Altogether, these results suggest that p53-deficient cells are
      particularly sensitive to the simultaneous inhibition of multiple kinases,
      including MPS1, as it occurs in response to high-dose reversine.

PMID- 22592528
TI  - E2F1-dependent methyl cap formation requires RNA pol II phosphorylation.
AB  - Gene expression is a process integral to cell proliferation. The E2F family of
      transcription factors upregulates expression of transcripts whose products are
      essential for cell cycle progression. Here, we report that E2F1 promotes gene
      expression by an additional mechanism, that is, formation of the methyl cap on
      RNA pol II transcripts. The methyl cap is required for mRNA maturation,
      expression and stability. We demonstrate that E2F1 increases RNA pol II
      phosphorylation, which promotes recruitment of the methyl cap synthetic enzymes.
      Upregulation of RNA pol II phosphorylation is required for E2F1-dependent methyl
      cap formation.

PMID- 22592529
TI  - Phosphorylation by cyclin-dependent kinase-9 controls ubiquitin-conjugating
      enzyme-2A function.
AB  - Cyclin-dependent kinase-9 (CDK9) plays a central role in transcriptional
      elongation and controls multiple cotranscriptional histone modifications,
      including histone H2B monoubiquitination (H2Bub1). Like other CDK9-dependent
      histone modifications, the role of CDK9 in maintaining H2Bub1 was shown to be
      partially dependent upon the phosphorylation status of Ser2 of the RNA polymerase
      II (RNAPII) C-terminal domain (CTD). Since mutation of Ser2 within the RNAPII CTD
      resulted in a milder effect on H2Bub1 compared with CDK9 knockdown, we explored
      whether another CDK9 target may also influence H2Bub1. Based on its homology to
      yeast Bur1, we hypothesized that CDK9 may directly phosphorylate and activate the
      ubiquitin-conjugating enzyme utilized for H2B monoubiquitination. Indeed, we
      demonstrate that UBE2A specifically interacts with CDK9, but not CDK2.
      Furthermore, UBE2A is phosphorylated by CDK9 in vitro and increases UBE2A
      activity. Interestingly, CDK9 knockdown not only decreases UBE2A phosphorylation
      and H2Bub1, but also significantly impairs the induction of UBE2A-dependent
      monoubiquitination of proliferating cell nuclear antigen (PCNA). Thus, we provide
      the first evidence that CDK9 is required for the activity of UBE2A in humans, and
      that its activity is not only required for maintaining H2Bub1, but also for the
      monoubiquitination of PCNA. The common involvement of these two ubiquitinations
      in distinct DNA repair pathways may provide a mechanistic rationale for further
      exploring CDK9 as a combinatorial target for increasing the efficacy of existing
      cancer therapies based on the induction of DNA damage and are repaired by
      mechanisms which require H2Bub1 and/or PCNA ubiquitination.

PMID- 22592530
TI  - Structure of monoubiquitinated PCNA: implications for DNA polymerase switching
      and Okazaki fragment maturation.
AB  - Ubiquitination of proliferating cell nuclear antigen (PCNA) to ub-PCNA is
      essential for DNA replication across bulky template lesions caused by UV
      radiation and alkylating agents, as ub-PCNA orchestrates the recruitment and
      switching of translesion synthesis (TLS) polymerases with replication
      polymerases. This allows replication to proceed, leaving the DNA to be repaired
      subsequently. Defects in a TLS polymerase, Pol eta, lead to a form of Xeroderma
      pigmentosum, a disease characterized by severe skin sensitivity to sunlight
      damage and an increased incidence of skin cancer. Structurally, however,
      information on how ub-PCNA orchestrates the switching of these two classes of
      polymerases is lacking. We have solved the structure of ub-PCNA and demonstrate
      that the ubiquitin molecules in ub-PCNA are radially extended away from the PCNA
      without structural contact aside from the isopeptide bond linkage. This unique
      orientation provides an open platform for the recruitment of TLS polymerases
      through ubiquitin-interacting domains. However, the ubiquitin moieties, to the
      side of the equatorial PCNA plane, can place spatial constraints on the
      conformational flexibility of proteins bound to ub-PCNA. We show that ub-PCNA is
      impaired in its ability to support the coordinated actions of Fen1 and Pol delta
      in assays mimicking Okazaki fragment processing. This provides evidence for the
      novel concept that ub-PCNA may modulate additional DNA transactions other than
      TLS polymerase recruitment and switching.

PMID- 22592531
TI  - Sister chromatid cohesion establishment occurs in concert with lagging strand
      synthesis.
AB  - Cohesion establishment is central to sister chromatid tethering reactions and
      requires Ctf7/Eco1-dependent acetylation of the cohesin subunit Smc3. Ctf7/Eco1
      is essential during S phase, and a number of replication proteins (RFC complexes,
      PCNA and the DNA helicase Chl1) all play individual roles in sister chromatid
      cohesion. While the mechanism of cohesion establishment is largely unknown, a
      popular model is that Ctf7/Eco1 acetylates cohesins encountered by and located in
      front of the fork. In turn, acetylation is posited both to allow fork passage
      past cohesin barriers and convert cohesins to a state competent to capture
      subsequent production of sister chromatids. Here, we report evidence that
      challenges this pre-replicative cohesion establishment model. Our genetic and
      biochemical studies link Ctf7/Eco1 to the Okazaki fragment flap endonuclease,
      Fen1. We further report genetic and biochemical interactions between Fen1 and the
      cohesion-associated DNA helicase, Chl1. These results raise a new model wherein
      cohesin deposition and establishment occur in concert with lagging strand
      processing events and in the presence of both sister chromatids.

PMID- 22592532
TI  - Calcium/calmodulin-dependent protein kinase II (CaMKII) phosphorylates Raf-1 at
      serine 338 and mediates Ras-stimulated Raf-1 activation.
AB  - The calcium/calmodulin-dependent kinase II (CaMKII) participates with Ras to Raf
      1 activation, and it is necessary for activation of the extracellular signal
      regulated kinase (ERK) by different factors in epithelial and mesenchimal cells.
      Raf-1 activation is a complex multistep process, and its maximal activation is
      achieved by phosphorylation at Y341 by Src and at S338 by other kinase/s.
      Although early data proposed the involvement of p21-activated kinase 3 (Pak3),
      the kinase phosphorylating S338 remains to be definitively identified. In this
      study, we verified the hypothesis that CaMKII phosphorylates Raf-1 at Ser338. To
      do so, we determined the role of CaMKII in Raf-1 and ERK activation by oncogenic
      Ras and other factors. Serum, fibronectin, Src (Y527)  and Ras (V12)  activated
      CaMKII and ERK, at different extents. The inhibition of CaMKII attenuated Raf-1
      and ERK activation by all these factors. CaMKII was also necessary for the
      phosphorylation of Raf-1 at S338 by serum, fibronectin and Ras. Conversely,
      inhibition of Pak3 activation by blocking phosphatidylinositol 3-kinase was
      ineffective. The direct phosphorylation of S338 Raf-1 by CaMKII was demonstrated
      in vitro by interaction of purified kinases. These results demonstrate that Ras
      activates CaMKII, which, in turn, phosphorylates Raf-1 at S338 and participates
      in ERK activation upon different stimuli.

PMID- 22592533
TI  - Mucinous adenocarcinoma developed from human fallopian tube epithelial cells
      through defined genetic modifications.
AB  - Recent studies have suggested that some ovarian and pelvic serous carcinomas
      could originate from the fimbriated end of the distal fallopian tube. To test
      this hypothesis, we immortalized a normal human fallopian tube epithelial (FTE)
      cell line by using retrovirus-mediated overexpression of the early region of the
      SV40 T/t antigens and the human telomerase reverse transcriptase subunit (hTERT).
      These immortalized FTEs were then transformed by ectopic expression of oncogenic
      human HRAS (V12) . Tumorigenicity of the immortalized and/or transformed cells
      was subsequently tested by anchorage-independence growth assay and inoculation
      into nude mice via subcutaneous and intraperitoneal injection. As expected, the
      HRAS (V12) -transformed FTEs produced tumors through both subcutaneous and
      intraperitoneal injections, whereas no tumor growth was observed in immortalized
      FTEs. Unexpectedly, histopathological examination of tumors resulting from
      subcutaneous as well as intraperitoneal injections revealed largely poorly
      differentiated mucinous adenocarcinoma mixed with undifferentiated carcinoma. The
      tumor implants invaded extensively to the liver, colon, spleen, omentum, adrenal
      gland and renal capsule. Immunohistochemical staining of tumor cells showed
      positive staining for the epithelial cell markers cytokeratin AE1/AE3 and
      Mullerian lineage marker PAX8. Our study demonstrates that FTEs can generate
      poorly differentiated mucinous adenocarcinoma mixed with undifferentiated
      carcinoma through genetic modifications. Thus, we provide the first experimental
      evidence that fimbrial epithelial cells of the fallopian tube could be a
      potential source of ovarian mucinous adenocarcinoma.

PMID- 22592534
TI  - MiR-145 inhibits tumor angiogenesis and growth by N-RAS and VEGF.
AB  - MiR-145 is known as a tumor suppressor in numerous human cancers. However, its
      role in tumor angiogenesis remains poorly defined. In this study, we found that
      miR-145 was significantly downregulated in breast cancer tissues by using 106
      cases of normal and cancer tissues as well as in breast cancer cells. MiR-145
      exhibited inhibitory role in tumor angiogenesis, cell growth and invasion and
      tumor growth through the post-transcriptional regulation of the novel targets N
      RAS and VEGF-A. In addition, we provide evidence that the expression levels of
      miR-145 correlate inversely with malignancy stages of breast tumors, although
      there is no association between miR-145 levels and hormone receptor levels in
      breast cancer. Taken together, these results demonstrate that miR-145 plays
      important inhibitory role in breast cancer malignancy by targeting N-RAS and VEGF
      A, which may be potential therapeutic and diagnostic targets.

PMID- 22592535
TI  - Evaluation of the role of rats as reservoir hosts for fishborne zoonotic
      trematodes in two endemic northern Vietnam fish farms.
AB  - Fishborne zoonotic trematodes (FZTs) pose a food safety risk for the aquaculture
      industry in Vietnam. The risk of being infected from eating raw fish applies not
      only to humans but also to domestic animals which can serve as reservoir hosts in
      fish farms. The role of rodents, commonly found in fish farms, as reservoir hosts
      has not been adequately evaluated. To study this question, commensal and rice
      field rats were collected from fish farms in Nghia Lac and Nghia Phu communes,
      Nam Dinh province, Vietnam and examined for FZT infection. A total of 250 rats
      (Rattus norvegicus, Rattus argentiventer, and Bandicota indica) were collected
      and examined; the rats were trapped in the farm households (commensal) and in
      rice fields adjoining the fish ponds (field). The total prevalence of all
      parasites was 52.8 %: nematodes, 42.4 %; trematodes 18.0 %; and cestodes, (3.6
      %), including two zoonotic cestode species, Raillietina celebenisis and
      Hymenolepis diminuta. Although overall prevalence and intensity of parasite
      infection did not differ significantly among rat species or between the two
      communes, the intensity of nematode infection was significantly higher in
      commensal rats (p < 0.05). The only FZTs recovered were the intestinal flukes
      Echinostoma cinetorchis and Centrocestus formosanus, both at low prevalence.
      Because the most common FZTs found in fish from these communes are Haplorchis
      pumilio and Haplorchis taichui, neither of which were found in the rats, we
      conclude that rats are not significant reservoir hosts for FZT in these
      Vietnamese fish farms.

PMID- 22592536
TI  - Henneguya mauritaniensis n. sp. (Myxozoa) from the arterial bulb of Pagrus
      caeruleostictus (Valenciennes, 1830) off Mauritania.
AB  - We describe a new species of myxozoan, Henneguya mauritaniensis n. sp., extracted
      from the arterial bulb of the bluespotted seabream, Pagrus caeruleostictus
      (Valenciennes, 1830), collected in Mauritanian waters. Out of the 209 individuals
      examined, 30.1 % were infected with this new taxon. Spore total length ranged
      from 15.0 to 20.5 MUm with a mean of 17.9 MUm. The two polar capsules were equal
      in size, and pyriform and caudal appendages joined until mid-length. Morphometric
      analysis revealed significant differences between H. mauritaniensis n. sp. and
      morphologically similar species from this region as well as congeners known from
      other sparid hosts. Phylogenetic analysis of 18 S rDNA indicated that this new
      species is closely related to Henneguya pagri, reported recently from Pagrus
      major off Japan. Bayesian inference and maximum likelihood analyses of the 18 S
      rDNA dataset also revealed that species of marine Henneguya reported forming
      pseudocysts in the hearts of their fish hosts were closely related. Histological
      analysis of the H. mauritaniensis n. sp. pseudocysts embedded in the arterial
      bulb of P. caeruleostictus suggests that these parasites may cause considerable
      pathology, which may impact negatively on the health of the fish host. Finally,
      we discussed the importance of a combination of morphological and molecular
      analysis for species description because of high variability in size within the
      same taxa.

PMID- 22592537
TI  - Prevalence and treatment of 12-month DSM-IV disorders in the Northern Ireland
      study of health and stress.
AB  - PURPOSE: Prior to the current Northern Ireland Study of Health and Stress there
      have been no epidemiological studies which estimate the prevalence and treatment
      of mental health disorders across Northern Ireland based on validated diagnostic
      criteria. This paper provides the first nationally representative estimates of 12
      month DSM-IV anxiety, mood, impulse-control and substance disorders. Severity,
      demographic correlates, treatment and treatment adequacy of 12-month disorders
      are also examined. METHODS: Data were derived from a nationally representative
      face-to-face household survey of 4,340 participants (2,441 females and 1,899
      males) aged 18 years and older living in Northern Ireland using the World Health
      Organization Composite International Diagnostic Interview. Analyses were
      implemented using the SUDAAN software system. RESULTS: 12-month prevalence
      estimates were anxiety 14.6 %; mood 9.6 %; impulse control 3.4 %; substance 3.5
      %; any disorder 23.1 %. Of the 12-month cases, 28.8 % were classified as serious;
      33.4 % as moderate; and 37.8 % as mild. Females were more likely to have anxiety
      and mood disorders (p < 0.05) while males were more likely to have impulse
      control and substance disorders. Just 40 % of individuals with any 12-month DSM
      IV disorder received treatment in the previous 12 months. 78.6 % of those with a
      mental disorder who sought treatment received minimally adequate treatment.
      CONCLUSIONS: 12-month DSM-IV disorders are highly prevalent in Northern Ireland.
      A large proportion of those with mental health problems did not seek treatment.
      Further research is required to investigate the reasons behind low levels of
      treatment contact.

PMID- 22592538
TI  - Calibrated needle for ophthalmic fine needle aspiration biopsy.

PMID- 22592539
TI  - Solution NMR structure of Alr2454 from Nostoc sp. PCC 7120, the first structural
      representative of Pfam domain family PF11267.
AB  - Protein domain family PF11267 (DUF3067) is a family of proteins of unknown
      function found in both bacteria and eukaryotes. Here we present the solution NMR
      structure of the 102-residue Alr2454 protein from Nostoc sp. PCC 7120, which
      constitutes the first structural representative from this conserved protein
      domain family. The structure of Nostoc sp. Alr2454 adopts a novel protein fold.

PMID- 22592540
TI  - Evaluation of child health matters: a web-based tutorial to enhance school
      nurses' communications with families about weight-related health.
AB  - The goal of the current study was to assess the efficacy and acceptability of a
      web-based tutorial (Child Health Matters, CHM) designed to improve school nurses'
      communications with families about pediatric weight-related health issues. Using
      a randomized wait-list control design, a nationally representative sample of
      school nurses was assigned to immediate or delayed access conditions. Pre-, post
      , and follow-up assessments of knowledge, barriers to providing obesity
      treatment, and intended practices were conducted. Results indicated that,
      relative to wait-list controls, immediate-access nurses demonstrated significant
      increases in knowledge and decreases in perceived barriers to discussing weight
      related health, and significantly greater intentions to assess physical activity,
      and to recommend dietary changes and physical activity. Wait-list nurses
      demonstrated significant within-group improvements after completing CHM. Nurses
      reported a high degree of satisfaction with CHM. Results suggest that web-based
      tutorials can effect changes in nurses' knowledge, perceived barriers, and
      intended practices with regard to weight-related health care.

PMID- 22592541
TI  - The effect of wheel size on mobility performance in wheelchair athletes.
AB  - The purpose of the current study was to investigate the effects of different
      wheel sizes, with fixed gear ratios, on maximal effort mobility performance in
      wheelchair athletes. 13 highly trained wheelchair basketball players, grouped by
      classification level, performed a battery of 3 field tests in an adjustable
      wheelchair with 3 different wheel sizes (0.59 m, 0.61 m and 0.65 m). Performance
      was assessed using the time taken to perform drills, with velocity and
      acceleration data also collected via a wheelchair velocometer. 20 m sprint time
      improved in the 0.65 m condition (5.58 +/- 0.43 s, P=0.029) compared with 0.59 m
      (5.72 +/- 0.40 s). Acceleration performance over the first 2 (P=0.299) and 3
      (P=0.145) pushes was not statistically influenced by wheel size. However, the
      peak velocities reached were greater in the 0.65 m condition (4.77 +/- 0.46 m ?
      s(-1), P=0.078, Effect Size [ES]=0.63) compared with 0.59 m (4.61 +/- 0.40 m ? s(
      1)). Impact velocity, calculated as the change in velocity from the onset of a
      push to the following impact peak, to define coupling performance, was also
      significantly improved in 0.65 m wheels (0.14 +/- 0.14 m ? s(-1), P=0.006) than
      0.59 m wheels (0.05 +/- 0.10 m ? s(-1)). The time taken to complete the linear
      mobility (P=0.630) and the agility drill (P=0.505) were not affected by wheel
      size. Finally, no significant interactions existed between wheel size,
      classification and any performance measure. To conclude, larger 0.65 m wheels
      improved the maximal sprinting performance of highly trained wheelchair
      basketball players, without any negative effects on acceleration or
      manoeuvrability. Improvements in sprinting were attributed to a combination of
      the reduced drag forces experienced and improvements in coupling thought to be
      due to the lower angular velocities of the wheel/hand-rim when developing high
      wheelchair velocities in larger wheels.

PMID- 22592542
TI  - Listening to music in the first, but not the last 1.5 km of a 5-km running trial
      alters pacing strategy and improves performance.
AB  - We examined the effects of listening to music on attentional focus, rating of
      perceived exertion (RPE), pacing strategy and performance during a simulated 5-km
      running race. 15 participants performed 2 controlled trials to establish their
      best baseline time, followed by 2 counterbalanced experimental trials during
      which they listened to music during the first (M start) or the last (M finish)
      1.5 km. The mean running velocity during the first 1.5 km was significantly
      higher in M start than in the fastest control condition (p<0.05), but there was
      no difference in velocity between conditions during the last 1.5 km (p>0.05). The
      faster first 1.5 m in M start was accompanied by a reduction in associative
      thoughts compared with the fastest control condition. There were no significant
      differences in RPE between conditions (p>0.05). These results suggest that
      listening to music at the beginning of a trial may draw the attentional focus
      away from internal sensations of fatigue to thoughts about the external
      environment. However, along with the reduction in associative thoughts and the
      increase in running velocity while listening to music, the RPE increased linearly
      and similarly under all conditions, suggesting that the change in velocity
      throughout the race may be to maintain the same rate of RPE increase.

PMID- 22592543
TI  - Effects of overtraining on skeletal muscle growth and gene expression.
AB  - The aim of this study was to investigate the effects of overtraining on skeletal
      muscle growth and growth-related gene expression. The rats of overtraining group
      (OT) and overtraining recovery group (OTR) were subject to 11 experimental weeks
      of overtraining protocol. It was found that the absolute gastrocnemius muscle wet
      weight of the OT group was significantly lower than that of the sedentary group
      (23.6%, P<0.01). Serum creatine kinase was significantly higher in the OT and OTR
      groups than the sedentary group. CD68, CD163, MyoD, myogenin, IL-1beta, TNF
      alpha, IGF-I and MGF mRNA did not change in the OT group as compared with the
      sedentary group. IL-6 and TGF-beta1 mRNA in the OT group increased significantly
      as compared with the sedentary group (2.17 fold and 1.78 fold, respectively;
      P<0.01). IL-10 mRNA decreased significantly in the OT group (63%, P<0.01) and the
      OTR group (77%, P<0.01) compared to the sedentary group. COX-2 mRNA decreased
      significantly in the OT group (60%, P<0.01) and the OTR group (69%, P<0.01) from
      the sedentary group. uPA mRNA in the OT group was significantly lower than that
      in the sedentary group (32%, P<0.01). These data suggest that inflammatory
      cytokines, COX-2 and uPA may play roles in the inhibition of skeletal muscle
      growth induced by overtraining.

PMID- 22592544
TI  - Stroking parameters during continuous and intermittent exercise in regional-level
      competitive swimmers.
AB  - This study aimed to determine whether maximal lactate steady state (MLSS)
      represents a boundary above which not only physiological but also technical
      changes occur. On different days, 13 male swimmers (23 +/- 9 years) performed the
      following tests: 1) a 400-m all-out swim, to determine maximal aerobic speed (S
      400); 2) a series of 30-min sub-maximal swims, to determine continuous MLSS
      (MLSSc), and; 3) a series of 12*150 s sub-maximal swims, to determine
      intermittent MLSS (MLSSi). Stroke rate (SR), distance per stroke cycle (DS) and
      stroke index (SI) were analyzed at and above (102.5%) MLSSc and MLSSi. MLSSi
      (1.17 +/- 0.09 m.s (- 1)) was significantly higher than MLSSc (1.13 +/- 0.08 m.s
      (- 1)) while blood lactate concentration (mmol.L (- 1)) was similar between the 2
      conditions (4.3 +/- 1.1 and 4.4 +/- 1.5, respectively). The increase in SR and
      decreases in DS and SI were significant during MLSSi, 102.5% MLSSc and 102.5%
      MLSSi. During MLSSc, DS also decreased significantly (- 3.6%) but with no change
      in SR or SI. Thus, stroking technique of regional-level competitive swimmers
      changes over time when they swim at or above MLSS. This is the case during both
      continuous and intermittent swimming, despite steady state blood lactate
      concentrations.

PMID- 22592545
TI  - Impaired endothelial function and blood flow in repetitive strain injury.
AB  - Repetitive Strain Injury (RSI) is a disabling upper extremity overuse injury that
      may be associated with pathophysiological changes in the vasculature. In this
      study we investigated whether RSI is associated with endothelial dysfunction and
      impaired exercise-induced blood flow in the affected forearm. 10 patients with
      RSI (age, 40.2 +/- 10.3; BMI, 23.8 +/- 3.3) and 10 gender- and age-matched
      control subjects (age, 38.0 +/- 12.4; BMI, 22.7 +/- 3.4) participated in this
      study. Brachial artery blood flow was measured at rest and during 3-min periods
      of isometric handgrip exercise at 15%, 30% and 45% of the individual maximal
      voluntary contraction. Brachial artery endothelial function was assessed as the
      flow mediated dilation (FMD), by measuring brachial artery diameter and velocity
      before and after 5-min ischemic occlusion. We found a lower exercise-induced
      brachial artery blood flow in patients with RSI than in controls (p=0.04).
      Brachial artery FMD was significantly lower in patients with RSI than in controls
      (p<0.01), whilst a lower FMD was also found in patient with unilateral RSI when
      comparing the affected arm with the non-affected arm (p=0.04). Our results
      suggest that patients with RSI have an attenuated exercise-induced blood flow and
      an impaired endothelial function in the affected arm. These findings importantly
      improve our understanding of the pathophysiological mechanism of RSI.

PMID- 22592546
TI  - VO2 kinetics during heavy and severe exercise in swimming.
AB  - The purpose of this study was to describe the VO2 kinetics above and below
      respiratory compensation point (RCP) during swimming. After determination of the
      gas-exchange threshold (GET), RCP and VO(2max), 9 well-trained swimmers (21.0 +/-
      7.1 year, VO(2max)=57.9 +/- 5.1 ml.kg (- 1).min (- 1)), completed a series of
      "square-wave" swimming transitions to a speed corresponding to 2.5% below (S -
      2.5%) and 2.5% above (S+2.5%) the speed observed at RCP for the determination of
      pulmonary VO2 kinetics. The trial below (~2.7%) and above RCP (~2%) was performed
      at 1.28 +/- 0.05 m.s (- 1) (76.5 +/- 6.3% VO(2max)) and 1.34 0.05 m.s (- 1) (91.3
      +/- 4.0% VO(2max)), respectively. The time constant of the primary component was
      not different between the trials below (17.8 +/- 5.9 s) and above RCP (16.5 +/-
      5.1 s). The amplitude of the VO(2)slow component was similar between the exercise
      intensities performed around RCP (S - 2.5%=329.2 +/- 152.6 ml.min (- 1) vs.
      S+2.5%=313.7 +/- 285.2 ml.min (- 1)), but VO(2max) was attained only during trial
      performed above RCP (S-2.5%=91.4 +/- 5.9% VO(2max) vs. S+2.5%=103.0 +/- 8.2%
      VO(2max)). Thus, similar to the critical power during cycling exercise, the RCP
      appears to represent a physiological boundary that dictates whether VO(2)
      kinetics is characteristic of heavy- or severe-intensity exercise during
      swimming.

PMID- 22592547
TI  - Capillary cortisol sampling during high-intensity exercise.
AB  - Venepuncture is the established "gold standard" for sampling cortisol, but it is
      expensive, highly invasive and impractical for many experimental and clinical
      settings. Salivary free cortisol is a non-invasive and practical alternative;
      however, when cortisol concentrations exceed 500 nmol . L there is a lack of
      agreement between salivary (free) and venous (bound) cortisol. No known research
      has assessed whether capillary cortisol accurately reflects venous blood cortisol
      across a range of concentrations. The objective of the current study was to
      determine the agreement between capillary and venous blood samples of total
      plasma cortisol across a range of concentrations. 11 healthy male subjects (26.1
      +/- 5.3 years) were recruited. Capillary and venous blood samples were collected
      pre and post (immediately post and post 5, 10, 15 and 20 min) a treadmill VO2max
      test. Regression analysis revealed a strong relationship (R2=0.96, y=1.0028x +
      1.2964 (P<0.05)) between capillary and venous cortisol concentrations. A Bland
      Altman plot showed all data was within the upper and lower bounds of the 95%
      confidence interval, and no systematic bias was evident. In conclusion, capillary
      sampling is a valid technique for measuring bound cortisol across a range of
      concentrations.

PMID- 22592548
TI  - Irreversible muscle damage in bodybuilding due to long-term intramuscular oil
      injection.
AB  - Intramuscular oil injections generating slowly degrading oil-based depots
      represent a controversial subject in bodybuilding and fitness. However they seem
      to be commonly reported in a large number of non-medical reports, movies and
      application protocols for 'site-injections'. Surprisingly the impact of long-term
      (ab)use on the musculature as well as potential side-effects compromising health
      and sports ability are lacking in the medical literature. We present the case of
      a 40 year old male semi-professional bodybuilder with systemic infection and
      painful reddened swellings of the right upper arm forcing him to discontinue
      weightlifting. Over the last 8 years he daily self-injected sterilized sesame
      seed oil at numerous intramuscular locations for the purpose of massive muscle
      building. Whole body MRI showed more than 100 intramuscular rather than
      subcutaneous oil cysts and loss of normal muscle anatomy. 2-step septic surgery
      of the right upper arm revealed pus-filled cystic scar tissue with the near
      complete absence of normal muscle. MRI 1 year later revealed the absence of
      relevant muscle regeneration. Persistent pain and inability to perform normal
      weight training were evident for at least 3 years post-surgery. This alarming
      finding indicating irreversible muscle mutilation may hopefully discourage people
      interested in bodybuilding and fitness from oil-injections. The impact of such
      chronic tissue stress on other diseases like malignancy remains to be determined.

PMID- 22592549
TI  - Recovery of rotators strength after Latarjet surgery.
AB  - The purposes of this study were to prospectively determine changes in rotator
      cuff strength before and after surgical shoulder stabilization by Bristow
      Latarjet procedure and to better estimate time needed for rotator cuff strength
      recovery. 20 patients with recurrent anterior posttraumatic shoulder dislocation
      underwent internal (IR) and external (ER) rotator isokinetic evaluation before
      and 3, 6 and 21 months after Bristow-Latarjet surgery. In a seated position with
      45 degrees  of shoulder abduction in the scapular plane, both shoulders were
      evaluated concentrically with a Con-Trex(r) isokinetic dynamometer at 180 degrees
      ?s (- 1), 120 degrees ?s (- 1) and 60 degrees ?s (- 1). 3 months post-surgery, IR
      and ER strength of the operated shoulder were significantly lower than before
      surgery (- 28 +/- 20% for IR, - 17 +/- 17% for ER) (P<0.05). At 6 and 21 months
      post-surgery, IR and ER strength were comparable to strength before surgery;
      strength recovery is seen at 6 months post-surgery with long-term maintenance at
      21 months. Given the weakness 3 months post-surgery, return to sports (including
      overhead and contact sports) should be discussed, and 6 months post-surgery may
      be a better point for an athlete to resume practicing sports. Isokinetic rotator
      cuff strength evaluation appears to be relevant in helping to determine the need
      of continuing strength rehabilitation. Pre-surgical evaluation contributes to the
      relevance of later comparisons.

PMID- 22592550
TI  - Heterologous expression of the C-terminal antigenic domain of the malaria vaccine
      candidate Pfs48/45 in the green algae Chlamydomonas reinhardtii.
AB  - Malaria is a widespread and infectious disease that is a leading cause of death
      in many parts of the world. Eradication of malaria has been a major world health
      goal for decades, but one that still remains elusive. Other diseases have been
      eradicated using vaccination, but traditional vaccination methods have thus far
      been unsuccessful for malaria. Infection by Plasmodium species, the causative
      agent of malaria, is currently treated with drug-based therapies, but an increase
      in drug resistance has led to the need for new methods of treatment. A promising
      strategy for malaria treatment is to combine transmission blocking vaccines
      (TBVs) that prevent spread of disease with drug-based therapies to treat infected
      individuals. TBVs can be developed against surface protein antigens that are
      expressed during parasite reproduction in the mosquito. When the mosquito ingests
      blood from a vaccinated individual harboring the Plasmodium parasite, the
      antibodies generated by vaccination prevent completion of the parasites life
      cycle. Animal studies have shown that immunization with Pfs48/45 results in the
      production of malaria transmission blocking antibodies; however, the development
      of this vaccine candidate has been hindered by poor expression in both
      prokaryotic and eukaryotic hosts. Recently, the chloroplast of Chlamydomonas
      reinhardtii has been used to express complex recombinant proteins. In this study,
      we show that the C-terminal antigenic region of the Pfs48/45 antigen can be
      expressed in the chloroplast of the green algae C. reinhardtii and that this
      recombinant protein has a conformation recognized by known transmission blocking
      antibodies. Production of this protein in algae has the potential to scale to the
      very large volumes required to meet the needs of millions at risk for contracting
      malaria.

PMID- 22592551
TI  - Efficient (R)-3-hydroxybutyrate production using acetyl CoA-regenerating pathway
      catalyzed by coenzyme A transferase.
AB  - (R)-3-hydroxybutyrate [(R)-3HB] is a useful precursor in the synthesis of value
      added chiral compounds such as antibiotics and vitamins. Typically, (R)-3HB has
      been microbially produced from sugars via modified (R)-3HB-polymer-synthesizing
      pathways in which acetyl CoA is converted into (R)-3-hydroxybutyryl-coenzyme A
      [(R)-3HB-CoA] by beta-ketothiolase (PhaA) and acetoacetyl CoA reductase (PhaB).
      (R)-3HB-CoA is hydrolyzed into (R)-3HB by modifying enzymes or undergoes
      degradation of the polymerized product. In the present study, we constructed a
      new (R)-3HB-generating pathway from glucose by using propionyl CoA transferase
      (PCT). This pathway was designed to excrete (R)-3HB by means of a PCT-catalyzed
      reaction coupled with regeneration of acetyl CoA, the starting substance for
      synthesizing (R)-3HB-CoA. Considering the equilibrium reaction of PCT, the PCT
      catalyzed (R)-3HB production would be expected to be facilitated by the addition
      of acetate since it acts as an acceptor of CoA. As expected, the engineered
      Escherichia coli harboring the phaAB and pct genes produced 1.0 g L(-1) (R)-3HB
      from glucose, and with the addition of acetate into the medium, the concentration
      was increased up to 5.2 g L(-1), with a productivity of 0.22 g L(-1) h(-1). The
      effectiveness of the extracellularly added acetate was evaluated by monitoring
      the conversion of (13)C carbonyl carbon-labeled acetate into (R)-3HB using gas
      chromatography/mass spectrometry. The enantiopurity of (R)-3HB was determined to
      be 99.2% using chiral liquid chromatography. These results demonstrate that the
      PCT pathway achieved a rapid co-conversion of glucose and acetate into (R)-3HB.

PMID- 22592552
TI  - Identification of antibody-interacting proteins that contribute to the production
      of recombinant antibody in mammalian cells.
AB  - Protein folding and assembly processes are essential for antibody secretion;
      however, the endogenous proteins involved in these processes remain largely
      unknown. Therefore, except for some well-known endoplasmic reticulum (ER)
      chaperones such as GRP78/Bip and protein disulfide isomerase, enhancement of
      recombinant antibody expression by co-expression of interacting proteins has been
      largely elusive. Here, in addition to known ER chaperones, we identified
      additional endogenous proteins that interact with recombinant antibody in
      mammalian cells by immunoprecipitation coupled with liquid chromatography-tandem
      mass spectrometry. Most of our identified proteins enhanced antibody production,
      and furthermore, some of their combinations resulted in greater enhancement. In
      particular, eukaryotic initiation factor 4A combined with other proteins had
      approximately fourfold higher effect on antibody production. Identified proteins
      that could improve antibody expression contain not only ER-resident proteins like
      GRP78/Bip but also non-ER-resident proteins. These results suggest that this
      method could be effective in the investigation of novel proteins that are
      involved in enhancing recombinant antibody production because immunoprecipitation
      coupled with mass spectroscopy could identify proteins which directly interact
      with the antibody.

PMID- 22592553
TI  - Characterization of triglyceride lipase genes of fission yeast
      Schizosaccharomyces pombe.
AB  - Triglycerides (TG) are major storage lipids for eukaryotic cells. In this study,
      we characterized three genes of fission yeast Schizosaccharomyces pombe,
      SPCC1450.16c, SPAC1786.01c, and SPAC1A6.05c, that show high homology to
      Saccharomyces cerevisiae TG lipase genes, TGL3, TGL4, and TGL5. Deletion of each
      gene increased TG content by approximately 1.7-fold compared to the parental wild
      type strain, and their triple deletion mutant further increased TG content to 2.7
      fold of the wild-type strain, suggesting that all three genes encode TG lipase
      and are functioning in S. pombe. The triple deletion mutant showed no growth
      defect in rich and synthetic medium, but its growth was sensitive to cerulenin,
      an inhibitor of fatty acid synthesis. This growth defect by cerulenin was
      restored by adding oleic acid in media, suggesting that these genes were involved
      in the mobilization of TG in S. pombe. When ricinoleic acid was produced in the
      triple mutant by introducing CpFAH12 fatty acid hydroxylase gene from Claviceps
      purpurea, percent composition of ricinoleic acid increased by 1.1-fold compared
      to the wild-type strain, in addition to a 1.6-fold increase in total fatty acid
      content per dry cell weight (DCW). In total, the ricinoleic acid production per
      DCW increased by 1.8-fold in the triple deletion mutant.

PMID- 22592554
TI  - Transcriptome profiling of Zymomonas mobilis under furfural stress.
AB  - Furfural from lignocellulosic hydrolysates is the prevalent inhibitor to
      microorganisms during cellulosic ethanol production, but the molecular mechanisms
      of tolerance to this inhibitor in Zymomonas mobilis are still unclear. In this
      study, genome-wide transcriptional responses to furfural were investigated in Z.
      mobilis using microarray analysis. We found that 433 genes were differentially
      expressed in response to furfural. Furfural up- or down-regulated genes related
      to cell wall/membrane biogenesis, metabolism, and transcription. However,
      furfural has a subtle negative effect on Entner-Doudoroff pathway mRNAs. Our
      results revealed that furfural had effects on multiple aspects of cellular
      metabolism at the transcriptional level and that membrane might play important
      roles in response to furfural. This research has provided insights into the
      molecular response to furfural in Z. mobilis, and it will be helpful to construct
      more furfural-resistant strains for cellulosic ethanol production.

PMID- 22592555
TI  - PTSA-catalyzed Mannich-type-cyclization-oxidation tandem reactions: one-pot
      synthesis of 1,3,5-substituted pyrazoles from aldehydes, hydrazines and alkynes.
AB  - A convenient one-pot Mannich-type-cyclization-oxidation tandem process has been
      developed for the synthesis of 1,3,5-trisubstituted pyrazoles derivatives from
      aldehydes, hydrazines and alkynes using p-toluenesulfonic acid monohydrate (PTSA)
      as a multifunctional catalyst. This method provides a flexible and rapid route to
      1,3,5-trisubstituted pyrazoles.

PMID- 22592556
TI  - Effects and possible mechanisms of acupuncture at ST36 on upper and lower
      abdominal symptoms induced by rectal distension in healthy volunteers.
AB  - Background acupuncture (AP) has been shown to have a therapeutic potential for
      gastrointestinal motility disorders. The aims of this study were to investigate
      the effects and possible mechanisms of acupuncture on postprandial upper and
      lower abdominal symptoms induced by rectal distension (RD). Twenty healthy
      volunteers were involved in a two-session study (AP and sham-AP, AP and no-AP, or
      sham-AP and no-AP). In 12 of the volunteers, RD was performed for 60 min in the
      postprandial state, and AP at ST36 or sham-AP was performed during the second 30
      min period of RD. Gastric slow waves and heart rate variability (HRV) were
      recorded using the electrogastrogram and electrocardiogram, respectively. Upper
      and lower abdominal symptoms were scored during RD with AP and sham-AP. In five
      of the subjects, an additional experiment with two sessions (with AP and no-AP)
      was performed. In the remaining eight volunteers, the same experiment was
      performed with sham-AP and no-AP was performed. The results were, first, RD at an
      average volume of 171 ml induced upper and lower abdominal symptoms (P < 0.01).
      AP, but not sham-AP or no-AP, reduced both upper and lower abdominal symptoms (P
      < 0.05). Second, RD decreased the percentage of normal gastric slow waves (P <
      0.05). AP improved gastric slow waves compared with sham-AP or no-AP (P < 0.05).
      Third, in the larger, but not smaller, sample size experiment, the vagal activity
      during the RD plus AP period was significantly higher than that during the RD
      alone period in the same session and the corresponding period with sham-AP or no
      AP in other sessions (P < 0.05). Neither sham-AP nor no-AP showed any effects on
      vagal activity (P > 0.05). Finally, in the experiment with eight volunteers,
      neither sham-AP nor no-AP showed any effects on RD-induced impairment in gastric
      slow waves, abdominal symptoms, or vagal activity (P > 0.05). The conclusions are
      RD induces upper or lower abdominal symptoms and impairs gastric slow waves in
      healthy volunteers. AP at ST36 is able to improve upper and lower abdominal
      symptoms and impaired gastric slow waves induced by RD, possibly mediated via the
      vagal pathway.

PMID- 22592557
TI  - Tryptophan metabolism activation by indoleamine 2,3-dioxygenase in adipose tissue
      of obese women: an attempt to maintain immune homeostasis and vascular tone.
AB  - Human obesity is characterized by chronic low-grade inflammation in white adipose
      tissue and is often associated with hypertension. The potential induction of
      indoleamine 2,3-dioxygenase-1 (IDO1), the rate-limiting enzyme in
      tryptophan/kynurenine degradation pathway, by proinflammatory cytokines, could be
      associated with these disorders but has remained unexplored in obesity. Using
      immunohistochemistry, we detected IDO1 expression in white adipose tissue of
      obese patients, and we focused on its contribution in the regulation of vascular
      tone and on its immunoregulatory effects. Concentrations of tryptophan and
      kynurenine were measured in sera of 36 obese and 15 lean women. The expression of
      IDO1 in corresponding omental and subcutaneous adipose tissues and liver was
      evaluated. Proinflammatory markers and T-cell subsets were analyzed in adipose
      tissue via the expression of CD14, IL-18, CD68, TNFalpha, CD3epsilon, FOXP3 [a
      regulatory T-cell (Treg) marker] and RORC (a Th17 marker). In obese subjects, the
      ratio of kynurenine to tryptophan, which reflects IDO1 activation, is higher than
      in lean subjects. Furthermore, IDO1 expression in both adipose tissues and liver
      is increased and is inversely correlated with arterial blood pressure.
      Inflammation is associated with a T-cell infiltration in obese adipose tissue,
      with predominance of Th17 in the omental compartment and of Treg in the
      subcutaneous depot. The Th17/Treg balance is decreased in subcutaneous fat and
      correlates with IDO1 activation. In contrast, in the omental compartment, despite
      IDO1 activation, the Th17/Treg balance control is impaired. Taken together, our
      results suggest that IDO1 activation represents a local compensatory mechanism to
      limit obesity-induced inflammation and hypertension.

PMID- 22592558
TI  - Effect of cold acclimation on troponin I isoform expression in striated muscle of
      rainbow trout.
AB  - In vertebrates each of the three striated muscle types (fast skeletal, slow
      skeletal, and cardiac) contain distinct isoforms of a number of different
      contractile proteins including troponin I (TnI). The functional characteristics
      of these proteins have a significant influence on muscle function and
      contractility. The purpose of this study was to characterize which TnI gene and
      protein isoforms are expressed in the different muscle types of rainbow trout
      (Oncorhynchus mykiss) and to determine whether isoform expression changes in
      response to cold acclimation (4 degrees C). Semiquantitative real-time PCR was
      used to characterize the expression of seven different TnI genes. The sequence of
      these genes, cloned from Atlantic salmon (Salmo salar) and rainbow trout, were
      obtained from the National Center for Biotechnology Information databases. One
      dimensional gel electrophoresis and tandem mass spectrometry were used to
      identify the TnI protein isoforms expressed in each muscle type. Interestingly,
      the results indicate that each muscle type expresses the gene transcripts of up
      to seven TnI isoforms. There are significant differences, however, in the
      expression pattern of these genes between muscle types. In addition, cold
      acclimation was found to increase the expression of specific gene transcripts in
      each muscle type. The proteomics analysis demonstrates that fast skeletal and
      cardiac muscle contain three TnI isoforms, whereas slow skeletal muscle contains
      four. No other vertebrate muscle to date has been found to express as many TnI
      protein isoforms. Overall this study underscores the complex molecular
      composition of teleost striated muscle and suggests there is an adaptive value to
      the unique TnI profiles of each muscle type.

PMID- 22592560
TI  - Simplifying the synthesis of dendrimers: accelerated approaches.
AB  - Dendrimers are highly branched and monodisperse macromolecules that display an
      exact and large number of functional groups distributed with unprecedented
      control on the dendritic framework. Based on their globular structure, compared
      to linear polymers of the same molecular weight, dendrimers are foreseen to
      deliver extraordinary features for applications in areas such as cancer therapy,
      biosensors for diagnostics and light harvesting scaffolds. Of the large number of
      reports on dendrimer synthesis only a few have reached commercial availability.
      This limitation can be traced back to challenges in the synthetic paths including
      a large number of reaction steps required to obtain dendritic structures with
      desired features. Along with an increased number of reaction steps come not only
      increased waste of chemical and valuable starting materials but also an increased
      probability to introduce structural defects in the dendritic framework. This
      tutorial review briefly covers traditional growth approaches to dendrimers and
      mainly highlights accelerated approaches to dendrimers. A special focus
      capitalizes on the impact of the click chemistry concept on dendrimer synthesis
      and the promise it has to successfully accomplish highly sophisticated
      dendrimers, both traditional as well as heterofunctional, in a minimum number of
      chemical steps. It is clear that accelerated synthetic approaches are of greatest
      importance as these will encourage the scientific community to synthesize and
      access dendrimers for specific applications. The final goal of accelerated
      synthesis is to deliver economically justified dendritic materials for future
      applications without compromising the environmental perspective.

PMID- 22592559
TI  - Multiple exposures to unloading decrease bone's responsivity but compound
      skeletal losses in C57BL/6 mice.
AB  - A single exposure to mechanical unloading can result in significant bone loss,
      but the consequences of multiple exposures are largely unknown. Within a 18-wk
      period, adult C57BL/6 male mice were exposed to 2 wk of hindlimb unloading (HLU)
      followed by 4 wk of reambulation (RA) once (1x-HLU), twice (2x-HLU), or three
      times (3x-HLU), or served as ambulatory age-matched controls. In vivo MUCT
      longitudinally tracked changes in trabecular and cortical compartments of the
      femur. Normally ambulating control mice experienced significant age-related loss
      in trabecular bone volume fraction throughout the course of the experiment. This
      loss was compounded by HLU with 2x- and 3x-HLU mice experiencing a 27% and 24%
      greater reduction in trabecular bone and a 60% and 63% inhibition of age-related
      trabecular thickening. The recovery of cortical bone was also incomplete during
      each 4-wk RA period and, at completion of the experiment, cortical area in 3x-HLU
      mice was 5% smaller than in control and 1x-HLU. When eliminating age as a
      confounding variable, comparison between individual HLU/RA cycles showed that the
      magnitude of the response diminished during subsequent exposures. The extent of
      trabecular thinning in mice unloaded for the first time was 1.6-fold greater than
      the second time and nearly twofold greater than the third time. Similarly, the
      increase in trabecular thickness during the first RA cycle was twofold greater
      than during the second and third RA cycle. Together, our data demonstrate that
      even though multiple exposures to mechanical unloading are more detrimental than
      a single unloading period, bone's mechanosensitivity is reduced with consecutive
      unloading/reambulation cycles.

PMID- 22592562
TI  - Obstruction of distal left anterior descending artery by the right ventricular
      lead of an implantable cardiac defibrillator.

PMID- 22592563
TI  - Molecular integrity and global gene expression of breast and lung cancer stem
      cells under long-term storage and recovery.
AB  - Cryopreservation is a common procedure widely used in biological and clinical
      sciences. Similar protocols are also applied in preserving cancer stem cells, a
      field with high promises and challenges. Specific cell surface membrane proteins
      are considered to be biomarkers of cancer stem cells and they may play a critical
      role in differentiating stem cells from non stem cells. We have looked at the
      possible effect of long-term cryopreservation on the molecular integrity of
      breast MCF7 and lung, A549 and H460, cancer stem cells and to assess if these
      cells are more sensitive to long-term storage process. We analyzed the expression
      of CD24 and CD38 as two potent biomarkers of lung cancer stem cells and EpCAM and
      ALDH that are used as biomarkers of a wide range of cancer stem cells. We also
      selected three genes essential for the normal functioning of the cells, Fos,
      MUC1, and HLA. Our results indicate a pattern of down-regulation in the
      expression of the genes following freezing, in particular among cell surface
      marker proteins. Global gene expression of the post-thaw breast and lung cancer
      stem cells also reveals a significant down-regulation in freeze-thaw cells
      independent from each other. Analyzing the canonical pathways between two
      populations reveals a significant alteration in the gene expression of the
      pathways involved in cell cycle, mitosis, and ataxia telangiectasia mutated
      pathways. Overall, our results indicate that current protocols for long-term
      storage of lung and breast cancer stem cells may substantially influence the
      activity and function of genes.

PMID- 22592564
TI  - TTR-related amyloid neuropathy: clinical, electrophysiological and pathological
      findings in 15 unrelated patients.
AB  - Familial amyloid polyneuropathy (FAP) is a rare condition caused by mutations of
      the transthyretin (TTR) gene and it is generally characterized by a length
      dependent polyneuropathy affecting prevalently the small fibers. We reviewed
      clinical, electrophysiological and pathological findings of 15 unrelated patients
      with genetically confirmed TTR-FAP. All patients presented a progressive sensory
      motor polyneuropathy. Pathological findings were negative for amyloid deposits in
      about half of the cases. Sequence analysis of TTR gene revealed the presence of
      three different mutations (p.Val30Met, p.Phe64Leu, and p.Ala120Ser). The
      p.Val30Met was the most frequently identified mutation and it often occurred in
      apparently sporadic cases. Conversely, the p.Phe64Leu generally presented in a
      high percentage of familial cases in patients coming from Southern Italy.
      Clinicians should consider, to avoid misdiagnosis, the screening for TTR
      mutations in patients presenting with progressive axonal polyneuropathy of
      undetermined etiology, including apparently sporadic cases with pathological
      examinations negative for amyloid deposition. 

PMID- 22592565
TI  - Granny trips down: is she carrying the big bad wolf?

PMID- 22592566
TI  - Pulmonary infections imitating lung cancer: clinical presentation and
      therapeutical approach.
AB  - BACKGROUND: Pulmonary infections occasionally present with infectious
      pseudotumour of the lung not easily distinguishable from true pulmonary neoplasm.
      In such cases, radiographic findings and clinical manifestation are highly
      suggestive of lung cancer. These inflammatory lung lesions cause significant
      diagnostic problems and appropriate therapy is often considerably delayed. We
      therefore report on our experience with infectious pseudotumour of the lung
      caused by bacterial, mycobacterial and fungal pulmonary infections. METHODS: In a
      retrospective case series, patients with lung infections simulating pulmonary
      carcinoma were identified. Clinical presentation, radiological features, surgical
      procedures and outcome were analysed. RESULTS: There were seven male and six
      female patients with a mean age of 53 years. Presumed pulmonary carcinoma and
      hemoptysis were main reasons for hospital admission. Procedures performed were
      video-assisted thoracoscopic wedge resection (6), lobectomy (5), video-assisted
      thoracoscopic lobectomy and open wedge resection each in one case. Pathologic
      examination of the obtained specimens revealed tuberculoma (5), aspergilloma (3),
      pulmonary actinomycosis related pseudotumour (3) and coccidioidoma (2). Following
      definite diagnosis, patients with tuberculosis and fungal infections received
      antituberculotic and antifungal medications, respectively. Patients suffering
      from pulmonary actinomycosis received penicillin. There was no in-hospital
      mortality. One re-thoracotomy was mandatory because of pleural empyema.
      CONCLUSIONS: Pulmonary infections simulating lung cancer require surgical removal
      both for establishing definite diagnosis and to manage complications like
      haemoptysis and ongoing contamination of the airways by infectious agents.
      Whenever feasible, limited thoracoscopic resections are preferable. Following
      definite diagnosis antimicrobial drug therapy for a sufficient length of time is
      mandatory.

PMID- 22592567
TI  - Triterpenoids.
AB  - This review covers the isolation and structure determination of triterpenoids,
      including squalene derivatives, protostanes, lanostanes, holostanes,
      cycloartanes, dammaranes, euphanes, tirucallanes, tetranortriterpenoids,
      quassinoids, lupanes, oleananes, friedelanes, ursanes, hopanes, serratanes and
      saponins; 305 references are cited.

PMID- 22592570
TI  - How can 5-HT(3) receptor antagonists exert analgesic properties?

PMID- 22592569
TI  - Antioxidant treatment prevents cognitive impairment and oxidative damage in
      pneumococcal meningitis survivor rats.
AB  - Pneumococcal meningitis is associated with the highest fatality case ratios in
      the world. Most of patients that survive present neurologic sequelae at later
      times as well as biochemicals alterations such as oxidative stress in both
      earlier and later times after central nervous system infection. In this context,
      we evaluated the effect of antioxidant treatment on memory and oxidative
      parameters in the hippocampus of meningitis survivor rats 10 days after
      infection. To this aim, the animals underwent a magna cistern tap receiving
      either 10 MUL sterile saline as a placebo or an equivalent volume of a
      Streptococcus pneumoniae suspension at the concentration 5x10(9) cfu/mL. The
      animals submitted to meningitis were divided into the following groups: 1)
      treated with antibiotic, 2) treated with basic support plus N-acetylcysteine, 3)
      treated with basic support plus deferoxamine, 4) treated with basic support plus
      N-acetylcysteine and deferoxamine, or 5) treated with N-acetylcysteine plus
      deferoxamine. Ten days after meningitis, the animals underwent inhibitory
      avoidance and habituation to an open field tasks and, immediately after, were
      assessed for oxidative damage in the hippocampus and cortex. The meningitis group
      showed significantly decreased performance in latency retention compared with the
      sham group in the inhibitory avoidance task. In the open-field task, the
      meningitis group presented memory impairment after meningitis. All these memory
      impairments were prevented by N-acetylcysteine plus deferoxamine with or without
      basic support and its isolate use. In addition, there was an increase of lipid
      phosphorylation in cortex and hippocampus and all the combined antioxidants
      attenuated lipid phosphorylation in both structures. On the other hand, there was
      an increase of protein phosphorylation in cortex and N-acetylcysteine plus
      deferoxamine with or without basic support prevented it. Thus, we hypothesize
      that oxidative stress may be related to cognitive impairment in pneumococcal
      meningitis.

PMID- 22592571
TI  - The effects of cyclosporin-A on functional outcome and axonal regrowth following
      spinal cord injury in adult rats.
AB  - It has been shown that the immunophilin ligands have the special advantage in
      spinal cord repair. In this study, the effects of cyclosporine A (CsA) on
      functional recovery and histological outcome were evaluated following spinal cord
      injury in rats. After spinal cord hemisection in thirty six adult female Sprague
      Dawley rats (200- 250 g), treatment groups received CsA (2.5 mg/kg i.p.) at 15min
      and 24h after lesion (CsA 15min group and CsA 24h group) daily, for 8 weeks.
      Control and sham groups received normal saline and in sham operated animals the
      spinal cord was exposed in the same manner as treatment groups, but was not
      hemisected. Hindlimb motor function was assessed in 1, 3, 5 and 7 weeks after
      lesion, using locomotive rating scale developed by Basso, Bresnahan and Beattie
      (BBB). Motor neurons were counted within the lamina IX of ventral horn and lesion
      size was measured in 5 mm of spinal lumbar segment with the epicenter of the
      lesion site. The mean number of motor neurons and the mean BBB scale in 3, 5 and
      7 weeks in CsA 15min groups significantly increased compared to the control
      group. Although, the lesion size reduced in rats with CsA treatment compared to
      the control group, no significant difference was observed. Thus, it can be
      concluded that CsA can improve locomotor function and histological outcome in the
      partial spinal cord injury.

PMID- 22592568
TI  - Engineering biomaterials to integrate and heal: the biocompatibility paradigm
      shifts.
AB  - This article focuses on one of the major failure routes of implanted medical
      devices, the foreign body reaction (FBR)--that is, the phagocytic attack and
      encapsulation by the body of the so-called "biocompatible" biomaterials
      comprising the devices. We then review strategies currently under development
      that might lead to biomaterial constructs that will harmoniously heal and
      integrate into the body. We discuss in detail emerging strategies to inhibit the
      FBR by engineering biomaterials that elicit more biologically pertinent
      responses.

PMID- 22592572
TI  - Effect of vitamin C administration on leukocyte vitamin C level and severity of
      bronchial asthma.
AB  - Oxidative stress mediated by reactive oxygen species is known to contribute to
      the inflammatory process of bronchial asthma. Reactive oxygen species are
      released into the bronchial tree by activated inflammatory cells. In this study,
      we aimed to determine the effect of vitamin C administration on leukocyte vitamin
      C level as well as severity of asthma. In this double blind clinical trial study
      we evaluated 60 patients with chronic stable asthma. The patients were divided
      into two groups (A and B) including 30 patients in each group. Patients in these
      groups were matched according to their age, weight, height, gender, BMI and drug
      consumption. In addition to standard asthma treatment (according to stepwise
      therapy in 4th step of bronchial asthma) in which the patients were controlled
      appropriately, group A received 1000 mg vitamin C daily and group B received
      placebo. At the baseline and after one month treatment, non-fasting blood samples
      were drawn for laboratory evaluations. Asthmatic patient's clinical condition was
      evaluated through standard pulmonary function test (PFT). The mean (+/-SD)
      leukocyte vitamin C level in group A at the baseline and after one month
      treatment with 1000 mg/day vitamin C, were 0.0903 (+/-0.0787) ug/108 leukocytes
      and 0.1400 (+/-0.0953) ug/108 leukocytes respectively (P<0.05). The mean (+/-SD)
      leukocyte vitamin C level in group B at the baseline and after one month
      administration of placebo, were 0.0867 (+/-0.0629) ug/108 leukocytes and
      0.0805(+/-0.0736) ug/108 leukocytes respectively. The leukocyte vitamin C level
      in group A was higher than those of group B after one month treatment with
      vitamin C and placebo and the difference was statistically significant (P<0.05).
      Comparing PFT (FEV1, FVC and FEV1/FVC) in group B during the study period showed
      a significant increase in FEV1 (P<0.05), while the other two parameters remained
      unchanged. In group A, who received 1000 mg/day vitamin C, none of the spirometry
      parameters changed after one month treatment, indicating no effect of vitamin C
      treatment in the spirometry parameters.

PMID- 22592573
TI  - Ondansetron pretreatment reduces pain on injection of propofol.
AB  - To assess the effectiveness of ondansetron pretreatment in alleviating propofol
      injection pain, 135 patients were randomly assigned to one of following three
      groups. Group 1 who received up to 2 mL pretreatment 50 mg tramadol in the
      saline, group 2 cases who received up to 2 mL pretreatment 4 mg ondansetron in
      saline, and group 3 who received up to 2 mL solution saline. A 20 gauge cannula
      was placed into the largest vein on the dorsum of the hand. Tourniquet was closed
      to the arm above the cannula and inflates to 70 mmHg, and then drug was injected.
      After 20 seconds, the tourniquet deflated, and propofol 2mg/kg injected over 10
      seconds and pain assessment was made. RESULTS: Tramadol and ondansetron
      significantly reduced the incidence and severity of propofol injection pain more
      than placebo (P=0.001). The efficacy of ondansetron in alleviating the pain on
      injection of propofol was no different from tramadol (P=0.330). Ondansetron
      pretreatment may be used to reduce the incidence of pain on injection of
      propofol, an advantage added to the useful prevention of postoperative nausea and
      vomiting.

PMID- 22592574
TI  - Fatigue, depression and sleep disturbances in Iranian patients with multiple
      sclerosis.
AB  - Fatigue is one of the most frequent symptoms in patients with multiple sclerosis
      (MS) and it is difficult to clarify the nature of this symptom and manage it.
      This study was aimed to evaluate the frequency of fatigue, depression and sleep
      disturbances in Iranian patients with MS. 100 patients from the outpatient MS
      clinic of Sina hospital were asked to complete Beck Depression Inventory (BDI),
      Pittsburg Sleep Quality Index (PSQI), Sleep Disorder Questionnaire (SDQ),
      Modified Fatigue Impact Scale (MFIS) and Epworth Sleepiness Scale (ESS)
      questionnaires. Student's t-test, ANOVA, Spearman correlation and Stepwise
      multiple linear regressions by SPSS version 15.0 were used for data analysis.
      From participants, 64 had fatigue complaint during day time and 36 did not feel
      fatigued. BDI, PSQI, MFIS and SDQ scores were significantly higher in fatigued
      patients than non-fatigued group but there were no statistically significant
      differences in ESS, EDSS and duration of disease between fatigued and non
      fatigued cases. There were significant correlations between MFIS and BDI scores
      (r=0.49, P=0.01), MFIS and PSQI scores (r=0.399, P=0.01) and MFIS and ESS
      (r=0.25, P=0.01). This study demonstrates that depression is not the only cause
      of fatigue in patients with MS and it is also associated with sleep disorders, so
      this complaint should be carefully evaluated and managed in these patients.

PMID- 22592575
TI  - Radiology employees' quality of work life.
AB  - Quality of work Life (QWL) originates from interactions between employees' needs
      and relative organizational resources. QWL is aimed to improve and retain
      employees' satisfaction, productivity and effectiveness of all organizations. A
      cross-sectional descriptive study was conducted among 15 Tehran University of
      Medical Sciences. A Cross-Sectional, descriptive study was conducted among 15
      Tehran University of Medical Sciences' Hospitals' Radiology Departments'
      Employees by QWL questionnaire. Respondents were asked to express their attitudes
      about a range of key factors as the most important issues impacting their QWL.
      The data was collected and analyzed by SPSS version 15 software. Most of the
      respondents indicated that they were unsatisfied and very unsatisfied with key
      factors of their QWL. Comparison of QWL key factors of TUMS radiology employees
      with the other countries indicated that most of the employees are unsatisfied
      with their poor QWL factors. We hope, the implications of these findings
      deliberate to improve QWL within each of TUMS hospitals radiology departments and
      also be relevant and value to policymakers of healthcare organizations in Iran.

PMID- 22592576
TI  - Assessment of substances abuse in burn patients by using drug abuse screening
      test.
AB  - There has been an increase in the frequency of substance abuse among hospitalized
      burn injury patients. However, few studies have investigated substance abuse
      among burn patients. This study was aimed to identify the incidence of substance
      abuse in burn injury patients using the "Drug Abuse Screening Test" (DAST-20). We
      determined the validity of DAST-20 in spring 2010. Subsequently, this descriptive
      study was performed on 203 burn injury patients who fit the study's inclusion
      criteria. We chose a score of 6 as the cutoff and thus achieved a sensitivity of
      89% and a specificity of 85% for the DAST-20. During the study, we gathered
      demographic data, burn features and DAST-20 results for all patients. Patients
      with scores of 6 or more were considered to be substances abusers. A statistical
      analysis was conducted using SPSS v16 software. According to the DAST-20 results,
      33% of the patients were in the user group. The mean score of DAST-20 was
      significantly higher among users than it was among nonusers (P<0.05). The level
      of substance abuse was severe in 77% of users. No significant differences were
      found among the substances, with the exception of alcohol. Substance abuse is an
      important risk factor for burn patients. In addition, this study showed that DAST
      20 is a valid screening measure for studies on burn patients.

PMID- 22592577
TI  - The prevalence of hepatitis B virus surface antigen (HBsAg) variations and
      correlation with the clinical and serologic pictures in chronic carriers from
      Khorasan Province, North-East of Iran.
AB  - This study was designed to determine the correlation of hepatitis B virus surface
      Ag (HBsAg) variations with the clinical/serological pictures among chronic HBsAg
      positive patients. The surface gene (S-gene) was amplified and directly sequenced
      in twenty-five patients. Eight samples (group I) contained at least one mutation
      at the amino acid level. Five showed alanine aminotransferase (ALT) levels above
      the normal range of which only one sample was anti-HBe positive. Group II (17
      samples) did not contain any mutation, 4 were anti-HBe positive and 9 had
      increased ALT levels. In both groups, from a total of 18 mutations, 5 (27.5%) and
      13 (72.5%) occurred in anti-HBe and HBeAg positive groups respectively. The small
      number of amino acid mutations might belong to either the initial phase of
      chronicity in our patients; or that even in anti-HBe positive phase in Iranian
      genotype D-infected patients, a somehow tolerant pattern due to the host genetic
      factors may be responsible.

PMID- 22592578
TI  - Situation of medical sciences in 50 top countries from 1996 to 2010--based on
      quality and quantity of publications.
AB  - In research outputs both quality and quantity are of critical value and
      evaluation of both aspects is required for best evaluation. Several studies have
      worked on single or two-dimensional methods that provide the assessment of
      quality, quantity or both simultaneously in different branches of sciences, but
      none of them have played a role in a particular area of medicine. This study has
      been conducted to compare countries worldwide in the field of medical researches.
      Measuring both quality and quantity of researches is performed separately. In
      order to evaluate countries from both aspects of quantity and quality of research
      outputs, a modified form of the citation per publication (CPPm) and publication
      per population (PPPm) were used to make these indices comparable through
      different years and nations by normalizing the values according to the world
      average standards. When countries are ranked by CPPm, Iceland ranks the 1st with
      the score of 1.98, Faroe Islands and Gambia rank the 2nd and the 3rd with scores
      of 1.84 and 1.63, respectively. In PPPm Switzerland, Sweden and Denmark ranked
      the top three with scores of 13.34, 11.67 and 10.32, respectively. Iran ranked 71
      in CPPm and 141 in PPPm. Ranking countries makes it possible to identify
      countries which have performed better in research outcomes by means of quality
      and quantity; thus, reforming policies can be taken into action to lower the
      waste of money, higher quality and quantity of outputs while providing helpful
      tip(s) for institutions to improve.

PMID- 22592579
TI  - Effects of educational intervention on long-lasting insecticidal nets use in a
      malarious area, southeast Iran.
AB  - Long-lasting insecticidal nets (LLINs) have been advocated as an effective tool
      against malaria transmission. However, success of this community based
      intervention largely depends on the knowledge and practice regarding malaria and
      its prevention. According to the national strategy plan on evaluation of LLINs
      (Olyset nets), this study was conducted to determine the perceptions and
      practices about malaria and to improve use of LLINs in Bashagard district, one of
      the important foci of malaria in southeast Iran. The study area comprised 14
      villages that were randomized in two clusters and designated as LLINs and
      untreated nets. Each of households in both clusters received two bed nets by the
      free distribution and delivery. After one month quantitative data collection
      method was used to collect information regarding the objectives of the study. On
      the basis of this information, an educational program was carried out in both
      areas to increase motivation for use of bed nets. Community knowledge and
      practice regarding malaria and LLIN use assessed pre- and post-educational
      program. The data were analyzed using SPSS ver.16 software. At baseline, 77.5% of
      respondents in intervention and 69.4 % in control area mentioned mosquito bite as
      the cause of malaria, this awareness increased significantly in intervention
      (90.3%) and control areas (87.9%), following the educational program. A
      significant increase also was seen in the proportion of households who used LLINs
      the previous night (92.5%) compared with untreated nets (87.1%). Educational
      status was an important predictor of LLINs use. Regular use of LLIN was
      considerably higher than the targeted coverage (80%) which recommended by World
      Heaths Organization. About 81.1% and 85.3% of respondents from LLIN and control
      areas reported that mosquito nuisance and subsequent malaria transmission were
      the main determinants of bed net use. These findings highlight a need for
      educational intervention in implementation of long-lasting insecticidal nets;
      this should be considered in planning and decision-making in the national malaria
      control program during the next campaigns of LLINs in Iran.

PMID- 22592580
TI  - Cerebral sinus thrombosis in scleroderma: a case report.
AB  - Scleroderma or systemic sclerosis is a multisystem disease due to excessive
      collagen deposition in different organs and autoimmunity by production of
      autoantibodies.According to previous reports, brain is rarely affected in
      scleroderma, however recent studies show central nervous system can be affect not
      only as a complication of systemic involvement (hypertension, renal failure) but
      also as a primary manifestation. In scleroderma, thrombus formation in central
      nervous system and peripheral systems is uncommon may be due to endothelial cells
      damage which causes to release antithrombotic factors. We discuss a scleroderma
      patient with high titter of anticardiolipin antibody who developed to cerebral
      sinus thrombosis and cerebellum infarction. Then we review literature for both
      primary brain involvement and thrombotic event in systemic sclerosis.

PMID- 22592581
TI  - Concurrent peripheral pathologies and complex regional pain syndrome type 1 as
      contributors to acute post-stroke shoulder pain: a case report.
AB  - Post-stroke shoulder pain is associated with either a peripheral or central
      pathology. However, most of the time, it is challenging to establish a cause-and
      effect relationship between the suggested pathology and shoulder pain reported.
      We report a 66 year-old man who developed a right hemiplegic shoulder pain two
      months post stroke with initial investigations suggestive of peripheral
      pathologies. Pharmacological and non-pharmacological treatment did not improve
      his shoulder pain. Later he developed complex regional pain syndrome (CRPS) of
      the right hand and the initial shoulder pain subsequently relieved following
      resolution of the CRPS.

PMID- 22592582
TI  - Retrocyclin RC-101 blocks HIV-1 transmission across cervical mucosa in an organ
      culture.
AB  - BACKGROUND: Cervical tissue-based organ cultures have been used successfully to
      evaluate microbicides for toxicity and antiviral activity. The antimicrobial
      peptide retrocyclin RC-101 has been shown to have potent anti-HIV activity in
      cell culture. OBJECTIVE: To evaluate RC-101 in organ culture for toxicity and its
      ability to block HIV-1 transmission across cervical mucosa. METHODS: A cervical
      tissue-based organ culture was used to measure antiviral activity of RC-101.
      Cytotoxicity in tissues was determined by immunostaining of cellular proteins and
      by measuring inflammatory cytokines using real-time reverse transcriptase
      polymerase chain reaction and Luminex technology. RESULTS: RC-101 blocked
      transmission of both R5 and X4 HIV-1 across cervical mucosa in this organ culture
      model. Furthermore, film-formulated RC-101 exhibited potent antiviral activity in
      organ culture. Such antiviral activity of RC-101 was retained in the presence of
      semen and vaginal fluid. RC-101 showed no cytotoxicity in cervical tissue.
      Furthermore, RC-101 did not induce proinflammatory cytokine response in tissues.
      RC-101 also did not have any effect on natural killer cell activity and
      proliferation of CD4 and CD8 cells and did not show chemotactic activity.
      CONCLUSIONS: Therefore, because of strong antiviral activity and low cytotoxicity
      in cervical tissues, RC-101 should be considered as an excellent microbicide
      candidate against HIV-1.

PMID- 22592583
TI  - Transmitted drug resistance and phylogenetic relationships among acute and early
      HIV-1-infected individuals in New York City.
AB  - BACKGROUND: Transmitted drug resistance (TDR) is critical to managing HIV-1
      infected individuals and being a public health concern. We report on TDR
      prevalence and include analyses of phylogenetic clustering of HIV-1 in a
      predominantly men who have sex with men cohort diagnosed during acute/recent HIV
      1 infection in New York City. METHODS: Genotypic resistance testing was conducted
      on plasma samples of 600 individuals with acute/recent HIV-1 infection (1995
      2010). Sequences were used for resistance and phylogenetic analyses. Demographic
      and clinical data were abstracted from medical records. TDR was defined according
      to International AIDS Society-USA and Stanford HIV database guidelines.
      Phylogenetic and other analyses were conducted using PAUP*4.0 and SAS,
      respectively. RESULTS: The mean duration since HIV-1 infection was 66.5 days. TDR
      prevalence was 14.3% and stably ranged between 10.8% and 21.6% (P(trend) = 0.42).
      Nucleoside reverse transcriptase inhibitors resistance declined from 15.5% to
      2.7% over the study period (P(trend) = 0.005). M41L (3.7%), T215Y (4.0%), and
      K103N/S (4.7%) were the most common mutations. K103N/S prevalence increased from
      1.9% to 8.0% between 1995 and 2010 (P(trend) = 0.04). Using a rigorous definition
      of clustering, 19.3% (112 of 581) of subtype B viral sequences cosegregated into
      transmission clusters and clusters increased over time. There were fewer and
      smaller transmission clusters than had been reported in a similar cohort in
      Montreal but similar to reports from elsewhere. CONCLUSIONS: TDR is stable in
      this cohort and remains a significant concern to both individual patient
      management and the public health.

PMID- 22592584
TI  - Stable incidence of HIV diagnoses among Danish MSM despite increased engagement
      in unsafe sex.
AB  - BACKGROUND: Since introduction of highly active antiretroviral therapy (HAART),
      the prevalence of Danish HIV-positive men who have sex with men (MSM) has
      increased substantially. In contrast, the incidence of MSM diagnosed with HIV has
      not increased, and this paradox has been the focus of intensive debate. METHODS:
      Study period was 1995-2010. Data were obtained from 2 Danish nation-wide
      registries of HIV and syphilis, and 5 consecutive surveys on sexual behavior in
      Danish MSM. We calculated incidences of HIV and syphilis in MSM, prevalence of
      HIV-positive MSM with detectable viral load (>400 HIV RNA copies/mL), and changes
      in frequency of unprotected anal intercourse. We introduce The Cohort Community
      Reproductive Rate (CCRR) to describe the number of newly diagnosed MSM per HIV
      positive MSM per year and used Poisson regression to model CCRR. RESULTS: From
      1995 to 2010, the prevalence of Danish MSM diagnosed with HIV increased from 1035
      to 1813 (75%), whereas the number of HIV-positive MSM with detectable viral load
      (>400 HIV RNA copies/mL) decreased by 75% from 1035 to 262. The incidence of
      syphilis and unprotected anal intercourse rose dramatically in the same period,
      whereas CCRR decreased from 0.099 (95% confidence interval: 0.092 to 0.108) to
      0.071 (95% confidence interval: 0.065 to 0.079). CONCLUSIONS: Our results
      strongly indicate that HAART has decreased the risk of transmission of HIV
      despite increased practice of unsafe sex and thereby substantiate that HAART
      should be offered to MSM to reduce risk of transmission of the disease.

PMID- 22592586
TI  - Time to initiate antiretroviral therapy between 4 weeks and 12 weeks of
      tuberculosis treatment in HIV-infected patients: results from the TIME study.
AB  - BACKGROUND: Optimal timing for initiation of antiretroviral therapy (ART) among
      HIV-infected patients with tuberculosis (TB) is not well established. METHODS:
      HIV/TB-coinfected patients were randomized to initiate
      tenofovir/lamivudine/efavirenz at 4 weeks (4-week group) or 12 weeks (12-week
      group) of TB treatment. The primary outcome was 1-year all-cause mortality.
      RESULTS: Of 156 patients, 79 were in 4-week group and 77 in 12-week group.
      Overall, median (interquartile range) CD4 was 43 (47-106) cells per cubic
      millimeter and median (interquartile range) HIV-1 RNA was 5.8 (5.4-6.3) log
      copies per milliliter. Eleven (7%) mortalities occurred in a total follow-up
      period of 137 patient-years. Seven percent (6/79, 8.76 per 100 patient-years)
      mortalities were in 4-week group, and 6% (5/77, 7.25 per 100 person-years)
      mortalities were in 12-week group [relative risk (RR) = 0.845, 95% confidence
      interval (CI) = 0.247 to 2.893]. Twenty-eight (35%) patients in 4-week group and
      25 (32%) patients in 12-week group were hospitalized (RR = 1.142, 95% CI = 0.588
      to 2.217). Grade 2-4 adverse events were 39% (31/79) in 4-week group and 34%
      (26/77) in 12-week group (RR = 1.267, 95% CI = 0.659 to 2.435). In multivariate
      analysis, "low albumin" (RR = 2.695, 95% CI = 1.353 to 5.475) and "low baseline
      CD4 count" (RR = 4.878, 95% CI = 1.019 to 23.256) were the independent predictors
      of mortality. Immune reconstitution inflammatory syndrome was more frequent in 4
      week group with an incidence of 8.86 versus 5.02 per 100 person-months in 12-week
      group over the first 6 months of ART (P = 0.069). CONCLUSIONS: In middle-income
      countries where ART is initiated at CD4 count of <350 cells per cubic millimeter,
      immediate initiation of ART in HIV-infected patients with active TB was not
      associated with survival advantage when compared to initiation of ART at 12
      weeks.

PMID- 22592585
TI  - Potential cardiovascular disease risk markers among HIV-infected women initiating
      antiretroviral treatment.
AB  - BACKGROUND: Inflammation and hemostasis perturbation may be involved in vascular
      complications of HIV infection. We examined atherogenic biomarkers and
      subclinical atherosclerosis in HIV-infected adults before and after beginning
      highly active antiretroviral therapy (HAART). METHODS: In the Women's Interagency
      HIV Study, 127 HIV-infected women studied pre and post HAART were matched to HIV
      uninfected controls. Six semiannual measurements of soluble CD14, tumor necrosis
      factor (TNF) alfa, soluble interleukin (IL) 2 receptor, IL-6, IL-10, monocyte
      chemoattractant protein 1, D-dimer, and fibrinogen were obtained. Carotid artery
      intima-media thickness was measured by B-mode ultrasound. RESULTS: Relative to
      HIV-uninfected controls, HAART-naive HIV-infected women had elevated levels of
      soluble CD14 (1945 vs 1662 ng/mL, Wilcoxon signed rank P < 0.0001), TNF-alpha
      (6.3 vs 3.4 pg/mL, P < 0.0001), soluble IL-2 receptor (1587 vs 949 pg/mL, P <
      0.0001), IL-10 (3.3 vs 1.9 pg/mL, P < 0.0001), monocyte chemoattractant protein 1
      (190 vs 163 pg/mL, P < 0.0001), and D-dimer (0.43 vs 0.31 MUg/mL, P < 0.01).
      Elevated biomarker levels declined after HAART. Although most biomarkers
      normalized to HIV-uninfected levels, in women on effective HAART, TNF-alpha
      levels remained elevated compared with HIV-uninfected women (+0.8 pg/mL, P =
      0.0002). Higher post-HAART levels of soluble IL-2 receptor (P = 0.02), IL-6 (P =
      0.05), and D-dimer (P = 0.03) were associated with increased carotid artery
      intima-media thickness. CONCLUSIONS: Untreated HIV infection is associated with
      abnormal hemostasis (eg, D-dimer), proatherogenic (eg, TNF-alpha), and
      antiatherogenic (eg, IL-10) inflammatory markers. HAART reduces most inflammatory
      mediators to HIV-uninfected levels. Increased inflammation and hemostasis are
      associated with subclinical atherosclerosis in recently treated women. These
      findings have potential implications for long-term risk of cardiovascular disease
      in HIV-infected patients, even with effective therapy.

PMID- 22592587
TI  - Comorbid diabetes and the risk of progressive chronic kidney disease in HIV
      infected adults: data from the Veterans Aging Cohort Study.
AB  - INTRODUCTION: Approximately, 15% of HIV-infected individuals have comorbid
      diabetes. Studies suggest that HIV and diabetes have an additive effect on
      chronic kidney disease (CKD) progression; however, this observation may be
      confounded by differences in traditional CKD risk factors. METHODS: We studied a
      national cohort of HIV-infected and matched HIV-uninfected individuals who
      received care through the Veterans Healthcare Administration. Subjects were
      divided into 4 groups based on baseline HIV and diabetes status, and the rate of
      progression to an estimated glomerular filtration rate (eGFR) <45 mL/min/1.73m
      was compared using Cox-proportional hazards modeling to adjust for CKD risk
      factors. RESULTS: About 31,072 veterans with baseline eGFR >=45 mL/min/1.73m
      (10,626 with HIV only, 5088 with diabetes only, and 1796 with both) were followed
      for a median of 5 years. Mean baseline eGFR was 94 mL/min/1.73m, and 7%
      progressed to an eGFR < 45 mL/min/1.73m. Compared with those without HIV or
      diabetes, the relative rate of progression was increased in individuals with
      diabetes only [adjusted hazard ratio (HR) 2.48; 95% confidence interval (CI):
      2.19 to 2.80], HIV only [HR: 2.80, 95% CI: 2.50 to 3.15], and both HIV and
      diabetes [HR: 4.47, 95% CI: 3.87 to 5.17]. DISCUSSION: Compared with patients
      with only HIV or diabetes, patients with both diagnoses are at significantly
      increased risk of progressive CKD even after adjusting for traditional CKD risk
      factors. Future studies should evaluate the relative contribution of complex
      comorbidities and accompanying polypharmacy to the risk of CKD in HIV-infected
      individuals and prospectively investigate the use of cART, glycemic control, and
      adjunctive therapy to delay CKD progression.

PMID- 22592589
TI  - Provision of services and care for HIV-exposed infants: a comparison of maternal
      and child health clinic and HIV comprehensive care clinic models.
AB  - OBJECTIVE: Prevention of Mother-to-Child Transmission of HIV programs require
      follow-up of HIV-exposed infants (HEI) for infant feeding support, prophylactic
      medicines, and HIV diagnosis for at least 18 months. Retention in care and
      receipt of HIV services are challenging in resource-limited settings. This study
      compared infant follow-up results when HEI services were provided within Maternal
      and Child Health (MCH) clinics or in specialized HIV Comprehensive Care Clinics
      (CCCs) in Kenya. METHODS: This observational prospective cohort study enrolled
      HEI at 6-8 weeks of age in 2 purposively selected hospitals with similar
      characteristics but different models of service delivery. In the CCC model, HEI
      received immunization and growth monitoring in MCH but cotrimoxazole prophylaxis
      and infant HIV testing in the CCC. In the MCH model, all services were provided
      in the MCH. Data were collected at enrollment, 14 weeks, and 6, 9, and 12 months.
      RESULTS: From April 2008 to April 2009, 184 HEI were enrolled in the CCC cohort
      and 179 in the MCH cohort. Infants in MCH were 1.14, 1.42, 1.95, and 1.29 times
      more likely to attend 14-week, 6-, 9-, and 12-month postnatal visits,
      respectively, and 2.24 times (95% confidence interval: 1.57 to 3.18) more likely
      to attend all 4 visits. Although infants in MCH were 1.33 times (95% confidence
      interval: 1.10 to 1.62) more likely to have HIV antibody testing at 1 year than
      CCC, there were no differences for polymerase chain reaction test or
      cotrimoxazole initiation at 6-8 weeks. CONCLUSIONS: HIV services integrated in
      MCH yield better follow-up of HEI than CCC.

PMID- 22592588
TI  - Antiretroviral treatment interruptions predict female genital shedding of
      genotypically resistant HIV-1 RNA.
AB  - OBJECTIVES: Resistant viruses may emerge in the female genital tract during
      antiretroviral therapy (ART). Our objective was to identify predictors of drug
      resistant HIV-1 RNA in genital secretions after initiation of nonnucleoside
      reverse transcriptase inhibitor-based therapy. DESIGN: We conducted a prospective
      cohort study with periodic evaluation of plasma and genital swab samples for HIV
      1 RNA levels and antiretroviral resistance mutations. METHODS: First-line ART was
      initiated in 102 women. Plasma and genital HIV-1 RNA levels were measured at
      months 0, 3, 6, and 12. Genotypic resistance testing was performed for samples
      from all participants with RNA >1000 copies per milliliter at month 6 or 12. Cox
      regression analysis was used to identify factors associated with incident genital
      tract resistance. RESULTS: Detectable genital tract resistance developed in 5
      women, all with detectable plasma resistance (estimated incidence, 5.5/100 person
      years of observation). Treatment interruption >48 hours, adherence by pill count,
      adherence by visual analog scale, and baseline plasma viral load were associated
      with incident genital tract resistance. In multivariate analysis, only treatment
      interruption was associated with risk of detectable genital tract resistance
      (adjusted hazard ratio: 14.2; 95% confidence interval: 1.3 to 158.4).
      CONCLUSIONS: Treatment interruption >48 hours during nonnucleoside reverse
      transcriptase inhibitor-based therapy led to a significantly increased risk of
      detecting genotypically resistant HIV-1 RNA in female genital tract secretions.
      Patient- and program-level interventions to prevent treatment interruptions could
      reduce the risk of shedding-resistant HIV-1 during ART.

PMID- 22592590
TI  - Sexual frequency and planning among at-risk men who have sex with men in the
      United States:  implications for event-based intermittent pre-exposure
      prophylaxis.
AB  - Intermittent dosing of pre-exposure prophylaxis (iPrEP) has potential to decrease
      costs, improve adherence, and minimize toxicity. Practical event-based dosing of
      iPrEP requires men who have sex with men (MSM) to be sexually active on fewer
      than 3 days each week and plan for sexual activity. MSM who may be most suitable
      for event-based dosing were older, more educated, more frequently used sexual
      networking websites, and more often reported that their last sexual encounter was
      not with a committed partner. A substantial proportion of these MSM endorse high
      risk sexual activity, and event-based iPrEP may best target this population.

PMID- 22592591
TI  - Assessment of lumbar vertebrae morphology by magnetic resonance imaging in
      osteoporosis.
AB  - OBJECTIVE: To investigate the lumbar spinal morphology in patients with and
      without osteoporosis by comparing the endplate changes, intervertebral disc
      changes, and vertebral heights. DESIGN: This is a retrospective study. Medical
      records of the 3,530 patients admitted to the Physical Medicine and
      Rehabilitation outpatient clinics with low back pain between August 2010 and
      August 2011 were retrospectively reviewed. A total of 64 patients of whom 57 were
      females (89.1 %) and seven were males (10.9 %) were included in the study.
      Participants were divided into an osteoporosis group, an osteopenia group, and a
      nonosteoporotic control group, according to bone mineral densities. RESULTS: In
      this study, mid heights of L3, L4, and L5 vertebrae were found to be higher in
      the normal group than in both the osteopenic and osteoporotic groups. Mid part
      heights of L1-2, L2-3, and L5-S1 intervertebral discs were significantly lower in
      the normal group when compared to the osteopenic and osteoporotic groups. End
      plate marrow abnormality was detected in L1 lower end plate in 75 % of normal
      subjects, 40.6 % of osteopenics, and 25 % of osteoporotics. Statistically
      significant difference in the presence of Schmorl nodes in L5 vertebra lower end
      plates was present between groups; 58.3 % of normals, 34.4 % of osteopenics and
      15 % of osteoporotics had Schmorl nodes in L5 vertebra lower end plates. There
      was a significant difference regarding disc degeneration and intradiscal gas
      presence in L5-S1 intervertebral discs between groups; 66.7 % of normals, 28.1 %
      of osteopenics, and 25 % of osteoporotics had severe disc degeneration and
      intradiscal gas was present in L5-S1 intervertebral discs. CONCLUSIONS:
      Significant changes in morphology of the lumbar spine and intervertebral discs
      were found. It was revealed that the effects of osteoporosis are not limited to
      the bone but also present in the intervertebral discs. Mid heights of
      intervertebral discs were higher in the osteoporotic and osteopenic groups when
      compared to normal subjects along with the lowered mid heights of lumbar
      vertebrae. It was also observed that stronger vertebral bones were associated
      with more disc and vertebral degeneration.

PMID- 22592592
TI  - Recent advances in the total synthesis of cyclopropane-containing natural
      products.
AB  - In this tutorial review, recent advances in the synthesis of cyclopropane
      containing natural products are discussed, highlighting the application of novel
      synthetic methodologies and innovative synthetic strategies in the construction
      of highly functionalized cyclopropanes. The examples showcased herein aim to
      inspire students and practitioners of organic synthesis to seek further advances
      in the chemical synthesis of cyclopropanes, both in the context of target
      oriented syntheses and method developments.

PMID- 22592593
TI  - Synthesis of anti and syn hydroxy-iso-evoninic acids.
AB  - The first synthesis of hydroxy-iso-evoninic acid (2), a pyridyl diacid found as a
      macrodilactone bridging ligand in bioactive Celastraceae sesquiterpenoid-based
      natural products, has been achieved in 9 steps and an overall yield of 26%. The
      synthesis utilizes a benzilic ester rearrangement (BER) and a late stage benzylic
      oxidation to give access to all four stereoisomers whose absolute stereochemistry
      was assigned following chromatographic separation and anomalous dispersion X-ray
      crystallography.

PMID- 22592594
TI  - Smoking beliefs and behavior among youth in South Korea, Taiwan, and Thailand.
AB  - BACKGROUND: Beliefs about smoking are important predictors of smoking behavior
      among adolescents, and adolescents who hold positive beliefs about the benefits
      of smoking are at an increased risk of smoking initiation. An alarming fact is
      the rising smoking prevalence in Asian countries, particularly the increasing
      trend in smoking during adolescence. PURPOSE: This cross-sectional study examined
      smoking beliefs and behavior among a nationally representative sample of youth in
      South Korea, Taiwan, and Thailand. METHODS: Descriptive statistics, linear
      regression, and logistic regression methods were used to analyze data from 13-15
      year-old adolescents who participated in the 2005 Global Youth Tobacco Survey
      (GYTS) in South Korea (N = 4,765) and Thailand (N = 15,420) and the 2007 GYTS in
      Taiwan (N = 3,955). RESULTS: The rate of ever smoking among youth was similar in
      all three countries and ranged from 26.7 to 28.0 %. The prevalence of current
      smoking among youth in Thailand (11.4 %) was nearly double the prevalence in
      South Korea (6.6 %) and Taiwan (6.5 %). Pro-tobacco advertising exposure, as well
      as older ages, was a positive and significant predictor of positive beliefs about
      smoking among youth in all three countries. Additionally, youth who reported
      increased positive smoking-related beliefs, greater pro-tobacco advertising
      exposure, and were male were more likely to be current smokers in all three
      countries. CONCLUSION: Results suggest that greater attention be directed to
      understanding beliefs and attitudes about smoking among youth. Exploring the
      relationship between these factors and smoking behavior can provide a strong
      starting point in the development of effective smoking prevention interventions
      and tobacco control policies in this region.

PMID- 22592595
TI  - Multi-modality therapy for cancer of the esophagus and GE junction.
AB  - Cancers of the esophagus and gastroesophageal junction (GEJ) are associated with
      a high mortality rate. In the United States, the incidence of adenocarcinoma of
      the distal esophagus and GEJ is rising at an alarming rate. Decades of
      investigation have established the impact on survival of neoadjuvant platinum
      based chemotherapy as well as chemoradiation for locally advanced tumors. Distant
      recurrence remains the most common pattern of failure and efforts to improve
      therapeutic outcome should focus on optimizing systemic therapy. Induction
      chemotherapy before preoperative chemoradiation and postoperative adjuvant
      chemotherapy are approaches to intensify systemic therapy delivery and deserve
      further investigation. The integration of targeted therapies and development of
      predictive biomarkers to identify subgroups of patients who are likely to benefit
      will mark the future of neoadjuvant treatment in this disease.

PMID- 22592596
TI  - Management of non-melanoma skin cancer in immunocompromised solid organ
      transplant recipients.
AB  - The management of non-melanoma skin cancers (NMSCs) in solid organ transplant
      recipients (OTRs) presents a variety of clinical challenges for physicians. OTRs
      are at a 65-fold increased risk for developing cutaneous squamous cell carcinomas
      (SCC), the most common NMSC that develops after transplantation. Risk factors
      contributing to the development of NMSCs in OTRs include a past medical history
      of any previous skin cancer, a personal history of significant sun exposure and a
      fair skin complexion or phototype. Further, greater immunosuppressive medication
      levels lead to an increased risk of NMSCs. Among immunosuppressants, specific
      older agents such as azathioprine and cyclosporine may increase the risk of
      developing NMSCs in contrast to newer agents such as sirolimus. Early skin biopsy
      and treatment of premalignant and malignant lesions are essential for treating
      these patients successfully. In this regard, the concept of field cancerization
      has been instructive in broadening treatments to include entire affected areas
      rather than individual lesions given that the areas with significant ultraviolet
      irradiation will continue to develop numerous individual precancerous and
      cancerous lesions. Field therapy with photodynamic therapy or topical 5
      fluorouracil, imiquimod or diclofenac is often used in OTRs according to
      individual patient tolerability. Prompt excision or Mohs micrographic surgery is
      the standard of care of primary, uncomplicated squamous cell and basal cell
      carcinomas. For patients with in-transit or metastatic squamous cell carcinomas,
      adjuvant radiation, chemotherapy, and staging by sentinel lymph node dissection
      may be employed. For patients who develop numerous SCC per year, chemoprophylaxis
      can be effective in limiting the burden of disease. In consultation with the
      multidisciplinary transplant team, the immunosuppressive regimen can be revised
      to lower overall immunosuppression or altered to include newer drugs that have
      decreased oncogenic potential in OTRs. The greatest impact may be made by the
      prevention of NMSCs through simple, but rigorous, patient education on the
      benefits of UV protection, periodic self-skin examinations, and regular follow
      ups. Accordingly, vitamin D and calcium supplementation should also be
      incorporated in transplant recipients. Management of OTRs requires patient
      education, frequent motivation for vigilance, regular follow-up, and
      interdisciplinary collaboration between transplant surgeons, nephrologists,
      hepatologists, cardiologists, transplant nurses, dermatologists, oncologists,
      pharmacists, and other relevant physicians ideally orchestrated by the essential
      transplant coordinators.

PMID- 22592598
TI  - Efficient in vivo regulation of cytidine deaminase expression in the
      haematopoietic system using a doxycycline-inducible lentiviral vector system.
AB  - Regulated transgene expression may reduce transgene-specific and genotoxic risks
      associated with gene therapy. To prove this concept, we have investigated the
      suitability of doxycycline (Dox)-inducible human cytidine deaminase (hCDD)
      overexpression from lentiviral vectors to mediate effective myeloprotection while
      circumventing the lymphotoxicity observed with constitutive CDD activity. Rapid
      Dox-mediated transgene induction associated with a 6-17-fold increase in drug
      resistance was observed in 32D and primary murine bone marrow (BM) cells.
      Moreover, robust Dox-regulated transgene expression in the entire haematopoietic
      system was demonstrated for primary and secondary recipients of hCDD-transduced
      R26-M2rtTA transgenic BM cells. Furthermore, mice were significantly protected
      from myelosuppressive chemotherapy as evidenced by accelerated recovery of
      granulocytes (1.9+/-0.6 vs 1.3+/-0.3, P=0.034) and platelets (883+/-194 vs 584+/
      160 10(3) per MUl, P=0.011). Minimal transgene expression in the non-induced
      state and no overt cellular toxicities including lymphotoxicity were detected.
      Thus, using a relevant murine transplant model our data provide conclusive
      evidence that drug-resistance transgenes can be expressed in a regulated fashion
      in the lymphohaematopoietic system, and that Dox-inducible systems may be used to
      reduce myelotoxic side effect of anticancer chemotherapy or to avoid side effects
      of high constitutive transgene expression.

PMID- 22592597
TI  - Ethanol-induced locomotor activity in adolescent rats and the relationship with
      ethanol-induced conditioned place preference and conditioned taste aversion.
AB  - Adolescent rats exhibit ethanol-induced locomotor activity (LMA), which is
      considered an index of ethanol's motivational properties likely to predict
      ethanol self-administration, but few studies have reported or correlated ethanol
      induced LMA with conditioned place preference (CPP) by ethanol at this age. The
      present study assessed age-related differences in ethanol's motor stimulating
      effects and analyzed the association between ethanol-induced LMA and conventional
      measures of ethanol-induced reinforcement. Experiment 1 compared ethanol-induced
      LMA in adolescent and adult rats. Subsequent experiments analyzed ethanol-induced
      CPP and conditioned taste aversion (CTA) in adolescent rats evaluated for ethanol
      induced LMA. Adolescent rats exhibit a robust LMA after high-dose ethanol.
      Ethanol-induced LMA was fairly similar across adolescents and adults. As
      expected, adolescents were sensitive to ethanol's aversive reinforcement, but
      they also exhibited CPP. These measures of ethanol reinforcement, however, were
      not related to ethanol-induced LMA. Spontaneous LMA in an open field was,
      however, negatively associated with ethanol-induced CTA.

PMID- 22592600
TI  - Preferential extraction of left- or right-handed single-walled carbon nanotubes
      by use of chiral diporphyrin nanotweezers.
AB  - Handedness- and diameter-based separation of single-walled carbon nanotubes was
      achieved through preferential extraction of 76-CoMoCAT with 2,6-pyridylene
      bridged chiral diporphyrin nanotweezers.

PMID- 22592599
TI  - Sstr2A: a relevant target for the delivery of genes into human glioblastoma cells
      using fiber-modified adenoviral vectors.
AB  - Glioblastomas are the most aggressive of the brain tumors occurring in adults and
      children. Currently available chemotherapy prolongs the median survival time of
      patients by only 4 months. The low efficiency of current treatments is partly
      owing to the blood-brain barrier, which restricts the penetration of most drugs
      into the central nervous system. Locoregional treatment strategies thus become
      mandatory. In this context, viral tools are of great interest for the selective
      delivery of genes into tumoral cells. Gliomas express high levels of type 2
      somatostatin receptors (sstr2A), pinpointing them as suitable targets for the
      improvement of transduction efficiency in these tumors. We designed a new
      adenoviral vector based on the introduction of the full-length somatostatin (SRIF
      (somatotropin release-inhibiting factor)) sequence into the HI loop of the HAdV
      fiber protein. We demonstrate that (i) HAdV-5-SRIF uptake into cells is mediated
      by sstr2A, (ii) our vector drives high levels of gene expression in cells
      expressing endogenous sstr2A, with up to 65-fold enhancement and (iii) low doses
      of HAdV-5-SRIF are sufficient to infect high-grade human primary glioblastoma
      cells. Adenoviral vectors targeting SRIF receptors might thus represent a
      promising therapeutic approach to brain tumors.

PMID- 22592602
TI  - Arsenic and chromium in sea foods from Niger Delta of Nigeria: a case study of
      Warri, Delta State.
AB  - This study determined the concentration of Arsenic and Chromium in sea foods
      samples from Ethiope River. The sea foods were bought from different locations
      along the bank of the river. Arsenic concentration ranged from 0.046 +/- 0.01 to
      0.083 +/- 0.05 mg/kg, while the chromium concentration ranged from 0.079 +/- 0.04
      to 0.152 +/- 0.14 mg/kg. Palaemon serratus has the highest concentration of
      arsenic and chromium, 152 +/- 0.14 mg/kg and 0.081 +/- 0.04 mg/kg respectively,
      while Harengula jaguana has the lowest concentration of arsenic and chromium,
      0.079 +/- 0.04 mg/kg and 0.046 +/- 0.01 mg/kg respectively. There are various oil
      prospecting companies and oil and gas related industries in this area which
      discharge untreated waste products into Ethiope River. In view of this, there is
      need to determine the level of arsenic and chromium contamination of the river,
      since the inhabitants depend on the river for fishing and other domestic uses.

PMID- 22592603
TI  - A novel one-pot pseudo-five-component condensation reaction towards bifunctional
      diazepine-tetrazole containing compounds: synthesis of 1H-tetrazolyl-1H-1,4
      diazepine-2,3-dicarbonitriles and 1H-tetrazolyl-benzo[b][1,4]diazepines.
AB  - A novel and efficient method has been developed for the one-pot synthesis of
      bifunctional diazepine-tetrazole containing compounds. 1H-Tetrazolyl-1H-1,4
      diazepine-2, 3-dicarbonitrile and 1H-tetrazolyl-benzo[b][1,4]diazepine
      derivatives were synthesized in good yields using 2,3-diaminomaleonitrile or an
      aromatic diamine, ketones, trimethylsilyl azide, and an isocyanide in the
      presence of p-toluenesulfonic acid as a catalyst in methanol at room temperature.

PMID- 22592604
TI  - Magnifying endoscopy with narrow-band imaging is useful in the differential
      diagnosis between low-grade adenoma and early cancer of superficial elevated
      gastric lesions.
AB  - BACKGROUND: The usefulness of magnifying gastroscopy has been reported in
      differentiating between benign and malignant gastric mucosal lesions. However,
      there have been no studies of the usefulness of magnifying endoscopy with narrow
      band imaging (M-NBI) in the diagnosis of superficial (non-polypoid) elevated
      lesions of the stomach. In this study, we investigated the ability of M-NBI to
      differentiate between cancer and adenoma in superficial elevated lesions of the
      stomach. METHODS: We examined 93 consecutive superficial elevated lesions of the
      stomach. We defined the endoscopic criteria for early cancer as red coloring
      using conventional white light imaging (C-WLI), and an irregular microvascular
      pattern with a demarcation line, or irregular microsurface pattern with a
      demarcation line, using M-NBI. We determined the sensitivity, specificity and
      accuracy of C-WLI and M-NBI in the diagnosis of these 93 lesions. RESULTS: The
      sensitivity, specificity, and accuracy (95 % confidence interval) of C-WLI versus
      M-NBI were 64 % (52-76 %) versus 95 % (90-100 %), 94 % (86-100 %) versus 88 % (77
      99 %), and 74 % (66-83 %) versus 92 % (86-98 %), respectively. Sensitivity and
      accuracy were significantly higher for M-NBI than C-WLI. CONCLUSIONS: M-NBI
      appears to be useful in differentiating between cancerous and adenomatous
      superficial elevated lesions of the stomach.

PMID- 22592605
TI  - Cation induced structural transformation and mass spectrometric observation of
      the missing dodecavanadomanganate(IV).
AB  - The heteropolyvanadate cluster [(n-C(4)H(9))(4)N](4)[Mn(IV)V(12)O(34)].2CH(3)CN
      has been isolated by cation exchange from K(10)[(Mn(IV)V(11)O(32))(2)].20H(2)O.
      The structural transformation has been confirmed by X-ray single crystal
      structure determination and cryospray ionization mass spectrometry measurements.

PMID- 22592606
TI  - Generation of induced pluripotent stem cells from primary chronic myelogenous
      leukemia patient samples.
AB  - Induced pluripotent stem cells (iPSCs) can be generated by the expression of
      defined transcription factors not only from normal tissue, but also from
      malignant cells. Cancer-derived iPSCs are expected to provide a novel
      experimental opportunity to establish the disease model. We generated iPSCs from
      imatinib-sensitive chronic myelogenous leukemia (CML) patient samples.
      Remarkably, the CML-iPSCs were resistant to imatinib although they consistently
      expressed BCR-ABL oncoprotein. In CML-iPSCs, the phosphorylation of ERK1/2, AKT,
      and JNK, which are essential for the maintenance of both BCR-ABL (+) leukemia
      cells and iPSCs, were unchanged after imatinib treatment, whereas the
      phosphorylation of signal transducer and activator of transcription (STAT)5 and
      CRKL was significantly decreased. These results suggest that the signaling for
      iPSCs maintenance compensates for the inhibition of BCR-ABL. CML-iPSC-derived
      hematopoietic cells recovered the sensitivity to imatinib although CD34(+)38(
      )90(+)45(+) immature cells were resistant to imatinib, which recapitulated the
      pathophysiologic feature of the initial CML. CML-iPSCs provide us with a novel
      platform to investigate CML pathogenesis on the basis of patient-derived samples.

PMID- 22592607
TI  - Mutated regions of nucleophosmin 1 elicit both CD4(+) and CD8(+) T-cell responses
      in patients with acute myeloid leukemia.
AB  - Mutations in the nucleophosmin gene (NPM1(mut)) are one of the most frequent
      molecular alterations in acute myeloid leukemia (AML), and immune responses may
      contribute to the favorable prognosis of AML patients with NPM1(mut). In the
      present study, we were able to demonstrate both CD4(+) and CD8(+) T-cell
      responses against NPM1(mut). Ten peptides derived from wild-type NPM1 and
      NPM1(mut) were subjected to ELISPOT analysis in 33 healthy volunteers and 27 AML
      patients. Tetramer assays against the most interesting epitopes were performed
      and Cr(51)-release assays were used to show the cytotoxicity of peptide-specific
      T cells. Moreover, HLA-DR-binding epitopes were used to test the role of CD4(+) T
      cells in NPM1 immunogenicity. Two epitopes (epitopes #1 and #3) derived from
      NPM1(mut) induced CD8(+) T-cell responses. A total of 33% of the NPM1(mut) AML
      patients showed immune responses against epitope #1 and 44% against epitope #3.
      Specific lysis of leukemic blasts was detected. To obtain robust immune responses
      against tumor cells, the activation of CD4(+) T cells is crucial. Therefore,
      overlapping (OL) peptides were analyzed in ELISPOT assays and OL8 was able to
      activate both CD8(+) and CD4(+) T cells. The results of the present study show
      that NPM1(mut) induces specific T-cell responses of CD4(+) and CD8(+) T cells and
      therefore is a promising target for specific immunotherapies in AML.

PMID- 22592608
TI  - Immunopharmacologic response of patients with B-lineage acute lymphoblastic
      leukemia to continuous infusion of T cell-engaging CD19/CD3-bispecific BiTE
      antibody blinatumomab.
AB  - T cell-engaging CD19/CD3-bispecific BiTE Ab blinatumomab has shown an 80%
      complete molecular response rate and prolonged leukemia-free survival in patients
      with minimal residual B-lineage acute lymphoblastic leukemia (MRD(+) B-ALL).
      Here, we report that lymphocytes in all patients of a phase 2 study responded to
      continuous infusion of blinatumomab in a strikingly similar fashion. After start
      of infusion, B-cell counts dropped to < 1 B cell/MUL within an average of 2 days
      and remained essentially undetectable for the entire treatment period. By
      contrast, T-cell counts in all patients declined to a nadir within < 1 day and
      recovered to baseline within a few days. T cells then expanded and on average
      more than doubled over baseline within 2-3 weeks under continued infusion of
      blinatumomab. A significant percentage of reappearing CD8(+) and CD4(+) T cells
      newly expressed activation marker CD69. Shortly after start of infusion, a
      transient release of cytokines dominated by IL-10, IL-6, and IFN-gamma was
      observed, which no longer occurred on start of a second treatment cycle. The
      response of lymphocytes in leukemic patients to continuous infusion of
      blinatumomab helps to better understand the mode of action of this and other
      globally T cell-engaging Abs. The trial is registered with www.clinicaltrials.gov
      identifier NCT00560794.

PMID- 22592609
TI  - Computed tomography findings of influenza A (H1N1) pneumonia in adults: pattern
      analysis and prognostic comparisons.
AB  - AIM: The aim of this study was to evaluate retrospectively the chest computed
      tomography findings of influenza A (H1N1) pneumonia and their relationship with
      clinical outcome. METHODS: Chest computed tomography findings and clinical
      outcomes of 76 patients with influenza A (H1N1) pneumonia were assessed. Computed
      tomography findings were evaluated for the presence and distribution of
      parenchymal abnormalities, which were then classified into 3 patterns:
      bronchopneumonia, cryptogenic organizing pneumonia (COP), and acute interstitial
      pneumonia (AIP) patterns. Clinical courses were divided into 2 groups on the
      basis of necessitating admission to intensive care unit or mechanical ventilation
      therapy (group 1) or not (group 2). RESULTS: Lung abnormalities consisted of
      ground-glass opacity (93%, 71 patients), consolidation (66%, 50 patients), small
      nodules (61%, 46 patients), and tree-in-bud sign (22%, 17 patients). Lesions were
      classified into bronchopneumonia (49%, 37 patients), COP (30%, 23 patients), AIP
      (18%, 14 patients), and unclassifiable (3%, 2 patients) patterns. Patients with
      AIP pattern had a tendency to belonging to group 1, accounting for 40% (8 of 20
      patients) of group 1 course and only 11% (6 of 56 patients) of group 2 course (P
      = 0.004). CONCLUSIONS: Computed tomography findings of influenza A (H1N1)
      pneumonia in adults can be classified into COP, AIP, and bronchopneumonia
      patterns. Patients presenting with AIP pattern have a tendency to show poor
      prognosis.

PMID- 22592610
TI  - Computed tomographic imaging features of sudden cardiac arrest and impending
      cardiogenic shock.
AB  - We intend to describe the imaging findings of sudden cardiac arrest occurring
      during computed tomographic (CT) examination and also of impending cardiogenic
      shock in 4 patients. Despite rare reports of acute cardiac arrest occurring
      during or shortly after CT scan, CT features are quite characteristic.
      Familiarity with CT findings of these patients is essential for accurate
      interpretation of images, immediate initiation of resuscitation, as well as
      informing clinical physician in these conditions.

PMID- 22592611
TI  - High-definition computed tomography for coronary artery stents imaging compared
      with standard-definition 64-row multidectector computed tomography: an initial in
      vivo study.
AB  - OBJECTIVE: The evaluation of coronary stents by computed tomography (CT) remains
      difficult. We assessed the imaging performance of a high-definition CT scanner
      (HDCT) by comparing with a conventional 64-row standard-definition CT (SDCT).
      METHODS: One hundred thirty-eight consecutive stented patients underwent coronary
      CT angiography, among whom 66 patients were examined by HDCT, and 72 patients by
      SDCT (LightSpeed VCT XT; GE Healthcare, Waukesha, Wis). The image quality score,
      the inner stent diameter (ISD), and the radiation dose were analyzed. All data
      were statistically tested by SPSS 13.0 software (SPSS Inc, Chicago, Ill).
      RESULTS: In 72 patients examined using SDCT, 135 stents were detected; in 66
      patients examined using HDCT, 119 stents were detected. The image quality score
      on HDCT was significantly better than that on SDCT (1.4 [SD, 0.7] vs 1.9 [SD,
      0.8]). The ISD on HDCT was significantly higher than that on SDCT (1.8 [SD, 0.5]
      vs 1.6 [SD, 0.4]). There was no significant difference of either image quality
      score or ISD between the HDCT and SDCT groups in stents with 2.5-mm diameter.
      Images on HDCT showed significantly better image quality score and larger ISD
      than images on SDCT in 2.75-, 3-, and 3.5-mm stents. For patients examined by
      retrospective electrocardiogram-gated technique, the radiation dose on HDCT was
      significantly lower than that on SDCT (11.3 [SD, 2.9] vs 15.1 [SD, 3.8] mSv).
      CONCLUSIONS: High-definition CT scanner offered improved image quality and
      measurement accuracy for imaging coronary stents compared with conventional SDCT,
      providing higher spatial resolution and lower dose for evaluating coronary stents
      with 2.75- to 3.5-mm diameter.

PMID- 22592612
TI  - Washout of mass-like benign breast lesions at dynamic magnetic resonance imaging.
AB  - OBJECTIVE: This study aimed to estimate the frequency and timing of washout in a
      series of pathologically proven benign mass-like breast lesions at dynamic
      magnetic resonance imaging. METHODS: Institutional review board approval was
      obtained for this retrospective study. We evaluated enhancement kinetics of 33
      pathologically confirmed benign breast lesions: fibroadenomas (n = 22), adenosis
      (n = 6), typical ductal hyperplasia (n = 2), fibroadenoma with ductal hyperplasia
      (n = 1), fibrosclerosis (n = 1), and inflammatory lesion (n = 1). Coronal 3
      dimensional T1-weighted gradient-echo sequences were acquired before/after
      intravenous injection of 0.1 mmol/ kg gadoterate meglumine (time resolution, 111
      seconds), 1 before and 5 after contrast injection. The time point at which the
      kinetic curve demonstrated a washout was recorded. Cumulative distribution of
      lesions showing washout was built. Paired comparisons of specificity for washout
      kinetics were performed using the McNemar test. RESULTS: Of 33 lesions, washout
      was never observed in 20 (61%), whereas 13 (39%) showed washout during the study.
      Of these 13 lesions, only 1 (inflammatory mass) exhibited washout within the
      first 3 minutes (specificity, 97%), 9 within 6 minutes (specificity, 73%), and 13
      within 8 minutes (specificity, 61%). Specificity of washout kinetics within 3
      minutes (97%) was significantly larger than that from the sixth minute (73%) and
      thereafter (P < 0.016). CONCLUSIONS: A prolonged observation for dynamic breast
      magnetic resonance imaging may result in false-positive washout, especially after
      6 minutes. Late washout should not be considered a reliable marker of malignancy.

PMID- 22592613
TI  - Intrathoracic migration of a silicone breast implant 5 months after video
      assisted thoracoscopic surgery.
AB  - A 72-year-old woman, who had previous bilateral reconstruction mammoplasty,
      underwent video-assisted thoracoscopic surgery for a right middle lobe pulmonary
      carcinoid. Five months after her surgery, the patient noticed an acute pronounced
      reduction in her right breast volume, with shortness of breath and cough. A
      computed tomography study of the chest revealed intrathoracic migration and
      rupture of her right breast implant, with associated silicone thorax. Subsequent
      video-assisted thoracoscopic surgery confirmed this diagnosis.

PMID- 22592614
TI  - Skull fractures through parietal foramina:  report of two cases.
AB  - Enlarged parietal foramina are related to a condition in which defective
      intramembranous ossification of the parietal bones results in enlargement of the
      normal foramina. Although generally believed to be a benign variant, scalp
      defects, seizures, and structural brain abnormalities have been reported in a
      small percentage of affected patients. These 2 cases now present evidence that
      parietal foramina constitute structural weak spots in the calvarium that may
      potentially increase risk of skull fracture after trauma.

PMID- 22592615
TI  - Occult distal femoral physeal injury with disruption of the perichondrium.
AB  - The authors describe a case of distal femoral physeal injury with disruption of
      the perichondrium in a 9-year-old girl after a sledding accident. The patient
      presented with knee pain, limited range of motion, and inability to bear weight.
      Initial radiographs were normal. A magnetic resonance imaging of the knee
      demonstrated abnormal signal and widening of the distal femoral physis with
      elevation of the posterior distal femoral periosteum. This case illustrates the
      main magnetic resonance imaging findings in an occult Salter Harris type I
      injury: increased physeal thickness and signal intensity on water-sensitive
      sequences, perichondrial disruption, and intracartilaginous fracture.

PMID- 22592616
TI  - Differentiating radiological features of rapid- and slow-growing renal cell
      carcinoma using multidetector computed tomography.
AB  - PURPOSE: This study aimed to retrospectively evaluate the radiological features
      between rapid- and slow-growing renal cell carcinoma (RCC). MATERIALS AND
      METHODS: Twenty-five pathologically proven RCCs were reviewed with computed
      tomography (CT). Each tumor underwent at least 2 CT sessions. Growth rate was
      evaluated in terms of its maximal diameter and volume change with the serial CT
      scan. We reviewed 8 reports from 8 single-institution series in the world
      literature regarding growth rate of RCCs and determined mean growth rate. Slow-
      and rapid-growing RCCs were compared in relation to several radiological factors
      (tumor shape, initial size, initial volume, initial location, enhancement
      pattern, and cystic change). In addition, we evaluated differences in growth rate
      between asymptomatic and symptomatic RCCs. RESULTS: The mean diameter growth rate
      of RCC was determined as 0.49 cm/y (8 studies, 126 cases). There were 14 cases of
      rapid-growing RCCs (mean growth rate, 1.3 cm/y) and 11 cases of slow-growing RCCs
      (mean growth rate, 0.1 cm/y). The slow-growing tumors showed round shape, small
      initial size, small initial volume, and outer location of the kidney compared
      with the rapid-growing tumors. Sixteen patients (64%) were treated for incidental
      and 9 patients (36%) were treated for symptomatic RCCs. The asymptomatic RCCs
      grew at a slow rate both diametrically (P = 0.007) and volumetrically (P =
      0.003). CONCLUSIONS: Rapid- and slow-growing RCCs tend to show some different
      radiological features with respect to tumor shape, initial size, initial volume,
      and location. Radiological features may be helpful to predict growth rate.

PMID- 22592617
TI  - Changes of the normal ovary during menstrual cycle in reproductive age on the
      diffusion-weighted image.
AB  - OBJECTIVE: The objective of this study was to investigate changes in magnetic
      resonance findings of the normal ovary during menstrual cycle on diffusion
      weighted image (DWI). METHODS: Magnetic resonance imaging was performed in 9
      healthy females at the menstrual, periovulatory, and luteal phases using a 1.5-T
      unit. Signal intensity (SI) of the ovary on DWI with a b value of 1000 s/mm was
      visually scored. The ovary-to-muscle contrast ratios on DWI and apparent
      diffusion coefficient (ADC) values were also evaluated. RESULTS: All the ovaries
      were identified, and higher SI than the nerve root was identified in 70% (38/54)
      of the ovaries, although visual scores did not show significant difference among
      menstrual phases. The mean ADC values (10 mm/s) were 1.71 (SD, 0.27), 1.71 (SD,
      0.22), and 1.67 (SD, 0.19) in menstrual, periovulatory, and luteal phases,
      respectively. No phase-dependent change was observed in contrast ratios and ADC
      values. CONCLUSION: The normal ovary in fertile period shows high SI enough to be
      identified on DWI, and observed values are independent of the menstrual cycle.

PMID- 22592618
TI  - Comprehensive comparative study of computed tomography-based estimates of split
      renal function for potential renal donors: modified ellipsoid method and other CT
      based methods.
AB  - OBJECTIVE: To investigate a new modified computed tomographic (CT) ellipsoid
      method of split renal function and to compare results from this method with other
      CT-derived metrics. METHODS: Thirty-eight potential renal donors with both CT and
      nuclear renography were retrospectively evaluated for estimated split function
      using 6 CT methods to determine accuracy. For the CT methods, correlation,
      reproducibility, ease in image post-processing, and the ability of CT-derived
      methods to determine the dominant kidney before renal transplantation were
      evaluated using a nuclear renography reference standard. RESULTS: Four of the 6
      CT methods (split renal volume, modified ellipsoid method, parenchymal area,
      attenuation capacity) showed similar strong correlation (r = 0.84-0.79). Bland
      Altman analysis revealed similar performance in differences (SDs <3.0%) between
      those CT measures and reference standard, as well as good interobserver agreement
      for the modified ellipsoid and parenchymal area methods. The technically simpler
      methods had inferior performance. Post-processing time for the modified ellipsoid
      method was significantly shorter than semiautomated split renal volume or
      parenchymal area method (P < 0.01). Each CT-based method showed excellent
      agreement (100% or 97.4%) with renography regarding the determination of dominant
      kidney. CONCLUSIONS: Excellent correlation with nuclear split renal function
      supports the use of CT alone for the imaging assessment for many potential renal
      donors, including the decision of which kidney to harvest. Among the CT-based
      methods, the modified ellipsoid method can be performed rapidly with high
      accuracy and reproducibility.

PMID- 22592619
TI  - Massive subchorionic thrombosis followed by magnetic resonance imaging.
AB  - Massive subchorionic thrombosis is a rare condition, defined as a large thrombus
      confined to the subchorionic space. It is associated with poor perinatal
      prognosis. However, prenatal diagnosis by ultrasonography is often difficult. We
      report a case of massive subchorionic thrombosis developing dermatomyositis after
      the delivery, followed by magnetic resonance imaging. Moreover, we review other 4
      cases assessed with magnetic resonance imaging. Magnetic resonance imaging is
      very useful for confirmation of diagnosis and follow-up in combination with
      ultrasonography.

PMID- 22592620
TI  - Organ-based computed tomographic (CT) radiation dose reduction to the lenses:
      impact on image quality for CT of the head.
AB  - PURPOSE: Recently, a new specific organ dose adaption and reduction protocol, or
      SODAR tool (X-CARE, Siemens Healthcare), which reduces dose to the anterior
      aspect of the body of patients, was installed on our computed tomographic
      scanner. The purpose of this pilot project was to evaluate image quality and dose
      distribution in the acquired data with the new protocol. MATERIALS AND METHODS:
      Sixteen consecutive patients were scanned with the new SODAR head protocol. The
      findings were compared with 16 matched patients who were imaged with the standard
      computed tomographic head trauma protocol. Image quality was assessed
      qualitatively using a scale of 1 to 4 (1, excellent; 2, good; 3, fair; 4,
      nondiagnostic). Additionally, 1-cm regions of interest were placed in the white
      matter of the cerebral hemispheres, the cerebellar hemispheres, and the brain
      stem at the level of the pons for a quantitative analysis. The standard deviation
      of each measurement was recorded as an indicator for image noise. Dose
      measurement trials were performed using optically stimulated luminescence
      dosimeters on head phantoms and then on patients. RESULTS: Subjective image
      quality ranged between 1 and 3; no scan areas were considered nondiagnostic.
      Overall image quality of the posterior fossa averaged at 1.656 was slightly
      reduced compared to the cerebral hemispheres (mean, 1.141). The mean standard
      protocol brain stem image quality was 1.604, with only minimal deterioration to
      1.708 in the SODAR group.No significant difference in image noise could be found
      between the SODAR group with a mean noise of 4.515 and standard images with a
      mean of 4.721 (P > 0.05).The dose to the anterior aspect of the patient was
      lowered to 3.2 mGy compared to 4.5 mGy on the lateral aspect of the scan (P >
      0.05). To compensate for the photon loss in the posterior aspect, the dose has to
      be slightly increased to a mean of 6 mGy, but overall, a significant dose
      reduction with stable image quality could be achieved by reducing the dose length
      product from 1489 to 1347 mGy.cm using SODAR (P < 0.0001). CONCLUSION: Using the
      SODAR protocol resulted not only in an impressive 46% to 59% frontal dose
      reduction but also in the overall dose reduction. This dose reduction was
      obtained without sacrificing image quality, providing diagnostic images of the
      brain while protecting radiosensitive structures like the eye lenses in trauma
      brain imaging. Future applications will be reducing dose to other radiosensitive
      structures such as the thyroid gland and breast tissue from potentially harmful
      low-energy radiation without compromising image quality.

PMID- 22592621
TI  - Radiation dose reduction with Sinogram Affirmed Iterative Reconstruction
      technique for abdominal computed tomography.
AB  - PURPOSE: The objective of this study was to assess the effect of Sinogram
      Affirmed Iterative Reconstruction (SAFIRE) and filtered back-projection (FBP)
      techniques on abdominal computed tomography (CT) performed with 50% and 75%
      radiation dose reductions. METHODS: Twenty-four patients (mean age, 64 +/- 14
      years; male-female ratio, 10:14) gave informed consent for an institutional
      review board-approved prospective study involving acquisition of additional
      research images through the abdomen on 128-slice multi-detector-row CT (SOMATOM
      Definition Flash) at quality reference mAs of 100 (50% lower dose) and 50 (75%
      lower dose) over a scan length of 10 cm using combined modulation (CARE Dose 4D).
      Standard-of-care abdominal CT was performed at 200 quality reference mAs, with
      remaining parameters held constant. The 50- and 100-mAs data sets were
      reconstructed with FBP and at 4 SAFIRE settings (S1, S2, S3, S4). Higher number
      of SAFIRE settings denotes increased strength of the algorithm resulting in lower
      image noise. Two abdominal radiologists independently compared the FBP and SAFIRE
      images for lesion number, location, size and conspicuity, and visibility of small
      structures, image noise, and diagnostic confidence. Objective noise and
      Hounsfield units (HU) were measured in the liver and the descending aorta.
      RESULTS: All 43 lesions were detected on both FBP and SAFIRE images. Minor
      blocky, pixelated appearance of 50% and 75% reduced dose images was noted at S3
      and S4 SAFIRE but not at S1 and S2 settings. Subjective noise was suboptimal in
      both 50% and 75% lower-dose FBP images but was deemed acceptable on all SAFIRE
      settings. Sinogram Affirmed Iterative Reconstruction images were deemed
      acceptable in all patients at 50% lower dose and in 22 of 24 patients at 75%
      lower dose. As compared with 75% reduced dose FBP, objective noise was lower by
      22.8% (22.9/29.7), 35% (19.3/29.7), 44.3% (16.7/29.3), and 54.8% (13.4/29.7) on
      S1 to S4 settings, respectively (P < 0.001). CONCLUSIONS: Sinogram Affirmed
      Iterative Reconstruction-enabled reconstruction provides abdominal CT images
      without loss in diagnostic value at 50% reduced dose and in some patients also at
      75% reduced dose.

PMID- 22592622
TI  - Comparison of hybrid and pure iterative reconstruction techniques with
      conventional filtered back projection:  dose reduction potential in the abdomen.
AB  - PURPOSE: Assess the effect of filtered back projection (FBP) and hybrid (adaptive
      statistical iterative reconstruction [ASIR]) and pure (model-based iterative
      reconstruction [MBIR]) iterative reconstructions on abdominal computed tomography
      (CT) acquired with 75% radiation dose reduction. MATERIALS AND METHODS: In an
      institutional review board-approved prospective study, 10 patients (mean
      [standard deviation] age, 60 (8) years; 4 men and 6 women) gave informed consent
      for acquisition of additional abdominal images on 64-slice multidetector-row CT
      (GE 750HD, GE Healthcare). Scanning was repeated over a 10-cm scan length at 200
      and 50 milliampere second (mA s), with remaining parameters held constant at 120
      kilovolt (peak), 0.984:1 pitch, and standard reconstruction kernel. Projection
      data were deidentified, exported, and reconstructed to obtain 4 data sets (200-mA
      s FBP, 50-mA s FBP, 50-mA s ASIR, 50-mA s MBIR), which were evaluated by 2
      abdominal radiologists for lesions and subjective image quality. Objective noise
      and noise spectral density were measured for each image series. RESULTS: Among
      the 10 patients, the maximum weight recorded was 123 kg, with maximum transverse
      diameter measured as 43.7 cm. Lesion conspicuity at 50-mA s MBIR was better than
      on 50-mA s FBP and ASIR images (P < 0.01). Image noise was rated as suboptimal on
      low-dose FBP and ASIR but deemed acceptable in MBIR images. Objective noise with
      50-mA s MBIR was 2 to 3 folds lower compared to 50-mA s ASIR, 50-mA s FBP, and
      200-mA s FBP (P < 0.0001). Noise spectral density analyses demonstrated that ASIR
      retains the noise spectrum signature of FBP, whereas MBIR has much lower noise
      with a more regularized noise spectrum pattern. CONCLUSION: Model-based iterative
      reconstruction renders acceptable image quality and diagnostic confidence in 50-
      mA s abdominal CT images, whereas FBP and ASIR images are associated with
      suboptimal image quality at this radiation dose level.

PMID- 22592624
TI  - Amniotic membrane: from structure and functions to clinical applications.
AB  - Amniotic membrane (AM) or amnion is a thin membrane on the inner side of the
      fetal placenta; it completely surrounds the embryo and delimits the amniotic
      cavity, which is filled by amniotic liquid. In recent years, the structure and
      function of the amnion have been investigated, particularly the pluripotent
      properties of AM cells, which are an attractive source for tissue
      transplantation. AM has anti-inflammatory, anti-bacterial, anti-viral and
      immunological characteristics, as well as anti-angiogenic and pro-apoptotic
      features. AM is a promoter of epithelialization and is a non-tumorigenic tissue
      and its use has no ethical problems. Because of its attractive properties, AM has
      been applied in several surgical procedures related to ocular surface
      reconstruction and the genito-urinary tract, skin, head and neck, among others.
      So far, the best known and most auspicious applications of AM are ocular surface
      reconstruction, skin applications and tissue engineering. However, AM can also be
      applied in oncology. In this area, AM can prevent the delivery of nutrients and
      oxygen to cancer cells and consequently interfere with tumour angiogenesis,
      growth and metastasis.

PMID- 22592623
TI  - Deformable anatomic templates embed knowledge into patient's brain images: Part
      1. Construction and display.
AB  - OBJECTIVE: This paper describes the methods used to create annotated deformable
      anatomic templates (DATs) and display them in a patient's axial 2-dimensional and
      reformatted volume brain images. METHODS: A senior neuroradiologist annotated and
      manually segmented 1185 color-coded structures on axial magnetic resonance images
      of a normal template brain using domain knowledge from multiple medical
      specialties. Besides the visible structures, detailed pathways for vision,
      speech, cognition, and movement were charted. This was done by systematically
      joining visible anatomic anchor points and selecting the best fit based on
      comparisons with cadaver dissections and the constraints defined on the companion
      2-dimensional images. RESULTS: The DAT is commercially available for use on a
      picture archiving and communication system or as a standalone workstation.
      CONCLUSIONS: The DAT can quickly embed extensive, clinically useful functional
      neuroanatomic knowledge into the patient's brain images. Besides labeling visible
      structures, DAT displays clinically important, previously uncharted subdivisions
      of the fiber tracts.

PMID- 22592625
TI  - Achieving CNS axon regeneration by manipulating convergent neuro-immune
      signaling.
AB  - After central nervous system (CNS) trauma, axons have a low capacity for
      regeneration. Regeneration failure is associated with a muted regenerative
      response of the neuron itself, combined with a growth-inhibitory and cytotoxic
      post-injury environment. After spinal cord injury (SCI), resident and
      infiltrating immune cells (especially microglia/macrophages) contribute
      significantly to the growth-refractory milieu near the lesion. By targeting both
      the regenerative potential of the axon and the cytotoxic phenotype of
      microglia/macrophages, we may be able to improve CNS repair after SCI. In this
      review, we discuss molecules shown to impact CNS repair by affecting both immune
      cells and neurons. Specifically, we provide examples of pattern recognition
      receptors, integrins, cytokines/chemokines, nuclear receptors and galectins that
      could improve CNS repair. In many cases, signaling by these molecules is complex
      and may have contradictory effects on recovery depending on the cell types
      involved or the model studied. Despite this caveat, deciphering convergent
      signaling pathways on immune cells (which affect axon growth indirectly) and
      neurons (direct effects on axon growth) could improve repair and recovery after
      SCI. Future studies must continue to consider how regenerative therapies
      targeting neurons impact other cells in the pathological CNS. By identifying
      molecules that simultaneously improve axon regenerative capacity and drive the
      protective, growth-promoting phenotype of immune cells, we may discover SCI
      therapies that act synergistically to improve CNS repair and functional recovery.

PMID- 22592626
TI  - The composition, protein genesis and significance of the inner acrosomal membrane
      of eutherian sperm.
AB  - As a consequence of the acrosomal reaction during fertilization, the inner
      acrosomal membrane (IAM) becomes exposed and forms the leading edge of the sperm
      for adhesive binding to and subsequent penetration of the zona-pellucida (ZP) of
      the metaphase-II-arrested oocyte. A premise of this review is that the IAM of
      spermatozoa anchors receptors and enzymes (on its extracellular side) that are
      required for sperm attachment to and penetration of the ZP. We propose a sperm
      cell fractionation strategy that allows for direct access to proteins bound to
      the extracellular side of the IAM. We review the types of integral and peripheral
      IAM proteins that have been found by this approach and that have been implicated
      in ZP recognition and lysis. We also propose a scheme for the origin and assembly
      of these proteins within the developing acrosome during spermiogenesis. During
      development, the extravesicular side of the membrane of the acrosomic vesicle is
      coated by peripheral proteins that transport and bind this secretory vesicle to
      the spermatid nucleus. The part of the membrane that binds to the nucleus becomes
      the IAM, while its extravesicular protein coat, which is retained between the IAM
      and the nuclear envelope of spermatozoa becomes the subacrosomal layer of the
      perinuclear theca (SAL-PT). Another premise of this review is that the IAM of
      spermatozoa is bound with proteins (on its intracellular side), namely the SAL-PT
      proteins, which hold the clue to the mechanism of acrosomal-nuclear docking. We
      propose a sperm cell fractionation strategy that allows for direct access to SAL
      PT proteins. We then review the types of SAL-PT proteins that have been found by
      this approach and that have been implicated in transporting and binding the
      acrosome to the sperm nucleus.

PMID- 22592627
TI  - Dual role of lipoproteins in endothelial cell dysfunction in atherosclerosis.
AB  - The endothelium is a key constituent of the vascular wall, being actively
      involved in maintaining the structural integrity and proper functioning of blood
      vessels. Hyperlipidemia, diabetes, hypertension, smoking and aging are important
      risk factors for the dysfunction of endothelial cells (EC). Circulating
      lipoproteins (Lp) synthesized and secreted from the intestine or liver have an
      important role in supplying peripheral tissues with fatty acids from triglyceride
      rich lipoproteins (TGRLp) for energy production or storage, and cholesterol from
      low density lipoproteins (LDL) or high density lipoproteins (HDL) for the
      synthesis of cellular membranes and steroid hormones. Under pathological
      conditions, Lp may suffer alterations in concentration and composition and become
      aggressors for EC. Modified LDL, remnant Lp, TGRLp lipolysis products,
      dysfunctional HDL are involved in the changes induced in EC morphology (reduced
      glycocalyx, overdeveloped endoplasmic reticulum, Golgi apparatus and basement
      membrane), loose intercellular junctions, increased oxidative and inflammatory
      stress, nitric oxide/redox imbalance, excess Lp transport and storage, as well as
      loss of anti-thrombotic properties, all of these being characteristics of
      endothelial dysfunction. Normal HDL are able to counteract the harmful effects of
      atherogenic Lp in EC but under persistent pathological conditions they lose the
      protective properties and become pro-atherogenic. This review summarises recent
      advances in understanding the role of Lp in the induction of endothelial
      dysfunction and the initiation and progression of atherosclerotic lesions. Its
      main focus is the antagonistic role of atherogenic Lp (LDL, VLDL, dysfunctional
      HDL) versus anti-atherogenic Lp (HDL), also pointing out the potential targets
      for arresting or reversing this process.

PMID- 22592628
TI  - Molecular and cellular mechanisms underlying the role of blood vessels in spinal
      cord injury and repair.
AB  - Spinal cord injury causes immediate damage of nervous tissue accompanied by the
      loss of motor and sensory function. The limited self-repair ability of damaged
      nervous tissue underlies the need for reparative interventions to restore
      function after spinal cord injury. Blood vessels play a crucial role in spinal
      cord injury and repair. Injury-induced loss of local blood vessels and a
      compromised blood-brain barrier contribute to inflammation and ischemia and thus
      to the overall damage to the nervous tissue of the spinal cord. Lack of
      vasculature and leaking blood vessels impede endogenous tissue repair and limit
      prospective repair approaches. A reduction of blood vessel loss and the
      restoration of blood vessels so that they no longer leak might support recovery
      from spinal cord injury. The promotion of new blood vessel formation (i.e., angio
      and vasculogenesis) might aid repair but also incorporates the danger of
      exacerbating tissue loss and thus functional impairment. The delicate interplay
      between cells and molecules that govern blood vessel repair and formation
      determines the extent of damage and the success of reparative interventions. This
      review deals with the cellular and molecular mechanisms underlying the role of
      blood vessels in spinal cord injury and repair.

PMID- 22592629
TI  - Interaction between regulatory T cells and cancer stem cells.
AB  - The concept that cancer stem cells (CSCs)/tumor stem cells/cancer-initiating
      cells are one of the key centers to cure neoplastic disease has drawn an
      increasing attention recent years. Because of their high resistance and potential
      to initiate tumors, CSCs are considered a critical factor associated with tumor
      relapse. Regulatory T(T(reg)) cells, a group of immune cells with tumor-promoting
      effect, exert their function through inhibition of effector T cells and
      regulation of the tumor microenvironment by producing a series of soluble
      factors. However, the interactions between T(reg)s and CSCs are less understood.
      The mechanisms of how T(reg)s, as tumor-promoting cells, manipulate CSCs remain
      obscure. In this review, we elucidate their interactions.

PMID- 22592630
TI  - Intestinal pH and gastrointestinal transit profiles in cystic fibrosis patients
      measured by wireless motility capsule.
AB  - BACKGROUND AND AIMS: The effect of the cystic fibrosis transmembrane conductance
      regulator protein (CFTR) defect in pancreatic insufficient (PI) patients with
      cystic fibrosis (CF) on the gastrointestinal pH profile is poorly defined.
      Adequate and efficient neutralization of the gastric acidity in the duodenum is
      important for nutrient absorption and timely release of pancreatic enzyme
      replacement therapy (PERT). We utilized a wireless motility capsule (WMC) to
      study intestinal pH profile and gastrointestinal transit profile in CF subjects.
      METHODS: WMC studies were done on ten adult CF patients with PI while off acid
      suppression medication and ten age, gender and BMI matched healthy controls. Mean
      pH over 1 min increments and area under the pH curve over 5 min increments was
      calculated for the first hour post gastric emptying. Paired t-test was used to
      compare means of the pH recordings, transit profiles and analysis of time
      interval required to reach and maintain pH >5.5 and 6.0. RESULTS: A statistically
      significant difference was observed between mean pH values during the first 23
      min of small bowel transit (p < 0.05). In CF subjects, there was a significant
      delay in time interval required to reach and sustain pH 5.5 and pH 6.0 (p <
      0.001), which is required for PERT dissolution. Only small bowel transit in CF
      subjects was noted to be significantly delayed (p = 0.004) without a compensatory
      increase in whole gut transit time. CONCLUSIONS: We have demonstrated a
      significant delay in the small intestinal transit and a deficient buffering
      capacity required to neutralize gastric acid in the proximal small bowel of
      patients with CF.

PMID- 22592631
TI  - Elevation of alanine transaminase and markers of liver fibrosis after a mixed
      meal challenge in individuals with type 2 diabetes.
AB  - BACKGROUND: Hyperalimentation for 4 weeks is associated with raised liver enzymes
      and liver fat content (LFC), which are two common features found in individuals
      with diabetes. AIM: We evaluated the effect of two mixed meal challenges on LFC,
      liver enzymes and serum bio-markers of liver injury and fibrosis in 16 healthy
      volunteers (HV) and subjects with type 2 diabetes (T2DM). METHODS: Subjects (HV:
      9 male, 7 female, aged 57.9 +/- 1.7 years, body mass index (BMI) 27.1 kg/m(2);
      and T2DM: 11 male, 5 female, aged 62.1 +/- 1.3 years, BMI 28.0 +/- 0.4 kg/m(2))
      consumed two meals at 1 h (884 kcal) and at 6 h (1,096 kcal). LFC determined by
      (1)H magnetic resonance spectroscopy, serum levels of liver enzymes, hyaluronic
      acid (HA), procollagen III N-terminal peptide (P3NP) and tissue inhibitor
      metalloproteinase-1 (TIMP-1) were estimated at time 0 (fasting) and 9 h
      (postprandial). RESULTS: Fasting LFC was higher in the T2DM group 7.6 % (4.9,
      15.4) [median (inter-quartile range)] than in the HV group 2.3 % (0.8, 5.1) (p <
      0.05) while levels of HA, P3NP and TIMP-1 were similar. Following the meal
      challenge there was no significant change in LFC. Subjects with T2DM had higher
      post-prandial rise in alanine transaminase (ALT) (p = 0.014), serum HA (p =
      0.007) and P3NP (p = 0.015) compared with HV. Fasting LFC correlated with a
      greater post-prandial increase in P3NP levels in all subjects (Pearson
      correlation r = 0.53, p = 0.001). CONCLUSIONS: In subjects with T2DM, a mixed
      meal challenge is associated with a significant elevation in the serum levels of
      ALT, HA and P3NP without significant changes in LFC. These markers should be
      performed in the fasted state.

PMID- 22592632
TI  - Global trends in infective endocarditis epidemiology.
AB  - The global epidemiology of infective endocarditis is becoming better understood
      with the initiation of multi-center collaborative studies and with an increasing
      number of case series being reported from countries outside North America and
      Europe. However, there are still many knowledge gaps and a lack of population
      based data. For endocarditis in developed countries, the role of rheumatic heart
      disease as a predisposing factor is diminishing; the population is increasingly
      elderly, staphylococci are becoming much more important pathogens, and
      proportionally more are healthcare-associated. In developing countries, the
      epidemiology of infective endocarditis remains similar to North America and
      Europe from the middle of the twentieth century, affecting a younger age group,
      is often associated with rheumatic heart disease, and is predominantly caused by
      streptococci.

PMID- 22592634
TI  - Reduced defense of central blood volume during acute lower body negative pressure
      induced hypovolemic circulatory stress in aging women.
AB  - Elderly humans are more vulnerable to trauma and hemorrhage than young and
      elderly men and respond with decreased defense of central blood volume during
      acute experimental hypovolemia induced by lower body negative pressure (LBNP).
      However, these defense mechanisms have not been evaluated in elderly women. The
      aim of this study was to determine the effectiveness of compensatory responses to
      defend central blood volume during experimental hypovolemia in elderly and young
      women. Cardiovascular responses in 34 women, 12 elderly (66 +/- 1 years) and 22
      young women (23 +/- 0.4 years), were studied during experimental hypovolemia
      induced by LBNP of 11 to 44 mmHg. Air plethysmography was used to assess the
      capacitance response (redistribution of peripheral venous blood to the central
      circulation) as well as net capillary fluid transfer from tissue to blood in the
      arm. Lower body negative pressure seemed to create comparable hypovolemia
      measured as total calf volume increase in elderly and young women. Heart rate
      increased less in elderly women (LBNP of 44 mmHg: 20 +/- 2 vs. 37 +/- 4%; P <
      0.01) but with similar (%) increase in forearm vascular resistance. Mobilization
      of capacitance blood from the peripheral circulation was both slower and
      decreased by ~60% in elderly women (P < 0.001), and net capillary fluid
      absorption from surrounding tissues was reduced by ~40% (P < 0.01, LBNP of 44
      mmHg). Elderly women responded with less increase in heart rate but with equal
      forearm vascular resistance (%) response during LBNP. Furthermore, the
      compensatory capacitance response was both slower and substantially decreased,
      and net capillary fluid absorption considerably reduced, collectively indicating
      less efficiency to defend central blood volume in elderly than in young women.

PMID- 22592633
TI  - Early intervention on the outcomes in critically ill cancer patients admitted to
      intensive care units.
AB  - PURPOSE: To determine whether earlier intervention was associated with decreased
      mortality in critically ill cancer patients admitted to an intensive care unit
      (ICU). METHODS: A retrospective observational study was performed of 199
      critically ill cancer patients admitted to the ICU from the general ward between
      January 2010 and December 2010. A logistic regression model was used to adjust
      for potential confounding factors in the association between time to intervention
      and in-hospital mortality. RESULTS: In-hospital mortality was 52 %, with a median
      Simplified Acute Physiology Score 3 (SAPS 3) of 80 [interquartile range (IQR) 67
      93], and a median Sequential Organ Failure Assessment (SOFA) score of 8 (IQR 5
      11). Median time from physiological derangement to intervention (time to
      intervention) prior to ICU admission was 1.5 (IQR 0.6-4.3) h. Median time to
      intervention was significantly shorter in survivors than in non-survivors (0.9
      vs. 3.0 h; p < 0.001). Additionally, the mortality rates increased significantly
      with increasing quartiles of time to intervention (p < 0.001, test for trend).
      Other factors associated with in-hospital mortality were severity of illness,
      performance status, hematologic malignancy, stem-cell transplantation, presence
      of three or more abnormal physiological variables, time from derangement to ICU
      admission, presence of infection, need for mechanical ventilation and
      vasopressor, and low PaO(2)/FiO(2) ratio. Even after adjusting for potential
      confounding factors, time to intervention was still significantly associated with
      hospital mortality (adjusted odds ratio 1.445, 95 % confidence interval 1.217
      1.717). CONCLUSIONS: Early intervention before ICU admission was independently
      associated with decreased in-hospital mortality in critically ill cancer patients
      admitted to the ICU.

PMID- 22592635
TI  - Inhibition of proinflammatory cytokines by SCH79797, a selective protease
      activated receptor 1 antagonist, protects rat kidney against ischemia-reperfusion
      injury.
AB  - Renal ischemia-reperfusion injury (I/R) is the most common cause of acute renal
      failure. It is partially mediated by thrombin as it is attenuated by thrombin
      inhibition or deletion of its receptor protease-activated receptor 1 (PAR1).
      However, the role of PAR1 in renal I/R injury needs to be further elucidated. The
      present study investigated the effect of PAR1 antagonist, SCH79797 (SCH), on
      renal protection and downstream effectors involved. Male Wistar rats were
      pretreated with SCH (25 MUg/kg i.p.) or vehicle, 15 min before 45 min of clamping
      of left renal pedicle after right nephrectomy. To investigate the involvement of
      phosphatidylinositol 3-kinase (PI3K)/Akt, a group of rats was subjected to
      pretreatment with an inhibitor of PI3K/Akt (LY 29004, 3 mg/kg i.p.) before renal
      ischemia and SCH treatment. A sham-operated group served as control and received
      saline. All rats were killed 24 h after reperfusion or sham operation, and blood
      samples collected and kidney tissues processed either for immunostaining and
      histological assessment or for biochemical analysis. SCH79797 markedly attenuated
      kidney damage histologically and by improving serum creatinine. Both plasma and
      protein expression of P selectin were markedly reduced as well as neutrophil
      infiltration, cytokine-induced neutrophil chemoattractant 1, and tumor necrosis
      factor alpha. These protective effects of blocking PAR1 receptor were abolished
      by preadministration of LY29004. These results suggest that PAR1 mediates renal
      I/R injury and that blocking PAR1 using SCH limits renal injury by an anti
      inflammatory effect possibly signaling via PI3K/Akt.

PMID- 22592636
TI  - A protective role for inflammasome activation following injury--Shock 2012;37(1):
      47-55.

PMID- 22592638
TI  - High Na intake increases renal angiotensin II levels and reduces expression of
      the ACE2-AT(2)R-MasR axis in obese Zucker rats.
AB  - High sodium intake is known to regulate the renal renin-angiotensin system (RAS)
      and is a risk factor for the pathogenesis of obesity-related hypertension. The
      complex nature of the RAS reveals that its various components may have opposing
      effects on natriuresis and blood pressure regulation. We hypothesized that high
      sodium intake differentially regulates and shifts a balance between opposing
      components of the renal RAS, namely, angiotensin-converting enzyme (ACE)-ANG II
      type 1 ANG II receptor (AT(1)R) vs. AT(2)-ACE2-angiotensinogen (Ang) (1-7)-Mas
      receptor (MasR), in obesity. In the present study, we evaluated protein and/or
      mRNA expression of angiotensinogen, renin, AT(1A/B)R, ACE, AT(2)R, ACE2, and MasR
      in the kidney cortex following 2 wk of a 8% high-sodium (HS) diet in lean and
      obese Zucker rats. The expression data showed that the relative expression
      pattern of ACE and AT(1B)R increased, renin decreased, and ACE2, AT(2)R, and MasR
      remained unaltered in HS-fed lean rats. On the other hand, HS intake in obese
      rats caused an increase in the cortical expression of ACE, a decrease in ACE2,
      AT(2)R, and MasR, and no changes in renin and AT(1)R. The cortical levels of ANG
      II increased by threefold in obese rats on HS compared with obese rats on normal
      salt (NS), which was not different than in lean rats. The HS intake elevated mean
      arterial pressure in obese rats (27 mmHg) more than in lean rats (16 mmHg). This
      study suggests that HS intake causes a pronounced increase in ANG II levels and a
      reduction in the expression of the ACE2-AT(2)R-MasR axis in the kidney cortex of
      obese rats. We conclude that such changes may lead to the potentially unopposed
      function of AT(1)R, with its various cellular and physiological roles, including
      the contribution to the pathogenesis of obesity-related hypertension.

PMID- 22592640
TI  - Intravenous renal cell transplantation for rats with acute and chronic renal
      failure.
AB  - Acute kidney injury (AKI) and chronic renal failure (CKD) are the most
      challenging problems in nephrology. Multiple therapies have been attempted but
      these interventions have minimal effects on the eventual outcomes, and all too
      often the result is end-stage renal disease (ESRD). The only effective therapy
      for ESRD is renal transplantation but only a small fraction of patients receive
      transplants. In this work we introduce a novel approach to transplantation
      designed to regenerate kidneys afflicted by severe AKI or CKD: intravenous renal
      cell transplantation (IRCT) with adult rat primary renal cells reprogrammed to
      express the SAA gene localized and engrafted in kidneys of rat recipients that
      had severe AKI or CKD. IRCT significantly resolved renal dysfunction and limited
      kidney damage, inflammation, and fibrosis. Severe CKD was successfully improved
      by IRCT using kidney cells from donor rats or by renal cell self-donation in a
      form of autotransplantation. We propose that IRCT with adult primary renal cells
      reprogrammed to express the SAA gene can be used to effectively treat AKI and
      CKD.

PMID- 22592639
TI  - SK but not IK channels regulate human detrusor smooth muscle spontaneous and
      nerve-evoked contractions.
AB  - Animal studies suggest that the small (SK) and intermediate (IK) conductance
      Ca(2+)-activated K(+) channels may contribute to detrusor smooth muscle (DSM)
      excitability and contractility. However, the ability of SK and IK channels to
      control DSM spontaneous phasic and nerve-evoked contractions in human DSM remains
      unclear. We first investigated SK and IK channels molecular expression in native
      human DSM and further assessed their functional role using isometric DSM tension
      recordings and SK/IK channel-selective inhibitors. Quantitative PCR experiments
      revealed that SK3 channel mRNA expression in isolated DSM single cells was ~12-
      to 44-fold higher than SK1, SK2, and IK channels. RT-PCR studies at the single
      cell level detected mRNA messages for SK3 channels but not SK1, SK2, and IK
      channels. Western blot and immunohistochemistry analysis further confirmed
      protein expression for the SK3 channel and lack of detectable protein expression
      for IK channel in whole DSM tissue. Apamin (1 MUM), a selective SK channel
      inhibitor, significantly increased the spontaneous phasic contraction amplitude,
      muscle force integral, phasic contraction duration, and muscle tone of human DSM
      isolated strips. Apamin (1 MUM) also increased the amplitude of human DSM
      electrical field stimulation (EFS)-induced contractions. However, TRAM-34 (1
      MUM), a selective IK channel inhibitor, had no effect on the spontaneous phasic
      and EFS-induced DSM contractions suggesting a lack of IK channel functional role
      in human DSM. In summary, our molecular and functional studies revealed that the
      SK, particularly the SK3 subtype, but not IK channels are expressed and regulate
      the spontaneous and nerve-evoked contractions in human DSM.

PMID- 22592641
TI  - TDAG51 mediates epithelial-to-mesenchymal transition in human proximal tubular
      epithelium.
AB  - Epithelial-to-mesenchymal transition (EMT) contributes to renal fibrosis in
      chronic kidney disease. Endoplasmic reticulum (ER) stress, a feature of many
      forms of kidney disease, results from the accumulation of misfolded proteins in
      the ER and leads to the unfolded protein response (UPR). We hypothesized that ER
      stress mediates EMT in human renal proximal tubules. ER stress is induced by a
      variety of stressors differing in their mechanism of action, including
      tunicamycin, thapsigargin, and the calcineurin inhibitor cyclosporine A. These ER
      stressors increased the UPR markers GRP78, GRP94, and phospho-eIF2alpha in human
      proximal tubular cells. Thapsigargin and cyclosporine A also increased cytosolic
      Ca(2+) concentration and T cell death-associated gene 51 (TDAG51) expression,
      whereas tunicamycin did not. Thapsigargin was also shown to increase levels of
      active transforming growth factor (TGF)-beta1 in the media of cultured human
      proximal tubular cells. Thapsigargin induced cytoskeletal rearrangement, beta
      catenin nuclear translocation, and alpha-smooth muscle actin and vinculin
      expression in proximal tubular cells, indicating an EMT response. Subconfluent
      primary human proximal tubular cells were induced to undergo EMT by TGF-beta1
      treatment. In contrast, tunicamycin treatment did not produce an EMT response.
      Plasmid-mediated overexpression of TDAG51 resulted in cell shape change and beta
      catenin nuclear translocation. These results allowed us to develop a two-hit
      model of ER stress-induced EMT, where Ca(2+) dysregulation-mediated TDAG51
      upregulation primes the cell for mesenchymal transformation via Wnt signaling and
      then TGF-beta1 activation leads to a complete EMT response. Thus the release of
      Ca(2+) from ER stores mediates EMT in human proximal tubular epithelium via the
      induction of TDAG51.

PMID- 22592642
TI  - Danthron triggers ROS and mitochondria-mediated apoptotic death in C6 rat glioma
      cells through caspase cascades, apoptosis-inducing factor and endonuclease G
      multiple signaling.
AB  - This research focused on the induction of cytotoxic effects by danthron, a
      natural anthraquinone derivative on C6 rat glioma cells through exploring the
      means of cell death and the effects on mitochondrial function. We found that
      danthron decreased the percentage of viable C6 cells and induced cell
      morphological changes in a dose-and time-dependent manner. The morphological and
      nuclei changes (DAPI staining) in C6 cells were observed using a contrast
      microscope and fluorescence microscopy, respectively. The results suggest that
      cell death of C6 cells which are induced by danthron is closely related to
      apoptotic death. Danthron decreased the level of mitochondrial membrane potential
      (DeltaPsi( m )), stimulated the release of cytochrome c from mitochondria to
      cytosol and promoted the levels of caspase-9 and caspase-3, or induced the
      release of AIF and Endo G from mitochondria. Based on both observations, we
      suggest that the danthron-provoked apoptotic death of C6 cells is mediated
      through the mitochondria-dependent pathway. Furthermore, our results also
      indicated that danthron triggered apoptosis through reactive oxygen species (ROS)
      production which were increased after 1 h exposure of danthron, which was
      reversed by the ROS scavenger N-acetyl-L: -cysteine (NAC). As a consequence,
      danthron-mediated cell death of C6 cells via ROS production, mitochondrial
      transmembrane potential collapse and releases of cytochrome c, AIF and Endo G.
      Taken together, danthron was demonstrated to be effective in killing C6 rat
      glioma cells via the ROS-promoted and mitochondria-dependent apoptotic pathways.

PMID- 22592643
TI  - Apocynum venetum leaf extract attenuates disruption of the blood-brain barrier
      and upregulation of matrix metalloproteinase-9/-2 in a rat model of cerebral
      ischemia-reperfusion injury.
AB  - We investigated the neuroprotective effects of Apocynum venetum leaf extract
      (AVLE) on a rat model of cerebral ischemia-reperfusion injury and explored the
      underlying mechanisms. Rats were randomly divided into five groups: sham,
      ischemia-reperfusion, AVLE125, AVLE250, and AVLE500. Cerebral ischemia was
      induced by 1.5 h of occlusion of the middle cerebral artery. Cerebral infarct
      area was measured by tetrazolium staining at 24 and 72 h after reperfusion, and
      neurological function was evaluated at 24, 48 and 72 h after reperfusion.
      Pathological changes on the ultrastructure of the blood-brain barrier (BBB) were
      observed by transmission electron microscopy. BBB permeability was assessed by
      detecting leakage of Evan's blue (EB) dye in brain tissue. The expression and
      activities of matrix metalloproteinase (MMP)-9/-2 were measured by western blot
      analyses and gelatin zymography at 24 h after reperfusion. AVLE (500 mg/kg/day)
      significantly reduced cerebral infarct area, improved recovery of neurological
      function, relieved morphological damage to the BBB, reduced water content and EB
      leakage in the brain, and downregulated the expression and activities of MMP-9/
      2. These findings suggest that AVLE protects against cerebral ischemia
      reperfusion-induced injury by alleviating BBB disruption. This action may be due
      to its inhibitory effects on the expression and activities of MMP-9/-2.

PMID- 22592644
TI  - Protective role of Brassica olerecea and Eugenia jambolana extracts against H2O2
      induced cytotoxicity in H9C2 cells.
AB  - This study assesses the efficacy of anthocyanin rich Brassica olerecea leaves
      (ARCE) and flavonoid rich Eugenia jambolana seed (EJSE) extracts as possible
      cardioprotective agents against hydrogen peroxide (H(2)O(2)) induced cytotoxicity
      in H9C2 cells. Presence of ARCE or EJSE resulted in a superior cell viability and
      cell integrity as revealed by cell viability and lactate dehydrogenase release
      assays and acridine orange and ethidium bromide staining of control and H(2)O(2)
      treated H9C2 cells. These extracts were also able to reduce the impact of
      H(2)O(2) induced lipid peroxidation and depletion of intracellular glutathione.
      Also, there was an increase in mitochondrial membrane potential and reduced
      generation of intracellular reactive oxygen species following ARCE or EJSE
      treatments. These results suggest that ARCE and EJSE are capable of
      cardioprotective activity due to the high number of anthocyanins and flavonoids
      in them that are instrumental in lowering intracellular oxidative stress,
      preventing depletion of cellular antioxidants and improving cell viability.

PMID- 22592646
TI  - Bone adaptation in osteoporosis.
AB  - Osteoporosis is a clinical manifestation of fracture from weakened bone tissues.
      Fracture is the result of incompatibility between biomechanical loading forces
      and material properties of bone tissues. Bone tissues constantly renew themselves
      and renovate microstructurally in responding to physiopathological changes. This
      kind of adaptation evolves as human lifestyles progress to modernization and as
      medicinal therapeutics advance to individualization. Realization of the bone
      tissues' adaptation broadens the choices for therapeutic approaches and the
      utilization of combinational treatments for the sake of not only prolonging life
      span but also improving life quality.

PMID- 22592649
TI  - Upstream process optimization of polyhydroxybutyrate (PHB) by Alcaligenes latus
      using two-stage batch and fed-batch fermentation strategies.
AB  - This research focused on optimizing the upstream process time for production of
      polyhydroxybutyrate (PHB) from sucrose by two-stage batch and fed-batch
      fermentation with Alcaligenes latus ATCC 29714. The study included selection of
      strain, two-stage batch fermentations with different time points for switching to
      nitrogen limited media (14, 16 or 18 h) and fed-batch fermentations with varied
      time points (similar to two stage) for introducing nitrogen limited media. The
      optimal strain to produce PHB using sucrose as carbon source was A. latus ATCC
      29714 with maximum-specific growth rate of 0.38 +/- 0.01 h(-1) and doubling time
      of 1.80 +/- 0.05 h. Inducing nitrogen limitation at 16 h and ending second stage
      at 26 h gave optimal performance for PHB production, resulting in a PHB content
      of 46.7 +/- 12.2 % (g PHB per g dry cell weight) at the end of fermentation. This
      was significantly higher (P <= 0.05) (approximately 7 %) than the corresponding
      fed batch run in which nitrogen limitation was initiated at 16 h.

PMID- 22592645
TI  - Peripheral axons of the adult zebrafish maxillary barbel extensively remyelinate
      during sensory appendage regeneration.
AB  - Myelination is a cellular adaptation allowing rapid conduction along axons. We
      have investigated peripheral axons of the zebrafish maxillary barbel (ZMB), an
      optically clear sensory appendage. Each barbel carries taste buds, solitary
      chemosensory cells, and epithelial nerve endings, all of which regenerate after
      amputation (LeClair and Topczewski [2010] PLoS One 5:e8737). The ZMB contains
      axons from the facial nerve; however, myelination within the barbel itself has
      not been established. Transcripts of myelin basic protein (mbp) are expressed in
      normal and regenerating adult barbels, indicating activity in both maintenance
      and repair. Myelin was confirmed in situ by using toluidine blue, an anti-MBP
      antibody, and transmission electron microscopy (TEM). The adult ZMB contains ~180
      small-diameter axons (<2 MUm), approximately 60% of which are myelinated.
      Developmental myelination was observed via whole-mount immunohistochemistry 4-6
      weeks postfertilization, showing myelin sheaths lagging behind growing axons.
      Early-regenerating axons (10 days postsurgery), having no or few myelin layers,
      were disorganized within a fibroblast-rich collagenous scar. Twenty-eight days
      postsurgery, barbel axons had grown out several millimeters and were organized
      with compact myelin sheaths. Fiber types and axon areas were similar between
      normal and regenerated tissue; within 4 weeks, regenerating axons restored ~85%
      of normal myelin thickness. Regenerating barbels express multiple promyelinating
      transcription factors (sox10, oct6 = pou3f1; krox20a/b = egr2a/b) typical of
      Schwann cells. These observations extend our understanding of the zebrafish
      peripheral nervous system within a little-studied sensory appendage. The
      accessible ZMB provides a novel context for studying axon regeneration, Schwann
      cell migration, and remyelination in a model vertebrate.

PMID- 22592650
TI  - Fine needle aspiration and core needle biopsy in the diagnosis of lymphadenopathy
      of unknown aetiology.
AB  - The clarification of enlarged lymph nodes is a common issue in clinical routine.
      By now, open surgery with complete lymph node extirpation, followed by
      histopathology, is considered as standard. We investigated the value of fine
      needle aspiration (FNA) and core needle biopsy (CNB) when supporting the
      conventional morphology by immunotyping. In total, 101 lymph nodes (reactive, n =
      19; lymphoma, n = 46; metastatic, n = 36) were examined. CNB specimens were
      sufficient for unequivocal diagnosis by histopathology in 95 %. The FNA cytology
      allowed a correct diagnosis in 49 %. When supported by immunocytology, the
      success rate improved to 72 %. By accepting "suspicious of" as correct diagnosis,
      the ratio increased to 91 %. Additional use of flow cytometry in 46 samples
      minimized the "suspicious of" diagnoses and increased the proportion of
      unequivocal diagnoses in FNA specimens to 87 %. Flow cytometry allowed a correct
      subtyping in 20 of 21 B cell lymphoma but recognised only one of five Hodgkin
      lymphoma. All eight reactive samples were correctly diagnosed by flow cytometry.
      In summary, CNB allows a reliable clarification of an unclear lymphadenopathy.
      FNA is a powerful first diagnostic approach, especially if cytology is supported
      by immunocytology. The most substantial contribution of flow cytometry in FNA is
      the discrimination between reactive lymphadenopathy and B cell lymphoma.

PMID- 22592651
TI  - Induction chemotherapy versus palliative treatment for acute myeloid leukemia in
      a consecutive cohort of elderly patients.
AB  - A retrospective survey of 210 consecutive patients aged >= 65 years (median age
      69 years, range 65-88 years) with acute myeloid leukemia (AML) diagnosed at a
      single center over a 6-year period (January 2001 to December 2006) is presented.
      De novo AML was diagnosed in 179 (85.2 %) patients and 31 (14.7 %) patients had a
      secondary AML. Twenty-three patients had M0 (11 %), 36 M1 (17.15 %), 57 M2 (27.1
      %), eight M3 (3.8 %), 45 M4 (21.4 %), 31 M5 (14.8 %), one M6 (0.5 %), one M7 (0.5
      %), and eight patients had unclassified myeloid leukemia (3.8 %) according to
      French-American-British (FAB) Study Group Classification. Eight patients with M3
      (acute promyelocytic leukemia) were excluded from the study. Cytogenetic analysis
      was performed in 172/202 (85 %) patients. The normal karyotype was found in
      81/172 (47 %), high risk aberrations in 32/172 (18.6 %), and favorable karyotype
      in 13/172 (7.5 %) patients. Supportive and palliative therapies were applied in
      115 (56.9 %) patients, a no induction chemotherapy (NIC) group, and 87 (43.1 %)
      patients received induction chemotherapy (IC group). Complete remission (CR) was
      achieved in 45/87 (51.7 %) in the IC group and in 5/115 (4.3 %) in the NIC group
      of patients. After a median follow up of 4 years, 194 (96 %) patients died. The
      variables significantly associated with a longer overall survival (OS) by
      univariate analysis were an age of <75 years, a better ECOG performance status
      (PS) (p = 0.000, CI 95.0 %, 1.358-2.049), a serum LDH activity <600 U/l (p =
      0.000, CI 95.0 %, 1.465-2.946), lower white blood cell (WBC) count at diagnosis
      (p = 0.011, CI 95.0 %, 1.102-2.100), lower comorbidity HCT-CI index (p = 0.000,
      CI 95 % 2.209-3.458), absence of splenomegaly (p = 0.015, CI 95.0 %, 1.082-2.102)
      and hepatomegaly (p = 0.008, CI 95.0 %, 1.125-2.171), and no preceding
      nonhematological malignancy. Multivariate analysis showed that significant
      factors affecting OS in the IC group were achievement of CR (p = 0.000), the ECOG
      PS (p = 0.045) and the ECOG PS (p = 0.000), and HCT-CI (p = 0.000) in the NIC
      group of elderly patients. The present study suggests that a subgroup of elderly
      patients with both ECOG PS and HCT-CI <= 2 at presentation may be eligible for
      intensive induction chemotherapy.

PMID- 22592652
TI  - Central nervous system involvement of primary cutaneous diffuse large B cell
      lymphoma-leg type diagnosed according to the WHO 2008 classification.

PMID- 22592653
TI  - Specific compartmental analysis of cartilage status in double-bundle ACL
      reconstruction patients: a comparative study using pre- and postoperative MR
      images.
AB  - PURPOSE: The purpose of this study was to evaluate the changes in the site
      specific cartilage status after a double-bundle ACL reconstruction using
      preoperative and follow-up MR images. METHODS: Thirty-six knees that underwent a
      double-bundle ACL reconstruction from 2001 to 2009 with the available
      preoperative and follow-up magnetic resonance imaging were included. Patients
      with a meniscal injury were compared with those without a meniscal injury. The
      cartilage morphology was classified using a 6-grade scale [from 0 = normal
      thickness and signal, to 6 = diffuse full-thickness loss (>75 % of the region)].
      The changes in cartilage status were evaluated at 14 sites. RESULTS: Cartilage
      changes were observed in all sites and were classified according to the site and
      degree of change. The majority of changes were grade 0 and 1, which accounted for
      68 and 16.8 % of changes, respectively. The patella medial facet and
      anterolateral and centromedial femoral regions showed significantly more
      cartilage loss than the posteromedial, centrolateral, anterolateral, and
      anteromedial tibial regions. No significance was observed between the knees with
      or without combined injuries (n.s.). On the other hand, knees with or without
      combined injuries showed a different pattern of cartilage change, as demonstrated
      by different levels of grade change at sites. CONCLUSIONS: The change in
      cartilage status was minimal after a double-bundle ACL reconstruction. The
      patella medial facet, lateral femur anterior region, and medial femur central
      region showed significantly more cartilage loss than the medial tibia posterior,
      lateral tibia central, lateral tibia anterior, and medial tibia anterior regions.
      The presence of a combined injury did not affect the cartilage status changes,
      even though it was underpowered and too short term to assess the influence of the
      meniscal injury. LEVEL OF EVIDENCE: Case series, Level IV.

PMID- 22592655
TI  - TNF-alpha and IL-10 promoter polymorphisms, HPV infection, and cervical cancer
      risk.
AB  - Although the implication of genetic factors in cervical cancer development
      remains to be elucidated, accumulative epidemiological evidence suggests that
      polymorphisms of cytokine genes may be involved in the etiology of cervical
      carcinoma. Tumor necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) are
      two multifunctional cytokines implicated in inflammation, immunity, and cellular
      organization, and were proposed to play important roles in cancer biology. In
      order to determine whether IL-10 -1082 (G/A) and TNF-alpha -238 (G/A) and -308
      (G/A) polymorphisms are associated with susceptibility to cervical cancer, a case
      control study of 122 cancer patients and 176 healthy controls was conducted.
      Cervical samples were genotyped for both TNF-alpha polymorphisms by PCR-RFLP
      assay. SNP-1082 from IL-10 gene was genotyped using pyrosequencing technology.
      The association between cervical cancer risk and the studied SNPs was evaluated
      by logistic regression. Under univariate analysis, none of these polymorphisms
      appeared associated with susceptibility of cervical cancer development or HPV
      infection. However, individuals carrying heterozygous genotype for TNF-alpha -238
      polymorphism seem to be at lower risk for cervical cancer development, with
      borderline significance (OR = 0.42, P = 0.069), as well as those carrying
      heterozygous genotypes for IL-10 and TNF-alpha -238 (OR = 0.40, P = 0.08). In
      conclusion, these results suggest a potential effect of TNF-alpha -238 G/A in the
      reduction of cervical cancer risk in Argentine women, but not TNF-alpha -308 or
      IL-10. Larger studies are needed to fully understand the genetic predisposition
      for the development of cervical cancer.

PMID- 22592656
TI  - Identification of genes regulated by the EWS/NR4A3 fusion protein in
      extraskeletal myxoid chondrosarcoma.
AB  - Approximately 75 % of extraskeletal myxoid chondrosarcoma tumors (EMC) harbor a
      t(9;22) chromosome translocation generating an EWS/NR4A3 fusion protein that is
      thought to be instrumental in the tumoral process. Current evidence suggests that
      one function of the fusion protein is to overexpress target genes. We have
      generated an in vitro human cellular model in which the fusion protein is
      expressed in mesenchymal bone marrow stem cells. We have performed microarray
      analyses of these cells and identified several genes overexpressed in the
      presence of EWS/NR4A3 which are also overexpressed in EMC tumors. These genes and
      their products represent potential therapeutic targets for EMC tumors.

PMID- 22592657
TI  - New cis-regulatory elements in the Rht-D1b locus region of wheat.
AB  - Fifteen gene-containing BACs with accumulated length of 1.82-Mb from the Rht-D1b
      locus region were sequenced and compared in detail with the orthologous regions
      of rice, sorghum, and maize. Our results show that Rht-D1b represents a conserved
      genomic region as implied by high gene sequence identity, good maintenance of
      gene colinearity, and the presence of multiple conserved noncoding sequences
      (CNSs) that are shared by other grass species. Eight cis-regulatory elements in
      these CNSs around grass DELLA genes were detected.

PMID- 22592658
TI  - A novel blast resistance gene, Pi54rh cloned from wild species of rice, Oryza
      rhizomatis confers broad spectrum resistance to Magnaporthe oryzae.
AB  - The dominant rice blast resistance gene, Pi54 confers resistance to Magnaporthe
      oryzae in different parts of India. In our effort to identify more effective
      forms of this gene, we isolated an orthologue of Pi54 named as Pi54rh from the
      blast-resistant wild species of rice, Oryza rhizomatis, using allele mining
      approach and validated by complementation. The Pi54rh belongs to CC-NBS-LRR
      family of disease resistance genes with a unique Zinc finger (C(3)H type) domain.
      The 1,447 bp Pi54rh transcript comprises of 101 bp 5'-UTR, 1,083 bp coding region
      and 263 bp 3'-UTR, driven by pathogen inducible promoter. We showed the
      extracellular localization of Pi54rh protein and the presence of glycosylation,
      myristoylation and phosphorylation sites which implicates its role in signal
      transduction process. This is in contrast to other blast resistance genes that
      are predicted to be intracellular NBS-LRR-type resistance proteins. The Pi54rh
      was found to express constitutively at basal level in the leaves, but upregulates
      3.8-fold at 96 h post-inoculation with the pathogen. Functional validation of
      cloned Pi54rh gene using complementation test showed high degree of resistance to
      seven isolates of M. oryzae collected from different geographical locations of
      India. In this study, for the first time, we demonstrated that a rice blast
      resistance gene Pi54rh cloned from wild species of rice provides broad spectrum
      resistance to M. oryzae hence can be used in rice improvement breeding programme.

PMID- 22592659
TI  - Subgenomic analysis of microRNAs in polyploid wheat.
AB  - In this study, a survey of miRNAs using the next-generation sequencing data was
      performed at subgenomic level. After analyzing shotgun sequences from chromosome
      4A of bread wheat (Triticum aestivum L.), a total of 68 different miRNAs were
      predicted in silico, of which 37 were identified in wheat for the first time. The
      long arm of the chromosome was found to harbor a higher variety (51) and
      representation (3,928) of miRNAs compared with the short arm (49; 2,226). Out of
      the 68 miRNAs, 32 were detected to be common to both arms, revealing the presence
      of separate miRNA clusters in the two chromosome arms. The differences in degree
      of representation of the different miRNAs were found to be highly variable,
      ranging 592-fold, which may have an effect on target regulation. Targets were
      retrieved for 62 (out of 68) of wheat-specific, newly identified miRNAs indicated
      that fundamental aspects of plant morphology such as height and flowering were
      predicted to be affected. In silico expression blast analysis indicated 24 (out
      of 68) were found to give hits to expressed sequences. This is the first report
      of species- and chromosome-specific miRNAs.

PMID- 22592660
TI  - MHC class I expression in HPV positive and negative tonsillar squamous cell
      carcinoma in correlation to clinical outcome.
AB  - Human papillomavirus (HPV) is an important factor for the development of
      tonsillar squamous cell carcinoma (TSCC). In addition, patients with HPV-positive
      TSCC have a better clinical outcome than patients with HPV-negative TSCC.
      Although, HPV is an important prognostic marker, additional biomarkers are needed
      to better predict clinical outcome to individualize treatment. Hence, we examined
      if classical HLA HLA-A,B,C and nonclassical HLA-E,G could serve as such marker.
      Formalin-fixed paraffin-embedded TSCC from 150 patients diagnosed 2000-2006,
      earlier analyzed for HPV DNA and p16(INK4a), and treated with intention to cure
      were evaluated for the expression of HLA-A,B,C and HLA-E,G by
      immunohistochemistry. For HPV-positive TSCC a low expression of HLA-A,B,C,
      whereas for HPV-negative TSCC, a normal expression of HLA-A,B,C was significantly
      correlated to a favorable clinical outcome. These correlations were more
      pronounced for membrane staining of HLA-A,B,C when compared with cytoplasmatic
      staining. No significant correlation was found between HLA-E,G and HPV status or
      clinical outcome. The unexpected contrasting correlation between HLA-A,B,C
      expression, and clinical outcome depending on HPV, indicates essential
      differences between HPV-positive and HPV-negative TSCC. Furthermore, our data
      demonstrate that for both HPV-positive and HPV-negative TSCC, the expression of
      HLA-A,B,C together with HPV may serve as a useful biomarker for predicting
      clinical outcome.

PMID- 22592661
TI  - Implicit memory in Korsakoff's syndrome: a review of procedural learning and
      priming studies.
AB  - Korsakoff's syndrome (KS) is characterized by dense anterograde amnesia resulting
      from damage to the diencephalon region, typically resulting from chronic alcohol
      abuse and thiamine deficiency. This review assesses the integrity of the implicit
      memory system in KS, focusing on studies of procedural learning and priming. KS
      patients are impaired on several measures of procedural memory, most likely due
      to impairment in cognitive functions associated with alcohol-related neural
      damage outside of the diencephalon. The pattern of performance on tasks of
      implicit priming suggests reliance on a residual, non-flexible memory operating
      more or less in an automatic fashion. Our review concludes that whether measures
      of implicit memory reveal intact or impaired performance in individuals with KS
      depends heavily on specific task parameters and demands, including timing between
      stimuli, the specific nature of the stimuli used in a task, and the integrity of
      supportive cognitive functions necessary for performance.

PMID- 22592662
TI  - Effects of alkali stress on growth, free amino acids and carbohydrates metabolism
      in Kentucky bluegrass (Poa pratensis).
AB  - Soil alkalization is one of the most prominent adverse environmental factors
      limiting plant growth, while alkali stress affects amino acids and carbohydrates
      metabolism. The objective of this study was conducted to investigate the effects
      of alkali stress on growth, amino acids and carbohydrates metabolism in Kentucky
      bluegrass (Poa pratensis). Seventy-day-old plants were subjected to four pH
      levels: 6.0 (control), 8.0 (low), 9.4 (moderate) and 10.3 (severe) for 7 days.
      Moderate to severe alkali stress (pH >9.4) caused a significant decline in turf
      quality and growth rate in Kentucky bluegrass. Soluble protein was unchanged in
      shoots, but decreased in roots as pH increased. The levels of amino acids was
      kept at the same level as control level at 4 days after treatment (DAT) in
      shoots, but greater at 7 DAT, when plants were subjected to severe (pH 10.3)
      alkali stress. The alkali stressed plants had a greater level of starch, water
      soluble carbohydrate and sucrose content, but lower level of fructose and
      glucose. Fructan and total non-structural carbohydrate (TNC) increased at 4 DAT
      and decreased at 7 DAT for alkali stressed plants. These results suggested that
      the decrease in fructose and glucose contributed to the growth reduction under
      alkali stress, while the increase in amino acids, sucrose and storage form of
      carbohydrate (fructan, starch) could be an adaptative mechanism in Kentucky
      bluegrass under alkali stress.

PMID- 22592663
TI  - An evaluation of the combined effects of phenolic endocrine disruptors on
      vitellogenin induction in goldfish Carassius auratus.
AB  - Phenolic compounds are widely distributed in the natural environment, typically
      existing as a mixture at the nanogram or microgram per liter level. Among the
      phenolic compounds, 4-nonylphenol, 4-t-octylphenol, bisphenol A and 2,4
      dichlorophenol attract the most concern due to their abundance and risks within
      the natural environment. The former three chemicals are known as endocrine
      disruptors causing feminization in various organisms, whereas the latter one
      requires further clarification concerning its feminization effect. This study
      aims to evaluate the combined effects of these chemicals using vitellogenin
      protein induction in male juvenile goldfish Carassius auratus as an endpoint
      after 15 days of exposure. The results showed that all these chemicals can induce
      vitellogenin with a relative potency of 4-t-octylphenol > bisphenol A > 4
      nonylphenol ? 2,4-dichlorophenol. 2,4-dichlorophenol showed a very weak
      estrogenic effect with an induction of vitellogenin concentration of <1 % of
      positive control, and it is therefore omitted in further tests to evaluate their
      combined effect. The other three chemicals were mixed in two ways, at an
      equipotent ratio and at an equal environmental level ratio, and their combined
      effects were evaluated with both the toxicity units method and concentration
      addition model. The resulting effect of exposure to both mixtures showed that
      these chemicals generally exhibited an additive effect. The ecological risk of
      phenolic chemicals may therefore be underestimated if based on the presence of
      single chemicals whereas their combined effects warrant further consideration.

PMID- 22592664
TI  - Facilitation of sympathetic neurotransmission by phosphatidylinositol-4,5
      bisphosphate-dependent regulation of KCNQ channels in rat mesenteric arteries.
AB  - Sympathetic nerves regulate vascular tone by releasing neurotransmitters into the
      vasculature. We previously demonstrated that bradykinin facilitates sympathetic
      neurotransmission in rat mesenteric arteries. Although little is known about the
      intracellular mechanism modulating this neurotransmission, recent cell line
      experiments have shown that the KCNQ channel, which is inhibited by the depletion
      of membrane phosphatidylinositol-4,5-bisphosphate (PIP2), participates in the
      control of neurotransmission by bradykinin. In the present study, we examined the
      mechanism regulating neurotransmitter release from rat perivascular sympathetic
      nerves. Excitatory junction potentials (EJPs) elicited by repetitive nerve
      stimulation (1 Hz, 11 pulses, 20 MUs, 20-50 V), a measure of sympathetic
      purinergic neurotransmission, were recorded with a conventional microelectrode
      technique in rat mesenteric arteries. Bradykinin (10-7  mol l-1) significantly
      enhanced the amplitude of EJPs (n=22, P<0.05). This enhancing effect was
      abolished by N-type calcium-channel inhibition with omega-conotoxin GVIA (2 * 10
      9 mol -1l, n=8). The blockade of phospholipase C with U-73122 (10(-6) mol l-1,
      n=17) also eliminated the facilitatory effect of bradykinin. In addition, the
      effects of bradykinin were diminished by the prevention of PIP2 resynthesis with
      wortmannin (10-5 mol l-1 n=7) or KCNQ channel inhibition with XE-991 (10-5 mol l
      1, n=7). On the other hand, depletion of intracellular calcium stores with
      cyclopiazonic acid (3 * 10-6 mol l-1, n=6) or the inhibition of protein kinase C
      with bisindolylmaleimide-I (10-6 mol l-1, n=9) did not alter the action of
      bradykinin. These data demonstrate that the hydrolysis of PIP2 by phospholipase
      C, which is activated by G(q/11)-coupled receptors, and subsequent KCNQ channel
      inhibition enhance sympathetic purinergic neurotransmission presumably via the
      activation of N-type calcium channels in rat mesenteric arteries.

PMID- 22592665
TI  - Additive renoprotective effects of aliskiren on angiotensin receptor blocker and
      calcium channel blocker treatments for type 2 diabetic patients with albuminuria.
AB  - This open-label, randomized, parallel-controlled study investigated the effects
      of the direct renin inhibitor aliskiren on 64 hypertensive type 2 diabetic
      patients with chronic kidney disease (CKD) and stable glycemic control who were
      already being treated with fixed doses of antihypertensive agents over a 24-week
      period. These agents were 80 mg of the angiotensin II receptor blocker (ARB)
      telmisartan and 5 mg of the calcium channel blocker (CCB) amlodipine. Patients
      were randomly assigned to two groups: the aliskiren group, receiving 150 mg per
      day aliskiren, which was increased to 300 mg per day (n=32), and the CCB group,
      which received an increased dose (7.5 mg per day) of amlodipine that was
      increased to 10 mg per day (n=32). Urinary albumin excretion and urinary levels
      of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and liver-type fatty acid-binding protein
      (L-FABP) were investigated in each group. Mean systolic and diastolic blood
      pressure decreased significantly in both groups, but there was no significant
      difference between the two groups at the end of the study. Serum creatinine
      levels and estimated glomerular filtration rate did not differ significantly
      between the two groups, but percent changes of urinary albumin/creatinine ratios,
      8-OHdG and L-FABP levels decreased significantly in the aliskiren group compared
      with the CCB group. Plasma aldosterone levels were significantly decreased in the
      aliskiren group, which correlated significantly with those of urinary 8-OHdG and
      L-FABP. Our results suggest that the addition of aliskiren to the maximal
      recommended dose of ARB and usual dose of amlodipine is more effective in
      reducing albuminuria and oxidant stress in hypertensive diabetic patients with
      CKD than increasing the dose of amlodipine.

PMID- 22592666
TI  - The obesity-related polymorphism PCSK1 rs6235 is associated with essential
      hypertension in the Han Chinese population.
AB  - Proprotein convertase subtilisin/kexin-type 1 (PCSK1) is a prohormone convertase
      that has an important role in prohormone maturation including the process of
      prorenin to renin. We studied the association of the PCSK1 single-nucleotide
      polymorphism (SNP) rs6235 (encoding an S690T substitution) with essential
      hypertension (EH), obesity and related traits in the Han Chinese population. The
      rs6235 SNP in the PCSK1 gene was investigated using a case-control study design,
      with 1034 hypertension cases and 1112 normotensive controls. In this study, the
      rs6235 SNP was significantly associated with hypertension (OR=1.26, 95% CI (1.10
      1.46), P=0.001); the odds ratios of GC vs GG and CC vs GG were 1.30 (95% CI (1.06
      1.58), P=0.010) and 1.55 (95% CI (1.12-2.13), P=0.007), respectively. In the
      controls, the C-allele was associated with increased systolic (P=0.010) and
      diastolic (P=0.010) blood pressure levels. In all of the EH patients and EH
      patients without a history of renin-angiotensin-aldosterone (RAA) system-related
      antagonists, the C-allele was associated with increased plasma renin activity
      (P=0.00004 and 0.002, respectively) and aldosterone levels (P=0.018 and 0.005,
      respectively). The C-allele was also associated with increased body mass index
      (BMI) (P=0.010) in the normotensive controls. In conclusion, the PCSK1 SNP rs6235
      was associated with EH and blood pressure in the Han Chinese population, and this
      association may be mediated by the SNP's effect on RAA levels. rs6235 was also
      associated with BMI in this population.

PMID- 22592667
TI  - Common variants of the UMOD promoter associated with blood pressure in a
      community-based Chinese cohort.
AB  - Hypertension is an important risk factor for chronic kidney disease. The kidney,
      in turn, has an important role in the regulation of blood pressure (BP). On the
      basis of a genome-wide association study, single-nucleotide polymorphisms in the
      uromodulin (UMOD) promoter region had been considered to influence both renal
      sodium reabsorption and BP. In this study, we asked whether common variants
      across the UMOD gene influence BP in a community-based Chinese cohort. We
      screened seven common variants across the UMOD locus in a community-based
      population from Beijing, including 1000 individuals with 48% males and an average
      age of 63.7+/-9.0 years. The urinary UMOD concentration was measured by enzyme
      linked immunosorbent assay. We then analyzed the association of common variants
      of UMOD with BP. The UMOD promoter common variant rs13333226 G/A is associated
      with diastolic BP (DBP), and G allele carriers have higher DBP compared with A/A
      homozygotes (P=0.035). The variant rs6497476 C/T predicted the DBP level, with C
      homozygotes having a higher DBP compared with CT heterozygotes and T homozygotes
      (P=0.025). Urinary UMOD excretion was correlated with urinary sodium excretion
      (R=0.239, P=0.656*10(-13)). We determined that common variants of UMOD are
      associated with DBP level in a community-based Chinese cohort.

PMID- 22592669
TI  - [Evaluation of a cell block method in cytological diagnostics].
AB  - BACKGROUND: Cell block procedures have now become an established part of
      cytological diagnostics. In this study a cytoblock technique based on the plasma
      thrombin method was evaluated. MATERIALS AND METHODS: In total 389 consecutive
      cytological samples were initially analyzed by the classical procedure and then
      by the cell block technique. The latter was done by centrifugation of the
      remaining material of the cytological sample, resuspension of the cells in blood
      plasma followed by generation of a cell clot by the addition of thrombin.
      RESULTS: Analysis of material from the peritoneal cavity, ascites and pleura was
      successful in more than 90% of cases. In 272 samples the conventional and cell
      block analyses revealed concordant results according to Papanicolaou
      classification. In 23 cases the cell block analysis induced an upgrade. In
      particular, malignant processes (PAP V) or precursor lesions (PAP IV) were
      identified in 9 cases which were not diagnosed by conventional analysis.
      CONCLUSIONS: Advantages of this method include the assessment of an additional
      sample volume and thus reduction of sampling error, the possibility for unlimited
      storage and molecular testing similar to histological samples.

PMID- 22592671
TI  - Training health professionals in smoking cessation.
AB  - BACKGROUND: Cigarette smoking is one of the leading causes of preventable death
      world wide. There is good evidence that brief interventions from health
      professionals can increase smoking cessation attempts. A number of trials have
      examined whether skills training for health professionals can lead them to have
      greater success in helping their patients who smoke. OBJECTIVES: To determine the
      effectiveness of training health care professionals in the delivery of smoking
      cessation interventions to their patients, and to assess the additional effects
      of training characteristics such as intervention content, delivery method and
      intensity. SEARCH METHODS: The Cochrane Tobacco Addiction Group's Specialised
      Register, electronic databases and the bibliographies of identified studies were
      searched and raw data was requested from study authors where needed. Searches
      were updated in March 2012. SELECTION CRITERIA: Randomized trials in which the
      intervention was training of health care professionals in smoking cessation.
      Trials were considered if they reported outcomes for patient smoking at least six
      months after the intervention. Process outcomes needed to be reported, however
      trials that reported effects only on process outcomes and not smoking behaviour
      were excluded. DATA COLLECTION AND ANALYSIS: Information relating to the
      characteristics of each included study for interventions, participants, outcomes
      and methods were extracted by two independent reviewers. Studies were combined in
      a meta-analysis where possible and reported in narrative synthesis in text and
      table. MAIN RESULTS: Of seventeen included studies, thirteen found no evidence of
      an effect for continuous smoking abstinence following the intervention. Meta
      analysis of 14 studies for point prevalence of smoking produced a statistically
      and clinically significant effect in favour of the intervention (OR 1.36, 95% CI
      1.20 to 1.55, p= 0.004). Meta-analysis of eight studies that reported continuous
      abstinence was also statistically significant (OR 1.60, 95% CI 1.26 to 2.03, p=
      0.03).Healthcare professionals who had received training were more likely to
      perform tasks of smoking cessation than untrained controls, including: asking
      patients to set a quit date (p< 0.0001), make follow-up appointments (p<
      0.00001), counselling of smokers (p< 0.00001), provision of self-help material
      (p< 0.0001) and prescription of a quit date (p< 0.00001). No evidence of an
      effect was observed for the provision of nicotine gum/replacement therapy.
      AUTHORS' CONCLUSIONS: Training health professionals to provide smoking cessation
      interventions had a measurable effect on the point prevalence of smoking,
      continuous abstinence and professional performance. The one exception was the
      provision of nicotine gum or replacement therapy, which did not differ between
      groups.

PMID- 22592672
TI  - Speech and language therapy for aphasia following stroke.
AB  - BACKGROUND: Aphasia is an acquired language impairment following brain damage
      that affects some or all language modalities: expression and understanding of
      speech, reading and writing. Approximately one-third of people who have a stroke
      experience aphasia. OBJECTIVES: To assess the effectiveness of speech and
      language therapy (SLT) for aphasia following stroke. SEARCH METHODS: We searched
      the Cochrane Stroke Group Trials Register (last searched June 2011), MEDLINE
      (1966 to July 2011) and CINAHL (1982 to July 2011). In an effort to identify
      further published, unpublished and ongoing trials we handsearched the
      International Journal of Language and Communication Disorders (1969 to 2005) and
      reference lists of relevant articles and contacted academic institutions and
      other researchers. There were no language restrictions. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) comparing SLT (a formal intervention that
      aims to improve language and communication abilities, activity and participation)
      with (1) no SLT; (2) social support or stimulation (an intervention that provides
      social support and communication stimulation but does not include targeted
      therapeutic interventions); and (3) another SLT intervention (which differed in
      duration, intensity, frequency, intervention methodology or theoretical
      approach). DATA COLLECTION AND ANALYSIS: We independently extracted the data and
      assessed the quality of included trials. We sought missing data from
      investigators. MAIN RESULTS: We included 39 RCTs (51 randomised comparisons)
      involving 2518 participants in this review. Nineteen randomised comparisons (1414
      participants) compared SLT with no SLT where SLT resulted in significant benefits
      to patients' functional communication (standardised mean difference (SMD) 0.30,
      95% CI 0.08 to 0.52, P = 0.008), receptive and expressive language. Seven
      randomised comparisons (432 participants) compared SLT with social support and
      stimulation but found no evidence of a difference in functional communication.
      Twenty-five randomised comparisons (910 participants) compared two approaches to
      SLT. There was no indication of a difference in functional communication.
      Generally, the trials randomised small numbers of participants across a range of
      characteristics (age, time since stroke and severity profiles), interventions and
      outcomes. Suitable statistical data were unavailable for several measures.
      AUTHORS' CONCLUSIONS: Our review provides some evidence of the effectiveness of
      SLT for people with aphasia following stroke in terms of improved functional
      communication, receptive and expressive language. However, some trials were
      poorly reported. The potential benefits of intensive SLT over conventional SLT
      were confounded by a significantly higher dropout from intensive SLT. More
      participants also withdrew from social support than SLT interventions. There was
      insufficient evidence to draw any conclusion regarding the effectiveness of any
      one specific SLT approach over another.

PMID- 22592673
TI  - Crisis intervention for people with severe mental illnesses.
AB  - BACKGROUND: A particularly difficult challenge for community treatment of people
      with serious mental illnesses is the delivery of an acceptable level of care
      during the acute phases of severe mental illness. Crisis intervention models of
      care were developed as a possible solution. OBJECTIVES: To review the effects of
      crisis intervention models for anyone with serious mental illness experiencing an
      acute episode, compared with 'standard care'. SEARCH METHODS: We updated the
      1998, 2003 and 2006 searches with a search of the Cochrane Schizophrenia Group's
      Register of trials (2010) which is based on regular searches of CINAHL, EMBASE,
      MEDLINE, and PsycINFO. SELECTION CRITERIA: We included all randomised controlled
      trials of crisis intervention models versus standard care for people with severe
      mental illnesses. DATA COLLECTION AND ANALYSIS: We independently extracted data
      from these trials and we estimated risk ratios (RR) or mean differences (MD),
      with 95% confidence intervals (CI). We assumed that people who left early from a
      trial had no improvement. MAIN RESULTS: Three new studies have been found since
      the last review in 2006 to add to the five studies already included in this
      review. None of the previously included studies investigated crisis intervention
      alone; all used a form of home care for acutely ill people, which included
      elements of crisis intervention. However, one of the new studies focuses purely
      on crisis intervention as provided by Crisis Resolution Home Teams within the UK;
      the two other new studies investigated crisis houses i.e. residential
      alternatives to hospitalisation providing home-like environments.Crisis
      intervention appears to reduce repeat admissions to hospital after the initial
      'index' crises investigated in the included studies, this was particularly so for
      mobile crisis teams supporting patients in their own homes.Crisis intervention
      reduces the number of people leaving the study early, reduces family burden, is a
      more satisfactory form of care for both patients and families and at three months
      after crisis, mental state is superior to standard care. We found no differences
      in death outcomes. Some studies found crisis interventions to be more cost
      effective than hospital care but all numerical data were either skewed or
      unusable. No data on staff satisfaction, carer input, complications with
      medication or number of relapses were available. AUTHORS' CONCLUSIONS: Care based
      on crisis intervention principles, with or without an ongoing home care package,
      appears to be a viable and acceptable way of treating people with serious mental
      illnesses. If this approach is to be widely implemented it would seem that more
      evaluative studies are still needed.

PMID- 22592674
TI  - Physical training for asthma.
AB  - BACKGROUND: People with asthma may show less tolerance to exercise due to
      worsening asthma symptoms during exercise or other reasons such as
      deconditioning, as a consequence of inactivity. Some may also restrict activities
      as per medical advice or family influence and this might result in reduced
      physical fitness. Physical training programs aim to improve physical fitness,
      neuromuscular coordination and self confidence. Subjectively, many people with
      asthma report that they are symptomatically better when fit, but results from
      trials have varied and have been difficult to compare because of different
      designs and training protocols. Also, as exercise can induce asthma, the safety
      of exercise programmes need to be considered. OBJECTIVES: To gain a better
      understanding of the effect of physical training on the respiratory and general
      health of people with asthma, from randomised trials. SEARCH METHODS: We searched
      the Cochrane Airways Group Specialised Register of trials up to April 2011.
      SELECTION CRITERIA: We included randomised trials of people over eight years of
      age with asthma who were randomised to undertake physical training. Physical
      training had to be undertaken for at least twenty minutes, two times a week, over
      a minimum period of four weeks. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed eligibility for inclusion and the quality of trials. MAIN
      RESULTS: Nineteen studies (695 participants) were included in this review.
      Physical training was well tolerated with no adverse effects reported. None of
      the studies mentioned worsening of asthma symptoms following physical training.
      Physical training improved cardiopulmonary fitness as measured by a statistically
      and clinically significant increase in maximum oxygen uptake (MD 5.57 mL/kg/min;
      95% confidence interval (CI) 4.36 to 6.78; six studies on 149 participants) and
      maximum expiratory ventilation (6.0 L/min, 95% CI 1.57 to 10.43; four studies on
      111 participants) with no significant effect on resting lung function (performed
      in four studies). Although there were insufficient data to pool due to diverse
      reporting tools, there is some evidence available to suggest that physical
      training may have positive effects on health-related quality of life, with four
      of five studies producing a statistically and clinically significant benefit.
      AUTHORS' CONCLUSIONS: This review demonstrated that physical training can improve
      cardiopulmonary fitness and was well tolerated among people with asthma in the
      included studies. As such, people with stable asthma should be encouraged to
      partake in regular exercise training, without fear of symptom exacerbation.

PMID- 22592677
TI  - Tiagabine add-on for drug-resistant partial epilepsy.
AB  - BACKGROUND: Epilepsy is a common neurological condition, affecting almost 0.5 to
      1% of the population. Nearly 30% of people with epilepsy are resistant to
      currently available drugs. Tiagabine is one of the newer antiepileptic drugs and
      its effects as an adjunct (add-on) to standard drugs are assessed in this review.
      OBJECTIVES: To evaluate the effects of add-on treatment with tiagabine upon
      seizures, adverse effects, cognition and quality of life for people with drug
      resistant localisation related seizures. SEARCH METHODS: This is an updated
      version of the original Cochrane review published in issue 10, 2010. We searched
      the Cochrane Epilepsy Group's Specialised Register (December 2011), the Cochrane
      Central Register of Controlled Trials (CENTRAL, issue 4, 2011 of The Cochrane
      Library), and MEDLINE (1948 to November 2011). No language restrictions were
      imposed. We also contacted the manufacturers of tiagabine and experts in the
      field to seek any ongoing or unpublished studies. SELECTION CRITERIA: Randomised
      placebo controlled add-on trials of people of any age with localisation related
      seizures, in which an adequate method of concealment of randomisation was used
      were included. The studies could be double, single or unblinded and be of
      parallel or crossover design. They had to have a minimum treatment period of
      eight weeks. Trials using an active drug control group were also included. DATA
      COLLECTION AND ANALYSIS: Two review authors independently selected trials for
      inclusion and extracted data. Any disagreements were resolved by discussion.
      Outcomes investigated included 50% or greater reduction in seizure frequency;
      treatment withdrawal; adverse effects; effects on cognition and quality of life.
      The primary analyses were by intention-to-treat. Worst case and best case
      analyses were also calculated for seizure outcomes. Dose response was evaluated
      in regression models. MAIN RESULTS: Four parallel group and two crossover group
      trials were included. The overall relative risk (RR) with 95% confidence
      intervals (CIs) for a 50% or greater reduction in seizure frequency (tiagabine
      versus placebo) was 3.16 (95% CI 1.97 to 5.07). Due to differences in response
      rates among trials, regression models were unable to provide reliable estimates
      of responses to individual doses. The RR for treatment withdrawal was 1.81 (95%
      CI 1.25 to 2.62). The 99% CIs for the following adverse effects: dizziness;
      fatigue; nervousness and tremor did not include unity, indicating that they are
      significantly associated with tiagabine. For cognitive and quality of life
      outcomes the limited data available suggested that there were no significant
      effects on cognition and mood and adjustment. AUTHORS' CONCLUSIONS: Tiagabine
      reduces seizure frequency but is associated with some adverse effects when used
      as an add-on for people with drug-resistant localisation-related seizures.

PMID- 22592676
TI  - Interventions for smoking cessation in hospitalised patients.
AB  - BACKGROUND: Smoking contributes to reasons for hospitalisation, and the period of
      hospitalisation may be a good time to provide help with quitting. OBJECTIVES: To
      determine the effectiveness of interventions for smoking cessation that are
      initiated for hospitalised patients. SEARCH METHODS: We searched the Cochrane
      Tobacco Addiction Group register which includes papers identified from CENTRAL,
      MEDLINE, EMBASE and PsycINFO in December 2011 for studies of interventions for
      smoking cessation in hospitalised patients, using terms including (hospital and
      patient*) or hospitali* or inpatient* or admission* or admitted. SELECTION
      CRITERIA: Randomized and quasi-randomized trials of behavioural, pharmacological
      or multicomponent interventions to help patients stop smoking, conducted with
      hospitalised patients who were current smokers or recent quitters (defined as
      having quit more than one month before hospital admission). The intervention had
      to start in the hospital but could continue after hospital discharge. We excluded
      studies of patients admitted to facilities that primarily treat psychiatric
      disorders or substance abuse, studies that did not report abstinence rates and
      studies with follow-up of less than six months. Both acute care hospitals and
      rehabilitation hospitals were included in this update, with separate analyses
      done for each type of hospital. DATA COLLECTION AND ANALYSIS: Two authors
      extracted data independently for each paper, with disagreements resolved by
      consensus. MAIN RESULTS: Fifty trials met the inclusion criteria. Intensive
      counselling interventions that began during the hospital stay and continued with
      supportive contacts for at least one month after discharge increased smoking
      cessation rates after discharge (risk ratio (RR) 1.37, 95% confidence interval
      (CI) 1.27 to 1.48; 25 trials). A specific benefit for post-discharge contact
      compared with usual care was found in a subset of trials in which all
      participants received a counselling intervention in the hospital and were
      randomly assigned to post-discharge contact or usual care. No statistically
      significant benefit was found for less intensive counselling interventions.
      Adding nicotine replacement therapy (NRT) to an intensive counselling
      intervention increased smoking cessation rates compared with intensive
      counselling alone (RR 1.54, 95% CI 1.34 to 1.79, six trials). Adding varenicline
      to intensive counselling had a non-significant effect in two trials (RR 1.28, 95%
      CI 0.95 to 1.74). Adding bupropion did not produce a statistically significant
      increase in cessation over intensive counselling alone (RR 1.04, 95% CI 0.75 to
      1.45, three trials). A similar pattern of results was observed in a subgroup of
      smokers admitted to hospital because of cardiovascular disease (CVD). In this
      subgroup, intensive intervention with follow-up support increased the rate of
      smoking cessation (RR 1.42, 95% CI 1.29 to 1.56), but less intensive
      interventions did not. One trial of intensive intervention including counselling
      and pharmacotherapy for smokers admitted with CVD assessed clinical and health
      care utilization endpoints, and found significant reductions in all-cause
      mortality and hospital readmission rates over a two-year follow-up period. These
      trials were all conducted in acute care hospitals. A comparable increase in
      smoking cessation rates was observed in a separate pooled analysis of intensive
      counselling interventions in rehabilitation hospitals (RR 1.71, 95% CI 1.37 to
      2.14, three trials). AUTHORS' CONCLUSIONS: High intensity behavioural
      interventions that begin during a hospital stay and include at least one month of
      supportive contact after discharge promote smoking cessation among hospitalised
      patients. The effect of these interventions was independent of the patient's
      admitting diagnosis and was found in rehabilitation settings as well as acute
      care hospitals. There was no evidence of effect for interventions of lower
      intensity or shorter duration. This update found that adding NRT to intensive
      counselling significantly increases cessation rates over counselling alone. There
      is insufficient direct evidence to conclude that adding bupropion or varenicline
      to intensive counselling increases cessation rates over what is achieved by
      counselling alone.

PMID- 22592675
TI  - Support for healthy breastfeeding mothers with healthy term babies.
AB  - BACKGROUND: There is extensive evidence of important health risks for infants and
      mothers related to not breastfeeding. In 2003, the World Health Organization
      recommended infants be exclusively breastfed until six months of age, with
      breastfeeding continuing as an important part of the infant's diet till at least
      two years of age. However, breastfeeding rates in many countries currently do not
      reflect this recommendation. OBJECTIVES: To assess the effectiveness of support
      for breastfeeding mothers. SEARCH METHODS: We searched the Cochrane Pregnancy and
      Childbirth Group's Trials Register (3 October 2011). SELECTION CRITERIA:
      Randomised or quasi-randomised controlled trials comparing extra support for
      healthy breastfeeding mothers of healthy term babies with usual maternity care.
      DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial
      quality and extracted data. MAIN RESULTS: Of the 67 studies that we assessed as
      eligible for inclusion, 52 contributed outcome data to the review (56,451 mother
      infant pairs) from 21 countries. All forms of extra support analysed together
      showed an increase in duration of 'any breastfeeding' (includes partial and
      exclusive breastfeeding) (risk ratio (RR) for stopping any breastfeeding before
      six months 0.91, 95% confidence interval (CI) 0.88 to 0.96). All forms of extra
      support together also had a positive effect on duration of exclusive
      breastfeeding (RR at six months 0.86, 95% CI 0.82 to 0.91; RR at four to six
      weeks 0.74, 95% CI 0.61 to 0.89). Extra support by both lay and professionals had
      a positive impact on breastfeeding outcomes. Maternal satisfaction was poorly
      reported. AUTHORS' CONCLUSIONS: All women should be offered support to breastfeed
      their babies to increase the duration and exclusivity of breastfeeding. Support
      is likely to be more effective in settings with high initiation rates, so efforts
      to increase the uptake of breastfeeding should be in place. Support may be
      offered either by professional or lay/peer supporters, or a combination of both.
      Strategies that rely mainly on face-to-face support are more likely to succeed.
      Support that is only offered reactively, in which women are expected to initiate
      the contact, is unlikely to be effective; women should be offered ongoing visits
      on a scheduled basis so they can predict that support will be available. Support
      should be tailored to the needs of the setting and the population group.

PMID- 22592678
TI  - Calcium antagonists for acute ischemic stroke.
AB  - BACKGROUND: The sudden loss of blood supply in ischemic stroke is associated with
      the increase of calcium ions within neurons. Inhibiting this increase could
      protect neurons and hence might reduce neurological impairment, disability and
      handicap after stroke. OBJECTIVES: To determine whether calcium antagonists
      reduce the risk of death or dependency after acute ischemic stroke. To
      investigate the influence of different drugs, dosages, routes of administration,
      time intervals after stroke and trial design on the risk of a primary outcome.
      SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (January
      2012), MEDLINE (1950 to December 2011), EMBASE (1980 to December 2011), the
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library,
      2011 issue 4) and four Chinese databases (December 2011): Chinese Biological
      Medicine Database (CBM-disc), China National Knowledge Infrastructure (CNKI),
      Chinese scientific periodical database of VIP information and Wanfang Data. We
      also contacted trialists and researchers. SELECTION CRITERIA: All truly
      randomized trials comparing a calcium antagonist with control in patients with
      acute ischemic stroke. DATA COLLECTION AND ANALYSIS: Two authors assessed all
      trials and extracted the data. We used death or dependency at the end of long
      term follow-up (at least three months) in activities of daily living as the
      primary outcome. Analyses were, if possible, intention-to-treat. MAIN RESULTS: We
      included 34 trials including 7731 patients. There was no effect of calcium
      antagonists on the primary outcome (risk ratio (RR) 1.05; 95% confidence interval
      (CI) 0.98 to 1.13), or on death at the end of follow-up (RR 1.07, 95% CI 0.98 to
      1.17). Comparisons of different doses of nimodipine suggested that the highest
      doses were associated with poorer outcome. AUTHORS' CONCLUSIONS: No evidence is
      available using calcium antagonists in patients with acute ischemic stroke is
      effective.

PMID- 22592679
TI  - Cognitive-behavioural interventions for children who have been sexually abused.
AB  - BACKGROUND: Despite differences in how it is defined, there is a general
      consensus amongst clinicians and researchers that the sexual abuse of children
      and adolescents ('child sexual abuse') is a substantial social problem worldwide.
      The effects of sexual abuse manifest in a wide range of symptoms, including fear,
      anxiety, post-traumatic stress disorder and various externalising and
      internalising behaviour problems, such as inappropriate sexual behaviours. Child
      sexual abuse is associated with increased risk of psychological problems in
      adulthood. Cognitive-behavioural approaches are used to help children and their
      non-offending or 'safe' parent to manage the sequelae of childhood sexual abuse.
      This review updates the first Cochrane review of cognitive-behavioural approaches
      interventions for children who have been sexually abused, which was first
      published in 2006. OBJECTIVES: To assess the efficacy of cognitive-behavioural
      approaches (CBT) in addressing the immediate and longer-term sequelae of sexual
      abuse on children and young people up to 18 years of age. SEARCH METHODS: We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2011 Issue
      4); MEDLINE (1950 to November Week 3 2011); EMBASE (1980 to Week 47 2011); CINAHL
      (1937 to 2 December 2011); PsycINFO (1887 to November Week 5 2011); LILACS (1982
      to 2 December 2011) and OpenGrey, previously OpenSIGLE (1980 to 2 December 2011).
      For this update we also searched ClinicalTrials.gov and the International
      Clinical Trials Registry Platform (ICTRP). SELECTION CRITERIA: We included
      randomised or quasi-randomised controlled trials of CBT used with children and
      adolescents up to age 18 years who had experienced being sexually abused,
      compared with treatment as usual, with or without placebo control. DATA
      COLLECTION AND ANALYSIS: At least two review authors independently assessed the
      eligibility of titles and abstracts identified in the search. Two review authors
      independently extracted data from included studies and entered these into Review
      Manager 5 software. We synthesised and presented data in both written and
      graphical form (forest plots). MAIN RESULTS: We included 10 trials, involving 847
      participants. All studies examined CBT programmes provided to children or
      children and a non-offending parent. Control groups included wait list controls
      (n = 1) or treatment as usual (n = 9). Treatment as usual was, for the most part,
      supportive, unstructured psychotherapy. Generally the reporting of studies was
      poor. Only four studies were judged 'low risk of bias' with regards to sequence
      generation and only one study was judged 'low risk of bias' in relation to
      allocation concealment. All studies were judged 'high risk of bias' in relation
      to the blinding of outcome assessors or personnel; most studies did not report on
      these, or other issues of bias. Most studies reported results for study
      completers rather than for those recruited.Depression, post-traumatic stress
      disorder (PTSD), anxiety and child behaviour problems were the primary outcomes.
      Data suggest that CBT may have a positive impact on the sequelae of child sexual
      abuse, but most results were not statistically significant. Strongest evidence
      for positive effects of CBT appears to be in reducing PTSD and anxiety symptoms,
      but even in these areas effects tend to be 'moderate' at best. Meta-analysis of
      data from five studies suggested an average decrease of 1.9 points on the Child
      Depression Inventory immediately after intervention (95% confidence interval (CI)
      decrease of 4.0 to increase of 0.4; I(2) = 53%; P value for heterogeneity =
      0.08), representing a small to moderate effect size. Data from six studies
      yielded an average decrease of 0.44 standard deviations on a variety of child
      post-traumatic stress disorder scales (95% CI 0.16 to 0.73; I(2) = 46%; P value
      for heterogeneity = 0.10). Combined data from five studies yielded an average
      decrease of 0.23 standard deviations on various child anxiety scales (95% CI 0.3
      to 0.4; I(2) = 0%; P value for heterogeneity = 0.84). No study reported adverse
      effects. AUTHORS' CONCLUSIONS: The conclusions of this updated review remain the
      same as those when it was first published. The review confirms the potential of
      CBT to address the adverse consequences of child sexual abuse, but highlights the
      limitations of the evidence base and the need for more carefully conducted and
      better reported trials.

PMID- 22592680
TI  - Early administration of inhaled corticosteroids for preventing chronic lung
      disease in ventilated very low birth weight preterm neonates.
AB  - BACKGROUND: Chronic lung disease remains a common complication among preterm
      infants. There is increasing evidence that inflammation plays an important role
      in the pathogenesis of CLD. Due to their strong anti-inflammatory properties,
      corticosteroids are an attractive intervention strategy. However, there are
      growing concerns regarding short and long-term effects of systemic
      corticosteroids. Theoretically, administration of inhaled corticosteroids may
      allow for beneficial effects on the pulmonary system with a lower risk of
      undesirable systemic side effects. OBJECTIVES: To determine the impact of inhaled
      corticosteroids administered to ventilated very low birth weight preterm neonates
      in the first two weeks of life for the prevention of chronic lung disease (CLD).
      SEARCH METHODS: Randomised and quasi-randomised trials were identified by
      searching the Cochrane Central Register of Controlled Trials (CENTRAL, The
      Cochrane Library, Issue 3, 2007), MEDLINE (1966 to July 2007), EMBASE (1980 to
      July 2007), CINAHL (1982 to July 2007), reference lists of published trials and
      abstracts published in Pediatric Research or electronically on the Pediatric
      Academic Societies web-site (1990 to April 2007).This search was updated in 2011.
      SELECTION CRITERIA: Randomised controlled trials of inhaled corticosteroid
      therapy initiated within the first two weeks of life in ventilated preterm
      infants with birth weight <1500 grams were included in this review. DATA
      COLLECTION AND ANALYSIS: Data regarding clinical outcomes including chronic lung
      disease at 28 days or 36 weeks postmenstrual age (PMA), mortality, combined
      outcome of death or CLD at 28 days of age and at 36 weeks PMA, the need for
      systemic corticosteroids, failure to extubate within 14 days and adverse effects
      of corticosteroids were evaluated. All data were analysed using RevMan 4.2.10.
      When possible, meta-analysis was performed using relative risk (RR), risk
      difference (RD), along with their 95% confidence intervals (CI). If RD was
      significant, the number needed to treat (NNT) was calculated. MAIN RESULTS: One
      ongoing trial was identified for inclusion in this update. Eleven trials
      assessing the impact of inhaled corticosteroid for the prevention of CLD were
      identified. Four trials were excluded. The present review includes data analyses
      based on seven qualifying trials. There was no statistically significant effect
      of inhaled steroids on CLD either at 28 days [typical RR 1.05 (95% CI 0.84 to
      1.32); typical RD 0.02 (95% CO -0.07 to 0.11)] or at 36 weeks PMA [typical RR
      0.97 (95% CI 0.62 to 1.52); typical RD 0.00 (95% CI -0.07, 0.06)], when analysed
      either for all randomised infants or among survivors. No statistically
      significant differences were noted for mortality or for the combined outcome of
      mortality and CLD either at 28 days of age or at 36 weeks PMA. There were no
      statistically significant differences in adverse events between groups. AUTHORS'
      CONCLUSIONS: Based on this updated review, there is no evidence from the trials
      reviewed that early administration (in the first two weeks of life) of inhaled
      steroids to ventilated preterm neonates was effective in reducing the incidence
      of CLD. Currently, use of inhaled steroids in this population cannot be
      recommended. Studies are needed to identify the risk/benefit ratio of different
      delivery techniques and dosing schedules for the administration of these
      medications. Studies need to address both the short-term and long-term benefits
      and adverse effects of inhaled steroids with particular attention to
      neurodevelopmental outcome.

PMID- 22592681
TI  - Position in the second stage of labour for women without epidural anaesthesia.
AB  - BACKGROUND: For centuries, there has been controversy around whether being
      upright (sitting, birthing stools, chairs, squatting, kneeling) or lying down
      have advantages for women delivering their babies. OBJECTIVES: To assess the
      benefits and risks of the use of different positions during the second stage of
      labour (i.e. from full dilatation of the uterine cervix). SEARCH METHODS: We
      searched the Cochrane Pregnancy and Childbirth Group Trials Register (28 February
      2012). SELECTION CRITERIA: Randomised or quasi-randomised controlled trials of
      any upright or lateral position assumed by pregnant women during the second stage
      of labour compared with supine or lithotomy positions. Secondary comparisons
      include comparison of different upright positions and the lateral position. DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed trials for
      inclusion and assessed trial quality. At least two review authors extracted the
      data. Data were checked for accuracy. MAIN RESULTS: Results should be interpreted
      with caution as the methodological quality of the 22 included trials (7280 women)
      was variable.In all women studied (primigravid and multigravid) there was a non
      significant reduction in duration of second stage in the upright group (mean
      difference (MD) -3.71 minutes; 95% confidence interval (CI) -8.78 to 1.37
      minutes; 10 trials, 3485 women; random-effects, I(2) = 94%), a significant
      reduction in assisted deliveries (risk ratio (RR) 0.78; 95% CI 0.68 to 0.90; 19
      trials, 6024 women, I(2)= 27%), a reduction in episiotomies (average RR 0.79, 95%
      CI 0.70 to 0.90, 12 trials, 4541 women; random-effects, I(2) = 7%), an increase
      in second degree perineal tears (RR 1.35; 95% CI 1.20 to 1.51, 14 trials, 5367
      women), increased estimated blood loss greater than 500 ml (RR 1.65; 95% CI 1.32
      to 2.60; 13 trials, 5158 women, asymmetric funnel plot indicating publication
      bias), fewer abnormal fetal heart rate patterns (RR 0.46; 95% CI 0.22 to 0.93;
      two trials, 617 women). In primigravid women the use of any upright compared with
      supine positions was associated with: non-significant reduction in duration of
      second stage of labour (nine trials: mean 3.24 minutes, 95% CI 1.53 to 4.95
      minutes) - this reduction was largely due to women allocated to the use of the
      birth cushion. AUTHORS' CONCLUSIONS: The findings of this review suggest several
      possible benefits for upright posture in women without epidural, but with the
      possibility of increased risk of blood loss greater than 500 mL. Until such time
      as the benefits and risks of various delivery positions are estimated with
      greater certainty, when methodologically stringent data from trials are
      available, women should be allowed to make choices about the birth positions in
      which they might wish to assume for birth of their babies.

PMID- 22592682
TI  - Inhaled versus systemic corticosteroids for the treatment of chronic lung disease
      in ventilated very low birth weight preterm infants.
AB  - BACKGROUND: Chronic lung disease (CLD) remains a serious and common problem among
      very low birth weight (VLBW) infants despite the use of antenatal steroids and
      postnatal surfactant therapy to decrease the incidence and severity of
      respiratory distress syndrome. Due to their anti-inflammatory properties,
      corticosteroids have been widely used to treat or prevent CLD. However, the use
      of systemic steroids has been associated with serious short and long-term adverse
      effects. Administration of corticosteroids topically through the respiratory
      tract might result in beneficial effects on the pulmonary system with fewer
      undesirable systemic side effects. OBJECTIVES: To determine the effect of inhaled
      versus systemic corticosteroids administered to ventilator dependent preterm
      neonates with birth weight < 1500 g or gestational age < 32 weeks after two weeks
      of life for the treatment of evolving CLD. SEARCH METHODS: Randomised and quasi
      randomised trials were identified by searching the Cochrane Central Register of
      Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2007), MEDLINE (1966
      to June 2007), EMBASE (1980 to June 2007), CINAHL (1982 to June 2007), reference
      lists of published trials and abstracts published in Pediatric Research or
      electronically on the Pediatric Academic Societies web site (1990 to April 2007).
      This search was updated in June 2011 and included additional searches of
      Clinicaltrials.gov, Controlled-trials.com and Web of Science. SELECTION CRITERIA:
      Randomised or quasi-randomised trials comparing inhaled versus systemic
      corticosteroid therapy (irrespective of the dose and duration of therapy)
      starting after the first two weeks of life in ventilator dependent VLBW infants.
      DATA COLLECTION AND ANALYSIS: Data were extracted regarding clinical outcomes and
      were analysed using Review Manager. When appropriate, meta-analysis was performed
      using relative risk (RR), risk difference (RD), and weighted mean difference
      (WMD) along with their 95% confidence intervals (CI). If RD was statistically
      significant, the number needed to benefit (NNTB) or the number needed to harm
      (NNTH) was calculated. MAIN RESULTS: Five trials comparing inhaled versus
      systemic corticosteroids in the treatment of CLD were identified. Two trials were
      excluded as both included non-ventilator dependent patients and three trials
      qualified for inclusion in this review. No new trials were identified in the 2011
      update.Halliday et al (Halliday 2001) randomised infants at < 72 hours (n = 292),
      while Rozycki et al (Rozycki 2003) and Suchomski et al (Suchomski 2002)
      randomised at 12 to 21 days. The data from the two trials of Rozycki et al and
      Suchmoski et al are combined using meta-analytic techniques. The data from the
      trial by Halliday et al are reported separately, as outcomes were measured over
      different time periods from the age at randomisation.In none of the trials was
      there a statistically significant difference between the groups in the incidence
      of CLD at 36 weeks PMA among all randomised infants. The estimates for the trial
      by Halliday et al (Halliday 2001) were RR 1.10 (95% CI 0.82 to 1.47), RD 0.03
      (95% CI -0.08 to 0.15).For the trials by Rozycki et al (Rozycki 2003) and
      Suchomski et al (Suchomski 2002) the typical RR was 1.02 (95% CI 0.83 to 1.25)
      and the typical RD 0.01 (95% CI -0.11 to 0.14); (number of infants = 139 ). There
      were no statistically significant differences between the groups in either trial
      for oxygen dependency at 28 days of age, death by 28 days or 36 weeks PMA, the
      combined outcome of death by or CLD at 28 days or 36 weeks PMA, duration of
      intubation, duration of oxygen dependence, or adverse effects. Information on the
      long-term neurodevelopmental outcomes was not available. AUTHORS' CONCLUSIONS:
      This review found no evidence that inhaled corticosteroids confer net advantages
      over systemic corticosteroids in the management of ventilator dependent preterm
      infants. Neither inhaled steroids nor systemic steroids can be recommended as
      standard treatment for ventilated preterm infants. There was no evidence of
      difference in effectiveness or side-effect profiles for inhaled versus systemic
      steroids. A better delivery system guaranteeing selective delivery of inhaled
      steroids to the alveoli might result in beneficial clinical effects without
      increasing side-effects. To resolve this issue, studies are needed to identify
      the risk/benefit ratio of different delivery techniques and dosing schedules for
      the administration of these medications. The long-term effects of inhaled
      steroids, with particular attention to neurodevelopmental outcome, should be
      addressed in future studies.

PMID- 22592683
TI  - Inhaled versus systemic corticosteroids for preventing chronic lung disease in
      ventilated very low birth weight preterm neonates.
AB  - BACKGROUND: Chronic lung disease (CLD) remains an important cause of mortality
      and morbidity in preterm infants and inflammation plays an important role in its
      pathogenesis. The use of inhaled corticosteroids may modulate the inflammatory
      process without concomitant high systemic steroid concentrations and less risk of
      adverse effects. OBJECTIVES: To determine the effect of inhaled versus systemic
      corticosteroids started within the first two weeks of life on preventing CLD in
      ventilated very low birth weight (VLBW) infants. SEARCH METHODS: Randomised and
      quasi-randomised trials were identified by searching The Cochrane Library,
      MEDLINE , EMBASE , CINAHL, reference lists of published trials and abstracts
      published in Pediatric Research or electronically on the Pediatric Academic
      Societies web site in June 2007.This search was updated in June 2011 and included
      additional searches of Clinicaltrials.gov, Controlled-trials.com and Web of
      Science. SELECTION CRITERIA: Randomised or quasi-randomised clinical trials
      comparing inhaled versus systemic corticosteroid therapy (regardless of the dose
      and duration of therapy) started in the first two weeks of life in VLBW infants
      receiving assisted ventilation. DATA COLLECTION AND ANALYSIS: Outcomes including
      CLD at 28 days or 36 weeks postmenstrual age (PMA), mortality, the combined
      outcome of death or CLD at 28 days or 36 weeks PMA, other pulmonary outcomes and
      adverse effects were evaluated. All data were analysed using RevMan 5.1. Meta
      analyses were performed using relative risk (RR), risk difference (RD), and mean
      difference (MD) with their 95% confidence intervals (CI). If RD was significant,
      the numbers needed to benefit (NNTB) or to harm (NNTH) were calculated. MAIN
      RESULTS: No new trials were identified in this update. Two trials qualified for
      inclusion in this review. The incidence of CLD at 36 weeks PMA was increased (of
      borderline statistical significance) in the inhaled steroid group [RR 1.45 (95%
      CI 0.99 to 2.11); RD 0.11 (95% CI 0.00 to 0.21), p = 0.05, one trial, n = 278].
      The incidence of CLD at 36 weeks PMA among all survivors [RR 1.34 (95% CI 0.94 to
      1.90); RD 0.11 (95% CI -0.02 to 0.24), one trial, n = 206], oxygen dependency at
      28 days (two trials, n = 294), death by 28 days (two trials, n = 294) or 36 weeks
      PMA (two trials, n = 294) and the combined outcome of death or CLD by 28 days
      (two trials, n = 294) or 36 weeks PMA (one trial, n = 278) did not differ
      significantly between the groups. The duration of mechanical ventilation was
      significantly longer in the inhaled steroid group as compared to the systemic
      steroid group [typical MD 4 days (95% CI 0.2 to 8); two trials, n = 294] as was
      the duration of supplemental oxygen [typical MD 11 days (95% CI 2 to 20); two
      trials, n = 294]. The incidence of hyperglycaemia was significantly lower in the
      group receiving inhaled steroids [RR 0.52 (95% CI 0.39 to 0.71); RD -0.25 (95% CI
      -0.37 to -0.14); one trial, n = 278; NNTB 4 (95% CI 3 to 7) to avoid one infant
      experiencing hyperglycaemia]. The rate of patent ductus arteriosus was increased
      in the group receiving inhaled steroids [RR 1.64 (95% CI 1.23 to 2.17); RD 0.21
      (95% CI 0.10 to 0.33); one trial, n = 278; NNTH 5 (95% CI 3 to 10)]. No
      information was available on long-term neurodevelopmental outcomes. AUTHORS'
      CONCLUSIONS: This review found no evidence that early inhaled steroids confer
      important advantages over systemic steroids in the management of ventilator
      dependent preterm infants. Neither inhaled steroids nor systemic steroids can be
      recommended as a part of standard practice for ventilated preterm infants.
      Because they might have fewer adverse effects than systemic steroids, further
      randomised controlled trials of inhaled steroids are needed that address
      risk/benefit ratio of different delivery techniques, dosing schedules and long
      term effects, with particular attention to neurodevelopmental outcome.

PMID- 22592684
TI  - Reduced or modified dietary fat for preventing cardiovascular disease.
AB  - BACKGROUND: Reduction and modification of dietary fats have differing effects on
      cardiovascular risk factors (such as serum cholesterol), but their effects on
      important health outcomes are less clear. OBJECTIVES: To assess the effect of
      reduction and/or modification of dietary fats on mortality, cardiovascular
      mortality, cardiovascular morbidity and individual outcomes including myocardial
      infarction, stroke and cancer diagnoses in randomised clinical trials of at least
      6 months duration. SEARCH METHODS: For this review update, the Cochrane Central
      Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, were searched
      through to June 2010. References of Included studies and reviews were also
      checked. SELECTION CRITERIA: Trials fulfilled the following criteria: 1)
      randomised with appropriate control group, 2) intention to reduce or modify fat
      or cholesterol intake (excluding exclusively omega-3 fat interventions), 3) not
      multi factorial, 4) adult humans with or without cardiovascular disease, 5)
      intervention at least six months, 6) mortality or cardiovascular morbidity data
      available. DATA COLLECTION AND ANALYSIS: Participant numbers experiencing health
      outcomes in each arm were extracted independently in duplicate and random effects
      meta-analyses, meta-regression, sub-grouping, sensitivity analyses and funnel
      plots were performed. MAIN RESULTS: This updated review suggested that reducing
      saturated fat by reducing and/or modifying dietary fat reduced the risk of
      cardiovascular events by 14% (RR 0.86, 95% CI 0.77 to 0.96, 24 comparisons,
      65,508 participants of whom 7% had a cardiovascular event, I(2) 50%). Subgrouping
      suggested that this reduction in cardiovascular events was seen in studies of fat
      modification (not reduction - which related directly to the degree of effect on
      serum total and LDL cholesterol and triglycerides), of at least two years
      duration and in studies of men (not of women). There were no clear effects of
      dietary fat changes on total mortality (RR 0.98, 95% CI 0.93 to 1.04, 71,790
      participants) or cardiovascular mortality (RR 0.94, 95% CI 0.85 to 1.04, 65,978
      participants). This did not alter with sub-grouping or sensitivity analysis.Few
      studies compared reduced with modified fat diets, so direct comparison was not
      possible. AUTHORS' CONCLUSIONS: The findings are suggestive of a small but
      potentially important reduction in cardiovascular risk on modification of dietary
      fat, but not reduction of total fat, in longer trials. Lifestyle advice to all
      those at risk of cardiovascular disease and to lower risk population groups,
      should continue to include permanent reduction of dietary saturated fat and
      partial replacement by unsaturates. The ideal type of unsaturated fat is unclear.

PMID- 22592686
TI  - Immunotherapy for IgM anti-myelin-associated glycoprotein paraprotein-associated
      peripheral neuropathies.
AB  - BACKGROUND: Serum monoclonal anti-myelin-associated glycoprotein antibodies may
      be pathogenic in some people with immunoglobulin M (IgM) paraprotein and
      demyelinating neuropathy. Immunotherapies aimed at reducing the level of these
      antibodies might be expected to be beneficial. This is an update of a review
      first published in 2003 and previously updated in 2006. OBJECTIVES: To assess the
      effects of immunotherapy for IgM anti-myelin-associated glycoprotein paraprotein
      associated demyelinating peripheral neuropathy. SEARCH METHODS: We searched the
      Cochrane Neuromuscular Disease Group Specialized Register 6 June 2011), CENTRAL
      (2011, Issue 2), MEDLINE (January 1966 to May 2011) and EMBASE (January 1980 to
      May 2011) for controlled trials. We also checked bibliographies and contacted
      authors and experts in the field. SELECTION CRITERIA: We included randomised or
      quasi-randomised controlled trials involving participants of any age treated with
      any type of immunotherapy for anti-myelin-associated glycoprotein antibody
      associated demyelinating peripheral neuropathy with monoclonal gammopathy of
      undetermined significance and of any severity.Our primary outcome measure was
      change in the Neuropathy Impairment Scale or Modified Rankin Scale at six months
      after randomisation. Secondary outcome measures were: Neuropathy Impairment Scale
      or the Modified Rankin Score at 12 months after randomisation; 10-metre walk
      time, subjective clinical scores and electrophysiological parameters at six and
      12 months after randomisation; IgM paraprotein levels and anti-myelin-associated
      glycoprotein antibody titres at six months after randomisation; and adverse
      effects of treatments. DATA COLLECTION AND ANALYSIS: The two authors
      independently selected studies. Two authors independently assessed the risk of
      bias in included studies. MAIN RESULTS: We identified seven eligible trials (182
      participants), which tested intravenous immunoglobulin, alfa interferon alfa-2a,
      plasma exchange, cyclophosphamide and steroids, and rituximab. Only two trials,
      of intravenous immunoglobulin (with 33 participants, including 20 with antibodies
      against myelin-associated glycoprotein), had comparable interventions and
      outcomes, but both were short-term trials.There were no clinical or statistically
      significant benefits of the treatments used on the outcomes predefined for this
      review, but not all the predefined outcomes were used in every included trial.
      Intravenous immunoglobulin showed a statistical benefit in terms of improvement
      in Modified Rankin Scale at two weeks and 10-metre walk time at four weeks.
      Cyclophosphamide failed to show any benefit in the trial's primary outcome, and
      showed a barely significant benefit in the primary outcome specified here, but
      some toxic adverse events were identified. A trial of rituximab was of poor
      methodological quality with a high risk of bias and a further larger study is
      awaited. Serious adverse events were few in the other trials. AUTHORS'
      CONCLUSIONS: There is inadequate reliable evidence from trials of immunotherapies
      in anti-myelin-associated glycoprotein paraproteinaemic neuropathy to form an
      evidence base supporting any particular immunotherapy treatment. There is very
      low quality evidence of benefit from rituximab. Large well designed randomised
      trials of at least six to 12 months duration are required to assess existing or
      novel therapies, preferably employing unified, consistent, well designed,
      responsive and valid outcome measures.

PMID- 22592687
TI  - Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro
      inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and
      subfertility.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is characterised by infrequent or
      absent ovulation (anovulation), high levels of male hormones (hyperandrogenaemia)
      and high levels of insulin (hyperinsulinaemia secondary to increased insulin
      resistance). Hyperinsulinaemia is associated with an increase in cardiovascular
      risk and the development of diabetes mellitus. Insulin-sensitising agents such as
      metformin may be effective in treating the features of PCOS, including
      anovulation. OBJECTIVES: To assess the effectiveness of insulin-sensitising drugs
      in improving reproductive outcomes and metabolic parameters for women with PCOS.
      SEARCH METHODS: We searched the Cochrane Menstrual Disorders and Subfertility
      Group Trials Register (October 2011), the Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library, 3rd Quarter 2011), CINAHL (October 2011),
      MEDLINE (January 1966 to October 2011), and EMBASE (January 1985 to October
      2011). SELECTION CRITERIA: Randomised controlled trials of insulin sensitising
      drugs compared with either placebo, no treatment, or an ovulation induction agent
      for women with PCOS, menstrual disturbance and subfertility. DATA COLLECTION AND
      ANALYSIS: Two review authors independently assessed studies for inclusion and
      trial quality, and extracted data.   MAIN RESULTS: Forty-four trials (3992 women)
      were included for analysis, 38 of them using metformin and involving 3495
      women.There was no evidence that metformin improved live birth rates, whether it
      was used alone (pooled OR 1.80, 95% CI 0.52 to 6.16, 3 trials, 115 women) or in
      combination with clomiphene (pooled OR 1.16, 95% CI 0.85 to 1.56, 7 trials, 907
      women). However, clinical pregnancy rates were improved for metformin versus
      placebo (pooled OR 2.31, 95% CI 1.52 to 3.51, 8 trials, 707 women) and for
      metformin and clomiphene versus clomiphene alone (pooled OR 1.51, 95% CI 1.17 to
      1.96, 11 trials, 1208 women). In the studies that compared metformin and
      clomiphene alone, there was evidence of an improved live birth rate (pooled OR
      0.3, 95% CI 0.17 to 0.52, 2 trials, 500 women) and clinical pregnancy rate
      (pooled OR 0.34, 95% 0.21 to 0.55, 2 trials, 500 women) in the group of obese
      women who took clomiphene.Metformin was also associated with a significantly
      higher incidence of gastrointestinal disturbances than placebo (pooled OR 4.27,
      95% CI 2.4 to 7.59, 5 trials, 318 women) but no serious adverse effects were
      reported. AUTHORS' CONCLUSIONS: In agreement with the previous review, metformin
      was associated with improved clinical pregnancy but there was no evidence that
      metformin improves live birth rates whether it is used alone or in combination
      with clomiphene, or when compared with clomiphene. Therefore, the role of
      metformin in improving reproductive outcomes in women with PCOS appears to be
      limited.

PMID- 22592688
TI  - Bisphosphonates in multiple myeloma: a network meta-analysis.
AB  - BACKGROUND: Bisphosphonates are specific inhibitors of osteoclastic activity and
      used in the treatment of patients with multiple myeloma (MM). While
      bisphosphonates are shown to be effective in reducing vertebral fractures and
      pain, their role in improving overall survival (OS) remains unclear. This is an
      update of a Cochrane review first published in 2002 and previously updated in
      2010. OBJECTIVES: To assess the evidence related to benefits and harms associated
      with use of various types of bisphosphonates (aminobisphosphonates versus
      nonamino bisphosphonates) in the management of patients with MM. Our primary
      objective was to determine whether adding bisphosphonates to standard therapy in
      MM improves OS and progression-free survival (PFS), and decreases skeletal
      related morbidity. Our secondary objectives were to determine the effects of
      bisphosphonates on pain, quality of life, incidence of hypercalcemia, incidence
      of bisphosphonate-related gastrointestinal toxicities, osteonecrosis of jaw and
      hypocalcemia. SEARCH METHODS: We searched MEDLINE, LILACS, EMBASE (December 2009
      to October 2011) and the Cochrane Controlled Trials Register (all years, latest
      Issue September 2011) to identify all randomized trials in MM up to October 2011
      using a combination of text and MeSH terms. We also handsearched relevant meeting
      proceedings (December 2009 to October 2011). SELECTION CRITERIA: Any randomized
      controlled trial (RCT) assessing the role of bisphosphonates and observational
      studies or case reports examining bisphosphonate-related osteonecrosis of the jaw
      in patients with MM were eligible for inclusion. DATA COLLECTION AND ANALYSIS:
      Two review authors extracted the data. Data were pooled and reported as hazard
      ratio (HR) or risk ratio (RR) under a random-effects model. Statistical
      heterogeneity was explored using metaregression. MAIN RESULTS: In this update, we
      included 2 studies (2464 patients) that were not part of our last Cochrane review
      published in 2010. In this review we included 16 RCTs comparing bisphosphonates
      with either placebo or no treatment and 4 RCTs with a different bisphosphonate as
      a comparator. The 20 included RCTs enrolled 6692 patients. Overall methodological
      quality of reporting was moderate. Thirty per cent (6/20) of trials reported the
      method of generating the randomization sequence. Forty per cent (8/20) of trials
      had adequate allocation concealment. Withdrawals and dropouts were described in
      60% (12/20) of trials. Pooled results showed no direct effect of bisphosphonates
      on OS compared with placebo or no treatment (HR 0.96, 95% CI 0.82 to 1.13; P =
      0.64). However, there was a statistically significant heterogeneity among the
      included RCTs (I(2) = 55%, P = 0.01) for OS. To explain this heterogeneity we
      performed a metaregression assessing the relationship between bisphosphonate
      potency and improvement in OS, which found indicating an OS benefit with
      zoledronate (P = 0.058). This provided a further rationale for performing network
      meta-analyses of the various types of bisphosphonates that were not compared head
      to head in RCTs. Results from network meta-analyses showed superior OS with
      zoledronate compared with etidronate (HR 0.43, 95% CI 0.16 to 0.86) and placebo
      (HR 0.61, 95% CI 0.28 to 0.98). However, there was no difference between
      zoledronate and other bisphosphonates. Pooled analysis did not demonstrate a
      beneficial effect of bisphosphonates compared with placebo or no treatment in
      improving PFS (HR 0.70, 95% CI 0.41 to 1.19; P = 0.18) There was no heterogeneity
      among trials reporting PFS estimates (I(2) = 35%, P = 0.20).Pooled analysis
      demonstrated a beneficial effect of bisphosphonates compared with placebo or no
      treatment on prevention of pathological vertebral fractures (RR 0.74, 95% CI 0.62
      to 0.89; I(2) = 7%), skeletal-related events (SRE) (RR 0.80, 95% CI 0.72 to 0.89;
      I(2) = 2%) and amelioration of pain (RR 0.75, 95% CI 0.60 to 0.95; I(2) = 63%).
      The network meta-analysis did not show any difference in the incidence of
      osteonecrosis of the jaw (5 RCTs, 3198 patients) between bisphosphonates. Rates
      of osteonecrosis of the jaw in observational studies (9 studies, 1400 patients)
      ranged from 0% to 51%. The pooled results (6 RCTs, 1689 patients) showed no
      statistically significant increase in frequency of gastrointestinal symptoms with
      the use of bisphosphonates compared with placebo or no treatment (RR 1.23, 95% CI
      0.95 to 1.60; P = 0.11).The pooled results (3 RCTs, 1002 patients) showed no
      statistically significant increase in frequency of hypocalcemia with the use of
      bisphosphonates compared with placebo or no treatment (RR 2.19, 95% CI 0.49 to
      9.74). The network meta-analysis did not show any differences in the incidence of
      hypocalcemia, renal dysfunction and gastrointestinal toxicity between the
      bisphosphonates used. AUTHORS' CONCLUSIONS: Use of bisphosphonates in patients
      with MM reduces pathological vertebral fractures, SREs and pain. Assuming a
      baseline risk of 20% to 50% for vertebral fracture without treatment, between 8
      and 20 MM patients should be treated to prevent vertebral fracture(s) in one
      patient. Assuming a baseline risk of 31% to 76% for pain amelioration without
      treatment, between 5 and 13 MM patients should be treated to reduce pain in one
      patient. With a baseline risk of 35% to 86% for SREs without treatment, between 6
      and 15 MM patients should be treated to prevent SRE(s) in one patient. Overall,
      there were no significant adverse effects associated with the administration of
      bisphosphonates identified in the included RCTs. We found no evidence of
      superiority of any specific aminobisphosphonate (zoledronate, pamidronate or
      ibandronate) or nonaminobisphosphonate (etidronate or clodronate) for any
      outcome. However, zoledronate appears to be superior to placebo and etidronate in
      improving OS.

PMID- 22592685
TI  - Anti-leukotriene agents compared to inhaled corticosteroids in the management of
      recurrent and/or chronic asthma in adults and children.
AB  - BACKGROUND: Anti-leukotrienes (5-lipoxygenase inhibitors and leukotriene
      receptors antagonists) serve as alternative monotherapy to inhaled
      corticosteroids (ICS) in the management of recurrent and/or chronic asthma in
      adults and children. OBJECTIVES: To determine the safety and efficacy of anti
      leukotrienes compared to inhaled corticosteroids as monotherapy in adults and
      children with asthma and to provide better insight into the influence of patient
      and treatment characteristics on the magnitude of effects. SEARCH METHODS: We
      searched MEDLINE (1966 to Dec 2010), EMBASE (1980 to Dec 2010), CINAHL (1982 to
      Dec 2010), the Cochrane Airways Group trials register, and the Cochrane Central
      Register of Controlled Trials (Dec 2010), abstract books, and reference lists of
      review articles and trials. We contacted colleagues and the international
      headquarters of anti-leukotrienes producers. SELECTION CRITERIA: We included
      randomised trials that compared anti-leukotrienes with inhaled corticosteroids as
      monotherapy for a minimum period of four weeks in patients with asthma aged two
      years and older. DATA COLLECTION AND ANALYSIS: Two review authors independently
      assessed the methodological quality of trials and extracted data. The primary
      outcome was the number of patients with at least one exacerbation requiring
      systemic corticosteroids. Secondary outcomes included patients with at least one
      exacerbation requiring hospital admission, lung function tests, indices of
      chronic asthma control, adverse effects, withdrawal rates and biological
      inflammatory markers. MAIN RESULTS: Sixty-five trials met the inclusion criteria
      for this review. Fifty-six trials (19 paediatric trials) contributed data
      (representing total of 10,005 adults and 3,333 children); 21 trials were of high
      methodological quality; 44 were published in full-text. All trials pertained to
      patients with mild or moderate persistent asthma. Trial durations varied from
      four to 52 weeks. The median dose of inhaled corticosteroids was quite
      homogeneous at 200 ug/day of microfine hydrofluoroalkane-propelled beclomethasone
      or equivalent (HFA-BDP eq). Patients treated with anti-leukotrienes were more
      likely to suffer an exacerbation requiring systemic corticosteroids (N = 6077
      participants; risk ratio (RR) 1.51, 95% confidence interval (CI) 1.17, 1.96). For
      every 28 (95% CI 15 to 82) patients treated with anti-leukotrienes instead of
      inhaled corticosteroids, there was one additional patient with an exacerbation
      requiring rescue systemic corticosteroids. The magnitude of effect was
      significantly greater in patients with moderate compared with those with mild
      airway obstruction (RR 2.03, 95% CI 1.41, 2.91 versus RR 1.25, 95% CI 0.97,
      1.61), but was not significantly influenced by age group (children representing
      23% of the weight versus adults), anti-leukotriene used, duration of
      intervention, methodological quality, and funding source. Significant group
      differences favouring inhaled corticosteroids were noted in most secondary
      outcomes including patients with at least one exacerbation requiring hospital
      admission (N = 2715 participants; RR 3.33; 95% CI 1.02 to 10.94), the change from
      baseline FEV(1) (N = 7128 participants; mean group difference (MD) 110 mL, 95% CI
      140 to 80) as well as other lung function parameters, asthma symptoms, nocturnal
      awakenings, rescue medication use, symptom-free days, the quality of life,
      parents' and physicians' satisfaction. Anti-leukotriene therapy was associated
      with increased risk of withdrawals due to poor asthma control (N = 7669
      participants; RR 2.56; 95% CI 2.01 to 3.27). For every thirty one (95% CI 22 to
      47) patients treated with anti-leukotrienes instead of inhaled corticosteroids,
      there was one additional withdrawal due to poor control. Risk of side effects was
      not significantly different between both groups. AUTHORS' CONCLUSIONS: As
      monotherapy, inhaled corticosteroids display superior efficacy to anti
      leukotrienes in adults and children with persistent asthma; the superiority is
      particularly marked in patients with moderate airway obstruction. On the basis of
      efficacy, the results support the current guidelines' recommendation that inhaled
      corticosteroids remain the preferred monotherapy. 

PMID- 22592689
TI  - Symptomatic treatment of the cough in whooping cough.
AB  - BACKGROUND: The worldwide incidence of whooping cough (pertussis) has been
      estimated at 48.5 million cases and nearly 295,000 deaths per year. In low-income
      countries, the case-fatality rate among infants may be as high as 4%. Much of the
      morbidity of whooping cough in children and adults is due to the effects of the
      paroxysmal cough. Cough treatments proposed include corticosteroids, beta 2
      adrenergic agonists, pertussis-specific immunoglobulin, antihistamines and
      possibly leukotriene receptor antagonists (LTRAs). OBJECTIVES: To assess the
      effectiveness and safety of interventions to reduce the severity of paroxysmal
      cough in whooping cough in children and adults. SEARCH METHODS: We updated
      searches of the Cochrane Central Register of Controlled Trials (CENTRAL Issue 2,
      2012), which contains the Cochrane Acute Respiratory Infections Group's
      Specialised Register, the Database of Abstracts of Reviews of Effects (DARE Issue
      2, 2012) accessed from The Cochrane Library, MEDLINE (1950 to January 2012),
      EMBASE (1980 to January 2012), AMED (1985 to January 2012), CINAHL (1980 to
      January 2012) and LILACS (January 2012). We searched Current Controlled Trials to
      identify trials in progress. SELECTION CRITERIA: We selected randomised
      controlled trials (RCTs) and quasi-RCTs of any intervention (excluding
      antibiotics and vaccines) to suppress the cough in whooping cough. DATA
      COLLECTION AND ANALYSIS: Two review authors (SB, MT) independently selected
      trials, extracted data and assessed the quality of each trial for this review in
      2009. Two review authors (SB, KW) independently reviewed additional studies
      identified by the updated search in 2012. The primary outcome was frequency of
      paroxysms of coughing. Secondary outcomes were frequency of vomiting, frequency
      of whoop, frequency of cyanosis (turning blue), development of serious
      complications, mortality from any cause, side effects due to medication,
      admission to hospital and duration of hospital stay.  MAIN RESULTS: Ten trials
      were included of varying sample sizes (N = 9 to 135) from high-income countries.
      Study quality was generally poor. Included studies did not show a statistically
      significant benefit for any of the interventions. Only six trials including a
      total of 196 participants reported data in sufficient detail for analysis.
      Diphenhydramine did not change coughing episodes; the mean difference (MD) of
      coughing spells per 24 hours was 1.9; 95% confidence interval (CI) - 4.7 to 8.5.
      One study on pertussis immunoglobulin reported a possible mean reduction of -3.1
      whoops per 24 hours (95% CI -6.2 to 0.02) but no change in hospital stay (MD -0.7
      days; 95% CI -3.8 to 2.4). Dexamethasone did not show a clear decrease in length
      of hospital stay (MD -3.5 days; 95% CI -15.3 to 8.4) and salbutamol showed no
      change in coughing paroxysms per 24 hours (MD -0.2; 95% CI -4.1 to 3.7). Only one
      trial comparing pertussis immunoglobulin versus placebo reported data on adverse
      events: 4.3% in the treatment group (rash) versus 5.3% in the placebo group
      (loose stools, pain and swelling at injection site). AUTHORS' CONCLUSIONS: There
      is insufficient evidence to draw conclusions about the effectiveness of
      interventions for the cough in whooping cough.

PMID- 22592690
TI  - Removal of nail polish and finger rings to prevent surgical infection.
AB  - BACKGROUND: Surgical wound infections may be caused by the transfer of bacteria
      from the hands of surgical teams to patients during operations. Surgical
      scrubbing prior to surgery reduces the number of bacteria on the skin, but
      wearing rings and nail polish on the fingers may reduce the efficacy of
      scrubbing, as bacteria may remain in microscopic imperfections of nail polish and
      on the skin beneath rings. OBJECTIVES: To assess the effect of the presence or
      absence of rings and nail polish on the hands of the surgical scrub team on
      postoperative wound infection rates. SEARCH METHODS: For this update, we searched
      The Cochrane Wounds Group Specialised Register (searched 27 January 2012); The
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library
      2012, Issue 1); Ovid MEDLINE (2010 to January Week 2 2012); Ovid MEDLINE (In
      Process & Other Non-Indexed Citations, January 26, 2012); Ovid EMBASE (2010 to
      2012 Week 03); and EBSCO CINAHL (2010 to January 6 2012). SELECTION CRITERIA:
      Randomised controlled trials (RCTs) evaluating the effect of wearing or removing
      finger rings and nail polish on the efficacy of the surgical scrub and
      postoperative wound infection rate. DATA COLLECTION AND ANALYSIS: All abstracts
      were checked against a checklist to determine whether they fulfilled the
      inclusion criteria. Full reports of relevant studies were obtained. Excluded
      trial reports were checked by all authors to ensure appropriate exclusion. MAIN
      RESULTS: We identified: no new trials; no RCTs that compared wearing of rings
      with the removal of rings; and no trials of nail polish versus no nail polish
      that measured surgical infection rates. We found one small RCT (102 scrub nurses)
      that evaluated the effect of nail polish on the number of bacterial colony
      forming units left on hands after pre-operative surgical scrubbing. Nurses had
      either unpolished nails, freshly-applied nail polish (less than two days old), or
      old nail polish (more than four days old). There were no significant differences
      in the number of bacteria on hands between the groups before and after surgical
      scrubbing. AUTHORS' CONCLUSIONS: No trials have investigated whether wearing nail
      polish or finger rings affects the rate of surgical wound infection. There is
      insufficient evidence to determine whether wearing nail polish affects the number
      of bacteria on the skin post-scrub.

PMID- 22592692
TI  - Hospital at home for acute exacerbations of chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: Hospital at home schemes are a recently adopted method of service
      delivery for the management of acute exacerbations of chronic obstructive
      pulmonary disease (COPD) aimed at reducing demand for acute hospital inpatient
      beds and promoting a patient-centred approach through admission avoidance.
      However, evidence in support of such a service is contradictory. OBJECTIVES: To
      evaluate the efficacy of hospital at home compared to hospital inpatient care in
      acute exacerbations of COPD. SEARCH METHODS: Trials were identified from searches
      of electronic databases, including CENTRAL, MEDLINE, EMBASE, and the Cochrane
      Airways Group Register (CAGR). The review authors checked the reference lists of
      included trials. The CAGR was searched up to February 2012. The additional
      databases were searched up to October 2010. SELECTION CRITERIA: We considered
      randomised controlled trials where patients presented to the emergency department
      with an exacerbation of their COPD. Studies must not have recruited patients for
      whom treatment at home is usually not viewed as an responsible option (e.g.
      patients with an impaired level of consciousness, acute confusion, acute changes
      on the radiograph or electrocardiogram, arterial pH less than 7.35, concomitant
      medical conditions). DATA COLLECTION AND ANALYSIS: Two review authors
      independently selected articles for inclusion, assessed the risk of bias and
      extracted data for each of the included trials. MAIN RESULTS: Eight trials with
      870 patients were included in the review and showed a significant reduction in
      readmission rates for hospital at home compared with hospital inpatient care of
      acute exacerbations of COPD (risk ratio (RR)0.76; 95% confidence interval (CI)
      from 0.59 to 0.99; P=0.04). Moreover, we observed a trend towards lower mortality
      in the hospital at home group, but the pooled effect estimate did not reach
      statistical significance (RR 0.65, 95% CI 0.40 to 1.04, P = 0.07). For health
      related quality of life, lung function (FEV1) and direct costs, the quality of
      the available evidence is in general too weak to make firm conclusions. AUTHORS'
      CONCLUSIONS: Selected patients presenting to hospital emergency departments with
      acute exacerbations of COPD can be safely and successfully treated at home with
      support from respiratory nurses. We found evidence of moderate quality that
      hospital at home may be advantageous with respect to readmission rates in these
      patients. Treatment of acute exacerbation of COPD in hospital at home also show a
      trend towards reduced mortality rate when compared with conventional inpatient
      treatment, but these results did not reach statistical significance (moderate
      quality evidence). For other outcomes than readmission and mortality rate, we
      assessed the evidence to be of low or very low quality.

PMID- 22592693
TI  - Cephalic version by moxibustion for breech presentation.
AB  - BACKGROUND: Moxibustion (a type of Chinese medicine which involves burning a herb
      close to the skin) to the acupuncture point Bladder 67 (BL67) (Chinese name
      Zhiyin), located at the tip of the fifth toe, has been proposed as a way of
      correcting breech presentation. OBJECTIVES: To examine the effectiveness and
      safety of moxibustion on changing the presentation of an unborn baby in the
      breech position, the need for external cephalic version (ECV), mode of birth, and
      perinatal morbidity and mortality for breech presentation. SEARCH METHODS: We
      searched the Cochrane Pregnancy and Childbirth Group's Trials Register (26 March
      2012), MEDLINE (1966 to 1 August 2011), EMBASE (1980 to August 2011), CINAHL
      (1982 to 1 August 2011), MIDIRS (1982 to 1 August 2011) and AMED (1985 to 1
      August 2011) and searched bibliographies of relevant papers. SELECTION CRITERIA:
      The inclusion criteria were published and unpublished randomised controlled
      trials comparing moxibustion (either alone or in combination with acupuncture or
      postural techniques) with a control group (no moxibustion), or other methods
      (e.g. external cephalic version, acupuncture, postural techniques) in women with
      a singleton breech presentation. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed eligibility and trial quality and extracted data. The
      outcome measures were baby's presentation at birth, need for external cephalic
      version, mode of birth, perinatal morbidity and mortality, maternal complications
      and maternal satisfaction, and adverse events. MAIN RESULTS: Six new trials have
      been added to this updated review. One trial has been moved to studies awaiting
      classification while further data are being requested. This updated review now
      includes a total of eight trials (involving 1346 women). Meta-analyses were
      undertaken (where possible) for the main and secondary outcomes. Moxibustion was
      not found to reduce the number of non-cephalic presentations at birth compared
      with no treatment (P = 0.45). Moxibustion resulted in decreased use of oxytocin
      before or during labour for women who had vaginal deliveries compared with no
      treatment (risk ratio (RR) 0.28, 95% confidence interval (CI) 0.13 to 0.60).
      Moxibustion was found to result in fewer non-cephalic presentations at birth
      compared with acupuncture (RR 0.25, 95% CI 0.09 to 0.72). When combined with
      acupuncture, moxibustion resulted in fewer non-cephalic presentations at birth
      (RR 0.73, 95% CI 0.57 to 0.94), and fewer births by caesarean section (RR 0.79,
      95% CI 0.64 to 0.98) compared with no treatment. When combined with a postural
      technique, moxibustion was found to result in fewer non-cephalic presentations at
      birth compared with the postural technique alone (RR 0.26, 95% CI 0.12 to 0.56).
      AUTHORS' CONCLUSIONS: This review found limited evidence to support the use of
      moxibustion for correcting breech presentation. There is some evidence to suggest
      that the use of moxibustion may reduce the need for oxytocin. When combined with
      acupuncture, moxibustion may result in fewer births by caesarean section; and
      when combined with postural management techniques may reduce the number of non
      cephalic presentations at birth, however, there is a need for well-designed
      randomised controlled trials to evaluate moxibustion for breech presentation
      which report on clinically relevant outcomes as well as the safety of the
      intervention.

PMID- 22592691
TI  - Early skin-to-skin contact for mothers and their healthy newborn infants.
AB  - BACKGROUND: Mother-infant separation postbirth is common in Western culture.
      Early skin-to-skin contact (SSC) begins ideally at birth and involves placing the
      naked baby, head covered with a dry cap and a warm blanket across the back, prone
      on the mother's bare chest. According to mammalian neuroscience, the intimate
      contact inherent in this place (habitat) evokes neurobehaviors ensuring
      fulfillment of basic biological needs. This time may represent a
      psychophysiologically 'sensitive period' for programming future physiology and
      behavior. OBJECTIVES: To assess the effects of early SSC on breastfeeding,
      physiological adaptation, and behavior in healthy mother-newborn dyads. SEARCH
      METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (30 November 2011), made personal contact with trialists, and consulted
      the bibliography on kangaroo mother care (KMC) maintained by Dr. Susan Ludington.
      SELECTION CRITERIA: Randomized controlled trials comparing early SSC with usual
      hospital care. DATA COLLECTION AND ANALYSIS: We independently assessed trial
      quality and extracted data. Study authors were contacted for additional
      information. MAIN RESULTS: Thirty-four randomized controlled trials were included
      involving 2177 participants (mother-infant dyads). Data from more than two trials
      were available for only eight outcome measures. For primary outcomes, we found a
      statistically significant positive effect of early SSC on breastfeeding at one to
      four months postbirth (13 trials; 702 participants) (risk ratio (RR) 1.27, 95%
      confidence interval (CI) 1.06 to 1.53, and SSC increased breastfeeding duration
      (seven trials; 324 participants) (mean difference (MD) 42.55 days, 95% CI -1.69
      to 86.79) but the results did not quite reach statistical significance (P =
      0.06). Late preterm infants had better cardio-respiratory stability with early
      SSC (one trial; 31 participants) (MD 2.88, 95% CI 0.53 to 5.23). Blood glucose 75
      to 90 minutes following the birth was significantly higher in SSC infants (two
      trials, 94 infants) (MD 10.56 mg/dL, 95% CI 8.40 to 12.72).The overall
      methodological quality of trials was mixed, and there was high heterogeneity for
      some outcomes. AUTHORS' CONCLUSIONS: Limitations included methodological quality,
      variations in intervention implementation, and outcomes. The intervention appears
      to benefit breastfeeding outcomes, and cardio-respiratory stability and decrease
      infant crying, and has no apparent short- or long-term negative effects. Further
      investigation is recommended. To facilitate meta-analysis, future research should
      be done using outcome measures consistent with those in the studies included
      here. Published reports should clearly indicate if the intervention was SSC with
      time of initiation and duration and include means, standard deviations and exact
      probability values.

PMID- 22592694
TI  - Totally implantable vascular access devices for cystic fibrosis.
AB  - BACKGROUND: Totally implantable vascular access devices are widely used in people
      with cystic fibrosis to provide intermittent venous access for therapeutic
      infusions. Their use is associated with some complications such as thrombosis,
      embolism and infection. OBJECTIVES: To assess if totally implantable venous
      access devices provide a safe and effective route for venous access for
      intermittent administration of intravenous antibiotics in people with cystic
      fibrosis. Also to assess strategies to reduce possible complications of totally
      implantable venous access devices (e.g. anticoagulants to reduce the risk of
      thrombosis). SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic
      Disorders Group Trials Register which comprises references identified from
      comprehensive electronic database searches, handsearches of relevant journals and
      abstract books of conference proceedings.Date of the most recent search: 05 April
      2012. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials which
      compared the use of totally implantable venous access devices in people with
      cystic fibrosis to other means of vascular access, trials which compared the
      different types of these devices against each other and trials which assessed
      strategies to reduce complications of these devices. DATA COLLECTION AND
      ANALYSIS: No relevant trials were identified. MAIN RESULTS: No trials were
      included in this review. AUTHORS' CONCLUSIONS: Totally implantable vascular
      access devices are widely used in people with cystic fibrosis to provide
      intermittent venous access for therapeutic infusions. Reports of their use in
      people with cystic fibrosis suggest that they are safe and effective. These
      reports also suggest that certain interventions might reduce the risk of
      complications; however, it is disappointing that these reports have not been
      assessed by randomised controlled trials. This systematic review identifies the
      need for a multicentre randomised controlled trial assessing both efficacy and
      possible adverse effects of totally implantable venous access devices in cystic
      fibrosis.

PMID- 22592695
TI  - Prophylactic platelet transfusion for prevention of bleeding in patients with
      haematological disorders after chemotherapy and stem cell transplantation.
AB  - BACKGROUND: Platelet transfusions are used in modern clinical practice to prevent
      and treat bleeding in thrombocytopenic patients with bone marrow failure.
      Although considerable advances have been made in platelet transfusion therapy in
      the last 40 years, some areas continue to provoke debate especially concerning
      the use of prophylactic platelet transfusions for the prevention of
      thrombocytopenic bleeding. OBJECTIVES: To determine the most effective use of
      platelet transfusion for the prevention of bleeding in patients with
      haematological disorders undergoing chemotherapy or stem cell transplantation.
      SEARCH METHODS: This is an update of a Cochrane review first published in 2004.
      We searched for randomised controlled trials (RCTs) in the Cochrane Central
      Register of Controlled Trials (CENTRAL Issue 4, 2011), MEDLINE (1950 to Nov
      2011), EMBASE (1980 to Nov 2011) and CINAHL (1982 to Nov 2011), using adaptations
      of the Cochrane RCT search filter, the UKBTS/SRI Transfusion Evidence Library,
      and ongoing trial databases to 10 November 2011. SELECTION CRITERIA: RCTs
      involving transfusions of platelet concentrates, prepared either from individual
      units of whole blood or by apheresis, and given to prevent bleeding in patients
      with haematological disorders. Four different types of prophylactic platelet
      transfusion trial were included. DATA COLLECTION AND ANALYSIS: In the original
      review one author initially screened all electronically derived citations and
      abstracts of papers, identified by the review search strategy, for relevancy. Two
      authors performed this task in the updated review. Two authors independently
      assessed the full text of all potentially relevant trials for eligibility. Two
      authors completed data extraction independently. We requested missing data from
      the original investigators as appropriate. MAIN RESULTS: There were 18 trials
      that were eligible for inclusion, five of these were still ongoing.Thirteen
      completed published trials (2331 participants) were included for analysis in the
      review. The original review contained nine trials (718 participants). This
      updated review includes six new trials (1818 participants).Two trials (205
      participants) in the original review are now excluded because fewer than 80% of
      participants had a haematological disorder.The four different types of
      prophylactic platelet transfusion trial, that were the focus of this review, were
      included within these thirteen trials.Three trials compared prophylactic platelet
      transfusions versus therapeutic-only platelet transfusions. There was no
      statistical difference between the number of participants with clinically
      significant bleeding in the therapeutic and prophylactic arms but the confidence
      interval was wide (RR 1.66; 95% CI 0.9 to 3.04).The time taken for a clinically
      significant bleed to occur was longer in the prophylactic platelet transfusion
      arm. There was a clear reduction in platelet transfusion usage in the therapeutic
      arm. There was no statistical difference between the number of participants in
      the therapeutic and prophylactic arms with platelet refractoriness, the only
      adverse event reported.Three trials compared different platelet count thresholds
      to trigger administration of prophylactic platelet transfusions. No statistical
      difference was seen in the number of participants with clinically significant
      bleeding (RR 1.35; 95% CI 0.95 to 1.9), however, this type of bleeding occurred
      on fewer days in the group of patients transfused at a higher platelet count
      threshold (RR 1.72; 95% CI 1.33 to 2.22).The lack of a difference seen for the
      number of participants with clinically significant bleeding may be due to the
      studies, in combination, having insufficient power to demonstrate a difference,
      or due to masking of the effect by a higher number of protocol violations in the
      groups of patients with a lower platelet count threshold. Using a lower platelet
      count threshold led to a significant reduction in the number of platelet
      transfusions used. There were no statistical differences in the number of adverse
      events reported between the two groups.Six trials compared different doses of
      prophylactic platelet transfusions. There was no evidence to suggest that using a
      lower platelet transfusion dose increased: the number of participants with
      clinically significant (WHO grade 2 or above) (RR 1.02; 95% CI 0.93 to 1.11), or
      life-threatening (WHO grade 4) bleeding (RR 1.87; 95% CI 0.86 to 4.08). A higher
      platelet transfusion dose led to a reduction in the number of platelet
      transfusion episodes, but an increase in total platelet utilisation. Only one
      adverse event, wheezing after transfusion, had a significantly higher incidence
      when standard and high dose transfusions were compared but this difference was
      not seen when low dose and high dose transfusions were compared. It is therefore
      likely to be a type I error (false positive).One small trial compared
      prophylactic platelet transfusions versus platelet-poor plasma. The risk of a
      significant bleed was decreased in the prophylactic platelet transfusion arm (RR
      0.47; 95% CI 0.23 to 0.95) and this was statistically significant.All studies had
      threats to validity; the majority of these were due to methodology of the studies
      not being described in adequate detail.Although it was not the main focus of the
      review, it was interesting to note that in one of the pre-specified sub-group
      analyses (treatment type) two studies showed that patients receiving an
      autologous transplant have a lower risk of bleeding than patients receiving
      intensive chemotherapy or an allogeneic transplant (RR 0.73, 95% CI 0.65 to
      0.82). AUTHORS' CONCLUSIONS: These conclusions refer to the four different types
      of platelet transfusion trial separately. Firstly, there is no evidence that a
      prophylactic platelet transfusion policy prevents bleeding. Two large trials
      comparing a therapeutic versus prophylactic platelet transfusion strategy, that
      have not yet been published, should provide important new data on this
      comparison. Secondly, there is no evidence, at the moment, to suggest a change
      from the current practice of using a platelet count of 10 x 10(9)/L. However, the
      evidence for a platelet count threshold of 10 x 10(9)/L being equivalent to 20 x
      10(9)/L is not as definitive as it would first appear and further research is
      required. Thirdly, platelet dose does not affect the number of patients with
      significant bleeding, but whether it affects number of days each patient bleeds
      for is as yet undetermined. There is no evidence that platelet dose affects the
      incidence of WHO grade 4 bleeding.Prophylactic platelet transfusions were more
      effective than platelet-poor plasma at preventing bleeding.

PMID- 22592696
TI  - Treatment for avascular necrosis of bone in people with sickle cell disease.
AB  - BACKGROUND: Avascular necrosis of bone is a frequent and severe complication of
      sickle cell disease and its treatment is not standardised. OBJECTIVES: To
      determine the impact of any surgical procedure compared with other surgical
      interventions or non-surgical procedures, on avascular necrosis of bone in people
      with sickle cell disease in terms of efficacy and safety. SEARCH METHODS: We
      searched the Cochrane Cystic Fibrosis and Genetic Disorders Group
      Haemoglobinopathies Trials Register, comprising references identified from
      comprehensive electronic database searches and handsearches of relevant journals
      and abstract books of conference proceedings. Additional trials were sought from
      the reference lists of papers identified by the search strategy.Date of the most
      recent search of the Group's Haemoglobinopathies Trials Register: 21 February
      2012. SELECTION CRITERIA: Randomised clinical trials comparing specific therapies
      for avascular necrosis of bone in people with sickle cell disease. DATA
      COLLECTION AND ANALYSIS: Each author independently extracted data and assessed
      trial quality. Since only one trial was identified, meta-analysis was not
      possible. MAIN RESULTS: One trial (46 participants) was eligible for inclusion.
      After randomisation eight participants were withdrawn, mainly because they
      declined to participate in the trial. Data were analysed for 38 participants at
      the end of the trial. After a mean follow up of three years, hip core
      decompression and physical therapy did not show clinical improvement when
      compared with physical therapy alone using the score from the original trial (an
      improvement of 18.1 points for those treated with intervention therapy versus an
      improvement of 15.7 points with control therapy). There was no significant
      statistical difference between groups regarding major complications (hip pain,
      relative risk (RR) 0.95 (95% confidence interval (CI) 0.56 to 1.60; vaso
      occlusive crises, RR 1.14 (95% CI 0.72 to 1.80); and acute chest syndrome, RR
      1.06 (95% CI 0.44 to 2.56)). This trial did not report results on mortality or
      quality of life. AUTHORS' CONCLUSIONS: We found no evidence that adding hip core
      decompression to physical therapy achieves clinical improvement in people with
      sickle cell disease with avascular necrosis of bone compared to physical therapy
      alone. However, we highlight that our conclusion is based on one trial with high
      attrition rates. Further randomised controlled trials are necessary to evaluate
      the role of hip-core depression for this clinical condition. Endpoints should
      focus on participants' subjective experience (e.g. quality of life and pain) as
      well as more objective 'time-to-event' measures (e.g. mortality, survival, hip
      longevity). The availability of participants to allow adequate trial power will
      be a key consideration for endpoint choice.

PMID- 22592697
TI  - Herbal medicines for advanced colorectal cancer.
AB  - BACKGROUND: Herbal medicine has been widely used in patients with advanced
      colorectal cancer in China, but its efficacy has not been confirmed. OBJECTIVES:
      To evaluate the beneficial effect and safety on Chinese herbal medicine therapy
      for advanced stage colorectal cancer, and it's influence on the patients' quality
      of life. SEARCH METHODS: The following electronic databases were searched: BIOSIS
      Previews, Cochrane Controlled Trials Register, Medline EMBASE, Biological
      Abstracts, until Aug. 2011. Manual searching was performed on 16 types of Chinese
      journals which started from their respective first publication dates, as well as
      unpublished conference proceedings. No language restriction was applied.
      SELECTION CRITERIA: Randomized or quasi-randomised controlled trials on the
      treatment of advanced stage colorectal cancer by herbal medicines or herbal
      medicines combined with chemotherapy, regardless of blinding. DATA COLLECTION AND
      ANALYSIS: The data were extracted independently by two reviewers. Methodological
      quality of the included in trials was assessed according to the following
      parameters: randomisation, allocation concealment, double blinding, and drop-out
      rates. MAIN RESULTS: A total of 20 randomised controlled trials with 1304
      participants were identified. All the 20 trials compared the use of herbal
      medicines with chemotherapy and chemotherapy alone in the treatment of advanced
      stage colorectal cancers.Compared with chemotherapy alone, the use of Quxie
      capsule combined with chemotherapy could decrease mortality rate (RR 0.17, 95% CI
      0.03 to 0.97); the use of Jianpi Jiedu formula, Xiaozheng formula and Yiqi Huoxue
      herbal medicine combined with chemotherapy respectively could improve 1-year
      survival rate significantly; the use of Xiaozheng Formula in conjunction with
      chemotherapy could improve 3-year survival rate. There were 10 herbal medicines
      showing benefit in improving quality of life. Herbal medicines did not show
      additional benefit in response rate or stability rate. No trials reported serious
      adverse effect from herbal medicine. AUTHORS' CONCLUSIONS: Some herbal medicines
      combined chemotherapy compared with chemotherapy alone showed more beneficial
      effects in improving 1-year, 3-year survival and quality of life.

PMID- 22592698
TI  - Elective repeat caesarean section versus induction of labour for women with a
      previous caesarean birth.
AB  - BACKGROUND: When a woman has had a previous caesarean birth and requires
      induction of labour in a subsequent pregnancy, there are two options for her
      care: elective repeat caesarean or planned induction of labour. While there are
      risks and benefits for both elective repeat caesarean birth and planned induction
      of labour, current sources of information are limited to non-randomised cohort
      studies. Studies designed in this way have significant potential for bias and
      consequently conclusions based on these results are limited in their reliability
      and should be interpreted with caution. OBJECTIVES: To assess, using the best
      available evidence, the benefits and harms of elective repeat caesarean section
      and planned induction of labour for women with a previous caesarean birth. SEARCH
      METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (27 January 2012). SELECTION CRITERIA: Randomised controlled trials with
      reported data that compared outcomes in mothers and babies who planned a repeat
      elective caesarean section with outcomes in women who planned induction of
      labour, where a previous birth had been by caesarean. DATA COLLECTION AND
      ANALYSIS: There was no data extraction performed. MAIN RESULTS: There were no
      randomised controlled trials identified. AUTHORS' CONCLUSIONS: Planned elective
      repeat caesarean section and planned induction of labour for women with a prior
      caesarean birth are both associated with benefits and harms. Evidence for these
      care practices is drawn from non-randomised studies, associated with potential
      bias. Any results and conclusions must therefore be interpreted with caution.
      Randomised controlled trials are required to provide the most reliable evidence
      regarding the benefits and harms of both planned elective repeat caesarean
      section and planned induction of labour for women with a previous caesarean
      birth.

PMID- 22592699
TI  - Hyperbaric oxygen therapy for late radiation tissue injury.
AB  - BACKGROUND: Cancer is a significant global health problem. Radiotherapy is a
      treatment for many cancers and about 50% of patients having radiotherapy with be
      long-term survivors. Some will experience late radiation tissue injury (LRTI)
      developing months or years later. Hyperbaric oxygen therapy (HBOT) has been
      suggested as a treatment for LRTI based upon the ability to improve the blood
      supply to these tissues. It is postulated that HBOT may result in both healing of
      tissues and the prevention of problems following surgery. OBJECTIVES: To assess
      the benefits and harms of HBOT for treating or preventing LRTI. SEARCH METHODS:
      In March 2011 we updated the searches of the Cochrane Central Register of
      Controlled Trials (CENTRAL), (The Cochrane Library, Issue 1), MEDLINE, EMBASE,
      DORCTIHM and reference lists of articles. SELECTION CRITERIA: Randomised
      controlled trials (RCTs) comparing the effect of HBOT versus no HBOT on LRTI
      prevention or healing. DATA COLLECTION AND ANALYSIS: Three review authors
      independently evaluated the quality of the relevant trials using the guidelines
      of the Cochrane Handbook for Systematic Reviews of Interventions and extracted
      the data from the included trials. MAIN RESULTS: Eleven trials contributed to
      this review (669 participants). For pooled analyses, investigation of
      heterogeneity suggested important variability between trials but there was some
      evidence that HBOT is more likely to achieve mucosal coverage with
      osteoradionecrosis (ORN) (risk ratio (RR) 1.3; 95% confidence interval (CI) 1.1
      to 1.6, P = 0.003, number needed to treat for an additional beneficial outcome
      (NNTB) 5). From single studies there was a significantly increased chance of
      improvement or cure following HBOT for radiation proctitis (RR 1.72; 95% CI 1.0
      to 2.9, P = 0.04, NNTB 5), and following both surgical flaps (RR 8.7; 95% CI 2.7
      to 27.5, P = 0.0002, NNTB = 4) and hemimandibulectomy (RR 1.4; 95% CI 1.1 to 1.8,
      P = 0.001, NNTB 5). There was also a significantly improved probability of
      healing irradiated tooth sockets following dental extraction (RR 1.4; 95% CI 1.1
      to 1.7, P = 0.009, NNTB 4).There was no evidence of benefit in clinical outcomes
      with established radiation injury to neural tissue, and no data reported on the
      use of HBOT to treat other manifestations of LRTI. These trials did not report
      adverse effects. AUTHORS' CONCLUSIONS: These small trials suggest that for people
      with LRTI affecting tissues of the head, neck, anus and rectum, HBOT is
      associated with improved outcome. HBOT also appears to reduce the chance of ORN
      following tooth extraction in an irradiated field. There was no such evidence of
      any important clinical effect on neurological tissues. The application of HBOT to
      selected patients and tissues may be justified. Further research is required to
      establish the optimum patient selection and timing of any therapy. An economic
      evaluation should be undertaken.

PMID- 22592700
TI  - Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial
      fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most frequent sustained arrhythmia.
      AF recurs frequently after restoration of normal sinus rhythm. Antiarrhythmic
      drugs have been widely used to prevent recurrence, but the effect of these drugs
      on mortality and other clinical outcomes is unclear. OBJECTIVES: To determine, in
      patients who recovered sinus rhythm after AF, the effect of long-term treatment
      with antiarrhythmic drugs on death, stroke and embolism, adverse effects, pro
      arrhythmia, and recurrence of AF. SEARCH METHODS: We updated the searches of
      CENTRAL on The Cochrane Libary (Issue 1 of 4, 2010), MEDLINE (1950 to February
      2010) and EMBASE (1966 to February 2010). The reference lists of retrieved
      articles, recent reviews and meta-analyses were checked. SELECTION CRITERIA: Two
      independent reviewers selected randomised controlled trials comparing any
      antiarrhythmic with a control (no treatment, placebo or drugs for rate control)
      or with another antiarrhythmic, in adults who had AF and in whom sinus rhythm was
      restored. Post-operative AF was excluded. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently assessed quality and extracted data. Studies were pooled,
      if appropriate, using Peto odds ratio (OR). All results were calculated at one
      year of follow-up. MAIN RESULTS: In this update, 11 new studies met inclusion
      criteria, making a total of 56 included studies, comprising 20,771 patients.
      Compared with controls, class IA drugs quinidine and disopyramide (OR 2.39, 95%
      confidence interval (95%CI) 1.03 to 5.59, number needed to harm (NNH) 109, 95%CI
      34 to 4985) and sotalol (OR 2.47, 95%CI 1.2 to 5.05, NNH 166, 95%CI 61 to 1159)
      were associated with increased all-cause mortality. Other antiarrhythmics did not
      seem to modify mortality.Several class IA (disopyramide, quinidine), IC
      (flecainide, propafenone) and III (amiodarone, dofetilide, dronedarone, sotalol)
      drugs significantly reduced recurrence of AF (OR 0.19 to 0.70, number needed to
      treat (NNT) 3 to 16). Beta-blockers (metoprolol) also reduced significantly AF
      recurrence (OR 0.62, 95% CI 0.44 to 0.88, NNT 9).All analysed drugs increased
      withdrawals due to adverse affects and all but amiodarone, dronedarone and
      propafenone increased pro-arrhythmia. We could not analyse other outcomes because
      few original studies reported them. AUTHORS' CONCLUSIONS: Several class IA, IC
      and III drugs, as well as class II (beta-blockers), are moderately effective in
      maintaining sinus rhythm after conversion of atrial fibrillation. However, they
      increase adverse events, including pro-arrhythmia, and some of them
      (disopyramide, quinidine and sotalol) may increase mortality. Possible benefits
      on clinically relevant outcomes (stroke, embolisms, heart failure) remain to be
      established.

PMID- 22592701
TI  - Uterine artery embolization for symptomatic uterine fibroids.
AB  - BACKGROUND: Uterine fibroids cause heavy prolonged bleeding, pain, pressure
      symptoms and subfertility. The traditional method of treatment has been surgery
      as medical therapies have not proven effective. Uterine artery embolization (UAE)
      has been reported to be an effective and safe alternative to treat fibroids in
      women not desiring future fertility. There is a significant body of evidence
      based on case controlled studies and case reports. This is an update of the
      review previously published in 2006. OBJECTIVES: To review the benefits and risks
      of uterine artery embolization (UAE) versus other medical or surgical
      interventions for symptomatic uterine fibroids. SEARCH METHODS: We searched the
      Cochrane Menstrual Disorders & Subfertility Group Trials register (searched
      November 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) in
      The Cochrane Library, 4th Quarter 2011), MEDLINE (1950 to November 2011) and
      EMBASE (January 1980 to November 2011). We also contacted authors of eligible
      RCTs for unpublished data. SELECTION CRITERIA: Randomised controlled trials
      (RCTs) of UAE versus any medical or surgical therapy for symptomatic uterine
      fibroids. DATA COLLECTION AND ANALYSIS: Two of the authors (AS and JKG) assessed
      the trials and extracted the data independently. MAIN RESULTS: Five RCTs were
      included in this review. Three trials compared UAE with abdominal hysterectomy in
      291 women. A fourth trial included 157 women and compared UAE with surgery (43
      hysterectomies and 8 myomectomies). The fifth trial included 121 women and
      compared UAE with myomectomy in women wishing to preserve fertility.There was
      moderately good evidence that there is no significant difference between UAE and
      surgery in patient satisfaction rates at two years (OR 0.69, 0.40 to 1.21, 516
      women, 5 trials) nor at five years (OR 0.90, 95% CI 0.45 to 1.80, 295 women, 2
      trials). There was very low level evidence suggesting that myomectomy may be
      associated with better fertility outcomes than UAE, but this analysis was
      restricted to the limited cohort of women (n=66) who tried to conceive in the
      single study of UAE versus myomectomy (live birth: OR 0.33, 95% CI 0.11 to 1.00;
      pregnancy: OR 0.29, 95% CI 0.10 to 0.85). There was no significant difference
      between the two interventions in the rate of major complications. Compared to
      surgery, UAE significantly reduced the length of the procedure, length of
      hospital stay and time to resumption of routine activities and also decreased the
      likelihood of needing a blood transfusion. However, UAE was associated with
      higher rates of minor short term and long term complications, more unscheduled
      readmissions after discharge and an increased surgical reintervention rate. This
      increase in the surgical reintervention rate may balance out the initial cost
      advantage of UAE (reinterventions within 2 years: OR 5.64, 95% CI 2.92 to 10.90,
      486 women, 4 trials; within 5 years: OR 5.79, 95% CI 2.65 to 12.65. 289 women, 2
      trials). There was no significant difference in ovarian failure rates at long
      term follow-up. AUTHORS' CONCLUSIONS: UAE appears to have an overall patient
      satisfaction rate similar to hysterectomy and myomectomy and offers an advantage
      with regards to a shorter hospital stay and a quicker return to routine
      activities. However, UAE is associated with a higher rate of minor complications
      and an increased likelihood of requiring surgical intervention within two to five
      years of the initial procedure. There is very low level evidence suggesting that
      myomectomy may be associated with better fertility outcomes than UAE, but more
      research is needed.

PMID- 22592702
TI  - Acupuncture for treatment of irritable bowel syndrome.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a common, costly, and difficult to
      treat disorder that impairs health-related quality of life and work productivity.
      Evidence-based treatment guidelines have been unable to provide guidance on the
      effects of acupuncture for IBS because the only previous systematic review
      included only small, heterogeneous and methodologically unsound trials.
      OBJECTIVES: The primary objectives were to assess the efficacy and safety of
      acupuncture for treating IBS. SEARCH METHODS: MEDLINE, the Cochrane Central
      Register of Controlled Trials, EMBASE, the Cumulative Index to Nursing and Allied
      Health, and the Chinese databases Sino-Med, CNKI, and VIP were searched through
      November 2011. SELECTION CRITERIA: Randomized controlled trials (RCTs) that
      compared acupuncture with sham acupuncture, other active treatments, or no
      (specific) treatment, and RCTs that evaluated acupuncture as an adjuvant to
      another treatment, in adults with IBS were included. DATA COLLECTION AND
      ANALYSIS: Two authors independently assessed the risk of bias and extracted data.
      We extracted data for the outcomes overall IBS symptom severity and health
      related quality of life. For dichotomous data (e.g. the IBS Adequate Relief
      Question), we calculated a pooled relative risk (RR) and 95% confidence interval
      (CI) for substantial improvement in symptom severity after treatment. For
      continuous data (e.g. the IBS Severity Scoring System), we calculated the
      standardized mean difference (SMD) and 95% CI in post-treatment scores between
      groups. MAIN RESULTS: Seventeen RCTs (1806 participants) were included. Five RCTs
      compared acupuncture versus sham acupuncture. The risk of bias in these studies
      was low. We found no evidence of an improvement with acupuncture relative to sham
      (placebo) acupuncture for symptom severity (SMD -0.11, 95% CI -0.35 to 0.13; 4
      RCTs; 281 patients) or quality of life (SMD = -0.03, 95% CI -0.27 to 0.22; 3
      RCTs; 253 patients). Sensitivity analyses based on study quality did not change
      the results. A GRADE analysis indicated that the overall quality of the evidence
      for the primary outcomes in the sham controlled trials was moderate due to sparse
      data. The risk of bias in the four Chinese language comparative effectiveness
      trials that compared acupuncture with drug treatment was high due to lack of
      blinding. The risk of bias in the other studies that did not use a sham control
      was high due to lack of blinding or inadequate methods used for randomization and
      allocation concealment or both. Acupuncture was significantly more effective than
      pharmacological therapy and no specific treatment. Eighty-four per cent of
      patients in the acupuncture group had improvement in symptom severity compared to
      63% of patients in the pharmacological treatment group (RR 1.28, 95% CI 1.12 to
      1.45; 5 studies, 449 patients). A GRADE analysis indicated that the overall
      quality of the evidence for this outcome was low due to a high risk of bias (no
      blinding) and sparse data. Sixty-three per cent of patients in the acupuncture
      group had improvement in symptom severity compared to 34% of patients in the no
      specific therapy group (RR 2.11, 95% CI 1.18 to 3.79; 2 studies, 181 patients).
      There was no statistically significant difference between acupuncture and
      Bifidobacterium (RR 1.07, 95% CI 0.90 to 1.27; 2 studies; 181 patients) or
      between acupuncture and psychotherapy (RR 1.05, 95% CI 0.87 to 1.26; 1 study; 100
      patients). Acupuncture as an adjuvant to another Chinese medicine treatment was
      significantly better than the other treatment alone. Ninety-three per cent of
      patients in the adjuvant acupuncture group improved compared to 79% of patients
      who received Chinese medicine alone (RR 1.17, 95% CI 1.02 to 1.33; 4 studies; 466
      patients). There was one adverse event (i.e. acupuncture syncope) associated with
      acupuncture in the 9 trials that reported this outcome, although relatively small
      sample sizes limit the usefulness of these safety data. AUTHORS' CONCLUSIONS:
      Sham-controlled RCTs have found no benefits of acupuncture relative to a credible
      sham acupuncture control for IBS symptom severity or IBS-related quality of life.
      In comparative effectiveness Chinese trials, patients reported greater benefits
      from acupuncture than from two antispasmodic drugs (pinaverium bromide and
      trimebutine maleate), both of which have been shown to provide a modest benefit
      for IBS. Future trials may help clarify whether or not these reportedly greater
      benefits of acupuncture relative to pharmacological therapies are due entirely to
      patients' preferences for acupuncture or greater expectations of improvement on
      acupuncture relative to drug therapy.

PMID- 22592703
TI  - Interventions for non-oliguric hyperkalaemia in preterm neonates.
AB  - BACKGROUND: Non-oliguric hyperkalaemia of the newborn is defined as a plasma
      potassium level > 6.5 mmol/L in the absence of acute renal failure. Hyperkalaemia
      is a common complication in the first 48 hours of life in very low birth weight
      (VLBW) (birth weight < 1500 g) and/or very preterm newborns (<=32 weeks
      gestational age). OBJECTIVES: To determine the effectiveness and safety of
      interventions for non-oliguric hyperkalaemia [for the purpose of this review
      defined as serum potassium > 6.0 mmol/L (the clinical setting in which
      interventions would likely be introduced prior to reaching a grossly abnormal
      level) and urine output > 0.5 ml/kg/hour] in preterm or VLBW infants during their
      first 72 hours of life. SEARCH METHODS: The Cochrane Central Register of
      Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2006) was searched to
      identify relevant randomised and quasi-randomised controlled trials. The
      following data bases were searched in June 2006; MEDLINE from 1966, EMBASE from
      1980, CINAHL from 1982. Search updated in June 2011. SELECTION CRITERIA:
      Randomised or quasi-randomised controlled trials conducted in preterm and/or VLBW
      neonates with a diagnosis of non-oliguric hyperkalaemia. Interventions included
      were those aimed at redistributing serum potassium (sodium bicarbonate or insulin
      and glucose) or increasing the elimination of potassium from the body [diuretics
      (any type) or ion exchange resins (any type), or exchange transfusion, or
      peritoneal dialysis, or salbutamol, or albuterol] or counteracting potential
      arrhythmias from hyperkalaemia (calcium) versus placebo or no intervention; or
      comparing any two of these interventions. Primary outcome measure was 'All cause
      mortality during initial hospital stay'. Secondary outcomes included common
      adverse outcomes seen in preterm infants. DATA COLLECTION AND ANALYSIS: We used
      the standard review methods of the Cochrane Neonatal Review Group. Two authors
      assessed all studies identified as potentially relevant by the literature search
      for inclusion in the review. Statistical methods included relative risk (RR),
      risk difference (RD), number needed to treat to benefit (NNTB) or number needed
      to treat to harm (NNTH) for dichotomous and weighted mean difference (WMD) for
      continuous outcomes reported with 95% confidence intervals (CI). We used a fixed
      effect model for meta-analysis. Heterogeneity was assessed using the I squared
      (I(2) ) statistic. MAIN RESULTS: Three randomised trials, enrolling 74 preterm
      infants (outcome data available on 71 infants) evaluated interventions for
      hyperkalaemia. Urine output was ascertained in only one study (Hu 1999). In none
      of the trials could we ascertain that allocation to the comparison groups was
      concealed. The sample sizes of the three trials were very small with 12 (Malone
      1991), 19 (Singh 2002) and 40 infants enrolled (Hu 1999). The intervention and
      the outcome assessments could not be blinded to the clinical staff in two trials
      (Malone 1991; Hu 1999).One study (Malone 1991), glucose and insulin, compared to
      cation-exchange resin, caused a reduction in all cause mortality that was of
      borderline statistical significance: RR 0.18 (95% CI 0.03 to 1.15); RD -0.66 (95%
      CI -1.09 to -0.22); NNTB 2 (95% CI 1 to 5)]. In the study of Hu (Hu 1999), the
      incidence of intraventricular haemorrhage >= grade 2 was significantly reduced
      [RR 0.30 (95% CI 0.10 to 0.93); RD -0.35 (95% CI -0.62 to -0.08); NNTB 3 (95% CI
      2 to 13).Albuterol inhalation versus saline inhalation changed serum K+ from
      baseline at four hours [WMD -0.69 mmol/L (95% CI -0.87 to -0.51)] and at eight
      hours [WMD -0.59 mmol/L (95% CI -0.78 to -0.40)] after initiation of treatment.
      No differences noted in mortality or other clinical outcomes (Singh 2002).No
      serious side effects were noted with either the combination of insulin and
      glucose or albuterol inhalation. Other interventions listed in our objectives
      have not been studied to date. AUTHORS' CONCLUSIONS: In view of the limited
      information from small studies of uncertain quality, no firm recommendations for
      clinical practice can be made. It appears that the combination of insulin and
      glucose is preferred over treatment with rectal cation-resin for hyperkalaemia in
      preterm infants. Both the combination of insulin and glucose and albuterol
      inhalation deserve further study. The two interventions could possibly be tested
      against each other. The effectiveness of other potentially effective
      interventions for non-oliguric hyperkalaemia (diuretics, exchange transfusion,
      peritoneal dialysis and calcium) have not been tested in randomised controlled
      trials.

PMID- 22592704
TI  - Recompression and adjunctive therapy for decompression illness.
AB  - BACKGROUND: Decompression illness (DCI) is due to bubble formation in the blood
      or tissues following the breathing of compressed gas. Clinically, DCI may range
      from a trivial illness to loss of consciousness, death or paralysis.
      Recompression is the universally accepted standard treatment of DCI. When
      recompression is delayed, a number of strategies have been suggested in order to
      improve the outcome. OBJECTIVES: To examine the effectiveness and safety of both
      recompression and adjunctive therapies in the treatment of DCI. SEARCH METHODS:
      In our previous update we searched until October 2009. In this version we
      searched CENTRAL (The Cochrane Library, October 2011); MEDLINE (1966 to October
      2011); CINAHL (1982 to October 2011); EMBASE (1980 to October 2011); the Database
      of Randomised Controlled Trials in Hyperbaric Medicine (October 2011); and
      handsearched journals and texts. SELECTION CRITERIA: We included randomized
      controlled trials that compared the effect of any recompression schedule or
      adjunctive therapy with a standard recompression schedule. We did not apply
      language restrictions. DATA COLLECTION AND ANALYSIS: Three authors extracted the
      data independently. We assessed each trial for internal validity and resolved
      differences by discussion. Data were entered into RevMan 5.1. MAIN RESULTS: Two
      randomized controlled trials enrolling a total of 268 patients satisfied the
      inclusion criteria. The risk of bias for Drewry 1994 was unclear as this study
      was presented as an abstract, while Bennett 2003 was rated as at low risk.
      Pooling of data was not possible. In one study there was no evidence of improved
      effectiveness with the addition of a non-steroidal anti-inflammatory drug
      (tenoxicam) to routine recompression therapy (at six weeks: relative risk (RR)
      1.04, 95% confidence interval (CI) 0.90 to 1.20, P = 0.58) but there was a
      reduction in the number of compressions required when tenoxicam was added from
      three to two (P = 0.01, 95% CI 0 to 1). In the other study, the odds of multiple
      recompressions were lower with a helium and oxygen (heliox) table compared to an
      oxygen treatment table (RR 0.56, 95% CI 0.31 to 1.00, P = 0.05). AUTHORS'
      CONCLUSIONS: Recompression therapy is standard for the treatment of DCI, but
      there is no randomized controlled trial evidence for its use. Both the addition
      of a non-steroidal anti-inflammatory drug (NSAID) and the use of heliox may
      reduce the number of recompressions required, but neither improve the odds of
      recovery. The application of either of these strategies may be justified. The
      modest number of patients studied demands a cautious interpretation. Benefits may
      be largely economic and an economic analysis should be undertaken. There is a
      case for large randomized trials of high methodological rigour in order to define
      any benefit from the use of different breathing gases and pressure profiles
      during recompression therapy.

PMID- 22592705
TI  - Metal protein attenuating compounds for the treatment of Alzheimer's dementia.
AB  - BACKGROUND: Alzheimer's dementia (AD) may be caused by the formation of
      extracellular senile plaques comprised of beta-amyloid (Abeta). In vitro and
      mouse model studies have demonstrated that metal protein attenuating compounds
      (MPACs) promote the solubilisation and clearance of Abeta. OBJECTIVES: To
      evaluate the efficacy of metal protein attenuating compounds (MPACs) for the
      treatment of cognitive impairment due to Alzheimer's dementia. SEARCH METHODS: We
      searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group Specialized
      Register, on 29 July 2010 using the terms: Clioquinol OR PBT1 OR PBT2 OR "metal
      protein" OR MPACS OR MPAC. SELECTION CRITERIA: Randomised double-blind trials in
      which treatment with an MPAC was administered to participants with Alzheimer's
      dementia in a parallel group comparison with placebo were included. DATA
      COLLECTION AND ANALYSIS: Three review authors (RM, LJ, ELS) independently
      assessed the quality of trials according to the Cochrane Handbook for Systematic
      Reviews of Interventions.The primary outcome measure of interest was cognitive
      function (as measured by psychometric tests). The secondary outcome measures of
      interest were in the following areas: quality of life, functional performance,
      effect on carer, biomarkers, safety and adverse effects, and death. MAIN RESULTS:
      Two MPAC trials were identified. One trial compared clioquinol (PBT1) with
      placebo in 36 patients and 32 had sufficient data for per protocol analysis.
      There was no statistically significant difference in cognition (as measured on
      the Alzheimer's Disease Assessment Scale - Cognition (ADAS-Cog)) between the
      active treatment and placebo groups at 36 weeks. The difference in mean change
      from baseline ADAS-Cog score in the clioquinol arm compared with the placebo arm
      at weeks 24 and 36 was a difference of 7.37 (95% confidence interval (CI) 1.51 to
      13.24) and 6.36 (95% CI -0.50 to 13.23), respectively.There was no significant
      impact on non-cognitive symptoms or clinical global impression. One participant
      in the active treatment group developed neurological symptoms (impaired visual
      acuity and colour vision) which resolved on cessation of treatment and were
      possibly attributable to the drug.In the second trial a successor compound, PBT2,
      was compared with placebo in 78 participants with mild Alzheimer's dementia; all
      were included in the intention-to-treat analysis. There was no significant
      difference in the Neuropsychological Test Battery (NTB) composite, memory or
      executive scores between placebo and PBT2 in the least squares mean change from
      baseline at week 12. However, two executive function component tests of the NTB
      showed significant improvement over placebo in the PBT2 250 mg group from
      baseline to week 12: category fluency test (2.8 words, 95% CI 0.1 to 5.4; P =
      0.041) and trail making part B (-48.0 s, 95% CI -83.0 to -13.0; P = 0.009). There
      was no significant effect on cognition on Mini-Mental State Examination (MMSE) or
      ADAS-Cog scales. PBT2 had a favourable safety profile. AUTHORS' CONCLUSIONS:
      There is an absence of evidence as to whether clioquinol (PBT1) has any positive
      clinical benefit for patients with AD, or whether the drug is safe. We have some
      concerns about the quality of the study methodology; there was an imbalance in
      treatment and control groups after randomisation (participants in the active
      treatment group had a higher mean pre-morbid IQ) and the secondary analyses of
      results stratified by baseline dementia severity. The planned phase III trial of
      PBT1 has been abandoned and this compound has been withdrawn from development.
      The second trial of PBT2 was more rigorously conducted and showed that after 12
      weeks this compound appeared to be safe and well tolerated in people with mild
      Alzheimer's dementia. Larger trials are now required to demonstrate cognitive
      efficacy.

PMID- 22592707
TI  - Extracorporeal shock wave lithotripsy (ESWL) versus ureteroscopic management for
      ureteric calculi.
AB  - BACKGROUND: Ureteral stones frequently cause renal colic, and if left untreated,
      can lead to obstructive uropathy. Extracorporeal shock wave lithotripsy (ESWL)
      and ureteroscopy, with or without intracorporeal lithotripsy, are the most common
      interventions used to treat ureteral stones. ESWL treatment is less invasive than
      ureteroscopy, but has some limitations such as a high retreatment rate, and is
      not available in all centres. Recent advances in ureteroscopy have increased
      success rates and reduced complication rates. OBJECTIVES: To examine evidence
      from randomised controlled trials (RCTs) on the outcomes of ESWL or ureteroscopy
      in the treatment of ureteric calculi. SEARCH METHODS: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL in The Cochrane Library Issue 2,
      2011), MEDLINE (1966 to March 2011), EMBASE (1980 to March 2011), CINAHL,
      Clinicaltrials.gov, Google Scholar, reference lists of articles and abstracts
      from conference proceedings, all without language restriction. SELECTION
      CRITERIA: RCTs that compared ESWL with ureteroscopic retrieval of ureteric stones
      were included in this review. Study participants were adults with ureteric stones
      requiring intervention. Published and unpublished sources were considered for
      inclusion. DATA COLLECTION AND ANALYSIS: Three authors independently assessed
      study quality, risk of bias, and extracted data. Statistical analyses were
      performed using the random-effects model. Results were expressed as risk ratios
      (RR) for dichotomous outcomes or mean differences (MD) for continuous data, both
      with 95% confidence intervals (CI). MAIN RESULTS: Seven RCTs (1205 patients) were
      included in the review. Stone-free rates were lower in patients who underwent
      ESWL (7 studies, 1205 participants: RR 0.84, 95% CI 0.73 to 0.96) but re
      treatment rates were lower in ureteroscopy patients (6 studies, 1049
      participants: RR 6.18, 95% CI 3.68 to 10.38. ESWL-treated patients had less need
      for auxiliary treatment (5 studies, 751 participants: RR 0.43, 95% CI 0.25 to
      0.74; fewer complications (7 studies, 1205 participants: RR 0.54, 95% CI 0.33 to
      0.88); and shorter length of hospital stay (2 studies, 198 participants: MD -2.55
      days, 95% CI -3.24 to -1.86).Three studies adequately described the randomisation
      sequence, three studies were unclear on how they randomised, while one study had
      a high risk of selection bias. All the studies had an unclear risk of performance
      bias and detection bias, while all had a low risk of attrition bias, reporting
      bias, or other sources of bias identified. AUTHORS' CONCLUSIONS: Compared with
      ESWL, ureteroscopic removal of ureteral stones achieves a greater stone-free
      state, but with a higher complication rate and longer hospital stay.

PMID- 22592708
TI  - Leukotriene receptor antagonists in addition to usual care for acute asthma in
      adults and children.
AB  - BACKGROUND: Acute asthma presentation in the emergency setting frequently leads
      to hospital admission. Currently available treatment options include
      corticosteroid therapy, beta(2)-agonists and oxygen. Antileukotriene agents are
      beneficial in chronic asthma as additional therapy to inhaled steroids. Their
      value when used orally or intravenously in the acute setting requires evaluation.
      OBJECTIVES: To determine if the addition of a leukotriene receptor antagonist
      (LTRA) produces a beneficial effect in children and adults with acute asthma who
      are currently receiving inhaled bronchodilators and systemic corticosteroids.
      SEARCH METHODS: We searched the Cochrane Airways Group's Specialised Register of
      trials with predefined terms. Searches are current to February 2012. SELECTION
      CRITERIA: We included randomised trials comparing antileukotrienes and standard
      acute asthma care versus placebo and standard care in people with acute asthma of
      any age. We considered any dose and method of delivery of the leukotriene agent.
      DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for
      inclusion in the review and extracted data. We then checked data and resolved
      disagreements by discussion. We contacted study authors where necessary to
      provide additional information and data. MAIN RESULTS: Eight trials, generating
      10 treatment-control comparisons, that recruited 1470 adults and 470 children met
      the entry criteria. These studies were of mixed quality, and there was
      heterogeneity in the severity of asthma exacerbation.For oral treatment, there
      was no significant difference in hospital admission between LTRAs and control in
      three trials on 194 children (risk ratio (RR) 0.86; 95% confidence interval (CI)
      0.21 to 3.52). Using a broader composite outcome which measured requirement for
      additional care there was no significant difference between treatments (RR 0.87;
      95% CI 0.60 to 1.28). Results demonstrated some indication of improvement in lung
      function with a significant difference in forced expiratory volume in one second
      (FEV(1)) favouring LTRAs in two trials on 641 adults (mean difference (MD) 0.08;
      95% CI 0.01 to 0.14). There were insufficient data to assess this outcome in
      children. The most common adverse event described was headache; however, there
      was no significant difference between LTRAs and control (RR 0.81; 95% CI 0.22 to
      2.99). Due to insufficient numbers, we were unable to conduct a subgroup analysis
      based on age.The combined results of two trials of intravenous treatment in 772
      adults and one trial in 276 children demonstrated a reduction in the risk of
      hospital admission which was not quite statistically significant (RR 0.78; 95% CI
      0.61 to 1.01). There was a statistically significant small difference in FEV(1)
      in the adult studies (MD 0.12; 95% CI 0.06 to 0.17), but not in the single trial
      in children (MD 0.01; 95% CI -0.06 to 0.08). AUTHORS' CONCLUSIONS: Presently, the
      available evidence does not support routine use of oral LTRAs in acute asthma.
      Further studies are required to assess whether intravenous treatment can reduce
      the risk of hospital admission, and what the most appropriate dose regimen is.
      Additional research is also needed into safety and efficacy of additional doses
      for those on maintenance therapy, and larger paediatric trials are required to
      allow subgroup analysis. Prolonged studies would be required to establish other
      health economic outcomes in admitted patients.

PMID- 22592706
TI  - Interventions for chronic blepharitis.
AB  - BACKGROUND: Blepharitis, an inflammatory condition associated with itchiness,
      redness, flaking, and crusting of the eyelids, is a common eye condition that
      affects both children and adults. It is common in all ethnic groups and across
      all ages. Although infrequent, blepharitis can lead to permanent alterations to
      the eyelid margin or vision loss from superficial keratopathy (abnormality of the
      cornea), corneal neovascularization, and ulceration. Most importantly,
      blepharitis frequently causes significant ocular symptoms such as burning
      sensation, irritation, tearing, and red eyes as well as visual problems such as
      photophobia and blurred vision. The exact etiopathogenesis is unknown, but
      suspected to be multifactorial, including chronic low-grade infections of the
      ocular surface with bacteria, infestations with certain parasites such as
      demodex, and inflammatory skin conditions such as atopy and seborrhea.
      Blepharitis can be categorized in several different ways. First, categorization
      is based on the length of disease process: acute or chronic blepharitis. Second,
      categorization is based on the anatomical location of disease: anterior, or front
      of the eye (e.g. staphylococcal and seborrheic blepharitis), and posterior, or
      back of the eye (e.g. meibomian gland dysfunction (MGD)). This review focuses on
      chronic blepharitis and stratifies anterior and posterior blepharitis.
      OBJECTIVES: To examine the effectiveness of interventions in the treatment of
      chronic blepharitis. SEARCH METHODS: We searched CENTRAL (which contains the
      Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue
      1), MEDLINE (January 1950 to February 2012), EMBASE (January 1980 to February
      2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com),
      ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical
      Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We searched the
      reference lists of included studies for any additional studies not identified by
      the electronic searches. There were no date or language restrictions in the
      electronic searches for trials. The electronic databases were last searched on 9
      February 2012. SELECTION CRITERIA: We included randomized controlled trials
      (RCTs) and quasi-randomized controlled trials (CCTs) in which participants were
      adults aged 16 years or older and clinically diagnosed with chronic blepharitis.
      We also included trials where participants with chronic blepharitis were a subset
      of the participants included in the study and data were reported separately for
      these participants. Interventions within the scope of this review included
      medical treatment and lid hygiene measures. DATA COLLECTION AND ANALYSIS: Two
      authors independently assessed search results, reviewed full-text copies for
      eligibility, examined risk of bias, and extracted data. Data were meta-analyzed
      for studies comparing similar interventions and reporting comparable outcomes
      with the same timing. Otherwise, results for included studies were summarized in
      the text. MAIN RESULTS: There were 34 studies (2169 participants with
      blepharitis) included in this review: 20 studies (14 RCTs and 6 CCTs) included
      1661 participants with anterior or mixed blepharitis and 14 studies (12 RCTs and
      2 CCTs) included 508 participants with posterior blepharitis (MGD). Due to the
      heterogeneity of study characteristics among the included studies, with respect
      to follow-up periods and types of interventions, comparisons, and condition of
      participants, our ability to perform meta-analyses was limited. Topical
      antibiotics were shown to provide some symptomatic relief and were effective in
      eradicating bacteria from the eyelid margin for anterior blepharitis. Lid hygiene
      may provide symptomatic relief for anterior and posterior blepharitis. The
      effectiveness of other treatments for blepharitis, such as topical steroids and
      oral antibiotics, were inconclusive. AUTHORS' CONCLUSIONS: Despite identifying 34
      trials related to treatments for blepharitis, there is no strong evidence for any
      of the treatments in terms of curing chronic blepharitis. Commercial products are
      marketed to consumers and prescribed to patients without substantial evidence of
      effectiveness. Further research is needed to evaluate the effectiveness of such
      treatments. Any RCT designed for this purpose should separate participants by
      type of condition (e.g. staphylococcal blepharitis or MGD) in order to minimize
      imbalances between groups (type I errors) and to achieve statistical power for
      analyses (prevent type II errors). Medical interventions and commercial products
      should be compared with conventional lid hygiene measures, such as warm
      compresses and eyelid margin washing, to determine effectiveness, as well as head
      to-head to show comparative effectiveness between treatments. Outcomes of
      interest should be patient-centered and measured using validated questionnaires
      or scales. It is important that participants be followed long-term, at least one
      year, to assess chronic outcomes properly.

PMID- 22592709
TI  - Home uterine monitoring for detecting preterm labour.
AB  - BACKGROUND: To reduce the morbidity and mortality associated with preterm birth,
      home uterine activity monitoring aims for early detection of increased
      contraction frequency, and early intervention with tocolytic drugs to inhibit
      labour and prolong pregnancy. However, the effectiveness of such monitoring is
      disputed. OBJECTIVES: To determine whether home uterine activity monitoring is
      effective in improving the outcomes for women and their infants considered to be
      at high risk of preterm birth, when compared with conventional or other care
      packages that do not include home uterine monitoring. SEARCH METHODS: We searched
      the Cochrane Pregnancy and Childbirth Group's Trials Register (30 November 2011),
      CENTRAL (The Cochrane Library 2011, Issue 4 of 4), MEDLINE (1966 to 30 November
      2011), EMBASE (1974 to 30 November 2011), CINAHL (1982 to 30 November 2011) and
      scanned reference lists of retrieved studies. SELECTION CRITERIA: Randomised
      control trials of home uterine activity monitoring, with or without patient
      education programmes, for women at risk for preterm birth, in comparison to the
      same care package without home uterine activity monitoring. DATA COLLECTION AND
      ANALYSIS: Two review authors independently assessed trials for inclusion,
      extracted data and assessed risk of bias. Data were checked for accuracy. We did
      not attempt to contact authors to resolve queries. MAIN RESULTS: There were 15
      included studies (total number of enrolled participants 6008); 13 studies
      contributed data. Women using home uterine monitoring were less likely to
      experience preterm birth at less than 34 weeks (risk ratio (RR) 0.78; 95%
      confidence interval (CI) 0.62 to 0.99; three studies, n = 1596; fixed-effect
      analysis). However, this significant difference was not evident when we carried
      out a sensitivity analysis, restricting the analysis to studies at low risk of
      bias based on study quality (RR 0.75; 95% CI 0.57 to 1.00, one study, 1292
      women). There was no significant difference in the rate of perinatal mortality
      (RR 1.22; 95% CI 0.86 to 1.72; two studies, n = 2589).There was no significant
      difference in the number of preterm births at less than 37 weeks (average RR
      0.85; CI 0.72 to 1.01; eight studies, n = 4834; random effects, T(2) = 0.03, I(2)
      = 68%). Infants born to women using home uterine monitoring were less likely to
      be admitted to neonatal intensive care unit (average RR 0.77; 95% CI 0.62 to
      0.96; five studies, n = 2367; random-effects, T(2) = 0.02, I(2) = 32%). Although
      this difference was not statistically significant when only high quality studies
      were included (RR 0.86; 95% CI 0.74 to 1.01; one study, n = 1292). Women using
      home uterine monitoring made more unscheduled antenatal visits (mean difference
      (MD) 0.49; 95% CI 0.39 to 0.62; two studies, n = 2807). Women using home uterine
      monitoring were also more likely to have prophylactic tocolytic drug therapy
      (average RR 1.21; 95% CI 1.01 to 1.45; seven studies, n = 4316; random-effects.
      T(2) = 0.03, I(2) = 62%) but this difference was no longer significant when the
      analysis was restricted to high quality studies (average RR 1.22; 95% CI 0.90 to
      1.65, three studies, n = 3749,random effects, T(2) = 0.05, I(2) = 76%). One small
      study reported that the home uterine monitoring group spent fewer days in
      hospital antenatally. No data on maternal anxiety or acceptability were found.
      AUTHORS' CONCLUSIONS: Home uterine monitoring may result in fewer admissions to a
      neonatal intensive care unit but more unscheduled antenatal visits and tocolytic
      treatment. There is no impact on maternal and perinatal outcomes such as
      perinatal mortality or incidence of preterm birth.

PMID- 22592710
TI  - Local cooling for relieving pain from perineal trauma sustained during
      childbirth.
AB  - BACKGROUND: Perineal trauma is common during childbirth and may be painful.
      Contemporary maternity practice includes offering women numerous forms of pain
      relief, including the local application of cooling treatments. OBJECTIVES: To
      evaluate the effectiveness and side effects of localised cooling treatments
      compared with no treatment, other forms of cooling treatments and non-cooling
      treatments. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth
      Group's Trials Register (10 January 2012), CINAHL (1982 to 10 January 2012), the
      Australian New Zealand Clinical Trials Register (10 January 2012) and contacted
      experts in the field. SELECTION CRITERIA: Published and unpublished randomised
      and quasi-randomised trials (RCTs) that compared localised cooling treatment
      applied to the perineum with no treatment or other treatments applied to relieve
      pain related to perineal trauma sustained during childbirth. DATA COLLECTION AND
      ANALYSIS: At least two review authors independently assessed trials for
      inclusion, assessed trial quality and extracted data. A sub-set of data were
      double checked for accuracy. Analyses were performed on an intention-to-treat
      basis where data allowed. We sought additional information from the authors of
      three trials. MAIN RESULTS: Ten published RCTs were included (involving 1825
      women). Comparisons were local cooling treatments (ice packs, cold gel pads (with
      or without compression) or cold/iced baths) with no treatment, gel pads with
      compression, hamamelis water (witch hazel), pulsed electromagnetic energy (PET),
      hydrocortisone/pramoxine foam (Epifoam), oral paracetamol or warm baths. Ice
      packs provided improved pain relief 24 to 72 hours after birth compared with no
      treatment (risk ratio (RR) 0.61; 95% confidence interval (CI) 0.41 to 0.91; one
      study, n = 208). Women preferred the utility of the gel pads compared with ice
      packs or no treatment (RR 0.82; 95% CI 0.73, 0.92). Differences detected in a
      composite of perineal oedema and bruising and overall wound healing were noted in
      one small study, favouring cold gel pads (n = 37) over ice (n = 35, mean
      difference (MD) 0.63 on a scale of 0 to 15; 95% CI 0.20 to 1.06) or no treatment
      (n = 39, MD -2.10; 95% CI -3.80 to -0.40) three to 14 days after giving birth.
      Women reported more pain (RR 5.60; 95% CI 2.35 to 13.33; one study, 100 women)
      and used more additional analgesia (RR 4.00; 95% CI 1.44 to 11.13; one study, 100
      women) following the application of ice packs compared with PET. AUTHORS'
      CONCLUSIONS: There is only limited evidence to support the effectiveness of local
      cooling treatments (ice packs, cold gel pads, cold/iced baths) applied to the
      perineum following childbirth to relieve pain.

PMID- 22592711
TI  - Rapid viral diagnosis for acute febrile respiratory illness in children in the
      Emergency Department.
AB  - BACKGROUND: Pediatric acute respiratory infections (ARIs) represent a significant
      burden on pediatric Emergency Departments (EDs) and families. Most of these
      illnesses are due to viruses. However, investigations (radiography, blood, and
      urine testing) to rule out bacterial infections and antibiotics are often ordered
      because of diagnostic uncertainties. This results in prolonged ED visits and
      unnecessary antibiotic use. The risk of concurrent bacterial infection has been
      reported to be negligible in children over three months of age with a confirmed
      viral infection. Rapid viral testing in the ED may alleviate the need for
      precautionary testing and antibiotic use. OBJECTIVES: To determine the effect of
      rapid viral testing in the ED on the rate of precautionary testing, antibiotic
      use, and length of ED visit. SEARCH METHODS: We searched the Cochrane Central
      register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 4);
      EMBASE (1988 to December 2011); MEDLINE Ovid (1950 to November week 4, 2011);
      MEDLINE In-Process & Other Non-Indexed Citations (8 December 2011); HealthStar
      (1966 to 2009); BIOSIS Previews (1969 to December 2011); CAB Abstracts (1973 to
      December 2011); CBCA Reference (1970 to 2007); and Proquest Dissertations and
      Theses (1861 to 2009). SELECTION CRITERIA: Randomized controlled trials (RCTs) of
      rapid viral testing for children with ARIs in the ED. DATA COLLECTION AND
      ANALYSIS: Two review authors used the inclusion criteria to select trials,
      evaluate their quality and extract data. We obtained missing data from trial
      authors. We expressed differences in rate of investigations and antibiotic use as
      risk ratios (RRs), and expressed difference in ED length of visits as mean
      differences (MDs), with 95% confidence intervals (CIs). MAIN RESULTS: We included
      four trials (three RCTs and one quazi-RCT), with 759 children in the rapid viral
      testing group and 829 in the control group. Three out of the four studies were
      comparable in terms of young age of participants, with one study increasing the
      age of inclusion up to five years of age. All studies included either fever or
      respiratory symptoms as inclusion criteria (two required both, one required fever
      or respiratory symptoms, and one required only fever). All studies were
      comparable in terms of exclusion criteria, intervention, and outcome data. In
      terms of risk of bias, one study failed to utilize a random sequence generator,
      one study did not comment on completeness of outcome data, and only one of four
      studies included allocation concealment as part of the study design. None of the
      studies definitively blinded participants.Rapid viral testing did not reduce
      antibiotic use in the ED significantly, neither clinically nor statistically. We
      found lower rates of chest radiography (RR 0.77, 95% CI 0.65 to 0.91) in the
      rapid viral testing group, but no effect on length of ED visits, or blood or
      urine testing in the ED. No study made mention of any adverse effects related to
      viral testing. AUTHORS' CONCLUSIONS: Current evidence is insufficient to support
      routine rapid viral testing as a means to reduce antibiotic use in pediatric EDs.
      Results suggest that rapid viral testing may be beneficial in terms of reducing
      rates of antibiotic usage, urine investigations and blood investigations, but are
      not statistically significant due to lack of power. Rapid viral testing does
      reduce the rate of chest X-rays in the ED. A large trial addressing the effect on
      antibiotic usage is needed.

PMID- 22592712
TI  - Chinese herbal medicine for endometriosis.
AB  - BACKGROUND: Endometriosis is characterized by the presence of tissue that is
      morphologically and biologically similar to normal endometrium in locations
      outside the uterus. Surgical and hormonal treatment of endometriosis have
      unpleasant side effects and high rates of relapse. In China, treatment of
      endometriosis using Chinese herbal medicine (CHM) is routine and considerable
      research into the role of CHM in alleviating pain, promoting fertility, and
      preventing relapse has taken place.This review is an update of a previous review
      published in the Cochrane Database of Systematic Reviews 2009, issue No 3.
      OBJECTIVES: To review the effectiveness and safety of CHM in alleviating
      endometriosis-related pain and infertility. SEARCH METHODS: We searched the
      Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central
      Register of Controlled Trials (CENTRAL) (The Cochrane Library) and the following
      English language electronic databases (from their inception to 31/10/2011):
      MEDLINE, EMBASE, AMED, CINAHL, and NLH.We also searched Chinese language
      electronic databases: Chinese Biomedical Literature Database (CBM), China
      National Knowledge Infrastructure (CNKI), Chinese Sci & Tech Journals (VIP),
      Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS),
      and Chinese Medical Current Contents (CMCC). SELECTION CRITERIA: Randomised
      controlled trials (RCTs) involving CHM versus placebo, biomedical treatment,
      another CHM intervention; or CHM plus biomedical treatment versus biomedical
      treatment were selected. Only trials with confirmed randomisation procedures and
      laparoscopic diagnosis of endometriosis were included. DATA COLLECTION AND
      ANALYSIS: Risk of bias assessment, and data extraction and analysis were
      performed independently by three review authors. Data were combined for meta
      analysis using relative risk (RR) for dichotomous data. A fixed-effect
      statistical model was used, where appropriate. Data not suitable for meta
      analysis were presented as descriptive data. MAIN RESULTS: Two Chinese RCTs
      involving 158 women were included in this review. Both these trials described
      adequate methodology. Neither trial compared CHM with placebo treatment.There was
      no evidence of a significant difference in rates of symptomatic relief between
      CHM and gestrinone administered subsequent to laparoscopic surgery (95.65% versus
      93.87%; risk ratio (RR) 1.02, 95% confidence interval (CI) 0.93 to 1.12, one
      RCT). The intention-to-treat analysis also showed no significant difference
      between the groups (RR 1.04, 95% CI 0.91 to 1.18). There was no significant
      difference between the CHM and gestrinone groups with regard to the total
      pregnancy rate (69.6% versus 59.1%; RR 1.18, 95% CI 0.87 to 1.59, one RCT).CHM
      administered orally and then in conjunction with a herbal enema resulted in a
      greater proportion of women obtaining symptomatic relief than with danazol (RR
      5.06, 95% CI 1.28 to 20.05; RR 5.63, 95% CI 1.47 to 21.54, respectively).
      Overall, 100% of women in all the groups showed some improvement in their
      symptoms.Oral plus enema administration of CHM showed a greater reduction in
      average dysmenorrhoea pain scores than did danazol (mean difference (MD) -2.90,
      95% CI -4.55 to -1.25; P < 0.01). Combined oral and enema administration of CHM
      also showed a greater improvement measured as the disappearance or shrinkage of
      adnexal masses than with danazol (RR 1.70, 95% CI 1.04 to 2.78). For lumbosacral
      pain, rectal discomfort, or vaginal nodules tenderness, there was no significant
      difference between CHM and danazol. AUTHORS' CONCLUSIONS: Post-surgical
      administration of CHM may have comparable benefits to gestrinone but with fewer
      side effects. Oral CHM may have a better overall treatment effect than danazol;
      it may be more effective in relieving dysmenorrhoea and shrinking adnexal masses
      when used in conjunction with a CHM enema. However, more rigorous research is
      required to accurately assess the potential role of CHM in treating
      endometriosis.

PMID- 22592713
TI  - Abdominal lift for laparoscopic cholecystectomy.
AB  - BACKGROUND: Laparoscopic cholecystectomy (key-hole removal of the gallbladder) is
      now the most often used method for treatment of symptomatic gallstones. Several
      cardiopulmonary changes (decreased cardiac output, pulmonary compliance, and
      increased peak airway pressure) occur during pneumoperitoneum, which is now
      introduced to allow laparoscopic cholecystectomy. These cardiopulmonary changes
      may not be tolerated in individuals with poor cardiopulmonary reserve.
      OBJECTIVES: To assess the benefits and harms of abdominal wall lift compared with
      pneumoperitoneum in patients undergoing laparoscopic cholecystectomy. SEARCH
      METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials
      Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The
      Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until
      January 2012. SELECTION CRITERIA: We included all randomised clinical trials
      comparing abdominal wall lift (with or without pneumoperitoneum) versus
      pneumoperitoneum. DATA COLLECTION AND ANALYSIS: We calculated the risk ratio
      (RR), rate ratio (RaR), or mean difference (MD) with 95% confidence intervals
      (CI) based on intention-to-treat analysis with both the fixed-effect and the
      random-effects models using RevMan software. MAIN RESULTS: For abdominal wall
      lift with pneumoperitoneum versus pneumoperitoneum, a total of 156 participants
      (all with low anaesthetic risk) who underwent elective laparoscopic
      cholecystectomy were randomised in six trials to abdominal wall lift with
      pneumoperitoneum (n = 65) versus pneumoperitoneum only (n = 66). One trial which
      included 25 patients did not state the number of patients in each group. All six
      trials had a high risk of bias. There was no mortality or conversion to open
      cholecystectomy in any of the patients in the trials that reported these
      outcomes. There was no significant difference in the rate of serious adverse
      events between the two groups (2 trials; 2/29 events (0.069 events per patient)
      versus 2/29 events (0.069 events per patient); rate ratio 1.00; 95% CI 0.17 to
      5.77). None of the trials reported quality of life, the proportion of patients
      discharged as day-patient laparoscopic cholecystectomies, or pain between four
      and eight hours after the operation. There was no significant difference in the
      operating time between the two groups (4 trials; 53 patients versus 54 patients;
      13.39 minutes longer (2.73 less to 29.51 longer) in the abdominal wall lift with
      pneumoperitoneum group and 100 minutes in the pneumoperitoneum group).For
      abdominal wall lift versus pneumoperitoneum, a total of 774 participants (the
      majority with low anaesthetic risk) who underwent elective laparoscopic
      cholecystectomy were randomised in 18 trials to abdominal wall lift without
      pneumoperitoneum (n = 332) versus pneumoperitoneum (n = 358). One trial which
      included 84 patients did not state the number of patients in each group. All the
      trials had a high risk of bias. There was no mortality in any of the trials that
      reported this outcome. There was no significant difference in the rate of serious
      adverse events between the two groups (6 trials; 5/172 events (weighted number of
      events per patient = 0.020 events) versus 2/171 events (0.012 events per
      patient); rate ratio 1.73; 95% CI 0.35 to 8.61). None of the trials reported
      quality of life or pain between four and eight hours after the operation. There
      was no significant difference in the proportion of patients who underwent
      conversion to open cholecystectomy (11 trials; 5/225 (weighted proportion 2.3%)
      versus 7/235 (3.0%); RR 0.76; 95% CI 0.26 to 2.21). The operating time was
      significantly longer in the abdominal wall lift group than the pneumoperitoneum
      group (16 trials; 6.87 minutes longer (4.74 to 9.00 longer) in the abdominal wall
      lift group; 75 minutes in the pneumoperitoneum group). There was no significant
      difference in the proportion of patients who were discharged as day-patient
      laparoscopic cholecystectomy patients (2 trials; 15/31 (weighted proportion
      48.5%) versus 9/31 (29%); RR 1.67; 95% CI 0.85 to 3.26). AUTHORS' CONCLUSIONS:
      Abdominal wall lift does not seem to offer an advantage over pneumoperitoneum in
      any of the patient-oriented outcomes for laparoscopic cholecystectomy in patients
      with low anaesthetic risk. It may increase costs by increasing the operating
      time. Hence it cannot be recommended routinely. The safety of abdominal wall lift
      is yet to be established. More research on the topic is needed because of the
      risk of bias in the included trials and because of the risk of type I and type II
      random errors because of the few patients included in the trials. Such trials
      ought to include patients at higher anaesthetic risk. Furthermore, such trials
      ought to include blinded assessment of outcome measures.

PMID- 22592714
TI  - Patient education and counselling for promoting adherence to treatment for
      tuberculosis.
AB  - BACKGROUND: Non-adherence to tuberculosis treatment can lead to prolonged periods
      of infectiousness, relapse, emergence of drug-resistance, and increased morbidity
      and mortality. In this review, we assess whether patient education or
      counselling, or both, promotes adherence to tuberculosis treatment. OBJECTIVES:
      To evaluate the effects of patient education or counselling, or both, on
      treatment completion and cure in people requiring treatment for active or latent
      tuberculosis. SEARCH METHODS: Without language restriction, we searched for
      eligible studies in the Cochrane Infectious Diseases Group Specialized Register,
      Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and LILACS;
      checked reference lists of relevant articles; and contacted relevant researchers
      and organizations up to 24 November 2011. SELECTION CRITERIA: Randomized
      controlled trials examining the effects of education or counselling, or both, on
      treatment completion and cure in people with clinical tuberculosis; and treatment
      completion and clinical tuberculosis in people with latent disease. DATA
      COLLECTION AND ANALYSIS: We independently screened identified studies for
      eligibility, assessed methodological quality, and extracted data; with
      differences resolved by consensus. We expressed study results as risk ratios
      (RRs) with 95% confidence intervals (CI). MAIN RESULTS: We found three trials,
      with a total of 1437 participants, which examined the effects of different
      educational and counselling interventions on adherence to treatment for latent
      tuberculosis.All three trials reported the proportion of people who successfully
      completed treatment for latent tuberculosis. Overall, education or counselling
      interventions may increase successful treatment completion but the magnitude of
      benefit is likely to vary depending on the nature of the intervention, and the
      setting (data not pooled, 923 participants, three trials, low quality
      evidence).In a four-arm trial in children from Spain, counselling by nurses via
      telephone increased the proportion of children completing treatment from 65% to
      94% (RR 1.44, 95% CI 1.21 to 1.72; 157 participants, one trial), and counselling
      by nurses through home visits increased completion to 95% (RR 1.46, 95% CI 1.23
      to 1.74; 156 participants, one trial). Both of these interventions were superior
      to counselling by physicians at the tuberculosis clinic (RR 1.20, 95% CI 0.98 to
      1.47; 159 participants, one trial).In the USA, a programme of peer counselling
      for adolescents failed to show an effect on treatment completion rates at six
      months (RR 1.01, 95% CI 0.90 to 1.13; 394 participants, one trial). In this trial
      treatment completion was around 75% even in the control group.In the third study,
      in prisoners from the USA, treatment completion was very low in the control group
      (12%), and although counselling significantly improved this, completion in the
      intervention group remained low at 24% (RR 1.94, 95% CI 1.03 to 3.68; 211
      participants, one trial).None of these trials aimed to assess the effect of these
      interventions on the subsequent development of active tuberculosis, and we found
      no trials that assessed the effects of patient education or counselling on
      adherence to treatment for active tuberculosis. AUTHORS' CONCLUSIONS: Educational
      or counselling interventions may improve completion of treatment for latent
      tuberculosis. As would be expected, the magnitude of the benefit is likely to
      depend on the nature of the intervention, and the reasons for low completion
      rates in the specific setting.

PMID- 22592715
TI  - Home-based therapy programmes for upper limb functional recovery following
      stroke.
AB  - BACKGROUND: With an increased focus on home-based stroke services and the
      undertaking of programmes, targeted at upper limb recovery within clinical
      practice, a systematic review of home-based therapy programmes for individuals
      with upper limb impairment following stroke was required. OBJECTIVES: To
      determine the effects of home-based therapy programmes for upper limb recovery in
      patients with upper limb impairment following stroke. SEARCH METHODS: We searched
      the Cochrane Stroke Group's Specialised Trials Register (May 2011), the Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue
      2), MEDLINE (1950 to May 2011), EMBASE (1980 to May 2011), AMED (1985 to May
      2011) and six additional databases. We also searched reference lists and trials
      registers. SELECTION CRITERIA: Randomised controlled trials (RCTs) in adults
      after stroke, where the intervention was a home-based therapy programme targeted
      at the upper limb, compared with placebo, or no intervention or usual care.
      PRIMARY OUTCOMES were performance in activities of daily living (ADL) and
      functional movement of the upper limb. SECONDARY OUTCOMES were performance in
      extended ADL and motor impairment of the arm. DATA COLLECTION AND ANALYSIS: Two
      review authors independently screened abstracts, extracted data and appraised
      trials. We undertook assessment of risk of bias in terms of method of
      randomisation and allocation concealment (selection bias), blinding of outcome
      assessment (detection bias), whether all the randomised patients were accounted
      for in the analysis (attrition bias) and the presence of selective outcome
      reporting. MAIN RESULTS: We included four studies with 166 participants. No
      studies compared the effects of home-based upper limb therapy programmes with
      placebo or no intervention. Three studies compared the effects of home-based
      upper limb therapy programmes with usual care. PRIMARY OUTCOMES: we found no
      statistically significant result for performance of ADL (mean difference (MD)
      2.85; 95% confidence interval (CI) -1.43 to 7.14) or functional movement of the
      upper limb (MD 2.25; 95% CI -0.24 to 4.73)). SECONDARY OUTCOMES: no statistically
      significant results for extended ADL (MD 0.83; 95% CI -0.51 to 2.17)) or upper
      limb motor impairment (MD 1.46; 95% CI -0.58 to 3.51). One study compared the
      effects of a home-based upper limb programme with the same upper limb programme
      based in hospital, measuring upper limb motor impairment only; we found no
      statistically significant difference between groups (MD 0.60; 95% CI -8.94 to
      10.14). AUTHORS' CONCLUSIONS: There is insufficient good quality evidence to make
      recommendations about the relative effect of home-based therapy programmes
      compared with placebo, no intervention or usual care.

PMID- 22592716
TI  - Treatments for adults with prominent lower front teeth.
AB  - BACKGROUND: Prominent lower front teeth may be associated with a large or
      prognathic lower jaw (mandible) or a small or retrusive upper jaw (maxilla).
      Edward Angle, who may be considered the father of modern orthodontics, classified
      the malocclusion in this situation as Class III. The individual is described as
      having a negative or reverse overjet as the lower front teeth are more prominent
      than the upper front teeth. OBJECTIVES: The purpose of this systematic review was
      to evaluate different treatments of Angle Class III malocclusion in adults.
      SEARCH METHODS: The following databases were searched: Cochrane Oral Health Group
      Trials Register (to 22 March 2012); CENTRAL (The Cochrane Library 2012, Issue 1);
      MEDLINE via OVID (1950 to 22 March 2012); EMBASE via OVID (1980 to 22 March
      2012); LILACs (1982 to 22 March 2012); BBO (1986 to 22 March 2012); and SciELO
      (1997 to 22 March 2012). SELECTION CRITERIA: All randomized or quasi-randomized
      controlled trials of treatments for adults with an Angle Class III malocclusion
      were included. DATA COLLECTION AND ANALYSIS: Three review authors independently
      assessed the eligibility of the identified reports. Two review authors
      independently extracted data and assessed the risk of bias in the included
      studies. The mean differences with 95% confidence intervals were calculated for
      continuous data. MAIN RESULTS: Two randomized controlled trials were included in
      this review. There are different types of surgery for this type of malocclusion
      but only trials of mandible reduction surgery were identified. One trial compared
      intraoral vertical ramus osteotomy (IVRO) with sagittal split ramus osteotomy
      (SSRO) and the other trial compared vertical ramus osteotomy (VRO) with and
      without osteosynthesis. Neither trial found any difference between the two
      treatments. The trials did not provide adequate data for assessing effectiveness
      of the techniques described. AUTHORS' CONCLUSIONS: There is insufficient evidence
      from the two included trials, to conclude that one procedure is better or worse
      than another. The included trials compared different interventions and were at
      high risk of bias and therefore no implications for practice can be given.
      Further high quality randomized controlled trials with long term follow-up are
      required.

PMID- 22592717
TI  - Knee length versus thigh length graduated compression stockings for prevention of
      deep vein thrombosis in postoperative surgical patients.
AB  - BACKGROUND: Graduated compression stockings (GCS) are a valuable means of
      thromboprophylaxis in hospitalised postoperative surgical patients. But it is
      still unclear whether knee length graduated compression stockings (KL) or thigh
      length (TL) stockings are more effective. OBJECTIVES: The aim of this review was
      to systematically analyse the randomised, controlled trials that have evaluated
      the effectiveness of KL versus TL GCS as a thromboprophylaxis tool in
      hospitalised patients undergoing various types of surgery. SEARCH METHODS: The
      Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched
      the Specialised Register (last searched February 2012) and CENTRAL (2012, Issue
      1). The authors searched MEDLINE and EMBASE (until 27 February 2012) and they
      also searched the reference lists of relevant articles to identify additional
      trials. SELECTION CRITERIA: Randomised controlled trials published in any
      language on KL versus TL GCS used as a thromboprophylaxis tool in hospitalised
      patients of any age and either gender. DATA COLLECTION AND ANALYSIS: Data
      extraction was undertaken independently by two review authors using data
      extraction sheets and confirmed by the third review author. MAIN RESULTS: Three
      studies, with a combined total of 496 patients, matched the inclusion criteria
      for this review. All three included studies evaluated the role of KL and TL in
      thromboprophylaxis among a group of postoperative patients. These studies showed
      no significant difference in the ability of the two modalities of leg compression
      to reduce the incidence of deep vein thrombosis in postoperative patients. In
      both the fixed-effect model (odds ratio (OR) 1.55, 95% confidence interval (CI)
      0.78 to 3.07, P = 0.21) and random-effects model (OR 1.32, 95% CI 0.43 to 4.06, P
      = 0.63) KL graduated compression stockings were as effective as TL stockings in
      thromboprophylaxis. However, there was significant heterogeneity (Tau(2) = 0.50;
      Chi(2) = 4.12, df = 2 (P = 0.13); I(2) = 51%) among trials. Results of this
      review may be considered weak because there was significant heterogeneity among
      included trials resulting from inadequate randomisation techniques, allocation
      concealment, power calculations and the absence of intention-to-treat analysis.
      AUTHORS' CONCLUSIONS: This review found that there is insufficient high quality
      evidence to determine whether or not KL and TL GCS differ in their effectiveness
      in terms of reducing the incidence of deep vein thrombosis (DVT) in hospitalised
      patients.  A major multicentre RCT is required to address this issue. In the
      meantime, the decision on which type of stocking to use in clinical practice is
      likely to be influenced by factors such as patient compliance, ease of use and
      cost implications.

PMID- 22592718
TI  - WITHDRAWN: Effectiveness and safety of first-line tenofovir + emtricitabine +
      efavirenz for patients with HIV.
AB  - BACKGROUND: The current recommended antiretroviral treatment is a highly active
      antiretroviral therapy (HAART). Although HAART has been associated with improved
      clinical response to treatment, issues of adherence and viral resistance are
      major challenges limiting its success. There is a need for an effective and safe
      first-line regimen, to cope with the ever-increasing incidence of non-adherence
      and primary resistance. A more recent first-line treatment regimen consists of
      Tenofovir (TDF, 300 mg) + Emtricitabine (FTC, 200 mg) + Efavirenz (EFV, 600 mg).
      OBJECTIVES: To evaluate the effects and safety of TDF + FTC + EFV as first-line
      treatment for patients with HIV. SEARCH METHODS: We searched the Cochrane Central
      Register of Controlled Trials, EMBASE, GATEWAY, LILACS, PubMed, AEGIS, and the
      WHO prospective clinical trials registry in November 2011. SELECTION CRITERIA:
      Randomized controlled trials evaluating the effects of TDF + FTC + EFV compared
      with other HAART regimens. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed trial eligibility and risk of bias, and extracted data
      from the included study. MAIN RESULTS: Only one study involving 517
      antiretroviral-naive HIV infected adults was included in this review.
      Participants were randomly assigned to receive either a regimen of TDF (300 mg),
      FTC (200mg), and EFV (600mg ) once daily; or a regimen of fixed-dose zidovudine
      (AZT) (300 mg) and lamivudine (3TC) (150 mg) twice daily plus EFV (600mg) once
      daily. Significantly more patients in the TDF-FTC group reached and maintained
      HIV RNA levels of less than 50 copies per milliliter compared to the AZT- 3TC
      group (RR 1.13; 95% CI 1.02 to 1.25). Also, more participants in the TDF-FTC
      group had greater increase from baseline CD4 cell counts compared to the AZT-3TC
      group (190 vs. 158 cells per mm(3)). More patients in the AZT-3TC group than in
      the TDF-FTC group had adverse events resulting in discontinuation of the study
      drugs (9% vs. 4%, respectively; P = 0.02). There was no statistically significant
      difference in all cause mortality (RR 0.50; 95% CI 0.05 to 5.46). AUTHORS'
      CONCLUSIONS: Only one trial has shown beneficial effects and safety of TDF+ FTC +
      EFV as first-line treatment for patients with HIV. The effects and safety of TDF
      + FTC + EFV as first-line treatment for patients with HIV cannot be assessed on
      the basis of only one trial. Further studies evaluating the effects and safety of
      TDF + FTC + EFV as first-line treatment for patients with HIV are needed.

PMID- 22592719
TI  - Carnitine for fatigue in multiple sclerosis.
AB  - BACKGROUND: Fatigue is reported to occur in up to 92% of patients with multiple
      sclerosis (MS) and has been described as the most debilitating of all MS symptoms
      by 28% to 40% of MS patients. OBJECTIVES: To assess whether carnitine (enteral or
      intravenous) supplementation can improve the quality of life and reduce the
      symptoms of fatigue in patients with MS-related fatigue and to identify any
      adverse effects of carnitine when used for this purpose. SEARCH METHODS: A
      literature search was performed using Cochrane MS Group Trials Register (09
      September 2011), Cochrane Central Register of Controlled Trials (CENTRAL) "The
      Cochrane Library 2011, issue 3", MEDLINE (PubMed) (1966-09 September 2011),
      EMBASE (1974-09 September 2011), and www.clinicaltrials.gov for ongoing trials
      retrieval. Reference lists of review articles and primary studies were also
      screened. A hand search of the abstract book of recent relevant conference
      symposia was also conducted. Personal contact with MS experts and a manufacturer
      (Source Naturals, United States) of carnitine formulation was contacted to
      determine if they knew of other clinical trials. No language restrictions were
      applied. SELECTION CRITERIA: Full reports of published and unpublished randomized
      controlled trials and quasi-randomized trials of any carnitine intervention in
      adults affected by multiple sclerosis with a clinical diagnosis of fatigue
      associated with multiple sclerosis were included. DATA COLLECTION AND ANALYSIS:
      Data from the eligible trials was extracted and coded using a standardized data
      extraction form and entered into RevMan 5. Discrepancies were to be resolved by
      discussion with a third reviewer, however this was not necessary.The quality
      items to be assessed were method of randomization, allocation concealment,
      blinding (participants, investigators, outcome assessors and data analysis),
      intention-to-treat analysis and completeness of follow up. MAIN RESULTS: The
      search identified one ongoing randomized, placebo-controlled, cross-over trial
      (expected completion 2013) and one completed randomized, active-comparator, cross
      over trial. In the completed study, adult patients with relapsing-remitting and
      secondary progressive MS were exposed to both acetyl L-carnitine 2 grams daily
      and amantadine 200 mg daily The effects of carnitine on fatigue are unclear.
      There was no difference between carnitine and amantadine for the number of
      patients withdrawing from the study due to an adverse event (relative risk ratio
      0.20; 95% confidence interval 0.03 to 1.55) and no patients experienced a serious
      adverse event in either treatment group. Mortality and quality of life were not
      reported. AUTHORS' CONCLUSIONS: There is insufficient evidence that carnitine for
      the treatment of MS-related fatigue offers a therapeutic advantage over placebo
      or active comparators. Results of the ongoing trial are eagerly anticipated in
      order to provide clarity.

PMID- 22592720
TI  - Cardiopulmonary interventions to decrease blood loss and blood transfusion
      requirements for liver resection.
AB  - BACKGROUND: Blood loss during liver resection is considered one of the most
      important factors affecting the peri-operative outcomes of patients undergoing
      liver resection. OBJECTIVES: To determine the benefits and harms of
      cardiopulmonary interventions to decrease blood loss and to decrease allogeneic
      blood transfusion requirements in patients undergoing liver resections. SEARCH
      METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials
      Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The
      Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until
      January 2012 to identify randomised trials. SELECTION CRITERIA: We included all
      randomised clinical trials comparing various cardiopulmonary interventions aimed
      at decreasing blood loss and allogeneic blood transfusion requirements in
      patients undergoing liver resection. Trials were included irrespective of whether
      they included major or minor liver resections of normal or cirrhotic livers,
      vascular occlusion was used or not, and irrespective of the reason for liver
      resection. DATA COLLECTION AND ANALYSIS: Two authors independently identified
      trials for inclusion and independently extracted data. We analysed the data with
      both the fixed-effect and the random-effects models using RevMan Analysis. For
      each outcome we calculated the risk ratio (RR), mean difference (MD), or
      standardised mean difference (SMD) with 95% confidence intervals (CI) based on
      intention-to-treat analysis or available case analysis. For dichotomous outcomes
      with only one trial included under the outcome, we performed the Fisher's exact
      test. MAIN RESULTS: Ten trials involving 617 patients satisfied the inclusion
      criteria. The interventions included low central venous pressure (CVP),
      autologous blood donation, haemodilution, haemodilution with controlled
      hypotension, and hypoventilation. Only one or two trials were included under most
      comparisons. All trials had a high risk of bias. There was no significant
      difference in the peri-operative mortality in any of the comparisons: low CVP
      versus no intervention (3 trials, 0/88 (0%) patients in the low CVP group versus
      1/89 (1.1%) patients in the no intervention group); autologous blood donation
      versus no intervention (1 trial, 0/40 (0%) versus 0/39 (0%)); haemodilution
      versus no intervention (2 trials, 1/73 (1.4%) versus 3/77 (3.9%) in one of these
      trials); haemodilution with controlled hypotension versus no intervention (1
      trial, 0/10 (0%) versus 0/10 (0%)); haemodilution with bovine haemoglobin (HBOC
      201) versus haemodilution with hydroxy ethyl starch (HES) (1 trial, 1/6 (16.7%)
      versus 0/6 (0%)); hypoventilation versus no intervention (1 trial, 0/40 (0%)
      versus 0/39 (0%)). None of the trials reported long-term survival or quality of
      life. The risk ratio of requiring allogeneic blood transfusion was significantly
      lower in the haemodilution versus no intervention groups (3 trials, 16/115
      (weighted proportion = 14.2%) versus 41/118 (34.7%), RR 0.41 (95% CI 0.25 to
      0.66), P = 0.0003); and for haemodilution with controlled hypotension versus no
      intervention (1 trial, 0/10 (0%) versus 10/10 (100%), P < 0.0001). There were no
      significant differences in the allogeneic transfusion requirements in the other
      comparisons which reported this outcome, such as low CVP versus no intervention,
      autologous blood donation versus control, and hypoventilation versus no
      intervention. AUTHORS' CONCLUSIONS: None of the interventions seemed to decrease
      peri-operative morbidity or offer any long-term survival benefit. Haemodilution
      shows promise in the reduction of blood transfusion requirements in liver
      resection surgery. However, there is a high risk of type I (erroneously
      concluding that an intervention is beneficial when it is actually not beneficial)
      and type II errors (erroneously concluding that an intervention is not beneficial
      when it is actually beneficial) because of the few trials included, the small
      sample size in each trial, and the high risk of bias in the trials. Further
      randomised clinical trials with low risk of bias and random errors that assess
      clinically important outcomes such as peri-operative mortality are necessary to
      assess any cardiopulmonary interventions aimed at decreasing blood loss and blood
      transfusion requirements in patients undergoing liver resections. Trials need to
      be designed to assess the effect of a combination of different interventions in
      liver resections.

PMID- 22592721
TI  - Spiritual and religious interventions for well-being of adults in the terminal
      phase of disease.
AB  - BACKGROUND: As terminal disease progresses, health deteriorates and the end of
      life approaches, people may ask "Why this illness? Why me? Why now?" Such
      questions may invoke, rekindle or intensify spiritual or religious concerns.
      Although the processes by which these associations occur are poorly understood,
      there is some research evidence for associations that are mainly positive between
      spiritual and religious awareness and wellness, such as emotional health.
      OBJECTIVES: This review aimed to describe spiritual and religious interventions
      for adults in the terminal phase of a disease and to evaluate their effectiveness
      on well-being. SEARCH METHODS: We searched 14 databases to November 2011,
      including the Cochrane Central Register of Controlled Trials and MEDLINE.
      SELECTION CRITERIA: We included randomised controlled trials (RCTS) if they
      involved adults in the terminal phase of a disease and if they evaluated outcomes
      for an intervention that had a spiritual or religious component. Primary outcomes
      were well-being, coping with the disease and quality of life. DATA COLLECTION AND
      ANALYSIS: In accordance with the inclusion criteria, two review authors
      independently screened citations. One review author extracted data which was then
      checked by another review author. We considered meta-analysis for studies with
      comparable characteristics. MAIN RESULTS: Five RCTs (1130 participants) were
      included. Two studies evaluated meditation, the others evaluated multi
      disciplinary palliative care interventions that involved a chaplain or spiritual
      counsellor as a member of the intervention team. The studies evaluating
      meditation found no overall significant difference between those receiving
      meditation or usual care on quality of life or well-being. However, when
      meditation was combined with massage in the medium term it buffered against a
      reduction in quality of life. In the palliative care intervention studies there
      was no significant difference in quality of life or well-being between the trial
      arms. Coping with the disease was not evaluated in the studies. The quality of
      the studies was limited by under-reporting of design features. AUTHORS'
      CONCLUSIONS: We found inconclusive evidence that interventions with spiritual or
      religious components for adults in the terminal phase of a disease may or may not
      enhance well-being. Such interventions are under-evaluated. All five studies
      identified were undertaken in the same country, and in the multi-disciplinary
      palliative care interventions it is unclear if all participants received support
      from a chaplain or a spiritual counsellor. Moreover, it is unclear in all the
      studies whether the participants in the comparative groups received spiritual or
      religious support, or both, as part of routine care or from elsewhere. The
      paucity of quality research indicates a need for more rigorous studies.

PMID- 22592722
TI  - Radiotherapy and chemoradiation after surgery for early cervical cancer.
AB  - BACKGROUND: This is an updated version of the original Cochrane review first
      published in Issue 4, 2009. There is an ongoing debate about the indications for,
      and value of, adjuvant pelvic radiotherapy after radical surgery in women with
      early cervical cancer. Certain combinations of pathological risk factors are
      thought to represent sufficient risk for recurrence, that they justify the use of
      postoperative pelvic radiotherapy, though this has never been shown to improve
      overall survival, and use of more than one type of treatment (surgery and
      radiotherapy) increases the risks of side effects and complications. OBJECTIVES:
      To evaluate the effectiveness and safety of adjuvant therapies (radiotherapy,
      chemotherapy followed by radiotherapy, chemoradiation) after radical hysterectomy
      for early-stage cervical cancer (FIGO stages IB1, IB2 or IIA). SEARCH METHODS:
      For the original review, we searched the Cochrane Central Register of Controlled
      Trials (CENTRAL), Issue 4, 2008. The Cochrane Gynaecological Cancer Group Trials
      Register, MEDLINE (January 1950 to November 2008), EMBASE (1950 to November
      2008). We also searched registers of clinical trials, abstracts of scientific
      meetings, reference lists of included studies and contacted experts in the field.
      For this update, we extended the database searches to September 2011 and searched
      the MetaRegister for ongoing trials. SELECTION CRITERIA: Randomised controlled
      trials (RCTs) that compared adjuvant therapies (radiotherapy, chemotherapy
      followed by radiotherapy, or chemoradiation) with no radiotherapy or
      chemoradiation, in women with a confirmed histological diagnosis of early
      cervical cancer who had undergone radical hysterectomy and dissection of the
      pelvic lymph nodes. DATA COLLECTION AND ANALYSIS: Two review authors
      independently abstracted data and assessed risk of bias. Information on grade 3
      and 4 adverse events was collected from the trials. Results were pooled using
      random-effects meta-analyses. MAIN RESULTS: Two RCTs, which compared adjuvant
      radiotherapy with no adjuvant radiotherapy, met the inclusion criteria; they
      randomised and assessed 397 women with stage IB cervical cancer. Meta-analysis of
      these two RCTs indicated no significant difference in survival at 5 years between
      women who received radiation and those who received no further treatment (risk
      ratio (RR) = 0.8; 95% confidence interval (CI) 0.3 to 2.4). However, women who
      received radiation had a significantly lower risk of disease progression at 5
      years (RR 0.6; 95% CI 0.4 to 0.9).Although the risk of serious adverse events was
      consistently higher if women received radiotherapy rather than no further
      treatment, these increased risks were not statistically significant, probably
      because the rate of adverse events was low. AUTHORS' CONCLUSIONS: We found
      evidence, of moderate quality, that radiation decreases the risk of disease
      progression compared with no further treatment, but little evidence that it might
      improve overall survival, in stage IB cervical cancer. The evidence on serious
      adverse events was equivocal.

PMID- 22592723
TI  - Interventions for female pattern hair loss.
AB  - BACKGROUND: Female pattern hair loss, or androgenic alopecia, is the most common
      type of hair loss affecting women. It is characterised by progressive shortening
      of the duration of the growth phase of the hair with successive hair cycles, and
      progressive follicular miniaturisation with conversion of terminal to vellus hair
      follicles (terminal hairs are thicker and longer, while vellus hairs are soft,
      fine, and short). The frontal hair line may or may not be preserved. Hair loss
      can have a serious psychological impact on people. OBJECTIVES: To determine the
      effectiveness and safety of the available options for the treatment of female
      pattern hair loss in women. SEARCH METHODS: We searched the following databases
      up to October 2011: the Cochrane Skin Group Specialised Register, CENTRAL in The
      Cochrane Library (2011, Issue 4), MEDLINE (from 1946), EMBASE (from 1974),
      PsycINFO (from 1806), AMED (from 1985), LILACS (from 1982), PubMed (from 1947),
      Web of Science (from 1945), and reference lists of articles. We also searched
      several online trials registries for ongoing trials. SELECTION CRITERIA:
      Randomised controlled trials that assessed the effectiveness of interventions for
      female pattern hair loss in women. DATA COLLECTION AND ANALYSIS: Two review
      authors independently assessed trial quality and extracted data. MAIN RESULTS:
      Twenty two trials, comprising 2349 participants, were included. A wide range of
      interventions were evaluated, with 10 studies investigating the different
      concentrations of minoxidil. Pooled data from 4 studies indicated that a greater
      proportion of participants (121/488) treated with minoxidil reported a moderate
      increase in their hair regrowth when compared with placebo (64/476) (risk ratio
      (RR) = 1.86, 95% confidence interval (CI) 1.42 to 2.43). In 7 studies, there was
      an important increase of 13.28 in total hair count per cm(2) in the minoxidil
      group compared to the placebo group (95% CI 10.89 to 15.68). There was no
      difference in the number of adverse events in the twice daily minoxidil and
      placebo intervention groups, with the exception of a reported increase of adverse
      events (additional hair growth on areas other than the scalp) with minoxidil (5%)
      twice daily. Most of the other comparisons consisted of single studies. These
      were assessed as high risk of bias: They did not address our prespecified
      outcomes and provided limited evidence of either the efficacy or safety of these
      interventions. AUTHORS' CONCLUSIONS: Although more than half of the included
      studies were assessed as being at high risk of bias, and the rest at unclear,
      there was evidence to support the effectiveness and safety of topical minoxidil
      in the treatment of female pattern hair loss. Further direct comparison studies
      of minoxidil 5% applied once a day, which could improve adherence when compared
      to minoxidil 2% twice daily, are still required. Consideration should also be
      given to conducting additional well-designed, adequately-powered randomised
      controlled trials investigating several of the other treatment options.

PMID- 22592724
TI  - Iron for restless legs syndrome.
AB  - BACKGROUND: Restless legs syndrome (RLS) is a common neurologic syndrome and is
      associated with iron deficiency in many patients. It is unclear whether iron
      therapy is effective treatment for RLS. OBJECTIVES: The objective of this review
      was to assess the effects of iron supplementation (oral or intravenous) for
      patients with RLS. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL), MEDLINE (Jan 1995 to April 2011); EMBASE (Jan 1995
      to April 2011); PsycINFO (Jan 1995 to April 2011); and CINAHL (Jan 1995 to April
      2011). Corresponding authors of included trials and additional members of the
      International Restless Legs Syndrome Study Group were contacted to locate
      additional published or unpublished trials. SELECTION CRITERIA: Controlled trials
      comparing any formulation of iron with placebo, other medications, or no
      treatment in adults diagnosed with RLS according to expert clinical interview or
      explicit diagnostic criteria. DATA COLLECTION AND ANALYSIS: Two review authors
      extracted data and at least two authors assessed trial quality. We contacted
      trial authors for missing data. MAIN RESULTS: Six studies (192 total subjects)
      were identified and included in this analysis. The quality of trials was
      variable. Our primary outcome was restlessness or uncomfortable leg sensations,
      which was quantified using the IRLS severity scale in four trials and another RLS
      symptom scale in a fifth trial. Combining data from the four trials using the
      IRLS severity scale, there was no clear benefit from iron therapy (mean
      difference in IRLS severity scores of -3.79, 95% CI: -7.68 to 0.10, p = 0.06).
      However, the fifth trial did find iron therapy to be beneficial (median decrease
      of 3 points in the iron group and no change in the placebo group on a 10 point
      scale of RLS symptoms, p = 0.01). Quality of life was improved in the iron group
      relative to placebo in some studies but not others. Changes in periodic limb
      movements were not different between groups (measured in two studies). Objective
      sleep quality, subjective sleep quality and daytime functioning were not
      different between treatment groups in the studies that assessed them. The single
      study of subjects with end stage renal disease did show a benefit of therapy.
      Most trials did not require subjects to have co-morbid iron deficiency and
      several excluded patients with severe anemia. The single study that was limited
      to iron deficient subjects did not show clear benefit of iron supplementation on
      RLS symptoms. There was no clear superiority of oral or intravenous delivery of
      iron. Iron therapy did not result in significantly more side effects than placebo
      (RR 1.39, 95% CI 0.85 to 2.27). AUTHORS' CONCLUSIONS: There is insufficient
      evidence to determine whether iron therapy is beneficial for the treatment of
      RLS. Further research to determine whether some or all types of RLS patients may
      benefit from iron therapy, as well as the best route of iron administration, is
      needed.

PMID- 22592725
TI  - Maintenance treatment with antipsychotic drugs for schizophrenia.
AB  - BACKGROUND: The symptoms and signs of schizophrenia have been firmly linked to
      high levels of dopamine in specific areas of the brain (limbic system).
      Antipsychotic drugs block the transmission of dopamine in the brain and reduce
      the acute symptoms of the disorder. This review examined whether antipsychotic
      drugs are also effective for relapse prevention. OBJECTIVES: To review the
      effects of maintaining antipsychotic drugs for people with schizophrenia compared
      to withdrawing these agents. SEARCH METHODS: We searched the Cochrane
      Schizophrenia Group's Specialised Register (November 2008), with additional
      searches of MEDLINE, EMBASE and clinicaltrials.gov (June 2011). SELECTION
      CRITERIA: We included all randomised trials comparing maintenance treatment with
      antipsychotic drugs and placebo for people with schizophrenia or schizophrenia
      like psychoses. DATA COLLECTION AND ANALYSIS: We extracted data independently.
      For dichotomous data we calculated relative risks (RR) and their 95% confidence
      intervals (CI) on an intention-to-treat basis based on a random-effects model.
      For continuous data, we calculated mean differences (MD) or standardised mean
      differences (SMD) again based on a random-effects model. MAIN RESULTS: The review
      currently includes 65 randomised controlled trials (RCT(s)) and 6493 participants
      comparing antipsychotic medication with placebo. The trials were published from
      1959 to 2011 and their size ranged between 14 and 420 participants. In many
      studies the methods of randomisation, allocation and blinding were poorly
      reported. Although this and other potential sources of bias limited the overall
      quality, the efficacy of antipsychotic drugs for maintenance treatment in
      schizophrenia was clear. Antipsychotic drugs were significantly more effective
      than placebo in preventing relapse at seven to 12 months (primary outcome; drug
      27%, placebo 64%, 24 RCT(s), n=2669, RR 0.40 CI 0.33 to 0.49, number needed to
      treat for an additional beneficial outcome (NNTB 3 CI 2 to 3). Hospitalisation
      was also reduced, however, the baseline risk was lower (drug 10%, placebo 26%, 16
      RCT(s), n=2090, RR 0.38 CI 0.27 to 0.55, NNT 5 CI 4 to 9). More participants in
      the placebo group than in the antipsychotic drug group left the studies early due
      to any reason (at 7-12 months: drug 38%, placebo 66%, 18 RCT(s), n=2420, RR 0.55
      CI 0.46 to 0.66, NNTB 4 CI 3 to 5) and due to inefficacy of treatment (at 7-12
      months: drug 20%, placebo 50%, 18 RCT(s), n=2420, RR 0.36 CI 0.28 to 0.45, NNTB 3
      CI 2 to 4). Quality of life was better in drug-treated participants (3 RCT(s),
      n=527, SMD -0.62 CI -1.15 to -0.09). Conversely, antipsychotic drugs as a group
      and irrespective of duration, were associated with more participants experiencing
      movement disorders (e.g. at least one movement disorder: drug 16%, placebo 9%, 22
      RCT(s), n=3411, RR 1.55 CI 1.25 to 1.93, NNTH 25 CI 13 to 100), sedation (drug
      13%, placebo 9%, 10 RCT(s), n=146, RR 1.50 CI 1.22 to 1.84, number needed to
      treat for an additional harmful outcome (NNTH) not significant) and weight gain
      (drug 10%, placebo 6%, 10 RCT(s), n=321, RR 2.07 CI 1.31 to 3.25, NNTH 20 CI 14
      to 33). The results of the primary outcome were robust in a number of subgroup,
      meta-regression and sensitivity analyses, the main exception being that the drug
      placebo difference in longer trials was smaller than in shorter trials. AUTHORS'
      CONCLUSIONS: The results clearly demonstrate the superiority of antipsychotic
      drugs compared to placebo in preventing relapse. This effect must be weighed
      against the side effects of antipsychotic drugs. Future studies should focus on
      outcomes of social participation and clarify the long-term morbidity and
      mortality associated with these drugs.

PMID- 22592726
TI  - WITHDRAWN: Coenzyme Q10 for Parkinson's disease.
AB  - BACKGROUND: A number of preclinical studies in both in vitro and in vivo models
      of Parkinson's disease have demonstrated that coenzyme Q10 can protect the
      nigrostriatal dopaminergic system. Some clinical trials have looked at the
      neuroprotective effects of coenzyme Q10 in patients with early and midstage
      Parkinson's disease. OBJECTIVES: To assess the evidence from randomized
      controlled trials on the efficacy and safety of treatment with coenzyme Q10
      compared to placebo in patients with early and midstage Parkinson's disease.
      SEARCH METHODS: We searched the Cochrane Movment Disorders Group Trials Register,
      CENTRAL (The Cochrane Library 2009, Issue 4), MEDLINE (January 1966 to March
      2011), and EMBASE (January 1985 to March 2011). We handsearched the references
      quoted in the identified trials, congress reports from the most important
      neurological association and movement disorder societies in Europe and America
      (March 2011), checked reference lists of relevant studies and contacted other
      researchers. SELECTION CRITERIA: We included randomized controlled trials (RCTs)
      that compared coenzyme Q10 to placebo for patients who suffered early and
      midstage primary Parkinson's disease. Studies in which the method of
      randomization or concealment were unknown were included. Cross-over studies were
      excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed
      trial quality and extracted data. All disagreements were resolved by consensus
      between authors and were explained. We attempted to contact the authors of
      studies for further details if any data were missing and to establish the
      characteristics of unpublished trials through correspondence with the trial
      coordinator or principal investigator. Adverse effects information was collected
      from the trials. MAIN RESULTS: Four randomized, double-blind, placebo-controlled
      trials with a total of 452 patients met the inclusion criteria and were included
      in the review. In overall, there were improvements in activities of daily living
      (ADL) UPDRS (WMD -3.12, 95% CI -5.88 to -0.36) and Schwab and England (WMD 4.43,
      95% CI 0.05 to 8.81) for coenzyme Q10 at 1200 mg/d for 16 months versus
      placebo.In safety outcomes, only the risk ratios (RR) of pharyngitis (RR 1.04,
      95% CI 0.18 to 5.89) and diarrhea (RR 1.39, 95% CI 0.62 to 3.16) are mild
      elevated between coenzyme Q10 therapy and placebo and there were no differences
      in the number of withdrawals due to adverse effects (RR 0.61, 95% CI 0.23 to
      1.62). AUTHORS' CONCLUSIONS: Coenzyme Q10 therapy with 1200 mg/d for 16 months
      was well tolerated by patients with Parkinson's disease. The improvements in ADL
      UPDRS and Schwab and England were positive, but it need to be further confirmed
      by larger sample. For total and other subscores of UPDRS, the effects of coenzyme
      Q10 seemed to be less clear.

PMID- 22592727
TI  - Interventions to improve the appropriate use of polypharmacy for older people.
AB  - BACKGROUND: Inappropriate polypharmacy is a particular concern in older people
      and is associated with negative health outcomes. Choosing the best interventions
      to improve appropriate polypharmacy is a priority, hence there is growing
      interest in appropriate polypharmacy, where many medicines may be used to achieve
      better clinical outcomes for patients. OBJECTIVES: This review sought to
      determine which interventions alone, or in combination, are effective in
      improving the appropriate use of polypharmacy and reducing medication-related
      problems in older people. SEARCH METHODS: A range of literature databases
      including MEDLINE and EMBASE were searched in addition to handsearching reference
      lists. Search terms included polypharmacy, Beers criteria, medication
      appropriateness and inappropriate prescribing. SELECTION CRITERIA: A range of
      study designs were eligible. Eligible studies described interventions affecting
      prescribing aimed at improving appropriate polypharmacy in people aged 65 years
      and older where a validated measure of appropriateness was used (e.g. Beers
      criteria or Medication Appropriateness Index - MAI). DATA COLLECTION AND
      ANALYSIS: Three authors independently reviewed abstracts of eligible studies,
      extracted data and assessed risk of bias of included studies. Study specific
      estimates were pooled, using a random-effects model to yield summary estimates of
      effect and 95% confidence intervals. MAIN RESULTS: Electronic searches identified
      2200 potentially relevant citations, of which 139 were examined in detail.
      Following assessment, 10 studies were included. One intervention was computerised
      decision support and nine were complex, multifaceted pharmaceutical care provided
      in a variety of settings. Appropriateness of prescribing was measured using the
      MAI score postintervention (seven studies) and/or Beers criteria (four studies).
      The interventions included in this review demonstrated a reduction in
      inappropriate medication use. A mean difference of -6.78 (95% CI -12.34 to -1.22)
      in the change in MAI score in favour of the intervention group (four studies).
      Postintervention pooled data (five studies) showed a mean reduction of -3.88 (95%
      CI -5.40 to -2.35) in the summated MAI score and a mean reduction of -0.06 (95%
      CI -0.16 to 0.04) in the number of Beers drugs per patient (three studies).
      Evidence of the effect of the interventions on hospital admissions (four studies)
      was conflicting. Medication-related problems, reported as the number of adverse
      drug events (three studies), reduced significantly (35%) postintervention.
      AUTHORS' CONCLUSIONS: It is unclear if interventions to improve appropriate
      polypharmacy, such as pharmaceutical care, resulted in a clinically significant
      improvement; however, they appear beneficial in terms of reducing inappropriate
      prescribing and medication-related problems.

PMID- 22592728
TI  - Stent placement versus surgery for coarctation of the thoracic aorta.
AB  - BACKGROUND: Coarctation of the aorta (CoA) accounts for 5% to 7% of congenital
      heart disease, with an incidence of 0.3 to 0.4 per 1000 live births. Surgery was
      the only choice of therapy for CoA until 1982 when balloon angioplasty became an
      available alternative for its treatment. Re-coarctation, aneurysm and aortic
      dissection remain the disadvantages of both treatments. To avoid those
      disadvantages, in 1990 endovascular stents were introduced for native coarctation
      and re-coarctation and since then they have become an alternative approach to
      surgical repair. The best approach to treat the CoA, whether open surgery or by
      stent placement, is not clear. OBJECTIVES: To analyze the effectiveness and
      safety of stent placement compared with open surgery in patients with coarctation
      of the thoracic aorta. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases
      Group searched their Specialised Register (last searched September 2011) and
      CENTRAL (2011, Issue 3). We also searched MEDLINE, EMBASE, CINAHL, AMED, Web of
      Science and LILACS (last searched in September 2011). We evaluated the located
      references and applied the inclusion criteria to selected studies. There was no
      restriction on language. SELECTION CRITERIA: Randomized or quasi-randomized
      controlled clinical trials that compared patients with CoA undergoing open
      surgery or stent placement. DATA COLLECTION AND ANALYSIS: The review authors
      independently assessed the studies identified for eligibility for inclusion. We
      excluded studies after a consensus meeting. MAIN RESULTS: All identified studies
      were screened and had the selection criteria applied to the title and abstract.
      In total, we selected five studies for full-text analysis. After detailed
      evaluation, we excluded all studies because there was no comparison between stent
      placement and open surgery. AUTHORS' CONCLUSIONS: There is insufficient evidence
      with regards to the best treatment for coarctation of the thoracic aorta. This
      review suggests a need to perform a randomized controlled clinical trial with
      emphasis on the allocation method, evaluation of primary outcomes, size and
      quality of the sample, and long-term follow-up.

PMID- 22592729
TI  - Nutritional support for liver disease.
AB  - BACKGROUND: Weight loss and muscle wasting are commonly found in patients with
      end-stage liver disease. Since there is an association between malnutrition and
      poor clinical outcome, such patients (or those at risk of becoming malnourished)
      are often given parenteral nutrition, enteral nutrition, or oral nutritional
      supplements. These interventions have costs and adverse effects, so it is
      important to prove that their use results in improved morbidity or mortality, or
      both. OBJECTIVES: To assess the beneficial and harmful effects of parenteral
      nutrition, enteral nutrition, and oral nutritional supplements on the mortality
      and morbidity of patients with underlying liver disease. SEARCH METHODS: The
      following computerised databases were searched: the Cochrane Hepato-Biliary Group
      Controlled Trials Register, the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, and Science Citation Index
      Expanded (January 2012). In addition, reference lists of identified trials and
      review articles and Clinicaltrials.gov were searched. Trials identified in a
      previous systematic handsearch of Index Medicus were also considered.
      Handsearches of a number of medical journals, including abstracts from annual
      meetings, were done. Experts in the field and manufacturers of nutrient
      formulations were contacted for potential references. SELECTION CRITERIA:
      Randomised clinical trials (parallel or cross-over design) comparing groups of
      patients with any underlying liver disease who received, or did not receive,
      enteral or parenteral nutrition or oral nutritional supplements were identified
      without restriction on date, language, or publication status. Six categories of
      trials were separately considered: medical or surgical patients receiving
      parenteral nutrition, enteral nutrition, or supplements. DATA COLLECTION AND
      ANALYSIS: The following data were sought in each report: date of publication;
      geographical location; inclusion and exclusion criteria; the type of nutritional
      support and constitution of the nutrient formulation; duration of treatment; any
      nutrition provided to the controls; other interventions provided to the patients;
      number, sex, age of the study participants; hospital or outpatient status;
      underlying liver disease; risks of bias (sequence generation, allocation
      concealment, blinding, incomplete outcome reporting, intention-to-treat analysis,
      selective outcome reporting, others (vested interests, baseline imbalance, early
      stopping)); mortality; hepatic morbidity (development or resolution of ascites or
      hepatic encephalopathy, occurrence of gastrointestinal bleeding); quality of life
      scores; adverse events; infections; lengths of stay in the hospital or intensive
      care unit; costs; serum bilirubin; postoperative complications (surgical trials
      only); and nutritional outcomes (nitrogen balance, anthropometric measurements,
      body weight). The primary outcomes of this review were mortality, hepatic
      morbidity, quality of life, and adverse events. Data were extracted in duplicate;
      differences were resolved by consensus.Data for each outcome were combined in a
      meta-analysis (RevMan 5.1). Estimates were reported using risk ratios or mean
      differences, along with the 95% confidence intervals (CI). Both fixed-effect and
      random-effects models were employed; fixed-effect models were reported unless one
      model, but not the other, found a significant difference (in which case both were
      reported). Heterogeneity was assessed by the Chi(2) test and I(2) statistic.
      Subgroup analyses were planned to assess specific liver diseases (alcoholic
      hepatitis, cirrhosis, hepatocellular carcinoma), acute or chronic liver diseases,
      and trials employing standard or branched-chain amino acid formulations (for the
      hepatic encephalopathy outcomes). Sensitivity analyses were planned to compare
      trials at low and high risk of bias and trials reported as full papers. The
      following exploratory analyses were undertaken: 1) medical and surgical trials
      were combined for each nutritional intervention; 2) intention-to-treat analyses
      in which missing dichotomous data were imputed as best- and worst-case scenarios;
      3) all trials were combined to assess mortality; 4) effects were estimated by
      absolute risk reductions. MAIN RESULTS: Thirty-seven trials were identified; only
      one was at low risk of bias. Most of the analyses failed to find any significant
      differences. The significant findings that were found were the following: 1)
      icteric medical patients receiving parenteral nutrition had a reduced serum
      bilirubin (mean difference (MD) -2.86 mg%, 95% CI -3.82 mg% to -1.89 mg%, 3
      trials) and better nitrogen balance (MD 3.60 g/day, 95% CI 0.86 g/day to 6.34
      g/day, 1 trial); 2) surgical patients receiving parenteral nutrition had a
      reduced incidence of postoperative ascites only in the fixed-effect model (RR
      0.65, 95% CI 0.48 to 0.87, 2 trials, I(2) = 70%) and one trial demonstrated a
      reduction in postoperative complications, especially infections (pneumonia in
      particular); 3) enteral nutrition may have improved nitrogen balance in medical
      patients (although a combination of the three trials was not possible); 4) one
      surgical trial of enteral nutrition found a reduction in postoperative
      complications; and 5) oral nutritional supplements had several effects in medical
      patients (reduced occurrence of ascites (RR 0.57, 95% CI 0.37 to 0.88, 3 trials),
      possibly (significant differences only seen in the fixed-effect model) reduced
      rates of infection (RR 0.49, 95% CI 0.24 to 0.99, 3 trials, I(2) = 14%), and
      improved resolution of hepatic encephalopathy (RR 3.75, 95% CI 1.15 to 12.18, 2
      trials, I(2) = 79%). While there was no overall effect of the supplements on
      mortality in medical patients, the one low risk of bias trial found an increased
      risk of death in the recipients of the supplements. Three trials of supplements
      in surgical patients failed to show any significant differences. No new
      information was derived from the various subgroup or sensitivity analyses. The
      exploratory analyses were also unrevealing except for a logical conundrum. There
      was no difference in mortality when all of the trials were combined, but the
      trials of parenteral nutrition found that those recipients had better survival
      (RR 0.53, 95% CI 0.29 to 0.98, 10 trials). Either the former observation
      represents a type II error or the latter one a type I error. AUTHORS'
      CONCLUSIONS: The data do not compellingly justify the routine use of parenteral
      nutrition, enteral nutrition, or oral nutritional supplements in patients with
      liver disease. The fact that all but one of these trials were at high risks of
      bias even casts doubt on the few benefits that were demonstrated. Data from well
      designed and executed randomised trials that include an untreated control group
      are needed before any such recommendation can be made. Future trials have to be
      powered adequately to see small, but clinically important, differences.

PMID- 22592730
TI  - Chinese herbal medicines for threatened miscarriage.
AB  - BACKGROUND: Threatened miscarriage occurs in 10% to 15% of all pregnancies.
      Vaginal spotting or bleeding during early gestation is common, with nearly half
      of those pregnancies resulting in pregnancy loss. To date, there is no effective
      preventive treatment for threatened miscarriage. Chinese herbal medicines have
      been widely used in Asian countries for centuries and have become a popular
      alternative to Western medicines in recent years. Many studies claim to show that
      they can prevent miscarriage. However, there has been no systematic evaluation of
      the effectiveness of Chinese herbal medicines for threatened miscarriage.
      OBJECTIVES: To review the therapeutic effects of Chinese herbal medicines for the
      treatment of threatened miscarriage. SEARCH METHODS: We searched the Cochrane
      Pregnancy and Childbirth Group's Trials Register (31 January 2012), Chinese
      Biomedical Database (1978 to 31 January 2012), China Journal Net (1915 to 31
      January 2012), China National Knowledge Infrastructure (1915 to 31 January 2012),
      WanFang Database (1980 to 31 January 2012), Chinese Clinical Trial Registry (31
      January 2012), EMBASE (1980 to 31 January 2012), CINAHL (31 January 2012), PubMed
      (1980 to 31 January 2012), Wiley InterScience (1966 to 31 January 2012),
      International Clinical Trials Registry Platform (31 January 2012) and reference
      lists of retrieved studies. We also contacted organisations, individual experts
      working in the field, and medicinal herb manufacturers. SELECTION CRITERIA:
      Randomised or quasi-randomised controlled trials that compared Chinese herbal
      medicines (alone or combined with other pharmaceuticals) with placebo, no
      treatment (including bed rest), or other pharmaceuticals as treatments for
      threatened miscarriage. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed all the studies for inclusion in the review, assessed risk
      of bias and extracted the data. Data were checked for accuracy. MAIN RESULTS: In
      total, we included 44 randomised clinical trials with 5100 participants in the
      review.We did not identify any trials which used placebo or no treatment
      (including bed rest) as a control.The rate of effectiveness (continuation of
      pregnancy after 28 weeks of gestation) was not significantly different between
      the Chinese herbal medicines alone group compared with the group of women
      receiving Western medicines alone (average risk ratio (RR) 1.23; 95% confidence
      interval (CI) 0.96 to 1.57; one trial, 60 women).Chinese herbal medicines
      combined with Western medicines were more effective than Western medicines alone
      to continue the pregnancy beyond 28 weeks of gestation (average RR 1.28; 95% CI
      1.18 to 1.38; five trials, 550 women). AUTHORS' CONCLUSIONS: There was
      insufficient evidence to assess the effectiveness of Chinese herbal medicines
      alone for treating threatened miscarriage.A combination of Chinese herbal and
      Western medicines was more effective than Western medicines alone for treating
      threatened miscarriage. However, the quality of the included studies was poor.
      More high quality studies are necessary to further evaluate the effectiveness of
      Chinese herbal medicines for threatened miscarriage.

PMID- 22592731
TI  - Pacing for drug-refractory or drug-intolerant hypertrophic cardiomyopathy.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a genetic disease with an
      autosomal-dominant inheritance for which negative inotropes are the most widely
      used initial therapies. Observational studies and small randomised trials have
      suggested symptomatic and functional benefits using pacing and several theories
      have been put forward to explain why. Pacing, although not the primary treatment
      for HCM, could be beneficial to patients with relative or absolute
      contraindications to surgery or alcohol ablation. Several randomised controlled
      trials comparing pacing to other therapeutic modalities have been conducted but
      no Cochrane-style systematic review has been done. OBJECTIVES: To assess the
      effects of pacing in drug-refractory or drug-intolerant hypertrophic
      cardiomyopathy patients. SEARCH METHODS: We searched the following on the
      14/4/2010: CENTRAL (The Cochrane Library 2010, Issue 1), MEDLINE OVID (from 1950
      onwards ), EMBASE OVID (from 1980 onwards ), Web of Science with Conference
      Proceedings (from 1970 onwards). No language restrictions were applied. SELECTION
      CRITERIA: Randomised controlled trials of either parallel or crossover design
      that assess the beneficial and harmful effects of pacing for hypertrophic
      cardiomyopathy were included. When crossover studies were identified, we
      considered data only from the first phase. DATA COLLECTION AND ANALYSIS: Data
      from included studies were extracted onto a pre-formed data extraction paper by
      two authors independently. Data was then entered into Review Manager 5.1 for
      analysis. Risk of bias was assessed using the guidance provided in the Cochrane
      Handbook. For dichotomous data, relative risk was calculated; and for continuous
      data, the mean differences were calculated. Where appropriate data were
      available, meta-analysis was performed. Where meta-analysis was not possible, a
      narrative synthesis was written. A QUROUM flow chart was provided to show the
      flow of papers. MAIN RESULTS: Five studies (reported in 10 papers) were
      identified. However, three of the five studies provided un-usable data. Thus the
      data from only two studies (reported in seven papers) with 105 participants were
      included for this review. There was insufficient data to compare results on all
      cause mortality, cost effectiveness, exercise capacity, Quality of life and Peak
      O2 consumption.When comparing active pacing versus placebo pacing on exercise
      capacity, one study showed that exercise time decreased from (13.1 +/- 4.4)
      minutes to (12.6 +/- 4.3) minutes in the placebo group and increased from (12.1
      +/- 5.6) minutes to (12.9 +/- 4.2) minutes in the treatment group (MD 0.30; 95%
      CI -1.54 to 2.14). Statistically significant data from the same study showed that
      left ventricular outflow tract obstruction decreased from (71 +/- 32) mm Hg to
      (52 +/- 34) mm Hg in the placebo group and from (70 +/- 24) mm Hg to (33 +/- 27)
      mm Hg in the active pacing group (MD -19.00; 95% CI -32.29 to -5.71). This study
      was also able to show that New York Heart Association (NYHA) functional class
      decreased from (2.5 +/- 0.5) to (2.2 +/- 0.6) in the inactive pacing group and
      decreased from (2.6 +/- 0.5) to (1.7 +/- 0.7) in the placebo group (MD -0.50; 95%
      CI -0.78 to -0.22).When comparing active pacing versus trancoronary ablation of
      septal hypertrophy (TASH), data from one study showed that NYHA functional class
      decreased from (3.2 +/- 0.7) to (1.5 +/- 0.5) in the TASH group and decreased
      from (3.0 +/- 0.1) to (1.9 +/- 0.6) in the pacemaker group. This study also
      showed that LV wall thickness remained unchanged in the active pacing group
      compared to reduction from (22 +/- 4) mm to (17 +/- 3) mm in the TASH group (MD
      0.60; 95% CI -5.65 to 6.85) and that LV outflow tract obstruction decreased from
      (80 +/- 35.5) mm Hg in the TASH group to (49.3 +/- 37.7) mm Hg in the pacemaker
      group. AUTHORS' CONCLUSIONS: Trials published to date lack information on
      clinically relevant end-points. Existing data is derived from small trials at
      high risk of bias, which concentrate on physiological measures. Their results are
      inconclusive. Further large and high quality trials with more appropriate
      outcomes are warranted.

PMID- 22592732
TI  - Beta2-adrenoceptor agonists for dysmenorrhoea.
AB  - BACKGROUND: Dysmenorrhoea is a common gynaecological complaint that can affect as
      many as 50% of premenopausal women, 10% of whom suffer severely enough to be
      rendered incapacitated for one to three days during each menstrual cycle. Primary
      dysmenorrhoea is where women suffer from menstrual pain but lack any pathology in
      their pelvic anatomy. Beta2-adrenoceptor agonists have been used in the treatment
      of women with primary dysmenorrhoea but their effects are unclear. OBJECTIVES: To
      determine the effectiveness and safety of beta2-adrenoceptor agonists in the
      treatment of primary dysmenorrhoea. SEARCH METHODS: We searched the Cochrane
      Menstrual Disorders and Subfertility Group Specialised Register; CENTRAL (The
      Cochrane Library 2011, Issue 8); MEDLINE; EMBASE; PsycINFO and the EBM Reviews
      databases. The last search was on 22 August 2011. SELECTION CRITERIA: Randomised
      controlled trials comparing beta2-adrenoceptor agonists with placebo or no
      treatment, each other or any other conventional treatment in women of
      reproductive age with primary dysmenorrhoea. DATA COLLECTION AND ANALYSIS: Two
      review authors independently assessed trial quality and extracted the data. MAIN
      RESULTS: Five trials involving 187 women with an age range of 15 to 40 years were
      included. Oral isoxsuprine was compared with placebo in two trials; terbutaline
      oral spray, ritodrine chloride and oral hydroxyphenyl-orciprenalin were compared
      with placebo in a further three trials. Clinical diversity in the studies in
      terms of the interventions being evaluated, assessments at different time points
      and the use of different assessment tools mitigated against pooling of outcome
      data across studies in order to provide a summary estimate of effect for any of
      the comparisons. Only one study, with unclear risk of bias, reported pain relief
      with a combination of isoxsuprine, acetaminophen and caffeine. None of the other
      studies reported any significant clinical difference in effectiveness between the
      intervention and placebo. Adverse effects were reported with all of these
      medications in up to a quarter of the total number of participants. They included
      nausea, vomiting, dizziness, quivering, tremor and palpitations. AUTHORS'
      CONCLUSIONS: The evidence presented in this review was based on a few relatively
      small-sized studies that were categorised to have unclear to high risk of bias,
      which does not allow confident decision-making at present about the use of beta2
      adrenoceptor agonists for dysmenorrhoea. The benefits as reported in one study
      should be balanced against the wide array of unacceptable side effects documented
      with this class of medication. We have emphasised the lack of precision and
      limitations in the reported data where appropriate.

PMID- 22592733
TI  - Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with
      glucocorticoid therapy for childhood acute lymphoblastic leukaemia.
AB  - BACKGROUND: Glucocorticoids play a major role in the treatment of acute
      lymphoblastic leukaemia (ALL). However, supraphysiological doses may cause
      suppression of the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis
      suppression resulting in reduced cortisol response may cause an impaired stress
      response and an inadequate host defence against infections, which remains a cause
      of morbidity and death. The exact occurrence and duration of HPA axis suppression
      after glucocorticoid therapy for childhood ALL are unclear. OBJECTIVES: To
      examine the occurrence and duration of HPA axis suppression after (each cycle of)
      glucocorticoid therapy for childhood ALL. SEARCH METHODS: We searched the
      Cochrane Central Register of Controlled Trials (in The Cochrane Library, issue 3,
      2010), MEDLINE/PubMed (from 1945 to July 2010) and EMBASE/Ovid (from 1980 to July
      2010). In addition, we searched reference lists of relevant articles, conference
      proceedings and ongoing trial databases. SELECTION CRITERIA: All study designs,
      except case reports and patient series with fewer than 10 patients, examining the
      effect of glucocorticoid therapy for childhood ALL on the HPA axis function. DATA
      COLLECTION AND ANALYSIS: Two review authors independently performed the study
      selection. One review author performed the data extraction and 'Risk of bias'
      assessment, which was checked by another review author. MAIN RESULTS: We
      identified seven studies (total number of participants = 189), including one
      randomised controlled trial (RCT), which assessed the adrenal function. None of
      the studies assessed the HPA axis at the level of the hypothalamus, pituitary, or
      both. Due to substantial differences between studies, results could not be
      pooled. All studies had some methodological limitations. The included studies
      demonstrated that adrenal insufficiency occurs in nearly all patients in the
      first days after cessation of glucocorticoid treatment for childhood ALL. The
      majority of patients recovered within a few weeks, but a small amount of patients
      had ongoing adrenal insufficiency lasting up to 34 weeks. In the RCT, the
      occurrence and duration of adrenal insufficiency did not differ between the
      prednisolone and dexamethasone arms. In one study included in the review it
      appeared that treatment with fluconazole prolonged the duration of adrenal
      insufficiency. AUTHORS' CONCLUSIONS: Based on the available evidence, we conclude
      that adrenal insufficiency commonly occurs in the first days after cessation of
      glucocorticoid therapy for childhood ALL, but the exact duration is unclear.
      Since no data on the level of the hypothalamus and the pituitary were available
      we cannot make any conclusions regarding those outcomes. Clinicians should
      consider prescribing glucocorticoid replacement therapy during periods of serious
      stress in the first weeks after cessation of glucocorticoid therapy for childhood
      ALL, to reduce the risk of life-threatening complications. However, more high
      quality research is needed for evidence-based guidelines for glucocorticoid
      replacement therapy.Special attention should be paid to patients receiving
      fluconazole therapy, and perhaps similar antifungal drugs, as this may prolong
      the duration of adrenal insufficiency.

PMID- 22592734
TI  - Oral traditional Chinese medication for adhesive small bowel obstruction.
AB  - BACKGROUND: Small bowel obstruction (SBO) is one of the most common emergent
      complications of general surgery. Intra-abdominal adhesions are the leading cause
      of SBO. Because surgery can induce new adhesions, non-operative management is
      preferred in the absence of signs of peritonitis or strangulation. Oral
      traditional Chinese herbal medicine has long been used as a non-operative therapy
      to treat adhesive SBO in China. Many controlled trials have been conducted to
      investigate its therapeutic value in resolving adhesive SBO. OBJECTIVES: The aim
      of this review was to assess the efficacy and safety of oral traditional Chinese
      medicine (TCM) for adhesive small bowel obstruction. SEARCH METHODS: We searched
      the following databases, without regard to language or publishing restrictions:
      the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE,
      Chinese Biomedical Database (CBM), China National Knowledge
      Infrastructure/Chinese Academic Journals full-text Database (CNKI), and VIP (a
      full-text database of Chinese journals). The searches were conducted in November
      2011. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised
      controlled trials comparing Chinese medicines administered orally, via the
      gastric canal, or both with a placebo or conventional therapy in participants
      diagnosed with adhesive SBO were considered. We also considered trials of TCM
      (oral administration, gastric tube perfusion, or both) plus conventional therapy
      compared with conventional therapy alone for patients with adhesive SBO. Studies
      addressing the safety and efficacy of oral traditional Chinese medicinal agents
      in the treatment of adhesive SBO were also considered. DATA COLLECTION AND
      ANALYSIS: Two authors collected the data independently. We assessed the risk of
      bias according to the following methodological criteria: random sequence
      generation, allocation concealment, blinding, incomplete outcome data, selective
      outcome reporting and other sources of bias. Dichotomous data are presented as
      risk ratios (OR) and 95% confidence intervals (CI); continuous outcomes are
      presented as mean differences (MD) and 95% CIs. The data analyses were carried
      out using Review Manager 5.1. For cases in which necessary information was not
      reported in the paper, we contacted the primary authors for additional
      information. MAIN RESULTS: Five randomised trials involving 664 participants were
      analysed. Five different herbal medicines were tested in these trials, including
      Huo-Xue-Tong-Fu decoction, Xiao-Cheng-Qi-Tang decoction, a combination of Xiao
      Cheng-Qi-Tang and Si-Jun-Zi-Tang decoctions, Chang-Nian-Lian-Song-Jie-Tang
      decoction, and Fufang-Da-Cheng-Qi-Tang decoction. There were variations in the
      tested herbal compositions and methods of medicine administration. The main
      outcomes reported in the trials were effects on abdominal pain, abdominal
      distension, constipation defection, time of first defecation after treatment, and
      reoperation rate during the course of the disease. Secondary outcomes selected
      for this review were not available, including complications such as small bowel
      perfusion (bowel resection, system complications, and other possible
      complications), length of hospital stay, cost of hospitalisation, and time from
      admission to surgical intervention. The results of five trials showed that
      patients receiving TCM combined with conventional therapy seemed to have improved
      outcomes compared with patients receiving conventional treatment alone (OR 4.24,
      95% CI 2.83 to 6.36).However, we cannot conclusively determine the efficacy of
      TCM in this review due to inadequate reporting, low methodological quality, and
      the prevalence of various biases in the reviewed studies. Furthermore, because
      none of the reviewed trials discussed adverse events, we could not evaluate the
      safety of TCM for adhesive SBO patients. All trials were conducted and published
      in China. AUTHORS' CONCLUSIONS: Although many studies have assessed the use of
      TCM products for adhesive SBO, most were excluded from this review due to their
      methodological limitations. This systematic review did not find sufficient
      evidence to support the objective efficacy and safety of TCM for patients with
      adhesive SBO. The positive evidence should be interpreted with caution given the
      insufficient number of studies with large sample sizes, the absence of well
      designed, high-quality trials, and the lack of safety information. Therefore,
      further studies with larger sample sizes and high-quality, randomised, and
      controlled trials are necessary to produce more accurate and meaningful data on
      the efficacy of Chinese herbal medicines for adhesive SBO.

PMID- 22592735
TI  - Aripiprazole for autism spectrum disorders (ASD).
AB  - BACKGROUND: Autism spectrum disorders (ASD) include Autistic Disorder, Asperger's
      Disorder and Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS).
      Irritability related to ASD has been treated with antipsychotics. Aripiprazole, a
      third generation atypical antipsychotic, is a relatively new drug that has a
      unique mechanism of action different from other antipsychotics. OBJECTIVES: To
      determine the safety and efficacy of aripiprazole for individuals with ASD.
      SEARCH METHODS: We searched the following databases on 4th May 2011: Cochrane
      Central Register of Controlled Trials (CENTRAL) (2011, Issue 2), MEDLINE (1948 to
      April Week 3 2011), EMBASE (1980 to 2011 Week 17), PsycINFO (1887 to current),
      CINAHL (1937 to current), WorldCat, ZETOC, Autism Data, Conference Proceedings
      Index-S, Conference Proceedings Index -SSH, ClinicalTrials.gov, and WHO ICTRP. We
      searched for records published in 1990 or later, as this was the year
      aripiprazole became available. SELECTION CRITERIA: Randomized controlled trials
      of aripiprazole versus placebo for the treatment of individuals with a diagnosis
      of ASD. DATA COLLECTION AND ANALYSIS: Two review authors independently collected,
      evaluated, and analyzed data. We performed meta-analysis for primary and
      secondary outcomes, when possible. MAIN RESULTS: Two randomized controlled trials
      with similar methodology have evaluated the use of aripiprazole for a duration of
      eight weeks in 316 children with ASD. The included trials had a low risk of bias.
      Although we searched for studies across age groups, only studies in children and
      youths were found. Meta-analysis of study results revealed a mean improvement of
      6.17 points on the Aberrant Behavior Checklist (ABC) irritability subscale, 7.93
      points on the ABC hyperactivity subscale, and 2.66 points in the stereotypy
      subscale in children treated with aripiprazole relative to children treated with
      a placebo. In terms of adverse side effects, children treated with aripiprazole
      had a greater increase in weight with a mean increase of 1.13 kg relative to
      placebo, and had a higher risk ratio for sedation (RR 4.28) and tremor (RR
      10.26). AUTHORS' CONCLUSIONS: Evidence from two randomized controlled trials
      suggests that aripiprazole can be effective in treating some behavioral aspects
      of ASD in children. After treatment with aripiprazole, children showed less
      irritability, hyperactivity, and stereotypies (repetitive, purposeless actions).
      Notable side effects must be considered, however, such as weight gain, sedation,
      drooling, and tremor. Longer studies of aripiprazole in individuals with ASD
      would be useful to gain information on long-term safety and efficacy.

PMID- 22592736
TI  - Single crowns versus conventional fillings for the restoration of root filled
      teeth.
AB  - BACKGROUND: Endodontic treatment, involves removal of the dental pulp and its
      replacement by a root canal filling. Restoration of root filled teeth can be
      challenging due to structural differences between vital and non-vital root filled
      teeth. Direct restoration involves placement of a restorative material e.g.
      amalgam or composite directly into the tooth. Indirect restorations consist of
      cast metal or ceramic (porcelain) crowns. The choice of restoration depends on
      the amount of remaining tooth which may influence long term survival and cost.
      The comparative in service clinical performance of crowns or conventional
      fillings used to restore root filled teeth is unclear. OBJECTIVES: To assess the
      effects of restoration of endodontically treated teeth (with or without post and
      core) by crowns versus conventional filling materials. SEARCH METHODS: We
      searched the following databases: the Cochrane Oral Health Group's Trials
      Register, CENTRAL, MEDLINE via OVID, EMBASE via OVID, CINAHL via EBSCO, LILACS
      via BIREME and the reference lists of articles as well as ongoing trials
      registries.There were no restrictions regarding language or date of publication.
      Date of last search was 13 February 2012. SELECTION CRITERIA: Randomised
      controlled trials (RCTs) or quasi-randomised controlled trials in participants
      with permanent teeth which have undergone endodontic treatment. Single full
      coverage crowns compared with any type of filling materials for direct
      restoration, as well as indirect partial restorations (e.g. inlays and onlays).
      Comparisons considered the type of post and core used (cast or prefabricated
      post), if any. DATA COLLECTION AND ANALYSIS: Two review authors independently
      assessed trial quality and extracted data. MAIN RESULTS: One trial judged to be
      at high risk of bias due to missing outcome data, was included. 117 participants
      with a root filled premolar tooth restored with a carbon fibre post, were
      randomised to either a full coverage metal-ceramic crown or direct adhesive
      composite restoration. At 3 years there was no reported difference between the
      non-catastrophic failure rates in both groups. Decementation of the post and
      marginal gap formation occurred in a small number of teeth. AUTHORS' CONCLUSIONS:
      There is insufficient evidence to support or refute the effectiveness of
      conventional fillings over crowns for the restoration of root filled teeth. Until
      more evidence becomes available clinicians should continue to base decisions on
      how to restore root filled teeth on their own clinical experience, whilst taking
      into consideration the individual circumstances and preferences of their
      patients.

PMID- 22592737
TI  - Medical interventions for the prevention of platinum-induced hearing loss in
      children with cancer.
AB  - BACKGROUND: Platinum-based therapy, including cisplatin, carboplatin and/or
      oxaliplatin, is used to treat a variety of paediatric malignancies.
      Unfortunately, one of the most important adverse effects is the occurrence of
      hearing loss or ototoxicity. In an effort to prevent this ototoxicity, different
      otoprotective medical interventions have been studied. OBJECTIVES: The primary
      objective was to assess the efficacy of different otoprotective medical
      interventions in preventing hearing loss in children with cancer treated with
      platinum-based therapy. Secondary objectives were to determine possible effects
      of these interventions on anti-tumour efficacy, toxicities other than hearing
      loss and quality of life. SEARCH METHODS: We searched the electronic databases
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library
      2011, Issue 4), MEDLINE (PubMed) (1945 to 22 December 2011) and EMBASE (Ovid)
      (1980 to 22 December 2011). In addition, we handsearched reference lists of
      relevant articles and the conference proceedings of the International Society for
      Paediatric Oncology (2006 to 2011), the American Society of Pediatric
      Hematology/Oncology (2007 to 2011) and the International Conference on Long-Term
      Complications of Treatment of Children and Adolescents for Cancer (2010). We
      scanned the International Standard Randomized Controlled Trial Number (ISRCTN)
      Register and the National Institute of Health Register for ongoing trials
      (www.controlled-trials.com) (searched on 20 December 2011). SELECTION CRITERIA:
      Randomized controlled trials (RCTs) or controlled clinical trials (CCTs)
      evaluating platinum-based therapy together with an otoprotective medical
      intervention versus platinum-based therapy with placebo, no additional treatment
      or another protective medical intervention in children with cancer. DATA
      COLLECTION AND ANALYSIS: Two review authors independently performed the study
      selection, risk of bias assessment of included studies and data extraction,
      including adverse effects. Analyses were performed according to the guidelines of
      the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: We
      identified two RCTs and one CCT (total number of patients 149) evaluating the use
      of amifostine versus no additional treatment. Two studies included children with
      osteosarcoma, the other study included children with hepatoblastoma. Patients
      received cisplatin only or a combination of cisplatin and carboplatin, either
      administered intra-arterially or intravenously. All studies had methodological
      limitations. Unfortunately, pooling of the results of included studies was not
      possible. However, in all individual studies no significant difference was
      identified in symptomatic ototoxicity only (that is grade 2 or higher) and
      combined asymptomatic and symptomatic ototoxicity (that is grade 1 or higher)
      between children treated with or without amifostine. Only one study, including
      children with osteosarcoma treated with intra-arterial cisplatin, provided
      information on tumour response, defined as the number of patients with a good or
      partial remission. The 'available data' analysis (data were missing for one
      patient), 'best case scenario' analysis and 'worst case scenario' analysis all
      showed a difference in favour of amifostine, but this difference was significant
      only in the 'worst case scenario' analysis (P = 0.04). No information on survival
      was available for any of the included study populations. Only one study,
      including children with osteosarcoma treated with intra-arterial cisplatin,
      provided data on the number of patients with adverse effects other than
      ototoxicity grade 3 or higher. There was a significant difference in favour of
      the control group in the occurrence of vomiting grade 3 or 4 (RR 9.04; 95% CI
      1.99 to 41.12; P = 0.004). No significant difference was identified between
      treatment groups for cardiotoxicity and renal toxicity grade 3 or 4. None of the
      studies evaluated quality of life. No eligible studies were found for possible
      otoprotective medical interventions other than amifostine and other types of
      malignancies. AUTHORS' CONCLUSIONS: At the moment there is no evidence from
      individual studies in children with osteosarcoma and hepatoblastoma treated with
      different platinum analogues and dosage schedules which underscores the use of
      amifostine as an otoprotective intervention as compared to no additional
      treatment. Since pooling of results was not possible and all studies had serious
      methodological limitations, no definitive conclusions can be made. It should be
      noted that 'no evidence of effect', as identified in this review, is not the same
      as 'evidence of no effect'. Based on the currently available evidence, we are not
      able to give recommendations for clinical practice. For other possible
      otoprotective medical interventions and other types of malignancies no eligible
      studies were identified, so no conclusions can be made about their efficacy in
      preventing ototoxicity in children treated with platinum-based therapy. More high
      quality research is needed.

PMID- 22592738
TI  - Oxytocin augmentation of labour in women with epidural analgesia for reducing
      operative deliveries.
AB  - BACKGROUND: The rate of operative deliveries (both caesarean sections, vacuum
      extractions and forceps), continues to rise throughout the world. These are
      associated with significant maternal and neonatal morbidity. The most common
      reasons for operative births in nulliparous women are labour dystocia (failure to
      progress), and non-reassuring fetal status. Epidural analgesia has been shown to
      slow the progress of labour, as well as increase the rate of instrumental
      deliveries. However, it is unclear whether the use of oxytocin in women with
      epidural analgesia results in a reduction in operative deliveries, and thereby
      reduces both maternal and fetal morbidity. OBJECTIVES: To determine whether
      augmentation of women using epidural analgesia with oxytocin will decrease the
      incidence of operative deliveries and thereby reduce fetal and maternal
      morbidity. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth
      Group's Trials Register (29 February 2012). SELECTION CRITERIA: All published and
      unpublished randomised and quasi-randomised trials that compared augmentation
      with oxytocin of women in spontaneous labour with epidural analgesia versus
      intent to manage expectantly were included. Cluster-randomised trials were
      eligible for inclusion but none were identified.Cross-over study designs were
      unlikely to be relevant for this intervention, and we planned to exclude them if
      any were identified. We did not include results that were only available in
      published abstracts. DATA COLLECTION AND ANALYSIS: The two review authors
      independently assessed for inclusion the 16 studies identified as a result of the
      search strategy. Both review authors independently assessed the risk of bias for
      each included study. Both review authors independently extracted data. Data were
      checked for accuracy. MAIN RESULTS: We included two studies, involving 319 women.
      There was no statistically significant difference between the two groups in
      either of the primary outcomes of caesarean section (risk ratio (RR) 0.95, 95%
      confidence interval (CI) 0.42 to 2.12) or instrumental delivery (RR 0.88, 95% CI
      0.72 to 1.08). Similarly, there were no statistically significant differences
      between the two groups in any of the secondary outcomes for which data were
      available. This included Apgar score less than seven at five minutes (RR 3.06,
      0.13 to 73.33), admission to neonatal intensive care unit (RR 1.07, 95% CI 0.29
      to 3.93), uterine hyperstimulation (RR 1.32, 95% CI 0.97 to 1.80) and postpartum
      haemorrhage (RR 0.96, 95% CI 0.58, 1.59). AUTHORS' CONCLUSIONS: There was no
      statistically significant difference identified between women in spontaneous
      labour with epidural analgesia who were augmented with oxytocin, compared with
      those who received placebo. However, due to the limited number of women included
      in the studies, further research in the form of randomised controlled trials are
      required.

PMID- 22592739
TI  - Antibiotic treatment for Stenotrophomonas maltophilia in people with cystic
      fibrosis.
AB  - BACKGROUND: Stenotrophomonas maltophilia is one of the most common emerging multi
      drug resistant organisms found in the lungs of people with cystic fibrosis and
      its prevalence is increasing. Chronic infection with Stenotrophomonas maltophilia
      has recently been shown to be an independent predictor of pulmonary exacerbation
      requiring hospitalization and antibiotics. However, the role of antibiotic
      treatment of Stenotrophomonas maltophilia infection in people with cystic
      fibrosis is still unclear. OBJECTIVES: The objective of our review is to assess
      the effectiveness of antibiotic treatment for Stenotrophomonas maltophilia in
      people with cystic fibrosis. The primary objective is to assess this in relation
      to lung function and pulmonary exacerbations in the setting of acute pulmonary
      exacerbations. The secondary objective is to assess this in relation to the
      eradication of Stenotrophomonas maltophilia. SEARCH METHODS: We searched the
      Cochrane Cystic Fibrosis Trials Register, compiled from electronic database
      searches and handsearching of journals and conference abstract books. We also
      searched a registry of ongoing trials and the reference lists of relevant
      articles and reviews.Date of latest search: 06 July 2011. SELECTION CRITERIA: Any
      randomized controlled trial of Stenotrophomonas maltophilia mono-infection or
      Stenotrophomonas maltophilia co-infection with Pseudomonas aeruginosa in either
      the setting of an acute pulmonary exacerbation or a chronic infection treated
      with suppressive antibiotic therapy. DATA COLLECTION AND ANALYSIS: Both authors
      independently assessed the trials identified by the search for potential
      inclusion in the review. MAIN RESULTS: The initial search strategy identified
      only one study of antibiotic treatment of pulmonary exacerbations that included
      cystic fibrosis patients with Stenotrophomonas maltophilia. However, this study
      had to be excluded because data was not available per pathogen. AUTHORS'
      CONCLUSIONS: This review did not identify any evidence regarding the
      effectiveness of antibiotic treatment for Stenotrophomonas maltophilia in people
      with cystic fibrosis. Until such evidence becomes available, clinicians need to
      use their clinical judgement as to whether or not to treat Stenotrophomonas
      maltophilia infection in patients with cystic fibrosis. Randomized clinical
      trials are needed to address these unanswered clinical questions.

PMID- 22592740
TI  - Inspiratory muscle training for the recovery of function after stroke.
AB  - BACKGROUND: Inspiratory muscle weakness has been observed in patients with
      stroke. Inspiratory muscle training is an intervention that has shown possible
      effects for functional recovery of patients with stroke. OBJECTIVES: To
      investigate the effect and safety of inspiratory muscle training for improving
      activities of daily living, respiratory muscle function, quality of life and
      cardiorespiratory fitness after stroke. SEARCH METHODS: We searched the Cochrane
      Stroke Group's Trials Register (August 2011), the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2011, October Issue 4), MEDLINE
      (1948 to October 2011), EMBASE (1974 to October 2011), CINAHL (1982 to October
      2011), AMED (1985 to October 2011), PEDro (October 2011) and four Chinese
      databases. In an effort to identify further published, unpublished and ongoing
      trials, we searched ongoing trials registers and conference proceedings, checked
      reference lists, and contacted authors of relevant studies and training devices
      manufactures. There were no language restrictions. SELECTION CRITERIA: Randomised
      controlled trials (RCTs) comparing inspiratory muscle training with no
      intervention, sham inspiratory muscle training or other cardiorespiratory
      training for patients with stroke were eligible. DATA COLLECTION AND ANALYSIS:
      Two review authors independently assessed trial quality and extracted data. The
      primary outcomes were activities of daily living and respiratory muscle strength;
      the secondary outcomes were quality of life, cardiorespiratory fitness and
      adverse effects. MAIN RESULTS: We included two trials involving a total of 66
      patients in this review. Pooling analyses of data was not possible due to
      considerable heterogeneity between the trials and a lack of data in both trials.
      One study found a significant increase in respiratory muscle strength favouring
      inspiratory muscle training over sham inspiratory muscle training, but there was
      no significant difference between groups on quality of life. The other study
      showed that patients receiving inspiratory muscle training were more likely to
      improve their activities of daily living, quality of life and cardiorespiratory
      fitness than those patients who received no intervention. However, the main
      results were not compared directly with breathing retraining. Furthermore,
      neither of the trials assessed the safety and tolerance of inspiratory muscle
      training. AUTHORS' CONCLUSIONS: There is insufficient evidence to support
      inspiratory muscle training as an effective treatment to improve function after
      stroke, and no evidence relating to the safety of inspiratory muscle training.
      Further well-designed RCTs are required.

PMID- 22592741
TI  - Phenytoin for neuropathic pain and fibromyalgia in adults.
AB  - BACKGROUND: Antiepileptic drugs have been used in pain management since the
      1960s; some have shown efficacy in treating different neuropathic pain
      conditions. Phenytoin is an established antiepileptic drug that has been used
      occasionally to treat intractable trigeminal neuralgia. OBJECTIVES: To assess the
      analgesic efficacy and adverse effects of the antiepileptic drug phenytoin in
      neuropathic pain and fibromyalgia. SEARCH METHODS: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue
      2), MEDLINE, and EMBASE to 28 February 2012, together with reference lists of
      retrieved papers and reviews, and ClinicalTrials.gov. SELECTION CRITERIA: We
      planned to include randomised, double-blind studies of eight weeks duration or
      longer, comparing phenytoin with placebo or another active treatment in chronic
      neuropathic pain or fibromyalgia. DATA COLLECTION AND ANALYSIS: Two review
      authors would independently extract data for efficacy and adverse events, and
      examine issues of study quality. MAIN RESULTS: We did not identify any studies
      that satisfied the inclusion criteria. AUTHORS' CONCLUSIONS: This review
      uncovered no evidence of sufficient quality to support the use of phenytoin in
      chronic neuropathic pain or fibromyalgia.

PMID- 22592742
TI  - Clonazepam for neuropathic pain and fibromyalgia in adults.
AB  - BACKGROUND: Antiepileptic drugs have been used in pain management since the
      1960s; some have shown efficacy in treating different neuropathic pain
      conditions. Clonazepam, a benzodiazepine, is an established antiepileptic drug,
      but its place in the treatment of neuropathic pain is unclear. OBJECTIVES: To
      assess the analgesic efficacy and adverse effects of the antiepileptic drug
      clonazepam in neuropathic pain and fibromyalgia. SEARCH METHODS: We searched the
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library
      2012, Issue 2). MEDLINE, and EMBASE to 28 February 2012, together with reference
      lists of retrieved papers and reviews, and ClinicalTrials.gov. SELECTION
      CRITERIA: We planned to include randomised, double-blind studies of eight weeks
      duration or longer, comparing clonazepam with placebo or another active treatment
      in chronic neuropathic pain or fibromyalgia. DATA COLLECTION AND ANALYSIS: Two
      review authors would independently extract data for efficacy and adverse events,
      and examine issues of study quality. MAIN RESULTS: We did not identify any
      studies that satisfied the inclusion criteria. AUTHORS' CONCLUSIONS: This review
      uncovered no evidence of sufficient quality to support the use of clonazepam in
      chronic neuropathic pain or fibromyalgia.

PMID- 22592743
TI  - Early routine endoscopic retrograde cholangiopancreatography strategy versus
      early conservative management strategy in acute gallstone pancreatitis.
AB  - BACKGROUND: The role and timing of endoscopic retrograde cholangiopancreatography
      (ERCP) in acute gallstone pancreatitis remains controversial. A number of
      clinical trials and meta-analyses have provided conflicting evidence. OBJECTIVES:
      To systematically review evidence from randomized controlled trials (RCTs)
      assessing the clinical effectiveness and safety of the early routine ERCP
      strategy compared to the early conservative management with or without selective
      use of ERCP strategy, based on all important, clinically relevant and
      standardized outcomes including mortality, local and systemic complications as
      defined by the Atlanta Classification (Bradley 1993) and by authors of the
      primary study, and ERCP-related complications in unselected patients with acute
      gallstone pancreatitis. SEARCH METHODS: We searched the CENTRAL (The Cochrane
      Library), MEDLINE, EMBASE, and LILACS databases and major conference proceedings
      up to January 2012, using the Cochrane Upper Gastrointestinal and Pancreatic
      Diseases model with no language restrictions. SELECTION CRITERIA: RCTs comparing
      the early routine ERCP strategy versus the early conservative management with or
      without selective use of ERCP strategy in patients with suspected acute gallstone
      pancreatitis. We included studies in which the population with acute gallstone
      pancreatitis was a subgroup within a larger group of patients. We only included
      studies involving only a selected subgroup of patients with acute gallstone
      pancreatitis (actual severe pancreatitis) in subgroup analyses. DATA COLLECTION
      AND ANALYSIS: Two review authors conducted study selection, data extraction, and
      methodological quality assessment independently. Using intention-to-treat
      analysis with random-effects models, we combined dichotomous data to obtain risk
      ratios (RR) with 95% confidence intervals (CI). We assessed heterogeneity using
      the Chi2 test and I2 statistic. To explore sources of heterogeneity, we conducted
      a priori subgroup analyses according to predicted severity of pancreatitis,
      cholangitis, biliary obstruction, time to ERCP in routine ERCP strategy, use of
      selective ERCP in conservative management strategy, and risk of bias. To assess
      the robustness of our results, we carried out sensitivity analyses using
      different summary statistics (RR versus odds ratio (OR)) and meta-analytic models
      (fixed versus random-effects), and per-protocol analysis. We performed influence
      analysis by exclusion of each study. MAIN RESULTS: Five RCTs comprising 644
      participants were included in the main analyses. Two additional RCTs, comprising
      only patients with actual severe acute gallstone pancreatitis, were included only
      in subgroup analyses. There was statistical heterogeneity among trials for
      mortality, but not for other outcomes. In unselected patients with acute
      gallstone pancreatitis, there were no statistically significant differences
      between the two strategies in mortality (RR 0.74, 95% CI 0.18 to 3.03), local and
      systemic complications as defined by the Atlanta Classification (RR 0.86, 95% CI
      0.52 to 1.43; and RR 0.59, 95% CI 0.31 to 1.11 respectively) and by authors of
      the primary study (RR 0.80, 95% CI 0.51 to 1.26; and RR 0.76, 95% CI 0.53 to 1.09
      respectively). The results were robust to sensitivity and influence analyses
      except for systemic complications as defined by the Atlanta Classification. There
      was no evidence to suggest that the results were dependent on predicted severity
      of pancreatitis. Among trials that included patients with cholangitis, the early
      routine ERCP strategy significantly reduced mortality (RR 0.20, 95% CI 0.06 to
      0.68), local and systemic complications as defined by the Atlanta Classification
      (RR 0.45, 95% CI 0.20 to 0.99; and RR 0.37, 95% CI 0.18 to 0.78 respectively) and
      by authors of the primary study (RR 0.50, 95% CI 0.29 to 0.87; and RR 0.41, 95%
      CI 0.21 to 0.82 respectively). Among trials that included patients with biliary
      obstruction, the early routine ERCP strategy was associated with a significant
      reduction in local complications as defined by authors of the primary study (RR
      0.54, 95% CI 0.32 to 0.91), and a non-significant trend towards reduction of
      local and systemic complications as defined by the Atlanta Classification (RR
      0.53, 95% CI 0.26 to 1.07; and RR 0.56, 95% CI 0.30 to 1.02 respectively) and
      systemic complications as defined by authors of the primary study (RR 0.59, 95%
      CI 0.35 to 1.01). ERCP complications were infrequent. AUTHORS' CONCLUSIONS: In
      patients with acute gallstone pancreatitis, there is no evidence that early
      routine ERCP significantly affects mortality, and local or systemic complications
      of pancreatitis, regardless of predicted severity. Our results, however, provide
      support for current recommendations that early ERCP should be considered in
      patients with co-existing cholangitis or biliary obstruction.

PMID- 22592744
TI  - The COMET (Core Outcome Measures in Effectiveness Trials) Initiative: Its Role in
      Improving Cochrane Reviews.

PMID- 22592745
TI  - Altered bone biology in psoriatic arthritis.
AB  - Psoriatic arthritis (PsA) is characterized by focal bone erosions mediated by
      osteoclasts at the bone-pannus junction. The bulk of research over the past
      decade has centered on mechanisms that underlie osteoclastogenesis along with new
      insights into osteoimmunology; however, recent advances that focus on steps that
      lead to new bone formation are beginning to emerge. New revelations about bone
      formation may have direct relevance to PsA given the presence of enthesophytes,
      syndesmophytes, and bony ankylosis frequently observed in patients with this
      disorder. In this review, we discuss current developments in the pathogenesis of
      new bone formation, novel imaging approaches to study bone remodeling and
      highlight innovative approaches to study the effect of inflammation on bone.
      Lastly, we discuss promising therapies that target joint inflammation and
      osteitis with the potential to mediate pathologic bone formation.

PMID- 22592746
TI  - Impact of psoriatic arthritis on the patient: through the lens of the WHO
      International Classification of Functioning, Health, and Disability.
AB  - Psoriatic arthritis is associated with a broad range of problems from the
      perspective of the patient. These include symptoms relating to skin and
      musculoskeletal disease to difficulties with day-to-day activities, social
      interactions, paid employment, and community participation. Additional problems
      related to frequent comorbidities impose further impact. It has been shown that
      individuals with psoriatic arthritis have similar or worse disability than men
      older than 75 years of age in the general population, and psoriatic arthritis
      confers worse health status than many other common chronic diseases. The World
      Health Organization International Classification of Functioning, Disability, and
      Health provides a useful framework for considering the impact of this disease.
      Ideal clinical management of psoriatic arthritis would provide access to an
      interdisciplinary team with expertise in functional, social, vocational, and
      community issues, as well as to medical expertise.

PMID- 22592748
TI  - Apocynin attenuates lipopolysaccharide-induced lung injury in an isolated and
      perfused rat lung model.
AB  - Apocynin (Apo) suppresses the generation of reactive oxygen species that are
      implicated in lipopolysaccharide (LPS)-induced lung injury (LPSLI). We thus
      hypothesized that Apo may attenuate LPSLI. In addition, we explored the cellular
      and molecular mechanisms of Apo treatment in LPSLI. Lipopolysaccharide-induced
      lung injury was induced by intratracheal instillation of 10 mg/kg LPS in isolated
      and perfused rat lung model. Apocynin was administered in the perfusate at 15 min
      before LPS was administered. Hemodynamics, lung injury indices, inflammatory
      responses, and activation of apoptotic pathways were assessed. There was an
      increase in lung vascular permeability associated with lung weight gain after LPS
      exposure. The levels of interleukin 1beta (IL-1beta), tumor necrosis factor alpha
      (TNF-alpha), macrophage inflammatory protein 2, H2O2, and albumin increased in
      the bronchoalveolar lavage fluid. Adhesion molecule of neutrophil (CD31) was
      upregulated. The expression of TNF-alpha, IL-1beta, glutathione, myeloperoxidase,
      JNK, P38, caspase 3, p-AKT, and plasminogen activator inhibitor 1 in lung tissue
      was greater in the LPS groups when compared with the control group. Upregulation
      and activation of nuclear factor kappaB occurred along with increased
      histopathologic lung injury score in LPSLI. The Apo attenuated these inflammatory
      responses including the levels of CD31, H2O2, TNF-alpha, IL-1beta,
      myeloperoxidase, P38, and nuclear factor kappaB along with downregulation of
      apoptosis as reflected by caspase 3 and p-AKT. In addition, Apo attenuated the
      increase in lung weight, bronchoalveolar lavage fluid albumin content, and the
      histopathologic lung injury score. In conclusion, LPSLI is associated with
      increased inflammatory responses, apoptosis, and coagulation. The administration
      of Apo attenuates LPSLI through downregulation of the inflammatory responses and
      apoptosis.

PMID- 22592747
TI  - Mechanisms of methicillin-resistant Staphylococcus aureus pneumonia-induced
      intestinal epithelial apoptosis.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia-induced sepsis is a
      common cause of morbidity in the intensive care unit. Although pneumonia is
      initiated in the lungs, extrapulmonary manifestations occur commonly. In light of
      the key role the intestine plays in the pathophysiology of sepsis, we sought to
      determine whether MRSA pneumonia induces intestinal injury. FVB/N mice were
      subjected to MRSA or sham pneumonia and killed 24 h later. Septic animals had a
      marked increase in intestinal epithelial apoptosis by both hematoxylin-eosin and
      active caspase 3 staining. Methicillin-resistant S. aureus-induced intestinal
      apoptosis was associated with an increase in the expression of the proapoptotic
      proteins Bid and Bax and the antiapoptotic protein Bcl-xL in the mitochondrial
      pathway. In the receptor-mediated pathway, MRSA pneumonia induced an increase in
      Fas ligand but decreased protein levels of Fas, FADD, pFADD, TNF-R1, and TRADD.
      To assess the functional significance of these changes, MRSA pneumonia was
      induced in mice with genetic manipulations in proteins in either the
      mitochondrial or receptor-mediated pathways. Both Bid-/- mice and animals with
      intestine-specific overexpression of Bcl-2 had decreased intestinal apoptosis
      compared with wild-type animals. In contrast, Fas ligand-/- mice had no
      alterations in apoptosis. To determine if these findings were organism-specific,
      similar experiments were performed in mice subjected to Pseudomonas aeruginosa
      pneumonia. Pseudomonas aeruginosa induced gut apoptosis, but unlike MRSA, this
      was associated with increased Bcl-2 and TNF-R1 and decreased Fas. Methicillin
      resistant S. aureus pneumonia thus induces organism-specific changes in
      intestinal apoptosis via changes in both the mitochondrial and receptor-mediated
      pathways, although the former may be more functionally significant.

PMID- 22592749
TI  - Lipid polymorphism in lyotropic liquid crystals for triggered release of
      bioactives.
AB  - In this review we present recent progress on lyotropic liquid crystals (LLC) as
      delivery vehicles for cosmetoceuticals, nutraceuticals, and drugs. LLC have been
      known for decades and their potential as delivery vehicles is well recognized.
      Yet, the two major mesophases, reverse hexagonal (H(II)) and bicontinuous cubic
      (primitive, gyroid, and diamond), are relatively hard gels with very slow release
      kinetics of the bioactives. In recent years a discontinuous cubic micellar
      mesophase (Q(L)) was characterized and studied, showing significant potential as
      a delivery vehicle. In addition, the H(II) mesophase formed could be much more
      fluid and produced at room temperature. Recent studies concentrated on
      establishing methods to evaluate solubilization capacity and relationship between
      the diameter and length of the cylinders and the nature of the solubilizates.
      Special attention was given to finding methods to target the vehicles to the
      lumen and to trigger the release of the bioactives. This review summarizes the
      efforts of our group along with work by numerous other scientists in this area.
      All these efforts suggest that the lyotropic mesophases and the corresponding
      dispersed soft particles (cubosomes, hexosomes, micellosomes) are now more than
      ever ready to become drug delivery vehicles for transport across the skin and the
      gut.

PMID- 22592750
TI  - A note to my younger colleagues. . .be brave.

PMID- 22592751
TI  - Shared decision-making and patient decision AIDS: is it time?

PMID- 22592752
TI  - Repeat revascularization is a faulty end point for clinical trials.

PMID- 22592754
TI  - Limitations of ranking lists based on cardiac surgery mortality rates.
AB  - BACKGROUND: Ranking lists are a common way of reporting performance in cardiac
      surgery; however, rankings have shown to be imprecise, yet the extent of this
      imprecision is unknown. We aimed to determine the precision of, and fluctuations
      in, ranking lists in the comparison of cardiac surgery mortality rates. METHODS
      AND RESULTS: Information on all adult cardiac surgery patients in all 16
      cardiothoracic centers in The Netherlands from January 1, 2007, until December
      31, 2009, was extracted from the database of the Netherlands Association for
      Cardio-Thoracic Surgery (n=46883). Ranks were assessed using crude and adjusted
      mortality rates, using a random effects logistic regression model. Risk
      adjustment was performed using the logistic EuroSCORE. Statistical precision of
      ranks was assessed with 95% confidence intervals. Additional analyses were
      performed for patients with isolated coronary artery bypass grafting. The ranking
      lists, based on mortality rates in 3 consecutive years, showed considerable
      reshuffling. When all data were pooled, the mean width of the 95% confidence
      intervals was 10 ranks using crude and 8 ranks using adjusted mortality rates.
      The large overlap of the confidence intervals across hospitals indicates that
      rank statistics were not materially different. Results were similar in the
      isolated coronary artery bypass grafting subgroup. CONCLUSIONS: Rankings are an
      imprecise statistical method to report cardiac surgery mortality rates and prone
      to (random) fluctuation. Hence, reshuffling of ranks can be expected solely due
      to chance. Therefore, we strongly discourage the use of ranking lists in the
      comparison of mortality rates.

PMID- 22592753
TI  - Predictors of self-report of heart failure in a population-based survey of older
      adults.
AB  - BACKGROUND: Little research has been conducted on the predictors of self-report
      or patient awareness of heart failure (HF) in a population-based survey. The
      objective of this study was to (1) test the agreement between Medicare
      administrative and Health and Retirement Study (HRS) survey data and (2)
      determine predictors associated with self-report of HF, using a validated
      Medicare claims algorithm as the reference standard. We hypothesized that those
      who self-reported HF were more likely to have a higher number of HF-related
      claims. METHODS AND RESULTS: Secondary data analysis was conducted using the 2004
      wave of the HRS linked to 2002 to 2004 Medicare claims (n=5573 respondents aged
      >= 67 years). Concordance between self-report of HF in the HRS and Medicare
      claims was calculated. Logistic regression was performed to identify predictors
      associated with self-report HF. HF prevalence by self-report was 4.6%. Self
      report of HF and claims agreement was 87% (kappa=0.34). The presence of >1 HF
      inpatient claims was associated with greater odds of self-report (odds ratio
      [OR], 1.92; 95% CI, 1.23-3.00). Greater odds of self-reporting HF was also
      associated with >= 4 HF claims (OR, 2.74; 95% CI, 1.36-5.52). Blacks (OR, 0.28;
      95% CI, 0.14-0.55) and Hispanics (OR, 0.30; 95% CI, 0.11-0.83) were less likely
      to self-report HF compared with whites in the final model. CONCLUSIONS: Self
      report of HF is an insensitive method for accurately identifying HF cases,
      especially in those with less-severe disease and who are nonwhite. There may be
      limited awareness of HF among older minority patients despite having clinical
      encounters during which HF is coded as a diagnosis.

PMID- 22592755
TI  - No "i" in Heart Team: incentivizing multidisciplinary care in cardiovascular
      medicine.

PMID- 22592756
TI  - Percutaneous closure of patent foramen ovale: a near-perfect treatment ruined by
      careful study?

PMID- 22592757
TI  - Most important outcomes research papers in cardiovascular disease in the elderly.
AB  - The following are highlights from the new series, Circulation: Cardiovascular
      Quality and Outcomes Topic Review. This series will summarize the most important
      manuscripts, as selected by the Editor, that have published in the Circulation
      portfolio. The objective of this new series is to provide our readership with a
      timely, comprehensive selection of important papers that are relevant to the
      quality and outcomes and general cardiology audience. The studies included in
      this article represent the most significant research in the area of
      cardiovascular disease in the elderly.

PMID- 22592759
TI  - Melanocortin-4 receptor expression in different classes of spinal and vagal
      primary afferent neurons in the mouse.
AB  - Melanocortin-4 receptor (MC4R) ligands are known to modulate nociception, but the
      site of action of MC4R signaling on nociception remains to be elucidated. The
      current study investigated MC4R expression in dorsal root ganglia (DRG) of the
      MC4R-GFP reporter mouse. Because MC4R is known to be expressed in vagal afferent
      neurons in the nodose ganglion (NG), we also systematically compared MC4R
      expressing vagal and spinal afferent neurons. Abundant green fluorescent protein
      (GFP) immunoreactivity was found in about 45% of DRG neuronal profiles (at the
      mid-thoracic level), the majority being small-sized profiles.
      Immunohistochemistry combined with in situ hybridization confirmed that GFP was
      genuinely produced in MC4R-expressing neurons in the DRG. While a large number of
      GFP profiles in the DRG coexpressed Nav1.8 mRNA (84%) and bound isolectin B4
      (72%), relatively few GFP profiles were positive for NF200 (16%) or CGRP (13%),
      suggesting preferential MC4R expression in C-fiber nonpeptidergic neurons. By
      contrast, GFP in the NG frequently colocalized with Nav1.8 mRNA (64%) and NF200
      (29%), but only to a moderate extent with isolectin B4 (16%). Lastly, very few
      GFP profiles in the NG expressed CGRP (5%) or CART (4%). Together, our findings
      demonstrate variegated MC4R expression in different classes of vagal and spinal
      primary afferent neurons, and underscore the role of the melanocortin system in
      modulating nociceptive and nonnociceptive peripheral sensory modalities.

PMID- 22592761
TI  - Pharmaco-induced erections for penile color-duplex ultrasound: oral PDE5
      inhibitors or intracavernosal injection?
AB  - To prospectively compare the clinical responses and penile color-duplex
      ultrasound (PCDU) results of oral PDE5 inhibitors (PDE5-Is) with papaverine
      intracavernosal injection (ICI) and to evaluate whether PDE5-Is could be used as
      alternatives to vasoactive agent injections, 25 ED patients underwent PCDU three
      times with an interval of at least 1 week, using different pharmacological
      induction: ICI mode (30-60 mg papaverine), sildenafil mode (100 mg sildenafil)
      and tadalafil mode (20 mg tadalafil). The preference of the patients was
      collected when all tests were completed. No significant differences were found in
      peak systolic velocity and acceleration time among all three modes. However for
      the ICI mode, end diastolic velocity of the right cavernosal artery was
      significantly higher than those of the sildenafil and tadalafil modes 5 min after
      erection induction, and at 15 min it became lower than those of two PDE5-I modes.
      Consequently, resistance index of the right cavernosal artery in ICI mode was
      reversed at 5 and 15 min. In all, 60.0 and 56.0% patients managed to reach full
      erection in PDE5-Is modes, which was significantly lower than in ICI mode
      (80.0%). Therefore, although PDE5-Is and papaverine ICI showed similar effects on
      PCDU parameters in detecting arterial ED, more patients had better clinical
      responses to ICI, and oral PDE5-Is administration still showed some pitfalls in
      practical use.

PMID- 22592760
TI  - Vesicouterine fistulae: our experience of 17 cases and literature review.
AB  - AIM: A retrospective study of vesicouterine fistulae managed from 1996 to 2011
      analyzed the incidence, symptomatology, diagnosis, and surgical outcome. PATIENTS
      & METHODS: During the study period, 17 patients were managed, of whom 14
      underwent abdominal repair and three underwent vaginal repair. Mean patient age
      was 31.1 years and mean follow-up 7.3 years. RESULTS: Vesicouterine fistulae
      resulted following cesarean section in 13 patients and vaginal delivery in four.
      Eleven patients presented with urinary leakage via the vagina and seven with
      menouria. All patients had successful outcomes irrespective of treatment
      approach. The uterus was conserved in ten patients, of whom seven had completed
      their childbearing. The remaining three conceived spontaneously and underwent
      elective cesarean section. CONCLUSION: The majority of vesicouterine fistulae
      occur following cesarean section, and it is feasible to achieve 100 % successful
      repair. Though the majority require abdominal repair, a few selected cases can be
      successfully repaired vaginally.

PMID- 22592762
TI  - Characterization of corpus cavernosum smooth muscle cell phenotype in diabetic
      rats with erectile dysfunction.
AB  - Phenotypic modulation from a contractile to a proliferative state within vascular
      smooth muscle cells has a critical role in the pathogenesis of a variety of
      cardiovascular diseases. To investigate the characterization of corpus cavernosum
      smooth muscle cell phenotype in diabetic rats with erectile dysfunction, a group
      of Sprague-Dawley rats (n=30) were induced by intraperitoneal injection of
      streptozotocin (60 mg kg(-1)) and screened by subcutaneous injection of
      apomorphine (100 MUg kg(-1)) for the measurement and comparison of the penile
      erections, and then three different groups were defined. Primary corpus
      cavernosum smooth muscle cells were cultured and passaged. The cavernous tissue
      segments were subjected to quantitative real-time polymerase chain reaction to
      determine the expressions of smooth muscle alpha-actin (SMA), SM myosin heavy
      chain (SMMHC), smoothelin, calponin and myocardin. Cell contractility in vitro
      and western blot analysis of SMA and SMMHC in the cavernous tissues and cells
      were determined. Compared with the control group (n=8) and the diabetes mellitus
      group (n=5), the expressions of SMA, calponin, SMMHC, smoothelin and myocardin
      mRNA were decreased in the cavernous tissues in rats of the diabetic erectile
      dysfunction group (n=15; P=0.001 and 0.02, P=0.014 and 0.012, both P<0.001,
      P=0.005 and <0.001, P=0.003 and 0.035, respectively). The levels of SMA and SMMHC
      proteins showed a significant decrease in cavernous tissues and cultured cells in
      rats of the diabetic erectile dysfunction group. Cells of the diabetic erectile
      dysfunction group exhibited significantly less contractility compared with those
      of other groups (P<0.001). Corpus cavernosum SM cell possesses the ability to
      modulate the phenotype under hyperglycemic conditions, which could have a key
      role in the pathogenesis of diabetic erectile dysfunction.

PMID- 22592763
TI  - Gastroesophageal reflux disease and sleep disturbances.
AB  - Nighttime reflux during sleep plays a crucial role in several conditions
      associated with gastroesophageal reflux disease (GERD). Reflux patterns during
      arousal and sleep are different because of delayed gastric emptying, reduced
      esophageal peristalsis, decreases in swallowing and salivary secretion, and
      prolonged esophageal clearance during sleep. Clinical evidence strongly suggests
      that GERD is associated with sleep disturbances such as shorter sleep duration,
      difficulty falling asleep, arousals during sleep, poor sleep quality, and
      awakening early in the morning. New mechanisms on how GERD affects sleep have
      been recently identified by using actigraphy, and sleep deprivation was found to
      induce esophageal hyperalgesia to acid perfusion. Thus, the relationship between
      GERD and sleep disturbances is bidirectional. Among lifestyle modifications,
      avoidance of a late night meal plays a role in prevention of nighttime reflux.
      Treatment with a proton pump inhibitor (PPI) improves both nighttime symptoms and
      subjective sleep parameters, but its effects on objective sleep parameters remain
      unclear. Better control of nighttime acid secretion by administering a PPI at
      different times or by providing a double-dose PPI, adding H(2) receptor
      antagonists, or other new agents is proposed. The effects of such treatments on
      sleep disturbances remain to be elucidated. GERD patients with sleep disturbances
      report more severe symptoms and poorer quality of life as compared to those
      without sleep disturbances. Consequently, GERD should also be classified as GERD
      with sleep disturbance and GERD without sleep disturbance.

PMID- 22592771
TI  - The 6th Russian School of Colorectal Surgery meeting : 5-6 April 2012, Moscow,
      Russia.

PMID- 22592770
TI  - Characterization of nitric oxide signaling pathways in the mouse retina.
AB  - Nitric oxide (NO) is a gaseous neuromodulator with physiological functions in
      every retinal cell type. NO is synthesized by several nitric oxide synthases
      (NOS) and often functions through its second messenger, cyclic guanosine
      monophosphate (cGMP), and protein kinase G (PKG). This study combined NO imaging,
      immunocytochemistry, biochemistry, and molecular biology to localize NO and its
      downstream signaling pathways in the mouse retina. Neuronal NOS (nNOS) was
      localized primarily in puncta in the inner plexiform layer, in amacrine cells,
      and in somata in the ganglion cell layer. Endothelial NOS was in blood vessels.
      Light-stimulated NO production imaged with diaminofluorescein was present in
      somata in the inner nuclear layer and in synaptic boutons in the inner plexiform
      layer. The downstream target of NO, soluble guanylate cyclase (sGC), was in
      somata in the inner and outer nuclear layers and in both plexiform layers. Cyclic
      GMP immunocytochemistry was used functionally to localize sGC that was activated
      by an NO donor in amacrine, bipolar, and ganglion cells. Cyclic GMP-dependent
      protein kinase (PKG) Ialpha was found in bipolar cells, ganglion cells, and both
      plexiform layers, whereas PKG II was found in the outer plexiform layer, amacrine
      cells, and somata in the ganglion cell layer. This study shows that the
      NO/cGMP/PKG signaling pathway is functional and widely distributed in specific
      cell types in the outer and inner mouse retina. A better understanding of these
      signaling pathways in normal retina will provide a firm basis for targeting their
      roles in retinal pathology.

PMID- 22592772
TI  - Attenuation of monocrotaline-induced pulmonary arterial hypertension in rats by
      rosuvastatin.
AB  - BACKGROUND: Although the effects of statins on pulmonary arterial hypertension
      (PAH) have been studied previously, the results remain uncertain. OBJECTIVE: The
      aim of this study was to confirm the impacts of rosuvastatin on monocrotaline
      (MCT)-induced PAH and potential mechanisms. METHODS: Rats were subjected to a
      single subcutaneous injection of MCT to induce PAH. In the prevention protocol,
      the rats received different doses of rosuvastatin (2 and 10 mg.kg.d) for 4 weeks
      since MCT injection, whereas in the treatment protocol, the rats received
      different doses of rosuvastatin 4 weeks after MCT injection for 4 weeks. At the
      end of the studies, hemodynamic parameters were measured, and the morphology of
      small pulmonary arteries (SPAs) and right ventricular hypertrophy were assessed.
      The expression of proliferating cell nuclear antigen (PCNA) and endothelial
      nitric oxide synthase (eNOS) in SPAs, and Rho kinase 1 (ROCK-1) and eNOS in lung
      tissue were determined. RESULTS: Rosuvastatin administration could significantly
      lower mean pulmonary arterial pressure in both prevention and treatment protocols
      (P < 0.01, respectively), improve survival after PAH development (P < 0.05), and
      reduce wall thickening of SPAs and right ventricular hypertrophy (P < 0.01,
      respectively). At the molecular level, rosuvastatin could inhibit the expression
      of ROCK-1 (P < 0.05, respectively) and PCNA (P < 0.01, respectively) but restore
      the expression of eNOS (P < 0.05, respectively). These effects were found in a
      dose-dependent manner. CONCLUSIONS: The present data confirmed and extended the
      previous data regarding the protective impacts of statins on PAH. The effects of
      rosuvastatin seemed to be associated with the regulation of ROCK-1, PCNA, and
      eNOS expression.

PMID- 22592773
TI  - Reassessment of a suggested pharmacological approach to heart failure: L-arginine
      is only a marginal NO donor in pigs.
AB  - OBJECTIVES: L-Arginine has been tested in various cardiovascular diseases, mainly
      to improve endothelial function through NO production. However, as the results
      have been partly unpredictable, we assessed the hemodynamic, energetic and
      metabolic effects of L-arginine to clarify any potential benefits in postischemic
      left ventricular (LV) dysfunction. METHODS: LV dysfunction was induced by
      repetitive brief coronary occlusions in 12 anesthetized, open chest pigs. L
      Arginine was subsequently infused (bolus 400 mg.kg and continuously for 1 hour,
      250 mg.kg.h). Hemodynamic parameters, metabolites of L-arginine and myocardial
      energetics were assessed sequentially. RESULTS: L-Arginine infusions caused a
      substantial rise in plasma L-arginine (3474 +/- 358 MUmole.L) accompanied by a 2
      fold increase in plasma L-citrulline. No significant alterations in vascular
      resistance or LV contractility were observed from L-arginine. Mean arterial
      pressure dropped from 78 +/- 11 to 72 +/- 10 mm Hg (P = 0.019) and 70 +/- 8 mm Hg
      (P = 0.003) after bolus and infusions, respectively. Myocardial oxygen
      consumption was unaltered, and myocardial creatine content was not increased
      after 90 minutes of L-arginine infusion. CONCLUSION: L-Arginine infusion did not
      influence the energetic cost of myocardial contractility, and only minor
      hemodynamic changes were observed despite a demonstrable turnover of L-arginine.
      These findings question the use of L-arginine to promote therapeutic NO formation
      in the acute setting.

PMID- 22592774
TI  - Role of delta2 opioid receptor in cardioprotection against hypoxia-reoxygenation
      injury.
AB  - Several lines of in vivo evidence demonstrated that activation of delta-opioid
      receptors (ORs) with agonists mimics the cardioprotective effect of ischemic
      preconditioning. However, the subtypes of ORs involved and the molecular and
      cellular mechanisms are not entirely clear. To investigate the significance of
      the contribution by delta ORs to cardiomyocyte survival, we used an in vitro
      model of hypoxia/reoxygenation (H/R) in primary cultures of neonatal rat
      cardiomyocytes to study the role of different delta ORs in cardiomyocyte
      apoptosis and the relevant downstream signaling pathway. The results showed that
      apoptosis in neonatal cardiomyocytes induced by H/R was reversed by delta2 OR
      agonist, deltorphin E but not by delta1 OR agonist DPDPE; the deltorphin E
      induced cytoprotection was totally abrogated by the MEK inhibitor PD98059 and
      overexpression of dominant interfering form of MEK1; in contrast, overexpression
      of constitutive active form of MEK1 exerted a similar protective effect as
      deltorphin E. These results suggest that delta2 OR, but not delta1 OR, plays a
      key role in preventing cardiomyocytes from apoptosis during H/R injury, which is
      mainly mediated by the MEK/ERK1/2 pathway.

PMID- 22592775
TI  - MYMIV-AC2, a geminiviral RNAi suppressor protein, has potential to increase the
      transgene expression.
AB  - Gene silencing is one of the limiting factors for transgene expression in plants.
      But the plant viruses have learnt to suppress gene silencing by encoding the
      protein(s), called RNA silencing suppressor(s) (RSS). Hence, these proteins could
      be used to overcome the limitation for transgene expression. The RNAi
      suppressors, namely HC-Pro and P19, have been shown to enhance the transgene
      expression but other RSS proteins have not been screened for similar role.
      Moreover, none of RSSs from the DNA viruses are known for enhancing the
      expression of transgenes. The Mungbean Yellow Mosaic India Virus (MYMIV)
      belonging to the genus Begomovirus within the family of Geminiviridae encodes an
      RSS called the AC2 protein. Here, we used AC2 to elevate the expression of the
      transgenes. Upon introduction of MYMIV-AC2 in the silenced GFP transgenic tobacco
      lines, by either genetic hybridisation or transgenesis, the GFP expression was
      enhanced several fold in F1 and T0 lines. The GFP-siRNA levels were much reduced
      in F1 and T0 lines compared with those of the initial parental silenced lines.
      The enhanced GFP expression was also observed at the cellular level. This
      approach was also successful in enhancing the expression of another transgene,
      namely topoisomeraseII.

PMID- 22592776
TI  - Improvement of hydrogen productivity by introduction of NADH regeneration pathway
      in Clostridium paraputrificum.
AB  - To improve the hydrogen productivity and examine the hydrogen evolution mechanism
      of Clostridium paraputrificum, roles of formate in hydrogen evolution and effects
      of introducing formate-originated NADH regeneration were explored. The formate
      decomposing pathway for hydrogen production was verified to exist in C.
      paraputrificum. Then NAD(+)-dependent formate dehydrogenase FDH1 gene (fdh1) from
      Candida boidinii was overexpressed, which regenerate more NADH from formate to
      form hydrogen by NADH-mediated pathway. With fdh1 overexpression, the hydrogen
      yield via NADH-involving pathway increased by at least 59 % compared with the
      control. Accompanied by the change of hydrogen metabolism, the whole cellular
      metabolism was redistributed greatly.

PMID- 22592777
TI  - Biosynthesis of silver nanoparticles using latex from few Euphorbian plants and
      their antimicrobial potential.
AB  - The synthesis of well-dispersed and ultrafine metal nanoparticles has great
      interest due to their distinctive physicochemical properties and biomedical
      applications. This study is the first report of one-step solvent-free synthesis
      of AgNPs using Euphorbiaceae plant latex. Among evaluated eight latex-producing
      plants, four (Jatropha curcas, Jatropha gossypifolia, Pedilanthus tithymaloides,
      and Euphorbia milii) showed high potential to produce physicochemically distinct,
      small-sized and bactericidal AgNPs. Phytochemical screening showed presence of
      rich amount of biochemicals in these plants. J. gossypifolia showed uniformly
      dispersed comparatively small-sized AgNPs. Dose-dependent growth inhibition of
      bacterial pathogens Escherichia coli, Pseudomonas aeruginosa, Staphylococcus
      aureus, Staphylococcus epidermis, and Micrococcus luteus was observed for J.
      gossypifolia latex-synthesized AgNPs with minimum inhibitory concentration values
      30, 40, 70, 60, and 60 ppm, respectively, after 24 h. Possible mode of action of
      AgNPs against pathogens was confirmed by analyzing enzymes and cell leakage.

PMID- 22592778
TI  - Investigation of factors affecting controlled release from photosensitive DMPC
      and DSPC liposomes.
AB  - An investigation of liposomes comprised of 1,2-dimyristoyl-sn-glycero-3
      phosphocholine (DMPC) or 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) lipids
      with cholesterol and zinc phthalocyanine (ZnPC) revealed that several fundamental
      liposome properties are influenced by composition and by lipid-specific features.
      DMPC and DSPC liposomes were synthesized, and their compositional changes,
      encapsulation capacities, morphologies, and release properties were evaluated. In
      this research, liposome degradation, lysis, and content release were initiated by
      photolysis, i.e., rupture induced by exposure to light. A controlled release
      mechanism was created through the introduction of photosensitizers (i.e., ZnPC)
      embedded within the cholesterol-stabilized liposome membrane. The light
      wavelength and light exposure time accelerated photodegradation properties of
      DMPC liposomes compared to DSPC liposomes, which exhibited a slower release rate.
      Morphological changes in the liposomes were strongly influenced by light
      wavelength and light exposure time. For both the DMPC and DSPC liposomes, visible
      light with wavelengths in the red end of the spectrum and broad spectrum ambient
      lighting (400-700 nm) were more effective for lysis than UV-A light (365 nm).
      Heating liposomes to 100  degrees C decreased the stability of liposomes compared
      to liposomes kept at room temperatures. In addition, the optimal lipid-to
      cholesterol-to-photoactivator ratio that produced the most stable liposomes was
      determined.

PMID- 22592780
TI  - Heavy metal contamination of urban soils and dusts in Guangzhou, South China.
AB  - The heavy metal concentrations of soil and dust samples from roadside,
      residential areas, parks, campus sport grounds, and commercial sites were studied
      in Guangzhou, South China. Heavy metals in samples were determined by inductively
      coupled plasma atomic emission spectrophotometer following acidic digestion with
      HClO(4) + HF + HNO(3). High concentrations, especially of Cd, Pb, and Zn, were
      found with mean concentrations of Cd, Cr, Cu, Ni, Pb, and Zn in the urban dusts
      being 4.22 +/- 1.21, 62.2 +/- 27.1, 116 +/- 30, 31.9 +/- 12.6, 72.6 +/- 17.9, and
      504 +/- 191 mg/kg dry weight, respectively. The respective levels in urban soils
      (0.23 +/- 0.19, 22.4 +/- 13.8, 41.6 +/- 29.4, 11.1 +/- 5.3, 65.4 +/- 40.2, and
      277 +/- 214 mg/kg dry weight, respectively), were significantly lower. The
      integrated pollution index of six metals varied from 0.25 to 3.4 and from 2.5 to
      8.4 in urban soils and dusts, respectively, with 61 % of urban soil samples being
      classified as moderately to highly polluted and all dust samples being classified
      as highly polluted. The statistical analysis results for the urban dust showed
      good agreement between principal component analysis and cluster analysis, but
      distinctly different elemental associations and clustering patterns were observed
      among heavy metals in the urban soils. The results of multivariate statistic
      analysis indicated that Cr and Ni concentrations were mainly of natural origin,
      while Cd, Cu, Pb, and Zn were derived from anthropogenic activities.

PMID- 22592781
TI  - Rate of occurrence of failures based on a nonhomogeneous Poisson process: an
      ozone analyzer case study.
AB  - Atmospheric pollutant monitoring constitutes a primordial activity in public
      policies concerning air quality. In Sao Paulo State, Brazil, the Sao Paulo State
      Environment Company (CETESB) maintains an automatic network which continuously
      monitors CO, SO(2), NO(x), O(3), and particulate matter concentrations in the
      air. The monitoring process accuracy is a fundamental condition for the actions
      to be taken by CETESB. As one of the support systems, a preventive maintenance
      program for the different analyzers used is part of the data quality strategy.
      Knowledge of the behavior of analyzer failure times could help optimize the
      program. To achieve this goal, the failure times of an ozone analyzer-considered
      a repairable system-were modeled by means of the nonhomogeneous Poisson process.
      The rate of occurrence of failures (ROCOF) was estimated for the intervals 0
      70,800 h and 0-88,320 h, in which six and seven failures were observed,
      respectively. The results showed that the ROCOF estimate is influenced by the
      choice of the observation period, t(0) = 70,800 h and t(7) = 88,320 h in the
      cases analyzed. Identification of preventive maintenance actions, mainly when
      parts replacement occurs in the last interval of observation, is highlighted,
      justifying the alteration in the behavior of the inter-arrival times. The
      performance of a follow-up on each analyzer is recommended in order to record the
      impact of the performed preventive maintenance program on the enhancement of its
      useful life.

PMID- 22592779
TI  - Cloning, functional characterization and genomic organization of 1,8-cineole
      synthases from Lavandula.
AB  - Several members of the genus Lavandula produce valuable essential oils (EOs) that
      are primarily constituted of the low molecular weight isoprenoids, particularly
      monoterpenes. We isolated over 8,000 ESTs from the glandular trichomes of L. x
      intermedia flowers (where bulk of the EO is synthesized) to facilitate the
      discovery of genes that control the biosynthesis of EO constituents. The
      expression profile of these ESTs in L. x intermedia and its parents L.
      angustifolia and L. latifolia was established using microarrays. The resulting
      data highlighted a differentially expressed, previously uncharacterized cDNA with
      strong homology to known 1,8-cineole synthase (CINS) genes. The ORF, excluding
      the transit peptide, of this cDNA was expressed in E. coli, purified by Ni-NTA
      agarose affinity chromatography and functionally characterized in vitro. The ca.
      63 kDa bacterially produced recombinant protein, designated L. x intermedia CINS
      (LiCINS), converted geranyl diphosphate (the linear monoterpene precursor)
      primarily to 1,8-cineole with K ( m ) and k ( cat ) values of 5.75 MUM and 8.8 *
      10(-3) s(-1), respectively. The genomic DNA of CINS in the studied Lavandula
      species had identical exon-intron architecture and coding sequences, except for a
      single polymorphic nucleotide in the L. angustifolia ortholog which did not alter
      protein function. Additional nucleotide variations restricted to L. angustifolia
      introns were also observed, suggesting that LiCINS was most likely inherited from
      L. latifolia. The LiCINS mRNA levels paralleled the 1,8-cineole content in mature
      flowers of the three lavender species, and in developmental stages of L. x
      intermedia inflorescence indicating that the production of 1,8 cineole in
      Lavandula is most likely controlled through transcriptional regulation of LiCINS.

PMID- 22592782
TI  - Speciation and antimicrobial resistance of Enterococci isolated from recreational
      beaches in Malaysia.
AB  - We report the first study on the occurrence of antibiotic-resistant enterococci
      in coastal bathing waters in Malaysia. One hundred and sixty-five enterococci
      isolates recovered from two popular recreational beaches in Malaysia were
      speciated and screened for antibiotic resistance to a total of eight antibiotics.
      Prevalence of Enterococcus faecalis and Enterococcus faecium was highest in both
      beaches. E. faecalis/E. faecium ratio was 0.384:1 and 0.375:1, respectively, for
      isolates from Port Dickson (PD) and Bagan Lalang (BL). Analysis of Fisher's exact
      test showed that association of prevalence of E. faecalis and E. faecium with
      considered locations was not statistically significant (p < 0.05). Chi-square
      test revealed significant differences (chi(2) = 82.630, df = 20, p < 0.001) in
      the frequency of occurrence of enterococci isolates from the considered sites.
      Resistance was highest to nalidixic acid (94.84 %) and least for chloramphenicol
      (8.38 %). One-way ANOVA using Tukey-Kramer multiple comparison test showed that
      resistance to ampicillin was higher in PD beach isolates than BL isolates and the
      difference was extremely statistically significant (p < 0.0001). Frequency of
      occurrence of multiple antibiotic resistance (MAR) isolates were higher for PD
      beach water (64.29 %) as compared to BL beach water (13.51 %), while MAR indices
      ranged between 0.198 and 0.48. The results suggest that samples from Port Dickson
      may contain MAR bacteria and that this could be due to high-risk faecal
      contamination from sewage discharge pipes that drain into the sea water.

PMID- 22592783
TI  - Approaches to systematic assessment of environmental exposures posed at hazardous
      waste sites in the developing world: the Toxic Sites Identification Program.
AB  - In the developing world, environmental chemical exposures due to hazardous waste
      sites are poorly documented. We describe the approach taken by the Blacksmith
      Institute's Toxic Sites Identification Program in documenting environmental
      chemical exposures due to hazardous waste sites globally, identifying sites of
      concern and quantifying pathways, populations, and severity of exposure. A
      network of local environmental investigators was identified and trained to
      conduct hazardous waste site investigations and assessments. To date, 2,095
      contaminated sites have been identified within 47 countries having an estimated
      population at risk of 71,500,000. Trained researchers and investigators have
      visited 1,400 of those sites. Heavy metals are the leading primary exposures,
      with water supply and ambient air being the primary routes of exposure. Even
      though chemical production has occurred largely in the developed world to date,
      many hazardous waste sites in the developing world pose significant hazards to
      the health of large portions of the population. Further research is needed to
      quantify potential health and economic consequences and identify cost-effective
      approaches to remediation.

PMID- 22592784
TI  - Forest biomonitoring of the largest Slovene thermal power plant with respect to
      reduction of air pollution.
AB  - The condition of the forest ecosystem in the vicinity of the largest Slovene
      power plant [the Sostanj Thermal Power Plant (STPP)] was monitored during the
      period 1991-2008 by determining the total concentration of sulphur, ascorbic acid
      and chlorophyll in Norway spruce needles. After 1995, the introduction of
      cleaning devices at the STPP dramatically reduced the former extremely high SO(2)
      and dust emissions. The most significant findings of this comprehensive, long
      duration survey are as follows: (1) the chosen parameters are suitable
      bioindicators of stress caused by air pollution in Norway spruce needles; they
      reflect both spatial and temporal variations in air pollution as well as the
      degree of efficiency of the cleaning devices; (2) observations show that the
      physiological condition of Norway spruce in northern Slovenia has significantly
      improved since 1995, when the first desulphurization device at STPP was built,
      together with a reduction in the area influenced by pollution from STPP; (3)
      metabolic processes in spruce needles react to air pollution according to the
      severity of the pollution and the length of exposure; exposure to high SO(2)
      ambient levels and/or spread over a long duration can damage the antioxidant
      defence mechanisms of spruce trees as well as diminishing the concentration of
      ascorbic acid; (4) a reduction in the exposure to air pollution improves the
      vitality of the trees (e.g. higher concentrations of total (a + b) chlorophyll),
      as well as restoring their defence capabilities as shown by higher concentrations
      of ascorbic acid; and (5) forest monitoring should be continued and focused on
      integrating the effects of multiple stressors, which can additionally affect a
      forest ecosystem.

PMID- 22592785
TI  - Heavy metal risk assessment for potatoes grown in overused phosphate-fertilized
      soils.
AB  - The long-term application of phosphate fertilizers on vegetable production fields
      has raised concerns about the potential health risks of heavy metal contamination
      of crops grown on contaminated soils in the Hamadan province, western Iran. This
      study found that long-term fertilizer use led to a growing accumulation of heavy
      metals in soils. High concentrations of elemental As, Cd, Cr, Cu, Pb, and Zn were
      found in potatoes sampled from overused phosphate-fertilized soils, which
      increased the daily intake of metals in food. However, the ingestion of potatoes
      from soils affected by phosphate fertilizers posed a low health risk when
      compared with the health risk index of <1 for heavy metals. Nevertheless, heavy
      metal concentrations should be periodically monitored in vegetables grown in
      these soils. It would also be beneficial to implement effective remediation
      technologies to minimize possible impacts on human health.

PMID- 22592786
TI  - Partition of heavy metals in a tropical river system impacted by municipal waste.
AB  - A research program was established to identify the governing factors for the
      partition coefficient (K(D)) of heavy metals between suspended particulate and
      dissolved phases in the Day River system a tropical, highly alluvial aquatic
      system, in Vietnam. The targeted river system, draining an urbanized
      industrialized catchment where discharged wastewater is mostly untreated, could
      be separated into the least impacted, pristine area, and the most impacted,
      polluted area. Organic matter degradation was shown to govern the variation of
      parameters like total organic carbon, biochemical oxygen demand, chemical oxygen
      demand, nutrients, conductivity, or redox potential. Heavy metals in both
      dissolved and particulate phases were enriched in severely polluted area because
      of wastewater inflow that contains concentrated metals and intensification of
      metal influx from sediment. Results show log K(D) in the order Mn < As < Zn < Hg
      < Ni < Cu < Cd < Co < Pb < Cr < Fe and As < Zn < Ni < Mn < Cr < Cu < Co < Fe in
      the polluted zone and the pristine zone, respectively. A decreasing tendency of
      partition coefficients of 11 heavy metals considered from the pristine to the
      impacted zones was observed. Three explanations for the difference are: (1)
      increase of solubility of most heavy metals in low redox potential, (2)
      competition for the binding sites with major and minor cations, and (3)
      complexation with dissolved organic matter concentrated in municipal waste
      impacted water. Apart from domestic waste impact, statistical analysis has
      contributed to identify the influence of climate condition and hydrological
      regime to the partition of heavy metals in the area.

PMID- 22592787
TI  - Fibroblast growth factor 2 regulates adequate nigrostriatal pathway formation in
      mice.
AB  - Fibroblast growth factor 2 (FGF-2) is an important neurotrophic factor that
      promotes survival of adult mesencephalic dopaminergic (mDA) neurons and regulates
      their adequate development. Since mDA neurons degenerate in Parkinson's disease,
      a comprehensive understanding of their development and maintenance might
      contribute to the development of causative therapeutic approaches. The current
      analysis addressed the role of FGF-2 in mDA axonal outgrowth, pathway formation,
      and innervation of respective forebrain targets using organotypic explant
      cocultures of ventral midbrain (VM) and forebrain (FB). An enhanced green
      fluorescent protein (EGFP) transgenic mouse strain was used for the VM explants,
      which allowed combining and distinguishing of individual VM and FB tissue from
      wildtype and FGF-2-deficient embryonic day (E)14.5 embryos, respectively. These
      cocultures provided a suitable model to study the role of target-derived FB and
      intrinsic VM-derived FGF-2. In fact, we show that loss of FGF-2 in both FB and VM
      results in significantly increased mDA fiber outgrowth compared to wildtype
      cocultures, proving a regulatory role of FGF-2 during nigrostriatal wiring.
      Further, we found in heterogeneous cocultures deficient for FGF-2 in FB and VM,
      respectively, similar phenotypes with wider fiber tracts compared to wildtype
      cocultures and shorter fiber outgrowth distance than cocultures completely
      deficient for FGF-2. Additionally, the loss of target-derived FGF-2 in FB
      explants resulted in decreased caudorostral glial migration. Together these
      findings imply an intricate interplay of target-derived and VM-derived FGF
      signaling, which assures an adequate nigrostriatal pathway formation and target
      innervation.

PMID- 22592788
TI  - Crust-mantle mechanical coupling in Eastern Mediterranean and eastern Turkey.
AB  - Present-day crust-mantle coupling in the Eastern Mediterranean and eastern Turkey
      is studied using the Global Positioning System (GPS) and seismic anisotropy data.
      The general trend of the shear wave fast-splitting directions in NE Turkey and
      Lesser Caucaus align well with the geodetic velocities in an absolute plate
      motion frame of reference pointing to an effective coupling in this part of the
      region of weak surface deformation. Farther south, underneath the Bitlis Suture,
      however, there are significant Pn delays with E-W anisotropy axes indicating
      significant lateral escape. Meanwhile, the GPS reveals very little surface
      deformation. This mismatch possibly suggests a decoupling along the suture. In
      the Aegean, the shear wave anisotropy and the Pn anisotropy directions agree with
      the extensional component of the right-lateral shear strains except under the
      Crete Basin and other parts of the southern Aegean Sea. This extensional
      direction matches perfectly also with the southward pulling force vectors across
      the Hellenic trench; however, the maximum right-lateral shear directions obtained
      from the GPS data in the Aegean do not match either of these anisotropies.
      Seismic anisotropy from Rayleigh waves sampled at 15 s, corresponding to the
      lower crust, match the maximum right-lateral maximum shear directions from the
      GPS indicating decoupling between the crust and the mantle. This decoupling most
      likely results from the lateral variations of the gravitational potential
      energies and the slab-pull forces.

PMID- 22592792
TI  - Mice take calculated risks.
AB  - Animals successfully navigate the world despite having only incomplete
      information about behaviorally important contingencies. It is an open question to
      what degree this behavior is driven by estimates of stochastic parameters (brain
      constructed models of the experienced world) and to what degree it is directed by
      reinforcement-driven processes that optimize behavior in the limit without
      estimating stochastic parameters (model-free adaptation processes, such as
      associative learning). We find that mice adjust their behavior in response to a
      change in probability more quickly and abruptly than can be explained by
      differential reinforcement. Our results imply that mice represent probabilities
      and perform calculations over them to optimize their behavior, even when the
      optimization produces negligible material gain.

PMID- 22592791
TI  - INVOLVED IN DE NOVO 2-containing complex involved in RNA-directed DNA methylation
      in Arabidopsis.
AB  - At least three pathways control maintenance of DNA cytosine methylation in
      Arabidopsis thaliana. However, the RNA-directed DNA methylation (RdDM) pathway is
      solely responsible for establishment of this silencing mark. We previously
      described INVOLVED IN DE NOVO 2 (IDN2) as being an RNA-binding RdDM component
      that is required for DNA methylation establishment. In this study, we describe
      the discovery of two partially redundant proteins that are paralogous to IDN2 and
      that form a stable complex with IDN2 in vivo. Null mutations in both genes,
      termed IDN2-LIKE 1 and IDN2-LIKE 2 (IDNL1 and IDNL2), result in a phenotype that
      mirrors, but does not further enhance, the idn2 mutant phenotype. Genetic
      analysis suggests that this complex acts in a step in the downstream portion of
      the RdDM pathway. We also have performed structural analysis showing that the
      IDN2 XS domain adopts an RNA recognition motif (RRM) fold. Finally, genome-wide
      DNA methylation and expression analysis confirms the placement of the IDN
      proteins in an RdDM pathway that affects DNA methylation and transcriptional
      control at many sites in the genome. Results from this study identify and
      describe two unique components of the RdDM machinery, adding to our understanding
      of DNA methylation control in the Arabidopsis genome.

PMID- 22592793
TI  - Multiscale diffusion in the mitotic Drosophila melanogaster syncytial blastoderm.
AB  - Despite the fundamental importance of diffusion for embryonic morphogen gradient
      formation in the early Drosophila melanogaster embryo, there remains controversy
      regarding both the extent and the rate of diffusion of well-characterized
      morphogens. Furthermore, the recent observation of diffusional
      "compartmentalization" has suggested that diffusion may in fact be nonideal and
      mediated by an as-yet-unidentified mechanism. Here, we characterize the effects
      of the geometry of the early syncytial Drosophila embryo on the effective
      diffusivity of cytoplasmic proteins. Our results demonstrate that the presence of
      transient mitotic membrane furrows results in a multiscale diffusion effect that
      has a significant impact on effective diffusion rates across the embryo. Using a
      combination of live-cell experiments and computational modeling, we characterize
      these effects and relate effective bulk diffusion rates to instantaneous
      diffusion coefficients throughout the syncytial blastoderm nuclear cycle phase of
      the early embryo. This multiscale effect may be related to the effect of
      interphase nuclei on effective diffusion, and thus we propose that an as-yet
      unidentified role of syncytial membrane furrows is to temporally regulate bulk
      embryonic diffusion rates to balance the multiscale effect of interphase nuclei,
      which ultimately stabilizes the shapes of various morphogen gradients.

PMID- 22592794
TI  - Homeoprotein hhex-induced conversion of intestinal to ventral pancreatic
      precursors results in the formation of giant pancreata in Xenopus embryos.
AB  - Liver and ventral pancreas develop from neighboring territories within the
      endoderm of gastrulae. ventral pancreatic precursor 1 (vpp1) is a marker gene
      that is differentially expressed in a cell population within the dorsal endoderm
      in a pattern partially overlapping with that of hematopoietically expressed
      homeobox (hhex) during gastrulation. In tail bud embryos, vpp1 expression
      specifically demarcates two ventral pancreatic buds, whereas hhex expression is
      mainly restricted to the liver diverticulum. Ectopic expression of a critical
      dose of hhex led to a greatly enlarged vpp1-positive domain and, subsequently, to
      the formation of giant ventral pancreata, putatively by conversion of intestinal
      to ventral pancreatic precursor cells. Conversely, antisense morpholino
      oligonucleotide-mediated knockdown of hhex resulted in a down-regulation of vpp1
      expression and a specific loss of the ventral pancreas. Furthermore, titration of
      hhex with a dexamethasone-inducible hhex-VP16GR fusion construct suggested that
      endogenous hhex activity during gastrulation is essential for the formation of
      ventral pancreatic progenitor cells. These observations suggest that, beyond its
      role in liver development, hhex controls specification of a vpp1-positive
      endodermal cell population during gastrulation that is required for the formation
      of the ventral pancreas.

PMID- 22592795
TI  - Sexual selection and the differential effect of polyandry.
AB  - In principle, widespread polyandry (female promiscuity) creates potential for
      sexual selection in males both before and after copulation. However, the way
      polyandry affects pre- and postcopulatory episodes of sexual selection remains
      little understood. Resolving this fundamental question has been difficult because
      it requires extensive information on mating behavior as well as paternity for the
      whole male population. Here we show that in replicate seminatural groups of red
      junglefowl, Gallus gallus, polyandry eroded variance in male mating success,
      which simultaneously weakened the overall intensity of sexual selection but
      increased the relative strength of postcopulatory episodes. We further illustrate
      the differential effect of polyandry on pre- and postcopulatory sexual selection
      by considering the case of male social status, a key determinant of male
      reproductive success in this species. In low-polyandry groups, however, status
      was strongly sexually selected before copulation because dominants mated with
      more females. In high-polyandry groups, sexual selection for status was weakened
      and largely restricted after copulation because dominants defended paternity by
      mating repeatedly with the same female. These results reveal polyandry as a
      potent and dynamic modulator of sexual selection episodes.

PMID- 22592798
TI  - Canonical autophagy dependent on the class III phosphoinositide-3 kinase Vps34 is
      required for naive T-cell homeostasis.
AB  - The homeostasis of naive T cells is essential for protective immunity against
      infection, but the cell-intrinsic molecular mechanisms that control naive T-cell
      homeostasis are poorly understood. Genetic ablation in lower organisms has
      revealed a critical role for Vps34, an evolutionary conserved class III
      phosphoinositide-3 kinase (PI3K), in regulating endocytosis and autophagy;
      however, the physiological function of Vps34 in the immune system, especially in
      T cells, is unclear. Here we report that Vps34 is required for the maintenance of
      naive T cells, acting in a cell-intrinsic manner. T-cell-specific deletion of the
      gene encoding Vps34 resulted in reduced stability of Vps15 and Beclin-1,
      components of the class III PI3K complex, and impaired autophagy in T cells.
      Vps34 was dispensable for T-cell development but important for the survival of
      naive T cells. Vps34-deficient T cells showed increased mitochondrial mass and
      accumulation of reactive oxygen species, consistent with deficient removal of
      damaged mitochondria. Thus, Vps34-dependent canonical autophagy plays a critical
      role in maintaining T-cell homeostasis by promoting T-cell survival through
      quality control of mitochondria.

PMID- 22592800
TI  - Critical role of soluble amyloid-beta for early hippocampal hyperactivity in a
      mouse model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized by a progressive dysfunction of central
      neurons. Recent experimental evidence indicates that in the cortex, in addition
      to the silencing of a fraction of neurons, other neurons are hyperactive in
      amyloid-beta (Abeta) plaque-enriched regions. However, it has remained unknown
      what comes first, neuronal silencing or hyperactivity, and what mechanisms might
      underlie the primary neuronal dysfunction. Here we examine the activity patterns
      of hippocampal CA1 neurons in a mouse model of AD in vivo using two-photon Ca(2+)
      imaging. We found that neuronal activity in the plaque-bearing CA1 region of
      older mice is profoundly altered. There was a marked increase in the fractions of
      both silent and hyperactive neurons, as previously also found in the cortex.
      Remarkably, in the hippocampus of young mice, we observed a selective increase in
      hyperactive neurons already before the formation of plaques, suggesting that
      soluble species of Abeta may underlie this impairment. Indeed, we found that
      acute treatment with the gamma-secretase inhibitor LY-411575 reduces soluble
      Abeta levels and rescues the neuronal dysfunction. Furthermore, we demonstrate
      that direct application of soluble Abeta can induce neuronal hyperactivity in
      wild-type mice. Thus, our study identifies hippocampal hyperactivity as a very
      early functional impairment in AD transgenic mice and provides direct evidence
      that soluble Abeta is crucial for hippocampal hyperactivity.

PMID- 22592801
TI  - Tumor suppressor p53 (TP53) at the crossroads of the exposome and the cancer
      genome.

PMID- 22592802
TI  - Development of experimental autoimmune encephalomyelitis (EAE) in mice requires
      vitamin D and the vitamin D receptor.
AB  - The development of experimental autoimmune encephalomyelitis (EAE), a model of
      multiple sclerosis, has been studied in mice that were (i) vitamin D-deficient,
      (ii) minus the vitamin D receptor, (iii) minus a vitamin D 25-hydroxylase, and
      (iv) minus the vitamin D 25-hydroxyvitamin D-1alpha-hydroxylase. EAE development
      was markedly suppressed in mice lacking the vitamin D receptor and partially
      suppressed in vitamin D-insufficient mice. However, the absence of either of the
      two key hydroxylases (i.e., 25-hydroxylase and 1alpha-hydroxylase) neither
      inhibits nor enhances the development of EAE. These results indicate that vitamin
      D and the vitamin D receptor are required for the development of EAE. The results
      also suggest that 1,25-dihydroxyvitamin D(3) may not play a role in this
      autoimmune response.

PMID- 22592803
TI  - Monitoring of the prostate tumour cells redox state and real-time proliferation
      by novel biophysical techniques and fluorescent staining.
AB  - The present paper is focused on zinc(ii) treatment effects on prostatic cell
      lines PC-3 (tumour) and PNT1A (non-tumour). Oxidative status of cells was
      monitored by evaluation of expression of metallothionein (MT) isoforms 1A and 2A
      at the mRNA and protein level, glutathione (oxidised and reduced), and
      intracellular zinc(ii) after exposition to zinc(ii) treatment at concentrations
      of 0-150 MUM using electrochemical methods, western blotting and fluorescent
      microscopy. A novel real-time impedance-based growth monitoring system was
      compared with widely used end-point MTT assay. Impedance-based IC(50) for
      zinc(ii) is 55.5 and 150.8 MUM for PC-3 and PNT1A, respectively. MTT-determined
      IC(50) are >1.3-fold higher. Impedance-based viability correlates with viable
      count (r > 0.92; p < 0.03), not with MTT. Two-fold lower intracellular zinc(ii)
      in the tumour PC-3 cell line was found. After zinc(ii) treatment >2.6-fold
      increase of intracellular zinc(ii) was observed in non-tumour PNT1A and in tumour
      PC-3 cells. In PC-3 cells, free and bound zinc(ii) levels were enhanced more
      markedly as compared to PNT1A. PNT1A produced 4.2-fold less MT compared to PC3.
      PNT1A cells showed a 4.8-fold increase trend (r = 0.94; p = 0.005); PC-3 did show
      a significant trend at MT1 and MT2 protein levels (r = 0.93; p = 0.02) with
      nearly ten-fold increase after 100 MUM zinc(ii) treatment. In terms of redox
      state, PNT1A had a predominance of reduced GSH forms (GSH : GSSG ratio > 1), when
      exposed to zinc(ii) compared to PC3, where predominance of oxidised forms remains
      at all concentrations. IC(50) differs significantly when determined by MTT and
      real-time impedance-based assays due to dependence of impedance on cell
      morphology and adhesion. When real-time growth monitoring, precise
      electrochemical methods and fluorescent microscopy are performed together,
      accurate information for metal fluxes, their buffering by thiol compounds and
      monitoring of the redox state become a powerful tool for understanding the role
      of oxidative stress in carcinogenesis.

PMID- 22592804
TI  - Tetraspanin CD151 protects against pulmonary fibrosis by maintaining epithelial
      integrity.
AB  - RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a chronic pulmonary disorder of
      unknown etiology with few treatment options. Although tetraspanins are involved
      in various diseases, their roles in fibrosis have not been determined.
      OBJECTIVES: To investigate the role of tetraspanin CD151 in pulmonary fibrosis.
      METHODS: CD151 knockout (KO) mice were studied by histological, biochemical, and
      physiological analyses and compared with wild-type mice and CD9 KO mice. Further
      mechanistic analyses were performed in vitro, in vivo, and on samples from
      patients with IPF. MEASUREMENTS AND MAIN RESULTS: A microarray study identified
      an enrichment of genes involved in connective tissue disorders in the lungs of
      CD151 KO mice, but not in CD9 KO mice. Consistent with this, CD151 KO mice
      spontaneously exhibited age-related pulmonary fibrosis. Deletion of CD151 did not
      affect pulmonary fibroblast functions but instead degraded epithelial integrity
      via attenuated adhesion strength on the basement membrane; CD151-deleted alveolar
      epithelial cells exhibited increased alpha-SMA expression with activation of p
      Smad2, leading to fibrotic changes in the lungs. This loss of epithelial
      integrity in CD151 KO lungs was further exacerbated by intratracheal bleomycin
      exposure, resulting in severe fibrosis with increased mortality. We also observed
      decreased numbers of CD151-positive alveolar epithelial cells in patients with
      IPF. CONCLUSIONS: CD151 is essential for normal function of alveolar epithelial
      cells; loss of CD151 causes pulmonary fibrosis as a result of epithelial
      disintegrity. Given that CD151 may protect against fibrosis, this protein
      represents a novel target for the treatment of fibrotic diseases.

PMID- 22592806
TI  - Linking surveillance with action against drug-resistant tuberculosis.
AB  - The speed at which most countries with high burdens of multidrug-resistant
      tuberculosis (MDRTB) have scaled up their capacity to diagnose and treat
      individuals with these forms of TB has failed to keep pace with the problem.
      Limited availability of drug susceptibility testing, high costs and
      inefficiencies in the supply of second-line drugs, and inadequate capacity for
      the management of patients with MDRTB have contributed to the wide gap between
      the estimated need for and the delivery of MDRTB treatment. The most recent
      global estimates indicate that only about 1 in 20 individuals with incident MDRTB
      will be properly diagnosed; fewer still receive quality-assured treatment. As
      policy makers confront the threat of growing levels of drug-resistant TB, there
      is a clear role for improved surveillance methods that can facilitate more
      effective public health responses. In countries that cannot yet test all incident
      cases for drug resistance, analysis of programmatic data and use of periodic,
      efficient surveys can provide information to help prioritize the use of limited
      resources to geographic areas or population subgroups of greatest concern. We
      describe methods for the analysis of routinely collected data and alternative
      surveys that can help tighten the link between surveillance activities and
      interventions.

PMID- 22592805
TI  - Macrophage migration inhibitory factor enzymatic activity, lung inflammation, and
      cystic fibrosis.
AB  - RATIONALE: Macrophage migration inhibitory factor (MIF) is a proinflammatory
      mediator with unique tautomerase enzymatic activity; the precise function has not
      been clearly defined. We previously demonstrated that individual patients with
      cystic fibrosis (CF) who are genetically predisposed to be high MIF producers
      develop accelerated end-organ injury. OBJECTIVES: To characterize the effects of
      the MIF-CATT polymorphism in patients with CF ex vivo. To investigate the role of
      MIF's tautomerase activity in a murine model of Pseudomonas aeruginosa infection.
      METHODS: MIF and tumor necrosis factor (TNF)-alpha protein levels were assessed
      in plasma or peripheral blood mononuclear cell (PBMC) supernatants by ELISA. A
      murine pulmonary model of chronic Pseudomonas infection was used in MIF wild-type
      mice (mif(+/+)) and in tautomerase-null, MIF gene knockin mice (mif (P1G/P1G)).
      MEASUREMENTS AND MAIN RESULTS: MIF protein was measured in plasma and PBMCs from
      5- and 6-CATT patients with CF; LPS-induced TNF-alpha production from PBMCs was
      also assessed. The effect of a specific inhibitor of MIF-tautomerase activity,
      ISO-1, was investigated in PBMCs. In the murine infection model, total weight
      loss, differential cell counts, bacterial load, and intraacinar airspace/tissue
      volume were measured. MIF and TNF-alpha levels were increased in 6-CATT compared
      with 5-CATT patients with CF. LPS-induced TNF-alpha production from PBMCs was
      attenuated in the presence of ISO-1. In a murine model of Pseudomonas infection,
      significantly less pulmonary inflammation and bacterial load was observed in
      mif(P1G/P1G) compared with mif(+/+) mice. CONCLUSIONS: MIF-tautomerase activity
      may provide a novel therapeutic target in patients with chronic inflammatory
      diseases such as CF, particularly those patients who are genetically predisposed
      to produce increased levels of this cytokine.

PMID- 22592807
TI  - Suppression of myocardial 18F-FDG uptake with a preparatory "Atkins-style" low
      carbohydrate diet.
AB  - OBJECTIVES: Physiological myocardial uptake of 18F-FDG during positron emission
      tomography can mask adjacent abnormal uptake in mediastinal malignancy and
      inflammatory cardiac diseases. Myocardial uptake is unpredictable and variable.
      This study evaluates the impact of a low-carbohydrate diet in reducing myocardial
      FDG uptake. METHOD: Patients attending for clinically indicated oncological FDG
      PET were asked to have an "Atkins-style" low-carbohydrate diet (less than 3 g)
      the day before examination and an overnight fast. A total of 120 patients
      following low-carbohydrate diet plus overnight fast were compared with 120
      patients prepared by overnight fast alone. Patients having an Atkins-style diet
      also completed a diet compliance questionnaire. SUV(max) and SUV(mean) for
      myocardium, blood pool and liver were measured in both groups. RESULTS:
      Myocardial SUV(max) fell from 3.53 +/- 2.91 in controls to 1.77 +/- 0.91 in the
      diet-compliant group. 98 % of diet-compliant patients had a myocardial SUV(max)
      less than 3.6 compared with 67 % of controls. Liver and blood pool SUV(max) rose
      from 2.68 +/- 0.49 and 1.82 +/- 0.30 in the control group to 3.14 +/- 0.57 and
      2.06 +/- 0.30. CONCLUSION: An Atkins-style diet the day before PET, together with
      an overnight fast, effectively suppresses myocardial FDG uptake. KEY POINTS : *
      Low-carbohydrate diet (LCD) the day before PET suppresses myocardial FDG uptake.
      * LCD before PET increases liver and blood pool SUV ( max ) and SUV ( mean ). *
      Suppression of myocardial uptake may improve PET imaging of thoracic disease. *
      Suppression of myocardial uptake may help imaging cardiac inflammatory disease
      with PET.

PMID- 22592808
TI  - Accuracy, image quality and radiation dose comparison of high-pitch spiral and
      sequential acquisition on 128-slice dual-source CT angiography in children with
      congenital heart disease.
AB  - OBJECTIVES: To compare accuracy, image quality and radiation dose between high
      pitch spiral and sequential modes on 128-slice dual-source computed tomographic
      (DSCT) angiography in children with congenital heart disease (CHD). METHODS:
      Forty patients suspected with CHD underwent 128-slice DSCT angiography with high
      pitch mode and sequential mode respectively. All the anomalies were confirmed by
      the surgical and/or the conventional cardiac angiography (CCA) findings. The
      diagnostic accuracy, the subjective and objective image quality and effective
      radiation doses were compared. RESULTS: There was no significant difference in
      diagnostic accuracy (chi ( 2 ) = 0.963, P > 0.05), the objective parameters for
      image quality (P > 0.05) and the image quality of great vessels (u = 167.500, P >
      0.05) between the two groups. The image quality of intracardiac structures and
      coronary arteries was significantly better in the sequential mode group than that
      in the high-pitch group (u = 112.500 and 100.000, P < 0.05). The mean effective
      dose in high-pitch group (0.17 +/- 0.05 mSv) was significantly lower (t = 5.287,
      P < 0.05) than that in the sequential mode group (0.29 +/- 0.09 mSv).
      CONCLUSIONS: Both the high-pitch and the sequential modes for 128-slice DSCT
      angiography provide high accuracy for the assessment of CHD in children, while
      the high-pitch mode, even with some image quality decrease, further significantly
      lowers the radiation dose. KEY POINTS: * Modern CT provides excellent anatomical
      detail of congenital heart disease. * Dual source CT systems offer high-pitch
      spiral and sequential modes. * The high-pitch mode provides high accuracy for the
      assessment of CHD. * A few images using the high-pitch mode were occasionally
      slightly degraded. * But the high-pitch mode significantly lowers the radiation
      dose.

PMID- 22592809
TI  - One-lung ventilation in infants and small children: blood gas values.
AB  - PURPOSE: We investigated one-lung ventilation (OLV) in pediatric patients under
      10 kg. The feasibility of OLV using either Arndt endobronchial blocker (AEB) or
      mainstem intubation technique is analyzed. Arterial blood gases (ABG) monitored
      throughout the procedures are presented. METHODS: Following IRB approval, a
      retrospective chart review was conducted on 9 patients <=6 months of age and 2
      patients >=12 months of age undergoing lung resections or aortic coarctations.
      For right thoracotomy, a conventional, cuffed, endotracheal tube (ETT) was
      inserted and guided into the left mainstem bronchus with a bronchoscope and the
      left lung was ventilated. For left thoracotomy, an AEB was inserted into the
      trachea 2 cm past the vocal cords and an ETT was placed through the cords
      adjacent to the blockers (extraluminal). A bronchoscope was then inserted through
      the ETT to visualize and manipulate the blocker into the left mainstem bronchus.
      The blocker cuff was inflated slowly under direct vision while the ETT continued
      to ventilate the right, dependent lung. ABG values were collected
      intraoperatively in all cases. RESULTS: One-lung ventilation could be
      accomplished within 15 min in all cases, and lung isolation was successful in all
      patients. All patients were extubated within 12 h of surgery and had an
      uneventful recovery. ABG values revealed modest arterial acidosis and hypercarbia
      and mild acute ventilatory insufficiency. CONCLUSION: The use of extraluminal AEB
      or mainstem intubation for OLV can be successfully completed in infants weighing
      less than 10 kg. OLV may induce acute respiratory pathology; therefore we
      recommend routine intraoperative ABG monitoring for pediatric patients.

PMID- 22592810
TI  - Association between osteoporosis and urinary calculus: evidence from a population
      based study.
AB  - SUMMARY: This population-based case-control analysis investigated the association
      between osteoporosis and prior urinary calculus (UC) in Taiwan. We succeeded in
      detecting an association between osteoporosis and prior UC (adjusted odds ratio =
      1.66). This association was consistent and significant regardless of stone
      location. INTRODUCTION: UC has been demonstrated to be a risk factor for
      osteoporotic fractures, but no studies to date have directly investigated the
      association between UC and osteoporosis. This case-control analysis aimed to
      investigate the association of osteoporosis with prior UC using a population
      based dataset in Taiwan. METHODS: We first identified 39,840 cases >=40 years who
      received their first-time diagnosis of osteoporosis between 2002 and 2009 and
      then randomly selected 79,680 controls. We used conditional logistic regression
      analyses to compute the odds ratio (OR) and the corresponding 95 % confidence
      interval (CI) for having been previously diagnosed with UC between cases and
      controls. RESULTS: The OR of having been previously diagnosed with UC for
      patients with osteoporosis was 1.66 (95 % CI = 1.59-1.73) when compared to
      controls after adjusting for geographic location, urbanization level, type I
      diabetes mellitus, coronary heart disease, hyperlipidemia, rheumatoid arthritis,
      stroke, renal disease, Parkinson's disease, hyperthyroidism, chronic hepatopathy,
      Cushing's syndrome, malabsorption, gastrectomy, obesity, and alcohol
      abuse/alcohol dependence syndrome. The results consistently showed that
      osteoporosis was significantly associated with a previous diagnosis of UC
      regardless of stone location; the adjusted ORs of prior kidney calculus, ureter
      calculus, bladder calculus, and unspecified calculus when compared to controls
      were 1.71 (95 % CI = 1.61-1.81), 1.60 (95 % CI = 1.47-1.74), 1.59 (95 % CI = 1.23
      2.04), and 1.69 (95 % CI = 1.59-1.80), respectively. CONCLUSIONS: This study
      succeeded in detecting an association between osteoporosis and prior UC. In
      addition, our findings were consistent and significant regardless of stone
      location.

PMID- 22592812
TI  - The characterization of self-assembled monolayers on copper surfaces by low
      temperature plasma mass spectrometry.
AB  - We describe direct analysis of self-assembled monolayers (SAMs) on copper
      surfaces by low temperature plasma (LTP) mass spectroscopy (MS). Two kinds of
      SAMs formed from n-dodecylmercaptan (NDM) and l-phenyl-5-mercaptotetrazole (PMTA)
      were prepared on copper by spontaneous chemisorption. With the LTP probe,
      desorption and ionization of the SAMs was easily achieved, and the ions produced
      were introduced into MS for analysis. Characteristic fragment ions from NDM SAMs,
      mainly [M + M - H](+) (M is the NDM molecule) and from PMTA SAMs, mainly [M + H -
      S](+) (M is the PMTA molecule), were both absent in the MS spectra of neat NDM
      and PMTA samples. This provided evidence of the formation of SAMs on copper. As a
      supplementary method, LTP-MS is helpful in obtaining information on the barrier
      properties of SAMs on copper, such as inhibitor efficiency (IE) and the surface
      adsorption concentration of corrosive electrolyte (Gamma*) surrounding copper.
      Aiming for an evaluation of the reliability of LTP-MS, a comparative study of our
      method and the traditional method of cyclic voltammetry (CV) showed a correlation
      coefficient higher than 0.97. In addition, a rough, simple procedure for imaging
      of the distribution of the molecules adsorbed on copper surface was presented.
      The study supplied a rapid and simple method for direct investigation of SAMs on
      copper.

PMID- 22592815
TI  - Light-induced changes of the refractive indices in a colloid of gold
      nanoparticles in a nematic liquid crystal.
AB  - It was shown that irradiation of a nematic liquid crystal doped with metal
      nanoparticles in the visible near the plasmon resonance band led to strong
      thermal changes of the refractive indices. The effect was studied by recording of
      dynamic optical gratings in the colloid. Nanoparticles "worked" as effective nano
      heaters in a matrix causing the order parameter decrease around the particles. A
      large nonlinearity parameter (n (2) ~ 10(-2) cm(2)/kW and fast response (~ 0.7
      ms), with no detectable particles' aggregation and excellent photo- thermo
      stability make these colloids potentially attractive nonlinear optical media.
      Application of a dynamic holography technique allowed measuring the coefficients
      of thermal conductivity of the liquid crystal along the director k (||) = (0.4 +/
      0.02) W m(-1)K(-1) and perpendicular to the director k (?) = (0.2 +/- 0.01) W m(
      1)K(-1).

PMID- 22592813
TI  - Direct infusion electrospray ionization-ion mobility high resolution mass
      spectrometry (DIESI-IM-HRMS) for rapid characterization of potential bioprocess
      streams.
AB  - Direct infusion electrospray ionization - ion mobility - high resolution mass
      spectrometry (DIESI-IM-HRMS) has been utilized as a rapid technique for the
      characterization of total molecular composition in "whole-sample" biomass
      hydrolysates and extracts. IM-HRMS data reveal a broad molecular weight
      distribution of sample components (up to 1100 m/z) and provide trendline
      isolation of feedstock components from those introduced "in process." Chemical
      formulas were obtained from HRMS exact mass measurements (with typical mass error
      less than 5 ppm) and were consistent with structural carbohydrates and other
      lignocellulosic degradation products. Analyte assignments are supported via IM-MS
      collision-cross-section measurements and trendline analysis (e.g., all
      carbohydrate oligomers identified in a corn stover hydrolysate were found to fall
      within 6% of an average trendline). These data represent the first report of
      collision cross sections for several negatively charged carbohydrates and other
      acidic species occurring natively in biomass hydrolysates.

PMID- 22592816
TI  - Dewetting of cellular monolayers.
AB  - We investigate the physical principles of cellular layer stability. We show that
      cohesive cellular layers deposited on non-adhesive substrates are metastable and
      "dewet" by nucleation and growth of dry patches. The dewetting process can be
      induced either chemically by a non-adhesive surface treatment or, unlike simple
      liquids, physically by a decrease in the substrate rigidity. We thus unveil two
      mechanisms by which the integrity of cellular layers can be compromised. We
      interpret the opening dynamics by an analogy with the dewetting of viscous films.
      This analogy can be exploited to estimate parameters characterizing the
      mechanical response of a cellular layer.

PMID- 22592817
TI  - Biaxial surface order dynamics in calamitic nematics.
AB  - Thermotropic nematic materials relax strong distortions by lowering the nematic
      order: the uniaxial symmetry is broken and is locally replaced by biaxial
      domains. We investigated the dynamics of the nematic order near a boundary
      surface of an asymmetric pi-cell submitted to an external electric field, close
      to the electric order reconstruction threshold. An unexpected phenomenon is
      observed close, but below the threshold: the biaxial order spreads on the surface
      inducing a consequent bulk topological behaviour equivalent to the splay-bend
      fast transition allowed by order reconstruction at higher voltage.

PMID- 22592818
TI  - Macrofauna regulate heterotrophic bacterial carbon and nitrogen incorporation in
      low-oxygen sediments.
AB  - Oxygen minimum zones (OMZs) currently impinge upon >1 million km(2) of sea floor
      and are predicted to expand with climate change. We investigated how changes in
      oxygen availability, macrofaunal biomass and retention of labile organic matter
      (OM) regulate heterotrophic bacterial C and N incorporation in the sediments of
      the OMZ-impacted Indian continental margin (540-1100 m; [O(2)]=0.35-15 MUmol l(
      1)). In situ pulse-chase experiments traced (13)C:(15)N-labelled phytodetritus
      into bulk sediment OM and hydrolysable amino acids, including the bacterial
      biomarker D-alanine. Where oxygen availability was lowest ([O(2)]=0.35 MUmol l(
      1)), metazoan macrofauna were absent and bacteria assimilated 30-90% of the
      labelled phytodetritus within the sediment. At higher oxygen levels ([O(2)]=2-15
      MUmol l(-1)) the macrofaunal presence and lower phytodetritus retention with the
      sediment occur concomitantly, and bacterial phytodetrital incorporation was
      reduced and retarded. Bacterial C and N incorporation exhibited a significant
      negative relationship with macrofaunal biomass across the OMZ. We hypothesise
      that fauna-bacterial interactions significantly influence OM recycling in low
      oxygen sediments and need to be considered when assessing the consequences of
      global change on biogeochemical cycles.

PMID- 22592819
TI  - Diversity, abundance and expression of nitrite reductase (nirK)-like genes in
      marine thaumarchaea.
AB  - Ammonia-oxidizing archaea (AOA) are widespread and abundant in aquatic and
      terrestrial habitats and appear to have a significant impact on the global
      nitrogen cycle. Like the ammonia-oxidizing bacteria, AOA encode a gene homologous
      to copper-containing nitrite reductases (nirK), which has been studied very
      little to date. In this study, the diversity, abundance and expression of
      thaumarchaeal nirK genes from coastal and marine environments were investigated
      using two mutually excluding primer pairs, which amplify the nirK variants
      designated as AnirKa and AnirKb. Only the AnirKa variant could be detected in
      sediment samples from San Francisco Bay and these sequences grouped with the nirK
      from Candidatus Nitrosopumilus maritimus and Candidatus Nitrosoarchaeum limnia.
      The two nirK variants had contrasting distributions in the water column in
      Monterey Bay and the California Current. AnirKa was more abundant in the epi- to
      mesopelagic Monterey Bay water column, whereas AnirKb was more abundant in the
      meso- to bathypelagic California Current water. The abundance and community
      composition of AnirKb, but not AnirKa, followed that of thaumarchaeal amoA,
      suggesting that either AnirKa is not exclusively associated with AOA or that
      commonly used amoA primers may be missing a significant fraction of AOA diversity
      in the epipelagic. Interestingly, thaumarchaeal nirK was expressed 10-100-fold
      more than amoA in Monterey Bay. Overall, this study provides valuable new
      insights into the distribution, diversity, abundance and expression of this
      alternative molecular marker for AOA in the ocean.

PMID- 22592820
TI  - Nitrification of archaeal ammonia oxidizers in acid soils is supported by
      hydrolysis of urea.
AB  - The hydrolysis of urea as a source of ammonia has been proposed as a mechanism
      for the nitrification of ammonia-oxidizing bacteria (AOB) in acidic soil. The
      growth of Nitrososphaera viennensis on urea suggests that the ureolysis of
      ammonia-oxidizing archaea (AOA) might occur in natural environments. In this
      study, (15)N isotope tracing indicates that ammonia oxidation occurred upon the
      addition of urea at a concentration similar to the in situ ammonium content of
      tea orchard soil (pH 3.75) and forest soil (pH 5.4) and was inhibited by
      acetylene. Nitrification activity was significantly stimulated by urea
      fertilization and coupled well with abundance changes in archaeal amoA genes in
      acidic soils. Pyrosequencing of 16S rRNA genes at whole microbial community level
      demonstrates the active growth of AOA in urea-amended soils. Molecular
      fingerprinting further shows that changes in denaturing gradient gel
      electrophoresis fingerprint patterns of archaeal amoA genes are paralleled by
      nitrification activity changes. However, bacterial amoA and 16S rRNA genes of AOB
      were not detected. The results strongly suggest that archaeal ammonia oxidation
      is supported by hydrolysis of urea and that AOA, from the marine Group 1.1a
      associated lineage, dominate nitrification in two acidic soils tested.

PMID- 22592821
TI  - Diversity of active aerobic methanotrophs along depth profiles of arctic and
      subarctic lake water column and sediments.
AB  - Methane (CH(4)) emitted from high-latitude lakes accounts for 2-6% of the global
      atmospheric CH(4) budget. Methanotrophs in lake sediments and water columns
      mitigate the amount of CH(4) that enters the atmosphere, yet their identity and
      activity in arctic and subarctic lakes are poorly understood. We used stable
      isotope probing (SIP), quantitative PCR (Q-PCR), pyrosequencing and enrichment
      cultures to determine the identity and diversity of active aerobic methanotrophs
      in the water columns and sediments (0-25 cm) from an arctic tundra lake (Lake
      Qalluuraq) on the north slope of Alaska and a subarctic taiga lake (Lake
      Killarney) in Alaska's interior. The water column CH(4) oxidation potential for
      these shallow (~2 m deep) lakes was greatest in hypoxic bottom water from the
      subarctic lake. The type II methanotroph, Methylocystis, was prevalent in
      enrichment cultures of planktonic methanotrophs from the water columns. In the
      sediments, type I methanotrophs (Methylobacter, Methylosoma and Methylomonas) at
      the sediment-water interface (0-1 cm) were most active in assimilating CH(4),
      whereas the type I methanotroph Methylobacter and/or type II methanotroph
      Methylocystis contributed substantially to carbon acquisition in the deeper (15
      20 cm) sediments. In addition to methanotrophs, an unexpectedly high abundance of
      methylotrophs also actively utilized CH(4)-derived carbon. This study provides
      new insight into the identity and activity of methanotrophs in the sediments and
      water from high-latitude lakes.

PMID- 22592822
TI  - Metabolic specialization and the assembly of microbial communities.
AB  - Metabolic specialization is a general biological principle that shapes the
      assembly of microbial communities. Individual cell types rarely metabolize a wide
      range of substrates within their environment. Instead, different cell types often
      specialize at metabolizing only subsets of the available substrates. What is the
      advantage of metabolizing subsets of the available substrates rather than all of
      them? In this perspective piece, we argue that biochemical conflicts between
      different metabolic processes can promote metabolic specialization and that a
      better understanding of these conflicts is therefore important for revealing the
      general principles and rules that govern the assembly of microbial communities.
      We first discuss three types of biochemical conflicts that could promote
      metabolic specialization. Next, we demonstrate how knowledge about the
      consequences of biochemical conflicts can be used to predict whether different
      metabolic processes are likely to be performed by the same cell type or by
      different cell types. We then discuss the major challenges in identifying and
      assessing biochemical conflicts between different metabolic processes and propose
      several approaches for their measurement. Finally, we argue that a deeper
      understanding of the biochemical causes of metabolic specialization could serve
      as a foundation for the field of synthetic ecology, where the objective would be
      to rationally engineer the assembly of a microbial community to perform a desired
      biotransformation.

PMID- 22592823
TI  - Dye fills reveal additional olfactory tracts in the protocerebrum of wild-type
      Drosophila.
AB  - The antennal lobe (AL) is the primary olfactory center in insect brains. It
      receives sensory input from the olfactory sensory neurons (OSNs) and sends,
      through its projection neurons (PNs), reformatted output to secondary olfactory
      centers, including the mushroom body (MB) calyx and the lateral horn (LH) in the
      protocerebrum. By injecting dye into the AL of wild-type Drosophila, we
      identified previously unknown direct pathways between the AL and the
      ventrolateral, superior medial, and posterior lateral protocerebra. We found that
      most of these areas in the protocerebrum are connected with the AL through
      multiple tracts, suggesting that these areas are sites of convergence for
      olfactory information. Furthermore, areas such as the superior medial
      protocerebrum now appear to receive olfactory output both directly from the AL
      and indirectly from lobes of the MB and the LH, suggesting a degree of functional
      interaction among these areas. We also analyzed the length and number of fibers
      in each tract. We compare our results obtained from wild-type flies with recent
      results from transgenic strains and discuss how information about odorants is
      distributed to multiple protocerebral areas.

PMID- 22592824
TI  - Exploring the potential impact of a reduction in partnership concurrency on HIV
      incidence in rural Uganda: a modeling study.
AB  - BACKGROUND: A number of African countries have planned campaigns against
      concurrency. It will not be possible to separate the effects of a reduction in
      concurrency from other behavior changes when evaluating these campaigns. This
      modeling study explores the potential impact of an intervention to reduce
      partnership concurrency on HIV incidence in contemporary rural Uganda, keeping
      incidence of sex acts and partnerships in the population constant. METHODS: Data
      on demography, sexual behavior, and HIV prevalence from Uganda were used to
      parameterize an individual-based HIV transmission model. Three baseline model
      scenarios were simulated, representing the best estimate of concurrency
      prevalence in this population, and low and high plausible bounds. Interventions
      that reduced concurrency by 20% and 50% between 2010 and 2020 were simulated, and
      the impact on HIV incidence in 2020 was calculated. RESULTS: Data showed 9.6%
      (7.9%-11.4%) of men and 0.2% (0.0%-0.4%) of women reported concurrency in 2008.
      Reducing concurrency had a nonlinear impact on HIV incidence. A 20% reduction in
      concurrency reduced HIV incidence by 4.1% (0.3%-5.7%) in men and 9.2% (2.1%
      16.8%) in women; a 50% reduction in concurrency reduced HIV incidence by 6.0%
      (1.4%-10.8%) in men and 16.2% (6.3%-23.4%) in women. CONCLUSIONS: Interventions
      against concurrency have the potential to reduce HIV incidence and may have a
      higher impact in women than in men. In rural Uganda, overall impact was modest,
      and this study does not provide strong support for the prioritization of
      concurrency as a target for behavior change interventions. However, it may be
      more useful in higher concurrency settings and for reducing HIV incidence in
      women.

PMID- 22592825
TI  - Chlamydia trachomatis infections among women attending prenatal clinics: United
      States, 2004-2009.
AB  - BACKGROUND: Chlamydia screening practices, positivity, and trends from 2004 to
      2009 in publicly funded prenatal clinics have not been described. METHODS: A
      phone-based survey assessing chlamydia screening practices was conducted among a
      random sample of clinics providing prenatal services (prenatal, family planning,
      and integrated clinics: "prenatal clinics") that reported data to the Infertility
      Prevention Project (IPP) in 2008. Using existing IPP data, chlamydia positivity
      and trends were assessed among women aged 15 to 24 years seeking care in any
      prenatal clinic reporting >=3 years of data to IPP from 2004 to 2009. Linear
      trends of the effect of year (a continuous variable) on positivity were evaluated
      using a correlated modeling approach with a random intercept where the unit of
      analysis was the individual clinic performing chlamydia tests (clinic-based
      analysis). Covariates included race, age, test technology, and geography.
      RESULTS: Of 210 sampled clinics, 166 (79%) completed the survey. Of these, 163
      (98.2%) had documented chlamydia screening criteria. Most clinics screened all
      women during their first trimester and reported 100% screening coverage. From
      2004 to 2009, 267,416 tests among women aged 15 to 24 years were reported to IPP
      from eligible prenatal clinics. Overall chlamydia positivity was 8.3%.
      Controlling for all covariates, positivity decreased from 2004 to 2009 (odds
      ratio: 0.93 per year, 95% confidence interval: 0.92, 0.95, 35% decrease overall).
      CONCLUSIONS: The substantial burden of chlamydia among young women tested in
      prenatal clinics reporting data to IPP suggests the continued need for routine
      screening. Decreasing trends from 2004 to 2009 in the IPP prenatal population
      correspond to findings of overall decreasing chlamydia prevalence in the United
      States.

PMID- 22592826
TI  - Young men's preferences for sexually transmitted disease and reproductive health
      services in San Francisco, California.
AB  - We explored STD (sexually transmitted disease) service preferences among 108
      African-American adolescent males recruited from a high-morbidity neighborhood.
      Participants largely preferred to seek care at traditional STD testing venues
      (86.5%) rather than nontraditional venues. Additionally, most males preferred
      receiving STD test results from a clinician (61.1%) rather than online (11.1%) or
      through email or text message (12.0%). These results highlight the need for
      continued strengthening of traditional public health clinics to ensure capacity
      to meet young men's health needs and to improve outreach and access to
      traditional STD services for young men.

PMID- 22592827
TI  - Limiting options:  sex ratios, incarceration rates, and sexual risk behavior
      among people on probation and parole.
AB  - BACKGROUND: To investigate how incarceration may affect risk of acquiring HIV and
      other sexually transmitted infections, we tested associations of ex-offenders'
      sexual risk behavior with the male-female sex ratio and the male incarceration
      rate. METHODS: Longitudinal data from 1287 drug-involved persons on probation and
      parole as part of the Criminal Justice Drug Abuse Treatment Studies were matched
      by county of residence with population factors, and stratified by race/ethnicity
      and gender. Generalized estimating equations assessed associations of having
      unprotected sex with a partner who had HIV risk factors, and having >1 sex
      partner in the past month. RESULTS: Among non-Hispanic black men and women, low
      sex ratios were associated with greater risk of having unprotected sex with a
      risky partner (adjusted relative risk [ARR] = 1.76, 95% confidence interval [CI]
      = 1.29, 2.42; ARR = 2.48, 95% CI = 1.31, 4.73, respectively). Among non-Hispanic
      black and non-Hispanic white (NHW) women, low sex ratios were associated with
      having >1 sex partner (ARR = 2.00, 95% CI = 1.02, 3.94; ARR = 1.71, 95% CI =
      1.06, 2.75, respectively). High incarceration rates were associated with greater
      risk of having a risky partner for all men (non-Hispanic black: ARR = 2.14, 95%
      CI = 1.39, 3.30; NHW: ARR = 1.39, 95% CI: 1.05, 1.85; Hispanic: ARR = 3.99, 95%
      CI = 1.55, 10.26) and having >1 partner among NHW men (ARR = 1.92, 95% CI = 1.40,
      2.64). CONCLUSIONS: Low sex ratios and high incarceration rates may influence the
      number and risk characteristics of sex partners of ex-offenders. HIV-prevention
      policies and programs for ex-offenders could be improved by addressing structural
      barriers to safer sexual behavior.

PMID- 22592828
TI  - High HIV incidence and socio-behavioral risk patterns in fishing communities on
      the shores of Lake Victoria, Uganda.
AB  - BACKGROUND: We report on HIV acquisition and its associated risk factors in 5
      fishing communities on the shores of Lake Victoria in Uganda. A cohort of 1000
      HIV-uninfected at-risk volunteers aged 13 to 49 years were recruited in 2009 and
      followed up for 18 months. METHODS: At enrollment and semiannual visits, socio
      demographic and risk behavior data were collected through a structured
      questionnaire and blood samples tested for HIV and syphilis. Detailed life
      histories were collected from 78 volunteers using in-depth interviews. RESULTS:
      Of the 1000 volunteers enrolled, 919 (91.9%) were followed up, with 762 (76.2%)
      reaching the study end points (either seroconverted or completed 4 visits). There
      were 59 incident cases in 1205.6 person-years at risk (PYAR), resulting in an
      incidence rate of 4.9 (95% CI = 3.8 to 6.3) per 100 PYAR. The highest HIV
      incidence rates were among those working in bars (9.8/100 PYAR [4.7-20.6]),
      protestants (8.6/100 PYAR [5.8-12.7]), those aged 13 to 24 years (7.5/100 PYAR
      [5.2-11.0]), and new immigrants (6.6/100 PYAR [4.9-8.9]). HIV infection was
      independently associated with being young (adjusted hazard ratio (aHR) = 2.5 [95%
      CI = 1.3-4.9]), reporting genital sores/discharge recently (aHR = 2.8 [1.6-5.0]),
      regular alcohol consumption (aHR = 3.3 [1.6-6.1]), use of marijuana (aHR = 2.9
      [1.0-8.0]), cigarette smoking (aHR = 3.6 [1.4-9.3]), and religion (compared with
      Catholics, Protestants had aHR = 2.7 [1.4-5.3] and Muslims had aHR = 2.3 [1.1
      4.8]). CONCLUSIONS: These fishing communities experienced high HIV infection,
      which was mainly explained by high-risk behavior. There is an urgent need to
      target HIV prevention and research efforts to this vulnerable and neglected
      group.

PMID- 22592830
TI  - The 2010 Health Care Act and barriers to effective health promotion among men who
      have sex with men.

PMID- 22592829
TI  - Results of a 25-year longitudinal analysis of the serologic incidence of syphilis
      in a cohort of HIV-infected patients with unrestricted access to care.
AB  - BACKGROUND: The well-described biologic and epidemiologic associations of
      syphilis and HIV are particularly relevant to the military, as service members
      are young and at risk for sexually transmitted infections. We therefore used the
      results of serial serologic testing to determine the prevalence, incidence, and
      risk factors for incident syphilis in a cohort of HIV-infected Department of
      Defense beneficiaries. METHODS: Participants with a positive nontreponemal test
      at HIV diagnosis that was confirmed on treponemal testing were categorized as
      prevalent cases, and participants with an initial negative nontreponemal test who
      subsequently developed a confirmed positive nontreponemal test were categorized
      as incident cases. RESULTS: At HIV diagnosis, the prevalence of syphilis was 5.8%
      (n = 202). A total of 4239 participants contributed 27,192 person-years (PY) to
      the incidence analysis and 347 (8%) developed syphilis (rate, 1.3/100 PY; [1.1,
      1.4]). Syphilis incidence was highest during the calendar years 2006 to 2009
      (2.5/100 PY; [2.0, 2.9]). In multivariate analyses, younger age (per 10 year
      increase hazard ratio [HR], 0.8; [0.8-0.9]), male gender (HR, 5.6; [2.3-13.7]),
      non-European-American ethnicity (African-American HR, 3.2; [2.5-4.2]; Hispanic
      HR, 1.9; [1.2-3.0]), and history of hepatitis B (HR, 1.5; [1.2-1.9]) or gonorrhea
      (HR, 1.4; [1.1-1.8]) were associated with syphilis. CONCLUSIONS: The significant
      burden of disease both at and after HIV diagnosis, observed in this cohort,
      suggests that the cost-effectiveness of extending syphilis screening to at-risk
      military members should be assessed. In addition, HIV-infected persons continue
      to acquire syphilis, emphasizing the continued importance of prevention for
      positive programs.

PMID- 22592831
TI  - The rapid plasma reagin test cannot replace the venereal disease research
      laboratory test for neurosyphilis diagnosis.
AB  - BACKGROUND: The cerebrospinal fluid (CSF) Venereal Disease Research Laboratory
      (VDRL) test is a mainstay for neurosyphilis diagnosis, but it lacks diagnostic
      sensitivity and is logistically complicated. The rapid plasma reagin (RPR) test
      is easier to perform, but its appropriateness for use on CSF is controversial.
      METHODS: RPR reactivity was determined for CSF from 149 individuals with syphilis
      using 2 methods. The CSF-RPR was performed according to the method for serum. The
      CSF-RPR-V was performed using the method recommended for the CSF-VDRL. Laboratory
      defined neurosyphilis included reactive CSF-fluorescent treponemal antibody
      absorption test and CSF white blood cells >20/uL. Symptomatic neurosyphilis was
      defined as vision loss or hearing loss. RESULTS: CSF-VDRL was reactive in 45
      (30.2%) patients. Of these, 29 (64.4%) were CSF-RPR reactive and 37 (82.2%) were
      CSF-RPR-V reactive. There were no instances where the CSF-VDRL was nonreactive
      but the CSF-RPR or CSF-RPR-V was reactive. Among the 28 samples that were
      reactive in all 3 tests, CSF-VDRL titers (median [IQR], 1:4 [1:4-1:16]) were
      significantly higher than CSF-RPR (1:2 [1:1-1:4], P = 0.0002) and CSF-RPR-V
      titers (1:4 [1:2-1:8], P = 0.01). The CSF RPR and the CSF-RPR-V tests had lower
      sensitivities than the CSF-VDRL: 56.4% and 59.0% versus 71.8% for laboratory
      diagnosed neurosyphilis and 51.5% and 57.6% versus 66.7% for symptomatic
      neurosyphilis. CONCLUSIONS: Compared with the CSF-VDRL, the CSF-RPR has a high
      false-negative rate, thus not improving upon this known limitation of the CSF
      VDRL for neurosyphilis diagnosis. Adapting the RPR procedure to mimic the CSF
      VDRL decreased, but did not eliminate, the number of false negatives and did not
      avoid all the logistical complications of the CSF-VDRL.

PMID- 22592832
TI  - Disparities in sexually transmitted disease rates across the "eight Americas".
AB  - BACKGROUND: The purpose of this study was to examine rates of 3 bacterial
      sexually transmitted diseases (STDs; syphilis, gonorrhea, and chlamydia) in 8
      subpopulations (known as the "eight Americas") defined by race and a small number
      of county-level sociodemographic and geographical characteristics. The eight
      Americas are (1) Asians and Pacific Islanders in specific counties; (2) Northland
      low-income rural white; (3) Middle America; (4) Low-income whites in Appalachia
      and Mississippi Valley; (5) Western Native American; (6) Black middle America;
      (7) Southern low-income rural black; and (8) High-risk urban black. METHODS: A
      list of the counties comprising each of the eight Americas was obtained from the
      corresponding author of the original eight Americas project, which examined
      disparities in mortality rates across the eight Americas. Using county-level STD
      surveillance data, we calculated syphilis, gonorrhea, and chlamydia rates (new
      cases per 100,000) for each of the eight Americas. RESULTS: Reported STD rates
      varied substantially across the eight Americas. STD rates were generally lowest
      in Americas 1 and 2 and highest in Americas 6, 7, and 8. CONCLUSIONS: Although
      disparities in STDs across the eight Americas are generally similar to the well
      established disparities in STDs across race/ethnicity, the grouping of counties
      into the eight Americas does offer additional insight into disparities in STDs in
      the United States. The high STD rates we found for black Middle America are
      consistent with the assertion that sexual networks and social factors are
      important drivers of racial disparities in STDs.

PMID- 22592833
TI  - Colposcopy:  still useful in microbicide safety trials?
AB  - BACKGROUND: Colposcopy is used to evaluate vaginal microbicides, but its link to
      risk of HIV is unknown. This reanalysis of 9 safety studies determined the impact
      of omitting colposcopy on the number of findings detected and assessed whether
      colposcopy was useful in identifying nonoxynol-9 (N-9) as an unsafe product in
      one study. METHODS: Product-related findings seen with naked eye and colposcopy
      or by colposcopy alone were evaluated. Using data from one study, the ratio of
      findings in N-9 users to those in hydroxyethylcellulose (HEC) users was compared
      for findings seen by naked eye and colposcopy versus findings detected only by
      colposcopy. RESULTS: Of the 403 finding observations in the 9 studies, 173 (43%)
      would have been missed without colposcopy. Data from the N-9/HEC study showed
      that without colposcopy, there would have been 7 times as many observations in
      the N-9 group as in the HEC group (63 vs. 9). With colposcopy, the N-9/HEC ratio
      was 13:9 or 1.4. Considering epithelial integrity, finding type, and size showed
      similar patterns, except that among the smallest findings (<5 mm), the N-9/HEC
      ratio was 1.2 by naked eye and nearly the same at 1.4 by colposcopy. CONCLUSION:
      Colposcopy was not helpful in identifying an unsafe product: the conclusions
      reached using naked eye examination alone were more alarming regarding the safety
      of N-9 than reached by including colposcopy. Recommendations include: (1) naked
      eye examinations should be continued in microbicide studies; (2) colposcopy may
      be considered for early studies, such as first-in-human studies, but has no place
      in large studies; and (3) colposcopy should be replaced as soon as possible with
      a more objective validated biomarker of HIV risk.

PMID- 22592835
TI  - CHIAS: a standardized measure of parental HPV immunization attitudes and beliefs
      and its associations with vaccine uptake.
AB  - BACKGROUND: Despite the burden of human papillomavirus (HPV)-associated
      morbidity, less than half of US adolescent females had begun the 3-dose HPV
      vaccination series as of 2010. Given that parental attitudes significantly
      influence vaccine uptake, having a standardized measure of parental beliefs that
      predict HPV vaccine uptake would contribute substantially to the development of
      effective immunization strategies. We explored whether a modified version of the
      previously published Carolina HPV Immunization Attitudes and Beliefs Scale
      (CHIAS) could be applied nationally to identify attitudinal constructs that were
      associated with HPV vaccine uptake and maternal HPV vaccination intention.
      METHODS: We administered the modified CHIAS as part of a cross-sectional, web
      based survey to a nationally representative sample of mothers of adolescent
      females. Exploratory factor analysis was used to identify underlying attitudinal
      constructs, which were compared with those identified in the original CHIAS.
      Bivariate and multivariate analyses determined associations between these
      attitudinal constructs and HPV vaccine uptake as well as vaccination intention.
      RESULTS: Overall survey response rate was 57%. The modified CHIAS yielded a
      factor structure that was similar to the original CHIAS, identifying 3
      attitudinal constructs: harms/ineffectiveness, barriers, and social norms. In
      multivariate models, harms/ineffectiveness and social norms were independently
      associated with HPV vaccine uptake. CONCLUSIONS: The CHIAS seems to be a valid
      instrument for identifying important factors associated with HPV-vaccine uptake
      and parental vaccination intention nationally. Longitudinal studies are merited
      to explore whether these attitudinal constructs also reliably predict HPV-vaccine
      uptake.

PMID- 22592834
TI  - Routine brief risk-reduction counseling with biannual STD testing reduces STD
      incidence among HIV-infected men who have sex with men in care.
AB  - BACKGROUND: We evaluated whether routine biannual sexually transmitted disease
      (STD) testing coupled with brief risk-reduction counseling reduces STD incidence
      and high-risk behaviors. METHODS: The SUN study is a prospective observational
      HIV cohort study conducted in 4 US cities. At enrollment and every 6 months
      thereafter, participants completed a behavioral survey and were screened for
      STDs, and if diagnosed, were treated. Medical providers conducted brief risk
      reduction counseling with all patients. Among men who have sex with men (MSM), we
      examined trends in STD incidence and rates of self-reported risk behaviors before
      and after exposure to the risk-reduction intervention. The "preintervention"
      visit was the study visit that was at least 6 months after enrollment STD
      screening and treatment and at which the participant was first exposed to the
      intervention. The "postintervention" visit was 12 months later. RESULTS: Among
      216 MSM with complete STD and behavioral data, median age was 44.5 years; 77%
      were non-Hispanic white; 83% were on highly active antiretroviral treatment; 84%
      had an HIV RNA level <400 copies/mL and the median CD4 (cluster of
      differentiation 4) count was 511 cells/mm. Twelve months after first exposure to
      the risk-reduction intervention, STD incidence declined from 8.8% to 4.2% (P =
      0.041). Rates of unprotected receptive or insertive anal intercourse with HIV
      positive partners increased (19% to 25%, P = 0.024), but did not change with HIV
      negative partners or partners of unknown HIV status (24% to 22%, P = 0.590).
      CONCLUSIONS: STD incidence declined significantly among HIV-infected MSM after
      implementing frequent, routine STD testing coupled with risk-reduction
      counseling. These findings support adoption of routine STD screening and risk
      reduction counseling for HIV-infected MSM.

PMID- 22592836
TI  - Sentinel surveillance for pharyngeal chlamydia and gonorrhea among men who have
      sex with men--San Francisco, 2010.
AB  - BACKGROUND: Although a potentially important route for transmission, limited data
      exist on the burden of pharyngeal chlamydia (CT) and gonorrhea (GC) among men who
      have sex with men (MSM). We examined pharyngeal CT and GC among MSM screened in
      San Francisco in 2010. METHODS: MSM seeking services in a variety of clinical
      settings provided clinician-collected pharyngeal specimens that were tested using
      the APTIMA Combo 2 platform. The prevalence of pharyngeal CT and GC was estimated
      at 5 sentinel sites: the municipal STD clinic, a gay men's health clinic, an HIV
      care clinic, an HIV testing site, and primary care clinics supported by the San
      Francisco Department of Public Health. Positivity for each infection was
      calculated as the number of positive tests divided by the number of testers with
      corresponding confidence intervals (CI). RESULTS: In 2010, a total of 12,454
      pharyngeal CT specimens and 12,457 pharyngeal GC specimens were tested for an
      overall CT positivity of 1.69% (95% CI: 1.47-1.93) and GC positivity of 5.76%
      (95% CI: 5.36-6.19). At the 5 sentinel sites, pharyngeal CT positivity ranged
      from 1.10% (HIV testing site) to 2.28% (STD clinic); pharyngeal GC positivity
      ranged from 3.4% (HIV testing site) to 7.01% (STD clinic). CONCLUSION: Sentinel
      surveillance data indicate that there is a substantial burden of pharyngeal CT
      and GC infections among MSM in San Francisco. Identification and treatment of
      pharyngeal infections could prevent ongoing transmission of these bacteria.
      Increasing access to nucleic acid amplification tests-based pharyngeal screening
      should be a public health priority.

PMID- 22592837
TI  - A syphilis-positive organ donor -- management of the cardiac transplant
      recipient: a case report and review of the literature.
AB  - Syphilis as a public health problem has not been resolved. Because donor organs
      are scarce, Treponema pallidum seropositivity is no longer considered a
      contraindication to transplant. However, there is little guidance on the
      management and monitoring on the recipient of organs from patients with syphilis.
      We present a case of a patient successfully transplanted with a heart from a
      seropositive donor and a review of the literature.

PMID- 22592838
TI  - Clinical characteristics associated with Mycoplasma genitalium infection among
      women at high risk of HIV and other STI in Uganda.
AB  - BACKGROUND: Mycoplasma genitalium is a common infection of the genitourinary
      tract, but its pathogenic effects have not been well described, especially in
      women. The increasing evidence that M. genitalium is associated with HIV
      infection calls for an urgent consensus on how best to control this infection.
      The aim of this study was to describe symptoms and signs associated with M.
      genitalium infection among high-risk women in Uganda. METHODS: A cohort of 1027
      female sex workers was recruited in Kampala in 2008. At enrollment, HIV testing
      was performed, genital specimens were tested for other sexually transmitted
      infection, and urogenital symptoms and signs were recorded. Endocervical swabs
      were tested for M. genitalium using a commercial Real-TM PCR assay (Sacace
      Biotechnologies, Como, Italy). The associations of clinical signs and symptoms
      with prevalent M. genitalium were investigated using multivariable logistic
      regression models. RESULTS: Reported dysuria and presence of mucopurulent vaginal
      discharge were significantly associated with M. genitalium infection (OR: 1.85,
      95% confidence interval: 1.13-3.03 and OR: 1.55, 95% confidence interval: 1.06
      2.29, respectively). There was little evidence for an association with cervicitis
      or with pelvic inflammatory disease. CONCLUSIONS: In this specific population, we
      found evidence that symptoms of urethritis and mucopurulent vaginal discharge
      were associated with M. genitalium infection. This supports earlier studies
      showing that M. genitalium may lead to clinically relevant genitourinary
      disorders and should be treated. In the absence of sensitive screening tests,
      further work is needed to validate clinical findings as possible indicators of M.
      genitalium infection to guide a possible syndromic approach for its control.

PMID- 22592839
TI  - Risk-based HIV testing of men who have sex with men would result in missed HIV
      diagnoses.

PMID- 22592841
TI  - Distribution of the glycine receptor beta-subunit in the mouse CNS as revealed by
      a novel monoclonal antibody.
AB  - Inhibitory glycine receptors (GlyRs) are composed of homologous alpha- (alpha1-4)
      and beta-subunits. The beta-subunits (GlyRbeta) interact via their large
      cytosolic loops with the postsynaptic scaffolding protein gephyrin and are
      therefore considered essential for synaptic localization. In situ hybridization
      studies indicate a widespread distribution of GlyRbeta transcripts throughout the
      mammalian central nervous system (CNS), whereas GlyRalpha mRNAs and proteins
      display more restricted expression patterns. Here we report the generation of a
      monoclonal antibody that specifically recognizes rodent GlyRbeta (mAb-GlyRbeta)
      and does not exhibit crossreactivity with any of the GlyRalpha1-4 subunits.
      Immunostaining with this antibody revealed high densities of punctate GlyRbeta
      immunoreactivity at inhibitory synapses in mouse spinal cord, brainstem,
      midbrain, and olfactory bulb but not in the neocortex, cerebellum, or
      hippocampus. This contrasts the abundance of GlyRbeta transcripts in all major
      regions of the rodent brain and suggests that GlyRbeta protein levels are
      regulated posttranscriptionally. When mAb-GlyRbeta was used in double-labeling
      experiments with GlyRalpha1-, alpha2-, alpha3-, or alpha4-specific antibodies to
      examine the colocalization of GlyRbeta with these GlyR subunits in the mouse
      retina, >90% of the GlyRalpha1-3 clusters detected were found to be GlyRbeta
      immunoreactive. A subset (about 50%) of the GlyRalpha4 puncta in the inner
      plexiform layer, however, was found to lack GlyRbeta and gephyrin immunostaining.
      These GlyRalpha4-only clusters were apposed to bassoon immunoreactivity and hence
      synaptically localized. Their existence points to a gephyrin-independent synaptic
      localization mechanism for a minor subset of GlyRs.

PMID- 22592840
TI  - Neuroanatomic connectivity of the human ascending arousal system critical to
      consciousness and its disorders.
AB  - The ascending reticular activating system (ARAS) mediates arousal, an essential
      component of human consciousness. Lesions of the ARAS cause coma, the most severe
      disorder of consciousness. Because of current methodological limitations,
      including of postmortem tissue analysis, the neuroanatomic connectivity of the
      human ARAS is poorly understood. We applied the advanced imaging technique of
      high angular resolution diffusion imaging (HARDI) to elucidate the structural
      connectivity of the ARAS in 3 adult human brains, 2 of which were imaged
      postmortem. High angular resolution diffusion imaging tractography identified the
      ARAS connectivity previously described in animals and also revealed novel human
      pathways connecting the brainstem to the thalamus, the hypothalamus, and the
      basal forebrain. Each pathway contained different distributions of fiber tracts
      from known neurotransmitter-specific ARAS nuclei in the brainstem. The
      histologically guided tractography findings reported here provide initial
      evidence for human-specific pathways of the ARAS. The unique composition of
      neurotransmitter-specific fiber tracts within each ARAS pathway suggests
      structural specializations that subserve the different functional characteristics
      of human arousal. This ARAS connectivity analysis provides proof of principle
      that HARDI tractography may affect the study of human consciousness and its
      disorders, including in neuropathologic studies of patients dying in coma and the
      persistent vegetative state.

PMID- 22592842
TI  - Oral anticoagulation and VKORC1 polymorphism in patients with a mechanical heart
      prosthesis: a 6-year follow-up.
AB  - Therapy with Vitamin K antagonists (VKA) effectively reduces the thrombosis risk
      in many clinical conditions. Genetic variants of vitamin K epoxide reductase
      (VKORC-1) are associated with increased VKA effect and bleeding risk. It is
      unknown whether these variants could also affect the long-term outcome in
      patients with high-dosage oral anticoagulation and/or more difficult adherence to
      the therapeutic INR range. Hundred and twenty-four patients with mechanical heart
      valve replacement assuming VKA were genotyped for VKORC-1 -1639G>A (Rs9923231)
      polymorphism. Hemorrhage, venous thrombosis and atherothrombotic events were
      retrospectively assessed for a 6-year period. Furthermore, stability of their INR
      in relationship with the VKORC-1 genotype was investigated day-by-day for 3
      months. No differences were observed in hemorrhage and venous thrombosis events
      according to rs 9923231. GG genotype carriers (n = 41) had no atherothrombotic
      events, while 4 strokes, 4 TIA and 3 AMI were diagnosed in A carriers (n = 83; P
      = 0.0008). During the daily observation period, A allele carriers had lower VKA
      requirements (4.7, 3.7, 2.2 mg/day for GG/GA/AA genotype respectively; P =
      0.00001), higher mean INR (2.7, 2.8, 2.9; P = 0.05) and a higher number of
      examinations above the therapeutic range than GG carriers (17 % vs. 0 % in GG
      genotype, P = 0.036). Conversely, patients with GG genotype had a more stable
      dosage of VKA (P = 0.006) and a higher percentage of examinations under the
      therapeutic range (51, 43 and 36 % in GG, GA and AA genotype, respectively, P =
      0.040). In patients with high dosage VKA, VKORC-1 polymorphism is associated to a
      different warfarin dosage, anticoagulation level, time spent outside the
      therapeutic range and, in the long-term, a different incidence of
      atherothrombotic events.

PMID- 22592843
TI  - Livedoid vasculopathy in a patient with lupus anticoagulant and MTHFR mutation:
      treatment with low-molecular-weight heparin.
AB  - Livedoid vasculopathy is characterized by painful purpuric lesions on the
      extremities which frequently ulcerate and heal with atrophic scarring. For many
      years, livedoid vasculopathy has been considered to be a primary vasculitic
      process. However, there has been evidence considering livedoid vasculopathy as an
      occlusive vasculopathy due to a hypercoagulable state. We present the case of
      livedoid vasculopathy in a 21-year-old female who had been suffering of painful
      lower extremity lesions of 3 years duration. The patient was found to be lupus
      anticoagulant positive and homozygous for methylenetetrahydrofolate reductase
      C677T mutation. The patient was successfully treated with low-molecular-weight
      heparin.

PMID- 22592844
TI  - Hair mercury concentrations of lactating mothers and breastfed infants in Iran
      (fish consumption and mercury exposure).
AB  - Coastal populations with high seafood consumption in the South Caspian Sea (Iran)
      have a significant exposure to dietary mercury. This study assesses the
      biomonitoring of mercury in mothers and breastfed infants in the South Caspian
      Sea. The mean of mercury concentration in the hair of 93 pairs of mothers and
      infants was obtained and was 3.55 and 1.89 MUg g(-1), respectively. A
      statistically significant correlation (R = 0.850, P = 0.000) was seen between
      mercury concentration in the hair of mothers and infants. The results of this
      study indicate that hair mercury concentrations exceeded the USEPA reference dose
      of 1 MUg g(-1) in 82.7 % of mothers and 61.2 % of infants. Also, 31 % of the
      mothers and 10.7 % of the infants had mercury concentrations more than the WHO
      "threshold" level (5 MUg g(-1)). The age and fish consumption of mothers were the
      factors that significantly affected the hair mercury concentration of mothers and
      infants. Number of dental amalgam fillings of mothers was the factor that only
      affected mercury in the hair of mothers. According to the results, we can
      conclude that the main determinant of mercury exposure was the intake of mercury
      through fish consumption of mothers.

PMID- 22592845
TI  - Reference values for serum zinc concentration and prevalence of zinc deficiency
      in adult Iranian subjects.
AB  - Zinc, as an essential trace element for health, plays various biological roles in
      human body functions. Serum zinc reference values are essential for assessing
      zinc-associated abnormalities and the prevalence of zinc deficiency. This study
      aims at determining age- and sex-specific reference values for serum zinc
      concentrations in adult Iranian subjects. Serum zinc concentration was measured
      by flame atomic absorption spectrometry in 4,698 adult subjects, aged 20-94
      years, randomly selected from the population of the Tehran, Lipid, and Glucose
      Study. After application of exclusion criteria, reference values for serum zinc
      were determined in 2,632 apparently healthy subjects according to guidelines of
      the International Federation of Clinical Chemistry (nonparametric method).
      Dietary zinc was assessed in 2,906 individuals, of which 1,685 were healthy
      subjects, using a validated semiquantitative food frequency questionnaire.
      Reference values for serum zinc concentrations ranged between 9.6 and 31.6, 8.9
      and 29.9, and 9.3 and 30.8 MUmol/L in men, women, and the total population,
      respectively. Prevalence of serum zinc deficiency was 3.0 and 2.4 % in men and
      women, respectively (p = 0.267); in men, but not in women, the prevalence
      increased significantly with age (p for trend <0.001). Of the total participants,
      10.3 % (6.5 men and 3.8 % women, p < 0.01) had lower zinc intake compared to
      dietary reference intakes. The zinc density of the population was 6.3 mg/1,000
      kcal. In conclusion, this study presents reference values for serum zinc
      concentration in adult Iranian subjects for both sexes and different age groups.
      Prevalence of serum zinc deficiency and dietary zinc inadequacy seems to be lower
      in Iranians, compared to some other populations.

PMID- 22592847
TI  - Pancreatic adenocarcinoma.

PMID- 22592846
TI  - Ionizing radiations increase the activity of the cell surface glycohydrolases and
      the plasma membrane ceramide content.
AB  - We detected significant levels of beta-glucosidase, beta-galactosidase, sialidase
      Neu3 and sphingomyelinase activities associated with the plasma membrane of
      fibroblasts from normal and Niemann-Pick subjects and of cells from breast,
      ovary, colon and neuroblastoma tumors in culture. All of the cells subjected to
      ionizing radiations showed an increase of the activity of plasma membrane beta
      glucosidase, beta-galactosidase and sialidase Neu3, in addition of the well known
      increase of activity of plasma membrane sphingomyelinase, under similar
      conditions. Human breast cancer cell line T47D was studied in detail. In these
      cells the increase of activity of beta-glucosidase and beta-galactosidase was
      parallel to the increase of irradiation dose up to 60 Gy and continued with time,
      at least up to 72 h from irradiation. beta-glucosidase increased up to 17 times
      and beta-galactosidase up to 40 times with respect to control. Sialidase Neu3 and
      sphingomyelinase increased about 2 times at a dose of 20 Gy but no further
      significant differences were observed with increase of radiation dose and time.
      After irradiation, we observed a reduction of cell proliferation, an increase of
      apoptotic cell death and an increase of plasma membrane ceramide up to 3 times,
      with respect to control cells. Tritiated GM3 ganglioside has been administered to
      T47D cells under conditions that prevented the lysosomal catabolism. GM3 became
      component of the plasma membranes and was transformed into LacCer, GlcCer and
      ceramide. The quantity of ceramide produced in irradiated cells was about two
      times that of control cells.

PMID- 22592849
TI  - David Southall: anatomy of a wrecked career.

PMID- 22592850
TI  - The British government's Troubled Families Programme.

PMID- 22592851
TI  - Experts launch Europe-wide drive to highlight dangers of alcohol.

PMID- 22592852
TI  - Discrimination against doctors with HIV must end.

PMID- 22592853
TI  - Induced hydrophobic recovery of oxygen plasma-treated surfaces.
AB  - Plasma treatment is a widely used method in microfabrication laboratories and the
      plasticware industry to functionalize surfaces for device bonding and preparation
      for mammalian cell culture. However, spatial control of plasma treatment is
      challenging because it typically requires a tedious masking step that is prone to
      alignment errors. Currently, there are no available methods to actively revert a
      surface from a treated hydrophilic state to its original hydrophobic state. Here,
      we describe a method that relies on physical contact treatment (PCT) to actively
      induce hydrophobic recovery of plasma-treated surfaces. PCT involves applying
      brushing and peeling processes with common wipers and tapes to reverse the
      wettability of hydrophilized surfaces while simultaneously preserving
      hydrophilicity of non-contacted surfaces. We demonstrate that PCT is a user
      friendly method that allows 2D and 3D surface patterning of hydrophobic regions,
      and the protection of hydrophilic surfaces from unwanted PCT-induced recovery.
      This method will be useful in academic and industrial settings where plasma
      treatment is frequently used.

PMID- 22592854
TI  - Neighboring Deschampsia flexuosa and Trientalis europaea harbor contrasting root
      fungal endophytic communities.
AB  - Fungal endophytic communities and potential host preference of root-inhabiting
      fungi of boreal forest understory plants are poorly known. The objective of this
      study was to find out whether two neighboring plant species, Deschampsia flexuosa
      (Poaceae) and Trientalis europaea (Primulaceae), share similar root fungal
      endophytic communities and whether the communities differ between two sites. The
      study was carried out by analysis of pure culture isolates and root fungal
      colonization percentages. A total of 84 isolates from D. flexuosa and 27 isolates
      from T. europaea were obtained. The roots of D. flexuosa harbored 16 different
      isolate types based on macromorphological characteristics, whereas only 4 isolate
      types were found in T. europaea. The root colonization by dark septate and
      hyaline septate hyphae correlated with isolate numbers being higher in D.
      flexuosa compared to T. europaea. The different isolate types were further
      identified on the basis of internal transcribed spacer sequence and phylogenetic
      analysis. An isolate type identified as dark septate endophyte Phialocephala
      fortinii colonized 50 % of the T. europaea and 21 % of the D. flexuosa specimens.
      In addition, Meliniomyces variabilis, Phialocephala sphaeroides, and Umbelopsis
      isabellina were found colonizing the grass, D. flexuosa, for the first time and
      Mycena sp. was confirmed as an endophyte of D. flexuosa. Site-specific
      differences were observed in the abundance and diversity of endophytic fungi in
      the roots of both study plants, but the differences were not as predominant as
      those between plant species. It is concluded that D. flexuosa harbors both higher
      amount and more diverse community of endophytic fungi in its roots compared to T.
      europaea.

PMID- 22592855
TI  - Ectomycorrhizal fungi of exotic pine plantations in relation to native host trees
      in Iran: evidence of host range expansion by local symbionts to distantly related
      host taxa.
AB  - Introduction of exotic plants change soil microbial communities which may have
      detrimental ecological consequences for ecosystems. In this study, we examined
      the community structure and species richness of ectomycorrhizal (EcM) fungi
      associated with exotic pine plantations in relation to adjacent native
      ectomycorrhizal trees in Iran to elucidate the symbiont exchange between
      distantly related hosts, i.e. Fagales (Fagaceae and Betulaceae) and Pinaceae. The
      combination of morphological and molecular identification approaches revealed
      that 84.6 % of species with more than one occurrence (at least once on pines)
      were shared with native trees and only 5.9 % were found exclusively on pine root
      tips. The community diversity of ectomycorrhizal fungi in the pine plantations
      adjacent to native EcM trees was comparable to their adjacent native trees, but
      the isolated plantations hosted relatively a species-poor community. Specific
      mycobionts of conifers were dominant in the isolated plantation while rarely
      found in the plantations adjacent to native EcM trees. These data demonstrate the
      importance of habitat isolation and dispersal limitation of EcM fungi in their
      potential of host range expansion. The great number of shared and possibly
      compatible symbiotic species between exotic Pinaceae and local Fagales (Fagaceae
      and Betulaceae) may reflect their evolutionary adaptations and/or ancestral
      compatibility with one another.

PMID- 22592858
TI  - Magnetic field perception in the rainbow trout Oncorynchus mykiss: magnetite
      mediated, light dependent or both?
AB  - In the present study, we demonstrate the role of the trigeminal system in the
      perception process of different magnetic field parameters by heartbeat
      conditioning, i.e. a significantly longer interval between two consecutive
      heartbeats after magnetic stimulus onset in the salmonid fish Oncorhynchus
      mykiss. The electrocardiogram was recorded with subcutaneous silver wire
      electrodes in freely swimming fish. Inactivation of the ophthalmic branch of the
      trigeminal nerve by local anaesthesia revealed its role in the perception of
      intensity/inclination of the magnetic field by abolishing the conditioned
      response (CR). In contrast, experiments with 90 degrees  direction shifts clearly
      showed the normal conditioning effect during trigeminal inactivation. In
      experiments under red light and in darkness, CR occurred in case of both the
      intensity/inclination stimulation and 90 degrees  direction shifts, respectively.
      With regard to the data obtained, we propose the trigeminal system to perceive
      the intensity/inclination of the magnetic field in rainbow trouts and suggest the
      existence of another light-independent sensory structure that enables fish to
      detect the magnetic field direction.

PMID- 22592859
TI  - Individual differences in the Behavioral Inhibition System are associated with
      orbitofrontal cortex and precuneus gray matter volume.
AB  - The Behavioral Inhibition System (BIS) is described in Gray's Reinforcement
      Sensitivity Theory as a hypothetical construct that mediates anxiety in animals
      and humans. The neuroanatomical correlates of this system are not fully clear,
      although they are known to involve the amygdala, the septohippocampal system, and
      the prefrontal cortex. Previous neuroimaging research has related individual
      differences in BIS with regional volume and functional variations in the
      prefrontal cortex, amygdala, and hippocampal formation. The aim of the present
      work was to study BIS-related individual differences and their relationship with
      brain regional volume. BIS sensitivity was assessed through the BIS/BAS
      questionnaire in a sample of male participants (N = 114), and the scores were
      correlated with brain regional volume in a voxel-based morphometry analysis. The
      results show a negative correlation between the BIS and the volume of the right
      and medial orbitofrontal cortices and the precuneus. Our results and previous
      findings suggest that individual differences in anxiety-related personality
      traits and their related psychopathology may be associated with reduced brain
      volume in certain structures relating to emotional control (i.e., the
      orbitofrontal cortex) and self-consciousness (i.e., the precuneus), as shown by
      our results.

PMID- 22592860
TI  - Association of promoter region single nucleotide polymorphisms at positions 
      819C/T and -592C/A of interleukin 10 gene with ischemic heart disease.
AB  - OBJECTIVE: Ischemic heart disease (IHD) is a disease characterized by ischemia of
      the heart muscle, usually due to coronary artery disease. Interleukin-10 (IL10)
      is a proinflammatory cytokine known to protect endothelial function. In this
      study, we investigated the association of promoter region polymorphisms of the
      IL10 gene with IHD. METHODS: We recruited 313 control and 173 IHD patients. The
      selected SNPs in IL10 were genotyped using pyrosequencing. RESULTS: SNPs at
      positions -592C/A and -819C/T were statistically associated with IHD (P = 0.014
      and P = 0.037). Similarly, the mean value of C-reactive protein in the C allele
      at -592C/A and -819C/T was significantly higher than that in the A allele at 
      592C/A (P = 0.026) and T allele at -819C/T (P = 0.026). The presence of
      hypertension in the C allele at -592C/A and -819C/T was significantly more
      frequent than that in the A allele at -592C/A (P = 0.044) and T allele at -819C/T
      (P = 0.044). In the haplotype of two SNPs (-592C/A and -819C/T), one haplotype
      (CC) presented an association with IHD (P = 0.012). CONCLUSIONS: These results
      indicate that the C allele with SNPs at position -592C/A and -819C/T of IL10 gene
      may be associated with IHD in the Korean population.

PMID- 22592861
TI  - Associations between PXK and TYK2 polymorphisms and systemic lupus erythematosus:
      a meta-analysis.
AB  - OBJECTIVE: The aim of this study was to determine whether phox homology domain
      containing serine/threonine kinase (PXK) and tyrosine kinase 2 (TYK2) confer
      susceptibility to systemic lupus erythematosus (SLE). MATERIALS AND METHODS: The
      authors conducted meta-analyses on associations between SLE susceptibility and
      the rs6445975 polymorphism of PXK and the rs2304256, rs12720270, rs280519, and
      rs1272036 polymorphisms of TYK2. RESULTS: A total of 13 separate comparisons
      studies were included in this meta-analysis. Meta-analysis identified an
      association between SLE and the 2 allele of the rs6445975 polymorphism in the
      overall population [odds ratio (OR) = 1.151, 95 % confidence interval (CI) =
      1.086-1.291, P = 1.8E-06]. Stratification by ethnicity identified a significant
      association between this polymorphism and SLE in Europeans (OR = 1.198, 95 % CI =
      1.118-1.285, P = 3.4E-07), but not in Asians. Meta-analysis identified a
      significant negative association between SLE and the 2 allele of the rs2304256
      polymorphism in the overall population (OR = 0.808, 95 % CI = 0.659-0.990, P =
      0.040), and a significant negative association was found in Europeans, but not in
      Asians. CONCLUSIONS: This meta-analysis shows that the rs6445975 polymorphism of
      PXK and the rs2304256 polymorphism of TYK2 are associated with the development of
      SLE in Europeans.

PMID- 22592862
TI  - Sentencing convicted juvenile felony offenders in the adult court: the direct
      effects of race.
AB  - While research indicates that Black and Hispanic adults sentenced in the criminal
      court tend to be rendered more severe punishments than their White counterparts,
      only one prior study has examined whether this finding holds for juveniles tried
      in the adult system. The findings from this sole study need replication, however,
      since the effects posed by trial type were not taken into account and it is
      likely that the results are confounded by measurement error resulting from
      overlap in criminal sentencing. The current study addressed these issues by
      assessing whether race has a direct impact on waived juveniles being criminally
      sentenced to restitution, probation, or jail. Data were derived from a secondary,
      cross-sectional national dataset on felony juvenile offenders convicted in the
      adult system. Three hypotheses were tested. After controlling for a number of
      important legal and extra-legal predictors of sentencing, race differences in
      sentencing outcomes were observed and the findings yielded partial support for
      the hypotheses. The implications of the research are noted.

PMID- 22592863
TI  - Microvascular patterns in the blubber of shallow and deep diving odontocetes.
AB  - Blubber, a specialized form of subdermal adipose tissue, surrounds marine mammal
      bodies. Typically, adipose tissue is perfused by capillaries but information on
      blubber vascularization is lacking. This study's goals were to: 1) describe and
      compare the microvasculature (capillaries, microarterioles, and microvenules) of
      blubber across odontocete species; 2) compare microvasculature of blubber to
      adipose tissue; and 3) examine relationships between blubber's lipid composition
      and its microvasculature. Percent microvascularity, distribution, branching
      pattern, and diameter of microvessels were determined from images of
      histochemically stained blubber sections from shallow-diving bottlenose dolphins
      (Tursiops truncatus), deeper-diving pygmy sperm whales (Kogia breviceps), deep
      diving beaked whales (Mesoplodon densirostris; Ziphius cavirostris), and the
      subdermal adipose tissue of domestic pigs (Sus scrofa). Tursiops blubber showed
      significant stratification in percent microvascularity among the superficial,
      middle, and deep layers and had a significantly higher percent microvascularity
      than all other animals analyzed, in which the microvasculature was more uniformly
      distributed. The percent microvasculature of Kogia blubber was lower than that of
      Tursiops but higher than that of beaked whales and the subdermal adipose tissue
      of domestic pigs. Tursiops had the most microvascular branching. Microvessel
      diameter was relatively uniform in all species. There were no clear patterns
      associating microvascular and lipid characteristics. The microvascular
      characteristics of the superficial layer of blubber resembled the adipose tissue
      of terrestrial mammals, suggesting some conservation of microvascular patterns in
      mammalian adipose tissue. The middle and deep layers of blubber, particularly in
      Tursiops, showed the greatest departure from typical mammalian microvascular
      arrangement. Factors such as metabolics or thermoregulation may be influencing
      the microvasculature in these layers.

PMID- 22592865
TI  - Headache as the sole presentation of cerebral venous thrombosis: a prospective
      study.
AB  - Headache is the most frequent presenting symptom of cerebral venous thrombosis
      (CVT), most commonly associated with other manifestations. It has been described
      as its only clinical presentation in 15 % of patients. There is no typical
      pattern of headache in CVT. The objective of this study was to study the
      characteristics of headache as the sole manifestation of CVT. From a prospective
      study of 30 consecutive patients diagnosed with CVT over 18 months, we selected
      those who presented with headache only: they had a normal neurological
      examination, no papilloedema and no blood or any parenchymal lesion on CT scan.
      All were submitted to a systematic etiological workup and a structured
      questionnaire about the characteristics of headache was provided. Headache was
      the sole manifestation of CVT in 12 patients; it was diffuse or bilateral in the
      majority. Seven patients referred worsening with sleep/lying down, Valsalva
      maneuvers or straining. There was no association between the characteristics of
      headache and extension of CVT. Time from onset to diagnosis was significantly
      delayed in these patients presenting only with headache. In our series, 40 % of
      patients presented only with headache. There was no uniform pattern of headache
      apart from being bilateral. There was a significant delay of diagnosis in these
      patients. Some characteristics of headache should raise the suspicion of CVT:
      recent persistent headache, thunderclap headache or pain worsening with
      straining, sleep/lying down or Valsalva maneuvers even in the absence of
      papilloedema or focal signs.

PMID- 22592864
TI  - Frovatriptan versus almotriptan for acute treatment of menstrual migraine:
      analysis of a double-blind, randomized, cross-over, multicenter, Italian,
      comparative study.
AB  - The objective of the study was to compare the efficacy and safety of frovatriptan
      and almotriptan in women with menstrually related migraine (IHS Classification of
      Headache disorders) enrolled in a multicenter, randomized, double-blind, cross
      over study. Patients received frovatriptan 2.5 mg or almotriptan 12.5 mg in a
      randomized sequence: after treating 3 episodes of migraine in no more than 3
      months with the first treatment, the patient was switched to the other treatment.
      67 of the 96 female patients of the intention-to-treat population of the main
      study had regular menstrual cycles and were thus included in this subgroup
      analysis. 77 migraine attacks classified as related to menses were treated with
      frovatriptan and 78 with almotriptan. Rate of pain relief at 2 and 4 h was 36 and
      53 % for frovatriptan and 41 and 50 % for almotriptan (p = NS between
      treatments). Rate of pain free at 2 and 4 h was 19 and 47 % with frovatriptan and
      29 and 54 % for almotriptan (p = NS). At 24 h, 62 % of frovatriptan-treated and
      67 % of almotriptan-treated patients had pain relief, while 60 versus 67 % were
      pain free (p = NS). Recurrence at 24 h was significantly (p < 0.05) lower with
      frovatriptan (8 vs. 21 % almotriptan). This was the case also at 48 h (9 vs. 24
      %, p < 0.05). Frovatriptan was as effective as almotriptan in the immediate
      treatment of menstrually related migraine attacks. However, it showed a more
      favorable sustained effect, as shown by a lower rate of migraine recurrence.

PMID- 22592870
TI  - Life transitions in the waning of physical activity from childhood to adult life
      in the Trois-Rivieres study.
AB  - BACKGROUND: Several studies have reported an age-related decline of physical
      activity (PA). We examined the impact of 4 important transitional periods
      adolescence, the beginning of postsecondary education, entry into the labor
      market, and parenthood-on the PA of participants in the Trois-Rivieres quasi
      experimental study. METHODS: In 2008, 44 women and 42 men aged 44.0 +/- 1.2 years
      were given a semistructured interview; the frequency and duration of physical
      activities were examined during each of these transition periods. Subjects had
      been assigned to either an experimental program [5 h of weekly physical education
      (PE) from Grades 1 to 6] or the standard curriculum (40 min of weekly PE)
      throughout primary school. RESULTS: The percentage of individuals undertaking >=
      5 h of PA per week decreased from 70.4% to 17.0% between adolescence and midlife.
      The largest decline occurred on entering the labor market (from 55.9% to 23.4%).
      At midlife, there were no significant differences of PA level between
      experimental and control groups. Men were more active than women at each
      transition except for parenthood. CONCLUSIONS: Our results highlight a
      progressive nonlinear decline of PA involvement in both groups. Promotion
      initiatives should target these periods to prevent the decline of PA.

PMID- 22592873
TI  - Sex differences, age, arthritis, and chronic disease: influence on physical
      activity behaviors.
AB  - OBJECTIVE: To examine physical activity (PA) prevalence in individuals with
      arthritis in comparison with those with other chronic diseases. METHODS:
      Descriptive analyses were based on cross-sectional self-reported data for adults
      over age 18 from the Canadian Community Health Survey administered in 2005 (N =
      132,221) for the following groups: arthritis, back problems, other physical
      chronic conditions (ie, diabetes, heart disease, hypertension, and cancer), and
      no physical chronic conditions. RESULTS: The arthritis group did less leisure
      time physical activity than the other 3 groups, they were particularly less
      likely to engage in vigorous physical activities, but were just as likely to walk
      when commuting for errands, work, or school. Older women in the arthritis group
      appeared to be the least active across physical activities and groups.
      CONCLUSIONS: Adults with chronic disease were more physically inactive during
      leisure than those without chronic physical conditions, and older women in the
      arthritis group were particularly limited in our study. A more comprehensive
      assessment of all types of physical activity, including work, leisure, and
      commuting behaviors, need to be done in populations with chronic disease, to
      provide a more accurate portrayal of physical activity participation.

PMID- 22592874
TI  - Cardiorespiratory fitness and carotid artery intima media thickness in men with
      type 2 diabetes.
AB  - BACKGROUND: We tested the hypothesis that higher levels of cardiorespiratory
      fitness are inversely associated with carotid artery intima media thickness in
      746 (age 53 +/- 7 yrs) men with type 2 diabetes. METHODS: We measured common
      carotid intima media thickness and defined carotid atherosclerosis as a carotid
      intima media thickness > 1.0 mm. Cardiorespiratory fitness was directly measured
      by peak oxygen uptake using expired gases analysis during a standard treadmill
      test. RESULTS: Cardiorespiratory fitness was independently associated with common
      carotid intima media thickness in multivariable regression (beta = -0.15, P <
      .05). After adjusting for established risk factors, high and moderate
      cardiorespiratory fitness were associated with lower odds ratios for having
      carotid atherosclerosis--0.49 (95% CI, 0.30-0.81), and 0.59 (95% CI, 0.38-0.92),
      respectively--as compared with low cardiorespiratory fitness. Each 1 metabolic
      equivalent increment higher cardiorespiratory fitness was associated with 27% (OR
      = 0.73; 95% CI, 0.61-0.87) lower prevalence of carotid atherosclerosis.
      CONCLUSIONS: These results suggest that high cardiorespiratory fitness is
      inversely associated with common carotid intima media thickness in men with type
      2 diabetes.

PMID- 22592879
TI  - Cadherin expression delineates the divisions of the postnatal and adult mouse
      amygdala.
AB  - The amygdaloid complex represents a group of telencephalic nuclei and cortical
      areas that control emotional and social behavior. Amygdalar development is poorly
      understood. It is generally accepted that the structures of the amygdala
      originate from the neuroepithelium at both sides of the pallial-subpallial
      boundary. In the present study, we mapped the expression of 13 members of the
      cadherin superfamily of cell adhesion molecules, which provide an adhesive code
      for the development and maintenance of functional structures in the central
      nervous system (CNS). Five classic cadherins (Cdh4, Cdh6, Cdh7, Cdh8, Cdh11) and
      eight delta-protocadherins (Pcdh1, Pcdh7, Pcdh8, Pcdh9, Pcdh10, Pcdh11, PCdh17,
      PCdh19) were studied by in situ hybridization in the postnatal (P5) and adult
      mouse amygdala. In the different parts of the amygdala, each of these (proto-)
      cadherins shows a distinct and spatially restricted expression pattern that is
      highly similar at postnatal and adult stages. The combinatorial expression of
      (proto-) cadherins allows the distinction of multiple molecular subdivisions
      within the amygdala that partially coincide with previously described
      morphological divisions. Beyond these expected results, a number of novel
      molecular subdivisions and subpopulations of cells were identified; for example,
      additional molecular subdomains, patches, or cell aggregates with distinct (proto
      ) cadherin expression in several nuclei/areas of the amygdala. We also show that
      several cadherins are molecular markers for particular functional subsystems
      within the amygdala, such as in the olfactory projections. In summary, (proto-)
      cadherins provide a code of potentially adhesive cues that can aid the
      understanding of functional organization in the amygdala.

PMID- 22592880
TI  - Transitory and activity-dependent expression of neurogranin in olfactory bulb
      tufted cells during mouse postnatal development.
AB  - Neurogranin (Ng) is a brain-specific postsynaptic calmodulin-binding protein
      involved in synaptic activity-dependent plasticity. In the adult olfactory bulb
      (OB), Ng is expressed by a large population of GABAergic interneurons in the
      granule cell layer. We show here that, during postnatal development, Ng is also
      expressed by OB neurons in the superficial external plexiform layer (sEPL) and
      glomerular layer (GL). These Ng-positive neurons display morphological and
      neurochemical features of superficial and external tufted cells. Ng expression in
      these cells is transient during OB development: few elements express Ng at
      postnatal day (P) 5, increasing in number and reaching a peak at P10, then
      progressively decreasing. At P30, Ng is rarely detectable in these neurons. Ng
      expression in developing tufted cells is also modulated at the cellular level: at
      earlier stages, Ng labeling is distributed throughout the cell body and dendritic
      arborization in the GL, but, at P20, when the glomerular circuits are fully
      matured, Ng becomes restricted to the soma and proximal portion of tufted cell
      apical dendrites. We show that olfactory deprivation at early postnatal stages
      induces a strong increase in Ng-positive tufted cells from P10 to P20, whereas no
      changes have been observed following olfactory deprivation in adult mice. These
      findings demonstrate that Ng expression in sEPL-GL is restricted to developmental
      stages and indicate its activity-dependent regulation in a time window critical
      for glomerular circuit development, suggesting a role for Ng in maturation and
      dendritic remodeling of tufted cells.

PMID- 22592881
TI  - Reversing the concept: correction of adolescent idiopathic scoliosis using the
      convex rod de-rotation maneuver.
AB  - PURPOSE: To show the radiological results of adolescent idiopathic scoliosis
      (AIS) patients treated with posterior fusion using all-pedicle-screw construct
      with correction carried out using a convex rod reduction technique. METHODS:
      Between October 2004 and June 2007, 42 AIS patients were treated with posterior
      fusion using all-pedicle-screw construct with correction done through the convex
      side. Two patients were lost to follow-up and were not included in the study.
      Forty patients had a minimum follow-up of 2 years. Patients were evaluated for
      the deformity correction in coronal and sagittal planes and for spinal balance.
      RESULTS: The mean preoperative Cobb angle of the major curve and secondary minor
      curves was 60 degrees  and 41 degrees , respectively. Immediate postoperative
      mean Cobb angle of the major curve and secondary minor curves was 17 degrees  and
      13 degrees , respectively. Postoperative 2-year average major curve loss of
      correction was 7 %. Postoperative 2-year average minor curve loss of correction
      was 5 %. Preoperative thoracic kyphosis of 28 degrees  was changed to 22 degrees 
      in 2-years follow-up. The loss of thoracic kyphosis was most noted in
      hyperkyphotic patients. CONCLUSIONS: The correction of AIS by convex-sided
      pedicular screws yields a coronal correction comparable to what is described in
      the literature for segmental concave-sided screws.

PMID- 22592882
TI  - Cervical range of motion and strength in 4,293 young male adults with chronic
      neck pain.
AB  - PURPOSE: The correlation of cervical biomechanics and neck pain in young patients
      has, to date, only been described in terms of small cohorts. This study focuses
      on the correlation of chronic neck pain and cervical biomechanics. METHODS: Neck
      pain, cervical range of motion (CROM) and maximal cervical torque were recorded
      in 746 patients with conservatively treated chronic neck pain and 3,547
      participants of physiotherapy training without chronic neck pain aged 16-32
      years. RESULTS: The "neck pain" group had a highly significant (s < 0.001) higher
      neck disability index (44.7 vs. 10.4%), longer history of neck pain (3.47 vs.
      0.59 years), higher pain intensity (VAS 5.93 vs. 0.93), higher pain frequency
      (VAS 6.98 vs. 1.09). No differences of CROM and maximal torque in the sagittal,
      frontal and transverse plane were found. CONCLUSION: This study describes the
      largest cohort of biomechanical data of the cervical spine in young adult
      recorded to date. The findings demonstrate that no correlation was found between
      neck pain, CROM and maximal torque in the study cohort. On this basis, we
      conclude that the CROM and maximal cervical torque should not be used as
      indicators to measure the progress of chronic neck pain in physiotherapy training
      and sports medicine for the young adult.

PMID- 22592883
TI  - Risk factors for major peri-operative complications in adult spinal deformity
      surgery: a multi-center review of 953 consecutive patients.
AB  - PURPOSE: Major peri-operative complications for adult spinal deformity (ASD)
      surgery remain common. However, risk factors have not been clearly defined. Our
      objective was to identify patient and surgical parameters that correlate with the
      development of major peri-operative complications with ASD surgery. METHODS: This
      is a multi-center, retrospective, consecutive, case-control series of surgically
      treated ASD patients. All patients undergoing surgical treatment for ASD at eight
      centers were retrospectively reviewed. Each center identified 10 patients with
      major peri-operative complications. Randomization tables were used to select a
      comparably sized control group of patients operated during the same time period
      that they did not suffer major complications. The two groups were analyzed for
      differences in clinical and surgical factors. Analysis was restricted to non
      instrumentation related complications. RESULTS: At least one major complication
      occurred in 80 of 953 patients (8.4 %), including 72 patients with non
      instrumentation related complications. There were no significant differences
      between the complications and control groups based on the demographics, ASA
      grade, co-morbidities, body mass index, prior surgeries, pre-operative anemia,
      smoking, operative time or ICU stay (p > 0.05). Hospital stay was significantly
      longer for the complications group (14.4 vs. 7.9 days, p = 0.001). The
      complications group had higher percentages of staged procedures (46 vs. 37 %, p =
      0.011) and combined anterior-posterior approaches (56 vs. 32 %, p = 0.011)
      compared with the control group. CONCLUSION: The major peri-operative
      complication rate was 8.4 % for 953 surgically treated ASD patients.
      Significantly higher rates of complications were associated with staged and
      combined anterior-posterior surgeries. None of the patient factors assessed were
      significantly associated with the occurrence of major peri-operative
      complications. Improved understanding of risk profiles and procedure-related
      parameters may be useful for patient counseling and efforts to reduce
      complication rates.

PMID- 22592884
TI  - Initiation of radical chain reactions of thiol compounds and alkenes without any
      added initiator: thiol-catalyzed cis/trans isomerization of methyl oleate.
AB  - A kinetic study of the dodecanethiol-catalyzed cis/trans isomerization of methyl
      oleate (cis-2) without added initiator was performed by focusing on the
      initiation of the radical chain reaction. The reaction orders of the rate of
      isomerization were 2 and 0.5 for 1 and cis-2, respectively, and an overall
      kinetic isotope effect k(H)/k(D) of 2.8 was found. The initiation was shown to be
      a complex reaction. The electron-donor/-acceptor (EDA) complex of dodecanethiol
      (1) and cis-2 formed in a pre-equilibrium reacts with thiol 1 to give a stearyl
      and a sulfuranyl radical through molecule-assisted homolysis (MAH) of the sulfur
      hydrogen bond. Fragmentation of the latter gives the thiyl radical, which
      catalyzes the cis/trans isomerization. A computational study of the EDA complex,
      MAH reaction, and the sulfuranyl radical calculated that the activation energy of
      the isomerization was in good agreement with the experimental result of E(A)=82
      kJ  M(-1). Overall, the results may explain that the thermal generation of thiyl
      radicals without any initiator is responsible for many well-known thermally
      initiated addition reactions of thiol compounds to alkenes and their respective
      polymerizations and for the low shelf-life stability of cis-unsaturated thiol
      compounds and of mixtures of alkenes and thiol compounds.

PMID- 22592885
TI  - A philosophical analysis of the general methodology of qualitative research: a
      critical rationalist perspective.
AB  - Philosophical discussion of the general methodology of qualitative research, such
      as that used in some health research, has been inductivist or relativist to date,
      ignoring critical rationalism as a philosophical approach with which to discuss
      the general methodology of qualitative research. This paper presents a discussion
      of the general methodology of qualitative research from a critical rationalist
      perspective (inspired by Popper), using as an example mental health research. The
      widespread endorsement of induction in qualitative research is positivist and is
      suspect, if not false, particularly in relation to the context of justification
      (or rather theory testing) as compared to the context of discovery (or rather
      theory generation). Relativism is riddled with philosophical weaknesses and hence
      it is suspect if not false too. Theory testing is compatible with qualitative
      research, contrary to much writing about and in qualitative research, as theory
      testing involves learning from trial and error, which is part of qualitative
      research, and which may be the form of learning most conducive to generalization.
      Generalization involves comparison, which is a fundamental methodological
      requirement of any type of research (qualitative or other); hence the traditional
      grounding of quantitative and experimental research in generalization. Comparison
      -rather than generalization--is necessary for, and hence compatible with,
      qualitative research; hence, the common opposition to generalization in
      qualitative research is misdirected, disregarding whether this opposition's
      claims are true or false. In conclusion, qualitative research, similar to
      quantitative and experimental research, assumes comparison as a general
      methodological requirement, which is necessary for health research.

PMID- 22592887
TI  - Using donor-specific antibodies to monitor the need for immunosuppression.
AB  - BACKGROUND: Experience with tolerance protocols has shown that none is perfect
      and that each escape from tolerance must be identified early to prevent graft
      failure. In addition, some test is needed for patients who are weaned off
      immunosuppression (IS) to forewarn of weaning failure. The usual measures of
      function--such as serum creatinine levels--are not sensitive enough to detect
      rejection in a timely manner. METHODS: A study was carried out on 72 patients who
      received living-donor kidney transplants with clonal deletion protocol (total
      lymphoid irradiation or bortezomib), and followed with reduced doses of
      maintenance IS. Every month or every 2 months, a test was performed for donor
      specific antibodies (DSA) using Luminex mixed and/or single antigen beads.
      RESULTS: After transplantation, DSA developed in 17% of the patients at 6 months,
      41% at 1 year, and 57% at 2 years, with 95% confidence limits of 10%, 28%; 30%,
      55%; and 44%, 71%, respectively. Fifty-three percent of patients weaned IS to
      less than 10 mg prednisone daily experienced DSA within 3 months. Furthermore,
      prednisone dose (per 2.5 mg) and years after transplantation were inversely
      associated with DSA production (risk ratio 0.92 [95% confidence limits: 0.85,
      0.99], and 0.70 [0.49, 1.00]). CONCLUSIONS: DSA monitoring is highly effective
      for detecting escape from tolerance and reemergence of the immune response in
      weaned patients. DSA appearance was inversely proportional to the level of
      maintenance drugs in the weaning process. Measurement of DSA on a monthly basis
      is adequate for detection of the change in immune reactivity.

PMID- 22592888
TI  - Vascularized composite allotransplantation:  a member of the transplant family?
AB  - The definition of vascularized composite allograft (VCA) and the nomenclature
      require further attention and interaction with the competent authorities. When
      compared with solid organ transplantation, VCA donation and allocation imply
      additional elements such as donor identification, race, and bone constitution,
      which need to be worked into a scheme for VCA allocation. Furthermore, retrieval
      of limbs, faces, and possibly other body parts demands algorithms for the
      sequence of steps during the donor operation. Relevant aspects and criteria for
      any VCA allocation concept are addressed in this article.

PMID- 22592886
TI  - Discovery and validation of a molecular signature for the noninvasive diagnosis
      of human renal allograft fibrosis.
AB  - BACKGROUND: Tubulointerstitial fibrosis (fibrosis), a histologic feature
      associated with a failing kidney allograft, is diagnosed using the invasive
      allograft biopsy. A noninvasive diagnostic test for fibrosis may help improve
      allograft outcome. METHODS: We obtained 114 urine specimens from 114 renal
      allograft recipients: 48 from 48 recipients with fibrosis in their biopsy results
      and 66 from 66 recipients with normal biopsy results. Levels of messenger RNAs
      (mRNAs) in urinary cells were measured using kinetic, quantitative polymerase
      chain reaction assays, and the levels were related to allograft diagnosis. A
      discovery set of 76 recipients (32 with allograft fibrosis and 44 with normal
      biopsy results) was used to develop a diagnostic signature, and an independent
      validation set of 38 recipients (16 with allograft fibrosis and 22 with normal
      biopsy results) was used to validate the signature. RESULTS: In the discovery
      set, urinary cell levels of the following mRNAs were significantly associated
      with the presence of allograft fibrosis: vimentin (P<0.0001, logistic regression
      model), hepatocyte growth factor (P<0.0001), alpha-smooth muscle actin
      (P<0.0001), fibronectin 1 (P<0.0001), perforin (P=0.0002), plasminogen activator
      inhibitor 1 (P=0.0002), transforming growth factor beta1 (P=0.0004), tissue
      inhibitor of metalloproteinase 1 (P=0.0009), granzyme B (P=0.0009), fibroblast
      specific protein 1 (P=0.006), CD103 (P=0.02), and collagen 1A1 (P=0.04). A four
      gene model composed of the levels of mRNA for vimentin, NKCC2, and E-cadherin and
      of 18S ribosomal RNA provided the most accurate, parsimonious diagnostic model of
      allograft fibrosis with a sensitivity of 93.8% and a specificity of 84.1%
      (P<0.0001). In the independent validation set, this same model predicted the
      presence of allograft fibrosis with a sensitivity of 77.3% and a specificity of
      87.5% (P<0.0001). CONCLUSIONS: Measurement of mRNAs in urinary cells may offer a
      noninvasive means of diagnosing fibrosis in human renal allografts.

PMID- 22592889
TI  - One-step sonochemical synthesis of a graphene oxide-manganese oxide nanocomposite
      for catalytic glycolysis of poly(ethylene terephthalate).
AB  - Ultrasound-assisted synthesis of a graphene oxide (GO)-manganese oxide
      nanocomposite (GO-Mn(3)O(4)) was conducted without further modification of GO or
      employing secondary materials. With the GO nanoplate as a support, potassium
      permanganate oxidizes the carbon atoms in the GO support and gets reduced to
      Mn(3)O(4). An intensive ultrasound method could reduce the number of reaction
      steps and temperature, enhance the reaction rate and furthermore achieve a
      Mn(3)O(4) phase. The composite was characterized by X-ray diffraction (XRD), X
      ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM),
      scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). The
      coverage and crystallinity of Mn(3)O(4) were controlled by changing the ratio of
      permanganate to GO dispersion. The synthesized nanocomposite was used as a
      catalyst for poly(ethylene terephthalate) (PET) depolymerization into its
      monomer, bis(2-hydroxylethyl) terephthalate (BHET). The highest monomer yield of
      96.4% was obtained with the nanocomposite containing the lowest amount of
      Mn(3)O(4), while PET glycolysis with the Mn(3)O(4) without GO yielded 82.7% BHET.

PMID- 22592890
TI  - Hair cortisol: a parameter of chronic stress? Insights from a radiometabolism
      study in guinea pigs.
AB  - Measurement of hair cortisol has become popular in the evaluation of chronic
      stress in various species. However, a sound validation is still missing.
      Therefore, deposition of radioactivity in hair and excretion into feces and urine
      after repeated injection of (3)H-cortisol was studied in guinea pigs (n = 8).
      Each animal was given intraperitoneally 243.6 kBq (3)H-cortisol/day on 3
      successive days. After the first injection, all voided excreta were collected for
      3 days. After the second injection, hair was shaved off the animals' back and
      newly grown hair was obtained on day 7. Following methanol extraction,
      radiolabeled and unlabeled glucocorticoid metabolites (GCM) in fecal and hair
      samples were characterized by high-performance liquid chromatography (HPLC) and
      enzyme immunoassays (EIA). In feces, maximum radioactivity was reached 8 h
      (median) post each injection, whereas maxima in urine were detected in the first
      samples (median 2.5 h). Metabolites excreted into feces (13.3% +/- 3.7) or urine
      (86.7%) returned nearly to background levels. HPLC of fecal extracts showed minor
      variation between individuals and sexes. In hair, small amounts of radioactivity
      were present. However, two EIAs detected large amounts of unlabeled GCM,
      including high levels at the position of the cortisol standard; radioactivity was
      absent in this fraction, demonstrating that (3)H-cortisol was metabolized.
      Furthermore, large amounts of immunoreactivity coinciding with a radioactive peak
      at the elution position of cortisone were found. These results show for the first
      time that only small amounts of systemically administered radioactive
      glucocorticoids are deposited in hair of guinea pigs, while measurement of large
      amounts of unlabeled GCM strongly suggests local production of glucocorticoids in
      hair follicles.

PMID- 22592892
TI  - First MU-CT-based 3D reconstruction of a dipteran larva-the head morphology of
      Protanyderus (Tanyderidae) and its phylogenetic implications.
AB  - The larval head of Protanyderus was examined and documented using innovative
      techniques, with emphasis on internal structures. A chart listing all head
      muscles of dipteran larvae and other holometabolan groups is presented in the
      Supporting Information. The results are compared to conditions found in other
      nematoceran lineages. The larval head of Protanyderus is characterized mainly by
      plesiomorphic character states such as the complete and largely exposed head
      capsule, the long coronal suture, V-shaped frontal sutures, lateral antennal
      insertion areas, a transverse labrum, a nearly horizontal plane of mandibular
      movements, mandibles lacking a movable distal part, a mesal hook and mesal or
      distal combs, separated maxillary endite lobes, a comparatively complete array of
      muscles, and a brain only partly located within the head capsule. An anteriorly
      toothed hypostomal plate and dense labral brushes of microtrichiae are also
      likely groundplan features of Diptera. The pharyngeal filter is a possible
      apomorphy of Diptera excl. Deuterophlebiidae (or Deuterophlebiidae +
      Nymphomyiidae). The messors have also likely evolved early in the dipteran crown
      group but are absent in the groundplan. The phylogenetic interpretation of
      externolateral plates with growth lines is ambiguous. Autapomorphies of
      Tanyderidae are differences between the third and fourth instar larvae, the roof
      like extension above the antennal insertion area, the dorsal endocarina, and the
      posterodorsal internal ridge. The phylogenetic position of Tanyderidae is
      controversial, but features of the larval head do not support a proposed
      sistergroup relationship between Tanyderidae and Psychodidae. Both groups differ
      in many features of the larval head, and we did not identify a single potential
      synapomorphy. Larval characters alone are insufficient for a reliable
      phylogenetic reconstruction, though they vary greatly and apparently contain
      phylogenetic information. The evaluation of these features in the context of
      robust molecular phylogenies will be a sound basis for the reconstruction of
      complex evolutionary scenarios for the megadiverse Diptera.

PMID- 22592891
TI  - Long-term administration of AMD3100, an antagonist of SDF-1/CXCR4 signaling,
      alters fracture repair.
AB  - Fracture healing involves rapid stem and progenitor cell migration, homing, and
      differentiation. SDF-1 (CXCL12) is considered a master regulator of CXCR4
      positive stem and progenitor cell trafficking to sites of ischemic (hypoxic)
      injury and regulates their subsequent differentiation into mature reparative
      cells. In this study, we investigated the role of SDF-1/CXCR4 signaling in
      fracture healing where vascular disruption results in hypoxia and SDF-1
      expression. Mice were injected with AMD3100, a CXCR4 antagonist, or vehicle twice
      daily until euthanasia with the intent to impair stem cell homing to the fracture
      site and/or their differentiation. Fracture healing was evaluated using micro
      computed tomography, histology, quantitative PCR, and mechanical testing. AMD3100
      administration resulted in a significantly reduced hyaline cartilage volume (day
      14), callus volume (day 42) and mineralized bone volume (day 42) and reduced
      expression of genes associated with endochondral ossification including collagen
      Type 1 alpha 1, collagen Type 2 alpha 1, vascular endothelial growth factor,
      Annexin A5, nitric oxide synthase 2, and mechanistic target of rapamycin. Our
      data suggest that the SDF-1/CXCR4 signaling plays a central role in bone healing
      possibly by regulating the recruitment and/or differentiation of stem and
      progenitor cells.

PMID- 22592893
TI  - A ternary model for double-emulsion formation in a capillary microfluidic device.
AB  - To predict double-emulsion formation in a capillary microfluidic device, a
      ternary diffuse-interface model is presented. The formation of double emulsions
      involves complex interfacial phenomena of a three-phase fluid system, where each
      component can have different physical properties. We use the Navier-Stokes/Cahn
      Hilliard model for a general ternary system, where the hydrodynamics is coupled
      with the thermodynamics of the phase field variables. Our model predicts
      important features of the double-emulsion formation which was observed
      experimentally by Utada et al. [Utada et al., Science, 2005, 308, 537]. In
      particular, our model predicts both the dripping and jetting regimes as well as
      the transition between those two regimes by changing the flow rate conditions. We
      also demonstrate that a double emulsion having multiple inner drops can be formed
      when the outer interface is more stable than the inner interface.

PMID- 22592894
TI  - Septohippocampal GABAergic neurons mediate the altered behaviors induced by n
      methyl-D-aspartate receptor antagonists.
AB  - We hypothesize that selective lesion of the septohippocampal GABAergic neurons
      suppresses the altered behaviors induced by an N-methyl-D-aspartate (NMDA)
      receptor antagonist, ketamine or MK-801. In addition, we hypothesize that
      septohippocampal GABAergic neurons generate an atropine-resistant theta rhythm
      that coexists with an atropine-sensitive theta rhythm in the hippocampus.
      Infusion of orexin-saporin (ore-SAP) into the medial septal area decreased
      parvalbumin-immunoreactive (GABAergic) neurons by ~80%, without significantly
      affecting choline-acetyltransferase-immunoreactive (cholinergic) neurons. The
      theta rhythm during walking, or the immobility-associated theta induced by
      pilocarpine, was not different between ore-SAP and sham-lesion rats. Walking
      theta was, however, more disrupted by atropine sulfate in ore-SAP than in sham
      lesion rats. MK-801 (0.5 mg/kg i.p.) induced hyperlocomotion associated with an
      increase in frequency, but not power, of the hippocampal theta in both ore-SAP
      and sham-lesion rats. However, MK-801 induced an increase in 71-100 Hz gamma
      waves in sham-lesion but not ore-SAP lesion rats. In sham-lesion rats, MK-801
      induced an increase in locomotion and an impairment of prepulse inhibition (PPI),
      and ketamine (3 mg/kg s.c.) induced a loss of gating of hippocampal auditory
      evoked potentials. MK-801-induced behavioral hyperlocomotion and PPI impairment,
      and ketamine-induced auditory gating deficit were reduced in ore-SAP rats as
      compared to sham-lesion rats. During baseline without drugs, locomotion and
      auditory gating were not different between ore-SAP and sham-lesion rats, and PPI
      was slightly but significantly increased in ore-SAP as compared with sham lesion
      rats. It is concluded that septohippocampal GABAergic neurons are important for
      the expression of hyperactive and psychotic symptoms an enhanced hippocampal
      gamma activity induced by ketamine and MK-801, and for generating an atropine
      resistant theta. Selective suppression of septohippocampal GABAergic activity is
      suggested to be an effective treatment of some symptoms of schizophrenia.

PMID- 22592895
TI  - The effects of emotion and encoding strategy on associative memory.
AB  - Research has demonstrated that when discrete pieces of information are integrated
      together at encoding--imagining two items together as a single entity, for
      example--there is a mnemonic benefit for their relationship. A separate body of
      literature has indicated that the presence of emotional information can have an
      impact on the binding of associated neutral details, in some cases facilitating
      associative binding (MacKay et al. Memory and cognition 32:474-488, 2004; Mather,
      perspectives on psychological science 2:33-52, 2007), and in other cases impeding
      the processing of associated details (Easterbrook, Psychological Review 66:183
      201, 1959; Kensinger, Emotion review 1:99-113, 2009). In the present experiments,
      we investigated how memory for neutral words is affected by the emotionality of
      the information with which they are presented (whether with an emotional word or
      a second neutral word) and the encoding context (integrated or nonintegrated
      strategy). Participants viewed word pairs and were instructed to visualize the
      items as an integrated unit or to visualize them separately from one another. The
      results of Experiment 1 showed a disproportionate mnemonic benefit for neutral
      items that were integrated with other neutral items over those integrated with
      emotional items. The results of Experiments 2A and 2B showed that this effect
      interacted with encoding time: When given 2 s to encode, participants showed no
      effect of integration on memory for neutral-neutral pairs, but showed a
      significant mnemonic benefit for integrating emotional-neutral pairs. When given
      4 or 6 s, the integrative benefit increased significantly for neutral-neutral
      pairs but decreased for emotional-neutral pairs. These results suggest that
      creating an integrated mental image of two neutral items requires a more time
      consuming process than integrating an emotional and a neutral item, but that
      extra effort may result in a downstream mnemonic benefit.

PMID- 22592896
TI  - Persistent renal damage after contrast-induced acute kidney injury: incidence,
      evolution, risk factors, and prognosis.
AB  - BACKGROUND: The temporal evolution of renal function in patients with acute
      kidney injury after contrast medium (CI-AKI) is not well known. The aim of this
      observational study was to evaluate the incidence, risk factors, and prognostic
      implications of persistent renal damage (RD) in patients with preexistent
      moderate-to-severe renal dysfunction. METHODS AND RESULTS: From June 2003 to
      March 2008, 3986 patients underwent coronary angiography at our institution; 1490
      of 3986 had an estimated creatinine clearance of <60 mL/min and were enrolled. CI
      AKI was defined as an absolute increase >= 0.5 mg/dL over baseline serum
      creatinine within 3 days after the administration of contrast medium (iodixanol).
      In patients who developed CI-AKI, persistent RD was defined as a relative
      decrease of creatinine clearance >= 25% over baseline at 3 months. Patients whose
      creatinine clearance returned to baseline (or nearly) were classified as
      transient RD. The overall incidence of CI-AKI was 12.1%, and persistent RD
      occurred in 18.6% of CI-AKI patients. At Cox regression analysis, nephropathy
      risk score >= 17, left ventricular ejection fraction <= 30%, and increased value
      of serum creatinine >= 1.5-fold from baseline within 5 days were found to be
      significant risk factors for persistent RD. At 5 years, the incidence of death
      was significantly higher in patients with persistent RD than in both patients
      with transient RD (P=0.015) and those without CI-AKI (P=0.0001). A similar trend
      was observed for the combined end point of death, dialysis and cardiovascular
      events. CONCLUSIONS: These results suggest that CI-AKI is not always a transient,
      benign creatininopathy, but rather a direct cause of worsening renal function.
      The occurrence of CI-AKI can identify patients at increased risk of
      cardiovascular events.

PMID- 22592897
TI  - Impaired autophagosome clearance contributes to cardiomyocyte death in
      ischemia/reperfusion injury.
AB  - BACKGROUND: In myocardial ischemia, induction of autophagy via the AMP-induced
      protein kinase pathway is protective, whereas reperfusion stimulates autophagy
      with BECLIN-1 upregulation and is implicated in causing cell death. We examined
      flux through the macroautophagy pathway as a determinant of the discrepant
      outcomes in cardiomyocyte cell death in this setting. METHODS AND RESULTS:
      Reversible left anterior descending coronary artery ligation was performed in
      mice with cardiomyocyte-restricted expression of green fluorescent protein-tagged
      microtubule-associated protein light chain-3 to induce ischemia (120 minutes) or
      ischemia/reperfusion (30-90 minutes) with saline or chloroquine pretreatment (n=4
      per group). Autophagosome clearance, assessed as the ratio of punctate light
      chain-3 abundance in saline to chloroquine-treated samples, was markedly impaired
      with ischemia/reperfusion compared with sham controls. Reoxygenation increased
      cell death in neonatal rat cardiomyocytes compared with hypoxia alone, markedly
      increased autophagosomes but not autolysosomes (assessed as punctate dual
      fluorescent mCherry-green fluorescent protein tandem-tagged light chain-3
      expression), and impaired clearance of polyglutamine aggregates, indicating
      impaired autophagic flux. The resultant autophagosome accumulation was associated
      with increased reactive oxygen species and mitochondrial permeabilization,
      leading to cell death, which was attenuated by cyclosporine A pretreatment.
      Hypoxia-reoxygenation injury was accompanied by reactive oxygen species-mediated
      BECLIN-1 upregulation and a reduction in lysosome-associated membrane protein-2,
      a critical determinant of autophagosome-lysosome fusion. Restoration of lysosome
      associated membrane protein-2 levels synergizes with partial BECLIN-1 knockdown
      to restore autophagosome processing and to attenuate cell death after hypoxia
      reoxygenation. CONCLUSION: Ischemia/reperfusion injury impairs autophagosome
      clearance mediated in part by reactive oxygen species-induced decline in lysosome
      associated membrane protein-2 and upregulation of BECLIN-1, contributing to
      increased cardiomyocyte death.

PMID- 22592898
TI  - Reduced endoglin activity limits cardiac fibrosis and improves survival in heart
      failure.
AB  - BACKGROUND: Heart failure is a major cause of morbidity and mortality worldwide.
      The ubiquitously expressed cytokine transforming growth factor-beta1 (TGFbeta1)
      promotes cardiac fibrosis, an important component of progressive heart failure.
      Membrane-associated endoglin is a coreceptor for TGFbeta1 signaling and has been
      studied in vascular remodeling and preeclampsia. We hypothesized that reduced
      endoglin expression may limit cardiac fibrosis in heart failure. METHODS AND
      RESULTS: We first report that endoglin expression is increased in the left
      ventricle of human subjects with heart failure and determined that endoglin is
      required for TGFbeta1 signaling in human cardiac fibroblasts using neutralizing
      antibodies and an siRNA approach. We further identified that reduced endoglin
      expression attenuates cardiac fibrosis, preserves left ventricular function, and
      improves survival in a mouse model of pressure-overload-induced heart failure.
      Prior studies have shown that the extracellular domain of endoglin can be cleaved
      and released into the circulation as soluble endoglin, which disrupts TGFbeta1
      signaling in endothelium. We now demonstrate that soluble endoglin limits
      TGFbeta1 signaling and type I collagen synthesis in cardiac fibroblasts and
      further show that soluble endoglin treatment attenuates cardiac fibrosis in an in
      vivo model of heart failure. CONCLUSION: Our results identify endoglin as a
      critical component of TGFbeta1 signaling in the cardiac fibroblast and show that
      targeting endoglin attenuates cardiac fibrosis, thereby providing a potentially
      novel therapeutic approach for individuals with heart failure.

PMID- 22592899
TI  - Targeting endoglin, an auxiliary transforming growth factor beta coreceptor, to
      prevent fibrosis and heart failure.

PMID- 22592900
TI  - Off-Pump coronary artery bypass surgery is associated with worse arterial and
      saphenous vein graft patency and less effective revascularization: Results from
      the Veterans Affairs Randomized On/Off Bypass (ROOBY) trial.
AB  - BACKGROUND: The Department of Veterans Affairs Randomized On/Off Bypass (ROOBY)
      trial compared clinical and angiographic outcomes in off-pump versus on-pump
      coronary artery bypass graft (CABG) surgery to ascertain the relative efficacy of
      the 2 techniques. METHODS AND RESULTS: From February 2002 to May 2007, the ROOBY
      trial randomized 2203 patients to off-pump versus on-pump CABG. Follow-up
      angiography was obtained in 685 off-pump (62%) and 685 on-pump (62%) patients.
      Angiograms were analyzed (blinded to treatment) for FitzGibbon classification
      (A=widely patent, B=flow limited, O=occluded) and effective revascularization.
      Effective revascularization was defined as follows: All 3 major coronary
      territories with significant disease were revascularized by a FitzGibbon A
      quality graft to the major diseased artery, and there were no new postanastomotic
      lesions. Off-pump CABG resulted in lower FitzGibbon A patency rates than on-pump
      CABG for arterial conduits (85.8% versus 91.4%; P=0.003) and saphenous vein
      grafts (72.7% versus 80.4%; P<0.001). Fewer off-pump patients were effectively
      revascularized (50.1% versus 63.9% on-pump; P<0.001). Within each major coronary
      territory, effective revascularization was worse off pump than on pump (all
      P<=0.001). The 1-year adverse cardiac event rate was 16.4% in patients with
      ineffective revascularization versus 5.9% in patients with effective
      revascularization (P<0.001). CONCLUSIONS: Off-pump CABG resulted in significantly
      lower FitzGibbon A patency for arterial and saphenous vein graft conduits and
      less effective revascularization than on-pump CABG. At 1 year, patients with less
      effective revascularization had higher adverse event rates. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00032630.

PMID- 22592901
TI  - Graft patency after off-pump coronary artery bypass surgery.

PMID- 22592902
TI  - Sex differences in escalation of methamphetamine self-administration: cognitive
      and motivational consequences in rats.
AB  - RATIONALE: Male rats escalate methamphetamine (meth) intake during long-access
      meth self-administration, show enhanced reinstatement of meth-seeking, and
      exhibit meth-induced memory impairments. However, the impact of long-access daily
      meth self-administration on reinstatement and cognitive dysfunction has not been
      assessed in females, even though clinical studies on meth addiction have shown
      differences between men and women. OBJECTIVES: This study determined whether male
      and freely cycling female rats: (1) escalate meth intake in a 6-h daily-access
      period relative to 1-h access; (2) show different sensitivity to meth primed
      reinstatement after short- and long-access conditions; and (3) show deficits in
      novel object and object in place recognition memory. METHODS: Male and female
      Long-Evans rats self-administered meth in limited (1-h/day) or extended (6-h/day)
      daily access sessions. After 21 days, meth access was discontinued, and rats
      entered an abstinence period. On the seventh and 14th days of abstinence, rats
      were assessed for recognition memory using tests for: (a) novel object
      recognition memory and (b) object-in-place memory. Rats were tested for
      reinstatement of meth-seeking following extinction of responding. RESULTS: Female
      rats self-administered more meth and escalated intake faster than males during
      extended, but not limited, daily access. Both males and females in the extended,
      but not limited, access groups showed memory deficits on both tasks. Female rats
      showed greater reinstatement to meth-seeking with lower doses of meth priming
      injections than males. CONCLUSIONS: Relative to males, females were equally
      susceptible to meth-induced memory deficits but exhibited higher meth intake and
      greater relapse to meth-seeking.

PMID- 22592904
TI  - Information commissioner condemns health secretary for failing to publish risk
      register.

PMID- 22592903
TI  - The brain orexin system and almorexant in fear-conditioned startle reactions in
      the rat.
AB  - RATIONALE: The rat fear-potentiated startle (FPS) paradigm is a translational
      model of conditioned fear involving central amygdala pathways of the brain.
      Hypothalamic orexin neurons have input-output projections to the amygdala; they
      modulate vigilance and stress-related responses. OBJECTIVE: To investigate
      whether the transient pharmacological blockade of orexin receptors moderates the
      conditioned fear response. METHODS: F344 rats received acute oral treatment with
      the dual orexin receptor antagonist almorexant (30-300 mg/kg) or with one of the
      clinically effective anxiolytics diazepam (1-10 mg/kg), buspirone (10-100 mg/kg),
      fluoxetine (3-30 mg/kg), and sertraline (10-100 mg/kg). Drug effects on startle
      responses were assessed in both fear- and non-fear-conditioned rats; on forepaw
      grip and horizontal wire motor performance, and on elevated plus maze (EPM)
      behavior. RESULTS: Diazepam and almorexant both dose-dependently decreased FPS in
      the presence of the fear-conditioned stimulus (CS; light) more prominently than
      background startle in absence of the CS (dark). Diazepam induced myorelaxation
      and reduced startle responses in control non-fear-conditioned rats. Almorexant
      had no myorelaxant effects and left startle responses under light in non-fear
      conditioned rats intact. On the EPM, diazepam showed anxiolytic-like effects,
      almorexant not. Buspirone demonstrated anxiolytic-like effects on FPS by
      simultaneously reducing CS-related startle and increasing no-CS-background
      startle. Fluoxetine did not affect FPS, whereas sertraline showed anxiogenic-like
      effects. CONCLUSIONS: Almorexant reduced FPS, but did not affect EPM behavior.
      Almorexant's overall pattern of effects on FPS was comparable to but less
      pronounced than that of the anxiolytic benzodiazepine diazepam. The endogenous
      orexin system actively contributes to fear-conditioned startle reactions in the
      rat.

PMID- 22592905
TI  - US citizens are less healthy but living longer, report says.

PMID- 22592906
TI  - A complex chromosomal rearrangement involving chromosomes 2, 5, and X in autism
      spectrum disorder.
AB  - Here, we describe a female patient with autism spectrum disorder and dysmorphic
      features that harbors a complex genetic alteration, involving a de novo balanced
      translocation t(2;X)(q11;q24), a 5q11 segmental trisomy and a maternally
      inherited isodisomy on chromosome 5. All the possibly damaging genetic effects of
      such alterations are discussed. In light of recent findings on ASD genetic
      causes, the hypothesis that all these alterations might be acting in
      orchestration and contributing to the phenotype is also considered.

PMID- 22592907
TI  - Air pollution interventions and their impact on public health.
AB  - INTRODUCTION: Numerous epidemiological studies have found a link between air
      pollution and health. We are reviewing a collection of published intervention
      studies with particular focus on studies assessing both improvements in air
      quality and associated health effects. METHODS: Interventions, defined as events
      aimed at reducing air pollution or where reductions occurred as a side effect,
      e.g. strikes, German reunification, from the 1960s onwards were considered for
      inclusion. This review is not a complete record of all existing air pollution
      interventions. In total, 28 studies published in English were selected based on a
      systematic search of internet databases. RESULTS: Overall air pollution
      interventions have succeeded at improving air quality. Consistently published
      evidence suggests that most of these interventions have been associated with
      health benefits, mainly by the way of reduced cardiovascular and/or respiratory
      mortality and/or morbidity. The decrease in mortality from the majority of the
      reviewed interventions has been estimated to exceed the expected predicted
      figures based on the estimates from time-series studies. CONCLUSION: There is
      consistent evidence that decreased air pollution levels following an intervention
      resulted in health benefits for the assessed population.

PMID- 22592908
TI  - Mesenteric fibromatosis of the transverse colon with the reconstruction of the
      superior mesenteric arteries: report of a case.
AB  - In general, with large mesenteric tumors it may be rather difficult to determine
      whether infiltration into adjacent large vessels occurred. We wish to stress the
      importance of preparation for microsurgery when a huge lesion appears close to a
      large artery in preoperative images, based on our experience of successful
      microscopical reconstruction of a superior mesenteric artery (SMA) and marked
      improvement of blocked vascular flow to the small intestine during the surgery.
      We have experienced a case of mesenteric fibromatosis (MF) invading the SMA and
      vein, contrary to preoperative expectation. The patient underwent extirpation of
      a MF, 21 cm in size, with reconstruction of the SMA by microsurgery. The
      sacrificed small intestine was only 80 cm of the distal ileum with the benefit of
      microscopic anastomosis between the SMA and a major jejunal artery. Preparations
      for microscopic surgery must be made with resection of large lesions, because
      involvement of mesenteric large vessels may be expected. It is possible for
      microsurgery to extend indications for surgical resection of huge mesenteric
      tumors.

PMID- 22592909
TI  - Quercetin inhibits IL-1beta-induced proliferation and production of MMPs, COX-2,
      and PGE2 by rheumatoid synovial fibroblast.
AB  - This study was aimed to determine the effects of quercetin on the interleukin
      1beta (IL-1beta)-induced proliferation of rheumatoid synovial fibroblasts (RASFs)
      and production of matrix metalloproteinases (MMPs), cyclooxygenase (COX), and
      prostaglandin E2 (PGE2) by RASFs. The proliferation and apoptosis of RASFs was
      evaluated with CCK-8 reagent and flow cytometry in the presence of IL-1with CCK-8
      reagquercetin. The expression of MMPs, IL-1beta enhanced the expression of MMP-1,
      MMP-3, tissue inhibitor of metalloproteinase (TIMP)-1, COXs, PGE2, and
      intracellular mitogen-activated protein kinase (MAPK) signalings including
      phosphorylated extracellular signal-regulated kinase (p-ERK), p-p38,
      phosphorylated c-Jun N-terminal kinase (p-JNK), and nuclear factor kB (NF-kB)
      were examined by immunoblotting or semiquantitative reverse transcription
      polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA)
      in conditions as described above. Quercetin inhibits unstimulated and IL-1beta
      induced proliferation of RASFs and MMP-1, 3, COX-2 messenger ribonucleic acid and
      protein expression, PGE2 production induced with IL-1beta. Quercetin also
      inhibits the phosphorylation of ERK-1/2, p38, JNK and activation of NF-kB by IL
      1ed. These results indicate that quercetin inhibits synovial fibroblasts
      proliferation and MMPs, COX-2, and PGE2 production, which involved joint
      destruction in rheumatoid arthritis (RA), and suggest that it might be a new
      therapeutic agent for management of RA.

PMID- 22592910
TI  - Detection of occurrence of a recent genetic bottleneck event in Indian hill
      cattle breed Bargur using microsatellite markers.
AB  - The effective number of breedable individuals is a crucial determinant for
      maintaining genetic variability within a population. The population of Bargur,
      the hill cattle of South India, has gone down drastically by more than 93 % in
      the past three decades, and only a few thousand animals are available at present.
      The present study was undertaken to evaluate Bargur cattle for mutation drift
      equilibrium and to detect the occurrence of recent genetic bottleneck event, if
      any, in this population. About 50 unrelated animals, true to the type, were
      sampled and genotyped at 25 microsatellite loci. The mean observed heterozygosity
      (0.808 +/- 0.023) was higher than the mean expected heterozygosity (0.762 +/-
      0.008) with 15 out of 25 microsatellite loci exhibiting heterozygosity excess
      when assumed under Hardy-Weinberg equilibrium. To evaluate Bargur cattle for
      mutation drift equilibrium, three tests were performed under three different
      mutation models, viz., infinite allele model (IAM), stepwise mutation model (SMM)
      and two-phase model (TPM). The observed gene diversity (H (e)) and expected
      equilibrium gene diversity (H(eq)) were estimated under different models of
      microsatellite evolution. All the 25 loci were found to exhibit gene diversity
      excess under IAM and TPM, while 22 loci were having gene diversity excess under
      SMM. All the three statistical tests, viz., sign test, standardized differences
      test, and Wilcoxon sign rank test, revealed significant (P < 0.01) deviation of
      Bargur cattle population from mutation-drift equilibrium under all the three
      models of mutation. Furthermore, the qualitative test of allele frequency
      distribution in Bargur cattle population revealed a strong mode shift from the
      normal L-shaped form suggesting that the population had experienced genetic
      bottleneck in the recent past. The occurrence of genetic bottleneck might have
      led to the loss of several rare alleles in the population, which point towards
      the need for efforts to conserve this important cattle germplasm. The present
      study is the first report in demonstrating the genetic basis of demographic
      bottleneck in an Indian cattle population.

PMID- 22592911
TI  - Famotidine suppresses osteogenic differentiation of tendon cells in vitro and
      pathological calcification of tendon in vivo.
AB  - Heterotopic ossification or calcification follows any type of musculoskeletal
      trauma and is known to occur after arthroplasties of hip, knee, shoulder, or
      elbow; fractures; joint dislocations; or tendon ruptures. Histamine receptor H2
      (Hrh2) has been shown to be effective for reducing pain and decreasing
      calcification in patients with calcifying tendinitis, which suggested that H2
      blockers were effective for the treatment of tendon ossification or
      calcification. However, the detailed mechanisms of its action on tendon remain to
      be clarified. We investigated the mechanisms underlying H2 blocker-mediated
      suppression of tendon calcification, with a focus on the direct action of the
      drug on tendon cells. Famotidine treatment suppressed the mRNA expressions of
      Col10a1 and osteocalcin, ossification markers, in a tendon-derived cell line TT
      D6, as well as a preosteoblastic one MC3T3-E1. Both of the cell lines expressed
      Hrh2; histamine treatment induced osteocalcin expression in these cells.
      Famotidine administration suppressed calcification in the Achilles tendon of ttw
      mice, a mouse model of ectopic ossification. These data suggest that famotidine
      inhibits osteogenic differentiation of tendon cells in vitro, and this inhibition
      may underlie the anti-calcification effects of the drug in vivo. This study
      points to the use of H2 blockers as a promising strategy for treating heterotopic
      ossification or calcification in tendon, and provides evidence in support of the
      clinical use of famotidine.

PMID- 22592912
TI  - Enantio- and chemoselective differentiation of protected alpha-amino acids and
      beta-homoamino acids with a single copper(II) host.
AB  - The association between an achiral copper(II)-containing host 1 and chiral
      carboxylates has been expanded beyond previous studies to new chiral carboxylate
      guests, both alpha-amino acids and beta-homoamino acids. The observed exciton
      coupled circular dichroism (ECCD) signals for the enantiomers of each carboxylate
      were equal and opposite, and these signals differed in size and shape between the
      individual amino acids. Linear discriminant analysis (LDA) was applied as a
      statistical analysis technique to differentiate the amino acids, both
      enantioselectively and chemoselectively, giving the absolute configuration and
      identity of the amino acid. The identity of each of the alpha-amino acids and
      beta-homoamino acids were determined independently by LDA, and then the two were
      considered together. Each of these analyses showed good differentiation of the
      amino acid guests with the use of only one host molecule.

PMID- 22592913
TI  - Beneficial effects following microsurgical decompression in an adult with
      congenital thoraco-lumbar kyphoscoliosis with spina bifida aperta and
      myelomeningocele: an interesting case report.
AB  - STUDY DESIGN: Case report. CLINICAL QUESTION: To report successful surgical
      therapy for spinal canal stenosis in an adult patient with congenital thoraco
      lumbar kyphoscoliosis with spina bifida aperta and myelomeningocele. METHODS: A
      65-year-old woman with a history of congenital thoraco-lumbar kyphoscoliosis with
      spina bifida aperta and myelomeningocele presented with severe radicular pain and
      weakness in her left lower limb. RESULTS: The patient underwent microsurgical
      decompression at the level of L3/S1 on the left side. Postsurgery, the patient
      showed significant amount of pain relief and improvement in weakness in the left
      lower limb. CONCLUSION: Surgery for spinal canal stenosis in patients with severe
      thoraco-lumbar scoliosis can be effective in relieving radicular pain, weakness
      and numbness, and while not curative can greatly improve the quality of life.

PMID- 22592914
TI  - Functional outcome of limb salvage surgery with mega-endoprosthetic
      reconstruction for bone tumors.
AB  - BACKGROUND: The use of a mega-endoprosthesis has become the method of choice for
      reconstruction after bone tumors. In this study, we sought to determine the
      functional outcome and complications associated with mega-endoprosthesis.
      METHODS: A retrospective review of the charts of 16 patients who had undergone
      resection of bone tumors followed by reconstruction with mega-endoprosthesis
      between 2006 and 2011 was performed. Functional evaluation was based on the
      Musculoskeletal Tumor Society (MSTS) scoring system. Complications of the
      procedures were also analyzed. RESULTS: Eight men and eight women at an average
      age of 36.7 years were included in the study. The tumor involved lower limb in 14
      patients and upper limb in 2 patients. The average MSTS functional score was 72.3
      +/- 15. Excellent results were achieved in six patients, good in five, moderate
      and fair in two each and poor in one. Complications occurred in eight patients.
      Two patients had aseptic loosening of the femoral component of total knee
      replacement. Flap necrosis occurred in two patients, both of whom required
      latissimus dorsi free flap for coverage of total knee prosthesis. One patient
      underwent revision of femoral component subsequent to knee dissociation. Local
      recurrence of tumor, patellar tendon rupture and foot drop occurred in one
      patient each. CONCLUSION: Mega-endoprosthetic reconstruction in limb salvage
      provides good functional outcome in patients with bone tumors.

PMID- 22592915
TI  - Biomechanical effect of graded minimal-invasive decompression procedures on
      lumbar spinal stability.
AB  - INTRODUCTION: Decompression surgery represents the standard operative treatment
      for lumbar spinal stenosis, but this procedure is often combined with fusion
      surgery. It is still discussed whether minimal-invasive decompression procedures
      are sufficient and if they compromise spinal stability as well. The aim of this
      study was to analyze the effects of different minimal-invasive decompression
      procedures on the range of motion (ROM) of the decompressed and adjacent segments
      under preload conditions. METHODS: Fourteen fresh frozen human cadaver lumbar
      spines (L2-L5) were tested in a spinal testing device with a moment of 7.5 N m in
      flexion/extension, lateral bending and rotation with and without a preload. The
      ROM of the decompressed segment L3/4 and the adjacent segments L2/L3 and L4/L5
      was measured intact and after creating a gradual defect with resection of the
      interspinous ligament (ISL), bilateral undercutting decompression, detachment of
      the supraspinous ligament (SSL) and bilateral medial facetectomy. RESULTS: The
      resection of the ISL had no significant effect on the ROM of all segments.
      Undercutting decompression showed a significant increase in the ROM of all
      segments during flexion/extension and lateral bending. The detachment of the SSL
      caused a significant increase of ROM during flexion/extension in the instrumented
      and adjacent segments. After bilateral medial facetectomy, a decrease of ROM was
      observed in all directions of motion except flexion/extension with preload.
      CONCLUSIONS: The results support minimal-invasive procedures for the preservation
      of spinal stability. Therefore, surgeons can determine which grade of
      decompression procedure can be performed in the individual patient without
      requiring additional fusion to maintain spinal stability.

PMID- 22592916
TI  - KLF4 translation level is associated with differentiation stage of different
      pediatric leukemias in both cell lines and primary samples.
AB  - Biomarkers on malignant cells may confer prognostic significance. Kruppel-like
      factor 4 (KLF4) has been reported to be expressed variably on leukemia cells, but
      its expression patterns in leukemias with different differentiation stages and
      its relationships with clinical parameters remain to be elucidated. To examine
      the KLF4 expression pattern in human leukemias and its clinical significance, RT
      PCR and real-time PCR were used to detect KLF4 expression in 9 leukemia cell
      lines and 96 pediatric leukemia patients. KLF4 mRNA expressed in 5/16 (31.25 %)
      of AML patients and 11/28 (39.29 %) ALL patients, significantly lower than that
      in control (9/11, 81.82 %, P < 0.05). The expressions of KLF4 mRNA were much
      lower in ALL (27/52) compared to AML (25/52) (P = 0.019), AML-M1 to other
      subtypes of AML (P = 0.001), C-ALL to Pre-B ALL (P = 0.004), Pro-T ALL to T-ALL
      (P = 0.048). Observation on leukemia cell lines showed the similar pattern. The
      relative expression of KLF4 mRNA was inversely associated with CD34-positive
      rates (r = -0.296, P = 0.037), but it was not associated with the blasts
      percentages in bone marrow (r = -0.222, P = 0.137) and the WBC counts (r = 
      0.058, P = 0.679). KLF4 mRNA expression level was not related to the overall
      survival (r = -0.063, P = 0.670), and the median survival times for the KLF4
      (Lower) and KLF4 (Higher) groups were comparable (28 vs. 25 months, P = 0.265).
      Furthermore, no difference was found in KLF4 mRNA expression levels whether in
      leukemias with normal and abnormal karyotypes (P = 0.180), or in leukemias with
      normal and abnormal molecular cytogenetics (P = 0.591). We conclude that KLF4
      translation level is associated with the differentiation stage of different
      leukemias and is independent of other parameters of risk stratification.

PMID- 22592917
TI  - c-Jun N-terminal kinase mediated VEGFR2 sustained phosphorylation is critical for
      VEGFA-induced angiogenesis in vitro and in vivo.
AB  - c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) is involved in
      the regulation of various cellular functions including cell cycle, proliferation,
      apoptosis. However, whether JNK/SAPK directly regulates the angiogenesis of human
      umbilical vein endothelial cells (HUVECs) induced by vascular endothelial growth
      factor A (VEGFA) has not yet been fully elucidated. Our present study firstly
      demonstrated VEGFA-induced angiogenic responses including the increase of cell
      viability, migration, and tube formation with a concentration-dependent manner in
      HUVECs. Further results showed that VEGFA induced the activation of JNK/SAPK, p38
      kinase and extracellular signal-regulated kinases 1 and 2 (ERK1/2), while
      JNK/SAPK inhibitor SP600125 and specific siRNA both blocked all those angiogenic
      effects induced by VEGFA. Furthermore, VEGFA induced the phosphorylation of ASK1,
      SEK1/MKK4, MKK7, and c-Jun, which are upstream or downstream signals of JNK/SAPK.
      In addition, in vivo matrigel plug assay further showed that SP600125 inhibited
      VEGFA-induced angiogenesis. Further results showed that SP600125 and JNK/SAPK
      siRNA decreased VEGFA-induced VEGFR2 (Flk-1/KDR) sustained phosphorylation in
      HUVECs. Taken together, all these results demonstrate that JNK/SAPK regulates
      VEGFA-induced VEGFR2 sustained phosphorylation, which plays important roles in
      VEGFA-induced angiogenesis in HUVECs.

PMID- 22592918
TI  - The clavicles of Smilodon fatalis and Panthera atrox (Mammalia: Felidae) from
      Rancho La Brea, Los Angeles, California.
AB  - The Rancho La Brea collections at the George C. Page Museum in Los Angeles,
      California, contain the largest single inventory of Smilodon fatalis remains
      representing virtually every bone in the skeleton. Eighteen clavicles of two
      distinctive shapes have been recovered from historical and recent excavations at
      Rancho La Brea. In this study, we identify these specimens to species through
      comparison of their morphology and morphological variability with clavicles found
      in modern felids. This study includes a reevaluation of clavicles that have been
      previously assigned to S. fatalis, which are more likely to be those of Panthera
      atrox, and the description of pantherine cat clavicles. A previously undescribed
      sample of clavicles not only includes some of the same pantherine morph but also
      10 specimens, herein assigned to S. fatalis, which are morphologically
      distinctive and significantly smaller than the previously described specimens. In
      addition, we report unexpected variations between clavicles of Panthera leo and
      P. tigris: the clavicles of P. leo closely resemble those of the large Rancho La
      Brea clavicle morph-which presumably belongs to P. atrox-thus supporting a P.
      leo/P. atrox clade. We report distinctive morphology of the clavicles of Acinonyx
      jubatus. Possible functional and phylogenic significance of felid clavicles is
      suggested.

PMID- 22592919
TI  - Mechanistic insights into the dissolution of spray-dried amorphous solid
      dispersions.
AB  - We have investigated the dissolution mechanisms of spray-dried amorphous solid
      dispersions of the poorly water-soluble drug felodipine and the water-soluble
      polymer copovidone using a new combined spectrophotometric and magnetic resonance
      imaging technique and a mathematical modelling approach. Studies of the
      dissolution rates of both uncompacted and compacted solid dispersions revealed
      that compaction leads to a significant decrease in the rate and extent of
      dissolution and a strong dependence on drug loading, especially for the
      uncompacted samples. Low drug-loaded compacts [5% and 15% (w/w) felodipine]
      eroded with linear kinetics at identical rates, pointing to matrix control,
      whereas for compacts containing a higher proportion of felodipine (>= 30%, w/w),
      dissolution performance was dominated by the drug. In these cases, felodipine
      concentrations were extremely low and the compact swelled rather than eroded. We
      have developed a mathematical population balance framework to model the processes
      of particle release, dissolution and crystal growth. This was found to accurately
      describe the bell-shaped dissolution profiles observed for the compacts
      containing a low felodipine loading.

PMID- 22592920
TI  - Hydrogen sulfide attenuates particulate matter-induced human lung endothelial
      barrier disruption via combined reactive oxygen species scavenging and Akt
      activation.
AB  - Exposure to particulate air pollution is associated with increased
      cardiopulmonary morbidity and mortality, although the pathogenic mechanisms are
      poorly understood. We previously demonstrated that particulate matter (PM)
      exposure triggers massive oxidative stress in vascular endothelial cells (ECs),
      resulting in the loss of EC integrity and lung vascular hyperpermeability. We
      investigated the protective role of hydrogen sulfide (H(2)S), an endogenous
      gaseous molecule present in the circulation, on PM-induced human lung EC barrier
      disruption and pulmonary inflammation. Alterations in EC monolayer permeability,
      as reflected by transendothelial electrical resistance (TER), the generation of
      reactive oxygen species (ROS), and murine pulmonary inflammatory responses, were
      studied after exposures to PM and NaSH, an H(2)S donor. Similar to N-acetyl
      cysteine (5 mM), NaSH (10 MUM) significantly scavenged PM-induced EC ROS and
      inhibited the oxidative activation of p38 mitogen-activated protein kinase.
      Concurrent with these events, NaSH (10 MUM) activated Akt, which helps maintain
      endothelial integrity. Both of these pathways contribute to the protective effect
      of H(2)S against PM-induced endothelial barrier dysfunction. Furthermore, NaSH
      (20 mg/kg) reduced vascular protein leakage, leukocyte infiltration, and
      proinflammatory cytokine release in bronchoalveolar lavage fluids in a murine
      model of PM-induced lung inflammation. These data suggest a potentially
      protective role for H(2)S in PM-induced inflammatory lung injury and vascular
      hyperpermeability.

PMID- 22592921
TI  - Cytokines alter glucocorticoid receptor phosphorylation in airway cells: role of
      phosphatases.
AB  - Corticosteroid insensitivity (CSI) represents a profound challenge in managing
      patients with asthma. We recently demonstrated that short exposure of airway
      smooth muscle cells (ASMCs) to proasthmatic cytokines drastically reduced their
      responsiveness to glucocorticoids (GCs), an effect that was partially mediated
      via interferon regulatory factor-1, suggesting the involvement of additional
      mechanisms (Am J Respir Cell Mol Biol 2008;38:463-472). Although GC receptor (GR)
      can be phosphorylated at multiple serines in the N-terminal region, the major
      phosphorylation sites critical for GR transcriptional activity are serines 211
      (Ser211) and 226 (Ser226). We tested the novel hypothesis that cytokine-induced
      CSI in ASMCs is due to an impaired GR phosphorylation. Cells were treated with
      TNF-alpha (10 ng/ml) and IFN-gamma (500 UI/ml) for 6 hours and/or fluticasone
      (100 nm) added 2 hours before. GR was constitutively phosphorylated at Ser226 but
      not at Ser211 residues. Cytokines dramatically suppressed fluticasone-induced
      phosphorylation of GR on Ser211 but not on Ser226 residues while increasing the
      expression of Ser/Thr protein phosphatase (PP)5 but not that of PP1 or PP2A.
      Transfection studies using a reporter construct containing GC responsive elements
      showed that the specific small interfering RNA-induced mRNA knockdown of PP5, but
      not that of PP1 or PP2A, partially prevented the cytokine suppressive effects on
      GR-meditated transactivation activity. Similarly, cytokines failed to inhibit GC
      induced GR-Ser211 phosphorylation when expression of PP5 was suppressed. We
      propose that the novel mechanism that proasthmatic cytokine-induced CSI in ASMCs
      is due, in part, to PP5-mediated impairment of GR-Ser211 phosphorylation.

PMID- 22592922
TI  - Dual oxidase 2 bidirectional promoter polymorphisms confer differential immune
      responses in airway epithelia.
AB  - The dual oxidase enzymes, DUOX, localized to the respiratory tract epithelium,
      are important components of innate host defense against bacteria and virus.
      However, little is known regarding the regulation of DUOX transcription. To
      better understand DUOX2-mediated mechanisms of antiviral host defense in the
      airway epithelium, we designed a bidirectional promoter luciferase reporter
      system to identify important cis-regulatory regions in the human DUOX2/DUOXA2
      promoter. In this report, we demonstrate that the genomic region between the
      translation start sites of DUOX2 and DUOXA2 functions as a bidirectional promoter
      in human airway tissue. We also identified key regulatory regions on the
      DUOX2/DUOXA2 promoter that were necessary for both bidirectional and
      unidirectional transcriptional activity. Importantly, we discovered two
      functionally important single-nucleotide polymorphisms (SNPs) within the promoter
      that differentially regulated DUOX2/DUOXA2 transcription in response to exogenous
      double-stranded DNA. One of these SNPs, rs269855 (enriched in people of African
      descent), conferred the highest level of DUOX2 promoter activity. The clinical
      sequelae for individuals who carry this polymorphism remain to be determined.

PMID- 22592923
TI  - Delayed resolution of lung inflammation in Il-1rn-/- mice reflects elevated IL
      17A/granulocyte colony-stimulating factor expression.
AB  - IL-1 has been associated with acute lung injury (ALI) in both humans and animal
      models, but further investigation of the precise mechanisms involved is needed,
      and may identify novel therapeutic targets. To discover the IL-1 mediators
      essential to the initiation and resolution phases of acute lung inflammation,
      knockout mice (with targeted deletions for either the IL-1 receptor-1, i.e., Il
      1r1(-/-), or the IL-1 receptor antagonist, i.e., Il-1rn(-/-)) were exposed to
      aerosolized LPS, and indices of lung and systemic inflammation were examined over
      the subsequent 48 hours. The resultant cell counts, histology, protein, and RNA
      expression of key cytokines were measured. Il-1r1(-/-) mice exhibited decreased
      neutrophil influx, particularly at 4 and 48 hours after exposure to LPS, as well
      as reduced bronchoalveolar lavage (BAL) expression of chemokines and granulocyte
      colony-stimulating factor (G-CSF). On the contrary, Il-1rn(-/-) mice demonstrated
      increased BAL neutrophil counts, increased BAL total protein, and greater
      evidence of histologic injury, all most notably 2 days after LPS exposure. Il
      1rn(-/-) mice also exhibited higher peripheral neutrophil counts and greater
      numbers of granulocyte receptor-1 cells in their bone marrow, potentially
      reflecting their elevated plasma G-CSF concentrations. Furthermore, IL-17A
      expression was increased in the BAL and lungs of Il-1rn(-/-) mice after exposure
      to LPS, likely because of increased numbers of gammadelta T cells in the Il-1rn(
      /-) lungs. Blockade with IL-17A monoclonal antibody before LPS exposure decreased
      the resultant BAL neutrophil counts and lung G-CSF expression in Il-1rn(-/-)
      mice, 48 hours after exposure to LPS. In conclusion, Il-1rn(-/-) mice exhibit
      delayed resolution in acute lung inflammation after exposure to LPS, a process
      that appears to be mediated via the G-CSF/IL-17A axis.

PMID- 22592926
TI  - A feature-inversion effect: can an isolated feature show behavior like the face
      inversion effect?
AB  - The face-inversion effect (FIE) is explained by the configural-processing
      hypothesis. It proposes that inversion disrupts configural information processing
      (spatial links among facial features) and leaves the processing of featural
      information (eyes, nose, and mouth) comparatively intact. According to this
      hypothesis, an inverted isolated facial feature cannot show a feature-inversion
      effect--that is, behavior similar to the FIE--since all the spatial links between
      it and the other features in a face are eliminated; that is, the configural
      information is removed. The findings of the present study, which show that
      isolated eyes do exhibit the feature-inversion effect, support the extended
      configural-processing hypothesis. This proposes that inversion also impairs
      processing of the configural information within the eyes themselves. Removal of
      the brows in whole faces tended to interfere with processing of the configural
      information in the upright position but to facilitate processing in the inverted
      position.

PMID- 22592924
TI  - Regulation of airway and alveolar epithelial cell apoptosis by p53-Induced
      plasminogen activator inhibitor-1 during cigarette smoke exposure injury.
AB  - Increased expression of tumor suppressor protein p53 and of plasminogen activator
      inhibitor (PAI)-1 is associated with cigarette smoke (CS) exposure-induced lung
      epithelial injury. p53 induces PAI-1 through mRNA stabilization in lung
      epithelial cells. However, it is unclear how this process affects lung epithelial
      damage. Here, we show that CS induces p53 and PAI-1 expression and apoptosis in
      cultured Beas2B and primary alveolar type (AT)II cells. CS exposure augmented
      binding of p53 protein with PAI-1 mRNA. Inhibition of p53 from binding to PAI-1
      mRNA through expression of p53-binding 70 nt PAI-1 mRNA 3'UTR sequences
      suppressed CS-induced PAI-1 expression. Treatment of Beas2B cells with caveolin-1
      scaffolding domain peptide (CSP) suppressed p53 expression and p53-PAI-1 mRNA
      interaction. These changes were associated with parallel inhibition of CS-induced
      PAI-1 expression and apoptosis in Beas2B cells. Wild-type mice exposed to passive
      CS likewise show augmented p53 and PAI-1 with parallel induction of ATII cell
      apoptosis, whereas mice deficient for p53 or PAI-1 expression resisted apoptosis
      of ATII cells. CSP suppressed CS-induced ATII cell apoptosis in wild-type mice
      and abrogated p53-PAI-1 mRNA interaction with parallel inhibition of p53 and PAI
      1 expression. The protection against ATII cell apoptosis by CSP involves
      inhibition of passive CS-induced proapoptotic Bax and Bak expression and
      restoration of the prosurvival proteins Bcl-X(L). These observations demonstrate
      that inhibition of p53 binding to PAI-1 mRNA 3'UTR attenuates CS-induced ATII
      cell apoptosis. This presents a novel link between p53-mediated PAI-1 expression
      and CS-induced ATII cell apoptosis.

PMID- 22592927
TI  - Development and validation of a mass spectrometric detection method of
      peginesatide in dried blood spots for sports drug testing.
AB  - As recently reported, dried blood spot (DBS) analysis is an advantageous
      technique for doping control purposes due to the minimal invasive sample
      collection, the simple and economic manner, as well as the low susceptibility to
      manipulation. Its general applicability to the sports drug testing arena has been
      shown for analytes of various substance classes, all of which comprise
      exclusively low molecular mass compounds. The aim of the present study was to
      investigate whether the technique of DBS analysis is applicable also to
      (pegylated) peptides with relevance for doping controls. As target analyte,
      peginesatide (Omontys, Hematide), a recently approved pegylated erythropoietin
      mimetic peptide of approximately 45 kDa, tested for the treatment of anaemia in
      patients with renal failure, was chosen, which has been prohibited in elite
      sports due to its assumed endurance enhancing effects. Therefore, a detection
      method for peginesatide employing DBS was developed based on extraction,
      proteolytic digestion and cation-exchange purification followed by liquid
      chromatography-tandem mass spectrometry analysis. Eventually, the assay was
      validated for qualitative purposes and proved to be specific, sensitive (limit of
      detection, 10 ng/mL) and precise (relative standard deviations below 18%),
      demonstrating the general suitability of DBS analysis in sports drug testing also
      for (pegylated) peptides.

PMID- 22592928
TI  - Paternal age effect on age of onset in bipolar I disorder is mediated by sex and
      family history.
AB  - This study investigated for the first time in the psychiatric literature the
      effect of parental age on age-of-onset (AO) in bipolar I disorder (BPI) in
      relation to proband sex and family history (FH) for major psychoses in a sample
      of 564 BPI probands. All probands, 72.68% of their first-degree and 12.13% of
      their second-degree relatives were directly interviewed. The FH-method was used
      for all unavailable relatives. The diagnoses were made according to DSM-IV(TR) .
      The impact of parental age on proband early/late AO was evaluated through
      logistic regression with the cut-off for early AO determined through commingling
      analysis. We found evidence for a significant influence of increasing paternal
      age, and especially age >= 35 years, on AO of BPI disorder in the total sample
      (OR = 0.54, CI: 0.35-0.80), in the female subsample (OR = 0.44, CI: 0.25-0.78),
      in the sporadic subsample (OR = 0.64, CI: 0.38-0.95), and in the subsample with
      FH of recurrent unipolar major depression (Mdd-RUP) (OR = 0.55, CI: 0.34-0.87).
      No significant effect of paternal age on disease AO was found in patients with FH
      of bipolar (BP), schizoaffective disorders (SA), or schizophrenia (SCZ), nor in
      males. Mean age was significantly higher in fathers of sporadic cases and of
      cases with FH of Mdd-RUP than in fathers of cases with FH of BP/SA/SCZ (P =
      0.011). Maternal age had no significant effect either in the total sample or in
      subsamples defined by proband sex or FH. In conclusion, in our sample increasing
      paternal age lowered the onset of BPI selectively, the effect being related to
      the female sex and FH-type.

PMID- 22592925
TI  - Altered dendritic distribution of dopamine D2 receptors and reduction in
      mitochondrial number in parvalbumin-containing interneurons in the medial
      prefrontal cortex of cannabinoid-1 (CB1) receptor knockout mice.
AB  - The prelimbic prefrontal cortex (PL) is a brain region integral to complex
      behaviors that are highly influenced by cannabinoids and by dopamine D2 receptor
      (D2R)-mediated regulation of fast-firing parvalbumin-containing interneurons. We
      have recently shown that constitutive deletion of the cannabinoid-1 receptor
      (CB1R) greatly reduces parvalbumin levels in these neurons. The effects of CB1R
      deletion on PL parvalbumin interneurons may be ascribed to loss of CB1R-mediated
      retrograde signaling on mesocortical dopamine transmission, and, in turn, altered
      expression and/or subcellular distribution of D2R in the PL. Furthermore,
      diminished parvalbumin expression could indicate metabolic changes in fast-firing
      interneurons that may be reflected in changes in mitochondrial density in this
      population. We therefore comparatively examined electron microscopic dual
      labeling of D2R and parvalbumin in CB1 (-/-) and CB1 (+/+) mice to test the
      hypothesis that absence of CB1R produces changes in D2R localization and
      mitochondrial distribution in parvalbumin-containing interneurons of the PL. CB1
      (-/-) mice had a significantly lower density of cytoplasmic D2R-immunogold
      particles in medium parvalbumin-labeled dendrites and a concomitant increase in
      the density of these particles in small dendrites. These dendrites received both
      excitatory and inhibitory-type synapses from unlabeled terminals and contained
      many mitochondria, whose numbers were significantly reduced in CB1 (-/-) mice.
      Non-parvalbumin dendrites showed no between-group differences in either D2R
      distribution or mitochondrial number. These results suggest that cannabinoid
      signaling provides an important determinant of dendritic D2 receptor distribution
      and mitochondrial availability in fast-spiking interneurons.

PMID- 22592929
TI  - A randomized controlled trial for cervical priming using vaginal misoprostol
      prior to hysteroscopy in women who have only undergone cesarean section.
AB  - PURPOSE: To evaluate the efficacy of misoprostol administrated vaginally on
      cervical priming and its complications prior to diagnostic or operative
      hysteroscopy in women who have undergone at least one cesarean section and who
      have never delivered vaginally before and/or had other transcervical procedure.
      METHODS: A total of 55 patients undergoing hysteroscopy for various intra-uterine
      lesions were included in this study and were randomly allocated to two groups
      finally. Thirty patients in the study group were given 200 MUg misoprostol
      vaginally 12 h before the procedure, whereas 25 patients in the control group did
      not receive any cervical priming. The countered outcome included the cervical
      width detected with Hegar dilatators and complication rates. RESULTS: Mean
      cervical width was greater in the study group (6.6 +/- 1.3) than in the control
      group (5.1 +/- 0.9). Complications and failure rates were lower in the study
      group. CONCLUSION: Application of 200 MUg misoprostol vaginally 12 h before
      hysteroscopy softens the cervix, reduces cervical resistance and consequently the
      need for cervical dilatation, with only mild side effects.

PMID- 22592930
TI  - Which is the best MRI marker of malignancy for atypical cirrhotic nodules:
      hypointensity in hepatobiliary phase alone or combined with other features?
      Classification after Gd-EOB-DTPA administration.
AB  - PURPOSE: To investigate whether the malignancy of atypical nodules in cirrhosis
      can be identified at gadoxetic-acid-disodium(Gd-EOB-DTPA)-MRI by their
      hypointensity in the hepatobiliary(HB)-phase alone or combined with any other MR
      imaging features. MATERIALS AND METHODS: One hundred eleven atypical nodules
      detected in 77 consecutive Gd-EOB-DTPA-MRIs were divided, based on arterial-phase
      behavior, into: Class I, isovascular (n = 82), and Class II, hypervascular
      without portal/delayed washout (n = 29). The two classes were further grouped
      based on HB-phase intensity (A/B/C hypo/iso/hyperintensity).
      Portal/venous/equilibrium-phase behavior and T2w features were also collected.
      Histology was the gold standard. Per-nodule sensitivity, specificity, negative
      and positive predictive values (NPV/PPV), and diagnostic accuracy were calculated
      for HB-phase hypointensity alone, and combined with vascular patterns and T2w
      hyperintensity. RESULTS: Histology detected 60 benign and 51
      malignant/premalignant nodules [10 overt hepatocellular carcinomas (HCCs) and 41
      high-grade dysplastic nodules (HGDN)/early HCC]. Class IA contained 31 (94%)
      malignancies, IB one (3%), and IC only benign lesions. Class IIA had 100%
      malignancies, IIB three (37.5%) and IIC only two (28.5%). HB-phase hypointensity
      alone (Classes I-IIA) had 88% sensitivity, 91% NPV, and 93% diagnostic accuracy,
      superior (P < 0.05, P < 0.006, and P < 0.05, respectively) to any other MR
      imaging feature alone or combined. CONCLUSION: In atypical cirrhotic nodules, HB
      phase hypointensity by itself is the strongest marker of malignancy.

PMID- 22592931
TI  - Association between depressive symptoms and negative dependent life events from
      late childhood to adolescence.
AB  - The association between stressful life events and depression has been
      consistently supported in the literature; however, studies of the developmental
      trajectories of these constructs and the nature of their association over time
      are limited. We examined trajectories of depressive symptoms and negative
      dependent life events and the associations between these constructs in a sample
      of 916 youth assessed annually from age 9 to 16, using latent growth curve
      modeling. Youth depressive symptoms, as rated by youth, parents, and teachers,
      decreased from late childhood into adolescence, whereas rates of youth-rated life
      events did not change significantly over time. Initial levels of depressive
      symptoms were positively associated with initial levels of life events.
      Furthermore, after controlling for the initial association between the two
      constructs, increases in depressive symptoms (as assessed by parents and youth)
      were positively associated with increases in life events over time. The study
      builds on prior research by focusing specifically on negative dependent life
      events, examining results across multiple informants, and employing latent growth
      curve modeling to evaluate associations between trajectories of life events and
      depressive symptoms in a longitudinal adolescent sample. Additional studies
      employing latent growth modeling to examine the changes in this association
      during adolescence are needed.

PMID- 22592933
TI  - [Orthodontic treatment need in a representative adult cohort].

PMID- 22592932
TI  - Lifelong environmental enrichment in rats: impact on emotional behavior, spatial
      memory vividness, and cholinergic neurons over the lifespan.
AB  - We assessed lifelong environmental enrichment effects on possible age-related
      modifications in emotional behaviors, spatial memory acquisition, retrieval of
      recent and remote spatial memory, and cholinergic forebrain systems. At the age
      of 1 month, Long-Evans female rats were placed in standard or enriched rearing
      conditions and tested after 3 (young), 12 (middle-aged), or 24 (aged) months.
      Environmental enrichment decreased the reactivity to stressful situations
      regardless of age. In the water maze test, it delayed the onset of learning
      deficits and prevented age-dependent spatial learning and recent memory retrieval
      alterations. Remote memory retrieval, which was altered independently of age
      under standard rearing conditions, was rescued by enrichment in young and middle
      aged, but unfortunately not aged rats. A protected basal forebrain cholinergic
      system, which could well be one out of several neuronal manifestations of
      lifelong environmental enrichment, might have contributed to the behavioral
      benefits of this enrichment.

PMID- 22592935
TI  - Novel systems for in vivo monitoring and microenvironmental investigations of
      diabetic neuropathy in a murine model.
AB  - Peripheral neuropathy is a devastating complication of diabetes conferring vast
      morbidity and mortality. Despite prolonged efforts to elucidate the mechanisms
      underlying diabetic related neuropathic phenomena and develop effective
      therapies, current treatment is for the most part glycemic control and
      symptomatic care. This is partially due to the intricate pathophysiology of
      diabetic neuropathy and the scarcity of valid experimental models. The aim of the
      study was to establish novel systems enabling monitoring and dissection of
      significant processes in the development of diabetic neuropathy. In a non
      invasive in vivo model, two-photon microscopy is applied to evaluate
      mechanoreceptors (Meissner corpuscles) within an intact footpad of transgenic
      mice expressing a fluorescent neuronal tracer. By applying this advanced
      technology, which couples potent tissue penetration with superb resolution, we
      documented qualitative and quantitative diabetes-specific alterations in these
      sensory structures. Detection of such changes previously required laborious
      invasive histopathological techniques. In parallel, we present an ex vivo system
      that mimics the native microenvironment of the nerve ending via a unique co
      culture of primary sensory neurons and thin skin slices. In conjunction with
      innovative high-throughput digital axonal measurements and computerized
      quantification tools, this method enables an unbiased exploration of neuronal
      autonomous and non-autonomous malfunctions. Using this setup we demonstrate that
      while the diabetic nerve retains a near-normal growth and regeneration
      capacities, the diabetic skin exhibits a decreased ability to support axonal
      outgrowth. Thus, an early target organ failure rather than intrinsic neuronal
      failure may initiate the neuropathy. Overall, the illustrated experimental
      platforms may greatly facilitate the holistic investigation of diabetic
      neuropathy.

PMID- 22592936
TI  - Proteasome inhibition leads to early loss of synaptic proteins in neuronal
      culture.
AB  - A dysfunctional ubiquitin proteasome system may be a mediating factor of disease
      progression in Lewy body dementia (LBD). The effects of proteasome inhibition
      using lactacystin and epoxomicin in primary neuronal culture were studied to
      assess the validity of this model to reflect the cortical pathology of LBD.
      Treatment of primary cortical neurons with 5 MUM lactacystin for 24 h led to a 38
      % reduction in the levels of beta-III-tubulin (p < 0.05), a 48 % reduction in the
      levels of synaptophysin (p < 0.05) and a 74 % reduction in the levels of drebrin
      (p < 0.01), when compared to controls. Results for epoxomicin were similar. The
      loss of neuronal protein occurred prior to any loss of mitochondrial activity or
      cell death. The results are reflective of the loss of synapses and the synaptic
      changes observed in LBD, which may be an early event in the neurodegeneration of
      LBD. The similarities with the pathological changes in LBD highlight the
      possibility that this model can potentially provide a platform to test novel
      treatments.

PMID- 22592938
TI  - Photoreduction of mesoporous In2O3: mechanistic model and utility in gas sensing.
AB  - A model is proposed for the drop in electronic resistance of n-type
      semiconducting indium oxide (In(2)O(3)) upon illumination with light (350 nm, 3.5
      eV) as well as for the (light-enhanced) sensitivity of In(2)O(3) to oxidizing
      gases. Essential features of the model are photoreduction and a rate-limiting
      oxygen-diffusion step. Ordered, mesoporous In(2)O(3) with a high specific surface
      area serves as a versatile system for experimental studies. Analytical techniques
      comprise conductivity measurements under a controlled atmosphere (synthetic air,
      pure N(2)) and temperature-resolved in-situ Fourier transform infrared (FTIR)
      spectroscopy. IR measurements reveal that oxygen vacancies form a donor level
      0.18 eV below the conduction band.

PMID- 22592937
TI  - The effect of piribedil on L-DOPA-induced dyskinesias in a rat model of
      Parkinson's disease: differential role of alpha(2) adrenergic mechanisms.
AB  - Piribedil is a non-ergoline, dopamine D(2)/D(3) receptor agonist with alpha(2)
      adrenoceptor antagonist properties that has been used in the treatment of
      Parkinson's disease (PD). Noradrenergic neurotransmission may be involved in the
      pathogenesis of dyskinesias induced by chronic treatment with L-DOPA (3,4
      dihydroxyphenylalanine, levodopa), but its role in the in vivo action of
      piribedil or on different subclasses of abnormal involuntary movements (AIMs)
      remains unclear. The aims of this study were therefore (1) to investigate the
      anti-dyskinetic effects of piribedil on L-DOPA-induced contralateral turning
      behaviour, locomotive dyskinesias (LD), axial dystonia (AD), orolingual
      dyskinesia (OD) and forelimb dyskinesia (FD) and (2) to compare these effects to
      the alpha(2) adrenoceptor antagonist, idazoxan, or the alpha(2) adrenoceptor
      agonist, clonidine. Rats were unilaterally lesioned with 6-hydroxydopamine (6
      OHDA) and injected intraperitoneally twice daily with L-DOPA methylester (12.5
      mg/kg) and benserazide (3.25 mg/kg). After 3 weeks, the effects of piribedil (5,
      15, 40 mg/kg), clonidine (0.15 mg/kg), idazoxan (10 mg/kg) and combinations of
      these drugs were scored during 2 h. Pre-treatment with 5 and 40 mg/kg, but not 15
      mg/kg, of piribedil reduced turning behaviour and AD, OD and FD, but piribedil
      increased LD at the 40 mg/kg doses compared to the L-DOPA group. Idazoxan induced
      similar effects as piribedil (40 mg/kg), except that it had no effect on LD.
      Idazoxan blocked the effect of piribedil on AD and FD. Clonidine reduced all AIMs
      except OD, possibly because of its sedative effect. Clonidine blocked the effect
      of piribedil on AD, OD and FD. These data suggest a differential involvement of
      alpha(2) adrenergic receptors in the action of piribedil on different subclasses
      of L-DOPA-induced dyskinesias.

PMID- 22592940
TI  - Lack of specialist diabetes teams in hospitals is "absolutely disgraceful," says
      NHS clinical lead.

PMID- 22592939
TI  - Targeting pancreatic progenitor cells in human embryonic stem cell
      differentiation for the identification of novel cell surface markers.
AB  - New sources of beta cells are needed in order to develop cell therapies for
      patients with diabetes. An alternative to forced expansion of post-mitotic beta
      cells is the induction of differentiation of stem-cell derived progenitor cells
      that have a natural self-expansion capacity into insulin-producing cells. In
      order to learn more about these progenitor cells at different stages along the
      differentiation process in which they become progressively more committed to the
      final beta cell fate, we took the approach of identifying, isolating and
      characterizing stage specific progenitor cells. We generated human embryonic stem
      cell (HESC) clones harboring BAC GFP reporter constructs of SOX17, a definitive
      endoderm marker, and PDX1, a pancreatic marker, and identified subpopulations of
      GFP expressing cells. Using this approach, we isolated a highly enriched
      population of pancreatic progenitor cells from hESCs and examined their gene
      expression with an emphasis on the expression of stage-specific cell surface
      markers. We were able to identify novel molecules that are involved in the
      pancreatic differentiation process, as well as stage-specific cell markers that
      may serve to define (alone or in combination with other markers) a specific
      pancreatic progenitor cell. These findings may help in optimizing conditions for
      ultimately generating and isolating beta cells for transplantation therapy.

PMID- 22592941
TI  - High-resolution human diffusion tensor imaging using 2-D navigated multishot
      SENSE EPI at 7 T.
AB  - The combination of parallel imaging with partial Fourier acquisition has greatly
      improved the performance of diffusion-weighted single-shot EPI and is the
      preferred method for acquisitions at low to medium magnetic field strength such
      as 1.5 or 3 T. Increased off-resonance effects and reduced transverse relaxation
      times at 7 T, however, generate more significant artifacts than at lower magnetic
      field strength and limit data acquisition. Additional acceleration of k-space
      traversal using a multishot approach, which acquires a subset of k-space data
      after each excitation, reduces these artifacts relative to conventional single
      shot acquisitions. However, corrections for motion-induced phase errors are not
      straightforward in accelerated, diffusion-weighted multishot EPI because of phase
      aliasing. In this study, we introduce a simple acquisition and corresponding
      reconstruction method for diffusion-weighted multishot EPI with parallel imaging
      suitable for use at high field. The reconstruction uses a simple modification of
      the standard sensitivity-encoding (SENSE) algorithm to account for shot-to-shot
      phase errors; the method is called image reconstruction using image-space
      sampling function (IRIS). Using this approach, reconstruction from highly aliased
      in vivo image data using 2-D navigator phase information is demonstrated for
      human diffusion-weighted imaging studies at 7 T. The final reconstructed images
      show submillimeter in-plane resolution with no ghosts and much reduced blurring
      and off-resonance artifacts.

PMID- 22592942
TI  - Genetic and environmental causes of variation in perceived loneliness in young
      people.
AB  - Loneliness is prevalent in adolescence, despite the widespread expectation
      directed to young people to start building close relationships beyond the nuclear
      family. The aim of the present study was to explore the causal genetic and
      environmental structure behind variability in adolescents' perceived loneliness.
      Seven national cohorts (ages 12-18 years) of Norwegian twins reared together
      (1,394 twin pairs) participated. Perceived loneliness was measured with five
      items from the UCLA Loneliness Scale. Data were collected from mothers, fathers,
      and twins' self ratings by means of a posted questionnaire. Biometric analyses
      were applied, testing the causal architecture of loneliness within a psychometric
      model with one common latent factor in addition to specific genetic and
      environmental sources influencing the scores of each informant. The results
      showed a heritability (h(2)) of 75% on the latent perceived loneliness factor,
      and nonshared environmental effects (e(2)) explaining the remaining 25% of the
      latent factor variance. There were also significant rater-specific genetic and
      nonshared environmental effects. No shared environmental effects were found in
      the model, and there were no sex differences in the estimates. This study showed
      that variation in perceived loneliness in adolescents is highly genetic.
      Additional genetic and nonshared environmental etiological sources are to some
      extent represented in the scores of the specific rater.

PMID- 22592943
TI  - The incidence of metastasis from cutaneous squamous cell carcinoma and the impact
      of its risk factors.
AB  - BACKGROUND: Cutaneous squamous cell carcinoma (cSCC), the most common cancer
      capable of metastasis, has variable reported metastatic rates and the impact of
      individual risk factors for metastasis is unknown. METHODS: This study examined
      pathology records of excised cSCC over a 10-year period. Uni-variate and multi
      variate analyses including patient demographics, maximum clinical diameter (MCD),
      anatomical sub-site, histological differentiation, perineural invasion (PNI), and
      lymphovascular invasion (LVI) of the lesion were performed. The primary endpoint
      was time to metastasis. RESULTS: Six thousand one hundred sixty four patients
      (median age 74 years) underwent excision of 8,997 primary cSCC. During the median
      follow-up of 70 months, the metastatic rate of cSCC was 1.9-2.6%. Multi-variate
      analysis showed that MCD (hazards ratio 1.41 [95% CI 1.25-1.60] P < 0.001), PNI
      (5.29; P < 0.0001), poor histological differentiation (4.26; P < 0.0001),
      location in the ear and retro-auricular area (3.31 [1.17-9.33]; P = 0.0024),
      cheek (3.18 [1.15-8.81]; P = 0.026), and lip (4.84; P = 0.009) increased the risk
      of metastasis. CONCLUSIONS: We show a 1.9-2.6% metastatic rate for cSCC with MCD,
      histologic differentiation, PNI, and certain anatomical sub-sites being
      independent risk factors for metastasis. A prospective study on our proposed risk
      stratification scheme based on these parameters may lead to identification of
      high-risk lesions that would benefit from more intensive treatment and/or routine
      post-operative follow-up.Inc.

PMID- 22592944
TI  - Statistical security for Social Security.
AB  - The financial viability of Social Security, the single largest U.S. government
      program, depends on accurate forecasts of the solvency of its intergenerational
      trust fund. We begin by detailing information necessary for replicating the
      Social Security Administration's (SSA's) forecasting procedures, which until now
      has been unavailable in the public domain. We then offer a way to improve the
      quality of these procedures via age- and sex-specific mortality forecasts. The
      most recent SSA mortality forecasts were based on the best available technology
      at the time, which was a combination of linear extrapolation and qualitative
      judgments. Unfortunately, linear extrapolation excludes known risk factors and is
      inconsistent with long-standing demographic patterns, such as the smoothness of
      age profiles. Modern statistical methods typically outperform even the best
      qualitative judgments in these contexts. We show how to use such methods,
      enabling researchers to forecast using far more information, such as the known
      risk factors of smoking and obesity and known demographic patterns. Including
      this extra information makes a substantial difference. For example, by improving
      only mortality forecasting methods, we predict three fewer years of net surplus,
      $730 billion less in Social Security Trust Funds, and program costs that are
      0.66% greater for projected taxable payroll by 2031 compared with SSA
      projections. More important than specific numerical estimates are the advantages
      of transparency, replicability, reduction of uncertainty, and what may be the
      resulting lower vulnerability to the politicization of program forecasts. In
      addition, by offering with this article software and detailed replication
      information, we hope to marshal the efforts of the research community to include
      ever more informative inputs and to continue to reduce uncertainties in Social
      Security forecasts.

PMID- 22592945
TI  - Organization of antennal lobe-associated neurons in adult Drosophila melanogaster
      brain.
AB  - The primary olfactory centers of both vertebrates and insects are characterized
      by glomerular structure. Each glomerulus receives sensory input from a specific
      type of olfactory sensory neurons, creating a topographic map of the odor
      quality. The primary olfactory center is also innervated by various types of
      neurons such as local neurons, output projection neurons (PNs), and centrifugal
      neurons from higher brain regions. Although recent studies have revealed how
      olfactory sensory input is conveyed to each glomerulus, it still remains unclear
      how the information is integrated and conveyed to other brain areas. By using the
      GAL4 enhancer-trap system, we conducted a systematic mapping of the neurons
      associated with the primary olfactory center of Drosophila, the antennal lobe
      (AL). We identified in total 29 types of neurons, among which 13 are newly
      identified in the present study. Analyses of arborizations of these neurons in
      the AL revealed how glomeruli are linked with each other, how different PNs link
      these glomeruli with multiple secondary sites, and how these secondary sites are
      organized by the projections of the AL-associated neurons.

PMID- 22592946
TI  - From pathophysiological aspects towards unravelling the neurobiological
      background of cognitive deficits.

PMID- 22592948
TI  - Rectal Cancer: MR imaging of the mesorectal fascia and effect of chemoradiation
      on assessment of tumor involvement.
AB  - PURPOSE: To evaluate the impact of chemoradiation on the reliability of MRI in
      assessing tumor involvement of the mesorectal fascia in patients with rectal
      cancer. MATERIALS AND METHODS: Presurgical MRI was performed in 150 patients;
      among them 85 had received neoadjuvant long-course chemoradiation. A standardized
      imaging protocol (1.5 Tesla [T] system, image voxel size 0.6 * 0.4 * 3 mm(3) ),
      standardized surgery, and histopathological examination were applied for the
      entire patient population. Images were analyzed to identify potential tumor
      involvement of the mesorectal fascia (minimum tumor distance to fascia <=1 mm)
      and compared with histopathology as the reference standard. Results of
      nonirradiated and irradiated patients were compared to define the impact of
      chemoradiation on imaging reliability. RESULTS: In nonirradiated patients, MRI
      was reliable in predicting or excluding tumor involvement of the mesorectal
      fascia, positive predictive value 80%, negative predictive value 89%. The
      frequency of overestimating tumor involvement was significantly higher in
      irradiated patients (P = 0.005, positive predictive value 42%). CONCLUSION:
      Discussions about MRI assessment of tumor involvement of the mesorectal fascia as
      a basis for recommending neoadjuvant chemoradiation should focus on
      investigations that excluded irradiated patients, because MRI is less reliable
      after chemoradiation and tends to overestimate mesorectal tumor involvement.

PMID- 22592947
TI  - A versatile method for preparation of hydrated microbial-latex biocatalytic
      coatings for gas absorption and gas evolution.
AB  - We describe a latex wet coalescence method for gas-phase immobilization of
      microorganisms on paper which does not require drying for adhesion. This method
      reduces drying stresses to the microbes. It is applicable for microorganisms that
      do not tolerate desiccation stress during latex drying even in the presence of
      carbohydrates. Small surface area, 10-65 MUm thick coatings were generated on
      chromatography paper strips and placed in the head-space of vertical sealed tubes
      containing liquid to hydrate the paper. These gas-phase microbial coatings
      hydrated by liquid in the paper pore space demonstrated absorption or evolution
      of H2, CO, CO2 or O2. The microbial products produced, ethanol and acetate,
      diffuse into the hydrated paper pores and accumulate in the liquid at the bottom
      of the tube. The paper provides hydration to the back side of the coating and
      also separates the biocatalyst from the products. Coating reactivity was
      demonstrated for Chlamydomonas reinhardtii CC124, which consumed CO2 and produced
      10.2 +/- 0.2 mmol O2 m-2 h-1, Rhodopseudomonas palustris CGA009, which consumed
      acetate and produced 0.47 +/- 0.04 mmol H2 m-2 h-1, Clostridium ljungdahlii OTA1,
      which consumed 6 mmol CO m-2 h-1, and Synechococcus sp. PCC7002, which consumed
      CO2 and produced 5.00 +/- 0.25 mmol O2 m-2 h-1. Coating thickness and
      microstructure were related to microbe size as determined by digital micrometry,
      profilometry, and confocal microscopy. The immobilization of different
      microorganisms in thin adhesive films in the gas phase demonstrates the utility
      of this method for evaluating genetically optimized microorganisms for gas
      absorption and gas evolution.

PMID- 22592949
TI  - Relevance of angiogenesis in neuroendocrine tumors.
AB  - While traditional cytotoxic drugs have shown limited efficacy in neuroendocrine
      tumors (NETs), their biological features have been characterized and can be
      exploited therapeutically. Their most prominent trait is an extraordinary
      vascularization in low-grade NETs and an hypoxia-dependent angiogenesis in high
      grade NETs, which is associated to a significant expression of many proangiogenic
      molecules. Therefore, several antiangiogenic compounds have been tested in these
      malignancies, and among these, sunitinib has demonstrated activity in pancreatic
      NET patients by dually targeting the VEGFR and PDGFR pathways. In spite of these
      efficacious clinical results, apparent resistance to antiangiogenic therapies has
      been described in NET animal models and in clinical trials. Therefore, overcoming
      antiangiogenic resistance is a crucial step in the subsequent development of
      antiangiogenic therapies. Several strategies have been postulated to fight
      resistance, but preclinical studies and clinical trials will investigate and
      address these therapeutic approaches in the coming years in order to overcome
      resistance to antiangiogenic therapies in NETs.

PMID- 22592950
TI  - Chronic therapy in gastrointestinal stromal tumours (GISTs): the big gap between
      theory and practice.
AB  - The advent of imatinib mesilate, an oral target therapy, has dramatically changed
      the natural history of gastrointestinal stromal tumours (GISTs). This rare
      neoplasm has become the paradigm of targeted therapies in solid tumours, also
      introducing a home-based cure concept in oncology. However, it should be retained
      that oral drug administration entails new and relevant management problems.
      Multiple studies have demonstrated the efficacy of imatinib in GISTs associated
      with a good toxicity profile. However, the efficacy of imatinib, according to its
      mechanism of action and pharmacokinetics, is closely related to daily assumption.
      No interruption or "jerky" assumption is permitted in order to avoid efficacy
      loss. Thus, the issue of treatment adherence is crucial for a successful strategy
      and should not be overlooked. We think that dealing with the problem means
      assessing a wide spectrum of not only clinical and general but also psychological
      and individual aspects. Furthermore, both patient and family should play an
      active role in the "cure process" and physicians should reduce the distance
      separating them from their patients due to home-based target therapy, promoting
      communication and consolidation of a trust-based physician-patient relationship.
      Several advantages have been introduced by oral target therapies in oncology.
      However, chronic drug administration, even if generally well tolerated, when
      prolonged for an undetermined time could heavily impact on patients' quality of
      life. This could induce non-prescribed drug suspension, with negative impact on
      disease control. More studies would be necessary in order to detect real
      patients' adherence, to correlate drug assumption with clinical outcome and to
      optimize imatinib treatment strategy.

PMID- 22592951
TI  - Synthesis, structure, properties, and application of a carbazole-based
      diaza[7]helicene in a deep-blue-emitting OLED.
AB  - A carbazole-based diaza[7]helicene, 2,12-dihexyl-2,12-diaza[7]helicene (1), was
      synthesized by a photochemical synthesis and its use as a deep-blue dopant
      emitter in an organic light-emitting diode (OLED) was examined. Compound 1
      exhibited good solubility and excellent thermal stability with a high
      decomposition temperature (T(d)=372.1  degrees C) and a high glass-transition
      temperature (T(g), up to 203.0  degrees C). Single-crystal structural analysis of
      the crystalline clathrate (1)(2)?cyclohexane along with a theoretical
      investigation revealed a non-planar-fused structure of compound 1, which
      prevented the close-packing of molecules in the solid state and kept the molecule
      in a good amorphous state, which allowed the optimization of the properties of
      the OLED. A device with a structure of ITO/NPB (50 nm)/CBP:5 % 1 (30 nm)/BCP (20
      nm)/Mg:Ag (100 nm)/Ag (50 nm) showed saturated blue light with Commission
      Internationale de L'Eclairage (CIE) coordinates of (0.15, 0.10); the maximum
      luminance efficiency and brightness were 0.22 cd A(-1) (0.09 Lm W(-1)) and 2365
      cd m(-2), respectively. This new class of helicenes, based on carbazole
      frameworks, not only opens new possibilities for utilizing helicene derivatives
      in deep-blue-emitting OLEDs but may also have potential applications in many
      other fields, such as molecular recognition and organic nonlinear optical
      materials.

PMID- 22592952
TI  - Treatments for neurodevelopmental disorders: evidence, advocacy, and the
      Internet.
AB  - The Internet is a major source of health-related information for parents of sick
      children despite concerns surrounding quality. For neurodevelopmental disorders,
      the websites of advocacy groups are a largely unexamined source of information.
      We evaluated treatment information posted on nine highly-trafficked advocacy
      websites for autism, cerebral palsy, and fetal alcohol spectrum disorder. We
      found that the majority of claims about treatment safety and efficacy were
      unsubstantiated. Instead, a range of rhetorical strategies were used to imply
      scientific support. When peer-reviewed publications were cited, 20 % were
      incorrect or irrelevant. We call for new partnerships between advocacy and
      experts in developmental disorders to ensure better accuracy and higher
      transparency about how treatment information is selected and evidenced on
      advocacy websites.

PMID- 22592953
TI  - [Anticoagulation. Modern concepts].
AB  - An effective oral anticoagulation with vitamin K antagonists is currently a
      successfully used standard therapy in patients with atrial fibrillation (AF)
      yielding a 60-70% relative reduction in stroke risk compared with placebo, when
      an international normalized ratio (INR) value between 2.0 and 3.0 is maintained.
      However, these agents have a number of well documented shortcomings which
      partially result in a reduced compliance as well as an insufficient INR
      adjustment. A number of new drugs for oral anticoagulation including direct
      factor Xa inhibitors, such as rivaroxaban and direct thrombin inhibitors, such as
      dabigatran have shown promising results, including higher efficacy and
      significantly lower incidences of intracranial bleeding compared with warfarin.
      The new substances show similar results in secondary as well as in primary stroke
      prevention in patients with AF and therefore offer a number of advantages over
      warfarin, including a favorable bleeding profile and convenience of use.
      Consideration of these new anticoagulants might be a good option.

PMID- 22592954
TI  - Synthesis and antioxidant activity of a new class of bis and tris heterocycles.
AB  - A series of novel heterocycles, bisbenzoxazolyl/benzothiazolyl/benzimidazolyl
      pyrazoles/isoxazoles/pyrimidines were synthesized and evaluated for their
      antioxidant activity. The bisbenzoxazolylisoxazole 10 exhibited good antioxidant
      activity when compared with the standard ascorbic acid.

PMID- 22592955
TI  - Mild cognitive impairment identified in older individuals with Down syndrome by
      reduced telomere signal numbers and shorter telomeres measured in microns.
AB  - Previously, we established that short-term T lymphocyte cultures from people with
      Down syndrome (DS) and dementia (Alzheimer's disease) had shorter telomeres than
      did those from age- and sex-matched people with DS only, quantified as
      significantly reduced numbers of signals of peptide nucleic acid (PNA) telomere
      probes in whole metaphases [Jenkins et al. (2008); Neurosci Lett 440:340-343] as
      well as reduced telomere probe light intensity values in interphases [Jenkins et
      al. (2010); Neurobiol Aging 31:765-771]. We now describe shorter telomere length
      in adults with DS and mild cognitive impairment (MCI) compared to age- and sex
      matched individuals with DS without MCI. Telomere length is quantified by reduced
      telomere signal numbers and shorter chromosome 1 telomeres measured in
      micrometers (microns). These findings were in agreement with quantitative light
      intensity measurements of chromosome 1 and chromosome 21 PNA telomere probes with
      and without the use of a "normalizing ratio" involving the fluorescence exhibited
      by a PNA probe for centromere 2, and with the use of light intensity measurements
      of interphase preparations. Most importantly, the distributions of chromosome 1
      telomere lengths (in microns) were completely non-overlapping for adults with and
      without MCI, indicating that this measure has great promise as a biomarker for
      MCI as well as dementia in this population.

PMID- 22592956
TI  - Design of a phase III clinical trial with prospective biomarker validation: SWOG
      S0819.
AB  - The role of cetuximab in the treatment of advanced non-small cell lung cancer
      (NSCLC) is currently unclear. The molecular target of cetuximab, epidermal growth
      factor receptor (EGFR), as measured by FISH, has shown potential as a predictive
      biomarker for cetuximab efficacy in NSCLC. SWOG S0819 is a phase III trial
      evaluating both the value of cetuximab in this setting and EGFR FISH as a
      predictive biomarker. This work describes the decision process for determining
      the design and interim monitoring plan for S0819. Six possible designs were
      evaluated in terms of their properties and the hypotheses that can be addressed
      within the design constraints. A subgroup-focused, multiple-hypothesis design was
      selected for S0819 that incorporates coprimary endpoints to assess cetuximab in
      both the overall study population and among EGFR FISH-positive (FISH(+))
      patients, with the sample size determined based on evaluation in the EGFR FISH(+)
      group. The chosen interim monitoring plan specifies interim evaluations of both
      efficacy and futility in the EGFR FISH(+) group alone. The futility-monitoring
      plan to determine early stopping in the EGFR FISH-nonpositive group is based on
      evaluation within the positive group, the entire study population, and the
      nonpositive group. SWOG S0819 uses a design that addresses both the biomarker
      driven and general-efficacy objectives of this study.

PMID- 22592958
TI  - RNA silencing suppressor Pns11 of rice gall dwarf virus induces virus-like
      symptoms in transgenic rice.
AB  - Transgenic rice (Oryza sativa) plants expressing the Pns11 protein of rice gall
      dwarf virus (RGDV) displayed multiple abnormal phenotypes, some of which were
      highly reminiscent of the symptoms observed in RGDV-infected rice. Further
      analysis indicated that the apparent alterations in plant growth and morphology
      were correlated with the expression levels of microRNA160, microRNA162,
      microRNA167, microRNA168, and the microRNA target OsARF8. Especially, the
      striking dwarfing phenotype depended on the high expression level of microRNA167.
      By analogy to other categories of plant viruses, the RNA silencing suppressors
      encoded by plant dsRNA viruses function as pathogenicity determinants. These
      findings significantly deepen our current mechanistic understanding of the RNA
      silencing suppressor (VSR) encoded by a dsRNA virus and provide additional
      evidence that interference with microRNA expression is a VSR function utilized by
      a diverse range of viruses.

PMID- 22592959
TI  - Tepovirus, a novel genus in the family Betaflexiviridae.
AB  - Tepovirus is a new monotypic genus of plant viruses typified by potato virus T
      (PVT), a virus with helically constructed filamentous particles that are 640 nm
      long, previously classified as unassigned species in the family Betaflexiviridae.
      Virions have a single-stranded positive-sense polyadenylated RNA genome that is
      6.5 kb in size, and a single type of coat protein with a size of 24 kDa. The
      viral genome contains three slightly overlapping ORFs encoding, respectively, the
      replication-related proteins (ORF1), a putative movement protein of the 30 K type
      (ORF2) and the coat protein (ORF3). Its structure and organization (number and
      order of genes) resembles that of trichoviruses and of citrus leaf blotch virus
      (CLBV, genus Citrivirus) but has a smaller size. Besides potato, the primary
      host, PVT can experimentally infect herbaceous hosts by mechanical inoculation.
      No vector is known, and transmission is through propagating material (tubers),
      seeds and pollen. PVT has a number of biological, physical and molecular
      properties that differentiate it from betaflexiviruses with a 30K-type movement
      protein. It is phylogenetically distant from all these viruses, but least so from
      grapevine virus A (GVA), the type member of the genus Vitivirus, with which it
      groups in trees constructed using the sequences of all of the genes.

PMID- 22592960
TI  - The sea lamprey UNC5 receptors: cDNA cloning, phylogenetic analysis and
      expression in reticulospinal neurons at larval and adult stages of development.
AB  - UNC5 receptors mediate repulsive signaling of netrin on neurons. Although only
      one UNC5 receptor has been identified in invertebrates, four members of the UNC5
      family have been identified in gnathostomes. Lampreys, together with mixynes,
      belong to the oldest branch of extant vertebrates, and their phylogenetic
      position near to the vertebrate root makes them an interesting model for
      understanding molecular evolution. Here, we cloned three sea lamprey UNC5 (UNC5L)
      receptors, and phylogenetic analyses indicated that the first two duplications of
      the ancestral UNC5 gene occurred before the separation of jawless and jawed
      vertebrates. UNC5 receptors play important roles during early development, but
      expression studies have also suggested that UNC5 receptors play roles in the
      mature nervous system. Here, we report the expression of the different UNC5L
      receptor transcripts in identified reticulospinal neurons of mature larval or
      adult sea lampreys detected by in situ hybridization in wholemounted brain
      preparations. In addition, an extensive expression of the UNC5 receptors was also
      observed in most brain regions of the adult lamprey. An increase in the types of
      identifiable reticulospinal neurons expressing the UNC5L receptors was observed
      in adults compared with larvae. Expression of UNC5 receptors at late
      developmental stages appears to be a shared characteristic of lampreys and
      mammals. In larvae, expression of UNC5L receptors was observed in reticulospinal
      neurons that when axotomized are known to be "bad regenerators." Results in
      lampreys and mammals suggest that the UNC5-Netrin axonal guidance system may play
      a role in limiting axonal regeneration after spinal cord injury.

PMID- 22592957
TI  - The contribution of rodent models to the pathological assessment of flaviviral
      infections of the central nervous system.
AB  - Members of the genus Flavivirus are responsible for a spectrum of important
      neurological syndromes in humans and animals. Rodent models have been used
      extensively to model flavivirus neurological disease, to discover host-pathogen
      interactions that influence disease outcome, and as surrogates to determine the
      efficacy and safety of vaccines and therapeutics. In this review, we discuss the
      current understanding of flavivirus neuroinvasive disease and outline the host,
      viral and experimental factors that influence the outcome and reliability of
      virus infection of small-animal models.

PMID- 22592961
TI  - Evaluation of partnership working in cities in phase IV of the WHO Healthy Cities
      Network.
AB  - An intersectoral partnership for health improvement is a requirement of the WHO
      European Healthy Cities Network of municipalities. A review was undertaken in 59
      cities based on responses to a structured questionnaire covering phase IV of the
      network (2003-2008). Cities usually combined formal and informal working
      partnerships in a pattern seen in previous phases. However, these encompassed
      more sectors than previously and achieved greater degrees of collaborative
      planning and implementation. Additional WHO technical support and networking in
      phase IV significantly enhanced collaboration with the urban planning sector.
      Critical success factors were high-level political commitment and a well
      organized Healthy City office. Partnerships remain a successful component of
      Healthy City working. The core principles, purpose and intellectual rationale for
      intersectoral partnerships remain valid and fit for purpose. This applied to long
      established phase III cities as well as newcomers to phase IV. The network, and
      in particular the WHO brand, is well regarded and encourages political and
      organizational engagement and is a source of support and technical expertise. A
      key challenge is to apply a more rigorous analytical framework and theory
      informed approach to reviewing partnership and collaboration parameters. 

PMID- 22592962
TI  - Fluorine-directed beta-galactosylation: chemical glycosylation development by
      molecular editing.
AB  - Validation of the 2-fluoro substituent as an inert steering group to control
      chemical glycosylation is presented. A molecular editing study has revealed that
      the exceptional levels of diastereocontrol in glycosylation processes by using 2
      fluoro-3,4,6-tri-O-benzyl glucopyranosyl trichloroacetimidate (TCA) scaffolds are
      a consequence of the 2R,3S,4S stereotriad. This study has also revealed that
      epimerization at C4, results in a substantial enhancement in beta-selectivity (up
      to beta/alpha 300:1).

PMID- 22592963
TI  - A multimodal imaging approach to the evaluation of post-traumatic epilepsy.
AB  - OBJECT: Electroencephalography-functional magnetic resonance imaging (EEG-fMRI)
      coregistration and high-density EEG (hdEEG) can be combined to map noninvasively
      abnormal brain activation elicited by epileptic processes. By combining
      noninvasive imaging techniques in a multimodal approach, we sought to investigate
      pathophysiological mechanisms underlying epileptic activity in seven patients
      with severe traumatic brain injury. MATERIALS AND METHODS: Standard EEG and fMRI
      data were acquired during a single scanning session. The EEG-fMRI data were
      analyzed using the general linear model and independent component analysis.
      Source localization of interictal epileptiform discharges (IEDs) was performed
      using 256-channel hdEEG. Blood oxygenation level dependent (BOLD) localizations
      were then compared to EEG source reconstruction. RESULTS: On hdEEG, focal source
      localization was detected in all seven patients; in six out of seven it was
      concordant with the expected epileptic activity as defined by EEG data and
      clinical evaluation; and in four out of seven in whom IEDs were recorded, BOLD
      signal changes were observed. These activities were partially concordant with the
      source localization. CONCLUSION: Multimodal integration of EEG-fMRI and hdEEG
      combining two different methods to localize the same epileptic foci appears to be
      a promising tool to noninvasively map abnormal brain activation in patients with
      post-traumatic brain injury.

PMID- 22592964
TI  - Oxidative stress and antioxidant responses of liver and kidney tissue after
      implantation of titanium or titanium oxide coated plate in rat tibiae.
AB  - Coating with titanium oxides is a promising method to improve the blood
      compatibility of materials to be used for medical implants. However,
      biodegradation of the coating can result in microparticles that subsequently
      cause oxidative stress. Therefore, the present study was carried out to throw
      some light on the mechanisms affecting the reaction of tissue surroundings Ti
      implants either in the form of titanium oxide or not in tibiae of rats. The serum
      collected twice from animals during the period of study and rats were sacrificed
      after two months of implantation. The complete blood picture, total proteins
      content and the activities of some serum enzymes were determined as liver
      biomarker. Kidney function was examined by measuring the levels of serum
      creatinine and uric acid. The level of lipid peroxidation and the activities of
      superoxide dismutase, catalase and glutathione S-transferase as well as
      glutathione content in liver and kidney tissue were evaluated. It has been
      indicated that the lipid peroxidation is one of the molecular mechanisms involved
      in Ti-plate induced cytotoxicity however; the TiO(2)-plate did not. The
      biodegradation of Ti-plate was very slow that could explain why the all enzymatic
      and non-enzymatic antioxidant not affected by implantation of Ti-plate. The total
      antioxidant level in serum was better in rats had TiO(2)/Ti-plate than those
      animals that had Ti-plate. The coating of titanium implants with titanium oxide
      leads to attaining of reduced the oxidative state in the cells, which enhance the
      healing process in comparison with the uncoated implants.

PMID- 22592965
TI  - Dual-source dual-power electrospinning and characteristics of multifunctional
      scaffolds for bone tissue engineering.
AB  - Electrospun tissue engineering scaffolds are attractive due to their distinctive
      advantages over other types of scaffolds. As both osteoinductivity and
      osteoconductivity play crucial roles in bone tissue engineering, scaffolds
      possessing both properties are desirable. In this investigation, novel
      bicomponent scaffolds were constructed via dual-source dual-power electrospinning
      (DSDPES). One scaffold component was emulsion electrospun poly(D,L-lactic acid)
      (PDLLA) nanofibers containing recombinant human bone morphogenetic protein (rhBMP
      2), and the other scaffold component was electrospun calcium phosphate (Ca-P)
      particle/poly(lactic-co-glycolic acid) (PLGA) nanocomposite fibers. The mass
      ratio of rhBMP-2/PDLLA fibers to Ca-P/PLGA fibers in bicomponent scaffolds could
      be controlled in the DSDPES process by adjusting the number of syringes used to
      supply solutions for electrospinning. Through process optimization, both types of
      fibers could be evenly distributed in bicomponent scaffolds. The structure and
      properties of each type of fibers in the scaffolds were studied. The
      morphological and structural properties and wettability of scaffolds were
      assessed. The effects of emulsion composition for rhBMP-2/PDLLA fibers and mass
      ratio of fibrous components in bicomponent scaffolds on in vitro release of rhBMP
      2 from scaffolds were investigated. In vitro degradation of scaffolds was also
      studied by monitoring their morphological changes, weight losses and decreases in
      average molecular weight of fiber matrix polymers.

PMID- 22592966
TI  - Who participates in a randomized trial of mindfulness-based stress reduction
      (MBSR) after breast cancer? A study of factors associated with enrollment among
      Danish breast cancer patients.
AB  - BACKGROUND: Discussion regarding the necessity to identify patients with both the
      need and motivation for psychosocial intervention is ongoing. Evidence for an
      effect of mindfulness-based interventions among cancer patients is based on few
      studies with no systematic enrollment. METHODS: We used Danish population-based
      registries and clinical databases to determine differences in demographics,
      breast cancer and co-morbidity among 1208 women eligible for a randomized
      controlled trial (www.clinicaltrials.gov identifier: NCT00990977) of mindfulness
      based stress reduction MBSR. RESULTS: Participants (N = 336) were found to be
      younger (p < 0.001) and have a less recent diagnosis at invitation than decliners
      (N = 872; p < 0.001). After adjustment for age and time since diagnosis at
      invitation, a statistically significant difference was also found between the two
      groups in use of psychologist sessions (p < 0.05), whereas neither breast cancer
      variables nor co-morbidity was significantly different. Self-reported data
      obtained by use of validated psychometric scales from 169 decliners and 336 women
      who agreed to enroll in the trial showed statistically significant differences in
      level of education, distress, anxiety, depression, well being and symptom burden.
      No differences were observed with regard to marital status, children living at
      home, affiliation to the work market, psychiatric caseness or any lifestyle
      measure. CONCLUSION: Our findings indicate that participants are younger, have a
      less recent diagnosis and have a higher level of education than those who refuse.
      This should be taken into account in designing and evaluating trials of
      psychosocial interventions and in planning mindfulness-based interventions.

PMID- 22592967
TI  - Helical self-assembly and co-assembly of fluorinated, preorganized discotics.
AB  - The synthesis and self-assembly properties of a fluorinated C(3)-symmetrical 3,3'
      bis(acylamino)-2,2'-bipyridine discotic (1) in the mesophase and in solution are
      described. First, 3,4,5-tris-(1H,1H,2H,2H,3H,3H-perfluoroundecyl-1-oxy)benzoyl
      chloride was coupled to mono-t-BOC protected 2,2'-bipyridine-3,3'-diamine to
      afford after deprotection the corresponding fluorinated aromatic amine on a
      multigram scale. Then, three-fold reaction of this amine with trimesyl chloride
      yielded the target C(3)-symmetrical fluorinated disc. The latter displayed
      columnar liquid crystallinity over a temperature range of more than 350 K in
      which helical rectangular and hexagonal columnar mesophases were detected by X
      ray diffraction measurements. (1)H-NMR spectroscopy showed a preorganized
      structure due to strong intramolecular hydrogen bonding between the amide N-H's
      and bipyridine nitrogen atoms, even in the presence of a large excess of
      hexafluoroisopropanol. This preorganized structure allows the formation of
      helical self-assemblies in fluorinated solvents, as was established using UV-Vis
      spectroscopy. The fluorinated disc and two chiral hydrocarbon analogues (a C(3)
      symmetrical and a desymmetrized disc) were mixed in a 1:10 v:v mixture of
      methoxynonafluorobutane (MNFB) and 1,1,2-trichloro-1,2,2-trifluoroethane (Freon
      113). Importantly, the C(3)-symmetrical hydrocarbon disc dissolves only in the
      presence of fluorinated disc in the latter solvent mixture, proving a mutual
      interaction. CD spectroscopy performed on these mixtures points to a preference
      for alternating self-assemblies of fluorinated and chiral hydrocarbon discotics.

PMID- 22592968
TI  - Synthesis, cytotoxic properties and tubulin polymerization inhibitory activity of
      novel 2-pyrazoline derivatives.
AB  - A series of novel 1-(3',4',5'-trimethoxybenzoyl)-3,5-diarylpyrazoline derivatives
      were synthesized and evaluated for their cytotoxic properties on different cancer
      cell lines and tubulin polymerization inhibitory activity. Compounds 6d and 6e
      exhibited remarkable cytotoxic activity against different cancer cell lines with
      good tubulin polymerization inhibitory activity. Compound 6d exhibited moderate
      selectivity toward renal cancer and breast cancer subpanels with selectivity
      ratios of 3.06 and 5.11, respectively, at the cytostatic activity (TGI) level.
      Compounds 6e and 6d achieved good tubulin polymerization inhibitory activity with
      IC(50) values of 17 and 40 uM, respectively. The photomicrographs made for
      compounds 6d and 6e on cellular microtubules indicated that the cytotoxicity of
      these compounds can be attributed to their ability to interfere with microtubule
      assembly. Molecular modeling studies involving compound 6e with the colchicine
      binding site of alpha,beta-tubulin revealed hydrogen-bonding and hydrophobic
      interactions with several amino acids in the colchicine binding site of beta
      tubulin.

PMID- 22592969
TI  - Observations during development of an internal medicine residency training
      program in cardiovascular limited ultrasound examination.
AB  - BACKGROUND: Despite the future potential of using ultrasound stethoscopes to
      augment the bedside cardiac physical, few data exist on a general cardiovascular
      imaging protocol that can be taught to physicians on a perpetual basis as a
      curriculum in graduate medical education. METHODS: During the past decade, we
      developed and integrated a cardiovascular limited ultrasound training program
      within the confines of an internal medicine residency. The evidence-based
      rationale for the exam, the teaching methods, and curriculum are delineated, and
      subsequent observations regarding program requirements, proficiency, and academic
      outcomes are explored. Analysis of variance and linear regression assessed for
      relationships between academic scores, chief resident selection, and gender to
      proficiency in ultrasound. RESULTS: A brief, 5-minute cardiovascular limited
      ultrasound exam (CLUE) was taught using both didactic and bedside methods, and
      practiced primarily within the cardiology consult, outpatient clinic, and
      intensive care rotations. Program costs were minimized by employing readily
      available institutional resources. After a 2-year lead-in training phase, the
      subsequent 4 years of senior resident performance (n = 41 residents) showed an
      81% pass rate in CLUE competency. Resident ultrasound performance did not relate
      to academic scores (r = 0.05, P = 0.75), chief resident selection, nor gender.
      Observations regarding resident pitfalls in CLUE practice and increased
      participation in extracurricular research are described. CONCLUSIONS: We report
      our initial experience in developing and implementing a training program for
      bedside cardiovascular ultrasound examination that employed evidence-based
      techniques, set proficiency goals, and assessed resident performance. It may be
      feasible to teach future internist-hospitalists the technique of bedside
      ultrasound during residency.

PMID- 22592970
TI  - A new semi-automated method for fetal volume measurements with three-dimensional
      ultrasound: preliminary results.
AB  - OBJECTIVE: Complications in pregnancy are suggested to be the result of
      intrauterine conditions in the first trimester of pregnancy. Three-dimensional
      ultrasound volume measurements might give more information, compared with two
      dimensional measurements. Commonly available methods for volume measurements are
      not suited for daily practice. This is a report of preliminary results of a
      promising, more practical semi-automated method for volume calculations with
      three-dimensional ultrasound. METHOD: Volume datasets of 16 objects (10.2-41.5
      cm(3) ) were obtained. Euclidean shortening flow and Perona and Malik were used
      as image enhancement techniques. The image gradient was calculated. The points of
      interest were detected by the iso-intensity and the edge-detection technique.
      Volume measurements with Volume Computer-aided AnaLysis (VOCAL) are used as a
      reference. A volume dataset of a first trimester fetus was acquired to test this
      method in vivo. RESULTS: The mathematical calculations with iso-intensity (Perona
      and Malik: average= -1.57 cm(3) , SD=4.05; and Euclidean shortening flow:
      average= -1.38 cm(3) , SD=2.47) showed results comparable with the VOCAL method
      (average= +1.28 cm(3) , SD=2.07). We also succeeded in detecting all voxels in
      the whole contour of a 12-week fetus. CONCLUSION: Mathematical volume
      calculations are possible with the semi-automated method. We were able to apply
      this new method on a first trimester fetus. This new method is promising for
      future use in the daily practice.

PMID- 22592971
TI  - Participation in unprofessional behaviors among hospitalists: a multicenter
      study.
AB  - BACKGROUND: Unprofessional behaviors undermine the hospital learning environment
      and quality of patient care. OBJECTIVE: To quantify perceptions of, and
      participation in, unprofessional behaviors among hospitalists. DESIGN:
      Observational survey study. SETTING: Three academic health centers. SUBJECTS:
      Hospitalists. MEASUREMENTS: Observation, participation in, and perceptions of
      unprofessional behaviors. RESULTS: Response rate was 76% (77/101). Nearly all
      behaviors were perceived as unprofessional ("unprofessional" or "somewhat
      unprofessional" on the Likert scale). Participation in egregious behaviors (ie,
      falsifying records) was low (<5%). The most frequent behaviors reported were
      having personal conversations in patient corridors (67.1%), ordering a test as
      "urgent" to expedite care (62.3%), and making fun of other physicians (40.3%).
      Four factors accounted for 76% of survey variance: (1) making fun of others; (2)
      learning environment (eg, texting during conferences); (3) workload management
      (eg, celebrating a blocked-admission); and (4) time pressure (eg, signing out
      work early). Hospitalists with less clinical time (<50% full-time equivalents
      [FTE]) were more likely to report making fun of others (beta = 0.94 [95% CI 0.32
      1.56], P = 0.004). Younger hospitalists (beta = 0.87 [95% CI 0.07-1.67], P =
      0.034) and those with administrative time (beta = 0.61 [95% CI 0.11-1.10], P =
      0.017) were more likely to report participating in workload management behaviors.
      Hospitalists who work night shifts were more likely to report participating in
      time-pressure behaviors (beta = 0.67 [95% CI 0.17-1.17], P = 0.010). Workload
      management and learning environment varied by site. CONCLUSION: While hospitalist
      participation in unprofessional behaviors is low, job characteristics (clinical,
      administrative, nights), age, and site were associated with different types of
      unprofessional behavior that may affect the learning environment and patient
      care.

PMID- 22592972
TI  - Studies of Mg2+/Ca2+ complexes of naturally occurring dinucleotides:
      potentiometric titrations, NMR, and molecular dynamics.
AB  - Dinucleotides (Np(n)N'; N and N' are A, U, G, or C, n = 2-7) are naturally
      occurring physiologically active compounds. Despite the interest in
      dinucleotides, the composition of their complexes with metal ions as well as
      their conformations and species distribution in living systems are understudied.
      Therefore, we investigated a series of Mg(2+) and Ca(2+) complexes of Np(n)N's.
      Potentiometric titrations indicated that a longer dinucleotide polyphosphate (N
      is A or G, n = 3-5) linker yields more stable complexes (e.g., log K of 2.70,
      3.27, and 3.73 for Ap(n)A-Mg(2+), n = 3, 4, 5, respectively). The base (A or G)
      or ion (Mg(2+) or Ca(2+)) has a minor effect on K(M)(ML) values. In a
      physiological medium, the longer Ap(n)As (n = 4, 5) are predicted to occur mostly
      as the Mg(2+)/Ca(2+) complexes. (31)P NMR monitored titrations of Np(n)N's with
      Mg(2+)/Ca(2+) ions showed that the middle phosphates of the dinucleotides
      coordinate with Mg(2+)/Ca(2+). Multidimensional potential of mean force (PMF)
      molecular dynamics (MD) simulations suggest that Ap(2)A and Ap(4)A coordinate
      Mg(2+) and Ca(2+) ions in both inner-sphere and outer-sphere modes. The PMF MD
      simulations additionally provide a detailed picture of the possible coordination
      sites, as well as the cation binding process. Moreover, both NMR and MD
      simulations showed that the conformation of the nucleoside moieties in Np(n)N'
      Mg(2+)/Ca(2+) complexes remains the same as that of free mononucleotides.

PMID- 22592973
TI  - Synthesis and biological evaluation of andrographolide derivatives as potent anti
      HIV agents.
AB  - In an attempt to develop potent anti-HIV drugs, 20 andrographolide derivatives
      were designed, synthesized, and evaluated for their in vitro anti-HIV activity.
      The screening results revealed that five compounds showed potent anti-HIV
      activities with therapeutic indices (TI) above 10. The most promising compound 6f
      shows a significant TI close to 34.07, with the potency to be a new lead.

PMID- 22592974
TI  - New sources of retinoic acid synthesis revealed by live imaging of an Aldh1a2-GFP
      reporter fusion protein throughout zebrafish development.
AB  - BACKGROUND: Regulation of synthesis and turnover of retinoic acid (RA) is an
      important mechanism that controls the activity of RA signaling during vertebrate
      development. During embryonic patterning, the dynamic expression patterns of the
      aldh1a2 gene, which encodes a retinaldehyde dehydrogenase, provide the major
      source of RA, whereas the only other retinaldehyde dehydrogenase in teleosts,
      aldh1a3, is expressed later and locally restricted. Aldh1a2-mediated RA synthesis
      has been shown to also regulate adult cell fates, such as during heart and fin
      regeneration. However, only very few other sites of postembryonic RA synthesis in
      vertebrates are known. We generated transgenic lines in zebrafish by BAC
      recombineering that express a fusion protein of Aldh1a2 and green fluorescent
      protein (GFP) under the control of endogenous aldh1a2 regulatory sequences
      (aldh1a2:gfp). RESULTS: aldh1a2:gfp reports the complete endogenous expression
      pattern in embryos and rescues embryonic lethality in aldh1a2 mutants. We
      identify novel postembryonic sources of RA synthesis, including lateral line
      support cells, in kidney-derived organs that regulate calcium homeostasis, and in
      perichordal cells during vertebral development. CONCLUSIONS: The novel aldh1a2
      reporter line is driven by the complete set of regulatory sequences required for
      zebrafish development, reports novel sources of RA synthesis, and identifies the
      source of RA that promotes vertebral ossification.

PMID- 22592975
TI  - Investigation into the genotoxicity of water extracts from Hypoxis species and a
      commercially available Hypoxis preparation.
AB  - We performed an in vitro evaluation of the genotoxic potential of water extracts
      from four Hypoxis species (Hypoxis hemerocallidea, H. colchicifolia, H. rigidula,
      H. acuminata) and a commercial preparation thereof using the neutral red uptake
      (NRU) assay, the alkaline comet assay and the cytome assay in human hepatoma
      HepG2 cells. The relative cytotoxicity of these samples was established by
      determining their NI50 values (50% inhibition of NRU), and these results were
      used for dose-finding in genotoxicity tests. None of the tested extracts were
      identified as genotoxic in both the alkaline comet assay and cytome assay.

PMID- 22592976
TI  - Impact of in-hospital enteroviral polymerase chain reaction testing on the
      clinical management of children with meningitis.
AB  - BACKGROUND: Enteroviral meningitis is a common cause of meningitis in children
      which requires only supportive care. OBJECTIVE: To evaluate the impact of
      implementing an in-hospital enteroviral polymerase chain reaction (EVPCR) testing
      protocol on the clinical management of children with meningitis. DESIGN:
      Retrospective cohort study. POPULATION: Children <19 years old with meningitis.
      INTERVENTION: EVPCR testing differed by time period: send-out testing protocol
      from July 1, 2006-June 23, 2008 (pre-period) versus in-house testing protocol
      from June 24, 2008-June 30, 2010 (post-period). MEASUREMENTS: Test turnaround
      time, test utilization, length of stay, and duration of parenteral antibiotics.
      RESULTS: Of the 441 study patients, 216 (49%) presented during the post-period.
      Median age was 2.9 months (interquartile range, 1.5-96 months). Test turnaround
      time decreased with the in-house test (53 hours pre vs 13 hours post, P < 0.001),
      and test utilization increased (28% pre vs 62% post, P < 0.001). Among children
      with a positive EVPCR test, both length of stay (44 hours pre vs 28 hours post, P
      = 0.005) and duration of parenteral antibiotics (48 hours pre vs 36 hours post, P
      = 0.04) decreased in the post-period. No change in either of these outcomes was
      observed in children with meningitis and a negative EVPCR test. CONCLUSION: In
      house EVPCR testing reduced test turnaround time, increased test utilization, and
      reduced both length of stay and duration of parenteral antibiotics for children
      with a positive result. Clinicians caring for children with meningitis should
      have access to in-hospital EVPCR testing.

PMID- 22592977
TI  - Synthesis and spectral characterization of new bis(2-(pyrimidin-2
      yl)ethoxy)alkanes and their pharmacological activity.
AB  - The pyrimidine nucleus is an important component of nucleic acids (DNA and RNA)
      and vitamins (B(2)  and folic acid). It is evident from the literature that
      pyrimidine derivatives possess a wide spectrum of biological activities such as
      antioxidant, anticancer, antibacterial, and anti-inflammatory activities. On the
      basis of diverse biological activities, we attempted to synthesize a series of
      novel bis(2-(pyrimidin-2-yl)ethoxy)alkanes 5a-j in four steps with good yields. 2
      Chloropyrimidine (1) was reacted with diethyl malonate in the presence of sodium
      hydride in dry dimethyl formamide to yield the intermediate diethyl 2-(pyrimidin
      2-yl)malonate (2), which on further reaction with sodium chloride and dimethyl
      sulfoxide yielded ethyl 2-(pyrimidin-2-yl)ethanoate (3). Reduction with sodium
      borohydride (NaBH(4) ) resulted in the formation of 2-(pyrimidin-2-yl)ethanol
      (4). This was further reacted with various dibromoalkanes to obtain the title
      compounds 5a-j. In this current study, we evaluated the antioxidant properties of
      the title compounds using four in vitro test systems: the 2,2-diphenyl-2
      picrylhydrazyl radical-, superoxide radical-, and hydroxyl radical-scavenging
      assays, and the anti-lipid peroxidation activity test. The title compounds showed
      promising antioxidant activity when compared to butylated hydroxytoluene. The
      potency of their antioxidant activity was mainly influenced by the alkyl fragment
      attached to 2-(pyrimidin-2-yl)ethanol. The ethyl and butyl fragments linked to
      oxygen led to increased antioxidant activity of the title compounds (i.e., 5b and
      5d) in all our in vitro assays.

PMID- 22592978
TI  - Effects of hepatocyte growth factor overexpressed bone marrow-derived mesenchymal
      stem cells on prevention from left ventricular remodelling and functional
      improvement in infarcted rat hearts.
AB  - Bone marrow-derived mesenchymal stem cells (BM-MSCs ) transplantation has been
      reported to be a promising therapy for myocardial infarction (MI). However, low
      survival rate of BM-MSCs in infarcted heart is one of the major limitations for
      the perspective clinical application. In this study, we aimed to investigate the
      effect of hepatocyte growth factor (HGF) on left ventricular function improvement
      of HGF gene-modified BM-MSCs (HGF-MSCs) after its delivery into the infarcted rat
      hearts. BM-MSCs were isolated with fibroblast-like morphology and expressed
      CD44+CD29+CD90+/CD34-CD45-CD31-CD11a. After 5-azacytidine induction in vitro, 20%
      30% of the cells were positively stained for desmin, cardiac-specific cardiac
      troponin I and connexin-43. Histological staining revealed that 2 weeks after MI
      is an optimal time point with decreased neutrophil infiltration and increased
      vascular number. Minimal infarct size and best haemodynamic analysis were also
      observed after cell injection at 2 weeks compared with that of 1 h, 1 week or 4
      weeks. Echocardiogram confirmed that transplantation with HGF-MSCs significantly
      improved left ventricular function compared with other groups in rat MI models.
      MSCs and HGF-MSCslabelled with DAPI were detected 4 weeks after MI in the
      infarcted area. Decreased infarcted scar area and increased angiogenesis
      formation could be found in HGF-MSCs group than in other groups as demonstrated
      by hematoxylin and eosin (H&E) staining and factor VIII staining. These results
      indicate that HGF-MSCs transplantation could enhance the contractile function and
      attenuate left ventricular remodelling efficiently in rats with MI.

PMID- 22592979
TI  - Annual Drosophila Research Conference, 2012.

PMID- 22592980
TI  - The evolution of dynamin to regulate clathrin-mediated endocytosis: speculations
      on the evolutionarily late appearance of dynamin relative to clathrin-mediated
      endocytosis.
AB  - Whereas clathrin-mediated endocytosis (CME) exists in all eukaryotic cells, we
      first detect classical dynamin in Ichthyosporid, a single-cell, metazoan
      precursor. Based on a key functional residue in its pleckstrin homology domain,
      we speculate that the evolution of metazoan dynamin coincided with the
      specialized need for regulated CME during neurotransmission.

PMID- 22592981
TI  - Two steps forward--one step back: advances in affinity purification mass
      spectrometry of macromolecular complexes.
AB  - Cellular functions are defined by the dynamic interactions of proteins within
      macromolecular networks. Deciphering these complex interplays is the key to
      getting a comprehensive picture of cellular behavior and to understanding
      biological systems, from a simple bacterial cell to highly regulated neuronal
      cells or cancerous tissue. In the last decade, affinity purification (AP) coupled
      to mass spectrometry has emerged as a powerful tool to comprehensively study
      interaction networks and their macromolecular assemblies. This review discusses
      recent advances in AP approaches, from cell lysis to the importance of sample
      preparation and the choice of AP matrix as well as the development of different
      epitope tags and strategies to study dynamic interactions, with an emphasis on
      RNA-protein interaction networks.

PMID- 22592982
TI  - Detection of melamine in infant formula and grain powder by surface-assisted
      laser desorption/ionization mass spectrometry.
AB  - We have developed a method for the determination of melamine (MEL), ammeline
      (AMN), and ammelide (AMD) by surface-assisted laser desorption/ionization mass
      spectrometry (SALDI-MS) using gold nanoparticles (Au NPs). The major peaks for
      MEL, AMN, and AMD at m/z 127.07, 128.05, and 129.04 are assigned to the [MEL +
      H](+), [AMN + H](+), and [AMD + H](+) ions. Because the three tested compounds
      adsorb weakly onto the surfaces of the Au NPs through Au-N bonding, they can be
      easily concentrated from complex samples by applying a simple
      trapping/centrifugation process. The SALDI-MS method provides limits of detection
      of 5, 10, and 300 nM for MEL, AMN, and AMD, respectively, at a signal-to-noise
      ratio of 3. The signal variation for 150-shot average spectra of the three
      analytes within the same spot was 15%, and the batch-to-batch variation was 20%.
      We have validated the practicality of this approach by the analysis of these
      three analytes in infant formula and grain powder. This simple and rapid SALDI-MS
      approach holds great potential for screening of MEL in foods.

PMID- 22592983
TI  - Investigation of absolute and relative response for three different liquid
      chromatography/tandem mass spectrometry systems; the impact of ionization and
      detection saturation.
AB  - RATIONALE: The investigations in this article were triggered by two observations
      in the laboratory; for some liquid chromatography/tandem mass spectrometry
      (LC/MS/MS) systems it was possible to obtain linear calibration curves for
      extreme concentration ranges and for some systems seemingly linear calibration
      curves gave good accuracy at low concentrations only when using a quadratic
      regression function. METHODS: The absolute and relative responses were tested for
      three different LC/MS/MS systems by injecting solutions of a model compound and a
      stable isotope labeled internal standard. The analyte concentration range for the
      solutions was 0.00391 to 500 MUM (128,000*), giving overload of the
      chromatographic column at the highest concentrations. The stable isotope labeled
      internal standard concentration was 0.667 MUM in all samples. RESULTS: The
      absolute response per concentration unit decreased rapidly as higher
      concentrations were injected. The relative response, the ratio for the analyte
      peak area to the internal standard peak area, per concentration unit was
      calculated. For system 1, the ionization process was found to limit the response
      and the relative response per concentration unit was constant. For systems 2 and
      3, the ion detection process was the limiting factor resulting in decreasing
      relative response at increasing concentrations. CONCLUSIONS: For systems behaving
      like system 1, simple linear regression can be used for any concentration range
      while, for systems behaving like systems 2 and 3, non-linear regression is
      recommended for all concentration ranges. Another consequence is that the
      ionization capacity limited systems will be insensitive to matrix ion suppression
      when an ideal internal standard is used while the detection capacity limited
      systems are at risk of giving erroneous results at high concentrations if the
      matrix ion suppression varies for different samples in a run.

PMID- 22592984
TI  - Isomerization of cannabidiol and Delta9-tetrahydrocannabinol during positive
      electrospray ionization. In-source hydrogen/deuterium exchange experiments by
      flow injection hybrid quadrupole-time-of-flight mass spectrometry.
AB  - RATIONALE: Liquid chromatography/tandem mass spectrometry (LC/MS/MS) is
      frequently used for analysis of cannabinoids in drug abuse control. Despite
      differences in structure, the isomers Delta(9) -tetrahydrocannabinol (THC) and
      cannabidiol (CBD) provide identical fragment spectra after positive electrospray
      ionization (ESI). For elucidation of the reason, hydrogen/deuterium (H/D)
      exchange experiments were performed. METHODS: Solutions of THC and CBD in D(2)
      O/acetonitrile (50:50, v/v) were flow-injected into acetonitrile as the mobile
      phase and measured by hybrid quadrupole-time-of-flight mass spectrometry (FI-QTOF
      MS) in targeted MS/MS mode. The MS and collision-induced dissociation (CID)
      spectra at 10, 20 and 40 eV were interpreted with respect to number and position
      of exchanged hydrogen atoms. For comparison the same measurements were preformed
      in H(2) O, after addition of 0.5% formic acid and with negative ESI. RESULTS:
      Depending on injected volume and position in the response curve, up to 7 or 8
      hydrogen atoms were exchanged by deuterium in THC or CBD. Positive ESI CID
      spectra were available for precursors with up to 4 exchanged D-atoms and showed
      that besides the OH groups also an H/D exchange at carbon atoms of the non
      aromatic part of the molecules occurred for both THC and CBD. After negative ESI,
      no H/D exchange in addition to the OH groups and different CID spectra of both
      substances was found. CONCLUSIONS: Injection of the investigated substances in
      D(2) O and measurement by FI-QTOF-MS proved to be an efficient way to perform H/D
      exchange experiments. The results were interpreted as an acid-catalyzed in-source
      equilibration between THC and CBD leading to the same precursor ions and to an
      H/D exchange in the methyl groups under the increased acidic conditions in the
      positive ESI droplets. Therefore, in positive LC/ESI-MS/MS, peak identification
      by CID spectra or by abundance ratio of multiple reaction monitoring (MRM)
      transitions is not sufficient for unambiguous discrimination between THC and CBD
      and must be supported by retention time or other experimental evidence.

PMID- 22592985
TI  - Electrochemistry/liquid chromatography/mass spectrometry to demonstrate
      irreversible binding of the skin allergen p-phenylenediamine to proteins.
AB  - RATIONALE: para-Phenylenediamine (PPD) is a potent and well-known allergen, which
      is commonly used in hair or fur dyes and can cause severe allergic contact
      dermatitis. In this work, the skin-sensitizing potential of PPD with respect to
      the conjugation of proteins was evaluated using an approach without animal
      testing. METHODS: Electrochemistry (EC) coupled offline to liquid chromatography
      (LC) and electrospray ionization mass spectrometry (ESI-MS) was employed to
      convert the pre-hapten PPD into its reactive hapten analogs. A previous study had
      already shown that this purely instrumental method is suitable for accelerating
      and simulating the various oxidation processes, which PPD may undergo, and that
      the emerging products are prone to react with soft thiol groups of small
      nucleophiles like glutathione and cysteine. RESULTS: This investigation was
      extended by successfully demonstrating adduct formation between EC-generated PPD
      oxidation products and the three proteins beta-lactoglobulin A (beta-LGA), human
      serum albumin and human hemoglobin. A tryptic digest of modified beta-LGA
      provided evidence for irreversible protein binding of monomeric PPD, a PPD dimer
      and the PPD trimer known as Bandrowski's Base. It was shown that the main
      oxidation product p-phenylene quinone diimine, and the reactive oligomerized
      species, primarily attack the free thiol function of proteins rather than other
      nucleophilic amino acid residues. CONCLUSIONS: The pre-hapten PPD was efficiently
      activated upon EC oxidation and the resulting species were further reacted with
      different proteins leading to diverse hapten-protein complexes. Thereby, problems
      related to the complex matrix present in conventional in vitro or in vivo methods
      could effectively be avoided.

PMID- 22592987
TI  - A simplified method for busulfan monitoring using dried blood spot in combination
      with liquid chromatography/tandem mass spectrometry.
AB  - RATIONALE: Busulfan (Bu) is an important component of the myeloablative
      conditioning regimen prior to hematopoietic stem cell transplantation (HSCT)
      especially in children. Intravenously administered Bu exhibits a therapeutic
      window phenomenon requiring therapeutic drug monitoring. Analytical methods
      developed for Bu routine monitoring were aimed at using low volumes of biological
      fluids and development of simple procedures to facilitate the dosage adjustment.
      In this report, we describe a simple, rapid method for Bu measurement using dried
      blood spots (DBS) from only 5 MUL of whole blood. METHODS: Bu extracted from DBS
      with methanol was measured by high-performance liquid chromatography with
      electrospray ionization and tandem mass spectrometry in multiple reaction
      monitoring mode using D8-Bu as an internal standard. The method was in-house
      validated evaluating trueness, repeatability, within-laboratory reproducibility,
      specificity and the lower limit of quantification (LLOQ). RESULTS: The method was
      linear in the calibration range of 100-2000 ng mL(-1) (r(2)>0.99) encompassing
      the therapeutic concentrations of Bu. A good trueness (<14%), precision (<10%),
      and recovery (100%) were observed during validation of the method with quality
      controls of 300, 600 and 1400 ng mL(-1). The LLOQ was determined as 50 ng mL(-1)
      and no matrix or carryover effects were observed. The validated method was
      applied to measure Bu levels in four children receiving infusion of Bu prior to
      HSCT. A good correlation was observed between the Bu levels measured by DBS and
      dried plasma spot (DPS) (r(2) =0.96) and between DPS and the GC/MS method (r(2)
      =0.92). Bu was found to be stable in DBS up to 6 h at room temperature and for 24
      h at 4  degrees C. CONCLUSIONS: The new DBS method facilitates earlier dosage
      adjustment during Bu therapy by its specific and simple procedure using 5 MUL of
      whole blood.

PMID- 22592986
TI  - Analysis of plasma nucleotides in rat by micellar electrokinetic capillary
      chromatography/electrospray ionization mass spectrometry.
AB  - RATIONALE: The aim of this study was to establish a simultaneous quantitative
      analysis method of nine endogenous nucleotides in rat plasma using micellar
      electrokinetic capillary chromatography/electrospray ionization mass spectrometry
      (MEKC/ESI-MS). METHODS: To select the optimum conditions for separation of the
      nucleotides, various pH, concentrations of running buffers and surfactants were
      tested. Ammonium acetate (20 mM) containing the surfactant
      dodecyltrimethylammonium bromide (2 mM, pH 3.5) was selected as the micellar
      running buffer. The plasma samples were prepared by precipitating the proteins
      with 2 mM EDTA in 60% ethanol. The samples were analyzed using capillary
      electrophoresis (CE)/MS and selected ion monitoring (SIM) mode with positive
      ionization. CE was performed using a silica capillary column in reversed polarity
      mode. RESULTS: The limits of detection (LODs) and limits of quantification (LOQs)
      of the nucleotides ranged from 0.05-5 and 2.0-20 MUM, respectively. The
      calibration curves were linear (R(2) >0.99) for all analytes, and the accuracy
      and precision were within +/-15%. The developed method was applied to the
      analysis of nucleotides in rat plasma that was collected after oral
      administration of acetaminophen (1000 mg/kg/day) to evaluate the changes in
      plasma nucleotide levels under hepatotoxic conditions. CONCLUSIONS: Decreased
      level of GTP and increased level of cytosine nucleotides were found to be
      associated with liver toxicity, which led to the conclusion that liver toxicity
      is closely related to changes in nucleotide levels in plasma.

PMID- 22592988
TI  - Active capillary plasma source for ambient mass spectrometry.
AB  - RATIONALE: Imaging mass spectrometry with high spatial resolution has become a
      rapidly developing area of mass spectrometric research. Many scientific and
      industrial problems deal with mass spectrometric analysis at ambient pressures.
      This requires efficient transport and ionization of small amounts of substance.
      METHODS: An active sampling capillary based on a dielectric barrier discharge was
      constructed for ambient mass spectrometry. The capillary serves as an ionization
      source as well as an atmospheric interface of the mass spectrometer. The analyzed
      samples are transported through the sampling capillary due to the pressure
      difference between the atmospheric environment and the vacuum in the mass
      spectrometer. Ionization of the transported samples is provided by a low
      temperature dielectric barrier discharge. This active capillary was shown to work
      in a robust fashion for ionizing both gas-phase and laser-ablated solid-phase
      samples. RESULTS: The geometry of the electrodes was found to play a crucial role
      in ionization efficiency. The capillary was optimized in order to perform surface
      analysis of solid samples. Sensitivity tests were carried out to characterize
      different active capillary constructions. The sensitivity of the constructed
      active capillary was 0.1 ppb (relative concentration of a gaseous sample in
      ambient air). The active capillary was able to detect samples evaporated from a
      solid surface. With the active capillary source, it was possible to detect
      anthracene traces evaporated from a surface located 3 cm from the capillary
      inlet. CONCLUSIONS: A plasma-based active capillary ionization source was
      constructed. This concept of an active sample inlet should broaden the range of
      applications of ambient mass spectrometry.

PMID- 22592989
TI  - Electrochemistry/mass spectrometry as a tool in the investigation of the potent
      skin sensitizer p-phenylenediamine and its reactivity toward nucleophiles.
AB  - RATIONALE: Although para-phenylenediamine (PPD) is known to cause severe allergic
      contact dermatitis in consequence of autoxidation and/or skin metabolism
      pathways, it is commonly utilized as an ingredient in permanent hair dyes. The
      aim of this work was to simultaneously accelerate the autoxidation process and to
      simulate the metabolic activation of PPD using a purely instrumental system.
      METHODS: Electrochemistry (EC) in combination with electrospray ionization mass
      spectrometry (ESI-MS) was used in this study to assess the skin-sensitizing
      potential of PPD. Online and offline coupled EC/ESI-MS experiments were carried
      out and the emerging oxidation products were investigated. In a second approach,
      these primary species were allowed to react with the nucleophiles glutathione
      (GSH), cysteine (Cys), potassium cyanide (KCN) and lysine (Lys) in order to
      evaluate their reactivity. RESULTS: The reactive p-phenylene quinone diimine
      (PPQD), which can form upon autoxidation and/or skin metabolism of PPD, was
      effectively generated in a simple EC cell next to further oxidation products,
      including the trimeric product Bandrowski's Base (BB). Conjugation with GSH and
      Cys was successfully proven, but no adducts with KCN or Lys were observed.
      Furthermore, the application of different concentration ratios between PPD and
      nucleophile was shown to play a crucial role concerning the type of oxidation
      products and adducts being formed. CONCLUSIONS: It was found that EC/MS is a well
      suited approach for the targeted generation of reactive haptens such as PPQD
      while avoiding detection problems due to the complexity of matrices encountered
      when conducting conventional in vitro or in vivo experiments.

PMID- 22592990
TI  - Systematic evaluation of the root cause of non-linearity in liquid
      chromatography/tandem mass spectrometry bioanalytical assays and strategy to
      predict and extend the linear standard curve range.
AB  - RATIONALE: The linear range of a liquid chromatography/tandem mass spectrometry
      (LC/MS/MS) bioanalytical assay is typically about three orders of magnitude. A
      broader standard curve range is favored since it can significantly reduce the
      time, labor and potential errors related to sample dilution - one of the
      bottlenecks in sample analysis. Using quadratic regression to fit the standard
      curve can, to a certain degree, extend the dynamic range. However, the use of a
      quadratic regression is controversial, particularly in regulated bioanalysis.
      METHODS: A number of compounds, with different physicochemical properties and
      ionization efficiencies, were evaluated to understand the cause of the non-linear
      behavior of the standard curve. RESULTS: The standard curve behavior is primarily
      associated with the absolute analyte response but not the analyte concentration,
      the properties of the analyte, or the nature of the matrix when a stable-isotope
      labeled internal standard (SIL-IS) is used. For all the test compounds, a non
      linear curve was observed when signals exceeded a certain response, which depends
      on the detector used in the mass spectrometer. With typical API4000 instruments
      used for the experiments, this critical response level was determined to be ~1
      E+6 counts per second (cps) and it was successfully used to predict the linear
      ranges for the test compounds. By simultaneously monitoring two selective
      reaction monitoring (SRM) channels of different intensity and using SIL-IS, a
      linear range of five orders of magnitude was achieved. CONCLUSIONS: In this work,
      the root cause of the non-linear behavior of the standard curve when using a SIL
      IS was investigated and identified. Based on the findings, an improved multiple
      SRM channels approach was proposed and successfully applied to obtain a linear
      dynamic range of five orders of magnitude for one test compound. This approach
      may work particularly well for LC/MS/MS bioanalytical assay of dried blood spot
      (DBS) samples, for which a direct dilution is cumbersome.

PMID- 22592991
TI  - A simple method for the removal of dissolved organic matter and delta15N analysis
      of NO3(-) from freshwater.
AB  - RATIONALE: Stable isotopes of nitrogen in nitrate (NO(3)(-)) are frequently used
      to identify nitrate sources and to study nitrogen (N) transformation processes,
      but the measurement methods available are generally rather labor intensive and/or
      costly, and dissolved organic matter (DOM) can interfere with the delta(15)N
      signature of nitrate. We therefore have developed a simple cleanup procedure for
      freshwater samples with low nitrate and high DOM concentrations. METHODS: Nitrate
      and DOM are extracted from a freeze-dried water sample by using a concentrated
      sodium hydroxide solution. By the subsequent addition of acetone, two liquid
      layers are formed, and nitrate migrates into the acetone while DOM remains in the
      concentrated NaOH solution, thus separating the nitrate from the DOM. For
      nitrogen isotope analysis, purified nitrate salts are combusted at 1030  degrees
      C to produce N(2) gas in an elemental analyzer (EA) coupled to an isotope ratio
      mass spectrometer (IRMS). RESULTS: With this novel technique up to 99% of DOM
      could be removed from river water and soil solutions. The method has been tested
      for sample amounts as small as 4 umol NO(3)(-) with a precision of <0.10/00
      (1SD). Nitrate standards are reproduced accurately without any blank correction.
      CONCLUSIONS: The benefits of this method are the lack of interferences derived
      from DOM on the delta(15)N signature and the ease of sample preparation.

PMID- 22592992
TI  - Study of a quadrupole ion trap with damping force by the two-point one block
      method.
AB  - RATIONALE: The capabilities and performances of a quadrupole ion trap under
      damping force based on collisional cooling is of particular importance in high
      resolution mass spectrometry and should be analyzed by Mathieu's differential
      solutions. These solutions describe the stability and instability of the ion's
      trajectories confined in quadrupole devices. One of the methods for solving
      Mathieu's differential equation is a two-point one block method. In this case,
      Mathieu's stability diagram, trapping parameters a(z) and q(z) and the secular
      frequency of the ion motion w(z), can be derived in a precise manner. The two
      point one block method (TPOBM) of Adams Moulton type is presented to study these
      parameters with and without the effect of damping force and compared to the 5th
      order Runge-Kutta method (RKM5). The simulated results show that the TPOBM is
      more accurate and 10 times faster than the RKM5. The physical properties of the
      confined ions in the r and z axes are illustrated and the fractional mass
      resolutions m/Deltam of the confined ions in the first stability region were
      analyzed by the RKM5 and the TPOBM. METHODS: The Lagrange interpolation
      polynomial was applied in the derivation of the proposed method. The proposed
      method will be utilized to obtain a series solution directly without reducing it
      to first order equations. RESULTS: The problem was tested with the ion
      trajectories in real time with and without the effect of damping force using
      constant step size. Numerical results from the two-point one block method have
      been compared with the fifth order Runge-Kutta method. CONCLUSIONS: The proposed
      two-point one block method has a potential application to solve complicated
      linear and nonlinear equations of the charged particle confinement in a
      quadrupole field especially in fine tuning accelerators, and, generally speaking,
      in physics of high energy.

PMID- 22592993
TI  - Multicomponent mixed dopant optimization for rapid screening of polycyclic
      aromatic hydrocarbons using ultra high performance liquid chromatography coupled
      to atmospheric pressure photoionization high-resolution mass spectrometry.
AB  - RATIONALE: To enhance the ionization efficiencies in atmospheric pressure
      photoionization mass spectrometry a dopant with favorable ionization energy such
      as chlorobenzene is typically used. These dopants are typically toxic and
      difficult to mix with water-soluble organic solvents. In order to achieve a more
      efficient and less toxic dopant, a multicomponent mixed dopant was explored.
      METHODS: A multicomponent mixed dopant for non-targeted rapid screening of
      polycyclic aromatic hydrocarbons (PAHs) was developed and optimized using ultra
      high performance liquid chromatography (UPLC) coupled to atmospheric pressure
      photoionization high-resolution mass spectrometry. Various single and
      multicomponent mixed dopants consisting of ethanol, chlorobenzene, bromobenzene,
      anisole and toluene were evaluated. RESULTS: Fourteen out of eighteen PAHs were
      successfully separated and detected at low pg/MUL levels within 5 min with high
      mass accuracy <=4 ppm. The optimal mixed multicomponent dopant consisted of
      ethanol/chlorobenzene/bromobenzene/anisole (98.975:0.1:0.9:0.025, v/v %) and it
      improved the limit of detection (LOD) by 2- to 10-fold for the tested PAHs
      compared to those obtained with pure chlorobenzene. CONCLUSIONS: A novel
      multicomponent dopant that contains 99% ethanol and 1% mixture of chlorobenzene,
      bromobenzene and anisole was found to be an effective dopant mixture to ionize
      PAHs. The developed UPLC multicomponent dopant assisted atmospheric pressure
      photoionization high-resolution mass spectrometry offered a rapid non targeted
      screening method for detecting the PAHs at low pg/MUL levels within a 5 min run
      time with high mass accuracy <=4 ppm.

PMID- 22592994
TI  - Simultaneous quantification of microcystins and nodularin in aerosol samples
      using high-performance liquid chromatography/negative electrospray ionization
      tandem mass spectrometry.
AB  - RATIONALE: Cyanobacteria are a small group of photosynthetic planktonic bacteria,
      producing a large group of strong hepatotoxins called microcystins (MCs). Many
      studies have been conducted to evaluate the presence of MCs and nodularin (NOD)
      in water or in marine organisms, but little research has been done on the
      atmospheric environment. Waterborne toxins can be found in the aerosol phase due
      to bubble-bursting processes. METHODS: The aim of this study was to obtain a
      sensitive method for the simultaneous determination of trace concentrations of
      individual cyanotoxins in aerosol samples, using liquid chromatography coupled
      with a triple quadrupole (HPLC/MS/MS). During method development improved
      electrospray ionization was found in negative ion mode. In contrast with other
      authors, we have developed a chromatographic separation using alkaline
      conditions, thus achieving good resolution, improved electrospray ionization and
      therefore better sensitivity. RESULTS: A sensitive analytical method was set up
      to simultaneously measure trace concentrations of cyanotoxins in aerosol samples
      in a single chromatographic analysis using the internal standard method. The
      limit of detection for all the toxins was determined to be between 1 fg/MUL (MC
      LA and LF) and 9 fg/MUL (NOD). CONCLUSIONS: The method was applied to ten aerosol
      samples from the Venice Lagoon. In these samples, trace concentrations of MC-LA
      ranging between 90 fg m(-3) and 706 fg m(-3), MC-LF between n.d. and 369 fg m(-3)
      and MC-LW between n.d. and 262 fg m(-3). This is the first study to quantify the
      cyanotoxins in Venetian aerosol samples using the HPLC/(-)ESI-MS/MS.

PMID- 22592995
TI  - Mitigation of signal suppression caused by the use of trifluoroacetic acid in
      liquid chromatography mobile phases during liquid chromatography/mass
      spectrometry analysis via post-column addition of ammonium hydroxide.
AB  - A method has been developed to reduce the mass spectrometric ion signal
      suppression associated with the use of TFA as an additive in LC mobile phases.
      Through post-column infusion of diluted NH(4)OH solution to LC eluents, the
      ammonium ion introduced causes the neutral analyte-TFA ion pair to dissociate
      which consequently releases the protonated analyte as free ions into the gas
      phase (through regular electrospray ionization mechanisms). An ion signal
      improvement from 1.2 to 20 times for a variety of compounds had been achieved
      through the application of this method. The molar ratios of NH(4)OH:TFA which
      result in a reduction of signal suppression were determined to be between 0.5:1
      and 50:1. In addition, it was shown that this NH(4)OH infusion method could
      reduce the level of doubly-charged species and the product ions formed via in
      source collision. The use of diluted NH(4)OH solution is favorable since it is
      compatible with mass spectrometry analysis, and it is applicable in both positive
      and negative-ion generation mode.

PMID- 22592997
TI  - Synthesis and bioevaluation of diphyllin glycosides as novel anticancer agents.
AB  - A series of diphyllin glycosides were synthesized from diphyllin by phase
      transfer catalysis glycosylation, deprotection, and etherification, and the
      structures were established by (1) H NMR, (13) C NMR, and HRMS. These glycosides
      were evaluated for their in vitro cytotoxicity against HCT-116, A549, and A549T
      cancer cell lines by MTT assay, and most of them were cytotoxic at submicromolar
      concentrations. They were also effective against the paclitaxel-resistant cell
      line A549T. The kDNA decatenation assay indicated that most of these compounds
      inhibited topoisomerase IIalpha-mediated kDNA decatenation. In addition, the in
      vitro tubulin polymerization study showed that compounds 5 and 6 had
      antimicrotubule activity with a paclitaxel-like mode of action. Taken together,
      these results suggest that these diphyllin glycosides act on both TopoII and
      tubulin.

PMID- 22593000
TI  - Computational structural analysis of protein interactions and networks.
AB  - Protein interactions have been at the focus of computational biology in recent
      years. In particular, interest has come from two different communities-
      structural and systems biology. Here, we will discuss key systems and structural
      biology methods that have been used for analysis and prediction of protein
      protein interactions and the insight these approaches have provided on the nature
      and organization of protein-protein interactions inside cells.

PMID- 22592999
TI  - Piperlongumine induces rapid depletion of the androgen receptor in human prostate
      cancer cells.
AB  - BACKGROUND: Androgen receptor (AR) signaling is regarded as the driving force in
      prostate carcinogenesis, and its modulation represents a logical target for
      prostate cancer (PC) prevention and treatment. Natural products are the most
      consistent source of small molecules for drug development. In this study, we
      investigate the functional impact of piperlongumine (PL), a naturally occurring
      alkaloid present in the Long pepper (Piper longum), on AR expression in PC cells
      and delineate its mechanism of action. METHODS: Expression and transcriptional
      activity of AR was examined by western blotting and luciferase reporter assay,
      respectively. CellTiter Blue assay was utilized to quantify cell proliferation.
      Reactive oxygen species (ROS) generation was examined by staining cells with a
      ROS indicator CM-H(2) DCFDA, followed by flow cytometry analysis. RESULTS: The
      results of our experiments demonstrate that PL rapidly reduces AR protein levels
      in PC cells via proteasome-mediated ROS-dependent mechanism. Moreover, PL
      effectively depletes a modified AR lacking the ligand-binding domain, shedding
      light on a new paradigm in the treatment approach to prostatic carcinoma that
      expresses mutated constitutively active AR. Importantly, PL effectively depletes
      AR in PC cells at low micromolar concentrations, while concurrently exerting a
      significant inhibitory effect on AR transcriptional activity and proliferation of
      PC cells. CONCLUSIONS: Our investigation demonstrates for the first time that PL
      induces rapid depletion of the AR in PC cells. As such, PL may afford novel
      opportunities for both prevention and treatment of prostatic malignancy.

PMID- 22593001
TI  - Inhibitory effect of luteolin on the odorant-induced cAMP level in HEK293 cells
      expressing the olfactory receptor.
AB  - Luteolin is a flavonoid in many fruits and vegetables. Although luteolin has
      important biological functions, including antioxidant, anti-inflammatory,
      antimicrobial, and neuroprotective activities, little is known about the
      functions of luteolin in the olfactory system. Various odorants can be detected
      and distinguished by using several molecular processes, including the binding of
      odorants to odorant receptors, activation of adenylyl cyclase (AC), changes of
      cyclic adenosine monophosphate (cAMP) and Ca(2+)  levels in olfactory sensory
      neurons, as well as changes in membrane potentials and the transmission of
      electric signals to the brain. Because AC-cAMP signal transduction plays a
      pivotal role in the olfactory system, we evaluated the effects of luteolin on the
      AC-cAMP pathway that had been stimulated by the odorant eugenol. We demonstrated
      that eugenol caused an upregulation of the cAMP level and the phosphorylation of
      phosphokinase A (PKA, a downstream target of cAMP) in human embryonic kidney 293
      (HEK293) cells expressing the murine eugenol receptor. This upregulation
      significantly decreased in the presence of luteolin, suggesting that luteolin
      inhibited the odorant-induced production of cAMP and affected the downstream
      phosphorylation of PKA.

PMID- 22592998
TI  - Astrocytic regulation of glutamate homeostasis in epilepsy.
AB  - Astrocytes play a critical role in regulation of extracellular neurotransmitter
      levels in the central nervous system. This function is particularly prominent for
      the excitatory amino acid glutamate, with estimates that 80-90% of extracellular
      glutamate uptake in brain is through astrocytic glutamate transporters. This
      uptake has significance both in regulation of the potential toxic accumulation of
      extracellular glutamate and in normal resupply of inhibitory and excitatory
      synapses with neurotransmitter. This resupply of neurotransmitter is accomplished
      by astroglial uptake of glutamate, transformation of glutamate to glutamine by
      the astrocytic enzyme glutamine synthetase (GS), and shuttling of glutamine back
      to excitatory and inhibitory neurons via specialized transporters. Once in
      neurons, glutamine is enzymatically converted back to glutamate, which is
      utilized for synaptic transmission, either directly, or following decarboxylation
      to gamma-aminobutyric acid. Many neurologic and psychiatric conditions,
      particularly epilepsy, are accompanied by the development of reactive gliosis, a
      pathology characterized by anatomical and biochemical plasticity in astrocytes,
      accompanied by proliferation of these cells. Among the biochemical changes
      evident in reactive astrocytes is a downregulation of several of the important
      regulators of the glutamine-glutamate cycle, including GS, and possibly also
      glutamate transporters. This downregulation may have significance in contributing
      both to the aberrant excitability and to the altered neuropathology
      characterizing epilepsy. In the present review, we provide an overview of the
      normal function of astrocytes in regulating extracellular glutamate homeostasis,
      neurotransmitter supply, and excitotoxicity. We further discuss the potential
      role reactive gliosis may play in the pathophysiology of epilepsy.

PMID- 22593002
TI  - Molecular genetic analysis of MSUD from India reveals mutations causing altered
      protein truncation affecting the C-termini of E1alpha and E1beta.
AB  - Maple Syrup Urine Disease is a rare metabolic disorder caused by reduced/absent
      activity of the branched chain alpha-Ketoacid dehydrogenase enzyme complex.
      Mutations in BCKDHA, BCKDHB, and DBT, that encode important subunits of the
      enzyme complex namely E1alpha, E1beta, and E2, are the primary cause for the
      disease. We have performed the first molecular genetic analysis of MSUD from
      India on nine patients exhibiting classical MSUD symptoms. BCKDHA and BCKDHB
      mutations were identified in four and five patients, respectively including seven
      novel mutations namely the BCKDHA c.1249delC, c.1312T>C, and c.1561T>A and the
      BCKDHB c.401T>A, c.548G>A, c.964A>G, and c.1065delT. The BCKDHB c.970C>T
      (p.R324X) mutation was shown to trigger nonsense mediated decay-based degradation
      of the transcript. Seven of the total 11 mutations resulted in perturbations in
      the E1alpha or E1beta C-termini either through altered termination or through an
      amino acid change; these are expected to result in disruption of E1 enzyme
      complex assembly. Our study has therefore revealed that BCKDHA and BCKDHB
      mutations might be primarily responsible for MSUD in the Indian population.

PMID- 22593003
TI  - Fluorescence in situ hybridization of three oncogenes on a leiomyoma.
AB  - Using fluorescence in situ hybridization technique, expression of three
      oncogenes, C-myc, RARa, and cyclin-D was tested on a uterine leiomyoma. C-myc and
      RARa were amplified in approximately 30% and 90% of the cells, respectively.
      Numerous small signals of C-myc were indicative of the presence of double
      minutes. Amplification of RARa is being reported for the first time in a
      leiomyoma. Cyclin-D was normal in diploid cells while it was highly amplified in
      polyploid cells. Low levels of amplified C-myc and cyclin-D cells seem to be the
      reason for this tumor to be benign, while RARa could not be effective without the
      association of some other gene such as PML. Information presented here are
      significant toward developing new curative strategies such as gene-specific drugs
      and molecular manipulation to stop the activity of cancer gene. Further study may
      elucidate that how fibroids grow and maintain their rare benign nature.

PMID- 22593004
TI  - ATP and noradrenaline activate CREB in astrocytes via noncanonical Ca(2+)  and
      cyclic AMP independent pathways.
AB  - In neurons, it is well established that CREB contributes to learning and memory
      by orchestrating the translation of experience into the activity-dependent (i.e.,
      driven by neurotransmitters) transcription of plasticity-related genes. The
      activity-dependent CREB-triggered transcription requires the concerted action of
      cyclic AMP/protein kinase A and Ca(2+) /calcineurin via the CREB-regulated
      transcription co-activator (CRTC). It is not known, however, whether a comparable
      molecular sequence occurs in astrocytes, despite the unquestionable contribution
      of these cells to brain plasticity. Here we sought to determine whether and how
      ATP and noradrenaline cause CREB-dependent transcription in rat cortical
      astrocyte cultures. Both transmitters induced CREB phosphorylation (Western
      Blots), CREB-dependent transcription (CRE-luciferase reporter assays), and the
      transcription of Bdnf, a canonical regulator of synaptic plasticity (quantitative
      RT-PCR). We indentified a Ca(2+) and diacylglycerol-independent protein kinase C
      at the uppermost position of the cascade leading to CREB-dependent transcription.
      Notably, CREB-dependent transcription was partially dependent on ERK1/2 and CRTC,
      but independent of cyclic AMP/protein kinase A or Ca(2+) /calcineurin. We
      conclude that ATP and noradrenaline activate CREB-dependent transcription in
      cortical astrocytes via an atypical protein kinase C. It is of relevance that the
      signaling involved be starkly different to the one described in neurons since
      there is no convergence of Ca(2+) and cyclic AMP-dependent pathways on CRTC,
      which, moreover, exerts a modulatory rather than a central role. Our data thus
      point to the existence of an alternative, non-neuronal, glia-based role of CREB
      in plasticity.

PMID- 22593005
TI  - Alpha methylacyl-CoA racemase (AMACR) in prostate adenocarcinomas from Japanese
      patients: is AMACR a "race"-dependent marker?
AB  - BACKGROUND: Alpha methylacyl-CoA racemase (AMACR) is a useful diagnostic marker
      for prostate adenocarcinoma. However, its usefulness has not been fully validated
      in Japanese patients. The aim of this study was to evaluate the diagnostic
      utility of AMACR in prostate needle biopsy examination in Japanese patients.
      METHODS: A total of 119 prospective consecutive prostate needle biopsy specimens
      (680 cores) obtained from Japanese patients were examined. Sixty patients had
      adenocarcinoma (adenocarcinoma, 160 cores; benign, 204 cores), 14 patients had
      high-grade prostatic intraepithelial neoplasia (HGPIN; 19 cores), and 45 patients
      did not have any neoplastic lesions (297 cores). AMACR expression was scored semi
      quantitatively as 0 (no expression), 1+ (partial and/or weak expression), or 2+
      (strong, circumferential expression). The number of positively stained glands was
      counted. RESULTS: 2+ AMACR expression was observed in 70.1% of adenocarcinoma
      cases and in 52.6% of HGPIN cases. Of the adenocarcinoma cases showing 2+ AMACR
      expression, 34.8% demonstrated a heterogeneous expression pattern, with 1-75% of
      AMACR-positive glands. Three hundred eighty-five of the benign glands with an
      adenocarcinoma component showed 2+ AMACR expression (35 cases, 94 cores). 2+
      AMACR expression was observed in 67 non-neoplastic benign glands (9 cases, 19
      cores). CONCLUSIONS: The sensitivity and specificity of AMACR for the diagnosis
      of prostate adenocarcinoma and benign glands in Japanese patients are lower than
      those previously reported in Western countries. Pathologists should be cautious
      while interpreting AMACR expression pattern in Japanese patients.

PMID- 22593006
TI  - Quantitative analysis of five kudinosides in the large-leaved Kudingcha and
      related species from the genus Ilex by UPLC-ELSD.
AB  - INTRODUCTION: The large-leaved Kudingcha from the genus Ilex, which is used as a
      traditional Chinese tea, contains several characteristic triterpenoid saponins
      that can be subjected to quality control evaluation. OBJECTIVE: To develop and
      validate a rapid method incorporating reverse-phase ultra-performance liquid
      chromatography coupled with evaporative light scattering detection (UPLC-ELSD)
      for the simultaneous determination of the five triterpenoid saponins kudinoside L
      (1), kudinoside C (2), kudinoside A(3), kudinoside F(4) and kudinoside D(5) in
      several species of the large-leaved Kudingcha from the genus Ilex and 'Yerba
      Mate' (Ilex paraguariensis). METHODOLOGY: The five compounds were separated using
      a water-acetonitrile mobile phase with a Waters Acquity BEH C(18)-column (100 *
      2.1 mm, 1.7 um). RESULTS: Separation took 13 min with detection and
      quantification limits ranging from 12.5 to 29.8 ng and 41.3 to 98.2 ng,
      respectively. The method was validated according to the regulatory guidelines
      with respect to precision, stability, repeatability and recovery. The
      triterpenoid saponins showed a good regression relationship (r(2) > 0.999) within
      the test ranges, and the recovery of the method was in the 95-105% range.
      CONCLUSION: The present method can be used successfully for the quality control
      of the large-leaved Kudingcha. The different Ilex species showed differences in
      distribution of the five triterpenoids. Ilex kudingcha, which makes up the major
      species of the large-leaved Kudingcha, contains the maximum amount of
      triterpenoid saponins.

PMID- 22593007
TI  - Protein interaction networks in medicine and disease.
AB  - The physical interaction of proteins is subject to intense investigation that has
      revealed that proteins are assembled into large densely connected networks. In
      this review, we will examine how signaling pathways can be combined to form
      higher order protein interaction networks. By using network graph theory, these
      interaction networks can be further analyzed for global organization, which has
      revealed unique aspects of the relationships between protein networks and complex
      biological phenotypes. Moreover, several studies have shown that the structure
      and dynamics of protein networks are disturbed in complex diseases such as cancer
      progression. These relationships suggest a novel paradigm for treatment of
      complex multigenic disease where the protein interaction network is the target of
      therapy more so than individual molecules within the network.

PMID- 22593008
TI  - E2F1-dependent pathways are involved in amonafide analogue 7-d-induced DNA
      damage, G2/M arrest, and apoptosis in p53-deficient K562 cells.
AB  - The E2F1 gene well known is its pivotal role in regulating the entry from G1 to S
      phase, while the salvage antitumoral pathway which implicates it, especially in
      the absence of p53, is not fully characterized. We therefore attempted to
      identify the up- and down-stream events involved in the activation of the E2F1
      dependent pro-apoptotic pathway. For this purpose, a amonafide analogue, 7-d (2
      (3-(2-(Dimethylamino)ethylamino)propyl)-6-(dodecylamino)-1H-benzo[de]isoquinoline
      1,3(2H)-dione) was screened, which exhibited high antitumor activity against p53
      deficient human Chronic Myelogenous Leukemia (CML) K562 cells. Analysis of flow
      cytometry and western blots of K562 cells treated with 7-d revealed an
      appreciable G2/M cycle arrest and apoptosis in a dose and time-dependent manner
      via p53-independent pathway. A striking increase in "Comet tail" formation and
      gamma-H2AX expression showed that DNA double strand breaks (DSB) were caused by 7
      d treatment. ATM/ATR signaling was reported to connect E2F1 induction with
      apoptosis in response to DNA damage. Indeed, 7-d-induced G2/M arrest and
      apoptosis were antagonized by ATM/ATR signaling inhibitor, Caffeine, which
      suggested that ATM/ATR signaling was activated by 7-d treatment. Furthermore, the
      increased expression of E2F1, p73, and Apaf-1 and p73 dissociation from HDM2 was
      induced by 7-d treatment, however, knockout of E2F1 expression reversed p73, Apaf
      1, and p21(Cip1/WAF1) expression, reactivated cell cycle progression, and
      inhibited 7-d-induced apoptosis. Altogether our results for the first time
      indicate that 7-d mediates its growth inhibitory effects on CML p53-deficient
      cells via the activation of an E2F1-dependent mitochondrial and cell cycle
      checkpoint signaling pathway which subsequently targets p73, Apaf-1, and
      p21(Cip1/WAF1).

PMID- 22593009
TI  - Validity of the Generalized Anxiety Disorder-7 scale in an acute psychiatric
      sample.
AB  - Generalized anxiety disorder (GAD) is one of the most prevalent psychiatric
      presentations; however, GAD has the lowest diagnostic reliability of the anxiety
      disorders and is poorly recognized in clinical practice. A more reliable
      assessment of GAD could lead to earlier detection and treatment of the disorder,
      which has an otherwise debilitating course and significant associated impairment.
      The 7-item GAD Scale (GAD-7) has shown promise as a measure with good clinical
      utility and strong psychometric properties in primary care and community settings
      but has yet to be assessed in acute psychiatric populations. This study examined
      the validity of the GAD-7 in a sample of 232 patients enrolled in a partial
      hospital programme. Patients completed a diagnostic interview and a battery of
      self-report measures before and after treatment. Findings suggest that the GAD-7
      has good internal consistency and good convergent validity with worry, anxiety,
      depression and stress, and the measure was sensitive to change over the course of
      a short intensive cognitive-behavioural therapy partial hospital programme.
      However, the confirmatory analysis failed to support the hypothesized
      unidimensional factor structure; and although the GAD-7 demonstrated good
      sensitivity (.83), specificity was poor (.46) in identifying patients with GAD.
      Overall, the GAD-7 appears to be a valid measure of generalized anxiety symptoms
      in this sample, on the basis of good internal consistency, convergent validity
      and sensitivity to change, but does not perform well as a screener for GAD. KEY
      PRACTITIONER MESSAGE: The GAD-7 Scale is an easy-to-score, self-report measure of
      core generalized anxiety disorder symptoms. The GAD-7 Scale has good internal
      consistency and convergent validity with depression, anxiety, stress and worry,
      and is sensitive to change. The GAD-7 Scale appears to be a good measure of
      generalized anxiety symptoms in an acute psychiatric sample. The GAD-7 Scale does
      not perform well as a screener for GAD and should not be used to identify cases
      of GAD in acute psychiatric samples.

PMID- 22593010
TI  - The CpG island shore of the GLT-1 gene acts as a methylation-sensitive enhancer.
AB  - Astrocytic lineage commitment and brain region-dependent specialization of glia
      are partly ascribed to epigenetic processes. Clearance of glutamate is an
      essential task, which astrocytes assume in a temporal-spatial fashion by distinct
      glutamate transporter expression. Glutamate transporter subtype 1 (GLT-1) is
      predominant in cortex (CTX), while it plays an inferior role in cerebellum (CER).
      Here, we set out to identify regulatory elements that could account for the
      differences in brain region-specific activity as well as response to
      dexamethasone (DEX) or epigenetic factors. We found a distal promoter element at
      the shore of the CpG island exhibiting enhancer function in response to DEX in
      reporter gene assays. This shore region showed slight enrichment in repressive
      trimethyl-histone H3 (Lys27) and under-representation of acetyl-histone H4 (H4ac)
      marks in DEX nonresponsive CER astrocytes as determined by chromatin
      immunoprecipitation. In addition, CpG sites of the shore region displayed higher
      methylation in CER than in CTX cells. Targeted in vitro methylation of CpG sites
      within the shore abrogated the stimulatory effects of DEX. Interestingly, the
      shore was characterized by a pronounced epigenetic plasticity in CTX cells since
      DEX exposure elicited an increase of H4ac in CTX in comparison to DEX
      nonresponsive CER. The transcriptional activity of this region was also affected
      by histone deacetylase inhibitors in a methylation- and brain region-dependent
      manner. Together, our study highlights the impact of an epigenetically adaptive
      DNA element of the GLT-1 promoter being decisive for brain region-specific
      activity and reactivity.

PMID- 22593011
TI  - Fifteen years of occupational and environmental health projects support in
      Brazil, Chile, and Mexico: a report from Mount Sinai School of Medicine ITREOH
      program, 1995-2010.
AB  - BACKGROUND: The Fogarty International Center of the National Institutes of Health
      created the International Training and Research Program in Occupational and
      Environmental Health (ITREOH program) in 1995 with the aim to train environmental
      and occupational health scientists in developing countries. Mount Sinai School of
      Medicine was a grantee of this program since its inception, partnering with
      research institutions in Brazil, Chile, and Mexico. This article evaluates Mount
      Sinai's program in order to determine whether it has contributed to the specific
      research capacity needs of the international partners. METHODS: Information was
      obtained from: (a) international and regional scientific literature databases;
      (b) databases from the three participating countries; and (c) MSSM ITREOH Program
      Database. RESULTS: Most of the research projects supported by the program were
      consistent with the themes found to be top priorities for the partner countries
      based on mortality/morbidity and research themes in the literature. Indirect
      effects of the training and the subsequent research projects completed by the
      trained fellows in the program included health policy changes and development of
      collaborative international projects. CONCLUSION: International research training
      programs, such as the MSSM ITREOH, that strengthen scientific research capacity
      in occupational and environmental health in Latin America can make a significant
      impact on the most pressing health issues in the partner countries.

PMID- 22593012
TI  - Impact of anemia on in-hospital, one-month and one-year mortality in patients
      with acute coronary syndrome from the Middle East.
AB  - AIM: The aim of this study was to evaluate the impact of admission anemia on in
      hospital, one-month, and one-year mortality in patients from the Middle East with
      acute coronary syndrome (ACS). METHODS: Data were analyzed from 7922 consecutive
      patients admitted to hospitals throughout six Middle-Eastern countries with the
      final diagnosis of ACS, as part of Gulf RACE II (Registry of Acute Coronary
      Events II). Anemia at admission was defined according to the World Health
      Organization definition (<13 g/dL in men and <12 g/dL in women). Analyses were
      conducted using univariate and multivariate statistical techniques. RESULTS: The
      median age of the cohort was 56 (48-65) years, with the majority being male
      (79%). Anemia at admission was present in 2241 patients (28%). Patients with
      anemia were more likely to have in-hospital complications including heart
      failure, recurrent ischemia, re-infarction, cardiogenic shock, stroke, and major
      bleed. Even after adjustment, anemia was still associated with mortality at in
      hospital (odds ratio [OR]=1.71, 95% confidence interval [CI], 1.34-2.17;
      P<0.001), at one-month (OR=1.34, 95% CI, 1.06-1.71; P=0.016), and at one-year
      (OR=1.22, 95% CI, 1.01-1.49; P=0.049) post-admission with ACS. CONCLUSIONS:
      Admission anemia in patients with ACS from six Middle-Eastern countries was
      strongly associated with mortality at in-hospital, one-month, and at one-year.
      Hence, admission anemia must be considered in the initial risk assessment of ACS
      patients along with other risk scores.

PMID- 22593013
TI  - The dynamical response of hen egg white lysozyme to the binding of a carbohydrate
      ligand.
AB  - It has become clear that the binding of small and large ligands to proteins can
      invoke significant changes in side chain and main chain motion in the fast
      picosecond to nanosecond timescale. Recently, the use of a "dynamical proxy" has
      indicated that changes in these motions often reflect significant changes in
      conformational entropy. These entropic contributions are sometimes of the same
      order as the total entropy of binding. Thus, it is important to understand the
      connections amongst motion between the manifold of states accessible to the
      native state of proteins, the corresponding entropy, and how this impacts the
      overall energetics of protein function. The interaction of proteins with
      carbohydrate ligands is central to a range of biological functions. Here, we
      examine a classic carbohydrate interaction with an enzyme: the binding of wild
      type hen egg white lysozyme (HEWL) to the natural, competitive inhibitor
      chitotriose. Using NMR relaxation experiments, backbone amide and side chain
      methyl axial order parameters were obtained across apo and chitotriose-bound
      HEWL. Upon binding, changes in the apparent amplitude of picosecond to nanosecond
      main chain and side chain motions are seen across the protein. Indeed, binding of
      chitotriose renders a large contiguous fraction of HEWL effectively completely
      rigid. Changes in methyl flexibility are most pronounced closest to the binding
      site, but average to only a small overall change in the dynamics across the
      protein. The corresponding change in conformational entropy is unfavorable and
      estimated to be a significant fraction of the total binding entropy.

PMID- 22593014
TI  - Cell surface turnover of the glutamate transporter GLT-1 is mediated by
      ubiquitination/deubiquitination.
AB  - The main glutamate transporter in the brain, GLT-1, mediates glutamatergic
      neurotransmission in both physiological and pathological conditions. GLT-1
      activity is controlled by both constitutive and regulated trafficking, and
      although recent evidence indicates that the turnover of this protein in the
      plasma membrane is accelerated by protein kinase C via an ubiquitin-dependent
      process, the mechanisms driving the constitutive trafficking of GLT-1 remain
      unexplored. Here, we used a heterologous system and primary astrocytes to
      investigate the turnover of GLT-1 and the role of ubiquitin attachment in this
      process. We show that GLT-1 is endocytosed constitutively in a clathrin-dependent
      manner, recycling the transporter into endosomes containing EEA1 and Rab4, a
      marker of rapidly recycling endosomes, and not Rab11 or Rab7, markers of the slow
      recycling and late endosomal compartments, respectively. We also show that this
      process is dependent on ubiquitination, because the inhibitor of the ubiquitin
      activating enzyme E1, 4[4-(5-nitro-furan-2-ylmethylene)-3,5-dioxo-pyrazolidin-1
      yl]-benzoic acid ethyl ester, promotes the retention of GLT-1 at the plasma
      membrane. Moreover, site-directed mutagenesis demonstrated the involvement of
      lysines 517 and 526 of GLT-1 in the constitutive internalization of the
      transporter. The translocation of GLT-1 from the recycling endosomes to the
      plasma membrane was blocked by LDN-57444, a specific inhibitor to the
      deubiquitinating enzyme (DUB) ubiquitin C-terminal hydrolase-L1, but not by an
      inhibitor of the related DUB ubiquitin C-terminal hydrolase-L3, supporting the
      existence of specific ubiquitination/deubiquitination cycles that ensure the
      correct concentrations of GLT-1 at the cell surface.

PMID- 22593015
TI  - Concise review: Blood relatives: formation and regulation of hematopoietic stem
      cells by the basic helix-loop-helix transcription factors stem cell leukemia and
      lymphoblastic leukemia-derived sequence 1.
AB  - The basic helix-loop-helix (bHLH) proteins are a large family of transcription
      factors that regulate the formation and fate of tissue stem cells. In
      hematopoiesis, the two major bHLH factors are stem cell leukemia (SCL) and
      lymphoblastic leukemia-derived sequence 1 (LYL1), both identified more than 20
      years ago in chromosomal translocations occurring in T-cell acute lymphoblastic
      leukemia. SCL was termed the master regulator of hematopoiesis following the
      observation that SCL knockout mice die from complete lack of blood formation.
      However, once established, SCL is no longer required for maintenance of
      hematopoiesis. Pull-down experiments together with add-back experiments in SCL
      null embryonic stem cells and generation of mice carrying a germline DNA binding
      mutation of SCL demonstrates that most of SCL function is mediated through the
      formation of a large DNA binding multiprotein complex with both repressor and
      activator potential. Recent genome-wide binding studies in a hematopoietic stem
      progenitor cell line suggest that SCL and LYL1 preferentially bind target DNA
      sequences as components of a heptad of transcription factors. LYL1, a paralog of
      SCL has been the forgotten sibling until recent mouse studies demonstrated that
      LYL1 replaced the function of SCL in adult hematopoiesis. Why LYL1 can replace
      the function of SCL for the maintenance but not formation of hematopoiesis
      remains a fundamental question. This review will compare and contrast the roles
      of these two transcription factors in hematopoiesis focusing on recent functional
      and genome-wide binding studies.

PMID- 22593016
TI  - Human epithelial basal cells are cells of origin of prostate cancer, independent
      of CD133 status.
AB  - Normal prostatic epithelium is composed of basal and luminal cells. Prostate
      cancer can be initiated in both benign basal and luminal stem cells, but because
      basal cell markers are not expressed in patient tumors, the former result was
      unexpected. Since the cells of origin of prostate cancer are important
      therapeutic targets, we sought to provide further proof that basal stem cells
      have tumorigenic potential. Prostatic basal cells were enriched based on
      alpha2beta1integrin(hi) expression and further enriched for stem cells using
      CD133 in nontumorigenic BPH-1 cells. Human embryonic stem cells (hESCs) were also
      used as a source of normal stem cells. To test their tumorigenicity, we used two
      alternate stromal-based approaches; (a) recombination with human cancer
      associated fibroblasts (CAFs) or (b) recombination with embryonic stroma
      (urogenital mesenchyme) and treated host mice with testosterone and 17beta
      estradiol. Enriched alpha2beta1integrin(hi) basal cells from BPH-1 cells resulted
      in malignant tumor formation using both assays of tumorigenicity. Surprisingly,
      the tumorigenic potential did not reside in the CD133(+) stem cells but was
      consistently observed in the CD133(-) population. CAFs also failed to induce
      prostatic tumors from hESCs. These data confirmed that benign human basal cells
      include cells of origin of prostate cancer and reinforced their importance as
      therapeutic targets. In addition, our data suggested that the more proliferative
      CD133(-) basal cells are more susceptible to tumorigenesis compared to the
      CD133(+)-enriched stem cells. These findings challenge the current dogma that
      normal stem cells and cells of origin of cancer are the same cell type(s).

PMID- 22593017
TI  - Age-related changes in speed and mechanism of adult skeletal muscle stem cell
      migration.
AB  - Skeletal muscle undergoes a progressive age-related loss in mass and function.
      Preservation of muscle mass depends in part on satellite cells, the resident stem
      cells of skeletal muscle. Reduced satellite cell function may contribute to the
      age-associated decrease in muscle mass. Here, we focused on characterizing the
      effect of age on satellite cell migration. We report that aged satellite cells
      migrate at less than half the speed of young cells. In addition, aged cells show
      abnormal membrane extension and retraction characteristics required for amoeboid
      based cell migration. Aged satellite cells displayed low levels of integrin
      expression. By deploying a mathematical model approach to investigate mechanism
      of migration, we have found that young satellite cells move in a random
      "memoryless" manner, whereas old cells demonstrate superdiffusive tendencies.
      Most importantly, we show that nitric oxide, a key regulator of cell migration,
      reversed the loss in migration speed and reinstated the unbiased mechanism of
      movement in aged satellite cells. Finally, we found that although hepatocyte
      growth factor increased the rate of aged satellite cell movement, it did not
      restore the memoryless migration characteristics displayed in young cells. Our
      study shows that satellite cell migration, a key component of skeletal muscle
      regeneration, is compromised during aging. However, we propose clinically
      approved drugs could be used to overcome these detrimental changes.

PMID- 22593019
TI  - Receptor activator of NF-kappaB ligand promotes proliferation of a putative
      mammary stem cell unique to the lactating epithelium.
AB  - In mice, CD49f(hi) mammary stem cells (MaSCs) asymmetrically divide to generate
      CD49f(+) committed progenitor cells that differentiate into CD49f(-) phenotypes
      of the milk-secreting tissue at the onset of pregnancy. We show CD49f(+) primary
      mammary epithelial cells (PMECs) isolated from lactating tissue uniquely respond
      to pregnancy-associated hormones (PAH) compared with CD49f(+) cells from
      nonlactating tissue. Differentiation of CD49f(+) PMEC in extracellular matrix
      produces CD49f(-) luminal cells to form differentiated alveoli. The PAH prolactin
      and placental lactogen specifically stimulate division of CD49f(-) luminal cells,
      while receptor activator of nuclear factor (NF)-kappaB ligand (RANKL)
      specifically stimulates division of basal CD49f(+) cells. In nondifferentiating
      conditions, we observed a greater proportion of multipotent self-renewing cells,
      and RANKL treatment activated the RANK pathway in these cultures. Furthermore, we
      observed the deposition of calcium nodules in a proportion of these cells. These
      data imply that a MaSC unique to the lactating breast exists in humans, which
      generates progeny with discrete lineages and distinct response to PAH.

PMID- 22593018
TI  - Enhanced homing permeability and retention of bone marrow stromal cells by
      noninvasive pulsed focused ultrasound.
AB  - Bone marrow stromal cells (BMSCs) have shown significant promise in the treatment
      of disease, but their therapeutic efficacy is often limited by inefficient homing
      of systemically administered cells, which results in low number of cells
      accumulating at sites of pathology. BMSC home to areas of inflammation where
      local expression of integrins and chemokine gradients is present. We demonstrated
      that nondestructive pulsed focused ultrasound (pFUS) exposures that emphasize the
      mechanical effects of ultrasound-tissue interactions induced local and transient
      elevations of chemoattractants (i.e., cytokines, integrins, and growth factors)
      in the murine kidney. pFUS-induced upregulation of cytokines occurred through
      approximately 1 day post-treatment and returned to contralateral kidney levels by
      day 3. This window of significant increases in cytokine expression was
      accompanied by local increases of other trophic factors and integrins that have
      been shown to promote BMSC homing. When BMSCs were intravenously administered
      following pFUS treatment to a single kidney, enhanced homing, permeability, and
      retention of BMSC was observed in the treated kidney versus the contralateral
      kidney. Histological analysis revealed up to eight times more BMSC in the
      peritubular regions of the treated kidneys on days 1 and 3 post-treatment.
      Furthermore, cytokine levels in pFUS-treated kidneys following BMSC
      administration were found to be similar to controls, suggesting modulation of
      cytokine levels by BMSC. pFUS could potentially improve cell-based therapies as a
      noninvasive modality to target homing by establishing local chemoattractant
      gradients and increasing expression of integrins to enhance tropism of cells
      toward treated tissues.

PMID- 22593021
TI  - Transduction of neural precursor cells with TAT-heat shock protein 70 chaperone:
      therapeutic potential against ischemic stroke after intrastriatal and systemic
      transplantation.
AB  - Novel therapeutic concepts against cerebral ischemia focus on cell-based
      therapies in order to overcome some of the side effects of thrombolytic therapy.
      However, cell-based therapies are hampered because of restricted understanding
      regarding optimal cell transplantation routes and due to low survival rates of
      grafted cells. We therefore transplanted adult green fluorescence protein
      positive neural precursor cells (NPCs) either intravenously (systemic) or
      intrastriatally (intracerebrally) 6 hours after stroke in mice. To enhance
      survival of NPCs, cells were in vitro protein-transduced with TAT-heat shock
      protein 70 (Hsp70) before transplantation followed by a systematic analysis of
      brain injury and underlying mechanisms depending on cell delivery routes.
      Transduction of NPCs with TAT-Hsp70 resulted in increased intracerebral numbers
      of grafted NPCs after intracerebral but not after systemic transplantation.
      Whereas systemic delivery of either native or transduced NPCs yielded sustained
      neuroprotection and induced neurological recovery, only TAT-Hsp70-transduced NPCs
      prevented secondary neuronal degeneration after intracerebral delivery that was
      associated with enhanced functional outcome. Furthermore, intracerebral
      transplantation of TAT-Hsp70-transduced NPCs enhanced postischemic neurogenesis
      and induced sustained high levels of brain-derived neurotrophic factor, glial
      cell line-derived neurotrophic factor, and vascular endothelial growth factor in
      vivo. Neuroprotection after intracerebral cell delivery correlated with the
      amount of surviving NPCs. On the contrary, systemic delivery of NPCs mediated
      acute neuroprotection via stabilization of the blood-brain-barrier, concomitant
      with reduced activation of matrix metalloprotease 9 and decreased formation of
      reactive oxygen species. Our findings imply two different mechanisms of action of
      intracerebrally and systemically transplanted NPCs, indicating that systemic NPC
      delivery might be more feasible for translational stroke concepts, lacking a need
      of in vitro manipulation of NPCs to induce long-term neuroprotection.

PMID- 22593020
TI  - IGF-II promotes stemness of neural restricted precursors.
AB  - Insulin-like growth factor (IGF)-I and IGF-II regulate brain development and
      growth through the IGF type 1 receptor (IGF-1R). Less appreciated is that IGF-II,
      but not IGF-I, activates a splice variant of the insulin receptor (IR) known as
      IR-A. We hypothesized that IGF-II exerts distinct effects from IGF-I on neural
      stem/progenitor cells (NSPs) via its interaction with IR-A. Immunofluorescence
      revealed high IGF-II in the medial region of the subventricular zone (SVZ)
      comprising the neural stem cell niche, with IGF-II mRNA predominant in the
      adjacent choroid plexus. The IGF-1R and the IR isoforms were differentially
      expressed with IR-A predominant in the medial SVZ, whereas the IGF-1R was more
      abundant laterally. Similarly, IR-A was more highly expressed by NSPs, whereas
      the IGF-1R was more highly expressed by lineage restricted cells. In vitro, IGF
      II was more potent in promoting NSP expansion than either IGF-I or standard
      growth medium. Limiting dilution and differentiation assays revealed that IGF-II
      was superior to IGF-I in promoting stemness. In vivo, NSPs propagated in IGF-II
      migrated to and took up residence in periventricular niches while IGF-I-treated
      NSPs predominantly colonized white matter. Knockdown of IR or IGF-1R using shRNAs
      supported the conclusion that the IGF-1R promotes progenitor proliferation,
      whereas the IR is important for self-renewal. Q-PCR revealed that IGF-II
      increased Oct4, Sox1, and FABP7 mRNA levels in NSPs. Our data support the
      conclusion that IGF-II promotes the self-renewal of neural stem/progenitors via
      the IR. By contrast, IGF-1R functions as a mitogenic receptor to increase
      precursor abundance.

PMID- 22593022
TI  - Anthropology in the cognitive sciences: the value of diversity.
AB  - Beller, Bender, and Medin (this issue) offer a provocative proposal outlining
      several reasons why anthropology and the rest of cognitive science might consider
      parting ways. Among those reasons, they suggest that separation might maintain
      the diversity needed to address larger problems facing humanity, and that the
      research strategies used across the disciplines are already so diverse as to be
      incommensurate. The present paper challenges the view that research strategies
      are incommensurate and offers a multimethod approach to cultural research that
      can help to establish common ground while maintaining diversity.

PMID- 22593023
TI  - Observed connection and individuation: relation to symptoms in families of
      adolescents with bulimia nervosa.
AB  - OBJECTIVE: To examine the relation between observed familial connection and
      individuation and adolescent bulimia nervosa (BN) symptoms. METHOD: As part of a
      treatment study for adolescent BN, adolescents (n = 54) and their parents
      participated in a videotaped semi-structured interview. Participants were rated
      on observed connection and individuation from these interviews using the Scale of
      Intergenerational Relationship Quality and two measures of connection. RESULTS:
      There was a significant negative relation between individuation from parents and
      adolescent BN symptoms. Connection both to and from mothers and adolescents was
      negatively associated with BN symptoms. Increased eating concern was
      significantly associated with a greater likelihood of expressing a desire for
      more connection with the family. DISCUSSION: Investigating and understanding
      family factors present at the time of adolescent BN may assist in providing
      treatment specific to the needs of the family to best aid the adolescent's
      recovery process.

PMID- 22593026
TI  - Pseudomonas infection in children with early-onset Crohn's disease: an
      association with a mutation close to PSMG1.

PMID- 22593025
TI  - DIAPH3 governs the cellular transition to the amoeboid tumour phenotype.
AB  - Therapies for most malignancies are generally ineffective once metastasis occurs.
      While tumour cells migrate through tissues using diverse strategies, the
      signalling networks controlling such behaviours in human tumours are poorly
      understood. Here we define a role for the Diaphanous-related formin-3 (DIAPH3) as
      a non-canonical regulator of metastasis that restrains conversion to amoeboid
      cell behaviour in multiple cancer types. The DIAPH3 locus is close to RB1, within
      a narrow consensus region of deletion on chromosome 13q in prostate, breast and
      hepatocellular carcinomas. DIAPH3 silencing in human carcinoma cells destabilized
      microtubules and induced defective endocytic trafficking, endosomal accumulation
      of EGFR, and hyperactivation of EGFR/MEK/ERK signalling. Silencing also evoked
      amoeboid properties, increased invasion and promoted metastasis in mice. In human
      tumours, DIAPH3 down-regulation was associated with aggressive or metastatic
      disease. DIAPH3-silenced cells were sensitive to MEK inhibition, but showed
      reduced sensitivity to EGFR inhibition. These findings have implications for
      understanding mechanisms of metastasis, and suggest that identifying patients
      with chromosomal deletions at DIAPH3 may have prognostic value.

PMID- 22593027
TI  - Measuring molecular biomarkers in epidemiologic studies: laboratory techniques
      and biospecimen considerations.
AB  - The future of personalized medicine depends on the ability to efficiently and
      rapidly elucidate a reliable set of disease-specific molecular biomarkers. High
      throughput molecular biomarker analysis methods have been developed to identify
      disease risk, diagnostic, prognostic, and therapeutic targets in human clinical
      samples. Currently, high throughput screening allows us to analyze thousands of
      markers from one sample or one marker from thousands of samples and will
      eventually allow us to analyze thousands of markers from thousands of samples.
      Unfortunately, the inherent nature of current high throughput methodologies,
      clinical specimens, and cost of analysis is often prohibitive for extensive high
      throughput biomarker analysis. This review summarizes the current state of high
      throughput biomarker screening of clinical specimens applicable to genetic
      epidemiology and longitudinal population-based studies with a focus on
      considerations related to biospecimens, laboratory techniques, and sample
      pooling.

PMID- 22593024
TI  - Sensing the messenger: the diverse ways that bacteria signal through c-di-GMP.
AB  - An intracellular second messenger unique to bacteria, c-di-GMP, has gained
      appreciation as a key player in adaptation and virulence strategies, such as
      biofilm formation, persistence, and cytotoxicity. Diguanylate cyclases containing
      GGDEF domains and phosphodiesterases containing either EAL or HD-GYP domains have
      been identified as the enzymes controlling intracellular c-di-GMP levels, yet
      little is known regarding signal transmission and the sensory targets for this
      signaling molecule. Although limited in number, identified c-di-GMP receptors in
      bacteria are characterized by prominent diversity and multilevel impact. In
      addition, c-di-GMP has been shown to have immunomodulatory effects in mammals and
      several eukaryotic c-di-GMP sensors have been proposed. The structural biology of
      c-di-GMP receptors is a rapidly developing field of research, which holds promise
      for the development of novel therapeutics against bacterial infections. In this
      review, we highlight recent advances in identifying bacterial and eukaryotic c-di
      GMP signaling mechanisms and emphasize the need for mechanistic structure
      function studies on confirmed signaling targets.

PMID- 22593028
TI  - Determination of enantiomeric impurity in besifloxacin hydrochloride by chiral
      high-performance liquid chromatography with precolumn derivatization.
AB  - Besifloxacin hydrochloride is a novel chiral broad-spectrum fluoroquinolone
      developed for the treatment of bacterial conjunctivitis. R-besifloxacin
      hydrochloride is used in clinics as a consequence of its higher antibacterial
      activity. To establish an enantiomeric impurity determination method, some chiral
      stationary phases (CSPs) were screened. Besifloxacin enantiomers can be separated
      to a certain extent on Chiral CD-Ph (Shiseido Co., Ltd., Japan), Chiral AGP, and
      Crownpak CR (+) (Daicel Chemical IND., Ltd., Japan). However, the selectivity and
      sensitivity were both unsatisfactory on these three CSPs. Therefore, Chiral AGP,
      Chiral CD-Ph, and Crownpak CR (+) were not used in the enantiomeric impurity
      determination of besifloxacin hydrochloride. The separation of enantiomers of
      besifloxacin was further performed using a precolumn derivatization chiral high
      performance liquid chromatography method. 2,3,4,6-Tetra-O-acetyl-beta-D
      glucopyranosyl isothiocyanate was used as the derivatization reagent.
      Besifloxacin enantiomer derivates were well separated on a C(18) column (250 *
      4.6 mm, 5 um) with a mobile phase that consisted of methanol-KH(2)PO(4) buffer
      solution (20 mM; pH 3.0) (50:50, v/v). Selectivity, sensitivity, linearity,
      accuracy, precision, stability, and robustness of this method were all satisfied
      with the method validation requirement. The method was suitable for the quality
      control of enantiomeric impurity in besifloxacin hydrochloride.

PMID- 22593030
TI  - Artificial egg stalks made of a recombinantly produced lacewing silk protein.
AB  - Rigid threads: Lacewings protect their eggs from predators by laying them on
      small stalks (see picture). The stalks have good mechanical properties and,
      unlike most other silks, a cross beta structure. An artificial egg stalk was
      produced using a designed recombinant variant of a sequenced lacewing egg stalk
      protein, and it attained 90 % of the tensile strength of a natural egg stalk.

PMID- 22593029
TI  - Sequence-dependent backbone dynamics of a viral fusogen transmembrane helix.
AB  - The transmembrane domains of membrane fusogenic proteins are known to contribute
      to lipid bilayer mixing as indicated by mutational studies and functional
      reconstitution of peptide mimics. Here, we demonstrate that mutations of a GxxxG
      motif or of Ile residues, that were previously shown to compromise the
      fusogenicity of the Vesicular Stomatitis virus G-protein transmembrane helix,
      reduce its backbone dynamics as determined by deuterium/hydrogen-exchange
      kinetics. Thus, the backbone dynamics of these helices may be linked to their
      fusogenicity which is consistent with the known over-representation of Gly and
      Ile in viral fusogen transmembrane helices. The transmembrane domains of membrane
      fusogenic proteins are known to contribute to lipid bilayer mixing. Our present
      results demonstrate that mutations of certain residues, that were previously
      shown to compromise the fusogenicity of the Vesicular Stomatitis virus G-protein
      transmembrane helix, reduce its backbone dynamics. Thus, the data suggest a
      relationship between sequence, backbone dynamics, and fusogenicity of
      transmembrane segments of viral fusogenic proteins.

PMID- 22593031
TI  - Predicting drug metabolism by cytochrome P450 2C9: comparison with the 2D6 and
      3A4 isoforms.
AB  - By the use of knowledge gained through modeling of drug metabolism mediated by
      the cytochrome P450 2D6 and 3A4 isoforms, we constructed a 2D-based model for
      site-of-metabolism prediction for the cytochrome P450 2C9 isoform. The
      similarities and differences between the models for the 2C9 and 2D6 isoforms are
      discussed through structural knowledge from the X-ray crystal structures and
      trends in experimental data. The final model was validated on an independent test
      set, resulting in an area under the curve value of 0.92, and a site of metabolism
      was found among the top two ranked atoms for 77% of the compounds.

PMID- 22593032
TI  - Density estimation of a biomedical variable subject to measurement error using an
      auxiliary set of replicate observations.
AB  - Correcting for measurement error when estimating the density of a routinely
      collected biomedical variable is an important issue when describing reference
      values for both healthy and pathological states. The present work addresses the
      problem of estimating the density of a biomedical variable observed with
      measurement error without any a priori knowledge on the error density. Assuming
      the availability of a sample of replicate observations, either internal or
      external, which is generally easily obtained in clinical settings, we propose an
      estimator based on the non-parametric deconvolution theory with an adaptive
      procedure for cutoff selection, the replicates being used for an estimation of
      the error density. We illustrate this approach in two applicative examples: (i)
      the systolic blood pressure distribution density, using the Framingham Study data
      set, and (ii) the distribution of the timing of onset of pregnancy within the
      female cycle, using ultrasound measurements in the first trimester of pregnancy.

PMID- 22593033
TI  - Accounting for biases when linking empirical studies and simulation models.

PMID- 22593034
TI  - Chaetoglobosin Vb from endophytic Chaetomium globosum: absolute configuration of
      chaetoglobosins.
AB  - One new cytochalasan alkaloid, chaetoglobosin V(b) (1), together with two
      structurally related known compounds, chaetoglobosin V (2) and chaetoglobosin G
      (3), was isolated from the ethyl acetate extract of a culture of the endophytic
      fungus Chaetomium globosum, associated with the leaves of Ginkgo biloba tree. The
      structures of the isolated compounds were elucidated by spectroscopic methods
      including 1D and 2D NMR and mass spectrometry. The absolute configuration of
      chaetoglobosin V(b) (1) was established by means of electronic circular dichroism
      (CD) spectroscopy, on the basis of the comparison between the CD spectrum of (+)
      1 with that calculated with time-dependent density functional theory method for a
      simplified model. The correlation between compounds 1-3 was demonstrated by a
      biomimetic transformation of chaetoglobosin G (3) under mild conditions in
      chaetoglobosins V and V(b) (1 and 2). The isolated metabolites were tested
      against some phytopathogens.

PMID- 22593035
TI  - Age-dependent deamidation of glutamine residues in human gammaS crystallin:
      deamidation and unstructured regions.
AB  - Human aging is associated with the deterioration of long-lived proteins. Gradual
      cumulative modifications to the life-long proteins of the lens may ultimately be
      responsible for the pronounced alterations to the optical and physical properties
      that characterize lenses from older people. gammaS crystallin, a major human lens
      protein, is known to undergo several age-dependent changes. Using proteomic
      techniques, a site of deamidation involving glutamine 92 has been characterized
      and its time course established. The proportion of deamidation increased from
      birth to teen-age years and then plateaud. Deamidation at this site increased
      again in the eighth decade of life. There was no significant difference in the
      extent of deamidation between cataract and age-matched normal lenses. Gln92 is
      located in the linker region between the two domains, and the introduction of a
      negative charge at this site may alter the interaction between the two regions of
      the protein. Gln170, which is located in another unstructured part of gammaS
      crystallin, showed a similar deamidation profile to that of Gln92. As the other
      Gln residues in beta-sheet regions of gammaS crystallin appear to remain as
      amides, modification of Gln92 and Gln170 thus conforms to a pattern whereby
      deamidation is localized to the unstructured regions of long-lived proteins.

PMID- 22593036
TI  - A mild benzannulation through directed cycloaddition reactions.
AB  - Simple as ABC: Alkynyl borane cycloadditions can be substrate-directed to
      assemble aromatic difluoroboranes within an extremely mild and efficient reaction
      manifold compared to that of traditional methods (see scheme). The aromatic
      boranes are readily transformed into a range of useful products.

PMID- 22593038
TI  - Utility of drug depletion-time profiles in isolated hepatocytes for accessing
      hepatic uptake clearance: identifying rate-limiting steps and role of passive
      processes.
AB  - Drug depletion-time profiles in isolated hepatocytes, as well as microsomes, have
      become a standard method of assessing hepatic metabolic clearance in vitro. There
      is a previously described adaptation of the depletion approach to allow
      determination of hepatic uptake by transporters in addition to metabolism (Drug
      Metab Dispos 35:859-865, 2007). Dual incubations are performed where one set of
      incubations undergo conventional methodology, whereas for the second set, cells
      and media are separated for determination of drug loss from the media. The
      utility of this dual incubation approach has been assessed using eight drugs
      (atorvastatin, clarithromycin, erythromycin, fexofenadine, pitavastatin,
      repaglinide, rosuvastatin, and saquinavir) with a range of active uptake, passive
      permeability, cell binding, and metabolic characteristics. Four of these
      compounds (fexofenadine, rosuvastatin, pitavastatin, and atorvastatin) show a
      biphasic time profile when assessing drug loss from media indicative of hepatic
      uptake before elimination within the hepatocyte, which is distinct from the time
      profile in a conventional incubation, and show higher clearances. The four other
      compounds (clarithromycin, saquinavir, erythromycin, and repaglinide) show
      identical depletion-time profiles (and clearances) in both sets of incubations.
      Whether or not the biphasic nature (and higher clearance) is evident, indicating
      transporter activity for a particular drug, appears to be dependent on its
      passive permeability. Using the parameter K(pu) to reflect the relative
      importance of hepatic transporters versus passive diffusion, a value of 10 was
      identified as a cutoff for whether the biphasic nature was evident; those
      compounds in excess of 10 show this characteristic clearly. There appears to be
      no relationship between the presence of the biphasic nature and any other
      parameter, including cellular binding, extent of metabolism, or the magnitude of
      active uptake.

PMID- 22593039
TI  - Ionic surfactants induce amphiphilic tris(urea) hydrogel formation.

PMID- 22593037
TI  - Potent inhibition of human sulfotransferase 1A1 by 17alpha-ethinylestradiol: role
      of 3'-phosphoadenosine 5'-phosphosulfate binding and structural rearrangements in
      regulating inhibition and activity.
AB  - Sulfotransferase (SULT) 1A1 is the major drug/xenobiotic-conjugating SULT isoform
      in human liver because of its broad substrate reactivity and high expression
      level. SULT1A1 sulfates estrogens with low micromolar K(m) values consistent with
      its affinity for sulfation of many small phenolic compounds. Binding studies
      showed the unexpected ability of 17alpha-ethinylestradiol (EE2) to bind and
      inhibit SULT1A1 activity toward p-nitrophenol and beta-naphthol at low nanomolar
      concentrations, whereas EE2 was not sulfated until significantly higher
      concentrations were reached. EE2 had a K(i) of 10 nM for inhibiting p-nitrophenol
      and beta-naphthol sulfation and inhibited 17beta-estradiol (E2) sulfation in
      intact human MCF-7 breast cancer cells with a K(i) of 19 nM. In contrast, the
      K(m) for EE2 sulfation by SULT1A1 was 700 nM. The K(d) for EE2 binding of pure
      SULT1A1 was 0.5 +/- 0.15 MUM; however, the K(d) for EE2 binding to the SULT1A1
      PAP complex was >100-fold lower (4.3 +/- 1.7 nM). The K(d) for E2 binding to
      SULT1A1 changed from 2.3 +/- 0.9 to 1.2 +/- 0.56 MUM in the presence of PAP.
      Docking studies with E2 indicate that E2 binds in a competent orientation in the
      resolved structure of SULT1A1 in the both presence and absence of 3'
      phosphoadenosine 5'-phosphosulfate (PAPS). However, EE2 binds in a catalytically
      competent orientation in the absence of PAPS but in a noncompetent orientation
      via formation of a charge interaction with Tyr108 if PAPS is bound first. In
      conclusion, EE2 is a potent inhibitor, but not a substrate, of SULT1A1 at low
      nanomolar concentrations, indicating the possibility of drug-drug interactions
      during contraceptive therapy.

PMID- 22593040
TI  - A functional polymorphism C-1310G in the promoter region of Ku70/XRCC6 is
      associated with risk of renal cell carcinoma.
AB  - The DNA repair gene Ku70 plays a key role in the DNA double strand break (DSB)
      repair system. Defects in DSB repair capacity can lead to genomic instability. We
      hypothesized that the Ku70 C-1310G polymorphism (rs2267437) was associated with
      risk of renal cell carcinoma (RCC). We genotyped the Ku70 C-1310G polymorphism in
      a case-control study of 620 patients and 623 controls in a Chinese population and
      assessed the effects of C-1310G polymorphism on RCC susceptibility and survival.
      We then examined the functionality of this polymorphism. Compared with the Ku70
      1310CC genotype, the CG and CG/GG genotypes had a significantly increased risk of
      RCC [adjusted odds ratio (OR) = 1.47, 95% confidence interval (CI) = 1.16-1.87
      for CG and OR = 1.47, 95% CI = 1.16-1.86 for CG/GG]. However, the C-1310G
      polymorphism did not influence the survival of RCC. The in vivo experiments with
      normal renal tissues revealed statistically significantly lower Ku70 mRNA
      expression in samples with CG/GG genotypes relative to those with the CC genotype
      (P < 0.05). In vitro luciferase assays in various cell lines showed lower
      luciferase activity for the -1310G allele than for the -1310C allele. These
      results suggest that the Ku70 C-1310G polymorphism is involved in the etiology of
      RCC and thus may be a marker for genetic susceptibility to RCC in Chinese
      populations. Larger studies are warranted to validate our findings.

PMID- 22593042
TI  - Linking photo- and redoxactive phthalocyanines covalently to graphene.
AB  - "Green" graphene: For the first time, the covalent attachment of a light
      harvesting and electron-donating phthalocyanine to the basal plane of few-layer
      graphene is reported. Physicochemical characterizations reveal an ultrafast
      charge separation from the photoexcited phthalocyanine to few-layer graphene
      followed by a slower charge recombination.

PMID- 22593043
TI  - Drug resistance associates with activation of Nrf2 in MCF-7/DOX cells, and
      wogonin reverses it by down-regulating Nrf2-mediated cellular defense response.
AB  - Acquired resistance to doxorubicin (DOX) is a serious therapeutic problem in
      breast cancer patients. In this study, we investigated whether nuclear factor
      erythroid 2-related factor 2 (Nrf2) was associated with drug resistant in DOX
      resistant MCF-7 (MCF-7/DOX) cells, and if wogonin, a flavonoid isolated from the
      root of Scutellaria baicalensis Georgi, could reverse drug resistance in MCF
      7/DOX cells. We found that the endogenous expression of Nrf2 as well as its
      target proteins heme oxygenase-1 (HO-1), NADP(H):quinone oxidoreductase (NQO) in
      MCF-7/DOX cells was higher than that in MCF-7 cells. Tert-butylhydroquinone
      treatment increased the expression Nrf2, HO-1, and NQO-1, and enhanced resistance
      of MCF-7 cells to DOX. Similarly, intracellular Nrf2 protein level was
      significantly decreased in MCF-7/DOX cells and DOX resistance was partially
      reversed by Nrf2 siRNA. Wogonin downregulated the Nrf2-dependent response and
      partly reversed DOX resistance in MCF-7/DOX cells. These results suggested that
      activation of Nrf2 was associated with drug resistance in MCF-7/DOX cells.
      Wogonin reversed drug resistance and its reversal mechanism might be due to the
      suppression of Nrf2 signaling pathway, indicating the feasibility of using Nrf2
      inhibitors to increase efficacy of chemotherapeutic drugs.

PMID- 22593041
TI  - Designing specific protein-protein interactions using computation, experimental
      library screening, or integrated methods.
AB  - Given the importance of protein-protein interactions for nearly all biological
      processes, the design of protein affinity reagents for use in research, diagnosis
      or therapy is an important endeavor. Engineered proteins would ideally have high
      specificities for their intended targets, but achieving interaction specificity
      by design can be challenging. There are two major approaches to protein design or
      redesign. Most commonly, proteins and peptides are engineered using experimental
      library screening and/or in vitro evolution. An alternative approach involves
      using protein structure and computational modeling to rationally choose sequences
      predicted to have desirable properties. Computational design has successfully
      produced novel proteins with enhanced stability, desired interactions and
      enzymatic function. Here we review the strengths and limitations of experimental
      library screening and computational structure-based design, giving examples where
      these methods have been applied to designing protein interaction specificity. We
      highlight recent studies that demonstrate strategies for combining computational
      modeling with library screening. The computational methods provide focused
      libraries predicted to be enriched in sequences with the properties of interest.
      Such integrated approaches represent a promising way to increase the efficiency
      of protein design and to engineer complex functionality such as interaction
      specificity.

PMID- 22593044
TI  - Sex steroids and the organization of the human brain.

PMID- 22593046
TI  - Equivalent representation of real and illusory contours in macaque V4.
AB  - The cortical processing of illusory contours provides a unique window for
      exploring the brain mechanisms underlying visual perception. Previous
      electrophysiological single-cell recordings demonstrate that a subgroup of cells
      in macaque V1 and V2 signal the presence of illusory contours, whereas recent
      human brain imaging studies reveal higher-order visual cortices playing a central
      role in illusory figure processing. It seems that the processing of illusory
      contours/figures may engage multiple cortical interactions between hierarchically
      organized processing stages in the ventral visual pathway of primates. However,
      it is not yet known in which brain areas illusory contours are represented in the
      same manner as real contours at both the population and single-cell levels. Here,
      by combining intrinsic optical imaging in anesthetized rhesus macaques with
      single-cell recordings in awake ones, we found a complete overlap of orientation
      domains in visual cortical area V4 for processing real and illusory contours. In
      contrast, the orientation domains mapped in early visual areas V1 and V2 mainly
      encoded the local physical stimulus features inducing the subjective perception
      of global illusory contours. Our results indicate that real and illusory contours
      are encoded equivalently by the same functional domains in V4, suggesting that V4
      is a key cortical locus for integration of local features into global contours.

PMID- 22593045
TI  - Nonsynaptic NMDA receptors mediate activity-dependent plasticity of gap
      junctional coupling in the AII amacrine cell network.
AB  - Many neurons are coupled by electrical synapses into networks that have emergent
      properties. In the retina, coupling in these networks is dynamically regulated by
      changes in background illumination, optimizing signal integration for the visual
      environment. However, the mechanisms that control this plasticity are poorly
      understood. We have investigated these mechanisms in the rabbit AII amacrine
      cell, a multifunctional retinal neuron that forms an electrically coupled network
      via connexin 36 (Cx36) gap junctions. We find that presynaptic activity of
      glutamatergic ON bipolar cells drives increased phosphorylation of Cx36,
      indicative of increased coupling in the AII network. The phosphorylation is
      dependent on activation of nonsynaptic NMDA receptors that colocalize with Cx36
      on AII amacrine cells, and is mediated by CaMKII. This activity-dependent
      increase in Cx36 phosphorylation works in opposition to dopamine-driven reduction
      of phosphorylation, establishing a local dynamic regulatory mechanism, and
      accounting for the nonlinear control of AII coupling by background illumination.

PMID- 22593047
TI  - kappa-Opioid receptors within the nucleus accumbens shell mediate pair bond
      maintenance.
AB  - The prairie vole is a socially monogamous species in which breeder pairs
      typically show strong and selective pair bonds. The establishment of a pair bond
      is associated with a behavioral transition from general affiliation to aggressive
      rejection of novel conspecifics. This "selective aggression" is indicative of
      mate guarding that is necessary to maintain the initial pair bond. In the
      laboratory, the neurobiology of this behavior is studied using resident-intruder
      testing. Although it is well established that social behaviors in other species
      are mediated by endogenous opioid systems, opiate regulation of pair bond
      maintenance has never been studied. Here, we used resident-intruder testing to
      determine whether endogenous opioids within brain motivational circuitry mediate
      selective aggression in prairie voles. We first show that peripheral blockade of
      kappa-opioid receptors with the antagonist norbinaltorphimine (nor-BNI; 100
      mg/kg), but not with the preferential MU-opioid receptor antagonist naloxone (1,
      10, or 30 mg/kg), decreased selective aggression in males. We then provide the
      first comprehensive characterization of kappa- and MU-opioid receptors in the
      prairie vole brain. Finally, we demonstrate that blockade of kappa-opioid
      receptors (500 ng nor-BNI) within the nucleus accumbens (NAc) shell abolishes
      selective aggression in both sexes, but blockade of these receptors within the
      NAc core enhances this behavior specifically in females. Blockade of kappa-opioid
      receptors within the ventral pallidum or MU-opioid receptors with the specific MU
      opioid receptor antagonist H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-PenThr-NH2 (1 ng CTAP)
      within the NAc shell had no effect in either sex. Thus, kappa-opioid receptors
      within the NAc shell mediate aversive social motivation that is critical for pair
      bond maintenance.

PMID- 22593048
TI  - Calcium-dependent but action potential-independent BCM-like metaplasticity in the
      hippocampus.
AB  - The Bienenstock, Cooper and Munro (BCM) computational model, which incorporates a
      metaplastic sliding threshold for LTP induction, accounts well for experience
      dependent changes in synaptic plasticity in the visual cortex. BCM-like
      metaplasticity over a shorter timescale has also been observed in the
      hippocampus, thus providing a tractable experimental preparation for testing
      specific predictions of the model. Here, using extracellular and intracellular
      electrophysiological recordings from acute rat hippocampal slices, we tested the
      critical BCM predictions (1) that high levels of synaptic activation will induce
      a metaplastic state that spreads across dendritic compartments, and (2) that
      postsynaptic cell-firing is the critical trigger for inducing that state. In
      support of the first premise, high-frequency priming stimulation inhibited
      subsequent long-term potentiation and facilitated subsequent long-term depression
      at synapses quiescent during priming, including those located in a dendritic
      compartment different to that of the primed pathway. These effects were not
      dependent on changes in synaptic inhibition or NMDA/metabotropic glutamate
      receptor function. However, in contrast to the BCM prediction, somatic action
      potentials during priming were neither necessary nor sufficient to induce the
      metaplasticity effect. Instead, in broad agreement with derivatives of the BCM
      model, calcium as released from intracellular stores and triggered by M1
      muscarinic acetylcholine receptor activation was critical for altering subsequent
      synaptic plasticity. These results indicate that synaptic plasticity in stratum
      radiatum of CA1 can be homeostatically regulated by the cell-wide history of
      synaptic activity through a calcium-dependent but action potential-independent
      mechanism.

PMID- 22593049
TI  - Maladaptive dendritic spine remodeling contributes to diabetic neuropathic pain.
AB  - Diabetic neuropathic pain imposes a huge burden on individuals and society, and
      represents a major public health problem. Despite aggressive efforts, diabetic
      neuropathic pain is generally refractory to available clinical treatments. A
      structure-function link between maladaptive dendritic spine plasticity and pain
      has been demonstrated previously in CNS and PNS injury models of neuropathic
      pain. Here, we reasoned that if dendritic spine remodeling contributes to
      diabetic neuropathic pain, then (1) the presence of malformed spines should
      coincide with the development of pain, and (2) disrupting maladaptive spine
      structure should reduce chronic pain. To determine whether dendritic spine
      remodeling contributes to neuropathic pain in streptozotocin (STZ)-induced
      diabetic rats, we analyzed dendritic spine morphology and electrophysiological
      and behavioral signs of neuropathic pain. Our results show changes in dendritic
      spine shape, distribution, and shape on wide-dynamic-range (WDR) neurons within
      lamina IV-V of the dorsal horn in diabetes. These diabetes-induced changes were
      accompanied by WDR neuron hyperexcitability and decreased pain thresholds at 4
      weeks. Treatment with NSC23766 (N(6)-[2-[[4-(diethylamino)-1-methylbutyl]amino]-6
      methyl-4-pyrimidinyl]-2-methyl-4,6-quinolinediamine trihydrochloride), a Rac1
      specific inhibitor known to interfere with spine plasticity, decreased the
      presence of malformed spines in diabetes, attenuated neuronal hyperresponsiveness
      to peripheral stimuli, reduced spontaneous firing activity from WDR neurons, and
      improved nociceptive mechanical pain thresholds. At 1 week after STZ injection,
      animals with hyperglycemia with no evidence of pain had few or no changes in
      spine morphology. These results demonstrate that diabetes-induced maladaptive
      dendritic spine remodeling has a mechanistic role in neuropathic pain. Molecular
      pathways that control spine morphogenesis and plasticity may be promising future
      targets for treatment.

PMID- 22593051
TI  - Genetic analysis of ecdysis behavior in Drosophila reveals partially overlapping
      functions of two unrelated neuropeptides.
AB  - Ecdysis behavior allows insects to shed their old exoskeleton at the end of every
      molt. It is controlled by a suite of interacting hormones and neuropeptides, and
      has served as a useful behavior for understanding how bioactive peptides regulate
      CNS function. Previous findings suggest that crustacean cardioactive peptide
      (CCAP) activates the ecdysis motor program; the hormone bursicon is believed to
      then act downstream of CCAP to inflate, pigment, and harden the exoskeleton of
      the next stage. However, the exact roles of these signaling molecules in
      regulating ecdysis remain unclear. Here we use a genetic approach to investigate
      the functions of CCAP and bursicon in Drosophila ecdysis. We show that null
      mutants in CCAP express no apparent defects in ecdysis and postecdysis, producing
      normal adults. By contrast, a substantial fraction of flies genetically null for
      one of the two subunits of bursicon [encoded by the partner of bursicon gene
      (pburs)] show severe defects in ecdysis, with escaper adults exhibiting the
      expected failures in wing expansion and exoskeleton pigmentation and hardening.
      Furthermore, flies lacking both CCAP and bursicon show much more severe defects
      at ecdysis than do animals null for either neuropeptide alone. Our results show
      that the functions thought to be subserved by CCAP are partially effected by
      bursicon, and that bursicon plays an important and heretofore undescribed role in
      ecdysis behavior itself. These findings have important implications for
      understanding the regulation of this vital insect behavior and the mechanisms by
      which hormones and neuropeptides control the physiology and behavior of animals.

PMID- 22593050
TI  - Egr-1 induces DARPP-32 expression in striatal medium spiny neurons via a
      conserved intragenic element.
AB  - DARPP-32 (dopamine and adenosine 3', 5'-cyclic monophosphate cAMP-regulated
      phosphoprotein, 32 kDa) is a striatal-enriched protein that mediates signaling by
      dopamine and other first messengers in the medium spiny neurons. The
      transcriptional mechanisms that regulate striatal DARPP-32 expression remain
      enigmatic and are a subject of much interest in the efforts to induce a striatal
      phenotype in stem cells. We report the identification and characterization of a
      conserved region, also known as H10, in intron IV of the gene that codes for
      DARPP-32 (Ppp1r1b). This DNA sequence forms multiunit complexes with nuclear
      proteins from adult and embryonic striata of mice and rats. Purification of
      proteins from these complexes identified early growth response-1 (Egr-1). The
      interaction between Egr-1 and H10 was confirmed in vitro and in vivo by super
      shift and chromatin immunoprecipitation assays, respectively. Importantly, brain
      derived neurotrophic factor (BDNF), a known inducer of DARPP-32 and Egr-1
      expression, enhanced Egr-1 binding to H10 in vitro. Moreover, overexpression of
      Egr-1 in primary striatal neurons induced the expression of DARPP-32, whereas a
      dominant-negative Egr-1 blocked DARPP-32 induction by BDNF. Together, this study
      identifies Egr-1 as a transcriptional activator of the Ppp1r1b gene and provides
      insight into the molecular mechanisms that regulate medium spiny neuron
      maturation.

PMID- 22593052
TI  - Dopaminergic modulation of mitral cells and odor responses in the zebrafish
      olfactory bulb.
AB  - In the olfactory bulb, the modulatory neurotransmitter dopamine (DA) is
      coexpressed with GABA by local interneurons, but its role in odor processing
      remains obscure. We examined functions of DA mediated by D2-like receptors in the
      olfactory bulb of adult zebrafish by pharmacology, whole-cell recordings, calcium
      imaging, and optogenetics. Bath application of DA had no detectable effect on
      odorant-evoked sensory input. DA directly hyperpolarized mitral cells (MCs) via
      D2-like receptors and slightly increased their response gain. Consistent with
      this effect on input-output functions of MCs, small odorant responses were
      suppressed, whereas strong responses were enhanced in the presence of DA. These
      effects increased the root-mean-square contrast of population activity patterns
      but did not reduce their correlations. Optical stimulation of interneurons
      expressing channelrhodopsin-2 evoked fast GABAergic inhibitory currents in mitral
      cells but failed to activate D2 receptor-mediated currents when stimuli were
      short. Prolonged stimulus trains, however, activated a slow hyperpolarizing
      current that was blocked by an antagonist of D2-like receptors. GABA and DA are
      therefore both released from interneurons by electrical activity and
      hyperpolarize MCs, but D2-dependent dopaminergic effects occur on slower
      timescales. Additional effects of DA may be mediated by D1-like receptors. These
      results indicate that DA acts on D2-like receptors via asynchronous release
      and/or volume transmission and implicate DA in the slow adaptation of circuit
      function. The shift of the membrane potential away from spike threshold could
      adapt mitral cells to background input without compromising their sensitivity.

PMID- 22593053
TI  - Developmental changes in medial auditory thalamic contributions to associative
      motor learning.
AB  - Eyeblink conditioning (EBC) was used in the current study to examine the
      mechanisms underlying the ontogeny of associative motor learning in rats.
      Eyeblink conditioning emerges ontogenetically between postnatal day 17 (P17) and
      P24 in rats. Previous studies used electrical stimulation to show that the
      ontogeny of EBC is influenced by developmental changes in input from the medial
      auditory thalamus to the pontine nuclei, which in turn affects input to the
      cerebellum. The current study used tetrode recordings to examine the ontogeny of
      medial auditory thalamic sensory responses to the conditioned stimulus (CS) and
      learning-related activity during EBC. Rat pups were implanted with multiple
      tetrodes in the medial nucleus of the medial geniculate (MGm) and suprageniculate
      (SG) and trained on delay EBC on P17-P19, P24-P26, or P31-P33 while recording
      spike activity. Developmental changes in MGm and SG sensory-related activity were
      found during a pretraining session with unpaired presentations of the auditory CS
      and periorbital stimulation unconditioned stimulus (US). Substantial
      developmental changes were observed in learning-related activity in the MGm and
      SG during CS-US paired training. The ontogenetic changes in learning-related
      activity may be related to developmental changes in input to the medial auditory
      thalamus from the amygdala and cerebellum. The findings suggest that the ontogeny
      of associative motor learning involves developmental changes in sensory input to
      the thalamus, amygdala input to the thalamus, thalamic input to the pontine
      nuclei, and cerebellar feedback to the thalamus.

PMID- 22593054
TI  - Segregated pathways carrying frontally derived top-down signals to visual areas
      MT and V4 in macaques.
AB  - The bottom-up processing of visual information is strongly influenced by top-down
      signals, at least part of which is thought to be conveyed from the frontal cortex
      through the frontal eye field (FEF) and the lateral intraparietal area (LIP).
      Here we investigated the architecture of multisynaptic pathways from the frontal
      cortex to the middle temporal area (MT) of the dorsal visual stream and visual
      area 4 (V4) of the ventral visual stream in macaques. In the first series of
      experiments, the retrograde trans-synaptic tracer, rabies virus, was injected
      into MT or V4. Three days after rabies injections, the second-order
      (disynaptically connected) neuron labeling appeared in the ventral part of area
      46 (area 46v), along with the first-order (monosynaptically connected) neuron
      labeling in FEF and LIP. In the MT-injection case, second-order neurons were also
      observed in the supplementary eye field (SEF). In the next series of experiments,
      double injections of two fluorescent dyes, fast blue and diamidino yellow, were
      made into MT and V4 to examine whether the frontal inputs are mediated by
      distinct or common neuronal populations. Virtually no double-labeled neurons were
      observed in FEF or LIP, indicating that separate neuronal populations mediate the
      frontal inputs to MT and V4. The present results define that the multisynaptic
      frontal input to V4 arises primarily from area 46v, whereas the input to MT
      arises from not only area 46v but also SEF, through distinct FEF and LIP neurons.
      Segregated pathways from the frontal cortex possibly carry the functionally
      diverse top-down signals to each visual stream.

PMID- 22593055
TI  - Guidance-cue control of horizontal cell morphology, lamination, and synapse
      formation in the mammalian outer retina.
AB  - In the vertebrate retina, neuronal circuitry required for visual perception is
      organized within specific laminae. Photoreceptors convey external visual
      information to bipolar and horizontal cells at triad ribbon synapses established
      within the outer plexiform layer (OPL), initiating retinal visual processing.
      However, the molecular mechanisms that organize these three classes of neuronal
      processes within the OPL, thereby ensuring appropriate ribbon synapse formation,
      remain largely unknown. Here we show that mice with null mutations in Sema6A or
      PlexinA4 (PlexA4) exhibit a pronounced defect in OPL stratification of horizontal
      cell axons without any apparent deficits in bipolar cell dendrite or
      photoreceptor axon targeting. Furthermore, these mutant horizontal cells exhibit
      aberrant dendritic arborization and reduced dendritic self-avoidance within the
      OPL. Ultrastructural analysis shows that the horizontal cell contribution to rod
      ribbon synapse formation in PlexA4-/- retinas is disrupted. These findings define
      molecular components required for outer retina lamination and ribbon synapse
      formation.

PMID- 22593056
TI  - Intersection of reward and memory in monkey rhinal cortex.
AB  - In humans and other animals, the vigor with which a reward is pursued depends on
      its desirability, that is, on the reward's predicted value. Predicted value is
      generally context-dependent, varying according to the value of rewards obtained
      in the recent and distant past. Signals related to reward prediction and
      valuation are believed to be encoded in a circuit centered around midbrain
      dopamine neurons and their targets in the prefrontal cortex and basal ganglia.
      Notably absent from this hypothesized reward pathway are dopaminergic targets in
      the medial temporal lobe. Here we show that a key part of the medial temporal
      lobe memory system previously reported to be important for sensory mnemonic and
      perceptual processing, the rhinal cortex (Rh), is required for using memories of
      previous reward values to predict the value of forthcoming rewards. We tested
      monkeys with bilateral Rh lesions on a task in which reward size varied across
      blocks of uncued trials. In this experiment, the only cues for predicting current
      reward value are the sizes of rewards delivered in previous blocks. Unexpectedly,
      monkeys with Rh ablations, but not intact controls, were insensitive to
      differences in predicted reward, responding as if they expected all rewards to be
      of equal magnitude. Thus, it appears that Rh is critical for using memory of
      previous rewards to predict the value of forthcoming rewards. These results are
      in agreement with accumulating evidence that Rh is critical for establishing the
      relationships between temporally interleaved events, which is a key element of
      episodic memory.

PMID- 22593059
TI  - Susceptibility to PTSD-like behavior is mediated by corticotropin-releasing
      factor receptor type 2 levels in the bed nucleus of the stria terminalis.
AB  - Posttraumatic stress disorder (PTSD) is a debilitating disease, which affects 8
      10% of the population exposed to traumatic events. The factors that make certain
      individuals susceptible to PTSD and others resilient are currently unknown.
      Corticotropin-releasing factor receptor type 2 (CRFR2) has been implicated in
      mediating stress coping mechanisms. Here, we use a physiological PTSD-like animal
      model and an in-depth battery of tests that reflect the symptomology of PTSD to
      separate mice into subpopulations of "PTSD-like" and "Resilient" phenotypes. PTSD
      like mice are hypervigilant, hyperalert, insomniac, have impaired attention and
      risk assessment, as well as accompanying attenuated corticosterone levels.
      Intriguingly, PTSD-like mice show long-term robust upregulation of BNST-CRFR2
      mRNA levels, and BNST-CRFR2-specific lentiviral knockdown reduces susceptibility
      to PTSD-like behavior. Additionally, using a BNST mRNA expression array, PTSD
      like mice exhibit a general transcriptional attenuation profile, which was
      associated with upregulation of the BNST-deacetylation enzyme, HDAC5. We suggest
      PTSD to be a disease of maladaptive coping.

PMID- 22593057
TI  - NMDA receptors with incomplete Mg2+ block enable low-frequency transmission
      through the cerebellar cortex.
AB  - The cerebellar cortex coordinates movements and maintains balance by modifying
      motor commands as a function of sensory-motor context, which is encoded by mossy
      fiber (MF) activity. MFs exhibit a wide range of activity, from brief precisely
      timed high-frequency bursts, which encode discrete variables such as whisker
      stimulation, to low-frequency sustained rate-coded modulation, which encodes
      continuous variables such as head velocity. While high-frequency MF inputs have
      been shown to activate granule cells (GCs) effectively, much less is known about
      sustained low-frequency signaling through the GC layer, which is impeded by a
      hyperpolarized resting potential and strong GABA(A)-mediated tonic inhibition of
      GCs. Here we have exploited the intrinsic MF network of unipolar brush cells to
      activate GCs with sustained low-frequency asynchronous MF inputs in rat
      cerebellar slices. We find that low-frequency MF input modulates the intrinsic
      firing of Purkinje cells, and that this signal transmission through the GC layer
      requires synaptic activation of Mg2+-block-resistant NMDA receptors (NMDARs) that
      are likely to contain the GluN2C subunit. Slow NMDAR conductances sum temporally
      to contribute approximately half the MF-GC synaptic charge at hyperpolarized
      potentials. Simulations of synaptic integration in GCs show that the NMDAR and
      slow spillover-activated AMPA receptor (AMPAR) components depolarize GCs to a
      similar extent. Moreover, their combined depolarizing effect enables the fast
      quantal AMPAR component to trigger action potentials at low MF input frequencies.
      Our results suggest that the weak Mg2+ block of GluN2C-containing NMDARs enables
      transmission of low-frequency MF signals through the input layer of the
      cerebellar cortex.

PMID- 22593058
TI  - PMCA2 via PSD-95 controls calcium signaling by alpha7-containing nicotinic
      acetylcholine receptors on aspiny interneurons.
AB  - Local control of calcium concentration within neurons is critical for signaling
      and regulation of synaptic communication in neural circuits. How local control
      can be achieved in the absence of physical compartmentalization is poorly
      understood. Challenging examples are provided by nicotinic acetylcholine
      receptors that contain alpha7 nicotinic receptor subunits (alpha7-nAChRs). These
      receptors are highly permeable to calcium and are concentrated on aspiny
      dendrites of interneurons, which lack obvious physical compartments for
      constraining calcium diffusion. Using functional proteomics on rat brain, we show
      that alpha7-nAChRs are associated with plasma membrane calcium-ATPase pump
      isoform 2 (PMCA2). Analysis of alpha7-nAChR function in hippocampal interneurons
      in culture shows that PMCA2 activity limits the duration of calcium elevations
      produced by the receptors. Unexpectedly, PMCA2 inhibition triggers rapid calcium
      dependent loss of alpha7-nAChR clusters. This extreme regulatory response is
      mediated by CaMKII, involves proteasome activity, depends on the second
      intracellular loop of alpha7-nAChR subunits, and is specific in that it does not
      alter two other classes of calcium-permeable ionotropic receptors on the same
      neurons. A critical link is provided by the scaffold protein PSD-95 (postsynaptic
      density-95), which is associated with alpha7-nAChRs and constrains their mobility
      as revealed by single-particle tracking on neurons. The PSD-95 link is required
      for PMCA2-mediated removal of alpha7-nAChR clusters. This three-component
      combination of PMCA2, PSD-95, and alpha7-nAChR offers a novel mechanism for tight
      control of calcium dynamics in neurons.

PMID- 22593060
TI  - Rewiring of afferent fibers in the somatosensory thalamus of mice caused by
      peripheral sensory nerve transection.
AB  - The remodeling of neural circuitry and changes in synaptic efficacy after
      peripheral sensory nerve injury are considered the basis for functional
      reorganization in the brain, including changes in receptive fields. However, when
      or how the remodeling occurs is largely unknown. Here we show the rapid rewiring
      of afferent fibers in the mature ventral posteromedial thalamic nucleus of mice
      after transection of the peripheral whisker sensory nerve, using the whole-cell
      voltage-clamp technique. Transection induced the recruitment of afferent fibers
      to a thalamic relay neuron within 5-6 d of injury. The rewiring was pathway
      specific, but not sensory experience dependent or peripheral nerve activity
      dependent. The newly recruited fibers mediated small EPSCs, and postsynaptic
      GluA2-containing AMPA receptors were selectively upregulated at the new synapses.
      This rapid and pathway-specific remodeling of thalamic circuitry may be an
      initial step in the massive axonal reorganization at supraspinal levels, which
      occurs months or years after peripheral sensory nerve injury.

PMID- 22593061
TI  - Rab3A mediates vesicle delivery at photoreceptor ribbon synapses.
AB  - Rab3A is a synaptic vesicle-associated protein found throughout the nervous
      system, but its precise function is unknown. Genetic knock-out studies show that
      Rab3A is not necessary for vesicular release or replenishment at conventional
      synapses in the brain. Here we explore the function of Rab3A at ribbon synapses
      in the retina of the tiger salamander (Ambystoma tigrinum). Fluorescently labeled
      Rab3A, delivered into rods and cones through a patch pipette, binds to and
      dissociates from synaptic ribbons. Experiments using nonphosphorylatable GDP
      analogs and a GTPase-deficient Rab3A mutant indicate that ribbon binding and
      dissociation are governed by a GTP hydrolysis cycle. Paired recordings from
      presynaptic photoreceptors and postsynaptic OFF-bipolar cells show that the Rab3A
      mutant blocks synaptic release in an activity-dependent manner, with more
      frequent stimulation leading to more rapid block. The frequency dependence of
      block by exogenous Rab3A suggests that it acts competitively with synaptic
      vesicles to interfere with their resupply to release sites. Together, these
      findings suggest a crucial role of Rab3A in delivering vesicles to Ca2+-dependent
      release sites at ribbon synapses.

PMID- 22593062
TI  - Sleep deprivation is associated with attenuated parametric valuation and control
      signals in the midbrain during value-based decision making.
AB  - Sleep deprivation (SD) has detrimental effects on cognition, but the affected
      psychological processes and underlying neural mechanisms are still essentially
      unclear. Here we combined functional magnetic resonance imaging and computational
      modeling to examine how SD alters neural representation of specific choice
      variables (subjective value and decision conflict) during reward-related decision
      making. Twenty-two human subjects underwent two functional neuroimaging sessions
      in counterbalanced order, once during rested wakefulness and once after 24 h of
      SD. Behaviorally, SD attenuated conflict-dependent slowing of response times,
      which was reflected in an attenuated conflict-induced decrease in drift rates in
      the drift diffusion model. Furthermore, SD increased overall choice stochasticity
      during risky choice. Model-based functional neuroimaging revealed attenuated
      parametric subjective value signals in the midbrain, parietal cortex, and
      ventromedial prefrontal cortex after SD. Conflict-related midbrain signals showed
      a similar downregulation. Findings are discussed with respect to changes in
      dopaminergic signaling associated with the sleep-deprived state.

PMID- 22593063
TI  - Spatiotemporal changes to the subventricular zone stem cell pool through aging.
AB  - Through adulthood, the rodent subventricular zone (SVZ) stem cell niche generates
      new olfactory bulb interneurons. We had previously reported that the number of
      new neurons produced in the SVZ declines through aging; however, age-related
      changes attributable specifically to the SVZ neural stem cell (NSC) population
      have not been fully characterized. Here, we conducted a spatiotemporal evaluation
      of adult SVZ NSCs. We assessed ventricle-contacting NSCs, which together with
      ependymal cells form regenerative units (pinwheels) along the lateral wall of the
      lateral ventricle. Based on their apical GFAP-expressing process, individual NSCs
      were identified across the ventricle surface using serial reconstruction of the
      SVZ. We observed an 86% decline in total NSCs/mm2 of intact ependyma in 2-year
      old versus 3-month-old mice, with fewer NSC processes within each aged pinwheel.
      This resulted in an associated 78% decline in total pinwheel units/mm2. Regional
      analysis along the lateral ventricle surface revealed that the age-dependent
      decline of NSCs and pinwheels is spatially uniform and ultimately maintains the
      conserved ratio of olfactory bulb interneuron subtypes generated in young mice.
      However, the overall neurogenic output of the aged SVZ is reduced. Surprisingly,
      we found no significant change in the number of actively proliferating NSCs per
      mm2 of ventricle surface. Instead, our data reveal that, although the total NSC
      number, pinwheel units and NSCs per pinwheel decline with age, the percentage of
      actively, mitotic NSCs increases, indicating that age-related declines in SVZ
      mediated olfactory bulb neurogenesis occur downstream of NSC proliferation.

PMID- 22593064
TI  - Subregional, dendritic compartment, and spine subtype specificity in cocaine
      regulation of dendritic spines in the nucleus accumbens.
AB  - Numerous studies have found that chronic cocaine increases dendritic spine
      density of medium spiny neurons in the nucleus accumbens (NAc). Here, we used
      single-cell microinjections and advanced 3D imaging and analysis techniques to
      extend these findings in several important ways: by assessing cocaine regulation
      of dendritic spines in the core versus shell subregions of NAc in the mouse, over
      a broad time course (4 h, 24 h, or 28 d) of withdrawal from chronic cocaine, and
      with a particular focus on proximal versus distal dendrites. Our data demonstrate
      subregion-specific, and in some cases opposite, regulation of spines by cocaine
      on proximal but not distal dendrites. Notably, all observed density changes were
      attributable to selective regulation of thin spines. At 4 h after injection, the
      proximal spine density is unchanged in the core but significantly increased in
      the shell. At 24 h, the density of proximal dendritic spines is reduced in the
      core but increased in the shell. Such downregulation of thin spines in the core
      persists through 28 d of withdrawal, whereas the spine density in the shell
      returns to baseline levels. Consistent with previous results, dendritic tips
      exhibited upregulation of dendritic spines after 24 h of withdrawal, an effect
      localized to the shell. The divergence in regulation of proximal spine density in
      NAc core versus shell by cocaine correlates with recently reported
      electrophysiological data from a similar drug administration regimen and might
      represent a key mediator of changes in the reward circuit that drive aspects of
      addiction.

PMID- 22593066
TI  - Light-driven calcium signals in mouse cone photoreceptors.
AB  - Calcium mediates various neuronal functions. The complexity of neuronal Ca2+
      signaling is well exemplified by retinal cone photoreceptors, which, with their
      distinct compartmentalization, offer unique possibilities for studying the
      diversity of Ca2+ functions in a single cell. Measuring subcellular Ca2+ signals
      in cones under physiological conditions is not only fundamental for understanding
      cone function, it also bears important insights into pathophysiological processes
      governing retinal neurodegeneration. However, due to the proximity of light
      sensitive outer segments to other cellular compartments, optical measurements of
      light-evoked Ca2+ responses in cones are challenging. We addressed this problem
      by generating a transgenic mouse (HR2.1:TN-XL) in which both short- and middle
      wavelength-sensitive cones selectively express the genetically encoded
      ratiometric Ca2+ biosensor TN-XL. We show that HR2.1:TN-XL allows recording of
      light-evoked Ca2+ responses using two-photon imaging in individual cone
      photoreceptor terminals and to probe phototransduction and its diverse regulatory
      mechanisms with pharmacology at subcellular resolution. To further test this
      system, we asked whether the classical, nitric oxide (NO)-soluble guanylyl
      cyclase (sGC)-cGMP pathway could modulate Ca2+ in cone terminals. Surprisingly,
      NO reduced Ca2+ resting levels in mouse cones, without evidence for direct sGC
      involvement. In conclusion, HR2.1:TN-XL mice offer unprecedented opportunities to
      elucidate light-driven Ca2+ dynamics and their (dys)regulation in cone
      photoreceptors.

PMID- 22593065
TI  - S-SCAM/MAGI-2 is an essential synaptic scaffolding molecule for the GluA2
      containing maintenance pool of AMPA receptors.
AB  - Synaptic plasticity, the cellular basis of learning and memory, involves the
      dynamic trafficking of AMPA receptors (AMPARs) into and out of synapses. One of
      the remaining key unanswered aspects of AMPAR trafficking is the mechanism by
      which synaptic strength is preserved despite protein turnover. In particular, the
      identity of AMPAR scaffolding molecule(s) involved in the maintenance of GluA2
      containing AMPARs is completely unknown. Here we report that the synaptic
      scaffolding molecule (S-SCAM; also called membrane-associated guanylate kinase
      inverted-2 and atrophin interacting protein-1) plays the critical role of
      maintaining synaptic strength. Increasing S-SCAM levels in rat hippocampal
      neurons led to specific increases in the surface AMPAR levels, enhanced AMPAR
      mediated synaptic transmission, and enlargement of dendritic spines, without
      significantly effecting GluN levels or NMDA receptor (NMDAR) EPSC. Conversely,
      decreasing S-SCAM levels by RNA interference-mediated knockdown caused the loss
      of synaptic AMPARs, which was followed by a severe reduction in the dendritic
      spine density. Importantly, S-SCAM regulated synaptic AMPAR levels in a manner,
      dependent on GluA2 not GluA1, sensitive to N-ethylmaleimide-sensitive fusion
      protein interaction, and independent of activity. Further, S-SCAM increased
      surface AMPAR levels in the absence of PSD-95, while PSD-95 was dependent on S
      SCAM to increase surface AMPAR levels. Finally, S-SCAM overexpression hampered
      NMDA-induced internalization of AMPARs and prevented the induction of long term
      depression, while S-SCAM knockdown did not. Together, these results suggest that
      S-SCAM is an essential AMPAR scaffolding molecule for the GluA2-containing pool
      of AMPARs, which are involved in the constitutive pathway of maintaining synaptic
      strength.

PMID- 22593067
TI  - PGC-1alpha negatively regulates extrasynaptic NMDAR activity and excitotoxicity.
AB  - Underexpression of the transcriptional coactivator PGC-1alpha is causally linked
      to certain neurodegenerative disorders, including Huntington's Disease (HD). HD
      pathoprogression is also associated with aberrant NMDAR activity, in particular
      an imbalance between synaptic versus extrasynaptic (NMDAR(EX)) activity. Here we
      show that PGC-1alpha controls NMDAR(EX) activity in neurons and that its
      suppression contributes to mutant Huntingtin (mHtt)-induced increases in
      NMDAR(EX) activity and vulnerability to excitotoxic insults. We found that knock
      down of endogenous PGC-1alpha increased NMDAR(EX) activity and vulnerability to
      excitotoxic insults in rat cortical neurons. In contrast, exogenous expression of
      PGC-1alpha resulted in a neuroprotective reduction of NMDAR(EX) currents without
      affecting synaptic NMDAR activity. Since HD models are associated with mHtt
      mediated suppression of PGC-1alpha expression, as well as increased NMDAR(EX)
      activity, we investigated whether these two events were linked. Expression of
      mHtt (148Q) resulted in a selective increase in NMDAR(EX) activity, compared with
      wild-type Htt (18Q), and increased vulnerability to NMDA excitotoxicity.
      Importantly, we observed that the effects of mHtt and PGC-1alpha knockdown on
      NMDAR(EX) activity and vulnerability to excitotoxicity were nonadditive and
      occluded each other, consistent with a common mechanism. Moreover, exogenous
      expression of PGC-1alpha reversed mtHtt-mediated increases in NMDAR(EX) activity
      and protected neurons against excitotoxic cell death. The link between mHtt, PGC
      1alpha, and NMDAR activity was also confirmed in rat striatal neurons. Thus,
      targeting levels of PGC-1alpha expression may help reduce aberrant NMDAR(EX)
      activity in disorders where PGC-1alpha is underexpressed.

PMID- 22593068
TI  - Visual attentional load influences plasticity in the human motor cortex.
AB  - Neural plasticity plays a critical role in learning, memory, and recovery from
      injury to the nervous system. Although much is known about the physical and
      physiological determinants of plasticity, little is known about the influence of
      cognitive factors. In this study, we investigated whether selective attention
      plays a role in modifying changes in neural excitability reflecting long-term
      potentiation (LTP)-like plasticity. We induced LTP-like effects in the hand area
      of the human motor cortex using transcranial magnetic stimulation (TMS). During
      the induction of plasticity, participants engaged in a visual detection task with
      either low or high attentional demands. Changes in neural excitability were
      assessed by measuring motor-evoked potentials in a small hand muscle before and
      after the TMS procedures. In separate experiments plasticity was induced either
      by paired associative stimulation (PAS) or intermittent theta-burst stimulation
      (iTBS). Because these procedures induce different forms of LTP-like effects, they
      allowed us to investigate the generality of any attentional influence on
      plasticity. In both experiments reliable changes in motor cortex excitability
      were evident under low-load conditions, but this effect was eliminated under high
      attentional load. In a third experiment we investigated whether the attentional
      task was associated with ongoing changes in the excitability of motor cortex, but
      found no difference in evoked potentials across the levels of attentional load.
      Our findings indicate that in addition to their role in modifying sensory
      processing, mechanisms of attention can also be a potent modulator of cortical
      plasticity.

PMID- 22593069
TI  - Approach-avoidance processes contribute to dissociable impacts of risk and loss
      on choice.
AB  - Value-based choices are influenced both by risk in potential outcomes and by
      whether outcomes reflect potential gains or losses. These variables are held to
      be related in a specific fashion, manifest in risk aversion for gains and risk
      seeking for losses. Instead, we hypothesized that there are independent impacts
      of risk and loss on choice such that, depending on context, subjects can show
      either risk aversion for gains and risk seeking for losses or the exact opposite.
      We demonstrate this independence in a gambling task, by selectively reversing a
      loss-induced effect (causing more gambling for gains than losses and the reverse)
      while leaving risk aversion unaffected. Consistent with these dissociable
      behavioral impacts of risk and loss, fMRI data revealed dissociable neural
      correlates of these variables, with parietal cortex tracking risk and
      orbitofrontal cortex and striatum tracking loss. Based on our neural data, we
      hypothesized that risk and loss influence action selection through approach
      avoidance mechanisms, a hypothesis supported in an experiment in which we show
      valence and risk-dependent reaction time effects in line with this putative
      mechanism. We suggest that in the choice process risk and loss can independently
      engage approach-avoidance mechanisms. This can provide a novel explanation for
      how risk influences action selection and explains both classically described
      choice behavior as well as behavioral patterns not predicted by existing theory.

PMID- 22593070
TI  - Laminarly orthogonal excitation of fast-spiking and low-threshold-spiking
      interneurons in mouse motor cortex.
AB  - In motor cortex, long-range output to subcortical motor circuits depends on
      excitatory and inhibitory inputs converging on projection neurons in layers 5A/B.
      How interneurons interconnect with these projection neurons, and whether these
      microcircuits are interneuron and/or projection specific, is unclear. We found
      that fast-spiking interneurons received strong intralaminar (horizontal)
      excitation from pyramidal neurons in layers 5A/B including corticostriatal and
      corticospinal neurons, implicating them in mediating disynaptic recurrent,
      feedforward, and feedback inhibition within and across the two projection
      classes. Low-threshold-spiking (LTS) interneurons were instead strongly excited
      by descending interlaminar (vertical) input from layer 2/3 pyramidal neurons,
      implicating them in mediating disynaptic feedforward inhibition to both
      projection classes. Furthermore, in a novel pattern, lower layer 2/3
      preferentially excited interneurons in one layer (5A/LTS) and excitatory neurons
      in another (5B/corticospinal). Thus, these inhibitory microcircuits in mouse
      motor cortex follow an orderly arrangement that is laminarly orthogonalized by
      interneuron-specific, projection-nonspecific connectivity.

PMID- 22593071
TI  - Pre-cue fronto-occipital alpha phase and distributed cortical oscillations
      predict failures of cognitive control.
AB  - Cognitive control is required for correct performance on antisaccade tasks,
      including the ability to inhibit an externally driven ocular motor response (a
      saccade to a peripheral stimulus) in favor of an internally driven ocular motor
      goal (a saccade directed away from a peripheral stimulus). Healthy humans
      occasionally produce errors during antisaccade tasks, but the mechanisms
      associated with such failures of cognitive control are uncertain. Most research
      on cognitive control failures focuses on poststimulus processing, although a
      growing body of literature highlights a role of intrinsic brain activity in
      perceptual and cognitive performance. The current investigation used dense array
      electroencephalography and distributed source analyses to examine brain
      oscillations across a wide frequency bandwidth in the period before antisaccade
      cue onset. Results highlight four important aspects of ongoing and preparatory
      brain activations that differentiate error from correct antisaccade trials: (1)
      ongoing oscillatory beta (20-30 Hz) power in anterior cingulate before trial
      initiation (lower for error trials); (2) instantaneous phase of ongoing
      alpha/theta (7 Hz) in frontal and occipital cortices immediately before trial
      initiation (opposite between trial types); (3) gamma power (35-60 Hz) in
      posterior parietal cortex 100 ms before cue onset (greater for error trials); and
      (4) phase locking of alpha (5-12 Hz) in parietal and occipital cortices
      immediately before cue onset (lower for error trials). These findings extend
      recently reported effects of pre-trial alpha phase on perception to cognitive
      control processes and help identify the cortical generators of such phase
      effects.

PMID- 22593072
TI  - PKC-2 phosphorylation of UNC-18 Ser322 in AFD neurons regulates temperature
      dependency of locomotion.
AB  - Diacylglycerol (DAG)/protein kinase C (PKC) signaling plays an integral role in
      the regulation of neuronal function. This is certainly true in Caenorhabditis
      elegans and in particular for thermosensory signaling and behavior. Downstream
      molecular targets for transduction of this signaling cascade remain, however,
      virtually uncharacterized. We investigated whether PKC phosphorylation of Munc18
      1, an essential protein in vesicle trafficking and exocytosis, was the downstream
      effector for DAG regulation of thermosensory behavior. We demonstrate here that
      the C. elegans ortholog of Munc18-1, UNC-18, was phosphorylated in vitro at
      Ser322. Transgenic rescue of unc-18-null worms with Ser322 phosphomutants
      displayed altered thermosensitivity. C. elegans expresses three DAG-regulated
      PKCs, and blocking UNC-18 Ser322 phosphorylation was phenocopied only by deletion
      of calcium-activated PKC-2. Expression of nonphosphorylatable UNC-18 S322A,
      either pan-neuronally or specifically in AFD thermosensory neurons, converted
      wild-type worms to a pkc-2-null phenotype. These data demonstrate that an
      individual DAG-dependent thermosensory behavior of an organism is effected
      specifically by the downstream PKC-2 phosphorylation of UNC-18 on Ser322 in AFD
      neurons.

PMID- 22593073
TI  - Adult neurogenesis is associated with the maintenance of a stereotyped, learned
      motor behavior.
AB  - Adult neurogenesis is thought to provide neural plasticity used in forming and
      storing new memories. Here we show a novel relationship between numbers of new
      neurons and the stability of a previously learned motor pattern. In the adult
      zebra finch, new projection neurons are added to the nucleus HVC and become part
      of the motor pathway for producing learned song. However, new song learning
      occurs only in juveniles and the behavioral impact of adding new neurons to HVC
      throughout life is unclear. We report that song changes after deafening are
      inversely correlated with the number of new neurons added to HVC, suggesting that
      adult neurogenesis in this context may contribute to behavioral stability. More
      broadly, we propose that new neuron function may depend on the site of
      integration and can vary as widely as promoting, or restricting, behavioral
      plasticity.

PMID- 22593074
TI  - Regulation of Fasciclin II and synaptic terminal development by the splicing
      factor beag.
AB  - Pre-mRNA alternative splicing is an important mechanism for the generation of
      synaptic protein diversity, but few factors governing this process have been
      identified. From a screen for Drosophila mutants with aberrant synaptic
      development, we identified beag, a mutant with fewer synaptic boutons and
      decreased neurotransmitter release. Beag encodes a spliceosomal protein similar
      to splicing factors in humans and Caenorhabditis elegans. We find that both beag
      mutants and mutants of an interacting gene dsmu1 have changes in the synaptic
      levels of specific splice isoforms of Fasciclin II (FasII), the Drosophila
      ortholog of neural cell adhesion molecule. We show that restoration of one splice
      isoform of FasII can rescue synaptic morphology in beag mutants while expression
      of other isoforms cannot. We further demonstrate that this FasII isoform has
      unique functions in synaptic development independent of transsynaptic adhesion.
      beag and dsmu1 mutants demonstrate an essential role for these previously
      uncharacterized splicing factors in the regulation of synapse development and
      function.

PMID- 22593075
TI  - Brain-derived neurotrophic factor Val66Met polymorphism affects resting regional
      cerebral blood flow and functional connectivity differentially in women versus
      men.
AB  - The human Val66Met single nucleotide polymorphism in the brain-derived
      neurotrophic factor (BDNF) gene impacts BDNF signaling at the cellular level. At
      the neural-systems level, it is associated with differences in prefrontal cortex
      (PFC) and hippocampal function during performance of cognitive and affective
      tasks. Because the impact of this variant on basal prefrontal and hippocampal
      activity is not known but may be relevant to understanding the function of this
      gene in health and disease, we studied 94 healthy individuals with H2 15O PET to
      assess regional cerebral blood flow (rCBF) during rest and tested for between
      genotype differences. Because BDNF and gonadal steroid hormones conjointly
      influence neuronal growth, survival, and plasticity in hippocampus and PFC, we
      also tested for sex * genotype interactions. Finally, in light of the known
      impact of BDNF on plasticity and dendritic arborization, we complimented direct
      rCBF comparisons with connectivity analyses to determine how activity in
      hippocampal and prefrontal regions showing between-genotype group differences
      covaries with rCBF in other nodes throughout the brain in a genotype- or sex
      dependent manner. Compared with Val homozygotes, Met carriers had higher rCBF in
      prefrontal (BA25 extending into BA10) and hippocampal/parahippocampal regions.
      Moreover, there were significant sex * genotype interactions in regions
      (including frontal, parahippocampal, and lateral temporal cortex) in which Val
      homozygotes showed higher rCBF in females than males, but Met carriers showed the
      opposite relationship. Functional connectivity analysis demonstrated that
      correlations of BA25, hippocampus, and parahippocampus with frontal and temporal
      networks were positive for Val homozygotes and negative for Met carriers. In
      addition, sex * genotype analysis of functional connectivity revealed that
      genotype affected directionality of the inter-regional correlations
      differentially in men versus women. Our data indicate that BDNF allelic variation
      and sex interactively affect basal prefrontal and hippocampal function.

PMID- 22593076
TI  - Connectivity changes underlying spectral EEG changes during propofol-induced loss
      of consciousness.
AB  - The mechanisms underlying anesthesia-induced loss of consciousness remain a
      matter of debate. Recent electrophysiological reports suggest that while initial
      propofol infusion provokes an increase in fast rhythms (from beta to gamma
      range), slow activity (from delta to alpha range) rises selectively during loss
      of consciousness. Dynamic causal modeling was used to investigate the neural
      mechanisms mediating these changes in spectral power in humans. We analyzed
      source-reconstructed data from frontal and parietal cortices during normal
      wakefulness, propofol-induced mild sedation, and loss of consciousness. Bayesian
      model selection revealed that the best model for explaining spectral changes
      across the three states involved changes in corticothalamic interactions.
      Compared with wakefulness, mild sedation was accounted for by an increase in
      thalamic excitability, which did not further increase during loss of
      consciousness. In contrast, loss of consciousness per se was accompanied by a
      decrease in backward corticocortical connectivity from frontal to parietal
      cortices, while thalamocortical connectivity remained unchanged. These results
      emphasize the importance of recurrent corticocortical communication in the
      maintenance of consciousness and suggest a direct effect of propofol on cortical
      dynamics.

PMID- 22593078
TI  - Wintersweet-flower-like CoFe2O4/MWCNTs hybrid material for high-capacity
      reversible lithium storage.
AB  - CoFe(2)O(4)/multiwalled carbon nanotubes (MWCNTs) hybrid materials were
      synthesized by a hydrothermal method. Field emission scanning electron microscopy
      and transmission electron microscopy analysis confirmed the morphology of the as
      prepared hybrid material resembling wintersweet flower "buds on branches", in
      which CoFe(2)O(4) nanoclusters, consisting of nanocrystals with a size of 5-10
      nm, are anchored along carbon nanotubes. When applied as an anode material in
      lithium ion batteries, the CoFe(2)O(4)/MWCNTs hybrid material exhibited a high
      performance for reversible lithium storage. In particular, the hybrid anode
      material delivered reversible lithium storage capacities of 809, 765, 539, and
      359 mA h g(-1) at current densities of 180, 450, 900, and 1800 mA g(-1),
      respectively. The superior performance of CoFe(2)O(4)/MWCNTs hybrid materials
      could be ascribed to the synergistic pinning effect of the wintersweet-flower
      like nanoarchitecture. This strategy could also be applied to synthesize other
      metal oxide/CNTs hybrid materials as high-capacity anode materials for lithium
      ion batteries.

PMID- 22593077
TI  - Cannabinoid type-1 receptor reduces pain and neurotoxicity produced by
      chemotherapy.
AB  - Painful peripheral neuropathy is a dose-limiting complication of chemotherapy.
      Cisplatin produces a cumulative toxic effect on peripheral nerves, and 30-40% of
      cancer patients receiving this agent experience pain. By modeling cisplatin
      induced hyperalgesia in mice with daily injections of cisplatin (1 mg/kg, i.p.)
      for 7 d, we investigated the anti-hyperalgesic effects of anandamide (AEA) and
      cyclohexylcarbamic acid 3'-carbamoyl-biphenyl-3-yl ester (URB597), an inhibitor
      of AEA hydrolysis. Cisplatin-induced mechanical and heat hyperalgesia were
      accompanied by a decrease in the level of AEA in plantar paw skin. No changes in
      motor activity were observed after seven injections of cisplatin. Intraplantar
      injection of AEA (10 MUg/10 MUl) or URB597 (9 MUg/10 MUl) transiently attenuated
      hyperalgesia through activation of peripheral CB1 receptors. Co-injections of
      URB597 (0.3 mg/kg daily, i.p.) with cisplatin decreased and delayed the
      development of mechanical and heat hyperalgesia. The effect of URB597 was
      mediated by CB1 receptors since AM281 (0.33 mg/kg daily, i.p.) blocked the effect
      of URB597. Co-injection of URB597 also normalized the cisplatin-induced decrease
      in conduction velocity of Aalpha/Abeta-fibers and reduced the increase of ATF-3
      and TRPV1 immunoreactivity in dorsal root ganglion (DRG) neurons. Since DRGs are
      a primary site of toxicity by cisplatin, effects of cisplatin were studied on
      cultured DRG neurons. Incubation of DRG neurons with cisplatin (4 MUg/ml) for 24
      h decreased the total length of neurites. URB597 (100 nM) attenuated these
      changes through activation of CB1 receptors. Collectively, these results suggest
      that pharmacological facilitation of AEA signaling is a promising strategy for
      attenuating cisplatin-associated sensory neuropathy.

PMID- 22593079
TI  - Consequences of cooperativity in racemizing supramolecular systems.
AB  - Saluting the sergeant: Phg-BTA (see scheme) cooperatively self-assembles into
      helical aggregates and shows unprecedented racemization behavior in the presence
      of base. In thermodynamically controlled conditions, the addition of a small
      amount of chiral auxiliary to this mixture results in a deracemization reaction
      and a final enantiomeric excess of 32 %. A theoretical model is presented to
      understand in detail the results obtained.

PMID- 22593080
TI  - Juvenile, but not adult exposure to high-fat diet impairs relational memory and
      hippocampal neurogenesis in mice.
AB  - Increased consumption of high-fat diet (HFD) leads to obesity and adverse
      neurocognitive outcomes. Childhood and adolescence are important periods of brain
      maturation shaping cognitive function. These periods could consequently be
      particularly sensitive to the detrimental effects of HFD intake. In mice,
      juvenile and adulthood consumption of HFD induce similar morphometric and
      metabolic changes. However, only juvenile exposure to HFD abolishes relational
      memory flexibility, assessed after initial radial-maze concurrent spatial
      discrimination learning, and decreases neurogenesis. Our results identify a
      critical period of development covering adolescence with higher sensitivity to
      HFD-induced hippocampal dysfunction at both behavioral and cellular levels.

PMID- 22593081
TI  - Fetal gyrification in cynomolgus monkeys: a concept of developmental stages of
      gyrification.
AB  - Our article summarizes a series of studies about fetal gyrification and its
      relation to cerebral growth in cynomolgus monkeys. Based on the cerebral growth
      (i.e., brain weight, cerebral volume, and frontooccipital length of the cerebral
      hemisphere) and the developmental pattern of gyrification in each sulcus of
      cynomolgus monkeys, we divided the gyrification process into four stages: Stage
      1. Demarcation of cerebral lobes and limbic gyri; Stage 2. Demarcation of
      neocortical gyri; Stage 3. Emergence of secondary and tertiary sulci; and Stage
      4. Growth of sulcal length and depth. Each stage of those gyrification processes
      was influenced by different developmental events, such as the emergence of
      corticocortical long-associative fiber tracts, cortical maturations, and
      subcortical white-matter development. This is the first report to systematically
      propose gyrification processes closely related to the order of phyologenetical
      development of the cerebral cortex in primates.

PMID- 22593083
TI  - Gold-catalyzed cascade cyclizations of 1,6-diynyl carbonates to benzo[b]fluorenes
      involving arylation of oxocarbenium ion intermediates and decarboxylative
      etherification.
AB  - Rearranged: The described gold-catalyzed cycloisomerizations give access to
      highly substituted benzo[b]fluorenes under mild reaction conditions (see scheme).
      Experimental results indicate that the in situ formed oxocarbenium ion
      intermediates, derived from gold-catalyzed 3,3-rearrangement and 6-endo-dig
      cyclization, undergo intramolecular arylation and subsequent decarboxylative
      etherification to furnish the final ether products.

PMID- 22593082
TI  - Progesterone promotes focal adhesion formation and migration in breast cancer
      cells through induction of protease-activated receptor-1.
AB  - Progesterone and progestins have been demonstrated to enhance breast cancer cell
      migration, although the mechanisms are still not fully understood. The protease
      activated receptors (PARs) are a family of membrane receptors that are activated
      by serine proteases in the blood coagulation cascade. PAR1 (F2R) has been
      reported to be involved in cancer cell migration and overexpressed in breast
      cancer. We herein demonstrate that PAR1 mRNA and protein are upregulated by
      progesterone treatment of the breast cancer cell lines ZR-75 and T47D. This
      regulation is dependent on the progesterone receptor (PR) but does not require PR
      phosphorylation at serine 294 or the PR proline-rich region mPRO. The increase in
      PAR1 mRNA was transient, being present at 3  h and returning to basal levels at
      18  h. The addition of a PAR1-activating peptide (aPAR1) to cells treated with
      progesterone resulted in an increase in focal adhesion (FA) formation as measured
      by the cellular levels of phosphorylated FA kinase. The combined but not
      individual treatment of progesterone and aPAR1 also markedly increased stress
      fiber formation and the migratory capacity of breast cancer cells. In agreement
      with in vitro findings, data mining from the Oncomine platform revealed that PAR1
      expression was significantly upregulated in PR-positive breast tumors. Our
      observation that PAR1 expression and signal transduction are modulated by
      progesterone provides new insight into how the progestin component in hormone
      therapies increases the risk of breast cancer in postmenopausal women.

PMID- 22593084
TI  - Dorsal hippocampus is necessary for novel learning but sufficient for subsequent
      similar learning.
AB  - Our current understanding of brain mechanisms involved in learning and memory has
      been derived largely from studies using experimentally naive animals. However, it
      is becoming increasingly clear that not all identified mechanisms may generalize
      to subsequent learning. For example, N-methyl-D-aspartate glutamate (NMDA)
      receptors in the dorsal hippocampus are required for contextual fear conditioning
      in naive animals but not in animals previously trained in a similar task. Here we
      investigated how animals learn contextual fear conditioning for a second time-a
      response which is not due to habituation or generalization. We found that dorsal
      hippocampus infusions of voltage-dependent calcium channel blockers or the
      inhibitory neurotransmitter gamma-aminobutyric acid (GABA) agonist impaired the
      first, not the second contextual learning. Only manipulations of the entire
      hippocampus led to an impairment in second learning. Specifically, inactivation
      of either the dorsal or ventral hippocampus caused the remaining portion of the
      hippocampus to acquire and consolidate the second learning. Thus, dorsal
      hippocampus seems necessary for initial contextual fear conditioning, but either
      the dorsal or ventral hippocampus is sufficient for subsequent conditioning in a
      different context. Together, these findings suggest that prior training
      experiences can change how the hippocampus processes subsequent similar learning.

PMID- 22593085
TI  - Flight responses by a migratory soaring raptor to changing meteorological
      conditions.
AB  - Soaring birds that undertake long-distance migration should develop strategies to
      minimize the energetic costs of endurance flight. This is relevant because
      condition upon completion of migration has direct consequences for fecundity,
      fitness and thus, demography. Therefore, strong evolutionary pressures are
      expected for energy minimization tactics linked to weather and topography.
      Importantly, the minute-by-minute mechanisms birds use to subsidize migration in
      variable weather are largely unknown, in large part because of the technological
      limitations in studying detailed long-distance bird flight. Here, we show golden
      eagle (Aquila chrysaetos) migratory response to changing meteorological
      conditions as monitored by high-resolution telemetry. In contrast to
      expectations, responses to meteorological variability were stereotyped across the
      10 individuals studied. Eagles reacted to increased wind speed by using more
      orographic lift and less thermal lift. Concomitantly, as use of thermals
      decreased, variation in flight speed and altitude also decreased. These results
      demonstrate how soaring migrant birds can minimize energetic expenditures, they
      show the context for avian decisions and choices of specific instantaneous flight
      mechanisms and they have important implications for design of bird-friendly wind
      energy.

PMID- 22593086
TI  - More than 1000 ultraconserved elements provide evidence that turtles are the
      sister group of archosaurs.
AB  - We present the first genomic-scale analysis addressing the phylogenetic position
      of turtles, using over 1000 loci from representatives of all major reptile
      lineages including tuatara. Previously, studies of morphological traits
      positioned turtles either at the base of the reptile tree or with lizards, snakes
      and tuatara (lepidosaurs), whereas molecular analyses typically allied turtles
      with crocodiles and birds (archosaurs). A recent analysis of shared microRNA
      families found that turtles are more closely related to lepidosaurs. To test this
      hypothesis with data from many single-copy nuclear loci dispersed throughout the
      genome, we used sequence capture, high-throughput sequencing and published
      genomes to obtain sequences from 1145 ultraconserved elements (UCEs) and their
      variable flanking DNA. The resulting phylogeny provides overwhelming support for
      the hypothesis that turtles evolved from a common ancestor of birds and
      crocodilians, rejecting the hypothesized relationship between turtles and
      lepidosaurs.

PMID- 22593087
TI  - Splenectomy delays uterine natural killer cell recruitment to implantation sites
      and prolongs pregnancy in mice.
AB  - Uterine natural killer (uNK) cells are the dominant lymphocytes found in pregnant
      mammals that develop uterine decidualization. Four stages of mouse uNK cell
      differentiation are recognized using Dolichos biflorus agglutinin (DBA) lectin
      histochemistry. Each uNK cell subtype has a preferential domain. In human and
      mouse normal pregnancies, uNK cells are activated interferon gamma-producing
      cells that promote angiogenesis and development of the decidua and placenta.
      Murine transplant models suggest that uNK cells differentiate from self-renewing
      progenitors found in peripheral secondary lymphoid tissues, particularly spleen
      and lymph nodes. In this work, the spleen was removed 7 days before mice were
      mated to address whether absence of the spleen reduced uNK cell numbers or
      altered the distributions of maturing uNK cell subsets using quantitative lectin
      histochemistry. Splenectomy delayed uNK cell maturation within implantation
      sites. This coincided with delayed decidual and placental development and a
      significant (48 hr) lengthening of gestation without loss of viability. These
      studies characterize spleen as a biologically important progenitor tissue for uNK
      precursor cells.

PMID- 22593088
TI  - A simple and fast method for profiling microRNA expression from low-input total
      RNA by microarray.
AB  - Analysis of mature microRNA (miRNA) expression is important to understand its
      physiological functions and pathological implications. Microarray is a powerful
      technology to profile global miRNA expression. In this study, we developed a
      rapid miRNA labeling method by which miRNA was directly labeled in total RNA for
      microarray detection. This method consists of RNA tailing by poly(A) polymerase,
      reverse transcription, and template-switching by moloney murine leukemia virus
      (MMLV) reverse transcriptase. After these reactions, the small RNA cDNA was ready
      for labeling for microarray detection. The whole process of prearray sample
      preparation was dramatically shortened to 2 h. Furthermore, this method allows
      very limited starting total RNA (100 ng) for microarray analysis. Our data showed
      that the results from our method were highly consistent with that of real-time
      polymerase chain reaction (PCR).

PMID- 22593089
TI  - Divergence between oculomotor and perceptual causality.
AB  - When two objects such as billiard balls collide, observers perceive that the
      action of one caused the motion of the other. We have previously shown (Badler,
      Lefevre, & Missal, 2010) that this extends to the oculomotor domain: subjects
      make more predictive movements in the expected direction of causal motion than in
      a noncausal direction. However, predictive oculomotor and reactive psychophysical
      responses have never been directly compared. They should be correlated if they
      tap into the same mental processes. To test this, we recorded oculomotor
      responses to launching stimuli, then asked subjects to manually classify those
      stimuli as causal or noncausal. Overall the psychophysical classifications
      matched the oculomotor biases, although correlations across subjects were mostly
      absent. In subsequent experiments, 50% of the trials had a 300-millisecond delay
      after the collision to impede the perception of causality. Subjects maintained
      their causal oculomotor bias but used different classification strategies,
      usually grouping the stimuli either by delay or by direction. In addition, there
      was no evidence that the two response types were correlated on a trial-by-trial
      basis. The results suggest divergent processes underlying oculomotor responses to
      and judgments of causal stimuli.

PMID- 22593090
TI  - Shedding light on night myopia.
AB  - First described during the 18th century, the cause of night myopia remains a
      controversial topic. Whereas several explanations have been suggested in the
      literature, particularly related with accommodation or chromatic shift in
      scotopic light conditions, no definitive explanation for its aetiology has been
      provided. We describe an experiment in which ocular refractive state was
      objectively and subjectively measured while viewing two kind of stimulus: letters
      on a bright background and a punctual source of light in a dark background. We
      found that under photopic conditions the optimum refractive state of the
      accommodating eye is significantly more myopic when maximizing perceived quality
      of a point source on a dark background compared to a conventional letter chart
      with black letters on a white background. Optical modeling suggested this
      difference in refractive state is due to spherical aberration. Since isolated
      point sources are more likely encountered at night, whereas extended objects are
      more likely encountered in the daytime, our results suggest that a significant
      part of the night myopia phenomenon is determined by the nature of the visual
      stimulus and the visual task used to assess ocular refractive state.

PMID- 22593091
TI  - Individualized anterior cruciate ligament surgery: a prospective study comparing
      anatomic single- and double-bundle reconstruction.
AB  - BACKGROUND: Reconstruction of the anterior cruciate ligament (ACL) has become a
      commonly performed procedure. However, biomechanical studies have demonstrated
      that conventional single-bundle ACL reconstruction techniques are only successful
      in limiting anterior tibial translation but less effective for restoring rotatory
      laxity. PURPOSE: This study aimed to compare the results of single- and double
      bundle ACL reconstruction using an anatomic technique, individualized based on
      the patient's native ACL size. The authors hypothesized that there would be no
      difference between the results of anatomic single-bundle (ASB) and anatomic
      double-bundle (ADB) reconstruction when the surgical technique is individualized.
      STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Depending on
      intraoperative measurements of the ACL insertion site size, patients were
      selected for either ASB (n = 32) or ADB (n = 69) ACL reconstruction. In all
      groups, hamstring tendons autograft was used with suspensory fixation on the
      femoral side and bioabsorbable interference screw fixation on the tibial side.
      The outcomes were evaluated by an independent blinded observer using the Lysholm
      score, subjective International Knee Documentation Committee (IKDC) form, KT-1000
      arthrometer for anteroposterior stability, and pivot-shift test for rotational
      stability. The average follow-up was 30 months (range, 26-34 months). There were
      no statistically significant differences in the baseline demographics of the 2
      groups. RESULTS: There was no significant difference between the ADB and ASB
      groups for Lysholm score (93.9 vs 93.5), subjective IKDC score (93.3 vs 93.1),
      anterior tibial translation (1.5- vs 1.6-mm side-to-side difference), and pivot
      shift (92% vs 90% with negative pivot-shift examination). CONCLUSION: Anatomic
      double-bundle reconstruction is not superior to anatomic single-bundle
      reconstruction when an individualized ACL reconstruction technique is used.

PMID- 22593092
TI  - Deficits in heel-rise height and achilles tendon elongation occur in patients
      recovering from an Achilles tendon rupture.
AB  - BACKGROUND: Whether an Achilles tendon rupture is treated surgically or not,
      complications such as muscle weakness, decrease in heel-rise height, and gait
      abnormalities persist after injury. PURPOSE: The purpose of this study was to
      evaluate if side-to-side differences in maximal heel-rise height can be explained
      by differences in Achilles tendon length. STUDY DESIGN: Case series; level of
      evidence, 4. METHOD: Eight patients (mean [SD] age of 46 [13] years) with acute
      Achilles tendon rupture and 10 healthy subjects (mean [SD] age of 28 [8] years)
      were included in the study. Heel-rise height, Achilles tendon length, and patient
      reported outcome were measured 3, 6, and 12 months after injury. Achilles tendon
      length was evaluated using motion analysis and ultrasound imaging. RESULTS: The
      Achilles tendon length test-retest reliability (intraclass correlation
      coefficient = 0.97) was excellent. For the healthy subjects, there were no side
      to-side differences in tendon length and heel-rise height. Patients with Achilles
      tendon ruptures had significant differences between the injured and uninjured
      side for both tendon length (mean [SD] difference, 2.6-3.1 [1.2-1.4] cm, P = .017
      .028) and heel-rise height (mean [SD] difference, -4.1 to -6.1 [1.7-1.8] cm, P =
      .012-.028). There were significant negative correlations (r = -0.943, P = .002,
      and r = -0.738, P = .037) between the side-to-side difference in heel-rise height
      and Achilles tendon length at the 6- and 12-month evaluations, respectively.
      CONCLUSION: The side-to-side difference found in maximal heel-rise height can be
      explained by a difference in Achilles tendon length in patients recovering from
      an Achilles tendon rupture. Minimizing tendon elongation appears to be an
      important treatment goal when aiming for full return of function.

PMID- 22593093
TI  - An analysis of N-acetylcysteine treatment for acetaminophen overdose using a
      systems model of drug-induced liver injury.
AB  - N-acetylcysteine (NAC) is the treatment of choice for acetaminophen poisoning;
      standard 72-h oral or 21-h intravenous protocols are most frequently used. There
      is controversy regarding which protocol is optimal and whether the full treatment
      course is always necessary. It would be challenging to address these questions in
      a clinical trial. We used DILIsym, a mechanistic simulation of drug-induced liver
      injury, to investigate optimal NAC treatment after a single acetaminophen
      overdose for an average patient and a sample population (n = 957). For patients
      presenting within 24 h of ingestion, we found that the oral NAC protocol
      preserves more hepatocytes than the 21-h intravenous protocol. In various modeled
      scenarios, we found that the 21-h NAC infusion is often too short, whereas the
      full 72-h oral course is often unnecessary. We found that there is generally a
      good correlation between the time taken to reach peak serum alanine
      aminotransferase (ALT) and the time taken to clear N-acetyl-p-benzoquinone imine
      (NAPQI) from the liver. We also found that the most frequently used treatment
      nomograms underestimate the risk for patients presenting within 8 h of overdose
      ingestion. V(max) for acetaminophen bioactivation to NAPQI was the most important
      variable in the model in determining interpatient differences in susceptibility.
      In conclusion, DILIsym predicts that the oral NAC treatment protocol, or an
      intravenous protocol with identical dosing, is superior to the 21-h intravenous
      protocol and ALT is the optimal available biomarker for discontinuation of the
      therapy. The modeling also suggests that modification of the current treatment
      nomograms should be considered.

PMID- 22593094
TI  - Enhancement of MU-opioid receptor desensitization by nitric oxide in rat locus
      coeruleus neurons: involvement of reactive oxygen species.
AB  - It has previously been shown that nitric oxide (NO) synthase is involved in the
      development of opioid tolerance. The aim of the present work was to study the
      effect of NO on MU-opioid receptor (MOR) desensitization. Furthermore, we
      explored the possible role of reactive oxygen species (ROS) in this effect.
      Single-unit extracellular and whole-cell patch-clamp recordings were performed on
      locus coeruleus (LC) neurons from rat brain slices. Perfusion with high
      concentrations of Met(5)-enkephalin (ME) caused a concentration-related reduction
      of opioid effect, reflecting the induction of homologous MOR desensitization. The
      NO donors sodium nitroprusside and diethylamine NONOate markedly enhanced the ME
      induced MOR desensitization, although the acute effect of ME on K(+) conductance
      was not affected by sodium nitroprusside. Continuous perfusion with the
      antioxidants melatonin, trolox, 21-[4-(2,6-di-1-pyrrolidinyl-4-pyrrimidinyl)-1
      piperazinyl]-pregna-1,4,9(11)-triene-3,20-dione(Z)-2-butenedioate (U74389G), and
      diethyldithiocarbamate prevented the effect of sodium nitroprusside on MOR
      desensitization, but they did not themselves alter the desensitization. Like
      sodium nitroprusside, the ROS-generating molecule H(2)O(2) enhanced MOR
      desensitization induced by ME. However, alpha(2)-adrenoceptor desensitization
      induced by noradrenaline was not modified by H(2)O(2), suggesting a selective
      action of ROS on MOR. Our results suggest that elevated levels of NO, which may
      be reached in pathological processes, enhance homologous desensitization of MOR
      in the LC, probably through a mechanism involving ROS generation.

PMID- 22593096
TI  - A long-time limit for world subway networks.
AB  - We study the temporal evolution of the structure of the world's largest subway
      networks in an exploratory manner. We show that, remarkably, all these networks
      converge to a shape that shares similar generic features despite their
      geographical and economic differences. This limiting shape is made of a core with
      branches radiating from it. For most of these networks, the average degree of a
      node (station) within the core has a value of order 2.5 and the proportion of k =
      2 nodes in the core is larger than 60 per cent. The number of branches scales
      roughly as the square root of the number of stations, the current proportion of
      branches represents about half of the total number of stations, and the average
      diameter of branches is about twice the average radial extension of the core.
      Spatial measures such as the number of stations at a given distance to the
      barycentre display a first regime which grows as r(2) followed by another regime
      with different exponents, and eventually saturates. These results--difficult to
      interpret in the framework of fractal geometry--confirm and yield a natural
      explanation in the geometric picture of this core and their branches: the first
      regime corresponds to a uniform core, while the second regime is controlled by
      the interstation spacing on branches. The apparent convergence towards a unique
      network shape in the temporal limit suggests the existence of dominant, universal
      mechanisms governing the evolution of these structures.

PMID- 22593095
TI  - beta-adrenergic receptor mediation of stress-induced reinstatement of
      extinguished cocaine-induced conditioned place preference in mice: roles for
      beta1 and beta2 adrenergic receptors.
AB  - Stress can trigger the relapse of drug use in recovering cocaine addicts and
      reinstatement in rodent models through mechanisms that may involve norepinephrine
      release and beta-adrenergic receptor activation. The present study examined the
      role of beta-adrenergic receptor subtypes in the stressor-induced reinstatement
      of extinguished cocaine-induced (15 mg/kg i.p.) conditioned place preference in
      mice. Forced swim (6 min at 22 degrees C) stress or activation of central
      noradrenergic neurotransmission by administration of the selective alpha(2)
      adrenergic receptor antagonist 2-[(4,5-dihydro-1H-imidazol-2-yl)methyl]-2,3
      dihydro-1-methyl-1H-isoindole (BRL-44,408) (10 mg/kg i.p.) induced reinstatement
      in wild-type, but not beta- adrenergic receptor-deficient Adrb1/Adrb2 double
      knockout, mice. In contrast, cocaine administration (15 mg/kg i.p.) resulted in
      reinstatement in both wild-type and beta-adrenergic receptor knockout mice.
      Stress-induced reinstatement probably involved beta(2) adrenergic receptors. The
      beta(2) adrenergic receptor antagonist -(isopropylamino)-1-[(7-methyl-4
      indanyl)oxy]butan-2-ol (ICI-118,551) (1 or 2 mg/kg i.p.) blocked reinstatement by
      forced swim or BRL-44,408, whereas administration of the nonselective beta
      adrenergic receptor agonist isoproterenol (2 or 4 mg/kg i.p.) or the beta(2)
      adrenergic receptor-selective agonist clenbuterol (2 or 4 mg/kg i.p.) induced
      reinstatement. Forced swim-induced, but not BRL-44,408-induced, reinstatement was
      also blocked by a high (20 mg/kg) but not low (10 mg/kg) dose of the beta(1)
      adrenergic receptor antagonist betaxolol, and isoproterenol-induced reinstatement
      was blocked by pretreatment with either ICI-118,551 or betaxolol, suggesting a
      potential cooperative role for beta(1) and beta(2) adrenergic receptors in stress
      induced reinstatement. Overall, these findings suggest that targeting beta
      adrenergic receptors may represent a promising pharmacotherapeutic strategy for
      preventing drug relapse, particularly in cocaine addicts whose drug use is stress
      related.

PMID- 22593097
TI  - Elytra boost lift, but reduce aerodynamic efficiency in flying beetles.
AB  - Flying insects typically possess two pairs of wings. In beetles, the front pair
      has evolved into short, hardened structures, the elytra, which protect the second
      pair of wings and the abdomen. This allows beetles to exploit habitats that would
      otherwise cause damage to the wings and body. Many beetles fly with the elytra
      extended, suggesting that they influence aerodynamic performance, but little is
      known about their role in flight. Using quantitative measurements of the beetle's
      wake, we show that the presence of the elytra increases vertical force production
      by approximately 40 per cent, indicating that they contribute to weight support.
      The wing-elytra combination creates a complex wake compared with previously
      studied animal wakes. At mid-downstroke, multiple vortices are visible behind
      each wing. These include a wingtip and an elytron vortex with the same sense of
      rotation, a body vortex and an additional vortex of the opposite sense of
      rotation. This latter vortex reflects a negative interaction between the wing and
      the elytron, resulting in a single wing span efficiency of approximately 0.77 at
      mid downstroke. This is lower than that found in birds and bats, suggesting that
      the extra weight support of the elytra comes at the price of reduced efficiency.

PMID- 22593098
TI  - Hyaluronan hydration generates three-dimensional meso-scale structure in
      engineered collagen tissues.
AB  - Here, we show that the local incorporation of osmotically active hyaluronan into
      previously compressed collagen constructs results in further rapid
      dehydration/compression of collagen layers, channel formation and generation of
      new interfaces; these novel structures, at the nano-micro (i.e. meso-scale) were
      formed within native collagen gels, in a highly predictable spatial manner and
      offer important new methods of fabricating scaffolds (e.g. tubes and open
      spirals) with potential for use in tissue regeneration such as in peripheral
      nerves and small vessels. This paper tests the possibility that the local fluid
      content of a dense collagen network can be controlled by incorporation of an
      osmotically active (native) macromolecule--hyluronan. This is an exemplar
      physiological, osmotic swelling agent. Hyaluronan is commonly secreted by cells
      deep in connective tissues, so is a good candidate for this role in a cell-driven
      system balancing mechanical compaction of bulk tissue collagen. These constructs
      may have potential as functional in vitro models representing developmental and
      pathological processes.

PMID- 22593100
TI  - Quantifying limits to detection of early warning for critical transitions.
AB  - Catastrophic regime shifts in complex natural systems may be averted through
      advanced detection. Recent work has provided a proof-of-principle that many
      systems approaching a catastrophic transition may be identified through the lens
      of early warning indicators such as rising variance or increased return times.
      Despite widespread appreciation of the difficulties and uncertainty involved in
      such forecasts, proposed methods hardly ever characterize their expected error
      rates. Without the benefits of replicates, controls or hindsight, applications of
      these approaches must quantify how reliable different indicators are in avoiding
      false alarms, and how sensitive they are to missing subtle warning signs. We
      propose a model-based approach to quantify this trade-off between reliability and
      sensitivity and allow comparisons between different indicators. We show these
      error rates can be quite severe for common indicators even under favourable
      assumptions, and also illustrate how a model-based indicator can improve this
      performance. We demonstrate how the performance of an early warning indicator
      varies in different datasets, and suggest that uncertainty quantification become
      a more central part of early warning predictions.

PMID- 22593099
TI  - Nitric oxide transport in an axisymmetric stenosis.
AB  - To test the hypothesis that disturbed flow can impede the transport of nitric
      oxide (NO) in the artery and hence induce atherogenesis, we used a lumen-wall
      model of an idealized arterial stenosis with NO produced at the blood vessel-wall
      interface to study the transport of NO in the stenosis. Blood flows in the lumen
      and through the arterial wall were simulated by Navier-Stokes equations and
      Darcy's Law, respectively. Meanwhile, the transport of NO in the lumen and the
      transport of NO within the arterial wall were modelled by advection-diffusion
      reaction equations. Coupling of fluid dynamics at the endothelium was achieved by
      the Kedem-Katchalsky equations. The results showed that both the hydraulic
      conductivity of the endothelium and the non-Newtonian viscous behaviour of blood
      had little effect on the distribution of NO. However, the blood flow rate,
      stenosis severity, red blood cells (RBCs), RBC-free layer and NO production rate
      at the blood vessel-wall interface could significantly affect the transport of
      NO. The theoretical study revealed that the transport of NO was significantly
      hindered in the disturbed flow region distal to the stenosis. The reduced NO
      concentration in the disturbed flow region might play an important role in the
      localized genesis and development of atherosclerosis.

PMID- 22593101
TI  - Nutrition in Clinical Practice. Editor's note.

PMID- 22593102
TI  - Hemodynamic monitoring in the intensive care unit.
AB  - Patients in the intensive care unit are often critically ill with inadequate
      tissue perfusion and oxygenation. This inadequate delivery of substrates at the
      cellular level is a common definition of shock. Hemodynamic monitoring is the
      observation of cardiovascular physiology. The purpose of hemodynamic monitoring
      is to identify abnormal physiology and intervene before complications, including
      organ failure and death, occur. The most common types of invasive hemodynamic
      monitors are central venous catheters, pulmonary artery catheters, and arterial
      pulse-wave analysis. Ultrasonography is a noninvasive alternative being used in
      intensive care units for hemodynamic measurements and assessments.

PMID- 22593103
TI  - Wildlife disease elimination and density dependence.
AB  - Disease control by managers is a crucial response to emerging wildlife epidemics,
      yet the means of control may be limited by the method of disease transmission. In
      particular, it is widely held that population reduction, while effective for
      controlling diseases that are subject to density-dependent (DD) transmission, is
      ineffective for controlling diseases that are subject to frequency-dependent (FD)
      transmission. We investigate control for horizontally transmitted diseases with
      FD transmission where the control is via culling or harvest that is non-selective
      with respect to infection and the population can compensate through DD
      recruitment or survival. Using a mathematical model, we show that culling or
      harvesting can eradicate the disease, even when transmission dynamics are FD.
      Eradication can be achieved under FD transmission when DD birth or recruitment
      induces compensatory growth of new, healthy individuals, which has the net effect
      of reducing disease prevalence by dilution. We also show that if harvest is used
      simultaneously with vaccination, and there is high enough transmission
      coefficient, application of both controls may be less efficient than vaccination
      alone. We illustrate the effects of these control approaches on disease
      prevalence for chronic wasting disease in deer where the disease is transmitted
      directly among deer and through the environment.

PMID- 22593104
TI  - Chronic contamination decreases disease spread: a Daphnia-fungus-copper case
      study.
AB  - Chemical contamination and disease outbreaks have increased in many ecosystems.
      However, connecting pollution to disease spread remains difficult, in part,
      because contaminants can simultaneously exert direct and multi-generational
      effects on several host and parasite traits. To address these challenges, we
      parametrized a model using a zooplankton-fungus-copper system. In individual
      level assays, we considered three sublethal contamination scenarios: no
      contamination, single-generation contamination (hosts and parasites exposed only
      during the assays) and multi-generational contamination (hosts and parasites
      exposed for several generations prior to and during the assays). Contamination
      boosted transmission by increasing contact of hosts with parasites. However, it
      diminished parasite reproduction by reducing the size and lifespan of infected
      hosts. Multi-generational contamination further reduced parasite reproduction.
      The parametrized model predicted that a single generation of contamination would
      enhance disease spread (via enhanced transmission), whereas multi-generational
      contamination would inhibit epidemics relative to unpolluted conditions (through
      greatly depressed parasite reproduction). In a population-level experiment, multi
      generational contamination reduced the size of experimental epidemics but did not
      affect Daphnia populations without disease. This result highlights the importance
      of multi-generational effects for disease dynamics. Such integration of models
      with experiments can provide predictive power for disease problems in
      contaminated environments.

PMID- 22593105
TI  - Sons learn songs from their social fathers in a cooperatively breeding bird.
AB  - Song learning is hypothesized to allow social adaptation to a local song
      neighbourhood. Maintaining social associations is particularly important in
      cooperative breeders, yet vocal learning in such species has only been assessed
      in systems where social association was correlated with relatedness. Thus,
      benefits of vocal learning as a means of maintaining social associations could
      not be disentangled from benefits of kin recognition. We assessed genetic and
      cultural contributions to song in a species where social association was not
      strongly correlated with kinship: the cooperatively breeding, reproductively
      promiscuous splendid fairy-wren (Malurus splendens). We found that song
      characters of socially associated father-son pairs were more strongly correlated
      (and thus songs were more similar) than songs of father-son pairs with a genetic,
      but no social, association (i.e. cuckolding fathers). Song transmission was,
      therefore, vertical and cultural, with minimal signatures of kinship.
      Additionally, song characters were not correlated with several phenotypic
      indicators of male quality, supporting the idea that there may be a tradeoff
      between accurate copying of tutors and quality signalling via maximizing song
      performance, particularly when social and genetic relationships are decoupled.
      Our results lend support to the hypothesis that song learning facilitates the
      maintenance of social associations by permitting unrelated individuals to acquire
      similar signal phenotypes.

PMID- 22593106
TI  - New insights into the evolutionary rate of HIV-1 at the within-host and
      epidemiological levels.
AB  - Over calendar time, HIV-1 evolves considerably faster within individuals than it
      does at the epidemic level. This is a surprising observation since, from basic
      population genetic theory, we would expect the genetic substitution rate to be
      similar across different levels of biological organization. Three different
      mechanisms could potentially cause the observed mismatch in phylogenetic rates of
      divergence: temporal changes in selection pressure during the course of
      infection; frequent reversion of adaptive mutations after transmission; and the
      storage of the virus in the body followed by the preferential transmission of
      stored ancestral virus. We evaluate each of these mechanisms to determine whether
      they are likely to make a major contribution to the mismatch in phylogenetic
      rates. We conclude that the cycling of the virus through very long-lived memory
      CD4(+) T cells, a process that we call 'store and retrieve', is probably the
      major contributing factor to the rate mismatch. The preferential transmission of
      ancestral virus needs to be integrated into evolutionary models if we are to
      accurately predict the evolution of immune escape, drug resistance and virulence
      in HIV-1 at the population level. Moreover, early infection viruses should be the
      major target for vaccine design, because these are the viral strains primarily
      involved in transmission.

PMID- 22593107
TI  - Complex effects of temperature on mosquito immune function.
AB  - Over the last 20 years, ecological immunology has provided much insight into how
      environmental factors shape host immunity and host-parasite interactions.
      Currently, the application of this thinking to the study of mosquito immunology
      has been limited. Mechanistic investigations are nearly always conducted under
      one set of conditions, yet vectors and parasites associate in a variable world.
      We highlight how environmental temperature shapes cellular and humoral immune
      responses (melanization, phagocytosis and transcription of immune genes) in the
      malaria vector, Anopheles stephensi. Nitric oxide synthase expression peaked at
      30 degrees C, cecropin expression showed no main effect of temperature and
      humoral melanization, and phagocytosis and defensin expression peaked around 18
      degrees C. Further, immune responses did not simply scale with temperature, but
      showed complex interactions between temperature, time and nature of immune
      challenge. Thus, immune patterns observed under one set of conditions provide
      little basis for predicting patterns under even marginally different conditions.
      These quantitative and qualitative effects of temperature have largely been
      overlooked in vector biology but have significant implications for extrapolating
      natural/transgenic resistance mechanisms from laboratory to field and for the
      efficacy of various vector control tools.

PMID- 22593108
TI  - Cross-modal individual recognition in domestic horses (Equus caballus) extends to
      familiar humans.
AB  - It has recently been shown that some non-human animals can cross-modally
      recognize members of their own taxon. What is unclear is just how plastic this
      recognition system can be. In this study, we investigate whether an animal, the
      domestic horse, is capable of spontaneous cross-modal recognition of individuals
      from a morphologically very different species. We also provide the first insights
      into how cross-modal identity information is processed by examining whether there
      are hemispheric biases in this important social skill. In our preferential
      looking paradigm, subjects were presented with two people and playbacks of their
      voices to determine whether they were able to match the voice with the person.
      When presented with familiar handlers subjects could match the specific familiar
      person with the correct familiar voice. Horses were significantly better at
      performing the matching task when the congruent person was standing on their
      right, indicating marked hemispheric specialization (left hemisphere bias) in
      this ability. These results are the first to demonstrate that cross-modal
      recognition in animals can extend to individuals from phylogenetically very
      distant species. They also indicate that processes governed by the left
      hemisphere are central to the cross-modal matching of visual and auditory
      information from familiar individuals in a naturalistic setting.

PMID- 22593109
TI  - Disentangling the influence of parasite genotype, host genotype and maternal
      environment on different stages of bacterial infection in Daphnia magna.
AB  - Individuals naturally vary in the severity of infectious disease when exposed to
      a parasite. Dissecting this variation into genetic and environmental components
      can reveal whether or not this variation depends on the host genotype, parasite
      genotype or a range of environmental conditions. Complicating this task, however,
      is that the symptoms of disease result from the combined effect of a series of
      events, from the initial encounter between a host and parasite, through to the
      activation of the host immune system and the exploitation of host resources.
      Here, we use the crustacean Daphnia magna and its parasite Pasteuria ramosa to
      show how disentangling genetic and environmental factors at different stages of
      infection improves our understanding of the processes shaping infectious disease.
      Using compatible host-parasite combinations, we experimentally exclude variation
      in the ability of a parasite to penetrate the host, from measures of parasite
      clearance, the reduction in host fecundity and the proliferation of the parasite.
      We show how parasite resistance consists of two components that vary in
      environmental sensitivity, how the maternal environment influences all measured
      aspects of the within-host infection process and how host-parasite interactions
      following the penetration of the parasite into the host have a distinct temporal
      component.

PMID- 22593110
TI  - The extended evolutionary synthesis and the role of soft inheritance in
      evolution.
AB  - In recent years, a number of researchers have advocated extending the modern
      synthesis in evolutionary biology. One of the core arguments made in favour of an
      extension comes from work on soft inheritance systems, including
      transgenerational epigenetic effects, cultural transmission and niche
      construction. In this study, we outline this claim and then take issue with it.
      We argue that the focus on soft inheritance has led to a conflation of proximate
      and ultimate causation, which has in turn obscured key questions about biological
      organization and calibration across the life span to maximize average lifetime
      inclusive fitness. We illustrate this by presenting hypotheses that we believe
      incorporate the core phenomena of soft inheritance and will aid in understanding
      them.

PMID- 22593111
TI  - Seeing orange: prawns tap into a pre-existing sensory bias of the Trinidadian
      guppy.
AB  - Sensory bias, a predisposition towards certain signals, has been implicated in
      the origin of mate preferences in some species. A risk associated with these
      biases is that they can be co-opted by predators as sensory lures. Here we
      propose that the orange spots on the brown pincers of a diurnal, predatory
      species of prawn function as lures for Trinidadian guppies, which have a sensory
      bias for orange. We exposed female guppies to (i) a life-like model of this
      Trinidadian prawn with orange, green or no spots on the pincers or (ii) a live,
      novel (non-Trinidadian) crustacean (crayfish), also with spotted pincers. First,
      we provide evidence that guppies sympatric with the prawn recognized our model as
      a potential predator. Next, we found that guppies spent more time in the
      dangerous head region of the model prawn with orange-spotted pincers compared
      with unspotted pincers. Finally, we show that allopatric, but not sympatric,
      guppies spent more time in the vicinity of the head of a live crayfish when
      orange spots were added to its pincers than when brown spots were added. Our
      results suggest that the orange spots on prawn pincers can act as a sensory lure.

PMID- 22593112
TI  - Testing the independent species' arrangement assertion made by theories of
      stochastic geometry of biodiversity.
AB  - The assertion that the spatial location of different species is independent of
      each other is fundamental in major ecological theories such as neutral theory
      that describes a stochastic geometry of biodiversity. However, this assertion has
      rarely been tested. Here we use techniques of spatial point pattern analysis to
      conduct a comprehensive test of the independence assertion by analysing data from
      three large forest plots with different species richness: a species-rich tropical
      forest at Barro Colorado Island (Panama), a tropical forest in Sinharaja (Sri
      Lanka), and a temperate forest in Changbaishan (China). We hypothesize that
      stochastic dilution effects owing to increasing species richness overpower
      signals of species associations, thereby yielding approximate species
      independence. Indeed, the proportion of species pairs showing: (i) no significant
      interspecific association increased with species richness, (ii) segregation
      decreased with species richness, and (iii) small-scale interspecific interaction
      decreased with species richness. This suggests that independence may indeed be a
      good approximation in the limit of very species-rich communities. Our findings
      are a step towards a better understanding of factors governing species-rich
      communities and we propose a hypothesis to explain why species placement in
      species-rich communities approximates independence.

PMID- 22593114
TI  - Controlled study of 50-Hz repetitive transcranial magnetic stimulation for the
      treatment of Parkinson disease.
AB  - OBJECTIVE: To investigate the safety and efficacy of 50-Hz repetitive
      transcranial magnetic stimulation (rTMS) in the treatment of motor symptoms in
      Parkinson disease (PD). BACKGROUND: Progression of PD is characterized by the
      emergence of motor deficits that gradually respond less to dopaminergic therapy.
      rTMS has shown promising results in improving gait, a major cause of disability,
      and may provide a therapeutic alternative. Prior controlled studies suggest that
      an increase in stimulation frequency might enhance therapeutic efficacy. METHODS:
      In this randomized, double blind, sham-controlled study, the authors investigated
      the safety and efficacy of 50-Hz rTMS of the motor cortices in 8 sessions over 2
      weeks. Assessment of safety and clinical efficacy over a 1-month period included
      timed tests of gait and bradykinesia, Unified Parkinson's Disease Rating Scale
      (UPDRS), and additional clinical, neurophysiological, and neuropsychological
      parameters. In addition, the safety of 50-Hz rTMS was tested with
      electromyography-electroencephalogram (EMG-EEG) monitoring during and after
      stimulation. RESULTS: The authors investigated 26 patients with mild to moderate
      PD: 13 received 50-Hz rTMS and 13 sham stimulation. The 50-Hz rTMS did not
      improve gait, bradykinesia, and global and motor UPDRS, but there appeared a
      short-lived "on"-state improvement in activities of daily living (UPDRS II). The
      50-Hz rTMS lengthened the cortical silent period, but other neurophysiological
      and neuropsychological measures remained unchanged. EMG/EEG recorded no
      pathological increase of cortical excitability or epileptic activity. There were
      no adverse effects. CONCLUSION: It appears that 50-Hz rTMS of the motor cortices
      is safe, but it fails to improve motor performance and functional status in PD.
      Prolonged stimulation or other techniques with rTMS might be more efficacious but
      need to be established in future research.

PMID- 22593113
TI  - Herpes simplex virus vector-mediated expression of interleukin-10 reduces below
      level central neuropathic pain after spinal cord injury.
AB  - BACKGROUND: Neuroimmune activation in the spinal dorsal horn plays an important
      role in the pathogenesis of chronic pain after peripheral nerve injury.
      OBJECTIVE: The aim of this study was to examine the role of neuroimmune
      activation in below-level neuropathic pain after traumatic spinal cord injury
      (SCI). METHODS: Right hemilateral SCI was created in male Sprague-Dawley rats by
      controlled blunt impact through a T12 laminectomy. Pain-related behaviors were
      assessed using both evoked reflex responses and an operant conflict-avoidance
      test. Neuroimmune activation was blocked by the anti-inflammatory cytokine
      interleukin-10 (IL-10) delivered by a nonreplicating herpes simplex virus (HSV)
      based gene transfer vector (vIL10). Markers of neuroimmune activation were
      assessed using immunohistochemistry and Western blot. RESULTS: One week after
      SCI, injured animals demonstrated mechanical allodynia, thermal hyperalgesia, and
      mechanical hyperalgesia in the hind limbs below the level of injury. Animals
      inoculated with vIL10 had a statistically significant reduction in all of these
      measures compared to injured rats or injured rats inoculated with control vector.
      Conflict-avoidance behavior of injured rats inoculated with vIL10 was consistent
      with significantly reduced pain compared with injured rats injected with control
      vector. These behavioral results correlated with a significant decrease in spinal
      tumor necrosis factor alpha (mTNFalpha) expression assessed by Western blot and
      astrocyte activation assessed by glial fibrillary acidic protein
      immunohistochemistry. CONCLUSION: Below-level pain after SCI is characterized by
      neuroimmune activation (increase mTNFalpha and astrocyte activation). Blunting of
      the neuroimmune response by HSV-mediated delivery of IL-10 reduced pain-related
      behaviors, and may represent a potential novel therapeutic agent.

PMID- 22593115
TI  - The diagnostic accuracy of static posturography in predicting accidental falls in
      people with multiple sclerosis.
AB  - BACKGROUND: Quantitative posturography has been reported as a reliable tool to
      measure balance in people with multiple sclerosis (MS). However, data on its
      diagnostic accuracy in predicting the occurrence of falls are lacking. OBJECTIVE:
      To determine sensitivity, specificity, predictive values, and accuracy of
      posturography in detecting falls in MS subjects over a 3-month follow-up period.
      METHODS: . One hundred consecutive patients with MS were tested by the Berg
      Balance Scale (BBS) and by static posturography on a monoaxial platform.
      Participants recorded the occurrence of accidental falls for the next 3 months.
      Abnormal cutoff values for static standing balance measures were set at 2
      standard deviations above the mean values obtained from 50 healthy controls (HC).
      The diagnostic accuracy of the BBS and static posturography was analyzed with
      respect to the prospectively collected data on the occurrence of falls. RESULTS:
      Posturometric measures in participants with MS were significantly worse than in
      HC (all P values <.0001); however, only the center of pressure (COP) path with
      open eyes condition had substantial test-retest reliability. Static posturography
      was more sensitive (88% vs 37%) and accurate (75% vs 63%), but slightly less
      specific (67% vs 81%), than the BBS in predicting accidental falls. A logistic
      regression analysis revealed that the worse the COP path, the greater the risk
      for accidental falls (odds ratio = 1.08; P < .0001), even after adjusting for
      sex, age, disease duration, body mass index, MS subtype, Expanded Disability
      Status Scale, and BBS score. CONCLUSION: The COP path measurement in static
      position is a sensitive and accurate tool to identify people with MS who are at
      risk of accidental falls.

PMID- 22593116
TI  - Telling the right hand from the left hand: multisensory integration, not motor
      imagery, solves the problem.
AB  - Judging the laterality of a hand seen at unanticipated orientations evokes a
      robust feeling of bodily movement, even though no movement is produced. In two
      experiments, we tested a novel hypothesis to explain this phenomenon: A hand's
      laterality is determined via a multisensory binding of the visual representation
      of the seen hand and a proprioceptive representation of the observer's felt hand,
      and the felt "movement" is an obligatory aftereffect of intersensory
      recalibration. Consistent with the predictions implied by such a cross-modal
      mechanism, our results in Experiment 1 showed that manipulating observers'
      selective attention can evoke illusory feelings of movement in the "wrong" hand
      (i.e., the hand whose laterality does not match that of the stimulus). In
      Experiment 2, these illusions were readily extinguished in conditions in which
      binding was predicted to fail, a result indicating that cross-modal binding was
      necessary to produce them. These results are not explained by imagery, a
      mechanism widely assumed to account for how hand laterality is identified.

PMID- 22593117
TI  - The path to glory is paved with hierarchy: when hierarchical differentiation
      increases group effectiveness.
AB  - Two experiments examined the psychological and biological antecedents of
      hierarchical differentiation and the resulting consequences for productivity and
      conflict within small groups. In Experiment 1, which used a priming manipulation,
      hierarchically differentiated groups (i.e., groups comprising 1 high-power
      primed, 1 low-power-primed, and 1 baseline individual) performed better on a
      procedurally interdependent task than did groups comprising exclusively either
      all high-power-primed or all low-power-primed individuals. There were no effects
      of hierarchical differentiation on performance on a procedurally independent
      task. Experiment 2 used a biological marker of dominance motivation (prenatal
      testosterone exposure as measured by a digit-length ratio) to manipulate
      hierarchical differentiation. The pattern of results from Experiment 1 was
      replicated; mixed-testosterone groups achieved greater productivity than did
      groups comprising all high-testosterone or all low-testosterone individuals.
      Furthermore, intragroup conflict mediated the productivity decrements for the
      high-testosterone but not the low-testosterone groups. This research suggests
      possible directions for future research and the need to further delineate the
      conditions and types of hierarchy under which hierarchical differentiation
      enhances rather than undermines group effectiveness.

PMID- 22593118
TI  - Semantic priming from crowded words.
AB  - Vision in a cluttered scene is extremely inefficient. This damaging effect of
      clutter, known as crowding, affects many aspects of visual processing (e.g.,
      reading speed). We examined observers' processing of crowded targets in a lexical
      decision task, using single-character Chinese words that are compact but carry
      semantic meaning. Despite being unrecognizable and indistinguishable from matched
      nonwords, crowded prime words still generated robust semantic-priming effects on
      lexical decisions for test words presented in isolation. Indeed, the semantic
      priming effect of crowded primes was similar to that of uncrowded primes. These
      findings show that the meanings of words survive crowding even when the
      identities of the words do not, suggesting that crowding does not prevent
      semantic activation, a process that may have evolved in the context of a
      cluttered visual environment.

PMID- 22593119
TI  - The social dimension of stress reactivity: acute stress increases prosocial
      behavior in humans.
AB  - Psychosocial stress precipitates a wide spectrum of diseases with major public
      health significance. The fight-or-flight response is generally regarded as the
      prototypic human stress response, both physiologically and behaviorally. Given
      that having positive social interactions before being exposed to acute stress
      plays a preeminent role in helping individuals control their stress response,
      engaging in prosocial behavior in response to stress (tend-and-befriend) might
      also be a protective pattern. Little is known, however, about the immediate
      social responses following stress in humans. Here we show that participants who
      experienced acute social stress, induced by a standardized laboratory stressor,
      engaged in substantially more prosocial behavior (trust, trustworthiness, and
      sharing) compared with participants in a control condition, who did not
      experience socioevaluative threat. These effects were highly specific: Stress did
      not affect the readiness to exhibit antisocial behavior or to bear nonsocial
      risks. These results show that stress triggers social approach behavior, which
      operates as a potent stress-buffering strategy in humans, thereby providing
      evidence for the tend-and-befriend hypothesis.

PMID- 22593121
TI  - Feasibility of epicardial adipose tissue quantification in non-ECG-gated low
      radiation-dose CT: comparison with prospectively ECG-gated cardiac CT.
AB  - BACKGROUND: Epicardial adipose tissue (EAT) is an important indicator of
      cardiovascular risk. This parameter is generally assessed on ECG-gated computed
      tomography (CT) images. PURPOSE: To evaluate feasibility and reliability of EAT
      quantification on non-gated thoracic low-radiation-dose CT examinations with
      respect to prospectively ECG-gated cardiac CT acquisition. MATERIAL AND METHODS:
      Sixty consecutive asymptomatic smokers (47 men; mean age 64 +/- 9.8 years)
      underwent low-dose CT of the chest and prospectively ECG-gated cardiac CT
      acquisitions (64-slice dual-source CT). The two examinations were reconstructed
      with the same range, field of view, slice thickness, and convolution algorithm.
      Two independent observers blindly quantified EAT volume using commercially
      available software. Data were compared with paired sample Student t-test,
      concordance correlation coefficients (CCC), and Bland-Altman plots. RESULTS: No
      statistically significant difference was observed for EAT volume quantification
      with low-dose-CT (141.7 +/- 58.3 mL) with respect to ECG-gated CT (142.7 +/- 57.9
      mL). Estimation of CCC showed almost perfect concordance between the two
      techniques for EAT-volume assessment (CCC, 0.99; mean difference, 0.98 +/- 5.1
      mL). Inter-observer agreement for EAT volume estimation was CCC: 0.96 for low
      dose-CT examinations and 0.95 for ECG-gated CT. CONCLUSION: Non-gated low-dose CT
      allows quantifying EAT with almost the same concordance and reliability as using
      dedicated prospectively ECG-gated cardiac CT acquisition protocols.

PMID- 22593120
TI  - Digital breast tomosynthesis (DBT): initial experience in a clinical setting.
AB  - BACKGROUND: Digital breast tomosynthesis (DBT) is a promising new technology.
      Some experimental clinical studies have shown positive results, but the future
      role and indications of this new technique, whether in a screening or clinical
      setting, need to be evaluated. PURPOSE: To compare digital mammography and DBT in
      a side-by-side feature analysis for cancer conspicuity, and to assess whether
      there is a potential additional value of DBT to standard state-of-the-art
      conventional imaging work-up with respect to detection of additional
      malignancies. MATERIAL AND METHODS: The study had ethics committee approval. A
      total of 129 women underwent 2D digital mammography including supplementary cone
      down and magnification views and breast ultrasonography if indicated, as well as
      digital breast tomosynthesis. The indication for conventional imaging in the
      clinical setting included a palpable lump in 30 (23%), abnormal mammographic
      screening findings in 54 (42%), and surveillance in 45 (35%) of the women. The
      women were examined according to present guidelines, including spot-magnification
      views, ultrasonography, and needle biopsies, if indicated. The DBT examinations
      were interpreted several weeks after the conventional imaging without knowledge
      of the conventional imaging findings. In a later session, three radiologists
      performed a side-by-side feature analysis for cancer conspicuity in a sample of
      50 cases. RESULTS: State-of-the-art conventional imaging resulted in needle
      biopsy of 45 breasts, of which 20 lesions were benign and a total of 25 cancers
      were diagnosed. The remaining 84 women were dismissed with a normal/definitely
      benign finding and without indication for needle biopsy. The subsequent DBT
      interpretation found suspicious findings in four of these 84 women, and these
      four women had to be called back for repeated work-up with knowledge of the
      tomosynthesis findings. These delayed work-ups resulted in two cancers
      (increasing the cancer detection by 8%) and two false-positive findings. The side
      by-side feature analysis showed higher conspicuity scores for tomosynthesis
      compared to conventional 2D for cancers presenting as spiculated masses and
      distortions. CONCLUSION: Tomosynthesis is a promising new technique. Our
      preliminary clinical experience shows that there is a potential for increasing
      the sensitivity using this new technique, especially for cancers manifesting as
      spiculated masses and distortions.

PMID- 22593122
TI  - Coil embolization for treatment of vascular complications after nephron-sparing
      surgery.
AB  - Nephron-sparing surgery (NSS) is a standard surgical treatment for small renal
      tumors. We report four patients (aged 35-79 years) with vascular complications
      within 6 days to 3 months after open NSS. Three patients developed acute
      symptoms, whereas one was asymptomatic. Computed tomography (CT) in the arterial
      and venous phase of contrast enhancement was performed for diagnosis, followed by
      angiography. CT demonstrated a perirenal hematoma in three and an arterial
      pseudoaneurysm in two cases. Unlike CT, digital subtraction angiography confirmed
      an arterial pseudoaneurysm in all cases and additionally found an arteriovenous
      fistula in three. In all cases, angiography-guided coil embolization successfully
      treated the vascular pathology, while preserving renal function. Clinicians
      should understand the diagnosis and management of this complication of NSS.

PMID- 22593123
TI  - Comparison between visual assessment of MTA and hippocampal volumes in an
      elderly, non-demented population.
AB  - BACKGROUND: It is important to have a replicable easy method for monitoring
      atrophy progression in Alzheimer's disease. Volumetric methods for calculating
      hippocampal volume are time-consuming and commonly used in research. Visual
      assessments of medial temporal lobe atrophy (vaMTA) is a rapid method for
      clinical use. This method has not been tested in a large non-demented population
      in comparison with volumetry measurements. Since hippocampal volume decreases
      with time even in normal aging there is also a need to study the normal age
      differences of medial temporal lobe atrophy. PURPOSE: To compare visual
      assessment of medial temporal lobe atrophy (vaMTA) with hippocampal volume in a
      healthy, non-demented elderly population. To describe normal ageing using vaMTA.
      MATERIAL AND METHODS: Non-demented individuals aged 60, 66, 72, 78, 81, 84, and
      >=87 years old were recruited from the Swedish National study on Ageing and Care
      in Kungsholmen (SNAC-K), Sweden. Standard magnetic resonance imaging (MRI) scans,
      vaMTA, and calculations of hippocampal volumes were performed in 544 subjects.
      RESULTS: Significant correlation (r(s) = -0.32, P < 0.001, sin; and r(s) = -0.26,
      P < 0.001, dx) was found between hippocampal volume measurements and vaMTA. In
      normal ageing, almost 95% of <=66-year-olds had a medial temporal lobe atrophy
      (MTA) score <=1, with possible scores ranging from 0 to 4. Subjects aged 72, 78,
      and 81 years scored <=2, while the two oldest age groups had scores <=3.
      CONCLUSION: There was a highly significant correlation between volumetric
      measurements of the hippocampus and MTA scoring. In normal ageing, there is
      increasing MTA score. For non-demented elderly individuals <=70 years, an MTA
      score of 0-1 may be considered normal, compared with MTA <=2 for 70-80-years and
      MTA 3 for >80-year-old individuals.

PMID- 22593124
TI  - Analysis of incidental focal hypermetabolic uptake in the breast as detected by
      18F-FDG PET/CT: clinical significance and differential diagnosis.
AB  - BACKGROUND: With the widespread use of PET/CT, incidental hypermetabolic foci
      unrelated to the known malignancy have been described with increasing frequency.
      PURPOSE: To determine the frequency and clinical significance of incidental focal
      hypermetabolic uptake in the breast as detected by 18F-FDG PET/CT, and to explore
      factors differentiating benign and malignant breast uptake. MATERIAL AND METHODS:
      From January 2005 to June 2010, a total of 51,971 whole-body FDG PET/CT
      examinations were performed in our clinic. After excluding 7254 sets of PET/CT
      data from patients known to have breast cancer, we retrospectively identified
      patients showing incidental focal hypermetabolic activity in the breast. Of
      44,717 PET/CT examinations conducted on 32,988 patients, we identified 131
      patients with no previous known or suspected benign and malignant breast disease.
      The etiology, mean SUV(max), and diameter of breast lesions were assessed. We
      also compared the presentation of the lesions on CT, mammography, and
      ultrasonography. RESULTS: Of the 131 patients, 60 were histologically diagnosed
      with breast lesions, including 32 with malignant and 28 with benign lesions. An
      additional 11 patients were followed-up for more than 2 years and were clinically
      considered to have benign lesions. The remaining 60 patients who had neither
      histologic confirmation nor followed-up for more than 2 years were excluded.
      Therefore, 71 patients were finally included. The mean SUV(max) of 39 benign
      lesions and 32 malignant lesions were 2.02 +/- 1.52 and 3.71 +/- 3.83,
      respectively (P = 0.0001). At a cut-off value of 2.3, the rate of malignancy and
      specificity of the mean SUVmax for differentiating benign and malignant breast
      lesions were 61.3%, 76.3, respectively. The CT data from PET/CT revealed that the
      mean diameters of benign and malignant lesions were 1.19 +/- 0.97 cm and 2.26 +/-
      1.96 cm, respectively (P = 0.0009). CONCLUSION: Incidental focal 18F-FDG uptake
      in the breast as detected by PET/CT was indicative of malignancy in 45% of
      patients. Both mean SUV(max) and diameter were greater for malignant than benign
      lesions.

PMID- 22593125
TI  - Patient blood management is a win-win: a wake-up call.

PMID- 22593126
TI  - Supplemental intravenous crystalloids for the prevention of postoperative nausea
      and vomiting: quantitative review.
AB  - Hypovolaemia after overnight fasting is believed to exacerbate postoperative
      nausea and vomiting (PONV). However, data on the efficacy of supplemental i.v.
      crystalloids for PONV prophylaxis are conflicting. We performed a literature
      search using CENTRAL, MEDLINE, EMBASE, CINAHL, and Web of Science. We included
      prospective randomized controlled trials that reported PONV event rates in
      patients receiving supplemental i.v. crystalloids or a conservative fluid regimen
      after elective surgery under general anaesthesia. Studies were evaluated with
      regard to random sequence generation, allocation concealment, blinding of
      participants, personnel, and outcome assessment, incomplete outcome data, and
      selective reporting. We identified 15 trials (n=787 crystalloids; n=783
      conservative fluids). Compared with conservative fluids, i.v. crystalloids
      reduced the risk of early postoperative nausea (PON) (relative risk 0.73, 95%
      confidence interval 0.59-0.89; P=0.003), late PON (0.41, 0.22-0.76; P=0.004), and
      overall PON (0.66, 0.46-0.95; P=0.02). I.V. crystalloids did not reduce the risk
      of early postoperative vomiting (POV) (0.66, 0.37-1.16; P=0.16) or late POV
      (0.52, 0.25-1.11; P=0.09), but did reduce overall POV (0.48, 0.29-0.79; P=0.004).
      I.V. crystalloids did not reduce the risk of early PONV (0.74, 0.49-1.12;
      P=0.16), but did reduce the risk of late PONV (0.27, 0.13-0.54; P<0.001) and
      overall PONV (0.59, 0.42-0.84; P=0.003). I.V. crystalloids reduced the need for
      antiemetic rescue treatment (0.56, 0.45-0.68; P<0.001). In summary, supplemental
      i.v. crystalloids were associated with a lower incidence of several PONV
      outcomes. However, a number of PONV outcomes failed to reach statistical
      significance, perhaps due to the lack of power. Thus, studies sufficiently
      powered for the less frequent outcomes (e.g. POV) are required.

PMID- 22593127
TI  - IgE-mediated allergy to local anaesthetics: separating fact from perception: a UK
      perspective.
AB  - Local anaesthetic (LA) agents have been routinely used in dentistry,
      ophthalmology, minor surgery, and obstetrics since the late nineteenth century.
      Reports relating to adverse reactions and LA allergy have appeared in the
      published literature for several years. However, the incidence of true, IgE
      mediated LA allergy remains uncertain and is presumed to be very low. We
      critically reviewed the English language literature on suspected LA allergy and
      its investigation with the aim of estimating the reported prevalence and
      analysing the role of different tests currently used to identify and confirm LA
      allergy. Twenty-three case series involving 2978 patients were identified and
      analysed. Twenty-nine of these patients had true IgE-mediated allergy to LA, thus
      confirming the reported prevalence of LA allergy in large series to be <1%
      (0.97%). The protocols used in the investigation of these patients have also been
      discussed. Evidence from this review confirms the rarity of IgE-mediated allergy
      to LA and supports an investigation strategy based on using the clinical history
      to select patients for skin testing and challenge. We believe that such a triage
      process would alleviate pressures on allergy services without compromising
      patient safety.

PMID- 22593128
TI  - Effect of a patient blood management programme on preoperative anaemia,
      transfusion rate, and outcome after primary hip or knee arthroplasty: a quality
      improvement cycle.
AB  - BACKGROUND: There are few data on the associations between anaemia, allogeneic
      blood transfusion (ABT), patient blood management, and outcome after arthroplasty
      in the UK. National agencies nevertheless instruct NHS Trusts to implement blood
      conservation measures including preoperative anaemia management. Internationally,
      blood management programmes show encouraging results. METHODS: We retrospectively
      audited 717 primary hip or knee arthroplasties in a UK general hospital and
      conducted regression analyses to identify outcome predictors. We used these data
      to modify previously published algorithms for UK practice and audited its
      introduction prospectively. The retrospective audit group served as a control.
      RESULTS: Preoperative haemoglobin (Hb) concentration predicted ABT (odds ratio
      0.25 per 1 g dl(-1), P<0.001). It also predicted the length of stay (LOS, effect
      size -0.7 days per 1 g dl(-1), P=0.004) independently of ABT, including in non
      anaemic patients. Patient blood management implementation was associated with
      lower ABT rates for hip (23-7%, P<0.001) and knee (7-0%, P=0.001) arthroplasty.
      LOS for total hip replacement and total knee replacement decreased from 6 (5-8)
      days to 5 (3-7) and 4 (3-6) days, respectively, after algorithm implementation
      (P<0.001). The all-cause re-admission rate within 90 days decreased from 13.5%
      (97/717) before to 8.2% (23/281) after algorithm implementation (P=0.02).
      CONCLUSIONS: We conclude that preoperative Hb predicts markers of arthroplasty
      outcome in UK practice. A systematic approach to optimize Hb mass before
      arthroplasty and limit Hb loss perioperatively was associated with improved
      outcome up to 90 days after discharge.

PMID- 22593129
TI  - Fluid physiology, tissue compliance, and colloids.

PMID- 22593131
TI  - Intraoperative goal-directed fluid therapy in aerobically fit and unfit patients
      having major colorectal surgery.

PMID- 22593132
TI  - Re: Randomized controlled trial of intraoperative goal-directed fluid therapy in
      aerobically fit and unfit patients having major colorectal surgery.

PMID- 22593134
TI  - Postoperative sore throat: a multifactorial problem.

PMID- 22593136
TI  - Use of the Aintree intubation and airway exchange catheters through LMA-ProSeal
      for double-lumen tube placement in a morbidly obese patient with right main stem
      bronchus tumour.

PMID- 22593137
TI  - Effects of oxytocin on Purkinje fibres.

PMID- 22593138
TI  - Utility of lung ultrasound.

PMID- 22593139
TI  - Ultrasound-guided nerve blocks in the Charcot-Marie-Tooth disease and
      Friedreich's ataxia.

PMID- 22593140
TI  - Acute Budd-Chiari syndrome during veno-venous extracorporeal membrane oxygenation
      diagnosed using transthoracic echocardiography.

PMID- 22593146
TI  - The clinical and molecular relations between idiopathic preterm labor and
      maternal congenital heart defects.
AB  - Preterm labor (PTL) is an important cause of preterm delivery. The trigger
      initiating the process toward overt labor and parturition is poorly understood
      and the molecular basis remains an enigma. It recently emerged that the overall
      occurrence of PTL in pregnant women with congenital heart disease (CHD) is
      increased. In this review, we present data on pregnancy in women with CHD and the
      opportunities this provides for research on the initiating mechanisms of
      inappropriately premature contractions. This may provide means for early
      detection of women at high risk of PTL in the general population, with models
      using cervical length, novel biomarkers, and maternal factors. We discuss human
      embryonic development of the heart and the uterus and the molecular pathways
      shared by the cardio- and uteromyocytes. We propose 2 hypotheses for the co
      occurrence of maternal CHD and PTL; one based on a shared genetic origin and the
      other on a shared epigenetic origin.

PMID- 22593147
TI  - Organochlorine pollutants and female fertility: a systematic review focusing on
      in vitro fertilization studies.
AB  - The possible adverse effects of organochlorine pollutants (OPs) on human
      fertility are a matter of concern. Direct evaluation of the effects on female
      fertility was made possible by the advent of in vitro fertilization (IVF). We
      conducted a systematic review to assess possible associations between OP levels
      and selected indicators of female fertility in the context of IVF. After
      harmonization, OP concentrations per unit of lipid varied considerably, OP
      concentrations were higher in follicular than in serum and conflicting results
      were obtained. No significant adverse association between OP concentration and
      female fertility was observed in some studies. In other reports, there were
      indications of various degrees of significance that oocyte, embryo quality, and
      implantation may have been impaired. Thus, this review provides no evidence to
      support the hypothesis that OPs impair female fertility but insufficient evidence
      to reject this hypothesis. Our conclusions are limited by the diversity of the
      protocols used, OPs studied, and the quality of the studies selected. The IVF
      provides a unique context in which to assess the impact of OPs on female
      fertility, but it is subject to several limitations. Potential frameworks for
      future studies are proposed.

PMID- 22593148
TI  - Predicting relapse for Catholic clergy sex offenders: the use of the static-99.
AB  - The Static-99 is an instrument commonly used to measure the likelihood of
      recidivism among sex offenders. The current study explores whether the Static-99
      is an effective predictor of relapse among Catholic clergy who have had sexual
      contact with minors. Static-99 scores were compiled for 337 treated clergy who
      had offended against minors, including 21 who were known to have relapsed after
      treatment. Clergy were followed up for 5 to 25 years posttreatment (M = 16.05; SD
      = 5.12) after their completion of treatment. Post release, they were closely
      supervised, with explicit rules limiting their contacts with minors and church
      officials monitoring their compliance with posttreatment plans. Descriptive
      information on the victims of clergy sex offenders is provided. Although all
      clergy offenders had the same score on 4 of the 10 Static-99 items, Static-99
      total scores still significantly predicted relapse with a moderate to large
      effect size (area under the curve [AUC] = .672; Cohen's d = .808). Predictive
      accuracy of each item is also reported. Issues concerning the use of the Static
      99 with this population are discussed.

PMID- 22593149
TI  - Poly(A)-binding protein facilitates translation of an uncapped/nonpolyadenylated
      viral RNA by binding to the 3' untranslated region.
AB  - Viruses employ an alternative translation mechanism to exploit cellular resources
      at the expense of host mRNAs and to allow preferential translation. Plant RNA
      viruses often lack both a 5' cap and a 3' poly(A) tail in their genomic RNAs.
      Instead, cap-independent translation enhancer elements (CITEs) located in the 3'
      untranslated region (UTR) mediate their translation. Although eukaryotic
      translation initiation factors (eIFs) or ribosomes have been shown to bind to the
      3'CITEs, our knowledge is still limited for the mechanism, especially for
      cellular factors. Here, we searched for cellular factors that stimulate the
      3'CITE-mediated translation of Red clover necrotic mosaic virus (RCNMV) RNA1
      using RNA aptamer-based one-step affinity chromatography, followed by mass
      spectrometry analysis. We identified the poly(A)-binding protein (PABP) as one of
      the key players in the 3'CITE-mediated translation of RCNMV RNA1. We found that
      PABP binds to an A-rich sequence (ARS) in the viral 3' UTR. The ARS is conserved
      among dianthoviruses. Mutagenesis and a tethering assay revealed that the PABP
      ARS interaction stimulates 3'CITE-mediated translation of RCNMV RNA1. We also
      found that both the ARS and 3'CITE are important for the recruitment of the plant
      eIF4F and eIFiso4F factors to the 3' UTR and of the 40S ribosomal subunit to the
      viral mRNA. Our results suggest that dianthoviruses have evolved the ARS and
      3'CITE as substitutes for the 3' poly(A) tail and the 5' cap of eukaryotic mRNAs
      for the efficient recruitment of eIFs, PABP, and ribosomes to the
      uncapped/nonpolyadenylated viral mRNA.

PMID- 22593150
TI  - Mapping a neutralizing epitope onto the capsid of adeno-associated virus serotype
      8.
AB  - Adeno-associated viruses (AAVs) are small single-stranded DNA viruses that can
      package and deliver nongenomic DNA for therapeutic gene delivery. AAV8, a liver
      tropic vector, has shown great promise for the treatment of hemophilia A and B.
      However, as with other AAV vectors, host anti-capsid immune responses are a
      deterrent to therapeutic success. To characterize the antigenic structure of this
      vector, cryo-electron microscopy and image reconstruction (cryo-reconstruction)
      combined with molecular genetics, biochemistry, and in vivo approaches were used
      to define an antigenic epitope on the AAV8 capsid surface for a neutralizing
      monoclonal antibody, ADK8. Docking of the crystal structures of AAV8 and a
      generic Fab into the cryo-reconstruction for the AAV8-ADK8 complex identified a
      footprint on the prominent protrusions that flank the 3-fold axes of the
      icosahedrally symmetric capsid. Mutagenesis and cell-binding studies, along with
      in vitro and in vivo transduction assays, showed that the major ADK8 epitope is
      formed by an AAV variable region, VRVIII (amino acids 586 to 591 [AAV8 VP1
      numbering]), which lies on the surface of the protrusions facing the 3-fold axis.
      This region plays a role in AAV2 and AAV8 cellular transduction. Coincidently,
      cell binding and trafficking assays indicate that ADK8 affects a postentry step
      required for successful virus trafficking to the nucleus, suggesting a probable
      mechanism of neutralization. This structure-directed strategy for characterizing
      the antigenic regions of AAVs can thus generate useful information to help re
      engineer vectors that escape host neutralization and are hence more efficacious.

PMID- 22593151
TI  - Single amino acid modification of adeno-associated virus capsid changes
      transduction and humoral immune profiles.
AB  - Adeno-associated virus (AAV) vectors have the potential to promote long-term gene
      expression. Unfortunately, humoral immunity restricts patient treatment and in
      addition provides an obstacle to the potential option of vector readministration.
      In this study, we describe a comprehensive characterization of the neutralizing
      antibody (NAb) response to AAV type 1 (AAV1) through AAV5 both in vitro and in
      vivo. These results demonstrated that NAbs generated from one AAV type are unable
      to neutralize the transduction of other types. We extended this observation by
      demonstrating that a rationally engineered, muscle-tropic AAV2 mutant containing
      5 amino acid substitutions from AAV1 displayed a NAb profile different from those
      of parental AAV2 and AAV1. Here we found that a single insertion of Thr from AAV1
      into AAV2 capsid at residue 265 preserved high muscle transduction, while also
      changing the immune profile. To better understand the role of Thr insertion at
      position 265, we replaced all 20 amino acids and evaluated both muscle
      transduction and the NAb response. Of these variants, 8 mutants induced higher
      muscle transduction than AAV2. Additionally, three classes of capsid NAb immune
      profile were defined based on the ability to inhibit transduction from AAV2 or
      mutants. While no relationship was found between transduction, amino acid
      properties, and NAb titer or its cross-reactivity, these studies map a critical
      capsid motif involved in all steps of AAV infectivity. Our results suggest that
      AAV types can be utilized not only as templates to generate mutants with enhanced
      transduction efficiency but also as substrates for repeat administration.

PMID- 22593152
TI  - Gene-based vaccination with a mismatched envelope protects against simian
      immunodeficiency virus infection in nonhuman primates.
AB  - The RV144 trial demonstrated that an experimental AIDS vaccine can prevent human
      immunodeficiency virus type 1 (HIV-1) infection in humans. Because of its limited
      efficacy, further understanding of the mechanisms of preventive AIDS vaccines
      remains a priority, and nonhuman primate (NHP) models of lentiviral infection
      provide an opportunity to define immunogens, vectors, and correlates of immunity.
      In this study, we show that prime-boost vaccination with a mismatched SIV
      envelope (Env) gene, derived from simian immunodeficiency virus SIVmac239,
      prevents infection by SIVsmE660 intrarectally. Analysis of different gene-based
      prime-boost immunization regimens revealed that recombinant adenovirus type 5
      (rAd5) prime followed by replication-defective lymphocytic choriomeningitis virus
      (rLCMV) boost elicited robust CD4 and CD8 T-cell and humoral immune responses.
      This vaccine protected against infection after repetitive mucosal challenge with
      efficacies of 82% per exposure and 62% cumulatively. No effect was seen on
      viremia in infected vaccinated monkeys compared to controls. Protection
      correlated with the presence of neutralizing antibodies to the challenge viruses
      tested in peripheral blood mononuclear cells. These data indicate that a vaccine
      expressing a mismatched Env gene alone can prevent SIV infection in NHPs and
      identifies an immune correlate that may guide immunogen selection and immune
      monitoring for clinical efficacy trials.

PMID- 22593153
TI  - Suppression of extracellular signal-regulated kinase activity in herpes simplex
      virus 1-infected cells by the Us3 protein kinase.
AB  - Host mitogen-activated protein kinases (MAPKs) are deregulated by herpes simplex
      virus 1 (HSV-1). Unlike p38 MAPK and Jun N-terminal protein kinase (JNK), which
      require ICP27 for their activation early in infection, extracellular signal
      regulated kinase (ERK) activity is suppressed by an unknown mechanism. Here, we
      establish that HSV-1-induced suppression of ERK activity requires viral gene
      expression, occurs with delayed-early kinetics, and requires the functional virus
      encoded Us3 Ser/Thr protein kinase. Finally, Us3 expression in uninfected cells
      was necessary and sufficient to suppress ERK activity in the absence of any other
      virus-encoded gene products. This demonstrates that inhibition of ERK activity in
      HSV-1-infected cells is an intrinsic Us3 function and defines a new role for this
      alphaherpesvirus Us3 kinase in regulating MAPK activation in infected cells.

PMID- 22593155
TI  - Enhancement or attenuation of disease by deletion of genes from Citrus tristeza
      virus.
AB  - Stem pitting is a common virus-induced disease of perennial woody plants induced
      by a range of different viruses. The phenotype results from sporadic areas of the
      stem in which normal xylem and phloem development is prevented during growth of
      stems. These alterations interfere with carbohydrate transport, resulting in
      reduced plant growth and yield. Citrus tristeza virus (CTV), a phloem-limited
      closterovirus, induces economically important stem-pitting diseases of citrus.
      CTV has three nonconserved genes (p33, p18, and p13) that are not related to
      genes of other viruses and that are not required for systemic infection of some
      species of citrus, which allowed us to examine the effect of deletions of these
      genes on symptom phenotypes. In the most susceptible experimental host, Citrus
      macrophylla, the full-length virus causes only very mild stem-pitting symptoms.
      Surprisingly, we found that certain deletion combinations (p33 and p18 and/or
      p13) induced greatly increased stem-pitting symptoms, while other combinations
      (p13 or p13 plus p18) resulted in reduced stem pitting. These results suggest
      that the stem-pitting phenotype, which is one of more economically important
      disease phenotypes, can result not from a specific sequence or protein but from a
      balance between the expression of different viral genes. Unexpectedly, using
      green fluorescent protein-tagged full-length virus and deletion mutants
      (CTV9Deltap33 and CTV9Deltap33Deltap18Deltap13), the virus was found at pitted
      areas in abnormal locations outside the normal ring of phloem. Thus, increased
      stem pitting was associated not only with a prevention of xylem production but
      also with a proliferation of cells that supported viral replication, suggesting
      that at random areas of stems the virus can elicit changes in cellular
      differentiation and development.

PMID- 22593154
TI  - Expression of human endogenous retrovirus type K (HML-2) is activated by the Tat
      protein of HIV-1.
AB  - Human endogenous retroviruses (HERVs) make up 8% of the human genome. The
      expression of HERV-K (HML-2), the family of HERVs that most recently entered the
      genome, is tightly regulated but becomes markedly increased after infection with
      HIV-1. To better understand the mechanisms involved in this activation, we
      explored the role of the HIV-1 Tat protein in inducing the expression of these
      endogenous retroviral genes. Administration of recombinant HIV-1 Tat protein
      caused a 13-fold increase in HERV-K (HML-2) gag RNA transcripts in Jurkat T cells
      and a 10-fold increase in primary lymphocytes, and the expression of the HERV-K
      (HML-2) rec and np9 oncogenes was also markedly increased. This activation was
      seen especially in lymphocytes and monocytic cells, the natural hosts for HIV-1
      infection. Luciferase reporter gene assays demonstrated that the effect of Tat on
      HERV-K (HML-2) expression occurred at the level of the transcriptional promoter.
      The transcription factors NF-kappaB and NF-AT contribute to the Tat-induced
      activation of the promoter, as shown by chromatin immunoprecipitation assays,
      mutational analysis of the HERV-K (HML-2) long terminal repeat, and treatments
      with agents that inhibit NF-kappaB or NF-AT activation. These studies demonstrate
      that HIV-1 Tat plays an important role in activating expression of HERV-K (HML-2)
      in the setting of HIV-1 infection.

PMID- 22593156
TI  - The interactome of the human respiratory syncytial virus NS1 protein highlights
      multiple effects on host cell biology.
AB  - Viral proteins can have multiple effects on host cell biology. Human respiratory
      syncytial virus (HRSV) nonstructural protein 1 (NS1) is a good example of this.
      During the virus life cycle, NS1 can act as an antagonist of host type I and III
      interferon production and signaling, inhibit apoptosis, suppress dendritic cell
      maturation, control protein stability, and regulate transcription of host cell
      mRNAs, among other functions. It is likely that NS1 performs these different
      roles through interactions with multiple host cell proteins. To investigate this
      and identify cellular proteins that could interact with NS1, we used quantitative
      proteomics in combination with green fluorescent protein (GFP)-trap
      immunoprecipitation and bioinformatic analysis. This analysis identified 221
      proteins that were potentially part of complexes that could interact with NS1,
      with many of these associated with transcriptional regulation as part of the
      mediator complex, cell cycle regulation, and other functions previously assigned
      to NS1. Specific immunoprecipitation using the GFP trap was used to confirm the
      ability of selected cellular proteins to interact individually with NS1.
      Infection of A549 cells with recombinant viruses deficient in the expression of
      NS1 and overexpression analysis both demonstrated that NS1 was necessary and
      sufficient for the enrichment of cells in the G(1) phase of the cell cycle.

PMID- 22593157
TI  - Structural analysis of hepatitis C virus core-E1 signal peptide and requirements
      for cleavage of the genotype 3a signal sequence by signal peptide peptidase.
AB  - The maturation of the hepatitis C virus (HCV) core protein requires proteolytic
      processing by two host proteases: signal peptidase (SP) and the intramembrane
      cleaving protease signal peptide peptidase (SPP). Previous work on HCV genotype
      1a (GT1a) and GT2a has identified crucial residues required for efficient signal
      peptide processing by SPP, which in turn has an effect on the production of
      infectious virus particles. Here we demonstrate that the JFH1 GT2a core-E1 signal
      peptide can be adapted to the GT3a sequence without affecting the production of
      infectious HCV. Through mutagenesis studies, we identified crucial residues
      required for core-E1 signal peptide processing, including a GT3a sequence
      specific histidine (His) at position 187. In addition, the stable knockdown of
      intracellular SPP levels in HuH-7 cells significantly affects HCV virus titers,
      further demonstrating the requirement for SPP for the maturation of core and the
      production of infectious HCV particles. Finally, our nuclear magnetic resonance
      (NMR) structural analysis of a synthetic HCV JFH1 GT2a core-E1 signal peptide
      provides an essential structural template for a further understanding of core
      processing as well as the first model for an SPP substrate within its membrane
      environment. Our findings give deeper insights into the mechanisms of
      intramembrane-cleaving proteases and the impact on viral infections.

PMID- 22593158
TI  - The structure of an archaeal viral integrase reveals an evolutionarily conserved
      catalytic core yet supports a mechanism of DNA cleavage in trans.
AB  - The first structure of a catalytic domain from a hyperthermophilic archaeal viral
      integrase reveals a minimal fold similar to that of bacterial HP1 integrase and
      defines structural elements conserved across three domains of life. However,
      structural superposition on bacterial Holliday junction complexes and
      similarities in the C-terminal tail with that of eukaryotic Flp suggest that the
      catalytic tyrosine and an additional active-site lysine are delivered to
      neighboring subunits in trans. An intramolecular disulfide bond contributes
      significant thermostability in vitro.

PMID- 22593159
TI  - Modeling the intracellular dynamics of influenza virus replication to understand
      the control of viral RNA synthesis.
AB  - Influenza viruses transcribe and replicate their negative-sense RNA genome inside
      the nucleus of host cells via three viral RNA species. In the course of an
      infection, these RNAs show distinct dynamics, suggesting that differential
      regulation takes place. To investigate this regulation in a systematic way, we
      developed a mathematical model of influenza virus infection at the level of a
      single mammalian cell. It accounts for key steps of the viral life cycle, from
      virus entry to progeny virion release, while focusing in particular on the
      molecular mechanisms that control viral transcription and replication. We
      therefore explicitly consider the nuclear export of viral genome copies (vRNPs)
      and a recent hypothesis proposing that replicative intermediates (cRNA) are
      stabilized by the viral polymerase complex and the nucleoprotein (NP). Together,
      both mechanisms allow the model to capture a variety of published data sets at an
      unprecedented level of detail. Our findings provide theoretical support for an
      early regulation of replication by cRNA stabilization. However, they also suggest
      that the matrix protein 1 (M1) controls viral RNA levels in the late phase of
      infection as part of its role during the nuclear export of viral genome copies.
      Moreover, simulations show an accumulation of viral proteins and RNA toward the
      end of infection, indicating that transport processes or budding limits virion
      release. Thus, our mathematical model provides an ideal platform for a systematic
      and quantitative evaluation of influenza virus replication and its complex
      regulation.

PMID- 22593160
TI  - Accelerated heterologous adenovirus prime-boost SIV vaccine in neonatal rhesus
      monkeys.
AB  - A pediatric human immunodeficiency virus type 1 (HIV-1) vaccine would be
      desirable to protect infants against HIV-1 transmission from breast-feeding. Such
      a vaccine would need to induce protective immunity at mucosal surfaces in
      neonates as soon as possible after birth. Recombinant adenovirus (rAd) vectors
      have been shown to elicit potent systemic and mucosal virus-specific immune
      responses in adult nonhuman primates and humans, but these vectors have not
      previously been comprehensively studied in infants. In this study, we demonstrate
      that a single injection of rAd26 encoding simian immunodeficiency virus mac239
      (SIVmac239) Gag on the day of birth elicited detectable Gag-specific cellular
      immune responses in rhesus monkeys, but these responses were transient and waned
      quickly. In contrast, an accelerated heterologous prime-boost regimen involving
      administration of rAd35 at birth and rAd26 at 4 weeks of life elicited potent and
      durable Gag-specific cellular and humoral immune responses in neonatal rhesus
      monkeys, including mucosal responses that remained detectable at 1 year of age.
      These results suggest the potential of an accelerated heterologous rAd prime
      boost regimen as a candidate HIV-1 vaccine for newborns.

PMID- 22593161
TI  - cis-Acting determinants of 7SL RNA packaging by HIV-1.
AB  - The host noncoding RNA 7SL is highly enriched in the virions of retroviruses. We
      examined the regions of 7SL that mediate packaging by HIV-1. Both the Alu domain
      and the S domain were sufficient to mediate specific packaging when expressed
      separately as truncations of 7SL. However, while the Alu domain competed with
      endogenous 7SL for packaging in proportion to Gag, the S domain was packaged
      additively, implying that the Alu and S domains are packaged via separate
      mechanisms and that the Alu domain is packaged by the same mechanism as
      endogenous 7SL. Further truncations of the Alu domain or mutation of the Alu
      domain helix 5c region significantly reduced packaging efficiency, implicating
      helix 5c as critical for packaging, reinforcing the finding that 7SL packaging is
      highly selective, and confirming that 7SL is not passively acquired.
      Surprisingly, when the Alu domain was mutated so that it no longer contained a
      binding site for the SRP protein heterodimer SRP9/14, it was no longer packaged
      in a competitive manner but instead was packaged additively with endogenous 7SL.
      These data support a model in which 7SL RNA is packaged via interactions between
      Gag and a 7SL RNA structure that exists transiently at a discrete stage of SRP
      biogenesis. Our data further indicate that a secondary "additive" pathway exists
      that can result in the packaging of certain 7SL derivatives in molar excess to
      endogenously packaged 7SL.

PMID- 22593162
TI  - A baculovirus-encoded MicroRNA (miRNA) suppresses its host miRNA biogenesis by
      regulating the exportin-5 cofactor Ran.
AB  - MicroRNAs have emerged as key players in the regulation of various biological
      processes in eukaryotes, including host-pathogen interactions. Recent studies
      suggest that viruses encode miRNAs to manipulate their host gene expression to
      ensure their effective proliferation, whereas the host limits virus infection by
      differentially expressing miRNAs that target essential viral genes. Here, we
      demonstrate that an insect virus, Bombyx mori nucleopolyhedrosis virus (BmNPV),
      modulates the small-RNA-mediated defense of its host, B. mori, by encoding an
      miRNA (bmnpv-miR-1) that downregulates the expression of the host GTP-binding
      nuclear protein Ran, an essential component of the exportin-5-mediated
      nucleocytoplasmic transport machinery mainly involved in small-RNA transport from
      the nucleus to the cytoplasm. We demonstrate the sequence-dependent interaction
      of bmnpv-miR-1 with Ran mRNA using cell culture and in vivo assays, including RNA
      interference (RNAi) of Ran. Our results clearly show that bmnpv-miR-1 represses
      Ran, leading to reduction in the host small-RNA population, and consequently, the
      BmNPV load increases in the infected larvae. Blocking of bmnpv-miR-1 resulted in
      higher expression levels of Ran and a decrease in BmNPV proliferation. In
      contrast, blockage of host miRNA, bmo-miR-8, which targets the immediate-early
      gene of the virus and whose production was repressed upon bmnpv-miR-1 and Ran
      dsRNA administration, resulted in a significant increase in the virus load in the
      infected B. mori larvae. The present study provides an insight into one of the
      evasion strategies used by the virus to counter the host defense for its
      effective proliferation and has relevance to the development of insect virus
      control strategies.

PMID- 22593163
TI  - Sequence and structural characterization of great salt lake bacteriophage CW02, a
      member of the T7-like supergroup.
AB  - Halophage CW02 infects a Salinivibrio costicola-like bacterium, SA50, isolated
      from the Great Salt Lake. Following isolation, cultivation, and purification,
      CW02 was characterized by DNA sequencing, mass spectrometry, and electron
      microscopy. A conserved module of structural genes places CW02 in the T7
      supergroup, members of which are found in diverse aquatic environments, including
      marine and freshwater ecosystems. CW02 has morphological similarities to viruses
      of the Podoviridae family. The structure of CW02, solved by cryogenic electron
      microscopy and three-dimensional reconstruction, enabled the fitting of a portion
      of the bacteriophage HK97 capsid protein into CW02 capsid density, thereby
      providing additional evidence that capsid proteins of tailed double-stranded DNA
      phages have a conserved fold. The CW02 capsid consists of bacteriophage lambda
      gpD-like densities that likely contribute to particle stability. Turret-like
      densities were found on icosahedral vertices and may represent a unique
      adaptation similar to what has been seen in other extremophilic viruses that
      infect archaea, such as Sulfolobus turreted icosahedral virus and halophage SH1.

PMID- 22593164
TI  - Expression of microRNA miR-122 facilitates an efficient replication in nonhepatic
      cells upon infection with hepatitis C virus.
AB  - Hepatitis C virus (HCV) is one of the most common etiologic agents of chronic
      liver diseases, including liver cirrhosis and hepatocellular carcinoma. In
      addition, HCV infection is often associated with extrahepatic manifestations
      (EHM), including mixed cryoglobulinemia and non-Hodgkin's lymphoma. However, the
      mechanisms of cell tropism of HCV and HCV-induced EHM remain elusive, because in
      vitro propagation of HCV has been limited in the combination of cell culture
      adapted HCV (HCVcc) and several hepatic cell lines. Recently, a liver-specific
      microRNA called miR-122 was shown to facilitate the efficient propagation of
      HCVcc in several hepatic cell lines. In this study, we evaluated the importance
      of miR-122 on the replication of HCV in nonhepatic cells. Among the nonhepatic
      cell lines expressing functional HCV entry receptors, Hec1B cells derived from
      human uterus exhibited a low level of replication of the HCV genome upon
      infection with HCVcc. Exogenous expression of miR-122 in several cells
      facilitates efficient viral replication but not production of infectious
      particles, probably due to the lack of hepatocytic lipid metabolism. Furthermore,
      expression of mutant miR-122 carrying a substitution in a seed domain was
      required for efficient replication of mutant HCVcc carrying complementary
      substitutions in miR-122-binding sites, suggesting that specific interaction
      between miR-122 and HCV RNA is essential for the enhancement of viral
      replication. In conclusion, although miR-122 facilitates efficient viral
      replication in nonhepatic cells, factors other than miR-122, which are most
      likely specific to hepatocytes, are required for HCV assembly.

PMID- 22593165
TI  - Vpu mediates depletion of interferon regulatory factor 3 during HIV infection by
      a lysosome-dependent mechanism.
AB  - HIV has evolved sophisticated mechanisms to avoid restriction by intracellular
      innate immune defenses that otherwise serve to control acute viral infection and
      virus dissemination. Innate defenses are triggered when pattern recognition
      receptor (PRR) proteins of the host cell engage pathogen-associated molecule
      patterns (PAMPs) present in viral products. Interferon regulatory factor 3 (IRF3)
      plays a central role in PRR signaling of innate immunity to drive the expression
      of type I interferon (IFN) and interferon-stimulated genes (ISGs), including a
      variety of HIV restriction factors, that serve to limit viral replication
      directly and/or program adaptive immunity. Productive infection of T cells by HIV
      is dependent upon the targeted proteolysis of IRF3 that occurs through a virus
      directed mechanism that results in suppression of innate immune defenses.
      However, the mechanisms by which HIV controls innate immune signaling and IRF3
      function are not defined. Here, we examined the innate immune response induced by
      HIV strains identified through their differential control of PRR signaling. We
      identified viruses that, unlike typical circulating HIV strains, lack the ability
      to degrade IRF3. Our studies show that IRF3 regulation maps specifically to the
      HIV accessory protein Vpu. We define a molecular interaction between Vpu and IRF3
      that redirects IRF3 to the endolysosome for proteolytic degradation, thus
      allowing HIV to avoid the innate antiviral immune response. Our studies reveal
      that Vpu is an important IRF3 regulator that supports acute HIV infection through
      innate immune suppression. These observations define the Vpu-IRF3 interface as a
      novel target for therapeutic strategies aimed at enhancing the immune response to
      HIV.

PMID- 22593166
TI  - Structural insight into African horsesickness virus infection.
AB  - African horsesickness (AHS) is a devastating disease of horses. The disease is
      caused by the double-stranded RNA-containing African horsesickness virus (AHSV).
      Using electron cryomicroscopy and three-dimensional image reconstruction, we
      determined the architecture of an AHSV serotype 4 (AHSV-4) reference strain. The
      structure revealed triple-layered AHS virions enclosing the segmented genome and
      transcriptase complex. The innermost protein layer contains 120 copies of VP3,
      with the viral polymerase, capping enzyme, and helicase attached to the inner
      surface of the VP3 layer on the 5-fold axis, surrounded by double-stranded RNA.
      VP7 trimers form a second, T=13 layer on top of VP3. Comparative analyses of the
      structures of bluetongue virus and AHSV-4 confirmed that VP5 trimers form
      globular domains and VP2 trimers form triskelions, on the virion surface. We also
      identified an AHSV-7 strain with a truncated VP2 protein (AHSV-7 tVP2) which
      outgrows AHSV-4 in culture. Comparison of AHSV-7 tVP2 to bluetongue virus and
      AHSV-4 allowed mapping of two domains in AHSV-4 VP2, and one in bluetongue virus
      VP2, that are important in infection. We also revealed a protein plugging the 5
      fold vertices in AHSV-4. These results shed light on virus-host interactions in
      an economically important orbivirus to help the informed design of new vaccines.

PMID- 22593167
TI  - Characterization of hepatitis E virus recombinant ORF2 proteins expressed by
      vaccinia viruses.
AB  - Hepatitis E virus (HEV), an enterically transmitted pathogen, is one of the major
      causes of acute hepatitis in humans worldwide, being responsible for outbreaks
      and epidemics in regions with suboptimal sanitary conditions, in many of which it
      is endemic. In industrialized countries, hepatitis E is rarely reported, but
      recent studies have revealed quite high human seroprevalence rates and the
      possibility of porcine zoonotic transmission. There is currently no specific
      therapy or licensed vaccine against HEV infection, and little is known about its
      intracellular growth cycle, as until very recently no efficient cell culture
      system has been available. In the present study, vaccinia viruses have been used
      to express recombinant HEV ORF2 proteins, allowing the study of their
      glycosylation patterns and subcellular localization. Furthermore, the expressed
      proteins have been shown to be good antigens for diagnostic purposes and to
      elicit high and long-lasting specific anti-HEV titers of antibodies in mice that
      are passively transferred to the offspring by both transplacental and lactation
      routes.

PMID- 22593169
TI  - Cryphonectria nitschkei virus 1 structure shows that the capsid protein of
      chrysoviruses is a duplicated helix-rich fold conserved in fungal double-stranded
      RNA viruses.
AB  - Cryoelectron microscopy reconstruction of Cryphonectria nitschkei virus 1, a
      double-stranded RNA (dsRNA) virus, shows that the capsid protein (60
      copies/particle) is formed by a repeated helical core, indicative of gene
      duplication. This unusual organization is common to chrysoviruses. The
      arrangement of many of these putative alpha-helices is conserved in the totivirus
      L-A capsid protein, suggesting a shared motif. Our results indicate that a 120
      subunit T=1 capsid is a conserved architecture that optimizes dsRNA replication
      and organization.

PMID- 22593168
TI  - Marek's disease virus expresses multiple UL44 (gC) variants through mRNA splicing
      that are all required for efficient horizontal transmission.
AB  - Marek's disease (MD) is a devastating oncogenic viral disease of chickens caused
      by Gallid herpesvirus 2, or MD virus (MDV). MDV glycoprotein C (gC) is encoded by
      the alphaherpesvirus UL44 homolog and is essential for the horizontal
      transmission of MDV (K. W. Jarosinski and N. Osterrieder, J. Virol. 84:7911-7916,
      2010). Alphaherpesvirus gC proteins are type 1 membrane proteins and are
      generally anchored in cellular membranes and the virion envelope by a short
      transmembrane domain. However, the majority of MDV gC is secreted in vitro,
      although secondary-structure analyses predict a carboxy-terminal transmembrane
      domain. In this report, two alternative mRNA splice variants were identified by
      reverse transcription (RT)-PCR analyses, and the encoded proteins were predicted
      to specify premature stop codons that would lead to gC proteins that lack the
      transmembrane domain. Based on the size of the intron removed for each UL44 (gC)
      transcript, they were termed gC104 and gC145. Recombinant MDV viruses were
      generated in which only full-length viral gC (vgCfull), gC104 (vgC104), or gC145
      (vgC145) was expressed. Predictably, gCfull was expressed predominantly as a
      membrane-associated protein, while both gC104 and gC145 were secreted, suggesting
      that the dominant gC variants expressed in vitro are the spliced variants. In
      experimentally infected chickens, the expression of each of the gC variants
      individually did not alter replication or disease induction. However, horizontal
      transmission was reduced compared to that of wild-type or revertant viruses when
      the expression of only a single gC was allowed, indicating that all three forms
      of gC are required for the efficient transmission of MDV in chickens.

PMID- 22593170
TI  - A single mutation in the glycophorin A binding site of hepatitis A virus enhances
      virus clearance from the blood and results in a lower fitness variant.
AB  - Hepatitis A virus (HAV) has previously been reported to bind to human red blood
      cells through interaction with glycophorin A. Residue K221 of VP1 and the
      surrounding VP3 residues are involved in such an interaction. This capsid region
      is specifically recognized by the monoclonal antibody H7C27. A monoclonal
      antibody-resistant mutant with the mutation G1217D has been isolated. In the
      present study, the G1217D mutant was characterized physically and biologically in
      comparison with the parental HM175 43c strain. The G1217D mutant is more
      sensitive to acid pH and binds more efficiently to human and rat erythrocytes
      than the parental 43c strain. In a rat model, it is eliminated from serum more
      rapidly and consequently reaches the liver with a certain delay compared to the
      parental 43c strain. In competition experiments performed in vivo in the rat
      model, the G1217D mutant was efficiently outcompeted by the parental 43c strain.
      Only in the presence of antibodies reacting specifically with the parental 43c
      strain could the G1217D mutant outcompete the parental 43c strain in serum,
      although the latter still showed a remarkable ability to reach the liver.
      Altogether, these results indicate that the G1217D mutation induces a low fitness
      phenotype which could explain the lack of natural antigenic variants of the
      glycophorin A binding site.

PMID- 22593171
TI  - APOE epsilon4 status and traumatic brain injury on the gridiron or the
      battlefield.

PMID- 22593172
TI  - Drug-based optical agents: infiltrating clinics at lower risk.
AB  - Fluorescent agents with specificity to cellular and subcellular moieties present
      promise for enhancing diagnostics and theranostics, yet challenges associated
      with regulatory approvals of experimental agents stifle the clinical translation.
      As a result, targeted fluorescent agents have remained predominantly as
      preclinical imaging tools. We discuss the potential of using optically labeled
      drugs to accelerate the clinical acceptance of optical and optoacoustic agents,
      in analogy to nuclear medicine approaches. This strategy, corroborated with
      microdosing studies, outlines a promising approach for overcoming bottlenecks and
      advancing photonic clinical imaging.

PMID- 22593174
TI  - Gene therapy for aromatic L-amino acid decarboxylase deficiency.
AB  - Aromatic L-amino acid decarboxylase (AADC) is required for the synthesis of the
      neurotransmitters dopamine and serotonin. Children with defects in the AADC gene
      show compromised development, particularly in motor function. Drug therapy has
      only marginal effects on some of the symptoms and does not change early childhood
      mortality. Here, we performed adeno-associated viral vector-mediated gene
      transfer of the human AADC gene bilaterally into the putamen of four patients 4
      to 6 years of age. All of the patients showed improvements in motor performance:
      One patient was able to stand 16 months after gene transfer, and the other three
      patients achieved supported sitting 6 to 15 months after gene transfer. Choreic
      dyskinesia was observed in all patients, but this resolved after several months.
      Positron emission tomography revealed increased uptake by the putamen of 6
      [(18)F]fluorodopa, a tracer for AADC. Cerebrospinal fluid analysis showed
      increased dopamine and serotonin levels after gene transfer. Thus, gene therapy
      targeting primary AADC deficiency is well tolerated and leads to improved motor
      function.

PMID- 22593173
TI  - Chronic traumatic encephalopathy in blast-exposed military veterans and a blast
      neurotrauma mouse model.
AB  - Blast exposure is associated with traumatic brain injury (TBI), neuropsychiatric
      symptoms, and long-term cognitive disability. We examined a case series of
      postmortem brains from U.S. military veterans exposed to blast and/or concussive
      injury. We found evidence of chronic traumatic encephalopathy (CTE), a tau
      protein-linked neurodegenerative disease, that was similar to the CTE
      neuropathology observed in young amateur American football players and a
      professional wrestler with histories of concussive injuries. We developed a blast
      neurotrauma mouse model that recapitulated CTE-linked neuropathology in wild-type
      C57BL/6 mice 2 weeks after exposure to a single blast. Blast-exposed mice
      demonstrated phosphorylated tauopathy, myelinated axonopathy, microvasculopathy,
      chronic neuroinflammation, and neurodegeneration in the absence of macroscopic
      tissue damage or hemorrhage. Blast exposure induced persistent hippocampal
      dependent learning and memory deficits that persisted for at least 1 month and
      correlated with impaired axonal conduction and defective activity-dependent long
      term potentiation of synaptic transmission. Intracerebral pressure recordings
      demonstrated that shock waves traversed the mouse brain with minimal change and
      without thoracic contributions. Kinematic analysis revealed blast-induced head
      oscillation at accelerations sufficient to cause brain injury. Head
      immobilization during blast exposure prevented blast-induced learning and memory
      deficits. The contribution of blast wind to injurious head acceleration may be a
      primary injury mechanism leading to blast-related TBI and CTE. These results
      identify common pathogenic determinants leading to CTE in blast-exposed military
      veterans and head-injured athletes and additionally provide mechanistic evidence
      linking blast exposure to persistent impairments in neurophysiological function,
      learning, and memory.

PMID- 22593175
TI  - CD25 blockade depletes and selectively reprograms regulatory T cells in concert
      with immunotherapy in cancer patients.
AB  - Regulatory T cells (T(regs)) are key mediators of immune tolerance and feature
      prominently in cancer. Depletion of CD25(+) FoxP3(+) T(regs) in vivo may promote
      T cell cancer immunosurveillance, but no strategy to do so in humans while
      preserving immunity and preventing autoimmunity has been validated. We evaluated
      the Food and Drug Administration-approved CD25-blocking monoclonal antibody
      daclizumab with regard to human T(reg) survival and function. In vitro,
      daclizumab did not mediate antibody-dependent or complement-mediated cytotoxicity
      but rather resulted in the down-regulation of FoxP3 selectively among CD25(high)
      CD45RA(neg) T(regs). Moreover, daclizumab-treated CD45RA(neg) T(regs) lost
      suppressive function and regained the ability to produce interferon-gamma,
      consistent with reprogramming. To understand the impact of daclizumab on T(regs)
      in vivo, we performed a clinical trial of daclizumab in combination with an
      experimental cancer vaccine in patients with metastatic breast cancer. Daclizumab
      administration led to a marked and prolonged decrease in T(regs) in patients.
      Robust CD8 and CD4 T cell priming and boosting to all vaccine antigens were
      observed in the absence of autoimmunity. We conclude that CD25 blockade depletes
      and selectively reprograms T(regs) in concert with active immune therapy in
      cancer patients. These results suggest a mechanism to target cancer-associated
      T(regs) while avoiding autoimmunity.

PMID- 22593176
TI  - High-throughput sequencing detects minimal residual disease in acute T
      lymphoblastic leukemia.
AB  - High-throughput sequencing (HTS) of lymphoid receptor genes is an emerging
      technology that can comprehensively assess the diversity of the immune system.
      Here, we applied HTS to the diagnosis of T-lineage acute lymphoblastic
      leukemia/lymphoma. Using 43 paired patient samples, we then assessed minimal
      residual disease (MRD) at day 29 after treatment. The variable regions of TCRB
      and TCRG were sequenced using an Illumina HiSeq platform after performance of
      multiplexed polymerase chain reaction, which targeted all potential V-J
      rearrangement combinations. Pretreatment samples were used to define clonal T
      cell receptor (TCR) complementarity-determining region 3 (CDR3) sequences, and
      paired posttreatment samples were evaluated for MRD. Abnormal T lymphoblast
      identification by multiparametric flow cytometry was concurrently performed for
      comparison. We found that TCRB and TCRG HTS not only identified clonality at
      diagnosis in most cases (31 of 43 for TCRB and 27 of 43 for TCRG) but also
      detected subsequent MRD. As expected, HTS of TCRB and TCRG identified MRD that
      was not detected by flow cytometry in a subset of cases (25 of 35 HTS compared
      with 13 of 35, respectively), which highlights the potential of this technology
      to define lower detection thresholds for MRD that could affect clinical treatment
      decisions. Thus, next-generation sequencing of lymphoid receptor gene repertoire
      may improve clinical diagnosis and subsequent MRD monitoring of
      lymphoproliferative disorders.

PMID- 22593178
TI  - Rationality, religion and refusal of treatment in an ambulance revisited.
AB  - In their recent article, Erbay et al considered whether a seriously injured
      patient should be able to refuse treatment if the refusal was based on a
      (mis)interpretation of religious doctrine. They argued that in such a case 'what
      is important...is whether the teaching or philosophy used as a reference point
      has been in fact correctly perceived' (p 653). If it has not been, they asserted
      that this eroded the patient's capacity to make an autonomous decision and that
      therefore, in such cases, it is the role of the healthcare professional (HCP) to
      'assist patients to think more clearly and rationally' (p 653). There are,
      however, a number of problems with the reasons why Erbay et al suggest we should
      help patients to rationalise their decisions and how HCPs should go about this.
      In this article, the author explores some of their main arguments regarding
      consent and rationality (particularly in relation to religious beliefs), as well
      as Erbay et al's normative claim that HCPs have an obligation to promote autonomy
      by helping patients to come to a 'rational' decision. Ultimately, the author
      agrees that the (temporary) solution to the dilemma presented in this scenario
      (which was to insert an intravenous cannula into the patient in order to allow an
      infusion of fluids in the event that he changed his mind) seemed both pragmatic
      and ethically permissible. However, it is suggested that the arguments which
      underpin this conclusion in Erbay et al's article are largely unsound. 

PMID- 22593177
TI  - Chemical visualization of phosphoproteomes on membrane.
AB  - With new discoveries of important roles of phosphorylation on a daily basis,
      phospho-specific antibodies, as the primary tool for on-membrane detection of
      phosphoproteins, face enormous challenges. To address an urgent need for
      convenient and reliable analysis of phosphorylation events, we report a novel
      strategy for sensitive phosphorylation analysis in the Western blotting format.
      The chemical reagent, which we termed pIMAGO, is based on a multifunctionalized
      soluble nanopolymer and is capable of selectively binding to phosphorylated
      residues independent of amino acid microenvironment, thus offering great promise
      as a universal tool in biological analyses where the site of phosphorylation is
      not known or its specific antibody is not available. The specificity and
      sensitivity of the approach was first examined using a mixture of standard
      proteins. The method was then applied to monitor phosphorylation changes in in
      vitro kinase and phosphatase assays. Finally, to demonstrate the unique ability
      of pIMAGO to measure endogenous phosphorylation, we used it to visualize and
      determine the differences in phosphorylated proteins that interact with wild-type
      and kinase dead mutant of Polo-like kinase 1 during mitosis, the results of which
      were further confirmed by a quantitative phosphoproteomics experiment.

PMID- 22593179
TI  - Implications of congenital heart disease in 2012.

PMID- 22593180
TI  - Postreperfusion syndrome during liver transplantation.

PMID- 22593181
TI  - A local paracrine and endocrine network involving TGFbeta, Cox-2, ROS, and
      estrogen receptor beta influences reactive stromal cell regulation of prostate
      cancer cell motility.
AB  - The tumor microenvironment plays a critical role in supporting cancer cells
      particularly as they disengage from limitations on their growth and motility
      imposed by surrounding nonreactive stromal cells. We show here that stromal
      derived androgenic precursors are metabolized by DU145 human prostate cancer
      (PCa) cells to generate ligands for estrogen receptor-beta, which act to limit
      their motility through transcriptional regulation of E-cadherin. Although primary
      human PCa-associated fibroblasts and the human WPMY-1-reactive prostate stromal
      cell line maintain this inherent estrogen receptor (ER)beta-dependent motility
      inhibitor activity, they are subverted by TGF-beta1 pro-oxidant signals derived
      from cocultured DU145 PCa cells. Specifically, stromal-produced H(2)O(2), which
      requires Cox-2, acts as a second paracrine factor to inhibit ERbeta activity in
      adjacent DU145 cells. Chromatin immunoprecipitation analysis reveals that ERbeta
      recruitment to the E-cadherin promoter is inhibited when H(2)O(2) is present.
      Both neutralization of H(2)O(2) with catalase and prevention of its production by
      silencing Cox-2 expression in stromal cells restore the motility-suppression
      activity of stromal-derived ERbeta ligand precursors. These data suggest that
      reactive stromal cells may still have a capacity to limit cancer cell motility
      through a local endocrine network but must be protected from pro-oxidant signals
      triggered by cancer cell-derived TGF-beta1 to exhibit this cancer-suppressive
      function.

PMID- 22593184
TI  - Is a radially self-expanding valved stent with neochordal support enough for
      better fixation in the mitral position?

PMID- 22593182
TI  - Transactivation of microRNA-383 by steroidogenic factor-1 promotes estradiol
      release from mouse ovarian granulosa cells by targeting RBMS1.
AB  - Our previous studies have shown that microRNA-383 (miR-383) is one of the most
      down-regulated miRNA in TGF-beta1-treated mouse ovarian granulosa cells (GC).
      However, the roles and mechanisms of miR-383 in GC function during follicular
      development remain unknown. In this study, we found that miR-383 was mainly
      expressed in GC and oocytes of mouse ovarian follicles. Overexpression of miR-383
      enhanced estradiol release from GC through targeting RNA binding motif, single
      stranded interacting protein 1 (RBMS1). miR-383 inhibited RBMS1 by affecting its
      mRNA stability, which subsequently suppressed the level of c-Myc (a downstream
      target of RBMS1). Forced expression of RBMS1 or c-Myc attenuated miR-383-mediated
      steroidogenesis-promoting effects. Knockdown of the transcription factor
      steroidogenic factor-1 (SF-1) significantly suppressed the expression of
      Sarcoglycan zeta (SGCZ) (miR-383 host gene), primary and mature miR-383 in GC,
      indicating that miR-383 was transcriptionally regulated by SF-1. Luciferase and
      chromatin immunoprecipitation assays revealed that SF-1 specifically bound to the
      promoter region of SGCZ and directly transactivated miR-383 in parallel with
      SGCZ. In addition, SF-1 was involved in regulation of miR-383- and RBMS1/c-Myc
      mediated estradiol release from GC. These results suggest that miR-383 functions
      to promote steroidogenesis by targeting RBMS1, at least in part, through
      inactivation of c-Myc. SF-1 acts as a positive regulator of miR-383 processing
      and function in GC. Understanding of regulation of miRNA biogenesis and function
      in estrogen production will potentiate the usefulness of miRNA in the control of
      reproduction and treatment of some steroid-related disorders.

PMID- 22593183
TI  - Characterization of follistatin-type domains and their contribution to myostatin
      and activin A antagonism.
AB  - Follistatin (FST)-type proteins are important antagonists of some members of the
      large TGF-beta family of cytokines. These include myostatin, an important
      negative regulator of muscle growth, and the closely related activin A, which is
      involved in many physiological functions, including maintenance of a normal
      reproductive axis. FST-type proteins, including FST and FST-like 3 (FSTL3),
      differentially inhibit various TGF-beta family ligands by binding each ligand
      with two FST-type molecules. In this study, we sought to examine features that
      are important for ligand antagonism by FST-type proteins. Previous work has shown
      that a modified construct consisting of the FST N-terminal domain (ND) followed
      by two repeating follistatin domains (FSD), herein called FST ND-FSD1-FSD1,
      exhibits strong specificity for myostatin over activin A. Using cell-based
      assays, we show that FST ND-FSD1-FSD1 is unique in its specificity for myostatin
      as compared with similar constructs containing domains from FSTL3 and that the ND
      is critical to its activity. Furthermore, we demonstrate that FSD3 of FST
      provides affinity to ligand inhibition and confers resistance to perturbations in
      the ND and FSD2, likely through the interaction of FSD3 of one FST molecule with
      the ND of the other FST molecule. Additionally, our data suggest that this
      contact provides cooperativity to ligand antagonism. Cross-linking studies show
      that this interaction also potentiates formation of 1:2 ligand-FST complexes,
      whereas lack of FSD3 allows formation of 1:1 complexes. Altogether, these studies
      support that domain differences generate FST-type molecules that are each
      uniquely suited ligand antagonists.

PMID- 22593185
TI  - The clinical outcome of non-small cell lung cancer patients with adjacent lobe
      invasion: the optimal classification according to the status of the interlobar
      pleura at the invasion point.
AB  - OBJECTIVES: The aim of this study was to analyse the survival of non-small cell
      lung cancer (NSCLC) patients with adjacent lobe invasion (ALI) with emphasis on
      the interlobar fissure status at the tumour invasion point. METHODS: We
      retrospectively evaluated 2097 consecutive patients with surgically resected
      NSCLC from July 1993 through April 2006. Of these, 90 (4.3%) patients had tumours
      with ALI. We divided ALIs into two types by histological examination using
      elastic stains: direct ALI beyond the incomplete fissure (ALI-D, n = 18) and ALI
      across the interlobar fissure (ALI-A, n = 72), and compared the
      clinicopathological features and survival. RESULTS: The patients with ALI
      demonstrated an intermediate survival between T2a and T2b tumours (5-year overall
      survival: T2a, 61.0%; ALI, 59.6%; T2b, 49.2%). There were distinct survival
      differences between the patients with ALI-A and ALI-D (5-year overall survival:
      ALI-D, 85.7%; ALI-A, 52.0%; P = 0.010). The survival of patients with ALI-A was
      not statistically different from that of patients with T2b tumours, regardless of
      the tumour size (P = 0.846). The survival of the patients with ALI-D did not
      statistically differ from those with T1a or T1b tumours (P = 0.765 and 0.418,
      respectively). CONCLUSIONS: Our results indicate that the interlobar fissure
      status affects the survival of the patients with ALI. ALI should be examined by
      elastic stains and only ALI-A should be classified as true ALI. We propose that
      ALI-A tumours with a size of <= 5 cm should be assigned to T2b, but ALI-D tumours
      do not require an adjustment of the T descriptor.

PMID- 22593186
TI  - Special issue marking 40 years of the MSc Medical Statistics at the London School
      of Hygiene & Tropical Medicine.

PMID- 22593187
TI  - Integrin alpha5beta1 plays a critical role in resistance to temozolomide by
      interfering with the p53 pathway in high-grade glioma.
AB  - Integrins play a role in the resistance of advanced cancers to radiotherapy and
      chemotherapy. In this study, we show that high expression of the alpha5 integrin
      subunit compromises temozolomide-induced tumor suppressor p53 activity in human
      glioblastoma cells. We found that depletion of the alpha5 integrin subunit
      increased p53 activity and temozolomide sensitivity. However, when cells were
      treated with the p53 activator nutlin-3a, the protective effect of alpha5
      integrin on p53 activation and cell survival was lost. In a functional p53
      background, nutlin-3a downregulated the alpha5 integrin subunit, thereby
      increasing the cytotoxic effect of temozolomide. Clinically, alpha5beta1 integrin
      expression was associated with a more aggressive phenotype in brain tumors, and
      high alpha5 integrin gene expression was associated with decreased survival of
      patients with high-grade glioma. Taken together, our findings indicate that
      negative cross-talk between alpha5beta1 integrin and p53 supports glioma
      resistance to temozolomide, providing preclinical proof-of-concept that
      alpha5beta1 integrin represents a therapeutic target for high-grade brain tumors.
      Direct activation of p53 may remain a therapeutic option in the subset of
      patients with high-grade gliomas that express both functional p53 and a high
      level of alpha5beta1 integrin.

PMID- 22593188
TI  - Deletion of the endothelial Bmx tyrosine kinase decreases tumor angiogenesis and
      growth.
AB  - Bmx, [corrected] also known as Etk, is a member of the Tec family of nonreceptor
      tyrosine kinases. Bmx is expressed mainly in arterial endothelia and in myeloid
      hematopoietic cells. Bmx regulates ischemia-mediated arteriogenesis and
      lymphangiogenesis, but its role in tumor angiogenesis is not known. In this
      study, we characterized the function of Bmx in tumor growth using both Bmx
      knockout and transgenic mice. Isogenic colon, lung, and melanoma tumor
      xenotransplants showed reductions in growth and tumor angiogenesis in Bmx gene
      deleted ((-/-)) mice, whereas developmental angiogenesis was not affected. In
      addition, growth of transgenic pancreatic islet carcinomas and intestinal
      adenomas was also slower in Bmx(-/-) mice. Knockout mice showed high levels of
      Bmx expression in endothelial cells of tumor-associated and peritumoral arteries.
      Moreover, endothelial cells lacking Bmx showed impaired phosphorylation of
      extracellular signal-regulated kinase (Erk) upon VEGF stimulation, indicating
      that Bmx contributes to the transduction of vascular endothelial growth factor
      signals. In transgenic mice overexpressing Bmx in epidermal keratinocytes, tumors
      induced by a two-stage chemical skin carcinogenesis treatment showed increased
      growth and angiogenesis. Our findings therefore indicate that Bmx activity
      contributes to tumor angiogenesis and growth.

PMID- 22593189
TI  - miR-103/107 promote metastasis of colorectal cancer by targeting the metastasis
      suppressors DAPK and KLF4.
AB  - Metastasis is the major cause of poor prognosis in colorectal cancer (CRC), and
      increasing evidence supports the contribution of miRNAs to cancer progression.
      Here, we found that high expression of miR-103 and miR-107 (miR-103/107) was
      associated with metastasis potential of CRC cell lines and poor prognosis in
      patients with CRC. We showed that miR-103/107 targeted the known metastasis
      suppressors death-associated protein kinase (DAPK) and Kruppel-like factor 4
      (KLF4) in CRC cells, resulting in increased cell motility and cell-matrix
      adhesion and decreased cell-cell adhesion and epithelial marker expression. miR
      103/107 expression was increased in the presence of hypoxia, thereby potentiating
      DAPK and KLF4 downregulation and hypoxia-induced motility and invasiveness. In
      mouse models of CRC, miR-103/107 overexpression potentiated local invasion and
      liver metastasis effects, which were suppressed by reexpression of DAPK or KLF4.
      miR-103/107-mediated downregulation of DAPK and KLF4 also enabled the
      colonization of CRC cells at a metastatic site. Clinically, the signature of a
      miR-103/107 high, DAPK low, and KLF4 low expression profile correlated with the
      extent of lymph node and distant metastasis in patients with CRC and served as a
      prognostic marker for metastasis recurrence and poor survival. Our findings
      therefore indicate that miR-103/107-mediated repression of DAPK and KLF4 promotes
      metastasis in CRC, and this regulatory circuit may contribute in part to hypoxia
      stimulated tumor metastasis. Strategies that disrupt this regulation might be
      developed to block CRC metastasis.

PMID- 22593190
TI  - NF-kappaB hyperactivation in tumor tissues allows tumor-selective reprogramming
      of the chemokine microenvironment to enhance the recruitment of cytolytic T
      effector cells.
AB  - Tumor infiltration with effector CD8(+) T cells (T(eff)) predicts longer
      recurrence-free survival in many types of human cancer, illustrating the broad
      significance of T(eff) for effective immunosurveillance. Colorectal tumors with
      reduced accumulation of T(eff) express low levels of T(eff)-attracting chemokines
      such as CXCL10/IP10 and CCL5/RANTES. In this study, we investigated the
      feasibility of enhancing tumor production of T(eff)-attracting chemokines as a
      cancer therapeutic strategy using a tissue explant culture system to analyze
      chemokine induction in intact tumor tissues. In different tumor explants, we
      observed highly heterogeneous responses to IFNalpha or poly-I:C (a TLR3 ligand)
      when they were applied individually. In contrast, a combination of IFNalpha and
      poly-I:C uniformly enhanced the production of CXCL10 and CCL5 in all tumor
      lesions. Moreover, these effects could be optimized by the further addition of
      COX inhibitors. Applying this triple combination also uniformly suppressed the
      production of CCL22/MDC, a chemokine associated with infiltration of T regulatory
      cells (T(reg)). The T(eff)-enhancing effects of this treatment occurred
      selectively in tumor tissues, as compared with tissues derived from tumor
      margins. These effects relied on the increased propensity of tumor-associated
      cells (mostly fibroblasts and infiltrating inflammatory cells) to hyperactivate
      NF-kappaB and produce T(eff)-attracting chemokines in response to treatment,
      resulting in an enhanced ability of the treated tumors to attract T(eff) cells
      and reduced ability to attract T(reg) cells. Together, our findings suggest the
      feasibility of exploiting NF-kappaB hyperactivation in the tumor microenvironment
      to selectively enhance T(eff) entry into colon tumors.

PMID- 22593191
TI  - Numb regulates stability and localization of the mitotic kinase PLK1 and is
      required for transit through mitosis.
AB  - Numb functions in progenitor cell fate determination and early development, but
      it is also expressed in postdevelopmental tissues and cancers where its role is
      unclear. In this study, we report that a targeted knockdown of Numb expression
      causes a G(2)-M arrest and reduced cell growth in human melanoma cells. Co
      immunoprecipitation and colocalization studies showed that Numb interacts with
      the serine/threonine polo-like kinase Plk1 and Numb cycles in a cell-cycle
      dependent fashion along with this mitotic regulator. Interestingly, Numb
      expression was required for Plk1 protein stability and localization to the
      spindle poles during mitosis. Reduction in Numb expression resulted in
      mislocalization of Plk1 at both metaphase and anaphase, leading to disorganized
      gamma-tubulin recruitment in centrosomes. Together, our findings present a novel
      function for Numb during symmetric cell division. We suggest that dysregulation
      of Numb expression results in mislocalized Plk1 and poor centrosomal gamma
      tubulin recruitment, potentially contributing to mitotic errors, aneuploidy, and
      cancer development.

PMID- 22593192
TI  - Cancer angiogenesis induced by Kaposi sarcoma-associated herpesvirus is mediated
      by EZH2.
AB  - EZH2 is a component of the epigenetic regulator PRC2 that suppresses gene
      expression. Elevated expression of EZH2 is common in human cancers and is
      associated with tumor progression and poor prognosis. In this study, we show that
      EZH2 elevation is associated with epigenetic modifications of Kaposi sarcoma
      associated herpesvirus (KSHV), an oncogenic virus that promotes the development
      of Kaposi sarcoma and other malignancies that occur in patients with chronic HIV
      infections. KSHV induction of EZH2 expression was essential for KSHV-induced
      angiogenesis. High expression of EZH2 was observed in Kaposi sarcoma tumors. In
      cell culture, latent KSHV infection upregulated the expression of EZH2 in human
      endothelial cells through the expression of vFLIP and LANA, two KSHV-latent genes
      that activate the NF-kappaB pathway. KSHV-mediated upregulation of EZH2 was
      required for the induction of Ephrin-B2, an essential proangiogenic factor that
      drives endothelial cell tubule formation. Taken together, our findings indicate
      that KSHV regulates the host epigenetic modifier EZH2 to promote angiogenesis.

PMID- 22593193
TI  - ZNF217 is a marker of poor prognosis in breast cancer that drives epithelial
      mesenchymal transition and invasion.
AB  - The Kruppel-like zinc finger protein ZNF217 is a candidate oncogene in breast
      cancer. In this study, we showed that high levels of expression of ZNF217 mRNA
      are associated with poor prognosis and the development of metastases in breast
      cancer. Overexpression of ZNF217 in breast cancer cells stimulated migration and
      invasion in vitro and promoted the development of spontaneous lung or node
      metastases in mice in vivo. ZNF217 also promoted epithelial-mesenchymal
      transition (EMT) in human mammary epithelial cells, and the TGF-beta-activated
      Smad signaling pathway was identified as a major driver of ZNF217-induced EMT. In
      addition, a TGF-beta autocrine loop sustained activation of the TGF-beta pathway
      in ZNF217-overexpressing mammary epithelial cells, most likely because of ZNF217
      mediated direct upregulation of TGFB2 or TGFB3. Inhibition of the TGF-beta
      pathway led to the reversal of ZNF217-mediated EMT. Together, our findings
      indicate that ZNF217 mRNA expression may represent a novel prognostic biomarker
      in breast cancer. Therapeutic targeting of ZNF217 of the TGF-beta signaling
      pathway may benefit the subset of patients whose tumors express high levels of
      ZNF217.

PMID- 22593194
TI  - Genetically engineered mouse models: closing the gap between preclinical data and
      trial outcomes.
AB  - The high failure rate of late-stage human clinical trials, particularly in
      oncology, predicates the need for improved translation of preclinical data from
      mouse tumor models into clinical predictions. Genetically engineered mouse models
      (GEMM) may fulfill this need, because they mimic spontaneous and autochthonous
      disease progression. Using oncogenic Kras-driven GEMMs of lung and pancreatic
      adenocarcinoma, we recently showed that these models can closely phenocopy human
      therapeutic responses to standard-of-care treatment regimens. Here we review the
      successful preclinical application of such GEMMs, as well as the potential for
      discovering predictive biomarkers and gaining mechanistic insights into clinical
      outcomes and drug resistance in human cancers.

PMID- 22593195
TI  - Targeting Taspase1 for cancer therapy--letter.

PMID- 22593196
TI  - The RASSF3 candidate tumor suppressor induces apoptosis and G1-S cell-cycle
      arrest via p53.
AB  - RASSF3 is the smallest member of the RASSF family of proteins that function as
      tumor suppressors. Unlike other members of this important family, the mechanisms
      through which RASSF3 suppresses tumor formation remain unknown. Here, we show
      that RASSF3 expression induces p53-dependent apoptosis and its depletion
      attenuates DNA damage-induced apoptosis. We found that RASSF3-induced apoptosis
      depended upon p53 expression. Exogenous expression of RASSF3 induced G(1)-S
      arrest, which was also p53 dependent. In contrast, loss of RASSF3 promoted cell
      cycle progression, abrogated UVB- and VP-16-induced G(1)-S arrest, decreased p53
      protein and target gene expression, and prevented DNA repair. RASSF3 was shown to
      directly interact with and facilitate the ubiquitination of MDM2, the E3 ligase
      that targets p53 for degradation, thereby increasing p53 stabilization. Together,
      our findings show the tumor suppressor activity of RASSF3, which occurs through
      p53 stabilization and regulation of apoptosis and the cell cycle.

PMID- 22593197
TI  - The changing view of high-grade serous ovarian cancer.
AB  - The classification of epithelial ovarian cancer has been substantially revised,
      with an increased appreciation of the cellular origins and molecular aberrations
      of the different histotypes. Distinct patterns of signaling-pathway disruption
      are seen between and within histotypes. Large-scale genomic studies of high-grade
      serous cancer, the most common histotype, have identified novel molecular
      subtypes that are associated with distinct biology and clinical outcome. High
      grade serous cancers are characterized by few driver point mutations but abundant
      DNA copy number aberrations. Inactivation of genes associated with DNA damage
      repair underlies responses to platinum and PARP inhibitors. Here we review these
      recent developments.

PMID- 22593198
TI  - Modulation of microenvironment acidity reverses anergy in human and murine tumor
      infiltrating T lymphocytes.
AB  - Stimulating the effector functions of tumor-infiltrating T lymphocytes (TIL) in
      primary and metastatic tumors could improve active and adoptive T-cell therapies
      for cancer. Abnormal glycolysis, high lactic acid production, proton
      accumulation, and a reversed intra-extracellular pH gradient are thought to help
      render tumor microenvironments hostile to roving immune cells. However, there is
      little knowledge about how acidic microenvironments affect T-cell immunity. Here,
      we report that lowering the environmental pH to values that characterize tumor
      masses (pH 6-6.5) was sufficient to establish an anergic state in human and mouse
      tumor-specific CD8(+) T lymphocytes. This state was characterized by impairment
      of cytolytic activity and cytokine secretion, reduced expression of IL-2Ralpha
      (CD25) and T-cell receptors (TCR), and diminished activation of STAT5 and
      extracellular signal-regulated kinase (ERK) after TCR activation. In contrast,
      buffering pH at physiologic values completely restored all these metrics of T
      cell function. Systemic treatment of B16-OVA-bearing mice with proton pump
      inhibitors (PPI) significantly increased the therapeutic efficacy of both active
      and adoptive immunotherapy. Our findings show that acidification of the tumor
      microenvironment acts as mechanism of immune escape. Furthermore, they illustrate
      the potential of PPIs to safely correct T-cell dysfunction and improve the
      efficacy of T-cell-based cancer treatments.

PMID- 22593201
TI  - Rapamycin and thrombosis.

PMID- 22593200
TI  - In vivo alterations in cardiac metabolism and function in the spontaneously
      hypertensive rat heart.
AB  - AIMS: The aim of this work was to use hyperpolarized carbon-13 ((13)C) magnetic
      resonance (MR) spectroscopy and cine MR imaging (MRI) to assess in vivo cardiac
      metabolism and function in the 15-week-old spontaneously hypertensive rat (SHR)
      heart. At this time point, the SHR displays hypertension and concentric
      hypertrophy. One of the cellular adaptations to hypertrophy is a reduction in
      beta-oxidation, and it has previously been shown that in response to hypertrophy
      the SHR heart switches to a glycolytic/glucose-oxidative phenotype. METHODS AND
      RESULTS: Cine-MRI (magnetic resonance imaging) was used to assess cardiac
      function and degree of cardiac hypertrophy. Wistar rats were used as controls.
      SHRs displayed functional changes in stroke volume, heart rate, and late peak
      diastolic filling alongside significant hypertrophy (a 56% increase in left
      ventricular mass). Using hyperpolarized [1-(13)C] and [2-(13)C]pyruvate, an 85%
      increase in (13)C label flux through pyruvate dehydrogenase (PDH) was seen in the
      SHR heart and (13)C label incorporation into citrate, acetylcarnitine, and
      glutamate pools was elevated in proportion to the increase in PDH flux. These
      findings were confirmed using biochemical analysis of PDH activity and protein
      expression of PDH regulatory enzymes. CONCLUSIONS: Functional and structural
      alterations in the SHR heart are consistent with the hypertrophied phenotype. Our
      in vivo work indicates a preference for glucose metabolism in the SHR heart, a
      move away from predominantly fatty acid oxidative metabolism. Interestingly,
      (13)C label flux into lactate was unchanged, indicating no switch to an anaerobic
      glycolytic phenotype, but rather an increased reliance on glucose oxidation in
      the SHR heart.

PMID- 22593202
TI  - Atherosclerosis: what are we looking for?

PMID- 22593203
TI  - When inner ear stem cell therapy becomes a reality.

PMID- 22593204
TI  - Auditory-filter characteristics for listeners with real and simulated hearing
      impairment.
AB  - Functional simulation of sensorineural hearing impairment is an important
      research tool that can elucidate the nature of hearing impairments and suggest or
      eliminate compensatory signal-processing schemes. The objective of the current
      study was to evaluate the capability of an audibility-based functional simulation
      of hearing loss to reproduce the auditory-filter characteristics of listeners
      with sensorineural hearing loss. The hearing-loss simulation used either
      threshold-elevating noise alone or a combination of threshold-elevating noise and
      multiband expansion to reproduce the audibility-based characteristics of the loss
      (including detection thresholds, dynamic range, and loudness recruitment). The
      hearing losses of 10 listeners with bilateral, mild-to-severe hearing loss were
      simulated in 10 corresponding groups of 3 age-matched normal-hearing listeners.
      Frequency selectivity was measured using a notched-noise masking paradigm at five
      probe frequencies in the range of 250 to 4000 Hz with a fixed probe level of
      either 70 dB SPL or 8 dB SL (whichever was greater) and probe duration of 200 ms.
      The hearing-loss simulation reproduced the absolute thresholds of individual
      hearing-impaired listeners with an average root-mean-squared (RMS) difference of
      2.2 dB and the notched-noise masked thresholds with an RMS difference of 5.6 dB.
      A rounded-exponential model of the notched-noise data was used to estimate
      equivalent rectangular bandwidths and slopes of the auditory filters. For some
      subjects and probe frequencies, the simulations were accurate in reproducing the
      auditory-filter characteristics of the hearing-impaired listeners. In other
      cases, however, the simulations underestimated the magnitude of the auditory
      bandwidths for the hearing-impaired listeners, which suggests the possibility of
      suprathreshold deficits.

PMID- 22593205
TI  - Rab GTPase regulation of retromer-mediated cargo export during endosome
      maturation.
AB  - The retromer complex, composed of sorting nexin subunits and a Vps26/Vps29/Vps35
      trimer, mediates sorting of retrograde cargo from the endosome to the trans-Golgi
      network. The retromer trimer subcomplex is an effector of Rab7 (Ypt7 in yeast).
      Whereas endosome targeting of human retromer has been shown to require Rab7-GTP,
      targeting of yeast retromer to the endosome is independent of Ypt7-GTP and
      requires the Vps5 and Vps17 retromer sorting nexin subunits. An evolutionarily
      conserved amino acid segment within Vps35 is required for Ypt7/Rab7 recognition
      in vivo by both yeast and human retromer, establishing that Rab recognition is a
      conserved feature of this subunit. Recognition of Ypt7 by retromer is required
      for its function in retrograde sorting, and in yeast cells lacking the guanine
      nucleotide exchange factor for Ypt7, retrograde cargo accumulates in endosomes
      that are decorated with retromer, revealing an additional role for Rab
      recognition at the cargo export stage of the retromer functional cycle. In
      addition, yeast retromer trimer antagonizes Ypt7-regulated organelle tethering
      and fusion of endosomes/vacuoles via recognition of Ypt7. Thus retromer has dual
      roles in retrograde cargo export and in controlling the fusion dynamics of the
      late endovacuolar system.

PMID- 22593206
TI  - The Msb3/Gyp3 GAP controls the activity of the Rab GTPases Vps21 and Ypt7 at
      endosomes and vacuoles.
AB  - Fusion of organelles in the endomembrane system depends on Rab GTPases that
      interact with tethering factors before lipid bilayer mixing. In yeast, the Rab5
      GTPase Vps21 controls fusion and membrane dynamics between early and late
      endosomes. Here we identify Msb3/Gyp3 as a specific Vps21 GTPase-activating
      protein (GAP). Loss of Msb3 results in an accumulation of Vps21 and one of its
      effectors Vps8, a subunit of the CORVET complex, at the vacuole membrane in vivo.
      In agreement, Msb3 forms a specific transition complex with Vps21, has the
      highest activity of all recombinant GAPs for Vps21 in vitro, and is found at
      vacuoles despite its predominant localization to bud tips and bud necks at the
      plasma membrane. Surprisingly, Msb3 also inhibits vacuole fusion, which can be
      rescued by the Ypt7 GDP-GTP exchange factor (GEF), the Mon1-Ccz1 complex.
      Consistently, msb3 vacuoles fuse more efficiently than wild-type vacuoles in
      vitro, suggesting that GAP can also act on Ypt7. Our data indicate that GAPs such
      as Msb3 can act on multiple substrates in vivo at both ends of a trafficking
      pathway. This ensures specificity of the subsequent GEF-mediated activation of
      the Rab that initiates the next transport event.

PMID- 22593207
TI  - Numbl inhibits glioma cell migration and invasion by suppressing TRAF5-mediated
      NF-kappaB activation.
AB  - The Notch signaling regulator Numblike (Numbl) is expressed in the brain, but
      little is known regarding its role in the pathophysiology of glial cells. In this
      paper, we report that Numbl expression was down-regulated in high-grade human
      glioma tissue samples and glioblastoma cell lines. To investigate the role of
      Numbl in glioma migration and invasion, we generated human glioma cell lines in
      which Numbl was either overexpressed or depleted. Overexpression of Numbl
      suppressed, while elimination of Numbl promoted, the migration and invasion of
      glioma cells. Numbl inhibited glioma migration and invasion by dampening NF
      kappaB activity. Furthermore, Numbl interacted directly with tumor necrosis
      factor receptor-associated factor 5 (TRAF5), which signals upstream and is
      required for the activation of NF-kappaB, and committed it to proteasomal
      degradation by promoting K48-linked polyubiquitination of TRAF5. In conclusion,
      our data suggest that Numbl negative regulates glioma cell migration and invasion
      by abrogating TRAF5-induced activation of NF-kappaB.

PMID- 22593208
TI  - The inositol 5-phosphatase SHIP2 is an effector of RhoA and is involved in cell
      polarity and migration.
AB  - Cell migration is essential for various physiological and pathological processes.
      Polarization in motile cells requires the coordination of several key signaling
      molecules, including RhoA small GTPases and phosphoinositides. Although RhoA
      participates in a front-rear polarization in migrating cells, little is known
      about the functional interaction between RhoA and lipid turnover. We find here
      that src-homology 2-containing inositol-5-phosphatase 2 (SHIP2) interacts with
      RhoA in a GTP-dependent manner. The association between SHIP2 and RhoA is
      observed in spreading and migrating U251 glioma cells. The depletion of SHIP2
      attenuates cell polarization and migration, which is rescued by wild-type SHIP2
      but not by a mutant defective in RhoA binding. In addition, the depletion of
      SHIP2 impairs the proper localization of phosphatidylinositol 3,4,5
      trisphosphate, which is not restored by a mutant defective in RhoA binding. These
      results suggest that RhoA associates with SHIP2 to regulate cell polarization and
      migration.

PMID- 22593209
TI  - RTEL1 contributes to DNA replication and repair and telomere maintenance.
AB  - Telomere maintenance and DNA repair are important processes that protect the
      genome against instability. mRtel1, an essential helicase, is a dominant factor
      setting telomere length in mice. In addition, mRtel1 is involved in DNA double
      strand break repair. The role of mRtel1 in telomere maintenance and genome
      stability is poorly understood. Therefore we used mRtel1-deficient mouse
      embryonic stem cells to examine the function of mRtel1 in replication, DNA
      repair, recombination, and telomere maintenance. mRtel1-deficient mouse embryonic
      stem cells showed sensitivity to a range of DNA-damaging agents, highlighting its
      role in replication and genome maintenance. Deletion of mRtel1 increased the
      frequency of sister chromatid exchange events and suppressed gene replacement,
      demonstrating the involvement of the protein in homologous recombination. mRtel1
      localized transiently at telomeres and is needed for efficient telomere
      replication. Of interest, in the absence of mRtel1, telomeres in embryonic stem
      cells appeared relatively stable in length, suggesting that mRtel1 is required to
      allow extension by telomerase. We propose that mRtel1 is a key protein for DNA
      replication, recombination, and repair and efficient elongation of telomeres by
      telomerase.

PMID- 22593210
TI  - Tension-dependent nucleosome remodeling at the pericentromere in yeast.
AB  - Nucleosome positioning is important for the structural integrity of chromosomes.
      During metaphase the mitotic spindle exerts physical force on pericentromeric
      chromatin. The cell must adjust the pericentromeric chromatin to accommodate the
      changing tension resulting from microtubule dynamics to maintain a stable
      metaphase spindle. Here we examine the effects of spindle-based tension on
      nucleosome dynamics by measuring the histone turnover of the chromosome arm and
      the pericentromere during metaphase in the budding yeast Saccharomyces
      cerevisiae. We find that both histones H2B and H4 exhibit greater turnover in the
      pericentromere during metaphase. Loss of spindle-based tension by treatment with
      the microtubule-depolymerizing drug nocodazole or compromising kinetochore
      function results in reduced histone turnover in the pericentromere.
      Pericentromeric histone dynamics are influenced by the chromatin-remodeling
      activities of STH1/NPS1 and ISW2. Sth1p is the ATPase component of the Remodels
      the Structure of Chromatin (RSC) complex, and Isw2p is an ATP-dependent DNA
      translocase member of the Imitation Switch (ISWI) subfamily of chromatin
      remodeling factors. The balance between displacement and insertion of
      pericentromeric histones provides a mechanism to accommodate spindle-based
      tension while maintaining proper chromatin packaging during mitosis.

PMID- 22593211
TI  - R-Ras controls axon branching through afadin in cortical neurons.
AB  - Regulation of axon growth, guidance, and branching is essential for constructing
      a correct neuronal network. R-Ras, a Ras-family small GTPase, has essential roles
      in axon formation and guidance. During axon formation, R-Ras activates a series
      of phosphatidylinositol 3-kinase signaling, inducing activation of a microtubule
      assembly promoter-collapsin response mediator protein-2. However, signaling
      molecules linking R-Ras to actin cytoskeleton-regulating axonal morphology remain
      obscure. Here we identify afadin, an actin-binding protein harboring Ras
      association (RA) domains, as an effector of R-Ras inducing axon branching through
      F-actin reorganization. We observe endogenous interaction of afadin with R-Ras in
      cortical neurons during the stage of axonal development. Ectopic expression of
      afadin increases axon branch number, and the RA domains and the carboxyl-terminal
      F-actin binding domain are required for this action. RNA interference knockdown
      experiments reveal that knockdown of endogenous afadin suppressed both basal and
      R-Ras-mediated axon branching in cultured cortical neurons. Subcellular
      localization analysis shows that active R-Ras-induced translocation of afadin and
      its RA domains is responsible for afadin localizing to the membrane and inducing
      neurite development in Neuro2a cells. Overall, our findings demonstrate a novel
      signaling pathway downstream of R-Ras that controls axon branching.

PMID- 22593212
TI  - Endoglin regulates PI3-kinase/Akt trafficking and signaling to alter endothelial
      capillary stability during angiogenesis.
AB  - Endoglin (CD105) is an endothelial-specific transforming growth factor beta (TGF
      beta) coreceptor essential for angiogenesis and vascular homeostasis. Although
      endoglin dysfunction contributes to numerous vascular conditions, the mechanism
      of endoglin action remains poorly understood. Here we report a novel mechanism in
      which endoglin and Galpha-interacting protein C-terminus-interacting protein
      (GIPC)-mediated trafficking of phosphatidylinositol 3-kinase (PI3K) regulates
      endothelial signaling and function. We demonstrate that endoglin interacts with
      the PI3K subunits p110alpha and p85 via GIPC to recruit and activate PI3K and Akt
      at the cell membrane. Opposing ligand-induced effects are observed in which TGF
      beta1 attenuates, whereas bone morphogenetic protein-9 enhances, endoglin/GIPC
      mediated membrane scaffolding of PI3K and Akt to alter endothelial capillary tube
      stability in vitro. Moreover, we employ the first transgenic zebrafish model for
      endoglin to demonstrate that GIPC is a critical component of endoglin function
      during developmental angiogenesis in vivo. These studies define a novel non-Smad
      function for endoglin and GIPC in regulating endothelial cell function during
      angiogenesis.

PMID- 22593214
TI  - Microtubules regulate GEF-H1 in response to extracellular matrix stiffness.
AB  - Breast epithelial cells sense the stiffness of the extracellular matrix through
      Rho-mediated contractility. In turn, matrix stiffness regulates RhoA activity.
      However, the upstream signaling mechanisms are poorly defined. Here we
      demonstrate that the Rho exchange factor GEF-H1 mediates RhoA activation in
      response to extracellular matrix stiffness. We demonstrate the novel finding that
      microtubule stability is diminished by a stiff three-dimensional (3D)
      extracellular matrix, which leads to the activation of GEF-H1. Surprisingly,
      activation of the mitogen-activated protein kinase kinase/extracellular signal
      regulated kinase pathway did not contribute to stiffness-induced GEF-H1
      activation. Loss of GEF-H1 decreases cell contraction of and invasion through 3D
      matrices. These data support a model in which matrix stiffness regulates RhoA
      through microtubule destabilization and the subsequent release and activation of
      GEF-H1.

PMID- 22593215
TI  - Disease surveillance system: a mandatory conduit for effective control of
      infectious diseases in Pakistan.
AB  - In Pakistan, absence of a nationwide surveillance mechanism and strategy is the
      main reason for the failure in effectively controlling communicable diseases. The
      seasonal outbreaks of various infectious diseases every year call for an
      integrated surveillance system on a national level for planning effective
      preventive strategies. Opportunity to adopt a tested and tried model exists at
      this time in terms of the "Disease Early Warning System" set up by World Health
      Organization in conflict-affected districts. Replicating this system in other
      districts is both practical and feasible as technical support is readily
      available through the World Health Organization. Such a system once put in place
      has potential to not only decrease morbidity and mortality through early
      detection and prompt control of outbreaks but also to facilitate effective
      financial, human resource, and materials management at the district level. This
      would be a step toward a more responsive health system at the local level.

PMID- 22593213
TI  - Acetylation of the SUN protein Mps3 by Eco1 regulates its function in nuclear
      organization.
AB  - The Saccharomyces cerevisiae SUN-domain protein Mps3 is required for duplication
      of the yeast centrosome-equivalent organelle, the spindle pole body (SPB), and it
      is involved in multiple aspects of nuclear organization, including telomere
      tethering and gene silencing at the nuclear membrane, establishment of sister
      chromatid cohesion, and repair of certain types of persistent DNA double-stranded
      breaks. How these diverse SUN protein functions are regulated is unknown. Here we
      show that the Mps3 N-terminus is a substrate for the acetyltransferase Eco1/Ctf7
      in vitro and in vivo and map the sites of acetylation to three lysine residues
      adjacent to the Mps3 transmembrane domain. Mutation of these residues shows that
      acetylation is not essential for growth, SPB duplication, or distribution in the
      nuclear membrane. However, analysis of nonacetylatable mps3 mutants shows that
      this modification is required for accurate sister chromatid cohesion and for
      chromosome recruitment to the nuclear membrane. Acetylation of Mps3 by Eco1 is
      one of the few regulatory mechanisms known to control nuclear organization.

PMID- 22593216
TI  - Reliability and validity of a physical activity scale among urban pregnant women
      in eastern China.
AB  - OBJECTIVES: This study aimed to determine the reliability and validity of the
      physical activity scale adapted from a Danish scale for assessing physical
      activity among urban pregnant women in eastern China. DESIGN: Participants
      recruited in an urban setting of eastern China were asked to complete the
      physical activity scale, the activity diary, and to wear a pedometer for the same
      4 days, followed by repeating the activity scale for another 4 days within 2
      weeks. RESULTS: A total of 109 pregnant women completed data recording. Good
      reliability of the physical activity scale was observed (intraclass correlation
      coefficient = .87). There was also a good comparability between the activity
      scale and the activity diary (Spearman's r = .75 for total energy expenditure).
      The agreement between the scale and pedometer reading was acceptable (Spearman's
      r = .45). CONCLUSIONS: The adapted physical activity scale is a reliable and
      reasonably accurate instrument for estimating physical activity among urban
      pregnant women in eastern China.

PMID- 22593217
TI  - Reliability and validity of the Malay International Physical Activity
      Questionnaire (IPAQ-M) among a Malay population in Malaysia.
AB  - The International Physical Activity Questionnaire (IPAQ) was developed to assess
      the physical activity patterns in populations. The authors aim to examine the
      reliability and validity of the Malay version of IPAQ (IPAQ-M). The IPAQ-M was
      self-administered twice at a 1-week interval to assess its test-retest
      reliability. Criterion validity was assessed between the IPAQ-M and a 7-day
      physical activity log (PA-Log). A total of 81 Malay adults participated in the
      study. Intraclass correlation coefficients (ICC), kappa (kappa), correlation
      coefficients (rho), and Bland-Altman plot were used for data analyses. The ICC
      scores revealed moderate to good correlations (ICC = 0.54-0.92; P < .001) on
      items categorized by intensities and domains and a kappa of 0.73 for total
      activity. Validity results from the PA-Log were statistically significant (P <
      .001) across intensities and domains (rho = 0.67-0.98). The IPAQ-M demonstrated
      good reliability and validity for the evaluation of physical activity among this
      Malay population. 

PMID- 22593218
TI  - Risk factors associated with nephrolithiasis: a case-control study in China.
AB  - Nephrolithiasis is a multifactorial disease. The authors conducted a case-control
      study in China to explore its associated risk factors. A total of 725
      nephrolithiasis patients and 553 controls were asked to complete a questionnaire
      that asked for information about psychological, behavioral, and dietary factors
      along with a physical and blood biochemical examination. For men, higher
      education was negatively associated with nephrolithiasis (odds ratio [OR] = 0.6;
      95% confidence interval [CI] = 0.4-1.0), whereas hypso-waist-to-hip ratio (hypso
      WHR), defined as WHRs >0.9 for men and >0.8 for women (OR = 2.2; 95% CI = 1.4
      3.4); overexercise (OR = 2.1; 95% CI = 1.3-3.5); and having experienced negative
      life events (OR = 2.2; 95% CI = 1.2-4.1) were positively associated with
      nephrolithiasis. For women, higher fluid intake was negatively associated with
      nephrolithiasis (OR = 0.6; 95% CI = 0.3-0.9), and abnormal status of blood
      pressure (BP) and blood lipids was positively associated with nephrolithiasis.
      Varied factors were related to differences in nephrolithiasis occurrence between
      genders. Besides taking enough fluids, maintaining a normal metabolic status,
      avoiding overexercise, and reducing BP might be beneficial in preventing
      nephrolithiasis. 

PMID- 22593219
TI  - Trends and barriers to HIV testing among tuberculosis patients in Prey Kabas
      operational district, Takeo province, Cambodia.
AB  - Data for this study were obtained from 2375 tuberculosis (TB) patients registered
      during 2007-2009 and 43 health providers to examine the trend of TB patient
      referral for HIV (human immunodeficiency virus) testing and to investigate
      provider-associated barriers to the referral in Prey Kabas operational district,
      Takeo province, Cambodia. Referral rate for HIV testing was 4.4% (30/684) in
      2007, 15.4% (116/751) in 2008, and 30.1% (283/940) in 2009, with a significant
      upward trend over the period of time (P = .009). The main barriers perceived by
      health providers were poor knowledge about TB/HIV, lack of communication skills,
      absence of any target plan for TB patient referral for HIV testing, and fear
      associated with informing positive test results to the TB patients and the
      associated stigma. Strategies to raise awareness about HIV/AIDS/TB among TB
      patients and their providers may improve the current state of low referral and
      its barriers in Cambodia. 

PMID- 22593220
TI  - Physical activity and obesity research in the Asia-Pacific: a review.
AB  - Obesity is a global health concern and has a great impact on countries in the
      Asia-Pacific region. Physical inactivity is a major risk factor for obesity, but
      physical activity levels are declining in much of this region. Increasing
      physical activity is a priority in many countries. Considerable research has been
      conducted on physical activity related to obesity in Western countries, but
      populations in the Asia-Pacific region differ in physical, psychological, social,
      and cultural ways that warrant local and regional research. The authors reviewed
      research conducted in the Asia-Pacific region that examined either the impact of
      physical activity interventions on obesity-related outcomes or the effect of
      behavior-change interventions on physical activity participation. The number of
      studies found was limited, and their samples and methods varied too much to draw
      conclusions. The authors recommend further research in the Asia-Pacific region
      using systematic protocols to permit sound conclusions to be drawn and promote
      informed action at local levels.

PMID- 22593221
TI  - Oral hygiene risk indicators among 6- to 9-year-old Taiwanese aboriginal
      children.
AB  - This study investigated the dental health status, dietary habits, oral hygiene
      levels, and caretaker risk indicators among Taiwanese children. This cross
      sectional purposive sampling study included 256 aboriginal children, 6 to 9 years
      old, living in remote regions in southern Taiwan. Participants received dental
      examinations, and questionnaires were completed by caretakers. Data were analyzed
      using the chi(2) test, t test, and multiple logistic regressions. The deft (sum
      of decayed, extracted, and filled primary teeth) and defs (sum of the decayed,
      extracted, and filled primary dentition surfaces) indices were affected by the
      frequencies of drinking sweetened beverages (P = .0006) and daily toothbrushing
      (P = .0032). Caretakers' toothbrushing frequency was a significant predictor of
      children's oral hygiene status (P < .0001). The odds ratio for children of
      caretakers with betel quid chewing habits having poor oral hygiene was 2.04 (P =
      .0184). Oral hygiene among aboriginal children in this study was inadequate.
      Caretakers' toothbrushing frequency and betel quid habit were significant
      predictors of poor children's oral hygiene. 

PMID- 22593222
TI  - A systematic review of school-based interventions to prevent risk factors
      associated with noncommunicable diseases.
AB  - Noncommunicable diseases (NCDs) are emerging as an important public health
      problem in developing countries. The risk factors for NCDs are initiated during
      childhood and adolescence. The aim of this review was to assess the effectiveness
      of school-based interventions for prevention of NCD risk factors (physical
      inactivity, diet, and tobacco consumption), and identify processes that affect
      the main outcome. The retrieved studies from 2001 to 2010 were analyzed for their
      methodological quality (using standard guidelines), settings, intervention
      components, and main outcomes. The literature search identified 37 studies. The
      proportion of studies showing a positive result was 83% (10/12) among those that
      involved family, 87%(7/8) that involved both community and family, and 76%
      (13/17) that involved school only. Overall, 80% of the studies reported at least
      some evidence of a positive intervention effect. The current literature search
      supports the effectiveness of school-based interventions for prevention of risk
      factors associated with NCDs.

PMID- 22593223
TI  - Ultradeep sequencing analysis of population dynamics of virus escape mutants in
      RNAi-mediated resistant plants.
AB  - Plant artificial micro-RNAs (amiRs) have been engineered to target viral genomes
      and induce their degradation. However, the exceptional evolutionary plasticity of
      RNA viruses threatens the durability of the resistance conferred by these amiRs.
      It has recently been shown that viral populations not experiencing strong
      selective pressure from an antiviral amiR may already contain enough genetic
      variability in the target sequence to escape plant resistance in an almost
      deterministic manner. Furthermore, it has also been shown that viral populations
      exposed to subinhibitory concentrations of the antiviral amiR speed up this
      process. In this article, we have characterized the molecular evolutionary
      dynamics of an amiR target sequence in a viral genome under both conditions. The
      use of Illumina ultradeep sequencing has allowed us to identify virus sequence
      variants at frequencies as low as 2 * 10(-6) and to track their variation in time
      before and after the viral population was able of successfully infecting plants
      fully resistant to the ancestral virus. We found that every site in the amiR
      target sequence of the viral genome presented variation and that the variant that
      eventually broke resistance was sampled among the many coexisting ones. In this
      system, viral evolution in fully susceptible plants results from an equilibrium
      between mutation and genetic drift, whereas evolution in partially resistant
      plants originates from more complex dynamics involving mutation, selection, and
      drift.

PMID- 22593224
TI  - Unidirectional evolutionary transitions in fungal mating systems and the role of
      transposable elements.
AB  - In the fungal kingdom, the evolution of mating systems is highly dynamic, varying
      even among closely related species. Rearrangements in the mating-type (mat)
      locus, which contains the major regulators of sexual development, are expected to
      underlie the transitions between self-sterility (heterothallism) and self
      fertility (homothallism). However, both the genetic mechanisms and the direction
      of evolutionary transitions in fungal mating systems are under debate. Here, we
      present new sequences of the mat locus of four homothallic and one heterothallic
      species of the model genus Neurospora (Ascomycota). By examining the patterns of
      synteny among these sequences and previously published data, we show that the
      locus is conserved among heterothallic species belonging to distinct phylogenetic
      clades, while different gene arrangements characterize the four homothallic
      species. These results allowed us to ascertain a heterothallic ancestor for the
      genus, confirming the prediction of the dead-end theory on unidirectional
      transitions toward selfing. We show that at least four shifts from heterothallism
      to homothallism have occurred in Neurospora, three of which involve the
      acquisition of sequences of both mating types into the same haploid genome. We
      present evidence for two genetic mechanisms allowing these shifts: translocation
      and unequal crossover. Finally, we identified two novel retrotransposons and
      suggest that these have played a major role in mating-system transitions, by
      facilitating multiple rearrangements of the mat locus.

PMID- 22593225
TI  - Loss of two introns from the Magnolia tripetala mitochondrial cox2 gene
      implicates horizontal gene transfer and gene conversion as a novel mechanism of
      intron loss.
AB  - Intron loss is often thought to occur through retroprocessing, which is the
      reverse transcription and genomic integration of a spliced transcript. In plant
      mitochondria, several unambiguous examples of retroprocessing are supported by
      the parallel loss of an intron and numerous adjacent RNA edit sites, but in most
      cases, the evidence for intron loss via retroprocessing is weak or lacking
      entirely. To evaluate mechanisms of intron loss, we designed a polymerase chain
      reaction (PCR)-based assay to detect recent intron losses from the mitochondrial
      cox2 gene within genus Magnolia, which was previously suggested to have
      variability in cox2 intron content. Our assay showed that all 22 examined species
      have a cox2 gene with two introns. However, one species, Magnolia tripetala,
      contains an additional cox2 gene that lacks both introns. Quantitative PCR showed
      that both M. tripetala cox2 genes are present in the mitochondrial genome.
      Although the intronless gene has lost several ancestral RNA edit sites, their
      distribution is inconsistent with retroprocessing models. Instead, phylogenetic
      and gene conversion analyses indicate that the intronless gene was horizontally
      acquired from a eudicot and then underwent gene conversion with the native intron
      containing gene. The models are presented to summarize the roles of horizontal
      gene transfer and gene conversion as a novel mechanism of intron loss.

PMID- 22593226
TI  - Recent retrotransposon insertions are methylated and phylogenetically clustered
      in japonica rice (Oryza sativa spp. japonica).
AB  - In plants, the genome of the host responds to the amplification of transposable
      elements (TEs) with DNA methylation. However, neither the factors involved in TE
      methylation nor the dynamics of the host-TE interaction are well resolved. Here,
      we identify 5,522 long terminal repeat retrotransposons (LTR-RT) in the genome of
      Oryza sativa ssp. japonica and then assess methylation for individual elements.
      Our analyses uncover three strong trends: long LTR-RTs are more highly
      methylated, the insertion times of LTR-RTs are negatively correlated with
      methylation, and young LTR-RTs tend to be closer to genes than older insertions.
      Additionally, a phylogenetic examination of the gypsy-like LTR-RT superfamily
      revealed that methylation is phylogenetically correlated. Given these
      observations, we present a model suggesting that the phylogenetic correlation
      among related LTR-RTs is a primary mechanism driving methylation. In this model,
      bursts of transposition produce new elements with high sequence similarity. The
      host machinery identifies proliferating elements as well as closely related LTR
      RTs through cross-homology. In addition, our data are consistent with previous
      hypotheses that methylated LTR-RT elements are removed preferentially from
      regions near genes, explaining some of the observed age distribution.

PMID- 22593227
TI  - A model for the evolution of the mammalian t-cell receptor alpha/delta and MU
      loci based on evidence from the duckbill Platypus.
AB  - The specific recognition of antigen by T cells is critical to the generation of
      adaptive immune responses in vertebrates. T cells recognize antigen using a
      somatically diversified T-cell receptor (TCR). All jawed vertebrates use four TCR
      chains called alpha, beta, gamma, and delta, which are expressed as either a
      alphabeta or gammadelta heterodimer. Nonplacental mammals (monotremes and
      marsupials) are unusual in that their genomes encode a fifth TCR chain, called
      TCRu, whose function is not known but is also somatically diversified like the
      conventional chains. The origins of TCRu are also unclear, although it appears
      distantly related to TCRdelta. Recent analysis of avian and amphibian genomes has
      provided insight into a model for understanding the evolution of the TCRdelta
      genes in tetrapods that was not evident from humans, mice, or other commonly
      studied placental (eutherian) mammals. An analysis of the genes encoding the
      TCRdelta chains in the duckbill platypus revealed the presence of a highly
      divergent variable (V) gene, indistinguishable from immunoglobulin heavy (IgH)
      chain V genes (VH) and related to V genes used in TCRu. They are expressed as
      part of TCRdelta repertoire (VHdelta) and similar to what has been found in frogs
      and birds. This, however, is the first time a VHdelta has been found in a mammal
      and provides a critical link in reconstructing the evolutionary history of TCRu.
      The current structure of TCRdelta and TCRu genes in tetrapods suggests ancient
      and possibly recurring translocations of gene segments between the IgH and
      TCRdelta genes, as well as translocations of TCRdelta genes out of the
      TCRalpha/delta locus early in mammals, creating the TCRu locus.

PMID- 22593228
TI  - New use for an old drug: inhibiting ABCG2 with sorafenib.
AB  - Human ABCG2, a member of the ATP-binding cassette transporter superfamily,
      represents a promising target for sensitizing MDR in cancer chemotherapy.
      Although lots of ABCG2 inhibitors were identified, none of them has been tested
      clinically, maybe because of several problems such as toxicity or safety and
      pharmacokinetic uncertainty of compounds with novel chemical structures. One
      efficient solution is to rediscover new uses for existing drugs with known
      pharmacokinetics and safety profiles. Here, we found the new use for sorafenib,
      which has a dual-mode action by inducing ABCG2 degradation in lysosome in
      addition to inhibiting its function. Previously, we reported some novel dual
      acting ABCG2 inhibitors that showed closer similarity to degradation-induced
      mechanism of action. On the basis of these ABCG2 inhibitors with diverse chemical
      structures, we developed a pharmacophore model for identifying the critical
      pharmacophore features necessary for dual-acting ABCG2 inhibitors. Sorafenib
      forms impressive alignment with the pharmacophore hypothesis, supporting the
      argument that sorafenib is a potential ABCG2 inhibitor. This is the first article
      that sorafenib may be a good candidate for chemosensitizing agent targeting ABCG2
      mediated MDR. This study may facilitate the rediscovery of new functions of
      structurally diverse old drugs and provide a more effective and safe way of
      sensitizing MDR in cancer chemotherapy.

PMID- 22593229
TI  - Incorporating salivary biomarkers into nursing research: an overview and review
      of best practices.
AB  - Analytes and biomarkers present in saliva may provide insight into individual
      differences in environmental chemical exposures, variation in reproductive
      hormones, therapeutic and illegal substance use, changes in stress-related
      physiology, and the immunologic footprints of infectious disease. The wealth of
      information provided by salivary analytes has the potential to enrich
      biobehavioral nursing research by enabling researchers to measure these
      individual differences in the clinic as well as in patients' and participants'
      everyday social worlds. In this article, the authors provide a roadmap for
      researchers new to this area who would like to learn more about integrating
      salivary biospecimens into the next generation of health research. In addition,
      the authors highlight best practices and strategies to avoid common pitfalls for
      researchers already engaged in this field.

PMID- 22593230
TI  - A comparison of the effects of fixed- and rotating-shift schedules on nursing
      staff attention levels: a randomized trial.
AB  - PURPOSE: Sleep deficit affects neurobehavioral functioning, reduces attention and
      cognitive function, and negatively impacts occupational safety. This study
      investigated selective attention levels of nursing staff on different shifts.
      METHODS: Using a prospective, randomized parallel group study, selective
      attention was measured using the d2 test in 62 nursing staff in a medical center
      in Taiwan. FINDINGS: There were significant differences in selective attention
      indicators (E%) between the fixed-day-shift group (control group) and rotating
      shift group (experimental group): The percentage of errors (E%) for night-shift
      workers in the rotating-shift group was higher than that of fixed-day-shift
      workers, while the total number of items scanned minus error (TN - E) and
      concentration performance (CP) scores were higher for fixed-day-shift workers.
      Within the experimental group, the error rate on night shift was 0.44 times more
      than that on day shift and .62 times more than on evening shift; the TN-E on
      night shift was 38.99 items less than that on day shift, and the CP was 27.68
      items less on night shift than on day shift; indicating that staff on the night
      shift demonstrated poorer speed and accuracy on the overall test than did the
      staff on day shifts. CONCLUSIONS: Inadequate sleep and a state of somnolence
      adversely affected the attention and operation speed of work among night-shift
      workers. More than 2 days off is suggested when shifting from the night shift to
      other shifts to provide adequate time for circadian rhythms to adjust.

PMID- 22593231
TI  - Bright light therapy to promote sleep in mothers of low-birth-weight infants: a
      pilot study.
AB  - Having a low-birth-weight (LBW) infant in a neonatal intensive care unit (NICU)
      can intensify a mother's sleep disturbances due to both stress and the dim
      lighting in the ICU setting, which desynchronizes circadian rhythms. The purpose
      of this pilot study was to examine the effectiveness of a 3-week bright light
      therapy intervention on sleep and health outcomes of mothers with LBW infants in
      the NICU. Controlled stratified randomization was used to assign 30 mothers to a
      treatment or control group. Data were collected at pretreatment (second week
      postpartum) and after the 3-week intervention. Sleep data were assessed by wrist
      actigraph (total sleep time [TST], circadian activity rhythms [CARs]) and the
      General Sleep Disturbance scale. Other outcome variables were measured by the
      Lee's Fatigue scale, Edinburgh Postpartum Depression scale, and the Medical
      Outcomes Short Form 36, version 2. Mothers averaged 26.6 (SD = 6.3) years of age,
      and the majority were Black (73%). The mean gestational age for the infants was
      27.7 (SD = 2.0) weeks. Small to large effect sizes were found when comparing the
      pre- to posttreatment differences between groups. Although none of the
      differences were statistically significant in this small sample, for mothers in
      the treatment group nocturnal TST (d = .33), CAR (d = 1.06), morning fatigue (d =
      .22), depressive symptoms (d = .40), physical health-related quality of life (d =
      .33), and mental health-related quality of life (d = .60) all improved compared
      to the control group. Bright light therapy is feasible for mothers with infants
      in an NICU. Clinically significant improvements have been evidenced; a larger
      scale trial of effectiveness is needed.

PMID- 22593232
TI  - Tumor necrosis factor-alpha gene polymorphisms in FMF and their association with
      amyloidosis.
AB  - Familial Mediterranean fever (FMF) is an autosomal recessive disorder
      characterized by periodic provocative attacks of fever with peritonitis,
      pleuritis, arthritis, or eriseplemya. Tumor necrosis factor-alpha (TNF-alpha)
      plays an important role in the regulation of the immune response as a part of the
      cytokine network, including activation of macrophages and apoptosis. We
      investigated the possible association of TNF-alpha promoter -1031T/C and -308G/A
      polymorphisms in 86 FMF patients carrying M694 V homozygous mutation and 100
      matched healthy controls both from Iranian Azeri Turks. Our data showed that
      patients with TNF-alpha -308 GG are more susceptible to the development of
      amyloidosis and arthritis (P value <.05). These data also showed that the
      frequency of TNF-alpha -308 A allele is considerably low among patients with
      amyloidosis, and it may have protective role among them (odds ratio [OR] = 0.083,
      chi(2) = 5.46, P value = .003). Further evaluation of this polymorphism may be
      important and need further studies.

PMID- 22593233
TI  - Regulatory forum opinon piece: raw data in pathology--always a conundrum, often a
      controversy.

PMID- 22593235
TI  - Characterization and toxicological evaluation of leachate from closed sanitary
      landfill.
AB  - Landfilling is a major option in waste management hierarchy in developing
      nations. It generates leachate, which has the potential of polluting
      watercourses. This study analysed the physico-chemical components of leachate
      from a closed sanitary landfill in Malaysia, in relation to evaluating the
      toxicological impact on fish species namely Pangasius sutchi S., 1878 and Clarias
      batrachus L., 1758. The leachate samples were taken from Air Hitam Sanitary
      Landfill (AHSL) and the static method of acute toxicity testing was experimented
      on both fish species at different leachate concentrations. Each fish had an
      average of 1.3 +/- 0.2 g wet weight and length of 5.0 +/- 0.1 cm. Histology of
      the fishes was examined by analysing the gills of the response (dead) group,
      using the Harris haemtoxylin and eosin (H&E) method. Finneys' Probit method was
      utilized as a statistical tool to evaluate the data from the fish test. The
      physico-chemical analysis of the leachate recorded pH 8.2 +/- 0.3, biochemical
      oxygen demand 3500 +/- 125 mg L(-1), COD 10 234 +/- 175 mg L(-1), ammonical
      nitrogen of 880 +/- 74 mg L(-1), benzene 0.22 +/- 0.1 mg L(-1) and toluene 1.2 +/
      0.4 mg L(-1). The 50% lethality concentration (LC(50)) values calculated after
      96 h exposure were 3.2% (v/v) and 5.9% (v/v) of raw leachate on P. sutchi and C.
      batrachus, respectively. The H&E staining showed denaturation of the nucleus and
      cytoplasm of the gills of the response groups. Leachate from the sanitary
      landfill was toxic to both fish species. The P. sutchi and C. batrachus may be
      used as indicator organisms for leachate pollution in water.

PMID- 22593236
TI  - A human papillomavirus (HPV) in vitro neutralization assay that recapitulates the
      in vitro process of infection provides a sensitive measure of HPV L2 infection
      inhibiting antibodies.
AB  - Papillomavirus L2-based vaccines have generally induced low-level or undetectable
      neutralizing antibodies in standard in vitro assays yet typically protect well
      against in vivo experimental challenge in animal models. Herein we document that
      mice vaccinated with an L2 vaccine comprising a fusion protein of the L2 amino
      acids 11 to 88 of human papillomavirus type 16 (HPV16), HPV18, HPV1, HPV5, and
      HPV6 were uniformly protected from cervicovaginal challenge with HPV16
      pseudovirus, but neutralizing antibodies against HPV16, -31, -33, -45, or -58
      were rarely detected in their sera using a standard in vitro neutralization
      assay. To address this discrepancy, we developed a neutralization assay based on
      an in vitro infectivity mechanism that more closely mimics the in vivo infectious
      process, specifically by spaciotemporally separating primary and secondary
      receptor engagement and correspondingly by altering the timing of exposure of the
      dominant L2 cross-neutralizing epitopes to the antibodies. With the new assay,
      titers in the 100 to 10,000 range were measured for most sera, whereas
      undetectable neutralizing activities were observed with the standard assay. In
      vitro neutralizing titers measured in the serum of mice after passive transfer of
      rabbit L2 immune serum correlated with protection from cervicovaginal challenge
      of the mice. This "L2-based" in vitro neutralization assay should prove useful in
      critically evaluating the immunogenicity of L2 vaccine candidates in preclinical
      studies and future clinical trials.

PMID- 22593237
TI  - Analysis of variola and vaccinia virus neutralization assays for smallpox
      vaccines.
AB  - Possible smallpox reemergence drives research for third-generation vaccines that
      effectively neutralize variola virus. A comparison of neutralization assays using
      different substrates, variola and vaccinia (Dryvax and modified vaccinia Ankara
      [MVA]), showed significantly different 90% neutralization titers; Dryvax
      underestimated while MVA overestimated variola neutralization. Third-generation
      vaccines may rely upon neutralization as a correlate of protection.

PMID- 22593238
TI  - Analysis of heavy-chain antibody responses and resistance to Parelaphostrongylus
      tenuis in experimentally infected alpacas.
AB  - The parasitic nematode Parelaphostrongylus tenuis is an important cause of
      neurologic disease of camelids in central and eastern North America. The aim of
      this study was to determine whether alpacas develop resistance to disease caused
      by P. tenuis in response to a previous infection or a combination of controlled
      infection and immunization. Alpacas were immunized with a homogenate of third
      stage larvae (L3) and simultaneously implanted subcutaneously with diffusion
      chambers containing 20 live L3. Sham-treated animals received adjuvant alone and
      empty chambers. The protocol was not effective in inducing resistance to oral
      challenge with 10 L3, and disease developed between 60 and 71 days following
      infection. Immediately following the onset of neurologic disease, affected
      animals were treated with a regimen of anthelmintic and anti-inflammatory drugs,
      and all recovered. One year later, a subset of alpacas from this experiment was
      challenged with 20 L3 and the results showed that prior infection induced
      resistance to disease. Primary and secondary infections induced production of
      conventional and heavy-chain IgGs that reacted with soluble antigens in L3
      homogenates but did not consistently recognize a recombinant form of a parasite
      derived aspartyl protease inhibitor. Thus, the latter antigen may not be a good
      candidate for serology-based diagnostic tests. Antibody responses to parasite
      antigens occurred in the absence of overt disease, demonstrating that P. tenuis
      infection can be subclinical in a host that has been considered to be highly
      susceptible to disease. The potential for immunoprophylaxis to be effective in
      preventing disease caused by P. tenuis was supported by evidence of resistance to
      reinfection.

PMID- 22593239
TI  - Fell Pony syndrome: characterization of developmental hematopoiesis failure and
      associated gene expression profiles.
AB  - Fell Pony syndrome (FPS) is a fatal immunodeficiency that occurs in foals of the
      Fell Pony breed. Affected foals present with severe anemia, B cell lymphopenia,
      and opportunistic infections. Our objective was to conduct a prospective study of
      potential FPS-affected Fell Pony foals to establish clinical, immunological, and
      molecular parameters at birth and in the first few weeks of life. Complete blood
      counts, peripheral blood lymphocyte phenotyping, and serum immunoglobulin
      concentrations were determined for 3 FPS-affected foals, 49 unaffected foals, and
      6 adult horses. In addition, cytology of bone marrow aspirates was performed
      sequentially in a subset of foals. At birth, the FPS-affected foals were not
      noticeably ill and had hematocrit and circulating B cell counts comparable to
      those of unaffected foals; however, over 6 weeks, values for both parameters
      steadily declined. A bone marrow aspirate from a 3-week-old FPS-affected foal
      revealed erythroid hyperplasia and concurrent erythroid and myeloid dysplasia,
      which progressed to a severe erythroid hypoplasia at 5 weeks of life.
      Immunohistochemical staining confirmed the paucity of B cells in primary and
      secondary lymphoid tissues. The mRNA expression of genes involved in B cell
      development, signaling, and maturation was investigated using qualitative and
      quantitative reverse transcriptase PCR (RT-PCR). Several genes, including CREB1,
      EP300, MYB, PAX5, and SPI1/PU.1, were sequenced from FPS-affected and unaffected
      foals. Our study presents evidence of fetal erythrocyte and B cell hematopoiesis
      with rapid postnatal development of anemia and B lymphopenia in FPS-affected
      foals. The transition between fetal/neonatal and adult-like hematopoiesis may be
      an important aspect of the pathogenesis of FPS.

PMID- 22593241
TI  - Lipid profiles and risk of breast and ovarian cancer in the Swedish AMORIS study.
AB  - BACKGROUND: Obesity is a risk factor for breast and ovarian cancer; the
      mechanisms of action are not completely understood. Perturbed lipid metabolism
      often accompanies obesity; we therefore ascertained the associations between
      lipid components and breast and ovarian cancer risk in a prospective cohort
      study. METHODS: A total of 234,494 women with baseline measurements of
      triglycerides and total cholesterol and glucose were selected from the AMORIS
      database.A total of 27,394 had measurements of high-density lipoprotein, low
      density lipoprotein, apolipoprotein (Apo) B, and A-I. Associations between
      quartiles and dichotomized values of lipid components and breast and ovarian
      cancer risk were analyzed using Cox proportional hazard models. RESULTS: We
      identified 6,105 women diagnosed with breast cancer and 808 women diagnosed with
      ovarian cancer. A weak trend was observed between triglycerides and breast cancer
      (HR, 1.01, 95% Confidence Interval, 0.94-1.09; 0.93 (0.86-1.00) 0.91 (0.84-0.99),
      second, third, and fourth quartiles; P = 0.01). No other associations between
      lipid components and risk of breast cancer or ovarian cancer showed statistical
      significance. CONCLUSIONS: A weak protective association was found between levels
      of triglycerides and risk of breast cancer. IMPACT: An analysis including
      information on tumour characteristics of ovarian cancer and breast cancer may
      provide more insight in possible links between lipid metabolism and the risk of
      these cancers.

PMID- 22593240
TI  - MAP1272c encodes an NlpC/P60 protein, an antigen detected in cattle with Johne's
      disease.
AB  - The protein encoded by MAP1272c has been shown to be an antigen of Mycobacterium
      avium subsp. paratuberculosis that contains an NlpC/P60 superfamily domain found
      in lipoproteins or integral membrane proteins. Proteins containing this domain
      have diverse enzymatic functions that include peptidases, amidases, and
      acetyltransferases. The NlpC protein was examined in comparison to over 100
      recombinant proteins and showed the strongest antigenicity when analyzed with
      sera from cattle with Johne's disease. To further localize the immunogenicity of
      NlpC, recombinant proteins representing defined regions were expressed and
      evaluated with sera from cattle with Johne's disease. The region from amino acids
      74 to 279 was shown to be the most immunogenic. This fragment was also evaluated
      against a commercially available enzyme-linked immunosorbent assay (ELISA). Two
      monoclonal antibodies were produced in mice immunized with the full-length
      protein, and each recognized a distinct epitope. These antibodies cross-reacted
      with proteins from other mycobacterial species and demonstrated variable sizes of
      the proteins expressed from these subspecies. Both antibodies were further
      analyzed, and their interaction with MAP1272c and MAP1204 was characterized by a
      solution-based, luminescent binding assay. These tools provide additional means
      to study a strong antigen of M. avium subsp. paratuberculosis.

PMID- 22593242
TI  - Distinct representations of attentional control during voluntary and stimulus
      driven shifts across objects and locations.
AB  - Efficient interaction with the sensory environment requires the rapid
      reallocation of attentional resources between spatial locations, perceptual
      features, and objects. It is still a matter of debate whether one single domain
      general network or multiple independent domain-specific networks mediate control
      during shifts of attention across features, locations, and objects. Here, we
      employed functional magnetic resonance imaging to directly compare the neural
      mechanisms controlling attention during voluntary and stimulus-driven shifts
      across objects and locations. Subjects either maintained or switched voluntarily
      and involuntarily their attention to objects located at the same or at a
      different visual location. Our data demonstrate shift-related activity in
      multiple frontoparietal, extrastriate visual, and default-mode network regions,
      several of which were commonly recruited by voluntary and stimulus-driven shifts
      between objects and locations. However, our results also revealed object- and
      location-selective activations, which, moreover, differed substantially between
      voluntary and stimulus-driven attention. These results suggest that voluntary and
      stimulus-driven shifts between objects and locations recruit partially
      overlapping, but also separable, cortical regions, implicating the parallel
      existence of domain-independent and domain-specific reconfiguration signals that
      initiate attention shifts in dependence of particular demands.

PMID- 22593244
TI  - Borderline personality disorder features and history of childhood maltreatment in
      mothers involved with child protective services.
AB  - This study examines the history of childhood maltreatment and Borderline
      Personality Disorder (BPD) symptoms in mothers whose children were removed from
      the home by Child Protective Services (CPS) to identify potential targets for
      future intervention efforts.  Forty-one mothers of children removed from the home
      due to abuse and/or neglect and 58 community-control mothers without CPS
      involvement were assessed for history of childhood maltreatment, alcohol and drug
      use, and BPD features. CPS-involved mothers scored significantly higher on
      measures of childhood maltreatment history and BPD features than did control
      mothers. The highest BPD scores were associated with the most severe histories of
      mothers' childhood maltreatment.  In total, 50% of CPS-involved mothers reported
      elevated BPD features, compared with 15% of control mothers.  Further, 19% of CPS
      involved mothers had self-reported scores consistent with a BPD diagnosis,
      compared with 4% of control mothers. BPD features rather than maltreatment
      history per se predicted maternal involvement with CPS, controlling for alcohol
      and drug use predictors. The present data suggest that evidence-based treatments
      to address BPD symptoms may be indicated for some CPS-involved parents.

PMID- 22593243
TI  - Thalamic network oscillations synchronize ontogenetic columns in the newborn rat
      barrel cortex.
AB  - Neocortical areas are organized in columns, which form the basic structural and
      functional modules of intracortical information processing. Using voltage
      sensitive dye imaging and simultaneous multi-channel extracellular recordings in
      the barrel cortex of newborn rats in vivo, we found that spontaneously occurring
      and whisker stimulation-induced gamma bursts followed by longer lasting spindle
      bursts were topographically organized in functional cortical columns already at
      the day of birth. Gamma bursts synchronized a cortical network of 300-400 um in
      diameter and were coherent with gamma activity recorded simultaneously in the
      thalamic ventral posterior medial (VPM) nucleus. Cortical gamma bursts could be
      elicited by focal electrical stimulation of the VPM. Whisker stimulation-induced
      spindle and gamma bursts and the majority of spontaneously occurring events were
      profoundly reduced by the local inactivation of the VPM, indicating that the
      thalamus is important to generate these activity patterns. Furthermore,
      inactivation of the barrel cortex with lidocaine reduced the gamma activity in
      the thalamus, suggesting that a cortico-thalamic feedback loop modulates this
      early thalamic network activity.

PMID- 22593245
TI  - In silico functional profiling of individual prostate cancer tumors: many genes,
      few functions.
AB  - BACKGROUND: Identification of genes that are differently expressed is a common
      approach used to analyze genetic mechanisms underlying cancer development.
      However, recent study results suggest that many such genes relate to a small
      number of biological functions. We hypothesized that analysis of these functions
      provides a better understanding of tumor biology than does actual identification
      of these genes. MATERIALS AND METHODS: We re-analyzed publicly available gene
      expression data for paired samples of prostate tumor and adjacent normal tissue
      from the same patients to identify genes differently expressed in individual
      tumors and then used them to identify the functions. RESULTS: We found
      significant interindividual variation in the type and the number of functions.
      After adjusting for redundancy and nonspecificity of the functional terms, we
      identified seven functions. Several of them showed a strong association with
      clinical traits, e.g. age at diagnosis, preoperative prostate-specific antigen
      concentration, Gleason grade, and biochemical recurrence. Actin cytoskeleton was
      the function most frequently associated with clinical traits. Of note, the
      association between function and clinical traits was much stronger than that
      between the genes differently expressed and those traits. CONCLUSION: Different
      prostate tumors differ in their functional profiles. Functions of differently
      expressed genes are strongly associated with clinical traits. This suggests that
      analysis of functions of differently expressed genes may provide a better
      description of tumor biology than does analysis of the respective genes.

PMID- 22593246
TI  - A genetic variant located in miR-423 is associated with reduced breast cancer
      risk.
AB  - BACKGROUND/AIM: Since microRNAs (miRNAs) act as translational regulators of
      multiple genes, single nucleotide polymorphisms (SNP) in them can have
      potentially wide-ranging effects. Using an association approach, this research
      examined the effects of the rs6505162 SNP, an A > C polymorphism located in the
      pre-miRNA region of miR-423, on breast cancer development. MATERIALS AND METHODS:
      Caucasian Australian women with breast cancer and controls matched for age and
      ethnicity were genotyped for rs6505162 and their genotypic and allelic
      frequencies analysed for significant differences. RESULTS: Analysis indicated
      that there were significant differences between the case and control populations
      (chi2 = 6.70, p = 0.035), with the CC genotype conferring reduced risk of breast
      cancer development (odds ratio = 0.50 95% confidence interval = 0.27-0.92, p =
      0.03). CONCLUSION: Further functional research is required to determine the
      mechanism of action of this SNP on miRNA function.

PMID- 22593247
TI  - Fully human targeted cytotoxic fusion proteins: new anticancer agents on the
      horizon.
AB  - Cytotoxic fusion proteins for tumor therapy are composed of an antibody-based
      targeting moiety and an effector molecule. Effectors may possess enzymatic
      activity confering cytoxicity after internalization or be an antibody-targeted
      death-receptor ligand that induces apoptosis after interaction with a death
      receptor. In this review, we focus on cytotoxic fusion proteins which, in most
      cases, are composed of fully human targeting and effector moieties. Regarding the
      first category, as outlined above, we focus on fusion proteins based on
      ribonucleases, granzyme B, apoptosis-inducing factor and death-associated protein
      kinases. The second category of fusion proteins makes use of cell-death inducing
      ligands such as tumor-necrosis factor, tumor necrosis factor alpha-related,
      apoptosis-inducing ligand fas ligand and a tumor-targeting antibody moiety. For
      the latter category, prodrug-related concepts are also covered. The critical
      issues to be resolved for improved efficacy and safety are discussed.

PMID- 22593249
TI  - Microarray-based mRNA expression profiling of leukemia cells treated with the
      flavonoid, casticin.
AB  - Natural polyphenols play an important role in tumor inhibition. We used a
      doxorubicin-sensitive acute T-lymphoblastic leukemia cell line (CCRF-CEM) and its
      multidrug-resistant subline (CEM/ADR5000) to evaluate the activity of 15 plant
      polyphenols isolated in our laboratory (hypericin and pseudohypericin,
      verbascoside, ellagic acid, casticin, kaempferol-3-O-(2'',6''-di-E-p-coumaroyl)
      glucopyranoside, kaempferol-3-O-(3,4-diacetyl-2,6-di-E-p-coumaroyl) 
      glucopyranoside, tiliroside, salvianolic acid B, oleuropein, rosmarinic acid,
      bergenin) or of others from commercial sources (curcumin, epigallocatechin-3
      gallate, silymarin). Casticin was the most potent compound (IC50 values of 0.28
      +/- 0.02 MUM in CCRF-CEM and 0.44 +/- 0.17 MUM in CEM/ADR5000 cells. The IC50
      values of the other compounds tested ranged from 1.52 MUM to 164.1 MUM. A
      microarray-based mRNA expression profiling of CCRF-CEM cells treated with
      casticin was performed in order to identify genes with altered expression
      following casticin treatment. Networks related to NF-kappaB, p38MAPK, histones H3
      and H4, and follicle stimulating hormone were identified.

PMID- 22593248
TI  - The spectra count label-free quantitation in cancer proteomics.
AB  - Mass spectrometry is used routinely for large-scale protein identification from
      complex biological mixtures. Recently, relative quantitation approach on the
      basis of spectra count has been applied in several cancer proteomic studies. In
      this review, we examine the mechanism of this technique and highlight several
      important parameters associated with its application.

PMID- 22593250
TI  - Modulation of apoptosis protein profiles--role of P-gp in HeLa cells exposed to
      doxorubicin.
AB  - As shown previously doxorubicin (1 MUM) plus sulindac (50 MUM) reduced the
      expression of ABCB1 (ATP-binding cassette, sub-family B (MDR/TAP), member 1) mRNA
      in HeLa cells and this effect was accompanied by increased apoptosis. The aim of
      this study was to define if the decrease of ABCB1 expression or blocking of P
      glycoprotein (P-gp) can affect the expression of the apoptotic genes determined
      with use of quantitative real time polymerase chain reaction (qRT-PCR). Western
      blot was used for visualization of chosen pro- and antiapoptotic proteins.
      Doxorubicin was the main compound which affected the apoptotic genes. The
      effectiveness of the drugs in reducing of P-gp function has been shown as not
      being related to the regulation of apoptotic gene transcription. In this
      experimental scheme, regulation of apoptotic gene transcription depended on the
      kind of P-gp modulator.

PMID- 22593251
TI  - Obesity, feet, and the impact on health care.

PMID- 22593252
TI  - Minimally invasive surgery.

PMID- 22593253
TI  - Stability-indicating method for simultaneous estimation of olmesartan medoxomile,
      amlodipine besylate and hydrochlorothiazide by RP-HPLC in tablet dosage form.
AB  - A simple, specific, accurate and precise stability-indicating reversed-phase high
      performance liquid chromatographic method was developed for simultaneous
      estimation of olmesartan medoxomile (OLME), amlodipine besylate (AMLO) and
      hydrochlorothiazide (HCTZ) in tablet dosage form. The method was developed using
      an RP C18 base deactivated silica column (250 * 4.6 mm, 5 um) with a mobile phase
      consisting of triethylamine (pH 3.0) adjusted with orthophosphoric acid (A) and
      acetonitrile (B), with a timed gradient program of T/%B: 0/30, 7/70, 8/30, 10/30
      with a flow rate of 1.4 mL/min. Ultraviolet detection was used at 236 nm. The
      retention times for OLME, AMLO and HCTZ were found to be 6.72, 4.28 and 2.30,
      respectively. The proposed method was validated for precision, accuracy,
      linearity, range, robustness, ruggedness and force degradation study. The
      calibration curves of OLME, AMLO and HCTZ were linear over the range of 50-150,
      12.5-37.5 and 31-93 ug/mL, respectively. The method was found to be sensitive.
      The limits of detection of OLME, AMLO and HCTZ were determined 0.19, 0.16 and
      0.22 ug/mL and limits of quantification of OLME, AMLO and HCTZ were determined
      0.57, 0.49 and 0.66, respectively. Forced degradation study was performed
      according to International Conference on Harmonization guidelines.

PMID- 22593257
TI  - Retracted: Open-heart surgery in patients with liver cirrhosis [Eur J
      Cardiothorac Surg 2007;31:1094-8].

PMID- 22593258
TI  - Univentricular heart and Fontan staging: analysis of factors impacting on body
      growth.
AB  - OBJECTIVES: The optimal timing of the Fontan staging for a univentricular heart
      and its impact on growth remains debateable. In a Fontan cohort, the influence of
      staged interventions and patient factors on somatic development was explored.
      METHODS: We reviewed 64 total cavopulmonary connection (TCPC) patients treated
      since 1992. Serial anthropometric parameters recorded from birth to the latest
      follow-up (mean 12.5 +/- 6.1 years) and at each intervention [neonatal surgery,
      bidirectional cavopulmonary anastomosis (BCPA), TCPC, catheter treatment] were
      converted to z-scores. The influence of saturation, heart failure treatment and
      surgery intervals on growth was determined. RESULTS: The mean z-scores for weight
      and height changed significantly at each surgery up to the TCPC (-0.3 +/- 1.2 and
      0 +/- 1 at birth, -1.3 +/- 1.9 and -0.9 +/- 1.7 at neonatal surgery, -2.1 +/- 1.2
      and -1.6 +/- 1.3 at the BCPA, -1.2 +/- 1.3 and -0.7 +/- 1.4 at the TCPC for
      weight and height, respectively; P < 0.05 for each interval), with the largest
      decline before the BCPA, and the most marked improvement before the TCPC. Z
      scores did not change significantly after the TCPC. Younger age at the BCPA had a
      positive influence on the weight z-score at the TCPC (P < 0.05); somatic growth
      at the latest follow-up (FU) was negatively influenced by heart failure treatment
      (P < 0.05). CONCLUSIONS: Body growth is severely impaired in Fontan patients. A
      close interstage follow-up between the first surgery and the BCPA must be
      targeted at optimizing nutritional support to counter the important growth
      retardation occurring before the BCPA. The better catch-up growth at the TCPC
      when the BCPA is performed earlier in life supports the current trend to perform
      the BCPA at a younger age. Heart failure treatment after a Fontan completion is
      independently associated with decreased late somatic development.

PMID- 22593259
TI  - Assessment of aortopulmonary collateral flow and pulmonary vascular growth using
      a 3.0 T magnetic resonance imaging system in patients who underwent bidirectional
      Glenn shunting.
AB  - OBJECTIVES: To explore the feasibility of evaluating the aortopulmonary
      collateral flow (APCF) and pulmonary vascular growth of patients who underwent
      bidirectional Glenn shunting (BGS) using phase-contrast magnetic resonance
      imaging (PC-MRI) and contrast-enhanced magnetic resonance imaging (CE-MRI).
      METHODS: Blood flow measurements of the great vessels of the body were recorded
      in 22 post-BGS patients using 3.0 T PC-MRI. Right and left pulmonary blood flow
      (Q(P)), stroke volume (SV) of the ascending aorta (Q(S)), blood flow of
      descending aorta (Q(d)) and venous return of the superior and inferior venae
      cavae (Q(V)) per minute were calculated using the Report Card software. APCF was
      equal to the difference between Q(S) and Q(V). The parameters for pulmonary
      vascular growth were assessed using CE-MRI. The relationship between pulmonary
      vascular growth and APCF was evaluated using correlation analysis. A comparative
      analysis was conducted between the MRI results and the results of five cases who
      underwent cardiac catheterization and 10 cases who underwent angiography.
      RESULTS: Estimated APCF ranged from 0.23 to 1.63 l/(min/m(2)), accounting for 5
      44% of Q(S). Morphologic abnormalities such as pulmonary stenosis, dilatation and
      thrombosis were clearly visualized through CE-MRI. Significant differences in
      individual pulmonary artery growth were observed. A significant negative
      correlation was found between APCF and the pulmonary artery index (PAI; r = 
      0.461, P = 0.031) when the McGoon rate was 2.04 +/- 0.59 and the PAI was 253.27
      +/- 85.86 mm(2)/m(2). Good consistency or relativity was found between cardiac
      catheterization, angiography and MRI. CONCLUSIONS: Assessing the APCF and
      parameters for pulmonary vascular growth in patients who underwent BGS is
      feasible using 3.0 T PC-MRI integrated with CE-MRI, which may play an important
      role in clinical and therapeutic decision-making and prognostic evaluation.

PMID- 22593260
TI  - Pulmonary endarterectomy: outcomes in patients aged >70.
AB  - OBJECTIVES: Advanced age is not a barrier to cardiac surgery, with reports
      demonstrating excellent outcomes, but the effect of age on more complex surgery
      has not been studied. We assessed the outcomes of pulmonary endarterectomy (PEA)
      surgery in patients aged >70. METHODS: A retrospective review of consecutive
      patients who underwent PEA between January 2006 and March 2011 at a national
      referral centre. The total cohort was dichotomized according to age on the day of
      surgery, either below or above 70 years. Outcomes were in-hospital mortality,
      overall survival and the length of ICU and hospital stays. RESULTS: Four hundred
      and eleven patients underwent PEA during the 5-year period. The mean age was 56.9
      years (range, 17-84 years). The in-hospital mortality was 14 of 308 (4.6%) for
      patients <70 years compared with 8 of 103 (7.8%) for patients >=70 years (P =
      0.21). The overall survival at 1, 2 and 3 years was 91.4, 89.9 and 87.7% in the
      <70-year old group and 85.9, 84.1 and 84.1% in the >70-year old group (log-rank
      test, P = 0.07), respectively. The length of ICU and in-hospital stays was longer
      in the >70-year old group, by 1 and 2 days, respectively (P = 0.005 and 0.001).
      CONCLUSIONS: PEA surgery in patients >=70 years is safe and carries a comparable
      risk of early mortality in younger patients, but there is an increase in resource
      use due to longer ICU and hospital stays. Advanced age should be taken into
      consideration when assessing suitability for PEA, but age per se should not be a
      contraindication to surgery.

PMID- 22593261
TI  - Adequacy of the emergency point-of-care ultrasound core curriculum for the local
      burden of disease in South Africa.
AB  - OBJECTIVE: This prospective cross-sectional study assesses the adequacy of the
      current South African emergency point-of-care ultrasound (EPCUS) core curriculum
      against the local burden of disease. METHOD: Patients presenting to five
      Emergency Centres during July 2011 were eligible for inclusion. Patients under
      the age of 12, after-hour presentations, missing folders and folders with
      incomplete notes were excluded. Emergency physicians with EPCUS exposure were
      responsible for data collection. They were all blinded to the study's aim.
      Summary statistics describe the proportion of clinical cases and procedures for
      which EPCUS was used. One investigator assessed the adequacy of the curriculum by
      matching the clinical indications of each module with the presenting complaint
      and final diagnosis of each patient. The ultrasound modules were ranked according
      to the frequency of their clinical indications. kappa-Statistics are reported on
      10% randomly selected cases to quantify interobserver agreement. RESULTS: The
      study included 2971 patients. Ultrasound assisted with diagnosis in 384 (12.92%)
      patients and in 34 (1.14%) procedures. A total of 1933 EPCUS procedures were
      indicated in 1844 (66.07%) patients. The five most frequently indicated modules
      were pulmonary, musculoskeletal, cardiac, focused assessment with sonography of
      HIV/tuberculosis co-infection and renal. The interobserver agreement (kappa) was
      0.602 (95% CI 0.559 to 0.645). CONCLUSIONS: This study was an attempt to ensure
      an evidence-based approach to assess the adequacy of the EPCUS core curriculum in
      South Africa. The results illustrate that our local burden of disease may require
      a change of the current core curriculum.

PMID- 22593262
TI  - A reliable way of reducing Colles' fractures.

PMID- 22593263
TI  - Preventive behaviours against radiation and related factors among general workers
      after Fukushima's nuclear disasters.
AB  - BACKGROUND: The nuclear power plant accidents in Fukushima resulted in a
      widespread release of radioactive substances in the Fukushima prefecture. AIM: To
      clarify what factors led to precautions among general workers who displayed
      preventive behaviours against radiation following the nuclear disasters in
      Fukushima. METHODS: Descriptive study of preventive behaviours among general
      workers 3-5 months following the nuclear disasters. The subjects were 1394
      regular workers who took part in radiation seminars conducted by the Fukushima
      Occupational Health Promotion Center between July and August 2011. Of 1217
      responses, 1110 eligible responses were included in this study. This anonymous
      questionnaire survey was asking for characteristics and questions on preventive
      behaviours following the nuclear disasters. The authors assessed the contribution
      of each variable by a logistic regression analysis. RESULTS: Keeping track of
      environmental radiation levels and washing hands and gargling were significantly
      more frequent among female subjects, older age and workers residing up to
      approximately 80 km away from the power plants. Washing hands and gargling were
      also related with living with children. Wearing a mask when leaving home and
      buying bottled water were significantly more often observed with female subjects
      and workers residing up to 80 km. Refraining from going outdoors was positively
      associated with workers residing up to 80 km and workers living with children.
      CONCLUSIONS: These results provide information that may help with the targeting
      of health information after a nuclear disaster. This may contribute to
      determining an order of priority when distributing information after a nuclear
      disaster.

PMID- 22593264
TI  - Ambulance services in London and Great Britain from 1860 until today: a glimpse
      of history gleaned mainly from the pages of contemporary journals.
AB  - Little has been published on the subject of civil ambulance services and their
      development from the mid-19th century in the UK until modern times. There is
      limited secondary literature available which provides useful background
      information on the subject and most organisations may give brief histories of
      their early days but these sources lack historical adequacy in terms of detail.
      This article shows part of the uncertain path which the history followed towards
      the service which we enjoy today. From the pages of the British Medical Journal
      and the Lancet and Hansard, the battle to set up the service is followed and an
      indication of the drivers towards change over the period is revealed in the
      attitudes expressed. In particular, the two World Wars are seen to be the
      stepwise stimuli to providing a necessary service to the British population where
      the will to achieve this had hitherto been lacking at a parliamentary level. The
      history of the London Ambulance Service is chosen because more is written about
      it in these journals but services in other British cities and the USA are
      mentioned since they played a part in influencing change.

PMID- 22593265
TI  - Bilateral hilar syndrome.

PMID- 22593266
TI  - Heart-type fatty acid binding protein as an early marker for myocardial
      infarction: systematic review and meta-analysis.
AB  - BACKGROUND: Heart-type fatty acid binding protein (H-FABP) has been proposed as
      an early biomarker of myocardial infarction (MI). The authors aimed to undertake
      a systematic review and meta-analysis to estimate the early sensitivity and
      specificity of quantitative and qualitative H-FABP assays. METHODS: The authors
      undertook a systematic search using electronic databases, citation lists and
      expert contacts to identify all diagnostic cohort studies of patients presenting
      with suspected acute coronary syndrome that compared H-FABP at presentation to a
      reference standard based on the Universal definition of MI. Study quality was
      assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. Meta
      analysis was conducted using Bayesian Markov chain Monte Carlo simulation.
      RESULTS: The authors included eight studies of quantitative H-FABP and nine
      studies of qualitative H-FABP. The summary estimates of sensitivity and
      specificity were 81% (95% prediction interval 50% to 95%) and 80% (26% to 98%)
      respectively for the quantitative assays and 68% (11% to 97%) and 92% (20% to
      100%) respectively for the qualitative assays. Four studies reported the
      sensitivity of troponin and H-FABP at presentation in which the combination was
      considered positive if either test was positive. The addition of H-FABP to
      troponin increased sensitivity from 42-75% to 76-97% but decreased specificity
      from 94-100% to 65-93%. CONCLUSION: H-FABP has modest sensitivity and specificity
      for MI at presentation but estimates are subject to substantial uncertainty and
      primary data are subject to substantial heterogeneity. H-FABP may have a role
      alongside troponin in improving early sensitivity but comparison with high
      sensitivity troponin assays is required.

PMID- 22593267
TI  - Van earthquake: development of emergency medicine in a country.

PMID- 22593268
TI  - An evidence based blunt trauma protocol.
AB  - OBJECTIVE: Currently CT is rapidly implemented in the evaluation of trauma
      patients. In anticipation of a large international multicentre trial, this
      study's aim was to evaluate the clinical feasibility of a new diagnostic
      protocol, used for the primary radiological evaluation in adult blunt high-energy
      trauma patients, especially for the use of CT. METHODS: An evidence-based flow
      chart was created with criteria based on trauma mechanism, physical examination
      and laboratory analyses to indicate appropriateness of conventional radiography
      (CR), sonography and CT of head, cervical spine and trunk. To evaluate this
      protocol, the authors prospectively included 81 consecutive patients. Collected
      data included protocol adherence and number and type of performed CR and CT
      scans. The authors also determined the time needed to perform radiological
      investigations, adverse events in the CT room and clinically relevant missed
      injuries after 1-month clinical follow-up. RESULTS: There was 99% adherence to
      the protocol concerning CT. Seventy-nine patients (98%) received one or more CT
      scans: 72 (89%) had thoracoabdominal, 78 (96%) cervical spine and 54 (67%) had
      cranial CT. In 30 patients, one or more CT scans of body regions could be
      omitted. In 38%, CR was wrongly omitted or performed incorrectly at a variance
      with the protocol. No major adverse events occurred in the CT room and no
      clinically relevant injuries were missed. CONCLUSIONS: The authors introduced a
      diagnostic protocol that seems feasible and safe for the evaluation of adult
      blunt high-energy trauma patients. Implementation of this protocol has the
      potential to reduce unnecessary radiological investigations, especially CT scans.

PMID- 22593269
TI  - Resistance to obesity by repression of VEGF gene expression through induction of
      brown-like adipocyte differentiation.
AB  - Adipose tissues are classified into white adipose tissue (WAT) and brown adipose
      tissue (BAT). WAT is responsible for energy storage, and malfunction is
      associated with obesity. BAT, on the contrary, consumes fat to generate heat
      through uncoupling mitochondrial respiration and is important in body weight
      control. Vascular endothelial growth factor (VEGF)-A is the founding member of
      the VEGF family and has been found highly expressed in adipose tissue. A genetic
      mouse model of an inducible VEGF (VEGF-A) repression system was used to study
      VEGF-regulated energy metabolism in WAT. VEGF-repressed mice demonstrated lower
      food efficiency, lower body weight, and resistance to high-fat diet-induced
      obesity. Repression of VEGF expression caused morphological and molecular changes
      in adipose tissues. VEGF repression induced brown-like adipocyte development in
      WAT, up-regulation of BAT-specific genes including PRDM16, GATA-1, BMP-7, CIDEA,
      and UCP-1 and down-regulation of leptin, a WAT-specific gene. VEGF repression up
      regulated expression of VEGF-B and its downstream fatty acid transport proteins.
      Relative levels of VEGF/VEGF-B may be important switches in energy metabolism and
      of pharmaceutical significances.

PMID- 22593270
TI  - Mice lacking the calcineurin inhibitor Rcan2 have an isolated defect of
      osteoblast function.
AB  - Calcineurin-nuclear factor of activated T cells signaling controls the
      differentiation and function of osteoclasts and osteoblasts, and regulator of
      calcineurin-2 (Rcan2) is a physiological inhibitor of this pathway. Rcan2
      expression is regulated by T(3), which also has a central role in skeletal
      development and bone turnover. To investigate the role of Rcan2 in bone
      development and maintenance, we characterized Rcan2(-/-) mice and determined its
      skeletal expression in T(3) receptor (TR) knockout and thyroid-manipulated mice.
      Rcan2(-/-) mice had normal linear growth but displayed delayed intramembranous
      ossification, impaired cortical bone formation, and reduced bone mineral accrual
      during development as well as increased mineralization of adult bone. These
      abnormalities resulted from an isolated defect in osteoblast function and are
      similar to skeletal phenotypes of mice lacking the type 2 deiodinase thyroid
      hormone activating enzyme or with dominant-negative mutations of TRalpha, the
      predominant TR isoform in bone. Rcan2 mRNA was expressed in primary osteoclasts
      and osteoblasts, and its expression in bone was differentially regulated in
      TRalpha and TRbeta knockout and thyroid-manipulated mice. However, in primary
      osteoblast cultures, T(3) treatment did not affect Rcan2 mRNA expression or
      nuclear factor of activated T cells c1 expression and phosphorylation. Overall,
      these studies establish that Rcan2 regulates osteoblast function and its
      expression in bone is regulated by thyroid status in vivo.

PMID- 22593271
TI  - In vivo changes in central and peripheral insulin sensitivity in a large animal
      model of obesity.
AB  - Obesity disrupts homeostatic energy balance circuits leading to insulin
      resistance. Here we examined in vivo peripheral and central insulin sensitivity,
      and whether central insensitivity in terms of the voluntary food intake (VFI)
      response occurs within the hypothalamus or at blood-brain transfer level, during
      obesity and after subsequent weight loss. Sheep with intracerebroventricular
      (i.c.v.) cannulae were fed complete diet for 40 wk ad libitum (obese group) or at
      control level (controls). Thereafter, obese sheep were food restricted (slimmers)
      and controls fed ad libitum (fatteners) for 16 wk. Dual-energy x-ray
      absorptiometry (DEXA) measured total body fat, insulin analyses in blood and
      cerebrospinal fluid (CSF) assessed blood-brain transfer, i.v. glucose tolerance
      test (GTT) and insulin tolerance test (ITT) measured peripheral insulin
      sensitivity, and VFI responses to icv insulin assessed intrahypothalamic
      sensitivity. Insulinemia was higher in obese than controls; plasma insulin
      correlated with DEXA body fat and CSF insulin. Insulinemia was higher in
      fatteners than slimmers but ratio of CSF to plasma insulin correlated only in
      fatteners. Plasma glucose baseline and area under the curve were higher during
      GTT and ITT in obese than controls and during ITT in fatteners than slimmers. GTT
      and ITT glucose area under the curve correlated with DEXA body fat. VFI decreased
      after i.c.v. insulin, with response magnitude correlating negatively with DEXA
      body fat. Overall, insulin resistance developed first in the periphery and then
      within the brain, thereafter correlating with adiposity; central resistance in
      terms of VFI response resulted from intrahypothalamic insensitivity rather than
      impaired blood-brain transfer; modest weight loss improved peripheral but not
      central insulin sensitivity and induced central hypoinsulinemia.

PMID- 22593429
TI  - Obesity, type 2 diabetes, and cancer: the insulin and IGF connection.
AB  - Epidemiological studies suggest a positive association between obesity and type 2
      diabetes mellitus (T2D) with the risk of cancer and cancer-related mortality.
      Insulin resistance, hyperinsulinemia, increased levels of IGF, elevated levels of
      steroid and peptide hormones, and inflammatory markers appear to play a role in
      the connection between these different diseases. Medications, such as metformin
      and exogenous insulin, used to treat T2D may affect the risk of cancer and cancer
      related mortality. Newer therapies targeting the insulin and IGF1 systems are
      being developed for use in cancer therapy.

PMID- 22593272
TI  - Induction of gastrin expression in gastrointestinal cells by hypoxia or cobalt is
      independent of hypoxia-inducible factor (HIF).
AB  - Gastrin and its precursors have been shown to promote mitogenesis and
      angiogenesis in gastrointestinal tumors. Hypoxia stimulates tumor growth, but its
      effect on gastrin gene regulation has not been examined in detail. Here we have
      investigated the effect of hypoxia on the transcription of the gastrin gene in
      human gastric cancer (AGS) cells. Gastrin mRNA was measured by real-time PCR,
      gastrin peptides were measured by RIA, and gastrin promoter activity was measured
      by dual-luciferase reporter assay. Exposure to a low oxygen concentration (1%)
      increased gastrin mRNA concentrations in wild-type AGS cells (AGS) and in AGS
      cells overexpressing the gastrin receptor (AGS-cholecystokinin receptor 2) by 2.1
      +/- 0.4- and 4.1 +/- 0.3-fold (P < 0.05), respectively. The hypoxia mimetic,
      cobalt chloride (300 MUM), increased gastrin promoter activity in AGS cells by
      2.4 +/- 0.3-fold (P < 0.05), and in AGS-cholecystokinin receptor 2 cells by 4.0
      +/- 0.3-fold (P < 0.05), respectively. The observations that either deletion from
      the gastrin promoter of the putative binding sites for the transcription factor
      hypoxia-inducible factor 1 (HIF-1) or knockdown of either the HIF-1alpha or HIF
      1beta subunit did not affect gastrin promoter inducibility under hypoxia
      indicated that the hypoxic activation of the gastrin gene is likely HIF
      independent. Mutational analysis of previously identified Sp1 regulatory elements
      in the gastrin promoter also failed to abrogate the induction of promoter
      activity by hypoxia. The observations that hypoxia up-regulates the gastrin gene
      in AGS cells by HIF-independent mechanisms, and that this effect is enhanced by
      the presence of gastrin receptors, provide potential targets for gastrointestinal
      cancer therapy.

PMID- 22593430
TI  - Amifostine-doxorubicin association causes long-term prepubertal spermatogonia DNA
      damage and early developmental arrest.
AB  - BACKGROUND: In a previous study, we found that amifostine provides some
      protection to the seminiferous epithelium of prepubertal doxorubicin-treated male
      rats but does not improve their fertility status as adults. Based on these
      results, a long-term study was undertaken to evaluate the DNA damage caused to
      spermatogonia and the consequences for embryo development. METHODS: Twenty-four
      male prepubertal rats (30-day-old) were divided into four equal groups and
      treated with: doxorubicin (D--5 mg/kg), amifostine (A--400 mg/kg),
      amifostine/doxorubicin (AD--amifostine 15 min before doxorubicin) and control (C-
      0.9% saline solution). Sixty-four days after the treatment, animals were
      euthanized and the testes and epididymides were excised. The testes were fixed in
      Bouin's solution and historesin-embedded for histopathological analysis.
      Spermatozoa from the cauda epididymides were collected for chromatin structure
      analyses (Comet Assay and SCSATM). Adult rats (100-day-old) were mated with
      fertile females for embryo analyses on 2.5, 4.5 and 20 days post-coitum (d.p.c.).
      RESULTS: The seminiferous epithelium histopathology of AD group was better
      preserved compared with the D group. On the other hand, rats from the D and AD
      groups presented an increased percentage of sperm DNA strand breaks, as assessed
      by the comet assay, as well as an increased level of sperm chromatin
      denaturation, as assessed by the SCSATM assay. In amifostine-treated groups (A
      and AD) there was a significant increase in the number of arrested embryos, as
      observed by the number of oocytes/zygotes on 2.5 d.p.c., when compared with
      control and doxorubicin groups; however, this number was increased when the AD
      group was compared with the A group. CONCLUSIONS: These results raise a concern
      about the effects of the association of these two drugs on the germ cell genome.
      Amifostine-doxorubicin-exposed rat spermatogonia produced long-term damage on
      sperm DNA, compromised conceptus development and reduced pregnancy outcome.

PMID- 22593431
TI  - The preconception diet is associated with the chance of ongoing pregnancy in
      women undergoing IVF/ICSI treatment.
AB  - BACKGROUND: Subfertility and poor nutrition are increasing problems in Western
      countries. Moreover, nutrition affects fertility in both women and men. In this
      study, we investigate the association between adherence to general dietary
      recommendations in couples undergoing IVF/ICSI treatment and the chance of
      ongoing pregnancy. METHODS: Between October 2007 and October 2010, couples
      planning pregnancy visiting the outpatient clinic of the Department of Obstetrics
      and Gynaecology of the Erasmus Medical Centre in Rotterdam, the Netherlands were
      offered preconception counselling. Self-administered questionnaires on general
      characteristics and diet were completed and checked during the visit. Six
      questions, based on dietary recommendations of the Netherlands Nutrition Centre,
      covered the intake of six main food groups (fruits, vegetables, meat, fish, whole
      wheat products and fats). Using the questionnaire results, we calculated the
      Preconception Dietary Risk score (PDR), providing an estimate of nutritional
      habits. Dietary quality increases with an increasing PDR score. We define ongoing
      pregnancy as an intrauterine pregnancy with positive heart action confirmed by
      ultrasound. For this analysis we selected all couples (n=199) who underwent a
      first IVF/ICSI treatment within 6 months after preconception counselling. We
      applied adjusted logistic regression analysis on the outcomes of interest using
      SPSS. RESULTS: After adjustment for age of the woman, smoking of the woman, PDR
      of the partner, BMI of the couple and treatment indication we show an association
      between the PDR of the woman and the chance of ongoing pregnancy after IVF/ICSI
      treatment (odds ratio 1.65, confidence interval: 1.08-2.52; P=0.02]. Thus, a one
      point increase in the PDR score associates with a 65% increased chance of ongoing
      pregnancy. CONCLUSIONS: Our results show that increasing adherence to Dutch
      dietary recommendations in women undergoing IVF/ICSI treatment increases the
      chance of ongoing pregnancy. These data warrant further confirmation in couples
      achieving a spontaneous pregnancy and in randomized controlled trials.

PMID- 22593433
TI  - Down-regulation of the epidermal growth factor receptor by altering N
      glycosylation: emerging role of beta1,4-galactosyltransferases.
AB  - BACKGROUND/AIM: Blocking N-glycosylation of the epidermal growth factor receptor
      (EGFR) by tunicamycin inhibits its cellular accumulation. Due to the toxic
      potential of this drug, finding less drastic routes to reduce EGFR expression is
      desirable. MATERIALS AND METHODS: Four glycosylation mutants of Chinese hamster
      ovary (CHO) cells with defects in N-glycan processing and branch-end maturation
      were tested for EGFR gene expression, production, functionality and routing after
      transfection with a vector encoding for human EGFR. RESULTS: Lack of conversion
      of paucimannosidic to hybrid/complex-type N-glycans and drastic reductions in
      sialylation/galactosylation did not lead to major effects. In contrast, EGFR
      expression in a mutant with reduced presence of beta1,4-galactosyltransferases-I
      VI was markedly reduced. Misrouting or defects in transfection/transcription were
      excluded. CONCLUSION: beta1,4-Galactosyl-transferases warrant for further
      attention as effector(s) in order to attenuate EGFR-dependent signaling.

PMID- 22593432
TI  - Amphiregulin promotes the maturation of oocytes isolated from the small antral
      follicles of the rhesus macaque.
AB  - BACKGROUND: In non-primates, the epidermal growth factor (EGF) and EGF-related
      ligands such as amphiregulin (AREG) serve as critical intermediates between the
      theca/mural cells and the cumulus-oocyte-complex (COC) following the mid-cycle LH
      surge. Studies were designed in primates (1) to analyze AREG levels in follicular
      fluid (follicular fluid) obtained from pre-ovulatory follicles, as well as (2) to
      assess dose-dependent effects of AREG on oocytes from small antral follicles
      (SAFs) during culture, including meiotic and cytoplasmic maturation. METHODS:
      Controlled ovulation protocols were performed on rhesus monkeys (n=12) to
      determine AREG content within the single, naturally selected dominant follicle
      after an ovulatory stimulus. Using healthy COCs (n=271) obtained from SAFs during
      spontaneous cycles (n=27), in vitro maturation (IVM) was performed in the absence
      or presence of physiological concentrations of AREG (10 or 100 ng/ml) with or
      without gonadotrophins (FSH, 75 mIU/ml; LH, 75 mIU/ml). At the end of the culture
      period, oocyte meiotic maturation was evaluated and ICSI was performed (n=111),
      from which fertilization and early embryo development was followed in vitro.
      RESULTS: AREG levels in follicular fluid from pre-ovulatory follicles increased
      (P<0.05) following an ovulatory bolus of hCG at 12, 24 and 36 h post-treatment.
      At 12 h post-hCG, AREG levels in follicular fluid ranged from 4.8 to 121.4 ng/ml.
      Rhesus macaque COCs incubated with 10 ng/ml AREG in the presence of
      gonadotrophins displayed an increased percentage of oocytes that progressed to
      the metaphase II (MII) stage of meiosis (82 versus 56%, P<0.05) and a decreased
      percentage of metaphase I (MI) oocytes (2 versus 23%, P<0.05) relative to
      controls, respectively. The percentage of either MI or MII oocytes at the end of
      the culture period was not different between oocytes cultured with 100 ng/ml AREG
      or in media alone. Fertilization and first cleavage rates obtained by ICSI of all
      IVM MII oocytes were 93 and 98%, respectively, and did not vary among treatment
      groups. Of the MII oocytes that fertilized (n=103), 37 were randomly selected and
      maintained in culture to assess developmental potential. A total of 13 early
      blastocysts were obtained, with four embryos developing to expanded blastocysts.
      CONCLUSIONS: These data indicate that AREG levels increase in rhesus macaque pre
      ovulatory follicles after an ovulatory stimulus, and a specific concentration of
      AREG (10 ng/ml) enhances rhesus macaque oocyte nuclear maturation but not
      cytoplasmic maturation from SAFs obtained during the natural menstrual cycle.
      However, owing to the small number of samples in some treatment groups, further
      studies are now required.

PMID- 22593434
TI  - Inhibition of metastasis of circulating human prostate cancer cells in the chick
      embryo by an extracellular matrix produced by foreskin fibroblasts in culture.
AB  - We have previously demonstrated the increased metastatic potential of human
      prostate cancer circulating tumor cells (CTC), compared to their parental cells,
      in both orthotopic mouse models and the chick embryo model. In the current study,
      we asked whether an extracellular matrix (ECM), produced by human foreskin
      fibroblasts in culture, could inhibit PC-3 human prostate cancer CTC metastasis
      in the chick embryo model. The chorioallantoic membranes (CAM) of 18 chicken
      embryos were inoculated with either PC-3 human prostate cancer cells or PC-3
      CTCs, both stably expressing green fluorescent protein (GFP). Embryos were
      divided into six groups: PC-3 parental-cell control; PC-3 plus soluble ECM; PC-3
      parental cells plus semi-solid ECM; PC-3 CTC control; PC-3 CTC plus soluble ECM,
      and PC-3 CTC plus semi-solid ECM. Twelve hours following inoculation of the
      cells, a single dose of 100 MUl of either soluble or semi-solid ECM was added to
      the appropriate group. Embryo brains were removed on day 8 post-inoculation, and
      were processed for cryosectioning. Imaging was performed on the cryosections
      using a scanning laser microscope in order to count metastatic foci. PC-3
      controls had an average of 11.1 metastatic foci compared to 2.55 in the PC-3 plus
      soluble ECM group and 2.76 (p<0.0001) in the PC-3 plus semi-solid ECM group
      (p<0.0001). ECM treatment had even greater efficacy on the CTC cells, with an
      average of 30.9 metastatic foci in the CTC controls compared to 4.38 in the CTC
      plus soluble ECM group (p<0.0001) and 4.18 in the CTC plus semi-solid ECM group
      (p<0.0001). The results demonstrate that reduction of CTC metastatic potential is
      possible, in this case with an ECM produced by human foreskin fibroblasts in
      culture.

PMID- 22593435
TI  - Interactions between normal human fibroblasts and human prostate cancer cells in
      a co-culture system.
AB  - BACKGROUND: Stroma affects the development and the structure of many organs and
      plays an important role in regulating epithelial malignancies, including those
      derived from the prostate. Fibroblasts represent the major cell type of the
      stromal compartment. Aiming at clarifying the relationships between normal
      fibroblasts and epithelial cancer cells, we utilized a co-culture system, which
      included both androgen-sensitive (LNCaP) and -insensitive (PC-3, DU-145) prostate
      cancer cell lines and a human gingival fibroblast cell line (FG). MATERIALS AND
      METHODS: The morphological aspects of the cultures were analyzed under an
      inverted phase-contrast microscope; the proliferation in conditioned media (CM)
      was assessed by cell counts, and the E-cadherin expression was evaluated by
      immunocytochemistry. RESULTS: In co-culture, androgen-sensitive LNCaP cells grew
      in a network on the top of the monolayer formed by FG, while colonies of androgen
      insensitive PC-3 and DU-145 cells were surrounded by FG cells. After six days,
      the LNCaP cell number was apparently lower in the co-cultures than in the plates
      where they grew alone. Both LNCaP and FG cells underwent morphological changes.
      After the same period of time, the growth of PC-3 and DU-145 cells overcame the
      growth of FG cells, which were almost abolished. The CM of FG inhibited the
      proliferation of LNCaP cells, after three days by 33% (p<0.01) and after six days
      by up to 82% (p<0.01), but had no effect on the PC-3 and DU-145 cell growth. The
      CM of all three prostate cancer cell lines reduced the growth of FG. Growth
      reduction in DU-145 cells was the most effective (50% inhibition after three
      days, p<0.01, and 55% after six days, p<0.01). FG did not express E-cadherin,
      while strong E-cadherin staining was detected in LNCaP cells. PC-3 cells
      exhibited E-cadherin nuclear staining, while sporadic membrane expression of the
      specific protein was observed in DU-145 cells. In co-culture, there seemed to be
      a reduction in the nuclear E-cadherin reactivity of PC-3 cells. CONCLUSION: Our
      data confirm the existence of a dialogue between normal fibroblasts and prostate
      cancer cells, which results in both a peculiar modality of growth and a
      regulation of proliferation, probably due to factors secreted in the culture
      medium. The variation in E-cadherin expression found in PC-3 cells co-cultured
      with FG merits further investigation.

PMID- 22593436
TI  - The expression of HMGA2 varies strongly among colon carcinomas.
AB  - BACKGROUND: The expression of high mobility group protein AT-hook2 (HMGA2)
      indicates a worse prognosis in many epithelial malignancies, such as colon
      cancer. The present study addresses methodological aspects, as well as the
      genetic background, of the HMGA2 expression in colon cancer. MATERIALS AND
      METHODS: Samples of 38 colon carcinomas were studied for the expression of HMGA2
      by quantitative Real-Time PCR (qRT-PCR). In selected cases, immunohistochemistry
      (IHC) was also performed. RESULTS: The overexpression of HMGA2, compared to
      adjacent mucosa, is not consistent among colon carcinomas: Only a minority of
      carcinomas strongly overexpressed HMGA2, but in no more than 50% of the tumors
      did the expression exceed the average value in mucosa samples. qRT-PCR clearly
      reveals a continuum between cases with high and low expression. CONCLUSION: For
      HMGA2-based risk assessment, continuous rather than discontinuous models seem to
      be most appropriate. However, in daily practice, IHC seems to be a suitable
      method to stratify for high-risk patients.

PMID- 22593437
TI  - Autoxidation of gallic acid induces ROS-dependent death in human prostate cancer
      LNCaP cells.
AB  - BACKGROUND: Prostate cancer is the second most common cause of mortality. Gallic
      acid (GA) is a natural polyphenol, and we tested its in-vitro cytotoxicity after
      24 h in prostate cancer LNCaP cells. MATERIALS AND METHODS: GA autoxidation was
      measured fluorimetrically for H(2)O(2), and O(2)(*-) radicals by
      chemiluminescence. Intracellular reactive oxygen species (ROS) levels were
      detected with 2',7'-dichlorodihydrofluorescein diacetate. Cytotoxicity was
      evaluated by crystal-violet, while apoptosis and mitochondrial membrane potential
      were determined by flow cytometry. Cytochrome c release was detected by enzyme
      linked immunosorbent assay, and caspase-8, -9 and -3 activities were measured
      calorimetrically. RESULTS: GA autoxidation produced significant levels of
      H(2)O(2) and O2.-. Increased intracellular ROS levels with GA were reduced by N
      acetyl-L-cysteine (NAC) and L-glutathione (GSH). Cells were protected against GA
      cytotoxicity when pretreated with increasing levels of superoxide
      dismutase/catalase mixture, NAC, or GSH for 3 h. The number of apoptotic cells
      increased with GA dose. GA caused mitochondrial potential loss, cytochrome c
      release, and activation of caspases 3, 8 and 9. CONCLUSION: The ROS-dependent
      apoptotic mechanism of GA kills malignant cells effectively; it is likely that GA
      could be a good anticancer agent.

PMID- 22593438
TI  - Effect of miR-34b overexpression on the radiosensitivity of non-small cell lung
      cancer cell lines.
AB  - BACKGROUND: The miR-34 family, under-expressed in-non small cell lung cancers
      (NSCLCs), are effectors of p53 activation upon irradiation of cells. We evaluated
      whether the miR-34b overexpression modulates the NSCLCs response to radiation.
      MATERIALS AND METHODS: NSCLC cell lines A549 with V-KI-RAS2 Kirsten Rat Sarcoma
      viral oncogene (KRAS) codon 12 mutation and with wild type p53, and H1299, not
      expressing p53, were irradiated after transfection with pre-miR-34b. Cell
      survival was assessed by clonogenic survival assays. The apoptosis and the cell
      cycle were evaluated by flow cytometry. RESULTS: In the A549 cell line,
      overexpression of miR-34b significantly reduced cell survival at lower than 4 Gy
      radiation doses. There was a significant reduction in B-cell CLL/lymphoma 2
      (BCL2) expression but no significant differences were observed in the apoptotic
      cell population or the cycle profile. No significant effect was recorded in the
      H1299 irradiated cells. CONCLUSION: In the p53 wild type, KRAS mutated NSCLC
      cells, the overexpression of miR-34b increases radiosensitivity at low doses of
      radiation.

PMID- 22593439
TI  - Broad spectrum preclinical antitumor activity of eribulin (Halaven(R)): optimal
      effectiveness under intermittent dosing conditions.
AB  - BACKGROUND: Eribulin is a pharmaceutically and structurally optimized analog of
      the marine sponge natural product halichondrin B. Its salt form, eribulin
      mesylate (Halaven(r)) is clinically used in the United States, the European
      Union, and Japan for the treatment of heavily pretreated patients with metastatic
      breast cancer, who previously received an anthracycline and a taxane. Early
      preclinical studies of this new inhibitor of microtubule dynamics showed high
      antitumor potency towards several human cancer types in vitro and in vivo. Here
      we extend those early studies by examining the effects of eribulin against a
      wider spectrum of human tumor xenografts in vivo, and by directly comparing the
      in vivo effectiveness of different dosing administration schedules. MATERIALS AND
      METHODS: In single-schedule studies, in vivo activity of eribulin against HT-1080
      fibrosarcoma, U251 glioblastoma, SR-475 head and neck cancer, SK-LMS-1
      leiomyosarcoma, NCI-H322M and NCI-H522 non-small cell lung cancer (NSCLC), PANC-1
      pancreatic cancer, and NCI-H82 small cell lung cancer (SCLC) xenografts was
      examined at dose levels of 0.19-4.0 mg/kg using q2d*3(*3), q4d*3, q4d*4, and
      q7d*2 schedules. Administration schedule dependence was evaluated by directly
      comparing q1d*5, q2d*3(*3), q4d*3, and q7d*3 schedules in the MDA-MB-435 breast
      cancer xenograft model, using conditions of equivalent total dosing over the
      course of the experiment. RESULTS: In single-schedule studies, maximum tolerated
      dose (MTD) values (or maximal 'at or below MTD' values) ranged from 0.8-1.7
      mg/kg. In vivo antitumor responses at these dosing levels included tumor growth
      inhibition, stasis, and regression; several studies showing regression also
      yielded long-term tumor-free survivors. Effectiveness of eribulin showed model-to
      model variability that appeared to be unrelated to dose level or administration
      schedule, suggesting that characterization of models with differing eribulin
      sensitivities may reveal potential biomarker strategies. Results of the dose
      schedule comparison study in the MDA-MB-435 model suggested the following order
      of effectiveness and tolerability: q2d*3(*3)>q4d*3~q7d*3>> q1d*5. Moderately
      intermittent dosing thus shows optimal preclinical effectiveness, in good
      agreement with the approved intermittent clinical schedule for eribulin (days 1
      and 8 of a 21-day cycle). CONCLUSION: The current results show that eribulin has
      broad spectrum preclinical antitumor activity against a wide variety of human
      cancer types, and indicate that maximum effectiveness and optimal tolerability
      are obtained using moderately intermittent dosing schedules.

PMID- 22593440
TI  - Utility of cell-free tumour DNA for post-surgical follow-up of colorectal cancer
      patients.
AB  - BACKGROUND: While efficient surgical treatment is the key to prolonged survival
      of patients with colorectal cancer, post-surgical follow-up is important for the
      early detection of relapsing disease or of disease progression. Current
      dispensarization, typically based on imaging CT, PET, MR, is frequently supported
      by the observation of tumour markers (CEA, CA19-9). Due to their limited
      sensitivity and selectivity, better tools for monitoring of the disease are
      desirable. Tumour cell-free DNA (cfDNA) has been recently demonstrated as a new
      promising molecular marker for observation and early detection of disease
      progression. PATIENTS AND METHODS: We present results of post-surgical monitoring
      tumour cfDNA in the cases of seven patients suffering from advanced forms of CRC.
      We applied a mutation-based approach in which the total cfDNA was screened for a
      specific somatic mutation present in the primary tumour. We screened a panel of
      the most frequent somatic mutations covering the genes APC, KRAS, TP53, PIK3CA
      and BRAF. All patients were tested positive for tumour cfDNA prior to surgery.
      cfDNA was then evaluated within a week after surgery and subsequently in monthly
      intervals. RESULTS: We present typical cases of colorectal cancer patients who
      underwent surgical treatment at different levels of radicality with or without
      adjuvant chemo/biotherapy. The tumour cfDNA status was found to be always closely
      correlated with the actual clinical status of the patient. CONCLUSION: The cfDNA
      appears to be a viable tool for the monitoring of the clinical progression of CRC
      in patients with cfDNA positivity prior to surgery.

PMID- 22593441
TI  - Metformin and the mTOR inhibitor everolimus (RAD001) sensitize breast cancer
      cells to the cytotoxic effect of chemotherapeutic drugs in vitro.
AB  - AIM: Metformin appears to interfere directly with cell proliferation and
      apoptosis in cancer cells in a non-insulin-mediated manner. One of the key
      mechanisms of metformin's action is the activation of adenosine monophosphate
      activated protein kinase (AMPK). AMPK is linked with the phosphatidylinositol 3
      kinase (PI3K)/ phosphatase and tensin homolog (PTEN)/protein kinase B (AKT)
      pathway and mitogen-activated protein kinase (MAPK)/extracellular signal
      regulated kinases (ERK) cascades--all known for being frequently dysregulated in
      breast cancer. Therefore, simultaneously targeting AMPK through metformin and the
      PI3K/AKT/mTOR pathway by an mTOR inhibitor could become a therapeutic approach.
      The aim of this study was to evaluate the anticancer effect of metformin alone
      and in combination with chemotherapeutic drugs and the mTOR inhibitor RAD001.
      MATERIALS AND METHODS: The proliferation of breast cancer cells was measured with
      the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; and
      the cell apoptosis with enzyme-linked immunosorbent assay (ELISA). Gene
      expression at the protein level was determined by western blot. RESULTS: We
      tested metformin alone and in combination with RAD001 and/or chemotherapeutic
      agents (carboplatin, paclitaxel and doxorubicin, respectively) on several human
      breast cancer cell lines with respect to cell proliferation, apoptosis and
      autophagy. Metformin alone inhibited cell proliferation and induced apoptosis in
      different breast cancer cell lines (ERalpha-positive, HER2-positive, and triple
      negative). The cytotoxic effect of metformin was more remarkable in triple
      negative breast cancer cell lines than in other cell lines. The cell apoptosis
      induced by metformin is, at least partly, caspase-dependent and apoptosis
      inducing factor (AIF)-dependent. Interestingly, we demonstrated that metformin
      induced cell autophagy. Inhibiting autophagy with chloroquine, enhanced the
      treatment efficacy of metformin, indicating that autophagy induced by metformin
      may protect breast cancer cells from apoptosis. We further demonstrated that co
      administration of metformin with chemotherapeutic agents and RAD001 intensified
      the inhibition of cell proliferation. The analysis of cell cycle-regulating
      proteins cyclin D, cyclin E and p27 by western blot indicated that the
      synergistic inhibition of G1 phase of the cell cycle by the combination treatment
      of metformin, chemotherapeutic drugs and/or RAD001 contributed to the synergistic
      inhibition of cell proliferation. CONCLUSION: Our investigation provides a
      rationale for the clinical application of metformin within treatment regimens for
      breast cancer.

PMID- 22593442
TI  - EGFR and P-GP expression in oropharyngeal mucosa in relation to smoking.
AB  - BACKGROUND: About two thirds of head and neck squamous cell carcinoma (HNSCC)
      cases are attributable to heavy tobacco and alcohol consumption. Tobacco
      carcinogens cause cellular damage in large areas of the upper aerodigestive tract
      mucosa and contribute to distinct molecular changes, such as increasing levels of
      epidermal growth factor receptor (EGFR), during carcinogenesis. P-Glycoprotein (P
      GP) is a multidrug-resistance transporter protein capable of extruding not only
      cytotoxic drugs, but also certain tobacco-related carcinogens. EGFR plays a major
      role in the transcriptional and functional regulation of P-GP and previous
      studies in our laboratory showed that stimulation of EGFR protection protected
      oropharyngeal cells from a carcinogen that is substrate of P-GP. Therefore, we
      evaluated expression levels of EGFR and P-GP and looked for a possible
      association with the smoking status of patients. MATERIALS AND METHODS: Tissue
      cultures of healthy oropharyngeal mucosa were produced from 30 patients
      undergoing surgery at our Department. Expression levels of EGFR on P-GP were
      determined by immunohistochemical staining. To evaluate possible influences of
      EGFR on P-GP expression, we stimulated the receptor using transforming growth
      factor alpha (TGF-alpha) for 24, 48 and 72 h. RESULTS: Current and former smokers
      had significantly higher EGFR/P-GP levels than never smokers. While EGFR
      expression was detected in almost all samples, P-GP expression was largely
      restricted to former and current smokers. TGF-alpha had no detectable effect on
      EGFR/P-GP levels. CONCLUSION: These results show an association between tobacco
      use and levels of both proteins. Since both these proteins are involved in drug
      resistance of head and neck cancer, this study might help to further understand
      the differences in response to therapy and prognosis of tobacco-related and 
      unrelated cancer.

PMID- 22593443
TI  - Acquisition of anoikis resistance up-regulates caveolin-1 expression in human non
      small cell lung cancer cells.
AB  - BACKGROUND: Anoikis is a key inhibitory step in the process of cancer cell
      metastasis. Knowledge regarding the adaptive response resulting in resistance to
      anoikis may benefit the development of new therapies. MATERIALS AND METHODS:
      Anoikis-resistant cells were generated from anoikis-sensitive lung carcinoma
      cells and the underlying mechanism for this process was investigated. RESULTS:
      Culturing H460 cells under suspended conditions caused spontaneous generation of
      anoikis-resistant H_AR1 and H_AR2 cells. We found that anoikis resistance in
      these cells caused caveolin-1 (CAV1) up-regulation. Using short hairpin RNA
      (shRNA), we confirmed that depletion of CAV1 rendered anoikis-resistant H_AR2
      cells sensitive to anoikis. Furthermore, this study revealed that the acquisition
      of anoikis resistance induced CAV1 up-regulation through induction of CAV1 mRNA
      transcription. CONCLUSION: Our findings show CAV1 to be a key player in anoikis
      resistance and provide a novel mechanism regarding cancer cell adaptation,
      resulting in acquisition of anoikis resistance in lung cancer cells.

PMID- 22593444
TI  - Sub-toxic cisplatin mediates anoikis resistance through hydrogen peroxide-induced
      caveolin-1 up-regulation in non-small cell lung cancer cells.
AB  - BACKGROUND: Exposure to inadequate chemotherapy may alter cancer cell behavior
      including their metastatic potential. Because the molecular basis of such a
      phenomenon is largely unclear, we investigated the possible impact of cisplatin
      on anoikis response on human lung carcinoma cells. MATERIALS AND METHODS: Using
      molecular and pharmacological tools, Caveolin-1 (CAV1) overexpressing and knock
      down H460 cells were generated by stable transfection. The levels of CAV1 were
      determined by western blotting and reactive oxygen species (ROS) were detected by
      specific probes. RESULTS: Sub-toxic concentrations of cisplatin suppressed
      anoikis response in H460 cells. The anoikis attenuation observed, was found to be
      caused by CAV1 up-regulation. Exposure to cisplatin induced superoxide anion and
      hydrogen peroxide generation; however, only hydrogen peroxide was found to be
      responsible for the CAV1 elevation. CONCLUSION: Exposure to cisplatin at sub
      toxic concentrations induced hydrogen peroxide generation and the subsequent
      increase of ROS further regulated CAV1 levels and anoikis resistance. Our
      findings demonstrate a novel effect of cisplatin treatment on cancer cells which
      may lead to a better understanding of cancer biology and in the improvement of
      chemotherapy.

PMID- 22593445
TI  - Safrole induces G0/G1 phase arrest via inhibition of cyclin E and provokes
      apoptosis through endoplasmic reticulum stress and mitochondrion-dependent
      pathways in human leukemia HL-60 cells.
AB  - Safrole, a component of Piper betle inflorescence, is a carcinogen which has been
      demonstrated to induce apoptosis on human oral cancer HSC-3 cells in vitro and to
      inhibit HSC-3 cells in xenograft tumor cells in vivo. In our previous study,
      safrole promoted phagocytosis by macrophages and natural killer cell cytotoxicity
      in normal BALB/c mice. The cytotoxic effects of safrole on HL-60 cells were
      investigated by using flow cytometric analysis, comet assay, 4',6-diamidino-2
      phenylindole (DAPI) staining, western blotting and confocal laser microscopy. The
      obtained results indicate that safrole induced a cytotoxic response through
      reducing the percentage of viable cells and induction of apoptosis in HL-60 cells
      in a dose-dependent manner. DAPI staining and comet assay also showed that
      safrole induced apoptosis (chromatin condensation) and DNA damage in HL-60 cells.
      The flow cytometric assay showed that safrole increased the production of
      reactive oxygen species (ROS) and Ca(2+) and reduced the mitochondrial membrane
      potential in HL-60 cells. Safrole enhanced the levels of the pro-apoptotic
      protein BAX, inhibited those of the anti-apoptotic protein BCL-2 and promoted the
      levels of apoptosis-inducing factor (AIF) and endonuclease G (Endo G) in HL-60
      cells. Furthermore, safrole promoted the expression of glucose-regulated protein
      78 (GRP78), growth arrest- and DNA damage-inducible gene 153 (GADD153) and of
      activating transcription factor 6alpha (ATF-6alpha). Based on these findings, we
      suggest that safrole-induced apoptosis in HL-60 cells is mediated through the ER
      stress and intrinsic signaling pathways.

PMID- 22593446
TI  - The survivin suppressant YM155 potentiates chemosensitivity to gemcitabine in the
      human pancreatic cancer cell line MiaPaCa-2.
AB  - BACKGROUND: Survivin is a negative regulator of apoptosis. We evaluated the
      efficacy of YM155, a selective suppressant of survivin, in combination with
      gemcitabine in the pancreatic cancer cell line MiaPaCa-2. MATERIALS AND METHODS:
      Expression of survivin was demonstrated by immunoblotting. Cell cycle progression
      was determined by flow cytometric analysis. Cell viability was assayed using the
      trypan blue exclusion assay. RESULTS: Gemcitabine up-regulated survivin
      expression, whereas treatment with YM155 suppressed the expression of survivin.
      Concomitant treatment with YM155 enhanced chemosensitivity to gemcitabine, which
      was accompanied by a decrease in the expression of survivin. Knockdown of
      endogenous survivin via RNA interference also enhanced the sensitivity to
      gemcitabine. In addition, YM155 potentiated the antitumor effect of gemcitabine
      in xenograft tumors of MiaPaCa-2. CONCLUSION: YM155 potentiates chemosensitivity
      to gemcitabine in pancreatic cancer cells by suppressing the induction of
      survivin. Combination treatment with gemcitabine and YM155 may be a potential
      therapeutic strategy for the treatment of pancreatic cancer that warrants further
      clinical investigation.

PMID- 22593447
TI  - A phase I study to determine the safety and pharmacokinetics of intravenous
      administration of TAS-106 once per week for three consecutive weeks every 28 days
      in patients with solid tumors.
AB  - BACKGROUND: The nucleoside 3'-c-ethynylcytidine (TAS-106) was designed to inhibit
      RNA synthesis which occurs throughout the cell cycle except for the M phase. TAS
      106 is incorporated into cells, is rapidly phosphorylated to a monophosphate
      form, and is preferentially distributed into malignant cells. Preclinical studies
      showed that TAS-106 has a wide antitumor spectrum against human cancer
      xenografts. This phase I study was conducted in order to determine the
      recommended phase II dose of TAS-106 administered once per week for three
      consecutive weeks, every 28 days in patients with solid tumors. PATIENTS AND
      METHODS: Patients were enrolled in cohorts of three, starting at 0.22
      mg/m(2)/dose. Patients received at least two doses in order to be evaluable in
      each dose cohort. Dose escalation was stopped if two or more patients experienced
      dose limiting toxicity at any dose level. RESULTS: In 20 evaluable patients, TAS
      106 was given at the following dose levels (mg/m(2)/dose): 0.22 (3 pts), 0.33 (3
      pts), 0.66 (3 pts), 0.99 (1 pt), 1.32 (3 pts), 2.64 (3 pts) and 3.96 (1 pt).
      Three additional patients were evaluated at 2.64 mg/m(2)/dose for further
      characterization of toxicity and safety. A total of 16 patients completed courses
      1 and 2. All 21 patients enrolled experienced at least one adverse event. The AE
      attributed to the study drug was grade 2 peripheral neuropathy characterized by
      peripheral sensory neuropathy, numbness, tremor, pain, and hyperesthesia
      involving the fingers, hands, toes, and feet. CONCLUSION: Due to neurotoxicity
      the MTD was the 2.64 mg/m(2)/dose for the study schedule. No suggested phase II
      dose was determined. However, at the 1.32 mg/m(2)/dose level, no patients
      experienced DLTs during course 1 or 2. This could be further studied to determine
      its viability as a potential phase II dosage.

PMID- 22593448
TI  - Olfactory neuroblastoma: 15 years of experience.
AB  - BACKGROUND: Olfactory neuroblastoma is a rare malignant neoplasm of the nasal
      cavity and of the paranasal sinus. In the treatment of patients with advanced
      olfactory neuroblastoma, the combination of craniofacial resection with
      radiotherapy and/or chemotherapy has significantly improved the survival rate.
      However, locoregional recurrence and distant metastasis frequently occur,
      irrespective of the aggressiveness of therapy. We report our experience on the
      outcomes of olfactory neuroblastoma in patients treated with concurrent
      chemoradiotherapy (CCRT). PATIENTS AND METHODS: We retrospectively analyzed the
      cases of seven patients with olfactory neuroblastoma, treated in the past 15
      years. Six patients were treated with CCRT, consisting of cisplatin (60 mg/m(2),
      day 4), 5-fluorouracil (600 mg/m(2), given over 24 h for 5 days, days 1-5),
      methotrexate (30 mg/m(2), day 1) and leucovorin (20 mg/m(2), days 1-5) (PFML).
      One patient was treated with radiotherapy and neoadjuvant chemotherapy, which
      consisted of a combination of three drugs: cyclophosphamide (360 mg/m(2), day 1),
      cisplatin (60 mg/m(2), day 4), 5-fluorouracil (600 mg/m(2), given over 24 h for 5
      days, days 1-5) (PFC). Salvage surgery was performed in the primary remaining
      site. RESULTS: The overall 5-year survival rates were 3/6 for patients treated
      with CCRT using PFML and 2/5 for patients with Kadish stage C olfactory
      neuroblastoma. The locoregional response rate was 4/6. CONCLUSION: In our limited
      experience, CCRT with PFML had therapeutic efficacy as a primary treatment, while
      surgical treatment and postoperative radiotherapy have been the main treatment
      modalities.

PMID- 22593449
TI  - Utility of insulin-like growth factor receptor-1 expression in gefitinib-treated
      patients with non-small cell lung cancer.
AB  - BACKGROUND: Insulin-like growth factor receptor 1 (IGF1R) is a proposed mechanism
      of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase
      inhibitors. Newer agents targeting this pathway make it of clinical interest.
      This study evaluates the IGF1R expression in regard to outcomes and molecular
      markers of EGFR activity in lung cancer patients treated with gefitinib.
      MATERIALS AND METHODS: Gefitinib-treated patients with sufficient archived tissue
      were included. The IGF1R activity was measured by immunohistochemistry and the
      EGFR by immunohistochemistry, fluorescent in situ hybridization, and gene
      mutation testing. Logistic regression and cox proportional hazards models were
      used. RESULTS: A total of 83 patients were included in the study: 71% were
      positive for IGF1R expression which was not associated with EGFR parameters or
      clinical outcomes. Exploratory analyses showed counter-intuitive improved
      outcomes with co-expression of IGF1R and EGFR. CONCLUSION: IGF1R expression
      measured by immunohistochemistry does not appear to be related to gefitinib
      resistance.

PMID- 22593450
TI  - Classification of gastritis in first-degree relatives of patients with gastric
      cancer in a high cancer-risk area in Italy.
AB  - BACKGROUND: Screening gastroscopic examinations were performed in a cohort of
      individuals at high risk for developing gastric carcinoma (GC). PATIENTS AND
      METHODS: Five gastric biopsies were obtained following the Houston schema. Five
      histological parameters of gastritis were investigated: acute gastritis, chronic
      gastritis, and its sequelae; mucosal atrophy, intestinal metaplasia and
      pseudopyloric metaplasia. RESULTS: Out of 134 patients, 50% (n=67) had
      Helicobacter pylori (HP) infection. The sum of scores for the first four
      parameters was significantly higher in HP-positive cases than in HP-negative ones
      (p<0.0001). The frequency of these histological parameters was similar to other
      series from Northern and Central Italy. Hence, none of the histological
      parameters of gastritis explain the high GC risk in this borough of Florence,
      considering that the incidence rate of GC is higher in Central than in Northern
      Italy. CONCLUSION: Similarities in the frequency of chronic gastritis and
      sequelae in Northern and Central Italy substantiate the conviction that the
      difference in GC risk in these regions might be the result of local environmental
      or lifestyle factors, rather than HP infection. This knowledge is crucial,
      considering that environmentally related diseases are theoretically preventable.

PMID- 22593451
TI  - Metastasis to the penis from rectal adenocarcinoma.
AB  - Penile cancer is a serious but largely under-represented phenomenon in many of
      the large national cancer databases. Even more rare is the presentation of
      solitary metastasis to the penis from a gastrointestinal primary site. This case
      describes one such case of metastasis of rectal adenocarcinoma and details the
      patient's treatment modalities. Ultimately, although the precise etiology of this
      particular manifestation is not well understood, the prognosis is poor in the
      small group that it affects. No individual treatment has been proven superior
      with regard to long term survival.

PMID- 22593452
TI  - Oncological short-term effects and adverse events of MRI-guided selective
      neoadjuvant radiochemotherapy for rectal cancer.
AB  - AIM: To investigate the oncological short-term effects and acute side-effects of
      magnetic resonance imaging (MRI)-guided selective neoadjuvant radiochemotherapy
      (nRCT) for rectal cancer. PATIENTS AND METHODS: In a prospective multicenter
      cohort study of 230 patients with rectal cancer stage II or III, nRCT was applied
      in the following situations (n=96) only: cT4 tumors, cT3 tumors of the distal
      rectum or tumors leaving a circumferential resection margin (CRM) of <=1 mm
      between the tumor and the mesorectal fascia (mrCRM+). Pre-therapeutical tumor
      stage and involvement of mesorectal fascia were assessed by MRI and were compared
      with the pathological findings of the rectal specimens. Furthermore, tumor
      regression grades, acute side-effects, and surgical complications were analysed.
      RESULTS: Using selective nRCT, 62 out of 72 patients (86%) with mrCRM+ had tumor
      negative pathological CRM. Reduction of T category was observed in 62% and of N
      category in 88% of patients. Lymph node metastasis was found by pathology in only
      21% of all irradiated patients. Histologically complete tumor regression
      (ypT0ypN0) was observed in 15% and intermediate regression (more than 25%, but
      not complete) in 67% of patients. Fifteen percent of patients suffered from grade
      3 toxicity, but no grade 4 toxicity occurred. nRCT did not adversely influence
      surgical morbidity. CONCLUSION: Despite the negative selection of locally
      advanced rectal cancer cases for nRCT, impressive rates of tumor down-staging and
      eradication of tumor from the mesorectal fascia were achieved. The rate of
      complete regression is comparable to that in the literature. Moreover, the
      selective use of nRCT spared a considerable percentage of patients with stage
      II/III rectal cancer severe irradiation toxicity.

PMID- 22593453
TI  - Presurgical treatment with sunitinib for renal cell carcinoma with a level III/IV
      vena cava tumour thrombus.
AB  - AIM: The feasibility and safety of a presurgical treatment approach with
      sunitinib for renal cell carcinoma (RCC) with level III/IV tumour thrombus in the
      inferior vena cava (IVC) were to be evaluated and its potential ability to reduce
      the surgical morbidity explored. PATIENTS AND METHODS: In our institution, we
      treated five consecutive patients with suspected RCC and a level III/IV IVC
      tumour thrombus with preoperative sunitinib (50 mg, 4 weeks on, 2 weeks off).
      Side dose effects were assessed and the effect on the tumour size and the
      dependent surgical approach documented with a computed tomographic scan before
      and after the treatment. The data were analyzed retrospectively. RESULTS: The
      overall tolerability to presurgical sunitinib was good. All procedures were
      carried out without perioperative complications. In four patients, a reduction in
      tumour size was observed, which resulted in avoidance of a bicavital surgical
      approach with cardiopulmonary bypass in one patient. This patient was diagnosed
      with papillary renal cancer; the other four patients had clear cell carcinomas.
      CONCLUSION: Presurgical treatment with sunitinib is able to ease surgery for RCC
      tumour thrombi regardless of the histological subtype in selected patients. In
      our series, surgery was possible without additional morbidity. Two courses of a
      presurgical therapy with sunitinib seems to be an appropriate duration. In
      accordance with previously published data, presurgical sunitinib treatment may
      become more widely used in RCC with level III/IV IVC tumour thrombi but
      administered with restraint in cases of level I/II thrombi. The effects on the
      risk of recurrence and survival remain to be evaluated prospectively.

PMID- 22593454
TI  - Vaginal fistula in a patient with relapsed ovarian cancer and amelanotic
      melanoma.
AB  - BACKGROUND: Malignant vaginal melanoma is extremely rare and accounts for fewer
      than 0.3% of all melanomas in women. Amelanotic malignant melanoma is a subtype
      of melanoma with little or no pigment on visual inspection. The simultaneous
      occurrence of amelanotic melanoma of the vagina and serous ovarian cancer is
      extremely rare. CASE REPORT: A 61-year-old patient was referred to our hospital
      with recurrent ovarian cancer in association with a vaginorectal fistula. The
      first diagnosis was performed in 2009. The patient underwent multi-ovarian cancer
      recurrences after the primary cytoreductive surgery, especially in the vaginal
      vault, with several different lines of chemotherapy. The pathological results on
      this occasion demonstrated recurrent ovarian cancer with a component of
      amelanotic melanoma in the region of a vaginorectal fistula. CONCLUSION: We
      recommend detailed immunohistochemical staining, especially for recurrent ovarian
      cancer in combination with abnormal localizations or manifestations, in order to
      reveal any associations with another tumor.

PMID- 22593455
TI  - Survival of a patient with anaplastic thyroid cancer following intensity
      modulated radiotherapy and sunitinib--a case report.
AB  - BACKGROUND: Anaplastic thyroid cancer has a very poor prognosis, especially in
      patients who have gross residual disease following resection. CASE REPORT: We
      present the case of a patient with anaplastic thyroid cancer and a significant
      gross residual disease treated with intensity-modulated radiotherapy with
      concurrent chemotherapy and sunitinib who had a complete response and remains
      without evidence of disease more than 18 months after diagnosis. CONCLUSION:
      Chemoradiotherapy has an important role in the adjuvant treatment of anaplastic
      thyroid cancer in selected patients and should be considered when gross residual
      disease is present following resection. The combined use of radiotherapy and
      targeted biological agents such as sunitinib may warrant further investigation.

PMID- 22593456
TI  - Decrease of CD44-positive cells correlates with tumor response to chemotherapy in
      patients with gastrointestinal cancer.
AB  - BACKGROUND/AIM: CD44 is a multistructural and multifunctional cell surface
      molecule which is involved in cell proliferation, differentiation, migration and
      angiogenesis. Here we investigated the potential role of CD44 in patients with
      metastasized pancreatic ductal adenocarcinoma, colorectal and stomach cancer,
      which were treated with different combinations of palliative chemotherapy.
      PATIENTS AND METHODS: CD44 expression was measured by flow cytometry in patients'
      (n=15) blood samples and the findings were correlated with CA19-9 expression and
      with computed tomography results. RESULTS: We found a significant correlation
      (p<0.05) between the CD44 decrease and the tumor response according to the tumor
      marker elevation/ response evaluation criteria in solid tumors. CONCLUSION: We
      were able to monitor changes of CD44 expression after chemotherapy and detected a
      correlation between the CD44 decrease and the patients' response to treatment.
      Our findings show that CD44 detection helps to monitor chemotherapy response in
      patients with gastrointestinal cancer.

PMID- 22593457
TI  - Expression levels of thymidylate synthase, dihydropyrimidine dehydrogenase, and
      thymidine phosphorylase in patients with colorectal cancer.
AB  - BACKGROUND: Predictors of the response of colorectal cancer to chemotherapy
      remain poorly understood. We analyzed the mRNA expression levels of enzymes
      related to sensitivity to 5-fluorouracil derivatives in patients with colorectal
      cancer. PATIENTS AND METHODS: Danenberg tumor profile method (DTP) was used in
      order to measure mRNA expression levels of thymidylate synthase (TYMS),
      dihydropyrimidine dehydrogenase (DPYD), and thymidine phosphorylase (TYMP) from
      180 patients with colorectal cancer. The relations of expression levels with
      clinicopathological factors and outcomes were studied. RESULTS: Higher TYMS
      expression was associated with greater age, DPYD expression with greater age,
      poorer differentiation and low invasion, and TYMP expression with poorer
      differentiation and lack of peritoneal metastasis. DPYD expression positively
      correlated with TYMP expression. In patients with stage IV disease, high DPYD or
      TYMP expression was associated with poor outcomes. CONCLUSION: mRNA expression of
      TYMS, DPYD, and TYMP is associated with distinct characteristics and may be
      useful for predicting survival in patients with stage IV colorectal cancer.

PMID- 22593458
TI  - The relationship between antitumor effects and relative dose intensity of S-1
      plus cisplatin treatment for metastatic gastric cancer.
AB  - BACKGROUND/AIM: S-1 plus cisplatin is the standard first-line chemotherapy for
      metastatic gastric cancer (MGC) in Japan, but the relationship between dose
      intensity and antitumor effects remains unclear. PATIENTS AND METHODS: We
      retrospectively studied 64 patients who received S-1 plus cisplatin for MGC from
      January 2006 to December 2010 in two Japanese hospitals. RESULTS: The median
      relative dose intensity (RDI) of S-1 plus cisplatin was 87% (range, 59.5%-100%).
      The cut-off value of RDI of S-1 plus cisplatin was identified to be 80% by a
      receiver operating characteristic analysis of the tumor response. In the RDI<80%
      (n=19) and the RDI>=80% (n=45) groups, the response rates were 20.0% and 37.5%
      (p=0.182), the median survival times were 394 and 376 days (p=0.915), and the
      median progression-free survival (PFS) was 188 and 170 days (p=0.851),
      respectively. CONCLUSION: An appropriate RDI reduction may be permitted for
      patients with MGC in palliative settings.

PMID- 22593459
TI  - Serum pharmacokinetics in patients treated with transarterial chemoembolization
      (TACE) using two types of epirubicin-loaded microspheres.
AB  - AIM: The purpose of this study was the pharmacokinetic (PK) profile assessment in
      the serum of patients affected by hepatocellular carcinoma (HCC) treated with
      transarterial chemoembolization (TACE) with drug-eluting beads. PATIENTS AND
      METHODS: This study included 20 patients, 12 treated with DC Bead(r) and 8 with
      HepaSphere Microsphere(r), preloaded with epirubicin. No patient randomization
      was used for the inclusion in one group or in the other. Peripheral blood samples
      were obtained from all patients after the treatment, until 24 hours past the
      procedure. RESULTS: The pharmacokinetic study showed low peak serum epirubicin
      concentrations with greater drug exposure for the DC Bead(r) group (p<0.05). The
      highest drug concentration after microsphere injection was observed at 5 minutes
      in all 20 patients. In the time interval between 1 and 24 hours after TACE,
      persisting levels of epirubicin were detected in peripheral blood samples.
      CONCLUSION: A persistent and sustained drug elution for both types of
      microparticles was found.

PMID- 22593460
TI  - A KIT-negative, DOG1-positive epithelioid GIST of the stomach harboring a novel
      PDGFRA exon 14 single nucleotide deletion.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common primary mesenchymal
      tumors of the gastrointestinal tract, and most of them harbor KIT or platelet
      derived growth factor receptor alpha (PDGFRA) gain-of-function mutations. Proper
      diagnostic assessment of GISTs has become very important since the availability
      of the molecular-targeted therapy with imatinib mesylate. Histopathology remains
      the gold standard in GIST diagnosis, and immunohistochemistry plays the major
      confirmatory role. Moreover, genetic sequencing not only further confirms the
      diagnosis of GIST, but also provides information for the optimal treatment of
      patients. Herein, we describe a gastric GIST harboring a novel PDGFRA exon 14
      frameshift mutation caused by a single-nucleotide deletion. The case reported
      here represents further evidence regarding the existence of a distinct subset of
      GISTs characterized by the PDGFRA mutation, the gastric localisation, the
      epithelioid morphology, and the weak or negative immunohistochemical expression
      of KIT. DOG1 is emerging as a promising biomarker for this subgroup of GISTs.

PMID- 22593461
TI  - T315I mutation in Ph-positive acute lymphoblastic leukemia is associated with a
      highly aggressive disease phenotype: three case reports.
AB  - T315I mutation in BCR-ABL causes resistance to therapy with tyrosine kinase
      inhibitors (TKIs) in Philadelphia chromosome-positive acute lymphoblastic
      leukemia (Ph(+) ALL) cases. We report three cases of relapse accompanied by T315I
      mutation during rapid disease progression. Case 1 was a 64-year-old male. During
      chemotherapy, qPCR detected a decrease of BCR-ABL to 190 copies once, but this
      suddenly increased to 22,000 copies. The patient received dasatinib, but the
      disease relapsed hematologically when the T315I mutation was detected.
      Retrospective analysis revealed that the T315I mutated clone already existed at
      the molecular relapse occurrence. Case 2 was a 25-year-old male. The patient
      underwent bone marrow transplantation (BMT) at the first molecular complete
      remission (CR), but 102 days after BMT, the ALL relapsed at the molecular level.
      Although he received imatinib, ALL immediately fully relapsed; the T315I mutation
      was detected. Case 3 was a 40-year-old female. Molecular CR was achieved by
      induction therapy, but ALL relapsed at the molecular level (9,200 copies). The
      patient received dasatinib, but relapsed hematologically, and the T315I mutation
      was observed. She underwent umbilical cord blood transplantation, but relapsed.
      In these three cases, survival from the time of the T315I mutation detection was
      4, 2, and 6 months, respectively. The T315I mutation in Ph(+) ALL was associated
      with a highly aggressive disease phenotype. In order to make appropriate
      therapeutic decisions, it is important to analyze the mutations immediately at
      the time of molecular relapse.

PMID- 22593462
TI  - Airway stenting for malignant respiratory complications in esophageal cancer.
AB  - Airway stenting is required for the palliative treatment of advanced esophageal
      cancer. This study retrospectively analyzes the outcomes of airway stenting for
      esophageal cancer at our institution. Data from nine patients who underwent
      airway stenting were reviewed. All patients had poor respiratory status due to
      esophagorespiratory fistula and/or respiratory stenosis. We retrospectively
      assessed the results of airway stenting as five grades of respiratory symptoms,
      regarding stent-related complications and clinical course and survival. Six
      silicone and six covered self-expandable metallic stents were deployed in five
      and six patients, respectively. Two types of airway stents were deployed in two
      patients, and double stents were positioned in the airway and in the esophagus of
      three other patients. The grade of respiratory symptoms improved in seven
      patients. The mean dyspnea grade was 3.0+/-0.9 and 1.3+/-1.3 before and after
      airway stenting, respectively. Stent-related complications comprised of chest
      pain, incomplete closure of the ERF, sputum retention and stent migration. The
      mean+/-SD survival of all patients was 103+/-108 (range, 0 to 325) days, and the
      survival of patients without relapsed cancer at the time of stenting, who
      underwent cancer-specific therapy after stenting, was prolonged. Although the
      airway should be stented according to the status and the prognosis of each
      patient individually stenting can relieve symptoms and improve the prognosis even
      when esophageal cancer is at very advanced stages. Airway stenting could play a
      role in the multidisciplinary management of advanced esophageal cancer.

PMID- 22593463
TI  - The interplay between hemostasis and malignancy: the oral cancer paradigm.
AB  - Accumulating evidence has revealed the role of various components of the
      coagulatory system in different stages of carcinogenesis including precancerous
      and initial stages, tumor growth, angiogenesis, stroma generation, and metastasis
      of malignant cells. This comprehensive review discusses major points of evidence,
      in addition to recent findings on specific factors associated with the paradigm
      of oral squamous cell carcinoma. During carcinogenesis, angiogenesis is favored
      by local conditions of hypoxia, cell-to-cell interactions, and by expression of
      paracrine growth factors and inflammatory cytokines. In the oral region
      specifically, genetic association studies have revealed that constitutively high
      gene expression of certain inflammatory cytokines plays a major role in
      carcinogenesis. Tissue factor (TF) has a physiological role in hemostasis, but it
      also constitutes a notable procoagulant in many types of cancer, since it appears
      to be constitutively expressed by tumor cells. Furthermore, its pathway regulates
      mechanisms which involve plasmin and matrix metallo-proteinases, both of which
      seem to be critical in oral carcinogenesis. Thrombin has a central role in
      hemostasis but it may also promote angiogenesis through pathways independently of
      fibrin generation. Thrombomodulin may act through attenuation of the tumor
      promoting properties of thrombin, but it also may function as a cell-to-cell
      adhesion molecule, independently of its anticoagulant action. The activation of
      fibrinogen by thrombin and its cleavage to fibrin monomers result in the rapid
      formation of fibrin matrix. Furthermore, it is well documented that fibrinogen
      and cross-linked fibrin reside inside the tumor stroma, facilitating its
      remodeling, angiogenesis, tumor growth and metastasis. In conclusion, the
      hemostatic system contributes to the development of the malignant phenotype
      acting on many different levels.

PMID- 22593464
TI  - Serum amyloid A: a biomarker for renal cancer.
AB  - BACKGROUND/AIM: Serum amyloid A (SAA) has been identified as a potential
      biomarker for renal cell carcinoma. We examined its diagnostic value in patients
      of different tumor stages. PATIENTS AND METHODS: In our study, 48 patients with
      localized and 67 patients with advanced renal tumors were included. 24 patients
      served as a control group. Interleukine 6 (IL-6), C-reactive protein (CRP) and
      SAA levels were measured preoperatively and at day 5 after nephrectomy. RESULTS:
      The IL-6, CRP and SAA levels in patients with advanced tumors are significantly
      higher than those of patients with localized tumors. Advanced tumors were
      identified with a sensitivity of 78% (SAA), 69% (CRP) and 44% (IL-6). The
      specificity was 82%, 82% and 94% for SAA, CRP and IL-6, respectively. CONCLUSION:
      Our results indicate that advanced renal cancers are accompanied by increased
      levels of acute-phase proteins such as CRP and SAA. SAA is found to be more
      sensitive than CRP for the indication of advanced renal cancer.

PMID- 22593465
TI  - Pilot study of duloxetine for cancer patients with neuropathic pain non
      responsive to pregabalin.
AB  - BACKGROUND: Neuropathic pain frequently occurs in cancer patients, but no drug
      therapy has been established for this type of disorder. The purpose of this study
      was to investigate the effect of duloxetine in cancer patients suffering from
      neuropathic pain. PATIENTS AND METHODS: The subjects of the study were 15 cancer
      patients with neuropathic pain who visited the Kinki University Faculty of
      Medicine Hospital and met the International Association for the Study of Pain
      diagnostic criteria for neuropathic pain. Duloxetine was administered to patients
      in whom pregabalin could not be administered. The influence of duloxetine was
      investigated retrospectively with the use of a numerical rating scale. RESULTS:
      Pain was reduced in 7 out of the 15 patients. Sleepiness and the light-headed
      feeling were improved in four patients, in whom, however, the pain was not
      reduced. Thus, duloxetine was judged to be effective in 11 patients. The
      maintenance dose of duloxetine was 20-40 mg/day. CONCLUSION: Duloxetine
      administration may be effective for neuropathic pain in cancer patients who
      cannot tolerate pregabalin administration.

PMID- 22593466
TI  - Prognostic factors and clinical outcome of patients with lung adenocarcinoma with
      carcinomatous meningitis.
AB  - BACKGROUND: In recent years, the incidence of carcinomatous meningitis (CM) in
      lung adenocarcinoma has been rising. However, it remains unclear which treatment
      strategies improve the outcome of these patients. PATIENTS AND METHODS: We
      retrospectively reviewed data for 67 lung adenocarcinoma patients diagnosed with
      CM between September 2002 and March 2011 in order to identify factors which would
      improve prognosis. RESULTS: In multivariate analysis, the female gender, a good
      performance status (PS) 0-2 and the mutant epidermal growth factor receptor
      (EGFR) gene were identified as factors associated with a favorable prognosis. The
      survival time was significantly prolonged for patients treated with EGFR-tyrosine
      kinase inhibitors (TKIs) (240 vs. 57 days, p<0.0001) and for patients who
      underwent radiotherapy of the central nervous system (CNS) (201 vs. 76 days,
      p=0.0038) after diagnosis of CM. The median survival time (MST) of patients
      treated with gefitinib before diagnosis of CM and with erlotinib after diagnosis
      was significantly longer than the MST of patients treated with gefitinib both
      before and after the diagnosis of CM (407 vs. 205 days, p=0.0015). Patients
      treated with both radiotherapy for CNS and EGFR-TKI had longer survival compared
      to patients without radiotherapy for the CNS (379 vs. 122 days, p=0.032).
      CONCLUSION: EGFR-TKI combined with radiotherapy may be a therapeutic approach
      capable of improving the prognosis of patients with lung adenocarcinoma with CM
      harboring the EGFR gene mutation.

PMID- 22593467
TI  - Patient age and biological aggressiveness of endometrial carcinoma.
AB  - BACKGROUND: Advanced age is associated with a significantly worse prognosis of
      endometrial carcinoma patients. The aim of this study was to test whether age is
      a poor-risk factor in endometrial carcinoma because tumors arising in older
      patients are biologically different from those diagnosed in patients of an
      earlier age. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded samples
      from 136 previously untreated patients with endometrial carcinoma were studied by
      means of immunohistochemistry. The expression of molecular markers associated
      with hormone responsiveness (estrogen and progesterone receptors), proliferation
      (Ki67, C-ERB-B2, p53), invasiveness (E-cadherin) and apoptosis (BCL2 and p53) was
      analyzed. The obtained expression levels, together with all available clinical
      and pathological features were tested for correlations with the patients age and
      survival. RESULTS: Advanced patient age showed a direct correlation with tumor
      stage (r=0.29, p=0.0008) and mutant p53 expression (r=0.25, p=0.004), and an
      inverse correlation with E-cadherin expression (r=-0.28, p=0.001). Patient age
      above the 25th percentile (57 years) of the age distribution was significantly
      associated with a worse prognosis (p=0.018). CONCLUSION: It appears that with
      advancing age, endometrial carcinoma exhibits a more aggressive tumor phenotype,
      characterized by mutant p53 expression and down-regulation of E-cadherin
      expression, and that this, in its turn, results in tumors being diagnosed at a
      more advanced stage in older patients.

PMID- 22593468
TI  - Treatment strategies for well-differentiated liposarcomas and therapeutic
      outcomes.
AB  - This study examined 45 patients with well-differentiated liposarcoma who were
      surgically treated at our hospital (initial surgery in 41 patients and
      reoperation in 4). Only one patient had recurrence among patients who underwent
      initial surgery, and the recurrence was localised in the retroperitoneal space.
      For patients who underwent reoperation, the mean time between the initial surgery
      and the recurrence was 16.5 years. None of the 45 patients developed distant
      metastasis. It is important to preserve not only neurovascular bundles but also
      lower limb muscles in order to maintain ambulatory ability in the elderly
      patients. For well-differentiated liposarcomas of the limbs, it is important to
      establish a surgical margin beyond the marginal resection border and to perform
      muscle resection to the extent that would not greatly reduce the muscle strength.

PMID- 22593469
TI  - A combined therapy with docetaxel and nedaplatin for relapsed and metastatic
      esophageal carcinoma.
AB  - We performed combined chemotherapy using docetaxel and nedaplatin with and
      without radiation therapy as a second-line treatment for relapsed or metastatic
      esophageal carcinoma. Eighteen patients were enrolled from April 2003 to June
      2010; 10 cases were metastatic and 8 cases were recurrent. Nedaplatin (30
      mg/m(2)) and Docetaxel (30 mg/m(2)/day) were administered on days 1, 8 and 15.
      Nine cases undertook the combined-chemotherapy only, with a response rate of
      22.2% (2/9). The other nine cases received combined chemo-radiotherapy, with a
      response rate of 55.5% (5/9). The median survival time of all patients was 273
      days, the median survival time for patients treated with combined chemotherapy
      was 331 days, while for patients treated with combined chemoradiotherapy was 244
      days. The two-year survival rate overall was 11.1% (1/9). The adverse event of
      leukocytopenia greater than grade 3 was observed in three cases of combined
      chemoradiotherapy cases only. Docetaxel and Nedaplatin combination chemotherapy
      is well tolerated and useful as second-line chemotherapy for patients with
      relapsed or metastatic esophageal cancer.

PMID- 22593470
TI  - Salvage chemotherapy with cisplatin and 5-fluorouracil in metastatic breast
      cancer. Particular activity against liver metastases.
AB  - BACKGROUND: The prognosis of patients with metastatic breast cancer who have
      failed to respond to at least two different chemotherapy regimens is poor. Such
      patients with metastatic disease to the liver have even worse prognosis.
      Cisplatin and 5-fluorouracil (5-FU) can be given in patients with impaired
      hepatic function but their combination has not been extensively studied in this
      setting. PATIENTS AND METHODS: We retrospectively collected data from our
      registry on patients with advanced metastatic breast cancer who received
      combination of cisplatin/5-FU. We sought to determine the toxicity, the response
      rate, the disease control rate and the survival of this combination. RESULTS: We
      identified 25 heavily pre-treated patients, out of which 19 (76%) had liver
      metastases. They had been treated before with a median of three lines of
      cytotoxic chemotherapy. The majority of patients had also received hormonal
      manipulation or trastuzumab. The median number of cisplatin/5-FU administered
      cycles, without toxic deaths or unexpected toxicities was four. The partial
      response (PR) rate was 32% and the disease control rate (DCR) was 68%. The time
      to progression was five months and the median survival after starting on
      cisplatin/5-FU was six months. CONCLUSION: The combination of cisplatin/5-FU is
      active and safe in heavily pre-treated patients with metastatic breast cancer
      even in the presence of liver metastases and jaundice.

PMID- 22593471
TI  - Evaluation of important prognostic clinical and pathological factors in gastric
      cancer.
AB  - BACKGROUND: Gastric cancer is the fourth cancer in incidence worldwide, with a
      high disease-related death rate. The aim of this study was to evaluate the
      importance of clinical and pathological factors for the prognosis of gastric
      cancer patients. MATERIALS AND METHODS: We analysed data from 304 consecutive
      patients. Clinical and pathological factors and the surgical resection status
      were analysed by univariate analyses, followed by investigation of important
      factors using a proportional hazard regression analysis with backward elimination
      in order to identify important independent prognostic factors. RESULTS:
      Univariate analysis revealed that age, pT, pN, M, UICC stage, grading, and
      resection status were significantly associated with survival. Multivariate
      analysis identified age, pT, pN, M, and resection status as independent
      prognostic factors. CONCLUSION: Besides age and pathological parameters, radical
      R0 resection plays an essential role in the management of gastric cancer and
      should be aimed at, even if extended resection may be necessary.

PMID- 22593474
TI  - Cytokeratin serum biomarkers in patients with colorectal cancer.
AB  - BACKGROUND: Circulating cytokeratins have shown to be important for management of
      patients with lung cancer. Here we investigated their role for differential
      diagnosis, therapy monitoring and prognosis in colorectal cancer (CRC). PATIENTS
      AND METHODS: Pretherapeutic levels of cytokeratin-19 fragments (CYFRA 21-1),
      carcino-embryonic antigen (CEA) and cancer antigen (CA) 19-9 were measured in 42
      patients with CRC, 45 with benign colorectal diseases and 51 healthy controls.
      Furthermore, courses of CYFRA 21-1, tissue polypeptide antigen (TPA), tissue
      polypeptide specific antigen (TPS), M30-antigen, CEA and CA 19-9 were analyzed in
      prospectively collected sera of 15 patients with CRC during primary chemotherapy
      and were correlated with therapy response and overall survival (OS). RESULTS:
      Similar to CEA and CA 19-9, CYFRA 21-1 was significantly elevated in serum from
      patients with CRC (median 2.1 ng/ml) as compared with healthy (1.2 ng/ml;
      p<0.0001) and benign gastrointestinal controls (1.7 ng/ml; p=0.0178) and showed
      stage dependency in CRC (p=0.0118). CYFRA 21-1 correlated with CEA in benign
      diseases and CRC but not with CA 19-9. The best discrimination between healthy
      controls and patients with CRC was achieved by combination of CYFRA 21-1 and CA
      19-9 (area under the curve; AUC=86.7%), while the combination of CEA and CA 19-9
      discriminated best between benign diseases and CRC (AUC=73.9%). In CRC patients
      during primary chemotherapy, levels of cytokeratins CYFRA 21-1, TPA, TPS, CEA and
      CA 19-9 tended to be higher in patients with poor response to therapy and with
      poor prognosis. CONCLUSION: Cytokeratins are elevated in patients with CRC and
      show some association with response to primary therapy and prognosis.

PMID- 22593475
TI  - Chromosomal rearrangements in PLAG1 of myoepithelial salivary gland tumours.
AB  - PLAG1 mutations are related to the development of pleomorphic adenomas. A
      specific aspect of PA is the histological diversity of this entity, containing
      cells with mesenchymal, epithelial and myoepithelial differentiation. Evidence
      for myoepithelial cells in PA raises the question whether the very rare entity of
      pure myoepithelial salivary gland tumours shows chromosomal translocations and
      rearrangements and whether activation of PLAG1 can be detected. MATERIALS AND
      METHODS: Fluorescence in-situ hybridisation (FISH) was established using the DNA
      probes PLAG 233, PLAG 234, PLAG 235. The probes were generated from plasmids.
      Standardization of FISH was achieved in human lymphocytes. Routinely formalin
      fixed, paraffin-embedded slices of myoepithelial salivary gland tumours were
      available for study. In some cases isolated nuclei were investigated. Isolation
      of the nuclei was performed according to Hedley. Scoring of the FISH was done
      with a Laser-scanning microscope (spot-counting: fluorescence signals/100
      cells/slice). The number of signal variants was determined. All evaluated regions
      were registered on microphotographs. RESULTS: PLAG1 was only rarely detected.
      PLAG1 is evidently not involved in the development of myoepithelial tumours. The
      proportion of 8q12-alterations in myoepithelial tumours was very low. CONCLUSION:
      PLAG1 is an insufficient marker to differentiate between benign and malignant
      myoepithelial tumours.

PMID- 22593476
TI  - Real-time cell analysis of human cancer cell lines after chemotherapy with
      functionalized magnetic nanoparticles.
AB  - BACKGROUND: Magnetic drug targeting is a new and innovative approach in cancer
      treatment. In order to avoid the adverse effects of chemotherapy, the therapeutic
      agent is linked to superparamagnetic nanoparticles which are injected into a
      tumour-supporting artery and is focused by an external magnetic field to the
      tumour region in order to provoke maximum local impact. Analysis of nanoparticles
      and chemotherapeutic substances in human cancer cell culture is necessary to
      provide respective information for in vivo applications. MATERIALS AND METHODS:
      The effect of pure mitoxantrone and mitoxantrone bound to nanoparticles was
      tested on human cancer cell lines using real-time cell analysis (RTCA) and
      lactate dehydrogenase (LDH) assays. RTCA was performed by impedance measuring.
      The impedance is expressed as the cell index (CI), which is a parameter of cell
      viability. RESULTS: RTCA showed that mitoxantrone when bound to nanoparticles was
      more toxic than the drug alone. The CI clearly decreased faster after adding the
      chemotherapeutic bound to nanoparticles than when adding the pure drug alone.
      However, in the first experiments, the particles themselves showed no toxicity at
      therapeutically relevant concentrations. These results were confirmed by LDH
      assays. CONCLUSION: The toxic effects of chemotherapeutic agents (e.g.
      mitoxantrone) on human cancer cell lines (e.g. MCF-7) can be enhanced if these
      drugs are bound to magnetic nanoparticles. These preliminary data show a
      dependency on the different application modes of RTCA. The results presented here
      are a first step for a better understanding of the effectiveness of magnetic drug
      targeting as a new and innovative cancer treatment.

PMID- 22593477
TI  - Vitamin D status and per-oral vitamin D supplementation in patients suffering
      from chronic pancreatitis and pancreatic cancer disease.
AB  - Exocrine pancreatic insufficiency due to chronic pancreatitis may result-
      depending on the degree of insufficiency--, in a decrease in serum 25
      hydroxyvitamin D (25(OH)D) level. However, the data in the literature concerning
      the rate and extent of vitamin D deficiency in pancreatic cancer with or without
      previous pancreas resection, are very rare, in particular regarding the question
      how to supplement these patients with vitamin D. In recent years, vitamin D is
      increasingly being discussed as one factor involved not only in musculo-skeletal
      diseases but also in cardiovascular and autoimmune diseases, cancer development,
      diabetes mellitus and overall mortality. PATIENTS AND METHODS: In all, 248
      ambulatory patients (n=140 patients suffering from exocrine pancreatic
      insufficiency due to chronic pancreatitis, pancreatic cancer with/without
      previous resections of the pancreas n=108 patients without pancreatic disease),
      we measured the serum 25(OH)D concentrations by the chemoluminescence method. In
      addition, in 91 of these patients (n=65 pancreatic patients, n=26 controls), we
      started supplementation with oral vitamin D in combination with dietary advice
      and adequate substitution with pancreatic enzyme preparations, followed by
      subsequent serum 25(OH)D determinations. The oral vitamin D doses varied from
      1000 IU per day over 1* 20,000 IU per week, or 2-3 times 20,000 IU per week up to
      20,000 IU per day in single patients, depending on the underlying disease and the
      estimated degree of maldigestion/malassimilation. In addition, in a pilot trial
      vitamins A and E were measured in the serum from 121 and 105 of these patients
      respectively (resp.) (HPLC method). RESULTS: Serum 25(OH)D concentrations were
      <30 ng/ml in 93% of the patients with pancreatic diseases,<20 ng/ml in 77.9%, <10
      ng/ml in 32.1% and <4 ng/ml in 9.3%. The results were comparable to those in
      patients suffering from chronic pancreatitis and those with pancreatic tumor
      disease, with or without a previous tumor resection (n=51 Whipple procedure, n=11
      left resection, n=9 total duodeno-pancreatectomy). Similar data were also found
      in the controls, only slightly higher. In contrast to the vitamin D data,
      however, determination of vitamins A and E in the serum resulted in values within
      the normal range for the majority of the patients of both groups, suggesting a
      diminished vitamin D uptake as being at least one reason to explain the low serum
      vitamin D concentrations in the patients with pancreatic diseases. Individual
      supplementation with oral vitamin D in all patients studied (n=91) resulted in an
      increase of the serum 25(OH)D concentrations into the normal range (14.2+/-5.8 up
      to 42.3+/-12 in controls, 11.9+/-7.4 up to 46.6+/-15.7 in patients with
      pancreatic diseases). The data of a subgroup of patients with continuous long
      term supplementation, however, suggest that some patients with pancreatic
      diseases may need a significantly higher vitamin D supplementation, up to 20000
      IU per day in single patients, compared to the controls. CONCLUSION: The results
      demonstrate that vitamin D deficiency is a common problem in patients suffering
      from exocrine pancreatic insufficiency from various reasons as well as in our
      controls. Apart from insufficient sun exposure, exocrine pancreatic
      insufficiency, as well as a too low vitamin D uptake with food seem to represent
      the main causes of low serum 25(OH)D. In nearly all patients, the serum 25(OH)D
      concentrations could be normalized by oral supplementation of vitamin D in the
      case of individual therapy based on routine serum controls.

PMID- 22593478
TI  - Surgery for advanced and metastatic pancreatic cancer--current state and trends.
AB  - Due to the late onset of symptoms in pancreatic cancer, patients are often
      presented with an already advanced or metastatic state of disease. Only in a
      minority of patients is a tumor resection indicated, e.g. in general tumor
      encasement of major vessels, while the presence of metastatic disease excludes
      patients from curative-intended surgery. Limitations for pancreatic resections
      have been debated and re-thought after more experience has gained over time. This
      holds true for en-bloc vascular resections, total pancreatectomies, intentional
      R2 pancreatic resections and synchronous resection of liver metastases. These
      issues are addressed in this review.

PMID- 22593479
TI  - Two-marker combinations for preoperative discrimination of benign and malignant
      ovarian masses.
AB  - BACKGROUND: When caring for patients with ovarian neoplasms, correct preoperative
      discrimination of benign and malignant disease is deemed vital. In this study, we
      tested serum biomarkers' alone and in combination, to achieve this aim. MATERIALS
      AND METHODS: We measured the concentrations of Cancer Antigen (CA)-125, CA15-3,
      CA27-29, Carcinoembryonic Antigen (CEA), CA19-9, human chorionic gonadotropin
      (hCG), Placental Protein (PP)1490, CA72-4, galectin-3, galectin-1 and Human
      epididymis protein (HE)4 in sera of 133 patients with pelvic masses by ELISA and
      correlated the results to subsequent histology. We used the area under the curve
      (AUC) of biomarkers and their combinations and calculated the 95% confidence
      intervals by using casewise resampling. RESULTS: The best single biomarkers were
      CA-125 (sensitivity and AUC) and HE4 (specificity). Combinations with HE4 and
      CA19-9 improved the predictive power of CA-125. The best discrimination was
      achieved by the combination of CA-125 and HE4, with an AUC of 0.961. CONCLUSION:
      A combination of CA-125 with HE4 could facilitate the identification of women at
      risk for ovarian cancer.

PMID- 22593480
TI  - Circulating microparticles in patients with benign and malignant ovarian tumors.
AB  - BACKGROUND: Microparticles are known to be increased in various malignancies. In
      this prospective study, microparticle levels were evaluated in patients with
      benign and malignant ovarian lesions. PATIENTS AND METHODS: Microparticles from
      platelets/megakaryocytes, activated platelets and endothelial cells, tissue
      factor exposing microparticles and D-dimer values were examined in patients with
      newly diagnosed ovarian lesions before surgery, and were correlated with tumor
      histology. RESULTS: Higher counts of CD63-positive microparticles were detected
      in patients with ovarian cancer [mean=276*10(6) (range: 64-948)/l; n=12] as
      compared to patients with benign ovarian tumors [146*10(6) (45-390)/l; n=21;
      p=0.014]. D-dimer values were also increased in patients with cancer [860 (180
      4500) ng/l versus 280 (170-2720) ng/l; p=0.001]. CONCLUSION: Elevated levels of
      CD63-positive microparticles and D-dimer reflect the procoagulant phenotype of
      these patients. However, for the discrimination between benign and malignant
      ovarian tumors, measuring preoperative levels of microparticles does not seem to
      be helpful.

PMID- 22593481
TI  - Comparative analysis of sensitivity to blood in the urine for urine-based point
      of-care assays (UBC rapid, NMP22 BladderChek and BTA-stat) in primary diagnosis
      of bladder carcinoma. Interference of blood on the results of urine-based POC
      tests.
AB  - BACKGROUND: According to guidelines, the primary diagnosis of bladder carcinoma
      is symptom oriented. This means that diagnostic testing is indicated for
      macrohaematuria, chronically recurrent microhaematuria and chronic bladder
      urgency. This study tests the suitability of three point of care (POC) test
      systems, UBC rapid, NMP22 BladderChek and BTA stat, available on the market, with
      respect to interference due to blood contamination in urine samples. MATERIALS
      AND METHODS: Urine samples were obtained from voluntary asymptomatic individuals
      without a history of bladder cancer. A specimen negative in all test systems was
      selected for further study. This sample was treated with fresh heparinized blood
      in a 1:10 ratio and then titrated in a dilution series. All the urine samples and
      their consecutive test results were photographed and a urinalysis was performed
      on each sample. RESULTS: In none of the samples of the dilution series did UBC
      rapid or NMP22 BladderChek show a false-positive result due to blood
      contamination. In contrast, with the BTA stat testing system, false-positive
      results were obtained from all samples with macrohaematuria and with densities up
      to 150 erythrocytes/MUl, indicating a suspected tumour, whereas the sample was
      actually proven to be tumour free. CONCLUSION: For the primary diagnosis of
      bladder carcinoma, neither the UBC rapid nor the NMP22 BladderChek POC test
      systems are sensitive to the presence of blood in the urine, whereas BTA stat
      consistently yields false-positive results due to cross-reactivity to
      macrohaematuria and microhaematuria up to a density of 150 erythrocytes/MUl, thus
      this system should not be employed for this examination.

PMID- 22593482
TI  - Expression of podoplanin in primary and metastatic poorly differentiated and
      undifferentiated carcinomas of the head and neck.
AB  - The invasive growth properties of head and neck carcinoma can be determined by
      proteins associated with cellular motility. Podoplanin is a recently identified
      protein associated with motility of cells. MATERIALS AND METHODS: Sixty-five
      tumour specimens of 51 patients with poorly and undifferentiated carcinomas were
      investigated for podoplanin expression. All tissues were fixed in buffered
      formalin and embedded in paraffin. RESULTS: Podoplanin expression showed a
      tendency towards a more intense staining in carcinomas with a squamous epithelia
      differentiation compared to tumours without any remnants of cellular layers.
      Podoplanin expression was very rarely seen in lymph node metastases and the
      staining was weak in these specimens. The differences of podoplanin expression
      between primary and metastatic carcinoma were highly significant (p<0.005).
      CONCLUSION: Podoplanin is expressed in primary undifferentiated carcinoma, both
      inside and outside of Waldeyer's ring. This study shows that podoplanin can be
      used as a marker of tumour invasion in poorly or undifferentiated head and neck
      carcinoma.

PMID- 22593483
TI  - Expression of different carbohydrate tumour markers and galectins 1 and 3 in
      normal squamous and malignant epithelia of the upper aaerodigestive tract.
AB  - AIM: Tumour markers hold a great relevance in the diagnosis and the follow-up
      treatment of different kinds of human carcinoma. Although head and neck cancer
      occurs frequently, there is still lack of appropriate tumour markers. Our
      investigation on the expression of sialyl Lewis A (CA19-9) in laryngeal
      carcinomas, consists of systematical analysis of oncofetal carbohydrates and of
      galectins 1 and 3 in different normal and malignant tissues of the aerodigestive
      tract. MATERIALS AND METHODS: Paraffin-embedded sections of normal tongue, vocal
      cord, larynx, pharynx and epiglottis, representing normal control tissue and
      laryngeal cancer tissue were incubated with monoclonal antibodies against sialyl
      Lewis A and X (sLeA and X), Lewis Y (LeY), the Thomsen-Friedenreich (TF) antigen
      and galectin 1 and 3 (Gal-1 and -3). A staining reaction was carried out with ABC
      peroxidase and diaminobenzidine (DAB). Tissue of breast cancer was used as a
      positive control. Mouse IgM, as isotype control antibody, was used as a negative
      control. Semi quantitative evaluation was carried out double-blinded, by two
      independent investigators, including a pathologist. RESULTS: Squamous epithelia
      of all investigated normal tissues of the aerodigestive tract show nearly the
      same pattern. Most impressive findings are the very weak expression of Gal-1 and
      the total absence of the TF antigen. Laryngeal cancer reveals high amounts of
      sLeA, Gal-1 and the TF antigen. CONCLUSION: On the basis of our findings in
      normal tissue of the aeradigestive tract, these three markers qualified as
      potential tumour markers for carcinoma of the aerodigestive tract. In particular,
      the high expression of TF in cancer tissue and its absence from the normal tissue
      is promising for its establishment as a new tumour marker in this field.

PMID- 22593484
TI  - Similar incidences of TP53 deletions in extramedullary organ infiltrations, soft
      tissue and osteolyses of patients with multiple myeloma.
AB  - BACKGROUND: Extramedullary (EM) organ impairment in patients with multiple
      myeloma (MM) is a rare event, occurring mostly during disease relapse after high
      dose chemotherapy with autologous or allogeneic stem cell transplantation. This
      manifestation is commonly associated with an unfavourable outcome. Previous
      studies suggested a correlation between the clinical course of patients with MM
      and EM and the cytogenetic findings, e.g. deletion of TP53 on 17p13. MATERIALS
      AND METHODS: We investigated patients with these rare plasma cell organ
      infiltrations (n=17) as well as bone lesions or soft tissue lesions, known to be
      a common clinical feature of MM (n=14), using a newly established method of
      fluorescence in situ hybridization in combination with cytoplasmic immunoglobulin
      staining (cIg-FISH) on paraffin-embedded sections and a specific probe for TP53
      on 17p13. RESULTS AND CONCLUSION: The incidence of del(17)(p13) was similar in
      both groups but overall it was higher when compared to published data obtained
      from bone marrow samples and material originating from osteolyses. Further
      investigations on a larger patient cohort are needed in order to confirm these
      findings.

PMID- 22593486
TI  - Scattering effects of irradiation on surroundings calculated for a small dental
      implant.
AB  - A fundamental improvement of restorative dentistry is the compensation of missing
      teeth by insertion of artificial dental roots allowing retention of dental
      prosthesis. The function of dental implants conserves a permanent perforation of
      the mucosa and upholds a non-physiological contact of bone with foreign material
      and oral micro-organisms. Occasionally head and neck cancer patients are
      scheduled to receive radiotherapy but are wearing dental implants. An earlier
      study had shown that the distribution of x-rays is noteworthily changed when
      dental implants are present in the irradiation field. New implants of smaller
      size are currently being designed that allow sufficient retention for dental
      prosthesis. The aim of this consecutive study was to calculate alterations in the
      irradiated bone caused by a foreign body, representing an implant of reduced size
      and physical qualities equivalent to titanium, using a stochastic (Monte Carlo)
      simulation. A clinical linear accelerator was simulated using BEAM/EGS4. The
      calculations showed that the presence of a dimension-reduced implant results in
      remarkable differences of the dose distribution all around the implant. Titanium
      dental implants of reduced size located in the field of irradiation were capable
      of causing significant radiation scattering. Similar to standard implants, the
      risk for dose enhancement was notably important for the bone in direct contact
      with the implant. All therapists involved in the therapy of cancer patients
      undergoing head and neck radiotherapy should consider the impact of dental
      implants on the radiation beam as a catalyst of osteoradionecrosis.

PMID- 22593485
TI  - PI3K inhibitor D-116883 is effective in in vitro models of ovarian cancer.
AB  - BACKGROUND: D-116883 (Aeterna Zentaris GmbH, Frankfurt, Germany) is an orally
      effective drug that acts via inhibition of phosphatidylinositol 3-kinase (PI3K).
      The PI3K/AKT signal transduction pathway is involved in ovarian cancer
      tumorigenesis. Phosphatase and Tensin homolog (PTEN) loss and other activating
      mutations frequently contribute to the activation of this pathway. We tested
      whether D-116883 exerts cytostatic effects in in vitro models of ovarian cancer
      and analyzed the induced programmed cell death. MATERIALS AND METHODS: We
      evaluated the potency of D-116883 in four ovarian carcinoma cell lines with
      different cellular assays. The effects of D-116883 on cell proliferation was
      analysed by crystal-violet staining and tetrazolium salt [(3-(4,5-dimethylthiazol
      2-yl)-2,5-diphenyltetrazolium bromide; MTT] assay. The capacity for anchorage
      independent growth was analyzed in two ovarian carcinoma cell lines without and
      with D-116883 addition by using the soft agar assay. Fluorescence activated cell
      sorting (FACS) cell cycle analyses were performed. Cells were incubated with
      multicaspase inhibitor benzyloxycarbonyl-val-ala-asp(OMe)-fluoromethylketone
      (zVAD) and inhibitor of necroptosis necrostatin. RESULTS: Growth inhibition
      occurred in all ovarian carcinoma cell lines studied (A2780, A2780cis, OAW42 and
      SKOV3) in a micromolar range (IC(50)<1 MUM). By using soft agar assay, a reduced
      capacity for anchorage-independent growth, a hallmark of tumor cells, caused by D
      116883 was demonstrated. Cell cycle analyses showed that D-116883 dose
      dependently increased apoptotic cells. Multicaspase inhibitor zVAD and inhibitor
      of necroptosis necrostatin did not abrogate the growth-inhibiting effect of the
      compound. CONCLUSION: PI3K inhibitor D-116883 showed substantial cytotoxic
      effects in various in vitro models of ovarian cancer. Our results make D-116883 a
      good candidate for further ovarian cancer research including in vivo experiments.

PMID- 22593487
TI  - Apoptosis-related biomarkers sFAS, MIF, ICAM-1 and PAI-1 in serum of breast
      cancer patients undergoing neoadjuvant chemotherapy.
AB  - BACKGROUND: Neoadjuvant chemotherapy improves surgical options and prognosis in
      patients with operable breast cancer. Predictive biomarkers are needed to choose
      the most effective therapy and to avoid unnecessary toxicity. PATIENTS AND
      METHODS: We analyzed the courses of apoptosis-related serum biomarkers macrophage
      migration-inhibitory factor (MIF), soluble cell death receptor sFAS, soluble
      intercellular adhesion molecule (sICAM), plasminogen activator inhibitor 1 (PAI
      1) as well as the oncological biomarkers carcino-embryonic antigen (CEA) and
      carbohydrate antigen 15-3 (CA15-3) in prospectively collected sera of 51 patients
      with locally confined breast cancer undergoing preoperative chemotherapy. As
      controls 31 healthy women, 13 patients with benign breast disease and 28 patients
      with metastasized breast cancer were included. RESULTS: sFAS, MIF, CEA and CA15-3
      showed significantly higher serum concentrations in patients with metastasized
      breast cancer than in healthy and benign controls. Additionally, sFAS and MIF
      discriminated between locally confined breast cancer and healthy controls with an
      area under the curve (AUC) in receiver operating characteristic (ROC) curves of
      73.4% and 70.7%. After neoadjuvant chemotherapy, 38 patients achieved complete
      (N=9) or partial (N=29) remission, while 13 patients had no change of disease.
      Pretherapeutic levels of MIF were considerably higher in non-responsive patients
      (p=0.082). In addition, post-therapeutic sICAM and CA15-3 levels were higher in
      patients without complete remission. CONCLUSION: Apoptosis-related biomarkers are
      valuable markers in breast cancer patients and show potential for early
      estimation of the efficiency of neoadjuvant chemotherapy.

PMID- 22593488
TI  - Methodological and preanalytical evaluation of an HMGB1 immunoassay.
AB  - BACKGROUND: Soluble high-mobility group box 1 (sHMGB1) is a promising biomarker
      for the prognosis and the monitoring of cancer and of acute diseases such as
      trauma and sepsis. MATERIALS AND METHODS: We investigated the methodological
      characteristics of an ELISA for sHMGB1 (Shino-Test, Tokyo, Japan and IBL,
      Hamburg, Germany) including intra- and inter-assay imprecision, dilution
      linearity and differences in serum and plasma materials. Furthermore, the
      influence of various preanalytical factors such as time and storage temperature
      before and after centrifugation prior to definite deep freezing, as well as
      multiple freeze-thaw cycles were tested. By the use of sera from 28 healthy
      individuals, a reference range and the dependency on patient characteristics were
      established. RESULTS: Intra-assay imprecision (coefficients of variation (CV)=1.2
      4.8%) and inter-assay imprecision (10.3-14.0%) were in an acceptable range of
      manual assays. HMGB1 levels were found to be considerably lower in EDTA plasma as
      compared to serum samples. Linearity testing yielded satisfying results with
      dilution recoveries of 100-121% (mean=112.3%). sHMGB1 results were the same when
      samples were kept at 4 degrees C and 25 degrees C after centrifugation, for up to
      7 days (recoveries 87-128%). Delay before centrifugation led to a considerable
      increase in some samples. The median values for healthy individuals was 1.3
      ng/ml, and the 95th percentile was 4.1 ng/ml. HMGB1 levels correlated inversely
      with age (R=0.33). CONCLUSION: The sHMGB1 ELISA is a robust and safe assay
      producing reliable quantitative results in sera.

PMID- 22593489
TI  - Peptidomimetic GnRH antagonist AEZS-115 inhibits the growth of ovarian and
      endometrial cancer cells.
AB  - BACKGROUND: AEZS-115 (Aeterna Zentaris GmbH, Frankfurt/M, Germany) is an orally
      active peptidomimetic antagonist of gonadotropin-releasing hormone (GnRH). In
      various tumors, an autocrine growth-promoting loop has been described for GnRH.
      The current study evaluates the antitumor activity and mechanism of action of
      AEZS-115 in models of ovarian and endometrial cancer. MATERIALS AND METHODS:
      Human A2780, Acis2780, OAW-42, Ovcar-3, SKOV-3, Hec1A and Ishikawa cells were
      analyzed for GnRH receptor expression by reverse transcription polymerase chain
      reaction (RT-PCR). These cell lines were incubated with AEZS-115 at 1, 10 and 100
      MUM for 24 h, 48 h, and 72 h and the number of viable cells was determined.
      Fluorescence activated cell sorting (FACS) cell cycle analyses were performed
      with increasing concentrations of AEZS-115. Co-treatment experiments of cancer
      cells with GnRH antagonist cetrorelix and peptidomimetic GnRH antagonist AESZ-115
      were carried out. RESULTS: A2780, Acis2780, OAW-42, Ovcar-3, SKOV-3, Hec1A and
      Ishikawa cells expressed GnRH receptors as demonstrated by RT-PCR. GnRH
      antagonist AEZS-115 inhibited growth of all cell lines in a dose- and time
      dependent manner. Half maximal inhibitory concentration (IC(50)) values at 48 h
      of incubation were between 7 and 17.5 MUM and for 72 h between 4.5 and 12.5 MUM.
      IC(50) values for ovarian and endometrial cancer cells were rather similar. These
      results were obtained by tetrazolium salt [(3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide; MTT] assay and confirmed by additional crystal
      violet staining. Cell cycle FACS analysis revealed that AEZS-115 dose-dependently
      increased the fraction of apoptotic cells. Co-treatment experiments carried out
      with AEZS-115 and peptidic GnRH-antagonist cetrorelix suggest that the antitumor
      effect of AEZS-115 is not mediated by blockade of the GnRH receptor. CONCLUSION:
      GnRH antagonist AEZS-115 exhibited substantial antitumor activity in ovarian as
      well as endometrial cancer cell lines. However, this antitumor effect was not
      mediated by the tumoral GnRH receptors. To identify the mechanism of action of
      this compound, further research is warranted. Its in vitro antitumor activity
      makes AEZS-115 a promising candidate for in vivo studies of ovarian and
      endometrial cancer.

PMID- 22593490
TI  - Radiotherapy for giant cell tumors of the bone: a safe and effective treatment
      modality.
AB  - BACKGROUND: Giant cell tumor of the bone (GCTB) is a benign or sometimes semi
      malignant neoplasm accounting for 5% of all primary bone tumors. This type of
      tumor has been historically considered as radioresistant, but nowadays
      radiotherapy (RT) is used in unresectable, recurrent or incompletely resected
      cases. Since the value of RT is not well defined, a national cohort study was
      conducted. PATIENTS AND METHODS: Six German institutions collected data from 35
      patients treated during the last 35 years and analyzed them. RESULTS: From 1975
      2010 16 male and 19 female patients with 39 lesions were irradiated for GCTB. The
      median age was 30 years and the median follow-up 65 months. Nineteen patients had
      undergone RT for recurrent or unresectable disease and 16 patients for non-in
      sano resection. The actuarial 5-year overall and disease-free survival rates were
      90% and 59%, respectively. CONCLUSION: RT is an easy, safe and effective method
      for the treatment of GCTB. It may provide an attractive alternative to mutilating
      surgery.

PMID- 22593491
TI  - Methodological and preanalytical evaluation of a RAGE immunoassay.
AB  - BACKGROUND: Soluble receptor of advanced glycation end products (sRAGE) is a
      promising biomarker for the prognosis and the monitoring of cancer and of acute
      diseases such as trauma and sepsis. MATERIALS AND METHODS: We investigated the
      methodological characteristics of an ELISA for sRAGE (R&D Diagnostics) including
      intra- and inter-assay imprecision, dilution linearity and differences in various
      serum and plasma materials. Furthermore, the influence of various preanalytical
      factors such as time and storage temperature before and after centrifugation
      prior to definite deep freezing, as well as multiple freeze-thaw cycles, were
      tested. By the use of sera from 30 healthy individuals, a reference range and the
      dependency on patient characteristics was established. RESULTS: Intra-assay
      imprecision (coefficients of variation (CV): 6.0-11.5%) and inter-assay
      imprecision (5.9-7.8%) were in an acceptable range of manual assays. Linearity
      testing yielded satisfying results with dilution recoveries of 99-131%. Results
      of serum, EDTA-plasma (recovery of 85.9-114.7%), and heparin-plasma samples (88
      102%) were quite comparable, while results from citrate-plasma were slightly
      lower (78-96%). There was no influence of the time to centrifugation after 6 and
      24 hours (recoveries 87-102%) at storage temperatures of 4 degrees C and 25
      degrees C. Similarly, results were the same when samples were kept at 4 degrees C
      and 25 degrees C after centrifugation for up to 7 days (recoveries 88-109%).
      Repeated freeze-thawing of samples did not affect the results obtained for the
      RAGE protein (recoveries 92-104%). The median value of healthy individuals was
      1.10 ng/ml, with 90% limits of 0.52 to 1.49 ng/ml. CONCLUSION: sRAGE ELISA is a
      very robust and safe assay which produces reliable quantitative results for sera
      and plasma measurements.

PMID- 22593492
TI  - Surgical and oncological outcomes in patients with a preoperative PSA value <4
      ng/ml undergoing robot-assisted radical prostatectomy.
AB  - BACKGROUND: The objective of this study was to assess the surgical and
      oncological outcomes in patients with a preoperative prostate specific antigen
      (PSA) value <4 ng/ml undergoing robot-assisted radical prostatectomy (RARP) for
      prostate cancer. PATIENTS AND METHODS: The records of 2000 men who underwent RARP
      from February 2006 to April 2010, were retrospectively reviewed. A total of 169
      (8.4%) patients with a preoperative PSA value <4 ng/ml were identified. A
      comparison was performed between the overall patient cohort and the
      aforementioned patients. The analyzed parameters included: minor and major
      postoperative complications, postoperative Gleason score, pathological stage,
      positive margin status as well as presence of biochemical progression and of
      disease-specific mortality during the follow-up period. RESULTS: The following
      results reflect the comparison of the overall cohort of patients vs. the cohort
      of patients who had a preoperative PSA value <4 ng/ml. A statistical difference
      of the analyzed parameters was observed in the median PSA value; 10.3 ng/ml (0.3
      220 ng/ml) vs. 2.8 ng/ml (0.3-3.9 ng/ml) (p<0.001), in bilateral NVB; 65.7% vs.
      85.2% (p<0.001), in Gleason score <7; 42.8% vs. 59.1% (p<0.05), in Gleason score
      7; 47.7% vs. 36.6% (p<0.05) and in Gleason score >7 in 9.5% vs. 3.5% (p<0.001).
      Organ-confined disease was noted in 73.5% vs. 86.3% (p<0.05), extraprostatic
      extension in 25.2% vs. 13.7% (p<0.05). The percentage of cancer found in the
      prostate specimen was 16.1% (1-99%) vs. 7.3% (1-96%) (p<0.05) and a positive
      surgical margin status was encountered in 8.9% vs. 4.7% (p<0.05) of patients.
      Pelvic lymph node dissection was performed in 1623 patients (81.2%) of the
      overall cohort out of whom 64 cases (3.2%) were positive for metastasis. In the
      patient cohort of PSA value <4 ng/ml, pelvic lymph node dissection was performed
      in 114 patients (67.4%), out of which one case (0.5%) was positive for metastasis
      (p<0.05). After a median follow-up of 24.2 months (range 3-56 months), 162
      patients (95.8%) were free of biochemical progression and no disease-specific
      mortality was evident. CONCLUSION: RARP in patients with a preoperative PSA value
      <4 ng/ml is a safe surgical procedure with limited complications and excellent
      oncological outcome.

PMID- 22593493
TI  - Robotic-assisted radical prostatectomy in men >=75 years of age. Surgical,
      oncological and functional outcomes.
AB  - BACKGROUND: The aim of this study is to evaluate the surgical, the oncological
      and the functional outcomes in men >=75 years of age undergoing robot-assisted
      radical prostatectomy (RARP). PATIENTS AND METHODS: The records of N=2000 men who
      underwent RARP from February 2006 to April 2010 were retrospectively reviewed. A
      total of 45 patients who were >=75 years of age were indentified. A comparison
      was performed between the overall patient cohort and the aforementioned patients.
      The analyzed parameters included: minor and major postoperative complications,
      postoperative Gleason score, pathological stage, positive-margin status,
      continence and potency in 12 months, disease-specific mortality and presence of
      biochemical progression at the follow-up period. RESULTS: The following results
      reflect the comparison of the overall cohort of patients vs. the cohort of
      patients who were >=75 years of age. A statistical difference of the analyzed
      parameters was observed only minor complications 11.4% vs. 15.5% (p<0.05),
      neurovascular bundle (NVB) preservation 65.7% vs. 51.1% (p<0.05) and potency
      after 12 months 66.2% vs. 39.6% (p<0.001). Major complications were noted in 1.3%
      vs. 2.2% of cases. A Gleason score <7 was noted in 42.8% vs. 37.3%, a Gleason
      score 7 in 47.7% vs. 51.1% and a Gleason score >7 in 9.5% vs. 11.6%. Organ
      confined disease was noted in 73.5% vs. 68.8%, extraprostatic extension in 25.2%
      vs. 31.2% and positive surgical margin status was encountered in 8.9% vs. 11.1%
      of cases. At 12 months, 92.8% vs. 86.9% of patients were continent and 66.2% vs.
      39.6% were potent. After a median follow-up of 17.2 months no disease-specific
      mortality was evident and 95.5% were free of biochemical progression in the
      cohort of patients who were >=75 years of age. CONCLUSION: Our findings suggest
      that RARP in patients >=75 years of age is a safe surgical procedure with limited
      complications, excellent oncologic and continence outcomes as well as acceptable
      potency outcomes. Nevertheless, RARP should be limited to a selected cohort of
      patients with a good overal health status and an individual life expectancy of
      more than 10 years in order for the oncological advantages of surgery to be
      achieved.

PMID- 22593494
TI  - Surgical and oncological outcomes in patients with preoperative PSA >20 ng/ml
      undergoing robot-assisted radical prostatectomy.
AB  - BACKGROUND: The objective of this study was to assess the surgical and the
      oncological outcomes in patients with a preoperative prostate specific antigen
      (PSA) value >20 ng/ml, undergoing robot-assisted radical prostatectomy (RARP) for
      prostate cancer. PATIENTS AND METHODS: The records of 2000 men who underwent RARP
      from February 2006 to April 2010 were retrospectively reviewed. A total of 147
      (7.3%) patients with a preoperative PSA value >20 ng/ml were identified. A
      comparison was performed between the overall patient cohort and the patients with
      PSA >20 ng/ml. The analyzed parameters included: minor and major postoperative
      complications, postoperative Gleason score, pathological stage, positive margins
      and lymph node status, as well as biochemical progression and disease-specific
      mortality during the follow-up period. RESULTS: The following results reflect the
      comparison of the overall cohort of patients vs. the cohort of patients who had a
      preoperative PSA >20 ng/ml. A statistical difference of the analyzed parameters
      was observed for median PSA value 10.3 ng/ml vs. 34.8 ng/ml (p<0.05), for
      bilateral neurovascular bundle preservation 65.7% vs. 19.7% (p<0.001), for a
      Gleason score <7, 42.8% vs. 12.9% (p<0.05) and for a Gleason score >7 in 9.5% vs.
      19.7% (p<0.05). Organ-confined disease was noted in 73.5% vs. 31.9% (p<0.05) and
      extraprostatic extension in 25.2% vs. 86.1% (p<0.05). The percentage of cancer
      found in the prostate specimen was 16.1% vs. 38.1% (p<0.05) and a positive
      surgical margin (PSM) status was encountered in 8.9% vs. 33.3% (p<0.05) of
      patients. Positive lymph nodes were encountered in 3.2% vs. 17.1% of patients
      (p<0.05). After a median follow-up of 19.6 months (range 3-56 months), 118
      patients (80.2%) were free of biochemical progression and no disease-specific
      mortality was evident. CONCLUSION: Although RARP in patients with preoperative
      PSA >20 ng/ml is a safe surgical procedure with limited complications, the risk
      of positive lymph nodes, as well as the PSM status are found to be significantly
      higher. Patients should be informed of these probable outcomes, as well as for a
      possible need for adjuvant treatment before undergoing the procedure.

PMID- 22593495
TI  - Robotic-assisted radical prostatectomy in men <=50 years of age. Surgical,
      oncological and functional outcomes.
AB  - BACKGROUND: The aim of this study was to evaluate the surgical, oncological and
      functional outcomes in men <=50 years of age treated with robot-assisted
      laparoscopic radical prostatectomy (RARP). PATIENTS AND METHODS: The records of
      2000 men who underwent RARP from February 2006 to April 2010 were retrospectively
      reviewed. A total of 68 patients who were <=50 years of age were indentified. A
      comparison was performed between the overall patient cohort and the
      aforementioned patients. The analyzed parameters included: minor and major
      postoperative complications, postoperative Gleason score, pathological stage,
      positive margin status, continence and potency 12 months after treatment and
      presence of biochemical progression and disease-specific mortality during the
      follow-up period. RESULTS: The following results reflect the comparison of the
      overall cohort of patients vs. the cohort of patients who were <=50 years of age.
      A statistical difference of the analyzed parameters was observed in prostate
      weight 56.1 g vs. 31.4 g (p<0.05), in bilateral neurovascular bundle (NVB)
      preservation 65.7% vs. 92.6% (p<0.05), and in oncological and functional
      outcomes. Organ-confined disease was noted in 73.5% vs. 78.5% (p<0.05),
      extraprostatic extension in 25.2% vs. 21.5% (p<0.05) and positive surgical
      margins were encountered in 8.9% vs. 5.8% (p<0.05). A Gleason score <7 was noted
      in 42.8% vs. 54.4% (p<0.05), a Gleason score 7 in 47.7% vs. 41.2% (p<0.05) and a
      Gleason score >7 in 9.5% vs. 4.4% (p<0.05). At 12 months, 92.8% vs. 95.5% were
      continent and 66.2% vs. 93.7% (p<0.001) were potent. After a median follow-up of
      17.8 months, 97.1% patients of the <=50 years patient cohort were free of
      biochemical progression and no disease-specific mortality was evident.
      CONCLUSION: Our findings suggest that RARP in patients <=50 years of age is a
      safe surgical procedure with limited complications and excellent oncologial and
      functional outcomes. Although the preservation of the NVB in such patients is
      preferable, this can be performed without compromising the radical nature of
      cancer surgery.

PMID- 22593496
TI  - Multiple myeloma: myeloablative therapy with autologous stem cell support versus
      chemotherapy: a meta-analysis.
AB  - BACKGROUND: Myeloablative high-dose chemotherapy (HDT) followed by single
      autologous stem cell transplantation is currently the standard treatment for
      patients younger than 65 years with newly diagnosed multiple myeloma (MM).
      Several randomized controlled trials (RCTs) comparing HDT with standard dose
      therapy (SDT) have shown some benefit in overall survival (OS) and progression
      free survival (PFS), whereas other RCTs did not confirm this finding. In this
      study we attempted to analyze the current data in terms of the endpoints OS and
      PFS. MATERIALS AND METHODS: We searched PubMed, Embase, abstracts of former ASH
      meetings and ClinicalTrials.gov, as well as bibliographies of included trials,
      and recent reviews from September 2009 until May 2010. Amongst the 3,484 results
      in this search, we identified 10 RCTs comparing HDT with SDT on an intention-to
      treat-basis. Treatment characteristics and outcomes of OS and PFS were reported.
      We investigated statistical heterogenity and publication bias and performed
      subgroup analyses. RESULTS: Nine RCTs including 2,600 patients were fully
      analyzed. Patients undergoing HDT with stem cell transplantation had a
      significant PFS benefit (hazard ratio=0.73; 95% CI=0.56-0.95; p=0.02) but no OS
      benefit (HR 0.90; 95% CI 0.74-1.10; p=0.32) as compared to patients undergoing
      SDT. CONCLUSION: Although there is only a trend of OS benefit with HDT, it is
      currently still the first line treatment. Additional data from ongoing clinical
      trials and new studies using novel agents such as thalidomide, lenalidomide and
      bortezomib are warranted to finally evaluate the role of HDT in the treatment
      management of patients with newly diagnosed MM.

PMID- 22593497
TI  - Parenteral nutrition support for patients with pancreatic cancer--improvement of
      the nutritional status and the therapeutic outcome.
AB  - BACKGROUND: Malnutrition is a frequent and serious problem of patients with
      pancreatic cancer (i.e. due to exocrine pancreatic insufficiency, postoperative
      syndromes, anorexia, chemotherapy, and/or tumor progression). In many cases it
      has negative effects on the quality of life or on the tumor therapy. We
      investigated if malnutrition can be resolved or corrected by adequate home
      parenteral nutrition (PN) of pancreatic cancer (PaCa) patients, in cases where
      dietary advice and oral nutrition supplementation failed to correct the
      deficiencies. The energy supply via PN was analyzed in patients with PaCa, with
      focus on the single components in compounded PN. PATIENTS AND METHODS: We
      examined a group of six women and eleven men with assured PaCa disease at
      different tumor stages (mean age: 64 years). Indications for PN were a reduction
      of body weight of >5 % in three months and/or a long-term reduced nutritional
      status, reduced results of the bio-electrical impedance analysis (BIA),
      malassimilation and/or clinical symptoms like severe diarrhoea/vomitus,
      preventing adequate oral nutrition for weeks. The PN, administered via port
      catheter, was initiated while the patients were undergoing chemotherapy. The
      course of treatment was assessed based on body weight, BIA (Data-Input Nutriguard
      M), on laboratory parameters and on personal evaluation of the patients' quality
      of life. Retrospectively, the patients were subdivided into two groups (Gr): Gr1
      (n=10) had a survival period of more than 5, up to more than 37 months, after the
      start of PN and Gr2 (n=7) had a survival between 1-4 months after start of PN.
      The calculations of the energy supply were based on the patients' body weight
      (per kg). Fluid volume, relation of macronutrients and addition of fish oil to PN
      are described in detail. RESULTS: Gr1: Eight of ten patients already showed an
      increase of body weight with the initial PN, two patients after dose adaption.
      This positive impact was also observable on the cellular level by means of BIA
      results (phase angle, body cell mass (BCM), extracellular mass (ECM), cell
      content and ECM/BCM Index). Two patients, who were receiving PN for over two or
      three periods, showed reproducibility of the results; while when PN was
      interrupted all BIA parameters degraded and they ameliorated with the restart of
      PN. Gr2: In these patients PN was started in the late stage of the tumor disease
      in order to allow for a--from the retrospective point of view--last, but
      ineffective chemotherapy. The data indicated that the weight loss could be
      retarded, even if the effects on body weight and BIA parameters were found to be
      less pronounced compared to Gr1. The mean energy supply of both groups, however,
      was similar: 8,823 kcal (Gr1) per week compared to 9,572 kcal (Gr2) per week. The
      majority of patients claimed to be quicker and more powerful under PN and to some
      extent the appetite was enhanced. CONCLUSION: A timely onset of PN with
      sufficient calories leads to an improved nutritional status of patients with PaCa
      disease. PN enhances the quality of life, the administration of tumor therapy
      without interruption and therefore may lead to a better success of the entire
      therapy. For late-stage tumor patients (Gr2) the quality of life can, at least,
      be improved. The success of PN is significantly dependent upon the patients'
      compliance, which could be achieved through intensive consulting and support of
      all patients and their relatives.

PMID- 22593498
TI  - Nutritional parameters for patients with head and neck cancer.
AB  - AIM: Determination of the optimal nutritional parameter to provide useful
      information for the individual patient and assessing the impact of nutritional
      status have on the prognosis of head and neck cancer. PATIENTS AND METHODS:
      Firstly a retrospective study analysed the outcome of 110 patients in relation to
      initial weight loss and weight loss at the end of radiotherapy. A second study
      investigated the changing bioimpedance (BIA) data of 27 survivors and 39 patients
      who died between their first and last measurement during nutritional therapy (at
      least four weeks). RESULTS: A critical initial weight loss is 10 kg or more at
      the point of diagnosis. At the end of radiotherapy the body mass reduction should
      be less than 15 kg. Raw data of BIA reflect the changing nutritional status at
      the end of life. We observed a stabilized phase angle in survivors (4.7 degrees 
      to 5.2 degrees ) whereas patients who died exhibited a significant lower phase
      angle (4.6 degrees  to 3.7 degrees , p<0.05). CONCLUSION: The prognosis of head
      and neck cancer patients is highly related to their nutritional status. Specific
      nutritional anamnesis (initial weight loss, total weight loss, body mass index)
      and additional biophysical measurements such as BIA are recommended to monitor
      the individual status during the follow-up.

PMID- 22593499
TI  - Expression of podoplanin in nevoid basal cell carcinoma syndrome-associated
      keratocystic odontogenic tumours.
AB  - BACKGROUND: Keratocystic odontogenic tumour (KCOT) is a benign oral neoplasm of
      odontogenic origin. The majority of KCOT develop sporadically. The main
      differential diagnosis of KCOT is from other odontogenic cysts and ameloblastoma.
      In the rare nevoid basal cell carcinoma syndrome (NBCCS, synonym: Gorlin(-Goltz)
      Syndrome), however, KCOTs are frequently detected and may be the initial sign of
      this clinical syndrome. Podoplanin is a mucin-type transmembrane protein found in
      podocytes of human kidneys homologous to T1alpha-2. The expression of podoplanin
      in some other non-endothelial tissues raised our interest in studying this
      antibody in tissues of odontogenic origin. Recently, we reported podoplanin
      expression in sporadic cases of KCOT. We intended to investigate the podoplanin
      expression in KCOTs associated with NBCCS. MATERIALS AND METHODS: Archival
      paraffin embedded tissues from six KCOTs from patients with known NBCCCS were
      analyzed immunohistochemically with antibodies to podoplanin (D2-40) and p63.
      RESULTS: We observed a continuous linear immunoreactivity of basal epithelial
      cells for podoplanin in all cases. The staining intensity was strong and did not
      differ from that for KCOT in previously reported sporadic cases. Strong nuclear
      P63 expression was detected in basal cell layers and diminished in suprabasal
      layers. CONCLUSION: KCOTs exhibited enhanced podoplanin expression in a clinical
      setting of NBCCS. Although the biological functions of podoplanin have not yet
      been fully recognized, the overexpression of this protein is capable of promoting
      the formation of elongated cell extensions, and increasing adhesion and migration
      of inflammatory cells. Podoplanin expression in KCOT is possibly associated with
      slow invasion of the adjacent structures and the well-known frequent local tumour
      recurrences of this odontogenic tumour.

PMID- 22593500
TI  - Infiltration of colorectal carcinoma by S100+ dendritic cells and CD57+
      lymphocytes as independent prognostic factors after radical surgical treatment.
AB  - BACKGROUND: S100(+) dendritic cells and CD57(+) lymphocytes are factors
      reflecting the immune system's ability to suppress the progress of tumor growth.
      CD57(+) cells include natural killer cells and late stages of T-effector
      lymphocytes. We evaluated the relationship between the known clinical and
      histological factors and tumor markers as well as the presence of S100(+) and
      CD57(+) cells in the tissue of colorectal carcinoma with the aim of detecting
      patients at high risk of short overall survival (OS) or short disease-free
      interval (DFI) after radical surgical treatment and we further analyzed whether
      S100(+) and CD57(+) positivity could bring on new information regarding the
      treatment regimen. MATERIALS AND METHODS: Data of 150 patients (97 males and 53
      females) that underwent an elective radical surgical procedure for colorectal
      cancer were studied. The influence on DFI and on OS of the following parameters
      was evaluated: grading, staging and positivity for S100 and CD57 by
      immunohistochemical staining. We also analyzed the relation of preoperative serum
      levels of the tumor markers Carcinoembryonic Antigen (CEA), Cancer Antigen 19-9
      (CA19-9), Cancer Antigen 72-4 (CA72-4), Thymidine kinase (TK), Tissue-Specific
      Polypeptide Antigen (TPS) and Tissue Polypeptide Antigen (TPA) in relation to
      S100 and CD57 positivity/negativity for the same patients. RESULTS: OS at 1, 3
      and 5 years was 92.2%, 76.5% and 70.2%; the DFI at 1, 3 and 5 years was 85.3%,
      64.3% and 49.4%. CD57 positivity in the tumor mass was proven as a positive
      prognostic factor for OS. Risk of short OS was 2.5-fold higher in patients with
      low tumor infiltration by CD57(+) lymphocytes. The combination of N2 stage for
      lymph nodes and the absence of CD57(+) cells was proven to be the strongest
      negative prognostic factor for OS. No significant influence of CD57 positivity on
      DFI appeared. There was no significant influence of S100 positivity on OS or DFI;
      nor was there any statistical dependence of CD57 and S100 positivity or
      negativity on preoperative serum levels of CEA, CA19-9, CA72-4, TK, TPS or TPA.
      Both studied factors were shown to be statistically independent factors.
      CONCLUSION: The present study showed infiltration of colorectal cancer tissue by
      CD57(+) cells as being an important independent positive prognostic factor for
      OS.

PMID- 22593501
TI  - A retrospective in vitro study of the impact of anti-diabetics and
      cardioselective pharmaceuticals on breast cancer.
AB  - BACKGROUND: In a retrospective controlled study, a tumor-protective effect,
      regarding breast cancer, was determined for the medicines metformin and glitazone
      (anti-diabetics), bisoprolol, and propranolol (cardioselective beta1 adrenoceptor
      antagonists). Our main goal was to provide evidence, showing the tumor-protective
      effects of beta-blockers and of antidiabetics via investigations in vitro.
      MATERIALS AND METHODS: Four different medicines were tested in cell cultures:
      Propranolol: 2.4 mg/ml and 0.3 mg/ml; bisoprolol: 0.1 mg/ml and 0.05 mg/ml;
      metformin: 7.5 mg/ml, 2.5 mg/ml, and 0.15 mg/ml; and glitazone: 2.5 mg/ml, 0.15
      mg/ml, and 0.05 mg/ml. The human breast cancer cell lines MCF7 and BT20 (estrogen
      receptor-positive and -negative; ATCC; cell density: 5*10(5) cells/ml) were used.
      Both cell lines were cultured under sterile conditions in incubators at 37
      degrees C, with a humidified atmosphere of 5% CO(2). The influences of the drugs
      were determined through cytotoxicity and proliferation assays and performance of
      a hydrogen peroxide assay. Morphological observations (light microscopy) and
      metabolic investigations (pH value, glucose) were also performed. RESULTS: The
      application of the beta-blocker propranolol resulted in highly cytotoxic effects
      (>90%) in both cell lines. In contrast, bisoprolol did not have any effects,
      neither in cytotoxicity tests nor in cell proliferation assays. The anti-diabetic
      metformin had a higher cytotoxic influence on the BT20 than did on the MCF7 cell
      line. The cell proliferation of BT20 was significantly inhibited after the
      addition of 2.5 mg/ml metformin and of 2.5 mg/ml glitazone. The application of
      glitazone also resulted in an increase of hydrogen peroxide and a decrease of the
      pH value. CONCLUSION: The strongest cytotoxic effect was observed with
      propranolol suggesting that, in clinical practice, this pharmaceutical can be
      used in patients with breast cancer who have hypertension. A specific clinical
      recommendation for anti-diabetics is not yet possible.

PMID- 22593502
TI  - Vascular wall cells contribute to tumourigenesis in cutaneous neurofibromas of
      patients with neurofibromatosis type 1. A comparative histological,
      ultrastructural and immunohistochemical study.
AB  - Neurofibromas are benign nerve sheath tumours. They occur sporadically, singly or
      few in number, and in neurofibromatosis type 1 (NF1), an autosomal inherited
      disease. These tumours are composed of different cell types, e.g. nerve cells
      (axons and axon sheaths), Schwann cells, mast cells, and fibroblasts. The local
      control of tumour growth in NF1 is poorly understood. Identification of cell
      markers could provide new information on the processes that are involved in
      tumour growth. MATERIALS AND METHODS: NF1 patients were diagnosed according to
      the revised NF1 diagnostic criteria proposed by the US National Institute of
      Health. Fifteen cutaneous neurofibromas from eight patients (origin: trunk and
      face) were excised, immediately immersion-fixed in Bouin's fixative and embedded
      in paraffin. Six micrometre thin sections were incubated with a variety of
      neuronal markers, connective tissue and glial cell markers, neurotrophic factors
      and their receptors. In addition, material was fixed, embedded and further
      processed for light and electron microscopic studies. RESULTS: The tumours were
      composed of different cell types, e.g. nerve cells (axons and axon sheaths),
      Schwann cells, mast cells, compartmentalising cells and fibroblasts. Neuronal
      markers were identified in axons (neuron-specific protein gene product 9.5,
      PGP9.5), in several cell types (neurofilament protein-200 kDa, NF-200) and glial
      cells (protein S-100, S-100). In glial cells the immunoreactivity for fibroblast
      surface protein (FSP) was scanty, low for cyclic 2,3-nucleotide 3'
      phosphodiesterase (CNPase), strong for glucose transporter 1 (Glut-1) but lacking
      for glial fibrillary acidic protein (GFAP). Schwann cells and so-called
      compartmentalising cells exhibited immunoreactivity for neurotrophin receptor
      protein TrkA (TrkA) and glial cell-derived neurotrophic factor (GDNF). GDNF
      receptor alpha-1 (GFR-alpha1) exhibited distinct immunoreactivity in single
      axons, in Schwann cells, and with lower intensity in some perineurial sheet
      cells. No immunoreactivity was observed for the low-affinity neurotrophin
      receptor protein p75(NTR), high-affinity receptor protein TrkB (TrkB), high
      affinity receptor protein TrkC (TrkC), the neurotrophin 3 (NT-3), and the brain
      derived neurotrophic factor (BDNF). CONCLUSION: Human cutaneous neurofibromas
      displayed a pattern of neurotrophic factors and their receptor immunoreactivity,
      which is characteristic of differentiated non-malignant tumours, and exhibited
      some differences from that established in developing and differentiated control
      Schwann cells (probably involved in the pathogenesis of the neurofibromas), as
      well as tumour cells in the process of differentiation. Neurofibromas are highly
      vascularized tumours and possess activated endothelial cells and pericytes. We
      presume that most of the hyperplastic structural components of a neurofibroma are
      generated from activated pericytes and smooth muscle cells of the small tumour
      vessels which possess qualities of adult stem cells.

PMID- 22593503
TI  - Expression of the tumor markers sialyl Lewis A, sialyl Lewis X, Lewis Y, Thomsen
      Friedenreich antigen, galectin-1 and galectin-3 in human osteoblasts in vitro.
AB  - AIM: Lewis antigens and the Thomsen-Friedenreich (TF) antigen are complex glycan
      structures that modulate processes such as cell adhesion and proliferation and
      tumor metastasis. The aim of our study was to analyze the expression of sialyl
      Lewis A (sLeA), sialyl Lewis X (sLeX), Lewis Y (LeY), TF, galectin-1 (Gal-1) and
      galectin-3 (Gal-3) in human osteoblasts in vitro. MATERIALS AND METHODS: The
      expression of the tumor markers sLeA, sLeX, LeY, TF, Gal-1 and Gal-3 was studied
      by means of immunohistochemistry on cells grown on chamber slides (2D) and on
      paraffin sections three-dimensional scaffold-free cultures (3D). The results of
      the stainings were evaluated semiquantitatively with the immunoreactive scoring
      system (IRS). RESULTS: Analysis of sLeA expression in both types of culture, 2D
      and 3D showed no detectable staining. After 5 days, in the 2D culture, expression
      of sLeX was weak, but the 3D culture (after 56 weeks) displayed a strong
      expression. LeY was expressed very slightly in the 2D culture, however LeY was
      not detectable in the 3D culture. The TF epitope was identified in the 2D cell
      culture model. In the 3D model, however, TF was completely lacking. Gal-1 was
      expressed very strongly in 2D culture, but in the 3D culture was not detectable.
      In contrast, Gal-3 was expressed in 3D culture but not in 2D. CONCLUSION: Within
      this study, we present a systematic analysis of the expression of sLeA, sLeX,
      LeY, TF, Gal-1 and Gal-3 in human osteoblasts grown in 2D and in 3D scaffold-free
      cultures. Summarizing the results of our study, we suggest that Lewis antigens
      and Gal-1 and -3 might play an important role in cell-cell and cell-matrix
      interactions of osteoblastic cells.

PMID- 22593504
TI  - Squamous cell carcinoma of the sole of the foot in neurofibromatosis type 1.
AB  - Neurofibromatosis (NF1) is an autosomal dominant tumour predisposition syndrome.
      A plethora of tumours are described in the literature associated with NF1. These
      tumours usually develop earlier in life. Some tumours show a close association
      with NF1, e.g. malignant peripheral nerve sheath tumour and optic nerve glioma,
      others are only rarely diagnosed in the context of this disease. This report
      focuses on the diagnosis and therapy of a squamous cell carcinoma (SCC) of the
      sole of the foot arising in a 67-year-old male patient with NF1. The lesion was
      initially misdiagnosed as an abscess. Wide excision of the highly differentiated
      SCC was followed by conditioning of the deep wound by a vacuum dressing. After
      achievement of bulky granulation tissue covering the defect at the level of the
      adjacent skin, a full-thickness skin graft was obtained from the abdominal skin
      and fixed on the defect. Healing of the defect was almost achieved by primary
      intention; two small lesions healed within weeks. The patient was repeatedly
      investigated. Five years after primary surgery, the patient had developed a corn
      on the medial side of the former defect. This lesion was completely excised and
      the defect was closed by primary intention after creating a small rotation flap.
      The lesion proved to be inflamed skin of the sole of the foot with no
      dedifferentiation of the epithelia. NF1 is a complex hereditary disease that
      displays an abundance of signs and symptoms. SCC may affect individuals with NF1.
      However, SCC account only for a small number of malignancies in NF1 compared to
      malignancies arising in connective tissue and brain. To the best of our
      knowledge, this is the first report on an SCC of the sole diagnosed in NF1.
      Vacuum dressing as an adjunct to surgery allowed reduced reconstructive measures.

PMID- 22593505
TI  - Odontogenic myxomas are not associated with GNAS1 mutations.
AB  - Myxomas are rare tumors of unknown aetiology arising in the jaws. Myxomas are
      also diagnosed in soft tissues. Recent reports on Gs alpha subunit gene (GNAS1)
      mutations occasionally being identified in soft tissue myxomas in non-syndromatic
      patients and the effects of myxoma on bone in variants of fibrous dysplasia led
      us to re-examine the putative role of GNAS1 mutations in odontogenic myxoma.
      MATERIAL AND METHODS: Seven biopsies from patients with confirmed diagnosis of
      odontogenic myxoma and two cases of fibrous dyplasia of the jaw were investigated
      for GNAS1 mutations by polymerase chain reaction. RESULTS: Although GNAS1 was
      mutated in cases of fibrous dysplasia, no GNAS1 mutations were detected in
      odontogenic myxomas. CONCLUSION: The development of odontogenic myxoma is
      independent of mutations of GNAS1.

PMID- 22593506
TI  - Radiographic findings of odontogenic myxomas on conventional radiographs.
AB  - Odontogenic myxoma (OM) is a rare tumour arising in the jaws. The tumour is
      believed to be of odontogenic origin due to the close relation to teeth. The
      radiographic appearance of OM is not specific and the diagnosis is frequently
      unexpected following surgical removal of the lesion. The aim of this study was to
      analyse the radiographic appearance of OM on conventional radiographs. This type
      of radiographic diagnosis is typically used by dental practitioners. MATERIALS
      AND METHODS: We studied panoramic radiographs and plain skull radiographs of 14
      patients investigated over a period of 30 years (male: 3, female: 11; age at time
      of diagnosis: 8 to 45 years, <=16 years: 3). The maxilla was affected in five and
      the mandible in nine patients. In each case, all tumour findings were restricted
      to one jaw. RESULTS: Tumour size varied considerably. The largest tumours were
      seen in the distal parts of the mandible and ramus. Displacement of teeth was a
      frequent finding (8 cases), but root resorption was rare (2 cases). Honeycomb
      appearance on plain radiographs was associated with the size of the lesion and
      restricted to mandibular involvement. CONCLUSION: The radiographic appearance of
      OM of the jaws varies considerably. Large lesions may exhibit characteristic
      radiological signs of a slowly growing lesion. However, discrete displacement of
      teeth associated with a small osteolytic zone of the alveolar process between two
      teeth can be an OM. Careful interpretation of conventional radiographs is a must
      in identifying early lesions.

PMID- 22593507
TI  - Nature and dynamics of nucleosome release from neoplastic and non-neoplastic
      cells.
AB  - BACKGROUND: Circulating nucleosomes are elevated in the blood of patients with
      malignant and non-malignant diseases. Here, we investigated the nature and the
      dynamics of their release in functional cell studies. MATERIALS AND METHODS:
      Leukemia blasts were exposed to the intrinsic inducers of apoptotic cell death,
      cytosine arabinoside (AraC; 10 MUg/ml) and etoposide (50 MUg/ml), and cell death
      markers lactate dehydrogenase (LDH) and the nucleosomes were measured in the
      supernatants at 0, 24, 48, 72, and 96 hours after drug application. In addition,
      HepG2 cells were exposed to extrinsic apoptosis-inducing tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL; 0.5 and 1.0 ng/ml) and the nucleosomes
      were measured in the supernatants after 0, 24, 48, and 72 hours. Finally,
      neutrophils preactivated by phorbol myristate acetate (PMA) were co-incubated
      with platelet-rich plasma (PRP) in the presence of collagen (type I; 8 MUg/ml)
      for 15 or 30 minutes at 37 degrees C, and the nucleosome release into the
      supernatant was quantified. RESULTS: During treatment with AraC, cell viability
      constantly decreased. LDH and nucleosome levels increased at 24 h and peaked at
      48 h after exposure to AraC and etoposide. While LDH declined after 96 h, the
      nucleosomes' levels were still elevated. Similarly, nucleosomes increased dose
      dependently 24 h after exposure to TRAIL and reached a peak at 48 h. After 72 h,
      the nucleosomes' levels decreased again. While there was only a minor release of
      nucleosomes from PMA-stimulated neutrophils, co-incubation with PRP resulted in a
      strongly increased nucleosome release after 30 minutes. CONCLUSION: Nucleosomes
      are released from cells stimulated intrinsically or extrinsically to undergo
      apoptotic cell death in a time- and dose-dependent manner. Further mechanisms of
      release may be their active secretion from stimulated neutrophils when co
      incubated with PRP, as may be observed during bacterial inflammation and
      thrombosis.

PMID- 22593508
TI  - Determination of MUC1 in sera of ovarian cancer patients and in sera of patients
      with benign changes of the ovaries with CA15-3, CA27.29, and PankoMab.
AB  - AIM: Mucin 1 (MUC1) is a high molecular weight transmembrane glycoprotein with
      unique properties which is used as a tumour marker in sera of ovarian cancer
      patients. The common test kit for the cancer antigen 15-3 (CA15-3) is not
      sufficient for the discrimination between sera from healthy individuals and sera
      from patients with benign changes of the ovaries. In this study, the newly
      developed anti-MUC1 antibody PankoMab was tested in normal and patient sera with
      an ELISA, and the obtained data were compared against data from experiments using
      the commercial kits for CA15-3 and CA27.29. MATERIALS AND METHODS: Sera of 123
      patients diagnosed with benign or malignant changes of the ovaries were obtained
      before surgery. CA15-3 was analysed with an automated ELISA system (Immulite
      2000). CA27.29 was measured with the ST AIA-PACK CA27.29 for the AIA-600II
      Analyzer (Tosoh Bioscience, Belgium). The release of MUC1 fragments carrying the
      TA-MUC1 epitope was analysed with an ELISA using the PankoMab antibody. RESULTS:
      Using the already established markers CA15-3 and CA27.29, significant differences
      between benign and malignant changes of the ovaries were found. The same result
      was obtained with the newly developed TA-MUC1 test. In contrast to CA15-3 and
      CA27.29, however, the median of TA-MUC1 was lower in sera from patients with
      ovarian cancer compared to sera from patients with benign diseases of the ovary.
      However, sera of patients with benign ovarian diseases had significantly higher
      TA-MUC1 values compared to sera of healthy individuals. The risk score of TA-MUC1
      achieved an area under the curve (AUC) of 78.4% in receiver operating
      characteristic (ROC) curves and a sensitivity of 37% for the prediction of
      ovarian disease, at 95% specificity. CONCLUSION: In this study we employed an
      additional marker for MUC1 which recognizes a more tumour-specific MUC1 epitope
      (TA-MUC1). We obtained results showing significant differences between detection
      in benign and malignant ovarian diseases. Although the mean MUC1 values were
      elevated in sera of patients with ovarian cancer compared to values of patients
      with benign cysts, by using all three test systems, a different result was found
      by analysing the median TA-MUC1 values. PankoMab could be a useful, additional
      tool for obtaining conclusive information on the transformation process from
      benign to malignant state in ovarian tissues.

PMID- 22593509
TI  - Combination therapy with gemcitabine (GEM) and erlotinib (E) in exocrine
      pancreatic cancer under special reference to RASH and the tumour marker CA19-9.
AB  - We report on the results of a prospective treatment of 30 proven metastatic
      pancreatic cancer patients with the recently described combination of gemcitabine
      and erlotinib (GEM+E) (24* 1st line therapy, 8* 2nd line therapy). Eight of these
      patients received GEM+E for treatment of metastastic tumour recurrence after
      previous resective surgery, followed by adjuvant chemotherapy with gemcitabine.
      In 2 patients GEM+E was given as 1st line treatment and later, after complete
      response which was followed by a new recurrence, also as a second line therapy.
      The evaluation of RASH severity grades, the course of the serum tumour marker
      CA19-9 were determined every 14 days and the evaluation of the imaging methods CT
      or MRT, evaluated every 6-8 weeks, revealed the following results: there was a
      tendency for RASH grades to correlate with the tumour response, however, with
      observed exceptions. The decision for interruption or maintenance of GEM+E,
      therefore, should not be based on the RASH phenomenon, but on a detailed follow
      up with imaging methods and the relevant tumour markers as in the follow-up
      before erlotinib introduction into pancreatic cancer therapy. As known from
      previous studies tumour markers represent more sensitive parameters compared to
      the imaging methods. GEM+E was active in the whole group of patients, mainly
      given as 1st line therapy (34% PD, 29% SD, 47% MR, PR, CR), but also in the 2
      subgroups: in the patients with GEM+E as 2nd line therapy, as well as in patients
      after previous adjuvant gemcitabine therapy after tumour resection. In the 2
      patients with transient-CR after 1st line therapy with GEM+E the 2nd line therapy
      also resulted in a CR with long lasting remission. These data should motivate
      clinicians to focus their interest not only to 1st line therapy regimens with
      erlotinib, but also to 2nd and 3rd line strategies within the previously
      published concept of an efficacy-orientated sequential polychemotherapy or
      multimodal-therapy for pancreatic cancer.

PMID- 22593510
TI  - Relevance of histone marks H3K9me3 and H4K20me3 in cancer.
AB  - BACKGROUND: Circulating nucleosomes are valuable biomarkers for therapy
      monitoring and estimation of prognosis in cancer disease. While epigenetic and
      genetic modifications of DNA have been reported in blood of cancer patients,
      little is known about modifications of histones on circulating nucleosomes.
      PATIENTS AND METHODS: Sera of 45 cancer patients (21 colorectal, 4 pancreatic, 15
      breast, 5 lung cancer), 12 patients with benign gastrointestinal and inflammatory
      diseases, and 28 healthy individuals were investigated. Histone modifications
      were detected by chromatin-immunoprecipitation (ChIP) using antibodies for triple
      histone methylations at sites H3K9me3 and H4K20me3 and subsequent real-time
      polymerase chain reaction using primers for the centromeric satellites SAT2.
      Additionally, the amount of circulating nucleosomes, as well as of carcino
      embryonic antigen (CEA) and cancer antigen (CA) 19-9 were measured. RESULTS:
      Levels of SAT2 on H3K9me3 (median 0.507 ng/ml) and on H4K20me3 (0.292 ng/ml) were
      elevated in sera of patients with breast cancer when compared with healthy
      controls (0.049 and 0.035 ng/ml), but were lower in patients with colorectal
      cancer (0.039 and 0.027 ng/ml). Both histone marks were correlated with each
      other but did not correlate with CEA or CA 19-9 in cancer patients. When H3K9me3
      and H4K20me3 were normalized to nucleosome content in sera, ratios were
      significantly higher in all types of cancer as well as in colorectal and breast
      subtypes when compared with healthy controls. Best discrimination was achieved by
      normalized H4K20me3 reaching areas under the curves (AUC) of 79.1%, 90.4% and
      81.2% in receiver operating characteristic (ROC) curves of these three
      comparisons. CONCLUSION: SAT2 levels on H3K9me3 and H4K20me3 are up-regulated in
      breast cancer and down-regulated in colorectal cancer. Normalization to total
      nucleosome content enables better discrimination between cancer and control
      groups.

PMID- 22593511
TI  - Size of tooth crowns and position of teeth concerning the extension of facial
      plexiform neurofibroma in patients with neurofibromatosis type 1.
AB  - Neurofibromatosis type 1 (NF1) is an autosomal dominant inherited tumour
      syndrome. NF1 is also a disorder of bone in terms of altered bone metabolism and
      bone dysplasia. Facial plexiform neurofibroma (PNF) is frequently associated with
      osseous alterations and may cause severe disfigurement. These PNFs regularly
      affect the oral cavity and teeth. PNF pose many problems in reconstructive and
      oral surgery. This study was undertaken to describe oral findings related to PNFs
      and to investigate the size and position of teeth in these tumours. MATERIALS AND
      METHODS: Forty-eight patients with NF1 were investigated. Tumour type was
      histologically proven in all patients with PNF following aesthetic/functional
      orofacial surgery. Twenty-four patients were affected with a PNF and 24 had
      disseminated cutaneous neurofibroma (DCNF). In the PNF group, the side of the PNF
      was registered; PNF was unilateral in all cases. DCNF patients were 15 females
      and 9 males (mean age: 23.92+/-10.48 years, minimum: 6, maximum 45 years).
      Patients with PNF were 17 males and 7 females (mean age: 23.92+/-13.76 years,
      minimum 6, maximum 61 years). The right side was affected in 16 and the left in 8
      PNF patients. All patients were orally investigated and dental casts were
      obtained. Distances of the alveolar processes and of the teeth were measured in
      transverse and sagittal planes. In order to evaluate the possible impact of the
      tumour localisation inside the trigeminal nerve, the topography of the affected
      facial areas was assigned to the trigeminal nerve branches. Radiographs were
      taken to asses the formation of dental roots, to reveal retained teeth and to
      estimate dysplastic areas of the jaws. RESULTS: The size of tooth crowns did not
      differ from published standards on tooth parameters of Caucasian individuals. The
      dental arches were symmetrically arranged in all patients of the DCNF group.
      However, the position of teeth showed some relevant differences in the PNF group.
      We observed spacing between teeth, probably due to interdental invasion of
      plexiform neurofibroma or interference of tumour tissue with the mesial drift of
      teeth. Maxilla and mandible showed characteristic alterations in the PNF group
      that were confined to the side and extension of a PNF. CONCLUSION: Oral
      inspection should be carried out in all patients with NF1. Unilateral alterations
      of the position of teeth and asymmetries of the jaws should alert the
      investigator to search for an ipsilateral PNF of the second or third trigeminal
      branch. The size and dimensions of tooth crowns appear not to be affected by the
      disease.

PMID- 22593542
TI  - Thrombomodulin is an ezrin-interacting protein that controls epithelial
      morphology and promotes collective cell migration.
AB  - Adhesive interactions between cells are needed to maintain tissue architecture
      during development, tissue renewal and wound healing. Thrombomodulin (TM) is an
      integral membrane protein that participates in cell-cell adhesion through its
      extracellular lectin-like domain. However, the molecular basis of TM-mediated
      cell-cell adhesion is poorly understood. Here, we demonstrate that TM is linked
      to the actin cytoskeleton via ezrin. In vitro binding assays showed that the TM
      cytoplasmic domain bound directly to the N-terminal domain of ezrin. Mutational
      analysis of the TM cytoplasmic domain identified (522)RKK(524) as important ezrin
      binding residues. In epidermal epithelial A431 cells, TM colocalized with ezrin
      and actin filaments at cell-cell contacts. Knockdown of endogenous TM expression
      by RNA interference induced morphological changes and accelerated cell migration
      in A431 cells. Moreover, epidermal growth factor, upstream of ezrin activation,
      stimulated the interaction between ezrin and TM. In skin wound healing of mice,
      TM and ezrin were highly expressed in neoepidermis, implying that both proteins
      are key molecules in reepithelialization that requires collective cell migration
      of epithelial cells. Finally, exogenous expression of TM in TM-deficient melanoma
      A2058 cells promoted collective cell migration. In summary, TM, which associates
      with ezrin and actin filaments, maintains epithelial morphology and promotes
      collective cell migration.

PMID- 22593543
TI  - The death receptor 3/TL1A pathway is essential for efficient development of
      antiviral CD4+ and CD8+ T-cell immunity.
AB  - Death receptor 3 (DR3, TNFRSF25), the closest family relative to tumor necrosis
      factor receptor 1, promotes CD4(+) T-cell-driven inflammatory disease. We
      investigated the in vivo role of DR3 and its ligand TL1A in viral infection, by
      challenging DR3-deficient (DR3(KO)) mice and their DR3(WT) littermates with the
      beta-herpesvirus murine cytomegalovirus or the poxvirus vaccinia virus. The
      phenotype and function of splenic T-cells were analyzed using flow cytometry and
      molecular biological techniques. We report surface expression of DR3 by naive
      CD8(+) T cells, with TCR activation increasing its levels 4-fold and altering the
      ratio of DR3 splice variants. T-cell responses were reduced up to 90% in DR3(KO)
      mice during acute infection. Adoptive transfer experiments indicated this was
      dependent on T-cell-restricted expression of DR3. DR3-dependent CD8(+) T-cell
      expansion was NK and CD4 independent and due to proliferation, not decreased cell
      death. Notably, impaired immunity in DR3(KO) hosts on a C57BL/6 background was
      associated with 4- to 7-fold increases in viral loads during the acute phase of
      infection, and in mice with suboptimal NK responses was essential for survival
      (37.5%). This is the first description of DR3 regulating virus-specific T-cell
      function in vivo and uncovers a critical role for DR3 in mediating antiviral
      immunity.

PMID- 22593544
TI  - miR-146a regulates mechanotransduction and pressure-induced inflammation in small
      airway epithelium.
AB  - Mechanical ventilation generates biophysical forces, including high transmural
      pressures, which exacerbate lung inflammation. This study sought to determine
      whether microRNAs (miRNAs) respond to this mechanical force and play a role in
      regulating mechanically induced inflammation. Primary human small airway
      epithelial cells (HSAEpCs) were exposed to 12 h of oscillatory pressure and/or
      the proinflammatory cytokine TNF-alpha. Experiments were also conducted after
      manipulating miRNA expression and silencing the transcription factor NF-kappaB or
      toll-like receptor proteins IRAK1 and TRAF6. NF-kappaB activation, IL-6/IL-8/IL
      1beta cytokine secretion, miRNA expression, and IRAK1/TRAF6 protein levels were
      monitored. A total of 12 h of oscillatory pressure and TNF-alpha resulted in a 5-
      to 7-fold increase in IL-6/IL-8 cytokine secretion, and oscillatory pressure also
      resulted in a time-dependent increase in IL-6/IL-8/IL-1beta cytokine secretion.
      Pressure and TNF-alpha also resulted in distinct patterns of miRNA expression,
      with miR-146a being the most deregulated miRNA. Manipulating miR-146a expression
      altered pressure-induced cytokine secretion. Silencing of IRAK1 or TRAF6,
      confirmed targets of miR-146a, resulted in a 3-fold decrease in pressure-induced
      cytokine secretion. Cotransfection experiments demonstrate that miR-146a's
      regulation of pressure-induced cytokine secretion depends on its targeting of
      both IRAK1 and TRAF6. MiR-146a is a mechanosensitive miRNA that is rapidly up
      regulated by oscillatory pressure and plays an important role in regulating
      mechanically induced inflammation in lung epithelia.

PMID- 22593545
TI  - Nicotinamide nucleotide transhydrogenase (NNT) acts as a novel modulator of
      macrophage inflammatory responses.
AB  - Nicotinamide nucleotide transhydrogenase (NNT) is a mitochondrial redox-driven
      proton pump that couples the production of NADPH to the mitochondrial metabolic
      rate. In this study, we demonstrated for the first time that NNT has a
      significant effect in the modulation of the immune response and host defense
      against pathogens. We found that NNT mRNA is enriched in immune system-related
      tissues and regulated during macrophage activation. Overexpression of NNT in a
      macrophage cell-line resulted in decreased levels of reactive oxygen species
      (ROS) and nitric oxide upon induction of the macrophage inflammatory responses.
      These cells failed to fully activate MAPK signaling pathways, resulting in
      defective secretion of proinflammatory cytokines in response to LPS, and were
      inefficient in clearance of intracellular bacteria. We have shown that C57BL/6J
      mice, which have a deletion in the Nnt gene, exhibited greater resistance to
      acute pulmonary infection with Streptococcus pneumoniae. Macrophages from these
      mice generated more ROS and established a stronger inflammatory response to this
      pathogen. Our results demonstrate a novel role for NNT as a regulator of
      macrophage-mediated inflammatory responses.

PMID- 22593546
TI  - Timed high-fat diet resets circadian metabolism and prevents obesity.
AB  - Disruption of circadian rhythms leads to obesity and metabolic disorders. Timed
      restricted feeding (RF) provides a time cue and resets the circadian clock,
      leading to better health. In contrast, a high-fat (HF) diet leads to disrupted
      circadian expression of metabolic factors and obesity. We tested whether long
      term (18 wk) clock resetting by RF can attenuate the disruptive effects of diet
      induced obesity. Analyses included liver clock gene expression, locomotor
      activity, blood glucose, metabolic markers, lipids, and hormones around the
      circadian cycle for a more accurate assessment. Compared with mice fed the HF
      diet ad libitum, the timed HF diet restored the expression phase of the clock
      genes Clock and Cry1 and phase-advanced Per1, Per2, Cry2, Bmal1, Roralpha, and
      Rev-erbalpha. Although timed HF-diet-fed mice consumed the same amount of
      calories as ad libitum low-fat diet-fed mice, they showed 12% reduced body
      weight, 21% reduced cholesterol levels, and 1.4-fold increased insulin
      sensitivity. Compared with the HF diet ad libitum, the timed HF diet led to 18%
      lower body weight, 30% decreased cholesterol levels, 10% reduced TNF-alpha
      levels, and 3.7-fold improved insulin sensitivity. Timed HF-diet-fed mice
      exhibited a better satiated and less stressed phenotype of 25% lower ghrelin and
      53% lower corticosterone levels compared with mice fed the timed low-fat diet.
      Taken together, our findings suggest that timing can prevent obesity and rectify
      the harmful effects of a HF diet.

PMID- 22593547
TI  - Persistent signaling by thyrotropin-releasing hormone receptors correlates with G
      protein and receptor levels.
AB  - G-protein-coupled receptors with dissociable agonists for thyrotropin,
      parathyroid hormone, and sphingosine-1-phosphate were found to signal
      persistently hours after agonist withdrawal. Here we show that mouse thyrotropin
      releasing hormone (TRH) receptors, subtypes 2 and 1(TRH-R2 and TRH-R1), can
      signal persistently in HEK-EM293 cells under appropriate conditions, but TRH-R2
      exhibits higher persistent signaling activity. Both receptors couple primarily to
      Galpha(q/11). To gain insight into the mechanism of persistent signaling, we
      compared proximal steps of inositolmonophosphate (IP1) signaling by TRH-Rs.
      Persistent signaling was not caused by slower dissociation of TRH from TRH-R2
      (t(1/2)=77 +/- 8.1 min) compared with TRH-R1 (t(1/2)=82 +/- 12 min) and was
      independent of internalization, as inhibition of internalization did not affect
      persistent signaling (115% of control), but required continuously activated
      receptors, as an inverse agonist decreased persistent signaling by 60%.
      Galpha(q/11) knockdown decreased persistent signaling by TRH-R2 by 82%, and
      overexpression of Galpha(q/11) induced persistent signaling in cells expressing
      TRH-R1. Lastly, persistent signaling was induced in cells expressing high levels
      of TRH-R1. We suggest that persistent signaling by TRHRs is exhibited when
      sufficient levels of agonist/receptor/G-protein complexes are established and
      maintained and that TRH-R2 forms and maintains these complexes more efficiently
      than TRH-R1.

PMID- 22593548
TI  - CD137 on inflamed lymphatic endothelial cells enhances CCL21-guided migration of
      dendritic cells.
AB  - CD137/TNFR9/41BB was originally described as a surface molecule present on
      activated T and NK cells. However, its expression is broader among leukocytes,
      and it is also detected on hypoxic endothelial cells and inflamed blood vessels,
      as well as in atherosclerotic lesions. Here, we demonstrate that lymphatic
      endothelial cells (LECs) up-regulate CD137 expression from undetectable baseline
      levels on stimulation with TNF-alpha, LPS, and IL-1beta. CD137 cross-linking with
      an agonistic mAb results in NF-kappaB nuclear translocation, followed by up
      regulation of VCAM and a 3-fold increase in the production of the chemokine
      CCL21. Accordingly, there is a 50% increase in CCR7-dependent migration toward
      conditioned medium from activated LECs on CD137 cross-linking with the agonistic
      mAb or the natural ligand (CD137L). Such an enhancement of cell migration is also
      observed with monocyte-derived dendritic cells transmigrating across CD137
      activated LEC monolayers. Using explanted human dermal tissue, we found that
      inflamed skin contains abundant CD137(+) lymphatic vessels and that ex vivo
      incubation of explanted human dermis with TNF-alpha induces CD137 expression in
      lymphatic capillaries. More interestingly, treatment with CD137 agonistic
      antibody induces CCL21 expression and DC accumulation close to lymphatic vessels.
      Collectively, our results demonstrate that the inflammatory function of lymphatic
      vessels can be regulated by CD137.

PMID- 22593549
TI  - Mice lacking delta-opioid receptors resist the development of diet-induced
      obesity.
AB  - Pharmacological manipulation of opioid receptors alters feeding behavior.
      However, the individual contributions of each opioid receptor subtype on energy
      balance remain largely unknown. Herein, we investigated whether genetic
      disruption of the delta-opioid receptor (DOR) also controls energy homeostasis.
      Mice lacking DOR and wild-type mice were fed with standard diet and high-energy
      diet (HED). Mice were analyzed in vivo with the indirect calorimetry system, and
      tissues were analyzed by real-time PCR and Western blot analysis. DOR-knockout
      (KO) mice gained less weight (P<0.01) and had lower fat mass (P<0.01) when
      compared to WT mice fed an HED. Although DOR-KO mice were hyperphagic, they
      showed higher energy expenditure (P<0.05), which was the result of an increased
      activation of the thermogenic program in brown adipose tissue. The increased
      nonshivering thermogenesis involved the stimulation of uncoupling protein 1
      (UCP1; P<0.01), peroxisome proliferator-activated receptor gamma coactivator
      (PGC1alpha; P<0.05), and fibroblast growth factor 21 (FGF21; P<0.01). DOR
      deficiency also led to an attenuation of triglyceride content in the liver
      (P<0.05) in response to an HED. These findings reveal a novel role of DOR in the
      control of thermogenic markers and energy expenditure, and they provide a
      potential new therapeutic approach for the treatment of obesity.

PMID- 22593550
TI  - Centromere remodeling in Hoolock leuconedys (Hylobatidae) by a new transposable
      element unique to the gibbons.
AB  - Gibbons (Hylobatidae) shared a common ancestor with the other hominoids only 15
      18 million years ago. Nevertheless, gibbons show very distinctive features that
      include heavily rearranged chromosomes. Previous observations indicate that this
      phenomenon may be linked to the attenuated epigenetic repression of transposable
      elements (TEs) in gibbon species. Here we describe the massive expansion of a
      repeat in almost all the centromeres of the eastern hoolock gibbon (Hoolock
      leuconedys). We discovered that this repeat is a new composite TE originating
      from the combination of portions of three other elements (L1ME5, AluSz6, and
      SVA_A) and thus named it LAVA. We determined that this repeat is found in all the
      gibbons but does not occur in other hominoids. Detailed investigation of 46
      different LAVA elements revealed that the majority of them have target site
      duplications (TSDs) and a poly-A tail, suggesting that they have been
      retrotransposing in the gibbon genome. Although we did not find a direct
      correlation between the emergence of LAVA elements and human-gibbon synteny
      breakpoints, this new composite transposable element is another mark of the great
      plasticity of the gibbon genome. Moreover, the centromeric expansion of LAVA
      insertions in the hoolock closely resembles the massive centromeric expansion of
      the KERV-1 retroelement reported for wallaby (marsupial) interspecific hybrids.
      The similarity between the two phenomena is consistent with the hypothesis that
      evolution of the gibbons is characterized by defects in epigenetic repression of
      TEs, perhaps triggered by interspecific hybridization.

PMID- 22593551
TI  - Rooting gene trees without outgroups: EP rooting.
AB  - Gene sequences are routinely used to determine the topologies of unrooted
      phylogenetic trees, but many of the most important questions in evolution require
      knowing both the topologies and the roots of trees. However, general algorithms
      for calculating rooted trees from gene and genomic sequences in the absence of
      gene paralogs are few. Using the principles of evolutionary parsimony (EP) (Lake
      JA. 1987a. A rate-independent technique for analysis of nucleic acid sequences:
      evolutionary parsimony. Mol Biol Evol. 4:167-181) and its extensions (Cavender,
      J. 1989. Mechanized derivation of linear invariants. Mol Biol Evol. 6:301-316;
      Nguyen T, Speed TP. 1992. A derivation of all linear invariants for a nonbalanced
      transversion model. J Mol Evol. 35:60-76), we explicitly enumerate all linear
      invariants that solely contain rooting information and derive algorithms for
      rooting gene trees directly from gene and genomic sequences. These new EP linear
      rooting invariants allow one to determine rooted trees, even in the complete
      absence of outgroups and gene paralogs. EP rooting invariants are explicitly
      derived for three taxon trees, and rules for their extension to four or more taxa
      are provided. The method is demonstrated using 18S ribosomal DNA to illustrate
      how the new animal phylogeny (Aguinaldo AMA et al. 1997. Evidence for a clade of
      nematodes, arthropods, and other moulting animals. Nature 387:489-493; Lake JA.
      1990. Origin of the metazoa. Proc Natl Acad Sci USA 87:763-766) may be rooted
      directly from sequences, even when they are short and paralogs are unavailable.
      These results are consistent with the current root (Philippe H et al. 2011.
      Acoelomorph flatworms are deuterostomes related to Xenoturbella. Nature 470:255
      260).

PMID- 22593552
TI  - Measuring microsatellite conservation in mammalian evolution with a phylogenetic
      birth-death model.
AB  - Microsatellites make up ~3% of the human genome, and there is increasing evidence
      that some microsatellites can have important functions and can be conserved by
      selection. To investigate this conservation, we performed a genome-wide analysis
      of human microsatellites and measured their conservation using a binary character
      birth--death model on a mammalian phylogeny. Using a maximum likelihood method to
      estimate birth and death rates for different types of microsatellites, we show
      that the rates at which microsatellites are gained and lost in mammals depend on
      their sequence composition, length, and position in the genome. Additionally, we
      use a mixture model to account for unequal death rates among microsatellites
      across the human genome. We use this model to assign a probability-based
      conservation score to each microsatellite. We found that microsatellites near the
      transcription start sites of genes are often highly conserved, and that distance
      from a microsatellite to the nearest transcription start site is a good predictor
      of the microsatellite conservation score. An analysis of gene ontology terms for
      genes that contain microsatellites near their transcription start site reveals
      that regulatory genes involved in growth and development are highly enriched with
      conserved microsatellites.

PMID- 22593553
TI  - Re-evaluating the green versus red signal in eukaryotes with secondary plastid of
      red algal origin.
AB  - The transition from endosymbiont to organelle in eukaryotic cells involves the
      transfer of significant numbers of genes to the host genomes, a process known as
      endosymbiotic gene transfer (EGT). In the case of plastid organelles, EGTs have
      been shown to leave a footprint in the nuclear genome that can be indicative of
      ancient photosynthetic activity in present-day plastid-lacking organisms, or even
      hint at the existence of cryptic plastids. Here, we evaluated the impact of EGT
      on eukaryote genomes by reanalyzing the recently published EST dataset for
      Chromera velia, an interesting test case of a photosynthetic alga closely related
      to apicomplexan parasites. Previously, 513 genes were reported to originate from
      red and green algae in a 1:1 ratio. In contrast, by manually inspecting newly
      generated trees indicating putative algal ancestry, we recovered only 51 genes
      congruent with EGT, of which 23 and 9 were of red and green algal origin,
      respectively, whereas 19 were ambiguous regarding the algal provenance. Our
      approach also uncovered 109 genes that branched within a monocot angiosperm
      clade, most likely representing a contamination. We emphasize the lack of
      congruence and the subjectivity resulting from independent phylogenomic screens
      for EGT, which appear to call for extreme caution when drawing conclusions for
      major evolutionary events.

PMID- 22593554
TI  - Observation of dually decoded regions of the human genome using ribosome
      profiling data.
AB  - The recently developed ribosome profiling technique (Ribo-Seq) allows mapping of
      the locations of translating ribosomes on mRNAs with subcodon precision. When
      ribosome protected fragments (RPFs) are aligned to mRNA, a characteristic triplet
      periodicity pattern is revealed. We utilized the triplet periodicity of RPFs to
      develop a computational method for detecting transitions between reading frames
      that occur during programmed ribosomal frameshifting or in dual coding regions
      where the same nucleotide sequence codes for multiple proteins in different
      reading frames. Application of this method to ribosome profiling data obtained
      for human cells allowed us to detect several human genes where the same genomic
      segment is translated in more than one reading frame (from different transcripts
      as well as from the same mRNA) and revealed the translation of hitherto
      unpredicted coding open reading frames.

PMID- 22593555
TI  - Dynamics of enhancer chromatin signatures mark the transition from pluripotency
      to cell specification during embryogenesis.
AB  - The generation of distinctive cell types that form different tissues and organs
      requires precise, temporal and spatial control of gene expression. This depends
      on specific cis-regulatory elements distributed in the noncoding DNA surrounding
      their target genes. Studies performed on mammalian embryonic stem cells and
      Drosophila embryos suggest that active enhancers form part of a defined chromatin
      landscape marked by histone H3 lysine 4 mono-methylation (H3K4me1) and histone H3
      lysine 27 acetylation (H3K27ac). Nevertheless, little is known about the dynamics
      and the potential roles of these marks during vertebrate embryogenesis. Here, we
      provide genomic maps of H3K4me1/me3 and H3K27ac at four developmental time-points
      of zebrafish embryogenesis and analyze embryonic enhancer activity. We find that
      (1) changes in H3K27ac enrichment at enhancers accompany the shift from
      pluripotency to tissue-specific gene expression, (2) in early embryos, the peaks
      of H3K27ac enrichment are bound by pluripotent factors such as Nanog, and (3) the
      degree of evolutionary conservation is higher for enhancers that become marked by
      H3K27ac at the end of gastrulation, suggesting their implication in the
      establishment of the most conserved (phylotypic) transcriptome that is known to
      occur later at the pharyngula stage.

PMID- 22593556
TI  - Sulfamate proton solvent exchange in heparin oligosaccharides: evidence for a
      persistent hydrogen bond in the antithrombin-binding pentasaccharide Arixtra.
AB  - Sulfamate groups (NHSO(3)(-)) are important structural elements in the
      glycosaminoglycans (GAGs) heparin and heparan sulfate (HS). In this work, proton
      nuclear magnetic resonance (NMR) line-shape analysis is used to explore the
      solvent exchange properties of the sulfamate NH groups within heparin-related
      mono-, di-, tetra- and pentasaccharides as a function of pH and temperature. The
      results of these experiments identified a persistent hydrogen bond within the
      Arixtra (fondaparinux sodium) pentasaccharide between the internal glucosamine
      sulfamate NH and the adjacent 3-O-sulfo group. This discovery provides new
      insights into the solution structure of the Arixtra pentasaccharide and suggests
      that 3-O-sulfation of the heparin N-sulfoglucosamine (GlcNS) residues pre
      organize the secondary structure in a way that facilitates binding to
      antithrombin-III. NMR studies of the GlcNS NH groups can provide important
      information about heparin structure complementary to that available from NMR
      spectral analysis of the carbon-bound protons.

PMID- 22593557
TI  - Manipulation and imaging of Kryptolebias marmoratus embryos.
AB  - The self-fertilizing mangrove killifish, Kryptolebias marmoratus, is an upcoming
      model species for a range of biological disciplines. To further establish this
      model in the field of developmental biology, we examined several techniques for
      embryonic manipulation and for imaging that can be used in an array of
      experimental designs. These methodological approaches can be divided into two
      categories: handling of embryos with and without their chorionic membrane.
      Embryos still enclosed in their chorion can be manipulated using an agarose bed
      or a methyl cellulose system, holding them in place and allowing their rotation
      to more specific angles and positions. Using these methods, we demonstrate
      microinjection of embryos and monitoring of fluorescent yolk syncytial nuclei
      (YSN) using both stereo and compound microscopes. For higher magnification
      imaging using compound microscopes as well as time-lapse analyses, embryos were
      dechorionated and embedded in low-melting-point agarose. To demonstrate this
      embedding technique, we further examined fluorescent YSN and also analyzed the
      yolk surface of K. marmoratus embryos. The latter was observed to provide an
      excellent imaging platform for study of the behavior and morphology of cells
      during embryonic development, for various types of cells. Our data demonstrate
      that K. marmoratus is an excellent model species for research in developmental
      biology, as methodological approaches for the manipulation and imaging of embryos
      are efficient and readily available.

PMID- 22593558
TI  - Microevolutionary distribution of isogenicity in a self-fertilizing fish
      (Kryptolebias marmoratus) in the Florida Keys.
AB  - The mangrove rivulus Kryptolebias marmoratus and a closely related species are
      the world's only vertebrates that routinely self-fertilize. Such uniqueness
      presents a model for understanding why this reproductive mode, common in plants
      and invertebrates, is so rare in vertebrates. A survey of 32 highly polymorphic
      loci in >200 specimens of mangrove rivulus from multiple locales in the Florida
      Keys, USA, revealed extensive population-genetic structure on microspatial and
      micro-temporal scales. Observed heterozygosities were severely constrained, as
      expected for a hermaphroditic species with a mixed-mating system and low rates of
      outcrossing. Despite the pronounced population structure and the implied
      restrictions on effective gene flow, isogenicity (genetic identity across
      individuals) within and among local inbred populations was surprisingly low even
      after factoring out probable de novo mutations. Results indicate that neither
      frequent bottlenecks nor directional genetic adaptation to local environmental
      conditions were the primary driving forces impacting multilocus population
      genetic architecture in this self-fertilizing vertebrate species. On the other
      hand, a high diversity of isogenic lineages within relatively small and isolated
      local populations is consistent with the action of diversifying selection driven
      by the extreme spatio-temporal environmental variability that is characteristic
      of mangrove habitats.

PMID- 22593559
TI  - The integrated phenotype.
AB  - Proper functioning of complex phenotypes requires that multiple traits work
      together. Examination of relationships among traits within and between complex
      characters and how they interact to function as a whole organism is critical to
      advancing our understanding of evolutionary developmental plasticity. Phenotypic
      integration refers to the relationships among multiple characters of a complex
      phenotype, and their relationships with other functional units (modules) in an
      organism. In this review, I summarize a brief history of the concept of
      phenotypic integration in plant and animal biology. Following an introduction of
      concepts, including modularity, I use an empirical case-study approach to
      highlight recent advance in clarifying the developmental and genomic basis of
      integration. I end by highlighting some novel approaches to genomic and
      epigenetic perturbations that offer promise in further addressing the role of
      phenotypic integration in evolutionary diversification. In the age of the
      phenotype, studies that examine the genomic and developmental changes in
      relationships of traits across environments will shape the next chapter in our
      quest for understanding the evolution of complex characters.

PMID- 22593561
TI  - False aneurysm of ascending aorta due to pericardial mesothelioma.
AB  - Ascending aortic false aneurysm is a rare but serious complication of pericardial
      mesothelioma. We report a case of ascending aortic pseudoaneurysm due to spindle
      cell pericardial mesothelioma. In this case, the first symptoms of the disease
      appeared 18 months before surgery. The final diagnosis was determined only when
      severe late complications occurred. Palliative tumour excision, aortoplasty and
      aortic valve prosthesis were performed with subsequent adjuvant chemotherapy.
      Over 10 months after surgery, the patient is alive and a significant reduction of
      the tumour mass has been achieved. This case demonstrates that timely lifetime
      diagnosis of malignant pericardial tumour remains very difficult and effective
      adjuvant chemotherapy is needed to improve the results of surgery.

PMID- 22593562
TI  - Gastric ulceration following oesophageal stent migration complicating surgical
      management of oesophageal cancer.
AB  - Oesophageal, fully covered self-expanding metal stents (SEMS) allow palliation of
      dysphagia so as to support nutrition during neoadjuvant therapy. We present a 68
      year old man with an oesophageal adenocarcinoma (T3N1M0) who had a fully covered
      oesophageal SEMS placed prior to neoadjuvant chemoradiotherapy. Repeat endoscopy
      8 weeks later (for stent removal) showed that the stent had migrated and impacted
      upon the greater curvature of the stomach with a resultant ulcer. Surgery was
      delayed and, 10 weeks following the cessation of neoadjuvant chemoradiotherapy,
      this patient underwent a right thoracoabdominal oesophagogastrectomy. Operative
      findings included an erosion of the stent-induced gastric ulcer into the body of
      the pancreas and showed that the ulcerated tumour had become adherent to the
      thoracic aorta. This report demonstrates that the complications of stent
      migration can significantly impact upon surgical resection at multiple levels and
      provides a case for the routine removal of stents used in the neoadjuvant
      setting.

PMID- 22593563
TI  - Segmentectomy guided by three-dimensional computed tomography angiography and
      bronchography.
AB  - We describe the benefits of a three-dimensional multidetector computed tomography
      angiography and the bronchography-guided segmentectomy technique. Preoperative
      determination of the anatomical intersegmental plane is possible by visualizing
      the segmental branches of the pulmonary veins and segmental bronchi. This new
      technique may be useful in segmentectomy of the lung.

PMID- 22593564
TI  - The role of eis mutations in the development of kanamycin resistance in
      Mycobacterium tuberculosis isolates from the Moscow region.
AB  - OBJECTIVES: Kanamycin is an important second-line drug used to treat multidrug
      resistant (MDR) tuberculosis (TB). Molecular analysis of the rrs gene seems to be
      not enough to identify every case of kanamycin resistance. In the present study
      we evaluated the incidence of eis mutations in kanamycin-resistant Mycobacterium
      tuberculosis isolates. METHODS: We analysed 70 MDR M. tuberculosis clinical
      isolates. All isolates were screened for rrs and eis mutations using single
      strand conformation polymorphism and sequencing. Phenotypic drug susceptibility
      testing was performed using Bactec MGIT 960 and the absolute concentration method
      on Lowenstein-Jensen medium. RESULTS: eis mutations were found in 10 isolates.
      The most prevalent mutations were the A1401G substitution in the rrs gene and the
      C14T substitution in the eis promoter region. CONCLUSIONS: Our study shows that
      the eis promoter region is a useful molecular marker of kanamycin resistance in
      the Moscow region. Complex analysis of rrs and eis mutations will significantly
      reduce the time to diagnose kanamycin resistance in TB patients, compared with
      phenotypic drug resistance testing.

PMID- 22593565
TI  - Detection and quantification of new designer drugs in human blood: Part 2 -
      Designer cathinones.
AB  - In recent years, derivatives of cathinone, a naturally occurring beta-keto
      phenylethylamine, have entered the illicit drug market. These compounds have been
      marketed over the internet or in so-called head shops as "legal highs" and have
      gained popularity among drug users. Numerous fatalities due to the abuse of these
      drugs in recent years have increased the need for their detection in human blood
      samples. For detection and determination of 25 designer cathinones and their
      related ephedrines in blood samples, a liquid chromatography-tandem mass
      spectrometry (LC-MS-MS) method was developed using only 100 uL of blood. The
      blood was extracted using liquid-liquid extraction with 1 mL of 1-chlorobutane
      containing 10% of isopropanol. The final extract was analyzed using a Shimadzu
      8030 LC-MS-MS system operated in electrospray positive ionization multiple
      reaction monitoring mode. The method has been validated according to
      international guidelines and was found to be selective for all tested compounds.
      Calibration for all 25 studied analytes was satisfactory from 10-1,000 ng/mL.
      Accuracy data were within the acceptance interval of +/-15% [+/-20% at the lower
      limit of quantification (LLOQ)] of the nominal values for all drugs. Within-day
      (repeatability) and intermediate precision data were within the required limits
      of 15% relative standard deviation (RSD) (20% RSD at LLOQ).

PMID- 22593566
TI  - Cocaine analytes in human hair: evaluation of concentration ratios in different
      cocaine sources, drug-user populations and surface-contaminated specimens.
AB  - Hair specimens were analyzed for cocaine (COC), benzoylecgonine (BE),
      cocaethylene (CE) and norcocaine (NCOC) by liquid chromatography-tandem mass
      spectrometry. Drug-free hair was contaminated in vitro with COC from different
      sources with varied COC analyte concentrations. Results were compared to COC
      analyte concentrations in drug users' hair following self-reported COC use
      (Street) and in hair from participants in controlled COC administration studies
      (Clinical) on a closed clinical research unit. Mean +/- standard error analyte
      concentrations in Street drug users' hair were COC 27,889 +/- 7,846 (n = 38); BE
      8,132 +/- 2,523 (n = 38); CE 901 +/- 320 (n = 20); NCOC 345 +/- 72 pg/mg (n =
      32). Mean percentages to COC concentration were BE 29%, CE 3% and NCOC 1%.
      Concentrations in hair were lower for Clinical participants. COC contamination
      with higher CE, BE or NCOC content produced significantly higher concentrations
      (P = 0.0001) of all analytes. CE/COC and NCOC/COC ratios did not improve
      differentiation of COC use from COC contamination. COC concentrations in illicit
      and pharmaceutical COC affect concentrations in contaminated hair. Criteria for
      distinguishing COC use from contamination under realistic concentrations were not
      significantly improved by adding CE and NCOC criteria to COC cutoff concentration
      and BE/COC ratio criteria. Current criteria for COC hair testing in many forensic
      drug-testing laboratories may not effectively discriminate between COC use and
      environmental COC exposure.

PMID- 22593567
TI  - Detection and quantification of new designer drugs in human blood: Part 1 -
      Synthetic cannabinoids.
AB  - Synthetic cannabinoids sprayed on herbal mixtures have been abused as a new
      designer drug all over the world since 2004. In 2008, the first compounds, CP
      47,497 and JWH-018, were identified as active ingredients in these mixtures. Most
      of the compounds have been synthesized for research purposes and are potent CB1
      and/or CB2 receptor agonists. To investigate the presence of synthetic
      cannabinoids in blood samples, a liquid chromatography-tandem mass spectrometry
      (LC-MS-MS) method was developed using only 100 uL of blood. After the addition of
      0.2 mL of trizma buffer, the blood was extracted using liquid-liquid extraction
      with 1 mL of 1-chlorobutane containing 10% of isopropanol for 5 min on a shaker
      at 1,500 rpm. After centrifugation at 12,000 rpm for 1 min, the separated solvent
      layer was transferred to an autosampler vial and evaporated to dryness under N2.
      The residue was reconstituted in methanol and injected into a Shimadzu 8030 LC-MS
      MS system to separate and detect 25 synthetic cannabinoids. The method has been
      validated according to international guidelines and was found to be selective for
      all tested compounds. Calibration was satisfactory from 0.5-100 ng/mL, and from
      5.0-500 ng/mL. for HU-210, CP 47,497 and the CP 47,497 C-8 homolog, respectively.
      The extraction efficiencies ranged from 30-101% and the matrix effects from 67
      112%. Accuracy data were within the acceptance interval of +/-15% (+/-20% at the
      lower limit of quantification) of the nominal values for all drugs.

PMID- 22593568
TI  - PG0026 is the C-terminal signal peptidase of a novel secretion system of
      Porphyromonas gingivalis.
AB  - Protein substrates of a novel secretion system of Porphyromonas gingivalis
      contain a conserved C-terminal domain (CTD) of ~70-80 amino acid residues that is
      essential for their secretion and attachment to the cell surface. The CTD itself
      has not been detected in mature substrates, suggesting that it may be removed by
      a novel signal peptidase. More than 10 proteins have been shown to be essential
      for the proper functioning of the secretion system, and one of these, PG0026, is
      a predicted cysteine proteinase that also contains a CTD, suggesting that it may
      be a secreted component of the secretion system and a candidate for being the CTD
      signal peptidase. A PG0026 deletion mutant was constructed along with a
      PG0026C690A targeted mutant encoding an altered catalytic Cys residue. Analysis
      of clarified culture fluid fractions by SDS-PAGE and mass spectrometry revealed
      that the CTD was released intact into the surrounding medium in the wild type
      strain, but not in the PG0026 mutant strains. Western blot experiments revealed
      that the maturation of a model substrate was stalled at the CTD-removal step
      specifically in the PG0026 mutants, and whole cell ELISA experiments demonstrated
      partial secretion of substrates to the cell surface. The CTD was also shown to be
      accessible at the cell surface in the PG0026 mutants, suggesting that the CTD was
      secreted but could not be cleaved. The data indicate that PG0026 is responsible
      for the cleavage of the CTD signal after substrates are secreted across the OM.

PMID- 22593570
TI  - Overexpression of the Coq8 kinase in Saccharomyces cerevisiae coq null mutants
      allows for accumulation of diagnostic intermediates of the coenzyme Q6
      biosynthetic pathway.
AB  - Most of the Coq proteins involved in coenzyme Q (ubiquinone or Q) biosynthesis
      are interdependent within a multiprotein complex in the yeast Saccharomyces
      cerevisiae. Lack of only one Coq polypeptide, as in Deltacoq strains, results in
      the degradation of several Coq proteins. Consequently, Deltacoq strains
      accumulate the same early intermediate of the Q(6) biosynthetic pathway; this
      intermediate is therefore not informative about the deficient biosynthetic step
      in a particular Deltacoq strain. In this work, we report that the overexpression
      of the protein Coq8 in Deltacoq strains restores steady state levels of the
      unstable Coq proteins. Coq8 has been proposed to be a kinase, and we provide
      evidence that the kinase activity is essential for the stabilizing effect of Coq8
      in the Deltacoq strains. This stabilization results in the accumulation of
      several novel Q(6) biosynthetic intermediates. These Q intermediates identify
      chemical steps impaired in cells lacking Coq4 and Coq9 polypeptides, for which no
      function has been established to date. Several of the new intermediates contain a
      C4-amine and provide information on the deamination reaction that takes place
      when para-aminobenzoic acid is used as a ring precursor of Q(6). Finally, we used
      synthetic analogues of 4-hydroxybenzoic acid to bypass deficient biosynthetic
      steps, and we show here that 2,4-dihydroxybenzoic acid is able to restore Q(6)
      biosynthesis and respiratory growth in a Deltacoq7 strain overexpressing Coq8.
      The overexpression of Coq8 and the use of 4-hydroxybenzoic acid analogues
      represent innovative tools to elucidate the Q biosynthetic pathway.

PMID- 22593569
TI  - Structural and mechanistic studies of pesticin, a bacterial homolog of phage
      lysozymes.
AB  - Yersinia pestis produces and secretes a toxin named pesticin that kills related
      bacteria of the same niche. Uptake of the bacteriocin is required for activity in
      the periplasm leading to hydrolysis of peptidoglycan. To understand the uptake
      mechanism and to investigate the function of pesticin, we combined crystal
      structures of the wild type enzyme, active site mutants, and a chimera protein
      with in vivo and in vitro activity assays. Wild type pesticin comprises an
      elongated N-terminal translocation domain, the intermediate receptor binding
      domain, and a C-terminal activity domain with structural analogy to lysozyme
      homologs. The full-length protein is toxic to bacteria when taken up to the
      target site via the outer or the inner membrane. Uptake studies of deletion
      mutants in the translocation domain demonstrate their critical size for import.
      To further test the plasticity of pesticin during uptake into bacterial cells,
      the activity domain was replaced by T4 lysozyme. Surprisingly, this replacement
      resulted in an active chimera protein that is not inhibited by the immunity
      protein Pim. Activity of pesticin and the chimera protein was blocked through
      introduction of disulfide bonds, which suggests unfolding as the prerequisite to
      gain access to the periplasm. Pesticin, a muramidase, was characterized by active
      site mutations demonstrating a similar but not identical residue pattern in
      comparison with T4 lysozyme.

PMID- 22593571
TI  - Yeast aquaglyceroporins use the transmembrane core to restrict glycerol
      transport.
AB  - Aquaglyceroporins are transmembrane proteins belonging to the family of
      aquaporins, which facilitate the passage of specific uncharged solutes across
      membranes of cells. The yeast aquaglyceroporin Fps1 is important for
      osmoadaptation by regulating intracellular glycerol levels during changes in
      external osmolarity. Upon high osmolarity conditions, yeast accumulates glycerol
      by increased production of the osmolyte and by restricting glycerol efflux
      through Fps1. The extended cytosolic termini of Fps1 contain short domains that
      are important for regulating glycerol flux through the channel. Here we show that
      the transmembrane core of the protein plays an equally important role. The
      evidence is based on results from an intragenic suppressor mutation screen and
      domain swapping between the regulated variant of Fps1 from Saccharomyces
      cerevisiae and the hyperactive Fps1 ortholog from Ashbya gossypii. This suggests
      a novel mechanism for regulation of glycerol flux in yeast, where the termini
      alone are not sufficient to restrict Fps1 transport. We propose that glycerol
      flux through the channel is regulated by interplay between the transmembrane
      helices and the termini. This mechanism enables yeast cells to fine-tune
      intracellular glycerol levels at a wide range of extracellular osmolarities.

PMID- 22593572
TI  - Poxviral protein A46 antagonizes Toll-like receptor 4 signaling by targeting BB
      loop motifs in Toll-IL-1 receptor adaptor proteins to disrupt receptor:adaptor
      interactions.
AB  - Toll-like receptors (TLRs) have an anti-viral role in that they detect viruses,
      leading to cytokine and IFN induction, and as such are targeted by viruses for
      immune evasion. TLR4, although best known for its role in recognizing bacterial
      LPS, is also strongly implicated in the immune response to viruses. We previously
      showed that the poxviral protein A46 inhibits TLR4 signaling and interacts with
      Toll-IL-1 receptor (TIR) domain-containing proteins of the receptor complex.
      However the exact molecular mechanism whereby A46 disrupts TLR4 signaling remains
      to be established, and may yield insight into how the TLR4 complex functions,
      since viruses often optimally target key residues and motifs on host proteins for
      maximal efficiency. Here we show that A46 targets the BB loop motif of TIR
      proteins and thereby disrupts receptor:adaptor (TLR4:Mal and TLR4:TRAM), but not
      receptor:receptor (TLR4:TLR4) nor adaptor:adaptor (Mal:MyD88, TRAM:TRIF, and
      Mal:Mal) TIR interactions. The requirement for an intact BB loop for TIR adaptor
      interactions correlated with the protein:protein interfaces antagonized by A46.
      We previously discovered a peptide fragment derived from A46 termed VIPER (Viral
      Inhibitory Peptide of TLR4), which specifically inhibits TLR4 responses. Here we
      demonstrate that the region of A46 from which VIPER is derived represents the
      TLR4-specific inhibitory motif of the intact protein, and is essential for
      A46:TRAM interactions. This study provides the molecular basis for pathogen
      subversion of TLR4 signaling and clarifies the importance of TIR motif BB loops,
      which have been selected for viral antagonism, in the formation of the TLR4
      complex.

PMID- 22593573
TI  - Time-resolved Fourier transform infrared spectroscopy of the nucleotide-binding
      domain from the ATP-binding Cassette transporter MsbA: ATP hydrolysis is the rate
      limiting step in the catalytic cycle.
AB  - MsbA is an essential Escherichia coli ATP-binding cassette (ABC) transporter
      involved in the flipping of lipid A across the cytoplasmic membrane. It is a
      close homologue of human P-glycoprotein involved in multidrug resistance, and it
      similarly accepts a variety of small hydrophobic xenobiotics as transport
      substrates. X-ray structures of three full-length ABC multidrug exporters
      (including MsbA) have been published recently and reveal large conformational
      changes during the transport cycle. However, how ATP hydrolysis couples to these
      conformational changes and finally the transport is still an open question. We
      employed time-resolved FTIR spectroscopy, a powerful method to elucidate
      molecular reaction mechanisms of soluble and membrane proteins, to address this
      question with high spatiotemporal resolution. Here, we monitored the hydrolysis
      reaction in the nucleotide-binding domain of MsbA at the atomic level. The
      isolated MsbA nucleotide-binding domain hydrolyzed ATP with V(max) = 45 nmol mg(
      1) min(-1), similar to the full-length transporter. A Hill coefficient of 1.49
      demonstrates positive cooperativity between the two catalytic sites formed upon
      dimerization. Global fit analysis of time-resolved FTIR data revealed two
      apparent rate constants of ~1 and 0.01 s(-1), which were assigned to formation of
      the catalytic site and hydrolysis, respectively. Using isotopically labeled ATP,
      we identified specific marker bands for protein-bound ATP (1245 cm(-1)), ADP
      (1101 and 1205 cm(-1)), and free phosphate (1078 cm(-1)). Cleavage of the beta
      phosphate-gamma-phosphate bond was found to be the rate-limiting step; no protein
      bound phosphate intermediate was resolved.

PMID- 22593574
TI  - Solution structure of the IIAChitobiose-HPr complex of the N,N'
      diacetylchitobiose branch of the Escherichia coli phosphotransferase system.
AB  - The solution structure of the complex of enzyme IIA of the N,N'
      diacetylchitobiose (Chb) transporter with the histidine phosphocarrier protein
      HPr has been solved by NMR. The IIA(Chb)-HPr complex completes the structure
      elucidation of representative cytoplasmic complexes for all four sugar branches
      of the bacterial phosphoryl transfer system (PTS). The active site His-89 of
      IIA(Chb) was mutated to Glu to mimic the phosphorylated state. IIA(Chb)(H89E) and
      HPr form a weak complex with a K(D) of ~0.7 mM. The interacting binding surfaces,
      concave for IIA(Chb) and convex for HPr, complement each other in terms of shape,
      residue type, and charge distribution, with predominantly hydrophobic residues,
      interspersed by some uncharged polar residues, located centrally, and polar and
      charged residues at the periphery. The active site histidine of HPr, His-15, is
      buried within the active site cleft of IIA(Chb) formed at the interface of two
      adjacent subunits of the IIA(Chb) trimer, thereby coming into close proximity
      with the active site residue, H89E, of IIA(Chb). A His89-P-His-15 pentacoordinate
      phosphoryl transition state can readily be modeled without necessitating any
      significant conformational changes, thereby facilitating rapid phosphoryl
      transfer. Comparison of the IIA(Chb)-HPr complex with the IIA(Chb)-IIB(Chb)
      complex, as well as with other cytoplasmic complexes of the PTS, highlights a
      unifying mechanism for recognition of structurally diverse partners. This
      involves generating similar binding surfaces from entirely different underlying
      structural elements, large interaction surfaces coupled with extensive
      redundancy, and side chain conformational plasticity to optimize diverse sets of
      intermolecular interactions.

PMID- 22593575
TI  - Peroxisome Proliferator-activated receptor gamma activation by ligands and
      dephosphorylation induces proprotein convertase subtilisin kexin type 9 and low
      density lipoprotein receptor expression.
AB  - Proprotein convertase subtilisin kexin type 9 (PCSK9) plays an important role in
      cholesterol homeostasis by enhancing the degradation of LDL receptor (LDLR)
      protein. Peroxisome proliferator-activated receptor gamma (PPARgamma) has been
      shown to be atheroprotective. PPARgamma can be activated by ligands and/or
      dephosphorylation with ERK1/2 inhibitors. The effect of PPARgamma on PCSK9 and
      LDLR expression remains unknown. In this study, we investigated the effects of
      PPARgamma on PCSK9 and LDLR expression. At the cellular levels, PPARgamma ligands
      induced PCSK9 mRNA and protein expression in HepG2 cells. PCSK9 expression was
      induced by inhibition of ERK1/2 activity but inhibited by ERK1/2 activation. The
      mutagenic study and promoter activity assay suggested that the induction of PCSK9
      expression by ERK1/2 inhibitors was tightly linked to PPARgamma
      dephosphorylation. However, PPARgamma activation by ligands or ERK1/2 inhibitors
      induced hepatic LDLR expression. The promoter assay indicated that the induction
      of LDLR expression by PPARgamma was sterol regulatory element-dependent because
      PPARgamma enhanced sterol regulatory element-binding protein 2 (SREBP2)
      processing. In vivo, administration of pioglitazone or U0126 alone increased
      PCSK9 expression in mouse liver but had little effect on PCSK9 secretion.
      However, the co-treatment of pioglitazone and U0126 enhanced both PCSK9
      expression and secretion. Similar to in vitro, the increased PCSK9 expression by
      pioglitazone and/or U0126 did not result in decreased LDLR expression and
      function. In contrast, pioglitazone and/or U0126 increased LDLR protein
      expression and membrane translocation, SREBP2 processing, and CYP7A1 expression
      in the liver, which led to decreased total and LDL cholesterol levels in serum.
      Our results indicate that although PPARgamma activation increased PCSK9
      expression, PPARgamma activation induced LDLR and CYP7A1 expression that enhanced
      LDL cholesterol metabolism.

PMID- 22593576
TI  - A conserved motif in the C-terminal tail of DNA polymerase alpha tethers primase
      to the eukaryotic replisome.
AB  - The DNA polymerase alpha-primase complex forms an essential part of the
      eukaryotic replisome. The catalytic subunits of primase and pol alpha synthesize
      composite RNA-DNA primers that initiate the leading and lagging DNA strands at
      replication forks. The physical basis and physiological significance of tethering
      primase to the eukaryotic replisome via pol alpha remain poorly characterized. We
      have identified a short conserved motif at the extreme C terminus of pol alpha
      that is critical for interaction of the yeast ortholog pol1 with primase. We show
      that truncation of the C-terminal residues 1452-1468 of Pol1 abrogates the
      interaction with the primase, as does mutation to alanine of the invariant amino
      acid Phe(1463). Conversely, a pol1 peptide spanning the last 16 residues binds
      primase with high affinity, and the equivalent peptide from human Pol alpha binds
      primase in an analogous fashion. These in vitro data are mirrored by experiments
      in yeast cells, as primase does not interact in cell extracts with pol1 that
      either terminates at residue 1452 or has the F1463A mutation. The ability to
      disrupt the association between primase and pol alpha allowed us to assess the
      physiological significance of primase being tethered to the eukaryotic replisome
      in this way. We find that the F1463A mutation in Pol1 renders yeast cells
      dependent on the S phase checkpoint, whereas truncation of Pol1 at amino acid
      1452 blocks yeast cell proliferation. These findings indicate that tethering of
      primase to the replisome by pol alpha is critical for the normal action of DNA
      replication forks in eukaryotic cells.

PMID- 22593577
TI  - Diverse chemical scaffolds support direct inhibition of the membrane-bound O
      acyltransferase porcupine.
AB  - Secreted Wnt proteins constitute one of the largest families of intercellular
      signaling molecules in vertebrates with essential roles in embryonic development
      and adult tissue homeostasis. The functional redundancy of Wnt genes and the many
      forms of cellular responses they elicit, including some utilizing the
      transcriptional co-activator beta-catenin, has limited the ability of classical
      genetic strategies to uncover their roles in vivo. We had previously identified a
      chemical compound class termed Inhibitor of Wnt Production (or IWP) that targets
      Porcupine (Porcn), an acyltransferase catalyzing the addition of fatty acid
      adducts onto Wnt proteins. Here we demonstrate that diverse chemical structures
      are able to inhibit Porcn by targeting its putative active site. When deployed in
      concert with small molecules that modulate the activity of Tankyrase enzymes and
      glycogen synthase kinase 3 beta (GSK3beta), additional transducers of Wnt/beta
      catenin signaling, the IWP compounds reveal an essential role for Wnt protein
      fatty acylation in eliciting beta-catenin-dependent and -independent forms of Wnt
      signaling during zebrafish development. This collection of small molecules
      facilitates rapid dissection of Wnt gene function in vivo by limiting the
      influence of redundant Wnt gene functions on phenotypic outcomes and enables
      temporal manipulation of Wnt-mediated signaling in vertebrates.

PMID- 22593578
TI  - Molecular mechanisms of the inhibitory effects of bovine lactoferrin on
      lipopolysaccharide-mediated osteoclastogenesis.
AB  - Lactoferrin (LF) is an important modulator of the immune response and
      inflammation. It has also been implicated in the regulation of bone tissue. In
      our previous study we demonstrated that bovine LF (bLF) reduces LPS-induced bone
      resorption through a reduction of TNF-alpha production in vivo. However, it was
      not known how bLF inhibits LPS-mediated TNF-alpha and RANKL (receptor activator
      of nuclear factor kappaB ligand) production in osteoblasts. In this study we show
      that bLF impairs LPS-mediated TNF-alpha and RANKL production. bLF inhibited LPS
      mediated osteoclastogenesis via osteoblasts in a co-culture system. Furthermore,
      bLF pretreatment inhibited LPS-induced NFkappaB DNA binding activity as well as
      IkappaBalpha and IKKbeta (IkappaB kinase beta) phosphorylation. MAP kinase
      activation was also inhibited by bLF pretreatment. However, bLF pretreatment
      failed to block the degradation of IRAK1 (interleukin-1 receptor-associated
      kinase 1), which is an essential event after its activation. Remarkably, we found
      that bLF pretreatment inhibited LPS-mediated Lys-63-linked polyubiquitination of
      TNF receptor-associated factor 6 (TRAF6). We also found that bLF is mainly
      endocytosed through LRP1 (lipoprotein receptor-related protein-1) and
      intracellular distributed bLF binds to endogenous TRAF6. In addition, bLF
      inhibited IL-1beta- and flagellin-induced TRAF6-dependent activation of the
      NFkappaB signaling pathway. Collectively, our findings demonstrate that bLF
      inhibits NFkappaB and MAP kinase activation, which play critical roles in chronic
      inflammatory disease by interfering with the TRAF6 polyubiquitination process.
      Thus, bLF could be a potent therapeutic agent for inflammatory diseases
      associated with bone destruction, such as periodontitis and rheumatoid arthritis.

PMID- 22593579
TI  - Thiazolidinediones induce osteocyte apoptosis by a G protein-coupled receptor 40
      dependent mechanism.
AB  - Thiazolidinediones (TZDs) represent an interesting treatment of type 2 diabetes
      mellitus. However, adverse effects such as heart problems and bone fractures have
      already been reported. Previously, we reported that pioglitazone and
      rosiglitazone induce osteocyte apoptosis and sclerostin up-regulation; however,
      the molecular mechanisms leading to such effects are unknown. In this study, we
      found that TZDs rapidly activated Erk1/2 and p38. These activations were mediated
      through Ras proteins and GPR40, a receptor expressed on the surface of
      osteocytes. Activation of this pathway led only to osteocyte apoptosis but not
      sclerostin up-regulation. On the other hand, TZDs were capable of activating
      peroxisome proliferator-activated receptor-gamma, and activation of this
      signaling pathway led to sclerostin up-regulation but not osteocyte apoptosis.
      This study demonstrates two distinct signaling pathways activated in osteocytes
      in response to TZDs that could participate in the observed increase in fractures
      in TZD-treated patients.

PMID- 22593580
TI  - Structural insights into the substrate specificity of Streptococcus pneumoniae
      beta(1,3)-galactosidase BgaC.
AB  - The surface-exposed beta-galactosidase BgaC from Streptococcus pneumoniae was
      reported to be a virulence factor because of its specific hydrolysis activity
      toward the beta(1,3)-linked galactose and N-acetylglucosamine (Galbeta(1,3)NAG)
      moiety of oligosaccharides on the host molecules. Here we report the crystal
      structure of BgaC at 1.8 A and its complex with galactose at 1.95 A. At pH 5.5
      8.0, BgaC exists as a stable homodimer, each subunit of which consists of three
      distinct domains: a catalytic domain of a classic (beta/alpha)(8) TIM barrel,
      followed by two all-beta domains (ABDs) of unknown function. The side walls of
      the TIM beta-barrel and a loop extended from the first ABD constitute the active
      site. Superposition of the galactose-complexed structure to the apo-form revealed
      significant conformational changes of residues Trp-243 and Tyr-455. Simulation of
      a putative substrate entrance tunnel and modeling of a complex structure with
      Galbeta(1,3)NAG enabled us to assign three key residues to the specific
      catalysis. Site-directed mutagenesis in combination with activity assays further
      proved that residues Trp-240 and Tyr-455 contribute to stabilizing the N
      acetylglucosamine moiety, whereas Trp-243 is critical for fixing the galactose
      ring. Moreover, we propose that BgaC and other galactosidases in the GH-35 family
      share a common domain organization and a conserved substrate-determinant aromatic
      residue protruding from the second domain.

PMID- 22593581
TI  - Structure and conservation of the periplasmic targeting factor Tic22 protein from
      plants and cyanobacteria.
AB  - Mitochondria and chloroplasts are of endosymbiotic origin. Their integration into
      cells entailed the development of protein translocons, partially by recycling
      bacterial proteins. We demonstrate the evolutionary conservation of the
      translocon component Tic22 between cyanobacteria and chloroplasts. Tic22 in
      Anabaena sp. PCC 7120 is essential. The protein is localized in the thylakoids
      and in the periplasm and can be functionally replaced by a plant orthologue.
      Tic22 physically interacts with the outer envelope biogenesis factor Omp85 in
      vitro and in vivo, the latter exemplified by immunoprecipitation after chemical
      cross-linking. The physical interaction together with the phenotype of a tic22
      mutant comparable with the one of the omp85 mutant indicates a concerted function
      of both proteins. The three-dimensional structure allows the definition of
      conserved hydrophobic pockets comparable with those of ClpS or BamB. The results
      presented suggest a function of Tic22 in outer membrane biogenesis.

PMID- 22593582
TI  - Oligomer size of the serotonin 5-hydroxytryptamine 2C (5-HT2C) receptor revealed
      by fluorescence correlation spectroscopy with photon counting histogram analysis:
      evidence for homodimers without monomers or tetramers.
AB  - Fluorescence correlation spectroscopy (FCS) and photon counting histogram (PCH)
      are techniques with single molecule sensitivity that are well suited for
      examining the biophysical properties of protein complexes in living cells. In the
      present study, FCS and PCH were applied to determine the diffusion coefficient
      and oligomeric size of G-protein-coupled receptors. FCS was used to record
      fluctuations in fluorescence intensity arising from fluorescence-tagged 5
      hydroxytryptamine 2C (5-HT(2C)) receptors diffusing within the plasma membrane of
      HEK293 cells and rat hippocampal neurons. Autocorrelation analysis yielded
      diffusion coefficients ranging from 0.8 to 1.2 MUm(2)/s for fluorescence-tagged
      receptors. Because the molecular brightness of a fluorescent protein is directly
      proportional to the number of fluorescent proteins traveling together within a
      protein complex, it can be used to determine the oligomeric size of the protein
      complex. FCS and PCH analysis of fluorescence-tagged 5-HT(2C) receptors provided
      molecular brightness values that were twice that of GFP and YFP monomeric
      controls, similar to a dimeric GFP control, and unaltered by 5-HT. Bimolecular
      fluorescence complementation of the N- and C-terminal halves of YFP attached to 5
      HT(2C) receptors was observed in endoplasmic reticulum/Golgi and plasma membranes
      with a brightness equal to monomeric YFP. When GFP-tagged 5-HT(2C) receptors were
      co-expressed with a large excess of untagged, non-fluorescent 5-HT(2C) receptors,
      the molecular brightness was reduced by half. PCH analysis of the FCS data were
      best described by a one-component dimer model without monomers or tetramers.
      Therefore, it is concluded that 5-HT(2C) receptors freely diffusing within the
      plasma membrane are dimeric.

PMID- 22593583
TI  - Carbon monoxide mediates the anti-apoptotic effects of heme oxygenase-1 in
      medulloblastoma DAOY cells via K+ channel inhibition.
AB  - Tumor cell survival and proliferation is attributable in part to suppression of
      apoptotic pathways, yet the mechanisms by which cancer cells resist apoptosis are
      not fully understood. Many cancer cells constitutively express heme oxygenase-1
      (HO-1), which catabolizes heme to generate biliverdin, Fe(2+), and carbon
      monoxide (CO). These breakdown products may play a role in the ability of cancer
      cells to suppress apoptotic signals. K(+) channels also play a crucial role in
      apoptosis, permitting K(+) efflux which is required to initiate caspase
      activation. Here, we demonstrate that HO-1 is constitutively expressed in human
      medulloblastoma tissue, and can be induced in the medulloblastoma cell line DAOY
      either chemically or by hypoxia. Induction of HO-1 markedly increases the
      resistance of DAOY cells to oxidant-induced apoptosis. This effect was mimicked
      by exogenous application of the heme degradation product CO. Furthermore we
      demonstrate the presence of the pro-apoptotic K(+) channel, Kv2.1, in both human
      medulloblastoma tissue and DAOY cells. CO inhibited the voltage-gated K(+)
      currents in DAOY cells, and largely reversed the oxidant-induced increase in K(+)
      channel activity. p38 MAPK inhibition prevented the oxidant-induced increase of
      K(+) channel activity in DAOY cells, and enhanced their resistance to apoptosis.
      Our findings suggest that CO-mediated inhibition of K(+) channels represents an
      important mechanism by which HO-1 can increase the resistance to apoptosis of
      medulloblastoma cells, and support the idea that HO-1 inhibition may enhance the
      effectiveness of current chemo- and radiotherapies.

PMID- 22593584
TI  - A highly conserved cytoplasmic cysteine residue in the alpha4 nicotinic
      acetylcholine receptor is palmitoylated and regulates protein expression.
AB  - Nicotinic acetylcholine receptor (nAChR) cell surface expression levels are
      modulated during nicotine dependence and multiple disorders of the nervous
      system, but the mechanisms underlying nAChR trafficking remain unclear. To
      determine the role of cysteine residues, including their palmitoylation, on
      neuronal alpha4 nAChR subunit maturation and cell surface trafficking, the
      cysteines in the two intracellular regions of the receptor were replaced with
      serines using site-directed mutagenesis. Palmitoylation is a post-translational
      modification that regulates membrane receptor trafficking and function. Metabolic
      labeling with [(3)H]palmitate determined that the cysteine in the cytoplasmic
      loop between transmembrane domains 1 and 2 (M1-M2) is palmitoylated. When this
      cysteine is mutated to a serine, producing a depalmitoylated alpha4 nAChR, total
      protein expression decreases, but surface expression increases compared with wild
      type alpha4 levels, as determined by Western blotting and enzyme-linked
      immunoassays, respectively. The cysteines in the M3-M4 cytoplasmic loop do not
      appear to be palmitoylated, but replacing all of the cysteines in the loop with
      serines increases total and cell surface expression. When all of the
      intracellular cysteines in both loops are mutated to serines, there is no change
      in total expression, but there is an increase in surface expression. Calcium
      accumulation assays and high affinity binding for [(3)H]epibatidine determined
      that all mutants retain functional activity. Thus, our results identify a novel
      palmitoylation site on cysteine 273 in the M1-M2 loop of the alpha4 nAChR and
      determine that cysteines in both intracellular loops are regulatory factors in
      total and cell surface protein expression of the alpha4beta2 nAChR.

PMID- 22593585
TI  - A network of ubiquitin ligases is important for the dynamics of misfolded protein
      aggregates in yeast.
AB  - Quality control ubiquitin ligases promote degradation of misfolded proteins by
      the proteasome. If the capacity of the ubiquitin/proteasome system is exceeded,
      then misfolded proteins accumulate in aggregates that are cleared by the
      autophagic system. To identify components of the ubiquitin/proteasome system that
      protect against aggregation, we analyzed a GFP-tagged protein kinase,
      Ste11DeltaN(K444R)-GFP, in yeast strains deleted for 14 different ubiquitin
      ligases. We show that deletion of almost all of these ligases affected the
      proteostatic balance in untreated cells such that Ste11DeltaN(K444R)-GFP
      aggregation was changed significantly compared with the levels found in wild type
      cells. By contrast, aggregation was increased significantly in only six E3
      deletion strains when Ste11DeltaN(K444R)-GFP folding was impaired due to
      inhibition of the molecular chaperone Hsp90 with geldanamycin. The increase in
      aggregation of Ste11DeltaN(K444R)-GFP due to deletion of UBR1 and UFD4 was
      partially suppressed by deletion of UBR2 due to up-regulation of Rpn4, which
      controls proteasome activity. Deletion of UBR1 in combination with LTN1, UFD4, or
      DOA10 led to a marked hypersensitivity to azetidine 2-carboxylic acid, suggesting
      some redundancy in the networks of quality control ubiquitin ligases. Finally, we
      show that Ubr1 promotes clearance of protein aggregates when the autophagic
      system is inactivated. These results provide insight into the mechanics by which
      ubiquitin ligases cooperate and provide feedback regulation in the clearance of
      misfolded proteins.

PMID- 22593586
TI  - MicroRNA-143 (miR-143) regulates cancer glycolysis via targeting hexokinase 2
      gene.
AB  - High glycolysis, well known as "Warburg effect," is frequently observed in a
      variety of cancers. Whether the deregulation of miRNAs contributes to the Warburg
      effect remains largely unknown. Because miRNA regulates gene expression at both
      mRNA and protein levels, we constructed a gene functional association network,
      which allows us to detect the gene activity instead of gene expression, to
      integratively analyze the microarray data for gene expression and miRNA
      expression profiling and identify glycolysis-related gene-miRNA pairs deregulated
      in cancer. Hexokinase 2 (HK2), coding for the first rate-limiting enzyme of
      glycolysis, is among the top list of genes predicted and potentially regulated by
      multiple miRNAs including miR-143. Interestingly, miR-143 expression was
      inversely associated with HK2 protein level but not mRNA level in human lung
      cancer samples. miR-143, down-regulated by mammalian target of rapamycin
      activation, reduces glucose metabolism and inhibits cancer cell proliferation and
      tumor formation through targeting HK2. Collectively, we have not only established
      a novel methodology for gene-miRNA pair prediction but also identified miR-143 as
      an essential regulator of cancer glycolysis via targeting HK2.

PMID- 22593587
TI  - Brown adipose tissue and its relationship to bone structure in pediatric
      patients.
AB  - CONTEXT: Emerging evidence suggests a possible link between brown adipose tissue
      (BAT) and bone metabolism. OBJECTIVE: The objective of this study was to examine
      the relationships between BAT and bone cross-sectional dimensions in children and
      adolescents. DESIGN: This was a cross-sectional study. SETTING: The study was
      conducted at a pediatric referral center. PATIENTS: Patients included 40 children
      and teenagers (21 males and 19 females) successfully treated for pediatric
      malignancies. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES:
      The volume of BAT was determined by fluorodeoxyglucose-positron emission
      tomography/computed tomography. Measures of the cross-sectional area and cortical
      bone area and measures of thigh musculature and sc fat were determined at the
      midshaft of the femur. RESULTS: Regardless of sex, there were significant
      correlations seen between BAT volume and the cross-sectional dimensions of the
      bone (r values between 0.68 and 0.77; all P <= 0 .001). Multiple regression
      analyses indicated that the volume of BAT predicted femoral cross-sectional area
      and cortical bone area, even after accounting for height, weight, and gender. The
      addition of muscle as an independent variable increased the predictive power of
      the model but significantly decreased the contribution of BAT. CONCLUSIONS: The
      volume of BAT is positively associated with the amount of bone and the cross
      sectional size of the femur in children and adolescents. This relation between
      BAT and bone structure could, at least in part, be mediated by muscle.

PMID- 22593588
TI  - Parental origin of the X-chromosome does not influence growth hormone treatment
      effect in Turner syndrome.
AB  - CONTEXT: The parental origin of the intact X-chromosome has been reported to
      affect phenotype and response to GH treatment in Turner syndrome (TS). OBJECTIVE:
      Our objective was to evaluate the influence of the parental origin of the X
      chromosome on body growth and GH treatment effect in TS. DESIGN AND SETTING: We
      conducted a population-based cohort study of TS patients previously treated with
      GH. PARTICIPANTS: Participants included patients with a nonmosaic 45,X karyotype;
      556 women were identified as eligible, 233 (49%) of whom participated, together
      with their mothers. Data were analyzed for 180 of these patients. MAIN OUTCOME
      MEASURES: We performed fluorescence in situ hybridization analysis to exclude
      mosaicism and microsatellite analysis of nine polymorphic markers in DNA from the
      patients and their mothers. The influence on growth and effect of GH were
      analyzed by univariate and multivariate methods. RESULTS: The X-chromosome was of
      paternal origin (X(pat)) in 52 (29%) of 180 and of maternal origin (X(mat)) in
      128 (71%) of 180 patients. Height gain from the start of GH treatment to adult
      height was similar in X(mat) and X(pat) patients (+2.1 +/- 0.9 vs. +2.2 +/- 0.8
      TS sd score, P = 0.45). The lack of influence of parental origin of the X
      chromosome was confirmed in multivariate analysis. Parental origin of the X
      chromosome also had no effect on the other growth characteristics studied,
      including growth velocity during the first year on GH treatment. Patient height
      was correlated with the heights of both parents and was not influenced by the
      parental origin of the X-chromosome. CONCLUSION: In this, the largest such study
      carried out to date, the parental origin of the X-chromosome did not alter the
      effect of GH treatment or affect any other features of growth in TS.

PMID- 22593589
TI  - Adolescent fiber consumption is associated with visceral fat and inflammatory
      markers.
AB  - CONTEXT: The link between adolescent fiber consumption, inflammation, and body
      fat distribution has not been investigated. OBJECTIVE: This study investigated
      associations of dietary fiber intake with inflammatory-related biomarkers and
      robust measures of total and central adiposity in a sample of 559 adolescents
      aged 14-18 yr (49% female, 45% Black). METHODS: Fasting blood samples were
      measured for leptin, adiponectin, resistin, C-reactive protein, and fibrinogen.
      Diet was assessed with four to seven 24-h recalls, and physical activity was
      determined by accelerometry. Fat-free soft tissue mass and fat mass were measured
      by dual-energy x-ray absorptiometry. Visceral adipose tissue was assessed using
      magnetic resonance imaging. RESULTS: Multiple linear regression, adjusting for
      age, race, Tanner stage, fat-free soft tissue mass, energy intake, and physical
      activity, revealed that dietary fiber intake was inversely associated with fat
      mass and serum leptin in males (all P < 0.03) but not in females. In both
      genders, dietary fiber intake was negatively associated with visceral adipose
      tissue, plasma C-reactive protein, and plasma fibrinogen and positively
      associated with plasma adiponectin (all P < 0.05). No relations were found
      between dietary fiber intake and plasma resistin in either males or females.
      CONCLUSION: Our adolescent data suggest that greater consumption of dietary fiber
      is associated with lower visceral adiposity and multiple biomarkers implicated in
      inflammation.

PMID- 22593590
TI  - Combination treatment with T4 and T3: toward personalized replacement therapy in
      hypothyroidism?
AB  - CONTEXT: Levothyroxine therapy is the traditional lifelong replacement therapy
      for hypothyroid patients. Over the last several years, new evidence has led
      clinicians to evaluate the option of combined T(3) and T(4) treatment to improve
      the quality of life, cognition, and peripheral parameters of thyroid hormone
      action in hypothyroidism. The aim of this review is to assess the physiological
      basis and the results of current studies on this topic. EVIDENCE ACQUISITION: We
      searched Medline for reports published with the following search terms:
      hypothyroidism, levothyroxine, triiodothyronine, thyroid, guidelines, treatment,
      deiodinases, clinical symptoms, quality of life, cognition, mood, depression,
      body weight, heart rate, cholesterol, bone markers, SHBG, and patient preference
      for combined therapy. The search was restricted to reports published in English
      since 1970, but some reports published before 1970 were also incorporated. We
      supplemented the search with records from personal files and references of
      relevant articles and textbooks. Parameters analyzed included the rationale for
      combination treatment, the type of patients to be selected, the optimal T(4)/T(3)
      ratio, and the potential benefits of this therapy on symptoms of hypothyroidism,
      quality of life, mood, cognition, and peripheral parameters of thyroid hormone
      action. EVIDENCE SYNTHESIS: The outcome of our analysis suggests that it may be
      time to consider a personalized regimen of thyroid hormone replacement therapy in
      hypothyroid patients. CONCLUSIONS: Further prospective randomized controlled
      studies are needed to clarify this important issue. Innovative formulations of
      the thyroid hormones will be required to mimic a more perfect thyroid hormone
      replacement therapy than is currently available.

PMID- 22593591
TI  - Remarkable cystic expansion of microprolactinoma causing diabetes insipidus
      during pregnancy.

PMID- 22593592
TI  - Mesothelioma of the tunica vaginalis with BerEp4 and LeuM1 expression:
      identification of cytoplasmic tonofilaments by electron microscopy is a key
      diagnostic feature.

PMID- 22593593
TI  - Population snapshot of invasive serogroup B meningococci in South Africa from
      2005 to 2008.
AB  - In South Africa, serogroup B meningococcal disease is sporadic. The aim of this
      study was to characterize serogroup B strains causing invasive meningococcal
      disease (IMD) in South Africa from 2005 to 2008. Isolates, collected through a
      national, laboratory-based surveillance program for IMD, were characterized by
      multilocus sequence typing (MLST). Two thousand two hundred thirty-four cases
      were reported, of which 1,447 had viable isolates. Intermediate resistance to
      penicillin was observed in 2.8% (41/1,447) of all strains. Serogroup B was the
      second most common serogroup (17%, 251/1,447) and increased from 14% (58/414) in
      2005 to 25% (72/290) in 2008 (P < 0.001); however, incidence remained stable
      during the study period (average incidence, 0.13/100,000 population) (P = 0.54).
      Serogroup B was predominantly characterized by three clonal complexes, namely, ST
      41/44/lineage 3, ST-32/ET-5, and the new complex ST-4240/6688, which accounted
      for 27% (65/242), 23% (55/242), and 16% (38/242) of isolates, respectively. ST
      4240/6688 was more prevalent among young children (<5 years) than other clonal
      complexes (27/37 [73%] versus 108/196 [55%]; P = 0.04). In the most densely
      populated province of South Africa, Gauteng, the prevalence of ST-32/ET-5
      increased from 8% (2/24) in 2005 to 38% (9/24) in 2008 (P = 0.04). Capsular
      switching was observed in 8/242 (3%) strains. The newly assigned clonal complex
      ST-4240/6688 was more common in young children.

PMID- 22593594
TI  - Corynebacterium tuberculostearicum: a potentially misidentified and
      multiresistant Corynebacterium species isolated from clinical specimens.
AB  - Corynebacterium tuberculostearicum is a lipophilic corynebacterium validly
      characterized in 2004. We provide clinical information on 18 patients from whom
      this organism was isolated. The majority of the patients were hospitalized and
      had a history of prolonged treatment with broad-spectrum antimicrobials. In 7
      (38.9%) of the 18 cases, the isolates were found to be clinically relevant. The
      present report also includes detailed data on the biochemical and molecular
      identification of C. tuberculostearicum, as well as its identification by matrix
      assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF
      MS). Our data demonstrate that routine biochemical tests do not provide reliable
      identification of C. tuberculostearicum. MALDI-TOF MS represents a helpful tool
      for the identification of this species, since all of the strains matched C.
      tuberculostearicum as the first choice and 58.3% (7/12) of the strains processed
      with the full extraction protocol generated scores of >2.000. Nevertheless,
      partial 16S rRNA gene sequencing still represents the gold standard for the
      identification of this species. Due to the challenging identification of C.
      tuberculostearicum, we presume that this organism is often misidentified and its
      clinical relevance is underestimated. The antimicrobial susceptibility profile of
      C. tuberculostearicum presented here reveals that 14 (87.5%) of the 16 strains
      analyzed exhibited multidrug resistance.

PMID- 22593595
TI  - Relationship between vancomycin-resistant Staphylococcus aureus, vancomycin
      intermediate S. aureus, high vancomycin MIC, and outcome in serious S. aureus
      infections.
AB  - Vancomycin has been used successfully for over 50 years for the treatment of
      Staphylococcus aureus infections, particularly those involving methicillin
      resistant S. aureus. It has proven remarkably reliable, but its efficacy is now
      being questioned with the emergence of strains of S. aureus that display
      heteroresistance, intermediate resistance, and, occasionally, complete vancomycin
      resistance. More recently, an association has been established between poor
      outcome and infections with strains of S. aureus with an elevated vancomycin MIC
      within the susceptible range. This minireview summarizes the definitions,
      mechanisms, clinical impact, and laboratory identification of reduced vancomycin
      susceptibility in S. aureus and discusses practical issues for the diagnostic
      laboratory in testing and interpreting vancomycin susceptibility for S. aureus
      infections.

PMID- 22593596
TI  - Performances of the Vitek MS matrix-assisted laser desorption ionization-time of
      flight mass spectrometry system for rapid identification of bacteria in routine
      clinical microbiology.
AB  - Rapid and cost-effective matrix-assisted laser desorption ionization-time of
      flight mass spectrometry (MALDI-TOF MS)-based systems will replace conventional
      phenotypic methods for routine identification of bacteria. We report here the
      first evaluation of the new MALDI-TOF MS-based Vitek MS system in a large
      clinical microbiology laboratory. This system uses an original spectrum
      classifier algorithm and a specific database designed for the identification of
      clinically relevant species. We have tested 767 routine clinical isolates
      representative of 50 genera and 124 species. Vitek MS-based identifications were
      performed by means of a single deposit on a MALDI disposable target without any
      prior extraction step and compared with reference identifications obtained mainly
      with the VITEK2 phenotypic system; if the identifications were discordant,
      molecular techniques provided reference identifications. The Vitek MS system
      provided 96.2% correct identifications to the species level (86.7%), to the genus
      level (8.2%), or within a range of species belonging to different genera (1.3%).
      Conversely, 1.3% of isolates were misidentified and 2.5% were unidentified,
      partly because the species was not included in the database; a second deposit
      provided a successful identification for 0.8% of isolates unidentified with the
      first deposit. The Vitek MS system is a simple, convenient, and accurate method
      for routine bacterial identification with a single deposit, considering the high
      bacterial diversity studied and as evidenced by the low prevalence of species
      without correct identification. In addition to a second deposit in uncommon
      cases, expanding the spectral database is expected to further enhance
      performances.

PMID- 22593597
TI  - Molecular epidemiologic analysis and antimicrobial resistance of Helicobacter
      cinaedi isolated from seven hospitals in Japan.
AB  - Helicobacter cinaedi colonizes the colons of human and animals and can cause
      colitis, cellulitis, and sepsis in humans, with infections in immunocompromised
      patients being increasingly recognized. However, methods for analyzing the
      molecular epidemiology of H. cinaedi are not yet established. A genotyping method
      involving multilocus sequence typing (MLST) was developed and used to analyze 50
      H. cinaedi isolates from Japanese hospitals in addition to 6 reference strains.
      Pulsed-field gel electrophoresis (PFGE) results were also compared with the MLST
      results. Based on the genomic information from strain CCUG18818, 21 housekeeping
      genes were selected as candidates for MLST and were observed to have high
      homology (96.5 to 100%) between isolates. Following a comparison of the 21
      housekeeping genes from 8 H. cinaedi isolates, 7 genes were chosen for MLST,
      revealing 14 sequence types (STs). The isolates from 3 hospitals belonged to the
      same STs, but the isolates from the other 4 hospitals belonged to different STs.
      Isolates belonging to ST6 were analyzed by PFGE and showed similar, but not
      identical, patterns between isolates. Isolates belonging to ST9, ST10, and ST11,
      which belonged to the same clonal complex, had the same pattern. All isolates
      were found to contain mutations in GyrA and the 23S rRNA gene that confer
      ciprofloxacin and clarithromycin resistance, respectively, in H. cinaedi. These
      results raise concerns about the increase in H. cinaedi isolates resistant to
      clarithromycin and ciprofloxacin in Japan.

PMID- 22593598
TI  - Prognostic value of indeterminate IFN-gamma release assay results in HIV-1
      infection.
AB  - In this prospective, longitudinal study on 948 HIV-1-infected patients, subjects
      with an indeterminate IFN-gamma (gamma interferon) release assay (IGRA) result at
      baseline were at significantly higher risk of developing AIDS-defining
      manifestations other than tuberculosis (TB) irrespective of CD4(+) T cell count.
      Thus, in HIV-1-infected patients with advanced quantitative CD4(+) T cell
      depletion, an indeterminate IGRA might indicate an additional loss of global T
      cell function, warranting detailed clinical evaluation and careful follow-up.

PMID- 22593599
TI  - Identification of DNA signatures suitable for use in development of real-time PCR
      assays by whole-genome sequence approaches: use of Streptococcus pyogenes in a
      pilot study.
AB  - A stepwise computational approach using three layers of publicly available
      software was found to effectively identify DNA signatures for Streptococcus
      pyogenes. PCR testing validated that 9 out of 15 signature-derived primer sets
      could detect as low as 5 fg of target DNA with high specificity. The selected
      signature-derived primer sets were successfully evaluated against all 23 clinical
      isolates. The approach is readily applicable for designing molecular assays for
      rapid detection and characterization of various pathogenic bacteria.

PMID- 22593600
TI  - A novel extraction method combining plasma with a whole-blood fraction shows
      excellent sensitivity and reproducibility for patients at high risk for invasive
      aspergillosis.
AB  - Diagnosis of invasive aspergillosis (IA) is still a major problem in routine
      clinical practice. Early diagnosis is essential for a good patient prognosis. PCR
      is a highly sensitive method for the detection of nucleic acids and could play an
      important role in improving the diagnosis of fungal infections. Therefore, a
      novel DNA extraction method, ultraclean production (UCP), was developed allowing
      purification of both cellular and cell-free circulating fungal DNA. In this
      prospective study we evaluated the commercially available UCP extraction system
      and compared it to an in-house system. Sixty-three patients at high risk for IA
      were screened twice weekly, and DNA extracted by both methods was cross-analyzed,
      in triplicate, by two different real-time PCR assays. The negative predictive
      values were high for all methods (94.3 to 100%), qualifying them as screening
      methods, but the sensitivity and diagnostic odds ratios were higher using the UCP
      extraction method. Sensitivity ranged from 33.3 to 66.7% using the in-house
      extracts to 100% using the UCP extraction method. Most of the unclassified
      patients showed no positive PCR results; however, single-positive PCR replicates
      were observed in some cases. These can bear clinical relevance but should be
      interpreted with additional clinical and laboratory data. The PCR assays from the
      UCP extracts showed greater reproducibility than the in-house method for probable
      IA patients. The standardized UCP extraction method yielded superior results,
      with regard to sensitivity and reproducibility, than the in-house method. This
      was independent of the PCR assay used to detect fungal DNA in the sample
      extracts.

PMID- 22593601
TI  - Limited usefulness of microsatellite markers from the malaria vector Anopheles
      gambiae when applied to the closely related species Anopheles melas.
AB  - Anopheles melas is a brackish water mosquito found in coastal West Africa where
      it is a dominant malaria vector locally. In order to facilitate genetic studies
      of this species, 45 microsatellite loci originally developed for Anopheles
      gambiae were sequenced in An. melas. Those that were suitable based on repeat
      number and flanking regions were examined in 2 natural populations from
      Equatorial Guinea. Only 15 loci were eventually deemed suitable as polymorphic
      markers in An. melas populations. These loci were screened in 4 populations from
      a wider geographic range. Heterozygosity estimates ranged from 0.18 to 0.79, and
      2.5-15 average alleles were observed per locus, yielding 13 highly polymorphic
      markers and 2 loci with lower variability. To examine the usefulness of
      microsatellite markers when applied in a sibling species, the original An.
      gambiae specific markers were used to amplify 5 loci in An. melas. Null alleles
      were found for 1 An. gambiae marker. We discuss the pitfalls of using
      microsatellite loci across closely related species and conclude that in addition
      to the problem of null alleles associated with this practice, many loci may prove
      to be of very limited use as polymorphic markers even when used in a sibling
      species.

PMID- 22593602
TI  - Do time, heterochromatin, NORs, or chromosomal rearrangements correlate with
      distribution of interstitial telomeric repeats in Sigmodon (cotton rats)?
AB  - We studied the chromosomal distribution of telomere repeats (TTAGGG)(n) in 8
      species of Sigmodon (cotton rats) using chromosome paints fluorescent in situ
      hybridization (FISH) from Sigmodon hispidus. In 2 species with the proposed
      primitive karyotype for the genus, telomere repeats were restricted to telomeric
      sites. But in the other 6 species that include 3 with proposed primitive
      karyotypes and 3 with highly rearranged karyotypes, telomere repeats were found
      on both telomeric sites and within interstitial telomeric sites (ITSs). To
      explain the distribution of ITS in Sigmodon, we gather data from C-bands, silver
      nitrate staining, G-bands, and chromosomal paint data from previous published
      studies. We did find some correlation with ITS and heterochromatin, euchromatic
      chromosomal rearrangements, and nucleolar organizing regions. No one type of
      chromosomal structure explains all ITS in Sigmodon. Multiple explanations and
      mechanisms for movement of intragenomic sequences are required to explain ITS in
      this genus. We rejected the hypothesis that age of a lineage correlates with the
      presence of ITS using divergence time estimate analyses. This multigene phylogeny
      places species with ITS (S. arizonae, S. fulviventer, S. hispidus, S.
      mascotensis, S. ochrognathus, and S. toltecus) in the clade with a species
      without ITS (S. hirsutus). Lineages with ITS (S. arizonae and S. mascotensis)
      arose independently from a lineage absent of ITS (S. hirsutus) around 0.67 to
      0.83 Ma. The rearranged karyotypes of S. mascotensis and S. arizonae appear to be
      an independently derived autapomorphic characters, supporting a fast rate of
      chromosomal changes that vary among species.

PMID- 22593603
TI  - Recent Advancements in the LC- and GC-Based Analysis of Malondialdehyde (MDA): A
      Brief Overview.
AB  - Malondialdehyde (MDA) is an end-product of lipid peroxidation and a side product
      of thromboxane A(2) synthesis. Moreover, it is not only a frequently measured
      biomarker of oxidative stress, but its high reactivity and toxicity underline the
      fact that this molecule is more than "just" a biomarker. Additionally, MDA was
      proven to be a mutagenic substance. Having said this, it is evident that there is
      a major interest in the highly selective and sensitive analysis of this molecule
      in various matrices. In this review, we will provide a brief overview of the most
      recent developments and techniques for the liquid chromatography (LC) and gas
      chromatography (GC)-based analysis of MDA in different matrices. While the 2
      thiobarbituric acid assay still is the most prominent methodology for determining
      MDA, several advanced techniques have evolved, including GC-MS(MS), LC-MS(MS) as
      well as several derivatization-based strategies.

PMID- 22593604
TI  - Quantification of Lipophilicity of 1,2,4-Triazoles Using Micellar Chromatography.
AB  - High-performance liquid chromatography (HPLC), over-pressured-layer
      chromatography (OPLC) and thin-layer chromatography (TLC) techniques with
      micellar mobile phases were proposed to evaluate the lipophilicity of 21 newly
      synthesized 1,2,4-triazoles, compounds of potential importance in medicine or
      agriculture as fungicides. Micellar parameters log k(m) were compared with
      extrapolated R(M0) values determined from reversed-phase (RP) TLC experimental
      data obtained on RP-8 stationary phases as well as with log P values (Alog Ps,
      AClog P, Alog P, Mlog P, KowWin, xlog P2 and xlog P3) calculated from molecular
      structures of solutes tested. The results obtained by applying principal
      component analysis (PCA) and linear regression showed considerable similarity
      between partition and retention parameters as alternative lipophilicity
      descriptors, and indicated micellar chromatography as a suitable technique to
      study lipophilic properties of organic substances. In micellar HPLC, RP-8e column
      (Purospher) was applied, whereas in OPLC and TLC, RP-CN plates were applied,
      which was the novelty of this study and allowed the use of micellar effluents in
      planar chromatography measurements.

PMID- 22593605
TI  - Pt-catalyzed cyclization/migration of propargylic alcohols for the synthesis of
      3(2H)-furanones, pyrrolones, indolizines, and indolizinones.
AB  - Several heterocycles such as furanones, pyrrolones, and indolizines, which are of
      pharmacological importance, are easily accessed via the Pt(II)-catalyzed
      heterocyclization/1,2-migration of propargylic ketols or hydroxy imine
      derivatives. This method sidesteps the challenges of traditional heteroaromatic
      oxygenation strategies such as regioselectivity and functional group tolerance in
      the syntheses of these heterocycles.

PMID- 22593606
TI  - Biological Removal of Azo and Triphenylmethane Dyes and Toxicity of Process By
      Products.
AB  - Increasing environmental pollution is connected with broad applications of dyes
      and imperfection of dyeing technology. Decolourization of triphenylmethane
      brilliant green and disazo Evans blue by bacterial and fungal strains and
      toxicity (phyto- and zootoxicity) of degradation by-products were investigated.
      Influence of incubation method on dyes removal was evaluated (static, semi
      static, shaken). Dead biomass was used for sorption estimation. Toxicity of
      treated dyes was measured to estimate possible influence on aquatic ecosystems.
      The zootoxicity test was done with Daphnia magna and phytotoxicity with Lemna
      minor. Samples were classified according to ACE 89/BE 2/D3 Final Report
      Commission EC. The best results of removal for all tested strains were reached in
      shaken samples. In opposite to fungi, bacterial strains decolourized brilliant
      green more effectively than Evans blue. The most effective bacterial strain was
      Erwinia spp. (s12) and fungal strains were Polyporus picipes (RWP17) and
      Pleurotus ostreatus (BWPH and MB). Decolourization of brilliant green was
      connected with decrease of zootoxicity (D. magna) and phytotoxicity (L. minor).
      Removal of Evans blue was connected with no changes in zootoxicity and decrease
      of phytotoxicity in most of samples.

PMID- 22593607
TI  - Biological Denitrification of High Nitrate Processing Wastewaters from Explosives
      Production Plant.
AB  - Wastewater samples originating from an explosives production plant (3,000 mg N l(
      1) nitrate, 4.8 mg l(-1) nitroglycerin, 1.9 mg l(-1) nitroglycol and 1,200 mg l(
      1) chemical oxygen demand) were subjected to biological purification. An attempt
      to completely remove nitrate and to decrease the chemical oxygen demand was
      carried out under anaerobic conditions. A soil isolated microbial consortium
      capable of biodegrading various organic compounds and reduce nitrate to
      atmospheric nitrogen under anaerobic conditions was used. Complete removal of
      nitrates with simultaneous elimination of nitroglycerin and ethylene glycol
      dinitrate (nitroglycol) was achieved as a result of the conducted research.
      Specific nitrate reduction rate was estimated at 12.3 mg N g(-1) VSS h(-1).
      Toxicity of wastewater samples during the denitrification process was studied by
      measuring the activity of dehydrogenases in the activated sludge. Mutagenicity
      was determined by employing the Ames test. The maximum mutagenic activity did not
      exceed 0.5. The obtained results suggest that the studied wastewater samples did
      not exhibit mutagenic properties.

PMID- 22593608
TI  - Mechanisms for Translocation of Heavy Metals from Soil to Epigeal Mosses.
AB  - The mechanisms for translocation of heavy metals from soil to epigeal mosses were
      investigated. The first mechanism was demonstrated for (137)Cs and involved the
      uplifting of the pollutant-containing dust from the soil, followed by the local
      secondary deposition on surfaces of epigeal mosses and epiphytic lichens. The
      second mechanism involved the diffusion of metal cations from the soil through
      water wetting the moss into the gametophyte. The mechanism was demonstrated by
      measuring the electric conductance of wetted gametophytes with single ends
      immersed in solutions of Cu and Na salts. In addition, the concentrations of Cu
      and Cd were compared in moss samples exposed to the natural soil and to the soil
      contaminated with the metals. The exposition to the contaminated soil resulted in
      the statistically significant increase of metal concentrations in the
      gametophytes.

PMID- 22593609
TI  - Self-Determination Theory and Motivational Interviewing: Complementary Models to
      Elicit Voluntary Engagement by Partner-Abusive Men.
AB  - Research examining intimate partner violence (IPV) has lacked a comprehensive
      theoretical framework for understanding and treating behavior. The authors
      propose two complementary models, a treatment approach (Motivational
      Interviewing, MI) informed by a theory (Self-Determination Theory; SDT), as a way
      of integrating existing knowledge and suggesting new directions in intervening
      early with IPV perpetrators. MI is a client-centered clinical intervention
      intended to assist in strengthening motivation to change and has been widely
      implemented in the substance abuse literature. SDT is a theory that focuses on
      internal versus external motivation and considers elements that impact optimal
      functioning and psychological well-being. These elements include psychological
      needs, integration of behavioral regulations, and contextual influences on
      motivation. Each of these aspects of SDT is described in detail and in the
      context of IPV etiology and intervention using motivational interviewing.

PMID- 22593610
TI  - Applications of Preference Assessment Procedures in Depression and Agitation
      Management in Elders with Dementia.
AB  - Low levels of engagement with leisure activities are commonly seen in older
      adults with dementia and may lead to decreased social contact, depressed affect,
      and agitated behaviors. Adults with dementia often have difficulty choosing
      activities when asked directly about preferences due to cognitive decline, which
      makes it more difficult to increase their engagement levels. However, simply
      presenting leisure items without prior knowledge of preferences may be
      inefficient and may not yield desired results. Long-term care staff need more
      structured and efficient ways to determine individual preferences and preference
      assessments (structured choice making opportunities) may offer a solution.
      Preference assessments have been used to identify effective reinforcers for both
      individuals with developmental disabilities and older adults with dementia and
      can provide staff with a brief method for identifying enjoyable activities. This
      study examined the utility of using stimuli (identified from preference
      assessments) in behavioral management protocols with 11 elders (mean age = 85.6
      years) with dementia in a long-term care setting. Behavioral outcomes of
      depression and agitation were evaluated at baseline and throughout the
      intervention. Results indicated positive improvement in behavioral symptoms in 8
      of 11 participants. The utility of using preferred items in behavioral management
      protocols was supported for reducing agitated behaviors but was only partially
      supported for decreasing depressive symptoms in individuals with dementia.

PMID- 22593612
TI  - Humoral and cellular capsid-specific immune responses to adeno-associated virus
      type 1 in randomized healthy donors.
AB  - A major impediment to the use of adeno-associated virus (AAV)-mediated gene
      delivery to muscle in clinical applications is the pre-existing immune responses
      against the vector. Pre-existing humoral response to different AAV serotypes is
      now well documented. In contrast, cellular responses to AAV capsid have not been
      analyzed in a systematic manner, despite the risk of T cell reactivation upon
      gene transfer. AAV1 has been widely used in humans to target muscle. In this
      study, we analyzed PBMCs and sera of healthy donors for the presence of AAV1
      capsid-specific T cell responses and AAV1 neutralizing factors. Approximately 30%
      of donors presented AAV1 capsid-specific T cells, mainly effector memory CD8(+)
      cells. IFN-gamma-producing cells were also observed among effector memory CD4(+)
      cells for two of these donors. Moreover, to our knowledge, this study shows for
      the first time on a large cohort that there was no correlation between AAV1
      specific T cell and humoral responses. Indeed, most donors presenting specific Ig
      and neutralizing factors were negative for cellular response (and vice versa).
      These new data raise the question of prescreening patients not only for the
      humoral response, but also for the cellular response. Clearly, a better
      understanding of the natural immunology of AAV serotypes will allow us to improve
      AAV gene therapy and make it an efficient treatment for genetic disease.

PMID- 22593611
TI  - Stromal endothelial cells establish a bidirectional crosstalk with chronic
      lymphocytic leukemia cells through the TNF-related factors BAFF, APRIL, and
      CD40L.
AB  - Chronic lymphocytic leukemia (CLL) is a clonal B cell disorder of unknown origin.
      Accessory signals from the microenvironment are critical for the survival,
      expansion, and progression of malignant B cells. We found that the CLL stroma
      included microvascular endothelial cells (MVECs) expressing BAFF and APRIL, two
      TNF family members related to the T cell-associated B cell-stimulating molecule
      CD40L. Constitutive release of soluble BAFF and APRIL increased upon engagement
      of CD40 on MVECs by CD40L aberrantly expressed on CLL cells. In addition to
      enhancing MVEC expression of CD40, leukemic CD40L induced cleavases that elicited
      intracellular processing of pro-BAFF and pro-APRIL proteins in MVECs. The
      resulting soluble BAFF and APRIL proteins delivered survival, activation, Ig gene
      remodeling, and differentiation signals by stimulating CLL cells through TACI,
      BAFF-R, and BCMA receptors. BAFF and APRIL further amplified CLL cell survival by
      upregulating the expression of leukemic CD40L. Inhibition of TACI, BCMA, and BAFF
      R expression on CLL cells; abrogation of CD40 expression in MVECs; or suppression
      of BAFF and APRIL cleavases in MVECs reduced the survival and diversification of
      malignant B cells. These data indicate that BAFF, APRIL, and CD40L form a CLL
      enhancing bidirectional signaling network linking neoplastic B cells with the
      microvascular stroma.

PMID- 22593613
TI  - An in vivo IL-7 requirement for peripheral Foxp3+ regulatory T cell homeostasis.
AB  - All T cells are dependent on IL-7 for their development and for homeostasis.
      Foxp3(+) regulatory T cells (Tregs) are unique among T cells in that they are
      dependent on IL-2. Whether such IL-2 dependency is distinct from or in addition
      to an IL-7 requirement has been a confounding issue, particularly because of the
      absence of an adequate experimental system to address this question. In this
      study, we present a novel in vivo mouse model where IL-2 expression is intact but
      IL-7 expression was geographically limited to the thymus. Consequently, IL-7 is
      not available in peripheral tissues. Such mice were generated by introducing a
      thymocyte-specific IL-7 transgene onto an IL-7 null background. In these mice, T
      cell development in the thymus, including Foxp3(+) Treg numbers, was completely
      restored, which correlates with the thymus-specific expression of transgenic IL
      7. In peripheral cells, however, IL-7 expression was terminated, which resulted
      in a general paucity of T cells and a dramatic reduction of Foxp3(+) Treg
      numbers. Loss of Tregs was further accompanied by a significant reduction in
      Foxp3(+) expression levels. These data suggest that peripheral IL-7 is not only
      necessary for Treg survival but also for upregulating Foxp3 expression.
      Collectively, we assessed the effect of a selective peripheral IL-7 deficiency in
      the presence of a fully functional thymus, and we document a critical requirement
      for in vivo IL-7 in T cell maintenance and specifically in Foxp3(+) cell
      homeostasis.

PMID- 22593614
TI  - Enhanced anti-serpin antibody activity inhibits autoimmune inflammation in type 1
      diabetes.
AB  - Intracellular (clade B) OVA-serpin protease inhibitors play an important role in
      tissue homeostasis by protecting cells from death in response to hypo-osmotic
      stress, heat shock, and other stimuli. It is not known whether these serpins
      influence immunological tolerance and the risk for autoimmune diseases. We found
      that a fraction of young autoimmune diabetes-prone NOD mice had elevated levels
      of autoantibodies against a member of clade B family known as serpinB13. High
      levels of anti-serpinB13 Abs were accompanied by low levels of anti-insulin
      autoantibodies, reduced numbers of islet-associated T cells, and delayed onset of
      diabetes. Exposure to anti-serpinB13 mAb alone also decreased islet inflammation,
      and coadministration of this reagent and a suboptimal dose of anti-CD3 mAb
      accelerated recovery from diabetes. In a fashion similar to that discovered in
      the NOD model, a deficiency in humoral activity against serpinB13 was associated
      with early onset of human type 1 diabetes. These findings suggest that, in
      addition to limiting exposure to proteases within the cell, clade B serpins help
      to maintain homeostasis by inducing protective humoral immunity.

PMID- 22593615
TI  - RGS16 attenuates pulmonary Th2/Th17 inflammatory responses.
AB  - The regulators of G protein signaling (RGS) protein superfamily negatively
      controls G protein-coupled receptor signal transduction pathways. RGS16 is
      enriched in activated/effector T lymphocytes. In this paper, we show that RGS16
      constrains pulmonary inflammation by regulating chemokine-induced T cell
      trafficking in response to challenge with Schistosoma mansoni. Naive Rgs16(-/-)
      mice were "primed" for inflammation by accumulation of CCR10(+) T cells in the
      lung. Upon pathogen exposure, these mice developed more robust granulomatous lung
      fibrosis than wild-type counterparts. Distinct Th2 or putative Th17 subsets
      expressing CCR4 or CCR10 accumulated more rapidly in Rgs16(-/-) lungs following
      challenge and produced proinflammatory cytokines IL-13 and IL-17B. CCR4(+)Rgs16(
      /-) Th2 cells migrated excessively to CCL17 and localized aberrantly in
      challenged lungs. T lymphocytes were partially excluded from lung granulomas in
      Rgs16(-/-) mice, instead forming peribronchial/perivascular aggregates. Thus,
      RGS16-mediated confinement of T cells to Schistosome granulomas mitigates
      widespread cytokine-mediated pulmonary inflammation.

PMID- 22593616
TI  - Passive immunoprotection of Plasmodium falciparum-infected mice designates the
      CyRPA as candidate malaria vaccine antigen.
AB  - An effective malaria vaccine could prove to be the most cost-effective and
      efficacious means of preventing severe disease and death from malaria. In an
      endeavor to identify novel vaccine targets, we tested predicted Plasmodium
      falciparum open reading frames for proteins that elicit parasite-inhibitory Abs.
      This has led to the identification of the cysteine-rich protective Ag (CyRPA).
      CyRPA is a cysteine-rich protein harboring a predicted signal sequence. The stage
      specific expression of CyRPA in late schizonts resembles that of proteins known
      to be involved in merozoite invasion. Immunofluorescence staining localized CyRPA
      at the apex of merozoites. The entire protein is conserved as shown by sequencing
      of the CyRPA encoding gene from a diverse range of P. falciparum isolates. CyRPA
      specific mAbs substantially inhibited parasite growth in vitro as well as in a P.
      falciparum animal model based on NOD-scid IL2Rgamma(null) mice engrafted with
      human erythrocytes. In contrast to other P. falciparum mouse models, this system
      generated very consistent results and evinced a dose-response relationship and
      therefore represents an unprecedented in vivo model for quantitative comparison
      of the functional potencies of malaria-specific Abs. Our data suggest a role for
      CyRPA in erythrocyte invasion by the merozoite. Inhibition of merozoite invasion
      by CyRPA-specific mAbs in vitro and in vivo renders this protein a promising
      malaria asexual blood-stage vaccine candidate Ag.

PMID- 22593617
TI  - B cell receptor-ERK1/2 signal cancels PAX5-dependent repression of BLIMP1 through
      PAX5 phosphorylation: a mechanism of antigen-triggering plasma cell
      differentiation.
AB  - Plasma cell differentiation is initiated by Ag stimulation of BCR. Until BCR
      stimulation, B lymphocyte-induced maturation protein 1 (BLIMP1), a master
      regulator of plasma cell differentiation, is suppressed by PAX5, which is a key
      transcriptional repressor for maintaining B cell identity. After BCR stimulation,
      upregulation of BLIMP1 and subsequent suppression of PAX5 by BLIMP1 are observed
      and thought to be the trigger of plasma cell differentiation; however, the
      trigger that derepresses BLIMP1 expression is yet to be revealed. In this study,
      we demonstrated PAX5 phosphorylation by ERK1/2, the main component of the BCR
      signal. Transcriptional repression on BLIMP1 promoter by PAX5 was canceled by
      PAX5 phosphorylation. BCR stimulation induced ERK1/2 activation, phosphorylation
      of endogenous PAX5, and upregulation of BLIMP1 mRNA expression in B cells. These
      phenomena were inhibited by MEK1 inhibitor or the phosphorylation-defective
      mutation of PAX5. These data imply that PAX5 phosphorylation by the BCR signal is
      the initial event in plasma cell differentiation.

PMID- 22593618
TI  - Immunological disruption of antiangiogenic signals by recruited allospecific T
      cells leads to corneal allograft rejection.
AB  - Corneal transplantation is the most common solid organ transplantation. The
      immunologically privileged nature of the cornea results in high success rates.
      However, T cell-mediated rejection is the most common cause of corneal graft
      failure. Using antiangiogenesis treatment to prevent corneal neovascularization,
      which revokes immune privilege, prevents corneal allograft rejection. Endostatin
      is an antiangiogenic factor that maintains corneal avascularity. In this study,
      we directly test the role of antiangiogenic and immunological signals in corneal
      allograft survival, specifically the potential correlation of endostatin
      production and T cell recruitment. We report that 75% of the corneal allografts
      of BALB/c mice rejected after postoperative day (POD) 20, whereas all syngeneic
      grafts survived through POD60. This correlates with endogenous endostatin, which
      increased and remained high in syngeneic grafts but decreased after POD10 in
      allografts. Immunostaining demonstrated that early recruitment of allospecific T
      cells into allografts around POD10 correlated with decreased endostatin
      production. In Rag(-/-) mice, both allogeneic and syngeneic corneal grafts
      survived; endostatin remained high throughout. However, after T cell transfer,
      the allografts eventually rejected, and endostatin decreased. Furthermore,
      exogenous endostatin treatment delayed allograft rejection and promoted survival
      secondary to angiogenesis inhibition. Our results suggest that endostatin plays
      an important role in corneal allograft survival by inhibiting neovascularization
      and that early recruitment of allospecific T cells into the grafts promotes
      destruction of endostatin-producing cells, resulting in corneal
      neovascularization, massive infiltration of effector T cells, and ultimately
      graft rejection. Therefore, combined antiangiogenesis and immune suppression will
      be more effective in maintaining corneal allograft survival.

PMID- 22593619
TI  - Augmented IL-15Ralpha expression by CD40 activation is critical in synergistic
      CD8 T cell-mediated antitumor activity of anti-CD40 antibody with IL-15 in TRAMP
      C2 tumors in mice.
AB  - IL-15 has potential as an immunotherapeutic agent for cancer treatment because it
      is a critical factor for the proliferation and activation of NK and CD8(+) T
      cells. However, monotherapy of patients with malignancy with IL-15 that has been
      initiated may not be optimal, because of the limited expression of the private
      receptor, IL-15Ralpha. We demonstrated greater CD8 T cell-mediated therapeutic
      efficacy using a combination regimen of murine IL-15 administered with an
      agonistic anti-CD40 Ab (FGK4.5) that led to increased IL-15Ralpha expression on
      dendritic cells (DCs), as well as other cell types, in a syngeneic established
      TRAMP-C2 tumor model. Seventy to one hundred percent of TRAMP-C2 tumor-bearing
      wild-type C57BL/6 mice in the combination group manifested sustained remissions,
      whereas only 0-30% in the anti-CD40-alone group and none in the murine IL-15
      alone group became tumor free (p < 0.001). However, the combination regimen
      showed less efficacy in TRAMP-C2 tumor-bearing IL-15Ralpha(-/-) mice than in wild
      type mice. The combination regimen significantly increased the numbers of TRAMP
      C2 tumor-specific SPAS-1/SNC9-H(8) tetramer(+)CD8(+) T cells, which were
      associated with the protection from tumor development on rechallenge with TRAMP
      C2 tumor cells. Using an in vitro cytolytic assay that involved NK cells primed
      by wild-type or IL-15Ralpha(-/-) bone marrow-derived DCs, we demonstrated that
      the expression of IL-15Ralpha by DCs appeared to be required for optimal IL-15
      induced NK priming and killing. These findings support the view that anti-CD40
      mediated augmented IL-15Ralpha expression was critical in IL-15-associated
      sustained remissions observed in TRAMP-C2 tumor-bearing mice receiving
      combination therapy.

PMID- 22593621
TI  - HLA-B27 homodimers and free H chains are stronger ligands for leukocyte Ig-like
      receptor B2 than classical HLA class I.
AB  - Possession of HLA-B27 (B27) strongly predisposes to the development of
      spondyloarthritis. B27 forms classical heterotrimeric complexes with beta(2)
      microglobulin (beta2m) and peptide and (beta2m free) free H chain (FHC) forms
      including B27 dimers (termed B27(2)) at the cell surface. In this study, we
      characterize the interaction of HLA-B27 with LILR, leukocyte Ig-like receptor
      (LILR)B1 and LILRB2 immune receptors biophysically, biochemically, and by FACS
      staining. LILRB1 bound to B27 heterotrimers with a K(D) of 5.3 +/- 1.5 MUM but
      did not bind B27 FHC. LILRB2 bound to B27(2) and B27 FHC and B27 heterotrimers
      with K(D)s of 2.5, 2.6, and 22 +/- 6 MUM, respectively. Domain exchange
      experiments showed that B27(2) bound to the two membrane distal Ig-like domains
      of LILRB2. In FACS staining experiments, B27 dimer protein and tetramers stained
      LILRB2 transfectants five times more strongly than B27 heterotrimers. Moreover,
      LILRB2Fc bound to dimeric and other B27 FHC forms on B27-expressing cell lines
      more strongly than other HLA-class 1 FHCs. B27-transfected cells expressing B27
      dimers and FHC inhibited IL-2 production by LILRB2-expressing reporter cells to a
      greater extent than control HLA class I transfectants. B27 heterotrimers
      complexed with the L6M variant of the GAG KK10 epitope bound with a similar
      affinity to complexes with the wild-type KK10 epitope (with K(D)s of 15.0 +/- 0.8
      and 16.0 +/- 2.0 MUM, respectively). Disulfide-dependent B27 H chain dimers and
      multimers are stronger ligands for LILRB2 than HLA class I heterotrimers and H
      chains. The stronger interaction of B27 dimers and FHC forms with LILRB2 compared
      with other HLA class I could play a role in spondyloarthritis pathogenesis.

PMID- 22593620
TI  - CD23+ CD21(high) CD1d(high) B cells in inflamed lymph nodes are a locally
      differentiated population with increased antigen capture and activation
      potential.
AB  - CD23(+)CD21(high)CD1d(high) B cells in inflamed nodes (Bin cells) accumulate in
      the lymph nodes (LNs) draining inflamed joints of the TNF-alpha-transgenic mouse
      model of rheumatoid arthritis and are primarily involved in the significant
      histological and functional LN alterations that accompany disease exacerbation in
      this strain. In this study, we investigate the origin and function of Bin cells.
      We show that adoptively transferred GFP(+) sorted mature follicular B (FoB) cells
      home preferentially to inflamed LNs of TNF-alpha-transgenic mice where they
      rapidly differentiate into Bin cells, with a close correlation with the
      endogenous Bin fraction. Bin cells are also induced in wild-type LNs after
      immunization with T-dependent Ags and display a germinal center phenotype at
      higher rates compared with FoB cells. Furthermore, we show that Bin cells can
      capture and process Ag-immune complexes in a CD21-dependent manner more
      efficiently than can FoB cells, and they express greater levels of MHC class II
      and costimulatory Ags CD80 and CD86. We propose that Bin cells are a previously
      unrecognized inflammation-induced B cell population with increased Ag capture and
      activation potential, which may facilitate normal immune responses but may
      contribute to autoimmunity when chronic inflammation causes their accumulation
      and persistence in affected LNs.

PMID- 22593623
TI  - Validity of the Modified Child Psychopathy Scale for Juvenile Justice Center
      Residents.
AB  - Adult psychopathy has proven to be an important clinical and forensic construct,
      but much less is known about juvenile psychopathy. In the present study, we
      examined the construct validity of the self report modified Child Psychopathy
      Scale mCPS; Lynam (Psychological Bulletin 120:(2), 209-234, 1997) in a sample of
      57 adolescents residing in a Dutch juvenile justice center, aged between 13 and
      22 years. The mCPS total score was reliably related to high externalizing
      problems, low empathy, high anger and aggression, high impulsivity, high
      (violent) delinquency, and high alcohol/drug use. Unique relations were found for
      the antisocial-impulsive (mCPS Factor 2), but not the callous-unemotional facet
      of psychopathy (mCPS Factor 1). Our findings support the validity of the mCPS in
      that it encompasses the antisocial-impulsive facet of psychopathy, but it is less
      clear whether the mCPS sufficiently captures the affective-interpersonal facet of
      psychopathy.

PMID- 22593622
TI  - Cutting edge: Slamf8 is a negative regulator of Nox2 activity in macrophages.
AB  - Slamf8 (CD353) is a cell surface receptor that is expressed upon activation of
      macrophages (MPhis) by IFN-gamma or bacteria. In this article, we report that a
      very high NADPH oxidase (Nox2) enzyme activity was found in Slamf8(-/-) MPhis in
      response to Escherichia coli or Staphylococcus aureus, as well as to PMA. The
      elevated Nox2 activity in Slamf8(-/-) MPhis was also demonstrated in E. coli or
      S. aureus phagosomes by using a pH indicator system and was further confirmed by
      a reduction in the enzyme activity after transfection of the receptor into Slamf8
      deficient primary MPhis or RAW 264.7 cells. Upon exposure to bacteria or PMA,
      protein kinase C activity in Slamf8(-/-) MPhis is increased. This results in an
      enhanced phosphorylation of p40phox, one key component of the Nox2 enzyme
      complex, which, in turn, leads to greater Nox2 activity. Taken together, the data
      show that, in response to inflammation-associated stimuli, the inducible receptor
      Slamf8 negatively regulates inflammatory responses.

PMID- 22593625
TI  - Is preview benefit from word n + 2 a common effect in reading Chinese? Evidence
      from eye movements.
AB  - Although most studies of reading English (and other alphabetic languages) have
      indicated that readers do not obtain preview benefit from word n + 2, Yang, Wang,
      Xu, and Rayner (2009) reported evidence that Chinese readers obtain preview
      benefit from word n + 2. However, this effect may not be common in Chinese
      because the character prior to the target word in Yang et al.'s experiment was
      always a very high frequency function word. In the current experiment, we
      utilized a relatively low frequency word n + 1 to examine whether an n + 2
      preview benefit effect would still exist and failed to find any preview benefit
      from word n + 2. These results are consistent with a recent study which indicated
      that foveal load modulates the perceptual span during Chinese reading (Yan,
      Kliegl, Shu, Pan, & Zhou, 2010). Implications of these results for models of eye
      movement control are discussed.

PMID- 22593624
TI  - Semantic and plausibility effects on preview benefit during eye fixations in
      Chinese reading.
AB  - The boundary paradigm (Rayner, 1975) was used to examine whether high level
      information affects preview benefit during Chinese reading. In two experiments,
      readers read sentences with a 1-character target word while their eye movements
      were monitored. In Experiment 1, the semantic relatedness between the target word
      and the preview word was manipulated so that there were semantically related and
      unrelated preview words, both of which were not plausible in the sentence
      context. No significant differences between these two preview conditions were
      found, indicating no effect of semantic preview. In Experiment 2, we further
      examined semantic preview effects with plausible preview words. There were four
      types of previews: identical, related & plausible, unrelated & plausible, and
      unrelated & implausible. The results revealed a significant effect of
      plausibility as single fixation and gaze duration on the target region were
      shorter in the two plausible conditions than in the implausible condition.
      Moreover, there was some evidence for a semantic preview benefit as single
      fixation duration on the target region was shorter in the related & plausible
      condition than the unrelated & plausible condition. Implications of these results
      for processing of high level information during Chinese reading are discussed.

PMID- 22593626
TI  - Breast reshaping in gynecomastia by the "pull-through technique": considerations
      after 15 years.
AB  - Gynecomastia corresponds to abnormal and excessive development of breast tissue
      in male patients. It may be unilateral or bilateral and, depending on breast
      volume and skin redundancy, it can be classified, according to Simon, in four
      different groups. Standard therapy is surgery and different techniques have been
      described so far, including different type of incisions in the periareolar or
      intrareolar skin. In 1996 in this journal we described our personal technique,
      called "pull-through." Our technique combines liposuction that is performed on
      two planes, subcutaneous and subglandular, and sharp parenchymal excision,
      performed through the small liposuction incisions. These incisions are short (1
      1.5 cm) and hidden in the inframammary fold and behind the anterior axillary
      pillar. Furthermore the operation can be performed under local anesthesia and
      with a short recovery period. Since then we have operated on 260 patients. We now
      present our 15 years experience and our review of literature, focused on authors
      who used and criticized our technique. Results, in terms of breast volume
      reduction, skin retraction, and minimal visibility of scars, were very good, even
      in cases more severe than in our first series (Simon's type IIb and female-to
      male transsexuals). Patients' satisfaction rate was high as well and the
      incidence of complications was low. The results we observed in our series and the
      ones presented by different authors confirmed the validity and feasibility of the
      "pull-through" technique in terms of esthetic and functional results, patient
      satisfaction, and a low incidence of complications.

PMID- 22593627
TI  - Giant lipoma of the male breast: case report and review of literature.

PMID- 22593629
TI  - Color-coded syringes for anesthesia drugs-use with care.

PMID- 22593628
TI  - Phenotypic and genotypic diversity of wine yeasts used  for acidic musts.
AB  - The aim of this study was to examine the physiological and genetic stability of
      the industrial wine yeasts Saccharomyces cerevisiae and Saccharomyces bayanus
      var. uvarum under acidic stress during fermentation. The yeasts were sub-cultured
      in aerobic or fermentative conditions in media with or without l-malic acid.
      Changes in the biochemical profiles, karyotypes, and mitochondrial DNA profiles
      were assessed after minimum 50 generations. All yeast segregates showed a
      tendency to increase the range of compounds used as sole carbon sources. The wild
      strains and their segregates were aneuploidal or diploidal. One of the four
      strains of S. cerevisiae did not reveal any changes in the electrophoretic
      profiles of chromosomal and mitochondrial DNA, irrespective of culture
      conditions. The extent of genomic changes in the other yeasts was strain
      dependent. In the karyotypes of the segregates, the loss of up to 2 and the
      appearance up to 3 bands was noted. The changes in their mtDNA patterns were much
      broader, reaching 5 missing and 10 additional bands. The only exception was S.
      bayanus var. uvarum Y.00779, characterized by significantly greater genome
      plasticity only under fermentative stress. Changes in karyotypes and mtDNA
      profiles prove that fermentative stress is the main driving force of the adaptive
      evolution of the yeasts. l-malic acid does not influence the extent of genomic
      changes and the resistance of wine yeasts exhibiting increased demalication
      activity to acidic stress is rather related to their ability to decompose this
      acid. The phenotypic changes in segregates, which were found even in yeasts that
      did not reveal deviations in their DNA profiles, show that phenotypic
      characterization may be misleading in wine yeast identification. Because of yeast
      gross genomic diversity, karyotyping even though it does not seem to be a good
      discriminative tool, can be useful in determining the stability of wine yeasts.
      Restriction analysis of mitochondrial DNA appears to be a more sensitive method
      allowing for an early detection of genotypic changes in yeasts. Thus, if both of
      these methods are applied, it is possible to conduct the quick routine assessment
      of wine yeast stability in pure culture collections depositing industrial
      strains.

PMID- 22593630
TI  - National plan for Alzheimer's disease aims to jump-start drug development:
      federal funding levels remain uncertain.

PMID- 22593631
TI  - New drugs/drug news.

PMID- 22593632
TI  - Pharmaceutical approval update.

PMID- 22593633
TI  - Belimumab (benlysta): a breakthrough therapy for systemic lupus erythematosus.

PMID- 22593634
TI  - Impact of federal and state legal trends on health care services.

PMID- 22593635
TI  - Pruritus in the elderly: clinical approaches to the improvement of quality of
      life.

PMID- 22593636
TI  - Lupus: an overview of the disease and management options.
AB  - Lupus is a chronic inflammatory autoimmune disease with a wide range of clinical
      presentations resulting from its effect on multiple organ systems. There are four
      main types of lupus: neonatal, discoid, drug-induced, and systemic lupus
      erythematosus (SLE), the type that affects the majority of patients. Patients
      with lupus experience a loss of self-tolerance as a result of abnormal
      immunological function and the production of autoantibodies, which lead to the
      formation of immune complexes that may adversely affect healthy tissue.Although
      the precise etiologic mechanism is unknown, genetic, hormonal, and environmental
      factors, as well as immune abnormalities, have been identified. Associations
      between lupus onset and age, sex, geography, and race have also been established.
      Management of this disease should be individualized and should include both
      pharmacological and nonpharmacological modalities for symptom relief and
      resolution as well as improved quality of life.

PMID- 22593637
TI  - 2012 integrative healthcare symposium: treating the pain of lyme disease and
      adopting lifestyle change as therapy.

PMID- 22593638
TI  - An alginate-layer technique for culture of Brassica oleracea L. protoplasts.
AB  - Ten accessions belonging to the Brassica oleracea subspecies alba and rubra, and
      to B. oleracea var. sabauda were used in this study. Protoplasts were isolated
      from leaves and hypocotyls of in vitro grown plants. The influence of selected
      factors on the yield, viability, and mitotic activity of protoplasts immobilized
      in calcium alginate layers was investigated. The efficiency of protoplast
      isolation from hypocotyls was lower (0.7 +/- 0.1 * 10(6) ml(-1)) than for
      protoplasts isolated from leaf mesophyll tissue (2 +/- 0.1 * 10(6) ml(-1)). High
      (70-90%) viabilities of immobilized protoplasts were recorded, independent of the
      explant sources. The highest proportion of protoplasts undergoing divisions was
      noted for cv. Reball F1, both from mesophyll (29.8 +/- 2.2%) and hypocotyl (17.5
      +/- 0.3%) tissues. Developed colonies of callus tissue were subjected to
      regeneration and as a result plants from six accessions were obtained.

PMID- 22593639
TI  - The role of the androgen receptor in the development and progression of bladder
      cancer.
AB  - Men are at a higher risk of developing bladder cancer than women. Since bladder
      cancer cell lines and tissues were found to express the androgen receptor,
      efforts have been made to inspect whether androgen-mediated androgen receptor
      signals are implicated in bladder carcinogenesis as well as cancer progression.
      Mounting evidence supports the view that bladder cancer is a member of the
      endocrine-related tumors and may clearly explain the gender-specific difference
      in the incidence. However, the underlying mechanisms of how androgen receptor
      signals regulate bladder cancer growth are still far from fully characterized.
      Moreover, it remains controversial whether the androgen receptor pathway always
      plays a dominant role in bladder cancer progression. In this review, we summarize
      the available data on the involvement of androgen receptor signaling in bladder
      cancer. In particular, current evidence demonstrating the stimulatory effects of
      androgens on tumor progression or, more convincingly, tumorigenesis via the
      androgen receptor pathway may offer great potential for androgen deprivation as a
      therapeutic or chemopreventive option in patients with bladder cancer.

PMID- 22593640
TI  - Interfacial Properties of Polyethylene Glycol/Vinyltriethoxysilane (PEG/VTES)
      Copolymers and their Application to Stain Resistance.
AB  - In this study, polyethylene glycol (PEG) and vinyltriethoxysilane (VTES) were
      used in different proportions to produce a series of PEG-VTES copolymers. The
      copolymer molecular structures were confirmed by FTIR spectroscopy. In addition,
      their surface activities were evaluated by evaluating the surface tension,
      contact angle, and foaming properties. The results showed that these surfactants
      exhibited excellent surface activities and wetting power, as well as low foaming.
      Consequently, the application of a series of PEG/VTES copolymers can make cotton
      fabrics stain resistant.

PMID- 22593642
TI  - A graphical method for assessing risk factor threshold values using the
      generalized additive model: the multi-ethnic study of atherosclerosis.
AB  - Continuous variable dichotomization is a popular technique used in the estimation
      of the effect of risk factors on health outcomes in multivariate regression
      settings. Researchers follow this practice in order to simplify data analysis,
      which it unquestionably does. However thresholds used to dichotomize those
      variables are usually ad-hoc, based on expert opinions, or mean, median or
      quantile splits and can add bias to the effect of the risk factors on specific
      outcomes and underestimate such effect. In this paper, we suggest the use of a
      semi-parametric method and visualization for improvement of the threshold
      selection in variable dichotomization while accounting for mixture distributions
      in the outcome of interest and adjusting for covariates. For clinicians, these
      empirically based thresholds of risk factors, if they exist, could be informative
      in terms of the highest or lowest point of a risk factor beyond which no
      additional impact on the outcome should be expected.

PMID- 22593643
TI  - Fluidization of nanopowders: a review.
AB  - Nanoparticles (NPs) are applied in a wide range of processes, and their use
      continues to increase. Fluidization is one of the best techniques available to
      disperse and process NPs. NPs cannot be fluidized individually; they fluidize as
      very porous agglomerates. The objective of this article is to review the
      developments in nanopowder fluidization. Often, it is needed to apply an
      assistance method, such as vibration or microjets, to obtain proper fluidization.
      These methods can greatly improve the fluidization characteristics, strongly
      increase the bed expansion, and lead to a better mixing of the bed material.
      Several approaches have been applied to model the behavior of fluidized
      nanopowders. The average size of fluidized NP agglomerates can be estimated using
      a force balance or by a modified Richardson and Zaki equation. Some first
      attempts have been made to apply computational fluid dynamics. Fluidization can
      also be used to provide individual NPs with a thin coating of another material
      and to mix two different species of nanopowder. The application of nanopowder
      fluidization in practice is still limited, but a wide range of potential
      applications is foreseen. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version
      of this article (doi:10.1007/s11051-012-0737-4) contains supplementary material,
      which is available to authorized users.

PMID- 22593644
TI  - Lymphatic filariasis and the global elimination program.

PMID- 22593641
TI  - Role of apoptosis-inducing factor, proline dehydrogenase, and NADPH oxidase in
      apoptosis and oxidative stress.
AB  - Flavoproteins catalyze a variety of reactions utilizing flavin mononucleotide or
      flavin adenine dinucleotide as cofactors. The oxidoreductase properties of
      flavoenzymes implicate them in redox homeostasis, oxidative stress, and various
      cellular processes, including programmed cell death. Here we explore three
      critical flavoproteins involved in apoptosis and redox signaling, ie, apoptosis
      inducing factor (AIF), proline dehydrogenase, and NADPH oxidase. These proteins
      have diverse biochemical functions and influence apoptotic signaling by unique
      mechanisms. The role of AIF in apoptotic signaling is two-fold, with AIF changing
      intracellular location from the inner mitochondrial membrane space to the nucleus
      upon exposure of cells to apoptotic stimuli. In the mitochondria, AIF enhances
      mitochondrial bioenergetics and complex I activity/assembly to help maintain
      proper cellular redox homeostasis. After translocating to the nucleus, AIF forms
      a chromatin degrading complex with other proteins, such as cyclophilin A. AIF
      translocation from the mitochondria to the nucleus is triggered by oxidative
      stress, implicating AIF as a mitochondrial redox sensor. Proline dehydrogenase is
      a membrane-associated flavoenzyme in the mitochondrion that catalyzes the rate
      limiting step of proline oxidation. Upregulation of proline dehydrogenase by the
      tumor suppressor, p53, leads to enhanced mitochondrial reactive oxygen species
      that induce the intrinsic apoptotic pathway. NADPH oxidases are a group of
      enzymes that generate reactive oxygen species for oxidative stress and signaling
      purposes. Upon activation, NADPH oxidase 2 generates a burst of superoxide in
      neutrophils that leads to killing of microbes during phagocytosis. NADPH oxidases
      also participate in redox signaling that involves hydrogen peroxide-mediated
      activation of different pathways regulating cell proliferation and cell death.
      Potential therapeutic strategies for each enzyme are also highlighted.

PMID- 22593645
TI  - Genetics of cleft lip and palate : a review.
AB  - Orofacial clefts, particularly non-syndromic cleft lip with or without cleft
      palate (CL/P) are the most common craniofacial deformities, affecting one in
      every 700 to 1000 newborns worldwide. Numerous efforts have been made to
      understand the etiology of CL/P so as to predict its occurrence and to prevent it
      from occurring in the future. In the recent years, advances in genetics and
      molecular biology have begun to reveal the basis of craniofacial development.
      Various genetic approaches, including genome-wide and candidate gene association
      studies as well as linkage analysis, have been undertaken to identify aetiologic
      factors, but results have often been inconclusive or contradictory. These results
      may support the presence of aetiologic heterogeneity among populations and the
      presence of multiple genes involved in the aetiology of CL/P. Despite these
      difficulties, several different genes have been implicated in harbouring genes
      that contribute to the aetiology of CL/P. In conclusion, the genetic basis of
      CL/P is still controversial because of genetic complexity of clefting.

PMID- 22593646
TI  - Metabolic enzyme considerations in cancer therapy.
AB  - The clinical application of new antineoplastic drugs has been limited because of
      low therapeutic index and lack of efficacy in humans. Thus, improvement in
      efficacy of old and new anticancer drugs has been attempted by manipulating their
      pharmacokinetic properties. Four inter-related factors, which determine the
      pharmacokinetic behavior of a drug include absorption, distribution, metabolism
      and excretion. The drug-metabolizing enzymes have been classified in two major
      groups: phase I and phase II enzymes. Phase I enzymes comprise the oxidases,
      dehydrogenases, deaminases, hydrolases. Phase II enzymes include primarily UDP
      glucuronosyltransferases (UGTs), glutathionetransferases (GSTs),
      sulfotransferases (SULTs), N-acetyl transferases (NATs), methyltransferases and
      aminoacid transferases that conjugate products of phase I reactions and parent
      compounds with appropriate functional groups to generate more water soluble
      compounds which are more readily eliminated. The importance of these enzymes in
      the metabolism of specific drugs varies according to the chemical nature of the
      drug, Drug metabolism is modulated by factors that change among species and even
      among individuals in a population. Such factors can be environmental or genetic
      in origin, and influence how a drug is metabolized and to what extent. An
      awareness of these variables is invaluable when the safety and efficacy of new
      anticancer drugs are evaluated (1).

PMID- 22593647
TI  - Appraisal of clinical profile and management of juvenile nasopharyngeal
      angiofibroma in malaysia.
AB  - Juvenile nasopharyngeal angiofibroma (JNA) is a benign but locally invasive
      tumour. Patients are usually in their adolescent age and present with epistaxis
      and nasal blockage. Diagnosis is based on clinical evaluation and the C.T. scan
      findings. Pre-operative superselective embolisation (SSE) and surgical excision
      is the treatment of choice. The out patient clinic of ORL-HNS hospital of
      University Science Malaysia received 25 referrals, all male, majority between 9
      13 years of age and few adolescents. Clinically the patients were consistent with
      symptoms of recurrent epistaxis and nasal blockage. They reported from October
      1998 to October 2001 from with in the state of Kelantan and the nearby states of
      Pahang, Kedah and Terenganu. Diagnosis was mostly made on typical radiological
      findings and the tumours were classified accordingly into four stages. SSE and
      surgical excision was carried out in all cases. Regular follow-up helped us to
      identify early recurrences which were treated with salvage surgery or
      radiotherapy in one case with extensive intracranial extension. A retrospective
      review of presenting features, diagnostic difficulties, surgical approaches and
      its outcome is presented. Maxillary swing procedure performed in three cases as a
      new surgical option in the management of JNA is also discussed.

PMID- 22593648
TI  - Effects of an indigenous contraceptive herbal formulation on gonadotrophs of the
      pituitary gland of the rat.
AB  - An indigenous contraceptive herbal formulation consisting of a mixture of
      Lepidagathis longifolia, Palaquium sp and Phyllagathis rotundifolia is being used
      by the Temuan Aborigins of Malaysia. Although the previous studies demonstrated
      that this contraceptive herbal formulation causes anovulatory estrous cycle,
      altered circulating hormone levels and fetal resorption in rats, but the effects
      of this formulation on the gonadotrphs of the pituitary gland are yet to be
      evaluated. The present study was designed to observe the morphometric changes of
      the gonadotrophs and the plasma concentrations of follicle stimulating hormone
      and leutinizing hormone. Thirty five Sprague-Dawley adult female rats were
      randomly divided into 5 groups. Experimental animals were given a combined herbal
      extract or individual herbal extract at a dose of 540 mg/kg/day subcutaneously
      for 7 days. Immunostained gonadotrophs were studied by using image analyzer. FSH
      and LH serum concentrations were determined using RIA. The FSH and LH
      concentrations were low in animals that received combined herbal extract
      (p<0.01). FSH concentration was noted to be significantly low in animals that
      received P. rotundifolia (p<0.05). The mean cell area and cell density of
      gonadotrophs of animals that received combined herbal extract were significantly
      low compared to control group (p<0.05). It was concluded that the herbal extracts
      do suppress the production of gonaotrophins along with the demonstrable
      suppresive effect on the FSH cells.

PMID- 22593649
TI  - An audit of singleton breech deliveries in a hospital with a high rate of vaginal
      delivery.
AB  - The term breech trial (TBT) has brought about radical changes but it is debatable
      whether it provides unequivocal evidence regarding the practice of breech
      deliveries. There is a need to publish the data of a study that was performed
      before the era of the TBT in a hospital where there was a high rate of breech
      vaginal delivery. The objectives were to ascertain the incidence, mode of
      delivery and fetal outcome in singleton breech deliveries. The study design was a
      retrospective cohort study where 165 consecutive breech and 165 controls
      (cephalic) were included. Statistical analysis, used were Chi squared and
      Fischer's exact test. P<0.05 is taken as the level of significance. The incidence
      of breech deliveries was found to be 3% and has remained fairly constant but the
      rate of breech vaginal delivery has fallen and the CS rates have increased. Even
      though more breech compared to controls were significantly sectioned, majority of
      the breeches {n=137 (83%)} were planned for vaginal delivery and in these
      patients two-thirds attained vaginal delivery. There was 1 fetal death in the CS
      group compared to 12 deaths in the vaginally delivered breech. However, most
      death in the breech delivered vaginally are unavoidable. In conclusion, there is
      a high rate of breech vaginal delivery in this series of patients and most
      perinatal deaths were not related to the mode of delivery.

PMID- 22593650
TI  - Development of a Purification Method of Pure Primary Lymphocytes for cell
      Viability Assays.
AB  - The maintenance of pure primary lymphocytes culture for long periods may be
      difficult because of its inability to divide continuously. In addition,
      lymphocytes separation methods such as Ficoll-Paque, RBC lysis and immunomagnetic
      microbeads separation may have some affect on cell viability. The objective of
      this study is to determine various types of lymphocytes purification methods, in
      order to prolong primary lymphocytes culture to 72 hours. The second objective is
      to use these primary lymphocytes as targets for quantitative and qualitative cell
      viability assays when analysing the action of toxins isolated from natural
      products. Human blood was drawn and purified by using Ficoll-Paque, RBC lysis or
      immunomagnetic separation column method in various combinations. The purified
      lymphocytes were also grown with and without the growth enhancement factor,
      concanavalin-A. Cell viability assays were carried out for 72 hours at 24 hours
      interval. The lymphocytes purified using RBC lysis method, with or without
      concanavalin-A can prolong 100% cell viability for 72 hours whilst lymphocytes
      purified using Ficoll-Paque and supplemented with concanavalin-A showed an
      increase in cell viability of over 250% at 72 hours incubation. It was observed
      only lymphocytes purified using Ficoll-Paque followed by the immunomagnetic
      microbeads separation method and supplemented with concanavalin-A showed overall
      cell viability increase, reaching 300% at 72 hours incubation. This method was a
      reliable model to test the cytotoxicity of the Bacillus thuringiensis parasporal
      inclusion, suggesting that the method achieves the objectives of the study.

PMID- 22593651
TI  - Meningioma: a clinicopathological evaluation.
AB  - As yet no unifying grading system for meningiomas has been adopted. We evaluate
      epidemiologic factors of meningioma in Iran & degree of agreement between the two
      commonly used grading systems namely WHO (2000) and Mahmood systems. During a 6
      year period 238 meningiomas were selected and reviewed by two independent
      pathologists using both grading systems. 205(86.1%) cases were benign, 19(8%)
      atypical and 14(5.9%) malignant. 181(18%) cases were primary and 51(27%)
      secondary; 35(68%) of the latter benign, 7(14%) atypical and 9(18%) malignant.
      All intraspinal meningiomas were benign. In benign cranial and spinal types
      female to male ratios were 1.9: 1 and 1.3: 1 ; while in atypical and malignant
      types were 1 :1.4 and 1:3.1 respectively. Mean ages were 49.9 for benign. 41.1
      for atypical and 50 for malignant types. The most frequent site of involvement in
      all grades of intracranial tumors was cerebral convexity (31.1 %). The most
      common subtype was menigothelial (65.1%). Female preponderance seen in benign
      nonrecurrent meningioma became increasingly less prominent and even reversed in
      recurrent, atypical and malignant forms. Benign recurrent tumors were similar to
      non-recurrent tumors microscopically. Kappa value comparing two grading systems
      was 0.947, so good agreements were found between Mahmood and WHO grading systems.

PMID- 22593652
TI  - The routine histopathological examination of tonsillectomy specimens at hospital
      universiti sains malaysia - a retrospective study and its implication.
AB  - Tonsillectomy is performed for several indications, the two commonest in practice
      are infective (chronic tonsillitis) and obstructive symptoms such as sleep apnea.
      The objective of this study is to determine the necessity of routinely performed
      histopathological examination of fonsillectomy specimens. In this paper, a
      retrospective evaluation of 480 specimens from 241 patient who had undergone
      tonsillectomies in Hospital Universiti Sains Malaysia between January 2004 and
      October 2005 was done. It was found that 462 (96.25 %) were reactive lymphoid
      hyperplasia and 18 (3.75 %) were follicular hyperplasia. None of them were found
      to be malignant. The result of this study indicates that routine
      histopathological examination of tonsillectomy specimens are unnecessary and
      results only in added cost and a loss of man hours.

PMID- 22593653
TI  - Prevalence of goblet cell metaplasia in endocervical and endometrial
      adenocarcinoma : a histochemical study.
AB  - To determine the prevalence of goblet cell metaplasia in endocervical and
      endometrial adenocarcinomas by histochemial staining and to investigate the most
      sensitive histochemical staining method to detect this metaplasia, a total of 90
      tissue blocks representing 30 non-neoplastic cervix, 30 non-neoplastic
      endometrium, 30 endocervical and endometrial adenocarcinoma cases were obtained
      for histochemical staining with Toluidine Blue (TB), Methylene Blue (MB),
      Mucicarmine (MUC), Periodic Acid Schiff before and after Diastase digestion (PAS,
      PAS-D), Alcian Blue pH 2.5 (AB), and Periodic Acid Schiff after Alcian Blue pH
      2.5 (PAB). The cases were blinded and evaluated by a pathologist [NHO] for the
      presence of goblet cell metaplasia, the amount of goblet cells present and the
      histochemical differentiation of the goblet cells compared with its surrounding
      glandular epithelium. Goblet cell metaplasia was present in 2 out of 30 cases in
      non-neoplastic cervix, 0 out of 30 cases in non-neoplastic endometrium, 7 out of
      15 cases in endocervical adenocarcinoma and in 2 out of 15 cases in endometrial
      adenocarcinoma. Relatively few goblet cells were seen in endometrial
      adenocarcinoma, few to moderate amounts were seen in endocervical adenocarcinoma
      and relatively more goblet cells were seen in non-neoplastic cervix. The
      differentiation of the goblet cells with its surrounding glandular epithelium was
      moderate to strong in non-neoplastic cervix and endocervical adenocarcinoma,
      while the differentiation in endometrial adenocarcinoma was weak to moderate. The
      various staining methods showed differences in presence, amount and
      differentiation of the goblet cells. Goblet cell metaplasia of the reproductive
      organs is not as rare as previously reported. There was no statistical difference
      in presence, amount and differentiation of goblet cells according to the various
      cases. The must optimum staining methods for staining goblet cells in non
      neoplastic cervix, endocervical adenocarcinoma and endometrial adenocarcinoma
      were PAS, PASD and AB.

PMID- 22593654
TI  - Arteriovenous malformation of the mandible: a rare but life-threatening disease.
AB  - AVM in the mandible is rare. It may present with recurrent episodes of
      unexplained gingival haemorrhage, bony swelling, tooth mobility or facial
      asymmetry. We reported our experience in managing a case of a 15 year old Malay
      girl who presented with a life threatening bleeding from her mandible.

PMID- 22593655
TI  - Acute renal failure and hepatitis: a rare manifestation of typhoid Fever - a case
      report.
AB  - Hepatitis complicating typhoid fever has been previously reported widely.
      Occurrence of acute renal failure and hepatitis together is exremenly rare. A
      case report of complicated acute renal failure and hepatitis in a tyhoid patient
      is reported and discussed.

PMID- 22593656
TI  - Sebaceous cell carcinoma of scalp - a rare presentation.
AB  - Sebaceous cell carcinoma of the skin is a rare malignancy of the skin appendages.
      Most commonly noticed in the orbital region. Extra orbital sebaceous cell
      carcinoma is extremely rare. The aggressive behavior of this tumor is still a
      matter of controversy. We present a case of sebaceous cell carcinoma in scalp
      region in young women.

PMID- 22593657
TI  - Acute Disseminated Encephalomyelitis (ADEM) Presenting with Bilateral Optic
      Neuritis.
AB  - A 43-year old lady presented with progressive loss of vision in both eyes
      followed by rapid deterioration of consciousness within the next few days. This
      was preceded by a viral infection one week before her presentation. At
      presentation she had evidence of meningism and signs of bilateral upper motor
      neuron lesions and was managed initially as acute meningoencephalitis with
      antibiotics. The brain CT was within normal limits but subsequent MRI of the
      brain revealed multiple foci of hyperintense lesions on T2-weighted and FLAIR
      images. The cerebrospinal fluid examination revealed lymphocytosis, and normal
      protein and glucose levels. Cultures of the CSF were negative. She was managed as
      acute disseminated encephalomyelitis (ADEM) with high-dose of intravenous
      methlyprednisolone one gram/day for three consecutive days followed by oral
      prednisolone 60 mg/day. Despite the management she lapsed into coma and succumbed
      to her illness nine days after admission.

PMID- 22593658
TI  - Ancient schwannoma of the cervical sympathetic chain : a case report.
AB  - Schwannoma of the cervical sympathetic chain is an extremely rare nerve tumour.
      We report an unusual swelling in a 41-year-old female who presented with an
      asymptomatic solitary mass in the right parapharyngeal space. Clinical
      examination and computed tomography showed displaced carotid artery in an antero
      medial direction. Surgical excision of the lesion was carried out and
      histological examination revealed an Ancient Schwannoma.

PMID- 22593659
TI  - Post-impact disaster surveillance - a medical reconnaissance team at tsunami
      struck sri lanka.
AB  - Emergency Medicine and Disaster Medicine are two specialties which are similar in
      the multidisciplinary involvement during the acute phase of the disaster.
      Recently, there was an increase in the number of disasters in the world but not
      many physicians are familiar with the principles for dealing with such
      situations, the unique organizational demands, coordination and the urgent need
      for medical assistance and relief. This case report delineates our experiences at
      a tsunami disaster area and the approach to setting up a medical relief team in
      the affected area. A medical reconnaissance team comprising of an emergency
      doctor from Hospital Universiti Sains Malaysia (H.U.S.M) and two MERCY Malaysia
      members was assembled. The team flew to Colombo on day 5 after the tsunami with
      medical supplies and related materials. The mission started from December 31(st)
      2004 until January 8(th) 2005. Our surveillance area covered the Southern and
      Eastern Province with a total distance of 1700 km along the coast. The strategies
      employed during this medical reconnaissance included risk analysis, devising a
      resources matrix, developing lines of communication and rapport with other relief
      teams, Sri Lankan government agencies, and local and international non-government
      organizations. As a result, our team was able to set up a medical relief camp and
      distribute the relief items to the tsunami victims. In conclusion, the Disaster
      Emergency Medical Assistant Team (DEMAT) from H.U.S.M and MERCY Malaysia were
      able to set up and provide medical relief with our limited resources to a large
      scale disaster situation.

PMID- 22593661
TI  - Regulation of Translation Initiation under Abiotic Stress Conditions in Plants:
      Is It a Conserved or Not so Conserved Process among Eukaryotes?
AB  - For years, the study of gene expression regulation of plants in response to
      stress conditions has been focused mainly on the analysis of transcriptional
      changes. However, the knowledge on translational regulation is very scarce in
      these organisms, despite in plants, as in the rest of the eukaryotes,
      translational regulation has been proven to play a pivotal role in the response
      to different stresses. Regulation of protein synthesis under abiotic stress was
      thought to be a conserved process, since, in general, both the translation
      factors and the translation process are basically similar in eukaryotes. However,
      this conservation is not so clear in plants as the knowledge of the mechanisms
      that control translation is very poor. Indeed, some of the basic regulators of
      translation initiation, well characterised in other systems, are still to be
      identified in plants. In this paper we will focus on both the regulation of
      different initiation factors and the mechanisms that cellular mRNAs use to bypass
      the translational repression established under abiotic stresses. For this
      purpose, we will review the knowledge from different eukaryotes but paying
      special attention to the information that has been recently published in plants.

PMID- 22593662
TI  - Esophageal foreign bodies in pediatric patients: a thirteen-year retrospective
      study.
AB  - We discuss clinical symptoms and radiological findings of variable esophageal
      foreign bodies as well as therapeutic procedures in Caucasian pediatric patients.
      A retrospective study of 192 cases of suspected esophageal foreign bodies between
      1998 and 2010 was conducted. Data were statistically analyzed by chi-square test.
      A foreign body was removed from a digestive tract of 163 children aged 6 months
      to 15 years (mean age 4.9). Most objects were located within cricopharyngeal
      sphincter. Dysphagia occurred in 43%, followed by vomiting (29%) and drooling
      (28%). The most common objects were coins. Plain chest X-rays demonstrated
      aberrations in 132 cases, and in doubtful situations an esophagram test was
      ordered. In the group of thirty-seven patients whose radiograms were normal,
      esophagoscopy revealed fifteen more objects, which were eventually successfully
      removed. No major complications occurred. Esophagram should be a second X-ray
      examination if an object is not detected in plain chest X-ray. We recommend a
      rigid esophagoscopy under general anesthesia in doubtful cases as a safe
      treatment for pediatric patients.

PMID- 22593663
TI  - Docking studies, synthesis, characterization and evaluation of their antioxidant
      and cytotoxic activities of some novel isoxazole-substituted 9-anilinoacridine
      derivatives.
AB  - A convenient synthesis of novel isoxazole-substituted 9-anilinoacridine
      derivatives 5a-j was reported. The compounds were confirmed by physical and
      analytical data and screened for in vitro antioxidant activity by DPPH method,
      reducing power assay and total antioxidant capacity method. The cytotoxic
      activity of the compounds was also studied in HEp-2 cell line. The docking
      studies of the synthesized compounds were performed towards the key nucleoside
      dsDNA by using AutoDock vina 4.0 programme. All the isoxazole-substituted
      compounds have significant activities.

PMID- 22593664
TI  - Mechanisms, risk factors, and management of acquired long QT syndrome: a
      comprehensive review.
AB  - Long QT syndrome is characterized by prolongation of the corrected QT (QTc)
      interval on the surface electrocardiogram and is associated with precipitation of
      torsade de pointes (TdP), a polymorphic ventricular tachycardia that may cause
      sudden death. Acquired long QT syndrome describes pathologic excessive
      prolongation of the QT interval, upon exposure to an environmental stressor, with
      reversion back to normal following removal of the stressor. The most common
      environmental stressor in acquired long QT syndrome is drug therapy. Acquired
      long QT syndrome is an important issue for clinicians and a significant public
      health problem concerning the large number of drugs with this adverse effect with
      a potentially fatal outcome, the large number of patients exposed to these drugs,
      and our inability to predict the risk for a given individual. In this paper, we
      focus on mechanisms underlying QT prolongation, risk factors for torsades de
      pointes and describe the short- and long-term treatment of acquired long QT
      syndrome.

PMID- 22593665
TI  - Effect of dietary supplements in reducing probability of death for uremic crises
      in dogs affected by chronic kidney disease (masked RCCT).
AB  - Chitosan and alkalinizing agents can decrease morbidity and mortality in humans
      with chronic kidney disease (CKD). Whether this holds true in dog is not known.
      Objective of the study was to determine whether a commercial dietary supplement
      containing chitosan, phosphate binders, and alkalinizing agents (Renal), compared
      to placebo, reduces mortality rate due to uremic crises in dogs with spontaneous
      CKD, fed a renal diet (RD). A masked RCCT was performed including 31 azotemic
      dogs with spontaneous CKD. Dogs enrolled in the study were randomly allocated to
      receive RD plus placebo (group A; 15 dogs) or RD plus Renal (group B; 16 dogs).
      During a first 4-week period, all dogs were fed an RD and then randomized and
      clinically evaluated up to 44 weeks. The effects of dietary supplements on
      mortality rate due to uremic crises were assessed. At 44 weeks, compared to group
      A, dogs in group B had approximately 50% lower mortality rate due to uremic
      crises (P = 0.015). Dietary supplementation with chitosan, phosphate binders, and
      alkalinizing agents, along with an RD, is beneficial in reducing mortality rate
      in dogs with spontaneous CKD.

PMID- 22593666
TI  - Optimization of ozonation process for the reduction of excess sludge production
      from activated sludge process of sago industry wastewater using central composite
      design.
AB  - Sago industries effluent containing large amounts of organic content produced
      excess sludge which is a serious problem in wastewater treatment. In this study
      ozonation has been employed for the reduction of excess sludge production in
      activated sludge process. Central composite design is used to study the effect of
      ozone treatment for the reduction of excess sludge production in sago effluent
      and to optimise the variables such as pH, ozonation time, and retention time.
      ANOVA showed that the coefficient determination value (R(2)) of VSS and COD
      reduction were 0.9689 and 0.8838, respectively. VSS reduction (81%) was achieved
      at acidic pH 6.9, 12 minutes ozonation, and retention time of 10 days. COD
      reduction (87%) was achieved at acidic pH 6.7, 8 minutes of ozonation time, and
      retention time of 6 days. Low ozonation time and high retention time influence
      maximum sludge reduction, whereas low ozonation time with low retention time was
      effective for COD reduction.

PMID- 22593667
TI  - Imaging review of skeletal tumors of the pelvis malignant tumors and tumor
      mimics.
AB  - Malignant lesions of the pelvis are not uncommon and need to be differentiated
      from benign lesions and tumor mimics. Appearances are sometimes nonspecific
      leading to consideration of a broad differential diagnosis. Clinical history,
      anatomic location, and imaging characterization can help narrow the differential
      diagnosis. The focus of this paper is to demonstrate the imaging features and the
      role of plain films, computed tomography, and magnetic resonance imaging for
      detecting and characterizing malignant osseous pelvic lesions and their common
      mimics.

PMID- 22593668
TI  - Antioxidants for preventing preeclampsia: a systematic review.
AB  - OBJECTIVE: To investigate the efficacy of antioxidants for preventing
      preeclampsia and other maternal and fetal complications among pregnant women with
      low, moderate, or high risk of preeclampsia. METHODS: We searched MEDLINE,
      Embase, CENTRAL, mRCT, and other databases, with no language or publication
      restrictions. Two independent reviewers selected randomized controlled trials
      that evaluated the use of antioxidants versus placebo and extracted the relevant
      data. Relative risks (RRs) and 95% confidence intervals (95% CIs) were
      calculated. The data were compiled through the random effects model. MAIN
      RESULTS: Fifteen studies were included (21,012 women and 21,647 fetuses). No
      statistically significant difference was found between women who received
      antioxidant treatment and women who received placebo for preeclampsia (RR = 0.92;
      95% CI: 0.82-1.04), severe preeclampsia (RR = 1.03; 95% CI: 0.87-1.22), preterm
      birth (RR = 1.03; 95% CI: 0.94-1.14), and small for gestational age <10th centile
      (RR = 0.92; 95% CI: 0.80-1.05). Side effects were numerically more frequent in
      the antioxidants group compared to placebo, but without significant statistical
      difference (RR = 1.24; 95% CI: 0.85-1.80). CONCLUSIONS: The available evidence
      reviewed does not support the use of antioxidants during pregnancy for the
      prevention of preeclampsia and other outcomes.

PMID- 22593669
TI  - Modeling focused ultrasound exposure for the optimal control of thermal dose
      distribution.
AB  - Preclinical studies indicate that focused ultrasound at exposure conditions close
      to the threshold for thermal damage can increase drug delivery at the focal
      region. Although these results are promising, the optimal control of temperature
      still remains a challenge. To address this issue, computer-simulated ultrasound
      treatments have been performed. When the treatments are delivered without taking
      into account the cooling effect exerted by the blood flow, the resulting thermal
      dose is highly variable with regions of thermal damage, regions of underdosage
      close to the vessels, and areas in between these two extremes. When the power
      deposition is adjusted so that the peak thermal dose remains close to the
      threshold for thermal damage, the thermal dose is more uniformly distributed but
      under-dosage is still visible around the thermally significant vessels. The
      results of these simulations suggest that, for focused ultrasound, as for other
      delivery methods, the only way to control temperature is to adjust the average
      energy deposition to compensate for the presence of thermally significant vessels
      in the target area. By doing this, we have shown that it is possible to reduce
      the temperature heterogeneity observed in focused ultrasound thermal treatments.

PMID- 22593670
TI  - Satisfaction with access to health services: the perspective of Estonian patients
      with rheumatoid arthritis.
AB  - In this cross-sectional study we explained the possible determinants of
      satisfaction with access to health services in patients with rheumatoid arthritis
      (RA). Of the 2000 randomly selected Estonian adult patients with RA, a total 1259
      completed the survey. Regression analysis was used to analyse the predictors of
      patients' satisfaction with access to health services. Half of the respondents
      were satisfied with their access to health services. Factors that had a negative
      impact on satisfaction included pain intensity, longer waiting times to see the
      doctors, as well as low satisfaction with the doctors. Transportation costs to
      visit a rheumatologist and higher rehabilitation expenses also affected the
      degree of satisfaction. Patients who could choose the date and time at which they
      could visit the rheumatologist or who could visit their "own" doctor were more
      likely to be satisfied than patients whose appointment times were appointed by a
      healthcare provider.

PMID- 22593671
TI  - Nitrogen-doped carbonaceous materials for removal of phenol from aqueous
      solutions.
AB  - Carbonaceous material (brown coal) modified by pyrolysis, activation, and
      enrichment in nitrogen, with two different factor reagents, have been used as
      adsorbent of phenol from liquid phase. Changes in the phenol content in the test
      solutions were monitored after subsequent intervals of adsorption with selected
      adsorbents prepared from organic materials. Significant effect of nitrogen
      present in the adsorbent material on its adsorption capacity was noted. Sorption
      capacity of these selected materials was found to depend on the time of use,
      their surface area, and pore distribution. A conformation to the most well-known
      adsorption isotherm models, Langmuir, and Freundlich ones, confirms the formation
      of mono- and heterolayer solute (phenol) coverage on the surface of the adsorbent
      applied herein. The materials proposed as adsorbents of the aqueous solution
      contaminants were proved effective, which means that the waste materials
      considered are promising activated carbon precursors for liquid phase adsorbents
      for the environmental protection.

PMID- 22593672
TI  - Plasma total cysteine and cardiovascular risk burden: action and interaction.
AB  - We hypothesized that redox analysis could provide sensitive markers of the
      oxidative pathway associated to the presence of an increasing number of
      cardiovascular risk factors (RFs), independently of type. We classified 304
      subjects without cardiovascular disease into 4 groups according to the total
      number of RFs (smoking, hypertension, hypercholesterolaemia,
      hyperhomocysteinaemia, diabetes, obesity, and their combination). Oxidative
      stress was evaluated by measuring plasma total and reduced homocysteine, cysteine
      (Cys), glutathione, cysteinylglycine, blood reduced glutathione, and
      malondialdehyde. Twenty-seven percent of subjects were in group 0 RF, 26% in 1
      RF, 31% in 2 RF, and 16% in >= 3 RF. By multivariable ordinal regression
      analysis, plasma total Cys was associated to a higher number of RF (OR = 1.068;
      95% CI = 1.027-1.110, P = 0.002). Total RF burden is associated with increased
      total Cys levels. These findings support a prooxidant effect of Cys in
      conjunction with RF burden, and shed light on the pathophysiologic role of redox
      state unbalance in preclinical atherosclerosis.

PMID- 22593673
TI  - An investigation into occasional White Spot Syndrome Virus outbreak in
      traditional paddy cum prawn fields in India.
AB  - A yearlong (September 2009-August 2010) study was undertaken to find out possible
      reasons for occasional occurrence of White Spot Syndrome Virus (WSSV) outbreak in
      the traditional prawn farms adjoining Cochin backwaters. Physicochemical and
      bacteriological parameters of water and sediment from feeder canal and four
      shrimp farms were monitored on a fortnightly basis. The physicochemical
      parameters showed variation during the two production cycles and between the
      farms studied. Dissolved oxygen (DO) content of water from feeder canal showed
      low oxygen levels (as low as 0.8 mg/L) throughout the study period. There was no
      disease outbreak in the perennial ponds. Poor water exchange coupled with
      nutrient loading from adjacent houses resulted in phytoplankton bloom in shallow
      seasonal ponds which led to hypoxic conditions in early morning and
      supersaturation of DO in the afternoon besides considerably high alkaline pH.
      Ammonia levels were found to be very high in these ponds. WSSV outbreak was
      encountered twice during the study leading to mass mortalities in the seasonal
      ponds. The hypoxia and high ammonia content in water and abrupt fluctuations in
      temperature, salinity and pH might lead to considerable stress in the shrimps
      triggering WSSV infection in these traditional ponds.

PMID- 22593675
TI  - Flavonoid-deficient mutants in grass pea (Lathyrus sativus L.): genetic control,
      linkage relationships, and mapping with aconitase and S-nitrosoglutathione
      reductase isozyme loci.
AB  - Two flavonoid-deficient mutants, designated as fldL-1 and fldL-2, were isolated
      in EMS-mutagenized (0.15%, 10 h) M(2) progeny of grass pea (Lathyrus sativus L.).
      Both the mutants contained total leaf flavonoid content only 20% of their mother
      varieties. Genetic analysis revealed monogenic recessive inheritance of the
      trait, controlled by two different nonallelic loci. The two mutants differed
      significantly in banding patterns of leaf aconitase (ACO) and S
      nitrosoglutathione reductase (GSNOR) isozymes, possessing unique bands in Aco 1,
      Aco 2, and Gsnor 2 loci. Isozyme loci inherited monogenically showing codominant
      expression in F(2) (1:2:1) and backcross (1:1) segregations. Linkage studies and
      primary trisomic analysis mapped Aco 1 and fld 1 loci on extra chromosome of
      trisomic-I and Aco 2, fld 2, and Gsnor 2 on extra chromosome of trisomic-IV in
      linked associations.

PMID- 22593674
TI  - New insights in staging and chemotherapy of African trypanosomiasis and possible
      contribution of medicinal plants.
AB  - Human African trypanosomiasis (HAT) is a fatal if untreated fly-borne
      neuroinflammatory disease caused by protozoa of the species Trypanosoma brucei
      (T.b.). The increasing trend of HAT cases has been reversed, but according to WHO
      experts, new epidemics of this disease could appear. In addition, HAT is still a
      considerable burden for life quality and economy in 36 sub-Saharan Africa
      countries with 15-20 million persons at risk. Following joined initiatives of WHO
      and private partners, the fight against HAT was re-engaged, resulting in
      considerable breakthrough. We present here what is known at this day about HAT
      etiology and pathogenesis and the new insights in the development of accurate
      tools and tests for disease staging and severity monitoring in the field. Also,
      we elaborate herein the promising progresses made in the development of less
      toxic and more efficient trypanocidal drugs including the potential of medicinal
      plants and related alternative drug therapies.

PMID- 22593676
TI  - Evaluation of the project P.A.T.H.S. based on students' weekly diaries: findings
      from eight datasets.
AB  - This paper aims to investigate the effectiveness of the Tier 1 Program of the
      Project P.A.T.H.S. (positive adolescent training through holistic social
      programmes) based on eight datasets collected between 2005 and 2009. A total of
      1,138 students who participated in the program were randomly invited (from the
      whole grade or in some classes) to write a piece of journal in the form of a
      weekly diary in order to reveal their perceptions and feelings regarding the
      program and the perceived benefits of the program. Based on an integration of
      findings from different databases, results showed that the respondents generally
      (1) had positive views on the program, (2) had positive views on the instructors,
      and (3) perceived that they had acquired competencies at the societal, school,
      familial, interpersonal, and personal levels after joining the program.
      Acknowledging the limitations of diaries, the present qualitative findings
      provide support for the effectiveness of the Tier 1 Program of the Project
      P.A.T.H.S. in Hong Kong.

PMID- 22593677
TI  - Plant regeneration and cellular behaviour studies in Celosia cristata grown in
      vivo and in vitro.
AB  - Tissue culture studies of Celosia cristata were established from various explants
      and the effects of various hormones on morphogenesis of this species were
      examined. It was found that complete plant regeneration occurred at highest
      percentage on MS medium supplemented with 2.0 mg/L NAA and 1.5 mg/L BAP, with the
      best response showed by shoot explants. In vitro flowering was observed on MS
      basal medium after six weeks. The occurrence of somaclonal variation and changes
      in cellular behavior from in vivo and in vitro grown plants were investigated
      through cytological studies and image analysis. It was observed that Mitotic
      Index (MI), mean chromosome numbers, and mean nuclear to cell area ratio of in
      vitro root meristem cells were slightly higher compared to in vivo values.
      However, in vitro plants produced lower mean cell areas but higher nuclear areas
      when compared to in vivo plants. Thus, no occurrence of somaclonal variation was
      detected, and this was supported by morphological features of the in vitro
      plants.

PMID- 22593679
TI  - Antitumor and immunopotentiating activity of polysaccharide PST001 isolated from
      the seed kernel of Tamarindus indica: an in vivo study in mice.
AB  - Antitumor activity of polysaccharide PST001 isolated from the seed kernel of
      Tamarindus indica was evaluated using different cancer cell lines. Human cancer
      cell lines A549, KB, and MCF-7 and murine cancer cell lines DLA and EAC were
      treated with PST001 and cell growth inhibition was assessed by MTT assay. In vivo
      studies were carried out for toxicity, tumor reduction and immunomodulation. The
      respective IC(50) of PST001 in A549, KB, and DLA was at 80.72, 190.99, and 91.14
      MUg/mL. Significant tumor reduction was obtained in both DLA and EAC tumors on
      treatment with PST001 which was more prominent when PST001 was administered with
      CTX/5-fluorouracil. Increase in total WBC, CD4(+) T-cell population, and bone
      marrow cellularity suggested strong immunomodulatory activity for this compound.
      No significant abnormality was observed in toxicity studies. Thus the results of
      the present study suggest that PST001 has immunomodulatory and tumor inhibitory
      activities and has the potential to be developed as an anticancer agent and
      immunomodulator either as a sole agent or as an adjuvant to other
      chemotherapeutic drugs.

PMID- 22593680
TI  - Evaluation of a positive youth development program based on the repertory grid
      test.
AB  - The repertory grid test, based on personal construct psychology, was used to
      evaluate the effectiveness of Project P.A.T.H.S. (Positive Adolescent Training
      through Holistic Social Programmes) in Hong Kong. One hundred and four program
      participants (n = 104) were randomly invited to complete a repertory grid based
      on personal construct theory in order to provide both quantitative and
      qualitative data for measuring self-identity changes after joining the program.
      Findings generally showed that the participants perceived that they understood
      themselves better and had stronger resilience after joining the program.
      Participants also saw themselves as closer to their ideal selves and other
      positive role figures (but farther away from a loser) after joining the program.
      This study provides additional support for the effectiveness of the Tier 1
      Program of Project P.A.T.H.S. in the Chinese context. This study also shows that
      the repertory grid test is a useful evaluation method to measure self-identity
      changes in participants in positive youth development programs.

PMID- 22593678
TI  - Bladder mucosal CO2 compared with gastric mucosal CO2 as a marker for low
      perfusion states in septic shock.
AB  - Recent reports indicate the possible role of bladder CO(2) as a marker of low
      perfusion states. To test this hypothesis, shock was induced in six beagle dogs
      with 1 mg/kg of E. coli lipopolysaccharide, gastric CO(2) (CO(2)-G) was measured
      with a continuous monitor, and a pulmonary catheter was inserted in the bladder
      to measure CO(2) (CO(2)-B). Levels of CO(2)-B were found to be lower than those
      of CO(2)-G, with a mean difference of 36.8 mmHg (P < 0.001), and correlation
      between both measurements was poor (r(2) = 0.16). Even when the correlation
      between CO(2)-G and DeltaCO(2)-G was narrow (r(2) = 0.86), this was not the case
      for the relationship between CO(2)-B and DeltaCO(2)-B (r(2) = 0.29). Finally, the
      correlation between CO(2)-G and base deficit was good (r(2) = 0.45), which was
      not the case with the CO(2)-B correlation (r(2) = 0.03). In our experience,
      bladder CO(2) does not correlate to hemodynamic parameters and does not
      substitute gastric CO(2) for detection of low perfusion states.

PMID- 22593681
TI  - Glucose and fat oxidation: bomb calorimeter be damned.
AB  - For both respiration and combustion, the energy loss difference between glucose
      and fat oxidation often is referenced to the efficiency of the fuel. Yet, the
      addition of anaerobic metabolism with ATP resynthesis to complete respiratory
      glucose oxidation further contributes to energy loss in the form of entropy
      changes that are not measured or quantified by calorimetry; combustion and
      respiratory fat/lactate oxidation lack this anaerobic component. Indeed, the
      presence or absence of an anaerobic energy expenditure component needs to be
      applied to the estimation of energy costs in regard to glucose, lactate, and fuel
      oxidation, especially when the measurement of oxygen uptake alone may incorrectly
      define energy expenditure.

PMID- 22593682
TI  - Isolation of a new Mexican strain of Bacillus subtilis with antifungal and
      antibacterial activities.
AB  - Although several strains of B. subtilis with antifungal activity have been
      isolated worldwide, to date there are no published reports regarding the
      isolation of a native B. subtilis strain from strawberry plants in Mexico. A
      native bacterium (Bacillus subtilis 21) demonstrated in vitro antagonistic
      activity against different plant pathogenic fungi. Under greenhouse conditions,
      it was shown that plants infected with Rhizoctonia solani and Fusarium
      verticillioides and treated with B. subtilis 21 produced augment in the number of
      leaves per plant and an increment in the length of healthy leaves in comparison
      with untreated plants. In addition, B. subtilis 21 showed activity against
      pathogenic bacteria. Secreted proteins by B. subtilis 21 were studied, detecting
      the presence of proteases and bacteriocin-like inhibitor substances that could be
      implicated in its antagonistic activity. Chitinases and zwittermicin production
      could not be detected. Then, B. subtilis 21 could potentially be used to control
      phytopathogenic fungi that infect strawberry plants.

PMID- 22593683
TI  - Effect of potent ethyl acetate fraction of Stereospermum suaveolens extract in
      streptozotocin-induced diabetic rats.
AB  - To evaluate the antihyperglycemic effect of ethyl acetate fraction of ethanol
      extract of Stereospermum suaveolens in streptozotocin-(STZ-) induced diabetic
      rats by acute and subacute models. In this paper, various fractions of ethanol
      extract of Stereospermum suaveolens were prepared and their effects on blood
      glucose levels in STZ-induced diabetic rats were studied after a single oral
      administration (200 mg/kg). Administration of the ethyl acetate fraction at 200
      mg/kg once daily for 14 days to STZ-induced diabetic rats was also carried out.
      The parameters such as the fasting blood glucose, hepatic glycogen content, and
      pancreatic antioxidant levels were monitored. In the acute study, the ethyl
      acetate fraction is the most potent in reducing the fasting serum glucose levels
      of the STZ-induced diabetic rats. The 14-day repeated oral administration of the
      ethyl acetate fraction significantly reduced the fasting blood glucose and
      pancreatic TBARS level and significantly increased the liver glycogen, pancreatic
      superoxide dismutase, and catalase activities as well as reduced glutathione
      levels. The histopathological studies during the subacute treatment have been
      shown to ameliorate the STZ-induced histological damage of pancreas. This paper
      concludes that the ethyl acetate fraction from ethanol extract of Stereospermum
      suaveolens possesses potent antihyperglycemic and antioxidant properties, thereby
      substantiating the use of plant in the indigenous system of medicine.

PMID- 22593685
TI  - Evaluation of the utility of the random amplified polymorphic DNA method and of
      the semi-specific PCR to assess the genetic diversification of the Gerbera
      jamesonii bolus line.
AB  - An attempt was made to evaluate the utility of a method which employs semi
      specific PCR using partially specific primers for the coding sequence (ET) at the
      exon-intron contact and of the RAPD method to identify eight Polish cultivars of
      gerbera. It was demonstrated that the PCR method which employs semi-specific
      primers is as simple and economical as the RAPD method, simultaneously the images
      of the multiplied by means of the semi-specific PCR method DNA fragments are more
      complex and polymorphic than those obtained through the RAPD method. The studies
      of the genetic diversification of Gerbera cultivars employing the aforementioned
      methods made it possible to conduct a concentration analysis and evaluation of
      the genetic distance between the lines, manifesting at the same time the
      superiority of the semi-random PCR method. Moreover, it transpired that the use
      of mixtures of RAPD primers not always leads to an increase of the number of
      generated polymorphic bands.

PMID- 22593684
TI  - Intracellular shuttle: the lactate aerobic metabolism.
AB  - Lactate is a highly dynamic metabolite that can be used as a fuel by several
      cells of the human body, particularly during physical exercise. Traditionally, it
      has been believed that the first step of lactate oxidation occurs in cytosol;
      however, this idea was recently challenged. A new hypothesis has been presented
      based on the fact that lactate-to-pyruvate conversion cannot occur in cytosol,
      because the LDH enzyme characteristics and cytosolic environment do not allow the
      reaction in this way. Instead, the Intracellular Lactate Shuttle hypothesis
      states that lactate first enters in mitochondria and only then is metabolized. In
      several tissues of the human body this idea is well accepted but is quite
      resistant in skeletal muscle. In this paper, we will present not only the studies
      which are protagonists in this discussion, but the potential mechanism by which
      this oxidation occurs and also a link between lactate and mitochondrial
      proliferation. This new perspective brings some implications and comes to change
      our understanding of the interaction between the energy systems, because the
      product of one serves as a substrate for the other.

PMID- 22593686
TI  - Growth, root formation, and nutrient value of triticale plants fertilized with
      biosolids.
AB  - Biosolids are utilized as nutrient rich fertilizer. Little material is available
      on benefits to forage crops resulting from fertilization with biosolids. This
      paper aimed to compare the effects of fertilization with biosolids versus
      commercial nitrogen fertilizer on growth, root formation, and nutrient value of
      triticale plants in a greenhouse experiment. Per treatment, five pots were seeded
      with five triticale seeds each. Treatments included a nonfertilized control,
      fertilization with 100, 200, 300, 400, and 500 ml biosolids per pot, and
      fertilization with a commercial nitrogen fertilizer at the recommended
      application rate and at double that rate. Biomass production, root length, root
      diameter, nitrogen, phosphorus, and potassium concentration were analyzed at
      harvest. Fertilization with biosolids increased triticale production (P < 0.001);
      production was similar for the 100 to 400 mL treatments. Root length, nitrogen,
      and phosphorus concentration increased, and potassium concentration decreased
      linearly with application rate. At the recommended rate, biomass production was
      similar between fertilization with biosolids and commercial fertilizer. However,
      plants fertilized with commercial fertilizer had considerably longer roots (P <
      0.001), higher nitrogen concentration (P < 0.05), and lower potassium
      concentration (P < 0.01) than those fertilized with biosolids. Our results
      indicate that at the recommended application rate, biomass production was similar
      between fertilization with biosolids and with commercial nitrogen fertilizer,
      indicating the value of biosolids fertilization as a potential alternative.

PMID- 22593687
TI  - The future of butyric acid in industry.
AB  - In this paper, the different applications of butyric acid and its current and
      future production status are highlighted, with a particular emphasis on the
      biofuels industry. As such, this paper discusses different issues regarding
      butyric acid fermentations and provides suggestions for future improvements and
      their approaches.

PMID- 22593688
TI  - Optimization of sunflower oil transesterification process using sodium methoxide.
AB  - In this study, the methanolysis process of sunflower oil was investigated to get
      high methyl esters (biodiesel) content using sodium methoxide. To reach to the
      best process conditions, central composite design (CCD) through response surface
      methodology (RSM) was employed. The optimal conditions predicted were the
      reaction time of 60 min, an excess stoichiometric amount of alcohol to oil ratio
      of 25%w/w and the catalyst content of 0.5%w/w, which lead to the highest methyl
      ester content (100%w/w). The methyl ester content of the mixture from gas
      chromatography analysis (GC) was compared to that of optimum point. Results,
      confirmed that there was no significant difference between the fatty acid methyl
      ester content of sunflower oil produced under the optimized condition and the
      experimental value (P >= 0.05). Furthermore, some fuel specifications of the
      resultant biodiesel were tested according to American standards for testing of
      materials (ASTM) methods. The outcome showed that the methyl ester mixture
      produced from the optimized condition met nearly most of the important biodiesel
      specifications recommended in ASTM D 6751 requirements. Thus, the sunflower oil
      methyl esters resulted from this study could be a suitable alternative for petrol
      diesels.

PMID- 22593689
TI  - Pure red cell aplasia and lymphoproliferative disorders: an infrequent
      association.
AB  - Pure red cell aplasia (PRCA) is a rare bone marrow failure syndrome defined by a
      progressive normocytic anaemia and reticulocytopenia without leukocytopenia and
      thrombocytopenia. Secondary PRCA can be associated with various haematological
      disorders, such as chronic lymphocytic leukaemia (CLL) or non-Hodgkin lymphoma
      (NHL). The aim of the present review is to investigate the infrequent association
      between PRCA and lymphoproliferative disorders. PRCA might precede the appearance
      of lymphoma, may present simultaneously with the lymphoid neoplastic disease, or
      might appear following the lymphomatic disorder. Possible pathophysiological
      molecular mechanisms to explain the rare association between PRCA and
      lymphoproliferative disorders are reported. Most cases of PRCA are presumed to be
      autoimmune mediated by antibodies against either erythroblasts or erythropoietin,
      by T-cells secreting factors selectively inhibiting erythroid colonies in the
      bone marrow or by NK cells directly lysing erythroblasts. Finally, focus is given
      to the therapeutical approach, as several treatment regimens have failed for
      PRCA. Immunosuppressive therapy and/or chemotherapy are effective for improving
      anaemia in the majority of patients with lymphoma-associated PRCA. Further
      investigation is required to define the pathophysiology of PRCA at a molecular
      level and to provide convincing evidence why it might appear as a rare
      complication of lymphoproliferative disorders.

PMID- 22593691
TI  - Griffing's methods comparison for general and specific combining ability in
      cucumber.
AB  - A comparison among two forms of half-diallel analysis was made. The different
      half-diallel techniques used were Griffing's model I, method 2 and 4. These
      methods of diallel analysis were found to be interrelated. However, as Griffing's
      model I, method 4 partitioned heterosis into different components as well as gave
      information about combining ability and this method had certainly some advantages
      over the other. The results further indicated using parental generations in the
      second Griffing method may cause biased estimate of the GCA and SCA variances.
      Thus, using the fourth Griffing method is more suitable than the other methods in
      providing time, cost, and facilities, and it is recommended as an applicable
      method.

PMID- 22593690
TI  - Assessment of control tissue for gene and protein expression studies: a
      comparison of three alternative lung sources.
AB  - The use of an appropriate control group in human research is essential in
      investigating the level of a pathological disorder. This study aimed to compare
      three alternative sources of control lung tissue and to determine their
      suitability for gene and protein expression studies. Gene and protein expression
      levels of the vascular endothelial growth factor (VEGF) and gelatinase families
      and their receptors were measured using real-time reverse transcription
      polymerase chain reaction (RT-PCR) and immunohistochemistry. The gene expression
      levels of VEGFA, placental growth factor (PGF), and their receptors, fms-related
      tyrosine kinase 1 (FLT1), and kinase insert domain receptor (KDR) as well as
      matrix metalloproteinase-2 (MMP-2) and the inhibitors, tissue inhibitor of matrix
      metalloproteinase-1 (TIMP-1) and TIMP-2 were significantly higher in lung cancer
      resections. The gene expression level of MMP-9 was significantly lower in the
      corresponding samples. Altered protein expression was also detected, depending on
      the area assessed. The results of this study show that none of the three control
      groups studied are completely suitable for gene and protein studies associated
      with the VEGF and gelatinase families, highlighting the need for researchers to
      be selective in which controls they opt for.

PMID- 22593692
TI  - A comparison of the physicochemical properties and fatty acid composition of
      indaia (Attalea dubia) and Babassu (Orbignya phalerata) oils.
AB  - The physicochemical properties and fatty acid composition of Attalea dubia
      (Mart.)  Burret (indaia) seed oil were investigated. The oil was extracted in a
      soxhlet apparatus using petroleum ether and evaluated for iodine, acid, peroxide,
      ester, and saponification values. The oil was also analyzed using infrared and
      nuclear magnetic resonance spectroscopy. The fatty acid profile of the oil was
      determined by GC-MS. For each analysis indaia oil was compared to Orbignya
      phalerata (babassu) oil. The two oils appeared to be very similar in their fatty
      acid composition, in which lauric acid (the most abundant), myristic acid,
      caprylic acid, and capric acid were the four main fatty acids detected. The
      unsaturated fatty acids content was lower for indaia oil (5.8%) than for babassu
      oil (9.4%). The results suggest that indaia palm tree could be cultivated as a
      new source of vegetable oil with potential for food and cosmetic industries.

PMID- 22593693
TI  - Highlights of thirty-year experience of CO2 laser use at the Florence (Italy)
      department of dermatology.
AB  - The CO(2) laser has been used extensively in dermatological surgery over the past
      30 years and is now recognised as the gold standard for soft tissue vaporization.
      Considering that the continuous wave CO(2) laser delivery system and the newer
      "superpulsed" and scanned CO(2) systems have progressively changed our practice
      and patient satisfaction, a long range documentation can be useful. Our
      experience has demonstrated that the use of CO(2) laser involves a reduced
      healing time, an infrequent need for anaesthesia, reduced thermal damage, less
      bleeding, less inflammation, the possibility of intra-operative histologic and/or
      cytologic examination, and easy access to anatomically difficult areas. Immediate
      side effects have been pain, erythema, edema, typically see with older methods,
      using higher power. The percentage of after-treatment keloids and hypertrophic
      scars observed was very low (~1%) especially upon the usage of lower parameters.
      The recurrence of viral lesions (condylomas and warts) have been not more
      frequent than those due to other techniques. Tumor recurrence is minor compared
      with radiotherapy or surgery. This method is a valid alternative to surgery
      and/or diathermocoagulation for microsurgery of soft tissues. Our results are at
      times not consistent with those published in the literature, stressing the
      concept that multicentric studies that harmonization methodology and the patient
      selection are vital.

PMID- 22593694
TI  - Phenolic compounds analysis of root, stalk, and leaves of nettle.
AB  - Types of nettles (Urtica dioica) were collected from different regions to analyze
      phenolic compounds in this research. Nettles are specially grown in the coastal
      part. According to this kind of properties, nettle samples were collected from
      coastal part of (Mediterranean, Aegean, Black sea, and Marmara) Turkey. Phenolic
      profile, total phenol compounds, and antioxidant activities of nettle samples
      were analyzed. Nettles were separated to the part of root, stalk, and leaves.
      Then, these parts of nettle were analyzed to understand the difference of
      phenolic compounds and amount of them. Nettle (root, stalk and leaves) samples
      were analyzed by using High-Performance Liquid Chromatography with Diode-Array
      Detection (HPLC-DAD) to qualitative and quantitative determination of the
      phenolic compounds. Total phenolic components were measured by using Folin
      Ciocalteu method. The antioxidant activity was measured by using DPPH (2,2
      diphenyl-1-picrylhydrazyl) which is generally used for herbal samples and based
      on single electron transfer (SET).

PMID- 22593695
TI  - Optimization of acid protease production by Aspergillus niger I1 on shrimp
      peptone using statistical experimental design.
AB  - Medium composition and culture conditions for the acid protease production by
      Aspergillus niger I1 were optimized by response surface methodology (RSM). A
      significant influence of temperature, KH(2)PO(4), and initial pH on the protease
      production was evaluated by Plackett-Burman design (PBD). These factors were
      further optimized using Box-Behnken design and RSM. Under the proposed optimized
      conditions, the experimental protease production (183.13 U mL(-1)) closely
      matched the yield predicted by the statistical model (172.57 U mL(-1)) with R(2)
      = 0.914. Compared with the initial M1 medium on which protease production was
      43.13 U mL(-1), a successful and significant improvement by 4.25 folds was
      achieved in the optimized medium containing (g/L): hulled grain of wheat (HGW)
      5.0; KH(2)PO(4) 1.0; NaCl 0.3; MgSO(4)(7H(2)O) 0.5; CaCl(2) (7H(2)O) 0.4; ZnSO(4)
      0.1; Na(2)HPO(4) 1.6; shrimp peptone (SP) 1.0. The pH was adjusted at 5 and the
      temperature at 30 degrees C. More interestingly, the optimization was
      accomplished using two cheap and local fermentation substrates, HGW and SP, which
      may result in a significant reduction in the cost of medium constituents.

PMID- 22593696
TI  - Automatic PET-CT image registration method based on mutual information and
      genetic algorithms.
AB  - Hybrid PET/CT scanners can simultaneously visualize coronary artery disease as
      revealed by computed tomography (CT) and myocardial perfusion as measured by
      positron emission tomography (PET). Manual registration is usually required in
      clinical practice to compensate spatial mismatch between datasets. In this paper,
      we present a registration algorithm that is able to automatically align PET/CT
      cardiac images. The algorithm bases on mutual information (MI) as registration
      metric and on genetic algorithm as optimization method. A multiresolution
      approach was used to optimize the processing time. The algorithm was tested on
      computerized models of volumetric PET/CT cardiac data and on real PET/CT
      datasets. The proposed automatic registration algorithm smoothes the pattern of
      the MI and allows it to reach the global maximum of the similarity function. The
      implemented method also allows the definition of the correct spatial
      transformation that matches both synthetic and real PET and CT volumetric
      datasets.

PMID- 22593697
TI  - Effects of linear-polarized near-infrared light irradiation on chronic pain.
AB  - In order to study the efficacy of linear-polarized near-infrared light
      irradiation (LPNIR) on relieving chronic pain in conjunction with nerve block
      (NB) or local block (LB), a 3-week prospective, randomized, double-blind,
      controlled study was conducted to evaluate the pre- and post-therapy pain
      intensity. Visual analogue scales (VASs) were measured in all patients before and
      6 months after therapy visiting the pain clinic during the period of August 2007
      to January 2008. A total of 52 patients with either shoulder periarthritis or
      myofascial pain syndrome or lateral epicondylitis were randomly assigned into two
      groups by drawing lots. Patients in Group I were treated with NB or LB plus
      LPNIR; Group II patients, for their part, were treated with the same procedures
      as in Group I, but not using LPNIR. In both groups, the pain intensity (VAS
      score) decreased significantly immediately after therapy as compared to therapy.
      There was a significant difference between the test and control groups
      immediately after therapy (P < 0.05), while no effect 6 months later. No side
      effects were observed. It is concluded that LPNIR is an effective and safe
      modality to treat various chronic pains, which has synergic effects with NB or
      LB.

PMID- 22593698
TI  - An innovative hyperbaric hypothermic machine perfusion protects the liver from
      experimental preservation injury.
AB  - PURPOSE: Hypothermic machine perfusion systems seem more effective than the
      current static storage to prevent cold ischemic liver injury. Thus, we test an
      innovative hyperbaric hypothermic machine perfusion (HHMP), which combines
      hyperbaric oxygenation of the preservation solution and continuous perfusion of
      the graft. METHODS: Rat livers were preserved with Celsior solution according to
      4 different modalities: normobaric static preservation; hyperbaric static
      preservation at 2 atmosphere absolute (ATA); normobaric dynamic preservation,
      with continuous perfusion; hyperbaric dynamic preservation, with continuous
      perfusion at 2 ATA. After 24 h cold preservation, we assessed different
      parameters. RESULTS: Compared to baseline, livers preserved with the current
      static storage showed severe ultrastructural damage, glycogen depletion and an
      increased oxidative stress. Normobaric perfused livers showed improved hepatocyte
      ultrastructure and ameliorated glycogen stores, but they still suffered a
      significant oxidative damage. The addition of hyperbaric oxygen produces an extra
      benefit by improving oxidative injury and by inducing endothelial NO synthase
      (eNOS) gene expression. CONCLUSIONS: Preservation by means of the present
      innovative HHMP reduced the liver injury occurring after the current static cold
      storage by lowering glycogen depletion and oxidative damage. Interestingly, only
      the use of hyperbaric oxygen was associated to a blunted oxidative stress and an
      increased eNOS gene expression.

PMID- 22593699
TI  - Effects of electrical stimulation on meat quality of lamb and goat meat.
AB  - Effect of various voltage of electrical stimulation (ES) on meat quality of lamb
      and goat was investigated by using a total of 36 animals at 3-5 years old.
      Constant 50 Hz frequency and 50, 100, and 250 V, 90 sec of ES were administered
      to 1/2 carcasses and were examined according their textural, physicochemical, and
      sensorial characteristics. ES decreased the pH values of lamb and goat meat, and
      accelerated the rigor mortis (P < 0.05). Additionally, ES enhanced the water
      activity, water-holding capacity, and drip loss of both animals. Shear force
      varied between lamb and goat meat, and tenderness was improved depending on
      voltage range used (P < 0.001). ES caused difference in instrumental colour (CIE
      L*a*b*) values of lamb and goat meat compared with the control groups (P < 0.05)
      during aging period at 4 degrees C. Sensorial characteristics were also improved
      with various levels of ES treatments. In conclusion, ES had positive effects on
      meat quality of lamb and goat, in contrast to undesirable consumer preferences.

PMID- 22593700
TI  - Genetic dissection of sympatric populations of brown planthopper, Nilaparvata
      lugens (Stal), using DALP-PCR molecular markers.
AB  - Direct amplified length polymorphism (DALP) combines the advantages of a high
      resolution fingerprint method and also characterizing the genetic polymorphisms.
      This molecular method was also found to be useful in brown planthopper,
      Nilaparvata lugens species complex for the analysis of genetic polymorphisms. A
      total of 11 populations of Nilaparvata spp. were collected from 6 locations from
      Malaysia. Two sympatric populations of brown planthopper, N. lugens, one from
      rice and the other from a weed grass (Leersia hexandra), were collected from each
      of five locations. N. bakeri was used as an out group. Three oligonucleotide
      primer pairs, DALP231/DALPR'5, DALP234/DALPR'5, and DALP235/DALPR'5 were applied
      in this study. The unweighted pair group method with arithmetic mean (UPGMA)
      dendrogram based on genetic distances for the 11 populations of Nilaparvata spp.
      revealed that populations belonging to the same species and the same host type
      clustered together irrespective of their geographical localities of capture. The
      populations of N. lugens formed into two distinct clusters, one was insects with
      high esterase activities usually captured from rice and the other was with low
      esterase activities usually captured from L. hexandra. N. bakeri, an out group,
      was the most isolated group. Analyses of principal components, molecular
      variance, and robustness also supported greatly to the findings of cluster
      analysis.

PMID- 22593701
TI  - Towards improved prognostic scores predicting survival in patients with brain
      metastases: a pilot study of serum lactate dehydrogenase levels.
AB  - Accurate prognostic information is desirable when counselling patients with brain
      metastases regarding their therapeutic options and life expectancy. Based on
      previous studies, we selected serum lactate dehydrogenase (LDH) as a promising
      factor on which we perform a pilot study investigating methodological aspects of
      biomarker studies in patients with brain metastases, before embarking on large
      scale studies that will look at a larger number of candidate markers in an
      expanded patient cohort. For this retrospective analysis, 100 patients with
      available information on LDH treated with palliative whole-brain radiotherapy
      were selected. A comprehensive evaluation of different LDH-based variables was
      performed in uni- and multivariate tests. Probably, the most intriguing finding
      was that LDH kinetics might be more important, or at least complement,
      information obtained from a single measurement immediately before radiotherapy.
      LDH and performance status outperformed several other variables that are part of
      prognostic models such as recursive partitioning analyses classes and graded
      prognostic assessment score. LDH kinetics might reflect disease behaviour in
      extracranial metastatic and primary sites without need for comprehensive imaging
      studies and is a quite inexpensive diagnostic test. Based on these encouraging
      results, confirmatory studies in a larger cohort of patients are warranted.

PMID- 22593702
TI  - Modeling rare species distribution at the edge: the case for the vulnerable
      endemic Pyrenean desman in France.
AB  - The endemic Pyrenean Desman (Galemys pyrenaicus) is an elusive, rare, and
      vulnerable species declining over its entire and narrow range (Spain, Portugal,
      France, and Andorra). The principal set of conservation measures in France is a 5
      years National Action Plan based on 25 conservation actions. Priority is given to
      update its present distribution and develop tools for predictive distribution
      models. We aim at building the first species distribution model and map for the
      northern edge of the range of the Desman and confronting the outputs of the model
      to target conservation efforts in the context of environmental change.
      Contrasting to former comparable studies, we derive a simpler model emphasizing
      the importance of factors linked to precipitation and not to the temperature. If
      temperature is one of the climate change key factors, depicted shrinkage in
      Desman distribution could be lower or null at the northern (French) edge
      suggesting thus a major role for this northern population in terms of
      conservation of the species. Finally, we question the applied issue of temporal
      and spatial transferability for such environmental favourability models when it
      is made at the edge of the distribution range.

PMID- 22593703
TI  - A new record for occurrence of Symphodus bailloni (Osteichthyes: Perciformes:
      Labridae) in the western Black Sea coast of Turkey.
AB  - The fish species Symphodus bailloni (Valenciennes, 1839) reported in the present
      study were collected between June 2010 and June 2011 from the western Black Sea
      coasts which were previously not recorded from the Black Sea coast of Turkey. A
      total of 717 specimens of S. bailloni were measured, ranging between 8.9 and 15.4
      cm TL. Morphometrics, meristics, and diagnostic characteristics of the species
      are presented.

PMID- 22593704
TI  - Bioimpedance vector pattern in Taiwanese and Polish college students detected by
      bioelectric impedance vector analysis: preliminary observations.
AB  - BACKGROUND AND OBJECTIVES: The study was conducted to evaluate soft tissue
      hydration and mass through pattern analysis of vector plots as height, normalized
      resistance, and reactance measurements by bioelectric impedance vector analysis
      in Taiwanese and Polish college students. METHODS: Whole-body measurements were
      made with ImpediMed bioimpedance analysis SFB7 BioImp v1.55 (Pinkenba Qld 4008,
      Australia) in 16 Taiwanese and Polish men and 16 Taiwanese and Polish women.
      RESULTS: Mean vectors of Taiwanese men and women groups versus the Polish men and
      women groups were characterized by almost the same normalized resistance
      component with reactance component (separate 95% confidence limits, P < 0.05)
      indicating that there were no differences of soft tissue hydration and mass.
      INTERPRETATION AND CONCLUSION: The evaluation of soft tissue hydration and mass
      through pattern analysis of vector plots as height, normalized resistance, and
      reactance measurements by bioelectric impedance vector analysis in Taiwanese and
      Polish college students did not differ between these two diverse ethnic groups.
      Further observational research investigating these properties in larger groups
      would be welcomed to elucidate and/or confirm these findings.

PMID- 22593705
TI  - Microbiological hazard identification and exposure assessment of poultry products
      sold in various localities of Hyderabad, India.
AB  - A study was carried out to identify microbiological hazards and assess their
      exposure associated with consumption of poultry based street food served in
      different localities of Hyderabad. The study indicated that chicken 65, chicken
      fried rice, chicken noodles, chicken Manchuria and chilly chicken are the most
      common recipes. A process flow diagram was developed to identify critical control
      points in the food item. After analysis of the samples at each level of
      preparation, it was observed that rice and noodles were kept at room temperature
      for about 5-6 hrs which was a critical control point. A total of 376 samples
      including chicken fried rice, chicken noodles, boiled noodles and boiled rice
      were collected from circle 1, 2, 3, 4, 5, 6, and 7 of Greater Hyderabad municipal
      corporation (GHMC) and analyzed for microbiological examination. The most
      prevalent pathogenic bacteria isolated were S. aureus (3.4 log 10 cfu/g) and B.
      cereus (3.4 log 10 cfu/g). Salmonella spp. was present in salads (3.2 log 10
      cfu/g) and hand washings of the food handler (3.5 log 10 cfu/g). Salmonella
      contamination was found in salads served along with chicken fried rice and
      chicken noodles than in the food.

PMID- 22593706
TI  - Supercritical extraction from vinification residues: fatty acids, alpha
      tocopherol, and phenolic compounds in the oil seeds from different varieties of
      grape.
AB  - Supercritical fluid extraction has been widely employed in the extraction of high
      purity substances. In this study, we used the technology to obtain oil from seeds
      from a variety of grapes, from vinification residues generated in the Southern
      region of the state of Rio Grande do Sul, Brazil. This work encompasses three
      varieties of Vitis vinifera (Moscato Giallo, Merlot, and Cabernet Sauvignon) and
      two of Vitis labrusca (Bordo e Isabel), harvested in 2005 and 2006. We obtained
      the highest oil content from Bordo (15.40%) in 2005 and from Merlot (14.66%),
      2006. The biggest concentration of palmitic, stearic, and linoleic acids was
      observed in Bordo, 2005, and in Bordo, Merlot, and Moscato Giallo, 2006. Bordo
      showed the highest concentration of oleic acid and alpha-tocopherol in both
      seasons too. For the equivalent of procyanidins, we did not notice significant
      difference among the varieties from the 2005 harvest. In 2006, both varieties
      Isabel and Cabernet Sauvignon showed a value slightly lower than the other
      varieties. The concentration of total phenolics was higher in Bordo and Cabernet
      Sauvignon. The presence of these substances is related to several important
      pharmacological properties and might be an alternative to conventional processes
      to obtain these bioactives.

PMID- 22593707
TI  - Review analysis of the association between the prevalence of activated brown
      adipose tissue and outdoor temperature.
AB  - Brown adipose tissue (BAT) is important for regulating body weight. Environmental
      temperature influences BAT activation. Activated BAT is identifiable using (18)F
      fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG
      PET/CT). (18)F-FDG PET/CT scans done between June 2005 and May 2009 in our
      institution in tropical southern Taiwan and BAT studies from PubMed (2002-2011)
      were reviewed, and the average outdoor temperatures during the study periods were
      obtained. A simple linear regression was used to analyze the association between
      the prevalence of activated BAT (P) and the average outdoor temperature (T). The
      review analysis for 9 BAT studies (n = 16, 765) showed a significant negative
      correlation (r = -0.741, P = 0.022) between the prevalence of activated BAT and
      the average outdoor temperature. The equation of the regression line is P(%) =
      6.99 - 0.20 * T ( degrees C). The prevalence of activated BAT decreased by 1% for
      each 5 degrees C increase in average outdoor temperature. In a neutral ambient
      temperature, the prevalence of activated BAT is low and especially rare in the
      tropics. There is a significant linear negative correlation between the
      prevalence of activated BAT and the average outdoor temperature.

PMID- 22593708
TI  - Changes of radial diffusivity and fractional anisotropy in the optic nerve and
      optic radiation of glaucoma patients.
AB  - Purpose of this study was to evaluate with diffusion-tensor imaging (DTI) changes
      of radial diffusivity (RD) and fractional anisotropy (FA) in the optic nerve (ON)
      and optic radiation (OR) in glaucoma and to determine whether changes in RD and
      FA correlate with disease severity. Therefore, glaucoma patients and controls
      were examined using 3T. Regions of interest were positioned on RD and FA maps,
      and mean values were calculated for ON and OR and correlated with optic nerve
      atrophy and reduced spatial-temporal contrast sensitivity (STCS) of the retina.
      We found, that RD in glaucoma patients was significantly higher in the ON (0.74
      +/- 0.21 versus 0.58 +/- 0.17.10(-3) mm(2) s(-1); P < 0.05) and OR (0.79 +/- 0.23
      versus 0.62 +/- 0.14.10(-3) mm(2) s(-1); P < 0.05) compared to controls. Aside,
      FA was significantly decreased (0.48 +/- 0.15 versus 0.66 +/- 0.12 and 0.50 +/-
      0.20 versus 0.66 +/- 0.11; P < 0.05). Hereby, correlation between changes in
      RD/FA and optic nerve atrophy/STCS was observed (r > 0.77). In conclusion, DTI at
      3 Tesla allows robust RD and FA measurements in the ON and OR. Hereby, the extent
      of RD increase and FA decrease in glaucoma correlate with established
      ophthalmological examinations.

PMID- 22593709
TI  - Endothelial cell markers in patients with pseudoexfoliation syndrome.
AB  - The aim of the study was the assessment of the von Willebrand antigen (vWF Ag), E
      selectin, and P-selectin concentration in blood plasma of patients with
      pseudoexfoliation syndrome (PEX). The group studied comprised 30 patients with
      PEX, aged from 50 to 86 years (mean 73, SD +/- 8 years). Patients with
      cardiovascular and cerebrovascular diseases, diabetes mellitus, infectious
      disease, cancer, renal or liver insufficiency, connective tissue disease, current
      smoking, and hormone, antiplatelet, hypolipidemic, antioxidant, or
      antihypertensive drug therapy were excluded from the study. Each subject
      underwent a complete ophthalmological examination. Venous blood samples from the
      cubital vein were taken into sodium citrate solution. VWF Ag, sP-selectin, and sE
      selectin concentration were determined by a commercially available enzyme-linked
      immunosorbent assay (MedSystems, Diagnostica Stago/Roche, R&D). Concentrations of
      vWF Ag, soluble E-selectin, and soluble P-selectin in blood plasma in the study
      group were compared with the levels in blood plasma in the control group. No
      significant differences were found between the groups. Our results indicate that
      there might be no correlation between PEX and such endothelial cell markers as
      vWF Ag, sP-selectin, and sE-selectin concentrations. Since the study size is
      limited, further investigations to confirm that there is no association between
      endothelial dysfunction in PEX and risk of future cardiovascular disease are
      necessary.

PMID- 22593710
TI  - Synthesis of furo[3,2-b]pyrrole-5-carboxhydrazides and their Cu, Co and Ni
      complexes.
AB  - Carboxhydrazides 3 were synthesized by reaction of substituted furo[3,2-b]pyrrole
      5-carboxhydrazides 1 with 4-oxo-4H-chromene-2-carboxaldehyde 2 in the presence of
      3-methyl-benzenesulfonic acid in ethanol. Carboxhydrazides 3 were used as ligands
      for synthesis of Cu, Co, and Ni complexes 4.

PMID- 22593711
TI  - In vitro conservation of twenty-three overexploited medicinal plants belonging to
      the Indian sub continent.
AB  - Twenty-three pharmaceutically important plants, namely, Elaeocarpus spharicus,
      Rheum emodi, Indigofera tinctoria, Picrorrhiza kurroa, Bergenia ciliata,
      Lavandula officinalis, Valeriana wallichii, Coleus forskohlii, Gentiana kurroo,
      Saussurea lappa, Stevia rebaudiana, Acorus calamus, Pyrethrum cinerariaefolium,
      Aloe vera, Bacopa monnieri, Salvia sclarea, Glycyrrhiza glabra, Swertia cordata,
      Psoralea corylifolia, Jurinea mollis, Ocimum sanctum, Paris polyphylla, and
      Papaver somniferum, which are at the verge of being endangered due to their
      overexploitation and collection from the wild, were successfully established in
      vitro. Collections were made from the different biodiversity zones of India
      including Western Himalaya, Northeast Himalaya, Gangetic plain, Western Ghats,
      Semiarid Zone, and Central Highlands. Aseptic cultures were raised at the
      morphogenic level of callus, suspension, axillary shoot, multiple shoot, and
      rooted plants. Synseeds were also produced from highly proliferating shoot
      cultures of Bacopa monnieri, Glycyrrhiza glabra, Stevia rebaudiana, Valeriana
      wallichii, Gentiana kurroo, Lavandula officinalis, and Papaver somniferum. In
      vitro flowering was observed in Papaver somniferum, Psoralea corylifolia, and
      Ocimum sanctum shoots cultures. Out of 23 plants, 18 plants were successfully
      hardened under glasshouse conditions.

PMID- 22593712
TI  - Diversity of the neglected and underutilized crop species of importance in Benin.
AB  - Many of the plant species that are cultivated for food across the world are
      neglected and underutilized. To assess their diversity in Benin and identify the
      priority species and establish their research needs, a survey was conducted in 50
      villages distributed throughout the country. The study revealed 41 neglected and
      underutilized crop species (NUCS) among which 19 were identified as of priority
      base on 10 criteria among which included their extent and degree of consumption.
      Reasons for neglect vary with the producers and the agricultural technicians.
      Market surveys revealed that NUCS are important source of household incomes and
      substantially contribute to poverty reduction. Review of the literature available
      revealed that most of the species are rich in nutrients and have some proven
      medicinal values and the promotion of their use would help in combating
      malnutrition and improving the health status of the local populations. The
      knowledge gaps and research needs are immense on most of the species identified
      as no concrete scientific data is nationally available. In terms of research,
      almost all has to be done starting from basic ethnobotanical investigation. The
      results will help the scientists and students willing to conduct research on NUCS
      in Benin to better orient their research programs.

PMID- 22593713
TI  - Deficiency in galectin-3 promotes hepatic injury in CDAA diet-induced
      nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as a
      condition in which excess fat accumulates in hepatocytes. Nonalcoholic
      steatohepatitis (NASH), a severe form of NAFLD in which inflammation and fibrosis
      in the liver are noted, may eventually progress to end-stage liver disease.
      Galectin-3, a beta-galactoside-binding animal lectin, is a multifunctional
      protein. This protein is involved in inflammatory responses and carcinogenesis.
      We investigated whether galectin-3 is involved in the development of NASH by
      comparing galectin-3 knockout (gal3(-/-)) mice and wild-type (gal3(+/+)) mice
      with choline-deficient L-amino-acid-defined (CDAA) diet-induced NAFLD/NASH.
      Hepatic injury was significantly more severe in the gal3(-/-) male mice, as
      compared to the gal3(+/+) mice. Data generated by microarray analysis of gene
      expression suggested that galectin-3 deficiency causes alterations in the
      expression of various genes associated with carcinogenesis and lipid metabolism.
      Through canonical pathway analysis, involvement of PDGF and IL-6 signaling
      pathways was suggested in galectin-3 deficiency. Significant increase of CD14,
      Fos, and Jun, those that were related to lipopolysaccharide-mediated signaling,
      was candidate to promote hepatocellular damages in galectin-3 deficiency. In
      conclusion, galectin-3 deficiency in CDAA diet promotes NAFLD features. It may be
      caused by alterations in the expression profiles of various hepatic genes
      including lipopolysaccharide-mediated inflammation.

PMID- 22593714
TI  - Predictors of effects of lifestyle intervention on diabetes mellitus type 2
      patients.
AB  - The main aim of the study was to identify predictors of the effects of lifestyle
      intervention on diabetes mellitus type 2 patients by means of multivariate
      analysis. Data from a previously published randomised clinical trial, which
      compared the effects of a rehabilitation programme including standardised
      education and physical training sessions in the municipality's health care centre
      with the same duration of individual counseling in the diabetes outpatient
      clinic, were used. Data from 143 diabetes patients were analysed. The merged
      lifestyle intervention resulted in statistically significant improvements in
      patients' systolic blood pressure, waist circumference, exercise capacity,
      glycaemic control, and some aspects of general health-related quality of life.
      The linear multivariate regression models explained 45% to 80% of the variance in
      these improvements. The baseline outcomes in accordance to the logic of the
      regression to the mean phenomenon were the only statistically significant and
      robust predictors in all regression models. These results are important from a
      clinical point of view as they highlight the more urgent need for and better
      outcomes following lifestyle intervention for those patients who have worse
      general and disease-specific health.

PMID- 22593715
TI  - Survey of persistent organochlorine contaminants (PCDD, PCDF, and PCB) in fish
      collected from the Polish Baltic fishing areas.
AB  - Concentrations and congener-specific profiles of PCDDs, PCDFs, dl-PCBs, and ndl
      PCBs were determined in five species of edible fish from the Baltic Sea (ICES 24
      27): salmon (Salmo salar), Baltic herring (Clupea harengus membras), sprat
      (Sprattus sprattus balticus), sea trout (Salmo trutta m.trutta), and cod (Gadus
      morhua callarias). Marker PCBs were the dominant compounds (0.07-60.84 ng/g
      w.w.), followed by dl-PCBs (0.64-6.07 pg WHO-TEQ/g w.w.) and PCDD/PCDFs (0.22
      5.67 pg WHO-TEQ w.w). The concentration levels of contaminants varied between
      species. Salmon possessed the highest concentrations (up to 14.11 +/- 2.36 pg WHO
      TEQ/g w.w.) and cod the lowest ones (0.84 +/- 0.14 pg WHO-TEQ/g w.w.). Congener
      profile in the fish tested had similar pattern. The largest contribution to the
      dioxin toxicity was caused successively by PCB 126, 118, 156, furans (2,3,4,7,8
      PeCDF and 2,3,7,8-TCDF), and two dioxins: 1,2,3,7,8-PeCDD and 2,3,7,8-TCDD.
      Although the dietary consumption of fish from southwest region of the Baltic Sea
      did not represent a risk for human health (because of very low consumption of
      marine fish), the excessive eating of some of them may be of significance
      importance for health of various subgroups of consumers (fishermen).

PMID- 22593716
TI  - Characterization of eDNA from the clinical strain Acinetobacter baumannii AIIMS 7
      and its role in biofilm formation.
AB  - Release of extracellular DNA (eDNA) was observed during in vitro growth of a
      clinical strain of Acinetobacter baumannii. Membrane vesicles (MV) of varying
      diameter (20-200 nm) containing DNA were found to be released by transmission
      electron microscopy (TEM) and atomic force microscopy (AFM). An assessment of the
      characteristics of the eDNA with respect to size, digestion pattern by DNase
      I/restriction enzymes, and PCR-sequencing, indicates a high similarity with
      genomic DNA. Role of eDNA in static biofilm formed on polystyrene surface was
      evaluated by biofilm augmentation assay using eDNA available in different
      preparations, for example, whole cell lysate, cell-free supernatant, MV
      suspension, and purified eDNA. Biofilm augmentation was seen up to 224.64%,
      whereas biofilm inhibition was 59.41% after DNase I treatment: confirming that
      eDNA facilitates biofilm formation in A. baumannii. This is the first paper
      elucidating the characteristics and role of eDNA in A. baumannii biofilm, which
      may provide new insights into its pathogenesis.

PMID- 22593718
TI  - Evaluation of nutritional quality of dried cashew nut testa using laboratory rat
      as a model for pigs.
AB  - Dried cashew nut testa (DCNT) was characterized with respect to proximate,
      mineral, and energy profile. The crude protein, crude fibre, and fat and ash
      contents were, in g kg(-1)DM, 190.0, 103.0, 20.1, and 20.2, respectively, with
      metabolizable energy of 7.12 MJ kg(-1) DM. In a feeding trial, isoproteic diets
      containing DCNT (O, 50, 100, and 150 g kg(-1)) were fed ad libitum to 4 groups of
      Sprague-Dawley male rats (110 g body weight, n = 20) for a period of 4 weeks. The
      rats, used as model for pigs, had free access to water. As the dietary DCNT
      content was increased from 0 to 150 g kg(-1), there was a significant (P < 0.01)
      decrease in feed intake (r = -0.99), water intake (r = -0.87), and a reduction in
      body weight gain (r = -0.93) and efficiency of feed utilization (r = 0.78).
      However, no deaths or health-related problems were recorded during the study.
      Dietary treatments had no impact on liver, heart, lungs, kidneys, and intestinal
      weights. Cost per gram feed and feed cost per gram live weight gain were reduced
      when DCNT was used. The experimental diet containing 50 g DCNT kg(-1) supported
      the best growth performance with the lowest feed cost per gram live weight gain
      of GHc0.18. Seasonal increases in the prices of conventional feedstuffs like
      maize and fishmeal would make the use of agroindustrial by-products such as DCNT
      in pig diets even more attractive.

PMID- 22593717
TI  - An alternative paradigm for the role of antimalarial plants in Africa.
AB  - Most investigations into the antimalarial activity of African plants are centered
      on finding an indigenous equivalent to artemisinin, the compound from which
      current frontline antimalarial drugs are synthesized. As a consequence, the
      standard practice in ethnopharmacological research is to use in vitro assays to
      identify compounds that inhibit parasites at nanomolar concentrations. This
      approach fails to take into consideration the high probability of acquisition of
      resistance to parasiticidal compounds since parasite populations are placed under
      direct selection for genetic that confers a survival advantage. Bearing in mind
      Africa's long exposure to malaria and extensive ethnobotanical experimentation
      with both therapies and diet, it is more likely that compounds not readily
      overcome by Plasmodium parasites would have been retained in the pharmacopeia and
      cuisine. Such compounds are characterized by acting primarily on the host rather
      than directly targeting the parasite and thus cannot be adequately explored in
      vitro. If Africa's long history with malaria has in fact produced effective plant
      therapies, their scientific elucidation will require a major emphasis on in vivo
      investigation.

PMID- 22593720
TI  - Editorial-data analysis in metabolomics.

PMID- 22593719
TI  - Novel Bradykinin Analogues Modified in the N-Terminal Part of the Molecule with a
      Variety of Acyl Substituents.
AB  - In the current work we present some pharmacological characteristics of ten new
      analogues of bradykinin (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) modified in the N
      terminal part of the molecule with a variety of acyl substituents. Of the many
      acylating agents used previously with B(2) receptor antagonists, the following
      residues were chosen: 1-adamantaneacetic acid (Aaa), 1-adamantanecarboxylic acid
      (Aca), 4-tert-butylbenzoic acid (t-Bba), 4-aminobenzoic acid (Aba), 12
      aminododecanoic acid (Adc), succinic acid (Sua), 4-hydroxybenzoic acid, 4-hydroxy
      3-methoxybenzoic acid, 3-(4-hydroxyphenyl)propionic acid and 6-hydroxy-2
      naphthoic acid. Biological activity of the compounds was assessed in the in vivo
      rat blood pressure test and the in vitro rat uterus test. Surprisingly, N
      terminal substitution of the bradykinin peptide chain itself with aforementioned
      groups resulted in antagonists of bradykinin in the pressor test and suppressed
      agonistic potency in the uterotonic test. These interesting findings need further
      studies as they can be helpful for designing more potent B(2) receptor blockers.

PMID- 22593721
TI  - Double-check: validation of diagnostic statistics for PLS-DA models in
      metabolomics studies.
AB  - Partial Least Squares-Discriminant Analysis (PLS-DA) is a PLS regression method
      with a special binary 'dummy' y-variable and it is commonly used for
      classification purposes and biomarker selection in metabolomics studies. Several
      statistical approaches are currently in use to validate outcomes of PLS-DA
      analyses e.g. double cross validation procedures or permutation testing. However,
      there is a great inconsistency in the optimization and the assessment of
      performance of PLS-DA models due to many different diagnostic statistics
      currently employed in metabolomics data analyses. In this paper, properties of
      four diagnostic statistics of PLS-DA, namely the number of misclassifications
      (NMC), the Area Under the Receiver Operating Characteristic (AUROC), Q(2) and
      Discriminant Q(2) (DQ(2)) are discussed. All four diagnostic statistics are used
      in the optimization and the performance assessment of PLS-DA models of three
      different-size metabolomics data sets obtained with two different types of
      analytical platforms and with different levels of known differences between two
      groups: control and case groups. Statistical significance of obtained PLS-DA
      models was evaluated with permutation testing. PLS-DA models obtained with NMC
      and AUROC are more powerful in detecting very small differences between groups
      than models obtained with Q(2) and Discriminant Q(2) (DQ(2)). Reproducibility of
      obtained PLS-DA models outcomes, models complexity and permutation test
      distributions are also investigated to explain this phenomenon. DQ(2) and Q(2)
      (in contrary to NMC and AUROC) prefer PLS-DA models with lower complexity and
      require higher number of permutation tests and submodels to accurately estimate
      statistical significance of the model performance. NMC and AUROC seem more
      efficient and more reliable diagnostic statistics and should be recommended in
      two group discrimination metabolomic studies. ELECTRONIC SUPPLEMENTARY MATERIAL:
      The online version of this article (doi:10.1007/s11306-011-0330-3) contains
      supplementary material, which is available to authorized users.

PMID- 22593722
TI  - Separating the wheat from the chaff: a prioritisation pipeline for the analysis
      of metabolomics datasets.
AB  - Liquid Chromatography Mass Spectrometry (LC-MS) is a powerful and widely applied
      method for the study of biological systems, biomarker discovery and
      pharmacological interventions. LC-MS measurements are, however, significantly
      complicated by several technical challenges, including: (1) ionisation
      suppression/enhancement, disturbing the correct quantification of analytes, and
      (2) the detection of large amounts of separate derivative ions, increasing the
      complexity of the spectra, but not their information content. Here we introduce
      an experimental and analytical strategy that leads to robust metabolome profiles
      in the face of these challenges. Our method is based on rigorous filtering of the
      measured signals based on a series of sample dilutions. Such data sets have the
      additional characteristic that they allow a more robust assessment of detection
      signal quality for each metabolite. Using our method, almost 80% of the recorded
      signals can be discarded as uninformative, while important information is
      retained. As a consequence, we obtain a broader understanding of the information
      content of our analyses and a better assessment of the metabolites detected in
      the analyzed data sets. We illustrate the applicability of this method using
      standard mixtures, as well as cell extracts from bacterial samples. It is evident
      that this method can be applied in many types of LC-MS analyses and more
      specifically in untargeted metabolomics.

PMID- 22593723
TI  - Individual differences in metabolomics: individualised responses and between
      metabolite relationships.
AB  - Many metabolomics studies aim to find 'biomarkers': sets of molecules that are
      consistently elevated or decreased upon experimental manipulation. Biological
      effects, however, often manifest themselves along a continuum of individual
      differences between the biological replicates in the experiment. Such differences
      are overlooked or even diminished by methods in standard use for metabolomics,
      although they may contain a wealth of information on the experiment. Properly
      understanding individual differences is crucial for generating knowledge in
      fields like personalised medicine, evolution and ecology. We propose to use
      simultaneous component analysis with individual differences constraints (SCA
      IND), a data analysis method from psychology that focuses on these differences.
      This method constructs axes along the natural biochemical differences between
      biological replicates, comparable to principal components. The model may shed
      light on changes in the individual differences between experimental groups, but
      also on whether these differences correspond to, e.g., responders and non
      responders or to distinct chemotypes. Moreover, SCA-IND reveals the individuals
      that respond most to a manipulation and are best suited for further
      experimentation. The method is illustrated by the analysis of individual
      differences in the metabolic response of cabbage plants to herbivory. The model
      reveals individual differences in the response to shoot herbivory, where two
      'response chemotypes' may be identified. In the response to root herbivory the
      model shows that individual plants differ strongly in response dynamics. Thereby
      SCA-IND provides a hitherto unavailable view on the chemical diversity of the
      induced plant response, that greatly increases understanding of the system.
      ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article
      (doi:10.1007/s11306-012-0414-8) contains supplementary material, which is
      available to authorized users.

PMID- 22593724
TI  - Pair-wise multicomparison and OPLS analyses of cold-acclimation phases in
      Siberian spruce.
AB  - Analysis of metabolomics data often goes beyond the task of discovering
      biomarkers and can be aimed at recovering other important characteristics of
      observed metabolomic changes. In this paper we explore different methods to
      detect the presence of distinctive phases in seasonal-responsive changes of
      metabolomic patterns of Siberian spruce (Picea obovata) during cold acclimation
      occurred in the period from mid-August to January. Multivariate analysis,
      specifically orthogonal projection to latent structures discriminant analysis
      (OPLS-DA), identified time points where the metabolomic patterns underwent
      substantial modifications as a whole, revealing four distinctive phases during
      acclimation. This conclusion was re-examined by a univariate analysis consisting
      of multiple pair-wise comparisons to identify homogeneity intervals for each
      metabolite. These tests complemented OPLS-DA, clarifying biological
      interpretation of the classification: about 60% of metabolites found responsive
      to the cold stress indeed changed at one or more of the time points predicted by
      OPLS-DA. However, the univariate approach did not support the proposed division
      of the acclimation period into four phases: less than 10% of metabolites altered
      during the acclimation had homogeneous levels predicted by OPLS-DA. This
      demonstrates that coupling the classification found by OPLS-DA and the analysis
      of dynamics of individual metabolites obtained by pair-wise multicomparisons
      reveals a more correct characterization of biochemical processes in freezing
      tolerant trees and leads to interpretations that cannot be deduced by either
      method alone. The combined analysis can be used in other 'omics'-studies, where
      response factors have a causal dependence (like the time in the present work) and
      pair-wise multicomparisons are not conservative. ELECTRONIC SUPPLEMENTARY
      MATERIAL: The online version of this article (doi:10.1007/s11306-011-0304-5)
      contains supplementary material, which is available to authorized users.

PMID- 22593725
TI  - Characterization of the natural variation in  Arabidopsis thaliana metabolome by
      the analysis of metabolic distance.
AB  - Metabolite fingerprinting is widely used to unravel the chemical characteristics
      of biological samples. Multivariate data analysis and other statistical tools are
      subsequently used to analyze and visualize the plasticity of the metabolome
      and/or the relationship between those samples. However, there are limitations to
      these approaches for example because of the multi-dimensionality of the data that
      makes interpretation of the data obtained from untargeted analysis almost
      impossible for an average human being. These limitations make the biological
      information that is of prime importance in untargeted studies be partially
      exploited. Even in the case of full exploitation, current methods for
      relationship elucidation focus mainly on between groups variation and
      differences. Therefore, a measure that is capable of exploiting both between- and
      within-group biological variation would be of great value. Here, we examined the
      natural variation in the metabolome of nine Arabidopsis thaliana accessions grown
      under various environmental conditions and established a measure for the
      metabolic distance between accessions and across environments. This data analysis
      approach shows that there is just a minor correlation between genetic and
      metabolic diversity of the nine accessions. On the other hand, it delivers so far
      in Arabidopsis unexplored chemical information and is shown to be biologically
      relevant for resistance studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online
      version of this article (doi:10.1007/s11306-011-0375-3) contains supplementary
      material, which is available to authorized users.

PMID- 22593726
TI  - State-of-the art data normalization methods improve NMR-based metabolomic
      analysis.
AB  - Extracting biomedical information from large metabolomic datasets by multivariate
      data analysis is of considerable complexity. Common challenges include among
      others screening for differentially produced metabolites, estimation of fold
      changes, and sample classification. Prior to these analysis steps, it is
      important to minimize contributions from unwanted biases and experimental
      variance. This is the goal of data preprocessing. In this work, different data
      normalization methods were compared systematically employing two different
      datasets generated by means of nuclear magnetic resonance (NMR) spectroscopy. To
      this end, two different types of normalization methods were used, one aiming to
      remove unwanted sample-to-sample variation while the other adjusts the variance
      of the different metabolites by variable scaling and variance stabilization
      methods. The impact of all methods tested on sample classification was evaluated
      on urinary NMR fingerprints obtained from healthy volunteers and patients
      suffering from autosomal polycystic kidney disease (ADPKD). Performance in terms
      of screening for differentially produced metabolites was investigated on a
      dataset following a Latin-square design, where varied amounts of 8 different
      metabolites were spiked into a human urine matrix while keeping the total spike
      in amount constant. In addition, specific tests were conducted to systematically
      investigate the influence of the different preprocessing methods on the structure
      of the analyzed data. In conclusion, preprocessing methods originally developed
      for DNA microarray analysis, in particular, Quantile and Cubic-Spline
      Normalization, performed best in reducing bias, accurately detecting fold
      changes, and classifying samples. ELECTRONIC SUPPLEMENTARY MATERIAL: The online
      version of this article (doi:10.1007/s11306-011-0350-z) contains supplementary
      material, which is available to authorized users.

PMID- 22593727
TI  - Esophageal granular cell tumor successfully resected by endoscopic submucosal
      dissection.
AB  - Granular cell tumors of the esophagus are rare neoplasms and their diagnosis is
      mainly based on histopathologic examination of endoscopic biopsies. With the
      development of endoscopic techniques, there has been a marked increase in local
      treatment modalities for early esophageal neoplasms. In this case report, we
      describe the removal of a granular cell tumor by the endoscopic submucosal
      dissection technique, and briefly discuss the literature on clinicopathologic
      aspects and management of granular cell tumors.

PMID- 22593728
TI  - A case of small-cell esophageal cancer with chronic renal failure undergoing
      hemodialysis safely treated with cisplatin and etoposide.
AB  - A 54-year-old male undergoing hemodialysis was admitted to our hospital because
      of difficulty in swallowing. Esophagography and esophageal endoscopy revealed an
      irregular ulcerated lesion in the cervical esophagus. It was diagnosed as a small
      cell esophageal cancer from the biopsy sample. Computed tomography showed a tumor
      infiltrating the trachea and a few lymph node metastases in the cervix, upper
      mediastinum, and abdomen. The patient was started on chemotherapy with cisplatin
      (CDDP) and etoposide (VP-16), which had been reported to be effective for small
      cell lung cancer. The patient was treated with CDDP (80 mg/m(2)) on day 1 and VP
      16 (100 mg/m(2)) on days 1, 3, and 5, every 4 weeks. On the days of chemotherapy,
      hemodialysis was started as soon as possible after completion of administration
      of the agents. No severe side effects were observed. After 4 courses of therapy,
      the patient achieved a partial response.

PMID- 22593729
TI  - Locked nailing for the treatment of displaced articular fractures of the
      calcaneus: description of a new procedure with calcanail((r)).
AB  - Although open reduction and internal fixation is considered the best method for
      treating displaced articular fractures of the calcaneus, lateral approach is at
      high risk for wound healing complications. For this reason, the authors developed
      a posterior approach and a new implant to perform both intrafocal reduction and
      internal fixation. The aim of this technical note is to describe this method of
      treatment for displaced articular fractures of the calcaneus, which offered the
      following advantages: (a) the creation of a working channel that provides also a
      significant bone autograft, (b) the intrafocal reduction of the displaced
      articular surface, (c) the insertion of a locking nail that maintains the reduced
      articular surface at the right height, (d) the possibility to switch from an ORIF
      to a reconstruction arthrodesis with the same approach and instrumentation in
      case of severely damaged posterior facet.

PMID- 22593730
TI  - Iowa gambling task: there is more to consider than long-term outcome. Using a
      linear equation model to disentangle the impact of outcome and frequency of gains
      and losses.
AB  - The Iowa Gambling Task (IGT) has been widely used to assess differences in
      decision-making under uncertainty. Recently, several studies have shown that
      healthy subjects do not meet the basic predictions of the task (i.e., prefer
      options with positive long-term outcome), hence questioning its basic
      assumptions. Since choice options are characterized by gain and net loss
      frequency in addition to long-term outcome, we hypothesized that a combination of
      features rather than a single feature would influence participants' choices.
      Offering an alternative way of modeling IGT data, we propose to use a system of
      linear equations to estimate weights that quantify the influence of each
      individual feature on decision-making in the IGT. With our proposed model it is
      possible to disentangle and quantify the impact of each of these features.
      Results from 119 healthy young subjects suggest that choice behavior is
      predominantly influenced by gain and loss frequency. Subjects preferred choices
      associated with high-frequency gains to those with low-frequency gains,
      regardless of long-term outcome. However, among options with low-frequency gains,
      subjects learned to distinguish between choices that led to advantageous and
      disadvantageous long-term consequences. This is reflected in the relationship
      between the weights for gain frequency (highest), loss frequency (intermediate),
      and long-term outcome (lowest). Further, cluster analysis of estimated feature
      weights revealed sub-groups of participants with distinct weight patterns and
      associated advantageous decision behavior. However, subjects in general do not
      learn to solely base their preference for particular decks on expected long-term
      outcome. Consequently, long-term outcome alone is not able to drive choice
      behavior on the IGT. In sum, our model facilitates a more focused conclusion
      about the factors guiding decision-making in the IGT. In addition, differences
      between clinical groups can be assessed for each factor individually.

PMID- 22593731
TI  - Sex-specific modulation of gene expression networks in murine hypothalamus.
AB  - The hypothalamus contains nuclei and cell populations that are critical in
      reproduction and that differ significantly between the sexes in structure and
      function. To examine the molecular and genetic basis for these differences, we
      quantified gene expression in the hypothalamus of 39 pairs of adult male and
      female mice belonging to the BXD strains. This experimental design enabled us to
      define hypothalamic gene coexpression networks and provided robust estimates of
      absolute expression differences. As expected, sex has the strongest effect on the
      expression of genes on the X and Y chromosomes (e.g., Uty, Xist, Kdm6a).
      Transcripts associated with the endocrine system and neuropeptide signaling also
      differ significantly. Sex-differentiated transcripts often have well delimited
      expression within specific hypothalamic nuclei that have roles in reproduction.
      For instance, the estrogen receptor (Esr1) and neurokinin B (Tac2) genes have
      intense expression in the medial preoptic and arcuate nuclei and comparatively
      high expression in females. Despite the strong effect of sex on single
      transcripts, the global pattern of covariance among transcripts is well
      preserved, and consequently, males and females have well matched coexpression
      modules. However, there are sex-specific hub genes in functionally equivalent
      modules. For example, only in males is the Y-linked gene, Uty, a highly connected
      transcript in a network that regulates chromatin modification and gene
      transcription. In females, the X chromosome paralog, Kdm6a, takes the place of
      Uty in the same network. We also find significant effect of sex on genetic
      regulation and the same network in males and females can be associated with
      markedly different regulatory loci. With the exception of a few sex-specific
      modules, our analysis reveals a system in which sets of functionally related
      transcripts are organized into stable sex-independent networks that are
      controlled at a higher level by sex-specific modulators.

PMID- 22593732
TI  - Patterning and compartment formation in the diencephalon.
AB  - The diencephalon gives rise to structures that play an important role in
      connecting the anterior forebrain with the rest of the central nervous system.
      The thalamus is the major diencephalic derivative that functions as a relay
      station between the cortex and other lower order sensory systems. Almost two
      decades ago, neuromeric/prosomeric models were proposed describing the
      subdivision and potential segmentation of the diencephalon. Unlike the laminar
      structure of the cortex, the diencephalon is progressively divided into distinct
      functional compartments consisting principally of thalamus, epithalamus,
      pretectum, and hypothalamus. Neurons generated within these domains further
      aggregate to form clusters called nuclei, which form specific structural and
      functional units. We review the recent advances in understanding the genetic
      mechanisms that are involved in the patterning and compartment formation of the
      diencephalon.

PMID- 22593733
TI  - The calcium: an early signal that initiates the formation of the nervous system
      during embryogenesis.
AB  - The calcium (Ca(2+)) signaling pathways have crucial roles in development from
      fertilization through differentiation to organogenesis. In the nervous system,
      Ca(2+) signals are important regulators for various neuronal functions, including
      formation and maturation of neuronal circuits and long-term memory. However,
      Ca(2+) signals are also involved in the earliest steps of neurogenesis including
      neural induction, differentiation of neural progenitors into neurons, and the
      neuro-glial switch. This review examines when and how Ca(2+) signals are
      generated during each of these steps with examples taken from in vivo studies in
      vertebrate embryos and from in vitro assays using embryonic and neural stem cells
      (NSCs). During the early phases of neurogenesis few investigations have been
      performed to study the downstream targets of Ca(2+) which posses EF-hand in their
      structure. This opens an entire field of research. We also discuss the highly
      specific nature of the Ca(2+) signaling pathway and its interaction with the
      other signaling pathways involved in early neural development.

PMID- 22593734
TI  - Functional significance of M-type potassium channels in nociceptive cutaneous
      sensory endings.
AB  - M-channels carry slowly activating potassium currents that regulate excitability
      in a variety of central and peripheral neurons. Functional M-channels and their
      Kv7 channel correlates are expressed throughout the somatosensory nervous system
      where they may play an important role in controlling sensory nerve activity. Here
      we show that Kv7.2 immunoreactivity is expressed in the peripheral terminals of
      nociceptive primary afferents. Electrophysiological recordings from single
      afferents in vitro showed that block of M-channels by 3 MUM XE991 sensitized
      Adelta- but not C-fibers to noxious heat stimulation and induced spontaneous,
      ongoing activity at 32 degrees C in many Adelta-fibers. These observations were
      extended in vivo: intraplantar injection of XE991 selectively enhanced the
      response of deep dorsal horn (DH) neurons to peripheral mid-range mechanical and
      higher range thermal stimuli, consistent with a selective effect on Adelta-fiber
      peripheral terminals. These results demonstrate an important physiological role
      of M-channels in controlling nociceptive Adelta-fiber responses and provide a
      rationale for the nocifensive behaviors that arise following intraplantar
      injection of the M-channel blocker XE991.

PMID- 22593735
TI  - Synaptic regulation of the hypothalamic-pituitary-adrenal axis and its modulation
      by glucocorticoids and stress.
AB  - Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been
      implicated in a range of affective and stress-related disorders. The regulatory
      systems that control HPA activity are subject to modulation by environmental
      influences, and stressful life events or circumstances can promote subsequent HPA
      dysregulation. The brain is a major regulator of the HPA axis, and stress-induced
      plasticity of the neural circuitry involved in HPA regulation might constitute an
      etiological link between stress and the development of HPA dysregulation. This
      review focuses on the synaptic regulation of neuroendocrine corticotropin
      releasing hormone (CRH) neurons of the hypothalamic paraventricular nucleus,
      which are the cells through which the brain predominantly exerts its influence on
      the HPA axis. CRH neuronal activity is largely orchestrated by three
      neurotransmitters: GABA, glutamate, and norepinephrine. We discuss our current
      understanding of the neural circuitry through which these neurotransmitters
      regulate CRH cell activity, as well as the plastic changes in this circuitry
      induced by acute and chronic stress and the resultant changes in HPA function.

PMID- 22593736
TI  - Effect of temperature on spiking patterns of neocortical layer 2/3 and layer 6
      pyramidal neurons.
AB  - The spiking patterns of neocortical pyramidal neurons are shaped by the
      conductances in their apical dendrites. We have previously shown that the spiking
      patterns of layer 5 pyramidal neurons change with temperature, probably because
      temperature modulates the electrical coupling between somatic and dendritic
      compartments. Here we determine whether temperature has similar effects on the
      spiking patterns of layer 2/3 and layer 6 pyramidal neurons in acute slices of
      mouse primary motor cortex. In both cell types, decreasing temperature led to
      more irregular spiking patterns. Our results indicate that a decrease in spiking
      regularity with decreasing temperature, probably mediated by increased electrical
      coupling between soma and dendrites, is common to all pyramidal neurons in motor
      cortex.

PMID- 22593737
TI  - The effect of moderate acute psychological stress on working memory-related
      neural activity is modulated by a genetic variation in catecholaminergic function
      in humans.
AB  - Acute stress has an important impact on higher-order cognitive functions
      supported by the prefrontal cortex (PFC) such as working memory (WM). In rodents,
      such effects are mediated by stress-induced alterations in catecholaminergic
      signaling, but human data in support of this notion is lacking. A common
      variation in the gene encoding Catechol-O-methyltransferase (COMT) is known to
      affect basal catecholaminergic availability and PFC functions. Here, we
      investigated whether this genetic variation (Val158Met) modulates effects of
      stress on WM-related neural activity in humans. In a counterbalanced crossover
      design, 41 healthy young men underwent functional magnetic resonance imaging
      (fMRI) while performing a numerical N-back WM task embedded in a stressful or
      neutral context. Moderate psychological stress was induced by a well-controlled
      procedure involving viewing strongly aversive (versus emotionally neutral) movie
      material in combination with a self-referencing instruction. Acute stress
      resulted in genotype-dependent effects on WM performance and WM-related
      activation in the dorsolateral PFC, with a relatively negative impact of stress
      in COMT Met-homozygotes as opposed to a relatively positive effect in Val
      carriers. A parallel interaction was found for WM-related deactivation in the
      anterior medial temporal lobe (MTL). Our findings suggest that individuals with
      higher baseline catecholaminergic availability (COMT Met-homozygotes) appear to
      reach a supraoptimal state under moderate levels of stress. In contrast,
      individuals with lower baselines (Val-carriers) may reach an optimal state. Thus,
      our data show that effects of acute stress on higher-order cognitive functions
      vary depending on catecholaminergic availability at baseline, and thereby
      corroborate animal models of catecholaminergic signaling that propose a non
      linear relationship between catecholaminergic activity and prefrontal functions.

PMID- 22593739
TI  - Is any awareness necessary for an Ne?
AB  - The Error-Related Negativity (Ne or ERN) is a reliable electrophysiological index
      of error processing, which has been found to be independent of whether a subject
      is aware of an error or not. A large Ne was equally seen after errors that were
      consciously detected (Aware errors) and those that were not (Unaware errors),
      compared to a small negativity for correct responses (CRN). This suggests a
      dissociation between an automatic, preconscious error processing mechanism and
      subjective evaluation. A common concern regarding this finding is that subjects
      could have been somewhat aware of their errors, but did not report them due to
      lack of confidence. Here we tested this possibility directly using a betting
      paradigm which allowed us to separate occasions in which the subjects were
      confident of their response and trials in which they were unsure. In a choice
      reaction time task, subjects directly judged the accuracy of each response
      (correct or error) and then bet on this judgment using a high, medium, or low
      amount of money. The bets were used to determine the level of confidence the
      subjects had of their response. The average across all subjects regardless of
      confidence (betting) measure replicated the reported finding of an equal Ne for
      Aware and Unaware errors which was larger than the CRN. However, when Ne
      measurement was confined to high confidence (high bet) trials in confident
      subjects, a prominent Ne was seen only for Aware errors, while confident Unaware
      errors (i.e., error trials on which subjects made high bets that they were
      correct) elicited a response that did not differ from the CRN elicited by truly
      correct answers. In contrast, for low confidence trials in unconfident subjects,
      an intermediate and equal Ne/CRN was elicited by CRN, Aware and Unaware errors.
      These results provide direct evidence that the Ne is related to error awareness,
      and suggest the amplitude of the Ne/CRN depends on individual differences in
      error reporting and confidence.

PMID- 22593738
TI  - Drawing enhances cross-modal memory plasticity in the human brain: a case study
      in a totally blind adult.
AB  - In a memory-guided drawing task under blindfolded conditions, we have recently
      used functional Magnetic Resonance Imaging (fMRI) to demonstrate that the primary
      visual cortex (V1) may operate as the visuo-spatial buffer, or "sketchpad," for
      working memory. The results implied, however, a modality-independent or amodal
      form of its operation. In the present study, to validate the role of V1 in non
      visual memory, we eliminated not only the visual input but all levels of visual
      processing by replicating the paradigm in a congenitally blind individual. Our
      novel Cognitive-Kinesthetic method was used to train this totally blind subject
      to draw complex images guided solely by tactile memory. Control tasks of tactile
      exploration and memorization of the image to be drawn, and memory-free scribbling
      were also included. FMRI was run before training and after training. Remarkably,
      V1 of this congenitally blind individual, which before training exhibited noisy,
      immature, and non-specific responses, after training produced full-fledged
      response time-courses specific to the tactile-memory drawing task. The results
      reveal the operation of a rapid training-based plasticity mechanism that recruits
      the resources of V1 in the process of learning to draw. The learning paradigm
      allowed us to investigate for the first time the evolution of plastic re
      assignment in V1 in a congenitally blind subject. These findings are consistent
      with a non-visual memory involvement of V1, and specifically imply that the
      observed cortical reorganization can be empowered by the process of learning to
      draw.

PMID- 22593740
TI  - Training-induced improvement of response selection and error detection in aging
      assessed by task switching: effects of cognitive, physical, and relaxation
      training.
AB  - Cognitive control functions decline with increasing age. The present study
      examines if different types of group-based and trainer-guided training
      effectively enhance performance of older adults in a task switching task, and how
      this expected enhancement is reflected in changes of cognitive functions, as
      measured in electrophysiological brain activity (event-related potentials). One
      hundred forty-one healthy participants aged 65 years and older were randomly
      assigned to one of four groups: physical training (combined aerobic and strength
      training), cognitive training (paper-pencil and computer-aided), relaxation and
      wellness (social control group), and a control group that did not receive any
      intervention. Training sessions took place twice a week for 90 min for a period
      of 4 months. The results showed a greater improvement of performance for
      attendants of the cognitive training group compared to the other groups. This
      improvement was evident in a reduction of mixing costs in accuracy and
      intraindividual variability of speed, indexing improved maintenance of multiple
      task sets in working memory, and an enhanced coherence of neuronal processing.
      These findings were supported by event-related brain potentials which showed
      higher amplitudes in a number of potentials associated with response selection
      (N2), allocation of cognitive resources (P3b), and error detection (Ne). Taken
      together, our findings suggest neurocognitive plasticity of aging brains which
      can be stimulated by broad and multilayered cognitive training and assessed in
      detail by electrophysiological methods.

PMID- 22593741
TI  - Simulated loss of foveal vision eliminates visual search advantage in repeated
      displays.
AB  - In the contextual cueing paradigm, incidental visual learning of repeated
      distractor configurations leads to faster search times in repeated compared to
      new displays. This contextual cueing is closely linked to the visual exploration
      of the search arrays as indicated by fewer fixations and more efficient scan
      paths in repeated search arrays. Here, we examined contextual cueing under
      impaired visual exploration induced by a simulated central scotoma that causes
      the participant to rely on extrafoveal vision. We let normal-sighted participants
      search for the target either under unimpaired viewing conditions or with a gaze
      contingent central scotoma masking the currently fixated area. Under unimpaired
      viewing conditions, participants revealed shorter search times and more efficient
      exploration of the display for repeated compared to novel search arrays and thus
      exhibited contextual cueing. When visual search was impaired by the central
      scotoma, search facilitation for repeated displays was eliminated. These results
      indicate that a loss of foveal sight, as it is commonly observed in
      maculopathies, e.g., may lead to deficits in high-level visual functions well
      beyond the immediate consequences of a scotoma.

PMID- 22593742
TI  - Object Recognition Can Be Viewpoint Dependent or Invariant - It's Just a Matter
      of Time and Task.

PMID- 22593743
TI  - Mitochondrial haplogroups define two phenotypes of osteoarthritis.
AB  - OBJECTIVE: To assess a mitochondrion-related phenotype in patients with
      osteoarthritis (OA). METHODS: Serum levels of the following OA-related
      biomarkers: matrix metalloproteinase-1 (MMP-1); MMP-3; MMP-13; myeloperoxidase
      (MPO); a peptide of the alpha-helical region of type II collagen, Coll2-1, and
      its nitrated form Coll2-1NO(2); a C-terminal neoepitope generated by the
      collagenase-mediated cleavage of collagen type II triple helix, C2C; the C
      propeptide of collagen type II, CPII; hyaluronic acid (HA); human cartilage
      glycoprotein 39, YKL-40; cartilage oligomeric matrix protein; and cathepsin K
      were analyzed in 48 OA patients and 52 healthy controls carrying the haplogroups
      H and J. Logistic regression models and receiver operating characteristic (ROC)
      curves were performed to predict the onset of OA. RESULTS: MMP-13 was the only
      biomarker significantly increased in OA patients compared to healthy controls in
      both haplogroups H and J. The collagen type II biomarkers, Coll2-1, Coll2-1NO(2),
      the Coll2-1NO(2)/Coll2-1 ratio, C2C, CPII, and the C2C:CPII ratio were
      significantly increased in OA patients carrying haplogroup H compared to OA
      carriers of the haplogroup J. Two logistic regression models for diagnosis were
      constructed and adjusted for age, gender, and body mass index. For haplogroup H,
      the biomarkers significantly associated with OA were MMP-13 and Coll2-1; the area
      under the curve (AUC) of the ROC curve for this model was 0.952 (95% CI = 0.892
      1.012). For haplogroup J, the only biomarker significantly associated with OA was
      MMP-13; the AUC for this model was 0.895 (95% CI = 0.801-0.989). CONCLUSION: The
      mitochondrial DNA haplogroups are potential complementary candidates for
      biomarkers of OA; their genotyping in conjunction with the assessment of
      classical protein molecular markers is recommended.

PMID- 22593744
TI  - Trial-by-Trial Adjustments of Cognitive Control Following Errors and Response
      Conflict are Altered in Pediatric Obsessive Compulsive Disorder.
AB  - BACKGROUND: Impairments of cognitive control have been theorized to drive the
      repetitive thoughts and behaviors of obsessive compulsive disorder (OCD) from
      early in the course of illness. However, it remains unclear whether altered trial
      by-trial adjustments of cognitive control characterize young patients. To test
      this hypothesis, we determined whether trial-by-trial adjustments of cognitive
      control are altered in children with OCD, relative to healthy controls. METHODS:
      Forty-eight patients with pediatric OCD and 48 healthy youth performed the Multi
      Source Interference Task. Two types of trial-by-trial adjustments of cognitive
      control were examined: post-error slowing (i.e., slower responses after errors
      than after correct trials) and post-conflict adaptation (i.e., faster responses
      in high-conflict incongruent trials that are preceded by other high-conflict
      incongruent trials, relative to low-conflict congruent trials). RESULTS: While
      healthy youth exhibited both post-error slowing and post-conflict adaptation,
      patients with pediatric OCD failed to exhibit either of these effects. Further
      analyses revealed that patients with low symptom severity showed a reversal of
      the post-conflict adaptation effect, whereas patients with high symptom severity
      did not show any post-conflict adaptation. CONCLUSION: Two types of trial-by
      trial adjustments of cognitive control are altered in pediatric OCD. These
      abnormalities may serve as early markers of the illness.

PMID- 22593745
TI  - Expression of Tight Junction and Drug Efflux Transporter Proteins in an in vitro
      Model of Human Blood-Brain Barrier.
AB  - Interendothelial cell tight junctions (TJs) proteins contribute to maintain the
      structural and functional integrity of the blood-brain barrier (BBB) and several
      efflux transporters regulate transport of compounds across BBB. A unique double
      compartment-model of the BBB, consisting of cerebral endothelial cells isolated
      from cryopreserved human glial tumors, alone and in the presence of human
      astroglial cells derived from the same tissue preparation was established.
      Endothelial cell viability and transendothelial electrical resistance (TEER) were
      measured in this model and three representative TJ proteins - occludin (OCLN),
      zonula occludens-1 (ZO-1) and claudin-5 (CLN-5) - as well as several drug efflux
      transporters - P-glycoprotein (P-gp), multidrug resistance protein-1 and 2 (MRP-1
      and MRP-2), organic anion-transporting polypeptide-1 and 3 (oatp1 and oatp3) were
      analyzed at both the protein and gene transcript level. Functional activity of P
      gp and MRP-1 was also assessed. Endothelial cell viability as well as TEER
      significantly increased in the presence of glial cells. A significant increase of
      expression of OCLN, ZO-1, and CLN-5 proteins as well as of several drug
      transporter proteins except oatp3 and MRP-1, was also found in the presence of
      glial cells. All the gene transcripts protein analyzed were found to be
      significantly increased in the presence of glial cells. A suitable functional
      activity of P-gp and MRP-1 was also found. These results demonstrate that this
      brain endothelium culture system mimics a physiologically relevant situation and
      may therefore provide a new tool for studying the effects of biological fluids
      such as serum and cerebrospinal fluid from patients with neurological disorders
      underlying a BBB alteration in disease pathogenesis.

PMID- 22593746
TI  - Are assumptions of well-known statistical techniques checked, and why (not)?
AB  - A valid interpretation of most statistical techniques requires that one or more
      assumptions be met. In published articles, however, little information tends to
      be reported on whether the data satisfy the assumptions underlying the
      statistical techniques used. This could be due to self-selection: Only
      manuscripts with data fulfilling the assumptions are submitted. Another
      explanation could be that violations of assumptions are rarely checked for in the
      first place. We studied whether and how 30 researchers checked fictitious data
      for violations of assumptions in their own working environment. Participants were
      asked to analyze the data as they would their own data, for which often used and
      well-known techniques such as the t-procedure, ANOVA and regression (or non
      parametric alternatives) were required. It was found that the assumptions of the
      techniques were rarely checked, and that if they were, it was regularly by means
      of a statistical test. Interviews afterward revealed a general lack of knowledge
      about assumptions, the robustness of the techniques with regards to the
      assumptions, and how (or whether) assumptions should be checked. These data
      suggest that checking for violations of assumptions is not a well-considered
      choice, and that the use of statistics can be described as opportunistic.

PMID- 22593747
TI  - A quantum probability model of causal reasoning.
AB  - People can often outperform statistical methods and machine learning algorithms
      in situations that involve making inferences about the relationship between
      causes and effects. While people are remarkably good at causal reasoning in many
      situations, there are several instances where they deviate from expected
      responses. This paper examines three situations where judgments related to causal
      inference problems produce unexpected results and describes a quantum inference
      model based on the axiomatic principles of quantum probability theory that can
      explain these effects. Two of the three phenomena arise from the comparison of
      predictive judgments (i.e., the conditional probability of an effect given a
      cause) with diagnostic judgments (i.e., the conditional probability of a cause
      given an effect). The third phenomenon is a new finding examining order effects
      in predictive causal judgments. The quantum inference model uses the notion of
      incompatibility among different causes to account for all three phenomena.
      Psychologically, the model assumes that individuals adopt different points of
      view when thinking about different causes. The model provides good fits to the
      data and offers a coherent account for all three causal reasoning effects thus
      proving to be a viable new candidate for modeling human judgment.

PMID- 22593748
TI  - The lateral occipital cortex in the face perception network: an effective
      connectivity study.
AB  - The perception of faces involves a large network of cortical areas of the human
      brain. While several studies tested this network recently, its relationship to
      the lateral occipital (LO) cortex known to be involved in visual object
      perception remains largely unknown. We used functional magnetic resonance imaging
      and dynamic causal modeling (DCM) to test the effective connectivity among the
      major areas of the face-processing core network and LO. Specifically, we tested
      how LO is connected to the fusiform face area (FFA) and occipital face area (OFA)
      and which area provides the major face/object input to the network. We found that
      LO is connected via significant bidirectional connections to both OFA and FFA,
      suggesting the existence of a triangular network. In addition, our results also
      suggest that face- and object-related stimulus inputs are not entirely segregated
      at these lower level stages of face-processing and enter the network via the LO.
      These results support the role of LO in face perception, at least at the level of
      face/non-face stimulus discrimination.

PMID- 22593749
TI  - Posttraumatic stress and myocardial infarction risk perceptions in hospitalized
      acute coronary syndrome patients.
AB  - Posttraumatic stress disorder (PTSD) is related to acute coronary syndrome (ACS;
      i.e., myocardial infarction or unstable angina) recurrence and poor post-ACS
      adherence to medical advice. Since risk perceptions are a primary motivator of
      adherence behaviors, we assessed the relationship of probable PTSD to ACS risk
      perceptions in hospitalized ACS patients (n = 420). Participants completed a
      brief PTSD screen 3-7 days post-ACS, and rated their 1-year ACS recurrence risk
      relative to other men or women their age. Most participants exhibited optimistic
      bias (mean recurrence risk estimate between "average" and "below average").
      Further, participants who screened positive for current PTSD (n = 15) showed
      significantly greater optimistic bias than those who screened negative (p <
      0.05), after adjustment for demographics, ACS severity, medical comorbidities,
      depression, and self-confidence in their ability to control their heart disease.
      Clinicians should be aware that psychosocial factors, and PTSD in particular, may
      be associated with poor adherence to medical advice due to exaggerated optimistic
      bias in recurrence risk perceptions.

PMID- 22593750
TI  - The fallacy of a "task-negative" network.

PMID- 22593751
TI  - Auditory evoked fields elicited by spectral, temporal, and spectral-temporal
      changes in human cerebral cortex.
AB  - Natural sounds contain complex spectral components, which are temporally
      modulated as time-varying signals. Recent studies have suggested that the
      auditory system encodes spectral and temporal sound information differently.
      However, it remains unresolved how the human brain processes sounds containing
      both spectral and temporal changes. In the present study, we investigated human
      auditory evoked responses elicited by spectral, temporal, and spectral-temporal
      sound changes by means of magnetoencephalography. The auditory evoked responses
      elicited by the spectral-temporal change were very similar to those elicited by
      the spectral change, but those elicited by the temporal change were delayed by 30
      50 ms and differed from the others in morphology. The results suggest that human
      brain responses corresponding to spectral sound changes precede those
      corresponding to temporal sound changes, even when the spectral and temporal
      changes occur simultaneously.

PMID- 22593752
TI  - Preclinical models to investigate retinal ischemia: advances and drawbacks.
AB  - Retinal ischemia is a major cause of blindness worldwide. It is associated with
      various disorders such as diabetic retinopathy, glaucoma, optic neuropathies,
      stroke, and other retinopathies. Retinal ischemia is a clinical condition that
      occurs due to lack of appropriate supply of blood to the retina. As the retina
      has a higher metabolic demand, any hindrance in the blood supply to it can lead
      to decreased supply of oxygen, thus causing retinal ischemia. The pathology of
      retinal ischemia is still not clearly known. To get a better insight into the
      pathophysiology of retinal ischemia, the role of animal models is indispensable.
      The standard treatment care for retinal ischemia has limited potential.
      Transplantation of stem cells provide neuroprotection and to replenish damaged
      cells is an emerging therapeutic approach to treat retinal ischemia. In this
      review we provide an overview of major animal models of retinal ischemia along
      with the current and preclinical treatments in use.

PMID- 22593754
TI  - Hypertrophy of the inferior olivary nucleus impacts perception of gravity.
AB  - Interruption of the dentato-olivary projections, interconnecting the dentate
      nucleus (DN) and the contralateral inferior olivary nucleus (ION), is predicted
      to interfere with the DN' role in estimating direction of gravity. In a patient
      with pendular nystagmus due to hypertrophy of the ION secondary to predominantly
      right-sided ponto-mesencephalic hemorrhage, perceived vertical shifted from
      clockwise to counter-clockwise deviations within 4 months. We hypothesize that
      synchronized oscillations of ION neurons induce a loss of inhibitory control,
      leading to hyperactivity of the contralateral DN and, as a result, to perceived
      vertical roll-tilt to the side of the over-active DN.

PMID- 22593753
TI  - High density electroencephalography in sleep research: potential, problems,
      future perspective.
AB  - High density EEG (hdEEG) during sleep combines the superior temporal resolution
      of EEG recordings with high spatial resolution. Thus, this method allows a
      topographical analysis of sleep EEG activity and thereby fosters the shift from a
      global view of sleep to a local one. HdEEG allowed to investigate sleep rhythms
      in terms of their characteristic behavior (e.g., the traveling of slow waves) and
      in terms of their relationship to cortical functioning (e.g., consciousness and
      cognitive abilities). Moreover, recent studies successfully demonstrated that
      hdEEG can be used to study brain functioning in neurological and neuro
      developmental disorders, and to evaluate therapeutic approaches. This review
      highlights the potential, the problems, and future perspective of hdEEG in sleep
      research.

PMID- 22593755
TI  - Differences between Early and Late-Onset Alzheimer's Disease in
      Neuropsychological Tests.
AB  - Although patients with Alzheimer disease (AD) share clinical and histological
      features regardless of age of onset, the hypothesis that early onset AD
      constitutes a distinct subgroup prevails. Some authors suggest that early
      attention or language impairment constitute patterns of differentiation in terms
      of neuropsychological profile, between these groups. However, investigations are
      not consensual in terms of cognitive domains affected in each group. AIM: To
      investigate whether there is early neuropsychological difference between two
      types of AD using the conventional dividing line of 65 years. METHODS: We
      evaluated the results obtained in the Mini-Mental State Examination (MMSE) and in
      a comprehensive neuropsychological battery - Battery of Lisbon for the Assessment
      of Dementia (BLAD), at a Dementia clinic in the University Hospital of Coimbra
      and a Memory Clinic. The study was developed in consecutive patients with a
      clinical probable diagnosis of mild to moderate AD, using standard criteria
      (DSMIV and NINCDS-ADRDA). Statistical analysis was performed using Qui-square and
      U-Mann-Whitney, for categorical and non-categorical variables. The degree of
      relation between variables, was measured using the coefficient of correlation
      r(s) de Spearman. RESULTS: The total sample included 280 patients: 109 with early
      onset AD and 171 with a late-onset form. Groups were comparable in terms of
      gender, education or severity of disease, and MMSE. In BLAD, for univariate
      analysis the early onset group had lower scores in Naming (p = 0.025), Right-Left
      Orientation (p = 0.029) and Praxis (p = 0.001), and better performances in
      Orientation (p = 0.001) and Visual Memory (p = 0.022). After application of
      Bonferroni correction for multiple comparisons only Praxis and Orientation could
      differentiate the two groups. No significant differences were found in other
      tests or functions. DISCUSSION: The results are suggestive of dissociated
      profiles between early and late-onset AD. Younger patients have a major
      impairment in Praxis and a tendency for a great impairment in neocortical
      temporal functions. AD patients with late-onset forms had a tendency for worse
      performances in Visual Memory and Orientation, suggesting a more localized
      disease to the limbic structures.

PMID- 22593756
TI  - The human intestinal IgA response; burning questions.
AB  - The title of this special topic invites us to identify areas in the field of IgA
      biology that are uncertain or in need of clarification. The inductive phase of
      the human intestinal IgA response has been a controversial area for some years.
      Therefore, to structure this review, we have identified key questions that are
      debated in this field. We have provided explanations of the origins of the
      uncertainties and have provided our own reasoned answers to the questions we
      pose.

PMID- 22593758
TI  - The immune response to sand fly salivary proteins and its influence on leishmania
      immunity.
AB  - Leishmaniasis is a vector-borne disease transmitted by bites of phlebotomine sand
      flies. During Leishmania transmission, sand fly saliva is co-inoculated with
      parasites into the skin of the mammalian host. Sand fly saliva consists of
      roughly thirty different salivary proteins, many with known roles linked to blood
      feeding facilitation. Apart from the anti-hemostatic capacity of saliva, several
      sand fly salivary proteins have been shown to be immunogenic. Immunization with a
      single salivary protein or exposure to uninfected bites was shown to result in a
      protective immune response against leishmaniasis. Antibodies to saliva were not
      required for this protection. A strong body of evidence points to the role for
      saliva-specific T cells producing IFN-gamma in the form of a delayed-type
      hypersensitivity reaction at the bite site as the main protective response.
      Herein, we review the immunity to sand fly salivary proteins in the context of
      its vector-parasite-host combinations and their vaccine potential, as well as
      some recent advances to shed light on the mechanism of how an immune response to
      sand fly saliva protects against leishmaniasis.

PMID- 22593759
TI  - Compatibility and kidney transplantation: the way to go.
AB  - Long lasting debates in the past questioned the relevance of any sort of
      compatibility in post mortal kidney transplantation. It is for no say that fully
      compatible transplants have the highest chances for a long patient and graft
      survival. In the present report the use of HLA-DR as a representative of the
      Major Histocompatibility Complex class II genes in the allocation of organs is
      discussed. The major arguments are the easiness to offer to patients a compatible
      graft in a relatively short waiting time, an increase in graft survival, the less
      sensitization during the transplantation period, and the lower waiting time for a
      retransplant. Even if the number of organ donors remains the same a lowering of
      the mean waiting time is expected because of the longer period of graft survival.

PMID- 22593757
TI  - Altered tryptophan metabolism as a paradigm for good and bad aspects of immune
      privilege in chronic inflammatory diseases.
AB  - The term "immune privilege" was coined to describe weak immunogenicity (hypo
      immunity) that manifests in some transplant settings. We extended this concept to
      encompass hypo-immunity that manifests at local sites of inflammation relevant to
      clinical diseases. Here, we focus on emerging evidence that enhanced tryptophan
      catabolism is a key metabolic process that promotes and sustains induced immune
      privilege, and discuss the implications for exploiting this knowledge to improve
      treatments for hypo-immune and hyper-immune syndromes using strategies to
      manipulate tryptophan metabolism.

PMID- 22593760
TI  - IL-13 Signaling in Liver Fibrogenesis.
AB  - Liver fibrosis is the final common pathway of chronic liver diseases irrespective
      of etiology. However, etiology deeply impacts progression and characteristics of
      liver fibrogenesis. IL-13 is the dominant pro-fibrotic cytokine in
      Schistosomiasis associated liver fibrogenesis. In vitro, IL-13 directly induces
      expression of fibrosis-associated genes, e.g., collagens or connective tissue
      growth factor, in hepatic stellate cells. Recently, potential effects of IL-13 in
      non-Schistosomiasis associated liver fibrosis have been uncovered. This review
      summarizes the potential roles of IL-13 in chronic liver disease of different
      etiologies, and the downstream events mediating IL-13 signaling in liver
      fibrogenesis.

PMID- 22593762
TI  - Biological robustness: paradigms, mechanisms, and systems principles.
AB  - Robustness has been studied through the analysis of data sets, simulations, and a
      variety of experimental techniques that each have their own limitations but
      together confirm the ubiquity of biological robustness. Recent trends suggest
      that different types of perturbation (e.g., mutational, environmental) are
      commonly stabilized by similar mechanisms, and system sensitivities often display
      a long-tailed distribution with relatively few perturbations representing the
      majority of sensitivities. Conceptual paradigms from network theory, control
      theory, complexity science, and natural selection have been used to understand
      robustness, however each paradigm has a limited scope of applicability and there
      has been little discussion of the conditions that determine this scope or the
      relationships between paradigms. Systems properties such as modularity, bow-tie
      architectures, degeneracy, and other topological features are often positively
      associated with robust traits, however common underlying mechanisms are rarely
      mentioned. For instance, many system properties support robustness through
      functional redundancy or through response diversity with responses regulated by
      competitive exclusion and cooperative facilitation. Moreover, few studies compare
      and contrast alternative strategies for achieving robustness such as homeostasis,
      adaptive plasticity, environment shaping, and environment tracking. These
      strategies share similarities in their utilization of adaptive and self
      organization processes that are not well appreciated yet might be suggestive of
      reusable building blocks for generating robust behavior.

PMID- 22593761
TI  - The Fyn-STAT5 Pathway: A New Frontier in IgE- and IgG-Mediated Mast Cell
      Signaling.
AB  - Mast cells are central players in immune surveillance and activation, positioned
      at the host-environment interface. Understanding the signaling events controlling
      mast cell function, especially those that maintain host homeostasis, is an
      important and still less understood area of mast cell-mediated disease. With
      respect to allergic disease, it is well established that IgE and its high
      affinity receptor FcepsilonRI are major mediators of mast cell activation.
      However, IgG-mediated signals can also modulate mast cell activities. Signals
      elicited by IgG binding to its cognate receptors (FcgammaR) are the basis for
      autoimmune disorders such as lupus and rheumatoid arthritis. Using knowledge of
      IgE-mediated mast cell signaling, recent work has begun to illuminate potential
      overlap between FcepsilonRI and FcgammaR signal transduction. Herein we review
      the importance of Src family kinases in FcepsilonRI and FcgammaR signaling, the
      role of the transcription factor STAT5, and impingement of the regulatory
      cytokines IL-4, IL-10, and TGFbeta1 upon this network.

PMID- 22593763
TI  - The use of next-generation sequencing in movement disorders.
AB  - New advances in genomic technology are being introduced at a greater speed and
      are revolutionizing the field of genetics for both complex and Mendelian
      diseases. For instance, during the past few years, genome-wide association
      studies (GWAS) have identified a large number of significant associations between
      genomic loci and movement disorders such as Parkinson's disease and progressive
      supranuclear palsy. GWAS are carried out through the use of high-throughput SNP
      genotyping arrays, which are also used to perform linkage analyses in families
      previously considered statistically underpowered for genetic analyses. In
      inherited movement disorders, using this latter technology, it has repeatedly
      been shown that mutations in a single gene can lead to different phenotypes,
      while the same clinical entity can be caused by mutations in different genes.
      This is being highlighted with the use of next-generation sequencing technologies
      and leads to the search for genes or genetic modifiers that contribute to the
      phenotypic expression of movement disorders. Establishing an accurate genome
      epigenome-phenotype relationship is becoming a major challenge in the post
      genomic research that should be facilitated through the implementation of both
      functional and cellular analyses.

PMID- 22593765
TI  - Comparison between Two Different Two-Stage Transperineal Approaches to Treat
      Urethral Strictures or Bladder Neck Contracture Associated with Severe Urinary
      Incontinence that Occurred after Pelvic Surgery: Report of Our Experience.
AB  - Introduction. The recurrence of urethral/bladder neck stricture after multiple
      endoscopic procedures is a rare complication that can follow prostatic surgery
      and its treatment is still controversial. Material and Methods. We
      retrospectively analyzed our data on 17 patients, operated between September 2001
      and January 2010, who presented severe urinary incontinence and urethral/bladder
      neck stricture after prostatic surgery and failure of at least four conservative
      endoscopic treatments. Six patients underwent a transperineal urethrovesical
      anastomosis and 11 patients a combined transperineal suprapubical (endoscopic)
      urethrovesical anastomosis. After six months the patients that presented complete
      incontinence and no urethral stricture underwent the implantation of an
      artificial urethral sphincter (AUS). Results. After six months 16 patients were
      completely incontinent and presented a patent, stable lumen, so that they
      underwent an AUS implantation. With a mean followup of 50.5 months, 14 patients
      are perfectly continent with no postvoid residual urine. Conclusions. Two-stage
      procedures are safe techniques to treat these challenging cases. In our opinion,
      these cases could be managed with a transperineal approach in patients who
      present a perfect operative field; on the contrary, in more difficult cases, it
      would be preferable to use the other technique, with a combined transperineal
      suprapubical access, to perform a pull-through procedure.

PMID- 22593764
TI  - Focal therapy in the management of prostate cancer: an emerging approach for
      localized prostate cancer.
AB  - A widespread screening with prostate-specific antigen (PSA) has led increased
      diagnosis of localized prostate cancer along with a reduction in the proportion
      of advanced-stage disease at diagnosis. Over the past decade, interest in focal
      therapy as a less morbid option for the treatment of localized low-risk prostate
      cancer has recently been renewed due to downward stage migration. Focal therapy
      stands midway between active surveillance and radical treatments, combining
      minimal morbidity with cancer control. Several techniques of focal therapy have
      potential for isolated ablation of a tumor focus with sparing of uninvolved
      surround tissue demonstrating excellent short-term cancer control and a favorable
      patient's quality of life. However, to date, tissue ablation has mostly used for
      near-whole prostate gland ablation without taking advantage of accompanying the
      technological capabilities. The available ablative technologies include
      cryotherapy, high-intensity focused ultrasound (HIFU), and vascular-targeted
      photodynamic therapy (VTP). Despite the interest in focal therapy, this
      technology has not yet been a well-established procedure nor provided sufficient
      data, because of the lack of randomized trial comparing the efficacy and
      morbidity of the standard treatment options. In this paper we briefly summarize
      the recent data regarding focal therapy for prostate cancer and these new
      therapeutic modalities.

PMID- 22593766
TI  - Enchondroma versus Low-Grade Chondrosarcoma in Appendicular Skeleton: Clinical
      and Radiological Criteria.
AB  - Objectives. To determine the validity of clinical and radiological features of
      enchondroma and low grade chondrosarcoma, and contrast the biopsy results with
      the clinical diagnosis based on the history and imaging. Material and Method. The
      study included 96 patients with cartilage type lesions suggestive of an
      enchondroma (E) or an low grade chondrosarcoma (LGC) according to the clinical
      and imaging data. The hypotheses were contrasted with the biopsy. Results. Of the
      82 patients studied completely, 56 were considered E (68.29%), 8 as LGC (8.33%)
      and in 18 (18.75%) were doubtful cases and considered as suspected LGC. Of these,
      the biopsy showed 4 E (25%), 10 LGC (50%) and 4 were not definitive. On the other
      hand, of the 56 cases diagnosed as E, 15 were biopsied, 5 of these biopsies
      turned out to be LGC (33.3%). The 8 cases diagnosed as LGC, were also biopsied
      and only 4 biopsies (50%) confirmed the initial diagnosis. Features analyzed in
      the study showed no statistically significant difference. Correlation analysis
      between the diagnosis issued initially and the biopsy result gave a value of 0.69
      (kappa coefficient), which was considered a good correlation. Conclusion.
      Features analyzed did not have any statistical significance. However, there was a
      good correlation between initial diagnosis and biopsy's result.

PMID- 22593767
TI  - Lysophosphatidic Acid disrupts junctional integrity and epithelial cohesion in
      ovarian cancer cells.
AB  - Ovarian cancer metastasizes via exfoliation of free-floating cells and
      multicellular aggregates from the primary tumor to the peritoneal cavity. A key
      event in EOC metastasis is disruption of cell-cell contacts via modulation of
      intercellular junctional components including cadherins. Ascites is rich in
      lysophosphatidic acid (LPA), a bioactive lipid that may promote early events in
      ovarian cancer dissemination. The objective of this paper was to assess the
      effect of LPA on E-cadherin junctional integrity. We report a loss of junctional
      E-cadherin in OVCAR3, OVCA429, and OVCA433 cells exposed to LPA. LPA-induced loss
      of E-cadherin was concentration and time dependent. LPA increased MMP-9
      expression and promoted MMP-9-catalyzed E-cadherin ectodomain shedding. Blocking
      LPA receptor signaling inhibited MMP-9 expression and restored junctional E
      cadherin staining. LPA-treated cells demonstrated a significant decrease in
      epithelial cohesion. Together these data support a model wherein LPA induces MMP
      9 expression and MMP-9-catalyzed E-cadherin ectodomain shedding, resulting in
      loss of E-cadherin junctional integrity and epithelial cohesion, facilitating
      metastatic dissemination of ovarian cancer cells.

PMID- 22593768
TI  - EBV Reactivation and Chromosomal Polysomies: Euphorbia tirucalli as a Possible
      Cofactor in Endemic Burkitt Lymphoma.
AB  - Burkitt lymphoma is endemic in the Equatorial Belt of Africa, its molecular
      hallmark is an activated, MYC gene mostly due to a chromosomal translocation.
      Especially in its endemic clinical variant, Burkitt lymphoma is associated with
      the oncogenic Epstein-Barr virus (EBV), and holoendemic malaria acts as an
      amplifier. Environmental factors may also cooperate in Burkitt lymphomagenesis in
      the endemic regions, such as plants used as traditional herbal remedies.
      Euphorbia tirucalli, a plant known to possess EBV-activating substances, has a
      similar geographical distribution to endemic Burkitt's Lymphoma and is used as a
      hedge, herbal remedy and toy in the Lymphoma BeltI. In this study we aimed at
      determining if exposure to Euphorbia tirucalli could contribute to
      lymphomagenesis, and at which extent. Lymphoblastoid and cord blood-derived cell
      lines were treated with plant extracts, and the expression of EBV-coded proteins
      was checked, to assess EBV reactivation. The occurrence of chromosomal
      translocations was then investigated by FISH. Our preliminary results suggest
      that E. tirucalli is able to reactivate EBV and determine chromosomal
      alterations, which leads to c-MYC altered expression. The existence of genomic
      alterations might determine the accumulation of further genetic alteration, which
      could eventually lead to a transformed phenotype.

PMID- 22593770
TI  - Aquatic exercise is effective in improving exercise performance in patients with
      heart failure and type 2 diabetes mellitus.
AB  - Background. Peak oxygen uptake (VO(2peak)) and muscle function are more decreased
      in patients with a combination of chronic heart failure (CHF) and type 2 diabetes
      mellitus (2DM) compared to patients with only one of the conditions. Further,
      patients with 2DM have peripheral complications that hamper many types of
      conventional exercises. Aim. To evaluate the efficacy and applicability of eight
      week aquatic exercise in patients with the combination of CHF and 2DM. Methods.
      Twenty patients (four women) with both CHF and 2DM (age 67.4 +/- 7.1, NYHA II
      III) were randomly assigned to either aquatic exercise or a control group. The
      patients exercised for 45 minutes 3 times/week in 33-34 degrees C, swimming pool.
      Results. The training programme was well tolerated. Work rate (+11.7 +/- 6.6
      versus -6.4 +/- 8.1 watt, P < 0.001) and VO(2peak) (+2.1 +/- 0.8 versus -0.9 +/-
      1.4 mL.kg(-1).min(-1), P < 0.001) and walking capacity (P = 0.01) increased
      significantly in the training group. Muscle function was also significantly
      improved and Hba1c decreased significantly (P < 0.01) during training, while
      fasting glucose, insulin, c-peptide, and lipids were unchanged . Training also
      increased vitality measured by SF-36 significantly (P = 0.05). Conclusion.
      Aquatic exercise could be used to improve exercise capacity and muscle function
      in patients with the combination of CHF and 2DM.

PMID- 22593771
TI  - Gastric variceal bleeding caused by an intrahepatic arterioportal fistula that
      formed after liver biopsy: a case report and review of the literature.
AB  - An intrahepatic arterioportal fistula is a rare cause of portal hypertension and
      variceal bleeding. We report on a patient with an intrahepatic arterioportal
      fistula following liver biopsy who was successfully treated by hepatectomy after
      unsuccessful arterial embolization. We also review the literature on symptomatic
      intrahepatic arterioportal fistulas after liver biopsy. A 48-year-old male with
      bleeding gastric varices and hepatitis B virus-associated liver cirrhosis was
      transferred to our hospital; this patient previously underwent percutaneous liver
      biopsies 3 and 6 years ago. Abdominal examination revealed a bruit over the
      liver, tenderness in the right upper quadrant, and splenomegaly. Ultrasonographic
      examination, computed tomography, and angiography confirmed an arterioportal
      fistula between the right hepatic artery and the right portal vein with portal
      hypertension. After admission, the patient suffered a large hematemesis and
      developed shock. He was treated with emergency transarterial embolization using
      microcoils. Since some collateral vessels bypassed the obstructive coils and
      still fed the fistulous area, embolization was performed again. Despite the
      second embolization, the collateral vessels could not be completely controlled.
      Radical treatment involving resection of his right hepatic lobe was performed.
      For nearly 6 years postoperatively, this patient has had no further episodes of
      variceal bleeding. 

PMID- 22593769
TI  - Recurrent herpetic stromal keratitis in mice: a model for studying human HSK.
AB  - Herpes simplex virus 1 (HSV-1) infection of the cornea leads to a potentially
      blinding disease, termed herpetic stromal keratitis (HSK) that is characterized
      by lesions of an immunoinflammatory nature. In spite of the fact that HSK
      typically presents as a recurrent disease due to reactivation of virus which
      latently infects the trigeminal ganglia, most murine studies of HSK have employed
      a primary and not recurrent model of the disease. This report documents the
      several recurrent models of HSK that have been developed and how data generated
      from these models differs in some important aspects from data generated following
      primary infection of the cornea. Chief among these differences is the fact that
      recurrent HSK takes place in the context of an animal that has a preexisting anti
      HSV immune response, while primary HSK occurs in an animal that is developing
      such a response. We will document both differences and similarities that derive
      from this fundamental difference in these models with an eye towards possible
      vaccines and therapies that demonstrate promise in treating HSK.

PMID- 22593772
TI  - Efficacy of pegylated interferon plus ribavirin in combination with
      corticosteroid for two cases of combined hepatitis C and autoimmune hepatitis.
AB  - The treatment strategy for cases of combined autoimmune hepatitis (AIH) and
      chronic hepatitis C (CHC) has not yet been established. A 47-year-old woman and a
      53-year-old-woman were hospitalized for treatment of CHC. Ultrasonography and
      histological findings revealed that their liver was not cirrhotic but did have
      chronic damage. The histological findings of both patients were suggestive of
      AIH. The patients were systematically treated with pegylated interferon-alpha 2b
      plus ribavirin which was preceded by and combined with corticosteroid (CS), and
      showed sustained virological responses and normal liver function. Although these
      two patients with combined AIH and CHC were successfully treated with this
      regimen, careful attention to exacerbation of hepatic inflammation is needed
      because hepatitis C viral load was increased due to immunosuppression during CS
      treatment. 

PMID- 22593773
TI  - Early Social Cognition: Alternatives to Implicit Mindreading.
AB  - According to the BD-model of mindreading, we primarily understand others in terms
      of beliefs and desires. In this article we review a number of objections against
      explicit versions of the BD-model, and discuss the prospects of using its
      implicit counterpart as an explanatory model of early emerging socio-cognitive
      abilities. Focusing on recent findings on so-called 'implicit' false belief
      understanding, we put forward a number of considerations against the adoption of
      an implicit BD-model. Finally, we explore a different way to make sense of
      implicit false belief understanding in terms of keeping track of affordances.

PMID- 22593774
TI  - [Cardiothyreosis at the University Hospital of Bobo-Dioulasso, Burkina Faso].

PMID- 22593775
TI  - A pharmacovigilance study of adults on highly active antiretroviral therapy,
      South Africa: 2007 - 2011.
AB  - BACKGROUND: Of the 1.6 million South African people infected with human
      immunodeficiency virus (HIV), approximately 970,000 (55%) have been initiated on
      HAART. Despite these numbers, very little has been published about the safety
      profile of antiretroviral (ARV) medicines in the country. This study was
      performed at the Medunsa National Pharmacovigilance Centre and aimed to describe
      the demographic characteristics of patients enrolled in the pharmacovigilance
      surveillance study; highly active antiretroviral therapy (HAART) initiation
      regimen patterns; reasons for regimen changes; and adverse effects of ARV
      medicines. METHODS: A cohort study of HIV-infected individuals aged 15 years or
      older who were on ARV medicines was conducted at four sentinel sites. RESULTS:
      After HAART initiation, with an average lapse of 17.8 months (range: 0 - 83.8
      months), 2,815 patients were enrolled into the study. Results show that patients
      were observed for 1,606.2 person-years for pharmacy visits (collection of ARV
      medicines) and 817.1 person-years for clinical visits (consultation with the
      doctor). Females constituted 69.6% (1,958/2,815) of the study population. Almost
      all patients initiated HAART on first-line regimens (2,801/2,815). Some patients
      (6.7%, 190/2,815) dropped out of the study after HAART initiation. Reasons for
      regimen changes were not recorded for 2.5% (22/891) of the patients who changed
      regimens. The primary reason for regimen changes was drug-related toxicity
      (76.1%, 678/891), mostly evident in patients taking first-line regimens. Adverse
      effects experienced by patients were polyneuropathy (24.0%, 163/678);
      lipodystrophy (23.9%, 162/678); neuropathy (10.6%, 72/678); and suspected lactic
      acidosis (3.8%, 26/678). CONCLUSION: The majority of prescribers complied with
      the HAART guidelines and initiated most patients on first-line regimens. However,
      adverse effects are evident in patients taking first-line regimens. We recommend
      that the Department of Health should introduce less toxic first-line ARV
      regimens. Future efforts will aim to initiate patients on HAART and enrol them
      into the study simultaneously to determine early risk profiles of ARV medicines.

PMID- 22593776
TI  - [Acute intestinal obstruction in pregnancy - about five cases].

PMID- 22593777
TI  - [Infectious peritonitis in continuous ambulatory peritoneal dialysis at Rabat
      University Hospital: bacteriological profile over three years].

PMID- 22593778
TI  - [Escherichia coli thyroid abscess: report of a case and literature review].

PMID- 22593779
TI  - [Ileosigmoid knot: report of 2 cases].

PMID- 22593780
TI  - [Atypical clinical presentation of a primitive thymic hydatid cyst: about a
      Moroccan observation].

PMID- 22593781
TI  - Competence of health care providers on care of newborns at birth in a level-1
      health facility in Yaounde, Cameroon.
AB  - INTRODUCTION: This is an observational study which was carried out at a level one
      health facility in Yaounde from June to July 2009. The aim was to evaluate the
      competence of health care providers towards newborns' care at birth METHODS: Ten
      health care providers took care of three hundred and thirty-five pregnant women
      who were enrolled for the study after informed verbal consent in the delivery
      room. RESULTS: Out of 340 offspring delivered and taken care of, 179 (52.6%) were
      male and 161 (47.4%) were female. Only two out of ten health workers had a WHO
      Essential Newborn Care (ENC) training. None of them had received any refresher
      course for the past two years. The mean gestational age of women was 39.5 +/- 3.5
      weeks. Resuscitation was carried out on 21 (6.2%) of the newborns including 7
      (33.3%) who had birth asphyxia. Health care providers scored 100% in performing
      the following tasks: warming up the baby, applying eye drops, injecting vitamin
      K, identifying the neonate, searching for any apparent life threatening
      congenital malformations, preventing for infection after procedures and
      initiating breastfeeding. The score was 24% at neonatal resuscitation tasks. Low
      level of education was associated with poor competence on applying ENC tasks
      (p<0.001). Lack of WHO ENC training was associated with poor competence on ENC
      tasks (p<0.001) and poor skills on resuscitation (p=0.03). CONCLUSION: There is a
      need to reinforce the capacity of health care providers by training in WHO ENC
      course with emphasis on providing skills on resuscitation in order to reduce the
      burden of neonatal intrapartum-related deaths.

PMID- 22593782
TI  - Blood Magnesium levels in migraineurs within and between the headache attacks: a
      case control study.
AB  - INTRODUCTION: Some probable mechanisms have been described to the relationship
      between magnesium (Mg) level and migraine headache attacks. In the study reported
      here, we sought to determine the total Mg serum status of patients with migraine
      within and between the headache attacks and compare it with non-migraineurs.
      METHODS: This study was performed on 50 migraineurs patients diagnosed according
      to the International Headache Society (IHS) criteria for acute migraine headache.
      Fifty healthy subjects without any family history or evidences of migraine were
      randomly selected from hospital personnel as the control group. Serum Mg level
      was measured by Xylidyl blue method. RESULTS: In the group with migraine
      headache, no significant difference was found in the serum total Mg levels within
      and between migraine headache attacks (1.86 +/- 0.41 mg/dl versus 1.95 +/- 0.35
      mg/dl, p = 0.224). But, serum total Mg level was notably lower in the group with
      these attacks compared to the control group (1.86 +/- 0.41 mg/dl versus 2.10 +/-
      0.23 mg/dl, p < 0.001). CONCLUSION: Serum Mg level is on average significantly
      reduced in patients with migraine compared to the healthy group. However, the
      serum total Mg levels in migraineurs remained constant within and between
      migraine headache attacks.

PMID- 22593783
TI  - Tubercular endometritis detected through Pap smear campaign in Enugu, Nigeria.
AB  - In a series of 3,267 cervical smears examined in Enugu, Nigeria, from 1993
      through 2010, there was a single positive case of tuberculosis (TB). It was found
      in a 55-year-old, Para 7, postmenopausal woman. Treatment for tuberculosis was
      instituted successfully.

PMID- 22593784
TI  - [Diaphragmatic strangulated Bochdalek hernia: a rare cause of intestinal
      obstruction].

PMID- 22593785
TI  - Sudden onset methaemoglobinaemia in a previously well Ugandan child: a case
      report and literature review.
AB  - Methaemoglobinaemia is a rare condition of unknown prevalence. Diagnostic tests
      in resource limited settings are very rare but clinical signs can be a good
      guide. We set out to describe a case of Methaemoglobinaemia, raise awareness
      among practitioners in resource limited settings and to share experiences in its
      diagnosis and management. A previously well three and a half year old girl was
      admitted with central cyanosis of sudden onset. She underwent clinical,
      laboratory and radiological evaluation. Having been in a resource limited
      setting, the process of making a diagnosis was slow and difficult. After the
      diagnosis, the treatment was not available in the country but we managed to get
      it all the way from Nairobi, Kenya. A diagnosis of Methaemoglobinaemia was made
      using Spectrophotometry and she was successfully treated using 2 doses of
      intravenous Methylene blue. The cause of Methaemoglobinaemia was established to
      have been nitrites from food preservatives.

PMID- 22593786
TI  - TB case detection: can we remain passive while the process is active?
AB  - TB remains a major public health problem despite all the efforts that have been
      made since it was declared a global emergency in 1993. Different strategies have
      been implemented to curb the spread of the epidemic. Early case detection and
      treatment is one of the pillars of the TB control program. In 1991, WHO set
      targets for increasing case detection and treatment success rates to 70% and 85%
      respectively. Although the target of treatment success rate has been achieved,
      the case detection rate remains far below target at currently less than 50%. It
      is high time that control programs move from simple passive to a more systematic
      active case finding in order to accelerate TB control.

PMID- 22593787
TI  - A comparative study of the socioeconomic factors associated with childhood sexual
      abuse in sub-Saharan Africa.
AB  - BACKGROUND: Childhood sexual abuse (CSA) is a problem of considerable proportion
      in Africa where up to one-third of adolescent girls report their first sexual
      experience as being forced. The impact of child hood sexual abuse resonates in
      all areas of health. The aim of this study was to describe the prevalence of
      childhood sexual abuse and variations across socioeconomic status in six sub
      Saharan countries. METHODS: Datasets from Demographic and Health Surveys (DHS) in
      six sub-Saharan African countries conducted between 2003 and 2007 were used to
      access the relationship between CSA and socio economic status using multiple
      logistic regression models. RESULTS: There was no association between CSA and
      education, wealth and area of settlement. However, there was contrasting
      association between CSA and working status of women. CONCLUSION: This study
      concurs with other western studies which indicate that CSA transcends across all
      socio economic group. It is therefore important that effective preventive
      strategies are developed and implemented that will cross across all socio
      economic groups.

PMID- 22593788
TI  - Hypertension and type 2 diabetes: a cross-sectional study in Morocco (EPIDIAM
      Study).
AB  - BACKGROUND: In Morocco, there are no studies that focused on the hypertension and
      its associated risk factors through patients with type 2 diabetes. Different
      findings show that the frequency of type 2 diabetes has risen rapidly in Morocco.
      The main objective of this study was to assess the prevalence of hypertension and
      its associated risk factors among a group of patients with type 2 diabetes and to
      examine the level of control of hypertension among type 2 diabetic patients with
      hypertension. METHODS: A cross-sectional study was carried out on 525 type 2
      diabetics in three Moroccan regions. The structured questionnaire was used to
      gather information on sociodemographic variables, history of hypertension, use of
      anti-hypertensive medications and duration of diabetes. Anthropometric
      measurements including weight and height were measured by trained staff. Blood
      pressure was measured using standardized sphygmomanometers. RESULTS: The
      prevalence of hypertension was 70.4%. The logistic regression indicated that
      hypertension was positively associated with age (p<10-4), BMI (p<0.0002) and
      duration of diabetes (p) CONCLUSION: Hypertension is a common co-morbidity among
      Moroccan diabetic patients with high rate of ignorance of hypertension among
      study subjects. The focus must be on patients and family education, counseling
      and behavioral interventions designed to modify lifestyle such as increasing
      physical activity and adopting recommended dietary changes, as well as compliance
      with medications.

PMID- 22593789
TI  - [Tuberculosis of the midfoot, an unusual location: report of a case].

PMID- 22593790
TI  - Management of penetrating cardiac injuries in the Department of surgery, Mohamed
      Thahar Maamouri Hospital, Tunisia: report of 19 cases.
AB  - The goal of this paper is to discuss how to ameliorate the management of
      penetrating cardiac injuries in general surgery department. An algorithm for the
      initial assessment of penetrating injuries in cardiac box, based on our own
      experience, is presented. This was a retrospective study of 19 patients
      undergoing thoracotomy for penetrating cardiac injuries, managed in the
      department of general surgery of Nabeul-Tunisia, between 1994 and 2010. The mean
      age of patients was 25 years old. Sex ratio was 8,5. All patients had cardiac
      injury resulting from stab wounds inside of the pericardium. 42% of them were
      critically unstable, 21% had cardiac tamponnade. All these patients were quickly
      transferred to the operating room without any other investigations. 37% of
      patients were hemodynamically stable and underwent additional investigations. The
      management of penetrating cardiac injuries is possible in a general surgery
      department, but it requires a rapid prehospital transfer, a yet thorough physical
      examination along with efficient surgical management, all done in minimal time.

PMID- 22593791
TI  - Lassa fever: the challenges of curtailing a deadly disease.
AB  - Today Lassa fever is mainly a disease of the developing world, however several
      imported cases have been reported in different parts of the world and there are
      growing concerns of the potentials of Lassa fever Virus as a biological weapon.
      Yet no tangible solution to this problem has been developed nearly half a decade
      after its identification. Hence, the paper is aimed at appraising the problems
      associated with LAF illness; the challenges in curbing the epidemic and
      recommendations on important focal points. A Review based on the documents from
      the EFAS conference 2011 and literature search on PubMed, Scopus and Science
      direct. The retrieval of relevant papers was via the University of British
      Columbia and University of Toronto Libraries. The two major search engines
      returned 61 and 920 articles respectively. Out of these, the final 26 articles
      that met the criteria were selected. Relevant information on epidemiology, burden
      of management and control were obtained. Prompt and effective containment of the
      Lassa fever disease in Lassa village four decades ago could have saved the West
      African sub-region and indeed the entire globe from the devastating effect and
      threats posed by this illness. That was a hard lesson calling for much more
      proactive measures towards the eradication of the illness at primary, secondary
      and tertiary levels of health care.

PMID- 22593792
TI  - [Primary pulmonary Non-Hodgkin's lymphoma: report of a case].

PMID- 22593793
TI  - [Preserving vascular asset in Ibn Sina Teaching Hospital, Rabat-Morocco: the role
      of the nurse].

PMID- 22593794
TI  - Osteomalacia associated with cutaneous psoriasis as the presenting feature of
      coeliac disease: a case report.
AB  - Celiac disease (CD) is a chronic digestive disease that results in
      hypersensitivity to the gliadin fraction of Gluten. Malabsorption syndrome may be
      responsible for weight loss, diarrhea, osteomalacia, and vitamins deficiency.
      Herein we report a patient with coeliac disease (CD) who presented with
      osteomalacia and psoriasis without classical symptoms of CD. A 25-year-old North
      African Tunisian white woman was admitted to the hospital because of a 1-year
      history of bone pain, weight loss and weakness. She had cutaneous psoriasis on
      dermatologic examination. She had also anemia, hypocalcemia and pathological
      fracture. She was diagnosed to have osteomalacia on the basis of clinical,
      biological and radiological findings. Further investigations revealed the
      presence of antiglutaminase antibodies, and histopathologic findings of the
      duodenal biopsy were consistent with celiac disease. The patient showed a fast
      response to gluten-free diet, and full recovery with calcium and vitamin D
      replacement. Coeliac disease is frequently misdiagnosed leading to major
      complications such as osteolamacia. In the other hand, osteomalacia can still be
      the presenting feature of undiagnosed celiac disease. Association between
      osteomalacia and cutaneous psoriasis is rarely reported.

PMID- 22593795
TI  - [Peutz-Jeghers syndrome, about 3 cases in siblings].

PMID- 22593796
TI  - [Strangulation of the sigmoid colon by a giant ectopic testis].

PMID- 22593797
TI  - Exposure to blood among mortuary workers in teaching hospitals in south-west
      Nigeria.
AB  - BACKGROUND: Mortuary workers like other health workers are exposed to blood borne
      pathogens at work. A baseline assessment is important to plan for programmes to
      safeguard the health of workers. The aim of this study is to determine exposure
      rates to blood among mortuary workers in teaching hospitals in South West
      Nigeria. METHODS: A descriptive cross sectional study was carried out between
      March and May 2008. All mortuary workers working in six (6) teaching hospitals,
      80 in total were included in the study. Data was collected with the aid of a 15-
      item self administered questionnaire. Data was analysed with the aid of EPI-INFO
      2002. Statistical associations were explored using odds ratio and confidence
      intervals. RESULTS: A total of 76 respondents completed questionnaire giving a
      response rate of 95%; 3 males and 1 female declined to participate, the mean age
      of respondents was 38.2 years, 48(72.6%), 53(85.5%) and 50(73.5%) of the workers
      had been exposed to blood through cuts, blood splash and needle stick injury.
      Duration at work was significantly associated with blood splash. Workers who had
      worked 5 years and above were 0.10 times (95% confidence interval 0.00-.0.78) as
      likely to experience blood splash compared to those who had worked under 5 years.
      Only 5(10.4%) of workers with needle stick injury had completed three doses of
      Hepatitis B vaccine. The specific confirmation by antibody titre was however not
      done in this study. CONCLUSION: Exposure to blood was very common with blood
      splash emerging as the most common route of exposure. There is a need for
      vaccination of all mortuary workers with three doses of Hepatitis B Vaccine to
      protect their health. In addition, education of workers on risks and institution
      of standard operating procedure are crucial to safeguard the health of mortuary
      workers.

PMID- 22593798
TI  - Role of the cofilin activity cycle in astrocytoma migration and invasion.
AB  - The cofilin pathway plays a central role in the regulation of actin
      polymerization and the formation of cell membrane protrusions that are essential
      for cell migration. Overexpression of cofilin has been linked to the
      aggressiveness of a variety of different cancers. In these cancers, the
      phosphorylation of cofilin at Ser3 is a key regulatory mechanism modulating
      cofilin activity. The activation status of cofilin has been directly linked to
      tumor invasion. Accordingly, in this study, we examined the expression of cofilin
      and its activation status in astrocytoma cell lines and astrocytic tumors. We
      show that cofilin expression was increased and correlated with increasing grade
      malignant astrocytoma. In addition, both cofilin and LIMK had elevated expression
      in astrocytoma cell lines. Knockdown of cofilin by siRNA altered astrocytoma cell
      morphology and inhibited astrocytoma migration and invasion. Conversely,
      overexpression of a cofilin phosphorylation mutant in an in vivo intracranial
      xenograft model resulted in a more highly invasive phenotype than those
      xenographs expressing wild-type cofilin. Animals harboring astrocytomas stably
      expressing the cofilin phosphorylation mutant (cofilin-S3A) demonstrated marked
      local invasiveness and spread across the corpus callosum to the contralateral
      hemisphere in all animals. Taken together, these data indicate that the cofilin
      activity pathway may represent a novel therapeutic target to diminish the
      invasion of these highly malignant tumors.

PMID- 22593799
TI  - Exploring molecular pathways of triple-negative breast cancer.
AB  - Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with
      a high rate of proliferation and metastasis, as well as poor prognosis for
      advanced-stage disease. Although TNBC was previously classified together with
      basal-like and BRCA1/2-related breast cancers, genomic profiling now shows that
      there is incomplete overlap, with important distinctions associated with each
      subtype. The biology of TNBC is still poorly understood; therefore, to define the
      relative contributions of major cellular pathways in TNBC, we have studied its
      molecular signature based on analysis of gene expression. Comparisons were then
      made with normal breast tissue. Our results suggest the existence of molecular
      networks in TNBC, characterized by explicit alterations in the cell cycle, DNA
      repair, nucleotide synthesis, metabolic pathways, NF-kappaB signaling,
      inflammatory response, and angiogenesis. Moreover, we also characterized TNBC as
      a cancer of mixed phenotypes, suggesting that TNBC extends beyond the basal-like
      molecular signature and may constitute an independent subtype of breast cancer.
      The data provide a new insight into the biology of TNBC.

PMID- 22593800
TI  - HOXC8-Dependent Cadherin 11 Expression Facilitates Breast Cancer Cell Migration
      through Trio and Rac.
AB  - HOXC8 expression is upregulated in diverse cancer types, and a high level of
      HOXC8 is often associated with the aggressive/metastatic phenotypes. We
      previously reported that the presence of HOXC8 is essential for breast cancer
      cell migration and metastasis. However, the underlying molecular mechanism of
      HOXC8 regulation of cell migration is unclear. Here, we demonstrate that the
      presence of HOXC8 is required for cadherin 11 (CDH11) expression in breast cancer
      cells and that HOXC8 regulation of cell migration is mediated by CDH11. To
      understand the role of HOXC8-CDH11 axis in cell migration, we show that depleting
      either HOXC8 or CDH11 diminishes the formation of actin-based membrane ruffles,
      an event essential for cell migration. The loss of membrane ruffles in HOXC8- or
      CDH11-knockdown cells is apparently caused by reduced Rac activity because
      ectopically expressing active Rac1 restores cytoskeleton reorganization. CDH11
      physically interacts with Trio, a Rac GEF. We show that Trio is responsible for
      the majority of endogenous Rac activity in migratory breast cancer cells. Because
      knockdown of CDH11 prevents the plasma membrane localization of Trio, our study
      indicates that CDH11 may play a role in recruiting Trio to the plasma membrane
      where Trio activates Rac, leading to cell migration. This study reveals a novel
      HOXC8-CDH11-Trio-Rac signaling axis that contributes significantly to breast
      cancer cell migration.

PMID- 22593801
TI  - Activation of p21-Dependent G1/G2 Arrest in the Absence of DNA Damage as an
      Antiapoptotic Response to Metabolic Stress.
AB  - The folate enzyme, FDH (10-formyltetrahydrofolate dehydrogenase, ALDH1L1), a
      metabolic regulator of proliferation, activates p53-dependent G1 arrest and
      apoptosis in A549 cells. In the present study, we have demonstrated that FDH
      induced apoptosis is abrogated upon siRNA knockdown of the p53 downstream target
      PUMA. Conversely, siRNA knockdown of p21 eliminated FDH-dependent G1 arrest and
      resulted in an early apoptosis onset. The acceleration of FDH-dependent apoptosis
      was even more profound in another cell line, HCT116, in which the p21 gene was
      silenced through homologous recombination (p21(-/-) cells). In contrast to A549
      cells, FDH caused G2 instead of G1 arrest in HCT116 p21(+/+) cells; such an
      arrest was not seen in p21-deficient (HCT116 p21(-/-)) cells. In agreement with
      the cell cycle regulatory function of p21, its strong accumulation in nuclei was
      seen upon FDH expression. Interestingly, our study did not reveal DNA damage upon
      FDH elevation in either cell line, as judged by comet assay and the evaluation of
      histone H2AX phosphorylation. In both A549 and HCT116 cell lines, FDH induced a
      strong decrease in the intracellular ATP pool (2-fold and 30-fold, respectively),
      an indication of a decrease in de novo purine biosynthesis as we previously
      reported. The underlying mechanism for the drop in ATP was the strong decrease in
      intracellular 10-formyltetrahydrofolate, a substrate in two reactions of the de
      novo purine pathway. Overall, we have demonstrated that p21 can activate G1 or G2
      arrest in the absence of DNA damage as a response to metabolite deprivation. In
      the case of FDH-related metabolic alterations, this response delays apoptosis but
      is not sufficient to prevent cell death.

PMID- 22593802
TI  - Transcriptional Regulation of EGR1 by EGF and the ERK Signaling Pathway in
      Prostate Cancer Cells.
AB  - The early growth response gene 1, EGR1, is an important transcriptional regulator
      and acts as the convergent point between a variety of extracellular stimuli and
      activation of target genes. Unlike other tumor types, prostate tumors express
      high levels of EGR1 relative to normal tissues. However, the mechanism of EGR1
      regulation in prostate tumor cells is unknown. As EGR1 expression and epidermal
      growth factor (EGF) signaling are frequently upregulated in prostate tumors, we
      tested the hypothesis that EGF induces EGR1 expression in prostate cancer cells.
      Using RT-PCR to quantify EGR1 transcripts, we found that EGF induced EGR1
      expression in a dose- and time-dependent manner and the ERK pathway inhibitor,
      PD98059, abrogated the EGF-mediated EGR1 response in LNCaP and PC3 cells.
      Analysis of the EGR1 promoter using deletion constructs identified an EGF
      responsive region in the proximal promoter (-771 to -245 bp) containing 3
      potential serum response element (SRE) sites. In vivo chromatin
      immunoprecipitation assays demonstrated that Elk-1 binding at the SRE sites of
      the EGR1 promoter was enhanced by EGF treatment in PC3 cells. Overexpression of
      Elk-1 was sufficient to activate the EGF-responsive region of EGR1 promoter in
      PC3 cells and, similarly, a dominant-negative Elk-1 suppressed EGR1 promoter
      activity. Taken together, these results demonstrate for the first time that EGR1
      expression in PC3 cells is mediated through an EGF-ERK-Elk-1 signaling cascade.

PMID- 22593803
TI  - Loss of heterozygosity at the glutathione peroxidase 1 locus is not an early
      event in colon carcinogenesis.
AB  - It has been previously shown that loss of heterozygosity (LOH) at the cytosolic
      glutathione peroxidase (GPx-1) locus is a common event in the development of
      several cancer types, including colorectal cancer. GPx-1 is an antioxidant
      selenium-containing protein, and polymorphisms within this gene have been shown
      to be associated with the increased risk of cancer. In order to assess whether
      this genetic change was an early or late event in colon cancer development, we
      investigated whether LOH at this site was occurring in colorectal adenomas, a
      premalignant lesion. Twenty-four pairs of DNA samples, obtained from both whole
      blood and adenoma tissue from the same individuals, were genotyped at 2 positions
      in the GPx-1 gene: a codon 198 variation resulting in either a leucine or proline
      at the corresponding position in the peptide, or a variable number of alanine
      repeat codons corresponding to the amino terminus of the GPx-1 protein. No
      evidence of GPx-1 LOH was observed in the examined sample sets. These data
      indicate that the genetic loss at the GPx-1 locus may be a late event in colon
      carcinogenesis.

PMID- 22593804
TI  - Expression of Human Endogenous Retrovirus Type K Envelope Protein is a Novel
      Candidate Prognostic Marker for Human Breast Cancer.
AB  - We previously observed that the HERV type K (HERV-K) envelope (env) protein was
      expressed in the majority of human breast tumors from a U.S. cohort of women from
      Texas. We also made the preliminary observation that the expression of HERV-K env
      transcripts was associated with markers of disease progression. In this follow-up
      study, env protein expression was evaluated immunohistochemically in an
      additional 195 paraffin-embedded breast tumors from a second U.S. patient cohort
      (Baltimore, Maryland) and in 110 tumors from Chinese patients. Moreover, we
      compared env transcript expression between fresh-frozen normal and cancerous
      breast tissues. We observed that while env mRNA and protein expression was
      undetectable in normal breast tissue and in a subset of uninvolved normal
      appearing tissue adjacent to the tumor epithelium, it was overexpressed in most
      tumors. Furthermore, env expression was associated with breast cancer
      progression. In Baltimore cohort women, HERV-K tumor positivity was significantly
      associated with disease stage and lymph node metastasis. In Chinese women, HERV-K
      env positivity was significantly associated with tumor size, TNM stage, and lymph
      node metastases, which is consistent with the observations in the U.S. cohort. We
      also found that Chinese breast cancer patients with a high expression of HERV-K
      had a decreased overall survival compared with patients who had either a moderate
      or low HERV-K expression in their tumors (P = 0.049, chi(2) log rank test). In
      conclusion, the HERV-K env gene is expressed in the majority of breast cancers
      from U.S. or Chinese women but not in normal breast tissue. High expression of
      HERV-K env protein in breast cancer patients is associated with markers of
      disease progression and poor disease outcome, indicating that HERV-K env protein
      is a novel candidate prognostic marker for breast cancer.

PMID- 22593805
TI  - Improvement of Astatikopsia (Riddoch's phenomenon) after correction of vertebral
      stenoses with angioplasty.
AB  - Visual perception disorder detection may be challenging with several dozen
      different syndromes identifiable. These may range from hypofunction to
      hyperfunction in the topological as well as hodological dimensions of cerebral
      structure. We report here a case of a 61-year-old white man presented with
      dizziness and visual impairment.

PMID- 22593806
TI  - Case series of 64 slice computed tomography-computed tomographic angiography with
      3D reconstruction to diagnose symptomatic cerebral aneurysms: new standard of
      care?
AB  - CT angiography (CTA) has improved significantly over the past few years such that
      the reconstructed images of the cerebral arteries may now be equivalent to
      conventional digital angiography. The new technology of 64 slice multi-detector
      CTA can reconstruct detailed images that can reliably identify small cerebral
      aneurysms, even those <3mm. In addition, it is estimated that CT followed by
      lumbar puncture (LP) misses up to 4% of symptomatic aneurysms. We present a
      series of cases that illustrates how CT followed by CTA may be replacing CT-LP as
      the standard of care in working up patients for symptomatic cerebral aneurysms
      and the importance of performing three dimensional (3D) reconstructions. A series
      of seven cases of symptomatic cerebral aneurysms were identified that illustrate
      the sensitivity of CT-CTA versus CT-LP and the importance of 3D reconstruction in
      identifying these aneurysms. Surgical treatment was recommended for 6 of the 7
      patients with aneurysms and strict hypertension control was recommended for the
      seventh patient. Some of these patients demonstrated subarachnoid hemorrhage on
      presentation while others had negative LPs. A number of these patients with
      negative LPs were clearly symptomatic from their aneurysms. At least one of these
      cerebral aneurysms was not apparent on CTA without 3D reconstruction. 3D
      reconstruction of CTA is crucial to adequately identify cerebral aneurysms. This
      case series helps reinforce the importance of 3D reconstruction. There is some
      data to suggest that 64 slice CT-CTA may be equivalent or superior to CT-LP in
      the detection of symptomatic cerebral aneurysms.

PMID- 22593807
TI  - A randomized controlled trial of an enhanced interdisciplinary community based
      group program for people with Parkinson's disease: study rationale and protocol.
AB  - Parkinson's disease (PD) is a progressive, chronic neurodegenerative disorder for
      which there is no known cure. Physical exercise programs may be used to assist
      with the physical management of PD. Several studies have demonstrated that
      community based physical therapy programs are effective in reducing physical
      aspects of disability among people with PD. While multidisciplinary therapy
      interventions may have the potential to reduce disability and improve the quality
      of life of people with PD, there is very limited clinical trial evidence to
      support or refute the use of a community based multidisciplinary or
      interdisciplinary programs for people with PD. A two group randomized trial is
      being undertaken within a community rehabilitation service in Brisbane,
      Australia. Community dwelling adults with a diagnosis of Idiopathic Parkinson's
      disease are being recruited. Eligible participants are randomly allocated to a
      standard exercise rehabilitation group program or an intervention group which
      incorporates physical, cognitive and speech activities in a multi-tasking
      framework. Outcomes will be measured at 6-week intervals for a period of six
      months. Primary outcome measures are the Montreal Cognitive Assessment (MoCA) and
      the Timed Up and Go (TUG) cognitive test. Secondary outcomes include changes in
      health related quality of life, communication, social participation, mobility,
      strength and balance, and carer burden measures. This study will determine the
      immediate and long-term effectiveness of a unique multifocal, interdisciplinary,
      dual-tasking approach to the management of PD as compared to an exercise only
      program. We anticipate that the results of this study will have implications for
      the development of cost effective evidence based best practice for the treatment
      of people with PD living in the community.

PMID- 22593808
TI  - Thalamic alexia with agraphia.
AB  - Alexia with agraphia is defined as an acquired impairment affecting reading and
      writing ability. It can be associated with aphasia, but can also occur as an
      isolated entity. This impairment has classically been associated with a left
      angular gyrus lesion In the present study, we describe a case involving a patient
      who developed alexia with agraphia and other cognitive deficits after a thalamic
      hemorrhage. In addition, we discuss potential mechanisms of this cortical
      dysfunction syndrome caused by subcortical injury. We examined a patient who
      presented with alexia with agraphia and other cognitive deficits due to a
      hemorrhage in the left thalamus. Neuropsychological evaluation showed attention,
      executive function, arithmetic and memory impairments. In addition, language
      tests revealed severe alexia with agraphia in the absence of aphasia. Imaging
      studies disclosed an old thalamic hemorrhage involving the anterior, dorsomedial
      and pulvinar nuclei. Tractography revealed asymmetric thalamocortical radiations
      in the parietal region (left <right), and single photon emission computed
      tomography demonstrated hypoperfusion in the left thalamus that extended to the
      frontal and parietal cortices. Cortical cognitive deficits, including alexia with
      agraphia, may occur as the result of thalamic lesions. The probable mechanism is
      a diaschisis phenomenon involving thalamic tract disconnections.

PMID- 22593809
TI  - Two cases of possible neuro-Sweet disease with meningoencephalitis as the initial
      manifestation.
AB  - We report 2 cases that were considered to be neuro-Sweet disease. They initially
      manifested with meningoencephalitis and no skin lesions, and rapidly improved
      with corticosteroid therapy. In both cases, patients complained of meningitic
      symptoms such as fever and headache, and HLA-B54 and -Cw1 turned out to be
      positive over the clinical course. Cerebrospinal fluid analysis showed increased
      levels of lymphocytes and protein. In case #1, fluid-attenuated inversion
      recovery (FLAIR), magnetic resonance imaging (MRI) and diffusion-weighted images
      (DWI) showed high-intensity signals in the right dorsal medulla oblongata,
      bilateral dorsal midbrain, and left thalamus. In case #2, FLAIR and DWI showed
      high-intensity signals in the bilateral cerebellar cortex and left caudate
      nucleus. Symptoms and MRI images were markedly improved in both cases after
      corticosteroid pulse therapy. According to published diagnostic criteria, these 2
      cases were considered possible neuro-Sweet disease. These cases suggest that the
      combination of meningoencephalitis and HLA specificity is important to consider
      the possibility of neuro-Sweet disease, even without skin lesions.

PMID- 22593810
TI  - Thalamic semantic paralexia.
AB  - Alexia may be divided into different subtypes, with semantic paralexia being
      particularly rare. A 57 year old woman with a discreet left thalamic stroke and
      semantic paralexia is described. Language evalution with the Boston Diagnostic
      Aphasia Battery confirmed the semantic paralexia (deep alexia). Multimodality
      magnetic resonance imaging brain scanning excluded other cerebral lesions. A good
      recovery ensued.

PMID- 22593811
TI  - Advances in functional neuroimaging in dementias and potential pitfalls.
AB  - Neuroimaging is continuously advancing at a rapid rate and has progressed from
      excluding relatively uncommon secondary causes (stroke, tumor) to assisting with
      early diagnosis and subtype of dementia. Structural imaging has given way to
      functional, metabolic and receptor imaging.

PMID- 22593812
TI  - Total remission of severe immune thrombocytopenia after short term treatment with
      romiplostim.
AB  - Immune thrombocytopenia (ITP) in adults is an acquired chronic immune-mediated
      disorder defined by isolated thrombocytopenia. In recent years, an improved
      understanding of the pathophysiology of ITP has been achieved and it is now
      accepted that the disorder is due to increased platelet destruction and decreased
      platelet production from megakary-ocytes. Thrombopoietin (TPO)-receptor agonists
      (romiplostim and eltrombopag) are new therapeutic modalities in the treatment of
      ITP. Here we describe a case of an elderly patient with severe ITP who presented
      complete remission after short-term use of romiplostim (only 3 weekly doses).
      This finding is quite interesting as the TPO-receptor agonists are, so far,
      believed to rarely lead to off-treatment sustained remission. The common notion
      of long-term use of romiplostim could be reexamined in future studies.
      Furthermore, the short term treatment with romiplostim may reduce the cost and
      the risk of side effects.

PMID- 22593813
TI  - The OnControl bone marrow biopsy technique is superior to the standard manual
      technique for hematologists-in-training: a prospective, randomized comparison.
AB  - The purpose of this study was to compare a novel bone marrow device with the
      standard marrow needle in a prospective, randomized study in a teaching hospital
      employing hematologists-in-training. The new device, the OnControl Bone Marrow
      (OBM) Biopsy System, utilizes a battery-powered drill to insert the needle. Fifty
      four bone marrows (27 standard and 27 OBM) were performed by 11 fellows under the
      observation and supervision of 3 attending hematologists and 1 research
      technologist. The primary endpoint of the study, the mean length of the marrow
      biopsy specimens, a surrogate for marrow quality, was determined by a pathologist
      in a blinded manner. The mean length of the marrow biopsy specimens was
      significantly longer (56%) for the OBM group (15.3 mm) than for the standard bone
      marrow (SBM) group (9.8 mm), P<0.003. An objectively determined secondary
      endpoint; mean procedure time, skin-to-skin; also favored the OBM group (175 s)
      versus the SBM group (292 s), P<0.007. Several subjective secondary endpoints
      also favored the OBM group. Only minor adverse events were encountered in the OBM
      and SBM study groups. It was concluded that bone marrow procedures (BMPs)
      performed by hematologists-in-training were significantly faster and superior in
      quality when performed with the OBM compared to the SBM. These data suggest that
      the OBM may be considered a new standard of care for adult hematology patients.
      OBM also appears to be a superior method for training hematology fellows.

PMID- 22593814
TI  - Comparison of bone marrow aspirate cytology, touch imprint cytology and trephine
      biopsy for bone marrow evaluation.
AB  - Studies have compared the role of bone marrow aspirate cytology and trephine
      biopsy for diagnosing various hematological disorders but fewer studies have
      compared the relative value of imprint cytology with aspirate and trephine
      biopsy. The present study was conducted to compare the role of bone marrow
      aspirate, touch imprint and trephine biopsy to formulate an effective and rapid
      method for diagnosing wide spectrum of hematological diseases. The study included
      total 565 cases of bone marrow examination from January 2006 till May 2010. All
      the smears and sections were reviewed for morphological details and findings on
      aspirate, imprint and biopsy were compared to each other. The diagnostic accuracy
      of bone marrow aspirate was 77.5%, imprint cytology 83.7% and that of biopsy was
      of 99.2%. The study showed 78% positive correlation between aspirate and biopsy
      and 84.3% between imprint and biopsy; 93.3% cases of metastatic solid tumors were
      correctly diagnosed on imprint while only 70% cases were diagnosed on aspirate
      cytology. The study concludes that all the three preparations of aspirate,
      imprint and biopsy complement each other. The assessment of iron status by Perl's
      stain is most suitable on aspirate smears but trephine biopsy remains the gold
      standard for diagnosing granulomatous inflammation and hypoplastic/ aplastic
      anemia. Meticulously prepared imprint smears not only provide cellular
      composition of marrow but may also be helpful in defining the architecture of
      marrow especially in cases of metastatic solid tumors. Imprint cytology smears
      should be standard practice for evaluating any marrow.

PMID- 22593815
TI  - Therapy related acute myeloid leukemia with t(10:16): a rare entity.
AB  - Treatment related myelodysplastic syndrome (t-MDS) and acute myeloid leukemia (t
      AML) are well known complications after chemotherapy for various hematologic and
      non-hematologic malignancies. Alkylating agents and Topoisomerase inhibitors are
      most widely studied in this regard. There is growing concern about occurrence of
      t-MDS, t-MDS/AML and t-AML in patients of CLL treated with nucleoside analogues
      especially in combination with alkylating agents. Exact incidence and
      pathogenesis of nucleoside analogue related MDS/AML is not clear at this time. We
      hereby report a case of t-AML in a patient treated with Fludarabine,
      Cyclophosphamide and Rituximab (FCR) for CLL. The cytogenetic studies revealed a
      unique translocation t (10:16), that has been reported in very few cases of
      therapy related AML and pediatric AML.

PMID- 22593816
TI  - Haematoma caused by bone marrow aspiration and trephine biopsy.
AB  - We report a case of a bone marrow aspiration and trephine biopsy (BMATB)
      associated haematoma in an 85-years old male without any predisposing risk
      factors. Six days after BMATB, he suffered from a massive thigh and buttock
      haematoma and a fall in haematocrit. It is important to know that BMATB can have
      complications aiding early recognition and therapy.

PMID- 22593817
TI  - Significance of Bcl-2 and Bcl-6 immunostaining in B-Non Hodgkin's lymphoma.
AB  - The determination of prognosis for B-Non-Hodgkin's lymphoma (NHL) is known to be
      related to the multiple differences in tumor cell biology. Bcl-2 and Bcl-6 are
      two markers linked to germinal center B cells. Both markers are thought to have
      an effect on prognosis of mature B-cell neoplasms. Forty-four patients with
      chronic B-cell neoplasm were included; Bcl-2 and Bcl-6 expression by
      immunohistochemistry was examined. Bcl-2 protein was positive in 36.4% (16 of 44)
      of cases (62.5% of follicular lymphoma, 16.7% of mantle cell lymphoma and 30% of
      diffuse large B-cell lymphoma); the positive group implying a bad prognostic
      effect of the marker in NHL. Bcl-6 was positive in 13.6% (6 of 44) of cases
      (11.1% of mantle cell lymphoma and 40% of diffuse large B-cell lymphoma) and its
      positivity implies a better disease course. Bcl-2 and Bcl-6 can be used as
      prognostic marker in NHL.

PMID- 22593818
TI  - A case of chronic myelogenous leukemia in pregnancy characterized by a complex
      translocation t(9;22;11)(q34;q11.2;q13).
AB  - The management of chronic myelogenous leukemia during pregnancy requires
      balancing the well-being of the mother with that of the fetus. We report a case
      of a 26-year-old lady who was diagnosed with chronic myelogenous leukemia (CML)
      at 15 weeks gestation and who had an atypical chromosome t(9;22;11)
      (q34;q11.2;q13) translocation. She was observed through the remainder of the
      pregnancy and the disease remained stable; she delivered a normal boy. Treatment
      with imatinib mesylate was initiated shortly after delivery and she went into
      molecular complete remission. We discuss the course of the disease and suggest
      guidelines for managing pregnancy with respect to the currently available agents
      imatinib, dasatinib and nilotinib.

PMID- 22593819
TI  - Clinical significance of P53 and Bcl-2 in acute myeloid leukemia patients of
      Eastern India.
AB  - The frequency of p53 and Bcl-2 protein expression in 100 newly diagnosed and 10
      relapsed acute myeloid leukemia (AML) patients was analyzed by
      immunocytochemistry (ICC). The Kaplan-Meier method was used for univariate and
      multivariate statistical analysis to assess the relationship between p53, Bcl-2
      and clinico-hematologic feature with respect to overall survival (OS) using SPSS
      statistical software. No statistical significance was found in univariate
      analysis (P=0.60). However, when the subgroups of patients (+1, +2, +3 and +4)
      were compared, expression of p53 and Bcl-2 protein (1-10%, 11-30%, 31-50% and
      >50%) was statistically significant (P<0.05). However, in multivariate analysis,
      p53, immunopositivity was independently associated with a shorter overall
      survival (OS) (P=0.038) while Bcl-2 immunopositivity was associated with longer
      overall survival (OS) (P=0.002). Our finding shows that p53 and Bcl-2 protein
      overexpression is a strong indicator of response to chemotherapy and overall
      survival. This study reports for the first time AML in patients from Eastern
      India.

PMID- 22593820
TI  - Tyrosine kinase inhibitors induced immune thrombocytopenia in chronic myeloid
      leukemia?
AB  - The outcome and quality of life of chronic myeloid leukemia (CML) patients has
      remarkably changed with the treatment of tyrosine kinase inhibitors (TKIs).
      Currently, hematopoietic stem cell transplantation (HSCT) is considered mainly as
      a third line salvage therapy in cases of TKIs resistance or intolerance. Here we
      describe a patient with chronic phase CML who developed both resistance and late
      occurrence of s severe thrombo-cytopenia on first and second generation TKIs and
      eventually underwent HSCT. Although the mechanism of the myelosuppression is not
      fully understood, we showed for the first time the development of dose dependent
      platelet antibodies in the presence of TKIs, suggesting the possibility of TKIs
      induced thrombocytopenia. Our case emphasizes that late development of severe
      myelosuppression during imatinib treatment is probably an important indication
      for consideration of early HSCT.

PMID- 22593821
TI  - A rare case of coinheritance of Hemoglobin H disease and sickle cell trait
      combined with severe iron deficiency.
AB  - We present a case of a 40-year-old female from Turkey, who was referred to our
      outpatient clinic for an undetermined thalassemia and sickle cell trait. At first
      consultation hemoglobin was decreased (71 g/L) with microcytosis (MCV 55.1 fL),
      and hypochromia (MCHC 239 g/L). The patient had severe iron deficiency. Brilliant
      cresyl blue staining showed >50% of the erythrocytes with typical Hemoglobin H
      (HbH) inclusions. High-performance liquid chromatography (HPLC) revealed normal
      levels of HbA(2) and Hemoglobin F (HbF), and additionally a hemoglobin S (19%).
      Molecular diagnostics revealed the mutations alpha2 IVS-I donor site -5nt and a -
      MED II deletion in the alpha gene complex and confirmed the heterozygote
      mutation of the beta-gene at codon 6 (HBB:c.20A>T; HbS). In conclusion, we
      present an extremely rare combination of HbH disease and sickle cell trait. This
      combination may explain the mild form of the HbH disease, with moderate anemia,
      splenomegaly but iron deficiency, rather than iron overload, as usually observed
      in HbH disease.

PMID- 22593822
TI  - Vacuolar status and water relations in embryonic axes of recalcitrant Aesculus
      hippocastanum seeds during stratification and early germination.
AB  - BACKGROUNDS AND AIMS: In tropical recalcitrant seeds, their rapid transition from
      shedding to germination at high hydration level is of physiological interest but
      difficult to study because of the time constraint. In recalcitrant horse chestnut
      seeds produced in central Russia, this transition is much longer and extends
      through dormancy and dormancy release. This extended time period permits studies
      of the water relations in embryonic axes during the long recalcitrant period in
      terms of vacuolar status and water transport. METHODOLOGY: Horse chestnut
      (Aesculus hippocastanum) seeds sampled in Moscow were stratified in cold wet sand
      for 4 months. Vacuole presence and development in embryonic axes were examined by
      vital staining, light and electron microscopy. Aquaporins and vacuolar H(+)
      ATPase were identified immunochemically. Water channel operation was tested by
      water inflow rate. Vacuolar acid invertase was estimated in terms of activity and
      electrophoretic properties. PRINCIPAL RESULTS: Throughout the long recalcitrant
      period after seed shedding, cells of embryonic axes maintained active vacuoles
      and a high water content. Preservation of enzyme machinery in vacuoles was
      evident from retention of invertase activity, substrate specificity, molecular
      mass and subunit composition. Plasmalemma and tonoplast aquaporins and the E
      subunit of vacuolar H(+)-ATPase were also present. In non-dormant seeds prior to
      growth initiation, vacuoles enlarged at first in hypocotyls, and then in
      radicles, with their biogenesis being similar. Vacuolation was accompanied by
      increasing invertase activity, leading to sugar accumulation and active osmotic
      functioning. After growth initiation, vacuole enlargement was favoured by
      enhanced water inflow through water channels formed by aquaporins. CONCLUSIONS:
      Maintenance of high water content and desiccation sensitivity, as well as
      preservation of active vacuoles in embryonic axes after shedding, can be
      considered a specific feature of recalcitrant seeds, overlooked when studying
      tropical recalcitrants due to the short duration. The retained physiological
      activity of vacuoles allows them to function rapidly as dormancy is lost and when
      external conditions permit. Cell vacuolation precedes cell elongation in both
      hypocotyl and radicle, and provides impetus for rapid germination.

PMID- 22593824
TI  - Comparison of different methods for the calculation of the microvascular flow
      index.
AB  - The microvascular flow index (MFI) is commonly used to semiquantitatively
      characterize the velocity of microcirculatory perfusion as absent (0),
      intermittent (1), sluggish (2), or normal (3). There are three approaches to
      compute MFI: (1) the average of the predominant flow in each of the four
      quadrants (MFI(by quadrants)), (2) the direct assessment during the bedside video
      acquisition (MFI(point of care)), and (3) the mean value of the MFIs determined
      in each individual vessel (MFI(vessel by vessel)). We hypothesized that the
      agreement between the MFIs is poor and that the MFI(vessel by vessel) better
      reflects the microvascular perfusion. For this purpose, we analyzed 100 videos
      from septic patients. In 25 of them, red blood cell (RBC) velocity was also
      measured. There were wide 95% limits of agreement between MFI(by quadrants) and
      MFI(point of care) (1.46), between MFI(by quadrants) and MFI(vessel by vessel)
      (2.85), and between MFI(by point of care) and MFI(vessel by vessel) (2.56). The
      MFIs significantly correlated with the RBC velocity and with the fraction of
      perfused small vessels, but MFI(vessel by vessel) showed the best R(2). Although
      the different methods for the calculation of MFI reflect microvascular perfusion,
      they are not interchangeable and MFI(vessel by vessel) might be better.

PMID- 22593825
TI  - Optimization of Cannula Visibility during Ultrasound-Guided Subclavian Vein
      Catheterization, via a Longitudinal Approach, by Implementing Echogenic
      Technology.
AB  - Objective. One limitation of ultrasound-guided vascular access is the technical
      challenge of visualizing the cannula during insertion into the vessel. We
      hypothesized that the use of an echogenic vascular cannula (EC) would improve
      visualization when compared with a nonechogenic vascular cannula (NEC) during
      real-time ultrasound-guided subclavian vein (SCV) cannulation in the ICU.
      Material and Methods. Eighty mechanically ventilated patients were prospectively
      enrolled in a randomized study that was conducted in a medical-surgical ICU.
      Forty patients underwent EC and 40 patients were randomized to NEC. The procedure
      was ultrasound-guided SCV cannulation via the infraclavicular approach on the
      longitudinal axis. Results. The EC group exhibited increased cannula visibility
      as compared to the NEC group (92%+/-3% versus 85 +/- 7%, resp., P < 0.01). There
      was strong agreement between the procedure operators and independent observers (k
      = 0.9, 95% confidence intervals assessed by bootstrap analysis = 0.87 to 0.93; P
      < 0.01). Access time (12.1 s +/- 6.5 versus 18.9 s +/- 10.9) and the perceived
      technical difficulty of the ultrasound method (4.5 +/- 1.5 versus 7.5 +/- 1.5)
      were both decreased in the EC group compared to the NEC group (P < 0.05).
      Conclusions. Echogenic technology significantly improved cannula visibility and
      decreased access time and technical complexity optimizing thus real-time
      ultrasound-guided SCV cannulation via a longitudinal approach.

PMID- 22593823
TI  - Prevalence of Drug Resistance and Associated Mutations in a Population of HIV
      1(+) Puerto Ricans: 2006-2010.
AB  - This is a continuation of our efforts to maintain a record of the evolution of
      HIV-1 infection in Puerto Rico by monitoring the expression levels of
      antiretroviral drug-resistance-associated mutations. Samples from 2,500 patients
      from 2006-2010 were analyzed using the TruGene HIV-1 genotyping kit and the
      OpenGene DNA sequencing system. Results show that 58.8% of males and 65.3% of
      females had HIV-1 with resistance to at least one medication. The average number
      of HIV mutations was 6.0 in males and 6.1 in females. Statistically significant
      differences between men and women were recorded in the levels of HIV-1 expressed
      mutations and antiretroviral drug resistance. The most prevalent antiretroviral
      medication resistance shifted from zalcitabine to nevirapine and efavirenz in the
      five-year period. M184V and L63P were the dominant mutations for the reverse
      transcriptase and the protease genes, respectively, but an increase in the
      incidence of minority mutations was observed.

PMID- 22593826
TI  - Glycosaminoglycans metabolism.

PMID- 22593828
TI  - HIV/AIDS, tuberculosis, and malaria in pregnancy.

PMID- 22593829
TI  - Interactions between Bile Acids and Nuclear Receptors and Their Effects on Lipid
      Metabolism and Liver Diseases.

PMID- 22593831
TI  - Benign osteoblastoma involving maxilla: a case report and review of the
      literature.
AB  - Background. Osteoblastoma is a rare benign tumor. This tumor is characterized by
      osteoid and bone formation with the presence of numerous osteoblasts. The lesion
      is more frequently seen in long bones and rarely involves maxilla and mandible.
      Due to its clinical and histological similarity with other bone tumors such as
      osteoid osteoma and fibro-osseous lesions, osteoblastoma presents a diagnostic
      dilemma. Case Report. Very few cases of osteoblastomas involving maxillofacial
      region have been reported in the literature. This case report involves
      osteoblastoma involving right maxilla in an 18-year-old male patient. Following
      detailed clinical examination, radiological interpretation, and histopathological
      diagnosis, surgical excision was performed. The patient was followed up for a
      period of 3 years and was disease free. Summary and Conclusion. Benign
      osteoblastoma involving jaw bones is a rare tumor. There is a close resemblance
      of this tumor with other lesions such as fibro-osseous lesions and odontogenic
      tumors and thus faces a diagnostic challenge. Surgical excision with a long-term
      follow-up gives good prognosis to this lesion-Benign Osteoblastoma.

PMID- 22593830
TI  - Stem cell therapy for degenerative disc disease.
AB  - Low back pain is widely recognized as one of the most prevalent pathologies in
      the developed world. In the United States, low back pain is the most common
      health problem for adults under the age of 50, resulting in significant societal
      and personal costs. While the causes of low back pain are myriad, it has been
      significantly associated with intervertebral disc (IVD) degeneration. Current
      first-line therapies for IVD degeneration such as physical therapy and spinal
      fusion address symptoms, but do not treat the underlying degeneration. The use of
      tissue engineering to treat IVD degeneration provides an opportunity to correct
      the pathological process. Novel techniques are currently being investigated and
      have shown mixed results. One major avenue of investigation has been stem cell
      injections. Mesenchymal stem cells (MSCs) have shown promise in small animal
      models, but results in larger vertebrates have been mixed.

PMID- 22593832
TI  - Fecal Bacteriotherapy: A Case Report in an Immunosuppressed Patient with
      Ulcerative Colitis and Recurrent  Clostridium difficile Infection.
AB  - We report a case of ulcerative colitis (UC) and recurrent Clostridium difficile
      infection (CDI) where the patient was on immunomodulatory therapy and had
      successful CDI eradication after fecal transplantation. This is the first case
      report in the literature documenting successful C. difficile eradication in an
      immunosuppressed patient. We feel that fecal transplantation should be studied as
      a treatment option in these patients.

PMID- 22593833
TI  - Comparison of provision of stroke care in younger and older patients: findings
      from the South london stroke register.
AB  - Background. Evidence-based stroke care should be available to all patients.
      However, evidence exists of inequalities according to age. This study compared
      access to care for younger adults to that for over 65s. Methods. Using population
      based data from 4229 patients with first-ever stroke between 1995 and 2010,
      associations between age and 21 care indicators were investigated using
      multivariable logistic regression. Results. Age was not associated with stroke
      unit admission for ischaemic stroke (P = 0.666). Younger PICH patients were least
      likely to be admitted to stroke units (P = 0.001), instead treated on
      neurosurgical or ICU wards. Younger age was also associated with admission to
      neurosurgery or ICU after SAH (P = 0.006), increased occupational or
      physiotherapy at 1 year (P = 0.043), and contact with a GP 3 months after stroke
      (P < 0.001). Conclusion. Younger patients have equal or greater access to
      evidence-based care. However, there is a need to ensure that services meet the
      needs of this group.

PMID- 22593834
TI  - Motor imagery experiences and use: asking patients after stroke where, when,
      what, why, and how they use imagery: a qualitative investigation.
AB  - Background. A framework on where, when, what, why, and how to use imagery from
      sports psychology was explored whether it can be applied in patients after stroke
      in their chronic stage. Methods. Eleven patients (ages 31-85, 3 females, 1.3-6.4
      years after stroke) were interviewed. Semistructured interviews were conducted
      before and after a two-week MI intervention period with six MI sessions.
      Information was obtained regarding experiences and knowledge of MI, and the
      evaluation of an MI practical example. The coding scheme was based on the
      framework and a hierarchical categorisation. Results. Information regarding
      domains where, when, what, why, and how to use imagery was addressed. Patients
      imagined themselves as healthy individuals, did not focus on surroundings during
      MI practice,and reported to use positive imagery only. After MI training,
      patients became more flexible regarding their location and position during MI
      practice. Conclusions. MI became an automatic process, and patients did not need
      specific concentration and quietness as mentioned in the first interview.
      Patients recommended daily MI training and began to transfer MI to practice
      movements that were affected by the stroke. In contrast to sports, patients did
      not talk about how MI was triggered rather than how MI was designed.

PMID- 22593827
TI  - Mitochondria: redox metabolism and dysfunction.
AB  - Mitochondria are the main intracellular location for fuel generation; however,
      they are not just power plants but involved in a range of other intracellular
      functions including regulation of redox homeostasis and cell fate. Dysfunction of
      mitochondria will result in oxidative stress which is one of the underlying
      causal factors for a variety of diseases including neurodegenerative diseases,
      diabetes, cardiovascular diseases, and cancer. In this paper, generation of
      reactive oxygen/nitrogen species (ROS/RNS) in the mitochondria, redox regulatory
      roles of certain mitochondrial proteins, and the impact on cell fate will be
      discussed. The current state of our understanding in mitochondrial dysfunction in
      pathological states and how we could target them for therapeutic purpose will
      also be briefly reviewed.

PMID- 22593837
TI  - Proceedings of the First Symposium on Innovative Polymers for Controlled
      Delivery, September 14-17, 2010, Suzhou, China.

PMID- 22593835
TI  - ENGAGE: Guided Activity-Based Gaming in Neurorehabilitation after Stroke: A Pilot
      Study.
AB  - Introduction. Stroke is a leading cause of disability in healthy adults. The
      purpose of this pilot study was to assess the feasibility and outcomes of a novel
      video gaming repetitive practice paradigm, (ENGAGE) enhanced neurorehabilitation:
      guided activity-based gaming exercise. Methods. Sixteen individuals at least
      three months after stroke served as participants. All participants received
      concurrent outpatient therapy or took part in a stroke exercise class and
      completed at least 500 minutes of gaming. Primary baseline and posttest outcome
      measures included the Wolf motor function test (WMFT) and the Fugl-Meyer
      assessment (FMA). ENGAGE uses a game selection algorithm providing focused,
      graded activity-based repetitive practice that is highly individualized and
      directed. The Wilcoxon signed ranks test was used to determine statistical
      significance. Results. There were improvements in the WMFT (P = 0.003) and the
      FMA (P = 0.002) that exceeded established values of minimal clinically important
      difference. Conclusions. ENGAGE was feasible and an effective adjunct to
      concurrent therapy after stroke.

PMID- 22593836
TI  - Proceedings of the 14th International Amine Oxidase Workshop, July 18, 2010,
      Edmonton, Alberta, Canada.

PMID- 22593838
TI  - Proceedings of the 6th International Hematologic Malignancies Conference, October
      13-16, 2010, Houston, Texas.

PMID- 22593839
TI  - Incidents, incidence and golden eggs.

PMID- 22593840
TI  - Patient-centric? Third-party payers interfere.

PMID- 22593841
TI  - Patient-centric? Third-party payers interfere.

PMID- 22593842
TI  - Seeing patients for less  should count as charity care.

PMID- 22593843
TI  - We need to hone the media image  of family physicians.

PMID- 22593844
TI  - A variety of opportunities for immune interactions during trophoblast development
      and invasion.
AB  - During human implantation and placentation, the direct cell to cell contact of
      fetal and maternal tissues gives room for a variety of immune interactions.
      Especially, the invasion of a subset of fetal trophoblast cells, called
      extravillous trophoblast, generate a very close interplay between the two
      individuals, enabling the attachment of the placenta to the uterine wall and the
      transformation of maternal spiral arteries to facilitate adequate nutrition of
      the fetus. During pregnancy, maternal and fetal factors closely interact to
      maintain pregnancy and smooth the process of delivery. At each and every stage
      and site, immunological interactions take place, including attachment of the
      blastocyst, development and invasion of trophoblast, and flow of maternal plasma
      and blood through the intervillous space of the placenta. Control mechanisms
      tightly regulate these interactions helping to evade fetal rejection by the
      mother. In this review, we highlight the morphological sites of development and
      feto-maternal interaction to help immunological interested scientists and
      clinicians to develop hypotheses on the feto-maternal immunological network
      during pregnancy.

PMID- 22593847
TI  - Circulating mitotic figures in CMV-associated hydrops fetalis.

PMID- 22593848
TI  - Clarifying benefit packages takes time, insurers insist.

PMID- 22593845
TI  - Blood transfusion utilization and recipient survival at Hospital das Clinicas in
      Sao Paulo, Brazil.
AB  - BACKGROUND: The characteristics of blood recipients including diagnoses
      associated with transfusion and posttransfusion survival are unreported in
      Brazil. The goals of this analysis were: 1) to describe blood utilization
      according to clinical diagnoses and patient characteristics and 2) to determine
      the factors associated with survival of blood recipients. STUDY DESIGN AND
      METHODS: A retrospective cross-sectional analysis was conducted on all inpatients
      in 2004. Data came from three sources: The first two files consist of data about
      patient characteristics, clinical diagnosis, and transfusion. Analyses comparing
      transfused and nontransfused patients were conducted. The third file was used to
      determine survival recipients up to 3 years after transfusion. Logistic
      regression was conducted among transfused patients to examine characteristics
      associated with survival. RESULTS: In 2004, a total of 30,779 patients were
      admitted, with 3835 (12.4%) transfused. These patients had 10,479 transfusions
      episodes, consisting of 39,561 transfused components: 16,748 (42%) red blood
      cells, 15,828 (40%) platelets (PLTs), and 6190 (16%) plasma. The median number of
      components transfused was three (range, 1-656) per patient admission. Mortality
      during hospitalization was different for patients whose admissions included
      transfusion or not (24% vs. 4%). After 1 year, 56% of transfusion recipients were
      alive. The multivariable model of factors associated with mortality after
      transfusion showed that the most significant factors in descending order were
      hospital ward, increasing age, increasing number of components transfused, and
      type of components received. CONCLUSION: Ward and transfusion are markers of
      underlying medical conditions and are associated with the probability of
      survival. PLT transfusions are common and likely reflect the types of patients
      treated. This comprehensive blood utilization study, the first of its kind in
      Brazil, can help in developing transfusion policy analyses in South America.

PMID- 22593849
TI  - Trisomy 21 DNA test (MaterniT21) for detecting Down syndrome in the first
      trimester.

PMID- 22593850
TI  - Health information officers a hot commodity.

PMID- 22593851
TI  - Virtual vs. actual networks.

PMID- 22593852
TI  - CEO contends that eliminating financial risk allows Medicaid plans to focus on
      management.

PMID- 22593853
TI  - Herzlinger predicts ACOs, PCMHs will fail.

PMID- 22593855
TI  - Wendell Potter: Insurers will be radically different.

PMID- 22593854
TI  - AHIP's Karen Ignagni: Health insurers will continue to innovate.

PMID- 22593856
TI  - Payers, providers weigh value of some costly biologics.

PMID- 22593857
TI  - Insurers skeptical of usefulness of companion diagnostics.

PMID- 22593858
TI  - NPs & PAs--top hiring priority for medical groups.

PMID- 22593974
TI  - Restructuring health policy networks: A French policy style?

PMID- 22593975
TI  - Franco-German bilateralism and agricultural politics in the European Union: the
      neglected level.

PMID- 22593976
TI  - Moral strength through material defeat? The consequences of 1898 for Spanish
      military culture.

PMID- 22593977
TI  - The last phase of the gentleman's war: British handling of German prisoners of
      war on board HMT "Pasteur," March 1942.

PMID- 22593978
TI  - "The womb of a woman belongs to the motherland": press images of Israeli women in
      wartime, 1967-1973.

PMID- 22593979
TI  - Perceptions of death and the Korean War.

PMID- 22593980
TI  - "Sort of part of the women's movement. But different": mothers' organisations and
      Australian feminism.

PMID- 22593981
TI  - A private eye on feminist agency: reflections on self-documentation, biography,
      and political consciousness.

PMID- 22593982
TI  - Cosmetic surgery in a different voice: the case of Madame Noel.

PMID- 22593983
TI  - Feminism in Malaysia: a historical and present perspective of women's struggles
      in Malaysia.

PMID- 22593984
TI  - [Address by rector of the Pomeranian Medical University in Szczecin inaugurating
      the academic year of 2010/2011].

PMID- 22593985
TI  - [Autonomic disorders in Parkinson's disease].
AB  - INTRODUCTION: Autonomic disorders (AD) are one of non-motor symptoms in
      Parkinson's disease (PD). The aim of this study was to assess the frequency of AD
      in PD patients and their relationship with age, gender, disease duration,
      treatment duration, L-dopa dose, and disease severity. MATERIAL AND METHODS: 101
      patients with PD were recruited. Anamnesis was recorded with a focus on
      orthostatic hypotension, sialorrhea, dysphagia, nausea/vomiting, loss of
      appetite, weight loss, constipation, nycturia, urgency, pollakiuria, difficulties
      in starting miction, urinary incontinence, erectile dysfunction, sweating,
      heat/cold intolerance, and seborrhea. Mann-Whitney test and Pearson's chi2 test
      were used for statistical analysis. RESULTS: The study group comprised 53 men and
      48 women, aged 42-84 years, mean age 67.69 years. The disease duration was 1-25
      years, mean 6.5 years, L-dopa treatment duration was 1-20 years, mean 6.04 years,
      L-dopa dose was 300-2000 mg/24 h, mean 636 mg/24 h, UPDRS score was 8-103 pts,
      mean 36.38 pts. Orthostatic hypotension was found in approximately 16% of the
      patients. As regards gastrointestinal disorders, more than 40% of patients
      suffered from constipation, more than 32% from dysphagia, almost 28% from
      sialorrhea, approximately 11% from loss of appetite, 6.93% from weight loss, 2%
      from nausea/vomiting. The distribution of urogenital disorders was as follows:
      almost 85% of patients had erectile dysfunction, almost 57% nycturia, 24.78%
      urinary incontinence, approximately 22% pollakiuria, and almost 12% urgency and
      difficulties with erection. One-third of PD patients suffered from seborrhea,
      16.83% from sweating, and almost 9% from heat/cold intolerance. CONCLUSIONS: The
      most frequent AD in PD were: erectile dysfunction, nycturia, constipation,
      dysphagia, and seborrhea. Age correlated with orthostatic hypotension,
      constipation, and urinary incontinence, and with erectile dysfunction in men.
      Women were predisposed to weight loss and sweating. Men were predisposed to
      difficulties in starting miction. Disease duration correlated with constipation,
      nycturia, and urinary incontinence; L-dopa treatment duration correlated with
      nausea/vomiting and constipation; L-dopa dose correlated with nausea/vomiting,
      constipation, urgency, and heat/cold intolerance; disease stage correlated with
      sialorrhea, constipation, sweating, and heat/cold intolerance.

PMID- 22593986
TI  - [Cases of congenital eye malformations in children].
AB  - PURPOSE: The aim of this work was to present a clinical picture of congenital
      defects in the anterior and posterior segment of the eye and coexisting systemic
      developmental anomalies in a group of children during the infantile period.
      MATERIAL AND METHODS: We performed a retrospective analysis in a group of 1507
      infants seen at our outpatient ophthalmology clinic in 2006-2010. Attention was
      focused on case histories of nine children (0.6%) with congenital defects of the
      eye. A routine ophthalmologic examination was done and photographs of the
      anterior and posterior segment of the eye were archived with the Ret - Cam II
      apparatus. Maternal risk factors during pregnancy and the perinatal period were
      analyzed, as well as genetic, familial, infectious, traumatic, metabolic, and
      toxic factors, and drugs which could have contributed to the pathology of the
      organ of vision. Additionally, congenital polydysplasia was confirmed using
      ultrasonography, radiography, and imaging techniques (USG, X-ray, MRI). RESULTS:
      Congenital anomalies of the anterior and posterior segment of the eye were
      identified in the study group. Abnomalities of the anterior segment of the eye in
      four infants were in the form of congenital corneal anomalies (keratopathy,
      microcornea, sclerocornea, congenital mesenchymal dysgenesis), coloboma of the
      iris, and aniridia. Additionally, ectopic pupil, congenital cataract, aplasia of
      the lacrimal point, and palpebral coloboma were observed. Developmental anomalies
      of the posterior segment of the eye in the form of persistent hyperplastic
      primary vitreous body or primary fetal vasculature syndrome (PHVB or PFVS),
      choroid coloboma, coloboma of the optic nerve, and optic disc fovea were
      recognized in eight children. Anomalies of the anterior and posterior segment of
      the eye were observed in three children and were associated with microphthalmia,
      nystagmus, and strabismus. Moreover, systemic anomalies coexisting with
      ophthalmologic defects were confirmed in 6 children. They were seen in the heart
      (patent ductus arteriosus (PDA), patent foramen ovale (Pfo), atrial septal defect
      (ASD), nervous system (aplasia of the corpus callosum, hydrocephalus),
      osteoarticular system (talipes equinovarus, bifurcate rib, butterfly vertebra,
      dysmorphic splanchnocranium, contracture of the fingers), genitourinary system
      (cryptorchism, Wilms' tumor, vesicoureteral reflux grade IV), auditory organ
      (microtia, aplasia of the external auditory meatus, tympanic cavity, and internal
      ear), and skin (telangiectasia, syndactyly, appendages, and vegetations). Genetic
      tests revealed one case of an abnormal karyotype (49, XXXXX). Infections,
      metabolic disorders, and intoxications were excluded as the background for the
      anomalies. CONCLUSIONS: The finding of a congenital eye anomaly should be
      followed by a search for other systemic anomalies. Developmental anomalies of the
      eye and other organs will require a multidisciplinary approach to treatment and
      care.

PMID- 22593987
TI  - [Strategy of physiotherapy in dysphagia associated with spinal muscular atrophy
      type Ib: Case study].
AB  - INTRODUCTION: Neuromuscular diseases progress to pathologic conditions which
      reveal structural or functional lesions of the elements forming the motor unit of
      the body. Typical clinical symptoms include muscle weakness, muscle flaccidity,
      pareses, and partial or total loss of reflexes. Excessive intensity of these
      symptoms leads i.a. to motor dysfunctions and ultimately to problems with
      physical development of children and youth. Treatment of such conditions is based
      on physiotherapy. The aim of this article is to expose the growing problem of
      dysphagia in patients with neuromuscular diseases and to systematize therapeutic
      activities during the process of rehabilitation. MATERIAL AND METHODS: We present
      the case of a 25-year-old male with SMA Ib diagnosed at birth, with full-blown
      symptoms of mechanical and oropharyngeal dysphagia. The patient complained of jaw
      rigidity, reduced oral aperture, difficulties in moving food in the oral cavity,
      loss of masticatory force, weakness and quickly progressing fatigue of jaw
      muscles during chewing, and problems with swallowing. Prior to the
      physiotherapeutic test, we performed a qualitative and quantitative assessment of
      temporomandibular joint (TMJ) mobility. Quantitative assessment of movement range
      was done in accordance with principles for functional examination of the
      masticatory organ in dentistry with the use of a millimeter ruler. We also
      recorded the subjective assessment by the patient of eating and swallowing.
      Assessment was done at the start and end of therapy (after 8 weeks). The patient
      underwent an 8-week course of therapy which consisted of stretching of cervical
      muscles according to Anderson, massage of soft tissues in the TMJ region,
      acupressure of the attachment of the masseter muscle (on the zygomatic bone),
      postisometric relaxation ofmasseter muscles (in the direction of abduction),
      active TMJ movements, active tongue exercises, and swallowing maneuvers.
      Rehabilitation was performed according to the sequence above during 20-minute
      sessions three times per week. RESULTS: We observed objective and subjective
      improvement after our physiotherapy of the patient. TMJ mobility increased and
      the patient reported subjective improvement in the quality of life manifested
      with greater comfort during eating, moving, chewing, and swallowing food.
      CONCLUSIONS: Therapy ofdysphagia in SMA Ib patients should be included as early
      as possible in the rehabilitation program in anticipation of problems with food
      ingestion. Therapy of dysphagia should be comprehensive, i.e. should not be
      limited to exercises stimulating TMJ mobility but should also address tongue
      movements and therapy of soft tissues. Therapy needs to be continuous and
      systematic regardless of the severity of dysphagia. It is particularly important
      to start dysphagia prevention measures in children with neuromuscular disorders
      by including exercises of the masticatory organ in the rehabilitation program.

PMID- 22593988
TI  - Psychologic aspects of Dupuytren's disease: a new scale of subjective well-being
      of patients.
AB  - INTRODUCTION: Dupuytren's disease usually appears in middle-age patients and is
      more prevalent in men than women (2-10 times less often than in men). Dupuytren's
      disease may accompany diabetes, smoking, alcoholism, HIV, and epilepsy. There is
      no cure for this disease. The disease causes a remarkable worsening of the
      quality of life resulting mainly from two factors: reduced physical performance
      or disability, and disfigurement. MATERIAL AND METHODS: We studied 38 patients
      suffering from Dupuytrens's disease. The study was done in 2007-2008 at the
      Second Department of Surgery of the Jagiellonian University. We used the
      Dupuytrens disease scale of subjective well being of patients (DDSP)
      questionnaire covering four areas of the quality of life. RESULTS: Blue-collar
      workers experienced more severe problems at work than white-collar workers.
      CONCLUSION: There were no differences between location of the disease in left-
      and right-handed patients.

PMID- 22593989
TI  - [Antimalarial drugs in contemporary dermatologic therapy].
AB  - Antimalarial drugs--chloroquine, hydroxychloroquine and quinacrine, initially
      devised for the treatment of malaria, have been used in the therapy of diverse
      skin diseases, including lupus erythematosus, dermatomyositis, porphyria cutanea
      tarda, and sarcoidosis. The mechanism of action of these drugs involves
      stabilization of lysosomal enzymes, inhibition of antigen-presenting cells and T
      lymphocyte stimulation, blocking of the pro-inflammatory cytokine cascade and
      endosomal toll-like receptor signaling. The understanding of potential mechanisms
      of action of antimalarials may extend their use to new areas in dermatology. This
      work describes the pharmacologic properties of antimalarial drugs and indications
      for their use in clinical practice. Moreover, the most important limitations of
      therapy with antimalarials and their adverse side effects are discussed.

PMID- 22593990
TI  - [Study of depressiveness with Beck Depression Inventory in patients with cardiac
      arrhythmias].
AB  - INTRODUCTION: Atrial fibrillation belongs to the group of supraventricular
      arrhythmias. The episode begins with anxiety about the loss of health or life.
      Anxiety is accompanied by depressive disorders. The aim of this work was to study
      the intensity of depression in patients with atrial fibrillation. MATERIAL AND
      METHODS: We used Beck Depression Inventory in 52 patients with atrial
      fibrillation hospitalized at the Department of Internal Medicine of the Poviat
      Hospital in Bialogard. Correlations between the intensity of depression and age,
      gender, and education level were determined. RESULTS: The intensity of depression
      depended on age, gender, and education level. Mild depression was more common in
      women, moderate in men, and was very severe in 2 women. Patients between the age
      of 61 and 80 years and with incomplete primary and vocational education presented
      with all forms of depression. CONCLUSIONS: The intensity of depression correlates
      with episodes of atrial fibrillation and depends on such factors as age, gender,
      and education level (p < 0.05). Effective therapy of atrial fibrillation may help
      reduce the intensity of depression.

PMID- 22593991
TI  - Effectiveness of strontium-89 palliative therapy in patients with painful bone
      metastases.
AB  - INTRODUCTION: Bone metastases are observed in 30-70% of patients with cancer.
      Painful bone metastases require regular control and treatment. Systemic
      palliative radiotherapy using beta-emitting radionuclides is an alternative
      method to analgesics and external beam radiotherapy. The aim of the study was to
      establish the efficacy and risk of side effects of radionuclide therapy in
      patients with bone metastases. MATERIAL AND METHODS: Strontium-89 (Sr-89) therapy
      was performed in 49 patients, 14 women and 35 men, aged 42-82 (mean 62) years
      with bone metastases confirmed by MDP-Tc99m whole body scan. The primary tumour
      was prostate cancer in 28 patients, breast cancer in 14, bladder cancer in 2,
      lung cancer in 2, gastric cancer in 2, and renal cancer in 1 patient. Intravenous
      injection of 150 MBq of Sr-89 was given and patients were observed for at least 3
      months. Blood count, intensity of pain, drugs intake, life activity, and duration
      of effect were assigned 0-3 points. The overall response index was very good when
      the points totalled 10-12, good - 7-9, satisfactory - 4-6, poor - 2-3 and no
      response 0-1 points. Haemotoxicity was evaluated according to the Common Toxicity
      Criteria of the World Health Organisation (WHO). RESULTS: We found a very good
      response in 10 (20%) patients, good in 20 (41%), satisfactory in 8 (16%), poor in
      2 (4%), and no response in 9 (19%) patients. Transient haemotoxicity of the Sr-89
      therapy was observed in 39 (80%) patients. The mean decrease in platelets and
      leukocytes was 33-35%, but the haemoglobin concentration was reduced by only 15%
      in comparison to baseline values. The majority of patients did not require any
      treatment for haematologic side effects. Hospitalization was necessary in only 2
      patients with grade 4 CTC WHO. CONCLUSION: Palliative radionuclide treatment of
      painful bone metastases with Strontium-89 in various primary tumours is in most
      cases an effective therapy with limited haemotoxicity.

PMID- 22593992
TI  - Thyroid fine-needle aspiration biopsy: which lesions should be biopsied before
      131I therapy?
AB  - INTRODUCTION: Suspicion of a neoplasm is one of the contraindications to
      radioiodine therapy in benign thyroid disease. The aim of this study was to
      present an optimal qualification scheme for fine-needle aspiration biopsy (FNAB)
      to rule out neoplastic lesions prior to radioiodine therapy. MATERIAL AND
      METHODS: 4207 patients with hyperthyroidism were referred for 131I therapy in
      2000-2006. Prior to 131I therapy, all patients underwent thyroid function
      assessment, radioiodine uptake, scintigraphy, and ultrasound. Fine-needle
      aspiration biopsy with cytology was done in 578 (13.7%) patients. Therapeutic
      radioiodine was administered to 3564 (84.7%) patients. RESULTS: Malignancy was
      confirmed or suspected in 12 female patients (0.28% of all patients and 2.07% of
      patients who underwent FNAB). Prior to the study, cytology was done in only one
      patient. The diameter of the lesions was 6-28 mm. Cytology confirmed papillary
      carcinoma in 4 patients, follicular tumour in 6, and Hurthle's cell tumour in 1.
      There were indications for histopathology in one patient due to the presence of
      atypical cells. The primary diagnosis was toxic nodular goitre in 8 patients and
      Graves' disease in 4 patients. One of the patients with follicular tumour was
      referred for radioiodine therapy due to intolerance to thyrostatic drugs, elderly
      age, and comorbidities. CONCLUSIONS: 1. Thyroid scintigraphy prior to therapy is
      important for the choice of the site of FNAB. 2. Thyroid lesions in patients with
      nodular Graves' disease must be carefully investigated to exclude malignancy. 3.
      Preselection of patients for treatment of benign thyroid disease should be
      followed by cytology of the lesions at the Department of Nuclear Medicine.

PMID- 22593993
TI  - Intracerebral metastasis of glioblastoma multiforme. Case report and literature
      review.
AB  - Glioblastoma multiforme is the most common primary malignant brain tumor in
      adults. It's characterized by a high malignancy and rapid, frequent tendency to
      local recurrence. Distant metastases disseminated in the brain compared to the
      primary lesion and outside the central nervous system are rarely reported in the
      literature. The case which is being presented is of a 53 year old man operated in
      2008 because of Glioblastoma multiforme IV WHO in the left periventricular
      parietal region, in which the main symptoms were the Gerstmann syndrome, mixed
      aphasia and memory disturbance. The patient was operated totally followed by
      adjuvant radiotherapy and chemotherapy. Two years later epileptic seizures and
      aphasia were intensified. Due to this adverse symptoms MRI was ordered, which
      revealed a tumor in the left periventricular temporal region in different
      location compared to the primary lesion. The patient was operated by temporal
      lobectomy. Histopathological diagnosis was Glioblastoma multiforme IV WHO.
      According to the literature we analyzed the natural GBM tumor features and
      factors responsible for possibility to appear of the same type of tumor in
      another location of the brain.

PMID- 22593994
TI  - [Associations of ICAM1 gene and VCAM1 promoter polymorphisms with transplanted
      kidney function].
AB  - INTRODUCTION: Transplantation is the preferred method of treatment of end-stage
      renal failure due to improvement in the quality of life and longer survival of
      patients. The process of graft rejection involves many mediators, including
      intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1
      (VCAM-1). Recent research has revealed the genetic background of the synthesis
      ofadhesins. Several polymorphisms of genes coding for ICAM-1 and VCAM-1 have been
      described which may be functionally important through various rates of synthesis
      of the mediator. Genetic differences in the synthesis of adhesion molecules may
      affect graft function and predispose to acute or chronic rejection. MATERIAL AND
      METHODS: The study enrolled 270 Caucasian whites (104 females and 166 males),
      aged 21 to 76 years (mean 47.63 +/- 12.96), who underwent allogenic renal
      grafting. Groups of patients with delayed graft function (n = 85), acute
      rejection (n = 70), and chronic allograft nephropathy were formed (n = 62).
      Biopsy of the renal graft was done to verify progressive loss of function.
      Polymorphisms were identified with PCR-RFLP. RESULTS AND CONCLUSIONS: It was
      found that the GG genotype of the rs5498 polymorphisms of the ICAM1 gene is a
      significant risk factor of acute rejection and is correlated with elevated
      concentrations of creatinine in allogenic renal graft recipients. The TC genotype
      of the rs3170794 polymorphism of the VCAM1 promoter may be a risk factor of acute
      rejection in allogenic renal graft recipients. The G allele of the rs5498
      polymorphism of the ICAM1 gene is significantly correlated with interstitial
      fibrosis and may also be correlated with other chronic histopathologic lesions
      seen in bioptates of the grafted kidney. There was no correlation of the
      rs1041163 and rs3170794 polymorphisms of the VCAM1 promoter with the severity of
      histopathologic lesions seen in bioptates of the grafted kidney.

PMID- 22593995
TI  - Response of malignant breast tumours to neoadjuvant chemotherapy evaluated with
      Tc-99m MIBI.
AB  - INTRODUCTION: The aim of this study was to assess the efficacy of Tc-99m
      sestamibi scintimammography in the prediction and evaluation of tumour response
      to neoadjuvant chemotherapy in patients with locally advanced breast cancer.
      MATERIALS AND METHODS: The subjects consisted of 14 female patients with
      unilateral locally advanced breast cancer eligible for anthracycline-based
      neoadjuvant chemotherapy followed by surgery. The patients underwent mastectomies
      with pathologic evaluation of the residual tumour size. The early and delayed
      static imaging were undertaken in all subjects at 10 and 120 minutes after
      intravenous injection with 720-1080 MBq of Tc-99m MIBI. Patients lay prone on the
      scintimammographic pad (provided by the IAEA). The acquisition included three
      positions: both lateral prone and anterior supine. Early, delayed tumour to
      background ratios (TBR) and washout rate (WOR) were calculated. Three sets of
      scintimammography images were obtained: baseline study (BL), the first follow-up
      study (FF) after two cycles of chemotherapy and the second follow-up (SF) scan on
      completion of chemotherapy and prior to surgery. Clinical response was evaluated
      following WHO criteria and classified as complete response (CR), partial response
      (PR), stable disease (StD) and progressive disease (PD). All patients underwent
      BS, seven of them FF and eight completed the study with SF. RESULTS: The only
      statistically significant differences in Student's t-test for matched pairs were
      found between mean values of TBR10 and TBR120 in BL and FF study however in the
      SF study it was not significant. Other differences between the mean values of
      TBR10, TBR120 and WOR in BL/FF, BL/SF and FF/SF studies were not statistically
      significant. CONCLUSION: The results obtained are encouraging, but further
      investigations are needed.

PMID- 22593996
TI  - [Genetic determinants of the alcohol dependence syndrome: searching for an
      endophenotype associated with sweet liking in families with alcohol addiction].
AB  - INTRODUCTION: The alcohol dependence syndrome is a disorder with a varying course
      of symptoms. Nevertheless, it is possible to distinguish subgroups of patients
      with a similar clinical picture. The purpose of this study was to determine the
      relationship between the sweet liking phenotype, a subtype of alcoholism
      according to Lesch and/or Cloninger and gene polymorphism of the DRD2
      dopaminergic system. MATERIAL AND METHODS: The study recruited 63 families
      (parents, alcohol-addicted son). Participants were interviewed for addiction
      (SSAGA, AUDIT) and were examined with the following questionnaires: MMSE, Beck
      Depression Inventory, Hamilton Anxiety Scale, and Lesch Typology Scale.
      Sensitivity to the sweet taste was tested and olfactometry was done. Polymorphism
      of the DRD2 gene was studied in exon 8, promoter region, and TaqI A1 locus.
      RESULTS: There was no correlation between type of alcoholism and sucrose
      preference among alcoholics. A correlation (p = 0.048) between sweet liking in
      fathers and sons was found, as well as between sucrose preference in alcoholic
      probands and non-alcoholic fathers (p = 0.0378). Sucrose preference correlated
      with the TaqI A1 allele of the DRD2 gene among alcoholics (p = 0.0016). Changes
      in the distribution of alleles and genotypes of the TaqI DRD2 polymorphism
      correlated with sucrose preference among alcoholics (p = 0.008). Similar
      relationships were not observed for parents. There was no correlation between the
      hedonistic response to sucrose solutions and other polymorphisms of the DRD2
      receptor gene in probands and parents.

PMID- 22593997
TI  - [The effect of tobacco smoke on the course and severity of inflammation in
      periodontal tissues].
AB  - INTRODUCTION: The spreading habit of smoking and the characteristic effects of
      components of tobacco smoke make nicotinism the main etiologic factor of many
      diseases and the factor which modifies their course. Inflammation of periodontal
      tissues is included here. The aim of this work was to investigate the effect of
      tobacco smoke on some clinical parameters of periodontal tissues in adults,
      habitual smokers of tobacco, who reported with chronic periodontitis, and whose
      general state of health was otherwise normal. MATERIAL AND METHODS: We enrolled
      85 patients with chronic periodontitis. Patients who smoked tobacco since at
      least 5 years without interruption, 10 cigarettes per day or more, were allocated
      to one group. The control group consisted of 47 patients who never smoked. We
      analyzed the Approximal Plaque Index (API), the modified Sulcular Bleeding Index
      (mSBI), pocket depth, clinical attachment loss, and number of teeth lost due to
      periodontitis. RESULTS AND CONCLUSIONS: The results of clinical tests were
      analyzed with Statistica P1 version 7.1 software package. Our analysis of API%
      demonstrated significantly higher values in habitual cigarette smokers. To the
      contrary, the Sulcular Bleeding Index (mSBI%) was significantly smaller in
      smokers. Mean pocket depth values and the clinical attachment loss were greater
      in habitual smokers. Tobacco smokers demonstrated significantly greater mean
      number of missing teeth due to chronic periodontitis. It follows that tobacco
      smoking is a relevant risk factor of periodontitis.

PMID- 22593998
TI  - [Ethyl alcohol and psychoactive drugs in patients with head and trunk injuries
      treated at the Department of General Surgery, Provincial Hospital in Siedlce].
AB  - INTRODUCTION: Drug abuse is a social, moral, and penal problem in Poland since
      many years. Ethyl alcohol remains the prime cause of concern. The effect of
      narcotics (including alcohol) on trauma has been the object of investigations for
      years. STUDY OBJECTIVES: 1) To determine the reliability of subjective assessment
      of sobriety of the patient by the physician. 2) To determine correlations between
      inebriety, duration of hospital stay, type and extent of surgical intervention,
      and death. 3) To compare blood alcohol content measured with an immunoenzyme
      assay and the reference gas chromatographic method (GC-headspace). 4) To assess
      correlations between GCS score, type of trauma, and blood alcohol content.
      MATERIAL: The study was done in 207 patients referred between 1.07.2008 and
      30.06.2009 to the hospital's emergency department due to trauma of the head
      and/or trunk. RESULTS: The significant role of ethyl alcohol in trauma of the
      head and trunk has been corroborated, in particular in young males admitted from
      Friday to Monday between 8:00 pm and 8:00 am. Ethyl alcohol in serum was detected
      in 34% of patients (40.1% of males and 12.5% of females) qualified to the test.
      The presence of alcohol in blood correlated with pedestrian or cyclist road
      accidents or violence (assault). Fractures of the skull and surgical treatment of
      wounds were significantly more frequent in inebriated patients. Inebriated
      patients were more inclined to leave the hospital on demand. According to the GCS
      score, 55.8% of patients with less than 15 points were inebriated. Disorders of
      speech were observed by the physician in only 47.9% of inebriated patients. The
      smell of alcohol on the breath was noted in 81.69% of inebriated patients and
      60.42% of them admitted drinking alcohol. Subjective assessment of
      sobriety/inebriety by the physician was correct in 81.7% of patients. The
      involvement of drugs acting like alcohol in trauma is marginal in Siedlce and its
      region. Xenobiotics were found in just three of 207 patients qualified to the
      test. The immunoenzyme assay used at the hospital for the measurement of blood
      alcohol content cannot serve for medicolegal purposes because its results are 1.2
      times above true values. This fact is particularly important for values between
      0.2 and 0.5 when legal responsibility is to be decided. CONCLUSIONS: 1) The
      accuracy of subjective assessment of sobriety of patients by the surgeon ranges
      from 48% to 82%. 2) Sobriety/inebriety correlated with circumstances of trauma,
      type of trauma, lower GCS score, and extent of surgical intervention. 3)
      Inebriety at admission did not correlate with the duration of hospital stay. 4)
      The immunoenzyme assay is sufficiently sensitive and accurate for diagnostic and
      clinical purposes. For medicolegal purposes, however, results provided by this
      method should be verified by gas chromatography.

PMID- 22593999
TI  - [The beginnings of antituberculosis service in Stettin. Hermann Braeuning--the
      first director of the Tuberculosis Hospital in Stettin-Hohenkrug (Szczecin
      Zdunowo)].
AB  - The beginnings of organized treatment for patients with tuberculosis (TB) in
      Stettin date back to the last decade of the nineteenth century and are traced to
      the Municipal Hospital in Stettin-Pommerensdorf (Szczecin-Pomorzany). Treatment
      of patients with TB in Pomerania improved with the opening of the Tuberculosis
      Hospital in Hohenkrug (Szczecin-Zdunowo). The author presents the history of the
      leading German Tuberculosis Hospital in Hohenkrug from its opening in 1915 till
      1945 highlighting its important role in the health care system of the entire
      Pomerania. Biographical details of the first director of the Hospital, Professor
      Hermann Braeuning, are provided. The Tuberculosis Hospital in Hohenkrug (Szczecin
      Zdunowo) quickly emerged as a modern research, educational, and therapeutic
      facility.

PMID- 22594000
TI  - The application of quality guidelines of the European Society of Endodontology in
      dental practice in Poland.
AB  - INTRODUCTION: We analyzed the application of endodontic quality guidelines of the
      European Society of Endodontology by Polish dentists: endodontists, other
      specialists, and dental general practitioners (DGPs). MATERIAL AND METHODS: A
      survey was done in 2008 among 544 dentists who attended hands-on sessions and
      lectures. The following data were collected: gender, professional experience,
      type of practice, specialization, and number of root fillings per week. Questions
      concerned the use of the rubber dam, electronic apex locator, radiographs,
      magnification by loupes or microscopes, nickel-titanium (NiTi) rotary system,
      warm gutta-percha, and treatment completed during no more than 2 visits. 3
      response options were available: often, occasionally, never. RESULTS: In the
      group we had 36.6% endodontists, 11.2% other specialists, and 52.2% DGPs. 95.9%
      of endodontists, 98.4% of other specialists, and 30.9% of DGPs (p <0.001) had at
      least 10 years of professional experience. 61.4% of endodontists performed more
      than 5 procedures per week, compared with 60% of DGPs and 42.4% of other
      specialists (p < 0.05). The use of radiographs, rubber dam, magnification, and
      NiTi rotary instruments was similar in the groups (p = NS). Dental general
      practitioners applied an electronic apex locator and completed the treatment
      during no more than 2 visits more often than endodontists and other specialists
      (p < 0.05). Dental general practitioners used warm gutta-percha more often than
      endodontists (p < 0.05). The percentage of dentists who declared use of all 7
      procedures as "often" or "occasionally" was low (8.2% - other specialists, 6% -
      DGPs, and 3% - endodontists; p = NS). CONCLUSIONS: The application of endodontic
      quality guidelines is not widespread among Polish dentists. Dentists who
      graduated more recently (DGPs) follow the guidelines more closely.

PMID- 22594001
TI  - [A contribution to the history of medicine in Poland: skeletal remains from a
      church hospital cemetery of the 14th 18th century in Leczyca (Province of Lodz)].
AB  - INTRODUCTION: We present the results of an anthropological and paleopathological
      analysis of 7 graves discovered at the site of a church-hospital complex existing
      in the 14th-18th century in Leczyca (province of Lodz). The aim was to determine
      whether the skeletons revealed features typical for the function of the complex.
      MATERIAL AND METHODS: The graves contained the remains of 8 persons: 4 men (2 of
      them aged 20-40 years and 2 aged 40-60 years), 2 women (aged 40-60 years), and 2
      children (one aged 2-4 years and a 10-month-old fetus or neonate buried together
      with one of the women). RESULTS: Four skeletons of adults (out of 5 skeletons in
      a condition adequate for the study) showed pathological (degenerative) and
      traumatic lesions. Pathologies of the masticatory organ (mainly intravital loss
      of teeth and recession of the alveolar process) were seen in all preserved adult
      skulls. CONCLUSIONS: The high incidence of pathologies indicates that we were
      dealing with the remains of patients of a hospital.

PMID- 22594002
TI  - [Deontologic aspects in publications of Bronislaw Wilhelm Sawicki (1860-1931)].
AB  - Bronislaw Wilhelm Sawicki (1860-1931), an eminent Warsaw surgeon who received an
      extensive education at foreign medical institutions, was an expert in various
      problems of hospital management. The complicated problems of education of
      physicians in the Russian sector of partitioned Poland (the Grand Duchy of Warsaw
      and the Congress Kingdom of Poland) formulated by Sawicki are presented in this
      work. Medical education in Western Europe especially in Germany, Austria and
      France, is described in detail. The problems of hospital assistants in the second
      part of the 19th and in the beginning of the 20th century are discussed.

PMID- 22594003
TI  - The FDA and the medical device approval process.

PMID- 22594004
TI  - Closing the sale of a healthcare business.

PMID- 22594005
TI  - [Drug allergies].

PMID- 22594006
TI  - [Hypersensitivity to proton pump inhibitors].
AB  - Hypersensitivity to proton pump inhibitors (PPI) is rare but potentially severe.
      An increase in hypersensitivity reactions to PPI is expected as these drugs are
      widely prescribed and some have become available over-the-counter. Allergy to PPI
      has to be considered in patients presenting anaphylaxis, late-type skin rashes,
      interstitial nephritis and other organ involvement suspicious to be drug-induced.
      Cross-reactivity between PPI is of concern, as they are closely related in
      structure. Skin prick- and intradermal testing are reliable tools to confirm
      immediate-type allergy to one PPI compound and search for safe alternatives. We
      review the literature on immediate and delayed hypersensitivity to these drugs.

PMID- 22594007
TI  - [Allergy to beta-lactam antibiotics].
AB  - Beta-lactam antibiotics allergies are common. Up to 10% of the population
      describe a former allergy to penicillins. However only 10 to 15% of these
      individuals are actually allergic. In most cases, beta-lactam antibiotics will be
      avoided and replaced by other antibiotics such as quinolones. This fear of a
      serious allergic reaction has an economic impact and may lead to the emergence of
      antibiotic resistance. A thorough allergic work-up can accurately determine true
      allergic patients. Most of the patients with a proven allergy will be able to
      tolerate other antibiotics belonging to the beta-lactam family. This article
      focuses on the management of beta-lactam allergic patients.

PMID- 22594008
TI  - [Sjogren's syndrome: a new approach to treatment].
AB  - Sodgren's syndrome treatment has essentially been based on symptomatic approach
      and has been of limited efficacy. Novel biological therapies targeting B cells, a
      key player in the pathophysiology of the syndrome, have recently been tested in
      controlled clinical trials and raise the hope of improving glandular and
      extraglandular manifestations of Soigren's syndrome.

PMID- 22594009
TI  - [Central neuropsychiatric involvement in systemic lupus erythematosus].
AB  - About one third of patients with systemic lupus erythematosus (SLE) will present
      neurological or psychiatric symptoms in the course of the disease. Before
      attributing neuro-psychiatric illness to SLE, other causes have to be excluded,
      such as infections and treatment-related toxicity. Some manifestations of
      neuropsychiatric SLE (NPSLE) reflect active systemic disease, while other arise
      from chronic damage and may occur during apparent remission. Many clinical
      pictures are associated with antibodies, such as those targeting phospholipids, N
      methyl-D-aspartate-receptor and anti-ribosomal P protein. This review discusses
      clinical manifestations and pathogenesis of central NPSLE, with a focus on the
      principal antibodies associated and other diagnostic tools at hand.

PMID- 22594010
TI  - [Eosinophllic fasciitis (Shulman disease)].
AB  - Eosinophilic fasciitis is a rare connective tissue disease, described by Shulman
      in 1974. This syndrome is characterized by a symmetrical swelling of the skin
      associated with eosinophilia. A progressive induration of the skin replaces the
      swelling. Arms and legs are the most affected sites. The face and hands are
      usually not involved and the patients don't complain of Raynaud phenomenon. No
      circulating autoantibodies are found. Diagnosis is made with history, MRI and
      histology. MRI detects fascial thickening and contrast enhancement of this
      fascia. A full thickness skin to muscle biopsy is necessary to confirm the
      diagnosis. It shows an inflammation and thickening of the fascia with lymphocytes
      and plasmocytes. High doses of corticosteroids are reported to be effective in
      more than 70% of the cases. Immunosuppressive drugs are sometimes necessary to
      induce clinical remission.

PMID- 22594011
TI  - [Common variable immune deficiency: what you need to know].
AB  - Common variable immune deficiency is the most frequent primary immune deficiency,
      characterized mainly by a disorder of B lymphocytes differentiation and a deficit
      in immunoglobulins. The clinical manifestations include recurrent infections, non
      infectious lung and digestive involvements, autoimmune diseases, and an increased
      susceptibility to cancers. Recent breakthroughs have been made in the
      understanding of some genetic mechanisms of the disease. Replacement therapy with
      intravenous immunoglobulins remains the treatment of choice, which allows
      significant improvement in the survival and quality of life. However progress
      should be made in the understanding of the pathophysiology and in the early
      detection of this disease, since a delay in the diagnosis may have harmful
      consequences in terms of morbidity and mortality.

PMID- 22594012
TI  - [The revival of the digital rectal exam?].

PMID- 22594013
TI  - [Eradicating Down syndrome].

PMID- 22594014
TI  - [Psychiatry according to Felix Guattari (1)].

PMID- 22594015
TI  - [Managed care, dream and reality].

PMID- 22594016
TI  - Peter Rossdale's scientific contribution to equine perinatology.

PMID- 22594017
TI  - Multicentre clinical research and the veterinary clinician.

PMID- 22594018
TI  - The impact of peer-reviewed literature on equine neonatal care.

PMID- 22594019
TI  - Relationship between infection, inflammation and premature parturition in mares
      with experimentally induced placentitis.
AB  - REASONS FOR PERFORMING THE STUDY: Ascending placentitis results in premature
      birth and high foal mortality. By understanding how placentitis induces premature
      delivery, it may be possible to develop diagnostic markers and to delay premature
      delivery pharmacologically, thereby decreasing perinatal foal mortality.
      OBJECTIVE: To identify relationships between bacterial infection, inflammation
      and premature parturition in mares with experimentally induced placentitis.
      MATERIALS AND METHODS: Experiment 1: Concentrations of allantoic fluid
      prostaglandins (PGs) F2alpha and E2 were measured in 8 mares after intracervical
      inoculation with Streptococcus equi ssp. zooepidemicus (at Days 285-291 of
      gestation) until parturition and compared with controls (n = 4). Experiment 2:
      mRNA expression of interleukin (IL)-1beta, IL-6, tumour necrosis factor (TNF)
      alpha and IL-8 in the chorioallantois from inoculated mares in Experiment 1 were
      compared with 7 mares that foaled normally. RESULTS: Bacterial inoculation
      resulted in 7 aborted fetuses and birth of one premature, viable foal. Infection
      was associated with inflammation of the chorioallantois in the region of the
      cervical star, isolation of bacteria and high concentrations of PGE2 and
      PGF2alpha in allantoic fluid obtained within 48 h of delivery (P = 0.04).
      Chorioallantois from all mares expressed mRNA for IL-8, TNF-alpha, IL-6 and IL
      1beta. Experimentally infected mares expressed more mRNA for IL-6 (P = 0.003) and
      IL-8 (P = 0.009) in the cervical star region and more mRNA for IL-6 (P = 0.004)
      in tissues from placental horns than control mares. CONCLUSIONS AND CLINICAL
      RELEVANCE: Bacterial placentitis may result in liberation of cytokines from the
      chorioallantois and prostaglandin formation leading to abortion or birth of a
      precociously mature foal.

PMID- 22594020
TI  - Uterine haemodynamics in young and aged pregnant mares measured using Doppler
      ultrasonography.
AB  - REASON FOR PERFORMING STUDY: Aged mares with endometrosis suffer higher rates of
      pregnancy loss than young mares, due to poor placental development. Reduced
      uterine blood supply may be one contributory factor. OBJECTIVES: To measure
      uterine artery (UA) blood flow and other Doppler indices throughout pregnancy and
      compare placental and foal development in young mares and aged mares. METHODS:
      Thoroughbred mares were grouped according to age and endometrial biopsy score: 1)
      6 young mares (mean age 7.3 years, Category ); 2) 6 aged mares (mean age 18.3
      years, Category II). Vascular pathology was nil or mild except in one aged mare
      with moderate perivasculitis. Both UA were scanned fortnightly throughout
      pregnancy. Total blood flow volume (BFV, ml/min/kg bwt), peak systolic velocity
      (PSV, cm/s) and resistance index (RI) were determined by pulsed wave, Doppler
      ultrasound and UA diameter using B-mode. Mixed-effects regression analyses were
      used to relate vascular parameters with different predictive variables, whilst
      accounting for the multiple repeated measurements taken from individual horses
      through the duration of their pregnancies. RESULTS: PSV, RI and total BFV were
      best predicted by stage of pregnancy (P < 0.001; r2 > 78%). The UA diameter was
      also associated with stage of pregnancy (P < 0.001; r2 = 87%) and was
      significantly greater in the gravid horn (P < 0.001). There was a tendency for
      lower total BFV in older mares (P < 0.05) and they delivered lighter foals than
      young mares (P < 0.05). Gross placental morphometry was similar, but microscopic
      surface density of the microvilli was lower (P < 0.02), in aged than young mares.
      CONCLUSIONS AND POTENTIAL RELEVANCE: Increased uterine blood flow and decreased
      vascular resistance reflect fetal growth and development of the placental
      microcirculation. Older mares have poorer placental microvillus development and
      lighter foals with reduced UA blood flow. Poor uterine blood flow may be an
      important contributory factor for pregnancy loss in aged mares.

PMID- 22594021
TI  - Parturition, dystocia and foal survival: a retrospective study of 1047 births.
AB  - REASON FOR PERFORMING STUDY: An understanding of the normal events of foaling,
      causes of dystocia and clinical outcomes is important for equine practitioners.
      OBJECTIVES: The goals of the present study were to: 1) evaluate factors that
      influence gestation length; 2) report duration of Stage II labour; 3) determine
      the frequency of dystocia and premature placental separation; and 4) determine
      the relationship between problems at foaling and foal survival. MATERIALS AND
      METHODS: Foaling records of 1047 mare births were evaluated. RESULTS: The average
      gestation length was 342.7 days [corrected] +/- 0.4 days, with no effect of mare
      age or breed observed. Mares carrying male fetuses had a longer gestation (P < or
      = 0.001) than mares carrying female fetuses. A majority (52.8%) of mares foaled
      at night between 2000 h and 0200 h when the facility was quiet. Dystocia occurred
      in 10.1% of all births and the incidence rate was higher in Thoroughbred mares
      than in Quarter Horse mares. The most common cause of dystocia was abnormalities
      of fetal posture. A delay in foal delivery beyond 40 min of Stage II of labour
      was associated with a significant increase in foal mortality. In addition, an
      increase in foal morbidity and mortality was noted when the interval from birth
      to standing or birth to nursing was prolonged. CONCLUSION: Early detection and
      rapid appropriate intervention are critical to foal survival in an equine
      dystocia. POTENTIAL RELEVANCE: Equine veterinarians should counsel horse owners
      that early recognition of a foaling problem and rapid, appropriate intervention
      are critical to the survival of a foal.

PMID- 22594022
TI  - The impact of birthweight on mare health and reproductive efficiency, and foal
      health and subsequent racing performance.
AB  - REASONS FOR PERFORMING STUDY: Although low birthweight is a risk factor for
      neonatal illness, the impact of high birthweight on the health of foals and
      mares, and on the foals' long-term athletic capability, is unknown. OBJECTIVES:
      To investigate whether: 1) foals that are excessively heavy are associated with
      an increased prevalence of maternal illness in the first month post partum and
      reproductive dysfunction in the following season; 2) excessively light or heavy
      foals are at an increased risk of illness in the first month of life; and 3)
      birthweight is associated with racing success. METHODS: Veterinary records from
      230 Thoroughbred mares and 409 foalings were reviewed. Data relating to foaling,
      foal and mare health during the first month postpartum and subsequent breeding
      efficiency were extracted. Foals' racing records were obtained and the
      association between birthweight and these outcomes examined. RESULTS: Mares with
      heavy foals had a higher prevalence of minor nonreproductive problems than those
      with light and average foals. Compared to average foals, placental weight was
      lower in the light group and higher in the heavy group. Light foals took longer
      to stand, nurse and pass meconium, whereas gestation period and duration of Stage
      2 parturition were longer in heavy foals. Heavy foals were at increased risk of
      nonseptic musculoskeletal conditions and conformational defects. Birthweight was
      not associated with racing outcomes. CONCLUSIONS: High birthweight was associated
      with increased prevalence of neonatal musculoskeletal conditions but birthweight
      did not have a major impact on mares' health and reproductive efficiency,
      orfoals' racing success. POTENTIAL RELEVANCE: These data add to the understanding
      of the impact of birthweight on short- and long-term health outcomes in mares and
      foals.

PMID- 22594023
TI  - Pancreatic endocrine function in newborn pony foals after induced or spontaneous
      delivery at term.
AB  - REASONS FOR PERFORMING STUDY: During the switch from parenteral to enteral
      nutrition at birth, endocrine glands such as the pancreas must assume a
      glucoregulatory role for the first time if the neonate is to survive the
      transition to extrauterine life. OBJECTIVES: To determine the adaptations in
      pancreatic endocrine function during the neonatal period in term pony foals
      delivered by different methods. METHODS: By measuring insulin and glucagon
      concentrations, pancreatic alpha and beta cell responses to exogenous glucose
      (0.5 g/kg bwt) and arginine (100 mg/kg bwt) and to endogenous muzzling for 90 min
      were determined periodically over the first 10 post natal days in foals born
      spontaneously (n = 8) or by induction of labour with oxytocin at term (n = 7).
      RESULTS: Pancreatic alpha and beta cell function changed with post natal age in a
      manner related to the method of delivery. Induced foals had 2-3 fold greater beta
      cell responses to exogenous glucose and arginine, despite similar glucose and
      alpha-amino nitrogen clearances compared with spontaneously delivered foals.
      Pancreatic beta cell responses to glucose decreased by 50% while those to
      arginine doubled with increasing age in induced but not spontaneously delivered
      foals. In contrast, pancreatic alpha cell responses to arginine doubled with
      increasing age in foals born spontaneously but not by induction. These
      differences in pancreatic endocrine cell function with delivery method were
      associated with 2-3 fold higher cortisol levels in the induced foals and with
      differences in the absolute and age-related changes in basal concentrations of
      glucose, alpha-amino nitrogen and insulin. CONCLUSIONS: Induced delivery leads to
      changes in pancreatic beta cell sensitivity to glucose and/or tissue insulin
      resistance in association with persistent neonatal hypercortisolaemia. POTENTIAL
      RELEVANCE: The altered post natal development of pancreatic endocrine function
      with induced delivery may compromise glucoregulation and adaptation to enteral
      nutrition in neonatal foals with potential consequences long after birth.

PMID- 22594024
TI  - Hypothalamic-pituitary-adrenal axis function in pony foals after neonatal ACTH
      induced glucocorticoid overexposure.
AB  - REASONS FOR PERFORMING THE STUDY: The effects of overexposure to glucocorticoids
      during early life of the foal on the subsequent HPA programming of the
      hypothalamic-pituitary-adrenal axis are unknown. OBJECTIVES: To test the
      hypotheses that excess glucocorticoid exposure in early life subsequently
      increases both basal plasma concentrations of cortisol and the adrenocortical
      responsiveness to exogenous adrenocorticotropic hormone (ACTH). METHODS: Foals
      received either saline (0.9% NaCl, n = 9) or long-acting ACTH (0.125 mg i.m.
      b.i.d., n = 6) for 5 days from Day 1 to increase endogenous cortisol
      concentrations. Long-term indwelling catheters were inserted under local
      anaesthesia into the jugular veins of foals aged 2 and 12 weeks. After recovery,
      short-acting ACTH1-24 was given as a single i.v. injection (2 microg/kg bwt) and
      blood samples were taken at 5-30 min intervals before and after ACTH
      administration to measure plasma cortisol concentrations. RESULTS: Basal plasma
      cortisol concentrations were higher in ACTH- than in saline-treated foals at age
      3 weeks, but not at 13 weeks. There were no significant differences in either the
      time profile or the area under the cortisol curve in response to ACTH between the
      2 groups. CONCLUSIONS: These data suggest that ACTH-induced overexposure to
      glucocorticoids during early post natal life of the foal does not have a
      programming effect on HPA axis function at 13 weeks. In foals, the effects of
      ACTH-induced overexposure to glucocorticoids, if any, may not become apparent
      until much later in life in a long-lived species such as the horse. POTENTIAL
      RELEVANCE: These studies suggest that clinical and other stressful conditions
      that raise plasma cortisol concentrations during early life are unlikely to
      programme cardiovascular and metabolic function in horses in the short term.

PMID- 22594025
TI  - Presumptive nonthyroidal illness syndrome in critically ill foals.
AB  - REASONS FOR PERFORMING THE STUDY: Hypothalamic-pituitary-thyroid (HPT) axis
      dysfunction is associated with morbidity and mortality in critically ill people.
      To date, investigations of HPT axis in critically ill foals are limited.
      OBJECTIVES: To document the occurrence of low thyroid hormone concentrations
      (presumptive nonthyroidal illness syndrome; NTIS) in critically ill newborn foals
      and investigate whether NTIS is associated with severity of disease and outcome.
      HYPOTHESIS: NTIS occurs frequently in foals with sepsis and is associated with
      sepsis score and outcome. Reverse T3 (rT3) concentrations will be increased in
      septic foals and highest in nonsurvivors. METHODS: Thyroid hormones (total and
      free thyroxine [TT4 and fT4], total and free tri-iodothyronine [TT3 and fT3],
      reverse T3 [rT3]) were prospectively measured in healthy, sick nonseptic and
      septic foals. Clinical and laboratory information was retrieved from the medical
      records. Hormones were measured by validated radioimmunoassays. RESULTS:
      Concentrations of all thyroid hormones except rT3 (P = 0.69) were decreased in
      septic and sick nonseptic foals (P < 0.01). Reductions in hormone concentrations
      were associated with an increased sepsis score (P < 0.01). Nonsurviving septic
      foals had lower TT4, fT4, TT3 and fT3 concentrations than surviving septic foals
      (P < 0.01). rT3 concentrations were higher in nonsurviving septic prematurefoals
      than surviving septic premature foals (P < 0.05). CONCLUSIONS: NTIS (euthyroid
      sick syndrome) is frequently observed in critically ill and premature foals, and
      associated with severity of disease and mortality. POTENTIAL RELEVANCE: More
      research is needed to better understand the mechanism of this finding and
      determine whether manipulation of the HPT axis or thyroid replacement therapy
      could be beneficial.

PMID- 22594026
TI  - Energy expenditure of critically ill neonatal foals.
AB  - REASONS FOR PERFORMING STUDY: Nutritional support in critically ill neonatal
      foals is of great importance given their high metabolic rate and minimal stores
      of energy and protein. Nutrient requirements of healthy growing foals have been
      estimated based on daily milk intake; however, little is known about the resting
      energy expenditure (REE) of sick foals. OBJECTIVES: To determine REE in
      critically ill neonatal foals (sepsis and/or hypoxic-ischaemic encephalopathy
      [HIE] and compare this with REE in control foals. METHODS: Critically ill newborn
      foals admitted to the Fundacio Hospital Clinic Veterinari, Universitat Autonoma
      de Barcelona, Spain from March 2009 to February 2011 were included in this study.
      Healthy neonatal foals and foals with nonsystemic conditions were used as
      controls. Oxygen consumption and CO2 production were measured with a respiratory
      monitor connected to a tight fitting facemask and REE (kcal/kg bwt/day) was
      calculated with the abbreviated Weir formula. Measurements were performed within
      24 h of admission and repeatedly during hospitalisation. RESULTS: Twenty-seven
      foals were included (16 critically ill foals and 11 controls) and a total of 47
      measurements were performed. In the critically ill, REE was reduced (mean +/-
      s.e. 49.5 +/- 2.1 kcal/kg bwt/day) on admission relative to the controls. In
      surviving foals (n = 5), REE before hospital discharge was not different (68.4 +/
      7.0 kcal/kg bwt/day) from control foals (64.8 +/- 2.7 kcal/kg bwt/day).
      CONCLUSIONS: REE was lower in critically ill foals upon admission (40-50 kcal/kg
      bwt/day) and normalised before hospital discharge (60-80 kcal/kg bwt/day).
      POTENTIAL RELEVANCE: Critically ill neonatal foals tolerating enteral feeding
      would receive approximately their REE when given 10% of their bodyweight in
      mare's milk daily. For sick neonates unable to tolerate enteral nutrition,
      provision of 50 kcal/kg bwt/day would be a reasonable goal for parenteral
      nutrition.

PMID- 22594027
TI  - Comparing the pharmacokinetics of a fourth generation cephalosporin in three
      different age groups of New Forest ponies.
AB  - REASONS FOR PERFORMING STUDY: To compare the pharmacokinetics of the fourth
      generation cephalosporin, cefquinome, in neonatal foals, 6-week-old foals and
      mature New Forest ponies in order to recommend appropriate dosage regimens for
      use of this drug. METHODS: Cefquinome was administered i.v. at 1 mg/kg bwt twice
      a day (q. 12 h), 1 mg/kg bwt 3 times a day (q. 8 h) or 4.5 mg/kg bwt q. 12 h to
      each age group (n = 6). Plasma cefquinome concentrations were analysed using high
      performance liquid chromatography combined with electrospray tandem mass
      spectrometry. RESULTS: Both foal age groups had comparable pharmacokinetic data
      except for the volume of distribution at a steady-state (Vss), total body
      clearance (ClB) and mean residence time (MRT). Both ClB and MRT decreased as the
      age of the foals increased. Values of area under the curve increased, in a dose
      dependent manner, with significant increases for all age groups following
      administration of 4.5 mg/kg bwt q. 12 h. Total body clearance did not have
      comparable dose dependency. CONCLUSIONS: Cefquinome can be given at a dose of 1
      mg/kg bwt q. 12 h for the treatment of infections caused by susceptible pathogens
      with MIC < 0.125 microg/ml. A higher dose of 4.5 mg/kg bwt q. 12 h is recommended
      for the treatment of bacterial pathogens with minimal inhibitory concentration
      (MIC) 0.125-0.5 microg/ml POTENTIAL RELEVANCE: Commonly used dosing regimens
      should be critically evaluated in neonatal foals due to the higher volume of
      distribution of less lipophilic drugs in this age group.

PMID- 22594028
TI  - Association of admission L-lactate concentration in hospitalised equine neonates
      with presenting complaint, periparturient events, clinical diagnosis and outcome:
      a prospective multicentre study.
AB  - REASONS FOR PERFORMING THE STUDY: Admission L-lactate concentration is a useful
      and commonly measured biomarker not previously prospectively evaluated in a large
      multicentre study of critically ill neonatal foals. OBJECTIVES: To evaluate
      overall outcome and the association of survival and L-lactate concentration at
      admission ([LAC]ADMIT) by periparturient history, presenting complaint and
      clinicians' major diagnosis for ill neonatal foals. METHODS: Thirteen university
      and private equine referral hospitals enrolled 643 foals over the 2008 foaling
      season. Case details, historical, clinical and clinicopathological data were
      entered into standardised spreadsheets then unified for analysis. RESULTS:
      Overall survival was 79% (505/643). Risk of nonsurvival increased with each 1
      mmol/l increase in [LAC]ADMIT (odds ratio 1.14, P < 0.001). Mean arterial
      pressure had a small (r2 = 19.1) but significant (P < 0.001) association with
      [LAC]ADMIT. Foals experiencing known dystocia or premature placental separation
      had increased [LAC]ADMIT (P < 0.001). Single umbilical problems (excluding
      uroperitoneum), meconium impaction only and failure of passive transfer of
      immunity only had 100% survival. Six clinicians' major diagnoses had increased
      odds of nonsurvival for each 1 mmol/l increase in [LAC]ADMIT: 'sepsis';
      'unspecified enterocolitis'; 'unspecified colic'; 'unspecified trauma'; 'immune
      related (not failure of passive transfer of immunity)' and 'respiratory only'.
      CONCLUSIONS AND POTENTIAL RELEVANCE: Survival of critically ill foals is good but
      varies with peripartum history, presenting complaint and clinicians' major
      diagnosis. L-lactate concentration at admission proves its utility as a valuable
      prognostic biomarker in neonatal foals and its utility appears to vary with
      peripartum history and clinicians' major diagnosis.

PMID- 22594029
TI  - The importance of ultrasonographic pneumatosis intestinalis in equine neonatal
      gastrointestinal disease.
AB  - REASONS FOR PERFORMING STUDY: Recognising the presence of a necrotising component
      of the gastrointestinal disease may be clinically useful in ill equine neonates.
      OBJECTIVES: To study the importance of abdominal sonograms in neonatal foals
      suffering from gastrointestinal conditions and to describe the clinical features
      of necrotising gastrointestinal disease. HYPOTHESIS: There is a subgroup of
      neonates with sonographically detectable pneumatosis intestinalis (PI),
      reflecting a necrotising disease. METHODS: Records of foals aged < or = 7 days
      hospitalised from 2005 to 2009 with signs of gastrointestinal disease were
      evaluated (n = 89). The association of sonographic, clinical and
      clinicopathological signs with necrotising gastrointestinal disease and outcome
      was determined. RESULTS: PI was imaged in 19 foals. Twenty-seven foals were
      classified as having necrotising gastrointestinal disease based on the presence
      of gastrointestinal signs (colic, diarrhoea, gastric reflux or abdominal
      distension) and sonographic PI (n = 19), surgical (n = 2) or pathological (n = 6)
      evidence of gastrointestinal necrosis. There was a difference between survival
      rate in foals with and without necrotising disease (33.3 and 69.4%, respectively,
      P = 0.005) or foals with and without PI detected sonographically (36.8 and 72.1%,
      respectively, P = 0.023). PI was the only sonographic finding associated with
      outcome. Prematurity, the presence of blood in the faeces, gastric reflux,
      abdominal distension, abnormal echogenicity of the colon and the lowest white
      blood cell count during hospitalisation were associated with necrotising
      gastrointestinal disease (P < 0.05). CONCLUSIONS AND POTENTIAL RELEVANCE:
      Abdominal sonograms have prognostic value in neonatal gastrointestinal disease.
      PI and the presence of necrotising gastrointestinal disease were common and
      associated with a poor prognosis.

PMID- 22594030
TI  - Intraoperator, intraobserver and interoperator variability of echocardiographic
      measurements in healthy foals.
AB  - REASON FOR PERFORMING STUDY: The repeatability of various echocardiographic
      measurements is unknown. OBJECTIVES: To determine the intraoperator,
      intraobserver and interoperator variability of echocardiographic measures in
      healthy foals. METHODS: Echocardiographic examinations were carried out on 6
      healthy foals by 3 experienced echocardiographers. Intraoperator variability was
      determined by having a single echocardiographer obtain and measure images from 6
      foals scanned on 3 consecutive days. Interoperator and intraobserver variability
      were determined by having 3 echocardiographers each obtain images from an
      additional 6 sedated foals. Within-day interoperator variability was determined
      by having each echocardiographer measure their own images. Intraobserver
      variability was determined by having a single echocardiographer measure images
      obtained by all 3 echocardiographers. The coefficient of variation (CV) and
      standard error were calculated for each measure. RESULTS: The variability for
      most measurements was either very low (CV < 5%) or low (CV = 5-15%). Measurements
      of right ventricular internal diameter (RVID) in systole and E-point to septal
      separation (EPSS) showed moderate (CV 15-25%) to high variability (CV > 25%) in
      all 3 categories. Measurements of the left ventricular ejection time (LVET) and
      velocity time integral from the right parasternal long axis view of right outflow
      tract in the fourth intercostal space showed moderate intraoperator variability.
      Measurements of the LVET, RVID in diastole and left atrial appendage (LAA) showed
      moderate interoperator variability and measurements of the RVID in diastole and
      acceleration time from the short axis view of the right outflow tract in the
      right third intercostal space showed moderate interobserver variability.
      CONCLUSION: The intraoperator, intraobserver and interoperatorvariabilities for
      most echocardiographic measurements in foals are low. POTENTIAL RELEVANCE: Most
      standard transthoracic echocardiographic measurements in foals have a low enough
      variability to warrant their use in serial clinical evaluations or experimental
      studies. Repeated measurements of RVID, EPSS, LVET and LAA should be interpreted
      with caution.

PMID- 22594031
TI  - Prevalence of gastric and duodenal ulceration in 691 nonsurviving foals (1995
      2006).
AB  - REASON FOR PERFORMING STUDY: Gastric ulcer disease is reported to be a
      significant cause of morbidity in foals, but the prevalence of ulcers in this
      population has not recently been evaluated. OBJECTIVES: To determine the
      prevalence of gastric and duodenal ulceration in nonsurviving foals, and the
      association of ulceration with the body system of primary diagnosis. Secondary
      objectives were to evaluate a potential association between age and ulcer
      prevalence and to evaluate the use of antacid medication in the neonatal hospital
      population during the study years. METHODS: Necropsy records were searched for
      all equine accessions from 1995 to 2006. Foals aged from one day to 6 months were
      included. Year, age, breed, sex, diagnosis and the presence of glandular,
      nonglandularand/or duodenal ulceration were recorded. Diagnoses were divided into
      groups based on the body system of primary diagnosis, with multiple diagnoses
      possible. A computerised database was searched for antacid treatment of all
      neonatal admissions. RESULTS: The overall prevalence of ulcers was 22%, with
      nonglandular ulcers predominating. Ulceration was significantly associated with
      gastrointestinal disease. There was no significant change in ulcer prevalence
      over time, although there was a significant decrease in the use of antacid
      medications in the later study years. Neonatal foals (< 1 month) had a lower
      ulcer prevalence than olderfoals. CONCLUSIONS: The prevalence of ulcers in foals,
      although low, has remained stable over time. Gastric or duodenal ulcers are
      associated with a primary diagnosis of gastrointestinal disease and are less
      prevalent in neonates. POTENTIAL RELEVANCE: The prevalence of ulcers in
      nonsurviving foals is low. Foals with gastrointestinal disease are more likely to
      have ulcers than foals with other primary diagnoses, and older foals are more
      likely to have ulceration than neonates. The prevalence of ulceration did not
      appear to be related to hospital-wide antacid medication use in neonates.

PMID- 22594032
TI  - Treatment with histamine-type 2 receptor antagonists and omeprazole increase the
      risk of diarrhoea in neonatal foals treated in intensive care units.
AB  - REASONS FOR PERFORMING STUDY: The use of anti-ulcer medication in the neonatal
      intensive care unit (ICU) is common due to the concern for development of
      catastrophic gastric ulcerdisease. In man, however, the use of acid-suppressive
      medication has been shown in some studies to be a substantial riskfactorfor the
      development of Clostridium difficile-associated diarrhoea (CDAD), bacteraemia and
      neonatal sepsis. OBJECTIVE: The purpose of the study reported herein is to
      evaluate the influence of anti-ulcer medications on the development of diarrhoea
      in the neonatalfoal. HYPOTHESIS: The use of anti-ulcer medication does not alter
      the incidence of diarrhoea in foals treated in an ICU. METHODS: The records of
      1710 foals from 6 different equine hospitals were examined and the use of anti
      ulcer drugs was recorded. The presence of in-hospital acquired diarrhoea, CDAD,
      Clostridium perfringens-associated diarrhoea, neonatal sepsis and salmonellosis
      were documented. In addition, the presence of gastric ulceration, duration of
      hospital stay and short-term outcome were examined. RESULTS: The use of anti
      ulcer medications increased the odds of in-hospital diarrhoea by 2.0 (95% CI 1.4
      2.9; P < 0.0001), relative to the use of no anti-ulcer medication. There was no
      significant association of anti-ulcer medication with CDAD (P = 0.3189) (OR 2.0;
      95% CI 0.4-9.5). Further, results indicated that decreased prevalence of gastric
      ulceration was not associated with use of anti-ulcer drugs among foals in the
      study for which these data were known (P = 0.5522). CONCLUSIONS: Use of anti
      ulcer drugs increases the odds of developing diarrhoea, and may not reduce the
      incidence of gastric ulceration in hospitalised equine neonates. POTENTIAL
      RELEVANCE: The use of anti-ulcer drugs in neonatal foals being treated in a
      hospital setting should be carefully evaluated on an individual basis to
      determine if such use is warranted.

PMID- 22594033
TI  - Hospital treatment as a foal does not adversely affect future sales performance
      in Thoroughbred horses.
AB  - REASONS FOR PERFORMING STUDY: Many Thoroughbred foals are intended to be sold at
      public auction. The impact of disease conditions necessitating hospital treatment
      as a foal on future sales performance is unknown. OBJECTIVES: To determine
      whether Thoroughbred horses that were treated in a hospital before age 125 days
      and presented to public auction sell for a different mean price than controls.
      METHODS: Foals aged < 125 days, treated at a hospital in Ireland in 2007 or 2008
      and presented for sale to a public auction recorded on a publicly accessible
      database were selected for inclusion in the study. The sales outcome of these
      subjects was compared to that of 6 controls for each subject, consisting of the 3
      horses that were presented to the same sale immediately before and immediately
      after the subject. Results were controlled for the sale at which the animal
      presented and the sex of the subject and controls. RESULTS: Sixty-three subjects
      were presented to public auction: 19 at the foal sales, 39 at the yearling sales
      and 5 at the 2-year-old sales. Forty-five subjects were sold. There was no
      difference in the mean sales price (subjects Euros 38,207; controls Euros 35,026)
      or percentage of animals sold (subjects 71.4%; controls 66.4%) between subjects
      and controls. CONCLUSIONS: If Thoroughbred horses are presented for public
      auction following hospital treatment as a foal, there is no impact on sales
      outcome. POTENTIAL RELEVANCE: This information may help commercial breeders of
      Thoroughbred foals make informed decisions about treatment of their foals.

PMID- 22594034
TI  - Necrosis of the femoral condyles in a four-week-old foal: clinical, imaging and
      histopathological features.
AB  - A 4-week-old Thoroughbred filly foal with a history of sepsis was evaluated for
      right hindlimb lameness. Bilateral femoropatellar and femorotibial joint
      effusions were detected. Ultrasonography and radiography of the right stifle
      revealed signs of joint collapse and periarticular swelling. Computed tomography
      revealed abnormalities in the bone density of the medial femoral condyle of the
      right hindlimb and lateral femoral condyle of the left hindlimb. Euthanasia was
      recommended based on the severity of the lesions. Gross and microscopic
      examinations revealed extensive separation of the articular-epiphyseal cartilage
      complex from the subchondral bone of the femoral condyles. The histological
      features suggest an ischaemic aetiology; comparisons are made with lesions of
      osteochondrosis and avascular necrosis of bone.

PMID- 22594035
TI  - Acute pancreatitis in two five-day-old Appaloosa foals.
AB  - Severe acute pancreatitis (SAP) in foals is rare and treatment has not been
      documented. This paper describes the clinical, haematological and
      ultrasonographic findings as well as attempted treatment of SAP in two 5-day-old
      Appaloosa fillies. Clinical signs, including colic, diarrhoea and coma, may be
      mistaken for sepsis or neonatal encephalopathy. Hyperlipaemic serum and
      peritoneal fluid, and elevated serum and peritoneal fluid amylase and lipase
      activities aided the diagnosis. Severe acute pancreatitis should be included as a
      differential in an acutely ill foal with diarrhoea, colic, cerebral cortica
      dysfunction and hyperlipaemia.

PMID- 22594036
TI  - Clinical findings in 10 foals with bacterial meningoencephalitis.
AB  - REASONS FOR PERFORMING THE STUDY: Bacterial meningoencephalitis is a severe
      complication in septic foals and there is scarce and often unclear information in
      the equine literature. OBJECTIVES: To report the most frequent clinical signs,
      clinicopathological findings, causative agents, treatments given and outcome of a
      group of foals with confirmed bacterial meningoencephalitis. METHODS: Foals aged
      < 6 months of age admitted to the Universitat Autonoma de Barcelona (2004-2009)
      with confirmed bacterial meningoencephalitis were retrospectively included in the
      study Diagnosis of bacterial meningoencephalitis was made by cerebrospinal fluid
      (CSF) culture, CSF analysis consistent with bacterial infection, observation of
      bacteria in CSF cytology or postmortem confirmation. RESULTS: Nine neonates and
      one 5-month-old foal were included. The most frequently observed clinical signs
      were alterations in mental status (10/10), recumbency (8/10), weakness (8/10),
      abnormal pupillary light reflexes (6/10), decreased suckling-reflex (6/9),
      seizures and/or nystagmus (4/10). Common clinicopathological alterations included
      hyperfibrinogenaemia (8/9), hyperlactataemia (7/7), and neutropenia (5/10) or
      neutrophilia (5/10). Most neonates (8/9) developed bacterial meningoencephalitis
      despite having a sepsis score near the cut-off value (median = 12). On CSF
      analysis, pleocytosis (9/9), increased total protein concentration (5/6) and
      intracellular bacteria (6/9) were detected. The most frequently isolated
      bacterium was Escherichia coil. Once bacterial meningoencephalitis was diagnosed,
      antimicrobial therapy was switched to third and fourth generation cephalosporins.
      CONCLUSIONS: The diagnosis of bacterial meningoencephalitis is established based
      on CSF analysis and culture. Clinical recognition of bacterial
      meningoencephalitis is difficult and can be easily overlooked. Moreover, severe
      sepsis is not necessary to develop bacterial meningoencephalitis. POTENTIAL
      RELEVANCE: CSF analysis should be considered more often in sick newborn foals
      with signs indicative of central nervous system (CNS) involvement. Cerebrospinal
      fluid (CSF) cytology and culture would help to confirm or rule out unnoticed
      bacterial meningoencephalitis, and to choose appropriate antimicrobial therapy

PMID- 22594037
TI  - Dysphagia associated with presumed pharyngeal dysfunction in 16 neonatal foals.
AB  - REASONS FOR PERFORMING STUDY: Dysphagia due to pharyngeal dysfunction occurs in
      human neonates and is associated with prematurity and hypoxic episodes. This
      syndrome probably occurs in neonatal foals but has not been reported. OBJECTIVES:
      The objectives of this study were to describe 1) a series of neonatal foals with
      dysphagia due to pharyngeal dysfunction; 2) the progression, treatment and
      resolution of the dysphagia; 3) the comorbidities; and 4) the prognosis for life
      and athleticism for affected foals. METHODS: Records from 3 referral equine
      hospitals were reviewed from neonatal foals with dysphagia of pharyngeal origin.
      Inclusion criteria were a normal to strong suckle, dysphagia evidenced by milk at
      the nostrils after nursing the dam, and endoscopic examination of the airway.
      Foals with mechanical reasons for dysphagia, botulism or hyperkalaemic periodic
      paralysis were not included. RESULTS: Sixteen neonatal foals qualified for the
      study. Eight (50%) were premature and/or diagnosed with hypoxic ischaemic
      encephalopathy. Twelve (75%) had aspiration pneumonia. Fifteen foals were
      discharged alive from the hospital, nursing the mare with no evidence of
      dysphagia (n = 14), or mild dysphagia (n = 1), a mean +/- s.d. of 7 +/- 6 days
      (median = 6.3 days, range 0-22 days) after hospital admission. One foal was
      subjectedto euthanasia in hospital. Follow-up nformation was available for 14
      animals. Thirteen of 16 (81%) were alive and included one yearling and 12 horses
      >2 years old. Seven of the 14 (50%) were racing, training or in work, and 6
      horses were pets, breeding animals or had unknown athletic status. Two had
      laryngeal deficits. One foal was subjected to euthanasia within weeks of
      discharge from the hospital due to aspiration pneumonia. CONCLUSION: Dysphagia
      related to pharyngeal dysfunction occurs in equine neonates and can resolve, but
      may require days to weeks of supportive care. Prognosis for life is favourable
      and for athleticism fair.

PMID- 22594038
TI  - Allopregnanolone infusion induced neurobehavioural alterations in a neonatal
      foal: is this a clue to the pathogenesis of neonatal maladjustment syndrome?
AB  - REASONS FOR PERFORMING THE STUDY: Increased plasma progestagen concentrations
      have been reported in foals with neonatal maladjustment syndrome (NMS). These
      steroids may cross the blood-brain barrier and have dampening effects in the
      central nervous system. OBJECTIVES: To evaluate if the infusion of a progesterone
      derivative (allopregnanolone) in a healthy neonatal foal would induce clinical
      signs compatible with NMS. METHODS: A healthy neonatal foal from a healthy mare
      with a normal gestation (length, no complications), birth and placenta was
      infused with allopregnanolone to observe its neurobehavioural effects.
      Heparinised blood samples were collected pre- and post infusion to determine
      various progestagen concentrations using liquid chromatography mass spectrometry.
      A second healthy neonatal foal was infused with ethanol and saline for comparison
      of clinical observations. RESULTS: Infusion of allopregnanolone resulted in
      obtundation, lack of affinity for the mare and decreased response to external
      stimuli. These effects were short-lasting and associated with measurable
      concentrations of progestagens. CONCLUSIONS AND POTENTIAL RELEVANCE: Infusion of
      a steroid metabolite to a healthy neonatal foal resulted in neurobehavioural
      alterations compatible with those observed in foals with NMS. These findings
      suggest that increased progestagen concentrations may be responsible for some of
      the behavioural changes observed in foals with NMS.

PMID- 22594039
TI  - Factors influencing placental development and function in the mare.
AB  - The development of the equine placenta involves a series of stage-specific events
      which ensure that the fetus is nourished throughout its 11 months of gestation.
      Initially, placental exchange to the developing embryo is histotrophic, via the
      yolk sac but, as the allantochorion develops and microcotyledons form,
      haemotrophic nutrition plays the major role in sustaining the increasing demands
      of the growing fetus. This review describes the development of the
      allantochorionic placenta of the mare and discusses some of the factors that
      influence its growth, size and functions and, hence, its control of fetal growth
      and maturation.

PMID- 22594040
TI  - A racing start in life? The hurdles of equine feto-placental pathology.
AB  - Significant progress has been made in understanding and monitoring the causes of
      equine abortion over past decades. However, not all in utero pathology results in
      abortion. It has long been recognised that some in utero pathology, such as
      twinning or chronic placentitis, can result in the birth of live but growth
      retarded foals and there is historical evidence that birth weight may influence
      future athletic performance. Clinical experience (e.g. from twins) and
      experimental studies (pony-Thoroughbred embryo transfer) have highlighted the
      importance of reduced functional placental area in limiting growth in utero in
      horses. Many other nonfatal in utero pathologies (e.g. umbilical cord-related
      circulatory compromise) can potentially affect either placental function or other
      organ systems. Their influence on the short- and long-term health of the foal and
      its future athletic performance is in many cases poorly documented or understood.
      This review summarises the main causes of in utero pathology and reflects on how
      these may potentially affect the foal if born alive, highlighting the need for
      long-term studies on this important subject.

PMID- 22594041
TI  - Endocrine adaptations in the foal over the perinatal period.
AB  - In adapting to life ex utero, the foal encounters a number of physiological
      challenges. It has to assume the nutritional, respiratory and excretory functions
      of the placenta and activate full regulatory control over its own internal
      environment for the first time. To achieve this, there must be structural and
      functional changes to a wide range of tissues including several endocrine glands.
      In most species, including the horse, these maturational changes begin in late
      gestation and continue into the first few days of neonatal life. Consequently,
      during this perinatal period, there are major changes in the sensitivity and/or
      set point of key endocrine axes, which alter the circulating hormone
      concentrations in the foal. In turn, these endocrine changes are responsible for
      many of the other physiological adaptations essential for neonatal survival. The
      perinatal alterations in the hypothalamic-pituitary-adrenal (HPA) axis are
      particularly important in these processes, although the sympatho-adrenal
      medullary axis and endocrine pancreas also have key roles in ensuring homeostasis
      during the multiple novel stimuli experienced at birth. Abnormalities in the
      perinatal endocrine profile caused by adverse conditions before or after birth
      may, therefore, lead to maladaptation or aid survival of the newborn foal
      depending on the specific circumstances. This review examines the perinatal
      changes in endocrinology in normal and compromised foals and the role of these
      endocrine changes in the physiological adaptations to extrauterine life with
      particular emphasis on the HPA axis, adreno-medullary catecholamines and the
      endocrine pancreas.

PMID- 22594042
TI  - Prostaglandins and the regulation of parturition in mares.
AB  - Prostaglandins play an essential role during the perinatal period in the mare.
      Prostaglandin concentrations are low for the majority of pregnancy due to the
      regulatory action of progestagens on those enzymes responsible for metabolism of
      prostaglandins. Towards term, prostaglandin concentrations gradually increase,
      closely associated with upregulation of the fetal hypothalamo-pituitary-adrenal
      axis, stimulation of the prostaglandin synthesising enzyme PGHS-2 and changes in
      the ratio of progestagens and oestrogens. Recent evidence in the mare indicates
      that proinflammatory cytokines are key mediators of prostaglandin synthesis both
      at term parturition in healthy mares and at preterm parturition associated with
      placental infection. Prostaglandin concentrations rise substantially during
      active labour and decline after birth, associated with delivery of the placenta.
      During induced labour, prostaglandin concentrations are variable depending on the
      proximity to spontaneous parturition at term. Once the proinflammatory endocrine
      cascade is initiated, it is difficult to prevent active labour by administration
      of drugs that reduce prostaglandin concentrations in peripheral plasma. Further
      work is needed to establish the inter-relationships between prostaglandin
      production and other endocrine changes associated with labour at term and preterm
      in the mare.

PMID- 22594043
TI  - Feeding the foal for immediate and long-term health.
AB  - The nutrition and nutritional status of the mare, as well as foal's nutrient
      intake from colostrum, milk and creep feed, are critical factors that are known
      to influence the growth period of the foal. Long-term effects of mare and foal
      nutrition are not well recognised or understood in the horse but may have the
      greatest impact on the animal's health and use when mature. Both under- and
      overfeeding can negatively influence important characteristics such as bone
      development and neurological function The risk of developing debilitating
      diseases such as metabolic syndrome may also be increased by mare, fetal and
      early foal feeding, supporting the importance of providing a balanced diet to
      mare and foal throughout gestation and beyond.

PMID- 22594044
TI  - The FREED Act.

PMID- 22594045
TI  - Practicing professionalism.

PMID- 22594046
TI  - Global initiatives in nursing.

PMID- 22594047
TI  - Nursing students with disabilities.

PMID- 22594048
TI  - NSNA alumni.

PMID- 22594049
TI  - The growth and development of professional nurses.

PMID- 22594050
TI  - Dodging the landmines in social media.

PMID- 22594051
TI  - Building relationships: how business-savvy communication can advance your nursing
      career.

PMID- 22594053
TI  - Delays, uncertainty, and waiting continue to dominate healthcare policy.

PMID- 22594052
TI  - Passing the torch of success: becoming a mentor-leader.

PMID- 22594054
TI  - Strategic planning to reduce medical errors: Part II--therapy.
AB  - In Part I of this series, medical errors were analyzed from a systems dynamics
      viewpoint. It was noted that despite extensive dialogue and a continuing stream
      of proposed medical practice revisions, medical errors and adverse impacts
      persist. Connectivity of vital elements is often underestimated or not fully
      understood. In Part II, our analysis suggests that the most fruitful strategies
      for dissolving medical errors include facilitating physician learning, educating
      patients about appropriate expectations surrounding treatment regimens, and
      creating "systematic" patient protections rather than depending on (nonexistent)
      perfect providers.

PMID- 22594055
TI  - Why are ACOs doomed for failure?
AB  - Among the more ambitious parts of the Patient Protection and Affordable Care Act
      (2010) is the formation of Accountable Care Organizations (ACOs) that offer
      fiscal rewards when well-organized, integrated hospital-physician groups can
      improve quality of care and reduce the cost of Medicare expenditures. After
      studying the conceptual and operational issues, it is concluded herein that ACOs
      are in the long-haul doomed for failure since: 1) most hospitals and physicians
      have major difficulties in consummating tightly coordinated collaborative
      efforts; 2) providers historically have had a dismal track record in reducing
      cost, because of existing fee-for-service incentives; and 3) existing regulations
      do not provide sufficient fiscal rewards to assume the cost of starting an ACO
      and its possible operational risks.

PMID- 22594056
TI  - Three payer strategies to increase revenue.
AB  - If medical practices use these three payer strategies, they will increase
      revenue. Analyzing each payer's performance and then comparing payers with each
      other will highlight those who are not performing well. You may also want to
      compare the experience you are having with a payer to the results from the
      American Medical Association's fourth annual National Health Insurer Report Card,
      which was released in June 2011.2 Medical practices need to increase payer
      specific knowledge among staff and physicians. One way is to analyze your denial
      data to create targeted training sessions for the practice's team. Finally,
      consider how new technologies, such as claim scrubbers, can automate and
      streamline the front-end claim-editing process, which will result in receiving
      payments faster and reducing your denial rate.

PMID- 22594057
TI  - First impressions and beyond: marketing your practice in touch points--Part II.
AB  - When calling in a marketing expert to boost a practice's numbers, administrators
      and providers are usually looking for external marketing strategies--ways to
      attract new patients to the practice. However, one of the most important, yet
      often overlooked, elements to successfully marketing a practice is the very
      important work of retaining current patients and turning them into enthusiastic
      referrers. When new patients are simply filling the place of previous patients
      that have moved on, you are not building solid practice growth. You can create an
      atmosphere of loyal referring patients by providing positive touch points that
      fulfill the needs of your patients. This article will cover touch points that
      occur before a patient has chosen your practice. Laying the groundwork for
      positive touch points will give your marketing efforts a snowball effect, build
      growth, and deliver the most bang for your marketing bucks.

PMID- 22594058
TI  - PHI faux pas: social media and the unauthorized disclosure of PHI.
AB  - The pervasiveness of social media in modern communication has created increased
      liability for healthcare providers when trying to safeguard patients' protected
      health information (PHI). This article addresses a few of the most basic but
      pervasive ways, including "friending," "tagging," and "blogging," that PHI is
      unthinkingly shared on social media platforms and the precautions that providers
      can take to avoid such unauthorized disclosures. It is recommended that
      healthcare providers: 1) require online "friends" to agree to a written
      disclosure before connecting; 2) avoid tagging or posting photos online that
      include images of patients; and 3) do not comment or write about a patient on any
      online platform or blog without written approval from the patient. Ultimately, it
      is imperative that healthcare providers implement and enforce detailed social
      networking policies and integrate those policies with their human resources
      disciplinary policies in order to guard against HIPAA violations.

PMID- 22594059
TI  - Physician practice mergers: what makes them succeed?

PMID- 22594060
TI  - How to get patients seen when they need it (or how we fought the matrix and won).
AB  - Before the recession, growth was easy. The environment was fairly predictable,
      and returns on investment came quickly. With little difficulty, a private
      practice could increase the total services it provided, resulting in increased
      patient encounters and increased profit. But the growth of Maryland's largest and
      oldest orthopaedic practice came with a price: a jumbled, imposing document known
      as "the matrix" that governed a troubled appointment process. OrthoMaryland knew
      the matrix had to go but lacked an incentive to do the work needed to replace it.
      Then came the recession, which made borrowing money for a private specialty
      practice like OrthoMaryland as difficult as borrowing money for a home loan. At
      the same time, the Patient Protection and Affordable Care Act is transforming the
      way private practices will be reimbursed for services. The changes to the fee-for
      service model plus the increased emphasis on patient satisfaction meant the
      practice would need to both increase the number of patients seen and make them
      more satisfied at the same time. And that meant the matrix had to go.

PMID- 22594061
TI  - Instructional objectives focus your training--and your management--efforts.

PMID- 22594062
TI  - Evidence-based management.
AB  - It's OK to be lucky when you're lucky, but it's not OK when the issues are
      critical. Too often, we manage by anecdote, which is OK when you can afford to be
      wrong, but when finances are tight, or the market is overregulated, or a lot is
      at stake, making mistakes is not an option. Evidence-based management depends on
      attention to three components: analytics, decision making, and problem solving.
      These are skills that should be required of everyone who assumes a management
      position, no matter how high or low one is on the totem pole. Understanding basic
      analytical techniques, knowing how to apply these techniques to making good
      decisions, and learning how to become a skilled problem solver ensure that, when
      we manage our businesses, we minimize the risk of mistakes and maximize the
      potential for positive outcomes.

PMID- 22594063
TI  - The potholed path to becoming a physician executive.
AB  - This article discusses evolving career pathways for physician executives-
      pathways that take physicians out of primarily patient care roles and into
      management activities. The discussion is textured with "how-to" advice for
      readers who may have aspirations of becoming physician managers and executives.
      The advice stems from my own experiences in the pharmaceutical industry and other
      healthcare sectors. Specific topics addressed include: attending business school,
      gaining management experience, working in large corporations, dealing with job
      loss, acquiring both hard and soft skills, cultivating mentors, and developing
      leadership competencies. Physician executives must demonstrate strong leadership
      abilities and learn how to tactfully confront difficult people and problems.

PMID- 22594064
TI  - What the medical practice employee needs to know about workplace bullying.
AB  - An eye roll, a glare, a dismissive snort, a nasty remark, a joke at someone's
      expense--these are some of the subtle tactics of the workplace bully. Such
      behaviors may not sound like much by themselves. However, that is precisely why
      they are so insidious and why workplace bullying is so much more common than many
      people realize. This article will help medical practice employees and
      administrators learn the skills and techniques they need to identify workplace
      bullying and to neutralize and overcome bullying behaviors when they encounter
      them. It describes what workplace bullying is and isn't, and offers startling
      statistics about the scope of the workplace bullying problem today. This article
      also describes the characteristics of workplace bullies and their targets, and
      how bullying affects both the targeted individual and the employer. It offers
      eight strategies for the medical practice manager to prevent and deal effectively
      with bullying. It also offers 12 tips for employees who are the target of
      bullying and additional strategies to help and guide bullying bystanders.
      Finally, this article offers 10 additional strategies for preventing and dealing
      with workplace bullying, a checklist of bullying behaviors, and a sample medical
      practice anti-bullying policy.

PMID- 22594065
TI  - Influencing hospitalist clinical productivity with feedback.
AB  - Periodic clinical productivity feedback with peer comparison produces significant
      changes to CPT code distributions, which leads to improvements in per-encounter
      work relative value units (wRVUs) (+25%) and charges (+20%). Improved wRVU
      production and charges can lead to increased collections, thus improving a
      practice's financial outlook without increasing patient volume. These
      interventions have minimal cost or risk to a hospitalist practice.

PMID- 22594066
TI  - Twelve points leading to improvement of patient collections.

PMID- 22594067
TI  - Lessons learned from the Apple stores.
AB  - Medical practices have an opportunity to improve the services that they offer
      their patients. Practices can look at other businesses and industries for
      examples of outstanding customer service. This article will discuss the services
      provided by Apple, Inc., and how medical practices can learn from this industry
      giant and improve the services that they offer patients.

PMID- 22594068
TI  - The forgotten players in ACO development: nursing homes.
AB  - Given the history and dynamics of the Patient Protection and Affordable Care Act,
      nursing homes have been left out of the business of Accountable Care Organization
      (ACO) development and implementation over the last year. Only now are ACOs,
      hospitals, and physicians realizing that an effective ACO needs long-term care
      and rehabilitation as a key component to maximize shared savings in the ACO
      environment. This article discusses the history of ACO development, examines why
      nursing homes may have been left out, and explains why nursing homes are critical
      participants in ACO effectiveness. The article also discusses how nursing homes
      will need to position their businesses for ACO participation.

PMID- 22594069
TI  - Health reform and retirement plan investment advice developments.

PMID- 22594070
TI  - Medical leasing.
AB  - Leases for medical space can have far-reaching (and sometimes unintentional)
      consequences for the future of the practice and the costs of the business. In
      order to prevent hardship and expense down the line, it is especially important
      to review the lease to make sure that it reflects the practice's goals, needs,
      and structure. This article provides a number of provisions that are especially
      crucial to review and negotiate when leasing medical space, including use
      restrictions, assignment and subleasing clauses, build-out terms, and legal
      compliance requirements.

PMID- 22594071
TI  - Public speaking for the healthcare professional: Part III--after the program.
AB  - Public speaking is one of life's greatest fears for many people. However, with
      practice, repetition, and planning, you can safely leave your comfort zone and
      make a presentation that will engage the members of the audience, attract their
      attention, and cause them to take action on your material. This third article in
      the series will discuss what to do after the last slide is shown.

PMID- 22594072
TI  - Computer briefs: the healthcare cloud.

PMID- 22594073
TI  - 2012 legisative, regulatory and hospice priorities.

PMID- 22594074
TI  - Supreme Court to hear health care reform lawsuits.

PMID- 22594075
TI  - Don't let our country make a long-term mistake.
AB  - The CLASS Act (Community Living Assistance Senrvices and Support Act) represented
      a vision --a vision of a system of services that was owned and invested in by the
      citizens of the United States. CLASS is intended to be an infrastructure under
      which the government would design a voluntary, federally administered, consumer
      financed insurance plan. It became law when President Barack Obama signed the
      Patient Protection and Affordable Care Act on March 23, 2010. The CLASS plan
      would provide those who participate with cash to help pay for needed assistance
      if they become functionally limited. This cash benefit is intended to be used in
      the place people call home, ranging from independent living to a nursing
      facility, if they so choose. While most provisions of the CLASS Act became
      effective as of January 1, 2011, it was up to the secretary of Health and Human
      Services (HHS) to develop the details of the plan and proceed to its
      implementation. The law requires that the secretary release details of the plan
      no later than October 1, 2012.

PMID- 22594076
TI  - Spinning health care: the Republican presidential candidates.

PMID- 22594077
TI  - Realizing the dream for private duty home care.

PMID- 22594078
TI  - Grief relief: looking for laughter in loss.

PMID- 22594079
TI  - Increasing the probability of success.

PMID- 22594080
TI  - A chance for healing.

PMID- 22594081
TI  - Unrelenting screaming in someone with Alzheimer's: what causes it?

PMID- 22594082
TI  - A capital agenda on Capitol Hill.

PMID- 22594083
TI  - Smartphones, tablets in the OR: with benefits come distractions.

PMID- 22594084
TI  - Social media: helping staff manage personal, professional boundaries.

PMID- 22594085
TI  - Reconnecting OR managers with their purpose.

PMID- 22594086
TI  - A new 'electronic etiquette' for surgical services.

PMID- 22594087
TI  - Evaluating surgical instrument repair options.

PMID- 22594088
TI  - Tips on making the most of instrument repair.

PMID- 22594089
TI  - New imaging modalities raise the bar for safety.

PMID- 22594090
TI  - A clearer, more robust surgical consent process.

PMID- 22594091
TI  - Joint Commission's top ten toughest standards.

PMID- 22594092
TI  - Joint Commission tools to prevent wrong surgery.

PMID- 22594093
TI  - Quality council aids ASC staff in building skills.

PMID- 22594094
TI  - Integrated traditional and Western medicine for treatment of depression based on
      syndrome differentiation: a meta-analysis of randomized controlled trials based
      on the Hamilton depression scale.
AB  - OBJECTIVE: To systematically review the benefits of integrated traditional and
      Western medicine therapies based on the Hamilton depression scale (HAMD)
      following syndrome differentiation of depression. METHODS: We searched six
      English and Chinese electronic databases for randomized clinical trials (RCTs) on
      integrated traditional and Western medicine for treatment of depression. Two
      authors extracted data and independently assessed the trial quality. RevMan 5
      software was used for data analyses with an effect estimate presented as weighted
      mean difference (WMD) with a 95% confidence interval (CI). RESULTS: Seven RCTs
      with 576 participants were identified for this review. All trials were eligible
      for the meta-analysis and were evaluated as unclear or having a risk of bias.
      Meta-analysis showed, compared with Western medicine alone, integrated
      traditional and Western medicine based on syndrome differentiation could improve
      the effect of treatment represented by the HAMD [WMD = -2.39, CI (-2.96,-1.83), Z
      = 8.29, P < 0.00001]. There were no reported serious adverse effects that were
      related to integrated traditional and Western medicine based therapies in these
      trials. CONCLUSIONS: Integrated traditional and Western medicine based therapies
      for the syndrome differentiation of depression significantly improved the HAMD,
      illustrating that combining therapies from integrated traditional and Western
      medicine for treatment of depression is better than Western medicine alone.
      However, further large, rigorously designed trials are warranted due to the
      insufficient methodological rigor seen in the trials included in this study.

PMID- 22594095
TI  - Meta analysis of the curative effect of acupuncture on post-stroke depression.
AB  - OBJECTIVE: To systematically evaluate the curative effect of acupuncture on post
      stroke depression (PSD). METHODS: The internet was used to retrieve the Wanfang
      Medical Data System, Chinese Periodical Net, the Weipu Information Resources
      System, PubMed and the Cochrane Library Database. Relevant articles, up to
      September 2010, were manually retrieved. These papers included studies that had
      performed random and semi-random control trials for the use of acupuncture to
      treat PSD. Fifteen random control tests involving 1096 patients were included in
      this study and individual cases, interventional measures and curative effects
      were extracted from this research. Grade methodological quality evaluation and
      meta-analysis were performed on these studies. RESULTS: Comparison between the
      acupuncture group and the Western medicine group for the curative rate on PSD
      revealed an OR of 1.48, 95% CI = [1.11 1.97] and P = 0.008. Comparison of
      obviously effective rate shows that OR = 1.39, 95% CI = [1.08 1.80] and P = 0.01.
      Comparison of effective rate shows that OR = 0.83, 95% CI = [0.631.09] and P =
      0.18. CONCLUSION: Comparison between the acupuncture group and Western medicine
      group in treating PSD revealed that there is a statistical difference in curative
      rate and remarkably effective rate, but no difference in effective rate.

PMID- 22594096
TI  - Systematic review of randomized controlled trials of traditional Chinese medicine
      treatment of non-acute bronchial asthma complicated by gastroesophageal reflux.
AB  - OBJECTIVE: To assess the effectiveness and safety of Traditional Chinese Medicine
      (TCM) treatment of non-acute bronchial asthma complicated by gastroesophageal
      reflux. METHODS: We searched databases from MEDLINE, Cochrane Library, CNKI, VIP,
      CBM, Wanfang Data, and TCM Database Systems. All randomized, controlled trials
      (RTCs) of TCM treatment of non-acute asthma complicated by gastroesophageal
      reflux were included. Data were independently collected by two reviewers. The
      standards for assessing quality described in the Cochrane Handbook for Systematic
      Reviews of Interventions were used to evaluate articles. Meta-analyses were
      conducted using Rev- Man 5.0.17 software. Heterogeneity was assessed, and a
      corresponding effects model was used to merge and analyze results. Indexes used
      to evaluate curative effects were: clinical efficacy, symptom scores, pulmonary
      function values, and adverse incidents. Effectiveness was indicated using risk
      ratio (RR) or mean difference (MD), and 95% confidence intervals (CIs) were
      calculated. RESULTS: Six RCTs were included, involving 304 patients with non
      acute asthma complicated by gastroesophageal reflux. The treatment groups
      received Chinese drugs alone or TCM combined with standard Western medical
      treatment, and the control groups received standard Western medical treatment
      alone. Standard Western medical treatment included anti-inflammatory drugs and
      bronchodilators for asthma, and drugs to promote gastric peristalsis and inhibit
      gastric acid production for gastroesophageal reflux. Methodological quality was
      low in all six RCTs. Two RCTs showed that clinical efficacy was higher in the
      treatment group than in the control group (RR: 1.43, 95%CI: 1.10 to 1.87 vs RR:
      1.51, 95% CI: 1.09 to 2.08). One RCT showed that the asthma score was lowered
      more effectively in the treatment group than in the control group (MD:-1.10, 95%
      CI:-2.04 to-0.16). Two RCTs showed that the gastroesophageal reflux score was
      reduced more effectively in the treatment group than in the control group (RR:
      3.70, 95% CI:-4.30 to 3.10 vs RR:-5.30, 95% CI:-6.32 to -4.28). One RCT showed
      that some pulmonary function values were improved more effectively in the
      treatment group than in the control group (P < 0.05). No differences were seen in
      the various indexes between groups in the other RCTs. No adverse reactions,
      dropout rates, or follow-up rates were reported in any of the RCTs. CONCLUSIONS:
      The clinical symptoms of non-acute asthma complicated by gastroesophageal reflux
      can be improved by some Chinese drugs. Curative effects can be increased by
      combining the use of TCM with Western medicine. Because of the small quantity and
      low quality of research reported to date, it is necessary to conduct further RCTs
      to confirm these results. The results of this systematic review indicate that the
      quality of future clinical trials should be improved by including larger patient
      numbers, correctly randomizing patients into study groups, using blinding methods
      to measure and assess outcomes, and using accepted indexes to evaluate curative
      effects.

PMID- 22594097
TI  - Mechanisms, clinically curative effects, and antifungal activities of cinnamon
      oil and pogostemon oil complex against three species of Candida.
AB  - The anti-fungus mechanisms and curative effects of cinnamon oil and pogostemon
      oil complexes towards intestinal Candida infections were investigated. We
      measured the minimal inhibitory concentration (MIC) values of the complexes
      against Candida using proportionally-diluted test-tube medium, and examined the
      evolution of the morphology and structures of Candida albicans using scanning
      electronic microscopy (SEM) and transmission electronic microscopy (TEM). We
      found that the average MIC values of the complexes against the fungi were 0.064
      mg/mL (cinnamon oil), 0.032 mg/mL (pogostemon oil) for Candida albicans, 0.129
      mg/ mL (cinnamon oil), 0.064 mg/mL (pogostemon oil) for Candida tropicalis, and
      0.129 mg/mL (cinnamon oil), 0.064 mg/mL (pogostemon oil), for Candida krusei. SEM
      examination over a 24-48 h period showed that the morphology of Candida albicans
      cells changed significantly. Irregular hollows appeared on the surfaces, inside
      organelles were destroyed and the cells burst after treatment. TEM examination
      over a 48 - 72 h period indicated that the cell walls were damaged, organelles
      were destroyed and most cytoplasms became empty bubbles. Sixty intestinal Candida
      infected patients were treated with a capsule containing cinnamon and pogostemon
      oil. The curative ratio was 71.67% (43/60), and the improvement ratio was 28.33%
      (17/ 60), giving a total ratio of 100%. Thus, the cinnamon oil and pogostemon oil
      complexes had strong anti-fungus effects against Candida albicans, Candida
      tropicalis, and Candida krusei. They impacted the morphology and sub-micro
      structures of the fungus within 48 - 72 h, and eventually denatured and killed
      the cells. The complexes have also shown considerable curative effects to
      intestinal Candida infections.

PMID- 22594098
TI  - Therapeutic effects of acupuncture for neurogenic dysphagia--a randomized
      controlled trial.
AB  - OBJECTIVE: To evaluate the therapeutic effects and long-term efficacy of
      acupuncture for neurogenic dysphagia. METHODS: Subjects with neurogenic dysphagia
      undergoing routine swallowing management were randomized to receive either 20
      sessions of true acupuncture (experimental group) or sham acupuncture (control
      group 1) for approximately one and a half months. A third group (control group 2)
      comprised of non-randomized subjects with neurogenic dysphagia who received
      routine care were recruited from separate wards. The outcomes were assessed by
      the Royal Brisbane Hospital Outcome Measure for Swallowing (RBHOMS), as well as
      by the consistencies of ingested food and fluid. RESULTS: A total of 87 subjects
      (experimental group, n = 20; control group 1, n = 19; control group 2, n = 48)
      were recruited into the trial. The average RBHOMS score showed a greater
      improvement in the experimental group and in control group 1 than in control
      group 2. The average levels of food and fluid consistencies displayed greater
      improvement in the experimental group than in the two control groups.
      CONCLUSIONS: This study demonstrates that acupuncture may have therapeutic
      effects and long-term efficacy for neurogenic dysphagia. However, due to an
      insufficient sample size and the lack of follow-up for control group 2, multi
      centre trials employing a larger sample size may be required to draw concrete
      conclusions.

PMID- 22594099
TI  - Clinical research of acupoint application for "treatment of winter disease in
      summer" used to prevent and treat bronchial asthma in children.
AB  - OBJECTIVE: To preliminarily analyze key factors influencing curative effect
      through clinical observations of acupoint application for "treatment of winter
      disease in summer" used to prevent and treat bronchial asthma in children.
      METHODS: In an observational study and prospective cohort study, we observed
      children in remission of asthma at three class III grade A TCM hospitals in
      Liaoning, Hubei, and Chengdu. RESULTS: A total of 609 children conformed to
      diagnostic and inclusive standards for remission of bronchial asthma. Through
      follow-up visits, we observed their skin reactions and the time and chance of
      treatment with different therapies in the three hospitals; we also compared and
      analyzed different drugs, acupoints, and preparations. We found that the key
      Chinese drugs were Bai Jie Zi (Semen Sinapis Albae) and Yian Hu Suo (Rhizoma
      Corydalis); the key acupoints were Feishu (BL 13), Gaohuang (BL 43), Dingchuan
      (EX-B1), Tiantu (CV 22), and Shanzhong (CV 17); and the best preparation was a
      mixture of drugs, ginger juice, and musk. Acupoint application was practiced on
      the hottest days of summer and the coldest days of winter for 0.5 to 2 h with the
      lowest rate of asthma relapse. CONCLUSIONS: The present data analysis shows that
      the curative effect of acupoint application for "treatment of winter disease in
      summer" may be influenced by recipes of Chinese drugs, preparations,
      prescriptions of acupoints, chance, time, and skin reactions. A curative effect
      is the result of the comprehensive action of these factors.

PMID- 22594100
TI  - The influence of different methods of acupuncture on skin surface perfusion.
AB  - OBJECTIVE: To compare the effects on the body surface of different kinds of
      placebo/sham acupuncture with that of traditional needling sensation acupuncture.
      METHODS: Point Neiguan (PC 6) of 29 healthy subjects, 19 males and 10 females,
      was stimulated with needling sensation, shallow, placebo and deep acupuncture at
      the non-acupoint. After stimulation with different methods of acupuncture, the
      change in perfusion of the micrangium in the skin surface around the elbow joint,
      with Point Quze (PC 3) as its center, was observed with laser Doppler blood-flow
      imaging. RESULTS: Judging from the absolute value of perfusion of the skin
      surface micrangium, several methods of acupuncture can cause change in blood
      flow. The ratio of blood-flow perfusion in the meridian area in and around Quze
      declined before and after needling insertion in needling sensation acupuncture
      and shallow acupuncture. This observation did not occur in placebo and non
      acupoint acupuncture. Needling sensation acupuncture at an acupoint can
      relatively reduce the perfusion of the micrangium in the projective area of the
      meridian where the acupoint is located on the body surface (P < 0.05), indicating
      the specificity of meridians. CONCLUSIONS: Stimulation of an acupoint or a point
      on the body surface with any type of acupuncture can cause change in blood flow
      in the skin near the needling point. However, the biological mechanism underlying
      this phenomenon needs to be further explored.

PMID- 22594101
TI  - Effects of mild-warming moxibustion on Bcl-2 and PKC expressions of peripheral
      blood in elderly people.
AB  - OBJECTIVE: To explore the anti-aging effects of mild-warming moxibustion on Bcl-2
      and PKC expression in peripheral blood and general symptoms in elderly people.
      METHODS: A total of 61 elderly people and 30 non-elderly people were enrolled.
      The total effective rate of mild-warming moxibustion was assessed by symptom
      scores, and Bcl-2 and PKC expression in peripheral blood was detected by flow
      cytometry. RESULTS: The total effective rate in the mild-warming moxibustion
      group was significantly higher than in the blank control group (P < 0.01). Bcl-2
      and PKC expression rates in peripheral blood in the blank control group were
      lower than in the normal control group (< 0.01), but higher after mild-warming
      moxibustion (P < 0.01). CONCLUSION: The anti-aging effects of mild-warming
      moxibustion may be due to increased Bcl-2 and PKC expression in peripheral blood
      in aged people.

PMID- 22594102
TI  - Effects of Wei Chang An pill on enzyme activity and levels of vasoactive peptide
      and substance P in the small intestine of rats with compound diarrhea.
AB  - OBJECTIVE: To investigate the regulatory effects of Wei Chang An Pill (WCAP) on
      enzyme activity and gastrointestinal hormones in the small intestine of rats with
      compound diarrhea. METHODS: Forty Wistar rats were randomly divided into a
      control, diarrhea model, and WCAP high, medium, and low dose groups. The control
      group was not treated, and the model group was administered intragastric
      distilled water. The WCAP groups were given WCAP suspension, 80, 60 or 40 mg x
      kg(-1) x d(-1), for 4 days. Stool properties were observed. After the experiment,
      thymus and spleen indices were measured, and the activities of lactate
      dehydrogenase (LDH), malate dehydrogenase (MDH), and disaccharidase (lactase) in
      the small intestinal mucous membrane, and levels of substance P (SP) and
      vasoactive peptide (VIP) in the colon were determined. RESULTS: Compared with the
      control group, thymus and spleen indices were significantly decreased, LDH, MDH,
      and disaccharidase activity in the small intestine was decreased, and SP and VIP
      levels in the colon were significantly increased in the diarrhea model group.
      Compared with the model group, thymus and spleen indices were significantly
      increased, and LDH, MDH, and disaccharidase activity in the small intestine and
      SP and VIP levels in the colon were significantly decreased in the WCAP medium
      dose group. CONCLUSION: The diarrhea model rats exhibited pathological changes
      including atrophy of the thymus and spleen, decreased enzyme activity in the
      small intestine, and gastrointestinal hormone disturbance. WCAP can increase the
      activity of intestinal digestive enzymes and regulate gastrointestinal hormones,
      thereby relieving diarrhea.

PMID- 22594103
TI  - Effect of houttuynia cordata aetherolea on adiponectin and connective tissue
      growth factor in a rat model of diabetes mellitus.
AB  - OBJECTIVE: To determine the effect of Houttuynia cordata Aetherolea on connective
      tissue growth factor and adiponectin in a rat model of diabetes mellitus (DM).
      METHODS: DM was induced in rats using streptozotocin (STZ) and high glucose-lipid
      animal feed. Animals were then treated with Houttuynia cordata Aetherolea for 8
      weeks. Changes in connective tissue growth factor and adiponectin levels in rats
      were observed. RESULTS: Connective tissue growth factor and adiponectin levels in
      rats with DM improved after Houttuynia cordata Aetherolea treatment. CONCLUSION:
      Houttuynia cordata Aetherolea had a positive effect on rats with DM by reducing
      levels of connective tissue growth factor and increasing adiponectin levels.

PMID- 22594104
TI  - Effects of compound danshen tablets on spatial cognition and expression of brain
      beta-amyloid precursor protein in a rat model of Alzheimer's disease.
AB  - OBJECTIVE: To observe the effects of Compound Danshen Tablets (CDST) on spatial
      cognition and expression of brain b-amyloid precursor protein (beta-APP) in a rat
      model of Alzheimer's disease. METHODS: The rat model of Alzheimer's disease (AD)
      was established using D-galactose to cause subacute aging combined with Meynert
      nucleus damage. Rat behavior was monitored using the Morris water maze, and the
      expression of beta-APP in rat brain tissue was detected via immunohistochemistry.
      RESULTS: CDST significantly improved spatial cognition and decreased beta-APP
      expression in the cortex and hippocampus (P < 0.05, P < 0.01). CONCLUSIONS: CDST
      can significantly improve spatial cognition in a rat model of AD. This
      observation is possibly related to a reduction in beta-APP expression in the rat
      brain.

PMID- 22594105
TI  - Effects of bushen huoxue yin on brain NF-kB and NO content in the Parkinson's
      disease model mouse.
AB  - OBJECTIVE: To observe the effects of Bushen Huoxue Yin on nuclear transcription
      factor kappa B (NF-KB) and nitric oxide (NO) in the brain of the Parkinson's
      disease (PD) model mouse. METHODS: Forty-five C57BL/6 mice were randomly divided
      into three groups; normal, model and BSHXY treatment groups. Concentrations of NF
      KB and NO in mouse brain tissue were determined by ELISA and spectrophotometry,
      respectively. RESULTS: NF-KB concentration in brain tissue in the model group was
      14.04 +/- 4.38 microg x L(-1), which was higher than that in normal (P < 0.01)
      and BSHXY (P < 0.05) groups. NO content in brain tissue in the model group was
      5.93 +/- 0.79 micromol x gprot(-1), which was also higher than that in model (P <
      0.01) and BSHXY (P < 0.01) groups. However, there were no significant differences
      in the content of NF-KB and NO between BSHXY and normal groups (P > 0.05).
      CONCLUSION: The mechanism of BSHXY for treatment of PD is possibly related to
      inhibition of NF-KB activation and decreased NO content in the brain.

PMID- 22594106
TI  - Effects of xuesetong soft capsules on angiogenesis and VEGF mRNA expression in
      ischemic myocardium in rats with myocardial infarction.
AB  - OBJECTIVE: To observe the effects of Xuesetong Soft Capsules, Notoginseng total
      saponin) on angiogenesis and vascular endothelial growth factor (VEGF) mRNA
      expression in ischemic myocardium of rats with myocardial infarction. METHODS:
      The left coronary artery of rats was ligated to establish the animal model of
      acute myocardial infarction. Rats were randomly divided into Xuesetong Soft
      Capsule, Shexiangbaoxin Pill (positive control), model (negative control) and
      sham operation groups. After 6 weeks, microvessel count (MVC), microvessel
      density (MVD) and VEGF mRNA expression in ischemic myocardium were evaluated.
      RESULTS: MVC and MVD in the myocardial infarct border area in model,
      Shexiangbaoxin Pill and Xuesetong Soft Capsule groups significantly increased
      compared with those of the sham operation group (P < 0.05). MVC and MVD in the
      myocardial infarct border area in Xuesetong Soft Capsule and Shexiangbaoxin Pill
      groups significantly increased compared with those of the model group (P < 0.05).
      No significant differences between Xuesetong Soft Capsule and Shexiangbaoxin Pill
      groups were observed (P > 0.05). The model group showed significantly higher VEGF
      mRNA expression than that in the sham operation group (P < 0.05). Xuesetong Soft
      Capsule and Shexiangbaoxin Pill groups showed significantly higher VEGF mRNA
      expression than that of the model group (P < 0.05). No significant difference
      between Xuesetong Soft Capsule and the Shexiangbaoxin Pill groups was observed (P
      > 0.05). CONCLUSION: Xuesetong Soft Capsules promote angiogenesis in ischemic
      myocardium after myocardial infarction and the mechanism may be associated with
      VEGF mRNA expression.

PMID- 22594107
TI  - An experimental study of a modified dahuang zhechong pill on the--angiogenesis of
      RF/6A cells in vitro.
AB  - OBJECTIVE: To investigate the effects of a modified Dahuang Zhechong Pill (MDZP)
      on the angiogenesis of rhesus choroid-retina endothelial (RF/6A) cells and its
      preliminary mechanism. METHODS: A 3-(4, 5-dimethylthiazol-2-yl)-5-(3
      carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) method was used to
      assess the effect of a MDZP on RF/6A cell proliferation induced by vascular
      endothelial growth factor (VEGF). Transwell inserts were used to assess the
      effect of the MDZP on RF/6A cell migration. Matrigel was used to assess the
      effect of the MDZP on the tube formation of RF/ 6A cells. Western blotting and
      quantitative real-time reverse transcription polymerase chain reaction (RT-PCR)
      were used to detect the protein and mRNA expression, respectively, of VEGF and
      matrix metalloproteinase-2 (MMP-2) in RF/6A cells treated with the MDZP. RESULTS:
      RF/6A cell proliferation induced by VEGF was inhibited by 0.2 mg/mL MDZP. At 0,
      12.5, 25 and 50 mg/mL MDZP, the number of cells that migrated through Transwell
      membranes was 73.33 +/- 4.51, 61.33 +/- 4.04, 28.67 +/- 6.66 and 17.67 +/- 4.16,
      respectively, and the number of tubes formed in Matrigel was 20.33 +/- 0.58,
      13.33 +/- 1.53, 11.00 +/- 1.00 and 1.33 +/- 0.58, respectively. At 100 and 200
      mg/mL MDZP, the protein and mRNA expression of VEGF and MMP-2 were inhibited in
      RF/6A cells. At 400 mg/mL MDZP, the expression of VEGF mRNA and MMP-2 protein
      were inhibited in RF/6A cells. CONCLUSIONS: MDZP inhibits the angiogenesis of
      RF/6A cells via the suppression of proliferation, migration and tube formation of
      RF/6A cells. Inhibition of the protein and mRNA expression of VEGF and MMP-2 in
      RF/6A cells may be an important mechanism.

PMID- 22594108
TI  - Study on effects of zhi zi (fructus gardeniae) on non-alcoholic fatty liver
      disease in the rat.
AB  - OBJECTIVE: To investigate the effects of Zhi Zi (Fructus Gardeniae) on non
      alcoholic fatty liver disease (NAFLD) induced by a high-fat diet in the rat.
      METHODS: A rat model of NAFLD was established using a high-fat diet. Twenty one
      rats were randomly divided into a normal group, a model group and a Zhi Zi
      treatment group, 7 rats per group. Drinking water and the drug were
      intragastrically administrated for 5 weeks. Samples were then taken to observe
      pathological changes of the liver tissue (HE staining); changes in the fat
      metabolism pathway e. g. triglyceride (TG) and free fatty acid (FFA) content;
      alterations in liver function, i.e. serum alanine aminotransferase (ALT) and
      aspartate aminotransferase (AST) activity; and differences in tumor necrosis
      factor alpha (TNF-alpha) and P-IkB protein expression in the liver tissue.
      RESULTS: Fatty degeneration and vacuole-like changes of different degrees
      occurred in hepatic cells of the model group. Markers for fat metabolism, serum
      ALT and AST activities, and expression of TNF-alpha and P-IkB proteins in liver
      tissue significantly increased. Fat metabolism in the Zhi Zi group significantly
      reduced, as shown by a drop in marker levels. Serum ALT and AST activities, and
      expression of TNF-alpha, P-IkB proteins in liver tissue were also significantly
      decreased in this group. CONCLUSION: Zhi Zi has a very strong inhibitory action
      on lipidosis and inflammatory injury in the rat model of NAFLD. This mechanism
      may possibly be related to the inhibition of the free fatty acid metabolism
      pathway.

PMID- 22594109
TI  - Combinatorial effects of naomai yihao capsules and vascular endothelial growth
      factor gene-transfected bone marrow mesenchymal stem cells on angiogenesis in
      cerebral ischemic tissues in rats.
AB  - OBJECTIVE: To investigate the combinatorial effects of Naomai Yihao (NMYH)
      Capsules and vascular endothelial growth factor (VEGF) gene-transfected bone
      marrow mesenchymal stem cells (BMSCs) on angiogenesis in cerebral ischemic
      tissues in rats and the mechanism. METHOD: BMSCs were isolated and cultured from
      bone marrow by an adherence method. Then, BMSCs were transfected with the
      eukaryotic expression plasmid pEGFP-VEGF165 by positive ionic liposome
      transfection. A rat model of middle cerebral artery occlusion (MCAO) was
      established. Rats were allocated to six groups: model, BMSC, VEGF gene
      transfected BMSC transplantation (BMSC/VEGF), NMYH, combined NMYH and BMSC/VEGF
      (combined treatment group) and sham operation groups. The behavioral rating score
      (BRS) of rats and the expression of CD34 and VEGF in brain tissue were measured
      by immunohistochemistry on days 7, 14 and 21 after reperfusion. Angiogenesis was
      observed and evaluated with laser scanning confocal microscopy. RESULTS: The BRS
      of rats in NMYH, BMSC transplantation and combined treatment groups was
      significantly lower than that of the model group (P < 0.001), with no significant
      difference between NMYH and transplantation groups (P = 0.619). The expression of
      CD34 and VEGF in NMYH, transplantation and combined treatment groups increased (P
      < 0.001), with a significant difference between NMYH and transplantation groups
      (P < 0.001). The blood vessel area in NMYH, transplantation and combined
      treatment groups was significantly increased (P < 0.05), without a significant
      difference between NMYH and transplantation groups (P = 0.873). CONCLUSIONS: VEGF
      gene-transfected BMSCs improve angiogenesis in the cerebral ischemic area. NMYH
      Capsules promote angiogenesis in MCAO rats treated with BMSC transplantation,
      which show an improved BRS. The mechanism of angiogenesis may be related to up
      regulation of VEGF expression.

PMID- 22594110
TI  - Comparison of the effects of carbamyl-beta-methylcholine chloride administered by
      intravenous, intramuscular and intra-acupuncture point injections.
AB  - OBJECTIVE: To compare the effects of carbamyl-beta-methylcholine chloride (CMCC)
      administered by intra-acupuncture point injection (IAI), intramuscular injection
      (IMI), and intravenous injection (IVI), and to analyze the mechanisms. METHODS:
      In the IAI group, CMCC was injected into the Zusanli acupoint (ST 36) immediately
      after 30-min stimulation by electro-acupuncture (EA) at the acupoints, and into
      the femoral vein and skeletal muscle in IVI and IMI groups, respectively. Intra
      gastric pressure was detected. The plasma concentration of CMCC was measured at
      various times. RESULTS: The gastric effect of CMCC in the IVI group was enhanced
      and attenuated more rapidly than in the other groups. In the IAI group, this
      effect was significantly stronger than that in the IMI group at 2 min and 15 min,
      but not significantly different between the two groups at 5 min and 30 min.
      Plasma concentration of CMCC in the IAI group was similar to that in the IVI
      group at 2 min, but higher than that in the IMI group. The concentration in the
      IAI group was higher than that in the IV group and similar to that in the IMI
      group at 5, 15 and 30 min, indicating rapid increase and slower reduction of the
      plasma concentration of the drug in the IAI group. There was a positive
      correlation between the plasma concentration of CMCC and intragastric pressure in
      all groups. CONCLUSION: The effect of IAI with CMCC was stronger than that of IMI
      and longer-lasting than that of IVI, which correlated with the blood
      concentration of CMCC.

PMID- 22594111
TI  - Effects of different frequencies of electro-acupuncture at shuigou (GV 26) on
      recovery of motor function in rats with focal cerebral ischemic injury.
AB  - OBJECTIVE: To investigate the effects of different frequencies of electro
      acupuncture at Shuigou (GV 26) on the latent period and wave amplitude of motor
      evoked potentials (MEPs) in rats with focal cerebral infarction. METHODS: Fifty
      healthy male Wistar rats were randomly divided into five groups: controls, model,
      2 Hz Shuigou, 50 Hz Shuigou and 100 Hz Shuigou. There were 10 rats in each group.
      Using a modification of a technique for middle cerebral artery occlusion, focal
      cerebral ischemic injury was induced in all rats except those in the control
      group. The rats in the control group received no treatment. After behavioral
      deficit had been evaluated using the Zausinger 6-point neurological function
      score, the rats in the Shuigou groups underwent acupuncture and continuous wave
      stimulation at a frequency of 2 Hz, 50 Hz or 100 Hz (intensity 1 mA) for 10 min
      twice daily for 3 days. The control and model groups underwent no intervention.
      Zausinger 6-point neurological function score and MEPs were measured 72 h after
      the start of treatment. RESULTS: The neurological function scores of the three
      Shuigou groups were significantly higher than those of the model group (P <
      0.05). There was no significant difference between sides in the latency and
      amplitude of MEPs in the model group (P > 0.05). The latency on the affected side
      in the model group was significantly longer than that in the control group (P <
      0.05) and the amplitude on affected side was significantly reduced (P < 0.01).
      After 3 days of electro-acupuncture, the latency on the affected side in the 2 Hz
      Shuigou group was significantly shortened (P < 0.05) and the amplitude was
      significantly increased (P < 0.05) compared with the model group. CONCLUSION: Low
      frequency electro-acupuncture at Shuigou (GV 26) can promote recovery of motor
      function after focal cerebral ischemic injury in rats.

PMID- 22594112
TI  - Influence of acupuncture on neural movement function in rats with middle cerebral
      artery occlusion--a randomized controlled trial.
AB  - OBJECTIVES: To observe recovery in movement function in rats with middle cerebral
      artery occlusion (MCAO) after acupuncture treatment. METHODS: According to the
      randomized and controlled principle 1384 rats were divided into the basic control
      group (including the normal, sham, model control, model without intervention,
      Nimodipine, and para-Renzhong groups) and the acupuncture group (including the
      Neiguan (PC 6), Weizhong (BL 40), Sanyinjiao (SP 6), Chize (LU 5), Renzhong (GV
      6) and non-acupoint groups). MCAO was modeled by Zea-longa's thread ligation and
      rats with scores of 1-3, as assessed by Zausinger's six-point method, were used
      in this study. Moreover, in the acupuncture group each acupoint was set with 12
      different parameters by the orthogonal intersection method, resulting in 78
      groups with 18 rats per group. The rats were treated by acupuncture once every 12
      h for a total of six sessions and neurobehavioral scores were measured after each
      session. The neurobehavioral scores were compared by one-way ANOVA using the
      statistical software SPSS 17.0. RESULTS: After acupuncture therapy the mean
      neurobehavioral scores in MCAO rats increased gradually at each time point with a
      significant difference among the six scores, but with no significant differences
      between the fourth (48 h) and the fifth score (60 h), and between the fifth (60
      h) and the sixth (72 h) score (P > 0.05). CONCLUSIONS: MCAO rats gradually
      recovered movement function over multiple acupuncture sessions. After the fouth
      acupuncture session (48 h), the neurobehavioral scores of rats with cerebral
      infarction remained stable. Acupuncture treatment had a reliable curative effect
      on movement function in cerebral infarction rats.

PMID- 22594113
TI  - Research ideas and strategies on the dose-effect relationship of traditional
      Chinese medicine prescriptions and herbs.
AB  - We discuss here the complexity of the doses of traditional Chinese medicine (TCM)
      prescriptions and herbs from different viewpoints, including the heterogeneity of
      drug quality, the flexibility of prescriptions, and the diversity of drug
      effects. Then, the corresponding research ideas and strategies are proposed. We
      can reveal the actual situation of clinical doses based on in-depth "real-world
      study" of the safety and effectiveness of TCM prescriptions, create an analytical
      method for dose-effect relationships in accordance with the features of TCM, and
      reveal the correlated regular nature of the effectiveness and dosage of TCM
      prescriptions and herbs.

PMID- 22594114
TI  - Biological macro-idea and criterion of osteopathic fracture immobilization in
      China's traditional Mongolian medicine.
AB  - OBJECTIVE: To investigate the biological macro-idea and criterion of osteopathic
      fracture immobilization in China's traditional Mongolian medicine. METHODS: Based
      on biological naturalism regarding the relationship between man and universe
      (including psychosomatic integration) in osteopathic fracture immobilization in
      China's traditional Mongolian medicine, we used modern physiopsychological and
      biomechanical principles and methods to investigate the biological macro
      characteristics of humanization, behaviorism, and wholism in "dynamic" fixation
      of fractures. RESULTS: Osteopathic fracture immobilization in China's traditional
      Mongolian medicine is based on the fixation criterion of macro-idea and method as
      well as on geometry, mechanics, motion, and stress and psychological stability in
      "non-sheltered fixation" of fractures contained in the life view of nature,
      regarding the relationship between man and universe (including psychosomatic
      integration) and on harmony between the limbs and the whole body, between body
      and function, and between man and nature. CONCLUSIONS: Osteopathic fracture
      immobilization in China's traditional Mongolian medicine is fixation without
      trauma or shelter. The principle and method of whole, dynamic, and functional
      fixation of fractures is not only radical, but also represents a new direction
      for developing the principle and method of fracture immobilization.

PMID- 22594115
TI  - Correlative analysis of neoplasm patients with phlegm-stasis or abnormal Savda
      syndrome, based on metabonomics.
AB  - OBJECTIVE: To investigate plasma samples from neoplasm patients with phlegm
      stasis or abnormal Savda syndrome, with NMR spectroscopy, and to analyze their
      metabolic varieties, characteristics and reciprocity. METHODS: 1H-NMR spectra
      were analyzed using the orthogonal projection to latent structure with
      discriminative analysis (OPLS-DA) method with unit variance scaling. The
      discriminative significance of metabolites was determined by the Pearson's
      product - moment correlation coefficient. RESULTS: Compared to the control group,
      neoplasm patients with phlegm - stasis or abnormal Savda syndrome had low
      concentrations of leucine, isoleucine, valine, alanine, tyrosine, histidine,
      citrulline, glycoprotein, glutamine, myo-inositol, scyllo-inositol, creatine,
      alpha-glucose, alpha-glucose and lactate (P < 0.05), and high concentrations of
      very low density lipoprotein, low density lipoprotein, unsaturated lipid,
      formate, acetone, acetate, acetoacetate, pyruvate, beta-hydroxybutyrate,
      carnitine and malonic acid (P < 0.05), with no significant differences between
      the phlegm - stasis and abnormal Savda syndrome patients. CONCLUSIONS: Neoplasm
      patients with different syndromes have very similar metabolic changes. A series
      of abnormalities such as immune dysfunction and oxidative - antioxidative
      imbalance, occur in neoplasm patients with abnormal Savda or phlegm - stasis
      syndrome.

PMID- 22594116
TI  - Economic evaluation of treating herpes zoster with various methods of acupuncture
      and moxibustion.
AB  - OBJECTIVE: To analyze the cost effect of surrounding acupuncture plus electric
      acupuncture, cotton-sheet moxibustion, puncturing with red-hot needles, tapping
      plus cupping on herpes zoster. METHODS: Five hundred patients with herpes zoster
      were randomly divided into group A (surrounding acupuncture plus electric
      acupuncture), group B (cotton-sheet moxibustion), group C (puncturing with red
      hot needles), group D (tapping plus cupping), and group E (Western medicine). The
      treatment was carried out twice a day in group E and once a day in the other four
      groups. The curative effect was observed on the 10th day of treatment; the cost
      was calculated for the five therapies, and the cost-effect ratio (C/E) and
      increment ratio (delta C/delta E) were analyzed. RESULTS: After the 10-day
      treatment, there was no statistical difference (P > 0.05) in the curative effect
      among the five groups. Pain being alleviated one day faster than in group E
      amounted to a saving of RMB 21.90 yuan in group A, a saving of RMB 21.87 yuan in
      group B, a saving of RMB 26.00 yuan in group C, and a saving of RMB 20.23 yuan in
      group D. Compared with group C, the values of delta C/delta E were RMB 1.55,
      2.81, and 0.21 yuan in groups A, B, and D, respectively. CONCLUSIONS: The
      curative effect in groups A, B, C, and D was similar to that in group E, but the
      C/E was better than in group E.

PMID- 22594117
TI  - Gender deviance and household work: the role of occupation.
AB  - This article takes a new approach to gender and housework by identifying a new
      measure of gender deviance--work in gender-atypical occupations--and by arguing
      that men who do "women's work" and women who do "men's work" in the labor market
      may seek to neutralize their gender deviance by doing male- and female-typed work
      at home. Analysis of data from the National Survey of Families and Households and
      the 2003-7 waves of the American Time Use Survey shows that men who do "women's
      work" in the market spend more time on male-typed housework relative to men in
      gender-balanced occupations and their wives spend more time on female-typed
      housework. Women in gender-atypical occupations also do more female-typed
      housework than women in gender-balanced occupations. The article provides clearer
      evidence about the important ways in which cultural conceptions of gender shape
      and are shaped by economic processes.

PMID- 22594118
TI  - Settler colonial power and the American Indian sovereignty movement: forms of
      domination, strategies of transformation.
AB  - The article extends the multi-institutional model of power and change through an
      analysis of the American Indian Sovereignty Movement. Drawing upon cultural
      models of the state, and articulating institutionalist conceptions of political
      opportunities and resources, the analysis demonstrates that this framework can be
      applied to challenges addressing the state as well as nonstate fields. The
      rational-legal diminishment of tribal rights, bureaucratic paternalism,
      commonsense views of tribes as racial/ethnic minorities, and the binary
      construction of American and Indian as oppositional identities diminished the
      appeal of "contentious" political action. Instead, to establish tribes' status as
      sovereign nations, tribal leaders aggressively enacted infrastructural power,
      transposed favorable legal rulings across social fields to legitimize sovereignty
      discourses, and promoted a pragmatic coexistence with state and local
      governments. Identifying the United States as a settler colonial society, the
      study suggests that a decolonizing framework is more apt than racial/ethnicity
      approaches in conceptualizing the struggle of American Indians.

PMID- 22594119
TI  - Human rights as myth and ceremony? Reevaluating the effectiveness of human rights
      treaties, 1981-2007.
AB  - Much research has shown human rights treaties to be ineffective or even
      counterproductive, often contributing to greater levels of abuse among countries
      that ratify them. This article reevaluates the effect of four core human rights
      treaties on a variety of human rights outcomes. Unlike previous studies, it
      disaggregates treaty membership to examine the effect of relatively "stronger"
      and "weaker" commitments. Two-stage regression analyses that control for the
      endogeneity of treaty membership show that stronger commitments in the form of
      optional provisions that allow states and individuals to complain about human
      rights abuses are often associated with improved practices. The article discusses
      the scholarly and practical implications of these findings.

PMID- 22594120
TI  - Citizenship rights for immigrants: national political processes and cross
      national convergence in western Europe, 1980-2008.
AB  - Immigrant citizenship rights in the nation-state reference both theories of cross
      national convergence and the resilience of national political processes. This
      article investigates European countries' attribution of rights to immigrants:
      Have these rights become more inclusive and more similar across countries? Are
      they affected by EU membership, the role of the judiciary, the party in power,
      the size of the immigrant electorate, or pressure exerted by anti-immigrant
      parties? Original data on 10 European countries, 1980-2008, reveal no evidence
      for cross-national convergence. Rights tended to become more inclusive until
      2002, but stagnated afterward. Electoral changes drive these trends: growth of
      the immigrant electorate led to expansion, but countermobilization by right-wing
      parties slowed or reversed liberalizations. These electoral mechanisms are in
      turn shaped by long-standing policy traditions, leading to strong path dependence
      and the reproduction of preexisting cross-national differences.

PMID- 22594121
TI  - Re: Cricothyroidotomy bottom-up training review: battlefield lessons learned. Mil
      Med 2011, 176: 1311-1319.

PMID- 22594122
TI  - Re: Isolated hand injuries on operational deployment: an examination of
      epidemiology and treatment strategy. Mil Med 2011; 176: 1404-1407.

PMID- 22594123
TI  - Tropical medicine training in the Department of Defense.

PMID- 22594124
TI  - Gardening in a desert.

PMID- 22594125
TI  - Postdeployment mental health screening: an application of the Soldier Adaptation
      Model.
AB  - The Global War on Terrorism and its corresponding frequent and long deployments
      have resulted in an increase in mental health concerns among active duty troops.
      To mitigate these impacts, the Department of Defense has implemented
      postdeployment screening initiatives designed to identify symptomatic soldiers
      and refer them for mental health care. Although the primary purpose of these
      screenings is to identify and provide assistance to individuals, macrolevel
      reporting of screening results for groups can assist Commanders, who are charged
      with ensuring the wellbeing of their soldiers, to make unit-level interventions.
      This study assesses the utility of a metatheory of occupational stress, the
      Soldier Adaptation Model, in organizing feedback information provided to Army
      Commanders on their units' postdeployment screening results. The results of a
      combat brigade of 2319 soldiers who completed post-deployment screening following
      return from Iraq were analyzed using Structural Equation Modeling to assess the
      Soldier Adaptation Model's use for macrolevel reporting. Results indicate the
      Soldier Adaptation Model did not strengthen the macrolevel reporting; however,
      alcohol use and reckless driving were found to mediate the relationship between
      combat exposure and numerous mental health symptoms and disorders (e.g., post
      traumatic stress disorder, anger, depression, anxiety, etc.). Research and
      practice implications are discussed.

PMID- 22594126
TI  - A noncognitive temperament test to predict risk of mental disorders and attrition
      in U.S. Army recruits.
AB  - U.S. military accession mental health screening includes cognitive testing and
      questions regarding the applicants' past mental health history. This process
      relies on applicants' knowledge of and willingness to disclose symptoms and
      conditions. Applicants have a strong incentive to appear qualified, which has
      resulted in a long history of frequent mental health conditions presenting during
      recruit training. OBJECTIVE: To assess the predictive value of a pre-enlistment
      noncognitive temperament test score for risk of mental disorders and attrition in
      the first year of service. METHODS: A retrospective cohort study was conducted on
      non-high school diploma U.S. Army active duty recruits who took the Assessment of
      Individual Motivation (AIM). Multivariate logistic regression models were used to
      determine associations between AIM score quintiles, mental disorders, and
      attrition. RESULTS: AIM scorers in the lowest quintile were at increased risk for
      a mental disorder (OR, 1.44; 95% CI, 1.35-1.53) and of discharge (OR, 1.65; 95%
      CI, 1.44-1.68) compared to AIM scorers in the highest quintile, with significant
      linear trends for decreased risk with increasing AIM score. CONCLUSIONS: AIM
      offers the potential to improve screening of military applicants and reduce
      mental disorders and attrition in new recruits beyond the current process.

PMID- 22594127
TI  - Psychiatric diagnoses and treatment of U.S. military personnel while deployed to
      Iraq.
AB  - Military personnel deployed in support of combat operations are at significantly
      higher risk for mental health problems. However, much of what we know about
      combat-related mental health comes from postdeployment assessments. This study
      describes the mental health of 1,336 treatment-seeking deployed U.S. military
      personnel and interventions recommended by military mental health providers in
      Iraq from January 2006 to January 2007. Cases were primarily young enlisted men,
      most of whom were on their first combat deployment. Marines made up the majority
      of the cases (60%), but there were also large numbers of Army and Navy personnel.
      The most common psychiatric diagnoses were anxiety disorders (31%, including 11%
      with posttraumatic stress disorder), followed by adjustment (27%) and mood
      disorders (25%, including 22% with depression). Medication was the most commonly
      prescribed treatment for patients with psychiatric diagnoses but was often
      combined with recommendations for psychotherapy/counseling and/or behavioral
      modifications. The findings illustrate the distribution of mental health
      conditions seen among treatment-seeking troops while actively serving in a combat
      environment and the interventions recommended for them. Further examination of
      postdeployment health outcomes may help to facilitate the development of more
      effective acute intervention strategies in theater.

PMID- 22594128
TI  - An exploratory examination of risk-taking behavior and PTSD symptom severity in a
      veteran sample.
AB  - The present study conducted an exploratory examination of the relationship
      between self-reported symptoms of post-traumatic stress disorder and an expanded
      definition of risk-taking behaviors among 395 veterans at a large Midwestern
      Veterans Affairs Medical Center. Post-traumatic stress disorder symptoms were
      associated with elevated rates of substance use, thrill seeking, aggression,
      risky sexual practices, and firearm possession. Results indicated that suicidal
      ideation and aggressive driving behavior were among the most frequently reported.
      The present findings hold significant public health implications and highlight
      the need to attend to risk-taking behaviors in treatment planning.

PMID- 22594129
TI  - Evaluation of a third-location decompression program for Canadian Forces members
      returning from Afghanistan.
AB  - BACKGROUND: Service members returning from combat can experience difficulty
      adapting to home life. To help ease this transition, the Canadian Forces provides
      a Third-location Decompression (TLD) program in Cyprus to members returning from
      deployment to Afghanistan. METHODS: The 5-day program consists of individual free
      time, structured recreational activities, and educational programming. Its
      perceived value and impact were measured immediately afterward and 4 to 6 months
      later. RESULTS: Respondents overwhelmingly supported the TLD concept, with 95%
      agreeing that "some form of TLD is a good idea." Eighty-one percent of
      participants found the program valuable, and 83% recommended it for future
      deployments to Afghanistan. Perceived value persisted 4 to 6 months after return,
      and 74% felt that it helped to make reintegration easier for them. CONCLUSION:
      Canadian Forces members saw value in the TLD program, and most members believed
      that the program had its intended effect of making the reintegration process
      easier for them.

PMID- 22594130
TI  - An epidemiologic investigation of homicides at Fort Carson, Colorado: summary of
      findings.
AB  - In response to an apparent clustering of homicides at Fort Carson, Colorado, the
      U.S. Army Public Health Command (formerly the U.S. Army Center for Health
      Promotion and Preventive Medicine) Behavioral and Social Health Outcomes Program
      conducted a multidisciplinary epidemiologic consultation to identify factors
      contributing to violent behavior among soldiers at Fort Carson. This article
      summarizes the findings of the epidemiologic consultation report as provided to
      the Secretary of the Army and the Fort Carson Senior Mission Commander and
      released in its entirety publicly July 2009 and elaborates on the mixed-methods
      analytic approach used to study a complex behavioral issue at the community
      level. To aid in answering the key study questions, six study arms were designed
      and carried out: (1) index case analysis, (2) confinee interviews, (3) analysis
      of installation-level trends, (4) retrospective cohort analysis, (5) soldier
      focus groups and interviews, and (6) aggression risk factors survey. Although not
      conclusive, the findings suggest a combination of individual, unit, and
      environmental factors converged to increase the risk of violent behaviors, which
      made clustering of negative outcomes more likely.

PMID- 22594131
TI  - Role of the battalion surgeon in the Iraq and Afghanistan War.
AB  - The battalion surgeon is an invaluable asset to a deploying unit. The primary
      role of a battalion surgeon is to provide basic primary care medicine and combat
      resuscitation. Other expectations include health care screening, vaccinations,
      supervision of medics, and being a medical advisor to the unit's commander. As
      many physicians who fill this role previously worked at medical treatment
      facilities or medical centers without prior deployment experience, the objective
      of this article is to highlight some of the challenges a battalion surgeon may
      encounter before, during, and following deployment.

PMID- 22594132
TI  - Temporary disability retirement cases: variations in time to final disposition
      and disability rating by service and medical condition.
AB  - OBJECTIVE: Service members undergoing disability evaluation are placed on the
      temporary disability retirement list (TDRL) when their disabling medical
      condition(s) may change in severity over time. Information is sparse on the
      epidemiology of the TDRL population and factors influencing time spent on the
      TDRL or changes in compensation ratings before final disability outcome. METHODS:
      A cross-sectional study was conducted on U.S. Army, Navy, and Marine Corps
      personnel placed on the TDRL between fiscal years 2005 to 2009. RESULTS:
      Approximately 85% of cases were finalized at first re-evaluation and more than
      75% were permanently retired. Overall, about 50% of cases retained the same
      disability rating throughout the process. Cases with medical conditions within
      two or more body systems were more likely to be permanently retired and receive a
      change in disability rating than those with medical condition(s) within a single
      body system. CONCLUSIONS: Most cases retained the same disability rating and were
      permanently retired by the first re-evaluation. Important areas of future
      research include cost-benefit analyses to determine if length of time currently
      allowable on the TDRL can be shortened or if repeated evaluations are necessary
      and exploration of specific medical conditions likely to change in severity over
      time.

PMID- 22594133
TI  - Military medical advances resulting from the conflict in Korea, Part I: Systems
      advances that enhanced patient survival.
AB  - The Korean War started several years after the World War II had ended and no
      recognition of the threat or preparation was made for this possibility. The
      military and its medical service had been downsized after World War II and had to
      quickly ramp up to meet the surprise attack. The war provided the laboratory for
      trials and experimentation with the new technological developments of the era.
      The Korean conflict led to numerous advances in medical systems and patient care.
      The Mobile Army Surgical Hospital came of age, and was instrumental in saving
      many lives. Helicopters saw their first regular use as flying ambulances to take
      the injured to definitive care in a timely fashion. The national blood banking
      program was rapidly geared up and new techniques such as plastic bags for
      collection and delivery resulted. Body armor was developed that would allow
      mobility while offering protection and was widely used for the first time. Each
      of these systems improvements saved the lives of soldiers in combat and were soon
      to be used in the civilian sector to save and improve lives around the world.

PMID- 22594134
TI  - Military medical advances resulting from the conflict in Korea, Part II: Historic
      clinical accomplishments.
AB  - Throughout the recorded history of civilization, there has been armed conflict.
      Warfare has been associated with advances in care for the wounded. Many of these
      advances when shown effective on the battlefield become incorporated into
      civilian health care. It is a laboratory where there is unfortunately much
      clinical material and presents opportunity for the creative, curious, and
      innovative. This article reviews the medical advances that resulted from the
      Korean War. There were notable advances in neurosurgery, vascular surgery, and
      plastic surgery. Tools from prior wars were rediscovered, dusted off, and used to
      stop combat losses from psychiatric trauma. A treatment was developed for cleft
      lip by a plastic surgeon, thus giving hope to young lives. War is a disruptive,
      destructive, and harrowing experience--but can lead to improvements in care for
      the wounded and these developments can improve the lives of people everywhere.

PMID- 22594135
TI  - Divided listening in noise in a mock-up of a military command post.
AB  - This study investigated divided listening in noise in a mock-up of a vehicular
      command post. The effects of background noise from the vehicle, unattended speech
      of coworkers on speech understanding, and a visual cue that directed attention to
      the message source were examined. Sixteen normal-hearing males participated in
      sixteen listening conditions, defined by combinations of the absence/presence of
      vehicle and speech babble noises, availability of a vision cue, and number of
      channels (2 or 3, diotic or dichotic, and loudspeakers) over which concurrent
      series of call sign, color, and number phrases were presented. All wore a
      communications headset with integrated hearing protection. A computer keyboard
      was used to encode phrases beginning with an assigned call sign. Subjects
      achieved close to 100% correct phrase identification when presented over the
      headset (with or without vehicle noise) or over the loudspeakers, without vehicle
      noise. In contrast, the percentage correct phrase identification was
      significantly less by 30 to 35% when presented over loudspeakers with vehicle
      noise. Vehicle noise combined with babble noise decreased the accuracy by an
      additional 12% for dichotic listening. Vision cues increased phrase
      identification accuracy by 7% for diotic listening. Outcomes could be explained
      by the at-ear energy spectra of the speech and noise.

PMID- 22594136
TI  - Predicting neck pain in Royal Australian Air Force fighter pilots.
AB  - OBJECTIVE: Fighter pilots frequently report neck pain and injury, and although
      risk factors have been suggested, the relationships between risk factors and neck
      pain have not been quantified. The aim of this study was to identify personal and
      work behaviors that are significantly associated with neck pain in fighter
      pilots. METHODS: Eighty-two Royal Australian Air Force fighter pilots were
      surveyed about their flying experience, neck pain prevalence, and prevention.
      Multinomial logistic regressions were used to fit models between pilots' neck
      pain during and after flight and a range of personal and work characteristics.
      RESULTS: In-flight neck pain was very weakly, yet positively associated with
      flight hours. Duration of postflight pain was positively associated with the
      weekly desktop work hours and the sum of preventative actions taken in flight.
      The duration pilots were considered temporarily medically unfit for flying was
      positively associated with pilots' age and their weekly desktop work hours.
      DISCUSSION: The risk factors identified by the current study should guide neck
      pain prevention for fighter pilots. In particular, reducing desktop working hours
      as well as incorporating specific neck-strengthening exercises and in-flight
      bracing actions should be considered by agencies to help alleviating neck pain in
      their pilots.

PMID- 22594137
TI  - Assessment of cognitive function while on low-dose propranolol: implications for
      usage by survivors in a disabled submarine.
AB  - While awaiting rescue from a disabled submarine (DISSUB), survivors will likely
      endure an atmosphere of rising CO2 which will eventually be lethal. Previously,
      it was determined that low-dose propranolol reduces resting metabolic carbon
      dioxide production and therefore may increase survival time in this scenario. The
      actions and decisions survivors would carry out in a DISSUB situation would
      require an unaltered cognition state. Therefore, we wanted to determine if low
      dose propranolol impairs cognitive function. Eight healthy males completed a
      counterbalanced, randomized, placebo-controlled, double-blinded crossover study
      in which each subject received propranolol (40 mg twice daily) or placebo
      (lactose pill twice daily) over a 72-hour period. The alternate condition was
      separated by a minimum 96-hour washout period. Subjects performed a series of 6
      tasks from the Automated Neuropsychological Assessment Metrics (ANAM) battery and
      answered a self-report sleepiness scale each morning and afternoon. Subjects
      exhibited increased accuracy in one of the ANAM tasks while on propranolol
      compared to placebo, but showed no difference between treatments on the other 5
      tasks and sleepiness scale. These results suggest that 40 mg of propranolol taken
      twice daily does not significantly impair cognitive function and may be a viable
      option for use in a DISSUB scenario.

PMID- 22594138
TI  - A 5-year retrospective review of experience with Clostridium difficile-associated
      diarrhea.
AB  - The incidence and virulence of Clostridium difficile-associated diarrhea (CDAD)
      has increased dramatically from the mid 1990s to the mid 2000s. This research
      assessed recent CDAD patterns at a major military medical center from 2005 to
      2009, by retrospectively reviewing clinical data of each CDAD case identified
      using the center's electronic medical record system. Two hundred and thirty-two
      cases were identified. There was a stable incidence rate for both inpatient (2.6
      4.3/1000) and outpatient (0.02-0.04/1000) infections. Overall mortality rate was
      9%. Among inpatient cases, 49% were considered to be severe, with an associated
      mortality of 19%. Only 12% (9/77) of severe cases were treated initially with
      oral vancomycin, with the majority (8/9) treated in 2009. Hospitalization was a
      risk factor in 71% of cases, with 29% community-acquired. Other risk factors
      included recent antibiotic usage (83%) and proton-pump inhibitor use (60%), with
      8% having no risk factors. Most cases were initially treated with metronidazole,
      which was associated with a 14% (27/188) recurrence rate versus 9% (2/22) treated
      with vancomycin (p > 0.05). In contrast to earlier reports, our center has
      experienced a low and stable rate of CDAD since 2005. Severe CDAD is common and
      associated with significant mortality.

PMID- 22594139
TI  - Leishmania detection in sand flies using a field-deployable real-time analytic
      system.
AB  - We describe here the development and evaluation of advanced vector surveillance
      analytic technologies for real-time leishmaniasis risk assessment. Leishmania
      genus and visceral leishmaniasis causative agent--specific dual fluorogenic-probe
      hydrolysis (TaqMan), thermally stable (freeze-dried) polymerase chain reaction
      assays were developed using field-durable analytic instrumentation. In laboratory
      testing with a panel of diverse Leishmania species from culture and infected sand
      flies, the sensitivity and specificity of both assays were 100% concordant with
      DNA sequencing. In specificity testing with Leishmania genetic near neighbors,
      clinically significant organisms, and human genomic DNA, no detectable
      fluorescence above background was observed. Field evaluation was conducted in
      southern Iraq using wild sand flies. In field testing, Leishmania genus assay was
      100% sensitive and 96% specific with a single false-positive result. The visceral
      leishmaniasis genotype assay was 100% sensitive and 100% specific compared to DNA
      sequencing. Thermally stable polymerase chain reaction assays vastly simplified
      transportation and storage. Assay preparation and analysis required less than 2
      hours.

PMID- 22594140
TI  - Yellow fever vaccine-associated viscerotropic disease.
AB  - Yellow fever is a mosquito-transmitted hemorrhagic viral disease that is endemic
      to tropical regions in South America and Africa. It remains a significant health
      concern for deploying military personnel, accordingly vaccination is frequently
      performed on troops. Although the vaccine is generally administered with only
      minor complications, rare severe complications are also reported. Herein, we
      report a mild case of yellow fever vaccine-associated viscerotropic disease 4
      days after administration of the vaccine. The various complications of the
      vaccine and their pathogenesis are also reviewed.

PMID- 22594141
TI  - Peripartum cardiomyopathy and acute fatty liver of pregnancy: one patient with
      two zebras.
AB  - OBJECTIVE: Peripartum cardiomyopathy (PPCM) and acute fatty liver of pregnancy
      (AFLP) are rare complications of pregnancy affecting approximately 1/10,000
      pregnancies each. We describe a patient who had biopsy-proven AFLP complicated by
      PPCM. METHODS: Chart review and literature search. RESULTS: The patient is a 22
      year-old G5P1213 obese African-American female who presented at 30 weeks
      gestation with abdominal pain. She had normal blood pressures and mildly elevated
      liver enzymes. After completion of a 24 hour urine protein collection that was
      consistent with pre-eclampsia, an induction of labor with uncomplicated vaginal
      delivery was accomplished. Following delivery, a computed tomography scan of the
      abdomen revealed significant cardiomegaly. An echocardiogram revealed global
      dysfunction with an ejection fraction of 10%. Liver biopsy showed AFLP. Attempts
      to establish a unifying etiology were unrevealing. The PPCM was treated with
      diuretics and intravenous immunoglobulin. The patient's clinical status
      deteriorated, eventually requiring continuous dialysis, intubation, pharmacologic
      and mechanical inotropic support, and a feeding tube. The patient was discharged
      to a long-term care facility where she subsequently passed away from multiorgan
      failure. CONCLUSION: AFLP and PPCM are rare complications of pregnancy. We
      present a patient who had both. Both diseases carry a high mortality rate, and
      together, are likely fatal.

PMID- 22594142
TI  - Iatrogenic pneumomediastinum and subcutaneous emphysema as a complication of
      colonoscopy with cold forceps biopsy.
AB  - A 58-year-old woman underwent outpatient colonoscopy with multiple cold forceps
      biopsy for evaluation of a presumptive diagnosis of ulcerative colitis. Six hours
      following the procedure, she developed subcutaneous crepitus and presented to the
      emergency department, where chest X-ray revealed pneumomediastinum and
      subcutaneous emphysema. Our case discusses this unusual complication of
      colonoscopy and its diagnosis and management.

PMID- 22594143
TI  - A case report of lymphangioleiomyomatosis presenting as spontaneous pneumothorax.
AB  - Spontaneous pneumothorax is a commonly encountered problem in the Emergency
      Department. Patients are often treated without further investigation for an
      underlying etiology. We present a patient who was unable to completely resolve a
      pneumothorax and was found to have lymphangioleiomyomatosis (LAM), a rare cystic
      lung disease. In the past, LAM was difficult to diagnose and had a mortality of
      100% after 10 years, but now there is a 71% survival after 10 years. Recent
      research has led to increased characterization of the pathology and radiographic
      findings. This article briefly presents the case and discusses the etiology,
      diagnosis, and treatment of LAM.

PMID- 22594145
TI  - The physician trustee. Balancing clinical perspective and conflicts of interest.
AB  - In addition to his or her clinical perspective, a physician on the board brings
      the risk of conflicts of interest.

PMID- 22594144
TI  - Compensation in question. Executives who substitute cash for benefits create
      unintended regulatory and quality consequences.
AB  - When executives convert benefit dollars to cash, their compensation invites
      regulatory scrutiny.

PMID- 22594146
TI  - The ACO wake-up call. A hospital confronts payment reform with a physician joint
      venture.
AB  - A hospital responds to payment reform with a uniquely structured physician joint
      venture.

PMID- 22594147
TI  - Mission-based decision-making for boards.

PMID- 22594148
TI  - It takes a community. To save their hospital and local economy, trustees turned
      to residents for support.
AB  - To save their hospital and energize their community, trustees convinced residents
      to renew their tax support.

PMID- 22594149
TI  - Technologies to watch. The latest medical treatments and techniques call for
      quick thinking.
AB  - Staying up-to-date on the latest devices and techniques means staying
      competitive.

PMID- 22594150
TI  - Board survival strategies. As the trustee role becomes more complex, here are 10
      ways to weather the storms.
AB  - Adopting survival strategies can help trustees manage the complexities of board
      service.

PMID- 22594151
TI  - Embracing change, quickly. A hospital finds success by rapidly implementing new
      processes to curb costs and boost quality.
AB  - The speed with which process improvements are implemented can be critical to
      their success.

PMID- 22594152
TI  - The future of medicine.

PMID- 22594153
TI  - Things to look out for in EHR contracts.

PMID- 22594154
TI  - Care managers are an emerging new component of Michigan health care.

PMID- 22594155
TI  - Electronic medical record and social media malpractice risks.

PMID- 22594156
TI  - Exchanging health care information in Michigan: a snapshot.

PMID- 22594157
TI  - EHR meaningful use incentives begin to flow.

PMID- 22594158
TI  - Professionalism today: challenge and opportunity.

PMID- 22594159
TI  - The role of information technology in alliance action.

PMID- 22594160
TI  - Team-based care education delivers positive results.

PMID- 22594161
TI  - HPV vaccine is safe and effective and is now routinely recommended for preteen
      girls and boys.

PMID- 22594163
TI  - FFS v ACO: a new beginning.

PMID- 22594162
TI  - Use of hepatitis B vaccination for adults with diabetes mellitus.

PMID- 22594164
TI  - Joint Commission identifies top standards compliance issues for 2011.

PMID- 22594165
TI  - The Joint Commission enterprise launches HAI Portal.

PMID- 22594166
TI  - Accreditation manual updates to mail to all accredited organizations.

PMID- 22594167
TI  - [Baby abandonment and anonymous delivery under criticism].

PMID- 22594168
TI  - [Allergic diseases in childhood: new data regarding the hygiene hypothesis].

PMID- 22594169
TI  - [Self efficacy and mindfulness. Innovative concepts in health promotion of
      socially disadvantaged persons].

PMID- 22594170
TI  - [Nursing care for a child with recurrent neuroblastoma treated with
      immunotherapy].

PMID- 22594171
TI  - [Measles. 2010 elimination goal missed?].

PMID- 22594172
TI  - [Discharge management with a primary nurse].

PMID- 22594174
TI  - [More and more children take psychotropic drugs - the number sometimes more than
      doubled].

PMID- 22594175
TI  - [Early skin contact in cesarean section birth. Practical experiences and aspects
      of continuous mother-child skin contact during cesarean section and the first
      hours of life].

PMID- 22594176
TI  - [Intelligent and slim: the first nursing documentation system especially for home
      pediatric nursing care].

PMID- 22594178
TI  - [Principles of family oriented nursing].

PMID- 22594179
TI  - At last, a common sense approach to prescribing.

PMID- 22594180
TI  - Nurse independent prescribers win parity over controlled drugs.

PMID- 22594181
TI  - Change to immigration rules poses 'significant' threat to patient safety.

PMID- 22594182
TI  - Nurse specialists back government drive to transform dementia care.

PMID- 22594183
TI  - Higher-performing trusts employ more nurses than low performers.

PMID- 22594184
TI  - Getting ratios right, for the patients' sake.
AB  - Good staffing is one of the ten priorities for action identified by Nursing
      Standard's Care campaign. Diluting skill mix is tempting for NHS executives when
      finances are tight, but evidence is mounting that this puts patient care at risk.

PMID- 22594185
TI  - A tool for commissioners.

PMID- 22594186
TI  - Time to see the light.
AB  - There is growing concern about low vitamin D levels in the UK population, and
      children from a range of backgrounds are now presenting with rickets, the bone
      disease associated with poor nutrition in the 19th century. However, the evidence
      linking vitamin D deficiency to a range of conditions unconnected to bone health,
      such as heart disease and multiple sclerosis, is inconclusive.

PMID- 22594187
TI  - Finding their way.
AB  - Hospitals can be disorientating for blind and partially sighted inpatients.
      Simple measures, such as explaining the ward layout on admission, can make a big
      difference. Ophthalmic nurses can also provide support.

PMID- 22594188
TI  - A thrombolysis pathway for patients following acute ischaemic stroke.
AB  - Thrombolysis is a promising treatment for patients with acute ischaemic stroke.
      However, a major barrier to treatment is that it needs to be administered within
      4.5 hours of stroke onset. Training and education is key to the timely delivery
      of thrombolytic therapy to patients following acute stroke. This article
      describes the thrombolysis care pathway in use in one hyperacute stroke unit and
      outlines the core competencies required of the acute stroke nurse.

PMID- 22594189
TI  - Translating an academic module into an online resource.
AB  - Blended learning, which combines face-to-face sessions with online work, is used
      to provide flexible learning and courses for students who are geographically
      dispersed. Canterbury Christ Church University recognised the importance of
      developing an academic module for dispensing opticians across the UK and the
      requirement to address the needs of an increasingly diverse population of
      students. Following interest in the module from the Association of British
      Dispensing Opticians, a decision was made to reformat the module into an online
      resource. This article describes some of the pedagogical processes involved in
      developing the online resource. Quantitative and qualitative data are analysed to
      identify challenges and successes. The importance of developing an educational
      biography to achieve depth of understanding and thought is acknowledged. The
      article concludes that some face-to-face interaction is still necessary, not
      least for helping to reduce students' anxiety.

PMID- 22594190
TI  - Promoting and maintaining healthy hydration in patients.
AB  - Fluid is essential for life and health. Nurses have an important role in helping
      patients maintain optimal levels of hydration, particularly in hospital or
      residential settings where access to fluid is less likely to be under the
      patient's control. This article describes the benefits of healthy hydration,
      outlines guidelines on fluid requirements for different patient groups and
      discusses which beverages should be promoted. Myths about caffeine consumption
      and hydration will also be addressed using new clinical evidence.

PMID- 22594191
TI  - Mentorship.

PMID- 22594193
TI  - Build an instinct for feelings.

PMID- 22594192
TI  - A position of strength.

PMID- 22594194
TI  - Learning for life support.

PMID- 22594195
TI  - Building resilience in the nursing workforce.

PMID- 22594196
TI  - Lansley prepares to justify reforms to thousands of critics at congress.

PMID- 22594197
TI  - Bitter disappointment at decision to drop student 'misconduct' index.

PMID- 22594198
TI  - One year on, the real cost of the pay freeze.

PMID- 22594199
TI  - Building resilience.
AB  - The nature of nurses' work can take a heavy physical and emotional toll which, if
      left unchecked, can have a detrimental effect on patient care. Employers can
      promote staff wellbeing by providing appropriate support, leadership and
      supervision.

PMID- 22594200
TI  - Blackpool sees the start of a revolution.
AB  - An acute trust in Blackpool has embarked on a major project to examine every
      aspect of the patient experience, from the quality of nursng care to how easily
      patients can find their way around the hospital. Clinical staff and managers hope
      to make a big difference by getting 'many little things' right. This means
      understanding the emotional 'crunch points' that matter to patients.

PMID- 22594201
TI  - A tale of two nurses.
AB  - Two nurses were among the 2,200 crew and passengers on board the Titanic when it
      sank on its maiden voyage to New York on April 141912. Hospital matron Catherine
      Wallis, who worked with passengers in third class, was among the 1,500 people who
      died. Caroline Endres, the private nurse of a first-class passenger, survived.
      The familiar story of the sinking of the ship should not overshadow the personal
      tragedies, that still resonate with many families today.

PMID- 22594202
TI  - How to tackle the taboo.

PMID- 22594203
TI  - Introduction to patient safety series.

PMID- 22594204
TI  - The importance of applying human factors to nursing practice.
AB  - The aim of this series is to introduce the topic of human factors and to show how
      it can be used in nursing practice on the ward and in nursing management, to
      improve the safety of patient care. Human factors can be used to make many
      aspects of working life easier, and if it is easier to do it is less likely to go
      wrong. This article discusses the importance of human factors in nursing and
      provides some practical suggestions on how to apply the principles of human
      factors. Forthcoming articles will examine human factors tools, surgical safety
      and human reliability in more detail.

PMID- 22594206
TI  - Faecal incontinence.

PMID- 22594205
TI  - Management of patients with asthma and allergic rhinitis.
AB  - Asthma and allergic rhinitis are two of the most common manifestations of
      allergy. The conditions have similar aetiologies, and genetic and environmental
      influences. There is increasing evidence that asthma and allergic rhinitis
      frequently co-exist, this article discusses the pharmacological management of
      these conditions, whether they exist independently or simultaneously. Correct use
      of inhaler devices and nasal sprays is also outlined.

PMID- 22594207
TI  - Pain management during wound dressing in children.
AB  - This article reviews the literature describing pharmacological and non
      pharmacological strategies that nurses can use to manage pain during wound
      dressing in children aged between one and 18 years in cases where general
      anaesthesia is not required. The article discusses the assessment of wound pain
      and anxiety in children and describes the choices available to nurses when
      managing pain and anxiety during wound dressings.

PMID- 22594209
TI  - The road to independence.

PMID- 22594208
TI  - Best practice in the management of venous leg ulcers.
AB  - Leg ulcers are wounds or open sores, often chronic in nature (long-lasting and
      non-healing), which cause damage to the skin. Appropriate management of chronic
      venous leg ulcers is essential to prevent further deterioration of the wound,
      improve patients' quality of life and reduce any healthcare costs associated with
      treating complications of such ulcers, including infection. However, management
      of leg ulcers can be challenging, particularly in patients who do not adhere to
      treatment regimens, cannot tolerate compression therapy, or have increased pain
      and infection. This article aims to identify best practice in the management of
      venous leg ulcers.

PMID- 22594210
TI  - 'We are achieving what families want'.

PMID- 22594211
TI  - Openness and honesty.

PMID- 22594212
TI  - Approaches used by employee assistance programs to address perpetration of
      intimate partner violence.
AB  - Employee Assistance Programs (EAPs) are workplace resources available to
      employees with problems impacting work performance. EAPs are well-positioned to
      address intimate partner violence (IPV), a major public health problem with
      workplace impacts. A purposeful sample of 28 EAPs across the United States was
      surveyed to identify policies and programs to address IPV, including
      perpetration. Most EAPs did not report having standardized approaches for
      addressing IPV perpetration. EAPs also described significant barriers to
      identifying IPV perpetrators, with the majority relying on self-disclosure on the
      part of the perpetrator when contacting the EAP. These results suggest that many
      EAPs--even when interacting with employees who present with issues known to
      correlate with IPV--are missing a potential opportunity to assess and intervene
      with IPV perpetrators.

PMID- 22594213
TI  - Reactions to resistance: the role of contextual factors in sex offending.
AB  - Upon encountering victim resistance during the commission of a sexual assault, an
      offender makes a decision as to how to react to the resistance via the use of
      varying degrees of coercive or noncoercive tactics. Exhaustive chi-squared
      automatic interaction detection (CHAID) analyses were performed on a sample of
      369 criminal events to detect the significant situational and crime-specific
      factors, the pertinent interactions between these factors, and how these affect
      an offender's reaction to victim resistance depending on whether the victim is a
      child or an adult. Findings show that multiple interactions do occur and,
      moreover, factors affecting the offender's reaction to victim resistance are very
      different depending on whether the victim is a child or an adult. Planning and
      preparation variables, such as the offender's attack strategy, were found to be
      significant in the child victim model, whereas reactive variables, such as the
      type of victim resistance, were found to be significant in the adult victim
      model. The findings lend support to the social interac-tionist perspective and
      the importance of victim-offender dynamics.

PMID- 22594214
TI  - Youth violence in South Africa: exposure, attitudes, and resilience in Zulu
      adolescents.
AB  - Exposure to violence is common in South Africa. Yet, few studies examine how
      violence exposure contributes to South African adolescents' participation in
      youth violence. The aims of this study were to examine effects of different
      violence exposures on violent attitudes and behavior, to test whether attitudes
      mediated effects of violence exposures on violent behavior, and to test whether
      adult involvement had protective or promotive effects. Questionnaires were
      administered to 424 Zulu adolescents in township high schools around Durban,
      South Africa. Structural equation modeling (SEM) was used to test associations
      among violence exposures and both violent attitudes and behavior. Victimization,
      witnessing violence, and friends' violent behavior contributed directly to
      violent behavior. Only family conflict and friends' violence influenced violent
      attitudes. Attitudes mediated effects of friends' violence on violent behavior.
      Multiple-group SEM indicated that adult involvement fit a protective model of
      resilience. These findings are discussed regarding their implications for
      prevention.

PMID- 22594215
TI  - Examining the relationship between Latinas' perceptions about what constitutes
      domestic violence and domestic violence victimization.
AB  - Domestic violence is a serious issue for U.S. Latinas. Better understanding of
      the potential risk or protection that cultural perceptions about what constitutes
      domestic violence may convey can help strengthen interventions. Therefore, a
      convenience sample of 93 Latinas was surveyed about their current levels of
      domestic violence victimization, acculturation, and demographics, as well as
      about whether 5 behavioral scenarios constituted domestic violence. Hierarchical
      multiple regressions were performed to examine the relationships between the 5
      perception items and domestic violence victimization. After adjusting for
      established risk factors, only viewing male partner stalking and female verbal
      aggression as domestic violence were significantly associated with decreased
      domestic violence victimization. Findings can be integrated into the development
      and implementation of culturally competent interventions targeting Latinas.

PMID- 22594216
TI  - College women's perceived risk to experience sexual victimization: a prospective
      analysis.
AB  - This study implemented a prospective design to explore college women's perceived
      risk to experience sexual victimization over a 2-month interim (N = 143).
      Compared to women without such histories, women with a history of unwanted sexual
      contact via arguments/ pressure, or a history of unwanted sexual intercourse via
      administration of alcohol/drugs reported higher perceived risk to subsequently
      experience these forms of victimization. Compared to women who were not
      victimized, women who subsequently experienced unwanted sexual intercourse via
      administration of alcohol/drugs or arguments/pressure reported higher levels of
      risk to experience these forms of victimization. Controlling for victimization
      history, higher levels of risk to experience sexual intercourse over the interim
      via arguments predicted this form of victimization over the follow-up.
      Implications are discussed.

PMID- 22594217
TI  - Dating violence: mental health consequences based on type of abuse.
AB  - This study aims to determine the relationship between psychological, physical,
      and sexual abuse, and mental health symptoms. Female college students (N = 499)
      completed anonymous online surveys to report experiences of abuse, as well as
      symptoms of depression, posttraumatic stress disorder (PTSD), and physical
      injuries. Five groups of participants were found: no abuse; psychological abuse;
      physical abuse; psychological and physical abuse; and psychological, physical,
      and sexual abuse. The multiple abuse groups showed the highest rate of mental
      health symptoms. In addition, increased frequency of abuse was related to more
      mental health symptoms and more physical injuries.

PMID- 22594218
TI  - Gender differences in attitudinal acceptance of intimate partner violence
      perpetration under attachment-relevant contexts.
AB  - Attachment theory has been one of the leading theoretical frameworks in the last
      few decades for explaining physical violence within romantic relationships. In
      this study, the authors examined differences in attachment patterns and
      attitudinal acceptance of violence perpetrated in romantic relationships among
      men and women. The Attitudinal Acceptance of Intimate Partner Violence
      questionnaire was developed to measure acceptance of intimate partner violence
      (IPV) under attachment-relevant contexts of abandonment, as well as other
      contexts identified in the literature. Results indicated that men with higher
      degrees of attachment anxiety were more accepting of both male- and female
      perpetrated IPV under contexts of abandonment, and men with higher degrees of
      attachment avoidance were more accepting of female-perpetrated IPV under contexts
      of abandonment. Implications for research and treatment are discussed.

PMID- 22594219
TI  - Secondary victims of rape.
AB  - Rape is often a very traumatic experience, which affects not only the primary
      victim (PV) but also his/her significant others. Studies on secondary victims of
      rape are few and have almost exclusively studied male partners of female rape
      victims. This study examined the impact of rape on 107 secondary victims,
      including family members, partners, and friends of male and female rape victims.
      We found that many respondents found it difficult to support the PV and that
      their relationship with the PV was often affected by the assault. Furthermore,
      the sample showed significant levels of traumatization, and it was estimated that
      approximately one quarter of the respondents suffered from posttraumatic stress
      syndrome (PTSD). Degree of traumatization was associated with a more recent
      assault, higher efforts to support the PV, recurrent thoughts about having been
      able to prevent the assault, a lack of social support for the respondent, and
      feeling let down by others. The respondents were generally interested in friend-,
      family-, and partner-focused interventions, particularly in receiving education
      about how best to support a rape victim.

PMID- 22594220
TI  - Police interviews of sexual assault reporters: do attitudes matter?
AB  - Sexual assault is underreported in the United States. Survivors are often
      reluctant to make police reports for various reasons; one is fear of
      revictimization by criminal justice professionals. Conversely, police officers
      often lack skills for interviewing crime victims. Posttraumatic stress reactions
      among victims can exacerbate the problem. Although some victims prefer female
      interviewers, it is not known whether they are more skilled. A sample of 429
      police officers completed a written survey testing their rape myth acceptance and
      knowledge of how to interview rape reporters. A significant relationship between
      rape myth acceptance and interviewing skill was discovered. Although officer
      gender was related to interviewing skill, the effect was mediated by rape myth
      acceptance. Specific officer behaviors related to high rape myth acceptance were
      identified. Implications for selection of police to conduct victim interviews
      were discussed.

PMID- 22594221
TI  - Examining the nexus between domestic violence and animal abuse in a national
      sample of service providers.
AB  - Companion animals play a complex role in families impacted by violence. An outlet
      of emotional support for victims, the family pet often becomes a target for
      physical abuse. Results from a comprehensive e-survey of domestic violence
      shelters nationwide (N = 767) highlight both improvements and existing gaps in
      service provision for domestic violence victims and their pets. Quantitative and
      qualitative data noted frequently encountered obstacles to successful shelter
      seeking by abuse victims with companion animals including a lack of availability,
      funding, space, and reliable programming. Although results indicate an overall
      improvement in organizational awareness, fewer than half of surveyed shelters
      include intake questions about animals. Continued awareness and an expansion of
      services is needed to create viable safety planning strategies and reliable
      alternatives for women with companion animals in order to improve the likelihood
      that abuse victims will seek escape and refuge for themselves, their children,
      and their pets.

PMID- 22594222
TI  - [The thinking and design techniques for Chinese cleft lip nasal deformity].
AB  - Cleft lip nasal deformity reconstruction is one of the difficult points of cleft
      palate sequence treatment. Treatment principle and method of cleft nasal
      deformity is mainly from the western scholars' point of view and technology. In
      this paper, according to the differences of typical form of east and west, we
      proposed the reconstructive theory and method corresponding to the Chinese. We
      hope that can deepen our understanding to the nasal deformity and the
      characteristics of cleft lip in order to improve reconstructive method.

PMID- 22594223
TI  - [The construction and expression of Saccharomyces albicans pACT1-GFP plasmids].
AB  - OBJECTIVE: To construct strains containing green fluorescent protein (GFP) to
      study gene regulation in Saccharomyces albicans cells during the infection
      process. METHODS: pACT1-GFP was constructed, and Saccharomyces albicans CAI4 was
      transformed. The expression of GFP in yeast and hyphal compartments was observed
      with microscopy. RESULTS: 99% of Saccharomyces albicans cells containing pACT1
      GFP fusion displayed significant fluorescence levels both in the yeast and hyphal
      compartments. The fluorescence intensity in two compartments had no obvious
      difference. CONCLUSION: pACT1-GFP can be expressed stably in the yeast cells.

PMID- 22594224
TI  - [Effect of gradually induced disordered occlusion on the expression of
      osteoprotegerin and receptor activator of nuclear factor-kappaB ligand in
      mandibular condylar cartilage of rats].
AB  - OBJECTIVE: To investigate the effect of gradually induced disordered occlusion
      (GIDO) on the expression of osteoprotegerin (OPG) and receptor activator of
      nuclear factor-kappaB ligand (RANKL) in mandibular condylar cartilage of rats.
      METHODS: Totally 48 rats, aged 8 weeks were included, and were divided into
      experimental and control groups randomly at 4 time points, with same gender
      distribution (n=3). By inserting elastic rubber band the right side mandibular
      first molar and the left side maxillary first molar were moved mesially. Four
      weeks later, the right side mandibular third molar and the left side maxillary
      third molar were moved distally with same method. In this way, the GIDO was
      established in rats. The rats were sacrificed at the end of 2th, 4th, 6th and 8th
      week respectively after the application of the GIDO. The expression of OPG and
      RANKL in condylar cartilage was examined with immunohistochemical method and
      calculated by the area of positive cell percentage. RESULTS: OPG and RANKL
      expressed predominantly in condylar cartilage hypertrophic layer. The rats in
      experimental group expressed a higher OPG level in all of the 4 time points than
      their age-matched controls (P<0.05), while RANKL were higher in 2, 6, 8 weeks
      subgroups (P<0.05), but not in 4 weeks subgroup. No differences were found
      between male and female subgroups. CONCLUSION: The present results suggest that
      both OPG and RANKL take part in the condylar cartilage remodeling procedure in
      the present rat model.

PMID- 22594225
TI  - [Clinical application of mimics software in three dimensional CT images for
      treatment of zygomatic complex fracture].
AB  - OBJECTIVE: To study a reliable CT measuring method for quantitative diagnosis of
      unilateral zygomatic complex fracture and operation guiding. METHODS: 20
      zygomatic complex fracture patients needed operation were collected, three
      dimensional CT images of all patients were measured and analyzed by Mimics
      software before operation. Standard anatomy points of bilateral zygomatic complex
      and adjacent bone were selected, then the distance of two same selected points
      and the angles of three same selected points were measured by Mimics software.
      Compared to uninjured side, the different value of the distance and the angle of
      injured side zygomatic complex were acquired, zygomatic complex fractures were
      operated based on the different value. All patients were examined by three
      dimensional CT postoperatively, and the different value of the distance and the
      angle of both side were measured using same method to pre-operation. Therapy
      effects were analyzed based on the data of different value of the distance and
      the angle. RESULTS: 1) The displacement of zygoma of most patients was backward
      and inward. The different value of the distance between uninjured and injured
      side was less than 2 mm, and the different value of the angle was less than 1
      degrees. All patients reached the three-dimensional symmetric, surgical results
      were satisfactory in recovery of occlusion and mouth opening. 2) The zygomatic
      arch protrusion angle was about 138.50 degrees +/- 1.15 degrees, zygomatic
      prominent angle was about 132.72 degrees +/- 0.89 degrees. The two data were
      normal distribution. CONCLUSION: Three dimensional CT measurements of zygomatic
      complex can be achieved for the quantitative measurement of spatial displacement,
      and have directive significance for the reduction of the zygomatic complex
      fractures.

PMID- 22594226
TI  - [Three dimensional finite element analysis on stress distribution in dentin of
      the maxillary central incisor restored with different shapes and materials of
      post].
AB  - OBJECTIVE: To investigate the stress distribution in dentin of the maxillary
      central incisor restored with post-core which is related to different shapes and
      materials. METHODS: CT scan, digital-image processing and Unigraphics (UG)
      software were applied to construct the three-dimensional finite element models of
      maxillary central incisor restored with cone or column post-core. Based on this
      model, stress distribution of Von Mises in dentin with three different
      materials(polyethylene fiber resin, carbon fiber and zirconia) were analyzed
      respectively. Static loading(100N) was used on the lingual boundary line between
      upper-one-third and middle-one-third of maxillary central incisor, the direction
      of the loading was 45 degrees to the tooth long axis. RESULTS: In posts made of
      zirconia and restored with column post, the stress distribution in dentin was
      higher than with cone post (P<0.05). In posts made of polyethylene fiber resin or
      carbon fiber, there was no significant difference between the two post shapes
      (P>0.05). The elastic modulus of post-core materials affected the stress
      distribution, and the higher the elastic modulus was, the higher the stress
      concentrated. CONCLUSION: Cone post excels column post in higher elastic modulus
      materials. Using the lower elastic modulus materials possibly can avail to the
      stress distribution and prevent the root breakage. During the root canal
      preparation, the dentin around the root neck should be conserved as more as
      possible, especially the dentin in the labial side.

PMID- 22594227
TI  - [Effect of platelet rich plasma on the proliferation behavior of human MG63
      osteoblast-like cells in vitro].
AB  - OBJECTIVE: To assess the effect of platelet rich plasma (PRP) on proliferation
      and differentiation of human MG63 osteoblast-like cells and the biological
      function of PRP in vitro. METHODS: PRP was obtained from venous blood of a health
      volunteer by two step centrifugation. CaCl2 and thrombin were used to activate
      PRP. The differentiation of MG63 cells, which were exposed to various
      concentrations of PRP (0, 1%, 2%, 3%) was detected by alkaline phosphatase (ALP)
      activity. Propidium iodide (PI) fluorescent coloration staining was used to
      observe the morphology of cells. Immunocytochemistry was used to evaluate the
      expression level of transforming growth factor-beta (TGF-beta) in MG63 cells in
      different concentration of PRP. The cells adhered to calcium phosphate material
      was observed by scanning electron microscopy (SEM). The proliferation was
      evaluated by cell counting kit-8 (CCK-8) proliferation assay. The cell cycle
      assay was performed by low cytometry (FCM) to detect the effect of PRP on MG63
      cells in different time points. The mRNA level of Col-I in MG63 cells cultured
      under different concentration PRP was checked by reverse transcription polymerase
      chain reaction (RT-PCR). RESULTS: ALP activity experiment demonstrated that the
      maximum effect was got in 3% PRP group. PRP had a positive effect on the
      proliferation of MG63 cells but cells also presented disengage phenomena from the
      glass slides. The PI staining showed that PRP improved fluorescent intensity of
      cell nucleus. Immunocytochemistry showed that TGF-beta expression level was
      significantly enhanced on 3% PRP group (P<0.05). SEM showed that cells grew well
      on material in PRP group. The results of CCK-8 showed that the mean absorbency
      number A(450 nm) of 4.8% PRP was significantly higher than that of control group
      (P<0.05). FCM showed that S period cells percentage of PRP group was higher than
      that of control group in the 2nd day (P<0.05); G0/G1 period cells percentage of
      PRP group was significant increased than that of control group in the 10th day
      (P<0.05); G2/M period cells percentage of PRP group was higher than that of
      control group except the 6th day. PRP promoted the expression of Col- I in MG63
      cells by RT-PCR. CONCLUSION: These data suggest that PRP has a positive influence
      on MG63 proliferation, transference and the expression of relative protein and
      gene in an appropriated concentration. The findings of this study also
      demonstrated that PRP may play a beneficial role of unifying and modulating the
      biological behavior of MG63 cells.

PMID- 22594228
TI  - [Synthesis and evaluation of a novel injectable and water-swelling gingival
      displacement materials].
AB  - OBJECTIVE: To synthesize and evaluate a novel injectable and water-swelling
      gingival displacement materials. METHODS: A kind of water-swelling polymer,
      kaolin and aluminum chloride were mechanically mixed at certain ratio in water
      solution, resulting to a novel paste materials for gingival displacement. Then,
      its stability in aqueous solution and water swelling properties were evaluated in
      vitro. The effect on gingival displacement was evaluated by animal experiments in
      dogs. A commercial gingival displacement materials paste of Expasyl was used as
      control. RESULTS: While contacting with water, the novel gingival displacement
      paste did not collapse, maintained its integrity structure, and could expand for
      adsorbing water. Animal experiments in dogs showed that the materials could lead
      to displace the gingival margins from the dental root surfaces. CONCLUSION: The
      novel injectable and expanded gingival displacement material is efficient to
      retract free gingival margin with potential clinical application.

PMID- 22594229
TI  - [The effect of extraction and non-extraction decompensation to bimaxillary
      orthognathic surgery in skeletal class III malocclusion].
AB  - OBJECTIVE: To evaluate the effect of extraction and non-extraction decompensation
      to bimaxillary orthognathic surgery in skeletal class III malocclusion and the
      effect on postoperative. METHODS: Records of 36 completed surgical-orthodontic
      treatment skeletal class III malocclusion patients were obtained from School of
      Stomatology, China Medical University, 18 underwent maxillary premolar
      extraction, the other 18 underwent non-extraction. Their post-decompensation and
      postsurgery cephalometric radiographs were analyzed objectively, and their
      profile scissors-shadows in different groups were evaluated subjectively.
      RESULTS: The cephalometric index of post-presurgical orthodontics showed that
      there were significant deviations between the extraction and non-extraction
      groups including U1-SN, Overjet and Cm-Sn-UL values (P<0.05). During surgery,
      mandible was retruded (8.66 +/- 1.42) mm in extraction group compared with (6.21
      +/- 3.06) mm in non-extraction group (P<0.05). After surgery, the extraction
      group achieved more normal ANB, U1-SN, NA-PA values (P>0.05). CONCLUSION:
      Maxillary premolar extraction can make incisor decompensation more complete so
      that mandible can be retruded to more ideal position and concave face can be
      successfully corrected.

PMID- 22594230
TI  - [Comprehensive study on clinic presentation, radiology and pathology of recurrent
      ameloblastoma].
AB  - OBJECTIVE: To study the clinic presentation, radiology, pathology of recurrent
      ameloblastoma (RAB). METHODS: All RAB cases accepted treatment in School of
      Stomatology of Nanjing University during 1996.1-2008.3 were retrospected. The
      clinic presentation, the radiological classification and pathological
      classification were summarized and analyzed. RESULTS: There were 23 RAB patients
      during 1996.1-2008.3. 3 patients recurred twice, 20 patients recurred once, and
      26 cases were found together. 19 patients were performed conservative surgery
      while 4 patients were performed radical surgery in the primary treatment; 4
      patients were performed conservative surgery and 19 patients were performed
      radical surgery in the recurrence. The radiological classification included 12
      cases multicystic, 6 cases unicystic, and 8 cases extraosseous. The pathological
      classification included 21 cases follicular ameloblastoma, and 5 cases plexiform
      ameloblastoma. The multicystic after conservative surgery (11 cases) and
      extraosseous ameloblastoma after radical treatment (8 cases) were more than
      others according the radiological classification and treatment. CONCLUSION:
      Conservative surgery has apparent higher recurrences rate than radical surgery.
      The follicular ameloblastoma has more aggressive biological behave and is more
      liable to recurred.

PMID- 22594231
TI  - [CT morphology of mandibular bone and mandibular nerve canal in hemimandibular
      elongation].
AB  - OBJECTIVE: To study morphology feature of mandibular anatomical characteristics
      and mandibular nerve canal of hemimandibular elongation (HE) using CT, and
      provide reference for the clinical treatment. METHODS: 19 patients with HE were
      scanned using multidetector CT. Mimics 10.0 software was used for three
      dimensional reconstruction, and CT images were reconstructed on different
      sections. The position of mandibular nerve canal, mandibular foramen and
      thickness of mandibular cortical bone were measured, and compared with control
      group (without mandibular lesion). RESULTS: Compared with the control group, the
      distance between mandibular nerve canal and mandibular surface were statistically
      different at the section of long axis of mandibular first molar centre (LAMFM)
      lingual, long axis of mandibular second molar centre (LAMSM)-buccal, LAMSM
      superior, retromolar area centre to the mandibular angle (RAC-MA)-buccal, RAC-MA
      superior, RAC-MA-inferior and horizontal level of mandibular foramen under 5 mm
      (HLMFU5)-lingual, HLMFU5-anterior, HLMFU5-posterior (P<0.05); the thickness of
      mandibular cortical bone were statistically different at the LAMFM-buccal, LAMFM
      inferior (P<0.05); lowest point of mandibular foramen (LPMF)-superior border of
      mandibular ramus (SBMR) and LPMF-inferior border of mandibular ramus (IBMR) were
      statistically different (P<0.05). CONCLUSION: In the patients with hemimandibular
      elongation, the thickness of mandibular cortical bone gradually decreases in all
      directions from the mandibular first molar to the mandibular ramus. Compared with
      the control group, mandibular nerve canal located buccally and superiorly at
      mandibular second molar and retromolar area, mandibular foramen located more
      anterior and lower inside mandibular ramus.

PMID- 22594233
TI  - [The clinical study on the use of diode laser irradiation in the treatment of
      periodontal-endodontic combined lesions].
AB  - OBJECTIVE: To evaluate the adjunctive effect of diode laser irradiation for the
      treatment of periodontal-endodontic combined lesions. METHODS: 30 cases with
      periodontal-endodontic combined lesions were selected. All cases were randomly
      divided into experimental group and control group (n=15). In the control group,
      patients were treated with root canal therapy and conservative periodontal
      treatment (scaling and root planning), and patients in the experimental group
      were treated with root canal therapy and conservative periodontal treatment
      followed by diode laser irradiation. Clinical measurements including pocket
      probing depth (PPD), clinical attachment level (CAL), modified bleeding index
      (mBI), periapical index (PAI) were taken before treatment (baseline). Three and
      six months after the treatment, the adjunctive effects of diode laser in the
      treatment of periodontal-endodontic combined lesions were evaluated. RESULTS:
      Three months after the treatment, the average PPD, CAL and mBI levels were
      reduced significantly in both groups. But the average PPD reduction in the
      experimental group was significantly greater (P<0.05) than in control group.
      However the average CAL and mBI reduction were not significantly different
      between two groups. Six months after the treatment, the average PPD, CAL and mBI
      levels were further reduced in the experiment group, but not in the control
      group. The average PAI levels were reduced significantly in both groups, but the
      PAI reduction was not significantly different between two groups. CONCLUSION: The
      use of diode laser as an adjunct procedure in the treatment of periodontal
      endodontic combined lesions can aid in achieving success.

PMID- 22594232
TI  - [Research about the safe zone of microscrew implant insertion for back teeth by
      cone beam computed tomography].
AB  - OBJECTIVE: To measure the mesiodistal and buccolingual alveolar bone mass of back
      teeth in posterior alveolar crest at different height by cone beam computed
      tomography (CBCT), and analyze the safe area of microscrew implanted at back
      teeth in posterior alveolar crest. METHODS: 30 cases of adult scan image data
      were selected for the study of jaw bones scan reconstruction. From the distal of
      first premolar backward, buccolingual (plate) width and the mesiodistal size
      between each interfurcal region (including tuber maxillae) were measured from
      alveolar crest at top of 2, 4, 6, 8, 10mm. ANOVA and LSD methods were made by
      SPSS 16.0 software for comparison. RESULTS: 1) The mesiodistal bone mass of back
      teeth in maxilla at the same height with different position had statistically
      significant difference (P<0.05). The biggest mesiodistal bone mass was located at
      the palatal roots between the second premolar and the first molar. The
      statistically significant difference of buccolingual bone mass also existed at
      different position and height (P<0.05). The biggest buccolingual bone mass was
      located at the middle of the first molar and the second molar. 2) The mesiodistal
      bone mass of back teeth in maxilla at different height and position had
      statistically significant difference (P<0.05). The statistically significant
      difference of buccolingual bone mass also existed in the same position with
      different height (P<0.05). The biggest mesiodistal and buccolingual bone mass was
      located at the middle of the first molar and the second molar. CONCLUSION: The
      safe area of microscrew implanted at back teeth in posterior alveolar crest is
      tested by CBCT, which provides valuable reference for the follow-up clinical
      application.

PMID- 22594234
TI  - [A prospective follow-up study on the impact of urinary excretions of nickel and
      chromium after dental restoration by nickel-chromium based alloys].
AB  - OBJECTIVE: To explore whether the dental restoration of nickel-chromium (Ni-Cr)
      based alloys will lead to extra excretions of urinary Ni and Cr. METHODS: Urinary
      Ni and Cr were repeatedly measured in 33 patients before and 2 months after the
      dental restoration of Ni-Cr alloys. The associations between alloy restoration
      and urinary Ni or Cr were analyzed by paired t test and general linear model of
      repeated measures. RESULTS: A slightly higher urinary Ni was found in patients
      after 2 month of the alloy restoration, but the difference was not statistically
      significant (before: 46.4 microg x mol(-1) crea; after: 67.6 microg x mol(-1)
      crea; P=0.063). This difference was only in female subjects (before: 44.8 microg
      x mol(-1) crea; after: 73.7 microg x mol(-1) crea; P=0.068). A significant higher
      urinary Cr was found in patients after 2 month of the alloy restoration (before:
      57.0 microg x mol(-1) crea; after: 99.4 microg x mol(-1) crea; P=0.024). This
      significant difference was only in female subjects (before: 59.8 microg x mol(-1)
      crea; after: 124.4 microg x mol(-1) crea; P=0.023). General linear models of
      repeated measurements showed that urinary excretions of Ni and Cr were associated
      with the number of restoration and the area of metal basis uncovered with
      porcelain. CONCLUSION: Dental restoration of Ni-Cr alloy might lead to the
      enhanced excretions of urinary Ni and Cr.

PMID- 22594235
TI  - [Diagnostic accuracy of orthopantomogram and periapical film in evaluating root
      resorption associated with orthodontic force].
AB  - OBJECTIVE: To test the diagnostic accuracy of qualitative and semi-quantitative
      evaluations on root resorption associated with orthodontic force (RRAOF) using
      orthopantomogram (OPG) and periapical film, through comparing with assessments
      with cone beam computed tomography (CBCT), which is considered as the gold
      standard. METHODS: Before and after treatment, OPG, periapical film, CBCT images
      of 121 upper anterior teeth in 32 orthodontic patients were obtained. Blind
      evaluation of RRAOF was performed according to Levander and Malmgren's method by
      three trained radiographers through examining three kinds of images of these
      teeth. The diagnostic accuracy of qualitative and semi-quantitative evaluations
      on RRAOF using OPG and periapical films were test through comparing with
      assessments with CBCT, which was considered as the gold standard. RESULTS: To the
      same sample, the RRAOF qualitative and semi-quantitative diagnostic
      classification results of OPG and periapical films compared with CBCT were
      significant differences (P<0.05). The sensitivity of periapical films and OPG was
      71.6% and 78.4%. The specificity of periapical films and OPG was 25.5% and 51.1%.
      The accuracy of periapical films and OPG was 53.7% and 67.8%, respectively.
      CONCLUSION: Periapical films and OPG for evaluating RRAOF have a poor diagnostic
      accuracy.

PMID- 22594236
TI  - [Application of risk management in nursing management of head and neck oncology].
AB  - OBJECTIVE: To study the effect of risk management in nursing management of head
      and neck oncology. METHODS: In 2010, risk management was applied to the nursing
      management of head and neck oncology through risk identification, increasing
      awareness of risk management, defining risk management responsibilities,
      strengthening the capacity of specialist nurses and emergency response, and
      strengthening risk control measures. Patients' satisfaction, care complaints,
      nursing risk occurrence, nurse praised visits between 2009 and 2010 were
      compared. RESULTS: There were significant differences comparing 2009 with 2010 in
      patient satisfaction, care complaints, nursing risk occurs, nurse praised visits
      in head and neck oncology (P<0.05). CONCLUSION: Application of risk management in
      nursing management will relieve care complaints and nursing risk occurrences,
      improve patients' satisfaction. It is worth to further promote in the clinical
      nursing management.

PMID- 22594237
TI  - [The effect of premolar extraction models on Bolton overall ratio among different
      classes of malocclusion].
AB  - OBJECTIVE: To investigate the effect of different premolar extraction models on
      postextraction Bolton overall ratio among different classes of malocclusion.
      METHODS: 180 patients with equivalent skeletal and dental classifications were
      chosen(Group I, II and III, with 60 per group). According to dental casts, the
      Bolton overall ratios of each group were measured and compared before and after
      hypothetical premolar extraction (the four premolar extraction models were all
      first premolars, all second premolars, upper first and lower second premolars,
      and upper second and lower first premolars). Chi-square Test analysis was taken
      within each group in order to compare the abnormal rates of postextraction Bolton
      overall ratios. RESULTS: The differences of pretreatment Bolton overall ratios
      among three types of malocclusions were found statistically significant
      (P=0.000). For Class I and Class II group, the four extraction models made no
      statistically significant differences in the abnormal rates of postextraction
      Bolton overall ratio (P>0.05). For Class III group, the four extraction models
      made statistically different results that was the upper second and lower first
      premolar extraction model creating lower abnormal rates than the upper first and
      lower second premolar extraction model (P=0.002). CONCLUSION: As far as the
      postextraction Bolton overall ratios are concerned, Class I and II malocclusions
      can choose any of four premolar extraction models, while to Class III
      malocclusions, the upper second and lower first premolar extraction model fits
      better than the upper first and lower second premolar extraction model.

PMID- 22594238
TI  - [Application research of cone beam CT in dowel preparation for the mandibular
      first molar].
AB  - OBJECTIVE: To measure the root anatomic topography of mandibular first molar
      using cone beam CT (CBCT), calculate the proper space for dowel preparation.
      METHODS: The roots of 121 mandibular first molars from 71 patients were scanned
      by CBCT, the images from cross section, sagittal plane, and coronal plane were
      got respectively. The dowel preparation spaces according to established three
      dimensional images and dowel preparation requirements were analyzed. RESULTS:
      Three dowels could be prepared. The dowel length for distal-root was (7.19 +/-
      0.91) mm, dowel diameter was (0.80 +/- 0.12) mm on the level of 4mm above root
      apex. The dowel length for mesio-root was (6.92 +/- 1.02) mm, and dowel diameter
      was (0.71 +/- 0.08) mm on the lever of 4 mm above root apex for buccal side and
      (0.71 +/- 0.07) mm for lingual side. Dowel should be prepared cone-shaped.
      CONCLUSION: Many factors affect dowel preparation, individualized design is
      needed. CBCT can provide reliable radiographic evidence.

PMID- 22594239
TI  - [The primary study on the gene expression profiles of alveolar bone with
      traumatic occlusion in early stage in rats].
AB  - OBJECTIVE: To study the gene expression profiles of traumatic occlusion in early
      stage with the animal model of rats. METHODS: The occlusal surface of the upper
      left first molar of rat was raised by placing a stainless steel wire to induce
      occlusal trauma in the lower left first molar. After 24 hours, the alveolar bone
      tissue of the first molars at the both sides of rats' lower jaws were taken out
      under anesthesia. The different expressive genes were shown by genome-wide
      microarray, which comprises about 27 000 genes and analyzed the different
      expressive genes with Pathway and GO analysis, finally the results of the
      microarray were examined by real time-polymerase chain reaction (RT-PCR).
      RESULTS: In the results of the study, 586 different expressions were found, of
      which the expressions of 166 genes increased and 420 genes decreased. 106
      different pathways were involved with Pathway analysis and 270 different
      functional classification related to GO analysis. CONCLUSION: The balance of the
      lower alveolar bone is destroyed after 24 hours of traumatic occlusion. At early
      phase of the occlusal trauma, osteogenesis and bone formation in alveolar bone
      are inhibited, yet osteoblast genesis and bone resorption are not significant.

PMID- 22594240
TI  - [Correlation between smoking and the polymorphisms of cytochrome P450 1A1-Msp I
      and glutathione S-transferase T1 genes and oral cancer].
AB  - OBJECTIVE: To investigate the correlation between the combination of smoking and
      the polymorphisms of cytochrome P450 (CYP) 1A1-Msp I and glutathione S
      transferase (GST) T1 genes and oral cancer. METHODS: The genetic polymorphisms of
      CYP1A1-Msp I and GSTT1 were detected by polymerase chain reaction (PCR) technique
      in peripheral blood leukocytes of 300 oral cancer cases and 300 non-cancer
      controls, and the correlation between smoking, the two metabolic enzymes genetic
      polymorphisms and oral cancer were analyzed. RESULTS: The frequencies of CYP1A1
      Msp I (m2/m2) and GSTT1(-) were 38.33% and 69.33% in oral cancer cases and 21.00%
      and 44.33% in healthy controls respectively. Statistical tests showed significant
      difference in the frequencies between the two groups (P<0.01). The risk of oral
      cancer with CYP1A1-Msp I (m2/m2) was significantly higher than that of controls
      (OR= 2.34, 95%CI 1.76-4.07). The individuals who carried with GSTT1(-) had a high
      risk of oral cancer(OR=2.84, 95% CI 1.98-4.54). Combined analysis of the
      polymorphisms showed that percentage of CYP1A1-Msp I (m2/m2)/GSTT1(-) in oral
      cancer and control groups was 30.67% and 6.67% respectively (P<0.01). The people
      who carried with CYP1A1-Msp I (m2/m2)/GSTT1(-) had a high risk of oral
      cancer(OR=8.27, 95%CI 3.63-11.29). The smoking rate of the case group was
      significantly higher than that in the control group (OR=2.71, 95%CI 1.31-4.52,
      P<0.01), and statistic analysis suggested an interaction between smoking and
      CYP1A1-Msp I (m2/m2)/GSTT1(-) genotypes polymorphisms which increased risk of
      oral cancer (OR=25.00, 95%CI 11.87-35.64). CONCLUSION: CYP1A1-Msp I (m2/m2) and
      GSTT1(-) are the risk factors in oral cancer. Smoking is also related to the
      susceptibility to oral cancer. There may be a synergetic interaction among CYP1A1
      Msp I (m2/m2), GSTT1(-) and smoking on the elevated susceptibility of oral
      cancer.

PMID- 22594241
TI  - [Construction PG0839 gene-defective mutant of Porphyromonas gingivalis].
AB  - OBJECTIVE: In order to determine the function of PG0839 gene from Porphyromonas
      gingivalis (P. gingivalis) W83 strains, we intended to create a mutant in the
      PG0839 gene by homologous recombination. METHODS: 1 584bp PG0839 gene fragment
      was amplified, digested by BamH I and EcoR I, purified and ligated to pUC19. The
      recombinant plasmid was designated as pPG0839-1. The erm cassette (2 101 bp) was
      inserted into the EcoR V restriction site of the PG0839 gene. The resultant
      recombinant plasmid, pPG0839-2, was used as a donor in the electroporation of P.
      gingivalis W83. After electroporated and selected on erythromycin brain heart
      infusion plates, a single colony was collected and designated as PG0839 gene
      defective mutant. RESULTS: A mutant in PG0839 gene was created by insertional
      inactivation, and inactivation of PG0839 gene was confirmed by restriction
      endonuclease digestive, sequencing, polymerase chain reaction (PCR) and reverse
      transcription PCR. CONCLUSION: A PG0839 gene-defective mutant was created
      successfully.

PMID- 22594242
TI  - [A study on the application of the perceptual assessment in the diagnosis of the
      velopharyngeal function].
AB  - OBJECTIVE: To investigate the application of the perceptual assessment in the
      diagnosis of the velopharyngeal function, to provide a reference to the
      improvement of the velopharyngeal function diagnosis through comparing the
      consistency between the diagnosis of the perceptual assessment and the objective
      assessment. METHODS: All subjects (254) were selected from the Department of
      Cleft Lip and Palate Surgery, West China School of Stomatology, Sichuan
      University, from 2000-2010. The results of the perceptual and the nasopharyngeal
      fiberscope (NPF) assessment were retrospectively analyzed, and the consistent
      rate between the two assessment methods was calculated. The Kappa test and the
      correlation analysis were performed to analyze the consistency and correlation,
      and the factors relating to the perceptual assessment were analyzed by the
      correlation coefficient. RESULTS: There were 254 patients met the inclusion
      criteria. The consistent number of the patients diagnosed by the perceptual and
      the objective assessment as velopharyngeal competence (VPC) and velopharyngeal
      insufficiency (VPI) were 58 and 167 respectively. The consistent rate was 88.58%
      for all patients, and 66.67% for the VPC patients. The Kappa value was 0.721,
      Spearman's R=0.751, P<0.05. There were correlation between the hypernasality, the
      nasal emission and the subjective assessment, and Spearman's R=0.697, 0.590,
      P<0.05. CONCLUSION: The VPC patients and the VPI patients with moderate and
      severe hypernasality and nasal emission diagnosed by the perceptual assessment
      could be exempt from the objective examination. Patients diagnosed with mild
      hypernasality and nasal emission by the perceptual assessment should be further
      referred to NPF or other instruments.

PMID- 22594243
TI  - [Study of antibacterial effect of polymethyl methacrylate resin base containing
      Ag-TiO2 against Streptococcus mutans and Saccharomyces albicans in vitro].
AB  - OBJECTIVE: To study the antibacterial effect of polymethyl methyacrylate (PMMA)
      resin base containing Ag-TiO2 antibacterial agent against common conditioned
      pathogen and their bacterial plaque in vitro. METHODS: Different qualities of Ag
      TiO2 antibacterial agent were added into PMMA resin base in order to prepare
      antibacterial PMMA resin base. Then, in vitro analysis of antibacterial effect of
      the resin base against Streptococcus mutans, Staphylococcus aureus, Saccharomyces
      albicans were assayed with the pellicle-sticking method. Furthermore, the growth
      of Streptococcus mutans and Saccharomyces albicans bacterial plaque on the
      antibacterial PMMA resin base were examined by scanning electron microscope.
      RESULTS: The inhibition percent for Staphylococcus aureus was 93.3% by
      antibacterial PMMA resin base with 0.7% Ag-TiO2; for Streptococcus mutans 90.2%
      with 1.5% Ag-TiO2; for Saccharomyces albicans 91.2% with 2.5% Ag-TiO2. Bacterial
      plaque of Streptococcus mutans and Saccharomyces albicans on antibacterial resin
      base were inhibited effectively. CONCLUSION: The antibacterial property of the
      PMMA resin base is effectively enhanced with Ag-TiO2 antibacterial agent.

PMID- 22594244
TI  - [The observation of surface morphology of enamal and temperature of dental pulp
      cavity in vitro after irradiated by Er:YAG laser].
AB  - OBJECTIVE: To observe the changes of surface morphology and temperature of dental
      pulp cavity in vitro after irradiated by Er:YAG laser with different energy and
      irradiation time. METHODS: All of the 96 samples from 24 teeth in vitro were
      collected from dental clinical departments then divided into two groups (group A
      and group B) randomly. We chose the energy of 20 Hz, and 1, 2, 3, 4, 5, 6 W to
      treat the samples in group A and group B and the irradiation time was 10s or 20s.
      We recorded the temperature changes of dental pulp cavity by digital thermometer
      and observe the morphology of tooth enamel by scanning electron microscope (SEM).
      RESULTS: With the extension of irradiation time and increasing of energy, the
      temperatures of dental pulp cavity were significantly increased after the
      treatment of Er: YAG laser. The two groups of tooth enamel surface morphology
      were changed after irradiated by Er: YAG laser with different energy and
      irradiation time. However, there was no melting and carbonation on the surface of
      tooth enamel after the treatment of Er:YAG laser in two groups. CONCLUSION: The
      temperatures of dental pulp cavity were increased after irradiated by increasing
      laser energy density fom 1 W to 6 W. No melting or carbonized phenomenon was
      found in enamel within the energy of 1 W to 6 W. All the data would provide
      evidences for clinical treatment of cavity.

PMID- 22594245
TI  - [Biocompatibility of porous calcium phosphate ceramic nanocomposite].
AB  - OBJECTIVE: To study the biocompatibility of porous calcium phosphate ceramics
      nanocomposite. METHODS: The biocompatibility was evaluated via experiments
      including the hemolysis test, hemopexis test, acute systemic toxicity test,
      pyrogen test, and intramuscular implant test, in which biphasic calcium phosphate
      nanocomposite (NanoBCP) presented as leaching solution, suspension or blocks of 5
      mmx5 mmxl mm. Animals including New Zealand Rabbits, Kunming mice, SD rats were
      selected as the host. RESULTS: The hemolysis of NanoBCP was 1.1% (<5%). Four
      coagulation index levels were within the normal range. In pyrogen test, the
      temperature of each experimental rat increased by 0.35, 0.40, 0.28 degrees C
      (<0.60 degrees C, in accordance with the pyrogen-free criterion for biomedical
      materials). No consequent death, dyspnoea, organ dysfunction, severe peritoneal
      irritation or ptosis was observed in acute systemic toxic test. Newly-formed
      fibrous tissue could be found after the implantation. CONCLUSION: The material
      possesses outstanding biocompatibility and degradability with no toxicity or
      irritation, contains no pyrogen, as well as better degradation properties than
      biphasic calcium phosphate.

PMID- 22594246
TI  - [Caries status of primary and permanent teeth among 6-year-old children in
      Sichuan province and their correlation].
AB  - OBJECTIVE: To investigate caries status of primary and permanent teeth among 6
      year-old children in Sichuan Province and correlation between caries of deciduous
      molars and first permanent molars. METHODS: Referenced to the sampling programme
      of the third national epidemiological survey of oral health status, a total of
      714 children aged 6 were randomly sampled in clusters including 3 urban sampling
      spots and 3 rural sampling spots, the correlation between caries of deciduous
      molars and first permanent molars was explored. RESULTS: The prevalence rate of
      deciduous tooth caries of 6-year-old children in Sichuan province was 74.37%, the
      mean number of dmft of 6-year-old was 3.94 +/- 3.93, the filling rate was only
      4.96%. The prevalence rate and mean dmft of deciduous tooth caries showed no
      significant difference between different area and gender (P>0.05), however, the
      children came from city showed significant higher filling rate than those from
      countryside (P<0.05). The first permanent molars erupted have 2.98% in caries,
      the filling rate was 7.69%. Caries of deciduous molars was the first permanent
      molars caries risk factors among 6-year-old children in Sichuan province
      [P=0.001, r=0.175, OR=5.756, 95%CI (1.733, 19.121)]. There was weak correlation
      between caries of deciduous molars and first permanent molars (P<0.001, r=0.194).
      CONCLUSION: Caries status of primary among 6-year-old children in Sichuan
      Province are serious. Caries experience of deciduous molars may play an important
      role in predicting the first permanent molars caries in clinic and prevention.

PMID- 22594247
TI  - [Mechanical properties of thermodynamic nickel-titanium archwires in a simulated
      oral environment in vitro].
AB  - OBJECTIVE: This study was to investigate the mechanical properties of
      thermodynamic nickel-titanium (NiTi) archwires of different brands under
      controlled temperature and in artificial saliva to provide some reference for its
      clinical application. METHODS: Using a modified partial dental arch bending
      system, four types of thermodynamic NiTi archwires were tested under controlled
      temperature (25, 33, 37, 60 degrees C) and in artificial saliva. An Instron
      Universal Testing Machine was used to apply 3 mm deflections of archwires in the
      lateral incisor area. The load-deflection curves were determined from the passive
      position to deflections of 3 mm. The following variables from unloading curves
      were calculated: Stiffness between 2.5 mm UDP (unloading deflection point) to 0.5
      mm UDP after unloading. Any statistically significant differences in these
      variables for the different brands, temperature and moments levels were analyzed
      using one-way analysis of variance. RESULTS: Unloading values of four types
      thermodynamic nickel-titanium archwires increased with controlled temperature
      rising. The unloading stiffness of the same brand archwires were approximate at
      25, 33, 37 degrees C, while their unloading stiffness increased obviously at 60
      degrees C. CONCLUSION: Different brands thermodynamic NiTi archwires demonstrated
      different mechanical behaviours, but all of them exhibited super elasticity and
      practical shape memory effect. The four thermodynamic NiTi archwires displayed
      temperature sensitivity at the four test temperatures.

PMID- 22594248
TI  - [Allergy caused by sodium fluoride glycerin: a case report].
AB  - In recent years, though more and more ulcerations of oral mucosa caused by
      allergy to drug occurred clinically, allergy to sodium fluoride glycerin is
      extremely rare. A case of allergy to sodium fluoride glycerin occurred in
      Qianfoshan Campus Hospital of Shandong University. After treatment by sodium
      fluoride glycerin, there was mucosal edema, a large number of red miliary
      granules in buccal and palatal mucosa. After 3 hours, there were swallowing
      difficulties, but no breathing difficulties. Next day large ulcers of oral mucosa
      developed. The patient was cured 7 days after treatment. Fluoride-sensitive test
      result was positive.

PMID- 22594249
TI  - [A gate spring which can torque an individual tooth with high efficiency].
AB  - It is to address torquing an individual tooth using a gate spring. The gate
      spring is made of a rectangular stainless steal wire, in the shape of a gate,
      which is incorporated to the archwire by spot welding. Torque is generated by the
      combined effects of the gate spring and the archwire. After 2-3 months, the gate
      spring can obviously torque individual tooth.

PMID- 22594250
TI  - UPLC: a preeminent technique in pharmaceutical analysis.
AB  - The pharmaceutical companies today are driven to create novel and more efficient
      tools to discover, develop, deliver and monitor the drugs. In this contest the
      development of rapid chromatographic method is crucial for the analytical
      laboratories. In precedent decade, substantial technological advances have been
      done in enhancing particle chemistry performance, improving detector design and
      in optimizing the system, data processors and various controls of chromatographic
      techniques. When all was blended together, it resulted in the outstanding
      performance via ultra-high performance liquid chromatography (UPLC), which holds
      back the principle of HPLC technique. UPLC shows a dramatic enhancement in speed,
      resolution as well as the sensitivity of analysis by using particle size less
      than 2 pm and the system is operational at higher pressure, while the mobile
      phase could be able to run at greater linear velocities as compared to HPLC. This
      technique is considered as a new focal point in field of liquid chromatographic
      studies. This review focuses on the basic principle, instrumentation of UPLC and
      its advantages over HPLC, furthermore, this article emphasizes various
      pharmaceutical applications of this technique.

PMID- 22594251
TI  - Evaluation of polyphenols and anthocyanins contents in black chockeberry-
      Photinia melanocarpa (Michx.) fruits extract.
AB  - An evaluation of total polyphenols and anthocyanins contents in dietary
      supplements is important analysis in medical aspect of human and animal diets.
      The content of the mentioned compounds should be higher in 100 g of solid
      extracts than in 100 g of fruits. Thus, the presented work concerns the
      evaluation of total polyphenols and anthocyanins contents in black chockeberry-
      Photinia melanocarpa (Michx.) extract--dietary supplement (DS) available on
      market. The spectrophotometric analysis of DS were performed. The usage of
      certain conditions of measurements such as dilution factor, storage conditions
      and filtration, has the significance in the determination of the analyzed
      compounds in the extract.

PMID- 22594252
TI  - First order derivative spectrophotometric and HPLC methods for determination of
      moexipril hydrochloride in the pure form, pharmeceutical formulations and
      evaluation of its stability.
AB  - A rapid, linear (over a concentration range of 0.00012-0.0012% and with
      correlation coefficient r = 0.999), accurate (an average recovery of 100%),
      precise (an average standard deviation < 1.5%) and economical first derivative UV
      spectrophotometric assay method (lambda(max) = 238 nm) was developed for the
      determination of moexipril hydrochloride (MOXL) in a pharmaceutical formulation.
      The method was investigated for its utility for the determination of MOXL in
      commercially available tablets and as a stability-indicative assay in solid
      state. The results obtained by means of the investigated method were
      statistically compared (t-Student test and F-Snedecor test) with the results
      obtained by means of the reference method--HPLC, which evidenced that both
      methods are equally precise and accurate. It was finally concluded that first
      derivative UV spectrophotometry is selective with reference to excipients used
      for the tablets' formulation, however, it is not selective with reference to MOXL
      degradation products.

PMID- 22594253
TI  - Determination of local anesthetics in illegal products using HPLC method with
      amperometric detection.
AB  - An HPLC method with amperometric detection was developed for analysis of two
      local anesthetics (lidocaine and benzocaine) in products for delaying ejaculation
      illegally marketed in Polish sex shops. Chromatographic elution on an RP column
      C18 with mobile phase composed of acetate buffer with acetonitrile, provides an
      optimal separation not only of active substances but also electroactive
      preservatives which are occasionally added to cosmetic creams (methylparaben and
      propylparaben). Application of glassy carbon electrode as a working electrode and
      a procedure with pulsed potential waveforms enables a sensitive, accurate
      measurement within a relatively short analysis time (250 s). This method has been
      successfully employed for the determination of local anesthetics in products
      under investigation. The obtained results show that most samples contained
      therapeutic concentrations of lidocaine or benzocaine. According to European law,
      a sale of products containing lidocaine or benzocaine outside the pharmacy sector
      is forbidden.

PMID- 22594254
TI  - Thiopurine S-methyltransferase phenotype-genotype correlation in children with
      acute lymphoblastic leukemia.
AB  - Thiopurine S-methyltransferase (TPMT) is an enzyme that catalyzes the S
      methylation of thiopurine drugs such as 6-mercaptopurine, 6-thioguanine, and
      azathioprine. TPMT activity exhibits an interindividual variability mainly as a
      result of genetic polymorphism. Patients with intermediate or deficient TPMT
      activity are at risk for toxicity after receiving standard doses of thiopurine
      drugs. The aim of this study was to determine the TPMT genotype and phenotype
      (activity) and investigate the correlation between TPMT genotype and enzyme
      activity in 43 Polish children receiving 6-MP during maintenance therapy in
      course of acute lymphoblastic leukemia (ALL), in 16 children with ALL at
      diagnosis and 39 healthy controls. TPMT activity was measured in RBC by HPLC
      method. Patients were genotyped for TPMT *2, *3A and *3C variant allelesusing PCR
      RFLP and allele-specific PCR methods. In the group of children with ALL during
      maintenance therapy, median TPMT activity (29.3 nmol 6-mMP g(-1) Hb h(-1)) was
      significantly higher compared to the group of children with ALL at diagnosis
      (20.6 nmol 6-mMP g(-1) Hb h(-1), p = 0.0028), as well as to the control group
      (22.8 nmol 6-mMP g(-1) Hb h(-1), p = 0.0002). Percentages of individuals
      heterozygous for TPMT variant allele in respective groups were: 9.3, 6.2 and
      15.5% (p > 0.05). In all the study groups heterozygous patients manifested a
      significantly lower TPMT activity as compared to the wild type homozygotes (16.7
      +/- 2.1 vs. 31.2 +/- 6.8 nmol 6-mMP g(-1) Hb h(-1), p = 0.002, in children during
      maintenance therapy, 11.9 +/- 2.7 vs. 24.6 +/- 9.5, p = 0.0003, in the combined
      group of children with ALL at diagnosis and controls). The results present that
      commencement of the thiopurine therapy caused an increase in the TPMT activity in
      RBCs by approximately 20%. All patients heterozygous for the TPMT variant allele
      revealed decreased TPMT activity compared to TPMT wild-type patients. Since
      decreased TPMT activity is associated with higher risk for toxicity after
      receiving standard doses of thiopurine drugs, pretreatment determination of TPMT
      status, with phenotypic or genetic assay, should be performed routinely, also in
      Poland.

PMID- 22594255
TI  - Synthesis and anti-inflammatory evaluation of new substituted 1-(3-chlorophenyl)
      3-(4-methoxyphenyl)-1H-pyrazole derivatives.
AB  - A series of heterocyclic derivatives including 1,2,4-triazole-3(4H)-one (3a,b),
      1H-pyrazol-5(4H)-one (4,5), 1H-pyrazol-4-carbonitrile (7), pyridine-3
      carbonitrile (8, 9a,b), pyrimidine-5-carbonitrile (10a,b), methylpyrimidin-2(1H)
      one or thione (11a,b), pyrimidine-5-carboxylate (12a,b), quinazolin-5(6H)-one
      (13a,b) and indeno [1,2-d] pyrimidin-5-one (14a,b) moieties conjugated with 1,3
      disubstituted pyrazole moiety were synthesized on reaction with semicarbazide,
      thiosemicarbazide, 3-amino-5-oxo-2-pyrazoline, cyanoacetohydrazide, 2-acetyl
      thiophene, p-chloroacetophenone, urea, thiourea and 1,3-dicarbonyl compounds,
      respectively, by using 1-(3-chlorophenyl)-3-(4-methoxyphenyl)-1H-pyrazole-4
      carboxaldehyde (2) as starting material. The structures of all the newly
      synthesized products have been established on the basis of analytical and
      spectral data. The anti-inflammatory screening showed that most of the obtained
      compounds were found to have significant anti-inflammatory activities with
      prostaglandin inhibition at a dose level of 2.5 and 5 mg/kg comparable to
      celecoxib as a reference control. The ulcer indices of all compounds are mainly
      in the safe level (UI = 2.10-4.27) except for compounds 9a and 14a, which were
      highly ulcerogenic.

PMID- 22594256
TI  - Microwave assisted synthesis and determination of in-vitro antimicrobial efficacy
      of well characterized s-triazinyl piperazines and piperidines.
AB  - An easy and convenient microwave-assisted synthesis of a library of s-triazinyl
      piperazines and piperidines, which, in addition to 4-aminobenzonitrile contain 8
      hydroxyquinoline is described. The newly synthesized analogues were then
      subjected to determine their efficacy against some human pathogenic bacterial and
      fungal strains as 3 Gram negative bacteria (K. pneumoniae, S. typhi, P.
      vulgaris), 1 Gram positive bacteria (B. cereus) and 2 fungal species (A.
      clavatus, A. fumigatus) with an intent to develop novel class of antimicrobial
      agents. Microwave irradiation method was adopted for the final nucleophilic
      reactions, facilitates the condensation of piperazine and piperidine substituents
      to the s-triazine core. The results of bioassay showed that some of the newly
      synthesized s-triazines emerged as lead molecules with excellent MIC (mg/mL)
      values against the full array of bacterial and fungal pathogens comparable to the
      commercial antibiotics. The structure of final scaffolds has been affirmed on the
      basis of IR, 1H NMR, 13C NMR, 19F NMR and elemental analyses.

PMID- 22594257
TI  - Synthesis and characterization of (Z)-N-(1-[2-{3-[(dimethylamino)methyl)]-2
      methoxyphenyl}-5-(pyridin-4-yl)-1,3,4-oxadiazol-3(2H)-yl]ethylidene) benzenamine
      derivatives as potent antifungal agents.
AB  - In the present study, a series of (Z)-N-(1-[2-{3-[(dimethylamino)methyl)]-2
      methoxyphenyl}-5-(pyridin-4-yl)-1,3,4-oxadiazol-3(2H)-yl]ethylidene)benzenamine
      derivatives have been synthesized and characterized by IR, 1H NMR and 13C NMR
      spectra. All the synthesized compounds were evaluated for their antifungal
      activity and were compared with the standard drug, clotrimazole. The compounds
      demonstrated excellent to weak antifungal activity. Among the synthesized
      derivatives, 4f and 4h showed significant activity and 4c exhibited moderate
      activity against Candida albicans, Candida tropicalis and Aspergillus niger as
      compared with the standard antifungal agent - clotrimazole. The minimum
      inhibitory concentration of the compounds was in the range of 1.62-25 microg/mL
      against fungi. Furthermore, the substitution of chloro, nitro and methoxy groups
      at para position of benzene moiety play an important role in enhancing the
      antifungal activity of this class of compounds.

PMID- 22594258
TI  - Synthesis and antimicrobial activity of new substituted thienopyrimidines, their
      tetrazolyl and sugar derivatives.
AB  - A series of substituted 5,6,7,8-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidine-4
      one derivatives were newly synthesized starting from 5,6,7,8-tetrahydro-3H
      benzo[4,5]thieno[2,3-d]pyrimidine-4-one derivatives (1). Furthermore, their
      derived tetrazolyl as well as the N-substituted derivatives were also prepared.
      The antimicrobial activity of the prepared compounds against Escherichia coli,
      Bacillus subtilis, Staphylococcus aureus, Aspergillus niger and Candida albicans
      were evaluated. The substituted thienopyrimidine derivatives 4 and 6 as well as
      the arylidine 10 were the highly active compounds.

PMID- 22594259
TI  - Synthesis of novel N-benzyl substituted piperidine amides of 1H-indole-5
      carboxylic acid as potential inhibitors of cholinesterases.
AB  - A series of novel N-benzyl substituted amides of 1H-indole-5-carboxylic acid were
      synthesized and evaluated for their ability to inhibit acetylcholinesterase
      (AChE) and butyrylcholinesterase (BuChE). The target compounds (6b-6e) displayed
      moderate potency to inhibit BuChE. One of the compounds tested, i.e., 1
      benzylpiperidine amide of 1H-indole-5-carboxylic acid (6a) was a weak, non
      selective inhibitor for both enzymes. The highest inhibitory activity towards
      BuChE (30.06% [10 microM]) was determined for compound (6c) which is 1-(3
      chloro)benzylpiperidine amide of 1H-indole-5-carboxylic acid.

PMID- 22594260
TI  - Synergistic antibacterial activity of Salvia officinalis and Cichorium intybus
      extracts and antibiotics.
AB  - Synergistic activity of Salvia officinalis and Cichorium intybus extracts and
      commonly used antibiotics, amoxicillin and chloramphenicol, were evaluated.
      Interactions between plant extracts and antibiotics were tested by checkerboard
      method and interpreted as FIC index. Staphylococcus aureus ATCC 25923,
      Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853 and clinical
      isolates Staphylococcus aureus, Bacillus subtilis, Enterobacter cloacae,
      Klebsiella pneumoniae, Escherichia coli and Proteus mirabilis were used. Salvia
      officinalis showed better synergistic capacity than Cichorium intybus.
      Synergistic interactions were observed between amoxicillin and acetone or ethyl
      acetate extract of Salvia officinalis and between chloramphenicol and ethyl
      acetate extract of Salvia officinalis. In the presence of sub-inhibitory
      concentration (1/4 MIC to 1/32 MIC) of sage extracts, the MIC values of
      antibiotics were decreased by 2- to 10-fold. Synergism was observed against all
      test bacteria, except Escherichia coli. The combinations of acetone and ethyl
      acetate extract from Cichorium intybus and antibiotics resulted in additive and
      indifferent effects against tested bacteria.

PMID- 22594261
TI  - Bronchorelaxant, mast cell stabilizing, anti-inflammatory and antioxidant
      activity of Randia dumetorum (Retz.) Lamk. extracts.
AB  - Randia dumetorum (RD) fruits in different form have been ethnopharmacologically
      reported to possess antiasthmatic property. Therefore, present study was
      undertaken to evaluate two different extracts of RD i.e., ethyl acetate (RD-EA)
      and methanol (RD-ME) for bronchorelaxant, anti-inflammatory, mast cell
      stabilizing and antioxidant effect along with safety margin, according to OECD
      guidelines for toxicity. RD-ME and RD-EA (1 mg/mL) exhibited 68.75 and 57.39%
      inhibition of contraction against acetylcholine, while against histamine induced
      contraction, inhibition observed was 100 and 78.13%, respectively. Moreover,
      extracts attenuated the experimentally induced inflammation at 200 mg/kg with %
      inhibition of 41.62 by RD-ME and 30.36 by RD-EA in carrageenan model, while in
      egg albumin model RD-ME and RD-EA exhibited % inhibition of 48.31 and 33.75,
      respectively. In addition, RD-ME and RD-EA at 100 microg/mL demonstrated
      significant decrease in histamine release of 08.31 and 16.71 in C-48/80 induced
      mast cell degradation. RD extracts also exhibited antioxidant activity in DPPH,
      reducing power and metal chelation method, along with safe margin for oral
      administration as observed in acute toxicity evaluation.

PMID- 22594262
TI  - Comparison of conventional and non conventional methods of extraction of
      heartwood of Pterocarpus marsupium Roxb.
AB  - The renewed interest in plant-derived drugs has led to an increased need for
      efficient extraction methods. The present investigation was an attempt to
      evaluate and compare the conventional methods of extraction with non conventional
      methods of extraction, such as ultrasonic-assisted extraction (UAE) and microwave
      assisted extraction (MAE) methods. Pterocarpus marsupium Roxb. has been reported
      to contain bioactive phytochemicals, e.g., pterostilbene (3',5'-dimethoxy-4
      stilbenol). The results showed that among the conventional extraction methods,
      percolation gave the highest yield. The non conventional methods were optimized.
      The extraction yield was the highest in case of MAE. The phytochemical screening
      of the extracts indicated similar groups of compounds in all the extracts. The
      thin layer chromatography showed the presence of pterostilbene in the extracts
      obtained by using percolation, MAE and UAE. In these extracts the quantification
      of pterostilbene was conducted by high performance liquid chromatography and the
      method was validated. The MAE method extracted significantly higher amount of
      pterostilbene.

PMID- 22594263
TI  - Rumex L. species induce apoptosis in 1301, EOL-1 and H-9 cell lines.
AB  - The Rumex L. (dock) species for many centuries have been used in medical
      treatment, through their adstringent, spasmolitic or cholagogic action. In the
      present study, the in vitro screening of cytotoxic activities of ethanol extract
      from roots, leaves and fruits of six Rumex species: R. acetosa L., R. acetosella
      L., R. confertus Willd., R. crispus L., R. hydrolapathum Huds. and R.
      obtusifolius L. were performed. We found remarkable cytotoxic activities on
      leukemic 1301 and EOL-1 cell lines and T cell line at concentration dependent
      manners. Cytotoxic activity was determined in two ways: trypan blue test and
      annexin-V FITC and propidium iodide assay. Received IC50 values of investigated
      extracts on 1301, EOL-1 and H-9 cell lines ranged from 0.22, 0.17 and 0.04 to
      2.56, 1.91 and 1.83 mg/mL, respectively. Analysis of morphological changes
      demonstrated that the extract exerted cell-death via apoptosis. The overall
      activities of Rumex species support the traditional use of the extract from the
      fruits of R. confertus, R. crispus, R. hydrolapathum and R. obtusifolius in the
      treatment of cancer.

PMID- 22594264
TI  - Influence of different extraction procedures on the antiradical activity and
      phenolic profile of Rosa rugosa petals.
AB  - The present study was designed to develop conditions for the optimal extraction
      of antiradical ingredients of rugosa rose petals. The effect of temperature (22
      140 degrees C), solvent and extraction type on the phenolics extraction and
      antiradical activity was studied. In order to obtain extracts from rugosa rose
      petals with the highest activity and phenolic content, the use of mixture of
      polar organic solvents (acetone, in particular) with water is recommended.

PMID- 22594265
TI  - Preparation and in vitro evaluation of chitosan microgranules with clotrimazole.
AB  - Mucoadhesive polymers have gained much attention due to the possibility to
      overcome physiological barriers in long-term drug delivery. Chitosan is a
      biocompatible and non-toxic chitin derivative, which due to its mucoadhesive
      properties enables to obtain prolonged drug delivery. The aim of this study was
      to formulate and in vitro evaluate chitosan microgranules with clotrimazole.
      Microgranules were prepared by the wet-granulation method using pentabasic
      tripolyphosphate (TPP) as an ion cross-linker. It was shown that crosslinked
      chitosan significantly prolonged the release of clotrimazole. Microgranules in
      formulation F4 (with chitosan:clotrimazole:TPP ratio 5:1:1) not only maintained
      regular surface morphology, but also ensured prolonged release of clotrimazole
      over the period of 6 h. The obtained results indicate that chitosan is a suitable
      polymer for developing a sustained-release dosage form of clotrimazole for local
      delivery.

PMID- 22594266
TI  - Preparation and characterization of floating drug delivery system of
      azithromycin.
AB  - The objective of present study was to develop a stomach drug delivery system of
      azithromycin (AZH) as a model drug for eradication of Helicobacter pyloni (H.
      pylori). Floating microspheres of AZH were prepared by the solvent evaporation
      method. The prepared microspheres were subjected to evaluation for particle size,
      incorporation efficiency, in vitro buoyancy and in vitro drug release
      characteristics. The formulations were prepared at a variable stirring rate (300
      to 500 rpm) and temperature (30-50 degrees C). Surface morphology characteristics
      were studied using scanning electron microscopy (SEM). The mean particle size of
      the microspheres significantly increased with increasing polymer concentration
      and was in the range 252.26 +/- 6.50 to 380.91 +/- 4.59 microm. Angle of repose
      was between 26.42 to 35.83 degrees. Tapped density ranged between 0.493 to 0.612
      g/cm3. The compressibility index of all formulations was found to be in the range
      of 12.41 to 17.16%, which was < 20 indicating good flow characteristics. The
      encapsulation efficiency of the prepared microspheres was in the range of 27.8 +/
      4.30 to 66.23 +/- 2.08%. The physical state of the drug, before and after
      formulation was determined by differential scanning calorimetry (DSC). Percentage
      buoyancy of the microspheres was in the range 45.52 +/- 0.69 to 68.71 +/- 0.61%
      for 8 h. In vitro drug release studies were performed in simulated
      gastrointestinal fluid (SGF), pH 2.0 as dissolution medium (900 mL) for 8 h.
      Effects of stirring rate during preparation, polymer concentration and
      temperature on the size of microspheres and drug release were also observed. The
      results of the present studies indicated that the floating microspheres of AZH
      were formulated to provide site specific delivery of drug with a view to provide
      an effective and safe therapy for eradication of H. pylori with a reduced dose
      and reduced duration of therapy.

PMID- 22594267
TI  - Trial analytics--a tool for clinical trial management.
AB  - Prolonged timelines and large expenses associated with clinical trials have
      prompted a new focus on improving the operational efficiency of clinical trials
      by use of Clinical Trial Management Systems (CTMS) in order to improve managerial
      control in trial conduct. However, current CTMS systems are not able to meet the
      expectations due to various shortcomings like inability of timely reporting and
      trend visualization within/beyond an organization. To overcome these shortcomings
      of CTMS, clinical researchers can apply a business intelligence (BI) framework to
      create Clinical Research Intelligence (CLRI) for optimization of data collection
      and analytics. This paper proposes the usage of an innovative and collaborative
      visualization tool (CTA) as CTMS "add-on" to help overwhelm these deficiencies of
      traditional CTMS, with suitable examples.

PMID- 22594268
TI  - Cheminformatics based 3D-QSAR study on a series of 1,2-naphthoquinone derivatives
      as PTP 1B inhibitors.
AB  - Self-organizing molecular field analysis (SOMFA), a simple three-dimensional
      quantitative structure activity relationship (3D-QSAR) based cheminformatics
      method was used in present case to study the correlation between the molecular
      properties and the PTP 1B inhibitory activities of a series of 1,2-naphthoquinone
      that acts as selective PTP 1B inhibitors. The statistical results, cross
      validated r2(cv) and non cross-validated r2, F-test value showed a satisfied
      predictive ability (r2(pred)). The spatial arrangement of the shape and
      electrostatic potential could be used as a guide for further development of
      selective and more potent PTP 1B inhibitors.

PMID- 22594269
TI  - Antihepatotoxic activity of aqueous extracts of callus culture of Tephrosia
      purpurea (L) pers.

PMID- 22594270
TI  - Effects of sodium fluoride on DNA, RNA and protein contents in liver of mice and
      its amelioration by Camellia sinensis.

PMID- 22594271
TI  - Quercetin ameliorates bisphenol A-induced toxicity in mice.

PMID- 22594272
TI  - In vitro activity of the azole compounds against clinical fungal strains.

PMID- 22594273
TI  - [Diffusion factor calculation for TIP4P model of water].
AB  - A molecular dynamics study has been undertaken for a model of liquid TIP4P water.
      Thermal dependencies of water density and radial distribution functions were
      calculated for model verification. Three methods have been used for calculation
      of diffusion factor thermal dependencies. Their sensitivity to molecular system
      size and length of used trajectory has been analyzed. It has been shown that
      Green-Kubo formula-based approach which associates diffusion factor with speed
      autocorrelation function integral is preferred in case of short MD simulations.
      The second approach based on Einstein equation which associates mean square
      displacement of molecule with time is preferred in case of long simulations. It
      has been also demonstrated that it is possible to modify the second approach to
      make it more stable and reliable. This modification is to use a slope of the
      graph of the mean square displacement on time as the estimation of the diffusion
      factor instead of the ratio of molecule mean square displacement and time.

PMID- 22594274
TI  - [Verification of the PREFAB alignment database].
AB  - The verification of the PREFAB database containing golden standard protein
      alignments was performed. It has revealed a significant number of differences
      between the sequences from PREFAB and PDB databases. It was shown that compared
      to the sequences given in the PDB database 575 alignments refered to a sequence
      with a gap; such alignments were excluded. Furthermore, compared to the PDB
      sequences a single substitute or the insertions were found for 440 aminoacid
      sequences from PREFAB database; these sequences were edited. SCOP domain analysis
      has shown that only 502 alignments in the resulting set contain the sequences
      from the same family. Finally, eliminating duplicates, we have created a new
      golden standard alignment database PREFAB-P based on PREFAB; the PREFAB-P
      database contains 581 alignments.

PMID- 22594275
TI  - [Correlations between clusters of protein-DNA binding sites and the binding
      experimental data allow to predict a structure of regulatory modules].
AB  - Here we analyzed an option to predict the structure of cis-regulatory modules
      that consist of binding sites of different proteins (heterogeneous cis-regulatory
      modules) using mutual positional correlations between protein-DNA binding
      experimental data and computationally identified clusters of binding sites for
      each of the proteins.

PMID- 22594276
TI  - [Analysis of protein-on-DNA binding profiles, detected with chIP-seq method,
      reveals possible interaction of specific transcription factors with RNA
      polymerase II in the process of transcription elongation].
AB  - It is thought that in the course of mRNA transcription almost all transcription
      factors stay on a promoter while RNA polymerase II "clears" the promoter and
      "proceeds" to elongation. However, analysis of some specific transcription
      factors and RNA polymerase II binding profiles on DNA, detected with ChIP-seq
      method, revealed the possibility of interaction between transcription factors and
      RNA polymerase II in the process of transcription elongation.

PMID- 22594277
TI  - [Calculation of spectral shifts of the mutants of bacteriorhodopsin by QM/MM
      methods].
AB  - In the present work spectral shifts of adsorption maxima for the number of
      mutants of bacteriorhodopsin have been calculated using QM/MM hybrid methodology.
      Along with this calculation an analysis of possible mechanisms of spectral
      modulation has been performed. Also we have carried out a comparative analysis of
      modern quantum chemical methods in respect of the level of optical spectra
      predictability they allow. We have shown that modern hybrid quantum chemical
      methods reach an acceptable level of preciseness when applied in the calculation
      of spectral shifts even if the absolute values of adsorption maxima predicted by
      these methods are underestimated. The number of rules has been found linking the
      value of spectral shift with the structural rearrangement in the apoprotein. The
      methods we were using as well as those rules we have found out both may be useful
      for development of nanoelectronical devices based on mutant species of
      bacteriorhodopsin (memory elements, optical triggers etc.).

PMID- 22594278
TI  - [Inhibition of herpes simplex virus helicase UL9 by netropsin derivatives and
      antiviral activities of bis-netropsins].
AB  - Data obtained show that antiviral activities of bis-linked netropsin derivatives
      are targeted by specific complexes formed by helicase UL9 of herpes simplex virus
      type 1 with viral DNA replication origins, represented by two OriS sites and one
      OriL site. According to the results of footprinting studies bis-netropsins get
      bound selectively to an A+T-cluster which separates interaction sites I and II
      for helicase UL9 in OriS. Upon binding to DNA bis-netropsins stabilize a
      structure of the A+T-cluster and inhibit thermal fluctuation-induced opening of
      AT- base pairs which is needed for local unwinding of DNA by helicase UL9.
      Kinetics of ATP-dependent DNA unwinding in the presence and absence of Pt-bis
      netropsin are studied by measuring the efficiency of Forster resonance energy
      transfer (FRET) between the fluorescent probes attached covalently to 3?- and 5?
      ends of the oligonucleotides in the minimal OriS duplex. Pt-bis-netropsin and
      related molecules inhibit unwinding of OriS duplex by helicase UL9. Pt-bis
      netropsin is also able to reduce the rate of unwinding of the AT- rich hairpin
      formed by the upper strand in the minimal OriS duplex. The antiviral activities
      and toxicity of bis-linked netropsin derivatives are studied in cell cultured
      experiments and experiments with animals infected by herpes virus.

PMID- 22594279
TI  - [On the efficiency of energy migration from chlorosoma to the main
      bacteriochlorophyll in green bacteria].
AB  - It is shown that the results provided in a variety of publications, which deal
      with structural characterization of green bacteria chlorosoma, are in explicit
      contradiction with kinetic and energy characteristics of microorganisms studied.
      The data on chlorosoma structure and composition represent no explanation as to
      how the additional quantity of electronic excitations generated by light in its
      dominating pigment C750 feeds the main photosystem.. In order to reveal the
      contradictions, the structural and spectral data on chlorosoma are analyzed in
      cooperation with the theory of inductive resonance developed by T. Ferster.

PMID- 22594280
TI  - [The sources of inorganic sulfur in the process of cluster protein Fnr[4Fe-4S]2+
      reconstruction in Escherichia coli cells cultivated with NO-donating agents].
AB  - Dinitrosyl iron complexes (DNICs) with thiol ligands--binuclear and mononuclear-
      inhibited aidB gene expression in E. coli cells. This process is due to the
      nitrosylation of the active center in iron-sulfur protein Fnr [4Fe-4S]2+ by low
      molecular DNICs. The next step is transformation of the above DNICs into the
      DNICs with the thiol groups in the apo-form of Fnr protein. These nitrosylated
      proteins are characterized by the EPR signal with g perpendicular = 2.04 and g
      parallel 1 = 2,014. An addition of sulfur containing L-Cys or N-A-L-Cys as well
      as Na2S to the cells lead to the increasing in the aidB gene expression
      simultaneously with an appearance of the EPR signal with g perpendicular = 2.04
      and g parallel = 2.02 as the characteristics of the DNICs with persulfide (R-S-S
      ) ligands. We suppose that the recovery of the aidB gene activity was due to the
      accumulation of inorganic sulfur in the cells and reconstruction of the active
      center in Fnr[4Fe-4S]2+. It appears that the above process is the function of L
      cysteine-desulfurase protein which repaired the active center of Fnr[4Fe-4S]2+
      protein using the sulfur from L-Cys or N-A-L-Cys after its deacetylation. On the
      other side the ions of inorganic sulfur being reacted with SH-groups led to the
      transformation of DNIC with thiol ligands into the persulfides. Na2S was the most
      potent activator of the aidB gene expression in our experiments.

PMID- 22594281
TI  - [Extracellular acidification leads to reactive oxygene species formation in rat
      brain synaptosomes].
AB  - Formation of reactive oxygen species in rat brain synaptosomes was studied using
      DCFDA fluorescent dye at lowered extracellular pH. It has been shown that
      decrease in pH value from 7.4 to 7.0 and up to 6.0 leads to increase of
      fluorescence that is indicative of oxidative stress. The effect is observed
      regardless of whether Ca ions are present in incubation medium or no.
      Acidification of the incubation medium induces quenching of fluorescence of
      previously oxidized form of the dye in experiments without synaptosomes This
      evidences that increase of dye fluorescence is really associated with reactive
      oxygen species accumulation. Thus, it has been demonstrated that pH declined up
      to 7.0 in the incubation medium is sufficient to induce the formation of reactive
      oxygen species in synaptosomes.

PMID- 22594282
TI  - [Antioxidant properties of the pollen exine polymer matrix].
AB  - The antioxidant properties of exine polymer matrix which forms the outer layer of
      pollen grain wall were studied. The main component of this matrix is
      sporopollenin - a unique biopolymer resistant to mechanical and chemical damage.
      The samples of isolated exine, purified from soluble compounds, were studied with
      EPR using stable nitroxyl radical TEMPO and DMPO spin trap. At the same time, we
      analyzed changes in fluorescence of DCFH which detected ROS in the solution. It
      has been established that exine effectively reduces TEMPO radical and eliminates
      hydroxyl radical. Also, the fluorometric analysis demonstrated that the exine
      eliminated H2O2, and this ability significantly decreased after treatment of
      exine with feruloyl esterase or mild alkaline hydrolysis (1M NaOH), i.e. after
      hydrolysis of hydroxycinnamic acid esters. After harsh hydrolysis (4M NaOH, 170
      degrees C) of ethers bonds a large amount of hydroxycinnamic acids has been
      released, and exines have lost their antioxidant capacity almost completely. The
      obtained results point to the ability of extracellular polymer matrix of the
      exine to eliminate free radicals and H2O2 during crucial periods of male
      gametophyte development. The participation of ferulic acid and, possibly, of
      other hydroxycinnamic acids of sporopollenin in these processes has been
      demonstrated.

PMID- 22594283
TI  - [Study of interaction of polystirolsulphonate with polymerization degree of 8 and
      polyallylamin with bilayer lipids membranes].
AB  - Interaction of polystirolsulphonate with polymerization degree of 8 (PSS-8) and
      polyallylamin PAA (molecular mass 60 kilodaltons) with viruses from bloodline of
      paramixo- and orthomixoviruses by the example of measles virus, parotitis and flu
      leads to the decreasing of infective activity. The possible mechanism of viral
      inhibitive action of these chemical compounds is damaging of interfacial
      antigenic proteins of paramixo- and orthomixoviruses. In this study it was
      detected the change of surface tension of bilayer lipid membrane in the presence
      of PSS-8 and PAA. The change of surface tension leads to disorder in viral
      proteins adsorption in bilayer lipid membrane. This process could lead to
      disorder of juncture and self-assembly of virions.

PMID- 22594284
TI  - [Simulation of the uncoupling activity of fatty acids with the participation of
      ADP/ATP and aspartate/glutamate antiporters in liver mitochondria].
AB  - It has been found that the protonophoric specific uncoupling activity of palmitic
      acid in rat liver mitochondria does not change as its concentration increases
      from 5 to 40 microM. Under these conditions, the component of the specific
      uncoupling activity, which describes the participation in uncoupling of the
      ADP/ATP antiporter (sensitive to carboxyatractylate), increases, and the
      component of specific uncoupling activity, which characterizes the participation
      in the uncoupling of the aspartate/glutamate antiporter (sensitive to glutamate),
      decreases by the same value. A kinetic model of the fatty acid-induced uncoupling
      activity with the participation of ADP/ATP and aspartate/glutamate antiporters
      has been developed. According to the model, these carriers can exist in two
      forms: an active, i.e., participating in the uncoupling, and an inactive. The
      interaction of a fatty acid with the regulator site of the ADP/ATP antiporter
      translates it from the inactive to the active form, while the interaction of a
      fatty acid with the regulator site of the aspartate/glutamate antiporter, on the
      contrary, translates it from the active form to inactive. The velocity of
      transport of a fatty acid anion by the antiporter from the internal monolayer of
      the internal membrane to the external monolayer is proportional to the product of
      the concentration of the fatty acid and the active form of this carrier. A good
      conformity of the model to experimentally obtained data is shown provided that
      (a) ADP/ATP and aspartate/glutamate antiporters, being completely in an active
      state, transfer fatty acid anions with the same velocity; (b) the equilibrium
      dissociation constants of a complex of the carrier with the fatty acid in these
      antiporters are equal.

PMID- 22594286
TI  - [Phosphorescence quenching as an approach for estimating localization of triplet
      label in cotton fibers].
AB  - The method based on the qualitative investigation of chromophore fluorescence
      (phosphorescence) quenching for instance, by stable nitroxide radical was first
      used to measure the depth of immersion of triplet label in cotton fiber as a
      molecular object. The concept of dynamic quenching of fluorescence in solutions
      and the empirical dependence of the parameters of static quenching between
      centers with fixed distances were used. The erythrosine triplet labels were
      incorporated in cotton fibers with subsequent measurement of the efficiency of
      label phosphorescence quenching and determination of temperature dependence of
      phosphorescence duration. Using above mentioned approach it became possible for
      the first time to estimate the depth of immersion of chromophore fragment of the
      labels (7.4-7.8 A) and study their molecular dynamics in the millisecond range of
      correlation times. Subtle differences in microstructure and molecular dynamics of
      the investigated samples were revealed. The proposed approach can be used for
      investigation of widespread biological and nonbiological objects.

PMID- 22594285
TI  - [The role of tetrapyrrol photosensitizers in photoinduced variation of free
      radical characteristics of rat blood in endotoxic shock].
AB  - The main goal of the present study was to evaluate the comparative effectiveness
      of tetrapyrrol photosensitizers (protoporphyrine IX and chlorine e6) in red
      (632.8 nm) and green (532.5) spectrum bands on rat blood free radical status,
      using the experimental model of endotoxic shock. Endotoxic shock was produced by
      intraperitoneal injection of lipopolysaccharide B. Irradiation effectiveness was
      estimated by leukocyte activation (measured with luminol-dependent
      chemiluminescence), superoxide dismutase activity of blood plasma (nitro blue
      tetrasolium assay) and lipid peroxidation (assay with cis-parinaric acid). It was
      found that laser irradiation has multidirectional effects on leukocyte
      activation, membrane lipid peroxidation and plasma SOD activity and all these
      effects were more pronounced in the case of endotoxic shock. Protoporphyrin was
      more effective in leukocyte activation and chlorine e6 demonstrated maximal
      effects on blood SOD activity.

PMID- 22594287
TI  - [Changes in the composition of cardiac muscle myosin light chains during cardiac
      diseases].
AB  - In this paper our data of the study on composition of human cardiac myosin light
      chains in norm and its changes at different stages of dilated cardiomyopathy and
      heart valvular diseases are presented. Functional role and diagnostic value of
      these changes are discussed.

PMID- 22594288
TI  - [Mechanisms of human plasma proteins adsorption on the surface of perfluorocarbon
      emulsion stabilized with proxanol 268].
AB  - It has been shown that sorption of most proteins with the molecular weight lower
      than 200 kDa from human blood plasma on the surface of perfluorocarbon emulsion,
      stabilized with proxanol 268, is mainly based on hydrophobic interaction, whereas
      sorption of immunoglobulin G is mainly the result of electrostatic interaction.
      The removal of lipidic components from plasma leads to the increase of a total
      amount of adsorbed proteins by 35%. Particularly, when lipidic components are
      removed, sorption of apolipoprotein AI and immunoglobulin G is considerably
      bettered as well as sorption of other proteins with the molecular weight of about
      50 and 60 kDa occurs. It has been out that apolipoprotein AI in the adsorbed
      condition loses its capability of tryptophan fluorescence, which might be
      probably determined by the quenching influence of the perfluorocarbon core of
      nanoparticle. We think that the findings obtained also indicates considerable
      conformational rearrangements of this protein during adsorption. It was shown,
      that the fluorescence of proteins with sorption on nanoparticles in emulsion
      based on the hydrophobic interaction, is completely or partially quenched.

PMID- 22594289
TI  - [Blood plasma protein adsorption capacity of perfluorocarbon emulsion stabilized
      by proxanol 268 (in vitro and in vivo studies)].
AB  - The adsorption abilities of the perfluorocarbon emulsion stabilized by Proxanol
      268 were investigated in vitro and in vivo. In vitro, the saturation point for
      the blood plasma proteins was nearly reached after five minutes of incubation of
      the emulsion with human/rabbit blood plasma and was stable for all incubation
      periods studied. The decrease in volume ratio (emulsion/plasma) was accompanied
      by the increase in the adsorptive capacity of the emulsion with maximal values at
      1/10 (3.2 and 1.5 mg of proteins per 1 ml of the emulsion, for human and rabbit
      blood plasma, respectively) that was unchanged at lower ratios. In vivo, in
      rabbits, intravenously injected with the emulsion, the proteins with molecular
      masses of 12, 25, 32, 44, 55, 70, and 200 kDa were adsorbed by the emulsion (as
      in vitro) if it was used 6 hours or less before testing. More delayed testing (6
      h) revealed elimination of proteins with molecular masses of 25 and 44 kDa and an
      additional pool of adsorpted new ones of 27, 50, and 150 kDa. Specific adsorptive
      capacity of the emulsion enhanced gradually after emulsion injection and reached
      its maximum (3.5-5 mg of proteins per 1 ml of the emulsion) after 24 hours.

PMID- 22594291
TI  - [Study of dinitrosyl-iron complexes pharmacokinetics and accumulation in depot in
      rat organs].
AB  - Protein-bound dinitrosyl-iron complexes (DNIC) in rat whole blood and organs were
      studied after intravenous injection of this substance with glutathione ligand
      (DNIC-GH). The effect of DNIC-GH injection on NO level (including NO
      physiological forms) in hydrophobic areas of rat tissues was also studied in
      normal physiological blood circulation condition. It has been shown, that after
      DNIC-GH injection the concentration of protein-bound DNICs in rat whole blood and
      organs rapidly reached maximum values, and then gradually decreased, that pointed
      to decomposition of DNIC molecules, coupled with NO release. At the beginning of
      the experiment the rates of DNIC decay in rat heart and lung were substantially
      higher, as compared with those in liver and kidney. By spin trappping it has been
      demonstrated that DNIC-GH, as a source of NO physiological forms (including S
      nitrosothiols), in normal physiological blood circulation influence heart more
      selectively, as compared with the other organs.

PMID- 22594290
TI  - [Modification of the nitric oxide concentration regulates the development of the
      apoptosis in the eye retina].
AB  - Using model elaborated it was shown that the retinal ischemia initiated the
      development of the apoptosis in the inner layers of the retina. Administration of
      NOS inhibitor prevented the development of the apoptosis in the retina. To
      ascertain if nitric oxide could induce the retinal apoptosis by itself the
      nontoxic donor of nitric oxide (dinitrosyl iron complex) was injected
      intravitreally. Administration of DNIC in low concentrations induced the
      development of the apoptosis in the same retinal layers as in ischemia. The
      injection of dinitrosyl iron complex at the higher concentration resulted in the
      decrease of the apoptosis level. Administration of dinitrosyl iron complex with
      excess of glutathione didn't lead to the development of the retinal apoptosis.
      The obtained data demonstrates the neurotoxic properties of the excess of nitric
      oxide in the retina.

PMID- 22594292
TI  - [Two types of magnetic biological effects: individual and batch effects].
AB  - Frequency distributions of the magnetic effects values have been calculated based
      on the results of about 120 thousand single trials during psychophysical testing
      of 40 people under normal conditions and exposure to the hundredfold weakened
      geomagnetic field. Two types of such distributions were shown to be attributed to
      a) the individual reactions to the change of a magnetic field and b) the batch
      magnetic effect on the set of the individual reactions. The methodological
      consequences significant for detecting magnetic biological phenomena and studying
      their nature are discussed.

PMID- 22594293
TI  - [The effect of combined magnetic fields, adjusted to ion-cyclotron resonance for
      Ca ions, on intensity of division in planaria].
AB  - The combination of a constant (42 mkT1) and parallel to it a changing magnetic
      field on a frequency of 32 Hz (it corresponds to cyclotron frequency for Ca2+
      ions) is shown to have a changing magnetic field amplitude-dependent effect on
      intensity of division in planaria. A stimulating effect has been observed at the
      magnitude of a changing component equal to 100 nT, but the amount of division
      significantly decreased at 250 nT and no impact of the magnetic field was
      registered at 500 nT1.

PMID- 22594294
TI  - [Computer modeling of ventricular fibrillation].
AB  - Electrical activity of a heart in ventricular fibrillation was modeled as a sum
      of independent pulse streams with various amplitude-frequency and phase
      characteristics. Results of computer experiments were compared with those of real
      physiological experiments on rabbits. Identification of the model was carried out
      by means of the least-squares procedure. The offered technique allows a computer
      model investigation of internal structure of irregularities of ventricular
      fibrillation.

PMID- 22594295
TI  - [Competition and adaptation in community of migrating fish populations].
AB  - Within a discrete scheme the process of population migration is set by some non
      negative Markov matrix. When studying an appropriate class of competition models,
      nonlinear methods of the convex analysis (the theory of monotonous operators)
      proved to be highly effective. For special matrixes (cyclic and perron ones)
      conditions of steady coexistence and competitor replacement in community have
      been found. Modeling mechanisms of adaptation of a route of migration for
      separate population and also for the family of populations from one vertical
      trophic chain have been provided. The major characteristic of a route of
      migration turned out to be the relative time of population dwelling in one or
      another area. Specific (perron) vectors of migration matrixes correspond to these
      populations. It is revealed that in the course of coadaptation perron vectors of
      predator and victim migration matrixes practically coincide.

PMID- 22594296
TI  - [DNA damage by active oxygen species in cryopreservation and the antioxydative
      properties of cryoprotectants].
AB  - Several disorders in the DNA structure in the cells of vertebrate and
      invertebrate animals, plant and algae are reviewed. Some causes of the DNA
      disorders, the reactive oxygen species, especially, are discussed. Some data are
      shown, that the common used cryoprotectants such as dimethylsulfoxide, glycerol,
      methanol, sucrose and albumin, are OH* scavengers. Some seldom used
      cryoprotectors, which scavenges several forms of active oxygen, are described. It
      is supposed that the antioxidant properties of the cryoprotectors are essential
      for their mechanism of action.

PMID- 22594297
TI  - [Development of biological models of hysteresis live systems of the osseous
      tissue and periosteum].
AB  - Biological models of osseous tissue and periosteum have been developed.
      Biocompatible materials from titaniumnickel as an organic part of implant -
      tissue composites have been already functioning for five years, replacing injured
      osteal fragments. The defects of skeletal kinematic sections of the mandible of
      experiment animals were replaced by biomechanical models of implant - tissue
      composites of the osseous tissue and periosteum. The composites were formed by
      joining the models of extracellular matrices of osseous tissue and periosteum and
      natural tissues. The validity of methodological propositions and optimum
      technological solutions have been proved by the absence of life-time signs of
      biochemical, biomechanical, hysteresis, and thermodynamic incompatibility on
      tissue and skeletal levels.

PMID- 22594298
TI  - [About a new biophysical approach for total vaccination of humans and animals].
AB  - The new method of total nonspecific vaccination of humans and animals is
      presented based on the experience of practical use of a powerful light pulse for
      air disinfection in laboratory facilities.

PMID- 22594299
TI  - Atmospheric pressure photoionization mass spectrometry of fullerenes.
AB  - Atmospheric pressure photoionization (APPI) was evaluated for the analysis of
      fullerenes. An important response improvement was found when using toluene
      mediated APPI in negative mode if compared with other atmospheric pressure
      ionization (API) sources (electrospray and atmospheric pressure chemical
      ionization). Fullerene APPI negative mass spectra were dominated by the isotopic
      cluster of the molecular ion, although isotopic patterns for M+1, M+2, and M+3
      ions showed higher than expected relative abundances. These discrepancies are
      explained by the presence of two isobaric ions, one due to (13)C and the other
      due to the addition of hydrogen to a double bond of the fullerene structure.
      Triple quadrupole tandem mass spectrometry, ultrahigh resolution mass
      spectrometry, and accurate mass measurements were used to confirm these
      assignments. Additionally, cluster ions M+16 and M+32 were characterized
      following the same strategy. Ions due to the addition of oxygen and alkyl
      additions were attributed to the presence of methanol in the mobile phase. For
      the fast chromatographic separation of fullerenes (less than 3.5 min), a sub-2
      MUm C18 column and isocratic elution (toluene/methanol, 45:55 v/v) was used.
      Highly selective-selected ion monitoring (H-SIM) mode (mass resolving power,
      >12,500 fwhm) was proposed monitoring the two most intense isotope ions in the
      [M](-*) cluster. Method limits of quantitation down to 10 pg L(-1) for C(60) and
      C(70) fullerenes and between 0.75 and 5.0 ng L(-1) for larger fullerenes were
      obtained. Finally, the ultrahigh performance liquid chromatography (UHPLC)-APPI
      MS method was used to analyze fullerenes in river and pond water samples.

PMID- 22594300
TI  - Influence of embedded nanocontainers on the efficiency of active anticorrosive
      coatings for aluminum alloys part I: influence of nanocontainer concentration.
AB  - This work presents an effective anticorrosive coating for the industrially
      important aluminum alloy, AA2024-T3. The protective coating was designed by
      dispersing mesoporous silica nanocontainers, loaded with the nontoxic corrosion
      inhibitor, 2-mercaptobenzothiazole, in a hybrid sol-gel (SiOx/ZrOx) layer. The
      concentration of the embedded nanocontainers was varied (0.04-1.7 wt %) to
      ascertain the optimum conditions for anticorrosion performance. Attaining high
      efficiency was found to be a compromise between delivering sufficient corrosion
      inhibitor and preserving the coating barrier properties. The impact of
      nanocontainer concentration on the thickness and adhesion of freshly cured
      coatings was also investigated. The barrier properties of the intact coatings
      were assessed by electrochemical impedance spectroscopy. The active corrosion
      inhibition was evaluated during a simulated corrosion process by the scanning
      vibrating electrode technique. This study has led to a better understanding of
      the factors influencing the anticorrosion performance and properties of active
      anticorrosive coatings with embedded nanocontainers. 

PMID- 22594301
TI  - The influence of gender on the relationship between dental anxiety and oral
      health-related emotional well-being.
AB  - BACKGROUND AND AIM.  Children's dental fear and/or anxiety (DFA) has been
      associated with declines in oral health and quality of life. The influence of
      gender on the relationship between DFA and oral health-related well-being in
      children is analysed. DESIGN.  The decayed, missing and filled permanent teeth
      (DMFT) index was obtained from 161 school-aged children (7-14 years old). Data
      from children's self-assessed oral health, oral health-related emotional well
      being and dental anxiety were collected using questionnaires. RESULTS.  Low
      scores of emotional well-being were associated with negative self-assessment of
      oral health and high levels of dental anxiety. Females reported decreased oral
      health-related emotional well-being compared with males. The analysis of possible
      moderating effects confirmed that gender influenced the relationship between oral
      health and DFA. The DMFT index was not associated with self-assessed oral health
      status, emotional well-being or DFA. CONCLUSION.  For girls, high levels of DFA
      were associated with low levels of oral health-related emotional well-being. In
      contrast, dental fear and/or anxiety did not influence oral health-related
      emotional well-being in boys.

PMID- 22594303
TI  - Reaction of singlet oxygen with tryptophan in proteins: a pronounced effect of
      the local environment on the reaction rate.
AB  - Singlet molecular oxygen, O(2)(a(1)Delta(g)), can influence many processes
      pertinent to the function of biological systems, including events that result in
      cell death. Many of these processes involve a reaction between singlet oxygen and
      a given amino acid in a protein. As a result, the behavior of that protein can
      change, either because of a structural alteration and/or a direct modification of
      an active site. Surprisingly, however, little is known about rate constants for
      reactions between singlet oxygen and amino acids when the latter are in a
      protein. In this report, we demonstrate using five separate proteins, each
      containing only a single tryptophan residue, that the rate constant for singlet
      oxygen reaction with tryptophan depends significantly on the position of this
      amino acid in the protein. Most importantly, the reaction rate constant depends
      not only on the accessibility of the tryptophan residue to oxygen, but also on
      factors that characterize the local molecular environment of the tryptophan in
      the protein. The fact that the local protein environment can either appreciably
      inhibit or accelerate the reaction of singlet oxygen with a given amino acid can
      have significant ramifications for singlet-oxygen-mediated events that perturb
      cell function.

PMID- 22594304
TI  - Solid organ donation in a child after extracorporeal membrane oxygenation,
      orthotopic heart transplantation, and ventricular assist device support.
AB  - Use of high-risk or marginal donors is the most viable short-term means to boost
      the organ supply and bridge the widening gap between the number of patients on
      the waiting list for organ transplantation and the insufficient numbers of organ
      donors. Expansion of the donor pool requires an understanding of the impact on
      survival likely to result from extending one or more high risk factors. Use of
      extended donor pool results in shorter waiting list times and limits the
      morbidity and mortality associated with long-term mechanical support needed to
      support diseased organs. In this report, we present one such example of expanding
      donor pool in which a pediatric patient donated a solid organ after two heart
      transplants and successful use of ECMO and VAD.

PMID- 22594302
TI  - Persistent dose-dependent changes in brain structure in young adults with low-to
      moderate alcohol exposure in utero.
AB  - BACKGROUND: Many children with heavy exposure to alcohol in utero display
      characteristic alterations in brain size and structure. However, the long-term
      effects of low-to-moderate alcohol exposure on these outcomes are unknown.
      METHODS: Using voxel-based morphometry and region-of-interest analyses, we
      examined the influence of lower doses of alcohol on gray and white matter
      composition in a prospectively recruited, homogeneous, well-characterized cohort
      of alcohol-exposed (n = 11, age 19.5 +/- 0.3 years) and control (n = 9, age 19.6
      +/- 0.5 years) young adults. A large proportion of the exposed individuals were
      born to mothers whose alcohol consumption during pregnancy was in the low-to
      moderate range. RESULTS: There were no differences in total brain volume or total
      gray or white matter volume between the exposed and control groups. However, gray
      matter volume was reduced in alcohol-exposed individuals in several areas
      previously reported to be affected by high levels of exposure, including the left
      cingulate gyrus, bilateral middle frontal gyri, right middle temporal gyrus, and
      right caudate nucleus. Notably, this gray matter loss was dose dependent, with
      higher exposure producing more substantial losses. CONCLUSIONS: These results
      indicate that even at low doses, alcohol exposure during pregnancy impacts brain
      development and that these effects persist into young adulthood.

PMID- 22594306
TI  - Toxic drug-induced chronic pruritus.

PMID- 22594305
TI  - Esophageal motor dysfunction plays a key role in GERD with globus sensation-
      analysis of factors promoting resistance to PPI therapy.
AB  - OBJECTIVE: Patients with gastroesophageal reflux disease (GERD) also have various
      extra-esophageal symptoms. Laryngopharyngeal reflux disease (LPRD) is a subtype
      of GERD associated with globus sensation, but proton pump inhibitor (PPI) therapy
      achieves disappointing results. This study investigated esophageal motility in
      GERD patients with globus sensation who were resistant to PPI therapy. DESIGN:
      The subjects were 350 patients with globus sensation. All patients underwent both
      laryngoscopy and upper gastrointestinal endoscopy to exclude organic disease.
      After 4 weeks of treatment with rabeprazole sodium (20 mg daily), the patients
      were divided into PPI-responsive and PPI-resistant groups. Then we investigated
      esophageal motility in the PPI-resistant group by a multichannel intraluminal
      impedance and manometry study. RESULTS: A total of 119 patients (55.6%) were
      resistant to PPI therapy, among whom 57 patients (47.9%) had abnormal esophageal
      motility. They included 36 patients (66.4%) with ineffective esophageal motility,
      9 patients (14.4%) with achalasia, 6 patients (9.6%) with diffuse esophageal
      spasm, 5 patients (8%) with nutcracker esophagus, and 1 patient (1.6%) with
      hypertensive lower esophageal sphincter. There were significant differences of
      upper esophageal sphincter pressure and esophageal body peristalsis between the
      patients with PPI-resistant LPRD and healthy controls matched for age and sex.
      CONCLUSION: Among patients with PPI-resistant LPRD, 47.9% had abnormal esophageal
      motility.

PMID- 22594307
TI  - Is assisted reproduction associated with abnormal placentation?
AB  - Artificial reproductive technologies (ART) and conception following a period of
      untreated infertility (>1 year) are independently associated with increased
      pregnancy complications in both singleton and multiple pregnancies. It is unknown
      if placental dysfunction associated with macroscopic and/or microscopic
      histological discrepancies might explain some of these variances. Our aim was to
      compare the histopathology of placentae from singleton pregnancies belonging to 3
      groups, as follows: conception as a result of ART; spontaneous conception (<1
      year of trying); and conception following untreated infertility (>1 year).
      Pathological examination of placentae from singleton pregnancies of nonsmoking,
      age-matched primiparous women with no significant medical history and no known
      uterine congenital anomalies was performed by a single pathologist blinded to the
      groups. Features were compared using analysis of variance and chi-square tests. A
      total of 89 placental pathology reports were available (control  =  39,
      infertility  =  17, ART  =  33). The mean placental thickness was significantly
      higher in the ART group when compared to the spontaneous conception group (P  = 
      0.02). There were significantly more placental hematomas in the ART group (P  = 
      0.04) compared to the other groups. There were no significant differences in
      rates of abnormal placental shapes or abnormal cord insertions. There were no
      statistically significant differences in the incidence of microscopic placental
      lesions, nor were there any statistically significant differences in the
      incidence of macroscopic and microscopic placental lesions between the
      infertility group and the other groups. Placentae of ART pregnancies show
      significantly increased thickness and a higher incidence of hematomas. Increased
      placental thickness has previously been linked to increased perinatal risk.

PMID- 22594308
TI  - Hydroxytyrosol attenuates peripheral neuropathy in streptozotocin-induced
      diabetes in rats.
AB  - Peripheral neuropathy is one of the most frequent and severe complications of
      diabetes. Hydroxytyrosol (HT), the major antioxidant polyphenolic compound of
      olive oil, has been investigated as a new potential treatment to counteract the
      progression of peripheral diabetic neuropathy in rats. An established model of
      streptozotocin-induced diabetes has been used. After confirmation of
      hyperglycemia, diabetic and nondiabetic animals were randomized to receive either
      a low dose or a high dose of HT, or the corresponding vehicle, for 6 weeks. At
      the end of the 6-week period of treatment, HT blunted plasma thiobarbituric acid
      reactive substances increase (p < 0.05) and significantly reduced nerve
      conduction velocity (p < 0.05) and thermal nociception impairment in diabetic
      rats (p < 0.05). Sciatic nerve Na(+), K(+)-ATPase activity reduction was also
      abolished by HT (p < 0.05). The present study provides evidence of the
      therapeutic potential of the natural substance hydroxytyrosol in the early stage
      of diabetic neuropathy. 

PMID- 22594309
TI  - Ligand-mediated modification of the electronic structure of CdSe quantum dots.
AB  - X-ray absorption spectroscopy and ab initio modeling of the experimental spectra
      have been used to investigate the effects of surface passivation on the
      unoccupied electronic states of CdSe quantum dots (QDs). Significant differences
      are observed in the unoccupied electronic structure of the CdSe QDs, which are
      shown to arise from variations in specific ligand-surface bonding interactions.

PMID- 22594310
TI  - Use of vascularized posterior rectus sheath allograft in pediatric multivisceral
      transplantation--report of two cases.
AB  - Restoring abdominal wall cover and contour in children undergoing bowel and
      multivisceral transplantation is often challenging due to discrepancy in size
      between donor and recipient, poor musculature related to birth defects and loss
      of abdominal wall integrity from multiple surgeries. A recent innovation is the
      use of vascularized posterior rectus sheath to enable closure of abdomen. We
      describe the application of this technique in two pediatric multivisceral
      transplant recipients--one to buttress a lax abdominal wall in a 22-month-old
      child with megacystis microcolon intestinal hypoperistalsis syndrome and another
      to accommodate transplanted viscera in a 10-month child with short bowel
      secondary to gastoschisis and loss of domain. This is the first successful report
      of this procedure with long-term survival. The procedure has potential
      application to facilitate difficult abdominal closure in both adults and
      pediatric liver and multivisceral transplantation.

PMID- 22594311
TI  - Legacy effects of aboveground-belowground interactions.
AB  - Root herbivory can greatly affect the performance of aboveground insects via
      changes in plant chemistry. These interactions have been studied extensively in
      experiments where aboveground and belowground insects were feeding on the same
      plant. However, little is known about how aboveground and belowground organisms
      interact when they feed on plant individuals that grow after each other in the
      same soil. We show that feeding by aboveground and belowground insect herbivores
      on ragwort (Jacobaea vulgaris) plants exert unique soil legacy effects, via
      herbivore-induced changes in the composition of soil fungi. These changes in the
      soil biota induced by aboveground and belowground herbivores of preceding plants
      greatly influenced the pyrrolizidine alkaloid content, biomass and aboveground
      multitrophic interactions of succeeding plants. We conclude that plant-mediated
      interactions between aboveground and belowground insects are also important when
      they do not feed simultaneously on the same plant.

PMID- 22594312
TI  - A novel nonsense mutation in HSD17B3 gene in a Tunisian patient with sexual
      ambiguity.
AB  - INTRODUCTION: 17beta-hydroxysteroid dehydrogenase type 3 (HSD17B3) isoenzyme is
      present almost exclusively in the testes and converts delta 4 androstenedione to
      testosterone. Mutations in the HSD17B3 gene cause HSD17B3 deficiency and result
      in 46,XY Disorders of Sex Development (46,XY DSD). AIM: This study aimed to
      present the clinical and biochemical features of a Tunisian patient who presented
      a sexual ambiguity orienting to HSD17B3 deficiency and to search for a mutation
      in the HSD17B3 gene by DNA sequencing. METHODS: Polymerase chain reaction (PCR)
      amplification and subsequent sequencing of all the coding exons of HSD17B3 gene
      were performed on genomic DNA from the patient, her family, and 50 controls.
      RESULTS: Genetic mutation analysis of the HSD17B3 gene revealed the presence of a
      novel homozygous nonsense mutation in the exon 9 (c.618 C>A) leading to the
      substitution p.C206X. The mutation p.C206X in the coding exons supports the
      hypothesis of HSD17B3 deficiency in our patient. CONCLUSION: The patient
      described in this study represented a new case of a rare form of 46,XY DSD,
      associated to a novel gene mutation of HSD17B3 gene. The screening of this
      mutation is useful for confirming the diagnosis of HSD17B3 deficiency and for
      prenatal diagnosis.

PMID- 22594314
TI  - Reactivity of the 1,3-beta-D-glucan assay during bacteraemia: limited evidence
      from a prospective study.
AB  - There are discrepancies in the retrospective studies published in literature of
      whether or not bacteraemia could lead to false positivity of 1,3-beta-D (BG)
      glucan assay. We performed, for the first time, a prospective study evaluating
      the role of bacterial bloodstream infection to the reactivity of BG assay. Twenty
      six episodes of bacteraemia that occurred in high-risk haematological patients
      were included in our study. Consecutive BG levels >80 pg ml(-1) were required for
      test positivity. Only 2 of 26 patients were BG positive - both with IFDs. Thus,
      we prospectively did not prove bacteraemia as the source of cross reactivity of
      BG assay in haematological patients.

PMID- 22594315
TI  - Anti-oxidized low-density lipoprotein (oxLDL) antibody levels are not related to
      increasing circulating oxLDL concentrations during the course of pregnancy.
AB  - PROBLEM: To address the question of whether the high levels of oxidative modified
      low-density lipoproteins (oxLDL) in pregnancy are opposed by an appropriate
      humoral autoimmune response providing anti-oxLDL autoantibodies in maternal serum
      of healthy women throughout gestation. METHOD OF STUDY: Blood was taken from 33
      patients at four different time points from early to late gestation and post
      partum. OxLDL and anti-oxLDL concentrations were measured by enzyme-linked
      immunosorbent assays. ANOVA was used for statistical evaluations followed by post
      hoc test with Bonferoni adjustment. RESULTS: Oxidized Low Density Lipoprotein
      concentrations increased while anti-oxLDL levels decreased significantly from
      early to late gestation. OxLDL was strongly positively correlated with LDL
      concentration and mildly negatively associated with anti-oxLDL levels. Estimating
      the status of oxidation by calculating oxLDL/LDL ratio revealed decreasing values
      with ongoing pregnancy. Multivariate analysis showed that anti-oxLDL levels were
      dependent on gestational age but neither on oxLDL levels nor on the oxLDL/LDL
      ratio. CONCLUSIONS: The results indicate that normal pregnancy is a well-balanced
      state of oxidative and anti-oxidative processes. However, we could not confirm a
      dependence of anti-oxLDL autoantibodies on oxLDL concentration. Whether or not
      the humoral immune system is involved in oxidative defence remains to be
      elucidated.

PMID- 22594316
TI  - Effect of surface energy on carbon dioxide hydrate formation.
AB  - In this work, the effect of the surface energy between the hydrate clusters and
      the aqueous phase on the hydrate formation of carbon dioxide was thoroughly
      investigated. Our results show that the threshold pressure for hydrate formation
      is less sensitive to the temperatures if the surface energy is not larger than 7
      mJ/m(2). However, the threshold pressure is very sensitive to the temperatures
      and increases significantly with the surface energy if it is over 7, 9, and 10
      mJ/m(2) for the temperatures of 279, 277.45, and 276 K, respectively. The value
      of the surface energy for the CO(2) hydrate/water system was determined as 9.3
      mJ/m(2) by comparing our results with the experimental data for stable CO(2)
      hydrate formation at the temperature range of 277.45-278.85 K and at pressures of
      55-165 bar. This value is very close to the recently reported value of 7.5 +/-
      1.4 mJ/m(2) from molecular simulation. A theoretical method was proposed for
      computing the induction time of hydrate formation adopting a composite of the
      time required for critical nuclei formation and their growth to a detectable
      size. By using this method, the surface energy was avoided in the induction time
      calculation and an average crystallite volume of 0.238 mm(3) at the induction
      time was derived based on the experimental data. It provides an approach for
      predicting the induction time for gas hydrate formation.

PMID- 22594313
TI  - Genome-wide recruitment to Polycomb-modified chromatin and activity regulation of
      the synovial sarcoma oncogene SYT-SSX2.
AB  - BACKGROUND: SYT-SSX is the oncogene associated with synovial sarcoma (SS), a stem
      cell disease. SYT-SSX is thought to be responsible for sarcoma initiation and
      development. It interacts with components of Polycomb and SWI/SNF complexes, the
      two epigenetic controllers that maintain the heritable status of differentiation
      specific genes in the stem/progenitor cell. Through these associations SYT-SSX is
      thought to alter gene expression programs by epigenetic mechanisms. Recently, we
      reported that SYT-SSX2 reprograms mesenchymal stem cells and myoblasts by
      dictating their commitment to the neural lineage while disrupting their normal
      differentiation. This reprogramming was due to the direct occupancy of proneural
      genes by the SYT-SSX2 nuclear complex. To gain a clear understanding of SYT-SSX2
      control of gene expression networks, we conducted a thorough genome-wide analysis
      to determine the mechanism of its recruitment and identify signature sets of
      epigenetic markers that would predict its targeting and transcriptional activity.
      RESULTS: SYT-SSX2 was recruited to distinct loci across all chromosomes, and an
      overwhelming number of Polycomb-modified sites enriched with the trimethylated
      histone H3 on lysine 27 (H3K27me3) formed the main recruiting module for SYT
      SSX2. Not all SYT-SSX2/H3K27me3-occupied genes had altered expression, denoting
      the requirement for additional signals upon oncogene binding. Differential
      binding and epigenetic patterns distinguished upregulated and downregulated
      genes. Most activated genes had SYT-SSX2 sites enriched with H3K27me3 within
      their body or near their transcription start site (TSS) whereas a majority of
      downregulated genes were characterized by SYT-SSX2/H3K27me3-rich regions at long
      range, or by modifications associated with transcription activation within the
      gene body or near the TSS. Hierarchical and functional clustering identified
      H3K27me3 as the dominant epigenetic marker associated with SYT-SSX2 binding and
      gene expression. Notably, this analysis revealed a cluster of upregulated
      neuronal genes densely covered by H3K27me3, consistent with programming toward
      the neural lineage by SYT-SSX2 observed previously. CONCLUSIONS: The data
      analysis revealed that Polycomb complexes or their modified chromatin and their
      stably silenced differentiation programs seem to be the main target for SYT-SSX2,
      suggesting that their perturbation is at the center of tumorigenesis driven by
      the oncogene. Further research into this mechanism is crucial to the full
      understanding of SS biology.

PMID- 22594317
TI  - 'The Little Purple Book', 2nd edition: Cell therapy and regenerative medicine
      glossary.

PMID- 22594320
TI  - Research highlights: Highlights from the latest articles in regenerative
      medicine.

PMID- 22594321
TI  - Stem cell training at Pasadena City College: providing pathways to careers in
      stem cell research.

PMID- 22594322
TI  - The ATMP Manufacturing Community (amc).

PMID- 22594323
TI  - Trends in the stem cells marketplace--report from Select Biosciences Stem Cells
      2012 Conference.

PMID- 22594324
TI  - Enhanced viability of corneal epithelial cells for efficient transport/storage
      using a structurally modified calcium alginate hydrogel.
AB  - AIMS: Therapeutic limbal epithelial stem cells could be managed more efficiently
      if clinically validated batches were transported for 'on-demand' use. MATERIALS &
      METHODS: In this study, corneal epithelial cell viability in calcium alginate
      hydrogels was examined under cell culture, ambient and chilled conditions for up
      to 7 days. RESULTS: Cell viability improved as gel internal pore size increased,
      and was further enhanced with modification of the gel from a mass to a thin disc.
      Ambient storage conditions were optimal for supporting cell viability in gel
      discs. Cell viability in gel discs was significantly enhanced with increases in
      pore size mediated by hydroxyethyl cellulose. CONCLUSION: Our novel methodology
      of controlling alginate gel shape and pore size together provides a more
      practical and economical alternative to established corneal tissue/cell storage
      methods.

PMID- 22594325
TI  - Cografting of carotid body cells improves the long-term survival, fiber outgrowth
      and functional effects of grafted dopaminergic neurons.
AB  - AIMS: A major limiting factor for cell therapy in Parkinson's disease is that the
      survival of grafted dopaminergic neurons is very poor, which may be improved by
      administration of GDNF, for which the carotid body is a good source. MATERIALS &
      METHODS: Rats with total unilateral dopaminergic denervation were grafted with a
      cell suspension of rat dopaminergic neuroblasts with or without cell aggregates
      from the rat carotid body. At 1, 2 and 3 months after grafting, the rats were
      tested in the cylinder and the rotometer and killed 4 months after grafting.
      RESULTS: We observed that the survival of dopaminergic neurons and graft-derived
      dopaminergic innervation were higher in rats that received mixed grafts. Both
      grafted groups showed complete recovery in the amphetamine-induced rotation test.
      However, rats with cografts performed significantly better in the cylinder test.
      CONCLUSION: Cografting of carotid body cells may constitute a useful strategy for
      cell therapy in Parkinson's disease.

PMID- 22594326
TI  - Subcellular preconditioning of stem cells: mito-Cx43 gene targeting is
      cytoprotective via shift of mitochondrial Bak and Bcl-xL balance.
AB  - AIM: To achieve mitochondria-specific expression of connexin-43 (Cx43) transgene
      for mitochondrial preconditioning in stem cells to improve their survival post
      transplantation during heart cell therapy. METHODS & RESULTS: Cx43- or GFP
      encoding adenoviral vectors with a mitochondrial targeting sequence were
      constructed for transduction of bone marrow Sca-1(+) cells (>90% transduction
      efficiency). Double-fluorescence immunostaining for cytochrome-c and Cx43
      supported by western blotting confirmed mitochondria-specific Cx43 expression in
      adenoviral-mito-Cx43-transduced cells ((Cx43)Sca-1(+)). (Cx43)Sca-1(+) showed
      improved survival under lethal oxygen-glucose deprivation culture conditions.
      (Cx43)Sca-1(+) showed an increased mitochondrial Bcl-xL:Bak ratio and reduced
      cytochrome-c release into cytosol with concomitantly abolished caspase-3
      activity. An in vivo study was performed such that 2 * 10(6) male (Cx43)Sca-1(+)
      or (GFP)Sca-1(+) cells were injected into a female rat model of acute myocardial
      infarction. DMEM-injected rats served as controls. On day 7 post-transplantation,
      4.3-fold higher survival of (Cx43)Sca-1(+) cells (p < 0.05 vs control) and
      reduced terminal deoxynucleotidyl transferase dUTP nick end labeling positivity
      in the left ventricle (LV) were observed. In comparison, LV ejection fraction
      (40.2 +/- 0.9%), LV fractional shortening (20.0 +/- 1.6%) and LV end diastolic
      dimension (6.5 +/- 0.3 mm) were observed in (GFP)Sca-1(+), and treatment with
      (Cx43)Sca-1(+) cells improved these parameters (47.6 +/- 2.5%, p < 0.05; 27.7 +/-
      1.2%, p < 0.05; and 5.6 +/- 0.1 mm, p < 0.05, respectively), along with
      concomitant reductions in infarction size (33.7 +/- 2.9% vs 39.8 +/- 1.4%; p <
      0.05). CONCLUSION: Mitochondria-targeted Cx43 expression is a novel approach to
      improve stem cell survival in the infarcted heart.

PMID- 22594327
TI  - Biofunctionalized quantum dots for live monitoring of stem cells: applications in
      regenerative medicine.
AB  - AIM: This study aimed to live monitor the degree of endothelial progenitor cell
      (EPC) integration onto tissue-engineering scaffolds by conjugating relevant
      antibodies to quantum dots (QDs). MATERIALS & METHODS: Biocompatible
      mercaptosuccinic acid-coated QDs were functionalized with two different
      antibodies to EPC (CD133 with QDs of 640 nm wavelength [lambda] and later-stage
      mature EPCs; and von Willebrand factor with QDs of lambda595 and lambda555 nm)
      using conventional carbomide and N-hydroxysuccinimide chemistry.
      Biofunctionalization was characterized with Fourier-transform infrared
      spectroscopy. Cell viability assays and gross morphology observations confirmed
      cytocompatibility and normal patterns of celluar growth. The antigens
      corresponding to each state of cell maturation were determined using a single
      excitation at lambda488 nm. RESULTS: The optimal concentrations of antibody-QD
      conjugates were biocompatible, hemocompatible and determined the state of EPC
      transformation to endothelial cells. CONCLUSION: Antibody-functionalized QDs
      suggest new applications in tissue engineering of polymer-based implants where
      cell integration can potentially be monitored without requiring the sacrifice of
      implants.

PMID- 22594328
TI  - Embryonic development of hematopoietic stem cells: implications for clinical use.
AB  - Hematopoietic stem cell (HSC) transplantation is an important treatment modality
      for hematological malignancies or to correct congenital immunodeficiency
      disorders. Several stem cell sources are currently applied clinically, with a
      recent increased application of umbilical cord blood. The low number of HSCs
      available, particularly in umbilical cord blood, is a limiting factor, and
      different lines of research are ongoing to circumvent this issue. In this review,
      we will describe the research strategies developed to expand adult HSCs in vitro
      and to generate new HSCs from pluripotent stem cell lines. We will also discuss
      the importance of studying the embryonic microenvironment since it allows both
      generation and extensive expansion of HSCs. Understanding the mechanisms that
      underlie HSC production, self-renewal and differentiation is necessary for the
      establishment of optimal in vitro HSC cultures, where a limitless and
      manipulatable resource of HSCs would be available for both clinical and
      fundamental research.

PMID- 22594329
TI  - Administration of growth factors for bone regeneration.
AB  - Growth factors (GFs) such as BMPs, FGFs, VEGFs and IGFs have significant impacts
      on osteoblast behavior, and thus have been widely utilized for bone tissue
      regeneration. Recently, securing biological stability for a sustainable and
      controllable release to the target tissue has been a challenge to practical
      applications. This challenge has been addressed to some degree with the
      development of appropriate carrier materials and delivery systems. This review
      highlights the importance and roles of those GFs, as well as their proper
      administration for targeting bone regeneration. Additionally, the in vitro and in
      vivo performance of those GFs with or without the use of carrier systems in the
      repair and regeneration of bone tissue is systematically addressed. Moreover,
      some recent advances in the utility of the GFs, such as using fusion technology,
      are also reviewed.

PMID- 22594330
TI  - Cellular replacement and regenerative medicine therapies in ischemic stroke.
AB  - Worldwide, tissue engineering and cellular replacement therapies are at the
      forefront of the regenerative medicine agenda, and researchers are addressing key
      diseases, including diabetes, stroke and neurological disorders. It is becoming
      evident that neurological cell therapy is a necessarily complex endeavor. The
      brain as a cellular environment is complex, with diverse cell populations,
      including specialized neurons (e.g., dopaminergic, motor and glutamatergic
      neurons), each with specific functions. The population also contains glial cells
      (astrocytes and oligodendrocytes) that offer the supportive network for neuronal
      function. Neurological disorders have wide and varied pathologies; they can
      affect predominantly one cell type or a multitude of cell types, which is the
      case for ischemic stroke. Both neuronal and glial cells are affected by stroke
      and, depending on the region of the brain affected, different specialized cells
      are influenced. This review will address currently available therapies and focus
      on the application and potential of cell replacement, including stem cells and
      immortalized cell line-derived neurons as regenerative therapies for ischemic
      stroke, addressing current advances and challenges ahead.

PMID- 22594332
TI  - Adipose-derived mesenchymal stromal cells for chronic myocardial ischemia
      (MyStromalCell Trial): study design.
AB  - Adipose tissue represents an abundant, accessible source of multipotent adipose
      derived stromal cells (ADSCs). Animal studies have suggested that ADSCs have the
      potential to differentiate in vivo into endothelial cells and cardiomyocytes.
      This makes ADSCs a promising new cell source for regenerative therapy to replace
      injured tissue by creating new blood vessels and cardiomyocytes in patients with
      chronic ischemic heart disease. The aim of this special report is to review the
      present preclinical data leading to clinical stem cell therapy using ADSCs in
      patients with ischemic heart disease. In addition, we give an introduction to the
      first-in-man clinical trial, MyStromalCell Trial, which is a prospective,
      randomized, double-blind, placebo-controlled study using culture-expanded ADSCs
      obtained from adipose-derived cells from abdominal adipose tissue and stimulated
      with VEGF-A(165) the week before treatment.

PMID- 22594331
TI  - Tissue-engineered vascular grafts for use in the treatment of congenital heart
      disease: from the bench to the clinic and back again.
AB  - Since the first tissue-engineered vascular graft (TEVG) was implanted in a child
      over a decade ago, growth in the field of vascular tissue engineering has been
      driven by clinical demand for improved vascular prostheses with performance and
      durability similar to an autologous blood vessel. Great strides were made in
      pediatric congenital heart surgery using the classical tissue engineering
      paradigm, and cell seeding of scaffolds in vitro remained the cornerstone of
      neotissue formation. Our second-generation bone marrow cell-seeded TEVG diverged
      from tissue engineering dogma with a design that induces the recipient to
      regenerate vascular tissue in situ. New insights suggest that neovessel
      development is guided by cell signals derived from both seeded cells and host
      inflammatory cells that infiltrate the graft. The identification of these signals
      and the regulatory interactions that influence cell migration, phenotype and
      extracellular matrix deposition during TEVG remodeling are yielding a next
      generation TEVG engineered to guide neotissue regeneration without the use of
      seeded cells. These developments represent steady progress towards our goal of an
      off-the-shelf tissue-engineered vascular conduit for pediatric congenital heart
      surgery.

PMID- 22594333
TI  - The UK relative to other single payer-dominated healthcare markets for
      regenerative medicine therapies.
AB  - The UK has for many years been considered by businesses, including those based in
      the UK, as at best a second market for the launch of innovative medical
      technology products. Historically, this has been attributed to the slow pace of
      adoption in its National Health Service (NHS). The NHS is perceived to be subject
      to cost containment, high levels of fragmentation and a lack of strategic
      incentives to resolve its key failings as a market. Canada and Sweden offer
      examples of different operating models of healthcare delivery in a single payer
      dominated market, and as a consequence, have evolved with different market
      characteristics. Together, these economies represent an important subsection of
      healthcare markets that are predominantly publically funded. This report examines
      the barriers to market entry for regenerative medicine products in these
      economies and attempts to evaluate the upcoming UK healthcare reforms in terms of
      impact on the regenerative medicine industry sector.

PMID- 22594334
TI  - Disclosure and management of research findings in stem cell research and banking:
      policy statement.
AB  - Prompted by an increased interest of both research participants and the patient
      advocacy community in obtaining information about research outcomes and on the
      use of their biological samples; the international community has begun to debate
      the emergence of an ethical 'duty' to return research results to participants.
      Furthermore, the use of new technologies (e.g., whole-genome and -exome
      sequencing) has revealed both genetic data and incidental findings with possible
      clinical significance. These technologies together with the proliferation of
      biorepositories, provide a compelling rationale for governments and scientific
      institutions to adopt prospective policies. Given the scarcity of policies in the
      context of stem cell research, a discussion on the scientific, ethical and legal
      implications of disclosing research results for research participants is needed.
      We present the International Stem Forum Ethics Working Party's Policy Statement
      and trust that it will stimulate debate and meet the concerns of researchers and
      research participants alike.

PMID- 22594336
TI  - Congenital nodule on the scapula.

PMID- 22594337
TI  - A case of worsening lipoatrophy in a 13 year-old girl.

PMID- 22594338
TI  - Persistent umbilical nodule.

PMID- 22594339
TI  - Epidemic of tinea corporis due to trichophyton mentagrophytes of rabbit origin.

PMID- 22594340
TI  - Mycoplasma pneumoniae-associated mucositis: by any other name is not so sweet.

PMID- 22594341
TI  - Delineating capillary malformations in the operating suite using white eyeliner
      pencil.

PMID- 22594342
TI  - Functional dosimetric metrics for predicting radiation-induced lung injury in non
      small cell lung cancer patients treated with chemoradiotherapy.
AB  - BACKGROUND: Radiation-induced lung injury (RILI) is an important dose-limiting
      toxicity during thoracic radiotherapy. The purpose of this study is to
      investigate single photon emission computed tomography (SPECT) perfusion-weighted
      functional dose-volume histogram (FDVH) for predicting RILI in non-small cell
      lung cancer (NSCLC) patients treated with definitive chemoradiotherapy. METHODS:
      Fifty-seven locally advanced NSCLC patients receiving chemoradiotherapy were
      enrolled prospectively. Patients had treatment scans and dose calculations to
      provide a standard dose-volume histogram (DVH). Fusion of SPECT and computed
      tomography scans provided perfusion-weighted FDVH and associated functional
      dosimetric parameters (relative volumes of functional lung receiving more than a
      threshold dose of 5 - 60 Gy at increments of 5 Gy [FV5 - FV60]). The predictive
      abilities of FDVH and DVH were calculated and compared based on the area under
      receiver operating characteristic (ROC) curve (AUC). RESULTS: The accumulative
      incidence of  >=  2 grade RILI was 19.3% with a median follow-up of 12 months.
      Univariate analysis showed that the functional (FV5 - FV60) and standard (V5 -
      V40) parameters were associated with RILI (all value of p < 0.05). Close
      correlations between a variety of functional and standard parameters were found.
      By ROC curve analysis, functional metrics (AUCs were 0.784 - 0.869) provided
      similarly (p value 0.233 - 1.000) predictive outcome to standard metrics (AUCs
      were 0.695 - 0.902) in lower - median dose level parameters (FV5 - FV40).
      However, FDVH seemed to add some predictive value in higher dose level, the best
      statistical significance for comparing FV60 with V60 was 0.693 vs. 0.511 (p =
      0.055). CONCLUSIONS: Functional metrics are identified as reliable predictors for
      RILI, however, this observation still needs to be further verified using a larger
      sample size.

PMID- 22594343
TI  - Hybrid peptides: direct transformation of alpha/alpha, beta-unsaturated gamma
      hybrid peptides to alpha/gamma-hybrid peptide 12-helices.
AB  - A smooth transformation of unusual planar structures of alpha/vinylogous hybrid
      peptides to ordered alpha/gamma(4)-hybrid peptide 12-helices and the
      stereochemical preferences of vinylogous amino acid residues in single crystals
      are studied.

PMID- 22594344
TI  - Comparative effect of angiotensin II type I receptor blockers and calcium channel
      blockers on laboratory parameters in hypertensive patients with type 2 diabetes.
AB  - BACKGROUND: Both angiotensin II type I receptor blockers (ARBs) and calcium
      channel blockers (CCBs) are widely used antihypertensive drugs. Many clinical
      studies have demonstrated and compared the organ-protection effects and adverse
      events of these drugs. However, few large-scale studies have focused on the
      effect of these drugs as monotherapy on laboratory parameters. We evaluated and
      compared the effects of ARB and CCB monotherapy on clinical laboratory parameters
      in patients with concomitant hypertension and type 2 diabetes mellitus. METHODS:
      We used data from the Clinical Data Warehouse of Nihon University School of
      Medicine obtained between Nov 1, 2004 and July 31, 2011, to identify cohorts of
      new ARB users (n = 601) and propensity-score matched new CCB users (n = 601),
      with concomitant mild to moderate hypertension and type 2 diabetes mellitus. We
      used a multivariate-adjusted regression model to adjust for differences between
      ARB and CCB users, and compared laboratory parameters including serum levels of
      triglyceride (TG), total cholesterol (TC), non-fasting blood glucose, hemoglobin
      A1c (HbA1c), sodium, potassium, creatinine, alanine aminotransferase (ALT),
      aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), hemoglobin and
      hematocrit, and white blood cell (WBC), red blood cell (RBC) and platelet (PLT)
      counts up to 12 months after the start of ARB or CCB monotherapy. RESULTS: We
      found a significant reduction of serum TC, HbA1c, hemoglobin and hematocrit and
      RBC count and a significant increase of serum potassium in ARB users, and a
      reduction of serum TC and hemoglobin in CCB users, from the baseline period to
      the exposure period. The reductions of RBC count, hemoglobin and hematocrit in
      ARB users were significantly greater than those in CCB users. The increase of
      serum potassium in ARB users was significantly greater than that in CCB users.
      CONCLUSIONS: Our study suggested that hematological adverse effects and
      electrolyte imbalance are greater with ARB monotherapy than with CCB monotherapy.

PMID- 22594345
TI  - Metabolism of ibuprofen in zebrafish larvae.
AB  - The application of zebrafish (Danio rerio) larvae to drug discovery assays and
      toxicity testing, and the occurrence of pharmaceuticals in the environment, has
      resulted in a need to understand the extent of the metabolic capabilities in the
      early life stages of this species. The aims of this study were to determine if
      zebrafish larvae absorbed, metabolized and excreted the model pharmaceutical,
      ibuprofen. Zebrafish larvae (72 h post fertilization) were exposed to ibuprofen
      (100 ug/L), (14)C-ibuprofen (100 ug/L) or a solvent control (ethanol) for <= 24
      h. Water samples and larval extracts were assessed for metabolites of ibuprofen
      using liquid chromatography mass spectrometry (LC-MS-MS). Fractions from the
      separation of the samples treated with (14)C-ibuprofen were collected after
      chromatography and analysed for (14)C content by scintillation counting.
      Assessment of larval extracts and water samples by LC-MS-MS at 24 h resulted in
      the identification of hydroxy-ibuprofen in both water samples and larval extracts
      (8.2 and 0.08% of the total detected (14)C, respectively). A second putative
      hydroxy-ibuprofen moiety was also observed in water samples at trace levels, and
      a third minor unknown metabolite was detected in larval extracts only by
      scintillation counting (0.02% of the total (14)C detected). This study provides
      evidence that zebrafish larvae can metabolize and excrete ibuprofen in a manner
      known to be cytochrome P450-dependent in mammals, and the similarity to the
      mammalian pathway supports the use of this system as a surrogate in toxicity and
      efficacy screening.

PMID- 22594346
TI  - Electroclinical biomarkers of early peripheral neurotoxicity from oxaliplatin.
AB  - Peripheral neuropathy is the principal dose-limiting side effect of chemotherapy
      with oxaliplatin. Early biomarkers of oxaliplatin-related neuropathy (ON) are
      important for guiding management and as outcomes for neuroprotective trials. We
      compared a number of clinical and neurophysiological techniques to identify early
      features of ON. Median nerve motor excitability testing, nerve conduction
      studies, vibration perception threshold (VPT) and clinical assessments were
      carried out on 17 patients and 105 controls. Neuropathy was graded using the
      total neuropathy score and National Cancer Institute Common Toxicity Criteria
      scales. Oxaliplatin causes a length-dependent sensory neuropathy. The most
      sensitive early marker of neuropathy was abnormal VPT in the foot followed by
      diminished sensory nerve action potential amplitudes. Median nerve excitability
      studies revealed no biologically significant effects of treatment on motor axons.
      VPT is an easily applicable and effective marker of neuropathy at low cumulative
      doses of oxaliplatin. Nerve excitability measures may be useful in predicting ON
      but motor studies do not reveal early cumulative changes following treatment with
      the drug.

PMID- 22594347
TI  - Functional bowel symptoms, fibromyalgia and fatigue: a food-induced triad?
AB  - OBJECTIVE: Patients with perceived food hypersensitivity typically present with
      multiple health complaints. We aimed to assess the severity of their intestinal
      and extra-intestinal symptoms. MATERIALS AND METHODS: In a prospective study, 84
      patients referred to our outpatient clinic for investigation of perceived food
      hypersensitivity were enrolled consecutively. Irritable bowel syndrome (IBS) was
      diagnosed according to the Rome III criteria. Severity and impact of bowel
      symptoms, fatigue and musculoskeletal pain were evaluated by using the following
      questionnaires: The IBS Severity Scoring System (IBS-SSS), the Fatigue Impact
      Scale (FIS), the FibroFatigue Scale (FFS), and visual analogue scales (VAS) for
      scoring of musculoskeletal pain. RESULTS: All but one patient were diagnosed with
      IBS, 58% with severe symptoms. Extra-intestinal symptoms suggestive of chronic
      fatigue and fibromyalgia were demonstrated in 85% and 71%, respectively. Neither
      IgE-mediated food allergy nor organic pathology could explain the patients'
      symptoms. Nevertheless, malabsorption of fat was demonstrated in 10 of 38
      subjects. CONCLUSIONS: Perceived food hypersensitivity may be associated with
      severe, debilitating illness. The comorbid triad of IBS, chronic fatigue, and
      musculoskeletal pain is striking and may point to a common underlying cause.

PMID- 22594348
TI  - Molecular cloning, characterization of porcine IZUMO1, an IgSF family member.
AB  - IZUMO1, belonging to the family of mammalian immunoglobulin proteins, has been
      well characterized in the mouse. Here, we describe the molecular cloning and
      expression analysis of porcine IZUMO1 (pIZUMO1). Partial sequence information
      published in the National Center for Biotechnology Information (NCBI) database
      was used to generate the full-length sequence for IZUMO1 using rapid
      amplification of cDNA ends (RACE). A search of the porcine genomic sequence in
      the NCBI database identified a bacterial artificial chromosome (BAC) encoding the
      pIZUMO1 gene. This BAC is derived from porcine chromosome 6 and is syntenic with
      the corresponding regions of mouse, bovine, and human genomes encoding the IZUMO
      gene family. This BAC was found to encode an IZUMO1 protein with a predicted
      amino acid sequence having high similarity with mouse and human IZUMO1. Western
      blot analysis of proteins from porcine tissues indicated that pIZUMO1 was
      specifically expressed in the sperm. Furthermore, to confirm whether pIZUMO1
      forms complexes, we overexpressed pIZUMO1 in HEK293 cells. The recombinant
      pIZUMO1 from cell extracts was found to form complexes. Our finding suggests that
      pIZUMO1 forms homodimeric complex on the sperm membrane. Furthermore, an IVF
      inhibition assay with an antibody for the porcine IZUMO1 Ig-like domain showed
      that Ig-like domain effectively prevented pig sperm-egg interactions.

PMID- 22594349
TI  - Developing interprofessional simulation in the undergraduate setting: experience
      with five different professional groups.
AB  - This article reports our experience of developing half-day sessions of
      interprofessional simulation for pre-qualifying students from medicine, nursing,
      physiotherapy, radiography and operating department practice. One hundred and
      ninety-one students participated in a session. A questionnaire consisting of
      Likert type, visual analog and open comment questions explored their perceptions
      of the sessions as a learning experience, their attitudes toward
      interprofessional learning and the factors important for good patient care either
      after, or before and after, the session, as appropriate. Responses were analyzed
      using descriptive statistics, statistical tests for difference or thematic
      coding. Our data suggest that routine scenarios following patient journeys offer
      such students valuable educational experiences. In order to maximize the
      educational value of such sessions, particular attention should be paid to the
      benefits anticipated for individual professions, as well as those for all groups;
      to the wider educational context in which sessions lie and to the careful
      management of debriefing. A collaborative approach to the development of these
      increasingly popular but time and resource intensive educational interventions is
      advantageous for both staff and students.

PMID- 22594350
TI  - Spatial heterogeneity of eukaryotic microbial communities in an unstudied
      geothermal diatomaceous biological soil crust: Yellowstone National Park, WY,
      USA.
AB  - Knowledge of microbial communities and their inherent heterogeneity has
      dramatically increased with the widespread use of high-throughput sequencing
      technologies, and we are learning more about the ecological processes that
      structure microbial communities across a wide range of environments, as well as
      the relative scales of importance for describing bacterial communities in natural
      systems. Little work has been carried out to assess fine-scale eukaryotic
      microbial heterogeneity in soils. Here, we present findings from a bar-coded 18S
      rRNA survey of the eukaryotic microbial communities in a previously unstudied
      geothermal diatomaceous biological soil crust in Yellowstone National Park, WY,
      USA, in which we explicitly compare microbial community heterogeneity at the
      particle scale within soil cores. Multivariate analysis of community composition
      showed that while subsamples from within the same soil core clustered together,
      community dissimilarity between particles in the same core was high. This study
      describes a novel soil microbial environment and also adds to our growing
      understanding of microbial heterogeneity and the scales relevant to the study of
      soil microbial communities.

PMID- 22594351
TI  - Patterns and preexisting risk factors of 30-day mortality after a primary
      discharge diagnosis of syncope or near syncope.
AB  - OBJECTIVES: The risk of short-term mortality after an emergency department (ED)
      visit for syncope is poorly understood, resulting in prognostic uncertainty and
      frequent hospital admission. The authors determined patterns and risk factors for
      short-term mortality after a diagnosis of syncope or near syncope to aid in
      medical decision-making. METHODS: A retrospective cohort study was performed of
      adult members of Kaiser Permanente Southern California seen at 11 EDs from 2002
      to 2006 with a primary discharge diagnosis of syncope or near syncope
      (International Classification of Diseases, Ninth Revision [ICD-9] 780.2). The
      outcome was 30-day mortality. Proportional hazards time-to-event regression
      models were used to identify risk factors. RESULTS: There were 22,189
      participants with 23,951 ED visits, resulting in 307 deaths by 30 days. A
      relatively lower risk of death was reached within 2 weeks for ages 18 to 59
      years, but not until 3 months or more for ages 60 and older. Preexisting
      comorbidities associated with increased mortality included heart failure (hazard
      ratio [HR] = 14.3 in ages 18 to 59 years, HR = 3.09 in ages 60 to 79 years, HR =
      2.34 in ages 80 years plus; all p < 0.001), diabetes (HR = 1.49, p = 0.002),
      seizure (HR = 1.65, p = 0.016), and dementia (HR = 1.41, p = 0.034). If the index
      visit followed one or more visits for syncope in the previous 30 days, it was
      associated with increased mortality (HR = 1.86, p = 0.024). Absolute risk of
      death at 30 days was under 0.2% in those under 60 years without heart failure and
      more than 2.5% across all ages in those with heart failure. CONCLUSIONS: The low
      risk of death after an ED visit for syncope or near syncope in patients younger
      than 60 years old without heart failure may be helpful when deciding who to admit
      for inpatient evaluation. The presence of one or more comorbidities that predict
      death and a prior visit for syncope should be considered in clinical decisions
      and risk stratification tools for patients with syncope. Close clinical follow-up
      seems advisable in patients 60 years and older due to a prolonged risk of death.

PMID- 22594352
TI  - Factors associated with no or delayed linkage to care in newly diagnosed human
      immunodeficiency virus (HIV)-1-infected patients identified by emergency
      department-based rapid HIV screening programs in two urban EDs.
AB  - OBJECTIVES: The objective was to describe the proportions of successful linkage
      to care (LTC) and identify factors associated with LTC among newly diagnosed
      human immunodeficiency virus (HIV)-positive patients, from two urban emergency
      department (ED) rapid HIV screening programs. METHODS: This was a retrospective
      analysis of programmatic data from two established urban ED rapid HIV screening
      programs between November 2005 and October 2009. Trained HIV program assistants
      interviewed all patients tested to gather risk behavior data using a structured
      data collection instrument. Reactive results were confirmed by Western blot
      testing. Patients were provided with scheduled appointments at HIV specialty
      clinics at the institutions where they tested positive within 30 days of their ED
      visit. "Successful" LTC was defined as attendance at the HIV outpatient clinic
      within 30 days after HIV diagnosis, in accordance with the ED National HIV
      Testing Consortium metric. "Any" LTC was defined as attendance at the outpatient
      HIV clinic within 1 year of initial HIV diagnosis. Multivariate logistic
      regression was performed to determine factors associated with any LTC or
      successful LTC. RESULTS: Of the 15,640 tests administered, 108 (0.7%) were newly
      identified HIV-positive cases. Nearly half (47.2%) of the patients had been
      previously tested for HIV. Successful LTC occurred in 54% of cases; any LTC
      occurred in 83% of cases. In multivariate analysis, having public medical
      insurance and being self-pay were negatively associated with successful LTC (odds
      ratio [OR] = 0.33, 95% confidence interval [CI] = 0.12 to 0.96; OR = 0.34, 95% CI
      = 0.13 to 0.89, respectively); being female and having previously tested for HIV
      was negatively associated with any LTC (OR = 0.30, 95% CI = 0.10 to 0.93; OR =
      0.23, 95% CI = 0.07 to 0.77, respectively). CONCLUSIONS: In spite of dedicated
      resources for arranging LTC in the ED HIV testing programs, nearly 50% of
      patients did not have successful LTC (i.e., LTC occurred at >30 days), although
      >80% of patients were LTC within 1 year of initial diagnosis. Further evaluation
      of the barriers associated with successful LTC for those with public insurance
      and self-pay is warranted.

PMID- 22594353
TI  - Intralipid fat emulsion decreases respiratory failure in a rat model of parathion
      exposure.
AB  - BACKGROUND: Therapies exist for acute organophosphate (OP) exposure but mortality
      rates remain high (10% to 20%). Currently, treatment focuses on reversing the
      resultant cholinergic excess effects through the use of atropine. Intralipid fat
      emulsion (IFE) has been used to treat lipophilic drug ingestions and
      theoretically would be beneficial for some OP agents. OBJECTIVES: The hypothesis
      was that IFE would decrease the acute respiratory depressant effects following
      lethal OP exposure using a lipophilic OP agent (parathion). METHODS: The authors
      used a previously validated animal model of OP poisoning with detailed
      physiologic respiratory recordings. The model consisted of Wistar rats
      anesthetized but spontaneously breathing 100% oxygen. Airflow, respiratory rate,
      tidal volume, mean arterial pressure, and pulse rate were digitally recorded for
      120 minutes following OP exposure or until respiratory failure. Three study
      groups included parathion alone (n = 6), parathion and IFE 5 minutes after
      poisoning (n = 6), and parathion and IFE 20 minutes after poisoning (n = 6). In
      all groups, parathion was given as a single oral dose of 54 mg/kg (four times the
      rat oral 50% population lethal dose [LD(50) ]). Three boluses of IFE (15
      mg/kg/min) were given over 3 minutes, 20 minutes apart, starting either 5 or 20
      minutes after poisoning. Timing of IFE was based on parathion kinetics. In one
      study group IFE was initiated 5 minutes after poisoning to coincide with initial
      absorption of parathion. In another study group IFE was given at 20 minutes to
      coincide with peak intravenous (IV) parathion concentration. Primary outcome was
      percentage of animals with apnea. Secondary outcome was time to apnea. RESULTS:
      Animals exposed to parathion alone demonstrated a steady decline in respiratory
      rate and tidal volume postexposure, with apnea occurring a mean of 51.6 minutes
      after poisoning (95% confidence interval [CI] = 35.8 to 53.2 minutes). Animals
      treated with IFE 5 minutes postexposure demonstrated no difference in mean time
      to apnea (44.5 minutes vs. 51.6 minutes, p = 0.29) or number of animals with
      respiratory arrest (100% vs. 100%, p = 1.00). Animals treated with IFE 20 minutes
      postexposure demonstrated a significantly prolonged mean time to apnea (95.3
      minutes vs. 51.6 minutes, p = 0.002), but there was no difference in number of
      animals with respiratory arrest (100% vs. 66.7%, p = 0.45). CONCLUSIONS: All
      animals exposed to 4 * LD(50) of oral parathion demonstrate apnea and respiratory
      arrest. IFE given immediately after oral parathion does not prolong time to
      apnea. IFE given 20 minutes after oral exposure to parathion decreases the acute
      effects of the OP and prolongs the time to apnea.

PMID- 22594354
TI  - A new improved accelerated diagnostic protocol safely identifies low-risk
      patients with chest pain in the emergency department.
AB  - OBJECTIVES: To assess whether the accelerated diagnostic protocol (ADP) studied
      in the Asia Pacific Evaluation of Chest Pain Trial (ASPECT) could be optimized to
      effectively risk stratify patients with symptoms suggestive of acute coronary
      syndrome (ACS) and allow early discharge of very-low-risk patients. METHODS:
      Patients presenting to the emergency department (ED) with chest pain were
      prospectively enrolled between November 2007 and April 2010. Blood samples were
      analyzed at 0 and 2 hours postpresentation with a point-of-care multimarker panel
      (POC-MMP; troponin I [TnI], creatine kinase myocardial band [CKMB] isoenzyme
      fraction, and myoglobin) and a high-sensitivity cardiac troponin T assay (hsTnT).
      Patients received standard care. The original ADP (Thrombolysis in Myocardial
      Infarction [TIMI] risk score = 0, no ischemic electrocardiogram [ECG] changes,
      and the multimarker panel negative) was compared with an ADP using the point of
      care TnI only, hsTnT only, or TIMI risk score = 0 to 1. Primary outcome was ACS
      within 30 days. RESULTS: Of the 1,000 patients recruited, 362 (36.2%) had ACS.
      There were 12.3% identified as low risk by the original ADP with a sensitivity
      for ACS of 99.2% (95% confidence interval [CI] = 97.5% to 99.8%). The ADP with
      the point of care TnI only or hsTnT had the same sensitivity, but identified more
      patients for discharge (15.0% vs. 12.3%). Including patients with a TIMI risk
      score of 1 identified more patients as low risk (19.7%), but with a lower
      sensitivity (97.0% vs. 99.2%). CONCLUSIONS: An ADP consisting of a TIMI risk
      score of 0, no new ECG changes, and negative troponin at 0 and 2 hours
      postpresentation safely identifies patients at low risk of ACS, in whom discharge
      without further evaluation can be considered.

PMID- 22594355
TI  - Combination of copeptin and troponin assays to rapidly rule out non-ST elevation
      myocardial infarction in the emergency department.
AB  - OBJECTIVES: The aim of this study was to analyze the diagnostic accuracy and the
      clinical usefulness of the combination of troponin I (cTnI) and copeptin measured
      at presentation with an automated assay to rapidly rule out non-ST elevation
      myocardial infarction (NSTEMI) in patients with suspected cardiac chest pain
      presenting to an emergency department (ED). METHODS: This study was an ancillary
      analysis of a prospective observational study. Copeptin and cTnI levels were
      sampled at presentation in 641 consecutive patients admitted to the ED for chest
      pain with onset within the last 12 hours and without ST elevation on a 12-lead
      electrocardiogram (ECG). Copeptin was measured with an automated assay and
      troponin with conventional assay. The performance of a combination of cTnI and
      copeptin for NSTEMI diagnosis was studied, the clinical utility was assessed by
      multivariate analysis, and an area under the curve (AUC) calculation was used to
      determine accuracy. RESULTS: NSTEMI was diagnosed in 95 patients (15%). The
      sensitivity and negative predictive value (NPV) of the combination of copeptin
      and cTnI measures were 90.4% (95% confidence interval [CI] = 88.2% to 92.7%) and
      97.6% (95% CI = 96.4% to 98.7%) versus 55.3% (95% CI = 51.5% to 59.2%) and 92.8%
      (95% CI = 90.8% to 94.8%) with cTnI alone. The AUC of the combination of copeptin
      and cTnI was 0.89 (95% CI = 0.85% to 0.92%) and was significantly higher than the
      AUC of cTnI alone (0.77, 95% CI = 0.72% to 0.82%, p < 0.05). The patient
      classification was slightly improved when copeptin was added to the usual
      diagnostic tools used for NSTEMI management. CONCLUSIONS: In this study,
      determination of copeptin, in addition to cTnI, improves early diagnostic
      accuracy of NSTEMI. However, the sensitivity of this combination even using a
      conventional troponin assay remains insufficient to safely rule out NSTEMI at the
      time of presentation.

PMID- 22594356
TI  - Effect of testing and treatment on emergency department length of stay using a
      national database.
AB  - OBJECTIVES: Testing and treatment are essential aspects of the delivery of
      emergency care. Recognition of the effects of these activities on emergency
      department (ED) length of stay (LOS) has implications for administrators planning
      efficient operations, providers, and patients regarding expectations for length
      of visit; researchers in creating better models to predict LOS; and policy-makers
      concerned about ED crowding. METHODS: A secondary analysis was performed using
      years 2006 through 2008 of the National Hospital Ambulatory Medical Care Survey
      (NHAMCS), a nationwide study of ED services. In univariate and bivariate
      analyses, the authors assessed ED LOS and frequency of testing (blood test,
      urinalysis, electrocardiogram [ECG], radiograph, ultrasound, computed tomography
      [CT], or magnetic resonance imaging [MRI]) and treatment (providing a medication
      or performance of a procedure) according to disposition (discharged or admitted
      status). Two sets of multivariable models were developed to assess the
      contribution of testing and treatment to LOS, also stratified by disposition. The
      first was a series of logistic regression models to provide an overview of how
      testing and treatment activity affects three dichotomized LOS cutoffs at 2, 4,
      and 6 hours. The second was a generalized linear model (GLM) with a log-link
      function and gamma distribution to fit skewed LOS data, which provided time costs
      associated with tests and treatment. RESULTS: Among 360 million weighted ED
      visits included in this analysis, 227 million (63%) involved testing, 304 million
      (85%) involved treatment, and 201 million (56%) involved both. Overall, visits
      with any testing were associated with longer LOS (median = 196 minutes;
      interquartile range [IQR] = 125 to 305 minutes) than those with any treatment
      (median = 159 minutes; IQR = 91 to 262 minutes). This difference was more
      pronounced among discharged patients than admitted patients. Obtaining a test was
      associated with an adjusted odds ratio (OR) of 2.29 (95% confidence interval [CI]
      = 1.86 to 2.83) for experiencing a more than 4-hour LOS, while performing a
      treatment had no effect (adjusted OR = 0.84; 95% CI = 0.68 to 1.03). The most
      time-costly testing modalities included blood test (adjusted marginal effects on
      LOS = +72 minutes; 95% CI = 66 to 78 minutes), MRI (+64 minutes; 95% CI = 36 to
      93 minutes), CT (+59 minutes; 95% CI = 54 to 65 minutes), and ultrasound (US; +56
      minutes; 95% CI = 45 to 67 minutes). Treatment time costs were less substantial:
      performing a procedure (+24 minutes; 95% CI = 20 to 28 minutes) and providing a
      medication (+15 minutes; 95% CI = 8 to 21 minutes). CONCLUSIONS: Testing and less
      substantially treatment were associated with prolonged LOS in the ED,
      particularly for blood testing and advanced imaging. This knowledge may better
      direct efforts at streamlining delivery of care for the most time-costly
      diagnostic modalities or suggest areas for future research into improving
      processes of care. Developing systems to improve efficient utilization of these
      services in the ED may improve patient and provider satisfaction. Such practice
      improvements could then be examined to determine their effects on ED crowding.

PMID- 22594357
TI  - Children injured by violence in the United States: emergency department
      utilization, 2000-2008.
AB  - OBJECTIVES: Children victimized by violence are often treated in the emergency
      department (ED). However, our understanding of the magnitude and financial costs
      of this patient population is inadequate. The authors examined the scope, risk
      factors for, and financial cost of ED visits for intentional injury in children
      in the United States over time. METHODS: Using data from the National Hospital
      Ambulatory Medical Care Survey (NHAMCS) from 2000 through 2008, the records of
      children aged 0 to 17 years evaluated in an ED for intentional injuries were
      examined. Nationally representative rates of ED visits for intentional injuries,
      the proportion of ED visits accounted for by children with intentional injuries,
      and risk factors for intentional injury visits were calculated. The Web-based
      Injury Statistics Query and Reporting System (WISQARS) Cost of Injury Reports was
      used to generate the medical costs accrued by intentional injuries in children.
      RESULTS: Almost 340,000 children were treated in U.S. EDs each year from 2000
      through 2008 for intentional injuries, comprising 1.2% (95% confidence interval
      [CI] = 1.1% to 1.4%) of all U.S. pediatric ED visits. The rate of ED visits for
      violent injuries has not changed over time. In 2008, 49 children per 10,000 (95%
      CI = 36 to 61) were treated in the ED for a violent injury. In a multivariate
      model, increasing age, residing in a metropolitan area, African American race,
      and the lack of private insurance were independent predictors of intentional
      injury visits among children. In 2005, the aggregate medical cost of
      intentionally inflicted injuries in children in the United States was $765
      million. CONCLUSIONS: ED visits among children for violent injury still represent
      an important clinical, public health, and economic challenge. The ED could be
      considered as a potential venue for prevention and intervention efforts.

PMID- 22594358
TI  - The association between insurance status and emergency department disposition of
      injured California children.
AB  - OBJECTIVES: This study examined the relationship between insurance status and
      emergency department (ED) disposition of injured California children. METHODS:
      Multivariate regression models were built using data obtained from the 2005
      through 2009 California Office of Statewide Health Planning and Development
      (OSHPD) data sets for all ED visits by injured children younger than 19 years of
      age. RESULTS: Of 3,519,530 injury-related ED visits, 52% were insured by private,
      and 36% were insured by public insurance, while 11% of visits were not insured.
      After adjustment for injury characteristics and demographic variables, publicly
      insured children had a higher likelihood of admission for mild, moderate, and
      severe injuries compared to privately insured children (mild injury adjusted odds
      ratio [AOR] = 1.36, 95% confidence interval [CI] = 1.34 to 1.39; moderate and
      severe injury AOR = 1.34, 95% CI = 1.28 to 1.41). However, uninsured children
      were less likely to be admitted for mild, moderate, and severe injuries compared
      to privately insured children (mild injury AOR = 0.63, 95% CI = 0.61 to 0.66;
      moderate and severe injury AOR = 0.50, 95% CI = 0.46 to 0.55). While publicly
      insured children with moderate and severe injuries were as likely as privately
      insured children to experience an ED death (AOR = 0.91, 95% CI = 0.70 to 1.18),
      uninsured children with moderate and severe injuries were more likely to die in
      the ED compared to privately insured children (AOR = 3.11, 95% CI = 2.38 to
      4.06). CONCLUSIONS: Privately insured, publicly insured, and uninsured injured
      children have disparate patterns of ED disposition. Policy and clinical efforts
      are needed to ensure that all injured children receive equitable emergency care.

PMID- 22594359
TI  - Classification of emergency departments according to their services for community
      dwelling seniors.
AB  - OBJECTIVES: The goal was to develop a classification of emergency departments
      (EDs) based on their organization of services for seniors discharged to the
      community. METHODS: This was a secondary analysis of data collected in a survey
      of key informants (chief physicians and head nurses) in EDs in Quebec on the
      organization of services for community-dwelling seniors discharged to the
      community. Organizational characteristics were classified a priori in the
      following three categories: 1) availability of human resources, 2) care
      processes, and 3) links to community services. A multifactorial analysis (MFA)
      was used to analyze the variables by category and globally, thus investigating
      not only the relationships between variables within each category, but also the
      relationships between different categories. The authors then proceeded to
      classify EDs using Ward's method (hierarchical ascendant classification) applied
      to reduced data dimensions. RESULTS: The sample consisted of 103 EDs. Analyses
      were carried out on data from the 68 (66%) of these EDs that supplied complete
      data. These 68 EDs did not differ in terms of their size or geographical location
      from the 35 other departments that supplied incomplete or no data. We identified
      three groups of EDs: most specialized (with regard to internal staff and care
      processes) and less community-oriented (n = 12), moderately specialized and less
      community-oriented (n = 28), and least specialized and more community-oriented (n
      = 28). CONCLUSIONS: This classification of EDs with respect to their organization
      of services for community-dwelling seniors may be helpful to those planning
      services, to decision-makers, and to researchers. The three groups of EDs
      identified in this study represent three types of organizations with differing
      assets and limitations. The generalizability of these groups to other settings
      and the implications for patient outcomes should be investigated.

PMID- 22594360
TI  - National study of antibiotic use in emergency department visits for pneumonia,
      1993 through 2008.
AB  - OBJECTIVES: The Infectious Disease Society of America (IDSA) and American
      Thoracic Society (ATS) developed guidelines for the management of community
      acquired pneumonia (CAP); however, there are sparse data on actual rates of
      antibiotic use in the emergency department (ED) setting. METHODS: Data were
      obtained from the National Hospital Ambulatory Medical Care Survey (NHAMCS) for
      ED visits during 1993 through 2008 for adults with a diagnosis of pneumonia.
      RESULTS: During the study period there were an estimated 23,252,000 pneumonia
      visits, representing 1.8% of all ED visits. The visit rate for pneumonia during
      this 16-year period may have increased (p trend = 0.055). Overall, 66% of adult
      patients with a primary diagnosis of pneumonia had documentation of an antibiotic
      administered while in the ED. There was an increase in antibiotic administration
      for adults with pneumonia from 1993 through 2008 (49% to 80%; p trend < 0.001).
      Specifically, there was an increase in use of macrolides from 1993 to 2006 (20%
      to 30%, p trend < 0.001) and a marked increase in use of quinolones from 0% to
      39% from 1993 through 2008 (p trend < 0.001). Penicillin and cephalosporin use
      remained stable. Use of an antibiotic consistent with 2007 IDSA/ATS guidelines
      increased from 22% (95% confidence interval [CI] = 16% to 27%) of cases in 1993
      1994 to 68% (95% CI = 63% to 73%) of cases in 2007-2008 (p trend < 0.001).
      CONCLUSIONS: ED visit rates for pneumonia increased slightly from 1993 through
      2008. Although antibiotic administration in the ED has increased for adults with
      CAP, guideline-concordant antibiotics may not be consistently administered.

PMID- 22594361
TI  - Predicting emergency department volume using forecasting methods to create a
      "surge response" for noncrisis events.
AB  - OBJECTIVES: This study investigated whether emergency department (ED) variables
      could be used in mathematical models to predict a future surge in ED volume based
      on recent levels of use of physician capacity. The models may be used to guide
      decisions related to on-call staffing in non-crisis-related surges of patient
      volume. METHODS: A retrospective analysis was conducted using information
      spanning July 2009 through June 2010 from a large urban teaching hospital with a
      Level I trauma center. A comparison of significance was used to assess the impact
      of multiple patient-specific variables on the state of the ED. Physician capacity
      was modeled based on historical physician treatment capacity and productivity.
      Binary logistic regression analysis was used to determine the probability that
      the available physician capacity would be sufficient to treat all patients
      forecasted to arrive in the next time period. The prediction horizons used were
      15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, and 12 hours. Five
      consecutive months of patient data from July 2010 through November 2010, similar
      to the data used to generate the models, was used to validate the models.
      Positive predictive values, Type I and Type II errors, and real-time accuracy in
      predicting noncrisis surge events were used to evaluate the forecast accuracy of
      the models. RESULTS: The ratio of new patients requiring treatment over total
      physician capacity (termed the care utilization ratio [CUR]) was deemed a robust
      predictor of the state of the ED (with a CUR greater than 1 indicating that the
      physician capacity would not be sufficient to treat all patients forecasted to
      arrive). Prediction intervals of 30 minutes, 8 hours, and 12 hours performed best
      of all models analyzed, with deviances of 1.000, 0.951, and 0.864, respectively.
      A 95% significance was used to validate the models against the July 2010 through
      November 2010 data set. Positive predictive values ranged from 0.738 to 0.872,
      true positives ranged from 74% to 94%, and true negatives ranged from 70% to 90%
      depending on the threshold used to determine the state of the ED with the 30
      minute prediction model. CONCLUSIONS: The CUR is a new and robust indicator of an
      ED system's performance. The study was able to model the tradeoff of longer time
      to response versus shorter but more accurate predictions, by investigating
      different prediction intervals. Current practice would have been improved by
      using the proposed models and would have identified the surge in patient volume
      earlier on noncrisis days.

PMID- 22594362
TI  - A medical simulation-based educational intervention for emergency medicine
      residents in neonatal resuscitation.
AB  - OBJECTIVES: The objective was to determine if a medical simulation-based neonatal
      resuscitation educational intervention is a more effective teaching method than
      the current emergency medicine (EM) curriculum at one 4-year EM residency
      program. METHODS: A prospective, randomized study of second-, third-, and fourth
      year EM residents was performed. Of 36 potential subjects, 27 residents were
      enrolled. Each resident was assessed at baseline and after the intervention using
      1) a questionnaire to evaluate confidence in leading adult, pediatric, and
      neonatal resuscitation and prior neonatal resuscitation experience and 2) a
      neonatal resuscitation simulation scenario in which each participant was the code
      leader to evaluate knowledge and skills. Assessments were digitally recorded and
      reviewed independently by two Neonatal Resuscitation Program (NRP) instructors
      using a validated neonatal resuscitation scoring tool. Controls (15 participants)
      received the current EM curriculum. The intervention group (12 participants)
      experienced an educational session, which incorporated didactics, skills station,
      and medical simulation about neonatal resuscitation. Outcomes measured included
      changes in overall neonatal resuscitation score, number of critical actions, time
      to initial steps of neonatal resuscitation, and changes in confidence level
      leading neonatal resuscitation. RESULTS: Baseline neonatal resuscitation scores
      were similar for the control and intervention groups. At the final assessment,
      the intervention group's neonatal resuscitation score improved (p = 0.016) and
      the control group's score did not. The intervention group performed 2.31 more
      critical actions overall and the time to achieve warming (p = 0.0002), drying (p
      < 0.0001), tactile stimulation (p = 0.002), and placing a hat on the patient (p
      <0.0001) were also improved compared to controls. At the baseline assessment, 80%
      of the control group and 75% of the intervention group reported being "not at all
      confident" in leading neonatal resuscitation. At the final assessment, the
      proportion of residents who were "not at all confident" leading neonatal
      resuscitation decreased to 35% in the intervention group compared to 67% of the
      control group. The majority of the intervention group (65%) reported an increased
      level of confidence in leading neonatal resuscitation. CONCLUSIONS: Medical
      simulation can be an effective tool to assess the knowledge and skills of EM
      residents in neonatal resuscitation. Our simulation-based educational
      intervention significantly improved EM residents' knowledge and performance of
      the critical initial steps in neonatal resuscitation. A medical simulation-based
      educational intervention may be used to improve EM residents' knowledge and
      performance with neonatal resuscitation.

PMID- 22594363
TI  - A porcine pneumothorax model for teaching ultrasound diagnostics.
AB  - OBJECTIVES: Ultrasound (US) is a sensitive diagnostic tool for detecting
      pneumothorax (PTX), but methods are needed to optimally teach this technique
      outside of direct patient care. In training and research settings, porcine PTX
      models are sometimes used, but the description of the PTX topography in these
      models is lacking. The study purpose was to define the distribution of air using
      the reference imaging standard computed tomography (CT), to see if pleural
      insufflation of air into a live anaesthetized pig truly imitates a PTX in an
      injured patient. METHODS: A unilateral catheter was inserted into one pleural
      cavity of each of 20 pigs, and 500 mL of air was insufflated. After a complete
      thoracic CT scan, the anterior, lateral, medial, basal, apical, and posterior
      components of the PTXs were compared. The amount of air in each location was
      quantified by measuring the distance from the lung edge to the chest wall (LE
      CW). A supine anteroposterior chest radiograph (CXR) was taken from each model
      and interpreted by a senior radiologist, and the image results were compared to
      CT. RESULTS: All 20 hemithoraces with PTX were correctly identified by CT, while
      six remained occult after interpreting the CXRs. The PTXs were anterior (100%),
      lateral (95%), medial (80%), basal (60%), apical (45%), and posterior (15%). The
      major proportion of the insufflated 500-mL volume was found in the anterior,
      medial, and basal recesses. CONCLUSIONS: The authors found the distribution of
      the intrathoracic air to be similar between a porcine model and that to be
      expected in human trauma patients, all having predominantly anterior PTX
      topographies. In a training facility, the model is easy to set up and can be
      scanned by the participants multiple times. To acquire the necessary skills to
      perform thoracic US examinations for PTX, the porcine models could be useful.

PMID- 22594365
TI  - Building a better mousetrap for chest pain.

PMID- 22594366
TI  - Medical malpractice in Taiwan: injury types, compensation, and specialty risk.
AB  - The authors analyzed all medical malpractice claims from 2000 to 2008 using cases
      from the national database of the judicial system of Taiwan. The objective was to
      describe the factors associated with malpractice claims in Taiwan, a non-Western
      country that does not have a common law heritage. Emergency physicians (EPs) were
      the most likely to be sued and made the highest median payments. Most lawsuits
      involved death or permanent injury. Eighty-two percent of the cases were settled
      in the physician's favor.

PMID- 22594369
TI  - Improving teamwork and communication in trauma care through in situ simulations.
AB  - OBJECTIVES: Teamwork and communication often play a role in adverse clinical
      events. Due to the multidisciplinary and time-sensitive nature of trauma care,
      the effects of teamwork and communication can be especially pronounced in the
      treatment of the acutely injured patient. Our hypothesis was that an in situ
      trauma simulation (ISTS) program (simulating traumas in the trauma bay with all
      members of the trauma team) could be implemented in an emergency department (ED)
      and that this would improve teamwork and communication measured in the clinical
      setting. METHODS: This was an observational study of the effect of an ISTS
      program on teamwork and communication during trauma care. The authors observed a
      convenience sample of 39 trauma activations. Cases were selected by their
      presenting to the resuscitation bay of a Level I trauma center between 09:00 and
      16:00, Monday through Thursday, during the study period. Teamwork and
      communication were measured using the previously validated Clinical Teamwork
      Scale (CTS). The observers were three Trauma Nursing Core Course certified RNs
      trained on the CTS by observing simulated and actual trauma cases and following
      each of these cases with a discussion of appropriate CTS scores with two
      certified Advanced Trauma Life Support instructors/emergency physicians. Cases
      observed for measurement were scored in four phases: 1) preintervention phase
      (baseline); 2) didactic-only intervention, the phase following a lecture series
      on teamwork and communication in trauma care; 3) ISTS phase, real trauma cases
      scored during period when weekly ISTSs were performed; and 4) potential decay
      phase, observations following the discontinuation of the ISTSs. Multirater
      agreement was assessed with Krippendorf's alpha coefficient; agreement was
      excellent (mean agreement = 0.92). Nonparametric procedures (Kruskal-Wallis) were
      used to test the hypothesis that the scores observed during the various phases
      were different and to compare each individual phase to baseline scores. RESULTS:
      The ISTS program was implemented and achieved regular participation of all
      components of our trauma team. Data were collected on 39 cases. The scores for 11
      of 14 measures improved from the baseline to the didactic phase, and the mean and
      median scores of all CTS component measures were greatest during the ISTS phase.
      When each phase was compared to baseline scores, using the baseline as a control,
      there were no significant differences seen during the didactic or the decay
      phases, but 12 of the 14 measures showed significant improvements from the
      baseline to the simulation phase. However, when the Kruskal-Wallis test was used
      to test for differences across all phases, only overall communication showed a
      significant difference. During the potential decay phase, the scores for every
      measure returned to baseline phase values. CONCLUSIONS: This study shows that an
      ISTS program can be implemented with participation from all members of a
      multidisciplinary trauma team in the ED of a Level I trauma center. While
      teamwork and communication in the clinical setting were improved during the ISTS
      program, this effect was not sustained after ISTS were stopped.

PMID- 22594368
TI  - Racial disparities in testing for sexually transmitted infections in the
      emergency department.
AB  - OBJECTIVES: The objective of this study was to determine predictors of sexually
      transmitted infection (STI) testing among adolescent females presenting to an
      urban pediatric emergency department (ED) with symptoms potentially suggestive of
      an STI. METHODS: This was a secondary analysis of data collected in a prospective
      prevalence study of STIs among a consecutive sample of symptomatic females aged
      14 to 19 years presenting to a pediatric ED with lower abdominal or genitourinary
      complaints. The outcome of interest was performance of an STI test. Correlates of
      interest included patient age, race, insurance status, chief complaint, presence
      of comorbid conditions, and treating physician sex. RESULTS: Of the 328
      adolescent females who presented to the ED with STI-related complaints and met
      inclusion criteria, 15.6% did not undergo STI testing. Univariable analysis
      revealed that black or African American race (odds ratio [OR] = 4.98, 95%
      confidence interval [CI] = 2.67 to 9.30) and nonprivate insurance (OR = 3.47; 95%
      CI = 1.83 to 6.58) were significantly associated with the performance of STI
      testing. In a multivariable model, only black or African American race (OR =
      3.94; 95% CI = 1.96 to 7.91) remained significantly associated with the
      performance of STI testing. CONCLUSIONS: A substantial number of adolescent
      females who presented with complaints suggestive of an STI did not undergo STI
      testing, and a racial disparity in STI testing was noted. The racial disparity in
      rates of STI testing among symptomatic adolescent girls presenting to the ED
      warrants further study to confirm validity, to determine if disparity reflects
      physicians' biases, and to inform strategies for controlling the present epidemic
      of STIs in adolescents.

PMID- 22594371
TI  - Brain death determination in Israel: the first two years experience following
      changes to the brain death law-opportunities and challenges.
AB  - To increase support for the concept of brain death, changes accommodating
      requirements of the religious authorities were made to the Brain Death Act in
      Israel. These included (1) considering patient wishes regarding brain death
      determination (BDD); (2) mandatory performance of apnea and ancillary testing;
      (3) establishment of an accreditation committee and (4) requirement for physician
      training courses. We describe the first 2 years experience following
      implementation (2010-2011). During 2010, the number of BDD decreased from
      21.9/million population (during the years 2007-2009) to 16.0 (p < 0.001). Reasons
      included family resistance to brain death testing (27 cases), inability to
      perform apnea testing (7) and logistic problems related to ancillary testing (26
      cases). The number of physicians available to declare brain death also decreased
      (210 vs. 102). During 2011, BDDs increased to 20.5/million following the
      introduction of radionuclide angiography as an ancillary test; other reasons for
      nondetermination persisted (family resistance 26 cases, inability to perform
      apnea testing 10 cases). Instead of increasing opportunities, many obstacles were
      encountered following the changes to the Brain Death Act. Although some of these
      challenges have been met, longer term follow-up is required to assess their
      complete impact.

PMID- 22594372
TI  - Identification of stable endogenous control genes for transcriptional profiling
      of photon, proton and carbon-ion irradiated cells.
AB  - BACKGROUND: Quantitative analysis of transcriptional regulation of genes is a
      prerequisite for a better understanding of the molecular mechanisms of action of
      different radiation qualities such as photon, proton or carbon ion irradiation.
      Microarrays and real-time quantitative RT-PCR (qRT-PCR) are considered the two
      cornerstones of gene expression analysis. In interpreting these results it is
      critical to normalize the expression levels of the target genes by that of
      appropriately selected endogenous control genes (ECGs) or housekeeping genes. We
      sought to systematically investigate common ECG candidates for their stability
      after different radiation modalities in different human cell lines by qRT-PCR. We
      aimed to identify the most robust set of ECGs or housekeeping genes for
      transcriptional analysis in irradiation studies. METHODS: We tested the
      expression stability of 32 ECGs in three human cancer cell lines. The epidermoid
      carcinoma cells (A431), the non small cell lung carcinoma cells (A549) and the
      pancreatic adenocarincoma cells (BxPC3) were irradiated with photon, proton and
      carbon ions. Expression Heat maps, clustering and statistic algorithms were
      employed using SUMO software package. The expression stability was evaluated by
      computing: mean, standard deviation, ANOVA, coefficient of variation and the
      stability measure (M) given by the geNorm algorithm. RESULTS: Expression analysis
      revealed significant cell type specific regulation of 18 out of 32 ECGs (p <
      0.05). A549 and A431 cells shared a similar pattern of ECG expression as the
      function of different radiation qualities as compared to BxPC3. Of note, the
      ribosomal protein 18S, one of the most frequently used ECG, was differentially
      regulated as the function of different radiation qualities (p <= 0.01). A
      comprehensive search for the most stable ECGs using the geNorm algorithm
      identified 3 ECGs for A431 and BxPC3 to be sufficient for normalization. In
      contrast, 6 ECGs were required to properly normalize expression data in the more
      variable A549 cells. Considering both variables tested, i.e. cell type and
      radiation qualities, 5 genes-- RPLP0, UBC, PPIA, TBP and PSMC4-- were identified
      as the consensus set of stable ECGs. CONCLUSIONS: Caution is warranted when
      selecting the internal control gene for the qRT-PCR gene expression studies.
      Here, we provide a template of stable ECGs for investigation of radiation induced
      gene expression.

PMID- 22594373
TI  - Clinical outcomes of a new self-help booklet for premature ejaculation.
AB  - INTRODUCTION: Premature ejaculation (PE) is quite common. Although effective
      treatments do exist, only a few affected people consult a practitioner in order
      to overcome their problem. At the same time, studies have shown that reading
      didactical documents about their PE problem (bibliotherapy) can be useful to men.
      AIM: The aim of this study was to improve the bibliotherapy approach using up-to
      date knowledge and techniques. The expected benefits were the following: (i) an
      effective manual shorter than previous ones; (ii) easier to assimilate
      therapeutic principles; and (iii) a method thereby made accessible to a broad
      population most of whom usually do not consult for this type of sexual problem.
      METHOD: A short bibliotherapy titled The Practical Guide of PE[in French] was
      tested among PE subjects who were diagnosed with PE according to Diagnostic and
      Statistical Manual of Mental Disorders, fourth edition, text revision criteria.
      Assessments were made at baseline (N = 421), at 4-8 months (N = 120), and at 10
      14 months (N = 79) after they read The Practical Guide. A control group of 66
      subjects was left on a waiting list and was assessed 2 months after baseline.
      MAIN OUTCOME MEASURES: The main outcome measures are self-reported ejaculatory
      latency time, feeling of control upon ejaculation, sexual satisfaction, distress
      related to PE, anxiety experienced during sexual intercourse, and sexual
      cognitions (Sexual Irrationality Questionnaire). RESULTS: Significant
      improvements were found for all the self-reported parameters, both at 4-8 and at
      10-14 months after the bibliotherapy. The improvements were associated with an
      adjustment of sexual cognitions. The response to treatment seemed better for
      those subjects with moderate PE. Although the severity criteria used in this
      study did not precisely meet the International Society for Sexual Medicine
      criteria for lifelong PE, they were likely related. The response did not seem to
      be affected by variables such as age, education, or personality. CONCLUSION: Its
      cost/benefit ratio makes The Practical Guide a valuable therapeutic tool.

PMID- 22594374
TI  - Toll-like receptor 9 (TLR9) polymorphism associated with symptomatic malaria: a
      cohort study.
AB  - BACKGROUND: In areas mesoendemic for malaria transmission, symptomatic
      individuals play a significant role as reservoirs for malaria infection.
      Understanding the pathogenesis of symptomatic malaria is important in devising
      tools for augmenting malaria control. In this study, the effect of TLR9
      polymorphisms on susceptibility to symptomatic malaria was investigated among
      Ghanaian children. METHODS: Four hundred and twenty nine (429) healthy Ghanaian
      children, aged three to eleven years (3-11 years), were enrolled into a cohort
      study and actively followed up for symptomatic malaria for one year. Four TLR9
      single nucleotide polymorphisms (SNPs) namely: rs187084 (C-1486 T), rs5743836(C
      1237 T), rs352139 (G + 1174A) and rs352140 (G + 2848A) were genotyped by direct
      sequencing, and their attributable and relative risks for symptomatic malaria
      determined. TLR9 haplotypes were inferred using the PHASE software and analysed
      for the risk of symptomatic malaria. A luciferase assay was performed to
      investigate whether the TLR9 haplotypes influence TLR9 promoter activity.
      RESULTS: The rs352139 GG genotype showed a significantly increased relative risk
      of 4.8 for symptomatic malaria (P = 0.0024) and a higher mean parasitaemia (P =
      0.04). Conversely, the rs352140 GG genotype showed a significantly reduced
      relative risk of 0.34 (P = 0.048). TLR9 haplotypes analyses showed that TTAG
      haplotype was significantly associated with reduced relative risk of 0.2 for
      symptomatic malaria (P = 4*10-6) and a lower mean parasitaemia (0.007), while
      CTGA haplotype had an increased relative risk of 3.3 (P = 0.005). Functional
      luciferase reporter gene expression assay revealed that the TTA haplotype had a
      significantly higher promoter activity than the CCG, CTG and TCG haplotypes.
      CONCLUSIONS: Taken together, these findings indicate a significant association of
      TLR9 gene polymorphisms with symptomatic malaria among Ghanaian children in
      Dangme-West district.

PMID- 22594375
TI  - Therapeutic effects of metabotropic glutamate receptor 5 positive allosteric
      modulator CDPPB on phencyclidine-induced cognitive deficits in mice.
AB  - This study was undertaken to examine the effects of CDPPB (3-cyano-N-(1,3
      diphenyl-1H-pyrazol-5-yl)benzamide), a positive allosteric modulator (PAM) of
      metabotropic glutamate receptor 5 (mGlu5), on cognitive deficits in mice after
      repeated administration of the N-methyl-D-aspartate (NMDA) receptor antagonist
      phencyclidine (PCP). In the novel object recognition test, PCP (10 mg/kg/day for
      10 days)-induced cognitive deficits in mice were not improved by a single
      administration of CDPPB (10 mg/kg/day). However, PCP (10 mg/kg/day for 10 days)
      induced cognitive deficits in mice were significantly improved by subsequent
      subchronic (14 days) administration of CDPPB (10 mg/kg/day), but not of CDPPB
      (1.0 mg/kg/day). This study suggests that PCP-induced cognitive deficits in mice
      are improved by subsequent subchronic administration of CDPPB. Therefore, mGlu5
      PAMs would be potential therapeutic drugs for cognitive deficits in
      schizophrenia.

PMID- 22594376
TI  - Glioneuronal tumor with neuropil-like islands: clinical, morphologic,
      immunohistochemical, and molecular features of three pediatric cases.
AB  - Glioneuronal tumors with neuropil-like islands are rare. The 1st reported cases
      were localized in the cerebral hemispheres of adults, showed homogeneous
      histopathologic features (infiltrating astrocytic growth and neuropil-like
      islands rimmed by neuronal cells), and had an unfavorable behavior. We report 3
      pediatric cases (1 boy and 2 girls, ages 4, 6, and 8 years, respectively). The
      boy had a cerebral tumor, and the girls had a spinal tumor. The younger girl also
      had multiple posterior fossa lesions. The boy and older girl underwent a gross
      total resection. The younger girl underwent a subtotal resection of the spinal
      tumor; posterior fossa lesions were not surgically treated. The boy and younger
      girl are in complete remission at 33 and 24 months, respectively, after surgery
      and subsequent high-dose chemoradiotherapy. The older girl had a recurrence that
      was partially resected. Afterward, she started high-dose chemoradiotherapy and
      had an optimal radiologic response at 4 months follow up. Microscopically, the
      common denominator was the presence of synaptophysin-positive neuropil-like
      islands. One tumor showed ependymal features (pseudorosettes and punctate
      epithelial membrane antigen immunopositivity). Two tumors had 1p deletion. 19q
      deletion, MGMT gene promoter methylation, EGFR amplifications or polysomy, and
      EGFR, IDH1, IDH2, and TP53 genes mutation analyses yielded negative results. In
      conclusion, glioneuronal tumor with neuropil-like islands can affect children,
      arise in the spinal cord, and show ependymal features in its glial component. A
      high-dose chemoradiotherapy program is effective.

PMID- 22594377
TI  - Impact of pediatric epilepsy on sleep patterns and behaviors in children and
      parents.
AB  - PURPOSE: Disrupted sleep patterns in children with epilepsy and their parents are
      commonly described clinically. A number of studies have shown increased frequency
      of sleep disorders among pediatric epilepsy patients; however, few have
      characterized the association between epilepsy and parental sleep quality and
      household sleeping arrangements. The purpose of this study was to explore the
      effect of pediatric epilepsy on child sleep, parental sleep and fatigue, and
      parent-child sleeping arrangements, including room sharing and cosleeping.
      METHODS: Parents of children 2 to 10 years of age with and without epilepsy
      completed written questionnaires assessing seizure history, child and parent
      sleep, and household sleeping arrangements. Children's Sleep Habits Questionnaire
      (CSHQ) scores were used to evaluate sleep disturbances for the child. The
      Pittsburgh Sleep Quality Index (PSQI) and the Iowa Fatigue Scale (IFS) were used
      to evaluate parental sleep and fatigue, respectively. The Early Childhood
      Epilepsy Severity Scale (E-Chess) was used to assess epilepsy severity. KEY
      FINDINGS: One hundred five households with a child with epilepsy and 79 controls
      participated in this study. Households with a child with epilepsy reported
      increased rates of both parent-child room sharing (p < 0.001) and cosleeping (p =
      0.005) compared to controls. Children with epilepsy were found to have greater
      sleep disturbance by total CSHQ score (p < 0.001) and the following subscores:
      parasomnias (p < 0.001), night wakings (p < 0.001), sleep duration (p < 0.001),
      daytime sleepiness (<0.001), sleep onset delay (p = 0.009), and bedtime
      resistance (p = 0.023). Parents of children with epilepsy had increased sleep
      dysfunction (p = 0.005) and were more fatigued (p < 0.001). Severity of epilepsy
      correlated positively with degree of child sleep dysfunction (0.192, p = 0.049),
      parental sleep dysfunction (0.273, p = 0.005), and parental fatigue (0.324, p =
      0.001). Antiepileptic drug polytherapy was predictive of greater childhood sleep
      disturbances. Nocturnal seizures were associated with parental sleep problems,
      whereas room sharing and cosleeping behavior were associated with child sleep
      problems. Within the epilepsy cohort, 69% of parents felt concerned about night
      seizures and 44% reported feeling rested rarely or never. Finally, 62% of parents
      described decreased sleep quality and/or quantity with cosleeping. SIGNIFICANCE:
      Pediatric epilepsy can significantly affect sleep patterns for both the affected
      child and his or her parents. Parents frequently room share or cosleep with their
      child, adaptations which may have detrimental effects for many households.
      Clinicians must not only be attentive to the sleep issues occurring in pediatric
      patients with epilepsy, but also for the household as a whole. These data provide
      evidence of a profound clinical need for improved epilepsy therapeutics and the
      development of nocturnal seizure monitoring technologies.

PMID- 22594379
TI  - What's going on with these lithium reagents?
AB  - This Perspective describes a series of research projects that led the author from
      an interest in lithium reagents as synthetically valuable building blocks to
      studies aimed at understanding the science behind the empirical art developed by
      synthetic chemists trying to impose their will on these reactive species.
      Understanding lithium reagent behavior is not an easy task; since many are
      mixtures of aggregates, various solvates are present, and frequently new mixed
      aggregates are formed during their reactions with electrophiles. All of these
      species are typically in fast exchange at temperatures above -78  degrees C.
      Described are multinuclear NMR experiments at very low temperatures aimed at
      defining solution structures and dynamics and some kinetic studies, both using
      classic techniques as well as the rapid inject NMR (RINMR) technique, which can
      in favorable cases operate on multispecies solutions without the masking effect
      of the Curtin-Hammett principle.

PMID- 22594378
TI  - Comparison of low and high dose ionising radiation using topological analysis of
      gene coexpression networks.
AB  - BACKGROUND: The growing use of imaging procedures in medicine has raised concerns
      about exposure to low-dose ionising radiation (LDIR). While the disastrous
      effects of high dose ionising radiation (HDIR) is well documented, the
      detrimental effects of LDIR is not well understood and has been a topic of much
      debate. Since little is known about the effects of LDIR, various kinds of wet-lab
      and computational analyses are required to advance knowledge in this domain. In
      this paper we carry out an "upside-down pyramid" form of systems biology analysis
      of microarray data. We characterised the global genomic response following 10 cGy
      (low dose) and 100 cGy (high dose) doses of X-ray ionising radiation at four time
      points by analysing the topology of gene coexpression networks. This study
      includes a rich experimental design and state-of-the-art computational systems
      biology methods of analysis to study the differences in the transcriptional
      response of skin cells exposed to low and high doses of radiation. RESULTS: Using
      this method we found important genes that have been linked to immune response,
      cell survival and apoptosis. Furthermore, we also were able to identify genes
      such as BRCA1, ABCA1, TNFRSF1B, MLLT11 that have been associated with various
      types of cancers. We were also able to detect many genes known to be associated
      with various medical conditions. CONCLUSIONS: Our method of applying network
      topological differences can aid in identifying the differences among similar (eg:
      radiation effect) yet very different biological conditions (eg: different dose
      and time) to generate testable hypotheses. This is the first study where a
      network level analysis was performed across two different radiation doses at
      various time points, thereby illustrating changes in the cellular response over
      time.

PMID- 22594380
TI  - Energetic basis of human telomeric DNA folding into G-quadruplex structures.
AB  - Recent theoretical studies performed on the folding/unfolding mechanism of the
      model telomeric human DNA, 5'-AGGGTTAGGGTTAGGGTTAGGG-3' (Tel22), have indicated
      that in the presence of K(+) ions Tel22 folds into two hybrid G-quadruplex
      structures characterized by one double and two reversal TTA loops arranged in a
      different way. They predicted a new unfolding pathway from the initial mixture of
      hybrid G-quadruplexes via the corresponding intermediate triplex structures into
      the final, fully unfolded state. Significantly, no experimental evidence
      supporting the suggested pathway has been reported. In the current work, we
      performed a comprehensive global thermodynamic analysis of calorimetric (DSC,
      ITC) and spectroscopic (CD) data obtained on monitoring the folding/unfolding of
      Tel22 induced by changes of temperature and K(+) concentration. We show that
      unfolding of Tel22 may be described as a monomolecular equilibrium three-state
      process that involves thermodynamically distinguishable folded (F), intermediate
      (I), and unfolded (U) state. Considering that calorimetric methods cannot
      distinguish between energetically similar G-quadruplex or triplex conformations
      predicted by the theoretical model one can conclude that our results represent
      the first experimental support of the suggested unfolding/folding mechanism of
      Tel22. This conclusion is confirmed by the fact that the estimated number of K(+)
      ions released upon each unfolding step in our thermodynamic model agrees well
      with the corresponding values predicted by the theoretical model and that the
      observed changes in enthalpy, entropy, and heat capacity accompanying the F -> I
      and I -> U transitions can be reasonably explained only if the intermediate state
      I is considered to be a triplex structural conformation.

PMID- 22594381
TI  - Api88 is a novel antibacterial designer peptide to treat systemic infections with
      multidrug-resistant Gram-negative pathogens.
AB  - The emergence of multiple-drug-resistant (MDR) bacterial pathogens in hospitals
      (nosocomial infections) presents a global threat of growing importance,
      especially for Gram-negative bacteria with extended spectrum beta-lactamase
      (ESBL) or the novel New Delhi metallo-beta-lactamase 1 (NDM-1) resistance.
      Starting from the antibacterial peptide apidaecin 1b, we have optimized the
      sequence to treat systemic infections with the most threatening human pathogens,
      such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and
      Acinetobacter baumannii. The lead compound Api88 enters bacteria without lytic
      effects at the membrane and inhibits chaperone DnaK at the substrate binding
      domain with a K(D) of 5 MUmol/L. The Api88-DnaK crystal structure revealed that
      Api88 binds with a seven residue long sequence (PVYIPRP), in two different modes.
      Mice did not show any sign of toxicity when Api88 was injected four times
      intraperitoneally at a dose of 40 mg/kg body weight (BW) within 24 h, whereas
      three injections of 1.25 mg/kg BW and 5 mg/kg BW were sufficient to rescue all
      animals in lethal sepsis models using pathogenic E. coli strains ATCC 25922 and
      Neumann, respectively. Radioactive labeling showed that Api88 enters all organs
      investigated including the brain and is cleared through both the liver and
      kidneys at similar rates. In conclusion, Api88 is a novel, highly promising, 18
      residue peptide lead compound with favorable in vitro and in vivo properties
      including a promising safety margin.

PMID- 22594382
TI  - Role of the Hofmeister series in the formation of ionic-liquid-based aqueous
      biphasic systems.
AB  - Among the numerous and interesting features of ionic liquids is their ability to
      form aqueous biphasic systems (ABSs) when combined with inorganic or organic
      salts in aqueous media. In this work, a wide range of salts was studied, aiming
      at gathering a detailed picture on the molecular mechanisms that govern the
      ability of the salt ions to induce the formation of ionic-liquid-based ABSs. For
      that purpose, 1-butyl-3-methylimidazolium trifluoromethanesulfonate was chosen
      due to its facility to undergo liquid-liquid demixing in aqueous media containing
      conventional salts. The corresponding ternary phase diagrams, tie-lines, and tie
      line lengths were determined at 298 K and atmospheric pressure. With the large
      body of data measured in this work, it was possible to establish a scale on the
      salt cation and anion abilities to induce the formation of ionic-liquid-based
      ABSs, which follows the Hofmeister series, and to show that the molar entropy of
      hydration of the salt ions is the driving force for aqueous two-phase system
      formation.

PMID- 22594383
TI  - The effects of cognitive speed of processing training among older adults with
      psychometrically- defined mild cognitive impairment.
AB  - Despite the growing interest in cognitive training programs as a potential non
      pharmacological approach to slowing cognitive decline in mild cognitive
      impairment (MCI), there has been little research on the differential
      effectiveness of training among subtypes of MCI (i.e., amnestic, single non
      amnestic, and multi-domain). The current study examined the longitudinal effects
      of cognitive speed of processing training (SOPT) among older adults with
      psychometricallydefined MCI from the Advanced Cognitive Training for Independent
      and Vital Elderly (ACTIVE) trial. Mixed model ANOVAs examined the effectiveness
      of SOPT in participants with MCI relative to controls and also compared training
      effectiveness in MCI subgroups to appropriate controls. A mixed effects model
      compared SOPT training effects longitudinally across five years relative to
      controls. A second mixed effects model compared the durability of training gains
      between the MCI subtypes across 5 years. All subtypes of MCI showed immediate
      improvement post-training relative to controls, with the single non-amnestic
      subtype showing the most benefit. Additionally, all subtypes showed similar
      trajectories across five years. There were no significant changes in performance
      across time, indicating initial training gains were maintained. These results
      provide support for the effectiveness and potential durability of SOPT among
      persons with MCI regardless of subtype. Future research should investigate if
      SOPT transfers to improvements in the everyday functioning of those with MCI.

PMID- 22594384
TI  - Editorial: Research ideas and academic integrity: consideration of some key
      issues.

PMID- 22594385
TI  - Differences between community professional and patient perceptions of chronic
      obstructive pulmonary disease treatment outcomes: a qualitative study.
AB  - AIMS AND OBJECTIVES: This study aims to define, compare and order 'assessed needs
      and defined outcomes' of professional providers of chronic obstructive pulmonary
      disease services with patients' 'prioritised needs and defined outcomes' and
      relate these to service provision. BACKGROUND: Long-term morbidity and death
      rates from respiratory diseases in the UK are increasing. Few studies report
      patient views and perceptions of needs or priorities for respiratory conditions
      in primary care. None compare patient's and health professional's perceptions of
      patient needs, which may identify specific changes for service delivery. DESIGN:
      A qualitative study using focus group discussion and nominal group technique to
      define, compare and order professional's and patient's groups' statements to
      prioritise perceptions. METHOD: Specialist professionals and patients with
      chronic obstructive pulmonary disease were recruited to focus groups using
      systematic purposive sampling. Nominal group ordering of agreed statements
      occurred after the discussions followed by presentation of results to groups for
      validation. RESULTS: Four key perceptions ordered and compared show both
      professionals and patients agreed that access to equitably provided services
      included more respiratory rehabilitation; other priorities indicate key
      differences between professional's and patient's perceptions of financial
      support, the communication of health education and the need for better provision
      of palliative care at end of life. CONCLUSIONS: The study offers new knowledge
      about what patients in all stages of the disease process consider important for
      services that will retain their independence. This qualitative study illuminates
      and compares professional's and patient's priorities for service delivery and
      their perceptions of chronic obstructive pulmonary disease services. RELEVANCE TO
      CLINICAL PRACTICE: Changing respiratory services to support patient's perceived
      needs enhances their independence.

PMID- 22594386
TI  - The effect of bitter almond oil and massaging on striae gravidarum in
      primiparaous women.
AB  - AIM: This study aims to identify the effect of applying bitter almond oil with
      and without massage on preventing striae gravidarum during pregnancy. BACKGROUND:
      Striae gravidarum is a dermatological problem bringing about cosmetic concerns in
      about 90% of pregnant women. On the onset, striae gravidarum appears as a pink
      purple atrophic strip. Striae appear pale atrophic in the postnatal period, but
      they never disappear completely. DESIGN: In view of the physiology of striae
      gravidarum formation, this study employs a posttest-only quasi-experimental
      design with a control group. METHODS: The participants of this study were the
      primiparous women who visited the pregnancy unit of a medical centre in the
      eastern region of Turkey between February 1st, 2010 and April 15th, 2011. The
      participants were divided into three groups: the primiparous women who applied
      bitter almond oil with massage (n = 47), who merely applied bitter almond oil (n
      = 48) and who were in the control group (n = 46). RESULTS: The frequency of
      striae gravidarum was 20% among the women who applied bitter almond oil with
      massage, 38.8% among those who merely applied almond oil and 41.2% in the control
      group. A statistically significant difference was observed in the frequency of
      striae gravidarum between the groups, and it was the group who applied almond oil
      with massage that accounted for the difference (p < 0.001). The frequency of
      striae gravidarum was also found to be lower in the group who applied almond oil
      with massage compared to the others (p < 0.05). CONCLUSION: It was found that a
      15-minute massage applied with almond oil during pregnancy reduced the
      development of striae gravidarum, but using bitter almond oil had no effect on
      this in itself. It is recommended that pregnant women be informed about the
      positive effects of massaging applied with almond oil early during their
      pregnancy. RELEVANCE TO CLINICAL PRACTICE: Nurses and midwives can use the
      findings of this study in preventing the development of striae gravidarum during
      pregnancy.

PMID- 22594387
TI  - Stressors and coping mechanisms in live-related renal transplantation.
AB  - AIM: To explore donor and recipient experiences of stressors and coping
      mechanisms associated with live-related renal transplantation. BACKGROUND: Live
      related renal transplantation is an effective and efficient treatment for end
      stage kidney disease, but is also associated with a variety of stressors. DESIGN:
      Longitudinal, phenomenological study. METHODS: Eleven live kidney donors and
      their recipients (n = 22) were recruited from a regional renal transplant centre
      in South-West England. Data were collected through three recorded, semi
      structured interviews, conducted pretransplant and at three and 10 months post
      transplant. Interviews were transcribed verbatim, analysed using a process of
      thematic analysis and validated through a constructive process of inter-rater
      reliability. RESULTS: End-stage kidney disease, dialysis and live transplantation
      produced a variety of stressors for donors and recipients. Common stressors
      included the live transplantation decision-making process, the prospect of
      surgery and postoperative recovery, follow-up care for donors and, in particular,
      concern for each other, especially amongst recipients. The main stressor,
      however, was fear of transplant failure. Participants used a variety of problem-
      and emotion-focused coping mechanisms to deal with these stressors and donors and
      recipients actively supported each other through the transplantation process.
      CONCLUSION: Renal transplantation remains the treatment of choice for most
      patients with end-stage kidney disease but is a source of considerable stress for
      donors and especially recipients and subsequently requires a range of coping
      mechanisms, including social support. RELEVANCE TO CLINICAL PRACTICE: Patients
      need to be adequately informed of the risks associated with transplantation and
      provided with appropriate emotional care and support throughout the
      transplantation process. Health professionals also need to be mindful of
      assessing the needs and managing realistic expectations of patients and their
      families.

PMID- 22594388
TI  - Treatment and ergonomics training of work-related lower back pain and body
      posture problems for nurses.
AB  - AIMS: The purpose of the study was to measure the effectiveness of a spine
      training programme (Back School) in nurses who have been living with chronic low
      back pain. It was hypothesised that active therapy, ergonomics and education
      called Back School will significantly decrease the pain intensity levels and
      improve the body posture of the study participants. BACKGROUND: A chronic low
      back pain is a significant work-related health problem among healthcare workers
      around the world. Proper body posture is essential for decreasing pain in
      healthcare workers who have history of chronic low back pain. By teaching proper
      body posture and with the creation of occupational settings that are 'spine
      friendly' hospitals and other healthcare settings can significantly lower the
      suffering of their nursing staff. DESIGN: Single-blinded randomised controlled
      trial was utilised with six- and 12-months follow-up. METHODS: The study was
      carried out at the University of Pecs, Faculty of Health Sciences from 2007 to
      2008 involving 124 nurses with low back pain. Participants were randomly assigned
      to the study group (who have received ergonomics training and education called
      Back School) with an intervention conducted once a week for a six-week period.
      The control group received passive physiotherapy once a week for a six-week
      period. Further follow-up measurements were conducted at six and 12 months,
      respectively. The study variables and outcome measures were pain intensity and
      body posture (angle of thoracic kyphosis and lumbar lordosis). The pain intensity
      was investigated with the Visual Analogue Scale. Body posture was recorded and
      analysed with the Zebris biomechanical motion analysis system. RESULTS: The
      statistical analysis of repeated measures indicated a significant decrease in
      back pain intensity after the therapy in both groups, compared with measurements
      before the therapy; however, the BS group showed significantly better results
      during the six-month and one-year follow-up period. The biomechanical analysis of
      postures after the therapy in the BS group showed significant improvements over
      the control group; during the follow-up, the difference was still significant,
      yet slightly reduced. CONCLUSIONS: This study has shown that a significant
      reduction in the pain intensity and improvement in body posture can be achieved
      by the usage of the active physical therapy methods (Back School) in nurses who
      are experiencing chronic lower back pain. RELEVANCE TO CLINICAL PRACTICE: The
      Back School programme when compared with the passive physical therapies (such as
      massage, ultrasound treatment, etc.) shows significant improvement in reduction
      in pain and greatly improves the posture of healthcare workers. The adoption of
      the Back School programme for the treatment of the healthcare workers with
      chronic low back problems should be a treatment of choice and standard that
      should be adopted when designing occupational healthcare policies and procedures.

PMID- 22594389
TI  - Validating the 'clinical learning environment, supervision and nurse teacher'
      CLES+T instrument in primary healthcare settings using confirmatory factor
      analysis.

PMID- 22594390
TI  - Development and implementation of an observational pain assessment protocol in a
      nursing home.

PMID- 22594391
TI  - Commentary on Haws J, Ramjeet J & Gray R (2011) A national survey of GP and nurse
      attitudes and beliefs towards depression after myocardial infarction. Journal of
      Clinical Nursing 20, 3215-3223.

PMID- 22594392
TI  - A dietary resveratrol-rich grape extract prevents the developing of
      atherosclerotic lesions in the aorta of pigs fed an atherogenic diet.
AB  - The presence of grape and wine polyphenol resveratrol (RES) in the diet is
      negligible. Therefore, the cardiovascular benefits of this molecule, in a dietary
      context, remain to be established. We aimed to investigate, through dietary
      intervention, the effects of a resveratrol-rich grape extract (GE-RES) on the
      prevention of early aortic lesions in pigs fed an atherogenic diet (AD). These
      effects were compared with those produced by a grape extract lacking RES (GE) or
      RES alone. Pigs fed the AD for 4 months showed early atherosclerotic lesions in
      the thoracic aorta: degeneration and fragmentation of elastic fibers, increase of
      intima thickness, subendothelial fibrosis, and accumulation of fatty cells and
      anion superoxide radicals. GE-RES was the most effective treatment and prevented
      the disruption of aortic elastic fibers, decreased their alteration (57%), and
      reduced the intima thickness (33%) and the accumulation of fatty cells (42%) and
      O(2)(*-) (38%) in aortic tissue. In addition, GE-RES moderately downregulated the
      expression of the suppressors of cytokine signaling 1 (SOCS1) and 3 (SOCS3), key
      regulators of vascular cell responses, in peripheral mononuclear blood cells. Our
      results suggest that the consumption of this GE-RES nutraceutical, in a dietary
      prevention context, could prevent early atherosclerotic events. The presence of
      RES in the grape extract strengthened these effects.

PMID- 22594393
TI  - Chiral electromagnetic fields generated by arrays of nanoslits.
AB  - Using a modal matching theory, we demonstrate the generation of short-range,
      chiral electromagnetic fields via the excitation of arrays of staggered nanoslits
      that are chiral in two dimensions. The electromagnetic near fields, which exhibit
      a chiral density greater than that of circularly polarized light, can enhance the
      chiroptical interactions in the vicinity of the nanoslits. We discuss the
      features of nanostructure symmetry required to obtain the chiral fields and
      explicitly show how these structures can give rise to detection and
      characterization of materials with chiral symmetry.

PMID- 22594394
TI  - Sulphide production and corrosion in seawaters during exposure to FAME diesel.
AB  - Experiments were designed to evaluate the corrosion-related consequences of
      storing/transporting fatty acid methyl ester (FAME) alternative diesel fuel in
      contact with natural seawater. Coastal Key West, FL (KW), and Persian Gulf (PG)
      seawaters, representing an oligotrophic and a more organic- and inorganic mineral
      rich environment, respectively, were used in 60 day incubations with unprotected
      carbon steel. The original microflora of the two seawaters were similar with
      respect to major taxonomic groups but with markedly different species. After
      exposure to FAME diesel, the microflora of the waters changed substantially, with
      Clostridiales (Firmicutes) becoming dominant in both. Despite low numbers of
      sulphate-reducing bacteria in the original waters and after FAME diesel exposure,
      sulphide levels and corrosion increased markedly due to microbial sulphide
      production. Corrosion morphology was in the form of isolated pits surrounded by
      an intact, passive surface with the deepest pits associated with the
      fuel/seawater interface in the KW exposure. In the presence of FAME diesel, the
      highest corrosion rates measured by linear polarization occurred in the KW
      exposure correlating with significantly higher concentrations of sulphur and
      chlorine (presumed sulphide and chloride, respectively) in the corrosion
      products.

PMID- 22594395
TI  - Real-time investigation of the muco-adhesive properties of Lactococcus lactis
      using a quartz crystal microbalance with dissipation monitoring.
AB  - This work was devoted to probe, at the entire population level, interactions
      between mucins and Lactococcus lactis, using QCM-D. Real-time monitoring of
      adsorption on polystyrene of PGM (Pig Gastric Mucin) and subsequent adhesion of
      L. lactis was performed for IBB477 and MG1820 strains. Measuring simultaneously
      shifts in resonance frequency and dissipation on the polystyrene-coated crystal
      demonstrated a two-phase process for PGM adsorption. XPS analysis confirmed the
      presence of adsorbed mucin. The Voigt-based model was used to describe the QCM-D
      outputs. The predicted thickness of the PGM layer was consistent with the AFM
      experimental value. Adhesion of L. lactis to bare or PGM-coated polystyrene was
      then monitored, in combination with DAPI cell counting. Positive frequency shifts
      were caused by adhering bacteria. The presence of adsorbed PGM strongly reduced
      bacterial adhesion. However, adhesion of IBB477 to the PGM coating was greatly
      increased in comparison with that of MG1820. Muco-adhesion may be a highly
      variable and valuable phenotypic trait among L. lactis strains.

PMID- 22594396
TI  - Short-term effects of medetomidine on photosynthesis and protein synthesis in
      periphyton, epipsammon and plankton communities in relation to predicted
      environmental concentrations.
AB  - Medetomidine is a new antifouling substance, highly effective against barnacles.
      As part of a thorough ecotoxicological evaluation of medetomidine, its short-term
      effects on algal and bacterial communities were investigated and environmental
      concentrations were predicted with the MAMPEC model. Photosynthesis and bacterial
      protein synthesis for three marine communities, viz. periphyton, epipsammon and
      plankton were used as effect indicators, and compared with the predicted
      environmental concentrations (PECs). The plankton community showed a significant
      decrease in photosynthetic activity of 16% at 2 mg l-1 of medetomidine, which was
      the only significant effect observed. PECs were estimated for a harbor, shipping
      lane and marina environment using three different model scenarios (MAMPEC
      default, Baltic and OECD scenarios). The highest PEC of 57 ng l-1, generated for
      a marina with the Baltic scenario, was at least 10,000-fold lower than the
      concentration that significantly decreased photosynthetic activity. It is
      concluded that medetomidine does not cause any acute toxic effects on bacterial
      protein synthesis and only small acute effects on photosynthesis at high
      concentrations in marine microbial communities. It is also concluded that the
      hazard from medetomidine on these processes is low since the effect levels are
      much lower than the highest PEC.

PMID- 22594397
TI  - Conditioning of surfaces by macromolecules and its implication for the settlement
      of zoospores of the green alga Ulva linza.
AB  - Conditioning, ie the adsorption of proteins and other macromolecules, is the
      first process that occurs in the natural environment once a surface is immersed
      in seawater, but no information is available either regarding the conditioning of
      surfaces by artificial seawater or whether conditioning affects data obtained
      from laboratory assays. A range of self-assembled monolayers (SAMs) with
      different chemical terminations was used to investigate the time-dependent
      formation of conditioning layers in commercial and self-prepared artificial
      seawaters. Subsequently, these results were compared with conditioning by
      solutions in which zoospores of the green alga Ulva linza had been swimming.
      Spectral ellipsometry and contact angle measurements as well as infrared
      reflection absorption spectroscopy (IRRAS) were used to reveal the thickness and
      chemical composition of the conditioning layers. The extent that surface
      preconditioning affected the settlement of zoospores of U. linza was also
      investigated. The results showed that in standard spore settlement bioassays (45
      60 min), the influence of a molecular conditioning layer is likely to be small,
      although more substantial effects are possible at longer settlement times.

PMID- 22594398
TI  - Construction of 1,5-enynes by stereospecific Pd-catalyzed allyl-propargyl cross
      couplings.
AB  - The palladium-catalyzed cross-coupling of chiral propargyl acetates and allyl
      boronates delivers chiral 1,5-enynes with excellent levels of chirality transfer
      and can be applied across a broad range of substrates.

PMID- 22594399
TI  - Stereoselective synthesis of the monomeric unit of actin binding macrolide
      rhizopodin.
AB  - An efficient, scalable, and stereocontrolled synthesis of the entire carbon
      framework of an actin binding dimeric macrolide rhizopodin has been accomplished
      in its protected form. The key features of our synthesis include a titanium
      catalyzed anti acetal aldol reaction, a substrate controlled diastereoslelective
      prenyl stannylation, a Mukaiyama aldol reaction, an indium mediated
      diastereoselective propargylation, and an advanced stage Stille coupling
      reaction.

PMID- 22594400
TI  - Adiponectin increases insulin content and cell proliferation in MIN6 cells via
      PPARgamma-dependent and PPARgamma-independent mechanisms.
AB  - AIMS: Adiponectin is an important adipokine whose levels are decreased in obesity
      despite increases in adipocyte mass. Studies in animal models implicate
      adiponectin as an insulin sensitizer in skeletal muscle and liver.
      Thiazolidinediones (TZDs) are insulin sensitizers and ligands for peroxisome
      proliferator-activated gamma receptors (PPARgamma) and these receptors are
      expressed in beta cells where their activation promotes cell survival. We
      hypothesize that adiponectin promotes beta cell survival by activating PPARgamma.
      METHODS: We used MIN6 cells to investigate the effect of adiponectin on PPARgamma
      expression, beta-cell proliferation, insulin synthesis and insulin secretion.
      RESULTS: We demonstrate that MIN6 cells contain adiponectin receptors and that
      adiponectin activates PPARgamma mRNA and protein expression. This increase in
      PPARgamma expression is blocked by the PPARgamma antagonist, GW9662, indicating a
      transcriptional feedback loop involving PPARgamma activation of itself.
      Adiponectin causes a significant increase in insulin content and secretion and
      this occurs also via PPARgamma activation due to the inhibitory effect of GW9662.
      Adiponectin also promotes MIN6 cell proliferation, however, this effect is
      independent of PPARgamma activation. CONCLUSIONS: Our results identify novel
      roles for the adipokine, adiponectin, in beta-cells function. Adiponectin
      upregulates PPARgamma expression, insulin content and insulin secretion through
      PPARgamma-dependent mechanisms. Reductions in circulating adiponectin levels in
      obese individuals could therefore result in negative effects on beta-cell
      function and this may have direct relevance to beta-cell dysfunction in type 2
      diabetes.

PMID- 22594401
TI  - Bacterial pathogens related to chronic suppurative otitis media in individuals
      with cleft palate: bacteriological culture and polymerase chain reaction.
AB  - OBJECTIVE: To characterize the microbial etiology of chronic suppurative otitis
      media comparing the methods of classical bacteriological culture and polymerase
      chain reaction. DESIGN/SETTING/PATIENTS: Bacteriological analysis by classical
      culture and by molecular polymerase chain reaction of 35 effusion otitis samples
      from patients with cleft lip and palate attending the Hospital for Rehabilitation
      of Craniofacial Anomalies of the University of Sao Paulo, Bauru, Brazil.
      INTERVENTIONS: Collection of clinical samples of otitis by effusion through the
      external auditory tube. MAIN OUTCOME MEASURE: Otolaryngologic diagnosis of
      chronic suppurative otitis media. RESULTS: Positive cultures were obtained from
      83% of patients. Among the 31 bacterial lineages the following were isolated. In
      order of decreasing frequency: Pseudomonas aeruginosa (54.9%), Staphylococcus
      aureus (25.9%), and Enterococcus faecalis (19.2%). No anaerobes were isolated by
      culture. The polymerase chain reaction was positive for one or more bacteria
      investigated in 97.1% of samples. Anaerobe lineages were detected by the
      polymerase chain reaction method, such as Fusobacterium nucleatum , Bacteroides
      fragilis , and Peptostreptococcus anaerobius . CONCLUSIONS: Patients with cleft
      lip and palate with chronic suppurative otitis media presented high frequency of
      bacterial infection in the middle ear. The classical bacteriological culture did
      not detect strict anaerobes, whose presence was identified by the polymerase
      chain reaction method.

PMID- 22594403
TI  - Editorial: a special tribute to Isabelle Murat and Martin Johr.

PMID- 22594402
TI  - Quantitative evaluation of anterior chamber parameters using anterior segment
      optical coherence tomography in primary angle closure mechanisms.
AB  - BACKGROUND: To evaluate different mechanisms of primary angle closure and to
      quantify anterior chamber parameters in these mechanisms using anterior segment
      optical coherence tomography in an Asian population. DESIGN: Hospital-based cross
      sectional observational study. PARTICIPANTS: Forty-eight consecutive patients
      with primary angle closure glaucoma. METHODS: Patients underwent complete
      ophthalmic examination and imaging of nasal-temporal angles with anterior segment
      optical coherence tomography. Images were categorized into four primary angle
      closure mechanisms: pupil block, plateau iris configuration, Thick peripheral
      iris roll and exaggerated lens vault. Parameters computed: anterior chamber depth
      central, anterior chamber depth at 1000 um and 2000 um anterior to scleral spur,
      lens vault, anterior chamber area, angle opening distance, trabecular iris space
      area and iris thickness. MAIN OUTCOME MEASURE: Anterior chamber parameters and
      primary angle closure mechanisms. RESULTS:   Mean values of anterior chamber
      depths: central (P < 0.001), at 2000 um (P < 0.001), 1000 um (P < 0.001), lens
      vault (P < 0.001), anterior chamber area (P < 0.001), were significantly
      different among the four groups. Multivariate analysis showed anterior chamber
      depths: central, and anterior chamber depth at 2000 um and anterior chamber area
      were higher in plateau iris and Thick peripheral iris roll and lower in
      exaggerated lens vault (P < 0.001) as compared to pupil block mechanism, lens
      vault was greater in exaggerated lens vault (P < 0.001) and lesser in plateau
      iris and Thick peripheral iris roll as compared to pupil block mechanism.
      CONCLUSION: Anterior segment optical coherence tomography may be used for
      evaluation of underlying primary angle closure mechanism(s) in a patient and
      tailor the treatment accordingly.

PMID- 22594404
TI  - The normal and the challenging pediatric airway.
AB  - Management of a child's airway is one of the main sources of stress for
      anesthetists who do not routinely anesthetize children. Unfortunately, trainees
      are gaining less experience in pediatric airway management than in the past,
      which is particularly difficult at a time when some beliefs about airway
      management are being challenged and airway management is less standardized.
      Fortunately, most children have an easily managed, normal airway. Nevertheless,
      it is of vital importance to teach our trainees the basic airway skills that are
      probably the most important skill in an anesthetists' repertoire when it comes to
      a difficult airway situation. This review focuses on the airway management in
      children with a normal and a challenging airway. Different choices of airway
      management in children, and their advantages and disadvantages are discussed.
      Furthermore, the three broad causes of a challenging airway in children and
      infants are highlighted - the difficulty obtaining a mask seal, difficulty
      visualizing the vocal cords, and the third cause in which the larynx can be
      visualized but the difficulty lies at or beyond that level. Guidelines are given
      how to deal with these patients as well as with the feared but rare scenario of
      'cannot ventilate, cannot intubate' in children.

PMID- 22594405
TI  - The pain-free ward: myth or reality.
AB  - Over the last 25 years, pediatric care has changed dramatically with increased
      survival after premature birth, more complex care, better outcomes, and reduced
      mortality. There is a better understanding of how pain pathways and receptor
      systems develop and also how to assess pain at different stages of development.
      The myth that children do not feel pain has been comprehensively dispelled. Safe
      analgesic dose regimens for neonates, infants, and children have been developed
      based upon a better understanding of developmental pharmacokinetics and
      pharmacodynamics. It is a myth that pain in children cannot be prevented or
      treated safely and effectively because of the risks of adverse effects and
      addiction. Large-scale prospective audits have clarified the safety profile and
      risk-benefit balance for different techniques. There is now a substantial
      evidence base supporting many techniques of postoperative and procedural pain
      management for all age-groups of children. Guidelines based upon systematic
      review of this evidence have been published and updated, but the real challenge
      is in implementation of accurate pain assessment and safe, effective pain
      management comprehensively to all children whatever the procedure, clinical
      setting, developmental stage of the child, or comorbidities. In developed
      countries, these are core topics in the education of all doctors and nurses who
      care for children, and they are integrated into clinical practice by acute
      pediatric pain teams for most hospitals. However, it is disappointing that many
      country's healthcare systems do not give pediatric pain management a priority and
      in many parts of the world there are no analgesics available. So pain-free
      healthcare is sadly lacking in many hospitals. My hope is that the current
      knowledge can be used more effectively to relieve the unnecessary suffering of
      children in the 21st century.

PMID- 22594406
TI  - The EEG signal: a window on the cortical brain activity.
AB  - The accurate assessment of the depth of anesthesia, allowing a more accurate
      adaptation of the doses of hypnotics, is an important end point for the
      anesthesiologist. It is a particularly crucial issue in pediatric anesthesia, in
      the context of the recent controversies about the potential neurological
      consequences of the main anesthetic drugs on the developing brain. The
      electroencephalogram signal reflects the electrical activity of the neurons in
      the cerebral cortex. It is thus the key to assessment of the level of hypnosis.
      Beyond visual analysis, several monitoring devices allow an automated treatment
      of the electroencephalographic (EEG) signal, combining time and frequency domain
      analysis. Each of these monitors focuses on a specific combination of
      characteristics of the signal and provides the clinician with useful information
      that remains, however, partial. For a comprehensive approach of the EEG-derived
      indices, the main features of the normal EEG, in adults and children, will be
      presented in the awake state and during sleep. Age-related modifications
      accompanying cerebral maturation during infancy and childhood will be detailed.
      Then, this review will provide an update on how anesthetic drugs, particularly
      hypnotics, influence the EEG signal, and how the main available monitors analyze
      these drug-induced modifications. The relationships between pain, memory, and the
      EEG will be discussed. Finally, this review will focus on some specific EEG
      features such as the electrical epileptoid activity observed under sevoflurane
      anesthesia. The EEG signal is the best window we have on cortical brain activity
      and provides a fair pharmacodynamic feedback of the effects of hypnotics.
      However, the cortex is only one of several targets of anesthesia. Hypnotics and
      opiates, have also subcortical primary targets, and the EEG performances in the
      evaluation or prediction of nociception are poor. Monitoring subcortical
      structures in combination with the EEG might in the future allow a better
      evaluation and a more precise adaptation of balanced anesthesia.

PMID- 22594407
TI  - The new challenging pediatric patient.
AB  - The 'new' challenging pediatric patients are those who could be called 'the
      survivors' and neonates undergoing birth under materno-fetal circulation. Their
      anesthetic management is complex because their initial pathology was previously
      lethal: the physiologic, pharmacologic, and or technical aspect of their
      management is presently unknown or hypothetical. Some examples are described.
      Communication with the pediatrician in charge of the child is the key to safe and
      effective anesthetic care of these cases.

PMID- 22594408
TI  - The future of pediatric anesthesia.
AB  - The future of pediatric anesthesia can be thought of in terms of what will happen
      to the practice of anesthesia, or what will happen to the profession of pediatric
      anesthesia. The profession will change both under external forces, and by how
      pediatric anesthetists themselves decide to shape of the profession. The largest
      external force is likely to be cost. The profession will increasingly be expected
      to maintain efficiency without compromising quality. Other future issues include
      credentialing, training and the role of the anesthetists beyond the operating
      room. It's harder to predict how the practice of pediatric anesthesia might
      change. New drugs may change practice, though perhaps it's more likely that
      practice will change with better use of existing drugs. New technologies will
      have an impact in monitoring and in the gathering and dissemination of
      information. Practice will also change with changes in surgery. Perhaps the
      biggest changes will come in areas with the greatest unknowns; neonatal
      anesthesia is an area with many unknowns and thus great potential for change and
      improvement.

PMID- 22594409
TI  - Pediatric hypnosis: pre-, peri-, and post-anesthesia.
AB  - OBJECTIVE: Pediatric hypnosis has a useful role in pre-, peri-, and post
      anesthesia to minimize anticipatory anxiety, and as adjunctive treatment to
      reduce and control pain. This article reviews the literature in the use of
      hypnosis in pediatric anesthesia to highlight its role and relevancy. BACKGROUND:
      Current research indicates there is an immediate and enduring impact, and long
      term benefits of this child-centered intervention. Hypnosis can be included in
      presurgical consultations to establish cooperation and signals for increasing
      comfort and to address fears and provide suggestions for rapid recovery with
      changed expectations for the child's own benefit. Thus prepared, the child is in
      a heightened state of receptivity and statements and suggestions carry through to
      peri- and post-anesthesia, when hypnosis can help with extubation, reduce nausea,
      and ease recovery. METHOD: The Magic Glove is one hypno-anesthesia technique that
      simultaneously addresses pain and anxiety. The process of hypnosis requires
      training and supervised practice. CONCLUSION: Patients in hypnosis treatment
      conditions have less anxiety and shorter hospital stays and experience less long
      term pain and discomfort than do patients in control conditions. There appears
      little reason not to provide hypnosis as an adjunctive treatment for pediatric
      patients undergoing anesthesia.

PMID- 22594410
TI  - In response to review article by Mazoit, J.-X. (2012), Local anesthetics and
      their adjuncts. Pediatric Anesthesia, 22: 31-38. doi: 10.1111/j.1460
      9592.2011.03692.x.

PMID- 22594412
TI  - The bright side of sedation: 'May the EtCO(2)  be with you!'.

PMID- 22594413
TI  - Pajunk((r))  Tsui StimuLong epidural catheter malfunction.

PMID- 22594414
TI  - Longitudinal ultrasound images of guidewires placed in the internal jugular veins
      of children.

PMID- 22594415
TI  - Giant occipital encephalocele: a new paradigm.

PMID- 22594416
TI  - The air-Q in infant intubation.

PMID- 22594417
TI  - Open safety pin causing fatal pneumopericardium: the effect of positive-pressure
      ventilation.

PMID- 22594418
TI  - Suspected reexpansion pulmonary edema during emergence from general anesthesia in
      a child with developmental dysplasia of the hip.

PMID- 22594419
TI  - New-onset prolonged QTc leading to torsade de pointes in a child with acute liver
      disease.

PMID- 22594420
TI  - Predictors of postoperative sore throat in intubated children.

PMID- 22594422
TI  - Spinal anesthesia is a valid alternative to other anesthetic approaches for
      children with neuromuscular disease, and dexmedetomidine sedation is a safe
      method for pediatric regional anesthesia.

PMID- 22594423
TI  - Strategy for suspected difficult extubation: algorithm and the role of laryngeal
      mask airway, fiberoptic bronchoscope, and airway exchange catheter.

PMID- 22594424
TI  - The use of subcutaneous infusion tumescent anesthesia in photodynamic therapy
      pain control.

PMID- 22594425
TI  - Comment on the case report 'Migrating thoracic epidural catheter in an infant'.

PMID- 22594426
TI  - Dexmedetomidine infusion for sedation in the intensive care setting in an infant
      with airway compromise due to congenital mediastinal neuroblastoma.

PMID- 22594427
TI  - Does the type of anesthesia administered affect the efficacy of medicinal leech
      therapy after finger replantation: clinical observations in a 6-year-old boy.

PMID- 22594428
TI  - Does not topical airway lidocaine before endotracheal intubation decrease the
      risk of perioperative respiratory adverse events in children?

PMID- 22594429
TI  - Interest of ketamine for the management of a large foreign body in the trachea.

PMID- 22594430
TI  - The combination of RACHS-1 and postoperative blood lactate levels is a better
      prognostic mean after pediatric cardiac surgery than each alone.

PMID- 22594432
TI  - Prevalence of sacral spinal (Tarlov) cysts in persistent genital arousal
      disorder.
AB  - INTRODUCTION: Neither consistent etiology nor treatment have been established for
      Persistent Genital Arousal Disorder (PGAD), which is characterized by uninvited,
      unwelcome, and distressing genital sensation. Sacral (Tarlov) cysts, which form
      on dorsal (sensory) roots, most commonly of S2 and S3 in the sacral spine, are
      reported to produce genital symptoms that bear similarities to those described
      for PGAD. AIMS: The present study ascertained the incidence of Tarlov cysts in
      the sacral spine of women with PGAD symptoms. METHODS: Women in a PGAD internet
      support group were asked to submit MRIs of their sacral region to the
      investigators, who evaluated the MRIs for the presence or absence of Tarlov
      cysts. MAIN OUTCOME MEASURES: The presence or absence of Tarlov cysts at the
      level of the sacral spine. RESULTS: Tarlov cysts were present in 12 of the first
      18 (66.7%) MRIs submitted to the investigators by women who suffer from PGAD
      symptoms. By contrast to this incidence, that of Tarlov cysts reported in the
      literature for large samples of the population observed for various disorders
      (e.g., lumbosacral pain) is 1.2-9.0%. CONCLUSION: Tarlov cysts have been
      described in the literature as producing paresthesias and genital sensory
      disturbances. Hence, at least some cases of PGAD might be considered to be a
      Tarlov cyst-induced paresthesia. Based on the relatively high occurrence of
      Tarlov cysts currently observed in women who suffer from PGAD symptoms, it would
      seem advisable to suspect Tarlov cysts as a possible organic etiological factor
      underlying PGAD.

PMID- 22594433
TI  - Preface to supplement, CMA4CH 2010: Multivariate Analysis and Chemometry to
      Cultural Heritage and Environment.

PMID- 22594431
TI  - Lymphotoxin-beta receptor blockade induces inflammation and fibrosis in tolerized
      cardiac allografts.
AB  - The lymphotoxin system (LT) regulates interactions between lymphocytes and
      stromal cells to maintain lymphoid microenvironmental homeostasis. Soluble LT
      beta-receptor-Ig (LTbetaRIg) blocks lymphocyte LTalpha1beta2-stromal cell LTbetaR
      signaling. In a murine cardiac allograft model, LTbRIg treatment reversed the
      tolerance induced by anti-CD40L antibody leading to graft inflammation and
      fibrosis. LTbetaRIg treatment decreased PD-L1 expression by blood endothelial
      cells, and decreased VCAM-1 while increasing CXCL1, CXCL2, CXCL12, CCL5, CCL21
      and IL-6 expression in fibroblastic reticular cells. In secondary lymphoid organs
      these effects caused T- and B cell zone disruption, loss of CD35(+)  follicular
      dendritic cells and abnormal recruitment of CD11b(+) Ly6G(+)  neutrophils. These
      disruptions correlated with increased numbers of CD8(+)  T cells and CD11b(+)
      Ly6G(+)  neutrophils, and decreased numbers of CD4(+)  T cells and Foxp3(+) 
      regulatory T cells in the grafts. Depleting neutrophils or blocking neutrophil
      attracting chemokines restored normal histology in lymph node, spleen and grafts.
      Taken together, LTbetaRIg treatment altered stromal subset, particularly
      fibroblastic reticular cell, production of cytokines and chemokines, resulting in
      changes in neutrophil recruitment in spleen, lymph node and grafts, and
      inflammation and fibrosis associated with decreased Foxp3(+)  regulatory T cells
      and increased CD8(+)  T cell infiltration of grafts.

PMID- 22594434
TI  - Self organising maps for visualising and modelling.
AB  - The paper describes the motivation of SOMs (Self Organising Maps) and how they
      are generally more accessible due to the wider available modern, more powerful,
      cost-effective computers. Their advantages compared to Principal Components
      Analysis and Partial Least Squares are discussed. These allow application to non
      linear data, are not so dependent on least squares solutions, normality of errors
      and less influenced by outliers. In addition there are a wide variety of
      intuitive methods for visualisation that allow full use of the map space. Modern
      problems in analytical chemistry include applications to cultural heritage
      studies, environmental, metabolomic and biological problems result in complex
      datasets. Methods for visualising maps are described including best matching
      units, hit histograms, unified distance matrices and component planes. Supervised
      SOMs for classification including multifactor data and variable selection are
      discussed as is their use in Quality Control. The paper is illustrated using four
      case studies, namely the Near Infrared of food, the thermal analysis of polymers,
      metabolomic analysis of saliva using NMR, and on-line HPLC for pharmaceutical
      process monitoring.

PMID- 22594435
TI  - XPS characterization of (copper-based) coloured stains formed on limestone
      surfaces of outdoor Roman monuments.
AB  - Limestone basements holding bronzes or other copper alloys artefacts such as
      sculptures, decorations and dedicatory inscriptions are frequently met both in
      modern and ancient monuments. In outdoor conditions, such a combination implies
      the corrosion products of the copper based alloy, directly exposed to rainwater,
      will be drained off and migrate through the porous surfaces, forming stains of
      different colours and intensities, finally causing the limestone structures to
      deteriorate.In this work we have analysed samples from two modern limestone
      monuments in Rome, the Botticino surfaces of the 'Vittoriano' (by G.Sacconi, 1885
      1911- Piazza Venezia) and the travertine basement of the 'Statua dello Studente'
      (by A.Cataldi, 1920- University city, La Sapienza), and focussed our
      investigation on the chemical composition of the copper-stained zones using XPS
      (X-ray Photoelectron Spectroscopy) as a surface-specific technique.Based on
      observations reporting on the structure and bonding at the calcite surfaces we
      have identified copper complexes and mixed calcium/copper carbonates associated
      with the stains, as well as the chemical state of other elements therein
      included, and related the compositional changes with differences in chromatic
      characteristics and sampling locations.

PMID- 22594436
TI  - Microclimate monitoring in the Carcer Tullianum: temporal and spatial correlation
      and gradients evidenced by multivariate analysis; first campaign.
AB  - Too often microclimate studies in the field of cultural heritage are published
      without any or scarce information on sampling design, sensors (type, number,
      position) and instrument validation. Lacking of this fundamental information does
      not allow an open discussion in the scientific community. This work aims to be an
      invitation for a different approach.Three main parameters (temperature, humidity,
      luminance) were monitored in a selected part of a complex construction by an
      inexpensive self-assembled system along some horizontal and vertical vectors. All
      data was then processed and analyse by chemometric methods. Some measurements of
      oxygen, carbon monoxide and dioxide and pressure were also performed.Correlation
      of some indoor and outdoor data was shown for temperature and humidity. In case
      of outdoor changes the indoor environment reacted with a certain delay which is
      position-dependent and more evident for humidity data. The two observed rooms
      (Carcer and Tullianum) behave differently and the hypogean one is less influenced
      by the outdoor environment. Instrument validation before and after the campaign,
      allows to consider detected variations as significant.The fundamental importance
      of Sampling Design and of instrument validation before and after the monitoring
      campaign was enhanced. The choice of two main and two minor vectors allowed
      detection of different behaviour for the two rooms, also permitting to detect for
      both rooms a trend towards a spontaneous microclimate necessary for a
      conservation project. In the next campaign we will focus on the choice of the
      best sampling frequency to use more sophisticated statistical methods.

PMID- 22594437
TI  - Characterization of black pigment used in 30 BC fresco wall paint using
      instrumental methods and chemometry.
AB  - BACKGROUND AND METHODS: Several standard powdered black pigments were
      characterized by means of thermogravimetry TG-DTG and allied techniques. These
      pigments were used to make standard plaster frescoes at this purpose prepared.
      The latter ones were subjected to Raman and reflectance analysis. The results
      obtained, together with TG data, were chemometrically processed and used to
      identify an analogous standard fresco fabricated by an unknown commercial black
      pigment, obtaining excellent results. RESULTS: The same colorimetric and
      reflectometric techniques, coupled with suitable chemometric techniques, were
      then successfully used to identify the type of black pigment present in an
      ancient roman fresco of the Imperial Age (30 B.C.). CONCLUSION: TG-DTG resulted
      useful techniques to autenticate powdered black pigments.Colorimetry and Raman,
      but also the only colorimetry, were useful to identify an ancient black pigment
      in situ.

PMID- 22594438
TI  - SEM-EDS investigation on PM10 data collected in Central Italy: Principal
      Component Analysis and Hierarchical Cluster Analysis.
AB  - BACKGROUND: Principal Component Analysis (PCA) and Hierarchical Cluster Analysis
      (HCA) were applied on PM10 particle data in order to: identify particle clusters
      that can be differentiated on the bases of their chemical composition and
      morphology, investigate the relationship among the chemical and morphological
      parameters and evaluate differences among the sampling sites. PM10 was collected
      in 3 different sites in central Italy characterized by different conditions:
      yard, urban and rural sites. The concentration of 20 chemical parameters (C, O,
      Na, Mg, Al, Si, P, Cd, Cl, K, Ca, Sn, Ti, Cr, Mn, Fe, Co, Ni, Cu, Zn) were
      determined by Scanning Electron Microscopy - Energy Dispersive X-ray Spectroscopy
      (SEM-EDS) and the particle images were processed by an image analysis software in
      order to measure: Area, Aspect Ratio, Roundness, Fractal Dimension, Box Width,
      Box Height and Perimeter. RESULT: Results revealed the presence of different
      clusters of particles, differentiated on the bases of chemical composition and
      morphological parameters (aluminosilicates, calcium particles, biological
      particles, soot, cenosphere, sodium chloride, sulphates, metallic particles, iron
      spherical particles). Aluminosilicates and Calcium particles of rural and urban
      sites showed a similar nature due to a mainly natural origin, while those of the
      yard site showed a more heterogeneous composition mainly related to human
      activity. Biological particles and soot can be differentiated on the bases of the
      higher loads of Fractal Dimension, which characterizes soot, and content of Na,
      Mg, Ca, Cl and K which characterize the biological ones. The soot of the urban
      site showed higher loadings of Roundness and Fractal Dimension than the soot
      belonging to the yard and rural sites, this was due to the different life time of
      the particles. The metal particles, characterized mainly by the higher loading of
      iron, were present in two morphological forms: spherical and angular particles.
      The first were generated by a fusion process at high temperature, while the
      second one had crustal origin (those characterized by typical terrigenous
      elements) and also human origin. CONCLUSION: In this work a protocol for the
      morphological-chemical characterization of single particles has been developed.
      SEM analysis allows to classify particles in 10 different families and PCA and
      HCA have provided information about the sources of PM and similarities and
      differences among the sites.

PMID- 22594439
TI  - A quantitative structure- property relationship of gas chromatographic/mass
      spectrometric retention data of 85 volatile organic compounds as air pollutant
      materials by multivariate methods.
AB  - A quantitative structure-property relationship (QSPR) study is suggested for the
      prediction of retention times of volatile organic compounds. Various kinds of
      molecular descriptors were calculated to represent the molecular structure of
      compounds. Modeling of retention times of these compounds as a function of the
      theoretically derived descriptors was established by multiple linear regression
      (MLR) and artificial neural network (ANN). The stepwise regression was used for
      the selection of the variables which gives the best-fitted models. After variable
      selection ANN, MLR methods were used with leave-one-out cross validation for
      building the regression models. The prediction results are in very good agreement
      with the experimental values. MLR as the linear regression method shows good
      ability in the prediction of the retention times of the prediction set. This
      provided a new and effective method for predicting the chromatography retention
      index for the volatile organic compounds.

PMID- 22594440
TI  - Source apportionment of groundwater pollutants in Apulian agricultural sites
      using multivariate statistical analyses: case study of Foggia province.
AB  - BACKGROUND: Ground waters are an important resource of water supply for human
      health and activities. Groundwater uses and applications are often related to its
      composition, which is increasingly influenced by human activities.In fact the
      water quality of groundwater is affected by many factors including precipitation,
      surface runoff, groundwater flow, and the characteristics of the catchment area.
      During the years 2004-2007 the Agricultural and Food Authority of Apulia Region
      has implemented the project "Expansion of regional agro-meteorological network"
      in order to assess, monitor and manage of regional groundwater quality. The total
      wells monitored during this activity amounted to 473, and the water samples
      analyzed were 1021. This resulted in a huge and complex data matrix comprised of
      a large number of physical-chemical parameters, which are often difficult to
      interpret and draw meaningful conclusions. The application of different
      multivariate statistical techniques such as Cluster Analysis (CA), Principal
      Component Analysis (PCA), Absolute Principal Component Scores (APCS) for
      interpretation of the complex databases offers a better understanding of water
      quality in the study region. RESULTS: Form results obtained by Principal
      Component and Cluster Analysis applied to data set of Foggia province it's
      evident that some sampling sites investigated show dissimilarities, mostly due to
      the location of the site, the land use and management techniques and groundwater
      overuse. By APCS method it's been possible to identify three pollutant sources:
      Agricultural pollution 1 due to fertilizer applications, Agricultural pollution 2
      due to microelements for agriculture and groundwater overuse and a third source
      that can be identified as soil run off and rock tracer mining. CONCLUSIONS:
      Multivariate statistical methods represent a valid tool to understand complex
      nature of groundwater quality issues, determine priorities in the use of ground
      waters as irrigation water and suggest interactions between land use and
      irrigation water quality.

PMID- 22594441
TI  - Common plants as alternative analytical tools to monitor heavy metals in soil.
AB  - BACKGROUND: Herbaceous plants are common vegetal species generally exposed, for a
      limited period of time, to bioavailable environmental pollutants. Heavy metals
      contamination is the most common form of environmental pollution. Herbaceous
      plants have never been used as natural bioindicators of environmental pollution,
      in particular to monitor the amount of heavy metals in soil. In this study, we
      aimed at assessing the usefulness of using three herbaceous plants (Plantago
      major L., Taraxacum officinale L. and Urtica dioica L.) and one leguminous
      (Trifolium pratense L.) as alternative indicators to evaluate soil pollution by
      heavy metals. RESULTS: We employed Inductively Coupled Plasma Atomic Emission
      Spectroscopy (ICP-AES) to assess the concentration of selected heavy metals (Cu,
      Zn, Mn, Pb, Cr and Pd) in soil and plants and we employed statistical analyses to
      describe the linear correlation between the accumulation of some heavy metals and
      selected vegetal species. We found that the leaves of Taraxacum officinale L. and
      Trifolium pratense L. can accumulate Cu in a linearly dependent manner with
      Urtica dioica L. representing the vegetal species accumulating the highest
      fraction of Pb. CONCLUSIONS: In this study we demonstrated that common plants can
      be used as an alternative analytical tool for monitoring selected heavy metals in
      soil.

PMID- 22594442
TI  - Detailed kinetic and chemometric study of the cellulose thermal breakdown in
      artificially aged and non aged commercial paper. Different methods for computing
      activation energy as an assessment model in archaeometric applications.
AB  - BACKGROUND: The thermal oxidative degradation of aged and non aged cellulose
      samples of commercial paper was studied using thermogravimetry and derivative
      thermogravimetry under a forced air flow up to 800 degrees C. RESULTS: TG and DTG
      data were processed using two non-isothermal-based model-fitting methods and one
      based on linear least squares to calculate Ea trend values, measured as a
      function of artificially induced sample age. The Ea trends thus obtained were
      compared in order to assess their potential for yielding archaeometric curves. As
      the trends of first two methods show an inversion of the direction between non
      aged cellulose samples and artificially aged samples, while the third method does
      not, an in-depth study was carried out using a multilinearity assumption.
      CONCLUSIONS: The results are discussed and the outcomes indicate that the above
      cited inversion is real and not linked to the method. Additionally, it was
      evidenced that the number of points used for the estimation of linear least
      squares model parameters is of capital importance.

PMID- 22594443
TI  - The determination and role of peroxyacetil nitrate in photochemical processes in
      atmosphere.
AB  - Peroxyacetilnitrates (PAN) is the most characteristic photoxidant of a range of
      secondary pollutants formed by the photochemical reaction of hydrocarbons with
      nitrogen oxides in the atmosphere: it is phytotoxic and shows an increasing role
      in human health effects due to ambient air exposure, especially in presence of
      high ozone concentrations. Because of the similarity of the conditions required
      for their photochemical production PAN is observed in conjunction with elevated
      ozone concentrations. PAN has very low natural background concentrations so it is
      the very specific indicator of anthropogenic photochemical air pollution. In this
      paper we report PAN concentrations determined in Rome urban area during winter-
      and summer-period. PAN measurements were carried out by means of a gas
      chromatograph equipped with an Electron Capture Detector (ECD) detector. For
      identifying the acute episodes of atmospheric photochemical pollutants the
      relationship between PAN and the variable Ox (=NO2+O3) which describes the
      oxidation process evolution is investigated. The role of Volatile Organic
      Compounds and PAN in the ozone formation is investigated as well the issue of
      taking in account the autovehicular emissions for checking the NOx fraction in
      fuel.

PMID- 22594444
TI  - Ancient coins: cluster analysis applied to find a correlation between corrosion
      process and burial soil characteristics.
AB  - Although it is well known that any material degrades faster when exposed to an
      aggressive environment as well as that "aggressive" cannot be univocally defined
      as depending also on the chemical-physical characteristics of material, few
      researches on the identification of the most significant parameters influencing
      the corrosion of metallic object are available.A series of ancient coins, coming
      from the archaeological excavation of Palazzo Valentini (Rome) were collected
      together with soils, both near and far from them, and then analysed using
      different analytical techniques looking for a correlation between the corrosion
      products covering the coins and the chemical-physical soil characteristics. The
      content of soluble salts in the water-bearing stratum and surfacing in the
      archaeological site, was also measured.The obtained results stress the influence
      of alkaline soils on formation of patina. Cerussite, probably due to the
      circulation of water in layers rich in marble and plaster fragments, was the main
      corrosion product identified by X-ray Diffraction (XRD). Copper, lead and
      vanadium were found in soil surrounding coins. By measuring conductivity, pH and
      soluble salts content of the washing solutions from both coins and soils, we
      could easily separate coins coming from different stratigraphic units of the
      site.Data were treated by cluster and multivariate analysis, revealing a
      correlation between part of the coins and the nearby soil samples.

PMID- 22594445
TI  - Ultrasound confirmation of ovulation in mares: a normal corpus luteum or a
      haemorrhagic anovulatory follicle?
AB  - The most common pathological anovulatory condition that occurs spontaneously
      during the breeding season in the mare is the haemorrhagic anovulatory follicle
      (HAF). A relatively high proportion of mares, soon after ovulation, develop a
      corpus haemorrhagicum (CH) with a central lacuna. This type of corpora lutea may
      resemble an HAF, which may complicate the accurate diagnosis of ovulation. The
      main objective of this study was to compare the ultrasound data of mares examined
      frequently with HAFs and CHs to elucidate whether it is possible to distinguish
      them from each other. A total of 135 ovulating mares were classified according to
      the morphology of the corpus luteum (CL) in mares with: a solid CL, a CH with
      small or with large central cavities. Ultrasound characteristics of the
      development of 11 HAF and 13 CHs with a large central cavity were compared. The
      pre-ovulatory follicular diameter of ovulatory mares was significantly correlated
      with the diameter of CH with large central cavities. The percentage of mares with
      post-ovulatory areas eligible to be mistaken with a CH was <25%. Although a
      predictive diagnosis of an HAF/CH can be made on the basis of several
      ultrasonographic endpoints, the only parameter that allows a definitive diagnosis
      is the thickness of the luteal border. This is <3 mm in HAFs in contrast to >5 mm
      in CHs. However, this only applies when the unidentified structure has non
      organized contents.

PMID- 22594447
TI  - Genetic study on developmental dysplasia of the hip.
AB  - BACKGROUND: Developmental dysplasia of the hip (DDH) is a developmental disorder
      of the hip joint that results in an abnormal socket of the femoral head, ranging
      from instability, subluxation and complete dislocation of the hip joint. DDH has
      a considerable genetic component. DESIGN: We reviewed the recent progress on
      genetic study of DDH. RESULTS: By linkage and case-control association studies,
      DDH loci have been identified with several susceptibility genes that involve in
      bone and joint biology; however, no unequivocal genes with global significance
      have been detected. The current problem of the association study in DDH is
      discussed. CONCLUSIONS: By advanced technologies and international collaboration,
      we need to find more susceptibility genes and bridge the gap between genetic
      evidence and molecular mechanisms.

PMID- 22594446
TI  - Post-treatment haemolysis in severe imported malaria after intravenous
      artesunate: case report of three patients with hyperparasitaemia.
AB  - Parenteral artesunate has been shown to be a superior treatment option compared
      to parenteral quinine in adults and children with severe malaria. Little
      evidence, however, is available on long-term safety. Recently, cases of late
      onset haemolysis after parenteral treatment with artesunate have been reported in
      European travellers with imported Plasmodium falciparum malaria. Therefore, an
      extended follow-up of adult patients treated for severe imported malaria was
      started in August 2011 at the University Medical Center Hamburg-Eppendorf. Until
      January 2012, three patients with hyperparasitaemia (range: 14-21%) were included
      for analysis. In all three patients, delayed haemolysis was detected in the
      second week after the first dose of intravenous artesunate. Reticulocyte
      production index remained inadequately low in the 7 - 14 days following the first
      dose of artesunate despite rapid parasite clearance. Post-treatment haemolysis
      after parenteral artesunate may be of clinical relevance in particular in
      imported severe malaria characterized by high parasite levels. Extended follow-up
      of at least 30 days including controls of haematological parameters after
      artesunate treatment seems to be indicated. Further investigations are needed to
      assess frequency and pathophysiological background of this complication.

PMID- 22594448
TI  - Exstrophy polyp is a unique pathology entity.
AB  - Classic bladder exstrophy is a rare congenital malformation occurring with an
      incidence of about 1 in 50 000 live births. Polypoid lesions frequently arise in
      the exstrophic bladder template; this has been well described in the pediatric
      urological literature. These lesions, however, are not as familiar to
      pathologists and oftentimes constitute diagnostic challenges. Careful observation
      revealed that these polyps are unique in their histopathologic appearance, with
      deep penetrating nests of urothelium or cysts and surrounding concentric
      fibrosis. Combining the unique clinical setting, a separate pathologic and
      diagnostic entity should be initiated for this type of polyp; we propose the term
      'bladder exstrophy polyp' or simply an 'exstrophy polyp.'

PMID- 22594449
TI  - Genotypic characterization and safety assessment of lactic acid bacteria from
      indigenous African fermented food products.
AB  - BACKGROUND: Indigenous fermented food products play an essential role in the diet
      of millions of Africans. Lactic acid bacteria (LAB) are among the predominant
      microbial species in African indigenous fermented food products and are used for
      different applications in the food and biotechnology industries. Numerous studies
      have described antimicrobial susceptibility profiles of LAB from different parts
      of the world. However, there is limited information on antimicrobial resistance
      profiles of LAB from Africa. The aim of this study was to characterize 33 LAB
      previously isolated from three different African indigenous fermented food
      products using (GTG)5-based rep-PCR, sequencing of the 16S rRNA gene and species
      specific PCR techniques for differentiation of closely related species and
      further evaluate their antibiotic resistance profiles by the broth microdilution
      method and their haemolytic activity on sheep blood agar plates as indicators of
      safety traits among these bacteria. RESULTS: Using molecular biology based
      methods and selected phenotypic tests such as catalase reaction, CO2 production
      from glucose, colonies and cells morphology, the isolates were identified as
      Lactobacillus delbrueckii, Lactobacillus fermentum, Lactobacillus ghanensis,
      Lactobacillus plantarum, Lactobacillus salivarius, Leuconostoc
      pseudomesenteroides, Pediococcus acidilactici, Pediococcus pentosaceus and
      Weissella confusa. The bacteria were susceptible to ampicillin, chloramphenicol,
      clindamycin and erythromycin but resistant to vancomycin, kanamycin and
      streptomycin. Variable sensitivity profiles to tetracycline and gentamicin was
      observed among the isolates with Lb. plantarum, Lb. salivarius, W. confusa
      (except strain SK9-5) and Lb. fermentum strains being susceptible to tetracycline
      whereas Pediococcus strains and Lb. ghanensis strains were resistant. For
      gentamicin, Leuc. pseudomesenteroides, Lb. ghanensis and Ped. acidilactici
      strains were resistant to 64 mg/L whereas some W. confusa and Lb. plantarum
      strains had a MIC value of 16 mg/L and 32 mg/L respectively. No beta-haemolytic
      activity was observed, however, alpha-haemolytic activity was observed in 27% (9)
      of the strains comprising Lb. salivarius (6), W. confusa (2) and Lb. delbrueckii
      (1) isolates. CONCLUSIONS: The resistance to kanamycin and vancomycin is probably
      an intrinsic feature since similar observations were reported in the literature
      for LAB. Low prevalence of pathogenicity indicator traits were observed among the
      isolates especially with the presence of poor haemolytic activities and they
      could therefore be considered as interesting candidates for selection of starter
      cultures or probiotics for different applications.

PMID- 22594450
TI  - Zfhx1b induces a definitive neural stem cell fate in mouse embryonic stem cells.
AB  - Inducing a stable and predictable program of neural cell fate in pluripotent
      cells in vitro is an important goal for utilizing these cells for modeling human
      disease mechanisms. However, the extent to which in vitro neural specification
      recapitulates in vivo neural specification remains to be fully established. We
      previously demonstrated that in the mouse embryo, activation of fibroblast growth
      factor (FGF) signalling promotes definitive neural stem cell (NSC) development
      through the upregulation of the transcription factor Zfhx1b. Here, we asked
      whether Zfhx1b is similarly required during neural lineage development of
      embryonic stem (ES) cells. Zfhx1b gene expression is rapidly upregulated in mouse
      ES cells cultured in a permissive neural-inducing environment, compared to ES
      cells in a standard pluripotency maintenance environment, and is potentiated by
      FGF signalling. However, overexpression of Zfhx1b in ES cells in maintenance
      conditions, containing serum and leukemia inhibitory factor (LIF), is sufficient
      to induce Sox1 expression, a marker found in neural precursors and to promote
      definitive NSC colony formation. Knockdown of Zfhx1b in ES cells using siRNA did
      not affect the initial transition of ES cells to a neural cell fate, but did
      diminish the ability of these neural cells to develop further into definitive
      NSCs. Thus, our findings using ES cells are congruent with evidence from mouse
      embryos and support a model, whereby intercellular FGF signaling induces Zfhx1b,
      which promotes the development of definitive NSCs subsequent to an initial neural
      specification event that is independent of this pathway.

PMID- 22594451
TI  - Caerulomycins and collismycins share a common paradigm for 2,2'-bipyridine
      biosynthesis via an unusual hybrid polyketide-peptide assembly Logic.
AB  - Caerulomycins (CAEs) and collismycins (COLs), which mainly differ in sulfur
      decoration, are two groups of structurally similar natural products containing a
      2,2'-bipyridine (2,2'-BP) core, derivatives of which have been widely used in
      chemistry. The biosynthetic pathways of CAEs and COLs remain elusive. In this
      work, cloning of the CAE biosynthetic gene cluster allowed us to mine a highly
      conserved gene cluster encoding COL biosynthesis in a  Streptomyces  strain that
      was previously unknown as a 2,2'-BP producer. In vitro and in vivo investigations
      into the biosynthesis revealed that CAEs and COLs share a common paradigm
      featuring an atypical hybrid polyketide synthase/nonribosomal peptide synthetase
      system that programs the 2,2'-BP formation. This likely involves an unusual
      intramolecular cyclization/rearrangement sequence, and a difference in processing
      of the sulfhydryl group derived from the same precursor cysteine drives the
      biosynthetic route toward CAEs or COLs.

PMID- 22594452
TI  - Characterization of the temporal induction of hepatic xenobiotic-metabolizing
      enzymes by glucosinolates and isothiocyanates: requirement for at least a 6 h
      exposure to elicit complete induction profile.
AB  - A mechanism of action of chemopreventive glucosinolates/isothiocyanates,
      established largely in vitro, is to modulate carcinogen-metabolizing enzymes.
      Extrapolation in vivo involves relating in vitro concentrations to plasma/tissue
      concentrations attained in vivo, thus assuming that even transient exposure
      modulates enzyme activity. To test this hypothesis, precision-cut rat liver
      slices were incubated with glucosinolates for up to 24 h, and the O-dealkylation
      of methoxyresorufin and ethoxyresorufin was determined; increased activities were
      observed only at incubations of at least 6 h. To evaluate phase II enzymes,
      isothiocyanates, namely, sulforaphane, erucin, and phenethyl isothiocyanate, were
      similarly incubated; quinone reductase increased after incubation for 6 h or
      longer. When glutathione S-transferase was monitored, the phenethyl
      isothiocyanate-manifested rise necessitated at least a 6 h incubation, whereas in
      the case of sulforaphane and erucin, the activity was elevated after only 2 h. It
      is inferred that a rise in carcinogen-metabolizing enzymes by
      glucosinolates/isothiocyanates necessitates tissue exposure of at least 6 h.

PMID- 22594453
TI  - Fluorescence lifetime of fluorescent proteins as an intracellular environment
      probe sensing the cell cycle progression.
AB  - The fluorescence lifetime of fluorescent proteins is affected by the
      concentration of solutes in a medium, in inverse correlation with local
      refractive index. In this paper, we introduce the concept of using this
      dependence to probe cellular molecular environment and its transformation during
      cellular processes. We employ the fluorescence lifetime of Green Fluorescent
      Protein and tdTomato Fluorescent Protein expressed in cultured cells and probe
      the changes in the local molecular environment during the cell cycle progression.
      We report that the longest fluorescence lifetimes occurred during mitosis.
      Following the cell division, the fluorescence lifetimes of these proteins were
      rapidly shortened. Furthermore the fluorescence lifetime of tdTomato in the
      nucleoplasm gradually increased throughout the span of S-phase and remained
      constantly long until the end of interphase. We interpret the observed
      fluorescence lifetime changes to be derived from changes in concentration of
      macromolecular solutes in the cell interior throughout cell cycle progression.

PMID- 22594454
TI  - Interfacial water facilitates energy transfer by inducing extended vibrations in
      membrane lipids.
AB  - We report the complete assignment of the vibrational spectrum of
      dipalmitoylphosphatidylcholine (DPPC), which belongs to the most ubiquitous
      membrane phospholipid family, phosphatidylcholine. We find that water hydrating
      the lipid headgroups enables efficient energy transfer across membrane leaflets
      on sub-picosecond time scales. The emergence of spatially extended vibrational
      modes upon hydration, underlies this phenomenon. Our findings illustrate the
      importance of collective molecular behavior of biomembranes and reveal that
      hydrated lipid membranes can act as efficient media for the transfer of
      vibrational energy.

PMID- 22594455
TI  - Influence of acute sleep loss on the neural correlates of alerting, orientating
      and executive attention components.
AB  - The Attention Network Test (ANT) is deemed to assess the alerting, orientating
      and executive components of human attention. Capitalizing on the opportunity to
      investigate three facets of attention in a single task, we used functional
      magnetic resonance imaging (fMRI) to assess the effect of sleep deprivation (SD)
      on brain responses associated with the three attentional components elicited by
      the ANT. Twelve healthy volunteers were scanned in two conditions 1 week apart,
      after a normal night of sleep (rested wakefulness, RW) or after one night of
      total sleep deprivation. Sleep deprivation was associated with a global increase
      in reaction times, which did not affect specifically any of the three attention
      effects. Brain responses associated with the alerting effect did not differ
      between RW and SD. Higher-order attention components (orientating and conflict
      effects) were associated with significantly larger thalamic responses during SD
      than during RW. These results suggest that SD influences different components of
      human attention non-selectively, through mechanisms that might either affect
      centrencephalic structures maintaining vigilance or ubiquitously perturb neuronal
      function. Compensatory responses can counter these effects transiently by
      recruiting thalamic responses, thereby supporting thalamocortical function.

PMID- 22594457
TI  - Efficacy of ozone and other treatment modalities for retained placenta in dairy
      cows.
AB  - Retained placenta is a worldwide recognized clinical condition in puerperal cows,
      which can significantly affect their health and fertility. Available treatment
      modalities are often of questionable efficacy or associated with time
      constraints, practicality or monetary considerations for their wide application
      in a routine dairy practice. The objective of this study was to compare and
      assess the efficacy of different treatment options, including a novel ozone
      treatment, for the retained placenta. Two hundred cows diagnosed with retained
      placenta were divided into five treatment groups, each receiving a different
      treatment option. Group A (n = 40) was given a combination treatment of
      intrauterine ozone and parenteral cephalexin; group B (n = 40) was given
      intrauterine ozone; group C (n = 40) was given a combination of parenteral
      cephalexin and intrauterine antibiotic tablets; group D (n = 40) was given only
      parenteral cephalexin and group E (n = 40) was given parenteral prostaglandins in
      11-day intervals. The control group (group Z, n = 200) included cows that gave
      birth without assistance and were not diagnosed with a retained placenta. The
      ozone treatment (groups A and B) was found to be the most effective modality
      resulting in the shortest period of days open, the smallest number of artificial
      inseminations until pregnancy, the smallest number of animals diagnosed with
      fever within 10 days post-calving, the highest percentage of animals pregnant
      within 200 days after calving and the smallest number of animals culled because
      of infertility, when compared to the other treatment groups. The intrauterine
      ozone flush therefore has a potential as an efficacious and cost-effective
      treatment option for retained placenta, with an overall positive effect on
      puerperal health and fertility in cows.

PMID- 22594458
TI  - N-heterocyclic carbene (NHC)-catalyzed highly diastereo- and enantioselective oxo
      Diels-Alder reactions for synthesis of fused pyrano[2,3-b]indoles.
AB  - A chiral N-heterocyclic carbene (NHC)-catalyzed Diels-Alder reaction of 2
      oxoindolin-3-ylidenes and alpha-chloroaldehydes was developed for the synthesis
      of fused pyrano[2,3-b]indoles in good to excellent yields (up to 99%) with high
      cis-diastereoselectivities (>99:1 dr) and enantioselectivities (up to >99% ee).

PMID- 22594459
TI  - Direct visualization of near-fields in nanoplasmonics and nanophotonics.
AB  - Electric fields of nanoscale particles are fundamental to our understanding of
      nanoplasmonics and nanophotonics. Success has been made in developing methods to
      probe the effect of their presence, but it remains difficult to directly image
      optically induced electric fields at the nanoscale and especially when ensembles
      of particles are involved. Here, using ultrafast electron microscopy, we report
      the space-time visualization of photon-induced electric fields for ensembles of
      silver nanoparticles having different sizes, shapes, and separations. The high
      field-of-view measurements enable parallel processing of many particles in the
      ensemble with high throughput of information. Directly in the image, the
      evanescent fields are observed and visualized when the particles are polarized
      with the optical excitation. Because the particle size is smaller than the
      wavelength of light, the near-fields are those of nanoplasmonics and are
      precursors of far-field nanophotonics. The reported results pave the way for
      quantitative studies of fields in ensembles of complex morphologies with the
      nanoparticles being embedded or interfacial.

PMID- 22594460
TI  - Determination of anterior segment changes with Pentacam after phacoemulsification
      in eyes with primary angle-closure glaucoma.
AB  - BACKGROUND: To investigate changes of anterior segment morphology in primary
      angle-closure glaucoma after phacoemulsification using the Pentacam system.
      DESIGN: Prospective, interventional study, Zhongshan Hospital of Sun Yat-sen
      University. PARTICIPANTS: Eighty-five eyes from 60 patients with primary angle
      closure glaucoma undergoing phacoemulsification. METHODS:   Intraocular pressure
      was measured by Goldmann applanation tonometry. Anterior segment morphology was
      assessed using the Pentacam camera. MAIN OUTCOME MEASURES: The intraocular
      pressure, central anterior chamber depth, peripheral anterior chamber depth,
      anterior chamber volume, pupil diameter and anterior chamber angle preoperative
      and 3 months postoperative. RESULTS: A total 78 eyes of 55 patients with primary
      angle-closure glaucoma were included in the analysis. Thirty-two eyes (41.0%) had
      acute primary angle-closure glaucoma, and 46 eyes (59.0%) had chronic primary
      angle-closure glaucoma. In both groups, statistically significant decreases in
      intraocular pressure and increases in anterior chamber volume, central anterior
      chamber depth, peripheral anterior chamber depth and anterior chamber angle
      inferiorly, nasally, temporally and superiorly were observed at 3 months after
      phacoemulsification (all P < 0.001). CONCLUSIONS: Phacoemulsification induces
      significant changes in anterior segment morphology in primary angle-closure
      glaucoma accompanied by a significant fall in intraocular pressure in the short
      term.

PMID- 22594461
TI  - Insulin degludec: four times lower pharmacodynamic variability than insulin
      glargine under steady-state conditions in type 1 diabetes.
AB  - AIMS: Insulin degludec (IDeg) is a new-generation basal insulin with an ultra
      long duration of action. We compared the pharmacodynamic (PD) variability of IDeg
      and insulin glargine (IGlar) under steady-state conditions. METHODS: Day-to-day
      variability in glucose-lowering effect was investigated in 54 subjects with type
      1 diabetes who underwent a 24-h euglycaemic glucose clamp on the 6th, 9th and
      12th day of treatment with 0.4 U/kg of IDeg or IGlar once daily. Within-subject
      variability was estimated using a linear mixed model on log-transformed PD
      endpoints derived from the glucose infusion rate (GIR) profiles during the
      clamps. RESULTS: For IDeg the day-to-day variability in glucose-lowering effect
      was four-times lower than for IGlar for total metabolic effect (AUC(GIR,0
      24h,SS), CV 20% vs. 82%) and for the last 22 h [AUC(GIR,2-24h,SS) (not influenced
      by intravenous insulin during the clamp), CV 22% vs. 92%]. Furthermore, lower
      variability in the maximum effect was observed for IDeg vs. IGlar (GIR(max,SS),
      CV 18% vs. 60%). The lower within-subject variability of IDeg was consistent over
      time (CVs of 33% for AUC(GIR,0-2h,SS), 32% for AUC(GIR,10-12h,SS) and 33% for
      AUC(GIR,22-24h,SS)), whereas the variability of IGlar was higher and increased
      substantially 8 h post-dosing (CVs of 60% for AUC(GIR,0-2h,SS), 135% for
      AUC(GIR,10-12h,SS) and 115% for AUC(GIR,22-24h,SS)). CONCLUSIONS: These results
      show that IDeg has a significantly more predictable glucose-lowering effect from
      day to day than IGlar.

PMID- 22594462
TI  - Rotamers or diastereomers? An overlooked NMR solution.
AB  - The existence of rotamers in a solution of analyte complicates (1)H NMR analysis,
      especially when the presence of diastereomers is also possible. Organic chemists
      have often responded to this problem by conducting variable-temperature (VT) NMR
      experiments, changing NMR solvents, or adding complexing agents. Here, with
      specific examples, we illustrate the use of simple yet widely overlooked chemical
      exchange NMR experiments which allow the nonintrusive rapid distinguishment of
      rapidly equilibrating small molecules such as rotamers from nonequilibrating
      diastereomers.

PMID- 22594463
TI  - Dairy products and calcium intake during pregnancy and dental caries in children.
AB  - BACKGROUND: Maternal nutrition status during pregnancy may affect fetal tooth
      development, formation, and mineralization, and may affect dental caries
      susceptibility in children. We investigated the association between maternal
      intake of dairy products and calcium during pregnancy and the risk of childhood
      dental caries. METHODS: Subjects were 315 Japanese mother-child pairs. Data on
      maternal intake during pregnancy were assessed through a diet history
      questionnaire. Outcome data was collected at 41-50 months of age. Children were
      classified as having dental caries if one or more primary teeth had decayed or
      been filled. RESULTS: Higher maternal cheese intake during pregnancy was
      significantly inversely associated with the risk of dental caries in children,
      showing a clear inverse dose-response relationship; the adjusted odds ratio (OR)
      in comparison of the highest tertile with the lowest was 0.37 (95% confidence
      interval [CI]: 0.17-0.76, P for trend=0.01). The inverse associations between
      maternal intake of total dairy products, yogurt, and calcium during pregnancy and
      the risk of childhood dental caries were of borderline significance: the adjusted
      ORs for the highest tertile of total dairy products, yogurt, and calcium were
      0.51 (95% CI: 0.23-1.09, P for trend=0.07), 0.51 (95% CI: 0.23-1.10, P for
      trend=0.07), and 0.50 (95% CI: 0.23-1.07, P for trend=0.08), respectively. There
      was no evident relationship between maternal milk intake and the risk of
      childhood dental caries. CONCLUSION: These data suggested that high intake of
      maternal cheese during pregnancy may reduce the risk of childhood dental caries.

PMID- 22594464
TI  - The contribution of donor quality to differential graft survival in African
      American and Caucasian renal transplant recipients.
AB  - Although a number of factors contributing to the disparity in graft survival
      between African American (AA) and Caucasian kidney transplant recipients have
      been described, the role of donor quality is less well understood. This study was
      undertaken to determine the impact of donor quality differences on this
      disparity, based on review of UNOS (United Network for Organ Sharing) data on
      deceased donor renal transplantation from 2000 to 2010. Donor quality was
      determined by the kidney donor risk index (DRI), and was compared between AA and
      Caucasian recipients. There were 33,405 Caucasians and 22,577 African Americans
      in the study, with mean DRI of 1.17 versus 1.27 (p < 0.001), respectively. In
      analysis 2,446 recipients of each race matched by propensity scoring (based on
      medical, socioeconomic and immunologic covariates), mean DRI was 1.25 for
      Caucasians and 1.28 (p = 0.02) for AA. The hazard ratio (HR) for graft failure
      associated with AA race was 1.8 (p < 0.001) on unadjusted analysis, and decreased
      to 1.6 (p < 0.001) after matching for DRI. These results indicate a significant
      disparity in quality of kidneys received by African Americans, which propensity
      analysis indicates is partially explained by differences in medical, immunologic
      and socioeconomic factors. Furthermore, this difference in donor quality
      partially accounts for poorer graft survival in African Americans.

PMID- 22594465
TI  - Clinical quality performance in U.S. health centers.
AB  - OBJECTIVE: To describe current clinical quality among the nation's community
      health centers and to examine health center characteristics associated with
      performance excellence. DATA SOURCES: National data from the 2009 Uniform Data
      System. DATA COLLECTION/EXTRACTION METHODS: Health centers reviewed patient
      records and reported aggregate data to the Uniform Data System. STUDY DESIGN: Six
      measures were examined: first-trimester prenatal care, childhood immunization
      completion, Pap tests, low birth weight, controlled hypertension, and controlled
      diabetes. The top 25 percent performing centers were compared with lower
      performing (bottom 75 percent) centers on these measures. Logistic regressions
      were utilized to assess the impact of patient, provider, and institutional
      characteristics on health center performance. PRINCIPAL FINDINGS: Clinical care
      and outcomes among health centers were generally comparable to national averages.
      For instance, 67 percent of pregnant patients received timely prenatal care
      (national = 68 percent), 69 percent of children achieved immunization completion
      (national = 67 percent), and 63 percent of hypertensive patients had blood
      pressure under control (national = 48 percent). Depending on the measure, centers
      with more uninsured patients were less likely to do well, while centers with more
      physicians and enabling service providers were more likely to do well.
      CONCLUSIONS: Health centers provide quality care at rates comparable to national
      averages. Performance may be improved by increasing insurance coverage among
      patients and increasing the ratios of physicians and enabling service providers
      to patients.

PMID- 22594466
TI  - Neoplastic leptomeningitis presenting in a melanoma patient treated with
      dabrafenib (a V600EBRAF inhibitor): a case report.
AB  - INTRODUCTION: Leptomeningeal metastases are occurring at higher frequency in
      cancer patients. The prognosis of leptomeningeal metastases is poor and standard
      treatment, which includes radiotherapy and chemotherapy, is mostly ineffective.
      Melanoma represents one of the tumors with the highest incidence of
      leptomeningeal metastases. For such a disease, the BRAF inhibitors have recently
      been demonstrated to be effective on melanoma brain metastases harboring the
      V600EBRAF mutation. CASE PRESENTATION: We report a case of a 39-year-old Italian
      woman with advanced melanoma with brain, lung and peritoneum metastases harboring
      the V600EBRAF mutation. In August 2010 she was enrolled into the BRIM3 trial and
      after the randomization process she received dacarbazine. After two cycles, there
      was evidence of disease progression in her peritoneum and lung. For this reason,
      she was enrolled into another clinical trial with the GSK2118436 BRAF inhibitor,
      dabrafenib, as a second line of therapy. She had a partial response that was
      maintained until 13 weeks of treatment. In January 2011 she developed symptoms
      typical for brain metastases and received a diagnosis of leptomeningeal
      involvement of melanoma cells after an examination of her cerebral spinal fluid;
      magnetic resonance imaging was negative for meningitis or brain metastases.
      Analysis of her cerebral spinal fluid sample confirmed that the melanoma cells
      still carried the V600EBRAF mutation. After a few days, our patient went into a
      coma and died. CONCLUSION: Starting with a clinical case, we discuss the
      pathogenesis of leptomeningeal metastases and whether the leptomeninges may
      represent a sanctuary where melanoma cells may generate resistance and/or BRAF
      inhibitors cannot reach an adequate concentration for significant activity. We
      assess whether treatment with BRAF inhibitors in melanoma patients should be
      interrupted as soon as disease progression appears or continued beyond
      progression, through the administration of additional compounds.

PMID- 22594467
TI  - Onset time for pharmacologic premedication with clonidine as a nasal aerosol: a
      double-blind, placebo-controlled, randomized trial.
AB  - OBJECTIVES/AIM: To investigate whether nasal aerosol clonidine can reduce the
      onset time of preoperative sedation. BACKGROUND: Premedication is common in the
      pediatric population, but the optimal agent and administration route is still a
      matter of debate. Clonidine has many beneficial effects in the perioperative
      period. Clonidine nasal drops produce a similar sedative effect as after oral
      administration but do not reduce the onset time. Nasal aerosol administration of
      drugs is generally more effective than drops and an option to decrease the onset
      time of clonidine. METHODS: Pediatric ASA status 1 and 2 patients were randomized
      to receive placebo (P), clonidine 3-4 MUg kg(-1) (C4), or clonidine 7-8 MUg kg(
      1) (C7) as a nasal aerosol. Acceptance of administration, pre- and postoperative
      sedation, and adverse events were assessed. RESULTS: A total of 60 patients were
      enrolled with a median age of 3.5 years (range 0.7-6.9) and median weight of 14.8
      kg (range 10-25). In the C7 group, 55% of the children were found adequately
      sedated at 30 min as compared to 32% in the C4 group (P = 0.1202). At 45 min,
      adequate sedation was seen in 65% of the patients in both C4 and C7 groups, which
      were both found to be significantly higher compared with the placebo control
      group (14%) (P-values = 0.0027 and 0.0013, respectively). The postoperative
      sedation profile did not differ between the three study groups. CONCLUSIONS:
      Clonidine administered as nasal aerosol (3-8 MUg kg(-1)) was not found to achieve
      adequate preoperative sedation within 30 min of administration. Despite its
      sedative properties, no prolongation of postoperative sedation was noted compared
      with placebo.

PMID- 22594468
TI  - Alcohol use, daily hassles, and religious coping among students at a religiously
      affiliated college.
AB  - OBJECTIVE: This article presents empirical findings which suggest that religious
      coping moderates the relationship between daily hassles stress and alcohol use
      among female college students. METHOD: This study utilized a cross-sectional data
      collection strategy and convenience sampling to examine the relationship between
      alcohol use, daily hassles stress, and religious coping among 423 undergraduate
      students (269 females and 154 males) at a religiously affiliated college in the
      Midwestern USA. Data were collected in 2008. Instruments utilized for data
      collection included the Inventory of College Student Recent Life Experiences, the
      Brief RCOPE, and quantity/frequency measures of alcohol use. RESULTS: Involvement
      in positive religious coping was significantly related to lower rates of alcohol
      use. Hierarchical multiple regression analysis revealed that among women,
      positive religious coping moderated the relationship between two types of daily
      hassles stress (academic alienation and romantic problems) and alcohol use.
      CONCLUSIONS: This study found that among female college students, the
      relationship between daily hassles stress and alcohol use weakened with increased
      participation in religious coping. This finding suggests that religious coping
      may protect against alcohol use among female college students. The results of
      this study also suggest that it may be important for university-based treatment
      and prevention practitioners to assess involvement in religious coping practices
      and to include such practices in the treatment planning process, when culturally
      appropriate and desired by consumers. Study limitations and areas for further
      research are also discussed.

PMID- 22594469
TI  - Editorial : Natural products as anti-cancer agents: understanding their mechanism
      of action.

PMID- 22594470
TI  - Pro-oxidant natural products as anticancer agents.
AB  - Cancer cells produce high levels of reactive oxygen species (ROS) that lead to a
      state of increased basal oxidative stress. Since this state of oxidative stress
      makes cancer cells vulnerable to agents that further augment ROS levels, the use
      of pro-oxidant agents is emerging as an exciting strategy to selectively target
      tumor cells. Natural products have provided a significant contribution to the
      development of several drugs currently used in cancer chemotherapy. Although many
      natural products are known to affect the redox state of the cell, most studies on
      these compounds have focused on their antioxidant activity instead of on their
      pro-oxidant properties. This article provides an overview of natural products
      with pro-oxidant and anticancer activities, with special focus on plant secondary
      metabolites, and discusses their possible use as cancer chemotherapeutic agents.

PMID- 22594472
TI  - New anticancer drugs from marine cyanobacteria.
AB  - Marine Cyanobacteria have raised growing attention as sources of bioactive
      "secondary metabolites" that originate from mixed biosynthetic pathways. Some of
      these molecules exhibit antitumour activities with unique mechanism of action.
      This mini-review focuses specifically on new molecules that may act as leads for
      novel drug development.

PMID- 22594473
TI  - Targeting cancer stem cells with natural products.
AB  - The cancer stem cell (CSC) hypothesis presents a fundamentally different paradigm
      for cancer treatment. CSCs reflect a small fraction of tumor initiating cells
      capable of sustained self-renewal and differentiation to form the heterogeneous
      tumor bulk. In order to cure cancer, it is necessary to eliminate cancer stem
      cells in addition to differentiated cancer cells to decrease metastasis, reduce
      recurrence, and improve patient survival. In this article, we review cancer stem
      cell signaling pathways, including Wnt, Hedgehog, and Notch, as well as
      interactions of CSCs with the tumor microenvironment. We also review methods to
      isolate CSCs and demonstrate therapeutic efficacy of natural products to modulate
      these signaling pathways for eliminating CSCs.

PMID- 22594474
TI  - Vinorelbine in cancer therapy.
AB  - Vinorelbine is an antimitotic anticancer agent and its main mechanism of action
      is related to the inhibition of microtubule dynamics leading to a mitotic arrest
      and cell death. Vinorelbine, as a microtubule destabilizing agent, stimulates
      microtubule depolymerization and mitotic spindle destruction at high
      concentration whereas at lower concentrations, it is able to block mitotic
      progression. Its main targets are tubulin and microtubules. Vinorelbine binds to
      beta-tubulin subunits at Vinca-binding domain near the positive end of
      microtubules. The rapid and reversible binding by Vinorelbine to soluble tubulin
      induces a conformational change that increases the affinity of tubulin for itself
      which plays a key role in the kinetics of microtubule stabilization. This binding
      significantly reduces the rate of microtubule dynamics (lengthening and
      shortening) and increases the duration which microtubules spend in an attenuated
      state. This helps in proper assembly of the mitotic spindle and hence reduces the
      tension at the kinetochores of the chromosomes. Subsequently, chromosomes at the
      spindle poles are unable to progress to the spindle equator. The aim of this
      review is to examine the mechanism of the inhibition of cell proliferation by
      Vinorelbine and its efficacy in breast cancer patients in phase II studies.

PMID- 22594471
TI  - Discovery and mechanism of natural products as modulators of histone acetylation.
AB  - Small molecules that modulate histone acetylation by targeting key enzymes
      mediating this posttranslational modification - histone acetyltransferases and
      histone deacetylases - are validated chemotherapeutic agents for the treatment of
      cancer. This area of research has seen a rapid increase in interest in the past
      decade, with the structurally diverse natural products-derived compounds at its
      forefront. These secondary metabolites from various biological sources target
      this epigenetic modification through distinct mechanisms of enzyme regulation by
      utilizing a diverse array of pharmacophores. We review the discovery of these
      compounds and discuss their modes of inhibition together with their downstream
      biological effects.

PMID- 22594475
TI  - Seek and destroy: the use of natural compounds for targeting the molecular roots
      of cancer.
AB  - One of the major issues facing anticancer research relies on the intrinsic
      inability of tumor cells to undergo apoptosis. Additionally, the development of
      cancer resistance to standard therapy and the great heterogeneity associated with
      frequent mutations and epigenetic changes make an ever increasing challenge to
      achieve treatment success. Thus, novel therapeutic approaches to induce cancer
      demise must be explored. Compelling evidence has shown the ability of naturally
      occurring compounds to modulate signal transduction pathways, apoptosis and cell
      cycle progression, supporting their relevance to anticancer drug discovery.
      Moreover, millions of years of biological selection have led to an unlimited
      repertoire of chemical structures unmatched by any synthetic combinatorial
      library and recent advances in the fields of chemistry and biology are uncovering
      this still underexplored source of new promising natural agents, opening novel
      perspectives for the development of alternative strategies to fight cancer. This
      review presents the current status of natural products in modern oncology,
      illustrating the importance of some old and new agents, such as antimitotics and
      apoptosis inducers, as candidates of pharmacological interest in drug development
      and/or as chemical tools for the elucidation, as well as targeting, of
      deregulated cancer signaling pathways. Finally, some aspects of chemical
      modifications done in natural products core aiming to improve their activity
      and/or effectiveness will be discussed.

PMID- 22594476
TI  - Recent developments in the pharmacological properties of 4'-geranyloxyferulic
      acid, a colon cancer chemopreventive agent of natural origin.
AB  - 3-(4'-Geranyloxy-3'-methoxyphenyl)-2-trans propenoic acid (4'-geranyloxyferulic
      acid, GOFA) is a secondary metabolite biosynthetically related to ferulic acid in
      which a geranyl chain is attached to the phenolic group, extracted in 1966 from
      Acronychia baueri Schott (Fam. Rutaceae). In the last decade the pharmacological
      properties of the title compound began to be characterized, revealing its good
      activity as anti-inflammatory and dietary feeding cancer chemopreventive agent.
      The aim of this review is to examine in detail the recently reported properties
      of 4'-geranyloxyferulic acid from a chemical and pharmacological point of view,
      including the recent acquisition about its mechanism of action.

PMID- 22594477
TI  - Gene expression of tendon collagens and tenocyte markers in long-term monolayer
      and high-density cultures of rat tenocytes.
AB  - As a result of repeated movement, tendons are functionally open to traumas.
      According to this situation, tenocytes have already been used for tissue
      engineering therapies. It has been reported that long-term monolayer (ML) culture
      of tenocytes may lead to a phenotypic drift within passages. Depending on our
      previously published work, it is clearly demonstrated that high-density (HD)
      culture improves cell growth and differentiation of tenocytes. However, it is not
      yet established if HD favors the differentiated state during long-term culture.
      Therefore, we compared the differences in gene expression of tendon collagens and
      tendon markers of tenocytes from long-term ML and HD culture conditions by
      quantitative, real-time polymerase chain reaction (QRT-PCR) for over a period of
      3 weeks. COLI, COLIII, COLV, Scx, and Tnmd were target genes as the major matrix
      constituents of tendons as well as being involved in matrix integrity and
      tenocyte phenotype. According to our results, tenocytes in HD culture synthesized
      less amounts of COLIII, COLV, and Tnmd, and dependent on the investigation time
      point, higher amounts of Scx. We consider that tenocytes produced in HD culture
      system may not provide sufficient efficiency during tissue engineering
      approaches. By the fact that most molecules showed significantly higher
      expression profiles in ML culture condition, it is suggested that culture and
      passage in ML should be taken into consideration for further tissue engineering
      approaches to maintain a phenotype with less amount of drift.

PMID- 22594479
TI  - Aryl and NHC compounds of technetium and rhenium.
AB  - Air- and water-stable phenyl complexes with nitridotechnetium(V) cores can be
      prepared by straightforward procedures. [TcNPh(2)(PPh(3))(2)] is formed by the
      reaction of [TcNCl(2)(PPh(3))(2)] with PhLi. The analogous N-heterocyclic carbene
      (NHC) compound [TcNPh(2)(HL(Ph))(2)], where HL(Ph) is 1,3,4-triphenyl-1,2,4
      triazol-5-ylidene, is available from (NBu(4))[TcNCl(4)] and HL(Ph) or its methoxo
      protected form. The latter compound allows the comparison of different Tc-C bonds
      within one compound. Surprisingly, the Tc chemistry with such NHCs does not
      resemble that of corresponding Re complexes, where CH activation and
      orthometalation dominate.

PMID- 22594478
TI  - An extracellular Staphylococcus epidermidis polysaccharide: relation to
      Polysaccharide Intercellular Adhesin and its implication in phagocytosis.
AB  - BACKGROUND: The skin commensal and opportunistic pathogen Staphylococcus
      epidermidis is a leading cause of hospital-acquired and biomaterial-associated
      infections. The polysaccharide intercellular adhesin (PIA), a homoglycan composed
      of beta-1,6-linked N-acetylglucosamine residues, synthesized by enzymes encoded
      in icaADBC is a major functional factor in biofilm accumulation, promoting
      virulence in experimental biomaterial-associated S. epidermidis infection.
      Extracellular mucous layer extracts of S. epidermidis contain another major
      polysaccharide, referred to as 20-kDa polysaccharide (20-kDaPS), composed mainly
      out of glucose, N-acetylglucosamine, and being partially sulfated. 20-kDaPS
      antiserum prevents adhesion of S. epidermidis on endothelial cells and
      development of experimental keratitis in rabbits. Here we provide experimental
      evidence that 20-kDaPS and PIA represent distinct molecules and that 20-kDaPS is
      implicated in endocytosis of S. epidermidis bacterial cells by human monocyte
      derived macrophages. RESULTS: Analysis of 75 clinical coagulase-negative
      staphylococci from blood-cultures and central venous catheter tips indicated that
      20-kDaPS is expressed exclusively in S. epidermidis but not in other coagulase
      negative staphylococcal species. Tn917-insertion in various locations in icaADBC
      in mutants M10, M22, M23, and M24 of S. epidermidis 1457 are abolished for PIA
      synthesis, while 20-kDaPS expression appears unaltered as compared to wild-type
      strains using specific anti-PIA and anti-20-kDaPS antisera. While periodate
      oxidation and dispersin B treatments abolish immuno-reactivity and intercellular
      adhesive properties of PIA, no abrogative activity is exerted towards 20-kDaPS
      immunochemical reactivity following these treatments. PIA polysaccharide I
      containing fractions eluting from Q-Sepharose were devoid of detectable 20-kDaPS
      using specific ELISA. Preincubation of non-20-kDaPS-producing clinical strain
      with increasing amounts of 20-kDaPS inhibits endocytosis by human macrophages,
      whereas, preincubation of 20-kDaPS-producing strain ATCC35983 with 20-kDaPS
      antiserum enhances bacterial endocytosis by human macrophages. CONCLUSIONS: In
      conclusion, icaADBC is not involved in 20-kDaPS synthesis, while the chemical and
      chromatographic properties of PIA and 20-kDaPS are distinct. 20-kDaPS exhibits
      anti-phagocytic properties, whereas, 20-kDaPS antiserum may have a beneficial
      effect on combating infection by 20-kDaPS-producing S. epidermidis.

PMID- 22594481
TI  - Distribution of HLA-DRB1 and HLA-DQB1 families of alleles and haplotypes in
      Vojvodina population.
AB  - Major histocompatibility complex encoding human leucocyte antigens (HLA) is a
      highly polymorphic gene cluster that makes it a valuable tool in the population
      genetic studies. The aim of our study was to compare HLA class II gene
      frequencies with other populations from Europe and to determine the relationship
      between the investigated populations. In this study, one hundred and twenty
      healthy individuals from Vojvodina, northern Serbia, were studied for 18 of the
      HLA-DRB1 and HLA-DQB1 loci. The HLA families of alleles were analysed by using
      sequence-specific primers for polymerase chain reaction (PCR-SSP). The results
      showed the increased frequency of HLA-DRB1*11(0.333), -DRB1*04(0.300), 
      DRB1*07(0.250), -DQB1*03(0.730) and -DQB1* 05(0.391), among the tested families
      of alleles. The two-locus haplotype analysis revealed significant positive
      linkage disequilibrium for DRB1*11DQB1*03 (Delta = 0.0788, chi(2) = 12.61) and
      DRB1*04DQB1*03 (Delta = 0.0583, chi(2) = 8.04). A phylogenetic tree constructed
      on the basis of the DRB1* gene frequencies derived from other populations
      revealed the clustering among the Vojvodina population together with other
      populations in Europe (Croats, Austrians and Hungarians). Close relationship of
      the Vojvodina population with the populations of Hungarians and Austrians can be
      the result of their historical influence on the region of Vojvodina.

PMID- 22594480
TI  - Development of a highly selective c-Src kinase inhibitor.
AB  - Generating highly selective probes to interrogate protein kinase function in
      biological studies remains a challenge, and new strategies are required. Herein,
      we describe the development of the first highly selective and cell-permeable
      inhibitor of c-Src, a key signaling kinase in cancer. Our strategy involves
      extension of traditional inhibitor design by appending functionality proposed to
      interact with the phosphate-binding loop of c-Src. Using our selective inhibitor,
      we demonstrate that selective inhibition is significantly more efficacious than
      pan-kinase inhibition in slowing the growth of cancer cells. We also show that
      inhibition of c-Abl kinase, an off-target of most c-Src inhibitors, promotes
      oncogenic cell growth.

PMID- 22594482
TI  - Prenatal ultrasound and MRI Diagnosis of Jeune syndrome type I (asphyxiating
      thoracic dystrophy) with histology and post-mortem three-dimensional CT
      confirmation.
AB  - Asphyxiating thoracic dystrophy (ATD) also known as Jeune syndrome is a rare
      autosomal recessive multisystem disorder with an incidence estimated in 1:100.000
      130.000 live births. Associated findings may include hepatic fibrosis and renal
      cysts. A prenatal ultrasound and MRI diagnosis performed in the early second
      trimester of pregnancy is reported together with DNA analysis. Post-mortem
      diagnostic investigations such as radiograph and three-dimensional CT scan and
      histology have been useful in the final diagnosis of this rare skeletal
      dysplasia.

PMID- 22594483
TI  - Review of methane mitigation technologies with application to rapid release of
      methane from the Arctic.
AB  - Methane is the most important greenhouse gas after carbon dioxide, with
      particular influence on near-term climate change. It poses increasing risk in the
      future from both direct anthropogenic sources and potential rapid release from
      the Arctic. A range of mitigation (emissions control) technologies have been
      developed for anthropogenic sources that can be developed for further
      application, including to Arctic sources. Significant gaps in understanding
      remain of the mechanisms, magnitude, and likelihood of rapid methane release from
      the Arctic. Methane may be released by several pathways, including lakes,
      wetlands, and oceans, and may be either uniform over large areas or concentrated
      in patches. Across Arctic sources, bubbles originating in the sediment are the
      most important mechanism for methane to reach the atmosphere. Most known
      technologies operate on confined gas streams of 0.1% methane or more, and may be
      applicable to limited Arctic sources where methane is concentrated in pockets.
      However, some mitigation strategies developed for rice paddies and agricultural
      soils are promising for Arctic wetlands and thawing permafrost. Other mitigation
      strategies specific to the Arctic have been proposed but have yet to be studied.
      Overall, we identify four avenues of research and development that can serve the
      dual purposes of addressing current methane sources and potential Arctic sources:
      (1) methane release detection and quantification, (2) mitigation units for small
      and remote methane streams, (3) mitigation methods for dilute (<1000 ppm) methane
      streams, and (4) understanding methanotroph and methanogen ecology.

PMID- 22594484
TI  - Charge transfer effects in the GroEL-GroES chaperonin tetramer in solution.
AB  - In this work, we present the results of a large-scale, semiempirical LocalSCF
      quantum mechanical study of GroEL-GroES chaperonin in solution containing
      2,481,723 atoms. We find that large biological systems exhibit strong quantum
      mechanical character, the extent of which was not previously known. Our data show
      that protein transfers -743 electron units of charge to solvent, which is not
      described by classical force fields. Contrary to the commonly held belief, which
      is based on classical mechanics, our computational data suggest that the quantum
      mechanical effects of charge transfer increase with the size of biological
      systems. We show that the neglect of charge transfer in classical force fields
      leads to significant error in the electrostatic potential of the macromolecule.
      These findings illustrate that a quantum mechanical framework is necessary for a
      realistic description of electrostatic interactions in large biological systems.

PMID- 22594485
TI  - Oxidized derivatives of dihydrobrassicasterol: cytotoxic and apoptotic potential
      in U937 and HepG2 cells.
AB  - The ability of phytosterol compounds to reduce plasma serum cholesterol levels in
      humans is well investigated. However, phytosterols are structurally similar to
      cholesterol with a double bond at the C5-6 position and are therefore susceptible
      to oxidation. Much research has been carried out on the biological effects of
      cholesterol oxidation products (COPs) in vitro. In contrast, there is less known
      about phytosterol oxidation products (POPs). From previous studies, it is
      apparent that oxidized derivatives of the phytosterols, beta-sitosterol and
      stigmasterol, are cytotoxic in vitro but are less potent than their COP
      counterparts. In the present study, the cytotoxic and apoptotic potential of
      oxidized derivatives of dihydrobrassicasterol (DHB) including 5alpha,6alpha
      epoxyergostan-3beta-ol (alpha-epoxide), 5beta,6beta-epoxyergostan-3beta-ol (beta
      epoxide), ergost-5-en-7-on-3beta-ol (7-keto), ergost-5-ene-3beta,7beta-diol (7
      beta-OH), and ergostane-3beta,5alpha,6beta-triol (triol) were evaluated in the
      U937 and HepG2 cell lines. In general, 7-keto, 7-beta-OH, and triol derivatives
      had a significant cytotoxic impact on U937 and HepG2 cells. The oxides appear to
      be more toxic toward U937 cells. In line with previous findings, the POPs
      investigated in this study were less potent than the equivalent COPs. The results
      add to the body of data on the toxicity of individual POPs. 

PMID- 22594486
TI  - Adoption of diagnostic technology and variation in caesarean section rates: a
      test of the practice style hypothesis in Norway.
AB  - OBJECTIVE: To examine whether the introduction of advanced diagnostic technology
      in maternity care has led to less variation in type of delivery between hospitals
      in Norway. DATA SOURCES: The Medical Birth Registry of Norway provided detailed
      medical information for 1.7 million deliveries from 1967 to 2005. Information
      about diagnostic technology was collected directly from the maternity units.
      STUDY DESIGN: The data were analyzed using a two-level binary logistic model with
      Caesarean section as the outcome measure. Level one contained variables that
      characterized the health status of the mother and child. Hospitals are level two.
      A heterogeneous variance structure was specified for the hospital level, where
      the error variance was allowed to vary according to the following types of
      diagnostic technology: two-dimensional ultrasound, cardiotocography, ST waveform
      analysis, and fetal blood analyses. PRINCIPAL FINDING: There was a marked
      variation in Caesarean section rates between hospitals up to 1973. After this the
      variation diminished markedly. This was due to the introduction of ultrasound and
      cardiotocography. CONCLUSION: Diagnostic technology reduced clinical uncertainty
      about the diagnosis of risk factors of the mother and child during delivery, and
      variation in type of delivery between hospitals was reduced accordingly. The
      results support the practice style hypothesis.

PMID- 22594487
TI  - Development and validation of a multi-body model of the canine stifle joint.
AB  - Multi-body musculoskeletal models that can be used concurrently to predict joint
      contact pressures and muscle forces would be extremely valuable in studying the
      mechanics of joint injury. The purpose of this study was to develop an
      anatomically correct canine stifle joint model and validate it against
      experimental data. A cadaver pelvic limb from one adult dog was used in this
      study. The femoral head was subjected to axial motion in a mechanical tester.
      Kinematic and force data were used to validate the computational model. The
      maximum RMS error between the predicted and measured kinematics during the
      complete testing cycle was 11.9 mm translational motion between the tibia and the
      femur and 4.3 degrees  rotation between patella and femur. This model is the
      first step in the development of a musculoskeletal model of the hind limb with
      anatomically correct joints to study cartilage loading under dynamic conditions.

PMID- 22594488
TI  - Correlation of structural retinal nerve fibre layer parameters and functional
      measures using Heidelberg Retinal Tomography and Spectralis spectral domain
      optical coherence tomography at different levels of glaucoma severity.
AB  - BACKGROUND: To compare the structure/function relationship in glaucoma cases at
      different levels of severity, and with different disc sizes, between the
      Heidelberg Retinal Tomography and Spectralis spectral domain optical coherence
      tomography. DESIGN: Retrospective study of glaucoma patients attending a Sydney
      based private practice. PARTICIPANTS: 169 eyes of 169 patients with a clinical
      diagnosis of glaucoma. METHODS: Patients were divided on visual field criteria
      into early (mean deviation > -4 dB), moderate (-4 dB < mean deviation < -10 dB)
      and severe (mean deviation < -10 dB) disease. Bivariate correlation (Spearman's
      rho) between mean threshold scores for each area and the corresponding mean
      retinal nerve fibre layer thickness sectoral measurement were calculated. MAIN
      OUTCOME MEASURES: Correlation, as measured by Spearman's rho, between retinal
      nerve fibre layer measurements and mean threshold scores. Comparison of
      correlation strengths between the two scanning modalities with analysis of the
      effect of disease severity and disc size. RESULTS: Both imaging techniques showed
      only moderate correlations at best. Spectral domain optical coherence tomography
      (global retinal nerve fibre layer Spearman's rho = 0.670, P < 0.01) had higher
      correlation coefficients compared with Heidelberg Retinal Tomography rim area
      (Spearman's rho = 0.449, P < 0.01) and retinal nerve fibre layer (Spearman's rho
      = 0.421, P < 0.01). Disc size did not have a significant influence on the
      structure/function relationship. CONCLUSIONS: Spectral domain optical coherence
      tomography retinal nerve fibre layer measurements demonstrated closer
      correlations to visual field threshold reductions using a structure/function
      model in varying stages of glaucoma.

PMID- 22594489
TI  - New treatment for faecal incontinence using zinc-aluminium ointment: a double
      blind randomized trial.

PMID- 22594490
TI  - Up-regulation of insulin-like growth factor I and uteroglobin in in vivo
      developed parthenogenetic embryos.
AB  - Parthenote embryos are being considered as an alternative source of embryonic
      stem cells. However, as there is still a dearth of knowledge of this kind of
      embryos, a better understanding of their biology is needed for their application.
      In this work, we studied the differences and similarities between parthenotes and
      normal embryos at the blastocyst stage in vivo developed. We analysed the
      expression of factor OCT-4, vascular endothelial growth factor (VEGF), insulin
      like growth factor I (IGF-I) and uteroglobin (UG) by real-time PCR. To do so,
      oocytes were recovered and after activation procedure were transferred by ventral
      middle laparoscopy to receptive does to undergo completely in vivo development.
      Does were slaughtered 6 days post-ovulation induction, and parthenote and normal
      embryos were recovered for mRNA expression analysis. Our results reported that
      parthenotes and normal embryos showed similar mRNA expression for OCT-4 and VEGF.
      However, IGF-I and UG showed to be over-expressed in parthenote embryos. Thus,
      our study highlights that despite the in vivo development of parthenotes, they
      still seem to have an altered expression and, therefore, to be different to
      normal embryos. The altered expression pattern of parthenote embryos suggests
      that these embryos should be studied carefully before future application.

PMID- 22594492
TI  - Can the government ban organ sale? Recent court challenges and the future of US
      law on selling human organs and other tissue.
AB  - On December 1, 2011, in Flynn v. Holder, a panel of the US Court of Appeals for
      the Ninth Circuit upheld the National Organ Transplant Act of 1984 (NOTA) from a
      constitutional challenge, but interpreted the act such that its prohibition on
      sale did not encompass "peripheral blood stem cells" obtained through apheresis.
      Rehearing of the case was denied on March 27, 2012. The Obama administration must
      now decide whether to pursue its challenge in the US Supreme Court. This article
      explains the litigation, its significance and uses it as a backdrop against which
      to understand the history and future trajectory of the laws governing selling
      organs and other human tissue.

PMID- 22594491
TI  - Safety and tolerability of an SQ-standardized GRAss ALlergy immunotherapy tablet
      (GRAZAX(r)) in a real-life setting for three consecutive seasons - the GRAAL
      trial.
AB  - BACKGROUND AND OBJECTIVES: GRAZAX((r)) (Phleum Pratense, 75,000 SQ-T/2,800 BAU,
      ALK, Denmark), an SQ-standardized grass allergy sublingual immunotherapy tablet
      for the desensitization of grass pollen-induced rhinoconjunctivitis, has been
      developed to facilitate patient access to specific immunotherapy (SIT), while
      minimizing the risk of serious treatment-related adverse events. As a minimum
      duration of 3 years is recommended for SIT treatment, the GRAAL trial aimed to
      assess the safety profile of GRAZAX((r)) in real-world conditions during long
      term treatment of patients with grass pollen-induced allergic rhinoconjunctivitis
      (ARC). METHODS: A multicentre, prospective, open-label, observational trial was
      conducted over three consecutive grass pollen seasons from November 2007 to
      October 2010 in France. A total of 130 physicians included 628 patients with
      previously documented ARC. Patients received one tablet daily (no up-titration)
      for at least 4 months before the expected start of the pollen season (pre
      season), which was then maintained throughout the entire season (co-season). The
      primary endpoint was safety and tolerability (immediate, i.e. each year at first
      tablet administration, and long-term) after pre- and co-seasonal exposure to
      GRAZAX((r)). RESULTS: Patients were treated for an average of 5.5 months per
      year. After administration of the first tablet, immediate tolerable reactions
      (defined as benign, local, of short duration [<30 minutes] and not requiring any
      symptomatic treatment) were experienced by 54.6%, 38.4% and 33.6% of the patients
      during the first, second and third years of treatment, respectively. Immediate
      intolerable reactions (required study discontinuation, symptomatic medication or
      lasted >30 minutes) occurred in 14 patients (2.2%) during GRAZAX((r)) initiation,
      and one patient (0.3%) at treatment reintroduction during the second year.
      Adverse events considered to be related to GRAZAX((r)) were reported by 46.2%,
      14.4% and 1.8% of patients, during the first, second and third years of
      treatment, respectively. The most frequently reported adverse events were mild-to
      moderate local events (at the oral and pharyngeal mucosa levels). These symptoms
      mainly occurred within the first month of treatment initiation and subsequent
      tablet reintroduction. CONCLUSION: Daily administration of GRAZAX((r)) for three
      consecutive years was generally safe and well tolerated. An improvement in the
      incidence of adverse events related to treatment was observed at reintroduction
      of GRAZAX((r)) and during the course of treatment. TRIAL REGISTRATION:
      http://clinicaltrials.gov (NCT01433510).

PMID- 22594493
TI  - Modulation of DNA binding by reversible metal-controlled molecular
      reorganizations of scorpiand-like ligands.
AB  - DNA interaction with scorpiand azamacrocycles has been achieved through
      modulation of their binding affinities. Studies performed with different
      experimental techniques provided evidence that pH or metal-driven molecular
      reorganizations of these ligands regulate their ability to interact with calf
      thymus DNA (ctDNA) through an intercalative mode. Interestingly enough, metal
      driven molecular reorganizations serve to increase or decrease the biological
      activities of these compounds significantly.

PMID- 22594494
TI  - Annual economic impacts of seasonal influenza on US counties: spatial
      heterogeneity and patterns.
AB  - Economic impacts of seasonal influenza vary across US counties, but little
      estimation has been conducted at the county level. This research computed annual
      economic costs of seasonal influenza for 3143 US counties based on Census 2010,
      identified inherent spatial patterns, and investigated cost-benefits of
      vaccination strategies. The computing model modified existing methods for
      national level estimation, and further emphasized spatial variations between
      counties, in terms of population size, age structure, influenza activity, and
      income level. Upon such a model, four vaccination strategies that prioritize
      different types of counties were simulated and their net returns were examined.
      The results indicate that the annual economic costs of influenza varied from
      $13.9 thousand to $957.5 million across US counties, with a median of $2.47
      million. Prioritizing vaccines to counties with high influenza attack rates
      produces the lowest influenza cases and highest net returns. This research fills
      the current knowledge gap by downscaling the estimation to a county level, and
      adds spatial variability into studies of influenza economics and interventions.
      Compared to the national estimates, the presented statistics and maps will offer
      detailed guidance for local health agencies to fight against influenza.

PMID- 22594495
TI  - Rethinking molecular similarity: comparing compounds on the basis of biological
      activity.
AB  - Since the advent of high-throughput screening (HTS), there has been an urgent
      need for methods that facilitate the interrogation of large-scale chemical
      biology data to build a mode of action (MoA) hypothesis. This can be done either
      prior to the HTS by subset design of compounds with known MoA or post HTS by data
      annotation and mining. To enable this process, we developed a tool that compares
      compounds solely on the basis of their bioactivity: the chemical biological
      descriptor "high-throughput screening fingerprint" (HTS-FP). In the current
      embodiment, data are aggregated from 195 biochemical and cell-based assays
      developed at Novartis and can be used to identify bioactivity relationships among
      the in-house collection comprising ~1.5 million compounds. We demonstrate the
      value of the HTS-FP for virtual screening and in particular scaffold hopping. HTS
      FP outperforms state of the art methods in several aspects, retrieving bioactive
      compounds with remarkable chemical dissimilarity to a probe structure. We also
      apply HTS-FP for the design of screening subsets in HTS. Using retrospective
      data, we show that a biodiverse selection of plates performs significantly better
      than a chemically diverse selection of plates, both in terms of number of hits
      and diversity of chemotypes retrieved. This is also true in the case of hit
      expansion predictions using HTS-FP similarity. Sets of compounds clustered with
      HTS-FP are biologically meaningful, in the sense that these clusters enrich for
      genes and gene ontology (GO) terms, showing that compounds that are bioactively
      similar also tend to target proteins that operate together in the cell. HTS-FP
      are valuable not only because of their predictive power but mainly because they
      relate compounds solely on the basis of bioactivity, harnessing the accumulated
      knowledge of a high-throughput screening facility toward the understanding of how
      compounds interact with the proteome.

PMID- 22594496
TI  - Fabrication of flexible and vertical silicon nanowire electronics.
AB  - Vertical silicon nanowire (SiNW) array devices directly connected on both sides
      to metallic contacts were fabricated on various non-Si-based substrates (e.g.,
      glass, plastics, and metal foils) in order to fully exploit the nanomaterial
      properties for final applications. The devices were realized with uniform length
      Ag-assisted electroless etched SiNW arrays that were detached from their
      fabrication substrate, typically Si wafers, reattached to arbitrary substrates,
      and formed with metallic contacts on both sides of the NW array. Electrical
      characterization of the SiNW array devices exhibits good current-voltage
      characteristics consistent with the SiNW morphology.

PMID- 22594497
TI  - The importance of examining the proportion of circulating DNA originating from
      tumor, microenvironment and normal cells in colorectal cancer patients.
AB  - INTRODUCTION: The pressing need to determine the KRAS/BRAF mutational status for
      selecting patients with colorectal cancer (CRC) for anti-EGFR therapy provides a
      great opportunity to use circulating DNA (ctDNA) as a theranostic tool for
      personalized medicine. Better understanding of ctDNA origin (necrosis, apoptosis
      and active release) may increase the reliability of using abnormal ctDNA as
      biomarker. AREAS COVERED: The authors showed that examining the proportion of
      ctDNA originating from tumor, microenvironment and normal cells, through size
      distribution and mutation load may help to discriminate mechanisms of ctDNA
      release. EXPERT OPINION: Contrary to the literature, it was observed that tumor
      derived ctDNA was mostly shorter than 100 bp. Tumor-derived ctDNA from cancer
      patients exhibited a specific ctDNA size distribution profile and significantly
      higher ctDNA fragmentation than ctDNA from healthy individuals. Examination of
      the KRAS and BRAF mutational load in 48 mutated samples revealed very high
      variation ranging from 0.037 to 68.8%. This suggests either that tumor cells
      variably release ctDNA compared with tumor-associated stroma cells or normal
      cells, or that mutant ctDNA analysis may depend on tumor clonality. Detection of
      point mutation by quantifying the proportion of mutant ctDNA fragments provides a
      powerful tool for assessing the proportion of ctDNA from different origins.

PMID- 22594498
TI  - Conantokins derived from the Asprella clade impart conRl-B, an N-methyl d
      aspartate receptor antagonist with a unique selectivity profile for NR2B
      subunits.
AB  - Using molecular phylogeny has accelerated the discovery of peptidic ligands
      targeted to ion channels and receptors. One clade of venomous cone snails,
      Asprella, appears to be significantly enriched in conantokins, antagonists of N
      methyl d-aspartate receptors (NMDARs). Here, we describe the characterization of
      two novel conantokins from Conus rolani, including conantokin conRl-B that has
      shown an unprecedented selectivity for blocking NMDARs that contain NR2B
      subunits. ConRl-B shares only some sequence similarity with the most studied NR2B
      selective conantokin, conG. The divergence between conRl-B and conG in the second
      inter-Gla loop was used to design analogues for structure-activity studies; the
      presence of Pro10 was found to be key to the high potency of conRl-B for NR2B,
      whereas the epsilon-amino group of Lys8 contributed to discrimination in blocking
      NR2B- and NR2A-containing NMDARs. In contrast to previous findings for Tyr5
      substitutions in other conantokins, conRl-B[L5Y] showed potencies on the four NR2
      NMDA receptor subtypes that were similar to those of the native conRl-B. When
      delivered into the brain, conRl-B was active in suppressing seizures in the model
      of epilepsy in mice, consistent with NR2B-containing NMDA receptors being
      potential targets for antiepileptic drugs. Circular dichroism experiments
      confirmed that the helical conformation of conRl-B is stabilized by divalent
      metal ions. Given the clinical applications of NMDA antagonists, conRl-B provides
      a potentially important pharmacological tool for understanding the differential
      roles of NMDA receptor subtypes in the nervous system. This work shows the
      effectiveness of coupling molecular phylogeny, chemical synthesis, and
      pharmacology for discovering new bioactive natural products.

PMID- 22594499
TI  - Quantitative analysis of organelle distribution and dynamics in Physcomitrella
      patens protonemal cells.
AB  - BACKGROUND: In the last decade, the moss Physcomitrella patens has emerged as a
      powerful plant model system, amenable for genetic manipulations not possible in
      any other plant. This moss is particularly well suited for plant polarized cell
      growth studies, as in its protonemal phase, expansion is restricted to the tip of
      its cells. Based on pollen tube and root hair studies, it is well known that tip
      growth requires active secretion and high polarization of the cellular
      components. However, such information is still missing in Physcomitrella patens.
      To gain insight into the mechanisms underlying the participation of organelle
      organization in tip growth, it is essential to determine the distribution and the
      dynamics of the organelles in moss cells. RESULTS: We used fluorescent protein
      fusions to visualize and track Golgi dictyosomes, mitochondria, and peroxisomes
      in live protonemal cells. We also visualized and tracked chloroplasts based on
      chlorophyll auto-fluorescence. We showed that in protonemata all four organelles
      are distributed in a gradient from the tip of the apical cell to the base of the
      sub-apical cell. For example, the density of Golgi dictyosomes is 4.7 and 3.4
      times higher at the tip than at the base in caulonemata and chloronemata
      respectively. While Golgi stacks are concentrated at the extreme tip of the
      caulonemata, chloroplasts and peroxisomes are totally excluded. Interestingly,
      caulonemata, which grow faster than chloronemata, also contain significantly more
      Golgi dictyosomes and fewer chloroplasts than chloronemata. Moreover, the
      motility analysis revealed that organelles in protonemata move with low
      persistency and average instantaneous speeds ranging from 29 to 75 nm/s, which
      are at least three orders of magnitude slower than those of pollen tube or root
      hair organelles. CONCLUSIONS: To our knowledge, this study reports the first
      quantitative analysis of organelles in Physcomitrella patens and will make
      possible comparisons of the distribution and dynamics of organelles from
      different tip growing plant cells, thus enhancing our understanding of the
      mechanisms of plant polarized cell growth.

PMID- 22594500
TI  - Plasma profile of microRNA after supplementation with high doses of vitamin D3
      for 12 months.
AB  - BACKGROUND: Recently a large number of short non-coding-RNAs (microRNAs, (miRNA))
      have been identified. These miRNAs act as post-transcriptional regulators where
      they generally have an inhibitory function. miRNAs are present in all human
      cells, and they are also detected in serum or plasma. The miRNAs have a broad
      range of actions, and their biogenesis must therefore be under tight control. One
      putative regulator of miRNA biogenesis or miRNA level could be vitamin D, an
      ancient hormone with effects on cell growth and differentiation, apoptosis and
      the immune system. In our study miRNA were reversed transcribed in total RNA
      isolated from plasma and analyzed by quantitative real-time PCR (qPCR) using the
      miRCURY LNA Universal RT microRNA PCR system (Exiqon). In 10 pilot subjects 136
      miRNAs were detected in one or more plasma samples drawn at baseline and after 12
      months of vitamin D supplementation. The twelve miRNAs that showed the greatest
      change in expression in these pilots were further analyzed by RT-qPCR of RNA from
      baseline and 12 months plasma samples in 40 subjects given high dose vitamin D(3)
      (20.000-40.000 IU per week) and 37 subjects given placebo. RESULTS: At baseline
      there was a significant and positive correlation between serum 25-hydroxyvitamin
      D and miR-532-3p expression (r = 0.24, P = 0.04). The change in expression of miR
      221 from baseline to 12 months (ddCp value) was also significantly different
      between the vitamin D and placebo group (P =0.04), mainly due to a change in the
      placebo group. CONCLUSIONS: We have not been able to demonstrate a consistent
      effect of vitamin D supplementation on the expression profile of miRNA in plasma.
      However, further studies are needed as this approach might potentially throw
      light on unknown aspects of vitamin D physiology.

PMID- 22594501
TI  - Discovery of epilepsy susceptibility genes: implications for therapy development
      and pharmacogenomics.

PMID- 22594502
TI  - Genetic basis of susceptibility to drug-induced liver injury: what have we
      learned and where do we go from here?

PMID- 22594504
TI  - Identification of novel markers for 5-FU and FOLFOX toxicity.

PMID- 22594505
TI  - 5th Anniversary meeting of the European Research Network
      Pharmacogenetics/Pharmacogenomics. 8-9 December 2011, Utrecht, The Netherlands.

PMID- 22594506
TI  - Program in pharmacogenomics at the Ohio State University Medical Center.

PMID- 22594507
TI  - A clinically significant interaction between warfarin and simvastatin is unique
      to carriers of the CYP2C9*3 allele.
AB  - BACKGROUND: Simvastatin interacts with warfarin, but the strength of the
      interaction varies between individual patients, indicating a genetic
      predisposition. PATIENTS & METHODS: The influence of the CYP2C9*2 and CYP2C9*3
      polymorphisms on the interaction between simvastatin and warfarin was analyzed in
      data from 1132 patients. RESULTS: Simvastatin use reduced warfarin dose
      requirements by 29% in carriers of the CYP2C9*3 allele, compared with 5% in
      noncarriers. A regression model showed a significant influence of CYP2C9*3 on the
      drug-drug interaction, predicting a warfarin dose reduction of 25% in CYP2C9*3
      heterozygotes and 43% in CYP2C9*3 homozygotes. CONCLUSION: Our data indicate that
      the CYP2C9*3 polymorphism predisposes for a pharmacologic interaction between
      warfarin and simvastatin.

PMID- 22594508
TI  - Prognostic importance of VEGF-A haplotype combinations in a stage II colon cancer
      population.
AB  - AIM: To investigate the prognostic effect of three VEGF-A SNPs, -2578, -460 and
      405, as well as the corresponding haplotype combinations, in a unique population
      of stage II colon cancer patients. PATIENTS & METHODS: The study included all
      patients diagnosed with stage II colon cancer in Denmark in 2003 (698 patients).
      One paraffin-embedded tissue block from each patient was used for DNA extraction
      and analysis of the three VEGF SNPs. RESULTS: The homozygous genotype VEGF -2578
      AA had significant effect on time to tumor recurrence (hazard ratio [HR] = 2.01
      [95% CI: 1.13-3.56]; p = 0.02) as well as -460TT (HR = 0.50 [95% CI: 0.29-0.89];
      p = 0.02). Patients harboring the haplotype combinations ACG,CTC and ACG,ACG
      displayed a significantly shorter time to tumor recurrence in both univariate (HR
      = 1.87 [95% CI: 1.21-2.89]; p = 0.008) and multivariate analysis (HR = 1.76 [95%
      CI: 1.09-2.82]; p = 0.02). CONCLUSION: We found that the gene polymorphism in
      VEGF-A holds prognostic information and should be considered as a potential
      adjunct in identification of high-risk stage II colon cancer patients.

PMID- 22594509
TI  - Application of the F(ST) statistics to explore pharmacogenomic diversity in the
      Brazilian population.
AB  - BACKGROUND: New drug applications submitted to regulatory agencies in developing
      countries rarely include data from local clinical trials. We used the F(ST)
      statistics to explore the pharmacogenomic diversity of the Brazilian population
      and its potential implications in drug regulatory assessment and decisions.
      METHODS: The F(ST) analyses were based on data for 44 polymorphisms in 12
      pharmacogenes among 1034 healthy Brazilians, recruited in four different
      geographical regions and self-identified as branco (white) pardo (brown) or preto
      (black). Each region/color group comprised 83-89 individuals. The Utah residents
      of northern and western European ancestry and Yoruba people from Nigeria, Africa,
      cohorts of the HapMap project were used as proxies of the European and sub
      Saharan African ancestral roots of Brazilians, respectively. RESULTS: Allele
      specific F(ST) values for the overall Brazilian cohort revealed low genetic
      divergence between white and brown (F(ST) = 0.005 +/- 0.006, mean +/- standard
      deviation), white and black (0.013 +/- 0.017) and brown and black (0.004 +/-
      0.005) individuals. However, the distribution of F(ST) values for white vs brown
      (p < 0.0001, analysis of variance) and white vs black (p < 0.0001) differed
      significantly across the geographical regions. Considerably larger
      pharmacogenomic divergence was observed between black Brazilians and Yoruba
      people from Nigeria, Africa (F(ST) = 0.028 +/- 0.035) compared to white
      Brazilians vs Utah residents of northern and western European ancestry (0.007 +/-
      0.010). CONCLUSION: The present F(ST) analyses highlight the challenge faced by
      Brazilian regulatory agencies when assessing the relevance to Brazilians of
      pharmacogenomic data derived from foreign populations, with distinct
      biogeographical ancestries. This challenge is compounded by the heterogeneity of
      the Brazilian population with respect to the frequency distribution of
      pharmacogenomic polymorphisms across color categories and geographical regions.

PMID- 22594510
TI  - Association of genetic polymorphisms with response to bevacizumab for neovascular
      age-related macular degeneration in the Chinese population.
AB  - AIMS: To determine whether there is an association between CFH, ARMS2, HTRA1,
      VEGF, SERPING1 or C3 genotypes and patient response to treatment with
      intravitreal bevacizumab for neovascular age-related macular degeneration (AMD).
      MATERIALS & METHODS: This was a multicenter prospective study. One hundred and
      forty four patients with neovascular AMD treated with bevacizumab were recruited
      from 13 centers. Twelve SNPs were genotyped using Sequenom. Visual acuity score
      (VAS), central retinal thickness and maximum thickness of lesion were measured at
      each visit. RESULTS: For the CFH rs800292 polymorphism, mean VAS changes were
      4.4, 8.7 and 15.5 letters in the CC, CT and TT genotype carriers (p = 0.009). For
      ARMS2 rs10490924, mean VAS changes were 3.6, 12.1 and 9.6 letters for the TT, TG
      and GG genotypes (p = 0.001). For HTRA1 rs11200638, mean VAS changes were 3.6,
      12.3 and 9.6 letters for the AA, AG and GG genotypes (p < 0.001). CONCLUSION:
      CFH, ARMS2 and HTRA1 genotypes may influence patient response to treatment with
      intravitreal bevacizumab for neovascular AMD.

PMID- 22594511
TI  - Pharmacogenetics of EGFR in lung cancer: perspectives and clinical applications.
AB  - Lung cancer is a lethal disease, and most cases have already disseminated at the
      time of diagnosis. Driver mutations in the EGFR tyrosine kinase domain (mainly
      deletions in exon 19 and L858R mutation in exon 21) have been identified in lung
      adenocarcinomas, mostly in never smokers, at frequencies of 20-60%. The EGFR
      tyrosine kinase inhibitors (TKIs) gefitinib or erlotinib attain a response rate
      of 70% and progression-free survival of 9-13 months, although there are subgroups
      of patients with long-lasting remissions. No significant correlation between EGFR
      overexpression and response to treatment has been found, while controversial
      results have been reported regarding EGFR gene amplification. The pretreatment
      presence of the T790M mutation, initially identified as an acquired resistance
      mutation to treatment with EGFR TKIs, has also been reported and may indicate a
      genetically distinct disease. Finally, other genetic factors, such as mRNA
      expression of BRCA1 and components of the NF-kappaB pathway, can modulate
      response to EGFR TKIs in EGFR-mutated patients.

PMID- 22594512
TI  - Pharmacogenomics and public health: implementing 'populationalized' medicine.
AB  - Pharmacogenomics are frequently considered in personalized medicine to maximize
      therapeutic benefits and minimize adverse drug reactions. However, there is a
      movement towards applying this technology to populations, which may produce the
      same benefits, while saving already scarce health resources. We conducted a
      narrative literature review to examine how pharmacogenomics and public health can
      constructively intersect, particularly in resource-poor settings. We identified
      27 articles addressing the research question. Real and theoretical connections
      between public health and pharmacogenomics were presented in the areas of
      disease, drugs and public policy. Suggested points for consideration, such as
      educational efforts and cultural acceptability, were also provided. Including
      pharmacogenomics in public health can result in both health-related and economic
      benefits. Including pharmacogenomics in public health holds promise but deserves
      extensive consideration. To fully realize the benefits of this technology,
      support is needed from private, public and governmental sectors in order to
      ensure the appropriateness within a society.

PMID- 22594513
TI  - Pharmacogenomics of osteoporosis: a pathway approach.
AB  - Osteoporosis is frequent in postmenopausal women and old men. As with other
      prevalent disorders, it is the consequence of complex interactions between
      genetic and acquired factors. Candidate gene and genome-wide association studies
      have pointed to several genes as determinants of the risk of osteoporosis. Some
      of them were previously unsuspected and may help to find new therapeutic targets.
      Several drugs already available are very effective in increasing bone mass and
      decreasing fracture risk. However, not all patients respond properly and some of
      them suffer fragility fractures despite therapy. Investigators have tried to
      identify the genetic features influencing the response to antiosteoporotic
      therapy. In this article we will review recent data providing insight into new
      genes involved in osteoporosis and the pharmacogenetic data currently available.

PMID- 22594514
TI  - Pharmacogenetics of statins: achievements, whole-genome analyses and future
      perspectives.
AB  - Statins are the most commonly prescribed class of drug worldwide and therapy is
      highly effective in reducing low-density lipoprotein cholesterol levels and
      cardiovascular events. However, there is large variability in clinical response
      to statin treatment. Recent research provides evidence that genetic variation
      contributes to this variable response to statin treatment. Until recently,
      pharmacogenetic studies have used mainly candidate gene approaches to investigate
      these effects. Since candidate gene studies explain only a small part of the
      observed variation and results have often been inconsistent, genome-wide
      association (GWA) studies may be a better approach. In this paper the most
      important candidate gene studies and the first published GWA studies assessing
      statin response are discussed. Moreover, we describe the PHASE study, an EU
      funded GWA study that will investigate the genetic variation responsible for the
      variation in response to pravastatin in a large randomized clinical trial.

PMID- 22594516
TI  - Nitrous oxide (N2O) emission from aquaculture: a review.
AB  - Nitrous oxide (N(2)O) is an important greenhouse gas (GHG) which has a global
      warming potential 310 times that of carbon dioxide (CO(2)) over a hundred year
      lifespan. N(2)O is generated during microbial nitrification and denitrification,
      which are common in aquaculture systems. To date, few studies have been conducted
      to quantify N(2)O emission from aquaculture. Additionally, very little is known
      with respect to the microbial pathways through which N(2)O is formed in
      aquaculture systems. This review suggests that aquaculture can be an important
      anthropogenic source of N(2)O emission. The global N(2)O-N emission from
      aquaculture in 2009 is estimated to be 9.30 * 10(10) g, and will increase to 3.83
      * 10(11)g which could account for 5.72% of anthropogenic N(2)O-N emission by 2030
      if the aquaculture industry continues to increase at the present annual growth
      rate (about 7.10%). The possible mechanisms and various factors affecting N(2)O
      production are summarized, and two possible methods to minimize N(2)O emission,
      namely aquaponic and biofloc technology aquaculture, are also discussed. The
      paper concludes with future research directions.

PMID- 22594517
TI  - Evaluation of the sensitivity of two recently developed STR multiplexes for the
      analysis of chimerism after haematopoietic stem cell transplantation.
AB  - Forensic-oriented kits analysing short tandem repeat (STR) polymorphisms are
      widely used to determine the proportions of donor and recipient cells after
      haematopoietic stem cell transplantation. The sensitivity of this technology is
      crucial for the early detection of relapse and, in consequence, the adjustment of
      the treatment to enhance donor-origin haematopoiesis in transplant recipients.
      The objective of this study was to compare the performance of two recently
      developed STR multiplex kits, AmpFlSTR((r)) Identifiler((r)) Plus PCR
      Amplification Kit (Applied Biosystems) and InvestigatorTM IDplex((r)) (Qiagen),
      in the analysis of chimerism. Fifteen STR loci were amplified with both kits in
      26 peripheral blood samples of transplantated patients showing chimerism. Peak
      amplitude threshold, detection limit (%DL), per cent donor chimerism and efficacy
      of each multiplex and STR were determined, and the results with both kits were
      compared. The %DL and the estimated per cent donor chimerism were similar with
      both kits. On the other hand, Identifiler((r)) Plus kit allowed chimerism
      identification only in 24 (92%) of the 26 cases with chimerism detected by using
      the InvestigatorTM IDplex((r)) when only 'type 5' allelic constellations (i.e.
      without potential interference by stutter peaks) were taken into account.
      However, IDplex((r)) efficacy was somewhat lower than that of Identifiler Plus
      when only the most informative loci (D2S1338, D21S11, D18S51 and FGA) were
      considered. Therefore, although each system had some particular advantages and
      disadvantages, overall both STR multiplexes showed similar performance in
      qualitative and quantitative chimerism analysis.

PMID- 22594518
TI  - INFERCNMR: a 13C NMR interpretive library search system.
AB  - INFERCNMR is an automated (13)C NMR spectrum interpretation aid for use either as
      a stand-alone program or as a component of a comprehensive, computer-based system
      for the characterization of chemical structure. The program is an interpretive
      library search which requires a database of assigned (13)C NMR spectra. An
      interpretive library search does not require overall structural similarity
      between an unknown and a library entry in order to retrieve a substructure common
      to both. Input consists of the chemical shift and one-bond proton-carbon
      multiplicity of each signal in the spectrum, and the molecular formula of the
      unknown. Program output is one or more substructures predicted to be present in
      the unknown, each of which is assigned an estimated prediction accuracy.

PMID- 22594519
TI  - A deficiency in haem oxygenase-1 induces foetal growth restriction by placental
      vasculature defects.
AB  - Haem oxygenase-1 (HO-1), the rate-limiting enzyme in haem degradation, plays a
      role in angiogenesis and vasculogenesis and is highly expressed in the placenta.
      Deficiencies in HO-1 are associated with several pregnancy disorders, such as
      recurrent miscarriages and pre-eclampsia. The unique combination of tissue
      protective, smooth muscle relaxing and angiogenesis regulatory properties makes
      HO-1 a key player in the maintenance of a healthy pregnancy through a direct
      effect on placental structural and vascular development, thus affecting foetal
      development. CONCLUSION:   Therefore, we conclude that HO-1 plays an important
      role in placental vasculature development and a deficiency in HO-1 may contribute
      to pregnancy complications, such as pre-eclampsia, spontaneous abortions and
      premature births.

PMID- 22594520
TI  - Retropupillary iris claw intraocular lens for aphakia.
AB  - BACKGROUND: To assess outcomes of the iris claw intraocular lens implanted in the
      retropupillary position for correction of aphakia without adequate capsular
      support. DESIGN: Retrospective study of patients consulted at two private
      practices and a tertiary public hospital clinic in Brisbane, Queensland. SAMPLES:
      Thirty-two consecutive patients who underwent posterior chamber insertion of the
      iris claw intraocular lens alone or in combination with other procedure/s by the
      same consultant ophthalmologist (GL). METHODS: Lens power was calculated using an
      A-constant of 117.0. MAIN OUTCOME MEASURES: Clinical examination. RESULTS: Thirty
      four eyes in 32 patients (23 male, 9 female) were included in the study.
      Indications for surgery were pseudophakic bullous keratopathy (n = 14), aphakia
      from previous lens extraction/lensectomy (n = 9), subluxation of intraocular lens
      (n = 7), cataract extraction (n = 2), explantation of anterior chamber
      intraocular lens due to uveitis (n = 1) and for Baerveldt tube insertion (n = 1).
      Follow-up duration ranged from 1 to 68 months. Of the 26 eyes followed for at
      least 6 months, the final vision improved in 69% (n = 18), remained unchanged in
      8% (n = 2) and worsened in 23% (n = 6). Final visual acuity was 6/12 or better in
      58% (n = 15). Complications included iris trauma/defect (n = 8), pupil
      irregularity/ovalization (n = 6), microhyphaema (n = 2) and lens decentration (n
      = 2). CONCLUSION: Implantation of the iris claw intraocular lens in the
      retropupillary position is a useful technique for correction of aphakic eyes with
      sufficient iris support, avoiding the corneal complications of an anterior
      chamber intraocular lens and the surgical challenge of a sutured posterior
      chamber intraocular lens.

PMID- 22594521
TI  - Genomic in situ hybridization reveals both auto- and allopolyploid origins of
      different North and Central American hexaploid potato (Solanum sect. Petota)
      species.
AB  - Wild potato ( Solanum  L. sect.  Petota  Dumort.) species contain diploids (2n =
      2x = 24) to hexaploids (2n = 6x = 72). J.G. Hawkes classified all hexaploid
      Mexican species in series  Demissa  Bukasov and, according to a classic five
      genome hypothesis of M. Matsubayashi in 1991, all members of series Demissa are
      allopolyploids. We investigated the genome composition of members of Hawkes's
      series Demissa with genomic in situ hybridization (GISH), using labeled DNA of
      their putative progenitors having diploid AA, BB, or PP genome species or with
      DNA of tetraploid species having AABB or AAA(a)A(a) genomes. GISH analyses
      support  S. hougasii  Correll as an allopolyploid with one AA component genome
      and another BB component genome. Our results also indicate that the third genome
      of S. hougasii is more closely related to P or a P genome-related species. 
      Solanum demissum  Lindl., in contrast, has all three chromosome sets related to
      the basic A genome, similar to the GISH results of polyploid species of series 
      Acaulia  Juz. Our results support a more recent taxonomic division of the Mexican
      hexaploid species into two groups: the allopolyploid Iopetala group containing S.
      hougasii, and an autopolyploid Acaulia group containing S. demissum with South
      American species  S. acaule  Bitter and  S. albicans  (Ochoa) Ochoa.

PMID- 22594522
TI  - L-asparaginase-induced pancreatic injury is associated with an imbalance in
      plasma amino acid levels.
AB  - BACKGROUND: The use of L-asparaginase (ASNase) to modify amino acid metabolism is
      one of the most effective chemotherapeutic means of inducing remission in acute
      lymphoblastic leukemia (ALL). However, severe pancreatitis sometimes occurs in
      patients receiving ASNase, because of an unknown mechanism. OBJECTIVE: The
      purpose of the present study was to evaluate the relationship between ASNase
      induced pancreatic injury and plasma amino acid levels in patients undergoing
      ASNase therapy. METHODS: A total of 29 children aged 1-13.25 years (median age 4
      years; male : female ratio 19 : 10) with ALL, who received induction therapy
      according to the Tokyo Children's Cancer Study Group L04-16 protocol, were
      studied. Levels of plasma amino acids and serum rapid turnover proteins (RTPs),
      pancreatic enzymes, and pancreatic protease inhibitors were measured before and
      1, 2, 3, 4, 5, and 7 weeks after the first administration of ASNase. RESULTS:
      Plasma asparagine levels were significantly lower after the first injection of
      ASNase (p < 0.01) and had almost recovered 2 weeks after the last ASNase
      injection. At 4 weeks after the first ASNase injection, serum aspartic acid,
      trypsin, and pancreatic secretory trypsin inhibitor (PSTI) levels remained
      significantly higher than those before the first ASNase injection (p < 0.01), and
      serum levels of prealbumin and transferrin remained significantly lower than
      those before the first ASNase injection (p < 0.01). Plasma amino acid and serum
      RTP levels gradually normalized after the last ASNase injection. CONCLUSIONS:
      Levels of serum trypsin and PSTI were elevated during the 2 weeks after
      administration of ASNase, which suggested the presence of subclinical
      pancreatitis. This period is similar to the time period in the present study when
      the levels of plasma amino acids changed, thus suggesting that ASNase-induced
      pancreatic injury could be caused by the imbalance of plasma amino acid levels.

PMID- 22594523
TI  - Cost savings from assertive community treatment services in an era of declining
      psychiatric inpatient use.
AB  - OBJECTIVE: To assess, during a period of decreasing psychiatric inpatient
      utilization, cost savings from Assertive Community Treatment (ACT) programs for
      individuals with severe mental illnesses. DATA SOURCE: U.S. Department of
      Veterans Affairs' (VA) national administrative data for entrants into ACT
      programs. STUDY DESIGN: An observational study of the effects of ACT enrollment
      on mental health inpatient utilization and costs in the first 12 months following
      enrollment. ACT enrollees (N = 2010) were propensity score matched to ACT
      eligible non-enrollees (N = 4020). An instrumental variables generalized linear
      regression approach was used to estimate enrollment effects. RESULTS:
      Instrumental variables estimates indicate that between FY2001 and FY2004, entry
      into ACT resulted in a net increase of $4529 in VA costs. Trends in inpatient use
      among ACT program entrants suggest this effect remained stable after FY2004.
      However, eligibility for ACT declined 37 percent, because fewer patients met an
      eligibility standard based on high prior psychiatric inpatient use. CONCLUSIONS:
      Savings from ACT programs depend on new enrollees' intensity of psychiatric
      inpatient utilization prior to entering the ACT program. Although a program
      eligibility standard based on prior psychiatric inpatient use helped to sustain
      the savings from VA ACT programs, over time, it also resulted in an unintended
      narrowing of program eligibility.

PMID- 22594524
TI  - Deviation and failure of enhanced recovery after surgery following laparoscopic
      colorectal surgery: early prediction model.
AB  - AIM: Enhanced recovery after surgery (ERAS) programmes are well established, but
      deviation from the postoperative elements may result in delayed discharge. Early
      identification of such patients may allow remedial action to be taken. The aims
      of this study were to investigate factors associated with delayed discharge and
      to produce a predictive scoring system for ERAS failure. METHOD: A retrospective
      review was carried out of case notes of patients who underwent elective
      laparoscopic colorectal resection and ERAS at Yeovil District Hospital between
      2002 and 2009. Univariate and multivariate analyses were performed and binary
      logistic regression was used to model a predictive scoring system. RESULTS: In
      all, 385 patient records were reviewed with a median length of stay of 6 days;
      122 (31%) patients stayed longer than 1 week (delayed discharge) and 159 (41%)
      deviated in up to two postoperative ERAS factors. Patient demographic factors
      were not predictive of delayed discharge. Deviation from ERAS factors at the end
      of the first postoperative day, including continued intravenous fluid infusion,
      lack of functioning epidural, inability to mobilize, vomiting requiring
      nasogastric tube insertion and re-insertion of urinary catheter, were strongly
      associated with delayed discharge. A five-element predictive scoring system for
      ERAS failure and delayed discharge was formulated. CONCLUSION: Enhanced recovery
      failure and delayed discharge after laparoscopic colorectal surgery can be
      predicted by the early deviation from postoperative factors of an ERAS programme.

PMID- 22594525
TI  - Virtually nonexistent correlation between the OH stretching frequency and the
      instantaneous geometry in the short hydrogen bond of sodium hydrogen
      bis(sulfate): advanced chemometrics analysis.
AB  - We examined the correlation between the dynamically sampled anharmonic frequency
      of the OH stretching motion and the corresponding instantaneous geometric
      parameters associated with the structure of crystalline sodium hydrogen
      bis(sulfate), which is a benchmark system with an extremely short hydrogen bond.
      We analyzed the trajectory obtained by a conventional Car-Parrinello molecular
      dynamics simulation, followed by an a posteriori quantization of the proton
      motion. For statistical analysis we applied the established methodologies of
      multiple linear regression, principal component analysis, principal component
      regression, and Kohonen neural networks. No simple correlation scheme between the
      OH stretching frequency and any particular geometry parameter (or their
      combination) was found. In comparison to the established correlation schemes
      (e.g., Mikenda and Novak) that consider a series of systems, our study provides a
      complementary insight into the nature of hydrogen bonding of a single system, in
      the sense that it considers the important aspects of fluctuations of the
      environment and the resulting broadening of the OH stretching band, which cannot
      be adequately assessed by experiment. The absence of appreciable correlations
      gives strong evidence of the extreme complexity of short hydrogen bonding.

PMID- 22594526
TI  - Assessment of lymph node status in gallbladder cancer: location, number, or ratio
      of positive nodes.
AB  - A BACKGROUND: Assessment of lymph node status is a critical issue in the surgical
      management of gallbladder cancer. The aim of this study was to compare the
      anatomical location of positive nodes, number of positive nodes, and lymph node
      ratio (LNR) as prognostic predictors in gallbladder cancer. METHODS: We conducted
      a retrospective analysis of 135 patients with gallbladder cancer who underwent a
      radical resection with regional lymphadenectomy. A total of 2,245 regional lymph
      nodes were retrieved (median, 14 per patient). The location of positive nodes was
      classified according to the AJCC staging manual (7th edition). 'Optimal' cutoff
      values were determined for the number of positive nodes and LNR based on maximal
      chi(2) scores calculated with the Cox proportional hazards regression model.
      RESULTS: Lymph node metastasis was found histologically in 59 (44%) patients. The
      'optimal' cutoff values for the number of positive nodes and LNR were determined
      to be three nodes and 10%, respectively. Univariate analysis identified location
      of positive nodes (pN0, pN1, pN2; P<0.001), number of positive nodes (0, 1 to 3,
      >= 4; P <0.001), and LNR (0%, 0 to 10%, >10%; P<0.001) as significant prognostic
      factors. Multivariate analysis identified number of positive nodes as an
      independent prognostic factor ( P=0.004); however, location of positive nodes and
      LNR failed to remain as an independent variable. CONCLUSIONS: The number of
      positive lymph nodes better predicts patient outcome after resection than either
      the location of positive lymph nodes or LNR in gallbladder cancer. Dividing the
      number of positive lymph nodes into three categories (0, 1 to 3, or >= 4) is
      valid for stratifying patients based on the prognosis after resection.

PMID- 22594530
TI  - The three cornerstones of chemical biology: innovative probes, new discoveries,
      and enabling tools.

PMID- 22594531
TI  - Assigning renal allograft demise to antibodies: are we underplaying the role of T
      cells?

PMID- 22594532
TI  - Atomic ensemble and electronic effects in Ag-rich AgPd nanoalloy catalysts for
      oxygen reduction in alkaline media.
AB  - The ability to design and characterize uniform, bimetallic alloy nanoparticles,
      where the less active metal enhances the activity of the more active metal, would
      be of broad interest in catalysis. Herein, we demonstrate that simultaneous
      reduction of Ag and Pd precursors provides uniform, Ag-rich AgPd alloy
      nanoparticles (~5 nm) with high activities for the oxygen reduction reaction
      (ORR) in alkaline media. The particles are crystalline and uniformly alloyed, as
      shown by X-ray diffraction and probe corrected scanning transmission electron
      microscopy. The ORR mass activity per total metal was 60% higher for the AgPd(2)
      alloy relative to pure Pd. The mass activities were 2.7 and 3.2 times higher for
      Ag(9)Pd (340 mA/mg(metal)) and Ag(4)Pd (598 mA/mg(metal)), respectively, than
      those expected for a linear combination of mass activities of Ag (60 mA/mg(Ag))
      and Pd (799 mA/mg(Pd)) particles, based on rotating disk voltammetry. Moreover,
      these synergy factors reached 5-fold on a Pd mass basis. For silver-rich alloys
      (Ag(>=4)Pd), the particle surface is shown to contain single Pd atoms surrounded
      by Ag from cyclic voltammetry and CO stripping measurements. This morphology is
      favorable for the high activity through a combination of modified electronic
      structure, as shown by XPS, and ensemble effects, which facilitate the steps of
      oxygen bond breaking and desorption for the ORR. This concept of tuning the
      heteroatomic interactions on the surface of small nanoparticles with low
      concentrations of precious metals for high synergy in catalytic activity may be
      expected to be applicable to a wide variety of nanoalloys.

PMID- 22594533
TI  - Controlled synthesis of AlN/GaN multiple quantum well nanowire structures and
      their optical properties.
AB  - We report the controlled synthesis of AlN/GaN multi-quantum well (MQW) radial
      nanowire heterostructures by metal-organic chemical vapor deposition. The
      structure consists of a single-crystal GaN nanowire core and an epitaxially grown
      (AlN/GaN)(m) (m = 3, 13) MQW shell. Optical excitation of individual MQW
      nanowires yielded strong, blue-shifted photoluminescence in the range 340-360 nm,
      with respect to the GaN near band-edge emission at 368.8 nm. Cathodoluminescence
      analysis on the cross-sectional MQW nanowire samples showed that the blue-shifted
      ultraviolet luminescence originated from the GaN quantum wells, while the defect
      associated yellow luminescence was emitted from the GaN core. Computational
      simulation provided a quantitative analysis of the mini-band energies in the
      AlN/GaN superlattices and suggested the observed blue-shifted emission
      corresponds to the interband transitions between the second subbands of GaN, as a
      result of quantum confinement and strain effect in these AlN/GaN MQW nanowire
      structures.

PMID- 22594534
TI  - Editorial: vacuolar H(+)-ATPase: targeting a "housekeeping" enzyme for drug
      development.

PMID- 22594536
TI  - On learning to become a plant pathologist.

PMID- 22594535
TI  - Circulating nucleic acids in plasma and serum: an intriguing phenomenon.
AB  - The phenomenon of circulating nucleic acids in plasma and serum (CNAPS) has
      opened many new research lines, which may be framed within two areas of
      translational research: the development of new techniques for noninvasive
      prenatal diagnosis; and the study of the pathobiology of many diseases,
      particularly of cancer. The detection, quantization, and quality analysis of
      CNAPS have increasingly been found to be interesting and useful in the diagnosis
      and management of a number of pathologies, at least as complementary tools. The
      high potential value of CNAPS and the lack of knowledge about their origin and
      implications have aroused a great interest in many researchers, especially in the
      last two decades. In fact, in 1999, about 30 published studies focused on this
      issue, whereas in 2011 it was more than 100.

PMID- 22594537
TI  - From theory to 'measurement' in complex interventions: methodological lessons
      from the development of an e-health normalisation instrument.
AB  - BACKGROUND: Although empirical and theoretical understanding of processes of
      implementation in health care is advancing, translation of theory into structured
      measures that capture the complex interplay between interventions, individuals
      and context remain limited. This paper aimed to (1) describe the process and
      outcome of a project to develop a theory-based instrument for measuring
      implementation processes relating to e-health interventions; and (2) identify key
      issues and methodological challenges for advancing work in this field. METHODS: A
      30-item instrument (Technology Adoption Readiness Scale (TARS)) for measuring
      normalisation processes in the context of e-health service interventions was
      developed on the basis on Normalization Process Theory (NPT). NPT focuses on how
      new practices become routinely embedded within social contexts. The instrument
      was pre-tested in two health care settings in which e-health (electronic
      facilitation of healthcare decision-making and practice) was used by health care
      professionals. RESULTS: The developed instrument was pre-tested in two
      professional samples (N=46; N=231). Ratings of items representing normalisation
      'processes' were significantly related to staff members' perceptions of whether
      or not e-health had become 'routine'. Key methodological challenges are discussed
      in relation to: translating multi-component theoretical constructs into simple
      questions; developing and choosing appropriate outcome measures; conducting
      multiple-stakeholder assessments; instrument and question framing; and more
      general issues for instrument development in practice contexts. CONCLUSIONS: To
      develop theory-derived measures of implementation process for progressing
      research in this field, four key recommendations are made relating to (1) greater
      attention to underlying theoretical assumptions and extent of translation work
      required; (2) the need for appropriate but flexible approaches to outcomes
      measurement; (3) representation of multiple perspectives and collaborative nature
      of work; and (4) emphasis on generic measurement approaches that can be flexibly
      tailored to particular contexts of study.

PMID- 22594538
TI  - Novel therapeutic agents for cutaneous T-Cell lymphoma.
AB  - Mycosis fungoides (MF) and Sezary Syndrome (SS) represent the most common
      subtypes of primary Cutaneous T-cell lymphoma (CTCL). Patients with advanced MF
      and SS have a poor prognosis leading to an interest in the development of new
      therapies with targeted mechanisms of action and acceptable safety profiles. In
      this review we focus on such novel strategies that have changed the treatment
      paradigm of this rare malignancy.

PMID- 22594539
TI  - Design and preparation of porous polymers.

PMID- 22594541
TI  - Using ecosystem services to inform decisions on U.S. air quality standards.
AB  - The ecosystem services (ES) framework provides a link between changes in a
      natural system's structure and function and public welfare. This systematic
      integration of ecology and economics allows for more consistency and transparency
      in environmental decision making by enabling valuation of nature's goods and
      services in a manner that is understood by the public. This policy analysis (1)
      assesses the utility of the ES conceptual framework in the context of setting a
      secondary National Ambient Air Quality Standard (NAAQS), (2) describes how
      economic valuation was used to summarize changes in ES affected by NOx and SOx in
      the review, and (3) uses the secondary NOxSOx NAAQS review as a case study to
      highlight the advantages and challenges of quantifying air pollutant effects on
      ES in a decision making context. Using an ES framework can benefit the decision
      making process by accounting for environmental, ecological, and social elements
      in a holistic manner. As formal quantitative linkages are developed between
      ecosystem structure and function and ES, this framework will increasingly allow
      for a clearer, more transparent link between changes in air quality and public
      welfare.

PMID- 22594540
TI  - FcgammaRIIB-nt645+25A/G gene polymorphism and periodontitis in Japanese women
      with preeclampsia.
AB  - FcgammaRIIB contains a unique immunoreceptor tyrosine-based inhibition motif
      (ITIM) and functions as a negative feedback regulator of leucocyte activation and
      antibody production. We have previously reported FcgammaRIIB-nt645+25A/G gene
      polymorphism to be associated with prevalence and severity of periodontitis,
      FcgammaRIIB expression level on peripheral B lymphocytes and the serum IgG level
      against periodontopathic bacteria. Previous studies have reported maternal
      periodontal disease to be associated with an increased risk for preeclampsia.
      Therefore, FcgammaRIIB-nt645+25A/G gene polymorphism may be associated with
      preeclampsia by affecting immune response to periodontopathic bacteria in
      pregnant women. To elucidate whether FcgammaRIIB-nt645+25A/G gene polymorphism
      has associations with preeclampsia and/or periodontitis in pregnant Japanese
      women, a case-control study was carried out on women with preeclampsia (n = 13)
      and without preeclampsia (n = 106). Maternal periodontal parameters and bacterial
      data of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and
      Prevotella intermedia in subgingival plaque were collected within 5 days of
      delivery. FcgammaR genotypes of each woman were determined using the genomic DNA
      isolated from peripheral blood. Serum IgG levels specific for each bacteria were
      determined. There was a significant association between FcgammaRIIB-nt645+25A/G
      polymorphism and preeclampsia (P = 0.013). The frequency of the FcgammaRIIB
      nt645+25AA genotype was higher in the preeclampsia group compared with the
      nonpreeclampsia group (P = 0.007). The DNA level of A. actinomycetemcomitans from
      subgingival plaque was shown to be higher in the preeclampsia group (P = 0.017).
      In conclusion, maternal FcgammaRIIB-nt645+25A/G polymorphism and subgingival DNA
      level of A. actinomycetemcomitans were significantly associated with the
      prevalence of preeclampsia in a limited number of Japanese women independently
      with periodontal infection. Further investigations should be performed to confirm
      this association in a larger population and to determine the biological process
      of the association.

PMID- 22594542
TI  - Antimicrobial activity of some Clerodendrum species from Egypt.
AB  - Chloroformic and methanolic extracts of four Clerodendrum species cultivated in
      Egypt were screened for antimicrobial activities. Chloroformic extracts of the
      flowers of Clerodendrum chinense and Clerodendrum splendens were active against
      Plasmodium falciparum (IC50 < 10 ug mL(-1)). Chloroformic extracts of the stem
      and flowers of C. chinense were active against Trypanosoma cruzi (IC50 = 1.21 and
      1.12 ug mL(-1), respectively) with marginal cytotoxicity. Chloroformic extracts
      of the leaves of C. chinense and C. splendens showed promising activities against
      T. cruzi (IC50 = 3.39 and 1.98 ug mL(-1), respectively) without cytotoxic effect
      on a human cell line. None of the selected plants showed significant activity
      against Gram-negative or Gram-positive bacteria or Candida albicans.
      Verbascoside, a phenyl propanoid glycoside isolated from the leaves of C.
      chinense, showed marginal activity against T. cruzi. Rengyolone, a cyclohexyl
      ethanoid isolated from the leaves of C. chinense, showed a broad but not specific
      activity against the tested organisms.

PMID- 22594543
TI  - Ocular rigidity: biomechanical role, in vivo measurements and clinical
      significance.
AB  - Ocular rigidity (OR) refers to the relationship between pressure and volume
      changes in the eyeball. Since the description of the differential tonometry
      method for the calculation of an OR coefficient by Friedenwald, several other
      methodologies have been proposed to measure OR, including the anterior chamber
      manometry, axial length (AL) changes, measurement of pulse amplitude and fundus
      pulse, ultrasound elastography and evaluation of corneal hysteresis. However,
      most of these methodologies suffer from deficiencies, such as invasive nature,
      poor accuracy or reproducibility or technical complexity. Nevertheless, it is
      possible that OR affects the pathogenesis and clinical course of a variety of
      ocular conditions, including glaucoma, age-related macular degeneration,
      presbyopia, corneal changes following refractive surgery as well as the accuracy
      of IOP measurements by many tonometers. Thus, the future development of non
      invasive and easy-to-use methodologies for the accurate measurement of OR in the
      every-day practice would be clinically important.

PMID- 22594545
TI  - H Barry Collin Research Medal awarded to Professor Anthony J Adams.

PMID- 22594544
TI  - Research in diabetes and the eye: evolution or revolution?

PMID- 22594546
TI  - Alternative pathways in the development of diabetic retinopathy: the renin
      angiotensin and kallikrein-kinin systems.
AB  - Diabetic retinopathy is a common complication of both type 1 and type 2 diabetes
      and is the leading cause of blindness in people of working age. Current treatment
      strategies are mostly limited to laser photocoagulation, which restricts
      proliferative retinopathic changes but also causes irreversible damage to the
      retina. This review examines two important pathways involved in regulating
      vascular function and their role in the development of diabetic retinopathy. One,
      the renin-angiotensin system, is well known and has established angiogenic
      effects on the retina that increase in diabetic retinopathy. The other, the
      kallikrein-kinin system, has recently been found to be important in the
      development of diabetic retinal complications. This review describes the
      components of the two signalling networks, examines the current animal model
      studies investigating the role of these pathways in diabetic retinopathy and
      reviews the clinical studies that have been undertaken examining systemic
      inhibition of different points in these pathways. These systems are promising
      targets for therapies aimed at inhibiting the development of diabetic retinopathy
      and in the future, combination therapies that take advantage of both pathways
      might result in new treatment options for this debilitating complication of
      diabetes.

PMID- 22594547
TI  - Telemedicine and ocular health in diabetes mellitus.
AB  - Teleretinal/teleophthalmological programs that use existing health information
      technology infrastructure solutions for people with diabetes increase access to
      and adherence to appropriate eye care. Teleophthalmological studies indicate that
      the single act of patients viewing their own retinal images improves self
      management behaviour and clinical outcomes. In some settings this can be done at
      lower cost and with improved visual outcomes compared with standard eye care.
      Cost-effective and sustainable teleretinal surveillance for detection of diabetic
      retinopathy requires a combination of an inexpensive portable device for taking
      low light-level retinal images without the use of pharmacological dilation of the
      pupil and a computer-assisted methodology for rapidly detecting and diagnosing
      diabetic retinopathy. A more holistic telehealth-care paradigm augmented with the
      use of health information technology, medical devices, mobile phone and mobile
      health applications and software applications to improve health-care co
      ordination, self-care management and education can significantly impact a broad
      range of health outcomes, including prevention of diabetes-associated visual
      loss. This approach will require a collaborative, transformational, patient
      centred health-care program that integrates data from medical record systems with
      remote monitoring of data and a longitudinal health record. This includes data
      associated with social media applications and personal mobile health technology
      and should support continuous interactions between the patient, health-care team
      and the patient's social environment. Taken together, this system will deliver
      contextually and temporally relevant decision support to patients to facilitate
      their well-being and to reduce the risk of diabetic complications.

PMID- 22594548
TI  - Assessing corneal nerve structure and function in diabetic neuropathy.
AB  - The accurate detection and quantification of human diabetic peripheral neuropathy
      are important to define at-risk patients, anticipate deterioration and assess new
      therapies. Two emerging ophthalmic techniques, namely, corneal confocal
      microscopy and corneal aesthesiometry, demonstrate the ability to diagnose,
      quantify severity and assess therapeutic benefit in diabetic peripheral
      neuropathy. Corneal confocal microscopy allows quantification of corneal nerve
      morphology and non-contact corneal aesthesiometry assesses corneal sensitivity.
      The present review provides a detailed critique of the rationale, practical
      application in terms of the instruments used to capture images and the basis on
      which images are interpreted and analysed. We also critically evaluate how these
      two new non-invasive ophthalmic tests can be deployed to diagnose diabetic and
      other peripheral neuropathies.

PMID- 22594550
TI  - A two-compartment mixed-effects gamma regression model for quantifying between
      unit variability in length of stay among children admitted to intensive care.
AB  - OBJECTIVE: To quantify between-unit variability in mean length of stay (LoS)
      between intensive care units (ICUs) after adjusting for differences in case mix
      using a method that does not require arbitrary trimming of data. SETTING: An
      analysis of registry data from pediatric ICUs (PICUs) in Australia and New
      Zealand. STUDY DESIGN: The relationships between patient LoS and associated
      patient factors were modeled as a log-linear function of the covariates using two
      gamma distributions. The predicted distribution is estimated as a weighted
      average of the two distributions where the relative weighting is conditional on
      the patient's elective status. DATA COLLECTION: Data for 12,763 admissions
      submitted to the Australian and New Zealand Paediatric Intensive Care Registry
      from the eight dedicated PICUs in Australia and New Zealand in 2007 and 2008.
      PRINCIPAL FINDINGS: The two distributions of the mixture model accurately
      described the distribution of short- and long-stay patients in ICUs. After
      adjusting for patient case mix, several sites had a statistically significant
      effect on patient LoS. CONCLUSION: The two-compartment model characterizes ICU
      LoS for short- and long-stay patients more effectively than a single-compartment
      model. There is significant site-level variation in the LoS among children
      admitted to ICUs in Australia and New Zealand. Differences in the site-level
      variation between short- and long-stay patients indicate differences in discharge
      practice.

PMID- 22594551
TI  - Proton conduction in exchange membranes across multiple length scales.
AB  - Concerns over global climate change associated with fossil-fuel consumption
      continue to drive the development of electrochemical alternatives for energy
      technology. Proton exchange fuel cells are a particularly promising technology
      for stationary power generation, mobile electronics, and hybrid engines in
      automobiles. For these devices to work efficiently, direct electrical contacts
      between the anode and cathode must be avoided; hence, the separator material must
      be electronically insulating but highly proton conductive. As a result,
      researchers have examined a variety of polymer electrolyte materials for use as
      membranes in these systems.  In the optimization of the membrane, researchers are
      seeking high proton conductivity, low electronic conduction, and mechanical
      stability with the inclusion of water in the polymer matrix. A considerable
      number of potential polymer backbone and side chain combinations have been
      synthesized to meet these requirements, and computational studies can assist in
      the challenge of designing the next generation of technologically relevant
      membranes. Such studies can also be integrated in a feedback loop with experiment
      to improve fuel cell performance. However, to accurately simulate the currently
      favored class of membranes, perfluorosulfonic acid containing moieties, several
      difficulties must be addressed including a proper treatment of the proton-hopping
      mechanism through the membrane and the formation of nanophase-separated water
      networks.  We discuss our recent efforts to address these difficulties using
      methods that push the limits of computer simulation and expand on previous
      theoretical developments. We describe recent advances in the multistate empirical
      valence bond (MS-EVB) method that can probe proton diffusion at the nanometer
      length scale and accurately model the so-called Grotthuss shuttling mechanism for
      proton diffusion in water. Using both classical molecular dynamics and coarse
      grained descriptions that replace atomistic representations with collective
      coordinates, we investigated the proton conductivity of polymer membrane
      structure as a function of hydration level. Nanometer-sized water channels form
      torturous pathways that are traversed by the charges during fuel cell operation.
      Using a combination of coarse-grained membrane structure and novel multiscale
      methods, we demonstrate emerging approaches to treat proton motion at the
      mesoscale in these complex materials.

PMID- 22594552
TI  - Maternal nutrition among women from Sub-Saharan Africa, with a focus on Nigeria,
      and potential implications for pregnancy outcomes among immigrant populations in
      developed countries.
AB  - Pregnant women in countries of Sub-Saharan Africa (SSA) are at risk of poor
      nutritional status and adverse outcomes as a result of poverty, food insecurity,
      sub-optimal healthcare facilities, frequent infections and frequent pregnancies.
      Studies from Nigeria, for example, have revealed a high prevalence of both under-
      and over-nutrition, as well as nutrient deficiencies, including iron, folate,
      vitamin D and vitamin A. Subsequently, obstetric complications, including
      hypertension, anaemia, neural tube defects, night-blindness, low birth weight and
      maternal and perinatal mortality, are common. Migration patterns from SSA to the
      Western world are on the rise in recent years, with Nigerians now representing
      the most prevalent immigrant African population in many developed countries.
      However, the effect of immigration, if any, on the nutritional status and
      pregnancy outcomes of these women in their host countries has not yet been
      studied. Consequently, it is unknown to what extent the nutritional deficiencies
      and pregnancy complications occurring in Nigeria, and other countries of SSA,
      present in these women post-emigration. This may result in missed opportunities
      for appropriate antenatal care of a potential high-risk group in pregnancy. The
      present review discusses the literature regarding nutrition in pregnancy among
      SSA women, using Nigeria as an example, the common nutrition-related
      complications that arise and the subsequent obstetric outcomes. The concept of
      dietary acculturation among immigrant groups is also discussed and deficiencies
      in the literature regarding studies on the diets of pregnant immigrant women are
      highlighted.

PMID- 22594553
TI  - Transplant tourism or international transplant medicine? A case for making the
      distinction.
AB  - Transplant tourism is routinely denounced by influential voices such as the World
      Health Organization, the Declaration of Istanbul and the Madrid Resolution as an
      unethical solution to worldwide organ shortages. Instead, it is suggested that
      national deceased donor schemes and multinational organ-sharing programs are the
      only acceptable avenues for addressing the organ shortage crisis. The present
      demand for self-sufficiency in organ supply responds to risks such as poor
      clinical outcomes, and exploitation of the poor through the various commercial
      practices of transplant tourism. However, opponents of transplant tourism say
      little about what governments should do to ensure that their citizens have real
      and comprehensive access to all forms of transplantation. To address this complex
      question, we describe a current practice of international transplant medicine in
      Singapore. It addresses salient concerns with transplant tourism and supports the
      principle of national self-sufficiency in organ supply, even as its health care
      system thrives and expands comprehensive transplant services to its citizens by
      catering to international patients. We offer a critical appraisal of the
      Singaporean system, and some suggestions to minimize the risk of abuse by
      international patients or operatives of illegal organ markets.

PMID- 22594555
TI  - Fungi and fungicides the story of a nonconformist.

PMID- 22594554
TI  - VLS growth of alternating InAsP/InP heterostructure nanowires for multiple
      quantum-dot structures.
AB  - We investigated the Au-assisted growth of alternating InAsP/InP heterostructures
      in wurtzite InP nanowires on InP(111)B substrates for constructing multiple
      quantum-dot structures. Vertical InP nanowires without stacking faults were
      obtained at a high PH(3)/TMIn mole flow ratio of 300-1000. We found that the
      growth rate changed largely when approximately 40 min passed. Ten InAsP layers
      were inserted in the InP nanowire, and it was found that both the InP growth rate
      and the background As level increased after the As supply. We also grew the same
      structure using TBAs/TBP and could reduce the As level in the InP segments. A
      simulation using a finite-difference time-domain method suggests that the
      nanowire growth was dominated by the diffusion of the reaction species with long
      residence time on the surface. For TBAs/TBP, when the source gases were changed,
      the formed surface species showed a short diffusion length so as to reduce the As
      background after the InAsP growth.

PMID- 22594556
TI  - Secondary diabetes associated with 5-fluorouracil-based chemotherapy regimens in
      non-diabetic patients with colorectal cancer: results from a single-centre cohort
      study.
AB  - AIM: The aim of the study was to analyse the prevalence and characteristics of
      secondary diabetes induced by 5-fluorouracil (5-FU) based chemotherapy in non
      diabetic patients with colorectal cancer (CRC). METHOD: A total of 422
      consecutive CRC patients who received 5-FU-based chemotherapy were
      retrospectively analysed. Fasting plasma glucose (FPG) levels were determined
      before each cycle of chemotherapy during active treatment and regular follow-up.
      The prevalence and characteristics of secondary hyperglycaemia were investigated,
      with special focus on the clinical outcome. RESULTS: Among the 422 CRC patients,
      60 had pre-existing hyperglycaemia. In the remaining 362 with normal FPG levels
      before chemotherapy, 42 (11.6%) and 41 (11.3%) patients developed diabetes and
      impaired fasting glucose during the study period. Among the 42 secondary diabetic
      patients, 22 (52.4%) received anti-diabetes drug therapy, in 7 (16.7%) cases the
      FPG level returned to normal without any active intervention, and 13 (30.9%)
      cases received diet control and physiotherapy. Thirty-one (8.6%) patients
      developed diabetes. Based on the Common Terminology Criteria for Adverse Events,
      an adverse event over Grade 3 occurred in seven cases during follow-up. Diabetes
      related adverse events had a serious negative impact on chemotherapy in six
      cases. Diabetes-related death occurred in three patients. CONCLUSIONS: Secondary
      diabetes associated with 5-FU-based chemotherapy occurs in around 10% of CRC
      patients, with a significant negative impact on treatment and clinical outcome. 5
      FU-related diabetes should be regarded as a common side effect of 5-FU treatment.

PMID- 22594558
TI  - Cost effectiveness of interferon-gamma release assay for school-based
      tuberculosis screening.
AB  - PURPOSE: To assess the cost effectiveness of school-based tuberculosis (TB)
      screening using QuantiFERON(r)-TB Gold In-Tube (QFT) versus the tuberculin skin
      test (TST) and chest x-ray examination (CXR). METHODS: We constructed Markov
      models of first-year high-school and university students, using a societal
      perspective, and followed them up until the age of 80 years. Three strategies
      (QFT, TST, and CXR) were modeled. All costs and clinical benefits were discounted
      at a fixed annual rate of 3%. RESULTS: In the base-case analyses of 16-year-old
      high-school students and 19-year-old university students, the QFT strategy
      yielded the greatest benefits at the lowest cost [in year 2009 values] (16-year
      olds: $US627.89, 29.69835 quality-adjusted life-years [QALYs]; 19-year-olds:
      $US646.04, 29.15361 QALYs), compared with the TST strategy (16-year-olds:
      $US943.50, 29.69767 QALYs; 19-year-olds: $US998.62, 29.15288 QALYs) and the CXR
      strategy (16-year-olds: $US7286.24, 29.69532 QALYs; 19-year-olds: $US7305.19,
      29.14911 QALYs). On one-way sensitivity analyses, the bacillus Calmette-Guerin
      (BCG) vaccination rate was not sensitive to the TST strategy. On probabilistic
      sensitivity analysis, the QFT strategy was the most cost effective, with a
      willingness-to-pay level of $US50 000/QALY gained. CONCLUSION: The QFT strategy
      provided the greatest benefits at the lowest cost for school-based TB screening.
      There appears to be little role for TST or CXR in screening of school
      populations. Current practices using either TST or CXR screening should be
      reconsidered on the basis of cost effectiveness.

PMID- 22594557
TI  - Comprehensive geriatric assessment for older women with early breast cancer - a
      systematic review of literature.
AB  - BACKGROUND: The Comprehensive Geriatric Assessment (CGA) is an analytical tool
      increasingly implemented in clinical practice. Breast cancer is primarily a
      disease of older people; however, most evidence-based research is aimed at
      younger patients. METHODS: A systematic review of literature was carried out to
      assess the use of CGA in older breast cancer patients for clinical decision
      making. The PubMed, Embase and Cochrane databases were searched. RESULTS: A total
      of nine useful full text article results were found. Only five of these were
      exclusively concerned with early breast cancer; thus, studies involving a variety
      of cancer types, stages and treatments were accepted, as long as they included
      early breast cancer.The results comprised a series of low sources of evidence.
      However, all results shared a common theme: the CGA has a use in determining
      patient suitability for different types of cancer treatment and subsequently
      maximizing the patient's quality of life. CONCLUSIONS: There is not yet
      sufficient high level evidence to instate CGA guidelines as a mandatory practice
      in the management of breast cancer, due to the heterogeneity of available
      studies. More studies need to be conducted to cement current work on the benefits
      of the CGA. An area of particular interest is with regard to treatment options,
      especially surgery and chemotherapy, and identifying patients who may be suitable
      for these treatments.

PMID- 22594559
TI  - Sphingosine kinase-1 inhibition sensitizes curcumin-induced growth inhibition and
      apoptosis in ovarian cancer cells.
AB  - Recent published studies suggest that increasing levels of ceramides enhance the
      chemo-sensitivity of curcumin. Using in vitro approaches, we analyzed the impact
      of sphingosine kinase-1 (SphK-1) inhibition on ceramide production, and evaluated
      SphK1 inhibitor II (SKI-II) as a potential curcumin chemo-sensitizer in ovarian
      cancer cells. We found that SphK1 is overexpressed in ovarian cancer patients'
      tumor tissues and in cultured ovarian cancer cell lines. Inhibition of SphK1 by
      SKI-II or by RNA interference (RNAi) knockdown dramatically enhanced curcumin
      induced apoptosis and growth inhibition in ovarian cancer cells. SKI-II
      facilitated curcumin-induced ceramide production, p38 activation and Akt
      inhibition. Inhibition of p38 by the pharmacological inhibitor (SB 203580), a
      dominant-negative expression vector, or by RNAi diminished curcumin and SKI-II co
      administration-induced ovarian cancer cell apoptosis. In addition, restoring Akt
      activation introducing a constitutively active Akt, or inhibiting ceramide
      production by fumonisin B1 also inhibited the curcumin plus SKI-II co
      administration-induced in vitro anti-ovarian cancer effect, suggesting that
      ceramide accumulation, p38 activation and Akt inhibition are downstream
      effectors. Our findings suggest that low, well-tolerated doses of SKI-II may
      offer significant improvement to the clinical curcumin treatment of ovarian
      cancer.

PMID- 22594560
TI  - Absence of Helicobacter pylori high tetracycline resistant 16S rDNA AGA926-928TTC
      genotype in gastric biopsy specimens from dyspeptic patients of a city in the
      interior of Sao Paulo, Brazil.
AB  - BACKGROUND: Treatment effectiveness of Helicobacter pylori varies regionally and
      is decreasing worldwide, principally as a result of antibiotic resistant
      bacterium. Tetracycline is generally included in second line H. pylori
      eradication regimens. In Brazil, a high level of tetracycline resistance (TetR)
      is mainly associated with AGA926-928TTC 16 S rDNA nucleotide substitutions. As H.
      pylori culture is fastidious, we investigated the primary occurrence of H. pylori
      16 S rDNA high level TetR genotype using a molecular approach directly on gastric
      biopsies of dyspeptic patients attending consecutively at Hospital das Clinicas
      of Marilia, Sao Paulo, Brazil. METHODS: Gastric biopsy specimens of 68 peptic
      ulcer disease (PUD) and 327 chronic gastritis (CG) patients with a positive
      histological diagnosis of H. pylori were investigated for TetR 16 S rDNA genotype
      through a molecular assay based on amplification of a 16 S rDNA 545 bp fragment
      by polymerase chain reaction and HinfI restriction fragment length polymorphism
      (PCR/RFLP). Through this assay, AGA926-928TTC 16 S rDNA TetR genotype resulted in
      a three DNA fragment restriction pattern (281, 227 and 37 bp) and its absence
      originated two DNA fragments (264 and 281 bp) due to a 16 S rDNA conserved Hinf I
      restriction site. RESULTS: The 545 bp 16 S rDNA PCR fragment was amplified from
      90% of gastric biopsies from histological H. pylori positive patients. HinfI RFLP
      revealed absence of the AGA926-928TTC H. pylori genotype and PCR products of two
      patients showed absence of the conserved 16 S rDNA HinfI restriction site. BLASTN
      sequence analysis of four amplicons (two conserved and two with an unpredicted
      HinfI restriction pattern) revealed a 99% homology to H. pylori 16 S rDNA from
      African, North and South American bacterial isolates. A nucleotide substitution
      abolished the conserved HinfI restriction site in the two PCR fragments with
      unpredicted HinfI RFLP, resulting in an EcoRI restriction site. CONCLUSIONS: H.
      pylori AGA926-928TTC 16 S rDNA gene substitutions were not found in our
      population. More research is required to investigate if H. pylori TetR has a
      different genetic background in our region and if the nucleotide substitutions of
      the uncultured H. pylori 16 S rRNA partial sequences have biological
      significance.

PMID- 22594562
TI  - Assessment of diabetic retinopathy by measuring retina-specific mRNA in blood.
AB  - INTRODUCTION: Diabetic retinopathy (DR) is the leading cause of blindness in
      adults. Early detection and treatment of DR has been shown to reduce the risk of
      visual loss by as much as 90%. At present, there are no blood tests to detect DR.
      Previous studies have demonstrated the presence of nucleic acids in blood and
      raised levels of these markers have been reported in many conditions. The aim of
      this study was to evaluate the circulating levels of retina-specific mRNA in the
      assessment of DR. AREAS COVERED: Blood samples were taken into PAXgene Blood RNA
      tubes from 89 diabetic patients and 19 healthy individuals. A reverse
      transcription quantitative real-time PCR assay was used to measure circulating
      levels of mRNA for rhodopsin (Rho), retinal amine oxidase (RAO) and
      phosphodiesterase 6C (PDE6C). The results were normalized against mRNA for beta
      actin and total RNA. While mRNA for Rho, RAO and beta-actin were detected in 100%
      of the subjects, PDE6C mRNA was only found in 60% of the individuals and
      melanopsin mRNA was not detected. When diabetic subjects were divided according
      to their DR status, significant differences were observed for Rho and RAO-Rho
      increased while RAO tended to decrease. The area under the curve ROC for Rho and
      Rho/RAO ratio to differentiate mild or no DR from significant DR (pre
      proliferative and proliferative stages) were 0.756 and 0.823, respectively.
      EXPERT OPINION: These findings suggest that circulating mRNA may be useful in
      assessing DR.

PMID- 22594561
TI  - Iridium-catalyzed [2 + 2 + 2] cycloaddition of alpha,omega-diynes with nitriles.
AB  - [Ir(cod)Cl](2)/DPPF or BINAP efficiently catalyzed the cycloaddition of
      alpha,omega-diynes with nitriles to give pyridines. The reaction can accommodate
      a very wide range of nitriles. Both aliphatic and aromatic nitriles smoothly
      reacted with alpha,omega-diynes to give pyridines. Ten equivalents of unactivated
      aliphatic nitrile were enough to give the product in high yield. Aliphatic
      nitriles bearing an acetal or amino moiety could be used for the reaction. The
      highly regioselective cycloaddition of unsymmetrical diyne bearing two different
      internal alkyne moieties was achieved. The observed regioselectivity could be
      reasonably explained by considering the different reactivities of the alpha
      position in iridacyclopentadiene. Regioselective cycloaddition was successfully
      applied to the synthesis of terpyridine and quinquepyridine. This chemistry was
      extended to a new and efficient synthesis of oligoheteroarenes. Five aromatic or
      heteroaromatic rings were connected in a single operation. [Ir(cod)Cl](2)/chiral
      diphosphine catalyst can be applied to enantioselective synthesis. Kinetic
      resolution of the racemic secondary benzyl nitrile catalyzed by
      [Ir(cod)Cl](2)/SEGPHOS gave a central carbon chiral pyridine in 80% ee. The
      mechanism was analyzed on the basis of the B3LYP level of density functional
      calculations.

PMID- 22594563
TI  - Imide photodissociation investigated by X-ray absorption spectroscopy.
AB  - X-ray absorption spectroscopy is used to investigate the photodissociation of the
      imides PMDI (pyromellitic diimide) and SSMCC (sulfosuccinimidyl 4-(N
      maleimidomethyl) cyclohexane-1-carboxylate). PMDI contains only one type of
      imide, and its photodissociation can be explained by a simple conversion from
      imide to a mix of imine and nitrile after desorption of the oxygens from the
      imide. SSMCC contains two different imides. One reacts like PMDI, the other in a
      more complex multistep process. Eventually, N(2) is formed in the bulk of the
      sample at high radiation density. The sequence of reactions is inferred from the
      pi* peaks in total electron yield and fluorescence yield absorption spectra at
      the N 1s and O 1s edges. First-order rate equations are used to model the
      evolution of the peak areas versus radiation dose.

PMID- 22594564
TI  - In vitro drug metabolism of green tea catechins in human, monkey, dog, rat and
      mouse hepatocytes.
AB  - The metabolic fate of green tea catechins [(-)-epicatechin ((-)-EC), (-)
      epicatechin-3-gallate (ECG) (-)- epigallocatechin (EGC) and (-)-epigallocatechin
      3-gallate (EGCG)] in cryopreserved human, monkey, dog, rat and mouse hepatocytes
      was studied. Methylation, glucuronidation, sulfation and isomerization pathways
      of (-)-EC in all five species were found. Methylation, glucuronidation,
      sulfation, hydrolysis, isomerization and glucosidation pathways of ECG were
      found. Species differences in metabolism of (-)-EC or ECG were observed.
      Surprisingly, no metabolites of EGC or EGCG were detected, but chemical oxidation
      and polymerization were observed under these experimental conditions. It appeared
      that enzymatic reactions and chemical reactions were differentiated by an
      additional hydroxyl group on the B-ring between (-)-EC/ECG and EGC/EGCG. For (-)
      EC, thirty-five metabolites including isomerized (M6. M10 and M25),
      glucuronidated (M3, M5 and M11), sulfated (M7, M15, M16, M18, M20, M23, M26),
      methylated (M2, M9, M12, M17, M19, M21, M27, M30, M32), glucuronated/methylated
      (M4, M8, M13, M14), sulfated/methylated (M22, M24, M28, M29, M31, M33, M34, M35)
      and diglucuronidate (M1), were detected and characterized. M11, M18, M19 and M23
      were major metabolites in human hepatocytes; M11, M26 and M31 were major
      metabolites in monkey hepatocytes; M10, M20, M22, M26 and M31 were major
      metabolites in dog hepatocytes; M5, M6 and M10 were major metabolites in rat
      hepatocytes; and M5, M6 and M13 were major metabolites in mouse hepatocytes. For
      ECG, twelve metabolites including isomerized (M1), hydrolyzed (M3), glucosidated
      (M2), glucuronidated (M4 and M6), sulfated (M9, M11 and M12), methylated (M7),
      sulfated/glucuronidated/methylated (M8 and M10) and diglucuronidated (M5), were
      detected and characterized. M4, M11 and M12 were major metabolites in human
      hepatocytes; M11 and M12 were major metabolites in monkey hepatocytes; M3 and M11
      were major metabolites in dog hepatocytes; M4, M6 and M11 were major metabolites
      in rat hepatocytes, and M3 was a major metabolite in mouse hepatocytes. The
      experimental results have demonstrated that fate of catechins in in vitro
      hepatocytes depends on metabolism and chemical stability. In certain experimental
      conditions, the chemical reaction may become a dominant pathway.

PMID- 22594565
TI  - Single-dose pharmacokinetics and tolerability of oral delta-9-
      tetrahydrocannabinol in patients with amyotrophic lateral sclerosis.
AB  - BACKGROUND: Cannabinoids exert neuroprotective and symptomatic effects in
      amyotrophic lateral sclerosis (ALS). We assessed the pharmacokinetics (PK) and
      tolerability of delta-9-tetrahydrocannabinol (THC) in ALS patients. METHODS: Nine
      patients received THC single oral doses of 5mg and 10mg, separated by a wash-out
      period of two weeks. Blood samples for the determination of THC, 11-nor-9-carboxy
      THC (THC-COOH) and hydroxy-THC (THC-OH) were taken up to 8 hours after intake.
      Adverse events were assessed by visual analogue scales (VAS). Plasma
      concentrations of the active metabolite THC-OH were submitted to sequential
      pharmacokinetic-pharmacodynamic population modeling on individual heart rate as a
      proxy for THC's cardiovasculatory effects. RESULTS: Drowsiness, euphoria,
      orthostasis, sleepiness, vertigo and weakness were significantly more frequent in
      patients receiving 10mg compared to 5 mg THC. A marked interindividual
      variability was found for the absorption of oral THC (84%) and elimination of THC
      COOH (45%). PK data did not support any clinically relevant deviation from linear
      PK in the investigated range of concentrations. Plasma concentrations of THC-OH
      were positively correlated with the individual heart rate. An E(max-model) was
      successfully fitted to individual heart rate, with a THC-OH plasma concentration
      of 3.2 x 10(-4) MUmol/L for EC(50) and an E(max) of 93 bpm for heart rate.
      CONCLUSIONS: The higher 10mg dose of THC was dose-limiting in patients with ALS.
      High interindividual PK variability requires individuell titration of THC for
      potential therapeutic use in patients with ALS.

PMID- 22594566
TI  - Limitations of S-warfarin truncated area under the concentration-time curve to
      predict cytochrome P450 2c9 activity.
AB  - OBJECTIVE: Phenotyping cytochrome P450 (CYP) 2C9 activity with S-warfarin
      requires extensive blood sampling to characterize area under the concentration
      time curve (AUC). This retrospective data analysis was conducted to determine if
      truncated S-warfarin AUCs can be used to measure CYP2C9 activity. METHODS: S
      warfarin plasma concentrations were obtained from healthy adults (n = 84)
      genotyped as CYP2C9 extensive metabolizers (EMs) from 6 published studies.
      Subjects received a single 10 mg oral warfarin dose during baseline and treatment
      conditions. AUC zero to infinity (AUCINF) and truncated AUCs at 48 h (AUC(48)),
      at 72 h (AUC(72)) and at 96 h (AUC(96)) were determined by noncompartmental
      analysis. Equivalence was determined via least squares geometric mean ratios (LS
      GMRs) with 90% confidence intervals (CI) within 0.8-1.25. RESULTS: A lack of
      equivalence was observed for AUC(48) and AUC(72) compared to AUC(INF) during
      baseline conditions in all evaluated studies and during treatment conditions in 5
      of 6 studies. Equivalence was observed for AUC(96) compared to AUC(INF) during
      all baseline and treatment conditions. Results were consistent across all
      evaluated AUCs between baseline and treatment without a CYP2C9-mediated drug-drug
      interaction and during induction with an oral contraceptive. During inhibition
      with fluvastatin, a lack of equivalence was observed with AUC(INF)(LS-GMR [90%CI]
      = 1.25 [1.16-1.34]) and AUC(96) (1.2 [1.13=1.27]). In contrast, equivalence was
      observed for AUC(48)(1.15 [1.08-1.22]) and AUC(72) (1.18 [1.11-1.24]).
      CONCLUSIONS: S-warfarin truncated AUC(48) and AUC(72) poorly characterize
      AUC(INF) and are unable to detect weak CYP2C9 inhibition with fluvastatin. S
      warfarin phenotyping parameters need to ensure blood sampling of at least 96 h to
      characterize AUC and thus CYP2C9 activity.

PMID- 22594567
TI  - The pharmacokinetics and metabolism study of sodium 7,4' -oxo-acetic acid
      daidzein in rat.
AB  - OBJECT: To Study the pharmacokinetics and metabolism of Sodium 7,4' -oxo-acetic
      acid daidzein in rat. METHOD: Sodium 7,4' -oxo-acetic acid daidzein was
      determined by reversed-phase HPLC (column: German CenturySIL BDS C18 5 MUm
      silica, 200 mm x 4.6 mm i.d; fluid: methanol-water-85% phosphoric
      acid(57:43:0.05, v/v/v)), with sodium benzoic acid as an internal standard.
      Biological samples were extracted with acetonitrile. RESULTS: The calibration
      curve was linear over the range of 1.0-1000 MUg/ml in rat plasma, urine and
      feces. The average extraction recoveries were 73.3% (plasma), 73.9% (urine) and
      83.7% (feces) respectively and the intra-day and inter-day precisions were less
      than 8.34%. The assay was applied to the analysis of samples from a
      pharmacokinetic study. The absolute bioavailability of oral administration was
      3.07%. DZ I original compound determined in 6h urine was 32.32%, in 24h urine was
      32.71%, in 24h feces was 22.96%.

PMID- 22594568
TI  - The Lown Symposium: The Field of DNA Minor Groove Binders Celebrates the Career
      of Professor J. William Lown.
AB  - Abstract   A symposium co-organized by Professor William H. Gmeiner of Wake
      Forest University School of Medicine and Professor Moses Lee of Furman University
      was held March 30 and 31, 2001 on the campus of Wake Forest University School of
      Medicine. The Symposium was attended by many distinguished colleagues, friends
      and co-workers of Professor Lown who share his enthusiasm and passion for
      targeting DNA for treatment of human disease. The Symposium honored the formal
      "retirement" of Professor Lown who continues his active pursuit of scholarly
      activities and advancement of knowledge in a wide variety of intellectual
      interests.

PMID- 22594569
TI  - The genetics of the alternative pathway of complement in the pathogenesis of
      HELLP syndrome.
AB  - OBJECTIVE: Recent preliminary evidence suggests that gene mutations in the
      alternative pathway of complement may play a crucial role in the pathogenesis of
      HELLP syndrome. To verify this hypothesis, a consecutive series of women who
      developed the syndrome was screened for variants in alternative pathway genes.
      METHODS: The coding sequences and intron-exon boundaries of the complement factor
      H (CFH), complement factor I (CFI), Membrane Cofactor Protein (MCP), complement
      factor B (CFB) and C3 were sequenced in 33 women with a diagnosis of HELLP
      syndrome. RESULTS: Three patients carried heterozygotic variants - two in CFI and
      one in MCP. One of the two CFI mutations, was previously described as an
      unremarkable polymorphism. Conversely, computational analyses for the remaining
      two cases suggest that they may have a functional impact. CONCLUSIONS: The
      present study confirms that the alternative pathway of complement may play a role
      in the pathogenesis of HELLP syndrome. However, its overall contribution to the
      determinism of the syndrome is less relevant than initially reported.

PMID- 22594570
TI  - Inflammatory pseudotumor arising from the right ventricular outflow tract causing
      pulmonary stenosis.
AB  - Inflammatory pseudotumor (also known as inflammatory myofibroblastic tumor) is an
      uncommon spindle cell lesion that was initially recognized in the lung and is now
      known to occur in virtually every major organ of the body. We report a case of a
      seven-year-old male who had an inflammatory pseudotumor of the right ventricular
      outflow tract involving the pulmonary valve causing pulmonary stenosis.

PMID- 22594571
TI  - A new triterpenoid saponin from Glinus oppositifolius with alpha-glucosidase
      inhibitory activity.
AB  - Evaluation of alpha-glucosidase inhibitory activity led to the isolation of six
      triterpene saponins from the aerial parts of Glinus oppositifolius including one
      new and five known constituents. The structure of the new saponin, glinoside C
      (1), was established as 16-O-(beta-D-glucopyranosyl)
      3beta,12beta,16beta,21alpha,22-pentahydroxy hopane by extensive use of 1-D, 2-D
      NMR and mass spectral techniques. The other constituents identified were 3-O
      (beta-D-xylopyranosyl)-spergulagenin A (2), spergulacin (3), spergulin A (4),
      spergulacin A (5) and spergulin B (6). Compound 1 exhibited the greatest
      inhibition of the enzyme with IC50 of 127 +/- 30 uM. Kinetics study for the
      compound 1 demonstrated mixed type of inhibition (Ki = 157.9 uM).

PMID- 22594572
TI  - Prenatal and neonatal exposure to perfluorooctane sulfonic acid results in
      changes in miRNA expression profiles and synapse associated proteins in
      developing rat brains.
AB  - We previously identified a number of perfluorooctane sulfonic acid (PFOS)
      responsive transcripts in developing rat brains using microarray analysis.
      However, the underlying mechanisms and functional consequences remain unclear. We
      hypothesized that microRNAs (miRNAs), which have emerged as powerful negative
      regulators of mRNA and protein levels, might be responsible for PFOS-induced mRNA
      changes and consequent neural dysfunctions. We used eight miRNA arrays to profile
      the expression of brain miRNAs in neonatal rats on postnatal days (PND) 1 and 7
      with maternal treatment of 0 (Control) and 3.2 mg/kg of PFOS feed from
      gestational day 1 to PND 7, and subsequently examined six potentially altered
      synapse-associated proteins to evaluate presumptive PFOS-responsive functions.
      Twenty-four brain miRNAs on PND 1 and 17 on PND 7 were significantly altered with
      PFOS exposure (P < 0.05), with miR-466b, -672, and -297, which are critical in
      neurodevelopment and synapse transmission, showing a more than 5-fold reduction.
      Levels of three synapse-involved proteins, NGFR, TrkC, and VGLUT2, were
      significantly decreased with no protein up-regulated on PND 1 or 7.
      Perfluorooctane sulfonic acid might affect calcium actions during synapse
      transmission in the nervous system by interfering with SYNJ1, ITPR1, and CALM1
      via their targeting miRNAs. Our results indicated that miRNA had little direct
      regulatory effect on the expression of mRNAs and synapse-associated proteins
      tested in the developing rat brain exposed to PFOS, and it seems that the PFOS
      induced synaptic dysfunctions and changes in transcripts resulted from a
      combinatory action of biological controllers and processes, rather than directed
      by one single factor.

PMID- 22594573
TI  - Toward optimized light utilization in nanowire arrays using scalable nanosphere
      lithography and selected area growth.
AB  - Vertically aligned, catalyst-free semiconducting nanowires hold great potential
      for photovoltaic applications, in which achieving scalable synthesis and
      optimized optical absorption simultaneously is critical. Here, we report
      combining nanosphere lithography (NSL) and selected area metal-organic chemical
      vapor deposition (SA-MOCVD) for the first time for scalable synthesis of
      vertically aligned gallium arsenide nanowire arrays, and surprisingly, we show
      that such nanowire arrays with patterning defects due to NSL can be as good as
      highly ordered nanowire arrays in terms of optical absorption and reflection.
      Wafer-scale patterning for nanowire synthesis was done using a polystyrene
      nanosphere template as a mask. Nanowires grown from substrates patterned by NSL
      show similar structural features to those patterned using electron beam
      lithography (EBL). Reflection of photons from the NSL-patterned nanowire array
      was used as a measure of the effect of defects present in the structure.
      Experimentally, we show that GaAs nanowires as short as 130 nm show reflection of
      <10% over the visible range of the solar spectrum. Our results indicate that a
      highly ordered nanowire structure is not necessary: despite the "defects" present
      in NSL-patterned nanowire arrays, their optical performance is similar to "defect
      free" structures patterned by more costly, time-consuming EBL methods. Our
      scalable approach for synthesis of vertical semiconducting nanowires can have
      application in high-throughput and low-cost optoelectronic devices, including
      solar cells.

PMID- 22594574
TI  - Accuracy of intraocular lens power calculations in eyes with axial length <22.00
      mm.
AB  - BACKGROUND: To assess the accuracy of Haigis, Holladay 1, Hoffer Q and SRK/T
      formulae in eyes with axial length of <22.00 mm. DESIGN: Retrospective
      comparative analysis. PARTICIPANTS: 163 eyes of 97 patients undergoing
      phacoemulsification and intraocular lens (IOL) implantation. METHODS: Ocular
      biometry was performed using IOLMaster laser interferometry. Predicted refractive
      outcomes before and after lens constant adjustment were compared to actual
      refractive outcomes. MAIN OUTCOME MEASURES: Mean prediction (ME) and mean
      absolute errors (MAE) with standard deviations (+/-SD). RESULTS: Mean
      preoperative spherical equivalent was +5.44D +/- 1.97D. Mean axial length was
      21.20 mm +/- 0.60 mm. Using standard IOL constants the MAE for Hoffer Q (0.62D,
      +/-0.52D) and Holladay 1 (0.66D +/- 0.52D) were significantly lower than SRK/T
      (MAE 0.91D +/- 0.64D; P = <0.0005 and P = 0.001 respectively), but not Haigis
      (MAE 0.82D +/- 0.83D, P = 0.071 and 0.22 respectively). MAEs for all formulae
      were significantly reduced by IOL constant adjustment (all P = <0.001). Following
      this there was no statistically significant difference in MAEs between formulae
      (range 0.50-0.57D, P = 0.57). Increasing MAE was significantly associated with
      reducing axial length and increasing IOL power for all formulae. For bilateral
      cases, prediction errors between eyes were significantly correlated across all
      formulae (all P = <0.0001) and explained 32-42% of the variance in prediction
      error between eyes. CONCLUSIONS: Prediction of postoperative refraction in
      patients with short axial lengths is challenging and at the limit of current,
      popular IOL formulae. There is now a clear need for prospective studies to assess
      latest generation IOL formulae such as Holladay 2 or Olsen in small eyes.

PMID- 22594575
TI  - Immunization against A/H1N1 pandemic flu (2009-2010) in pediatric patients at
      risk. What might be the most effective strategy? The experience of an health
      district of Northern Italy.
AB  - BACKGROUND: Vaccination coverage rates against pandemic flu were far below those
      required by Italian Public Health Authorities.The aim of this retrospective study
      was to assess how the management of vaccination against pandemic flu in the
      Health District of Piacenza (Northern Italy) had conditioned the adherence of
      patients at risk to the H1N1flu immunization program. METHODS: From a population
      of 27.018 children aged between 6 months and 16 years, 2361 pediatric patients
      considered at risk according to the guidelines of the Ministry of Health were
      enrolled to receive pandemic flu vaccination.Children enrolled in the
      immunization program were vaccinated with one of the following three options: A)
      by their pediatrician in his office after contacting him directly or by phone B)
      by their pediatrician in his office or in a public Health District office with
      the assistance of a nurse after an appointment had been booked by patient's
      parents using a dedicated free of charge phone number C) by a doctor of the
      public Health District after an appointment had been booked as for option B
      RESULTS: The best outcomes of population vaccination coverage for pandemic flu
      were achieved when patients were vaccinated with option B (44.2%). For options A
      and C rates coverage results were 22.8% (OR 2,69) and 24.9% (OR 2, 39)
      respectively. CONCLUSION: The results of this study may be taken into account by
      the public health Authorities when planning the management of future immunization
      campaigns out of the usual vaccination schedule or in an emergency event.

PMID- 22594576
TI  - Association between a promoter polymorphism (rs2192752, -1028A/C) of interleukin
      1 receptor, type I (IL1R1) and location of papillary thyroid carcinoma in a
      Korean population.
AB  - The interleukin 1 receptor, type I (IL1R1) is important in the pathogenesis of
      cancer. We investigated whether single nucleotide polymorphisms (SNPs) of IL1R1
      contribute to the development of papillary thyroid carcinoma (PTC), in addition
      to the clinicopathological features such as the size, number, location,
      extrathyroidal invasion and metastasis of PTC. Three promoter SNPs (rs949963 
      615G/A, rs2192752 -1028A/C and rs3917225 -1099A/G) in IL1R1 were genotyped using
      direct sequencing in 118 patients with PTC and 347 controls. The odds ratio (OR),
      95% confidence interval (CI) and P value were analysed using SNPStats and
      SNPAnalyzer Pro. For the exact results, Fisher's exact test and Bonferroni
      correction (P(c)) were performed. The three promoter SNPs of IL1R1 were not
      associated with PTC development. For the clinicopathological features of PTC,
      rs2192752 was associated with location (one lobe versus both lobes): dominant
      model, OR = 3.11, 95% CI = 1.39-6.96, P(c) = 0.015; log-additive model, OR =
      2.79, 95% CI = 1.38-5.66, P(c) = 0.0087. The C allele frequency of rs2192752 was
      higher in the both lobes group (28.0%) than the one lobe group (12.3%) (OR =
      2.77, 95% CI = 1.40-5.48, P(c) = 0.009). However, rs949963 and rs3917225 were not
      correlated with clinicopathological features including location of PTC. The IL1R1
      promoter SNP rs2192752 may contribute to the location of PTC, and the C allele of
      rs2192752 may be a risk factor for the development of PTC in both lobes.

PMID- 22594577
TI  - Extracellular DNA oxidation stimulates activation of NRF2 and reduces the
      production of ROS in human mesenchymal stem cells.
AB  - INTRODUCTION: Human blood normally contains circulating cell-free DNA (cirDNA).
      Cell-free DNA (cfDNA) present in cell culture medium is termed extracellular DNA
      (ecDNA). Its concentration, GC content and oxidation level depend on
      physiological state of the organism. cirDNA could probably be one of the
      aggressive factors encountered by therapeutic stem cells. The authors hypothesize
      that oxidized cirDNA could influence their survival rate. They aimed to uncover
      the effects of oxidized ecDNAs, including ecDNA of cultivated primary tumor cells
      and cirDNA from blood plasma of cancer patients on mesenchymal stem cells (MSCs).
      AREAS COVERED: Increased concentrations of cfDNA stimulate a rapid increase in
      reactive oxygen species (ROS) synthesis and up-regulate antioxidant response
      genes (NRF2, KEAP1, SOD1, BRCA1, BCL2) in MSCs. This response is more prominent
      when cfDNA contains higher proportions of 8-oxo-dG. Within an hour, oxidized DNA
      induces a decrease in ROS production while NRF2 mRNA levels continue to augment
      and the NRF2 protein translocates into the nucleus. Additionally, oxidized DNA up
      regulates PPRAG2 with no apparent induction of adipogenesis. This kind of
      response is specific for MSCs. EXPERT OPINION: Oxidized cfDNA up-regulates NRF2
      and PPARG2 and reduces ROS production in MSCs. These effects should be taken into
      account when considering therapeutic applications of stem cells.

PMID- 22594578
TI  - Higher parity and earlier age at first birth are associated with lower risk of
      death from colon cancer.
AB  - This study was undertaken to examine whether there is an association between
      parity and age at first birth and risk of colon cancer. The study cohort
      consisted of 1,292,462 women who had a first and singleton childbirth between
      1978 and 1987. We tracked each woman from the time of their first childbirth to
      December 31, 2009, and their vital status was ascertained by linking records with
      the computerized mortality database. We used the Cox proportional hazards model
      with time-dependent covariates to estimate the hazard ratios (HR) of death from
      colon cancer associated with parity and age at first birth. We limited eligible
      colon cancer deaths to those who were 45 years old or more to exclude possible
      heredity colon cancer cases, which usually occur at an early age. There were 670
      colon cancer deaths during 34,980,246 person-years of follow-up. The colon cancer
      death rate was 1.96 cases per 100,000 person-years. The adjusted HR was 2.76 (95%
      CI = 1.60-4.75) for women who gave birth between 20 and 24 years and 7.35 (95% CI
      = 4.28-12.62) for women who gave birth after 24 years of age when compared with
      women who gave birth at younger than 20 years. A rising risk of colon cancer was
      seen with increasing age at first birth. The adjusted HR were 0.81 (95% CI = 0.65
      1.02) among women with two live births, 0.93 (95% CI = 0.74-1.18) among women
      with three live births and 0.72 (95% CI = 0.51-1.00) for women with four or more
      births when compared with women who had given birth to only one child. The
      present study provides evidence that reproductive factors (parity and early age
      at first birth) may confer a protective effect on the risk of colon cancer.

PMID- 22594579
TI  - The validity of ear prediction guidelines used in facial approximation.
AB  - This study examined eight previously published ear prediction methods by Welcker,
      Gerasimov, Fedosyutkin and Nainys, and Broadbent and Mathews. Computed tomography
      scans of 78 living adults (n(1)) did not support any of these previously
      published recommendations. Free earlobes were found to accompany protruding
      supramastoid crests (Pearson's chi2 < 0.05); and ear length [l] and width [w]
      differed by sex (p < 0.05), correlated with age (r = 0.38[l]; 0.32[w]), and
      correlated with facial height (r = 0.37[l]; 0.30[w]). New regression equations
      (for ear length and width) were generated using these variables in several
      samples and, where possible, cross-validated using independent data (n(1) = 78,
      n(2) = 2190, n(3) = 1328, n(4) = 1010, and n(5) = 47). As a result of these
      analyses, four valid and tested methods for ear prediction were identified, but
      large degrees of error continue to make accurate prediction of the ear, from the
      skull, problematic.

PMID- 22594580
TI  - The effect of laparoscopic surgery in stage II and III right-sided colon cancer:
      a retrospective study.
AB  - BACKGROUND: This retrospective study compared the clinicopathological results
      among three groups divided by time sequence to evaluate the impact of introducing
      laparoscopic surgery on long-term oncological outcomes for right-sided colon
      cancer. METHODS: From April 1986 to December 2006, 200 patients who underwent
      elective surgery with stage II and III right-sided colon cancer were analyzed.
      The period for group I referred back to the time when laparoscopic approach had
      not yet been introduced. The period for group II was designated as the time when
      first laparoscopic approach for right colectomy was carried out until we overcame
      its learning curve. The period for group III was the period after overcoming this
      learning curve. RESULTS: When groups I and II, and groups II and III were
      compared, overall survival (OS) did not differ significantly whereas disease-free
      survival (DFS) in groups I and III were statistically higher than in group II (P
      = 0.042 and P = 0.050). In group III, laparoscopic surgery had a tendency to
      provide better long-term OS ( P = 0.2036) and DFS ( P = 0.2356) than open
      surgery. Also, the incidence of local recurrence in group III (2.6%) was
      significantly lower than that in groups II (7.4%) and I (12.1%) ( P = 0.013).
      CONCLUSIONS: Institutions should standardize their techniques and then provide
      fellowship training for newcomers of laparoscopic colon cancer surgery. This
      technique once mastered will become the gold standard approach to colon surgery
      as it is both safe and feasible considering the oncological and technical
      aspects.

PMID- 22594582
TI  - Population balance modeling of antibodies aggregation kinetics.
AB  - The aggregates morphology and the aggregation kinetics of a model monoclonal
      antibody under acidic conditions have been investigated. Growth occurs via
      irreversible cluster-cluster coagulation forming compact, fractal aggregates with
      fractal dimension of 2.6. We measured the time evolution of the average radius of
      gyration, <R(g)>, and the average hydrodynamic radius, <R(h)>, by in situ light
      scattering, and simulated the aggregation kinetics by a modified Smoluchowski's
      population balance equations. The analysis indicates that aggregation does not
      occur under diffusive control, and allows quantification of effective
      intermolecular interactions, expressed in terms of the Fuchs stability ratio (W).
      In particular, by introducing a dimensionless time weighed on W, the time
      evolutions of <R(h)> measured under various operating conditions (temperature,
      pH, type and concentration of salt) collapse on a single master curve. The
      analysis applies also to data reported in the literature when growth by cluster
      cluster coagulation dominates, showing a certain level of generality in the
      antibodies aggregation behavior. The quantification of the stability ratio gives
      important physical insights into the process, including the Arrhenius dependence
      of the aggregation rate constant and the relationship between monomer-monomer and
      cluster-cluster interactions. Particularly, it is found that the reactivity of
      non-native monomers is larger than that of non-native aggregates, likely due to
      the reduction of the number of available hydrophobic patches during aggregation.

PMID- 22594581
TI  - Kidney function and risk of cardiovascular disease and mortality in kidney
      transplant recipients: the FAVORIT trial.
AB  - In kidney transplant recipients, cardiovascular disease (CVD) is the leading
      cause of death. The relationship of kidney function with CVD outcomes in
      transplant recipients remains uncertain. We performed a post hoc analysis of the
      Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial to
      assess risk factors for CVD and mortality in kidney transplant recipients.
      Following adjustment for demographic, clinical and transplant characteristics,
      and traditional CVD risk factors, proportional hazards models were used to
      explore the association of estimated GFR with incident CVD and all-cause
      mortality. In 4016 participants, mean age was 52 years and 20% had prior CVD.
      Mean eGFR was 49 +/- 18 mL/min/1.73 m(2) . In 3676 participants with complete
      data, there were 527 CVD events over a median of 3.8 years. Following adjustment,
      each 5 mL/min/1.73 m(2) higher eGFR at levels below 45 mL/min/1.73 m(2) was
      associated with a 15% lower risk of both CVD [HR = 0.85 (0.80, 0.90)] and death
      [HR = 0.85 (0.79, 0.90)], while there was no association between eGFR and
      outcomes at levels above 45 mL/min/1.73 m(2) . In conclusion, in stable kidney
      transplant recipients, lower eGFR is independently associated with adverse
      events, suggesting that reduced kidney function itself rather than preexisting
      comorbidity may lead to CVD.

PMID- 22594583
TI  - Perfluorooctane sulfonamide-mediated modulation of hepatocellular lipid
      homeostasis and oxidative stress responses in Atlantic salmon hepatocytes.
AB  - We have investigated the effects of perfluorooctane sulfonamide (PFOSA) on
      cellular functions and lipid homeostasis (including beta-oxidation) in salmon
      primary hepatocytes. Salmon hepatocytes were exposed to PFOSA at 0 (control), 2,
      20, and 50 MUM for 12 and 24 h. Fatty acids (FAs) and lipids were determined by
      GC-MS; FA elongase (FAE), Delta5-desaturase (FAD5), Delta6-desaturase (FAD6),
      peroxisome proliferator-activated receptors (PPARs), acyl coenzyme A (ACOX-1),
      glutathione peroxidase (GPx), catalase (CAT), and glutathione S-transferase (GST)
      mRNA were analyzed using qPCR. GST activity was analyzed by biochemical assays
      using 1-chloro-2,4-dinitrobenzene (CDNB) as substrate. Our data showed that PFOSA
      produced significant changes in FA composition that predominantly involved a
      decrease (at 12 h) and an increase (at 24 h) in FA methyl esters (FAMEs), MUFA,
      total PUFA, and (n-3 and n-6) PUFA. Particularly, an increase of alpha-linolenic
      acid (ALA; 18:3n-3), eicosapentaenoic acid [EPA; 20:5n-3], and arachidonic acid
      [ARA: 20:4n-6] with associated increase in FAE, FAD5, and FAD6 mRNA were observed
      after PFOSA exposure, while cis-13,16-docosadienoic acid (22:2) was significantly
      decreased. PFOSA produced apparent concentration-dependent increase of PPARalpha
      and PPARgamma. CAT, GPx, and GST mRNA show that PFOSA produced concentration- and
      time-specific increase of CAT and GST, but no changes in GST activity were
      observed. In general, these responses indicate that PFOSA evokes deleterious
      effects on cellular lipid homeostasis and transcriptional responses that regulate
      cellular oxidative homeostasis in salmon hepatocytes.

PMID- 22594584
TI  - A novel multiplex PCR-RFLP method for simultaneous detection of the MTHFR 677 C >
      T, eNOS +894 G > T and - eNOS -786 T > C variants among Malaysian Malays.
AB  - BACKGROUND: Hyperhomocysteinemia as a consequence of the MTHFR 677 C > T variant
      is associated with cardiovascular disease and stroke. Another factor that can
      potentially contribute to these disorders is a depleted nitric oxide level, which
      can be due to the presence of eNOS +894 G > T and eNOS -786 T > C variants that
      make an individual more susceptible to endothelial dysfunction. A number of
      genotyping methods have been developed to investigate these variants. However,
      simultaneous detection methods using polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) analysis are still lacking. In this
      study, a novel multiplex PCR-RFLP method for the simultaneous detection of MTHFR
      677 C > T and eNOS +894 G > T and eNOS -786 T > C variants was developed. A total
      of 114 healthy Malay subjects were recruited. The MTHFR 677 C > T and eNOS +894 G
      > T and eNOS -786 T > C variants were genotyped using the novel multiplex PCR
      RFLP and confirmed by DNA sequencing as well as snpBLAST. Allele frequencies of
      MTHFR 677 C > T and eNOS +894 G > T and eNOS -786 T > C were calculated using the
      Hardy Weinberg equation. METHODS: The 114 healthy volunteers were recruited for
      this study, and their DNA was extracted. Primer pair was designed using Primer 3
      Software version 0.4.0 and validated against the BLAST database. The primer
      specificity, functionality and annealing temperature were tested using uniplex
      PCR methods that were later combined into a single multiplex PCR. Restriction
      Fragment Length Polymorphism (RFLP) was performed in three separate tubes
      followed by agarose gel electrophoresis. PCR product residual was purified and
      sent for DNA sequencing. RESULTS: The allele frequencies for MTHFR 677 C > T were
      0.89 (C allele) and 0.11 (T allele); for eNOS +894 G > T, the allele frequencies
      were 0.58 (G allele) and 0.43 (T allele); and for eNOS -786 T > C, the allele
      frequencies were 0.87 (T allele) and 0.13 (C allele). CONCLUSIONS: Our PCR-RFLP
      method is a simple, cost-effective and time-saving method. It can be used to
      successfully genotype subjects for the MTHFR 677 C > T and eNOS +894 G > T and
      eNOS -786 T > C variants simultaneously with 100% concordance from DNA sequencing
      data. This method can be routinely used for rapid investigation of the MTHFR 677
      C > T and eNOS +894 G > T and eNOS -786 T > C variants.

PMID- 22594585
TI  - Four essays.

PMID- 22594586
TI  - Aromatic transition states in nonpericyclic reactions: anionic 5-endo
      cyclizations are aborted sigmatropic shifts.
AB  - The transition states (TSs) of 5-endo-dig and 5-endo-trig anionic ring closures
      are the first unambiguous examples of nonpericyclic reactions with TSs stabilized
      by aromaticity. Their five-center, six-electron in-plane aromaticity is revealed
      by the diatropic dissected nucleus-independent chemical shifts, -24.1 and -13.7
      ppm, respectively, resulting from the delocalization of the lone pair at the
      nucleophilic center, a sigma CC bond, and an in-plane alkyne (or alkene) pi bond.
      Other seemingly analogous exo and endo cyclization TSs do not have these
      features. A symmetry-enhanced combination of through-space and through-bond
      interactions explains the anomalous geometric, energetic, and electronic features
      of the 5-endo ring closure transition state. Anionic 5-endo cyclizations can be
      considered to be "aborted" [2,3]-sigmatropic shifts. The connection between
      anionic cyclizations and sigmatropic shifts offers new possibilities for the
      design and electronic control of anionic isomerizations.

PMID- 22594587
TI  - WebDASC: a web-based dietary assessment software for 8-11-year-old Danish
      children.
AB  - BACKGROUND:   The present study describes the development and formative
      evaluation of the Web-based Dietary Assessment Software for Children (WebDASC).
      WebDASC is part of the OPUS project ('Optimal well-being, development and health
      for Danish children through a healthy New Nordic Diet') and was intended to
      measure dietary change resulting from a school-based intervention. METHODS:  
      WebDASC was developed as a self-administered tool that could be used by 8-11-year
      old children with or without parent's aid. The development of WebDASC followed a
      prototyping approach: focus groups, informal interviews, literature review, and
      usability tests preceded its release. Special consideration was given to age
      appropriate design issues. RESULTS:   In WebDASC an animated armadillo guides
      respondents through six daily eating occasions and helps them report foods and
      beverages previously consumed. A database of 1300 food items is available either
      through category browse or free text search, aided by a spell check application.
      A type-in format is available for foods not otherwise found through category
      browse or text search. Amount consumed is estimated by selecting the closest
      portion size among four different digital images. WebDASC includes internal
      checks for frequently forgotten foods, and the following features to create
      motivation: a food-meter displaying cumulative weight of foods reported, a most
      popular food ranking, and a computer game with a high score list. CONCLUSIONS:  
      WebDASC was developed as an intuitive, cost-effective, and engaging method to
      collect detailed dietary data from 8- to 11-year-old children. Preliminary
      testing demonstrated that it was well accepted among children.

PMID- 22594588
TI  - Functional electrical stimulation by nanogenerator with 58 V output voltage.
AB  - We demonstrate a new type of integrated nanogenerator based on arrays of
      vertically aligned piezoelectric ZnO nanowires. The peak open-circuit voltage and
      short-circuit current reach a record high level of 58 V and 134 MUA,
      respectively, with a maximum power density of 0.78 W/cm(3). The electric output
      was directly applied to a sciatic nerve of a frog, inducing innervation of the
      nerve. Vibrant contraction of the frog's gastrocnemius muscle is observed as a
      result of the instantaneous electric input from the nanogenerator.

PMID- 22594589
TI  - Science on whales, submarines, and conservation meets the news.

PMID- 22594590
TI  - The politics of opting out.

PMID- 22594592
TI  - Conservation focus: Costs of adapting conservation to climate change.
      Introduction.

PMID- 22594593
TI  - Human perspectives and conservation of grizzly bears in Banff National Park,
      Canada.
AB  - Some conservation initiatives provoke intense conflict among stakeholders. The
      need for action, the nature of the conservation measures, and the effects of
      these measures on human interests may be disputed. Tools are needed to depolarize
      such situations, foster understanding of the perspectives of people involved, and
      find common ground. We used Q methodology to explore stakeholders' perspectives
      on conservation and management of grizzly bears (Ursus arctos horribilis) in
      Banff National Park and the Bow River watershed of Alberta, Canada. Twenty-nine
      stakeholders participated in the study, including local residents, scientists,
      agency employees, and representatives of nongovernmental conservation
      organizations and other interest groups. Participants rank ordered a set of
      statements to express their opinions on the problems of grizzly bear management
      (I-IV) and a second set of statements on possible solutions to the problems (A
      C). Factor analysis revealed that participants held 4 distinct views of the
      problems: individuals associated with factor I emphasized deficiencies in goals
      and plans; those associated with factor II believed that problems had been
      exaggerated; those associated with factor III blamed institutional flaws such as
      disjointed management and inadequate resources; and individuals associated with
      factor IV blamed politicized decision making. There were 3 distinct views about
      the best solutions to the problems: individuals associated with factor A called
      for increased conservation efforts; those associated with factor B wanted reforms
      in decision-making processes; and individuals associated with factor C supported
      active landscape management. We connected people's definitions of the problem
      with their preferred solutions to form 5 overall problem narratives espoused by
      groups in the study: the problem is deficient goals and plans, the solution is to
      prioritize conservation efforts (planning-oriented conservation advocates); the
      problem is flawed institutions, the solution is to prioritize conservation
      efforts (institutionally-oriented conservation advocates); the problems have been
      exaggerated, but there is a need to improve decision-making processes (optimistic
      decision-process reformers); the problems have been exaggerated, but managers
      should more actively manage the landscape (optimistic landscape managers); and
      the problem is politicized decision making, solutions vary (democratizers).
      Although these 5 groups differed on many issues, they agreed that the population
      of grizzly bears is vulnerable to extirpation, human use of the area should be
      designed around ecological constraints, and more inclusive decision-making
      processes are needed. We used our results to inform a series of workshops in
      which stakeholders developed and agreed on new management strategies that were
      implemented by Parks Canada. Our research demonstrates the usefulness of Q method
      to illuminate people's perspectives and identify common ground in settings where
      conservation is contested.

PMID- 22594594
TI  - Efficient species-level monitoring at the landscape scale.
AB  - Monitoring the population trends of multiple animal species at a landscape scale
      is prohibitively expensive. However, advances in survey design, statistical
      methods, and the ability to estimate species presence on the basis of detection
      nondetection data have greatly increased the feasibility of species-level
      monitoring. For example, recent advances in monitoring make use of detection
      nondetection data that are relatively inexpensive to acquire, historical survey
      data, and new techniques in genetic evaluation. The ability to use indirect
      measures of presence for some species greatly increases monitoring efficiency and
      reduces survey costs. After adjusting for false absences, the proportion of
      sample units in a landscape where a species is detected (occupancy) is a logical
      state variable to monitor. Occupancy monitoring can be based on real-time
      observation of a species at a survey site or on evidence that the species was at
      the survey location sometime in the recent past. Temporal and spatial patterns in
      occupancy data are related to changes in animal abundance and provide insights
      into the probability of a species' persistence. However, even with the
      efficiencies gained when occupancy is the monitored state variable, the task of
      species-level monitoring remains daunting due to the large number of species. We
      propose that a small number of species be monitored on the basis of specific
      management objectives, their functional role in an ecosystem, their sensitivity
      to environmental changes likely to occur in the area, or their conservation
      importance.

PMID- 22594595
TI  - Experimental evidence for the effects of chronic anthropogenic noise on abundance
      of Greater Sage-Grouse at leks.
AB  - Increasing evidence suggests that chronic noise from human activities negatively
      affects wild animals, but most studies have failed to separate the effects of
      chronic noise from confounding factors, such as habitat fragmentation. We played
      back recorded continuous and intermittent anthropogenic sounds associated with
      natural gas drilling and roads at leks of Greater Sage-Grouse (Centrocercus
      urophasianus). For 3 breeding seasons, we monitored sage grouse abundance at leks
      with and without noise. Peak male attendance (i.e., abundance) at leks
      experimentally treated with noise from natural gas drilling and roads decreased
      29% and 73%, respectively, relative to paired controls. Decreases in abundance at
      leks treated with noise occurred in the first year of the study and continued
      throughout the experiment. Noise playback did not have a cumulative effect over
      time on peak male attendance. There was limited evidence for an effect of noise
      playback on peak female attendance at leks or male attendance the year after the
      experiment ended. Our results suggest that sage-grouse avoid leks with
      anthropogenic noise and that intermittent noise has a greater effect on
      attendance than continuous noise. Our results highlight the threat of
      anthropogenic noise to population viability for this and other sensitive species.

PMID- 22594596
TI  - Effects of flow regimes altered by dams on survival, population declines, and
      range-wide losses of California river-breeding frogs.
AB  - Widespread alteration of natural hydrologic patterns by large dams combined with
      peak demands for power and water delivery during summer months have resulted in
      frequent aseasonal flow pulses in rivers of western North America. Native species
      in these ecosystems have evolved with predictable annual flood-drought cycles;
      thus, their likelihood of persistence may decrease in response to disruption of
      the seasonal synchrony between stable low-flow conditions and reproduction. We
      evaluated whether altered flow regimes affected 2 native frogs in California and
      Oregon (U.S.A.) at 4 spatial and temporal extents. We examined changes in species
      distribution over approximately 50 years, current population density in 11
      regulated and 16 unregulated rivers, temporal trends in abundance among
      populations occupying rivers with different hydrologic histories, and within-year
      patterns of survival relative to seasonal hydrology. The foothill yellow-legged
      frog (Rana boylii), which breeds only in flowing water, is more likely to be
      absent downstream of large dams than in free-flowing rivers, and breeding
      populations are on average 5 times smaller in regulated rivers than in
      unregulated rivers. Time series data (range = 8 - 19 years) from 5 populations of
      yellow-legged frogs and 2 populations of California red-legged frogs (R.
      draytonii) across a gradient of natural to highly artificial timing and magnitude
      of flooding indicate that variability of flows in spring and summer is strongly
      correlated with high mortality of early life stages and subsequent decreases in
      densities of adult females. Flow management that better mimics natural flow
      timing is likely to promote persistence of these species and others with similar
      phenology.

PMID- 22594597
TI  - Protected areas as frontiers for human migration.
AB  - Causes of human population growth near protected areas have been much debated. We
      conducted 821 interviews in 16 villages around Budongo Forest Reserve, Masindi
      district, Uganda, to explore the causes of human migration to protected areas and
      to identify differences in forest use between migrant and nonmigrant communities.
      We asked subjects for information about birthplace, migration, household assets,
      household activities, and forest use. Interview subjects were categorized as
      nonmigrants (born in one of the interview villages), socioeconomic migrants
      (chose to emigrate for economic or social reasons) from within Masindi district
      (i.e., local migrants) and from outside the Masindi district (i.e., regional
      migrants), or forced migrants (i.e., refugees or internally displaced individuals
      who emigrated as a result of conflict, human rights abuses, or natural disaster).
      Only 198 respondents were born in interview villages, indicating high rates of
      migration between 1998 and 2008. Migrants were drawn to Budongo Forest because
      they thought land was available (268 individuals) or had family in the area (161
      individuals). A greater number of regional migrants settled in villages near Lake
      Albert than did forced and local migrants. Migration category was also associated
      with differences in sources of livelihood. Of forced migrants 40.5% earned wages
      through labor, whereas 25.5% of local and 14.5% of regional migrants engaged in
      wage labor. Migrant groups appeared to have different effects on the environment.
      Of respondents that hunted, 72.7% were regional migrants. Principal component
      analyses indicated households of regional migrants were more likely to be
      associated with deforestation. Our results revealed gaps in current models of
      human population growth around protected areas. By highlighting the importance of
      social networks and livelihood choices, our results contribute to a more nuanced
      understanding of causes of migration and of the environmental effects of
      different migrant groups.

PMID- 22594598
TI  - Priority actions for sustainable forest management in the International Year of
      Forests.

PMID- 22594602
TI  - Comment on "Surface urban heat island across 419 global big cities".

PMID- 22594601
TI  - Method: a single nucleotide polymorphism genotyping method for Wheat streak
      mosaic virus.
AB  - BACKGROUND: The September 11, 2001 attacks on the World Trade Center and the
      Pentagon increased the concern about the potential for terrorist attacks on many
      vulnerable sectors of the US, including agriculture. The concentrated nature of
      crops, easily obtainable biological agents, and highly detrimental impacts make
      agroterrorism a potential threat. Although procedures for an effective criminal
      investigation and attribution following such an attack are available, important
      enhancements are still needed, one of which is the capability for fine
      discrimination among pathogen strains. The purpose of this study was to develop a
      molecular typing assay for use in a forensic investigation, using Wheat streak
      mosaic virus (WSMV) as a model plant virus. METHOD: This genotyping technique
      utilizes single base primer extension to generate a genetic fingerprint. Fifteen
      single nucleotide polymorphisms (SNPs) within the coat protein and helper
      component-protease genes were selected as the genetic markers for this assay.
      Assay optimization and sensitivity testing was conducted using synthetic targets.
      WSMV strains and field isolates were collected from regions around the world and
      used to evaluate the assay for discrimination. The assay specificity was tested
      against a panel of near-neighbors consisting of genetic and environmental near
      neighbors. RESULT: Each WSMV strain or field isolate tested produced a unique SNP
      fingerprint, with the exception of three isolates collected within the same
      geographic location that produced indistinguishable fingerprints. The results
      were consistent among replicates, demonstrating the reproducibility of the assay.
      No SNP fingerprints were generated from organisms included in the near-neighbor
      panel, suggesting the assay is specific for WSMV. Using synthetic targets, a
      complete profile could be generated from as low as 7.15 fmoles of cDNA.
      CONCLUSION: The molecular typing method presented is one tool that could be
      incorporated into the forensic science tool box after a thorough validation
      study. This method incorporates molecular biology techniques that are already
      well established in research and diagnostic laboratories, allowing for an easy
      introduction of this method into existing laboratories. KEYWORDS: single
      nucleotide polymorphisms, genotyping, plant pathology, viruses, microbial
      forensics, Single base primer extension, SNaPshot Multiplex Kit.

PMID- 22594603
TI  - Commentary on Wagener et al. (2012): E-cigarettes: a vulnerable promise.

PMID- 22594604
TI  - Psychotherapy as an epigenetic 'drug': psychiatric therapeutics target symptoms
      linked to malfunctioning brain circuits with psychotherapy as well as with drugs.
AB  - WHAT IS KNOWN AND OBJECTIVE: Psychotherapy has traditionally competed with
      psychopharmacology. As drugs have become the more dominant treatment in
      psychiatry and primary care, this approach is increasingly criticized as limited
      in scope, lacking in robust outcomes and too heavily influenced by the
      pharmaceutical industry. Our objective is to show that recent advances in
      neurobiology are clarifying that learning and environmental experiences, such as
      psychotherapy, change brain circuits as do drugs. The leading notion of how
      therapeutic effects occur in psychiatric disorders is that they happen when
      symptoms are reduced by improving the efficiency of information processing in
      hypothetically malfunctioning brain circuits. COMMENT: With this formulation of
      psychiatric symptoms and their relief, it is not surprising that both
      psychotherapy and psychopharmacology can be clinically effective for treating
      psychiatric disorders, or indeed that combining them can be therapeutically
      synergistic. Psychotherapy, including a new spinoff of cognitive behavioural
      therapy called trial-based therapy, like many other forms of learning, can
      hypothetically induce epigenetic changes in brain circuits that can enhance the
      efficiency of information processing in malfunctioning neurons to improve
      symptoms in psychiatric disorders, just like drugs. WHAT IS NEW AND CONCLUSION:
      Psychotherapies can be conceptualized as epigenetic 'drugs', or at least as
      therapeutic agents that act epigenetically in a manner similar or complementary
      to drugs. These findings are leading to a paradigm shift in psychiatry such that
      psychotherapy is experiencing a come-back as various standardized, brief, goal
      directed psychotherapies are being integrated with drug treatment of psychiatric
      disorders by psychopharmacologists who have traditionally relied on a drugs-only
      approach.

PMID- 22594605
TI  - A new pyrimidinedione derivative from the gorgonian coral Verrucella umbraculum.
AB  - A new pyrimidinedione derivative, 9-acetyl-1,3,7-trimethyl-pyrimidinedione (1),
      was isolated from the gorgonian coral Verrucella umbraculum, together with two
      known compounds, caffeine (2) and 1,3-dimethylpyrimidine-2,4(1H,3H)-dione (3).
      The structure of 1 was elucidated by the aid of 1D, 2D NMR and MS experiments.
      The structures of the known compounds were identified by comparison of their
      spectroscopic data with those reported in the literature.

PMID- 22594606
TI  - An impedance-manometry based method for non-radiological detection of pharyngeal
      postswallow residue.
AB  - BACKGROUND: Postswallow residue is indicative of impaired pharyngeal bolus
      clearance. The integrated nadir impedance to impedance ratio (iZn/Z) is a novel
      functional variable that can be derived using automated impedance manometry
      (AIM). In this study, the postswallow pharyngeal iZn/Z was evaluated as a
      potential correlated postswallow residue and therefore predictor of ineffective
      swallowing. METHODS: Optimal iZn/Z criteria were determine using a database of 50
      randomly selected bolus swallows recorded with impedance, manometry, and
      videofluoroscopy. The iZn/Z was derived for a region of interest (ROI), spanning
      the mid-point of the pharyngeal stripping wave to the upper esophageal sphincter
      proximal margin, and from 0.25 to 1.25 s after the peak of the pharyngeal
      stripping wave. Videofluorscopy was scored by four experts using a six-point
      bolus residue scale (BRS) score. Optimized criteria for iZn/Z were then applied
      to a much larger database of 225 swallows scored for residue by one expert
      observer. KEY RESULTS: Among individual database, swallows iZn/Z was
      significantly correlated with average expert BRS score (r = 0.748, P < 0.0001).
      An iZn/Z of >= 500 was optimally predictive of swallows with residue defined by a
      BRS score of 4 or more. Within the larger cohort, iZn/Z was higher in dysphagia
      patient swallows compared with controls [2 (1, 4) vs 1 (1, 3), P < 0.005] and
      swallows with an iZn/Z >= 500 had higher bolus residue scores [4 (1, 6) vs 2 (1,
      4), P < 0.001]. CONCLUSIONS & INFERENCES: The AIM derived iZn/Z is an easily
      determined objective non-radiological marker of clinically relevant postswallow
      residue and therefore has potential diagnostic relevance as a predictor of
      ineffective swallowing.

PMID- 22594607
TI  - Wireless technologies for robotic endoscope in gastrointestinal tract.
AB  - This paper introduces wireless technologies for use with robotic endoscopes in
      the gastrointestinal tract. The technologies include wireless power transmission
      (WPT), wireless remote control (WRC), and wireless image transmission (WIT). WPT,
      based on the electromagnetic coupling principle, powers active locomotion
      actuators and other peripherals in large air gaps. WRC, based on real-time
      bidirectional communication, has a multikernel frame in vivo to realize real-time
      multitasking. WIT provides a continuous dynamic image with a revolution of 320 *
      240 pixel at 30 fps for in vitro diagnosis. To test these wireless technologies,
      three robotic endoscope prototypes were fabricated and equipped with the
      customized modules. The experimental results show that the wireless technologies
      have value for clinical applications.

PMID- 22594608
TI  - Extracellular GC-rich DNA activates TLR9- and NF-kB-dependent signaling pathways
      in human adipose-derived mesenchymal stem cells (haMSCs).
AB  - INTRODUCTION: The content of GC-rich ribosomal repeats (rDNA) in cell-free DNA
      (cfDNA) of patients with various diseases is several times higher as compared
      with genomic DNA (gDNA) and cfDNA of healthy donors. rDNA may act as Toll-like
      receptor 9 (TLR9) ligands and affect human adipose-derived mesenchymal stem cells
      (haMSCs). Here we explore effects of human cfDNAs and model rDNA fragments on
      cultured haMSCs. AREAS COVERED: Both cfDNAs and cloned rDNA stimulate expression
      of TLR9 (qRT-PCR). Treatment with cloned rDNA leads to an increase in the number
      of TLR9(+) cells (FACS), expression levels for both TLR9 and Myd88, the
      translocation of nuclear factor-kappa B to the nuclei and up-regulation of
      TNFalpha and IL-10 cytokines (ELISA). As shown by an analysis of gammaH2AX-foci
      and MTT test, the preconditioning of haMSCs with cloned rDNA fragment increases
      the resistance of these cells to irradiation at 2Gy, while the treatments with
      control gDNA did not stimulate either TLR9- or NF-kB-dependent signaling
      pathways. EXPERT OPINION: GC-rich sequences present in cfDNA stimulate endogenous
      stems cells when body is exposed to adverse conditions. GC-rich fragments of
      human DNA may be used for preconditioning of therapeutic MSCs aiming at an
      increase in their survival in the ailing body.

PMID- 22594609
TI  - Structure-activity relationship study of selective excitatory amino acid
      transporter subtype 1 (EAAT1) inhibitor 2-amino-4-(4-methoxyphenyl)-7-(naphthalen
      1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (UCPH-101) and absolute
      configurational assignment using infrared and vibrational circular dichroism
      spectroscopy in combination with ab initio Hartree-Fock calculations.
AB  - The excitatory amino acid transporters (EAATs) play essential roles in regulating
      the synaptic concentration of the neurotransmitter glutamate in the mammalian
      central nervous system. To date, five subtypes have been identified, named EAAT1
      5 in humans, and GLAST, GLT-1, EAAC1, EAAT4, and EAAT5 in rodents, respectively.
      In this paper, we present the design, synthesis, and pharmacological evaluation
      of seven 7-N-substituted analogues of UCPH-101/102. Analogue 9 inhibited EAAT1 in
      the micromolar range (IC(50) value 20 MUM), whereas analogues 8 and 10 were
      inactive (IC(50) values >100 MUM). The diastereomeric pairs 11a/11b and 12a/12b
      were separated by HPLC and the absolute configuration assigned by VCD technique
      in combination with ab initio Hartree-Fock calculations. Analogues 11a (RS
      isomer) and 12b (RR-isomer) inhibited EAAT1 (IC(50) values 5.5 and 3.8 MUM,
      respectively), whereas analogues 11b (SS-isomer) and 12a (SR-isomer) failed to
      inhibit EAAT1 uptake (IC(50) values >300 MUM).

PMID- 22594610
TI  - Clinical use of Dieletrophoresis separation for live Adipose derived stem cells.
AB  - BACKGROUND: Microelectrode dieletrophoresis capture of live cells has been
      explored in animal and cellular models ex-vivo. Currently, there is no clinical
      data available regarding the safety and efficacy of dielectrophoresis (DEP)
      buffers and microcurrent manipulation in humans, despite copious pre-clinical
      studies suggesting its safety. The purpose of this study was to determine if DEP
      isolation of SVF using minimal manipulation methods is safe and efficacious for
      use in humans using the hand lipotransfer model. METHODS: Autologous stromal
      vascular fraction cells (SVF) were obtained from lipoaspirate by collagenase
      digestion and centrifugation. The final mixture of live and dead cells was
      further processed using a custom DEP microelectrode array and microcurrent
      generator to isolate only live nucleated cells. Lipotransfer was completed using
      fat graft enhanced with either standard processed SVF (control) versus DEP
      filtered SVF (experimental). Spectral photography, ultrasound and biometric
      measurements were obtained at post operatively days 1, 4, 7, 14, 30, 60 and 90.
      RESULTS: The DEP filter was capable of increasing SVF viability counts from 74.3
      +/- 2.0% to 94.7 +/- 2.1%. Surrogate markers of inflammation (temperature, soft
      tissue swelling, pain and diminished range of motion) were more profound on the
      control hand. Clinical improvement in hand appearance was appreciated in both
      hands, though the control hand exclusively sustained late phase erosive skin
      breaks on post operative day 7. No skin breaks were appreciated on the DEP-SVF
      treated hand. Early fat engraftment failure was noted on the control hand thenar
      web space at 3 months post surgery. DISCUSSION: No immediate hypersensitivity or
      adverse reaction was appreciated with the DEP-SVF treated hand. In fact, the
      control hand experienced skin disruption and mild superficial cellulitis, whereas
      the experimental hand did not experience this complication, suggesting a possible
      "protective" effect with DEP filtered SVF. Late ultrasound survey revealed larger
      and more frequent formation of oil cysts in the control hand, also suggesting
      greater risk of engraftment failure with standard lipotransfer. CONCLUSION:
      Clinical DEP appears safe and efficacious for human use. The DEP microelectrode
      array was found to be versatile and robust in efficiently isolating live SVF
      cells from dead cells and cellular debris in a time sensitive clinical setting.

PMID- 22594611
TI  - Intravenous immunoglobulin as a potential therapy for refractory urticaria - a
      review.
AB  - Urticaria can be a chronic and debilitating affliction and is a relatively common
      disorder affecting between 10- 20% of the population. Common causes include
      reactions to medication, food allergen, physical stimuli and venoms. Urticaria
      can be acute or chronic. Chronic urticaria lasts for more than 6 weeks and is
      commonly difficult to treat. The use of immunosuppressive agents for this
      disorder when antihistamines fail can result in significant morbidity. Recent
      advances in the pathogenesis, etiology, diagnosis and management of chronic
      urticaria have led to new paradigms in treatment of this disorder. Cyclosporine
      is often the most effective but has some unique adverse effects that may prevent
      it from being used in some patients. The use of intravenous immunoglobulin (IVIG)
      has proven effective in a variety of reports and we will review the mechanisms
      likely involved in the successful control of urticarial symptoms by
      immunomodulating therapy using IVIG. In this review, we will discuss mechanisms
      and pathogenesis of urticaria and the specific role of intravenous immunoglobulin
      (IVIG) in this disorder, especially in refractory or steroid-dependent cases.

PMID- 22594612
TI  - Dorsal vaginal graft urethroplasty for female urethral stricture disease.
AB  - Study Type--Therapy (case series) Level of Evidence 4. What's known on the
      subject? and What does the study add? Female urethral stricture disease has been
      described for almost 200 years. The symptoms of female stricture disease may
      range from clinically insignificant to severe and debilitating with the exact
      aetiology being unclear. No strict criteria for diagnosis have been established
      with the diagnosis often relying on a combination of presenting symptoms and
      objective findings. Initial therapy for female urethral stricture disease has
      often rested on urethral dilatations and self-intermittent catheterisation with
      surgery reserved for patients that failed conservative measures. Female
      urethroplasty currently is a topic of increasing attention with multiple surgical
      approaches described including use of both grafts (vaginal wall, buccal mucosal
      membrane, lingual mucosa, and labia minus) and flaps (vaginal vestibule, anterior
      vagina, and lateral vagina). We describe our approach to female urethroplasty
      using a suprameatal (dorsal) approach (described by Tsivian and Sidi) with an
      autologous vaginal epithelium inlay graft. The technique and modern approaches to
      female urethroplasty are contrasted and discussed. The success of the approach
      including continence rates and lack of need for long-term self-intermittent
      catheterisation is noted. OBJECTIVE: * To review the technique and outcomes of
      using a dorsal vaginal graft to perform urethroplasty for the treatment of
      urethral strictures in women. PATIENTS AND METHODS: * This is a retrospective
      chart review of 11 women who were treated with a dorsal vaginal graft
      urethroplasty by one surgeon. * All women underwent preoperative evaluation that
      included history, physical examination, fluoro-urodynamics and urethral
      calibration. * After surgery interviews, physical examinations, and urinary flow
      and postvoid residual urine volumes (PVRs) were obtained. RESULTS: * In all, 11
      women who had undergone dorsal vaginal graft urethroplasty were identified for
      review. The mean (range) age was 60.6 (39-75) years. The mean (range) follow-up
      was 22.7 (6-46) months. * There were no cases of new onset stress urinary
      incontinence. The mean PVRs before and after surgery were 187.1 mL and 75.8 mL,
      respectively (P = 0.003). The mean urinary flows before and after surgery were
      7.3 mL/s and 21.8 mL/s, respectively (P = 0.001). * No patient has required
      repeat surgery. * Self-reporting satisfaction scores using the Patient Global
      Impression of Improvement showed that four patients scored 1 (very much better),
      three scored 2 (much better), two patients scored 3 (a little better), and one
      scored 4 (no change). Only one patient scored a 5 (worse). CONCLUSION: * Dorsal
      graft urethroplasty with vaginal mucosa may be considered as a first-line option
      for definitive management of female urethral stricture disease. No consensus
      exists for the surgical treatment of female urethral stricture disease.

PMID- 22594614
TI  - Phytopathology in a developing country.

PMID- 22594613
TI  - Iris involvement by lymphoma: a review of 13 cases.
AB  - BACKGROUND: To describe the clinical and histopathological features of lymphomas
      involving the iris. DESIGN: Retrospective, descriptive study. PARTICIPANTS:
      Fourteen eyes of 13 patients. METHODS: Review of medical records. MAIN OUTCOME
      MEASURES: Clinical and histopathological findings. RESULTS: Median patient age
      was 58 years (range, 25-76 years). Seven patients had known systemic lymphoma of
      which five were of large B-cell type. Symptoms included blurred vision (8/14),
      eye redness (3/14) and eye pain (2/14). Four eyes had secondary elevated
      intraocular pressure. Anterior segment findings included anterior chamber cells
      (14/14 eyes), keratic precipitates (11/14 eyes), congestion of
      conjunctival/episcleral blood vessels (9/14), hyphaema (7/14),
      conjunctival/anterior epibulbar lymphoma (6/14), tumour-induced pseudohypopyon
      (4/14) and corneal oedema (3/14). Of 12 eyes with adequate view of iris details,
      clinically detectable iris thickening or visible mass was noted in all (12/12).
      There was concomitant involvement of ciliary body (8/14), choroid (5/14) and
      orbit (2/14). All patients had biopsy of conjunctiva, episclera, iris or ciliary
      body, confirming the diagnosis of lymphoma. Histopathological or cytopathological
      evaluation of iris or ciliary body showed high-grade lymphoma in 9/11 eyes in
      which it was performed. Five patients did not have long-term follow up and, of
      the other eight patients, three died from complications of systemic lymphoma
      during follow up ranging from 1 to 44 months. CONCLUSION: Lymphomatous
      involvement of the iris should be considered in the differential diagnosis of
      corticosteroid-resistant uveitis in middle-aged and elderly patients. Iris
      lymphoma tends to be high grade and usually develops in patients with known
      aggressive systemic lymphoma.

PMID- 22594615
TI  - Molecular simulation of the thermophysical properties of N-functionalized
      alkylimidazoles.
AB  - Molecular simulations are used to probe the thermophysical properties of a series
      of N-functionalized alkylimidazoles, ranging from N-methylimidazole to N
      heptylimidazole. These compounds have been previously synthesized, and their
      solvation properties have been shown to be potentially useful for CO(2) capture
      from industrial sources. In this work, we use first-principles calculations to
      fit electrostatic charges to the molecular models, which are then used to perform
      a series of molecular dynamics simulations. Over a range of different
      temperatures, we benchmark the simulated densities and heat capacities against
      experimental measurements. Also, we predict the Henry's constants for CO(2)
      absorption and probe the solvents' structures using molecular simulation
      techniques, such as fractional free volume analysis and void distributions. We
      find that our simulations are able to closely reproduce the experimental
      benchmarks and add additional insight into the molecular structure of these
      fluids, with respect to their observed solvent properties.

PMID- 22594616
TI  - Longitudinal study of volatile fatty acids in the gingival crevicular fluid of
      patients with periodontitis before and after nonsurgical therapy.
AB  - BACKGROUND AND OBJECTIVE:   Short-chain fatty acids (SCFAs) are important
      metabolic products of subgingival organisms and their concentrations are
      associated with the status of inflammation. The purpose of this study was to
      observe and analyze the change in concentration of SCFAs in the gingival
      crevicular fluid of patients with chronic periodontitis before and after
      periodontal treatment. MATERIAL AND METHODS:   Gingival crevicular fluid samples
      were taken from 21 patients with chronic periodontitis before periodontal
      treatment and 2 wk, and 2, 4 and 6 mo after treatment. The concentrations of six
      different SCFAs in the gingival crevicular fluid were measured using high
      performance capillary electrophoresis. The presence of porphyromonas gingivalis
      in the same pretreatment gingival crevicular fluid samples used to measure SCFAs
      was analyzed using PCR amplification. RESULTS: Two weeks after periodontal
      treatment, the concentrations of lactic acid, propionic acid, butyric acid and
      isovaleric acid in the gingival crevicular fluid of patients with chronic
      periodontitis had decreased to the levels found in the healthy control group.
      However, the concentration of formic acid had increased. Statistically
      significant differences were found in the levels of these SCFAs before and after
      treatment. In the longitudinal observation, the concentrations of butyric acid
      and isovaleric acid in the gingival crevicular fluid had increased to a high
      level 2 mo after treatment. At the last two study time-points (4 and 6 mo after
      treatment), butyric acid and isovaleric acid were still present at a high level
      and showed a tendency to continue to increase. In contrast, the concentration of
      formic acid in gingival crevicular fluid showed a gradual decrease over the study
      period. CONCLUSIONS: The concentration of formic acid in the gingival crevicular
      fluid has an inverse relationship with the severity of periodontitis, whereas the
      increased concentrations of butyric and isovelaric acids during the long-term
      observation period after therapy may indicate the status of recolonization of
      periodontal pathogens and reflect the subgingival ecology. These two fatty acids
      could be used as indicators for the development and progression of periodontitis.

PMID- 22594617
TI  - Computational identification and experimental validation of microRNAs binding to
      the Alzheimer-related gene ADAM10.
AB  - BACKGROUND: MicroRNAs (miRNAs) are post-transcriptional regulators involved in
      numerous biological processes including the pathogenesis of Alzheimer's disease
      (AD). A key gene of AD, ADAM10, controls the proteolytic processing of APP and
      the formation of the amyloid plaques and is known to be regulated by miRNA in
      hepatic cancer cell lines. To predict miRNAs regulating ADAM10 expression
      concerning AD, we developed a computational approach. METHODS: MiRNA binding
      sites in the human ADAM10 3' untranslated region were predicted using the RNA22,
      RNAhybrid and miRanda programs and ranked by specific selection criteria with
      respect to AD such as differential regulation in AD patients and tissue-specific
      expression. Furthermore, target genes of miR-103, miR-107 and miR-1306 were
      derived from six publicly available miRNA target site prediction databases. Only
      target genes predicted in at least four out of six databases in the case of miR
      103 and miR-107 were compared to genes listed in the AlzGene database including
      genes possibly involved in AD. In addition, the target genes were used for Gene
      Ontology analysis and literature mining. Finally, we used a luciferase assay to
      verify the potential effect of these three miRNAs on ADAM10 3'UTR in SH-SY5Y
      cells. RESULTS: Eleven miRNAs were selected, which have evolutionary conserved
      binding sites. Three of them (miR-103, miR-107, miR-1306) were further analysed
      as they are linked to AD and most strictly conserved between different species.
      Predicted target genes of miR-103 (p-value = 0.0065) and miR-107 (p-value =
      0.0009) showed significant overlap with the AlzGene database except for miR-1306.
      Interactions between miR-103 and miR-107 to genes were revealed playing a role in
      processes leading to AD. ADAM10 expression in the reporter assay was reduced by
      miR-1306 (28%), miR-103 (45%) and miR-107 (52%). CONCLUSIONS: Our approach shows
      the requirement of incorporating specific, disease-associated selection criteria
      into the prediction process to reduce the amount of false positive predictions.
      In summary, our method identified three miRNAs strongly suggested to be involved
      in AD, which possibly regulate ADAM10 expression and hence offer possibilities
      for the development of therapeutic treatments of AD.

PMID- 22594618
TI  - How to engage children in self-administered dietary assessment programmes.
AB  - Effectively assessing children's dietary intake is essential for understanding
      the complex relationships among dietary behaviours and obesity. Dietary
      assessment accuracy decreases when children are unable or unmotivated to complete
      accurate self-reports. Technology-based assessment instruments for children's
      self-report of diet can be enhanced in light of developments in media psychology
      and communication science. To motivate children to complete a dietary assessment,
      researchers could use animated, customisable agents; embed the assessment process
      into a video game; or add narratives to encourage self-reporting behaviour. To
      improve accuracy, the intake environment could be recreated virtually; training
      sessions could be interspersed to improve portion estimation; and implicit
      attitudinal measures could be incorporated as a control or to increase validity.
      Research is needed to evaluate possible methods of enhancing children's self
      reporting motivation and accuracy. The main challenge remains how to engage
      children without biasing their reporting. 

PMID- 22594620
TI  - Informed consent for living donation: a review of key empirical studies, ethical
      challenges and future research.
AB  - Given the organ scarcity, live organ donation is increasingly considered a viable
      alternative for kidney and liver transplantation. Yet living donation challenges
      the ethical principle of nonmaleficence by subjecting healthy individuals to
      medical, psychosocial and unknown risks. Therefore, transplant providers, policy
      makers and donors are committed to ensuring that prospective donors provide
      adequate informed consent to undergo the procedure. Informed consent for living
      donation is ethically required as a means of demonstrating respect for donor's
      autonomy and protecting their safety. However, all elements of informed consent
      are fraught with difficulties due to the unique nature of the donation process
      and outcome. This paper reviews empirical research on informed consent for live
      kidney donors (LKD) and live liver donors (LLD) for both adult and pediatric
      recipients. As this review shows, studies that empirically assessed the quality
      of informed consent elements reveal considerable variability and deficiencies
      across the informed consent process, suggesting the need for improvement. This
      review highlights challenges to each element of consent for both LKDs and LLDs,
      and situates trends within broader policy contexts, ethical debates and avenues
      for future innovative research.

PMID- 22594619
TI  - Seasonal changes in the combined glucose-insulin tolerance test in normal aged
      horses.
AB  - BACKGROUND: Equine metabolic syndrome (EMS) is an increasingly recognized problem
      in adult horses. Affected horses are often obese and predisposed to the
      development of laminitis, especially in the spring and summer months. In
      addition, in the summer and fall months, increases in endogenous insulin
      concentrations, a marker of EMS, have been reported. HYPOTHESIS/OBJECTIVES: The
      purpose of this study was to evaluate seasonal changes in results of the combined
      glucose-insulin tolerance test (CGIT), a diagnostic test for EMS. ANIMALS: Nine
      healthy, aged horses with no history of laminitis and no clinical signs of EMS.
      METHODS: Horses were given dextrose (150 mg/kg) and insulin (0.1 U/kg) IV. Plasma
      glucose concentrations were measured at 0, 1, 5, 15, 30, 45, 60, 75, 90, and 150
      minutes and serum insulin concentrations at 0, 5, and 75 minutes. Testing was
      performed in February, May, June, August, September, and November. Mean glucose
      concentrations, characteristics of the curve, and insulin concentrations during
      the CGIT were compared across months using repeated measures ANOVA (P < .05).
      RESULTS: No CGIT parameters indicated insulin resistance, but mean area under the
      curve for glucose concentrations was significantly lower in August and November
      compared to February and in November compared to June, indicating increased
      insulin-mediated glucose clearance. Glucose nadir was significantly lower in
      November compared to that in February. CONCLUSIONS AND CLINICAL IMPORTANCE: No
      clinically relevant differences were seen in the results of the CGIT, suggesting
      that season minimally affects results of this test in normal aged horses in the
      southeastern United States.

PMID- 22594621
TI  - Heterogeneous kinetics of the carbon monoxide association and dissociation
      reaction to nitrophorin 4 and 7 coincide with structural heterogeneity of the
      gate-loop.
AB  - NO is an important signaling molecule in human tissue. However, the mechanisms by
      which this molecule is controlled and directed are currently little understood.
      Nitrophorins (NPs) comprise a group of ferriheme proteins originating from blood
      sucking insects that are tailored to protect and deliver NO via coordination to
      and release from the heme iron. Therefore, the kinetics of the association and
      dissociation reactions were studied in this work using the ferroheme-CO complexes
      of NP4, NP4(D30N), and NP7 as isoelectronic models for the ferriheme-NO
      complexes. The kinetic measurements performed by nanosecond laser-flash
      photolysis and stopped-flow are accompanied by resonance Raman and FT-IR
      spectroscopy to characterize the carbonyl species. Careful analysis of the CO
      rebinding kinetics reveals that in NP4 and, to a larger extent, NP7 internal gas
      binding cavities are located, which temporarily trap photodissociated ligands.
      Moreover, changes in the free energy barriers throughout the rebinding and
      release pathway upon increase of the pH are surprisingly small in case of NP4.
      Also in case of NP4, a heterogeneous kinetic trace is obtained at pH 7.5, which
      corresponds to the presence of two carbonyl species in the heme cavity that are
      seen in vibrational spectroscopy and that are due to the change of the distal
      heme pocket polarity. Quantification of the two species from FT-IR spectra
      allowed the fitting of the kinetic traces as two processes, corresponding to the
      previously reported open and closed conformation of the A-B and G-H loops. With
      the use of the A-B loop mutant NP4(D30N), it was confirmed that the kinetic
      heterogeneity is controlled by pH through the disruption of the H-bond between
      the Asp30 side chain and the Leu130 backbone carbonyl. Overall, this first study
      on the slow phase of the dynamics of diatomic gas molecule interaction with NPs
      comprises an important experimental contribution for the understanding of the
      dynamics involved in the binding/release processes of NO/CO in NPs.

PMID- 22594622
TI  - Development and myogenesis of the vermiform Buddenbrockia (Myxozoa) and
      implications for cnidarian body plan evolution.
AB  - BACKGROUND: The enigmatic wormlike parasite Buddenbrockia plumatellae has
      recently been shown to belong to the Myxozoa, which are now supported as a clade
      within Cnidaria. Most myxozoans are morphologically extremely simplified, lacking
      major metazoan features such as epithelial tissue layers, gut, nervous system,
      body axes and gonads. This hinders comparisons to free-living cnidarians and thus
      an understanding of myxozoan evolution and identification of their cnidarian
      sister group. However, B. plumatellae is less simplified than other myxozoans and
      therefore is of specific significance for such evolutionary considerations.
      METHODS: We analyse and describe the development of major body plan features in
      Buddenbrockia worms using a combination of histology, electron microscopy and
      confocal microscopy. RESULTS: Early developmental stages develop a primary body
      axis that shows a polarity, which is manifested as a gradient of tissue
      development, enabling distinction between the two worm tips. This polarity is
      maintained in adult worms, which, in addition, often develop a pore at the distal
      tip. The musculature comprises tetraradially arranged longitudinal muscle blocks
      consisting of independent myocytes embedded in the extracellular matrix between
      inner and outer epithelial tissue layers. The muscle fibres are obliquely
      oriented and in fully grown worms consistently form an angle of 12 degrees  with
      respect to the longitudinal axis of the worm in each muscle block and hence
      confer chirality. Connecting cells form a link between each muscle block and
      constitute four rows of cells that run in single file along the length of the
      worm. These connecting cells are remnants of the inner epithelial tissue layer
      and are anchored to the extracellular matrix. They are likely to have a
      biomechanical function. CONCLUSIONS: The polarised primary body axis represents
      an ancient feature present in the last common ancestor of Cnidaria and Bilateria.
      The tetraradial arrangement of musculature is consistent with a medusozoan
      affinity for Myxozoa. However, the chiral pattern of muscle fibre orientation is
      apparently novel within Cnidaria and could thus be a specific adaptation. The
      presence of independent myocytes instead of Cnidaria-like epitheliomuscular cells
      can be interpreted as further support for the presence of mesoderm in cnidarians,
      or it may represent convergent evolution to a bilaterian condition.

PMID- 22594623
TI  - Controlling silicon nanowire growth direction via surface chemistry.
AB  - We report on the first in situ chemical investigation of vapor-liquid-solid
      semiconductor nanowire growth and reveal the important, and previously
      unrecognized, role of transient surface chemistry near the triple-phase line.
      Real-time infrared spectroscopy measurements coupled with postgrowth electron
      microscopy demonstrate that covalently bonded hydrogen atoms are responsible for
      the (left angle bracket 111 right angle bracket) to (left angle bracket 112 right
      angle bracket) growth orientation transition commonly observed during Si nanowire
      growth. Our findings provide insight into the root cause of this well-known
      nanowire growth phenomenon and open a new route to rationally engineer the
      crystal structure of these nanoscale semi-conductors.

PMID- 22594624
TI  - LigMerge: a fast algorithm to generate models of novel potential ligands from
      sets of known binders.
AB  - One common practice in drug discovery is to optimize known or suspected ligands
      in order to improve binding affinity. In performing these optimizations, it is
      useful to look at as many known inhibitors as possible for guidance. Medicinal
      chemists often seek to improve potency by altering certain chemical moieties of
      known/endogenous ligands while retaining those critical for binding. To our
      knowledge, no automated, ligand-based algorithm exists for systematically
      'swapping' the chemical moieties of known ligands to generate novel ligands with
      potentially improved potency. To address this need, we have created a novel
      algorithm called 'LigMerge'. LigMerge identifies the maximum (largest) common
      substructure of two three-dimensional ligand models, superimposes these two
      substructures, and then systematically mixes and matches the distinct fragments
      attached to the common substructure at each common atom, thereby generating
      multiple compound models related to the known inhibitors that can be evaluated
      using computer docking prior to synthesis and experimental testing. To
      demonstrate the utility of LigMerge, we identify compounds predicted to inhibit
      peroxisome proliferator-activated receptor gamma, HIV reverse transcriptase, and
      dihydrofolate reductase with affinities higher than those of known ligands. We
      hope that LigMerge will be a helpful tool for the drug design community.

PMID- 22594626
TI  - Nanoporous TiO2/polyion thin-film-coated long-period grating sensors for the
      direct measurement of low-molecular-weight analytes.
AB  - We present novel nanoporous TiO(2)/polyion thin-film-coated long-period fiber
      grating (LPFG) sensors for the direct measurement of low-molecular-weight
      chemicals by monitoring the resonance wavelength shift. The hybrid overlay films
      are prepared by a simple layer-by-layer deposition approach, which is mainly
      based on the electrostatic interaction of TiO(2) nanoparticles and polyions. By
      the alternate immersion of LPFG into dispersions of TiO(2) nanoparticles and
      polyions, respectively, the so-formed TiO(2)/polyion thin film exhibits a unique
      nanoporous internal structure and has a relative higher refractive index than
      LPFG cladding. In particular, the porosity of the thin film reduces the diffusion
      coefficient and enhances the permeability retention of low-molecular-weight
      analytes within the porous film. The increases in the refractive index of the
      LPFG overlay results in a distinguished modulation of the resonance wavelength.
      Therefore, the detection sensitivity of LPFG sensors has been greatly improved,
      according to theoretical simulation. After the structure of the TiO(2)/polyion
      thin film was optimized, glucose solutions as an example with a low concentration
      of 10(-7) M was easily detected and monitored at room temperature.

PMID- 22594627
TI  - A vacuum-sealed miniature X-ray tube based on carbon nanotube field emitters.
AB  - A vacuum-sealed miniature X-ray tube based on a carbon nanotube field-emission
      electron source has been demonstrated. The diameter of the X-ray tube is 10 mm;
      the total length of the tube is 50 mm, and no external vacuum pump is required
      for the operation. The maximum tube voltage reaches up to 70 kV, and the X-ray
      tube generates intense X-rays with the air kerma strength of 108 Gy.cm2 min-1. In
      addition, X-rays produced from the miniature X-ray tube have a comparatively
      uniform spatial dose distribution.

PMID- 22594628
TI  - Pathophysiologies of dyspnea explained: why might opioids relieve dyspnea and not
      hasten death?

PMID- 22594629
TI  - A multiparent advanced generation inter-cross population for genetic analysis in
      wheat.
AB  - We present the first results from a novel multiparent advanced generation inter
      cross (MAGIC) population derived from four elite wheat cultivars. The large size
      of this MAGIC population (1579 progeny), its diverse genetic composition and high
      levels of recombination all contribute to its value as a genetic resource.
      Applications of this resource include interrogation of the wheat genome and the
      analysis of gene-trait association in agronomically important wheat phenotypes.
      Here, we report the utilization of a MAGIC population for the first time for
      linkage map construction. We have constructed a linkage map with 1162 DArT,
      single nucleotide polymorphism and simple sequence repeat markers distributed
      across all 21 chromosomes. We benchmark this map against a high-density DArT
      consensus map created by integrating more than 100 biparental populations. The
      linkage map forms the basis for further exploration of the genetic architecture
      within the population, including characterization of linkage disequilibrium,
      founder contribution and inclusion of an alien introgression into the genetic
      map. Finally, we demonstrate the application of the resource for quantitative
      trait loci mapping using the complex traits plant height and hectolitre weight as
      a proof of principle.

PMID- 22594630
TI  - Factors related to respiration influencing survival and respiratory function in
      patients with amyotrophic lateral sclerosis: a retrospective study.
AB  - BACKGROUND: Various breathing abnormalities (Neurology 2009; 73: 1218) have been
      proposed as indicators for the introduction of non-invasive positive-pressure
      ventilation (NIV) in patients with amyotrophic lateral sclerosis (ALS). We were
      interested in the usefulness of symptoms of respiratory insufficiency and
      abnormal results of daytime arterial gas analyses (AGA) as predictors of survival
      and the effect of NIV on respiratory volumes and pressures. METHODS: Reported
      symptoms, respiratory subscore of the ALS Functional Rating Scale (ALSFRS-r),
      Norris scale (Norris-r), and AGA were retrospectively analyzed in 189 ALS
      patients. Longitudinal follow-up of forced vital capacity (FVC), maximal
      inspiratory and expiratory pressure (MIP, MEP), and sniff nasal pressure (SNP)
      were analyzed with regard to the introduction of NIV. RESULTS: Respiratory
      symptoms were a bad prognostic sign (P = 0.007). Abnormalities in Norris-r,
      ALSFRS-r, pO(2), pCO(2), and oxygen saturation tended to be associated with a
      shorter survival, although they were not statistically significant. NIV prolonged
      survival and reduced the decline in FVC (P = 0.007), MIP, MEP, and SNP (the last
      three were not statistically significant). Symptoms, abnormal FVC, and AGA do not
      always coincide, and they can appear in a different sequence. CONCLUSIONS: Any
      respiratory abnormality should prompt the clinician to start discussing NIV with
      the patient. NIV prolongs survival and improves respiratory function.

PMID- 22594631
TI  - Older adults' beliefs about the timeline of type 2 diabetes and adherence to
      dietary regimens.
AB  - The common-sense model posits that behavioural coping with illness is shaped by a
      complex combination of individuals' abstract and concrete beliefs about their
      illness. We investigated this theoretical assumption in a study of 116 older
      adults diagnosed with type 2 diabetes who completed in-person interviews at
      baseline and six and 12 months later. Specifically, we examined (1) the
      interaction of patients' abstract and concrete beliefs about the timeline of
      their diabetes as a predictor of change in adherence to a healthy diet and (2)
      whether these interactive effects differ among male and female patients. Abstract
      timeline beliefs were conceptualised as those pertaining to disease duration;
      concrete timeline beliefs were conceptualised as those pertaining to variability
      of disease symptoms (i.e. symptoms are stable versus fluctuating). As predicted,
      duration beliefs were positively associated with improvement in adherence among
      patients who viewed disease symptoms as stable, but not among those who viewed
      symptoms as variable. When gender was considered, these interactive effects were
      observed among male (but not female) patients. Findings revealed that the
      behavioural effects of men's abstract knowledge about their diabetes were
      conditioned by their concrete representations of the disease, suggesting a bottom
      up process of influence with implications for intervention.

PMID- 22594632
TI  - Is primary open-angle glaucoma part of a generalized sensory neurodegeneration? A
      review of the evidence.
AB  - Open-angle glaucoma is an optic neuropathy that has a multifarious aetiological
      profile. Emerging theories suggest that a group of factors induce optic nerve
      injury in innately susceptible aging optic nerves. These factors have the
      potential to impact on the function of other vulnerable neurons within the
      central nervous system of older patients. Although changes within the visual
      pathways due to retinal ganglion cell dysfunction and death are well established,
      research exploring the behaviour of other sensory systems in individuals with
      glaucoma is limited. This review summarizes what is known about these other non
      visual sensory changes, explores whether glaucoma is in fact part of a global
      neurodegenerative condition, and suggests areas for future research direction.

PMID- 22594633
TI  - Quantile uncertainty and value-at-risk model risk.
AB  - This article develops a methodology for quantifying model risk in quantile risk
      estimates. The application of quantile estimates to risk assessment has become
      common practice in many disciplines, including hydrology, climate change,
      statistical process control, insurance and actuarial science, and the uncertainty
      surrounding these estimates has long been recognized. Our work is particularly
      important in finance, where quantile estimates (called Value-at-Risk) have been
      the cornerstone of banking risk management since the mid 1980s. A recent
      amendment to the Basel II Accord recommends additional market risk capital to
      cover all sources of "model risk" in the estimation of these quantiles. We
      provide a novel and elegant framework whereby quantile estimates are adjusted for
      model risk, relative to a benchmark which represents the state of knowledge of
      the authority that is responsible for model risk. A simulation experiment in
      which the degree of model risk is controlled illustrates how to quantify Value-at
      Risk model risk and compute the required regulatory capital add-on for banks. An
      empirical example based on real data shows how the methodology can be put into
      practice, using only two time series (daily Value-at-Risk and daily profit and
      loss) from a large bank. We conclude with a discussion of potential applications
      to nonfinancial risks.

PMID- 22594634
TI  - Commentary on Wagener et al. (2012): E-cigarettes: room for cautious optimism.

PMID- 22594635
TI  - Cell-penetrating peptides for the delivery of nucleic acids.
AB  - INTRODUCTION: Different gene therapy approaches have gained extensive interest
      lately and, after many initial hurdles, several promising approaches have reached
      to the clinics. Successful implementation of gene therapy is heavily relying on
      finding efficient measures to deliver genetic material to cells. Recently, non
      viral delivery of nucleic acids and their analogs has gained significant
      interest. Among non-viral vectors, cell-penetrating peptides (CPPs) have been
      extensively used for the delivery of nucleic acids both in vitro and in vivo.
      AREAS COVERED: In this review we will discuss recent advances of CPP-mediated
      delivery of nucleic acid-based cargo, concentrating on the delivery of plasmid
      DNA, splice-correcting ONs, and small-interfering RNAs. EXPERT OPINION: CPPs have
      proved their potential as carriers for nucleic acids. However, similarly to other
      non-viral vectors, CPPs require further development, as efficient systemic
      delivery is still seldom achieved. To achieve this, CPPs should be modified with
      entities that would allow better endosomal escape, targeting of specific tissues
      and cells, and shielding agents that increase the half-life of the vehicles.
      Finally, to understand the clinical potential of CPPs, they require more thorough
      investigations in clinically relevant disease models and in pre-clinical and
      clinical studies.

PMID- 22594636
TI  - Immobilization of laccase on polyacrylamide and polyacrylamide - kappa -
      carragennan-based semi-interpenetrating polymer networks.
AB  - In this study, laccase enzyme (L) from Agaricus bisporus was immobilized by
      entrapment into polyacrylamide (PAAm) and semi-interpenetrating polymer networks
      (semi-IPNs) prepared with either polyacrylamide/kappa-carragennan (0.05g) [PAAm/
      kappa-car (0.05)] or polyacrylamide/kappa-carragennan (0.1 g) [PAAm/ kappa-car
      (0.1)]. The optimum pH was 6.0 for free L, 8.0 for PAAm-L, 8.5 for PAAm/kappa-car
      (0.05)-L, and 9.0 for PAAm/kappa-car (0.1)-L. The optimum temperature was
      determined as 45 degrees C for free L and 60 degrees C for all immobilized
      laccases. After 27 days of storage at 4 degrees C, free enzyme lost its initial
      activity whereas immobilized enzymes retained 56 % (-)80% of their initial
      activities. The immobilized samples were used repeatedly 35 times by retaining 28
      %-58 % of their initial activity. K(m(app)) values were calculated as 0.088,
      0.139, 0.133, and 0.131 mM and Vmax values were found to be 2.83 x 10(-3),
      4.51*10(-3), 4.76*10(-3), and 4.97*10(-3) mM min(-1) for free L and PAAm-L,
      PAAm/kappa-car (0.05)-L, and PAAm/kappa-car (0.1)-L, respectively.

PMID- 22594637
TI  - Serum pepsinogen-A, canine pancreatic lipase immunoreactivity, and C-reactive
      protein as prognostic markers in dogs with gastric dilatation-volvulus.
AB  - BACKGROUND: Pepsinogens are proenzymes secreted by gastric chief cells. In
      humans, their serum concentrations reflect gastric mucosal morphological and
      functional status. OBJECTIVES: To evaluate serum canine pepsinogen-A (cPG-A), C
      reactive protein (CRP), and canine pancreatic lipase immunoreactivity (cPLI)
      concentrations in dogs with gastric dilatation-volvulus (GDV). ANIMALS: Sixty-six
      dogs presented with GDV and 79 healthy controls. METHODS: Blood was collected
      prospectively, and records retrospectively reviewed. RESULTS: Median cPG-A
      concentration was higher in GDV dogs (median, 397 MUg/L; range, 37-5,410)
      compared to controls (median, cPG-A 304 MUg/L; range, 18-848; P = .07). Mortality
      rate in GDV dogs was 22.7%. In nonsurvivors of GDV, median cPG-A was higher
      compared to survivors (median, 746 MUg/L; range, 128-5,409 versus median, 346;
      range, 36-1,575, respectively; P = .003). The proportion of dogs with increased
      cPG-A increased with gastric wall damage score (P = .007). An ROC analysis of cPG
      A as a predictor of death showed an area under the curve (AUC) of 0.75, higher
      than lactate (AUC 0.66), and corresponded to a sensitivity and specificity of 53%
      and 88%, respectively. CRP was increased in 48 dogs (75%), cPLI was >200 MUg/L in
      26 dogs (39.4%) and >400 MUg/L in 12 dogs (18.2%) but both analytes had no
      association with outcome. CONCLUSIONS: Presurgical cPG-A concentration was
      positively and significantly associated with gastric wall lesion severity, but,
      based on ROC analysis, it was only a moderate outcome predictor. CRP and cPLI
      were commonly increased in dogs with GDV.

PMID- 22594638
TI  - As(III) oxidation by active chlorine and subsequent removal of As(V) by Al13
      polymer coagulation using a novel dual function reagent.
AB  - An electrochemically prepared water treatment reagent containing a high
      concentration of Al(13) polymer and active chlorine (PACC) showed promising
      potential for the removal of As(III) due to the combined function of oxidation
      and coagulation. The results indicated that PACC was effective for As(III)
      removal through oxidation by the active chlorine and subsequent removal of As(V)
      by coagulation with the Al(13) polymer. The As(III) was oxidized to As(V) by
      active chlorine in PACC, with a stoichiometric rate of 0.99 mg Cl(2)/mg As(III).
      The Al(13) polymer was the most active Al species responsible for As(V) removal
      in PACC. To meet As drinking water standards the stoichiometric weight ratio of
      Cl(2)/Al within PACC was 0.09 for the treatment of As(III). Considering the
      process of As(III) oxidation and As(V) coagulation together, the optimal pH
      conditions for the removal of As by PACC was within the neutral range, which
      facilitated the reaction of As(III) with active chlorine and favored the
      formation of Al hydroxide flocs. The presence of humic acid reduced the As(III)
      removal efficiency of PACC due to its negative influence on subsequent As(V)
      coagulation, and disinfection byproduct yields were very low in the presence of
      insufficient or stoichiometric active chlorine.

PMID- 22594639
TI  - Discovery of novel Bruton's tyrosine kinase inhibitors using a hybrid protocol of
      virtual screening approaches based on SVM model, pharmacophore and molecular
      docking.
AB  - Bruton's tyrosine kinase has emerged as a potential target for the treatment for
      B-cell malignancies and autoimmune diseases. Discovery of Bruton's tyrosine
      kinase inhibitors has thus attracted much attention recently. In this
      investigation, we introduced a hybrid protocol of virtual screening methods
      including support vector machine model-based virtual screening, pharmacophore
      model-based virtual screening and docking-based virtual screening for retrieving
      new Bruton's tyrosine kinase inhibitors from commercially available chemical
      databases. Performances of the hybrid virtual screening approach were evaluated
      against a test set, which results showed that the hybrid virtual screening
      approach significantly shortened the overall screening time, and considerably
      increased the hit rate and enrichment factor compared with the individual method
      (SB-VS, PB-VS and DB-VS) or their combinations by twos. This hybrid virtual
      screening approach was then applied to screen several chemical databases
      including Specs (202,408 compounds) and Enamine (980,000 compounds) databases.
      Thirty-nine compounds were selected from the final hits and have been shifted to
      experimental studies.

PMID- 22594640
TI  - Fluorescent and highly stable unimodal DMPC based unilamellar vesicles formed by
      spontaneous curvature.
AB  - The formation of uniform and highly stable unilamellar vesicles (ULVs) and the
      theory behind it are ongoing tasks within the vesicle community. Herein, we
      report the formation of highly stable, fluorescent, and unimodal 1,2-dimyristoyl
      sn-glycero-3-phosphocholine (DMPC) based ULVs with an average size of ~100 nm, as
      determined by cryogenic transmission electron microscopy (cryo-TEM) and dynamic
      light scattering (DLS). The ULVs are formed by mixing a two-component powder
      mixture or mixed lipid film of DMPC and 5 mol % of a novel amphiphilic carbenium
      salt, sodium 2-didecylamino-6,10-bis(N-methyltaruino)-4,8,12-trioxatriangulenium
      (Na-DSA) in aqueous solution when subjected to shaking. We propose that the high
      stability and the unimodal size distribution of the 5% DSA ULVs confirmed by DLS
      studies are a product of spontaneous curvature. UV-vis absorption/emission
      studies reveal that the structure of DSA promotes a strong interaction between
      the DMPC and the DSA to take place due to the complementary charge distribution
      of the DSA and DMPC head groups. The strong interaction may introduce an
      asymmetric amphiphile composition in the inner and outer leaflet of the bilayer
      which drives the spontaneous curvature.

PMID- 22594642
TI  - Nationwide integrated mapping of three neglected tropical diseases in Togo:
      countrywide implementation of a novel approach.
AB  - OBJECTIVE: To conduct a nationwide integrated neglected tropical disease (NTD)
      prevalence survey to define the need for public health interventions using an
      innovative mapping protocol. METHODS: Two villages were selected in every
      peripheral health unit in endemic districts: 29 districts for schistosomiasis and
      STH, 15 of them for trachoma. In each village, 15 children aged 6-9 years at a
      randomly selected school were tested. An additional convenience sample of 35
      children aged 1-5 years underwent an eye examination for trachoma. This
      integrated mapping was followed by a 20-cluster trachoma survey in each district
      that surpassed the WHO-defined threshold of 10% prevalence of trachomatous
      inflammation-follicular (TF). RESULTS: A total of 1096 villages were surveyed in
      <6 weeks. The district prevalence of schistosomiasis ranged from 2 to 49% and of
      STH from 5 to 70%, with prevalence at the village level ranging from 0 to 100%
      for both diseases. Two districts passed the threshold of 10% for active trachoma,
      but the cluster survey indicated this was because of misclassification bias and
      that the real prevalence was <1%. CONCLUSION: Results of this mapping were used
      by the MoH and partners to plan integrated mass drug administration (MDA). Mass
      drug administration for trachoma was not implemented as no district passed the
      threshold requiring public health intervention.

PMID- 22594641
TI  - Ion pair reinforced semi-interpenetrating polymer network for direct methanol
      fuel cell applications.
AB  - This paper describes the synthesis of ion-pair-reinforced semi-interpenetrating
      polymer networks (SIPNs) as proton exchange membranes (PEMs) for the direct
      methanol fuel cells (DMFCs). Specifically, sulfonated poly(2,6-dimethyl-1,4
      phenylene oxide) (SPPO), a linear polymer proton source, was immobilized in a
      brominated PPO (BPPO) network covalently cross-linked by ethylenediamine (EDA).
      The immobilization of SPPO in the SIPN network was accomplished not only by the
      usual means of mechanical interlocking but also by ion pair formation between the
      sulfonic acid groups of SPPO and the amine moieties formed during the cross
      linking reaction of BPPO with EDA. Through the ion pair interactions, the
      immobilization of SPPO polymer in the BPPO network was made more effective,
      resulting in a greater uniformity of sulfonic acid cluster distribution in the
      membrane. The hydrophilic amine-containing cross-links also compensated for some
      of the decrease in proton conductivity caused by ion pair formation. The SIPN
      membranes prepared as such showed good proton conductivity, low methanol
      permeability, good mechanical properties, and dimensional stability.
      Consequently, the PPO based SIPN membranes were able to deliver a higher maximum
      power density than Nafion, demonstrating the potential of the SIPN structure for
      PEM designs.

PMID- 22594643
TI  - Conceptualizing in plant pathology.

PMID- 22594644
TI  - Multifunctional devices and logic gates with undoped silicon nanowires.
AB  - We report on the electronic transport properties of multiple-gate devices
      fabricated from undoped silicon nanowires. Understanding and control of the
      relevant transport mechanisms was achieved by means of local electrostatic gating
      and temperature-dependent measurements. The roles of the source/drain contacts
      and of the silicon channel could be independently evaluated and tuned. Wrap gates
      surrounding the silicide-silicon contact interfaces were proved to be effective
      in inducing a full suppression of the contact Schottky barriers, thereby enabling
      carrier injection down to liquid helium temperature. By independently tuning the
      effective Schottky barrier heights, a variety of reconfigurable device
      functionalities could be obtained. In particular, the same nanowire device could
      be configured to work as a Schottky barrier transistor, a Schottky diode, or a p
      n diode with tunable polarities. This versatility was eventually exploited to
      realize a NAND logic gate with gain well above one.

PMID- 22594645
TI  - Successful organ donation after long-term circulatory support with nonpulsatile
      mechanical support.

PMID- 22594646
TI  - Common variants in mismatch repair genes associated with increased risk of sperm
      DNA damage and male infertility.
AB  - BACKGROUND: The mismatch repair (MMR) pathway plays an important role in the
      maintenance of the genome integrity, meiotic recombination and gametogenesis.
      This study investigated whether genetic variations in MMR genes are associated
      with an increased risk of sperm DNA damage and male infertility. METHODS: We
      selected and genotyped 21 tagging single nucleotide polymorphisms (SNPs) in five
      MMR genes (MLH1, MLH3, PMS2, MSH4 and MSH5) using the SNPstream 12-plex platform
      in a case-control study of 1,292 idiopathic infertility patients and 480 fertile
      controls in a Chinese population. Sperm DNA damage levels were detected with the
      Tdt-mediated dUTP nick end labelling (TUNEL) assay in 450 cases. Fluorescence
      resonance energy transfer (FRET) and co-immunoprecipitation techniques were
      employed to determine the effects of functional variants. RESULTS: One intronic
      SNP in MLH1 (rs4647269) and two non-synonymous SNPs in PMS2 (rs1059060,
      Ser775Asn) and MSH5 (rs2075789, Pro29Ser) seem to be risk factors for the
      development of azoospermia or oligozoospermia. Meanwhile, we also identified a
      possible contribution of PMS2 rs1059060 to the risk of male infertility with
      normal sperm count. Among patients with normal sperm count, MLH1 rs4647269 and
      PMS2 rs1059060 were associated with increased sperm DNA damage. Functional
      analysis revealed that the PMS2 rs1059060 can affect the interactions between
      MLH1 and PMS2. CONCLUSIONS: Our results provide evidence supporting the
      involvement of genetic polymorphisms in MMR genes in the aetiology of male
      infertility.

PMID- 22594647
TI  - Effect of cediranib, an inhibitor of vascular endothelial growth factor receptor
      tyrosine kinase, in a mouse model of choroidal neovascularization.
AB  - BACKGROUND: This study was conducted to evaluate the effect of cediranib, an
      inhibitor of vascular endothelial growth factor receptor tyrosine kinase, in a
      mouse model of laser-induced choroidal neovascularization. METHODS: Choroidal
      neovascularization was induced in C57BL/6 mice by rupturing Bruch's membrane
      using laser photocoagulation. Following laser injury, the mice were divided into
      three groups and administered either vehicle, 1 mg/kg or 5 mg/kg of cediranib
      daily by oral gavage for 2 weeks. Two weeks after laser injury, the area of
      choroidal neovascularization lesions was measured by choroidal flat mounts using
      fluorescein-labelled dextran. Immunofluorescence staining with isolectin IB4 was
      also used to quantify the choroidal neovascularization lesions. RESULTS:
      Choroidal flat mount analysis revealed that orally administered cediranib reduced
      the extent of choroidal neovascularization. The groups treated with 1 and 5
      mg/kg/day showed 57.2 and 66.0% reduction of choroidal neovascularization
      lesions, respectively, compared with the control group treated with vehicle alone
      (P = 0.012). The size of the fluorescently labelled choroidal neovascularization
      complex in cediranib-treated groups was much smaller than that from vehicle
      treated group (P = 0.035). CONCLUSIONS: Cediranib inhibited laser-induced
      choroidal neovascularization in mice and may have therapeutic potential for
      patients with neovascular age-related macular degeneration.

PMID- 22594648
TI  - Multiweek resting EEG cordance change patterns from repeated olfactory activation
      with two constitutionally salient homeopathic remedies in healthy young adults.
AB  - OBJECTIVES: Electroencephalography (EEG) offers psychophysiologic tools to
      improve sensitivity for detecting objective effects in complementary and
      alternative medicine. This current investigation extended prior clinical research
      studies to evaluate effects of one of two different homeopathic remedies on
      resting EEG cordance after an olfactory activation protocol on healthy young
      adults with remedy-relevant, self-perceived characteristics. METHODS: Ninety
      seven (7) young adults (N=97, mean age 19 years, 55% women) with good self-rated
      global health and screened for homeopathic constitutional types consistent with
      one of two remedies (either Sulphur or Pulsatilla) underwent three weekly
      laboratory sessions. At each visit, subjects had 5-minute resting, eyes-closed
      EEG recordings before and after a placebo-controlled olfactory activation task
      with their constitutionally relevant verum remedy. One remedy potency (6c, 12c,
      or 30c) used per week, was presented in a randomized order over the 3 sessions.
      Prefrontal resting EEG cordance values at Fp1 and Fp2 were computed from artifact
      free 2-minute EEG samples from the presniffing and postsniffing rest periods.
      Cordance derives from an algorithm that incorporates absolute and relative EEG
      values. RESULTS: The data showed significant two-way oscillatory interactions of
      remedy by time for beta, alpha, theta, and delta cordance, controlling for gender
      and chemical sensitivity. CONCLUSIONS: EEG cordance provided a minimally invasive
      technique for assessing objective nonlinear physiologic effects of two different
      homeopathic remedies salient to the individuals who received them. Time factors
      modulated the direction of effects. Given previous evidence of correlations
      between cordance and single-photon emission computed tomography, these findings
      encourage additional neuroimaging research on nonlinear psychophysiologic effects
      of specific homeopathic remedies.

PMID- 22594649
TI  - Anti-inflammatory effect of Keigai-rengyo-to extract and acupuncture in male
      patients with acne vulgaris: a randomized controlled pilot trial.
AB  - OBJECTIVES: The objectives of this study were to evaluate the efficacy and
      interaction of Keigai-rengyo-to extract (KRTE) and acupuncture in male patients
      with acne and the feasibility of a large clinical trial. DESIGN: A randomized,
      assessor single-blinded, 2*2 factorial trial was conducted. The trial is
      registered with the Clinical Research Information Service, Republic of Korea:
      KCT0000071. SUBJECTS: Forty-four (44) participants with acne vulgaris were
      randomized into one of four groups: waiting list group (WL), KRTE only group
      (KO), acupuncture only group (AO), and KRTE and acupuncture combined treatment
      group (KA). INTERVENTION: After randomization, patients in the AO and KA groups
      underwent eight sessions of acupuncture treatment, twice per week. Patients in
      the KO and KA groups were prescribed KRTE 3 times daily, 7.4 g each dose, after
      meals, for 4 weeks. OUTCOME MEASURES: The following outcome measurements were
      used in examination of subjects: mean percentage change and the count change of
      inflammatory and noninflammatory acne lesions, Skindex 29, investigator global
      assessment from baseline to end of trial, and proportion of dropouts and
      compliance with KRTE. RESULTS: A significant interaction of KRTE and acupuncture
      was evident according to mean percent change of inflammatory acne lesions, but
      not of noninflammatory acne lesions from baseline to the end of the study.
      Statistically significant differences were observed in the primary effect on mean
      percent change of noninflammatory acne lesions, not by acupuncture, but by KRTE.
      Adjusted Skindex 29 score changes indicated no statistically significant
      reduction within groups and between groups. The improvement rate in patients with
      KRTE and acupuncture treatment was not significant, compared to patients with no
      KRTE and acupuncture treatment. The proportion of dropouts was 22.7% and rate of
      compliance with KRTE was 92.3%. CONCLUSIONS: For treatment of acne vulgaris, use
      of KRTE combined with acupuncture is recommended for inflammatory lesions and
      KRTE only is recommended for noninflammatory lesions. Further large-scale trials
      assuming a higher dropout rate and aimed at confirming the ability of KRTE and
      acupuncture to improve inflammatory and noninflammatory lesions in patients with
      acne are needed.

PMID- 22594650
TI  - The relationship between maximal exercise-induced increases in serum IL-6, MPO
      and MMP-9 concentrations.
AB  - The aim of this study was to test the hypothesis that exercise would induce
      inflammatory response characterized by increased pro-inflammatory cytokines -
      interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha), adhesion
      molecule, matrix metalloprotease-9 (MMP-9) and myeloperoxidase (MPO) levels.
      Additional aim was to elucidate the possible source of maximal exercise-induced
      increase in MMP-9 concentration. To examine our hypothesis, 26 professional male
      ice hockey players [age 25 +/- 1 (mean +/- SEM) years; BMI 25.8 +/- 0.4 kg/m(2) ]
      performed an incremental bicycle test until exhaustion, when maximal oxygen
      consumption was recorded. Venous blood samples were collected 30 min before and 2
      min after exercise. There was an increase in the count of leucocytes (8.7 +/- 1.8
      versus 5.7 +/- 1.3 * 10(9) cells per l) and IL-6 (1.24 +/- 0.17 versus 0.69 +/-
      0.13 pg/ml), MPO (72 +/- 7 versus 50 +/- 4 ng/ml) and MPP-9 (139 +/- 9 versus 110
      +/- 6 ng/ml) concentrations (P < 0.05) comparing post- and pre-exercise levels.
      Maximal exercise-induced increase in MPO correlated with the increases in IL-6 (P
      < 0.05, R = 0.54) and MMP-9 (P < 0.01, R = 0.62) concentrations. Furthermore,
      increase in IL-6 correlated with the increase in MMP-9 concentrations (P < 0.05,
      R = 0.60). Maximal exercise induces an inflammatory response characterized by
      leucocytosis and increased IL-6, MPO and MMP-9 concentrations. Correlations
      between increased MPO (marker of neutrophils degranulation) and both increased IL
      6 and MMP-9 concentrations may suggest that neutrophils could be the main source
      of these inflammatory biomarkers during maximal exercise. Furthermore,
      correlation between increases in serum IL-6 and MMP-9 concentrations may suggest
      that IL-6 could exert modulatory effects on MMP-9 release during maximal
      exercise.

PMID- 22594651
TI  - The combined effect of very low nicotine content cigarettes, used as an adjunct
      to usual Quitline care (nicotine replacement therapy and behavioural support), on
      smoking cessation: a randomized controlled trial.
AB  - AIM: To determine the combined effect of very low nicotine content (VLNC)
      cigarettes and usual Quitline care [nicotine replacement therapy (NRT) and
      behavioural support] on smoking abstinence, in smokers motivated to quit. DESIGN:
      Single-blind, parallel randomized trial. SETTING: New Zealand. PARTICIPANTS
      Smokers who called the Quitline for quitting support were randomized to either
      VLNC cigarettes to use whenever they had an urge to smoke for up to 6 weeks after
      their quit date, in combination with usual Quitline care (8 weeks of NRT patches
      and/or gum or lozenges, plus behavioural support) or to usual Quitline care
      alone. MEASUREMENTS: The primary outcome was 7-day point-prevalence smoking
      abstinence 6 months after quit day. Secondary outcomes included continuous
      abstinence, cigarette consumption, withdrawal, self-efficacy, alcohol use,
      serious adverse events and views on the use of the VLNC cigarettes at 3 and 6
      weeks and 3 and 6 months. FINDINGS: A total of 1410 participants were randomized
      (705 in each arm), with a 24% loss to follow-up at 6 months. Participants in the
      intervention group were more likely to have quit smoking at 6 months compared to
      the usual care group [7-day point-prevalence abstinence 33 versus 28%, relative
      risk (RR) = 1.18, 95% confidence interval (CI): 1.01, 1.39, P = 0.037; continuous
      abstinence 23 versus 15%, RR = 1.50, 95% CI: 1.20, 1.87, P = 0.0003]. The median
      time to relapse in the intervention group was 2 months compared to 2 weeks in the
      usual care group (P < 0.0001). CONCLUSIONS: Addition of very low nicotine content
      cigarettes to standard Quitline smoking cessation support may help some smokers
      to become abstinent.

PMID- 22594652
TI  - Diverse functional responses to drought in a Mediterranean-type shrubland in
      South Africa.
AB  - * Mediterranean-type ecosystems contain 20% of all vascular plant diversity on
      Earth and have been identified as being particularly threatened by future
      increases in drought. Of particular concern is the Cape Floral Region of South
      Africa, a global biodiversity hotspot, yet there are limited experimental data to
      validate predicted impacts on the flora. In a field rainout experiment, we tested
      whether rooting depth and degree of isohydry or anisohydry could aid in the
      functional classification of drought responses across diverse growth forms. * We
      imposed a 6-month summer drought, for 2 yr, in a mountain fynbos shrubland. We
      monitored a suite of parameters, from physiological traits to morphological
      outcomes, in seven species comprising the three dominant growth forms (deep
      rooted proteoid shrubs, shallow-rooted ericoid shrubs and graminoid restioids). *
      There was considerable variation in drought response both between and within the
      growth forms. The shallow-rooted, anisohydric ericoid shrubs all suffered
      considerable reductions in growth and flowering and increased mortality. By
      contrast, the shallow-rooted, isohydric restioids and deep-rooted, isohydric
      proteoid shrubs were largely unaffected by the drought. * Rooting depth and
      degree of iso/anisohydry allow a first-order functional classification of drought
      response pathways in this flora. Consideration of additional traits would further
      refine this approach.

PMID- 22594653
TI  - Effect of heart failure on dipeptidyl peptidase IV activity in plasma of dogs.
AB  - BACKGROUND: In congestive heart failure (HF), plasma B-type natriuretic peptide
      (BNP) seems devoid of biological effectiveness. BNP(1-32) could be truncated into
      BNP(3-32) by dipeptidyl peptidase IV (DPP4), and BNP(3-32) has reduced biological
      activities. HYPOTHESIS: Increased DPP4 activity is associated with
      pathophysiology of HF. ANIMALS: One hundred twenty-eight client-owned dogs and 9
      experimental Beagles from the Clinical Veterinary Unit of the University of
      Liege. METHODS: We prospectively measured plasma DPP4 activity in 5 groups of
      dogs: normal growing dogs (n = 21), normal adult dogs (n = 60), healthy Beagle (n
      = 9), dogs with myxomatous mitral valve disease (n = 35), and dogs with dilated
      cardiomyopathy (n = 12). The final diagnosis and the severity of HF were
      determined by Doppler echocardiography. Plasma DPP4 activity was measured
      kinetically by a fluorimetric method. RESULTS: In growing dogs, DPP4 activity was
      higher than in adults (P < .001) and inversely correlated with age (r = -0.57, P
      < .01). In adults, DPP4 activity increased linearly with body weight (r = 0.39, P
      < .01), but there was no influence of age or sex. No effect of the circadian
      rhythm was noted. DPP4 activity was significantly higher in HF ISACHC I (16.3 +/-
      1.14 U/L) compared with healthy adults (12.4 +/- 0.65 U/L, P < .05) and HF ISACHC
      III (11.0 +/- 1.50 U/L, P < .05). Mean DPP4 activity in ISACHC II was 15.1 +/-
      1.4 U/L. CONCLUSION AND CLINICAL IMPORTANCE: We did not find evidence that plasma
      DPP4 activity is responsible for the "BNP resistance" in overt congestive HF, but
      it may be implicated in early stages.

PMID- 22594654
TI  - From mosaic to patchwork: matching lipids and proteins in membrane organization.
AB  - Biological membranes encompass and compartmentalize cells and organelles and are
      a prerequisite to life as we know it. One defining feature of membranes is an
      astonishing diversity of building blocks. The mechanisms and principles
      organizing the thousands of proteins and lipids that make up membrane bilayers in
      cells are still under debate. Many terms and mechanisms have been introduced over
      the years to account for certain phenomena and aspects of membrane organization
      and function. Recently, the different viewpoints - focusing on lipids vs.
      proteins or physical vs. molecular driving forces for membrane organization - are
      increasingly converging. Here we review the basic properties of biological
      membranes and the most common theories for lateral segregation of membrane
      components before discussing an emerging model of a self-organized, multi-domain
      membrane or 'patchwork membrane'.

PMID- 22594655
TI  - Rationalizing nanomaterial sizes measured by atomic force microscopy, flow field
      flow fractionation, and dynamic light scattering: sample preparation,
      polydispersity, and particle structure.
AB  - This study aims to rationalize the variability in the measured size of
      nanomaterials (NMs) by some of the most commonly applied techniques in the field
      of nano(eco)toxicology and environmental sciences, including atomic force
      microscopy (AFM), dynamic light scattering (DLS), and flow field-flow
      fractionation (FlFFF). A validated sample preparation procedure for size
      evaluation by AFM is presented, along with a quantitative explanation of the
      variability of measured sizes by FlFFF, AFM, and DLS. The ratio of the z-average
      hydrodynamic diameter (d(DLS)) by DLS and the particle height by AFM (d(AFM))
      approaches 1.0 for monodisperse samples and increases with sample polydispersity.
      A polydispersity index of 0.1 is suggested as a suitable limit above which DLS
      data can no longer be interpreted accurately. Conversion of the volume particle
      size distribution (PSD) by FlFFF-UV to the number PSD reduces the differences
      observed between the sizes measured by FlFFF (d(FlFFF)) and AFM. The remaining
      differences in the measured sizes can be attributed to particle structure
      (sphericity and permeability). The ratio d(FlFFF)/d(AFM) approaches 1 for small
      ion-coated NMs, which can be described as hard spheres, whereas d(FlFFF)/d(AFM)
      deviates from 1 for polymer-coated NMs, indicating that these particles are
      permeable, nonspherical, or both. These findings improve our understanding of the
      rather scattered data on NM size measurements reported in the environmental and
      nano(eco)toxicology literature and provide a tool for comparison of the measured
      sizes by different techniques.

PMID- 22594656
TI  - The effects of alcohol on the metabolism and toxicology of anti-psoriasis drugs.
AB  - INTRODUCTION: Alcohol has long been suspected to be a triggering and
      precipitating factor of psoriasis. Alcohol misuse is common in patients with
      moderate-to-severe psoriasis and appears to impair treatment outcome. AREAS
      COVERED: In this article, the authors review the available data regarding the
      metabolic and toxicological interactions between anti-psoriasis systemic drugs
      and ethanol and/or alcoholic beverages. Special attention is given to the
      influence of alcohol consumption on the hepatotoxic risk of some anti-psoriasis
      drugs. The article was prepared using a MEDLINE literature search. EXPERT
      OPINION: The available knowledge highlights the existence of a few significant
      pharmacological interactions, such as the reduced exposure to cyclosporine by red
      wine, the possible increase of cyclosporine levels following a heavy acute
      alcohol intake, and, especially, the conversion of acitretin to etretinate, in
      the presence of ethanol, with important implications in females of child-bearing
      potential. There are limited data on the contributing role of alcohol in the
      hepatotoxicity induced by some anti-psoriasis drugs and the existing information
      on this topic is still controversial. However, further investigation is needed to
      assess the relevance of interactions between alcohol consumption and drug therapy
      for psoriasis, under both pharmacological and toxicological perspectives. Long
      term prospective studies on large cohorts of patients are warranted to disclose
      the actual significance of such potential interactions in clinical practice.

PMID- 22594657
TI  - New 2-in-1 polyelectrolyte step-by-step film buildup without solution
      alternation: from PEDOT-PSS to polyelectrolyte complexes.
AB  - Although never emphasized and increasingly used in organic electronics, PEDOT-PSS
      (poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonate)) layer-by-layer (lbl)
      film construction violates the alternation of polyanion and polycation rule
      stated as a prerequisit for a step-by-step film buildup. To demonstrate that this
      alternation is not always necessary, we studied the step-by-step construction of
      films using a single solution containing polycation/polyanion complexes. We
      investigated four different systems: PEDOT-PSS, bPEI-PSS (branched poly(ethylene
      imine)-poly(sodium 4-styrene sulfonate)), PDADMA-PSS (poly(diallyl dimethyl
      ammonium)-PSS), and PAH-PSS (poly(allylamine hydrochloride)-PSS). The film
      buildup obtained by spin-coating or dipping-and-drying process was monitored by
      ellipsometry, UV-vis-NIR spectrophotometry, and quartz-crystal microbalance. The
      surface morphology of the films was characterized by atomic force microscopy in
      tapping mode. After an initial transient regime, the different films have a
      linear buildup with the number of deposition steps. It appears that, when the
      particles composed of polyanion-polycation complex and complex aggregates in
      solution are more or less liquid (case of PEDOT-PSS and bPEI-PSS), our method
      leads to smooth films (roughness on the order of 1-2 nm). On the other hand, when
      these complexes are more or less solid particles (case of PDADMA-PSS and PAH
      PSS), the resulting films are much rougher (typically 10 nm).
      Polycation/polyanion molar ratios in monomer unit of the liquid, rinsing, and
      drying steps are key parameters governing the film buildup process with an
      optimal polycation/polyanion molar ratio leading to the fastest film growth. This
      new and general lbl method, designated as 2-in-1 method, allows obtaining regular
      and controlled film buildup with a single liquid containing polyelectrolyte
      complexes and opens a new route for surface functionalization with
      polyelectrolytes.

PMID- 22594658
TI  - Can dietary fibre help provide safer food products for sufferers of gluten
      intolerance? A well-established biophysical probe may help towards providing an
      answer.
AB  - Gluten intolerance is a condition which affects an increasing percentage of the
      world's population and for which the only current treatment is a restrictive
      gluten free diet. However could the inclusion of a particular polysaccharide, or
      blends of different types, help with the provision of 'safer' foods for those
      individuals who suffer from this condition? We review the current knowledge on
      the prevalence, clinical symptoms and treatment of gluten intolerance, and the
      use and properties of the allergens responsible. We consider the potential for
      dietary fibre polysaccharides to sequester peptides that are responsible for
      activation of the disease in susceptible individuals, and consider the potential
      of co-sedimentation in the analytical ultracentrifuge as a molecular probe for
      finding interactions strong enough to be considered as useful.

PMID- 22594659
TI  - Characterization of double layer alterations induced by charged particles and
      protein-membrane interactions using contactless impedance spectroscopy.
AB  - Double layer interactions between charged particles and surfaces play a vital
      role in a variety of technical and biological systems because they determine the
      stability of, e.g., protein-membrane biointerfaces. The underlying theoretical
      principle is based on the overlap of two different double layers that induce
      surface charges to be shifted to a new equilibrium distribution, which can be
      approximated by the Poisson-Boltzmann equation. In the present work we show
      theoretical and experimental results involving double layer capacitance of
      surfaces that exhibit charge regulation behavior. Charge regulation is an
      important parameter to consider when investigating protein-membrane interactions
      because it defines surface properties between ideal constant charge and constant
      potential behavior. In this work we introduce a novel theoretical model that also
      includes charge regulation behavior and can assess changes of double layer
      disruptions at TiO(2) and supported lipid-bilayers (SLB). The selected surfaces
      represent important biointerfaces that can be found on implants or cell
      membranes. We also demonstrate that contactless impedance spectroscopy is well
      suited to measure double layer capacitance interactions using differently charged
      silica beads. The combination of a theoretical model with experimental data
      allowed us further to identify charge regulation effects during protein
      adsorption (BSA and Annexin V) events at supported lipid-bilayers (SLB) used as a
      simple cell membrane model. Finally, the first indications of changed charge
      regulation behavior during protein surface crystallization events were also
      documented.

PMID- 22594660
TI  - The sexual behaviour of adolescents in sub-Saharan Africa: patterns and trends
      from national surveys.
AB  - OBJECTIVES: To describe the sexual and reproductive behaviour of adolescents in
      sub-Saharan Africa, particularly 15- to 19-year-olds. METHODS:  Using DHS/AIS
      data (2000-2010), nine indicators of adolescent behaviour and one of adult
      attitudes towards condom education for adolescents were described for 24
      countries. Indicators were disaggregated by gender, urban/rural residency and
      educational status, and time trends were described. RESULTS: Up to 25% of 15- to
      19-year-olds reported sex before age 15; this proportion shrank over time in many
      countries. In most countries, >=5% of females reported marriage before age 15,
      and >20% had commenced childbearing. Early sexual debut and childbearing were
      more common among the least educated and/or rural females. Reporting of multiple
      sexual partnerships was more common among males than among females, but decreases
      over time were more common among males. Urban males and females, and females with
      higher education, were more likely to report multiple partnerships. Urban youth
      and those with higher education also reported more condom use. Adult support for
      condom education for 12- to 14-year-olds has increased over time to 60-65%.
      CONCLUSIONS: Many 15- to 19-year-olds are at risk of HIV/STIs and unplanned
      pregnancies because of multiple partnerships and insufficient condom and other
      contraceptive use. In many countries, trends are moving in a favourable
      direction. To better inform prevention programmes in this important area, we
      recommend routine collection of sexual and reproductive behaviour data for
      adolescents aged <15 years, expanding the data collected for 15- to 19-year-olds
      to include detailed information on sexual behaviour within partnerships, and
      disaggregating data according to sociodemographic variables.

PMID- 22594661
TI  - Strategies for the preparation and concentration of mushroom aromatic products.
AB  - Fungal aroma comprises at least seven chemical groups of volatile organic
      compounds, which are plain hydrocarbons, heterocycles, alcohols, phenols, acids
      and derivatives, carbonyls (aldehydes and ketones), and sulfur containing
      molecules. This aromatic blend provides the excellent sensory properties to
      produce and several strategies have been employed to create aromatic products
      having the aroma and taste of mushrooms and truffles. Nowadays, there are several
      procedures to obtain aroma concentrates. Among them, the simulation of mushroom
      aroma by the combination of the main substances responsible for the flavour could
      be an efficient strategy. Nevertheless, natural procedures are gaining more
      importance since the concentrate is not a synthetic product and the processes
      commonly involve the use of mushroom waste. In this field, the maceration with
      precursor molecules, such as linoleic acid, or different types of enzymes is
      commonly used in food industry. This article provides a wide view of the most
      common strategies to produce fungal aroma taking into account the main advantages
      and disadvantages they present. The article presents some promising patents on
      strategies for the preparation and concentration of mushroom aromatic products.

PMID- 22594662
TI  - Recent progress on anti-liver fibrosis candidates in patents of herbal medicinal
      products.
AB  - Liver fibrosis is a common cause of chronic failure of liver function, which is
      characterized by extracellular matrix accumulation and disruption of normal
      tissue architecture. Liver fibrosis-dependent mechanisms of hepatocarcinogenesis
      have drawn much attention. Herbal medicines are one of the strategies against
      liver fibrosis and a way to prevent hepatocellular carcinoma (HCC). Herbal
      medicines are usually used as official drugs in China, Japan and other parts of
      Asia. In this review, we retrieved and summarized current progress of anti-liver
      fibrosis candidates in USA, European and worldwide patents of herbal medicines in
      recent ten years. The pure compounds, fractions in single herbs and composite
      formulae were analyzed and discussed. The results indicated that herbal medicinal
      products can have potential on antiliver fibrosis. Further studies should focus
      on the structure modification of natural compound by computer-assisted drug
      design, quality control by acceptable worldwide guidelines, and mechanisms of
      action, drug metabolism and translational research.

PMID- 22594663
TI  - Response to "Disparities in provision of transplant information affect access to
      kidney transplantation" by Kucirka et al.

PMID- 22594664
TI  - Changes in fat mass in stroke survivors: a systematic review.
AB  - BACKGROUND: Stroke survivors have less muscle mass in their paretic limbs
      compared with nonparetic limbs, which may or may not be accompanied by changes in
      regional and/or whole body fat mass. AIM: To examine the current evidence
      regarding differences in regional fat mass between paretic and nonparetic limbs
      and changes in whole body fat mass over time in stroke survivors. METHODS: A
      systematic search of relevant databases. Studies measuring whole body or regional
      fat mass using dual-energy X-ray absorpiometry, computed tomography, or magnetic
      resonance imaging were included. RESULTS: Eleven trials were identified. Fat mass
      differences between paretic and nonparetic limbs and change in fat mass over time
      were not consistent. Meta-analyses were conducted using dual-energy X-ray
      absorpiometry-derived data from 10 trials (n = 324). There were no differences in
      fat mass between paretic and nonparetic legs (pooled mean difference 31.4 g, 95%
      confidence interval -33.9 to 96.6, P = 0.35), and slightly greater fat mass in
      the paretic arms compared with nonparetic arms (pooled mean difference 84.0 g,
      95% confidence interval 30.7 to 137.3, P = 0.002). Whole body fat mass did not
      increase significantly between one-month and six-months poststroke (pooled mean
      difference 282.3 g, 95% confidence interval -824.4 to 1389, P = 0.62), but there
      was an increase between six- and 12 months poststroke (pooled mean difference
      1935 g, 95% confidence interval 1031 to 2839, P < 0.001). CONCLUSIONS: There were
      inconsistent findings regarding changes in fat mass after stroke. Large, well
      designed studies are required to further investigate the impact of body
      composition changes on the health of stroke survivors.

PMID- 22594665
TI  - Laser shock-based platform for controllable forming of nanowires.
AB  - One-dimensional nanomaterials have attracted a great deal of research interest in
      the past few decades due to their unique mechanical, electrical, and optical
      properties. Changing the shape of nanowires (NWs) is both challenging and crucial
      to change the property and open wide functions of NWs, such as strain
      engineering, electronic transport, mechanical properties, band structure, and
      quantum properties, etc. Here we report a scalable strategy to conduct cutting,
      bending, and periodic straining of NWs by making use of laser shock pressure.
      Three-dimensional shaping of silver NWs is demonstrated, during which the Ag NWs
      exhibit very good ductility (strain-to-failure reaches 110%). Meanwhile, the high
      electrical conductivity of Ag NWs could retain well under controlled laser shock
      pressure. The microstructure observation indicates that the main deformation
      mechanism in Ag NWs under dynamic loading is formation of twinning and stacking
      fault, while dislocation motion and pile-up is less obvious. This method could be
      applied to semiconductor NWs as well.

PMID- 22594667
TI  - Short chain chlorinated paraffins in mollusks from coastal waters in the Chinese
      Bohai Sea.
AB  - As an extremely complex group of persistent organic pollutants (POPs) candidates
      in the Stockholm Convention, short chain chlorinated paraffins (SCCPs) have been
      of extensive concern in recent years. In this study, nine bivalve and two
      gastropod species were collected in 2009 to evaluate the spatial distributions
      and potential factors influencing the bioaccumulation of SCCPs in mollusks in the
      Chinese Bohai Sea. The concentrations of ? SCCPs in the mollusks were in the
      range 64.9-5510 ng/g (dry weight) with an average chlorine content of 61.1%.
      C(10) and C(11) were the predominant homologue groups of SCCPs, which accounted
      for about 29.7% and 34.9% of ? SCCPs, respectively. Six and seven chlorinated
      substituents were the main congener groups.  Mya arenaria  (Mya),  Mactra
      veneriformis  (Mac), and  Crassostrea talienwhanensis  (Oyster, Ost) had higher
      average concentrations of SCCPs than other species, implying that these bivalves
      could be used as sentinels to indicate SCCPs contamination in this coastal
      region. A significant positive linear relationship was found between SCCP
      concentrations and lipid content of the mollusks, whereas the lipid-normalized
      SCCP concentrations were negatively linear-related to the trophic levels (TL),
      which implied that SCCPs did not show biomagnification in mollusks in this
      region.

PMID- 22594668
TI  - Recollections of a genetical plant pathologist.

PMID- 22594666
TI  - Parkinson's disease and immune system: is the culprit LRRKing in the periphery?
AB  - Leucine-rich repeat kinase 2 (LRRK2) is a large multidomain kinase/GTPase that
      has been recently linked to three pathological conditions: Parkinson's disease;
      Crohn's disease; and leprosy. Although LRRK2 physiological function is poorly
      understood, a potential role in inflammatory response is suggested by its high
      expression in immune cells and tissues, its up-regulation by interferon gamma,
      and its function as negative regulator of the immune response transcription
      factor NFAT1. In this review we discuss the most recent findings regarding how
      LRRK2 could be a player in the inflammatory response and we propose a scenario
      where the detrimental effects mediated by Parkinson's disease LRRK2 mutations may
      initiate in the periphery and extend to the central nervous system as a
      consequence of increased levels of pro-inflammatory factors permeable to the
      blood brain barrier.

PMID- 22594669
TI  - Functional social support within a medical supervised outpatient treatment
      program.
AB  - BACKGROUND: This study examined functional social support (FSS) and its impact on
      treatment outcome in alcohol-dependent outpatients treated with supervised
      disulfiram. METHOD: FSS was assessed cross-sectionally in 46 severe alcohol
      dependent patients participating in a close-meshed biopsychosocial treatment
      program. The FSS was measured with the Medical Outcome Study Social Support
      Survey. RESULTS: We found significantly higher FSS levels in patients with a
      current partnership. No significant influence was found of the FSS on days until
      relapse and retention time. However, FSS was positively correlated with
      cumulative abstinence. In comparison with another patient sample, it can be shown
      that the patients of the close-meshed biopsychosocial treatment program seemed to
      perceive more FSS, presumably through the higher frequency of the outpatient
      treatment contacts. CONCLUSION: High FSS is associated with a current partnership
      and with a higher cumulative time of abstinence through close professional
      supervision. A better understanding of the underlying mechanisms of social
      relationships in alcohol-dependent patients would probably help to improve
      treatment outcome in the future.

PMID- 22594671
TI  - Commentary on Wagener et al. (2012): electronic cigarettes - the Holy Grail of
      nicotine replacement?

PMID- 22594670
TI  - Cholesterol depletion modulates detergent resistant fraction of human
      serotonin(1A) receptors.
AB  - Insolubility of membrane components in non-ionic detergents such as Triton X-100
      at low temperature is a widely used biochemical criterion to identify, isolate
      and characterize membrane domains. In this work, we monitored the detergent
      insolubility of the serotonin(1A) receptor in CHO cell membranes and its
      modulation by membrane cholesterol. The serotonin(1A) receptor is an important
      member of the G-protein coupled receptor family. It is implicated in the
      generation and modulation of various cognitive, behavioral and developmental
      functions and serves as a drug target. Our results show that a significant
      fraction (~28%) of the serotonin(1A) receptor resides in detergent-resistant
      membranes (DRMs). Interestingly, the fraction of the serotonin(1A) receptor in
      DRMs exhibits a reduction upon membrane cholesterol depletion. In addition, we
      show that contents of DRM markers such as flotillin-1, caveolin-1 and GM1 are
      altered in DRMs upon cholesterol depletion. These results assume significance
      since the function of the serotonin(1A) receptor has previously been shown to be
      affected by membrane lipids, specifically cholesterol. Our results are relevant
      in the context of membrane organization of the serotonin(1A) receptor in
      particular, and G-protein coupled receptors in general.

PMID- 22594672
TI  - Rosiglitazone, a peroxisome proliferator-activated receptor gamma stimulant,
      abrogates diabetes-evoked hypertension by rectifying abnormalities in vascular
      reactivity.
AB  - In addition to insulin sensitization, rosiglitazone exhibits favourable
      circulatory effects. In the present study, we tested the hypothesis that
      rosiglitazone protects against hypertension and vascular derangements caused by
      diabetes. Diabetes was induced by a single bolus injection of streptozotocin (50
      mg/kg, i.p.). After 2 weeks, rats were started on a treatment regimen of 5 mg/kg
      rosiglitazone daily for a period of 6 weeks. The control group consisted of rats
      treated with vehicle (distilled water) for the same period of time. After 6 weeks
      treatment, blood pressure (BP) was recorded and serum levels of glucose, advanced
      glycation end-products (AGE), triglycerides, total cholesterol and low-density
      lipoprotein-cholesterol (LDL-C) were determined. In in vitro experiments,
      concentration-response curves were constructed to phenylephrine (PE), KCl and
      acetylcholine (ACh) in thoracic aorta rings. In addition, ACh-induced nitric
      oxide (NO) generation and KCl-induced intracellular Ca accumulation were
      determined in the aorta. Compared with values in control rats, both diastolic and
      systolic BP were increased in diabetic rats. Rosiglitazone treatment of diabetic
      rats abolished the increase in diastolic BP and significantly reduced the
      increased systolic BP without affecting the development of hyperglycaemia. The
      possibility that changes in vascular reactivity and/or lipid profile contributed
      to the effects of rosiglitazone on BP in diabetic rats was investigated. In
      aortic rings from diabetic rats, contractile responses to KCl were increased,
      whereas the relaxant responses to ACh were decreased. In rings from diabetic
      rosiglitazone-treated rats, the exaggerated response to KCl and the impaired
      response to ACh were abolished. Furthermore, rosiglitazone abrogated impaired ACh
      stimulated NO generation in aortas isolated from diabetic rats. Diabetes in rats
      was accompanied by elevated levels of triglycerides, total cholesterol, LDL-C and
      AGE. Rosiglitazone treatment abrogated the increased levels of triglycerides,
      total cholesterol and LDL-C, but only partially reduced AGE levels. Collectively,
      these observations indicate that rosiglitazone abrogates diabetes-evoked
      hypertension by ameliorating detrimental changes in vascular reactivity and lipid
      profiles.

PMID- 22594673
TI  - ReGAE 9: baseline factors for success following augmented trabeculectomy with
      mitomycin C in African-Caribbean patients.
AB  - BACKGROUND: To identify the baseline factors influencing success following
      trabeculectomy with mitomycin C in a case series of African-Caribbean patients.
      DESIGN: A prospective, observational and non-comparative cohort study.
      PARTICIPANTS: Forty-seven consecutive African-Caribbean patients (47 eyes) with
      glaucoma. METHODS: Association between trabeculectomy survival and study factors
      was examined using Fisher's exact test and the Wilcoxon rank sum test at 12, 24
      and 36 months following trabeculectomy. Logistic regression was used to establish
      the combination of factors best predicting survival. MAIN OUTCOME MEASURES:
      Surgical success was based upon intraocular pressure reduction to <=21 mmHg, <=18
      mmHg and <=15 mmHg without glaucoma medication (criterion 1), or intraocular
      pressure reduction to <=21 mmHg, <=18 mmHg and <=15 mmHg with or without glaucoma
      medication (criterion 2). RESULTS: Trabeculectomy survival at 36 months was
      significantly decreased with the use of preoperative acetazolamide, pseudophakic
      status and higher preoperative intraocular pressure (P < 0.05). In pseudophakic
      eyes, there was a lower rate of success for criterion 2 when aiming for an
      intraocular pressure <=15 mmHg at 2 years post-trabeculectomy, the odds ratio
      being 12. CONCLUSIONS: Three major independent risk factors were identified that
      influenced trabeculectomy failure at 3 years in African-Caribbean ethnicity: the
      preoperative use of acetazolamide, pseudophakic status and higher preoperative
      intraocular pressure. The presence of these risk factors may guide the clinician
      to use a more aggressive antiproliferative and postoperative management regime to
      enhance survival rates in this high-risk population.

PMID- 22594674
TI  - Association of asinine herpesvirus-5 with pyogranulomatous pneumonia in a mare.

PMID- 22594675
TI  - Light-dependent maintenance of hydraulic function in mangrove branches: do xylary
      chloroplasts play a role in embolism repair?
AB  - * To clarify the role of branch photosynthesis in tree functioning, the presence
      and function of chloroplasts in branch xylem tissue were studied in a diverse
      range of mangrove species growing in Australia. * The presence of xylary
      chloroplasts was observed via chlorophyll fluorescence of transverse sections.
      Paired, attached branches were selected to study the effects of covering branches
      with aluminium foil on the gas exchange characteristics of leaves and the
      hydraulic conductivity of branches. * Xylary chloroplasts occurred in all
      species, but were differently distributed among living cell types in the xylem.
      Covering stems altered the gas exchange characteristics of leaves, such that
      water-use efficiency was greater in exposed leaves of covered than of uncovered
      branches. * Leaf-specific hydraulic conductivity of stems was lower in covered
      than in uncovered branches, implicating stem photosynthesis in the maintenance of
      hydraulic function. Given their proximity to xylem vessels, we suggest that
      xylary chloroplasts may play a role in light-dependent repair of embolized xylem
      vessels.

PMID- 22594676
TI  - The SMART-COP score performs well for pneumonia risk stratification in
      Australia's Tropical Northern Territory: a prospective cohort study.
AB  - OBJECTIVE: To prospectively compare a modified pneumonia severity scoring system,
      SMARTACOP, with other severity scores in patients presenting with pneumonia to
      the emergency department (ED) of a tertiary referral hospital in tropical
      Australia. METHODS: We conducted a prospective observational study of adult
      patients presenting with radiologically confirmed pneumonia over a 12-month
      period. The sensitivity of risk stratification scores were assessed against the
      need for intensive respiratory or vasopressor support (IRVS). RESULTS: There were
      367 ED attendances for pneumonia of whom 77.1% were admitted to hospital, 10%
      required intensive respiratory or vasopressor support and 2.8% died. Mean age was
      50.0 years, 52% were men and 59% were Indigenous. The sensitivity of a SMART-COP
      score >=3, a SMARTACOP score >=3 and a pneumonia severity index (PSI) class >=3
      for predicting IRVS was 97%, 97% and 78% respectively. CONCLUSIONS: We found no
      significant advantage of the SMARTACOP over the SMART-COP score for the
      prediction of intensive respiratory or vasopressor support, but both scores
      significantly outperformed PSI. The SMART-COP score should replace the PSI in
      tropical Australia and should be assessed in other tropical areas for pneumonia
      risk stratification in emergency departments.

PMID- 22594677
TI  - Statistics of multiscale fluctuations in macromolecular systems.
AB  - An approach is suggested for treating multiscale fluctuations in macromolecular
      systems. The emphasis is on the statistical properties of such fluctuations. The
      approach is illustrated by a macromolecular system with mesoscopic fluctuations
      between the states of atomic orbitals. Strong-orbital and weak-orbital couplings
      fluctuationally arise, being multiscale in space and time. Statistical properties
      of the system are obtained by averaging over the multiscale fluctuations. The
      existence of such multiscale fluctuations causes phase transitions between strong
      coupling and weak-coupling states. These transitions are connected with structure
      and size transformations of macromolecules. An approach for treating density and
      size multiscale fluctuations by means of classical statistical mechanics is also
      advanced.

PMID- 22594678
TI  - The effect of health education intervention on the home management of malaria
      among the caregivers of children aged under 5 years in Ogun State, Nigeria.
AB  - BACKGROUND: Malaria is currently the most important cause of death and disability
      in children aged under 5 years in Africa. A health education interventional study
      of this nature is essential in primary control of an endemic communicable disease
      such as malaria. This study was therefore designed to determine the effect of
      health education on the home management of Malaria among the caregivers of
      children under 5 years old in Ogun State, Nigeria. METHODS: The study design was
      a quasi-experimental study carried out in Ijebu North Local Government Area of
      Ogun State. A multistage random sampling technique was used in choosing the
      required samples for this study and a semi-structured questionnaire was used to
      collect relevant information. The intervention consisted of a structured
      educational program based on a course content adapted from the national malaria
      control program. A total of 400 respondents were recruited into the study, with
      200 each in both the experimental and control groups, and were followed up for a
      period of 3 months when the knowledge and uptake of insecticide treated net was
      reassessed. RESULTS: There was no statistically significant differences observed
      between the experimental and control groups in terms of sociodemographic
      characteristics such as age (P = 0.99), marital status (P = 0.48), religion (P =
      0.1), and income (P = 0.51). The majority in both the experimental (75.0%) and
      control (71.5%) groups use arthemisinin-based combination therapy as first line
      home treatment drugs pre intervention. Post health education intervention, the
      degree of change in the knowledge of referral signs and symptoms in the
      experimental group was 52.8% (P < 0.0001) while it was 0.2% in the control group
      (P = 0.93). Tepid sponging improved by 45.0%, paracetamol use by 55.3%, and the
      use of herbs and other drugs were not significantly influenced in the
      experimental (P = 0.65 and 0.99) and control group (P = 0.89 and 0.88),
      respectively. Furthermore, there was a 55.7% (P = 0.001) increase in the
      proportion of respondents using the correct dose of arthemisinin-based
      combination therapy in the home management of malaria and 23.9% (P < 0.001) in
      the proportion using it for the required time. CONCLUSIONS: The study concludes
      that there is a shift in the home management of malaria with the use of current
      and effective antimalarial drugs. It also demonstrated the effect of health
      education on the promptness of appropriate actions taken among the respondents
      for early diagnosis and treatment. Early diagnosis and appropriate treatment can
      be guaranteed if caregivers are knowledgeable on prompt actions to be taken in
      the home management of malaria.

PMID- 22594679
TI  - Treatment options for alopecia: an update, looking to the future.
AB  - INTRODUCTION: Hair loss is a very common complaint. The diagnosis is based on
      clinical, dermoscopic and pathological examination. The treatment is usually
      continuous and requires strong compliance. AREAS COVERED: This article aims to i)
      summarize current treatment options for the most common forms of hair loss; ii)
      update the literature on treatment options to emerge over the 3 years since the
      release of the first edition of this article in 2009; and iii) outline future
      strategies for treating alopecia. EXPERT OPINION: There is good evidence-based
      information for the treatment of androgenetic alopecia. There are very few good
      quality randomized studies, and no information about long-term results for most
      of the available treatments for alopecia areata and cicatricial alopecias.
      Significant research success has been achieved over the past few years through i)
      discovering the genetic profile of alopecia areata; ii) working on follicular
      neogenesis in androgenetic alopecia; and iii) discovering the PPAR-gamma pathway
      in scarring alopecia.

PMID- 22594680
TI  - A novel approach to the analysis of human growth.
AB  - OBJECTIVES: Several formulations have been proposed in order to model human
      growth from birth to maturity. They are usually based on "ad hoc" heuristic
      assumptions. In the present contribution we adopt, as an alternative, a
      completely general (interdisciplinary) approach, based on the formalism of the
      Phenomenological Universalities (PUN). METHODS: The main PUN class investigated
      to date, i.e. UN, can only account for the overall growth pattern. For a
      realistic description it is necessary to add to it one or more "spurts", as
      expected on biological grounds, due to the stimulation of growth and sex
      hormones. RESULTS: A new PUN class (UN + FM) is generated and shown to be able to
      provide excellent agreement with standard auxological datasets. The accuracy of
      the fitting and reliability of the model suggest applications both at the
      diagnostic and therapeutic level. CONCLUSIONS: The developed formalism can be
      suitably related to the biological description of bone plate growth under
      selective hormonal stimulation on the bone epiphysis; i.e., the additional
      increase of stature is the "macroscopic" response to a well defined biological
      signal.

PMID- 22594681
TI  - Printable superhydrophilic-superhydrophobic micropatterns based on supported
      lipid layers.
AB  - A new and simple method for creating superhydrophilic micropatterns on a
      superhydrophobic surface is demonstrated. The method is based on printing an
      "ink", an ethanol solution of a phospholipid, onto a porous superhydrophobic
      surface and, thus, is compatible with a variety of commonly available printing
      techniques.

PMID- 22594682
TI  - In vitro effects of the tyrosine kinase inhibitor, masitinib mesylate, on canine
      hemangiosarcoma cell lines.
AB  - This study evaluated the in vitro activity of masitinib mesylate against canine
      hemangiosarcoma (HSA) cell lines after treatment with increasing concentrations
      of masitinib mesylate (0.01-100 uM) for 24, 48 and 72 h. Results indicated that
      masitinib mesylate caused a dose- and time-dependent decrease in HSA cell
      proliferation. The 50% inhibitory concentration (IC(50) ) at 72 h for three HSA
      cell lines (DEN, Fitz and SB) was found to be 8.56, 9.41 and 10.65 uM,
      respectively. Further investigation demonstrated that masitinib mesylate induced
      apoptosis in all HSA cell lines, including activation of caspase-3/7. Measurement
      of VEGF levels in cell supernatant found a statistically significant increased
      VEGF in close proximity to the IC(50) of each cell line followed by a decline
      back towards baseline. These findings indicate that masitinib mesylate causes
      dose-dependent HSA cell death in vitro and supports future clinical trials of
      masitinib for canine HSA.

PMID- 22594683
TI  - Preparation of chiral 3-arylpyrrolidines via the enantioselective 1,4-addition of
      arylboronic acids to fumaric esters catalyzed by Rh(I)/chiral diene complexes.
AB  - A highly efficient rhodium-catalyzed protocol for the preparation of 2
      arylsuccinic esters and 3-arylpyrrolidines of high optical purity has been
      achieved. In the presence of 1 mol % of a chiral diene/Rh(I) catalyst, asymmetric
      addition of various arylboronic acids to di-tert-butyl fumarate (3c) provides the
      corresponding adducts in up to 99% yield and 94->99.5% ee. Excellent
      enantioselectivities were also observed in the regio- and enantioselective
      conjugate addition of phenylboronic acid (4a) to compound 3e.

PMID- 22594684
TI  - Recollections and reflections.

PMID- 22594685
TI  - Bile duct expression of pancreatic and duodenal homeobox 1 in perihilar
      cholangiocarcinogenesis.
AB  - AIMS: Pancreatic and duodenal homeobox 1 (Pdx1) is a transcription factor that is
      crucial in embryogenic development and differentiation of pancreas, and its
      overexpression is reportedly involved in the progression of many malignancies,
      including pancreatic carcinoma. In this study, the role of Pdx1 was examined in
      cholangiocarcinogenesis. METHODS AND RESULTS: Forty-three cases of human
      cholangiocarcinoma (CC) and 66 cases of hepatolithiasis or primary sclerosing
      cholangitis (PSC) with biliary intraepithelial neoplasia (BilIN) lesions and also
      eight fetal and 20 adult normal livers were examined immunohistochemically. Pdx1
      was constantly expressed in the nuclei of fetal bile ducts, but was virtually
      absent in the large bile ducts of adults. By contrast, Hairy and enhancer of
      split 1 (Hes1), which represses pancreatic exocrine and endocrine
      differentiation, was expressed frequently in the adult bile ducts. Pdx1 was
      expressed in 67% of invasive CCs. In large bile ducts, expression of Pdx1
      increased while that of Hes1 decreased during the progression of BilIN lesions to
      CC. Expression of Pdx1 correlated with proliferative activities in CCs. In an in
      vitro study, all three CC cell lines expressed Pdx1 mRNA and protein. CONCLUSION:
      Up-regulation of Pdx1 is a feature of cholangiocarcinogenesis associated with
      chronic cholangitis. Furthermore, expression of Pdx1 in CC is related to
      increased proliferative activity in CCs.

PMID- 22594687
TI  - The effect of an oxygenating agent on chlorhexidine-induced extrinsic tooth
      staining: a systematic review.
AB  - BACKGROUND: Although chlorhexidine digluconate (CHX) is currently the most
      effective mouthwash for reducing plaque and gingivitis, one of its side effects
      is extrinsic tooth staining. Interestingly, oxygenating agents may reduce this
      staining. OBJECTIVE: The aim of this review was to systematically search the
      literature for data concerning the inhibiting effect of an oxygenating agent (OA)
      on CHX-induced tooth staining. METHODS: MEDLINE-PubMed, Cochrane-CENTRAL, EMBASE
      and other relevant electronic databases were searched for articles that were
      published up to November 2011. Articles were included if they were randomized
      controlled trials or controlled clinical trials conducted with healthy subjects
      >= 16 years of age that compared the effects of CHX mouthrinse combined with an
      OA with the effects of CHX alone. RESULTS: An independent screening of 1183
      titles and abstracts resulted in 4 publications that met the inclusion criteria.
      The extracted data allowed meta-analyses of intermediate length studies and
      showed that combining an OA with CHX mouthrinses led to a significant reduction
      in tooth staining (mean difference: 0.27; P = 0.02) and plaque scores (mean
      difference: 0.10; P = 0.003) when compared with CHX alone. One of the included
      studies reported a side effect for one participant. The present review was
      limited by the availability of data, and the included studies were
      methodologically and clinically heterogeneous, which affected the quality and
      interpretation of the evidence. CONCLUSION: There is moderate evidence that a
      combination of CHX and an OA reduces tooth staining without interfering with
      plaque growth inhibition.

PMID- 22594686
TI  - Thioredoxin reductase 1 deficiency enhances selenite toxicity in cancer cells via
      a thioredoxin-independent mechanism.
AB  - Selenium is an essential trace element in mammals, but is toxic at high levels.
      It is best known for its cancer prevention activity, but cancer cells are more
      sensitive to selenite toxicity than normal cells. Since selenite treatment leads
      to oxidative stress, and the Trx (thioredoxin) system is a major antioxidative
      system, we examined the interplay between TR1 (Trx reductase 1) and Trx1
      deficiencies and selenite toxicity in DT cells, a malignant mouse cell line, and
      the corresponding parental NIH 3T3 cells. TR1-deficient cells were far more
      sensitive to selenite toxicity than Trx1-deficient or control cells. In contrast,
      this effect was not seen in cells treated with hydrogen peroxide, suggesting that
      the increased sensitivity of TR1 deficiency to selenite was not due to oxidative
      stress caused by this compound. Further analyses revealed that only TR1-deficient
      cells manifested strongly enhanced production and secretion of glutathione, which
      was associated with increased sensitivity of the cells to selenite. The results
      suggest a new role for TR1 in cancer that is independent of Trx reduction and
      compensated for by the glutathione system. The results also suggest that the
      enhanced selenite toxicity of cancer cells and simultaneous inhibition of TR1 can
      provide a new avenue for cancer therapy.

PMID- 22594688
TI  - Development of an influenza virus protein array using Sortagging technology.
AB  - Protein array technology is an emerging tool that enables high-throughput
      screening of protein-protein or protein-lipid interactions and identification of
      immunodominant antigens during the course of a bacterial or viral infection. In
      this work, we developed an Influenza virus protein array using the sortase
      mediated transpeptidation reaction known as "Sortagging". LPETG-tagged Influenza
      virus proteins from bacterial and eukaryotic cellular extracts were immobilized
      at their carboxyl-termini onto a preactivated amine-glass slide coated with a
      Gly3 linker. Immobilized proteins were revealed by specific antibodies, and the
      newly generated Sortag-protein chip can be used as a device for antigen and/or
      antibody screening. The specificity of the Sortase A (SrtA) reaction avoids
      purification steps in array building and allows immobilization of proteins in an
      oriented fashion. Previously, this versatile technology has been successfully
      employed for protein labeling and protein conjugation. Here, the tool is
      implemented to covalently link proteins of a viral genome onto a solid support.
      The system could readily be scaled up to proteins of larger genomes in order to
      develop protein arrays for high-throughput screening. 

PMID- 22594689
TI  - Early supported discharge after stroke in Bergen (ESD Stroke Bergen): a
      randomized controlled trial comparing rehabilitation in a day unit or in the
      patients' homes with conventional treatment.
AB  - RATIONALE: As a result of demographic changes with a presumed rapidly increasing
      number of older people during the coming decades, a strong increase in the
      incidence and prevalence of stroke should be expected. Early supported discharge
      implies that the patients are discharged to their homes as soon as feasible and
      that rehabilitative treatment is offered after the discharge, with the patients
      being home-dwelling. This has proved beneficial in previous studies. AIMS: The
      main objective of this study is to further characterize the important components
      of early supported discharge and to confirm superiority of early supported
      discharge over conventional treatment. The secondary aim will be to compare two
      different early supported discharge schemes. These early supported discharge
      schemes are composed of intensive rehabilitation treatment given by a
      multidisciplinary team in a day unit and, alternatively, the same treatment given
      in the patients' homes. DESIGN: The study is conducted as a randomized controlled
      trial with three arms: two different forms of early supported discharge and a
      control arm with conventional treatment. Patients with acute stroke admitted to
      our hospital's stroke unit and living in the Municipality of Bergen are
      considered for inclusion. A total of 350 stroke patients are expected. STUDY
      OUTCOMES: Primary outcome is modified Rankin Scale six-months after inclusion.
      Secondary outcomes include Barthel Index and National Institute of Health Stroke
      Scale at several points in time after inclusion, as well as many other schemes,
      questionnaires and physical tests. The study is registered in ClinicalTrials.gov
      registration number NCT00771771.

PMID- 22594690
TI  - A selective, orally bioavailable 1,2,4-triazolo[1,5-a]pyridine-based inhibitor of
      Janus kinase 2 for use in anticancer therapy: discovery of CEP-33779.
AB  - Members of the JAK family of nonreceptor tyrosine kinases play a critical role in
      the growth and progression of many cancers and in inflammatory diseases. JAK2 has
      emerged as a leading therapeutic target for oncology, providing a rationale for
      the development of a selective JAK2 inhibitor. A program to optimize selective
      JAK2 inhibitors to combat cancer while reducing the risk of immune suppression
      associated with JAK3 inhibition was undertaken. The structure-activity
      relationships and biological evaluation of a novel series of compounds based on a
      1,2,4-triazolo[1,5-a]pyridine scaffold are reported. Para substitution on the
      aryl at the C8 position of the core was optimum for JAK2 potency (17).
      Substitution at the C2 nitrogen position was required for cell potency (21).
      Interestingly, meta substitution of C2-NH-aryl moiety provided exceptional
      selectivity for JAK2 over JAK3 (23). These efforts led to the discovery of CEP
      33779 (29), a novel, selective, and orally bioavailable inhibitor of JAK2.

PMID- 22594691
TI  - Gender differences in experiences of ART services in South Africa: a mixed
      methods study.
AB  - OBJECTIVES: A mixed methods study exploring gender differences in patient
      profiles and experiences of ART services, along the access dimensions of
      availability, affordability and acceptability, in two rural and two urban areas
      of South Africa. METHODS: Structured exit interviews (n = 1266) combined with in
      depth interviews (n = 20) of women and men enrolled in ART care. RESULTS: Men
      attending ART services were more likely to be employed (29%vs. 20%, P = 0.001)
      and were twice as likely to be married/co-habiting as women (42%vs. 22%P =
      0.001). Men had known their HIV status for a shorter time (mean 32 vs. 36 months,
      P = 0.021) and were also less likely to disclose their status to non-family
      members (17%vs. 26%, P = 0.001). From both forms of data collection, a key
      finding was the role of female partners in providing social support and
      facilitating use of services by men. The converse was true for women who relied
      more on extended families and friends than on partners for support. Young,
      unmarried and unemployed men faced the greatest social isolation and difficulty.
      There were no major gender differences in the health system (supply side)
      dimensions of access. CONCLUSIONS: Gender differences in experiences of HIV
      services relate more to social than health system factors. However, the health
      system could be more responsive by designing services in ways that enable earlier
      and easier use by men.

PMID- 22594692
TI  - Prediction equations for fat and fat-free body mass in adolescents, based on body
      circumferences.
AB  - BACKGROUND: Fat mass (FM) and fat-free body mass (FFB) are important parameters
      for assessing nutritional status, since they are associated with higher
      prevalence of excess body fat and malnutrition worldwide. AIM: To develop
      prediction equations for fat and fat-free body mass in adolescents using body
      circumferences. SUBJECTS AND METHODS: This cross-sectional study included 218
      adolescents (10-16 years) with normal weight as defined by body mass index.
      FM(Pred) and FFB(Pred) were estimated using stepwise multiple linear regression,
      considering age and body circumferences. Response variables, FM(BIA) and FFB(BIA)
      were estimated using bioelectric impedance analysis (BIA). The accuracy of the
      prediction equations was evaluated using the coefficient of determination (R(2))
      and Akaike's Information Criterion (AIC). RESULTS: The best prediction equations
      for males were FM(Pred) = -7.114 - 0.592(age) -
      0.958(wrist)+0.191(hip)+0.295(abdomen); R(2) = 0.552; AIC = 416.04 and FFB(Pred)
      = - 52.180+1.913(age)+1.954(wrist)+1.635(forearm); R(2) = 0.869; AIC = 578.24.
      For females, the best equations were FM(Pred) = -17.580 -
      0.678(wrist)+0.221(abdomen)+0.241(hip)+0.202(proximal thigh) - 0.228(calf); R(2)
      = 0.838; AIC = 415.36 and FFB(Pred) = -31.066+0.90(age)+1.090(wrist) -
      0.139(abdomen)+0.326(hip)+0.632(calf); R(2) = 0.878; AIC = 512.48. CONCLUSION:
      The equations developed to estimate fat body mass in females and fat-free body
      mass in both genders had high adjusted coefficients of determination and are
      therefore preferable to those derived using BIA.

PMID- 22594693
TI  - Transfer kinetics of polar organic compounds over polyethersulfone membranes in
      the passive samplers POCIS and Chemcatcher.
AB  - Passive samplers for polar organic compounds often use a polyethersulfone (PES)
      membrane to retain the particulate sorbent material (e.g., in a POCIS; polar
      organic chemical integrative sampler) or to reduce the sampling rate and thus
      extend the kinetic regime (e.g., in a Chemcatcher). The transport kinetics over
      the PES membrane are evaluated here in a short-term (6 days) and a long-term (32
      days) experiment with POCIS and Chemcatchers. Passive samplers were placed in a
      channel with flowing river water that was spiked with 22 organic chemicals
      including pharmaceuticals, pesticides and biocides; with logK(ow) (logarithmic
      octanol-water partitioning coefficient) values between -2.6 and 3.8. Samplers
      were removed at intervals and membranes and sorbent material were extracted and
      analyzed with LC-MS/MS. Uptake kinetics of the compounds fell between two
      extremes: (1) charged chemicals and chemicals of low hydrophobicity did not
      accumulate in PES and rapidly transferred to the sorbent (e.g., diclofenac) and
      (2) more hydrophobic chemicals accumulated strongly in the PES and appeared in
      the sorbent after a lag-phase (e.g., diazinon and diuron). Sorption kinetics were
      modeled with a three-compartment first-order kinetic model to determine uptake
      and elimination rate constants and partitioning coefficients. Water PES
      partitioning coefficients fitted with the model correlated well with
      experimentally determined values and logK(ow). Sampling rates of Chemcatcher
      (0.02-0.10 L/d) and POCIS (0.02-0.30 L/d) showed similar patterns and correlated
      well. Thus the samplers are interchangeable in practical applications. Longer lag
      phases may pose problems when calculating time-weighted average aqueous
      concentrations for short passive sampling windows and for a correct integrative
      sampling of fluctuating concentrations.

PMID- 22594694
TI  - Which patients are more likely to benefit from renal transplantation?
AB  - BACKGROUND: We evaluated whether the advantages conferred by renal
      transplantation encompass all individuals or whether they favor more specific
      groups of patients. METHODS: One thousand and fifty-eight patients on the
      transplant waiting list and 270 receiving renal transplant were studied. End
      points were the composite incidence of CV events and death. Patients were
      followed up from date of placement on the list until transplantation, CV event,
      or death (dialysis patients), or from the date of transplantation, CV event,
      return to dialysis, or death (transplant patients). RESULTS: Younger patients
      with no comorbidities had a lower incidence of CV events and death independently
      of the treatment modality (log-rank=0.0001). Renal transplantation was associated
      with better prognosis only in high-risk patients (p=0.003). CONCLUSIONS: Age and
      comorbidities influenced the prevalence of CV complications and death
      independently of the treatment modality. A positive effect of renal
      transplantation was documented only in high-risk patients. These findings suggest
      that age and comorbidities should be considered indication for early
      transplantation even considering that, as a group, such patients have a shorter
      survival compared with low-risk individuals.

PMID- 22594695
TI  - Keratometry obtained by corneal mapping versus the IOLMaster in the prediction of
      postoperative refraction in routine cataract surgery.
AB  - BACKGROUND: To establish whether simulated keratometry values obtained by corneal
      mapping (videokeratography) would provide a superior refractive outcome to those
      obtained by Zeiss IOLMaster (partial coherence interferometry) in routine
      cataract surgery. DESIGN: Prospective, non-randomized, single-surgeon study set
      at the The Royal United Hospital, Bath, UK, District General Hospital.
      PARTICIPANTS: Thirty-three patients undergoing routine cataract surgery in the
      absence of significant ocular comorbidity. METHODS: Conventional biometry was
      recorded using the Zeiss IOLMaster. Postoperative refraction was calculated using
      the SRK/T formula and the most appropriate power of lens implanted. Preoperative
      keratometry values were also obtained using Humphrey Instruments Atlas Version A6
      corneal mapping. MAIN OUTCOME MEASURES: Achieved refraction was compared with
      predicted refraction for the two methods of keratometry after the A-constants
      were optimized to obtain a mean arithmetic error of zero dioptres for each
      device. RESULTS: The mean absolute prediction error was 0.39 dioptres (standard
      deviation 0.29) for IOLMaster and 0.48 dioptres (standard deviation 0.31) for
      corneal mapping (P = 0.0015). Keratometry readings between the devices were
      highly correlated by Spearman correlation (0.97). The Bland-Altman plot
      demonstrated close agreement between keratometers, with a bias of 0.0079 dioptres
      and 95% limits of agreement of -0.48-0.49 dioptres. CONCLUSIONS: The IOLMaster
      was superior to Humphrey Atlas A6 corneal mapping in the prediction of
      postoperative refraction. This difference could not have been predicted from the
      keratometry readings alone. When comparing biometry devices, close agreement
      between readings should not be considered a substitute for actual postoperative
      refraction data.

PMID- 22594696
TI  - Recent Alzheimer's disease research highlights.

PMID- 22594698
TI  - Effect of age and vaccination on extent and spread of Chlamydia pneumoniae
      infection in C57BL/6 mice.
AB  - BACKGROUND: Chlamydia pneumoniae is an obligate intracellular respiratory
      pathogen for humans. Infection by C. pneumoniae may be linked etiologically to
      extra-respiratory diseases of aging, especially atherosclerosis. We have
      previously shown that age promotes C. pneumoniae respiratory infection and extra
      respiratory spread in BALB/c mice. FINDINGS: Aged C57BL/6 mice had a greater
      propensity to develop chronic and/or progressive respiratory infections following
      experimental intranasal infection by Chlamydia pneumoniae when compared to young
      counterparts. A heptavalent CTL epitope minigene (CpnCTL7) vaccine conferred
      equal protection in the lungs of both aged and young mice. This vaccine was
      partially effective in protecting against C. pneumoniae spread to the
      cardiovascular system of young mice, but failed to provide cardiovascular
      protection in aged animals. CONCLUSIONS: Our findings suggest that vaccine
      strategies that target the generation of a C. pneumoniae-specific CTL response
      can protect the respiratory system of both young and aged animals, but may not be
      adequate to prevent dissemination of C. pneumoniae to the cardiovascular system
      or control replication in those tissues in aged animals.

PMID- 22594697
TI  - Exposure to political conflict and violence and posttraumatic stress in Middle
      East youth: protective factors.
AB  - We examine the role of family- and individual-level protective factors in the
      relation between exposure to ethnic-political conflict and violence and
      posttraumatic stress among Israeli and Palestinian youth. Specifically, we
      examine whether parental mental health (lack of depression), positive parenting,
      children's self-esteem, and academic achievement moderate the relation between
      exposure to ethnic-political conflict/violence and subsequent posttraumatic
      stress (PTS) symptoms. We collected three waves of data from 901 Israeli and 600
      Palestinian youths (three age cohorts: 8, 11, and 14 years old; approximately
      half of each gender) and their parents at 1-year intervals. Greater cumulative
      exposure to ethnic-political conflict/violence across the first 2 waves of the
      study predicted higher subsequent PTS symptoms even when we controlled for the
      child's initial level of PTS symptoms. This relation was significantly moderated
      by a youth's self-esteem and by the positive parenting received by the youth. In
      particular, the longitudinal relation between exposure to violence and subsequent
      PTS symptoms was significant for low self-esteem youth and for youth receiving
      little positive parenting but was non-significant for children with high levels
      of these protective resources. Our findings show that youth most vulnerable to
      PTS symptoms as a result of exposure to ethnic-political violence are those with
      lower levels of self-esteem and who experience low levels of positive parenting.
      Interventions for war-exposed youth should test whether boosting self-esteem and
      positive parenting might reduce subsequent levels of PTS symptoms.

PMID- 22594699
TI  - Ephedrine accelerates psychomotor recovery from anesthesia in macaque monkeys.
AB  - BACKGROUND: Ephedrine is used in treatment of hypotension during anesthesia. We
      investigated its effects on the psychomotor recovery and its potential adverse
      reactions on cardiorespiratory functions in rhesus monkeys. METHODS: The monkeys
      received 50 MUg/kg medetomidine, 2.0 mg/kg S-ketamine with 150 IU hyaluronidase
      i.m. Pulse rate, blood pressure and saturation of haemoglobin were monitored for
      20 minutes. Thereafter, 1 mg/kg of ephedrine or a placebo was administered i.m.
      and behavioural changes, pulse rate, blood pressure and saturation of haemoglobin
      were monitored every 5 minutes. RESULTS: Ephedrine shortened recovery from
      anaesthesia from 80.4 +/- 25.8 to 14.83 +/- 13.70 minutes. Ephedrine also
      increased oxygen saturation of haemoglobin and systolic blood pressure and caused
      significant decrease in pulse rate 5 minutes after its administration.
      CONCLUSIONS: Ephedrine can be successfully used to accelerate psychomotor
      recovery after the use of common anesthetic protocols combining dissociative
      anesthetic agent and alpha 2-adrenoceptor agonist in primates.

PMID- 22594700
TI  - Nanoscale molecular traps and dams for ultrafast protein enrichment in high
      conductivity buffers.
AB  - We report a new approach, molecular dam, to enhance mass transport for protein
      enrichment in nanofluidic channels by nanoscale electrodeless dielectrophoresis
      under physiological buffer conditions. Dielectric nanoconstrictions down to 30 nm
      embedded in nanofluidic devices serve as field-focusing lenses capable of
      magnifying the applied field to 10(5)-fold when combined with a micro- to
      nanofluidic step interface. With this strong field and the associated field
      gradient at the nanoconstrictions, proteins are enriched by the molecular damming
      effect faster than the trapping effect, to >10(5)-fold in 20 s, orders of
      magnitude faster than most reported methods. Our study opens further
      possibilities of using nanoscale molecular dams in miniaturized sensing platforms
      for rapid and sensitive protein analysis and biomarker discovery, with potential
      applications in precipitation studies and protein crystallization and possible
      extensions to small-molecules enrichment or screening.

PMID- 22594701
TI  - Expanding the horizons of lipidomics. Towards fluxolipidomics.
AB  - This short review takes into consideration the status of lipidomics as issued
      from almost a decade of development. Because of the huge number of molecular
      species analyzed, there is a trend in subdividing lipidomics according to
      subdomains, in particular relating to the function of molecules. It is also
      pointed out that lipid imaging without the use of exogenous probes will help
      making relationships between molecular structures and the topography of lipid
      assemblies, especially in cellular compartments. Finally, a fluxomics approach is
      proposed for lipid molecular species, both in terms of compartments and
      biochemical metabolism. The example of fluxolipidomics of essential fatty acids
      toward their enzyme-dependent oxygenated metabolites and further toward their
      degradation products is developed.

PMID- 22594702
TI  - A perspective on plant pathology.

PMID- 22594703
TI  - Cervical medial branch radiofrequency neurotomy.

PMID- 22594705
TI  - Translating procedural spine science into cross-cultural clinical practice:
      methodological questions and answers.

PMID- 22594706
TI  - A cost-effectiveness analysis of the effect of pregabalin versus usual care in
      the treatment of refractory neuropathic pain in routine medical practice in
      Spain.
AB  - OBJECTIVE: The objective of this study was to estimate the cost-effectiveness of
      pregabalin vs usual care (UC) in outpatients with refractory neuropathic pain
      (NeP), treated according to routine medical practice in primary care settings in
      Spain. METHODS: Patients were extracted from a 12-week noninterventional
      prospective study conducted to ascertain the costs of NeP. Pairs of pregabalin
      naive patients receiving UC or pregabalin, matched by age, gender, pain
      intensity, and refractory to previous treatment, were selected in a 1:1 ratio.
      Refractory was considered a patient with actual pain (scoring >40 in a 100 mm in
      a pain visual analog scale) after receiving a course of a standard analgesic, at
      its recommended doses. Perspectives of the Spanish National Healthcare System and
      society were included in the analysis. Effectiveness was expressed as quality
      adjusted life-year (QALY) gain. Results of the cost-effectiveness analysis were
      expressed as an incremental cost per QALY (ICER) gained. Probabilistic
      sensitivity analysis using bootstrapping techniques was also carried out.
      RESULTS: A total of 160 pairs were extracted. Compared with UC, pregabalin was
      associated with significantly higher QALY gain; 0.0374 +/- 0.0367 vs 0.0224 +/-
      0.0313 (P < 0.001). Despite drug acquisition costs being higher for pregabalin
      (?251 +/- 125 vs ?104 +/- 121; P < 0.001), total and health care costs incurred
      for pregabalin were similar in both groups; ?1,335 +/- 1,302 vs ?1,387 +/- 1,489
      (P = 0.587) and ?529 +/- 438 vs ?560 +/- 672 (P = 0.628), respectively, yielding
      a dominant ICER for both total and health care costs in the base case scenario;
      95% confidence intervals, respectively, dominant to ?17,268, and dominant to
      ?6,508. Sensitivity analysis confirmed results of the basecase scenario.
      CONCLUSION: This study showed that pregabalin may be cost-effective in the
      treatment of refractory NeP patients when compared with UC in routine medical
      practice in Spain.

PMID- 22594708
TI  - Atomic detail brownian dynamics simulations of concentrated protein solutions
      with a mean field treatment of hydrodynamic interactions.
AB  - High macromolecular concentrations are a distinguishing feature of living
      organisms. Understanding how the high concentration of solutes affects the
      dynamic properties of biological macromolecules is fundamental for the
      comprehension of biological processes in living systems. In this paper, we
      describe the implementation of mean field models of translational and rotational
      hydrodynamic interactions into an atomically detailed many-protein brownian
      dynamics simulation method. Concentrated solutions (30-40% volume fraction) of
      myoglobin, hemoglobin A, and sickle cell hemoglobin S were simulated, and static
      structure factors, oligomer formation, and translational and rotational self
      diffusion coefficients were computed. Good agreement of computed properties with
      available experimental data was obtained. The results show the importance of both
      solvent mediated interactions and weak protein-protein interactions for
      accurately describing the dynamics and the association properties of concentrated
      protein solutions. Specifically, they show a qualitative difference in the
      translational and rotational dynamics of the systems studied. Although the
      translational diffusion coefficient is controlled by macromolecular shape and
      hydrodynamic interactions, the rotational diffusion coefficient is affected by
      macromolecular shape, direct intermolecular interactions, and both translational
      and rotational hydrodynamic interactions.

PMID- 22594709
TI  - A 'miracle cure' misunderstood.

PMID- 22594710
TI  - Gold nanoparticle-paper as a three-dimensional surface enhanced Raman scattering
      substrate.
AB  - This work investigates the effect of gold nanoparticle (AuNP) addition to paper
      substrate and examines the ability of these composite materials to amplify the
      surface enhanced Raman scattering (SERS) signal of a dye adsorbed. Paper has a
      three-dimensional (3D), porous, and heterogeneous morphology. The manner in which
      paper adsorbs the nanoparticles is crucial to its SERS properties, particularly
      with regards to aggregation. In this work, we sought to maintain the same degree
      of aggregation, while changing the concentration of nanoparticles deposited on
      paper. We achieved this by dipping paper into AuNP solutions of different, known
      concentration and found that the initial packing density of AuNPs in solutions
      was retained on paper with the same degree of aggregation. The surface coverage
      of AuNPs on paper was found to scale linearly to their concentration profile in
      solutions. The SERS performances of the AuNP-treated papers were evaluated with 4
      aminothiophenol (4-ATP) as the Raman molecule, and their SERS intensities
      increased linearly with the AuNPs' concentration. Compared to AuNP-treated
      silicon, the Raman enhancement factor (EF) from paper was relatively higher due
      to a more uniform and greater degree of adsorption of AuNPs. The effect of the
      spatial distribution of AuNPs in their substrates on SERS activity was also
      investigated. In this experiment, the number of AuNPs was kept constant (a 1 MUL
      droplet of AuNPs was deposited on all substrates), and the distribution profile
      of AuNPs was controlled by the nature of the substrate: paper, silicon, and
      hydrophobized paper. The AuNP droplet on paper showed the most reproducible and
      sensitive SERS signal. This highlighted the role of the z-distribution (through
      film) of AuNPs within the bulk of the paper, producing a 3D multilayer structure
      to allow inter- and intralayer plasmon coupling, and hence amplifying the SERS
      signal. The SERS performance of nanoparticle-functionalized paper can thus be
      optimized by controlling the 3D distribution of the metallic nanoparticles, and
      such control is critical if these systems are to be implemented as a low-cost and
      highly sensitive bioassay platform.

PMID- 22594711
TI  - Total synthesis of (-)-teucvidin.
AB  - A concise enantioselective synthesis of (-)-teucvidin has been achieved. Our
      synthetic strategy involved the diastereoselective Michael/Conia-ene cascade
      cyclization reaction for rapid establishment of the cis-decalin skeleton with
      three new stereogenic centers in one pot (72%, single diastereomer), the
      epoxidation/dealkoxycarbonylation protocol for construction of the fused furanone
      moiety, and the O-allylation/Claisen rearrangement protocol for construction of
      the all-carbon quaternary center at C9 of the clerodane skeleton.

PMID- 22594712
TI  - A novel HLA-E allele, E*01:03:05, identified in two Brazilian individuals.
AB  - Here, we report a novel non-classical class I HLA-E allele found in the Brazilian
      population.

PMID- 22594713
TI  - Hospital-based surveillance for Lassa fever in Edo State, Nigeria, 2005-2008.
AB  - OBJECTIVES: To estimate the burden of Lassa fever in northern and central Edo, a
      state in south Nigeria where Lassa fever has been reported. METHODS: Blood
      samples were obtained from 60 patients hospitalised at the Irrua Specialist
      Teaching Hospital (ISTH), Irrua, with a clinical suspicion of Lassa fever and
      from 451 febrile outpatients seen at the ISTH and hospitals in Ekpoma, Iruekpen,
      Uromi, Auchi and Igarra. All samples were tested retrospectively by Lassa virus
      specific RT-PCR. Outpatients were additionally screened for Lassa virus-specific
      antibodies by indirect immunofluorescent antibody assay. RESULTS: Lassa virus was
      detected in 25 of 60 (42%) patients with a clinical suspicion of Lassa fever. The
      disease affected persons of all age groups and with various occupations,
      including healthcare workers. The clinical picture was dominated by
      gastrointestinal symptoms. The case fatality rate was 29%. Lassa virus was
      detected in 2 of 451 (0.44%) febrile outpatients, and 8 (1.8%) were positive for
      Lassa virus-specific IgG. CONCLUSIONS: Lassa fever contributes to hospital
      mortality in Edo State. The low prevalence of the disease among outpatients and
      the low seroprevalence may indicate that the population-level incidence is not
      high. Surveillance for Lassa fever should focus on the hospitalised patient.

PMID- 22594714
TI  - Clinical analysis of emergency liver transplantation: the role of living donor
      liver transplantation.
AB  - The current liver allocation system requires reevaluation because of the
      advancements in peri-transplantation care and surgical techniques. And, the role
      of living donor liver transplantation (LDLT) in an emergency has not been
      determined yet. Retrospective review of all patients undergoing emergency liver
      transplantation (LT) from January 2000 to June 2010 was conducted, and clinical
      data were analyzed. Of the total 505 LTs, 69 patients (13.7%) underwent an
      emergency LT. Of these, 54 patients (78.3%) underwent LDLT using a right liver,
      and 15 patients (21.7%) underwent deceased donor liver transplantation (DDLT).
      The overall hospital mortality was 21.7% (15/69). The leading cause of death
      after transplantation was sepsis (60.0%). Multivariate analysis demonstrated that
      a model for end-stage liver disease (MELD)>33 [hazard ratio (HR), 16.6; 95%
      confidence interval (CI), 1.443-191.632; p=0.024] and existence of pre
      transplantation intubation (HR, 18.2; 95% CI, 1.463-225.483; p=0.024) were
      independent factors associated with poor survival after emergency LT. LDLT group
      and DDLT group showed no difference in hospital mortality (p=0.854) and graft
      survival (p=0.861). Thus, MELD score and respiratory insufficiency could be
      parameters predicting post-transplant survival. And, LDLT using the right liver
      could be an appropriate alternative to DDLT in an emergency.

PMID- 22594717
TI  - Inscriptive restorations.

PMID- 22594718
TI  - Indigenous health and climate change.
AB  - Indigenous populations have been identified as vulnerable to climate change. This
      framing, however, is detached from the diverse geographies of how people
      experience, understand, and respond to climate-related health outcomes, and
      overlooks nonclimatic determinants. I reviewed research on indigenous health and
      climate change to capture place-based dimensions of vulnerability and broader
      determining factors. Studies focused primarily on Australia and the Arctic, and
      indicated significant adaptive capacity, with active responses to climate-related
      health risks. However, nonclimatic stresses including poverty, land
      dispossession, globalization, and associated sociocultural transitions challenge
      this adaptability. Addressing geographic gaps in existing studies alongside
      greater focus on indigenous conceptualizations on and approaches to health,
      examination of global-local interactions shaping local vulnerability, enhanced
      surveillance, and an evaluation of policy support opportunities are key foci for
      future research.

PMID- 22594719
TI  - The problem with the phrase women and minorities: intersectionality-an important
      theoretical framework for public health.
AB  - Intersectionality is a theoretical framework that posits that multiple social
      categories (e.g., race, ethnicity, gender, sexual orientation, socioeconomic
      status) intersect at the micro level of individual experience to reflect multiple
      interlocking systems of privilege and oppression at the macro, social-structural
      level (e.g., racism, sexism, heterosexism). Public health's commitment to social
      justice makes it a natural fit with intersectionality's focus on multiple
      historically oppressed populations. Yet despite a plethora of research focused on
      these populations, public health studies that reflect intersectionality in their
      theoretical frameworks, designs, analyses, or interpretations are rare.
      Accordingly, I describe the history and central tenets of intersectionality,
      address some theoretical and methodological challenges, and highlight the
      benefits of intersectionality for public health theory, research, and policy.

PMID- 22594720
TI  - The economic gains of achieving reduced alcohol consumption targets for
      Australia.
AB  - OBJECTIVES: To inform prevention policy, we estimated the economic benefits to
      health, production, and leisure in the 2008 Australian population of a realistic
      target reduction in per capita annual adult alcohol consumption. METHODS: We
      chose a target of 6.4 liters annually per capita on average. We modeled lifetime
      health benefits as fewer incident cases of alcohol-related disease, deaths, and
      disability adjusted life years. We estimated production gains with surveyed
      participation and absenteeism rates. We valued gains with friction cost and human
      capital methods. We estimated and valued household production and leisure gains
      from time-use surveys. RESULTS: A reduction of 3.4 liters of alcohol consumed
      annually per capita would result in one third fewer incident cases of disease
      (98000), deaths (380), working days lost (5 million), days of home-based
      production lost (54000), and a A$789-million health sector cost reduction.
      Workforce production had a A$427 million gain when we used the friction cost
      method. By contrast, we estimated a loss of 28000 leisure days and 1000
      additional early retirements. CONCLUSIONS: Economic savings and health benefits
      from reduced alcohol consumption may be substantial-particularly in the health
      sector with reduced alcohol-related disease and injury.

PMID- 22594721
TI  - Adolescent substance use and other illegal behaviors and racial disparities in
      criminal justice system involvement: findings from a US national survey.
AB  - We used data from a national survey to examine arrest rate disparities between
      African American and White adolescents (aged 12-17 years; n=6725) in relation to
      drug-related and other illegal behaviors. African American adolescents were less
      likely than Whites to have engaged in drug use or drug selling, but were more
      likely to have been arrested. Racial disparities in adolescent arrest appear to
      result from differential treatment of minority youths and to have long-term
      negative effects on the lives of affected African American youths.

PMID- 22594722
TI  - Implementation of workplace-based smoking cessation support activities and
      smoking cessation among employees: the Finnish Public Sector Study.
AB  - OBJECTIVES: We investigated the relationship between implementation of workplace
      smoking cessation support activities and employee smoking cessation. METHODS: In
      2 cohort studies, participants were 6179 Finnish public-sector employees who self
      reported as smokers at baseline in 2004 (study 1) or 2008 (study 2) and responded
      to follow-up surveys in 2008 (study 1; n=3298; response rate = 71%) or 2010
      (study 2; n=2881; response rate=83%). Supervisors' reports were used to assess
      workplace smoking cessation support activities. We conducted multilevel logistic
      regression analyses to examine changes in smoking status. RESULTS: After
      adjustment for sociodemographic characteristics, number of cigarettes smoked per
      day, work unit size, shift work, type of job contract, health status, and health
      behaviors, baseline smokers whose supervisors reported that the employing agency
      had offered pharmacological treatments or financial incentives were more likely
      than those in workplaces that did not offer such support to have quit smoking. In
      general, associations were stronger among moderate or heavy smokers (>= 10
      cigarettes/day) than among light smokers (<10 cigarettes/day). CONCLUSIONS:
      Cessation activities offered by employers may encourage smokers, particularly
      moderate or heavy smokers, to quit smoking.

PMID- 22594723
TI  - The case for the World Health Organization's Commission on the Social
      Determinants of Health to address sexual orientation.
AB  - The World Health Organization's (WHO's) social determinants of health discussion
      underscores the need for health equity and social justice. Yet sexual orientation
      was not addressed within the WHO Commission on the Social Determinants of Health
      final report Closing the Gap in a Generation.  This omission of sexual
      orientation as a social determinant of health stands in stark contrast with a
      body of evidence that demonstrates that sexual minorities are disproportionately
      affected by health problems associated with stigma and discrimination, such as
      mental health disorders.  I propose strategies to integrate sexual orientation
      into the WHO's social determinants of health dialogue. Recognizing sexual
      orientation  as a social determinant of health is an important first step toward
      health equity for sexual minorities.

PMID- 22594725
TI  - Implementation of wireless terminals at farmers' markets: impact on SNAP
      redemption and overall sales.
AB  - Although farmers' markets offer healthy foods for purchase, many lack the
      equipment necessary to process convenient, card-based transactions. We assessed
      the impact of providing wireless terminals to 5 markets on overall sales and
      redemption of Supplemental Nutrition Assistance Program (SNAP) benefits. Sales
      increased significantly at 4 of the 5 markets after implementation of the
      terminals, and overall sales increased above and beyond SNAP redemption alone.
      Implementation of wireless terminals may be important for improving the financial
      stability and accessibility of farmers' markets.

PMID- 22594726
TI  - Public health policy is political.

PMID- 22594728
TI  - Menthol brand switching among adolescents and young adults in the National Youth
      Smoking Cessation Survey.
AB  - This study examines patterns of menthol and nonmenthol cigarette use from 2003 to
      2005 in a cohort of smokers, aged 16 to 24 years in the National Youth Smoking
      Cessation Survey. At follow-up, 15.0% of baseline menthol smokers had switched to
      nonmentholated cigarettes; by contrast, 6.9% of baseline nonmenthol smokers had
      switched to mentholated cigarettes. Differences in switching patterns were
      evident by gender, race/ethnicity, parental education, and smoking frequency.
      These data support previous evidence that young smokers start with mentholated
      cigarettes and progress to nonmentholated cigarettes.

PMID- 22594727
TI  - Social patterning of cumulative biological risk by education and income among
      African Americans.
AB  - OBJECTIVES: We examined the social patterning of cumulative dysregulation of
      multiple systems, or allostatic load, among African Americans adults. METHODS: We
      examined the cross-sectional associations of socioeconomic status (SES) with
      summary indices of allostatic load and neuroendocrine, metabolic, autonomic, and
      immune function components in 4048 Jackson Heart Study participants. RESULTS:
      Lower education and income were associated with higher allostatic load scores in
      African American adults. Patterns were most consistent for the metabolic and
      immune dimensions, less consistent for the autonomic dimension, and absent for
      the neuroendocrine dimension among African American women. Associations of SES
      with the global allostatic load score and the metabolic and immune domains
      persisted after adjustment for behavioral factors and were stronger for income
      than for education. There was some evidence that the neuroendocrine dimension was
      inversely associated with SES after behavioral adjustment in men, but the immune
      and autonomic components did not show clear dose-response trends, and we observed
      no associations for the metabolic component. CONCLUSIONS: Findings support our
      hypothesis that allostatic load is socially patterned in African American women,
      but this pattern is less consistent in African American men.

PMID- 22594729
TI  - Global health-a circumpolar perspective.
AB  - Global health should encompass circumpolar health if it is to transcend the
      traditional approach of the "rich North" assisting the "poor South." Although the
      eight Arctic states are among the world's most highly developed countries,
      considerable health disparities exist among regions across the Arctic, as well as
      between northern and southern regions and between indigenous and nonindigenous
      populations within some of these states.  While sharing commonalities such as a
      sparse population, geographical remoteness, harsh physical environment, and
      underdeveloped human resources, circumpolar regions in the northern hemisphere
      have developed different health systems, strategies, and practices, some of which
      are relevant to middle and lower income countries.  As the Arctic gains
      prominence as a sentinel of global issues such as climate change, the health of
      circumpolar populations should be part of the global health discourse and policy
      development.

PMID- 22594730
TI  - Lessons learned from a community-academic initiative: the development of a core
      competency-based training for community-academic initiative community health
      workers.
AB  - OBJECTIVES: Despite the importance of community health workers (CHWs) in
      strategies to reduce health disparities and the call to enhance their roles in
      research, little information exists on how to prepare CHWs involved in community
      academic initiatives (CAIs). Therefore, the New York University Prevention
      Research Center piloted a CAI-CHW training program. METHODS: We applied a core
      competency framework to an existing CHW curriculum and bolstered the curriculum
      to include research-specific sessions. We employed diverse training methods,
      guided by adult learning principles and popular education philosophy. Evaluation
      instruments assessed changes related to confidence, intention to use learned
      skills, usefulness of sessions, and satisfaction with the training. RESULTS:
      Results demonstrated that a core competency-based training can successfully
      affect CHWs' perceived confidence and intentions to apply learned content, and
      can provide a larger social justice context of their role and work. CONCLUSIONS:
      This program demonstrates that a core competency-based framework coupled with CAI
      research-specific skill sessions (1) provides skills that CAI-CHWs intend to use,
      (2) builds confidence, and (3) provides participants with a more contextualized
      view of client needs and CHW roles.

PMID- 22594733
TI  - Racial residential segregation and rates of gonorrhea in the United States, 2003
      2007.
AB  - OBJECTIVES: In the United States, Black persons are disproportionately affected
      by sexually transmitted infections (STIs), including gonorrhea. Individual
      behaviors do not fully explain these racial disparities. We explored the
      association of racial residential segregation with gonorrhea rates among Black
      persons and hypothesized that specific dimensions of segregation would be
      associated with gonorrhea rates. METHODS: We used 2003 to 2007 national STI
      surveillance data and 2000 US Census Bureau data to examine associations of 5
      dimensions of racial residential segregation and a composite measure of
      hypersegregation with gonorrhea rates among Black persons in 257 metropolitan
      statistical areas, overall and by sex and age. We calculated adjusted rate ratios
      with generalized estimating equations. RESULTS: Isolation and unevenness were
      significantly associated with gonorrhea rates. Centralization was marginally
      associated with gonorrhea. Isolation was more strongly associated with gonorrhea
      among the younger age groups. Concentration, clustering, and hypersegregation
      were not associated with gonorrhea. CONCLUSIONS: Certain dimensions of
      segregation are important in understanding STI risk among US Black persons.
      Interventions to reduce sexual risk may need to account for racial residential
      segregation to maximize effectiveness and reduce existent racial disparities.

PMID- 22594734
TI  - Utilizing screening, brief intervention, and referral to treatment: teaching
      assessment of substance abuse.
AB  - Although social workers regularly encounter clients with substance use problems,
      social work education rarely addresses addictions with any depth. This pilot
      study explored the use of screening, brief intervention, and referral to
      treatment (SBIRT) with 74 social work students. Students completed SBIRT training
      with pre- and post-questionnaires that assessed attitudes, knowledge, and skills
      concerning substance misuse. Statistically significant differences were
      demonstrated with students reporting more confidence in their ability to
      successfully assess for alcohol misuse and subsequently intervene.

PMID- 22594735
TI  - Slums and malnourishment: evidence from women in India.
AB  - OBJECTIVES: We examined the association between slum residence and nutritional
      status in women in India by using competing classifications of slum type.
      METHODS: We used nationally representative data from the 2005-2006 National
      Family Health Survey (NFHS-3) to create our citywide analysis sample. The data
      provided us with individual, household, and community information. We used the
      body mass index data to identify nutritional status, whereas the residential
      status variable provided slum details. We used a multinomial regression framework
      to model the 3 nutrition states-undernutrition, normal, and overnutrition.
      RESULTS: After we controlled for a range of attributes, we found that living in a
      census slum did not affect nutritional status. By contrast, living in NFHS slums
      decreased the odds of being overweight by 14% (95% confidence interval [CI]
      =0.79, 0.95) and increased the odds of being underweight by 10% (95% CI=1.00,
      1.22). CONCLUSIONS: The association between slum residence and nutritional
      outcomes is nuanced and depends on how one defines a slum. This suggests that
      interventions targeted at slums should look beyond official definitions and
      include current living conditions to effectively reach the most vulnerable.

PMID- 22594736
TI  - A call for further research on the impact of state-level immigration policies on
      public health.
AB  - Arizona's Support Our Law Enforcement and Safe Neighborhoods Act, signed into law
      in April 2010, is already adversely affecting public health in the state.  Our
      findings from a study on childhood obesity in Flagstaff suggest that the law
      changed health-seeking behaviors of residents of a predominantly Latino
      neighborhood by increasing fear, limiting residents' mobility, and diminishing
      trust of officials. These changes could exacerbate barriers to healthy living,
      limit access to care, and affect the overall safety of the neighborhood. 
      Documentation of the on-the-ground impact of Arizona's law and similar state
      level immigration policies is urgently needed. To inform effective policymaking,
      such research must be community engaged and include safety measures beyond the
      usual protocols.

PMID- 22594737
TI  - Comments From the South Side of Chicago on New Haven's Inspiring Initiative.

PMID- 22594738
TI  - Screening for unidentified increased systemic disease risk in a dental setting.

PMID- 22594739
TI  - Changes in smoking prevalence in 8 countries of the former Soviet Union between
      2001 and 2010.
AB  - OBJECTIVES: We sought to present new data on smoking prevalence in 8 countries,
      analyze prevalence changes between 2001 and 2010, and examine trend variance by
      age, location, education level, and household economic status. METHODS: We
      conducted cross-sectional household surveys in 2010 in Armenia, Belarus, Georgia,
      Kazakhstan, Kyrgyzstan, Moldova, Russia, and Ukraine. We compared smoking
      prevalence with a related 2001 study for the different countries and population
      subgroups, and also calculated the adjusted prevalence rate ratios of smoking.
      RESULTS: All-age 2010 smoking prevalence among men ranged from 39% (Moldova) to
      59% (Armenia), and among women from 2% (Armenia) to 16% (Russia). There was a
      significantly lower smoking prevalence among men in 2010 compared with 2001 in
      Belarus, Kazakhstan, Kyrgyzstan, and Russia, but not for women in any country.
      For all countries combined, there was a significantly lower smoking prevalence in
      2010 than in 2001 for men aged 18 to 39 years and men with a good or average
      economic situation. CONCLUSIONS: Smoking prevalence appears to have stabilized
      and may be declining in younger groups, but remains extremely high among men,
      especially those in lower socioeconomic groups.

PMID- 22594740
TI  - High food insecurity and its correlates among families living on a rural American
      Indian Reservation.
AB  - OBJECTIVES: We sought to better understand the prevalence and consequences of
      food insecurity among American Indian families with young children. METHODS:
      Parents or caregivers of kindergarten-age children enrolled in the Bright Start
      study (dyad n=432) living on the Pine Ridge Reservation in South Dakota completed
      a questionnaire on their child's dietary intake, the home food environment, and
      food security. We assessed food security with a standard 6-item scale and
      examined associations of food insecurity with family sociodemographic
      characteristics, parents' and children's weight, children's dietary patterns, and
      the home food environment. RESULTS: Almost 40% of families reported experiencing
      food insecurity. Children from food-insecure households were more likely to eat
      some less healthful types of foods, including items purchased at convenience
      stores (P= .002), and food-insecure parents reported experiencing many barriers
      to accessing healthful food. Food security status was not associated with
      differences in home food availability or children's or parents' weight status.
      CONCLUSIONS: Food insecurity is prevalent among families living on the Pine Ridge
      Reservation. Increasing reservation access to food that is high quality,
      reasonably priced, and healthful should be a public health goal.

PMID- 22594741
TI  - Training primary care physicians for local health authority duties in Texas.
AB  - Only one fourth of Texas counties have a local health authority (LHA) or health
      district. Primary care physicians in the remaining counties could be trained in
      public health basics by providing an online LHA training course and courses at
      annual meetings of the Texas Medical Association and the Texas Academy of Family
      Physicians.  The Texas Department of State Health Services should develop a web
      portal for LHAs. The Texas Association of Local Health Officials should also
      provide automatic limited membership for LHAs.  These initiatives would provide
      public health training to primary care physicians and would greatly improve
      availability of public health services for the citizens of Texas.

PMID- 22594744
TI  - Oral physicians: an opportunity for dentists?

PMID- 22594743
TI  - Improving adult immunization practices using a team approach in the primary care
      setting.
AB  - OBJECTIVES: The objective of this study was to improve the immunization rates of
      primary care practices using a team approach. METHODS: Practices performed 35
      random chart abstractions at 2 time points and completed a survey about
      immunizations at baseline and 12 months after intervention. Data were collected
      for the following immunizations: influenza, pneumococcal, tetanus diphtheria
      (Td)/tetanus diphtheria pertussis (Tdap), hepatitis A, hepatitis B,
      meningococcal, varicella, herpes zoster, and human papilloma virus. Between
      baseline and after intervention, practice teams were given feedback reports and
      access to an online educational tool, and attended quality improvement coaching
      conference calls. RESULTS: Statistically significant improvements were seen for
      Td/Tdap (45.6% pre-intervention, 55.0% post-intervention; P  <= .01), herpes
      zoster (12.3% pre-intervention, 19.3% post-intervention; P <= .01), and
      pneumococcal (52.2% pre-intervention, 74.5% post-intervention; P <= .01)
      immunizations. Data also revealed an increase in the number of physicians who
      discussed herpes zoster and pneumococcal vaccinations with their patients (23.2%
      pre-intervention, 43.3% post-intervention; P <= .01 and 19.9% pre-intervention,
      43.0% post-intervention; P <= .01, respectively) as well as an increase in
      physicians using the Centers for Disease Control and Prevention immunization
      schedule (52.9% pre-intervention, 88.2% post-intervention; P <= .02).
      CONCLUSIONS: The immunization rates of the primary care practices involved in
      this study improved.

PMID- 22594745
TI  - Training physician investigators in medicine and public health research.
AB  - OBJECTIVES: We have described and evaluated the impact of a unique fellowship
      program designed to train postdoctoral, physician fellows in research at the
      interface of medicine and public health. METHODS: We developed a rigorous
      curriculum in public health content and research methods and fostered linkages
      with research mentors and local public health agencies. Didactic training
      provided the foundation for fellows' mentored research initiatives, which
      addressed real-world challenges in advancing the health status of vulnerable
      urban populations. RESULTS: Two multidisciplinary cohorts (6 per cohort)
      completed this 2-year degree-granting program and engaged in diverse public
      health research initiatives on topics such as improving pediatric care outcomes
      through health literacy interventions, reducing hospital readmission rates among
      urban poor with multiple comorbidities, increasing cancer screening uptake, and
      broadening the reach of addiction screening and intervention. The majority of
      fellows (10/12) published their fellowship work and currently have a career
      focused in public health-related research or practice (9/12). CONCLUSIONS: A
      fellowship training program can prepare physician investigators for research
      careers that bridge the divide between medicine and public health.

PMID- 22594746
TI  - The association of state law to physical education time allocation in US public
      schools.
AB  - OBJECTIVES: We examined whether public schools in states with specific and
      stringent physical education (PE) laws, as assessed by the Physical Education
      Related State Policy Classification System (PERSPCS), available on the
      Classification of Laws Associated with School Students (C.L.A.S.S.) Web site,
      reported more weekly PE time in the most recent School Health Policies and
      Programs Survey (SHPPS). METHODS: Schools (n=410) were grouped by their state's
      PERSPCS time requirement scores (none, nonspecific requirement, or specific
      requirement). Average weekly school-level PE was calculated using the SHPPS
      reported PE minutes. Weighted analyses determined if PE minutes/week differed by
      PERSPCS group. RESULTS: Schools in states with specific requirement laws averaged
      over 27 and 60 more PE minutes/week at the elementary and middle school levels,
      respectively, compared with schools within states with nonspecific laws and over
      40 and 60 more PE minutes per week, respectively, compared with elementary and
      middle schools in states with no laws. High school results were nonsignificant.
      CONCLUSIONS: Public health guidelines recommend at least 60 minutes of daily
      physical activity for children, and PE may further this goal. Strong codified law
      with specific time requirements for PE may be an important tool contributing
      toward adequate PE time and daily physical activity recommendations.

PMID- 22594747
TI  - One community's effort to control genetic disease.
AB  - In 1989, we established a small community health clinic to provide care for
      uninsured Amish and Mennonite children with genetic disorders. Over 20 years, we
      have used publicly available molecular data and sophisticated technologies to
      improve diagnostic efficiency, control laboratory costs, reduce hospitalizations,
      and prevent major neurological impairments within a rural underserved community.
      These actions allowed the clinic's 2010 operating budget of $1.5 million to save
      local communities an estimated $20 to $25 million in aggregate medical costs.
      This exposes an unsettling fact: our failure to improve the lot of most people
      stricken with genetic disease is no longer a matter of scientific ignorance or
      prohibitive costs but of choices we make about how to implement existing
      knowledge and resources.

PMID- 22594749
TI  - Oliver Mtukudzi's musical approach to HIV/AIDS.

PMID- 22594748
TI  - Results from the Data & Democracy initiative to enhance community-based
      organization data and research capacity.
AB  - OBJECTIVES: In an era of community-based participatory research and increased
      expectations for evidence-based practice, we evaluated an initiative designed to
      increase community-based organizations' data and research capacity through a 3
      day train-the-trainer course on community health assessments. METHODS: We
      employed a mixed method pre-post course evaluation design. Various data sources
      collected from 171 participants captured individual and organizational
      characteristics and pre-post course self-efficacy on 19 core skills, as well as
      behavior change 1 year later among a subsample of participants. RESULTS: Before
      the course, participants reported limited previous experience with data and low
      self-efficacy in basic research skills. Immediately after the course,
      participants demonstrated statistically significant increases in data and
      research self-efficacy. The subsample reported application of community
      assessment skills to their work and increased use of data 1 year later.
      CONCLUSIONS: Results suggest that an intensive, short-term training program can
      achieve large immediate gains in data and research self-efficacy in community
      based organization staff. In addition, they demonstrate initial evidence of
      longer-term behavior change related to use of data and research skills to support
      their community work.

PMID- 22594751
TI  - The bittersweet truth about sugar labeling regulations: they are achievable and
      overdue.
AB  - The recent Institute of Medicine recommendation to the Food and Drug
      Administration to include added sugar in a new front-of-package system provides
      new justification for reviewing outdated regulations pertinent to sugar and
      analyzing whether the government's previous resistance to sugar labeling remains
      valid given new and robust science.  I have provided an overview of US sugar
      consumption, its public health implications, and the science related to added
      sugar detection. I reviewed US and international sugar intake recommendations and
      suggested revised regulations to better inform and protect consumers.  I
      concluded by noting new directions in the area of sugar research for future
      public health policy.

PMID- 22594750
TI  - Effects of the 1997-1998 El Nino episode on community rates of diarrhea.
AB  - OBJECTIVES: To improve our understanding of climate variability and diarrheal
      disease at the community level and inform predictions for future climate change
      scenarios, we examined whether the El Nino climate pattern is associated with
      increased rates of diarrhea among Peruvian children. METHODS: We analyzed daily
      surveillance data for 367 children aged 0 to 12 years from 2 cohorts in a peri
      urban shantytown in Lima, Peru, 1995 through 1998. We stratified diarrheal
      incidence by 6-month age categories, season, and El Nino, and modeled between
      subject heterogeneity with random effects Poisson models. RESULTS: Spring
      diarrheal incidence increased by 55% during El Nino compared with before El Nino.
      This increase was most acute among children older than 60 months, for whom the
      risk of a diarrheal episode during the El Nino spring was nearly 100% greater
      (relative risk=1.96; 95% confidence interval=1.24, 3.09). CONCLUSIONS: El Nino
      associated climate variability affects community rates of diarrhea, particularly
      during the cooler seasons and among older children. Public health officials
      should develop preventive strategies for future El Nino episodes to mitigate the
      increased risk of diarrheal disease in vulnerable communities.

PMID- 22594752
TI  - Global health in conflict. Understanding opposition to vitamin A supplementation
      in India.
AB  - Vitamin A supplementation is a public health intervention that clinical trials
      have suggested can significantly improve child survival in the developing world.
      Yet, prominent scientists in India have questioned its scientific validity,
      opposed its implementation, and accused its advocates of corruption and greed. It
      is ironic that these opponents were among the pioneers of populationwide vitamin
      A supplementation for ocular health. Historically, complex interests have shaped
      vitamin A supplementation resistance in India. Local social and nutritional
      revolutions and shifting international paradigms of global health have played a
      role. Other resistance movements in Indian history, such as those in response to
      campaigns for bacillus Calmette-Guerin and novel vaccines, have been structured
      around similar themes. Public health resistance is shaped by the cultural and
      political context in which it develops. Armed with knowledge of the history of a
      region and patterns of past resistance, public health practitioners can better
      understand how to negotiate global health conflicts.

PMID- 22594753
TI  - Community health worker encounter forms: a tool to guide and document patient
      visits and worker performance.
AB  - OBJECTIVES: We explored the benefits of using community health worker (CHW)
      encounter forms to collect data on patient interactions and assessed the
      effectiveness of these forms in guiding and directing interactions. METHODS: A 1
      page standardized encounter form was developed to document topics discussed
      during visits with diabetes patients. A portion of the form was designed to be
      used as a script to guide the interaction and assist patients in setting
      appropriate self-management goals. Data were also collected via CHW work logs and
      interviews with CHWs and their supervisors to validate findings. RESULTS: Data
      were collected for 1198 interactions with 540 patients at 6 community health
      centers. Self-management goals were set during 62% of encounters. With respect to
      the most recent self-management goal set, patients who had set a challenging goal
      were more likely to be in the action stage of change than in other stages. Work
      logs revealed that CHWs engaged in a number of activities not involving direct
      patient interactions and thus not captured on encounter forms. CONCLUSIONS:
      Evaluating and monitoring CHWs' daily activities has been challenging. Encounter
      forms have great potential for documenting the work of CHWs with patients.

PMID- 22594754
TI  - Research participation as work: comparing the perspectives of researchers and
      economically marginalized populations.
AB  - We examined the historical and regulatory framework of research with human
      participants in the United States, and described some possible unintended
      consequences of this framework in the context of paying young injection drug
      users for their time participating in behavioral and medical research. We drew
      upon our own experiences while conducting a long-running epidemiological study of
      hepatitis C virus infection.  We found that existing ethical and regulatory
      framings of research participation may lead to injustices from the perspectives
      of research participants.  We propose considering research participation as a
      specialized form of work and the use of community advisory boards to facilitate
      discussion about appropriate compensation for research participation among
      economically marginalized populations.

PMID- 22594755
TI  - Raymond B. Fosdick (1883-1972): ardent advocate of internationalism.

PMID- 22594756
TI  - Pandemicity and severity are separate constructs.

PMID- 22594758
TI  - National Institutes of Health approaches to dissemination and implementation
      science: current and future directions.
AB  - To address the vast gap between current knowledge and practice in the area of
      dissemination and implementation research, we address terminology, provide
      examples of successful applications of this research, discuss key sources of
      support, and highlight directions and opportunities for future advances. There is
      a need for research testing approaches to scaling up and sustaining effective
      interventions, and we propose that further advances in the field will be achieved
      by focusing dissemination and implementation research on 5 core values: rigor and
      relevance, efficiency, collaboration, improved capacity, and cumulative
      knowledge.

PMID- 22594759
TI  - From practice to policy: the intersection of government and law (what's in a
      name?).

PMID- 22594760
TI  - Pharmacogenomics of third-generation aromatase inhibitors.
AB  - INTRODUCTION: Breast cancer is a common, life-threatening disease among women.
      Contemporary hormonal therapy with third-generation aromatase inhibitors for
      estrogen-receptor-positive breast cancers in postmenopausal women is still facing
      the challenge of interpatient variability in therapeutic response and intensity
      of adverse effects. AREAS COVERED: This review highlights up-to-date literature
      regarding genomic findings in the literature pertaining to anastrozole,
      exemestane and letrozole metabolism, as well as the drug target aromatase.
      Genetic polymorphisms in phase I and II aromatase inhibitor metabolizing enzymes
      that contribute to altered responses among different patient genotypes are
      discussed. Similarly, aromatase CYP19A1 functional genetic polymorphisms are
      presented in correlation to altered aromatase activity, disease prognosis and
      severity of aromatase inhibitor adverse effects. EXPERT OPINION: The field of
      pharmacogenomics has shown remarkable progress over the last few years, notably
      in cancer. However, large comprehensive genotyping studies, evaluated under
      clinical settings, are still needed to unravel the potential impact of aromatase
      inhibitor pharmacogenomics on breast cancer treatment, monitoring and predicting
      adverse effects.

PMID- 22594761
TI  - Factors that influence survival in a probable Alzheimer disease cohort.
AB  - INTRODUCTION: This longitudinal study examined multiple factors that influence
      survival in a cohort of Alzheimer patients followed over two decades. METHODS:
      Time to death after symptom onset was determined in 641 probable AD patients who
      were evaluated annually until death or loss to follow-up, and information was
      entered into a longitudinal database. Date of death was available for everyone
      including those eventually lost. Baseline variables included age, sex, race,
      disease severity, a calculated index of rate of initial cognitive decline from
      symptom onset to cohort entry (pre-progression rate or PPR), years of education,
      and medical comorbidities (diabetes, hypertension, hyperlipidemia, coronary
      disease, cerebrovascular disease). Multivariable Cox proportional hazard
      regression analysis was used to analyze the baseline and/or time dependent
      association in Mini-mental Status Exam (MMSE) severity, Physical Self Maintenance
      Scale (PSMS), Persistency Index (PI) of exposure to antipsychotic and
      antidementia drugs, and psychotic symptoms (hallucinations, delusions) with
      mortality. RESULTS: Baseline covariates significantly associated with increased
      survival were younger age (p = .0016), female sex (p = .0001), and a slower PPR
      (p < .0001). Overall disease severity at baseline, medical comorbidities, and
      education did not influence time to death. Time-dependent changes in
      antipsychotic drug use, development of psychotic symptoms, antidementia drug use,
      and observed MMSE change were not predictive. In the final model the only time
      dependent covariate that significantly decreased survival was worsening of
      functional ability on the PSMS (hazard ratio = 1.10; CI: 1.07-1.11). CONCLUSIONS:
      In this large AD cohort survival is influenced by age, sex, and the development
      of functional disability during follow-up. The most important predictor of
      mortality was a faster rate of cognitive decline at the initial patient visit
      (PPR). The currently available antidementia drugs do not prolong survival in
      Alzheimer patients.

PMID- 22594762
TI  - Multiphase chemical kinetics of NO3 radicals reacting with organic aerosol
      components from biomass burning.
AB  - Multiphase reactions with nitrate radicals are among the most important chemical
      aging processes of organic aerosol particles in the atmosphere especially at
      nighttime. Reactive uptake of NO(3) by organic compounds has been observed in a
      number of studies, but the pathways of mass transport and chemical reaction
      remained unclear. Here we apply kinetic flux models to experimental NO(3)
      exposure studies. The model accounts for gas phase diffusion within a cylindrical
      flow tube, reversible adsorption of NO(3), surface-bulk exchange, bulk diffusion,
      and chemical reactions from the gas-condensed phase interface to the bulk. We
      resolve the relative contributions of surface and bulk reactions to the uptake of
      NO(3) by levoglucosan and abietic acid, which serve as surrogates and molecular
      markers of biomass burning aerosol (BBA). Applying the kinetic flux model, we
      provide the first estimate of the diffusion coefficient of NO(3) in amorphous
      solid organic matrices (10(-8)-10(-7) cm(2) s(-1)) and show that molecular
      markers are well-conserved in the bulk of solid BBA particles but undergo rapid
      degradation upon deliquescence/liquefaction at high relative humidity, indicating
      that the observed concentrations and subsequent apportionment of the biomass
      burning source could be significantly underestimated.

PMID- 22594763
TI  - Incidence of visual impairment due to cataract, diabetic retinopathy and trachoma
      in indigenous Australians within central Australia: the Central Australian Ocular
      Health Study.
AB  - BACKGROUND: To estimate the incidence and causes of visual impairment for the
      purposes of service provision among the indigenous Australian population within
      central Australia from its most common causes, namely cataract, diabetic
      retinopathy and trachoma. DESIGN: Clinic-based cohort study. PARTICIPANTS: One
      thousand eight hundred eighty four individuals aged >=20 years living in one of
      30 remote communities within the statistical local area of 'Central Australia'.
      METHODS: From those initially recruited, 608 (32%) participants were reviewed
      again between 6 months and 3 years (median 2 years). Patients underwent Snellen
      visual acuity testing and subjective refraction. Following this, an assessment of
      their anterior and posterior segments was made. Baseline results were compared
      with those who were reviewed. MAIN OUTCOME MEASURES: The annual incidence rates
      and causes of visual impairment (vision worse than Snellen visual acuity 6/12 in
      at least one eye). RESULTS: The incidence of visual impairment in at least one
      eye was 6.6%, 1.2% and 0.7% per year for cataract, diabetic retinopathy and
      trachoma, respectively (7.9%, 1.5% and 0.7% per year for those aged >=40 years).
      Advancing age was the main risk factor common to all three. CONCLUSION: It is
      important to be mindful not only of the prevalence of disease in a community but
      also of the rate at which new cases are occurring when allocating resources to
      address the ocular health needs of this region. Compared with historical data,
      diabetic retinopathy is emerging as a new and increasing threat to vision in this
      population.

PMID- 22594764
TI  - Grandiose and vulnerable narcissism and the DSM-5 pathological personality trait
      model.
AB  - The Diagnostic and Statistical Manual of Personality Disorders (4th ed., American
      Psychiatric Association, 2000) personality disorders (PDs) that will be included
      in the DSM-5 will be diagnosed in an entirely different manner; the explicit
      criterion sets will be replaced with impairments in self and interpersonal
      functioning and personality traits from a 25-trait dimensional model of
      personality pathology. From a trait perspective, narcissistic personality
      disorder (NPD), the focus of this study, is assessed using 2 specific traits:
      grandiosity and attention seeking. Using a sample collected online from Amazon's
      Mechanical Turk (MTurk; N=306), we examined the relations among traits from a new
      measure of DSM-5's trait model--the Personality Inventory for DSM-5 (PID5;
      Krueger, Derringer, Markon, Watson, & Skodol, in press)--and grandiose and
      vulnerable narcissism. The 25 traits from PID5 captured a significant portion of
      the variance in grandiose and vulnerable factors, although the 2 specific facets
      designated for the assessment of NPD fared substantially better in the assessment
      of grandiose rather than vulnerable narcissism. These results are discussed in
      the context of improving the DSM-5's ability to capture both narcissism
      dimensions.

PMID- 22594766
TI  - Ultrasound guided piriformis injection with confirmation of needle placement
      through electromyography.

PMID- 22594765
TI  - Nutritional regulation of muscle protein synthesis with resistance exercise:
      strategies to enhance anabolism.
AB  - Provision of dietary amino acids increases skeletal muscle protein synthesis
      (MPS), an effect that is enhanced by prior resistance exercise. As a
      fundamentally necessary process in the enhancement of muscle mass, strategies to
      enhance rates of MPS would be beneficial in the development of interventions
      aimed at increasing skeletal muscle mass particularly when combined with chronic
      resistance exercise. The purpose of this review article is to provide an update
      on current findings regarding the nutritional regulation of MPS and highlight
      nutrition based strategies that may serve to maximize skeletal muscle protein
      anabolism with resistance exercise. Such factors include timing of protein
      intake, dietary protein type, the role of leucine as a key anabolic amino acid,
      and the impact of other macronutrients (i.e. carbohydrate) on the regulation of
      MPS after resistance exercise. We contend that nutritional strategies that serve
      to maximally stimulate MPS may be useful in the development of nutrition and
      exercise based interventions aimed at enhancing skeletal muscle mass which may be
      of interest to elderly populations and to athletes.

PMID- 22594767
TI  - P1 and beyond: functional separation of multiple emotion effects in word
      recognition.
AB  - Event-related potentials (ERPs) revealed effects of emotional meaning on word
      recognition at distinguishable processing stages, in rare cases even in the P1
      time range. However, the boundary conditions of these effects, such as the roles
      of different levels of linguistic processing or the relative contributions of the
      emotional valence and arousal dimensions, remain to be fully understood. The
      present study addresses this issue by employing two tasks of different processing
      demands on words that orthogonally varied in their emotional valence and arousal.
      Effects of emotional valence in ERPs were evident from 100 ms after word onset
      and showed a task-insensitive processing advantage for positive words. Early
      posterior negativity (EPN) effects to high-arousing words were limited to the
      lexical decision task, corroborating recent reports that suggested that
      perceptual processing as reflected in the EPN might not be as automatic as
      previously assumed.

PMID- 22594768
TI  - Smart reticulated hydrogel of functionally decorated gellan copolymer for
      prolonged delivery of salbutamol sulphate to the gastro-luminal milieu.
AB  - A partially hydrolysed poly(acrylamide)-grafted-gellan (HPAmGG) copolymer was
      synthesised and characterised. Temperature- and concentration-dependent rheology
      and gel-like property of Gelrite gellan (GG) disappeared in HPAmGG copolymer.
      Smart HPAmGG hydrogel was fabricated with variation in aluminium chloride
      (AlCl(3)) strength and initial drug loading. The hydrogel reticulates seemed
      spherical and showed a maximum of ~65% drug retention, but the assay was ~22%
      lower for GG hydrogel. The drug release rate was inversely proportional to
      AlCl(3) strength in simulated intestinal milieu (pH 7.4), but approximated a
      proportional relationship with drug load. HPAmGG hydrogel liberated only 10-17%
      content in simulated gastric milieu (pH 1.2) in 2 h. The release data correlated
      well with the pH-dependent swelling of hydrogel and indicated the anomalous drug
      diffusion mechanism. Differential scanning calorimetry, X-ray diffraction, and
      high-performance liquid chromatography analyses confirmed the amorphous nature of
      the drug and its stability in fresh and aged hydrogel. Hence, smart HPAmGG
      hydrogel had the potential to prolong drug release mimicking the variable pH of
      the gastrointestinal tract.

PMID- 22594770
TI  - The electronic cigarette: what proportion of smokers have tried it and how many
      use it regularly?

PMID- 22594769
TI  - Phase 1 dose-escalation trial of clofarabine followed by escalating dose of
      fractionated cyclophosphamide in adults with relapsed or refractory acute
      leukaemias.
AB  - The prognosis of patients with relapsed and refractory acute leukaemia (RRAL) is
      very poor. Forty patients with RRAL were enroled [28 acute myeloid leukaemia
      (AML), 12 acute lymphoblastic leukaemia (ALL)] in this Phase 1 dose-escalation
      trial of daily-infused clofarabine (CLO) followed by cyclophosphamide (CY) for
      four consecutive days (CLO-CYx4). The median age was 48.5 years. The median
      number of prior regimens was 2 (range 1-5), and 6/40 patients (15%) had prior
      allogeneic haematopoietic stem cell transplant. 28/40 patients (70%) had adverse
      genetic features. 6/40 patients (15%) died within 60 d of induction (two
      infections, four progressive disease). The average time to neutrophil recovery
      (absolute neutrophil count >=0.5 * 10(9) /l was 34 d, (range, 17-78). The overall
      response rate (ORR) was 33% (13/40), with seven complete remissions (18%), four
      complete remissions with incomplete recovery of blood counts (10%), and two
      partial remissions (5%). ORR was 25% (7/28), and 50% (6/12), for AML and ALL
      respectively. Notably, the clinical responses were independent of dose level.
      7/17 patients (41%) exhibited CLO-mediated enhancement of CY-induced DNA, which
      was associated with, but not necessary for, improved clinical outcomes. In
      summary, the CLO-CYx4 regimen was well tolerated and had activity in patients
      with RRAL, especially relapsed ALL. Therefore, CLO-CYx4 can be considered a
      salvage therapy for adults with RRALs, and warrants further investigations.

PMID- 22594771
TI  - Musings of an erstwhile plant pathologist.

PMID- 22594772
TI  - Phase transfer of CdS nanocrystals mediated by heptamine beta-cyclodextrin.
AB  - A fundamental and systematic study on the fabrication of a supramolecularly
      assembled nanostructure of an organic ligand-capped CdS nanocrystal (NC) and
      multiple heptamine beta-cyclodextrin ((NH(2))(7)betaCD) molecules in aqueous
      solution has been here reported. The functionalization process of presynthesized
      hydrophobic CdS NCs by means of (NH(2))(7)betaCD has been extensively
      investigated by using different spectroscopic and structural techniques, as a
      function of different experimental parameters, such as the composition and the
      concentration of CD, the concentration of CdS NCs, the nature of the NC surface
      capping ligand (oleic acid and octylamine), and the organic solvent. The
      formation of a complex based on the direct coordination of the (NH(2))(7)betaCD
      amine groups at the NC surface has been demonstrated and found responsible for
      the CdS NC phase transfer process. The amine functional group in (NH(2))(7)betaCD
      and the appropriate combination of pristine capping agent coordinating the NC
      surface and a suitable solvent have been found decisive for the success of the
      CdS NC phase transfer process. Furthermore, a layer-by-layer assembly experiment
      has indicated that the obtained (NH(2))(7)betaCD functionalized CdS NCs are still
      able to perform the host-guest chemistry. Thus, they offer a model of a
      nanoparticle-based material with molecular receptors, useful for bio
      applications.

PMID- 22594773
TI  - Significant stabilization of ribonuclease A by additive effects.
AB  - Among the strategies that employ genetic engineering to stabilize proteins, the
      introduction of disulfide bonds has proven to be a very potential approach. As,
      however, the replacement of amino acid residues by cysteines and the subsequent
      formation of the covalent bond can result in a severe deformation of the parental
      protein structure, the stabilization effect is strongly context dependent.
      Alternatively, the introduction of charged amino acid residues at the surface,
      which may result in the formation of extra ionic interactions or hydrogen bonds,
      provide propitious means for protein stabilization. The generation of an extra
      disulfide bond between residues 4 and 118 in ribonuclease A had resulted in a
      stabilization by 6  degrees C or 7 kJ mol(-1), which was mainly caused by a
      deceleration of the unfolding reaction [Pecher, P. & Arnold, U. (2009) Biophys
      Chem, 141, 21-28]. Here, Asp83 was replaced by Glu resulting in a comparable
      stabilization. Moreover, combination of both mutations led to an additive effect
      and the resulting ribonuclease A variant (T(m) ~ 76  degrees C, DeltaG degrees  ~
      53 kJ mol(-1)) is the most stable ribonuclease A variant described so far. The
      analysis of the crystal structure of A4C/D83E/V118C-ribonuclease A reveals the
      formation of a salt bridge between the gamma-carboxyl group of Glu83 and the
      epsilon-amino group of Lys104.

PMID- 22594774
TI  - Histological evolution of hepatitis C virus infection after renal
      transplantation.
AB  - BACKGROUND: information regarding histological progression of hepatitis C after
      renal transplant (RTx) is scarce. AIMS: To analyze clinical and laboratory
      evolution and histological progression of hepatitis C in patients evaluated
      before and after RTx. METHODS: Twenty-two HCV-infected patients submitted to
      liver biopsy pre- and post-RTx were included. A semiquantitative analysis of
      necroinflammatory activity and fibrosis staging was performed and the two
      biopsies were compared. RESULTS: Patients were mostly men (73%) with mean age of
      36+/-9 yr. Time post-transplant was 4+/-2 yr and time between biopsies was 5+/-2
      yr. An elevation of alanine aminotransferase (p=0.041) and aspartate
      aminotransferase (p=0.004) levels was observed in the post-transplant period.
      Fibrosis progression after renal transplantation was observed in 11 (50%) of the
      patients, and necroinflammatory activity worsening was observed in 7 (32%) of the
      patients. The histological progression occurred even among those without
      significant histological lesions in pre-transplant biopsy. CONCLUSION: The
      findings of this study suggest that the practice of indicating treatment in the
      pre-transplant phase based mainly on histological disease should be revised,
      because a high proportion of patients present disease progression. Because
      interferon cannot be used safely after RTx, treatment should be indicated for all
      ESRD patients with hepatitis C.

PMID- 22594775
TI  - Microimplant-based mandibular advancement therapy for the treatment of snoring
      and obstructive sleep apnea: a prospective study.
AB  - OBJECTIVE: To investigate the efficacy of orthodontic microimplant-based
      mandibular advancement therapies for the treatment of snoring and obstructive
      sleep apnea (OSA) in adult patients. MATERIALS AND METHODS: Ten adult OSA
      patients (seven men, three women; mean age 60.00 +/- 9.25 years) were each
      treated with two mandibular orthodontic microimplants attached to a customized
      reverse face mask for mandibular advancement. Pretreatment and posttreatment
      outcome measures of microimplant mobility, apnea-hypopnea index, snoring,
      respiratory movement, and Epworth sleepiness scores were evaluated after 6
      months. RESULTS: Highly significant reductions in the apnea-hypopnea index,
      snoring, and sleep variables were observed. Sixteen of the 20 (80%) microimplants
      were stable and showed no mobility, and four (20%) demonstrated grade 1 or 2
      mobility and required removal and reinsertion of a new microimplant. CONCLUSIONS:
      Favorable reductions in sleep variables highlight the potential of microimplant
      based mandibular advancement therapy as an alternative treatment modality for OSA
      patients who cannot tolerate continuous positive airway pressure and oral
      appliance therapy.

PMID- 22594776
TI  - The impact of personality on adult patients' adjustability to orthodontic
      appliances.
AB  - OBJECTIVE: To evaluate the impact of psychological traits on patients' choice of
      orthodontic appliances and their adjustability to orthodontic treatment.
      MATERIALS AND METHODS: The sample consisted of 68 adult patients divided into
      three groups (28 buccal, 19 lingual, and 21 clear aligners). Prior to treatment
      participants filled out the Brief Symptom Inventory to assess symptoms of mental
      distress and the Narcissistic Vulnerability Scale to assess narcissistic
      personality traits. During the first week after appliance delivery and on day 14,
      patients completed a Health-Related Quality of Life questionnaire to assess their
      perception of pain and four areas of dysfunction. The correlation between
      personality traits and patients' reaction to treatment was evaluated. RESULTS:
      Somatization was the only trait that affected the choice of lingual and clear
      aligner appliance. Reduced self-esteem regulation was associated with increased
      pain in all patients, while exploitation was associated with pain in lingual
      patients. Narcissistic vulnerability slightly influenced patients' adaptability
      to orthodontic appliances. Although adjustability to lingual appliances was the
      most difficult, only two parameters were affected by personality features. In the
      buccal group, adjustability was affected by numerous parameters. Adaptation to
      the clear aligner appliance was relatively uneventful and least affected by
      psychological features. CONCLUSION: Anxious individuals tend to prefer lingual
      and clear aligner appliances. The selection of lingual and clear aligner
      appliances governs the patient's response and recovery process, leaving little
      room for the effect of psychological features. On the other hand, the buccal
      appliance allows for greater impact of personality traits on adjustability.

PMID- 22594777
TI  - Theoretical prediction of S-H bond rupture in methanethiol upon interaction with
      gold.
AB  - Organic thiols are known to react with gold surface to form self-assembled
      monolayers (SAMs), which can be used to produce materials with highly attractive
      properties. Although the structure of various SAMs is widely investigated, some
      aspects of their formation still represent a matter of debate. One of these
      aspects is the mechanism of S-H bond dissociation in thiols upon interaction with
      gold. This work presents a new suggestion for this mechanism on the basis of DFT
      study of methanethiol interaction with a single gold atom and a Au(20) cluster.
      The reaction path of dissociation is found to be qualitatively independent of the
      model employed. However, the highest activation barrier of S-H bond dissociation
      on the single gold atom (12.9 kcal/mol) is considerably lower than that on the
      Au(20) cluster (28.9 kcal/mol), which can be attributed to the higher extent of
      gold unsaturation. The energy barrier of S-H cleavage decreases by 4.6 kcal/mol
      in the presence of the second methanethiol molecule at the same adsorption site
      on the model gold atom. In the case of the Au(20) cluster we have observed the
      phenomenon of hydrogen transfer from one methanethiol molecule to another, which
      allows reducing the energy barrier of dissociation by 9.1 kcal/mol. This
      indicates the possibility of the "relay" hydrogen transfer to be the key step of
      the thiol adsorption observed for the SAMs systems.

PMID- 22594778
TI  - Linear milia en plaque on the central face: an acquired skin rash following
      Blaschko's lines?

PMID- 22594779
TI  - Cytochrome 1A1 and 1B1 gene diversity in the Zanzibar islands.
AB  - Amodiaquine (AQ) is a 4-aminoquinoline widely used in the treatment of malaria as
      part of the artemisinin combination therapy (ACT). AQ is metabolised towards its
      main metabolite desethylamodiaquine mainly by cytochrome P450 2C8 (CYP2C8).
      CYP1A1 and CYP1B1 play a minor role in the metabolism but they seem to be
      significantly involved in the formation of the short-lived quinine-imine. To
      complete the genetic variation picture of the main genes involved in AQ
      metabolism in the Zanzibar population, previously characterised for CYP2C8, we
      analysed in this study CYP1A1 and CYP1B1 main genetic polymorphisms. The results
      obtained show a low frequency of the CYP1A1*2B/C allele (2.4%) and a high
      frequency of CYP1B1*6 (approximately 42%) followed by CYP1B1*2 (approximately
      27%) in Zanzibar islands. Genotype data for CYP1A1 and CYP1B1 show a low
      incidence of fast metabolisers, revealing a relatively safe genetic background in
      Zanzibar's population regarding the appearance of adverse effects.

PMID- 22594780
TI  - Dietary management of urea cycle disorders: UK practice.
AB  - BACKGROUND: There is no published data describing UK dietary management of urea
      cycle disorders (UCD). The present study describes dietary practices in UK
      inherited metabolic disorder (IMD) centres. METHODS: Cross-sectional data from 16
      IMD centres were collected by a questionnaire describing the management of UCD
      patients on prescribed protein-restricted diets. RESULTS: One hundred and seventy
      five patients [N-acetylglutamate synthase deficiency, n = 3; carbamoyl phosphate
      synthase deficiency (CPS), n = 8; ornithine transcarbamoylase deficiency (OTC), n
      = 75; citrullinaemia, n = 41; argininosuccinic aciduria (ASA), n = 36; arginase
      deficiency, n = 12] were reported; 70% (n = 123) aged 0-16 years; 30% (n = 52)
      >16 years. Prescribed median protein intake decreased with age (0-6 months: 2 g
      kg(-1) day(-1); 7-12 months: 1.6 g kg(-1) day(-1); 1-10 years: 1.3 g kg(-1) day(
      1); 11-16 years: 0.9 g kg(-1) day(-1) and >16 years: 0.8 g kg(-1) day(-1)) with
      little variation between disorders. Adult protein prescription ranged 0.4-1.2 g
      kg(-1) day(-1) (40-60 g day(-1)). In the previous 2 years, 30% (n = 53) were
      given essential amino acid supplements (EAAs) (CPS, n = 2; OTC, n = 20;
      citrullinaemia, n = 15; ASA, n = 7; arginase deficiency, n = 9). EAAs were
      prescribed for low plasma quantitative essential amino acids (n = 13 centres);
      inadequate natural protein intake (n = 11) and poor metabolic control (n = 9).
      From diagnosis, one centre prescribed EAAs for all patients and one centre for
      severe defects only. Only 3% (n = 6) were given branch chain amino acid
      supplements. Enteral feeding tubes were used by 25% (n = 44) for feeds and 3% (n
      = 6) for medications. Oral energy supplements were prescribed in 17% (n = 30) of
      cases. CONCLUSIONS: In the UK, protein restriction based on World Health
      Organization 'safe intakes of protein', is the principle dietary treatment for
      UCD. EAA supplements are prescribed mainly on clinical need. Multicentre
      collaborative research is required to define optimal dietary treatments.

PMID- 22594781
TI  - Darunavir : a nonpeptidic protease inhibitor for antiretroviral-naive and
      treatment-experienced adults with HIV infection.
AB  - INTRODUCTION: Darunavir , a nonpeptidic inhibitor of the HIV-1 protease with
      potent activity against resistant virus, was initially approved by the FDA (2006)
      and the EMA (2007) for the treatment of antiretroviral-experienced adults, and
      later for naive adults. Darunavir/ritonavir (600/100 mg twice daily, ideally
      given with two other active antiretrovirals) demonstrated superior efficacy
      compared to lopinavir/ritonavir and other protease inhibitors in highly
      experienced patients. Darunavir/ritonavir (800/100 mg once daily) was
      demonstrated to be safe and effective for the treatment of naive patients and
      those with limited darunavir resistance-associated mutations (RAMs). Because
      darunavir must be coadministered with ritonavir, cytochrome P450 drug-drug
      interactions can be problematic. AREAS COVERED: The chemistry, pharmacokinetics,
      pharmacodynamics, efficacy and safety of darunavir are reviewed in this paper. A
      PubMed search was conducted using the search terms 'randomized', 'darunavir' and
      'efficacy'. Review articles and studies that primarily focused on other drugs
      were excluded. EXPERT OPINION: Because darunavir exhibits efficacy against virus
      with significant protease inhibitor resistance mutations, it is critically
      important in the treatment of experienced patients, although viral suppression
      rates may be lower in those with a high baseline viral load or a greater number
      of cumulative darunavir RAMs. Darunavir/ritonavir is efficacious and well
      tolerated as a once-daily regimen in naive patients.

PMID- 22594782
TI  - Immobilization of Hg(II) by coprecipitation in sulfate-cement systems.
AB  - Uptake and molecular speciation of dissolved Hg during formation of Al- or Fe
      ettringite-type and high-pH phases were investigated in coprecipitation and
      sorption experiments of sulfate-cement treatments used for soil and sediment
      remediation. Ettringite and minor gypsum were identified by XRD as primary phases
      in Al systems, whereas gypsum and ferrihydrite were the main products in Hg-Fe
      precipitates. Characterization of Hg-Al solids by bulk Hg EXAFS, electron
      microprobe, and microfocused-XRF mapping indicated coordination of Hg by Cl
      ligands, multiple Hg and Cl backscattering atoms, and concentration of Hg as
      small particles. Thermodynamic predictions agreed with experimental observations
      for bulk phases, but Hg speciation indicated lack of equilibration with the final
      solution. Results suggest physical encapsulation of Hg as a polynuclear
      chloromercury(II) salt in ettringite as the primary immobilization mechanism. In
      Hg-Fe solids, structural characterization indicated Hg coordination by O atoms
      only and Fe backscattering atoms that is consistent with inner-sphere
      complexation of Hg(OH)(2)(0) coprecipitated with ferrihydrite. Precipitation of
      ferrihydrite removed Hg from solution, but the resulting solid was sufficiently
      hydrated to allow equilibration of sorbed Hg species with the aqueous solution.
      Electron microprobe XRF characterization of sorption samples with low Hg
      concentration reacted with cement and FeSO(4) amendment indicated correlation of
      Hg and Fe, supporting the interpretation of Hg removal by precipitation of an
      Fe(III) oxide phase.

PMID- 22594783
TI  - The MAP2K5-linked SNP rs2241423 is associated with BMI and obesity in two cohorts
      of Swedish and Greek children.
AB  - BACKGROUND: Recent genome-wide association studies have identified a single
      nucleotide polymorphism within the last intron of MAP2K5 associated with a higher
      body mass index (BMI) in adults. MAP2K5 is a component of the MAPK-family
      intracellular signaling pathways, responding to extracellular growth factors such
      as brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF). In
      this study, we examined the association of this variant in two cohorts of
      children from Sweden and Greece. METHODS: We examine the association of rs2241423
      to BMI in a cohort of 474 Swedish children admitted for treatment of childhood
      obesity and 519 children matched for gender, ethnicity and socioeconomic
      background from the Stockholm area, as well as a cross-sectional cohort of 2308
      Greek school children (Healthy Growth Study). Children were genotyped using a
      predesigned TaqMan polymorphism assay. Logistic regression was used to test for
      an association of rs2241423 to obesity in the cohort of Swedish children. Linear
      regression was used to test for an association of rs2241423 to BMI z-score and
      phenotypic measurements of body adiposity in the cohort of Greek children. Models
      were adjusted for age and gender. In the cohort of Greek children the model was
      also adjusted for stage of pubertal development. RESULTS: The minor allele of
      rs2241423, allele A, was associated with a protective effect against obesity in
      the cohort of Swedish children (p = 0.029, OR = 0.79 (95% CI: 0.64-0.98)), and
      with a lower BMI z-score in the cohort of Greek children (p = 0.028, beta = 
      0.092). No association to phenotypic measurements of body fat distribution could
      be observed in our study. CONCLUSIONS: rs2241423 was associated with BMI and
      obesity in two independent European cohorts suggesting a role for MAP2K5 in early
      weight regulation.

PMID- 22594784
TI  - Test-retest reliability of an fMRI paradigm for studies of cardiovascular
      reactivity.
AB  - We examined the reliability of measures of fMRI, subjective, and cardiovascular
      reactions to standardized versions of a Stroop color-word task and a multisource
      interference task. A sample of 14 men and 12 women (30-49 years old) completed
      the tasks on two occasions, separated by a median of 88 days. The reliability of
      fMRI BOLD signal changes in brain areas engaged by the tasks was moderate, and
      aggregating fMRI BOLD signal changes across the tasks improved test-retest
      reliability metrics. These metrics included voxel-wise intraclass correlation
      coefficients (ICCs) and overlap ratio statistics. Task-aggregated ratings of
      subjective arousal, valence, and control, as well as cardiovascular reactions
      evoked by the tasks showed ICCs of 0.57 to 0.87 (ps < .001), indicating moderate
      to-strong reliability. These findings support using these tasks as a battery for
      fMRI studies of cardiovascular reactivity.

PMID- 22594785
TI  - Characterization of lacrimal sac histology: an immunohistochemical study.
AB  - BACKGROUND: A prospective observational study in a university hospital setting to
      study the immunohistochemical (IHC) characteristics of non-neoplastic human
      lacrimal sac epithelium. METHODS: Twenty paraffin-embedded specimens of human
      lacrimal sac were studied using monospecific monoclonal antibodies to 34 beta
      E12, cell adhesion molecule (CAM 5.2), epithelial membrane antigen (EMA),
      cytokeratins (CK) 7 and 20, estrogen receptor and progesterone receptor. The
      distribution and histologic location of IHC staining were examined qualitatively,
      and the IHC stains scored as positive (+) or negative (-). RESULTS: The
      haematoxylin-eosin stains were reviewed for tissue morphology. All 20 specimens
      were positive for 34 beta E12, CAM 5.2, EMA and CK 7 and negative for CK 20,
      estrogen receptor and progesterone receptor. CONCLUSION: To our knowledge, this
      is the first study to characterize the IHC properties of human lacrimal sac
      epithelium. This epithelium appears to possess consistent IHC properties as it
      stains for 34 beta E12, CAM 5.2, EMA and CK 7 and this information would be
      potentially useful in differentiating tumours arising in the region of the
      lacrimal sac.

PMID- 22594786
TI  - Development of the Global Disability Scale (Glo.Di.S): preliminary results.
AB  - BACKGROUND: The assessment of functioning and disability is an important part of
      the clinical evaluation, since it measures disease burden and reflects the
      effectiveness of therapeutic planning and interventions. The aim of the current
      study was to develop such a self-report instrument on the basis of a review of
      the literature, and compatible with the WHO approach. MATERIAL AND METHODS: The
      review of the literature led to the development of the Global Disability Scale
      (Glo.Di.S) with 25 items assessing different aspects of disability. The study
      sample included 728 persons from vulnerable populations (homeless, jobless, very
      low income, single parent families etc.; (29.12% males and 70.88% females; aged
      55.96 +/- 15.22 years). The protocol included also the STAI and the CES-D. The
      statistical analysis included factor analysis item analysis and ANCOVA. RESULTS:
      The factor analysis revealed the presence of 4 factors explaining 71% of total
      variance (Everyday functioning, Social and interpersonal functioning, Severity
      and Mental disability). Chronbach's alpha for the whole scale was 0.95 and for
      subscales were 0.74-0.94. DISCUSSION: The results of the current study suggest
      that the Glo.Di.S. has the potential to serve as a reliable and valid tool for
      assessing functioning and disability. Further research is needed to prove that it
      could be useful across countries, populations and diseases, and whether it
      provides data that are culturally meaningful and comparable. It can be used in
      surveys and in clinical research settings and it can generate information of use
      in evaluating health needs and the effectiveness of interventions to reduce
      disability and improve health.

PMID- 22594787
TI  - Effect of incorporating prebiotics in coating materials for the
      microencapsulation of Saccharomyces boulardii.
AB  - The objective of this study was to microencapsulate Saccharomyces boulardii using
      the emulsion technique. To microencapsulate the yeast, alginate sodium blended
      with inulin and mucilage from Opuntiaficus-indica was used as a coating material.
      The textural properties of the gels formed by the encapsulating materials and the
      in vitro viability of the yeast strain in the simulated conditions were studied.
      Textural profile analyses of the gels revealed differences (p < 0.05) in hardness
      because alginate produced stronger gels, whereas the incorporation of other
      hydrocolloids with alginate decreased gel strength and resulted in a more
      uniform, cohesive gel matrix. When alginate was blended with mucilage and inulin,
      encapsulated yeast presented higher counts and more viable cells, as compared to
      free yeast following 30 days of storage at 4  degrees C. Encapsulated and free
      yeast had 76.1% and 63.3%, respectively, of cell viability after 35 days of
      storage.

PMID- 22594788
TI  - The role of inflammation and cardiovascular disease risk on microvascular and
      macrovascular endothelial function in patients with rheumatoid arthritis: a cross
      sectional and longitudinal study.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is associated with an increased risk for
      cardiovascular disease (CVD), and it has been postulated that RA disease-related
      inflammation contributes to endothelial dysfunction. The aim of the present work
      was to examine predictors (RA-related and CVD risk factors) and anti-tumor
      necrosis factor-alpha (anti-TNF-alpha) treatment effects on endothelial function
      in different vascular beds. METHODS: Microvascular endothelial function (laser
      Doppler imaging with iontophoresis of acetylcholine and sodium-nitroprusside),
      and macrovascular endothelial function (flow-mediated dilatation and glyceryl
      trinitrate-mediated dilatation) were analyzed in parallel with disease activity.
      Individual CVD risk factors and global CVD risk were assessed cross-sectionally
      in 99 unselected RA patients and longitudinally (baseline, 2 weeks, and 3 months)
      in 23 RA patients commencing anti-TNF-alpha therapy. RESULTS: In this cross
      sectional study, regression analyses revealed that markers of RA disease-related
      inflammation were not associated with microvascular or macrovascular endothelium
      dependent function (P > 0.05); global CVD risk inversely correlated with
      microvascular endothelium-dependent function (P < 0.01) and with macrovascular
      endothelium-independent function (P < 0.01). In the longitudinal study, only
      microvascular endothelium-dependent function showed an improvement after 2 weeks
      of anti-TNF-alpha treatment when compared with baseline (437% +/- 247% versus
      319% +/- 217%; P = 0.001), but no association was evident between change in
      endothelial function and change in inflammatory markers. CONCLUSIONS: Classical
      CVD risk may influence endothelial function more than disease-related markers of
      inflammation in RA. Classical CVD risk factors and anti-TNF-alpha medication have
      different effects on microvascular and macrovascular endothelial function,
      suggesting that combined CVD-prevention approaches may be necessary. Prospective
      studies examining whether assessments of vascular function are predictive of long
      term CV outcomes in RA are required.

PMID- 22594789
TI  - Color tuning of nanofibers by periodic organic-organic hetero-epitaxy.
AB  - We report on the epitaxial growth of periodic para-hexaphenyl (p-6P)/alpha-sexi
      thiophene (6T) multilayer heterostructures on top of p-6P nanotemplates. By the
      chosen approach, 6T molecules are forced to align parallel to the p-6P template
      molecules, which yields highly polarized photoluminescence (PL)-emission of both
      species. The PL spectra show that the fabricated multilayer structures provide
      optical emission from two different 6T phases, interfacial 6T molecules, and 3
      dimensional crystallites. By a periodical deposition of 6T monolayers and p-6P
      spacers it is demonstrated that the strongly polarized spectral contribution of
      interfacial 6T can be precisely controlled and amplified. By analyzing the PL
      emission of both 6T phases as a function of p-6P spacer thickness (Deltad(p-6P))
      we have determined a critical value of Deltad(p-6P )~ 2.73 nm where interfacial
      6T runs into saturation and the surplus of 6T starts to cluster in 3-dimensional
      crystallites. These results are further substantiated by UPS and XRD
      measurements. Moreover, it is demonstrated by morphological investigations,
      provided by scanning force microscopy and fluorescence microscopy, that
      periodical deposition of 6T and p-6P leads to a significant improvement of
      homogeneity in PL-emission and morphology of nanofibers. Photoluminescence
      excitation experiments in combination with time-resolved photoluminescence
      demonstrate that the spectral emission of the organic multilayer nanofibers is
      dominated by a resonant energy transfer from p-6P host- to 6T guest-molecules.
      The sensitization time of the 6T emission in the 6T/p-6P multilayer structures
      depends on the p-6P spacer thickness, and can be explained by well separated
      layers of host-guest molecules obtained by organic-organic heteroepitaxy. The
      spectral emission and consequently the fluorescent color of the nanofibers can be
      efficiently tuned from the blue via white to the yellow-green spectral range.

PMID- 22594790
TI  - Monitoring of acrylamide concentrations in potato chips in Japan between 2006 and
      2010.
AB  - Acrylamide levels in commercially available potato chips in Japan were monitored
      between August 2006 and June 2010 using the xanthydrol derivative gas
      chromatography-mass spectrometry (GC-MS) method. Seasonal and annual changes in
      acrylamide concentrations were determined. Nationwide bimonthly sampling of
      potato chips was carried out using a four-level design, and seasonal variations
      were detected in which the minimum acrylamide concentration was observed in
      August, and the maximum between February and June. Seasonal variations became
      less apparent after August 2008 as a result of annual effects and/or mitigation
      measures taken by the potato chip producers. Sampling uncertainties were
      separated into time-to-time, city-to-city, and lot-to-lot variation, and the
      largest variation was shown to be lot-to-lot including bag-to-bag.

PMID- 22594791
TI  - A randomized, placebo-controlled study to assess the efficacy of lateral branch
      neurotomy for chronic sacroiliac joint pain: letter to editor.

PMID- 22594793
TI  - Case of intractable ophiasis type of alopecia areata presumably improved by
      fexofenadine.

PMID- 22594792
TI  - Breast cancer suppressor candidate-1 (BCSC-1) is a melanoma tumor suppressor that
      down regulates MITF.
AB  - Understanding the molecular aberrations involved in the development and
      progression of metastatic melanoma (MM) is essential for a better diagnosis and
      targeted therapy. We identified breast cancer suppressor candidate-1 (BCSC-1) as
      a novel tumor suppressor in melanoma. BCSC-1 expression is decreased in human MM,
      and its ectopic expression in MM-derived cell lines blocks tumor formation in
      vivo and melanoma cell proliferation in vitro while increasing cell migration. We
      demonstrate that BCSC-1 binds to Sox10, which down regulates MITF, and results in
      a switch of melanoma cells from a proliferative to a migratory phenotype. In
      conclusion, we have identified BCSC-1 as a tumor suppressor in melanoma and as a
      novel regulator of the MITF pathway.

PMID- 22594794
TI  - Direct meso-alkynylation of porphyrins doubly assisted by pyridyl coordination.
AB  - Direct meso-alkynylation of beta,beta'-dipyridylporphyrin with various
      alkynyllithium reagents has been achieved, in which the beta,beta'-dipyridyl
      groups play an important role in facilitating the nucleophilic addition of the
      reagents through double coordination. This method enabled the synthesis of a meso
      ethynylene-bridged diporphyrin.

PMID- 22594795
TI  - Transcriptome analysis of the duodenum, pancreas, liver, and muscle from diabetic
      Goto-Kakizaki rats fed a trypsin inhibitor derived from squid viscera.
AB  - Trypsin inhibitors (TIs) have various nutritional effects. However, a detailed
      mechanism for their effects, especially on the gene expression patterns in
      various tissues, remains unknown. Here, we used transcriptome techniques and gene
      ontology (GO) analysis to examine the effects of squid TI (sqTI), a biochemically
      stable peptide, on diabetic Goto-Kakizaki rats after feeding for 10 weeks. We
      demonstrated that downregulation of SREBP1c in the liver via duodenal/pancreatic
      hormones suppresses the blood cholesterol level. Consistently, in GO analysis,
      the term "cholesterol biosynthetic process" was enriched among downregulated
      genes. No hypoglycemic or insulinotropic effects were observed, in contrast to
      the results from our previous studies (single stimulation with the same dose of
      TI), which can be partly ascribed to the inactive responses of the duodenum and
      pancreas in this condition.

PMID- 22594796
TI  - Surgical rationalization of living donor liver transplantation by abolition of
      hepatic artery reconstruction under a fixed microscope.
AB  - The small diameter of the hepatic artery is one of the complexities of living
      donor liver transplantation (LDLT). We analyzed whether the direct suture
      technique using surgical loupes can simplify the operative process for LDLT
      compared with fixed microscopic reconstruction. We applied the direct technique
      to rationalize the operative process and abolished routine microsurgery from
      2004. Two hundred and nine LDLT with a postoperative period over 34 months were
      carried out from 1996 to 2008. The patients were divided into two groups: the
      micro group (children: 20, adults: 72) and the non-micro group (children: 12,
      adults: 97). Running anastomosis was undertaken in the non-micro group. The
      anastomotic size of the children was significantly smaller than that of the
      adults, but larger than 2 mm (2.38+/-0.4 vs. 2.7+/-0.47 mm, p=0.0005). By
      appropriate choice of the proximal artery, direct anastomosis is possible even in
      children. Early complications occurred in seven cases in the micro group, but
      none occurred in the non-micro group (p<0.05). Significant reductions were
      observed in operation time (p<0.0001), blood loss (p<0.05), and hospital stay
      (p<0.01) in the non-micro group. Non-microscopic anastomosis is useful for the
      rationalization of LDLT.

PMID- 22594797
TI  - Structural characterization and antimicrobial evaluation of atractyloside,
      atractyligenin, and 15-didehydroatractyligenin methyl ester.
AB  - We report the first complete structure elucidation of the ent-kaurane diterpenoid
      glycoside atractyloside (1) by means of NMR and X-ray diffractometry techniques.
      Extensive one- and two-dimensional NMR experiments were employed to assign the
      proton and carbon signals of 1, and crystallography experiments established the
      configurations of all stereogenic centers. Furthermore, we present a novel
      semisynthetic route for the preparation of the highly cytotoxic aglycone
      derivative of 1, 15-didehydroatractyligenin methyl ester (3). All compounds were
      tested for their antibiotic activity against Enterococcus faecalis, Escherichia
      coli, and several strains of Staphylococcus aureus, including fluoroquinolone
      resistant (SA1199B) and two epidemic MRSA (EMRSA-15 and -16) strains. Compound 3
      exhibited moderate activity against all of the Staph. aureus strains with an MIC
      value of 128 mg/L.

PMID- 22594798
TI  - Subcellular localization and role of Ran1 in Tetrahymena thermophila amitotic
      macronucleus.
AB  - Amitosis, a direct method of cell division is common in ciliated protozoan, fungi
      and some animal and plant cells. During amitosis, intranuclear microtubules are
      reorganized into specified arrays which assist in separation of nucleus, despite
      lack of a bipolar spindle. However, the regulation of amitosis is not understood.
      Here, we focused on the localization and role of mitotic spindle assembly
      regulator: Ran GTPase (Ran1) in macronuclear amitosis in binucleated protozoan
      Tetrahymena thermophila. HA-tagged Ran1 was localized in the macronucleus
      throughout the cell cycle of Tetrahymena during vegetative growth, and the
      accessory factor binding domains of Ran1 contributed to its macronuclear
      localization. Incomplete somatic knockout of RAN1 resulted in aberrant
      intramacronuclear microtubule array formation, missegregation of macronuclear
      chromosomes and ultimately blocked macronuclei proliferation. When the Ran1 cycle
      was perturbed by overexpression of Ran1T25N (GDP-bound Ran1-mimetic) or Ran1Q70L
      (GTP-bound Ran1-mimetic), intramacronuclear microtubule assembly was inhibited or
      multi-micronucleate cells formed. These results suggest that Ran GTPase pathway
      is involved in assembly of a specialized intramacronuclear microtubule network
      and coordinates amitotic progression in Tetrahymena.

PMID- 22594800
TI  - Notch-dependent expression of epithelial-mesenchymal transition markers in
      cholangiocytes after liver transplantation.
AB  - AIM:   Epithelial-mesenchymal transition (EMT) has been identified in chronic
      cholestatic liver diseases, which are characterized by biliary proliferation and
      fibrosis. Activation of Notch signaling mediates EMT in a variety of epithelial
      cell types. In the present study, we investigated the role of Notch signaling in
      the regulation of EMT marker expression in cholangiocytes after liver
      transplantation. METHODS:   Orthotopic liver transplantation was performed in
      Sprague-Dawley rats. Liver tissues and isolated cholangiocytes were collected 1
      week after transplantation. The expression of mesenchymal and biliary epithelial
      markers was evaluated by immunohistochemistry, quantitative polymerase chain
      reaction (PCR) and western blotting in liver sections and isolated
      cholangiocytes. Quantitative real-time PCR and western blotting for Jagged1 and
      HES1 were utilized to evaluate the activation of Notch signaling. Proliferation
      and migration of cholangiocytes were assessed by 5-bromodeoxyuridine and
      transwell assays, respectively. Cholangiocyte proliferation, migration and
      expression of EMT markers were also evaluated following the inhibition of Notch
      signaling with N,(N-[3,5-difluorophenacetyl]-L-alanyl)-S-phenylglycine t
      butylester (gamma-secretase inhibitor) and a Jagged1-neutralizing antibody.
      RESULTS:   Expression of EMT markers by cholangiocytes was observed in liver
      grafts and isolated cholangiocytes obtained 1 week after transplantation.
      Inhibition of Notch signaling prevented the expression of EMT markers in bile
      ducts of liver sections and isolated cholangiocytes. Cholangiocyte proliferative
      and migratory capacities were also suppressed by the inhibition of Notch
      signaling. CONCLUSION:   Activation of Notch signaling promotes cholangiocyte
      proliferation and expression of EMT markers after liver transplantation.

PMID- 22594799
TI  - The human hepatocyte cell lines IHH and HepaRG: models to study glucose, lipid
      and lipoprotein metabolism.
AB  - Metabolic diseases reach epidemic proportions. A better knowledge of the
      associated alterations in the metabolic pathways in the liver is necessary. These
      studies need in vitro human cell models. Several human hepatoma models are used,
      but the response of many metabolic pathways to physiological stimuli is often
      lost. Here, we characterize two human hepatocyte cell lines, IHH and HepaRG, by
      analysing the expression and regulation of genes involved in glucose and lipid
      metabolism. Our results show that the glycolysis pathway is activated by glucose
      and insulin in both lines. Gluconeogenesis gene expression is induced by
      forskolin in IHH cells and inhibited by insulin in both cell lines. The lipogenic
      pathway is regulated by insulin in IHH cells. Finally, both cell lines secrete
      apolipoprotein B-containing lipoproteins, an effect promoted by increasing
      glucose concentrations. These two human cell lines are thus interesting models to
      study the regulation of glucose and lipid metabolism.

PMID- 22594801
TI  - Defects in spliceosomal machinery: a new pathway of leukaemogenesis.
AB  - Proper splicing of pre-mRNA is required for protein synthesis and therefore is a
      fundamental cellular function. The discovery of a variety of somatic spliceosomal
      mutations in haematological malignancies, including myeloid neoplasms and chronic
      lymphocytic leukaemia has pointed to a new leukaemogenic pathway involving
      spliceosomal dysfunction. Theoretically, spliceosomal mutations can lead to
      activation of incorrect splice sites, intron retention or aberrant alternative
      splicing occurring in patterns generated by mutations of individual spliceosomal
      proteins. Such events can produce a defective balance between protein isoforms
      leading to functional consequences including defective regulation of
      proliferation and differentiation. The observed pattern of occurrence of highly
      specific missense mutations, coupled with the lack of nonsense mutations and
      deletions, implies a gain-of-function or better gain-of-dysfunction mechanism.
      Incorrect splicing of downstream genes, such as tumour suppressor genes, may
      result in haploinsufficient expression through nonsense-mediated mRNA decay.
      Thus, spliceosomal mutations may, depending on the pattern of affected proteins,
      lead to similar functional effects on tumour suppressor genes as chromosomal
      deletions, epigenetic silencing or inactivating/hypomorphic mutations. The
      prognostic value of the most common mutations and their phenotypic association in
      the clinical setting is currently under investigation. It is likely that
      spliceosomal mutations may indicate sensitivity to spliceosome inhibitors applied
      in the form of a synthetic lethal approach. This review discusses the most
      current aspects of spliceosomal research in the context of haematological
      malignancies.

PMID- 22594802
TI  - Multiphase chemical kinetics of the nitration of aerosolized protein by ozone and
      nitrogen dioxide.
AB  - Proteins contained in pollen and other biological particles are nitrated by ozone
      and nitrogen dioxide in polluted air. The nitration can enhance the allergenic
      potential of proteins, which may contribute to the increasing prevalence of
      allergic diseases. The reactive uptake of NO(2) by aerosolized protein (bovine
      serum albumin) was investigated in an aerosol flow tube using the short-lived
      radioactive tracer (13)N. In the absence of O(3), the NO(2) uptake coefficient
      was below detection limit (gamma(NO2) < 10(-6)), but with 20-160 ppb O(3)
      gamma(NO2) increased from ~10(-6) to ~10(-4). Using the kinetic multilayer model
      of surface and bulk chemistry (KM-SUB), the observed time and concentration
      dependence can be well reproduced by a multiphase chemical mechanism involving
      ozone-generated reactive oxygen intermediates (ROIs), but not by NO(3) radicals
      formed in the gas phase. Product studies show the formation of protein dimers,
      suggesting that the ROIs are phenoxy radical derivatives of the amino acid
      tyrosine (tyrosyl radicals) which are also involved in physiological protein
      nitration processes. Our results imply that proteins on the surface of aerosol
      particles undergo rapid nitration in polluted air, while the rate of nitration in
      bulk material may be low depending on phase state and surface-to-volume ratio.

PMID- 22594803
TI  - Reliable and rapid characterization of functional FCN2 gene variants reveals
      diverse geographical patterns.
AB  - BACKGROUND: Ficolin-2 coded by FCN2 gene is a soluble serum protein and an innate
      immune recognition element of the complement system. FCN2 gene polymorphisms
      reveal distinct geographical patterns and are documented to alter serum ficolin
      levels and modulate disease susceptibility. METHODS: We employed a real-time PCR
      based on Fluorescence Resonance Energy Transfer (FRET) method to genotype four
      functional SNPs including -986 G > A (#rs3124952), -602 G > A (#rs3124953), -4A >
      G (#rs17514136) and +6424 G > T (#rs7851696) in the ficolin-2 (FCN2) gene. We
      characterized the FCN2 variants in individuals representing Brazilian (n = 176),
      Nigerian (n = 180), Vietnamese (n = 172) and European Caucasian ethnicity (n =
      165). RESULTS: We observed that the genotype distribution of three functional SNP
      variants (-986 G > A, -602 G > A and -4A > G) differ significantly between the
      populations investigated (p < 0.0001). The SNP variants were highly linked to
      each other and revealed significant population patterns. Also the distribution of
      haplotypes revealed distinct geographical patterns (p < 0.0001). CONCLUSIONS: The
      observed distribution of the FCN2 functional SNP variants may likely contribute
      to altered serum ficolin levels and this may depend on the different disease
      settings in world populations. To conclude, the use of FRET based real-time PCR
      especially for FCN2 gene will benefit a larger scientific community who
      extensively depend on rapid, reliable method for FCN2 genotyping.

PMID- 22594804
TI  - Allergic contact dermatitis induces upregulation of identical microRNAs in humans
      and mice.
AB  - BACKGROUND: MicroRNAs are short, endogenous RNA molecules that can bind to parts
      of target mRNAs, thus inhibiting their translation and causing accelerated
      turnover or degradation of transcripts, thereby regulating gene expression.
      Several microRNAs have been found to be upregulated in atopic dermatitis and
      psoriasis, indicating a role in inflammatory skin diseases. However, there have
      been no studies on the expression of microRNAs in allergic contact dermatitis.
      OBJECTIVES: To investigate expression of microRNAs in allergic contact
      dermatitis. Methods. Lesional and non-lesional skin biopsies were collected from
      subjects with allergic responses to diphenylcyclopropenone (DPCP). Additional
      samples for profiling were collected from an experimental mouse model by use of
      the strong allergen dinitrofluorobenzene. RNA was purified from all samples, and
      locked nucleic acid microarray analysis was performed, followed by validation
      with quantitative polymerase chain reaction (PCR). RESULTS: In humans sensitized
      with DPCP, we found significant upregulation of miR-21, miR-142-3p, miR-142-5p
      and miR-223 in challenged skin. The same microRNAs were significantly upregulated
      in the skin of mice in a mouse model of contact allergy. The upregulation of
      microRNA was confirmed by quantitative PCR. CONCLUSION: These are the first
      results indicating that microRNAs may be involved in the pathogenesis of allergic
      contact dermatitis, and they show that mouse models are valuable tools for
      further study of the involvement of microRNAs in allergic contact dermatitis.

PMID- 22594805
TI  - Effects of controlled-release formulations of atypical antipsychotics on
      functioning and quality of life of schizophrenic individuals.
AB  - INTRODUCTION: Controlled-release formulations of atypical antipsychotics have
      recently been introduced into clinical practice. Clinical studies have indicated
      that these new therapies induce meaningful improvements in the functioning and
      quality of life of schizophrenic individuals. AREAS COVERED: The present analysis
      makes an attempt to address the clinical relevance of these studies and their
      contribution to the understanding of the mechanisms of action of these new drugs.
      A Medline search was done using the keywords 'antipsychotic', 'plasma level',
      'quality of life' and 'functioning'. EXPERT OPINION: After reviewing the
      literature, it seems that symptom control and side effects may play a role in
      modulating the functioning and quality of life of schizophrenic individuals
      treated with controlled-release formulations of atypical antipsychotics. The
      analysis also highlights that these new drugs may possess peculiarities and
      similarities in regulating patient functioning. However, the low number of
      clinical analyses that have focused on these aspects of antipsychotic therapy
      limits the interpretation of the results. Additional comparative clinical trials
      are needed to evaluate how the pharmacokinetic/pharmacodynamic properties of
      antipsychotic drugs may modulate the functioning and quality of life of
      schizophrenic individuals, as well as to establish whether new clinical benefits
      may come from the use of these drugs in schizophrenia therapy.

PMID- 22594807
TI  - Comments on efficacy of radiofrequency facet denervation procedures.

PMID- 22594806
TI  - Association between a genetic variant in the serotonin transporter gene (SLC6A4)
      and suicidal behavior in patients with schizophrenia.
AB  - BACKGROUND: The serotonin (5-hydroxytryptamin; 5-HT) system has a central role in
      the circuitry of cognition and emotions. Multiple lines of evidence suggest that
      genetic variation in the serotonin transporter gene (SLC6A4; 5-HTT) is associated
      with schizophrenia and suicidal behavior. In this study, we wanted to elucidate
      whether SLC6A4 variations is involved in attempted suicide among patients with
      schizophrenia in a Scandinavian case-control sample. METHODS: Patients diagnosed
      with schizophrenia from three Scandinavian samples were assessed for presence or
      absence of suicide attempts, based on record reviews and interview data. Seven
      SLC6A4 single nucleotide polymorphisms (SNPs) were genotyped in 837 schizophrenia
      patients and 1,473 control individuals. Association analyses and statistical
      evaluations were performed with the program UNPHASED (version 3.0.9). RESULTS: We
      observed an allele association between the SNP rs16965628, located in intron one
      of SLC6A4, and attempted suicide (adjusted p-value 0.01), among patients with
      schizophrenia. No association was found to a diagnosis of schizophrenia, when
      patients were compared to healthy control individuals. CONCLUSION: The gene
      SLC6A4 appears to be involved in suicidal ideation among patients with
      schizophrenia. Independent replication is needed before more firm conclusions can
      be drawn.

PMID- 22594808
TI  - High-resolution resistless nanopatterning on polymer and flexible substrates for
      plasmonic biosensing using stencil masks.
AB  - The development of nanoscale lithographic methods on polymer materials is a key
      requirement to improve the spatial resolution and performance of flexible
      devices. Here, we report the fabrication of metallic nanostructures down to 20
      and 50 nm in size on polymer materials such as polyimide, parylene, SU-8, and
      PDMS substrates without any resist processing using stencil lithography. Metallic
      nanodot array analysis of their localized surface plasmon spectra is included. We
      demonstrate plasmon resonance detection of biotin and streptavidin using a PDMS
      flexible film with gold nanodots. We also demonstrate the fabrication of metallic
      nanowires on polyimide substrates with their electrical characteristics showing
      an ohmic behavior. These results demonstrate high-resolution nanopatterning and
      device nanofabrication capability of stencil lithography on polymer and flexible
      substrates.

PMID- 22594809
TI  - Prevalence of retinitis pigmentosa in India: the Central India Eye and Medical
      Study.

PMID- 22594810
TI  - Response format, magnitude of laterality effects, and sex differences in
      laterality.
AB  - The present study examined the evidence for the claim that response format might
      affect the magnitude of laterality effects by means of a meta-analysis. The
      analysis included the 396 effect sizes drawn from 266 studies retrieved by Voyer
      (1996) and relevant to the main effect of laterality and sex differences in
      laterality for verbal and non-verbal tasks in the auditory, tactile, and visual
      sensory modality. The response format used in specific studies was the only
      moderator variable of interest in the present analysis, resulting in four broad
      response categories (oral, written, computer, and pointing). A meta-analysis
      analogue to ANOVA showed no significant influence of response format on either
      the main effect of laterality or sex differences in laterality when all sensory
      modalities were combined. However, when modalities were considered separately,
      response format affected the main effect of laterality in the visual modality,
      with a clear advantage for written responses. Further pointed analyses revealed
      some specific differences among response formats. Results are discussed in terms
      of their implications for the measurement of laterality.

PMID- 22594811
TI  - Handedness is modulated by sex and self-perception.
AB  - The distribution of handedness is different for men and women. Less pronounced
      right- or left-handedness in men is well established and often attributed to
      direct effects of genetic factors. Many studies observing this sex difference
      assessed handedness via questionnaire. It may therefore be influenced by a sex
      specific bias in self-perception. Permanent inadequate self-perceptions are key
      characteristics of hypochondriasis. The study therefore tested 1017 participants
      (614 females) on two standard questionnaires to assess handedness and
      hypochondriasis: the Edinburgh Inventory and the Whiteley Index. Effects of sex,
      hypochondriac traits and the direction of handedness (left-handers; right
      handers) on the degree of handedness (DH; the strength of lateralisation) were
      tested with multivariate linear regression. In confirmation of previous results,
      the DH is lower (less pronounced) in right-handed males than right-handed
      females, but is similar across sexes in left-handers. Regression analyses showed
      that for right-handers, male sex and higher hypochondriac traits are independent
      predictors of lower DH. For left-handers, main effects of sex and hypochondriac
      traits are not significant whereas a significant interaction of these two factors
      indicates that in left-handed men higher hypochondriac traits are associated with
      a differentially stronger shift towards lower DH compared to left-handed women.
      In conclusion, the DH is modulated by sex-specific effects of self-perception for
      left-handers but not right-handers. The implications of this finding on current
      theories of the inheritance of handedness are discussed. The assessment of
      hypochondriac traits might be useful to control response bias in questionnaire
      based studies of human handedness.

PMID- 22594812
TI  - Auditory evoked potentials of adults who do or do not show a significant right
      ear advantage in dichotic listening.
AB  - The Halwes Fused Dichotic Words Test was used to divide a sample of university
      students into a group having a statistically significant right ear advantage
      (REA) and a group having either a significant left ear advantage or a non
      significant ear asymmetry (NREA). Of these participants, 30 (14 REA, 16 NREA) had
      electrical potentials measured from temporal, central, and frontal sites as
      series of brief tones were presented monaurally. No behavioural response was
      required. Group differences were found in the latency but not the amplitude of
      the averaged event-related responses. The REA group showed faster conduction to
      the right hemisphere than to the left hemisphere. In both groups the amplitude of
      left hemisphere responses was greater for right ear stimulation than for left ear
      stimulation. The results for amplitude indicate that the crossed auditory pathway
      is a superior conductor of information to the left hemisphere but not to the
      right hemisphere. Group differences, however, are related only to the speed with
      which information reaches the right hemisphere.

PMID- 22594813
TI  - Inconsistent vs consistent right-handers' performance on an episodic memory task:
      evidence from the California Verbal Learning Test.
AB  - Inconsistent handedness is associated with better memory performance on episodic
      memory tasks than consistent handedness. The present study further explored this
      difference in memory related to handedness by administering a measure that is
      used in clinical settings to assess different aspects of long-term memory. The
      results indicated that inconsistent right-handed individuals recalled and
      recognised more words on the California Verbal Learning Test-II than consistent
      right-handed individuals. Inconsistent right-handers also showed better
      performance than consistent right-handers on measures of source recognition. The
      results of this study further extend the effects of handedness on memory to the
      clinical setting because the CVLT-II is a measure used extensively in clinical
      neuropsychology.

PMID- 22594814
TI  - Left-handedness is statistically linked to lifetime experimentation with illicit
      drugs.
AB  - Handedness has been linked to an enhanced risk of alcohol abuse, while less is
      known about other drugs. A convenience sample of 1004 male and female Italian
      participants (females=58%) from the general community (18 to 65 years old:
      average age = 30; standard deviation = 10, median = 25) was asked about:
      handedness (preference in writing); lifetime use of alcohol, tobacco, and illicit
      drugs; levels of psychological distress, as measured by the General Health
      Questionnaire (GHQ); and levels of delusion proneness, as measured by the Peters
      et al. Delusions Inventory (PDI). Overall, 92 individuals (9.2%) were classified
      as left-handed, with no significant difference reported among genders. Lifetime
      use of illicit drugs, primarily cannabis, was reported by 20% of the sample. In a
      multiple logistic regression analysis, after taking into account sex, age, and
      caseness on GHQ and PDI, left-handed people in the sample were statistically more
      likely to report lifetime experimentation with heroin, ecstasy/amphetamine, and,
      marginally, hallucinogens, but not alcohol or tobacco. Different mechanisms might
      contribute to an explanation of greater lifetime experimentation with some
      illicit drugs among left-handed people as compared to right-handed people.
      However, replications with clinical samples are necessary before any definitive
      statements can be made.

PMID- 22594816
TI  - Breastfeeding predicts handedness.
AB  - This study examined whether being breastfed predicts handedness. Two large
      representative samples from Britain (n=13,421) and Ireland (n=8,426) were used.
      Multivariate probit models are estimated, reporting the marginal effects of
      covariates on the probability of a child being right-handed. For both datasets,
      children who have been breastfed for a minimum period (between 1 month and 6
      weeks) are significantly less likely to be left-handed. The results are robust to
      a variety of controls. Hence breastfeeding is an environmental factor that
      predicts handedness in a non-linear way, although the mechanism is unknown.

PMID- 22594815
TI  - A demonstration that task difficulty can confound the interpretation of lateral
      differences in brain activation between typical and dyslexic readers.
AB  - Dyslexic readers (DRs) manifest atypical patterns of brain activity, which may be
      attributed to aberrant neural connectivity and/or an attempt to activate
      compensatory pathways. This paper evaluates whether differences in brain
      activation patterns between DRs and typical readers (TRs) are confounded by task
      difficulty. Eight DRs and eight TRs matched for age, sex, and nonverbal IQ
      performed pseudoword rhyming tasks at two levels of difficulty during
      magnetoencephalography. Task difficulty varied with the number of successive
      target pseudowords presented before the test pseudoword. Regions of interest
      were: the temporoparietal area (TPA), the ventral occipital temporal area (VOT),
      and the inferior frontal gyrus (IFG). Activity was analysed for the 660-ms period
      after test pseudoword onset. During the discrepant performance condition left
      hemispheric TPA activation increased across time for TRs, but not DRs, and IFG
      bihemispheric activation was greater in TRs by the end of the trial. During the
      equivalent performance condition no group differences in TPA or IFG activation
      were found. We argue that these results indicate that direct comparison of DR
      versus TR brain activity is confounded when DRs are more challenged than TRs.
      This highlights the importance of equating reading group performance during
      neuroimaging of reading-related tasks.

PMID- 22594817
TI  - Hemispheric resource availability influences face perception: a multiple resource
      approach to social perception.
AB  - Two experiments tested the hypothesis that social perception recruits distinct
      limited-capacity processing resources that are distinguished by the cerebral
      hemispheres. To test this hypothesis, social perception efficiency was assessed
      after relevant hemispheric processing resources were depleted. In Experiment 1
      prime faces were unilaterally presented for 30 ms, after which centrally
      presented target faces were categorised by sex. In Experiment 2 prime faces were
      unilaterally presented for 80 ms after which centrally presented target faces
      were categorised by fame. Results showed that sex categorisation was slower after
      primes were presented in the right versus left visual field, and that fame
      categorisation was slower after familiar primes were presented in the left versus
      right visual field. The results support a multiple resource account of social
      perception in which the availability of resources distributed across the cerebral
      hemispheres influences social perception.

PMID- 22594820
TI  - Discovery of an S-equol rich food stinky tofu, a traditional fermented soy
      product in Taiwan.
AB  - A recent epidemiological study showed that daily intake of mg quantities of S
      equol is required for health-promoting effects in menopausal women. However, the
      maximum equol content in food was reported to be approximately 130 MUg/100 g in
      egg yolk. The objective of this study was to find a high equol-containing food.
      We measured the equol content of 33 egg yolks and 21 fermented soybean foods.
      Equol was detected in 28 egg yolks at the maximum content of 43 MUg/100 g. In the
      fermented soybean foods, equol was detected only in stinky tofu. We examined 16
      stinky tofu samples purchased during different seasons and the average equol
      content was 1.39 mg/100 g, ranging from 0.34 to 2.68 mg/100 g. Equol was present
      in stinky tofu as the S-enantiomeric form and as an aglycon type. This is the
      first report demonstrating that stinky tofu contains high levels of S-equol,
      which may exert beneficial effects in menopausal women.

PMID- 22594822
TI  - Magneto-optical enhancement by plasmon excitations in nanoparticle/metal
      structures.
AB  - Coupling magnetic materials to plasmonic structures provides a pathway to
      dramatically increase the magneto-optical response of the resulting composite
      architecture. Although such optical enhancement has been demonstrated in a
      variety of systems, some basic aspects are scarcely known. In particular,
      reflectance/transmission modulations and electromagnetic field intensification,
      both triggered by plasmon excitations, can contribute to the magneto-optical
      enhancement. However, a quantitative evaluation of the impact of both factors on
      the magneto-optical response is lacking. To address this issue, we have measured
      magneto-optical Kerr spectra on corrugated gold/dielectric interfaces with
      magnetic (nickel and iron oxide) nanoparticles. We find that the magneto-optical
      activity is enhanced by up to an order of magnitude for wavelengths that are
      correlated to the excitation of propagating or localized surface plasmons. Our
      work sheds light on the fundamental principles for the observed optical response
      and demonstrates that the outstanding magneto-optical performance is originated
      by the increase of the polarization conversion efficiency, whereas the
      contribution of reflectance modulations is negligible.

PMID- 22594821
TI  - T-cell autoreactivity to citrullinated autoantigenic peptides in rheumatoid
      arthritis patients carrying HLA-DRB1 shared epitope alleles.
AB  - INTRODUCTION: Anti-citrullinated peptide antibodies are found in rheumatoid
      arthritis (RA) patients with HLA-DRbeta chains encoding the shared epitope (SE)
      sequence. Citrullination increases self-antigen immunogenicity, through increased
      binding affinity to SE-containing HLA-DR molecules. To characterise T-cell
      autoreactivity towards citrullinated self-epitopes, we profiled responses of SE+
      healthy controls and RA patients to citrullinated and unmodified epitopes of four
      autoantigens. METHODS: We compared T-cell proliferative and cytokine responses to
      citrullinated and native type II collagen 1,237 to 1,249, vimentin 66 to 78,
      aggrecan 84 to 103 and fibrinogen 79 to 91 in six SE+ healthy controls and in 21
      RA patients with varying disease duration. Cytokine-producing cells were stained
      after incubation with peptide in the presence of Brefeldin-A. RESULTS: Although
      proliferative responses were low, IL-6, IL-17 and TNF were secreted by CD4+ T
      cells of SE+ RA patients and healthy controls, as well as IFNgamma and IL-10
      secreted by RA patients, in response to citrullinated peptides. Of the epitopes
      tested, citrullinated aggrecan was most immunogenic. Patients with early RA were
      more likely to produce IL-6 in response to no epitope or to citrullinated
      aggrecan, while patients with longstanding RA were more likely to produce IL-6 to
      more than one epitope. Cytokine-producing CD4+ T cells included the CD45RO+ and
      CD45RO- and the CD28+ and CD28- subsets in RA patients. CONCLUSION:
      Proinflammatory cytokines were produced by CD4+ T cells in SE+ individuals in
      response to citrullinated self-epitopes, of which citrullinated aggrecan was most
      immunogenic. Our data suggest that the T-cell response to citrullinated self
      epitopes matures and diversifies with development of RA.

PMID- 22594823
TI  - Hyalinized fibrosis-predominant fibrolipoma of the back.

PMID- 22594824
TI  - Vegetal polymer in repair of defects of the orbital floor: an experimental study
      in rabbits.
AB  - BACKGROUND: An experimental study was done to assess the ability of the vegetal
      polymer miniplates and screws to repair defects of the orbital floor. METHODS: An
      artificial standard-sized defect was created in the bony floor of right orbit of
      45 albino rabbits. The animals were divided into three experimental groups:
      control group (G1) involving animals with orbital floor defect and no treatment;
      titanium group (G2) containing animals with orbital floor defect repaired by
      titanium miniplates and screws; vegetal polymer group (G3) composed of animals
      with similar orbital floor defects repaired by vegetal polymer miniplates and
      screws. Throughout the course of the experiment, the animals were clinically
      evaluated. At 15, 30 and 60 days after surgery, the animals were killed. They
      were X-rayed immediately after the floor defect and at the moment of sacrifice.
      Histological and morphometric evaluation of inflammatory reaction and bone
      healing was done. Data were statistically evaluated. RESULTS: No implants were
      extruded. Bone consolidation was similar in G2 and G3 and better than in G1 group
      animals. Inflammatory reaction was most pronounced in animals of G3 15 days after
      surgery, and it subsided over time. CONCLUSION: Vegetal polymer miniplates and
      screws induces small inflammatory reaction and had the ability to stimulate bone
      growth with good integration in the orbital floor defect allowing to consider the
      vegetal polymer adequate option to treat orbital floor defects. Future studies
      involving long-term follow-up and biomechanical tests to evaluate material
      resistance to traction are needed.

PMID- 22594825
TI  - Exploring the sequence-function relationship in transcriptional regulation by the
      lac O1 operator.
AB  - Understanding how binding of a transcription factor to an operator is influenced
      by the operator sequence is an ongoing quest. It facilitates discovery of
      alternative binding sites as well as tuning of transcriptional regulation. We
      investigated the behavior of the Escherichia coli Lac repressor (LacI) protein
      with a large set of lac O(1) operator variants. The 114 variants examined
      contained a mean of 2.9 (range 0-4) mutations at positions -4, -2, +2 and +4 in
      the minimally required 17 bp operator. The relative affinity of LacI for the
      operators was examined by quantifying expression of a GFP reporter gene and
      Rosetta structural modeling. The combinations of mutations in the operator
      sequence created a wide range of regulatory behaviors. We observed variations in
      the GFP fluorescent signal among the operator variants of more than an order of
      magnitude under both uninduced and induced conditions. We found that a single
      nucleotide change may result in changes of up to six- and 12-fold in uninduced
      and induced GFP signals, respectively. Among the four positions mutated, we found
      that nucleotide G at position -4 is strongly correlated with strong repression.
      By Rosetta modeling, we found a significant correlation between the calculated
      binding energy and the experimentally observed transcriptional repression
      strength for many operators. However, exceptions were also observed, underscoring
      the necessity for further improvement in biophysical models of protein-DNA
      interactions.

PMID- 22594827
TI  - Distinguishing the causes of firing with the membrane potential slope.
AB  - In this letter, we aim to measure the relative contribution of coincidence
      detection and temporal integration to the firing of spikes of a simple neuron
      model. To this end, we develop a method to infer the degree of synchrony in an
      ensemble of neurons whose firing drives a single postsynaptic cell. This is
      accomplished by studying the effects of synchronous inputs on the membrane
      potential slope of the neuron and estimating the degree of response-relevant
      input synchrony, which determines the neuron's operational mode. The measure is
      calculated using the normalized slope of the membrane potential prior to the
      spikes fired by a neuron, and we demonstrate that it is able to distinguish
      between the two operational modes. By applying this measure to the membrane
      potential time course of a leaky integrate-and-fire neuron with the partial
      somatic reset mechanism, which has been shown to be the most likely candidate to
      reflect the mechanism used in the brain for reproducing the highly irregular
      firing at high rates, we show that the partial reset model operates as a temporal
      integrator of incoming excitatory postsynaptic potentials and that coincidence
      detection is not necessary for producing such high irregular firing.

PMID- 22594828
TI  - Nearly extensive sequential memory lifetime achieved by coupled nonlinear
      neurons.
AB  - Many cognitive processes rely on the ability of the brain to hold sequences of
      events in short-term memory. Recent studies have revealed that such memory can be
      read out from the transient dynamics of a network of neurons. However, the memory
      performance of such a network in buffering past information has been rigorously
      estimated only in networks of linear neurons. When signal gain is kept low, so
      that neurons operate primarily in the linear part of their response nonlinearity,
      the memory lifetime is bounded by the square root of the network size. In this
      work, I demonstrate that it is possible to achieve a memory lifetime almost
      proportional to the network size, "an extensive memory lifetime," when the
      nonlinearity of neurons is appropriately used. The analysis of neural activity
      revealed that nonlinear dynamics prevented the accumulation of noise by partially
      removing noise in each time step. With this error-correcting mechanism, I
      demonstrate that a memory lifetime of order N/logN can be achieved.

PMID- 22594829
TI  - Inhibition in multiclass classification.
AB  - The role of inhibition is investigated in a multiclass support vector machine
      formalism inspired by the brain structure of insects. The so-called mushroom
      bodies have a set of output neurons, or classification functions, that compete
      with each other to encode a particular input. Strongly active output neurons
      depress or inhibit the remaining outputs without knowing which is correct or
      incorrect. Accordingly, we propose to use a classification function that embodies
      unselective inhibition and train it in the large margin classifier framework.
      Inhibition leads to more robust classifiers in the sense that they perform better
      on larger areas of appropriate hyperparameters when assessed with leave-one-out
      strategies. We also show that the classifier with inhibition is a tight bound to
      probabilistic exponential models and is Bayes consistent for 3-class problems.
      These properties make this approach useful for data sets with a limited number of
      labeled examples. For larger data sets, there is no significant comparative
      advantage to other multiclass SVM approaches.

PMID- 22594830
TI  - Hebbian learning of recurrent connections: a geometrical perspective.
AB  - We show how a Hopfield network with modifiable recurrent connections undergoing
      slow Hebbian learning can extract the underlying geometry of an input space.
      First, we use a slow and fast analysis to derive an averaged system whose
      dynamics derives from an energy function and therefore always converges to
      equilibrium points. The equilibria reflect the correlation structure of the
      inputs, a global object extracted through local recurrent interactions only.
      Second, we use numerical methods to illustrate how learning extracts the hidden
      geometrical structure of the inputs. Indeed, multidimensional scaling methods
      make it possible to project the final connectivity matrix onto a Euclidean
      distance matrix in a high-dimensional space, with the neurons labeled by spatial
      position within this space. The resulting network structure turns out to be
      roughly convolutional. The residual of the projection defines the
      nonconvolutional part of the connectivity, which is minimized in the process.
      Finally, we show how restricting the dimension of the space where the neurons
      live gives rise to patterns similar to cortical maps. We motivate this using an
      energy efficiency argument based on wire length minimization. Finally, we show
      how this approach leads to the emergence of ocular dominance or orientation
      columns in primary visual cortex via the self-organization of recurrent rather
      than feedforward connections. In addition, we establish that the nonconvolutional
      (or long-range) connectivity is patchy and is co-aligned in the case of
      orientation learning.

PMID- 22594831
TI  - Multilabel classification with principal label space transformation.
AB  - We consider a hypercube view to perceive the label space of multilabel
      classification problems geometrically. The view allows us not only to unify many
      existing multilabel classification approaches but also design a novel algorithm,
      principal label space transformation (PLST), that captures key correlations
      between labels before learning. The simple and efficient PLST relies on only
      singular value decomposition as the key step. We derive the theoretical guarantee
      of PLST and evaluate its empirical performance using real-world data sets.
      Experimental results demonstrate that PLST is faster than the traditional binary
      relevance approach and is superior to the modern compressive sensing approach in
      terms of both accuracy and efficiency.

PMID- 22594832
TI  - Learning the dynamics of objects by optimal functional interpolation.
AB  - Many areas of science and engineering rely on functional data and their numerical
      analysis. The need to analyze time-varying functional data raises the general
      problem of interpolation, that is, how to learn a smooth time evolution from a
      finite number of observations. Here, we introduce optimal functional
      interpolation (OFI), a numerical algorithm that interpolates functional data over
      time. Unlike the usual interpolation or learning algorithms, the OFI algorithm
      obeys the continuity equation, which describes the transport of some types of
      conserved quantities, and its implementation shows smooth, continuous flows of
      quantities. Without the need to take into account equations of motion such as the
      Navier-Stokes equation or the diffusion equation, OFI is capable of learning the
      dynamics of objects such as those represented by mass, image intensity, particle
      concentration, heat, spectral density, and probability density.

PMID- 22594833
TI  - Optimal population codes for space: grid cells outperform place cells.
AB  - Rodents use two distinct neuronal coordinate systems to estimate their position:
      place fields in the hippocampus and grid fields in the entorhinal cortex. Whereas
      place cells spike at only one particular spatial location, grid cells fire at
      multiple sites that correspond to the points of an imaginary hexagonal lattice.
      We study how to best construct place and grid codes, taking the probabilistic
      nature of neural spiking into account. Which spatial encoding properties of
      individual neurons confer the highest resolution when decoding the animal's
      position from the neuronal population response? A priori, estimating a spatial
      position from a grid code could be ambiguous, as regular periodic lattices
      possess translational symmetry. The solution to this problem requires lattices
      for grid cells with different spacings; the spatial resolution crucially depends
      on choosing the right ratios of these spacings across the population. We compute
      the expected error in estimating the position in both the asymptotic limit, using
      Fisher information, and for low spike counts, using maximum likelihood
      estimation. Achieving high spatial resolution and covering a large range of space
      in a grid code leads to a trade-off: the best grid code for spatial resolution is
      built of nested modules with different spatial periods, one inside the other,
      whereas maximizing the spatial range requires distinct spatial periods that are
      pairwisely incommensurate. Optimizing the spatial resolution predicts two grid
      cell properties that have been experimentally observed. First, short lattice
      spacings should outnumber long lattice spacings. Second, the grid code should be
      self-similar across different lattice spacings, so that the grid field always
      covers a fixed fraction of the lattice period. If these conditions are satisfied
      and the spatial "tuning curves" for each neuron span the same range of firing
      rates, then the resolution of the grid code easily exceeds that of the best
      possible place code with the same number of neurons.

PMID- 22594834
TI  - Father for the first time--development and validation of a questionnaire to
      assess fathers' experiences of first childbirth (FTFQ).
AB  - BACKGROUND: A father's experience of the birth of his first child is important
      not only for his birth-giving partner but also for the father himself, his
      relationship with the mother and the newborn. No validated questionnaire
      assessing first-time fathers' experiences during childbirth is currently
      available. Hence, the aim of this study was to develop and validate an instrument
      to assess first-time fathers' experiences of childbirth. METHOD: Domains and
      items were initially derived from interviews with first-time fathers, and
      supplemented by a literature search and a focus group interview with midwives.
      The comprehensibility, comprehension and relevance of the items were evaluated by
      four paternity research experts and a preliminary questionnaire was pilot tested
      in eight first-time fathers. A revised questionnaire was completed by 200 first
      time fathers (response rate = 81%) Exploratory factor analysis using principal
      component analysis with varimax rotation was performed and multitrait scaling
      analysis was used to test scaling assumptions. External validity was assessed by
      means of known-groups analysis. RESULTS: Factor analysis yielded four factors
      comprising 22 items and accounting 48% of the variance. The domains found were
      Worry, Information, Emotional support and Acceptance. Multitrait analysis
      confirmed the convergent and discriminant validity of the domains; however,
      Cronbach's alpha did not meet conventional reliability standards in two domains.
      The questionnaire was sensitive to differences between groups of fathers
      hypothesized to differ on important socio demographic or clinical variables.
      CONCLUSIONS: The questionnaire adequately measures important dimensions of first
      time fathers' childbirth experience and may be used to assess aspects of fathers'
      experiences during childbirth. To obtain the FTFQ and permission for its use,
      please contact the corresponding author.

PMID- 22594835
TI  - Synthesis of nitrogen-bridged terthiophenes by tandem Buchwald-Hartwig coupling
      and their properties.
AB  - The first synthesis of nitrogen-bridged terthiophenes (NBTTs) has been achieved
      by a tandem Buchwald-Hartwig coupling of 3,3',3",4'-tetrabromo-2,2':5',2"
      terthiophene. Several NBTT derivatives bearing aryl or alkyl moieties on the N
      atoms could be synthesized. Their fundamental electrochemical characteristics and
      HOMO-LUMO levels were found to be influenced by the substituents on the N-atoms.

PMID- 22594837
TI  - Unexpected absorbance enhancement upon clustering dyes in a polymer matrix.
AB  - PE films grafted with poly(methyl acrylate) and labeled with pyrene groups were
      obtained by irradiation with gamma-rays in the presence of acryloyl chloride and
      further reacting them with 1-pyrenebutanol or 1-pyrenemethylamine.
      Characterization of the polymer films benefited from the dual use of the pyrene
      probe as an indicator of, first, polymer chain dynamics by monitoring pyrene
      excimer formation by fluorescence and, second, polymer morphology by staining the
      pyrene-rich domains of the films with RuO(4) for scanning electron microscopy
      (SEM). The grafted polymers labeled with 1-pyrenemethylamine showed much stronger
      absorbance than those labeled with 1-pyrenebutanol despite having similar pyrene
      contents. The fluorescence spectra of the grafted polymers labeled with 1
      pyrenebutanol exhibited monomer emission, whereas those labeled with 1
      pyrenemethylamine exhibited exclusively excimer emission. These dramatic
      differences could be accounted for by noting that labeling of the grafted
      poly(acryloyl chloride) with 1-pyrenemethylamine results in cross-linking of the
      polymer matrix, with an associated enhancement of the concentration of pyrene in
      the cross-linked domains, which was confirmed by SEM. Formation of discrete
      domains in the polymer film can induce multiple scattering at the domain
      boundaries which lengthens the path of light in the film and increases absorption
      of the light by the tightly packed pyrene-rich domains. Implementation of this
      effect for  fabrication of plastic color filters should generate more efficient
      filters which should find numerous practical applications.

PMID- 22594836
TI  - Computational molecular phenotyping of retinal sheet transplants to rats with
      retinal degeneration.
AB  - Retinal progenitor sheet transplants have been shown to extend neuronal processes
      into a degenerating host retina and to restore visual responses in the brain. The
      aim of this study was to identify cells involved in transplant signals to retinal
      degenerate hosts using computational molecular phenotyping (CMP). S334ter line 3
      rats received fetal retinal sheet transplants at the age of 24-40 days. Donor
      tissues were incubated with slow-releasing microspheres containing brain-derived
      neurotrophic factor or glial cell-derived neurotrophic factor. Up to 265 days
      after surgery, eyes of selected rats were vibratome-sectioned through the
      transplant area (some slices stained for donor marker human placental alkaline
      phosphatase), dehydrated and embedded in Eponate, sectioned into serial ultrathin
      datasets and probed for rhodopsin, cone opsin, CRALBP (cellular retinaldehyde
      binding protein), l-glutamate, l-glutamine, glutathione, glycine, taurine, gamma
      aminobutyric acid (GABA) and DAPI (4',6-diamidino-2-phenylindole). In large
      transplant areas, photoreceptor outer segments in contact with host retinal
      pigment epithelium revealed rod and cone opsin immunoreactivity whereas no such
      staining was found in the degenerate host retina. Transplant photoreceptor layers
      contained high taurine levels. Glutamate levels in the transplants were higher
      than in the host retina whereas GABA levels were similar. The transplant inner
      nuclear layer showed some loss of neurons, but amacrine cells and horizontal
      cells were not reduced. In many areas, glial hypertrophy between the host and
      transplant was absent and host and transplant neuropil appeared to intermingle.
      CMP data indicate that horizontal cells and both glycinergic and GABAergic
      amacrine cells are involved in a novel circuit between transplant and host,
      generating alternative signal pathways between transplant and degenerating host
      retina.

PMID- 22594838
TI  - Endothelin-1 derived from spleen-activated Rho-kinase pathway in rats with
      secondary biliary cirrhosis.
AB  - AIM:   Splenectomy or partial splenic embolism has been reported to improve liver
      function in patients with hypersplenism and liver dysfunction. The aim of this
      study was to investigate the mechanism of improvement after splenectomy. METHODS:
      Liver cirrhosis was induced by bile duct ligation (BDL). Rats underwent sham
      operation, splenectomy (Sp group), BDL, or BDL plus splenectomy (BDL + Sp group),
      and were subjected to experiments at 2 weeks after the operation. Portal venous
      pressure (PVP) and hepatic tissue blood flow (HTBF) were measured in each group.
      The plasma concentration of endothelin-1 (ET-1) and endothelial nitric oxide
      synthase (eNOS), RhoA and Rho-kinase expressions were studied. RESULTS:   There
      were significant differences in PVP (17.9 +/- 0.91 vs 23.3 +/- 3.91 cmH(2) O; P <
      0.01) and HTBF (16.6 +/- 1.72 vs 13.3 +/- 1.82 mL/min; P < 0.01) between the BDL
      + Sp and BDL groups. In the liver of BDL rats, eNOS phosphorylation and NOx
      levels were decreased, accompanied by RhoA activation compared with the BDL + Sp
      group. Splenectomy decreased serum ET-1 levels, RhoA activation and consequently
      increased eNOS phosphorylation. CONCLUSION:   ET-1 derived from the spleen might
      increase intrahepatic resistance by downregulating Rho signaling in liver
      cirrhosis. Splenectomy for splenomegaly in liver cirrhosis might partially
      improve liver function by enhancing intrahepatic microcirculation.

PMID- 22594839
TI  - Establishing aluminium contact allergy.
AB  - BACKGROUND: Traditionally, contact allergy to aluminium has been established by
      patch testing with aluminium chloride hexahydrate in petrolatum at 2.0% and an
      empty Finn Chamber(r). OBJECTIVES: The aim of this study was to investigate
      different aluminium test preparations regarding an optimal compound and an
      optimal test concentration. METHODS: Six different aluminium compounds and an
      empty Finn Chamber(r) were used to patch test 21 patients with aluminium contact
      allergy. Aluminium chloride hexahydrate in saline was used for intracutaneous
      injection of 19 patients. RESULTS: One test preparation, aluminium lactate 2.4%,
      was found to show significantly more positive patch test reactions than aluminium
      chloride hexahydrate 2.0% (p = 0.03). Aluminium chloride hexahydrate at 10.0%
      pet. gave the highest number of positive reactions to aluminium [14/21 (67%)]. No
      positive reactions were noted to an empty Finn Chamber(r), and 3 of 19 (16%)
      patients reacted positively to the intradermal test. CONCLUSIONS: The results of
      this study indicate that patch testing with aluminium chloride hexahydrate 2.0%,
      with an empty Finn Chamber(r) and the intradermal test with the salt and doses
      used are insufficient methods to detect contact allergy to aluminium. Aluminium
      chloride hexahydrate at 10.0% gave the highest number of positive reactions to
      aluminium.

PMID- 22594840
TI  - Isolation of a new phlorotannin, a potent inhibitor of carbohydrate-hydrolyzing
      enzymes, from the brown alga Sargassum patens.
AB  - Ethanol extracts from 15 kinds of marine algae collected from the coast of the
      Noto Peninsula in Japan were examined for their inhibitory effects on human
      salivary alpha-amylase. Four extracts significantly suppressed the enzyme
      activity. An inhibitor was purified from the extract of  Sargassum patens . The
      compound was a new phloroglucinol derivative, 2-(4-(3,5-dihydroxyphenoxy)-3,5
      dihydroxyphenoxy) benzene-1,3,5-triol (DDBT), which strongly suppressed the
      hydrolysis of amylopectin by human salivary and pancreatic alpha-amylases. The
      50% inhibitory activity (IC(50)) for alpha-amylase inhibition of DDBT (3.2
      MUg/mL) was much lower than that of commercially available alpha-amylase
      inhibitors, acarbose (26.3 MUg/mL), quercetagetin (764 MUg/mL), and alpha-amylase
      inhibitor from  Triticum aestivum  (88.3 MUg/mL). A kinetic study indicated that
      DDBT was a competitive alpha-amylase inhibitor with a K(i) of 1.8 MUg/mL. DDBT
      also inhibited rat intestinal alpha-glucosidase with an IC(50) value of 25.4
      MUg/mL for sucrase activity and 114 MUg/mL for maltase activity. These results
      suggest that DDBT, a potent inhibitor of carbohydrate-hydrolyzing enzymes, may be
      useful as a natural nutraceutical to prevent diabetes.

PMID- 22594841
TI  - A pilot study for targeted surveillance of bovine spongiform encephalopathy in
      Nigeria.
AB  - Bovine spongiform encephalopathy (BSE), popularly known as 'mad cow disease', led
      to an epidemic in Europe that peaked in the mid-1990s. Its impact on developing
      countries, such as Nigeria, has not been fully established as information on
      livestock and surveillance has eluded those in charge of this task. The BSE risk
      to Nigeria's cattle population currently remains undetermined, which has resulted
      in international trade restrictions on commodities from the cattle population.
      This is mainly because of a lack of updated BSE risk assessments and disease
      surveillance data. To evaluate the feasibility of BSE surveillance in Nigeria, we
      carried out a pilot study targeting cattle that were presented for emergency or
      casualty slaughter. In total, 1551 cattle of local breeds, aged 24 months and
      above were clinically examined. Ataxia, recumbency and other neurological signs
      were topmost on our list of criteria. A total of 96 cattle, which correspond to
      6.2%, presented clinical signs that supported a suspect of BSE. The caudal
      brainstem tissues of these animals were collected post-mortem and analysed for
      the disease-specific form of the prion protein using a rapid test approved by the
      International Animal Health Organization (OIE). None of the samples were positive
      for BSE. Although our findings do not exclude the presence of BSE in Nigeria,
      they do demonstrate that targeted sampling of clinically suspected cases of BSE
      is feasible in developing countries. In addition, these findings point to the
      possibility of implementing clinical monitoring schemes for BSE and potentially
      other diseases with grave economic and public health consequences.

PMID- 22594843
TI  - Expert reviews: who are they for?

PMID- 22594844
TI  - Alfuzosin for the treatment of storage symptoms suggestive of overactive bladder.
AB  - INTRODUCTION: Antimuscarinics are the mainstay of overactive bladder (OAB)
      pharmacotherapy although other agents, such as alpha-adrenergic receptor
      antagonists, might also be effective. Alfuzosin has alpha1-adrenoreceptor
      antagonist activity and is available worldwide for the treatment of lower urinary
      tract symptoms resulting from benign prostate hyperplasia. Alfuzosin may relieve
      storage symptoms suggestive of OAB in patients with or without bladder outlet
      obstruction (BOO). AREAS COVERED: This paper reviews the available literature on
      the use of alfuzosin in the treatment of storage symptoms suggestive of OAB.
      Additionally, the role of alpha-adrenoreceptor antagonists in the treatment of
      OAB is reviewed, based on pathophysiology. EXPERT OPINION: Although alfuzosin is
      effective against storage symptoms, it does not improve them in all patients with
      OAB. It is likely that alternative types of therapy, such as antimuscrarinics,
      need to be co-administered to patients with residual storage symptoms after
      alfuzosin administration. Alfuzosin can decrease the risk of adverse events
      associated with antimuscarinics. The sequential use of alfuzosin and
      antimuscarinics appears to be an appropriate strategy for the treatment of
      storage symptoms suggestive of OAB related to BOO.

PMID- 22594845
TI  - Targeting reperfusion injury in acute myocardial infarction: a review of
      reperfusion injury pharmacotherapy.
AB  - INTRODUCTION: Acute myocardial infarction (AMI) (secondary to lethal ischemia
      reperfusion [IR]) contributes to much of the mortality and morbidity from
      ischemic heart disease. Currently, the treatment for AMI is early reperfusion;
      however, this itself contributes to the final myocardial infarct size, in the
      form of what has been termed 'lethal reperfusion injury'. Over the last few
      decades, the discovery of the phenomena of ischemic preconditioning and
      postconditioning, as well as remote preconditioning and remote postconditioning,
      along with significant advances in our understanding of the cardioprotective
      pathways underlying these phenomena, have provided the possibility of successful
      mechanical and pharmacological interventions against reperfusion injury. AREAS
      COVERED: This review summarizes the evidence from clinical trials evaluating
      pharmacological agents as adjuncts to standard reperfusion therapy for ST
      elevation AMI. EXPERT OPINION: Reperfusion injury pharmacotherapy has moved from
      bench to bedside, with clinical evaluation and ongoing clinical trials providing
      us with valuable insights into the shortcomings of current research in
      establishing successful treatments for reducing reperfusion injury. There is a
      need to address some key issues that may be leading to lack of translation of
      cardioprotection seen in basic models to the clinical setting. These issues are
      discussed in the Expert opinion section.

PMID- 22594846
TI  - Ceftaroline fosamil  for community-acquired bacterial pneumonia and acute
      bacterial skin and skin structure infection.
AB  - INTRODUCTION: Bacterial resistance is increasing on a global basis, making
      treatment options more limited. The development of new agents to meet this threat
      is a matter of urgency. Ceftaroline fosamil , a member of an advanced
      cephalosporin class of antimicrobials, is currently approved by the US Food and
      Drug Administration for use in for acute bacterial skin and skin structure
      infection (ABSSSI) and community-acquired bacterial pneumonia. Ceftaroline
      displays activity against Gram-positive and Gram-negative bacteria, including
      both methicillin-susceptible and resistant Staphylococcus aureus (MRSA),
      Streptococcus pneumoniae (including penicillin- and ceftriaxone-resistant
      strains), respiratory pathogens (such as Moraxella catarrhalis and Haemophilus
      influenzae, including beta-lactamase-producing strains) and limited coverage
      against Enterobacteriaceae. AREAS COVERED: Chemistry, mechanism of action,
      spectrum of activity, resistance, pharmacokinetics/pharmacodynamics, indications
      for use, safety and special populations are covered in this review. EXPERT
      OPINION: Ceftaroline's unique activity against MRSA and penicillin- and
      ceftriaxone-resistant S. pneumoniae strains is due to its high affinity for
      penicillin binding protein (PBP)-2a and PBP-2x, respectively. In randomized,
      double-blinded, clinical trials, ceftaroline fosamil was found to be non-inferior
      to ceftriaxone for the treatment CABP and to vancomycin plus aztreonam for
      ABSSSI. Substantial differences between the cephalosporins exist. Ceftaroline has
      unique characteristics that may make it useful in specific clinical
      circumstances, especially against multi-drug-resistant Gram-positive organisms.

PMID- 22594847
TI  - Crizotinib  in the treatment of non-small-cell lung cancer.
AB  - INTRODUCTION: Recent progress in identifying distinct subsets of lung cancer,
      based on critical driver mutations, has led to increasingly focused efforts in
      the development of selectively targeted therapies. The fusion oncogene,
      echinoderm microtubule-associated protein-like 4 - anaplastic lymphoma kinase
      (EML4-ALK), is present in approximately 5% of non-small-cell lung cancer (NSCLC)
      tumors. Crizotinib is an oral tyrosine kinase inhibitor (TKI), which silences the
      protein product of the ALK fusion gene and has recently been approved for the
      treatment of NSCLC aberrantly expressing ALK. Emerging data suggest that
      crizotinib may also have activity in other subsets of lung cancer, including
      tumors demonstrating amplification or mutation of the MET oncogene, or
      translocation of the ROS1 oncogene. AREAS COVERED: This paper gives an overview
      of the molecular pathogenesis of ALK-associated NSCLC. It also reviews the
      pharmacokinetic and pharmacodynamic data on crizotinib and outlines the
      preclinical and clinical studies leading to the approval of crizotinib. In
      addition, it discusses its role in the treatment of NSCLC expressing ALK. EXPERT
      OPINION: Crizotinib represents the newest example of a focused strategy for drug
      development in lung cancer, based on identification and targeted inhibition of
      critical tumor-specific driver mutations. Crizotinib has demonstrated efficacy
      against ALK-rearranged NSCLC, and has potential for broader application in select
      subsets of lung cancer.

PMID- 22594848
TI  - Levofloxacin  for the treatment of respiratory tract infections.
AB  - INTRODUCTION: Fluoroquinolone use has dramatically increased since the
      introduction of the first respiratory fluoroquinolone in the late 1990s.
      Levofloxacin , like other fluoquinolones, is a potent antibiotic, due to high
      levels of susceptibility among Gram-negative, Gram-positive (including penicillin
      resistant strains of Streptococcus pneumonia) and atypical pathogens.
      Levofloxacin is recommended for the treatment of community-acquired pneumonia
      (CAP), hospital-acquired pneumonia (HAP) and in the management of acute
      exacerbations of chronic bronchitis (AECB). Levofloxacin demonstrates good
      safety, bioavailability and tissue penetration, thus maintaining adequate
      concentrations at the site of infection. High-dose (750 mg), short-course (5
      days) therapy regimens may offer improved treatment, especially in HAP, due to
      higher drug concentrations, increased adherence and the potential to reduce the
      development of resistance. AREAS COVERED: This article covers medical literature
      published in any language since 1990 until November 2011, on 'levofloxacin',
      identified using PubMed and MEDLINE. The search terms used were 'levofloxacin'
      and 'community acquired pneumonia', 'hospital pneumonia' or 'AECB'. EXPERT
      OPINION: Levofloxacin is a valuable antimicrobial agent and an optimal treatment
      option for AECB, CAP (as a monotherapy) and HAP (as combination therapy at a high
      dose regimen). Its improved bioavailability and safety profile makes the
      possibility of shorter hospital stays a reality.

PMID- 22594849
TI  - Lamotrigine use in pregnancy.
AB  - Lamotrigine is a sodium-channel-modulating, antiepileptic drug (AED), which was
      approved in the USA in 1994 for use in partial-onset seizures. It was ultimately
      approved for monotherapy in 1998. Lamotrigine has gained widespread use in the
      USA as both an immediate and an extended-release agent. Lamotrigine is effective
      against a broad spectrum of seizure types and has a favorable metabolic profile,
      with few but significant drug interactions. Pregnancy registries in several
      countries have demonstrated that AED use in women with epilepsy is associated
      with an increased risk of fetal malformations, if the infant is exposed during
      the period of organogenesis. In addition, new evidence demonstrates that AEDs may
      affect the intellectual development of a child, as measured up until the age of 3
      years. This information has made the choice of an anticonvulsant for a woman who
      might become pregnant significantly more important. Pregnancy registries have
      consistently demonstrated lamotrigine to be among the safest medications for a
      developing fetus, both in terms of fetal malformations and postpartum cognitive
      development. These findings make lamotrigine probably the first choice of AED for
      women wishing to become pregnant and for whom the medication is appropriate.

PMID- 22594851
TI  - Commentary on Wagener et al. (2012): laissez-faire regulation: turning back the
      clock on the Food and Drug Administration and public health.

PMID- 22594850
TI  - Author's response: expert reviews: who are they for?

PMID- 22594852
TI  - Corona discharge ion mobility spectrometry with orthogonal acceleration time of
      flight mass spectrometry for monitoring of volatile organic compounds.
AB  - We demonstrate the application of corona discharge ion mobility spectrometry with
      orthogonal acceleration time of flight mass spectrometry (CD IMS-oaTOF) for
      volatile organic compounds (VOCs) monitoring. Two-dimensional (2D) IMS-oaTOF
      spectra of VOCs were recorded in nearly real time. The corona discharge
      atmospheric pressure chemical ionization (APCI) source was operated in positive
      mode in nitrogen and air. The CD ion source generates in air H(3)O(+)(H(2)O)(n)
      and NO(+). The NO(+) offers additional possibility for selective ionization and
      for an increase of the sensitivity of monoaromatic compounds. In addition to
      H(3)O(+)(H(2)O)(n) and NO(+), we have carried out ionization of VOCs using
      acetone as dopant gas ((CH(3))(2)COH(+)). Sixteen model VOCs (tetrahydrofuran,
      butanol, n-propanol, iso-propano, acetone, methanol, ethanol, toluene, benzene,
      amomnia, dioxan, triethylamine, acetonitrile, formaldehyde, m-xylene, 2,2,2
      trifluoroethylamine) were tested using these ionization techniques.

PMID- 22594853
TI  - Lead(II) complex formation with glutathione.
AB  - A structural investigation of complexes formed between the Pb(2+) ion and
      glutathione (GSH, denoted AH(3) in its triprotonated form), the most abundant
      nonprotein thiol in biological systems, was carried out for a series of aqueous
      solutions at pH 8.5 and C(Pb(2+)) = 10 mM and in the solid state. The Pb L(III)
      edge extended X-ray absorption fine structure (EXAFS) oscillation for a solid
      compound with the empirical formula [Pb(AH(2))]ClO(4) was modeled with one Pb-S
      and two short Pb-O bond distances at 2.64 +/- 0.04 and 2.28 +/- 0.04 A,
      respectively. In addition, Pb...Pb interactions at 4.15 +/- 0.05 A indicate
      dimeric species in a network where the thiolate group forms an asymmetrical
      bridge between two Pb(2+) ions. In aqueous solution at the mole ratio GSH/Pb(II)
      = 2.0 (C(Pb(2+)) = 10 mM, pH 8.5), lead(II) complexes with two thiolate ligands
      form, characterized by a ligand-to-metal charge-transfer band (LMCT) S(-) ->
      Pb(2+) at 317 nm in the UV-vis spectrum and mean Pb-S and Pb-(N/O) bond distances
      of 2.65 +/- 0.04 and 2.51 +/- 0.04 A, respectively, from a Pb L(III)-edge EXAFS
      spectrum. For solutions with higher mole ratios, GSH/Pb(II) >= 3.0, electrospray
      ionization mass spectroscopy spectra identified a triglutathionyllead(II)
      complex, for which Pb L(III)-edge EXAFS spectroscopy shows a mean Pb-S distance
      of 2.65 +/- 0.04 A in PbS(3) coordination, (207)Pb NMR spectroscopy displays a
      chemical shift of 2793 ppm, and in the UV-vis spectrum, an S(-) -> Pb(2+) LMCT
      band appears at 335 nm. The complex persists at high excess of GSH and also at
      ~25 K in frozen glycerol (33%)/water glasses for GSH/Pb(II) mole ratios from 4.0
      to 10 (C(Pb(2+)) = 10 mM) measured by Pb L(III)-edge EXAFS spectroscopy.

PMID- 22594855
TI  - The prognostic impact of clinical and molecular features in hairy cell leukaemia
      variant and splenic marginal zone lymphoma.
AB  - Hairy cell leukaemia variant (HCL-variant) and splenic marginal zone lymphoma
      (SMZL) are disorders with overlapping features. We investigated the prognostic
      impact in these disorders of clinical and molecular features including IGH VDJ
      rearrangements, IGHV gene usage and TP 53 mutations. Clinical and laboratory data
      were collected before therapy from 35 HCL-variant and 68 SMZL cases. End-points
      were the need for treatment and overall survival. 97% of HCL-variant and 77% of
      SMZL cases required treatment (P = 0.009). Survival at 5 years was significantly
      worse in HCL-variant [57% (95% confidence interval 38-73%)] compared with SMZL
      [84% (71-91%); Hazard Ratio 2.25 (1.20-4.25), P = 0.01]. In HCL-variant, adverse
      prognostic factors for survival were older age (P = 0.04), anaemia (P = 0.01) and
      TP 53 mutations (P = 0.02). In SMZL, splenomegaly, anaemia and IGHV genes with
      >98% homology to the germline predicted the need for treatment; older age,
      anaemia and IGHV unmutated genes (100% homology) predicted shorter survival. IGHV
      gene usage had no impact on clinical outcome in either disease. The combination
      of unfavourable factors allowed patients to be stratified into risk groups with
      significant differences in survival. Although HCL-variant and SMZL share some
      features, they have different outcomes, influenced by clinical and biological
      factors.

PMID- 22594854
TI  - Sweetpotato-based complementary food would be less inhibitory on mineral
      absorption than a maize-based infant food assessed by compositional analysis.
AB  - The availability of micronutrients from sweetpotato-based complementary foods
      (CFs): oven-toasted and roller-dried ComFa, and from a maize-based infant food,
      enriched Weanimix, was compared using phytate/mineral molar ratios, polyphenols
      and beta-carotene levels. The phytate/calcium, iron and zinc molar ratios of
      approximately 0.17, 1 and 15 predict better absorption of calcium, iron and zinc
      respectively. Generally, the sweetpotato-based CFs had at least half the
      phytate/mineral ratios of enriched Weanimix. The phytate/iron ratio in both the
      sweetpotato- and the maize-based CFs was greater than 1. Only the ComFa
      formulations had phytate/zinc ratio lower than 15. The level of polyphenol (iron
      inhibitor) was similar for the formulations. Only the sweetpotato-based CFs
      contained measurable levels of beta-carotene, a possible iron enhancer. The lower
      phytate/mineral ratios and the beta-carotene level of the sweetpotato-based CFs
      suggest that calcium, iron and zinc absorption could be better from them than
      from the maize-based infant food.

PMID- 22594856
TI  - The role of mental health, personality disorders and childhood adversities in
      relation to life satisfaction in a sample of general population.
AB  - BACKGROUND: Mental health disorders are one of the leading causes of the disease
      burden globally. AIM: The aim of this population-based study was to investigate
      the relationship between life satisfaction and mental health by taking into
      account its less studied areas, such as personality disorders and childhood
      adversities. METHODS: The sample of this cross-sectional study was derived from a
      population-based Kuopio Depression Study performed in Eastern Finland. Health
      questionnaires were mailed in 1998, 1999, 2001 and 2005 including questions on
      several clinical factors. Questions on childhood home were asked in 1999. The
      inclusion criteria for the final study sample in 2005 were based on previously
      repeatedly (1998, 1999, 2001) reported life satisfaction, depression or
      alexithymic features (with/without). Psychiatric diagnoses of major depressive
      disorder and personality disorder were confirmed by structured clinical interview
      I and II for DSM-IV in 2005. Logistic regression analyses were performed to
      assess the studied relationships. RESULTS: In general, the broad spectrum of poor
      mental health indicators was associated with concurrent life dissatisfaction.
      After multiple adjustments, major depressive disorder (MDD), hopelessness and
      mental distress remained independent correlates of life dissatisfaction, while
      personality disorder or self-reported childhood adversities lost their
      significance when these other factors were included in the model. CONCLUSIONS:
      Mental health is closely interwoven with life satisfaction. Even if personality
      disorder and childhood adversities were significant correlates of life
      dissatisfaction, adverse concurrent mental symptoms and features and MDD were its
      strongest correlates.

PMID- 22594859
TI  - Dyschromatosis symmetrica hereditaria: a case report from Turkey, a new
      association and a novel gene mutation.

PMID- 22594858
TI  - Thermotherapy. An alternative for the treatment of American cutaneous
      leishmaniasis.
AB  - BACKGROUND: Pentavalent antimonials (Sb5) and miltefosine are the first-line
      drugs for treating cutaneous leishmaniasis in Colombia; however, toxicity and
      treatment duration negatively impact compliance and cost, justifying an active
      search for better therapeutic options. We compared the efficacy and safety of
      thermotherapy and meglumine antimoniate for the treatment of cutaneous
      leishmaniasis in Colombia. METHOD: An open randomized Phase III clinical trial
      was performed in five military health centres. located in northwestern, central
      and southern Colombia. Volunteers with parasitological positive diagnosis (Giemsa
      stained smears) of cutaneous leishmaniasis were included. A single thermotherapy
      session involving the application of 50 degrees C at the center and active edge
      of each lesion. Meglumine antimoniate was administered intramuscularly at a dose
      of 20 mg Sb5/kg weight/day for 20 days. RESULTS: Both groups were comparable. The
      efficacy of thermotherapy was 64% (86/134 patients) by protocol and 58% (86/149)
      by intention-to-treat. For the meglumine antimoniate group, efficacy by protocol
      was 85% (103/121 patients) and 72% (103/143) by intention-to-treat, The efficacy
      between the treatments was statistically significant (p 0.01 and < 0.001) for
      analysis by intention to treat and by protocol, respectively. There was no
      difference between the therapeutic response with either treatment regardless of
      the Leishmania species responsible for infection. The side effects of meglumine
      antimoniate included myalgia, arthralgia, headache and fever. Regarding
      thermotherapy, the only side effect was pain at the lesion area four days after
      the initiation of treatment. CONCLUSION: Although the efficacy rate of meglumine
      antimoniate was greater than that of thermotherapy for the treatment of cutaneous
      leishmaniasis, the side effects were also greater. Those factors, added to the
      increased costs, the treatment adherence problems and the progressive lack of
      therapeutic response, make us consider thermotherapy as a first line treatment
      for cutaneous leishmaniasis.

PMID- 22594861
TI  - Adenomyosis: a challenge in clinical gynecology.
AB  - Adenomyosis is a prevalent, benign gynecologic condition in which endometrial
      tissue invades the myometrium, causing myometrial inflammation and hypertrophy.
      Although some women with adenomyosis are asymptomatic, the condition often causes
      menorrhagia and dysmenorrhea. This article provides women's health providers with
      a review of causes and risk factors for developing adenomyosis, clinical
      presentations of women with the condition, diagnostic modalities and criteria,
      and medical and surgical treatment options.

PMID- 22594862
TI  - Polycystic ovary syndrome: a common but often unrecognized condition.
AB  - Polycystic ovary syndrome (PCOS) affects 5% to 10% of women of reproductive age,
      with symptoms often presenting during adolescence and young adulthood. It is a
      condition characterized by (1) hyperandrogenism, (2) oligomenorrhea or
      amenorrhea, and (3) polycystic ovaries. This syndrome is associated with
      significant endocrine, metabolic, cardiovascular, reproductive, and psychiatric
      morbidities. Although the diagnosis of PCOS is based on the presence of at least
      2 of the 3 criteria that characterize the condition, the syndrome has a broad
      spectrum of clinical features that may signal its presence. Evidence suggests
      that many women with clinical features of PCOS remain undiagnosed, placing them
      at an increased risk for developing complications associated with the syndrome.
      This review presents current information about the pathophysiology, clinical
      features, diagnosis, and recommended treatments for PCOS.

PMID- 22594863
TI  - Assessment and management options for women with vulvodynia.
AB  - Vulvodynia is a chronic pain disorder that affects sexual function in adult
      women. The etiology of vulvodynia is poorly understood, making the condition
      difficult to diagnose and treat. Women with vulvodynia often suffer significant
      psychological distress and have difficulty finding a compassionate and supportive
      health care provider. This article reviews the etiology, diagnosis, educational
      strategies, and treatment options for vulvodynia with the aim of increasing
      primary care providers' knowledge and assessment skills. Physical therapy and
      other nonsurgical treatment modalities are explored in depth.

PMID- 22594864
TI  - Abnormal uterine bleeding during the reproductive years.
AB  - Abnormal uterine bleeding is one of the most common reasons that reproductive
      aged women seek health care. The causes are varied, depending in large part on
      the age and life stage of the woman. Thus, diagnosis requires a systematic
      approach that is driven by a thorough health history and review of presenting
      symptoms. In recent years, the treatment of abnormal uterine bleeding has moved
      away from surgical procedures in favor of more conservative, yet effective,
      hormonal therapy such as combined contraceptives and the levonorgestrel-releasing
      intrauterine system. Clinicians must be knowledgeable about the various abnormal
      uterine bleeding treatment options and partner with women to develop appropriate,
      individualized treatment plans. The purpose of this article is to synthesize the
      current literature to describe the contributing etiologies, common presentations,
      diagnosis, evaluation, and management of abnormal uterine bleeding.

PMID- 22594865
TI  - Recognition and management of vulvar dermatologic conditions: lichen sclerosus,
      lichen planus, and lichen simplex chronicus.
AB  - Lichen sclerosus, lichen planus, and lichen simplex chronicus are dermatologic
      conditions that can affect the vulva. Symptoms include vulvar itching,
      irritation, burning, and pain, which may be chronic or recurrent and can lead to
      significant physical discomfort and emotional distress that can affect mood and
      sexual relationships. With symptoms similar to common vaginal infections, women
      often seek care from gynecological providers and may be treated for vaginal
      infections without relief. Recognition and treatment of these vulvar conditions
      is important for symptom relief, sexual function, prevention of progressive
      vulvar scarring, and to provide surveillance for associated vulvar cancer. This
      article reviews these conditions including signs and symptoms, the process of
      evaluation, treatment, and follow-up, with attention to education and guidelines
      for vulvar care and hygiene.

PMID- 22594866
TI  - What's new in sexually transmitted infection management: changes in the 2010
      guidelines from the Centers for Disease Control and Prevention.
AB  - Screening, treatment, and follow-up of sexually transmitted infections (STIs) are
      an important part of the role of women's health care providers. Keeping abreast
      of new and changing treatment guidelines is crucial to providing competent care.
      The Sexually transmitted diseases treatment guidelines, produced every 4 years by
      the Centers for Disease Control and Prevention, summarize current evidence on
      prevention, diagnosis, and treatment of STIs. The purpose of this article is to
      review the changes in the 2010 guidelines from the previous 2006 guidelines.
      These changes include new diagnostic tests for bacterial vaginosis, Neisseria
      gonorrhoeae, and human papillomavirus; new treatment recommendations for
      bacterial vaginosis, gonorrhea, and genital warts; the increasing prevalence of
      antimicrobial-resistant N gonorrhoeae; new criteria for spinal fluid examination
      to evaluate for neurosyphilis; and the emergence of azithromycin-resistant
      Treponema pallidum.

PMID- 22594867
TI  - Midwives and abortion care: a model for achieving competency.
AB  - Throughout history, the care of women's reproductive health needs has included
      termination of unwanted pregnancy. Unfortunately, access to safe first-trimester
      abortion is restricted by a lack of skilled providers. In an effort to provide
      data-based evidence and increase access to first-trimester abortion care in
      California, the University of California, San Francisco, under the auspices of
      the Health Workforce Pilot Program, developed a competency-based training model
      to increase the number of certified nurse-midwives, nurse practitioners, and
      physician assistants who can provide uterine aspiration. This article describes
      the training program, which uses a curriculum comprising both self-directed
      didactic material and supervised clinical experience with a minimum of 40
      procedures. Successful completion of the program requires passing a written
      examination and satisfactory achievement of a competency-based clinical
      assessment. Thirty-eight trainees have completed the training to date, achieving
      competency following an average of 6 training days. Competency development in the
      clinical area is monitored by both the trainer and the trainee, using daily and
      final competency assessments in 4 domains: patient comfort, procedural
      completeness, speed, and ability to identify problems. Analysis of complications
      is used to identify concerns about clinician safety. The availability of a
      competency-based training curriculum for uterine aspiration has the potential to
      increase the number of first-trimester abortion providers by making training
      available to experienced clinicians, including nurse-midwives, who would like to
      provide this care.

PMID- 22594869
TI  - Moving from high to lower level poverty neighborhoods may reduce prevalence of
      extreme obesity and diabetes.

PMID- 22594868
TI  - Vulvar skin atrophy induced by topical glucocorticoids.
AB  - Steroid-induced skin atrophy is the most frequent and perhaps most important
      cutaneous side effect of topical glucocorticoid therapy. To date, it has not been
      described in vulvar skin. A patient presented with significant vulvar skin
      atrophy following prolonged steroid application to treat vulvar dermatitis. The
      extensive atrophy in the perineum resulted in secondary "webbing" and partial
      obstruction of the genital hiatus and superimposed dyspareunia. Prolonged use of
      topical steroids may result in atrophic changes in vulvar skin. Further research
      in clinical correlates of steroid-induced atrophy in the vulvar region is
      warranted.

PMID- 22594872
TI  - Share with women. Vulvodynia.

PMID- 22594873
TI  - Share with women. Vulvar care.

PMID- 22594874
TI  - Disulfide bonds: protein folding and subcellular protein trafficking.
AB  - The study of disulfide-bond-containing proteins has advanced our understanding of
      the mechanism(s) by which the majority of secretory and membrane-bound proteins
      acquire their biologically functional folded forms. This covalent linkage has
      been exploited by a number of research laboratories to harness or trap
      intermediates populating the folding trajectories of biopolymers. The resulting
      body of gathered in vitro data demonstrates that, in general, there is a common
      event underscoring the maturation of disulfide-bond-containing proteins. This
      commonality is the existence of competition between a physical, conformational
      folding reaction and a chemical, thiol-disulfide exchange reaction during fold
      acquisition. The competition, in turn, impacts the fate of the polypeptide in
      being secreted or retrotranslocated. The role of a host of subcellular factors,
      including protein disulfide isomerase, that influences this critical
      spatiotemporal juncture of the fold-maturation process is discussed. Finally, the
      impact of this competition on the onset of neurodegenerative disorders is
      elaborated upon.

PMID- 22594875
TI  - Multiple injuries after earthquakes: a retrospective analysis on 1,871 injured
      patients from the 2008 Wenchuan earthquake.
AB  - INTRODUCTION: Multiple injuries have been highlighted as an important clinical
      dimension of the injury profile following earthquakes, but studies are scarce. We
      investigated the pattern and combination of injuries among patients with two
      injuries following the 2008 Wenchuan earthquake. We also described the general
      injury profile, causes of injury and socio-demographic characteristics of the
      injured patients. METHODS: A retrospective hospital-based analysis of 1,871
      earthquake injured patients, totaling 3,177 injuries, admitted between 12 and 31
      May 2008 to the People's Hospital of Deyang city (PHDC). An electronic, webserver
      based database with International Classification of Diseases (ICD)-10-based
      classification of earthquake-related injury diagnoses (IDs), anatomical sites and
      additional background variables of the inpatients was used. We analyzed this
      dataset for injury profile and number of injuries per patient. We then included
      all patients (856) with two injuries for more in-depth analysis. Possible spatial
      anatomical associations were determined a priori. Cross-tabulation and more
      complex frequency matrices for combination analyses were used to investigate the
      injury profile. RESULTS: Out of the 1,871 injured patients, 810 (43.3%) presented
      with a single injury. The rest had multiple injuries; 856 (45.8%) had two, 169
      (9.0%) patients had three, 32 (1.7%) presented with four injuries, while only 4
      (0.2%) were diagnosed with five injuries. The injury diagnoses of patients
      presenting with two-injuries showed important anatomical intra-site or
      neighboring clustering, which explained 49.1% of the combinations. For fractures,
      the result was even more marked as spatial clustering explained 57.9% of the
      association pattern. The most frequent combination of IDs was a double-fracture,
      affecting 20.7% of the two-injury patients (n = 177). Another 108 patients
      (12.6%) presented with fractures associated with crush injury and organ-soft
      tissue injury. Of the 3,177 injuries, 1,476 (46.5%) were fractures. Most injuries
      were located in the head (22.9%) and lower extremities (30.8%). CONCLUSIONS:
      Multiple injuries are put forward as an important component of the injury profile
      after this earthquake. A pattern of injury combinations and spatial aggregation
      of injuries was also found. Clinical diagnosis and treatment should be adapted to
      care of these patients. More studies are needed to generalize these findings.

PMID- 22594876
TI  - Sociodemographic factors and utilization of eye care services: is there an
      association with patients presenting to a tertiary referral hospital in acute
      angle-closure?
AB  - BACKGROUND: The aim of this study is to examine the relationship between
      sociodemographic factors and utilization of eye care services in patients
      presenting in acute angle-closure (AAC). DESIGN: A hospital-based retrospective,
      case-control study. PARTICIPANTS: Fifty-five patients consecutively presenting to
      the emergency department of the Royal Victorian Eye and Ear Hospital with AAC
      (cases), and 43 patients consecutively referred to the outpatient department for
      prophylactic laser peripheral iridotomy (controls) over a 3-year period. METHODS:
      Standardized telephone questionnaires. MAIN OUTCOME MEASURES: Comparisons were
      made for sociodemographic factors, utilization of eye care services and provision
      of information on glaucoma and premonitory symptoms of AAC. RESULTS: No
      significant differences across a range of socioeconomic and demographic factors
      were found. Fewer cases reported having attended an eye care professional ever (P
      = 0.02), or in the 12 months preceding their acute hospital attendance (P =
      0.002), and had less awareness of angle closure glaucoma (P = 0.001). Logistic
      regression modelling demonstrated premonitory symptoms of AAC (odds ratio 3.96,
      [95% confidence interval 1.52-10.32], P < 0.001) and a period of greater than 12
      months since the last eye examination (odds ratio 3.89, [95% confidence interval
      1.64-9.21]) were significantly associated with the risk of AAC. CONCLUSIONS: No
      significant differences in socioeconomic or demographic parameters between cases
      and controls were identified. Control subjects had a history of more frequent and
      recent access to eye care services than cases. The finding that more than one
      third of patients presenting with AAC had consulted an eye care provider in the
      preceding year suggests that a significant proportion of individuals at risk of
      AAC remain undetected.

PMID- 22594878
TI  - Untangling asthma phenotypes and endotypes.
AB  - Asthma phenotypes have been developed to address the complexities of the disease.
      However, owing to a lack of longitudinal studies, little is known about the onset
      as well as the stability of phenotypes. Distinguishing phenotypes with regard to
      the severity or duration of the disease is essential. A phenotype covers the
      clinically relevant properties of the disease, but does not show the direct
      relationship to disease etiology and pathophysiology. Different pathogenetic
      mechanisms might cause similar asthma symptoms and might be operant in a certain
      phenotype. These putative mechanisms are addressed by the term 'endotype'.
      Classification of asthma based on endotypes provides advantages for
      epidemiological, genetic, and drug-related studies. A successful definition of
      endotypes should link key pathogenic mechanisms with the asthma phenotype. Thus,
      the identification of corresponding molecular biomarkers for individual
      pathogenic mechanism underlying phenotypes or subgroups within a phenotype is
      important. Whether newly defined asthma endotypes predict the individual course
      of asthma has to be validated in longitudinal studies. The accurate endotyping
      reflects natural history of asthma and should help to predict treatment response.
      Thus, understanding asthma endotypes might be useful in clinical practice.

PMID- 22594877
TI  - Microtubule stabilization by peloruside A and paclitaxel rescues degenerating
      neurons from okadaic acid-induced tau phosphorylation.
AB  - Many cellular organelles must travel long distances in neurons to perform their
      specific functions, and this transport is highly dependent on the microtubule
      network within the axon. Hyperphosphorylation of microtubule-associated tau
      protein destabilizes microtubules and leads to neuronal cell death. This
      destabilization can be corrected in part by treatment with microtubule
      stabilizing drugs such as paclitaxel and epothilone. The phosphatase inhibitor
      okadaic acid inhibits the outgrowth of neurites in neuronal cell cultures by
      hyperphosphorylating tau protein. In this study using neuronal cultures derived
      from the cerebral cortex of early postnatal Sprague-Dawley rats, we examined
      whether stabilization of microtubules by peloruside A, a microtubule-stabilizing
      agent that binds to a different site on beta-tubulin from paclitaxel, could
      counter the deleterious effects of 8 h exposure to 15 nm okadaic acid. Peloruside
      A reversed the decrease in axonal outgrowth and branching seen in neuronal
      cultures treated with okadaic acid and rescued neurons from growth cone collapse.
      Although peloruside A had no effect on the hyperphosphorylation of tau caused by
      okadaic acid, it restored the levels of acetylated tubulin, a marker of stable
      microtubules, and reversed the okadaic acid-induced depression of growth
      associated protein-43, an axonal growth regulator. Thus, microtubule-stabilizing
      drugs show promise as new therapeutic agents for treating damaged microtubule
      networks characteristic of neurodegenerative disease.

PMID- 22594879
TI  - Long-term outcomes of add-on adefovir dipivoxil therapy to ongoing lamivudine in
      patients with lamivudine-resistant chronic hepatitis B.
AB  - AIM:   Add-on adefovir dipivoxil (ADV) therapy has been a standard rescue
      treatment for patients with lamivudine (LAM)-resistant chronic hepatitis B, but
      the overall benefits of long-term add-on ADV therapy are still limited. The aim
      of this study was to evaluate the long-term efficiency of add-on ADV treatment
      and to explore predictive factors associated with it. METHODS:   A total of 158
      patients with LAM-resistant chronic hepatitis B were included in this
      retrospective, multicenter, nationwide study in Japan. After confirming LAM
      resistance, ADV was added to LAM treatment. Three types of events were considered
      as outcomes: virological response, hepatitis B e antigen (HBeAg) clearance and
      alanine aminotransferase (ALT) normalization. Virological response was defined as
      serum hepatitis B virus (HBV) DNA levels of less than 3 log copies/mL. Baseline
      factors contributing to these outcomes were examined by univariate and
      multivariate analyses. RESULTS:   The median total duration of ADV treatment was
      41 months (range, 6-84). The rate of virological response was 90.8% at 4 years of
      treatment; HBeAg clearance and ALT normalization were achieved by 34.0% and
      82.7%, respectively, at the end of follow up. Each outcome had different
      predictive factors: baseline HBV DNA and albumin level were predictive factors
      for virological response, history of interferon therapy and ALT level for HBeAg
      clearance, and sex and baseline albumin level for ALT normalization. CONCLUSION: 
      Long-term add-on ADV treatment was highly effective in LAM-resistant chronic
      hepatitis B patients in terms of virological and biochemical responses. Lower HBV
      replication and lower albumin level at baseline led to better outcomes.

PMID- 22594881
TI  - Group 13 beta-ketoiminate compounds: gallium hydride derivatives as molecular
      precursors to thin films of Ga2O3.
AB  - Bis(beta-ketoimine) ligands, [R{N(H)C(Me)-CHC(Me)?O}(2)] (L(1)H(2), R =
      (CH(2))(2); L(2)H(2), R = (CH(2))(3)), linked by ethylene (L(1)) and propylene
      (L(2)) bridges have been used to form aluminum, gallium, and indium chloride
      complexes [Al(L(1))Cl] (3), [Ga(L(n))Cl] (4, n = 1; 6, n = 2) and [In(L(n))Cl]
      (5, n = 1; 7, n = 2). Ligand L(1) has also been used to form a gallium hydride
      derivative [Ga(L(1))H] (8), but indium analogues could not be made. beta
      ketoimine ligands, [Me(2)N(CH(2))(3)N(H)C(R')-CHC(R')?O] (L(3)H, R' = Me; L(4)H,
      R' = Ph), with a donor-functionalized Lewis base have also been synthesized and
      used to form gallium and indium alkyl complexes, [Ga(L(3))Me(2)] (9) and
      [In(L(3))Me(2)] (10), which were isolated as oils. The related gallium hydride
      complexes, [Ga(L(n))H(2)] (11, n = 3; 12, n = 4), were also prepared, but again
      no indium hydride species could be made. The complexes were characterized mainly
      by NMR spectroscopy, mass spectrometry, and single crystal X-ray diffraction. The
      beta-ketoiminate gallium hydride compounds (8 and 11) have been used as single
      source precursors for the deposition of Ga(2)O(3) by aerosol-assisted (AA)CVD
      with toluene as the solvent. The quality of the films varied according to the
      precursor used, with the complex [Ga(L(1))H] (8) giving by far the best quality
      films. Although the films were amorphous as deposited, they could be annealed at
      1000  degrees C to form crystalline Ga(2)O(3). The films were analyzed by powder
      XRD, SEM, and EDX.

PMID- 22594880
TI  - HIV+ women's narratives of non-disclosure: resisting the label of immorality.
AB  - Increasing partner disclosure rates among HIV+ individuals is widely seen as an
      important public health strategy to reduce HIV transmission. One approach for
      encouraging disclosure is to emphasise individuals' moral responsibility to
      disclose their status to their partners. We use South Africa as a case study to
      draw attention to two problems with labelling non-disclosure as immoral. First,
      we argue that because women are tested for HIV at much higher rates than men, any
      approach that involves blaming HIV+ individuals for not disclosing their status
      will disproportionately burden women. Second, through the narratives of six HIV+
      women, we highlight how a focus on morality undervalues the complexity of sexual
      partnerships. Specifically, women describe how their perceived obligation to
      disclose their status is directly influenced by communication with their sexual
      partners. Women also discuss how the onset of different life events might alter
      the meaning of HIV and change obligations regarding disclosure within the
      partnership. The differences in testing rates across gender combined with the
      complexity of sexual partnerships leads us to suggest that labelling non
      disclosure as immoral does little to advance HIV prevention. There is an urgent
      need to identify alternative interventions that support women through the
      disclosure process.

PMID- 22594882
TI  - Contrasting patterns of selection acting on MHC class I and class II DRB genes in
      the Alpine marmot (Marmota marmota).
AB  - The major histocompatibility complex (MHC) genes code for proteins that play a
      critical role in the immune system response. The MHC genes are among the most
      polymorphic genes in vertebrates, presumably due to balancing selection. The two
      MHC classes appear to differ in the rate of evolution, but the reasons for this
      variation are not well understood. Here, we investigate the level of polymorphism
      and the evolution of sequences that code for the peptide-binding regions of MHC
      class I and class II DRB genes in the Alpine marmot (Marmota marmota). We found
      evidence for four expressed MHC class I loci and two expressed MHC class II loci.
      MHC genes in marmots were characterized by low polymorphism, as one to eight
      alleles per putative locus were detected in 38 individuals from three French Alps
      populations. The generally limited degree of polymorphism, which was more
      pronounced in class I genes, is likely due to bottleneck the populations
      undergone. Additionally, gene duplication within each class might have
      compensated for the loss of polymorphism at particular loci. The two gene classes
      showed different patterns of evolution. The most polymorphic of the putative
      loci, Mama-DRB1, showed clear evidence of historical positive selection for amino
      acid replacements. However, no signal of positive selection was evident in the
      MHC class I genes. These contrasting patterns of sequence evolution may reflect
      differences in selection pressures acting on class I and class II genes.

PMID- 22594883
TI  - Estimating hydrogen cyanide in forage sorghum ( Sorghum bicolor ) by near
      infrared spectroscopy.
AB  - Hydrogen cyanide (HCN) is a toxic chemical that can potentially cause mild to
      severe reactions in animals when grazing forage sorghum. Developing technologies
      to monitor the level of HCN in the growing crop would benefit graziers, so that
      they can move cattle into paddocks with acceptable levels of HCN. In this study,
      we developed near-infrared spectroscopy (NIRS) calibrations to estimate HCN in
      forage sorghum and hay. The full spectral NIRS range (400-2498 nm) was used as
      well as specific spectral ranges within the full spectral range, i.e., visible
      (400-750 nm), shortwave (800-1100 nm) and near-infrared (NIR) (1100-2498 nm).
      Using the full spectrum approach and partial least-squares (PLS), the calibration
      produced a coefficient of determination (R(2)) = 0.838 and standard error of
      cross-validation (SECV) = 0.040%, while the validation set had a R(2) = 0.824
      with a low standard error of prediction (SEP = 0.047%). When using a multiple
      linear regression (MLR) approach, the best model (NIR spectra) produced a R(2) =
      0.847 and standard error of calibration (SEC) = 0.050% and a R(2) = 0.829 and SEP
      = 0.057% for the validation set. The MLR models built from these spectral regions
      all used nine wavelengths. Two specific wavelengths 2034 and 2458 nm were of
      interest, with the former associated with C?O carbonyl stretch and the latter
      associated with C-N-C stretching. The most accurate PLS and MLR models produced a
      ratio of standard error of prediction to standard deviation of 3.4 and 3.0,
      respectively, suggesting that the calibrations could be used for screening
      breeding material. The results indicated that it should be feasible to develop
      calibrations using PLS or MLR models for a number of users, including breeding
      programs to screen for genotypes with low HCN, as well as graziers to monitor
      crop status to help with grazing efficiency.

PMID- 22594886
TI  - Chemoselective organocatalytic aerobic oxidation of primary amines to secondary
      imines.
AB  - Biomimetic aerobic oxidation of primary benzylic amines has been achieved by
      using a quinone catalyst. Excellent selectivity is observed for primary,
      unbranched benzylic amines relative to secondary/tertiary amines, branched
      benzylic amines, and aliphatic amines. The exquisite selectivity for benzylic
      amines enables oxidative self-sorting within dynamic mixtures of amines and
      imines to afford high yields of cross-coupled imine products.

PMID- 22594884
TI  - Multilevel mediation analysis: The effects of omitted variables in the 1-1-1
      model.
AB  - Multilevel mediation analysis examines the indirect effect of an independent
      variable on an outcome achieved by targeting and changing an intervening variable
      in clustered data. We study analytically and through simulation the effects of an
      omitted variable at level 2 on a 1-1-1 mediation model for a randomized
      experiment conducted within clusters in which the treatment, mediator, and
      outcome are all measured at level 1. When the residuals in the equations for the
      mediator and the outcome variables are fully orthogonal, the two methods of
      calculating the indirect effect (ab, c - c') are equivalent at the between- and
      within-cluster levels. Omitting a variable at level 2 changes the interpretation
      of the indirect effect and will induce correlations between the random intercepts
      or random slopes. The equality of within-cluster ab and c - c' no longer holds.
      Correlation between random slopes implies that the within-cluster indirect effect
      is conditional, interpretable at the grand mean level of the omitted variable.

PMID- 22594887
TI  - Defects in CD54 and CD86 up-regulation by plasmacytoid dendritic cells during
      pregnancy.
AB  - Physiological modulation of the immune system is required for foetal tolerance
      during pregnancy. However, this immune regulation might lead to impaired self
      defence against pathogens. Indeed, pregnant women are more susceptible to newly
      encountered viruses comparing to non-pregnant women, as exemplified by the
      prevalence of severe complications in pregnant women infected with the pandemic
      influenza virus in 2009. Plasmacytoid dendritic cells (pDCs) are specialized
      dendritic cells that recognise viral antigens and initiate both innate and
      adaptive immune responses. We therefore sought to determine whether the number
      and/or the functions of peripheral blood pDCs are regulated during pregnancy. pDC
      maturation and interferon (IFN)-alpha production were analysed in response to
      Toll-like receptor (TLR) stimulation of peripheral blood mononuclear cells from
      pregnant and non-pregnant women. Our results reveal that pDC frequency is
      slightly decreased, while the IFN-alpha production in response to TLR stimulation
      increases during pregnancy. Interestingly, the up-regulation of the co
      stimulatory receptors CD54 (ICAM1) and CD86 is significantly decreased in pDCs
      from pregnant women as compared to controls, suggesting a possible impact on T
      cell responses. In conclusion, we propose that the modulation of CD54 and CD86
      expression on peripheral blood pDCs during pregnancy might decrease the
      initiation of adaptive antiviral immune responses.

PMID- 22594888
TI  - IDH mutations: new genetic signatures in cholangiocarcinoma and therapeutic
      implications.

PMID- 22594889
TI  - The roadmap of TRAIL apoptotic pathway-targeted cancer therapies: What is next?

PMID- 22594891
TI  - Cetuximab in metastatic colorectal cancer.
AB  - Management of metastatic colorectal cancer has evolved in the last 10 years, with
      the availability of targeted therapies resulting in improvement in quality of
      life and overall survival. Cetuximab is a chimeric monoclonal antibody that binds
      to the EGF receptor, and the net effects are inhibition of tumor growth,
      invasion, angiogenesis and metastasis. Cetuximab binding to the EGF receptor is
      also known to augment the effects of chemotherapy and radiotherapy. Only tumors
      expressing wild-type KRAS respond to cetuximab and improvements in progression
      free survival and overall survival are seen, whereas patients with mutant KRAS
      are considered to be resistant. Cetuximab is currently available worldwide for
      use as monotherapy or in combination with chemotherapy in first-, second- or
      third-line settings in metastatic colorectal cancer patients with wild-type KRAS.

PMID- 22594892
TI  - Bevacizumab: overview of the literature.
AB  - Inhibiting the angiogenic process is a clever method of cancer care. Over the
      last decade, some antiangiogenic compounds have been developed and approved for
      cancer treatment. Bevacizumab is a humanized monoclonal antibody that inhibits
      VEGF activity. When used in combination with chemotherapy, it has an important
      role for treating many types of advanced cancer, including colorectal cancer,
      renal cell carcinoma, non-small-cell lung cancer, breast cancer, ovarian cancer
      and glioblastoma multiforme. In this paper we review the basic science behind
      this molecule's development, as well the major clinical trials in which
      bevacizumab was involved in oncology.

PMID- 22594893
TI  - Retinoblastoma protein determines aggressiveness in triple-negative breast
      cancer.
AB  - Retinoblastoma protein (RB) is one of the most important tumor suppressors and
      functions in multiple biological pathways that are deregulated during tumor
      initiation and progression. Epithelial-to-mesenchymal transition (EMT) is a
      reversible embryonic process by which epithelial cells lose cell-cell contact and
      polarity, and its aberrant activation can trigger tumor progression and
      metastasis. Previously, it has been shown that depletion of RB initiates EMT by
      downregulating the adhesion molecule E-cadherin. The evaluated article suggests
      that RB inactivation contributes to loss of cell cycle control and also leads to
      downregulation of the miR-200 family, thereby causing upregulation of ZEB
      expression and consequently EMT by downregulation of E-cadherin. RB inactivation
      could be a key event underlying the mesenchymal and aggressive phenotype of
      triple-negative breast cancer. Furthermore, exploring links between RB
      inactivation and EMT might reveal new therapeutic targets for triple-negative
      breast cancer.

PMID- 22594896
TI  - Improving triage and management of patients with skin cancer: challenges and
      considerations for the future.
AB  - Skin cancer is the most common malignancy in humans, thus representing a major
      health concern. Because of the increasing attention to skin cancer prevention,
      there has been a growing workload for dermatology clinics, with patients referred
      from primary care requiring assessment of suspicious skin tumors. This places a
      strain on limited specialist resources and can create a paradoxical situation
      wherein an early diagnosis becomes increasingly difficult for those patients who
      actually do suffer from skin cancer. The aim of these recommendations is to
      propose an updated, rational system of triage, involving improved accuracy of
      diagnosis and more timely management of skin cancer by both general practitioners
      and dermatologists.

PMID- 22594894
TI  - New vitamin D analogs as potential therapeutics in melanoma.
AB  - Extensive evidence shows that the active form of vitamin D3--1alpha,25
      dihydroxyvitamin D3--plays an important role in cancer prevention, has
      tumorostatic activity and may potentially be used in therapy for melanoma.
      Vitamin D3 and its analogs (secosteroids) exert multiple effects on cancer cells,
      including inhibition of cell growth and induction of differentiation. Activity of
      secosteroids depends on multiple cellular factors, including expression of the
      vitamin D receptor. Despite its endogenous origin, the key drawback for the use
      of pharmacologically effective doses of 1alpha,25-dihydroxyvitamin D3 is its
      hypercalcemic effect leading to profound toxicity. The solution may lie in
      properties of vitamin D3 analogs with modified side chains, which demonstrate low
      calcemic activity but conserve the anti-tumor properties. Noncalcemic vitamin D
      compounds were found to be potent in multiple studies that mandate further
      clinical testing. Finally, recent studies revealed alternative metabolic pathways
      for secosteroids and new targets in the cells, which opens up new therapeutic
      possibilities.

PMID- 22594895
TI  - Molecular targets in melanoma: time for 'ethnic personalization'.
AB  - Worldwide, the incidence of melanoma continues to rise. Although not the most
      common cutaneous malignancy, it is the most lethal. Until recently, while other
      oncologic patients benefited from the nuances of targeted therapy, those
      afflicted with melanoma lacked that option. In 2011, the US FDA approved an oral
      agent that targets the BRAF oncogene. As this information is promising, it is
      essential that other populations (in addition to Caucasians) are examined, in
      order to further comprehend the biology of melanoma. Recent studies profiling
      various ethnicities, including Asians, have provided novel data with respect to
      the molecular characterization (c-KIT, BRAF, NRAS) of melanoma. It is hopeful
      that the management of melanoma will be universally applicable to all ethnic
      groups.

PMID- 22594897
TI  - Pathogenesis and management of primary CNS lymphoma.
AB  - Primary CNS lymphoma (PCNSL), a rare variant of extranodal non-Hodgkin's
      lymphoma, may cause various neurological symptoms and signs. The best therapeutic
      strategy is still a matter of debate. High-dose methotrexate (HD-MTX) is the most
      active compound and should be used as the backbone for any chemotherapy applied.
      Several other chemotherapeutic drugs have been assessed in combination with HD
      MTX, but no standard has yet been defined. Whole-brain radiotherapy is active
      against PCNSL, but typically does not confer long-lasting remission and is
      associated with significant neurotoxicity in many patients. The recently
      published G-PCNSL-SG1 trial has shown that consolidating whole-brain radiotherapy
      after HD-MTX-based chemotherapy does not prolong overall survival and may
      therefore be deferred. Combined systemic and intraventricular polychemotherapy,
      or high-dose chemotherapy followed by stem cell transplantation may offer cures
      to younger patients. Improving treatment regimens without adding significant
      (neuro-)toxicity should be the focus of ongoing and future studies.

PMID- 22594898
TI  - Molecular mechanisms of temozolomide resistance in glioblastoma multiforme.
AB  - Glioblastoma multiforme (GBM; WHO astrocytoma grade IV) is considered incurable
      owing to its inherently profound resistance towards current standards of therapy.
      Considerable effort is being devoted to identifying the molecular basis of
      temozolomide resistance in GBMs and exploring novel therapeutic regimens that may
      improve overall survival. Several independent DNA repair mechanisms that normally
      safeguard genome integrity can facilitate drug resistance and cancer cell
      survival by removing chemotherapy-induced DNA adducts. Furthermore,
      subpopulations of cancer stem-like cells have been implicated in the treatment
      resistance of several malignancies including GBMs. Thus, a growing number of
      molecular mechanisms contributing to temozolomide resistance are being uncovered
      in preclinical studies and, consequently, we are being presented with a broad
      range of potentially novel targets for therapy. A substantial future challenge is
      to successfully exploit the increasing molecular knowledge contributing to
      temozolomide resistance in robust clinical trials and to ultimately improve
      overall survival for GBM patients.

PMID- 22594899
TI  - Antiangiogenic therapies in glioblastoma multiforme.
AB  - Glioblastoma multiforme (GBM) is the most common and lethal of adult gliomas. The
      prognosis for the great majority of patients with GBM is poor as almost all
      tumors recur following optimal surgical resection, radiation and standard
      chemotherapy, resulting in rapid disease-related death. The standard of care for
      recurrent GBM has not been clearly established. GBMs are highly vascularized
      brain tumors and growth has been shown to be angiogenesis dependent, thus
      stimulating interest in developing antiangiogenic therapeutic strategies.
      Antiangiogenic agents are the most promising novel agents in development for GBM
      but to date have not substantially changed overall survival. Future
      antiangiogenic strategies designed to overcome limitations of current
      antiangiogenic agents will likely involve the use of agent combinations that
      target pathways mediating resistance to antiangiogenic agents and tumor invasion.

PMID- 22594900
TI  - Cognitive function testing in adult brain tumor trials: lessons from a
      comprehensive review.
AB  - Neurocognitive function (NCF) impairment is an important component of primary and
      metastatic brain tumors and their therapeutic interventions. As a result, modern
      clinical trials of cranial irradiation for adult cancer patients have
      incorporated NCF testing as a primary or secondary end point. In doing so, these
      clinical trials have provided a novel insight into our understanding of the NCF
      effects of cranial irradiation and brain tumor progression. In this article, we
      review these clinical trials both in terms of the trial findings and in terms of
      the types of NCF tests used in these trials. We also provide an introduction to
      the strengths and limitations of these NCF tests, as well as expert commentary on
      the current status and future directions of NCF testing in brain tumor trials.

PMID- 22594901
TI  - Radiotherapy-induced hypopituitarism: a review.
AB  - Hypopituitarism is a disorder caused by impaired hormonal secretions from the
      hypothalamic-pituitary axis. Radiotherapy is the most common cause of iatrogenic
      hypopituitarism. The hypothalamic-pituitary axis inadvertently gets irradiated in
      patients receiving prophylactic cranial radiotherapy for leukemia, total body
      irradiation and radiotherapy for intracranial, base skull, sinonasal and
      nasopharyngeal tumors. Radiation-induced hypopituitarism (RIH) is insidious,
      progressive and largely nonreversible. Mostly, RIH involves one hypothalamic
      pituitary axis; however, multiple hormonal axes deficiency starts developing at
      higher doses. Although the clinical effects of the hypopituitarism are more
      profound in children and young adults, its implications in older adults are being
      increasingly recognized. The risk continues to persist or increase up to 10 years
      following radiation exposure. The clinical management of hypopituitarism is
      challenging both for the patients and healthcare providers. Here we have reviewed
      the scale of the problem, the risk factors and the management of RIH.

PMID- 22594902
TI  - Chemotherapy and targeted agents for thymic malignancies.
AB  - Thymic malignancies are rare epithelial tumors that may be aggressive and
      difficult to treat. Thymomas are usually localized to the anterior mediastinum
      and are frequently eligible for upfront surgical resection. However, nearly 30%
      of patients present with locally advanced tumors at time of diagnosis, and
      chemotherapy is then used to reduce the tumor burden, possibly allowing
      subsequent surgery and/or radiotherapy. Metastatic and recurrent thymic
      malignancies may similarly be treated with chemotherapy. More recently, the
      molecular characterization of thymoma and thymic carcinoma led to the
      identification of potentially druggable targets, laying the foundations to
      implement personalized medicine for patients.

PMID- 22594904
TI  - Aqueous multiphase systems of polymers and surfactants provide self-assembling
      step-gradients in density.
AB  - This Communication demonstrates the generation of over 300 phase-separated
      systems-ranging from two to six phases-from mixtures of aqueous solutions of
      polymers and surfactants. These aqueous multiphase systems (MuPSs) form self
      assembling, thermodynamically stable step-gradients in density using a common
      solvent, water. The steps in density between phases of a MuPS can be very small
      (Deltarho ~ 0.001 g/cm(3)), do not change over time, and can be tuned by the
      addition of co-solutes. We use two sets of similar objects, glass beads and
      pellets of different formulations of Nylon, to demonstrate the ability of MuPSs
      to separate mixtures of objects by differences in density. The stable interfaces
      between phases facilitate the convenient collection of species after separation.
      These results suggest that the stable, sharp step-gradients in density provided
      by MuPSs can enable new classes of fractionations and separations based on
      density.

PMID- 22594905
TI  - Additive effects of ulinastatin and docetaxel on growth of breast cancer
      xenograft in nude mice and expression of PGE2, IL-10, and IL-2 in primary breast
      cancer cells.
AB  - Ulinastatin is a broad-spectrum enzyme inhibitor extracted from urine. Previous
      data from our group suggested that ulinastatin could significantly inhibit
      proliferation of human breast MDA-MB-231 cells, growth of tumor xenograft in nude
      mice, and expression of interleukin (IL)-6 and IL-8. In the present study, we
      investigated whether there is an additive effect of ulinastatin and docetaxel on
      growth of breast cancer xenografts in nude mice and its possible mechanisms. Nude
      mice and primary human breast cancer cells were treated with phosphate buffered
      saline (PBS), ulinastatin, docetaxel, or ulinastatin plus docetaxel,
      respectively. Their effects on xenograft growth; expressions of cyclooxygenase-2
      (COX2), prostaglandin E2 receptor 2 (EP2), IL-10, and IL-2; and secretion of
      prostaglandin E2 (PGE2) were examined using variety of methods, including semi
      quantitative reverse transcription-polymerase chain reaction (RT-PCR), Western
      blot, enzyme-linked immunosorbent (ELISA) assay, and immunohistochemistry SP
      method. The treatment with ulinastatin, docetaxel, or ulinastatin plus docetaxel
      could significantly (1) inhibit COX2 and IL-10 expression in primary tumor cells
      at both mRNA and protein levels, (2) reduce PGE2 secretion in culture supernatant
      (p<0.05), (3) inhibit COX2, EP2, and IL-10 protein levels in primary xenograft of
      nude mice, and (4) increase IL-2 expression (p<0.05) in primary xenografts of
      nude mice. In addition, ulinastatin and docetaxel had additive effects. We
      suggest that ulinastatin had similar effects of docetaxel and can enhance
      docetaxel's anticancer effects possibly by inhibiting COX2 expression, reducing
      PGE2 and EP2 expression and their binding, upregulating IL-2, and downregulating
      IL-10.

PMID- 22594906
TI  - Nafion-zirconium phosphate composite membrane: a new approach to prepare (32)P
      patches for superficial brachytherapy applications.
AB  - This article describes a method for the preparation of (32)P patch for the
      treatment of skin cancer. It is based on the surface modification of a Nafion
      film by treatment with ZrOCl(2) solution, impregnation of a predicted quantity of
      (32)P into the film, and its subsequent immobilization into a nonleachable matrix
      by lamination. The effect of variations of critical parameters on the
      incorporation of (32)P into the membrane, such as solution pH, contact time,
      reaction volume, inactive carrier concentration of the feed, reaction
      temperature, and so on, was investigated to arrive at the conditions resulting in
      optimum retention of (32)P activity. The morphology of the membrane was evaluated
      by scanning electron microscope and energy dispersive spectral analyses. Quality
      control tests were carried out to ensure nonleachability, uniform distribution of
      activity, and stability of the patches.

PMID- 22594908
TI  - Ocular toxoplasmosis I: parasitology, epidemiology and public health.
AB  - Ocular toxoplasmosis results from retinal infection with the protozoan,
      Toxoplasma gondii. This parasite, which exists as multiple clonal subpopulations
      and in three stages, is capable of replication in any nucleated cell of its
      primary feline or multiple paratenic hosts. Human seroprevalence of toxoplasmosis
      is high across the globe, but with geographic variation. While prevalence of
      ocular toxoplasmosis is not well documented, toxoplasmic retinochoroiditis is the
      commonest form of posterior uveitis in many countries. Correlation of parasite
      genotype with disease is an important area of new research. Ocular infection with
      T. gondii often follows ingestion of bradyzoites in undercooked infected meat.
      Oocysts may survive for an extended period in the environment, and water
      contaminated with oocysts is an important source in toxoplasmosis epidemics.
      Ocular toxoplasmosis is preventable by a combination of community activities and
      personal measures. Public health action is well justified by the considerable
      burden of congenital and postnatal infections.

PMID- 22594909
TI  - Goodbye, Columbus.

PMID- 22594907
TI  - Progress report on the first sub-Saharan Africa trial of newer versus older
      antihypertensive drugs in native black patients.
AB  - BACKGROUND: The epidemic surge in hypertension in sub-Saharan Africa is not
      matched by clinical trials of antihypertensive agents in Black patients recruited
      in this area of the world. We mounted the Newer versus Older Antihypertensive
      agents in African Hypertensive patients (NOAAH) trial to compare, in native
      African patients, a single-pill combination of newer drugs, not involving a
      diuretic, with a combination of older drugs including a diuretic. METHODS:
      Patients aged 30 to 69 years with uncomplicated hypertension (140 to 179/90 to
      109 mmHg) and <=2 associated risk factors are eligible. After a four week run-in
      period off treatment, 180 patients have to be randomized to once daily
      bisoprolol/hydrochlorothiazide 5/6.25 mg (R) or amlodipine/valsartan 5/160 mg
      (E). To attain blood pressure <140/<90 mmHg during six months, the doses of
      bisoprolol and amlodipine should be increased to 10 mg/day with the possible
      addition of up to 2 g/day alpha-methyldopa. RESULTS: At the time of writing of
      this progress report, of 206 patients enrolled in the run-in period, 140 had been
      randomized. At randomization, the R and E groups were similar (P >= 0.11) with
      respect to mean age (50.7 years), body mass index (28.2 kg/m(2)), blood pressure
      (153.9/91.5 mmHg) and the proportions of women (53.6%) and treatment naive
      patients (72.7%). After randomization, in the R and E groups combined, blood
      pressure dropped by 18.2/10.1 mmHg, 19.4/11.2 mmHg, 22.4/12.2 mmHg and 25.8/15.2
      mmHg at weeks two (n = 122), four (n = 109), eight (n = 57), and 12 (n = 49),
      respectively. The control rate was >65% already at two weeks. At 12 weeks, 12
      patients (24.5%) had progressed to the higher dose of R or E and/or had alpha
      methyldopa added. Cohort analyses of 49 patients up to 12 weeks were
      confirmatory. Only two patients dropped out of the study. CONCLUSIONS: NOAAH
      (NCT01030458) demonstrated that blood pressure control can be achieved fast in
      Black patients born and living in Africa with a simple regimen consisting of a
      single-pill combination of two antihypertensive agents. NOAAH proves that
      randomized clinical trials of cardiovascular drugs in the indigenous populations
      of sub-Saharan Africa are feasible.

PMID- 22594910
TI  - Angiolymphoid hyperplasia with eosinophilia in infancy.

PMID- 22594911
TI  - Workflows for microarray data processing in the Kepler environment.
AB  - BACKGROUND: Microarray data analysis has been the subject of extensive and
      ongoing pipeline development due to its complexity, the availability of several
      options at each analysis step, and the development of new analysis demands,
      including integration with new data sources. Bioinformatics pipelines are usually
      custom built for different applications, making them typically difficult to
      modify, extend and repurpose. Scientific workflow systems are intended to address
      these issues by providing general-purpose frameworks in which to develop and
      execute such pipelines. The Kepler workflow environment is a well-established
      system under continual development that is employed in several areas of
      scientific research. Kepler provides a flexible graphical interface, featuring
      clear display of parameter values, for design and modification of workflows. It
      has capabilities for developing novel computational components in the R, Python,
      and Java programming languages, all of which are widely used for bioinformatics
      algorithm development, along with capabilities for invoking external applications
      and using web services. RESULTS: We developed a series of fully functional
      bioinformatics pipelines addressing common tasks in microarray processing in the
      Kepler workflow environment. These pipelines consist of a set of tools for GFF
      file processing of NimbleGen chromatin immunoprecipitation on microarray (ChIP
      chip) datasets and more comprehensive workflows for Affymetrix gene expression
      microarray bioinformatics and basic primer design for PCR experiments, which are
      often used to validate microarray results. Although functional in themselves,
      these workflows can be easily customized, extended, or repurposed to match the
      needs of specific projects and are designed to be a toolkit and starting point
      for specific applications. These workflows illustrate a workflow programming
      paradigm focusing on local resources (programs and data) and therefore are close
      to traditional shell scripting or R/BioConductor scripting approaches to pipeline
      design. Finally, we suggest that microarray data processing task workflows may
      provide a basis for future example-based comparison of different workflow
      systems. CONCLUSIONS: We provide a set of tools and complete workflows for
      microarray data analysis in the Kepler environment, which has the advantages of
      offering graphical, clear display of conceptual steps and parameters and the
      ability to easily integrate other resources such as remote data and web services.

PMID- 22594913
TI  - Mass spectrometric identification of silver nanoparticles: the case of
      Ag32(SG)19.
AB  - Mass spectrometry has played a key role in identifying the members of a series of
      gold clusters, which has enabled the development of magic-number cluster theory.
      The successes of the gold cluster system have yet to be repeated in another metal
      cluster system, however. Silver clusters in particular have proven to be
      challenging due to their relative instability compared with gold clusters. Using
      the well-characterized gold nanocluster, Au(25)(SG)(18), we present optimized
      electrospray ionization mass spectrometry (ESI-MS) instrumental parameters for
      the maximal transmission of the intact cluster. Parameters shown to have the
      largest effect on intact cluster transmission/detection include trap and transfer
      collision energy, source temperature, and cone gas flow rate. Herein we describe
      a general strategy to acquire mass spectra of fragile metal clusters with
      reliable mass assignments. By also optimizing sample solution conditions, high
      quality ESI mass spectra of a prototypical silver:glutathione (Ag:SG) cluster
      were obtained without significant fragmentation. By using gentle conditions and
      solution conditions designed to stabilize the clusters, fragmentation was
      dramatically reduced and mass spectra with isotopic resolution were measured.
      Using this strategy, we have made the first formula assignment for a ligand
      protected Ag cluster of Ag(32)(SG)(19).

PMID- 22594912
TI  - Interaction between interleukin-10 (IL-10) polymorphisms and dietary fibre in
      relation to risk of colorectal cancer in a Danish case-cohort study.
AB  - BACKGROUND: More than 50% of the colorectal cancer (CRC) etiology has been
      attributed to diet. Established or suspected dietary factors modifying risk of
      CRC are red meat, cereals, fish, and fibre. Diet and lifestyle may be linked to
      cancer through inflammation. Interleukin-10 (IL-10) is an anti-inflammatory
      cytokine. We wanted to test if dietary factors and IL10 polymorphisms interact in
      relation to colorectal carcinogenesis. METHODS: The functional IL10 polymorphism
      C-592A (rs1800872) and the marker rs3024505 were assessed in relation to diet and
      lifestyle in a nested case-cohort study of 378 CRC cases and 775 randomly
      selected participants from a prospective study of 57,053 persons. Genotyping data
      on the IL10 polymorphism C-592A, smoking and non-steroidal anti-inflammatory
      drugs (NSAID) was retrieved from Vogel et al. (Mutat Res, 2007; 624:88).
      Incidence rate ratios (IRR) and 95% Confidence Interval (95% CI) were calculated.
      RESULTS: No associations were found between the IL10 rs3024505 polymorphism and
      risk of CRC. There was interaction between rs3024505 and dietary fibre (P-value
      for interaction = 0.01). IL10 rs3024505 homozygous wildtype carriers were at 27%
      reduced risk of CRC per 10 g fibre per day (95% CI: 0.60-0.88) whereas variant
      carriers had no risk reduction by fibre intake. Also, interaction between IL10 C
      592A and intake of fibre was found (P-value for interaction = 0.02). Among those
      eating <17.0 grams of fibre per day, carriers of an C-592A variant allele had a
      statistically significantly higher risk of colorectal cancer compared to
      homozygous wildtypes. No significant differences in colorectal cancer risk were
      observed between the reference group (CC and <17.0 g/day) and carriers of one C
      592A variant allele eating 17.0 or more grams of dietary fibre per day. This
      suggests that the increased risk due to carrying the variant allele can be
      overcome by higher fibre intake. No interactions between IL10 polymorphisms and
      dietary meat, cereal, or fish intake, or between IL10 rs3024505 and smoking or
      NSAID use were found. CONCLUSIONS: In this northern Caucasian cohort we found
      interaction between IL10 and dietary fibre in CRC carcinogenesis. High intake of
      fibre seems to protect against CRC among individuals with IL10 related genetic
      susceptibility to CRC. This finding should be evaluated in other prospective and
      population-based cohorts with different ethnic groups.

PMID- 22594915
TI  - Deconstructing 'barriers' to access: minority ethnic women and medicalised
      maternal health services in Vietnam.
AB  - Low maternal health service utilisation amongst minority ethnic women in Vietnam
      is often attributed to 'traditional customs'. Drawing on secondary data and
      original, qualitative research amongst Hmong and Thai communities, this paper
      analyses minority behaviour related to childbirth. The informed selectivity in
      service attendance identified can be considered, in part, a rejection of current
      medicalised approaches at health facilities, where supine delivery is compulsory
      and family members are prohibited from attending women in labour. The paper
      reveals how conventional analyses of barriers to minority maternal health service
      utilisation inhibit scrutiny of the ways services fail to engage with or
      accommodate local preferences. Participatory identification of mutually
      acceptable delivery methods by maternal health staff and local women is
      recommended to enable the development of culturally inclusive services.

PMID- 22594914
TI  - Touching and feeling: differences in pleasant touch processing between glabrous
      and hairy skin in humans.
AB  - Previous functional magnetic resonance imaging studies in two rare patients,
      together with microneurography and psychophysical observations in healthy
      subjects, have demonstrated a system of mechanosensitive C-fiber tactile (CT)
      afferents sensitive to slowly moving stimuli. They project to the posterior
      insular cortex and signal pleasant aspects of touch. Importantly, CTs have not
      been found in the glabrous skin of the hand, yet it is commonly observed that
      glabrous skin touch is also perceived as pleasant. Here we asked if the brain
      processing of pleasant touch differs between hairy and glabrous skin by stroking
      the forearm and glabrous skin of the hand during positron emission tomography.
      The data showed that, when contrasting slow brush stroking on the forearm with
      slow brush stroking on the palm, there were significant activations of the
      posterior insular cortex and mid-anterior orbitofrontal cortex. The opposite
      contrast showed a significant activation of the somatosensory cortices. Although
      concurrent psychophysical ratings showed no differences in intensity or
      pleasantness ratings, a subsequent touch questionnaire in which subjects used a
      newly developed 'touch perception task' showed significant difference for the two
      body sites. Emotional descriptors received higher ratings on the forearm and
      sensory descriptors were rated more highly on the palm. The present findings are
      consistent with the hypothesis that pleasant touch from hairy skin, mediated by
      CT afferents, is processed in the limbic-related cortex and represents an innate
      non-learned process. In contrast, pleasant touch from glabrous skin, mediated by
      A-beta afferents, is processed in the somatosensory cortex and represents an
      analytical process dependent on previous tactile experiences.

PMID- 22594916
TI  - HLA-haploidentical transplantations for primary immunodeficiencies: a single
      center experience.
AB  - SCID is characterized by profound deficiencies of T and B lymphocytes. HSCT is
      the only curative treatment for children with SCID. The clinical characteristics
      and outcome of 30 HLA-haploidentical transplantations in 18 patients (15 SCID,
      two Omenn syndrome, and one MHC Class II deficiency) are reported here. The age
      of patients at diagnosis ranged from one and half to nine months (median: four
      months). The median time was one month between the diagnosis and the time of the
      initial transplantation. Infused CD34+ stem cell dose was ranged between 7 and
      94.2 * 10(6) /kg. Nine of 18 patients were found to be positive for CMV
      antigenemia at diagnosis; therefore, none of them received a conditioning
      regimen. The most common complication was graft failure (61%), so repeated
      transplantations (two to four) were performed in seven patients. The mean time of
      lymphoid engraftment was 17.5 days (median: 16, range: 11-29 days). Ten of 15
      SCID (67%) patients survived with a stable complete donor chimerism. However, all
      three non-SCID patients died. In conclusion, in the absence of a matched family
      donor, HLA-haploidentical transplantation from parental donors represents a
      readily available treatment option especially for patients with SCID, offering a
      high chance of cure.

PMID- 22594917
TI  - Leaf anatomical properties in relation to differences in mesophyll conductance to
      CO(2)  and photosynthesis in two related Mediterranean Abies species.
AB  - Abies alba and Abies pinsapo are closely related species with the same ribulose
      1.5-bisphosphate carboxylase/oxygenase (Rubisco) large subunit (rbcL) but
      contrasting hydraulic traits and mesophyll structure occurring in the Iberian
      Peninsula under contrasting conditions. As photosynthesis and hydraulic
      capacities often co-scale, we hypothesize that these species differ in mesophyll
      conductance to CO(2)  (g(m) ). g(m)  and key anatomical traits were measured in
      both species. Drought-adapted population of A. pinsapo has higher photosynthesis
      than the more mesic population of A. alba, in agreement with its higher hydraulic
      capacity. However, A. alba exhibits the largest stomatal conductance (g(s) ), and
      so water use efficiency (WUE) is much higher in A. pinsapo. The differences in
      photosynthesis were explained by differences in g(m) , indicating a correlation
      between hydraulic capacity and g(m) . We report a case where g(m)  is the main
      factor limiting photosynthesis in one species (A. alba) when compared with the
      other one (A. pinsapo). The results also highlight the discrepancy between g(m) 
      estimates based on anatomical measurements and those based on gas exchange
      methods, probably due to the very large resistance exerted by cell walls and the
      stroma in both species. Thus, the cell wall and chloroplast properties in
      relation to CO(2)  diffusion constitute a near-future research priority.

PMID- 22594918
TI  - Palladium-catalyzed substitution and cross-coupling of benzylic fluorides.
AB  - Benzylic fluorides are suitable substrates for Pd(0)-catalyzed Tsuji-Trost
      substitution using carbon, nitrogen, oxygen, and sulfur nucleophiles and for
      cross-coupling with phenylboronic acid. For the bifunctional substrate 4
      chlorobenzyl fluoride, fine-tuning of the reaction conditions allows for the
      regioselective displacement of either the chlorine or fluorine substituent. The
      leaving group ability of fluoride vs other groups displaced in substitution is
      CF(3)CO(2) ~ p-NO(2)C(6)H(4)CO(2) ~ OCO(2)CH(3) > F > CH(3)CO(2), a ranking
      similar to allylic fluorides under Pd catalysis.

PMID- 22594919
TI  - Nutrimetabolomic strategies to develop new biomarkers of intake and health
      effects.
AB  - Correctly assessing the metabolic status of subjects after consumption of
      specific diets is an important challenge for modern nutrition. Recently,
      metabolomics has been proposed as a powerful tool for exploring the complex
      relationship between nutrition and health. Nutritional metabolomics, through
      investigating the role that dietary components play in the maintenance of health
      and development of risk disease, aims to identify new biomarkers that allow the
      intake of these compounds to be monitored and related to their expected
      biological effects. This review offers an overview of the application of
      nutrimetabolomic strategies in the discovery of new biomarkers in human
      nutritional research, suggesting three main categories: (1) assessment of
      nutritional and dietary interventions; (2) diet exposure and food consumption
      monitoring; and (3) health phenotype and metabolic impact of diet. For this
      purpose, several examples of these applications will be used to provide evidence
      and to discuss the advantages and drawbacks of these nutrimetabolomic strategies.

PMID- 22594920
TI  - Mate choice among yeast gametes can purge deleterious mutations.
AB  - Meiosis in Saccharomyces yeast produces four haploid gametes that usually fuse
      with each other, an extreme form of self-fertilization among the products of a
      single meiosis known as automixis. The gametes signal to each other with sex
      pheromone. Better-quality gametes produce stronger signals and are preferred as
      mates. We suggest that the function of this signalling system is to enable mate
      choice among the four gametes from a single meiosis and so to promote the
      clearance of deleterious mutations. To support this claim, we construct a
      mathematical model that shows that signalling during automixis (i) improves the
      long-term fitness of a yeast colony and (ii) lowers its mutational load. We also
      show that the benefit to signalling is greater with larger numbers of segregating
      mutations.

PMID- 22594921
TI  - Loss of IL-10 decreases mouse postpubertal mammary gland development in the
      absence of inflammation.
AB  - IL-10 is a pleiotrophic anti-inflammatory cytokine. Decreased IL-10 expression is
      associated with an increased breast cancer risk but the mechanism is not clear.
      This study was designed to test the hypothesis that the loss of IL-10 alters
      mammary development, even in the absence of inflammation. Wild-type and IL-10-/-
      mouse littermates were similar in growth, development, and breeding success.
      Using whole-mounts and paraffin sections, mammary glands from pre-pubertal mice
      (d21) were found to not be affected by the IL-10 null genotype. However, after
      the onset of estrous cycling, ductal structure, but not lymph nodes or
      adipocytes, of IL-10 knockout mice were found to moderately decrease at day 55,
      80, and 150 of age. This phenotype was not rescued by lactogenesis. At day 2 of
      lactation, IL-10 null mice had reduced lobular complexity and glandular area with
      the retention of adipocytes. These results support the hypothesis that absence of
      IL-10 reduces glandular development during postnatal development, at maturity,
      and during the early stages of lactation. Although our study cannot distinguish
      between a direct IL-10 effect on the epithelial cells and an indirect systemic
      effect, epithelial cell responses to IL-10 should be considered in the
      therapeutic applications of cytokines or cytokine ablation.

PMID- 22594922
TI  - The indoleamine 2,3-dioxygenase inhibitor 1-methyl-tryptophan suppresses
      mitochondrial function, induces aerobic glycolysis and decreases interleukin-10
      production in human lymphocytes.
AB  - BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) suppresses adaptive immunity. It is
      known that IDO induces T-cell differentiation to regulatory T-cells (Treg)
      through tryptophan depletion and/or kynurenine pathway products. CD4+ effector T
      cells require distinct metabolic programs in order to support their function as
      compared to Treg cells. Furthermore, glucose metabolism is also known to affect B
      cell survival and function. The effect of IDO on glucose metabolism of
      lymphocytes was evaluated by using its inhibitor 1-methyl-DL-tryptophan (1-MT).
      METHODS: Ten healthy volunteers vaccinated against tetanus. Peripheral blood
      mononuclear cells (PBMC) were cultured with or without tetanus toxoid and/or 1
      MT. Cell proliferation was assessed by optical microscopy, glucose uptake by
      measuring its concentration in the supernatant, aerobic glycolysis by assessing
      lactate concentration in the supernatant, mitochondrial function by XTT assay,
      and finally production of Tregs' signature cytokine IL-10 by means of ELISA.
      RESULTS: Primarily, IDO decreases glucose uptake by stimulated lymphocytes.
      Secondly, IDO increases mitochondrial function in stimulated lymphocytes. In
      addition, IDO decreases aerobic glycolysis in stimulated lymphocytes. Finally,
      IDO induces the production of the immunosuppressive cytokine IL-10 by stimulated
      lymphocytes. CONCLUSION: Considering that cell metabolism plays a significant
      role in lymphocyte differentiation and function, IDO may exert its
      immunomodulatory effect by interfering with cell metabolism.

PMID- 22594924
TI  - Proliferative retinopathy in Duchenne muscular dystrophy and its response to
      bevacizumab.

PMID- 22594923
TI  - Urinary metabolic phenotyping the slc26a6 (chloride-oxalate exchanger) null mouse
      model.
AB  - The prevalence of renal stone disease is increasing, although it remains higher
      in men than in women when matched for age. While still somewhat controversial,
      several studies have reported an association between renal stone disease and
      hypertension, but this may be confounded by a shared link with obesity. However,
      independent of obesity, hyperoxaluria has been shown to be associated with
      hypertension in stone-formers, and the most common type of renal stone is
      composed of calcium oxalate. The chloride-oxalate exchanger slc26a6 (also known
      as CFEX or PAT-1), located in the renal proximal tubule, was originally thought
      to have an important role in sodium homeostasis and thereby blood pressure
      control, but it has recently been shown to have a key function in oxalate balance
      by mediating oxalate secretion in the gut. We have applied two orthogonal
      analytical platforms (NMR spectroscopy and capillary electrophoresis with UV
      detection) in parallel to characterize the urinary metabolic signatures related
      to the loss of the renal chloride-oxalate exchanger in slc26a6 null mice. Clear
      metabolic differentiation between the urinary profiles of the slc26a6 null and
      the wild type mice were observed using both methods, with the combination of NMR
      and CE-UV providing extensive coverage of the urinary metabolome. Key
      discriminating metabolites included oxalate, m-hydroxyphenylpropionylsulfate (m
      HPPS), trimethylamine-N-oxide, glycolate and scyllo-inositol (higher in slc26a6
      null mice) and hippurate, taurine, trimethylamine, and citrate (lower in slc26a6
      null mice). In addition to the reduced efficiency of anion transport, several of
      these metabolites (hippurate, m-HPPS, methylamines) reflect alteration in gut
      microbial cometabolic activities. Gender-related metabotypes were also observed
      in both wild type and slc26a6 null groups. Urinary metabolites that showed a sex
      specific pattern included trimethylamine, trimethylamine-N-oxide, citrate,
      spermidine, guanidinoacetate, and 2-oxoisocaproate. The gender-dependent
      metabolic expression of the consequences of slc26a6 deletion might have relevance
      to the difference in prevalence of renal stone formation in men and women. The
      different composition of microbial metabolites in the slc26a6 null mice is
      consistent with the fact that the slc26a6 transporter is found in a range of
      tissues, including the kidney and intestine, and provides further evidence for
      the "long reach" of the microbiota in physiological and pathological processes.

PMID- 22594925
TI  - Filling gaps in the series of noninnocent hetero-1,3-diene chelate ligands:
      ruthenium complexes of redox-active alpha-azocarbonyl and alpha-azothiocarbonyl
      ligands RNNC(R')E, E = O or S.
AB  - The series of 4-center unsaturated chelate ligands A?B-C?D with redox activity to
      yield (-)A-B?C-D(-) in two steps has been complemented by two new combinations
      RNNC(R')E, E = O or S, R = R' = Ph. The ligands N-benzoyl-N'-phenyldiazene =
      L(O), and N-thiobenzoyl-N'-phenyldiazene = L(S), (obtained in situ) form
      structurally characterized compounds [(acac)(2)Ru(L)], 1 with L = L(O), and 3
      with L = L(S), and [(bpy)(2)Ru(L)](PF(6)), 2(PF(6)) with L = L(O), and 4(PF(6))
      with L = L(S) (acac(-) = 2,4-pentanedionato; bpy = 2,2'-bipyridine). According to
      spectroscopy and the N-N distances around 1.35 A and N-C bond lengths of about
      1.33 A, all complexes involve the monoanionic (radical) ligand form. For 1 and 3,
      the antiferromagnetic spin-spin coupling with electron transfer-generated Ru(III)
      leads to diamagnetic ground states of the neutral complexes, whereas the cations
      2(+) and 4(+) are EPR-active radical ligand complexes of Ru(II). The complexes
      are reduced and oxidized in reversible one-electron steps. Electron paramagnetic
      resonance (EPR) and UV-vis-NIR spectroelectrochemistry in conjunction with time
      dependent density functional theory (TD-DFT) calculations allowed us to assign
      the electronic transitions in the redox series, revealing mostly ligand-centered
      electron transfer: [(acac)(2)Ru(III)(L(0))](+) ? [(acac)(2)Ru(III)(L(*-))] ?
      [(acac)(2)Ru(III)(L(2-))](-)/[(acac)(2)Ru(II)(L(*-))](-), and
      [(bpy)(2)Ru(III)(L(*-))](2+)/[(bpy)(2)Ru(II)(L(0))](2+) ? [(bpy)(2)Ru(II)(L(*
      ))](+) ? [(bpy)(2)Ru(II)(L(2-))](0). The differences between the O and S
      containing compounds are rather small in comparison to the effects of the
      ancillary ligands, acac(-) versus bpy.

PMID- 22594926
TI  - Effects of high glucose on AVP-induced hyperplasia, hypertrophy, and type IV
      collagen synthesis in cultured rat mesangial cells.
AB  - INTRODUCTION: Hyperglycemia is a principal characteristic of diabetes and
      influences many cellular functions. Diabetic nephropathy is characterized by
      glomerular mesangial expansion which could result from increased mesangial cell
      extracellular matrix synthesis induced by hyperglycemia. METHODS: To investigate
      whether the physiological functions of mesangial cells are altered in a diabetic
      environment, we evaluated the effect of high extracellular glucose concentration
      on thymidine/leucine incorporation, hyperplasia/hypertrophy, and type IV collagen
      synthesis, induced by vasopressin (AVP), in cultured rat mesangial cells.
      RESULTS: The exposure of mesangial cells to a high glucose concentration (30 mM)
      significantly reduced AVP-induced thymidine incorporation and hyperplasia
      compared with normal glucose (10 mM). By contrast, treatment of mesangial cells
      with AVP in the presence of high extracellular glucose significantly increased
      leucine incorporation, hypertrophy, and type IV collagen synthesis compared with
      those at normal glucose levels. The administration of staurosporine, a protein
      kinase C inhibitor, reversed these effects of high-glucose conditions.
      Furthermore, the nonpeptide AVP V(1A) receptor-selective antagonists potently
      inhibited these AVP-induced physiological responses in mesangial cells cultured
      in high-glucose conditions. CONCLUSIONS: These results demonstrate that high
      glucose suppresses mesangial cell proliferation but enhances hypertrophy and type
      IV collagen synthesis induced by AVP. This increased mesangial cell hypertrophy
      and extracellular matrix synthesis may play a crucial role in the glomerular
      mesangial expansion common to diabetic nephropathy.

PMID- 22594927
TI  - Mon2  is a negative regulator of the monomeric G protein, Arl1.
AB  - Using site-directed mutants of ARL1 predicted to alter nucleotide binding, we
      examined phenotypes associated with the loss of ARL1 , including effects on
      membrane traffic and K (+)  homeostasis. The GTP-restricted allele, ARL[Q72L] ,
      complemented the membrane traffic phenotype (CPY secretion), but not the K (+) 
      homeostasis phenotypes (sensitivity to hygromycin B, steady-state levels of K (+)
      , and accumulation of (86)  Rb (+)  ), while the XTP-restricted mutant,
      ARL1[D130N] , complemented the ion phenotypes, but not the membrane traffic
      phenotype. A GDP-restricted allele, ARL1[T32N] , did not effectively complement
      either phenotype. These results are consistent with a model in which Arl1 has
      three different conformations in vivo. We also explored the relationship between
      ARL1 and MON2 using the synthetic lethal phenotype exhibited by these two genes
      and demonstrated that MON2 is a negative regulator of the GTP-restricted allele
      of ARL1 , ARL1[Q72L] . Finally, we constructed several new alleles predicted to
      alter binding of Arl1 to the sole GRIP domain containing protein in yeast, Imh1,
      and found that ARL1[F52G] and ARL1[Y82G] were unable to complement the loss of
      ARL1 with respect to either the membrane traffic or K (+)  homeostasis
      phenotypes. Our study expands understanding of the roles of Arl1 in vivo.

PMID- 22594928
TI  - Efficacy and safety of bimatoprost 0.03% versus minoxidil 3% in enhancement of
      eyebrows: a randomized, double-blind, split-face comparative study.

PMID- 22594930
TI  - Perspectives on allergen-specific immunotherapy in childhood: an EAACI position
      statement.
AB  - This article is the result of consensus reached by a working group of clinical
      experts in paediatric allergology as well as representatives from an ethical
      committee and the European Medicine Agency (EMA). The manuscript covers clinical,
      scientific, regulatory and ethical perspectives on allergen-specific
      immunotherapy in childhood. Unmet needs are identified. To fill the gaps and to
      bridge the different points of view, recommendations are made to researchers, to
      scientific and patient organizations and to regulators and ethical committees.
      Working together for the benefit of the community is essential. The European
      Academy of Allergy and Clinical Immunology (EAACI) serves as the platform of such
      cooperation.

PMID- 22594931
TI  - A simple method to improve safety of epinephrine auto-injectors.

PMID- 22594932
TI  - SIT: efficacy depends on product, not on route of application.

PMID- 22594934
TI  - Evaluation of an exposure assessment used in epidemiological studies of diesel
      exhaust and lung cancer in underground mines.
AB  - NIOSH/NCI (National Institute of Occupational Safety and Health and National
      Cancer Institute) developed exposure estimates for respirable elemental carbon
      (REC) as a surrogate for exposure to diesel exhaust (DE) for different jobs in
      eight underground mines by year beginning in the 1940s-1960s when diesel
      equipment was first introduced into these mines. These estimates played a key
      role in subsequent epidemiological analyses of the potential relationship between
      exposure to DE and lung cancer conducted in these mines. We report here on a
      reanalysis of some of the data from this exposure assessment. Because samples of
      REC were limited primarily to 1998-2001, NIOSH/NCI used carbon monoxide (CO) as a
      surrogate for REC. In addition, because CO samples were limited, particularly in
      the earlier years, they used the ratio of diesel horsepower (HP) to the mine air
      exhaust rate as a surrogate for CO. There are considerable uncertainties
      connected with each of these surrogate-based steps. The estimates of HP appear to
      involve considerable uncertainty, although we had no data upon which to evaluate
      the magnitude of this uncertainty. A sizable percentage (45%) of the CO samples
      used in the HP to CO model was below the detection limit which required NIOSH/NCI
      to assign CO values to these samples. In their preferred REC estimates, NIOSH/NCI
      assumed a linear relation between C0 and REC, although they provided no credible
      support for that assumption. Their assumption of a stable relationship between HP
      and CO also is questionable, and our reanalysis found a statistically significant
      relationship in only one-half of the mines. We re-estimated yearly REC exposures
      mainly using NIOSH/NCI methods but with some important differences: (i) rather
      than simply assuming a linear relationship, we used data from the mines to
      estimate the CO-REC relationship; (ii) we used a different method for assigning
      values to nondetect CO measurements; and (iii) we took account of statistical
      uncertainty to estimate bounds for REC exposures. This exercise yielded
      significantly different exposure estimates than estimated by NIOSH/NCI. However,
      this analysis did not incorporate the full range of uncertainty in REC exposures
      because of additional uncertainties in the assumptions underlying the modeling
      and in the underlying data (e.g. HP and mine exhaust rates). Estimating
      historical exposures in a cohort is generally a very difficult undertaking.
      However, this should not prevent one from recognizing the uncertainty in the
      resulting estimates in any use made of them.

PMID- 22594935
TI  - A peptide talk between JC virus and the human host: from silent infection to
      autoimmunity.
AB  - Analysis of JC virus (JCV) polyprotein for peptide sharing with the human
      proteome reveals that the virus has hundreds of pentapeptide sequences in common
      with the human proteins. The datum is interesting in light of the fundamental
      role exerted by short amino acid sequences in protein-protein interactions and,
      consequently, in biochemical reactions and immune recognition. Searching for new
      approaches to understand the JCV infection scenarios, from the immunoevasion
      phenomenon underlying the viral asymptomatic stay in the human host to the
      (re)activation phase and associated pathogenic sequelae, the present study
      describes the diffuse pentapeptide communication network between JCV and the
      human host.

PMID- 22594936
TI  - Directional cyclooligomers via alkyne metathesis.
AB  - Macrocyclic oligomers possessing direction-defining ester linkages were
      synthesized via metathesis of the nondirectional alkyne functional group. Alkyne
      metathesis is expected to scramble the relative orientation of adjacent ester
      groups, potentially leading to a complex mixture of macrocyclic products. We
      wondered whether a narrow product distribution would be achievable with a proper
      choice of the building block structure. Here we show that the shape of the
      building block determines whether the macrocyclic products are directionally
      uniform or scrambled. Specifically, two isomeric arylene-ethynylene polyesters
      afforded significantly different product distributions upon being subjected to
      depolymerization-macrocyclization. These results underscore the importance of
      learning how the shape and geometry of the building blocks affect the
      macrocyclization energy landscape.

PMID- 22594937
TI  - Analysis of the structural and immunological stability of 2S albumin, nonspecific
      lipid transfer protein, and profilin allergens from mustard seeds.
AB  - This work investigates the resistance to proteolysis and heating of the yellow
      mustard (Sinapis alba L.) allergens Sin a 1 (2S albumin), Sin a 3 (nonspecific
      lipid transfer protein, LTP), and Sin a 4 (profilin) to explain their potential
      capability to induce primary sensitization at the gastrointestinal level. Sin a 1
      and Sin a 3 resisted gastric digestion showing no reduction of the IgE
      reactivity. Intestinal digestion of Sin a 1 and Sin a 3 produced a limited
      proteolysis but retained significant IgE-binding reactivity. Sin a 1 was stable
      after heating, and although Sin a 3 was modified, most of its structure was
      recovered after cooling back. These two allergens would be therefore able to
      sensitize by ingestion. Sin a 4 was completely digested by gastric treatment and
      its conformational structure markedly modified at 85  degrees C. Thus, this
      allergen can be described as a nonsensitizing mustard allergen. 

PMID- 22594938
TI  - Laser-induced liquid bead ion desorption mass spectrometry: an approach to
      precisely monitor the oligomerization of the beta-amyloid peptide.
AB  - In the present work, the recently developed laser-induced liquid bead ion
      desorption mass spectrometry (LILBID MS) is applied as a novel technique to study
      Abeta oligomerization, thought to be crucial in Alzheimer's disease (AD). The
      characterization of the earliest nucleation events of this peptide necessitates
      the application of several techniques to bridge the gap between small oligomers
      and large fibrils. We precisely monitored in time the transformation of monomeric
      Abeta (1-42) into oligomeric Abeta(n) (n < 20) and its dependence on
      concentration and agitation. The distribution shows signs of the hexamer being
      crucial in the assembly process. The intensity of the monomer decreases in time
      with a time constant of about 9 h. After a lag time of around 10 h, a phase
      transition occurred in which the total ion current of the oligomers goes to
      nearly zero. In this late stage of aggregation, protofibrils are formed and mass
      spectrometry is no longer sensitive. Here fluorescence correlation spectroscopy
      (FCS) and transmission electron microscopy (TEM) are complementary tools for
      detection and size characterization of these large species. We also utilized the
      oligomers of Abeta (1-42) as a model of the corresponding in vivo process to
      screen the efficacy and specificity of small molecule inhibitors of
      oligomerization. The LILBID results are in excellent agreement with condensed
      phase behavior determined in other studies. Our data identified LILBID MS as a
      powerful technique that will advance the understanding of peptide oligomerization
      in neurodegenerative diseases and represents a powerful tool for the
      identification of small oligomerization inhibitors.

PMID- 22594939
TI  - Unintentional drowning in urban South Africa: a retrospective investigation, 2001
      2005.
AB  - Drowning is a major public health concern in low- and middle-income countries. In
      South Africa there is sound information and an emerging knowledge base for
      drowning prevention. However, there remains a scarcity of analyses of drowning in
      the country. The purpose of this analysis was to quantify the magnitude and
      describe occurrence of unintentional drowning deaths in five major South African
      cities, recorded between 2001 and 2005 by the National Injury Mortality
      Surveillance System. Drowning in South African cities occurred at rates of
      between 1.4 and 2.7/100,000 population. The majority of drowning occurred among
      males, while the highest rates were observed among 0-4 year olds. Most drowning
      deaths occurred during recreational periods, over weekends and in the afternoon.
      Of adult drowning victims, 41.5% were alcohol-positive at the time of death. This
      study is based on one of only two known systematic sources of drowning mortality
      in Africa. It provides an indication of drowning rates in South African cities
      with young children and males at considerably more risk. The most likely
      locations for drowning varied from city to city. Among adult victims, especially
      men, alcohol is an important risk factor. 

PMID- 22594940
TI  - Selection in a fluctuating environment and the evolution of sexual dimorphism in
      the seed beetle Callosobruchus maculatus.
AB  - Temperature changes in the environment, which realistically include environmental
      fluctuations, can create both plastic and evolutionary responses of traits. Sexes
      might differ in either or both of these responses for homologous traits, which in
      turn has consequences for sexual dimorphism and its evolution. Here, we
      investigate both immediate changes in and the evolution of sexual dimorphism in
      response to a changing environment (with and without fluctuations) using the seed
      beetle Callosobruchus maculatus. We investigate sex differences in plasticity and
      also the genetic architecture of body mass and developmental time dimorphism to
      test two existing hypotheses on sex differences in plasticity (adaptive
      canalization hypothesis and condition dependence hypothesis). We found a
      decreased sexual size dimorphism in higher temperature and that females responded
      more plastically than males, supporting the condition dependence hypothesis.
      However, selection in a fluctuating environment altered sex-specific patterns of
      genetic and environmental variation, indicating support for the adaptive
      canalization hypothesis. Genetic correlations between sexes (r(MF) ) were
      affected by fluctuating selection, suggesting facilitated independent evolution
      of the sexes. Thus, the selective past of a population is highly important for
      the understanding of the evolutionary dynamics of sexual dimorphism.

PMID- 22594941
TI  - A new approach for cytokinin isolation from Arabidopsis tissues using
      miniaturized purification: pipette tip solid-phase extraction.
AB  - BACKGROUND: We have developed a new analytical approach for isolation and
      quantification of cytokinins (CK) in minute amounts of fresh plant material,
      which combines a simple one-step purification with ultra-high performance liquid
      chromatography-fast scanning tandem mass spectrometry. RESULTS: Plant tissue
      samples (1-5 mg FW) were purified by stop-and-go-microextraction (StageTip
      purification), which previously has only been applied for clean-up and pre
      concentration of peptides. We found that a combination of two reverse phases and
      one cation-exchange phase, was the best tool, giving a total extraction recovery
      higher than 80%. The process was completed by a single chromatographic analysis
      of a wide range of naturally occurring cytokinins (bases, ribosides, O- and N
      glucosides, and nucleotides) in 24.5 minutes using an analytical column packed
      with sub-2-microne particles. In multiple reaction monitoring mode, the detection
      limits ranged from 0.05 to 5 fmol and the linear ranges for most cytokinins were
      at least five orders of magnitude. The StageTip purification was validated and
      optimized using samples of Arabidopsis thaliana seedlings, roots and shoots where
      eighteen cytokinins were successfully determined. CONCLUSIONS: The combination of
      microextraction with one-step high-throughput purification provides fast,
      effective and cheap sample preparation prior to qualitative and quantitative
      measurements. Our procedure can be used after modification also for other
      phytohormones, depending on selectivity, affinity and capacity of the selected
      sorbents.

PMID- 22594942
TI  - Unprecedented "In Water" imidazole carbonylation: paradigm shift for preparation
      of urea and carbamate.
AB  - The first "In Water" imidazolecarbonylation of amine is described. A one pot
      reaction of carbonylimidazolide in water with a nucleophile provides an efficient
      and general method for the preparation of urea, carbamates and thiocarbamates.
      Use of an anhydrous solvent and an inert atmosphere could be avoided. Product
      precipitate out from the reaction mixture and can be obtained in high purity by
      filtration, resulting in a simple and scalable method.

PMID- 22594944
TI  - Estimates of medical comorbidities in erectile dysfunction in Taiwan--patient
      based or population-based?

PMID- 22594943
TI  - Striatal dopamine modulates song spectral but not temporal features through D1
      receptors.
AB  - The activity of midbrain dopaminergic neurons and their projection to the basal
      ganglia (BG) are thought to play a critical role in the acquisition of motor
      skills through reinforcement learning, as well as in the expression of learned
      motor behaviors. The precise role of BG dopamine (DA) in mediating and modulating
      motor performance and learning, however, remains unclear. In songbirds, a
      specialized portion of the BG is responsible for song learning and plasticity.
      Previously we found that DA acts on D1 receptors in Area X to modulate the BG
      output signal and thereby trigger changes in song variability. Here, we
      investigate the effect of D1 receptor blockade in the BG on song behavior in the
      zebra finch. We report that this manipulation abolishes social context-dependent
      changes in variability not only in harmonic stacks, but also in other types of
      syllables. However, song timing seems not to be modulated by this BG DA signal.
      Indeed, injections of a D1 antagonist in the BG altered neither song duration nor
      the change of song duration with social context. Finally, D1 receptor activation
      in the BG was not necessary for the modulation of other features of song, such as
      the number of introductory notes or motif repetitions. Together, our results
      suggest that activation of D1 receptors in the BG is necessary for the modulation
      of fine acoustic features of song with social context, while it is not involved
      in the regulation of song timing and structure at a larger time scale.

PMID- 22594946
TI  - Neuropeptide Y loses its orexigenic effect in rats with lesions of the
      hypothalamic paraventricular nucleus.
AB  - BACKGROUND: Both neuropeptide Y (NPY) and ghrelin can enhance the feeding
      behavior. The purpose of this study was to determine whether NPY and ghrelin are
      involved in hyperphagia and obesity induced by lesions of the hypothalamic
      paraventricular nucleus (PVN). METHODS: Sham-operated control rats and rats
      subjected to bilateral electrolytic lesions of the PVN were administered NPY (5
      MUg/rat) by intracerebroventricular infusion or ghrelin (20 MUg/kg) by
      intraperitoneal (i.p.) injection. Control rats were administered the appropriate
      vehicle by the same route as the drug. We measured the cumulative food intake
      (FI) for 2 h after infusion of NPY and for 4 h after ghrelin injection. RESULTS:
      NPY significantly increased the cumulative FI in sham-operated rats. In PVN
      lesioned rats, however, the cumulative FI at each time point (15 min, 30 min, 1
      h, and 2 h) after NPY infusion was not significantly different from vehicle
      infusion, showing that NPY lost its orexigenic effect in PVN-lesioned rats.
      Following ghrelin injection, the cumulative FI was greater in PVN-lesioned rats
      than sham-operated rats, indicating that PVN lesions enhanced the orexigenic
      effects of ghrelin. CONCLUSION: These results suggest that the hyperphagia and
      obesity induced by PVN lesions may be related to an increased orexigenic action
      of ghrelin, but not NPY.

PMID- 22594945
TI  - Protective effects of peroxisome proliferator-activated receptor agonists on
      human podocytes: proposed mechanisms of action.
AB  - BACKGROUND AND PURPOSE: Peroxisome proliferator-activated receptor (PPAR)
      agonists exert anti-albuminuric effects. However, the nephroprotective effects of
      these drugs remain to be fully understood. We have investigated whether
      gemfibrozil, GW0742 and pioglitazone protect human podocytes against nutrient
      deprivation (ND)-induced cell death and the role of mitochondrial biogenesis as a
      cytoprotective process. EXPERIMENTAL APPROACH: Immortalized human podocytes were
      pre-treated with the PPAR agonists and exposed to ND (5 h) under normoxia,
      hypoxia or in the presence of pyruvate. Cell death was measured at the end of the
      ND and of the recovery phase (24 h). Mitochondrial mass, cytochrome c oxidase
      (COX) subunits 1 and 4 were measured as markers of mitochondrial cell content,
      while membrane potential as an index of mitochondrial function. PGC-1alpha, NRF1
      and Tfam expression was studied, as crucial regulators of mitochondrial
      biogenesis. KEY RESULTS: Cell pre-treatment with gemfibrozil, GW0742, or
      pioglitazone significantly decreased the ND-induced cell loss, necrosis and
      apoptosis. These effects were attenuated by hypoxia and potentiated by pyruvate.
      Pre-treatment with these drugs significantly increased mitochondrial cell
      content, while it did not affect mitochondrial function. In all these experiments
      pioglitazone exerted significantly larger effects than gemfibrozil or GW0742.
      CONCLUSIONS AND IMPLICATIONS: Gemfibrozil, GW0742 and pioglitazone may exert
      direct protective effects on human podocytes. Mitochondrial biogenesis is a cell
      response to the PPAR agonists related to their cytoprotective activity. These
      results provide a mechanistic support to the clinical evidence indicating PPAR
      agonists as disease-modifying agents for glomerular diseases.

PMID- 22594947
TI  - Antipsychotic treatment of acute paranoid schizophrenia patients with olanzapine
      results in altered glycosylation of serum glycoproteins.
AB  - Atypical antipsychotic drugs, such as olanzapine, have been shown to alleviate
      the positive, negative and, to a lesser degree, the cognitive symptoms of
      schizophrenia in many patients. However, the detailed mechanisms of action of
      these drugs have yet to be elucidated. We have carried out the first
      investigation aimed at evaluating the effects of olanzapine treatment on the
      glycosylation of serum proteins in schizophrenia patients. Olanzapine treatment
      resulted in increased levels of a disialylated biantennary glycan and reduced
      levels of a number of disialylated bi- and triantennary glycans on whole serum
      glycoproteins. These changes were not observed on a low-abundance serum protein
      fraction. alpha1 acid glycoprotein was identified as a carrier of some of the
      detected altered oligosaccharides. In addition, glycan analysis of haptoglobin,
      transferrin, and alpha1 antitrypsin reported similar findings, although these
      changes did not reach significance. Exoglycosidase digestion analysis showed that
      olanzapine treatment increased galactosylation and sialylation of whole serum
      proteins, suggesting increased activity of specific galactosyltransferases and
      increased availability of galactose residues for sialylation. Taken together,
      these findings indicate that olanzapine treatment results in altered
      glycosylation of serum proteins.

PMID- 22594948
TI  - rCUR: an R package for CUR matrix decomposition.
AB  - BACKGROUND: Many methods for dimensionality reduction of large data sets such as
      those generated in microarray studies boil down to the Singular Value
      Decomposition (SVD). Although singular vectors associated with the largest
      singular values have strong optimality properties and can often be quite useful
      as a tool to summarize the data, they are linear combinations of up to all of the
      data points, and thus it is typically quite hard to interpret those vectors in
      terms of the application domain from which the data are drawn. Recently, an
      alternative dimensionality reduction paradigm, CUR matrix decompositions, has
      been proposed to address this problem and has been applied to genetic and
      internet data. CUR decompositions are low-rank matrix decompositions that are
      explicitly expressed in terms of a small number of actual columns and/or actual
      rows of the data matrix. Since they are constructed from actual data elements,
      CUR decompositions are interpretable by practitioners of the field from which the
      data are drawn. RESULTS: We present an implementation to perform CUR matrix
      decompositions, in the form of a freely available, open source R-package called
      rCUR. This package will help users to perform CUR-based analysis on large-scale
      data, such as those obtained from different high-throughput technologies, in an
      interactive and exploratory manner. We show two examples that illustrate how CUR
      based techniques make it possible to reduce significantly the number of probes,
      while at the same time maintaining major trends in data and keeping the same
      classification accuracy. CONCLUSIONS: The package rCUR provides functions for the
      users to perform CUR-based matrix decompositions in the R environment. In gene
      expression studies, it gives an additional way of analysis of differential
      expression and discriminant gene selection based on the use of statistical
      leverage scores. These scores, which have been used historically in diagnostic
      regression analysis to identify outliers, can be used by rCUR to identify the
      most informative data points with respect to which to express the remaining data
      points.

PMID- 22594949
TI  - Are the stages of change relevant for the development and implementation of a web
      based tailored alcohol intervention? A cross-sectional study.
AB  - BACKGROUND: Computer-tailored programs are a promising tool to stimulate health
      behavior change, such as reducing alcohol intake. Yet more research is needed to
      assess whether groups differing in their motivational level to change may need
      different types of feedback. Furthermore, it is unknown whether motivational
      level may also determine reactions to computer-tailored interventions. Our aim is
      to identify the potential relevance of the application of the stages of change
      concept in the development and implementation of alcohol interventions. METHODS:
      A web-based instrument was used to disseminate a questionnaire and to provide
      tailored feedback messages among adults in the Netherlands (N = 170; 96 females).
      Motivational level was assessed by the stage of change construct. The survey
      furthermore assessed alcohol consumption, attitude, social influence, self
      efficacy, and program evaluation (i.e., survey items, tailored advice, layout and
      functionality of the program). The Least Significant Difference method was used
      to compare people in different stages of change with regard to psychosocial
      determinants of drinking behavior and program evaluation. RESULTS: Of the
      respondents, 34.1% (n = 58) reported no intention to change to healthier drinking
      habits in the foreseeable future (precontemplation), 22.9% (n = 39) intended to
      improve their drinking behavior in the near future (contemplation/preparation)
      and 42.9% (n = 73) reported to currently adhere to the Dutch alcohol consumption
      guidelines (action/maintenance). When comparing the three groups, people in the
      action or maintenance stage reported the lowest number of pros of drinking
      alcohol, having most healthy drinking role models and the highest levels of self
      efficacy regarding healthy drinking in difficult situations, whereas
      precontemplators reported to receive the least social support regarding healthy
      drinking. In general, the intervention was positively evaluated, but it seemed to
      be most appreciated by contemplators and preparers. CONCLUSIONS: Stage-matched
      interventions may be useful to encourage people to reduce their alcohol intake.
      Different factors seem to be important for people in different motivational
      stages. Longitudinal studies are needed to determine whether these factors also
      predict stage transition. The intervention could be optimized by tailoring the
      feedback messages more precisely to the needs of people in different motivational
      stages, for example by applying the different processes of change.

PMID- 22594950
TI  - Cyclopentadienyl-silsesquioxane titanium complexes: highly active catalysts for
      epoxidation of alkenes with aqueous hydrogen peroxide.
AB  - Titanium complexes bearing an unprecedented tridentate cyclopentadienyl
      silsesquioxanate ligand provide a new class of efficient and selective catalysts
      for epoxidation of olefins with aqueous hydrogen peroxide under homogeneous
      conditions.

PMID- 22594951
TI  - Particle formation during oxidation catalysis with Cp* iridium complexes.
AB  - Real-time monitoring of light scattering and UV-vis profiles of four different
      Cp*Ir(III) precursors under various conditions give insight into nanoparticle
      formation during oxidation catalysis with NaIO(4) as primary oxidant. Complexes
      bearing chelate ligands such as 2,2'-bipyridine, 2-phenylpyridine, or 2-(2'
      pyridyl)-2-propanolate were found to be highly resistant toward particle
      formation, and oxidation catalysis with these compounds is thus believed to be
      molecular in nature under our conditions. Even with the less stable hydroxo/aqua
      complex [Cp*(2)Ir(2)(MU-OH)(3)]OH, nanoparticle formation strongly depended on
      the exact conditions and elapsed time. Test experiments on the isolated particles
      and comparison of UV-vis data with light scattering profiles revealed that the
      formation of a deep purple-blue color (~580 nm) is not indicative of particle
      formation during oxidation catalysis with molecular iridium precursors as
      suggested previously.

PMID- 22594952
TI  - The Muslim football player and Ramadan: current challenges.
AB  - Islam is a monotheistic Abrahamic faith characterised by devotional orthopraxy.
      The actions expected of followers of Islam are closely prescribed in the Qur'an.
      Muslims understand Ramadan as a mandatory requirement, excused only in the event
      of illness, infirmity or extremes of age. Due to the increasing popularity of
      football among Muslims, more and more Muslim football players of all levels make
      the decision to follow the Ramadan fast while they need to practise and compete.
      Sports medicine clinicians and scientists have the responsibility to provide them
      with the knowledge and evidence on how exactly Ramadan fasting impacts on their
      performance and how to optimise their eating, drinking and sleeping in order to
      minimise negative effects of their religious practice, should any have been
      demonstrated. The first International Federation of Football Associations (FIFA)
      Medical Assessment and Research Centre (F-MARC) study concluded that biochemical,
      nutritional, subjective well-being and performance variables were not adversely
      affected in young male national level players who followed Ramadan fasting in a
      controlled environment. Match performance was however not measured and the study
      did not include elite level players, leading to the Ramadan consensus meeting in
      order to answer the remaining questions. The conclusions and recommendations
      published in this supplement suggest that the best coping strategies will remain
      individual - as is the choice to fast.

PMID- 22594953
TI  - Hypothermic machine preservation reduces molecular markers of
      ischemia/reperfusion injury in human liver transplantation.
AB  - Hypothermic machine perfusion (HMP) is in its infancy in clinical liver
      transplantation. Potential benefits include diminished preservation injury (PI)
      and improved graft function. Molecular data to date has been limited to
      extrapolation of animal studies. We analyzed liver tissue and serum collected
      during our Phase 1 trial of liver HMP. Grafts preserved with HMP were compared to
      static cold stored (SCS) transplant controls. Reverse transcription polymerase
      chain reaction (RT-PCR), immunohistochemistry and transmission electron
      microscopy (TEM) were performed on liver biopsies. Expression of inflammatory
      cytokines, adhesion molecules and chemokines, oxidation markers, apoptosis and
      acute phase proteins and the levels of CD68 positive macrophages in tissue
      sections were evaluated. RT-PCR of reperfusion biopsy samples in the SCS group
      showed high expression of inflammatory cytokines, adhesion molecules and
      chemokines, oxidative markers and acute phase proteins. This upregulation was
      significantly attenuated in livers that were preserved by HMP. Immunofluorescence
      showed larger numbers of CD68 positive macrophages in the SCS group when compared
      to the HMP group. TEM samples also revealed ultrastructural damage in the SCS
      group that was not seen in the HMP group. HMP significantly reduced
      proinflammatory cytokine expression, relieving the downstream activation of
      adhesion molecules and migration of leukocytes, including neutrophils and
      macrophages when compared to SCS controls.

PMID- 22594955
TI  - Prevalence, risk factors and clinical signs predictive for equine pituitary pars
      intermedia dysfunction in aged horses.
AB  - REASONS FOR PERFORMING STUDY: Equine pituitary pars intermedia dysfunction (PPID)
      is an ageing-related neurodegenerative disorder. The prevalence and risk factors
      for PPID using seasonally adjusted basal adrenocorticotropic hormone (ACTH)
      concentrations in aged horses have not been previously reported. OBJECTIVES: To
      determine the prevalence, risk factors and clinical signs predictive for PPID in
      a population of horses aged >= 15 years in Queensland, Australia. METHODS: Owner
      reported data was obtained using a postal questionnaire distributed to an
      equestrian group. A subgroup of surveyed owners were visited and a veterinary
      physical examination performed on all horses aged >= 15 years. Blood samples were
      analysed for basal plasma alpha melanocyte-stimulating hormone (alpha-MSH) and
      ACTH concentrations, routine haematology and selected biochemistry. Aged horses
      with elevations above seasonally adjusted cut-off values for basal plasma ACTH
      were considered positive for PPID. Positive horses were compared with their aged
      counterparts to determine risk factors and clinical signs associated with PPID.
      RESULTS: Pituitary pars intermedia dysfunction was prevalent in aged horses
      (21.2%) despite owners infrequently reporting it as a known or diagnosed disease
      or disorder. Numerous clinical or historical signs were associated with an
      increased risk of PPID in the univariable model, but only age (odds ratio (OR)
      1.18; 95% confidence interval (CI) 1.11-1.25, P<0.001) and owner-reported history
      of hirsutism (OR 7.80; 95% CI 3.67-16.57, P<0.001) remained in the final
      multivariable model. There were no routine haematological or biochemical
      variables supportive of a diagnosis of PPID. CONCLUSIONS AND POTENTIAL RELEVANCE:
      Pituitary pars intermedia dysfunction occurs commonly in aged horses despite
      under-recognition by owners. The increased risk of PPID with age supports that
      this is an ageing associated condition. Aged horses with clinical or historical
      signs consistent with PPID, especially owner-reported hirsutism (delayed shedding
      and/or long hair coat), should be tested and appropriate treatment instituted.

PMID- 22594956
TI  - A fluorescent dipyrrinone oxime for the detection of pesticides and other
      organophosphates.
AB  - An N,N-carbonyl-bridged dipyrrinone oxime has been synthesized and studied as a
      potential sensor for organophosphates. The molecular sensor underwent a drastic
      colorimetric response upon formation of the adduct. The pesticide dimethoate was
      found to produce the biggest spectral response, with a limit of detection equal
      to 4.0 ppm using UV-visible spectroscopy. Minimal fluorescence "turn on" via a
      PET mechanism was seen, and molecular modeling studies were used to explain the
      lower than expected PET response. The X-ray crystal structure of the fluorescent
      dipyrrinone oxime was also obtained.

PMID- 22594957
TI  - Evolution of sexual dichromatism in relation to nesting habits in European
      passerines: a test of Wallace's hypothesis.
AB  - Wallace proposed in 1868 that natural rather than sexual selection could explain
      the striking differences in avian plumage dichromatism. Thus, he predicted that
      nesting habits, through their association with nest predation, could drive
      changes in sexual dichromatism by enabling females in cavity nesters to become as
      conspicuous as males, whereas Darwin (1871, The Descent of Man and Selection in
      Relation to Sex, John Murray, London) argued that sexual selection was the sole
      explanation for dichromatism. Sexual dichromatism is currently used as indicating
      the strength of sexual selection, and therefore testing Wallace's claim with
      modern phylogentically controlled methodologies is of prime interest for
      comparing the roles of natural and sexual selection in affecting the evolution of
      avian coloration. Here, we have related information on nest attendance, sexual
      dichromatism and nesting habits (open and cavity nesting) to male and female
      plumage conspicuousness in European passerines. Nest incubation attendance does
      not explain male or female plumage conspicuousness but nest type does. Moreover,
      although females of monochromatic and cavity nesting species are more conspicuous
      than females of other species, males of monochromatic and open nesting species
      are those with more cryptic plumage. Finally, analyses of character evolution
      suggest that changes in nesting habits influence the probability of changes in
      both dichromatism and plumage conspicuousness of males but do not significantly
      affect those in females. These results strongly suggest a role of nesting habits
      in the evolution of plumage conspicuousness of males, and a role for sexual
      selection also in females, both factors affecting the evolution of sexual
      dichromatism. We discuss our findings in relation to the debate that Darwin and
      Wallace maintained more than one century ago on the importance of natural and
      sexual selection in driving the evolution of plumage conspicuousness and sexual
      dichromatism in birds, and conclude that our results partly support the
      evolutionary scenarios envisaged by both extraordinary scientists.

PMID- 22594958
TI  - Patient satisfaction with topical ocular hypotensives.
AB  - BACKGROUND: The aim of this study is to assess patient satisfaction, convenience
      of use, ease of administration, side effects and treatment burden of topical
      ocular hypotensives. DESIGN: Prospective, observational cohort. PARTICIPANTS: Two
      thousand five hundred and forty-one patients with glaucoma or ocular
      hypertension. METHODS: The Treatment Impact Patient Satisfaction Scale (TIPSS)
      was administered by mail to all patients with glaucoma or ocular hypertension
      registered with Glaucoma New Zealand during a 3-month study period. The
      questionnaire assessed patient demographics; topical ocular hypotensive use
      including number of medications, frequency of administration, ease of use, class
      of medication, and presence/severity of side effects; impact on quality of life;
      and patient satisfaction. Univariate and multivariate analyses were performed to
      identify determinants of patient satisfaction. MAIN OUTCOME MEASURES: Patient
      satisfaction. RESULTS: Almost 80% of respondents were either 'very satisfied' or
      'satisfied' with topical ocular hypotensives. Factors that were predictive of
      patient satisfaction included satisfaction with frequency of eye drop use {odds
      ratio (OR) 2.4 (95% confidence interval [CI] 1.8-3.1); P < 0.001}, subjective
      convenience (OR 2.6 [95% CI 2.0-3.4]; P < 0.001) and ease of administration (OR
      2.5 [95% CI 2.0-3.3]; P < 0.001). Male gender was associated with lower
      satisfaction (OR 0.6 [95% CI 0.5-0.9]; P = 0.01). Factors that were not
      predictive of patient satisfaction included age, duration of eye drop use, class
      of medication and the presence of side effects. CONCLUSIONS: Patients with
      glaucoma and ocular hypotension are satisfied with topical ocular hypotensives.
      Efforts to improve patient satisfaction should focus on convenience and ease of
      administration.

PMID- 22594959
TI  - Birdshot retinochoroidopathy masquerading as intraocular lymphoma.
AB  - We present a case of a patient with bilateral posterior uveitis HLA-A29 positive,
      masquerading intraocular lymphoma. A 43 year-old woman presented with bilateral
      vitritis and chorioretinal lesions compatible with "birdshot lesions". The
      patient was initially diagnosed with birdshot retinochoroidopathy and later on,
      during follow up, the occurrence of neurologic involvement and the lack of
      response to systemic immunosuppression led us to re-evaluate the diagnosis. A
      definite diagnosis of intraocular lymphoma with central nervous system
      involvement was made. This case is presented to highlight the importance of
      careful follow-up of patients with chronic uveitis and re-evaluation of systemic
      symptoms and signs, in particular when ocular findings are highly suggestive for
      masquerade syndrome.

PMID- 22594960
TI  - Multimodality diagnostic imaging in a case of sympathetic ophthalmia.

PMID- 22594961
TI  - Severe phimosis leading to obstructive uropathy in a boy with lichen sclerosus.
AB  - Lichen sclerosus (LS) is a chronic, inflammatory condition which commonly
      involves the anogenital skin. This condition may affect the foreskin, glans,
      frenulum, meatus and urethra in males. It manifests itself with voiding symptoms.
      Obstructive uropathy is an extremely rare clinical presentation in childhood.
      This study reports the case of a 13-year-old boy presenting with obstructive
      uropathy due to LS and reviews the published data on the diagnosis, management
      and follow-up of this condition.

PMID- 22594962
TI  - Improving memory in outpatients with neurological disorders using a group-based
      training program.
AB  - Memory problems are common in patients with a range of neurological conditions,
      but there have been few attempts to provide and evaluate the usefulness of memory
      training for groups of neurological outpatients. We used a waitlist-controlled
      trial design to assess the effectiveness of a newly created, 6-session
      intervention, which involved training in the use of compensatory strategies as
      well as education regarding memory function, neurological damage, sleep and
      lifestyle factors that have an impact on memory. Fifty-six patients with
      neurological conditions (e.g., stroke, epilepsy) and memory complaints completed
      the training and assessments. Outcomes were evaluated in terms of reported
      strategy use as well as objective and subjective measures of anterograde and
      prospective memory. Training resulted in significant improvements on number of
      strategies used, scores on the Rey Auditory Verbal Learning Test (total learning
      and delayed recall) and self-report on the Comprehensive Assessment of
      Prospective Memory. Improvements were stable at 3-month follow-up. Better
      individual outcomes were related to lower baseline memory scores, fewer symptoms
      of depression and greater self-awareness of memory function. Overall the study
      provides encouraging results to indicate that patients with neurological
      conditions such as stroke and epilepsy can show improvements in memory after a
      relatively short group-based intervention.

PMID- 22594964
TI  - Hydration and performance during Ramadan.
AB  - In the absence of any food or fluid intake during the hours of daylight during
      the month of Ramadan, a progressive loss of body water will occur over the course
      of each day, though these losses can be completely replaced each night. Large
      body water deficits will impair both physical and cognitive performance. The
      point at which water loss will begin to affect performance is not well defined,
      but it may be as little as 1-2% of body mass. For resting individuals in a
      temperate environment, the water loss that occurs during a day without food or
      fluid will typically amount to about 1% of body mass by the time of sunset. This
      small loss of body water is unlikely to have a major adverse effect on any aspect
      of physical or cognitive performance. Larger body water losses will occur,
      however, in hot weather or if exercise is undertaken. Performance in events
      lasting about 1 hour or longer may be impaired in the absence of fluid intake
      during the event. In weight-category sports, there may be difficulties due to the
      impossibility of restoring body water content between the weigh-in and
      competition, and athletes will require alternative strategies. Where more than
      one competition or training session takes place in a single day and where
      substantial fluid losses are incurred, recovery will be impaired by the absence
      of fluid intake.

PMID- 22594963
TI  - Non-THC cannabinoids inhibit prostate carcinoma growth in vitro and in vivo: pro
      apoptotic effects and underlying mechanisms.
AB  - BACKGROUND AND PURPOSE: Cannabinoid receptor activation induces prostate
      carcinoma cell (PCC) apoptosis, but cannabinoids other than Delta(9) 
      tetrahydrocannabinol (THC), which lack potency at cannabinoid receptors, have not
      been investigated. Some of these compounds antagonize transient receptor
      potential melastatin type-8 (TRPM8) channels, the expression of which is
      necessary for androgen receptor (AR)-dependent PCC survival. EXPERIMENTAL
      APPROACH: We tested pure cannabinoids and extracts from Cannabis strains enriched
      in particular cannabinoids (BDS), on AR-positive (LNCaP and 22RV1) and -negative
      (DU-145 and PC-3) cells, by evaluating cell viability (MTT test), cell cycle
      arrest and apoptosis induction, by FACS scans, caspase 3/7 assays, DNA
      fragmentation and TUNEL, and size of xenograft tumours induced by LNCaP and DU
      145 cells. KEY RESULTS: Cannabidiol (CBD) significantly inhibited cell viability.
      Other compounds became effective in cells deprived of serum for 24 h. Several BDS
      were more potent than the pure compounds in the presence of serum. CBD-BDS (i.p.)
      potentiated the effects of bicalutamide and docetaxel against LNCaP and DU-145
      xenograft tumours and, given alone, reduced LNCaP xenograft size. CBD (1-10 uM)
      induced apoptosis and induced markers of intrinsic apoptotic pathways (PUMA and
      CHOP expression and intracellular Ca(2+)). In LNCaP cells, the pro-apoptotic
      effect of CBD was only partly due to TRPM8 antagonism and was accompanied by down
      regulation of AR, p53 activation and elevation of reactive oxygen species. LNCaP
      cells differentiated to androgen-insensitive neuroendocrine-like cells were more
      sensitive to CBD-induced apoptosis. CONCLUSIONS AND IMPLICATIONS: These data
      support the clinical testing of CBD against prostate carcinoma.

PMID- 22594965
TI  - Comparison of 4-plex to 8-plex iTRAQ quantitative measurements of proteins in
      human plasma samples.
AB  - Methods for isobaric tagging of peptides, iTRAQ or TMT, are commonly used
      platforms in mass spectrometry based quantitative proteomics. These two methods
      are very often used to quantitate proteins in complex samples, e.g., serum/plasma
      or CSF supporting biomarker discovery studies. The success of these studies
      depends on multiple factors, including the accuracy of ratios of reporter ions
      reflecting quantitative changes of proteins. Because reporter ions are generated
      during peptide fragmentation, the differences of chemical structure of iTRAQ
      balance groups may have an effect on how efficiently these groups are fragmented
      and thus how differences in protein expression will be measured. Because 4-plex
      and 8-plex iTRAQ reagents do have different structures of balanced groups, it has
      been postulated that indeed differences in protein identification and
      quantitation exist between these two reagents. In this study we controlled the
      ratios of tagged samples and compared quantitation of proteins using 4-plex
      versus 8-plex reagents in the context of a highly complex sample of human plasma
      using ABSciex 4800 MALDI-TOF/TOF mass spectrometer and ProteinPilot 4.0 software.
      We observed that 8-plex tagging provides more consistent ratios than 4-plex
      without compromising protein identification, thus allowing investigation of eight
      experimental conditions in one analytical experiment.

PMID- 22594966
TI  - Doxycycline treatment in a neonatal rat model of hypoxia-ischemia reduces
      cerebral tissue and white matter injury: a longitudinal magnetic resonance
      imaging study.
AB  - Doxycycline may potentially be a neuroprotective treatment for neonatal hypoxic
      ischemic brain injury through its anti-inflammatory effects. The aim of this
      study was to examine any long-term neuroprotection by doxycycline treatment on
      cerebral gray and white matter. Hypoxic-ischemic brain injury was induced in 7
      day-old rats. Pups were treated with either doxycycline (HI+doxy) or saline
      (HI+vehicle) by intraperitoneal injection at 1 h after hypoxia-ischemia (HI). At
      6 h after HI, MnCl(2) was injected intraperitoneally for later manganese-enhanced
      magnetic resonance imaging (MRI). MRI was performed with diffusion-weighted
      imaging on day 1 and T(1) -weighted imaging and diffusion tensor imaging at 7, 21
      and 42 days after HI. Animals were killed after MRI on day 42 and histological
      examinations of the brains were performed. There was a tendency towards lower
      lesion volumes on diffusion maps among HI+doxy than HI+vehicle rats at 1 day
      after HI. Volumetric MRI showed increasing differences between groups with time
      after HI, with less cyst formation and less cerebral tissue loss among HI+doxy
      than HI+vehicle pups. HI+doxy pups had less manganese enhancement on day 7 after
      HI, indicating reduced inflammation. HI+doxy pups had higher fractional
      anisotropy on diffusion tensor imaging in major white matter tracts in the
      injured hemisphere than HI+vehicle pups, indicating less injury to white matter
      and better myelination. Histological examinations supported the MRI results.
      Lesion size on early MRI was highly correlated with final injury measures. In
      conclusion, a single dose of doxycycline reduced long-term cerebral tissue loss
      and white matter injury after neonatal HI, with an increasing effect of treatment
      with time after injury.

PMID- 22594967
TI  - Relationship between vitamin D deficiency and nondipper hypertension.
AB  - Nondipper hypertension is associated with increased cardiovascular morbidity and
      mortality. Vitamin D deficiency is associated with cardiovascular diseases such
      as coronary artery disease, heart failure, and hypertension. Vitamin D deficiency
      activates the renin-angiotensin-aldosterone system, which affects the
      cardiovascular system. For this reason, a relationship between vitamin D
      deficiency and nondipper hypertension could be suggested. In this study, we
      compared 25-OH vitamin D levels between dipper and nondipper hypertensive
      patients. The study included 80 hypertensive patients and they were divided into
      two groups: 50 dipper patients (29 male, mean age 51.5 +/- 8 years) and 30
      nondipper patients (17 male, mean age 50.6 +/- 5.4 years). All the patients were
      subjected to transthoracic echocardiography and ambulatory 24-hour blood pressure
      monitoring. In addition to routine tests, 25-OH vitamin D and parathormone (PTH)
      levels were analyzed. All the patients received antihypertensive drug therapy for
      at least 3 months prior to the evaluations. 25-OH vitamin D and PTH levels were
      compared between the two groups. No statistically significant difference was
      found between the two groups in terms of basic characteristics. The average PTH
      level of hypertensive dipper patients was lower than that of nondipper patients
      (65.3 +/- 14.2 vs. 96.9 +/- 30.8 pg/mL, P < .001). The average 25-OH vitamin D
      level of hypertensive dipper patients was higher than that of nondipper patients
      (21.9 +/- 7.4 vs. 12.8 +/- 5.9 ng/mL, P = .001). The left ventricular mass and
      left ventricular mass index were lower in the dipper patients than in the
      nondipper patients (186.5 +/- 62.1 vs. 246.3 +/- 85.3 g, P = .022; and 111.6 +/-
      21.2 vs.147 +/- 25.7 g/m(2), P < .001, respectively). Other conventional
      echocardiographic parameters were similar between the two groups. Daytime
      systolic and diastolic blood pressure measurements were similar between dippers
      and nondippers, but there was a significant difference between the two groups
      with regard to nighttime measurements (nighttime systolic 118.5 +/- 5.8 vs.130.2
      +/- 9.6 mm Hg, P < .001; and nighttime diastolic 69.3 +/- 4.8 vs.78.1 +/- 7.2 mm
      Hg, P < .001, respectively). Our results suggest that vitamin D deficiency has a
      positive correlation with blood pressure and vitamin D deficiency could be
      related to nondipper hypertension. The measurement of vitamin D may be used to
      indicate increased risk of hypertension-related adverse cardiovascular events.

PMID- 22594968
TI  - SIEDY scale 3, a new instrument to detect psychological component in subjects
      with erectile dysfunction.
AB  - INTRODUCTION: We previously developed and validated a structured interview
      (SIEDY) dealing with the organic (Scale 1), relational (Scale 2), and
      psychological (Scale 3) components of erectile dysfunction (ED). AIM: To identify
      a pathological threshold for SIEDY Scale 3 and to analyze Scale 3 score with
      biological and psychological correlates in subjects with sexual dysfunction.
      METHOD: A pathological threshold of SIEDY Scale 3 score in predicting subjects
      with a medical history of psychopathology and using psychiatric drugs was
      identified through receiver operating characteristic (ROC) curve analysis in a
      sample of 484 patients (Sample A). MAIN OUTCOME MEASURE: Sensitivity and
      specificity, along with possible interactions with biological and psychological
      (Middlesex Hospital Questionnaire, MHQ-score) correlates were verified in a
      further sample of 1,275 patients (Sample B). RESULTS: In sample A, 39 (8%) and 60
      (12.4%) subjects reported a positive medical history for psychiatric disturbances
      or for the use of psychotropic medication, respectively. The association with
      both conditions was present in 28 (5.8%) subjects. ROC curve showed that SIEDY
      Scale 3 score predicts psychopathology with an accuracy of 69.5 +/- 5.9%
      (P<0.002), when a threshold of 3 was chosen. When the same threshold was applied
      in Sample B, it identified a higher ranking in MHQ-A (free-floating anxiety), MHQ
      S (somatized anxiety) and MHQ-D (depressive symptoms) subscales, even after
      adjustment for age and Sigma-MHQ (a broader index of general psychopathology). In
      the same sample, we also confirmed that pathological Scale 3 score was related to
      a higher risk of psychopathology at medical history or to the use of psychotropic
      drugs as well as with risky lifestyle behaviors, including smoking and alcohol
      abuse, and elevated BMI. CONCLUSIONS: SIEDY represents an easy tool for the
      identification of patients with a relevant intra-psychic component who should be
      considered for psychological/psychiatric treatment.

PMID- 22594969
TI  - Correlates of the incidence of disability and mortality among older adult
      Brazilians with and without diabetes mellitus and stroke.
AB  - BACKGROUND: The combined effect of diabetes and stroke on disability and
      mortality remains largely unexplored in Brazil and Latin America. Previous
      studies have been based primarily on data from developed countries. This study
      addresses the empirical gap by evaluating the combined impact of diabetes and
      stroke on disability and mortality in Brazil. METHODS: The sample was drawn from
      two waves of the Survey on Health and Well-being of the Elderly, which followed
      2,143 older adults in Sao Paulo, Brazil, from 2000 to 2006. Disability was
      assessed via measures of activities of daily living (ADL) limitations, severe ADL
      limitations, and receiving assistance to perform these activities. Logistic and
      multinomial regression models controlling for sociodemographic and health
      conditions were used to address the influence of diabetes and stroke on
      disability and mortality. RESULTS: By itself, the presence of diabetes did not
      increase the risk of disability or the need for assistance; however, diabetes was
      related to increased risks when assessed in combination with stroke. After
      controlling for demographic, social and health conditions, individuals who had
      experienced stroke but not diabetes were 3.4 times more likely to have ADL
      limitations than those with neither condition (95% CI 2.26-5.04). This elevated
      risk more than doubled for those suffering from a combination of diabetes and
      stroke (OR 7.34, 95% CI 3.73-14.46). Similar effects from the combination of
      diabetes and stroke were observed for severe ADL limitations (OR 19.75, 95% CI
      9.81- 39.76) and receiving ADL assistance (OR 16.57, 95% CI 8.39-32.73). Over
      time, older adults who had experienced a stroke were at higher risk of remaining
      disabled (RRR 4.28, 95% CI 1.53,11.95) and of mortality (RRR 3.42, 95% CI
      1.65,7.09). However, risks were even higher for those who had experienced both
      diabetes and stroke. Diabetes was associated with higher mortality. CONCLUSIONS:
      Findings indicate that a combined history of stroke and diabetes has a great
      impact on disability prevalence and mortality among older adults in Sao Paulo,
      Brazil.

PMID- 22594970
TI  - Combining adult stem cells and polymeric devices for tissue engineering in
      infarcted myocardium.
AB  - An increasing number of studies in cardiac cell therapy have provided encouraging
      results for cardiac repair. Adult stem cells may overcome ethical and
      availability concerns, with the additional advantages, in some cases, to allow
      autologous grafts to be performed. However, the major problems of cell survival,
      cell fate determination and engraftment after transplantation, still remain.
      Tissue-engineering strategies combining scaffolds and cells have been developed
      and have to be adapted for each type of application to enhance stem cell
      function. Scaffold properties required for cardiac cell therapy are here
      discussed. New tissue engineering advances that may be implemented in combination
      with adult stem cells for myocardial infarction therapy are also presented.
      Biomaterials not only provide a 3D support for the cells but may also mimic the
      structural architecture of the heart. Using hydrogels or particulate systems, the
      biophysical and biochemical microenvironments of transplanted cells can also be
      controlled. Advances in biomaterial engineering have permitted the development of
      sophisticated drug-releasing materials with a biomimetic 3D support that allow a
      better control of the microenvironment of transplanted cells.

PMID- 22594971
TI  - ROS-mediated apoptotic cell death in prostate cancer LNCaP cells induced by
      biosurfactant stabilized CdS quantum dots.
AB  - Cadmium sulfide (CdS) quantum dots (QDs) have raised great attention because of
      their superior optical properties and wide utilization in biological and
      biomedical studies. However, little is known about the cell death mechanisms of
      CdS QDs in human cancer cells. This study was designed to investigate the
      possible mechanisms of apoptosis induced by biosurfactant stabilized CdS QDs
      (denoted as "bsCdS QDs") in human prostate cancer LNCaP cells. It was also
      noteworthy that apoptosis correlated with reactive oxygen species (ROS)
      production, mitochondrial damage, oxidative stress and chromatin condensation in
      a dose- and time-dependent manner. Results also showed involvement of caspases,
      Bcl-2 family proteins, heat shock protein 70, and a cell-cycle checkpoint protein
      p53 in apoptosis induction by bsCdS QDs in LNCaP cells. Moreover, pro-apoptotic
      protein Bax was upregulated and the anti-apoptotic proteins, survivin and NF
      kappaB were downregulated in bsCdS QDs exposed cells. Protection of N-acetyl
      cysteine (NAC) against ROS clearly suggested the implication of ROS in hyper
      activation of apoptosis and cell death. It is encouraging to conclude that
      biologically stabilized CdS QDs bear the potential of its applications in
      biomedicine, such as tumor therapy specifically by inducing caspase-dependent
      apoptotic cell death of human prostate cancer LNCaP cells.

PMID- 22594973
TI  - Quantum-dots based simultaneous detection of multiple biomarkers of tumor stromal
      features to predict clinical outcomes in gastric cancer.
AB  - Tumor microenvironment has been increasingly recognized as a complex and dynamic
      cancer society influencing tumor invasion and progression. The prognostic
      significance of this microenvironment is yet to be fully appreciated. A holistic
      approach to obtaining integrated information on key components in tumor
      microenvironment is essential. Here we reported on a quantum dots (QDs)-based
      simultaneous in-situ detection of infiltrating macrophages, tumor microvessels
      density (MVD) and neovessels maturity, in gastric cancer tissues, to obtain
      integrated information on these components, termed as combined tumor stromal
      features. These stromal features had the comparable prognostic value for overall
      survival, and even better prognostic value for disease-free survival, compared
      with traditional tumor cell-based clinico-pathological parameters. Subgroups of
      gastric cancer patients with favorable and unfavorable combined tumor stromal
      features were identified, with significantly different clinical outcomes. This
      study demonstrated the technical advantages of QDs-based simultaneous detection
      of multiple biomarkers in situ, revealed the important role of tumor stroma in
      cancer biology, and opened a new field to predict clinical outcome in gastric
      cancer from the perspectives of tumor microenvironment.

PMID- 22594972
TI  - Synapse-directed delivery of immunomodulators using T-cell-conjugated
      nanoparticles.
AB  - Regulating molecular interactions in the T-cell synapse to prevent autoimmunity
      or, conversely, to boost anti-tumor immunity has long been a goal in
      immunotherapy. However, delivering therapeutically meaningful doses of immune
      modulating compounds into the synapse represents a major challenge. Here, we
      report that covalent coupling of maleimide-functionlized nanoparticles (NPs) to
      free thiol groups on T-cell membrane proteins enables efficient delivery of
      compounds into the T-cell synapse. We demonstrate that surface-linked NPs are
      rapidly polarized toward the nascent immunological synapse (IS) at the T-cell/APC
      contact zone during antigen recognition. To translate these findings into a
      therapeutic application we tested the NP delivery of NSC-87877, a dual inhibitor
      of Shp1 and Shp2, key phosphatases that downregulate T-cell receptor activation
      in the synapse, in the context of adoptive T cell therapy of cancer. Conjugating
      NSC-87877-loaded NPs to the surface of tumor-specific T cells just prior to
      adoptive transfer into mice with advanced prostate cancer promoted a much greater
      T-cell expansion at the tumor site, relative to co-infusing the same drug dose
      systemically, leading to enhanced survival of treated animals. In summary, our
      studies support the application of T-cell-linked synthetic NPs as efficient drug
      delivery vehicles into the IS, as well as the broad applicability of this new
      paradigm for therapeutically modulating signaling events at the T-cell/APC
      interface.

PMID- 22594974
TI  - The influence of genetic factors on the osteoinductive potential of calcium
      phosphate ceramics in mice.
AB  - The efficacy of calcium phosphate (CaP) ceramics in healing large bone defects
      is, in general, not as high as that of autologous bone grafting. Recently, we
      reported that CaP ceramics with osteoinductive properties were as efficient in
      healing an ilium defect of a sheep as autologous bone graft was, which makes this
      subclass of CaP ceramics a powerful alternative for bone regeneration. Although
      osteoinduction by CaP ceramics has been shown in several large animal models it
      is sporadically reported in mice. Because the lack of a robust mouse model has
      delayed understanding of the mechanism, we screened mice from 11 different inbred
      mouse strains for their responsiveness to subcutaneous implantation of
      osteoinductive tricalcium phosphate (TCP). In only two strains (FVB and 129S2)
      the ceramic induced bone formation, and in particularly, in FVB mice, bone was
      found in all the tested mice. We also demonstrated that other CaP ceramics
      induced bone formation at the same magnitude as that observed in other animal
      models. Furthermore, VEGF did not significantly increase TCP induced bone
      formation. The mouse model here described can accelerate research of
      osteoinductive mechanisms triggered by CaP ceramics and potentially the
      development of therapies for bone regeneration.

PMID- 22594975
TI  - High refractive index polysiloxane as injectable, in situ curable accommodating
      intraocular lens.
AB  - Functionalised siloxane macromonomers, with properties designed for application
      as an injectable, in situ curable accommodating intraocular lens (A-IOL), were
      prepared via re-equilibration of a phenyl group-containing polysiloxane of very
      high molecular weight with octamethylcyclotetrasiloxane (D4) and 2,4,6,8-tetra(n
      propyl-3-methacrylate)-2,4,6,8-tetramethyl-cyclotetrasiloxane (D4(AM)) in toluene
      using trifluoromethanesulfonic acid as a catalyst. Hexaethyldisiloxane was used
      as an end group to control the molecular weight of the polymer. The generated
      polymers had a consistency suitable for injection into the empty lens capsule.
      The polymers contained a low ratio of polymerisable groups so that, in the
      presence of a photo-initiator, they could be cured on demand in situ within 5 min
      under irradiation of blue light to form an intraocular lens within the lens
      capsule. All resulting polysiloxane soft gels had a low elastic modulus and thus
      should be able to restore accommodation. The pre-cure viscosity and post-cure
      modulus of the generated polysiloxanes were controlled by the end group and
      D4(AM) concentrations respectively in the re-equilibration reactions. The
      refractive index could be precisely controlled by adjusting the aromatic ratio in
      the polymer to suit such application as an artificial lens. Lens stretching
      experiments with both human and non-human primate cadaver lenses of different
      ages refilled with polysiloxane polymers provided a significant increase in
      amplitude of accommodation (up to 4 D more than that of the respective natural
      lens). Both in vitro cytotoxicity study using L929 cell lines and in vivo
      biocompatibility study in rabbit models demonstrated the non-cytotoxicity and
      ocular biocompatibility of the polymer.

PMID- 22594976
TI  - Controlling the contractile strength of engineered cardiac muscle by hierarchal
      tissue architecture.
AB  - The heart is a muscular organ with a wrapping, laminar structure embedded with
      neural and vascular networks, collagen fibrils, fibroblasts, and cardiac myocytes
      that facilitate contraction. We hypothesized that these non-muscle components may
      have functional benefit, serving as important structural alignment cues in inter-
      and intra-cellular organization of cardiac myocytes. Previous studies have
      demonstrated that alignment of engineered myocardium enhances calcium handling,
      but how this impacts actual force generation remains unclear. Quantitative assays
      are needed to determine the effect of alignment on contractile function and
      muscle physiology. To test this, micropatterned surfaces were used to build 2
      dimensional myocardium from neonatal rat ventricular myocytes with distinct
      architectures: confluent isotropic (serving as the unaligned control), confluent
      anisotropic, and 20 MUm spaced, parallel arrays of multicellular myocardial
      fibers. We combined image analysis of sarcomere orientation with muscular thin
      film contractile force assays in order to calculate the peak sarcomere-generated
      stress as a function of tissue architecture. Here we report that increasing peak
      systolic stress in engineered cardiac tissues corresponds with increasing
      sarcomere alignment. This change is larger than would be anticipated from
      enhanced calcium handling and increased uniaxial alignment alone. These results
      suggest that boundary conditions (heterogeneities) encoded in the extracellular
      space can regulate muscle tissue function, and that structural organization and
      cytoskeletal alignment are critically important for maximizing peak force
      generation.

PMID- 22594978
TI  - Preliminary clinical report on safety and efficacy of photodynamic therapy using
      talaporfin sodium for malignant gliomas.
AB  - OBJECTIVES: To investigate the safety and efficacy of photodynamic therapy (PDT)
      using talaporfin sodium in patients with surgically, completely unresectable
      malignant gliomas with invasion into the eloquent areas of the brain associated
      with language and motor functions. MATERIALS AND METHODS: Subjects consisted of
      consecutive 14 adult patients with malignant gliomas that were shown on
      preoperative diagnostic imaging to have invaded the eloquent areas of the brain.
      Of these, 6 patients had newly diagnosed tumors and 8 patients had recurrent
      tumors. In 15 craniotomy and tumor resection procedures, PDT was used as
      additional intraoperative treatment 24 h after 40 mg/m(2) of talaporfin sodium
      had been injected intravenously. After the tumor bulk had been resected as
      extensively as possible either 1 or 2 sites of probable tumor invasion in the
      bottom of resection cavity were irradiated superficially with a 664-nm diode
      laser for 180 s (27 J/cm(2)) at a power density of 150 mW/cm(2). RESULTS: PDT
      achieved a response rate of 80% at the treated sites in the 6 patients with newly
      diagnosed malignant gliomas. In these patients, the median progression-free
      survival time was 23 months. The median survival time in 3 patients who died was
      26 months, and the remaining 3 patients survived for more than 3 years with a
      good Karnofsky Performance Scale (KPS). In the 8 patients with recurrent tumors
      who received PDT, their response rate was low (25.0%), their gliomas recurred 3
      months after PDT, and their survival time was only 9 months following PDT. No
      adverse events directly attributable to PDT occurred in any patients. Protection
      against light was only required for approximately 3 days after PDT. CONCLUSION:
      We examined the safety and efficacy of PDT using talaporfin sodium as an
      additional intraoperative treatment for malignant glioma. PDT in addition to
      surgical resection achieved better therapeutic results than conventional
      protocols, especially in patients with newly diagnosed malignant gliomas.
      However, the current methodology has some limitations with respect to patients
      with recurrent tumors. Larger-scale studies are required to confirm the clinical
      feasibility of PDT plus surgery.

PMID- 22594977
TI  - Tissue engineering the monosynaptic circuit of the stretch reflex arc with co
      culture of embryonic motoneurons and proprioceptive sensory neurons.
AB  - The sensory circuit of the stretch reflex arc is composed of intrafusal muscle
      fibers and their innervating proprioceptive neurons that convert mechanical
      information regarding muscle length and tension into action potentials that
      synapse onto the homonymous motoneurons in the ventral spinal cord which
      innervate the extrafusal fibers of the same muscle. To date, the in vitro
      synaptic connection between proprioceptive sensory neurons and spinal motoneurons
      has not been demonstrated. A functional in vitro system demonstrating this
      connection would enable the understanding of feedback by the integration of
      sensory input into the spinal reflex arc. Here we report a co-culture of rat
      embryonic motoneurons and proprioceptive sensory neurons from dorsal root ganglia
      (DRG) in a defined serum-free medium on a synthetic silane substrate (DETA).
      Furthermore, we have demonstrated functional synapse formation in the co-culture
      by immunocytochemistry and electrophysiological analysis. This work will be
      valuable for enabling in vitro model systems for the study of spinal motor
      control and related pathologies such as spinal cord injury, muscular dystrophy
      and spasticity by improving our understanding of the integration of the
      mechanosensitive feedback mechanism.

PMID- 22594979
TI  - Combination of Fospeg-IPDT and a natural antioxidant compound prevents
      photosensitivity in a murine prostate cancer tumour model.
AB  - BACKGROUND: The aim of the present research was to investigate the potential use
      of a natural compound rich in antioxidant agents, derived from Pinus halepensis
      (P. halepensis), to prevent PDT induced photosensitivity. The present research
      progressed in two levels. The first one evolved the optimization of Fospeg
      interstitial photodynamic therapy (IPDT) in a prostate cancer animal model. In
      the second one, P. halepensis bark extract, was evaluated for its potential use
      to prevent photosensitivity. METHODS: Two sets of experiments were performed,
      IPDT only and IPDT in the presence of antioxidant. For both of them, Fospeg was
      administrated intravenously to SCID mice bearing prostate cancer, followed by
      IPDT after 6 h. For the IPDT+antioxidant experiments, P. halepensis was injected
      intratumourously 1 h prior the tumour illumination. Treatment outcome was
      monitored twice a week by an imaging system and by measuring tumour dimensions
      using a caliper. Photosensitivity was assessed by monitoring erythema of the tail
      using the imaging system. RESULTS: IPDT with Fospeg and 15 J total light energy
      is a therapeutic scheme that can eliminate tumours in the murine model of
      prostate cancer. Two months after complete tumour remission no tumour recurrence
      was observed. Also, the cosmetic outcome of the research was excellent. The major
      drawback of this treatment scheme was that 90% of the animals developed
      photosensitivity. The addition of P. halepensis bark extract resulted in
      prevention of the photosensitivity, leaving PDT outcome unaffected. CONCLUSIONS:
      The combined use of PDT and the used antioxidant agent could broaden the
      implementation of photodynamic therapy, by eliminating photosensitivity.

PMID- 22594980
TI  - Vascular targeted photodynamic therapy for bleeding gastrointestinal mucosal
      vascular lesions: a preliminary study.
AB  - BACKGROUND: Vascular-targeted photodynamic therapy (V-PDT) has shown good
      selectivity and efficacy in the treatment of certain types of vascular disease,
      including port wine stains, age-related macular degeneration, and esophageal
      varices. This study was conducted to test the efficacy and safety of V-PDT in the
      treatment of gastrointestinal (GI) bleeding caused by the abnormal dilatation of
      capillaries. METHODS: Patients with bleeding GI mucosal vascular lesions treated
      with V-PDT were included in this retrospective study. The efficiency of V-PDT was
      analyzed by comparing the documented endoscopy results, hemoglobin levels, and
      transfusion requirements before and at 6 months after the last V-PDT. Side
      effects during and after V-PDT and follow-up results were also analyzed. RESULTS:
      Seven patients with bleeding GI mucosal vascular lesions were treated with V-PDT.
      After 1-4 V-PDT sessions, all patients no longer needed transfusions to maintain
      a stable hemoglobin level during the follow-up period of 6 months. The mean
      hemoglobin level of the seven patients improved from 6.21+/-1.48 g/dl to 11.66+/
      1.21 g/dl (p<0.001), and the GI bleeding and melena of all the patients
      disappeared. No perforations, strictures, scars, or episodes of
      photosensitization occurred in the seven patients, and there were no recurrences
      of GI bleeding during the 1-21 months of further follow-up. CONCLUSIONS: This
      preliminary study indicated that V-PDT is a highly selective, safe, well
      tolerated, and effective treatment modality for bleeding GI mucosal vascular
      lesions. However, prospective studies with larger sample sizes are needed to
      confirm this finding.

PMID- 22594981
TI  - Local clinical phototreatment of herpes infection in Sao Paulo.
AB  - The clinical use of topical photodynamic therapy in herpes simplex lesions in Sao
      Paulo is presented and discussed. Although previous attempts utilising this type
      of approach in the USA were discontinued in the early 1970s due to several
      presentations of post-treatment Bowen's disease, none of the cases from the
      clinic presented here have displayed any complications on follow-up. In addition,
      lesion recrudescence periods are generally much longer than with conventional
      approaches. This is thought to be due to improvements in the treatment protocol,
      viz. use of the non-toxic photosensitisers methylene blue and Hypericum
      perforatum extract in place of proflavine and neutral red in the original trials,
      differences in photosensitisation pathway and illumination of the treatment site
      with red rather than fluorescent/UV light. Post-treatment cosmesis is also
      excellent.

PMID- 22594982
TI  - Antibacterial photodynamic therapy for dental caries: evaluation of the
      photosensitizers used and light source properties.
AB  - Photodynamic therapy studies have shown promising results for inactivation of
      microorganisms related to dental caries. A large number of studies have used a
      variety of protocols, but few studies have analyzed photosensitizers and light
      source properties to obtain the best PDT dose response for dental caries. This
      study aims to discuss the photosensitizers and light source properties employed
      in PDT studies of dental caries. Three questions were formulated to discuss these
      aspects. The first involves the photosensitizer properties and their performance
      against Gram positive and Gram negative bacteria. The second discusses the use of
      light sources in accordance with the dye maximum absorbance to obtain optimal
      results. The third looks at the relevance of photosensitizer concentration, the
      possible formation of self-aggregates, and light source effectiveness. This
      review demonstrated that some groups of photosensitizers may be more effective
      against either Gram positive or negative bacteria, that the light source must be
      appropriate for dye maximum absorbance, and that some photosensitizers may have
      their absorbance modified with their concentration. For the best results of PDT
      against the main cariogenic bacteria (Streptococcus mutans), a variety of aspects
      should be taken into account, and among the analyzed photosensitizer, erythrosin
      seems to be the most appropriate since it acts against this Gram positive
      bacteria, has a hydrophilic tendency and even at low concentrations may have
      photodynamic effects. Considering erythrosin, the most appropriate light source
      should have a maximum emission intensity at a wavelength close to 530 nm, which
      may be achieved with low cost LEDs.

PMID- 22594983
TI  - Elastic scattering spectroscopy in assessing skin lesions: an "in vivo" study.
AB  - INTRODUCTION: Elastic scattering spectroscopy (ESS) has been shown to be accurate
      in the identification of abnormalities of soft tissue. These include ischemia and
      inflammation, pre-cancer and cancer. The aim of this study was to compare
      findings of ESS with gold standard histopathology in patients with various skin
      lesions. MATERIALS AND METHODS: Seventy-three patients with clinically suspicious
      facial skin lesions were included. Those lesions with the surrounding innocuous
      skin were interrogated by ESS, biopsies were taken and examined
      histopathologically; the results were then compared. RESULTS: The preliminary
      analysis showed obvious spectral differences between normal and pathological
      skin. Spectral differences were identified when comparing benign skin conditions
      to malignant ones. Spectral differences were identified between basal cell
      carcinomas and other skin lesions. CONCLUSIONS: This preliminary study shows that
      ESS can distinguish between normal, benign and malignant skin conditions.

PMID- 22594984
TI  - The palliative role of PDT in recurrent advanced nasopharyngeal carcinoma: case
      series.
AB  - We report on the application of photodynamic therapy in the management of
      recurrent advanced carcinoma of the nasopharynx. A selected cohort of 7 patients,
      only suitable for palliative therapy, was offered this modality to assess the
      palliative role of PDT. All 7 patients had at least 2 previous recurrences, which
      were managed with surgery and chemoradiotherapy but ultimately failed to respond.
      PDT was offered after careful discussion at a multidiscipline meeting. The
      photosensitiser "mTHPC" was introduced intravenously 96 h prior to delivering the
      light with nasoendoscopic guidance. Six patients' symptoms were reduced markedly
      post photodynamic therapy. Five patients have to had another round of treatment
      which was found to be as effective as the first round in terms of controlling
      disease progression as well as symptoms. Magnetic resonance images showed
      variable reduction of tumour volume with the majority of the patients having
      moderate to significant response. Photodynamic therapy was very successful
      palliative therapy for this small group of recurrent advanced nasopharyngeal
      cancer patients.

PMID- 22594985
TI  - Comparison of cryotherapy and photodynamic therapy in treatment of oral
      leukoplakia.
AB  - Oral leukoplakia is a pre-malignant lesion of the oral mucosa. The aim of this
      study is to compare the curative effects of photodynamic therapy and cryotherapy
      in the treatment of oral leukoplakia. The first group, treated by photodynamic
      therapy (delta-aminolevulinic acid (ALA), 630-635 nm wavelength), consisted of 48
      patients suffering from leukoplakia. The second group consisted of 37 patients
      treated using cryotherapy. Analyses and comparisons of the complete responses,
      recurrences, numbers of procedures and adverse effects after both PDT and
      cryotherapy were obtained. In the first group, a complete response was obtained
      in 35 patients (72.9%), with thirteen recurrences observed (27.1%) over a six
      month period. In the second group, a complete response was obtained in 33
      patients (89.2%), and recurrence was observed in nine patients (24.3%).
      Photodynamic therapy and cryotherapy appear to be comparative methods of
      treatment that may both serve as alternatives for the traditional surgical
      treatment of oral leukoplakia. The advantages of PDT are connected with minimally
      invasive and localized character of the treatment and with not damage of
      collagenous tissue structures, therefore normal cells will repopulate these
      arrangements. PDT is more convenient for patients, less painful, and more
      esthetic.

PMID- 22594986
TI  - Depigmentation in melanomas increases the efficacy of hypericin-mediated
      photodynamic-induced cell death.
AB  - Melanoma is the main cause of death in skin cancers. Despite combating with early
      detection, resection and post-operative therapy, melanoma treatment remains
      unsuccessful and investigations into other forms of adjuvant therapy such as
      photodynamic therapy (PDT) are prudent. This study proposes that depigmentation
      i.e. the removal of the free radical scavenging pigment, melanin, in melanotic
      melanoma cells increases their susceptibility to PDT-induced cell death. Two
      human melanoma cell lines: one pigmented (Mel-1) and one amelanotic (A(375)) cell
      lines were used. Kojic acid (KA), a tyrosinase-specific inhibitor, was optimised
      to 6 MUg/ml and shown to quantifiably inhibit melanin synthesis after a 3-day
      exposure. PDT on these cells resulted in a 3.82 fold increase of intracellular
      ROS production which correlated to 11% increase in cell death susceptibility
      compared to untreated controls. Moreover, cells allowed to regain their pigment
      failed to return to normal even after 72 h thus proving the effectiveness of PDT.
      Using a DPPH* assay, the results confirmed the scavenging properties of melanin
      (IC(50) 18.30 MUg/ml) proving that this pigment may be one of the reasons for
      melanoma chemoresistance. Overall this study shows that pigment plays an
      important role in the efficacy of adjunctive PDT treatment and its removal
      enhances cell death susceptibility in melanomas.

PMID- 22594987
TI  - Evaluation of collagen alteration after topical photodynamic therapy (PDT) using
      second harmonic generation (SHG) microscopy--in vivo study in a mouse model.
AB  - Topical photodynamic therapy (PDT) mediated by 5-aminolevulinic acid (ALA) has
      been used for the treatment of age-related skin lesions for therapeutic or
      cosmetic purposes. The modulation of collagen component and structure might play
      a significant role in influencing treatment outcomes of PDT. In this study, the
      effect of multi-session low dose ALA PDT on skin rejuvenation was examined in a
      hairless mouse model. Changes in collagen and skin texture were investigated by
      histological examination and in vivo second harmonic generation (SHG) microscopy.
      Results indicated that multi-session PDT could improve the collagen density and
      arrangement of skin tissue. SHG microscopy combined with quantitative collagen
      analysis could provide a useful tool for the evaluation of collagen alteration
      induced by ALA PDT.

PMID- 22594988
TI  - mTHPC--a drug on its way from second to third generation photosensitizer?
AB  - 5,10,15,20-Tetrakis(3-hydroxyphenyl)chlorin (mTHPC, Temoporfin) is a widely
      investigated second generation photosensitizer. Its initial use in solution form
      (Foscan(r)) is now complemented by nanoformulations (Fospeg(r), Foslip(r)) and
      new chemical derivatives related to the basic hydroxyphenylporphyrin framework.
      Advances in formulation, chemical modifications and targeting strategies open the
      way for third generation photosensitizers and give an illustrative example for
      the developmental process of new photoactive drugs.

PMID- 22594989
TI  - Research progress of Hemoporfin--part one: preclinical study.
AB  - The second generation photosensitizer Hemoporfin (7(12)-(1-methoxyethyl) -12(7)
      (1-hydroxyethyl)-3,8,13,17-tetramethyl-21H,23H-porphin-2,18-dipropionic acid) is
      a porphyrin derivative which processes a stable structure, high singlet oxygen
      yield, high photoactivity, low dark toxicity and fast clearance rate. Hemoporfin,
      also known as hematoporphyrin monomethyl ether (HMME) has been studied and used
      in photodynamic therapy (PDT) in China since 1989. This series of reports will
      provide an overview on the preclinical and clinical studies of this PDT
      photosensitizer. The first part of this series will highlight the results of
      preclinical studies that focused on the compound's optical characteristics,
      mechanism of the activities, pharmacological and toxicological properties.

PMID- 22594990
TI  - Photodynamic therapy of vulvar lichen sclerosus et atrophicus in a woman with
      hypothyreosis--case report.
AB  - Lichen sclerosus et atrophicus (LSA) is disease of skin and mucosa, its
      pathogenesis remains unknown. Itching, pain and burning sensations and atrophy of
      vulva impair quality of life. Treatment is symptomatic. We report case of 30-year
      old woman with lesions in vulva in which series of topical PDT were carried out.
      We applied Levulan(r)Kerastick(r) for 4h and after that lesions were illuminated
      with red light. Along with above treatment patient started receiving Euthyrox(r),
      because of recently diagnosed hypothyreosis. Significant relief from subjective
      symptoms was achieved and lesions in vulvar region disappeared. Combination of
      topical PDT with hormonal therapy allowed controlling course of disease and
      minimizing symptoms, and thus improved quality of life.

PMID- 22594991
TI  - Secondary focal and segmental glomerulosclerosis associated with single
      nucleotide polymorphisms in the genes encoding complement factor H and C3.
AB  - Genetic causes of focal and segmental glomerulosclerosis (FSGS) typically involve
      mutations and allele variants of genes expressed in podocytes or, more rarely,
      glomerular basement membranes. In this report, we describe a 60-year-old woman
      with chronic kidney disease whose kidney biopsy showed FSGS. Immunoglobulins and
      C3 were undetectable in immunofluorescence studies. Electron microscopy showed
      subendothelial fluffy granular material with occasional double-contour formation
      suggestive of capillary wall injury and prompting work-up for a prothrombotic
      state. Evaluation of the alternative pathway of complement showed a novel
      polymorphism in short consensus repeat (SCR) 12 of complement factor H (CFH;
      c.2195C>T, p.Thr732Met) and a previously reported but largely uncharacterized
      polymorphism in complement factor C3 (c.463A>C, p.Lys155Gln). Dysregulation of
      the alternative pathway is associated with atypical hemolytic syndrome and dense
      deposit disease, but heretofore has not been associated with FSGS. This case
      highlights the expanding spectrum of complement-mediated glomerular disease and
      shows that FSGS with features of capillary wall injury should prompt evaluation
      for abnormalities in the alternative pathway. This case also expands the list of
      genetic polymorphisms that can be associated with an FSGS phenotype.

PMID- 22594992
TI  - Interleukin-4 polymorphisms and response to combination therapy in Egyptian
      chronic hepatitis C patients.
AB  - In hepatitis C infection, the production of inappropriate cytokines levels may
      contribute to viral persistence and may affect the response to antiviral therapy.
      We investigate the effect of IL4 C-590T and C-33T polymorphisms on the response
      to combination therapy with interferon and ribavirin in chronic HCV patients.
      These single nucleotide polymorphisms were determined by PCR-RFLP in 235
      responder and 210 non-responder to combination therapy. The IL4-590 T/T and -33
      T/T genotypes were associated with resistance to the therapy (p<0.001, p=0.001
      respectively). Haplotypes T(-590) T(-33) and T(-590) C(-33) were associated with
      a higher risk in non-responder patients than the responders (p<0.001 for each)
      while frequency of haplotype C(-590) C(-33) (with all wild alleles) was
      significantly higher in responders as compared to non-responders (p<0.001). These
      results suggest that inheritance of the IL4 polymorphisms may be associated with
      resistance to combined antiviral therapy in Egyptian HCV patients.

PMID- 22594993
TI  - Cytomegalovirus replication kinetics in solid organ transplant recipients managed
      by preemptive therapy.
AB  - After allotransplantation, cytomegalovirus (CMV) may be transmitted from the
      donor organ, giving rise to primary infection in a CMV negative recipient or
      reinfection in one who is CMV positive. In addition, latent CMV may reactivate in
      a CMV positive recipient. In this study, serial blood samples from 689 kidney or
      liver transplant recipients were tested for CMV DNA by quantitative PCR. CMV was
      managed using preemptive antiviral therapy and no patient received antiviral
      prophylaxis. Dynamic and quantitative measures of viremia and treatment were
      assessed. Median peak viral load, duration of viremia and duration of treatment
      were highest during primary infection, followed by reinfection then reactivation.
      In patients who experienced a second episode of viremia, the viral replication
      rate was significantly slower than in the first episode. Our data provide a clear
      demonstration of the immune control of CMV in immunosuppressed patients and
      emphasize the effectiveness of the preemptive approach for prevention of CMV
      syndrome and end organ disease. Overall, our findings provide quantitative
      biomarkers which can be used in pharmacodynamic assessments of the ability of
      novel CMV vaccines or antiviral drugs to reduce or even interrupt such
      transmission.

PMID- 22594994
TI  - Introduction: Advanced intelligent computing theories and their applications in
      bioinformatics.

PMID- 22594995
TI  - Relationship between amino acid properties and functional parameters in olfactory
      receptors and discrimination of mutants with enhanced specificity.
AB  - BACKGROUND: Olfactory receptors are key components in signal transduction.
      Mutations in olfactory receptors alter the odor response, which is a fundamental
      response of organisms to their immediate environment. Understanding the
      relationship between odorant response and mutations in olfactory receptors is an
      important problem in bioinformatics and computational biology. In this work, we
      have systematically analyzed the relationship between various physical, chemical,
      energetic and conformational properties of amino acid residues, and the change of
      odor response/compound's potency/half maximal effective concentration (EC50) due
      to amino acid substitutions. RESULTS: We observed that both the characteristics
      of odorant molecule (ligand) and amino acid properties are important for odor
      response and EC50. Additional information on neighboring and surrounding residues
      of the mutants enhanced the correlation between amino acid properties and EC50.
      Further, amino acid properties have been combined systematically using multiple
      regression techniques and we obtained a correlation of 0.90-0.98 with odor
      response/EC50 of goldfish, mouse and human olfactory receptors. In addition, we
      have utilized machine learning methods to discriminate the mutants, which enhance
      or reduce EC50 values upon mutation and we obtained an accuracy of 93% and 79%
      for self-consistency and jack-knife tests, respectively. CONCLUSIONS: Our
      analysis provides deep insights for understanding the odor response of olfactory
      receptor mutants and the present method could be used for identifying the mutants
      with enhanced specificity.

PMID- 22594996
TI  - Modeling the interactions of Alzheimer-related genes from the whole brain
      microarray data and diffusion tensor images of human brain.
AB  - BACKGROUND: In recent years the genome-wide microarray-based gene expression
      profiles and diffusion tensor images (DTI) in human brain have been made
      available with accompanying anatomic and histology data. The challenge is to
      integrate various types of data to investigate the interactions of genes that are
      associated with specific neurological disorder. RESULTS: In this study, we
      analyzed the whole brain microarray data and the physical connectivity of the
      hippocampus with other brain regions to identify the genes related to Alzheimer's
      disease and their interactions with proteins. We generated a physical
      connectivity map of the left and right hippocampuses with 12 other brain regions
      and identified 33 Alzheimer-related genes that interact with many proteins. These
      genes are highly linked to the development of Alzheimer's disease. CONCLUSIONS:
      In Alzheimer's brain both brain regions and inter-regional communications through
      the white matter are often hampered. So far the connectivity of regions in
      Alzheimer's brain has been studied mostly at the functional level using
      functional MRI (fMRI). Analyzing the inter-regional fiber connectivity without
      tracking crossing-fiber regions often provides coarse and inaccurate results. A
      few deep brain fibers were analyzed but the inter-regional fiber connectivity was
      not analyzed in their studies. The inter-regional fiber connectivity analysis can
      provide comprehensive and measurable degradation of fiber tracts in AD patients'
      brains, but is not easy to perform. We tracked crossing-fiber regions and
      identified genes with high expression levels in the fiber pathways of the
      hippocampus. The interactions of the genes with other proteins can provide
      comprehensive and measurable degradation of fiber tracts in Alzheimer brains. To
      the best of our knowledge, this is the first attempt to integrate the whole brain
      microarray data with DTI data to identify specific genes and their interactions.

PMID- 22594997
TI  - Pattern-driven neighborhood search for biclustering of microarray data.
AB  - BACKGROUND: Biclustering aims at finding subgroups of genes that show highly
      correlated behaviors across a subgroup of conditions. Biclustering is a very
      useful tool for mining microarray data and has various practical applications.
      From a computational point of view, biclustering is a highly combinatorial search
      problem and can be solved with optimization methods. RESULTS: We describe a
      stochastic pattern-driven neighborhood search algorithm for the biclustering
      problem. Starting from an initial bicluster, the proposed method improves
      progressively the quality of the bicluster by adjusting some genes and
      conditions. The adjustments are based on the quality of each gene and condition
      with respect to the bicluster and the initial data matrix. The performance of the
      method was evaluated on two well-known microarray datasets (Yeast cell cycle and
      Saccharomyces cerevisiae), showing that it is able to obtain statistically and
      biologically significant biclusters. The proposed method was also compared with
      six reference methods from the literature. CONCLUSIONS: The proposed method is
      computationally fast and can be applied to discover significant biclusters. It
      can also used to effectively improve the quality of existing biclusters provided
      by other biclustering methods.

PMID- 22594998
TI  - Genovar: a detection and visualization tool for genomic variants.
AB  - BACKGROUND: Along with single nucleotide polymorphisms (SNPs), copy number
      variation (CNV) is considered an important source of genetic variation associated
      with disease susceptibility. Despite the importance of CNV, the tools currently
      available for its analysis often produce false positive results due to
      limitations such as low resolution of array platforms, platform specificity, and
      the type of CNV. To resolve this problem, spurious signals must be separated from
      true signals by visual inspection. None of the previously reported CNV analysis
      tools support this function and the simultaneous visualization of comparative
      genomic hybridization arrays (aCGH) and sequence alignment. The purpose of the
      present study was to develop a useful program for the efficient detection and
      visualization of CNV regions that enables the manual exclusion of erroneous
      signals. RESULTS: A JAVA-based stand-alone program called Genovar was developed.
      To ascertain whether a detected CNV region is a novel variant, Genovar compares
      the detected CNV regions with previously reported CNV regions using the Database
      of Genomic Variants (DGV, http://projects.tcag.ca/variation) and the Single
      Nucleotide Polymorphism Database (dbSNP). The current version of Genovar is
      capable of visualizing genomic data from sources such as the aCGH data file and
      sequence alignment format files. CONCLUSIONS: Genovar is freely accessible and
      provides a user-friendly graphic user interface (GUI) to facilitate the detection
      of CNV regions. The program also provides comprehensive information to help in
      the elimination of spurious signals by visual inspection, making Genovar a
      valuable tool for reducing false positive CNV results. AVAILABILITY:
      http://genovar.sourceforge.net/.

PMID- 22594999
TI  - ProDis-ContSHC: learning protein dissimilarity measures and hierarchical context
      coherently for protein-protein comparison in protein database retrieval.
AB  - BACKGROUND: The need to retrieve or classify protein molecules using structure or
      sequence-based similarity measures underlies a wide range of biomedical
      applications. Traditional protein search methods rely on a pairwise
      dissimilarity/similarity measure for comparing a pair of proteins. This kind of
      pairwise measures suffer from the limitation of neglecting the distribution of
      other proteins and thus cannot satisfy the need for high accuracy of the
      retrieval systems. Recent work in the machine learning community has shown that
      exploiting the global structure of the database and learning the contextual
      dissimilarity/similarity measures can improve the retrieval performance
      significantly. However, most existing contextual dissimilarity/similarity
      learning algorithms work in an unsupervised manner, which does not utilize the
      information of the known class labels of proteins in the database. RESULTS: In
      this paper, we propose a novel protein-protein dissimilarity learning algorithm,
      ProDis-ContSHC. ProDis-ContSHC regularizes an existing dissimilarity measure dij
      by considering the contextual information of the proteins. The context of a
      protein is defined by its neighboring proteins. The basic idea is, for a pair of
      proteins (i, j), if their context N(i) and N(j) is similar to each other, the two
      proteins should also have a high similarity. We implement this idea by
      regularizing dij by a factor learned from the context N(i) and N(j).Moreover, we
      divide the context to hierarchial sub-context and get the contextual
      dissimilarity vector for each protein pair. Using the class label information of
      the proteins, we select the relevant (a pair of proteins that has the same class
      labels) and irrelevant (with different labels) protein pairs, and train an SVM
      model to distinguish between their contextual dissimilarity vectors. The SVM
      model is further used to learn a supervised regularizing factor. Finally, with
      the new Supervised learned Dissimilarity measure, we update the Protein
      Hierarchial Context Coherently in an iterative algorithm--ProDis-ContSHC.We test
      the performance of ProDis-ContSHC on two benchmark sets, i.e., the ASTRAL 1.73
      database and the FSSP/DALI database. Experimental results demonstrate that
      plugging our supervised contextual dissimilarity measures into the retrieval
      systems significantly outperforms the context-free dissimilarity/similarity
      measures and other unsupervised contextual dissimilarity measures that do not use
      the class label information. CONCLUSIONS: Using the contextual proteins with
      their class labels in the database, we can improve the accuracy of the pairwise
      dissimilarity/similarity measures dramatically for the protein retrieval tasks.
      In this work, for the first time, we propose the idea of supervised contextual
      dissimilarity learning, resulting in the ProDis-ContSHC algorithm. Among
      different contextual dissimilarity learning approaches that can be used to
      compare a pair of proteins, ProDis-ContSHC provides the highest accuracy.
      Finally, ProDis-ContSHC compares favorably with other methods reported in the
      recent literature.

PMID- 22595000
TI  - Assessing and predicting protein interactions by combining manifold embedding
      with multiple information integration.
AB  - BACKGROUND: Protein-protein interactions (PPIs) play crucial roles in virtually
      every aspect of cellular function within an organism. Over the last decade, the
      development of novel high-throughput techniques has resulted in enormous amounts
      of data and provided valuable resources for studying protein interactions.
      However, these high-throughput protein interaction data are often associated with
      high false positive and false negative rates. It is therefore highly desirable to
      develop scalable methods to identify these errors from the computational
      perspective. RESULTS: We have developed a robust computational technique for
      assessing the reliability of interactions and predicting new interactions by
      combining manifold embedding with multiple information integration. Validation of
      the proposed method was performed with extensive experiments on densely-connected
      and sparse PPI networks of yeast respectively. Results demonstrate that the
      interactions ranked top by our method have high functional homogeneity and
      localization coherence. CONCLUSIONS: Our proposed method achieves better
      performances than the existing methods no matter assessing or predicting protein
      interactions. Furthermore, our method is general enough to work over a variety of
      PPI networks irrespectively of densely-connected or sparse PPI network.
      Therefore, the proposed algorithm is a much more promising method to detect both
      false positive and false negative interactions in PPI networks.

PMID- 22595001
TI  - An overlapping module identification method in protein-protein interaction
      networks.
AB  - BACKGROUND: Previous studies have shown modular structures in PPI (protein
      protein interaction) networks. More recently, many genome and metagenome
      investigations have focused on identifying modules in PPI networks. However, most
      of the existing methods are insufficient when applied to networks with
      overlapping modular structures. In our study, we describe a novel overlapping
      module identification method (OMIM) to address this problem. RESULTS: Our method
      is an agglomerative clustering method merging modules according to their
      contributions to modularity. Nodes that have positive effects on more than two
      modules are defined as overlapping parts. As well, we designed de-noising steps
      based on a clustering coefficient and hub finding steps based on nodal weight.
      CONCLUSIONS: The low computational complexity and few control parameters prove
      that our method is suitable for large scale PPI network analysis. First, we
      verified OMIM on a small artificial word association network which was able to
      provide us with a comprehensive evaluation. Then experiments on real PPI networks
      from the MIPS Saccharomyces Cerevisiae dataset were carried out. The results show
      that OMIM outperforms several other popular methods in identifying high quality
      modular structures.

PMID- 22595002
TI  - Prediction of protein-protein interactions between viruses and human by an SVM
      model.
AB  - BACKGROUND: Several computational methods have been developed to predict protein
      protein interactions from amino acid sequences, but most of those methods are
      intended for the interactions within a species rather than for interactions
      across different species. Methods for predicting interactions between homogeneous
      proteins are not appropriate for finding those between heterogeneous proteins
      since they do not distinguish the interactions between proteins of the same
      species from those of different species. RESULTS: We developed a new method for
      representing a protein sequence of variable length in a frequency vector of fixed
      length, which encodes the relative frequency of three consecutive amino acids of
      a sequence. We built a support vector machine (SVM) model to predict human
      proteins that interact with virus proteins. In two types of viruses, human
      papillomaviruses (HPV) and hepatitis C virus (HCV), our SVM model achieved an
      average accuracy above 80%, which is higher than that of another SVM model with a
      different representation scheme. Using the SVM model and Gene Ontology (GO)
      annotations of proteins, we predicted new interactions between virus proteins and
      human proteins. CONCLUSIONS: Encoding the relative frequency of amino acid
      triplets of a protein sequence is a simple yet powerful representation method for
      predicting protein-protein interactions across different species. The
      representation method has several advantages: (1) it enables a prediction model
      to achieve a better performance than other representations, (2) it generates
      feature vectors of fixed length regardless of the sequence length, and (3) the
      same representation is applicable to different types of proteins.

PMID- 22595003
TI  - Inferring a protein interaction map of Mycobacterium tuberculosis based on
      sequences and interologs.
AB  - BACKGROUND: Mycobacterium tuberculosis is an infectious bacterium posing serious
      threats to human health. Due to the difficulty in performing molecular biology
      experiments to detect protein interactions, reconstruction of a protein
      interaction map of M. tuberculosis by computational methods will provide crucial
      information to understand the biological processes in the pathogenic
      microorganism, as well as provide the framework upon which new therapeutic
      approaches can be developed. RESULTS: In this paper, we constructed an integrated
      M. tuberculosis protein interaction network by machine learning and ortholog
      based methods. Firstly, we built a support vector machine (SVM) method to infer
      the protein interactions of M. tuberculosis H37Rv by gene sequence information.
      We tested our predictors in Escherichia coli and mapped the genetic codon
      features underlying its protein interactions to M. tuberculosis. Moreover, the
      documented interactions of 14 other species were mapped to the interactome of M.
      tuberculosis by the interolog method. The ensemble protein interactions were
      validated by various functional relationships, i.e., gene coexpression,
      evolutionary relationship and functional similarity, extracted from heterogeneous
      data sources. The accuracy and validation demonstrate the effectiveness and
      efficiency of our framework. CONCLUSIONS: A protein interaction map of M.
      tuberculosis is inferred from genetic codons and interologs. The prediction
      accuracy and numerically experimental validation demonstrate the effectiveness
      and efficiency of our method. Furthermore, our methods can be straightforwardly
      extended to infer the protein interactions of other bacterial species.

PMID- 22595004
TI  - Exploring drug combinations in genetic interaction network.
AB  - BACKGROUND: Drug combination that consists of distinctive agents is an attractive
      strategy to combat complex diseases and has been widely used clinically with
      improved therapeutic effects. However, the identification of efficacious drug
      combinations remains a non-trivial and challenging task due to the huge number of
      possible combinations among the candidate drugs. As an important factor, the
      molecular context in which drugs exert their functions can provide crucial
      insights into the mechanism underlying drug combinations. RESULTS: In this work,
      we present a network biology approach to investigate drug combinations and their
      target proteins in the context of genetic interaction networks and the related
      human pathways, in order to better understand the underlying rules of effective
      drug combinations. Our results indicate that combinatorial drugs tend to have a
      smaller effect radius in the genetic interaction networks, which is an important
      parameter to describe the therapeutic effect of a drug combination from the
      network perspective. We also find that drug combinations are more likely to
      modulate functionally related pathways. CONCLUSIONS: This study confirms that the
      molecular networks where drug combinations exert their functions can indeed
      provide important insights into the underlying rules of effective drug
      combinations. We hope that our findings can help shortcut the expedition of the
      future discovery of novel drug combinations.

PMID- 22595005
TI  - Inferring robust gene networks from expression data by a sensitivity-based
      incremental evolution method.
AB  - BACKGROUND: Reconstructing gene regulatory networks (GRNs) from expression data
      is one of the most important challenges in systems biology research. Many
      computational models and methods have been proposed to automate the process of
      network reconstruction. Inferring robust networks with desired behaviours remains
      challenging, however. This problem is related to network dynamics but has yet to
      be investigated using network modeling. RESULTS: We propose an incremental
      evolution approach for inferring GRNs that takes network robustness into
      consideration and can deal with a large number of network parameters. Our
      approach includes a sensitivity analysis procedure to iteratively select the most
      influential network parameters, and it uses a swarm intelligence procedure to
      perform parameter optimization. We have conducted a series of experiments to
      evaluate the external behaviors and internal robustness of the networks inferred
      by the proposed approach. The results and analyses have verified the
      effectiveness of our approach. CONCLUSIONS: Sensitivity analysis is crucial to
      identifying the most sensitive parameters that govern the network dynamics. It
      can further be used to derive constraints for network parameters in the network
      reconstruction process. The experimental results show that the proposed approach
      can successfully infer robust GRNs with desired system behaviors.

PMID- 22595006
TI  - Comparison of data-merging methods with SVM attribute selection and
      classification in breast cancer gene expression.
AB  - BACKGROUND: DNA microarray data are used to identify genes which could be
      considered prognostic markers. However, due to the limited sample size of each
      study, the signatures are unstable in terms of the composing genes and may be
      limited in terms of performances. It is therefore of great interest to integrate
      different studies, thus increasing sample size. RESULTS: In the past, several
      studies explored the issue of microarray data merging, but the arrival of new
      techniques and a focus on SVM based classification needed further investigation.
      We used distant metastasis prediction based on SVM attribute selection and
      classification to three breast cancer data sets. CONCLUSIONS: The results showed
      that breast cancer classification does not benefit from data merging, confirming
      the results found by other studies with different techniques.

PMID- 22595007
TI  - Polycyclic pi-electron system with boron at its center.
AB  - We disclose a new planarized triarylborane in which the tri-coordinated boron
      atom is embedded in a fully fused polycyclic pi-conjugated skeleton. The compound
      shows high stability toward oxygen, water, and silica gel, despite the absence of
      steric protection around the B atom. Reflecting the electron-donating character
      of the pi-skeleton and the electron-accepting character of the B atom, this
      compound shows broad absorption bands that cover the entire visible region and a
      fluorescence in the visible/near-IR region. In addition, this compound shows
      dramatic property changes upon formation of a tetra-coordinated borate, such as
      thermochromic behavior in the presence of pyridine.

PMID- 22595008
TI  - Cations in charge: magnesium ions in RNA folding and catalysis.

PMID- 22595009
TI  - Restoring sinus rhythm: a novel antihypertensive therapy?

PMID- 22595010
TI  - Modulators of Na/K-ATPase: a patent review.
AB  - INTRODUCTION: Na/K-ATPase is a heterodimeric transmembrane protein that regulates
      neuronal signaling, ion homeostasis, muscle contraction and substrate
      transportation. Modulators of Na/K-ATPase inhibit Na(+)/K(+) exchange and
      increase cytosolic Ca(2+) to induce inotropic activity in heart failure patients.
      Besides producing inotropic effects, the Na/K-ATPase acts as a signal transducer
      for the regulation of many cellular events, including those associated with tumor
      cell growth. This has aroused new interest for development of Na/K-ATPase
      inhibitors as anticancer agents. AREAS COVERED: This article summarizes the
      various Na/K-ATPase inhibitors that have shown biological importance in clinical
      study and drug development for inotropic and anticancer agents. EXPERT OPINION:
      The field of Na/K-ATPase modulators has attracted much interest in the past
      because of their clinical implication in heart failure treatments. Recent studies
      have shown that Na/K-ATPase modulators are capable of producing profound
      anticancer effects upon binding to the Na/K-ATPase. Interestingly, certain Na/K
      ATPase isoforms are highly expressed in particular cancer cells, providing the
      opportunity for a Na/K-ATPase modulator to selectively target these cellular
      abnormalities. Indeed the most well-known Na/K-ATPase modulators, cardiac
      glycosides, have shown both strong binding affinity and moderate selectivity for
      isoforms. It is anticipated, in the future, that the further development of more
      selective and potent Na/K-ATPase modulators will take place, which in turn could
      lead to a more effective treatment for either heart failure or cancer.

PMID- 22595011
TI  - Advances in the pathology of penile carcinomas.
AB  - The incidence of penile cancer varies from country to country, with the highest
      figures reported for countries in Africa, South America, and Asia and lowest in
      the United States and Europe. Causes of this variation are not clear, but they
      are thought to be related to human papillomavirus infection, smoking, lack of
      circumcision, chronic inflammation, and poor genital hygiene. Most penile tumors
      are squamous cell carcinomas, and a variegated spectrum of distinct morphologies
      is currently recognized. Each one of these subtypes has distinctive pathologic
      and clinical features. About half of penile carcinomas are usual squamous cell
      carcinomas, and the rest corresponds to verrucous, warty, basaloid, warty
      basaloid, papillary, pseudohyperplastic, pseudoglandular, adenosquamous,
      sarcomatoid, and cuniculatum carcinomas. Previous studies have found a consistent
      association of tumor cell morphology and human papillomavirus presence in penile
      carcinomas. Those tumors composed of small- to intermediate-sized, basaloid
      ("blue") cells are often human papillomavirus positive, whereas human
      papillomavirus prevalence is lower in tumors showing large, keratinizing,
      maturing eosinophilic ("pink") cells. Human papillomavirus-related tumors affect
      younger patients, whereas human papillomavirus-unrelated tumors are seen in older
      patients with phimosis, lichen sclerosus, or squamous hyperplasia. This
      morphologic distinctiveness is also observed in penile intraepithelial neoplasia.
      The specific aim of this review is to provide a detailed discussion on the
      macroscopic and microscopic features of all major subtypes of penile cancer. We
      also discuss the role of pathologic features in the prognosis of penile cancer,
      the characteristics of penile precursor lesions, and the use of
      immunohistochemistry for the diagnosis of invasive and precursor lesions.

PMID- 22595012
TI  - Ultraviolet radiation resistance-associated polyadenine deletions in human
      gastric cancer.

PMID- 22595013
TI  - The feature-binding problem is an ill-posed problem.
AB  - The binding problem arises when visual features (colour, orientation), said to be
      coded in independent brain modules, are to be integrated into unitary percepts. I
      argue that binding is an ill-posed problem, because those modules are now known
      to code jointly for multiple features, rendering the feature-binding issue moot.
      A hierarchical reentrant system explains the emergence of coherent visual objects
      from primitive features. An initial feed-forward sweep activates many high-level
      perceptual hypotheses, which descend to lower levels, where they correlate
      themselves with the ongoing activity. Low correlations are discarded, whereas the
      hypothesis that yields the highest correlation is confirmed and leads to
      conscious awareness. In this system, there is no separate binding process that
      actively assigns features to objects.

PMID- 22595014
TI  - [Fungal endocarditis with central and peripheral embolization: case report].
AB  - A 50-year-old man with a history of drug addiction was admitted to the cardiology
      department for aortic valve fungal endocarditis complicated by severe aortic
      regurgitation, cerebral infarcts and right common iliac artery pseudoaneurysm.
      While awaiting transfer to the cardiothoracic surgery department, the patient
      presented acute arterial ischemia of the left leg, and distal left patellofemoral
      embolectomy was successfully performed. The patient was then transferred to the
      cardiothoracic center and the aortic valve was replaced by a bioprosthetic valve.
      After fourteen days he was referred for vascular surgery, where the four-month
      hospitalization was complicated by left leg amputation. Four months after
      discharge, the patient was admitted to the emergency department for recurrent
      fungal endocarditis complicated by multiple renal and splenic infarcts and celiac
      trunk embolization. He was transferred to the cardiothoracic surgery department,
      but suffered cardiac arrest before surgical intervention.

PMID- 22595015
TI  - Neutrophil elastase inhibitor improves survival rate after ischemia reperfusion
      injury caused by supravisceral aortic clamping in rats.
AB  - BACKGROUND: Sivelestat sodium hydrate is a specific neutrophil elastase inhibitor
      effective in acute lung injury (ALI) associated with systemic inflammatory
      response syndrome. Bowel ischemia reperfusion injury (IRI) induced by
      supravisceral aortic clamping is associated with an excessive systemic
      inflammatory response, resulting in remote organ damage, including ALI. In this
      study, we investigated whether sivelestat can attenuate neutrophil sequestration
      in the lung, alleviate ALI, and improve survival in a rat bowel IRI model.
      METHODS: Adult male Sprague-Dawley rats underwent bowel IRI induced by
      supravisceral aortic clamping and were randomly assigned to receive sivelestat or
      saline (control) and monitored for survival. We randomly assigned other rats to
      undergo laparotomy alone (sham operation), IRI alone, or IRI and sivelestat
      treatment. We evaluated blood samples for organ function, cytokine levels, and
      neutrophil elastase activity after reperfusion. Organs were analyzed
      histologically. We also determined lung injury in another set of rats. RESULTS:
      Bowel IRI induced a significant increase in serum variables indicative of organ
      function, cytokine concentrations, neutrophil elastase activity, and lung
      permeability and edema, which reflected the presence of both systemic
      inflammatory response syndrome and compensatory anti-inflammatory response
      syndrome. Treatment with sivelestat significantly improved survival rate, lung
      permeability and edema, and significantly decreased levels of creatinine,
      interleukin 6, interleukin 10, and neutrophil elastase activity. Histological
      studies showed that sivelestat-treated rats had less bowel IRI-induced damage to
      lung and liver tissue than controls. CONCLUSION: In a rat model, administration
      of sivelestat attenuated the effects of bowel IRI induced by supravisceral aortic
      clamping, and improved the survival rate.

PMID- 22595016
TI  - The effects of irrigation on outcomes in cases of perforated appendicitis in
      children.
AB  - INTRODUCTION: Appendicitis is the most common indication for urgent abdominal
      operation in children. Approximately 20%-30% of patients will have a perforation
      at operation. Intra-abdominal abscess after appendectomy is reported in 3%-20% of
      patients and adds significantly to hospital stay with increased morbidity and
      overall cost. Surgical dogma has long advocated for irrigation in the setting of
      gross pus to prevent abscess formation. METHODS: Following IRB approval, data
      were retrospectively collected for children who had undergone appendectomy for
      perforated appendicitis at one of two children's hospitals over the course of 5
      y. Perforation was determined by review of operative notes. All patients had free
      fluid in their peritoneal cavity evacuated by suction, whereas some of the
      patients also had their peritoneal cavity irrigated with normal saline.
      Postoperative intra-abdominal abscess rates were determined based on clinical
      symptoms and confirmatory radiologic studies. RESULTS: There were 99 patients in
      the suction-only group and 139 in the irrigation group. Standard demographics
      were relatively similar between the two groups. There were significantly lower
      rates of intra-abdominal abscess formation (4.0% versus 17.2%, P = 0.002) and
      wound infection (1.0% versus 8.6%, P = 0.003) in the suction-only group compared
      with the irrigation group. We further analyzed abscess rates by surgical
      treatment, either laparoscopic or open appendectomy. There were 85 patients in
      the laparoscopic group and 152 patients in the open appendectomy group. In this
      subgroup analysis, there were also significantly lower rates of abscess formation
      in patients treated with suction only compared with irrigation in the
      laparoscopic (3.5% versus 18.8%, P = 0.012) and open appendectomy groups (4.2%
      versus 16.3%, P = 0.036). CONCLUSIONS: Results of this retrospective review
      indicate that a suction-only approach significantly decreased rates of abscess
      formation and wound infections compared to irrigation in cases of perforated
      appendicitis in children.

PMID- 22595017
TI  - Galphaq G proteins modulate MMP-9 gelatinase during remodeling of the murine
      femoral artery.
AB  - BACKGROUND: Vessels heal after injury and G protein-coupled receptors are
      involved in the vascular smooth muscle cell proliferation required to form
      intimal hyperplasia. We have previously identified the role of Galphaq in
      vascular smooth muscle cell proliferation in vitro. This study now examines the
      role of Galphaq in the developing intimal hyperplasia in a murine model and the
      impact of disruption of Galphaq signaling on intimal hyperplasia development.
      METHODS: We employed a murine femoral wire injury model in which a micro-wire is
      passed through a branch of the femoral artery and used to denude the common
      femoral artery. We perfusion-fixed specimens and stained sections with
      hematoxylin-eosin and Movat's stains such that morphometric analysis could be
      performed using an Image-Pro system. We also harvested additional specimens of
      femoral artery and snap-froze them for Western blotting or zymography, to allow
      for the study of G protein expression and both protease expression and activity.
      We used contralateral vessels as controls. We immersed additional vessels in
      pluronic gel containing the chemical Galphaq G protein inhibitors GP-2A, siRNA to
      Galphaq or adenovirus containing mutant inactive Galphaq. RESULTS: Galphaq
      expression increased in a time-dependent manner after femoral artery injury. Sham
      operated vessels did not produce such a response. Inhibition of Galphaq reduced
      cell proliferation without affecting cell migration. Interruption of Galphaq
      signaling also inhibited the development of intimal hyperplasia. Inhibition of
      Galphaq did not alter peak urinary-type plasminogen activator activity and
      expression, but did increase early plasminogen activator inhibitor-1 activity and
      expression. Inhibition of Galphaq reduced peak metalloproteinase (MMP)-9 activity
      at Day 3 but did not influence peak MMP-2 activity at Day 7. Protein expression
      for MMP-9 was also decreased, but that of MMP-2 was not affected. There were no
      changes in the expression or the activity of the respective inhibitors for MMP-9
      and MMP-2, and tissue inhibitor of metalloproteinases-1 and -2. CONCLUSIONS:
      These data demonstrate that femoral wire injury in the mouse is associated with a
      time-dependent increase in Galphaq expression. Inhibition of Galphaq alters cell
      proliferation and is associated with decreased MMP-9 expression and activity.

PMID- 22595018
TI  - Erythropoietin improves the efficiency of endothelial progenitor cell therapy
      after myocardial infarction in mice: effects on transplanted cell survival and
      autologous endothelial progenitor cell mobilization.
AB  - BACKGROUND: Endothelial progenitor cells (EPCs) participate in vascular repair
      and angiogenesis. Thus, EPC transplantation into ischemic myocardium might
      improve cardiac function; however, the vast majority of cells die within a short
      period. The present study was designed to investigate whether exogenous
      erythropoietin (EPO) delivery could improve the survival of transplanted EPCs and
      enhance the efficiency of EPC-based cell therapy. METHODS: Myocardial infarction
      was induced in wild-type mice by ligating the left anterior descending coronary
      artery. Enhanced green fluorescent protein-EPCs with or without EPO were
      transplanted into peri-infarct myocardium. Enhanced green fluorescent protein
      EPCs were detected 7 and 28 d after surgery. The amount of circulating EPCs was
      analyzed 3 and 28 d after surgery. The stromal cell-derived factor-1alpha and
      vascular endothelial growth factor concentrations, microvessel density,
      apoptosis, fibrosis in the peri-infarct myocardium, and cardiac function were
      compared among the groups. RESULTS: More enhanced green fluorescent protein-EPCs
      were found in the hearts treated with EPC + EPO than in those treated with EPC
      alone. The circulating EPC level was markedly elevated after EPC + EPO treatment
      compared with EPC application alone. Stromal cell-derived factor-1alpha and
      vascular endothelial growth factor were increased accordingly, along with
      increased microvessel density, decreased apoptosis, and reduced fibrosis in the
      peri-infarct myocardium. Left ventricular fractional shortening was greater and
      the interventricular septum was thicker after EPC + EPO treatment compared with
      EPC treatment alone. CONCLUSIONS: EPO improved the efficiency of EPC therapy in
      mice with myocardial infarction. This effect was associated with enhanced
      transplanted EPC survival and autologous EPC mobilization.

PMID- 22595019
TI  - Robust cognitive change.
AB  - Two major challenges facing researchers interested in cognitive change are that
      measures of change are often not very reliable, and they may reflect effects of
      prior test experience in addition to the factors of primary interest. One
      approach to dealing with these problems is to obtain multiple measures of change
      on parallel versions of the same tests in a measurement burst design. A total of
      783 adults performed three parallel versions of cognitive tests on two occasions
      separated by an average of 2.6 years. Performance increased substantially across
      the three sessions within each occasion, and for all but vocabulary ability these
      within-occasion improvements were considerably larger than the between-occasion
      changes. Reliabilities of the changes in composite scores were low, but averages
      of the three changes had larger, albeit still quite modest, reliabilities. In
      some cognitive abilities individual differences were evident in the relation of
      prior test experience and the magnitude of longitudinal change. Although multiple
      assessments are more time consuming than traditional measurement procedures, the
      resulting estimates of change are more robust than those from conventional
      methods, and also allow the influence of practice on change to be systematically
      investigated.

PMID- 22595020
TI  - The effect of ubiquinone in diabetic polyneuropathy: a randomized double-blind
      placebo-controlled study.
AB  - INTRODUCTION: Diabetic polyneuropathy aetiology is based on oxidative stress
      generation due to production of reactive oxygen species. Ubiquinone is reduced to
      ubiquinol and redistributed into lipoproteins, possibly to protect them from
      oxidation. AIMS: To evaluate the impact of oral ubiquinone in diabetic
      polyneuropathy, and the role of lipid peroxidation (LPO) and nerve growth factor
      (NGF-beta). METHODS: We conducted a double-blind, placebo-controlled clinical
      trial, patients were randomized to ubiquinone (400 mg) or placebo daily for 12
      weeks. Main outcomes were clinical scores, nerve conduction studies, LPO, NGF
      beta and safety. RESULTS: Twenty four patients on experimental group and twenty
      five on control group met the inclusion criteria (mean age 56 years, 22% male and
      78% female, mean evolution of type 2 diabetes mellitus 10.7 years). Significant
      improvement on experimental vs control group was found in neuropathy symptoms
      score (from 2.5 +/- 0.7 to 1 +/- 0.8, p<0.001), neuropathy impairment score (5.5
      +/- 4 to 3.1 +/- 2.6, p<0.001), sural sensory nerve amplitude (13.0 +/- 6.1 to
      15.8 +/- 5.1 MUV, p=0.049), peroneal motor nerve conduction velocity (39.7 +/-
      5.0 to 47.8 +/- 4.9 m/s, p=0.047), and ulnar motor nerve conduction velocity
      (48.8 +/- 6.8 to 54.5 +/- 6.1m/s, p=0.046). There was a significant reduction of
      LPO in subjects treated with ubiquinone vs placebo (16.7 +/- 8.6 and 23.2 +/-
      15.8 nmol/mL, respectively) with p<0.05, and NGF-beta did not change (control
      66.5 +/- 26.7 vs. experimental 66.8 +/- 28.4 pg/mL, p=0.856). No drug-related
      adverse reactions were reported. CONCLUSIONS: Twelve weeks treatment with
      ubiquinone improves clinical outcomes and nerve conduction parameters of diabetic
      polyneuropathy; furthermore, it reduces oxidative stress without significant
      adverse events.

PMID- 22595021
TI  - Lack of effect of chronic pre-treatment with the FAAH inhibitor URB597 on
      inflammatory pain behaviour: evidence for plastic changes in the endocannabinoid
      system.
AB  - BACKGROUND AND PURPOSE: Elevating levels of endocannabinoids with inhibitors of
      fatty acid amide hydrolase (FAAH) is a major focus of pain research, purported to
      be a safer approach devoid of cannabinoid receptor-mediated side effects. Here,
      we have determined the effects of sustained pharmacological inhibition of FAAH on
      inflammatory pain behaviour and if pharmacological inhibition of FAAH was as
      effective as genetic deletion of FAAH on pain behaviour. EXPERIMENTAL APPROACH:
      Effects of pre-treatment with a single dose, versus 4 day repeated dosing with
      the selective FAAH inhibitor, URB597 (i.p. 0.3 mg.kg-1), on carrageenan-induced
      inflammatory pain behaviour and spinal pro-inflammatory gene induction were
      determined in rats. Effects of pain induction and of the drug treatments on
      levels of arachidonoyl ethanolamide (AEA), palmitoyl ethanolamide (PEA) and
      oleolyl ethanolamide (OEA) in the spinal cord were determined. KEY RESULTS:
      Single, but not repeated, URB597 treatment significantly attenuated the
      development of inflammatory hyperalgesia (P < 0.001, vs. vehicle-treated
      animals). Neither mode of URB597 treatment altered levels of AEA, PEA and OEA in
      the hind paw, or carrageenan-induced paw oedema. Single URB597 treatment produced
      larger increases in AEA, PEA and OEA in the spinal cord, compared with those
      after repeated administration. Single and repeated URB597 treatment decreased
      levels of immunoreactive N-acylphosphatidylethanolamine phospholipase D (NAPE
      PLD) in the spinal cord and attenuated carrageenan-induced spinal pro
      inflammatory gene induction. CONCLUSION AND IMPLICATIONS: Changes in the
      endocannabinoid system may contribute to the loss of analgesic effects following
      repeated administration of low dose URB597 in this model of inflammatory pain.

PMID- 22595022
TI  - Preso regulation of dendritic outgrowth through PI(4,5)P2-dependent PDZ
      interaction with betaPix.
AB  - In neuronal development, dendritic outgrowth and arborization are important for
      the establishment of neural circuit formation. A previous study reported that PSD
      95-interacting regulator of spine morphogenesis (Preso) formed a complex with PAK
      interacting exchange factor-beta (betaPix) via PSD-95/Dlg/ZO-1 (PDZ) interaction.
      Here, we report that Preso and its binding protein, betaPix, are localized in
      dendritic growth cones. Knockdown and dominant-negative inhibition of Preso in
      cultured neurons markedly reduced the dendritic outgrowth but not branching, and
      led to a decrease in the intensity of betaPix and F-actin in neuronal dendritic
      tips. Moreover, phosphatidylinositol 4,5-bisphosphate (PIP(2) ) induced a
      conformational change in Preso toward the open PDZ domain and enhanced the
      interaction with betaPix. In addition, the Preso band 4.1 protein, ezrin, radixin
      and moesin (FERM) domain mutant is unable to interact with PIP(2) and it did not
      rescue the Preso-knockdown effect. These results indicate that PIP(2) is a key
      signalling molecule that regulates dendritic outgrowth through activation of
      small GTPase signalling via interaction between Preso and betaPix.

PMID- 22595023
TI  - Effect of leisure time physical activity on severe knee or hip osteoarthritis
      leading to total joint replacement: a population-based prospective cohort study.
AB  - BACKGROUND: Studies on leisure time physical activity as risk factor or
      protective factor for knee or hip osteoarthritis (OA) show divergent results.
      Longitudinal prospective studies are needed to clarify the association of
      physical activity with future OA. The aim was to explore in a prospective
      population-based cohort study the influence of leisure time physical activity on
      severe knee or hip OA, defined as knee or hip replacement due to OA. METHODS:
      Leisure time physical activity was reported by 28320 participants (mean age 58
      years (SD 7.6), 60% women) at baseline. An overall leisure time physical activity
      score, taking both duration and intensity of physical activities into account,
      was created. The most commonly reported activities were also used for analysis.
      The incidence of knee or hip replacement due to OA over 11 years was monitored by
      linkage with the Swedish hospital discharge register. Cox's proportional hazards
      model (crude and adjusted for potential confounding factors) was used to assess
      the incidence of total joint replacement, or osteotomy (knee), in separate
      analyses of leisure time physical activity. RESULTS: There was no significant
      overall association between leisure time physical activity and risk for knee or
      hip replacement due to OA over the 11-year observation time. For women only, the
      adjusted RR (95% CI) for hip replacement was 0.66 (0.48, 0.89) (fourth vs. first
      quartile), indicating a lower risk of hip replacement in those with the highest
      compared with the lowest physical activity. The most commonly reported activities
      were walking, bicycling, using stairs, and gardening. Walking was associated with
      a lower risk of hip replacement (adjusted RR 0.76 (95% CI 0.61, 0.94),
      specifically for women (adjusted RR 0.75 (95% CI 0.57, 0.98)). CONCLUSIONS: In
      this population-based study of middle-aged men and women, leisure time physical
      activity showed no consistent overall relationship with incidence of severe knee
      or hip OA, defined as joint replacement due to OA, over 11 years. For women,
      higher leisure time physical activity may have a protective role for the
      incidence of hip replacement. Walking may have a protective role for hip
      replacement, specifically for women.

PMID- 22595024
TI  - Relation between total tear IgE and severity of acute seasonal allergic
      conjunctivitis.
AB  - PURPOSE: Measurement of total tear immunoglobulin E (IgE) is useful for the
      diagnosis of allergic conjunctivitis, but it is still unknown whether measurement
      of total tear IgE is useful for assessment of the severity of allergic
      conjunctivitis. We evaluated the relation between the total IgE level in tears
      and objective signs of allergic conjunctivitis. METHODS: A prospective,
      nonrandomized, and cross-sectional study was conducted in 84 patients with
      allergic conjunctivitis (allergic group) and 80 age- and sex-matched healthy
      control subjects (control group). The total tear IgE score was obtained with the
      Allerwatch((r)) test (0, 1, and 2), and ten severity scores (0, 1, 2, 3) were
      determined for objective ocular findings of the palpebral and bulbar conjunctiva,
      as well as limbal and corneal lesions. RESULTS: The scores for total tear IgE and
      each of the objective ocular findings were higher in the allergic group than in
      the control group (all p < 0.01). The total tear IgE score was correlated with
      the severity of each clinical feature of allergic conjunctivitis (p < 0.01),
      except for corneal epithelial damage in the allergic group. Multivariate analysis
      revealed that the severity of giant papillae was the most important indicator of
      the total tear IgE score (odds ratio = 1.33, p < 0.00001). CONCLUSION: The total
      tear IgE score was correlated with the scores for objective signs of allergic
      conjunctivitis. This rapid test for total IgE in tear fluid is easy to perform
      and could be used to assess the severity of allergic conjunctivitis on an
      outpatient basis.

PMID- 22595025
TI  - A new rabbit model for the study of early brain injury after subarachnoid
      hemorrhage.
AB  - INTRODUCTION: Pathophysiological disturbances during subarachnoid hemorrhage
      (SAH) and within the first few days thereafter are responsible for significant
      brain damage. Early brain injury (EBI) after SAH has become the focus of current
      research activities. The purpose of the present study was to evaluate whether a
      novel rabbit SAH model provokes EBI by means of neuronal degeneration, brain
      tissue death, and apoptosis in cerebral vascular endothelial cells. MATERIALS AND
      METHODS: SAH was performed using an extra-intracranial blood shunt. Intracranial
      pressure (ICP), cerebral perfusion pressure (CPP), and bilateral regional
      cerebral blood flow (rCBF) were continuously measured. Apoptosis and
      neurodegeneration were detected 24h post-SAH in basilar artery endothelial cells,
      bilateral basal cortex, and hippocampus (CA1 and CA3) using terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Fluoro
      jade B (FJB), respectively. RESULTS: ICP increase caused a CPP decrease to almost
      zero (8+/-5mmHg) and decreases in left and right rCBF to 23+/-8% and 19+/-9% of
      their baseline values. TUNEL- and FJB-stained sections revealed significant
      apoptosis and neurodegeneration in both basal cortex and hippocampal regions
      compared to sham-operated animals. The apoptotic index in basilar artery
      endothelial cells was 74%+/-11%. CONCLUSIONS: The blood shunt rabbit SAH model
      elicits acute physiological dearrangements and provokes marked and consistent
      early damage to the hippocampus, basal cortex, and cerebral vasculature 24h
      thereafter. These findings make the model a valid tool for investigation of pre
      vasospasm pathophysiological mechanisms and novel treatment modalities.

PMID- 22595026
TI  - A simple reproducible and time saving method of semi-automatic dendrite spine
      density estimation compared to manual spine counting.
AB  - Estimation of spine number and spine density by manual counting under the
      assumption that all dendrite protrusions equal spines are often used in studies
      on neuroplasticity occurring during health, brain diseases, and different
      experimental paradigms. Manual spine counting is, however, time consuming and
      biased by inter-observer variation. We present accordingly a quick, reproducible
      and simple non-stereological semi-automatic spine density estimation method based
      on the irregularity of the dendrite surface. Using the freeware ImageJ program,
      microphotographs of Golgi impregnated hippocampal dendrites derived from a
      previously performed study on the impact of chronic restrained stress were
      binarized, skeletonized, and the skeleton endings assumed to represent spine
      positions were counted and the spine densities calculated. The results based on
      754 dendrite fragments were compared to manual spine counting of the same
      dendrite fragments using the Bland-Altman method. The results from both methods
      were correlated (r=0.79, p<0.0001), The semi-automatic counting method gave a
      statistically higher (approx. 4%) spine density number, but both counting methods
      showed similar significant differences between the groups in the CA1 area, and no
      differences between the groups in the CA3 area. In conclusion, the presented semi
      automatic spine density estimation method yields consistently a higher spine
      density number than manual counting resulting in similar significance between
      groups. The proposed method may therefore be a reproducible time saving and
      useful non-stereological approach to spine counting in neuroplasticity studies
      requiring analysis of hundreds of dendrites.

PMID- 22595027
TI  - Mitochondrial respiratory chain dysfunction: implications in neurodegeneration.
AB  - For decades mitochondria have been considered static round-shaped organelles in
      charge of energy production. In contrast, they are highly dynamic cellular
      components that undergo continuous cycles of fusion and fission influenced, for
      instance, by oxidative stress, cellular energy requirements, or the cell cycle
      state. New important functions beyond energy production have been attributed to
      mitochondria, such as the regulation of cell survival, because of their role in
      the modulation of apoptosis, autophagy, and aging. Primary mitochondrial diseases
      due to mutations in genes involved in these new mitochondrial functions and the
      implication of mitochondrial dysfunction in multifactorial human pathologies such
      as cancer, Alzheimer and Parkinson diseases, or diabetes has been demonstrated.
      Therefore, mitochondria are set at a central point of the equilibrium between
      health and disease, and a better understanding of mitochondrial functions will
      open new fields for exploring the roles of these mitochondrial pathways in human
      pathologies. This review dissects the relationships between activity and assembly
      defects of the mitochondrial respiratory chain, oxidative damage, and alterations
      in mitochondrial dynamics, with special focus on their implications for
      neurodegeneration.

PMID- 22595028
TI  - Impaired response inhibition in veterans with post-traumatic stress disorder and
      mild traumatic brain injury.
AB  - Combat veterans with post-traumatic stress disorder (PTSD) can show impairments
      in executive control and increases in impulsivity. The current study examined the
      effects of PTSD on motor response inhibition, a key cognitive control function. A
      Go/NoGo task was administered to veterans with a diagnosis of PTSD based on semi
      structured clinical interview using DSM-IV criteria (n = 40) and age-matched
      control veterans (n = 33). Participants also completed questionnaires to assess
      self-reported levels of PTSD and depressive symptoms. Performance measures from
      the patients (error rates and reaction times) were compared to those from
      controls. PTSD patients showed a significant deficit in response inhibition,
      committing more errors on NoGo trials than controls. Higher levels of PTSD and
      depressive symptoms were associated with higher error rates. Of the three symptom
      clusters, re-experiencing was the strongest predictor of performance. Because the
      co-morbidity of mild traumatic brain injury (mTBI) and PTSD was high in this
      population, secondary analyses compared veterans with PTSD+mTBI (n = 30) to
      veterans with PTSD only (n = 10). Although preliminary, results indicated the two
      patient groups did not differ on any measure (p > .88). Since cognitive
      impairments could hinder the effectiveness of standard PTSD therapies,
      incorporating treatments that strengthen executive functions might be considered
      in the future. (JINS, 2012, 18, 1-10).

PMID- 22595029
TI  - Expression of pair rule gene orthologs in the blastoderm of a myriapod: evidence
      for pair rule-like mechanisms?
AB  - BACKGROUND: A hallmark of Drosophila segmentation is the stepwise subdivision of
      the body into smaller and smaller units, and finally into the segments. This is
      achieved by the function of the well-understood segmentation gene cascade. The
      first molecular sign of a segmented body appears with the action of the pair rule
      genes, which are expressed as transversal stripes in alternating segments.
      Drosophila development, however, is derived, and in most other arthropods only
      the anterior body is patterned (almost) simultaneously from a pre-existing field
      of cells; posterior segments are added sequentially from a posterior segment
      addition zone. A long-standing question is to what extent segmentation mechanisms
      known from Drosophila may be conserved in short-germ arthropods. Despite the
      derived developmental modes, it appears more likely that conserved mechanisms can
      be found in anterior patterning. RESULTS: Expression analysis of pair rule gene
      orthologs in the blastoderm of the pill millipede Glomeris marginata (Myriapoda:
      Diplopoda) suggests that these genes are generally involved in segmenting the
      anterior embryo. We find that the Glomeris pairberry-1 ( pby-1) gene is expressed
      in a pair rule pattern that is also found in insects and a chelicerate, the mite
      Tetraynchus urticae. Other Glomeris pair rule gene orthologs are expressed in
      double segment wide domains in the blastoderm, which at subsequent stages split
      into two stripes in adjacent segments. CONCLUSIONS: The expression patterns of
      the millipede pair rule gene orthologs resemble pair rule patterning in
      Drosophila and other insects, and thus represent evidence for the presence of an
      ancestral pair rule-like mechanism in myriapods. We discuss the possibilities
      that blastoderm patterning may be conserved in long-germ and short-germ
      arthropods, and that a posterior double segmental mechanism may be present in
      short-germ arthropods.

PMID- 22595030
TI  - Anti-angiogenic effects of the tubulysin precursor pretubulysin and of simplified
      pretubulysin derivatives.
AB  - BACKGROUND AND PURPOSE: The use of tubulin-binding compounds, which act in part
      by inhibiting tumour angiogenesis, has become an integral strategy of tumour
      therapy. Recently, tubulysins were identified as a novel class of natural
      compounds of myxobacterial origin, which inhibit tubulin polymerization. As these
      compounds are structurally highly complex, the search for simplified precursors
      [e.g. pretubulysin (Prt)] and their derivatives is mandatory to overcome supply
      problems hampering clinical development. We tested the anti-angiogenic efficacy
      of Prt and seven of its derivatives in comparison to tubulysin A (TubA).
      EXPERIMENTAL APPROACH: The compounds were tested in cellular angiogenesis assays
      (proliferation, cytotoxicity, cell cycle, migration, chemotaxis, tube formation)
      and in vitro (tubulin polymerization). The efficacy of Prt was also tested in
      vivo in a murine subcutaneous tumour model induced with HUH7 cells; tumour size
      and vascularization were measured. KEY RESULTS: The anti-angiogenic potency of
      all the compounds tested ran parallel to their inhibition of tubulin
      polymerization in vitro. Prt showed nearly the same efficacy as TubA (EC(50) in
      low nanomolar range in all cellular assays). Some modifications in the Prt
      molecule caused only a moderate drop in potency, while others resulted in a
      dramatic loss of action, providing initial insight into structure-activity
      relations. In vivo, Prt completely prevented tumour growth and reduced vascular
      density to 30%. CONCLUSIONS AND IMPLICATIONS: Prt, a chemically accessible
      precursor of some tubulysins is a highly attractive anti-angiogenic compound both
      in vitro and in vivo. Even more simplified derivatives of this compound still
      retain high anti-angiogenic efficacy.

PMID- 22595031
TI  - All-cause mortality and pharmacological treatment intensity following a high risk
      screening program for diabetes. A 6.6 year follow-up of the ADDITION study,
      Denmark.
AB  - AIM: To study all-cause mortality and pharmacological treatment intensity in
      relation to baseline glucose metabolism and HbA1c following high risk screening
      for diabetes in primary care. METHODS: Persons aged 40-69 years (N=163,185)
      received mailed diabetes risk questionnaires. 20,916 persons without diabetes but
      with high risk of diabetes were stratified by glucose metabolism (normal glucose
      tolerance (NGT), dysglycemia (IFG or IGT) or diabetes) and by HbA1c at screening
      (<6%, 6.0-6.4% or >= 6.5%). Median follow-up was 6.6 years. Excess mortality was
      calculated by hazard ratio. RESULTS: HR for all-cause mortality increased with
      increasing levels of HbA1c at screening in people with NGT and dysglycemia. In
      people with screen detected diabetes the opposite relation was found. In people
      with diabetes redeemed prescription rates for lipid-, blood pressure- and glucose
      lowering drugs increased significantly following screening and prescription rates
      increased with increasing levels of HbA1c at screening. The same trend in
      redeemed prescriptions was seen for people with dysglycemia and NGT, but the
      absolute rates were significantly lower than those among people with screen
      detected diabetes. CONCLUSIONS: This study confirms HbA1c as an independent
      predictor of all-cause mortality in non-diabetic individuals. A likely
      explanation for the inverse relation found between all-cause mortality and HbA1c
      at screening among those with screen detected diabetes would be that intensive
      treatment near-normalizes mortality. The small group of people with NGT and HbA1c
      >= 6.5%, who had the highest all-cause mortality, may benefit from being labelled
      and treated as having diabetes although this group may have special
      characteristics not accounted for in this study.

PMID- 22595033
TI  - Dissociation of BOLD responses to reward prediction errors and reward receipt by
      a model comparison.
AB  - The representation of reward anticipation and reward prediction errors is the
      basis for reward-associated learning. The representation of whether or not a
      reward occurred (reward receipt) is important for decision making. Recent studies
      suggest that, while reward anticipation and reward prediction errors are encoded
      in the midbrain and the ventral striatum, reward receipts are encoded in the
      medial orbitofrontal cortex. In order to substantiate this functional
      specialization we analyzed data from an fMRI study in which 59 subjects completed
      two simple monetary reward paradigms. Because reward receipts and reward
      prediction errors were correlated, a statistical model comparison was applied
      separating the effects of the two. Reward prediction error fitted BOLD responses
      significantly better than reward receipt in the midbrain and the ventral
      striatum. Conversely, reward receipt fitted BOLD responses better in the
      orbitofrontal cortex. Activation related to reward anticipation was found in the
      orbitofrontal cortex. The results confirm a functional specialization of
      behaviorally important aspects of reward processing within the mesolimbic
      dopaminergic system.

PMID- 22595032
TI  - An economic evaluation of pregabalin versus usual care in the management of
      community-treated patients with refractory painful diabetic peripheral neuropathy
      in primary care settings.
AB  - OBJECTIVE: To estimate the cost-effectiveness of pregabalin versus usual care
      (UC) in the management of community-treated patients with refractory painful
      diabetic peripheral neuropathy (pDPN) in primary care settings (PCS) in Spain.
      METHODS: Data was extracted from a 12-week registry study assessing costs of
      neuropathic pain in Spain. Pregabalin-naive outpatients treated with UC or newly
      prescribed pregabalin were selected for inclusion in the cost-effectiveness
      analysis. Effectiveness was expressed as quality-adjusted life years (QALY) gain.
      Perspectives of the Spanish National Health System (NHS) and society (2006) were
      applied for cost calculations. Results were expressed as incremental cost
      effectiveness ratio (ICER). Bootstrapping techniques (10,000 re-samples) were
      used to obtain the probabilistic ICER and the cost-effectiveness acceptability
      curve. RESULTS: A total of 189 patients were included in the economic analysis.
      Compared with UC, pregabalin was associated with higher QALY gain in a period of
      12-weeks; 0.0406+/-0.0343 versus 0.0285+/-0.0350 (p=0.167). Overall total costs
      (?1368+/-1229 vs. ?1258+/-1474; p=0.587) and healthcare costs (?628+/-590 vs.
      ?469+/-420; p=0.134) were similar for both pregabalin and UC, respectively. ICERs
      for pregabalin varied from ?5302 (95% CI: dominant; ?144,105) for total costs to
      ?14,381 (dominant; ?115,648) for healthcare costs. Probabilistic sensitivity
      analyses showed that 79-84% of ICERs were below the threshold of ?30,000/QALY.
      CONCLUSION: This study suggests that pregabalin may be cost-effective in the
      management of community-treated refractory outpatients, with pDPN when compared
      with usual care in the primary care setting in Spain. These findings may help
      policy makers when making health decision in the management of diabetes in the
      community.

PMID- 22595034
TI  - Reliable structural interpretation of small-angle scattering data from bio
      molecules in solution--the importance of quality control and a standard reporting
      framework.
AB  - Small-angle scattering is becoming an increasingly popular tool for the study of
      bio-molecular structures in solution. The large number of publications with 3D
      structural models generated from small-angle solution scattering data has led to
      a growing consensus for the need to establish a standard reporting framework for
      their publication. The International Union of Crystallography recently
      established a set of guidelines for the necessary information required for the
      publication of such structural models. Here we describe the rationale for these
      guidelines and the importance of standardising the way in which small-angle
      scattering data from bio-molecules and associated structural interpretations are
      reported.

PMID- 22595035
TI  - Perceived discrimination and cognition in older African Americans.
AB  - Existing evidence suggests that psychosocial stress is associated with cognitive
      impairment in older adults. Perceived discrimination is a persistent stressor in
      African Americans that has been associated with several adverse mental and
      physical health outcomes. To our knowledge, the association of discrimination
      with cognition in older African Americans has not been examined. In a cohort of
      407 older African Americans without dementia (mean age = 72.9; SD = 6.4), we
      found that a higher level of perceived discrimination was related to poorer
      cognitive test performance, particularly episodic memory (estimate = -0.03; SE =
      .013; p < .05) and perceptual speed tests (estimate = -0.04; SE = .015; p < .05).
      The associations were unchanged after adjusting for demographics and vascular
      risk factors, but were attenuated after adjustment for depressive symptoms
      (Episodic memory estimate = -0.02; SE = 0.01; Perceptual speed estimate = -0.03;
      SE = 0.02; both p's = .06). The association between discrimination and several
      cognitive domains was modified by level of neuroticism. The results suggest that
      perceived discrimination may be associated with poorer cognitive function, but
      does not appear to be independent of depressive symptoms. (JINS, 2012, 18, 1-10).

PMID- 22595036
TI  - Characteristics of ACh-induced hyperpolarization and relaxation in rabbit jugular
      vein.
AB  - BACKGROUND AND PURPOSE: The roles played by endothelium-derived NO and
      prostacyclin and by endothelial cell hyperpolarization in ACh-induced relaxation
      have been well characterized in arteries. However, the mechanisms underlying ACh
      induced relaxation in veins remain to be fully clarified. EXPERIMENTAL APPROACH:
      ACh-induced smooth muscle cell (SMC) hyperpolarization and relaxation were
      measured in endothelium-intact and -denuded preparations of rabbit jugular vein.
      KEY RESULTS: In endothelium-intact preparations, ACh (<= 10-8 M) marginally
      increased the intracellular concentration of Ca2+ ([Ca2+](i)) in endothelial
      cells but did not alter the SMC membrane potential. However, ACh (10-10 -10-8 M)
      induced a concentration-dependent relaxation during the contraction induced by
      PGF(2alpha) and this relaxation was blocked by the NO synthase inhibitor N(omega)
      -nitro-l-arginine. ACh (10-8 -10-6 M) concentration-dependently increased
      endothelial [Ca2+](i) and induced SMC hyperpolarization and relaxation. These SMC
      responses were blocked in the combined presence of apamin [blocker of small
      conductance Ca2+-activated K+ (SK(Ca) , K(Ca) 2.3) channel], TRAM 34 [blocker of
      intermediate-conductance Ca2+ -activated K+ (IK(Ca) , K(Ca) 3.1) channel] and
      margatoxin [blocker of subfamily of voltage-gated K+ (K(V) ) channel, K(V) 1].
      CONCLUSIONS AND IMPLICATIONS: In rabbit jugular vein, NO plays a primary role in
      endothelium-dependent relaxation at very low concentrations of ACh (10-10 -10-8
      M). At higher concentrations, ACh (10-8 -3 * 10-6 M) induces SMC
      hyperpolarization through activation of endothelial IK(Ca) , K(V) 1 and
      (possibly) SK(Ca) channels and produces relaxation. These results imply that ACh
      regulates rabbit jugular vein tonus through activation of two endothelium
      dependent regulatory mechanisms.

PMID- 22595037
TI  - A model of partial reference frame transforms through pooling of gain-modulated
      responses.
AB  - In multimodal integration and sensorimotor transformation areas of the posterior
      parietal cortex (PPC), neural responses often appear encoded in spatial reference
      frames that are intermediate to the intrinsic sensory reference frames, for
      example, eye-centered for visual or head-centered for auditory stimulation. Many
      sensory responses in these areas are also modulated by direction of gaze. We
      demonstrate that certain types of mixed-frame responses can be generated by
      pooling gain-modulated responses--similar to how complex cells in the visual
      cortex are thought to pool the responses of simple cells. The proposed model
      simulates 2 types of mixed-frame responses observed in the PPC: in particular,
      sensory responses that shift differentially with gaze in horizontal and vertical
      dimensions and sensory responses that shift differentially for different start
      and end points along a single dimension of gaze. We distinguish these 2 types of
      mixed-frame responses from a third type in which sensory responses shift a
      partial yet approximately equal amount with each gaze shift. We argue that the
      empirical data on mixed-frame responses may be caused by multiple mechanisms, and
      we adapt existing reference-frame measures to distinguish between the different
      types. Finally, we discuss how mixed-frame responses may be revealing of the
      local organization of presynaptic responses.

PMID- 22595038
TI  - Cognitive effects of the acetylcholinesterase inhibitor, donepezil, in healthy,
      non-treatment seeking smokers: a pilot feasibility study.
AB  - BACKGROUND: There is a need to identify medications to aid in smoking cessation.
      Reducing withdrawal-related cognitive deficits represents a pharmacological
      target for new pharmacotherapies. Endogenous acetylcholine levels, which are
      modulated by acetylcholinesterase inhibitors (AChEIs), play an important role in
      smoking behavior and cognition. This pilot feasibility study tested whether an
      AChEI, donepezil, enhanced cognitive performance among healthy smokers. METHODS:
      Eighteen non-treatment seeking daily smokers (6 female) received either donepezil
      (5 mg q.d) or placebo (double-blind; 2:1 allocation ratio) for 4 weeks. Smoking
      rate, side effects, and neurocognitive measures of working memory (Letter-N-back)
      and sustained attention (Penn Continuous Performance Task) were assessed weekly.
      RESULTS: For the working memory task, there was a significant group*load*time
      interaction (p=0.03) indicating that the donepezil group demonstrated an increase
      in true positives from baseline to week 4 at the highest working memory load (3
      back). The placebo group showed no change in accuracy. For the sustained
      attention task, there was a marginal effect in the same direction for
      discriminability, or d', p=0.08. There were no significant effects on reaction
      time during either task. There was also a reduction in cigarettes per day in the
      placebo group, but not the donepezil group. CONCLUSIONS: AChEIs, such as
      donepezil, may have pro-cognitive effects among healthy smokers while they
      continue to smoke as usual. Given the association between cognitive deficits and
      relapse, AChEIs should be explored as potential therapeutics for smoking
      cessation.

PMID- 22595039
TI  - Behavioral effects of environmental enrichment during gestation in WKY and Wistar
      rats.
AB  - Effects of prenatal environmental enrichment (EE) were examined in Wistar Kyoto
      (WKY) "depressive- and anxious-like" rats and Wistar rats. During gestation, dams
      lived in standard cages or in EE cages. Their behavior during gestation and
      lactation was observed. On weaning day, they were tested in the forced swimming
      test, and corticosterone concentration was measured from their plasma. The
      offspring, reared in standard environment, were tested as juveniles or young
      adults in the elevated plus maze, open field and forced swimming tests.
      Corticosterone concentration in feces was analyzed. EE offspring showed more
      anxiety-like behaviors and less activity, compared to controls. Effects were more
      prominent in youth than in adulthood and in Wistar rats more than in WKY. EE
      lowered corticosterone concentration in young WKY rats' feces. EE induced changes
      in the dams' behavior during gestation and lactation. These changes in dams'
      behavior could be mediators of the effects on the offspring.

PMID- 22595040
TI  - Sensorimotor gating and memory deficits in an APP/PS1 double transgenic mouse
      model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder associated with
      cognitive deterioration and neuropsychiatric symptoms. Sensorimotor gating
      deficit has been identified in neuropsychiatric diseases. The aim of the present
      study was to evaluate the possible sensorimotor gating deficit and its
      correlation to memory impairment and cerebral beta-amyloid (Abeta) plaque
      deposits in an amyloid precursor protein (APP)/presenilin-1 (PS1) double
      transgenic mouse model of AD. The sensorimotor gating in 3-, 7- and-22-month-old
      non-transgenic and transgenic mice was evaluated in a prepulse inhibition (PPI)
      task. Results revealed that the PPI was lower in the 7- and 22-month-old
      transgenic mice compared with the age-matched control, while the response to
      startle pulse-alone in the transgenic and non-transgenic mice was comparable.
      Congo red staining showed that Abeta neuropathology of transgenic mice aggravated
      with age, and the 3-month-old transgenic mice started to have minimum brain Abeta
      plaques, corresponding to the early stage of AD phenotype. Furthermore, memory
      impairment in the 7-month-old transgenic mice was detected in a water maze test.
      These results suggest that the sensorimotor gating is impaired with the
      progressing of AD phenotype, and its deficit may be correlated to cerebral Abeta
      neuropathology and memory impairment in the APP/PS1 transgenic mouse model of AD.

PMID- 22595041
TI  - Ethics, patient rights and staff attitudes in Shanghai's psychiatric hospitals.
AB  - BACKGROUND: Adherence to ethical principles in clinical research and practice is
      becoming topical issue in China, where the prevalence of mental illness is
      rising, but treatment facilities remain underdeveloped. This paper reports on a
      study aiming to understand the ethical knowledge and attitudes of Chinese mental
      health professionals in relation to the process of diagnosis and treatment,
      informed consent, and privacy protection in clinical trials. METHODS: A self
      administered survey was completed by 1110 medical staff recruited from Shanghai's
      22 psychiatric hospitals. Simple random selection methods were used to identify
      target individuals from the computerized registry of staff. RESULTS: The final
      sample for analysis consisted 1094 medical staff (including 523 doctors, 542
      nurses, 8 pharmacologists and 21 other staff). The majority reported that their
      medical institutions had not established an Ethics Committee (87.8%) and agreed
      that Ethics Committees should be set up in their institutions (72.9%).
      Approximately half (52%) had not received systematic education in ethics, and
      almost all (89.1%) of the staff thought it was necessary. Nearly all participants
      (90.0%) knew the Shanghai Mental Health Regulations which was the first local
      regulations relating to mental health in China, but only 11% and 16.6%
      respectively knew of the Nuremberg Code and the Declaration of Helsinki. About
      half (51.8%) thought that the guardian should make the decision as to whether the
      patient participated in clinical trials or not. CONCLUSIONS: The study indicates
      that most psychiatric hospitals in Shanghai have no Medical Ethics Committee.
      More than half the medical staff had not received systematic education and
      training in medical ethics and they have insufficient knowledge of the ethical
      issues related to clinical practice and trials. Training in ethics is recommended
      for medical staff during their training and as ongoing professional development.

PMID- 22595043
TI  - Cisplatin and gemcitabine administered every two weeks in patients with locally
      advanced or metastatic urothelial carcinoma and impaired renal function.
AB  - BACKGROUND: Cisplatin-based combination chemotherapy is the mainstay of treatment
      for locally advanced or metastatic urothelial carcinoma. However, standard dose
      schedule of cisplatin cannot be used in patients with impaired renal function. We
      evaluated the safety and efficacy of gemcitabine and a split dose administration
      of cisplatin in patients with renal dysfunction. PATIENTS AND METHODS: Patients
      with locally advanced or metastatic urothelial carcinoma with creatinine
      clearance between 35 and 59 ml/min received gemcitabine 2500 mg/m(2) and
      cisplatin 35 mg/m(2) on day 1 and day 15 for an every 28 day schedule. RESULTS:
      Between March 2004 and November 2009, 38 patients were treated. Median creatinine
      clearance was 49 ml/min. Median number of cycles per patient was 3 (1-7). There
      were 15 partial responses (39%) and 12 patients had stable disease (31%). Median
      progression free survival and overall survival were 3.5 and 8.5 months (mo),
      respectively. Grade 3-4 haematological toxicities were: neutropenia 9%, anaemia
      6% and thrombocytopenia 16%. No patient developed renal toxicity. CONCLUSIONS:
      Biweekly gemcitabine and cisplatin is an active and feasible regimen in this
      subset of patients and could be an option for unfit patients. However, results
      seem not to be superior to those obtained with carboplatin based regimens in this
      population of patients.

PMID- 22595042
TI  - Increased oxidative stress in human fetal membranes overlying the cervix from
      term non-labouring and post labour deliveries.
AB  - Enzymatic breakdown of the collagen-rich extracellular matrix (ECM) that connects
      the amnion and chorion layers of the fetal membranes is one of the key events
      leading to rupture of membranes. Oxidant stress caused by increased formation of
      reactive oxygen species and/or reduced antioxidant capacity may predispose to
      membrane rupture, a major cause of preterm birth. The aim of this study was to
      determine the effect of human labour and supracervical (SC) apposition on
      antioxidant enzymes and 8-isoprostane (a marker of lipid peroxidation). To
      determine the effect of human labour on oxidative stress status, fetal membranes
      from the SC site (SCS) were collected from women at term Caesarean section (no
      labour), and from the site of membrane rupture (SOR) after spontaneous labour
      onset and delivery (post labour). To determine the effect of SC apposition on
      oxidative stress status, amnion was collected from the SCS and a distal site (DS)
      in women at term Caesarean section in the absence of labour. The release of 8
      isoprostane was significantly higher in amnion from the SCS compared to DS, and
      in fetal membranes from the SOR compared to the SCS. Glutathione peroxidase (GPx)
      and superoxide dismutase (SOD) activity were lower in amnion from the SC compared
      to DS. SOD gene expression and enzyme activity were lower in fetal membranes
      after labour. There was no difference in expression or activity in catalase, GPx
      and glutathione reductase (GSR) between no labour and post labour fetal
      membranes. In primary amnion cells, SOD supplementation significantly augmented
      IL-1beta induced MMP-9 expression and activity. In summary, non-labouring SC
      fetal membranes are characterised by reduced antioxidant enzyme activity when
      compared to distal membranes, and, as such, may be more susceptible to oxidative
      damage and thus membrane rupture.

PMID- 22595044
TI  - Therapy options and long-term results of sinonasal malignancies.
AB  - OBJECTIVES: Nasal and paranasal sinus malignancies are rare. The most common
      lesions are located in the nasal cavity and the maxillary sinus, although they
      also occur in the ethmoid, sphenoid and frontal sinuses. Treatment often combines
      surgery, radiotherapy and chemotherapy. Endoscopic surgical approaches are
      increasingly used in order to reduce the morbidity associated with standard open
      resection. The aim of our study was to analyse the long-term treatment results of
      sinonasal malignancies (SNM), with a special focus on surgical approaches.
      MATERIALS AND METHODS: A retrospective review of 123 patients treated in a
      tertiary referral centre from 1992 to 2008 was conducted, which included
      information on tumour stage, histology, treatment and follow-up. RESULTS: A
      variety of histological types were found with squamous cell carcinoma being the
      most frequent (n=38), followed by melanoma (n=24) and adenocarcinoma (n=21). Open
      surgery was performed in 55 patients, and endoscopic resection was performed in
      28 patients. Nineteen patients were treated with primary radiation therapy (RTX),
      four underwent primary chemotherapy (CTX), and 15 had primary chemoradiation
      (RCTX). Two patients died prior to therapy onset. A comparison of survival rates
      did not show a significant difference between the treatment groups. Patients that
      underwent endoscopic resection had significantly fewer postoperative
      complications. CONCLUSION: In carefully selected patients, endoscopic surgery of
      SNM showed a similar outcome as open surgery, but with a significantly lower
      complication rate.

PMID- 22595045
TI  - New rehabilitation protocol for oral sinus communications in BRONJ patients.

PMID- 22595046
TI  - Introduction: Therapeutic cancer vaccines.

PMID- 22595047
TI  - Sipuleucel-T for the treatment of advanced prostate cancer.
AB  - Sipuleucel-T is an autologous cellular immunotherapy designed to stimulate an
      immune response to prostate cancer that prolongs the overall survival of men with
      asymptomatic or minimally symptomatic metastatic castrate-resistant prostate
      cancer (CRPC). The clinical development program and key efficacy, safety, and
      immune response findings from the phase III studies are presented. The
      integration of sipuleucel-T into the treatment paradigm of advanced prostate
      cancer and future directions for research are discussed.

PMID- 22595048
TI  - Lymphoma vaccine therapy: next steps after a positive, controlled phase III
      clinical trial.
AB  - Many of the efforts toward developing vaccines against human malignancies have
      been frustrated by the lack of identification of a tumor-specific antigen that
      would allow tumor cells to be distinguished from normal cells. Idiotypic
      determinants of the surface immunoglobulin (Ig) associated with a given patient's
      B-cell lymphoma are unique to that tumor, and can thus serve as a tumor-specific
      marker. When conjugated to the immune carrier keyhole limpet hemocyanin (KLH),
      vaccination with an idiotype protein vaccine has been able to improve length of
      freedom from disease relapse in patients with follicular lymphoma (FL) in a
      minimal residual disease (MRD) state after induction therapy, as demonstrated in
      a recent randomized, controlled phase III trial. In addition to predictive
      biomarker discovery, using residual autologous tumor and blood samples from
      patients vaccinated on the phase III trial, we have now developed a next
      generation idiotype DNA vaccine with the goal of reducing vaccine production time
      while maintaining efficacy. A first-in-human study is planned to evaluate its use
      in patients with asymptomatic phase lymphoplasmacytic lymphoma.

PMID- 22595049
TI  - Vaccines for melanoma and renal cell carcinoma.
AB  - The inherent immunogenicity of melanoma and renal cell carcinoma (RCC) has made
      these tumors a focus of considerable research in vaccine development. Recent data
      from murine studies of immunosurveillance have highlighted the importance of both
      innate and adaptive immune responses in shaping a tumor's inherent susceptibility
      to immune surveillance and immunotherapy. Melanoma has been a useful model for
      the identification of tumor-associated antigens and a number of putative renal
      cell antigens have been described more recently. These antigens have been
      targeted using a variety of vaccine strategies, including protein- and peptide
      based vaccines, recombinant antigen-expressing vectors, and whole cell vaccine
      approaches. While evidence for clinical benefit has been disappointing to date,
      several current phase III clinical trials are in progress based on promising
      results from phase II studies. Accumulating data suggest that the tumor
      microenvironment and mechanisms of immunological escape by established tumors are
      significant barriers that must be overcome before vaccine therapy can be fully
      realized. This review will discuss the basis for vaccine development, describe
      some of the more promising vaccine strategies in development, and mention some of
      the tumor escape mechanisms that block effective anti-tumor immunity for melanoma
      and RCC.

PMID- 22595051
TI  - Dendritic/tumor fusion cells as cancer vaccines.
AB  - A promising cancer vaccine involves the fusion of dendritic cells (DCs) with
      tumor cells such that a broad array of tumor antigens are presented in the
      context of DC-mediated costimulation and stimulatory cytokines. In diverse animal
      models, vaccination with DC/tumor fusions results in protection from an otherwise
      lethal challenge of tumor cells and eradication of established disease. In phase
      I clinical studies, vaccination with DC/tumor fusions was well tolerated, and
      induced immunologic responses in the majority of patients and clinical responses
      in a subset. Vaccine efficacy may be blunted by the immunosuppressive milieu
      characteristic of patients with malignancy, including the increased presence of
      regulatory T cells, and inhibitory pathways such as the PD-1/PDL-1 pathway. A
      current focus of research interest lies in enhancing response to cancer vaccines,
      by combining vaccination with tumor cytoreduction, regulatory T-cell depletion,
      and blockade of critical inhibitory pathways.

PMID- 22595050
TI  - Whole cell vaccines--past progress and future strategies.
AB  - Cancer vaccines have shown success in curing tumors in preclinical models.
      Accumulating evidence also supports their ability to induce immune responses in
      patients. In many cases, these responses correlate with improved clinical
      outcomes. However, cancer vaccines have not yet demonstrated their true potential
      in clinical trials. This is likely due to the difficulty in mounting a
      significant anti-tumor response in patients with advanced disease because of pre
      existing tolerance mechanisms that are actively turning off immune recognition in
      cancer patients. This review will examine the recent progress being made in the
      design and implementation of whole cell cancer vaccines, one vaccine approach
      that simultaneously targets multiple tumor antigens to activate the immune
      response. These vaccines have been shown to induce antigen-specific T-cell
      responses. Preclinical studies evaluating these vaccines given in sequence with
      other agents and cancer treatment modalities support the use of immunomodulating
      doses of chemotherapy and radiation, as well as immune-modulating pathway
      targeted monoclonal antibodies, to enhance the efficacy of cancer vaccines. Based
      on emerging preclinical data, clinical trials are currently exploring the use of
      combinatorial immune-based therapies for the treatment of cancer.

PMID- 22595052
TI  - Clinical evaluation of TRICOM vector therapeutic cancer vaccines.
AB  - We have developed an "off-the-shelf" vector-based vaccine platform containing
      transgenes for carcinoma-associated antigens and multiple costimulatory molecules
      (designated TRICOM). Two TRICOM platforms have been evaluated both preclinically
      and in clinical trials. PROSTVAC consists of rV, rF-PSA-TRICOM and is being used
      in prostate cancer therapy trials. PANVAC consists of rV, rF-CEA-MUC1-TRICOM; the
      expression of the two pan-carcinoma transgenes CEA and MUC-1 renders PANVAC
      vaccination applicable for therapeutic applications for a range of human
      carcinomas. Many new paradigms have emerged as a consequence of completed and
      ongoing TRICOM vaccine trials, including (1) clinical evidence of patient benefit
      may be delayed, because multiple vaccinations may be necessary to induce a
      sufficient anti-tumor immune response; (2) survival, and not strict adherence to
      RECIST criteria or time-to-progression, may be the most appropriate trial
      endpoint when TRICOM vaccines are used as monotherapy; (3) certain patient
      populations are more likely to benefit from vaccine therapy as compared to other
      therapeutics; and (4) TRICOM vaccines combined with standard-of-care
      therapeutics, either concomitantly or sequentially, are feasible because of the
      limited toxicity of vaccines.

PMID- 22595053
TI  - Novel recombinant alphaviral and adenoviral vectors for cancer immunotherapy.
AB  - Although cellular immunotherapy based on autolgous dendritic cells (DCs)
      targeting antigens expressed by metastatic cancer has demonstrated clinical
      efficacy, the logistical challenges in generating an individualized cell product
      create an imperative to develop alternatives to DC-based cancer vaccines.
      Particularly attractive alternatives include in situ delivery of antigen and
      activation signals to resident antigen-presenting cells (APCs), which can be
      achieved by novel fusion molecules targeting the mannose receptor and by
      recombinant viral vectors expressing the antigen of interest and capable of
      infecting DCs. A particular challenge in the use of viral vectors is the well
      appreciated clinical obstacles to their efficacy, specifically vector-specific
      neutralizing immune responses. Because heterologous prime and boost strategies
      have been demonstrated to be particularly potent, we developed two novel
      recombinant vectors based on alphaviral replicon particles and a next-generation
      adenovirus encoding an antigen commonly overexpressed in many human cancers,
      carcinoembryonic antigen (CEA). The rationale for developing these vectors, their
      unique characteristics, the preclinical studies and early clinical experience
      with each, and opportunities to enhance their effectiveness will be reviewed. The
      potential of each of these potent recombinant vectors to efficiently generate
      clinically active anti-tumor immune response alone, or in combination, will be
      discussed.

PMID- 22595054
TI  - Clinical development of Listeria monocytogenes-based immunotherapies.
AB  - Active immunotherapy targeting dendritic cells (DCs) has shown great promise in
      preclinical models and in human clinical trials for the treatment of malignant
      disease. Sipuleucel-T (Provenge, Dendreon, Seattle, WA), which consists of
      antigen-loaded dendritic cells (DCs), recently became the first targeted
      therapeutic cancer vaccine to be approved by the US Food and Drug Administration
      (FDA). However, ex vivo therapies such as Provenge have practical limitations and
      elicit an immune response with limited scope. By contrast, live-attenuated
      Listeria monocytogenes (Lm) naturally targets DCs in vivo and stimulates both
      innate and adaptive cellular immunity. Lm-based vaccines engineered to express
      cancer antigens have demonstrated striking efficacy in several animal models and
      have resulted in encouraging anecdotal survival benefit in early human clinical
      trials. Two different Lm-based vaccine platforms have advanced into phase II
      clinical trials in cervical and pancreatic cancer. Future Lm-based clinical
      vaccine candidates are expected to feature polyvalent antigen expression and to
      be used in combination with other immunotherapies or conventional therapies such
      as radiotherapy and chemotherapy to augment efficacy.

PMID- 22595056
TI  - The potential beneficial effects of drugs on the immune response to vaccination.
AB  - Many immunotherapeutic agents in phase II cancer studies have given optimistic
      results, which were not confirmed in larger randomized studies. Here we explore
      the evidence that, contrary to previous opinion, many chemotherapeutic agents and
      other classes of drugs may enhance the response to therapeutic vaccines by
      reducing inflammation and/or by inhibiting regulatory T lymphocytes or myeloid
      derived suppressor cells. In addition, some of these agents, such as the
      immunomodulatory drugs, may produce marked costimulatory activities as in the
      case of lenalidomide, which also has marked anti-inflammatory properties. With
      the first approval for a vaccine-based therapy for prostate cancer, we propose
      that many more vaccines will be able to achieve approval, especially when
      combined with the optimal chemotherapy and/or immunomodulatory drug schedule.

PMID- 22595055
TI  - The tipping point for combination therapy: cancer vaccines with radiation,
      chemotherapy, or targeted small molecule inhibitors.
AB  - Therapeutic cancer vaccines are a unique treatment modality in that they initiate
      a dynamic process of activating the host immune system, which can then be
      exploited by concurrent or subsequent therapies. The addition of immunotherapy to
      standard-of-care cancer therapies has shown evidence of efficacy in preclinical
      models and in the clinical setting. This review examines the preclinical and
      clinical interactions between vaccine-mediated tumor-specific immune responses
      and local radiation, systemic chemotherapy, or select small molecule inhibitors,
      as well as the potential synergy between these modalities.

PMID- 22595057
TI  - Strategies to use immune modulators in therapeutic vaccines against cancer.
AB  - Cancers so much resemble self that they prove difficult for the immune system to
      eliminate, and those that have already escaped natural immunosurveillance have
      gotten past the natural immune barriers to malignancy. A successful therapeutic
      cancer vaccine must overcome these escape mechanisms. Our laboratory has focused
      on a multistep "push-pull" approach in which we combine strategies to overcome
      each of the mechanisms of escape. If tumor epitopes are insufficiently
      immunogenic, we increase their immunogenicity by epitope enhancement, improving
      their binding affinity to major histocompatibility complex (MHC) molecules. If
      the anti-tumor response is too weak or of the wrong phenotype, we use cytokines,
      costimulatory molecules, Toll-like receptor ligands, and other molecular
      adjuvants to increase not only the quantity of the response but also its quality,
      to push the response in the right direction. Finally, the tumor invokes multiple
      immunosuppressive mechanisms to defend itself, so we need to overcome those as
      well, including blocking or depleting regulatory cells or inhibiting regulatory
      molecules, to pull the response by removing the brakes. Some of these strategies
      individually have now been translated into human clinical trials in cancer
      patients. Combinations of these in a push-pull approach are promising for the
      successful immunotherapy of cancer.

PMID- 22595059
TI  - Mucinous colloid carcinoma of the colon metastatic to the breast.

PMID- 22595058
TI  - Cancer vaccines targeting the epithelial-mesenchymal transition: tissue
      distribution of brachyury and other drivers of the mesenchymal-like phenotype of
      carcinomas.
AB  - The epithelial-mesenchymal transition (EMT) is thought to be a critical step
      along the metastasis of carcinomas. In addition to gaining motility and
      invasiveness, tumor cells that undergo EMT also acquire increased resistance to
      many traditional cancer treatment modalities, including chemotherapy and
      radiation. As such, EMT has become an attractive, potentially targetable process
      for therapeutic interventions against tumor metastasis. The process of EMT is
      driven by a group of transcription factors designated as EMT transcription
      factors, such as Snail, Slug, Twist, and the recently identified T-box family
      member, Brachyury. In an attempt to determine which of these drivers of EMT is
      more amenable to targeted therapies and, in particular, T-cell-mediated
      immunotherapeutic approaches, we have examined their relative expression levels
      in a range of human and murine normal tissues, cancer cell lines, and human tumor
      biopsies. Our results demonstrated that Brachyury is a molecule with a highly
      restricted human tumor expression pattern. We also demonstrated that Brachyury is
      immunogenic and that Brachyury-specific CD8(+) T cells expanded in vitro are able
      to lyse Brachyury-positive tumor cells. We thus propose Brachyury as an
      attractive target for vaccination strategies designed to specifically target
      tumor cells undergoing EMT.

PMID- 22595060
TI  - Temporal trends in incidence of kidney stones among children: a 25-year
      population based study.
AB  - PURPOSE: We conducted a population based pediatric study to determine the
      incidence of symptomatic kidney stones during a 25-year period and to identify
      factors related to variation in stone incidence during this period. MATERIALS AND
      METHODS: The Rochester Epidemiology Project was used to identify all patients
      younger than 18 years who were diagnosed with kidney stones in Olmsted County,
      Minnesota from 1984 to 2008. Medical records were reviewed to validate first time
      symptomatic stone formers with identification of age appropriate symptoms plus
      stone confirmation by imaging or passage. The incidence of symptomatic stones by
      age, gender and study period was compared. Clinical characteristics of incident
      stone formers were described. RESULTS: A total of 207 children received a
      diagnostic code for kidney stones, of whom 84 (41%) were validated as incident
      stone formers. The incidence rate increased 4% per calendar year (p = 0.01)
      throughout the 25-year period. This finding was due to a 6% yearly increased
      incidence in children 12 to 17 years old (p = 0.02 for age * calendar year
      interaction) with an increase from 13 per 100,000 person-years between 1984 and
      1990 to 36 per 100,000 person-years between 2003 and 2008. Computerized
      tomography identified the stone in 6% of adolescent stone formers (1 of 18) from
      1984 to 1996 vs 76% (34 of 45) from 1997 to 2008. The incidence of spontaneous
      stone passage in adolescents did not increase significantly between these 2
      periods (16 vs 18 per 100,000 person-years, p = 0.30). CONCLUSIONS: The incidence
      of kidney stones increased dramatically among adolescents in the general
      population during a 25-year period. The exact cause of this finding remains to be
      determined.

PMID- 22595061
TI  - Editorial comment.

PMID- 22595062
TI  - Histology proved malpositioning of dextranomer/hyaluronic acid in submucosal
      ureter in patients after failed endoscopic treatment of vesicoureteral reflux.
AB  - PURPOSE: We histologically investigated the cause of failed endoscopic treatment
      of vesicoureteral reflux with dextranomer/hyaluronic acid injections in children.
      MATERIALS AND METHODS: A total of 192 children underwent dextranomer/hyaluronic
      acid injection at our institution between January 2008 and September 2010. The
      study population consisted of 13 children (22 ureters) with vesicoureteral reflux
      who underwent ureteroneocystostomy following failed endoscopic injections (1 to
      2) of dextranomer/hyaluronic acid. In all cases the dextranomer/hyaluronic acid
      was implanted in the mucosa of the mid to distal ureteral tunnel following
      hydrodistention of the ureter. The medical records were reviewed, and specimens
      of the archived distal ureters removed during surgery were examined
      histologically. RESULTS: Mean patient age was 4.1 years. Mean dose of
      dextranomer/hyaluronic acid was 0.9 ml (both treatments) and mean lag between
      treatments was 13.4 months. Indications for open surgery were recurrent urinary
      tract infections and/or residual or aggravated reflux grade IV or higher.
      Histological study revealed that the dextranomer/hyaluronic acid was
      malpositioned in 21 of 22 ureters, residing in the muscle fibers in 2, adventitia
      in 14 and periureteral space in 5. CONCLUSIONS: This is the first known study to
      provide a histologically proved cause of failure of endoscopic treatment of
      vesicoureteral reflux with dextranomer/hyaluronic acid injections in children.
      Malpositioning of the material outside the submucosal ureter was identified in a
      high percentage of cases. Larger studies are needed to corroborate these
      findings.

PMID- 22595063
TI  - The effects of oxybutynin on urinary symptoms in children with Williams-Beuren
      syndrome.
AB  - PURPOSE: Williams-Beuren syndrome is a genomic disorder caused by a hemizygous
      contiguous gene deletion on chromosome 7q11.23. Lower urinary tract symptoms are
      common in children with Williams-Beuren syndrome. However, there are few data on
      the management of voiding symptoms in this population. We report our experience
      using oxybutynin to treat urinary symptoms in children with Williams-Beuren
      syndrome. MATERIALS AND METHODS: We prospectively analyzed 42 patients with
      Williams-Beuren syndrome and significant lower urinary tract symptoms due to
      detrusor overactivity diagnosed on urodynamics in a 12-week, open-label study.
      Urological assessment included symptomatic evaluation, the impact of lower
      urinary tract symptoms on quality of life, frequency-volume chart, urodynamics
      and urinary tract sonography. After 12 weeks of treatment with 0.6 mg/kg
      oxybutynin per day given in 3 daily doses, patients were assessed for treatment
      efficacy and side effects. RESULTS: A total of 17 girls and 19 boys completed
      medical therapy and were assessed at 12 weeks. Mean +/- SD patient age was 9.2 +/
      4.3 years (range 3 to 18). The most common urinary complaint was urgency, which
      occurred in 31 patients (86.1%), followed by urge incontinence, which was seen in
      29 (80.5%). Compared to baseline, urinary symptoms were substantially improved.
      The negative impact of storage symptoms on quality of life was significantly
      decreased from a mean +/- SD of 3.3 +/- 1.7 to 0.5 +/- 0.9 (p <0.001). Mean +/-
      SD maximum urinary flow improved from 14.2 +/- 15.0 to 20.5 +/- 6.4 ml per second
      (p <0.001). CONCLUSIONS: A total of 12 weeks of therapy with 0.6 mg/kg oxybutynin
      daily resulted in improvement of lower urinary tract symptoms, quality of life
      and maximum flow rate in most patients with Williams-Beuren syndrome.

PMID- 22595064
TI  - Intractable hemorrhagic cystitis after hematopoietic stem cell tranplantation--is
      there a role for early urinary diversion in children?
AB  - PURPOSE: Severe hemorrhagic cystitis is a major complication in the pediatric
      population undergoing hematopoietic stem cell transplantation. Percutaneous
      nephrostomy tube drainage as a treatment for severe hemorrhagic cystitis has
      rarely been investigated. We examined children undergoing hematopoietic stem cell
      transplantation for risk factors associated with severe hemorrhagic cystitis, as
      well as our experience with percutaneous nephrostomy tube placement as an
      adjunctive management strategy. MATERIALS AND METHODS: Using prospectively
      collected data from the Blood and Marrow Transplant Database at the University of
      Minnesota, we reviewed 40 pediatric patients with severe hemorrhagic cystitis
      from 1996 to 2010. Specific treatment for each patient was administered at the
      discretion of the attending physician and generally included bladder irrigation
      before bladder fulguration or percutaneous nephrostomy tube placement. A
      percutaneous nephrostomy tube was placed in 11 patients due to the intractable
      nature of the hemorrhagic cystitis. RESULTS: Of the 11 patients who underwent
      percutaneous nephrostomy tube drainage 5 (45%) had improvement of the hemorrhagic
      cystitis within 30 days and the same number had long-term resolution. Among the
      patients with long-term resolution hemorrhagic cystitis resolved an average of
      12.4 days after percutaneous nephrostomy tube placement, and the tubes were
      removed an average of 8.8 weeks after placement. Through September 2011 mortality
      among patients with percutaneous nephrostomy tubes was 55% (6 of 11 patients),
      which was identical to the overall mortality in the severe hemorrhagic cystitis
      group (22 of 40). No death could be directly attributed to hemorrhagic cystitis
      or percutaneous nephrostomy tube placement. CONCLUSIONS: Placement of
      percutaneous nephrostomy tubes for treatment of severe hemorrhagic cystitis
      results in long-term improvement in intractable hemorrhagic cystitis, and is a
      safe and viable option for the majority of patients.

PMID- 22595065
TI  - Relationship among bacterial virulence, bladder dysfunction, vesicoureteral
      reflux and patterns of urinary tract infection in children.
AB  - PURPOSE: We hypothesized that virulence levels of Escherichia coli isolates
      causing pediatric urinary tract infections differ according to severity of
      infection and also among various uropathies known to contribute to pediatric
      urinary tract infections. We evaluated these relationships using in vitro
      cytokine interleukin-6 elicitation. MATERIALS AND METHODS: E. coli isolates were
      cultured from children presenting with urinary tract infections. In vitro
      cytokine (interleukin-6) elicitation was quantified for each isolate and the
      bacteria were grouped according to type of infection and underlying uropathy
      (neurogenic bladder, nonneurogenic bowel and bladder dysfunction, primary
      vesicoureteral reflux, no underlying etiology). RESULTS: A total of 40 E. coli
      isolates were collected from children with a mean age of 61.5 months (range 1 to
      204). Mean level of in vitro cytokine elicitation from febrile urinary tract
      infection producing E. coli was significantly lower than for nonfebrile strains
      (p = 0.01). The interleukin-6 response to E. coli in the neurogenic bladder group
      was also significantly higher than in the vesicoureteral reflux (p = 0.01) and no
      underlying etiology groups (p = 0.02). CONCLUSIONS: In vitro interleukin-6
      elicitation, an established marker to determine bacterial virulence, correlates
      inversely with clinical urinary tract infection severity. Less virulent, high
      cytokine producing E. coli were more likely to cause cystitis and were more
      commonly found in patients with neurogenic bladder and nonneurogenic bowel and
      bladder dysfunction, whereas higher virulence isolates were more likely to
      produce febrile urinary tract infections and to affect children with primary
      vesicoureteral reflux and no underlying etiology. These findings suggest that
      bacteria of different virulence levels may be responsible for differences in
      severity of pediatric urinary tract infections and may vary among different
      underlying uropathies.

PMID- 22595066
TI  - Revealing mental health status in Iran's capital: putting equity and efficiency
      together.
AB  - Information about urban health is often based on averages, while to better
      understand health status in urban areas, inequality should also be included. In
      this paper, we applied an achievement index approach in order to surmount this
      defect and to examine mental health status in Iran's capital, Tehran. The data we
      required for this study were taken from the Urban Health Equity Assessment and
      Response Tool (Urban HEART) survey which was conducted in Tehran in 2007,
      covering people aged 15 and above. The concentration index, which is a commonly
      used measure of socioeconomic inequalities in health, was extended to enable the
      combination of inequality and averages and the formation of a mental health
      achievement index. Values from the standard concentration indices showed that
      mental disorders are concentrated disproportionately among the poor in Tehran. An
      extension of the standard concentration indices revealed that, in most of
      Tehran's districts, the mental health of populations in the poorest quintile is
      much worse than that of other groups. In addition, when we computed the
      achievement index and ranked districts according to this index, the ranking was
      different from the ranking by averages. These findings imply that mental health
      varies significantly across the economic groups of the population in Tehran and
      that efficiency-oriented strategies which target average level of mental health
      alone are not sufficient to improve mental health of all people especially mental
      health of the poor. Equity-oriented strategies which target the mental health
      inequalities should be considered as well.

PMID- 22595067
TI  - Measuring the payback of research activities: a feasible ex-post evaluation
      methodology in epidemiology and public health.
AB  - Most ex-post evaluations of research funding programs are based on bibliometric
      methods and, although this approach has been widely used, it only examines one
      facet of the project's impact, that is, scientific productivity. More
      comprehensive models of payback assessment of research activities are designed
      for large-scale projects with extensive funding. The purpose of this study was to
      design and implement a methodology for the ex-post evaluation of small-scale
      projects that would take into account both the fulfillment of projects' stated
      objectives as well as other wider benefits to society as payback measures. We
      used a two-phase ex-post approach to appraise impact for 173 small-scale projects
      funded in 2007 and 2008 by a Spanish network center for research in epidemiology
      and public health. In the internal phase we used a questionnaire to query the
      principal investigator (PI) on the outcomes as well as actual and potential
      impact of each project; in the external phase we sent a second questionnaire to
      external reviewers with the aim of assessing (by peer-review) the performance of
      each individual project. Overall, 43% of the projects were rated as having
      completed their objectives "totally", and 40% "considerably". The research
      activities funded were reported by PIs as socially beneficial their greatest
      impact being on research capacity (50% of payback to society) and on knowledge
      translation (above 11%). The method proposed showed a good discriminating ability
      that makes it possible to measure, reliably, the extent to which a project's
      objectives were met as well as the degree to which the project contributed to
      enhance the group's scientific performance and of its social payback.

PMID- 22595068
TI  - Performance of female volunteer community health workers in Dhaka urban slums.
AB  - Volunteer community health workers (CHWs) are one approach to addressing the
      health workforce crisis in developing countries. BRAC, a large Bangladeshi NGO, a
      pioneer in this area, uses female volunteer CHWs as core workers in its health
      programs. After 25 years of implementing the CHW model in rural areas, BRAC has
      begun using female CHWs in urban slums through its community-based mother,
      newborn and child health interventions. However, the program experienced
      suboptimal performance among CHWs, with a high percentage of them remaining in
      their positions but becoming "inactive", not truly participating in daily
      community health activities. This suggests a need to better understand the
      relative importance of factors affecting their active participation and to
      recommend strategies for improving their participation. This mixed-method study
      included a descriptive correlational design to assess factors relating to level
      of activity of CHWs and focus group discussions to explore solutions to these
      problems. A sample of 542 current female CHWs from project areas participated in
      the survey. Financial incentives were the main factor linked to the activity of
      CHWs. CHWs who thought that running their families would be difficult without CHW
      income had more than three times greater odds to become active. In addition,
      social prestige and positive community feedback to the CHWs were important non
      financial factors associated with level of activity. In order to improve
      volunteer CHWs' performance, a combination of financial and non-financial
      incentives should be used.

PMID- 22595069
TI  - "From this place and of this place:" climate change, sense of place, and health
      in Nunatsiavut, Canada.
AB  - As climate change impacts are felt around the globe, people are increasingly
      exposed to changes in weather patterns, wildlife and vegetation, and water and
      food quality, access and availability in their local regions. These changes can
      impact human health and well-being in a variety of ways: increased risk of
      foodborne and waterborne diseases; increased frequency and distribution of vector
      borne disease; increased mortality and injury due to extreme weather events and
      heat waves; increased respiratory and cardiovascular disease due to changes in
      air quality and increased allergens in the air; and increased susceptibility to
      mental and emotional health challenges. While climate change is a global
      phenomenon, the impacts are experienced most acutely in place; as such, a sense
      of place, place-attachment, and place-based identities are important indicators
      for climate-related health and adaptation. Representing one of the first
      qualitative case studies to examine the connections among climate change, a
      changing sense of place, and health in an Inuit context, this research draws data
      from a multi-year community-driven case study situated in the Inuit community of
      Rigolet, Nunatsiavut, Canada. Data informing this paper were drawn from the
      narrative analysis of 72 in-depth interviews conducted from November 2009 to
      October 2010, as well as from the descriptive analysis of 112 questionnaires from
      a survey in October 2010 (95% response rate). The findings illustrated that
      climate change is negatively affecting feelings of place attachment by disrupting
      hunting, fishing, foraging, trapping, and traveling, and changing local
      landscapes-changes which subsequently impact physical, mental, and emotional
      health and well-being. These results also highlight the need to develop context
      specific climate-health planning and adaptation programs, and call for an
      understanding of place-attachment as a vital indicator of health and well-being
      and for climate change to be framed as an important determinant of health.

PMID- 22595070
TI  - Family income and childhood obesity in eight European cities: the mediating roles
      of neighborhood characteristics and physical activity.
AB  - Utilizing data from the Large Analysis and Review of European Housing and Health
      Status (LARES) research program conducted by the WHO in eight European cities
      (Forli, Vilnius, Ferreira do Alentejo, Bonn, Geneva, Angers, Bratislava,
      Budapest), we examined whether the well-documented inverse correlation between
      family income and children's BMI might be explained, in part, by access to open
      green space and ensuing physical activity. We found that household income was
      inversely related to BMI among 1184 children, ages 6-18 years of age. Utilizing
      structural equation modeling with statistical controls for age and gender, we
      found evidence for two indirect paths between household income and BMI. One
      indirect relationship operates successively through open green space and physical
      activity. The second path operates through physical activity alone. The child's
      height and weight as well as level of physical activity were reported by their
      mother. Open green space was assessed by trained observers' ratings of the area
      surrounding the child's home. Limitations of the study and implications for
      better understanding of the ecological context of obesity are discussed.

PMID- 22595071
TI  - Community-level socioeconomic status and parental smoking in Japan.
AB  - Community-level social environment has been considered to be associated with
      smoking behavior. However, no study has examined the association between
      community-level environmental factors and parental smoking behavior in families
      with young children. The aim of the present study was to examine the association
      between community-level socioeconomic status (SES) and parental smoking behavior.
      We used data from a cross-sectional study conducted from 2005 to 2006. We
      randomly selected 44 Japanese municipalities, 39 of which municipalities agreed
      to participate in this survey. The study subjects were participants in health
      check-ups for three-year-old children. Smoking status and individual demographic
      characteristics were obtained using self-administered questionnaires. Community
      level variables were obtained from national census data for 2005. The prevalence
      of employment in tertiary industries and of unemployment was used to measure
      community-level SES. Multilevel Poisson regression models were used to calculate
      prevalence ratios (PRs) for smoking. Of 4143 subjects, a total of 3301 parents in
      39 municipalities participated in our survey. Among the 2975 participants (71.8%)
      included in our analysis, 59.0% were smokers. There was no association between
      the job of the head of the household considered as an indicator of individual
      level SES and smoking. By contrast, when we examined the relationship between
      prevalence of employment in tertiary industries as community-level SES and
      smoking, parents living in low middle SES municipalities had a significantly
      higher prevalence ratio for smoking, compared to parents living in the highest
      SES municipalities. This result suggested that those with lower community-level
      SES tended to have a higher prevalence of parental smoking regardless of
      individual-level SES.

PMID- 22595072
TI  - High Caesarean section rate in rural China: is it related to health insurance
      (New Co-operative Medical Scheme)?
AB  - The epidemic of Caesarean section (CS) is worldwide, and it has been argued that
      it is mainly due to non-medical factors, including healthcare financing patterns.
      We investigated the use of CS in rural China and the related factors,
      particularly health insurance in the form of the New Co-operative Medical Scheme
      introduced in 2003. A cross-sectional survey of women who gave birth in 2008-2009
      was conducted in five rural counties in central and western China. Of the 5049
      new mothers, 73% were interviewed. The association between health insurance
      coverage and self-reported CS (divided into emergency and non-emergency CS) were
      examined by cross-tabulation and logistic regression, adjusting for maternal age,
      education, occupation, household income, previous abortions, parity and type of
      birth health facility. We found that 46% of all births (3550) were CSs, with 13%
      having an emergency and 33% a non-emergency CS. Women reported that half of the
      non-emergency CSs were recommended by a doctor and half were requested by
      themselves. In those counties with mid-range CS rates (28%-63%), health insurance
      coverage was associated with having CS, and particularly with having non
      emergency CS. In those counties with the highest (82%) and lowest (13%) rate,
      there was no statistically significant association. The findings suggest that
      health insurance coverage may have facilitated the overuse of CS. Further studies
      are needed to develop appropriate interventions to reduce non-medically indicated
      CS, focussing on payment mechanisms, healthcare provider practice patterns, and
      maternal requests.

PMID- 22595073
TI  - Idioms of distress, ethnopsychology, and the clinical encounter in Haiti's
      Central Plateau.
AB  - Haiti's 2010 earthquake mobilized mental health and psychosocial interventions
      from across the globe. However, failure to understand how psychological distress
      is communicated between lay persons and health workers in rural clinics, where
      most Haitians access care, has been a major limitation in providing mental health
      services. The goal of this study was to map idioms of distress onto Haitian
      ethnopsychologies in a way that promotes improved communication between lay
      persons and clinicians in rural Haiti. In Haiti's Central Plateau, an
      ethnographic study was conducted in May and June 2010, utilizing participant
      observation in rural clinics, 31 key informant interviews, 11 focus groups, and
      four case studies. Key informants included biomedical practitioners, traditional
      healers, community leaders, and municipal and religious figures. Deductive and
      inductive themes were coded using content analysis (inter-rater reliability >
      0.70). Forty-four terms for psychological distress were identified. Head (tet) or
      heart (ke) terms comprise 55% of all qualitative text segments coded for idioms
      of distress. Twenty-eight of 142 observed patient-clinician contacts involved
      persons presenting with tet terms, while 29 of the 142 contacts were
      presentations with ke terms. Thus, 40% of chief complaints were conveyed in
      either head or heart terms. Interpretations of these terms differed between lay
      and clinical groups. Lay respondents had broad and heterogeneous interpretations,
      whereas clinicians focused on biomedical concepts and excluded discussion of
      mental health concerns. This paper outlines preliminary evidence regarding the
      psychosocial dimensions of tet and ke-based idioms of distress and calls for
      further exploration. Holistic approaches to mental healthcare in Haiti's Central
      Plateau should incorporate local ethnopsychological frameworks alongside
      biomedical models of healthcare.

PMID- 22595074
TI  - Community based mangrove management: a review on status and sustainability.
AB  - Community Based Mangrove Management (CBMM) has been advocated by both academia
      and governing agencies as a viable alternative for sustainably managing the
      ecologically important mangrove forests which are disappearing rapidly worldwide.
      Drawing insights from diverse sustainability issues, capabilities and
      performances of worldwide CBMM initiatives were examined in this paper. Higher
      numbers of CBMM initiatives were reported from South Asia and lesser from South
      America and Africa. Identification of the causes of degradation at a site and use
      specific zonal replantations with respect to species associations were identified
      as major criteria of ecological sustainability. Regarding economic
      sustainability, transformation of potential uses of mangroves known by local
      communities into actual ones was found to be necessary. Proper disbursement of
      accrued benefits among community members irrespective of their socio-cultural
      status is also a major concern. Restructuring of CBMM institutions by ensuring
      participation of subsistence based users in decision-making and resource sharing
      have been identified as a prime determinant of institutional sustainability.
      However, limited number of studies on socio-political and institutional aspects
      as well as impacts of globalization induced socio-cultural transformations of
      communities on CBMM had been actually found. More focused researches on these
      aspects had been recommended for better community management of these highly
      stressed forests.

PMID- 22595075
TI  - Degradation of formaldehyde by advanced oxidation processes.
AB  - The degradation of formaldehyde in an aqueous solution (400 mg L(-1)) was studied
      using photolysis, peroxidation and advanced oxidation processes (UV/H(2)O(2),
      Fenton and photo-Fenton). Photolysis was the only process tested that did not
      reduce formaldehyde concentration; however, only advanced oxidation processes
      (AOPs) significantly decreased dissolved organic carbon (DOC). UV/H(2)O(2) and
      photo-Fenton AOPs were used to degrade formaldehyde at the highest concentrations
      (1200-12,000 mg L(-1)); the processes were able to reduce CH(2)O by 98% and DOC
      by 65%. Peroxidation with ultraviolet light (UV/H(2)O(2)) improved the efficiency
      of treatment of effluent from an anatomy laboratory. The effluent's CH(2)O
      content was reduced by 91%, DOC by 48%, COD by 46% and BOD by 53% in 420 min of
      testing.

PMID- 22595076
TI  - Environmental Impact Assessment--methodology with special emphasis on European
      pork production.
AB  - One of the most discussed topics worldwide is climate change, upon which
      livestock production is known to have a great environmental impact. There are
      different methods to measure these environmental impacts, some of which are
      mentioned in this review. It especially focuses on the method of Life Cycle
      Assessment (LCA), because it is widely used, of high relevance and good quality.
      This review highlights a sample of the few published European LCA studies on pork
      production. These assessments result in an average global warming potential of
      3.6 kg CO(2)- eq per kg pork, ranging from 2.6 to 6.3 kg CO(2)- eq per kg pork.
      Additionally, it illustrates the main limitations of the methodology itself (e.g.
      data intensiveness, different allocation techniques) and its application in pork
      production (e.g. limited data availability, use of multiple functional units,
      varying system boundaries). The missing comparability of various studies arising
      from a vague standard still represents the main problem in LCA. Therefore, a new
      standardisation and the development of a more exhaustive database would generate
      a future trend.

PMID- 22595077
TI  - Impact of percentile computation method on PM 24-h air quality standard.
AB  - In 1997, the US Environmental Protection Agency (US EPA) introduced a percentile
      form of the National Ambient Air Quality Standard (NAAQS) for particulate matter
      (PM). Studies had shown that a specified percentile in the frequency distribution
      of measured values of PM increased the probability of detecting non-attainment
      areas (power) and decreased the likelihood of misclassification of attainment
      areas as being non-attainment (type 2 error). However, this new NAAQS used a
      percentile form that was different from a standard percentile in a distribution.
      Instead of taking the percentile of the distribution of the required 3 years of
      measurements, the PM(2.5) values for the selected percentile for each year were
      determined and the average of these 3 values was used as the NAAQS indicator
      value. However, no studies have been made of this average of the 3 years method
      and compared to a standard percentile in the multiyear data. The relationships
      between the values obtained using these two approaches have been explored. PM
      data measured at selected US EPA Aerometric Information Retrieval System (AIRS)
      website from January 2004 to December 2008 at 20 sites in 20 different states in
      United States were utilized. PM samples were collected for 24-h periods from
      midnight to midnight every third day for PM(2.5) and every sixth day for PM(10).
      At some sites, continuous measurements of PM(2.5) were made and averaged to
      provide 24-hr values. Using these data, the NAAQS percentile values were compared
      with the actual 98th percentile values of the three years of data. Regression and
      t-test analyses were used to compare these two methods and found high correlation
      coefficients and no significant difference in most cases. Overall, the two
      methods showed substantial agreement such that either of the two approaches could
      serve as the statistical form of the 24-h standard. In exploring the PM(10)
      standard, an arbitrarily chosen standard value of 85 MUg/m(3) was used to explore
      the development of more stable implementation programs and provide better
      protection to public health against short term exposures.

PMID- 22595078
TI  - The role of discretion in recreation decision-making by resource professionals in
      the USDA Forest Service.
AB  - This paper explores opportunities for administrative discretion in decision
      making for natural resource management. We carried out an exploratory study in
      the USDA Forest Service to understand factors affecting administrative actions
      related to recreation use in riparian areas. We conducted semi-structured
      interviews with 27 resource professionals from a national forest in the northwest
      region of the United States. Questions focused on professional judgments about
      recreation in riparian areas, administrative actions related to management of
      these activities, and the potential for personal values to influence decisions.
      We analyzed the transcribed interviews using Atlas.ti, coding the data for
      salient themes. In this paper, we discuss perceptions of resource professionals
      about the potential for personal values to influence administrative actions and
      decisions. We highlight four distinct realms in the planning process where
      expanded discretionary capacity exists and values may emerge. Finally, we suggest
      ways to reduce the potential influence of value-based judgments in decision
      making.

PMID- 22595079
TI  - Extraction of phenanthrene and fluoranthene from contaminated sand using palm
      kernel and soybean oils.
AB  - Experimental extraction tests are conducted to investigate feasibility of
      saturated palm kernel oil (PKO) and unsaturated soybean oil (SO) to extract
      polycyclic aromatic hydrocarbons (PAHs) from contaminated sand. The extraction
      rates and efficiencies for lowly contaminated (LC) and highly contaminated (HC)
      sands at temperatures of 30  degrees C and 70  degrees C are evaluated using
      empirical first order kinetic dissolution models. In LC sand, the extraction is
      dominated by the diffusion of PAHs adsorbed onto particle surfaces and the direct
      dissolution of PAH phase. In HC sand, a rapid diffusion of PAHs adsorbed onto
      particle surfaces and a direct dissolution of PAH phase occur followed by a
      slower diffusion of PAHs entrapped within the pores and micropores. Larger
      diffusion resistance during HC sand extractions results in an average 10.8%
      reduction in extraction efficiencies compared to LC sand. Increased temperature
      generally increases the mass transfer rates and extraction efficiencies.
      Additionally, the physicochemical properties of both oils and PAHs also determine
      the extent of PAH extraction into oil.

PMID- 22595080
TI  - Identification of dimorphism-involved genes of Yarrowia lipolytica by means of
      microarray analysis.
AB  - Fungal dimorphism is the capacity of certain species of fungi to grow in the form
      of budding yeasts or mycelium depending on the environmental conditions. This
      characteristic is a complex phenomenon that involves modifications of the
      molecular machinery in response to different environmental signals. Through the
      use of microarrays, in this work we identified genes involved in the early stages
      of the yeast-to-mycelium transition of Yarrowia lipolytica induced by a shift in
      pH of the medium. As controls, yeast and mycelium monomorphic mutants were used,
      identifying by this mean a total of 61 upregulated and 165 downregulated genes
      specifically involved in dimorphism. Determination of the putative function of
      these genes was accomplished by means of BLAST analyses which showed that they
      were involved mainly in processes such as remodeling and biogenesis of the cell
      wall, membrane trafficking and N- or O-glycosylation. Some of these genes were
      identified by homology with Saccharomyces cerevisiae genes, and found to play a
      role during the dimorphic transition in both systems.

PMID- 22595081
TI  - Phosphorylation and ubiquitination of dynamin-related proteins (AtDRP3A/3B)
      synergically regulate mitochondrial proliferation during mitosis.
AB  - The balance between mitochondrial fission and fusion is disrupted during mitosis,
      but the mechanism governing this phenomenon in plant cells remains enigmatic.
      Here, we used mitochondrial matrix-localized Kaede protein (mt-Kaede) to analyze
      the dynamics of mitochondrial fission in BY-2 suspension cells. Analysis of the
      photoactivatable fluorescence of mt-Kaede suggested that the fission process is
      dominant during mitosis. This finding was confirmed by an electron microscopic
      analysis of the size distribution of mitochondria in BY-2 suspension cells at
      various stages. Cellular proteins interacting with Myc-tagged dynamin-related
      protein 3A/3B (AtDRP3A and AtDRP3B) were immunoprecipitated with anti-Myc
      antibody-conjugated beads and subsequently identified by microcapillary liquid
      chromatography-quadrupole time-of-flight mass spectrometry (CapLC Q-TOF) MS/MS.
      The identified proteins were broadly associated with cytoskeletal (microtubular),
      phosphorylation, or ubiquitination functions. Mitotic phosphorylation of
      AtDRP3A/AtDRP3B and mitochondrial fission at metaphase were inhibited by
      treatment of the cells with a CdkB/cyclin B inhibitor or a serine/threonine
      protein kinase inhibitor. The fate of AtDRP3A/3B during the cell cycle was
      followed by time-lapse imaging of the fluorescence of Dendra2-tagged AtDRP3A/3B
      after green-to-red photoconversion; this experiment showed that AtDRP3A/3B is
      partially degraded during interphase. Additionally, we found that microtubules
      are involved in mitochondrial fission during mitosis, and that mitochondria
      movement to daughter cell was limited as early as metaphase. Taken together,
      these findings suggest that mitotic phosphorylation of AtDRP3A/3B promotes
      mitochondrial fission during plant cell mitosis, and that AtDRP3A/3B is partially
      degraded at interphase, providing mechanistic insight into the mitochondrial
      morphological changes associated with cell-cycle transitions in BY-2 suspension
      cells.

PMID- 22595083
TI  - Pulmonary complications in the non-HIV immunocompromised patient.
AB  - The incidence of non-HIV immunocompromised patients is increasing. This is
      primarily due to improved immunosuppressive regimes for autoimmune diseases and
      also increases in stem cell transplantation. Pulmonary complications are a major
      cause of morbidity and mortality in these patients. Imaging is frequently used to
      assess these complications and to streamline therapies, as microbiological and/or
      pathological diagnosis can often be difficult, invasive, or protracted. This
      review provides the reader with a structured approach to interpret the imaging
      findings and differentiate between different infective and non-infective
      complications in these patients.

PMID- 22595082
TI  - Delayed response assessment with FDG-PET-CT following (chemo) radiotherapy for
      locally advanced head and neck squamous cell carcinoma.
AB  - AIMS: To analyse the diagnostic accuracy of delayed response assessment 2-[18F]
      fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography-computed tomography
      (PET-CT) following (chemo)radiation for locally advanced head and neck squamous
      cell carcinoma (HNSCC). MATERIAL AND METHODS: Forty-four consecutive patients who
      underwent a baseline and response assessment using FDG PET-CT for HNSCC following
      (chemo)radiation between August 2008 and April 2011 were identified
      retrospectively. Clinicopathological findings and serial clinical follow-up
      provided the reference standard. RESULTS: Median follow-up was 14 months (range 5
      43 months). Response assessment FDG PET-CT was performed at 16.8 weeks (inter
      quartile range 15.8-18.6 weeks). Thirty-one out of 44 (70%) response assessment
      examinations showed a complete metabolic response. Seven out of 40 (18%)
      assessable primary tumours were positive. Eight out of 41 (20%) patients with pre
      treatment nodal disease had equivocal or positive FDG uptake at response
      assessment. The sensitivity, specificity, positive predictive value (PPV), and
      negative predictive value (NPV) for primary disease and nodal disease were 100,
      89, 43, 100, and 100%, and 92, 63, and 100%, respectively. Seven patients had
      residual FDG-negative soft tissue detectable on the unenhanced CT component of
      the response assessment images; all remained disease free after clinical
      observation. Distant metastases were detected on response assessment FDG PET-CT
      in four out of the 44 patients (10%). CONCLUSION: The diagnostic accuracy of
      response assessment with FDG PET-CT performed at approximately 16 weeks post
      (chemo)radiotherapy is good. The very high NPV of a complete metabolic response
      can be used to guide management decisions. Although the PPV is limited for local
      residual disease, FDG PET-CT is a powerful screening tool for the detection of
      interim metastatic disease.

PMID- 22595084
TI  - Differences in left and right carotid intima-media thickness.

PMID- 22595085
TI  - Impact of the invasive mussel Limnoperna fortunei on glyphosate concentration in
      water.
AB  - The use of glyphosate has increased dramatically during the past years around the
      world. Microbial communities are altered when glyphosate reaches water bodies.
      The freshwater golden mussel Limnoperna fortunei is an invasive species that has
      rapidly dispersed since it was introduced in Argentina two decades ago. Mussels
      alter aquatic conditions through their filtrating activity by increasing water
      clarity and nutrient recycling. We aim to evaluate the potential capacity of the
      golden mussel to reduce glyphosate concentration in water, in laboratory
      conditions. Firstly, the evasive response of mussels to glyphosate (10, 20, and
      40 mg l-1) was evaluated and a toxicity test was carried out for these
      concentrations. A three-week experiment was then performed to assess glyphosate
      variation under mussel presence for two mussel sizes. Finally, mussels' role on
      glyphosate concentration was evaluated considering different mussel parts (living
      organisms and empty shells) through another three-week experiment. Laboratory
      experiments were performed in triplicate using 2-l microcosms. An initial
      glyphosate concentration between 16 and 19 mg l-1 was used, and when mussels or
      valvae were added, 20 organisms per aquaria were used. Samples were obtained at
      days 0, 1, 2, 4, 8, 14, and 21. Glyphosate decreased by 40% under large mussel
      presence in both experiments, and was reduced by 25% in empty shell treatments.
      We believe that part of the herbicide that disappears from the water column is
      adsorbed in valvae surface, while another proportion is being mineralized by
      microbial communities in shells' biofilm. The mechanisms by which living mussels
      increase glyphosate dissipation would be degradation, possibly mediated by
      bacteria associated to mussel's metabolism. Glyphosate half-life depended on
      mussel and valvae presence and varied with mussel size. L. fortunei presence
      (either alive or as empty valvae) alters glyphosate concentration in water. We
      provide preliminary observations from laboratory experiments, with strong
      potential ecological consequences, about two stressors that could be acting
      jointly on the environment.

PMID- 22595086
TI  - Discovering context-specific relationships from biological literature by using
      multi-level context terms.
AB  - BACKGROUND: The Swanson's ABC model is powerful to infer hidden relationships
      buried in biological literature. However, the model is inadequate to infer
      relations with context information. In addition, the model generates a very large
      amount of candidates from biological text, and it is a semi-automatic, labor
      intensive technique requiring human expert's manual input. To tackle these
      problems, we incorporate context terms to infer relations between AB interactions
      and BC interactions. METHODS: We propose 3 steps to discover meaningful hidden
      relationships between drugs and diseases: 1) multi-level (gene, drug, disease,
      symptom) entity recognition, 2) interaction extraction (drug-gene, gene-disease)
      from literature, 3) context vector based similarity score calculation.
      Subsequently, we evaluate our hypothesis with the datasets of the "Alzheimer's
      disease" related 77,711 PubMed abstracts. As golden standards, PharmGKB and CTD
      databases are used. Evaluation is conducted in 2 ways: first, comparing precision
      of the proposed method and the previous method and second, analysing top 10
      ranked results to examine whether highly ranked interactions are truly meaningful
      or not. RESULTS: The results indicate that context-based relation inference
      achieved better precision than the previous ABC model approach. The literature
      analysis also shows that interactions inferred by the context-based approach are
      more meaningful than interactions by the previous ABC model. CONCLUSIONS: We
      propose a novel interaction inference technique that incorporates context term
      vectors into the ABC model to discover meaningful hidden relationships. By
      utilizing multi-level context terms, our model shows better performance than the
      previous ABC model.

PMID- 22595087
TI  - Fast PCA for processing calcium-imaging data from the brain of Drosophila
      melanogaster.
AB  - BACKGROUND: The calcium-imaging technique allows us to record movies of brain
      activity in the antennal lobe of the fruitfly Drosophila melanogaster, a brain
      compartment dedicated to information about odors. Signal processing, e.g. with
      source separation techniques, can be slow on the large movie datasets. METHOD: We
      have developed an approximate Principal Component Analysis (PCA) for fast
      dimensionality reduction. The method samples relevant pixels from the movies,
      such that PCA can be performed on a smaller matrix. Utilising a priori knowledge
      about the nature of the data, we minimise the risk of missing important pixels.
      RESULTS: Our method allows for fast approximate computation of PCA with adaptive
      resolution and running time. Utilising a priori knowledge about the data enables
      us to concentrate more biological signals in a small pixel sample than a general
      sampling method based on vector norms. CONCLUSIONS: Fast dimensionality reduction
      with approximate PCA removes a computational bottleneck and leads to running time
      improvements for subsequent algorithms. Once in PCA space, we can efficiently
      perform source separation, e.g to detect biological signals in the movies or to
      remove artifacts.

PMID- 22595088
TI  - ASCOT: a text mining-based web-service for efficient search and assisted creation
      of clinical trials.
AB  - Clinical trials are mandatory protocols describing medical research on humans and
      among the most valuable sources of medical practice evidence. Searching for
      trials relevant to some query is laborious due to the immense number of existing
      protocols. Apart from search, writing new trials includes composing detailed
      eligibility criteria, which might be time-consuming, especially for new
      researchers. In this paper we present ASCOT, an efficient search application
      customised for clinical trials. ASCOT uses text mining and data mining methods to
      enrich clinical trials with metadata, that in turn serve as effective tools to
      narrow down search. In addition, ASCOT integrates a component for recommending
      eligibility criteria based on a set of selected protocols.

PMID- 22595089
TI  - Detecting modification of biomedical events using a deep parsing approach.
AB  - BACKGROUND: This work describes a system for identifying event mentions in bio
      molecular research abstracts that are either speculative (e.g. analysis of
      IkappaBalpha phosphorylation, where it is not specified whether phosphorylation
      did or did not occur) or negated (e.g. inhibition of IkappaBalpha
      phosphorylation, where phosphorylation did not occur). The data comes from a
      standard dataset created for the BioNLP 2009 Shared Task. The system uses a
      machine-learning approach, where the features used for classification are a
      combination of shallow features derived from the words of the sentences and more
      complex features based on the semantic outputs produced by a deep parser. METHOD:
      To detect event modification, we use a Maximum Entropy learner with features
      extracted from the data relative to the trigger words of the events. The shallow
      features are bag-of-words features based on a small sliding context window of 3-4
      tokens on either side of the trigger word. The deep parser features are derived
      from parses produced by the English Resource Grammar and the RASP parser. The
      outputs of these parsers are converted into the Minimal Recursion Semantics
      formalism, and from this, we extract features motivated by linguistics and the
      data itself. All of these features are combined to create training or test data
      for the machine learning algorithm. RESULTS: Over the test data, our methods
      produce approximately a 4% absolute increase in F-score for detection of event
      modification compared to a baseline based only on the shallow bag-of-words
      features. CONCLUSIONS: Our results indicate that grammar-based techniques can
      enhance the accuracy of methods for detecting event modification.

PMID- 22595091
TI  - Data mining of audiology patient records: factors influencing the choice of
      hearing aid type.
AB  - BACKGROUND: This paper describes the analysis of a database of over 180,000
      patient records, collected from over 23,000 patients, by the hearing aid clinic
      at James Cook University Hospital in Middlesbrough, UK. These records consist of
      audiograms (graphs of the faintest sounds audible to the patient at six different
      pitches), categorical data (such as age, gender, diagnosis and hearing aid type)
      and brief free text notes made by the technicians. This data is mined to
      determine which factors contribute to the decision to fit a BTE (worn behind the
      ear) hearing aid as opposed to an ITE (worn in the ear) hearing aid. METHODS:
      From PCA (principal component analysis) four main audiogram types are determined,
      and are related to the type of hearing aid chosen. The effects of age, gender,
      diagnosis, masker, mould and individual audiogram frequencies are combined into a
      single model by means of logistic regression. Some significant keywords are also
      discovered in the free text fields by using the chi-squared (chi(2)) test, which
      can also be used in the model. The final model can act a decision support tool to
      help decide whether an individual patient should be offered a BTE or an ITE
      hearing aid. RESULTS: The final model was tested using 5-fold cross validation,
      and was able to replicate the decisions of audiologists whether to fit an ITE or
      a BTE hearing aid with precision in the range 0.79 to 0.87. CONCLUSIONS: A
      decision support system was produced to predict the type of hearing aid which
      should be prescribed, with an explanation facility explaining how that decision
      was arrived at. This system should prove useful in providing a "second opinion"
      for audiologists.

PMID- 22595090
TI  - Semantic text mining support for lignocellulose research.
AB  - BACKGROUND: Biofuels produced from biomass are considered to be promising
      sustainable alternatives to fossil fuels. The conversion of lignocellulose into
      fermentable sugars for biofuels production requires the use of enzyme cocktails
      that can efficiently and economically hydrolyze lignocellulosic biomass. As many
      fungi naturally break down lignocellulose, the identification and
      characterization of the enzymes involved is a key challenge in the research and
      development of biomass-derived products and fuels. One approach to meeting this
      challenge is to mine the rapidly-expanding repertoire of microbial genomes for
      enzymes with the appropriate catalytic properties. RESULTS: Semantic
      technologies, including natural language processing, ontologies, semantic Web
      services and Web-based collaboration tools, promise to support users in handling
      complex data, thereby facilitating knowledge-intensive tasks. An ongoing
      challenge is to select the appropriate technologies and combine them in a
      coherent system that brings measurable improvements to the users. We present our
      ongoing development of a semantic infrastructure in support of genomics-based
      lignocellulose research. Part of this effort is the automated curation of
      knowledge from information on fungal enzymes that is available in the literature
      and genome resources. CONCLUSIONS: Working closely with fungal biology
      researchers who manually curate the existing literature, we developed ontological
      natural language processing pipelines integrated in a Web-based interface to
      assist them in two main tasks: mining the literature for relevant knowledge, and
      at the same time providing rich and semantically linked information.

PMID- 22595092
TI  - BOSS: context-enhanced search for biomedical objects.
AB  - BACKGROUND: There exist many academic search solutions and most of them can be
      put on either ends of spectrum: general-purpose search and domain-specific "deep"
      search systems. The general-purpose search systems, such as PubMed, offer
      flexible query interface, but churn out a list of matching documents that users
      have to go through the results in order to find the answers to their queries. On
      the other hand, the "deep" search systems, such as PPI Finder and iHOP, return
      the precompiled results in a structured way. Their results, however, are often
      found only within some predefined contexts. In order to alleviate these problems,
      we introduce a new search engine, BOSS, Biomedical Object Search System. METHODS:
      Unlike the conventional search systems, BOSS indexes segments, rather than
      documents. A segment refers to a Maximal Coherent Semantic Unit (MCSU) such as
      phrase, clause or sentence that is semantically coherent in the given context
      (e.g., biomedical objects or their relations). For a user query, BOSS finds all
      matching segments, identifies the objects appearing in those segments, and
      aggregates the segments for each object. Finally, it returns the ranked list of
      the objects along with their matching segments. RESULTS: The working prototype of
      BOSS is available at http://boss.korea.ac.kr. The current version of BOSS has
      indexed abstracts of more than 20 million articles published during last 16 years
      from 1996 to 2011 across all science disciplines. CONCLUSION: BOSS fills the gap
      between either ends of the spectrum by allowing users to pose context-free
      queries and by returning a structured set of results. Furthermore, BOSS exhibits
      the characteristic of good scalability, just as with conventional document search
      engines, because it is designed to use a standard document-indexing model with
      minimal modifications. Considering the features, BOSS notches up the
      technological level of traditional solutions for search on biomedical
      information.

PMID- 22595093
TI  - Nitrification performance and microbial ecology of nitrifying bacteria in a full
      scale membrane bioreactor treating TFT-LCD wastewater.
AB  - This study investigated nitrification performance and nitrifying community in one
      full-scale membrane bioreactor (MBR) treating TFT-LCD wastewater. For the A/O MBR
      system treating monoethanolamine (MEA) and dimethyl sulfoxide (DMSO), no
      nitrification was observed, due presumably to high organic loading, high
      colloidal COD, low DO, and low hydraulic retention time (HRT) conditions. By
      including additional A/O or O/A tanks, the A/O/A/O MBR and the O/A/O MBR were
      able to perform successful nitrification. The real-time PCR results for
      quantification of nitrifying populations showed a high correlation to
      nitrification performance, and can be a good indicator of stable nitrification.
      Terminal restriction fragment length polymorphism (T-RFLP) results of functional
      gene, amoA, suggest that Nitrosomonas oligotropha-like AOB seemed to be important
      to a good nitrification in the MBR system. In the MBR system, Nitrobacter- and
      Nitrospira-like NOB were both abundant, but the low nitrite environment is likely
      to promote the growth of Nitrospira-like NOB.

PMID- 22595094
TI  - Preparation of activated carbon by microwave heating of langsat (Lansium
      domesticum) empty fruit bunch waste.
AB  - The feasibility of langsat empty fruit bunch waste for preparation of activated
      carbon (EFBLAC) by microwave-induced activation was explored. Activation with
      NaOH at the IR ratio of 1.25, microwave power of 600 W for 6 min produced EFBLAC
      with a carbon yield of 81.31% and adsorption uptake for MB of 302.48 mg/g. Pore
      structural analysis, scanning electron microscopy and Fourier transform infrared
      spectroscopy demonstrated the physical and chemical characteristics of EFBLAC.
      Equilibrium data were best described by the Langmuir isotherm, with a monolayer
      adsorption capacity of 402.06 mg/g, and the adsorption kinetics was well fitted
      to the pseudo-second-order equation. The findings revealed the potential to
      prepare high quality activated carbon from langsat empty fruit bunch waste by
      microwave irradiation.

PMID- 22595095
TI  - Alteration of the biomass composition of Arthrospira (Spirulina) platensis under
      various amounts of limited phosphorus.
AB  - In this study the biomass composition alteration of the cyanobacterium
      Arthrospira (Spirulina) platensis under various amounts of limited phosphorus is
      studied. It was observed that the alteration of the compounds of the biomass
      occurred gradually as the phosphorus became limited. Carbohydrates and lipids
      increased from about 9% up to 65% and from about 4.9% up to 7.5%, respectively,
      while proteins decreased from about 46.5% to 25% as the phosphorus became
      limited. The increasing of carbohydrates and lipids in addition to the decrease
      of proteins resulted to an increase of the carbon to nitrogen (C/N) ratio from
      about 4.6 to 12.2.

PMID- 22595096
TI  - Biodiesel production from palm oil using calcined waste animal bone as catalyst.
AB  - Waste animal bones was employed as a cost effective catalyst for the
      transesterification of palm oil. The catalyst was calcined at different
      temperatures to transform the calcium phosphate in the bones to hydroxyapatite
      and 800  degrees C was found to give the best yield of biodiesel. The catalyst
      was characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD),
      energy dispersive spectrometry (EDS) and Fourier transform infrared spectrometry
      (FT-IR). Under the optimal reaction conditions of 20 wt.% of catalyst, 1:18 oil
      to methanol molar ratio, 200 rpm of stirring of reactants and at a temperature of
      65  degrees C, the methyl ester conversion was 96.78% and it was achieved in 4h.
      The catalyst performed equally well as the laboratory-grade CaO. Animal bone is
      therefore a useful raw material for the production of a cheap catalyst for
      transesterification.

PMID- 22595098
TI  - Molecular approaches for ameliorating microbial xylanases.
AB  - In industrial processes, chemical catalysis is being replaced by enzyme
      catalysis, since the latter is environmentally benign, non-persistent and cost
      effective. Microbial xylanases have significant applications in textile, baking,
      food and feed industries, and in paper and pulp industries for reducing the
      chlorine requirement. The hazardous chlorine required for bleaching can be
      reduced up to 25-30% by including an enzymatic step in the pulp bleaching
      process. The paper pulp bleaching requires xylanases that are active at alkaline
      pH and elevated temperatures. The enzymes from the cultured microbes do not
      perform optimally in the paper industry due to their inadequate stability under
      the process conditions of high temperature and alkaline pH. This review,
      therefore, deals with the rationale of molecular approaches such as protein
      engineering for designing xylanases with improved characteristics to suit the
      process conditions in industries, and prospects and problems.

PMID- 22595097
TI  - A pilot investigation into membrane bioreactor using mesh filter for treating low
      strength municipal wastewater.
AB  - A pilot-scale submerged membrane bioreactor (MBR) using nylon mesh as filter was
      investigated for treatment of low-strength municipal wastewater (average influent
      COD=145.7+/-59.9 mg/L). During the operation, biomass was effectively retained by
      the nylon mesh with biofilm attached, and a low effluent turbidity of below 2 NTU
      was obtained. The average COD and NH(4)(+)-N removal efficiencies reached 86.3%
      and 98.1%, respectively, at a hydraulic retention time of 5 h. A sludge
      concentration of 4.15+/-0.15 g/L was maintained in the system without excess
      sludge discharge, attributed to the prolonged solid retention time and low
      organic loading rate. The low sludge concentration was also beneficial for
      mitigating the filter fouling. Thus, this mesh filter MBR provides a low-cost,
      efficient and simple approach to treat municipal wastewater, and shows a high
      potential for application in rural and sparsely populated areas.

PMID- 22595099
TI  - Potential of Ceiba pentandra (L.) Gaertn. (kapok fiber) as a resource for second
      generation bioethanol: effect of various simple pretreatment methods on sugar
      production.
AB  - The importance of bioethanol currently has increased tremendously as it can
      reduce the total dependency on fossil-fuels, especially gasoline, in the
      transportation sector. In this study, Ceiba pentandra (kapok fiber) was
      introduced as a new resource for bioethanol production. The results of chemical
      composition analysis showed that the cellulose (alpha- and beta-) contents were
      50.7%. The glucose composition of the fiber was 59.8%. The high glucose content
      indicated that kapok fiber is a potential substrate for bioethanol production.
      However, without a pretreatment, the kapok fiber only yielded 0.8% of reducing
      sugar by enzymatic hydrolysis. Thus, it is necessary to pre-treat the kapok fiber
      prior to hydrolysis. Taking into account environmentally friendliness, only
      simple pretreatments with minimum chemical or energy consumption was considered.
      It was interesting to see that by adopting merely water, acid and alkaline
      pretreatments, the yield of reducing sugar was increased to 39.1%, 85.2% and
      >100%, respectively.

PMID- 22595100
TI  - Removal of inhibitors from pre-hydrolysis liquor of kraft-based dissolving pulp
      production process using adsorption and flocculation processes.
AB  - A process for removing inhibitors from pre-hydrolysis liquor (PHL) of a kraft
      based dissolving pulp production process by adsorption and flocculation, and the
      characteristics of this process were studied. In this process, industrially
      produced PHL was treated with unmodified and oxidized activated carbon as an
      absorbent and polydiallyldimethylammonium chloride (PDADMAC) as a flocculant. The
      overall removal of lignin and furfural in the developed process was 83.3% and
      100%, respectively, while that of hemicelluloses was 32.7%. These results
      confirmed that the developed process can remove inhibitors from PHL prior to
      producing value-added products, e.g. ethanol and xylitol via fermentation.

PMID- 22595102
TI  - Poor professionalism identified through investigation of unsolicited healthcare
      complaints.
AB  - AIM: To determine whether analysis of unsolicited healthcare complaints
      specifically focusing on unprofessional behaviour can provide additional
      information from the patients' perspective. METHODS: A qualitative study with
      content analysis of healthcare complaints and associated judgements using
      complaints filed from 2004 to 2009 at the complaints committee of a tertiary
      referral centre. Subsequent comparison of the resulting categories of poor
      professionalism to categories perceived relevant by physicians in a previous
      study was performed. RESULTS: 137 complaints (98%) yielded 46 different
      unprofessional behaviours grouped into 18 categories. The element 'perceived
      medical complications and error' occurred most commonly (n=77), followed by
      'having to wait for care' and 'insufficient or unclear clarification' (n=52,
      n=48, respectively). The combined non-cognitive elements of professionalism
      (especially aspects of communication) were far more prominently discussed than
      cognitive issues (knowledge/skills) related to medical error. Most categories of
      professionalism elements were considered important by physicians but,
      nevertheless, were identified in patient complaints analysis. Some issues (eg,
      'altruism', 'appearance', 'keeping distance/respecting boundaries with patients')
      were not perceived as problematic by patients and/or relatives, while mentioned
      by physicians. Conversely, eight categories of poor professionalism revealed from
      complaint analysis (eg, 'having to wait for care', 'lack of continuity of care'
      and 'lack of shared decision making') were not considered essential by
      physicians. CONCLUSIONS: The vast majority of unprofessional behaviour identified
      related to non-cognitive, professionalism aspects of care. Complaints pertaining
      to unsatisfactory communication were especially noticeable. Incongruence is noted
      between the physicians' and the patients' perception of actual care.

PMID- 22595101
TI  - Lab scale experiments using a submerged MBR under thermophilic aerobic conditions
      for the treatment of paper mill deinking wastewater.
AB  - This paper describes the results of laboratory experiments using a thermophilic
      aerobic MBR (TMBR) at 50  degrees C. An innovative use of submerged flat-sheet
      MBR modules to treat circuit wastewater from the paper industry was studied. Two
      experiments were conducted with a flux of 8-13 L/m(2)/h without chemical membrane
      cleaning. COD and BOD(5) elimination rates were 83% and 99%, respectively.
      Calcium was reduced from 110 to 180 mg/L in the inflow to 35-60 mg/L in the
      permeate. However, only negligible membrane scaling occurred. The observed sludge
      yield was very low and amounted to 0.07-0.29 g MLSS/g COD(eliminated).
      Consequently, the nutrient supply of ammonia and phosphate can be lower compared
      to a mesophilic process. Molecular-biological FISH analysis revealed a likewise
      high diversity of microorganisms in the TMBR compared to the mesophilic sludge
      used for start-up. Furthermore, ammonia-oxidising bacteria were detected at
      thermophilic operation.

PMID- 22595103
TI  - Frequency and distribution of radiolucent jaw lesions: a retrospective analysis
      of 9,723 cases.
AB  - OBJECTIVES: Practitioners should be aware of the occurrence rate and usual
      location of radiolucent jaw lesions. The aims of this study were to examine the
      frequency and location of radiolucent jaw lesions, including apical granulomas,
      apical cysts, keratocystic odontogenic tumors (KOTs), central giant cell lesions
      (CGCLs), ameloblastomas, and metastatic lesions, that were submitted for biopsy
      along with associated demographics. METHODS: Biopsy diagnoses from 9,723 lesions
      (submitted between 1992 and 2006) were included in this study. Data on lesion
      location as well as patient demographics were evaluated. RESULTS: Thirty types of
      radiolucent jaw lesions were classified. Nonhealing apical granulomas (40.4%) and
      cysts (33.1%) occurred at similar rates and together totaled 73% of all biopsied
      lesions. The majority of reported granulomas and cysts occurred in the anterior
      maxilla (>36% in each category). The frequency of KOTs (8.8%), CGCLs (1.3%),
      ameloblastomas (1.2%), and metastatic lesions (<1%) are to be noted along with
      their location, which was predominately in the posterior mandible. The occurrence
      of apical cysts, ameloblastomas, KOTs, and metastatic lesions were seen slightly
      more in men, at 56%, 54%, 55%, and 68%, respectively. The occurrence of CGCLs was
      seen slightly more in women at 56%, whereas apical granulomas were equally
      present in men and women. CONCLUSIONS: Most nonhealing lesions submitted for
      biopsy were classified as granulomas or cysts (73%) often from the anterior
      maxillary jaw. Nonhealing radiolucent jaw lesions other than granulomas or cysts
      were reported over 20% of the time and may have more severe pathological
      implications, suggesting the value of differential diagnoses.

PMID- 22595104
TI  - Effect of platelet concentrate on quality of life after periradicular surgery: a
      randomized clinical study.
AB  - INTRODUCTION: Control of postoperative discomfort might enhance the patient's
      quality of life and treatment acceptance. The aim of the present randomized
      single-blind study was to evaluate whether the use of platelet concentrate during
      endodontic surgery might have a favorable impact on pain and other factors
      related to patient's quality of life during the first week after surgery.
      METHODS: Eighteen patients with periapical lesion were treated with modern
      endodontic surgical procedure (control group). In another 18 patients, in adjunct
      to surgical procedure, platelet concentrate was applied on the root end in liquid
      form, within the bone defect in clot form, and over the suture in liquid form
      (test group). All patients completed a questionnaire for evaluation of main
      symptoms and daily activities during the first week after surgery. The outcomes
      of the questionnaires of the 2 groups were statistically compared. RESULTS: The
      test group showed significantly less pain and swelling, fewer analgesics taken,
      and improved functional activities as compared with the control group.
      CONCLUSIONS: The adjunct of platelet concentrate to the endodontic surgical
      procedure produced significant beneficial effect to patients' quality of life
      during the early postoperative stage.

PMID- 22595105
TI  - Correlation between clinical/radiographic features and inflammatory cytokine
      networks produced by macrophages stimulated with endodontic content.
AB  - INTRODUCTION: Macrophages are highly activated by endodontic contents. This study
      investigated the correlation between different clinical signs/symptoms and
      radiographic features according to the levels of interleukin (IL)-1beta, tumor
      necrosis factor alpha (TNF-alpha), IL-6, IL-10, prostaglandin E(2) (PGE(2)), and
      their networks produced by endodontic content-stimulated macrophages collected
      from primary endodontic infection with apical periodontitis (PEIAP). METHODS:
      Samples were taken from 21 root canals with PEIAP by using paper points. The
      presence of exudate (EX), pain on palpation (POP), tenderness to percussion
      (TTP), and the size of the radiographic lesion (SRL) were recorded. Polymerase
      chain reaction (16S rDNA) was used for bacterial detection and limulus amebocyte
      lysate (LAL) assay for endotoxin measurement. Raw 264.7 macrophages were
      stimulated with bacterial contents during 24 hs. The amounts of IL-1beta, TNF
      alpha, IL-6, IL-10 and PGE(2) were measured by enzyme-linked immunosorbent assay.
      Log-based data were correlated by multiple logistic regression (P < .05).
      RESULTS: Bacteria and endotoxin were detected in 100% of the samples. IL-6 and
      TNF-alpha were positively correlated with SRL and EX, respectively (P < .05).
      Clinical signs/symptoms and radiographic findings were set as dependent variables
      for EX-positive correlations between PGE(2), IL-1beta, and TNF-alpha (P < .05),
      whereas IL-6 and PGE(2) were positively correlated to each other in POP but
      negatively correlated in SRL (P < .05). When POP and TTP-POP were set as
      dependent variables, different cytokine networks were found. CONCLUSIONS: Our
      findings suggest different roles for each cytokine in the development of apical
      periodontitis, whose effects of overlapping networks depend on the signs/symptoms
      and radiographic features found in endodontic infection.

PMID- 22595106
TI  - Differential expression of microRNAs in normal and inflamed human pulps.
AB  - INTRODUCTION: MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene
      expression via posttranscriptional repression. They are critical to normal
      cellular function, and bioinformatic predictions indicate that at least one third
      of all messenger RNAs might be regulated by miRNAs. Although both the innate and
      adaptive immune responses are known to be regulated by miRNAs, their role in
      regulating endodontic disease has yet to be explored. The purpose of this study
      was to examine the differential expression of miRNAs in normal and inflamed human
      dental pulps and to explore their functional gene targets. METHODS: After
      obtaining informed consent, we collected normal and inflamed human pulps (N =
      30). Microarray and molecular biology techniques were then used for gene
      profiling and identifying functional gene targets. RESULTS: Of the 335 human
      miRNAs identified in the pulp tissues, 3 miRNAs, miR-150*, miR-584, and miR-766,
      were significantly up-regulated in inflamed pulps as compared with normal pulps
      (P < .003). Thirty-three miRNAs were down-regulated in the inflamed pulps (P <
      .003). The false discovery rate for these findings is estimated to be
      approximately 5%. The potential gene targets for these miRNAs include
      proinflammatory cytokines as well as other key mediators of the immune and
      inflammatory response to infection. CONCLUSIONS: Our data identify differential
      expression of miRNAs in healthy and diseased human dental pulps. These findings
      highlight the intricate and specific roles of miRNA in inflammation and immunity,
      both of which are key aspects of pulpal pathology.

PMID- 22595107
TI  - Comparative evaluation of 1.8 mL and 3.6 mL of 2% lidocaine with 1:200,000
      epinephrine for inferior alveolar nerve block in patients with irreversible
      pulpitis: a prospective, randomized single-blind study.
AB  - INTRODUCTION: There is a decrease in the anesthetic efficacy of inferior alveolar
      nerve blocks in patients with irreversible pulpitis. It was hypothesized that the
      increasing the volume of anesthetic solution may improve the success rates of
      dental pulp anesthesia in patients with pulpal pain. METHODS: Fifty-five adult
      volunteers, actively experiencing pain, participated in this prospective,
      randomized, single-blind study. The patients were divided into 2 groups on a
      random basis and received an inferior alveolar nerve block with either 1.8 mL or
      3.6 mL of 2% lidocaine with 1:200,000 epinephrine. Endodontic access preparation
      was initiated after 15 minutes of the initial IANB. Pain during treatment was
      recorded using the Heft-Parker visual analog scale (HP VAS). The primary outcome
      measure, and the definition of "success," was the ability to undertake pulp
      access and canal instrumentation with no or mild pain (HP VAS score <55 mm).
      Statistical analysis was performed using the chi-square test. RESULTS: All
      patients included in the final analysis had profound lip anesthesia. There were
      no significant differences in sex, age, or preoperative pain scores of the
      experimental groups. IANBs of 1.8 mL lidocaine with epinephrine had a success
      rate of 26%, whereas the administration of 3.6 mL had a 54% success rate. The
      difference was statistically significant. CONCLUSIONS: Increasing the volume of
      2% lidocaine to 3.6 mL improved the success rate as compared with 1.8 mL but did
      not give a clinical success rates of 100%.

PMID- 22595108
TI  - Simvastatin alleviates the progression of periapical lesions by modulating
      autophagy and apoptosis in osteoblasts.
AB  - INTRODUCTION: Autophagy is a process for recycling intracellular organelles as a
      survival mechanism. Apoptosis has important biological roles in the pathogenesis
      of many diseases. This study elucidated the effect of simvastatin on
      autophagy/apoptosis in MC3T3E1 murine osteoblastic cells and also the
      significance of this action on the progression of induced rat apical
      periodontitis. METHODS: We examined the H2O2-stimulated expression of LC3-II (an
      autophagy marker) and poly (adenosine phosphate ribose) polymerase (PARP)
      fragmentation (an apoptosis marker) in MC3T3E1 by Western analysis. In a rat
      model of induced apical periodontitis, the relation between disease progression
      and osteoblastic expression of Beclin-1 (an autophagy marker) and terminal
      deoxyuridine triphosphate nick end-labeling (an apoptosis marker) was studied by
      radiographic and immunohistochemistry analyses. RESULTS: Western blot showed
      elevated levels of LC3-II and PARP cleavage after H2O2 treatment. An autophagy
      inhibitor 3-methyladenine promoted whereas rapamycin (an autophagy enhancer)
      diminished H2O2-induced PARP cleavage. Simvastatin enhanced H2O2-induced LC3-II
      formation and simultaneously decreased PARP fragmentation. Radiography and
      immunohistopathology demonstrated that simvastatin reduced the number of
      apoptotic osteoblasts and the extension of periapical lesions in rats. The number
      of Beclin-1-synthesizing osteoblasts also increased markedly after simvastatin
      treatment. CONCLUSIONS: We found a negative relation between autophagy and
      apoptosis in osteoblastic cells. In addition, simvastatin suppressed apoptosis
      and enhanced autophagy both in vitro and in vivo. Our data implied that
      simvastain might alleviate the progression of apical periodontitis by promoting
      autophagy to protect osteoblasts from turning apoptotic.

PMID- 22595109
TI  - The levels of vascular endothelial growth factor and bone morphogenetic protein 2
      in dental pulp tissue of healthy and diabetic patients.
AB  - INTRODUCTION: Vascular endothelial growth factor (VEGF) and bone morphogenetic
      protein 2 (BMP 2) are growth factors (GFs) identified within the dentine-pulp
      complex and involved into the cellular events connected to the pulp-healing
      response. It is well established that the expression of these GFs is increased in
      different tissues in diabetes mellitus. Because there are no data concerning the
      levels of VEGF and BMP 2 in human dental pulp, the aim of present study was to
      quantify VEGF and BMP 2 levels in intact dental pulp and dental pulp that
      underwent reactive dentinogenesis in healthy and diabetic human subjects.
      METHODS: The study was conducted on 28 healthy and 28 subjects with controlled
      diabetes type II who underwent pulp extirpation as a part of prosthetic
      rehabilitation. Pulp were collected from intact teeth and teeth treated by
      indirect pulp capping. The levels of VEGF and BMP 2 were determined in the pulp
      tissue lysates with enzyme-linked immunosorbent assay. RESULTS: The levels of
      VEGF and BMP 2 were significantly higher in intact teeth pulp of diabetic than in
      healthy subjects. The concentrations of these GFs were significantly lowered in
      teeth with indirect pulp capping both in healthy and diabetic persons.
      Furthermore, VEGF and BMP 2 levels were in strong positive correlation.
      CONCLUSIONS: Similar changes in the levels of VEGF and BMP 2 in intact and
      treated teeth of healthy and diabetic patients could be suggestive of associated
      roles of these GFs in responses of healthy and diabetic dental pulp.

PMID- 22595110
TI  - Lysyl oxidase and the lysyl oxidase-like protein modulate odontoblastic
      differentiation of human dental pulp cells.
AB  - INTRODUCTION: The lysyl oxidase (LOX) family is an emerging family of amine
      oxidases responsible for the formation of collagen fibrils in the extracellular
      matrix. To date, 5 LOX family genes have been identified in humans, encoding LOX
      and LOX-like proteins (LOXL, LOXL2, LOXL3, and LOXL4). The goal of this study was
      to evaluate the expression and function of the LOX family genes in odontoblastic
      differentiation of human dental pulp (HDP) cells. METHODS: Expression of the LOX
      family genes was assessed by reverse transcriptase polymerase chain reaction
      analysis, and the amine oxidase activity of HDP cells was evaluated by peroxidase
      coupled fluorometric assays. Mineral nodule formation and expression of
      odontoblastic marker genes were assessed in the presence and absence of specific
      small interfering RNAs (siRNAs) of the LOX family genes. RESULTS: Among the LOX
      family genes, only LOX and LOXL showed prominent expression during odontoblastic
      differentiation of HDP cells. Suppression of LOX and LOXL expression by siRNA
      induced interference substantially decreased the amine oxidase activity of the
      differentiating HDP cells. Furthermore, interference of LOX and LOXL expression
      inhibited mineral nodule formation and expression of odontoblastic marker genes
      during odontoblastic differentiation of HDP cells. CONCLUSIONS: These findings
      show for the first time that the LOX- and LOXL-mediated organization of collagen
      fibrils in extracellular matrices of HDP cells might be an important regulator
      for odontoblastic differentiation of HDP cells.

PMID- 22595111
TI  - Regulation of vascular cell adhesion molecule-1 in dental pulp cells by
      interleukin-1beta: the role of prostanoids.
AB  - INTRODUCTION: Vascular cell adhesion molecule (VCAM-1) plays a critical role in
      the inflammatory processes by stimulating the recruitment, extravasation, and
      migration of leukocytes. Its expression and regulation in the dental pulp is not
      well elucidated. METHODS: Primary dental pulp cells were exposed to prostaglandin
      E(2) (PGE(2)), prostaglandin F(2alpha) (PGF(2alpha)), or interleukin 1beta (IL
      1beta) with/without aspirin. VCAM-1 messenger RNA expression was analyzed by
      reverse transcriptase-polymerase chain reaction. Soluble VCAM-1 (sVCAM-1) in the
      culture medium was determined by enzyme-linked immunosorbent assay, and the
      number of viable cells was estimated by (3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide (MTT) assay. RESULTS: IL-1beta induced VCAM-1 gene
      expression of pulp cells. IL-1beta also stimulated sVCAM-1 production. The IL
      1beta-induced sVCAM-1 production was not inhibited but rather enhanced by
      aspirin, a cyclooxygenase (COX) inhibitor. PGE(2) and PGF(2alpha) decreased the
      VCAM-1 expression and sVCAM-1 production of pulp cells. U0126 (1,4-diamino-2,3
      dicyano-1,4-bis[2-aminophenylthio]butadiene), a mitogen-activated protein kinase
      kinase (MEK) inhibitor, attenuated IL-1beta-induced sVCAM-1 production. However,
      no marked cytotoxicity was noted in these experimental conditions as analyzed by
      MTT assay. CONCLUSIONS: IL-1beta may be involved in the pulpal inflammatory
      processes via stimulation of VCAM-1 expression and sVCAM-1 production. This event
      is not mediated by COX activation and prostanoid production but is associated
      with MEK signaling. PGE(2) and PGF(2alpha) may potentially regulate inflammatory
      processes by the inhibition of VCAM-1.

PMID- 22595112
TI  - Cytidine-phosphate-guanosine oligonucleotides induce interleukin-8 production
      through activation of TLR9, MyD88, NF-kappaB, and ERK pathways in odontoblast
      cells.
AB  - INTRODUCTION: Odontoblasts are involved in innate immunity against invading
      microorganisms. However, the mechanisms of host inflammatory responses to
      bacterial DNA in odontoblasts are not fully understood. The purpose of this study
      was to investigate whether microbial cytidine-phosphate-guanosine (CpG) DNA
      influences interleukin-8 (IL-8) expression in odontoblasts and the signaling
      pathways involved. METHODS: The effect of CpG oligonucleotide (CpG ODN) on IL-8
      mRNA and protein expression levels in the mouse odontoblast-like cell line MDPC
      23 was investigated by real-time polymerase chain reaction (PCR) analysis and
      enzyme-linked immunosorbent assay (ELISA). Whether Toll-like receptor 9 (TLR9),
      myeloid differentiation marker 88 (MyD88), nuclear factor kappa B (NF-kappaB), or
      mitogen-activated protein kinase (MAPK) pathways were involved in the CpG ODN
      induced IL-8 expression was determined by examined real-time PCR, ELISA, and
      luciferase activity assay. Extracellular signal-regulated kinase (ERK) activation
      and TLR9 protein expression were measured by Western blot analysis. RESULTS:
      Exposure to CpG ODN induced significant up-regulation of IL-8 mRNA and protein in
      MDPC-23 cells. CpG ODN-induced IL-8 up-regulation was attenuated by TLR9
      inhibitor (chloroquine) and MyD88 inhibitory peptide. CpG ODN also increased the
      expression of TLR9 mRNA and protein in MDPC-23 cells. Treatment of MDPC-23 cells
      with NF-kappaB inhibitors (pyrrolidine dithiocarbamate), IkappaBalpha
      phosphorylation inhibitors (Bay 117082), or IkappaB protease inhibitor (L-1
      tosylamido-2-phenylethyl chloromethyl ketone) decreased CpG ODN-induced IL-8
      expression. Furthermore, stimulation of cells with CpG ODN enhanced kappaB
      luciferase activity, and the activity was diminished by the overexpression of
      dominant negative mutants of MyD88 and IkappaBalpha. In addition, CpG ODN-induced
      IL-8 expression was markedly suppressed by U0126, but not by SB203580 and
      SP600125. Moreover, CpG ODN activated ERK phosphorylation in a time-dependent
      manner. CONCLUSIONS: These data demonstrate that CpG ODN-induced IL-8 expression
      was mediated through TLR9, MyD88, NF-kappaB, and ERK pathways in MDPC-23 cells
      and suggest a possible role for the CpG DNA-mediated immune response in
      odontoblasts with involvement of TLR9, MyD88, and ERK pathways in this process.

PMID- 22595113
TI  - Anandamide induces matrix metalloproteinase-2 production through cannabinoid-1
      receptor and transient receptor potential vanilloid-1 in human dental pulp cells
      in culture.
AB  - INTRODUCTION: Anandamide (N-arachidonoylethanolamine [AEA]) is one of the main
      endocannabinoids. Endocannabinoids are implicated in various physiological and
      pathologic functions, inducing not only nociception but also regeneration and
      inflammation. The role of the endocannabinoid system in peripheral organs was
      recently described. The aim of this study was to investigate the effect of AEA on
      matrix metalloproteinase (MMP)-2 induction in human dental pulp cells (HPC).
      METHODS: We examined AEA-induced MMP-2 production and the expression of AEA
      receptors (cannabinoid [CB] receptor-1, CB2, and transient receptor potential
      vanilloid-1 [TRPV1]) in HPC by Western blot. MMP-2 concentrations in supernatants
      were determined by enzyme-linked immunosorbent assay. We then investigated the
      role of the AEA receptors and mitogen-activated protein kinase in AEA-induced MMP
      2 production in HPC. RESULTS: AEA significantly induced MMP-2 production in HPC.
      HPC expressed all 3 types of AEA receptor (CB1, CB2, and TRPV1). AEA-induced MMP
      2 production was blocked by CB1 or TRPV1 antagonists and by small interfering RNA
      for CB1 or TRPV1. Furthermore, c-Jun N-terminal kinase inhibitor also reduced MMP
      2 production. CONCLUSIONS: We demonstrated for the first time that AEA induced
      MMP-2 production via CB1 and TRPV1 in HPC.

PMID- 22595114
TI  - Isolation and identification of CXCR4-positive cells from human dental pulp
      cells.
AB  - INTRODUCTION: In previous studies, we found expression of stromal cell-derived
      factor-1alpha (SDF-1alpha)/CXC chemokine receptor 4 (CXCR4) in human dental pulp
      and the SDF-1alpha-CXCR4 axis might play a role in the recruitment of CXCR4
      positive dental pulp cells (CXCR4(+) DPCs) toward the damaged sites. However, the
      specific function of CXCR4(+) DPCs in the injured dental pulp was still unknown.
      The purpose of this study was to isolate CXCR4(+) DPCs from dental pulp cells in
      vitro to pave the way for further study of their characteristics. METHODS:
      CXCR4(+) DPCs were isolated with magnetic-activated cell sorting (MACS). Freshly
      isolated CXCR4(+) DPCs were identified by immunohistochemistry with light
      microscopy or confocal microscopy. Then the phenotypes CXCR4, stromal cell
      surface marker-1 (STRO-1), CD146, and CD34 in 3 groups (ie, CXCR4(+) DPCs, CXCR4(
      ) DPCs, or non-sorted DPCs) were analyzed by flow cytometry after they were
      cultured and expanded in vitro. RESULTS: The results indicated the isolated
      subpopulation of DPCs was enriched with CXCR4(+) DPCs, and the positive rates of
      STRO-1 and CD146 in CXCR4(+) DPCs group were higher than CXCR4(-) DPCs or non
      sorted DPCs groups (P < .05). There was no expression of CD34 in each group.
      CONCLUSIONS: We can isolate CXCR4(+) DPCs from DPCs with MACS and identify them
      by immunohistochemistry and flow cytometry.

PMID- 22595115
TI  - Changes in proliferation and osteogenic differentiation of stem cells from deep
      caries in vitro.
AB  - INTRODUCTION: It is suggested that dental pulp stem cells are involved in tooth
      regeneration and play an important role in maintaining pulp homeostasis.
      Previously, normal dental pulps were more widely used for experimental models
      than carious dental pulps. The aim of this study was to isolate and culture the
      dental pulp stem cells from carious and normal teeth and to evaluate stem cell
      parameters. METHODS: Pulp tissues were obtained and dissociated from normal and
      carious teeth. Single-cell suspensions were seeded into 6-well plates and
      purified by collecting multiple colonies. Normal dental pulp stem cells (DPSCs)
      and carious dental pulp stem cells (CDPSCs) were compared for morphologic
      appearance and for their capacity to differentiate into 3 lineages. Colony
      forming and MTT assays, cell cycle analysis, gene expression, and alkaline
      phosphatase activity were also evaluated. RESULTS: Stem cells were cultured
      successfully from normal and carious dental pulps. CDPSCs displayed increased
      proliferation ability compared with DPSCs. CDPSCs also showed enhanced ALP
      activity, mineralization ability, and expression of osteogenesis/dentinogenesis
      related genes. All cultures differentiated into 3 cell types. CONCLUSIONS: Our
      data suggest that caries as a local microenvironment should be taken into account
      when DPSCs are intended to be used for investigations and application.
      Furthermore, the mechanism of the underlying changes in cell properties requires
      further study.

PMID- 22595116
TI  - Toll-like receptor 2 knockout mice showed increased periapical lesion size and
      osteoclast number.
AB  - INTRODUCTION: The aim of this study was to characterize the formation and
      progression of experimentally induced periapical lesions in TLR2 knockout (TLR2
      KO) mice. METHODS: Periapical lesions were induced in molars of 28 wild type (WT)
      and 27 TLR2 KO mice. After 7, 21, and 42 days, the animals were euthanized, and
      the mandibles were subjected to histotechnical processing. Hematoxylin-eosin
      stained sections were examined under conventional light microscopy for the
      description of pulpal, apical, and periapical features and under fluorescence
      microscopy for the determination of the periapical lesion size. The subsequent
      sections were evaluated by tartrate resistant acid phosphatase histoenzymology
      (osteoclasts), Brown and Brenn staining (bacteria), and immunohistochemistry
      (RANK, RANKL, and OPG). Data were analyzed by the Mann-Whitney U and Kruskal
      Wallis tests (alpha = 0.05). RESULTS: The WT group showed significant differences
      (P < .05) in the periapical lesion size and the osteoclast number between 7 and
      42 days and between 21 and 42 days. In the TLR2 KO group, significant differences
      (P < .05) in the periapical lesion size and the osteoclast number were found
      between 7 days and the other periods. There was a significant difference (P <
      .05) between the 2 types of animal regarding the periapical lesion size, which
      was larger in the TLR2 KO animals. No significant differences (P > .05) were
      found between WT and TLR2 KO mice related to the pulpal, apical, and periapical
      features; bacteria localization; and immunohistochemical results (except for RANK
      expression). CONCLUSIONS: TLR2 KO animals developed larger periapical lesions
      with a greater number of osteoclasts, indicating the important role of this
      receptor in the host's immune and inflammatory response to root canal and
      periradicular infection.

PMID- 22595117
TI  - Quantitative determination of high-temperature requirement protein A1 and its
      possible associated molecules during induced reparative dentin formation.
AB  - INTRODUCTION: The equilibrium of inhibitors and inducers plays an important role
      in the mineralization of dentin during dentinogenesis. High-temperature
      requirement protein A1 (HtrA1) is a novel bone mineralization inhibitor involved
      in physiological and pathological bone formation. However, the expression of
      HtrA1 in tooth mineralization is unknown. The purpose of the present study was to
      investigate the localization and quantity of HtrA1 and its possible related
      molecules during induced reparative dentin formation. METHODS: Rats were randomly
      sacrificed after direct pulp capping on days 0, 7, 14, and 21. Maxillary segments
      were obtained and routinely prepared for histological analysis,
      immunohistochemistry, quantum dots-based double immunofluorescence, and CRi's
      Nuance imaging system (CRI, Woburn, MA)-based quantitative determination.
      RESULTS: The square measure values of reparative dentin significantly increased
      on day 7 and continued to increase until day 21. HtrA1, matrix Gla protein (MGP),
      nestin, and bone sialoprotein were positively stained and colocalized in the
      odontoblasts and/or odontoblast-like cells zone and reparative dentin during
      induced reparative dentin formation. The expressions of HtrA1 and MGP were
      significantly enhanced after direct pulp capping on day 7 and did not
      significantly change between days 7, 14, and day 21. Both expressions of HtrA1
      and MGP were positively correlated with the square measure values of reparative
      dentin; however, no correlation was found between the expressions of HtrA1 and
      MGP. CONCLUSIONS: HtrA1 could be observed and might possibly be involved in the
      process of reparative dentin formation associated with MGP.

PMID- 22595118
TI  - Decreased bacterial adherence and biofilm growth on surfaces coated with a
      solution of benzalkonium chloride.
AB  - INTRODUCTION: Secondary biofilm formation by oral bacteria after
      breakdown/fracture of temporary or permanent restorations imposes a challenge to
      the outcome of root canal treatment. This study focuses on benzalkonium chloride
      (BAK) coating on dentin or polystyrene surfaces and its influence on the early
      adhesion and biofilm formation by oral and root canal bacteria. METHODS:
      Microbial adhesion and biofilm growth on surfaces coated with BAK were analyzed
      qualitatively with a dentin disk model and quantitatively with a mini-flow cell
      biofilm model. Cell viability and total biovolume were analyzed by the LIVE/DEAD
      technique. The repelling effect of surfaces coated with BAK was compared with
      NaOCl. Uncoated surfaces were used as controls. RESULTS: Scanning electron
      microscope images in the dentin disk model revealed that very sparse biofilms
      were formed on NaOCl- and BAK-coated dentin surfaces. In contrast, biofilms
      formed on uncoated dentin were clearly visible as numerous irregularly
      distributed aggregates of rods and cocci. In the mini-flow cell system, confocal
      laser scanning microscope analysis confirmed that biofilms formed on NaOCl- and
      BAK-coated surfaces showed significantly less adhesion (2 hours) and biovolume
      accumulation (24 and 96 hours) compared with the uncoated controls (P < .01).
      Furthermore, cell viability assessments showed that on uncoated controls the
      viability measurements were high (>89%) as well as on BAK-coated surfaces (88%
      viable cells). However, cell viability was significantly reduced on NaOCl-coated
      surfaces (59% viable cells). CONCLUSIONS: This study illustrates that surface
      coating with a surfactant solution containing BAK does not cause cell membrane
      damage but might interfere with cell mechanisms of adhesion. Investigations into
      the clinical utility of BAK as an antibiofilm medication are warranted.

PMID- 22595119
TI  - Residual activity of chelating agents and their combinations with cetrimide on
      root canals infected with Enterococcus faecalis.
AB  - INTRODUCTION: The use of chelating agents in endodontic treatment is required to
      remove the smear layer and to achieve better disinfection within the root canal
      system. The aim of this study was to evaluate the residual antimicrobial activity
      of 17% ethylenediaminetetraacetic acid (EDTA), 7% maleic acid (MA), and 10%
      lactic acid (LA) alone and combined with 0.2% cetrimide (CTR) on infected root
      canals with Enterococcus faecalis. METHODS: Biofilms of E. faecalis were grown in
      uniradicular roots for 4 weeks. After preparation the roots were randomly divided
      into 6 groups (n = 15) according to the final irrigation regimen as follows: 5 mL
      of 17% EDTA; 5 mL of 17% EDTA + 0.2% CTR; 5 mL of 7% MA; 5 mL of 7% MA + 0.2%
      CTR; 5 mL of 10% LA; and 5 mL of 10% LA + 0.2% CTR. Samples were collected for 60
      days to denote the presence of bacterial growth. Fisher and Pearson chi(2) tests
      were applied to compare the percentages of specimens without E. faecalis regrowth
      at all the time periods. RESULTS: There were significant differences in bacterial
      regrowth between the groups with and without CTR. There were not significant
      differences over time among the 3 groups with CTR or among the 3 without CTR.
      CONCLUSIONS: The residual activity against E. faecalis of 7% MA + 0.2% CTR, 17%
      EDTA + 0.2% CTR, and 10% LA + 0.2% CTR was greater than the use of chelating
      agents alone.

PMID- 22595120
TI  - Effects of calcium silicate-based materials on collagen matrix integrity of
      mineralized dentin.
AB  - INTRODUCTION: Calcium silicate-based materials (CSMs) are used in various
      endodontic procedures. The present study examined whether prolonged contact of
      mineralized dentin with recently commercialized versions of these materials
      adversely affects dentin collagen matrix integrity. METHODS: Dentin slabs
      prepared from extracted human third molars (7 * 3 * 0.3 mm) were divided into 3
      groups on the basis of the material to which dentin was exposed (MTA Plus,
      Biodentine, untreated control dentin slabs) and the time period of exposure (24
      hours, 1, 2, and 3 months; n = 6). Hydroxyproline assay was performed on each
      group's supernatant to quantify the collagen extraction amounts of each group per
      time period. Data were analyzed with two-factor repeated-measures analysis of
      variance and Holm-Sidak pair-wise comparisons (alpha = 0.05) to determine the
      effects of material and aging time on collagen extraction. Dentin slabs from the
      3 months of aging group were demineralized for transmission electron microscopy
      examination of collagen matrix ultrastructural changes. RESULTS: Material (P =
      .002), aging time (P < .001), and their interactions (P = .007) significantly
      affected the amount of hydroxyproline (pg/mg of mineralized dentin) extracted
      from mineralized dentin and were significantly correlated by power regression
      models. Collagen degradation was identified from the surface of dentin slabs that
      were in direct contact with CSMs. CONCLUSIONS: Prolonged contact of mineralized
      dentin with CSMs has an adverse effect on the integrity of the dentin collagen
      matrix. However, the amount of collagen extracted was limited to the contact
      surface. Clinicians can continue to apply CSMs in endodontic procedures; however,
      caution is advised when these materials are applied to thin dentinal walls.

PMID- 22595121
TI  - Effect of ultrasonic activation on pH and calcium released by calcium hydroxide
      pastes in simulated external root resorption.
AB  - INTRODUCTION: The purpose of this study was to analyze the influence of
      ultrasonic activation of calcium hydroxide (CH) pastes on pH and calcium release
      in simulated external root resorptions. METHODS: Forty-six bovine incisors had
      their canals cleaned and instrumented, and defects were created in the external
      middle third of the roots, which were then used for the study. The teeth were
      externally made impermeable, except for the defected area, and divided into the
      following 4 groups containing 10 samples each according to the CH paste and the
      use or not of the ultrasonic activation: group 1: propylene glycol without
      ultrasonic activation, group 2: distilled water without ultrasonic activation,
      group 3: propylene glycol with ultrasonic activation, and group 4: distilled
      water with ultrasonic activation. After filling the canals with the paste, the
      teeth were restored and individually immersed into flasks with ultrapure water.
      The samples were placed into other flasks after 7, 15, and 30 days so that the
      water pH level could be measured by means of a pH meter. Calcium release was
      measured by means of an atomic absorption spectrophotometer. Six teeth were used
      as controls. The results were statistically compared using the Kruskal-Wallis and
      Mann-Whitney U tests (P < .05). RESULTS: For all periods analyzed, the pH level
      was found to be higher when the CH paste was activated with ultrasound. Calcium
      release was significantly greater (P < .05) using ultrasonic activation after 7
      and 30 days. CONCLUSIONS: The ultrasonic activation of CH pastes favored a higher
      pH level and calcium release in simulated external root resorptions.

PMID- 22595122
TI  - Comparison of the cleaning efficacy of different final irrigation techniques.
AB  - INTRODUCTION: The aim of this study was to evaluate the removal of dentin debris
      from artificially made grooves in standardized root canals by 6 different final
      irrigation techniques. METHODS: Conventional syringe irrigation, manual dynamic
      activation (MDA) with tapered or nontapered gutta-percha (GP) cones, the Safety
      Irrigator system, continuous ultrasonic irrigation (CUI), and apical negative
      pressure (ANP) irrigation were tested ex vivo in 20 root canals with a
      standardized, debris-filled groove in the apical portion of one canal wall. After
      each irrigation procedure, the groove was photographed, and the residual amount
      of dentin debris was scored. RESULTS: There was no significant difference between
      the MDA with a nontapered GP cone, the Safety Irrigator, and the ANP irrigation.
      These techniques produced better cleaning efficacy than syringe irrigation (P <
      .005) but significantly worse than the MDA with a tapered cone (P < .05). CUI was
      significantly better than all the other techniques tested in this study (P <
      .001). CONCLUSIONS: CUI was the most effective technique in dentin debris removal
      from the apical irregularities, and syringe irrigation alone was the least
      effective. MDA technique was more effective with a tapered GP cone than with a
      nontapered one.

PMID- 22595123
TI  - Evaluation of radiopacity, pH, release of calcium ions, and flow of a bioceramic
      root canal sealer.
AB  - INTRODUCTION: The aim of the present study was to evaluate the physicochemical
      properties of a bioceramic root canal sealer, Endosequence BC Sealer.
      Radiopacity, pH, release of calcium ions (Ca(2+)), and flow were analyzed, and
      the results were compared with AH Plus cement. METHODS: Radiopacity and flow were
      evaluated according to ISO 6876/2001 standards. For the radiopacity analysis,
      metallic rings with 10-mm diameter and 1-mm thickness were filled with cements.
      The radiopacity value was determined according to radiographic density (mm Al).
      The flow test was performed with 0.05 mL of cement placed on a glass plate. A 120
      g weight was carefully placed over the cement. The largest and smallest diameters
      of the disks formed were measured by using a digital caliper. The release of
      Ca(2+) and pH were measured at periods of 3, 24, 72, 168, and 240 hours with
      spectrophotometer and pH meter, respectively. Data were analyzed by analysis of
      variance and Tukey test (P < .05). RESULTS: The bioceramic endodontic cement
      showed radiopacity (3.84 mm Al) significantly lower than that of AH Plus (6.90 mm
      Al). The pH analysis showed that Endosequence BC Sealer showed pH and release of
      Ca(2+) greater than those of AH Plus (P < .05) during the experimental periods.
      The flow test revealed that BC Sealer and AH Plus presented flow of 26.96 mm and
      21.17 mm, respectively (P < .05). CONCLUSIONS: Endosequence BC Sealer showed
      radiopacity and flow according to ISO 6876/2001 recommendations. The other
      physicochemical properties analyzed demonstrated favorable values for a root
      canal sealer.

PMID- 22595124
TI  - Self-adjusting file cleaning-shaping-irrigation system optimizes the filling of
      oval-shaped canals with thermoplasticized gutta-percha.
AB  - INTRODUCTION: This study aimed to compare the filling ability of carrier-based
      thermoplasticized gutta-percha in flat-oval canals prepared using either rotary
      ProTaper files (Dentsply Maillefer, Ballaigues, Switzerland) or the Self
      Adjusting File system (SAF) (ReDent-Nova, Ra'anana, Israel). METHODS: Thirteen
      pairs of mandibular incisors were selected from a random collection. The teeth in
      each pair had single root canals with a flat-oval cross-section and similar sizes
      and dimensions. Teeth from each pair were randomly assigned to 1 of 2
      experimental groups. One group was instrumented using the ProTaper NiTi system,
      whereas the SAF system was used in the other. Root filling was performed with
      Thermafil obturators (Dentsply Tulsa Dental Products, Tulsa, OK), and teeth were
      sectioned at 6, 5, 4, and 3 mm from the apex; the cut surface was subjected to
      morphometric measurement to establish the percent gutta-percha-filled area (PGFA)
      for each section. The Wilcoxon matched-pairs signed rank test was used to assess
      the effect of the 2 preparation methods on the PGFA. RESULTS: The median PGFA in
      the ProTaper group was 77.5%, whereas the median PGFA was 90.5% in the SAF group
      (P < .05). In the SAF-instrumented group, 17.8% of the specimens had a PGFA >=95%
      compared with only 5.8% of the ProTaper-instrumented specimens (P < .05).
      CONCLUSIONS: Instrumentation of the flat-oval canals with the SAF system led to a
      significantly higher PGFA compared with ProTaper instrumentation with syringe and
      needle irrigation.

PMID- 22595125
TI  - Apically extruded debris with reciprocating single-file and full-sequence rotary
      instrumentation systems.
AB  - INTRODUCTION: The purpose of this in vitro study was to assess the amount of
      apically extruded debris using rotary and reciprocating nickel-titanium
      instrumentation systems. METHODS: Eighty human mandibular central incisors were
      randomly assigned to 4 groups (n = 20 teeth per group). The root canals were
      instrumented according to the manufacturers' instructions using the 2
      reciprocating single-file systems Reciproc (VDW, Munich, Germany) and WaveOne
      (Dentsply Maillefer, Ballaigues, Switzerland) and the 2 full-sequence rotary Mtwo
      (VDW, Munich, Germany) and ProTaper (Dentsply Maillefer, Ballaigues, Switzerland)
      instruments. Bidistilled water was used as irrigant. The apically extruded debris
      was collected in preweighted glass vials using the Myers and Montgomery method.
      After drying, the mean weight of debris was assessed with a microbalance and
      statistically analyzed using analysis of variance and the post hoc Student-Newman
      Keuls test. The time required to prepare the canals with the different
      instruments was also recorded. RESULTS: The reciprocating files produced
      significantly more debris compared with both rotary systems (P < .05). Although
      no statistically significant difference was obtained between the 2 rotary
      instruments (P > .05), the reciprocating single-file system Reciproc produced
      significantly more debris compared with all other instruments (P < .05).
      Instrumentation was significantly faster using Reciproc than with all other
      instrument (P < .05). CONCLUSIONS: Under the condition of this study, all systems
      caused apical debris extrusion. Full-sequence rotary instrumentation was
      associated with less debris extrusion compared with the use of reciprocating
      single-file systems.

PMID- 22595126
TI  - Effect of disinfection solutions on the adhesion force of root canal filling
      materials.
AB  - INTRODUCTION: Sodium hypochlorite (NaOCl) and chlorhexidine (CHX) are usually
      used to disinfect gutta-percha (GP) and Resilon (Res) cones. This study
      investigated the adhesion force (Fad) between root canal sealers and GP and Res
      cones following different disinfection protocols by using atomic force
      microscopy. METHODS: Nine flat surfaces of each material were obtained with
      medium points of GP and Res. The samples were divided into 6 groups (n = 3):
      control group GP, immersion in distilled water (DW); NaOCl group GP, immersion in
      5.25% NaOCl and then washing with DW; CHX group GP, immersion in 2% CHX and then
      washing with DW; control group Res, immersion in DW; NaOCl group Res, immersion
      in 5.25% NaOCl and then washing with DW; and CHX group Res, immersion in 2% CHX
      and then washing with DW. Atomic force microscopy tips containing AH Plus sealer
      were used to obtain force versus distance curves regarding GP surfaces. Fad was
      calculated from the force curves. The same procedure was performed with Real Seal
      SE and Res surfaces. Data were statistically analyzed. RESULTS: A higher Fad
      between solid filling materials (GP and Res) and root canal sealers was found
      when CHX solution was used. Treatment with NaOCl solution did not show influence
      on the Fad values. CONCLUSIONS: The decontamination of GP and Res with 2% CHX
      resulted in higher Fad values. The use of CHX in the disinfection process of GP
      and Res cones might be a better option before root canal obturation.

PMID- 22595127
TI  - Use of large-volume cone-beam computed tomography in identification and
      localization of horizontal root fracture in the presence and absence of
      intracanal metallic post.
AB  - INTRODUCTION: The objective of the study was to evaluate the ability of large
      volume cone-beam computed tomography (CBCT) to detect horizontal root fracture
      and to test the influence of a metallic post. METHODS: Through the examination of
      40 teeth by large-volume CBCT (20-cm height and 15-cm diameter cylinder) at 0.2
      mm voxel resolution, 2 observers analyzed the samples for the presence and
      localization of horizontal root fracture. RESULTS: The values of accuracy in the
      groups that had no metallic post ranged from 33%-68%, whereas for the samples
      with the metallic post, values showed a wide variation (38%-83%). Intraobserver
      agreement showed no statistically significant difference between the groups
      with/without metallic post; both ranged from very weak to weak (kappa, 0.09
      0.369). CONCLUSIONS: The low accuracy and low intraobserver and interobserver
      agreement reflect the difficulty in performing an adequate diagnosis of
      horizontal root fractures through a large-volume CBCT by using a small voxel
      reconstruction.

PMID- 22595128
TI  - Effect of different final irrigation solutions on dentinal tubule penetration
      depth and percentage of root canal sealer.
AB  - INTRODUCTION: The purpose of this study was to evaluate the effects of different
      solutions used for final irrigation on sealer penetration into dentinal tubules.
      METHODS: Thirty-two recently extracted human mandibular premolar teeth were
      treated with sodium hypochlorite (NaOCl) irrigation. The samples were divided
      into 4 groups according to the final irrigation solution used: (1) the EDTA
      group: 17% EDTA + 2.5% NaOCl, (2) the maleic acid (MA) group: 7% MA + 2.5% NaOCl,
      (3) the citric acid (CA) group: 10% CA + 2.5% NaOCl, and (4) the control group:
      2.5% NaOCl. All teeth were obturated using the cold lateral condensation
      technique with gutta-percha and AH 26 sealer (Dentsply; DeTrey, Konstanz,
      Germany) labeled with fluorescent dye. The teeth were sectioned at distances of
      2, 5, and 8 mm from the root apex. Total percentage and maximum depth of sealer
      penetration were measured using confocal laser scanning microscopy. RESULTS: The
      Kruskal-Wallis analysis results showed that there was a significant difference in
      the percentage and maximum depth of sealer penetration among all groups in all
      sections (P < .05).The coronal sections in each group showed a significantly
      higher percentage and maximum depth of sealer penetration than did the apical and
      middle sections (P < .05). CONCLUSIONS: Final irrigation with EDTA, MA, and CA
      after the use of NaOCl affected sealer penetration. However, there was no
      significant difference between these experimental groups (EDTA, MA, and CA) in
      all sections.

PMID- 22595129
TI  - A clinical and histological report of a tooth with an open apex treated with
      regenerative endodontics using platelet-rich plasma.
AB  - INTRODUCTION: In patients, the outcomes of teeth with necrotic pulps and open
      apexes that have been treated with regenerative endodontics have always been
      evaluated clinically and radiographically. The purpose of this case report is to
      present the clinical, radiographic, and histological findings of a regenerative
      procedure using platelet-rich plasma (PRP) 14 months after the procedure.
      METHODS: A 12-year-old boy whose maxillary second premolar tooth had been treated
      with regenerative endodontics was seen with a chief complaint of pain and
      sensitivity to cold. After clinical and radiographic examinations, a pulpal
      diagnosis of reversible pulpitis and normal periapical tissues was made for this
      tooth. Because of the patient's complaint and his guardian's insistence on either
      a root canal treatment or an extraction, a root canal treatment was performed in
      this tooth. After entry into the root canal, the soft tissue present in the canal
      was removed with the aid of a large barbed broach and examined histologically.
      RESULTS: Examination of the tissue removed from the root canal of this tooth
      revealed the presence of a vital pulp-like vital connective tissue. There was no
      evidence of bone in the specimen. Very few inflammatory cells were noted in the
      periphery of the specimen. CONCLUSIONS: Based on these findings, it appears that
      pulp-like tissue can be generated in a human tooth with the use of PRP as a
      scaffold in regenerative endodontic procedures.

PMID- 22595131
TI  - Simulation of carbon degradation in a rotary drum pilot scale composting process.
AB  - This paper studies the simulation of carbon degradation in pilot scale solid
      waste composting processes using first-order kinetic models previously calibrated
      by laboratory experiments at different temperatures. Different solid biowastes
      (olive mill waste, winery waste, sewage sludge and reed biomass) were used. Three
      mixtures were prepared from combinations of the materials listed above, and they
      were used in both the laboratory kinetic experiments and the pilot scale
      composting experiments. Lab experiments were conducted in small reactors with
      temperature (T) control and forced aeration of the solid mixture. Each biowaste
      mixture was treated at four different temperatures, 25, 40, 50 and 60  degrees C,
      with controlled moisture; the carbon (C) concentration of the samples was
      measured weekly. Two different kinetic models were used to fit the carbon
      mineralisation curves: the 2C model, which considers two organic fractions
      (biodegradable and non-biodegradable), and the 3C model, which considers three
      fractions (easily biodegradable, slowly biodegradable and non-biodegradable). In
      both cases, the kinetic rate constants were calculated by mathematical fitting.
      The influence of temperature on the rate constants was also studied for both
      models using a T-dependent equation. The theoretical k(T) curves showed classical
      shapes, and the temperatures for optimum k values and thermal inactivation were
      obtained. Once the C degradation rate constants and their T dependence equations
      were available, it was possible to simulate the evolution of C degradation in an
      actual pilot scale rotary drum composting process under varying temperatures and
      using the same biowaste mixtures. The comparison between the theoretical profiles
      and the experimental data showed that the thermophilic stage could be accurately
      simulated; however, errors and lower levels of model accuracy occurred when the
      maturation stage was simulated. The simulation was valid for all of the viewed
      biowaste mixtures. The 2C and 3C simulation profiles were quite similar in all
      cases for much of the process duration; the differences between the profiles only
      occurred after the end of the thermophilic stage. It was concluded that the 2C
      model would be only valid for shorter experimental periods, until the readily
      biodegradable carbon fraction was removed, while the 3C model reproduced the
      subsequent degradation in the maturation stage more closely.

PMID- 22595130
TI  - Oral administration of an angiotensin-converting enzyme 2 activator ameliorates
      diabetes-induced cardiac dysfunction.
AB  - We evaluated the hypothesis that activation of endogenous angiotensin-converting
      enzyme (ACE) 2 would improve cardiac dysfunction induced by diabetes. Ten days
      after diabetes induction (streptozotocin, 50 mg/kg, i.v.), male Wistar rats were
      treated with the ACE2 activator 1-[[2-(dimethylamino)ethyl]amino]-4
      (hydroxymethyl)-7-[[(4-methylphenyl)sulfonyl]oxy]-9H-xanthen-9-one (XNT, 1
      mg/kg/day, gavage) or saline (control) for 30 days. Echocardiography was
      performed to analyze the cardiac function and kinetic fluorogenic assays were
      used to determine cardiac ACE and ACE2 activities. Cardiac ACE2, ACE, Mas
      receptor, AT(1) receptor, AT(2) receptor and collagen types I and III mRNA and
      ACE2, ACE, Mas, AT(1) receptor, AT(2) receptor, ERK1/2, Akt, AMPK-alpha and AMPK
      beta(1) protein were measured by qRT-PCR and western blotting techniques,
      respectively. Histological sections of hearts were analyzed to evaluate the
      presence of hypertrophy and fibrosis. Diabetic animals presented hyperglycemia
      and diastolic dysfunction along with cardiac hypertrophy and fibrosis. XNT
      treatment prevented further increase in glycemia and improved the cardiac
      function, as well as the hypertrophy and fibrosis. These effects were associated
      with increases in cardiac ACE2/ACE ratios (activity: ~26%; mRNA: ~113%; and
      protein: ~188%) and with a decrease in AT(1) receptor expression. Additionally,
      XNT inhibited ERK1/2 phosphorylation and prevented changes in AMPK-alpha and AMPK
      beta(1) expressions. XNT treatment did not induce any significant change in AT(2)
      receptor and Akt expression. These results indicate that activation of intrinsic
      cardiac ACE2 by oral XNT treatment protects the heart against diabetes-induced
      dysfunction through mechanisms involving ACE, ACE2, ERK1/2, AMPK-alpha and AMPK
      beta(1) modulations.

PMID- 22595133
TI  - Spray dried mannitol carrier particles with tailored surface properties--the
      influence of carrier surface roughness and shape.
AB  - The aim of this work was to study the performance of mannitol carrier particles
      of tailored surface roughness in dry powder inhaler formulations. Carrier
      particles of different surface roughness were prepared by spray drying of aqueous
      mannitol solutions at different outlet temperatures at a pilot-scale spray dryer.
      However, the carrier particles did not only change in surface roughness but also
      in shape. This is why the impact of carrier shape on the performance of carrier
      based dry powder inhalates was evaluated also. The highest fine particle fraction
      (FPF), that is the amount of active pharmaceutical substance, delivered to the
      deep lung, is achieved when using rough, spherical carrier particles (FPF=29.23
      +/- 4.73%, mean arithmetic average surface roughness (mean R(a))=140.33 +/- 27.75
      nm, aspect ratio=0.925). A decrease of surface roughness (mean R(a)=88.73 +/-
      22.25 nm) leads to lower FPFs (FPF=14.62 +/- 1.18%, aspect ratio=0.918). The FPF
      further decreases when irregular shaped particles are used. For those particles,
      the micronized active accumulates within the cavities of the carrier surface
      during the preparation of the powder mixtures. Upon inhalation, the cavities may
      protect the active from being detached from the carrier.

PMID- 22595132
TI  - Intra-articular delivery of genipin cross-linked chitosan microspheres of
      flurbiprofen: preparation, characterization, in vitro and in vivo studies.
AB  - In this study, genipin cross-linked chitosan microspheres of flurbiprofen for
      intra-articular (i.a.) delivery were prepared. Emulsion-cross-linking method was
      used to prepare the microspheres using different concentrations of genipin and
      drug-to-polymer ratios. The mean particle size was found to be in the range of
      5.18-9.74 MUm with good % drug entrapment up to 80.97%. SEM indicated the
      spherical shape with smooth surface of drug-loaded cross-linked microspheres.
      FTIR confirmed cross-linking of genipin with chitosan and the absence of chemical
      interactions between drug, polymer, and cross-linker, which was further confirmed
      by TGA showing unaltered melting point of entrapped drug. DSC and XRD revealed
      the molecular dispersion of drug within microspheres. The optimized microspheres
      were able to release the drug for more than 108 h. The biocompatibility of the
      microspheres in the rat (Sprague-Dawley) knee joints was confirmed by
      histopathology. The results of pharmacokinetic study, decreased K(a) and T(max),
      lower C(max) and AUC((0-24)) and delayed MRT, suggested the significant extended
      release of flurbiprofen from microspheres in comparison with its solution at
      P<0.05. The recovery of flurbiprofen as the percent of administered dose followed
      by 24h after i.a. injection of microspheres was found to be 8.7 folds higher than
      its solution.

PMID- 22595134
TI  - Medical knowledge and the improvement of vernacular languages in the Habsburg
      Monarchy: a case study from Transylvania (1770-1830).
AB  - In all European countries, the eighteenth century was characterised by efforts to
      improve the vernaculars. The Transylvanian case study shows how both codified
      medical language and ordinary language were constructed and enriched by a large
      number of medical books and brochures. The publication of medical literature in
      Central European vernacular languages in order to popularise new medical
      knowledge was a comprehensive programme, designed on the one hand by
      intellectual, political and religious elites who urged the improvement of the
      fatherland and the promotion of the common good by perfecting the arts and
      sciences. On the other hand, the imperial administration's initiatives affected
      local forms of medical knowledge and the construction of vernacular languages. In
      the eighteenth century, the construction of vernacular languages in the Habsburg
      Monarchy took on a significant political character. However, in the process of
      building of the scientific and medical vocabulary, the main preoccupation was
      precision, clarity and accessibility of the neologisms being invented to
      encompass the medical phenomena being described. In spite of political conflicts
      among the 'nations' living in Transylvania, physicians borrowed words from
      German, Hungarian and Romanian. Thus they elevated several words used in everyday
      language to the upper social stratum of language use, leading to the invention of
      new terms to describe particular medical practices or phenomena.

PMID- 22595135
TI  - Bisphosphonate-related osteonecrosis of the jaw in patients with oral
      bisphosphonate exposure: clinical course and outcomes.
AB  - PURPOSE: To characterize the spectrum and outcomes of bisphosphonate-related
      osteonecrosis of the jaw (BRONJ) occurring with oral bisphosphonate therapy.
      MATERIALS AND METHODS: We assembled a retrospective cohort of patients who had
      developed oral BRONJ according to the 2009 American Association of Oral and
      Maxillofacial Surgeons criteria and received care within Kaiser Permanente,
      Northern California, during 2004 to 2011. Patients with intravenous
      bisphosphonate exposure were excluded. The demographic factors, comorbidities,
      pharmacologic exposure, maxillofacial findings, and outcomes were ascertained
      from the clinical and radiologic records. RESULTS: We identified 30 cases of oral
      BRONJ (median age 77 years, 87% women). All had received oral bisphosphonate for
      osteoporosis/osteopenia (median duration 4.4 years, interquartile range 1.9 to
      6.6). More than one half (57%) had comorbidities or relevant drug exposure,
      including rheumatoid arthritis, diabetes, glucocorticoid therapy, and disease
      modifying antirheumatic medications. Extractions preceded BRONJ in 17 patients
      and trauma in 3; 10 developed BRONJ spontaneously. Overall, 83% had healed within
      3 to 52 months, although the relative rate of healing varied by antecedent factor
      and/or the presence of comorbid conditions/exposures. Nearly all patients with
      trauma-related and spontaneous BRONJ healed within 1 year (median 7.0 and 7.5
      months, respectively) compared with those developing BRONJ after extraction, in
      whom the median time to healing was 18 months (P < .0001). Patients with relevant
      comorbidities had a lower probability of healing (P = .0002) and a longer median
      time to healing (20 months) than patients without comorbidities (7.5 months).
      CONCLUSIONS: We found that postextraction patients and those with comorbid
      conditions/exposures showed refractory BRONJ with prolonged healing times.
      Practitioners should be aware that the BRONJ clinical course and outcome varies
      depending on the antecedent factor and comorbidity status.

PMID- 22595136
TI  - Effectiveness of vaccination and antibiotics to control Coxiella burnetii
      shedding around calving in dairy cows.
AB  - Effectiveness of phase 1 vaccine, combined or not with tetracycline, to control
      Coxiella burnetii vaginal shedding at calving in cows was assessed through a 13
      months study in 22 Q fever clinically affected commercial dairy herds. Four
      medical strategies implemented at herd level but randomly assigned to cows
      (vaccination, vaccination and tetracycline, tetracycline, nothing) were compared.
      There was no significant interaction effect between vaccination and
      antibiotherapy. Tetracycline used once at drying off was associated with a lower
      risk of being detected shedder at calving (OR=0.40, CI 95% [0.21-0.75]), but had
      no significant effect on the bacterial load shed. Vaccination did not
      significantly prevent shedding but was significantly (OR=0.15, CI 95% [0.03
      0.85]) associated with lower bacterial load shed. Thus, vaccination using a phase
      1 vaccine and antibiotherapy using tetracycline is associated with a decrease in
      shedding in dairy cows and could contribute to reduce the bacterial load
      generated in the environment. To the best of our knowledge, this is the first
      study providing useful information for evidenced-based and rational use of
      medical strategy combining antibiotic and vaccination in infected dairy cattle
      herds.

PMID- 22595137
TI  - Potential Bacillus probiotics enhance bacterial numbers, water quality and growth
      during early development of white shrimp (Litopenaeus vannamei).
AB  - Epidemics of epizootics and occurrence of multiresistant antibiotics of
      pathogenic bacteria in aquaculture have put forward a development of effective
      probiotics for the sustainable culture. This study examined the effectiveness of
      forms of mixed Bacillus probiotics (probiotic A and probiotic B) and mode of
      probiotic administration on growth, bacterial numbers and water quality during
      rearing of white shrimp (Litopenaeus vannamei) in two separated experiments: (1)
      larval stages and (2) postlarval (PL) stages. Forms of Bacillus probiotics and
      modes of probiotic administration did not affect growth and survival of larval to
      PL shrimp. The compositions of Bacillus species in probiotic A and probiotic B
      did not affect growth and survival of larvae. However, postlarvae treated with
      probiotic B exhibited higher (P<0.05) growth than probiotic A and controls,
      indicating Bacillus probiotic composition affects the growth of PL shrimp. Total
      heterotrophic bacteria and Bacillus numbers in larval and PL shrimp or culture
      water of the treated groups were higher (P<0.05) than in controls. Levels of pH,
      ammonia and nitrite of the treated shrimp were significantly decreased, compared
      to the controls. Microencapsulated Bacillus probiotic was effective for rearing
      of PL L. vannamei. This investigation showed that administration of mixed
      Bacillus probiotics significantly improved growth and survival of PL shrimp,
      increased beneficial bacteria in shrimp and culture water and enhanced water
      quality for the levels of pH, ammonia and nitrite of culture water.

PMID- 22595138
TI  - Antibodies to West Nile virus and related flaviviruses in wild boar, red foxes
      and other mesomammals from Spain.
AB  - Red foxes (Vulpes vulpes), wild boar (Sus scrofa) and Iberian pigs (Sus scrofa
      domestica) that are raised extensively outdoors, as well as other wild
      mesomammals from south central Spain and wild boar from Donana National Park
      (DNP), were tested for antibodies against related flaviviruses by ELISA and for
      antibodies against WNV by VNT. Mean flavivirus seroprevalence according to ELISA
      was 20.4 +/- 7.8% (21 out of 103) in red foxes, 12.6 +/- 2.8% (69 out of 545) in
      wild boars, and 3.3+/-2.7% (6 out of 177) in Iberian pigs. A stone marten (Martes
      foina) also tested positive. Flavivirus seroprevalence in wild boar was
      significantly higher in DNP, and increased with age. Haemolysis of the serum
      samples limited interpretation of VNT to 28 samples, confirming WNV
      seroprevalence in one red fox, four Iberian pigs and nine wild boars. ELISA
      positive, microVNT negative samples suggest presence of non-neutralizing
      antibodies against WNV or antibodies to other antigenically related flaviviruses.
      Despite the importance of wetlands for flavivirus maintenance and amplification,
      WNV/flavivirus seroprevalence in wild boar and red foxes was not associated to
      wetland habitats. This is the first report of exposure of red foxes to WNV. With
      view to use of the tested species as sentinels for flavivirus activity, limited
      exposure of Iberian pigs that would be available for regular sampling, low
      numbers of foxes collected and concentration of wild boar harvest in the winter
      season are major drawbacks.

PMID- 22595139
TI  - Investigation of postpartum dairy cows' uterine microbial diversity using
      metagenomic pyrosequencing of the 16S rRNA gene.
AB  - The objective of this study was the use of metagenomic pyrosequencing of the 16S
      rRNA gene for the investigation of postpartum dairy cows' uterine bacterial
      diversity. The effect of subcutaneous supplementation of a trace mineral
      supplement containing Zn, Mn, Se, and Cu (Multimin North America, Inc., Fort
      Collins, CO) at 230 days of gestation and 260 days of gestation on dairy cows'
      uterine microbiota was also evaluated. Uterine lavage samples were collected at
      35 DIM and were visually scored for the presence of purulent or mucopurulent
      secretion. The same samples were also used for the acquisition of bacterial DNA.
      The 16S rRNA genes were individually amplified from each sample. Pyrosequencing
      of the samples was carried at the Cornell University Life Sciences Core
      Laboratories Center using Roche 454 GS-FLX System Titanium Chemistry. The
      Ribosomal Database Project online tools were used for the analysis of the
      obtained sequences library. Bacteroides spp., Ureaplasma spp., Fusobacterium
      spp., Peptostreptococcus spp., Sneathia spp., Prevotella spp. and Arcanobacterium
      spp. prevalence was significantly (P<0.05) higher in samples derived from cows
      that had a higher uterine lavage sample score. Bacteroides spp., Ureaplasma spp.,
      Fusobacterium spp., and Arcanobacterium spp. prevalence was significantly
      (P<0.05) higher in samples derived from cows that were not pregnant by 200 DIM.
      Anaerococcus spp., Peptostreptococcus spp., Parabacteroides spp., and
      Propionibacterium spp. prevalence was significantly (P<0.05) lower in samples
      derived from cows that were trace mineral supplemented.

PMID- 22595140
TI  - Recovery and molecular characterization of live Camelpox virus from skin 12
      months after onset of clinical signs reveals possible mechanism of virus
      persistence in herds.
AB  - Potentially pathogenic orthopoxviruses (OPVs) persist in nature and re-emerge for
      reasons we do not fully understand. New information pertaining to Orthopoxvirus
      (OPV) persistence in nature would significantly improve surveillance and control
      programs. In a recent investigation of a Camelpox virus (CMLV) outbreak in
      Eastern Saudi Arabia, atypical minute pox-like skin lesions (AMPL) persisted on
      42.9% of convalescent camels (8.8% of herd) for more than a year after the onset
      of clinical signs. In order to investigate whether AMPL were related to CMLV
      infection, AMPL homogenates were inoculated on the chorioallantoic membranes
      (CAM) of specific-pathogen-free (SPF) embryonating chicken eggs (ECE). Live CMLV
      was recovered from AMPL homogenates. The sequences of the ATIP gene of viruses
      isolated in the beginning of the outbreak, and one year later from AMPL were
      identical, and similar to the Kazakhstan isolate CMLV M-96. Virus identity was
      confirmed by sequence analysis of the CMLV A33R, A27L, B5R, and L1R orthologue
      genes. Uninfected adult camels that came in contact with animals showing AMPL
      became infected within two weeks. Since AMPL were easily missed by veterinarians
      and camel drivers, it was concluded that CMLV survival in persistent skin lesions
      may be a key mechanism in maintaining the virus in previously infected camel
      herds during inter-epizootic periods.

PMID- 22595142
TI  - Staphylococcus aureus directly activates eosinophils via platelet-activating
      factor receptor.
AB  - Colonization by SA is associated with exacerbation of AD. Eosinophilic
      inflammation is a cardinal pathological feature of AD, but little is known about
      possible direct interaction between SA and eosinophils. PAFR appears to be
      involved in phagocytosis of Gram-positive bacteria by leukocytes. The objective
      of this study was to investigate whether SA directly induces eosinophil effector
      functions via PAFR in the context of AD pathogenesis. Peripheral blood
      eosinophils were cultured with heat-killed SA, and EDN release, superoxide
      generation, and adhesion to fibronectin-coated plates were measured. Cytokines,
      released in the supernatants, were quantified by multiplex bead immunoassays.
      FISH-labeled SA was incubated with eosinophils and visualized by confocal laser
      scanning microscopy. PAFR-blocking peptide and PAFR antagonists were tested for
      inhibitory effects on SA-induced reactions. SA induced EDN release and superoxide
      generation by eosinophils in a dose-dependent manner. IL-5 significantly enhanced
      SA-induced EDN release. IL-5 and IL-17A significantly enhanced SA-induced
      superoxide generation. SA enhanced eosinophil adhesion to fibronectin, which was
      blocked by anti-CD49d, and induced eosinophil secretion of various
      cytokines/chemokines (IL-2R, IL-9, TNFR, IL-1 beta, IL-17A, IP-10, TNF-alpha,
      PDGF-bb, VEGF, and FGF-basic). After incubation of eosinophils with SA, FISH
      labeled SA was visualized in the eosinophils' cytoplasm, indicating phagocytosis.
      A PAFR-blocking peptide and two PAFR antagonists completely inhibited those
      reactions. In conclusion, SA directly induced eosinophil activation via PAFR.
      Blockade of PAFR may be a novel, therapeutic approach for AD colonized by SA.

PMID- 22595141
TI  - A novel internalization motif regulates human IFN-gamma R1 endocytosis.
AB  - This study tested the hypothesis that the IFN-gamma R1 287-YVSLI-91 intracellular
      motif regulates its endocytosis. IFN-gamma exerts its biological activities by
      interacting with a specific cell-surface RC composed of two IFN-gamma R1 and two
      IFN-gamma R2 chains. Following IFN-gamma binding and along with the initiation of
      signal transduction, the ligand and IFN-gamma R1 are internalized. Two major
      types of consensus-sorting signals are described in receptors, which are rapidly
      internalized from the plasma membrane to intracellular compartments: tyrosine
      based and dileucine-based internalization motifs. Transfection of HEK 293 cells
      and IFN-gamma R1-deficient fibroblasts with WT and site-directed, mutagenesis
      generated mutant IFN-gamma R1 expression vectors helped us to identify region IFN
      gamma R1 287-YVSLI-291 as the critical domain required for IFN-gamma-induced IFN
      gamma R1 internalization and Y287 and LI290-291 as part of a common structure
      essential for receptor endocytosis and function. This new endocytosis motif,
      YxxLI, shares characteristics of tyrosine-based and dileucine-based
      internalization motifs and is highly conserved in IFN-gamma Rs across species.
      The IFN-gamma R1 270-LI-271 dileucine motif, previously thought to be involved in
      this receptor endocytosis, showed to be unnecessary for receptor endocytosis.

PMID- 22595143
TI  - Social competence in children with epilepsy--a review.
AB  - This systematic review focuses on definitions of social competence and assessment
      methods and provides an overview of the main findings in childhood epilepsy. A
      total of 45 studies drawn from MEDLINE and PsycINFO (1998-2010) and their
      reference lists met the selection criteria. Social competence was not defined in
      the studies reviewed. The study samples varied and consisted mostly of school
      aged children. The majority of the studies focused on social adjustment and
      addressed problems in this area. Little is known about other aspects of social
      competence, namely social skills or social performance. A broader perspective on
      and definition of the assessment of social competence in children with epilepsy
      are proposed. More studies of the abilities underlying social competence, such as
      social and socio-cognitive skills, are needed in order to gain insight into the
      developmental pathways of social competence and protective factors for later
      development.

PMID- 22595144
TI  - Scientific knowledge suppresses but does not supplant earlier intuitions.
AB  - When students learn scientific theories that conflict with their earlier, naive
      theories, what happens to the earlier theories? Are they overwritten or merely
      suppressed? We investigated this question by devising and implementing a novel
      speeded-reasoning task. Adults with many years of science education verified two
      types of statements as quickly as possible: statements whose truth value was the
      same across both naive and scientific theories of a particular phenomenon (e.g.,
      "The moon revolves around the Earth") and statements involving the same
      conceptual relations but whose truth value differed across those theories (e.g.,
      "The Earth revolves around the sun"). Participants verified the latter
      significantly more slowly and less accurately than the former across 10 domains
      of knowledge (astronomy, evolution, fractions, genetics, germs, matter,
      mechanics, physiology, thermodynamics, and waves), suggesting that naive theories
      survive the acquisition of a mutually incompatible scientific theory, coexisting
      with that theory for many years to follow.

PMID- 22595145
TI  - Plant ERD2-like proteins function as endoplasmic reticulum luminal protein
      receptors and participate in programmed cell death during innate immunity.
AB  - The hypersensitive response (HR), a form of programmed cell death (PCD), is a
      tightly regulated innate immune response in plants that is hypothesized to
      restrict pathogen growth and disease development. Although considerable efforts
      have been made to understand HR PCD, it remains unknown whether the retrograde
      pathway from the Golgi to the endoplasmic reticulum (ER) is involved. Here we
      provide direct genetic evidence that two Nicotiana benthamiana homologs, ERD2a
      and ERD2b, function as ER luminal protein receptors and participate in HR PCD.
      Virus-induced gene silencing (VIGS) of ERD2a and/or ERD2b caused escape of ER
      resident proteins from the ER, and resulted in plants that were more sensitive to
      ER stress. Silencing of ERD2b delayed HR PCD induced by the non-host pathogens
      Xanthomonas oryzae pv. oryzae and Pseudomonas syringae pv. tomato DC3000.
      However, both silencing of ERD2a and co-silencing of ERD2a and ERD2b exacerbated
      HR PCD. Individual and combined suppression of ERD2a and ERD2b exaggerated R gene
      mediated cell death. Nevertheless, silencing of ERD2a and/or ERD2b had no
      detectable effects on bacterial growth. Furthermore, VIGS of several putative
      ligands of ERD2a/2b, including the ER quality control (ERQC) component genes BiP,
      CRT3 and UGGT, had different effects on HR PCD induced by different pathogens.
      This indicates that immunity-related cell death pathways are separate with
      respect to the genetic requirements for these ERQC components. These results
      suggest that ERD2a and ERD2b function as ER luminal protein receptors to ensure
      ERQC and alleviate ER stress, thus affecting HR PCD during the plant innate
      immune response.

PMID- 22595146
TI  - Macromolecular therapeutics in cancer treatment: the EPR effect and beyond.
AB  - In this review, I have discussed various issues of the cancer drug targeting
      primarily related to the EPR (enhanced permeability and retention) effect, which
      utilized nanomedicine or macromolecular drugs. The content goes back to the
      development of the first polymer-protein conjugate anticancer agent SMANCS and
      development of the arterial infusion in Lipiodol formulation into the tumor
      feeding artery (hepatic artery for hepatoma). The brief account on the EPR effect
      and its definition, factors involved, heterogeneity, and various methods of
      augmentation of the EPR effect, which showed remarkably improved clinical
      outcomes are also discussed. Various obstacles involved in drug developments and
      commercialization are also discussed through my personal experience and
      recollections.

PMID- 22595147
TI  - Disease specific biomarkers of abdominal aortic aneurysms detected by surface
      enhanced laser desorption ionization time of flight mass spectrometry.
AB  - INTRODUCTION: Biomarkers have the potential to improve the clinical management of
      patients with AAA. REPORT: A prospective, proteomics discovery study was
      undertaken to compare patients with AAA (n = 20) to matched screened controls (n
      = 19) for plasma protein expression. Surface-Enhanced-Laser-Desorption-Ionization
      Time of Flight Mass Spectrometry (SELDI ToF MS) coupled with Artificial Neural
      Networks (ANN) analysis identified six protein related diagnostic biomarker ions
      with a combined AUC of 0.89. DISCUSSION: This study discovered a signature plasma
      protein profile for patients with AAA and demonstrated that mass spectrometric
      based research for disease specific biomarker of AAA is feasible.

PMID- 22595148
TI  - An expanded series of distal bypass using the distal vein patch technique to
      improve prosthetic graft performance in critical limb ischemia.
AB  - OBJECTIVES: The endovascular first approach has led to increasing complexity for
      surgical bypass especially in those patients without autogenous conduit. The use
      of vein interposed at the distal anastomosis has been reported to improve the
      results of prosthetic grafts. This series expands our initial experience with the
      distal vein patch technique (DVP) reporting a larger cohort with enhanced follow
      up. DESIGN: A retrospective review of prospectively collected data was performed
      for distal bypasses from July 1995 to November 2008. MATERIALS/METHODS: 1296
      tibial bypasses were performed with 270 using the DVP technique. Patient
      demographics included; 49% diabetes, 20% chronic renal failure, 33% prior failed
      bypass. Indications for revascularization were claudication (9.3%), rest pain
      (27.8%), gangrene (22.2%), and non-healing ulceration (40.7%). Lack of vein for
      the bypass conduit resulted from previous failed grafts (55%), coronary bypass
      (18%), poor quality vein (23%), or prior vein stripping (8%). Follow-up ranged
      from 1 to 48 months with graft surveillance by pulse exam, ABI, and Duplex
      ultrasound. Primary patency and limb salvage +/- SE were determined by Kaplan
      Meier life-table analysis using Rutherford criteria. RESULTS: Bypasses originated
      from the external iliac (29%), CFA (55%), SFA (13%), popliteal (1%), and prior
      grafts (2%). Recipient arteries were below knee popliteal (6%), anterior tibial
      (25%), posterior tibial (30%), and peroneal (39%). Perioperative graft failure
      occurred in 13 cases with a total of 41 graft failures leading to 39 major
      amputations. Primary graft patency from one to four years was 79.8%, 75.6% 65.9%,
      and 51.2%. Corresponding limb salvage rates were 80.6%, 78.0%, 75.7%, and 67.5%.
      CONCLUSION: Although not addressed by a randomized trial, we believe this
      expanded series is a more accurate reflection of expected results confirming that
      the DVP bypass leads to reasonable long-term results for those challenging
      patients that require prosthetic distal bypass for lower extremity
      revascularization.

PMID- 22595149
TI  - Using forensic microsatellites to decipher the genetic structure of linguistic
      and geographic isolates: A survey in the eastern Italian Alps.
AB  - The study of geographically and/or linguistically isolated populations could
      represent a potential area of interaction between population and forensic
      genetics. These investigations may be useful to evaluate the suitability of loci
      which have been selected using forensic criteria for bio-anthropological studies.
      At the same time, they give us an opportunity to evaluate the efficiency of
      forensic tools for parentage testing in groups with peculiar allele frequency
      profiles. Within the frame of a long-term project concerning Italian linguistic
      isolates, we studied 15 microsatellite loci (Identifiler kit) comprising the
      CODIS panel in 11 populations from the north-eastern Italian Alps (Veneto,
      Trentino and Friuli Venezia Giulia regions). All our analyses of inter-population
      differentiation highlight the genetic distinctiveness of most Alpine populations
      comparing them either to each other or with large and non-isolated Italian
      populations. Interestingly, we brought to light some aspects of population
      genetic structure which cannot be detected using unilinear polymorphisms. In
      fact, the analysis of genotypic disequilibrium between loci detected signals of
      population substructure when all the individuals of Alpine populations are pooled
      in a single group. Furthermore, despite the relatively low number of loci
      analyzed, genetic differentiation among Alpine populations was detected at
      individual level using a Bayesian method to cluster multilocus genotypes. Among
      the various populations studied, the four linguistic minorities (Fassa Valley,
      Luserna, Sappada and Sauris) showed the most pronounced diversity and signatures
      of a peculiar genetic ancestry. Finally, we show that database replacement may
      affect estimates of probability of paternity even when the local database is
      replaced by another based on populations which share a common genetic background
      but which differ in their demographic history. These findings point to the
      importance of considering the demographic and cultural profile of populations in
      forensic applications, even in a context of substantial genetic homogeneity such
      as that of European populations.

PMID- 22595150
TI  - 1,25(OH)2D3 inhibits the deleterious effects induced by high glucose on
      osteoblasts through undercarboxylated osteocalcin and insulin signaling.
AB  - Diabetes mellitus (DM) is associated with multiple skeletal disorders, and
      vitamin D may play a functional role in the preservation of glucose tolerance.
      However, the relationship between vitamin D deficiency and DM is not well known.
      The aim of this study was to investigate the potential molecular link between
      1,25(OH)(2)D(3) regulation and glucose homeostasis. Rat primary osteoblasts were
      cultured in different conditioned medium: normal glucose, high glucose, high
      glucose and insulin, high glucose and 1,25(OH)(2)D(3), high glucose and insulin
      and 1,25(OH)(2)D(3). The activity of osteoblasts was measured by cell viability,
      alkaline phosphatase and osteocalcin assay. The potential mechanism of how
      1,25(OH)(2)D(3) affect insulin sensitivity was investigated by the assay of
      insulin receptor (IR) and vitamin D receptor (VDR) expression, and
      undercarboxylated osteocalcin (ucOC) level. The combined treatment has the
      strongest effect of inhibiting the deleterious effects induced by high glucose on
      osteoblasts, and it promoted the %ucOC value to approximately 40%, which is much
      higher than that in high glucose without treatment. Levels of IR and VDR of
      osteoblasts in combined treatment culture increased significantly compared with
      that in high glucose without treatment. So maybe 1,25(OH)(2)D(3) promotes insulin
      sensitivity of osteoblasts by activating insulin signaling and simultaneously
      stimulating ucOC secretion, which in turn regulate insulin production and
      sensitivity. 1,25(OH)(2)D(3) might be beneficial not only for diabetes, but also,
      for osteoporosis by promoting bone formation.

PMID- 22595151
TI  - Comparative fasting bioavailability of dispersible and conventional tablets of
      risperidone: a single-dose, randomized-sequence, open-label, two-period crossover
      study in healthy male Chinese volunteers.
AB  - BACKGROUND: Risperidone (RIS), an atypical antipsychotic drug, is used for the
      treatment of psychoses associated with schizophrenia and other psychiatric
      disorders in adult and pediatric populations. An oral dispersible tablet
      formulation of risperidone has been developed. This study was conducted to
      provide support for marketing authorization of this drug in China. OBJECTIVE:
      This study was designed to compare the pharmacokinetic (PK) properties and
      bioavailability of 2 RIS formulations-the dispersible formulation (test) and a
      branded formulation (reference) in healthy male Chinese volunteers. METHODS: This
      single-dose, randomized-sequence, open-label, 2-period crossover study involved
      22 healthy male Chinese volunteers. Equal numbers of eligible participants were
      randomly assigned to receive either the test drug (2 mg) or the same dose of the
      reference formulation, followed by a 2-week washout period and administration of
      the alternate formulation. The study drugs were administered after a 10-hour
      overnight fast. Blood samples were collected before dosing and at 0.33, 0.67, 1,
      1.5, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72, and 96 hours after dosing.
      Plasma concentrations of RIS and its active metabolite, 9-hydroxyrisperidone (9
      OH-RIS), were measured using LC-MS/MS. The safety profile was evaluated by
      recording adverse events (AEs), assessed using physical examination including
      vital signs, spontaneous reporting, and clinical laboratory results. The 2
      formulations were considered to have met the requirements for bioequivalence if
      the 90% CIs for the log-transformed C(max) and AUC values were within the
      predetermined ranges of 75% to 133% and 80% to 125%, respectively, according to
      the guidelines of the State Food and Drug Administration (SFDA) of China.
      RESULTS: All 22 volunteers (mean [SD] age, 22.2 [1.98] years; weight, 64.07
      [5.93] kg; height, 173 [5] cm; and body mass index, 21.2 [1.67] kg/m(2)) that
      were enrolled completed the study. For RIS, the 90% CIs for the ratios of C(max),
      AUC(0-t), and AUC(0-infinity) were 93.2% to 116.7%, 97.9% to 111.3%, and 98.0% to
      111.6%, respectively. For 9-OH-RIS, the 90% CIs were 95.8% to 113.9%, 100.2% to
      109.7%, and 100.5% to 110.3%, respectively. All values were within the
      predetermined bioequivalence range. Seven AEs were reported somnolence (4
      subjects [9.1%]) and dizziness (3 subjects [6.8%]). All AEs were transient and
      considered mild by physicians. CONCLUSIONS: The test (dispersible) and reference
      tablets met the regulatory criteria for bioequivalence as defined by the SFDA.
      Both formulations were well tolerated. Chinese Clinical Trials registration
      number: ChiCTR-TRC-12001996.

PMID- 22595152
TI  - Toxic metal (Pb, Cd and Hg) levels in the nearshore surface sediments from the
      European and Anotolian Shores of Bosphorus, Turkey.
AB  - In this study, some toxic metal such as Pb, Cd and Hg analyzes have been done in
      the nearshore surface sediments. Sediment samples have been collected from five
      parts from the European and Anotolian Shores of the Bosphorus during 2003-2004.
      Total Pb, Cd and Hg contents vary between <0.01 MUg g(-1) and 238 MUg g(-1);
      <0.01 MUg g(-1) and 0.92 MUg g(-1); 0.001 MUg g(-1) and 0.45 MUg g(-1),
      respectively. Contamination Factor (CF) values of Pb and Cd range between 1 and 3
      whilst CF values of Hg are lower than 1 in all the stations. It means that there
      are no Hg metal enrichment by natural or anthropogenic inputs contrary to
      moderately contamination for Pb and Cd metals throughout the Bosphorus sediments.

PMID- 22595153
TI  - Effect of azithromycin on systemic markers of inflammation in patients with
      cystic fibrosis uninfected with Pseudomonas aeruginosa.
AB  - BACKGROUND: While the mechanism of action by which azithromycin exerts positive
      effects inpatients with cystic fibrosis remains unclear, evidence suggests that
      azithromycin may act as an immunomodulatory agent. We examined changes in
      systemic inflammatory markers in a doubleblind, randomized, controlled trial of
      oral azithromycin in patients 6-18 years of age with cystic fibrosis who were
      uninfected with Pseudomonas aeruginosa. METHODS: WBC counts and differential,
      serum myeloperoxidase (MPO), high-sensitivity C reactive protein (hsCRP),
      intracellular adhesion molecule 1, IL-6, calprotectin, serum amyloid A (SAA),and
      granulocyte colony-stimulating factor (G-CSF) were measured at baseline and after
      28 and 168 days of treatment in patients receiving either oral azithromycin or
      placebo. RESULTS: Inflammatory markers were similar in both groups at baseline.
      HsCRP, MPO, SAA, calprotectin,and the absolute neutrophil count (ANC)
      significantly decreased from baseline today 28 in the azithromycin group compared
      with the placebo group ( P < .05). This treatment effect was sustained at day 168
      for ANC, calprotectin, and SAA ( P < .05). Changes in hsCRP, calprotectin,and SAA
      at day 28 were negatively correlated with changes in FEV 1 (L) and FEV 1(%
      predicted), as well as both absolute and relative changes in weight ( P < .05).
      Except for weight (%),the associations remained significant for calprotectin; FEV
      1 (L) and weight (%) remained significantly correlated with the 168-day change in
      hsCRP. The 168-day change in ANC was significantly correlated with changes in
      lung function, but not in weight; the change in G-CSF was significantly
      correlated with the change in weight (%) only. CONCLUSIONS: In patients not
      infected with P aeruginosa , oral azithromycin significantly reduced neutrophil
      counts and serum inflammatory markers within 28 days of initiating treatment.
      TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00431964; URL: www.clinicaltrials.gov

PMID- 22595154
TI  - Impact of aortic regurgitation after transcatheter aortic valve implantation:
      results from the REVIVAL trial.
AB  - OBJECTIVES: Understanding the severity of aortic regurgitation (AR) after
      transcatheter aortic valve implantation, its impact on left ventricular (LV)
      structure and function, and the structural factors associated with worsening AR
      could lead to improvements in patient selection, implantation technique, and
      valve design. BACKGROUND: Initial studies in patients at high risk of surgical
      aortic valve replacement have reported both central valvular and paravalvular AR
      after transcatheter aortic valve implantation. METHODS: Transthoracic
      echocardiograms were quantified from 95 patients in the REVIVAL (TRanscatheter
      EndoVascular Implantation of VALves) trial. Transthoracic echocardiograms were
      obtained before implantation of the Edwards-Sapien valve (Edwards Lifesciences,
      Irvine, California) and thereafter at selected intervals. Measurements included
      LV internal diameters and volumes, ejection fraction, aortic valve area, and the
      degree of aortic regurgitation. Measures of degree of native leaflet mobility,
      thickness, and calcification, as well as left ventricular outflow tract, aortic
      annulus, and aortic root diameters were also made. RESULTS: Eighty-four patients
      remained after 11 were excluded; 26 (29.8%) died over a period of 3 years. At 24
      h post-implantation, 75% had some degree of AR, mostly paravalvular. By 1 year,
      the mean AR grade increased slightly, but not significantly (1.1 +/- 0.8 to 1.3
      +/- 0.9), and all measures of LV structure and function improved (LV ejection
      fraction, 50.7 +/- 16.1% to 59.4 +/- 14.0%). Native aortic leaflet calcification
      and annulus diameter correlated significantly with the severity of AR at 1 year
      (p < 0.05). CONCLUSIONS: AR after transcatheter aortic valve implantation is
      frequent but is rarely more than mild. Although AR progresses, it is not
      associated with a harmful impact on LV structure and function over the first
      year. Native valve calcification and aortic annulus diameter influence the degree
      of AR at 6 months.

PMID- 22595155
TI  - Direct assessment of normal mechanical mitral valve orifice area by real-time 3D
      echocardiography.

PMID- 22595156
TI  - Image quality and radiation exposure with prospectively ECG-triggered axial
      scanning for coronary CT angiography: the multicenter, multivendor, randomized
      PROTECTION-III study.
AB  - OBJECTIVES: The purpose of this study was to evaluate image quality and radiation
      dose using a prospectively electrocardiogram (ECG)-triggered axial scan protocol
      compared with standard retrospective ECG-gated helical scanning for coronary
      computed tomography angiography. BACKGROUND: Concerns have been raised regarding
      radiation exposure during coronary computed tomography angiography. Although the
      use of prospectively ECG-triggered axial scan protocols may effectively lower
      radiation dose compared with helical scanning, it is unknown whether image
      quality is maintained in a clinical setting. METHODS: In a prospective,
      multicenter, multivendor trial, 400 patients with low and stable heart rates were
      randomized to either an axial or a helical coronary computed tomography
      angiography scan protocol. The primary endpoint was to demonstrate noninferiority
      in image quality with the axial scan protocol, which was assessed on a 4-point
      scale (1 = nondiagnostic, 4 = excellent image quality). Secondary endpoints
      included radiation dose and the rate of downstream testing during 30-day follow
      up. RESULTS: Image quality in patients scanned with the axial scan protocol
      (score 3.36 +/- 0.59) was not inferior compared with helical scan protocols (3.37
      +/- 0.59) (p for noninferiority <0.004). Axial scanning was associated with a 69%
      reduction in radiation exposure (dose-length product [estimated effective dose]
      252 +/- 147 mGy . cm [3.5 +/- 2.1 mSv] vs. 802 +/- 419 mGy . cm [11.2 +/- 5.9
      mSv] for axial vs. helical scan protocols, p < 0.001). The rate of downstream
      testing did not differ (13.8% vs. 15.9% for axial vs. helical scan protocols, p =
      0.555). CONCLUSIONS: In patients with stable and low heart rates, the
      prospectively ECG-triggered axial scan protocol maintained image quality but
      reduced radiation exposure by 69% compared with helical scanning. Axial computed
      tomography data acquisition should be strongly recommended in suitable patients
      to avoid unnecessarily high radiation exposure.

PMID- 22595157
TI  - CMR imaging assessing viability in patients with chronic ventricular dysfunction
      due to coronary artery disease: a meta-analysis of prospective trials.
AB  - OBJECTIVES: The purpose of this study was to compare the diagnostic accuracy of
      cardiac magnetic resonance (CMR) assessing myocardial viability in patients with
      chronic left ventricular (LV) dysfunction due to coronary artery disease using 3
      techniques: 1) end-diastolic wall thickness (EDWT); 2) low-dose dobutamine (LDD);
      and 3) contrast delayed enhancement (DE). BACKGROUND: CMR has been proposed to
      assess myocardial viability over the past decade. However, the best CMR strategy
      to evaluate patients being contemplated for revascularization has not yet been
      determined. Some centers advocate DE CMR due to its high sensitivity to identify
      scar, whereas others favor the use of LDD CMR for its ability to identify
      contractile reserve. METHODS: A systematic review of MEDLINE, Cochrane, and
      Embase for all the prospective trials assessing myocardial viability in subjects
      with chronic LV dysfunction using CMR was performed using a standard approach for
      meta-analysis for diagnostic tests and a bivariate analysis of sensitivity,
      specificity, positive predictive value (PPV), and negative predictive value
      (NPV). RESULTS: A total of 24 studies of CMR evaluating myocardial viability with
      698 patients fulfilled the inclusion criteria. Eleven studies used DE, 9 studies
      used LDD, and 4 studies used EDWT. Our meta-analysis indicates that among CMR
      methods, DE CMR provides the highest sensitivity as well as the highest NPV (95%
      and 90%, respectively) for predicting improved segmental LV contractile function
      after revascularization, followed by EDWT CMR, whereas LDD CMR demonstrated the
      lowest sensitivity/NPV among all modalities. On the other hand, LDD CMR offered
      the highest specificity and PPV (91% and 93%, respectively), followed by DE CMR,
      whereas EDWT showed the lowest of these parameters. CONCLUSIONS: DE CMR provides
      the highest sensitivity and NPV, whereas LDD CMR provides the best specificity
      and PPV. In light of these findings, integrating these 2 methods should provide
      increased accuracy in evaluating patients with chronic LV dysfunction being
      considered for revascularization.

PMID- 22595158
TI  - Myocardial viability: dead or alive is not the question!

PMID- 22595159
TI  - Diagnostic performance of CMR imaging compared with EMB in patients with
      suspected myocarditis.
AB  - OBJECTIVES: The goal of this study was to assess the diagnostic performance of
      cardiac magnetic resonance (CMR) compared with endomyocardial biopsy in patients
      with suspected acute myocarditis (AMC) and chronic myocarditis (CMC). BACKGROUND:
      Several studies have reported an encouraging diagnostic performance of CMR in
      myocarditis. However, the comparison of CMR with clinical data only and the use
      of preselected patient populations are important limitations of the majority of
      these reports. METHODS: One hundred thirty-two consecutive patients with
      suspected AMC (defined by symptoms <= 14 days; n = 70) and CMC (defined by
      symptoms >14 days; n = 62) were included. Patients underwent cardiac
      catheterization with left ventricular endomyocardial biopsy and CMR, including
      T(2)-weighted imaging for assessment of edema, T(1)-weighted imaging before and
      after contrast administration for evaluation of hyperemia, and assessment of late
      gadolinium enhancement. CMR results were considered to be consistent with the
      diagnosis of myocarditis if 2 of 3 CMR techniques were positive. RESULTS: Within
      the total population, myocarditis was the most common diagnosis on endomyocardial
      biopsy analysis (62.9%). Viral genomes were detected in 30.3% (40 of 132) of
      patients within the total patient population and significantly more often in
      patients with AMC than CMC (40.0% vs. 19.4%; p = 0.013). For the overall cohort
      of patients with either suspected AMC or CMC, the diagnostic sensitivity,
      specificity, and accuracy of CMR were 76%, 54%, and 68%, respectively. The best
      diagnostic performance was observed in patients with suspected AMC (sensitivity,
      81%; specificity, 71%; and accuracy, 79%). In contrast, diagnostic performance of
      CMR in suspected CMC was found to be unsatisfactory (sensitivity, 63%;
      specificity, 40%; and accuracy, 52%). CONCLUSIONS: The results of this study
      underline the usefulness of CMR in patients with suspected AMC. In contrast, the
      diagnostic performance of CMR in patients with suspected CMC might not be
      sufficient to guide clinical management.

PMID- 22595160
TI  - CMR in myocarditis: valuable tool, room for improvement.

PMID- 22595162
TI  - Imaging vascular nicotine receptors: a new window onto vascular disease.

PMID- 22595161
TI  - Feasibility of [18F]-2-Fluoro-A85380-PET imaging of human vascular nicotinic
      acetylcholine receptors in vivo.
AB  - OBJECTIVES: The aim of this feasibility study was to evaluate [(18)F]-2-Fluoro
      A85380 for in vivo imaging of arterial nicotinic acetylcholine receptors (nAChRs)
      in humans. Furthermore, potentially different vascular uptake patterns of this
      new tracer were evaluated in healthy volunteers and in patients with
      neurodegenerative disorders. BACKGROUND: [(18)F]-2-Fluoro-A85380 was developed
      for in vivo positron emission tomography (PET) imaging of nAChR subunits in the
      human brain. These nAChRs are also found in arteries and seem to mediate the
      deleterious effects of nicotine as a part of tobacco smoke in the vasculature. It
      has been previously shown that uptake patterns of the radiotracer in the brain
      differs in patients with neurodegenerative disorders compared with healthy
      controls. METHODS: [(18)F]-2-Fluoro-A85380 uptake was quantified in the ascending
      and descending aorta, the aortic arch, and the carotids in 5 healthy volunteers
      and in 6 patients with either Parkinson's disease or multiple system atrophy,
      respectively, as the maximum target-to-background ratio. The maximal standardized
      uptake value values, the single hottest segment, and the percent active segments
      of the [(18)F]-2-Fluoro-A85380 uptake in the arteries were also assessed.
      RESULTS: [(18)F]-2-Fluoro-A85380 uptake was clearly visualized and maximum target
      to-background ratio uptake values corrected for the background activity of the
      tracer showed specific tracer uptake in the arterial walls. Significantly higher
      uptake values were found in the descending aorta. Comparison between volunteers
      and patients revealed significant differences, with lower [(18)F]-2-Fluoro-A85380
      uptake in the patient group when comparing single arterial territories but not
      when all arterial territories were pooled together. CONCLUSIONS: [(18)F]-2-Fluoro
      A85380 can provide specific information on the nAChR distribution in human
      arteries. Vascular nAChR density seems to be lower in patients with Parkinson's
      disease or multiple system atrophy. Once confirmed in larger study populations
      and in the experimental setting, this approach might provide insights into the
      pathogenic role of nAChRs in the human vasculature.

PMID- 22595164
TI  - Is viability imaging still relevant in 2012?

PMID- 22595163
TI  - High platelet reactivity on clopidogrel therapy correlates with increased
      coronary atherosclerosis and calcification: a volumetric intravascular ultrasound
      study.
AB  - OBJECTIVES: This study sought to evaluate the relationship between platelet
      reactivity and atherosclerotic burden in patients undergoing percutaneous
      coronary intervention (PCI) with pre-intervention volumetric intravascular
      ultrasound (IVUS) imaging. BACKGROUND: Atherosclerosis progresses by the
      pathologic sequence of subclinical plaque rupture, thrombosis, and healing. In
      this setting, increased platelet reactivity may lead to more extensive arterial
      thrombosis at the time of plaque rupture, leading to a more rapid progression of
      the disease. Alternatively, abnormal vessel wall biology with advanced
      atherosclerosis is known to enhance platelet reactivity. Therefore, it is
      possible that by either mechanism, increased platelet reactivity may be
      associated with greater atherosclerotic burden. METHODS: This study included
      patients who underwent PCI with pre-intervention IVUS imaging and platelet
      reactivity functional assay (P2Y(12) reaction units) performed >16 h after PCI,
      after the stabilization of clopidogrel therapy (administered before PCI).
      Platelet reactivity >230 P2Y(12) reaction units defined high on-treatment
      platelet reactivity (HPR). RESULTS: Among 335 patients (mean age 65.0 years, 71%
      men), there were 109 patients with HPR (32.5%) and 226 without HPR (67.5%), with
      HPR being associated with diabetes and chronic renal insufficiency. By IVUS
      analysis, patients with HPR had significantly greater target lesion calcium
      lengths, calcium arcs, and calcium indexes. Furthermore, patients with HPR tended
      to have longer lesions and greater volumetric dimensions, indicating higher
      plaque volume, larger total vessel volume, and also greater luminal volume,
      despite similar plaque burden. By multivariate analysis controlling for baseline
      clinical variables, HPR was the single consistent predictor of all IVUS
      parameters examined, including plaque volume, calcium length, and calcium arc.
      CONCLUSIONS: Increased platelet reactivity on clopidogrel treatment, defined as
      >230 P2Y(12) reaction units, is associated with greater coronary artery
      atherosclerotic disease burden and plaque calcification.

PMID- 22595166
TI  - Multiplanar visualization of blood flow using echocardiographic particle imaging
      velocimetry.

PMID- 22595165
TI  - Cell tracking and the development of cell-based therapies: a view from the
      Cardiovascular Cell Therapy Research Network.
AB  - Cell-based therapies are being developed for myocardial infarction (MI) and its
      consequences (e.g., heart failure) as well as refractory angina and critical limb
      ischemia. The promising results obtained in preclinical studies led to the
      translation of this strategy to clinical studies. To date, the initial results
      have been mixed: some studies showed benefit, whereas in others, no benefit was
      observed. There is a growing consensus among the scientific community that a
      better understanding of the fate of transplanted cells (e.g., cell homing and
      viability over time) will be critical for the long-term success of these
      strategies and that future studies should include an assessment of cell homing,
      engraftment, and fate as an integral part of the trial design. In this review,
      different imaging methods and technologies are discussed within the framework of
      the physiological answers that the imaging strategies can provide, with a special
      focus on the inherent regulatory issues.

PMID- 22595167
TI  - Platypnea-orthodeoxia syndrome due to PFO and aortic dilation.

PMID- 22595168
TI  - Superior doctor at a point-of-care: a call to change HF management.

PMID- 22595170
TI  - Viability is in the eye of the beholder...

PMID- 22595171
TI  - Reference citations in iJACC: litera scripta manet.

PMID- 22595172
TI  - Effects of skin-to-skin contact on autonomic pain responses in preterm infants.
AB  - The purpose of this randomized crossover trial was to determine the effects on
      autonomic responses in preterm infants of longer Kangaroo Care (30 minutes, KC30)
      and shorter KC (15 minutes, KC15) before and throughout heel stick compared with
      incubator care (IC). Beat-to-beat heart rate (HR) and spectral power analysis of
      heart rate variability, low frequency power (LF), high frequency power (HF), and
      LF/HF ratio were measured in 26 infants. HR changes from Baseline to Heel Stick
      were significantly less in KC30 and KC15 than in IC, and more infants had HR
      decrease in IC than in 2 KC conditions. In IC, LF and HF significantly increased
      from Baseline to Heel Stick and dropped from Heel Stick to Recovery; in 2 KC
      conditions, no changes across study phases were found. During Heel Stick, LF and
      HF were significantly higher in IC than in KC30. In all 3 conditions, LF/HF ratio
      decreased from Baseline to Heel Stick and increased to Recovery; no differences
      were found between IC and two KC conditions. Both longer and shorter KC before
      and throughout heel stick can stabilize HR response in preterm infants, and
      longer KC significantly affected infants' sympathetic and parasympathetic
      responses during heel stick compared with incubator care. PERSPECTIVE: This study
      showed that KC has a significant effect on reducing autonomic pain responses in
      preterm infants. The findings support that KC is a safe and effective pain
      intervention in the neonatal intensive care unit.

PMID- 22595173
TI  - The discovery and development of selective 3-fluoro-4-aryloxyallylamine
      inhibitors of the amine oxidase activity of semicarbazide-sensitive amine
      oxidase/vascular adhesion protein-1 (SSAO/VAP-1).
AB  - A new class of 3-fluoroallyl amine-based SSAO/VAP-1 inhibitors is reported. These
      compounds have excellent selectivity over diamine oxidase, MAO-A and MAO-B.
      Synthesis and SAR studies leading to compound 28 (PXS-4159A) are reported. The
      pharmacokinetic profile of 28 in the rat, together with activity in a murine
      model of lung inflammation are also disclosed.

PMID- 22595174
TI  - Pre-steady state kinetic analysis of cyclobutyl derivatives of 2'-deoxyadenosine
      5'-triphosphate as inhibitors of HIV-1 reverse transcriptase.
AB  - Pre-steady state kinetic analysis was utilized for biochemical evaluation of a
      series of cyclobutyl adenosine nucleotide analogs with HIV-1 RT(WT). The
      phosphonyl-diphosphate form of the cyclobutyl nucleotide, 5, was the most
      efficiently incorporated of the series. Nucleotide 5 was fourfold more
      efficiently incorporated than the FDA approved TFV-DP by RT(WT). The kinetics of
      incorporation for 5 using the drug resistant mutant enzyme K65R was also
      determined. Compound 5 was threefold more efficiently incorporated compared to
      TFV-DP with RT(K65R). These results demonstrate cyclobutyl adenosine analogs can
      act as substrates for incorporation by HIV-1 RT and be a potential scaffold for
      HIV inhibitors.

PMID- 22595175
TI  - N-Acyl and N-sulfonyloxazolidine-2,4-diones are pseudo-irreversible inhibitors of
      serine proteases.
AB  - The synthesis, inhibitory activity and mode of action of oxazolidine-2,4-diones
      against porcine pancreatic elastase, here used as a model for human neutrophil
      elastase, are reported. The nature of N-substitution at the oxazolidine-2,4-dione
      scaffold has large effect on the inhibitory potency against elastase. N-Acyl and
      N-sulfonyloxazolidine-2,4-diones emerged as potent pseudo-irreversible
      inhibitors, displaying high second-order rate constants for PPE inactivation. The
      title compounds were also shown to be potent inhibitors of human neutrophil
      elastase (HNE) and proteinase-3, and weak inhibitors of human cathepsin G. The
      results herein presented show that the oxazolidine-2,4-diones represent a new
      promising class of serine protease inhibitors.

PMID- 22595176
TI  - Discovery and optimization of a potent and selective triazolopyridinone series of
      c-Met inhibitors.
AB  - Deregulation of the receptor tyrosine kinase c-Met has been implicated in several
      human cancers and is an attractive target for small molecule drug discovery.
      Herein, we report the discovery of a structurally diverse series of carbon-linked
      quinoline triazolopyridinones, which demonstrates nanomolar inhibition of c-Met
      kinase activity. This novel series of inhibitors exhibits favorable
      pharmacokinetics as well as potent inhibition of HGF-mediated c-Met
      phosphorylation in a mouse liver pharmacodynamic model.

PMID- 22595177
TI  - Discovery of novel EGFR tyrosine kinase inhibitors by structure-based virtual
      screening.
AB  - By using of structure-based virtual screening, 13 novel epidermal growth factor
      receptor (EGFR) tyrosine kinase inhibitors were discovered from 197,116 compounds
      in the SPECS database here. Among them, 8 compounds significantly inhibited EGFR
      kinase activity with IC(50) values lower than 10 MUM. 3-{[1-(3-Chloro-4
      fluorophenyl)-3,5-dioxo-4-pyrazolidinylidene]methyl}phenyl 2-thiophenecarboxylate
      (13), particularly, was the most potent inhibitor possessing the IC(50) value of
      3.5 MUM. The docking studies also provide some useful information that the
      docking models of the 13 compounds are beneficial to find a new path for
      designing novel EGFR inhibitors.

PMID- 22595178
TI  - Investigation of the nucleotide triphosphate substrate specificity of Homo
      sapiens UDP-N-acetylgalactosamine pyrophosphorylase (AGX1).
AB  - Nucleotide sugars are essential glycosyl donors for Leloir-type
      glycosyltransferases. The UDP-N-acetylgalactosamine pyrophosphorylase (UDP-GalNAc
      PP; AGX1) from Homo sapiens catalyzes the synthesis of UDP-N-acetylgalactosamine
      from N-acetylgalactosamine 1-phosphate and UTP. In this Letter, we systematically
      studied nucleotide substrate specificity of AGX1 during its uridyltransfer
      reaction, and described the capability of AGX1 to catalyze dUTP and dTTP to their
      corresponding nucleotide sugars for the first time. Furthermore, using such a
      eukaryotic enzyme, we synthesized dUDP-GalNAc and dTDP-GalNAc in multiple mg
      scale in vitro efficiently and rapidly.

PMID- 22595179
TI  - Design and synthesis of gambogic acid analogs as potent cytotoxic and anti
      inflammatory agents.
AB  - Prenyl- and pyrano-xanthones derived from 1,3,6-trihydroxy-9H-xanthen-9-one, a
      basic backbone of gambogic acid (GA), were synthesized and evaluated for in vitro
      cytotoxic effects against four human cancer cell lines (KB, KBvin, A549, and DU
      145) and anti-inflammatory activity toward superoxide anion generation and
      elastase release by human neutrophils in response to fMLP/CB. Among them,
      prenylxanthones 7-13 were generally less active than pyranoxanthones 14-21 in
      both anticancer and anti-inflammatory assays. Furthermore, two angular 3,3
      dimethypyranoxanthones (16 and 20) showed the greatest and selective activity
      against the KBvin multidrug resistant (MDR) cell line with IC(50) values of 0.9
      and 0.8 MUg/mL, respectively. An angular 3-methyl-3-prenylpyranoxanthone (17)
      selectively inhibited elastase release with 200 times more potency than
      phenylmethylsulfonyl fluoride (PMSF), the positive control.

PMID- 22595180
TI  - Validity of a short-term quality of life questionnaire in patients undergoing
      joint replacement: the Quality of Recovery-40.
AB  - One hundred thirty-two patients undergoing total hip or knee arthroplasty were
      evaluated before and after surgery with the Quality of Recovery-40 (QoR-40) and
      the Short Form 12 (SF-12) questionnaires seven times over a 4-month period, with
      the objective of comparing their psychometric properties. Physical dimensions of
      the QoR-40 and SF-12 were not related in the days after surgery but moderately
      related over the first month. Only the change in score for the physical
      independence dimension of the QoR-40 exceeded measurement error. Effect sizes
      were larger for the QoR-40 within the first month post-surgery and larger for the
      SF-12 past 1 month. Effect sizes were larger for the physical dimensions of both
      instruments compared to the psychological dimensions. Only the physical
      independence dimension of the QoR-40 appears useful to assess the quality of life
      in the first month following surgery.

PMID- 22595181
TI  - Biomechanical analysis of acetabular revision constructs: is pelvic discontinuity
      best treated with bicolumnar or traditional unicolumnar fixation?
AB  - Pelvic discontinuity in revision total hip arthroplasty presents problems with
      component fixation and union. A construct was proposed based on bicolumnar
      fixation for transverse acetabular fractures. Each of 3 reconstructions was
      performed on 6 composite hemipelvises: (1) a cup-cage construct, (2) a posterior
      column plate construct, and (3) a bicolumnar construct (no. 2 plus an antegrade
      4.5-mm anterior column screw). Bone-cup interface motions were measured, whereas
      cyclical loads were applied in both walking and descending stair simulations. The
      bicolumnar construct provided the most stable construct. Descending stair mode
      yielded more significant differences between constructs. The bicolumnar construct
      provided improved component stability. Placing an antegrade anterior column screw
      through a posterior approach is a novel method of providing anterior column
      support in this setting.

PMID- 22595182
TI  - The importance of bony impingement in restricting flexion after total knee
      arthroplasty: computer simulation model with clinical correlation.
AB  - We constructed patient-specific models from computed tomography data after total
      knee arthroplasty to predict knee flexion based on implant-bone impingement. The
      maximum flexion before impingement between the femur and the tibial insert was
      computed using a musculoskeletal modeling program (KneeSIM; LifeModeler, Inc, San
      Clemente, California) during a weight-bearing deep knee bend. Postoperative
      flexion was measured in a clinical cohort of 21 knees (low-flex group: 6 knees
      with <100 degrees  of flexion and high-flex group: 15 size-matched knees with
      >125 degrees  of flexion at 2 years). Average predicted flexion angles were
      within 2 degrees  of clinical measurements for the high-flex group. In the low
      flex group, 4 cases had impingement involving the bone cut at the posterior
      condyle, and the average predicted knee flexion was 102 degrees  compared with 93
      degrees  measured clinically. These results indicate that the level of the distal
      femoral resection should be carefully planned and that exposed bone proximal to
      the tips of the posterior condyles of the femoral component should be removed if
      there is risk of impingement.

PMID- 22595183
TI  - Hip resurfacing with the Biomet Hybrid ReCap-Magnum system: 7-year results.
AB  - The purpose of this study was to report our clinical outcome of a large series of
      metal-on-metal hip resurfacing arthroplasty (HRA) using the hybrid Biomet ReCap
      Magnum system. This is a single-designer surgeon series with an average of 5 +/-
      1 years. Seven hundred forty consecutive hybrid HRAs were performed in 653
      patients. Kaplan-Meier survivorship with any revision as an end point was 96.4%
      at 7 years. Twenty-five (3.4%) cases were revised: 8 due to acetabular component
      loosening, 6 due to femoral neck facture, 4 due to failure of femoral component
      fixation, 2 due to deep infection, 2 due to adverse wear, 1 due to psoas
      tendonitis, 1 due to recurrent dislocation, and 1 due to unexplained pain. Biomet
      ReCap and Magnum HRA components with hybrid fixation methods showed excellent
      survivorship for a minimally selected young patient cohort at 7 years.

PMID- 22595184
TI  - A blue native polyacrylamide gel electrophoretic technology to probe the
      functional proteomics mediating nitrogen homeostasis in Pseudomonas fluorescens.
AB  - As glutamate and ammonia play a pivotal role in nitrogen homeostasis, their
      production is mediated by various enzymes that are widespread in living
      organisms. Here, we report on an effective electrophoretic method to monitor
      these enzymes. The in gel activity visualization is based on the interaction of
      the products, glutamate and ammonia, with glutamate dehydrogenase (GDH, EC:
      1.4.1.2) in the presence of either phenazine methosulfate (PMS) or 2,6
      dichloroindophenol (DCIP) and iodonitrotetrazolium (INT). The intensity of the
      activity bands was dependent on the amount of proteins loaded, the incubation
      time and the concentration of the respective substrates. The following enzymes
      were readily identified: glutaminase (EC: 3.5.1.2), alanine transaminase (EC:
      2.6.1.2), aspartate transaminase (EC: 2.6.1.1), glycine transaminase (EC:
      2.6.1.4), ornithine oxoacid aminotransferase (EC: 2.6.1.13), and carbamoyl
      phosphate synthase I (EC: 6.3.4.16). The specificity of the activity band was
      confirmed by high pressure liquid chromatography (HPLC) following incubation of
      the excised band with the corresponding substrates. These bands are amenable to
      further molecular characterization by a variety of analytical methods. This
      electrophoretic technology provides a powerful tool to screen these enzymes that
      contribute to nitrogen homeostasis in Pseudomonas fluorescens and possibly in
      other microbial systems.

PMID- 22595185
TI  - Management of inflammatory bowel disease in pregnancy.
AB  - BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is a chronic disease
      affecting mainly young people in their reproductive years. IBD therefore has a
      major impact on patients' family planning decisions. Management of IBD in
      pregnancy requires a challenging balance between optimal disease control and drug
      safety considerations. This article aims to provide a framework for clinical
      decision making in IBD based on review of the literature on pregnancy-related
      topics. METHODS: Medline searches with search terms 'IBD', 'Crohn's disease' or
      'ulcerative colitis' in combination with keywords for the topics fertility,
      pregnancy, congenital abnormalities and drugs names of drugs used for treatment
      of IBD. RESULTS: IBD patients have normal fertility, except for women after ileal
      pouch-anal anastomosis (IPAA) and men under sulfasalazine treatment. Achieving
      and maintaining disease remission is a key factor for successful pregnancy
      outcomes in this population, as active disease at conception carries an increased
      risk of preterm delivery and low birth weight. Clinicians should discuss the need
      for drug therapy to maintain remission with their patients in order to ensure
      therapy compliance. Most IBD drugs are compatible with pregnancy, except for
      methotrexate and thalidomide. If possible, anti-TNF therapy should be stopped by
      the end of the second trimester and the choice of delivery route should be
      discussed with the patient. CONCLUSIONS: Disease control prior to conception and
      throughout pregnancy is the cornerstone of successful pregnancy management in IBD
      patients.

PMID- 22595187
TI  - The interactive role of distress tolerance and borderline personality disorder in
      suicide attempts among substance users in residential treatment.
AB  - The primary purpose of this study was to examine the interactive effect of
      borderline personality disorder (BPD) and distress tolerance (DT) on suicidal
      behavior across levels of intent to die (clear vs ambiguous) and medical
      severity. One hundred seventy-six adult patients in residential substance use
      disorder treatment were administered a series of structured interviews,
      behavioral assessments, and self-report questionnaires. A series of analyses of
      covariance and multiple regression analyses were conducted to test hypotheses
      using both categorical and dimensional measures of BPD and DT. Analyses supported
      hypotheses, indicating that patients with BPD who exhibit high DT are at the
      greatest risk for engaging in chronic and medically serious suicidal behavior.
      Although high DT is unlikely to be inherently problematic, results suggest that
      within the context of severe psychopathology (eg, co-occurring BPD-substance use
      disorder), the ability to withstand aversive internal states in pursuit of a goal
      (eg, one's own death) may enable individuals to persist in otherwise
      unsustainable behavior. In this sense, DT may function in a manner consistent
      with the acquired capability for suicide (a component of the interpersonal
      psychological theory of suicidal behavior defined by a diminished fear of death
      and enhanced tolerance for pain that, in the presence of suicidal desire, enables
      individuals to enact lethal self-injury).

PMID- 22595188
TI  - Physical growth and cognitive abilities in concordant versus discordant birth
      weight twins at three years old.
AB  - BACKGROUND: Discordant birth weight twins have been shown to have high rates of
      adverse perinatal outcomes, but little is known about their growth and
      development. AIM: To determine whether smaller and larger birth weight premature
      twins in concordant and discordant birth weight groups differ on measures of
      physical growth and intelligence at 3 years. STUDY DESIGN: Prospective cohort
      study. Eight-four children, 52 concordant and 32 discordant birth weight twin
      pairs, were measured for height, weight, and head circumference and on
      intelligence at 3 years. Perinatal and demographic variables, including birth
      weight, head circumference, small for gestational age, zygosity, in vitro
      fertilization, gender and social class were recorded. RESULTS: Smaller and larger
      birth weight twins did not differ significantly from each other on any growth
      parameters in either concordant or discordant birth weight groups at 3 years of
      age. Smaller birth weight twins in the discordant birth weight group performed
      significantly less well on Verbal, Performance, and Full Scale IQ scores (Verbal
      IQ for smaller twins was 8.6 points lower, p<0.005; Performance IQ, 11.9 points
      lower, p<0.03; Full Scale IQ, 12.4 points lower, p<0.004), but there were no
      significant intra-twin differences between larger and smaller birth weight
      concordant twins. CONCLUSIONS: Smaller discordant birth weight twins performed
      significantly less well on intelligence, although they did not differ
      significantly from their larger twins on growth parameters at 3 years old. We
      conclude that smaller discordant birth weight twins had less optimal intra
      uterine environments than their larger birth weight twin, which affected both
      their birth weights and brain development.

PMID- 22595189
TI  - ClpP: a structurally dynamic protease regulated by AAA+ proteins.
AB  - Proteolysis is an important process for many aspects of bacterial physiology. Clp
      proteases carry out a large proportion of protein degradation in bacteria. These
      enzymes assemble in complexes that combine the protease ClpP and the unfoldase,
      ClpA or ClpX. ClpP oligomerizes as two stacked heptameric rings enclosing a
      central chamber containing the proteolytic sites. ClpX and ClpA assemble into
      hexameric rings that bind both axial surfaces of the ClpP tetradecamer forming a
      barrel-like complex. ClpP requires association with ClpA or ClpX to unfold and
      thread protein substrates through the axial pore into the inner chamber where
      degradation occurs. A gating mechanism regulated by the ATPase exists at the
      entry of the ClpP axial pore and involves the N-terminal regions of the ClpP
      protomers. These gating motifs are located at the axial regions of the
      tetradecamer but in most crystal structures they are not visible. We also lack
      structural information about the ClpAP or ClpXP complexes. Therefore, the
      structural details of how the axial gate in ClpP is regulated by the ATPases are
      unknown. Here, we review our current understanding of the conformational changes
      that ClpA or ClpX induce in ClpP to open the axial gate and increase substrate
      accessibility into the degradation chamber. Most of this knowledge comes from the
      recent crystal structures of ClpP in complex with acyldepsipeptides (ADEP)
      antibiotics. These small molecules are providing new insights into the gating
      mechanism of this protease because they imitate the interaction of ClpA/ClpX with
      ClpP and activate its protease activity.

PMID- 22595190
TI  - Coronary calcium score, albuminuria and inflammatory markers in type 2 diabetic
      patients: associations and prognostic implications.
AB  - AIMS: To investigate the relationship of coronary artery calcium (CAC) scores
      with common carotid artery intima media thickness (CCA-IMT), albuminuria and
      inflammatory factors in type 2 diabetes. METHODS AND RESULTS: 128 asymptomatic
      type 2 diabetic patients, with at least one cardiovascular risk factor in
      addition to diabetes, were included in the study. CAC scores, carotid arteries
      plaque formation and CCA-IMT were assessed. The patients were followed for a mean
      period of 36.6 +/- 3.3 months. Linear regression analysis identified the
      logarithmically transformed (Ln) albuminuria (beta=0.32, P=0.007), age
      (beta=0.04, P=0.001) and the uric acid (beta=0.13, P=0.04) as independent
      determinants of the CAC score. During follow-up period, cardiovascular events
      occurred in 18 out of 46 patients with CAC score >=100 compared with 5 out of 82
      patients with CAC score <100 (log rank, P<0.0001). Multivariate Cox proportional
      hazards analysis identified LnCAC score (P<0.0001), LnAlbuminuria (P=0.01) and
      uric acid (P=0.03) as independent predictors for cardiovascular events.
      CONCLUSIONS: There was a significant relationship between CAC score, albuminuria
      and inflammation in patients with type 2 diabetes. LnCAC score together with
      LnAlbuminuria and uric acid were identified as independent predictors of
      cardiovascular events in these patients.

PMID- 22595191
TI  - Total diet study on pesticide residues in France: levels in food as consumed and
      chronic dietary risk to consumers.
AB  - Chronic dietary exposure to pesticide residues was assessed for the French
      population using a total diet study (TDS) to take into account realistic levels
      in foods as consumed at home (table-ready). Three hundred and twenty-five
      pesticides and their transformation products, grouped into 283 pesticides
      according to their residue definition, were sought in 1235 composite samples
      corresponding to 194 individual food items that cover 90% of the adult and child
      diet. To make up the composite samples, about 19,000 food products were bought
      during different seasons from 2007 to 2009 in 36 French cities and prepared
      according to the food preparation practices recorded in the individual and
      national consumption survey (INCA2). The results showed that 37% of the samples
      contained one or more residues. Seventy-three pesticides were detected and 55
      quantified at levels ranging from 0.003 to 8.7mg/kg. The most frequently detected
      pesticides, identified as monitoring priorities in 2006, were the post-harvest
      insecticides pirimiphos-methyl and chlorpyrifos-methyl-particularly in wheat
      based products-together with chlorpyrifos, iprodione, carbendazim and imazalil,
      mainly in fruit and fruit juices. Dietary intakes were estimated for each subject
      of INCA2 survey, under two contamination scenarios to handle left-censored data:
      lower-bound scenario (LB) where undetected results were set to zero, and upper
      bound (UB) scenario where undetected results were set to the detection limit. For
      90% of the pesticides, exposure levels were below the acceptable daily intake
      (ADI) under the two scenarios. Under the LB scenario, which tends to
      underestimate exposure levels, only dimethoate intakes exceeded the ADI for high
      level consumers of cherry (0.6% of children and 0.4% of adults). This pesticide,
      authorised in Europe, and its metabolite were detected in both cherries and
      endives. Under the UB scenario, that overestimates exposure, a chronic risk could
      not be excluded for nine other pesticides (dithiocarbamates, ethoprophos,
      carbofuran, diazinon, methamidophos, disulfoton, dieldrin, endrin and
      heptachlor). For these pesticides, more sensitive analyses of the main food
      contributors are needed in order to refine exposure assessment.

PMID- 22595192
TI  - MF59 formulated with CpG ODN as a potent adjuvant of recombinant HSP65-MUC1 for
      inducing anti-MUC1+ tumor immunity in mice.
AB  - MF59 is an oil-in-water emulsion adjuvant approved for influenza vaccines for
      human use in Europe. Due to its Th2 inducing properties, MF59 is seldom tested
      for cancer vaccines. In this study, MF59 formulated with a C-type CpG
      oligodeoxynucleotide (YW002) was tested for its Th1 adjuvant activity to induce
      immune responses to HSP65-MUC1, a recombinant fusion protein incorporating a
      mycobacterial heat shock protein (HSP65) and mucin 1, cell surface associated
      (MUC1) derived peptide. Combination of YW002 with MF59 (MF59-YW002) could confer
      a potent Th1 biasing property to the adjuvant, which enhanced the immunogenicity
      of HSP65-MUC1 to induce significantly higher levels of specific IgG2c, increased
      IFN-gamma mRNA expression in splenocytes and the generation of antigen-specific
      cytotoxic T lymphocytes in mice. When prophylactically applied, MF59-YW002
      adjuvant containing HSP65-MUC1 inhibited the growth of MUC1+ B16 melanoma and
      prolonged the survival of tumor-bearing mice. In contrast, adjuvant containing
      MF59 with HSP65-MUC1 in the absence of YW002, promoted the growth of MUC1+ B16
      melanoma in mice. These results suggest that MF59 plus CpG oligodeoxynucleotide
      might be developed as an efficient adjuvant for tumor vaccines against melanoma,
      and possibly other tumors.

PMID- 22595194
TI  - Modulatory effect of mycophenolate mofetil on carrageenan-induced inflammation in
      the mouse air pouch model.
AB  - The treatment of some inflammatory diseases, such as rheumatoid arthritis,
      remains an important target for studies because some patients are refractory to
      conventional treatment. Mycophenolate mofetil (MMF), an immunosuppressive drug,
      has been shown to have a beneficial effect on the therapy of inflammatory and
      autoimmune diseases. In the present study, we aimed to analyse the anti
      inflammatory effect of MMF administered by oral route in the mouse carrageenan
      induced air pouch model. RESULTS: MMF significantly inhibited the influx of
      leukocytes, exudate concentrations (P<0.01), activities of myeloperoxidase (MPO)
      and adenosine deaminase (ADA), levels of nitrite/nitrate (NO(x)) and inducible
      nitric oxide synthase (iNOS) mRNA expression, as well as the levels of mRNA
      expression and proteins of tumor necrosis factor-alpha (TNF-alpha), Interleukin
      beta (IL-1beta) and vascular endothelial growth factor-alpha (VEGF-alpha)
      (P<0.05). These results provide evidence that MMF has an important anti
      inflammatory effect in reducing the influx of leukocytes and exudate
      concentrations. These inhibitory effects are correlated with the inhibition of
      specific pro-inflammatory enzymes (MPO, ADA and iNOS), and the levels of mRNA
      expression and proteins of TNF-alpha, IL-1beta and VEGF-alpha.

PMID- 22595193
TI  - Immunomodulatory properties of beta-sitosterol in pig immune responses.
AB  - The ability to control an immune response for the benefit and production
      efficiency of animals is the objective of immunomodulation in food-producing
      animals; substances that exert this control are called immunomodulators. A
      Spanish product (Inmunicin MAYMO(r)), based on food plant phytosterols, is being
      commercialized as complementary feed. The main component of this product is Beta
      sitosterol (BSS). BSS and its glycoside (BSSG) have been shown to exhibit anti
      inflammatory, anti-neoplasic, anti-pyretic and immune-modulating activity
      demonstrated by in vitro and in vivo experiments. The objective of the present
      study was to characterize the effect of BSS on the pig immune system using in
      vitro cell cultures first and to elucidate whether BSS possesses any in vivo
      activity in fattener pigs after vaccination with porcine reproductive and
      respiratory syndrome virus (PRRSV) modified life vaccine (MLV). Firstly, our in
      vitro results showed that BSS increased viable peripheral blood mononuclear cell
      (PBMC) numbers and it activated swine dendritic cells (DCs) in culture. Secondly,
      pigs treated with phytosterols prior to vaccination with PRRSV-MLV vaccine
      exhibited some changes in immunological parameters at different times post
      vaccination, such as the proliferation ability of PBMC after phytohemaglutinin
      stimulation and increased apolipoprotein A1 plasma concentration which may
      contribute to enhance PRRSV vaccine response. In conclusion, the data in this
      report show that BSS can be considered an immunomodulator in pigs.

PMID- 22595195
TI  - Inhibitory effects of a spinasterol glycoside on lipopolysaccharide-induced
      production of nitric oxide and proinflammatory cytokines via down-regulating MAP
      kinase pathways and NF-kappaB activation in RAW264.7 macrophage cells.
AB  - Extracts from the leaves of Stewartia koreana are known to exhibit strong anti
      inflammatory activity. Investigation of bioactive compounds from S. koreana has
      led to the isolation of 3-O-beta-d-glucopyanosylspinasterol (spinasterol-Glc), a
      spinasterol glycoside. In the present study, we examined the effects of
      spinasterol-Glc on production of nitric oxide (NO) and proinflammatory cytokines
      in LPS-treated RAW264.7 macrophage cells and in mouse models. Our results showed
      that spinasterol-Glc inhibited the production of NO and proinflammatory cytokines
      such as TNF-alpha, IL-6 and IL-1beta in dose-dependent manners in LPS-treated
      RAW264.7 cells. Spinasterol-Glc inhibited the expression of iNOS and the
      proinflammatory cytokine genes. Spinasterol-Glc also inhibited phosphorylation of
      IkappaB-alpha and IKKalpha/beta as well as translocation of NF-kappaB to the
      nucleus. We demonstrated that spinasterol-Glc reduced transcription of the NF
      kappaB minimal promoter and NF-kappaB DNA binding activity. Administration of the
      spinasterol-Glc significantly decreased the plasma levels of these inflammatory
      mediators including TNF-alpha, IL-6 and IL-1beta in LPS-injected mice and
      improved survival of septic mice with lethal endotoxemia. These results suggest
      that spinasterol-Glc has effective inhibitory effects on production of
      inflammatory mediators via inhibition of MAP kinases/NF-kappaB activities, and
      can be used as a potential anti-inflammatory agent for the prevention and
      treatment of inflammatory diseases.

PMID- 22595196
TI  - EPAS1 and EGLN1 associations with high altitude sickness in Han and Tibetan
      Chinese at the Qinghai-Tibetan Plateau.
AB  - High altitude sickness (HAS) occurs among humans visiting or inhabiting high
      altitude environments. Genetic differences in the EPAS1 and EGLN1 genes have been
      found between lowland (Han) and highland (Tibetan) Chinese. Three SNPs within
      EPAS1 and EGLN1 were evaluated in Han and Tibetan patients with acute mountain
      sickness (AMS) and chronic mountain sickness (CMS). We compared 85 patients with
      AMS to 79 Han unaffected with mountain sickness (MS) as well as 45 CMS patients
      to 34 unaffected Tibetan subjects. The three SNPs studied were EPAS1 [ch2:
      46441523 (hg18], EGLN1 (rs480902) and (rs516651). Direct sequencing was used to
      identify individual genotypes for the three SNPs. Age was found to be
      significantly associated with the EPAS1 SNP in the CMS patients while heart rate
      (HR) and oxygen saturation level of hemoglobin (SaO(2)) were found to be
      significantly associated with the EGLN1 (rs480902) SNP in the Han patients with
      AMS. The individuals with CMS were found to diverge significantly for the EPAS1
      SNP compared to their Tibetan control group as measured by genetic distance
      (0.123) indicating positive selection of the EPAS-G allele with age and illness.
      The EGLN1 (rs480902) SNP had a significant correlation with hematocrit (HCT), HR
      and SaO(2) in AMS patients. AMS and CMS were found to be significantly associated
      with the EPAS1 and EGLN1 SNPs compared to their Han and Tibetan control groups,
      respectively, indicating these nucleotide alterations have a physiological effect
      for the development of high altitude sickness.

PMID- 22595198
TI  - Cardiac autonomic profile during rest and working memory load in essential
      hypotensive women.
AB  - To our knowledge, no previous study has provided reliable data supporting a
      different modulation of the Neurovegetative system in essential hypotension. Our
      purpose was to provide, in essential hypotensive women compared to normotensives,
      evidence of a distinct sympathetic and parasympathetic cardiac control.
      Cardiovascular and autonomic indexes derived by impedance cardiography (heart
      rate, HR; pre-ejection period, PEP), photoplethysmographic technique (blood
      pressure, BP) and heart rate variability analysis (high and low frequencies
      power, HF and LF) were continuously collected during rest and mental stress
      condition. Hypotensives, compared to normotensives, exhibited prolonged PEP (low
      sympathetic tone) and elevated HF (high vagal involvement) during rest. In
      addition, they showed cardiovascular (reduced increases in BP and HR) and
      sympathetic (lower reductions of PEP) hypo-reactivity to the task. Furthermore, a
      lower sympathetic reactivity in hypotensives was associated to a poorer task
      performance. Essential hypotension was characterized by a low sympathetic and
      high parasympathetic tone. In addition, a reduced sympathetic nervous system
      reactivity suggests the main role of the Neurovegetative system in mediating the
      relationship between blood pressure and cognitive performance in hypotensives.

PMID- 22595199
TI  - An 81-year-old patient with distant metastasis of invasive lobular carcinoma
      occurring 41 years after mastectomy.

PMID- 22595200
TI  - Myalgic phenotype and preserved muscle strength in adult-onset acid maltase
      deficiency.
AB  - Adult-onset acid maltase deficiency is a rare disorder characterized by
      progressive proximal muscle weakness and early respiratory insufficiency. We
      present a case of a 53-year-old woman who presented with several years of severe,
      diffuse myalgia and no evidence of weakness on examination. Further testing
      revealed a mildly elevated serum creatine kinase, a subtle vacuolar myopathy,
      decreased skeletal muscle alpha-glucosidase activity, and causative mutations in
      the responsible GAA gene. While likely very uncommon, adult-onset acid maltase
      deficiency may present with diffuse strength-sparing myalgia.

PMID- 22595201
TI  - CAV3 T78M mutation as polymorphic variant in South Italy.

PMID- 22595202
TI  - Mutant HSPB8 causes protein aggregates and a reduced mitochondrial membrane
      potential in dermal fibroblasts from distal hereditary motor neuropathy patients.
AB  - Missense mutations in the small heat shock protein HSPB8 cause distal hereditary
      motor neuropathy (dHMN) and axonal Charcot-Marie-Tooth disease (CMT2L). We
      previously demonstrated that, despite the ubiquitous expression of HSPB8, motor
      neurons appear to be predominantly affected by HSPB8 mutations. Here, we studied
      the effect of mutant HSPB8 in primary fibroblast cultures derived from dHMN
      patients' skin biopsy. In early passage cultures, we observed in all patients'
      fibroblasts HSPB8 protein aggregates that were not detected in control cells.
      After applying heat shock stress on the patients' early passage cultured cells,
      the protein aggregates coalesced into larger formations, while in control cells a
      homogenous upregulation of HSPB8 protein expression was seen. We also found a
      reduction in the mitochondrial membrane potential in the early passage cultures.
      After three months in culture, the number of cells with aggregates had become
      indistinguishable from that in controls and the mitochondrial membrane potential
      had returned to normal. These results emphasize the possible drawbacks of using
      patients' non-neuronal cells to study neuropathological disease mechanisms.

PMID- 22595203
TI  - Healthy ageing in women: is moderate drinking the secret ingredient?

PMID- 22595205
TI  - Computer simulation of electric field variations due to movements of electric
      charges.
AB  - Simulations were carried out for the orbit of electron-induced secondary
      electrons around a charged microfibril of a sciatic nerve tissue. In order to set
      the parameters for the simulation, the shape of the microfibril was determined
      from a transmission electron microscopy image, while the electric potential on
      the surface of the charged microfibril was evaluated from a reconstructed phase
      image obtained with electron holography. On the other hand, the passing point and
      the angle of secondary electrons at the microfibril surface were determined from
      a reconstructed amplitude image. Eventually, simulation of orbits of secondary
      electrons was carried out by changing the kinetic energy of the secondary
      electrons. Under the given conditions, the orbit of secondary electrons with a
      kinetic energy of 29.6 eV fits the observations. If there are thin layers of
      electrons, the secondary electrons do not reach the surface but they go over it
      due to the repulsive Coulomb force resulting in successive revolving motion
      around the charged microfibril. Furthermore, the electric field variation due to
      the movement of the electric charges resulting from the specimen drift is also
      discussed briefly comparing it with electron holography data.

PMID- 22595204
TI  - A systematic review of body fat distribution and mortality in older people.
AB  - We conducted a systematic review investigating body fat distribution in older
      adults and its association with morbidity and mortality. Our search yielded 2702
      citations. Following three levels of screening, 25 studies were selected to
      evaluate the association between body fat distribution and comorbidity, and 17
      studies were used in the mortality analysis. Most of the selected studies in our
      analyses used anthropometric measures, e.g., body mass index (BMI), waist
      circumference, and waist-hip ratio; relatively few studies used direct measures,
      such as body fat/lean mass, and percentage body fat. Studies reported
      inconsistent findings regarding the strongest predictor(s) of morbidity and
      mortality. However, the majority of studies suggested that BMI per se was not the
      most appropriate predictor of morbidity and mortality in the elderly because of
      its inability to discern or detect age-related body fat redistribution. In
      addition, studies using BMI found that the optimal BMI range for the lowest
      mortality in the elderly was overweight (25 kg/m(2)<=BMI<30 kg/m(2)) or mildly
      obese (30 kg/m(2)<=BMI<35 kg/m(2)). Our findings suggest that the current
      clinical guidelines, recommending that overweight and obesity are major risk
      factors for increased morbidity and mortality are not applicable to this
      population. Therefore, the central message of this review is to advise the
      government to establish new guidelines specifically for this population, using a
      combination of body fat distribution measurements, and to certify that these
      guidelines will not be applied to inappropriate populations.

PMID- 22595206
TI  - Chronic heart failure modifies the response to positive end-expiratory pressure
      in patients with chronic obstructive pulmonary disease.
AB  - INTRODUCTION: Potentially beneficial effects of positive end-expiratory pressure
      (PEEP) in patients with chronic obstructive pulmonary disease (COPD) must be
      balanced against further overinflation and increased alveolar dead space.
      Concurrent chronic heart failure (CHF) is common and can lead to changes in lung
      that can reduce the detrimental effects of PEEP. OBJECTIVE: The aim of this study
      was to compare the effect of PEEP on volumetric capnography, blood gases,
      pulmonary mechanics, and vital signs in subjects with either COPD (n = 13) or
      COPD + CHF (n = 7) during pressure support ventilation. METHODS: Positive end
      expiratory pressure was administered at 0, 5, 10, 15, and 0 cm H(2)O for 15
      minutes with pressure support maintained at 10 cm H(2)O. Data are expressed as
      mean +/- SD, and the effect of PEEP and differences between COPD alone and COPD +
      CHF were tested with repeated-measures analysis of variance. RESULTS: Subjects
      were elderly (72.5 +/- 13.3 years) with severe COPD (force expired volume in 1
      second, 1.3 +/- 0.6L; force expired volume in 1 second/force vital capacity, 40%
      +/- 15%). With increasing PEEP in COPD subjects, dead space ratio increased (P <
      .001), minute alveolar ventilation decreased (P = .001), and Paco(2) increased (P
      = .013), with no change in COPD + CHF subjects. Subjects with COPD + CHF had
      improvement in Pao(2) and lower mean arterial pressure, whereas both were
      unchanged in subjects with COPD alone. CONCLUSION: In subjects with severe COPD
      alone, caution must be used when administering PEEP 10 cm H(2)O or greater.
      Subjects with COPD + CHF may benefit from higher levels of PEEP.

PMID- 22595207
TI  - R/EBcoexpress: an empirical Bayesian framework for discovering differential co
      expression.
AB  - R/EBcoexpress implements the approach of Dawson and Kendziorski using R, a freely
      available, open source statistical programming language. The approach identifies
      differential co-expression (DC) by examining the correlations among gene pairs
      using an empirical Bayesian approach, producing a false discovery rate controlled
      list of DC pairs. This interrogation of DC gene pairs complements but is distinct
      from differential expression analyses, under the general goal of understanding
      differential regulation across biological conditions. AVAILABILITY AND
      IMPLEMENTATION: R/EBcoexpress is freely available and hosted on Bioconductor; a
      source file and vignette may be found at
      http://www.bioconductor.org/packages/release/bioc/html/EBcoexpress.html

PMID- 22595208
TI  - Robust identification of transcriptional regulatory networks using a Gibbs
      sampler on outlier sum statistic.
AB  - MOTIVATION: Identification of transcriptional regulatory networks (TRNs) is of
      significant importance in computational biology for cancer research, providing a
      critical building block to unravel disease pathways. However, existing methods
      for TRN identification suffer from the inclusion of excessive 'noise' in
      microarray data and false-positives in binding data, especially when applied to
      human tumor-derived cell line studies. More robust methods that can counteract
      the imperfection of data sources are therefore needed for reliable identification
      of TRNs in this context. RESULTS: In this article, we propose to establish a link
      between the quality of one target gene to represent its regulator and the
      uncertainty of its expression to represent other target genes. Specifically, an
      outlier sum statistic was used to measure the aggregated evidence for regulation
      events between target genes and their corresponding transcription factors. A
      Gibbs sampling method was then developed to estimate the marginal distribution of
      the outlier sum statistic, hence, to uncover underlying regulatory relationships.
      To evaluate the effectiveness of our proposed method, we compared its performance
      with that of an existing sampling-based method using both simulation data and
      yeast cell cycle data. The experimental results show that our method consistently
      outperforms the competing method in different settings of signal-to-noise ratio
      and network topology, indicating its robustness for biological applications.
      Finally, we applied our method to breast cancer cell line data and demonstrated
      its ability to extract biologically meaningful regulatory modules related to
      estrogen signaling and action in breast cancer. AVAILABILITY AND IMPLEMENTATION:
      The Gibbs sampler MATLAB package is freely available at
      http://www.cbil.ece.vt.edu/software.htm. CONTACT: xuan@vt.edu SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 22595209
TI  - flowPeaks: a fast unsupervised clustering for flow cytometry data via K-means and
      density peak finding.
AB  - MOTIVATION: For flow cytometry data, there are two common approaches to the
      unsupervised clustering problem: one is based on the finite mixture model and the
      other on spatial exploration of the histograms. The former is computationally
      slow and has difficulty to identify clusters of irregular shapes. The latter
      approach cannot be applied directly to high-dimensional data as the computational
      time and memory become unmanageable and the estimated histogram is unreliable. An
      algorithm without these two problems would be very useful. RESULTS: In this
      article, we combine ideas from the finite mixture model and histogram spatial
      exploration. This new algorithm, which we call flowPeaks, can be applied directly
      to high-dimensional data and identify irregular shape clusters. The algorithm
      first uses K-means algorithm with a large K to partition the cell population into
      many small clusters. These partitioned data allow the generation of a smoothed
      density function using the finite mixture model. All local peaks are exhaustively
      searched by exploring the density function and the cells are clustered by the
      associated local peak. The algorithm flowPeaks is automatic, fast and reliable
      and robust to cluster shape and outliers. This algorithm has been applied to flow
      cytometry data and it has been compared with state of the art algorithms,
      including Misty Mountain, FLOCK, flowMeans, flowMerge and FLAME. AVAILABILITY:
      The R package flowPeaks is available at https://github.com/yongchao/flowPeaks.
      CONTACT: yongchao.ge@mssm.edu SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 22595211
TI  - Recent trends in the epidemiology of endomyocardial fibrosis in Africa.

PMID- 22595210
TI  - CodonLogo: a sequence logo-based viewer for codon patterns.
AB  - MOTIVATION: Conserved patterns across a multiple sequence alignment can be
      visualized by generating sequence logos. Sequence logos show each column in the
      alignment as stacks of symbol(s) where the height of a stack is proportional to
      its informational content, whereas the height of each symbol within the stack is
      proportional to its frequency in the column. Sequence logos use symbols of either
      nucleotide or amino acid alphabets. However, certain regulatory signals in
      messenger RNA (mRNA) act as combinations of codons. Yet no tool is available for
      visualization of conserved codon patterns. RESULTS: We present the first
      application which allows visualization of conserved regions in a multiple
      sequence alignment in the context of codons. CodonLogo is based on WebLogo3 and
      uses the same heuristics but treats codons as inseparable units of a 64-letter
      alphabet. CodonLogo can discriminate patterns of codon conservation from patterns
      of nucleotide conservation that appear indistinguishable in standard sequence
      logos. AVAILABILITY: The CodonLogo source code and its implementation (in a local
      version of the Galaxy Browser) are available at http://recode.ucc.ie/CodonLogo
      and through the Galaxy Tool Shed at http://toolshed.g2.bx.psu.edu/.

PMID- 22595212
TI  - Economic burden of acute lower respiratory tract infection in South African
      children.
AB  - BACKGROUND: Acute lower respiratory tract infections (ALRTI) are a leading cause
      of childhood mortality, but there are few data on disease costs in developing
      countries. OBJECTIVES: This study's purpose was to analyse ALRTI's costs-of
      illness and economic burden in urban South African children. METHODS: ALRTI costs
      of-illness (expressed in US$ 2010) at a tertiary hospital were measured using a
      micro-costing approach nested within a clinical trial. Demographic,
      epidemiological and data on use of health resources were integrated with costs-of
      illness to estimate the economic burden of ALRTI in urban South African children
      aged <5 years. RESULTS: 745 children experiencing 858 ALRTI episodes were
      studied. 338 (39.4%), 513 (59.8%) and 7 (0.8%) episodes were managed in short
      stay, paediatric ward and intensive care settings, respectively. Mean lengths of
      stay in short-stay, paediatric ward and intensive care (ICU) were 1.4, 8.1 and
      14.4 days, respectively. The societal costs-of-illness per ALRTI episode managed
      in short-stay and paediatric ward settings, respectively, were US$266 (95% CI 245
      286) and 1287 (95% CI 1174-1401) in HIV-infected patients, and US$257 (95% CI 247
      267) and 1032 (95% CI 931-1133) in HIV-uninfected patients. Family costs were not
      collected in ICUs. ICU direct medical costs were US$5968 (95% CI 4025-8056) in
      HIV-uninfected patients and US$7849 in one HIV-infected patient. Under-5 children
      experienced an estimated 424,220 episodes annually of ALRTI. ALRTI treatment cost
      the public health system an estimated US$28,975,000 while an additional
      US$539,000 of costs were borne by families. CONCLUSION: ALRTIs in children <5
      years impose a heavy economic burden on families and the South African public
      health-care system.

PMID- 22595213
TI  - Nutritional status and its response to treatment of children, with and without
      HIV infection, hospitalized for the management of tuberculosis.
AB  - BACKGROUND: The association of childhood tuberculosis (TB) and malnutrition is
      known, but treatment response, the influence of the acute-phase response (APR)
      and concomitant HIV infection are not well documented. AIM: To evaluate the
      nutritional response and APR in HIV-infected and uninfected children hospitalised
      for the treatment of TB and receiving standard anti-tuberculosis chemotherapy.
      METHODS: During a study of the pharmacokinetics of standard anti-tuberculosis
      agents, anthropometric parameters were measured and blood concentrations of
      nutrients and C-reactive protein (CRP) determined at 1 and 4 months after
      initiation of chemotherapy. RESULTS: 24 HIV-infected and 34 HIV-uninfected
      children were studied. On enrollment, 31.6% of HIV-infected and 2.9% of HIV
      uninfected children were underweight, and 31.6% and 14.7%, respectively, were
      stunted. Mean values of weight, height/length, head circumference and mid-upper
      arm circumference on enrollment and at 4-month assessment in HIV-infected and
      uninfected children did not differ. Mean triceps skinfold (TSF) (8.17 and 9.73
      cm) and subscapular skinfold (SSF) thicknesses (5.75 and 7.5 cm) on enrollment
      differed significantly (P = 0.03 and P = 0.003); by 4 months, TSF had declined to
      5.97 cm (P<0.001) and 8.87 cm (P = 0.05), respectively, and SSF to 5.57 cm (P =
      0.79) and 6.73 cm (P = 0.04); the arm muscle area (AMA) was low in a majority of
      children on enrollment and remained so at the second assessment. CRP was raised
      in 66.6% and 53.3% of HIV-infected and -uninfected children on enrollment, but at
      4-month assessment was raised in 63.2% and 15.2%, respectively. Other
      micronutrient and haematological findings probably reflect an APR, but no
      children had sub-normal zinc or magnesium values; most selenium and vitamin C and
      E values were normal. An elevated platelet count (> 420 * 10(9)/L) was
      significantly more common in HIV-uninfected children, and was still raised in 39%
      at 4 months. CONCLUSION: A majority of HIV-infected and uninfected children had
      an APR but it had resolved by 4 months in most HIV-uninfected children. In both
      groups, low and declining skinfolds and a persistently low AMA indicate a
      persistent disturbance of fat and protein metabolism, despite successful
      chemotherapy.

PMID- 22595214
TI  - Epidemiology of Burkitt's lymphoma in Northwest Province, Cameroon, 2003-2010.
AB  - BACKGROUND: Burkitt's lymphoma (BL) is an aggressive non-Hodgkin's lymphoma
      endemic to regions of Africa. Cases are thought to be typically found in low
      lying, humid regions where malaria is rife. AIMS AND OBJECTIVES: To investigate
      the clinical characteristics of BL, its incidence and relationship with malarial
      incidence in Northwest (NW) Province, Cameroon. METHODS: Data on BL were
      collected from the three tertiary referral centres for BL treatment in NW
      Province, Cameroon. Data on malaria were collected from the Delegation of Public
      Health in Bamenda, NW Province. Data were collected between March and May 2010.
      RESULTS: 471 cases of BL were identified. The St Jude's stage of patients at
      presentation was as follows: stage I, 14.4% (43/299); stage II, 8.4% (25/299);
      stage III, 69.9% (209/299); stage IV, 7.4% (22/299). The incidences of BL per
      100,000 children <15 years of age from 2005 to 2009 were as follows: 2005, 3.01
      (29); 2006, 2.02 (20); 2007, 2.45 (25); 2008, 2.38 (25); 2009, 3.06 (33). The
      average incidence in NW Province was 2.58. In the Ndop plain, Ngo-Ketunjia, the
      incidences of BL were as follows: 2005, 10.3 (10); 2006, 3.00 (3); 2007, 1.95
      (2); 2008, 2.84 (3); 2009, 4.60 (5). The average incidence was 4.54/100,000
      children <15 years of age. Statistical analysis demonstrated a sinusoidal
      distribution of malaria cases throughout the year (P<0.00), with a peak incidence
      on 10 April. Conversely, no sinusoidal distribution of BL cases was demonstrated
      throughout the year (P = 0.09). CONCLUSION: No relationship was demonstrated
      between an acute malarial infection and BL. Significant clustering was found,
      with the low-lying Ndop plain of Ngo-Ketunjia having an incidence of BL nearly
      twice that elsewhere in the region. The study demonstrates that the incidence of
      BL in NW Province, Cameroon remains one of the highest documented in the world.

PMID- 22595215
TI  - Endomyocardial fibrosis: the first report from Malawi.
AB  - Endomyocardial fibrosis (EMF) is a restrictive cardiomyopathy of unknown
      aetiology previously unreported in Malawi. Six Malawian children (three males)
      aged between 12 and 16 years who presented with EMF in 2009/10 are described.
      Five were from the Southern Highlands.

PMID- 22595216
TI  - Budd-Chiari disease in infancy: three cases.
AB  - Budd-Chiari syndrome (BCS) is rare in infancy. Three cases are presented. Case 1,
      an 8-month-old boy, presented with abdominal distension and oliguria. Doppler
      study of the abdomen showed ascites, hepatomegaly and normal hepatic veins.
      However, a CT scan demonstrated hepatic vein thrombosis.  Case 2, a 5-month-old
      boy, presented with abdominal distension and diarrhoea. Ultrasound of the abdomen
      showed hepatic vein thrombosis and hepatomegaly. Case 3, a 7-month-old girl,
      presented with abdominal distension, diarrhoea and oliguria. Ultrasound of the
      abdomen showed hepatomegaly and  obstructed hepatic veins. None of the cases had
      fever or jaundice before presentation. Case 1 developed fungal septicaemia and
      was lost to follow-up. Cases 2 and 3 succumbed to the disease before further
      intervention.

PMID- 22595217
TI  - Morbidity of ABO haemolytic disease in the newborn.
AB  - BACKGROUND: Better understanding of the clinical characteristics of ABO
      haemolytic disease in neonates helps optimise care. OBJECTIVE: To assess the
      morbidity associated with maternal-neonatal ABO incompatibility. METHODS:
      Neonates with blood groups A or B born to mothers with blood group O with
      simultaneous rhesus blood factor compatibility were studied prospectively.
      Maternal and neonatal details, direct Coomb's test (DCT) on the cord blood, onset
      and progression of jaundice, and requirement and duration of phototherapy were
      studied. Neonates requiring phototherapy were considered to have significant
      hyperbilirubinaemia, and peripheral smear, reticulocyte count and haematocrit
      values were obtained. ABO haemolytic disease of the newborn (ABO HDN) is defined
      as a newborn with a positive DCT and/or laboratory evidence of haemolysis such as
      reticulocytosis and spherocytes on blood smear. RESULTS: Of 878 deliveries, 151
      (17.3%) neonates were ABO incompatible with their mothers. The proportions who
      were O-A and O-B incompatible were 50.4% and 49.6%, respectively. Forty-six
      (30.4%) had significant hyperbilirubinaemia (119.7-256.5 mmol/L) and required
      phototherapy, 26 (34.2%) of them in the O-A group and 20 (26.6%) in the O-B
      group. None required exchange transfusion. Jaundice was detected within the first
      24 hours in 47.8%. Of 46 newborns who required phototherapy, 25 (54.3%) had
      laboratory evidence of haemolysis. DCT was positive in 1.9% of ABO-incompatible
      newborns. There was no significant difference in the incidence and severity of
      haemolysis between the O-A and O-B-incompatible neonates. Neonates with
      haemolysis required phototherapy significantly earlier and for longer than
      neonates without haemolysis (P<0.001). CONCLUSIONS: ABO incompatibility was
      observed in 17.3% of pregnancies with almost equal O-A and O-B frequency. About a
      third of infants had significant hyperbilirubinaemia. There was no difference in
      severity between those with O-A and O-B HDN.

PMID- 22595218
TI  - Factors associated with extreme hyperbilirubinaemia in neonates at the University
      Hospital of the West Indies.
AB  - AIM: To determine factors associated with extreme hyperbilirubinaemia in neonates
      at the University Hospital of the West Indies. METHODS: A retrospective review of
      all neonates with hyperbilirubinaemia requiring medical intervention at the
      University Hospital of the West Indies between 1 January 2006 and 30 June 2007
      was performed. Factors associated with extreme hyperbilirubinaemia were
      determined using multiple logistic regression models. RESULTS: A total of 170
      neonates fulfilled the inclusion criteria for the study and 15 (9%) of them had
      extreme hyperbilirubinaemia. The majority (97, 57%) were term infants and 103
      (61%) were male. Exclusively breastfed neonates were more likely to have extreme
      hyperbilirubinaemia (OR 2.6, 95% CI 0.01-0.6). Neonates whose mothers received
      oxytocin during labour (OR 2.7, 95% CI 0.02-0.3) and those who were G6PD
      deficient (OR 2.6, 95% CI 0.01-0.5) were more likely to have extreme
      hyperbilurubinaemia. CONCLUSION: Exclusive breastfeeding, oxytocin use in the
      mother during labour and G6PD deficiency in the infant were found to be factors
      associated with extreme hyperbilirubinaemia.

PMID- 22595219
TI  - Elective high-frequency oscillatory ventilation in preterm neonates: a
      preliminary investigation in a developing country.
AB  - BACKGROUND: Elective high-frequency oscillatory ventilation (HFOV) in preterm
      infants is known to be as effective as conventional ventilation in the prevention
      of bronchopulmonary dysplasia without the risk of increased mortality or brain
      damage. OBJECTIVE: To document  the feasibility and safety of early use of HFOV
      in preterm neonates with respiratory distress syndrome (RDS) in a resource
      limited setting. The primary outcome was survival or death, and the secondary
      outcome included complication rates observed among the two groups, HFOV and
      synchronised  intermittent mandatory ventilation (SIMV). METHOD: Prospective,
      single-centre, non-crossover, and case-control design comparing outcome of HFOV
      with synchronised intermittent mandatory ventilation (SIMV) in preterm neonates
      with RDS. RESULTS: Preterm infants with RDS and  a gestational age of 26-36 weeks
      were ventilated using either SIMV or HFOV soon after intubation. Twenty-two
      neonates in the HFOV group and 27 in the SIMV group were considered in the final
      analysis. Mortality was similar in both the groups for each gestational-age
      subgroup. There were  no statistically significant differences in complication
      rates between the groups. CONCLUSION: Elective ventilation with HFOV to provide
      pulmonary support for preterm neonates is feasible in a resource-limited country
      such as India.

PMID- 22595220
TI  - Normal oscillometric heart rate of term African infants in the early days of
      life.
AB  - BACKGROUND: Heart rate (HR) measurement is an important means of evaluating
      clinical status of newborns. Differences in HR between caucasian and negroid
      infants have been reported. Clinical estimation of HR is less accurate than
      estimates using devices. AIM: To establish the normal HR of term negroid newborns
      in the early days of life using an oscillometric device. METHODS: The mean of
      three HR readings of consecutively recruited term newborns was obtained with
      Dinamp 8100 monitor (Critikon, Tampa, FL). On recruitment, the infants were aged
      between 1 and 4 days. Gestational age was determined by menstrual dates and the
      Dubowitz method. RESULTS: A total of 473 term newborns were recruited, 229
      (48.4%) of whom were males. Median HR was 132 (range 90-189) beats per minute
      (bpm). The lowest median HR (130 bpm) was obtained on the 3rd day of life and
      this was significantly different from the highest value of 138 bpm recorded on
      the 4th day of life (P = 0.025). The 5th and 95th percentiles were 111 and 158
      bpm, respectively. CONCLUSION: The lower limit of the range of oscillometrically
      generated normal HR in term African newborns in the early days of life is lower
      than that which is commonly used in clinical practice.

PMID- 22595221
TI  - Congenital syphilis mimicking haematological or oncological disorders.
AB  - Congenital syphilis (CS) presents with a variety of clinical manifestations,
      including haematological abnormalities. The haematological abnormalities of early
      CS are variable and non-specific, and can mimic several haematological diseases
      of infancy. Two infants aged 3 and 7 months  who presented with CS and
      haematological abnormalities are reported. With the worldwide increase of this
      disease, it is important that paediatricians consider congenital syphilis early
      in the differential diagnosis of infants presenting with unexplained
      haematological abnormalities or suspected  malignancy.

PMID- 22595222
TI  - Kartagener syndrome associated with mesangioproliferative glomerulonephritis.
AB  - An 11-year-old girl with clinical features of Kartagener syndrome presented with
      signs of acute glomerulonephritis. Blood urea and creatinine were mildly elevated
      and anti-streptolysin O and C3 levels were normal. Renal biopsy demonstrated
      mesangial proliferation and direct immunofluorescence  showed IgM and C3
      deposits. This appears to be the first report of Kartagener syndrome in
      association with mesangioproliferative glomerulonephritis. The literature is
      reviewed and the possible mechanisms for this association are discussed.

PMID- 22595223
TI  - Rickets associated with ichthyosis.
AB  - Nutritional rickets in disorders of keratinisation is very rare. A 12-year-old
      girl with autosomal dominant ichthyosis vulgaris is reported who presented with
      tetany and a waddling gait. She had the classic clinical, biochemical and
      radiological features of rickets. She was treated  with vitamin D and calcium
      supplements together with keratolytic and emollient agents, which was followed by
      biochemical and clinical remission. This appears to be the first report of
      rickets associated with autosomal dominant ichthyosis vulgaris.

PMID- 22595224
TI  - HSV-2 meningitis disseminated from a herpetic whitlow.
AB  - HSV-2 meningitis is uncommon in childhood and is mainly associated with genital
      lesions or a history of sexual abuse. A 7-year-old boy with recurrent herpetic
      whitlow developed HSV-2 meningitis. HSV-2 was identified in the CSF by PCR. In
      children with herpetic whitlow, the risk of HSV-2,  although rare, should be
      considered.

PMID- 22595225
TI  - Jejunal tuberculosis in a 10-year-old girl.
AB  - Abdominal tuberculosis in children usually presents with involvement of the
      peritoneum, lymph nodes or gastro-intestinal tract. Disease of the gastro
      intestinal tract is commonest in the ileocaecal region. A 10-year-old girl
      presented with abdominal pain and fever of 15 days duration.  Abdominal CT
      detected dilated small bowel loops with enlarged mesenteric nodes and barium meal
      follow-through demonstrated a small annular stricture in the jejunum, suggestive
      of jejunal tuberculosis. She was treated with anti-tuberculous chemotherapy and
      corticosteroids, to which she made  a good response. Tuberculosis of the jejunum
      is rare in children.

PMID- 22595226
TI  - Histopathology of naturally occurring and surgically induced osteoarthritis in
      mice.
AB  - OBJECTIVE: The morphology of lesions in mouse models of osteoarthritis (OA) has
      not been comprehensively characterized, in part because current histological
      assessments of OA focus primarily on articular cartilage (AC). In the present
      study, sections of murine stifle joints with naturally occurring (aged animals)
      and surgically induced (destabilized medial meniscus, DMM) OA were examined using
      a newly developed histological grading scheme that includes quantitative
      measurements and semiquantitative grades to evaluate multiple joint tissues.
      DESIGN: The data collected was analyzed using Principal Components Analysis
      (PCA); factor scores for each joint were generated. Individual parameters and
      factor scores were compared between surgical groups and among age groups. For
      comparison, the original Mankin Histological-Histochemical Grading System (HHGS)
      also was applied. RESULTS: Overall, lesions were most severe in the medial tibial
      plateaus. Significant changes in AC and neighboring bone were identified in
      surgically induced models and in naturally occurring disease. Mean factor scores
      provided a comprehensive evaluation of joint changes. An important new finding
      was that chondrocyte cell death within the AC was a commonly identified lesion
      and its extent significantly increased with age. While the Mankin HHGS detected
      significant overall differences in OA severity between surgical groups, it was
      not sensitive in detecting age-related differences, nor did it provide
      information regarding changes in individual tissues. CONCLUSION: These results
      demonstrate the utility of this newly developed murine OA grading scheme in
      identifying lesions in AC and in other joint tissues. Surgically induced changes
      were similar to those occurring naturally with aging.

PMID- 22595228
TI  - Serum adipokines in osteoarthritis; comparison with controls and relationship
      with local parameters of synovial inflammation and cartilage damage.
AB  - OBJECTIVE: Adipose tissue is an endocrine tissue releasing adipokines suggested
      to be involved in the pathogenesis of osteoarthritis (OA). Nevertheless, their
      relative contribution and exact mechanisms are still ambiguous. The aim of this
      study is to compare serum adipokine levels between end-stage knee OA patients and
      controls and to relate these serum levels to local parameters of cartilage damage
      and synovial inflammation. METHODS: Serum was collected from 172 severe knee OA
      patients, shortly before total knee replacement (TKR) surgery and from 132
      controls without radiographic knee OA [Kellgren & Lawrence (K&L) = 0]. Serum
      adiponectin, leptin, and resistin levels were measured by enzyme-linked
      immunosorbent assay (ELISA). Cartilage and synovial tissue were collected at TKR
      surgery and assessed for cartilage degeneration and synovial inflammation by
      histochemistry and biochemical analyses. RESULTS: The adipokine levels were all
      distinctly higher in OA patients as compared to controls. Especially adiponectin
      and leptin were associated with female gender (stand beta = 0.239 and 0.467,
      respectively, P < 0.001) and body mass index (BMI) (stand beta = -0.189 and
      0.396, respectively, P < 0.001). No associations between serum levels of
      adipokines and cartilage damage (histochemistry, proteoglycan content) were found
      whereas weak but positive associations with synovial inflammation were found
      [adiponectin and interleukin-1beta (IL-1beta), stand beta = 0.172, P = 0.02;
      resistin and histology, stand beta = 0.183, P = 0.034, adjusted for
      demographics]. CONCLUSION: This study suggests an important involvement of
      adipokines in OA patients considering their high serum levels compared to
      controls. Associations of systemic adipokines with local synovial tissue
      inflammation were found, although not represented by similar relations with
      cartilage damage, suggesting that adipokines are of relevance in the inflammatory
      component of OA.

PMID- 22595229
TI  - Predicting the place of out-of-hours care--a market simulation based on discrete
      choice analysis.
AB  - BACKGROUND: Increasing cost pressure and changing patients' needs in the
      healthcare sector have led to new delivery models for primary care. Researchers
      and practitioners need to establish innovative methods to obtain insights into
      patients' preferences and effectiveness of healthcare services. AIM: This study
      reveals the crucial decision criteria of patients in choosing out-of-hours
      services and provides a projection of a future market share of the newly
      established central out-of-hours service, called General Practitioner
      Cooperative. DESIGN: A computer-aided discrete choice experiment. METHOD:
      Respondents were 350 patients in a European city who decided for a service when
      confronted with a medical emergency in an out-of-hours case; two scenarios called
      'adult' and 'child', describing the persons requiring medical assistance, were
      used to increase generalizability. RESULTS: The two most important attributes
      were 'explanation by the doctor' and 'waiting time' while the others -
      'availability of technical equipment', 'ease of access', 'type of consultation'
      and 'payment method' - were of less importance. The market share projections
      predict that the new General Practitioner Cooperative will capture about one
      third of the market ('adult': 39.1%, 'child': 31.3%), ahead of the emergency
      department, the second most preferred service ('adult': 32.7%, 'child': 30.7%).
      CONCLUSIONS: This study quantifies the adoption of a new medical service. As a
      result, it extends current research approaches on eliciting and matching
      patient's needs and assists policy makers in establishing adequate service
      capacities.

PMID- 22595230
TI  - Machine learning on-a-chip: a high-performance low-power reusable neuron
      architecture for artificial neural networks in ECG classifications.
AB  - Artificial neural networks (ANNs) are a promising machine learning technique in
      classifying non-linear electrocardiogram (ECG) signals and recognizing abnormal
      patterns suggesting risks of cardiovascular diseases (CVDs). In this paper, we
      propose a new reusable neuron architecture (RNA) enabling a performance-efficient
      and cost-effective silicon implementation for ANN. The RNA architecture consists
      of a single layer of physical RNA neurons, each of which is designed to use
      minimal hardware resource (e.g., a single 2-input multiplier-accumulator is used
      to compute the dot product of two vectors). By carefully applying the principal
      of time sharing, RNA can multiplexs this single layer of physical neurons to
      efficiently execute both feed-forward and back-propagation computations of an ANN
      while conserving the area and reducing the power dissipation of the silicon. A
      three-layer 51-30-12 ANN is implemented in RNA to perform the ECG classification
      for CVD detection. This RNA hardware also allows on-chip automatic training
      update. A quantitative design space exploration in area, power dissipation, and
      execution speed between RNA and three other implementations representative of
      different reusable hardware strategies is presented and discussed. Compared with
      an equivalent software implementation in C executed on an embedded
      microprocessor, the RNA ASIC achieves three orders of magnitude improvements in
      both the execution speed and the energy efficiency.

PMID- 22595227
TI  - Enhanced COMP catabolism detected in serum of patients with arthritis and animal
      disease models through a novel capture ELISA.
AB  - OBJECTIVE: The study aimed determining whether assessment of cartilage oligomeric
      matrix protein (COMP) degradation products could serve as a serological disease
      course and therapeutic response predictor in arthritis. METHODS: We generated a
      panel of monoclonal antibodies against COMP fragments and developed a novel
      capture enzyme-linked immunosorbent assay (ELISA) for detecting COMP fragments in
      patients with osteoarthritis (OA) and rheumatoid arthritis (RA). This test was
      also used to monitor COMP fragments in surgically-induced OA, collagen-induced
      arthritis (CIA), and tumor necrosis factor (TNF) transgenic animal models.
      RESULTS: Compared with a commercial COMP ELISA kit that detected no significant
      difference in COMP levels between OA and control groups, a significant increase
      of the COMP fragments were noted in the serum of OA patients assayed by this
      newly established ELISA. In addition, serum COMP fragment levels were well
      correlated with severity in OA patients and the progression of surgically-induced
      OA in murine models. Furthermore, the serum levels of COMP fragments in RA
      patients, mice with CIA, and TNF transgenic mice were significantly higher when
      compared with their controls. Interestingly, treatment with TNFalpha inhibitors
      and methotrexate led to a significant decrease of serum COMP fragments in RA
      patients. Additionally, administration of Atsttrin [Tang, et al., Science
      2011;332(6028):478] also resulted in a significant reduction in COMP fragments in
      arthritis mice models. CONCLUSION: A novel sandwich ELISA is capable of
      reproducibly measuring serum COMP fragments in both arthritic patients and rodent
      arthritis models. This test also provides a valuable means to utilize serum COMP
      fragments for monitoring the effects of interventions in arthritis.

PMID- 22595232
TI  - Perinatal iodine deficiency and hypothyroidism increase cell apoptosis and alter
      doublecortin and reelin protein expressions in rat cerebellum.
AB  - BACKGROUND AND AIMS: Adequate thyroid hormone is critical for cerebellar
      development. Developmental hypothyroidism induced by iodine deficiency during the
      perinatal period results in permanent impairments of cerebellar development with
      an unclear mechanism. In the present study we investigated effects of perinatal
      iodine deficiency and hypothyroidism on cerebellar cell apoptosis, doublecortin
      (Dcx) and reelin. Apoptosis is an essential part of neural development. Dcx and
      reelin are two important molecules involved in neuronal migration, structure, and
      development in cerebellum. METHODS: Two developmental rat models were created by
      administering dam rats with either iodine-deficient diet or propylthiouracil
      (PTU, 5 ppm or 15 ppm)-added drinking water from gestational day (GD) 6 until
      postnatal day (PND) 28. TUNEL assay and protein levels of Dcx and reelin in
      cerebella were assessed on PND14, 21 and 28. RESULTS: Apoptotic cells were
      increased in the iodine-deficient and PTU-treated rats. Dcx protein levels in the
      cerebella of iodine-deficient and PTU-treated rats were significantly
      downregulated on PND14. Interestingly, iodine deficiency and PTU treatment
      upregulated the levels of Dcx protein on PND21 and 28. Reelin expressions in
      iodine-deficient and PTU-treated rats were significantly decreased on PND14 and
      21. On PND28, reelin expressions of three treated groups were still lower than
      control group, although without significant difference. CONCLUSIONS: These
      findings may implicate alterations in cell apoptosis and levels of Dcx and reelin
      in the impairments of cerebellar development induced by developmental iodine
      deficiency and hypothyroidism.

PMID- 22595231
TI  - TCR stimulation upregulates MS4a4B expression through induction of AP-1
      transcription factor during T cell activation.
AB  - MS4a4B is a novel member of the membrane-spanning 4-domain family, subfamily A
      (MS4A) specifically expressed in mouse T cells. We have shown previously that
      expression of MS4a4B in T cells is upregulated upon T cell activation, suggesting
      that MS4a4B may play a functional role in regulation of T cell responses.
      However, little is known about the mechanisms that regulate MS4a4B gene
      expression. In this study, we explored the potential mechanism underlying TCR
      stimulation-induced expression of MS4a4B by promoter analysis. We cloned 2495bp
      of 5'-flanking region upstream of the MS4a4B start code and inserted the DNA
      fragment into pGL4.20 reporter plasmid. To analyze promoter activity of the
      cloned DNA fragment, we transiently transfected EL4 thymoma cells and the T32
      cell line with reporter plasmids. Expression of reporter gene was determined by
      dual-luciferase assay. Potential activator- and repressor-binding sites were
      analyzed by serial length of 5'-deletion. We have identified at least two
      potential activator binding regions and two potential repressor binding regions.
      The activator binding sites have been localized to two fragments, which are a 442
      base pair region (region A) positioned from -1176 to -735, and a 119-base pair
      region (region B) positioned -188 to -70 respectively. MatInspector analysis
      showed that region A contains the consensus binding motif of the AP-1 family of
      transcription factors. Machinery analysis showed that nuclear proteins extracted
      from anti-CD3/anti-CD28-activated primary T cells specifically bind to the AP-1
      binding element. In contrast, blockade by AP-1 inhibitor in culture decreased
      MS4a4B expression in T cells. Our data demonstrate that TCR-stimulation induces
      transactivation of AP-1 transcription factor, which subsequently binds to the
      MS4a4B promoter and upregulates expression of MS4a4B in activated T cells.

PMID- 22595233
TI  - Serum total bilirubin concentration is inversely correlated with Framingham risk
      score in Koreans.
AB  - BACKGROUND AND AIMS: Compelling evidence suggests that bilirubin, via its
      antioxidant potential, has anti-atherogenic properties, and that serum bilirubin
      concentrations within the reference range for the general population may provide
      some protection against coronary artery disease (CAD). This study examined the
      association between serum total bilirubin concentration and Framingham risk score
      (FRS) in the Korean population. METHODS: This cross-sectional study was performed
      on 19,792 Koreans. In addition to FRS, data on body mass index, fasting blood
      glucose, liver enzymes, lipid profile, uric acid, gamma glutamyltransferase, high
      sensitive C-reactive protein and total bilirubin were used. RESULTS: Negative
      correlations were established between log-transformed total bilirubin
      concentration and FRS (females; r = -0.067, p <0.001, males; r = -0.128, p
      <0.001). Analyses relating total bilirubin to FRS >=10% utilized multiple
      confounder adjusted logistic regression. Unadjusted odd ratios for FRS >=10% were
      0.325 (95% CI: 0.160-0.659, p = 0.002) and 0.342 (95% CI: 0.281-0.417, p <0.001)
      for log-transformed total bilirubin in females and males, respectively. These
      inverse relationships remained significant after adjustments for multiple
      confounders in both genders. CONCLUSIONS: Increased total bilirubin
      concentrations are associated with the decrease in FRS. Serum total bilirubin may
      be helpful to decrease the future risk of CAD.

PMID- 22595234
TI  - Normal variations in the morphology of auditory brainstem response (ABR)
      waveforms: a study in Wistar rats.
AB  - Auditory brainstem evoked responses (ABR) have been used for decades to assess
      auditory function. Surprisingly, despite the fact that rats are one of the most
      widely used experimental models in hearing, there have been no studies that have
      characterized in detail the normal morphological variations that occur in ABR
      waves. Therefore, the goal of this study was to characterize the patterns of ABR
      waves in rats to establish baseline criteria that could be used to identify
      abnormalities. Rats were stimulated with pure tone sounds at different
      frequencies and ABR waves were classified based on morphology. The most
      definitive finding was that, unlike what is observed in human ABRs, wave II of
      the rat ABR was the most prominent. Additionally, wave III was the smallest and,
      in many cases, was not apparent at low frequencies. Wave III was frequently
      involved in the formation of complexes, often appearing as a small wave or
      adjoining primarily wave IV. Complexes were common at low and medium frequencies
      and rare at high frequencies. These results indicate that knowledge of the
      different wave patterns in normal rats is fundamental to understanding how the
      wave morphology changes in pathological conditions that could lead to hearing
      impairment.

PMID- 22595235
TI  - Merlin, a multi-suppressor from cell membrane to the nucleus.
AB  - Recent evidence suggests that the neurofibromatosis type 2 (NF2) gene encoded
      protein merlin suppresses mitogenic signalling not only at the cell membrane but
      also in the nucleus. At the membrane, merlin inhibits signalling by integrins and
      tyrosine receptor kinases (RTKs) and the activation of downstream pathways,
      including the Ras/Raf/MEK/ERK, FAK/Src, PI3K/AKT, Rac/PAK/JNK, mTORC1, and
      Wnt/beta-catenin pathways. In the nucleus, merlin suppresses the E3 ubiquitin
      ligase CRL4(DCAF1) to inhibit proliferation. Gene expression analysis suggested
      that CRL4(DCAF1) could also regulate the expression of integrins and RTKs. In
      this review, we explore the links between merlin function at the membrane and in
      the nucleus, and discuss the potential of targeting the master regulator CRL4
      (DCAF1) to treat NF2 and other merlin-deficient tumours.

PMID- 22595236
TI  - Predicting protein function by multi-label correlated semi-supervised learning.
AB  - Assigning biological functions to uncharacterized proteins is a fundamental
      problem in the postgenomic era. The increasing availability of large amounts of
      data on protein-protein interactions (PPIs) has led to the emergence of a
      considerable number of computational methods for determining protein function in
      the context of a network. These algorithms, however, treat each functional class
      in isolation and thereby often suffer from the difficulty of the scarcity of
      labeled data. In reality, different functional classes are naturally dependent on
      one another. We propose a new algorithm, Multi-label Correlated Semi-supervised
      Learning (MCSL), to incorporate the intrinsic correlations among functional
      classes into protein function prediction by leveraging the relationships provided
      by the PPI network and the functional class network. The guiding intuition is
      that the classification function should be sufficiently smooth on subgraphs where
      the respective topologies of these two networks are a good match. We encode this
      intuition as regularized learning with intraclass and interclass consistency,
      which can be understood as an extension of the graph-based learning with local
      and global consistency (LGC) method. Cross validation on the yeast proteome
      illustrates that MCSL consistently outperforms several state-of-the-art methods.
      Most notably, it effectively overcomes the problem associated with scarcity of
      label data. The supplementary files are freely available at
      http://sites.google.com/site/csaijiang/MCSL.

PMID- 22595237
TI  - Hash subgraph pairwise kernel for protein-protein interaction extraction.
AB  - Extracting protein-protein interaction (PPI) from biomedical literature is an
      important task in biomedical text mining (BioTM). In this paper, we propose a
      hash subgraph pairwise (HSP) kernel-based approach for this task. The key to the
      novel kernel is to use the hierarchical hash labels to express the structural
      information of subgraphs in a linear time. We apply the graph kernel to compute
      dependency graphs representing the sentence structure for protein-protein
      interaction extraction task, which can efficiently make use of full graph
      structural information, and particularly capture the contiguous topological and
      label information ignored before. We evaluate the proposed approach on five
      publicly available PPI corpora. The experimental results show that our approach
      significantly outperforms all-path kernel approach on all five corpora and
      achieves state-of-the-art performance.

PMID- 22595238
TI  - Prognostic factors for recovery in chronic nonspecific low back pain: a
      systematic review.
AB  - BACKGROUND: Few data are available on predictors for a favorable outcome in
      patients with chronic nonspecific low back pain (CNLBP). PURPOSE: The aim of this
      study was to assess prognostic factors for pain intensity, disability, return to
      work, quality of life, and global perceived effect in patients with CNLBP at
      short-term (<= 6 months) and long-term (>6 months) follow-up. DATA SOURCES:
      Relevant studies evaluating the prognosis of CNLBP were searched in PubMed,
      CINAHL, and EMBASE (through March 2010). Study Selection Articles with all types
      of study designs were included. Inclusion criteria were: participants were
      patients with CNLBP (>= 12 weeks' duration), participants were older than 18
      years of age, and the study was related to prognostic factors for recovery.
      Fourteen studies met the inclusion criteria. DATA EXTRACTION: Two reviewers
      extracted the data and details of each study. DATA SYNTHESIS: A qualitative
      analysis using "level of evidence" was performed for all included studies. Data
      were summarized in tables and critically appraised. LIMITATIONS: The results of
      the studies reviewed were limited by their methodological weaknesses.
      CONCLUSIONS: At short-term follow-up, no association was found for the factors of
      age and sex with the outcomes of pain intensity and disability. At long-term
      follow-up, smoking had the same result. At long-term follow-up, pain intensity
      and fear of movement had no association with disability. At short-term follow-up,
      conflicting evidence was found for the association between the outcomes pain
      intensity and disability and the factor of fear of movement. At long-term follow
      up, conflicting evidence was found for the factors of age, sex, and physical job
      demands. At long-term follow-up, conflicting evidence also was found for the
      association between return to work and age, sex, and activities of daily living.
      At baseline, there was limited evidence of a positive influence of lower pain
      intensity and physical job demands on return to work. No high-quality studies
      were found for the outcomes of quality of life and global perceived effect.

PMID- 22595239
TI  - Lower-extremity force decrements identify early mobility decline among community
      dwelling older adults.
AB  - BACKGROUND: Many apparently independent older adults modify daily tasks. Task
      modifications strongly predict future mobility disability. Clinically intuitive,
      easily measured "biomarkers" associated with task modifications would offer
      quantifiable treatment targets for prevention of age-related functional
      limitations. OBJECTIVE: The objective of the study was to examine lower-extremity
      muscle strength deficits and functionally relevant cutoff points associated with
      daily task modifications in community dwelling older adults living independently.
      DESIGN: This was a cross-sectional observational study. METHODS: Fifty-three
      participants (mean age=76.4 years, SD=5.2) were tested for task modifications and
      leg strength. Task modifications were assessed using a previously described tool
      (summary task modification score). Twenty-six of the participants were classified
      as task modifiers (TM group), and 27 participants were classified as non-task
      modifiers (NTM group). A net antigravity leg force in the sagittal plane
      (NETforce) was calculated by summing the normalized isometric and isokinetic
      torques from the hip extensors, knee extensors, and ankle plantar flexors.
      RESULTS: Compared with the NTM group, the TM group exhibited 30.0% and 33.5%
      reduction in lower-extremity isometric and isokinetic NETforces, respectively.
      Isometric and isokinetic NETforce cutoff points for task modifications were <=
      4.24 and 2.77 N . m/kg body weight, respectively. The isometric and isokinetic
      models both yielded sensitivity and specificity values of 74.1% and 80.8%,
      respectively (positive likelihood ratio=3.852, 95% confidence interval=1.699
      8.735; negative likelihood ratio=0.321, 95% confidence interval=0.167-0.618).
      Isometric and isokinetic NETforces were significantly associated with task
      modifications (odds ratio=2.50 and 2.42, respectively). LIMITATIONS: The cross
      sectional design of this study does not allow for a test of causal relationships.
      This study used a modest yet adequate sample size that may limit generalization
      of the results. CONCLUSIONS: Isometric and isokinetic NETforce cutoff points
      provide quantifiable biomarkers that discriminate community-dwelling older adults
      who modify daily tasks from those who do not.

PMID- 22595240
TI  - The contribution of the Y chromosome to hybrid male sterility in house mice.
AB  - Hybrid sterility in the heterogametic sex is a common feature of speciation in
      animals. In house mice, the contribution of the Mus musculus musculus X
      chromosome to hybrid male sterility is large. It is not known, however, whether
      F1 male sterility is caused by X-Y or X-autosome incompatibilities or a
      combination of both. We investigated the contribution of the M. musculus
      domesticus Y chromosome to hybrid male sterility in a cross between wild-derived
      strains in which males with a M. m. musculus X chromosome and M. m. domesticus Y
      chromosome are partially sterile, while males from the reciprocal cross are
      reproductively normal. We used eight X introgression lines to combine different X
      chromosome genotypes with different Y chromosomes on an F1 autosomal background,
      and we measured a suite of male reproductive traits. Reproductive deficits were
      observed in most F1 males, regardless of Y chromosome genotype. Nonetheless, we
      found evidence for a negative interaction between the M. m. domesticus Y and an
      interval on the M. m. musculus X that resulted in abnormal sperm morphology.
      Therefore, although F1 male sterility appears to be caused mainly by X-autosome
      incompatibilities, X-Y incompatibilities contribute to some aspects of sterility.

PMID- 22595242
TI  - A coalescent model for genotype imputation.
AB  - The potential for imputed genotypes to enhance an analysis of genetic data
      depends largely on the accuracy of imputation, which in turn depends on
      properties of the reference panel of template haplotypes used to perform the
      imputation. To provide a basis for exploring how properties of the reference
      panel affect imputation accuracy theoretically rather than with computationally
      intensive imputation experiments, we introduce a coalescent model that considers
      imputation accuracy in terms of population-genetic parameters. Our model allows
      us to investigate sampling designs in the frequently occurring scenario in which
      imputation targets and templates are sampled from different populations. In
      particular, we derive expressions for expected imputation accuracy as a function
      of reference panel size and divergence time between the reference and target
      populations. We find that a modestly sized "internal" reference panel from the
      same population as a target haplotype yields, on average, greater imputation
      accuracy than a larger "external" panel from a different population, even if the
      divergence time between the two populations is small. The improvement in accuracy
      for the internal panel increases with increasing divergence time between the
      target and reference populations. Thus, in humans, our model predicts that
      imputation accuracy can be improved by generating small population-specific
      custom reference panels to augment existing collections such as those of the
      HapMap or 1000 Genomes Projects. Our approach can be extended to understand
      additional factors that affect imputation accuracy in complex population-genetic
      settings, and the results can ultimately facilitate improvements in imputation
      study designs.

PMID- 22595241
TI  - The Paf1 complex subunit Rtf1 buffers cells against the toxic effects of [PSI+]
      and defects in Rkr1-dependent protein quality control in Saccharomyces
      cerevisiae.
AB  - The Rtf1 subunit of the Paf1 complex is required for specific histone
      modifications, including histone H2B lysine 123 monoubiquitylation. In
      Saccharomyces cerevisiae, deletion of RTF1 is lethal in the absence of Rkr1, a
      ubiquitin-protein ligase involved in the destruction of nonstop proteins, which
      arise from mRNAs lacking stop codons or translational readthrough into the
      poly(A) tail. We performed a transposon-based mutagenesis screen to identify
      suppressors of rtf1Delta rkr1Delta lethality and found that a mutation in the
      gene encoding the protein chaperone Hsp104 rescued viability. Hsp104 plays a role
      in prion propagation, including the maintenance of [PSI+], which contributes to
      the synthesis of nonstop proteins. We demonstrate that rtf1Delta and rkr1Delta
      are synthetically lethal only in the presence of [PSI+]. The deletion,
      inactivation, and overexpression of HSP104 or the overexpression of prion
      encoding genes URE2 and LSM4 clear [PSI+] and rescue rtf1Delta rkr1Delta
      lethality. In addition, the presence of [PSI+] decreases the fitness of rkr1Delta
      strains. We investigated whether the loss of RTF1 exacerbates an overload in
      nonstop proteins in rkr1Delta [PSI+] strains but, using reporter plasmids, found
      that rtf1Delta decreases nonstop protein levels, indicating that excess nonstop
      proteins may not be the cause of synthetic lethality. Instead, our data suggest
      that the loss of Rtf1-dependent histone modifications increases the burden on
      quality control pathways in cells lacking Rkr1 and containing [PSI+].

PMID- 22595243
TI  - The mRNA decay pathway regulates the expression of the Flo11 adhesin and biofilm
      formation in Saccharomyces cerevisiae.
AB  - Regulation of the FLO11 adhesin is a model for gene expression control by
      extracellular signals and developmental switches. We establish that the major
      mRNA decay pathway regulates FLO11 expression. mRNA deadenylation of
      transcriptional repressors of FLO11 by the exonuclease Ccr4 keeps their levels
      low, thereby allowing FLO11 transcription.

PMID- 22595245
TI  - Asexuals, polyploids, evolutionary opportunists...: the population genetics of
      positive but deteriorating mutations.
AB  - Some genetic phenomena originate as mutations that are initially advantageous but
      decline in fitness until they become distinctly deleterious. Here I give the
      condition for a mutation-selection balance to form and describe some of the
      properties of the resulting equilibrium population. A characterization is also
      given of the fixation probabilities for such mutations.

PMID- 22595244
TI  - New negative feedback regulators of Egfr signaling in Drosophila.
AB  - The highly conserved epidermal growth factor receptor (Egfr) pathway is required
      in all animals for normal development and homeostasis; consequently, aberrant
      Egfr signaling is implicated in a number of diseases. Genetic analysis of
      Drosophila melanogaster Egfr has contributed significantly to understanding this
      conserved pathway and led to the discovery of new components and targets. Here we
      used microarray analysis of third instar wing discs, in which Egfr signaling was
      perturbed, to identify new Egfr-responsive genes. Upregulated transcripts
      included five known targets, suggesting the approach was valid. We investigated
      the function of 29 previously uncharacterized genes, which had pronounced
      responses. The Egfr pathway is important for wing-vein patterning and using
      reverse genetic analysis we identified five genes that showed venation defects.
      Three of these genes are expressed in vein primordia and all showed
      transcriptional changes in response to altered Egfr activity consistent with
      being targets of the pathway. Genetic interactions with Egfr further linked two
      of the genes, Sulfated (Sulf1), an endosulfatase gene, and CG4096, an A
      Disintegrin And Metalloproteinase with ThromboSpondin motifs (ADAMTS) gene, to
      the pathway. Sulf1 showed a strong genetic interaction with the neuregulin-like
      ligand vein (vn) and may influence binding of Vn to heparan-sulfated
      proteoglycans (HSPGs). How Drosophila Egfr activity is modulated by CG4096 is
      unknown, but interestingly vertebrate EGF ligands are regulated by a related
      ADAMTS protein. We suggest Sulf1 and CG4096 are negative feedback regulators of
      Egfr signaling that function in the extracellular space to influence ligand
      activity.

PMID- 22595246
TI  - Effect of surgeon's caseload on the quality of surgery and breast cancer
      recurrence.
AB  - The aim of this study was to evaluate the effects of the caseloads of individual
      surgeons on breast cancer primary care and outcome. The extent of primary breast
      cancer and axillary surgery and the appearance of local recurrences were
      evaluated for 1377 women operated in Pirkanmaa region between 1.1.1997 and
      31.12.2001 and followed- up at least until 31.12.2008 or death. Caseloads of each
      surgeon were divided into three categories: over 550, 100-200 and under 60.
      Breast conserving surgery was performed more often by surgeons with the highest
      (OR 1.32) and the middle (OR 1.54) caseload volumes compared to those with the
      lowest volumes (p = 0.018). Surgeons with the lowest caseloads also dissected
      fewer lymph nodes (mean 9.4 versus 11.2 in the highest and 10.9 in the middle
      caseload volumes; p <= 0.001). There were no differences in recurrences between
      the groups during the mean follow-up time of 8.9 years.

PMID- 22595247
TI  - Breast reconstruction following mastectomy for invasive breast cancer is strongly
      influenced by demographic factors in women in Victoria, Australia.
AB  - This study explored factors associated with the likelihood of reconstruction
      after unilateral mastectomy and the wellbeing of women after reconstruction. Data
      were from a questionnaire completed on average 1.8 years after diagnosis by 1429
      women in the BUPA Health and Wellbeing After Breast Cancer Study. Logistic
      regression was used to model factors associated with reconstruction. The
      Psychological General Wellbeing Questionnaire was used to assess wellbeing. A
      total of 25.4% of 366 women who had a unilateral mastectomy had undergone a
      reconstruction nearly two years after diagnosis. Being younger (p<0.001),
      educated beyond school (p<0.04), living in the metropolitan area (p<0.001),
      having private health insurance (p=0.003), not having dependent children
      (p=0.004) and not having radiotherapy (p<0.001) explained just over 40% of the
      variation in reconstruction status. There was a modest difference between women
      who did and did not have a reconstruction in terms of wellbeing. Demographic
      factors strongly influence the likelihood of reconstruction after mastectomy.

PMID- 22595248
TI  - The impact of immediate breast reconstruction on post-mastectomy lymphedema in
      patients undergoing modified radical mastectomy.
AB  - The aim of this study was to assess the impact of immediate breast reconstruction
      (IBR) with autologous tissue on the development of post-mastectomy lymphedema in
      patients undergoing modified radical mastectomy (MRM). A retrospective chart
      review was performed for early-stage breast cancer patients who underwent MRM
      between January 2001 and December 2009. Patients were categorized into two groups
      based on whether or not they underwent IBR. The incidence of lymphedema was
      assessed and compared. A total of 712 patients underwent MRM, which included 117
      patients undergoing IRB. There were no significant differences between two groups
      except for a lower body mass index in the reconstruction group. Comparing the
      incidence of lymphedema using multivariate logistic regression analysis, the
      reconstruction group had a significantly lower incidence of lymphedema (p-value =
      0.023). Breast cancer patients who underwent MRM with IBR had a significantly
      lower incidence of lymphedema than those in the non-reconstruction group.

PMID- 22595249
TI  - Synthesis, spectral studies and antimicrobial activities of some 2-naphthyl
      pyrazoline derivatives.
AB  - A series of 2-naphthyl pyrazolines were synthesized by the cyclization of 2
      naphthyl chalcones and phenylhydrazine hydrochloride in the presence of sodium
      acetate. The yields of pyrazoline derivatives are more than 80%. The synthesized
      pyrazolines were characterized by their physical constants, IR, (1)H, (13)C and
      MS spectra. From the IR and NMR spectra the C=N (cm(-1)) stretches, the
      pyrazoline ring proton chemical shifts (ppm) of delta(Ha), H(b) and H(c) and also
      the carbon chemical shifts (ppm) of deltaC=N are correlated with Hammett
      substituent constants, F and R, and Swain-Lupton's parameters using single and
      multi-regression analyses. From the results of linear regression analysis, the
      effect of substituents on the group frequencies has been predicted. The
      antimicrobial activities of all synthesized pyrazolines have been studied.

PMID- 22595250
TI  - Phase transformation and disorder effect on optical and electrical properties of
      Zn3P2 thin films.
AB  - The phase transformation of zinc phosphide (Zn(3)P(2)) thin films was detected
      through isochronal annealing process. The effects on isochronal annealing on the
      internal structural, optical and electrical properties of deposited Zn(3)P(2)
      thin films have been discussed. The films were prepared by thermal evaporation
      under constant preparation conditions of vacuum 1.3*10(-5)Torr, substrate
      temperature (300K), rate of deposition (~1nm/s) and film thickness (480nm). The
      annealing process was carried out under vacuum for 2h at different temperatures
      ranging from 373 to 623K. X-ray diffraction patterns showed that the as-deposited
      films and those annealed at temperatures less than 623K exhibit amorphous
      structure, while the films annealed at 623K showed tetragonal polycrystalline
      structure. The optical transmission and reflection spectra were measured at the
      wavelength range of 190-2500nm. The absorption coefficient spectra and the degree
      of disorder as measured from the absorption edge were determined. The indirect
      and direct optical energy band gaps were evaluated for indirect allowed and
      direct allowed transitions for amorphous and polycrystalline films, respectively.
      The refractive index n(o) increases with raising the annealing temperature which
      refers to more condensation in the material. The electrical resistivity for
      Zn(3)P(2) films decreases exponentially with raising the annealing temperature up
      to 623K as influenced by structure transformation and decreasing the degree of
      disorder in the films.

PMID- 22595251
TI  - Effect of temperature on the spectral characteristics of 2-(4'-N,N
      dimethylaminophenyl)imidazo[4,5-b]pyridine.
AB  - The photophysical behaviors of 2-(4'-N,N-dimethylaminophenyl)imidazo[4,5
      b]pyridine (DMAPIP-b) were studied as a function of temperature in six different
      solvents (cyclohexane, acetonitrile, ethanol, methanol, 1-proponal and glycerol),
      using absorption, steady-state emission and time-resolved fluorescence
      techniques. The temperature strongly affects the fluorescence quantum yields and
      life times of both TICT and normal emissions of DMAPIP-b. Density functional
      theory (DFT) calculations have been performed on all two isomers of DMAPIP-b.
      Solvent stabilization effects have also been studied based on integral equation
      formalism-polarizable continuum (IEF-PCM) model in four different solvents,
      cyclohexane, acetonitrile, ethanol and methanol. The calculations suggested that
      isomer I is more stable than isomer II of all these solvents. Both solvatochromic
      and thermochromic methods were used to calculate the dipole moment of the TICT
      state and the values obtained by both methods are in good agreement with each
      other.

PMID- 22595252
TI  - Synthesis and characterization of highly conductive charge-transfer complexes
      using positron annihilation spectroscopy.
AB  - Molecular charge-transfer complexes of the tetramethylethylenediamine (TMEDA)
      with picric acid (Pi-OH), benzene-1,4-diol (QL), tin(IV) tetrachloride (SnCl(4)),
      iodine, bromine, and zinc chloride (ZnCl(2)) have been synthesized and
      investigated by elemental and thermal analysis, electronic, infrared, Raman and
      proton-NMR, energy-dispersive X-ray spectroscopy, X-ray powder diffraction and
      positron annihilation lifetime spectroscopy, and scanning electron microscopy. In
      this work, three types of acceptors pi-acceptors (Pi-OH and QL), sigma-acceptors
      (iodine and bromine), and vacant orbital acceptors (SnCl(4) and ZnCl(2)) were
      covered. The results of elemental analysis indicated that the CT complexes were
      formed with ratios 1:1 and 1:2 for QL, SnCl(4), and ZnCl(2) acceptors and iodine,
      Pi-OH, and Br(2) acceptors, respectively. The type of chelating between the TMEDA
      donor and the mentioned acceptors depends upon the behavior of both items. The
      positron annihilation lifetime parameters were found to be dependent on the
      structure, electronic configuration, and the power of acceptors. The correlation
      between these parameters and the molecular weight and biological activities of
      studied complexes was also observed. Regarding the electrical properties, the AC
      conductivity and the dielectric coefficients were measured as a function of
      frequency at room temperature. The TMEDA charge-transfer complexes were screened
      against antibacterial (Escherichia coli, Staphylococcus aureus, Bacillus
      subtilis, and Pseudomonas aeruginosa) and antifungal (Aspergillus flavus and
      Candida albicans) activities.

PMID- 22595253
TI  - [Correlation between toe-brachial index and ankle-brachial index in patients with
      diabetes mellitus type 2].
AB  - BACKGROUND AND OBJECTIVE: We aimed to know the prevalence of abnormal toe
      brachial index (TBI) in a group of patients with type 2 diabetes mellitus (DM2).
      We also aimed to know the correlation between TBI and the ankle-brachial index
      (ABI) in these patients and determine the abnormal value of TBI. PATIENTS AND
      METHODS: Descriptive cross-sectional study conducted in primary care. DM2
      patients over 50 years were included. Systolic blood pressure at the arm, ankle
      and toe were determined to calculate the ABI and the TBI. RESULTS: We studied 175
      patients (350 limbs) of a mean age of 67 years (SD=9), 53.7% were women and 72.3%
      had hypertension. The ABI was abnormal (<= 0.90) in 8.3% of the limbs and 8.6%
      met criteria of calcification (>= 1.40). The TBI was abnormal (<= 0.60) in 18.6%
      of cases. Of the 291 limbs with a normal ABI, 34 (11.7%) had an abnormal value of
      TBI and the 30 limbs with a calcified ABI, 6 (20%) had an abnormal value of TBI.
      There was a positive linear correlation between ABI and TBI (r = 0.395, P <
      .001). CONCLUSIONS: Determination of TBI provides additional information to ABI
      determination and exploration can be very useful in cases of arterial
      calcification. The value <= 0.60 is the best one to consider an abnormal TBI.

PMID- 22595254
TI  - [Confidentiality in electronic medical records in hospital mental health].

PMID- 22595255
TI  - Arthroscopic repair of large and massive rotator cuff tears using the side-to
      side suture technique. Mid-term clinical and anatomic evaluation.
AB  - PREAMBLE: Arthroscopic repair is our treatment of choice for massive rotator cuff
      tears. In order to reduce tension, we perform a side-to-side suture technique.
      The purpose of our work was to study the outcome of such technique by evaluating
      functional score and rotator cuff integrity using ultrasound at 2-year follow-up.
      HYPOTHESIS: The "side-to-side" arthroscopic repair of large and massive rotator
      cuff tears provides a long-term continuity of rotator cuff mechanism, enhances
      function and relieves pain with low morbidity. TYPE OF STUDY: Retrospective
      monocenter study. MATERIAL AND METHODS: We included a continuous series of 50
      patients of mean age 66.6 years (46-80), operated on between January 2007 and
      March 2008 for full-thickness retracted tears of the supraspinatus extending or
      not to the infraspinatus tendon. Management consisted of arthroscopic subacromial
      bursectomy, acromioplasty and side-to-side repair of the rotator cuff tendons
      with secure anchor fixation to the tuberosity. The relative Constant score was
      used for clinical evaluation preoperatively and at a minimum of 24 months after
      surgery. The continuity of rotator cuff mechanism was evaluated using ultrasound.
      RESULTS: The mean relative Constant score improved significantly (p<0.05) from
      40% (18-67) preoperatively to 91.7% (40-107) postoperatively. Fifty-six percent
      of the rotator cuffs from this series demonstrated continuity with a
      postoperative relative Constant score of 98.4% (74-121) and an increase in the
      shoulder strength score of 3.6 kg (1-6). Forty-four percent of the rotator cuffs
      had recurrent tear with an overall relative Constant score of 83.6% (4-126) and
      we did not observe any improvement in the strength score in this sub-group.
      Eighty-eight percent of the patients were satisfied or very satisfied with their
      outcome. DISCUSSION: At a minimum 24-month follow-up, the side-to-side suturing
      technique reported excellent functional results with a very high satisfaction
      rate. For these large and massive rotator cuff tears sometimes considered as
      irreparable, ultrasound confirmed the continuity of the repair in 56% of the
      cases. Unhealed patients were not disadvantaged since they experienced pain
      relief and functional improvement. However, in this sub-group of patients,
      recovery of shoulder strength was poor. LEVEL OF EVIDENCE: Level IV.

PMID- 22595257
TI  - Total ankle arthroplasty - total ankle arthroplasty in Western France: influence
      of volume on complications and clinical outcome.
AB  - INTRODUCTION: Total ankle arthroplasty (TAA) has become an alternative to ankle
      arthrodesis in the treatment of advanced osteoarthritis. "The difficulty of
      performing a total ankle replacement and the corresponding steep learning curve"
      has resulted in a proposal "to limit ankle replacement to centers that have
      performed at least ten total ankle replacements for at least 3 years". The aim of
      this study was to evaluate the influence of the frequency of TAA procedures on
      the complications and outcome of these arthroplasties. MATERIALS AND METHODS:
      This retrospective series included 183 cases who underwent surgery between 1997
      2010 in eight centers: three high volume centers performed at least five TAA per
      year (100 cases) and six low volume centers performed less than five TAA per year
      (78 cases). RESULTS: The clinical assessment was performed in 133 cases that were
      reviewed after a mean 39 months +/- 29 of follow-up. The preoperative AOFAS score
      was 33 +/- 4 and 77 +/- 15 at the final follow-up. The five-year survival rate
      was 86%. No significant difference was found between the groups for the AOFAS
      score or implant survival at the final follow-up. The high volume centers
      experienced more complications (45% versus 13%) but fewer implant failures (8%
      versus 13%) overall compared to the low volume centers. DISCUSSION: The outcome
      of TAA depends mainly upon the pertinence of the indication and the associated
      procedures that may be necessary. Rather than limiting TAA to high volume
      reference centers, we suggest that the assessment of each case within a
      predetermined area should be done in a network. This would determine the degree
      of specialization required for each TAA case and provide all patients with safe
      and equal access to this therapeutic option. LEVEL OF EVIDENCE: IV -
      Retrospective study.

PMID- 22595256
TI  - Total ankle arthroplasty - three-component total ankle arthroplasty in western
      France: a radiographic study.
AB  - INTRODUCTION: Although the literature has confirmed the short and intermediate
      term efficacy of three-component mobile-bearing total ankle arthroplasty (TAA),
      the development of progressive periprosthetic bone abnormalities threatens the
      intermediate and long term survival of these implants. The aim of this study was
      to evaluate whether TAA quality requirements were met and analyze radiological
      changes in arthroplasties performed by members of the French Western Orthopedics
      Society. MATERIALS AND METHODS: This retrospective multicenter study included 173
      patients who underwent three-component mobile-bearing arthroplasty between 1997
      and 2010 in eight centers in western France. The etiology was osteoarthritis (OA)
      in 78% of cases and rheumatoid arthropathy in 13% of cases. The radiographic
      assessment included preoperative and final postoperative standing anteroposterior
      (AP) and lateral view radiographs. Radiographs were reviewed for ankle alignment,
      improper implant positions, and periprosthetic bone anomalies. Intraprosthetic
      range of motion was evaluated in 111 cases on dynamic radiographs. RESULTS: Mean
      follow-up was 34 months (+/- 5). Fifteen percent of the cases presented implant
      malposition. Alignment was normal in 76% of cases. Intraprosthetic range of
      motion was 20.5 degrees  (+/- 3) in the cases that were evaluated. Bone cysts
      were observed in 33% of cases, radioluncencies in 72%, ossifications in 39%,
      migration of the tibial component in 5% and migration of the talar component in
      27%. The latter were correlated to a range of motion of less than 15 degrees .
      Additional surgery was necessary in 8% of cases to revise implants and/or for
      conversion to arthrodesis. DISCUSSION: The high rate of radiolucencies and bone
      cysts at a mean follow-up of 2.8 years is of concern and these arthroplasties
      should be closely monitored. Stiff ankles seemed to be at a higher risk for
      subsidence. LEVEL OF EVIDENCE: IV - Retrospective study.

PMID- 22595258
TI  - Critical study of resection margins in adult soft-tissue sarcoma surgery.
AB  - INTRODUCTION: Resection margins constitute a recognized risk factor for local
      recurrence, but their impact on survival is less clear. HYPOTHESIS: Infiltrative
      proliferation and satellite nodules are prognostic factors for local and systemic
      aggressiveness. TYPE OF STUDY: Retrospective cohort study. PATIENTS AND METHODS:
      In 105 patients under curative treatment, resection quality was assessed on UICC
      criteria (R0/R1) and on a modified version (R0M/R1M) taking account of
      proliferation contours and satellite nodules for narrow margins (<1mm). Uni- and
      multi-variate analysis was performed, and Kaplan-Meier survival curves were
      compared on log-rank. RESULTS: Mean 5-year local recurrence-free survival (LRFS)
      was 0.64 [0.52-0.76] after R1 surgery, 0.9 [0.85-0.95] after R0, 0.64 [0.519
      0.751] after R1M and 0.92 [0.87-0.96] after R0M. Resection type according to R
      classification correlated with disease-free survival (DFS) (P=0.028), but not
      with metastasis-free survival (MFS) (P=0.156). Resection type according to RM
      classification correlated with DFS and MFS. Multivariate analysis disclosed
      correlations between LRFS rate and RM resection type (HR 6.77 [1.78-25.7],
      P=0.005), DFS rate and RM resection type (HR 2.83 [1.47-5.43], P=0.001) and grade
      (HR=3.17 [1.38-7.27], P=0.003), and MFS and grade (HR=3.96 [1.50-10.5], P=0.006).
      DISCUSSION: The microscopic aspect of the proliferation contours and presence of
      satellite nodules were confirmed as prognostic factors for local and systemic
      aggressiveness. They impact both disease-free survival and metastasis-free
      survival in case of margins less than 1mm. Their systematic consideration may
      help identify patients with elevated systemic risk. LEVEL OF EVIDENCE: IV.

PMID- 22595260
TI  - Characterization of Jamaican agro-industrial wastes. Part II, fatty acid
      profiling using HPLC: precolumn derivatization with phenacyl bromide.
AB  - This paper describes the determination of fatty acid composition of coffee,
      citrus and rum distillery wastes using reversed-phase high-performance liquid
      chromatography (RP-HPLC). Lipid extracts of the waste samples are derivatized
      with phenacyl bromide and their phenacyl esters are separated on a C8 reversed
      phase column by using continuous gradient elution with water and acetonitrile.
      The presence of saturated and unsaturated fatty acids in quantifiable amounts in
      the examined wastes, as well as the high percentage recoveries, are clear
      indications that these wastes have potential value as inexpensive sources of
      lipids. The HPLC procedures described here could be adopted for further analysis
      of materials of this nature.

PMID- 22595259
TI  - Development and validation of a stability-indicating method for determination of
      free sterols in the Asian medicinal leech Hirudo manillensis.
AB  - A rapid, simple, sensitive, selective, precise and robust thin-layer
      chromatography densitometric method for the determination of free sterols in
      leech was developed and validated on silica gel layer using carbon tetrachloride
      methanol-formic acid (9.5:1.5:0.55, v/v/v). Spectrodensitometric scanning was
      carried using a Camag TLC scanner III at 366 nm after spraying 2% methanolic
      sulphuric acid, which gave compact spots for cholesterol (R(F) = 0.35 +/- 0.02).
      The regression analysis data for calibration plot implied a good linear
      relationship (r(2) = 0.99958) between response and concentration over the range
      100-600 ng per spot with respect to peak area. The limits of detection and
      quantification were found to be 13.8 +/- 0.51 and 45.01 +/- 1.29 ng per spot,
      respectively. Validation was in accordance to the International Conference on
      Harmonization guidelines. Cholesterol was subjected to forced stress conditions
      of oxidation, hydrolysis and heat. Degradation products resulting from the forced
      stress did not interfere with detection because the degradant peaks were well
      separated from the cholesterol peak. The densitometric method can be regarded as
      stability-indicating and can be used for quality control assay of cholesterol in
      leech extract.

PMID- 22595261
TI  - Development and validation of a stability-indicating gas chromatographic method
      for quality control of residual solvents in blonanserin: a novel atypical
      antipsychotic agent.
AB  - Blonanserin is a novel atypical antipsychotic agent for the treatment of
      schizophrenia. Ethyl alcohol, isopropyl alcohol and toluene are utilized in the
      synthesis route of this bulk drug. A new validated gas chromatographic (GC)
      method for the simultaneous determination of residual solvents in blonanserin is
      described in this paper. Blonanserin was dissolved in N, N-dimethylformamide to
      make a sample solution that was directly injected into a DB-624 column. A postrun
      oven temperature at 240 degrees C for approximately 2 h after the analysis cycle
      was performed to wash out blonanserin residue in the GC column. Quantitation was
      performed by external standard analyses and the validation was carried out
      according to International Conference on Harmonization validation guidelines Q2A
      and Q2B. The method was shown to be specific (no interference in the blank
      solution), linear (correlation coefficients >=0.99998, n = 10), accurate (average
      recoveries between 94.1 and 101.7%), precise (intra-day and inter-day precision
      <=2.6%), sensitive (limit of detection <=0.2 ng, and limit of quantitation <=0.7
      ng), robust (small variations of carrier gas flow, initial oven temperature,
      temperature ramping rate, injector and detector temperatures did not
      significantly affect the system suitability test parameters and peak areas) and
      stable (reference standard and sample solutions were stable over 48 h). This
      extensively validated method is ready to be used for the quality control of
      blonanserin.

PMID- 22595262
TI  - New HPLC method to detect individual opioids (heroin and tramadol) and their
      metabolites in the blood of rats on combination treatment.
AB  - Drug abuse is both an age-old and a constantly evolving problem in society.
      Trends in illicit drug use are highly fluid, with new formulations increasing in
      popularity. For this reason, methods for illicit drug detection and analysis need
      to be continually updated so they remain useful and relevant. A recent trend in
      street heroin production has seen it diluted with large amounts of tramadol in
      addition to the classical diluents such as acetaminophen and caffeine. This study
      describes a sensitive, simple and accurate high-performance liquid
      chromatographic method with ultraviolet detection for the simultaneous detection
      of heroin, 6-acetylmorphine, morphine, tramadol and O-desmethyltramadol in the
      blood of rats using a liquid-liquid back-extraction method. The separation was
      performed on LichroCART RP-18e with particle size of 5 um (250 * 4.6 mm) with
      mobile phase acetonitrile-50 mM KH(2)PO(4) buffer, pH 7.1, using a gradient mode
      with a 1.0 mL/min flow rate. The calibration curves were linear in the
      concentration ranges 0.25-100 and 0.1-100 ug/mL for morphine and other analytes,
      respectively. Recovery values for the substances ranged between 59 and 83%. This
      technique was successfully used in pharmacokinetic studies measuring 6
      acetylmorphine, morphine, tramadol and O-desmethyltramadol in the blood of rats
      intraperitoneally treated with a blend of 10 mg/kg heroin and 70 mg/kg tramadol.
      This technique shows promise for analysis of confiscated street heroin.

PMID- 22595263
TI  - Effect of age on the pathogenesis and innate immune responses in Pekin ducks
      infected with different H5N1 highly pathogenic avian influenza viruses.
AB  - The pathogenicity of H5N1 highly pathogenic avian influenza (HPAI) viruses in
      domestic ducks varies between different viruses and is affected by the age of the
      ducks, with younger ducks presenting a more severe disease. In order to better
      understand the pathobiology of H5N1 HPAI in ducks including the role of host
      responses, 2 and 5-week-old Pekin ducks were infected with three different H5N1
      HPAI viruses. Virus-induced pathology ranged from no clinical signs to severe
      disease and mortality, with the 2-week-old ducks being more severely affected by
      the more virulent viruses. However, these more virulent viruses induced higher
      body temperatures in the 5-week-old ducks than in the 2-week-old ducks indicating
      possible differences in innate immune responses. To analyze the ducks host
      responses to H5N1 HPAI virus infection, expression of innate immune-related genes
      was measured in the spleens and lungs of infected ducks at the peak of virus
      infection. IFN-alpha, RIG-I, and IL-6 RNA levels were increased in spleens
      regardless of the virus given and the age of the ducks, however differences were
      observed in the levels of up-regulation of IFN-alpha and RIG-I between the 2 and
      the 5-week-old ducks with the more virulent virus. Differences in IL-2 gene
      expression were also observed. In the lungs, the levels of expression of innate
      immune-related genes were lower than in the spleen, with mostly up-regulation of
      RIG-I and IL-6 and down-regulation of IFN-alpha and IL-2; no significant
      difference in expression was found between the 2 and the 5-week-old ducks. The
      differences observed in the innate immune responses to infection with H5N1 HPAI
      viruses could explain in part the differences in pathogenicity found between the
      2 and 5-week-old ducks, however earlier time points after infection and
      additional innate immune-related genes should be examined.

PMID- 22595264
TI  - The O3-Vet project: integration of a standard nomenclature of clinical terms in a
      veterinary electronic medical record for veterinary hospitals.
AB  - In order to improve the hospital information system of the Chilean University
      Hospital, the Veterinary Medicine School of Universidad de Chile made a research
      cooperation with Universita San Raffaele Roma to develop and test a new release
      of the O3-Vet software application. O3-Vet was selected by the Chilean University
      mainly for two reasons: (1) it uses human medicine standardized technologies such
      as "Health Level 7" (HL7) and "Integrating the Healthcare Enterprise" (IHE),
      which allow a good level of data sharing and hospital management; (2) it is open
      source, which means it can be adapted to specific hospital needs. In the new
      release, a subset of diagnostic terms was added from the "Systematized
      Nomenclature of Medicine Clinical Terms" (SNOMED CT), selected by the "American
      Animal Hospital Association" (AAHA) to standardize the filing of clinical data
      and its retrieval. Results from a limited survey of veterinarians of the
      University (n=9) show that the new release improved the management of the Chilean
      University Hospital and the ability to retrieve useful clinical data.

PMID- 22595265
TI  - Adult immunization recommendations in the US--new changes and a plea for a global
      adult immunization schedule.

PMID- 22595267
TI  - Dr Mario Raviglione, director of the Stop TB Department World Health
      Organization. Interview by Christo Hall.
AB  - Tuberculosis (TB) is a very global disease; there are over 9 million new
      incidences of TB every year with the vast majority of cases emerging in the
      developing world. As one of three major diseases associated with poverty it
      affects the areas where poverty is most  prevalent, notably Asia and Africa.
      While the incidence rate has been slowly declining in the developed world it
      continues to pose a major health threat to even the most developed nations. To
      demonstrate the global, and persistent, nature of TB we asked Dr Mario
      Raviglione, Director of the  World Health Organization's Stop TB Department to
      provide an analysis on the current TB situation in the United Kingdom and comment
      on what measures should be taken to alleviate the issue of TB in one of the
      world's richest countries.

PMID- 22595268
TI  - Immigrant screening for TB: a missed opportunity to improve TB control in the
      United Kingdom.
AB  - Tuberculosis in the United Kingdom and other high-income countries is primarily a
      disease of the foreign-born arising from the synergy of migration from high TB
      burden regions and the reactivation of remotely acquired latent TB infection. UK
      immigrant screening policy primarily aims to identify active, rather than latent,
      TB although mounting evidence indicates that implementing latent TB screening for
      new entrants from intermediate and high incidence countries could cost
      effectively reduce TB incidence in the UK.

PMID- 22595269
TI  - High rate of Quantiferon positive and tuberculin negative tests in infants born
      at a large Italian university hospital in 2011: a cautionary hypothesis.
AB  - In the summer of 2011, an outbreak of Mycobacterium tuberculosis infection was
      suspected, and widely publicized, to have occurred in a maternity ward of an
      Italian University Hospital based on a case of tuberculosis in a nurse and
      another case in a newborn.  More than 1300 newborns in the Hospital were surveyed
      for the occurrence of latent TB by the use of interferon-gamma released assays,
      which was positive in 118 newborns, all negative at the tuberculin skin test. We
      present here several theoretical arguments and literature data suggesting caution
      in interpreting the interferon-gamma released assays positivity alone as
      indication of latent TB infection in newborns.

PMID- 22595270
TI  - Bovine lactoferrin-derived peptides as novel broad-spectrum inhibitors of
      influenza virus.
AB  - Bovine lactoferrin (bLf) is a multifunctional glycoprotein that plays an
      important role in innate immunity against infections, including influenza. Here
      we have dissected bLf into its C- and N-lobes and show that inhibition of
      influenza virus hemagglutination and  cell infection is entirely attributable to
      the C-lobe and that all major virus subtypes, including H1N1 and H3N2, are
      inhibited. By far-western blotting and sequencing studies, we demonstrate that
      bLf C-lobe strongly binds to the HA(2) region of viral hemagglutinin, precisely
      the  highly conserved region containing the fusion peptide. By molecular docking
      studies, three C-lobe fragments were identified which inhibited virus
      hemagglutination and infection at fentomolar concentration range. Besides
      contributing to explain the broad anti-influenza activity of bLf, our  findings
      lay the foundations for exploiting bLf fragments as source of potential anti
      influenza therapeutics.

PMID- 22595271
TI  - Infertility resulting from transgenic I-PpoI male Anopheles gambiae in large cage
      trials.
AB  - OBJECTIVES: Anopheles gambiae is the primary vector of malaria in sub-Saharan
      Africa and is a potential target of genetic control programs. We determined the
      capacity of male A. gambiae created by germline transformation to introduce
      infertility  into stable age-distribution populations. We also determined effects
      of the transgenes on life history. METHODS: Stable age-distribution populations
      of A. gambiae mosquitoes were established in large indoor cages. Male mosquitoes
      carrying an I-PpoI homing endonuclease gene  were introduced at *5 and *10
      release rates where they competed with target male mosquitoes for matings.
      Similar trials were conducted in small cages with an additional *1 release level.
      RESULTS: Infertility was successfully introduced into all target populations.  In
      supporting experiments, complete female infertility was observed in all strains
      and species of the A. gambiae complex to which transgenic males were mated. Life
      history experiments demonstrated that reductions in I-PpoI male vigor exist in
      the form of reduced adult male emergence,  longevity and competitiveness.
      DISCUSSION: A. gambiae I-PpoI males are capable of introducing high levels of
      infertility in target populations in indoor cage trials. This was accomplished
      despite losses of vigor resulting from the HEG transgene. These results motivate
      further  trials of sexually I-PpoI A. gambiae in outdoor cage and field trials.

PMID- 22595272
TI  - Quality and safety of integrated community case management of malaria using rapid
      diagnostic tests and pneumonia by community health workers.
AB  - OBJECTIVES: To assess the quality and safety of having community health workers
      (CHWs) in rural Zambia use rapid diagnostic tests (RDTs) and provide integrated
      management of malaria and pneumonia. DESIGN/METHODS: In the context of a cluster
      randomized  controlled trial of two models for community-based management of
      malaria and/or non-severe pneumonia in children under 5 years old, CHWs in the
      intervention arm were trained to use RDTs, follow a simple algorithm for
      classification and treat malaria with artemether-lumefantrine (AL)  and pneumonia
      with amoxicillin. CHW records were reviewed to assess the ability of the CHWs to
      appropriately classify and treat malaria and pneumonia, and account for supplies.
      Patients were also followed up to assess treatment safety. RESULTS: During the 12
      month study, the CHWs  evaluated 1017 children with fever and/or fast/difficult
      breathing and performed 975 RDTs. Malaria and/or pneumonia were appropriately
      classified 94-100% of the time. Treatment based on disease classification was
      correct in 94-100% of episodes. Supply management was excellent  with over 98% of
      RDTs, amoxicillin, and AL properly accounted for. The use of RDTs, amoxicillin,
      and AL was associated with few minor adverse events. Most febrile children (90%)
      with negative RDT results recovered after being treated with an antipyretic
      alone. CONCLUSIONS: Volunteer  CHWs in rural Zambia are capable of providing
      integrated management of malaria and pneumonia to children safely and at high
      quality.

PMID- 22595274
TI  - Retention and loss to follow-up in antiretroviral treatment programmes in
      southeast Nigeria.
AB  - BACKGROUND: This study generated new information about the outcomes of patients
      enrolled in antiretroviral treatment programmes, as well as the true outcomes of
      those lost to follow-up (LTF). METHODS: Anonymized data were collected for
      patients enrolled  over a 12-month period from two programmes (public and
      private) in southeast Nigeria. Estimates of retention, LTF, mortality and
      transfers were computed. All LTF enrollees (defined as patients who had missed
      three scheduled visits) whose contact information met pre-defined criteria were
      traced. RESULTS: A total of 481 (public) and 553 (private) records were included.
      Median duration of follow-up was about 14 months. Cumulative retention and LTF
      proportions were 66.5 and 32.8% (public), and 82.6 and 11.0% (private)
      respectively. LTF rates at third, sixth, ninth  and twelfth months were 7.5,
      19.3, 25.4 and 29.6% respectively (public), and 4.1, 7.1, 9.0 and 10.0%
      (private). LTF was higher among males, patients with CD4(+) cell count <=200 and
      public programme enrollees. For the public  facility, 56.7% of 104 traceable
      patients were dead and 38.8% were alive; the figures were 34.2 and 60.5% of 46
      patients respectively for the private. Most deaths had occurred by the third
      month. CONCLUSION: Not all patients enrolled for treatment were  retained. Though
      some died, many were LTF, lived within the community, and could develop and
      transmit resistant viral stains. Most traced patients were dead by the third
      month and poor contact information limited the effectiveness of tracing.
      Antiretroviral treatment programmes need to improve  documentation processes and
      develop and implement tracing strategies.

PMID- 22595275
TI  - Effectiveness of antenatal screening for sickle cell trait: the impact on women's
      self-report of sickle cell trait status.
AB  - OBJECTIVES: The sickle gene frequency in the Jamaican population has not changed
      over a generation. It is unknown whether routine antenatal screening for sickle
      cell trait (SCT) has affected women's knowledge of their SCT status. The aim of
      this study  was to compare the prevalence of self-reported SCT in parous women to
      the prevalence in nulliparous women, men and to the observed prevalence of SCT
      measured in an antenatal clinic. METHODS: All participants in the nationally
      representative Jamaica Health and Lifestyle Survey 2008  were asked whether they
      had the SCT. The impact of gender, age, educational attainment, geographical
      location, and pregnancy on self-reported SCT were assessed. The prevalence of SCT
      in women attending a large antenatal clinic concurrently was compared to that
      reported by women of child-bearing  age in the lifestyle survey. RESULTS: Self
      report significantly underestimated the prevalence of SCT (2.9% versus 10.1%,
      P<0.001). Those with secondary education were more likely than those with
      presecondary education (P = 0.01)  and women more likely than men (3.2% versus
      1.1%, P = 0.001) to report having SCT. Women who had been pregnant were no more
      likely than other women to report having SCT (3.1% versus 4.1%, P = 0.4).
      CONCLUSIONS: Attendance at antenatal clinic where SCT screening is routine, is
      not associated with increased self-report of SCT. Screening programs must ensure
      that, as well as technically accurate screening, there is effective communication
      of the results of screening for SCT to those tested to help reduce  the public
      health burden of sickle cell disease in tropical countries.

PMID- 22595273
TI  - Molecular detection and analysis of spotted fever group Rickettsia in patients
      with fever and rash at a tertiary care centre in Tamil Nadu, India.
AB  - BACKGROUND: Detection of specific targets by PCR is used to confirm a diagnosis
      of spotted fever, but serological tests are still widely used. In this
      prospective study, nested PCR was performed on skin biopsy specimens to confirm
      the diagnosis of spotted fever. METHODS: In 58 clinically suspected cases of
      spotted fever, nested PCR, to detect gltA, 17 kDa lipoprotein antigen gene (17
      kDa), ompA and ompB, from skin biopsy of the rash was performed. Sequencing was
      carried on amplicons representing the four targets to confirm specificity  of
      amplification. This was followed by phylogenetic analysis using MEGA version 4.0
      software. RESULTS: The gltA, 17 kDa, ompA, and ompB genes were detected from skin
      biopsy specimens in 38, 23, 27, and 22 individuals. Sequence analysis revealed
      that the  gltA, 17 kDa, ompA, and ompB sequences belonged to spotted fever group
      (SFG) rickettsia. Of the six partial ompA gene sequences, only one was dissimilar
      to the previously reported 'Candidatus Rickettsia kellyi'. CONCLUSION: Further 
      evidence indicates that SFG rickettsiae resembling 'Candidatus Rickettsia kellyi'
      cause fever and rash in southern India. More detailed phylogenetic analysis
      following isolation of rickettsia in culture is required for providing
      irrefutable proof for the occurrence of novel  spotted fever rickettsiae in this
      region.

PMID- 22595276
TI  - Prevalence of intestinal parasitic infections among primary schoolchildren in
      areas devoid of sanitation in northwestern Kingdom of Swaziland, Southern Africa.

PMID- 22595277
TI  - Big insights from a small outbreak.

PMID- 22595278
TI  - Identifying an essential interaction between malaria parasites and erythrocytes
      unlocks the door to promising vaccine targets.

PMID- 22595280
TI  - Expanding the chemical palate of cells by combining systems biology and metabolic
      engineering.
AB  - The field of Metabolic Engineering has recently undergone a transformation that
      has led to a rapid expansion of the chemical palate of cells. Now, it is
      conceivable to produce nearly any organic molecule of interest using a cellular
      host. Significant advances have been made in the production of biofuels,
      biopolymers and precursors, pharmaceuticals and nutraceuticals, and commodity and
      specialty chemicals. Much of this rapid expansion in the field has been, in part,
      due to synergies and advances in the area of systems biology. Specifically, the
      availability of functional genomics, metabolomics and transcriptomics data has
      resulted in the potential to produce a wealth of new products, both natural and
      non-natural, in cellular factories. The sheer amount and diversity of this data
      however, means that uncovering and unlocking novel chemistries and insights is a
      non-obvious exercise. To address this issue, a number of computational tools and
      experimental approaches have been developed to help expedite the design process
      to create new cellular factories. This review will highlight many of the systems
      biology enabling technologies that have reduced the design cycle for engineered
      hosts, highlight major advances in the expanded diversity of products that can be
      synthesized, and conclude with future prospects in the field of metabolic
      engineering.

PMID- 22595281
TI  - Association of HLA-alleles with the immune regulation of chronic viral
      infections.
AB  - Cytotoxic CD8 T lymphocytes (CTLs) have an astonishing ability to eliminate
      pathogen-infected cells. However, if uncontrolled, these CTLs could cause
      devastating pathology to host tissues. CD8(+) effector T cells, therefore,
      interact with antigen-presenting cells and other immune cells, such as regulatory
      T cells (Tregs), to regulate further on-site expansion and differentiation of the
      effector cells. This ensures protection of the host with minimal bystander
      pathological consequences. During prolonged chronic infections CTLs, however,
      often lose effector function. Induction of multiple inhibitory pathways is
      emerging as a major regulator converting effector CTLs into exhausted CTLs during
      chronic viral infections such as HIV, HCV and HBV. The mechanisms involved in
      induction of exhaustion during chronic viral infections are the focus of this
      article. Blockade of inhibitory pathways could potentially restore functional
      capabilities to exhausted CTLs and represents a potential immune-based
      intervention in chronic viral infections.

PMID- 22595282
TI  - Human fetal tau protein isoform: possibilities for Alzheimer's disease treatment.
AB  - While early 1990s reports showed the phosphorylation pattern of fetal tau protein
      to be similar to that of tau in paired helical filaments (PHF) in Alzheimer's
      disease (AD), neither the molecular mechanisms of the transient developmental
      hyperphosphorylation of tau nor reactivation of the fetal plasticity due to re
      expression of fetal protein kinases in the aging and AD human brain have been
      sufficiently investigated. Here, we summarize the current knowledge on fetal tau,
      adding new data on the specific patterns of tau protein and mRNA expression in
      the developing human brain as well as on change in tau phosphorylation in the
      perforant pathway after entorhinal cortex lesion in mice. As fetal tau isoform
      does not form PHF even in a highly phosphorylated state, understanding its
      expression and post-translational modifications represents an important avenue
      for future research towards the development of AD treatment and prevention.

PMID- 22595283
TI  - Mitochondrial chaperone DnaJA3 induces Drp1-dependent mitochondrial
      fragmentation.
AB  - Mitochondrial morphology is dynamic and controlled by coordinated fusion and
      fission pathways. The role of mitochondrial chaperones in mitochondrial
      morphological changes and pathology is currently unclear. Here we report that
      altered levels of DnaJA3 (Tid1/mtHsp40) a mitochondrial member of the DnaJ
      protein family, and heat shock protein (Hsp) co-chaperone of matrix 70 kDa Hsp70
      (mtHsp70/mortalin/HSPA9), induces mitochondrial fragmentation. Suppression of
      DnaJA3 induced mitochondrial fragmentation in HeLa cells. Elevated levels of
      DnaJA3 in normal Hs68 fibroblast cells and HeLa, SKN-SH, U87 and U251 cancer cell
      lines induces mitochondrial fragmentation. Mitochondrial fragmentation induction
      was not observed in HeLa cells when other DnaJA family members, or mitochondrial
      DnaJ protein HSC20, were ectopically expressed, indicating that the effects on
      mitochondrial morphology were specific to DnaJA3. We show that the DnaJ domain
      (amino acids 88-168) of DnaJA3 is sufficient for the induction of mitochondrial
      fragmentation. Furthermore, an H121Q point mutation of the DnaJ domain, which
      abrogates interaction and activation of mtHsp70 ATPase, eliminates fragmentation
      induced by DnaJA3. This suggests that DnaJA3 interaction with mtHsp70 may be
      critical in mitochondrial morphological changes. DnaJA3-induced mitochondrial
      fragmentation was dependent on fission factor dynamin-related protein 1 (Drp1).
      Ectopic expression of the mitofusins (Mfn1 and Mfn2), however, does not rescue
      DnaJA3-induced mitochondrial fragmentation. Lastly, elevated levels of DnaJA3
      inducing mitochondrial fragmentation were associated with reduction in cell
      viability. Taken together, elevated DnaJA3 induces Drp1-depedendent mitochondrial
      fragmentation and decreased cell viability.

PMID- 22595284
TI  - Detecting temporal expressions in medical narratives.
AB  - BACKGROUND: Clinical practice and epidemiological information aggregation require
      knowing when, how long, and in what sequence medically relevant events occur. The
      Temporal Awareness and Reasoning Systems for Question Interpretation (TARSQI)
      Toolkit (TTK) is a complete, open source software package for the temporal
      ordering of events within narrative text documents. TTK was developed on
      newspaper articles. We extended TTK to support medical notes using veterans'
      affairs (VA) clinical notes and compared it to TTK. METHODS: We used a
      development set consisting of 200 VA clinical notes to modify and append rules to
      TTK's time tagger, creating Med-TTK. We then evaluated the performances of TTK
      and Med-TTK on an independent random selection of 100 clinical notes. Evaluation
      tasks were to identify and classify time-referring expressions as one of four
      temporal classes (DATE, TIME, DURATION, and SET). The reference standard for this
      test set was generated by dual human manual review with disagreements resolved by
      a third reviewer. Outcome measures included recall and precision for each class,
      and inter-rater agreement scores. RESULTS: There were 3146 temporal expressions
      in the reference standard. TTK identified 1595 temporal expressions. Recall was
      0.15 (95% confidence interval [CI] 0.12-0.15) and precision was 0.27 (95% CI 0.25
      0.29) for TTK. Med-TTK identified 3174 expressions. Recall was 0.86 (95% CI 0.84
      0.87) and precision was 0.85 (95% CI 0.84-0.86) for Med-TTK. CONCLUSION: The
      algorithms for identifying and classifying temporal expressions in medical
      narratives developed within Med-TTK significantly improved performance compared
      to TTK. Natural language processing applications such as Med-TTK provide a
      foundation for meaningful longitudinal mapping of patient history events among
      electronic health records. The tool can be accessed at the following site:
      http://code.google.com/p/med-ttk/.

PMID- 22595285
TI  - Tumor necrosis factor-alpha (TNF-alpha)-mediated in vitro human retinal pigment
      epithelial (RPE) cell migration mainly requires Akt/mTOR complex 1 (mTORC1), but
      not mTOR complex 2 (mTORC2) signaling.
AB  - When rhegmatogenous retinal detachment occurs, tumor necrosis factor-alpha (TNF
      alpha) among other cytokines leaks into the subretinal space, induces resident
      retinal pigment epithelial (RPE) cells to migrate, which is the initial step of
      proliferative vitreoretinopathy (PVR). In the current study, we aim to understand
      how this is regulated by focusing the cellular mechanisms involved. Here we
      identified an Akt/Tuberous sclerosis protein 2 (TSC2)/mTOR complex1 (mTORC1)
      signaling pathway after TNF-alpha treatment to mediate RPE cell migration.
      Suppression of mTORC1 activation, either by its inhibitor rapamycin, or by
      activation of its suppressor AMP activated protein kinase (AMPK), inhibited TNF
      alpha-mediated RPE cell migration, while RNA interference (RNAi)-mediated
      knocking-down of SIN1 or Rictor, two key components of mTOR complex 2 (mTORC2),
      had no significant effect on TNF-alpha-induced RPE cell migration. Our data
      provide initial evidence that TNF-alpha-mediated in vitro RPE cell migration
      mainly requires Akt/mTORC1, but not mTORC2 signaling. The results of this study
      may lead to indentify novel signaling targets against PVR.

PMID- 22595286
TI  - Contingent choice. Exploring the relationship between sweetened beverages and
      vegetable consumption.
AB  - Adults and children are repeatedly exposed to the pairing of food and drink as
      found in meal deals and "combos". There may arise from this indoctrination, a
      contingent relationship between drink context and food preference. Our multi
      method research examines food and drink combining. A survey-based study examines
      the food and drink pairing preferences of adults (N=60), while a laboratory study
      with young children (N=75, aged three to five) examines the role of drink context
      on vegetable consumption. The adult survey finds strong food and drink combining
      preferences. The pairing of soft drinks with calorie dense foods is regarded
      favorably, while the pairing of soft drinks with vegetables is not. In child food
      trials, vegetable consumption is not influenced by the child's fussiness but is
      influenced by the drink accompaniment. In limited contexts, these findings
      demonstrate the contingent relationship between drink context and food
      consumption. Both palate preference and associative learning may be mechanisms
      driving the effects of drink context on food consumption. The findings suggest
      simple consumer strategies that might be employed to change dietary patterns
      (e.g., drink water with meals), and hold straightforward policy implications
      (e.g., increase water as the default option in meal deals).

PMID- 22595287
TI  - Regulatory focus, self-efficacy and outcome expectations as drivers of motivation
      to consume healthy food products.
AB  - In this paper we apply the principle of Regulatory Focus Theory to investigate
      the interaction between self-efficacy and outcome expectations on individuals'
      intentions to adopt health behaviors. The participants, 959 individuals (Survey
      1) and 2400 individuals (Survey 2), reported self-efficacy beliefs and outcome
      expectations with regard to the consumption of omega-3 supplements and omega-3
      enriched food products. We found that the relationship prevention outcome
      expectations-intention was significantly attenuated at low levels of self
      efficacy and strengthened at high levels of self-efficacy, respectively; whereas,
      the relationship promotion outcome expectations-intention was unaffected by the
      perceived levels of self-efficacy. The implications suggest that consumers'
      motivation to adopt healthy food products, such as omega-3 supplements and omega
      3 enriched products, should be encouraged by stimulating promotion outcome
      expectations. However, when a prevention frame is used, the individuals'
      motivation should be significantly enhanced by self-efficacy beliefs.

PMID- 22595288
TI  - Reinforcement of anticipatory eating by short as well as long fasts.
AB  - Rats can learn to anticipate the omission of subsequent meals by increasing food
      intake. Our previous reports have analysed group means at each trial but that
      does not allow for rats learning at different speeds. This paper presents instead
      a rat-by-rat analysis of all the raw data from previous experiments. The re
      analysis supports the published evidence that the capacity for reinforcement
      generated by withholding of food is greater after a longer fast than after a
      shorter fast, but that the learning is quicker after the shorter fast. The
      individualised analyses also extend the evidence that the pattern of learning,
      extinction and re-learning with shorter fasts is similar to that with longer
      fasts. These findings indicate that, contrary to our previous interpretation, a
      single learning mechanism can explain the effects of both durations of food
      deprivation.

PMID- 22595289
TI  - Associations of food preferences and household food availability with dietary
      intake and quality in youth with type 1 diabetes.
AB  - The objective of this study was to examine associations of food preferences and
      availability with dietary intake in youth with type 1 diabetes, for whom dietary
      intake and quality are essential to disease management. Youth (n=252, age 13.2+/
      2.8 y, diabetes duration 6.3+/-3.4 y) reported preferences and parents reported
      household availability for 61 food items categorized as fruit, vegetables, whole
      grains, refined grains and fats/sweets. Youth energy-adjusted daily servings of
      food groups, Healthy Eating Index-2005 and Nutrient Rich Foods 9.3 scores were
      calculated from 3-day diet records. Associations of dietary intake and quality
      variables with preference and availability of all food groups were evaluated by
      linear regressions adjusted for sociodemographic characteristics. Fruit and whole
      grain intake were positively related to corresponding preference and
      availability; whole grain intake and refined grain availability were inversely
      related. Vegetable, refined grain and fats/sweets intake were unrelated to
      preference and availability. Diet quality measures were related positively to
      fruit preference and whole grain availability and inversely to refined grains
      availability. Findings indicate associations of dietary intake with food
      preference and availability vary by food group in youth with type 1 diabetes.
      Measures of overall dietary quality were more consistently associated with food
      group availability than preferences.

PMID- 22595290
TI  - Snail, a transcriptional regulator, represses adiponectin expression by directly
      binding to an E-box motif in the promoter.
AB  - OBJECTIVE: Adiponectin is a hormone that modulates many metabolic processes and
      is exclusively expressed in adipose tissue. However, complete understanding of
      the factors that regulate adiponectin expression is lacking. The following were
      investigated: (1) functional analysis of the human adiponectin promoter, (2)
      putative adiponectin repressor sequence activity in 3T3-L1 adipocytes using
      promoter mutagenesis, (3) whether Snail, an E-box binding transcription factor,
      binds this repressor sequence, (4) if Snail regulates adiponectin expression in
      3T3-L1 pre-adipocytes. MATERIALS/METHODS: To further understand how adiponectin
      expression is regulated, we isolated the human adiponectin promoter and analyzed
      its activity after serial deletions. RESULTS: We found a negative cis-regulatory
      element located in the adiponectin proximal promoter sequence (-174 to -152 bp),
      which contained an E-box site (CAACTG). The DNA binding activity of this putative
      negative regulatory factor was found to be sequence-specific and the binding
      activity is decreased during adipocyte differentiation time-dependently. Affinity
      chromatography identified the zinc-finger transcription factor Snail (SNAI1) as
      the putative negative regulatory factor. Chromatin immunoprecipitation assay and
      electrophoretic mobility shift assay confirmed that Snail binds to this negative
      cis-regulatory element in pre-adipocytes, exclusively. Inhibition of Snail
      expression using small interfering RNA techniques increased adiponectin
      expression in 3T3-L1 adipocytes, while overexpression of Snail reduced
      adiponectin expression. Furthermore, we observed an inverse relation between the
      expression of Snail and the expression of CCAAT-enhancer-binding protein alpha
      and peroxisome proliferator-activated receptor gamma, which are transcription
      factors that regulate adipogenesis. CONCLUSIONS: Snail is a novel regulator of
      adiponectin expression and probably has a role in regulating adipogenesis.

PMID- 22595291
TI  - Unexpected multiplet patterns induced by the Haupt-effect.
AB  - An NMR polarization up to a factor of 100 compared to the room temperature signal
      of a fully equilibrated sample and up/down multiplets are observed when 4-methyl
      pyridine or toluene are taken rapidly from liquid helium temperatures to room
      temperature by dissolving in acetone-d6. These findings result from the inherent
      coupling between rotational and nuclear spin states in methyl groups which can
      act as quantum rotors. The temperature jump causes changes in rotational and spin
      energy level population due to symmetry rules that is known as the Haupt-effect.

PMID- 22595292
TI  - Combining dipolar-quadrupolar correlation spectroscopy with isotropic shift
      resolution in magic-angle-spinning 17O NMR.
AB  - We explore the effect of heteronuclear dipolar recoupling on the satellite and
      multiple-quantum transitions of a half-integer-spin quadrupolar nucleus coupled
      to a single spin-12. A three-dimensional experiment is introduced that resolves
      different quadrupolar sites whilst allowing simultaneous extraction of the
      quadrupolar coupling constants, asymmetry parameters of the electric field
      gradient, and the isotropic shifts of the quadrupolar nucleus. The experiment
      also enables estimation of the heteronuclear dipolar coupling constant between
      the spin-1/2 and half-integer spin quadrupolar nucleus. The relative orientation
      of the dipolar tensor with respect to the quadrupolar tensor can be estimated by
      comparing experiments and simulations. Experimental results are shown on a sample
      of brucite, Mg((17)OH)(2), where the (1)H-(17)O bond distance is estimated.

PMID- 22595293
TI  - Earth field NMR with chemical shift spectral resolution: theory and proof of
      concept.
AB  - A new method for obtaining an NMR signal in the Earth's magnetic field (EF) is
      presented. The method makes use of a simple pulse sequence with only DC fields
      which is much less demanding than previous approaches in terms of the pulses'
      rise and fall times. Furthermore, it offers the possibility of obtaining NMR data
      with enough spectral resolution to allow retrieving high resolution molecular
      chemical shift (CS) information - a capability that was not considered possible
      in EF NMR until now. Details of the pulse sequence, the experimental system, and
      our specially tailored EF NMR probe are provided. The experimental results
      demonstrate the capability to differentiate between three types of samples made
      of common fluorine compounds, based on their CS data.

PMID- 22595294
TI  - Repetitive sideband-selective double frequency sweeps for sensitivity enhancement
      of MAS NMR of half-integer quadrupolar nuclei.
AB  - A sensitivity enhancement scheme aiming at selective adiabatic inversion of a
      single set of satellite transition sidebands under magic angle spinning has been
      employed on samples of albite containing a single moderately distorted (27)Al
      site and zoisite containing two highly distorted octahedral (27)Al sites. Overall
      enhancements of ~2.5 for albite and ~3 for the two AlO(6) sites of zoisite are
      reported by applying this scheme at different spinning speeds reflecting the
      versatility of this enhancement scheme which achieves significant signal-to-noise
      enhancements for the systems with moderately high quadrupolar coupling and high
      quadrupolar coupling. Repeating the sensitivity enhancement scheme and signal
      readout several times without allowing for spin-lattice relaxation leads to
      sensitivity enhancements of factors of ~4 for albite and ~5 for zoisite which
      substantially increases the detectability of the quadrupolar sites. The
      effectiveness of this scheme at high magnetic field under very fast magic angle
      spinning has been demonstrated. Finally, the possibility of performing spectral
      editing by selective enhancement of one of the quadrupolar sites in zoisite
      whilst keeping the other site unaffected has been explored.

PMID- 22595295
TI  - Level anti-crossings in ParaHydrogen Induced Polarization experiments with Cs
      symmetric molecules.
AB  - Hyperpolarization by means of ParaHydrogen Induced Polarization (PHIP) has found
      increasing applications since its discovery. However, in the last decade only a
      few experiments have been reported describing the hydrogenation of symmetric
      molecules. A general AA'BB' system is studied here. Calculations of the spin
      dynamics with the density matrix formalism support the experimental findings,
      providing profound understanding of the experiments in Cs-symmetric molecules.
      Level anti-crossings between states related to the triplet and the singlet state
      of one pair of the protons are identified as being responsible for
      hyperpolarization transfer in a PHIP experiment, when the former p-H(2) protons
      occupy the sites AA'. The hydrogenation of acetylene dicarboxylic acid
      dimethylester with parahydrogen is used to illustrate the case. The theoretical
      treatment applied to this particular reaction explains the signal enhancements in
      both groups of protons in the spectrum when the sample is placed in the proper
      magnetic field strength, including the phase inversion of the signal of the
      methyl group. The treatment described here can be extended to every molecule
      which can be approximated as an AA'BB' system.

PMID- 22595296
TI  - Animal models of heart failure: a scientific statement from the American Heart
      Association.

PMID- 22595297
TI  - Optic disc torsion direction predicts the location of glaucomatous damage in
      normal-tension glaucoma patients with myopia.
AB  - OBJECTIVE: To characterize optic disc tilt and torsion in normal-tension glaucoma
      (NTG) patients with myopia and to evaluate the relationship between optic disc
      tilt and torsion with the location of visual field (VF) defect. DESIGN:
      Retrospective, case-control design. PARTICIPANTS: Two hundred twenty-five NTG
      patients. METHODS: Patients were divided into a myopic NTG group (spherical
      equivalent more than -2.00 diopters [D] or axial length more than 24.0 mm; n =
      166) and nonmyopic NTG group (spherical equivalent less than -0.50 D or axial
      length less than 24.0 mm; n = 59). Disc tilt, which was identified by the tilt
      ratio, disc torsion, and area of peripapillary atrophy (PPA), was measured from
      disc photographs. Patients were divided further into superior and inferior defect
      groups according to the location of the VF defect in the pattern deviation map.
      Logistic regression analysis was used to determine the relationship between
      ocular factors, including tilt ratio, torsion degree, and the VF defect location.
      MAIN OUTCOME MEASURES: Tilt ratio, torsion degree, PPA area, and location of VF
      defect. RESULTS: Among 225 NTG eyes, 166 (73.8%) were myopic eyes. The myopic NTG
      group was significantly younger (42.85 years) than the nonmyopic NTG group (60.73
      years). Disc tilt (45.8%) and torsion (75.9%) were significantly more prevalent
      in the myopic NTG group than in the nonmyopic NTG group. Although just short of
      statistical significance (P = 0.057), PPA area was larger in the myopic NTG
      group. The VF defect location was significantly different between the 2 groups,
      with superior defects more prevalent in the myopic NTG group (69.9%; P<0.001).
      Torsion degree was significantly different in the superior defect group (18.45
      degrees ) compared with the inferior defect group (-3.81 degrees ; P = 0.001).
      Torsion degree was the only factor related to VF defect location in both
      univariate (P = 0.001) and multivariate (P = 0.014) logistic regression analyses.
      CONCLUSIONS: Korean NTG patients had a high prevalence of myopia and young age.
      Optic disc tilt and torsion were highly prevalent in Korean NTG patients with
      myopia. The direction of the optic disc torsion may predict the location of
      damage.

PMID- 22595298
TI  - Effects of the presence of the body in helmet oblique impacts.
AB  - The oblique impact methods of motorcycle helmet standards prescribe using an
      isolated headform. However, in accidents the presence of the body may influence
      impact responses of the head and helmet. In this study, the effects of the
      presence of the body, in helmet oblique impacts, are investigated. Using the
      Finite Element method, oblique impacts of a commercially available helmet,
      coupled with a model of the human body, are simulated. A comparison between full
      body impacts and those performed with an isolated headform show that the presence
      of the body modifies the peak head rotational acceleration by up to 40%. In
      addition, it has a significant effect on head linear acceleration and the
      crushing distance of the helmet's liner. To include the effect of the body on
      head rotational acceleration in headform impacts, modifying inertial properties
      of the headform is proposed. The modified inertial properties are determined for
      a severe and frequent impact configuration. The results of helmet impacts
      obtained by using the modified headform are in very good agreement with those of
      full-body impacts; this verifies the accuracy of the proposed method.

PMID- 22595299
TI  - Driver perception of roadside configurations on two-lane rural roads: Effects on
      speed and lateral placement.
AB  - This paper reports the results of a driving simulator study which sought to
      analyze the effect that: (a) three roadside configurations on a two-lane rural
      road lined with trees have on speed and lateral position of the driver, depending
      on different cross-sections as well as geometric elements; (b) the beginning of
      the guardrail barrier has upon the driver's behavior whenever this occurs on the
      left curve, right curve or tangent. A two-lane rural road lined with trees was
      designed and implemented in an advanced-interactive driving simulator. Two
      different cross-sections (with and without a shoulder), which were combined with
      three roadside configurations (only trees, trees and barriers, trees and barriers
      having undergone a treatment), were tested. Six road scenarios were then
      analyzed. Thirty-six drivers (33 were deemed to be valid and used for the
      analysis) drove in the simulator using these scenarios and the speed and lateral
      placement values were collected. Statistical analysis showed that the driver
      behavior was only affected by the cross-sections and geometric elements but not
      by roadside configurations. Although the presence of trees along the road
      represents a factor that increases the severity of run-off-road accidents,
      drivers do not change their behavior when barriers are not present. Concerning
      the effects of the beginning of the barrier, MANOVA revealed a main effect for
      roadside configuration on lateral position but not on speed. There was also a
      clear tendency of drivers to "cut" both the right curves as well as the left
      curves in order to minimize the speed reduction in the tangent-curve-tangent
      transition. These main results allow useful suggestions to be made as regards
      safety measures for improving road safety on two-lane rural roads lined with
      trees.

PMID- 22595300
TI  - Interactions among capsid proteins orchestrate rotavirus particle functions.
AB  - Rotaviruses are members of the Reoviridae family of non-enveloped viruses and
      important etiologic agents of acute gastroenteritis in infants and young
      children. In recent years, high-resolution structures of triple-layered rotavirus
      virions and the constituent proteins have provided valuable insights into
      functions. Of note, structural studies have revealed the position of the viral
      RNA-dependent RNA polymerase, VP1, within the inner capsid, which in turn
      provides clues about the location of the viral capping machinery and the route of
      viral transcript egress. Mechanisms by which the viral spike protein, VP4,
      mediates receptor binding and membrane penetration have also been aided by high
      resolution structural studies. Future work may serve to fill the remaining gaps
      in understanding of rotavirus particle structure and function.

PMID- 22595301
TI  - Renal denervation in moderate to severe CKD.
AB  - Sympathetic activation contributes to the progression of CKD and is associated
      with adverse cardiovascular outcomes. Ablation of renal sympathetic nerves
      reduces sympathetic nerve activity and BP in patients with resistant hypertension
      and preserved renal function, but whether this approach is safe and effective in
      patients with an estimated GFR (eGFR) < 45 ml/min per 1.73 m(2) is unknown. We
      performed bilateral renal denervation in 15 patients with resistant hypertension
      and stage 3-4 CKD (mean eGFR, 31 ml/min per 1.73 m(2)). We used CO(2) angiography
      in six patients to minimize exposure to contrast agents. Estimated GFR remained
      unchanged after the procedure, irrespective of the use of CO(2) angiography. Mean
      baseline BP +/- SD was 174 +/- 22/91 +/- 16 mmHg despite the use of 5.6 +/- 1.3
      antihypertensive drugs. Mean changes in office systolic and diastolic BP at 1, 3,
      6, and 12 months were -34/-14, -25/-11, -32/-15, and -33/-19 mmHg, respectively.
      Night-time ambulatory BP significantly decreased (P<0.05), restoring a more
      physiologic dipping pattern. In conclusion, this study suggests a favorable short
      term safety profile and beneficial BP effects of catheter-based renal nerve
      ablation in patients with stage 3-4 CKD and resistant hypertension.

PMID- 22595302
TI  - Off-pump versus on-pump coronary artery bypass grafting outcomes stratified by
      preoperative renal function.
AB  - Clinical trials of off-pump coronary artery bypass grafting (CABG) have largely
      excluded patients with CKD. Here, we sought to determine whether pump status
      affects outcomes in patients with CKD. Using a nonrandomized cohort of 742,909
      non-emergent, isolated CABG cases, which included 158,561 off-pump cases, in the
      Society of Thoracic Surgery Database from 2004 through 2009, we evaluated the
      association between pump status (off-pump versus on-pump) and in-hospital death
      or incident renal replacement therapy (RRT) across strata of preoperative renal
      function. We used propensity methods to adjust patient- and center-level analyses
      for imbalances in baseline patient risk. Patients who received on-pump and off
      pump CABG had similar mean age and distribution of preoperative estimated GFR
      (eGFR). In a propensity-weighted analysis, off-pump CABG was associated with a
      reduction in the composite in-hospital death or RRT, with patients having lower
      preoperative renal function exhibiting greater benefit, on average. The risk
      difference (on-pump minus off-pump) ranged from 0.05 (95% confidence interval, 
      0.06 to 0.16) per 100 patients for eGFR >= 90 ml/min per 1.73 m(2) to 3.66 (95%
      confidence interval, 2.14-5.18) per 100 patients for eGFR 15-29 ml/min per 1.73
      m(2). Both component endpoints suggested the same trend. In summary, these data
      suggest that patients with CKD experience less death or incident RRT when treated
      with off-pump compared with on-pump CABG. The reduction in incident RRT, not
      death, drove this effect on the composite among patients with low eGFR.
      Prospective trials comparing these procedures in patients with impaired
      preoperative renal function are warranted.

PMID- 22595303
TI  - On-line hemodiafiltration: not a self-fulfilling prophecy.

PMID- 22595304
TI  - Plant growth stimulation in Prunus species plantlets by BTH or OTC treatments
      under in vitro conditions.
AB  - The effects of benzothiadiazole (BTH) and L-2-oxothiazolidine-4-carboxylic acid
      (OTC) on the growth and viral content of micropropagated, Plum pox virus (PPV)
      infected peach [(Prunus persica (L.) Batsch] 'GF305' plantlets were analyzed. Low
      BTH and OTC concentrations resulted in a significant increase in the growth of
      GF305 peach and plum plants, with greater effects in PPV-infected than in healthy
      GF305 peach plantlets. Neither BTH nor OTC reduced the virus content. In fact,
      the highest growth and viral contents coincided, especially with the 10 MUM BTH
      treatment. Differing effects on the antioxidative metabolism of PPV-infected
      GF305 peach plantlets were observed, depending on the compound and the
      concentration used: BTH decreased GSH, whereas OTC increased it. In PPV-infected
      plants, the 50 MUM OTC treatment produced a decrease in ascorbate peroxidase,
      catalase, and glutathione peroxidase, but an increase in superoxide dismutase.
      However, BTH produced a rise in peroxidase activity. Both 10 MUM BTH and 50 MUM
      OTC produced H2O2 accumulation that was correlated with the histochemical
      detection of H2O2 by 3,3'-diaminobenzidine staining. PPV infection induced NPR1
      expression and a synergistic effect occurred in the presence of 50 MUM OTC, since
      this compound produced an up-regulation of NPR1 in both healthy and PPV-infected
      GF305 peach plantlets. The results showed that GSH, as previously suggested,
      and/or H2O2 could be involved in the regulation of NPR1 expression. Globally, the
      results show that both OTC and BTH improved the vigor of Prunus species,
      including peach and plum, under in vitro conditions, producing positive effects
      on growth, antioxidative metabolism and NPR1 expression. All of these
      improvements could be critical for more successful ex vitro acclimatization as
      well as for improved responses to different stresses.

PMID- 22595305
TI  - Autophagy can repair endoplasmic reticulum stress damage of the passive Heymann
      nephritis model as revealed by proteomics analysis.
AB  - Membranous nephropathy is a common cause of nephrotic syndrome in adults.
      Although many mechanisms have been proposed, whole proteomic research is still
      lacking. We analyzed the passive Heymann nephritis animal model using label-free
      quantitative proteome technology. Results showed 160 differential proteins
      between control and PHN model groups at days 14 and 21. The expression level of
      endoplasmic reticulum stress (ERS)-associated protein GRP78 and GRP94 protein was
      up-regulated on day 14 or 21, which was confirmed by Western blotting. The
      results also showed that the autophagy marker LC3 was up-regulated in the models.
      Furthermore, we used tunicamycin to induce ERS of podocytes in vitro to
      investigate the mechanism. Results of Western blotting revealed that the
      expression of GRP78, GRP94, and LC3 was up-regulated, while that of the
      cytoskeletal protein tubulin-beta was down-regulated, and immunofluorescence
      displayed disordered distribution of tubulin-beta. These suggest that ERS plays
      an important role in podocyte damage. Autophagy can repair the cytoskeleton
      damage caused by ERS as a protective mechanism. This provides an important basis
      for a thorough understanding of the mechanism of podocyte damage and the
      pathogenesis of membranous nephropathy.

PMID- 22595307
TI  - The detection of HBsAg mutants expressed in vitro using two different
      quantitative HBsAg assays.
AB  - BACKGROUND: The quantification of hepatitis-B surface antigen (HBsAg) is useful
      to identify inactive carriers in chronically HBV infected patients and to predict
      interferon treatment outcome. OBJECTIVE: To compare two quantitative HBsAg assays
      for the detection of HBsAg mutants expressed in vitro. STUDY DESIGN: HBsAg
      mutants (n=35) were expressed in HuH7 cells and the supernatants were tested in
      two different quantitative HBsAg assays (Architect, Abbott and Elecsys, Roche).
      RESULTS: All HBsAg mutants were detected by both assays, but in general the
      results of the Architect system were higher than those of the Elecsys system. The
      detection of HBsAg mutants in comparison to wild type was similar using both
      assays. However, HBsAg mutation T123A was under quantified by the Architect,
      whereas HBsAg mutations P142L, P142S and G145K yielded lower results in the
      Elecsys system. CONCLUSIONS: Even though HBsAg assays are optimised for the
      detection of HBsAg mutants, discrepant results were obtained for some HBsAg
      mutants in two quantitative HBsAg assays. These findings have to be considered
      when testing samples from one patient with two different quantitative HBsAg
      assays.

PMID- 22595306
TI  - Complex patterns of HCV epidemic in Suzhou: evidence for dual infection and HCV
      recombination in East China.
AB  - BACKGROUND: HCV transmission is closely associated with injection drug use (IDU),
      and co-circulation of multiple subtypes has been found among injection drug users
      (IDUs) in China. OBJECTIVES: To investigate HCV subtype characterizations among
      IDUs and general population (GP) in Suzhou, a city at the important "Hu-ning"
      transportation line. STUDY DESIGN: During January 2010 to May 2011, 123 HCV
      positive plasma from IDUs and 131 stored HCV positive sera from general
      individuals were collected in Suzhou. HCV C/E2 and NS5B fragments were amplified
      using a new multiple RT-nested PCR strategy and subsequent sequenced. Genotypes
      were characterized by phylogenetic analyses. RESULTS: Eight HCV subtypes (1a, 1b,
      2a, 3a, 3b, 6a, 6n, and 6u) were detected among Suzhou IDUs, and six subtypes
      (1b, 2a, 3a, 3b, 6a and 6n) among GP. HCV subtype distribution is distinct
      between IDUs and GP. Interestingly, we detected discrepancy of genotyping results
      between C/E2 and NS5B regions in one general individual, indicating the presence
      of HCV intersubtype recombinant in China. The recombinant belongs to a 3a/1b
      recombinant. We also detected dual infections in one general individual and two
      IDUs. They include dual infections between 1b and 3a, 3a and 6a, and two distinct
      lineages of 3b. CONCLUSIONS: Complex patterns of HCV epidemic among IDUs, as well
      as GP, in Suzhou, might imply a spread of HCV from IDUs to GP. The finding of one
      HCV 3a/1b intersubtype recombinant might represent the first report of HCV
      recombination in China.

PMID- 22595308
TI  - Human cytomegalovirus preferentially infects the neoplastic epithelium of
      colorectal cancer: a quantitative and histological analysis.
AB  - BACKGROUND: It has long been suggested that human cytomegalovirus (HCMV) might be
      involved in human oncogenesis. However, whether HCMV was associated with
      colorectal cancer (CRC) was still controversial. OBJECTIVE: To clarify whether
      HCMV specifically infects the tumorous tissue of CRC. STUDY DESIGN: Paired tumor
      and adjacent non-neoplastic CRC specimens were collected from 163 patients. HCMV
      DNA was detected and quantified through PCR and quantitative real-time PCR. Virus
      location was determined by in situ hybridization (ISH) of formalin-fixed paraffin
      embedded tissue sections with an HCMV-specific probe. RESULTS: By PCR, HCMV DNA
      was detected in 42.3% (69/163) of the tumor specimens, while only 5.6%(14/163)
      samples of adjacent non-neoplastic tissue were positive for HCMV (p<0.0001).
      Quantitative real-time PCR in 54 sample pairs revealed significantly higher viral
      copies in the tumor specimens than the adjacent non-neoplastic tissue specimens
      (p<0.001). By ISH, the nucleic acids of HCMV were detected in the cytoplasm of
      neoplastic epithelium. No hybridization was detected in the inflammatory
      infiltrates, submucosa, or other stromal tissues. CONCLUSIONS: HCMV
      preferentially infects the tumor epithelium of CRC. How the virus subsists in and
      interacts with the microenvironment of tumor epithelium of CRC should be studied.

PMID- 22595310
TI  - Visual cortex responses to suprachoroidal electrical stimulation of the retina:
      effects of electrode return configuration.
AB  - A clinically effective retinal prosthesis must evoke localized phosphenes in a
      retinotopic manner in response to stimulation of each of the retinal electrodes,
      evoke brightness cues over a wide dynamic range and function within safe stimulus
      limits. The effects of varying return configuration for retinal stimulation are
      currently unknown. To investigate this, we implanted a flexible, 7 * 12 electrode
      array into the suprachoroidal space of normally-sighted, anesthetized cats. Multi
      unit activity in the primary visual cortex was recorded in response to electrical
      stimulation using various return configurations: monopolar vitreous (MPV), common
      ground (CG), hexagonal (HX), monopolar remote (MPR) and bipolar (BP_N). MPV
      stimulation was found to be the most charge efficient and was most likely to
      induce cortical activity within safe charge limits. HX and CG stimulation were
      found to exhibit greater retinal selectivity compared to the MPV return at the
      expense of lower cortical yield and higher P50 charge levels, while cortical
      selectivity was unaffected by choice of return. Responses using MPR and widely
      spaced BP_N configurations were similar to those using the MPV return. These
      results suggest that choice of return configuration for a retinal prosthesis will
      be balanced between resolution and stimulation within safe charge limits.

PMID- 22595309
TI  - Respiratory viral pathogens associated with lower respiratory tract disease among
      young children in the highlands of Papua New Guinea.
AB  - BACKGROUND: Acute lower respiratory tract infections (ALRI) commonly result in
      fatal outcomes in the young children of Papua New Guinea (PNG). However,
      comprehensive studies of the viral aetiology of ALRI have not been conducted in
      PNG for almost 30 years. OBJECTIVES: To determine the viruses associated with
      ALRI among children living in the PNG highlands using sensitive molecular
      detection techniques. STUDY DESIGN: Pernasal swabs were collected routinely
      between 1 week and 18 months of age and also during episodes of ALRI, as part of
      a neonatal pneumococcal conjugate vaccine trial. A tandem multiplex real-time PCR
      assay was used to test for a comprehensive range of respiratory viruses in
      samples collected from 221 young children. Picornavirus typing was supported by
      DNA sequence analysis. RESULTS: Recognized pathogenic respiratory viruses were
      detected in 198/273 (73%) samples collected from children with no evidence of
      ALRI and 69/80 (86%) samples collected during ALRI episodes. Human rhinoviruses
      (HRV) species A, B and C were detected in 152 (56%) samples from non-ALRI
      children and 50 (63%) samples collected during ALRI episodes. Partial structural
      region sequences for two new species C rhinoviruses were added to the GenBank
      database. ALRI was associated with detection of adenovirus species B (p<0.01) or
      C (p<0.05), influenza A (p<0.0001) or respiratory syncytial virus (p<0.0001).
      Multiple viruses were detected more often during ALRI episodes (49%) than when
      children displayed no symptoms of ALRI (18%) (p<0.0001). CONCLUSIONS: The burden
      of infection with respiratory viruses remains significant in young children
      living in the PNG highlands.

PMID- 22595311
TI  - Effective mechanical properties of diaphyseal cortical bone in the canine femur.
AB  - The effective elastic modulus, yield strength, yield strain, ultimate strength,
      ultimate strain, strain energy density at yield and strain energy density at
      ultimate failure of femoral diaphyseal cortical bone were investigated on canine
      femurs. Four femurs representative of the canine population were selected from
      four statistically-determined clusters based on increasing size and weight
      comprising the Toy poodle (5 kg), Poodle (12 kg), German shorthaired pointer (25
      kg) and Doberman (50 kg). The zones of interest were the lateral, medial,
      cranial, and caudal quadrants of the mid-diaphysis. Effective mechanical
      properties were measured using quasi-static three-point bending tests on strips.
      The averages +/- SD were 15.6 +/- 2.6 GPa for effective elastic modulus, 174.3 +/
      32.1 MPa for yield strength, 0.012 +/- 0.003 for yield strain, 251.0 +/- 49.1
      MPa for ultimate strength, 0.021 +/- 0.005 for ultimate strain, 10.7 +/- 4.0J m(
      3) * 10(5) for strain energy density at Yield and 33.0 +/- 14.1 Jm(-3)* 10(5) for
      strain energy density at ultimate failure. Significant differences were found
      between dogs and the effective elastic modulus increased with breed weight and
      size (13.9 GPa for the Toy poodle to 17.2 GPa for the Doberman). The ultimate
      strength sigma(u) and strain energy density at ultimate failure U(u) were
      significantly lower in the Toy poodle than in the Poodle and German shorthaired
      pointer indicating that the cortical bone material in the Toy poodle differed
      from that of the other dogs. Examination of the zones of interest revealed that
      the cranial quadrant showed the greatest stiffness, whereas strength was highest
      at the medial site. The caudal cortex was less stiff and strong than the cranial
      cortex.

PMID- 22595312
TI  - Therapeutic peptide production in Drosophila.
AB  - Bioactive peptides are important therapeutic drugs, yet conventional methods of
      peptide synthesis are challenged to meet increasing demand. We developed a novel
      and efficient means of metabolic engineering: therapeutic peptide production in
      Drosophila and as a proof of concept, we demonstrate production of fully matured
      human insulin. This in vivo system offers an innovative means to produce valuable
      bioactive peptides for therapies, its inherent flexibility facilitates drug
      development, and its ease of producing fully processed peptides simplifies
      metabolic engineering of new peptide products.

PMID- 22595314
TI  - Surgeon-related variance: how much longer for its recognition?

PMID- 22595315
TI  - Management of life-threatening blunt head trauma in childhood-A case report.
AB  - INTRODUCTION: Traumatic head/brain injury (TBI) is a leading cause of death and
      life-long disability in children. The key to successful management of extradural
      haematoma is early recognition and evacuation. PRESENTATION OF CASE: We report
      the successful management of a child with life-threatening traumatic brain injury
      requiring timely surgical intervention outside of a specialist neurosurgical
      unit. DISCUSSION: Children with an operable injury have improved outcomes if
      their lesion is surgically evacuated within four hours. This can be challenging
      in regions located a significant distance from paediatric neurosurgical
      specialist centres. CONCLUSION: This case supports the recommendation for general
      surgeons maintaining the skill of burrhole evacuation of extradural haematomas.
      Whether this will remain feasible in the era of "super-specialisation" is
      questionable.

PMID- 22595313
TI  - Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe
      Crohn's disease: unexpected results of a randomised, double-blind placebo
      controlled trial.
AB  - OBJECTIVE: The authors tested whether the anti-interleukin (IL)-17A monoclonal
      antibody secukinumab was safe and effective for the treatment of active Crohn's
      disease. DESIGN: In a double-blind, randomised, placebo-controlled proof-of
      concept study, 59 patients with moderate to severe Crohn's disease (Crohn's
      Disease Activity Index (CDAI) >=220 to <=450) were assigned in a 2:1 ratio to
      2*10 mg/kg intravenous secukinumab or placebo. The primary end point, addressed
      by bayesian statistics augmented with historical placebo information, was the
      probability that secukinumab reduces the CDAI by >=50 points more than placebo at
      week 6. Ancillary analyses explored associations of 35 candidate genetic
      polymorphisms and faecal calprotectin response. RESULTS: 59 patients (39
      secukinumab, 20 placebo, mean baseline CDAI 307 and 301, respectively) were
      recruited. 18/59 (31%) patients discontinued prematurely (12/39 (31%)
      secukinumab, 6/20 (30%) placebo), 10/59 (17%) due to insufficient therapeutic
      effect (8/39 (21%) secukinumab, 2/20 (10%) placebo). Fourteen serious adverse
      events occurred in 10 patients (seven secukinumab, three placebo); 20 infections,
      including four local fungal infections, were seen on secukinumab versus none on
      placebo. Primary end point analysis estimated <0.1% probability (CDAI (SD) =33.9
      (19.7), 95% credible interval -4.9 to 72.9) that secukinumab reduces CDAI by >=50
      points more than placebo. Secondary area under the curve analysis (weeks 4-10)
      showed a significant difference (mean DeltaCDAI=49; 95% CI (2 to 96), p=0.043) in
      favour of placebo. Post hoc subgroup analysis showed that unfavourable responses
      on secukinumab were driven by patients with elevated inflammatory markers
      (CRP>=10 mg/l and/or faecal calprotectin>=200 ng/ml; mean DeltaCDAI=62; 95% CI (
      1 to 125), p=0.054 in favour of placebo). Absence of the minor allele of tumour
      necrosis factor-like ligand 1A was strongly associated with lack of response
      measured by baseline-adjusted changes in calprotectin at week 6 (p=0.00035
      Bonferroni-corrected). CONCLUSIONS: Blockade of IL-17A was ineffective and higher
      rates of adverse events were noted compared with placebo. CLINICAL TRIAL
      REGISTRATION: This trial was registered at ClinicalTrial.gov with the number
      NCT01009281.

PMID- 22595316
TI  - Biocide resistance of Candida and Escherichia coli biofilms is associated with
      higher antioxidative capacities.
AB  - BACKGROUND: Most clinical guidelines for the use of biocides have been developed
      for planktonic micro-organisms, but in nature, most micro-organisms live as
      surface-adherent communities or biofilms. AIM: To evaluate the effectiveness of
      commonly used biocides against Escherichia coli and Candida spp. in three
      distinct growth phases: planktonic, adhesion and biofilm. METHODS:
      Ultrastructural, architectural and cellular viability changes following a 5 min
      exposure to biocide were monitored by scanning electron microscopy and confocal
      laser scanning microscopy using fluorescent dyes. Comparative transcript
      expression of the antioxidants SOD1 and CAT1 in the planktonic and biofilm phases
      was evaluated using quantitative real-time polymerase chain reaction. FINDINGS:
      E. coli and Candida spp. in the planktonic phase were susceptible to all the
      tested biocides at the recommended concentrations. However, early adhesion and
      late biofilm phases of both were less susceptible to the biocides, and exceeded
      the recommended concentrations on several occasions. A short period of biocide
      exposure failed to fully eradicate the adherent microbial cells, and they
      recovered from the biocide challenge, forming biofilm on the biocide-treated
      surfaces. The biofilm phase showed higher expression of SOD1 and CAT1.
      CONCLUSION: The recommended concentrations of biocides for clinical disinfection
      in the hospital setting may not fully eradicate the adhesion or biofilm phases of
      E. coli and Candida spp. Higher antioxidative capacities in microbial biofilms
      may be responsible for the resistance of biofilms against clinical biocides.

PMID- 22595317
TI  - Reduction of misleading ("false") positive results in mammalian cell genotoxicity
      assays. II. Importance of accurate toxicity measurement.
AB  - In a previous publication, Fowler et al. [4] demonstrated that the seemingly high
      rate of false or misleading positive results obtained in in vitro cytogenesis
      assays for genotoxicity - when compared with in vivo genotoxicity or rodent
      carcinogenicity data - was greater when rodent cell lines were used that were
      also reported to have mutant or non-functional p53. As part of a larger project
      for improvement of in vitro mammalian cell assays, we have investigated the
      impact of different toxicity measures, commonly used in in vitro cytogenetic
      assays, on the occurrence of misleading positive results. From a list of 19
      chemicals that produce "false" positive results in in vitro mammalian cell assays
      [10], six substances that had given positive responses in CHO, CHL and TK6 cells
      [4], were evaluated for micronucleus induction in vitro, with different measures
      of toxicity for selection of the top concentration. The data show that estimating
      toxicity by relative cell count (RCC) or replication index (RI) consistently
      underestimates the toxicity observed by other measures (Relative Population
      Doubling, RPD, or Relative Increase in Cell Count, RICC). RCC and RI are more
      likely to lead to selection of concentrations for micronucleus scoring that are
      highly cytotoxic and thus could potentially lead to artefacts of toxicity being
      scored (elevated levels of apoptosis and necrosis), generating misleading
      positive results. These results suggest that a further reduction in the frequency
      of misleading positive results in in vitro cytogenetic assays can be achieved
      with this set of chemicals, by avoiding the use of toxicity measures that
      underestimate the level of toxicity induced.

PMID- 22595318
TI  - Interaction between the intestinal microbiota and host in Clostridium difficile
      colonization resistance.
AB  - Clostridium difficile infection (CDI) has become one of the most prevalent and
      costly nosocomial infections. In spite of the importance of CDI, our knowledge of
      the pathogenesis of this infection is still rudimentary. Although previous use of
      antibiotics is generally considered to be the sine qua non of CDI, the mechanisms
      by which antibiotics render the host susceptible to C. difficile are not well
      defined. In this review, we will explore what is known about how the indigenous
      microbiota acts in concert with the host to prevent colonization and virulence of
      C. difficile and how antibiotic administration disturbs host-microbiota
      homeostasis, leading to CDI.

PMID- 22595319
TI  - Prevalence of Kawasaki disease in young adults with suspected myocardial
      ischemia.
AB  - BACKGROUND: Up to 25% of patients with untreated Kawasaki disease (KD) and 5% of
      those treated with intravenous immunoglobulin will develop coronary artery
      aneurysms. Persistent aneurysms may remain silent until later in life when
      myocardial ischemia can occur. We sought to determine the prevalence of coronary
      artery aneurysms suggesting a history of KD among young adults undergoing
      coronary angiography for evaluation of possible myocardial ischemia. METHODS AND
      RESULTS: We reviewed the medical histories and coronary angiograms of all adults
      <40 years of age who underwent coronary angiography for evaluation of suspected
      myocardial ischemia at 4 San Diego hospitals from 2005 to 2009 (n=261). History
      of KD-compatible illness and cardiac risk factors were obtained by medical record
      review. Angiograms were independently reviewed for the presence, size, and
      location of aneurysms and coronary artery disease by 2 cardiologists blinded to
      the history. Patients were evaluated for number of risk factors, angiographic
      appearance of their coronary arteries, and known history of KD. Of the 261 young
      adults who underwent angiography, 16 had coronary aneurysms. After all clinical
      criteria were assessed, 5.0% had aneurysms definitely (n=4) or presumed (n=9)
      secondary to KD as the cause of their coronary disease. CONCLUSIONS: Coronary
      sequelae of KD are present in 5% of young adults evaluated by angiography for
      myocardial ischemia. Cardiologists should be aware of this special subset of
      patients who may benefit from medical and invasive management strategies that
      differ from the strategies used to treat atherosclerotic coronary artery disease.

PMID- 22595320
TI  - Newer concepts regarding adults with coronary artery aneurysms: are they all
      Kawasaki? Does it make a difference?

PMID- 22595321
TI  - Classification of older adults who have diabetes by comorbid conditions, United
      States, 2005-2006.
AB  - INTRODUCTION: Older adults who have diabetes vary widely in terms of comorbid
      conditions; these conditions help determine the risks and benefits of intensive
      glycemic control. Not all people benefit from intensive glycemic control. The
      objective of this study was to classify by comorbid conditions older American
      adults who have diabetes to identify those who are less likely to benefit from
      intensive glycemic control. METHODS: We used latent class analysis to identify
      subgroups of a nationally representative sample of community-dwelling older
      adults (aged 57-85 y) who have diabetes (n = 750). The subgroups were classified
      according to 14 comorbid conditions prevalent in the older population. Using the
      Akaike Information Criterion, the Bayesian Information Criterion (BIC), the
      sample-size adjusted BIC, and the chi(2) goodness-of-fit statistic, we assessed
      model fit. RESULTS: We found 3 distinct subgroups. Class 1 (63% of the sample)
      had the lowest probabilities for most conditions. Class 2 (29% of the sample) had
      the highest probabilities of cancer, incontinence, and kidney disease. Class 3
      (9% of the sample) had the highest probabilities (>90%) of congestive heart
      failure and myocardial infarction. Class 1 had only 0, 1, or 2 comorbid
      conditions, and both class 2 and class 3 had 6 or more comorbid conditions. The 5
      year death rates for class 2 (17%) and class 3 (33%) were higher than the rate
      for class 1 (9%). CONCLUSION: Older adults who have diabetes, cardiovascular
      disease, and 6 or more comorbid conditions may represent a subgroup of older
      adults who are less likely to benefit from intensive glycemic control.

PMID- 22595322
TI  - Asthma-related school absenteeism and school concentration of low-income students
      in California.
AB  - INTRODUCTION: Asthma is one of the leading causes of school absenteeism. Previous
      studies have shown that school absenteeism is related to family income of
      individual students. However, there is little research examining whether school
      absenteeism is related to school-level concentration of low-income students,
      independent of family income. The objective of this study was to examine whether
      the proportion of low-income students at a school was related to school
      absenteeism due to asthma. METHODS: Using data from the 2007 California Health
      Interview Survey, a population-based survey of California households, we examined
      the association between attending schools with high concentrations of low-income
      students and missing school because of asthma, adjusting for demographic
      characteristics, asthma severity, and health insurance status. Schools with high
      concentrations of low-income students were identified on the basis of the
      percentage of students participating in the free and reduced-price meal program,
      data publicly available from the California Department of Education. RESULTS:
      Students attending schools with the highest concentrations of low-income students
      were more likely to miss school because of asthma. Students from low-income
      families, younger students, those with more frequent asthma symptoms, or those
      taking prescription asthma medications also were more likely to miss school
      because of asthma. CONCLUSION: The use of school-level interventions to decrease
      school absenteeism due to asthma should be explored, especially in schools with
      high concentrations of low-income students. Potential interventions could include
      school-based asthma education and disease management or indoor and outdoor air
      pollution control.

PMID- 22595323
TI  - Evaluation of a weight management program for veterans.
AB  - INTRODUCTION: To improve the health of overweight and obese veterans, the
      Department of Veterans Affairs (VA) developed the MOVE! Weight Management Program
      for Veterans. The aim of this evaluation was to assess its reach and
      effectiveness. METHODS: We extracted data on program involvement, demographics,
      medical conditions, and outcomes from VA administrative databases in 4 Western
      states. Eligibility criteria for MOVE! were being younger than 70 years and
      having a body mass index (BMI, in kg/m(2)) of at least 30.0, or 25.0 to 29.9 with
      an obesity-related condition. To evaluate reach, we estimated the percentage of
      eligible veterans who participated in the program and their representativeness.
      To evaluate effectiveness, we estimated changes in weight and BMI using
      multivariable linear regression. RESULTS: Less than 5% of eligible veterans
      participated, of whom half had only a single encounter. Likelihood of
      participation was greater in women, those with a higher BMI, and those with more
      primary care visits, sleep apnea, or a mental health condition. Likelihood of
      participation was lower among those who were younger than 55 (vs 55-64), widowed,
      current smokers, and residing farther from the medical center (>=30 vs <30
      miles). At 6- and 12-month follow-up, participants lost an average of 1.3 lb (95%
      confidence interval [CI], -2.6 to -0.02 lb) and 0.9 lb (95% CI, -2.0 to 0.1 lb)
      more than nonparticipants, after covariate adjustment. More intensive treatment
      (>=6 encounters) was associated with greater weight loss at 12 months (-3.7 lb;
      95% CI, -5.1 to -2.3 lb). CONCLUSION: Few eligible patients participated in the
      program during the study period, and overall estimates of effectiveness were low.

PMID- 22595324
TI  - Physics and biology of neurodegenerative diseases.

PMID- 22595325
TI  - Visual distance cues modulate neuromagnetic auditory N1m responses.
AB  - OBJECTIVE: Auditory distance judgment relies on several acoustic cues and can be
      modulated by visual information. Sound intensity serves as one such cue as it
      decreases with increasing distance. In this magnetoencephalography (MEG)
      experiment, we tested whether N1m MEG responses, previously described to scale
      with sound intensity, are modulated by visual distance cues. METHODS: We recorded
      behavioral and MEG data from 15 healthy normal hearing participants. Noise bursts
      at different sound pressure levels were paired with synchronous visual cues at
      different distances. We hypothesized that noise paired with far visual cues will
      be represented louder and result in increased N1m amplitudes compared to a
      pairing with close visual cues. This might be based on a compensation of visually
      induced distance when processing loudness. RESULTS: Psychophysically, we observed
      no significant modulation of loudness judgments by visual cues. However, N1m MEG
      responses at about 100ms after stimulus onset were significantly stronger with
      distal compared to proximal visual cues in the left auditory cortex. CONCLUSIONS:
      Our results suggest an audio-visual interaction at an early stage in the left
      auditory cortex, possibly related to cue integration for auditory distance
      processing. SIGNIFICANCE: Sound distance processing could prove itself as a
      promising model system for the investigation of intra-modal and cross-modal
      integration principles.

PMID- 22595326
TI  - Effect of concentration and mode of intrathecal baclofen administration on soleus
      H-reflex in patients with muscle hypertonia.
AB  - OBJECTIVES: Assess spinal reflex excitability after increasing intrathecal
      baclofen (ITB) flow by manipulation of drug concentration and mode of
      administration. METHODS: The effect of concentration was assessed by comparing
      changes in H-reflex (H/M ratio) 1-6h after a 50MUg ITB bolus at 50MUg/ml
      concentration administered manually via lumbar puncture (LP, duration 1-2min,
      n=27) to a 50MUg bolus at 500MUg/ml concentration programmed through the pump and
      delivered via intrathecal catheter (IC, duration 10min) above simple continuous
      dose (25-100MUg/day, n=16). The effect of mode of administration was assessed by
      comparing peak changes in H/M ratio after 50MUg IC bolus above simple continuous
      dose (complex continuous mode, n=27) to simple continuous mode only (n=22) at
      equivalent daily doses (75-150MUg/day). RESULTS: H/M decrease was faster and
      overall greater after LP than IC bolus (mean 1-h 77% vs. 63%, p=0.012; 1-6h 91%
      vs. 82%, p<0.001, respectively). H/M ratio also decreased significantly more with
      complex (91%) than simple continuous mode of administration (78%, p=0.025).
      CONCLUSIONS: Lower ITB concentration and complex continuous mode of
      administration lead to greater decrease in H/M ratio. SIGNIFICANCE: Decreased
      spinal reflex excitability after adjustment of drug and pump parameters to
      increase ITB flow may result in better clinical response.

PMID- 22595327
TI  - Impact of ankle bracing on skill performance in recreational soccer players.
AB  - OBJECTIVE: To determine the effect of ankle braces on kicking accuracy, speed,
      and agility in competitive, nonelite soccer players. We hypothesized that the use
      of ankle bracing would significantly decrease performance in soccer-specific
      drills immediately after use but not after acclimation to the brace. DESIGN: A
      prospective randomized controlled trial. SETTING: University. PARTICIPANTS:
      Twenty healthy recreational adult soccer players (5 men and 15 women; mean age,
      23 +/- 4.8 years) without a history of lower extremity injury in the past 6
      months. All the subjects completed the study. METHODS: The subjects completed a
      set of performance measures (ie, accuracy shooting at a target, 40-yard dash,
      S180 degrees  run, and T test) with an McDavid 199 Lightweight ankle brace (test
      subjects) and without an ankle brace (control subjects) during 2 testing sessions
      spaced 7-10 days apart. Between the 2 testing sessions, the subjects wore the
      ankle brace on at least 4 occasions while participating in athletic activities to
      ensure that a learning effect occurred. MAIN OUTCOME MEASUREMENTS: Outcomes
      included kicking accuracy (accuracy shooting at a target) and speed and agility
      (time to complete a 40-yard dash, S180 degrees  run, and T test). RESULTS: No
      significant difference in performance was found for the accuracy in shooting at a
      target, 40-yard dash, S180 degrees  run, and T test (P > .05) with and without an
      ankle brace during a session and between sessions. CONCLUSIONS: Ankle braces did
      not significantly affect performance in speed, agility, or kicking accuracy in
      healthy, competitive, recreational soccer athletes.

PMID- 22595329
TI  - Protective effects of yacon (Smallanthus sonchifolius) intake on experimental
      colon carcinogenesis.
AB  - Yacon (Smallanthus sonchifolius), a tuberous root native to the Andean region of
      South America, contains high concentration of fructans with potential for colon
      cancer prevention. This study investigated the potential beneficial of yacon
      intake on colon carcinogenesis induced by 1,2-dimethylhydrazine (DMH) in male
      Wistar rats. After 4 weeks of DMH-initiation, groups were fed basal diet (G1 and
      G6) or basal diet containing dried extract of yacon root at 0.5% (G2), 1.0% (G3
      and G5) or a synbiotic formulation (G4) (1.0% yacon plus Lactobacillus casei at
      2.5 * 10(10)CFU per g diet) for 13 weeks. At week 20, a significant reduction in
      number and multiplicity of aberrant crypt foci (ACF) and in number of invasive
      adenocarcinomas was observed in the groups orally treated with 1.0% yacon (G3) or
      the synbiotic formulation (G4) (0.05<p<0.001). Tumor multiplicity (noninvasive
      plus invasive) was significantly lower in the group fed synbiotic formulation
      (p<0.02). A significant reduction in cell proliferation in colonic crypts and
      tumors and short chain fatty acids (SCFA) caecal contents was observed in the
      groups orally treated with 1.0% yacon (G3) or the synbiotic formulation (G4).
      Therefore, the findings this study indicate that yacon and yacon plus L. casei
      intake may reduce the development of chemically-induced colon cancer.

PMID- 22595328
TI  - Clinical outcomes analysis of conservative and surgical treatment of patients
      with clinical indications of prearthritic, intra-articular hip disorders.
AB  - OBJECTIVE: To describe outcomes of the conservative treatment of patients who had
      the clinical presentation of a prearthritic, intra-articular hip disorder,
      including acetabular labral tears, developmental hip dysplasia, and
      femoroacetabular impingement. DESIGN: Prospective observational clinical outcomes
      study. SETTING: Outpatient orthopedic clinic at a tertiary university hospital.
      PATIENTS: Patients presenting with prearthritic, intra-articular hip disorders
      were recruited. Fifty-eight consecutive patients were enrolled; 6 were lost to
      follow-up, and 52 subjects completed the study. METHODS: Patients were recruited
      on the basis of symptoms, distribution of pain, and the findings of a physical
      examination. Radiographic measurements of the hip were obtained for all subjects
      to describe the presence or absence and extent of deformity and/or
      osteoarthritis. All subjects completed a directed course of conservative
      treatment. After 3 months of conservative care, subjects with continued
      limitations, reduction of symptoms with a diagnostic intra-articular hip
      injection, and a surgically amenable lesion found on a magnetic resonance
      arthrogram proceeded to surgery. MAIN OUTCOME MEASUREMENTS: Numeric Pain Score (0
      10), Short Form-12, Modified Harris Hip Score, Western Ontario and McMaster
      Universities Osteoarthritis Index, Nonarthritic Hip Score, Baecke Questionnaire
      of Habitual Activity, and patient choice to have surgery. RESULTS: Fifty-eight
      patients (9 men and 49 women) with a mean age of 35 +/- 11 years (range, 18-50
      years) enrolled in the study. Fifty-two subjects completed the study. Twenty
      three subjects (44%) reported satisfaction with conservative care. Twenty-nine
      subjects (56%) chose to have surgery. Both groups demonstrated equally
      significant improvement (P value ranges: P = .03 to P = .0001) in all outcome
      measures from baseline to 1-year follow-up. Subjects who chose surgery had higher
      baseline activity scores compared with the conservative treatment group (P =
      .02). CONCLUSION: All subjects with signs and symptoms of prearthritic, intra
      articular hip disorders who were treated with conservative treatment alone and
      with conservative treatment followed by surgery demonstrated significant
      improvement in pain and functioning from baseline to 1 year. Forty-four percent
      of patients improved with conservative care alone, and 56% chose to have surgery
      after receiving conservative care. Persons with more active lifestyles were more
      likely to choose surgery. These data suggest that a trial of conservative
      management for persons with prearthritic, intra-articular hip disorders should be
      considered before engaging in surgical intervention.

PMID- 22595330
TI  - Plasma disposition and tissue depletion of chlortetracycline in the food
      producing animals, chickens for fattening.
AB  - Chickens were used to investigate plasma disposition of chlortetracycline after
      single IV (15 mg/kg) and multiple oral administration (60 mg/kg, 5 days) and
      residue depletion of chlortetracycline after multiple oral doses (60 mg/kg, 5
      days). Plasma and tissue samples were analyzed by HPLC. Mean elimination half
      lives in plasma were 7.96 and 13.15 h after IV and multiple oral administration.
      Maximum plasma concentration was 4.33 MUg/ml and the interval from oral
      administration until maximal concentration was 1.79 h. Oral bioavailability was
      17.76%. After multiple oral dose, mean kidney, liver and muscle tissue
      concentrations of chlortetracycline+4-epi-chlortetracycline of 835.3, 192.7, and
      126.3 MUg/kg, respectively, were measured 1 day after administration of the final
      dose of chlortetracycline. Chlortetracycline residues were detected in kidney and
      liver (205.4 and 81.7 MUg/kg, respectively), but not in muscle, 3 days after the
      end of chlortetracycline treatment. The mean chlortetracycline+4-epi
      chlortetracycline concentrations were below LOQ at 3 and 5 days after cessation
      of medication in muscle and liver, respectively. A withdrawal time of 3 days was
      necessary to ensure that the chlortetracycline residues were less than the
      maximal residue limits (MRLs) established by the European Union (100, 300, and
      600 MUg/kg in muscle, liver, and kidney, respectively).

PMID- 22595331
TI  - Homology of insect corpora allata and vertebrate adenohypophysis?
AB  - Animal species of various phyla possess neuroendocrine glands whose hormonal
      products regulate developmental and physiological mechanisms and directly impact
      behavior. Two examples, the corpora allata of insects and the vertebrate
      adenohypophysis have previously been regarded as analogous tissues that evolved
      independently from diffuse epidermal nerve nets of early metazoans. More recent
      developmental and functional studies accumulated evidence suggesting that the
      bilaterian nervous systems including its modern parts (e.g. pallium or cortex and
      mushroom bodies) and its neuroendocrine appendages (that are considered to be
      more ancient structures) possess a single evolutionary origin. The corpora allata
      of insects and the vertebrate adenohypophysis share a number of characteristics
      in respect of morphology, control of hormone release by RFamides, metabolites
      produced by closely related cytochrome P450 enzymes and gene expression during
      embryonic development. This review incorporates latest findings into an extensive
      description of similarities between insect corpora allata and vertebrate
      adenohypophysis that should encourage further studies about the onto- and
      phylogenetic origin of these neuroendocrine glands.

PMID- 22595332
TI  - Psychogenic gelastic seizures in a patient with hypothalamic hamartoma.
AB  - Gelastic seizures are classically associated with hypothalamic hamartoma. The
      most effective treatment for gelastic epilepsy is surgery, although confirming
      that a hypothalamic hamartoma is an epileptic lesion prior to surgical
      intervention is challenging. Here, we report the case of a patient with a
      hypothalamic hamartoma who was diagnosed with psychogenic non-epileptic gelastic
      seizures using video-EEG monitoring. [Published with video sequences].

PMID- 22595333
TI  - Alcohol septal ablation through a bare metal stent after rotative atherectomy: a
      complex procedure.
AB  - We report the case of a patient with severe malignant hypertrophic obstructive
      cardiomyopathy (HOCM) and calcified stenosis of the proximal and middle left
      anterior descending (LAD) coronary artery. We elected to treat his ischemic heart
      disease first. We performed angioplasty of the proximal and middle LAD, after
      rotative atherectomy, and implanted two bare metal stents. Thirty days later we
      treated his HOCM by alcohol septal ablation with catheterization of the first
      septal branch through the mesh of the bare metal stent implanted in the LAD. To
      our knowledge, this is the first documented report of such a procedure.

PMID- 22595335
TI  - Physical activity and psychosocial and mental health of older caregivers and non
      caregivers.
AB  - Few studies have been conducted on physical activity (PA) in older caregivers, a
      population at risk for mental and physical decline. To assess and compare PA, PA
      preferences, psychosocial determinants of PA, and mental health indicators
      between older non-exercising caregivers and non-caregivers. Caregivers (N = 24)
      and non-caregivers (N = 48) completed questionnaires and wore an accelerometer
      for 7 consecutive days. Few significant differences were noted in objectively
      measured or subjectively reported PA between caregivers and non-caregivers. Non
      caregivers reported greater social support to exercise from family members.
      Caregivers reported significantly greater anxiety, depression, stress, and
      negative health symptoms. Caregivers were significantly more likely to prefer
      exercise in 10-min bouts. Caregivers are in need of interventions to increase PA
      and health. Efforts to help caregivers participate in multiple shorter bouts of
      exercise during the day could be more effective than recommending one continuous
      30-minute bout.

PMID- 22595334
TI  - A meta-analysis on the impact of disease-specific education programs on health
      outcomes for patients with chronic obstructive pulmonary disease.
AB  - Disease-specific education programs have become an important factor in the
      treatment and care of chronic conditions, such as heart failure and diabetes
      mellitus. However, the effectiveness of these educational methods on chronic
      obstructive pulmonary disease (COPD) remains unclear. The objective of this meta
      analysis was to evaluate whether disease-specific education programs were
      beneficial to health-related quality of life (HRQoL) variables and other long
      term health outcomes in patients with COPD. Using electronic databases (PubMed,
      Cochrane Library, Science Direct, Chinese Biomedical Data System, China National
      Knowledge Infrastructure, and Wanfang Database) and individual searches
      (published and unpublished Chinese studies), we identified 12 randomized
      controlled trials (RCTs; English and/or Chinese) from 1991 to 2011. A meta
      analysis on these studies revealed a positive relationship between disease
      specific education programs and HRQoL scores (as measured by the St. George's
      Respiratory Questionnaire). Moreover, educational programs were associated with
      increased knowledge about COPD, improved disease management skills, inhaler
      adherence, and decreased COPD-related emergency department visits and hospital
      admissions, as well as long-term effects on improving COPD patients' health
      outcomes. Although significant effects were not detected across all HRQoL
      variables and health measures, our findings suggest that education programs have
      the potential to be a valuable intervention for COPD patients. Our results
      provide a foundation for future research in this area, which we recommend as
      including more rigorously designed, large, randomized studies.

PMID- 22595336
TI  - The role of caregiver burden in understanding African American custodial
      grandmothers.
AB  - African American grandmothers who parent their grandchildren often experience
      burden and altered health related to these responsibilities. However, little is
      known about how such burden reliably predicts physical and mental health, needs
      for information about services, needs for service and service use. Recruited from
      churches and community centers, 93 African American grandmothers who provided
      care for their grandchildren participated in this study. Hierarchical multiple
      regression was used to ascertain relationships between variables. Findings
      suggested that burden predicted needs for information about services, needs for
      service, service use, and physical health, but not mental health. In order to
      better understand grandmother caregivers' well-being and orientation to services,
      the present study suggests that the role of burden be centralized as a predictor
      of many parameters pertinent to grandparents raising their grandchildren.

PMID- 22595337
TI  - Protein aggregation and misfolding: good or evil?
AB  - Protein aggregation and misfolding have important implications in an increasing
      number of fields ranging from medicine to biology to nanotechnology  and material
      science. The interest in understanding this field has accordingly increased
      steadily over the last two decades. During this time the number of publications
      that have been dedicated to protein aggregation has increased exponentially,
      tackling the problem from several different and sometime contradictory
      perspectives. This review is meant to summarize some of the highlights that come
      from these studies and introduce this topical issue on the subject. The factors
      that make a protein aggregate and the cellular strategies that defend from
      aggregation are discussed together with the perspectives that the accumulated
      knowledge may open.

PMID- 22595338
TI  - Age estimation in children by measurement of open apices in tooth roots: Study of
      a Mexican sample.
AB  - The aim of this cross-sectional study was to test the accuracy of Cameriere's
      European formula for age assessment in a large sample of Mexican children. The
      accuracy of dental age estimation was defined as how closely real age, measured
      as the difference between chronological age (CA) and dental age (DA), could be
      predicted. Digitalized orthopantomographs of 502 Mexican children (254 girls and
      248 boys), aged between 5 and 15 years, were analyzed. The seven left permanent
      mandibular teeth were evaluated using Cameriere's method. Intra- and inter
      observer variability for this technique was tested on a small random sample.
      Dental age was estimated for each individual and compared with known
      chronological age. Accuracy was measured as the difference between known
      chronological age and dental age and tested for significance with the mean
      prediction error (ME). The standard deviation and 95% confidence interval of the
      mean difference were also calculated. ME was 0.63 years for girls and 0.52 years
      for boys. ME was found to be slightly overestimated by 0.10 years for girls, but
      was correctly estimated for boys with an accuracy of 0.00. In conclusion, this
      method is very useful and may be recommended for practical application both in
      clinical dentistry and forensic procedures on the Mexican population.

PMID- 22595339
TI  - How does subjective experience of pain relate to psychopathology among
      psychiatric patients?
AB  - OBJECTIVE: The study aimed to investigate to what extent general psychopathology
      is associated with subjective experience of pain in psychiatric outpatients
      without comorbidity with severe physical diagnosis and whether there are any
      differences in the experience of pain between genders or diagnoses. METHOD:
      Participants were 575 consecutive outpatients affected by mood disorder or
      anxiety disorder. Patients completed the West Haven-Yale Multidimensional Pain
      Inventory (WHYMPI) and the Symptom Checklist 90-Revised. RESULTS: Women had
      higher mean scores on the Global Severity Index (1.52+/-0.76 vs. 1.33+/-0.79),
      higher perception of negative responses from others (1.84+/-1.59 vs. 1.46+/-1.35)
      and higher perception of pain severity (3.31+/-1.73 vs. 2.88+/-1.63) than men.
      They also reported higher mean scores on the WHYMPI's General Activity (2.14+/
      0.98 vs. 1.93+/-0.95) and Household Chores (3.64+/-1.75 vs. 2.27+/-1.58) and
      lower mean scores on the Outdoor Work (1.24+/-1.26 vs. 1.87+/-1.51) dimension
      than men. Higher pain severity, more negative responses from others and higher
      household chores are predictors of higher psychopathology, while the general
      level of activity may be considered as a protective factor. CONCLUSIONS: Pain and
      its subjective experience play a central role in psychiatric disorders, and it is
      a great burden for patients and caregivers. Clinicians should pay more attention
      to recognize and adequately treat painful symptoms in patients with anxiety and
      depressive disorder.

PMID- 22595340
TI  - Appropriate reference gene selection for real-time PCR data normalization during
      rat mesenchymal stem cell differentiation.
AB  - Reverse transcription quantitative PCR (RT&mdash;qPCR) is one of the best methods
      for the study of mesenchymal stem cell (MSC) differentiation by gene expression
      analysis. This technique needs appropriate reference or housekeeping genes (HKGs)
      to normalize the expression of the genes of interest. In the present study the
      expression stability of six widely used HKGs including Actb, Btub, Hprt, B2m,
      Gusb and Tfrc was investigated during rat MSC differentiation into osteocytes,
      adipocytes and chondrocytes lineages using geNorm and NormFinder software.
      RT&mdash;qPCR data analyzed by geNorm revealed the different sets of suitable
      reference genes for each cell type. NormFinder also showed similar results.
      Analysis of the combined data of MSCs with each differentiated cell type revealed
      the considerable shift in expression of some reference genes during
      differentiation; for example Gusb and B2m were among the least stable genes in
      MSCs but the most stable in chondrocytes. Normalization of specific genes for
      each lineage by different reference genes showed considerable difference in their
      expression fold change. In conclusion, for the appropriate analysis of gene
      expression during rat MSC differentiation and also for monitoring differentiation
      procedures, it is better to consider precisely the reference gene stability and
      select suitable reference genes for each purpose.

PMID- 22595341
TI  - Administration of vitamin E prevents thymocyte apoptosis in murine sarcoma S180
      tumor bearing mice.
AB  - Many reports claimed that thymic involution occurred in tumor bearing host, which
      led to a reduction of proliferation in T cells and an impaired immune system. In
      this study, murine sarcoma S180 tumor cells were used to establish tumor model.
      There was distinct apoptosis in thymus of the S180 tumor bearing host after 3
      week tumor inoculation. High level reactive oxygen species generation was
      detected in thymocytes of S180 tumor bearers. Vitamin E, a potent antioxidant,
      was oral administrated to S180 tumor bearing mice in order to eliminate redundant
      ROS in the host and evaluate the effect against thymic apoptosis. Intact thymic
      structure and less apoptosis of thymocytes demonstrated that partial restoration
      of thymuses in S180 tumor bearing mice after 3-week VE treatment. Besides, VE
      treatment normalized ROS level, MDA level and SOD level of S180 tumor bearers.
      Thus, it could be concluded that thymic involution prevented by VE treatment in
      S180 tumor bearing mice was mainly due to inhibition of apoptosis in thymus and
      elimination of ROS over-production in the host.

PMID- 22595342
TI  - Enhanced productivity of electrospun polyvinyl alcohol nanofibrous mats using
      aqueous N,N-dimethylformamide solution and their application to lipase
      immobilizing membrane-shaped catalysts.
AB  - Electrospun polyvinyl alcohol (PVA) nanofibrous non-woven fabrics have been
      widely used for cell and enzyme immobilization. Enhancement of the productivity
      of the material will further enlarge the versatility of them. In this study, a
      mixture of water and N,N-dimethylformamide (DMF) was used as a solvent of PVA.
      The productivity defined as ([1 - (amount of polymer which did not come in
      contact with the collector)/(amount of polymer ejected from the needle for 30
      min)] * 100) of electrospun PVA fibers increased from 15 to 92% by increasing the
      content of DMF from 0 to 10 wt%. As a potential application of the electrospun
      PVA fibers prepared by the enhanced production system, we encapsulated
      Burkholderia cepacia (formerly, Pseudomonas cepacia) lipase in the fibers by
      including lipase powder in the PVA solution before electrospinning, and evaluated
      catalytic performance of the resultant fibrous catalysts in organic solvent. The
      lipase encapsulated in the PVA fibers produced from a solution of water and 10
      wt% DMF showed a 1.5-fold increase in initial reaction rate in the
      transesterification of (S)-glycidol and vinyl butyrate to produce (S)-glycidyl
      butyrate than that encapsulated in the PVA fibers obtained from the solvent
      without DMF, i.e., water. These findings demonstrate the practicality of the
      proposed system to enhance the productivity of electrospun PVA fibrous matrices
      for extended applications of the resultant fibers including the usage as carriers
      enclosing lipase for reactions in organic solvents.

PMID- 22595343
TI  - Establishment of evaluation method to determine effects of veterinary medicinal
      products on manure fermentation using small-scale composting apparatus.
AB  - To evaluate on a laboratory scale the influence of veterinary medicinal products
      (VMPs) excreted into feces on manure fermentation, we have developed an
      evaluation method that uses a small-scale composting apparatus. Each run is of
      approximately 3 kg scale and the operation can be conducted in an environmentally
      controlled laboratory. The main evaluation parameter is calorific value generated
      by aerobic fermentation. At the sulfadimethoxine (SDM) trial, the volume of CO(2)
      generated during fermentation and the disappearance of the inhibitory effect of
      immature manure on sprouting (using Komatsuna (Brassica rapa var. perviridis))
      were measured. In addition, DNA of 16S rRNA was extracted from a manure sample
      and subjected to denaturing gradient gel electrophoresis (DGGE). The results
      suggest that the presence of such VMPs in feces affected the microbial community
      in manure fermentation, and indicate that the evaluation method may be used as a
      standard method to evaluate the effect of VMPs on the microbial community. Using
      the method, we obtained data of the influence of five VMPs approved for
      stockbreeding in Japan on swine manure fermentation. Erythromycin (EM) affected
      the calorific value even at a relatively low concentration (105 mg/3 kg manure).
      In contrast, oxytetracycline hydrochloride (OTC), norfloxacin (NFLX), and tylosin
      tartrate (TS) had no effect at that concentration. These VMPs also affected the
      increase of fermentation temperature when added at high concentrations.

PMID- 22595344
TI  - Ethanol production from non-pretreated napiergrass through a simultaneous
      saccharification and fermentation process followed by a pentose fermentation with
      Escherichia coli KO11.
AB  - Efficient ethanol production from lignocellulosic napiergrass (Pennisetum
      purpureum Schumach) was examined by the combination of the simultaneous
      saccharification and fermentation (SSF) with commercial cellulase and
      Saccharomyces cerevisiae NBRC 2044 and subsequent pentose fermentation (PF) by
      Escherichia coli KO11. Under the optimized conditions, the combination of the SSF
      and PF processes resulted in the production of 144 mg g(-1) of ethanol from the
      non-pretreated napiergrass powder. The ethanol yield was 44.2% of the theoretical
      yield based on the hexose (37.5 g) and pentose (26.5 g) derived from 100 g of dry
      powdered napiergrass.

PMID- 22595345
TI  - Ca2+ signaling regulates ecmB expression, cell differentiation and slug
      regeneration in Dictyostelium.
AB  - Ca(2+) regulates cell differentiation and morphogenesis in a diversity of
      organisms and dysregulation of Ca(2+) signal transduction pathways leads to many
      cellular pathologies. In Dictyostelium Ca(2+) induces ecmB expression and stalk
      cell differentiation in vitro. Here we have analyzed the pattern of ecmB
      expression in intact and bisected slugs and the effect of agents that affect
      Ca(2+) levels or antagonize calmodulin (CaM) on this expression pattern. We have
      shown that Ca(2+) and CaM regulate ecmB expression and pstAB/pstB cell
      differentiation in vivo. Agents that increase intracellular Ca(2+) levels
      increased ecmB expression and/or pstAB and pstB cell differentiation, while
      agents that decrease intracellular Ca(2+) or antagonize CaM decreased it. In
      isolated slug tips agents that affect Ca(2+) levels and antagonize CaM had
      differential effect on ecmB expression and cell differentiation in the anterior
      versus posterior zones. Agents that increase intracellular Ca(2+) levels
      increased the number of ecmB expressing cells in the anterior region of slugs,
      while agents that decrease intracellular Ca(2+) levels or antagonize CaM activity
      increased the number of ecmB expressing cells in the posterior. We have also
      demonstrated that agents that affect Ca(2+) levels or antagonize CaM affect cells
      motility and regeneration of shape in isolated slug tips and backs and
      regeneration of tips in isolated slug backs. To our knowledge, this is the first
      study detailing the pattern of ecmB expression in regenerating slugs as well as
      the role of Ca(2+) and CaM in the regeneration process and ecmB expression.

PMID- 22595347
TI  - A simple assay of taurine concentrations in food and biological samples using
      taurine dioxygenase.
AB  - Taurine demonstrates various physiological functions and pharmacological actions.
      A successful application of taurine dioxygenase (EC 1.14.11.17) for taurine
      determination is described. The gene encoding taurine dioxygenase was cloned from
      Escherichia coli strain K-12, and the enzyme was used to determine taurine in
      commercially available beverages and some biological samples. The measured values
      obtained using the current method are close to the declared values with the
      precolumn derivatization ultra-performance liquid chromatography (UPLC)
      procedure. Taurine dioxygenase can be used for taurine determination in food
      control, biological research, and diagnoses based on urinary taurine
      concentration.

PMID- 22595348
TI  - Proceedings of the editorial board meeting of the American Journal of Cardiology
      on March 25, 2012.

PMID- 22595349
TI  - Utility of cardiac magnetic resonance imaging to differentiate cardiac
      sarcoidosis from arrhythmogenic right ventricular cardiomyopathy.
AB  - Some patients diagnosed with arrhythmogenic right ventricular cardiomyopathy
      (ARVC) are eventually found to have cardiac sarcoidosis (CS). Accurate
      differentiation between these 2 conditions has implications for immunosuppressive
      therapy and familial screening. We sought to determine whether cardiac magnetic
      resonance imaging (MRI) could be used to identify the characteristic findings to
      accurately differentiate between CS and ARVC. Consecutive patients with a
      diagnostic MRI scan indicating CS and/or ARVC constituted the cohort. All
      patients diagnosed with CS had histologic confirmation of sarcoidosis, and all
      patients with ARVC met the diagnostic task force criteria. The cardiac MRI data
      were retrospectively analyzed to identify possible differentiating
      characteristics. Of the patients, 40 had CS and 21 had ARVC. Those with CS were
      older and had more left ventricular scar. The presence of mediastinal
      lymphadenopathy or left ventricular septal involvement was seen exclusively in
      the patients with CS (p <0.001). A family history of sudden cardiac death was
      seen only in the ARVC group (p = 0.012). The right ventricular ejection fraction
      and ventricular volumes were also significantly different between the 2 groups.
      In conclusion, patients with CS have significantly different cardiac MRI
      characteristics than patients with ARVC. The cardiac volume, in addition to the
      degree and location of cardiac involvement, can be used to distinguish between
      these 2 disease entities. The presence of mediastinal lymphadenopathy and left
      ventricular septal scar favors a diagnosis of CS and not ARVC. Consideration of
      CS should be given if these MRI findings are observed during the evaluation for
      possible ARVC.

PMID- 22595346
TI  - The neural crest in cardiac congenital anomalies.
AB  - This review discusses the function of neural crest as they relate to
      cardiovascular defects. The cardiac neural crest cells are a subpopulation of
      cranial neural crest discovered nearly 30 years ago by ablation of premigratory
      neural crest. The cardiac neural crest cells are necessary for normal
      cardiovascular development. We begin with a description of the crest cells in
      normal development, including their function in remodeling the pharyngeal arch
      arteries, outflow tract septation, valvulogenesis, and development of the cardiac
      conduction system. The cells are also responsible for modulating signaling in the
      caudal pharynx, including the second heart field. Many of the molecular pathways
      that are known to influence specification, migration, patterning and final
      targeting of the cardiac neural crest cells are reviewed. The cardiac neural
      crest cells play a critical role in the pathogenesis of various human
      cardiocraniofacial syndromes such as DiGeorge, Velocardiofacial, CHARGE, Fetal
      Alcohol, Alagille, LEOPARD, and Noonan syndromes, as well as Retinoic Acid
      Embryopathy. The loss of neural crest cells or their dysfunction may not always
      directly cause abnormal cardiovascular development, but are involved secondarily
      because crest cells represent a major component in the complex tissue
      interactions in the head, pharynx and outflow tract. Thus many of the human
      syndromes linking defects in the heart, face and brain can be better understood
      when considered within the context of a single cardiocraniofacial developmental
      module with the neural crest being a key cell type that interconnects the
      regions.

PMID- 22595350
TI  - Molecular responses of brain endothelial cells to radiation in a mouse model.
AB  - Although most small arteriovenous malformations (AVM) are curable, over 90% of
      large lesions are untreatable with current surgery or radiosurgery. Endothelial
      cells (EC) are believed to be pivotal in the resulting vascular changes after AVM
      are irradiated, although their role is not fully understood. Elucidating the
      molecular effects of radiation on EC may allow development of new therapies that
      modulate the response of AVM to radiation. Cultured murine cerebral EC (bEnd.3)
      were exposed to a single 25 Gy dose of ionising radiation from a linear
      accelerator. Expression of the membrane proinflammatory and thrombotic molecules
      E-selectin, tissue factor (TF) and thrombomodulin (TM) were examined by
      immunofluorescent staining at times up to three weeks post irradiation. We found
      that E-selectin is significantly down regulated in the first 24 hours after
      irradiation. Later there is no significant difference in expression of this
      molecule between irradiated and non-irradiated groups. TM expression was
      significantly increased at all times, and the staining intensity of TF remained
      unchanged three weeks post irradiation. These results contribute to a greater
      understanding of the proinflammatory and thrombotic changes caused by irradiating
      normal brain EC.

PMID- 22595351
TI  - Isolated primary craniopharyngioma in the cerebellopontine angle.
AB  - Between January 2000 and January 2011, we diagnosed three patients with isolated
      craniopharyngioma in the cerebellopontine angle (CPA). Brain MRI revealed cystic
      lesions with various imaging characteristics, including hypointensity on T1
      weighted (T1W) images and hyperintensity on T2-weighted (T2W) images. The first
      patient's lesion showed rim enhancement after gadolinium administration. The
      second patient's lesion showed mixed signal intensity on both T1W and T2W images.
      The third patient's MRI showed a well-defined cystic lesion in the right CPA that
      compressed the brainstem. This lesion was hyperintense on T1W images and
      hypointense relative to cerebrospinal fluid on T2W images, and was peripherally
      enhanced after gadolinium administration. All three patients underwent surgical
      intervention through a suboccipital retrosigmoid craniotomy/craniectomy and
      lesions that did not adhere to adjacent tissues were removed completely.
      Histopathological examination confirmed the tumors to be adamantinomatous
      craniopharyngioma. The post-operative course was uneventful for all patients
      uneventful and no tumor recurrences were detected at the last follow-up. Primary
      CPA craniopharyngioma can be completely removed surgically, provided it does not
      densely adhere to vital structures.

PMID- 22595352
TI  - A single institution experience of the incidence of extracranial metastasis in
      glioma.
AB  - Glioblastoma multiforme (GBM) is the most common and aggressive subtype of all
      gliomas. The prognosis is poor but despite the aggressiveness of the tumour,
      extracranial metastasis of glioma is rare. Most documented cases of extracranial
      metastases of GBM involve leptomeningeal spread to the spine. In this clinical
      study we aim to review the incidence and location of extracranial metastasis of
      glioma from the Brain Tumor Database of the National Neuroscience Institute of
      Singapore, between September 2004 to October 2009. Four of 148 patients (2.7%)
      were identified, one of whom had pleomorphic xanthoastrocytoma (PXA) with scalp
      and spinal metastasis, suggestive of haematogenous rather than cerebrospinal
      fluid spread that has been described elsewhere. To our knowledge, there has been
      no published report of PXA with scalp metastasis or vertebral metastasis.

PMID- 22595353
TI  - A randomized, placebo-controlled pilot study of patients with spontaneous
      intraventricular haemorrhage treated with intraventricular thrombolysis.
AB  - Intraventricular hemorrhage (IVH) occurring after spontaneous intracerebral
      hemorrhage (ICH) is an independent risk factor for mortality. The use of
      intraventricular urokinase (Uk) to reduce intraventricular blood clot volume and
      improve outcome was investigated. Patients with IVH requiring external
      ventricular drainage were recruited and randomized into a double-blind placebo
      controlled study. Assessments of collected cerebrospinal fluid (CSF) haemoglobin
      (Hb) and serial CT scans were performed. The study outcomes were: infection
      rates, length of stay in the intensive care unit, survival, National Institutes
      of Health Stroke Scale score; and modified Rankin Scale scores. Our results
      showed an increase in both the drained CSF Hb concentration in patients treated
      with Uk compared to placebo and in the rate of resolution clot volume. No
      differences were found in the other outcome measures but there was a trend
      towards lowered mortality in the group treated with Uk. Therefore,
      intraventricular Uk resulted in faster resolution of IVH with no adverse events.

PMID- 22595354
TI  - Impact of maximal safe resection on the clinical outcome of adults with
      craniopharyngiomas.
AB  - Recent studies suggest that subtotal resection (STR) followed by adjuvant
      radiation therapy is an appealing alternative to gross total resection (GTR) for
      craniopharyngioma, as STR provides similar tumor control without the associated
      endocrinological and behavioral morbidity. We have examined the impact of maximal
      safe resection on the clinical outcome of patients with craniopharyngioma. A
      total of 90 patients underwent surgical resection of craniopharyngioma at a
      single institution between January 1995 and April 2009. Sixty-one patients
      underwent GTR alone, four underwent GTR followed by adjuvant radiotherapy, 15
      underwent STR alone, and 10 underwent partial removal followed by adjuvant
      radiotherapy. We analyzed and compared the clinical and endocrinological outcomes
      and radiological follow-up data of these patients. During the follow-up period,
      tumor recurrence following the initial resection occurred in 36 of 90 patients
      (40%). The repeat resection rate was higher in the STR group than the GTR group.
      Recurrence occurred in 20 of 61 patients (32.8%) from the GTR alone group, in 11
      of 15 patients (73.3%) from the STR alone group, and in five of 10 (50%) patients
      from the STR with adjuvant radiation, such as radiotherapy or stereotactic
      radiosurgery, group (p=0.030). Maximal safe resection of craniopharyngioma leads
      to excellent local control. STR with adjuvant radiation therapy does not assure
      preservation of endocrine function, although it provides better local control
      than STR alone.

PMID- 22595355
TI  - The acute effects of levetiracetam on nocturnal sleep and daytime sleepiness in
      patients with partial epilepsy.
AB  - This study investigated the effect of the novel antiepileptic drug levetiracetam
      (LEV) on sleep in eleven patients with partial epilepsy. At baseline and one week
      after therapy with LEV (1000 mg/day), patients underwent polysomnography (PSG)
      and the Multiple Sleep Latency Test (MSLT). Patients also rated their own degree
      of sleep disturbance and daytime sleepiness with the Athens Insomnia Scale (AIS)
      and the Epworth Sleepiness Scale (ESS). A group of 10 age- and gender-matched
      control participants were also included in the study. Patients had decreased
      total sleep time and increased daytime sleepiness compared to baseline, as
      evaluated by AIS subscales. Furthermore, LEV therapy significantly decreased the
      rapid eye movement sleep time and percentage as measured by PSG. Patients
      reported a significant increase in ESS score but did not exhibit changes in MSLT
      performance after LEV treatment. The study demonstrated that short-course LEV
      treatment can affect subjective sleep time and objective sleep architecture.
      Furthermore, LEV treatment affected subjective daytime sleepiness but did not
      influence objective mean daytime sleep latencies in patients with partial
      epilepsy.

PMID- 22595356
TI  - The role of cardiac disease parameters in predicting the results of Holter
      monitoring in patients with acute ischaemic stroke.
AB  - There is limited evidence supporting the routine use of Holter monitoring (HM) in
      patients with acute ischaemic stroke. This study aimed to assess the diagnostic
      yield of HM and determine whether any cardiac disease parameter(s) would permit
      more focused targeting of HM. We performed a retrospective evaluation of HM in
      patients with acute ischaemic stroke admitted to our hospital over a one-year
      period to assess diagnostic yield and whether certain cardiac disease parameters
      were correlated with HM results. The diagnostic yield was 9%, the number needed
      to screen was 11, and the cost to detect one clinically significant case was
      AUS$1,300. Apart from age, stratifying patients by cardiac disease parameters did
      not predict HM result. This strengthens the use of HM in all patients presenting
      with acute ischaemic stroke of unknown aetiology.

PMID- 22595357
TI  - Clinical outcomes of myelomeningocele defect closure over 10 years.
AB  - We report our surgical procedures for the closure of myelomeningocele defects. A
      retrospective analysis of 162 patients (74 male [45.7%], 88 female [54.3%]) with
      myelomeningocele was performed and the relationship between hydrocephalus,
      neurological status and the level and size of the myelomeningocele was described
      according to type of defect closure. Patients were divided into four groups
      according to the size of the defect, which was classified into ranges of 0-24
      cm(2), 25-39 cm(2), 40-60 cm(2) and >60 cm(2). Myelomeningocele occurred in the
      lumbar region in 114 patients (70%). The minimum defect size was 3*2 cm, and the
      maximum defect size was 15*15 cm (mean defect size=34.64 cm(2)). We found that
      primary closure can be performed on clean, small defects with an intact sac that
      contains cerebrospinal fluid and the neural placode. For defects larger than 25
      cm(2) that contained perforated sacculas, more soft tissue for well-vascularized
      coverage was required. Bilateral V-Y fasciocutaneous flaps are a good choice for
      immediate coverage of myelomeningocele defects.

PMID- 22595359
TI  - Sterostreins F-O, illudalanes and norilludalanes from cultures of the
      Basidiomycete Stereum ostrea BCC 22955.
AB  - Sterostreins F-O (1-10), 10 illudalanes and norilludalanes, were isolated from
      cultures of the Basidiomycete Stereum ostrea BCC 22955. Their structures were
      elucidated by analyses of the NMR spectroscopic and mass spectrometry data.
      Sterostreins M (8), N (9), and O (10) are pyridine-containing illudalanes.

PMID- 22595358
TI  - Hyperglycemia is independently associated with post-operative function loss in
      patients with primary eloquent glioblastoma.
AB  - The poor prognosis for patients with glioblastoma (GB) heightens the importance
      of maintaining function throughout treatment. Hyperglycemia has been linked to
      poor neurological outcomes following stroke, traumatic brain and spinal cord
      injury. We hypothesized this may also be true following the resection of GB. We
      assessed associations with post-operative function with the goal of identifying
      modifiable factors in the peri-operative period with a particular focus on blood
      glucose levels. Independent associations with worse post-operative function
      included: patient age, pre-operative motor deficit, deep tumor location, post
      operative motor deficit, and elevated mean peri-operative glucose. Interestingly,
      controlling for associated factors including dexamethasone dosing, patients with
      elevated peri-operative glucose levels were nearly twice as likely to have new
      post-operative neurological deficits. These results suggest, together with the
      broad literature supporting a role for hyperglycemia in neurological injury, that
      this may represent a modifiable factor in the peri-operative care of these
      patients.

PMID- 22595360
TI  - Acylated pregnane glycosides from Caralluma sinaica.
AB  - Caralluma sinaica is sold on local markets of Saudi Arabia for various health
      benefits however no phytochemical study has specifically been performed on this
      species. NMR and UHPLC-ESI-TOF-MS profilings of the ethanolic extract of the
      whole plant reveal a very complex phytochemical composition dominated by
      pregnanes. Detailed information on its constituents was obtained after isolation.
      Six pregnane glycosides were obtained and characterized based on the extensive
      spectroscopic analysis (including IR, 1H NMR, 13C NMR and MS data), in addition
      to ten known compounds (seven pregnanes and three flavonoids). The compounds were
      identified as 12beta-O-benzoyl-20-O-acetyl boucerin-3-O-6-deoxy-3-O-methyl-beta-D
      glucopyranosyl-(1-->4)-beta-D-cymaropyranosyl-(1-->4)-beta-D-cymaropyranoside,
      12beta-O-tigloyl-20-O-acetyl boucerin-3-O-beta-D-glucopyranosyl-(1-->4)-beta-D
      cymaropyranoside, 12beta-O-benzoyl-20-O-acetyl boucerin-3-O-beta-D-glucopyranosyl
      (1-->4)-beta-D-digitalopyranosyl-(1-->4)-beta-D-cymaropyranosyl-(1-->4)-beta-D
      cymaropyranoside, 12beta-O-benzoyl-20-O-acetyl boucerin-3-O-beta-D-glucopyranosyl
      (1-->4)-hevetopyranosyl-(1-->4)-beta-D-cymaropyranosyl-(1-->4)-beta-D
      cymaropyranoside, 12beta-O-benzoyl-20-O-tigloyl boucerin-3-O-beta-D
      glucopyranosyl-(1-->4)-beta-D-cymaropyranoside, 12beta-20-O-dibenzoyl boucerin-3
      O-beta-D-glucopyranosyl-(1-->4)-beta-D-cymaropyranosyl-(1-->4)-beta-D
      cymaropyranoside. Finally, the isolated compounds were evaluated for their
      quinone reductase induction.

PMID- 22595361
TI  - Characterisation of alleles of tomato light signalling genes generated by
      TILLING.
AB  - Targeting Induced Local Lesions IN Genomes (TILLING) combines chemical
      mutagenesis with high throughput screening to allow the generation of alleles of
      selected genes. In this study, TILLING has been applied to produce a series of
      mutations in genes encoding essential components of the tomato light signal
      transduction pathway in an attempt to enhance fruit nutritional quality. Point
      mutations to DEETIOLATED1 (DET1), which is responsible for the high pigment2
      (hp2) tomato mutant, resulted in elevated levels of both carotenoid and
      phenylpropanoid phytonutrients in ripe fruit, whilst immature fruit showed
      increased chlorophyll content, photosynthetic capacity and altered fruit
      morphology. Furthermore, genotypes with mutations to the UV-DAMAGED DNA BINDING
      PROTEIN 1 (DDB1), COP1 and COP1like were also characterised. These genotypes
      largely did not display phenotypes characteristic of mutation to light signalling
      components but their characterisation has enabled interrogation of structure
      function relationships of the mutated genes.

PMID- 22595363
TI  - Galantamine administration in chronic post-stroke aphasia.
AB  - BACKGROUND: To investigate the influence of galantamine on linguistic function,
      any associated factors in patients with chronic post-stroke aphasia were
      analysed. METHODS: 45 patients younger than 75 years with chronic aphasia (>=1
      year since onset) were prospectively enrolled in the study. Language testing was
      performed at weeks 0 and 16. Initial galantamine dose was 8 mg/day for 4 weeks,
      and 16 mg/day for the following 12 weeks. Efficacy was evaluated by the sum of
      four domains (spontaneous speech, comprehension, repetition and naming) on the
      aphasia quotient (AQ) of the Western Aphasia Battery from baseline (AQ1) to
      endpoint (AQ2). Patients were considered as 'responding' if the increase in AQ
      was >=20. RESULTS: Mean age was 60.4 years (22-74) and 14 patients were female.
      Mean duration of aphasia was 2.2+/-1.5 years. There was a significant increase in
      the total AQ score in the galantamine group (n=23, 48.5-57.0 percentile; p=0.007)
      but not in the control group (n=22, 54.3-54.9 percentile; p=0.308). The AQ2 score
      was independently associated with AQ1, galantamine administration and Mini-Mental
      State Examination (MMSE) score in multiple linear regression models. With the
      galantamine group, the good responders (vs poor responders) had a higher level of
      education (p=0.048), higher baseline MMSE score (p=0.009) and a subcortical
      dominant pattern (p=0.030). After adjusting for potential variables, subcortical
      dominant lesion was the independent determinant for galantamine responsiveness
      (OR 30.3; 95% CI 1.1 to 805.9, p=0.041). CONCLUSION: Administration of
      galantamine had a beneficial effect on chronic post-stroke aphasia, and was more
      prominent in subcortical dominant lesions.

PMID- 22595364
TI  - Transcriptomic profile of host response in mouse brain after exposure to plant
      toxin abrin.
AB  - Abrin toxin is a plant glycoprotein, which is similar in structure and properties
      to ricin and is obtained from the seeds of Abrus precatorius (jequirity bean).
      Abrin is highly toxic, with an estimated human fatal dose of 0.1-1 MUg/kg, and
      has caused death after accidental and intentional poisoning. Abrin is a potent
      biological toxin warfare agent. There are no chemical antidotes available against
      the toxin. Neurological symptoms like delirium, hallucinations, reduced
      consciousness and generalized seizures were reported in human poisoning cases.
      Death of a patient with symptoms of acute demyelinating encephalopathy with
      gastrointestinal bleeding due to ingestion of abrin seeds was reported in India.
      The aim of this study was to examine both dose and time-dependent transcriptional
      responses induced by abrin in the adult mouse brain. Mice (n=6) were exposed to 1
      and 2 LD50 (2.83 and 5.66 MUg/kg respectively) dose of abrin by intraperitoneal
      route and observed over 3 days. A subset of animals (n=3) were sacrificed at 1
      and 2 day intervals for microarray and histopathology analysis. None of the 2
      LD50 exposed animals survived till 3 days. The histopathological analysis showed
      the severe damage in brain and the infiltration of inflammatory cells in a dose
      and time dependent manner. The abrin exposure resulted in the induction of rapid
      immune and inflammatory response in brain. Clinical biochemistry parameters like
      lactate dehydrogenase, aspartate aminotransferase, urea and creatinine showed
      significant increase at 2-day 2 LD50 exposure. The whole genome microarray data
      revealed the significant regulation of various pathways like MAPK pathway,
      cytokine-cytokine receptor interaction, calcium signaling pathway, Jak-STAT
      signaling pathway and natural killer cell mediated toxicity. The comparison of
      differential gene expression at both the doses showed dose dependent effects of
      abrin toxicity. The real-time qRT-PCR analysis of selected genes supported the
      microarray data. This is the first report on host-gene response using whole
      genome microarray in an animal model after abrin exposure. The data generated
      provides leads for developing suitable medical counter measures against abrin
      poisoning.

PMID- 22595362
TI  - The LaLiMo Trial: lamotrigine compared with levetiracetam in the initial 26 weeks
      of monotherapy for focal and generalised epilepsy--an open-label, prospective,
      randomised controlled multicenter study.
AB  - BACKGROUND: Of the newer antiepileptic drugs, lamotrigine (LTG) and levetiracetam
      (LEV) are popular first choice drugs for epilepsy. The authors compared these
      drugs with regard to their efficacy and tolerability in the initial monotherapy
      for epilepsy. METHODS: A randomised, open-label, controlled, parallel group,
      multicenter trial was conducted to test the superiority of the LEV arm over the
      LTG arm. The primary endpoint was the rate of seizure-free patients in the first
      6 weeks (two-sided Fisher's exact test, alpha=0.05, intent-to-treat set).
      Furthermore, efficacy, tolerability and quality of life were evaluated. The
      authors included 409 patients aged >=12 years with newly diagnosed focal or
      generalised epilepsy defined by either two or more unprovoked seizures or one
      first seizure with high risk for recurrence. Patients were titrated to 2000
      mg/day of LEV or 200 mg/day of LTG reached on day 22 or 71, respectively. Two
      dose adjustments by 500/50 mg were allowed. RESULTS: The proportions of seizure
      free patients were 67.5% (LEV) versus 64.0% (LTG) 6 weeks after randomisation
      (p=0.47), and 45.2% (LEV) versus 47.8% (LTG) during the whole treatment period of
      26 weeks. The HR (LEV vs. LTG) for seizure-free time was 0.86 (95% CI, 0.61 to
      1.22). Adverse events occurred in 74.5% (LEV) versus 70.6% (LTG) of the patients
      (p=0.38). Adverse events associated with study discontinuation occurred in 17/204
      (LEV) versus 8/201 (LTG) patients (p=0.07). CONCLUSIONS: There were no
      significant differences with regard to efficacy and tolerability of LEV and LTG
      in newly diagnosed focal and generalised epilepsy despite more rapid titration in
      the LEV arm. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier
      NCT00242606.

PMID- 22595365
TI  - Mechanistic investigations on the etiology of Risperdal((r)) Consta((r))-induced
      bone changes in female Wistar Hannover rats.
AB  - RISPERDAL((r)) CONSTA((r)) is a long-acting, intramuscular formulation of
      risperidone microspheres for the biweekly treatment of schizophrenia and other
      psychiatric disorders. In a 24-month carcinogenicity study male and female Wistar
      Hannover rats received RISPERDAL((r)) CONSTA((r)) by intramuscular injection at
      dosages of 5 or 40 mg/kg once every 2 weeks. Bone changes described as
      "osteodystrophy" were observed by routine microscopic examination at 40 mg/kg in
      the sternum of female rats after 12 months, and in the sternum and stifle joint
      of both male and female rats after 24 months of treatment, respectively. To
      investigate the etiology of these bone changes, a 12-month mechanistic study was
      conducted in female Wistar Hannover rats at dosages of 5, 20 and 40 mg/kg once
      every 2 weeks. In addition to routine parameters, this study included bone
      markers, hormone measurements, and peripheral quantitative computed tomography
      (pQCT) and dual-energy X-ray absorptiometry (DXA) bone density measurements. It
      revealed a treatment-related reduction in metaphyseal trabecular bone density of
      the femur and tibia at 20 and 40 mg/kg, which was evident in the tibia from Week
      13 of treatment onwards. There was no convincing evidence for any of the modes of
      action known to underlie trabecular bone loss in rats including renal,
      nutritional, or hepatic osteodystrophy, estrogen deficiency, hyperthyroidism or
      glucocorticoid excess. It is hypothetized that prolonged hyperprolactinemia
      accompanied by an increase in parathyroid hormone-related protein (PTHrP) levels
      and a slight hypoestrogenic state could have caused the reduced trabecular bone
      density in RISPERDAL((r)) CONSTA((r))-treated rats. The relevance of this finding
      in terms of human risk is unknown.

PMID- 22595366
TI  - Neurodevelopmental and behavioral toxicity via lactational exposure to the sum of
      six indicator non-dioxin-like-polychlorinated biphenyls (?6 NDL-PCBs) in mice.
AB  - In this study, the neurobehavioral toxicity of lactational exposure to a
      representative mixture of the six indicator non-dioxin-like-polychlorinated
      biphenyls (?6 NDL-PCBs 28, 52, 101, 138, 153 and 180) found in contaminated fish
      matrices were assessed in neonatal (postnatal day 0) to adult (postnatal day 275)
      mice. Thus, a battery of developmental, behavioral and cognitive tests was
      performed. The performance of mice whose mothers were orally exposed to ?6 NDL
      PCBs at environmental doses of 1 ng/kg, 10 ng/kg or 100 ng/kg was compared to
      that of mice whose mothers were orally exposed to vehicle. Our results showed
      that neonatal offspring mice exposed to ?6 NDL-PCBs through lactation exhibited
      significantly longer turning reflexes on postnatal days 7 and 9 (p=0.001,
      p=0.002, respectively) at 100 ng/kg and showed a reduction in their general
      activity at 1 ng/kg (p=0.002) and 10 ng/kg (p=0.001) compared to controls.
      However, these developmental alterations were sex-dependent; only the female
      reflexes and male locomotor activity were affected. These disturbances were
      transient, and they disappeared with age. In addition, the males' visuomotor
      integration was also altered at the doses of 1 ng/kg (p=0.02) and 100 ng/kg
      (p=0.004), as revealed by the WESPOC test. Nevertheless, lactational exposure to
      ?6 NDL-PCBs (1-100 ng/kg) resulted in persistent disturbances despite a long post
      weaning period; the exposed mice exhibited anxious behavior that was detected at
      more progressive life stages, i.e., at postnatal days 40 and 160, using an
      elevated plus maze and the light/dark choice test, respectively. This persistent
      anxious behavior could be related to the overexpression of RyR3 in the cerebellum
      via the disruption of calcium signaling in the neurons. We found no differences
      in the offspring mice with regard to their cognitive function and mood or mRNA
      neurotransmitter receptor gene expression in several brain areas, including 5
      HT(1A), MOR1 and GABA(Aalpha1), suggesting the absence of adverse effects of
      postnatal exposure to ?6 NDL-PCBs under these conditions. Therefore, our results
      suggest that regular consumption of contaminated fish matrices by lactating women
      could be detrimental to the neurodevelopment of their newborns.

PMID- 22595367
TI  - Developmental cigarette smoke exposure: kidney proteome profile alterations in
      low birth weight pups.
AB  - The Brenner hypothesis states that a congenital reduction in nephron number
      predisposes to adult-onset hypertension and renal failure. The reduction in
      nephron number induced by proportionally smaller kidney mass may predispose
      offspring to glomerular hyperfiltration with maturity onset obesity.
      Developmental cigarette smoke exposure (CSE) results in intrauterine growth
      retardation with a predisposition to obesity and cardiovascular disease at
      maturity. Utilizing a mouse model of 'active' developmental CSE (gestational day
      [GD] 1-postnatal day [PD] 21; cotinine>50 ng/mL) characterized by persistently
      smaller offspring with proportionally decreased kidney mass, the present study
      examined the impact of developmental CSE on the abundance of proteins associated
      with cellular metabolism in the kidney. Following cessation of CSE on PD21,
      kidney tissue was collected from CSE and Sham exposed pups for 2D-SDS-PAGE based
      proteome profiling with statistical analysis by partial least squares
      discriminant analysis (PLS-DA) with affected molecular pathways identified by
      ingenuity pathway analysis. Proteins whose expression in the kidney were affected
      by developmental CSE belonged to the inflammatory disease, cell to cell
      signaling/interaction, lipid metabolism, small molecule biochemistry, cell cycle,
      respiratory disease, nucleic acid and carbohydrate metabolism networks. The
      present findings indicate that developmental CSE alters the kidney proteome. The
      companion paper details the liver proteome alterations in the same offspring.

PMID- 22595368
TI  - Two weeks of buspirone protects against posthypoxic ventilatory pauses in the
      C57BL/6J mouse strain.
AB  - The purpose was to determine if 2 weeks of buspirone suppressed post-hypoxic
      breathing instability and pauses in the C57BL/6J (B6) mouse. Study groups were
      vehicle (saline, n=8), low-dose (1.5 mg/kg, n=8), and high-dose buspirone (5.0
      mg/kg, n=8). Frequency, measured by plethysmography, was the major metric, and a
      pause defined by breathing cessation >2.5 times the average frequency. Mice were
      tested after 16 days of ip injections of vehicle or drug. On day 17, 4 mice in
      each group were tested after buspirone and the 5-HT(1A) receptor antagonist, 4
      iodo-N-{2-[4-(methoxyphenyl)-1-piperazinyl] ethyl}-N-2-pyridinyl-benzamide (p
      MPPI, 5 mg/kg). A post-hypoxic pause was present in 6/8 animals given vehicle and
      1/16 animals given buspirone at either dose, but always present (8/8) with p
      MPPI, regardless of buspirone dose. Post-hypoxic frequency decline was blunted by
      buspirone (-10% vehicle vs. -5% at both doses) and restored by p-MPPI;
      ventilatory stability as described by the coefficient of variation which was
      reduced by buspirone (p<0.04) was increased by p-MPPI (0.01). In conclusion,
      buspirone administration after 2 weeks acts through the 5-HT(1A) receptor to
      reduce post-hypoxic ventilatory instability in the B6 strain.

PMID- 22595369
TI  - The heme oxygenase-carbon monoxide system in the regulation of cardiorespiratory
      function at high altitude.
AB  - Pulmonary arterial hypertension is one of the most serious pathologies that can
      affect the 140 million people living at altitudes over 2500 m. The primary
      emphasis of this review is pulmonary artery hypertension in mammals (sheep and
      llamas) at high altitude, with specific focus on the heme oxygenase and carbon
      monoxide (HO-CO) system. We highlight the fact that the neonatal llama has
      neither pulmonary artery hypertension nor pulmonary vascular remodeling in the
      Andean altiplano. These neonates have an enhanced HO-CO system function,
      increasing the HO-1 protein expression and CO production by the pulmonary
      vessels, when compared to llamas raised at low altitude, or neonatal sheep raised
      at high altitude. The neonatal sheep has high altitude pulmonary artery
      hypertension in spite of enhancement of the NO system, with high eNOS protein
      expression and NO production by the lung. The gasotransmitters NO and CO are
      important in the regulation of the pulmonary vascular function at high altitudes
      in both high altitude acclimatized species, such as the sheep, and high altitude
      adapted species, such as the llama.

PMID- 22595370
TI  - Age-related retinal inflammation is reduced by 670 nm light via increased
      mitochondrial membrane potential.
AB  - The mitochondrial theory of aging argues that oxidative stress, caused by
      mitochondrial DNA mutations, is associated with decreased adenosine triphosphate
      (ATP) production leading to cellular degeneration. The rate of this degradation
      is linked to metabolic demand, with the outer retina having the greatest in the
      body, showing progressive inflammation, macrophage invasion, and cell loss,
      resulting in visual decline. Mitochondrial function shifts in vitro after 670-nm
      light exposure, reducing oxidative stress and increasing ATP production. In vivo,
      it ameliorates induced pathology. Here, we ask whether 670 nm light shifts
      mitochondrial function and reduces age-related retinal inflammation. Aged mice
      were exposed to only five 90-second exposures over 35 hours. This significantly
      increased mitochondrial membrane polarization and significantly reduced
      macrophage numbers and tumor necrosis factor (TNF)-alpha levels, a key
      proinflammatory cytokine. Three additional inflammatory markers were assessed;
      complement component 3d (C3d), a marker of chronic inflammation and calcitonin,
      and a systemic inflammatory biomarker were significantly reduced. Complement
      component 3b (C3b), a marker of acute inflammation, was not significantly
      altered. These results provide a simple route to combating inflammation in an
      aging population with declining visual function and may be applicable to clinical
      conditions where retinal inflammation is a key feature.

PMID- 22595372
TI  - Alzheimer's disease: biological aspects, therapeutic perspectives and diagnostic
      tools.
AB  - Alzheimer's disease (AD) is the most common form of dementia among older people.
      Dementia is an irreversible brain disorder that seriously affects a person's
      ability to carry out daily activities. It is characterized by loss of cognitive
      functioning and behavioral abilities, to such an extent that it interferes with
      the daily life and activities of the affected patients. Although it is still
      unknown how the disease process begins, it seems that brain damage starts a
      decade or more before problems become evident. Scientific data seem to indicate
      that changes in the generation or the degradation of the amyloid-b peptide
      (Abeta) lead to the formation of aggregated structures that are the triggering
      molecular events in the pathogenic cascade of AD. This review summarizes some
      characteristic features of Abeta misfolding and aggregation and how cell damage
      and death mechanisms are induced by these supramolecular and toxic structures.
      Further, some interventions for the early diagnosis of AD are described and in
      the last part the potential therapeutic strategies adoptable to slow down, or
      better block, the progression of the pathology are reported.

PMID- 22595371
TI  - The MAPT p.A152T variant is a risk factor associated with tauopathies with
      atypical clinical and neuropathological features.
AB  - Microtubule-associated protein tau (MAPT) mutations have been shown to underlie
      frontotemporal dementia and a variety of additional sporadic tauopathies. We
      identified a rare p.A152T variant in MAPT exon 7 in two (of eight) patients with
      clinical presentation of parkinsonism and postmortem finding of neurofibrillary
      tangle pathology. Two siblings of one patient also carried the p.A152T variant,
      and both have progressive cognitive impairment. Further screening identified the
      variant in two other cases: one with pathologically confirmed corticobasal
      degeneration and another with the diagnosis of Parkinson's disease with dementia.
      The balance of evidence suggests this variant is associated with disease, but the
      very varied phenotype of the cases with the mutation is not consistent with it
      being a fully penetrant pathogenic mutation. Interestingly, this variation
      results in the creation of a new phosphorylation site that could cause reduced
      microtubule binding. We suggest that the A152T variant is a risk factor
      associated with the development of atypical neurodegenerative conditions with
      abnormal tau accumulation.

PMID- 22595373
TI  - Patterns of life events preceding the suicide in rural young Chinese: a case
      control study.
AB  - BACKGROUND: Previous studies on the Chinese suicide found some life events prior
      to the suicide different from those in the West, but there is a lack of summary
      of the Chinese life event patterns to better understand the effects of the social
      structure on Chinese suicide. AIM: We tried to identify the life events that
      precede the Chinese rural youth suicides and compare them with what are found in
      the West, so as to find the patterns that are particularly true in the Chinese
      culture contexts. METHODS: Suicide cases were investigated with a psychological
      autopsy study in rural China, and local community living controls were also
      interviewed with the same protocol. RESULTS: We collapsed 64 negative life events
      into six categories: (1) Marriage/Love, (2) Family/Home, (3) Work/Business, (4)
      Health/Hospital, (5) Law/Legal, (6) Friend/Relationship. About 92.3% of the
      suicides studied had experienced at least one type of negative life events. The
      three most common negative life events categories in the past one year were
      Family/Home (60.7%), Health/Hospital (53.8%) and Marriage/Love (51.3%) in the
      rural young suicide victims. CONCLUSIONS: Among the negative life events, those
      related to family relations, love affairs, and marital issues were most likely to
      precede a suicide of rural suicides in China, and it is especially true of rural
      young women. Family is an important social institution in rural China for suicide
      prevention efforts.

PMID- 22595374
TI  - Neurocognitive effects after brief pulse and ultrabrief pulse unilateral
      electroconvulsive therapy for major depression: a review.
AB  - BACKGROUND: Neurocognitive functioning is well known to be affected after ECT.
      However quantified data about the severity of the cognitive impairment after
      ultrabrief pulse and brief pulse ECT are limited, which makes it hard to judge
      its clinical relevance. METHODS: To review all prospective studies using right
      unilateral (ultra) brief pulse index electroconvulsive therapy published up until
      February 2011 which used at least one instrument for cognitive assessment before
      and after ECT. The severity and persistence of neurocognitive side effects
      immediately (one to seven days post ECT), between one and six months and after
      six months post ECT were assessed by calculating effect sizes using Cohen's d.
      RESULTS: Ten studies fulfilled the inclusion criteria and provided detailed
      information to compute effect sizes. The results indicate loss of
      autobiographical memory and impairment of verbal fluency, anterograde verbal and
      non-verbal memory immediately after brief pulse RUL ECT. To a lesser extent
      impairment of working memory and reduced speed of processing is found.
      Autobiographical memory is the only domain still being impaired between one and
      six months post ECT, but improved in this period. Verbal fluency normalized to
      baseline performance between one and six months post ECT whereas anterograde
      verbal and non-verbal memory normalized or even improved. Speed of processing
      improved within six months after ECT. Long-term data on these cognitive domains
      were not available. Based on two of the ten included studies the results suggest
      that ultrabrief pulse RUL ECT causes less decline in autobiographical and
      anterograde memory after ECT than brief pulse RUL ECT. LIMITATIONS: This review
      may be limited because of the small number of included studies and due to
      unreliable effect sizes. Furthermore, few data were available for non-memory
      domains and cognitive functioning after six months. CONCLUSIONS: Loss of
      autobiographical memory is still present between one and six months after
      unilateral brief pulse ECT. Ultrabrief pulse RUL ECT shows less decline in
      autobiographical memory. Other neurocognitive impairments after brief pulse RUL
      ECT seem to be transient.

PMID- 22595375
TI  - Cytogenetic evaluation: a primer for pediatric nurse practitioners.
AB  - Patients with genetic disorders require specific types of cytogenetic testing for
      accurate diagnosis and prognosis followed by prompt treatment. This primer will
      serve as a guide for pediatric nurse practitioners on the use of various
      cytogenetic testing for the diagnosis of genetic disorders. Knowledge of the
      latest cytogenetic technologies will facilitate diagnosis and counseling related
      to genetic abnormalities such as inherited disorders, mental retardation,
      developmental delay, and autism. This reference will enable pediatric nurse
      practitioners to help identify patients with various inherited genetic disorders
      and provide subsequent monitoring and treatment. 

PMID- 22595376
TI  - Transnasal endoscopic surgery for benign orbital tumors.
AB  - Two cases of orbital tumor are presented, and the surgical technique by means of
      an endoscopic transnasal approach is discussed. In Case 1, a non-vascular, benign
      tumor was located inside the orbit, and it was able to be completely removed,
      without any complications. The tumor in Case 2 was also located inside the orbit,
      but it was determined to be a hemangioma based on the intraoperative pathology.
      To avoid eye complications arising from performance of the surgery in the
      presence of bleeding, it was decided to widely open the orbital lamina papyracea
      and periosteum, and perform only orbital decompression. The eye symptoms
      disappeared in both patients. Endoscopic transnasal surgery is indicated for
      benign orbital tumors that are medially located in the orbit. It can be thought
      that the eye symptoms can be alleviated by avoiding orbital pressure, regardless
      of whether-based on the intraoperative pathology-the tumor is completely removed
      or not.

PMID- 22595377
TI  - Evaluation of "Open Essence" odor-identification test card by application to
      healthy volunteers.
AB  - OBJECTIVE: In the United States and European countries, the University of
      Pennsylvania Smell Identification Test (UPSIT), the Quick Smell Identification
      Test (Q-SIT), a shorter version of the UPSIT, and "Sniffin' Sticks" are widely
      used for testing olfaction. The odor stick identification test for Japanese (OSIT
      J) has been manufactured in Japan. This was followed by the development of "Open
      Essence," consisting of cards that make use of sealed odorants. This study
      examined the usefulness of Open Essence in young volunteers with normal
      olfaction. METHOD: The participants were 176 medical students in their clinical
      clerkships at the Department of Otolaryngology, Kochi Medical School Hospital.
      There were 111 males and 65 females, with a median age of 24 years (range 22-42
      years). The olfactory function of all participants was confirmed as normal by
      screening with T&T olfactometry. Before beginning Open Essence, the subjects were
      asked to answer a questionnaire on their olfaction and habits. RESULTS: Females
      had significantly better smell identification than males. Of the 12 odorants,
      "perfume" and "cooking gas" were difficult to identify, because perfume involves
      different imagery and the compounds that give the smell of gas are readily
      volatilized. In contrast, all participants recognized "curry" and "menthol,"
      probably because they are received as both somatosensory stimuli and smell.
      CONCLUSIONS: These results suggest that, with improvement, Open Essence might be
      used for testing olfaction in Japanese subjects.

PMID- 22595378
TI  - The prediction of recurrent preterm birth in patients on 17-alpha
      hydroxyprogesterone caproate using serial fetal fibronectin and cervical length.
AB  - OBJECTIVE: The objective of the study was to estimate the predictive value of
      cervical length (CL) and fetal fibronectin (fFN) in patients being treated with
      17-alpha-hydroxyprogesterone caproate (17P). METHODS: This was a retrospective
      cohort of 176 patients with a prior spontaneous preterm birth being treated with
      weekly injections of 17P who underwent serial CL and fFN screening. RESULTS: A
      short CL (<=25 mm) was significantly associated with an earlier gestational age
      at delivery and with recurrent preterm birth at less than 37, less than 35, less
      than 34, and less than 32 weeks. A positive fFN was not significantly associated
      with recurrent preterm birth. As a screening test for recurrent preterm birth,
      the positive and negative likelihood ratios for CL were 2.04 and 0.35,
      respectively, whereas for fFN they were 1.22 and 0.98, respectively, indicating
      that fFN did not offer any additional predictive value. CONCLUSION: In patients
      being treated with 17P, cervical length at 22-32 weeks is predictive of recurrent
      preterm birth, but fetal fibronectin is not.

PMID- 22595380
TI  - Prostaglandin receptor EP4 in abdominal aortic aneurysms.
AB  - Abdominal aortic aneurysm (AAA) pathogenesis is distinguished by vessel wall
      inflammation. Cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase-1,
      key components of the most well-characterized inflammatory prostaglandin pathway,
      contribute to AAA development in the 28-day angiotensin II infusion model in
      mice. In this study, we used this model to examine the role of the prostaglandin
      E receptor subtype 4 (EP4) and genetic knockdown of COX-2 expression (70% to 90%)
      in AAA pathogenesis. The administration of the prostaglandin receptor EP4
      antagonist AE3-208 (10 mg/kg per day) to apolipoprotein E (apoE)-deficient mice
      led to active drug plasma concentrations and reduced AAA incidence and severity
      compared with control apoE-deficient mice (P < 0.01), whereas COX-2 genetic
      knockdown/apoE-deficient mice displayed only a minor, nonsignificant decrease in
      incidence of AAA. EP4 receptor protein was present in human and mouse AAA, as
      observed by using Western blot analysis. Aortas from AE3-208-treated mice
      displayed evidence of a reduced inflammatory phenotype compared with controls.
      Atherosclerotic lesion size at the aortic root was similar between all groups. In
      conclusion, the prostaglandin E(2)-EP4 signaling pathway plays a role in the AAA
      inflammatory process. Blocking the EP4 receptor pharmacologically reduces both
      the incidence and severity of AAA in the angiotensin II mouse model, potentially
      via attenuation of cytokine/chemokine synthesis and the reduction of matrix
      metalloproteinase activities.

PMID- 22595381
TI  - [Dual energy CT angiography of the carotid arteries: quality, bone subtraction,
      and radiation dosage using tube voltage 80/140 kV versus 100/140 kV].
AB  - OBJECTIVE: To study the differences in vascular image quality, bone subtraction,
      and dose of radiation of dual energy CT angiography of the supraaortic trunks
      using different tube voltages. MATERIAL AND METHODS: We reviewed the CT
      angiograms of the supraaortic trunks in 46 patients acquired with a 128-slice
      dual source CT scanner using two voltage protocols (80/140 kV and 100/140 kV).
      The "head bone removal" tool was used for postprocessing. We divided the arteries
      into 15 segments. In each segment, we evaluated the image quality of the vessels
      and the effectiveness of bone removal in multiplanar reconstructions (MPR) and in
      maximum intensity projections (MIP) with each protocol, analyzing the trabecular
      and cortical bones separately. We also evaluated the dose of radiation received.
      RESULTS: Of the 46 patients, 13 were studied using 80/140 kV and 33 with 100/140
      kV. There were no significant differences between the two groups in age or sex.
      Image quality in four segments was better in the group examined with 100/140 kV.
      Cortical bone removal in MPR and MIP and trabecular bone removal in MIP were also
      better in the group examined with 100/140 kV. The dose of radiation received was
      significantly higher in the group examined with 100/140 kV (1.16 mSv with 80/140
      kV vs. 1.59 mSv with 100/140 kV). CONCLUSION: Using 100/140 kV increases the dose
      of radiation but improves the quality of the study of arterial segments and bone
      subtraction.

PMID- 22595382
TI  - [Chondrosarcomatous metaplastic carcinoma of the breast, a rare tumor].
AB  - Metaplastic carcinomas of the breast are uncommon, accounting for less than 0.2%
      of all breast cancers. Clinically and radiologically, metaplastic carcinomas are
      indistinguishable from typical ductal carcinomas, and the diagnosis is made
      histologically by the finding of a mesenchymal component. We present a case of
      chondrosarcomatous metaplastic breast carcinoma whose definitive diagnosis
      required immunohistochemical techniques to confirm the malignant epithelial
      component of the tumor. Accurate diagnosis is important because this tumor
      behaves differently: it usually spreads through the blood (whereas typical
      epithelial carcinomas spread through the lymph vessels), metastases present
      during follow-up rather than before diagnosis, and the five-year survival rate is
      35%. 

PMID- 22595383
TI  - Mycophenolate sodium dosing in combination with tacrolimus: pharmacokinetic
      evaluation of a novel regimen in de novo tacrolimus-treated kidney transplant
      patients.
AB  - BACKGROUND: There are no clear guidelines concerning the appropriate dose of
      mycophenolate acid (MPA) to be used in association with tacrolimus. When MPA is
      given at an approved fixed dose in cyclosporine-treated patients, initial
      systemic under exposure is frequent and associated with the occurrence of acute
      rejection. We pharmacologically evaluated in tacrolimus-treated recipients a
      novel dosing regimen of MPA with an initial high dose followed by a gradual
      decrease over time. METHODS: 15 de novo tacrolimus-treated kidney transplant
      patients were administered mycophenolate sodium at the dose of 720 mg b.i.d. for
      the first week post-transplant, 540 mg b.i.d. until Day 30, and then 360 mg
      b.i.d. until Day 90. MPA exposure was evaluated by the 12 h area under MPA
      concentration versus time curve (AUC) determined at Days 2, 7, 15, 30 and 90 post
      transplant. RESULTS: Median MPA AUC was constantly within the therapeutic window
      of 30 - 60 mg/l * h throughout the three months of evaluation. More than 75% of
      patients had a MPA AUC above 30 mg/l * h at Day 2 and Day 7 post-transplant.
      CONCLUSION: This exploratory study suggests that such a dosing regimen of
      mycophenolate sodium might quickly offer and sustain an optimal exposure to MPA
      in tacrolimus-treated kidney transplant patients.

PMID- 22595384
TI  - Effect of perioperative blood transfusions on long term graft outcomes in renal
      transplant patients.
AB  - BACKGROUND: It is established that blood transfusions will promote sensitization
      to human leucocyte antigen (HLA) antigens, increase time spent waiting for
      transplantation and may lead to higher rates of rejection. Less is known about
      how perioperative blood transfusion influence patient and graft outcome. This
      study aims to establish if there is an association between perioperative blood
      transfusion and graft or patient survival. MATERIALS AND METHODS: This was a
      single center, national, retrospective cohort study. Data was collected on
      patients who received kidney transplants over a 14-year period (n = 2,013). The
      primary outcomes were graft survival and mortality in patients who received blood
      transfusions in the perioperative period compared to those who did not. RESULTS:
      Patients who received blood transfusions had lower hemoglobin levels, were more
      likely to be male, and had higher rates of delayed graft function compared to
      those who did not receive a transfusion. The one year graft survival of those
      transfused was 83% compared to 94% in those not transfused (p = < 0.0001).
      Adjustment for confounding showed that the receipt of a blood transfusion
      remained associated with increased graft loss. Hemoglobin levels prior to
      transfusion did not have an influence on graft outcome. CONCLUSION: Perioperative
      blood transfusion is associated with reduced long-term graft survival.

PMID- 22595385
TI  - Fluid balance as an early indicator of acute kidney injury in CV surgery.
AB  - BACKGROUND: We hypothesized that positive fluid balance (FB) is the result of
      intraoperative kidney injury and associated renal vasoconstriction, and therefore
      may be an early clinical indicator of acute kidney injury (AKI). Since rapid
      changes in fluid volume occur during cardiovascular (CV) surgery, we investigated
      the influence of immediate postoperative FB on AKI. MATERIALS AND METHODS: Data
      from the Nesiritide Study were retrospectively analyzed to investigate the
      association between FB and AKI. RESULTS: Patients were classified into a negative
      FB (NegFB, median -1,221 ml, IQR -1,974 to -653 ml, n = 71) and a PosFB (median
      849 ml, IQR 328 - 1,552 ml, n = 19) group based on FB status in the first 24 h
      postoperatively. The PosFB group had a higher incidence of AKI (NegFB 25.3% vs.
      PosFB 47.3%, p = 0.090) compared to the NegFB group. The difference in the
      incidence of AKI was significantly higher (NegFB 25.3% vs. high- PosFB 80%, p =
      0.001) in the subset of patients who had FB >= 849 ml (highPosFB, n = 10). The
      highPosFB group demonstrated a significantly elevated risk for AKI in both
      unadjusted (OR = 9.8, 95% CI 1.9 - 51.2, p = 0.007) and multivariate models (OR =
      8.1, 95% CI 1.5 - 45.1, p = 0.03). CONCLUSIONS: PosFB in the immediate
      postoperative period may be an independent early indicator of AKI in patients
      undergoing CV surgery.

PMID- 22595386
TI  - The effect of omega-3 fatty acids on the atherogenic lipoprotein phenotype in
      patients with nephrotic range proteinuria.
AB  - AIMS: Patients with nephrotic range proteinuria are known to have an increased
      risk of cardiovascular disease partly due to possessing the atherogenic
      lipoprotein phenotype. The aim of this study was to examine the effect of high
      dose omega-3 fatty acids on atherogenic triglyceride rich lipoproteins in
      patients with nephrotic range proteinuria, comparing their effect on lipoprotein
      profiles in age and sex matched controls. METHODS: 17 patients with nephrotic
      range proteinuria and 17 age and sex matched controls were studied. Fasting
      lipids and lipoproteins were measured before and after 8 weeks treatment with 4 g
      daily of omega-3 fatty acids (Omacor(r)). RESULTS: In patients with proteinuria
      treatment reduced plasma triglyceride by a mean of 0.45 mmol/l (95%CI 0.16 -
      0.74, p = 0.005) and plasma very low density lipoprotein cholesterol by a mean of
      0.38 (95%CI 0.01 - 0.75, p = 0.04). LDL III concentration fell from 178.8 mg/dl
      (61.6 - 231.0) to 96.1 mg/dl (49.3 - 204.5), p = 0.05. In patients treatment
      altered the LDL profile so that LDLIII which was the major subfraction present at
      baseline was reduced from 49.9% to 29.8% (p = 0.01). Remnant lipoproteins (RLP)
      also fell with a mean reduction of 3.5 mg/dl in RLP-Cholesterol (95%CI 0.1 - 6.9,
      p = 0.05) and 12.4 mg/dl in RLP-triglyceride (95%CI 2.6 - 22.2, p = 0.03). There
      was however a 0.6 mmol/l rise in LDL-C (p = 0.06) in the patients. Treatment did
      not alter HDL-C. CONCLUSION: In patients with nephrotic range proteinuria, omega
      3 fatty acids reduced triglyceride rich lipoproteins, LDL III and remnant
      lipoproteins. A tendency to an increase in LDL-C was observed but this was offset
      by an alteration in the distribution of the LDL profile towards lighter, larger
      LDL particles. We propose that treatment with omega-3 fatty acids in conjunction
      with a statin may be the ideal therapy in these patients.

PMID- 22595387
TI  - ANCA-associated crescentic glomerulonephritis with immune complex deposits.
AB  - BACKGROUND: Several authors have reported cases of anti-neutrophil cytoplasmic
      antibody (ANCA)-associated crescentic glomerulonephritis (CGN) with definite
      immune complex (IC) deposits, however, the clinical and pathological significance
      of IC deposits in patients with ANCA-associated CGN remains unclear. METHODS:
      Renal biopsy specimens from 28 patients with a diagnosis of CGN and positivity
      for anti-myeloperoxidase (MPO)-ANCA were retrospectively evaluated. Clinical data
      were compared between patients with IC deposits (Group A) and patients without IC
      deposits (Group B). RESULTS: In 12 patients (43%; Group A), IC deposits were
      detected in the mesangium and/or along the glomerular capillary walls, while
      typical pauci-immune CGN without IC deposits was found in 16 patients (57%; Group
      B). Compared with Group B, Group A had lower levels of MPO-ANCA (171 +/- 156 vs.
      352 +/- 299 EU) and C-reactive protein (CRP) (0.63 +/- 1.04 vs. 4.45 +/- 4.00
      mg/dl), as well as less pulmonary involvement (8.3% vs. 56.3%) at diagnosis.
      However, Group A had significantly heavier proteinuria (2.46 +/- 1.67 vs. 0.76 +/
      0.52 g/d). Group A was classified into three subgroups: Group A1 with mesangial
      IgA and C3 deposits, A2 with mesangial IgG and C3 deposits, and A3 with IgG and
      C3 deposits mainly in the capillary walls. CONCLUSIONS: ANCA-associated CGN
      causes two types of renal involvement, which are the pauci-immune type without IC
      deposits and the IC deposition type that involves three patterns of IC deposition
      in the glomeruli. The reason why IC deposits are associated with renal-limited
      vasculitis and not systemic vasculitis remains unclear.

PMID- 22595388
TI  - Renal biopsy in patients aged 80 years and older: a single-center experience in
      Japan.
AB  - BACKGROUND: There is a paucity of data on renal biopsy in a large number of the
      very elderly (age >= 80 years) worldwide. METHODS: Clinicopathological features
      in 73 patients aged >= 80 years were evaluated and compared with control groups
      of 172 patients aged 60 - 61 years and 128 patients aged 70 - 71 years. RESULTS:
      The common indications for biopsy in the very elderly were nephrotic syndrome
      (NS), followed by proteinuria without NS and/or hematuria, and acute kidney
      injury (AKI). Histological diagnoses were considered to potentially modify
      treatment in 57 cases (78.1%): the most frequent diagnosis was membranous
      nephropathy, followed by minimal change disease, and various other diseases.
      There were no biopsy procedure-related serious complications. Clinical assessment
      of treatments was evaluated in 38 of 54 patients with AKI and/or NS. Improvement
      in renal dysfunction or NS was observed in 24 of 30 (80%) patients who received
      immunosuppressive therapy. There were statistically significant differences in
      the disease spectrum between the very elderly and control groups. CONCLUSIONS:
      This is the first report of renal biopsy findings in a relatively large number of
      Japanese very elderly patients. Histological observations are useful aids in
      estimating the prognosis and therapy selection for renal disorders, even in the
      very elderly.

PMID- 22595389
TI  - The prevalence of peripheral neuropathy in hemodialysis patients.
AB  - BACKGROUND/AIMS: Uremic Neuropathy (UN) highly limits the individual self
      sufficiency causing near-continuous pain. An estimation of the actual UN
      prevalence among hemodialysis patients was the aim of the present work. METHODS:
      We studied 225 prevalent dialysis patients from two Italian Centers. The Michigan
      Neuropathy Score Instrument (MNSI), already validated in diabetic neuropathy, was
      used for the diagnosis of UN. It consisted of a questionnaire (MNSI_Q) and a
      physical-clinical evaluation (MNSI_P). Patients without any disease possibly
      inducing secondary neuropathy and with MNSI score >= 3 have been diagnosed as
      affected by UN. Electroneurographic (ENG) lower limbs examination was performed
      in these patients to compare sensory conduction velocities (SCV) and sensory
      nerve action potentials (SNAP) with the MNSI results. RESULTS: 37 patients
      (16.4%) were identified as being affected by UN, while 9 (4%) presented a score <
      3 in spite of neuropathic symptoms. In the 37 UN patients a significant
      correlation was found between MNSI_P and SCV (r2 = 0.1959; p < 0.034) as well as
      SNAP (r2 = 0.3454; p = 0.027) both measured by ENG. CONCLUSIONS: UN is an
      underestimated disease among the dialysis population even though it represents a
      huge problem in terms of pain and quality of life. MNSI could represent a valid
      and simple clinical-instrumental screening test for the early diagnosis of UN in
      view of an early therapeutic approach.

PMID- 22595391
TI  - Fractional excretion and reabsorption in chronic kidney disease.
AB  - The concepts of fractional excretion and reabsorption are often employed to
      elucidate the contribution of tubular transport to plasma concentrations.
      Fractional excretion of substance x, FEx, is the ratio of the urinary excretion
      rate to the filtration rate of x, or Ex/Fx. Fractional tubular reabsorption of x,
      FTRx, is the ratio of the reabsorption rate to the filtration rate of x, or
      TRx/Fx. When plasma is in equilibrium with respect to x, net influx (Ix) from gut
      and tissue determines Ex, and [x]p = Ex/GFR + TRx/GFR. In chronic kidney disease
      (CKD), Ex/GFR rises as GFR falls if Ix does not fall commensurately; at the same
      time, TRx/GFR may fall, remain unchanged, or rise. If TRx/GFR rises, a
      simultaneous, proportionately greater increment in Ex/GFR causes FEx to rise also
      and FTRx to fall secondarily. In this circumstance, FTRx is lower than normal
      even though reabsorption of x is increased per volume of filtrate. This paper
      reviews pertinent homeostatic principles, illustrates the potential for
      divergence of TRx/GFR and FTRx as GFR falls, and summarizes the conditions
      required for the divergence. Clinical examples show reduced FTRx despite
      increased TRx/GFR for phosphorus and urate, and analyses suggest that such
      discrepancies are often inevitable. Methods are described and arguments are
      advanced for using TRx/GFR to quantify tubular function in CKD.

PMID- 22595390
TI  - Dietary intervention focused on phosphate intake in hemodialysis patients with
      hyperphosphoremia.
AB  - BACKGROUND: Elevated serum phosphorus has been identified as a cardiovascular
      risk factor. This study aimed to assess the effectiveness of dietary intervention
      to reduce phosphorus intake and to improve the calcium-phosphorus metabolism in
      hemodialysis patients. DESIGN: Patients were included in a 6-month, 2-group
      experimental study if their previous 3-month average serum phosphorus was over
      5.5 mg/dl. Patients were allocated to intensive dietary intervention or usual
      dietary recommendations. The clinical end-points were the multivariate-adjusted
      change in serum phosphorus and the number of patients who achieved serum
      phosphorus levels of < 5.5 mg/dl and serum phosphorus levels of < 5 mg/dl.
      RESULTS: 80 dialysis patients completed the study, 41 in the experimental group
      and 39 in the control group. After 6 months, phosphorus intake (702 +/- 168 vs.
      872 +/- 242 mg/24 h; p = 0.002) was lower in the experimental group than in the
      control group, with no inter-group differences in protein-caloric intake. Serum
      phosphorus decreased 1.67 mg/dl in the experimental group and 0.58 mg/dl in the
      control group (multivariate-adjusted difference 0.93 mg/ dl; 95% CI 0.34 - 1.52;
      p = 0.003). Serum phosphorus < 5.5 mg/dl and serum phosphorus < 5 mg/dl were
      attained more frequently in the experimental group (51 vs. 18%, p = 0.002 and
      31.7 vs. 15.4%, p = 0.08 respectively). CONCLUSIONS: Intensive dietary
      intervention focusing on phosphorus intake may be useful to reduce phosphorus
      retention and to improve calcium-phosphorus metabolism in hemodialysis patients.

PMID- 22595392
TI  - Licorice-related rhabdomyolysis: a big price for a sweet tooth.
AB  - A 50-year-old lady on hydrochlorothiazide (HCTZ) presented to the hospital after
      4 days of generalized muscle aches and dark urine. She admitted to consuming one
      and a half bags of black licorice bites containing 2% natural licorice during the
      past 3 weeks. Examination showed high blood pressure, while labs revealed
      elevated creatine kinase, hypokalemia, hypocalcemia and hypophosphatemia with low
      aldosterone and plasma renin levels and high intact PTH. The active component of
      licorice is glycyrrhizic acid, which inhibits an enzyme required to convert
      cortisol to a less active metabolite, cortisone. This causes excess cortisol,
      simulating syndrome of apparent mineralocorticoid excess (AME), thus resulting in
      hypertension, hypokalemia and metabolic alkalosis. In our patient, licorice
      induced hypokalemia resulted in rhabdomyolysis. The rhabdomyolysis along with the
      effect of licorice led to secondary hypocalcaemia, which in turn triggered
      secondary hyperparathyroidism. This might have had a phosphaturic effect that
      caused hypophosphatemia, further worsening rhabdomyolysis. CONCLUSION: This case
      illustrates the complex relationship of various electrolytes, which can lead to
      self perpetuation of the disease, hence demanding more vigilance.

PMID- 22595393
TI  - Membranous nephropathy induced by pegylated interferon alpha-2a therapy for
      chronic viral hepatitis B.
AB  - Interferon is used to treat chronic viral hepatitis because of low drug
      resistance and a high remission rate. However, its propensity to induce and
      modify autoimmunity has been reported. We used pegylated interferon alpha-2a to
      treat a patient with chronic viral hepatitis B. After 5 months of this therapy,
      the patient developed membranous nephropathy. Complete remission of his nephrotic
      syndrome was achieved after 1 year of cyclosporine and corticosteroid therapy.
      During this same period, his chronic viral hepatitis B was controlled by
      entecavir. To our knowledge, this is the first case in which membranous
      nephropathy developed during pegylated interferon alpha-2a therapy for chronic
      hepatitis B. The autoimmune modulation induced by interferon is the most likely
      mechanism for this complication.

PMID- 22595394
TI  - Membranous nephropathy with predominance of C1q: another variant of C1q
      nephropathy?
AB  - Originally described as a proliferative glomerulonephritis, C1q nephropathy is
      nowadays mostly recognized as a variant of focal segmental glomerulosclerosis or
      minimal change disease. We describe a 30-year-old male patient with nephrotic
      range proteinuria. Kidney biopsy demonstrated a membranous nephropathy with
      predominant staining for C1q. Under conservative therapy the outcome was
      favorable. We suggest that this case represents another variant of C1q
      nephropathy, thus broadening the spectrum of the disease.

PMID- 22595395
TI  - A case report of minimal change nephrotic syndrome complicated with portal,
      splenic and superior mesenteric vein thrombosis.
AB  - BACKGROUND: Venous thrombosis is common in nephrotic syndrome, but portal vein
      thrombosis has a relatively low incidence in patients with nephrotic syndrome. We
      describe here a case of an 18-year old male student with newly diagnosed
      nephrotic syndrome that was complicated with portal, splenic and superior
      mesenteric vein thrombosis. CONCLUSION: In the presence of newly diagnosed
      nephrotic syndrome of minimal change disease, thrombus formation can occur and
      should be noted, particularly when it occurs, in rare sites. The recognition in
      nephrotic syndrome complicated with portal, splenic and superior mesenteric vein
      thrombosis should be emphasized.

PMID- 22595396
TI  - The uncertainty of rituximab and steroid dosing in refractory steroid-resistant
      nephrotic syndrome.

PMID- 22595397
TI  - Contribution of autonomic dysfunction to abnormal exercise blood pressure in type
      2 diabetes mellitus.
AB  - OBJECTIVES: The purpose of this study was to compare the presence and severity of
      autonomic dysfunction in type 2 diabetes mellitus patients, with and without
      exaggerated blood pressure responses to exercise. DESIGN: We performed a cross
      sectional analysis of 98 patients with type 2 diabetes mellitus (aged 59+/-9).
      METHODS: Both time (standard deviation of RR intervals, root-mean-square of
      successive RR interval differences) and frequency (total spectral power, high
      frequency, low frequency, very low frequency) domains of heart rate variability
      were analysed in a 5 min recording at rest and 20 min after a maximal treadmill
      test. An exaggerated blood pressure response to exercise was identified by peak
      blood pressure >=190/105 mmHg (women) or >=210/105 mmHg (men). RESULTS: Each
      group of either exaggerated exercise blood pressure response or normal blood
      pressure response consisted of 49 patients. At rest there were no significant
      differences between groups for all time and frequency domain parameters of heart
      rate variability. Post-exercise, there was a significant (p<0.05) reduction in
      the SDNN, RMSSD and TP in the exaggerated exercise blood pressure group.
      Independent correlates (p<0.01) of exercise systolic blood pressure included post
      exercise TP, resting systolic blood pressure, cardiac autonomic neuropathy and
      beta-blockers (beta=-0.28, adj. R2 = 0.32, p<0.001). CONCLUSIONS: Reduced post
      exercise heart rate variability in patients with type 2 diabetes mellitus, with
      an exaggerated exercise blood pressure response suggests preclinical autonomic
      dysfunction characterized by impaired vagal modulation.

PMID- 22595398
TI  - Inter-domain interactions influence the stability and catalytic activity of the
      bi-domain protein tyrosine phosphatase PTP99A.
AB  - The two protein tyrosine phosphatase (PTP) domains in bi-domain PTPs share high
      sequence and structural similarity. However, only one of the two PTP domains is
      catalytically active. Here we describe biochemical studies on the two tandem PTP
      domains of the bi-domain PTP, PTP99A. Phosphatase activity, monitored using small
      molecule as well as peptide substrates, revealed that the inactive (D2) domain
      activates the catalytic (D1) domain. Thermodynamic measurements suggest that the
      inactive D2 domain stabilizes the bi-domain (D1-D2) protein. The mechanism by
      which the D2 domain activates and stabilizes the bi-domain protein is governed by
      few interactions at the inter-domain interface. In particular, mutating Lys990 at
      the interface attenuates inter-domain communication. This residue is located at a
      structurally equivalent location to the so-called allosteric site of the
      canonical single domain PTP, PTP1B. These observations suggest functional
      optimization in bi-domain PTPs whereby the inactive PTP domain modulates the
      catalytic activity of the bi-domain enzyme.

PMID- 22595399
TI  - Primary total knee arthroplasty using the P.F.C Sigma(r)-rotating platform
      cruciate retaining endoprosthesis--a 6 year follow up.
AB  - BACKGROUND: Mobile-bearing Total Knee Replacement allows unconstrained axial
      rotation. Increased articular conformity minimizes polyethylene contact stresses,
      thereby reducing linear wear and fatigue failure. METHODS: We prospectively
      reviewed a consecutive series of 161 patients with mobile bearing total knee
      replacements using the PFC Sigma Cruciate Retaining Rotating Platform System.
      (DePuy, Leeds, United Kingdom) with midterm follow up (minimum 6 and maximum 9
      years, mean 7.2 years). One hundred forty-seven patients from February 2001 to
      March 2004 were followed up till date. Primary osteoarthritis 96%; was the main
      indication followed by rheumatoid arthritis 3% and one case of psoriatic
      arthritis. Fifty-seven percent were females with mean age of 69.5 years (Range 51
      90 years). Oxford and American Knee Society scores were measured. RESULTS: Mean
      Oxford score improved from 43 (Range 29-55) pre operatively to 21(Range 13-44) at
      last follow up and mean Knee Society score from 53 (Range 43-70) to 80 (Range 58
      90). Range of movement improved from 91 degrees  (Range 70-110) to 113 degrees 
      (Range 75-130) at last follow up. One patient had dislocation of bearing needing
      manipulation. One patient had superficial infection treated with antibiotics. No
      patients had deep infection. There was one case reported of deep vein thrombosis
      and one of non-fatal pulmonary embolism. CONCLUSION: The midterm results in our
      series with PFC Sigma mobile bearing knee replacement are excellent with good
      outcome scores. Cohort will be followed for long term results. Level of Evidence
      IV.

PMID- 22595400
TI  - Mediterranean diet polyphenols reduce inflammatory angiogenesis through MMP-9 and
      COX-2 inhibition in human vascular endothelial cells: a potentially protective
      mechanism in atherosclerotic vascular disease and cancer.
AB  - Diets with high content of antioxidant polyphenols are associated with low
      prevalence of cardiovascular diseases and cancer. Inflammatory angiogenesis is a
      key pathogenic process both in cancer and atherosclerosis, and is tightly
      regulated by the proinflammatory enzyme cyclooxygenase (COX)-2 and the matrix
      degrading enzymes matrix metalloproteinases (MMPs). We studied the effects of
      antioxidant polyphenols from virgin olive oil (oleuropein and hydroxytyrosol) and
      red wine (resveratrol and quercetin) on endothelial cell angiogenic response in
      vitro, and explored underlying mechanisms. Cultured endothelial cells were pre
      incubated with 0.1-50 MUmol/L polyphenols before stimulation with phorbol
      myristate acetate (PMA). All tested polyphenols reduced endothelial cell tube
      formation on matrigel and migration in wound healing assays. The reduced
      angiogenesis was associated with the inhibition of PMA-induced COX-2 protein
      expression and prostanoid production, as well as MMP-9 protein release and
      gelatinolytic activity. These effects were accompanied by a significant reduction
      in the stimulated intracellular reactive oxygen species levels and in the
      activation of the redox-sensitive transcription factor nuclear factor (NF)
      kappaB. Our findings reveal that olive oil and red wine polyphenols reduce
      inflammatory angiogenesis in cultured endothelial cells, through MMP-9 and COX-2
      inhibition, supporting a potential protective role for dietary polyphenols in
      atherosclerotic vascular disease and cancer.

PMID- 22595401
TI  - Protein interactions in 3D: from interface evolution to drug discovery.
AB  - Over the past 10years, much research has been dedicated to the understanding of
      protein interactions. Large-scale experiments to elucidate the global structure
      of protein interaction networks have been complemented by detailed studies of
      protein interaction interfaces. Understanding the evolution of interfaces allows
      one to identify convergently evolved interfaces which are evolutionary unrelated
      but share a few key residues and hence have common binding partners.
      Understanding interaction interfaces and their evolution is an important basis
      for pharmaceutical applications in drug discovery. Here, we review the algorithms
      and databases on 3D protein interactions and discuss in detail applications in
      interface evolution, drug discovery, and interface prediction.

PMID- 22595402
TI  - Outbreak of mastitis in sheep caused by multi-drug resistant Enterococcus
      faecalis in Sardinia, Italy.
AB  - An outbreak of infective mastitis due to Enterococcus faecalis occurred in an
      intensive sheep farm in north Sardinia (Italy). E. faecalis, which is only rarely
      isolated from sheep milk, was unexpectedly found in 22.3% of positive samples at
      microbiological examination. Forty-five out of the 48 E. faecalis isolates showed
      the same multi-drug resistance pattern (cloxacillin, streptomycin, kanamycin,
      clindamycin, oxytetracycline). E. faecalis isolates were analysed by pulsed-field
      gel electrophoresis, and all 45 multi-drug resistant strains showed an
      indistinguishable macrorestiction profile, indicating their clonal origin. To our
      knowledge, this is the first report of an outbreak of mastitis in sheep caused by
      E. faecalis.

PMID- 22595403
TI  - The year in cardiac imaging.

PMID- 22595404
TI  - Temporal trends in and factors associated with bleeding complications among
      patients undergoing percutaneous coronary intervention: a report from the
      National Cardiovascular Data CathPCI Registry.
AB  - OBJECTIVES: The purpose of this study was to examine temporal trends in post
      percutaneous coronary intervention (PCI) bleeding among patients with elective
      PCI, unstable angina (UA)/non-ST-segment elevation myocardial infarction
      (NSTEMI), and ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The
      impact of bleeding avoidance strategies on post-PCI bleeding rates over time is
      unknown. METHODS: Using the CathPCI Registry, we examined temporal trends in post
      PCI bleeding from 2005 to 2009 among patients with elective PCI (n = 599,524),
      UA/NSTEMI (n = 836,103), and STEMI (n = 267,632). We quantified the linear time
      trend in bleeding using 3 sequential logistic regression models: 1) clinical
      factors; 2) clinical + vascular access strategies (femoral vs. radial, use of
      closure devices); and 3) clinical, vascular strategies + antithrombotic
      treatments (anticoagulant +/- glycoprotein IIb/IIIa inhibitor [GPI]). Changes in
      the odds ratio for time trend in bleeding were compared using bootstrapping and
      converted to risk ratio. RESULTS: An approximate 20% reduction in post-PCI
      bleeding was seen (elective PCI: 1.4% to 1.1%; UA/NSTEMI: 2.3% to 1.8; STEMI:
      4.9% to 4.5%). Radial approach remained low (<3%), and closure device use
      increased marginally from 44% to 49%. Bivalirudin use increased (17% to 30%),
      whereas any heparin + GPI decreased (41% to 28%). There was a significant 6% to
      8% per year reduction in annual bleeding risk in UA/NSTEMI and elective PCI, but
      not in STEMI. Antithrombotic strategies were associated with roughly half of the
      reduction in annual bleeding risk: change in risk ratio from 7.5% to 4% for
      elective PCI, and 5.7% to 2.8% for UA/NSTEMI (both p <0.001). CONCLUSIONS: The
      nearly 20% reduction in post-PCI bleeding over time was largely due to temporal
      changes in antithrombotic strategies. Further reductions in bleeding
      complications may be possible as bleeding avoidance strategies evolve, especially
      in STEMI.

PMID- 22595405
TI  - Appropriateness of coronary revascularization for patients without acute coronary
      syndromes.
AB  - OBJECTIVES: The purpose of this study was to determine appropriateness of
      percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG)
      surgery performed in New York for patients without acute coronary syndrome (ACS)
      or previous CABG surgery. BACKGROUND: The American College of Cardiology
      Foundation (ACCF) and 6 other societies recently published joint appropriateness
      criteria for coronary revascularization. METHODS: Data from patients who
      underwent CABG surgery and PCI without acute coronary syndrome or previous CABG
      surgery in New York in 2009 and 2010 were used to assess appropriateness and to
      examine the variation across hospitals in inappropriateness ratings. RESULTS: Of
      the 8,168 patients undergoing CABG surgery in New York without ACS/prior CABG who
      could be rated, 90.0% were appropriate for revascularization, 1.1% were
      inappropriate, and 8.6% were uncertain. Of the 33,970 PCI patients eligible for
      rating, 28% lacked sufficient information to be rated. Of the patients who could
      be rated, 36.1% were appropriate, 14.3% were inappropriate, and 49.6% were
      uncertain. A total of 91% of the patients undergoing PCI who were classified as
      inappropriate had 1- or 2-vessel disease without proximal left anterior
      descending artery disease and had no or minimal anti-ischemic medical therapy.
      CONCLUSIONS: For patients without ACS/prior CABG, only 1% of patients undergoing
      CABG surgery who could be rated were found to be inappropriate for the procedure
      according to the ACCF appropriateness criteria, but 14% of the PCI patients who
      could be rated were found to be inappropriate, and 28% lacked enough noninvasive
      test information to be rated.

PMID- 22595406
TI  - The need to improve the appropriate use of coronary revascularization: challenges
      and opportunities.

PMID- 22595407
TI  - Impact of coronary plaque composition on cardiac troponin elevation after
      percutaneous coronary intervention in stable angina pectoris: a computed
      tomography analysis.
AB  - OBJECTIVES: The authors used multidetector computed tomography (MDCT) to study
      the relation between culprit plaque characteristics and cardiac troponin T (cTnT)
      elevation after percutaneous coronary intervention (PCI). BACKGROUND:
      Percutaneous coronary intervention is often complicated by post-procedural
      myocardial necrosis manifested by elevated cardiac biomarkers. METHODS: Stable
      angina patients (n = 107) with normal pre-PCI cTnT levels underwent 64-slice MDCT
      before PCI to evaluate plaque characteristics of culprit lesions. Patients were
      divided into 2 groups according to presence (group I, n = 36) or absence (group
      II, n = 71) of post-PCI cTnT elevation >=3 times the upper limit of normal (0.010
      ng/ml) at 24 h after PCI. RESULTS: Computed tomography attenuation values were
      significantly lower in group I than in group II (43.0 [26.5 to 75.7] HU vs. 94.0
      [65.0 to 109.0] HU, p < 0.001). Remodeling index was significantly greater in
      group I than in group II (1.20 +/- 0.18 vs. 1.04 +/- 0.15, p < 0.001). Spotty
      calcification was observed significantly more frequently in group I than in group
      II (50% vs. 11%, p < 0.001). Multivariate analysis showed presence of positive
      remodeling (remodeling index >1.05; odds ratio: 4.54; 95% confidence interval:
      1.36 to 15.9; p = 0.014) and spotty calcification (odds ratio: 4.27; 95%
      confidence interval: 1.30 to 14.8; p = 0.016) were statistically significant
      independent predictors for cTnT elevation. For prediction of cTnT elevation, the
      presence of all 3 variables (CT attenuation value <55 HU; remodeling index >1.05,
      and spotty calcification) showed a high positive predictive value of 94%, and
      their absence showed a high negative predictive value of 90%. CONCLUSIONS: MDCT
      may be useful in detecting which lesions are at high risk for myocardial necrosis
      after PCI.

PMID- 22595408
TI  - Predicting periprocedural myocardial infarction: target-lesion plaque
      characterization with coronary computed tomography angiography.

PMID- 22595409
TI  - Sudden cardiac death in patients with human immunodeficiency virus infection.
AB  - OBJECTIVES: The aim of this study was to determine the incidence and clinical
      characteristics of sudden cardiac death (SCD) in patients with human
      immunodeficiency virus (HIV) infection. BACKGROUND: As the HIV-infected
      population ages, cardiovascular disease prevalence and mortality are increasing,
      but the incidence and features of SCD have not yet been described. METHODS: The
      records of 2,860 consecutive patients in a public HIV clinic in San Francisco
      between April 2000 and August 2009 were examined. Identification of deaths,
      causes of death, and clinical characteristics were obtained by search of the
      National Death Index and/or clinic records. SCDs were determined using published
      retrospective criteria: 1) the International Classification of Diseases-10th
      Revision, code for all cardiac causes of death; and (2) circumstances of death
      meeting World Health Organization criteria. RESULTS: Of 230 deaths over a median
      of 3.7 years of follow-up, 30 (13%) met SCD criteria, 131 (57%) were due to
      acquired immune deficiency syndrome (AIDS), 25 (11%) were due to other (natural)
      diseases, and 44 (19%) were due to overdoses, suicides, or unknown causes. SCDs
      accounted for 86% of all cardiac deaths (30 of 35). The mean SCD rate was 2.6 per
      1,000 person-years (95% confidence interval: 1.8 to 3.8), 4.5-fold higher than
      expected. SCDs occurred in older patients than did AIDS deaths (mean 49.0 vs.
      44.9 years, p = 0.02). Compared with AIDS and natural deaths combined, SCDs had a
      higher prevalence of prior myocardial infarction (17% vs. 1%, p < 0.0005),
      cardiomyopathy (23% vs. 3%, p < 0.0005), heart failure (30% vs. 9%, p = 0.004),
      and arrhythmias (20% vs. 3%, p = 0.003). CONCLUSIONS: SCDs account for most
      cardiac and many non-AIDS natural deaths in HIV-infected patients. Further
      investigation is needed to ascertain underlying mechanisms, which may include
      inflammation, antiretroviral therapy interruption, and concomitant medications.

PMID- 22595410
TI  - Head-to-head comparison of left ventricular function assessment with 64-row
      computed tomography, biplane left cineventriculography, and both 2- and 3
      dimensional transthoracic echocardiography: comparison with magnetic resonance
      imaging as the reference standard.
AB  - OBJECTIVES: This study was designed to compare the accuracy of 64-row contrast
      computed tomography (CT), invasive cineventriculography (CVG), 2-dimensional
      echocardiography (2D Echo), and 3-dimensional echocardiography (3D Echo) for left
      ventricular (LV) function assessment with magnetic resonance imaging (MRI).
      BACKGROUND: Cardiac function is an important determinant of therapy and is a
      major predictor for long-term survival in patients with coronary artery disease.
      A number of methods are available for assessment of function, but there are
      limited data on the comparison between these multiple methods in the same
      patients. METHODS: A total of 36 patients prospectively underwent 64-row CT, CVG,
      2D Echo, 3D Echo, and MRI (as the reference standard). Global and regional LV
      wall motion and ejection fraction (EF) were measured. In addition, assessment of
      interobserver agreement was performed. RESULTS: For the global EF, Bland-Altman
      analysis showed significantly higher agreement between CT and MRI (p < 0.005, 95%
      confidence interval: +/-14.2%) than for CVG (+/-20.2%) and 3D Echo (+/-21.2%).
      Only CVG (59.5 +/- 13.9%, p = 0.03) significantly overestimated EF in comparison
      with MRI (55.6 +/- 16.0%). CT showed significantly better agreement for stroke
      volume than 2D Echo, 3D Echo, and CVG. In comparison with MRI, CVG-but not CT
      significantly overestimated the end-diastolic volume (p < 0.001), whereas 2D Echo
      and 3D Echo significantly underestimated the EDV (p < 0.05). There was no
      significant difference in diagnostic accuracy (range: 76% to 88%) for regional LV
      function assessment between the 4 methods when compared with MRI. Interobserver
      agreement for EF showed high intraclass correlation for 64-row CT, MRI, 2D Echo,
      and 3D Echo (intraclass correlation coefficient >0.8), whereas agreement was
      lower for CVG (intraclass correlation coefficient = 0.58). CONCLUSIONS: 64-row CT
      may be more accurate than CVG, 2D Echo, and 3D Echo in comparison with MRI as the
      reference standard for assessment of global LV function.

PMID- 22595411
TI  - The exposure-dependent effects of aged secondhand smoke on endothelial function.
AB  - OBJECTIVES: The aim of this study was to investigate whether exposure to a range
      of relatively low concentrations of aged secondhand smoke (SHS), similar to those
      encountered commonly in the community, would impair endothelial function in a
      concentration-dependent manner. BACKGROUND: Exposure to SHS impairs endothelial
      function in humans. The concentration-dependent relationship for aged SHS effects
      on endothelial function after an exposure of short duration is unknown. METHODS:
      Thirty-three healthy nonsmokers were exposed to 1 of 2 low levels of aged SHS or
      to conditioned filtered air for 30 min. The primary end point was change in
      maximal percent brachial artery flow-mediated dilation after exposure. RESULTS:
      In a linear regression model for each increase in SHS exposure by 100 MUg/m(3)
      respirable suspended particles, the absolute maximal percent brachial artery flow
      mediated dilation was reduced by 0.67%. We did not find evidence of a threshold
      for the effect of SHS on flow-mediated dilation. CONCLUSIONS: Short-term exposure
      to real-world levels of aged SHS for 30 min resulted in a concentration-dependent
      decrease in endothelial function as measured by flow-mediated dilation.

PMID- 22595412
TI  - Perfect correspondence of mitral valve perforation using real-time 3-dimensional
      transesophageal echocardiography.

PMID- 22595413
TI  - Instantaneous wave-free ratio and fractional flow reserve: close, but not close
      enough!

PMID- 22595414
TI  - A new adenosine-independent index of stenosis severity: why would one assess a
      coronary stenosis differently?

PMID- 22595415
TI  - Instantaneous wave-free ratio or fractional flow reserve without hyperemia:
      novelty or nonsense?

PMID- 22595417
TI  - Quadruple valve replacement: visualization with 256-slice computed tomography.

PMID- 22595418
TI  - Examination of the trait facets of the five-factor model in discriminating
      specific mood and anxiety disorders.
AB  - Structural models of the mood and anxiety disorders postulate that each disorder
      has a shared component that can account for comorbidity and its own unique
      component that distinguishes it from others. The principal aim of the current
      study was to determine the extent to which the 30 facets of the Five-Factor Model
      (FFM), as measured by the Revised NEO Personality Inventory (NEO PI-R),
      contribute to the identification of the unique component in mood and anxiety
      disorders in treatment-seeking clinical samples. Participants (N=610) were
      psychiatric outpatients with principal DSM-IV diagnoses (Diagnostic and
      Statistical Manual-IV; American Psychiatric Association, 1994) diagnoses of major
      depressive disorder (MDD), post-traumatic stress disorder (PTSD), generalized
      social phobia (GSP), panic disorder with/without agoraphobia (PD; PD/A) or
      obsessive-compulsive disorder (OCD). Results suggest that approximately half of
      the variance in differences between these diagnoses is associated with specific
      characteristics represented by the FFM facets. Unique personality profiles for
      the MDD, GSP, PTSD and, to a lesser extent, OCD groups emerged. Broad traits of
      the FFM, when broken into more narrow components at the facet level, contribute
      significantly to the identification of unique aspects associated with specific
      mood and anxiety disorders. The integration of lower and higher levels of
      structural examination of the mood and anxiety disorders is discussed.

PMID- 22595419
TI  - [Self-disclosure of a HIV-positive serostatus: factors favoring disclosure and
      consequences for persons living with HIV/AIDS in Burkina Faso].
AB  - Disclosure of HIV-serostatus remains a way to avoid sexual transmission of HIV
      because it allows partners to take the necessary protective measures, e.g. use of
      condoms. Disclosure is nevertheless difficult due to the discrimination
      associated with HIV. The objective of this study was to analyze factors leading
      to self-disclosure of HIV-positive status within a sample of persons of both
      sexes attending different healthcare services in Burkina Faso. METHODOLOGY: Cross
      sectional study conducted by interviewing 740 patients in 26 healthcare services.
      Univariate (Chi(2) test) and multivariate (logistic regression) analyses were
      performed. The significance level was 5%. Qualitative data on factors associated
      with self-disclosure of HIV-positive status were analyzed. RESULTS: The majority
      of the patients (81.4%) informed at least one person who was very often a close
      relative (descendant, ascendant and sibling) or the partner. At multivariate
      analysis, HIV-serostatus was associated with using antiretroviral treatment,
      (OR=0.40, 95% CI: 0.3-0.7, P<0.001), known HIV-serostatus for at least one year
      (OR=0.6; 95% CI: 0.4-0.9), living in couple (2.3; 95% CI: 1.4-3.8). CONCLUSION:
      In a context limiting HIV testing due to the fear of social stigma, these results
      appear to be in favor of the Voluntary Counseling Testing model with a focus on
      the couple and/or families.

PMID- 22595420
TI  - [Needs and expectations of Alzheimer's disease family caregivers].
AB  - BACKGROUND: Family members of people suffering from Alzheimer's disease play a
      major role in providing daily life care for their relatives. Compared to non
      caregivers, they present increased risks of mortality as well as psychological
      and physical co-morbidity. Altered relationships between caregivers and medical
      staff and dissatisfaction with the quality of help provided tend to increase the
      risk of depression and anxiety disorders among caregivers. The present study
      aimed at exploring the needs and expectations of family caregivers of patients
      with Alzheimer's disease who request medical assistance for their relatives.
      METHODS: The present analysis is an ancillary study of a large multicentric
      controlled randomized study designed to assess the efficacy of three non
      pharmacological treatments in Alzheimer's disease, in which 645 mild-to-moderate
      Alzheimer patients were enrolled. Needs and expectations of the caregivers were
      assessed with a French scale of patient expectations for medical consultation,
      the echelle d'attentes en matiere de consultations (EAC), completed by caregivers
      during the inclusion visit. This scale consists in a self-administered 28-item
      questionnaire concerning four main needs: learning skills to improve daily life
      management of their relatives; information regarding the disease; improving
      caregivers' self-confidence; support to improve communication with their
      relatives. RESULTS: The ten items for which more than 40% of caregivers reported
      high or very high expectations referred to two main needs: information regarding
      the disease (treatment, prognosis...) and learning skills in order to improve
      daily life management of their relative. The predominance of such needs was
      observed whatever the relationship between the caregiver and the cared relative
      but seemed to be more pronounced in female spouses and children of patients with
      Alzheimer's disease. CONCLUSIONS: Needs and expectations of Alzheimer's disease
      family caregivers involve two major aspects: first, information regarding the
      disease (treatment, prognosis...) and second, learning skills for improving daily
      life management of their relative. These results suggest that among the various
      available family caregivers support programs, programs providing information,
      education, and practical advice to improve daily life assistance seem to be
      adequate.

PMID- 22595421
TI  - Entrapment of Abeta(1-40) peptide in unstructured aggregates.
AB  - Recognizing the complexity of the fibrillogenesis process provides a solid ground
      for the development of therapeutic strategies aimed at preventing or inhibiting
      protein-protein aggregation. Under this perspective, it is meaningful to identify
      the possible aggregation pathways and their relative products. We found that
      Abeta-peptide dissolved in a pH 7.4 solution at small peptide concentration and
      low ionic strength forms globular aggregates without typical amyloid beta
      conformation. ThT binding kinetics was used to monitor aggregate formation.
      Circular dichroism spectroscopy, AFM imaging, static and dynamic light scattering
      were used for structural and morphological characterization of the aggregates.
      They appear stable or at least metastable with respect to fiber growth, therefore
      appearing as an incidental product in the pathway of fibrillogenesis.

PMID- 22595422
TI  - Fingerprint-based in silico models for the prediction of P-glycoprotein
      substrates and inhibitors.
AB  - P-Glycoprotein (P-gp, ABCB1) plays a significant role in determining the ADMET
      properties of drugs and drug candidates. Substrates of P-gp are not only subject
      to multidrug resistance (MDR) in tumor therapy, they are also associated with
      poor pharmacokinetic profiles. In contrast, inhibitors of P-gp have been
      advocated as modulators of MDR. However, due to the polyspecificity of P-gp,
      knowledge on the molecular basis of ligand-transporter interaction is still poor,
      which renders the prediction of whether a compound is a P-gp substrate/non
      substrate or an inhibitor/non-inhibitor quite challenging. In the present
      investigation, we used a set of fingerprints representing the presence/absence of
      various functional groups for machine learning based classification of a set of
      484 substrates/non-substrates and a set of 1935 inhibitors/non-inhibitors. Best
      models were obtained using a combination of a wrapper subset evaluator (WSE) with
      random forest (RF), kappa nearest neighbor (kNN) and support vector machine
      (SVM), showing accuracies >70%. Best P-gp substrate models were further validated
      with three sets of external P-gp substrate sources, which include Drug Bank (n =
      134), TP Search (n = 90) and a set compiled from literature (n = 76). Association
      rule analysis explores the various structural feature requirements for P-gp
      substrates and inhibitors.

PMID- 22595423
TI  - Protuboxepin A, a marine fungal metabolite, inducing metaphase arrest and
      chromosomal misalignment in tumor cells.
AB  - Previously we reported the identification of a new oxepin-containing
      diketopiperazine-type marine fungal metabolite, named protuboxepin A which showed
      antiproliferative activity in several cancer cell lines. In this study we
      elucidated the mechanism by which protuboxepin A induces cancer cell growth
      inhibition. Here we report that protuboxepin A induced round-up morphology, M
      phase arrest, and an increase in the subG(1) population in tumor cells in a dose
      dependent manner. Our investigations revealed that protuboxepin A directly binds
      to alpha,beta-tubulin and stabilizes tubulin polymerization thus disrupting
      microtubule dynamics. This disruption leads to chromosome misalignment and
      metaphase arrest which induces apoptosis in cancer. Overall, we identified
      protuboxepin A as a microtubule-stabilizing agent which has a distinctly
      different chemical structure from previously reported microtubule inhibitors.
      These results indicate that protuboxepin A has a potential of being a new and
      effective anti-cancer drug.

PMID- 22595424
TI  - Using self-organizing maps to accelerate similarity search.
AB  - While self-organizing maps (SOM) have often been used to map and describe
      chemical space, this paper focuses on their use to accelerate similarity searches
      based on vectors of high-dimensional real-value descriptors for which classical,
      binary fingerprint-based similarity speed-up procedures do not apply. Fuzzy
      tricentric pharmacophore (FPT) and ISIDA substructure counts are herein explored
      examples. Similarity search speed-up was achieved by positioning compounds on a
      SOM, then searching for analogues only in the neurons neighbouring the ones in
      which the query compounds reside. Smaller neighbourhood means shorter virtual
      screening (VS) time, but lower analogue retrieval rates. An enhancement
      criterion, conciliating the opposite trends is defined. It depends on map
      definition and build-up protocol (training set choice, map size, convergence
      criteria,...). The main goal is to discover and validate SOMs of optimal quality
      with respect to this criterion. Increasing the size of the training set beyond a
      certain limit is shown to be unnecessary and even detrimental, suggesting that
      one SOM built on a relatively small but diverse training set may be an effective
      VS enhancer of a much larger database. Also, using an excessively large number of
      training iterations may lead to over-fitting. Gradual training with en-route
      checking of VS enhancement propensity is the best strategy to follow. Maps were
      successfully challenged to accelerate the large-scale VS of 12,000 queries
      against 160,000 compounds, and shown to provide a meaningful mapping of activity
      annotated compounds in chemical space.

PMID- 22595425
TI  - Mild fumarase deficiency and a trial of low protein diet.
AB  - We report clinical findings in a 12-year-old girl with a mild case of fumarase
      deficiency who continues to make progress. She has two novel mutations of the
      fumarase gene [c.521C>G (p.P174R) and c.908T>C (p.L303S)]. A trial of low protein
      diet did not reduce fumaric aciduria.

PMID- 22595427
TI  - Using a photochemical method and chitosan to prepare surface-enhanced Raman
      scattering-active silver nanoparticles.
AB  - In this paper, we report a new strategy for the preparation of surface-enhanced
      Raman scattering (SERS)-active silver nanoparticles (Ag NPs), using a
      photochemical method and the presence of chitosan (Ch). First, Ag substrates were
      subjected to electrochemical oxidation/reduction cycles (ORCs) in deoxygenated
      aqueous solutions containing 0.1 M HNO(3) and 1 g L(-1) Ch (pH 6.9, adjusted by
      adding 1 M NaOH), resulting in Ag(+)-Ch complexes. These substrates were then
      irradiated with UV light at various wavelengths to yield the SERS-active Ag NPs.
      A stronger SERS effect was observed on the SERS-active Ag NPs prepared by using
      UV irradiation at 310 nm. The pH of the solution and the presence of Ch during
      the preparation process both affected the resulting SERS activities.

PMID- 22595428
TI  - Determination of inorganic phosphate by electroanalytical methods: a review.
AB  - Determination of inorganic phosphate is of very high importance in environmental
      and health care applications. Hence knowledge of suitable analytical techniques
      available for phosphate sensing for different applications becomes essential.
      Electrochemical methods for determining inorganic phosphate have several
      advantages over other common techniques, including detection selectivity,
      stability and relative environmental insensitivity of electroactive labels. The
      different electrochemical sensing strategies adopted for the determination of
      phosphate using selective ionophores are discussed in this review. The various
      sensing strategies are classified based on the electrochemical detection
      techniques used viz., potentiometry, voltammetry, amperometry, unconventional
      electrochemical methods etc., The enzymatic sensing of phosphate coupled with
      electrochemical detection is also included. Various electroanalytical methods
      available in the literature are assessed for their merits in terms of
      selectivity, simplicity, miniaturisation, adaptability and suitability for field
      measurements.

PMID- 22595426
TI  - Immunological cell type characterization and Th1-Th17 cytokine production in a
      mouse model of Gaucher disease.
AB  - Gaucher disease is a lysosomal storage disease resulting from insufficient acid
      beta-glucosidase (glucocerebrosidase, GCase, EC 4.2.1.25) activity and the
      resultant accumulation of glucosylceramide. Macrophage (Mphi) lineage cells are
      thought to be the major disease effectors because of their secretion of numerous
      cytokines and chemokines that influence other poorly defined immunological cell
      populations. Increases in several such populations were identified in a Gba1
      mouse model (D409V/null; 9V/null) of Gaucher disease including antigen presenting
      cells (APCs), i.e., Mphi, dendritic cells (DCs), neutrophils (PMNs), and CD4(+) T
      cells. FACS analyses showed increases in these cell types in 9V/null liver,
      spleen lung, and bone marrow. T-cells or APCs enhanced activations were evident
      by positivity of CD40L, CD69, as well as CD40, CD80, CD86, and MHCII on the
      respective cells. Mphi, and, unexpectedly, DCs, PMNs, and T cells, from 9V/null
      mice showed excess glucosylceramides as potential bases for activation of APCs
      and T cells to induce Th1 (IFNgamma, IL12, TNFalpha,) and Th17 (IL17A/F) cytokine
      production. These data imply that excess glucosylceramides in these cells are
      pivotal for activation of APCs and T cell induction of Th1 and Th17 responses and
      PMN recruitment in multiple organs of this model of Gaucher disease.

PMID- 22595429
TI  - Direct rapid analysis of trace bioavailable soil macronutrients by chemometrics
      assisted energy dispersive X-ray fluorescence and scattering spectrometry.
AB  - Precision agriculture depends on the knowledge and management of soil quality
      (SQ), which calls for affordable, simple and rapid but accurate analysis of
      bioavailable soil nutrients. Conventional SQ analysis methods are tedious and
      expensive. We demonstrate the utility of a new chemometrics-assisted energy
      dispersive X-ray fluorescence and scattering (EDXRFS) spectroscopy method we have
      developed for direct rapid analysis of trace 'bioavailable' macronutrients (i.e.
      C, N, Na, Mg, P) in soils. The method exploits, in addition to X-ray
      fluorescence, the scatter peaks detected from soil pellets to develop a model for
      SQ analysis. Spectra were acquired from soil samples held in a Teflon holder
      analyzed using (109)Cd isotope source EDXRF spectrometer for 200 s. Chemometric
      techniques namely principal component analysis (PCA), partial least squares (PLS)
      and artificial neural networks (ANNs) were utilized for pattern recognition based
      on fluorescence and Compton scatter peaks regions, and to develop multivariate
      quantitative calibration models based on Compton scatter peak respectively. SQ
      analyses were realized with high CMD (R(2)>0.9) and low SEP (0.01% for N and Na,
      0.05% for C, 0.08% for Mg and 1.98 MUg g(-1) for P). Comparison of predicted
      macronutrients with reference standards using a one-way ANOVA test showed no
      statistical difference at 95% confidence level. To the best of the authors'
      knowledge, this is the first time that an XRF method has demonstrated utility in
      trace analysis of macronutrients in soil or related matrices.

PMID- 22595430
TI  - Mesoporous TiO2 aerogel for selective enrichment of phosphopeptides in rat liver
      mitochondria.
AB  - The enrichment of low abundance phosphopeptides before MS analysis is a critical
      step for in-depth phosphoproteome research. In this study, mesoporous titanium
      dioxide (TiO(2)) aerogel was prepared by precipitation and supercritical drying.
      The specific surface area up to 490.7 m(2) g(-1) is achieved by TiO(2) aerogel,
      much higher than those obtained by commercial TiO(2) nanoparticles and by the
      latest reported mesoporous TiO(2) spheres. Due to the large specific surface area
      and the mesoporous structure of the aerogel, the binding capacity for
      phosphopeptides is six times higher than that of conventional TiO(2)
      microparticles (173 vs 28 MUmol g(-1)). Because of the good compatibility of
      enrichment procedure with MALDI-TOF-MS and the large binding capacity of TiO(2)
      aerogel, a detection limit as low as 30 amol for analyzing phosphopeptides in
      beta-casein digest was achieved. TiO(2) aerogel was further applied to enrich
      phosphopeptides from rat liver mitochondria, and 266 unique phosphopeptides with
      340 phosphorylation sites, corresponding to 216 phosphoprotein groups, were
      identified by triplicate nanoRPLC-ESI-MS/MS runs, with false-positive rate less
      than 1% at the peptide level. These results demonstrate that TiO(2) aerogel is a
      kind of promising material for sample pretreatment in the large-scale
      phosphoproteome study.

PMID- 22595431
TI  - Selective trace analysis of chloroacetamide herbicides in food samples using
      dummy molecularly imprinted solid phase extraction based on chemometrics and
      quantum chemistry.
AB  - A methodology based on chemometrics and quantum chemistry was proposed to design
      and synthesize dummy molecularly imprinted polymers (DMIPs) capable of extracting
      chloroacetamide herbicides from food samples. Molecular modeling approach in
      conjunction with clustering analysis was used to predict the most suitable dummy
      template. Metolachlor deschloro was selected as the template to synthesize DMIPs,
      which were used as the solid phase extraction (SPE) materials. The selective
      adsorption of DMIPs was evaluated by high performance liquid chromatography
      (HPLC). The retention property of six chloroacetamide herbicides on DMIPs was
      also predicted using clustering analysis. The optimum loading, washing and
      eluting conditions for dummy molecularly imprinted solid phase extraction
      (DMISPE) were established to obtain high selectivity and sensitivity. Water,
      dichloromethane and methanol were chosen as loading, washing and elution solvent,
      respectively. Under optimized DMISPE conditions, recoveries of analytes were in
      the range of 83.4-106.7% with satisfactory precision (RSD% lower than 13%).
      Compared with other commercial SPE columns, DMISPE exhibited selective binding
      properties for chloroacetamide herbicides and the matrix effect was significantly
      decreased.

PMID- 22595432
TI  - Measurement of laser activated electron tunneling from semiconductor zinc oxide
      to adsorbed organic molecules by a matrix assisted laser desorption ionization
      mass spectrometer.
AB  - Measurement of light induced heterogeneous electron transfer is important for
      understanding of fundamental processes involved in chemistry, physics and
      biology, which is still challenging by current techniques. Laser activated
      electron tunneling (LAET) from semiconductor metal oxides was observed and
      characterized by a MALDI (matrix assisted laser desorption ionization) mass
      spectrometer in this work. Nanoparticles of ZnO were placed on a MALDI sample
      plate. Free fatty acids and derivatives were used as models of organic compounds
      and directly deposited on the surface of ZnO nanoparticles. Irradiation of UV
      laser (lambda=355 nm) with energy more than the band gap of ZnO produces ions
      that can be detected in negative mode. When TiO(2) nanoparticles with similar
      band gap but much lower electron mobility were used, these ions were not observed
      unless the voltage on the sample plate was increased. The experimental results
      indicate that laser induced electron tunneling is dependent on the electron
      mobility and the strength of the electric field. Capture of low energy electrons
      by charge-deficient atoms of adsorbed organic molecules causes unpaired electron
      directed cleavages of chemical bonds in a nonergodic pathway. In positive
      detection mode, electron tunneling cannot be observed due to the reverse moving
      direction of electrons. It should be able to expect that laser desorption
      ionization mass spectrometry is a new technique capable of probing the dynamics
      of electron tunneling. LAET offers advantages as a new ionization dissociation
      method for mass spectrometry.

PMID- 22595433
TI  - Small molecule analysis using laser desorption/ionization mass spectrometry on
      nano-coated silicon with self-assembled monolayers.
AB  - Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is an
      emerging technique for the determination of the molecular weight of biomolecules
      and their non-covalent complexes without fragmentation. One problem with this
      technique is the use of excess amounts of matrices, which may produce intense
      fragment ions and/or clusters at low mass ranges between 1 and 800 Da. These
      fragments lead to interference, especially concerning the signals of small target
      molecules. Here, a simple, reusable, and quite inexpensive approach was
      demonstrated to improve the effectiveness of laser desorption/ionization mass
      spectrometry (LDI-MS) analysis, especially for small molecules, without using
      matrix molecules. In this study, substrates with controllable morphologies and
      thicknesses were developed based on the self-assembly of silane molecules on
      silicon surfaces using N-(3-trimethoxysilylpropyl)diethylenetriamine (TPDA) and
      octadecyltrichlorosilane (OTS) molecules. Prepared substrates with nano
      overlayers were successfully used in the analysis of different types of small
      target molecules, namely acrivastine, L-histidine, L-valine, L-phenylalanine, L
      arginine, L-methionine and angiotensin I. Our substrates exhibited clear peaks
      almost without fragmentation for all target molecules, suggesting that these
      surfaces provide a number of important advantages for LDI-MS analysis, such as
      ease of preparation, costs, reusability, robustness, easy handling and preventing
      fragmentation.

PMID- 22595434
TI  - Dual lifetime referenced fluorometry for the determination of doxorubicin in
      urine.
AB  - Dual lifetime referencing (DLR) is introduced as a rapid and self-referenced
      method for measuring the concentration of a fluorescent analyte in solution. The
      fluorescent cancer chemotherapeutic doxorubicin was chosen as a medically
      relevant analyte and blended with a reference dye (Ru(dpp)(3)) that displays
      overlapping excitation and emission spectra. The relative contributions of the
      short-lived (nanoseconds) fluorescent analyte and the long-lived (microseconds)
      reference dye define the observed lifetime. Measuring this lifetime by both
      frequency-domain DLR and time-domain DLR yields similar analytical ranges and
      limits of detection (0.4 MUM). To assess the matrix effect of medical samples,
      the standard addition method was employed to both modes of DLR. Urine was spiked
      with doxorubicin and recovery rates of >=97% were obtained.

PMID- 22595435
TI  - Sequence-specific detection of nucleic acids utilizing isothermal enrichment of G
      quadruplex DNAzymes.
AB  - G-quadruplex DNAzymes are peroxidase-like complexes formed by nucleic acid G
      quadruplexes and hemin. Various chemical sensors and biosensors have been
      developed, based on such DNAzymes. Here we report a novel, specific nucleic acid
      detection method utilizing the isothermal amplification strategy of G-quadruplex
      DNAzymes. In this method, an unlabeled oligonucleotide probe was used. The
      probing sequence of the oligonucleotide was in the form of a stem-loop structure.
      A G-rich sequence, containing three GGG repeats, was linked to the 5'-end of the
      stem-loop structure. In the presence of target, the probing sequence hybridized
      to the target, and a G(n) (n>=2) repeat was extended from its 3'-end. This G(n)
      repeat, together with the three GGG repeats at the 5'-end, folded into a G
      quadruplex, and displayed enhanced peroxidase acitivity upon hemin binding.
      Utilizing the dynamic binding interaction between the probe and its target, the
      enrichment of G-quadruplex DNAzymes was achieved. Using this method, simple,
      rapid and cost-effective nucleic acid detection could be achieved. This method
      displayed high target-length tolerance and good detection specificity; one-base
      mismatch could be judged easily, even by visual inspection. This method may be
      used as an auxiliary tool for amplified detection of specific DNA targets in some
      situations, in which isothermal detection is desirable.

PMID- 22595436
TI  - A new cleanup method of dioxins in sediment using large volume injection gas
      chromatography online coupled with liquid chromatography.
AB  - A new cleanup method was developed and validated for the determination of
      polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) in
      sediment. The sample extract was first treated with sulfuric acid and then
      cleaned up by a large volume injection gas chromatography online coupled with
      liquid chromatography (LVI-GC-LC) system. PCDD/Fs in the extract were separated
      by a GC column (DB-5), selected cut, cool trapped and transferred to a LC column
      (alumina). The fraction of PCDD/Fs eluted from the alumina column was collected
      and concentrated for the instrumental analysis. Under the optimized conditions,
      LVI-GC-LC method achieved the recoveries of 57-102% for 2,3,7,8-substituted
      PCDD/Fs, which met the requirements of US Environmental Protection Agency (EPA)
      Method 1613 and were better than those obtained using the conventional multistep
      column cleanup method. Meanwhile, compared with the conventional method, the
      limit of detection (LOD) values of 2,3,7,8-substituted PCDD/Fs cleaned up by LVI
      GC-LC method were decreased due to the high-efficiency removal of interferents.
      These results suggested that the LVI-GC-LC cleanup method was a promising
      alternative to the multistep cleanup procedure for the determination of dioxins
      in environmental samples.

PMID- 22595437
TI  - Separation and determination of trace uranium using a double-receptor sandwich
      supramolecule method based on immobilized salophen and fluorescence labeled
      oligonucleotide.
AB  - A double-receptor sandwich supramolecule method for the separation and
      determination of trace uranium was proposed in this paper. One receptor is a
      salophen which can react with uranyl to form a uranyl-salophen complex, and
      another receptor is an oligonucleotide which can bind uranyl to form
      oligonucleotide-uranyl-salophen supramolecule. The salophen was immobilized on
      the surface of silica gel particles and used as the solid phase receptor for
      separating uranium from solution. The oligonucleotide was labeled with a
      fluorescent group and used as the labeled receptor for quantitatively analyzing
      uranium. In the procedure of separation and determination, uranyl ion was first
      combined with the solid phase receptor and then conjugated with the labeled
      receptor to form the sandwich-type supramolecule. The labeled receptor in the
      sandwich supramolecule was then eluted and determined by fluorescence analysis.
      The experimental results demonstrate that this method has a number of advantages
      such as high selectivity, excellent pre-concentration capability, high
      sensitivity, good stability and low cost. Under optimal conditions, the linear
      range for the detection of uranium is 0.5-30.0 ng mL(-1) with a detection limit
      of 0.2 ng mL(-1). The proposed method was successfully applied for the separation
      and determination of uranium in real samples with the recoveries of 95.0-105.5%.

PMID- 22595438
TI  - [Flexible bronchoscopy in critical care units].

PMID- 22595439
TI  - [Infectious endocarditis in intensive care medicine].

PMID- 22595440
TI  - L- and D-lactate as biomarkers of arterial-induced intestinal ischemia: an
      experimental study in pigs.
AB  - BACKGROUND: Intestinal ischemia is difficult to diagnose, and search for new
      biomarkers has led to interest in D-lactate, which arises from bacterial
      fermentation in the gastrointestinal tract. METHODS: The superior mesenteric
      artery was clamped in eight pigs for 6 h to induce ischemia of the intestine.
      Eight sham-operated pigs served as controls. Systemic and portal plasma D- and L
      lactate were sampled in 1 h intervals. L-LDH was inactivated prior to D-lactate
      measurement by addition of NaOH. RESULTS: In systemic vein samples, we found a
      significant mean difference in the change of D-lactate from baseline to 6 h
      between the sham and intervention group (.007 +/- .011 mmol/l vs. .030 +/- .013
      mmol/l, respectively) (P = .020). Both systemic and portal circulation levels of
      plasma L-lactate increased significantly between the two groups within an hour.
      The mean difference for L-lactate were -.020 +/- .215 mmol/l and 1.440 +/- 1.454
      mmol/l in the sham and intervention group, respectively (P = .009). CONCLUSION: L
      lactate was found to be a marker of arterial-induced intestinal ischemia in both
      the systemic and portal circulation. There was no significant elevation of D
      lactate at either site during the 6 h of ischemia.

PMID- 22595441
TI  - Causes of in-hospital cardiac arrest and influence on outcome.
AB  - AIM OF THE STUDY: To evaluate the relationship between cause and outcome of in
      hospital cardiac arrest. METHODS: Retrospective analysis of resuscitation data,
      causes of cardiac arrest and outcome with a follow-up to 6 months of a cardiac
      arrest registry in an emergency department of a tertiary care hospital, covering
      a 17.5-year period. RESULTS: Of 1041 patients, 653 were male (63%), the median
      age was 64 years (IQR 53-73), 51% suffered cardiac arrest in the emergency
      department. The first recorded rhythm showed PEA in 432 (41%), ventricular
      fibrillation in 404 (39%) and asystole in 205 (20%) patients. Cardiac arrest of
      cardiac origin occurred in 63% of all patients, with 35% of them due to acute
      myocardial infarction. Non-cardiac causes were mostly due to pulmonary causes
      (15% of all patients). Aortic dissection/rupture, exsanguination, intoxication
      and adverse drug reactions, metabolic, cerebral, sepsis and accidental
      hypothermia each ranged between 1 and 4% of the cohort. Of all patients, 376
      (36%) were discharged in good neurologic condition. Overall, patients with
      cardiac causes had a significantly better outcome than those with non-cardiac
      causes (44% vs. 23%, p<0.01). Patients with pulmonary causes survived in 24%. The
      other subgroups showed widely divergent survival results (3-65%). Patients who
      had suffered cardiac arrest in the emergency department had a better outcome then
      patients of the regular ward or radiology department. CONCLUSION: In hospital
      cardiac arrest is caused mainly by cardiac and pulmonary causes, outcome depends
      on the cause, with a big variability.

PMID- 22595442
TI  - Investigating official records of suicides for research purposes.

PMID- 22595444
TI  - In contrast to conventional inactivated influenza vaccines, 4xM2e.HSP70c fusion
      protein fully protected mice against lethal dose of H1, H3 and H9 influenza A
      isolates circulating in Iran.
AB  - Ideal vaccines against influenza viruses should elicit not only a humoral
      response, but also a cellular response. Mycobacterium tuberculosis HSP70 (mHSP70)
      have been found to promote immunogenic APCs function, elicit a strong cytotoxic T
      lymphocyte (CTL) response, and prevent the induction of tolerance. Moreover, it
      showed linkage of antigens to the C-terminus of mHSP70 (mHSP70c) can represent
      them as vaccines resulted in more potent, protective antigen specific responses
      in the absence of adjuvants or complex formulations. Hence, recombinant fusion
      protein comprising C-terminus of mHSP70 genetically fused to four tandem repeats
      of the ectodomain of the conserved influenza matrix protein M2 (M2e) was
      expressed in Escherichia coli, purified under denaturing condition, refolding,
      and then confirmed by SDS-PAGE, respectively. The recombinant fusion protein,
      4xM2e.HSP70c, retained its immunogenicity and displayed the protective epitope of
      M2e by ELISA and FITC assays. A prime-boost administration of 4xM2e.HSP70c
      formulated in F105 buffer by intramuscular route in mice (Balb/C) provided full
      protection against lethal dose of mouse-adapted H1N1, H3N2, or H9N2 influenza A
      isolates from Iran compared to 0-33.34% survival rate of challenged unimmunized
      and immunized mice with the currently in use conventional vaccines designated as
      control groups. However, protection induced by immunization with 4xM2e.HSP70c
      failed to prevent weight loss in challenged mice; they experienced significantly
      lower weight loss, clinical symptoms and higher lung viral clearance in
      comparison with protective effects of conventional influenza vaccines in
      challenged mice. These data demonstrate that C-terminal domain of mHSP70 can be a
      superior candidate to deliver the adjuvant function in M2e-based influenza A
      vaccine in order to provide significant protection against multiple influenza A
      virus strains.

PMID- 22595446
TI  - Efficacy of metal and plastic stents in unresectable complex hilar
      cholangiocarcinoma: a randomized controlled trial.
AB  - BACKGROUND: Endoscopic biliary stent drainage is effective in the palliative
      treatment of patients with hilar cholangiocarcinoma (HCA). However, no randomized
      controlled trial comparing the efficacy of the self-expandable metal stent (SEMS)
      and the plastic stent (PS) in patients with unresectable complex HCA is
      available. OBJECTIVE: To compare the successful drainage rates of endoscopic
      SEMSs and PSs. DESIGN: A single-center, open-label randomized controlled trial.
      SETTING: University hospital in KhonKaen, Thailand. PATIENTS: One hundred eight
      patients with unresectable complex, Bismuth type II-IV HCA. INTERVENTIONS:
      Endoscopic retrograde cholangiography with unilateral SEMS or PS insertion. MAIN
      OUTCOME MEASUREMENTS: Successful drainage rate. LIMITATIONS: Diagnosis of HCA was
      made by clinical presentations, imaging studies, and clinical outcome during
      follow-up. RESULTS: One hundred eight patients were randomly allocated to the
      SEMS and PS groups. Intention-to-treat analysis revealed that the successful
      drainage rate in the SEMS group was higher than in the PS group (70.4% vs 46.3%,
      P = .011). The median survival times were 126 and 49 days, respectively, in the
      SEMS and PS groups. The overall survival rates of the patients in both groups
      were statistically different by log-rank test (P = .002). CONCLUSIONS: Endoscopic
      biliary drainage with the SEMS provides better adequacy of drainage and longer
      survival compared with the PS in patients with unresectable complex HCA.

PMID- 22595445
TI  - Differential assembly of Hepatitis B Virus core protein on single- and double
      stranded nucleic acid suggest the dsDNA-filled core is spring-loaded.
AB  - Hepatitis B Virus (HBV) cores assemble on viral RNA, which is reverse transcribed
      within the core to the partially dsDNA genome of mature HBV. However,
      constraining dsDNA, a stiff polymer, within a core necessarily requires far
      greater capsid stability than constraining ssRNA. We hypothesized that, unlike
      ssRNA, dsDNA would be a poor substrate for assembly. We examined titrations of
      ssDNA and dsDNA with purified HBV core protein, Cp183, by EMSA, EM, DLS, and
      etheno-DNA fluorescence. Cp183 bound ssDNA with high affinity to form virus-like
      capsids. However, Cp183 bound dsDNA poorly, forming a mixture of irregular
      complexes. Nonetheless, we observed some normal cores in dsDNA assembly
      reactions, indicating that the energy required to bend DNA could be similar to
      the protein-protein association energy. This similarity of energies suggests that
      dsDNA stresses mature HBV cores, in agreement with calculation, which may be the
      basis for the virus maturation signal and DNA release.

PMID- 22595447
TI  - The 2012 Canadian hypertension education program recommendations for the
      management of hypertension: blood pressure measurement, diagnosis, assessment of
      risk, and therapy.
AB  - We updated the evidence-based recommendations for the diagnosis, assessment,
      prevention, and treatment of hypertension in adults for 2012. The new
      recommendations are: (1) use of home blood pressure monitoring to confirm a
      diagnosis of white coat syndrome; (2) mineralocorticoid receptor antagonists may
      be used in selected patients with hypertension and systolic heart failure; (3) a
      history of atrial fibrillation in patients with hypertension should not be a
      factor in deciding to prescribe an angiotensin-receptor blocker for the treatment
      of hypertension; and (4) the blood pressure target for patients with nondiabetic
      chronic kidney disease has now been changed to < 140/90 mm Hg from < 130/80 mm
      Hg. We also reviewed the recent evidence on blood pressure targets for patients
      with hypertension and diabetes and continue to recommend a blood pressure target
      of less than 130/80 mm Hg.

PMID- 22595448
TI  - The obesity epidemic and its impact on hypertension.
AB  - Global obesity rates have increased steadily in both developed and emerging
      countries over the past several decades with little signs of slowing down. Over
      1.5 billion people worldwide are overweight or obese and over 40 million children
      under the age of 5 are overweight. Obesity is associated with increased
      morbidity, disability, and premature mortality from cardiovascular disease,
      diabetes, cancers, and musculoskeletal disorders. The personal and societal
      health and economic burden of this preventable disease pose a serious threat to
      our societies. Obesity is a major risk factor for hypertension and cardiovascular
      disease. Weight loss, through health behaviour modification and dietary sodium
      restriction, is the cornerstone in the treatment of obesity-related hypertension.
      Pharmacotherapy and bariatric surgery for obesity are adjunctive measures when
      health behaviour interventions fail to achieve the body weight and health
      targets. Successful management of overweight and obese persons requires a
      comprehensive, multifaceted framework that integrates population health, public
      health, and medical health models to dismantle the proximal and distal drivers of
      the obesogenic environment in which we live. Prevention of obesity is no longer a
      lofty but rather necessary goal that urgently calls for action from governments
      at all levels, in conjunction with all public and private sector stakeholders, in
      order to combat a serious and growing public health concern.

PMID- 22595449
TI  - The evolving role of beta-adrenergic receptor blockers in managing hypertension.
AB  - beta-Adrenergic blocking agents (or beta-blockers) have been widely used for the
      treatment of hypertension for the past 50 years, and continue to be recommended
      as a mainstay of therapy in many national guidelines. They have also been used in
      a variety of cardiovascular conditions commonly complicating hypertension,
      including angina pectoris, myocardial infarction (MI), acute and chronic heart
      failure, as well as conditions like essential tremor and migraine. Moreover, they
      have played a primary role in controlling blood pressure in patients with these
      specific comorbidities and in reducing cardiovascular risk with regard to the
      composite outcome of death, stroke, and MI among patients younger than 60 years
      of age. However, in patients 60 years of age or older, beta-blockers were not
      associated with significantly lower rates of MI, heart failure or death, and
      demonstrated higher rates of stroke compared with other first-line therapies.
      Consequently, the Canadian Hypertension Education Program recommends the use of
      beta-blockers as first-line therapy in hypertensive patients younger than 60
      years of age but not for those age 60 and older, with the exception of patients
      with concomitant beta-blocker-requiring cardiac diseases. Several reports suggest
      that the lack of consistent outcome data may relate to the use of traditional
      beta-blockers such as atenolol and their ability only to reduce cardiac output,
      without beneficial effect on peripheral vascular resistance. The present report
      will describe the clinically relevant mechanisms of action of beta-blockers,
      their pharmacological differences, their metabolic effects, and their usefulness
      in patients with hypertension.

PMID- 22595450
TI  - Folate and vitamin B12 deficiency and hyperhomocysteinemia promote oxidative
      stress in adult type 2 diabetes.
AB  - OBJECTIVE: The purpose of this study was to examine the status of folate and
      vitamin B12 (B12) in relation to serum homocysteine (HCY) and oxidative stress
      indices in patients with type 2 diabetes (T2DM). METHODS: This case-control study
      involved 100 Omani adults (50 patients newly diagnosed with T2DM and 50 age- and
      gender-matched healthy controls). Several parameters were investigated, including
      dietary intake and biochemical assessments of folate, B12, HCY, oxidative stress
      markers (glutathione and total antioxidant status), and antioxidant enzymes
      (superoxide dismutase, glutathione peroxidase, and catalase). RESULTS: Low serum
      levels of folate, B12, and hyperhomocysteinemia were prevalent in patients with
      T2DM compared with controls. Oxidative stress was evident in patients with T2DM
      as indicated by low serum levels of glutathione, total antioxidant status, and
      impaired antioxidant enzymatic activities (superoxide dismutase, glutathione
      peroxidase, and catalase). CONCLUSION: The low intake of folate and B12 is
      associated with low serum levels of these two nutrients and hyperhomocysteinemia
      in Omani adults with T2DM.

PMID- 22595451
TI  - Quercetin alleviates hypercholesterolemic diet induced inflammation during
      progression and regression of atherosclerosis in rabbits.
AB  - OBJECTIVE: Recent advances have established a fundamental role for inflammation
      in mediating all stages of atherosclerosis, from initiation through progression.
      Quercetin may be a powerful bioactive constituent of the human diet, as a free
      radical scavenging agent and through interactions with various endogenous
      proteins. The present study focused on the effect of quercetin on inflammation
      induced by a hypercholesterolemic diet (HCD) in rabbits. METHODS: The animals
      were subjected to two different experiments, atherosclerotic progression and
      regression. In the atherosclerotic progression study, quercetin (25 mg/kg of body
      weight) was administered with the HCD for 90 d. In the atherosclerotic regression
      study, the animals were fed with the HCD for 90 d and then supplemented with
      quercetin (25 mg/kg of body weight) for another 90 d. The inflammatory enzyme
      activities were examined and a histopathologic examination of the aorta was
      performed. RESULTS: In the atherosclerotic progression study, quercetin
      coadministered with the HCD significantly decreased the activities of
      inflammatory enzymes such as cyclooxygenase, lipoxygenases (LOX) such as 5-LOX
      and 12-LOX in monocytes, nitric oxide synthase activity in the plasma,
      myeloperoxidase activity in the aorta, and the level of C-reactive protein in
      serum. In the regression study, quercetin administration significantly decreased
      the increased activities of inflammatory mediators such as cyclooxygenase, 5-LOX,
      12-LOX, myeloperoxidase, and nitric oxide synthase and the serum level of C
      reactive protein in HCD-fed rabbits compared with regression control rabbits.
      This effect was confirmed by histopathologic examination of the aorta.
      CONCLUSION: This study demonstrates that quercetin modulates the deleterious
      inflammatory effects induced by an HCD in vivo in rabbits, suggesting its
      beneficial effect in decreasing inflammation in atherosclerotic progression and
      regression.

PMID- 22595452
TI  - Colonisation and infection of the paranasal sinuses in cystic fibrosis patients
      is accompanied by a reduced PMN response.
AB  - BACKGROUND: We studied whether the sinuses might be foci for Pseudomonas
      aeruginosa lung infection. METHODS: Endoscopic Sinus Surgery was performed in 78
      CF patients; PFGE was used for bacterial genotyping. Material from sinuses and
      lungs were Gram-stained to detect biofilms. Immunoglobulins were measured in
      serum and saliva. RESULTS: When P. aeruginosa was cultured simultaneously from
      the sinuses and the lungs they were genetically identical in 38 of the 40
      patients (95%). In the sinuses, P. aeruginosa formed biofilms with minimal
      cellular inflammation, probably because of a significantly higher local
      production of secretory IgA compared with IgG (p<0.001). CONCLUSIONS: We have
      shown that P. aeruginosa form biofilm in the sinuses, which constitute an
      important bacterial reservoir for subsequent lung infection. The high amount of
      IgA in the upper airways probably protects P. aeruginosa from the inflammatory
      immune system, and they can proceed unnoticed into a permanent infectious focus
      that cannot be eradicated with antibiotics.

PMID- 22595453
TI  - First Australian transapical mitral valve-in-valve implant for a failed mitral
      bioprosthesis: how to do it.
AB  - Transcatheter aortic valve replacements lower mortality in patients not suitable
      for surgical valve replacement compared to conservative treatment. Transcatheter
      valve-in-valve implants have been shown to be feasible in failed bioprostheses in
      aortic, mitral, pulmonary and tricuspid positions. We report the first
      Australasian experience of a transapical mitral valve-in-valve placement with an
      Edwards Sapien((r)) transcatheter valve for a failed mitral bioprosthesis,
      focussing on the technical aspects of this novel procedure. Whilst the evidence
      for this niche indication is limited currently to case reports and case series,
      further evaluation of its long term outcomes may justify its use in this
      particularly high risk group of re-do sternotomy patients.

PMID- 22595454
TI  - Geographic, ethnic and socioeconomic factors influencing access to implantable
      cardioverter defibrillators (ICDs) in New Zealand.
AB  - BACKGROUND: We examined equity of access to implanted cardioverter defibrillators
      (ICDs) in New Zealand in 2010 by district health board (DHB), ethnicity and
      socioeconomic status. METHODS: All new ICD recipients in 2010 were examined
      according to home district health board, ethnicity according to the national
      health database, and socioeconomic status using the NZDep index. RESULTS: During
      2010, 352 new ICDs were implanted nationwide, giving an overall implantation rate
      of 80.6/million. However, implant rates varied significantly across the 20 DHBs
      with the highest implant rate observed in Tairawhiti at 192.3/million, and the
      lowest at 22/million in the Nelson region. There was also significant variation
      in implant rate by ethnicity, with Maori ethnicity at an implant rate of
      114/million, European patients at 83/million, Pacific Island patients at
      47/million and Asian patients an implant rate of 32/million. There was no
      significant difference in number of implants by socioeconomic decile.
      CONCLUSIONS: The variance in implantation rate by district health board and by
      ethnicity suggests that access to ICD therapy is not equitable in New Zealand.
      Investigation into causes of inequity of access is required.

PMID- 22595455
TI  - Estimating the prevalence of active Helicobacter pylori infection in a rural
      community with global positioning system technology-assisted sampling.
AB  - We investigated a possible outbreak of H. pylori in a rural Northern Plains
      community. In a cross-sectional survey, we randomly sampled 244 households from a
      geocoded emergency medical system database. We used a complex survey design and
      global positioning system units to locate houses and randomly selected one
      eligible household member to administer a questionnaire and a 13C-urea breath
      test for active H. pylori infection (n = 166). In weighted analyses, active H.
      pylori infection was detected in 55.0% of the sample. Factors associated with
      infection on multivariate analysis included using a public drinking-water supply
      [odds ratio (OR) 12.2, 95% confidence interval (CI) 2.9-50.7] and current
      cigarette smoking (OR 4.1, 95% CI 1.7-9.6). People who lived in houses with more
      rooms, a possible indicator of decreased crowding in the home, were less likely
      to have active H. pylori infections (OR 0.7, 95% CI 0.5-0.9 for each additional
      room).

PMID- 22595456
TI  - Regulation of lung surfactant secretion by microRNA-150.
AB  - P2X7 receptor (P2X7R) is a purinergic ion-channel receptor. We have previously
      shown that the activation of P2X7R in alveolar type I cells stimulates surfactant
      secretion in alveolar type II cells. In this study, we determined whether miR-150
      regulates P2X7R-mediated surfactant secretion. The miR-150 expression level in
      alveolar type II cells was much higher than alveolar type I cells, which was
      inversely correlated with the P2X7R protein level. An adenovirus expressing miR
      150 significantly reduced the P2X7R protein expression in E10 cells, an alveolar
      type I cell line. Furthermore, pre-treatment of E10 cells with the adenovirus
      reduced the surfactant secretion induced by E10 cell conditioned medium. Our
      study demonstrates that miR-150 regulates surfactant secretion through P2X7R.

PMID- 22595457
TI  - S-layer proteins of Lactobacillus acidophilus inhibits JUNV infection.
AB  - It has been previously described that S-layer binds to the C-type lectin DC
      specific ICAM-3-grabbing nonintegrin (DC-SIGN, CD209). It was also shown that DC
      SIGN is a cell-surface adhesion factor that enhances viral entry of several virus
      families. Among those, Junin virus (JUNV) entry is enhanced in cells expressing
      DC-SIGN and for that reason surface-layer protein (S-layer) of Lactobacillus
      acidophilus ATCC 4365 was evaluated as a possible JUNV inhibitor. Experiments
      using 3T3 cells stably expressing DC-SIGN, showed an almost complete inhibition
      of JUNV infection when they were treated with S-layer in a similar extend as the
      inhibition shown by mannan. However no inhibition effect was observed in 3T3 wild
      type cells or in 3T3 cells expressing liver/lymph node-specific ICAM-3 grabbing
      nonintegrin (L-SIGN or DC-SIGNR or CD209L). Treatments with S-layer during
      different times in the infection demonstrated that inhibition was only observed
      when S-layer was presented in early stages of the viral infection. This
      inhibition does not involve the classic recognition of mannose by this C-type
      lectin as the S-layer showed no evidence to be glycosylated. In fact, the highly
      basic nature of the S-layer (pI>9.5) seems to be involved in electrostatic
      interactions between DC-SIGN and S-layer, since high pH abolished the inhibitory
      effect on infection cause by the S-layer. In silico analysis predicts a Ca(2+)
      dependant carbohydrate recognition domain in the SlpA protein. This novel
      characteristic of the S-layer, a GRAS status protein, contribute to the pathogen
      exclusion reported for this probiotic strain and may be applied as an antiviral
      agent to inhibit several kinds of viruses.

PMID- 22595458
TI  - Targeted Casp8AP2 methylation increases drug resistance in mesenchymal stem cells
      and cancer cells.
AB  - Casp8AP2 contains a FLASH functional domain and is critical for the formation of
      death complex and the relay of death signal into the cells. Genetic defects in
      Casp8AP2 are associated with several diseases. A CpG island within the Casp8AP2
      promoter is differentially regulated during somatic stem cell differentiation,
      and aberrant DNA methylation within the Casp8AP2 promoter has been reported in
      cancers. We hypothesized that abnormal DNA methylation of Casp8AP2 promoter might
      contribute to prolonged cellular survival or drug resistance in cancer. The
      epigenetic state within the Casp8AP2 promoter was then determined in different
      cancer cell lines and patient samples by methylation-specific PCR. Targeted
      Casp8AP2 methylation within normal and tumor cells was performed to see whether
      methylation promoted drug resistance. We found differential Casp8AP2 methylation
      among the normal and tumoral samples. Global demethylation in a platinum drug
      resistant human gastric cancer cell line reversed Casp8AP2 methylation and
      diminished drug resistance. Targeted methylation of the Casp8AP2 promoter in
      somatic stem cells and cancer cells increased their resistance to drugs including
      platinum drugs. These data demonstrate that methylation within the Casp8AP2
      promoter correlates with the development of drug resistance and might serve as a
      biomarker and treatment target for drug resistance in cancer cells.

PMID- 22595459
TI  - Low voltage and variable-pressure scanning electron microscopy of fractured
      composites.
AB  - Uncoated fracture surfaces of carbon-epoxy composites are investigated using a
      variable-pressure environmental scanning electron microscope (VP-ESEM), under
      optimized conditions for topographic description, image quality and sample
      preservation. Always using freeware or open source programs, parameters for low
      voltage and low vacuum are stipulated with the support of Monte Carlo simulations
      combined to topographic measurements, tailoring the VP-ESEM setup for
      visualization of fine relief details. Based on topographic information from
      atomic force microscope (AFM) images, finest fracture steps were measured. These
      were the references to optimize and define boundaries for applied beam voltages
      and chamber pressures, restricted by the beam penetration depth and gas-electron
      interactions, guided by Monte Carlo simulations and signal-to-noise measurements.
      For VP mode, ideal chamber pressure was found around 30-40Pa at 3keV beam voltage
      and 6mm working distance. Lower pressures will cause noise due to electron
      charging and gas excess provokes resolution degradation and noise due to positive
      charging and electron beam scattering, raising the skirt radius. When a larger
      working distance is necessary, it can be compensated by adjusting the detector
      bias and the probe current, or even lowering chamber pressure, but the signal-to
      noise ratio will certainly change. Monte Carlo simulations provided a good
      approach to optimize imaging conditions under low vacuum and low voltage for
      fractographic analysis of carbon-epoxy composites.

PMID- 22595460
TI  - Approaches for ultrafast imaging of transient materials processes in the
      transmission electron microscope.
AB  - The growing field of ultrafast materials science, aimed at exploring short-lived
      transient processes in materials on the microsecond to femtosecond timescales,
      has spawned the development of time-resolved, in situ techniques in electron
      microscopy capable of capturing these events. This article gives a brief overview
      of two principal approaches that have emerged in the past decade: the
      stroboscopic ultrafast electron microscope and the nanosecond-time-resolved
      single-shot instrument. The high time resolution is garnered through the use of
      advanced pulsed laser systems and a pump-probe experimental platforms using laser
      driven photoemission processes to generate time-correlated electron probe pulses
      synchronized with laser-driven events in the specimen. Each technique has its
      advantages and limitations and thus is complementary in terms of the materials
      systems and processes that they can investigate. The stroboscopic approach can
      achieve atomic resolution and sub-picosecond time resolution for capturing
      transient events, though it is limited to highly repeatable (>10(6) cycles)
      materials processes, e.g., optically driven electronic phase transitions that
      must reset to the material's ground state within the repetition rate of the
      femtosecond laser. The single-shot approach can explore irreversible events in
      materials, but the spatial resolution is limited by electron source brightness
      and electron-electron interactions at nanosecond temporal resolutions and higher.
      The first part of the article will explain basic operating principles of the
      stroboscopic approach and briefly review recent applications of this technique.
      As the authors have pursued the development of the single-shot approach, the
      latter part of the review discusses its instrumentation design in detail and
      presents examples of materials science studies and the near-term instrumentation
      developments of this technique.

PMID- 22595461
TI  - Minimal access and standard cochlear implantation: a comparative study.
AB  - OBJECTIVE: To compare the operative times and complications between patients who
      underwent minimal access cochlear implantation and standard technique cochlear
      implantation. METHODS: Patients who underwent unilateral cochlear implantation by
      a single surgeon from 2001 to 2010. The minimal access technique of an
      approximately 2.5-3 cm post-auricular incision with creation of subperiosteal
      pocket for the device was compared to the longer standard "S" incision into the
      scalp (~8-10 cm) with bone well creation and suture fixation. Outcomes include
      operative times and complications. RESULTS: There were 122 unilateral implants,
      73 (59.8%) in the minimal access group and 49 (40.2%) in the standard group. Mean
      total time in the operating room was lower in the minimal access group compared
      to the standard group (200+/-31 vs. 255+/-49 min, p<.0001) as well as mean
      operative time (149.5+/-28 vs. 200+/-45 min, p<.0001 respectively). There were 17
      complications in the entire cohort with 8 and 9 complications in the minimal and
      standard groups respectively. Of the 17 complications, 12 were surgical technique
      specific. Although it appeared that there were higher rates of major, technique
      specific, and overall complications in the standard access group, these
      differences did not reach statistical significance. CONCLUSIONS: Patients
      undergoing minimal access cochlear implantation require shorter operative times
      when compared to the standard access cochlear implantation. In addition, low
      complication rates are observed for major, technique-specific, and overall
      complications. Minimal access cochlear implantation may be considered an
      equivalent and potentially superior technique.

PMID- 22595462
TI  - The effect of paracetamol, metamizole sodium and ibuprofen on postoperative
      hemorrhage following pediatric tonsillectomy.
AB  - OBJECTIVE: To determine the risk of postoperative hemorrhage associated with the
      use of analgesic drugs including paracetamol, metamizole sodium and ibuprofen
      after pediatric tonsillectomy. PATIENTS AND METHODS: Three hundred and forty
      consecutive children with recurrent tonsillitis and/or obstructive symptoms were
      included in the study. Children were divided into three groups based on the drugs
      used for postoperative pain relief. Each group received paracetamol, metamizole
      sodium and ibuprofen following the surgery. The study of population was compared
      respect to postoperative bleeding. Chi-square test was used for statistical
      analysis. RESULTS: A total of 115 patients received ibuprofen, 115 patients were
      given metamizole sodium and 110 patients were given paracetamol.
      Posttonsillectomy hemorrhage occurred in fourteen (4.11%) children, consisting of
      primary hemorrhage in two patients and secondary hemorrhage in twelve patients.
      While 6 of 115 children (5.21%) who were given ibuprofen had postoperative
      hemorrhage, 4 of 115 children (3.47%) in metamizole sodium group and 4 of 110
      patients (3.63%) in paracetamol group had hemorrhage. There was no significant
      difference with respect to hemorrhage rates between these three groups (p<0.05).
      CONCLUSION: In our study we could not show significant risk of hemorrhage after
      using of ibuprofen, metamizole sodium and paracetamol administration and they can
      be used safely for posttonsillectomy pain.

PMID- 22595463
TI  - Pediatric septoplasy: a review of the literature.
AB  - OBJECTIVES: Controversy has surrounded the procedure of pediatric septoplasty
      since the 1950s due to concerns over an adverse effect on nasal and facial
      growth. However, more recent evidence has demonstrated that septoplasty can be
      safely performed without affecting nasal and facial development in the
      appropriately selected pediatric patient. The purpose of this article is to
      establish the impact of pediatric septoplasty on nasal and facial growth and
      review the clinical indications and evidence for timing of surgery according to
      the most recent literature. METHODS: A structured review of the PubMed, Ovid
      Medline and Cochrane Collaboration databases (Cochrane Central Register of
      Controlled Trials, Cochrane Database of Systemic Reviews) was undertaken, using
      the terms: pediatric, childhood, septoplasty, nasal septum, indications, nasal
      growth and facial growth. RESULTS: Three long term follow up studies using
      anthropometric measurements were identified which concluded that pediatric
      septoplasty does not interfere with normal nasal or facial development. A further
      similar study concluded that external septoplasty does not affect most aspects of
      nasal and facial growth, but may negatively influence growth of the nasal dorsum.
      Furthermore, one study demonstrated that a group of children with symptomatic
      uncorrected deviated nasal septum had a statistically significant increased
      occurrence of facial and dental anomalies compared with age and sex matched
      controls, therefore supporting a role for septoplasty. CONCLUSIONS: Evidence
      exists to support that pediatric septoplasty can be performed without affecting
      most aspects of nasal and facial growth. Furthermore, not performing or delaying
      septoplasty when indicated may adversely affect nasal and facial growth with
      compounding adverse effects in terms of deformity and asymmetry. Despite the
      majority advocating the timing of septal surgery to be 6 years and older, more
      clinical studies are required that may provide further evidence for correction of
      septal deviations in younger children, perhaps even at birth.

PMID- 22595464
TI  - Systematic association analysis of microRNA machinery genes with schizophrenia
      informs further study.
AB  - microRNAs (miRNAs) play a vital role in development via the post-transcriptional
      regulation of most genes. Variation in the miRNA machinery pathway proteins which
      mediate the biogenesis, maturation, transportation, and functioning of miRNAs
      might be relevant to human traits. In this work, we explored the role of 59 miRNA
      machinery genes in schizophrenia (SZ). Association analysis of 967 single
      nucleotide polymorphisms within these genes detected that an intronic
      polymorphism of EIF4ENIF1, rs7289941, was significantly associated with SZ
      (P=4.10E-5). We failed to replicate this result in a validation sample comprising
      1027 healthy controls and 1012 SZ cases, and the combined data yielded nominal
      significance (P=0.013). We conducted a gene-based association analysis using
      VEGAS and SKAT, and found seven associated genes in total, including EIF4ENIF1,
      PIWIL2, and DGCR8, but none survived correction for multiple testing. Taken
      together, our data do not provide strong support for the association of common
      variants within miRNA machinery genes with SZ in the Han Chinese population, but
      implicate several promising candidate genes for further research.

PMID- 22595465
TI  - Antinociceptive effects of galanin in the nucleus accumbens of rats.
AB  - It has been demonstrated that galanin plays important roles in the modulation of
      nociceptive information in rats. The present study is performed to investigate
      the regulating role of galanin in nociception in the nucleus accumbens (NAc) of
      rats. Intra-NAc administration of galanin induces dose-dependent increases in the
      hindpaw withdrawal latency (HWL) to noxious thermal and mechanical stimulation in
      rats. Furthermore, the galanin-induced antinociceptive effects are blocked by
      following intra-NAc injection of the galanin receptor antagonist galantide. The
      results demonstrate that galanin induces antinociceptive effects in the NAc of
      rats, and galanin receptors are involved in the galanin-induced antinociception
      effects.

PMID- 22595466
TI  - Successful postoperative activation of an adjustable annuloplasty ring (MiCardia)
      in recurrent ischemic mitral valve regurgitation.
AB  - We report the case of a 73-year-old patient with severe ischemic mitral
      regurgitation (MR). She subsequently underwent combined coronary artery
      revascularization and mitral valve annuloplasty using the adjustable enCorSQ
      device (MiCardia Corporation, Irvine, CA). Three months later she experienced
      recurrent symptomatic severe MR. Accessing the subcutaneous lead, activation and
      downsizing of the device within 45 seconds resulted in trace MR. The result was
      unchanged 1 month later.

PMID- 22595467
TI  - Tailored thoracomyoplasty as a valid treatment option for chronic postlobectomy
      empyema.
AB  - BACKGROUND: Chronic post-lobectomy empyema is rare but may require space
      obliteration for infection control. We report our experience by using a tailored
      thoracomyoplasty for this specific indication with respect to infection control
      and functional outcome. METHODS: We retrospectively analyzed 17 patients (11 men,
      6 women) with chronic postlobectomy empyema who were treated by thoracomyoplasty
      in our institution between 2000 and 2011. All patients underwent an initial
      treatment attempt by use of chest tube drainage and antibiotics except those with
      suspicion of pleural aspergillosis (n=6). In 5 patients, bronchus stump
      insufficiency was identified at preoperative bronchoscopy. A tailored
      thoracoplasty was combined with a serratus anterior-rhomboid myoplasty, which
      also served to close a bronchopleural fistula, if present. The first rib was
      resected in 11 of 17 patients. RESULTS: The 90-day mortality was 11.7%.
      Thoracomyoplasty was successful in all surviving patients with respect to
      infection control, space obliteration, and definitive closure of bronchopleural
      fistula, irrespective of the type of infection, the presence of a bronchopleural
      fistula, or whether a first rib resection was performed. Postlobectomy pulmonary
      function testing before and after thoracoplasty revealed a mean predicted FEV(1)
      of 63.0%+/-8.5% and 51.5%+/-4.2% (p=0.01) and a mean predicted DLCO of 59.8%+/
      11.6% and 54.5%+/-12.5%, respectively. Postoperative shoulder girdle dysfunction
      and scoliosis were prevented in patients willing to undergo intense
      physiotherapy. CONCLUSIONS: Tailored thoracomyoplasty represents a valid option
      for patients with chronic postlobectomy empyema without requiring a preceding
      open window thoracostomy. Space obliteration and infection control were equally
      obtained with and without first rib resection.

PMID- 22595468
TI  - Targeting landing zone 0 by total arch rerouting and TEVAR: midterm results of a
      transcontinental registry.
AB  - BACKGROUND: Landing zone 0, defined as a proximal landing zone in the ascending
      aorta, remains the last frontier to be taken. Midterm results of total arch
      rerouting and thoracic endovascular aortic repair (TEVAR) extending into landing
      zone 0 remain to be determined. METHODS: From 2003 to 2011, 66 patients (mean
      age, 70 years; 68% men) presenting with pathologic conditions affecting the
      aortic arch (atherosclerotic aneurysms [n = 48], penetrating ulcers [n = 6], type
      B dissections [n = 6], type B after type A dissections [n = 5], and anastomotic
      aneurysm [n = 1]) were treated in 5 participating centers. Of these 66 patients,
      only 12% would have been deemed suitable for any kind of conventional surgical
      repair because of multisegmental aortic disease or comorbidities. RESULTS: In
      hospital mortality was 9%. Retrograde type A dissection was observed in 3% of
      patients. The assisted type I and type III endoleak rate was 0%. Stroke was seen
      in 5% of patients. Permanent paraplegia was observed in 3% of those studied.
      Median follow-up was 25 months (8-41 months). There was 1 late type Ib endoleak,
      which was followed by watchful waiting. Five-year survival was 72%. Five-year
      aorta-related survival was 96%. No aorta-related reintervention had to be
      performed in the segments treated. CONCLUSIONS: Midterm results of total arch
      rerouting and TEVAR extending into landing zone 0 are excellent in regard to
      aorta-related survival and freedom from aorta-related reintervention. Retrograde
      type A dissection, potentially related to compliance mismatch between the
      ascending aorta and the stent-graft, warrants further attention. Extended
      application of this strategy augments therapeutic options in a group of patients
      who are not suitable candidates for conventional therapy.

PMID- 22595469
TI  - Early stenosis of stentless aortic valve prosthesis: a word of caution.
AB  - Early stenosis of stentless bioprosthetic valves is rarely reported. In this
      report, we discuss a 75-year-old woman who presented with signs of congestive
      heart failure 5 months after a stentless aortic valve replacement, complicated by
      postoperative heparin-induced thrombocytopenia. Intraoperative findings were
      highly unusual, consisting of a fibrous band in the subvalvular apparatus linking
      the interventricular septum to the free wall of the left ventricle, resulting in
      significant left ventricular outflow tract obstruction. The possible causes of
      the fibrous band are discussed.

PMID- 22595470
TI  - Correspondence between first-trimester fasting glycaemia, and oral glucose
      tolerance test in gestational diabetes diagnosis.
AB  - AIM: To evaluate the correspondence between first-trimester fasting glycaemia and
      the results of the OGTT in diagnosing gestational diabetes (GDM). METHODS: The
      medical records of all consecutive women who had undergone a diagnostic OGTT,
      performed according to the IADPSG, during the past year were retrospectively
      reviewed. All first-trimester fasting glucose values greater or equal to 5.1
      mmol/L (92 mg/dL), recommended as a diagnostic value, were also verified for each
      patient in this cohort. Moreover, a ROC curve and a multiple logistic-regression
      model were constructed to calculate the predictive capability of this cut-off
      value in diagnosing GDM. RESULTS: In our population of 738 eligible pregnant
      women, an 11.9% prevalence of GDM was revealed by OGTT. However, when the first
      trimester fasting glucose value for each patient was retrospectively considered,
      there were a further 29 patients who should have been diagnosed as GDM cases
      (glycaemia >= 5.1 mmol/L), although their OGTT was normal. Yet, when the value of
      fasting glucose was considered not diagnostic, but only predictive, an AUC of
      0.614 (95% CI: 0.544-0.684) and an aOR of 7.1 (95% CI: 3.8-13.1) was obtained in
      these patients compared with the reference group (fasting glucose < 5.1 mmol/L).
      CONCLUSION: There was no complete correspondence in diagnosing GDM between the
      first-trimester fasting glucose value and the results of a 2-h 75-g OGTT
      performed early in the third trimester. However, albeit not diagnostic, a fasting
      glucose value greater or equal to 5.1 mmol/L may be considered a highly
      predictive risk factor for GDM.

PMID- 22595471
TI  - Campylobacter jejuni cutaneous infection in a patient with graft versus host
      disease.

PMID- 22595472
TI  - [Reply to letter: Do primary care doctors empathise with pregnant women?].

PMID- 22595473
TI  - [Towards an assesment of the instrumental abilities of the elderly validated in
      our environment].

PMID- 22595474
TI  - Seminars in Vascular Surgery. Introduction.

PMID- 22595475
TI  - The current role of operative venous thrombectomy in deep vein thrombosis.
AB  - Patients with acute iliofemoral deep vein thrombosis suffer the most severe post
      thrombotic sequelae. The pathophysiology of the post-thrombotic syndrome is
      ambulatory venous hypertension, and patients with valve dysfunction and luminal
      obstruction have the highest ambulatory venous pressures. Treatment designed to
      reduce or eliminate the post-thrombotic syndrome must necessarily remove thrombus
      to eliminate obstruction. The technique of contemporary venous thrombectomy
      follows basic vascular surgical principles and offers patients the opportunity
      for complete or near complete thrombus extraction. The techniques described
      herein represent the authors' approach to patients with few alternatives to clear
      their venous system.

PMID- 22595476
TI  - Reasons why data from the Nationwide Inpatient Sample can be misleading for
      carotid endarterectomy and carotid stenting.
AB  - The Nationwide Inpatient Sample (NIS) is often used for population-based research
      comparing the safety of carotid artery stenting (CAS) to that of carotid
      endarterectomy (CEA) in the United States. At least two findings from the NIS
      dataset seem questionable, however. First, several NIS studies indicate that >90%
      of CEAs and CAS procedures are currently being performed for asymptomatic carotid
      stenosis, which considerably exceeds the prevalence of asymptomatic patients
      reported elsewhere. Second, these studies also suggest that periprocedural stroke
      rates for CEA and CAS are collectively lower at hundreds of community hospitals
      contributing data to the NIS than they were in the Carotid Revascularization
      Endarterectomy Versus Stenting Trial (CREST), even though the participating
      surgeons and interventionalists in CREST were vetted on the basis of their
      previous experience and results. In addition, some unexpectedly low stroke to
      death ratios are present in NIS studies, implying that not all iatrogenic strokes
      have been entered into the NIS dataset. These issues might be related to
      inadequate documentation of preprocedural symptoms and periprocedural strokes in
      the medical records, leading to subsequent coding errors in the hospital
      discharge abstracts from which NIS data are extracted. The clinical limitations
      of the NIS and other administrative datasets have been pointed out in the past,
      but they appear to be particularly relevant to carotid interventions and must be
      recognized.

PMID- 22595477
TI  - Treatment of primary varicose veins has changed with the introduction of new
      techniques.
AB  - New technologies have produced a revolution in primary varicose vein treatments.
      Duplex ultrasound is now used for preoperative diagnosis, postoperative
      surveillance, and during many procedures. Ultrasound has also altered our
      understanding of the pathophysiology of chronic venous disease. Laser and
      radiofrequency saphenous ablations are common. Classic techniques, such as
      sclerotherapy, high ligation, stripping, and phlebectomy, have been improved.
      Magnetic resonance venography, computed tomographic venography, and intravascular
      ultrasound have improved diagnostic capabilities. New strategies like ambulatory
      selective varices ablation under local anesthesia (ASVAL) and conservative
      hemodynamic treatment for chronic venous insufficiency (CHIVA) raise important
      questions about how to manage these patients.

PMID- 22595478
TI  - Can pharmacologic agents slow abdominal aortic aneurysm growth?
AB  - Multiple medical therapies have been proposed to prevent abdominal aortic
      aneurysm expansion. Use of these medications, hormones, vitamins, and dietary
      products is based on their ability to alter the pathophysiology of continued
      aortic wall growth. In this review, the explanation of how these medications can
      achieve suppression of abdominal aortic aneurysm is explained in relation to
      their effect on the various aspects of aortic wall inflammation. Despite the
      large number of animal and observational studies, there remain very few
      randomized clinical trials to support use of any of these agents. However, there
      may be sufficient evidence to suggest that statins, doxycycline, vitamin E,
      cyclooxygenase-2 inhibitors, angiotensin-converting enzyme inhibitors, and
      angiotensin II receptor blockers can prove beneficial in some individuals.

PMID- 22595479
TI  - Endovascular interventions for infrapopliteal arterial disease: an update.
AB  - Surgical revascularization has been the cornerstone of limb salvage for patients
      with critical limb ischemia due to infrapopliteal arterial atherosclerotic
      disease. Endovascular procedures such as balloon angioplasty and stenting are
      gaining popularity for treatment of such patients, although level 1 evidence to
      support the superiority of endovascular treatment over saphenous vein bypass is
      still lacking. A review of the literature from the past 2 years reveals that
      balloon angioplasty of the tibial arteries in patients with critical limb
      ischemia carried a 1-year primary patency rate between 33% and 37%, a secondary
      patency rate of 56% to 63%, and a limb-salvage rate of 75% to 100%. Two
      randomized controlled trials failed to show the superiority of primary
      infrapopliteal stenting over balloon angioplasty alone. One randomized controlled
      trial reported the benefit of drug-eluting stents over bare metal stents. Other
      studies documented good early results after secondary stenting, cryoplasty, and
      using retrograde access for tibial interventions. In conclusion, balloon
      angioplasty or stenting, if angioplasty fails, have emerged as reasonable options
      for limb salvage in patients with critical limb ischemia. More studies are needed
      to evaluate the role of percutaneous transluminal angioplasty as the primary
      modality of choice. There is a real need for a new randomized controlled trial to
      compare tibial angioplasty/stenting with autologous surgical bypass.

PMID- 22595480
TI  - Management of the tense abdomen or difficult abdominal closure after operation
      for ruptured abdominal aortic aneurysms.
AB  - Increased intra-abdominal pressure (IAP) and abdominal compartment syndrome (ACS)
      are important clinical problems after repair of ruptured abdominal aortic
      aneurysms and are reviewed here. IAP >20 mm Hg occurs in approximately 50% of
      patients treated with open abdominal aortic aneurysm repair after rupture, and
      approximately 20% develop organ failure or dysfunction, fulfilling the criteria
      for ACS. Patients selected for endovascular aneurysm repair are often more
      hemodynamically stable, perhaps related to not handling the viscera or more
      favorable anatomy, resulting in less bleeding and, consequently, decreased risk
      of developing ACS. Centers that treat most patients with endovascular aneurysm
      repair tend to have the same proportion of ACS as after open repair. There are no
      randomized data on these aspects. Early nonsurgical therapy can prevent
      development of ACS. Medical therapy includes neuromuscular blockade and the
      combination of positive end-expiratory pressure, albumin, and furosemide. This
      proactive strategy can reduce the number of decompressive laparotomies, an
      important detail because treatment of ACS with open abdomen is a morbid
      procedure. When treatment with an open abdomen is necessary, it is important to
      choose a temporary abdominal closure that maintains sterile conditions during
      often prolonged treatment. In addition, it should prevent lateralization of the
      bowel wall and adhesions between the intestines and the bowel wall.
      Enteroatmospheric fistulae must be prevented. Many alternative methods have been
      suggested, but we prefer the combination of vacuum-assisted wound closure with
      mesh-mediated traction, which will be described.

PMID- 22595481
TI  - Open versus endovascular stent graft repair for abdominal aortic aneurysms: an
      historical view.
AB  - Development of endovascular abdominal aortic aneurysms repair (EVAR), now in its
      4th decade, has involved at least 16 different devices, not counting major
      modifications of some, only 4 of which have emerged from clinical trials and
      gained US Food and Drug Administration approval. The main impetus behind EVAR has
      been its potential for significantly reducing procedural mortality and morbidity,
      but it was also expected to speed recovery and reduce costs through decreased use
      of hospital resources. At the outset, EVAR was touted as a better alternative to
      OPEN in high-risk patients with large abdominal aortic aneurysms, and to
      "watchful waiting" (periodic ultrasound surveillance) for those with small
      abdominal aortic aneurysms. This new technology has evoked a mixed response with
      enthusiasts and detractors debating its pros and cons. Bias and conflict of
      interest exist on both sides. This review will attempt to present a balanced
      review of the development and current status of this controversial competition
      between EVAR and OPEN, comparing them in terms of the following key
      considerations: mortality and morbidity, complications, failure modes and
      durability, and costs.

PMID- 22595482
TI  - Noninvasive evaluation for congenital arteriovenous fistulas and malformations.
AB  - Although relatively rare, congenital arteriovenous fistulas and other vascular
      anomalies present a diagnostic challenge to the clinician. The same noninvasive
      tests that are used for diagnosing arterial occlusive disease in the extremities
      will also detect arteriovenous fistulas. These tests include segmental limb
      pressure measurements, segmental plethysmography, and arterial waveform analysis.
      Additionally, magnetic resonance imaging can be used to determine the extent of
      these vascular anomalies and the involvement of muscle skin and bone, all of
      which have a direct bearing on resectability. This article will examine these
      diagnostic modalities and explain how they can be used in this setting.

PMID- 22595483
TI  - Electrochemical removal of fluoride from water by PAOA-modified carbon felt
      electrodes in a continuous flow reactor.
AB  - A novel poly(aniline-co-o-aminophenol) (PAOA) modified carbon felt electrode
      reactor was designed and investigated for fluoride removal from aqueous
      solutions. This reactor design is innovative because it operates under a wider pH
      range because of coating with a copolymer PAOA ion exchange film. In addition,
      contaminant mass transfer from bulk solution to the electrode surface is enhanced
      by the porous carbon felt as an electron-conducting carrier material compared to
      other reactors. The electrically controlled anion exchange mechanism was
      investigated by X-ray photoelectron spectroscopy and cyclic voltammetry. The
      applicability of the reactor in the field was tested through a series of
      continuous flow experiments. When the flow rate and initial fluoride
      concentration were increased, the breakthrough curve became sharper, which lead
      to a decrease in the breakthrough time and the defluoridation capacity of the
      reactor. The terminal potential values largely influenced fluoride removal by the
      reactor and the optimal defluoridation efficiency was observed at around 1.2V.
      The breakthrough capacities were all >10mg/g over a wide pH range (pH 5-9) with
      an initial fluoride concentration of 10mg/L. Consecutive treatment-regeneration
      studies over a week (once each day) revealed that the PAOA-modified carbon felt
      electrode could be effectively regenerated for reuse. The PAOA-modified carbon
      felt electrode reactor is a promising system that could be made commercially
      available for fluoride removal from aqueous solutions in field applications.

PMID- 22595484
TI  - Discontinuation of antiepileptic drugs after successful epilepsy surgery. a
      Canadian survey.
AB  - INTRODUCTION: To identify the perceived practice among Canadian epileptologists
      regarding discontinuation of antiepileptic drugs (AEDs) following successful
      resective surgery for temporal and extratemporal surgery. METHODS: We performed a
      survey of pediatric and adult epileptologists in Canada, using a 77-item
      questionnaire to explore attitudes, timing, rate of withdrawal, and factors
      contributing to the decision to withdraw AEDs after successful epilepsy surgery.
      Surveys were mailed with a postage-paid return envelope. Two subsequent surveys
      were mailed to non-respondents at 15 days intervals. All procedures received
      institutional review board approval. RESULTS: Surveys were sent to 82
      epileptologists in all the Canadian provinces. Sixty-six physicians answered the
      survey (80.5%), representing all epilepsy centers across Canada. The minimum
      seizure free period required after epilepsy surgery before withdrawing AEDs,
      varied substantially among responders: <6 months in 10%, 6-11 months in 21%, >1
      year in 50%, >2 years in 12%, >2 years in 3% after. The most important factors
      influencing the decision to withdraw AEDs a negative EEG before discontinuation
      (71%), patients' preferences (78%) and the presence of unilateral mesial temporal
      sclerosis (70%). The most important factors against reduction were the following:
      patients' wishes to resume driving (67%), focal (65%) or generalized (78%)
      epileptiform activity on EEG after surgery, persistent isolated auras (78%), any
      seizures after hospital discharge (81%), and presurgical
      multifocal/bilateral/diffuse findings (78%). DISCUSSION: Canadian epileptologists
      indicated that AED levels, EEG and MRI are typically done before discontinuing
      AEDs. Generally, a good candidate for stopping AEDs has focal pathology, is
      completely seizure free, had an anterior temporal lobe resection, complete
      resection of seizure focus, and has no epileptiform discharges on postoperative
      EEG. The data pertaining to self-reported practice styles, and actual practice
      may differ.

PMID- 22595485
TI  - CSF dynamics analysis in patients with post-traumatic ventriculomegaly.
AB  - OBJECTIVE: The management of post-traumatic ventriculomegaly (PTV) is
      controversial. This is due to the difficulty to determine whether PTV is related
      to an atrophic process or to a true "active" hydrocephalus. The purpose of this
      study is to analyze the CSF-dynamics in patients with PTV and, possibly, to
      identify parameters that correlate with prognosis. METHODS: 15 patients with PTV
      were treated following this protocol: 1-frontal ventriculostomy (with Rickham
      reservoir); 2-CSF-dynamics evaluation; 3-ventriculo-peritoneal shunt. CSF
      dynamics evaluation was based on an intraventricular infusion test (performed
      three to five days after ventriculostomy). Outflow Resistance (R-out) and
      Intracranial Elastance Index (EI, i.e. the reciprocal of intracranial compliance)
      were calculated. Patients were classified according to response to shunt into: 1
      fast responders: rapid clinical improvement, i.e. within days/one month from
      surgery; 2-slow responders: patients presenting little clinical improvement
      occurring after months (despite neurorehabilitation); 3-non responders: no
      clinical improvement. RESULTS: Seven patients (46.7%) were classified as fast
      responders, three patients were classified as slow-responders (20%) and five
      patients were classified as non-responders (33.3%). Opening CSF pressure was less
      than 15 mmHg for all patients. R-out (cut-off >10 mmHg/ml/min) had 100%
      sensitivity, 50% specificity, 100% negative predictive value and 63.6% positive
      predictive value. EI (cut-off value >0.3) had 100% specificity, 42.4%
      sensitivity, 100% positive predictive value and 66.7% negative predictive value.
      CONCLUSIONS: Based on these considerations, we can suggest that, for patients
      with normal pressure PTV, analysis of CSF dynamics could be of help in selecting
      patients for CSF-shunt. A combination of Intracranial Elastance and of R-out
      could help predicting shunt responsiveness.

PMID- 22595486
TI  - Elemental micro-imaging and quantification of human substantia nigra using
      synchrotron radiation based x-ray fluorescence--in relation to Parkinson's
      disease.
AB  - Synchrotron radiation based x-ray fluorescence (SRXRF) was applied to the
      quantitative evaluation of elemental changes in substantia nigra pars compacta
      (SNc) in Parkinson's disease (PD) in the framework of a study on the role of
      chemical elements in the pathophysiology of PD. The analysis was carried out for
      dopaminergic nerve cells and extraneuronal spaces. The mass fractions of P, S,
      Cl, K, Ca, Fe, Cu, Zn, Br and Rb were determined. The application of standard
      samples developed especially for the determination of elemental mass fractions in
      thin tissue sections using the SRXRF technique is presented. Two-dimensional maps
      of elemental distribution show that the location of nerve cells in SNc sections
      is precisely visualized by the high levels of most elements. It was found that
      statistically significant differences between control and PD neurons are observed
      for S (p = 0.04), Cl (p = 0.02), Ca (p = 0.08), Fe (p = 0.04) and Zn (p = 0.04).
      The mass fractions of P (p = 0.08), S (p = 0.07), Cl (p = 0.04), Zn (p = 0.08)
      and Rb (p = 0.08) in areas outside the nerve cell bodies differed significantly
      between PD and control groups. A clear cluster separation between the PD nerve
      cells and neurons representing the control group was noticed. It was found that
      Cl, Fe, Ca and Zn are the most significant elements in the general discrimination
      between PD nerve cells and the control. The comparison between the extraneuronal
      spaces showed that Cl, Fe and Cu differentiate the PD and control group the most.
      The evident contribution of chemical elements to the pathophysiology of PD was
      shown.

PMID- 22595487
TI  - Ex vivo and in vivo evaluation of the norepinephrine transporter ligand [11C]MRB
      for brown adipose tissue imaging.
AB  - INTRODUCTION: It has been suggested that brown adipose tissue (BAT) in humans may
      play a role in energy balance and obesity. We conducted ex vivo and in vivo
      evaluation using [(11)C]MRB, a highly selective NET (norepinephrine transporter)
      ligand for BAT imaging at room temperature, which is not achievable with
      [(18)F]FDG. METHODS: PET images of male Sprague-Dawley rats with [(18)F]FDG and
      [(11)C]MRB were compared. Relative [(18)F]FDG or [(11)C]MRB retention at 20, 40
      and 60 min post-injection was quantified on awake rats after exposing to cold (4
      degrees C for 4h) or remaining at room temperature. Rats pretreated with
      unlabeled MRB or nisoxetine 30 min before [(11)C]MRB injection were also
      assessed. The [(11)C]MRB metabolite profile in BAT was evaluated. RESULTS: PET
      imaging demonstrated intense [(11)C]MRB uptake (SUV of 2.9 to 3.3) in the
      interscapular BAT of both room temperature and cold-exposed rats and this uptake
      was significantly diminished by pretreatment with unlabeled MRB; in contrast,
      [(18)F]FDG in BAT was only detected in rats treated with cold. Ex vivo results
      were concordant with the imaging findings; i.e. the uptake of [(11)C]MRB in BAT
      was 3 times higher than that of [(18)F]FDG at room temperature (P=0.009), and the
      significant cold-stimulated uptake in BAT with [(18)F]FDG (10-fold, P=0.001) was
      not observed with [(11)C]MRB (P=0.082). HPLC analysis revealed 94%-99% of total
      radioactivity in BAT represented unchanged [(11)C]MRB. CONCLUSIONS: Our study
      demonstrates that BAT could be specifically labeled with [(11)C]MRB at room
      temperature and under cold conditions, supporting a NET-PET strategy for imaging
      BAT in humans under basal conditions.

PMID- 22595489
TI  - The estimated disease burden of norovirus in The Netherlands.
AB  - Noroviruses are an important cause of acute gastroenteritis in humans. We
      incorporated new insights gained over the past decade in an updated estimate of
      the disease burden of (foodborne) norovirus illness in The Netherlands in 2009.
      The disease outcomes - non-consulting cases, visiting a general practitioner,
      hospitalization and mortality - and the foodborne proportion were derived from
      cohort studies, surveillance data and literature. Age-specific incidence
      estimates were applied to the population age distribution in The Netherlands in
      2009. The general population incidence was 3800/100 000 (95% CI 2670-5460),
      including 0.4 fatal cases/100 000,resulting in 1622 (95% CI 966-2650) disability
      adjusted life-years in a population of 16.5 million [corrected].The updated
      burden of norovirus is over twofold higher than previously estimated, due in
      particular to the new insights in case-fatality ratios. Results suggest that the
      burden of norovirus institutional outbreaks is relatively small compared to the
      burden of community-acquired norovirus infections.

PMID- 22595488
TI  - Prolonged generalized dystonia after chronic cerebellar application of kainic
      acid.
AB  - Dystonia has traditionally been considered as a basal ganglia disorder, but there
      is growing evidence that impaired function of the cerebellum may also play a
      crucial part in the pathogenesis of this disorder. We now demonstrate that
      chronic application of kainic acid into the cerebellar vermis of rats results in
      a prolonged and generalized dystonic motor phenotype and provide detailed
      characterization of this new animal model for dystonia. c-fos expression, as a
      marker of neuronal activation, was increased not only in the cerebellum itself,
      but also in the ventro-anterior thalamus, further supporting the assumption of a
      disturbed neuronal network underlying the pathogenesis of this disorder.
      Preproenkephalin expression in the striatum was reduced, but prodynorphin
      expression remained unaltered, suggesting secondary changes in the indirect, but
      not in the direct basal ganglia pathway in our model system. Hsp70 expression was
      specifically increased in the Purkinje cell layer and the red nucleus. This new
      rat model of dystonia may be useful not only for further studies investigating
      the role of the cerebellum in the pathogenesis of dystonia, but also to assess
      compounds for their beneficial effect on dystonia in a rodent model of prolonged,
      generalized dystonia.

PMID- 22595490
TI  - Characteristics of acute treatment costs of traumatic brain injury in Eastern
      China--a multi-centre prospective observational study.
AB  - INTRODUCTION: This study investigated acute treatment costs and related factors
      for traumatic brain injuries (TBI) in eastern China based on a prospective
      multicentre study. MATERIALS AND METHODS: Data were prospectively collected from
      80 hospitals in eastern China by standardized structured questionnaires during
      2004. Included patients were admitted to hospitals via an emergency service with
      a diagnosis of TBI. The total acute hospitalization treatment costs derived from
      unsubsidized total hospital billings were used as the main outcome measure.
      Univariate and multivariable regression models were used to examine factors
      associated with each outcome. RESULTS: In total, 13,007 TBI cases were identified
      from 80 hospitals in eastern China. The median cost per hospitalization was $879
      US (range, $72-45,894). The median cost per day was $79 (interquartile range, $49
      126). The hospitalization costs varied based on the cause of TBI, with a median
      of $1017 for traffic accidents, $816 for falls, $490 for blows to the head, and
      $712 for falls. The hospitalization costs also varied by injury type with a mean
      of $918 for TBI associated with other injuries and $831 for isolated TBI. Using
      multiple regression analyses, lower admission Glasgow Coma score, longer hospital
      stay (LOS), male sex, transient patient status, traffic accident, injury
      occurring on a construction site, treatment at a tertiary hospital, neurosurgical
      intensive care unit (NICU) or ICU stay, associated polytrauma, and those who
      needed a neurosurgical operation had significantly higher total acute
      hospitalization costs than those of other groups. Good recovery and self-paying
      patients had lower total costs. A double LOS was associated with a 1.61 (95%
      confidence interval, 1.59-1.62) times higher hospital cost. CONCLUSION: Our
      results have potential implications for health-care resource planning during TBI
      treatment. Measures to prevent traffic accidents and reduce the LOS may help to
      reduce acute hospitalization costs.

PMID- 22595491
TI  - Iron status, malaria parasite loads and food policies: evidence from sub-Saharan
      Africa.
AB  - This brief article investigates the consequences of improving children's iron
      status for malaria parasite loads by analyzing data from Cote d'Ivoire, Zambia,
      and Tanzania; the treatment of iron deficiencies has been argued to flare up
      malaria in under-nourished populations. The data from a randomized controlled
      trial in Cote d'Ivoire showed statistically insignificant effects of the
      consumption of iron-fortified biscuits on children's malaria parasite loads.
      Second, nutrient intakes data from Zambia showed insignificant correlations and
      associations between children's iron and folate intakes and malaria parasite
      loads. Third, malaria parasite loads did not change significantly for Tanzanian
      children receiving anthelmintic treatment; malaria loads were lower for older
      children and for those using bed nets. Overall, the evidence from sub-Saharan
      African countries suggests that small improvements in iron status achieved via
      suitable food policies are unlikely to have detrimental effects for children's
      malaria parasite loads.

PMID- 22595492
TI  - Adolescent obesity and life satisfaction: perceptions of self, peers, family, and
      school.
AB  - This study contributes to research on adolescent life satisfaction by considering
      its association with body weight, as mediated by perceptions of self, peers,
      family, and school. Data from the Health Behaviors in School-Age Children Survey
      (2001-2002) and OLS regression techniques are used to examine the association
      between body weight and life satisfaction. We also model these relationships by
      gender. Results indicate lower life satisfaction among adolescents that are
      overweight and obese relative to healthy weight youth, and that most of the
      negative association operates through perceptions of self, peers, parents, and
      school. We find little or no gender difference in the association between body
      weight and perceptions of self, peers, parents, and school; however, we find
      perceptions of body weight are generally more strongly associated with low life
      satisfaction among girls compared to boys.

PMID- 22595493
TI  - Using electrical stimulation to measure physiological changes in the human
      extensor carpi ulnaris muscle after prolonged low-level repetitive ulnar
      deviation.
AB  - The objective of this study was to determine whether muscle fatigue would result
      from repetitive voluntary contractions performed consecutively over four, 8-h
      workdays. Using a repeated measures design, ten healthy females participated in
      three conditions: a control and two repetitive work conditions involving 8 h of
      repeated ulnar deviation of the wrist, at self-selected workloads at 20 and 25
      repetitions per minute (RPM). The 2, 20 and 50 Hz force response of the Extensor
      Carpi Ulnaris muscle was measured before, during work, and in three hours of
      recovery. Twitch contraction times (CT), one-half relaxation times (1/2 RT) and
      20:50 Hz ratios (low frequency fatigue ratios) were also compared. The average
      workloads for the 20 and 25 RPM conditions were 20.3% (+/-11.6%) and 16.3% (+/
      10.8%) MVC respectively. In the exposure conditions there was a decrease in the
      20:50 Hz ratios indicating low frequency fatigue (LFF), a significant increase in
      the muscle's force response across all stimulation frequencies (potentiation),
      and a corresponding decrease (quickening) in the twitch CTs and 1/2 RTs. During
      recovery, the 20:50 Hz ratios, muscle forces and twitch CTs and 1/2 RTs returned
      to pre-exposure/baseline levels. There were no carryover effects or significant
      differences between the two consecutive workdays. For the low-level dynamic
      workloads tested in this study, LFF coexisted with muscle potentiation and the
      results indicated that both LFF ratios and the individual force responses at each
      frequency needs to be evaluated in order to understand the underlying state of
      the muscle.

PMID- 22595495
TI  - Molecular basis of axonal dysfunction and traffic impairments in CMT.
AB  - Charcot-Marie-Tooth disease (CMT) is one of the most common inherited
      neurological disorders. It comprises a group of diseases caused by mutations in
      genes involved in Schwann cells homeostasis and neuronal function that affect the
      peripheral nerves. So far mutations in more than 33 genes have been identified
      causing either the demyelinating form (CMT1) or the axonal form (CMT2). Genes
      involving a large variety of unrelated functions may lead to the same phenotype
      when mutated. Our review will focus on the common link between genes causing
      axonal phenotypes like MFN2, KIF1B, DYNC1H1, Rab7, TRPV4, ARSs, NEFL, HSPB1, MPZ,
      and HSPB8. While KIF1B and DYNC1H1, two genes coding for molecular motors, are
      directly linked to axonal transport, the involvement of the other CMT2-causing
      genes in this function is less obvious. However, the last years have seen a
      growing list of evidence demonstrating that intracellular trafficking and
      mitochondrial dynamics might be dysfunctional in CMT2, and these mechanisms might
      present a common link between dissimilar CMT2-causing genes. The involvement of
      impaired transport in the pathogenesis of other rare neurological diseases or
      recessive CMT2 is also discussed.

PMID- 22595494
TI  - The neurovascular unit and combination treatment strategies for stroke.
AB  - Tissue plasminogen activator (tPA) administered within 4.5h of symptom onset
      restores cerebral blood flow (CBF) and promotes neurological recovery of stroke
      patients. However, the narrow therapeutic time window and the risk of
      intracerebral hemorrhage after tPA treatment pose major hurdles to its clinical
      usage. In light of the failures of neuroprotective therapies in clinical trials,
      emerging concepts suggest that neuroprotection alone without restoration of
      tissue perfusion and vascular integrity may not be adequate for treatment of
      acute stroke. Here we review evidence of the use of adjuvant pharmacological
      agents to extend the therapeutic window for tPA via targeting the neurovascular
      unit and the underlying mechanisms of the combination therapy in experimental
      stroke.

PMID- 22595496
TI  - Evaluation of dose reduction and image quality in chest CT using adaptive
      statistical iterative reconstruction with the same group of patients.
AB  - OBJECTIVES: The objective of this study was to compare the image quality and
      radiation dose of chest CT images reconstructed with a blend of adaptive
      statistical iterative reconstruction (ASIR) and filtered back-projection (FBP)
      with images generated using conventional FBP. METHODS: Patients with chest CT re
      examinations were alternately assigned to two scanners with different
      reconstruction techniques. The study groups included noise index (NI) 11 with 30%
      ASIR (A30), NI 13 with 40% ASIR (A40), NI 15 with 50% ASIR (A50) and NI 17 with
      60% ASIR (A60), sequentially changed every 2 months. The control images were
      obtained using FBP and NI 11. All acquisitions were performed with automatic dose
      modulation. Paired t-test and non-parameter test were applied to compare the
      difference. RESULTS: The radiation doses were significantly lower in the
      examinations that used ASIR (p<0.001). The mean dose reduction rate was 27.7%,
      45.2%, 57.1% and 71.8% for Groups A30, A40, A50 and A60, respectively. The image
      quality of Groups A30-A50 was not inferior to that of the control examinations.
      The image noise of Group A60 was greater and subjective image quality was
      inferior to that of the control. CONCLUSIONS: ASIR enabled the use of a higher NI
      with automatic dose modulation. With 50% ASIR and a NI of 15, the effective
      radiation dose was reduced by 57%, without compromising image quality.

PMID- 22595497
TI  - Establishment of CT diagnostic reference levels in Ireland.
AB  - OBJECTIVE: To propose Irish CT diagnostic reference levels (DRLs) by collecting
      radiation doses for the most commonly performed CT examinations. METHODS: A pilot
      study investigated the most frequent CT examinations. 40 CT sites were then asked
      to complete a survey booklet to allow the recording of CT parameters for each of
      9 CT examinations during a 12-week period. Dose data [CT volume index (CTDI(vol))
      and dose-length product (DLP)] on a minimum of 10 average-sized patients in each
      category were recorded to calculate a mean site CTDI(vol) and DLP value. The
      rounded 75th percentile was used to calculate a DRL for each site and the country
      by compiling all results. RESULTS: are compared with international DRL data.
      Results Data were collected for 3305 patients. 30 sites responded with data for
      34 scanners, representing 54% of the national total. All equipment had multislice
      capability (2-128 slices). DRLs are proposed using CTDI(vol) (mGy) and DLP (mGy
      cm) for CT head (66/58 and 940, respectively), sinuses (16 and 210,
      respectively), cervical spine (19 and 420, respectively), thorax (9/11 and 390,
      respectively), high resolution CT (7 and 280, respectively), CT pulmonary
      angiography (13 and 430, respectively), multiphase abdomen (13 and 1120,
      respectively), routine abdomen/pelvis (12 and 600, respectively) and trunk
      examinations (10/12 and 850, respectively). These values are lower than current
      DRLs and comparable to other international studies. Wide variations in mean doses
      are noted across sites. CONCLUSIONS: Baseline figures for Irish CT DRLs are
      provided on the most frequently performed CT examinations. The variations in dose
      between CT departments as well as between identical scanners suggest a large
      potential for optimisation of examinations.

PMID- 22595498
TI  - 64-detector row CT evaluation of bronchial and non-bronchial systemic arteries in
      life-threatening haemoptysis.
AB  - OBJECTIVE: To retrospectively evaluate the depiction of bronchial and non
      bronchial systemic arteries with 64-detector row CT in patients undergoing
      endovascular treatment for life-threatening haemoptysis. METHODS: 64-detector row
      helical CT and conventional angiography of the thorax were performed in 28
      patients (25 males, 3 females; age range, 18-65 years; mean age, 40 years) with
      life-threatening haemoptysis. CT images were analysed to identify abnormal
      bronchial and non-bronchial systemic arteries and also to localise them in two
      planes. RESULTS: Using multidetector CT (MDCT), 43 bronchial arteries were
      identified on the right side and 46 on the left side. 89% of the right bronchial
      arteries originated from the right intercostobronchial arteries. A common trunk
      of origin of the right and left bronchial artery was noted in 46% of cases. 23
      non-bronchial systemic arteries were noted on the right side and 41 on the left
      side. Pleural thickening >3 mm was confirmed to be a good predictor of non
      bronchial systemic supply. An internal mammary artery diameter of >3 mm and an
      inferior phrenic artery diameter of >2 mm were sensitive indicators for non
      bronchial systemic supply. CONCLUSION: MDCT is a good investigation tool for
      evaluating life-threatening haemoptysis as it confirms the disease process,
      identifies the origin and ostial position of bronchial arteries, detects non
      bronchial systemic arteries and acts as a roadmap for percutaneous transcatheter
      embolisation.

PMID- 22595499
TI  - Vertebral body corner oedema vs gadolinium enhancement as biomarkers of active
      spinal inflammation in ankylosing spondylitis.
AB  - OBJECTIVE: To investigate the relative performance of T(2) weighted short tau
      inversion-recovery (STIR) and fat-suppressed T(1) weighted gadolinium contrast
      enhanced sequences in depicting active inflammatory lesions in ankylosing
      spondylitis (AS). METHODS: Whole-spine MRI was performed on 32 patients with AS,
      who participated in a clinical trial of infliximab treatment, by STIR and
      contrast-enhanced sequences at baseline and after 30 weeks. The AS spine MRI
      activity (ASspiMRI-a) scoring method was used. The images from these two imaging
      techniques were evaluated separately by two independent readers. RESULTS: For the
      pre-treatment lesion status, the intraclass correlation coefficients comparing
      STIR readings and contrast-enhanced readings were 0.69+/-0.23 for Reader 1 and
      0.65+/-0.21 for Reader 2. At baseline, the mean ASspiMRI-a score was 15.4% and
      17.7% higher for contrast-enhanced images than for STIR images for Reader 1 and
      Reader 2, respectively. After infliximab treatment, Reader 1 rated an ASspiMRI-a
      score reduction of 50.8+/-33.6% and 25.3+/-35.3% for STIR images and contrast
      enhanced images, respectively, whereas Reader 2 rated an ASspiMRI-a score
      reduction of 42.4+/-50.4% and 32.9+/-35.6% for STIR images and contrast-enhanced
      images, respectively. CONCLUSION: While both contrast-enhanced and STIR sequences
      showed sensitivity to change over a short period of time after infliximab
      treatment, these two sequences may reflect different disease mechanisms.

PMID- 22595500
TI  - Phenytoin-induced acute orofacial dyskinesia.

PMID- 22595501
TI  - Brain banks. Do our patients know about them?

PMID- 22595502
TI  - Declaration of conflicts of interest.

PMID- 22595503
TI  - CAD: how it works, how to use it, performance.
AB  - Computer-aided diagnosis (CAD) systems are software algorithms designed to assist
      radiologists (or other practitioners) in solving a diagnostic problem by using a
      visual prompt (or "CAD mark") to direct the observer towards potential pathology.
      CT colonography is a recent arrival to CAD, but could represent one of its most
      fruitful applications in the future. In contrast to other organs, where a variety
      of different pathologies are equally represented, significant colorectal
      pathologies other than polyps and cancer are relatively uncommon. As we shall
      see, this simplifies the diagnostic task for artificial intelligence developers
      and also for radiologists who, ultimately, must make the final decision. This
      review aims to present the current state-of-the-art for CAD applied to CT
      colonography. A brief overview of the technical essentials and of the diagnostic
      performance of CAD in isolation, is followed by an explanation of how CAD is used
      in day-to-day practice. The last section will deal with the most controversial
      issues affecting CAD performance in clinical practice, with a focus on the
      interaction between human and artificial intelligence. 

PMID- 22595504
TI  - Predictive role of post-treatment [18F]FDG PET/CT in patients with uterine
      cervical cancer.
AB  - OBJECTIVE: To evaluate the efficacy of post-treatment positron emission
      tomography (PET)/computed tomography (CT) for identification of tumor recurrence,
      and to determine whether [(18)F]fluorodeoxyglucose (FDG) uptake measured as the
      maximum standardized uptake value (SUV(max)) has predictive role regarding
      survival in patients with uterine cervical cancer. METHODS: Medical records from
      276 women with uterine cervical cancer who had post-treatment [(18)F]FDG PET/CT
      performed were retrospectively reviewed. Results of PET/CT scans were compared
      with histological or clinical examination. RESULTS: Ninety-five (34.4%) of the
      276 patients had documented recurrence by either surgical biopsy or clinical and
      imaging follow-up. Median duration from treatment to PET/CT scan was 24 months
      (range, 6-307). The overall sensitivity, specificity, positive predictive value,
      negative predictive value, and accuracy of post-treatment PET/CT were 94.7%,
      87.8%, 80.4%, 97%, and 90.2%, respectively. The PET/CT scan modified both the
      diagnostic or treatment plan in 67 patients (24.3%). Patients were divided into
      two groups according to cut-off SUV(max) established on the basis of ROC analysis
      (<5.25 vs. >=5.25), and there was a significant difference in OS between groups
      (p=0.001). In addition, the 5-year progression-free survival (PFS) and OS rates
      of patients with a negative PET/CT scan for recurrence were significantly better
      than those with a positive PET/CT (98.62% vs. 17.83%, p<0.0001 for PFS, 99.31%
      vs. 85.38%, p=0.0015 for OS). CONCLUSION: Post-treatment PET/CT scan is a
      sensitive and accurate surveillance modality, and provides prognostic information
      in uterine cervical cancer. Furthermore, it may allow individualization of
      patient care.

PMID- 22595505
TI  - Complications of CT colonography: a review.
AB  - Since its inception, one of the main advantages of computed tomography
      colonography (CTC) over colonoscopy has been its assumed superior safety profile.
      However CTC is not without complication and adverse events are well described.
      Although the risks of insufflation, bowel preparation, contrast media and
      radiation dose are very small, they are not insignificant. This review discusses
      the potential hazards and complications associated with the technique, and
      discuss precautions, which may lessen the risk of occurrence. 

PMID- 22595506
TI  - Cortical thickness of the cognitive control network in obesity and successful
      weight loss maintenance: a preliminary MRI study.
AB  - Cortical thickness of the cognitive control network was contrasted between obese
      (OB), successful weight loss maintainers (SWLM), and lean individuals. OB
      individuals had significant thinning, most notably in the anterior cingulate and
      posterior parietal cortices. SWLM individuals exhibited trends towards thicker
      cortex than OB individuals, which may be important in future studies.

PMID- 22595507
TI  - Regional gray matter changes in obsessive-compulsive disorder: relationship to
      clinical characteristics.
AB  - Regional brain volumes were compared between 23 participants with obsessive
      compulsive disorder (OCD) and 36 healthy controls using magnetic resonance
      imaging with voxel-based morphometry. A volumetric decrease in OCD was found in
      the right mediofrontal cortex. An increase was found in the left temporoparietal
      cortex. Volume alterations were related to symptom severity and age of onset.

PMID- 22595509
TI  - One year longitudinal study of the straight gyrus morphometry in first-episode
      schizophrenia-spectrum patients.
AB  - The aim of this study was to use a region-of-interest approach with magnetic
      resonance imaging to examine the volume of the straight gyrus volume change in
      first-episode schizophrenia-spectrum patients compared with healthy subjects over
      a 1-year follow-up period. We did not find a differential pattern of volumetric
      change between the two groups.

PMID- 22595508
TI  - Prefrontal cortical response to emotional faces in individuals with major
      depressive disorder in remission.
AB  - Abnormalities in the response of the orbitofrontal cortex (OFC) and dorsolateral
      prefrontal cortex (DLPFC) to negative emotional stimuli have been reported in
      acutely depressed patients. However, there is a paucity of studies conducted in
      unmedicated individuals with major depressive disorder in remission (rMDD) to
      assess whether these are trait abnormalities. To address this issue, 19
      medication-free rMDD individuals and 20 healthy comparison (HC) participants were
      scanned using functional magnetic resonance imaging while performing an implicit
      emotion processing task in which they labeled the gender of faces depicting
      negative (fearful), positive (happy) and neutral facial expressions. The rMDD and
      HC groups were compared using a region-of-interest approach for two contrasts:
      fear vs. neutral and happy vs. neutral. Relative to HC, rMDD showed reduced
      activation in left OFC and DLPFC to fearful (vs. neutral) faces. Right DLPFC
      activation to fearful (vs. neutral) faces in the rMDD group showed a significant
      positive correlation with duration of euthymia. The findings support deficits in
      left OFC and DLPFC responses to negative emotional stimuli during euthymic
      periods of MDD, which may reflect trait markers of the illness or a 'scar' due to
      previous depression. Recovery may also be associated with compensatory increases
      in right DLPFC functioning.

PMID- 22595510
TI  - Limbic striatal dopamine D2/3 receptor availability is associated with non
      planning impulsivity in healthy adults after exclusion of potential
      dissimulators.
AB  - Positron emission tomography (PET) studies have reported an association between
      reduced striatal dopamine D2/3 receptor availability and higher scores on self
      report measures of trait impulsivity in healthy adults. However, impulsivity is a
      multi-faceted construct, and it is unclear which aspect(s) of impulsivity might
      be driving these associations. The current study aimed to investigate the
      relationship between limbic (ventral) striatal D2/3 receptor availability and
      individual components of impulsivity (attentional, motor and non-planning) using
      the Barratt Impulsiveness Scale (BIS-11) and [(11)C]raclopride PET in 23 healthy
      volunteers. A partial correlational analysis showed a significant association
      between non-planning impulsiveness (lack of forethought or 'futuring') and limbic
      D2/3 receptor availability, which was only apparent after the exclusion of
      potential dissimulators (indexed by high scores on impression management). Our
      findings suggest that non-planning impulsiveness is associated with individual
      variation in limbic striatal D2/3 receptor availability and that different facets
      of impulsivity may have specific neurochemical correlates. Future studies that
      combine D2/3 receptor imaging with behavioral measures of impulsivity are
      required to further elucidate the precise relationship between individual
      components of trait impulsivity and brain dopaminergic function.

PMID- 22595511
TI  - Diallyl trisulfide induces apoptosis and inhibits proliferation of A549 cells in
      vitro and in vivo.
AB  - Lung cancer is the leading cause of cancer-related mortality all over the world.
      In recent years, pulmonary adenocarcinoma has surpassed squamous cell carcinoma
      in frequency and is the predominant form of lung cancer in many countries.
      Epidemiological investigations have shown an inverse relationship between garlic
      (Allium sativum) consumption and death rate from many cancers. Diallyl trisulfide
      (DATS) is one of the garlic-derived compounds (also known as: organosulfer
      compounds, OSC). DATS can induce apoptosis and inhibit the growth of many cancer
      cell lines. Our study demonstrated that the apoptotic incidents induced by DATS
      were a mitochondria-dependent caspase cascade through a significant decrease of
      the anti-apoptotic Bcl-2 that resulted in up-regulation of the ratio of Bax/Bcl-2
      and the activity of caspase-3, -8, and -9. Eventually, DATS induced the apoptosis
      and inhibited the proliferation in a concentration- and time-dependent manner.
      Furthermore, by establishing an animal model of female BALB/c nude mice with A549
      xenografts, we found that oral gavage of DATS significantly retarded growth of
      A549 xenografts in nude mice without causing weight loss or any other side
      effects compared with the control group. All the evidence both in vitro and in
      vivo suggested that DATS could be an ideal anti-cancer drug.

PMID- 22595512
TI  - Overexpression of cotton (Gossypium hirsutum) dirigent1 gene enhances
      lignification that blocks the spread of Verticillium dahliae.
AB  - Dirigent super-family abounds throughout the plant kingdom, especially vascular
      plants. To elucidate the function of cotton (Gossypium hirsutum) DIR genes in
      lignification, two cDNAs (designated GhDIR1 and GhDIR2) encoding putative
      dirigent proteins were isolated from cotton cDNA libraries. Real-time
      quantitative reverse transcription-polymerase chain reaction analysis revealed
      that GhDIR1 transcript was preferentially accumulated in cotton hypocotyls,
      whereas GhDIR2 was predominantly expressed in cotton fibers. Overexpression of
      GhDIR1 gene resulted in an increase in lignin content in transgenic cotton
      plants, compared with that of wild type. Histochemical assay revealed that the
      transgenic plants displayed more widespread lignification than that of wild type
      in epidermis and vascular bundle. Furthermore, the transgenic cotton plants
      displayed more tolerance to the infection of Verticillium dahliae. Our data
      suggest that GhDIR1 may be involved in cotton lignification which can block the
      spread of fungal pathogen V. dahliae.

PMID- 22595513
TI  - Identification and characterization of the zebrafish pharyngeal arch-specific
      enhancer for the basic helix-loop-helix transcription factor Hand2.
AB  - The development of the vertebrate jaw relies on a network of transcription
      factors that patterns the dorsal-ventral axis of the pharyngeal arches. Recent
      findings in both mouse and zebrafish illustrate that the basic-helix-loop-helix
      transcription factor, Hand2, is crucial in this patterning process. While Hand2
      has functionally similar roles in these two species, little is known about the
      regulatory sequences controlling hand2 expression in zebrafish. Using
      bioinformatics and Tol2-mediated transgenesis, we have generated zebrafish
      transgenic reporter lines in which either the mouse or zebrafish arch-specific
      hand2 enhancer direct expression of a fluorescent reporter. We find that both the
      mouse and zebrafish enhancers drive early reporter expression in a hand2-specific
      pattern in the ventral pharyngeal arches of zebrafish embryos. These lines
      provide useful tools to follow ventral arch cells during vertebrate jaw
      development while also allowing dissection of hand2 transcriptional regulation
      during this process.

PMID- 22595515
TI  - The Arf-GEF Schizo/Loner regulates N-cadherin to induce fusion competence of
      Drosophila myoblasts.
AB  - Myoblast fusion is a key process in multinucleated muscle formation. Prior to
      fusion, myoblasts recognize and adhere to each other with the aid of cell
      adhesion proteins integrated into the membrane. Their intracellular domains
      participate in signal transduction by binding to cytoplasmic proteins. Here we
      identified the calcium-dependent cell-adhesion protein N-cadherin as the binding
      partner of the guanine-nucleotide exchange factor Schizo/Loner in Drosophila
      melanogaster. N-cadherin was expressed in founder cells and fusion-competent
      myoblasts of Drosophila during the first fusion phase. Our genetic analyses
      demonstrated that the myoblast fusion defect of schizo/loner mutants is rescued
      in part by the loss-of-function mutation of N-cadherin, which suggests that
      Schizo/Loner is a negative regulator of N-cadherin. Based on our findings, we
      propose a model where N-cadherin must be removed from the myoblast membrane to
      induce a protein-free zone at the cell-cell contact point to permit fusion.

PMID- 22595516
TI  - The pertussis epidemic: informing strategies for prevention of severe disease.
AB  - To assess the impact of Bordetella pertussis infections in South Australia during
      an epidemic and determine vulnerable populations, data from notification reports
      for pertussis cases occurring between July 2008 and December 2009 were reviewed
      to determine the distribution of disease according to specific risk factors and
      examine associations with hospitalizations. Although the majority (66%) of the
      6230 notifications for pertussis occurred in adults aged >24 years, the highest
      notification and hospitalization rate occurred in infants aged <1 year. For these
      infants, factors associated with hospitalization included being aged <2 months
      [relative risk (RR) 2.3, 95% confidence interval (CI) 1.60-3.32], Indigenous
      ethnicity (RR 1.7, 95% CI 1.03-2.83) and receiving fewer than two doses of
      pertussis vaccine (RR 4.1, 95% CI 1.37-12.11). A combination of strategies aimed
      at improving direct protection for newborns, vaccination for the elderly, and
      reducing transmission from close contacts of infants are required for prevention
      of severe pertussis disease.

PMID- 22595514
TI  - Initial deployment of the cardiogenic gene regulatory network in the basal
      chordate, Ciona intestinalis.
AB  - The complex, partially redundant gene regulatory architecture underlying
      vertebrate heart formation has been difficult to characterize. Here, we dissect
      the primary cardiac gene regulatory network in the invertebrate chordate, Ciona
      intestinalis. The Ciona heart progenitor lineage is first specified by Fibroblast
      Growth Factor/Map Kinase (FGF/MapK) activation of the transcription factor Ets1/2
      (Ets). Through microarray analysis of sorted heart progenitor cells, we
      identified the complete set of primary genes upregulated by FGF/Ets shortly after
      heart progenitor emergence. Combinatorial sequence analysis of these co-regulated
      genes generated a hypothetical regulatory code consisting of Ets binding sites
      associated with a specific co-motif, ATTA. Through extensive reporter analysis,
      we confirmed the functional importance of the ATTA co-motif in primary heart
      progenitor gene regulation. We then used the Ets/ATTA combination motif to
      successfully predict a number of additional heart progenitor gene regulatory
      elements, including an intronic element driving expression of the core conserved
      cardiac transcription factor, GATAa. This work significantly advances our
      understanding of the Ciona heart gene network. Furthermore, this work has begun
      to elucidate the precise regulatory architecture underlying the conserved,
      primary role of FGF/Ets in chordate heart lineage specification.

PMID- 22595517
TI  - Current issues in combined modality therapy in locally advanced head and neck
      cancer.
AB  - Curative treatment for patients with locally advanced squamous cell carcinomas of
      the head and neck (SCCHN) is complex and multidisciplinary. Our understanding of
      the optimal management of this disease has improved over the years, incorporating
      refined surgical approaches, better radiotherapy delivery methods, and greater
      use of systemic therapies. Investigation into shifting epidemiology patterns has
      uncovered two biologically and clinically distinct diseases: the smoking-related
      entity and the increasingly common malignancy associated with human papilloma
      virus (HPV). Prognosis favors the latter, driving newer investigations into dose
      de-intensification to limit toxicities in patients with HPV-driven disease, and
      alternatively intensifying treatment to improve tumor control in those with a
      significant smoking history. In this review, I describe the most recent progress
      in the multi-modal integration of radiotherapy and chemoradiotherapy, and the
      role of targeted agents and personalized therapy, and conclude with a discussion
      of the relevance of these innovations with respect to HPV tumor status.

PMID- 22595518
TI  - Determination of CMPO using HPLC-UV.
AB  - Octyl(phenyl)-N,N-diisobutylcarbamoylmethylphosphine oxide (CMPO) is an
      extractant proposed for selective separation of radionuclide metals from used
      nuclear fuel solutions using solvent extraction. Radiolysis reactions can degrade
      CMPO and reduce separation performance and hence methods for measuring the
      concentration of CMPO are needed. A novel high performance liquid chromatography
      (HPLC) method was developed for measuring CMPO in dodecane that featured a low pH
      buffer, octanol as a co-solvent with 2-propanol, and ultraviolet (UV) detection.
      Validation data indicated that the HPLC-UV method for CMPO determination provided
      good linearity, sensitivity, accuracy and precision. Method performance was
      evaluated using CMPO samples that had undergone radiolysis, and the results
      showed a decrease in CMPO concentration and the appearance of degradation
      products. The degradation products were identified using electrospray ionization
      mass spectrometry, which also showed formation of CMPO-nitric acid complexes that
      account for the apparent loss of CMPO in an acidic environment, independent of
      irradiation.

PMID- 22595519
TI  - Isolation of essential oil from different plants and herbs by supercritical fluid
      extraction.
AB  - Supercritical fluid extraction (SFE) is an innovative, clean and environmental
      friendly technology with particular interest for the extraction of essential oil
      from plants and herbs. Supercritical CO(2) is selective, there is no associated
      waste treatment of a toxic solvent, and extraction times are moderate. Further,
      supercritical extracts were often recognized of superior quality when compared
      with those produced by hydro-distillation or liquid-solid extraction. This review
      provides a comprehensive and updated discussion of the developments and
      applications of SFE in the isolation of essential oils from plant matrices. SFE
      is normally performed with pure CO(2) or using a cosolvent; fractionation of the
      extract is commonly accomplished in order to isolate the volatile oil compounds
      from other co-extracted substances. In this review the effect of pressure,
      temperature and cosolvent on the extraction and fractionation procedure is
      discussed. Additionally, a comparison of the extraction yield and composition of
      the essential oil of several plants and herbs from Lamiaceae family, namely
      oregano, sage, thyme, rosemary, basil, marjoram and marigold, which were produced
      in our supercritical pilot-plant device, is presented and discussed.

PMID- 22595520
TI  - Regulation of multiple target genes by miR-1 and miR-206 is pivotal for C2C12
      myoblast differentiation.
AB  - MicroRNAs are short non-coding RNAs involved in post-transcriptional regulation
      of multiple messenger RNA targets. The miR-1/miR-206 family is expressed during
      skeletal muscle differentiation and is an integral component of myogenesis. To
      better understand miR-1/miR-206 function during myoblast differentiation we
      identified novel target mRNAs by microarray and characterized their function in
      C2C12 myoblasts. Candidate targets from the screen were experimentally validated
      together with target genes that were predicted by three different algorithms.
      Some targets characterised have a known function in skeletal muscle development
      and/or differentiation and include Meox2, RARB, Fzd7, MAP4K3, CLCN3 and NFAT5,
      others are potentially novel regulators of myogenesis, such as the chromatin
      remodelling factors Smarcd2 and Smarcb1 or the anti-apoptotic protein SH3BGRL3.
      The expression profiles of confirmed target genes were examined during C2C12 cell
      myogenesis. We found that inhibition of endogenous miR-1 and miR-206 by antimiRs
      blocked the downregulation of most targets in differentiating cells, thus
      indicating that microRNA activity and target interaction is required for muscle
      differentiation. Finally, we show that sustained expression of validated miR-1
      and/or miR-206 targets resulted in increased proliferation and inhibition of
      C2C12 cell myogenesis. In many cases the expression of genes related to non
      muscle cell fates, such as chondrogenesis, was activated. This indicates that the
      concerted downregulation of multiple microRNA targets is not only crucial to the
      skeletal muscle differentiation program but also serves to prevent alternative
      cell fate choices.

PMID- 22595521
TI  - Association of bromodomain BET proteins with chromatin requires dimerization
      through the conserved motif B.
AB  - BET (bromodomain and extra terminal domain) family proteins are unique among
      bromodomain-containing proteins in that they not only associate with acetylated
      chromatin in interphase, but also remain attached to chromosomes during mitosis.
      Although the two tandem bromodomains are essential to display this behaviour,
      they do not suffice. In this work we report that a small conserved domain, motif
      B, is also required. A deletion mutant of this domain dissociates from mitotic
      chromosomes. However, inhibition of histone deacetylases alleviates dissociation.
      We also show that motif-B-dependent association with chromosomes is not
      restricted to mitosis. Interestingly, our results indicate that motif B
      constitutes a surface for homo- and hetero-dimerization between BET proteins.
      Finally, linked to the prominent role BET proteins play in cell proliferation, we
      report that ectopic expression of the family member Brd2 interferes with neuronal
      differentiation in P19 cells and in the vertebrate neural tube, probably because
      of preservation of adequate levels of cyclin A2 and cyclin D1. By contrast, a
      deletion mutant of motif B fails to perform in this way, highlighting the
      relevance of this domain for Brd2 function.

PMID- 22595523
TI  - PEX11 proteins attract Mff and human Fis1 to coordinate peroxisomal fission.
AB  - Fission of membrane-bound organelles requires membrane remodeling processes to
      enable and facilitate the assembly of the scission machinery. Proteins of the
      PEX11 family were shown to act as membrane elongation factors during peroxisome
      proliferation. Furthermore, through interaction with fission factors these
      proteins coordinate progression of membrane scission. Using a biochemical
      approach, we determined the membrane topology of PEX11gamma, one of the three
      human PEX11 proteins. Analysis of PEX11gamma mutants, which localize to
      peroxisomes, revealed essential domains for membrane elongation including an
      amphipathic region and regulatory sequences thereof. Through pegylation assays
      and in vivo studies, we establish that the PEX11gamma sequence includes two
      membrane-anchored domains, which dock an amphipathic region onto the peroxisomal
      membrane thereby regulating its elongation. The interaction profile of wild-type
      and mutant PEX11gamma and reveals a rearrangement between homo- and
      heterodimerization and association with fission factors. We also demonstrate the
      presence of the mitochondrial fission factor Mff on peroxisomes and its
      interaction with PEX11 proteins. Our data reveal several features of the
      molecular mechanism of peroxisome proliferation in mammalian cells: (1)
      PEX11gamma is required and acts in coordination with at least one of the other
      PEX11 proteins to protrude the peroxisomal membrane; (2) PEX11 proteins attract
      both Mff and human Fis1 (hFis1) to their site of action; and (3) the concerted
      interaction of PEX11 proteins provides spatiotemporal control for growth and
      division of peroxisomes.

PMID- 22595524
TI  - The phosphatase of regenerating liver 3 (PRL-3) promotes cell migration through
      Arf-activity-dependent stimulation of integrin alpha5 recycling.
AB  - The formation of metastasis is one of the most critical problems in oncology. The
      phosphatase of regenerating liver 3 (PRL-3) is a new target in colorectal cancer,
      mediating metastatic behavior through a promigratory function. However, detailed
      explanations for this effect have remained elusive. Here we show that PRL-3
      interacts with the ADP-ribosylation factor 1 (Arf1). PRL-3 colocalizes with Arf1
      in an endosomal compartment and associates with transmembrane proteins such as
      the transferrin receptor and alpha5 integrins. PRL-3 interacts with Arf1 through
      a distinct motif and regulates activation of Arf1. PRL-3-mediated migration
      depends on expression and activation of Arf1 and is sensitive to treatment with
      Brefeldin A. We also demonstrate that PRL-3 modulates recycling of alpha5
      integrins and that its phosphatase activity as well as Arf activation and
      compartmentalization with Arf1 are required for this effect. In summary our data
      identify a new function for PRL-3 and show that Arf1 is a new PRL-3-dependent
      mediator of enhanced migration of cancer cells through enhanced recycling of
      matrix receptors.

PMID- 22595522
TI  - Filamin A controls matrix metalloproteinase activity and regulates cell invasion
      in human fibrosarcoma cells.
AB  - Filamins are an important family of actin-binding proteins that, in addition to
      bundling actin filaments, link cell surface adhesion proteins, signaling
      receptors and channels to the actin cytoskeleton, and serve as scaffolds for an
      array of intracellular signaling proteins. Filamins are known to regulate the
      actin cytoskeleton, act as mechanosensors that modulate tissue responses to
      matrix density, control cell motility and inhibit activation of integrin adhesion
      receptors. In this study, we extend the repertoire of filamin activities to
      include control of extracellular matrix (ECM) degradation. We show that knockdown
      of filamin increases matrix metalloproteinase (MMP) activity and induces MMP2
      activation, enhancing the ability of cells to remodel the ECM and increasing
      their invasive potential, without significantly altering two-dimensional random
      cell migration. We further show that within filamin A, the actin-binding domain
      is necessary, but not sufficient, to suppress the ECM degradation seen in filamin
      A-knockdown cells and that dimerization and integrin binding are not required.
      Filamin mutations are associated with neuronal migration disorders and a range of
      congenital malformations characterized by skeletal dysplasia and various
      combinations of cardiac, craniofacial and intestinal anomalies. Furthermore, in
      breast cancers loss of filamin A has been correlated with increased metastatic
      potential. Our data suggest that effects on ECM remodeling and cell invasion
      should be considered when attempting to provide cellular explanations for the
      physiological and pathological effects of altered filamin expression or filamin
      mutations.

PMID- 22595525
TI  - Novel NEDD1 phosphorylation sites regulate gamma-tubulin binding and mitotic
      spindle assembly.
AB  - During cell division, microtubules organize a bipolar spindle to drive accurate
      chromosome segregation to daughter cells. Microtubules are nucleated by the gamma
      TuRC, a gamma-tubulin complex that acts as a template for microtubules with 13
      protofilaments. Cells lacking gamma-TuRC core components do nucleate
      microtubules; however, these polymers fail to form bipolar spindles. NEDD1 is a
      gamma-TuRC-interacting protein whose depletion, although not affecting gamma-TuRC
      stability, causes spindle defects similar to the inhibition of its core subunits,
      including gamma-tubulin. Several residues of NEDD1 are phosphorylated in mitosis.
      However, previously identified phosphorylation sites only partially regulate
      NEDD1 function, as NEDD1 depletion has a much stronger phenotype than mutation of
      these residues. Using mass spectrometry, we have identified multiple novel
      phosphorylated sites in the serine (S)557-S574 region of NEDD1, close to its
      gamma-tubulin-binding domain. Serine to alanine mutations in S565-S574 inhibit
      the binding of NEDD1 to gamma-tubulin and perturb NEDD1 mitotic function,
      yielding microtubule organization defects equivalent to those observed in NEDD1
      depleted cells. Interestingly, additional mutations in the S557-T560 region
      restore the capacity of NEDD1 to bind gamma-tubulin and promote bipolar spindle
      assembly. All together, our data suggest that the NEDD1/gamma-tubulin interaction
      is finely tuned by multiple phosphorylation events in the S557-S574 region and is
      critical for spindle assembly. We also found that CEP192, a centrosomal protein
      similarly required for spindle formation, associates with NEDD1 and modulates its
      mitotic phosphorylation. Thus CEP192 may regulate spindle assembly by modulating
      NEDD1 function.

PMID- 22595527
TI  - Assessment of characteristic distribution of PCDD/Fs and BFRs in sludge generated
      at municipal and industrial wastewater treatment plants.
AB  - The presence of polychlorinated dibenzo-p-dioxins and furan (PCDD/Fs) and
      brominated flame retardants (BFRs) in sludge generated at municipal wastewater
      treatment plants (MWTPs) and industrial wastewater treatment plants (IWTPs) was
      investigated. The concentrations of these pollutants were in the following
      ranges: 5.38-7947ngkg(-1)dw (0.02-49.9ngWHO-TEQkg(-1) dw) for 17 PCDD/Fs, 17.5
      66761MUgkg(-1)dw for 27 polybrominated diphenyl ethers (PBDEs), 1.55-29604MUgkg(
      1)dw for hexabromocyclododecanes (HBCDs) (alpha-, beta-, and gamma
      diastereomers), and 4.01-618MUgkg(-1)dw for tetrabromobisphenol A (TBBPA).
      Generally, the levels of each compound in the sewage-sludge samples were higher
      than those in the industrial-sludge samples with some exceptions. The
      characteristic distribution profiles of target compounds were observed for
      different types of sludge and different sources of wastewater. High-chlorinated
      PCDD/Fs were dominant in all samples except those from the textile industry. The
      distribution of the BFRs in industrial-sludge samples varied, whereas that of the
      BFRs in sewage-sludge samples was consistent. The proportion of penta-BDEs in
      sewage sludge was higher than that in industrial sludge, even though BDE-209 was
      the most dominant congener in all the samples. For HBCDs, the distribution of
      diastereomers (alpha-, beta-, and gamma-HBCD) was similar across sludge samples
      that had the same source of wastewater and treatment processes.

PMID- 22595528
TI  - Reactivity of cycloxydim toward singlet oxygen in solution and on wax film.
AB  - The reactivity of the herbicide cycloxydim (CD) toward singlet oxygen was studied
      in organic solution and on wax films to mimic the leaf surface. Experiments in
      solution were conducted in acetonitrile using phenalenone as a sensitizer. For
      the experiments in the solid state, phenalenone was included in paraffinic wax
      films and CD deposited at the film surface. By laser flash photolysis we observed
      that the triplet of phenalenone reacts with CD with a bimolecular rate constant
      of (9.6 +/- 1) * 10(6)M(-1)s(-1). However, scavenging experiments using beta
      carotene as a singlet oxygen quencher showed that the observed CD degradation in
      aerated acetonitrile involves singlet oxygen essentially. The bimolecular rate
      constant of reaction of CD with singlet oxygen was evaluated to (1.0 +/- 0.2) *
      10(7)M(-1)s(-1). Phenalenone included in the wax films also significantly
      increased the rate of CD photodegradation, the involvement of singlet oxygen
      being very likely. The photoproducts formed via the singlet oxygen pathway
      resulted from the oxidation of the thiol group and/or the cyclohexene ring. This
      study should help to better understand the fate of CD after its spraying on
      crops.

PMID- 22595529
TI  - Using native epiphytic ferns to estimate the atmospheric mercury levels in a
      small-scale gold mining area of West Java, Indonesia.
AB  - Mercury pollution is caused by artisanal and small-scale gold mining (ASGM)
      operations along the Cikaniki River (West Java, Indonesia). The atmosphere is one
      of the primary media through which mercury can disperse. In this study,
      atmospheric mercury levels are estimated using the native epiphytic fern
      Asplenium nidus complex (A. nidus) as a biomonitor; these estimates shed light on
      the atmospheric dispersion of mercury released during mining. Samples were
      collected from 8 sites along the Cikaniki Basin during September-November, 2008
      and September-November, 2009. The A. nidus fronds that were attached to tree
      trunks 1-3m above the ground were collected and measured for total mercury
      concentration using cold vapor atomic absorption spectrometry (CVAAS) after acid
      digestion. The atmospheric mercury was collected using porous gold collectors,
      and the concentrations were determined using double-amalgam CVAAS. The highest
      atmospheric mercury concentration, 1.8 * 10(3) +/- 1.6 * 10(3) ngm(-3), was
      observed at the mining hot spot, and the lowest concentration of mercury, 5.6 +/-
      2.0 ngm(-3), was observed at the remote site from the Cikaniki River in 2009. The
      mercury concentrations in A. nidus were higher at the mining village (5.4 * 10(3)
      +/- 1.6 * 10(3) ngg(-1)) than at the remote site (70 +/- 30 ngg(-1)). The
      distribution of mercury in A. nidus was similar to that in the atmosphere; a
      significant correlation was observed between the mercury concentrations in the
      air and in A. nidus (r=0.895, P<0.001, n=14). The mercury levels in the
      atmosphere can be estimated from the mercury concentration in A. nidus using a
      regression equation: log (Hg(A.nidu)/ngg(-1))=0.740 log (Hg(Air)/ngm (-3)) -
      1.324.

PMID- 22595526
TI  - Microtubule-severing enzymes at the cutting edge.
AB  - ATP-dependent severing of microtubules was first reported in Xenopus laevis egg
      extracts in 1991. Two years later this observation led to the purification of the
      first known microtubule-severing enzyme, katanin. Katanin homologs have now been
      identified throughout the animal kingdom and in plants. Moreover, members of two
      closely related enzyme subfamilies, spastin and fidgetin, have been found to
      sever microtubules and might act alongside katanins in some contexts (Roll-Mecak
      and McNally, 2010; Yu et al., 2008; Zhang et al., 2007). Over the past few years,
      it has become clear that microtubule-severing enzymes contribute to a wide range
      of cellular activities including mitosis and meiosis, morphogenesis, cilia
      biogenesis and disassembly, and migration. Thus, this group of enzymes is
      revealing itself to be among the most important of the microtubule regulators.
      This Commentary focuses on our growing understanding of how microtubule-severing
      enzymes contribute to the organization and dynamics of diverse microtubule
      arrays, as well as the structural and biophysical characteristics that afford
      them the unique capacity to catalyze the removal of tubulin from the interior
      microtubule lattice. Our goal is to provide a broader perspective, focusing on a
      limited number of particularly informative, representative and/or timely
      findings.

PMID- 22595530
TI  - Ecotoxicological effects on earthworms of fresh and aged nano-sized zero-valent
      iron (nZVI) in soil.
AB  - Although nano-sized zero-valent iron (nZVI) has been used for several years for
      remediation of contaminated soils and aquifers, only a limited number of studies
      have investigated secondary environmental effects and ecotoxicity of nZVI to soil
      organisms. In this study we therefore measured the ecotoxicological effects of
      nZVI coated with carboxymethyl cellulose on two species of earthworms, Eisenia
      fetida and Lumbricus rubellus, using standard OECD methods with sandy loam and
      artificial OECD soil. Earthworms were exposed to nZVI concentrations ranging from
      0 to 2000 mg nZVI kg soil(-1) added freshly to soil or aged in non-saturated soil
      for 30 d prior to exposure. Regarding avoidance, weight changes and mortality,
      both earthworm species were significantly affected by nZVI concentrations >=500
      mg kg(-1)soil. Reproduction was affected also at 100 mg nZVI kg(-1). Toxicity
      effects of nZVI were reduced after aging with larger differences between soils
      compared to non-aged soils. We conclude that doses >=500 mg nZVI kg(-1) are
      likely to give acute adverse effects on soil organisms, and that effects on
      reproduction may occur at significantly lower concentrations.

PMID- 22595531
TI  - Toxicological effect of MPA-CdSe QDs exposure on zebrafish embryo and larvae.
AB  - Cadmium selenium (CdSe) quantum dots (QDs) are semiconductor nanocrystals that
      hold wide range of applications and substantial production volumes. Due to unique
      composition and nanoscale properties, their potential toxicity to aquatic
      organisms has increasingly gained a great amount of interest. However, the impact
      of CdSe QDs exposure on zebrafish embryo and larvae remains almost unknown.
      Therefore, the lab study was performed to determine the developmental and
      behavioral toxicities to zebrafish under continuous exposure to low level CdSe
      QDs (0.05-31.25 mg L(-1)) coated with mercaptopropionic acid (MPA). The results
      showed MPA-CdSe exposure from embryo to larvae stage affected overall fitness.
      Our findings for the first time revealed that: (1) The 120 h LC(50) of MPA-CdSe
      for zebrafish was 1.98 mg L(-1); (2) embryos exposed to MPA-CdSe resulted in
      malformations incidence and lower hatch rate; (3) abnormal vascular of FLI-1
      transgenic zebrafish larvae appeared after exposure to MPA-CdSe including
      vascular junction, bifurcation, crossing and particle appearance; (4) larvae
      behavior assessment showed during MPA-CdSe exposure a rapid transition from light
      to-dark elicited a similar, brief burst and a higher basal swimming rate; (5) MPA
      CdSe induced embryos cell apoptosis in the head and tail region. Results of the
      observations provide a basic understanding of MPA-CdSe toxicity to aquatic
      organisms and suggest the need for additional research to identify the
      toxicological mechanism.

PMID- 22595532
TI  - Determining germinal centre B cell fate.
AB  - The humoral immune system generates immunological memory comprising affinity
      matured, long-lived memory B cells and plasma cells (PCs), which are generated
      primarily in germinal centres (GCs). Although many factors are essential in this
      process, those that specifically govern B cell fate are not fully understood. The
      provision of T cell help to B cells is key in GC B cell fate determination, and
      it has become clear recently that this help involves more than direct cell-cell
      interactions. Recently, the cytokine interleukin (IL)-21 has been identified as a
      key factor that can modulate the processes within GCs and directly influence B
      cell fate. In this review, we examine the roles of GC cytokines in the context of
      cell differentiation.

PMID- 22595533
TI  - Explaining the length threshold of polyglutamine aggregation.
AB  - The existence of a length threshold, of about 35 residues, above which
      polyglutamine repeats can give rise to aggregation and to pathologies, is one of
      the hallmarks of polyglutamine neurodegenerative diseases such as Huntington's
      disease. The reason why such a minimal length exists at all has remained one of
      the main open issues in research on the molecular origins of such classes of
      diseases. Following the seminal proposals of Perutz, most research has focused on
      the hunt for a special structure, attainable only above the minimal length, able
      to trigger aggregation. Such a structure has remained elusive and there is
      growing evidence that it might not exist at all. Here we review some basic
      polymer and statistical physics facts and show that the existence of a threshold
      is compatible with the modulation that the repeat length imposes on the
      association and dissociation rates of polyglutamine polypeptides to and from
      oligomers. In particular, their dramatically different functional dependence on
      the length rationalizes the very presence of a threshold and hints at the
      cellular processes that might be at play, in vivo, to prevent aggregation and the
      consequent onset of the disease.

PMID- 22595534
TI  - [Iron metabolism: State of the art].
AB  - About 60% of body iron is associated with hemoglobin in circulating red blood
      cells and daily erythropoiesis requires about 25 to 30mg iron per day. This iron
      is provided by macrophages through recycling of heme iron following phagocytosis
      of senescent red blood cells and heme catabolism. Intestinal iron absorption (1
      to 2mg per day) only compensates for daily iron losses. Hepcidin, a 25 amino-acid
      peptide synthesized in hepatocytes, secreted in plasma and rapidly removed in
      urines, is a negative regulator of both intestinal iron absorption and heme iron
      recycling by macrophages. Hepcidin synthesis is stimulated by iron or by
      inflammation (mostly by IL-6) and is repressed by iron deficiency and by all
      conditions that stimulate bone marrow erythropoiesis such as anemia, bleeding,
      hemolysis, dyserythropoiesis or erythropoietin injections. A defect in the
      activation of hepcidin normally triggered by iron excess is the underlying
      mechanism for all juvenile or adult forms of hemochromatosis whereas a defect in
      hepcidin repression is responsible for an iron deficiency iron refractory anemia
      (IRIDA). Reduced hepcidin filtration in renal insufficiency contributes to the
      associated anemia and stimulation of hepcidin synthesis by inflammation is a
      major determinant of the anemia of chronic disorders. New therapeutic
      perspectives are currently underway such as the development of agonists or
      antagonists of hepcidin or siRNA approaches aiming at reducing hepcidin
      synthesis. The validation of hepcidin assays in a near future will allow
      identifying the patients most likely to benefit from intravenous iron therapy.

PMID- 22595535
TI  - Atypical de Quervain's thyroiditis masquerading as papillary thyroid cancer.

PMID- 22595536
TI  - [Progressive thyroid lymphocytic infiltration in a patient with chronic
      hepatitis].

PMID- 22595537
TI  - Contribution of mitochondria to pain in diabetic neuropathy.
AB  - Diabetes is a metabolic disease affecting approximately 300 million people
      worldwide. Neuropathy is one of its frequent complications, and may affect
      sensory, motor, and autonomic nerves. Its pathophysiology has not fully been
      elucidated. Several hypotheses have been proposed, and mitochondria have been
      suggested to play a significant role. This article reviews the mechanisms
      involved in mitochondrial dysfunction and development of diabetic neuropathy,
      consisting mainly of oxidative and inflammatory stress, changes in intracellular
      calcium regulation, apoptotic processes, and changes in mitochondrial structure
      and function that may lead to development of diabetic neuropathy.

PMID- 22595538
TI  - Molluscicidal activity of Aglaia duperreana and the constituents of its twigs and
      leaves.
AB  - The methanol (MeOH) extract of the twigs and leaves of Aglaia duperreana was
      investigated for its molluscicidal activity against Pomacea canaliculata. The
      extract was found to exhibit significant molluscicidal activity. The ethyl
      acetate soluble fraction of the extract showed the most potent molluscicidal
      activity among different solvent fractions. The bioactivity-guided chemical
      investigation of the ethyl acetate soluble fraction led to a new triterpenoid
      along with 15 known compounds. Their structures were elucidated by spectroscopic
      methods, including one- and two-dimensional nuclear magnetic resonance techniques
      as well as mass spectroscopic analysis. The molluscicidal activities of compounds
      2-16 against P. canaliculata were also investigated. Naringenin trimethyl ether
      showed significant molluscicidal activity with a median lethal concentration
      (LC(50)) of 3.9 MUg/mL, which was indicated higher potency than the positive
      control, tea saponin (LC(50)=4.5 MUg/mL).

PMID- 22595539
TI  - Ultrasound-assisted one-pot synthesis of anti-CML nucleosides featuring 1,2,3
      triazole nucleobase under iron-copper catalysis.
AB  - A simple and efficient synthesis of modified 1,2,3-triazole nucleosides was
      developed. The strategy involved sequential one-pot acetylation-azidation
      cycloaddition procedure and was found to be highly effective under a cooperative
      effect of ultrasound activation and iron/copper catalysis. The reactions were
      carried out under both conventional and ultrasonic irradiation conditions. In
      general, improvement in rates and yields were observed when reactions were
      carried out under sonication compared with conventional conditions. This one-pot
      procedure provides several advantages such as operational simplicity, high yield,
      safety and environment friendly protocol. The resulting substituted nucleosides
      were evaluated for their anticancer activity against K562 chronic myelogenous
      leukemia (CML) cell line.

PMID- 22595540
TI  - Correlation of increased hippocampal Sumo3 with spatial learning ability in old
      C57BL/6 mice.
AB  - Age-related impairment of learning and memory is a common phenomenon in humans
      and animals, yet the underlying mechanism remains unclear. We hypothesize that a
      small ubiquitin-related modifier (Sumo) might correlate with age-related loss of
      learning and memory. To test this hypothesis, the present study evaluated age
      related spatial learning and memory in C57BL/6 mice (25 aged 7 months and 21 aged
      25 months) using a radial six-arm water maze (RAWM). After the behavioral test,
      the protein expression of Sumo3 was determined in different brain regions using
      Western blotting. The results showed that the 25-month-old mice had longer
      latency and a higher number of errors in both learning and memory phases in the
      RAWM task than the 7-month-old mice. Compared to the latter, the former's level
      of Sumo3 protein was significantly increased in the dorsal and ventral
      hippocampus. For the 25-month-old mice, the number of errors and the latency in
      the learning phase negatively correlated with the Sumo3 level in the dorsal
      hippocampus. These results suggest that increased Sumo3 in the hippocampus may be
      correlated with spatial learning ability in old C57BL/6 mice.

PMID- 22595541
TI  - TiO2 nanoparticles suppress Escherichia coli cell division in the absence of UV
      irradiation in acidic conditions.
AB  - TiO(2) nanoparticles (NPs) activated by UV irradiation are known to have a
      bactericidal effect. In this study we report the details of TiO(2) NPs influence
      on the colony-forming capacity of E. coli in the dark at pH 4.0-4.5. At this pH
      the bacterial cells are negatively charged and TiO(2) NPs present a positive
      charge. A 60 min contact between E. coli with TiO(2) at concentrations of 0.02
      0.2 mg/mL led to a reduction of E. coli cell number from 10(8) to 10(4)CFU/mL.
      After the reduction the system remains unchanged during the subsequent
      incubation. The observed reduction was a function on the initial E. coli
      concentration. In the presence of 0.04 mg/mL TiO(2) the colony-forming units
      (CFU) reduction after 60 min was of four-five orders of magnitude when the
      initial concentration was 10(8) cells/mL. But when starting with an E. coli
      concentration of 10(7) cells/mL the cell number reduction was less than one order
      of magnitude. Less than one order of magnitude cell number reduction was also
      observed for suspensions of E. coli 10(8) cells/mL and 0.002 mg/mL of TiO(2). The
      bacteria number reduction was always accompanied by the formation of cell
      aggregates. During cell incubation with TiO(2), the pH of the suspension
      increased, but did not reach the TiO(2) isoelectric point (IEP). E. coli cells
      stained with the fluorescent dye acridine orange (AO) showed that the
      fluorescence of single cells remained unchanged after incubation in the presence
      of TiO(2). The color change of fluorescence was revealed only in aggregated
      cells. This suggests changes in the physiologic state of E. coli incorporated
      into the aggregates. Aggregates of E. coli occur due to the electrostatic
      interaction between TiO(2) NPs and the bacterial cell surface. A hypothesis is
      suggested in this study to explain the CFU reduction and the retention of a
      certain irreducible number of cells capable of further division in the suspension
      in the presence of TiO(2) in the dark.

PMID- 22595542
TI  - Aminopropyl-modified mesoporous silica SBA-15 as recovery agents of Cu(II)
      sulfate solutions: Adsorption efficiency, functional stability and reusability
      aspects.
AB  - Hybrid mesoporous materials are potentially useful for metal ion scavenging and
      retrieval because of their high surface areas, controlled accessibility and
      tailored functionalization. Some aspects that are linked to the performance of
      HMM include pore accessibility, stability of the organic functions and
      reusability. Knowledge of these aspects is critical in the design of adsorption
      desorption protocols. In this work we produce and characterize propylamino
      substituted large pore silica (SBA-15-N), which is submitted to Cu(II) adsorption
      from copper sulfate solutions, followed by desorption in acid media and material
      regeneration. We find that the hybrid material is an efficient adsorbent (1.15
      1.75mmol Cu(II)g(-1)), although a fraction of the organic groups is lost during
      the adsorption process. An X-ray photoelectron spectroscopy (XPS) study
      demonstrates that the contents of amino groups are higher in the material
      surface, leading to different behaviors in Cu(II) complexation along the
      material. These materials can be regenerated by exposure to acidic media. Thermal
      processing of the hybrid materials leads to better durability in aqueous
      solutions during reprocessing, due to enhanced polycondensation of the inorganic
      framework. Thermally treated samples, once regenerated, are efficient adsorbents
      in a second step of Cu(II) adsorption. We discuss the materials processing
      factors involved in the improved adsorption of Cu(II), its quantitative release
      and reusability of the material.

PMID- 22595543
TI  - The use of a halophytic plant species and organic amendments for the remediation
      of a trace elements-contaminated soil under semi-arid conditions.
AB  - The halophytic shrub Atriplex halimus L. was used in a field phytoremediation
      experiment in a semi-arid area highly contaminated by trace elements (As, Cd, Cu,
      Mn, Pb and Zn) within the Sierra Minera of La Union-Cartagena (SE Spain). The
      effects of compost and pig slurry on soil conditions and plant growth were
      determined. The amendments (particularly compost) only slightly affected trace
      element concentrations in soil pore water or their availability to the plants,
      increased soil nutrient and organic matter levels and favoured the development of
      a sustainable soil microbial biomass (effects that were enhanced by the presence
      of A. halimus) as well as, especially for slurry, increasing A. halimus biomass
      and ground cover. With regard to the minimisation of trace elements
      concentrations in the above-ground plant parts, the effectiveness of both
      amendments was greatest 12-16 months after their incorporation. The findings
      demonstrate the potential of A. halimus, particularly in combination with an
      organic amendment, for the challenging task of the phytostabilisation of
      contaminated soils in (semi-)arid areas and suggest the need for an
      ecotoxicological evaluation of the remediated soils. However, the ability of A.
      halimus to accumulate Zn and Cd in the shoot may limit its use to moderately
      contaminated sites.

PMID- 22595544
TI  - Radiolytic formation of non-toxic Cr(III) from toxic Cr(VI) in formate containing
      aqueous solutions: A system for water treatment.
AB  - Toxic hexavalent chromium Cr(VI) in the form of potassium dichromate was
      radiolytically reduced to non-toxic trivalent chromium Cr(III) in N(2)O-saturated
      aqueous solutions containing formate. This reduction by the electron donor
      (CO(2)H/CO(2)(-)) produced by continuous radiolysis of water, was a linear
      function of the absorbed dose. This reaction was pH and dose rate dependent. pH
      was an important parameter in the reduction, as it affects both chemical
      speciation of Cr(VI) and formate. Possible mechanisms related to dose rate
      dependence of removal of Cr(VI) are presented. At pH 3 a decrease in the
      radiation induced reduction of Cr(VI) was observed with increasing hydrogen
      peroxide concentration. A mechanism to account for this variation is proposed.
      These findings suggest that irradiation of Cr(VI) solutions in presence of
      formate can be effective, economical and simple means for treatment of waste
      water contaminated with hexavalent Cr(VI).

PMID- 22595545
TI  - Particulate matter characterization by gray level co-occurrence matrix based
      support vector machines.
AB  - An efficient and highly reliable automatic selection of optimal segmentation
      algorithm for characterizing particulate matter is presented in this paper.
      Support vector machines (SVMs) are used as a new self-regulating classifier
      trained by gray level co-occurrence matrix (GLCM) of the image. This matrix is
      calculated at various angles and the texture features are evaluated for
      classifying the images. Results show that the performance of GLCM-based SVMs is
      drastically improved over the previous histogram-based SVMs. Our proposed GLCM
      based approach of training SVM predicts a robust and more accurate segmentation
      algorithm than the standard histogram technique, as additional information based
      on the spatial relationship between pixels is incorporated for image
      classification. Further, the GLCM-based SVM classifiers were more accurate and
      required less training data when compared to the artificial neural network (ANN)
      classifiers.

PMID- 22595546
TI  - Economic analysis in patient safety: a neglected necessity.

PMID- 22595547
TI  - Vertebral augmentation in the treatment of vertebral compression fractures:
      review and new insights from recent studies.
AB  - Vertebral compression fractures (VCF) due to osteoporotic degeneration and
      metastatic disease represent an increasingly significant public health problem.
      Percutaneous vertebroplasty (VP) began as a simple, low-cost procedure that aimed
      to provide pain relief for patients with VCF. Balloon kyphoplasty (KP) was
      introduced later, and was presented not only as a "pain killer," but also as a
      deformity correction procedure. The preponderance of evidence has shown that
      vertebral augmentation provides significant and sustained clinical benefit for
      patients with VCF. The debate raised by studies published in the New England
      Journal of Medicine comparing VP with a sham procedure highlights the importance
      of very careful patient selection for vertebral augmentation procedures, since
      osteoporotic VCF is usually a self-limiting condition. However, vertebral
      augmentation may be beneficial in patients with comorbidities that make prolonged
      bed rest dangerous, in patients with fractures that fail to heal, and in patients
      with painful VCF due to metastatic disease. Patient selection should be based on
      a combination of clinical and radiological indications. We review recent studies
      in the extensive literature on vertebral augmentation, with the goal of
      clarifying some of the controversy surrounding these procedures.

PMID- 22595548
TI  - Initial characterization of an autoclaved Toxoplasma vaccine in mice.
AB  - Toxoplasmosis is a zoonotic protozoal disease that has a major significance from
      the perspectives of public health and veterinary medicine. Therefore, an obvious
      long-term goal of many scientists would be the development of an effective
      vaccine. In this study, autoclaved vaccine was evaluated for its ability to
      protect mice against Toxoplasma gondii RH challenge as an acute infection model.
      Results showed that autoclaved Toxoplasma vaccine (ATV) when combined with BCG as
      an adjuvant was effective in triggering cell mediated immunity as shown by a
      significant increase in the percentage of splenic CD8+ T-lymphocytes. Following
      challenge, death of mice vaccinated with ATV was delayed for nine days. There was
      a significant decrease in parasite density in different organs, and a marked
      reduction of pathological changes in the liver suggesting that significant immune
      responses were mounted following vaccination. Future studies are warranted to
      test the vaccine against challenge with brain cysts as a chronic infection model
      and to evaluate it with other recent immunization strategies that can further
      enhance its immunogenicity.

PMID- 22595549
TI  - Hepatitis C prevalence in injecting drug users in Europe, 1990-2007: impact of
      study recruitment setting.
AB  - Monitoring injecting drug users' (IDUs) health is challenging because IDUs form a
      difficult to reach population. We examined the impact of recruitment setting on
      hepatitis C prevalence. Individual datasets from 12 studies were merged.
      Predictors of HCV positivity were sought through a multilevel analysis using a
      mixed-effects logistic model, with study identifier as random intercept. HCV
      prevalence ranged from 21% to 86% across the studies. Overall, HCV prevalence was
      higher in IDUs recruited in drug treatment centres compared to those recruited in
      low-threshold settings (74% and 42%, respectively, P < 0.001). Recruitment
      setting remained significantly associated with HCV prevalence after adjustment
      for duration of injecting and recent injection (adjusted odds ratio 0.7, 95%
      confidence interval 0.6-0.8, P = 0.05). Recruitment setting may have an impact on
      HCV prevalence estimates of IDUs in Europe. Assessing the impact of mixed
      recruitment strategies, including respondent-driven sampling, on HCV prevalence
      estimates, would be valuable.

PMID- 22595551
TI  - Pioneer in pediatric psychology: echoing the voices of children: a journey
      through pediatric psychology.

PMID- 22595550
TI  - Estrogen and the skeleton.
AB  - Estrogen is the major hormonal regulator of bone metabolism in women and men.
      Therefore, there is considerable interest in unraveling the pathways by which
      estrogen exerts its protective effects on bone. Although the major consequence of
      the loss of estrogen is an increase in bone resorption, estrogen deficiency is
      associated with a gap between bone resorption and formation, indicating that
      estrogen is also important for maintaining bone formation at the cellular level.
      Direct estrogen effects on osteocytes, osteoclasts, and osteoblasts lead to
      inhibition of bone remodeling, decreased bone resorption, and maintenance of bone
      formation, respectively. Estrogen also modulates osteoblast/osteocyte and T-cell
      regulation of osteoclasts. Unraveling these pleiotropic effects of estrogen may
      lead to new approaches to prevent and treat osteoporosis.

PMID- 22595552
TI  - Efficient production of ultrapure manganese oxides via electrodeposition.
AB  - A new process for the production of electrolytic amorphous nanomanganese oxides
      (EAMD) with uniform size and morphology is described. EAMD are produced for the
      first time by cathodic deposition from a basic aqueous solution of potassium
      permanganate at a constant temperature of 16 degrees C. The synthesized materials
      are characterized by XRD, SEM, TEM, and HRTEM. The materials produced at 5.0 V at
      constant temperature are amorphous with homogeneous size and morphology with an
      average particle size around 20 nm, which appears to be much lesser than the
      previously reported anodic EAMD. A potentiostatic electrodeposition with much
      lesser deposition rate (with respect to previously reported anodic depositions)
      is considered to be the reason behind the very low and homogenous particle size
      distribution due to the lesser agglomeration of our as-synthesized nanoparticles.

PMID- 22595553
TI  - Estimating the health benefits from natural gas use in transport and heating in
      Santiago, Chile.
AB  - Chilean law requires the assessment of air pollution control strategies for their
      costs and benefits. Here we employ an online weather and chemical transport
      model, WRF-Chem, and a gridded population density map, LANDSCAN, to estimate
      changes in fine particle pollution exposure, health benefits, and economic
      valuation for two emission reduction strategies based on increasing the use of
      compressed natural gas (CNG) in Santiago, Chile. The first scenario, switching to
      a CNG public transportation system, would reduce urban PM2.5 emissions by 229
      t/year. The second scenario would reduce wood burning emissions by 671 t/year,
      with unique hourly emission reductions distributed from daily heating demand. The
      CNG bus scenario reduces annual PM2.5 by 0.33 MUg/m3 and up to 2 MUg/m3 during
      winter months, while the residential heating scenario reduces annual PM2.5 by
      2.07 MUg/m3, with peaks exceeding 8 MUg/m3 during strong air pollution episodes
      in winter months. These ambient pollution reductions lead to 36 avoided premature
      mortalities for the CNG bus scenario, and 229 for the CNG heating scenario. Both
      policies are shown to be cost-effective ways of reducing air pollution, as they
      target high-emitting area pollution sources and reduce concentrations over
      densely populated urban areas as well as less dense areas outside the city
      limits. Unlike the concentration rollback methods commonly used in public policy
      analyses, which assume homogeneous reductions across a whole city (including
      homogeneous population densities), and without accounting for the seasonality of
      certain emissions, this approach accounts for both seasonality and diurnal
      emission profiles for both the transportation and residential heating sectors.

PMID- 22595554
TI  - Seasonal variations, speciation and possible sources of mercury in the snowpack
      of Zhadang glacier, Mt. Nyainqentanglha, southern Tibetan Plateau.
AB  - Ten snowpits were sampled at the Zhadang glacier during 2008 and 2011 to
      investigate the seasonal variations, speciation, and sources of mercury (Hg) in
      the southern Tibetan Plateau. In the 2008 snowpit, total Hg (Hg(T)), particulate
      matter, most of major ions were found in higher concentrations during the non
      monsoon season than in the monsoon season. Analysis of Hg speciation indicated
      that Hg(T) in the 2011 snowpits was dominated by particulate-bound Hg (Hg(P)).
      Most of particulate matter in the 2008 snowpit was dominated by fine
      particulates, indicating that the influx of particulate matter and Hg(P) was
      probably occurring by long-range transportation via general atmospheric
      circulation. Analysis of dominant ion Ca2+ and alkaline pH values has suggested
      that the long-range transported Hg(P), originating from dust storm activities,
      may be the most important source for Hg in the Zhadang glacier snowpit during the
      non-monsoon season. Backward-trajectory analysis indicates the majority of the
      air masses arriving at the Zhandang glacier originated from the arid regions of
      northwestern India (e.g., Thar Desert), confirming that arid regions in central
      and southern Asia are likely the main sources of Hg being deposited in the
      Zhadang glacier snowpit. This study also suggests that ice core records from the
      Tibetan Plateau may be useful tools for interpreting long-term historical records
      of atmospheric Hg deposition, and reconstructing Hg biogeochemical cycling.

PMID- 22595555
TI  - Improved debromination of polybrominated diphenyl ethers by bimetallic iron
      silver nanoparticles coupled with microwave energy.
AB  - This study focused on the enhanced debromination of decabromodiphenyl ether (BDE
      209) and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) by Fe-Ag nano-particles
      under microwave radiation (Fe-Ag/MW). Fe-Ag bimetallic nano-particles were
      synthesized by reductive deposition of Ag on nano-iron and characterized with a
      number of techniques, including BET, XRD, TEM and XPS. Approximately 97% of BDE
      209 or 78% of BDE-47 were rapidly transformed to its degradation products within
      8 min in the Fe-Ag/MW system. The dehalogenation efficiency of polybrominated
      diphenyl ethers (PBDEs) was enhanced apparently by microwave radiation. Moreover,
      the microwave thermal energy played a significant role in accelerating the
      degradation reactions. Compared with nano-iron alone, the deposition of Ag also
      increased the rates of degradation. GC-MS and LC-MS/MS analyses of PBDEs'
      degradation products reveals that the possible degradation pathway proceeds
      through stepwise debromination from [n]-bromo- to [n-1]-bromo-DE, with bromine
      being substituted by hydrogen sequentially. Di- to nona-brominated congeners were
      formed during BDE-209 reduction, while diphenyl ether to tri-BDEs were observed
      during BDE-47 degradation. These results suggest that PBDEs can be debrominated
      rapidly by the innovative processes that may be environmentally friendly in
      applications.

PMID- 22595556
TI  - International innovations in pediatric minimally invasive surgery: the Argentine
      experience.
AB  - This is a presentation about innovations in pediatric minimally invasive surgery
      and a review of the Argentine experience. The most representative are (1) the
      thoracoscopic treatment of long gap esophageal atresia with novel techniques; (2)
      the nonsurgical and minimally invasive treatment of chest wall deformities,
      particularly of pectus carinatum; and (3) the use of magnetic surgical devices in
      classic laparoscopy and transumbilical surgery.

PMID- 22595557
TI  - Multi-institutional follow-up of patients with congenital diaphragmatic hernia
      reveals severe disability and variations in practice.
AB  - BACKGROUND/PURPOSE: Survivors of congenital diaphragmatic hernia (CDH) have a
      high incidence of morbidity. Variability in follow-up practices between
      institutions may affect perception of disability and prevent population-based
      outcome analysis. METHODS: A survey of follow-up practices at 16 centers within a
      population-based CDH network was performed. A descriptive analysis of outcomes
      (minimum 24 months postdischarge) of CDH survivors from the 2 largest centers was
      performed. RESULTS: The nature of follow-up of CDH survivors was highly variable
      in 12 of 16 responding centers, ranging from ad hoc, community-based, and
      pediatrician-sponsored follow-up to a single perinatal center-based
      multispecialty CDH clinic. Outcomes at 24 to 36 months were reported from the 2
      largest centers (n = 44). Among survivors, neurodevelopmental disability was most
      common (12/44; 27%) followed by gastrointestinal (9; 20.5%), pulmonary (5;
      11.4%), musculoskeletal (5; 11.4%), and cardiac (2; 4.5%). Additional surgery was
      required in 17 patients (38.6%), including recurrent CDH repair in 7 (15.9%).
      Five patients (11.4%) had hearing loss. Among 41 children with available 24-month
      data, 32 (78%), 17 (41.5%), and 14 (34.1%) patients had weights below the 50th,
      25th, and 3rd percentiles, respectively. CONCLUSION: Congenital diaphragmatic
      hernia survivorship is associated with significant disability. Standardization of
      follow-up practices is essential to enable population-based outcomes analysis.

PMID- 22595558
TI  - Chylothorax after congenital diaphragmatic hernia repair: a population-based
      study.
AB  - PURPOSE: Chylothorax is a recognized complication of congenital diaphragmatic
      hernia (CDH) repair. Our aims were to describe the frequency and outcomes of
      chylothorax and to seek predictors of chylothorax occurrence within a population
      based CDH cohort. METHODS: Records for patients with CDH born between 2006 and
      2010 were abstracted from a national database and were compared according to
      presence/absence of postrepair chylothorax. Univariate, and where appropriate,
      multivariate analyses were performed for group comparisons and chylothorax
      outcome prediction. RESULTS: Of 243 newborns with CDH surviving to repair, 11
      (4.5%) developed a chylothorax. All were managed nonoperatively. Factors
      predictive of chylothorax outcome on multivariate analysis included need for
      preoperative transfusion (odds ratio, 13.2; 95% confidence interval, 2.1-83.7; P
      = .006) and preoperative high-frequency oscillatory ventilation (odds ratio, 7.1;
      95% confidence interval, 1.6-31.2; P = .01). Preoperative vasopressor use was
      significant on univariate analysis only. The groups were comparable for survival,
      length of stay, and duration of ventilation, but chylothorax patients had
      prolonged total parenteral nutrition (53 vs 21 days, P = .006) and more central
      line days (46 vs 24 days, P = .03). CONCLUSIONS: Our data suggest that severity
      of preoperative cardiopulmonary derangement and not anatomical or technical
      factors predicts chylothorax occurrence after CDH repair.

PMID- 22595559
TI  - Alterations of peroxisome proliferator-activated receptor gamma and monocyte
      chemoattractant protein 1 gene expression in the nitrofen-induced hypoplastic
      lung.
AB  - BACKGROUND/PURPOSE: Peroxisome proliferator-activated receptor gamma (PPARgamma)
      plays a key role in normal lung development. Peroxisome proliferator-activated
      receptor gamma messenger RNA (mRNA) is detectable at 18 days of gestation in
      fetal rat lungs, and levels peak just before birth. Peroxisome proliferator
      activated receptor gamma agonists are reported to stimulate lung development,
      whereas inhibition of PPARgamma disrupts postnatal lung maturation. Monocyte
      chemoattractant protein 1 (MCP-1), which is inhibited by PPARgamma, is reported
      to disrupt late lung morphogenesis. This study was designed to investigate the
      hypothesis that PPARgamma expression is downregulated and that MCP-1 expression
      is upregulated during the late stages of lung development in nitrofen-induced
      hypoplastic lungs. METHODS: Pregnant rats were treated with nitrofen or vehicle
      on D9. RNA was extracted from fetal lungs (D18 and D21), and relative mRNA
      expression levels of PPARgamma and MCP-1 were determined by reverse transcriptase
      polymerase chain reaction. Immunohistochemistry was performed to evaluate protein
      expression/distribution of PPARgamma and MCP-1. RESULTS: Relative mRNA expression
      levels of PPARgamma were significantly downregulated in the nitrofen group
      compared with controls on D21, whereas MCP-1 levels were upregulated.
      Immunohistochemical study showed markedly decreased PPARgamma and increased MCP-1
      immunoreactivity in the nitrofen-induced hypoplastic lungs compared with controls
      on gestational day 21. CONCLUSION: Altered pulmonary gene expression of PPARgamma
      and MCP-1 during late gestation may impair lung development and maturation,
      contributing to pulmonary hypoplasia in the nitrofen-induced congenital
      diaphragmatic hernia model.

PMID- 22595560
TI  - Does earlier lobectomy result in better long-term pulmonary function in children
      with congenital lung anomalies? A prospective study.
AB  - BACKGROUND: Management of asymptomatic congenital pulmonary airway malformations
      remains controversial when addressing the optimal timing of surgical resection.
      Neonatal resection is advocated by some based on the theory that earlier
      lobectomy results in greater compensatory lung growth. We examined whether age at
      lobectomy is correlated with better pulmonary outcomes as reflected by pulmonary
      function and exercise testing. METHODS: Patients who had lobectomy for congenital
      pulmonary airway malformation between 1985 and 2002 were identified and underwent
      detailed clinical history, physical examination, pulmonary function testing
      (total lung capacity, forced vital capacity, forced expiratory volume in 1
      second), and exercise testing (power, maximal oxygen uptake [Vo(2)max]). RESULTS:
      Of 87 patients identified, 47 met the inclusion criteria, and 28 were tested
      prospectively. Age at the time of lobectomy ranged from 3 days to 56 months.
      There was no correlation between age at lobectomy and pulmonary function (total
      lung capacity, P = .408; forced vital capacity, P = .319; forced expiratory
      volume in 1 second, P = .174) or maximal work capacity (power, P = .280). There
      was a trend toward lower Vo(2)max in patients who had undergone lobectomy at an
      older age (Vo(2)max, P = .055). CONCLUSION: Most children undergoing lobectomy
      have normal long-term pulmonary function. We found no correlation between age at
      lobectomy and future pulmonary function. Cardiopulmonary exercise testing should
      be considered in evaluating functional outcome in these patients.

PMID- 22595561
TI  - Thoracoscopic vs open resection of congenital lung lesions: a meta-analysis.
AB  - BACKGROUND: Several comparative studies are published evaluating both the open
      and the minimally invasive approaches for congenital lung lesions with
      inconsistent results. Our objective was to compare both procedures using
      systematic review and meta-analysis methodology. METHODS: All publications
      describing both interventions were reviewed. The statistical analysis was
      performed using RevMan 5 software (Cochrane library). MAIN RESULTS: No randomized
      trials were identified. Six retrospective studies were identified and were
      included in this study. There was no significant difference in overall
      complication rates between both techniques. Lengths of hospital stay as well as
      days with chest tube in place were longer with the open approach. There was no
      difference in the duration of surgery. Postoperative pain management was
      heterogeneous between studies. No study looked at long-term follow-up. Subgroup
      analysis for congenital cystic adenomatoid malformation of the lung was done.
      CONCLUSIONS: Our results suggest no differences between thoracotomy versus
      thoracoscopy for congenital lung lesions with respect to overall complications
      and the duration of surgery. However, length of hospital stay and days with chest
      tube in place were longer after the open approach. Thoracoscopic resection is a
      safe and feasible alternative to open resection of congenital lung lesions in
      experienced hands.

PMID- 22595562
TI  - Pectus carinatum treatment in Canada: current practices.
AB  - BACKGROUND: Multiple treatment options currently exist for the correction of
      pectus carinatum (PC). We performed a survey of Canadian pediatric surgeons to
      define current practices. METHODS: All active members of Canadian Association of
      Paediatric Surgeons were surveyed online during winter 2011 through the Canadian
      Association of Paediatric Surgeons Web site. The survey assessed multiple facets
      of PC evaluation and treatment, with particular emphasis on the practice of
      bracing. RESULTS: Forty-five active members (85%) responded, of whom 32 (71%)
      currently treat PC. Fifty-three percent of practices are low volume (<5 patients
      annually). In terms of preferred or most used treatment modality, 69% of surgeons
      used bracing, 25% performed Ravitch repairs, 3% performed open minimal cartilage
      resections, and 3% performed reverse Nuss procedures. Of 23 surgeons (72%) who
      used bracing, 83% used it for most or the patients. Fifty-seven percent judged
      their bracing results as good or excellent, and 74% felt that most or all
      patients braced were satisfied; 80% and 88% agreed or strongly agreed that
      bracing was generally preferable to surgical repair and that bracing should be
      first line treatment, respectively. CONCLUSIONS: Bracing is the preferred
      treatment for PC by most Canadian pediatric surgeons, despite lack of prospective
      outcome data. This presents an opportunity for a multicenter prospective study.

PMID- 22595563
TI  - An innovative method of pediatric chest wall reconstruction using Surgisis and
      swinging rib technique.
AB  - PURPOSE: Herein, we describe a new surgical approach for chest wall
      reconstruction using a native supporting rib and Surgisis. METHODS: A
      retrospective review of 3 cases from 2 tertiary pediatric health care centers
      presenting with chest wall defects in the neonatal period was performed.
      Perioperative data were collected. RESULTS: Two chest wall deformities were
      diagnosed at birth (Poland syndrome and cleft sternum). One patient was diagnosed
      prenatally with a mediastinal mass. The first infant had absent ribs 2 through 9.
      He underwent chest wall reconstruction at 4 weeks of life because of difficulty
      weaning from ventilation related to paradoxical breathing. The hamartoma of the
      second asymptomatic patient was removed at 6 weeks. The third patient's V-shaped
      sternal defect encompassed through the upper two thirds of the sternum and was
      repaired at 6 months of age with intraoperative transesophageal echocardiogram
      monitoring. In all cases, Surgisis (collagen matrix) was used as an onlay patch.
      In 2 cases, a swinging rib acted supportive. Neither patient had intraoperative
      complications. CONCLUSION: Surgisis is useful in pediatric chest wall
      reconstruction, particularly in combination with swinging ribs. The capacity for
      adaptation to the child's growth of this approach is crucial. Short-term safety
      is shown, but long-term assessment is required.

PMID- 22595564
TI  - Effects of sodium hydroxide exposure on esophageal epithelial cells in an in
      vitro ovine model: implications for esophagus tissue engineering.
AB  - BACKGROUND: Esophagus tissue engineering holds promises for esophageal
      replacement after severe caustic injuries. The aim of this study was to determine
      whether viable esophageal epithelial cells could be isolated from an esophagus
      exposed to varying concentrations of alkali with regard to number, viability, and
      morphology during in vitro culture. METHODS: Ovine esophagi were exposed to
      phosphate-buffered saline 2.5%, 15%, or 25% sodium hydroxide (NaOH). The effect
      of NaOH concentrations on epithelial damage was assessed histologically.
      Esophageal epithelial cells were then isolated, and cell count and viability were
      investigated. Finally, cell number, viability, and morphology of esophageal
      epithelial cells were determined for 24 days of in vitro culture. RESULTS:
      Histologic analysis showed a progressive destruction of the epithelium
      proportional to increasing NaOH concentrations. Esophagi treated with phosphate
      buffered saline and 2.5% NaOH showed significantly higher viable cell counts
      after isolation and culture in comparison with those treated with 15% to 5% NaOH.
      CONCLUSION: The evidence presented in this study indicates that epithelial
      biopsies from an esophagus exposed to low concentrations (2.5%) of NaOH will
      still yield large numbers of viable cells suitable for tissue engineering
      applications. In cases of exposure to higher concentrations (15%-25%),
      alternative cell sources for epithelial regeneration, such as stem cells, will be
      necessary for tissue engineering applications.

PMID- 22595565
TI  - An analysis of early nonmortality outcome prediction in esophageal atresia.
AB  - BACKGROUND: Advances in care for neonates with esophageal atresia (EA) has
      improved overall survival rates. Disease-specific prognostic scores for EA assess
      mortality risk without assessing patient morbidity. We undertook an analysis of
      these and generic scoring systems evaluating their ability to predict early
      nonmortality outcomes. METHODS: We conducted a retrospective review of all
      patients with EA at our tertiary care children's hospital. Disease-specific
      (Spitz, Waterston, and Montreal) and generic prognostic scores (Score for
      Neonatal Acute Physiology II and Score for Neonatal Acute Physiology-Perinatal
      Extension) were calculated. Outcomes investigated included mortality and early
      nonmortality outcomes (leak, stricture, and recurrent fistula). These were
      assessed individually and as a composite "poor outcome" score. Correlations were
      sought, and receiver operating characteristic curves were generated. RESULTS:
      Fifty patients were included for analysis, with 5 deaths (10%) in our series.
      Eight patients developed a postoperative leak, 18 developed stenosis requiring
      dilatation, and 2 developed refistulization. Overall, 51% of survivors had a poor
      composite outcome. Although no prognostic score achieved statistical
      significance, the generic scores outperformed the disease-specific scores in
      predicting early nonmortality outcomes. CONCLUSIONS: Postoperative morbidity
      remains common in patients with EA. Disease-specific, preexisting prognostic
      scoring systems do not delineate surviving patients at risk for early
      complications and appears to underperform when compared with generic prognostic
      scores.

PMID- 22595566
TI  - Role of endoscopic retrograde cholangiopancreatography in diagnosis and
      management of congenital choledochal cysts: 28 pediatric cases.
AB  - BACKGROUND/PURPOSE: Management of choledochal cysts consists of surgical excision
      and hepaticojejunal anastomosis. Endoscopic retrograde cholangiopancreatography
      (ERCP) can be used to resolve complications and to evaluate the biliary tract and
      pancreatobiliary duct junction. Our aim was to underline the importance of ERCP
      for optimal management. METHODS: From 2005 to 2011, 28 patients were reviewed (21
      female, 7 male; mean age, 5.71 years; range, 2-16 years). After imaging, all
      patients underwent elective ERCP and were referred for surgery. RESULTS:
      Choledochal cyst was diagnosed at ultrasound and magnetic resonance
      cholangiopancreatography in all examined patients; common biliopancreatic duct
      was diagnosed in 3 (20%) of 15 patients at magnetic resonance
      cholangiopancreatography and in none at ultrasound. Endoscopic retrograde
      cholangiopancreatography showed choledochal cyst in all patients and common
      biliopancreatic duct in 19 (68%) of 28 patients. Twelve patients underwent
      sphincterotomy. All patients underwent surgical extrahepatic biliary tree
      resection and hepaticojejunal anastomosis. Mean period of hospitalization was 9.5
      days (range, 6-13 days). No major complications related to ERCP were observed.
      Two patients needed postoperative ERCP for complications (pancreatitis during
      follow-up). CONCLUSIONS: In our pediatric experience, ERCP is feasible and safe.
      It can rule out other possible biliary tract anomalies and help plan the timing
      and choice of the appropriate surgical procedure.

PMID- 22595567
TI  - Reduced aluminum contamination decreases parenteral nutrition associated liver
      injury.
AB  - PURPOSE: Parenteral nutrition-associated cholestasis remains a significant
      problem, especially for the surgical neonates. Aluminum is a toxic element known
      to contaminate parenteral nutrition. We hypothesize that parenterally
      administered aluminum causes liver injury similar to that seen in parenteral
      nutrition-associated cholestasis. METHODS: Twenty 3- to 6-day-old domestic pigs
      were divided into 5 equal groups. A control group received daily intravenous 0.9%
      NaCl. Each subject in experimental groups received intravenous aluminum chloride
      at 1500 MUg kg(-1) d(-1) for 1, 2, 3, or 4 weeks. At the end of the study, blood
      was sampled for direct bilirubin and total bile acid levels. Liver, bile, and
      urine were sampled for aluminum content. Liver tissue was imaged by transmission
      electron microscopy for ultrastructural changes. RESULTS: Transmission electron
      microscopy revealed marked blunting of bile canaliculi microvilli in all
      experimental subjects but not the controls. Serum total bile acids correlated
      with the duration of aluminum exposure. The hepatic aluminum concentration
      correlated with the duration of aluminum exposure. CONCLUSIONS: Parenterally
      infused aluminum resulted in liver injury as demonstrated by elevated bile acids
      and by blunting of the bile canaliculi microvilli. These findings are similar to
      those reported in early parenteral nutrition-associated liver disease.

PMID- 22595568
TI  - Food aversion among patients with persistent hyperinsulinemic hypoglycemia of
      infancy.
AB  - INTRODUCTION: Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is the
      most common cause of neonatal hypoglycemia. Feeding plays a major role in its
      management. We evaluated the magnitude of food aversion among our patients with
      PHHI. METHODS: A retrospective medical record review was conducted for patients
      with PHHI managed during the last 15 years. Demographic and clinical data were
      retrieved, and descriptive data were generated. RESULTS: Forty-two patients (18
      were male and 24 were female) were managed for PHHI over the study period. Thirty
      three patients had subtotal pancreatectomy, and 9 were managed medically, with a
      mean follow-up of 5 years. Nineteen patients (45%) had aversion to food, and 9 of
      them were developmentally delayed. Of 14 patients assessed by a speech
      pathologist, 5 had aversive sensory behavior, 4 had dysfunctional pharyngeal
      swallowing, and 5 had a normal assessment. Ten were managed with oral feeding, 4
      had gastrostomy feedings, and 5 were managed with oral and nasogastric tube feeds
      for various periods. CONCLUSIONS: Food aversion is significantly prevalent among
      patients with PHHI. The presence of food aversion appears to be independent of
      developmental delay. Aggressive measures to manage food aversion could help in
      the management of patients with PHHI.

PMID- 22595569
TI  - Single-incision laparoscopic splenectomy in children.
AB  - PURPOSE: Single-incision laparoscopic surgery is being incorporated into the
      practices of many pediatric surgeons. Its superior cosmetic outcomes have
      resulted in increased patient- and parent-driven demand for the approach. This
      article describes a series of single-incision laparoscopic splenectomies (SSs) in
      children and compares outcomes with a historical series of standard laparoscopic
      splenectomies (LS). METHODS: The medical records of patients who underwent
      standard splenectomy and SS at our institution between 2007 and 2010 were
      reviewed. Perioperative data were recorded. Descriptive comparisons were made
      between the SS and LS groups. RESULTS: Seven patients underwent SS, and 4
      underwent LS during the study period. Operative times for the SS group decreased
      as experience with the procedure accumulated and ultimately approached LS
      operative times. No conversions to a standard laparoscopic or open approach were
      required. No complications occurred. Length of stay and postoperative pain were
      similar in both groups. single-incision laparoscopic splenectomy provided
      excellent cosmetic outcomes. CONCLUSIONS: Single-incision laparoscopic
      splenectomy is feasible in children. Its main benefit is improved cosmesis. It
      can be performed without detrimental increases in operative times or patient
      discomfort. Given an increased demand for the approach, it remains a viable
      option in children.

PMID- 22595570
TI  - Surgery for suspected rotation abnormality: selection of open vs laparoscopic
      surgery using a rational approach.
AB  - BACKGROUND: Laparoscopy is increasingly used for children with suspected rotation
      abnormalities. However, indications for open and laparoscopic approaches are not
      well defined. We reviewed our experience with both open and laparoscopic
      approaches to develop a rational approach to these patients. METHODS: Charts of
      all children undergoing surgery for a suspected rotation abnormality for 10 years
      were retrospectively reviewed. RESULTS: There were 173 patients. Of 73 neonates
      presenting with suspected volvulus, 71 underwent initial laparotomy and 2 were
      converted from initial laparoscopy. Eighty percent underwent Ladd procedure, 64%
      had volvulus, and 2 died of midgut volvulus. Of 18 neonates presenting without
      suspected volvulus, 14 underwent initial laparotomy and 4 had a laparoscopic
      approach with 1 conversion to laparotomy. Seventy-eight percent underwent Ladd
      procedure, and 22% had volvulus. Of the 82 older patients, 37 underwent
      laparotomy and 45 had initial laparoscopy, 8 of which were converted. Sixty-seven
      percent underwent Ladd procedure, and 28% had volvulus. Postoperative
      complication rate, median time to full diet, and median hospital stay were
      comparable with those previously reported in the literature. CONCLUSION: Based on
      our results, we advocate open surgery for neonates with suspected volvulus.
      Laparoscopy represents an excellent alternative for older children and for
      neonates presenting without suspected volvulus.

PMID- 22595571
TI  - Associated malformations and the "hidden mortality" of gastroschisis.
AB  - BACKGROUND: Little is known about associated anomalies in fetuses with
      gastroschisis (GS) who experience an "atypical perinatal event," defined as
      spontaneous abortion, stillbirth, termination, or death within 24 hours of birth.
      PURPOSE: This study aims to compare associated malformation rates in an atypical
      perinatal event cohort vs newborns with GS surviving longer than 24 hours.
      METHODS: A national prospective GS database was analyzed for cases with an
      atypical perinatal event. Associated anomaly rates were compared between this
      cohort and babies surviving longer than 24 hours. RESULTS: Twenty-three atypical
      perinatal events (2 spontaneous abortions, 7 stillbirths, 11 terminations, and 3
      deaths within 24 hours) were identified from 529 total GS cases. Autopsies in 14
      (61%) of 23 identified at least 1 anomaly (excluding intestinal, patent ductus
      arteriosus, and undescended testicle) in 11 (78.6%) and a "lethal" anomaly in 4
      (36%). The associated anomaly rate in newborns surviving longer than 24 hours was
      7.3% (37/506; P < .0001). The anomalies in the atypical perinatal event cohort
      were musculoskeletal (35%), cardiac, central nervous system, pulmonary, and
      genitourinary (12% each). Among survivors, the most common anomalies were cardiac
      (38%), genitourinary (32%), musculoskeletal (16%), and central nervous system
      (8%). CONCLUSION: Rates of associated anomalies are significantly higher in
      fetuses experiencing atypical perinatal events and may represent the "hidden
      mortality" of GS.

PMID- 22595572
TI  - Evaluation of Surgisis for patch repair of abdominal wall defects in children.
AB  - BACKGROUND: Abdominal wall defects in children are not always amenable to primary
      repair and may require a patch. The ideal material has yet to be established. We
      sought to evaluate our experience using the bioabsorbable material Surgisis (Cook
      Surgical, Bloomington, IN) for abdominal closure. METHODS: A retrospective chart
      review of abdominal wall defects repaired with Surgisis in our institution from
      2000 to 2010 was performed. Data extracted included cause of defect, age at
      operation, possibility of skin coverage, recurrence, length of follow-up, and
      rate of wound infection. RESULTS: Thirteen patients were identified. Cause of
      defect was gastroschisis (n = 2), ventral hernia after diaphragmatic hernia
      repair (n = 2), and omphalocele (n = 9). At median follow-up of 60 months (range,
      10-90), 5 (38%) of 13 patients recurred, and 1 patient recurred twice. All
      recurrences required subsequent patch closure. Six instances of wound infection
      required antibiotics. None required patch removal. There was a trend toward more
      frequent recurrence among infants undergoing patch repair (3/4 recurrences in
      this group) than neonates (1/4 recurrences) or children older than 18 months (1/5
      recurrences). CONCLUSION: Our data suggest that Surgisis is moderately successful
      in the repair of pediatric abdominal wall defects. We noted a trend toward a
      higher recurrence rate in infants. Further studies investigating timing of repair
      and alternative biosynthetic materials are warranted.

PMID- 22595573
TI  - EphB2/B3 gene expression is down-regulated during early embryogenesis in the
      cadmium-induced omphalocele chick model.
AB  - PURPOSE: In the chick embryo, the administration of cadmium (Cd) induces
      omphalocele phenotype. The earliest histologic change in this model is observed
      in the somite 4 hours (H) post treatment, postulating that disruption of somite
      development in embryogenesis may cause omphalocele phenotype. EphB2 and EphB3 are
      involved in many embryonic developmental processes, including somitogenesis.
      EphB2(-/-)EphB3(-/-) double knockouts display omphalocele phenotype. We
      hypothesized that EphB2/B3 genes are down-regulated in the Cd chick model during
      the critical period of embryogenesis. METHODS: After 60H incubation, chicks were
      harvested 1H, 4H, and 8H post treatment with saline or Cd and divided into
      control and Cd groups. Reverse transcriptase-polymerase chain reaction was
      performed to evaluate gene expression levels of EphB2/B3. Immunofluorescence
      confocal microscopy was performed to evaluate protein expression/distribution of
      EphB2/B3. RESULTS: At 4H post treatment, the messenger RNA expression levels of
      EphB2/B3 were significantly down-regulated in the Cd group compared with controls
      (P < .05). The intensity of EphB2/B3 immunofluorescence was markedly diminished
      at 4H in the Cd-treated embryos, whereas strong immunoreactivity was observed in
      the somite in controls. CONCLUSION: Downregulation of EphB2/B3 during the narrow
      window of early embryogenesis may interfere with normal somitogenesis, preventing
      migration of embryonic body wall ventrally and thus causing omphalocele.

PMID- 22595574
TI  - Predictors of failed enema reduction in childhood intussusception.
AB  - BACKGROUND: Initial management of intussusception is enema reduction. Data are
      scarce on predicting which patients are unlikely to have a successful reduction.
      Therefore, we reviewed our experience to identify factors predictive of enema
      failure. METHODS: A retrospective review of all episodes of intussusception over
      the past 10 years was conducted. Demographics, presentation variables, colonic
      extent of intussusceptions, and hospital course were collected. Extent of
      intussusception was classified as right, transverse, descending, and
      rectosigmoid. Episodes were grouped as success or failure of enema reduction and
      compared using the Student t test for continuous variables and chi(2) test for
      dichotomous variables. Significance was P less than .05. RESULTS: We identified
      405 episodes of intussusception and 371 attempts at enema reduction. There were
      285 successful enema reductions. There was no difference between groups in age;
      sex; or the presence of emesis, fever, or abdominal mass. The failed enema group
      was more likely to have had symptoms over 24 hours before presentation (P =
      .006), bloody diarrhea (P < .001), and lethargy (P < .001). The chance of success
      diminished with colonic extent (right, 88%; transverse, 73%; left, 43%;
      colorectal, 29%; P < .001). CONCLUSION: Predictors of failed enema reduction of
      intussusception include presence of symptoms over 24 hours, diarrhea, lethargy,
      and distal extent of intussusception.

PMID- 22595575
TI  - Antibiotics administration before enema reduction of intussusception: is it
      necessary?
AB  - BACKGROUND: Some centers advocate using antibiotics before enema reduction to
      prevent septic complications. Our objective was to determine whether using
      antibiotics before reduction provided any improvement in outcomes. METHODS: With
      institutional review board approval, patients from 2 centers were compared: 1
      where antibiotics were administered, and one where they were not. This
      retrospective cohort study from January 2005 to December 2010 evaluated
      demographic data, episodes of postreduction fever, hospital stay, and analgesia
      requirements. RESULTS: One hundred eighteen patients were identified: 83 males
      (70.3%) and 35 females (29.7%). The median age was 24 months (range, 1-180).
      Fifty-six patients (57.7%) received antibiotics, whereas 41 (42.7%) did not.
      Twenty-one patients (17.8%) had missing data and were excluded. The incidence of
      fever postreduction was not statistically different between groups: 12.8% for
      those who received antibiotics vs 17.9% for those who did not (P = .7367). No
      adverse antibiotic reactions were reported. Average time to oral feeds was 7.3 vs
      10.6 hours (P = .06), and the length of stay was 1.7 vs 1.4 days (P = .07).
      CONCLUSION: Although antibiotics are administered routinely in some centers, they
      appear of little value. Financial costs and potential adverse reactions must be
      considered. Further prospective evaluation is being conducted using a larger
      sample size to confirm these results.

PMID- 22595576
TI  - Five-year outcomes after serial transverse enteroplasty in children with short
      bowel syndrome.
AB  - AIM: The aim of this study is to report 5-year outcomes in patients who have
      received serial transverse enteroplasty (STEP) using clinical and biochemical
      assessments of intestinal function. METHODS: Thirty-one STEP procedures have been
      performed at our institution. Twelve patients who received STEP before January
      2005 were analyzed. Clinical and biochemical outcomes were performed pre-STEP and
      post-STEP on an annual basis. Paired t tests were used to compare post-STEP
      outcomes to pre-STEP values (P < .05 was significant). MAIN RESULTS: There were
      12 patients (3 females; median age, 5.5 months). Serial transverse enteroplasty
      resulted in mean increase in length of dilated bowel segment of 89% +/- 26% and
      increase in total small bowel length of 46% +/- 40%. Two patients received liver
      intestinal transplants post-STEP (at 4 and 5 months), and 2 patients died of
      liver failure at 3 and 8 months. The remaining 8 of 12 patients all show stable
      intestinal absorptive capacity (data not shown). Of 8 patients, 7 were weaned off
      parenteral nutrition by 4 years. No patient has required repeat STEP or bowel
      tapering. Two patients developed staple line leak, and 1 patient developed
      gastrointestinal bleed from staple line ulcers. CONCLUSION: This report
      represents the largest series of STEP patients followed up beyond 5 years. Long
      term clinical, biochemical, and radiologic outcomes appear to be robust.

PMID- 22595577
TI  - The next step? Use of tissue fusion technology to perform the serial transverse
      enteroplasty--proof of principle.
AB  - BACKGROUND: Serial transverse enteroplasty (STEP) is an established procedure for
      intestinal lengthening and tapering. A gastrointestinal linear stapler is used to
      taper the bowel sequentially. We report preliminary experience with tissue fusion
      technology to perform STEP in a porcine model. METHODS: Four weaned male pigs
      (mean age, 4 +/- 0 weeks; mean weight, 6.8 +/- 0.1 kg) first underwent a 60-cm
      reversed intestinal segment followed by a STEP 4 to 6 weeks later. The LigaSure
      Impact (Covidien, Valleylab, Tyco Healthcare Group LP, Boulder, CO) was used to
      perform the procedure. Animals were fed on postoperative day 2 and terminated 1
      week later. Morphometric data were collected, and intestinal tissue was obtained
      for histology. RESULTS: Mean bowel caliber of 5.1 +/- 0.5 cm was tapered to 1.8
      +/- 0.3 cm post-STEP with a mean increase in the length of the dilated segment of
      82% +/- 20%. All animals tolerated enteral feeding, and all survived to
      termination on day 7. Histologic evaluation revealed the zone of tissue fusion to
      be 7.1 +/- 1.5 mm. Masson trichrome, hematoxylin and eosin, and polarized
      picrosirius red stains demonstrated that the fusion zone was well healed with
      overlying granulation tissue. CONCLUSION: This is the first report of the
      successful application of radiofrequency energy to perform the STEP procedure in
      animals. Although further evaluation is required, tissue fusion devices may
      eventually provide an alternative to the linear stapler for the STEP procedure.

PMID- 22595578
TI  - Strictureplasty and intestinal resection: different options in complicated
      pediatric-onset Crohn disease.
AB  - BACKGROUND/PURPOSE: Surgical resection or strictureplasty (SP) are different
      options for intestinal Crohn disease (CD) strictures. The aim of this article is
      evaluation of long-term outcome of SP and resection. METHODS: From 1996 to 2011,
      39 patients (23 male, 16 female) with symptomatic ileal and ileocolonic CD
      strictures resistant to medical/nutritional therapy and treated with surgery in 2
      different surgical units were reviewed. The mean age at diagnosis was 11.82 years
      (range, 4-17 years). Mean age at surgery was 15.94 years (range, 4-24 years).
      Mean follow-up was 6.88 years (range, 0.5-15 years). Patients underwent resection
      (group A) or different SP techniques (group B). RESULTS: Twenty patients
      underwent intestinal resection (ileal or ileocolonic resection), and 19 patients
      underwent SP (jejunal, ileal, or ileocolic). Early postsurgical complications
      were observed in 2 patients of group A. Follow-up of group A patients revealed
      that 1 patient needed emergency treatment after 8 months surgery because of
      adhesions and 1 patient developed recurrence treated with medical therapy. In the
      follow-up group B, 3 patients experienced disease recurrence, 2 of them at the
      site of previous surgery. CONCLUSIONS: At long-term follow-up, no significant
      difference in relapsing rate was observed between the 2 groups. Strictureplasty
      and resection represent an effective treatment of pediatric CD strictures.
      Strictureplasty could represent the first option for intestinal preservation.

PMID- 22595579
TI  - Surgical management of gastrointestinal basidiobolomycosis in pediatric patients.
AB  - INTRODUCTION: Gastrointestinal basidiobolomycosis (GIB) is a rare fungal disease.
      We reviewed our experience with this disease over the last 10 years, with special
      emphasis on the surgical aspects. METHODS: A retrospective chart review was
      conducted for pediatric patients with GIB who were managed at our institution
      over the last 10 years. Demographic, clinical, and follow-up data were collected,
      and descriptive data were generated. RESULTS: Nine patients with a median age of
      7 years were managed for GIB over the study period. Six patients were managed
      surgically. Four had colonic and liver involvement, 1 had a left hepatic lesion,
      and 1 had a porta hepatic mass. One patient had multiple liver lesions and was
      managed medically, and 2 patients had disseminated disease and died shortly after
      presentation. Tissue biopsies confirmed the diagnosis, and all received
      antifungal treatment. Patients were followed up for a median of 6 years. All live
      patients are free of disease, and 4 are still on antifungal medications.
      CONCLUSIONS: Gastrointestinal basidiobolomycosis is an aggressive disease that
      requires early surgical intervention to avoid complications and hasten disease
      eradication. Long-term follow-up is warranted, given the significant potential
      for complications.

PMID- 22595580
TI  - The impact of variation in access to care on the management of Hirschsprung
      disease.
AB  - INTRODUCTION: Variation in access to care has a significant impact on the disease
      management process and outcomes. Variable access to care might have similar
      effects on the management of Hirschsprung disease (HD). However, such variation
      has not been highlighted. MATERIALS AND METHODS: All patients referred to 3
      academic centers (ACs) with HD were reviewed. Patient presentations, referral
      patterns, timing, and type of surgical intervention were compared between
      patients born in AC and those born in non-AC. Babies born with major congenital
      anomalies (MCAs) or total colonic HD were excluded. RESULTS: Between 1998 and
      2011, 129 patients were identified. After excluding 30 patients, 99 were split
      into 20 inborn patients (AC) and 79 outborn patients. Outborn patients more often
      presented with constipation (95% vs 65%, P = .001), whereas inborn patients
      presented with feeding intolerance or vomiting (75% vs 39%, P = .004). Outborn
      patients were diagnosed and had their pull-through (PT) at an older median age
      (in days) of 186 (1-2621) vs 4.5 (1-451) (P = .001) and 345 (11-2757) vs 92 (3
      928) (P = .001), respectively. Moreover, inborn patients were more likely to
      undergo primary PT (75% vs 46%, P = .02) and avoid bowel diversion (95% vs 66%, P
      = .02). CONCLUSION: Variation in access to care can have a significant impact on
      the quality of care delivery in HD. Limited access to AC is associated with
      staged PT in addition to delay in the diagnosis and management.

PMID- 22595581
TI  - Three-dimensional endoanal ultrasound and anorectal manometry in children with
      anorectal malformations: new discoveries.
AB  - BACKGROUND/PURPOSE: Fecal incontinence and constipation are common problems in
      follow-up of anorectal malformations (ARMs). We evaluated the anal sphincters
      using the 3-dimensional endoanal ultrasonography (3D-EAUS) and the anorectal
      manometry after ARMs repair. METHODS: Seventeen patients, divided into 3 groups
      according to Wingspread classification, underwent anorectal manometry and 3D
      EAUS. Clinical, manometric, and endosonographic scoring systems were used.
      RESULTS: The average anal resting pressure (aARP) was significantly higher in low
      ARMs than in intermediate and high ARMs. The anal squeeze pressure was not
      statistically different between the 3 groups. Three-dimensional EAUS visualized
      internal anal sphincter (IAS) disruptions in 7 of 17 patients and absence of IAS
      in 6 of 17 children with high ARMs. Scars of the external anal sphincter were
      localized in low ARMs and generalized in the other groups. In the case of IAS
      disruption with aARP greater than 20 mm Hg, fecal incontinence and constipation
      improved with biofeedback and/or laxatives, whereas daily enemas were necessary
      in absence of IAS with aARP less than 20 mm Hg. Statistical correlation was
      observed between endosonographic and manometric findings and clinical outcomes.
      CONCLUSIONS: Lesions of the anal sphincter are common in ARMs. Three-dimensional
      EAUS and anorectal manometry ensure a complete assessment of the anal sphincter
      and could provide useful information to define the most appropriate treatments to
      improve the quality of life.

PMID- 22595582
TI  - Parent health literacy and satisfaction with plain language education materials
      in a pediatric surgery outpatient clinic: a pilot study.
AB  - BACKGROUND: Although significant, the issue of health literacy (HL) among parents
      attending pediatric surgery outpatient clinics has received little attention.
      PURPOSE: The objectives of this study are to determine the HL skills of parents
      attending the pediatric surgery outpatient clinic at McMaster Children's Hospital
      and to describe parent satisfaction with plain language materials. METHODS: This
      cross-sectional study was conducted at the pediatric surgery outpatient clinic at
      McMaster Children's Hospital. Using convenience sampling for 4 months, parents
      were recruited and interviewed regarding their demographic status. The Newest
      Vital Sign tool was used to assess HL. Feedback on the plain language education
      material was received. RESULTS: Seventy-nine individuals were recruited, with a
      recruitment rate of 62%. Seventy-one percent had adequate HL. English as a first
      language and Canada as the place of birth were significantly correlated with
      adequate HL (r = 0.367, P < .001; r = 0.259, P < .05). Parents reported
      satisfaction with the plain language material, regardless of their HL level.
      CONCLUSION: Twenty-nine percent of parents showed inadequate HL, likely an
      underestimate owing to study limitations. Parents expressed satisfaction with the
      plain language material, emphasizing the need for clear, effective communication
      with patients and families. Future directions include evaluating staff knowledge
      of a universal precautions approach to health communication and the accessibility
      of plain language materials.

PMID- 22595583
TI  - The intrathoracic kidney: should we fix it?
AB  - BACKGROUND: Intrathoracic kidney is a rare congenital anomaly, with only 13 cases
      reported in the pediatric age group over the past 25 years. The relevant
      literature is limited to individual case reports or small case series with no
      follow-up data. Both operative and nonoperative management has been advocated. We
      report our experience in the management of children with an intrathoracic kidney
      as well as the efficacy of nonoperative management in select patients. METHODS:
      Five cases of intrathoracic kidney were collected prospectively since 1992 and
      carefully followed up long term. RESULTS: Two children presented with acute
      respiratory distress and underwent right diaphragmatic hernia repair and
      nephropexy. Incidental diagnosis of a left intrathoracic kidney was made in 3
      children. Long-term follow-up has demonstrated normal function and development of
      these kidneys in all 5 children with no late bowel herniation in the nonoperative
      group. CONCLUSION: Intrathoracic kidney associated with bowel in the chest should
      undergo standard repair and nephropexy. An isolated intrathoracic kidney without
      evidence of bowel herniation can safely be observed. This is the largest
      pediatric series of intrathoracic kidney as well as the first to document the
      efficacy of nonoperative management with long-term follow-up.

PMID- 22595584
TI  - Evaluation of a new pediatric intraosseous needle insertion device for low
      resource settings.
AB  - BACKGROUND AND PURPOSE: The Near Needle Holder (NNH) (Near Manufacturing,
      Camrose, Alberta, Canada) is a reusable tool to introduce a standard hollow
      needle for pediatric intraosseous (IO) infusion. We compared the NNH to the Cook
      Dieckmann (Cook Critical Care, Bloomington, IN) manual IO needle in a simulation
      setting. METHODS: Study subjects were 32 physicians, nurses, and medical students
      participating in a trauma course in Guyana. After watching a training video and
      practicing under supervision, subjects were observed inserting each device into a
      pediatric leg model using a randomized crossover design. Outcome measures were
      time to successful insertion, technical complications, ease of use, and safety of
      each device. RESULTS: The mean time for IO insertion (32 +/- 13 seconds) was
      similar for both devices (P = .92). Subjects rated the NNH device equivalent in
      ease of use to the Cook IO needle but slightly lower in perceived safety to the
      user. CONCLUSIONS: After training, all subjects successfully inserted the NNH IO
      device in a simulation environment, and most rated it as easy to use and safe.
      The NNH is a significant advance because IO needles are often not available in
      emergency departments in developing countries. Further studies are needed to
      evaluate clinical effectiveness of the NNH.

PMID- 22595585
TI  - Increased use of enoxaparin in pediatric trauma patients.
AB  - PURPOSE: Venous thromboembolism (VTE) in pediatric trauma patients has been
      reported from 0.7 to 4.2 patients per 1000 admissions. There are no clear
      guidelines for prophylactic anticoagulation in children. The purpose of this
      study was to examine the use of enoxaparin in pediatric trauma patients. METHODS:
      The Pediatric Health Information System database was queried from 2001 to 2008
      for patients 0 to 18 years with a primary diagnosis of trauma based on
      International Classification of Diseases, Ninth Revision, codes. Patients who
      received enoxaparin and/or diagnosed with VTE were identified using pharmacy and
      International Classification of Diseases, Ninth Revision, codes. Logistic
      regression was used to identify patient and hospital characteristics associated
      with VTE and enoxaparin use. RESULTS: Among 260,078 pediatric trauma patients,
      3195 were prescribed enoxaparin (1.23%), 2915 (1.12%) of whom were given
      enoxaparin without a diagnosis of VTE. The incidence of VTE remained stable
      (0.23%-0.28%), whereas the use of enoxaparin increased (0.75%-1.54%), especially
      in patients without VTE (0.65%-1.43%). Venous thromboembolism was significantly
      associated with pelvic fractures, intensive care unit stay, and central venous
      catheters (P = .017, P < .001, P < .001). CONCLUSIONS: Despite a stable VTE
      incidence, the use of enoxaparin significantly increased in pediatric trauma
      patients, suggesting that use of pharmacologic thromboprophylaxis is increasing
      in pediatric trauma centers.

PMID- 22595586
TI  - Reduction of radiation exposure in pediatric patients with trauma: cephalic
      stabilization improves adequacy of lateral cervical spine radiographs.
AB  - INTRODUCTION: Plain radiographs continue to play a role in cervical spine
      clearance. Inadequate radiographs commonly necessitate repeat x-rays or computed
      tomography imaging (10 * radiation dose). We have used the technique of cephalic
      stabilization (CS) to improve the results of plain radiographs. Cephalic
      stabilization lateral radiographs are obtained, with one assistant applying
      traction to the arms while another placing fingers in the patient's ears and
      stabilizing the head. This study tests the hypothesis that CS improves
      visualization of the cervicothoracic junction during lateral cervical spine
      radiographs. METHODS: A 2-year review of institutional pediatric trauma registry
      identified 46 patients with CS, matched 1:3 with controls. Randomized lateral
      radiographs were evaluated independently by 2 pediatric radiologists to determine
      adequate visualization of the craniocervical and cervicothoracic junctions.
      Reviewers were blinded to CS through image cropping. RESULTS: The proportion of
      adequate visualization of the cervicothoracic junction was 0.85 for cases with
      stabilization and 0.60 for controls. Odds of obtaining adequate visualization
      with stabilization are 3.8 times those without stabilization (P = .001) and were
      even greater for patients younger than 13 years. CONCLUSIONS: Cephalic
      stabilization improves visualization of the cervicothoracic junction in lateral
      cervical spine radiographs and can reduce radiation exposure in patients who
      would otherwise require further imaging.

PMID- 22595587
TI  - Television-related injuries in children--the British Columbia experience.
AB  - PURPOSE: In Canada, mortality from falling televisions (TVs) is the 15th leading
      cause of childhood death owing to injury. Frequency, characteristics, and
      outcomes of TV childhood injuries were examined to determine any at risk
      populations. METHODS: All TV-related traumas at a tertiary children's hospital
      from 1997 to 2011 were identified using the Canadian Hospitals Injury Reporting
      and Prevention Program database and the hospital's trauma database. Charts of
      admitted patients were reviewed. RESULTS: Analysis of 179 injuries (10-24 per
      year) revealed a high frequency of injury in the home and a preponderance of head
      and neck injuries. Toddlers were the most commonly injured age group. Eleven
      admitted patients were identified; 6 were admitted to intensive care unit with
      significant head injuries, 2 of whom required surgery. More than half of admitted
      patients were First Nations or recent immigrants. The length of stay for a ward
      vs intensive care unit admission was 1.3 days (range, <1-2 days) compared with
      7.6 days (range, <1-20 days), respectively. One child had residual deficits
      requiring rehabilitation, but there were no mortalities. CONCLUSION: Injury
      severity appeared higher in patients from First Nations and recent immigrant
      families. Television injury would likely have been prevented by a securing device
      or support.

PMID- 22595588
TI  - Vinyl glove ingestion in children: a word of caution.
AB  - BACKGROUND: Vinyl gloves when ingested will harden and develop sharp edges
      producing gastric bezoars; bowel obstruction; and, ultimately, perforation. We
      report 4 children with complications secondary to vinyl glove ingestion who
      required surgical intervention. METHODS: A 3-year-old boy, a 13-year-old
      adolescent girl with Down syndrome, a 14-year-old adolescent girl, and a 15-year
      old adolescent boy presented with bowel obstruction secondary to a bezoar caused
      by a vinyl glove. The adolescent girl with Down syndrome presented again at age
      17 years with a large vinyl glove gastric bezoar. Three of the children had
      mental retardation, and 1 was a victim of child abuse. Three had laparoscopic
      assisted removal of the vinyl glove bezoar, and 1 had laparotomy. RESULTS: The 4
      children recovered uneventfully. Two of the patients had unsuspected intestinal
      perforation. The caretakers denied awareness of the vinyl glove ingestion.
      CONCLUSIONS: Vinyl glove ingestion can cause intestinal obstruction and
      perforation. Vinyl gloves should be removed from the immediate proximity of
      mentally retarded patients or patients with pica. Most of the time, the finding
      of vinyl gloves as etiology of the obstruction or perforation is incidental. If
      the event is known or witnessed, prompt surgical intervention is generally
      recommended.

PMID- 22595589
TI  - Feasibility of conducting a prospective cohort study in pediatric surgery:
      introducing the Caregiver Quality of Life of pediatric patients referred for
      feeding tube insertion (CARE) study.
AB  - INTRODUCTION: High-quality prospective cohort studies are needed to answer
      research questions focused on prognosis. To determine the feasibility of
      conducting this type of research, a prospective cohort study focused on
      investigating health-related quality of life (HRQoL) of caregivers of children
      who require a gastrostomy (G) tube at the McMaster Children's Hospital was
      piloted from November 2009 to May 2011. METHODS: Recruitment began after research
      ethics board approval. Feasibility data were collected on all caregivers of
      patients assessed for G tube placement by a pediatric surgeon including
      recruitment status, protocol compliance, and HRQoL. Data were collected at 1
      month and 2 weeks before surgery and 2 weeks and 3, 6, 9, and 12 months after
      surgery. Health-related quality of life measures included the Short Form 36v2,
      the Caregiver Strain Index, and the Parent Experience of Childhood Illness.
      RESULTS: A total of 117 G procedures were conducted, and 39 caregivers met
      eligibility criteria. Thirty-one caregivers were enrolled (79.5% recruitment
      rate), 8 parents were not interested, and 26 were missed. Protocol adherence to
      the follow-up schedule is high (91.3%). CONCLUSION: Conducting high-level
      research with long-term follow-up in pediatric surgery is challenging. Factors
      including low prevalence of patients and competing priorities for busy clinicians
      indicate that multicenter collaboration is essential to research success in this
      field.

PMID- 22595591
TI  - Congenital absence of cartilaginous tracheal rings associated with esophageal
      atresia and trifurcated carina: a novel anomaly?
AB  - Tracheomalacia associated with esophageal atresia (EA) is a well-known condition.
      However, complete absence of tracheal rings (TRs) is extremely rare. Our aim is
      to describe a novel triad of conditions and to discuss the best treatment. An
      expremature male operated for EA presented with severe respiratory distress. The
      diagnosis of absent cartilage rings, suspected on bronchoscopy, was confirmed by
      optical coherence tomography. The absence of TRs was localized to a short
      tracheal segment, and the carina trifurcated into right upper lobe, right
      intermediate, and left main bronchus. The patient was treated with resection and
      anastomosis with a completely satisfactory course. Absence of TRs was previously
      reported by us in 2 other cases, both with associated EA and trifurcation of the
      carina. One child was treated with tracheostomy and the other with a stent, but
      the outcome was far from optimal. The patient with tracheostomy eventually
      underwent resection and anastomosis with tracheostomy closure. Congenital absence
      of TRs is extremely rare. Although localized, it is responsible for severe
      symptoms owing to complete tracheal collapse and may be misdiagnosed as
      tracheomalacia. In our experience, it has been associated with EA and trifurcated
      carina. Our limited experience suggests resection of the abnormal segment and
      tracheal anastomosis as the best treatment.

PMID- 22595592
TI  - Pseudoaneurysm of the radial branch of the splenic artery with pancreatic
      pseudocyst in a child with recurrent acute pancreatitis: treatment with
      endovascular stent graft and cystogastrostomy.
AB  - Splenic artery pseudoaneurysms (SAPs) are rare in children and usually follow
      abdominal trauma. Although pancreatitis is a well-known cause for SAP in adults,
      pancreatitis resulting in SAP has only sporadically been reported in children.
      Before the refinements of endovascular techniques for management of SAP, surgery
      used to be the mainstay of treatment, often resulting in splenectomy. Recent
      technical advancements, including development of smaller delivery systems and
      microcatheters, have made endovascular treatment feasible in children with SAP
      and increased chances of splenic preservation. In this article, we report a rare
      case of SAP associated with a pancreatic pseudocyst in a 5-year-old boy with
      recurrent acute pancreatitis that was managed by endovascular stent graft and
      cystogastrostomy.

PMID- 22595593
TI  - Life-threatening hemorrhage from a congenital hemangioma caused by birth trauma.
AB  - Pediatric surgeons frequently diagnose and treat vascular malformations. We
      present the case of a boy born with a large congenital hemangioma of the flank
      that ruptured during birth, resulting in life-threatening hemorrhage, requiring
      emergent excision. Prenatal diagnosis may help to identify such lesions, and
      pediatric surgeons must be ready to treat emergent complications of vascular
      malformations.

PMID- 22595594
TI  - Gastric adenomyoma mimicking gastric duplication cyst in a 5-year-old girl.
AB  - Gastric adenomyoma in children is a rare benign tumor composed of a mixture of
      duct-like epithelial structures with smooth muscle bundles. It has been
      considered as a subtype of ectopic pancreas because the epithelial component
      resembles that in pancreatic ducts. However, it is now recognized as an
      independent pathologic lesion. Gastric adenomyoma is usually asymptomatic but
      could cause obstruction, inflammation, ulceration, and malignant transformation.
      Hence, to achieve diagnostic certainty and to control symptoms, complete
      operative resection is recommended. To the best of our knowledge, this is the
      first case of gastric adenomyoma mimicking a gastric duplication cyst in
      children.

PMID- 22595595
TI  - Morio Kasai: a remarkable impact beyond the Kasai procedure.
AB  - Morio Kasai is one of the most influential Japanese pediatric surgeons. He is
      best recognized in the United States for his pioneering efforts in the field of
      biliary atresia. His work revolutionized the treatment of infants born with
      biliary atresia throughout the world. Less is known about his remarkable impact
      in the fields of general surgery and pediatric surgery. This review highlights
      some of Dr Kasai's major contributions and highlights the influence he had in the
      establishment of pediatric surgery as a field.

PMID- 22595596
TI  - Lipofibromatosis of the knee in a 19-month-old child.
AB  - Lipofibromatosis is a rare benign fibrofatty tumor of childhood. The typical
      presentation of this tumor is as a poorly demarcated and slow-growing mass
      involving the subcutaneous or deep soft tissues. Lipofibromatosis was first
      described in 2000, and since then, a small number of cases have been reported in
      the literature. We report a case of a 19-month-old boy who presented with a
      swelling of the anterior aspect of the right knee since birth, which had
      increased in size out of proportion with his growth. Magnetic resonance imaging
      was extremely useful because it showed the lipomatous nature of the mass,
      narrowing the differential diagnosis to the pediatric fibrofatty soft tissue
      tumors. The histologic biopsy revealed the specific diagnosis of
      lipofibromatosis. We describe the radiologic and pathologic features of this
      entity and discuss the differential diagnosis in a young child with a fat
      containing limb mass.

PMID- 22595597
TI  - Glandular resection and central embedding in hypospadias repair--a novel
      modification of the Barcat technique.
AB  - PURPOSE: Urethrocutaneous fistula and urethral or meatal stricture, to date,
      remain the commonest complications of hypospadias repair, with increased tissue
      tension being a major cause of failure. We developed a novel technique comprising
      glandular resection and central embedding of the neourethra to specifically
      address this critical issue. We report the results of the first 112 procedures,
      of which 7 cases were a secondary hypospadias repair. MATERIALS AND METHODS: All
      patients who underwent hypospadias repair using the glandular resection and
      central embedding technique over a period of 10 years were included into this
      retrospective single-surgeon case series. An independent third-party observer
      carried out follow-up examinations including urometric evaluation. RESULTS: The
      median follow-up was 37 months (range, 7-147 months). In the group of primary
      hypospadias repair, urethrocutaneous fistulas were observed in 4%, all requiring
      surgical revision, and meatal or urethral stricture were observed in 4% of the
      patients, treated either surgically or by dilatation. In 98% of the patients, the
      neomeatus was located at the tip of the glans. A cosmetically impeccable slitlike
      appearance of the meatus was achieved in 84%, and a cosmetically acceptable oval
      shape was achieved in 10% of the patients. Both maximum and average urinary flow
      rates were within the standard ranges for the respective age groups in 93.7% and
      96%, respectively. There was no significant residual urine in 92% of the
      patients. In the group of secondary hypospadias repairs, both cosmetic and
      functional results were similar, and no complications were noted. CONCLUSIONS:
      Glandular resection and central embedding is a promising expansion of the
      repertoire of Barcat modifications. It allows safe embedding of the neourethra
      and glandular closure without detrimental tension. The cosmetic and functional
      results are encouraging.

PMID- 22595598
TI  - Tapering duodenoplasty and gastrojejunostomy in the management of idiopathic
      megaduodenum in children.
AB  - PURPOSE: The purpose of this study is to present the management of idiopathic
      megaduodenum in children. METHODS: A retrospective analysis of 4 cases of
      megaduodenum admitted from 2005 to 2011 was performed evaluating clinical
      features, radiologic data, treatment, pathologic findings, and prognosis. The
      corresponding literature was reviewed. RESULTS: The diagnosis of nonobstructive
      megaduodenum was confirmed by upper gastrointestinal contrast study,
      ultrasonography, and exploratory laparotomy. Treatment consisted of either
      tapering duodenoplasty with pylorus division and closure of the proximal stump
      plus Roux-en-Y gastrojejunostomy or tapering duodenoplasty with closure of the
      proximal stump and end-to-side gastrojejunostomy. On pathologic evaluation,
      neural and vascular structures appeared normal in all sections. All symptoms,
      including diarrhea, bloating, vomiting, and nausea, had resolved on follow-up,
      and all patients experienced rapid weight gain after their operation.
      CONCLUSIONS: Idiopathic megaduodenum without organic obstruction is a rare
      clinical condition. Massive dilatation confined to the duodenum was shown by
      upper gastrointestinal contrast studies and ultrasonography and can also be
      identified on antenatal ultrasonography. In children with megaduodenum,
      satisfactory results can be obtained by tapering duodenoplasty with proximal
      stump closure and gastrojejunostomy with either Roux-en-Y or end-to-side
      anastomosis.

PMID- 22595600
TI  - Re: Complete urogenital nonunion.

PMID- 22595601
TI  - Single-balloon enteroscopy-assisted endoscopic retrograde
      cholangiopancreatography for treatment of cholangitis in a patient with a Kasai
      portoenterostomy.
AB  - Primary therapy for biliary atresia is a surgical hepatoportoenterostomy (Kasai
      procedure), which has been shown to reduce mortality, but is frequently
      complicated by ascending cholangitis and the development of biliary cirrhosis.
      Previously reported therapy for recurrent cholangitis caused by biliary
      obstruction has included surgical revision and percutaneous biliary drainage, but
      endoscopic retrograde cholangiopancreatography has not been previously described.
      Here, we report a patient with recurrent cholangitis after a Kasai procedure and
      an anastomotic stricture successfully treated with single-balloon enteroscopy
      assisted endoscopic retrograde cholangiopancreatography. This novel technique
      could be considered in patients with this common complication of the Kasai
      procedure and may impact long-term outcomes in this patient population.

PMID- 22595602
TI  - Early laparoscopic repair for blunt duodenal perforation in an adolescent.
AB  - Duodenal perforation secondary to blunt abdominal trauma in children is rare and
      usually associated with delays in diagnosis and surgical intervention. The
      authors encountered such a case in a 12-year-old boy owing to his falling over
      the handlebar of a bicycle. Imaging examination showed that there was a
      perforation over the fourth portion of the duodenum without concomitant injuries.
      Using a 5-port transperitoneal laparoscopic technique, primary closure of the
      perforation was successfully performed at 6 hours after the impact. Laparoscopic
      approach appears to be safe and feasible in hemodynamically stable children with
      solitary traumatic duodenal perforation if the operation can be performed early
      in the course of the incident.

PMID- 22595603
TI  - Gastrointestinal stromal tumor: a very rare cause of jejunoileal intussusception
      in a 6-year-old girl.
AB  - A 6-year-old girl was admitted to the emergency department with abdominal pain
      and bilious vomiting of 3 days in duration. Abdominal ultrasound examination
      showed an 8-cm-long intussuscepted intestinal segment with a target sign. There
      was a 26 * 28 * 23 mm nonperistaltic anechoic cystic mass suggestive of a
      duplication cyst. At laparotomy, the ileocecal region was normal with many
      enlarged lymph nodes from which biopsies were taken. There was a 20-cm-long
      intussuscepted segment at the proximal ileum close to the jejunum. After manual
      reduction, a 2-cm-long edematous segment resembling a duplication cyst served as
      the lead point. The segment was excised, and a primary bowel anastomosis was
      performed. She was discharged on the fifth postoperative day. The histopathologic
      examination revealed that the excised segment contained a gastrointestinal
      stromal tumor measuring 2.5 cm, with a mitotic rate of 2 to 3 mitoses per 50 high
      power fields (low-risk group) showing an infiltrative growth pattern. On
      immunohistochemistry assay, some of the tumor cells were CD117 and CD34 positive,
      whereas all of them were smooth muscle actin and S-100 positive but CD10
      negative. Staining index with Ki-67 was 5%. Surgical margins were free of tumor.
      The lymph nodes showed reactive hyperplasia. She was referred to the pediatric
      oncology department for further evaluation. Gastrointestinal stromal tumors are
      common in adults and may lead to intussusception. To the best of our knowledge,
      this is the first childhood case of gastrointestinal stromal tumor causing
      jejunoileal intussusception in the literature.

PMID- 22595604
TI  - Reduction en masse in a 7-year-old boy: an interesting case.
AB  - Reduction en masse is a complication of inguinal hernia reduction in which a
      hernia is reduced back into the peritoneal cavity, but a loop of bowel remains
      trapped inside the hernia sac after reduction. Reduction en masse can be
      difficult to diagnose because of generalized and nonspecific symptoms. We
      describe a 7-year-old boy with an atypical presentation of reduction en masse
      after hernia reduction. The patient was a previously healthy child who presented
      with a mildly painful right inguinal mass of 1 day duration. An incarcerated
      hernia was noted, and after reduction, the pain dissipated for a short period,
      only to return with pain in the right lower quadrant and generalized peritoneal
      irritation. At surgical exploration, a reduction en masse was definitively
      diagnosed, and the incarcerated bowel was released from the hernia sac.

PMID- 22595605
TI  - Successful use of extracorporeal membrane oxygenation for acute respiratory
      failure in a patient with chronic granulomatous disease.
AB  - A 9-year-old boy presented with pneumonia, bilateral pulmonary lesions, and
      fulminant respiratory failure requiring support with extracorporeal membrane
      oxygenation (ECMO). Open lung biopsy and subsequent bronchoscopy identified
      Nocardia cyriacigeorgica and Burkholderia cepacia pneumonia. Chronic
      granulomatous disease (CGD) was diagnosed by an abnormal neutrophil oxidative
      burst assay. An aggressive diagnostic and therapeutic strategy, which included
      ECMO, allowed for patient survival and return to baseline function. No ECMO
      survivors with CGD have previously been reported. It is now recognized that
      several forms of CGD exist, and some forms may be compatible with long-term
      survival. Therefore, the diagnosis of CGD should not necessarily be considered a
      contraindication to ECMO. This is the first known survivor of CGD-related acute
      respiratory failure supported by ECMO.

PMID- 22595606
TI  - Type 2 Abernethy malformation presenting as a portal vein-coronary sinus fistula.
AB  - We report the case of a child with Abernethy malformation with an anomalous
      connection between the portal vein and the coronary sinus. After 30 months of
      close follow-up, the patient developed hepatoblastoma, a previously documented
      complication of the Abernethy malformation. This case reports a unique variant of
      Abernethy malformation and documents the first reported case of hepatoblastoma in
      a patient with type 2 Abernethy malformation.

PMID- 22595607
TI  - Post meningocele repair urinary ascites in a neonate--a rare presentation.
AB  - A full-term female neonate with a large lumbosacral meningocele developed sudden
      abdominal distension and urinary retention after meningocele repair. An erect
      abdominal radiograph showed homogeneously opacified areas with a paucity of
      intestinal gas. Abdominal ultrasound revealed ascites with multiple internal
      echoes. With a provisional diagnosis of hollow viscus perforation, an emergency
      laparotomy was performed, which failed to reveal any leak from the urinary tract.
      However, fluid analysis confirmed the diagnosis of urinary ascites. The patient
      developed repeated episodes of urinary retention after catheter removal. She was
      started on clean intermittent catheterization (CIC) to ensure adequate bladder
      drainage. At 6 months of follow-up, ultrasound of the urinary tract, voiding
      cystourethrogram, and magnetic resonance imaging of the spine were all within
      normal limits. The CIC was discontinued, and the patient was observed. At
      present, she is voiding normally with a good stream. Failure to establish normal
      micturition after meningocele repair and CIC requirements suggested a neurogenic
      cause. Bladder rupture, secondary to spinal shock resulting in bladder atonia,
      could not be ruled out. The perforation (leading to urinary ascites) could be
      owing to bladder atonia and spinal shock rather than detrusor sphincter
      dyssynergia.

PMID- 22595608
TI  - Complex communicating bronchopulmonary foregut malformation with pancreatic
      heterotopy depicted with fetal magnetic resonance imaging: a case report.
AB  - Bronchopulmonary foregut malformation (BPFM) is a group of rare congenital
      anomalies that affect the respiratory and upper gastrointestinal tracts. We
      report here the first case of prenatal depiction of communicating BPFM, including
      extrapulmonary sequestration and foregut cyst, both with pancreatic
      differentiation. Magnetic resonance imaging on the fetus confirmed a
      polymalformative syndrome with right-lung and gastric cysts and allowed the
      detection of respiratory and alimentary tracts communication and aberrant feeding
      vessels. Diagnosis was confirmed after birth by multidetector computed tomography
      and postnatal pathologic findings. The patient, a boy, underwent surgery for
      respiratory distress at 4 weeks of life. This singular case confirms the benefits
      of early surgery for communicating BPFM.

PMID- 22595609
TI  - Molecular pathways: targeting p21-activated kinase 1 signaling in cancer-
      opportunities, challenges, and limitations.
AB  - The evolution of cancer cells involves deregulation of highly regulated
      fundamental pathways that are central to normal cellular architecture and
      functions. p21-activated kinase 1 (PAK1) was initially identified as a downstream
      effector of the GTPases Rac and Cdc42. Subsequent studies uncovered a variety of
      new functions for this kinase in growth factor and steroid receptor signaling,
      cytoskeleton remodeling, cell survival, oncogenic transformation, and gene
      transcription, largely through systematic discovery of its direct,
      physiologically relevant substrates. PAK1 is widely upregulated in several human
      cancers, such as hormone-dependent cancer, and is intimately linked to tumor
      progression and therapeutic resistance. These exciting developments combined with
      the kinase-independent role of PAK1-centered phenotypic signaling in cancer cells
      elevated PAK1 as an attractive drug target. Structural and biochemical studies
      revealed the precise mechanism of PAK1 activation, offering the possibility to
      develop PAK1-targeted cancer therapeutic approaches. In addition, emerging
      reports suggest the potential of PAK1 and its specific phosphorylated substrates
      as cancer prognostic markers. Here, we summarize recent findings about the PAK1
      molecular pathways in human cancer and discuss the current status of PAK1
      targeted anticancer therapies.

PMID- 22595610
TI  - Identification of genetic recombination between Acinetobacter species based on
      multilocus sequence analysis.
AB  - During multilocus sequence analysis of Acinetobacter calcoaceticus-Acinetobacter
      baumannii complex, we identified the evidence of recent genetic recombination
      between 2 Acinetobacter species. While 3 isolates belonged to A. nosocomialis
      based on 16S rRNA, gyrB, fusA, gdhB, and rplB gene sequences, they showed close
      relationships with Acinetobacter genomic species 'close to 13TU' in rpoB, recA,
      cpn60, rpoD, and gltA gene trees.

PMID- 22595611
TI  - Educating tomorrow's clinical researchers: a review of research preparation in
      undergraduate education.
AB  - BACKGROUND: One large health region in England was experiencing difficulties in
      recruiting to clinical research posts which required registered nurse or allied
      health professional skills. OBJECTIVES: Pre-registration preparation may
      influence practitioners' career choices and the study reviewed the research
      content in pre-registration nurse/AHP degree level programmes in the region to i)
      describe key features of the modules, and ii) determine the extent to which
      clinical research featured. DESIGN AND SETTINGS: There are eight universities in
      the region. We reviewed and analysed 46 research and evidence-based practice
      module guides from relevant pre-registration degree level programmes. Documentary
      analysis was used and the findings were reviewed by the project group. RESULTS:
      Modules aimed to produce practitioners who were aware of the principles of
      evidence based practice, and who could locate and evaluate research findings.
      There was some exposure to clinical research, though this was largely indirect,
      through considering research findings. Therapy students were more likely than
      nursing students to conduct a small clinical study for their final year
      assignment. CONCLUSIONS: Pre-registration programmes focused on producing
      practitioners who were competent users of research evidence to inform practice,
      rather than clinical researchers, and this was inevitably the focus of the
      research modules. However, feasible opportunities for increasing students'
      exposure to clinical research were identified.

PMID- 22595612
TI  - Factors influencing nursing students' academic and clinical performance and
      attrition: an integrative literature review.
AB  - Predicted workforce shortages have resulted in government initiatives to increase
      student numbers in preregistration nursing education. In tandem schools of
      nursing need to ensure students' progress and complete. The aim of this review
      was to identify factors that influence preregistration nursing students' academic
      performance, clinical performance and attrition. An integrative review of both
      quantitative and qualitative literature was conducted using validated appraisal
      checklists. The review included studies published from 1999 to 2011 in the
      databases: MEDLINE, CINAHL, Proquest nursing, Proquest Education (via Proquest
      5000), ERIC, Journals@Ovid, PsychINFO and ScienceDirect. Studies were categorised
      according to their impact on academic progression, clinical progression and
      attrition. Forty four studies were found; most used quantitative methodologies.
      The review identified that few studies explored factors that impact on students'
      clinical performance. The four categories that potentially impact on nursing
      students' academic performance and attrition were: demographic, academic,
      cognitive and personality/behavioural factors. The challenge for universities
      committed to students' success is to develop strategies aimed at addressing these
      factors that are appropriate to specific contexts and student cohorts.

PMID- 22595613
TI  - How do nurses solve drug calculation problems?
AB  - This article reports on a pilot study that examined the cognitive processes and
      strategies used by senior nurses to solve written drug calculation problems.
      METHODOLOGY: Verbal protocol methodology was used to gain and analyse data from
      eight senior nurses now working in the education setting. The data was analysed
      using verbal protocol analysis. RESULTS: Nurses used a range of strategies to
      solve the problems, not just the nursing formula. The cognitive processes of the
      nurses showed a larger number of steps devoted to problem representation and only
      a few steps devoted to actually solving the problem. CONCLUSION: Nurse educators
      need to consider the importance of problem representation in solving drug
      calculations and in particular ensure that written questions are representative
      of clinical practice.

PMID- 22595615
TI  - A new cell-based method for assessing the eye irritation potential of chemicals:
      an alternative to the Draize test.
AB  - Using a human corneal cell line (HCE-T cells) and 2 evaluation criteria, we
      developed a new alternative method to assess the eye irritation potential of
      chemicals. We exposed HCE-T cells to different concentrations of 38 chemicals for
      1h and measured relative cell viability (RCV) as an endpoint at each
      concentration. Using the RCV values, we calculated the RCV50. We also exposed HCE
      T cells to 3 fixed concentrations of the 38 chemicals (5%, 0.5%, and 0.05%) for
      1h and measured the RCV at each concentration. Using the RCV values at 5%, 0.5%,
      and 0.05%, we developed a new criterion for eye irritation potential (total eye
      irritation score, TEIS) and estimated the ocular irritancy. We then assessed the
      correlation of the results of RCV50 and TEIS with those of the Draize rabbit eye
      irritation. Both the RCV50 and TEIS results exhibited good positive correlations
      (sensitivity: 80.77%, specificity: 83.33%, and accuracy: 81.58% for TEIS;
      sensitivity: 73.08-76.92%, specificity: 75.00%, and accuracy: 73.68-76.32% for
      RCV50). We conclude that the new in vitro model using HCE-T cells is a good
      alternative evaluation model for the prediction of the eye irritation potential
      of chemicals.

PMID- 22595614
TI  - Role of mammary epithelial and stromal P450 enzymes in the clearance and
      metabolic activation of 7,12-dimethylbenz(a)anthracene in mice.
AB  - Microsomal cytochrome P450 (P450) enzymes, which are important in the metabolism
      of carcinogens, are expressed in both epithelial and stromal cells in the mammary
      gland. The aim of this study was to investigate the roles of mammary epithelial
      P450 enzymes in the bioactivation and disposition of 7,12
      dimethylbenz(a)anthracene (DMBA), a breast carcinogen, in the mammary gland. A
      new mouse model (named MEpi-Cpr-null) was produced, wherein P450 activities in
      the mammary epithelial cells are suppressed through tissue-specific deletion of
      the gene for P450 reductase (Cpr), an enzyme required for the activities of all
      microsomal P450 enzymes. Comparisons between wild-type and MEpi-Cpr-null mice
      showed that the tissue-specific deletion of Cpr in the mammary epithelial cells
      was accompanied by significant increases in the levels of DMBA and DMBA-DNA
      adduct in the mammary gland following a single intraperitoneal injection of DMBA
      at 50mg/kg. Immunohistochemical and immunoblot analysis further revealed greater
      induction of CYP1B1 expression by the DMBA treatment in the mammary stroma of the
      MEpi-Cpr-null mice than in that of the WT mice. These findings not only
      demonstrate that the epithelial P450 enzymes play important roles in the
      clearance of DMBA, but also suggest that P450 enzymes in both mammary epithelial
      and stromal cells contribute to carcinogen-mediated DNA damage.

PMID- 22595616
TI  - The role of iron in neurodegeneration--Mossbauer spectroscopy, electron
      microscopy, enzyme-linked immunosorbent assay and neuroimaging studies.
AB  - The possible role of iron in neurodegeneration was studied by various techniques:
      electron microscopy, enzyme-linked immunosorbent assay, Mossbauer spectroscopy,
      atomic absorption, ultrasonography and magnetic resonance imaging. The
      measurements were made on human tissues extracted from liver and from brain
      structures involved in diseases of the human brain: substantia nigra
      (Parkinson's, PD), hippocampal cortex (Alzheimer's, AD) and globus pallidus
      (progressive supranuclear palsy, PSP). The sizes of the iron cores of ferritin,
      the main iron storage compound in tissues, were found to be smaller in brain than
      in liver. Brain ferritin has a higher proportion of H to L chains compared to
      liver. A significant decrease of the concentration of L chains in PD compared to
      control was found. No increase in the concentration of iron in PD versus control
      was detected; however, there was an increase of labile iron, which constitutes
      only 20/00 of brain iron. In AD an increase in the concentration of ferritin was
      noticed, without a significant increase in iron concentration. In PSP an increase
      of total iron was observed. Our findings suggest that the mechanisms leading to
      the death of nerve cells in these three diseases may be different, although all
      may be related to iron mediated oxidative stress.

PMID- 22595617
TI  - No higher risk for colorectal cancer in atrophic gastritis-related
      hypergastrinemia.
AB  - BACKGROUND: Atrophic gastritis of the corporal mucosa is a frequent cause of
      hypergastrinemia. Hypergastrinemia is implicated in colorectal cancer
      development. AIM: To assess whether hypergastrinemic atrophic gastritis is
      associated with a higher risk of neoplastic colorectal lesions. METHODS: Among
      441 hypergastrinemic atrophic gastritis patients, 160 who were aged >40 and
      underwent colonoscopy for anaemia, diarrhoea or colorectal cancer-screening were
      retrospectively selected. Each patient was age- and gender-matched with a
      normogastrinemic control with healthy stomach. Controls had colonoscopy,
      gastroscopy with biopsies and gastrin assessment. RESULTS: 160 hypergastrinemic
      atrophic gastritis patients and 160 controls were included. 28 atrophic gastritis
      patients and 36 controls had neoplastic colorectal lesions (p=0.33). Patients and
      controls did not differ for frequency of colorectal adenomas (10.6% vs. 13.1%,
      p=0.60) or cancer (6.9% vs. 9.4%, p=0.54). Hypergastrinemic atrophic gastritis
      was not associated with a higher probability of developing colorectal cancer (OR
      1.03, 95% CI 0.34-3.16). Age >50 years (OR 3.86) but not hypergastrinemia (OR
      0.61) was associated with colorectal cancer. CONCLUSIONS: Hypergastrinemic
      atrophic gastritis is not associated with higher risk for colorectal cancer.
      Atrophic gastritis-related hypergastrinemia is not associated with an increased
      risk of neoplastic colorectal lesions. Closer surveillance of colonic neoplasia
      in atrophic gastritis patients seems not appropriate.

PMID- 22595618
TI  - Genetic predisposition and increasing dietary fructose exposure: the perfect
      storm for fatty liver disease in Hispanics in the U.S.

PMID- 22595619
TI  - Sad and happy facial emotion recognition impairment in progressive supranuclear
      palsy in comparison with Parkinson's disease.
AB  - The severity of motor and non-motor symptoms of progressive supranuclear palsy
      (PSP) has a profound impact on social interactions of affected individuals and
      may, consequently, contribute to alter emotion recognition. Here we investigated
      facial emotion recognition impairment in PSP with respect to Parkinson's disease
      (PD), with the primary aim of outlining the differences between the two
      disorders. Moreover, we applied an intensity-dependent paradigm to examine the
      different threshold of encoding emotional faces in PSP and PD. The Penn emotion
      recognition test (PERT) was used to assess facial emotion recognition ability in
      PSP and PD patients. The 2 groups were matched for age, disease duration, global
      cognition, depression, anxiety, and daily L-Dopa intake. PSP patients displayed
      significantly lower recognition of sad and happy emotional faces with respect to
      PD ones. This applied to global recognition, as well as to low-intensity and high
      intensity facial emotion recognition. These results indicate specific impairment
      of recognition of sad and happy facial emotions in PSP with respect to PD
      patients. The differences may depend upon diverse involvement of cortical
      subcortical loops integrating emotional states and cognition between the two
      conditions, and might represent a neuropsychological correlate of the apathetic
      syndrome frequently encountered in PSP.

PMID- 22595620
TI  - Gaba and serotonin molecular neuroimaging in essential tremor: a clinical
      correlation study.
AB  - BACKGROUND: Essential tremor is the most common movement disorder in adults, but
      its exact etiology and pathophysiology are still not fully understood. There is
      some consensus, however, about the involvement of the cerebellum and accumulating
      evidence points towards a dysfunction of the gabaergic system. We hypothesize
      that the serotonin neurotransmission system may also play a role as it does in
      tremor in Parkinson disease. This study aimed to investigate the association
      between the severity of tremor symptoms and the gabaergic and serotoninergic
      neurotransmission systems in essential tremor. MATERIAL AND METHODS: We measured
      the tremor clinical rating scale score and acquired DASB and Flumazenil PET scans
      in 10 patients who presented with essential tremor at different stages of
      clinical severity. Statistically significant correlations were sought between the
      scale scores and parametric binding potential images. RESULTS: The correlation
      analysis of cerebellar Flumazenil uptake and tremor clinical rating scale scores
      reached statistical significance (R2 = 0.423, p = 0.041), whereas no association
      was detected in the DASB scans. CONCLUSIONS: The severity of tremor correlated
      with the abnormalities found in GABA receptor binding, suggesting a primary
      gabaergic deficiency or a functional abnormality at the level of GABA(A) receptor
      subtypes. These results may assist in the rational development of new
      pharmacological treatments for essential tremor.

PMID- 22595621
TI  - Grey matter volume correlates of cerebrospinal markers of Alzheimer-pathology in
      Parkinson's disease and related dementia.
AB  - Regional brain grey matter volume (GMV) reductions and abnormal cerebrospinal
      fluid (CSF) levels of tau and Abeta, extensively studied as biomarkers of
      Alzheimer's disease (AD), have also been reported in Parkinson's disease (PD) and
      related dementia (PDD). However, the relationship between these CSF and MRI
      biomarkers in PD and PDD remains unexplored. We studied these associations in 33
      PD patients (18 with no dementia [PDND]; 15 fulfilling PDD criteria) and 12
      neurologically unimpaired controls, with neuropsychological assessment, CSF ELISA
      studies, and voxel-based morphometry (VBM) analysis of high-field brain MRI.
      Neuropsychological assessment showed a gradation in cognitive performance from
      controls to PDND (significantly worse on visuospatial performance) and then to
      PDD (more impaired on memory, naming, fluency and visuospatial functions). No CSF
      VBM correlations were found in controls or PDND patients. In contrast, in the
      analysis of both the PDD subgroup and the entire PD (PDND + PDD) sample, we found
      significant negative CSF-GMV correlations for tau and phospho-tau and significant
      positive CSF-GMV correlations for Abeta in mostly frontal and temporal
      structures. The correlations in the entire PD sample fitted with a linear model
      and were thus unlikely to have been driven solely by the PDD subgroup.
      Additionally, an association between both the CSF markers and the CSF-associated
      GMV reductions with several neuropsychological functions was found. We interpret
      that CSF markers of AD pathology are associated with VBM-measures of brain
      atrophy in PD-related dementia and within the PD cognitive continuum, and deserve
      further attention as putative biomarkers of cognitive impairment and dementia in
      PD.

PMID- 22595622
TI  - Effects of mechanical vibration on proliferation and osteogenic differentiation
      of human periodontal ligament stem cells.
AB  - OBJECTIVE: Paradental tissues (alveolar bone, periodontal ligament (PDL), and
      gingiva) have the capacity to adapt to their functional environment. The
      principal cellular elements of the PDL play an important role in normal function,
      regeneration of periodontal tissue and in orthodontic treatment. Recently,
      several studies have shown that low-magnitude, high-frequency (LMHF) mechanical
      vibration can positively influence bone homeostasis; however, the mechanism and
      optimal conditions for LMHF mechanical vibration have not been elucidated. It has
      been speculated that LMHF mechanical vibration stimulations have a favourable
      influence on osteocytes, osteoblasts and their precursors, thereby enhancing the
      expression of osteoblastic genes involved in bone formation and remodelling. The
      objective of this study was to test the effect of LMHF mechanical vibration on
      proliferation and osteogenic differentiation of human PDL stem cells (PDLSCs).
      METHODS: Human PDLSCs were isolated from premolar teeth and randomized into
      vibration (magnitude: 0.3g; frequency: 10-180 Hz; 30 min/24h) and static
      cultures. The effect of vibration on PDLSC proliferation, differentiation and
      osteogenic potential was assessed at the genetic and protein level. RESULTS:
      After LMHF mechanical vibration, PDLSC proliferation was decreased; however, this
      was accompanied by increased markers of osteogenesis in a frequency-dependent
      manner. Specifically, alkaline phosphatase activity gradually increased with the
      frequency of vibration, to a peak at 50 Hz, and the level of osteocalcin was
      significantly higher than control following vibration at 40 Hz, 50 Hz, 60 Hz, 90
      Hz and 120 Hz. Levels of Col-I, Runx2 and Osterix were significantly increased by
      LMHF mechanical vibration at frequencies of 40 Hz and 50 Hz. CONCLUSIONS: Our
      data demonstrates that LMHF mechanical vibration promotes PDLSC osteogenic
      differentiation and implies the existence of a frequency-dependent effect of
      vibration on determining PDLSC commitment to the osteoblast lineage.

PMID- 22595623
TI  - Influence of chronic alcoholism and oestrogen deficiency on the variation of
      stoichiometry of hydroxyapatite within alveolar bone crest of rats.
AB  - OBJECTIVE: Previous findings suggest that chronic alcoholism and oestrogenic
      deficiency may affect bones in general (including alveolar bone) and increase
      individuals' susceptibility to the development of periodontal disease. The aim of
      this study was to assess possible alterations in the chemical composition of
      alveolar bone in rats subjected to chronic alcoholism, oestrogen deficiency or
      both. DESIGN: Fifty-four rats were initially divided into two groups:
      ovariectomized (Ovx), and Sham operated (Sham). A month after surgery, the groups
      were sub-divided and received the following dietary intervention for eight weeks:
      20% alcohol, isocaloric diet and ad libitum diet. Samples of the mandible, in the
      alveolar bone crest region, were analyzed to verify possible changes in the
      stoichiometric composition of bone hydroxyapatite, by measuring the relationship
      between the concentration of calcium and phosphorus (Ca/P ratios), using micro X
      ray fluorescence spectrometry. RESULTS: The ad libitum groups presented the
      highest average values of Ca/P ratios, while the groups with dietary restrictions
      presented the smallest average values. The Ovx ad libitum group presented the
      highest values of Ca/P ratios (2.03 +/- 0.04). However, these values were not
      considered statistically different (p>0.05) from the Sham ad libitum group (2.01
      +/- 0.01). The Ovx alcohol group presented lower values for Ca/P ratios (1.92 +/-
      0.06), being the only group statistically different (p<0.001) from the Sham ad
      libitum group. Potential confounding variables are discussed. CONCLUSION:
      Ovariectomy associated with alcohol consumption at 20% significantly changed the
      stoichiometry composition of hydroxyapatite in the alveolar bone crest, leading
      to a reduction in Ca/P ratios.

PMID- 22595624
TI  - Variability in permanent tooth size of three ancient populations in Xi'an,
      northern China.
AB  - OBJECTIVES: This paper compares permanent dental dimensions between three ancient
      populations that belonged to the same biological population throughout a temporal
      range of 2000 years to detect temporal trends and metric variation in dentition.
      MATERIALS AND METHODS: The samples analysed were dental remains of 4502 permanent
      teeth from 321 individuals, which were excavated from three archaeological sites:
      Chang'an (1000-1300 years BP), Shanren (2200 years BP) and Shaolingyuan (3000
      years BP) in the Xi'an region (northern China). For each tooth three standard
      measurements were taken: Mesiodistal (MD) diameter of crown, labiolingual or
      buccolingual (BL) diameter of crown and length of root (LR). RESULTS: Three
      ancient population samples generally displayed the same dental dimensions
      (p>0.05), whereas some tooth types varied. The Shaolingyuan had larger canine and
      the smallest maxillary second molars and the Chang'an had the largest mandibular
      first molars in the MD dimension. The Shanren had the smallest maxillary third
      molars and mandibular central incisors, and the Chang'an had the smallest
      maxillary lateral incisors in the BL dimension. In the LR measures, statistically
      significant differences of five tooth types showed that the Chang'an were smaller
      than the Shaolingyuan and the Shanren. Comparisons of coefficients of variation
      for teeth showed that the length of root and third molar usually displayed
      greater variation. CONCLUSIONS: Decreasing or increasing trend for crown size
      does not occur between the ancient populations, while changes in crown size of a
      few tooth types fluctuate. The root size is more variable than the crown size and
      is likely to reflect a degenerated trend in a few tooth types.

PMID- 22595625
TI  - [Low dose ketamine for pediatric procedure-related pain].
AB  - For painful procedures in children, national recommendations are now available in
      France. When sedation-analgesia with nitrous oxide/oxygen mixture fails, in order
      to perform a painful procedure under good conditions, low dose ketamine (IV bolus
      titration 0.5 mg/kg but not more than 2 mg/kg) is the only drug potentially used
      by a trained physician, without the presence of an anaesthesiologist (Grade A).
      With these dosages without drug combination, the highest level of security
      depends largely on the quality of the hospital environment (Grade A).
      Intramuscular (<4 mg/kg) is an alternative route, but the recovery time is
      delayed (Grade B). The optimal management is performed by an anesthesiologist, it
      is necessary to facilitate access to the operating room for children undergoing
      this type of procedure (Professional consensus). Mainly IV ketamine can be used
      by pediatric intensive care and emergency physicians who currently have medical
      skills to detect and treat side effects.

PMID- 22595626
TI  - Multisociety (AATS, ACCF, SCAI, and STS) expert consensus statement: operator and
      institutional requirements for transcatheter valve repair and replacement, part
      1: transcatheter aortic valve replacement.

PMID- 22595627
TI  - Effect of benchmarking projects on outcomes of coronary artery bypass graft
      surgery: challenges and prospects regarding the quality improvement initiative.
AB  - OBJECTIVE: The Japan Cardiovascular Surgery Database (JCVSD) was established in
      2000 and initiated a benchmarking project to improve the quality of
      cardiovascular surgery. Although the importance of quality improvement
      initiatives has been emphasized, few studies have reported the effects on
      outcomes. METHODS: To examine the time-trend effects in initial JCVSD
      participants (n = 44), we identified 8224 isolated coronary artery bypass graft
      (CABG) procedures performed between 2004 and 2007. The impact of surgery year was
      examined using a multiple logistic regression model that set previously
      identified clinical risk factors and surgery year as fixed effects. To examine
      the difference in outcomes between initial participants (n = 44) and halfway
      participants (n = 55), we identified 3882 isolated CABG procedures performed in
      2007. The differences between the 2 hospital groups were examined using a
      multiple logistic regression model that set clinical risk factors, hospital
      procedure volume, and hospital groups as fixed effects. RESULTS: For operative
      mortality, the odds ratio of surgery year was 0.88 (P = .083). Observed/expected
      (OE) ratios for operative mortality were 0.71 in 2004, 0.73 in 2005, 0.63 in
      2006, and 0.54 in 2007. As for composite mortality and major morbidities
      (reoperation, stroke, dialysis, infection, and prolonged ventilation), odds ratio
      of surgery year was 0.97 (P = .361). OE ratios for composite mortality and
      morbidities were 1.01 in 2004, 1.04 in 2005, 1.04 in 2006, and 0.94 in 2007.
      Compared with halfway participants, initial participants had a significantly
      lower rate of operative mortality (odds ratio = 0.527; P = .008) and composite
      mortality and major morbidities (odds ratio 0.820; P = .047). CONCLUSIONS: This
      study demonstrated that a quality improvement initiative for cardiovascular
      surgery has positive impacts on risk-adjusted outcomes. Although the primary
      target of benchmarking was 30-day mortality in Japan, major morbidities were less
      affected by those activities.

PMID- 22595628
TI  - Dynamics of targeted cancer therapy.
AB  - Targeted cancer therapies offer renewed hope for an eventual 'cure for cancer'.
      At present, however, their success is often compromised by the emergence of
      resistant tumor cells. In many cancers, patients initially respond to single
      therapy treatment but relapse within months. Mathematical models of somatic
      evolution can predict and explain patterns in the success or failure of
      anticancer drugs. These models take into account the rate of cell division and
      death, the mutation rate, the size of the tumor, and the dynamics of tumor growth
      including density limitations caused by geometric and metabolic constraints. As
      more targeted therapies become available, mathematical modeling will provide an
      essential tool to inform the design of combination therapies that minimize the
      evolution of resistance.

PMID- 22595629
TI  - Hemorrhagic gastritis with dabigatran in a patient with renal insufficiency.
AB  - BACKGROUND: Dabigatran etexilate is the first oral direct thrombin inhibitor
      approved in the United States. Unlike warfarin, dabigatran has no known antidote.
      Providers should be aware of patients that may be at risk for dabigatran
      coagulopathies and recognize potential treatment options. OBJECTIVE: To report a
      case of hemorrhagic gastritis in a patient with chronic renal insufficiency
      recently initiated on dabigatran etexilate. CASE SUMMARY: An 85-year-old white
      man with a known history of hypertension and stage III chronic kidney disease
      presented to the Emergency Department complaining of dark stools, shortness of
      breath, and abdominal pain. The patient recently started dabigatran 150mg twice
      daily for new-onset atrial fibrillation. An upper gastrointestinal endoscopy
      identified non-specific gastritis with hemorrhage. It was determined to be
      probable using the Naranjo Probability Scale that gastrointestinal hemorrhaging
      was a result of dabigatran therapy. Fresh frozen plasma was used to reverse the
      dabigatran-induced coagulopathy. CONCLUSION: This case highlights the challenges
      that providers may face when dealing with life-threatening bleeding in patients
      receiving dabigatran.

PMID- 22595630
TI  - The utility of wet prep in predicting Neisseria gonorrhoeae and Chlamydia
      trachomatis.
AB  - BACKGROUND: Diagnosing Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG)
      cervical infections can be difficult in the Emergency Department without real
      time testing, as historical and physical elements are known to be unreliable.
      OBJECTIVE: To evaluate the utility of the vaginal wet mount preparation (wet
      prep) in predicting an infection with NG or CT. METHODS: A retrospective chart
      review was performed on 12 months of data from September 2007 to August 2008 on
      patients aged 18 years and above who had a chief complaint requiring a pelvic
      examination and had concurrent testing for NG/CT and a wet prep. Wet preps were
      analyzed and reported as quantity of white cells and clue cells present (none,
      few, moderate, or many) as well as the presence of Trichomonas vaginalis (TV).
      Wet prep results were evaluated to see if there was a correlation with NG/CT.
      RESULTS: There were 2439 patient encounters reviewed. A total of 373/2439 (15.3%)
      patient encounters were positive for NG or CT; 272/2439 (11.2%) were positive for
      TV, whereas 966/2439 (39.6%) had white cells and 995/2439 (40.8%) had clue cells
      on wet prep. Clue cells and TV did not correlate with the presence of NG or CT.
      Only the presence of "moderate" and "many" white cells correlated with NG or CT
      (odds ratio [OR] 1.58, 95% confidence interval [CI] 1.12-2.22 and OR 2.47, 95% CI
      1.86-3.27, respectively). CONCLUSION: In patients who are diagnosed with NG or
      CT, the presence of TV or clue cells on wet prep is an unreliable marker for
      diagnosis. However, having moderate or many white cells present on wet prep does
      increase the probability of concurrent NG or CT infection and may be used in
      cases where the clinical suspicion is equivocal.

PMID- 22595631
TI  - A pilot study examining the viability of a Prehospital Assessment with UltraSound
      for Emergencies (PAUSE) protocol.
AB  - BACKGROUND: Prehospital ultrasound has been shown to aid in the diagnosis of
      multiple conditions that do not generally change prehospital management. On the
      other hand, the diagnoses of cardiac tamponade, tension pneumothorax, or cardiac
      standstill may directly impact patient resuscitation in the field. STUDY
      OBJECTIVE: To determine if prehospital care providers can learn to acquire and
      recognize ultrasound images for several life-threatening conditions using the
      Prehospital Assessment with UltraSound for Emergencies (PAUSE) protocol. METHODS:
      This is a prospective, educational intervention pilot study at an urban fire
      department with integrated emergency medical services (EMS). We enrolled 20
      emergency medical technicians--paramedic with no prior ultrasonography training.
      Subjects underwent a 2-h training session on basic ultrasonography of the lungs
      and heart to evaluate for pneumothorax, pericardial effusion, and cardiac
      activity. Subjects were tested on image interpretation as well as image
      acquisition skills. Two bedside ultrasound-trained emergency physicians scored
      images for adequacy. Image interpretation testing was performed using pre
      obtained ultrasound clips containing normal and abnormal images. RESULTS: All
      subjects appropriately identified the pleural line, and 19 of 20 paramedics
      achieved a Cardiac Ultrasound Structural Assessment Scale score of >=4. For the
      image interpretation phase, the mean PAUSE protocol video test score was 9.1 out
      of a possible 10 (95% confidence interval 8.6-9.6). CONCLUSION: Paramedics were
      able to perform the PAUSE protocol and recognize the presence of pneumothorax,
      pericardial effusion, and cardiac standstill. The PAUSE protocol may potentially
      be useful in rapidly detecting specific life-threatening pathology in the
      prehospital environment, and warrants further study in existing EMS systems.

PMID- 22595632
TI  - Would earlier microbe identification alter antibiotic therapy in bacteremic
      emergency department patients?
AB  - BACKGROUND: Although debate exists about the treatment of sepsis, few disagree
      about the benefits of early, appropriately targeted antibiotic administration.
      STUDY OBJECTIVES: To determine the appropriateness of empiric antimicrobial
      therapy and the extent to which therapy would be altered if the causative
      organism for sepsis was known at the time of administration. METHODS: This was a
      retrospective cohort study, conducted in an academic Emergency Department (ED),
      on consecutive positive blood cultures between November 1, 2008 and February 1,
      2009. Blood cultures and the appropriateness of administered antimicrobial
      therapy were evaluated. Therapy choices were categorized based on whether or not
      a physician, complying with antimicrobial guidelines, would have made changes to
      empiric antibiotic therapy had the causative organism initially been known.
      RESULTS: There were 90 positive blood cultures obtained from 84 patients. Of
      these, 21.1% (n=19) were considered contaminants. The final categorization of
      empiric antibiotics given in the ED for the remaining blood culture results were:
      1) therapy would be changed to narrower-spectrum antibiotics (n=34, 55.7%); 2)
      therapy would be changed because the organism was not covered (n=13, 21.3%); and
      3) therapy would remain the same (n=14, 23.0%). There was 90.2% inter-rater
      agreement for these classifications (p<0.0001), with a kappa of 0.84. Polymerase
      chain reaction analysis had a statistically significant advantage (p<0.0001) over
      Infectious Disease Society of America protocols in facilitating accurate
      antimicrobial therapies. CONCLUSION: This study confirms the need for more rapid
      and accurate laboratory methods for bloodstream pathogen identification.

PMID- 22595633
TI  - Reverse Takotsubo cardiomyopathy in the setting of anaphylaxis treated with high
      dose intravenous epinephrine.
AB  - BACKGROUND: Takotsubo cardiomyopathy is seen, though rarely, in anaphylaxis
      treated with epinephrine. Stress cardiomyopathy is most likely to occur in middle
      aged women. The underlying etiology is believed to be related to catecholamine
      release in periods of intense stress. Catecholamines administered exogenously,
      and those secreted by neuroendocrine tumors (e.g., pheochromocytoma) or during
      anaphylaxis have been reported to cause apical ballooning syndrome, or takotsubo
      syndrome. However, reverse takotsubo stress cardiomyopathy is rarely seen or
      reported in anaphylaxis treated with epinephrine. OBJECTIVES: To report a case
      illustrating that high-dose intravenous epinephrine can trigger stress
      cardiomyopathy, and that the risk is heightened with inappropriate dosing in the
      treatment of anaphylaxis. CASE REPORT: We report a rare case of iatrogenic
      reverse takotsubo syndrome in a young woman who was inappropriately treated with
      high-dose intravenous epinephrine for mild anaphylaxis. CONCLUSION:
      Inappropriately high doses of intravenous epinephrine can trigger stress
      cardiomyopathy. Emergency physicians should be familiar with the diagnosis,
      grading, and appropriate treatments of anaphylaxis to avoid this unnecessary
      complication.

PMID- 22595635
TI  - Mucin 6 and Tn antigen expression in canine mammary tumours: correlation with
      pathological features.
AB  - Overexpression of mucins is known to decrease cell-to-cell adhesion and thus to
      facilitate the invasion of cancer cells through the extracellular matrix. Mucin 6
      (MUC6) is overexpressed and aberrantly O-glycosylated in human breast cancer,
      serving as a carrier for one of the most specific cancer-associated antigens, Tn
      antigen. Despite its relevance in breast cancer, MUC6 expression has not yet been
      characterized in canine mammary tumours (CMTs). The aims of this study were to
      assess the expression of MUC6 and Tn antigen in 55 benign and 77 malignant CMTs
      of different histological types and to investigate possible correlations with
      pathological features. MUC6 and Tn antigen were found to be significantly
      overexpressed in malignant compared with benign CMTs. MUC6 was significantly
      overexpressed in simple and complex carcinomas compared with simple and complex
      adenomas, respectively. When considering only the epithelial population,
      significant MUC6 overexpression was observed in carcinosarcomas when compared
      with benign mixed tumours. In addition, MUC6 was significantly overexpressed in
      simple compared with complex carcinomas. Finally, double-labelling
      immunofluorescence performed on seven malignant CMTs showed MUC6 and Tn co
      expression. Therefore, MUC6 and Tn antigen overexpression is associated with
      malignant phenotypes of CMTs.

PMID- 22595637
TI  - [New ways of consuming alcohol].

PMID- 22595636
TI  - [Nevus flammeus, aberrant mongolian spot and neurological symptoms].

PMID- 22595634
TI  - Disease-associated prion protein in neural and lymphoid tissues of mink (Mustela
      vison) inoculated with transmissible mink encephalopathy.
AB  - Transmissible spongiform encephalopathies (TSEs) are diagnosed by immunodetection
      of disease-associated prion protein (PrP(d)). The distribution of PrP(d) within
      the body varies with the time-course of infection and between species, during
      interspecies transmission, as well as with prion strain. Mink are susceptible to
      a form of TSE known as transmissible mink encephalopathy (TME), presumed to arise
      due to consumption of feed contaminated with a single prion strain of ruminant
      origin. After extended passage of TME isolates in hamsters, two strains emerge,
      HY and DY, each of which is associated with unique structural isoforms of
      PrP(TME) and of which only the HY strain is associated with accumulation of
      PrP(TME) in lymphoid tissues. Information on the structural nature and lymphoid
      accumulation of PrP(TME) in mink is limited. In this study, 13 mink were
      challenged by intracerebral inoculation using late passage TME inoculum, after
      which brain and lymphoid tissues were collected at preclinical and clinical time
      points. The distribution and molecular nature of PrP(TME) was investigated by
      techniques including blotting of paraffin wax-embedded tissue and epitope mapping
      by western blotting. PrP(TME) was detected readily in the brain and
      retropharyngeal lymph node during preclinical infection, with delayed progression
      of accumulation within other lymphoid tissues. For comparison, three mink were
      inoculated by the oral route and examined during clinical disease. Accumulation
      of PrP(TME) in these mink was greater and more widespread, including follicles of
      rectoanal mucosa-associated lymphoid tissue. Western blot analyses revealed that
      PrP(TME) accumulating in the brain of mink is structurally most similar to that
      accumulating in the brain of hamsters infected with the DY strain. Collectively,
      the results of extended passage in mink are consistent with the presence of only
      a single strain of TME, the DY strain, capable of inducing accumulation of
      PrP(TME) in the lymphoid tissues of mink but not in hamsters. Thus, mink are a
      relevant animal model for further study of this unique strain, which ultimately
      may have been introduced through consumption of a TSE of ruminant origin.

PMID- 22595638
TI  - [A child with calcinosis and dermatological signs of connective tissue disease].

PMID- 22595639
TI  - Development of a micro dosing system for fine powder using a vibrating capillary.
      Part 1: the investigation of factors influencing on the dosing performance.
AB  - Precise filling of powder in pharmaceutical development and production is still a
      challenge, especially when handling small quantities of high potency actives. For
      this purpose, a micro dosing system for fine powder using a vibrating capillary
      was developed and investigated. The main objective in this work focused on flow
      rate and its variability in relation to parameters such as capillary diameter,
      frequency, and amplitude. The impact of powder properties such as density,
      particle size, size distribution and shape was also studied with five different
      kinds of lactose powder. It was found that both the frequency and the amplitude
      affect the flow rate and variability but with different impact. The range of flow
      rate can vary from 1mg to 10mg per second and a relative standard deviation of
      better than 3% can be achieved.

PMID- 22595640
TI  - Niosomes and discomes for ocular delivery of naltrexone hydrochloride:
      morphological, rheological, spreading properties and photo-protective effects.
AB  - Naltrexone hydrochloride (NTX) is a promising treatment for corneal disorders
      linked to diabetes mellitus (diabetic keratopathy). However, NTX has a major
      stability problem due to autoxidation, which is likely to hinder its formulation
      as eye drops for treatment of diabetic keratopathy. In this study, in-house
      developed NTX non-ionic surfactant vesicles (niosomes and discomes) were
      evaluated for their spreading, rheological properties and their ability to impede
      the inevitable autoxidation of NTX in aqueous solutions. The measured contact
      angles and spreading coefficients for niosomes reflected significantly (P<0.05)
      better wetting and spreading abilities than the aqueous vehicle. The prepared
      niosomes were significantly more viscous (P<0.05) than the aqueous solution. The
      lipid content, size and composition of niosomes are the main factors affecting
      the viscosity of niosomal dispersions. Exposure of NTX solution to artificial
      daylight illumination (10,000 lux) can produce extensive degradation of NTX due
      to oxidation. The prepared formulations were able to significantly (P<0.05)
      protect the encapsulated NTX from the photo-induced oxidation compared with free
      NTX solutions. The investigated niosomes lend themselves as a potential ocular
      delivery modality for NTX.

PMID- 22595641
TI  - Can magnetic resonance imaging of the hand and wrist differentiate between
      rheumatoid arthritis and psoriatic arthritis in the early stages of the disease?
AB  - OBJECTIVE: To investigate whether rheumatoid arthritis (RA) and psoriatic
      arthritis (PsA) can be differentiated in the early stages of the disease
      (duration of symptoms <=1 year) on the basis of magnetic resonance imaging (MRI)
      features of the hand and wrist. MATERIAL AND METHODS: Twenty early RA and 17
      early PsA patients with symptomatic involvement of the wrist and hand joints and
      inconclusive radiographic studies were examined prospectively with contrast
      enhanced MRI. Images were evaluated in accordance with the Outcome Measures in
      Rheumatology Clinical Trials recommendations. RESULTS: Certain MRI features, such
      as the presence of enthesitis or extensive diaphyseal bone marrow edema, were
      observed exclusively in PsA (P = 0.0001). These distinctive findings were present
      in nearly 71% (12/17) of PsA patients. Diffuse and, in some cases, pronounced
      soft-tissue edema spreading to the subcutis was also seen more frequently in
      patients with PsA (P = 0.002). There were no significant differences in the
      frequency of synovitis, bone erosions, subchondral bone edema, or tenosynovitis
      between the 2 groups. However, in RA extensor tendons were involved more often
      than the flexor tendons, whereas in PsA the opposite was observed (P = 0.014).
      With respect to the discriminatory power of the different MRI findings examined,
      only the presence of enthesitis or diaphyseal bone edema and, to a lesser extent,
      the pattern of hand tendon involvement and the presence of soft-tissue edema
      accurately differentiated PsA from RA (all these features achieved accuracies
      greater than 0.70). CONCLUSIONS: We observed significant differences in the MRI
      findings of the hand and wrist that can help to distinguish between RA and PsA in
      the early stages of disease. This imaging method could help to assist in the
      differential diagnostic process in selected patients in whom diagnosis cannot be
      unequivocally established after conventional clinical, biochemical, and
      radiographic examinations.

PMID- 22595642
TI  - Neuropsychiatric lupus: the prevalence and autoantibody associations depend on
      the definition: results from the 1000 faces of lupus cohort.
AB  - OBJECTIVES: The (ever) prevalence of neuropsychiatric systemic lupus
      erythematosus (NPSLE) can vary widely depending on the definition used. We
      determined the prevalence of NPSLE in 1000 Faces of Lupus, a large multicenter
      Canadian cohort. METHODS: Adults enrolled at 10 sites who satisfied the American
      College of Rheumatology (ACR) classification for systemic lupus erythematosus
      (SLE) were included. NPSLE was defined as (i) NPSLE by ACR classification
      criteria (seizures or psychosis), (ii) ACR, SLEDAI (seizure, psychosis, organic
      brain syndrome, cranial nerve disorder, headache, and cerebrovascular accident
      (CVA)), SLAM (CVA, seizure, cortical dysfunction, and headache), and SLICC
      (cognitive impairment, psychosis, seizures, CVA, cranial or peripheral
      neuropathy, and transverse myelitis) with and (iii) without minor nonspecific
      NPSLE manifestations (including mild depression, mild cognitive impairment, and
      electromyogram-negative neuropathies), and (iv) by ACR and SLEDAI
      neuropsychiatric (NP) indexes alone. Factors associated with NPSLE were explored
      using regression models. RESULTS: Cohort size was 1253, with mean disease 12 +/-
      10 years, mean age 41 +/- 16 years, and 86% female. Subgroup size was dependent
      on the specific definition of NPSLE. Prevalence of NPSLE was 6.4% in group (i), n
      = 1253 (n = 80); 38.6% in group (ii), n = 681(n = 263); 28.7% in group (iii), n =
      586 (n = 168); and 10.2% in group (iv), n = 1125 (n = 115). In univariate
      analysis, Aboriginals had a nearly 2-fold increase in frequency of NPSLE in all
      groups. Education level and income were not associated with NPSLE (P = 0.32 and
      0.03, respectively). As well, number of ACR criteria, SLAM, age at diagnosis,
      disease duration, and gender were not associated with NPSLE. Anti-Ro was
      significantly associated in groups (i) and (iv) and antiphospholipid antibodies
      (aPL) were increased in groups (i), (ii), and (iii); however, this lost
      significance when thromboembolic events were excluded from SLICC, SLEDAI, and
      SLAM indexes. In group (iv), absence of anti-Sm was significant. In multivariate
      analysis, anti-Ro and aPL (i) and anti-Ro+ and lack of anti-Sm (iv) were
      significant. NPSLE was not increased in those with +anti-DNA, La, or
      ribonucleoprotein (RNP), lupus anticoagulant (LAC), or anticardiolipin (aCL)
      antibody. CONCLUSIONS: The prevalence and factors associated with NPSLE varied
      depending on the definition used, was highest in Aboriginals, and may be higher
      if +anti-Ro or aPL are present. SLAM and SLICC include mild subjective disease
      manifestations, which contributed to a 10% higher prevalence of NPSLE compared to
      a more strict definition. NPSLE may be less in this database than other
      publications as its overall prevalence may be decreasing, or because of selection
      bias inherent to those who enter an observational cohort. NPSLE was associated
      with aPL and often anti-Ro and varied by ethnicity.

PMID- 22595644
TI  - Crowding versus molecular seeding: NMR studies of protein aggregation in hen egg
      white.
AB  - In living systems, proteins are surrounded by many other macromolecules of
      different nature, at high total concentrations. In the last few years, there has
      been an increasing effort to study biological macromolecules directly in natural
      crowded environments, such as in intact bacterial cells or by mimicking natural
      crowding by adding proteins, polysaccharides or even synthetic polymers. We have
      recently proposed hen egg white (HEW) as a suitable, natural medium to study
      macromolecules in crowding conditions. Here, we show that HEW can increase
      dramatically the aggregation kinetics of proteins with an in-built tendency to
      associate. By dissecting the mechanism we demonstrate that only part of this
      effect is due to crowding, while another factor playing an important role is the
      interaction with proteins from the milieu. High molecular weight glycoproteins
      present in HEW act as efficient molecular seeds for aggregation. Our results bear
      important consequences for in-cell NMR studies and suggest a role of glycosylated
      proteins in aggregation.

PMID- 22595643
TI  - Risk of significant infection in rheumatoid arthritis patients switching anti
      tumor necrosis factor-alpha drugs.
AB  - OBJECTIVES: To describe rates of first significant infection of rheumatoid
      arthritis patients who switch between anti-tumor necrosis factor (aTNF) drugs.
      METHODS: Subjects with rheumatoid arthritis who received only aTNF drugs were
      observed in an insurance claims database from January 2001 to December 2007.
      Nonswitchers (NS) remained on one aTNF throughout the study period (date of the
      first aTNF claim was the index date); switchers (S) received at least one other
      aTNF (claim date for the 2nd agent was the index date). Significant infections
      included those that required intravenous antibiotics or hospitalization. Two
      attributable risk periods were used: (1) an infection occurring <=90 days
      following a claim for an aTNF (90-day) and (2) an infection occurring after the
      index date (ever-treated). Follow-up was censored at the first occurrence of a
      significant infection event, end of eligibility, or end of study period. Data
      were analyzed using Cox regression. RESULTS: In 13,752 NS and 2293 S patients,
      time-stratified rates declined 2- to 3-fold between the first year versus >=2
      years. Risk of significant infection was not different for either attribution
      model [90-day hazard ratio (HR) = 0.93, 95CI: 0.74 to 1.17, P = 0.55; ever
      treated HR = 0.94, 95CI: 0.78 to 1.15, P = 0.57]. First and second year rates
      were similar. Predictors included age >=50 years; history of significant or
      opportunistic infection, diabetes, respiratory disease; Charlson score >=2; or
      prior hospitalizations. CONCLUSIONS: The risk of a significant infection was not
      different between NS and S patients. Regardless of switching status, the rate of
      infection was greater in the first year. This study was limited by the lack of
      clinical data to determine the reason for switching.

PMID- 22595645
TI  - Patients with unrecognized peripheral arterial disease (PAD) assessed by ankle
      brachial index (ABI) present a defined profile of proinflammatory markers
      compared to healthy subjects.
AB  - BACKGROUND: Many studies have postulated that atherosclerosis should be
      considered as an inflammatory disease. In addition, some studies have focused on
      the relationship between inflammation and peripheral arterial disease (PAD).
      OBJECTIVE: Define the plasma levels of soluble markers, including the
      proinflammatory cytokine interleukin-6 (IL-6), the anti-inflammatory cytokine
      transforming growth factor-beta1 (TGF-beta1), the endothelial-specific adhesion
      factor (E-selectin) and two proteinases involved in extracellular matrix
      degradation (matrix metalloproteinases-2 and -9, MMP-2, and MMP-9) in previously
      unrecognized patients with peripheral artery disease (PAD) and non-PAD controls.
      RESULTS: Significantly higher levels of IL-6, E-selectin and MMP-2/MMP-9 and
      significantly reduced levels of TGF-beta1 were found in PAD patients (ankle
      brachial index, ABI?0.9) compared to non-PAD control subjects (1.4>ABI>0.9).
      CONCLUSION: The results demonstrated the subjects with unrecognized PAD (ABI?0.9)
      show a characteristic phlogistic pattern differently from healthy subjects and it
      strongly supports the pivotal role played by inflammatory and immunological
      mechanisms in the initiation and progression of the atherosclerotic process in
      peripheral arteries. These biomarkers could be helpful to screen the
      susceptibility for the diseases in peripheral arteries.

PMID- 22595646
TI  - IL10, IL11, IL18 are differently expressed in CD14+ TAMs and play different role
      in regulating the invasion of gastric cancer cells under hypoxia.
AB  - BACKGROUND: Recent evidence shows that chronic inflammation mediated by tumor
      associated macrophage (TAM) play an important role in malignant tumor formation
      and progression. Interleukins expressed in TAMs regulate this progress. Hypoxia
      is a salient feature of solid tumors and has a profound influence on the biology
      of TAMs However, the role of interleukins in the gastric cancer progression under
      hypoxia is not clear. METHODS: Realtime RT-PCR was used to quantitatively
      investigate the IL10, IL11 and IL18 expression in CD14(-) normal macrophages and
      CD14(+) TAMs co-cultured with four gastric cancer cell lines including non
      metastatic cell line AGS and metastatic cell lines HGC-27, Hs-746T and NCI-N87
      under normal or hypoxic conditions. In addition, the correlation between IL10,
      IL11, IL18 expression in TAMs under hypoxia and mobility of gastric cancer cells
      were analyzed. RESULTS: Under normal conditions, the IL10 and IL18 expressions
      were significantly higher in CD14(+) TAMs co-cultured with non-metastatic cell
      line than with metastatic cell lines. IL11 expression was significantly higher in
      CD14(+) TAMs co-cultured with distant metastasis cell lines. Hypoxia induced
      IL10, IL11 and IL18 expression up regulated significantly in TAMs co-cultured
      with AGS, Hs-746T and NCI-N87 cell line. There was a significant negative
      correlation between IL11 expression in CD14(+) TAMs and gastric cancer cell
      invasion speed under hypoxic conditions (r=0.861, P<0.001). CONCLUSION: The up
      regulation of IL10, IL11 and IL18 expression in TAMs by hypoxia differed in
      gastric cancer cell lines. IL11 expression in TAMs might play more important role
      than IL10 and IL18 expression in regulating the invasion of gastric cancer cells
      under hypoxia.

PMID- 22595647
TI  - Genetic susceptibility to chronic Chagas disease: an overview of single
      nucleotide polymorphisms of cytokine genes.
AB  - Chagas disease is a parasitic infection that is a significant public health
      problem in Latin America. The mechanisms responsible for susceptibility to the
      infection and the mechanisms involved in the development of cardiac and digestive
      forms of chronic Chagas disease remain poorly understood. However, there is
      growing evidence that differences in susceptibility in endemic areas may be
      attributable to host genetic factors. The aim of this overview was to analyze the
      genetic susceptibility to human Chagas disease, particularly that of single
      nucleotide polymorphisms of cytokine genes. A review of the literature was
      conducted on the following databases: PubMed/MEDLINE and Scopus. The search
      strategy included using the following terms: "Cytokines", "Single Nucleotide
      Polymorphisms" and "Chagas Disease". After screening 25 citations from the
      databases, 19 studies were selected for the overview. A critical analysis of the
      data presented in the articles suggests that genetic susceptibility to Chagas
      disease and chronic Chagas cardiomyopathy is highly influenced by the complexity
      of the immune response of the host. Follow-up studies based on other populations
      where Chagas disease is endemic (with distinct ethnic and genetic backgrounds)
      need to be conducted. These should use a large sample population so as to
      establish what cytokine genes are involved in susceptibility to and/or
      progression of the disease.

PMID- 22595648
TI  - 21 Days head-down bed rest induces weakening of cell-mediated immunity - Some
      spaceflight findings confirmed in a ground-based analog.
AB  - Several studies indicate a weakening of cell-mediated immunity (CMI) and
      reactivation of latent herpes viruses during spaceflight. We tested the
      hypothesis that head-down bed rest (HDBR), a ground-based analog of spaceflight,
      mimics the impact of microgravity on human immunity. Seven healthy young males
      underwent two periods of 3 weeks HDBR in the test facility of the German
      Aerospace Center. As a nutritional countermeasure aimed against bone
      demineralisation, 90 mmol potassium bicarbonate (KHCO(3)) was administered daily
      in a crossover design. Blood samples were drawn on five occasions. Whole blood
      was stimulated with antigen i.e. Candida albicans, purified protein derivative
      (PPD) tuberculin, tetanus toxoid and Cytomegalovirus (CMV) (CMV-QuantiFERON).
      Flow cytometric analysis included CD4(+)CD25(+)CD127(-)FOXP3(+) regulatory T
      cells (Tregs), gammadelta T cells, B cells, NK cells and dendritic cells. In one
      of the two bed rest periods, we observed a significant decrease in production of
      interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and tumor necrosis factor
      alpha (TNF-alpha) following phytohemagglutinin (PHA) stimulation, with a rapid
      normalization being observed after HDBR. The cytokine levels showed a V-shaped
      pattern that led to a relativeTh2-shift in cytokine balance. Only three
      individuals responded to the specific T cell antigens without showing signs of an
      altered response during HDBR, nor did we observe reactivation of CMV or Epstein
      Barr virus (EBV). Of unknown significance, dietary supplementation with KHCO(3)
      counteracted the decrease in IL-2 levels during HDBR, while there was no impact
      on other immunological parameters. We conclude that discrete alterations in CMI
      may be induced by HDBR in selected individuals.

PMID- 22595650
TI  - Disaster metrics: a proposed quantitative model for benchmarking prehospital
      medical response in trauma-related multiple casualty events.
AB  - INTRODUCTION: Quantitative benchmarking of trauma-related prehospital response
      for Multiple Casualty Events (MCE) is complicated by major difficulties due to
      the simultaneous occurrences of multiple prehospital activities.
      HYPOTHESIS/PROBLEM: Attempts to quantify the various components of prehospital
      medical response in MCE have fallen short of a comprehensive model. The objective
      of this study was to model the principal parameters necessary to quantitatively
      benchmark the prehospital medical response in trauma-related MCE. METHODS: A two
      step approach was adopted for the methodology of this study: an extensive
      literature search was performed, followed by prehospital system quantitative
      modeling. Studies on prehospital medical response to trauma injuries were used as
      the framework for the proposed model. The North Atlantic Treaty Organization
      (NATO) triage categories (T1-T4) were used for the study. RESULTS: Two
      parameters, the Injury to Patient Contact Interval (IPCI) and Injury to Hospital
      Interval (IHI), were identified and proposed as the principal determinants of the
      medical prehospital response in trauma-related MCE. IHI is the time interval from
      the occurrence of injury to the completion of transfer of care of critical (T1)
      and moderate (T2) patients. The IHI for each casualty is compared to the Maximum
      Time Allowed described in the literature (golden hour for T1 and Friedrich's time
      for T2). In addition, the medical rescue factor (R) was identified as the overall
      indicator for the prehospital medical performance for T1 and T2, and a numerical
      value of one (R = 1) was proposed to be the quantitative benchmark. CONCLUSION: A
      new quantitative model for benchmarking prehospital response to MCE in trauma
      related MCE is proposed. Prospective studies of this model are needed to validate
      its applicability.

PMID- 22595649
TI  - Interleukin-6 signaling regulates anchorage-independent growth, proliferation,
      adhesion and invasion in human ovarian cancer cells.
AB  - It has been widely reported that Interleukin-6 (IL-6) is overexpressed in the
      serum and ascites of ovarian cancer (OVCA) patients, and elevated IL-6 level
      correlates with poor prognosis and survival. However, the exact role that IL-6
      plays in this malignancy or whether IL-6 can regulate tumorigenic properties has
      not been established. Here we demonstrate that overexpression of IL-6 in non-IL-6
      expressing A2780 cells (by transfecting with plasmid encoding for sense IL-6)
      increases anchorage-independent growth, proliferation, adhesion and invasion,
      while depletion of endogenous IL-6 expression in IL-6-overexpressing SKOV-3 cells
      (by transfecting with plasmid encoding for antisense IL-6) decreases. Further
      investigation indicates that IL-6 promotes OVCA cell proliferation by altering
      cell cycle distribution rather than inhibiting apoptosis and that IL-6-enhanced
      OVCA cell invasive may be associated with increased matrix metalloproteinase
      (MMP)-9 but not MMP-2 proteolytic activity. In addition, overexpressing or
      deleting of IL-6 in OVCA cells enhances or reduces its receptor (IL-6Ralpha and
      gp130) expression and basal phosphorylation levels of both ERK and Akt, and
      additional treatment with specific inhibitor of the ERK or Akt signaling pathway
      significantly inhibits the proliferation of IL-6-overexpressing A2780 cells. Our
      data suggest that the autocrine production of IL-6 by OVCA cells regulates
      tumorigenic properties of these cells by inducing IL-6 signaling pathways. Thus,
      regulation of IL-6 expression or its related signaling pathway may be a promising
      strategy for controlling the progression of OVCA.

PMID- 22595651
TI  - Intestinal ciliate composition found in the feces of racing horses from Izmir,
      Turkey.
AB  - Species composition and distribution of intestinal ciliates were investigated in
      the feces from 15 racing horses living near Izmir, Turkey. Thirty-seven species
      belonging to 21 genera were identified. Although no new species were observed,
      this is the first report on intestinal ciliates in racing horses living in
      Turkey. The mean number of ciliates was 26.4 +/- 13.9 * 10(4) cells ml(-1) of
      feces and the mean number of ciliate species per host was 18.8 +/- 7.1. No
      ciliates were observed in one horse. Bundleia and Polymorphella were found to be
      the two dominant genera, occurring in high proportions. In contrast, Didesmis and
      Prorodonopsis were only observed at a low frequency. Bundleia nana, Blepharoconus
      hemiciliatus, Paraisotrichopsis composita, Prorodonopsis coli and Spirodinium
      equi were newly recorded from Turkey.

PMID- 22595652
TI  - Establishment of a new hypotrichous genus, Heterotachysoma n. gen. and notes on
      the morphogenesis of Hemigastrostyla enigmatica (Ciliophora, Hypotrichia).
AB  - A marine hypotrich ciliate, Heterotachysoma multinucleatum (Gong and Choi, 2007)
      n. comb., found in coastal waters near Qingdao, China, was investigated.
      Heterotachysoma multinucleatum is characterized by its dorsal ciliature arranged
      in Gonostomum-pattern. Additionally, a new genus, Heterotachysoma n. gen., is
      established which is mainly characterized by: 18-cirri pattern; flexible body;
      three dorsal kineties with no dorsomarginal kineties nor kinety fragmentation;
      one right and one left row of marginal cirri; caudal cirri absent. The genus
      Tachysoma is redefined, and three new combinations, T. multinucleatum, T. ovatum
      and T. dragescoi, are proposed. The morphogenesis of Hemigastrostyla enigmatica
      (Dragesco and Dragesco-Kerneis, 1986) Song and Wilbert, 1997, is also described.
      Compared with that of its congeners, the differences are mainly in the dorsal
      ciliature: (1) the dorsal kinety anlagen are formed de novo in H. enigmatica (vs.
      intrakinetally in H. paraenigmatica and H. elongata); (2) the dorsal kineties
      anlagen develop in secondary mode in H. enigmatica (vs. primary mode in H.
      paraenigmatica); (3) the kinetal fragment anterior to the right marginal row in
      both filial product is absent in both H. enigmatica and H. elongata (vs. present
      in H. paraenigmatica). These findings suggest that morphogenesis is not uniform
      among members of the genus Hemigastrostyla.

PMID- 22595653
TI  - Spatial genetic variation, phylogeography and barcoding of the peritrichous
      ciliate Carchesium polypinum.
AB  - Most recent studies of geographic distribution of microbial eukaryotes have
      focused on marine rather than freshwater protists. Here, we used the freshwater
      peritrich ciliate Carchesium polypinum to quantify the degree of genetic
      diversity of four closely related and previously described lineages and to
      determine whether patterns of genetic differentiation showed geographic
      partitioning. Using an expanded dataset of 100 isolates and employing the
      mitochondrial marker cytochrome oxidase c subunit I (cox-1), we enriched the 6
      previously identified clades of Carchesium polypinum. We found a large degree of
      geographic overlap among the different clades (e.g. to the level of range of
      sampling), but also a spatially restricted clade (e.g. to the level of one river
      basin). Furthermore, we present evidence of a clear geographic separation in one
      of the lineages with Canadian and North Carolinian isolates grouping in two
      distinct clusters.

PMID- 22595654
TI  - Patterns of physical activity and sedentary behavior in normal-weight, overweight
      and obese adults, as measured with a portable armband device and an electronic
      diary.
AB  - BACKGROUND & AIMS: Accurate data on domain-specific physical activity and
      sedentary behavior among normal-weight, overweight and obese adults are scarce.
      This study described a comprehensive physical (in)activity profile and examined
      variations in activity across the week. METHODS: Physical activity was measured
      in 442 Flemish adults (41.4 +/- 9.8 years) for 7 days using the SenseWear Armband
      and an electronic diary. Differences in (in)activity between BMI subgroups were
      examined using one-way analyses of variance. RESULTS: Physical activity level
      decreased with increasing BMI in men (1.77-1.46 MET) and women (1.67-1.31 MET).
      Sedentary time was higher in obese than normal-weight men (+1.09 h/day) and
      overweight and obese than normal-weight women (+1.04 and +1.88 h/day). Total
      hours of moderate-to-vigorous activity and bouts of moderate-to-vigorous activity
      were lower in overweight and obese than normal-weight subjects. The average
      duration of a sedentary bout and the number of breaks in sedentary time were only
      different between female BMI groups. The intensity of domain-specific activities
      decreased with increasing BMI. Activity patterns across the week differed between
      subgroups, with the difference most pronounced on Saturday for the male BMI
      groups. CONCLUSIONS: This study described activity patterns among normal-weight,
      overweight and obese adults. The results should be used to design obesity
      prevention strategies.

PMID- 22595656
TI  - Evaluation of the Dutch AIDS STI information helpline: differential outcomes of
      telephone versus online counseling.
AB  - OBJECTIVE: Health information helplines have an important function in health
      education, prevention and counseling. Information and help services are
      increasingly provided online. This study focuses on the differences and
      similarities between online help services and telephone services. METHODS: The
      telephone service of the Dutch AIDS STI helpline was compared to its e-mail
      equivalent. After consulting the helpline service, both callers and e-mailers
      (N(tot) = 455) were asked to participate in a survey that evaluated their
      background characteristics, contacting reasons, and satisfaction with the
      specific service and information received. The survey also included questions
      regarding the advice received from the helpline. A follow-up measure 4 weeks
      after the baseline survey evaluated to what extent clients acted upon the advice.
      RESULTS: The study shows that both services are positively evaluated and are
      equally persuasive in their counseling. Differences between callers and e-mailers
      were found regarding background characteristics, content of the consultation,
      satisfaction, and the advice received. CONCLUSION: It can be concluded that
      online health information services are an important addition to, but not a
      replacement for, the traditional telephone helplines. PRACTICE IMPLICATIONS: In
      order to provide an optimal health service to a wide public, both online and
      telephone counseling should be offered.

PMID- 22595655
TI  - Talking about smoking in primary care medical practice--results of experimental
      studies from the US, UK and Germany.
AB  - OBJECTIVE: To analyse effects of patient and physician characteristics on
      questions and advice about smoking in primary care practice and to examine
      country differences. METHODS: We conducted a factorial experiment, employing
      filmed scenarios in which actors played the role of patients with symptoms of
      coronary heart disease (CHD) or type 2 diabetes. Versions were filmed with
      patient-actors of different gender, age, race, and socioeconomic status. The
      videotapes were presented to primary care physicians in the US, UK and Germany.
      Physicians were asked whether they would ask questions about smoking or give
      cessation advice. RESULTS: Female and older CHD patients are less likely to be
      asked or get advice about smoking in all three countries. Effects of physician
      attributes are weak and inconsistent. Compared to physicians in the US and the
      UK, German doctors are least likely to ask questions or give advice. CONCLUSIONS:
      Although all physicians viewed the same cases their questioning and advice giving
      differed according to patient attributes and country. Due to the experimental
      design external validity of the study may be limited. PRACTICE IMPLICATIONS:
      Findings have implications for medical education and professional training of
      physicians as well as for the organization and financing of health care.

PMID- 22595657
TI  - Comparison of changes in the contraction of the lateral abdominal muscles between
      the abdominal drawing-in maneuver and breathe held at the maximum expiratory
      level.
AB  - The abdominal drawing-in maneuver (ADIM) is commonly used as a fundamental
      component of lumbar stabilization training programs. One potential limitation of
      lumbar stabilization programs is that it can be difficult and time consuming to
      train people to perform the ADIM. The transverse abdominis (TrA), internal
      oblique (IO), and external oblique (EO) muscles are the most powerful muscles
      involved in expiration. However, little is known about the differences in the
      recruitment of the abdominal muscles between the ADIM and breathe held at maximum
      expiratory level (maximum expiration). The thickness of the TrA and IO muscles
      was measured by ultrasound imaging, and the activity of the EO muscle was
      measured by electromyography (EMG) in 33 healthy male performing the ADIM and
      maximum expiration. Maximum expiration produced a significant increase in the
      thickness of the TrA and IO muscles compared to the ADIM (p < 0.001). The EMG
      activity of the EO muscle was significantly higher during maximum expiration than
      during the ADIM (p < 0.001). The intensity of the EMG activity of the EO muscle
      was approximately 30% of the maximal voluntary contraction during maximum
      expiration. Thus, maximum expiration may be an effective method for training of
      co-activation of the lateral abdominal muscles.

PMID- 22595658
TI  - Deficit in the preattentive processing of syllabic duration and VOT in children
      with dyslexia.
AB  - The aim of this experiment was to examine the preattentive processing of
      syllables in 9-11-year-old children with dyslexia and matched controls using the
      Mismatch Negativity (MMN), an auditory Event-Related brain potential (ERP)
      related to preattentive discrimination. Children were presented with a sequence
      of syllables that included standards (the syllable "Ba") and deviants in vowel
      frequency, vowel duration and Voice Onset Time (VOT) that were either close to or
      far from the standard (Small and Large deviants). No between-group differences
      were found for frequency deviants. However, whilst normal-reading children showed
      larger MMNs to Large than to Small deviants in vowel duration and VOT, no such
      deviance size effect was found in children with dyslexia. These results are taken
      to indicate that the preattentive processing of vowel duration and VOT is
      impaired in children with dyslexia, with no impairment in the processing of vowel
      frequency deviants. By revealing processing deficits of both duration and VOT
      deviants, these results suggest a strong link between acoustical and phonological
      processing.

PMID- 22595659
TI  - Setting the tone: an ERP investigation of the influences of phonological
      similarity on spoken word recognition in Mandarin Chinese.
AB  - We investigated the influences of phonological similarity on the time course of
      spoken word processing in Mandarin Chinese. Event related potentials were
      recorded while adult native speakers of Mandarin (N=19) judged whether auditory
      words matched or mismatched visually presented pictures. Mismatching words were
      of the following nature: segmental (e.g., picture: hua1 'flower'; sound: hua4
      'painting'); cohort (e.g., picture: hua1 'flower'; sound: hui1 'gray'); rhyme
      (e.g., picture: hua1 'flower'; sound: gua1 'melon'); tonal (e.g., picture: hua1
      'flower'; sound: jing1 'whale'); unrelated (e.g., picture: hua1 'flower'; sound:
      lang2 'wolf'). Expectancy violations in the segmental condition showed an early
      going modulation of components (starting at 250 ms post-stimulus onset),
      suggesting that listeners used tonal information to constrain word recognition as
      soon as it became available, just like they did with phonemic information in the
      cohort condition. However, effects were less persistent and more left-lateralized
      in the segmental than cohort condition, suggesting dissociable cognitive
      processes underlie access to tonal versus phonemic information. Cohort versus
      rhyme mismatches showed distinct patterns of modulation which were very similar
      to what has been observed in English, suggesting onsets and rimes are weighted
      similarly across the two languages. Last, we did not observe effects for whole
      syllable mismatches above and beyond those for mismatches in individual
      components, suggesting the syllable does not merit a special status in Mandarin
      spoken word recognition. These results are discussed with respect to
      modifications needed for existing models to accommodate the tonal languages
      spoken by a large proportion of the world's speakers.

PMID- 22595660
TI  - Using social media to promote international student partnerships.
AB  - This paper describes a project to establish and evaluate online study
      partnerships, using social networking applications, between final year Canadian
      nursing students at the University of British Columbia (UBC) and second year
      undergraduate science education students at the University of Plymouth (UoP) in
      the UK. The project took place between 2009 and 2010 and evaluated the use of
      social networking applications with international interdisciplinary partnerships
      between Canadian and UK students. A multi-method evaluation strategy
      incorporating questionnaires, online focus groups and web analytics was used to
      explore the value of social media to promote the exchange of ideas and discussion
      of scientific philosophy in different contexts, between students working in
      disciplines with differing philosophical perspectives principally modern/post
      modern, quantitative/qualitative, empirical/theoretical. This project resulted in
      a very successful collaborative partnership between UK and Canadian students.

PMID- 22595661
TI  - Antibacterial activity of selected Cameroonian dietary spices ethno-medically
      used against strains of Mycobacterium tuberculosis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Tuberculosis (TB) is considered as a re-emerging
      disease and one of the most important public health problems worldwide. The use
      or (in most cases) misuse of existint anti-tuberculosis drugs over the years has
      led to an increasing prevalence of resistant strains, establishing an urgent need
      to search for new effective agents. Spices are largely used ethno-medically
      across Africa. AIM OF THE STUDY: The present study aimed to evaluate the in vitro
      antimycobacterial activities of a total of 20 methanol crude extracts prepared
      from 20 Cameroonian dietary spices for their ability to inhibit the growth of or
      kill Mycobacterium tuberculosis strains H(37)Rv (ATCC 27294) and H(37)Ra (ATCC
      25177). MATERIALS AND METHODS: The antituberculosis screening was performed using
      the Microplate Alamar Blue Assay (MABA) method to determine the minimum
      inhibitory concentration (MIC) and the minimum mycobactericidal concentration
      (MBC). RESULTS: Fifteen (15) plant extracts out of 20 showed varied levels of
      antimycobacterial activity against the strains M. tuberculosis H(37)Rv and
      H(37)Ra, with MICs in the range of 2.048-0.016 mg/ml. The extract of Echinops
      giganteus exhibited the most significant activity with a MIC value of 32 MUg/ml
      and 16 MUg/ml, respectively against H(37)Ra and H(37)Rv. To the best of our
      knowledge, the antimycobacterial activity of the tested spices has not been
      reported before and therefore our results can be evaluated as the first report
      about the antimycobacterial properties. CONCLUSIONS: The results of this study
      suggest that Echinops giganteus and Piper guineense could be important sources of
      bactericidal compounds against M. tuberculosis and could probably be promising
      candidates that can be further investigated.

PMID- 22595662
TI  - Transverse myelitis and bilateral optic neuritis in a patient with systemic lupus
      erythematosus.

PMID- 22595663
TI  - A phylotypic stage for all animals?
AB  - A new study in this issue of Developmental Cell (Levin et al., 2012) uses
      comparative transcriptomics and reveals a stage in nematode development that is
      enriched for developmental patterning genes. The molecular profile of this
      phylotypic stage shows similarities with those of vertebrates and flies. The
      findings have important evolutionary implications.

PMID- 22595664
TI  - Pausing on the path to robustness.
AB  - Heat-shock proteins (Hsps) maintain homeostasis by assisting protein folding, and
      the transcriptional regulation of Hsp-coding genes has long been under study.
      Sawarkar et al. (2012) now report in Cell that Hsp90 is itself a transcriptional
      regulator required for RNA polymerase pausing, contributing to rapid, robust
      induction of many genes.

PMID- 22595665
TI  - Cell shape by coercion: Par1 and aPKC put the squeeze on junctions.
AB  - Epithelial sheets form the basic architectural unit of most tissues and organs.
      To form complex organs, these sheets are folded and reshaped by cell-shape
      changes. Reporting recently in Nature, Wang et al. (2012) describe a myosin
      independent mechanism that links the regulation of apical-basal polarity to
      tissue morphogenesis.

PMID- 22595666
TI  - The art of "cut and run": the role of Rab14 GTPase in regulating N-cadherin
      shedding and cell motility.
AB  - Linford et al. define a Rab14-mediated endocytic recycling pathway that controls
      proteolytic N-cadherin cleavage by transporting ADAM10 protease to the plasma
      membrane. When this pathway is disrupted, diminished ADAM10-dependent N-cadherin
      shedding leads to increased cell-cell adhesion and inhibition of cell motility.

PMID- 22595667
TI  - In search of Turing in vivo: understanding Nodal and Lefty behavior.
AB  - The Turing reaction-diffusion model proposes that short-range activators and long
      range inhibitors can generate complex patterns. In a Science study, Muller et al.
      (2012) assess behavioral determinants of Nodal and Lefty, TGFbeta-related
      molecules that constitute an activator/inhibitor system, and provide evidence
      that the factors indeed form a reaction-diffusion system.

PMID- 22595668
TI  - FoxA family members are crucial regulators of the hypertrophic chondrocyte
      differentiation program.
AB  - During endochondral ossification, small, immature chondrocytes enlarge to form
      hypertrophic chondrocytes, which express collagen X. In this work, we demonstrate
      that FoxA factors are induced during chondrogenesis, bind to conserved binding
      sites in the collagen X enhancer, and can promote the expression of a collagen X
      luciferase reporter in both chondrocytes and fibroblasts. In addition, we
      demonstrate by both gain- and loss-of-function analyses that FoxA factors play a
      crucial role in driving the expression of both endogenous collagen X and other
      hypertrophic chondrocyte-specific genes. Mice engineered to lack expression of
      both FoxA2 and FoxA3 in their chondrocytes display defects in chondrocyte
      hypertrophy, alkaline phosphatase expression, and mineralization in their
      sternebrae and, in addition, exhibit postnatal dwarfism that is coupled to
      significantly decreased expression of both collagen X and MMP13 in their growth
      plates. Our findings indicate that FoxA family members are crucial regulators of
      the hypertrophic chondrocyte differentiation program.

PMID- 22595669
TI  - IFT25 links the signal-dependent movement of Hedgehog components to
      intraflagellar transport.
AB  - The intraflagellar transport (IFT) system is required for building primary cilia,
      sensory organelles that cells use to respond to their environment. IFT particles
      are composed of about 20 proteins, and these proteins are highly conserved across
      ciliated species. IFT25, however, is absent from some ciliated organisms,
      suggesting that it may have a unique role distinct from ciliogenesis. Here, we
      generate an Ift25 null mouse and show that IFT25 is not required for ciliary
      assembly but is required for proper Hedgehog signaling, which in mammals occurs
      within cilia. Mutant mice die at birth with multiple phenotypes, indicative of
      Hedgehog signaling dysfunction. Cilia lacking IFT25 have defects in the signal
      dependent transport of multiple Hedgehog components including Patched-1,
      Smoothened, and Gli2, and fail to activate the pathway upon stimulation. Thus,
      IFT function is not restricted to building cilia where signaling occurs, but also
      plays a separable role in signal transduction events.

PMID- 22595670
TI  - Rab14 and its exchange factor FAM116 link endocytic recycling and adherens
      junction stability in migrating cells.
AB  - Rab GTPases define the vesicle trafficking pathways underpinning cell
      polarization and migration. Here, we find that Rab4, Rab11, and Rab14 and the
      candidate Rab GDP-GTP exchange factors (GEFs) FAM116A and AVL9 are required for
      cell migration. Rab14 and its GEF FAM116A localize to and act on an intermediate
      compartment of the transferrin-recycling pathway prior to Rab11 and after Rab5
      and Rab4. This Rab14 intermediate recycling compartment has specific functions in
      migrating cells discrete from early and recycling endosomes. Rab14-depleted cells
      show increased N-cadherin levels at junctional complexes and cannot resolve cell
      cell junctions. This is due to decreased shedding of cell-surface N-cadherin by
      the ADAM family protease ADAM10/Kuzbanian. In FAM116A- and Rab14-depleted cells,
      ADAM10 accumulates in a transferrin-positive endocytic compartment, and the cell
      surface level of ADAM10 is correspondingly reduced. FAM116 and Rab14 therefore
      define an endocytic recycling pathway needed for ADAM protease trafficking and
      regulation of cell-cell junctions.

PMID- 22595671
TI  - ERK1/2 regulate exocytosis through direct phosphorylation of the exocyst
      component Exo70.
AB  - The exocyst is a multiprotein complex essential for exocytosis and plasma
      membrane remodeling. The assembly of the exocyst complex mediates the tethering
      of post-Golgi secretory vesicles to the plasma membrane prior to fusion.
      Elucidating the mechanisms regulating exocyst assembly is important for the
      understanding of exocytosis. Here we show that the exocyst component Exo70 is a
      direct substrate of the extracellular signal-regulated kinases 1/2 (ERK1/2).
      ERK1/2 phosphorylation enhances the binding of Exo70 to other exocyst components
      and promotes the assembly of the exocyst complex in response to epidermal growth
      factor (EGF) signaling. We further demonstrate that ERK1/2 regulates exocytosis,
      because blocking ERK1/2 signaling by a chemical inhibitor or the expression of an
      Exo70 mutant defective in ERK1/2 phosphorylation inhibited exocytosis. In tumor
      cells, blocking Exo70 phosphorylation inhibits matrix metalloproteinase secretion
      and invadopodia formation. ERK1/2 phosphorylation of Exo70 may thus coordinate
      exocytosis with other cellular events in response to growth factor signaling.

PMID- 22595672
TI  - Sec1/Munc18 protein stabilizes fusion-competent syntaxin for membrane fusion in
      Arabidopsis cytokinesis.
AB  - Intracellular membrane fusion requires complexes of syntaxins with other SNARE
      proteins and regulatory Sec1/Munc18 (SM) proteins. In membrane fusion mediating,
      e.g., neurotransmitter release or glucose-stimulated insulin secretion in
      mammals, SM proteins preferentially interact with the inactive closed, rather
      than the active open, conformation of syntaxin or with the assembled SNARE
      complex. Other membrane fusion processes such as vacuolar fusion in yeast involve
      like membranes carrying cis-SNARE complexes, and the role of SM protein is
      unknown. We investigated syntaxin-SM protein interaction in membrane fusion of
      Arabidopsis cytokinesis, which involves cytokinesis-specific syntaxin KNOLLE and
      SM protein KEULE. KEULE interacted with an open conformation of KNOLLE that
      complemented both knolle and keule mutants. This interaction occurred at the cell
      division plane and required the KNOLLE linker sequence between helix Hc and SNARE
      domain. Our results suggest that in cytokinesis, SM protein stabilizes the fusion
      competent open form of syntaxin, thereby promoting trans-SNARE complex formation.

PMID- 22595673
TI  - Kif18A and chromokinesins confine centromere movements via microtubule growth
      suppression and spatial control of kinetochore tension.
AB  - Alignment of chromosomes at the metaphase plate is a signature of cell division
      in metazoan cells, yet the mechanisms controlling this process remain ambiguous.
      Here we use a combination of quantitative live-cell imaging and reconstituted
      dynamic microtubule assays to investigate the molecular control of mitotic
      centromere movements. We establish that Kif18A (kinesin-8) attenuates centromere
      movement by directly promoting microtubule pausing in a concentration-dependent
      manner. This activity provides the dominant mechanism for restricting centromere
      movement to the spindle midzone. Furthermore, polar ejection forces spatially
      confine chromosomes via position-dependent regulation of kinetochore tension and
      centromere switch rates. We demonstrate that polar ejection forces are
      antagonistically modulated by chromokinesins. These pushing forces depend on Kid
      (kinesin-10) activity and are antagonized by Kif4A (kinesin-4), which functions
      to directly suppress microtubule growth. These data support a model in which
      Kif18A and polar ejection forces synergistically promote centromere alignment via
      spatial control of kinetochore-microtubule dynamics.

PMID- 22595674
TI  - Genetic framework of cyclin-dependent kinase function in Arabidopsis.
AB  - Cyclin-dependent kinases (CDKs) are at the heart of eukaryotic cell-cycle
      control. The yeast Cdc2/CDC28 PSTAIRE kinase and its orthologs such as the
      mammalian Cdk1 have been found to be indispensable for cell-cycle progression in
      all eukaryotes investigated so far. CDKA;1 is the only PSTAIRE kinase in the
      flowering plant Arabidopsis and can rescue Cdc2/CDC28 mutants. Here, we show that
      cdka;1 null mutants are viable but display specific cell-cycle and developmental
      defects, e.g., in S phase entry and stem cell maintenance. We unravel that the
      crucial function of CDKA;1 is the control of the plant Retinoblastoma homolog
      RBR1 and that codepletion of RBR1 and CDKA;1 rescued most defects of cdka;1
      mutants. Our work further revealed a basic cell-cycle control system relying on
      two plant-specific B1-type CDKs, and the triple cdk mutants displayed an early
      germline arrest. Taken together, our data indicate divergent functional
      differentiation of Cdc2-type kinases during eukaryote evolution.

PMID- 22595675
TI  - Phf7 controls male sex determination in the Drosophila germline.
AB  - Establishment of germline sexual identity is critical for production of male and
      female germline stem cells, as well as sperm versus eggs. Here we identify PHD
      Finger Protein 7 (PHF7) as an important factor for male germline sexual identity
      in Drosophila. PHF7 exhibits male-specific expression in early germ cells,
      germline stem cells, and spermatogonia. It is important for germline stem cell
      maintenance and gametogenesis in males, whereas ectopic expression in female germ
      cells ablates the germline. Strikingly, expression of PHF7 promotes
      spermatogenesis in XX germ cells when they are present in a male soma. PHF7
      homologs are also specifically expressed in the mammalian testis, and human PHF7
      rescues Drosophila Phf7 mutants. PHF7 associates with chromatin, and both the
      human and fly proteins bind histone H3 N-terminal tails with a preference for
      dimethyl lysine 4 (H3K4me2). We propose that PHF7 acts as a conserved epigenetic
      "reader" that activates the male germline sexual program.

PMID- 22595677
TI  - Protein phosphatase 4 cooperates with Smads to promote BMP signaling in
      dorsoventral patterning of zebrafish embryos.
AB  - BMP signals play pivotal roles in dorsoventral patterning of vertebrate embryos.
      The role of Ppp4c, the catalytic subunit of ubiquitous protein phosphatase 4, in
      vertebrate embryonic development and underlying mechanisms is poorly understood.
      Here, we demonstrate that knockdown of zebrafish ppp4cb and/or ppp4ca inhibits
      ventral development in embryos and also blocks ventralizing activity of ectopic
      Smad5. Biochemical analyses reveal that Ppp4c is a direct binding partner and
      transcriptional coactivator of Smad1/Smad5. In response to BMP, Ppp4c is
      recruited to the Smad1-occupied promoter, and its phosphatase activity is
      essential in inhibiting HDAC3 activity and, consequently, potentiating
      transcriptional activation. Consistently, genetic or chemical interference of
      Hdac3 expression or activity compromises the dorsalizing phenotype induced by
      ppp4cb knockdown. We conclude that Ppp4c is a critical positive regulator of
      BMP/Smad signaling during embryonic dorsoventral pattern formation in zebrafish.

PMID- 22595676
TI  - miR-9 controls the timing of neurogenesis through the direct inhibition of
      antagonistic factors.
AB  - The timing of commitment and cell-cycle exit within progenitor populations during
      neurogenesis is a fundamental decision that impacts both the number and identity
      of neurons produced during development. We show here that microRNA-9 plays a key
      role in this process through the direct inhibition of targets with antagonistic
      functions. Across the ventricular zone of the developing zebrafish hindbrain, miR
      9 expression occurs at a range of commitment stages. Abrogating miR-9 function
      transiently delays cell-cycle exit, leading to the increased generation of late
      born neuronal populations. Target protection analyses in vivo identify the
      progenitor-promoting genes her6 and zic5 and the cell-cycle exit-promoting gene
      elavl3/HuC as sequential targets of miR-9 as neurogenesis proceeds. We propose
      that miR-9 activity generates an ambivalent progenitor state poised to respond to
      both progenitor maintenance and commitment cues, which may be necessary to adjust
      neuronal production to local extrinsic signals during late embryogenesis.

PMID- 22595678
TI  - pH-responsive nanovalves based on hollow mesoporous silica spheres for controlled
      release of corrosion inhibitor.
AB  - In the present study,  a new encapsulation technique for corrosion inhibitor is
      proposed. The hollow mesoporous silica spheres (HMSs) were synthesized by the co
      templates method as nanocontainers for corrosion inhibitor, benzotriazole (BTA)
      and the supramolecular nanovalves, consisting of cucurbit[6]uril (CB[6]) rings
      and the functional stalks attached to the surface of HMSs achieved on-demand
      release. The synthesis process of HMSs and the assembly process of the nanovalves
      were confirmed by SEM, TEM, N(2) adsorption/desorption, FTIR, TGA and solid-state
      (13)C CP/MAS NMR. The encapsulation capacity and release characteristics of BTA
      loaded, assembled HMSs were investigated. The HMSs assembled with the nanovalves
      possessed a higher encapsulation capacity for BTA than MCM-41 assembled under the
      same procedure due to its huge hollow internal structure. The pH-controlled
      release properties of BTA from the assembled HMSs under different pH environments
      were monitored by ultraviolet absorption spectra. The release profiles showed
      that there was almost no leakage of BTA from the assembled HMSs in neutral
      solution, while in alkaline solution BTA released very quickly, and the release
      rate increased with increasing pH values. Such a property makes the HMSs
      assembled with the pH-responsive nanovalves have great potential applications in
      smart anticorrosion coatings.

PMID- 22595679
TI  - Anisotropic interface induced formation of Sb nanowires on GaSb(111)A substrates.
AB  - The growth of Sb nanowires on GaSb(111)A substrates is studied by in situ
      azimuthal scan reflection high-energy electron diffraction (ARHEED). Bulk and
      layer contributions can be distinguished in the ARHEED transmission pattern
      through the Sb nanowires. The three-dimensional structure of the growing Sb
      nanowires is identified by post-growth atomic force microscopy (AFM) and x-ray
      diffraction (XRD). The lattice match of the Sb crystal along the [Formula: see
      text] and the GaSb crystal along [Formula: see text] directions lead to a
      preferential orientation of the Sb nanowires. The Sb adsorption and desorption
      kinetics is studied by thermal desorption spectroscopy.

PMID- 22595680
TI  - Evolving concepts in the management of drug resistant ovarian cancer: dose dense
      chemotherapy and the reversal of clinical platinum resistance.
AB  - Despite the initially high response rate to standard front-line debulking surgery
      followed by platinum-based chemotherapy, the relapse rate in ovarian cancer is
      high and many patients will recur within 6 months of completing platinum based
      treatment. These patients may still require further chemotherapy despite being
      considered "platinum resistant". In this setting, response rates to
      conventionally scheduled second line platinum and non-platinum agents is low,
      ranging between 5% and 15%. There is an emerging body of evidence that in this
      scenario, chemotherapeutic activity can be enhanced using unconventionally
      scheduled "dose-dense" platinum and non-platinum based regimens with improved
      response rates of up to 65%. Randomised studies to evaluate the impact of this
      approach on survival in recurrent, platinum resistant disease are urgently
      required to confirm the promising phase II findings if there is to be a change in
      the standard of care of patients with platinum resistant disease. In this review
      we discuss the evolving strategies to overcome resistance in patients with
      platinum resistant ovarian cancer with a particular focus on alterations in dose
      schedule as a means of reversing platinum resistance.

PMID- 22595681
TI  - Evaluation of the analytical sensitivity of a polymerase chain reaction assay for
      the detection of chicken infectious anemia virus in avian vaccines.
AB  - Chicken infectious anemia virus (CAV) is a ubiquitous pathogen of chickens
      causing significant disease in commercial flocks worldwide. During CAV outbreaks,
      the Center for Veterinary Biologics requires manufacturers of veterinary
      biologicals to test materials derived from infected flocks for extraneous CAV by
      polymerase chain reaction (PCR). The analytical sensitivity of a PCR assay for
      detection of CAV was determined and the applicability of a CAV DNA standard as a
      positive control for assay validity was evaluated. The analytical sensitivity of
      the CAV PCR assay was assessed to be 100 copies per reaction for the DNA standard
      and 1 * 101.9 TCID50/reaction for infectious virus. Establishing the analytical
      sensitivity of this CAV PCR assay and the inclusion of internal and external
      positive controls for validity provide a basis for determining whether suspect
      materials are safe for use in the production of veterinary biologics.

PMID- 22595682
TI  - Advanced cardiac life support: what's new, what's old?

PMID- 22595683
TI  - Emergency nurses' perception of department design as an obstacle to providing end
      of-life care.
AB  - INTRODUCTION: Of the 119.2 million visits to the emergency department in 2006, it
      was estimated that about 249,000 visits resulted in the patient dying or being
      pronounced dead on arrival. In 2 national studies of emergency nurses'
      perceptions of end-of-life (EOL) care, ED design was identified as a large and
      frequent obstacle to providing EOL care. The purpose of this study was to
      determine the impact of ED design on EOL care as perceived by emergency nurses
      and to determine how much input emergency nurses have on the design of their
      emergency department. METHODS: A 25-item questionnaire regarding ED design as it
      affects EOL care was sent to a national, geographically dispersed, random sample
      of 500 members of ENA. Inclusion criteria were nurses who could read English,
      worked in an emergency department, and had cared for at least one patient at the
      EOL. Descriptive statistics were calculated for the Likert-type and demographic
      items. Open-ended questions were analyzed using content analysis. RESULTS: Two
      mailings yielded 198 usable responses. Nurses did not report that ED design was
      as large an obstacle to EOL care as previous studies had suggested. Nurses
      reported that the ED design helped EOL care at a greater rate than it obstructed
      EOL care. Nurses also believed they had little input into unit design or layout
      changes. The most common request for design change was private places for family
      members to grieve. Thirteen nurses also responded with an optional drawing of
      suggested ED designs. DISCUSSION: Overall, nurses reported some dissatisfaction
      with ED design and believed they had little to no input in unit design
      improvement. Improvements to EOL care might be achieved if ED design suggestions
      from emergency nurses were considered by committees that oversee remodeling and
      construction of emergency departments. Further research is needed to determine
      the impact of ED design on EOL care in the emergency department.

PMID- 22595684
TI  - Moving an emergency department: lessons learned.

PMID- 22595685
TI  - How to manage the patient in the emergency department with a left ventricular
      assist device.

PMID- 22595687
TI  - Aging memories: differential decay of episodic memory components.
AB  - Some memories about events can persist for decades, even a lifetime. However,
      recent memories incorporate rich sensory information, including knowledge on the
      spatial and temporal ordering of event features, while old memories typically
      lack this "filmic" quality. We suggest that this apparent change in the nature of
      memories may reflect a preferential loss of hippocampus-dependent,
      configurational information over more cortically based memory components,
      including memory for individual objects. The current study systematically tests
      this hypothesis, using a new paradigm that allows the contemporaneous assessment
      of memory for objects, object pairings, and object-position conjunctions.
      Retention of each memory component was tested, at multiple intervals, up to 3 mo
      following encoding. The three memory subtasks adopted the same retrieval paradigm
      and were matched for initial difficulty. Results show differential decay of the
      tested episodic memory components, whereby memory for configurational aspects of
      a scene (objects' co-occurrence and object position) decays faster than memory
      for featured objects. Interestingly, memory requiring a visually detailed object
      representation decays at a similar rate as global object recognition, arguing
      against interpretations based on task difficulty and against the notion that
      (visual) detail is forgotten preferentially. These findings show that memories
      undergo qualitative changes as they age. More specifically, event memories become
      less configurational over time, preferentially losing some of the higher order
      associations that are dependent on the hippocampus for initial fast encoding.
      Implications for theories of long-term memory are discussed.

PMID- 22595688
TI  - Medial prefrontal cortex is selectively involved in response selection using
      visual context in the background.
AB  - The exact roles of the medial prefrontal cortex (mPFC) in conditional choice
      behavior are unknown and a visual contextual response selection task was used for
      examining the issue. Inactivation of the mPFC severely disrupted performance in
      the task. mPFC inactivations, however, did not disrupt the capability of
      perceptual discrimination for visual stimuli. Normal response selection was also
      observed when nonvisual cues were used as conditional stimuli. The results
      strongly suggest that the mPFC is not necessarily involved in the inhibition of
      response or flexible response selection in general, but is rather critical when
      response selection is required conditionally using visual context in the
      background.

PMID- 22595691
TI  - Cost utility analyses in international disaster responses-where are they?
AB  - International health care providers have flocked to Haiti and other disaster
      affected countries in record numbers. Anecdotal articles often give "body counts"
      to describe what was accomplished, followed months later by articles suggesting
      outcomes could have been better. Mention will be made that various interventions
      were "expensive," or not the best use of limited funds. But there is very little
      science to post-intervention evaluations, especially with regard to the value for
      the money spent. This is surprising, because a large body of literature exists
      with regard to the Cost Utility Analysis (CUA) of health care interventions.
      Applying reproducible metrics to disaster interventions will help improve
      performance.This study will: (1) introduce and explain basic CUA; (2) review why
      the application of CUA is difficult in disaster settings; (3) consider how
      disasters may be unique with regard to CUA; (4) demonstrate past and theoretical
      utilization of CUA in disaster settings; and (5) suggest future utilization of
      CUA by healthcare providers in Disaster Response.

PMID- 22595689
TI  - Critical analysis of renal duplex ultrasound parameters in detecting significant
      renal artery stenosis.
AB  - BACKGROUND: Several published studies have reported differing results of renal
      duplex ultrasound (RDU) imaging in detecting significant renal artery stenosis
      (RAS) using different Doppler parameters. This study is the largest to date to
      compare RDU imaging vs angiography and assess various published Doppler criteria.
      METHODS: RDU imaging and angiography were both done in 313 patients (606 renal
      arteries). RAS was classified as normal, <60%, >= 60% to 99%, and occlusion. Main
      outcome measurements included renal peak systolic velocity (PSV), systolic renal
      to-aortic ratio (RAR), end-diastolic velocity (EDV), and kidney lengths. RESULTS:
      The mean PSVs and RARs for normal, <60%, and >= 60% stenosis were 173, 236, and
      324 cm/s (P < .0001), and 2.2, 2.9, and 4.5, respectively (P < .0001). The PSV
      cutoff value that provided the best overall accuracy for >= 60% stenosis was 285
      cm/s, with a sensitivity, specificity, and overall accuracy of 67%, 90%, and 81%,
      respectively. The RAR cutoff value with the best overall accuracy for >= 60%
      stenosis was 3.7, with a sensitivity, specificity, and overall accuracy of 69%,
      91%, and 82%, respectively. A PSV of >= 180 cm/s and RAR of >= 3.5 had a
      sensitivity, specificity, and overall accuracy of 72%, 81%, and 78% in detecting
      >= 60% stenosis. A PSV of >= 200 cm/s with an RAR of >= 3.5 had a sensitivity,
      specificity, and overall accuracy of 72%, 83%, and 78% in detecting >= 60%
      stenosis. A receiver operator characteristic (ROC) curve analysis showed that the
      PSV and RAR were better than the EDV in detecting >= 60% stenosis: PSV area under
      the curve (AUC) was 0.85 (95% confidence interval [CI], 0.81-0.88), EDV AUC was
      0.71, and RAR AUC was 0.82 (PSV vs EDV, P < .0001; PSV vs RAR, P = .075; EDV vs
      RAR, P < .0001). A PSV of 285 cm/s or RAR of 3.7 alone were better than any
      combination of PSVs, EDVs, or RARs in detecting >= 60% stenosis. The mean kidney
      length was 10.4 cm in patients with >= 60% stenosis vs 11.0 cm in patients with
      <60% stenosis (P < .0001). Twelve percent of patients with >= 60% stenosis had a
      kidney length of <= 8.5 cm vs 4% in patients with <60% stenosis (P = .0003), and
      5.6% (34 of 606) had accessory renal arteries on angiography, with six detected
      on RDU imaging. The presence of accessory renal arteries, solitary kidneys, or
      renal fibromuscular dysplasia had no influence on overall accuracy of using PSV
      values for detecting >= 60% stenosis. CONCLUSIONS: A PSV of 285 cm/s or an RAR of
      3.7 alone can be used in detecting >= 60% RAS. Previously published data must be
      validated in individual vascular laboratories.

PMID- 22595693
TI  - HIV vaccine design: the neutralizing antibody conundrum.

PMID- 22595692
TI  - Plasticity and cross-talk of interleukin 6-type cytokines.
AB  - Interleukin (IL)-6-type cytokines are critically involved in health and disease.
      The duration and strength of IL-6-type cytokine-mediated signaling is tightly
      regulated to avoid overshooting activities. Here, molecular mechanisms of inter
      familiar cytokine cross-talk are reviewed which regulate dynamics and strength of
      IL-6 signal transduction. Both plasticity and cytokine cross-talk are
      significantly involved in pro- and anti-inflammatory/regenerative properties of
      IL-6-type cytokines. Furthermore, we focus on IL-6-type cytokine/cytokine
      receptor plasticity and cross-talk exemplified by the recently identified
      composite cytokines IL-30/IL-6R and IL-35, the first inter-familiar IL-6/IL-12
      family member. The complete understanding of the intra- and extracellular
      cytokine networks will aid to develop novel tailor-made therapeutic strategies
      with reduced side effects.

PMID- 22595694
TI  - Transcriptional control of innate lymphocyte fate decisions.
AB  - It has recently emerged that innate lymphocytes are more diverse than previously
      appreciated. In addition to natural killer cells, various subsets of innate
      lymphoid cells are now being characterized. It has become apparent that the
      transcriptional programs underlying lineage specification and cell fate decisions
      of innate lymphocytes strikingly resemble those of T cell subsets, suggesting
      that such transcriptional circuitry was already pre-formed in the evolutionary
      older innate immune system. Here, we will review recent advances in our
      understanding of the core transcriptional programs driving development and cell
      fate decisions of innate lymphocytes. We will also discuss whether these
      transcriptional programs are stable or flexible, thereby allowing for plastic
      adaptation of immune responses.

PMID- 22595695
TI  - Trends in hepatitis B and hepatitis C virus seropositivity among blood donors
      over 15 years screened in the blood bank of a university hospital.
AB  - Blood transfusion carries well defined risks including hepatitis B and hepatitis
      C virus transmission. In this study, records of blood donation candidates between
      the years 1996-2010 were retrospectively reviewed. A total of 220 841 apparently
      healthy adult donors were screened for hepatitis B surface antigen, anti-HCV with
      enzyme linked immunosorbent assay (ELISA) method. The overall prevalence of HbsAg
      and HCV were 1.07% and 0.39%, respectively. HBV seroprevelance decreased through
      years 1996-2010 but HCV seroprevelance showed a fluctuant course decreasing from
      1996 to 2002. In order to decrease transfusion transmitted infections there
      should be centralized blood collection systems having qualified staff, equipment
      and non-remunerated voluntary blood donations must be strongly encouraged.

PMID- 22595696
TI  - The effect of pneumatic tube system on complete blood count parameters and
      thrombocyte donation in healthy donors.
AB  - This paper is the first report whether or not pneumatic tube system affects the
      selection of apheresis donors according to the results of complete blood count.
      According to the apheresis guidelines, hemoglobin level must be >=12.5g/dL and
      platelet level >=150/MUL to be a donor. Paired blood samples of 26 healthy
      volunteers were transported by either hand delivered or a pneumatic tube system
      to the laboratory. No statistically significant differences were observed in
      order to mean values of routine complete blood cell count and white cell
      differential parameters that were send for selection of apheresis donor before
      the procedure. Therefore, all healthy volunteers decided as a donor according to
      the laboratory results independent from transport method.

PMID- 22595697
TI  - Electrostatic force microscopy as a broadly applicable method for characterizing
      pyroelectric materials.
AB  - A general method based on the combination of electrostatic force microscopy with
      thermal cycling of the substrate holder is presented for direct, nanoscale
      characterization of the pyroelectric effect in a range of materials and sample
      configurations using commercial atomic force microscope systems. To provide an
      example of its broad applicability, the technique was applied to the examination
      of natural tourmaline gemstones. The method was validated using thermal cycles
      similar to those experienced in ambient conditions, where the induced
      pyroelectric response produced localized electrostatic surface charges whose
      magnitude demonstrated a correlation with the iron content and heat dissipation
      of each gemstone variety. In addition, the surface charge was shown to persist
      even at thermal equilibrium. This behavior is attributed to constant, stochastic
      cooling of the gemstone surface through turbulent contact with the surrounding
      air and indicates a potential utility for energy harvesting in applications
      including environmental sensors and personal electronics. In contrast to
      previously reported methods, ours has a capacity to carry out such precise
      nanoscale measurements with little or no restriction on the sample of interest,
      and represents a powerful new tool for the characterization of pyroelectric
      materials and devices.

PMID- 22595698
TI  - Age-related expression, enzymatic solubility and modification with advanced
      glycation end-products of fibrillar collagens in mouse lung.
AB  - Changes in the expression of fibrillar collagens and post-translational
      modifications with advanced glycation end-products (AGEs) are often associated
      with tissue aging. Less is known about age-related changes in mouse lung tissue.
      Therefore, we studied the expression level and AGE load of fibrillar collagens in
      lungs from young (<=6 months), adult (15 months) and old (>=25 months) mice. The
      mRNA expression level was reduced in adult and old mice compared with the young.
      Old mice also showed a reduced protein level, whereas the adults even had more
      collagen protein. Fractionating of the fibrillar collagens into enzyme-soluble
      and insoluble collagens revealed a reduced solubility of collagens in old age.
      The enzymatic solubility of fibrillar collagens correlated inversely with the AGE
      load in the insoluble collagen as detected by the AGE-related fluorescence. While
      the intensity of the AGE-related fluorescence was increased in fibrillar
      collagens in response to age, the fluorescing AGE variant argpyrimidine was less
      affected. In summary, aging causes a reduced expression, lower enzymatic
      solubility and increased AGE load of fibrillar collagens in mouse lung tissue,
      but not all changes occur gradually with age.

PMID- 22595699
TI  - From the womb to the tomb: the role of transfers in shaping the evolved human
      life history.
AB  - Humans are the longest living and slowest growing of all primates. Although most
      primates are social, humans are highly cooperative and social in ways that likely
      co-evolved with the slow human life history. In this paper we highlight the role
      of resource transfers and non-material assistance within and across generations
      in shaping low human mortality rates. The use of complex cooperative strategies
      to minimize risk is a necessary precursor for selecting further reductions in
      mortality rate in late adulthood. In conjunction with changes in the age-profile
      of production, the impacts of resource transfers and other forms of cooperation
      on reducing mortality likely played an important role in selection on post
      reproductive lifespan throughout human evolution. Using medical data and
      ethnographic interviews, we explore several types of common risks experienced by
      Tsimane forager-horticulturalists, and quantify the types and targets of aid. Our
      results illustrate the importance of transfers in several key domains and suggest
      that the absence of transfers would greatly increase human mortality rates
      throughout the life course.

PMID- 22595700
TI  - Association of serum uric acid with body mass index among long-lived Chinese.
AB  - OBJECTIVES: To examine the individual association between BMI and level of serum
      uric acid (SUA) among the very elderly Chinese population. METHODS: A survey was
      conducted on 870 long-lived subjects (aged >=90years). Subjects were divided into
      four groups according to quartile of BMI (<16.6, 16.6-18.9, 18.9-21.1,
      >=21.1kg/m(2)) and to classification criteria of underweight, normal weight,
      overweight and obesity in BMI (<18.5, 18.5-23.0, 23.0-27.5, >=27.5kg/m(2),
      respectively). Subjects were also divided into hyperuricemia and normal SUA
      groups. RESULTS: The sample included 661 unrelated Chinese. The mean age was
      93.52+/-3.29years (range 90-108years). The mean level of BMI was 19.16+/
      3.47kg/m(2) and mean SUA was 318.72+/-87.01. Compared to individuals without
      hyperuricemia, high level of SUA was associated with a higher level of BMI in
      both genders (p<0.001). According to the both BMI classification criteria, the
      group with higher BMI had higher level of SUA (p<0.001). Pearson correlation
      showed that SUA was significantly correlated with BMI (with coefficients r=0.235,
      0.140, in men and women, respectively). Unadjusted and adjusted multiple logistic
      regressions showed that odds ratios for hyperuricemia were associated with BMI
      according to quartile of BMI. CONCLUSIONS: We found that among long-lived Chinese
      subjects, higher levels of SUA may be associated with higher BMI.

PMID- 22595701
TI  - Biomechanical and metabolic responses to seat-tube angle variation during cycling
      in tri-athletes.
AB  - One of the most physically demanding parts of triathlon is the transition from
      cycling to running. Many tri-athletes believe that increasing seat-tube angle
      (STA) can bring advantages in the following running part. The aim of this study
      was to evaluate the effects of inverting the support of the seat, for increasing
      STA, on the metabolic response and on the muscle activation pattern, maintaining
      a controlled kinematic. Moreover, a muscle-skeletal model was applied to evaluate
      the hypothesis that increasing STA changes force-producing capabilities of
      muscles crossing the hip. Ten tri-athletes cycled at two different power levels
      and with two different STA's. Gas exchange data, kinematics and surface
      electromyography (sEMG) were acquired during the tests. sEMG was measured from
      eight muscles of the right side of the body. A model of muscle mechanics and
      energy expenditure was applied to estimate variations of force production
      capabilities and muscle energy consumption between the two STA configurations.
      Inverting the support of the seat showed no significant effects on kinematic,
      Oxygen consumption, muscle activations and muscle power production capabilities.
      Nevertheless, an interesting advantage can be the tendency to less activate
      gastrocnemius and biceps femoris: this could lead to minor muscle fatigue during
      the following running phase.

PMID- 22595702
TI  - Altered preparatory pelvic control during the sit-to-stance-to-sit movement in
      people with non-specific low back pain.
AB  - People with non-specific low back pain (LBP) show hampered performance of dynamic
      tasks such as sit-to-stance-to-sit movement. However, the underlying mechanisms
      remain obscure. Therefore, the aim of this study was to assess if proprioceptive
      impairments influence the performance of the sit-to-stance-to-sit movement.
      First, the proprioceptive steering of 20 healthy subjects and 106 persons with
      mild LBP was identified during standing using muscle vibration. Second, five sit
      to-stance-to-sit repetitions on a stable support and on foam were performed as
      fast as possible. Total duration, phase duration, center of pressure (COP)
      displacement, pelvic and thoracic kinematics were analyzed. People with LBP used
      less lumbar proprioceptive afference for postural control compared to healthy
      people (P < 0.0001) and needed more time to perform the five repetitions in both
      postural conditions (P < 0.05). These time differences were determined in the
      stance and sit phases (transition phases), but not in the focal movement phases.
      Moreover, later onsets of anterior pelvic rotation initiation were recorded to
      start both movement sequences (P < 0.05) and to move from sit-to-stance on foam
      (P < 0.05). Decreased use of lumbar proprioceptive afference in people with LBP
      seemed to have a negative influence on the sit-to-stance-to-sit performance and
      more specifically on the transition phases which demand more control (i.e. sit
      and stance). Furthermore, slower onsets to initiate the pelvis rotation to move
      from sit-to-stance illustrate a decrease in pelvic preparatory movement in the
      LBP group.

PMID- 22595703
TI  - Site-selective assembly of quantum dots on patterned self-assembled monolayers
      fabricated by laser direct-writing.
AB  - A simple and efficient route for quantum dot (QDs) patterning using self
      assembled monolayers (SAMs) as templates is described. By means of a laser direct
      writing (LDW) technique, SAMs of octadecylphosphonic acid formed by adsorption on
      native oxide layer of titanium film were patterned through laser-induced ablation
      of the SAM molecules. This technique allows the creation of chemical-specific
      patterns accompanied by slight change in the topography. Using atomic force
      microscopy and friction force microscopy, the dependence of feature size and
      characteristics on the irradiation dose was demonstrated. Upon immersion of a
      substrate with patterned SAMs bearing thiol as the terminal group into a
      dispersion of QDs resulted in the assembly of QDs on the specific thiol
      terminated areas. Patterns of QDs with different photoluminescent wavelength were
      generated. The LDW technique, which is convenient and flexible due to its path
      directed and maskless fabrication process, provided a new powerful approach for
      patterning materials on surfaces for various applications.

PMID- 22595704
TI  - Pain management in the pediatric surgical patient.
AB  - Surgeons performing painful, invasive procedures in pediatric patients must be
      cognizant of both the potential short- and long-term detrimental effects of
      inadequate analgesia. This article reviews the available tools, sedation
      procedures, the management of intraoperative, postoperative, and postprocedural
      pain, and the issues surrounding neonatal addiction.

PMID- 22595705
TI  - Pediatric inguinal hernias, hydroceles, and undescended testicles.
AB  - Pediatric inguinal hernias are extremely common, and can usually be diagnosed by
      simple history taking and physical examination. Repair is elective, unless there
      is incarceration or strangulation. Hydroceles are also quite common, and in
      infancy many will resolve without operative intervention. Undescended testicles
      harbor an increased risk of infertility and malignancy, and require orchiopexy in
      early childhood.

PMID- 22595706
TI  - Diagnosis and management of pediatric appendicitis, intussusception, and Meckel
      diverticulum.
AB  - Three of the most common causes of surgical abdominal pain in pediatric patients
      include appendicitis, Meckel diverticulum, and intussusception. All 3 can present
      with right lower quadrant pain, and can lead to significant morbidity and even
      mortality. Although ultrasound is the preferred method of diagnosis with
      appendicitis and intussusception, considerable variety exists in the modalities
      needed in the diagnosis of Meckel diverticulum. This article discusses the
      pathways to diagnosis, the modes of treatment, and the continued areas of
      controversy.

PMID- 22595707
TI  - Pyloric stenosis in pediatric surgery: an evidence-based review.
AB  - Pyloric stenosis is a common pediatric surgical problem that requires a
      combination of both medical and surgical attention. This article reviews the
      classical elements necessary to care for the patient in a safe and effective
      manner. A well-tested management approach that can be applied to the general
      surgical environment is described. Perioperative management of the patient is
      discussed and the currently used techniques are reviewed. Current recommendations
      include the routine use of ultrasonography for diagnosis, attention to the
      preoperative correction of electrolytes, and the use of minimally invasive
      techniques for treatment.

PMID- 22595708
TI  - Pediatric gastroesophageal reflux disease.
AB  - This article reviews the mechanisms responsible for gastroesophageal reflux
      disease (GERD), available techniques for diagnosis, and current medical
      management. In addition, it extensively discusses the surgical treatment of GERD,
      emphasizing the use of minimally invasive techniques.

PMID- 22595709
TI  - Pediatric obesity.
AB  - Childhood obesity is a tremendous burden for children, their families, and
      society. Obesity prevention remains the ultimate goal but rapid development and
      deployment of effective nonsurgical treatment options is not currently achievable
      given the complexity of this disease. Surgical options for adolescent obesity
      have been proven to be safe and effective and should be offered. The development
      of stratified protocols of increasing intensity should be individualized for
      patients based on their disease severity and risk factors. These protocols should
      be offered in multidisciplinary, cooperative clinical trials to critically
      evaluate and develop optimal treatment strategies for morbid obesity.

PMID- 22595710
TI  - Congenital cervical cysts, sinuses, and fistulae in pediatric surgery.
AB  - Congenital cervical anomalies are essential to consider in the clinical
      assessment of head and neck masses in children and adults. These lesions can
      present as palpable cystic masses, infected masses, draining sinuses, or
      fistulae. Thyroglossal duct cysts are most common, followed by branchial cleft
      anomalies and dermoid cysts. Other lesions reviewed include median ectopic
      thyroid, cervical teratomas, and midline cervical clefts. Appropriate diagnosis
      and management of these lesions requires a thorough understanding of their
      embryology and anatomy. Correct diagnosis, resolution of infectious issues before
      definitive therapy, and complete surgical excision are imperative in the
      prevention of recurrence.

PMID- 22595711
TI  - Teratomas and ovarian lesions in children.
AB  - Ovarian pathology in children is common and the pathology can be quite diverse.
      The most common benign ovarian tumor in childhood is a teratoma. In this article,
      we discuss the origin of these germ cell tumors followed by a complete discussion
      of ovarian pathology.

PMID- 22595712
TI  - Pediatric chest I: Developmental and physiologic conditions for the surgeon.
AB  - This article addresses basic anatomic considerations of the chest and describes
      common conditions of the lungs, pleura, and mediastinum that affect children.

PMID- 22595713
TI  - Pediatric chest II: Benign tumors and cysts.
AB  - Thoracic tumors are rare in children, and metastatic or malignant conditions must
      be excluded during the diagnostic evaluation. The majority of primary pulmonary
      neoplasms in children are malignant; this article primarily addresses benign
      tumors. Surgical resection is the standard treatment for benign thoracic tumors
      in children. Thoracotomy is a traditional approach, but the thoracoscopic
      technique for diagnosis and treatment of thoracic tumors is well established. The
      term benign tumors can be a misnomer in that although their histology is not
      malignant, these tumors can be locally aggressive with significant associated
      morbidity and potential for mortality.

PMID- 22595714
TI  - Congenital diaphragmatic hernia and protective ventilation strategies in
      pediatric surgery.
AB  - Infants affected with congenital diaphragmatic hernias (CDH) suffer from some
      degree of respiratory insufficiency arising from a combination of pulmonary
      hypoplasia and pulmonary hypertension. Respiratory care strategies to optimize
      blood gasses lead to significant barotrauma, increased morbidity, and overuse of
      extracorporeal membrane oxygenation (ECMO). Newer permissive
      hypercapnia/spontaneous ventilation protocols geared to accept moderate
      hypercapnia at lower peak airway pressures have led to improved outcomes. High
      frequency oscillatory ventilation can be used in infants who continue to have
      persistent respiratory distress despite conventional ventilation. ECMO can be
      used successfully as a resuscitative strategy to minimize further barotrauma in
      carefully selected patients.

PMID- 22595716
TI  - Neonatal bowel obstruction.
AB  - Newborn intestinal obstructions are a common reason for admission to neonatal
      ICUs. The incidence is estimated to be approximately 1 in 2000 live births. There
      are 4 cardinal signs of intestinal obstruction in newborns: (1) maternal
      polyhydramnios, (2) bilious emesis, (3) failure to pass meconium in the first day
      of life, and (4) abdominal distention. The presentation may vary from subtle and
      easily overlooked findings on physical examination to massive abdominal
      distention with respiratory distress and cardiovascular collapse. A careful
      history and physical examination often identify the diagnosis. Concomitant
      resuscitation (volume, gastric decompression, and ventilatory support) may be
      necessary.

PMID- 22595715
TI  - Chest wall deformities in pediatric surgery.
AB  - Chest wall deformities can be divided into 2 main categories, congenital and
      acquired. Congenital chest wall deformities may present any time between birth
      and early adolescence. Acquired chest wall deformities typically follow prior
      chest surgery or a posterolateral diaphragmatic hernia repair (Bochdalek). The
      most common chest wall deformities are congenital pectus excavatum (88%) and
      pectus carinatum (5%). This article addresses the etiology, pathophysiology,
      clinical evaluation, diagnosis, and management of these deformities.

PMID- 22595717
TI  - Congenital abdominal wall defects and reconstruction in pediatric surgery:
      gastroschisis and omphalocele.
AB  - The embryology, epidemiology, associated anomalies, prenatal course and the
      neonatal and surgical care of newborns with gastroschisis and omphalocele are
      reviewed. For gastroschisis temporary intestinal coverage is often done before a
      more definitive operative closure that may be immediate or delayed. Outcomes in
      gastroschisis are determined by associated bowel injury. For omphalocele small
      defects are closed primarily while large defects are treated topically to allow
      initial skin coverage before a later definitive closure. Outcomes for omphalocele
      are determined mainly by the presence of associated anomalies.

PMID- 22595718
TI  - Pediatric intestinal failure and vascular access.
AB  - Emerging developments in the care of intestinal failure (IF) patients have
      drastically improved their overall prognosis, with recently reported survival
      rates over 90%. IF patients remain an extremely complex population who benefit
      from specialized, multidisciplinary care. Advances in the provision of parenteral
      and enteral nutrition, progress in the management of IF-associated liver disease
      with parenteral fish oil and catheter-associated blood stream infection with
      ethanol lock therapy, and the availability of novel surgical interventions, such
      as the serial transverse enteroplasty procedure, have made this a dynamic health
      care field with the promise of ongoing improvements in outcomes for these
      patients.

PMID- 22595719
TI  - Pediatric malignancies: neuroblastoma, Wilm's tumor, hepatoblastoma,
      rhabdomyosarcoma, and sacroccygeal teratoma.
AB  - Common pediatric malignancies are reviewed: neuroblastoma, Wilms tumor,
      hepatoblastoma, rhabdomyosarcoma, and sacrococcygeal teratoma. Elements of
      presentation, diagnosis, staging, treatment, and longterm prognosis are
      discussed, with particular attention to surgical management.

PMID- 22595720
TI  - Vascular anomalies in pediatrics.
AB  - Vascular tumors consist of lesions secondary to endothelial hyperplasia,
      incorporating both hemangiomas and less common pediatric vascular tumors.
      Vascular malformations arise by dysmorphogenesis and exhibit normal endothelial
      cell turnover. Some anomalies may incorporate multiple areas of the vascular
      tree. Use of this division has provided a clinically useful method of diagnosis
      and prognosis, as well as a guide to therapy. It is hoped that with continued
      investigation into the biology and pathogenesis of these lesions, a more
      comprehensive molecular classification will soon be developed.

PMID- 22595721
TI  - Pediatric surgery.

PMID- 22595722
TI  - Pediatric surgery.

PMID- 22595723
TI  - Spatial distributions of 137Cs in surface soil in Jing-Jin-Ji Region, North
      China.
AB  - Artificial Radiocaesium ((137)Cs) has been widely deposited over global soils. In
      this study, we measured (137)Cs activity concentrations in the soil samples taken
      from Jing-Jin-Ji Region, North China, during 2007-2008. The surface soil (0-20
      cm) samples were collected from 452 sites in this region. The activity
      concentration of (137)Cs in the samples was measured using a GEM series HPGe
      (high-purity germanium) coaxial detector system (ADCOM-100). The main findings
      are as following. (1) The activity concentration of (137)Cs in surface soils in
      the region of study fluctuates within 0.3+/-0.1 to 12.9+/-0.4 Bq/kg with mean
      value of 3.7 Bq/kg. Compared to other regions located at roughly the same
      latitude, the (137)Cs activity is relatively low. The results indicate that there
      are no new inputs of the radionuclides into the area at that time and the data
      obtained could serve as baseline levels of (137)Cs in Jing-Jin-Ji Region. (2)
      Considering land use types, surface soil in woodland mostly shows high (137)Cs
      activities with rare natural erosion and anthropogenic activities, and the
      surface soil with relatively low (137)Cs activities appears in the areas of
      intensive anthropogenic activities, especially in the cities, river banks,
      reservoirs and the strongly eroded areas. The findings suggest that the varying
      distribution of (137)Cs activities in surface soil corresponds with land use
      types.

PMID- 22595724
TI  - Direct uranium isotope ratio analysis of single micrometer-sized glass particles.
AB  - We present the application of nanosecond laser ablation (LA) coupled to a 'Nu
      Plasma HR' multi collector inductively coupled plasma mass spectrometer (MC-ICP
      MS) for the direct analysis of U isotope ratios in single, 10-20 MUm-sized, U
      doped glass particles. Method development included studies with respect to (1)
      external correction of the measured U isotope ratios in glass particles, (2) the
      applied laser ablation carrier gas (i.e. Ar versus He) and (3) the accurate
      determination of lower abundant (236)U/(238)U isotope ratios (i.e. 10(-5)). In
      addition, a data processing procedure was developed for evaluation of transient
      signals, which is of potential use for routine application of the developed
      method. We demonstrate that the developed method is reliable and well suited for
      determining U isotope ratios of individual particles. Analyses of twenty-eight S1
      glass particles, measured under optimized conditions, yielded average biases of
      less than 0.6% from the certified values for (234)U/(238)U and (235)U/(238)U
      ratios. Experimental results obtained for (236)U/(238)U isotope ratios deviated
      by less than -2.5% from the certified values. Expanded relative total combined
      standard uncertainties U(c) (k = 2) of 2.6%, 1.4% and 5.8% were calculated for
      (234)U/(238)U, (235)U/(238)U and (236)U/(238)U, respectively.

PMID- 22595725
TI  - [Laparoscopic appendectomy. Our experience].
AB  - The advantages and applications of the videolaparoscopic technique (VL) versus
      open surgery in the treatment of acute and complicated appendicitis are not well
      defined. Our study examined 150 patients, 67 males and 83 females. They underwent
      surgery for acute appendicitis in emergency. The choice between open or
      laparoscopic tecnique was due to patient's clinical conditions and surgeon's
      experience. Two of these patients had no infiammatory process. Eleven patients
      were affected by gynaecological diseases. The last 137 patients underwent surgery
      for acute appendicitis and the diagnosis was confirmed. Among them, 35 (25%) were
      affected by a complicated appendicitis with diffuse or clearly defined
      peritonitis. In 134 patients the surgery was completed laparoscopically. The
      conversion rate was 2%. Morbility rate was 3%, due to intra abdominal abscesses
      secondary to acute complicated appendicitis. The mean operative time was 76 min
      and the mean hospital stay was 4.8 days. The death rate was 0%. In our
      experience, laparoscopic appendectomy has significant advantages over traditional
      open surgery in both acute and complicated appendicitis, especially in young
      women. In this way, we can diagnose pelvic disease that could be characterized by
      the same symptoms of acute appendicitis, then we suggest laparoscopic
      appendectomy even just to complete the diagnostic iter. Laparoscopy is useful in
      terms of convalescence, postoperative pain, hospital stay, aesthetic outcome and
      an easier exploration of the peritoneal cavity.

PMID- 22595726
TI  - Update on gastric cancer. Introduction.

PMID- 22595727
TI  - Gastric cancer carcinogenesis and tumor progression.
AB  - BACKGROUND: Gastric cancer (GC) remains one of the leading causes of cancer
      related deaths worldwide, even though a decline has been observed in its
      incidence and the mortality rate in recent decades. Gastric carcinogenesis is a
      complex phenomena involving multiple epigenetic and genetic factors; several
      genetic, environmental and infectious agents interact causing a cumulative effect
      in the early steps of gastric carcinogenesis. MATERIALS AND METHODS: The most
      commonly used classifications of GC are the World Health Organization (WHO) and
      the Lauren classifications which describes two main histological types, diffuse
      and intestinal, which have different clinicopathological characteristics. Diffuse
      cancer occurs more commonly in young patients, can be multifocal, is not often
      accompanied by intestinal metaplasia and can be hereditary, in which E-cadherin
      alteration plays a pivotal role. Intestinal type is more frequently observed in
      older patients and follows multifocal atrophic gastritis. This is usually
      accompanied by intestinal metaplasia and leads to cancer via dysplasia, and thus
      intestinal metaplasia is considered a dependable morphological marker for GC
      risk. Intestinal adenocarcinoma predominates in the high-risk areas whereas the
      diffuse adenocarcinoma is more common in low-risk areas. DISCUSSION: Classically,
      genetic instability and Helicobater pylori (H. Pylori) infection are often
      identified in intestinal GC. The great majority of GCs are sporadic and result
      from the cumulative effects of different environmental risk factors; smoking,
      alcohol consumption and dietary habits have been addressed as significant. H.
      Pylori infection and proinflammatory cytokine gene polymorphisms represent other
      features of this compound process that leads to the development of GC. Other
      molecular pathway well described in GC is microsatellite instability (MSI) that
      related with specific clinic-pathological features. CONCLUSION: In this review we
      focused on the role of H. Pylori infection, MSI and alterations of CDH1 (E
      Cadherin) gene.

PMID- 22595728
TI  - Familial gastric cancer and germline mutations of E-cadherin.
AB  - BACKGROUND: Most gastric cancer (GC) is sporadic and seem to be mostly related to
      a cumulative effect of multiple environmental factors. Although the actual
      importance of genetic factors has not yet been fully documented, GC with familial
      aggregation has been found to have an incidence of 10% to 30%. MATERIALS AND
      METHODS: Genetic factors contribute to the well-known autosomal dominant syndrome
      defined as hereditary diffuse gastric cancer (HDGC) which can be related to
      germline mutations of the gene encoding E-cadherin gene (CDH1). It has been
      estimated that 1-3% of cases of GC are due to HDGC. DISCUSSION AND CONCLUSION:
      The authors review data on CDH1 mutations in HDGC ,CDH1 testing criteria, and
      treatment. They conclude that cancer pedigrees and screening for CDH1 mutations
      are essential for improving the management of this disease.

PMID- 22595729
TI  - Early gastric cancer: detection and endoscopic treatment.
AB  - BACKGROUND: Early Gastric Cancer (EGC) is defined as a neoplasm confined to the
      mucosa or submucosa regardless of regional lymph node metastasis. The rate of
      EGC, which varies by country, is up to 40-60% of all gastric cancer cases in
      Japan, whilst in Western countries, the proportion remains at 5-10%. There is a
      strong male predominance in EGC. The average 5-year survival rate of patients
      with EGC reached over 90% in Japanese and European data. MATERIALS AND METHODS:
      Many EGC patients present with symptoms suggestive of a benign gastric ulcers.
      The combination of serum pepsinogen and Helicobacter pylori status may provide
      even more sensitive information for screening. However high-quality endoscopic
      evaluation with biopsy is the key to diagnosis. To improve the quality of
      observation several endoscopic imaging modalities have been developed for the
      diagnosis of early gastric cancer. Endoscopic resection is a viable alternative
      to surgery for curative treatment of EGC, with similar long term results.
      Endoscopic mucosal resection (EMR) of EGC without any risk of lymph node
      metastasis was developed in Japan in the 1980s, and it has been one of the
      standard treatments of EGC for nearly 20 years. Recently, several EMR techniques
      developed in Japan have been accepted and done in Western countries. These EMR
      techniques are safe and efficacious but unsuitable for large lesions. DISCUSSION:
      Because we could not remove a large lesion in 1 fragment, which was very
      important for the precise diagnosis of tumor depth, local recurrence increased in
      large-lesion cases. An innovative procedure using newly developed endoscopic
      knives, called endoscopic submucosal dissection (ESD), was developed in the late
      1990s, which made it possible to remove a large lesion en bloc. CONCLUSION:
      Theoretically, ESD has no limitation with respect to tumor size; therefore, it is
      expected to replace the surgical treatment in some situations. Although ESD has
      spread throughout Japan within a short period, there remain several
      disadvantages, such as a higher incidence of complications and a requirement of
      higher endoscopic skills compared to those of conventional EMR methods.

PMID- 22595730
TI  - Laparoscopic and mini-invasive surgery.
AB  - BACKGROUND: JGCA Gastric Cancer Treatment Guidelines (2004) include Laparoscopic
      Assisted Distal Gastrectomy (LADG) within the chapter of modified surgery. A
      metanalysis published in 2010 shows that LADG is significantly superior to Open
      Distal Gastrectomy (ODG) if comparing short term outcomes. Oncologic results
      prove to be comparable to ODG by one RCT and 2 retrospective studies. Little
      evidence is available on Laparoscopic Total Gastrectomy and concerns are raised
      about long-term oncologic outcomes. MATERIALS AND METHODS: Laparoscopic Subtotal
      Gastrectomy is carried out with 4 to 5 ports in the periumbilical region (Hasson
      trocar for laparoscope) and upper quadrants. After exploration of the abdominal
      cavity surgical steps include coloepiploic detachment, omentectomy, dissection of
      the gastrocolic ligament, division of the left gastroepiploic vessels, division
      of right gastroepiploic vessels, division of pyloric vessels. The duodenum is
      transected with a linear stapler. Incision of the lesser omentum and dissection
      of the hepatoduodenal ligament allows completion of D2 lymphadenectomy. The
      4/5ths of the stomach are transected starting from the greater curve at the
      junction of left and right gastroepiploic arcades by linear stapler. Roux-en-Y
      loop reconstruction is performed through a stapled side-to-side gastro-jejunal
      anastomosis and a side-to-side jejuno-jejunal anastomosis. Reconstruction after
      Laparoscopic Total Gastrectomy is performed preferably by a side-to-side esophago
      jejunal anastomosis according to Orringer. DISCUSSION AND CONCLUSION: A robotic
      assisted approach adds precision on lymphadenectomy and reconstructive
      techniques.

PMID- 22595731
TI  - Lymphadenectomy for gastric cancer: still a matter of debate?
AB  - BACKGROUND: For more than a century the extent of surgical treatment of gastric
      cancer is a matter of debate. Through experience, evaluation and research, the
      outcome of gastric cancer has improved. Many aspects are of influence of outcome,
      but only a radical resection can offer long-term outcomes. In this review, we
      will discuss the history and current status of the extent of lymph node
      dissection. MATERIALS AND METHODS: Some issues about the extent of gastric
      resection seem to have been settled. For survival it is not necessary to perform
      a total gastrectomy if free resection margins can be obtained with a subtotal
      gastrectomy. In the context of postoperative morbidity and mortality a subtotal
      gastrectomy is to be preferred. Microscopic resection line involvement has shown
      to be of great influence on prognosis. DISCUSSION: At this moment the main
      discussion centres around the extent of lymph node dissection, locoregional
      recurrence and to the influence of additional treatment. For many years it has
      been debated whether an extended lymph node dissection for gastric cancer is
      beneficial. Theoretically, removal of a wider range of lymph nodes by extended
      lymph node dissection increases the chances for cure. Such resection, however,
      may be irrelevant if there are no lymph nodes affected or if the cancer has
      developed into a systemic disease, or if it increases morbidity and mortality
      substantially. CONCLUSION: Relapse after curative surgery because of local
      recurrence or regional lymph node metastasis have been shown in up to 87.5% of
      patients. The extent of surgery, however, may be of influence on the locoregional
      recurrence rate.

PMID- 22595732
TI  - Treatment of esophago-gastric junction adenocarcinoma.
AB  - AIM: The incidence of Adenocarcinoma of the esophagogastric junction (EGJ) is
      increasing and its treatment is still debated, primarily because of the non
      uniform definition of EGJ. MATERIALS AND METHODS: The most used classification of
      EGJ cancer was proposed by Siewert and it divides the EGJ in three regions: from
      5 to 1 cm above the Z line (Siewert type I or esophageal Adenocarcinoma), from 1
      over to 2 below the Z line (Siewert type II or real Cardia cancer) and from 2
      below to 5 below the Z line (Siewert type III or proximal Gastric cancer diffused
      to Cardia). The neoplasia is defined type I, II or III depending on where is the
      center of the cancer. DISCUSSION: This classification did not show to be related
      to differences in prognosis and survival, but it has been used to guide the
      surgical strategy based on the site of the tumor. Criticism about this
      classification focuses mainly on the non-uniform treatment, in the current
      literature, of Siewert Type II cancer. CONCLUSION: From January 2010, a new
      definition of EGJ carcinoma has been introduced by TNM. This new definition
      considers esophageal cancers all the ones whose centers falls inside a line drawn
      5 cm below the Z line with invasion of the esophagus. This means that Siewert
      type I and II are now considered esophageal cancers, while type III can be
      esophageal or proximal gastric cancer depending if the esophagus is infiltrated
      or not. Criticism about this new definition rises on the border-line definition
      of former Siewert type III cancers.

PMID- 22595733
TI  - Neoadjuvant chemotherapy and ongoing-trials.
AB  - AIM: The history of preoperative therapy for gastric carcinoma was outlined here
      to demonstrate its value in terms of safety and efficacy. MATERIAL OF STUDY: The
      data collected in this review were obtained from studies found in PubMed using
      the search terms "preoperative chemotherapy",  "preoperative radiotherapy",
      "preoperative chemoradiotherapy", "neoadjuvant treatment", and "gastric cancer".
      Only papers published in English language between January 1970 and January 2010
      were selected. RESULTS: Studies conducted over the last twenty years have
      progressed from the first "pioneering" chemotherapies for patients with non
      resectable disease ("induction" therapy) to the most recent phase III trials of a
      "neoadjuvant" therapy for resectable gastric neoplasms. DISCUSSION: Several
      clinical trials of pre-operative chemotherapy in the management of gastric cancer
      have been attempted. Despite needing further data regarding the definitive role
      of neoadjuvant therapy, the results of preoperative chemotherapy in the
      multimodal treatment of gastric adenocarcinoma are encouraging since the
      treatment increase the likelihood that a truly "curative" (R0) delayed surgical
      procedure can be achieved. Owing to the results of last randomized phase III
      studies, neoadjuvant chemotherapy for locally advanced resectable gastric cancer
      has become a level I evidence.

PMID- 22595734
TI  - The role of intraperitoneal chemotherapy in the treatment of patients with
      advanced gastric cancer.
AB  - AIM: To review the published literature analyzing the role of intraperitoneal
      chemotherapy in gastric cancer. MATERIAL OF STUDY: Peritoneal dissemination is a
      well recognized and important component of disease progression in gastric cancer.
      Considering that involvement of the peritoneal surface can be anticipated in a
      large number of patients who present with an advanced gastric cancer, research
      efforts have been focusing not only on treatment of established peritoneal
      disease but also on prevention of peritoneal dissemination during surgery for
      primary gastric cancer. RESULTS: The pharmacologic rationale for intraperitoneal
      chemotherapy has been well studied. The role and results of HIPEC combined with
      cytoreductive surgery for patients with established carcinomatosis from gastric
      cancer has been reported by several groups and appears to be a promising modality
      for a selected group of patients with limited disease. DISCUSSION: A possible
      approach to patients with carcinomatosis from gastric cancer includes the use of
      neoadjuvant bidirectional chemotherapy (intraperitoneal and intravenous or NIPS)
      with subsequent cytoreduction and HIPEC for patients with a positive response to
      NIPS. Even more importantly, in several randomized studies and one meta-analysis,
      the use of intraperitoneal chemotherapy was beneficial in patients undergoing
      surgery for a primary, advanced gastric cancer. CONCLUSION: It appears that a
      significant amount of data has accumulated regarding the KEY optimal use of
      cytoreductive surgery and intraperitoneal chemotherapy in gastric cancer. An
      algorithm for the management of gastric cancer patients incorporating these
      treatment modalities can be implemented.

PMID- 22595735
TI  - Laparoscopic colectomy is a reliable option for colon cancer treatment.
AB  - AIMS: To report oncological results in a remarkable single institution series of
      laparoscopic colectomy for cancer. METHODS: 340 not selected patients with
      adenocarcinoma of colon underwent laparoscopic colonic resection in a five years
      period (2004-2008). Of the 340 patients, there were 185 male and 155 female. The
      mean age was 68 years (31-92). Of the 340 procedures, 175 were laparoscopic right
      colectomy and 165 laparoscopic left colectomy. No tumor touch technique, ligation
      at vascular origin, adequate lymphadenectomy and minilaparotomy protection
      against cells implant was the main landmarks of all cases. RESULTS: There was no
      intraoperative mortality. Twenty patients (5.8%) were converted to open surgery.
      Two patients (0,58%) died in the postoperative period. Five major complications
      occurred (1,5%) in the postoperative period. The average hospital stay for
      patients who underwent right colectomy was 6.7 days (4-27) and 6.9 for patients
      underwent left hemicolectomy (4-23). The average number of lymph nodes removed
      was 15.6. In a mean 38 months follow-up (25-78) there were 16 incisional hernias,
      12 after right colectomy and 4 after left. Eight patients (4,5%) who underwent
      laparoscopic right colectomy and ten (6%) of the left colectomy group developed a
      metastatic disease. The overall mortality rate was 10.8%; 14.3% for patients who
      underwent resection of the right colon and 7.2% for the left colectomy series.
      CONCLUSIONS: Laparoscopic colectomy for cancer is feasible, safe and not
      encumbered by an higher complications rate compared to open colectomy. If the
      oncological criteria are respected, the results are at least noniferior to the
      open access.

PMID- 22595736
TI  - An unexpected surprise at the end of a "quiet" cholecystectomy. A case report and
      review of the literature.
AB  - BACKGROUND: Anatomic unexpected variations in biliary tree may be discovered
      during laparoscopic cholecystectomy. CASE REPORT: A 57-year-old man was admitted
      for abdominal pain, vomiting and mild jaundice. Abdominal ultrasonography
      revealed a gallbladder containing multiple stones and biliary sludge. All pre
      operative investigations showed no anatomical variations in extrahepatic biliary
      tree. During surgical intervention an accessory extrahepatic duct, connecting the
      IV segment of the liver to the fundus of gallbladder, was discovered.
      CONCLUSIONS: Pre-operative routine investigations for gall stones diseases may
      not reveal anatomic variations of biliary tree.

PMID- 22595737
TI  - Personal technique for treatment of perianal fistulas in outpatients.
AB  - AIM: Presentation of a personal technique for the treatment of perineal fistulas
      in outpatients. MATERIAL OF STUDY: 17 patients with complete non-complex linear
      intersphincteric or trans-sphincteric fistulas were treated with this technique.
      First we facilitated the cannulation, then we used the same catheters to place
      the "seton". We had to use a more subtle and smooth, rugged nylon thread, instead
      of the floss, due to the difference between the large size of the silk thread and
      the small lumen of the cannula. RESULTS: The elastic traction has determined not
      only a valid mean of capillary drainage, but also a rapid passage through the
      tissues without any functional impairment, in times ranging from 2 to 4 weeks.
      DISCUSSION: The traditional surgery is burdened by a significant number of
      relapses . This is due to the anatomical characteristics of the anal canal, to
      the difficulty to ensure the integrity of the sphincteric structures and to the
      position of the fistula. It's essential to identify the whole extension of the
      fistula to avoid it's partial removal and the persistence of granulation tissue
      therefore. With our technique, we got a good drainage of the fistula, avoiding to
      leave any residues or to create false paths causing relapses as may happen with
      the explorers. CONCLUSIONS: The discomfort suffered by patients was minimal and
      the results achieved led us to support a greater diffusion of this technique in
      outpatients.

PMID- 22595738
TI  - [Experimental teaching program on cooperation between "Sapienza" University of
      Rome and the University Hospital "Le Bon Samaritain" in N'Djamena, Chad].
AB  - BACKGROUND: The shortage of essential surgical care in sub-Saharan Africa is a
      worldwide problem. Lack of healthcare workers, surgeons and very limited
      resources are the reason for this critical health crisis. Furthermore in Africa
      many physicians as soon as they get a degree emigrate in more attractive
      countries. METHODS: "Multidisciplinary teaching support to a new Faculty of
      Medicine in N'Djamena - Chad" is a teaching cooperation program between
      "Sapienza" University of Rome and the University Hospital "Le Bon Samaritain" in
      N'Djamena, Chad. The project started in 2010, with the aim of cooperating in
      teaching medical students of African origin and in training Italian residents in
      sub-Saharan surgical and internal pathologies. In Chad the greatest surgical
      burden (about 11% of the total global diseases) is created by injuries, cancers,
      congenital anomalies, appendicitis, bowel obstructions, hernias, abscesses (by
      amebiasis or others) and obstetric emergencies. CONCLUSIONS: Up till now
      healthcare in Africa especially in rural areas has been provided by international
      organisations,we believe that academic collaborations between high-income and low
      income Nations is necessary to meet the real needs of the african surgical
      workforce; at the same time it is very useful for store of knowledge of our
      residents.

PMID- 22595739
TI  - Prognostic value of TP/PD-ECGF and thrombocytosis in gastric carcinoma.
AB  - AIM: Thymidine phosphorylase/platelet-derived endothelial cell growth factor
      (TP/PD-ECGF) is upregulated in several cancers and plays an important role in
      angiogenesis and invasion of solid tumors. In this study, we investigated the
      expression of TP/PD-ECGF in gastric carcinoma and its correlation with
      clinicopathological features and thrombocytosis, and also determined their
      prognostic significance. METHODS: Ninety-eight tissue specimens were resected
      from patients with gastric carcinoma. The immunohistochemical staining was used
      for expression of TP/PD-ECGF, platelet counts (PLT) of all patients before
      surgery were recorded. Patients were divided into high and low TP/PD-ECGF
      expression groups. Correlations among TP/PD-ECGF expression, PLT and the
      clinicopathological features of the patients and their prognostic values were
      studied statistically. RESULTS: Sixty-one cases of high TP/PD-ECGF expression
      (62%) and 37 cases of low TP/PD-ECGF expression (38%) were detected. There were
      21 patients with thrombocytosis (21%). The results show that high TP/PD-ECGF
      expression was correlated positively with thrombocytosis (P = 0.046, r = 0.20).
      The 5-year overall survival rate was 46.0% in patients with low TP/PD-ECGF
      expression, whereas it was only 14.8% in patients with high TP/PD-ECGF expression
      (P = 0.000). The 5-year survival rate for patients with and without
      thrombocytosis were 9.5% and 31.2%, respectively, and there was a significant
      difference between them (P = 0.0001). The multivariate Cox regression analysis
      showed that high TP/PD-ECGF expression and thrombocytosis would play a role as
      independent prognostic factors in patients with gastric carcinoma. CONCLUSIONS:
      High TP/PD-ECGF expression and thrombocytosis can be regarded as valuable tools
      for predicting overall survival in patients with gastric carcinoma.

PMID- 22595740
TI  - Effects of thread features in osseo-integrated titanium implants using a
      statistics-based finite element method.
AB  - OBJECTIVE: To investigate the influence of implant design factors in terms of
      bone integrity and implant stability. MATERIALS AND METHODS: A 3D parametric CAD
      model was developed. Then, once domain settings and boundary conditions were
      defined, a 3D FEM model was created. To simulate the physical interaction at the
      bone-implant interface, identity pairs were introduced. After generating
      different design scenarios with a DOE approach, the most significant design
      factors were obtained. RESULTS: This study showed that the geometry of the screw
      thread highly influenced the implant stability. In particular the degree of bone
      damage became minimal when adopting 0.40 mm for the thread width and 0.05 mm for
      the thickness. SIGNIFICANCE: Thread width and thickness play a crucial role to
      reduce induced stresses and damage in bone. Considering these preliminary
      results, future improvements should focus on investigating also two-factor and
      higher interactions to better understand the implant loading mechanism.

PMID- 22595741
TI  - Effects of cement thickness and bonding on the failure loads of CAD/CAM ceramic
      crowns: multi-physics FEA modeling and monotonic testing.
AB  - OBJECTIVE: To determine the influence of cement thickness and ceramic/cement
      bonding on stresses and failure of CAD/CAM crowns, using both multi-physics
      finite element analysis and monotonic testing. METHODS: Axially symmetric FEA
      models were created for stress analysis of a stylized monolithic crown having
      resin cement thicknesses from 50 to 500 MUm under occlusal loading. Ceramic
      cement interface was modeled as bonded or not-bonded (cement-dentin as bonded).
      Cement polymerization shrinkage was simulated as a thermal contraction. Loads
      necessary to reach stresses for radial cracking from the intaglio surface were
      calculated by FEA. Experimentally, feldspathic CAD/CAM crowns based on the FEA
      model were machined having different occlusal cementation spaces, etched and
      cemented to dentin analogs. Non-bonding of etched ceramic was achieved using a
      thin layer of poly(dimethylsiloxane). Crowns were loaded to failure at 5 N/s,
      with radial cracks detected acoustically. RESULTS: Failure loads depended on the
      bonding condition and the cement thickness for both FEA and physical testing.
      Average fracture loads for bonded crowns were: 673.5 N at 50 MUm cement and
      300.6N at 500 MUm. FEA stresses due to polymerization shrinkage increased with
      the cement thickness overwhelming the protective effect of bonding, as was also
      seen experimentally. At 50 MUm cement thickness, bonded crowns withstood at least
      twice the load before failure than non-bonded crowns. SIGNIFICANCE: Occlusal
      "fit" can have structural implications for CAD/CAM crowns; pre-cementation spaces
      around 50-100 MUm being recommended from this study. Bonding benefits were lost
      at thickness approaching 450-500 MUm due to polymerization shrinkage stresses.

PMID- 22595742
TI  - Postprandial dyslipidaemia and diabetes:  mechanistic and therapeutic aspects.
AB  - PURPOSE OF REVIEW: There has been a resurgence of interest in the role of
      triglyceride-rich lipoproteins in the development of atherosclerosis and
      cardiovascular disease, and this is particularly relevant to diabetes mellitus
      and the postprandial state. RECENT FINDINGS: Recent evidence suggests that
      insulin resistance in diabetes induces postprandial dyslipidemia by increasing
      the enterocytic production of chylomicrons and their remnant particles, but an
      impaired clearance capacity is also involved. Postprandial dyslipidaemia in
      diabetes induces oxidative stress, inflammation and endothelial dysfunction and
      this may be compounded by dysglycaemia. New guidelines for managing
      hypertriglyceridaemia in diabetes have been published, first-line therapies being
      improved glycaemic control, treatment of other secondary causes of dyslipidaemia
      and statin therapy, followed by judicious use of fibrates, n-3 fatty acids or
      niacin. A new role for incretin-based therapies in regulating dyslipidaemia has
      been identified. SUMMARY: Postprandial dyslipidaemia is a pivotal mechanism
      whereby diabetes can induce and accelerate atherosclerosis. Regulating the plasma
      concentrations of triglyceride-rich lipoproteins may decrease the cardiovascular
      complications of diabetes. The mechanisms of action of incretin-based treatments
      on dyslipidaemia and endothelial dysfunction need further investigation. The
      efficacy of new therapies targeted at postprandial dysmetabolism in diabetes need
      to be confirmed, against best current levels of care, in clinical endpoint
      trials.

PMID- 22595743
TI  - Male and female faces are only perceived categorically when linked to familiar
      identities--and when in doubt, he is a male.
AB  - Categorical perception (CP) is a fundamental cognitive process that enables us to
      sort similar objects in the world into meaningful categories with clear
      boundaries between them. CP has been found for high-level stimuli like human
      faces, more precisely, for the perception of face identity, expression and
      ethnicity. For sex however, which represents another important and biologically
      relevant dimension of human faces, results have been equivocal so far. Here, we
      reinvestigate CP for sex using newly created face stimuli to control two factors
      that to our opinion might have influenced the results in earlier studies. Our new
      stimuli are (a) derived from single face identities, so that changes of sex are
      not confounded with changes of identity information, and (b) "normalized" in
      their degree of maleness and femaleness, to counteract natural variations of
      perceived masculinity and femininity of faces that might obstruct evidence of
      categorical perception. Despite careful normalization, we did not find evidence
      of CP for sex using classical test procedures, unless participants were
      specifically familiarized with the face identities before testing. These results
      support the single-route hypothesis, stating that sex and identity information in
      faces are not processed in parallel, in contrast to what was suggested in the
      classical Bruce and Young model of face perception. Besides, interestingly, our
      participants show a consistent bias, before and after perceptual normalization of
      the male-female range of the test morph continua, to judge faces as male rather
      than female.

PMID- 22595744
TI  - Spatial-bisection acuity in infantile nystagmus.
AB  - This study measured spatial bisection acuity for horizontally and vertically
      separated line targets in five observers with infantile nystagmus syndrome (INS)
      and no obvious associated sensory abnormalities, and in two normal observers
      during comparable horizontal retinal image motion. For small spatial separations
      between the line targets, bisection acuity for both horizontally and vertically
      separated lines is worse in the observers with IN than normal observers. In four
      of the five observers with IN, bisection acuity for small target separations is
      poorer for horizontally compared to vertically separated lines. Because the
      motion smear generated by the retinal image motion during IN would be expected to
      influence horizontally separated targets, the degradation of bisection acuity for
      both vertical and horizontally separated lines indicates that a sensory neural
      deficit contributes to impaired visual functioning in observers with idiopathic
      IN.

PMID- 22595745
TI  - Adaptation state of the local-motion-pooling units determines the nature of the
      motion aftereffect to transparent motion.
AB  - When observers adapt to a transparent-motion stimulus, the resulting motion
      aftereffect (MAE) is typically in the direction opposite to the vector average of
      the component directions. It has been proposed that the reason for this is that
      it is the adaptation state at the local-level (i.e. of the local-motion-pooling
      units) that determines the nature of the MAE (Vidnyanszky et al. Trends in
      Cognitive Sciences, 6(4), 157-161). The adapting stimuli used in these
      experiments typically consisted of random-dot kinematograms, with each dot being
      able to move over the entire viewing aperture. Here we used spatially-localised
      global-plaid stimuli which enabled us, over the course of adaptation, to present
      either one of both motion directions at each local region. A unidirectional MAE
      was perceived when two motion directions were presented at each location and a
      transparent MAE was perceived when a single direction was presented. These
      results support the notion that it is the adaptation state at the local-motion
      pooling level that determines the nature of the MAE to transparent motion
      stimuli.

PMID- 22595746
TI  - Quantified outcome for patients with bladder exstrophy.
AB  - AIM: Outcomes of bladder exstrophy patients were studied in numerical terms using
      scoring systems for continence and health-related quality of life (HRQOL), along
      with renal function, in short-term follow up. PATIENTS AND METHODS: Patients who
      had undergone bladder-preserving exstrophy repairs, either staged or as a single
      procedure, and those who had been managed by bowel augmentation were included.
      Continence was assessed according to five variables (max. score 15) and HRQOL
      assessment was by means of a structured modified questionnaire scored on a Likert
      scale model (max. score 150). RESULTS: A total of 39 patients were followed. Mean
      age was 8.3 years and mean follow up duration 3 years. Mean HRQOL score was
      107.55 (83-133, SD +/- 19.31). Mean continence score was 8.73 (6-11, SD +/-
      1.544). CONCLUSIONS: Evaluation of bladder exstrophy outcomes should not be done
      merely by reporting the length of dry intervals. If performed in numerical terms
      as outlined in this series, patients across centres will be comparable over a
      common assessment protocol. Continence score achieved in this series was low in
      comparison to the literature due to the strict evaluation protocol.

PMID- 22595747
TI  - High prevalence of intratesticular varicocele in a post-orchidopexy cohort.
AB  - PURPOSE: Intratesticular varicocele (ITV) is an uncommon sonographic finding. A
      prevalence of up to 2% has been reported in men with testicular problems. In a
      cohort of men who had undergone prepubertal orchidopexy for acquired undescended
      testis, several cases of ITV were found. The aim of this study was to analyse the
      prevalence and clinical aspects of ITV in this cohort. METHODS: In a long-term
      follow-up study of position and growth of undescended testis after prepubertal
      orchidopexy, ultrasonography was used to identify men with ITV. Data on clinical
      presentation, testicular volume, and the location, size and Doppler aspects of
      intratesticular varicocele were collected and analysed. RESULTS: Of the 105 men,
      9 were identified with ITV (8.6%). In all patients, the side of orchidopexy
      correlated with the side of the ITV, and all were left-sided. The testis with ITV
      had a smaller volume than the testis without ITV (p = 0.026). CONCLUSIONS: A
      remarkably high prevalence of ITV (8.6%) was found as well as a smaller volume of
      the testes with ITV in a cohort of men who had undergone prepubertal orchidopexy
      for acquired undescended testis.

PMID- 22595748
TI  - Re: Macedo A Jr, Rondon A, Bacelar H, Leslie B, Ottoni S, Liguori R et al. An
      alternative channel for the Mitrofanoff principle based on transverse skin flaps:
      an extraperitoneal minimal invasive approach (the RPM technique). J Pediatr Urol
      2012;8:437.

PMID- 22595749
TI  - Involvement of rat dopaminergic system of nucleus accumbens in nicotine-induced
      anxiogenic-like behaviors.
AB  - The objective of the present study was to investigate the involvement of dopamine
      D1 and D2 receptors of the nucleus accumbens (NAc) shell in the anxiogenic-like
      effect of intra-central amygdala (CeA) nicotine administration. Male Wistar rats
      with cannula implants in the left CeA and the left shell of NAc were submitted to
      the elevated plus-maze (EPM). Intra-CeA injections of nicotine (1 MUg/rat)
      decreased % open arm time spent (%OAT) but not % open arm entries (%OAE) and
      locomotor activity, indicating the possibility of an anxiogenic-like response.
      Intra-NAc injection of D1 dopamine receptor antagonist, SCH23390 (0.5 MUg/rat)
      but not other doses of the antagonist (0.06, 0.125 and 0.25 MUg/rat) increased
      both %OAT and %OAE, showing an anxiolytic-like effect for the higher dose of the
      drug. Similar administration route of sulpiride (0.25, 0.5, 0.75 and 1 MUg/rat),
      a selective antagonist at dopamine D2 receptor, had no significant effect on
      OAT%, OAE% and locomotor activity. Moreover, intra-CeA injection of nicotine (1
      MUg) with intra-NAc injection of sub-threshold doses of antagonists increased
      %OAT and %OAE without significant effect on locomotor activity. These findings
      may suggest the involvement of dopamine transmission, through D1 and D2 receptors
      of NAc shell, in the anxiogenic-like effect of nicotine in the EPM task.

PMID- 22595750
TI  - Analysis of collaboration in crisis management: Swedish study report.
AB  - This report is a summary of a study 1 conducted at the Royal Swedish Academy of
      War Sciences to evaluate collaboration during crisis management. The study
      includes relevant legal and regulatory dynamics, as well as conclusions and
      recommendations. Rules and regulations of international interest are presented in
      the Appendix. References are limited to those of international interest.

PMID- 22595752
TI  - Magnetic properties of planar nanowire arrays of Co fabricated on oxidized step
      bunched silicon templates.
AB  - Planar nanowire (NW) arrays of Co grown on oxidized step-bunched Si(111)
      templates exhibit room temperature ferromagnetic behaviour for wire widths down
      to 25 nm. Temperature and thickness dependent magnetization studies on these
      polycrystalline NW arrays show that the magnetic anisotropy of the NW array is
      dominated by shape anisotropy, which keeps the magnetization in-plane with easy
      axis parallel to the wires. This shape related uniaxial anisotropy is preserved
      even at low temperatures (10 K). Thickness dependent studies reveal that the
      magnetization reversal is governed by the curling mode reversal for thick wires
      whereas thinner wires exhibit a more complex behaviour which is related to
      thermal effects and size distribution of the crystal grains that constitute the
      NWs.

PMID- 22595751
TI  - A systematic review of the association between immunogenomic markers and cancer
      related fatigue.
AB  - Fatigue, which is one of the most commonly reported symptoms in cancer, can
      negatively impact the functional status and the health-related quality of life of
      individuals. This paper systematically reviews 34 studies to determine patterns
      of associations between immunogenomic markers and levels of cancer-related
      fatigue (CRF). Findings from the longitudinal studies revealed that elevated
      fatigue symptoms especially of women with early stages of breast cancer were
      associated with high levels of neutrophil/monocyte, IL-1ra, and IL-6 during
      radiation therapy; high levels of CD4+, IL-1beta, and IL-6 with stressing
      stimuli; high levels of IL-1beta during chemotherapy; low NK cell levels after
      chemotherapy; and presence of homozygous IL-6 and TNF alleles. In the cross
      sectional studies, associations between levels of fatigue and immune/inflammatory
      markers were not consistently found, especially when covariates such as BMI,
      ethnicity, menopausal status, and educational level were controlled in the
      statistical analyses. However, a number of genomic markers were observed to be
      elevated mostly in fatigued breast cancer survivors in the cross-sectional
      studies. Gaps in knowledge and recommendations for future research are discussed.

PMID- 22595753
TI  - Does vitamin D really impact survival after lung transplantation?

PMID- 22595754
TI  - Regulation of lipid stores and metabolism by lipophagy.
AB  - Intracellular lipids are stored in lipid droplets (LDs) and metabolized by
      cytoplasmic neutral hydrolases to supply lipids for cell use. Recently, an
      alternative pathway of lipid metabolism through the lysosomal degradative pathway
      of autophagy has been described and termed lipophagy. In this form of lipid
      metabolism, LD triglycerides (TGs) and cholesterol are taken up by autophagosomes
      and delivered to lysosomes for degradation by acidic hydrolases. Free fatty acids
      generated by lipophagy from the breakdown of TGs fuel cellular rates of
      mitochondrial beta-oxidation. Lipophagy therefore functions to regulate
      intracellular lipid stores, cellular levels of free lipids such as fatty acids
      and energy homeostasis. The amount of lipid metabolized by lipophagy varies in
      response to the extracellular supply of nutrients. The ability of the cell to
      alter the amount of lipid targeted for autophagic degradation depending on
      nutritional status demonstrates that this process is selective. Intracellular
      lipids themselves regulate levels of autophagy by unclear mechanisms. Impaired
      lipophagy can lead to excessive tissue lipid accumulation such as hepatic
      steatosis, alter hypothalamic neuropeptide release to affect body mass, block
      cellular transdifferentiation and sensitize cells to death stimuli. Future
      studies will likely identify additional mechanisms by which lipophagy regulates
      cellular physiology, making this pathway a potential therapeutic target in a
      variety of diseases.

PMID- 22595755
TI  - The role of autophagy in the pathogenesis of glycogen storage disease type II
      (GSDII).
AB  - Regulated removal of proteins and organelles by autophagy-lysosome system is
      critical for muscle homeostasis. Excessive activation of autophagy-dependent
      degradation contributes to muscle atrophy and cachexia. Conversely, inhibition of
      autophagy causes accumulation of protein aggregates and abnormal organelles,
      leading to myofiber degeneration and myopathy. Defects in lysosomal function
      result in severe muscle disorders such as Pompe (glycogen storage disease type II
      (GSDII)) disease, characterized by an accumulation of autophagosomes. However,
      whether autophagy is detrimental or not in muscle function of Pompe patients is
      unclear. We studied infantile and late-onset GSDII patients and correlated
      impairment of autophagy with muscle wasting. We also monitored autophagy in
      patients who received recombinant alpha-glucosidase. Our data show that infantile
      and late-onset patients have different levels of autophagic flux, accumulation of
      p62-positive protein aggregates and expression of atrophy-related genes. Although
      the infantile patients show impaired autophagic function, the late-onset patients
      display an interesting correlation among autophagy impairment, atrophy and
      disease progression. Moreover, reactivation of autophagy in vitro contributes to
      acid alpha-glucosidase maturation in both healthy and diseased myotubes.
      Together, our data suggest that autophagy protects myofibers from disease
      progression and atrophy in late-onset patients.

PMID- 22595756
TI  - SIRT3 protects from hypoxia and staurosporine-mediated cell death by maintaining
      mitochondrial membrane potential and intracellular pH.
AB  - Mitochondrial sirtuin 3 (SIRT3) mediates cellular resistance toward various forms
      of stress. Here, we show that in mammalian cells subjected to hypoxia and
      staurosporine treatment SIRT3 prevents loss of mitochondrial membrane potential
      (DeltaPsi(mt)), intracellular acidification and reactive oxygen species
      accumulation. Our results indicate that: (i) SIRT3 inhibits mitochondrial
      permeability transition and loss of membrane potential by preventing HKII binding
      to the mitochondria, (ii) SIRT3 increases catalytic activity of the mitochondrial
      carbonic anhydrase VB, thereby preventing intracellular acidification, Bax
      activation and apoptotic cell death. In conclusion we propose that, in mammalian
      cells, SIRT3 has a central role in connecting changes in DeltaPsi(mt),
      intracellular pH and mitochondrial-regulated apoptotic pathways.

PMID- 22595757
TI  - CD147 induces UPR to inhibit apoptosis and chemosensitivity by increasing the
      transcription of Bip in hepatocellular carcinoma.
AB  - The unfolded protein response (UPR) is generally activated in solid tumors and
      results in tumor cell anti-apoptosis and drug resistance. However, tumor-specific
      UPR transducers are largely unknown. In the present study, we identified CD147, a
      cancer biomarker, as an UPR inducer in hepatocellular carcinoma (HCC). The
      expression of the major UPR target, Bip, was found to be positively associated
      with CD147 in human hepatoma tissues. By phosphorylating FAK and Src, CD147
      enhanced TFII-I tyrosine phosphorylation at Tyr248. CD147 also induced p-TFII-I
      nuclear localization and binding to the Bip promoter where endoplasmic reticulum
      (ER) stress response element 1 (ERSE1) (-82/-50) is the most efficient target of
      the three ERSEs, thus increasing transcription of Bip. Furthermore, by inducing
      UPR, CD147 inhibited HCC cell apoptosis and decreased cell Adriamycin
      chemosensitivity, thus decreasing the survival rate of hepatoma-bearing nude
      mice. Together, these results reveal pivotal roles for CD147 in modulating the
      UPR in HCC and raise the possibility that CD147 is a target that promotes HCC
      cell apoptosis and increases the sensitivity of tumors to anti-cancer drugs.
      Therefore, CD147 inhibition provides an opportunity to enhance the efficacy of
      existing agents and represents a novel target for HCC treatment.

PMID- 22595758
TI  - PIDDosome-independent tumor suppression by Caspase-2.
AB  - The PIDDosome, a multiprotein complex constituted of the 'p53-induced protein
      with a death domain (PIDD), 'receptor-interacting protein (RIP)-associated ICH
      1/CED-3 homologous protein with a death domain' (RAIDD) and pro-Caspase-2 has
      been defined as an activating platform for this apoptosis-related protease. PIDD
      has been implicated in p53-mediated cell death in response to DNA damage but also
      in DNA repair and nuclear factor kappa-light-chain enhancer (NF-kappaB)
      activation upon genotoxic stress, together with RIP-1 kinase and Nemo/IKKgamma.
      As all these cellular responses are critical for tumor suppression and
      deregulated expression of individual PIDDosome components has been noted in human
      cancer, we investigated their role in oncogenesis induced by DNA damage or
      oncogenic stress in gene-ablated mice. We observed that Pidd or Caspase-2 failed
      to suppress lymphoma formation triggered by gamma-irradiation or 3
      methylcholanthrene-driven fibrosarcoma development. In contrast, Caspase-2 showed
      tumor suppressive capacity in response to aberrant c-Myc expression, which did
      not rely on PIDD, the BH3-only protein Bid (BH3 interacting domain death agonist)
      or the death receptor ligand Trail (TNF-related apoptosis-inducing ligand), but
      associated with reduced rates of p53 loss and increased extranodal dissemination
      of tumor cells. In contrast, Pidd deficiency associated with abnormal M-phase
      progression and delayed disease onset, indicating that both proteins are
      differentially engaged upon oncogenic stress triggered by c-Myc, leading to
      opposing effects on tumor-free survival.

PMID- 22595759
TI  - The analgesic efficacy of transversus abdominis plane blocks in ileostomy
      takedowns: a retrospective analysis.
AB  - STUDY OBJECTIVE: To evaluate the analgesic efficacy of transversus abdominis
      plane (TAP) blocks in patients undergoing ileostomy reversal. DESIGN:
      Retrospective chart review. SETTING: University-affiliated hospital. SUBJECTS:
      The charts of 104 consecutive patients who underwent ileostomy reversal between
      November 1, 2008 and December 31, 2009 were reviewed. The charts of 69 patients
      were included in the study. Of these, 31 received a preoperative TAP block.
      MEASUREMENTS: Patients' opioid requirements intraoperatively, in the
      Postanesthesia Care Unit (PACU), and during the 24-hour period after discharge
      from the PACU were recorded and converted to intravenous (IV) morphine
      equivalents. Patient-reported numerical pain scores (0-10) from the PACU and from
      the 24-hour postoperative period also were recorded. Additional nonopioid means
      of perioperative analgesia were noted, as were duration of stay in the PACU and
      the hospital. MAIN RESULTS: Patients receiving TAP blocks required statistically
      significantly fewer opioids intraoperatively (P = 0.002), in the PACU (P =
      0.003), and over the 24-hour period postoperatively (P = 0.01) than did patients
      who did not receive a TAP block. Mean numerical pain scores while in the PACU and
      for 24 hours postoperatively also were significantly lower (P = 0.015 and P =
      0.019, respectively) in patients receiving a TAP block, as were numerical pain
      scores immediately on arrival at the PACU (P = 0.013). CONCLUSION: TAP blocks are
      an effective means of reducing perioperative pain in patients undergoing
      ileostomy reversal.

PMID- 22595760
TI  - Size dependent bioaccumulation and ecotoxicity of gold nanoparticles in an
      endobenthic invertebrate: the Tellinid clam Scrobicularia plana.
AB  - Gold nanoparticles (AuNPs) have important technological applications resulting in
      an increased potential for release to the environment, and a greater possibility
      of toxicological effects. The marine bivalve Scrobicularia plana was exposed to
      AuNPs of size 5, 15 and 40 nm during a 16 d laboratory exposure at 100 MUg Au L(
      1). After exposure to AuNPs forming aggregates (>700 nm), the clams accumulated
      Au in their soft tissues. Biochemical (biomarkers) and behavioral (burrowing and
      feeding) responses were investigated. Au NPs were responsible of metallothionein
      induction (5, 40 nm), increased activities of catalase (15, 40 nm) and superoxide
      dismutase (40 nm) and of glutathione S-transferase by the three sizes of AuNPs
      indicating defense against oxidative stress. Exposure to AuNPs impaired burrowing
      behavior. However, it must be underlined that these effects were observed at a
      dose much higher than expected in the environment.

PMID- 22595761
TI  - Imaging of metal bioaccumulation in hay-scented fern (Dennstaedtia punctilobula)
      rhizomes growing on contaminated soils by laser ablation ICP-MS.
AB  - Understanding Pb removal from the translocation stream is vital to engineering Pb
      hyperaccumulation in above ground organs, which would enhance the economic
      feasibility of Pb phytoextraction technologies. We investigated Cu, Pb, Sb and Zn
      distributions in Hay-scented fern (Dennstaedtia punctilobula) rhizomes on
      shooting range soils by laser ablation-inductively coupled plasma-mass
      spectrometry (LA-ICP-MS), analyzing digested rhizomes, stems, and fronds using
      ICP-MS. Nutrients Cu and Zn concentrated in fronds while toxic elements Pb and Sb
      did not, showing potential Pb and Sb sequestration in the rhizome. Frond and
      rhizome concentration of Pb was 0.17 +/- 0.10% and 0.32 +/- 0.21% of dry biomass,
      respectively. The 208Pb/13C and 121Sb/13C determined by LA-ICP-MS increased from
      inner sclerotic cortex to the epidermis, while Pb concentrated in the starchy
      cortex only in contaminated sites. These results suggest that concentration
      dependent bioaccumulation in the rhizome outer cortex removes Pb from the
      vascular transport stream.

PMID- 22595762
TI  - An integrated SOM-based multivariate approach for spatio-temporal patterns
      identification and source apportionment of pollution in complex river network.
AB  - In this study, three classification techniques (self-organizing maps,
      hierarchical cluster analysis and discriminant analysis) were applied to identify
      spatial water pollution levels, temporal water quality response delay phenomena
      (WQRDP), source pollution types (point, urban non-point, or agricultural non
      point). Two models (principal components analysis (PCA), and positive matrix
      factorization (PMF)) were used to do the further quantitative source
      apportionment studying. The 27 inflow rivers in spatial were divided into three
      pollution levels (A, high; B, medium; C, low). The primary pollution pattern in
      spatial Clusters A, B, and C were point, urban non-point and agricultural non
      point separately, in consideration of simultaneous land use types. Source
      apportionment results identified five typical factors in spatial Cluster A and
      six typical factors in spatial Cluster B and C as responsible for the data
      structure, explaining 80%-90% of the total variance of the dataset.

PMID- 22595763
TI  - Parent and halogenated polycyclic aromatic hydrocarbons in rice and implications
      for human health in China.
AB  - Rice is the staple food for approximate two thirds of the Chinese population.
      However, human exposure to parent and halogenated polycyclic aromatic
      hydrocarbons (PAHs) via rice consumption is still not clear for Chinese people so
      far. The goals of this work are to assess human exposure to PAHs and halogenated
      PAHs (HPAHs) via rice ingestion and the cancer risk for Chinese population. 16
      PAHs and eight HPAHs were determined in rice samples collected from 18 provinces
      in China. In general terms, the general population in China was exposed to higher
      levels of PAHs via rice ingestion in comparison to that via cereals for other
      countries. The cancer risk values induced by exposure to PAHs and HPAHs for male
      and female on each age group were between the priority risk level (10(-4)) and
      the acceptable risk level (10(-6)). Children faced the highest cancer risk,
      followed by adolescents and adults.

PMID- 22595764
TI  - Transformation of PBDE mixtures during sediment transport and resuspension in
      marine environments (Gulf of Lion, NW Mediterranean Sea).
AB  - Polybromodiphenyl ethers (PBDEs) in superficial sediments from the Gulf of Lion
      were studied. They were largely predominated by BDE 209 (98.7% of all PBDEs)
      indicating that the main source of these pollutants was the commercial mixture
      deca-BDE. This compound and the less brominated BDE exhibited a southwestward
      decreasing concentration gradient following the dominant marine currents and
      bottom relief, e.g. the Mud Belt, the submarine canyons and the Open Continental
      Slope. All PBDEs exhibited statistically significant correlations confirming the
      common origin. However, a progressive transformation of the dumped BDE 209 was
      identified showing a depletion paralleled by increases of the less brominated
      BDEs (from 8.6% to 22%). These less brominated compounds were accumulated at
      about 100-140 km away from the Rhone prodelta, e.g., at the end of the submarine
      canyons, evidencing that these transformation compounds can be accumulated at
      long distances from the dumping sites in the marine system.

PMID- 22595765
TI  - Effect of surface tension and coefficient of thermal expansion in 30 nm scale
      nanoimprinting with two flexible polymer molds.
AB  - We report on nanoimprinting of polymer thin films at 30 nm scale resolution using
      two types of ultraviolet (UV)-curable, flexible polymer molds: perfluoropolyether
      (PFPE) and polyurethane acrylate (PUA). It was found that the quality of
      nanopatterning at the 30 nm scale is largely determined by the combined effects
      of surface tension and the coefficient of thermal expansion of the polymer mold.
      In particular, the polar component of surface tension may play a critical role in
      clean release of the mold, as evidenced by much reduced delamination or broken
      structures for the less polarized PFPE mold when patterning a relatively
      hydrophilic PMMA film. In contrast, such problems were not notably observed with
      a relatively hydrophobic PS film for both polymer molds. In addition, the
      demolding characteristic was also influenced by the coefficient of thermal
      expansion so that no delamination or uniformity problems were observed when
      patterning a UV-curable polymer film at room temperature. These results suggest
      that a proper polymeric mold material needs to be chosen for patterning polymer
      films under different surface properties and processing conditions, providing
      insights into how a clean demolding characteristic can be obtained at 30 nm scale
      nanopatterning.

PMID- 22595766
TI  - Frailty and its prediction of disability and health care utilization: the added
      value of interviews and physical measures following a self-report questionnaire.
AB  - AIMS: To establish whether the prediction of the adverse outcomes disability and
      six indicators of health care utilization one and two years later by the three
      frailty domains (physical, psychological, social) of the Tilburg Frailty
      Indicator (TFI) is improved by adding interview and physical measures of frailty.
      MATERIALS AND METHODS: A representative sample of 245 Dutch community-dwelling
      persons aged 75 years and older (response rate 53%) participated in 2008, one
      year later in 2009 (n=179, 73%) and again two years later in 2010 (n=141, 58%).
      Frailty was assessed with the TFI, an easy to administer self-report measure.
      Disability was measured using the Groningen Activity Restriction Scale (GARS).
      Indicators of health care utilization were: visit to a general practitioner (gp),
      contacts with health care professionals (hcps), hospital admission, receiving
      personal care, receiving nursing care, and receiving informal care. RESULTS:
      After controlling for background characteristics, the TFI predicted disability
      and the indicators of health care utilization. Interviews and physical measures
      of frailty improved the prediction of disability. The Hospital Anxiety and
      Depression Scale (HADS-A) improved the prediction of contacts with hcps, but the
      interview and physical measures of frailty did not improve the predictions of the
      other indicators of health care utilization. CONCLUSIONS: Assessment by the self
      report TFI is sufficient for predicting six indicators of health care
      utilization, but for predicting disability the use of both the TFI and the Timed
      Up & Go (TUG) test is recommended. It is advisable assessing all three frailty
      domains when examining frailty and its prediction of adverse outcomes.

PMID- 22595767
TI  - Decreased plasma nesfatin-1 levels in patients with generalized anxiety disorder.
AB  - Nesfatin-1, a recently discovered satiety molecule, is localized in neurons of
      the hypothalamus and brain stem and colocalized with stress-related substances.
      However, the relation between nesfatin-1 and stressor related behaviors like
      anxiety and/or fear has not yet been investigated in human subjects. In the
      present study, our aim was to investigate whether there was a relationship
      between plasma nesfatin-1 levels and generalized anxiety disorder. The study
      group consisted of 40 patients (BMI, 22.98 +/- 0.56) with generalized anxiety
      disorder and 34 age-matched healthy male control subjects (23.05 +/- 0.4).
      Patients fully met the fourth Diagnostic and Statistical Manual of Mental
      Disorders, text revision. Blood samples for nesfatin-1 were drawn at the end of
      an overnight fasting period at least 10h. Plasma nesfatin-1 levels were measured
      and found significantly lower in anxiety disorder group than in control group
      (0.35 +/- 0.037 ng/ml vs. 0.63 +/- 0.080 ng/ml, respectively, p<0.05). Low
      nesfatin-1 levels may be related with generalized anxiety disorder.

PMID- 22595768
TI  - Rational design of a phthalocyanine-perylenediimide dyad with a long-lived charge
      separated state.
AB  - A new ZnPc-PDI dyad presenting for the first time a charge-separated state lower
      in energy than the triplet excited state of the ZnPc and PDI has been
      synthesized. The rational design implies the substitution of the ZnPc with
      phenoxy groups and the bay substitution of the PDI with sulfonyl substituents.
      The lifetime of the charge-separated state was 72 MUs.

PMID- 22595770
TI  - Prospective links between social anxiety and adolescent peer relations.
AB  - This study examines bi-directional links between social anxiety and multiple
      aspects of peer relations (peer acceptance, peer victimization, and relationship
      quality) in a longitudinal sample of 1528 adolescents assessed twice with one
      year between (754 females and 774 males; M = 14.7 years of age). Lower levels of
      peer acceptance predicted increases in social anxiety. Social anxiety predicted
      decreases in relationship support for males and increases in peer victimization
      for females. Collectively our findings suggest that peers seem to play a
      significant role for adolescent mental health and social anxiety seems to
      interfere with healthy peer relations. Importantly, developmental pathways for
      social anxiety seem to differ for adolescent females and males.

PMID- 22595769
TI  - Overexpression of bone morphogenetic protein 4 in STO fibroblast feeder cells
      represses the proliferation of mouse embryonic stem cells in vitro.
AB  - Embryonic stem cells (ESCs) can be propagated in vitro on feeder layers of mouse
      STO fibroblast cells. The STO cells secrete several cytokines that are essential
      for ESCs to maintain their undifferentiated state. In this study, we found
      significant growth inhibition of mouse ESCs (mESCs) cultured on STO cells
      infected with adenovirus containing a dominant-negative mutant form of IkappaB
      (rAd-dnIkappaB). This blockage of the NF-kappaB signal pathway in STO cells led
      to a significant decrease in [(3)H]thymidine incorporation and colony formation
      of mESCs. Expression profile of cytokines secreted from the STO cells revealed an
      increase in the bone morphogenetic protein4 (BMP4) transcript level in the STO
      cells infected with adenoviral vector encoding dominant negative IkappaB (rAd
      dnIkappaB). These results suggested that the NF-kappaB signaling pathway
      represses expression of BMP4 in STO feeder cells. Conditioned medium from the rAd
      dnIkappaB-infected STO cells also significantly reduced the colony size of mESCs.
      Addition of BMP4 prevented colony formation of mESCs cultured in the conditioned
      medium. Our finding suggested that an excess of BMP4 in the conditioned medium
      also inhibits proliferation of mESCs.

PMID- 22595771
TI  - An interpretation of the absorption and emission spectra of the gold dimer using
      modern theoretical tools.
AB  - The excited states of the gold dimer have been investigated using modern
      theoretical tools including the multiconfigurational exact molecular mean-field
      intermediate Hamiltonian Fock-space Coupled Cluster, X2Cmmf-IHFSCC, and the
      complete active space self-consistent field followed by second order perturbation
      theory, CASSCF/CASPT2. The computed optically active transitions have been
      benchmarked against the available experimental data and compared with time
      dependent density functional theory, TDDFT, results, both in the two- and four
      component schemes. We explored in great detail several spectroscopic properties
      such as bond lengths, potential energy surfaces (PES), vibrational frequencies
      and vibrational progressions of the ground and low-lying excited states. Our data
      show excellent agreement with the experimental measurements and present a
      significant improvement compared to previous ab initio calculations. They also
      permit a detailed investigation of the intriguing a <- X and A'<- X experimental
      bands that, according to our calculations, show an avoided energy level crossing.
      The location of this crossing is critical for a correct estimation of the
      vibrational progression and oscillator strengths of these two states. Moreover,
      among the exchange-correlation (xc) potentials, the SAOP gives the best
      excitation energies, followed by the hybrid B3LYP functional. Pure functionals
      like BLYP give by far the worst results. 

PMID- 22595772
TI  - Portable handheld ultrasound in austere environments: use in the Haiti disaster.
AB  - INTRODUCTION: A 7.0 magnitude earthquake struck Haiti on January 12, 2010,
      resulting in 222,000 deaths and 300,000 injuries. Three weeks after the initial
      quake, the New Mexico Disaster Medical Assistance Team (NM DMAT-1) was deployed
      to Haiti for ongoing medical relief. During this deployment, a portable handheld
      ultrasound machine was tested for usefulness in aiding with patient care
      decisions. OBJECTIVE: The utility of portable ultrasound to help with triage and
      patient management decisions in a major disaster setting was evaluated. METHODS:
      Retrospective observational non-blinded images were obtained on 51 patients
      voluntarily presenting to the Gheskio Field clinic at Port-au-Prince. Ultrasound
      was used for evaluation of undifferentiated hypotension, torso trauma, pregnancy,
      non-traumatic abdominal pain, deep venous thrombosis and pulmonary embolism, and
      dyspnea-chest pain, as well as for assisting with procedures. Scans were obtained
      using a Signos personal handheld ultrasound machine with images stored on a
      microSD card. Qualitative data were reviewed to identify whether ultrasound
      influenced management decisions, and results were categorized in terms of percent
      of scans that influenced management. RESULTS: Fifty-one ultrasound scans on 50
      patients were performed, with 35% interpreted as positive, 41% as negative, and
      24% as equivocal. The highest yields of information were for abdominal ultrasound
      and ultrasound related to pregnancy. Ultrasound influenced decisions on patient
      care in 70% of scans. Most of these decisions were reflected in the clinician's
      confidence in discharging a patient with or without non-emergent follow-up.
      CONCLUSION: The use of a handheld portable ultrasound machine was effective for
      patient management decisions in resource-poor settings, and decreased the need to
      triage selected patients to higher levels of care. Ultrasound was very useful for
      evaluation of non-traumatic abdominal pain. Dynamic capability is necessary for
      ultrasound evaluation of undifferentiated hypotension and cardiac and lung
      examinations. Ultrasound also was useful for guidance during procedural
      applications, and for aiding in the diagnosis of parasitic diseases.

PMID- 22595773
TI  - Acute fractures of the scaphoid bone: Systematic review and meta-analysis.
AB  - BACKGROUND: The scaphoid fractures account for 50%-80% of all carpal bone
      fractures in young individuals. Non-union of the fracture occurs in approximately
      5%-10% of undisplaced scaphoid fractures. Current management varies significantly
      among different places and surgeons. OBJECTIVES: The purpose of this review is to
      investigate the evidence of the effectiveness and safety of various treatments of
      acute scaphoid fractures. METHODOLOGY: Systematic review and metanalysis of all
      the randomised and quasi-randomised trials comparing different treatments of
      acute scaphoid fractures. RESULTS: Thirteen RCTs (Published 18 times) have met
      our inclusion criteria. The followings have been investigated: 1. Colles cast
      versus scaphoid cast. 2. Above elbow versus below elbow scaphoid cast. 3. Colles
      cast with the wrist in flexion versus Colles cast with the wrist in extension. 5.
      Operative versus non-operative treatment. 6. Union rate versus time to union.
      CONCLUSION: Scaphoid fracture can be treated by Colles cast for up to 12 weeks.
      The wrist should not be in flexion. There is no advantage of an above elbow cast
      over a below elbow cast. Operative treatment for scaphoid does not provide a
      higher union rate in undisplaced fractures, but may do in displaced fracture.
      Open approach seems to be superior to percutaneous fixation.

PMID- 22595774
TI  - Synthesis of imidazo[2,1-b]thiazoles linked to an unprotected carbohydrate
      moiety.
AB  - Two series of imidazo[2,1-b]thiazoles substituted on C-3 or C-5 with an
      unprotected carbohydrate moiety were synthesized. Different protective groups for
      position 3 of the carbohydrate moiety were tested (acetyl, tert
      butyldimethylsilyl (TBDMS), and p-methoxybenzyl (PMB)) and the latter turn out to
      be the best strategy to obtain the desired products. Full deprotection of the
      carbohydrate was performed successfully in only one step.

PMID- 22595775
TI  - Pathogenesis of sarcoidosis.
AB  - Sarcoidosis is a systemic granulomatous disorder of unknown origin. Recent
      research uncovered underlying immunological and genetic mechanisms, which will
      pave the way for more effective pharmaceutical studies. At present some of this
      knowledge is clinically exploited to monitor therapy and expected genetic
      progress will allow the development of prognostic genetic patterns or molecular
      signatures. Moreover, it has become obvious that several etiologic agents and
      cofactors will exist. These will be of animate and inanimate nature and their
      interplay with host mechanisms discussed in this review determines disease
      phenotypes.

PMID- 22595776
TI  - Ocular sarcoidosis.
AB  - Sarcoidosis, a chronic multisystem disease, is a common cause of ocular
      inflammation. Even though clinical features are well-established, diagnosis
      requires histological confirmation, which remains difficult in patients with
      uveitis. Thus, the frequency of ocular sarcoidosis is overestimated. A set of
      criteria has been recently established in order to improve the diagnostic
      procedure. New imaging tools will enable the ophthalmologist to evaluate the
      level of ocular inflammation and to monitor its resolution after treatment
      initiation. Indocyanine green angiography and optical coherence tomography have
      dramatically improved our understanding of choroidal granulomas and macular
      edema. Treatment is based on topical and systemic corticosteroids in most of the
      cases, but immuno-suppressive agents may be necessary. The visual outcome remains
      favorable but severe complications, including glaucoma, cystoid macular edema and
      choroidal neovascularization, may need a prompt and aggressive management.

PMID- 22595777
TI  - Neurosarcoidosis: Clinical manifestations, diagnosis and treatment.
AB  - Sarcoidosis is an idiopathic granulomatous disease affecting multiple organs.
      Neurosarcoidosis, involving the central and/or peripheral nervous systems, is a
      relatively rare form of sarcoidosis. Its clinical manifestations include cranial
      neuropathies, meningitis, neuroendocrinological dysfunction, hydrocephalus,
      seizures, neuropsychiatric symptoms, myelopathy and neuropathies. The diagnosis
      is problematic, especially when occurring as an isolated form without other organ
      involvement. Distinguishing neurosarcoidosis from other granulomatous diseases
      and multiple sclerosis is especially important. Although biopsy of neural tissue
      is the gold standard for the diagnosis of neurosarcoidosis, this is often not
      practical and the diagnosis must be inferred though other tests, often coupled
      with biopsy of extraneural organs. Corticosteroids and other immuno-suppressants
      are frequently used for the treatment of neurosarcoidosis. This article reviews
      the epidemiology, pathogenesis, pathology, clinical features, diagnosis,
      diagnostic tests, diagnostic criteria, and therapy of neurosarcoidosis.

PMID- 22595778
TI  - Current status of transrectal ultrasound techniques in prostate cancer.
AB  - PURPOSE OF REVIEW: Present the current status of transrectal ultrasound imaging
      in prostate cancer (PCa) and discuss the latest techniques now under preclinical
      evaluation. RECENT FINDINGS: Three-dimensional ultrasound and quantification
      techniques are superior to two-dimensional ultrasound in visualizing PCa and can
      be beneficial in staging prior to operation. Doppler-guided biopsies are more
      likely to yield positive results, especially when high Gleason scores are
      present. Furthermore, Vardenafil usage strengthens Doppler enhancement and can
      help in increasing the diagnostic accuracy of Doppler. Multiple studies show
      elastography to be a promising new addition to the ultrasound investigations for
      detection of PCa. Especially the recently introduced Shear Wave Elastography
      shows decreased user dependency and increased PCa detection rates. MRI can also
      aid in the diagnostics of PCa. However, MRI-guided biopsies are more complicated
      compared to ultrasound guidance. MRI/ultrasound fusion combines best of both
      techniques and, although just recently emerged, the studies available show
      promising PCa detection rates. SUMMARY: Technical improvements in classical
      ultrasound modalities (2D/3D-greyscale, Doppler) and new modalities
      (elastography/MRI/ultrasound fusion) raised the accuracy of PCa detection.
      Especially latest elastography and MRI/ultrasound fusion are showing promising
      results in PCa visualization.

PMID- 22595779
TI  - Vaginal mesh update:  a look at the issues.

PMID- 22595780
TI  - Composite material made of plasmonic nanoshells with quantum dot cores: loss
      compensation and epsilon-near-zero physical properties.
AB  - A theoretical investigation of loss-compensation capabilities in composite
      materials made of plasmonic nanoshells is carried out by considering quantum dots
      (QDs) as the nanoshells' cores. The QD and metal permittivities are modeled
      according to published experimental data. We determine the modes with real or
      complex wavenumber able to propagate in a 3D periodic lattice of nanoshells. Mode
      analysis is also used to assess that only one propagating mode is dominant in the
      composite material whose optical properties can hence be described via
      homogenization theory. Therefore, the material effective permittivity is found by
      comparing different techniques: (i) the mentioned mode analysis, (ii) Maxwell
      Garnett mixing rule and (iii) the Nicolson-Ross-Weir method based on transmission
      and reflection when considering a metamaterial of finite thickness. The three
      methods are in excellent agreement, because the nanoshells considered in this
      paper are very subwavelength, thus justifying the parameter homogenization. We
      show that QDs are able to provide loss-compensated epsilon-near-zero
      metamaterials and also loss-compensated metamaterials with large negative values
      of permittivity. Besides compensating for losses, the strong gain via QD can
      provide optical amplification with particular choices of the nanoshell and
      lattice dimensions.

PMID- 22595784
TI  - Regulation of neuronal GABA(B) receptor functions by subunit composition.
AB  - GABA(B) receptors (GABA(B)Rs) are G protein-coupled receptors for GABA, the main
      inhibitory neurotransmitter in the CNS. In the past 5 years, notable advances
      have been made in our understanding of the molecular composition of these
      receptors. GABA(B)Rs are now known to comprise principal and auxiliary subunits
      that influence receptor properties in distinct ways. The principal subunits
      regulate the surface expression and the axonal versus dendritic distribution of
      these receptors, whereas the auxiliary subunits determine agonist potency and the
      kinetics of the receptor response. This Review summarizes current knowledge on
      how the subunit composition of GABA(B)Rs affects the distribution of these
      receptors, neuronal processes and higher brain functions.

PMID- 22595785
TI  - Apoptotic and non-apoptotic roles of caspases in neuronal physiology and
      pathophysiology.
AB  - Caspases are cysteine proteases that mediate apoptosis, which is a form of
      regulated cell death that effectively and efficiently removes extra and
      unnecessary cells during development. In the mature nervous system, caspases are
      not only involved in mediating cell death but also regulatory events that are
      important for neural functions, such as axon pruning and synapse elimination,
      which are necessary to refine mature neuronal circuits. Furthermore, caspases can
      be reactivated to cause cell death as well as non-lethal changes in neurons
      during numerous pathological processes. Thus, although a global activation of
      caspases leads to apoptosis, restricted and localized activation may control
      normal physiology and pathophysiology in living neurons. This Review explores the
      multiple roles of caspase activity in neurons.

PMID- 22595788
TI  - Peptide production and decay rates affect the quantitative accuracy of protein
      cleavage isotope dilution mass spectrometry (PC-IDMS).
AB  - No consensus has been reached on the proper time to add stable-isotope labeled
      (SIL) peptides in protein cleavage isotope dilution mass spectrometry workflows.
      While quantifying 24 monolignol pathway enzymes in the xylem tissue of Populus
      trichocarpa, we compared the protein concentrations obtained when adding the SIL
      standard peptides concurrently with the enzyme or after quenching of the
      digestion (i.e. postdigestion) and observed discrepancies for nearly all tryptic
      peptides investigated. In some cases, greater than 30-fold differences were
      observed. To explain these differences and potentially correct for them, we
      developed a mathematical model based on pseudo-first-order kinetics to account
      for the dynamic production and decay (e.g. degradation and precipitation) of the
      native peptide targets in conjunction with the decay of the SIL peptide
      standards. A time course study of the digests confirmed the results predicted by
      the proposed model and revealed that the discrepancy between concurrent and
      postdigestion introduction of the SIL standards was related to differential decay
      experienced by the SIL peptide and the native peptide in each method. Given these
      results, we propose concurrent introduction of the SIL peptide is most
      appropriate, though not free from bias. Mathematical modeling of this method
      reveals that overestimation of protein quantities would still result when rapid
      peptide decay occurs and that this bias would be further exaggerated by slow
      proteolysis. We derive a simple equation to estimate the bias for each peptide
      based on the relative rates of production and decay. According to this equation,
      nearly half of the peptides evaluated here were estimated to have quantitative
      errors greater than 10% and in a few cases over 100%. We conclude that the
      instability of peptides can often significantly bias the protein quantities
      measured in protein cleavage isotope dilution mass spectrometry-based assays and
      suggest peptide stability be made a priority when selecting peptides to use for
      quantification.

PMID- 22595786
TI  - The origin of extracellular fields and currents--EEG, ECoG, LFP and spikes.
AB  - Neuronal activity in the brain gives rise to transmembrane currents that can be
      measured in the extracellular medium. Although the major contributor of the
      extracellular signal is the synaptic transmembrane current, other sources-
      including Na(+) and Ca(2+) spikes, ionic fluxes through voltage- and ligand-gated
      channels, and intrinsic membrane oscillations--can substantially shape the
      extracellular field. High-density recordings of field activity in animals and
      subdural grid recordings in humans, combined with recently developed data
      processing tools and computational modelling, can provide insight into the
      cooperative behaviour of neurons, their average synaptic input and their spiking
      output, and can increase our understanding of how these processes contribute to
      the extracellular signal.

PMID- 22595787
TI  - Insights into CNS ageing from animal models of senescence.
AB  - In recent years, novel model systems have made significant contributions to our
      understanding of the processes that control the ageing of whole organisms.
      However, there are limited data to show that the mechanisms that gerontologists
      have identified as having a role in organismal ageing contribute significantly to
      the ageing of the central nervous system. Two recent discoveries illustrate this
      particularly well. The first is the consistent failure of researchers to
      demonstrate a simple relationship between organismal ageing and oxidative stress-
      a mechanism often assumed to have a primary role in brain ageing. The second is
      the demonstration that senescent cells play a causal part in organismal ageing
      but remain essentially unstudied in a CNS context. We argue that the animal
      models now available (including rodents, flies, molluscs and worms), if properly
      applied, will allow a paradigm shift in our current understanding of the normal
      processes of brain ageing.

PMID- 22595789
TI  - Peptide identification by tandem mass spectrometry with alternate fragmentation
      modes.
AB  - The high-throughput nature of proteomics mass spectrometry is enabled by a
      productive combination of data acquisition protocols and the computational tools
      used to interpret the resulting spectra. One of the key components in mainstream
      protocols is the generation of tandem mass (MS/MS) spectra by peptide
      fragmentation using collision induced dissociation, the approach currently used
      in the large majority of proteomics experiments to routinely identify hundreds to
      thousands of proteins from single mass spectrometry runs. Complementary to these,
      alternative peptide fragmentation methods such as electron capture/transfer
      dissociation and higher-energy collision dissociation have consistently achieved
      significant improvements in the identification of certain classes of peptides,
      proteins, and post-translational modifications. Recognizing these advantages,
      mass spectrometry instruments now conveniently support fine-tuned methods that
      automatically alternate between peptide fragmentation modes for either different
      types of peptides or for acquisition of multiple MS/MS spectra from each peptide.
      But although these developments have the potential to substantially improve
      peptide identification, their routine application requires corresponding
      adjustments to the software tools and procedures used for automated downstream
      processing. This review discusses the computational implications of alternative
      and alternate modes of MS/MS peptide fragmentation and addresses some practical
      aspects of using such protocols for identification of peptides and post
      translational modifications.

PMID- 22595791
TI  - Photo-induced electrochemical anodization of p-type silicon: achievement and
      demonstration of long term surface stability.
AB  - Surface stability is achieved and demonstrated by porous  silicon (PS) fabricated
      using a wavelength-dependent photo-electrochemical (PEC) anodization technique.
      During anodization, the photon flux for all wavelengths was kept constant while
      only the effect of light wavelength on the surface morphology of PS was
      investigated. PS optical sensors were realized, characterized and tested using a
      photoluminescence (PL) quenching technique. An aliphatic chain of alcohols
      (methanol to n-octanol) was detected in the range of 10-200 ppm. Long term
      surface stability was observed from samples prepared under red (750-620 nm) and
      green illumination (570-495 nm), where the PL quenching cycles evoke the
      possibility of using PS for stable sensor device applications. This study
      provides a route for preparing highly sensitive organic vapour sensors with a
      precise selection of the fabrication parameters and demonstrating their prolonged
      performance.

PMID- 22595790
TI  - Chemical punch packed in venoms makes centipedes excellent predators.
AB  - Centipedes are excellent predatory arthropods that inject venom to kill or
      immobilize their prey. Although centipedes have long been known to be venomous,
      their venoms remain largely unexplored. The chemical components responsible for
      centipede predation and the functional mechanisms are unknown. Twenty-six
      neurotoxin-like peptides belonging to ten groups were identified from the
      centipede venoms, Scolopendra subspinipes mutilans L. Koch by peptidomics
      combined with transcriptome analysis, revealing the diversity of neurotoxins.
      These neurotoxins each contain two to four intramolecular disulfide bridges, and
      in most cases the disulfide framework is different from that found in neurotoxins
      from the venoms of spiders, scorpions, marine cone snails, sea anemones, and
      snakes (5S animals). Several neurotoxins contain potential insecticidal
      abilities, and they are found to act on voltage-gated sodium, potassium, and
      calcium channels, respectively. Although these neurotoxins are functionally
      similar to the disulfide-rich neurotoxins found in the venoms of 5S animals in
      that they modulate the activity of voltage-gated ion channels, in almost all
      cases the primary structures of the centipede venom peptides are unique. This
      represents an interesting case of convergent evolution in which different
      venomous animals have evolved different molecular strategies for targeting the
      same ion channels in prey and predators. Moreover, the high level of biochemical
      diversity revealed in this study suggests that centipede venoms might be
      attractive subjects for prospecting and screening for peptide candidates with
      potential pharmaceutical or agrochemical applications.

PMID- 22595792
TI  - Inhibition of tumor angiogenesis and growth by nanoparticle-mediated p53 gene
      therapy in mice.
AB  - Mutation of the p53 tumor suppressor gene, the most common genetic alteration in
      human cancers, results in more aggressive disease and increased resistance to
      conventional therapies. Aggressiveness may be related to the increased angiogenic
      activity of cancer cells containing mutant p53. To restore wild-type p53 function
      in cancer cells, we developed polymeric nanoparticles (NPs) for p53 gene
      delivery. Previous in vitro and in vivo studies demonstrated the ability of these
      NPs to provide sustained intracellular release of DNA, thus sustained gene
      transfection and decreased tumor cell proliferation. We investigated in vivo
      mechanisms involved in NP-mediated p53 tumor inhibition, with focus on
      angiogenesis. We hypothesize that sustained p53 gene delivery will help decrease
      tumor angiogenic activity and thus reduce tumor growth and improve animal
      survival. Xenografts of p53 mutant tumors were treated with a single intratumoral
      injection of p53 gene-loaded NPs (p53NPs). We observed intratumoral p53 gene
      expression corresponding to tumor growth inhibition, over 5 weeks. Treated tumors
      showed upregulation of thrombospondin-1, a potent antiangiogenic factor, and a
      decrease in microvessel density vs controls (saline, p53 DNA alone, and control
      NPs). Greater levels of apoptosis were also observed in p53NP-treated tumors.
      Overall, this led to significantly improved survival in p53NP-treated animals. NP
      mediated p53 gene delivery slowed cancer progression and improved survival in an
      in vivo cancer model. One mechanism by which this was accomplished was disruption
      of tumor angiogenesis. We conclude that the NP-mediated sustained tumor p53 gene
      therapy can effectively be used for tumor growth inhibition.

PMID- 22595793
TI  - Expression of inhibitor of growth 4 by HSV1716 improves oncolytic potency and
      enhances efficacy.
AB  - We have isolated and characterized a novel variant of the replication-competent
      oncolytic HSV1716 that expresses inhibitor of growth 4 (Ing4) (HSV1716Ing4). We
      demonstrate that Ing4 expression enhances progeny output during HSV1716 infection
      of human tumor cells both in vitro and in vivo, thereby significantly augmenting
      its oncolytic potency. In tissue culture, compared with HSV1716, HSV1716Ing4
      produced significantly higher numbers of infectious progeny in human squamous
      cell carcinoma (SCC), breast, ovarian, prostate and colorectal cancer cell lines.
      Immediate-early expression of Ing4 was crucial for this effect and an intact Ing4
      was required as there was no enhanced progeny production with HSV1716 variants
      that expressed Ing4 mutants lacking the C-terminal plant homeodomain domain or
      conserved nuclear localization signals. In mouse xenograft models of SCC, ovarian
      and breast cancer, HSV1716Ing4 was significantly more efficacious than HSV1716
      with at least 1000-fold more infectious virus found in tumors after HSV1716Ing4
      treatment compared with tumors from HSV1716 treatment. Using a sensitive herpes
      simplex virus type 1 (HSV-1) PCR, virus DNA was only detected in tumors and was
      not detected in the DNA extracted from any organs of the injected mice
      demonstrating that, like HSV1716, HSV1716Ing4 replication is exclusively
      restricted to tumor cells. Our results suggest that the potential for enhanced
      tumor destruction by oncolytic HSV expressing Ing4 merits clinical investigation.

PMID- 22595795
TI  - Interferon-beta lipofection I. Increased efficacy of chemotherapeutic drugs on
      human tumor cells derived monolayers and spheroids.
AB  - We evaluated the effect of hIFNbeta gene transfer alone or in combination with
      different antineoplastic drugs commonly used in cancer treatment. Five human
      tumor-derived cell lines were cultured as monolayers and spheroids. Four cell
      lines (Ewing sarcomas EW7 and COH, melanoma M8 and mammary carcinoma MCF-7) were
      sensitive to hIFNbeta gene lipofection. Although this effect appeared in both
      culture configurations, spheroids showed a relative multicellular resistance
      (insensitive colon carcinoma HT-29 excluded). EW7 and M8 hIFNbeta-expressing
      cells were exposed to different concentrations of bleomycin, bortezomib,
      carboplatin, doxorubicin, etoposide, methotrexate, paclitaxel and vincristine in
      both configuration models. In chemotherapy-sensitive EW7 monolayers, the
      combination of hIFNbeta gene and antineoplastic drugs displayed only additive or
      counteractive (methotrexate) effects, suggesting that cytotoxic mechanisms
      triggered by hIFNbeta gene lipofection could be saturating the signaling
      pathways. Conversely, in chemotherapy-resistant EW7 spheroids or M8 cells, the
      combination of hIFNbeta with drugs that mainly operate at the genotoxic level
      (doxorubicin, methotrexate and paclitaxel) presented only additive effects.
      However, drugs that also increase pro-oxidant species can complement the
      antitumor efficacy of the hIFNbeta gene and clearly caused potentiated effects
      (bleomycin, bortezomib, carboplatin, etoposide and vincristine). The great
      bystander effect induced by hIFNbeta gene lipofection could be among the main
      causes of its effectiveness, because only 1 or 2% of EW7 or M8 hIFNbeta
      expressing cells killed more than 60 or 80% of cell population, respectively.

PMID- 22595796
TI  - Differing structural characteristics of molten globule intermediate of peanut
      lectin in urea and guanidine-HCl.
AB  - The structural characteristics of exclusive equilibrium molten globule-like
      intermediate formed during peanut lectin unfolding in urea and guanidine
      hydrochloride (GdnHCl) have been investigated by size-exclusion chromatography,
      circular dichroism, fluorescence, phosphorescence, and chemical modification. The
      elution behavior and 8-anilino-1-naphthalenesulfonate binding indicate a less
      compact tertiary structure in urea than in GdnHCl. Further, the urea-induced
      intermediate reveals perturbed, nonnative typical beta-sheet conformation in
      contrast to native-like atypical beta-structure in GdnHCl. N-bromosuccinimide
      oxidation shows that none of three tryptophan residues is modified for GdnHCl
      induced intermediate while one gets oxidized in urea. Such difference in
      tryptophan environment is supported by acrylamide quenching (Stern-Volmer
      constant being 3.2 and 5.8 M(-1) respectively), and phosphorescence studies at 77
      K which show a blue-shift of (0, 0) band from 412.4 nm (GdnHCl) to 411.4 nm
      (urea). These results may provide important insight into the differential effects
      of GdnHCl and urea on the structural characteristics of intermediate state(s) in
      protein folding.

PMID- 22595794
TI  - Peptide targeting of adenoviral vectors to augment tumor gene transfer.
AB  - Adenovirus serotype 5 remains one of the most promising vectors for delivering
      genetic material to cancer cells for imaging or therapy, but optimization of
      these agents to selectively promote tumor cell infection is needed to further
      their clinical development. Peptide sequences that bind to specific cell surface
      receptors have been inserted into adenoviral capsid proteins to improve tumor
      targeting, often in the background of mutations designed to ablate normal
      ligand:receptor interactions and thereby reduce off target effects and toxicities
      in non-target tissues. Different tumor types also express highly variable
      complements of cell surface receptors, so a customized targeting strategy using a
      particular peptide in the context of specific adenoviral mutations may be needed
      to achieve optimal efficacy. To further investigate peptide targeting strategies
      in adenoviral vectors, we used a set of peptide motifs originally isolated using
      phage display technology that evince tumor specificity in vivo. To demonstrate
      their abilities as targeting motifs, we genetically incorporated these peptides
      into a surface loop of the fiber capsid protein to construct targeted adenovirus
      vectors. We then systematically evaluated the ability of these peptide targeted
      vectors to infect several tumor cell types, both in vitro and in vivo, in a
      variety of mutational backgrounds designed to reduce CAR and/or HSG-mediated
      binding. Results from this study support previous observations that peptide
      insertions in the HI loop of the fiber knob domain are generally ineffective when
      used in combination with HSG detargeting mutations. The evidence also suggests
      that this strategy can attenuate other fiber knob interactions, such as CAR
      mediated binding, and reduce overall viral infectivity. The insertion of peptides
      into fiber proved more effective for targeting tumor cell types expressing low
      levels of CAR receptor, as this strategy can partially compensate for the very
      low infectivity of wild-type adenovirus in those cells. Nevertheless, the
      incorporation of relatively low affinity peptide ligands into the fiber knob,
      while effective in vitro, has only minimal targeting efficacy in vivo and
      highlights the importance of high affinity ligand:receptor interactions to
      achieve tumor targeting.

PMID- 22595797
TI  - Evolution of US military humanitarian assistance.

PMID- 22595798
TI  - Pazopanib and the treatment palette for soft-tissue sarcoma.

PMID- 22595800
TI  - Thomas Wakley (1795-1862): a biographical sketch.
AB  - Thomas Wakley--founding editor of The Lancet, member of Parliament, coroner and,
      for 12 years, all three simultaneously--died 150 years ago. His fullest biography
      is more than a century old, but still provides a good account of the struggles
      and achievements of this extraordinary yet at times rather difficult and
      overstretched man. Nonetheless, there are gaps, and this anniversary provides a
      chance to fill in a few of them.

PMID- 22595801
TI  - Sudden unexpected death in children with epilepsy: the many faces of fungal
      pathogenicity.
AB  - Epilepsy is one of the most prevalent neurological diseases worldwide. The
      mortality rates are considerably higher in people with epilepsy than would be
      expected in a healthy population and sudden unexpected death in epilepsy (SUDEP)
      is the most frequent epilepsy-related category of death. Most children had
      seizures before the occurrence of the fatal event and autonomic dysfunction has
      been proposed as mechanisms of sudden death in this population. Is this sense, we
      raise the question whether is there a possible relationship between SUDEP in
      children and fungal pathogenicity. Indeed, the role of fungal pathogenicity in
      the establishment of epilepsy and even in cases of SUDEP has an interesting role
      in this scenario. Moreover, maternal infections during pregnancy have been
      associated with an increased risk for several brain disorders, however, this fact
      is still considered uncertain with respect to epilepsy. Based on this information
      and considering that maternal-fetal yeast infection is directly associated with
      an increased risk for epilepsy in childhood and that some patients have medically
      intractable epilepsy, the chances of these children suffering a fatal event
      cannot be overlooked by healthcare professionals. Thus, as exact knowledge
      regarding this association is lacking, some possibilities could be evaluated, and
      more emphasis on translational research would contribute to further progress to
      the knowledge of SUDEP.

PMID- 22595799
TI  - Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double
      blind, placebo-controlled phase 3 trial.
AB  - BACKGROUND: Pazopanib, a multitargeted tyrosine kinase inhibitor, has single
      agent activity in patients with advanced non-adipocytic soft-tissue sarcoma. We
      investigated the effect of pazopanib on progression-free survival in patients
      with metastatic non-adipocytic soft-tissue sarcoma after failure of standard
      chemotherapy. METHODS: This phase 3 study was done in 72 institutions, across 13
      countries. Patients with angiogenesis inhibitor-naive, metastatic soft-tissue
      sarcoma, progressing despite previous standard chemotherapy, were randomly
      assigned by an interactive voice randomisation system in a 2:1 ratio in permuted
      blocks (with block sizes of six) to receive either pazopanib 800 mg once daily or
      placebo, with no subsequent cross-over. Patients, investigators who gave the
      treatment, those assessing outcomes, and those who did the analysis were masked
      to the allocation. The primary endpoint was progression-free survival. Efficacy
      analysis was by intention to treat. The trial is registered with
      ClinicalTrials.gov, number NCT00753688. FINDINGS: 372 patients were registered
      and 369 were randomly assigned to receive pazopanib (n=246) or placebo (n=123).
      Median progression-free survival was 4.6 months (95% CI 3.7-4.8) for pazopanib
      compared with 1.6 months (0.9-1.8) for placebo (hazard ratio [HR] 0.31, 95% CI
      0.24-0.40; p<0.0001). Overall survival was 12.5 months (10.6-14.8) with pazopanib
      versus 10.7 months (8.7-12.8) with placebo (HR 0.86, 0.67-1.11; p=0.25). The most
      common adverse events were fatigue (60 in the placebo group [49%] vs 155 in the
      pazopanib group [65%]), diarrhoea (20 [16%] vs 138 [58%]), nausea (34 [28%] vs
      129 [54%]), weight loss (25 [20%] vs 115 [48%]), and hypertension (8 [7%] vs 99
      [41%]). The median relative dose intensity was 100% for placebo and 96% for
      pazopanib. INTERPRETATION: Pazopanib is a new treatment option for patients with
      metastatic non-adipocytic soft-tissue sarcoma after previous chemotherapy.
      FUNDING: GlaxoSmithKline.

PMID- 22595802
TI  - On the role of pentoxifylline versus other TNF-alpha inhibitors in the prevention
      of hepatorenal syndrome.

PMID- 22595803
TI  - Inducing pluripotency using in vivo gene therapy.
AB  - Since the original study of Takahashi and Yamanaka in 2006 [1], the field of
      induced pluripotent stem (iPS) cells has made a great progress. Since then, a
      number of different cell types have been successfully brought to a state of
      pluripotency and a different set of transcription factors have been reported to
      be sufficient to reprogram mouse and human somatic cells. Although still with low
      efficiency of reprogramming, the patient- and disease-specific therapy represents
      the most valuable outcome of the whole area of iPS cells. Herein we hypothesize
      that inducing pluripotency in vivo might be an interesting alternative to the
      standard ex vivo methods. In vivo reprogramming would benefit from the direct
      administration of the DNA encoding the reprogramming factors into the target
      tissue/organ of an individual. The target cells that are to be reprogrammed would
      be transduced in their natural environment that can provide all the necessary
      molecular and spatial factors that could be missing during ex vivo reprogramming.
      However, since no available data exist on in vivo induced pluripotency, it is
      difficult to predict if testing the hypothesis will provide any promising
      results. On the way to this point, a number of pilot experiments have to be
      performed to overcome many limitations and pitfalls that are arising from such a
      risky concept. Safety issues, such as the risk of somatic tumor formation, will
      likely be the crucial point to focus on during the process of proving the
      validity of the hypothesis. However, initial data from the study on inflammatory
      bowel disease suggest that there might be some beneficial effect of in vivo gene
      therapy based on reprogramming the target cells.

PMID- 22595804
TI  - A postulated role of p130 in telomere maintenance by human papillomavirus
      oncoprotein E7.
AB  - High-risk human papillomaviruses (HR-HPVs) infections is highly associated with
      the development of cervical cancer. It is now recognized that telomere length
      maintenance or extension is indispensable for carcinogenesis. The early
      oncoproteins E6 and E7 are the main malignant transformation factors of HR-HPVs
      and they maintain telomeres by different mechanisms, of which E6 protein
      activating telomerase is well documented. Reports showed that E7 protein utilized
      an alternative lengthen of telomere (ALT) mechanism to restore telomere length,
      yet the underlying molecular basis remains largely unknown. We propose that
      degradation of tumor suppressor pRb family member p130 plays an essential role in
      E7-regulated telomere extension by ALT. ALT is a mechanism based on homologous
      recombination (HR) between telomere sister chromatids, and a number of proteins
      involved in the HR pathway, such as MRN [MRE11 (meiotic recombination 11)-Rad50
      NBS1 (Nijmegen breakage syndrome 1)] complex are required for the ALT pathway. Rb
      family member p130 could inhibit ALT by interacting with Rad50, while HPV E7
      could activate ALT by degrading p130. We will make E7 mutants which are defective
      in p130 degradation to test whether these cells have a limited life span.
      Besides, immunofluorescence assay will show an ALT-related promyelocytic leukemia
      (PML) body (APBs) in E7-expressing cells. Although cervical cancer usually has
      high telomerase activities since the expressing of HPV E6, the anti-telomerase
      therapy will be unavailable for cervical cancer since it may activate E7-induced
      ALT. Our hypothesis not only enrich the knowledge of the regulation of ALT, but
      also indicate that p130 may serve as a potential suppressor of ALT, and gene
      therapy of p130 may be used in cervical cancers.

PMID- 22595805
TI  - Appropriateness for electroconvulsive therapy (ECT) can be assessed on a three
      item scale.
AB  - Electroconvulsive therapy (ECT) is the most effective and rapid treatment for
      severe depression; however, it should be prescribed to the limited number of
      patients with severe mood and psychotic disorders for whom it is clearly
      appropriate. We present an assessment scale that we hypothesize can be used to
      predict a patient's appropriateness for ECT, based on the severity, heritability,
      and episodic nature of their depression. This scale is offered as a tool to help
      the practitioner and patient gain a sense of how well the patient fits the
      profile of someone for whom ECT is a reasonable treatment option.

PMID- 22595806
TI  - S1P1 and S1P3 are potential markers of cardiac microangiopathy in diabetes.
AB  - The prevalence of diabetes is rising rapidly throughout the world, accompanying
      with the increased occurrence of cardiovascular diseases in clinic. For now, the
      diagnosis of diabetic cardiovascular diseases has mainly based on the measurement
      of glucose levels in blood and cardiac function via electrocardiogram and
      ultrasound cardiogram. However, growing evidence strongly suggests that the
      assessment of Sphingosine-1-phosphate receptor 1/3 (S1P1/3) own advantages over
      present measurements in predicting the risk of developing diabetic cardiovascular
      diseases. This hypothesis may provide concept foundation for improving early
      diagnosis of cardiac microangiopathy in diabetes.

PMID- 22595807
TI  - Atrial natriuretic peptide: a possible mediator involved in dexamethasone's
      inhibition of cell proliferation in multiple myeloma.
AB  - Atrial natriuretic peptide (ANP) has been recognized for several decades for its
      role of regulating blood pressure. Recently, cumulating evidences show that ANP
      plays an anticancer role in various solid tumors via blocking the kinase cascade
      of Ras-MEK1/2-ERK1/2 with the result of inhibition of DNA synthesis. ANP, as well
      as its receptors (NPR-A and NPR-C) has been identified present in the embryonic
      stem cell and a wide range of cancer cells. Various lymphoid organs, such as
      lymph nodes, have been detected the presence of ANP. Multiple myeloma (MM),
      though the therapies have evolved significantly, is still an incurable disease as
      B lymphocyte cell neoplasm. Dexamethasone is the cornerstone in treatment of MM
      via inactivation of Ras-MEK1/2-ERK1/2 cascade reaction. Coincidently,
      dexamethasone can increase the expression of ANP markedly. Nevertheless, the role
      of ANP in MM is unclear. Based on these results above, we raise the hypothesis
      that ANP is involved in mediating dexamethasone's inhibition of proliferation in
      MM cells, which suggests that ANP may be a potential agent to treat MM.

PMID- 22595808
TI  - Slit-Robo: a potential way to treat periodontitis.
AB  - Slit is a secreted protein known to function through the Roundabout (Robo)
      receptor. Slit has recently been shown to be an endogenously available inhibitor
      of leukocyte chemotaxis and as a chemoattractant to recruit vascular endothelial
      cells to sites for angiogenesis both in vivo and in vitro. The initiation and
      progression of periodontal diseases, is the result of complex interactions
      between the colonizing bacteria in the periodontal pockets and host immune and
      inflammatory responses. Antibiotics such as tetracyclines are commonly used in
      the management of periodontal infections and yet, have shown modest success in
      reducing neutrophil-mediated injury. Angiogenesis is important for the
      maintenance of homeostatus of periodontal tissues. However, few studies have been
      reported about angiogenesis targeted treatment for periodontitis. Based on its
      angiogenesis promoting effect and leukocyte chemotaxis inhibition effect, we
      hypothesize that Slit can be an effective immunotherapeutic agent in the
      treatment of periodontitis.

PMID- 22595809
TI  - Arrhythmias as trigger for acute exacerbations of chronic obstructive pulmonary
      disease.
AB  - PURPOSE: Acute exacerbations of chronic obstructive pulmonary disease (COPD)
      sometimes appear to occur without a precipitating cause. Heterogeneous
      repolarization and arrhythmias occur in COPD patients. Given the close inter
      relation between heart and lung, we hypothesized that unrecognized arrhythmias
      might be precipitants of acute exacerbations. METHODS: Electrocardiograms (ECG)
      of thirty patients during acute exacerbations were compared with ECG during
      stable phase. P wave dispersion was used to assess atrial depolarization
      heterogeneity, and dispersion of QT interval to assess ventricular
      repolarization. p < 0.05 was considered significant. Frequent exacerbations were
      defined as two or more exacerbations in a year. RESULTS: Mean age of patients was
      70.3 +/- 11.8 SD years. P wave dispersion was greater during acute exacerbation
      than during stable phase (56.7 +/- 19.2 vs 47.7 +/- 15.9 ms, p = 0.009). There
      was a trend toward greater QTc dispersion (108.3 +/- 61.7 vs 90.3 +/- 47.0 ms, p
      = 0.13) in acute exacerbation compared to stable phase. Sixteen (53%) had
      frequent exacerbations. There was a significant difference in PR interval during
      stable phase between those with frequent exacerbations and those without (163.9 +
      17.4 vs. 145.1 + 22.8; p = 0.02). The P wave dispersion during stable phase was
      greater in those with frequent exacerbations, but did not reach statistical
      significance (52.6 + 18.8 vs. 42.2 + 9.8 ms; p = 0.06). CONCLUSIONS: P wave
      dispersion is more in the acute phase than in stable phase, and is greater in
      patients with more frequent exacerbations. This does not prove, but suggests an
      intriguing possibility that P wave dispersion predates acute exacerbations. This
      might be a new target for prediction, prevention and therapy of acute
      exacerbations of COPD.

PMID- 22595810
TI  - Effects of home versus hospital-based exercise training in chronic heart failure.

PMID- 22595811
TI  - How to distinguish takotsubo cardiomyopathy from acute myocardial infarction
      using multimodal cardiac imaging.

PMID- 22595812
TI  - Discourse on pulse in medieval Persia--the Hidayat of Al-Akhawayni (?-983 A D.).
AB  - In a period of compilation, original observations and expansion (900-1100 A.D.),
      Persians described new clinical manifestations of the diseases and expanded the
      earlier knowledge of materia medica. In the epoch of the Arabic language
      domination in the scientific literature of this period, advent of medical authors
      to write in Farsi shined in the Persian principalities. Akhawayani Bokhari was by
      far the most outstanding scholar of the time who wrote one of the earliest
      pandects of medicine of the period, the Hidayat al-Mutallimin fi al-Tibb
      (Learner's Guide to Medicine) in new Persian. The Hidayat is a relatively short
      and simplified digest of medicine at the time providing a glimpse of high level
      of medical education at the Samanid period (819-999). The present article is a
      translation of the sections of the Hidayat related to the pulse and its
      characters and conditions affecting the pulse in an attempt to increase our
      knowledge of the medicine, and particularly the pulse examination throughout the
      medieval era.

PMID- 22595813
TI  - Enantioselective Friedel-Crafts reactions in water catalyzed by a human telomeric
      G-quadruplex DNA metalloenzyme.
AB  - A human telomeric G-quadruplex (G4DNA) metalloenzyme, assembled with G4DNA and
      Cu(2+) ions, can catalyze the enantioselective Friedel-Crafts (F-C) reaction in
      water with good enantioselectivity (up to 75% ee). Furthermore, we found that the
      absolute configuration and the enantioselectivity of the product largely depend
      on the conformation and the sequence of G4DNA.

PMID- 22595814
TI  - Current and future alternatives to warfarin for the prevention of stroke in
      atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical
      practice and is associated with a nearly 5-fold increase in the risk of stroke.
      Warfarin has been the cornerstone of treatment to reduce stroke risk in AF
      patients for decades. Although effective in preventing thrombosis, warfarin is
      difficult to manage and is associated with a 1% to 7% yearly risk of major
      hemorrhage. Until recently, there were no effective oral alternatives to
      warfarin. Dabigatran etexilate, a direct thrombin inhibitor, was approved in 2010
      for the reduction of stroke and systemic embolism in patients with nonvalvular
      AF, and the factor Xa inhibitor rivaroxaban was approved for a similar indication
      in 2011. Other late-stage orally administered agents that may be approved for
      this indication include apixaban and edoxaban; others at earlier stages of
      development will be discussed in this review as well. Nonpharmacological
      approaches to stroke prevention include left atrial appendage removal, ligation,
      or occlusion. This review examines advances in the management of stroke risk in
      AF patients, focusing on recently marketed and late-stage modalities. The advent
      of alternatives to warfarin for reducing stroke risk in AF patients may improve
      physicians' ability to offer safe and effective stroke prevention in all AF
      patients.

PMID- 22595815
TI  - A guidance pathway for the selection of novel anticoagulants in the treatment of
      atrial fibrillation.
AB  - Oral anticoagulation with vitamin K antagonists has served as the primary
      treatment for the prevention of stroke and systemic embolization in patients with
      atrial fibrillation (AF) for decades. Over the past several years, multiple novel
      oral anticoagulants targeting key mediators of coagulation, including thrombin
      and factor Xa, have been developed. Specifically, agents targeting thrombin
      (dabigatran) and factor Xa (apixaban and rivaroxaban) have either reached late
      stages of clinical development (apixaban) or have received approval (dabigatran,
      rivaroxaban) by the US Food and Drug Administration for use in patients with
      nonvalvular AF. The promising results derived from large-scale clinical trials
      with these agents compared to warfarin expand the available therapeutic options
      for the prevention of stroke and systemic embolization in this rapidly increasing
      patient population. Here we present a general guidance pathway for the initiation
      and selection of oral anticoagulants in patients with AF.

PMID- 22595816
TI  - Management of non-ST-segment elevation acute coronary syndrome: comparison of the
      updated guidelines from North America and Europe.
AB  - The American College of Cardiology/American Heart Association and the European
      Society of Cardiology published updated guidelines in 2011 for the management of
      patients with non-ST-segment elevation acute coronary syndrome. In this article,
      we highlight the most important new recommendations, review their supporting
      data, describe differences between the guidelines, and discuss new literature
      published since the latest guidelines were released. Key updates include detailed
      guidance regarding early risk stratification, use of coronary computed tomography
      angiography, selection of initial management strategy, novel antiplatelet agents,
      and new measures to enhance performance and quality. Major unique recommendations
      in the European Society of Cardiology guideline include endorsement of ticagrelor
      inhibitor or prasugrel (after delineation of coronary anatomy) as the first
      choice of P2Y12 inhibitors, establishment of protocols to identify patients for
      percutaneous coronary interventions vs. coronary artery bypass surgery, and use
      of the CRUSADE bleeding score. Meanwhile, unique recommendations in the American
      College of Cardiology/American Heart Association guideline include administration
      of prasugrel in selected patients before coronary angiography and consideration
      of continued dual antiplatelet therapy beyond 15 months after drug-eluting stent
      placement. Both guidelines include new recommendations endorsing platelet
      function and genetic testing in selected patients on clopidogrel, renal
      protection strategies, and less aggressive in patient's glycemic control. As
      these guidelines represent the most evidence-based approach, health care
      providers should become familiar with these updated recommendations to ensure
      optimal treatment of their patients with non-ST-segment elevation acute coronary
      syndrome.

PMID- 22595817
TI  - Utility of daily troponin orders for identifying acute myocardial infarction
      patients for quality improvement.
AB  - BACKGROUND: Previous studies have demonstrated low rates of adherence to American
      College of Cardiology (ACC) and American Heart Association (AHA) guidelines for
      acute myocardial infarction (AMI). Quality improvement projects increase
      compliance with recommended therapies, but identification of AMI patients is a
      major challenge. OBJECTIVE: To determine the utility of a daily troponin list in
      identifying AMI patients for a quality improvement initiative to increase
      compliance with ACC/AHA-recommended therapies. DESIGN: Quality improvement
      initiative. METHODS AND RESULTS: During a 3-month period, the charts of patients
      with elevated troponin levels were screened for a diagnosis of AMI. For those
      patients with AMI, a clinical reminder about ACC/AHA-recommended therapies was
      placed in the chart. Nearly half (46%) of our hospital population had a troponin
      level measured during their clinical course. Of these, 26% had elevated troponin
      levels and 5% had AMI. All patients with AMI were identified using the daily
      troponin list with a sensitivity of 100% and a specificity of 78.4%. The daily
      troponin list captured more AMI patients than the admitting diagnosis. Use of the
      daily troponin list and targeted clinical reminders was associated with
      maintenance of a high (>95%) compliance with recommended therapies. CONCLUSIONS:
      A daily list of inpatients with a positive troponin identified all patients with
      AMI. Targeted reminders to clinicians regarding ACC/AHA-recommended therapies for
      AMI were associated with consistent adherence to guideline-recommended therapies.

PMID- 22595818
TI  - Treatment pathways and quality improvement for patients with acute myocardial
      infarction at a tertiary care center.
AB  - The timely diagnosis and treatment of acute ST-segment elevation myocardial
      infarction (STEMI) have become paramount to improving outcomes in this
      population. Many states, including North Carolina, have established systems to
      guide regional emergency providers in caring for STEMI. We describe the current
      pathway for diagnosis and treatment of STEMI for providers referring patients to
      Duke University Hospital, including a system for expedited patient transport and
      activation of the cardiac catheterization laboratory from a wide referral base.
      There is also a structured process for review of cases and quality improvement,
      which incorporates physicians, administrators, and emergency medical personnel.

PMID- 22595819
TI  - Acute stroke initiative involving an acute care team.
AB  - The Acute Care Team Educational Initiative (ACTEI) was developed as a quality
      improvement initiative for the recognition and initial management of time
      sensitive medical conditions. For our first time-sensitive disease process, we
      focused on acute stroke [acute stroke initiative (ASI)]. As part of the larger
      ACTEI, the ASI included creating an ACT that responds to all suspected emergency
      department stroke patients. In this article, we describe the planning, process,
      and development of the ACTEI/ASI as well as how we created an acute response team
      for the diagnosis and management of suspected acute stroke.

PMID- 22595820
TI  - A novel pericardial effusion scoring index to guide decision for drainage.
AB  - BACKGROUND: Subacute pericardial tamponade can present without signs of
      cardiogenic shock. Symptoms and signs lack both sensitivity and specificity.
      METHODS: We conducted a case-control study in consecutive hospitalized patients
      with moderate-to-large pericardial effusion who had no evidence of hemodynamic
      compromise upon admission. Patients with pericardial effusion drained for
      diagnostic and/or therapeutic purposes served as cases, and patients who were not
      drained served as controls. Demographic, clinical, and laboratory data were
      obtained by retrospective chart review. Echocardiograms were reviewed by 2
      independent observers. Pericardial effusion scoring index was calculated for each
      patient based on effusion size, echocardiographic assessment of hemodynamics, and
      clinical factors. RESULTS: A total of 48 patients were included in the study:
      27(56%) patients had pericardial effusion drained and 21(44%) had clinical follow
      up without drainage. Pericardial effusion drainage was surgical in 60% of the
      cases with the mean time to drainage of 2.5 days. No significant difference was
      seen between the groups in terms of clinical hemodynamic parameters such as blood
      pressure or heart rate upon initial presentation. The mean pericardial effusion
      scoring index was 6.0 for cases and 3.3 for controls showing a wide separation
      between the groups (P < 0.01). The area under the curve for receiver operator
      characteristic was 0.91 (95% confidence interval, 0.82-1.00). CONCLUSIONS: The
      pericardial effusion scoring index obtained at the initial presentation in
      patients without immediate hemodynamic compromise showed a high accuracy in
      identifying patients who required pericardial effusion drainage downstream.

PMID- 22595821
TI  - Society of chest pain centers:  what factors drive prehospital delay?

PMID- 22595822
TI  - Ethical issues in infertility treatment.
AB  - Two currently contentious domains in infertility treatment are discussed:
      assisted reproduction for same-sex couples and fertility preservation for women
      with cancer. Despite an increasing recognition of the rights of same-sex couples,
      in many countries they are still not eligible for assisted reproductive
      technology. The main justification for excluding same-sex couples from treatment
      is that the welfare of the future children would be compromised. Empirical
      evidence, however, shows that this is not the case. Another group of non
      infertile women seeking assistance from reproductive medicine are women with
      cancer who are at risk of impaired or lost fertility as a result of their illness
      or cancer treatment. In this field, the future holds many promising options.
      Several of these, however, are currently in an experimental phase, which elicits
      ethical concerns about participant recruitment and research participation of
      children.

PMID- 22595823
TI  - Complexity of the heat-soluble LEA proteome in Artemia species.
AB  - The brine shrimp Artemia is a well known stress tolerant invertebrate found on
      most continents. Under certain conditions females produce cysts (encysted
      gastrulae) that enter diapause, a state of obligate dormancy. During
      developmental formation of diapause embryos several different types of stress
      proteins accumulate in large amounts, including the late embryogenesis abundant
      (LEA) proteins. In this study we used a combination of heterologous group 3 LEA
      antibodies to demonstrate that the heat-soluble proteome of the cysts contains up
      to 12 distinct putative group 3 LEA proteins that complement the group 1 LEA
      proteins found previously. Most antibody-positive, heat-soluble proteins were
      larger than 50 kDa although antibody positive proteins of 20-38 kDa were also
      detected. Both nuclei and mitochondria had distinct complements of the putative
      group 3 LEA proteins. A few small group 3 LEA proteins were induced by cycles of
      hydration-dehydration along with one protein of about 62 kDa. The expression of
      group 3 LEA proteins, unlike members of group 1, was not restricted to encysted
      diapause embryos. Three to five putative group 3 LEA proteins were expressed in
      gravid females and in larvae. Cysts of different species from various geographic
      locations had distinct complements of group 3 LEA proteins suggesting rapid
      evolution of the LEA proteins or differences in the type of group 3 Lea genes
      expressed. Our results demonstrate the potential importance of group 3 LEA
      proteins in embryos and other life cycle stages of this animal extremophile.

PMID- 22595824
TI  - Nephrology quiz and questionnaire: transplantation.
AB  - Presentation of the Nephrology Quiz and Questionnaire (NQQ) has become an annual
      "tradition" at the meetings of the American Society of Nephrology. It is a very
      popular session judged by consistently large attendance. Members of the audience
      test their knowledge and judgment on a series of case-oriented questions prepared
      and discussed by experts. They can also compare their answers in real time, using
      audience response devices, to those of program directors of nephrology training
      programs in the United States, acquired through an Internet-based questionnaire.
      Topics presented here include transplantation issues. These cases, along with
      single best answer questions, were prepared by Dr. Hricik. After the audience
      responses, the "correct" and "incorrect" answers were then briefly discussed and
      the results of the questionnaire were displayed. This article aims to
      recapitulate the session and reproduce its educational value for a larger
      audience-that of the readers of the Clinical Journal of the American Society of
      Nephrology. Have fun.

PMID- 22595825
TI  - Prevalence and factors associated with hyperkalemia in predialysis patients
      followed in a low-clearance clinic.
AB  - BACKGROUND AND OBJECTIVES: Recent studies evaluated the prevalence of
      hyperkalemia and related risk factors in patients with CKD of various stages, but
      there is limited relevant information in predialysis patients. This study aimed
      to examine the prevalence and factors associated with hyperkalemia in the
      structured environment of a low-clearance clinic. DESIGN, SETTING, PARTICIPANTS,
      & MEASUREMENTS: In a cross-sectional fashion over a prespecified period of 4
      months, information on serum potassium and relevant laboratory variables,
      comorbidities, medications, and dietician input in patients with advanced CKD
      under follow-up in the low-clearance clinic of our department was recorded.
      Univariate and multiple logistic regression analyses were used to identify
      factors associated with serum potassium >= 5.5 meq/L. RESULTS: The study
      population consisted of 238 patients aged 66.2 +/- 4.2 years with estimated GFR
      of 14.5 +/- 4.8 ml/min per 1.73 m(2). The prevalence of hyperkalemia. defined as
      potassium > 5.0, >= 5.5, and >= 6.0 meq/L., was at 54.2%, 31.5%, and 8.4%,
      respectively. In univariate comparisons, patients with potassium >= 5.5 meq/L had
      significantly higher urea and lower estimated GFR and serum bicarbonate; also,
      they were more often using sodium bicarbonate and had received potassium
      education and attempts for dietary potassium lowering. Use of angiotensin
      converting enzyme inhibitors or angiotensin receptor blockers was not associated
      with hyperkalemia. In multivariate analyses, estimated GFR<15 ml/min per 1.73
      m(2) and sodium bicarbonate use were independently associated with hyperkalemia.
      CONCLUSIONS: The prevalence of hyperkalemia in predialysis patients with CKD is
      high. Even at this range of renal function, low estimated GFR seems to be the
      most important factor associated with hyperkalemia among the wide range of
      demographic, clinical, and laboratory characteristics studied.

PMID- 22595826
TI  - Health-related quality of life as a predictor of mortality among survivors of
      AKI.
AB  - BACKGROUND AND OBJECTIVES: This study examined the relationship between health
      related quality of life and subsequent mortality among AKI survivors treated with
      renal replacement therapy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
      Multivariable Cox regression models were used to assess the associations between
      Health Utilities Index Mark 3 (HUI3) and ambulation, emotion, cognition, and pain
      scores at 60 days and all-cause mortality at 1 year in 60-day AKI survivors
      (n=439 with evaluable HUI3 assessments) from a randomized multicenter study
      comparing less- with more-intensive renal replacement therapies. RESULTS: The
      median 60-day HUI3 index score was 0.32. Patients with evaluable HUI3 data who
      died between 60 days and 1 year (n=99) were more likely to have lower 60-day
      median HUI3 scores, higher comorbidity scores, and longer initial hospital stays,
      and they were more likely to be dialysis-dependent. A 0.1 higher HUI3 index score
      was associated with a 17% decrease (hazard ratio, 0.83; 95% confidence interval
      0.77-0.89) in all-cause mortality after controlling for clinical risk factors.
      Similar associations were observed for HUI3 ambulation, emotion, cognition, and
      pain attribute scores. CONCLUSIONS: Health-related quality of life measured by
      HUI3 is an independent predictor of mortality among survivors of AKI after
      adjusting for clinical risk variables. Poor ambulation and other health-related
      quality of life attributes are also associated with increased risk of death.
      Health-related quality of life may provide clinicians with additional information
      to help identify patients at high risk of mortality after AKI that required renal
      replacement therapy.

PMID- 22595827
TI  - A woman with recurrent calcium phosphate kidney stones.
AB  - Kidney stones composed predominantly (50% or more) of calcium phosphate
      constitute up to 10% of all stones and 15%-20% of calcium stones, 80% of which
      are composed of calcium oxalate. Calcium phosphate is a minor component of up to
      30% of calcium oxalate stones as well. The cause of calcium phosphate stones is
      often obscure but most often related to a high urine pH. Some patients with
      calcium phosphate stones may have incomplete renal tubular acidosis. Others have
      distal renal tubular acidosis characterized by hyperchloremic acidosis,
      hypocitraturia, and high urine pH. The use of carbonic anhydrase inhibitors such
      as acetazolamide, topiramate, and zonisamide leads to a similar picture.
      Treatment options to specifically prevent calcium phosphate stone recurrence have
      not been tested in clinical trials. Increases in urine volume and restriction of
      sodium intake to limit calcium excretion are important. Citrate supplementation
      is probably effective, although the concomitant increase in urine pH may increase
      calcium phosphate supersaturation and partially offset the inhibition of
      crystallization resulting from the increased urine citrate excretion and the
      alkali-associated reduction in urine calcium excretion. Thiazides lower urine
      calcium excretion and may help ensure the safety of citrate supplementation.

PMID- 22595828
TI  - Prognostic value of risk score and urinary markers in idiopathic membranous
      nephropathy.
AB  - BACKGROUND AND OBJECTIVES: Accurate prediction of prognosis may improve
      management of patients with idiopathic membranous nephropathy. This study
      compared the Toronto Risk Score and urinary low-molecular weight proteins.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: One hundred four patients with
      biopsy-proven idiopathic membranous nephropathy who presented between 1995 and
      2008 with a well-preserved kidney function and nephrotic range proteinuria were
      included. Urinary beta2-microglobulin and alpha1-microglobulin measurements were
      obtained by timed standardized measurements, and the Toronto Risk Score was
      calculated using data obtained from medical records. The endpoint was
      progression, which was defined as an increase in serum creatinine > 50% or > 25%
      with a concentration > 135 MUmol/L. RESULTS: Forty-nine patients showed
      progression. The area under the receiver-operating characteristics curve was 0.78
      (95% confidence interval = 0.69-0.88) for the risk score versus 0.80 (0.71-0.89)
      and 0.79 (0.71-0.88) for urinary beta2- and alpha1-microglobulin, respectively.
      Differences were not significant. Persistent proteinuria did not add accuracy to
      the Toronto Risk Score. Conversely, its accuracy was not reduced when data from
      the first 6 months of follow-up were used. Furthermore, a score based on GFR
      estimated with the six-variable Modification of Diet in Renal Disease equation,
      calculated in the first 6 months of follow-up, gave an area under the receiver
      operating characteristics curve of 0.83 (0.74-0.92), which was not statistically
      different from other markers. CONCLUSIONS: The prognostic accuracies of the
      Toronto Risk Score and urinary low-molecular weight proteins were not
      significantly different. The risk score can be calculated within 6 months of
      diagnosis, and a simplified risk score using estimated GFR-Modification of Diet
      in Renal Disease may be sufficient.

PMID- 22595829
TI  - Association of HLA genes with clinical outcomes of ANCA-associated vasculitis.
AB  - BACKGROUND AND OBJECTIVES: The HLA system plays a central role in the distinction
      between self antigens and non-self antigens. This study aimed to investigate the
      association between HLA genes and the outcomes of patients with ANCA-associated
      vasculitis (AAV). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study
      recruited 152 consecutive Chinese patients with AAV. The predictive value of the
      HLA alleles for renal outcome, response to treatment, and all-cause mortality
      were analyzed. RESULTS: The proportion of patients with treatment failure was
      significantly higher in DRB1*0405-positive patients than in DRB1*0405-negative
      patients (41.7% versus 12.9%; P=0.008; corrected P=0.02). After adjusting for the
      other potential predictors, DRB1*0405 was still an independent predictor for the
      poor response to treatment (hazard ratio [HR], 5.91; 95% confidence interval [95%
      CI], 1.23-28.52; P=0.03). Renal survival was significantly worse in patients with
      DRB1*0405 than those without DRB1*0405 (P<0.001; corrected P<0.001). After
      adjusting for the other potential predictors, DRB1*0405 was still an independent
      predictor for ESRD (HR, 5.50; 95% CI, 2.18-13.88; P<0.001). The probability of
      all-cause mortality in patients with DPB1*0402 was significantly higher than
      those without DPB1*0402 (P=0.02; corrected P=0.04). After adjusting for the other
      potential predictors, DPB1*0402 was still an independent predictor for all-cause
      mortality (HR, 2.52; 95% CI, 1.21-5.28; P=0.01). CONCLUSIONS: In AAV patients,
      DRB1*0405 might be an independent risk factor for the poor response to treatment
      and the deterioration of renal function, whereas DPB1*0402 might be an
      independent risk factor for all-cause mortality.

PMID- 22595830
TI  - Initial choice of antihypertensive on long-term cardiovascular outcomes in CKD.

PMID- 22595831
TI  - Remember to buy milk on the way home! A meta-analytic review of prospective
      memory in mild cognitive impairment and dementia.
AB  - Prospective memory (PM) is the ability to remember to execute delayed intentions.
      Previous studies indicate that PM is impaired in persons with mild cognitive
      impairment (MCI) and dementia, but the extent, nature, and cognitive correlates
      are unclear. A meta-analytic review was, therefore, performed (literature search
      1990 to July 2011) on case-control studies on PM in dementia (10 studies, 336
      patients, 505 controls) and MCI (7 studies, 225 patients, 253 controls).
      Differences between event-based and time-based PM and between measures of
      prospective and retrospective memory were examined, as well as correlations with
      other cognitive functions. Results showed that patients with dementia or MCI
      exhibit large deficits in PM (Hedges' d -1.62 [95% confidence interval -1.98 to 
      1.27; p < .0001] for dementia; -1.24 [-1.51 to -0.995; p < .0001] for MCI;
      difference dementia vs. MCI: QM = 1.94, p = .16). Impairments were comparable in
      size for event-based and time-based PM (p > .05), as well as for prospective and
      retrospective memory (p > .05). PM showed modest correlations with measures of
      retrospective memory (median r = 0.27) and executive functioning (median r =
      0.30). PM appears a valid construct in neuropsychological assessment in patients
      with dementia or MCI, but more insight is needed in the optimal characteristics
      of PM tasks to be used in clinical practice.

PMID- 22595832
TI  - Radical kinetics in sub- and supercritical carbon dioxide: thermodynamic rate
      tuning.
AB  - We report rate constants for muonium addition to 1,1-difluoroethylene (vinylidene
      fluoride) in CO2 at 290-530 K, 40-360 bar, and 0.05-0.90 g cm(-3). Rate constants
      are mapped against their thermodynamic conditions, demonstrating the kinetic
      tuning ability of the solvent. The reaction exhibits critical slowing near
      conditions of maximum solvent isothermal compressibility, where activation
      volumes of unprecedentedly large magnitudes on the order of +/-10(6) cm(3) mol(
      1) are observed. Such values are suggestive of pressure being a significant
      parameter for tuning fluorolkene reactivity. 

PMID- 22595833
TI  - Intrinsically high-Q dynamic AFM imaging in liquid with a significantly extended
      needle tip.
AB  - Atomic force microscope (AFM) probe with a long and rigid needle tip was
      fabricated and studied for high Q factor dynamic (tapping mode) AFM imaging of
      samples submersed in liquid. The extended needle tip over a regular commercially
      available tapping-mode AFM cantilever was sufficiently long to keep the AFM
      cantilever from submersed in liquid, which significantly minimized the
      hydrodynamic damping involved in dynamic AFM imaging of samples in liquid.
      Dynamic AFM imaging of samples in liquid at an intrinsic Q factor of over 100 and
      an operational frequency of over 200 kHz was demonstrated. The method has the
      potential to be extended to acquire viscoelastic material properties and provide
      truly gentle imaging of soft biological samples in physiological environments.

PMID- 22595834
TI  - Does aging of mesenchymal stem cells limit their potential application in
      clinical practice?
AB  - Mesenchymal stem cells (MSCs) are in the center of attention of many
      investigators due to easy isolation from many tissues. MSC capability to
      differentiate into many cell types makes them a starting point of many new
      therapies, especially in tissue engineering. However, understanding the process
      of MSC aging is crucial for selecting donors for cellular therapies, which is
      necessary for successful treatment. Cell changes can be divided into three major
      groups. Changes which affect their proliferate rate, differentiation capability
      and genome stability lead to decrease of their usefulness in new therapies. There
      are many tools that can be used to describe and measure some features of aging in
      MSCs but the essence of this process is still unclear. The aim of this review is
      to take a deep look into the influence of donor age and in vitro aging on MSC
      properties.

PMID- 22595835
TI  - Heavy metallic oxide nanoparticles for enhanced sensitivity in semiconducting
      polymer x-ray detectors.
AB  - Semiconducting polymers have previously been used as the transduction material in
      x-ray dosimeters, but these devices have a rather low detection sensitivity
      because of the low x-ray attenuation efficiency of the organic active layer.
      Here, we demonstrate a way to overcome this limitation through the introduction
      of high density nanoparticles having a high atomic number (Z) to increase the x
      ray attenuation. Specifically, bismuth oxide (Bi(2)O(3)) nanoparticles (Z = 83
      for Bi) are added to a poly(triarylamine) (PTAA) semiconducting polymer in the
      active layer of an x-ray detector. Scanning electron microscopy (SEM) reveals
      that the Bi(2)O(3) nanoparticles are reasonably distributed in the PTAA active
      layer. The reverse bias dc current-voltage characteristics for PTAA-Bi(2)O(3)
      diodes (with indium tin oxide (ITO) and Al contacts) have similar leakage
      currents to ITO/PTAA/Al diodes. Upon irradiation with 17.5 keV x-ray beams, a
      PTAA device containing 60 wt% Bi(2)O(3) nanoparticles demonstrates a sensitivity
      increase of approximately 2.5 times compared to the plain PTAA sensor. These
      results indicate that the addition of high-Z nanoparticles improves the
      performance of the dosimeters by increasing the x-ray stopping power of the
      active volume of the diode. Because the Bi(2)O(3) has a high density, it can be
      used very efficiently, achieving a high weight fraction with a low volume
      fraction of nanoparticles. The mechanical flexibility of the polymer is not
      sacrificed when the inorganic nanoparticles are incorporated.

PMID- 22595836
TI  - US military medical support after the earthquake in Managua, Nicaragua.

PMID- 22595837
TI  - Isobaric cross-sequence labeling of peptides by using site-selective N-terminus
      dimethylation.
AB  - Highly site-selective dimethyl labeling of N-terminus of peptides has been
      obtained by adjusting the acidic strength of the reaction solution. And this
      selective labeling strategy combined with the use of different isotope
      formaldehyde reagents has been successfully used in the proteome quantification
      by using the isobaric peptide cross-sequence labeling method, which would play
      increasingly important roles in the clinical diagnosis, especially in the
      discovery of biomarkers for diseases.

PMID- 22595838
TI  - Modelling piloted ignition of wood and plastics.
AB  - To gain insight in the startup of an incinerator, this article deals with piloted
      ignition. A newly developed model is described to predict the piloted ignition
      times of wood, PMMA and PVC. The model is based on the lower flammability limit
      and the adiabatic flame temperature at this limit. The incoming radiative heat
      flux, sample thickness and moisture content are some of the used variables. Not
      only the ignition time can be calculated with the model, but also the mass flux
      and surface temperature at ignition. The ignition times for softwoods and PMMA
      are mainly under-predicted. For hardwoods and PVC the predicted ignition times
      agree well with experimental results. Due to a significant scatter in the
      experimental data the mass flux and surface temperature calculated with the model
      are hard to validate. The model is applied on the startup of a municipal waste
      incineration plant. For this process a maximum allowable primary air flow is
      derived. When the primary air flow is above this maximum air flow, no ignition
      can be obtained.

PMID- 22595839
TI  - Electricity generation from cattle dung using microbial fuel cell technology
      during anaerobic acidogenesis and the development of microbial populations.
AB  - A microbial fuel cell (MFC) was constructed to investigate the possible
      generation of electricity using cattle dung as a substrate. After 30 days of
      operation, stable electricity was generated, and the maximum volumetric power
      density was 0.220 W/m(3). The total chemical oxygen demand (TCOD) removal and
      coulombic efficiency (CE) of the MFC reached 73.9+/-1.8% and 2.79+/-0.6%,
      respectively, after 120 days of operation. Acetate was the main metabolite in the
      anolyte, and other volatile fatty acids (VFAs) (propionate and butyrate) were
      present in minor amounts. The PCR-DGGE analysis indicated that the following five
      groups of microbes were present: Proteobacteria, Bacteroides, Chloroflexi,
      Actinobacteria and Firmicutes. Proteobacteria and Firmicutes were the dominant
      phyla in the sample; specifically, 36.3% and 24.2% of the sequences obtained were
      Proteobacteria and Firmicutes, respectively. Clostridium sp., Pseudomonas luteola
      and Ochrobactrum pseudogrignonense were the most dominant groups during the
      electricity generation process. The diversity of archaea dramatically decreased
      after 20 days of operation. The detected archaea were hydrogenotrophic
      methanogens, and the Methanobacterium genus disappeared during the periods of
      stable electricity generation via acidogenesis.

PMID- 22595840
TI  - Which method is best for imaging of anal sphincter defects?

PMID- 22595841
TI  - High-throughput arrays identify distinct genetic profiles associated with lymph
      node involvement in rectal cancer.
AB  - BACKGROUND: Preoperative clinical diagnosis of lymph node involvement guides
      treatment decisions for rectal cancer. Unfortunately, clinical staging still
      suffers from a lack of accuracy. OBJECTIVE: The aim of this study was to evaluate
      objective genetic differences in primary rectal cancers with and without
      associated lymph node metastasis. DESIGN: cDNA microarrays were generated from
      fresh-frozen tumors. Normalized data underwent global unsupervised hierarchical
      clustering analysis, and discriminating genes were mapped. Top discriminating
      genes were compared between stage II and III rectal cancers by use of an
      empirical Bayes 2 group t test with the Statistical Analysis of Microarrays and
      the Reproducibility-Optimized Test Statistic software separately to guide data
      reduction and deal with the difficulties of simultaneous statistical inference.
      Ingenuity Pathways Analysis software was used to analyze discriminating genes in
      terms of function and biological processes. PATIENTS: Fifty-five patients with
      stage II and 22 patients with stage III rectal adenocarcinomas not treated with
      chemoradiation were included. RESULTS: Two major unsupervised clusters emerged
      representing stage II and III cancers. In 1 cluster, 11 of 12 patients (92%) had
      stage III cancer; in the other cluster, 54 of 65 patients (83%) had stage II (p <
      0.001). Five significantly differentially expressed genes characterized the stage
      III cluster: interleukin-8, 3-hydroxy-3-methylglutaryl coenzyme A synthase,
      carbonic anhydrase, ubiquitin, and cystatin (all p < 0.05). Of the 12 patients
      with differential expression of the 5 marker genes, only one had stage II cancer.
      Fifty-four of 55 stage II patients clustered with alternative expression patterns
      of the predictor genes. Differentially expressed genes are related to cancer
      associated processes, pathways, and networks. LIMITATIONS: The identified gene
      signatures have not yet been validated in independent patient populations.
      CONCLUSIONS: Distinct gene expression signatures from primary rectal
      adenocarcinomas can help differentiate the presence or absence of lymph node
      metastases. These data are informative, and validation of this gene signature may
      provide a novel approach for more appropriate individualized treatment selection.

PMID- 22595842
TI  - Converting emergency pilonidal abscess into an elective procedure.
AB  - BACKGROUND: Improvements in outcome after surgery for elective pilonidal sinus
      disease have yet to be matched for those presenting with acute disease.
      Traditional approaches to the management of acute pilonidal abscess have been
      associated with slow healing and significant loss of working time. OBJECTIVE: The
      aim of this study was to report our approach in which a temporizing intervention
      allows subsequent definitive treatment with low morbidity. DESIGN: This article
      presents a prospective cohort study. SETTING: This study was performed in acute
      admissions to the Surgical Unit in York Teaching Hospital. PATIENTS: Patients
      presenting with acute pilonidal abscess, not septic, immune-compromised, or
      diabetic, and without skin necrosis, underwent aspiration on the surgical ward.
      INTERVENTION: Aspiration of pilonidal abscess under local anesthetic was
      performed with the use of a wide-bore needle. The abscess cavity was drained to
      dryness, samples were sent to the laboratory for microbiology, and empirical oral
      antibiotics were commenced, covering anaerobes and aerobes. Review was arranged
      for within 7 days to plan elective excision and primary closure of the underlying
      pilonidal sinus. MAIN OUTCOME MEASURES: The primary outcomes measured were the
      number of days required to return to normal activities, response to treatment,
      and any residual inflammation. RESULTS: Fifty-six patients were referred with
      acute pilonidal abscess. Forty patients met the criteria for aspiration and
      empirical antibiotic treatment. All were allowed to go home the same day and were
      reviewed within a median of 5 days. Thirty-eight (38/40) patients demonstrated
      complete resolution of acute inflammation and were back to normal activities the
      following day. Fifteen patients subsequently underwent day-case excision and
      primary closure at a median of 9 weeks. Another 13 are awaiting surgery, and 10
      patients have declined further treatment. Two (2/40) patients did not respond,
      one of whom did not receive the appropriate antibiotics. Both were managed with
      incision and drainage. CONCLUSIONS: Aspiration and antibiotic management of
      pilonidal abscess is effective in 95% of acute cases in preventing the need for
      emergent laying open and allows for subsequent elective surgery.

PMID- 22595843
TI  - Detection of anal sphincter defects in female patients with fecal incontinence: 
      a comparison of 3-dimensional transperineal ultrasound and 2-dimensional endoanal
      ultrasound.
AB  - BACKGROUND: Endoanal ultrasound is widely used for the detection of external and
      internal anal sphincter defects in patients with fecal incontinence. Recently, 3
      dimensional transperineal ultrasound has been introduced as a noninvasive imaging
      method for the detection of these sphincter defects. OBJECTIVE: This study was
      designed to assess agreement between 3-dimensional transperineal ultrasound and 2
      dimensional endoanal ultrasound regarding the detection of anal sphincter defects
      in women with fecal incontinence. DESIGN: This study was designed as a
      prospective observational study. SETTINGS: The study took place in a university
      hospital. PATIENTS: Between October 2008 and June 2009, all women with concerns
      of fecal incontinence underwent 2-dimensional endoanal ultrasound as well as 3
      dimensional transperineal ultrasound. MAIN OUTCOME MEASURES: The main outcome
      measures are the presence of external and internal anal sphincter defects.
      RESULTS: Fifty-five patients were included. External and internal anal sphincter
      defects were observed with 2-dimensional endoanal ultrasound in 27 (49%) and 15
      (27%) patients. Three-dimensional transperineal ultrasound detected an external
      and internal sphincter defect in 19 (35%) and 16 (29%) patients. The Cohen kappa
      coefficient for the detection of external (kappa = 0.63) and internal (kappa =
      0.78) anal sphincter defects was good. LIMITATIONS: This study's limitations
      include the absence of a surgical examination as the reference standard in the
      determination of sphincter defects. CONCLUSION: This study shows good agreement
      between 3-dimensional transperineal ultrasound and 2-dimensional endoanal
      ultrasound regarding the detection of anal sphincter defects. Based on these
      data, 3-dimensional transperineal ultrasound might be considered as a valuable
      alternative noninvasive investigation method.

PMID- 22595844
TI  - Quality of life after surgery for colon cancer in patients with Lynch syndrome:
      partial versus subtotal colectomy.
AB  - BACKGROUND: Lynch syndrome is a disorder caused by mismatch repair gene
      mutations. Mutation carriers have a high risk of developing colorectal cancer. In
      patients with Lynch syndrome in whom colon cancer has been diagnosed, in general,
      subtotal colectomy instead of partial colectomy is recommended because of the
      substantial risk of metachronous colorectal cancer. However, the effect of more
      extensive surgery on quality of life and functional outcome is unknown.
      OBJECTIVE: The aim of this study was to investigate quality of life and
      functional outcome in patients with Lynch syndrome after partial colectomy and
      subtotal colectomy. DESIGN: This is a nationwide cross-sectional study in the
      Netherlands. SETTINGS: Two quality-of-life questionnaires (Short Form-36 and The
      European Organization for Research and Treatment of Cancer Colorectal Cancer
      specific Quality of Life Questionnaire Module) and a functional outcome
      questionnaire (Colorectal Functional Outcome) were used. PATIENTS: Patients with
      Lynch syndrome who underwent surgery for colon cancer were included. MAIN OUTCOME
      MEASURES: The primary outcomes measured were quality of life and functional
      outcome. RESULTS: Questionnaires were sent to 192 patients with Lynch syndrome
      who underwent surgery for colorectal cancer. A total of 136 patients returned the
      questionnaire (response rate, 71%). Eighteen patients with rectal cancer, 9
      patients with a permanent ileostomy, and 5 patients with an IPAA were excluded.
      Fifty-one patients underwent partial colectomy, and 53 underwent subtotal
      colectomy. None of the scales of the Short Form-36 survey showed a significant
      difference. Analysis of the Colorectal Functional Outcome questionnaire revealed
      that, after subtotal colectomy, patients have a significantly higher stool
      frequency (p <= 0.01) and a significantly higher score on stool-related aspects
      (p = 0.06) and social impact (p = 0.03). The European Organization for Research
      and Treatment of Cancer Colorectal Cancer-specific Quality of Life Questionnaire
      Module presented more problems with defecation after subtotal colectomy (p <=
      0.01). LIMITATIONS: Certain selection bias cannot be ruled out. CONCLUSIONS:
      Although functional outcome is worse after subtotal colectomy than after partial
      colectomy, generic quality of life does not differ after the 2 types of surgery
      in Lynch syndrome. When discussing the options for surgery with the patient, all
      advantages and disadvantages of both surgical procedures, including quality of
      life and functional outcome, should be discussed.

PMID- 22595845
TI  - Laparoscopic anterior rectopexy to the promontory for full-thickness rectal
      prolapse in 175 consecutive patients: short- and long-term follow-up.
AB  - BACKGROUND: There are multiple procedures to treat full-thickness rectal
      prolapse. No consensus exists as to the best surgical option. All procedures have
      a significant recurrence rate. OBJECTIVE: The aim of this study was to report
      short- and long-term technical results following laparoscopic removal of the
      Douglas pouch peritoneum and anterior rectopexy in patients with total rectal
      prolapse. DESIGN: This study is a prospective evaluation of consecutive patients.
      SETTINGS: This investigation was conducted at a single academic colorectal unit.
      PATIENTS: Between May 1996 and June 2009, 175 consecutive patients (17 males)
      with a mean age of 58 years (range, 16-94) were operated on. INTERVENTION: The
      Douglas pouch peritoneum was excised, 2 synthetic meshes were fixated to the
      anterior part of the lower rectum with five 4-mm staples and to the promontory
      with 3 spiked chromium staples, and the peritoneum was closed over the meshes to
      isolate them from the abdominal cavity. MAIN OUTCOME MEASURES: Patients were
      reviewed at months 1, 6, 12, and then annually. Mortality, morbidity, and
      recurrence were analyzed. Median follow-up was 74 months (range, 24-181).
      Recurrence rate was calculated according to the Kaplan-Meier method. RESULTS: :
      There was no mortality. Morbidity (5.1%) consisted in temporary brachial plexus
      palsy in 2 cases, urinary infection in 3 cases, ureteral lesion in 1 patient
      having had a previous bone graft on the promontory for spondylolisthesis (JJ
      catheter), and perforation of the small bowel because of adhesions (laparoscopic
      suture) in 1 case. One patient presented with a rectal erosion at month 9
      (transanal removal of the mesh). Two patients presented with a recurrence of the
      rectal prolapse at months 6 and 24 (recurrence rate of 3% at 5 years) that was
      treated with anal artificial sphincter in one and redo operation in the other.
      CONCLUSION: Laparoscopic removal of the Douglas pouch peritoneum and rectopexy to
      the promontory is a safe and efficient procedure to treat full-thickness rectal
      prolapse.

PMID- 22595846
TI  - Perineal rectosigmoidectomy for primary and recurrent rectal prolapse:  are the
      results comparable the second time?
AB  - BACKGROUND: The surgical approach to recurrent full-thickness rectal prolapse
      after perineal rectosigmoidectomy is complicated by recurrent prolapse. The
      majority of patients who undergo perineal rectosigmoidectomy are elderly with
      comorbidities. Therefore, redo perineal rectosigmoidectomy is usually selected to
      avoid postoperative complications. OBJECTIVE: This study aimed to evaluate the
      safety and efficacy of redo perineal rectosigmoidectomy for recurrent full
      thickness rectal prolapse. DESIGN: This is a retrospective cohort study. SETTING:
      This study was conducted at Cleveland Clinic Florida, from January 2000 to March
      2009. PATIENTS: One hundred thirty-six patients (129 women), mean age 78 (range,
      31-98) years, were included in the study; 113 patients with full-thickness rectal
      prolapse underwent primary perineal rectosigmoidectomy, and 23 patients with
      recurrent full-thickness rectal prolapse underwent redo perineal
      rectosigmoidectomy. INTERVENTIONS: All patients underwent perineal
      rectosigmoidectomy. MAIN OUTCOME MEASURES: Perioperative outcomes, recurrence
      curves, and risk of recurrence were compared between the 2 groups. Age, anterior
      compartment prolapse, concurrent levatorplasty, and length of bowel resection
      were analyzed to identify factors potentially influencing recurrence. RESULTS:
      Both groups had comparable demographics, BMI, and ASA scores. Operative time,
      blood loss, length of bowel resection, hospital stay, and follow-up (mean, 42.5
      months) were similar in both groups. There was no significant difference in
      overall complication rates (redo perineal rectosigmoidectomy 17.4% vs. primary
      perineal rectosigmoidectomy 16.8%; p = 1.00). The recurrence rate for full
      thickness rectal prolapse was significantly higher for redo perineal
      rectosigmoidectomy than primary perineal rectosigmoidectomy (39% vs. 18%; p =
      0.007). None of the factors analyzed was associated with recurrence in either
      group. LIMITATIONS: This study was limited by its retrospective methodology. In
      addition, functional outcomes were not evaluated, because many of the patients
      died during the follow-up period or were unavailable because of advanced age.
      CONCLUSIONS: Redo perineal rectosigmoidectomy is as safe and feasible as primary
      perineal rectosigmoidectomy in elderly and fragile patients with recurrent full
      thickness rectal prolapse. However, the re-recurrence rate for full-thickness
      rectal prolapse is substantially higher for redo perineal rectosigmoidectomy than
      primary perineal rectosigmoidectomy.

PMID- 22595847
TI  - Evaluation of bowel function and fecal continence in 594 Finnish individuals aged
      4 to 26 years.
AB  - BACKGROUND: Limited information exists on what constitutes normal bowel function
      in children and adolescents. This information is essential for determining
      outcomes of surgery for anorectal malformations and other colonic disorders.
      OBJECTIVE: The aim of this study was to define bowel function and fecal
      continence in a large sample of individuals aged 4 to 26 years. DESIGN: This
      investigation is a cross-sectional cohort study. SETTINGS: Five hundred ninety
      four individuals aged 4 to 26 years were randomly selected from the population
      register of Finland. Participants anonymously answered a previously validated 7
      item postal questionnaire on bowel function. MAIN OUTCOME MEASURES: The primary
      outcomes measured were bowel function score, fecal continence, stooling
      frequency, constipation, and social problems in relation to bowel function.
      RESULTS: Recognition of the need to defecate was well established by age 4, but
      the ability to hold back defecation improved with age. Fecal accidents decreased
      from 11% in preschool children to 2% by 13 to 17 years (p = 0.02). Fecal staining
      of underwear was common (33%); the prevalence of soiling decreased with age.
      Stooling frequency was normal in 92%. Constipation was more common in females.
      Problems restricting social life in relation to bowel function were rare (0.5%).
      CONCLUSIONS: The fine-tuning of fecal continence continues to develop during
      childhood. Minor soiling is common in healthy individuals. Because of the changes
      with age, the evaluation of functional outcomes in patients who have undergone
      surgical treatment of anorectal malformations or other colonic disorders should
      include comparison with data from age-matched controls.

PMID- 22595849
TI  - Hydroxymethylglutaryl-coenzyme a synthase 2 expression is associated with
      chemoradiotherapy responses in colorectal cancer.
AB  - BACKGROUND: Preoperative chemoradiotherapy has become a standard treatment
      modality for locally advanced rectal cancer. Favorable long-term outcomes have
      been reported for patients with good responses to chemoradiotherapy. Therefore,
      predictive factors for chemoradiotherapy responses can be useful for their
      applicability to risk-adaptive therapy in patients with colorectal cancer.
      OBJECTIVE: The aim of this study was to investigate whether hydroxymethylglutaryl
      coenzyme A synthase 2, a key enzyme in ketogenesis, is associated with the
      responses of colorectal cancer cells to chemoradiotherapy. DESIGN:
      Hydroxymethylglutaryl-coenzyme A synthase 2 was identified by a 2-dimensional gel
      electrophoresis -based proteome analysis. It was analyzed in 12 colorectal cancer
      cells for associations with radiation or 5-fluorouracil susceptibility by Western
      blotting, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium Bromide assay, and
      small interfering RNA transfection. Then, tumor tissues obtained from 45 patients
      with rectal cancer before chemoradiotherapy were analyzed by Western blotting for
      associations with chemoradiotherapy responses. RESULTS: Expression of
      hydroxymethylglutaryl-coenzyme A synthase 2 was significantly correlated with
      intrinsic radiation resistance of 12 cancer cells. Hydroxymethylglutaryl-coenzyme
      A synthase 2 expression was significantly affected by treatment with either 5
      fluorouracil or radiation depending on cell types. The artificial suppression of
      hydroxymethylglutaryl-coenzyme A synthase 2 did not result in the change of
      chemoradiation susceptibility in colorectal cancer cells. Nevertheless, in
      multivariate analyses, hydroxymethylglutaryl-coenzyme A synthase 2 expression in
      rectal cancer tissues was shown to be a significant predictive factor for
      chemoradiotherapy responses, as evaluated in terms of tumor regression grade and
      downstaging. LIMITATIONS: Overall findings in vitro showed that the expression
      level of hydroxymethylglutaryl-coenzyme A synthase 2 was highly variable
      depending on colon cancer cell types, and it cannot directly affect on
      chemoradiotherapy responses. The molecular mechanism underpinning the association
      between hydroxymethylglutaryl-coenzyme A synthase expression and
      chemoradiotherapy responses needs to be elucidated through future research.
      CONCLUSIONS: Hydroxymethylglutaryl-coenzyme A synthase 2 was associated with the
      effects of chemoradiotherapy on human colorectal cancer cells. Pretreatment
      levels of hydroxymethylglutaryl-coenzyme A synthase 2 in rectal cancer may be
      useful in predicting the responses to chemoradiotherapy.

PMID- 22595848
TI  - Chromosomal copy number alterations are associated with persistent lymph node
      metastasis after chemoradiation in locally advanced rectal cancer.
AB  - BACKGROUND: Lymph node metastasis is an important indicator of oncologic outcome
      for patients with rectal cancer. Identifying predictive biomarkers of lymph node
      metastasis could therefore be clinically useful. OBJECTIVE: The aim of this study
      was to assess whether chromosomal copy number alterations can assist in
      predicting persistent lymph node metastasis in patients with locally advanced
      rectal cancer treated with preoperative chemoradiation therapy. DESIGN: This is a
      nonrandomized, prospective phase II study. SETTING: This study took place in a
      multi-institutional setting. PATIENTS: Ninety-five patients with stage II (cT3-4,
      cN0) or stage III (any cT, cN1-2) rectal cancer were included. INTERVENTION:
      Patients were treated with preoperative chemoradiation therapy followed by total
      mesorectal excision. Pretreatment biopsy tumor DNA and surgical margin control
      DNA were extracted and analyzed by oligonucleotide array-based comparative
      genomic hybridization. Chromosomal copy number alterations were correlated with
      persistent lymph node metastasis. Finally, a model for predicting persistent
      lymph node metastasis was built. MAIN OUTCOME MEASURES: The primary outcomes
      assessed were whether chromosomal copy number alterations are associated with
      persistent lymph node metastasis in patients with rectal cancer and the accuracy
      of oligonucleotide array-based comparative genomic hybridization for predicting
      lymph node metastasis. RESULTS: Twenty-five of 95 (26%) patients had lymph node
      metastasis after chemoradiation. Losses of 28 chromosomal regions, most notably
      in chromosome 4, were significantly associated with lymph node metastasis. Our
      predictive model contained 65 probes and predicted persistent lymph node
      metastasis with 68% sensitivity, 93% specificity, and positive and negative
      predictive values of 77% and 89%. The use of this model accurately predicted
      lymph node status (positive or negative) after chemoradiation therapy in 82 of 95
      patients (86%). LIMITATIONS: The patient cohort was not completely homogeneous,
      which may have influenced their clinical outcome. In addition, although we
      performed rigorous, statistically sound internal validation, external validation
      will be important to further corroborate our findings. CONCLUSIONS: Copy number
      alterations can help identify patients with rectal cancer who are at risk of
      lymph node metastasis after chemoradiation.

PMID- 22595850
TI  - Orthovoltage intraoperative radiotherapy for locally advanced and recurrent
      colorectal cancer.
AB  - BACKGROUND: Locally advanced and recurrent colorectal cancers pose a significant
      therapeutic challenge. Orthovoltage intraoperative radiotherapy provides one
      potential means of improving disease control at the time of surgery. OBJECTIVE:
      This study sought to analyze outcomes and identify prognostic factors of patients
      treated with orthovoltage intraoperative radiotherapy for locally advanced or
      recurrent colorectal cancer. DESIGN AND SETTING: This study is a retrospective
      chart review conducted at a tertiary medical center. PATIENTS: Between January
      1990 and July 2009, 55 patients underwent intraoperative radiotherapy to a total
      of 61 sites for locally advanced (n = 14) or recurrent (n = 41) cancers of colon
      (n = 18) or rectum/rectosigmoid junction (n = 37). INTERVENTIONS: Median dose was
      12 Gy (range, 7.5-20 Gy). Among locally advanced rectal/rectosigmoid cases,
      surgery included abdominoperineal resection (n = 3) or low anterior resection (n
      = 9). Seven treated sites had gross residual (R2) disease, 28 had pathologic or
      clinical microscopic residual disease (R1), and 15 were complete resections (R0).
      Treated sites included sacrum (n = 22), anterior pelvis/pelvic sidewall (19),
      sacrum and sidewall (n = 1), aortic bifurcation (n = 2), vaginal cuff (n = 2),
      psoas (n = 3), perivesicular region (n = 2), and other (n = 10). MAIN OUTCOMES
      MEASURES: Outcomes measures included in-field local control, locoregional
      control, overall survival, and grade >=3 toxicity. RESULTS: At a median follow-up
      of 27 months (range, 4-237) among living patients, 2-year Kaplan-Meier estimates
      of in-field local control, locoregional control, and overall survival were 69%,
      51%, and 59%. Margin status predicted for improved locoregional control (p =
      0.01) and overall survival (p = 0.01). Seventeen patients (31%) developed a grade
      3 to 5 toxicity following surgery with intraoperative radiotherapy. LIMITATIONS:
      This study was limited by its retrospective nature and relatively small sample
      size. CONCLUSIONS: Local control with intraoperative radiotherapy for locally
      advanced and recurrent colorectal cancers is good despite the high risk of
      residual disease. Among carefully selected patients, multimodality regimens
      including intraoperative radiotherapy may permit long-term survival.

PMID- 22595851
TI  - Alcohol consumption and colorectal cancer in a Mediterranean population: a case
      control study.
AB  - BACKGROUND: Alcohol is considered to be a cocarcinogen or a tumor promoter, and
      various studies have shown a linear dose-dependent association between alcohol
      consumption and colorectal cancer. However, a few studies suggest that moderate
      alcohol consumption may have a protective effect, similar to that in
      cardiovascular disease. OBJECTIVE: The aim of this study was to evaluate the
      relationship of colorectal cancer to quantity and type of alcohol consumed.
      DESIGN: This was case-control study. SETTINGS: The study was conducted in the
      area of Attica, Greece. PARTICIPANTS: A total of 250 consecutive patients with a
      first diagnosis of colorectal cancer were matched for age group and sex with 250
      controls recruited from the community. The mean age was 63 (SD, 12) years for the
      patient group (147 men, 59%; 103 women, 41%) and 55 (SD, 13) years for the
      control group (112 men; 44.8%; 138 women, 55.2%). MAIN OUTCOME MEASURES:
      Questionnaires were administered by trained interviewers to assess
      sociodemographic, clinical, and lifestyle characteristics, in addition to dietary
      habits and quantity and type of alcoholic beverages usually consumed during the
      preceding year. Adherence to the Mediterranean diet was evaluated with the
      MedDietScore (theoretical range, 0-55). RESULTS: With intake of less than 12 g of
      alcohol per day as the reference, moderate alcohol intake (12-35 g/day) was
      associated with a significantly decreased likelihood of colorectal cancer in men
      (OR, 0.35; 95% CI, 0.16-0.74) and in women (OR, 0.40; 95% CI, 0.18-0.91). High
      alcohol intake (more than 48 g/day) was associated with an increased likelihood,
      which was significant in men (OR, 3.45; 95% CI, 1.35-8.83) but not in women (OR,
      3.40; 95% CI, 0.50-22.92). Drinking red wine was associated with reduced odds of
      colorectal cancer, significant in men (OR, 0.47; 95% CI, 0.23-0.96) but not in
      women (OR, 0.54; 95% CI, 0.23-1.30). None of the associations between other
      beverage types and colorectal cancer were significant. Adherence to the
      Mediterranean diet was independently associated with lower odds of colorectal
      cancer overall (p < 0.001), in men (OR, 0.90; 95% CI, 0.83-0.97), and in women
      (OR, 0.87; 95% CI, 0.80-0.94). LIMITATIONS: The major limitations of this study
      included the inability of a case-control design to determine causation and the
      potential for recall bias. CONCLUSIONS: The association between quantity of
      alcohol consumed and the presence of colorectal cancer followed a J-shaped curve.
      While demonstrating the detrimental effect of consuming large amounts of alcohol,
      the results of this study suggest that moderate alcohol consumption exerts a
      protective effect on colorectal cancer in both men and women, possibly related to
      the effects of red wine.

PMID- 22595852
TI  - Percutaneous tibial nerve stimulation for fecal incontinence:  a video
      demonstration.
AB  - BACKGROUND: Fecal incontinence is an increasingly common condition with
      significant negative impact on quality on life and health care resources. It
      frequently presents a therapeutic challenge to clinicians. Emerging evidence
      suggests that percutaneous tibial nerve stimulation is an effective treatment for
      fecal incontinence with the added benefit of being minimally invasive and cost
      effective. METHOD: Pursuant to the preliminary report of our early experience of
      percutaneous tibial nerve stimulation in patients with fecal incontinence
      published in this journal in 2010, in this dynamic article, we now describe and
      demonstrate the actual technique that can be performed in a nurse-led clinic or
      outpatient or community setting. CONCLUSION: Percutaneous tibial nerve
      stimulation is a technically simple procedure that can potentially be performed
      in an outpatient or community setting. The overall early success rate of 68%
      following its use reported by our unit compares favorably with the success rate
      following other forms of neuromodulation, including sacral nerve stimulation.
      When completed, our long-term outcome data will provide further information on
      the efficacy of tibial nerve stimulation in a larger cohort of patients (n >
      100). Future studies, including our currently planned randomized controlled trial
      of percutaneous tibial nerve stimulation vs sham stimulation, will provide
      controlled efficacy data and may provide information on its exact mechanism of
      action.

PMID- 22595853
TI  - Comparison of conventional and nonconventional strictureplasties in Crohn's
      disease:  a systematic review and meta-analysis.
AB  - BACKGROUND: The Heineke-Mikulicz and Finney techniques are conventional
      strictureplasties that have been used to manage short (<10 cm) and medium-length
      (>10 cm and <20 cm) strictures from Crohn's disease. Nonconventional
      strictureplasty techniques have emerged to facilitate bowel conservation for
      atypical strictures. These techniques include the modified Finney, combined
      Heineke-Mikulicz and Finney, modified Heineke-Mikuliczs, Michelassi, and
      modifications of it and others. OBJECTIVE: The aim of this study is to compare
      conventional vs nonconventional strictureplasties with respect to short-term
      complications and long-term results. DATA SOURCES AND STUDY SELECTION: A MEDLINE
      search was performed using "Crohn's disease", "surgical therapy",
      "strictureplasty", "complications", "reoperation", and "recurrence" as medical
      subject headings. Studies conducted between 1975 and June 31, 2010 were found via
      PubMed, Ovid, Embase, and Cochrane databases and categorized into 3 groups. These
      groups consist of centers performing conventional strictureplasties,
      nonconventional strictureplasties, or both. Studies with at least 3 patients were
      reviewed. INTERVENTIONS: A mixed-effects meta-analysis for each outcome was
      performed by use of Supermix software by SSI Scientific Software International.
      MAIN OUTCOME MEASURES: We focused on immediate and long-term complication rates
      among the groups. The 6 immediate complications include small-bowel obstructions,
      sepsis, other infections, reoperations, early postoperative GI bleeds, and other
      early complications. The 5 long-term complications include recurrent strictures,
      small-bowel obstructions, reoperations, carcinoma, and deaths. RESULTS: We
      reviewed 32 studies with 1616 patients who underwent 4538 strictureplasties. One
      thousand one hundred fifty-seven patients underwent conventional
      strictureplasties with an early complication rate of 15%; 459 patients underwent
      nonconventional strictureplasties with an early complication rate of 8%. A late
      complication rate of 29% for the conventional strictureplasty group and 17% for
      the nonconventional strictureplasty group was noted. LIMITATIONS: We are limited
      by the data published with the inherent risk of finding and analyzing mostly
      articles with positive results. CONCLUSION: The nonconventional strictureplasty
      techniques were noninferior to the conventional strictureplasty procedures with
      respect to all prespecified outcomes.

PMID- 22595859
TI  - High-yield synthesis of millimetre-long, semiconducting carbon nitride nanotubes
      with intense photoluminescence emission and reproducible photoconductivity.
AB  - High-yield synthesis of millimetre-long, semiconducting nanotubular g-C(3)N(4)
      with aspect ratio higher than 10,000 and strong photoluminscence emission was
      reported. The formation process of the nanotube was based on one-dimensional
      fibrous self-assembly of the protonated melamine in glycol mediated with nitric
      acid aqueous solution, which was subsequently thermalyzed into tubular carbon
      nitride through a rolling-up mechanism. The synthesized carbon nitride nanotube
      exhibits intense luminescent emission, fast photoresponse, and reproducible
      photoconductivity.

PMID- 22595860
TI  - Cloning, characterization, and expression analysis of a thioredoxin from orange
      spotted grouper (Epinephelus coioides).
AB  - Thioredoxins (TRXs) are a family of small, highly conserved proteins that are
      essential for the maintenance of cellular homeostasis. In this study, a
      thioredoxin gene was cloned from orange-spotted grouper, Epinephelus coioides
      (designated as Ec-TRX). The full-length cDNA of Ec-TRX was comprised of 767bp
      with a 327bp open reading frame that encodes a putative protein of 108 amino
      acids. Quantitative real-time PCR analysis revealed that the Ec-TRX mRNA was
      distributed abundantly in grouper, E. coioides skin and liver, and the expression
      in liver was up-regulated after viral challenge with Singapore grouper iridovirus
      (SGIV). Recombinant Ec-TRX (rEc-TRX) was expressed in Escherichia coli BL21 (DE3)
      and purified for mouse anti-Ec-TRX serum preparation. The rEc-TRX fusion protein
      was demonstrated to possess the expected redox activity in enzymatic analysis,
      and scavenge free radicals and protect supercoiled DNA from oxidative damage
      induced by a metal-ion catalyzed oxidation reaction. Subcellular localization
      revealed that Ec-TRX was distributed in both cytoplasm and nucleus.
      Overexpression of Ec-TRX in grouper spleen (GS) cells could promote the growth of
      GS cells and inhibit the replication of SGIV. These results suggest that Ec-TRX
      could function as an important antioxidant in a physiological context, and
      perhaps is involved in the responses to viral challenge.

PMID- 22595861
TI  - Proton transport in functionalised additives for PEM fuel cells: contributions
      from atomistic simulations.
AB  - The conventional polymer electrolyte membrane (PEM) materials for fuel cell
      applications strongly rely on temperature and pressure conditions for optimal
      performance. In order to expand the range of operating conditions of these
      conventional PEM materials, mesoporous functionalised SiO(2) additives are
      developed. It has been demonstrated that these additives themselves achieve
      proton conductivities approaching those of conventional materials. However, the
      proton conduction mechanisms and especially factors influencing charge carrier
      mobility under different hydration conditions are not well known and difficult to
      separate from concentration effects in experiments. This tutorial review
      highlights contributions of atomistic computer simulations to the basic
      understanding and eventual design of these materials. Some basic introduction to
      the theoretical and computational framework is provided to introduce the reader
      to the field, the techniques are in principle applicable to a wide range of other
      situations as well. Simulation results are directly compared to experimental data
      as far as possible.

PMID- 22595862
TI  - Renal and hepatic tumors in the neonatal period.
AB  - Renal and hepatic tumors in neonates are extremely rare. Nevertheless it is
      important for clinicians to be familiar with them. Both renal and hepatic
      neonatal tumors are heterogeneous collections of several tumor types. Some renal
      and hepatic tumors are benign and may require no interventions whereas others can
      be associated with significant morbidity and even mortality and may require
      multimodality treatment. Early diagnosis and initiation of the proper treatment
      plan is crucial for achieving the best outcomes for these rare tumors in this
      vulnerable population.

PMID- 22595863
TI  - Should we respect precedent autonomy in life-sustaining treatment decisions?
AB  - The recent judgement in the case of Re:M in which the Court held that it would be
      unlawful to withdraw artificial nutrition and hydration from a woman in a
      minimally conscious state raises a number of ethical issues of wide application.
      Central to these is the extent to which precedent autonomous decisions should be
      respected in the absence of a legally binding advance decision. Well-being
      interests can survive the loss of many of the psychological faculties that
      support personhood. A decision to respect precedent autonomy can contradict the
      well-being interests of the individual after capacity is lost. These decisions
      raise difficult questions about personal identity and about the threshold of
      evidence that is required of an earlier decision in order for it to be respected.

PMID- 22595864
TI  - Withdrawing and withholding artificial nutrition and hydration from patients in a
      minimally conscious state: re: M and its repercussions.
AB  - In 2011 the English Court of Protection ruled that it would be unlawful to
      withdraw artificial nutrition and hydration from a woman, M, who had been in a
      minimally conscious state for 8 years. It was reported as the first English legal
      case concerning withdrawal of artificial nutrition and hydration from a patient
      in a minimally conscious state who was otherwise stable. In the absence of a
      valid and applicable advance decision refusing treatment, of other life-limiting
      pathology or excessively burdensome suffering, the judgement makes it clear that
      the obligation on health professionals falls strongly in favour of preserving
      life. Although the Court sought to limit the judgement as closely as possible to
      the facts of the case, it is likely to have a significant impact on life
      sustaining treatment decisions for people in states of low awareness. This paper
      outlines the main legal features of the judgement. 

PMID- 22595865
TI  - Investigating clustering in interval-censored udder quarter infection times in
      dairy cows using a gamma frailty model.
AB  - Udder infections in dairy cows are observed at udder quarter level. Therefore,
      the best strategy to study infection dynamics of particular bacteria causing
      mastitis is to follow up and model individual udder quarter infection times.
      Udder quarter infection times, however, are not independent as they are clustered
      within a cow and herds. Another challenge in modelling infection times is that
      the exact infection time is unknown; it is only known that the infection has
      taken place in the interval between the last negative and the first positive
      sample. We applied a technique based on the gamma frailty model which handles the
      clustering and interval censoring simultaneously. Parameter estimates can be
      obtained analytically and their variance is obtained by the inverse of the
      hessian matrix. The proposed technique was applied to udder quarter infection
      times for Corynebacterium bovis, Staphylococcus aureus and Streptococcus uberis.
      Multiparous cows were more likely to get infected earlier in lactation with C.
      bovis or S. uberis than primiparous cows. The times to infection of all three
      bacteria were highly clustered at cow level and the results of a stratified model
      on a subset of herds suggested a high clustering on herd level for C. bovis and
      S. uberis.

PMID- 22595866
TI  - Fibers of reduced graphene oxide nanoribbons.
AB  - Reduced graphene oxide nanoribbon fibers were fabricated by using an
      electrophoretic self-assembly method without the use of any polymer or
      surfactant. We report electrical and field emission properties of the fibers as a
      function of reduction degree. In particular, the thermally annealed fiber showed
      superior field emission performance with a low potential for field emission (0.7
      V um(-1)) and a giant field emission current density (400 A cm(-2)). Moreover,
      the fiber maintains a high current level of 300 A cm(-2) corresponding to 1 mA
      during long-term operation.

PMID- 22595867
TI  - Reductant-directed formation of PS-PAMAM-supported gold nanoparticles for use as
      highly active and recyclable catalysts for the aerobic oxidation of alcohols and
      the homocoupling of phenylboronic acids.
AB  - Polystyrene-polyamidoamine-supported gold nanoparticles were prepared using a
      reductant-directed formation strategy. The resulting catalysts exhibited
      excellent activities in the aerobic oxidation of benzyl alcohols and the
      homocoupling of phenylboronic acids under mild conditions and can be recycled at
      least 14 times without significant loss of activity.

PMID- 22595868
TI  - Smaller volumes of caudate nuclei in prepubertal children with ADHD: impact of
      age.
AB  - OBJECTIVE: Age-related abnormalities in caudate volumes have been reported to
      differ across the periods of childhood and puberty in children with ADHD. This
      study assessed caudate volumetric abnormalities across two narrow age clusters
      within the childhood period. METHOD: Three-dimensional manual tracings of the
      head and body of the caudate nucleus and of the cerebrum were acquired from 26
      medication-naive boys with a diagnosis of ADHD (ages 5.9-10.8 years), and 24 age
      matched normal controls. RESULTS: Boys with ADHD had smaller total caudate
      volumes relative to controls, F(1,48)=4.29, p=0.04. Adjustment of caudate volumes
      with respect to age demonstrated that this group difference was driven solely by
      participants in the 5.9-7.3 year range, F(1, 46)=5.64, p=0.022, with an effect
      size of d=0.69. No Group effect was found in older participants, F(1, 46)=0.82,
      p=0.37. CONCLUSIONS: These novel findings suggest a different pattern of caudate
      volume abnormalities across narrow age clusters prior to puberty in boys with
      ADHD. Anatomical differences in brain structures related to ADHD in prepubertal
      children should be evaluated with respect to the changing developmental
      trajectory of brain regions within this period of rapid brain growth.

PMID- 22595869
TI  - Negative expectancies in posttraumatic stress disorder: neurophysiological (N400)
      and behavioral evidence.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) is a disorder that theoretically
      and clinically is thought to be associated with persistent and exaggerated
      negative expectancies. This study used the N400 event-related potential (ERP) to
      investigate expectancies for threatening endings to ambiguous sentence stems. The
      N400 ERP is thought to reflect the amount of effort required to integrate a
      stimulus into a given context. In sentence reading tasks, the N400 is reliably
      larger when a word is unexpected. METHOD: In this study, fifty-seven trauma
      survivors of various types (22 with PTSD and 35 without) read ambiguous sentence
      stems on a computer screen. These sentence stems were completed with either an
      expected ("The unfortunate man lost his...wallet"), unexpected ("The unfortunate
      man lost his...artist"), or threatening word endings ("The unfortunate man lost
      his...leg"). RESULTS: Participants with PTSD, as compared to those without,
      showed significantly smaller N400s to threatening sentence endings suggesting
      enhanced expectancies for threat. Behavioral responses supported this conclusion.
      CONCLUSIONS: These findings are consistent with the clinical presentation of
      hypervigilance and proposed revisions to the DSM-V that emphasize persistent and
      exaggerated negative expectations about one's self, others, or the world.
      Relative to earlier behavioral studies, this work further suggests that this
      expectancy bias occurs automatically and at the early stages of information
      processing. The discussion focuses on the potential impact of a negative
      expectancy bias in PTSD and the value of the ambiguous sentence paradigm for
      studying PTSD as well as other disorders.

PMID- 22595870
TI  - Alcohol and cannabis use and mortality in people with schizophrenia and related
      psychotic disorders.
AB  - The impact of co-morbid substance use on mortality is not well studied in
      psychotic disorders. The objective of this study was to examine the impact of
      substance use on mortality in people with psychotic disorders and alcohol and/or
      drug use. We examined the rate of substance use and the risk of substance use on
      mortality risk over a 4-10 year period in 762 people with psychotic disorders.
      Deceased patients were identified from the Social Security Death Index and the
      Maryland Division of Vital Records. Substance use was defined as regular and
      heavy use or abuse or dependence. Seventy seven percent had co-morbid lifetime
      substance use, with co-morbid cannabis and alcohol use occurring most commonly.
      Out of 762 subjects, 62 died during follow up. In a Cox model, predicted
      mortality risk was higher in age group 35-55 compared to <35 years and in males,
      but reduced in cannabis users. Overall five- (3.1% vs 7.5%) and ten-year
      mortality risk (5.5% vs. 13.6%) was lower in cannabis users than in non-users
      with psychotic disorders (p = 0.005) in a survival model. Alcohol use was not
      predictive of mortality. We observed a lower mortality risk in cannabis-using
      psychotic disorder patients compared to cannabis non-users despite subjects
      having similar symptoms and treatments. Future research is warranted to replicate
      these findings and to shed light on the anti-inflammatory properties of the
      endocannabinoid system and its role in decreased mortality in people with
      psychotic disorders.

PMID- 22595871
TI  - Region-specific glutamate changes in patients with unipolar depression.
AB  - The present study aimed to investigate glutamate concentrations in patients with
      unipolar depression in the midcingulate cortex (MCC) as compared to the left
      dorsolateral prefrontal cortex (DLPFC). We hypothesized a dissociation of
      glutamate levels with unchanged levels in DLPFC and abnormally changed levels in
      MCC as well as differential effects of antidepressant pharmacotherapy. Glutamate
      was determined using magnetic resonance spectroscopy at 3 T in DLPFC and MCC in
      fourteen depressed patients and matched healthy volunteers. A follow-up
      measurement was performed after 4 weeks of antidepressant treatment. The main
      finding is a region-specific pattern of glutamate concentrations with increased
      MCC glutamate concentrations and no significant differences in DLPFC glutamate
      concentrations in unipolar depressive patients compared to healthy controls.
      Response and non-response to antidepressant pharmacotherapy were predicted by
      high glutamate at baseline in DLPFC and MCC, respectively. In addition, treatment
      responders showed a further increase in DLPFC glutamate levels after successful
      antidepressant treatment. Findings indicate altered region-specific glutamate
      concentrations in DLPFC and MCC that are predictive of response and non-response,
      respectively, to antidepressant pharmacotherapy. These findings might serve as a
      starting point for future studies in which the value of this metabolite pattern
      for treatment response prediction should be investigated.

PMID- 22595872
TI  - Willingness of Kenyan HIV-1 serodiscordant couples to use antiretroviral-based
      HIV-1 prevention strategies.
AB  - INTRODUCTION: Antiretroviral treatment (ART) and pre-exposure prophylaxis (PrEP)
      have demonstrated efficacy as new human immunodeficiency virus-1 (HIV-1)
      prevention approaches for HIV-1 serodiscordant couples. METHODS: Among Kenyan HIV
      1 serodiscordant heterosexual couples participating in a clinical trial of PrEP,
      we conducted a cross-sectional study and used descriptive statistical methods to
      explore couples' willingness to use antiretrovirals for HIV-1 prevention. The
      study was conducted before July 2011, when studies among heterosexual populations
      reported that ART and PrEP reduced HIV-1 risk. RESULTS: For 181 couples in which
      the HIV-1-infected partner had a CD4 count >=350 cells per microliter and had not
      yet initiated ART (and thus did not qualify for ART under Kenyan guidelines),
      60.2% of HIV-1 infected partners (69.4% of men and 57.9% of women) were willing
      to use early ART (at CD4 >=350 cells per microliter) for HIV-1 prevention. Among
      HIV-1 uninfected partners, 92.7% (93.8% of men and 86.1% of women) reported
      willingness to use PrEP. When given a hypothetical choice of early ART or PrEP
      for HIV-1 prevention, 52.5% of HIV-1-infected participants would prefer to
      initiate ART early and 56.9% of HIV-1-uninfected participants would prefer to use
      PrEP. CONCLUSIONS: Nearly 40% of Kenyan HIV-1-infected individuals in known HIV-1
      serodiscordant partnerships reported reservations about early ART initiation for
      HIV-1 prevention. PrEP interest in this PrEP-experienced population was high.
      Strategies to achieve high uptake and sustained adherence to ART and PrEP for HIV
      1 prevention in HIV-1 serodiscordant couples will require responding to couples'
      preferences for prevention strategies.

PMID- 22595873
TI  - Racial/Ethnic disparities in ART adherence in the United States: findings from
      the MACH14 study.
AB  - BACKGROUND: Minority race/ethnicity is generally associated with antiretroviral
      therapy nonadherence in US-based studies. Limitations of the existing literature
      include small samples, subjective adherence measures, and inadequate control for
      potential confounders such as mental health and substance use, which have been
      consistently associated with poorer adherence. METHODS: Individual-level data
      were pooled from 13 US-based studies employing electronic drug monitoring to
      assess adherence. Adherence was operationalized as percent of prescribed doses
      taken from the first 12 (monthly) waves of data in each study. Depression
      symptoms were aggregated from several widely used assessments, and substance use
      was operationalized as any use of cocaine/stimulants, heroin/opiates, ecstasy,
      hallucinogens, or sedatives in the 30-365 days preceding baseline. RESULTS: The
      final analytic sample of 1809 participants ranged in age from 18 to 72 years and
      was 67% male. Participants were 53% African American, 14% Latino, and 34% White.
      In a logistic regression adjusting for age, gender, income, education, and site,
      race/ethnicity was significantly associated with adherence (P < 0.001) and
      persisted in a model that also controlled for depression and substance use (P <
      0.001), with African Americans having significantly lower adherence than Latinos
      [odds ratio (OR) = 0.72, P = 0.04] and whites (OR = 0.60, P < 0.001). Adherence
      did not differ between whites and Latinos (OR = 0.84, P = 0.27). CONCLUSIONS:
      Racial/ethnic differences in demographics, depression, and substance abuse do not
      explain the lower level of antiretroviral therapy adherence in African Americans
      observed in our sample. Further research is needed to explain the persistent
      disparity and might examine factors such as mistrust of providers, health
      literacy, and inequities in the health care system.

PMID- 22595875
TI  - Whole-genome bisulfite DNA sequencing of a DNMT3B mutant patient.
AB  - The immunodeficiency, centromere instability and facial anomalies (ICF) syndrome
      is associated to mutations of the DNA methyl-transferase DNMT3B, resulting in a
      reduction of enzyme activity. Aberrant expression of immune system genes and
      hypomethylation of pericentromeric regions accompanied by chromosomal instability
      were determined as alterations driving the disease phenotype. However, so far
      only technologies capable to analyze single loci were applied to determine
      epigenetic alterations in ICF patients. In the current study, we performed whole
      genome bisulphite sequencing to assess alteration in DNA methylation at base pair
      resolution. Genome-wide we detected a decrease of methylation level of 42%, with
      the most profound changes occurring in inactive heterochromatic regions,
      satellite repeats and transposons. Interestingly, transcriptional active loci and
      ribosomal RNA repeats escaped global hypomethylation. Despite a genome-wide loss
      of DNA methylation the epigenetic landscape and crucial regulatory structures
      were conserved. Remarkably, we revealed a mislocated activity of mutant DNMT3B to
      H3K4me1 loci resulting in hypermethylation of active promoters. Functionally, we
      could associate alterations in promoter methylation with the ICF syndrome
      immunodeficient phenotype by detecting changes in genes related to the B-cell
      receptor mediated maturation pathway.

PMID- 22595876
TI  - A genomic reservoir for Tnfrsf genes is developmentally regulated and imprinted
      in the mouse.
AB  - Tumor necrosis factor receptor superfamily is composed of at least 26 members in
      the mouse, three of which exist as a cluster within the imprinted Kcnq1 domain on
      chromosome 7. Tnfrsf22,  23 and  26 contain typical cystein-rich domains and
      Tnfrsf22 and  23 can bind ligands but have no signaling capacity. Thus, they are
      assumed to be decoy receptors. The developmental expression profile of these
      genes is unknown and knowledge of their imprinting patterns is incomplete and
      controversial. We found that all three genes are expressed during mouse embryonic
      development, and that they have a strong maternal bias, indicating that they may
      be affected by the KvDMR, the Kcnq1 imprinting control region. We found
      expression of an antisense non-coding RNA, AK155734, in embryos and some neonatal
      tissues. This RNA overlaps the Tnfrsf22 and possibly the Tnfrsf23 coding regions
      and is also expressed with a maternal bias. We were interested in exploring the
      evolutionary origins of the three Tnfrsf genes, because they are absent in the
      orthologous human Kcnq1 domain. To determine whether the genes were deleted from
      humans or acquired in the rodent lineage, we performed phylogenetic analyses. Our
      data suggest that TNFRSF sequences were duplicated and/or degenerated or
      eliminated from the KCNQ1 region several times during the evolution of mammals.
      In humans, multiple mutations (point mutations and/or deletions) have accumulated
      on the ancestral TNFRSF, leaving a single short non-functional sequence.

PMID- 22595877
TI  - Human cytomegalovirus infection is sensitive to the host cell DNA methylation
      state and alters global DNA methylation capacity.
AB  - Human Cytomegalovirus (HCMV) is a ubiquitous herpesvirus that infects and
      establishes latency in the majority of the human population and may cause fatal
      infections in immunocompromised patients. Recent data implies a close interaction
      between HCMV encoded proteins and cellular epigenetic mechanisms such as histone
      acetylation and deacetylation. In this study, we investigated the interactions
      between HCMV infection and the DNA methylation machinery in different host cells
      using several approaches. We found that colon cancer cell line HCT-116 lacking
      the DNMT1 and DNMT3b methyltransferases was susceptible to HCMV-AD169 infection,
      while wild-type cells were non-susceptible. Treatment of wild-type HCT-116 cells
      with 5-azacytidine rendered them susceptible to infection. Further investigation
      of HCMV infected MRC-5 fibroblasts demonstrated significant global
      hypomethylation, a phenomenon that was virus strain-specific and associated with
      the re-localization of DNMT1 and DNMT3b from the nucleus to the cytoplasm. The
      cytoplasmic accumulation of DNMT1 was also evident in in vitro infected
      macrophages and in epithelial cells in tissue samples from patients with
      inflammatory bowel disease and concomitant HCMV infection. Foscavir treatment of
      virus infected fibroblasts did not affect the majority of the virus induced
      nuclear exclusion of DNMT1, which suggest that it is dependent on viral IE gene
      products. In conclusion, HCMV infection results in profound effects on the host
      cell DNA methylation machinery and is associated with inflammation in vivo. Our
      results improve the understanding of cytomegalovirus pathogenesis and open the
      search for new antiviral therapy targets. These findings may also contribute to
      the further understanding of mechanisms involved in DNA methylation abnormalities
      in physiological and pathological conditions.

PMID- 22595881
TI  - Rate-limiting mechanisms in high-temperature growth of catalyst-free InAs
      nanowires with large thermal stability.
AB  - We identify the entire growth parameter space and rate-limiting mechanisms in non
      catalytic InAs nanowires (NWs) grown by molecular beam epitaxy. Surprisingly huge
      growth temperature ranges are found with maximum temperatures close to ~600
      degrees C upon dramatic increase of V/III ratio, exceeding by far the typical
      growth temperature range for catalyst-assisted InAs NWs. Based on quantitative in
      situ line-of-sight quadrupole mass spectrometry, we determine the rate-limiting
      factors in high-temperature InAs NW growth by directly monitoring the critical
      desorption and thermal decomposition processes of InAs NWs. Both under dynamic
      (growth) and static (no growth, ultra-high vacuum) conditions the (111)-oriented
      InAs NWs evidence excellent thermal stability at elevated temperatures even under
      negligible supersaturation. The rate-limiting factor for InAs NW growth is hence
      dominated by In desorption from the substrate surface. Closer investigation of
      the group-III and group-V flux dependences on growth rate reveals two apparent
      growth regimes, an As-rich and an In-rich regime defined by the effective As/In
      flux ratio, and maximum achievable growth rates of > 6 um h(-1). The unique
      features of high-T growth and excellent thermal stability provide the opportunity
      for operation of InAs-based NW materials under caustic environment and further
      allow access to temperature regimes suitable for alloying non-catalytic InAs NWs
      with GaAs.

PMID- 22595882
TI  - Copper-induced N-N bond cleavage results in an octanuclear expanded-core grid
      like complex.
AB  - Reaction of copper(I) acetate and 4-amino-3,5-di(2-pyridyl)-1,2,4-triazole (adpt)
      in methanol under ambient conditions yields octanuclear
      [Cu(II)(8)(dpt)(4)(OH)(4)(OAc)(8)]; OAc = acetate anion, and dpt(-) = anion of
      deaminated adpt, 3,5-di(2-pyridyl)-1,2,4-triazolate. However, reaction of
      copper(ii) acetate with dptH gives tetranuclear
      [Cu(II)(4)(dpt)(2)(OH)(OMe)(OAc)(4)].

PMID- 22595883
TI  - Observation of divergent isotope effects as well as metal ion-modulated T(C) and
      spin-canting nature in isostructural supramolecular magnets.
AB  - The ion-pair complexes of [4-NH(2)-PyH][M(mnt)(2)] (M = Pt for 1 and Ni for 3)
      and their deuterated analogues [4-NH(2)-PyD][M(mnt)(2)] (M = Pt for 2 and Ni for
      4) are isostructural with each other. Four complexes crystalline in monoclinic
      space group C2/c, whose asymmetric unit consists of two halves of [M(mnt)(2)](-)
      anions and one cation, show quite similar cell parameters and almost identical
      packing structures as well. In the crystals of 1-4, two types of
      crystallographically inequivalent [M(mnt)(2)](-) anions construct individual
      layers, which are separated by the cation layer; the supramolecular networks are
      formed via the H-bonding interactions between the [M(mnt)(2)](-) and 4-NH(2)
      PyH(+) (or 4-NH(2)-PyD(+)) ions as well as the weakly pipi stacking interactions
      between the [M(mnt)(2)](-) anions. The four isostructural complexes exhibit
      canted antiferromagnetism, arising from the non-collinearity of the magnetic
      moments between the crystallographically inequivalent anion layers, with T(C) ~
      14.8 K for 1, 13.6 K for 2, 7.7 K for 3 and 8.8 K for 4, respectively. Ac
      magnetic susceptibility measurements revealed that 1 and 2 show spin canting,
      while 3 and 4 show hidden-spin canting characteristics. The isostructural 1 and 3
      were deuterated to give the divergent isotope effects on the cell volume and
      T(C).

PMID- 22595884
TI  - Silver(I)-catalyzed carboxylation of arylboronic esters with CO2.
AB  - A variety of arylboronic esters were efficiently carboxylated with CO(2) using a
      simple AgOAc/PPh(3) catalyst, affording the corresponding carboxylic acids in
      good yield. This simple and efficient silver(i) catalytic system showed wide
      functional group compatibility.

PMID- 22595886
TI  - Elevation of transcription factor Islet-1 levels in vivo increases beta-cell
      function but not beta-cell mass.
AB  - A decrease in the expression of Islet-1 (Isl-1), an islet transcription factor,
      has been reported in several physiological settings of reduced beta-cell
      function. Here, we investigate whether an increased level of Isl-1 in islet cells
      can enhance beta-cell function and/or mass. We demonstrate that transgenic mice
      with Isl-1 overexpression display improved glucose tolerance and enhanced insulin
      secretion without significant changes in beta cell mass. From our microarray
      study, we identify approximately 135 differentially expressed genes in the islets
      of Isl-1 overexpressing mice that have been implicated to function in numerous
      biological processes including protein trafficking, metabolism and
      differentiation. Using real-time PCR we have confirmed upregulation of Caps2,
      Sec14l4, Slc2a10, P2rx7, Afamin, and Neurogenin 3 that may in part mediate the
      observed improved insulin secretion in Isl-1 overexpressing mice. These findings
      show for the first time that Isl-1 is a key factor in regulating adult beta cell
      function in vivo, and suggest that Isl-1 elevation could be beneficial to improve
      glucose homeostasis.

PMID- 22595887
TI  - Site-specific stamping of graphene micro-patterns over large areas using flexible
      stamps.
AB  - Site-specific stamping has the potential of becoming a low-cost, high-throughput
      method for depositing specific-shaped graphene micro-patterns over large areas on
      a wide variety of substrates. The use of an approach involving flexible stamps
      presented here represents an important advance towards reaching that potential.
      This approach entails lithographic creation (dry etching) of high-quality micro
      pillar arrays of highly oriented pyrolytic graphite (HOPG) over large areas. This
      is followed by embedding the micro-pillar arrays in polydimethylsiloxane (PDMS),
      and detaching them from the HOPG base. This results in flexible stamps containing
      embedded HOPG micro-pillar arrays with freshly cleaved stamping surfaces. The
      flexible HOPG/PDMS stamps are then brought into contact with substrate surfaces
      to site-specifically stamp graphene or few-layer graphene (FLG) arrays over large
      areas. The freshly cleaved nature of the micro-pillar surfaces in the flexible
      stamps, the low elastic modulus of the flexible stamps and the elimination of
      sidewall deposits on the micro-pillars allow for more uniform stamping, relative
      to the use of stiff HOPG stamps from earlier studies. This approach has the
      potential to expand the substrate choice for graphene or FLG stamping to include
      curved and/or flexible substrates that could have an impact on the burgeoning
      field of flexible/stretchable electronics.

PMID- 22595891
TI  - Theoretical study on the influence of ancillary and cyclometalated ligands on the
      electronic structures and optoelectronic properties of heteroleptic iridium(III)
      complexes.
AB  - We report a theoretical analysis of a series of heteroleptic iridium(III)
      complexes (dox)(2)Ir(acac) [dox = 2,5-diphenyl-1,3,4-oxadiazolato-N,C(2), acac =
      acetylacetonate] (1a), (fox)(2)Ir(acac) [fox = 2,5-bis(4-fluorophenyl)-1,3,4
      oxadiazolato-N,C(2)] (1b), (fox)(2)Ir(Et(2)dtc) [Et(2)dtc = N,N'
      diethyldithiocarbamate] (2), (fox)(2)Ir(Et(2)dtp) [Et(2)dtp = O,O'
      diethyldithiophosphate] (3), (pypz)(2)Ir(acac) [pypz = 3,5-di(2-pyridyl)pyrazole]
      (4a), (O-pypz)(2)Ir(acac) (4b), (S-pypz)(2)Ir(acac) (4c) and (bptz)(2)Ir(acac)
      [bptz = 3-tert-butyl-5-(2-pyridyl)triazole] (5) by using the density functional
      theory (DFT) method to investigate their electronic structures and photophysical
      properties and obtain further insights into the phosphorescent efficiency
      mechanism. Meanwhile, we also investigate the influence of ancillary and
      cyclometalated ligands on the properties of the above complexes. The results
      reveal that the nature of the ancillary ligands can influence the electron
      density distributions of frontier molecular orbitals and their energies,
      resulting in change in transition character and emission color, while the
      different cyclometalated ligands have a large impact on the charge transfer
      performances of the studied complexes. The calculated absorption and luminescence
      properties of the four complexes 1a, 1b, 2 and 3 are compared with the available
      experimental data and a good agreement is obtained. Further, the assumed
      complexes 4a and 4b possess better charge transfer abilities and more balanced
      charge transfer rates, and they are potential candidates as blue-emitting
      materials.

PMID- 22595889
TI  - Cancer chromosomal instability: therapeutic and diagnostic challenges.
AB  - Chromosomal instability (CIN)-which is a high rate of loss or gain of whole or
      parts of chromosomes-is a characteristic of most human cancers and a cause of
      tumour aneuploidy and intra-tumour heterogeneity. CIN is associated with poor
      patient outcome and drug resistance, which could be mediated by evolutionary
      adaptation fostered by intra-tumour heterogeneity. In this review, we discuss the
      clinical consequences of CIN and the challenges inherent to its measurement in
      tumour specimens. The relationship between CIN and prognosis supports assessment
      of CIN status in the clinical setting and suggests that stratifying tumours
      according to levels of CIN could facilitate clinical risk assessment.

PMID- 22595892
TI  - Cardiac rehabilitation participant with sickle cell trait and statin-related
      hepatotoxicity: a case report.
AB  - PURPOSE: Exercise recommendations for patients with sickle cell trait (SCT) and
      myocardial infarction (MI) are limited. This case report describes such a
      patient, who subsequently participated in cardiac rehabilitation (CR). CASE:
      Patient experienced sudden intense chest pressure and shortness of breath while
      singing in church. Electrocardiogram and cardiac enzymes confirmed acute ST
      elevation MI. Laboratory tests indicated hyperlipidemia and elevated liver enzyme
      levels >4 times the upper normal limit (UNL). Day 40 post-MI, the patient
      returned to the hospital complaining of daily chest discomfort, atypical for
      angina pectoris. Following an unremarkable stress test result, the patient was
      encouraged to proceed with CR. Patient made regular progress through CR, although
      continued to experience paroxysmal chest discomfort away from CR, which he denied
      having during exercise. On day 75, his lipid profile met recommended targets
      while taking atorvastatin, but with liver enzymes >38 times UNL. Atorvastatin was
      discontinued at day 85, to which his enzymes responded appropriately, but by day
      165, hyperlipidemia had returned. Rosuvastatin was started but was discontinued
      (day 197), with liver enzymes 6 times UNL. He continued CR without lipid therapy
      but at CR completion, the lipid panel did not meet targets. However, fitness and
      social indices improved significantly, although he occasionally still experienced
      chest pain, but with lesser frequency and intensity, and never with exercise.
      CONCLUSIONS: CR in a patient with SCT, MI, and statin-related hepatotoxicity
      requires several specific considerations. Although SCT-exercise associated deaths
      are described in the literature, this case suggests that such patients can
      benefit from CR and can exercise safely.

PMID- 22595893
TI  - Variation in patient perceptions of healthcare provider endorsement of cardiac
      rehabilitation.
AB  - PURPOSE: Cardiac rehabilitation (CR) is significantly underutilized. However,
      physician endorsement promotes greater patient utilization. This study examined
      perceptions of provider endorsement by patients (1) of sociodemographic groups
      who are often less represented in CR and by clinical indication and (2) by type
      of healthcare provider and place of referral. METHODS: Referred cardiac (N =
      1156) inpatients from 11 hospitals across Ontario completed a sociodemographic
      survey inhospital and a mailed followup survey 1 year later. Respondents self
      reported perceived healthcare provider endorsement of CR on a 5-point Likert
      scale, type of referring healthcare provider, and where the referral was
      initiated. RESULTS: The overall perceived strength of healthcare provider
      endorsement to CR was 3.75 +/- 1.15. Patients who perceived greater endorsement
      were significantly more likely to enrol (OR = 2.07) and attend a greater
      percentage of CR sessions (P < .001). Student t tests showed that women (P <
      .01), those older than 65 years (P < .01), with lower annual family income (P <
      .001), less than high school education (P < .01), who were retired (P < .01), or
      had lower subjective social status (P < .01) reported significantly lower
      perceived healthcare provider endorsement of CR than their respective
      counterparts. Perception of CR endorsement did not differ significantly on the
      basis of location of referral initiation (P >= .05), but those who discussed CR
      with family doctors (P < .05), cardiologists (P < .05), or cardiac surgeons (P <
      .01) reported significantly greater endorsement than those discussing CR with
      nurses. CONCLUSIONS: Given the proven benefits of CR, all healthcare providers
      are recommended to universally and strongly encourage CR participation among
      their patients in order to optimize utilization and subsequent recovery.

PMID- 22595894
TI  - Comparison of walking with poles and traditional walking for peripheral arterial
      disease rehabilitation.
AB  - PURPOSE: The purpose of this study was to compare the effects of a 24-week
      walking with poles rehabilitation program with a traditional 24-week walking
      program on physical function in patients with peripheral arterial disease (PAD).
      METHODS: Patients with PAD (n = 103, age = 69.7 +/- 8.9 years, ankle-brachial
      index < 0.90 or evidence of calcified vessels) were randomized into a
      rehabilitation program of traditional walking (n = 52) or walking with poles (n =
      51). Patients exercised 3 times per week for 24 weeks. Exercise endurance was
      measured by time walked on a constant work rate treadmill test at 6, 12, and 24
      weeks. Perceived physical function was measured by the Medical Outcomes Study
      Short Form-36 and Walking Impairment Questionnaire. Tissue oxygenation was
      measured using near-infrared spectroscopy. RESULTS: Patients assigned to the
      traditional walking group walked longer at 24 weeks than those assigned to the
      pole walking group (21.10 +/- 17.07 minutes and 15.02 +/- 12.32 minutes,
      respectively, P = .037). There were no differences between the groups in tissue
      oxygenation. However, there was a significant lengthening of time for which it
      took to reach minimum tissue oxygenation values (P < .001) within the groups on
      the constant work rate test. There were no differences between the groups in
      perceived physical function as measured by the Physical Function subscale on the
      Medical Outcomes Study Short Form-36 or perceived walking distance as measured by
      the Walking Distance subscale on the Walking Impairment Scale. CONCLUSIONS:
      Traditional walking was superior to walking with poles in increasing walking
      endurance on a constant work rate treadmill test for patients with PAD.

PMID- 22595896
TI  - Rapid microwave-assisted synthesis of hierarchical ZnO hollow spheres and their
      application in Cr(VI) removal.
AB  - A rapid one-pot synthesis of hierarchical ZnO hollow spheres consisting of
      nanoparticles was realized by a facile microwave-assisted solvothermal method
      using ethanol as the solvent. According to the time-dependent observation of the
      formation process, a tentative mechanism based on ethyl acetate bubble-templating
      self-assembly of ZnO nanoparticles was proposed for the formation of the ZnO
      hollow spheres. Compared with the conventional heating, the microwave irradiation
      resulted in a significantly shortened reaction time (within 30 min) and
      considerably improved quality of the ZnO hollow spheres, such as narrower size
      distribution and more regular morphology, owing to the high heating rate and thus
      the accelerated reaction rate. It was shown that the microwave-assisted synthesis
      of ZnO nanostructures with tunable morphologies can be realized by judicious
      selection of appropriate solvents. The obtained ZnO hollow spheres exhibited an
      excellent adsorption capacity towards Cr(VI) ions in water because of their high
      surface area for adsorption and a good ability to preserve the accessible
      surface.

PMID- 22595897
TI  - Development of a near-infrared fluorescent probe for imaging of endogenous Cu+ in
      live cells.
AB  - We have constructed a novel NIR fluorescent turn-on Cu(+) probe suitable for
      imaging endogenous Cu(+) ions in living cells based on a tricarbocyanine scaffold
      and a high affinity Cu(+) receptor.

PMID- 22595898
TI  - Effect of cilostazol in preventing restenosis after carotid artery stenting using
      the carotid wallstent: a multicenter retrospective study.
AB  - BACKGROUND AND PURPOSE: Restenosis after CAS is a postoperative problem, with a
      reported frequency of approximately 2%-8%. However differences in stent design,
      procedure, and the antiplatelet agent appear to affect the incidence of
      restenosis. We assessed the frequency of restenosis and the effect of the
      antiplatelet agent CLZ in preventing restenosis after CAS by the standard
      procedure using the CWS. MATERIALS AND METHODS: Between May 2010 and October
      2011, 62 lesions in 60 consecutive patients underwent CAS using the CWS at 4
      medical institutions, and all patients were followed clinically and assessed by
      sonography, 3D-CTA, or angiography at 3 and 6 months postoperatively. Restenosis
      was defined as >=50% stenosis. The incidence of restenosis and the variation in
      the incidence of restenosis by the difference in type of antiplatelet agent
      between the CLZ group (n = 30; aspirin, 100 mg, and CLZ, 200 mg) and the non-CLZ
      group (n = 32; aspirin, 100 mg, and clopidogrel, 75 mg [n = 29]; or ticlopidine,
      100 mg [n = 2] or 200 mg [n = 1]) were retrospectively investigated. Two
      antiplatelet agents were given starting 1 week preoperatively until at least 3
      months postoperatively. RESULTS: Restenosis occurred in 5 patients (8.3%), but
      all were cases of asymptomatic lesions in the follow-up period. All 5 patients
      with restenosis were in the non-CLZ group, with no cases of restenosis in the CLZ
      group; the difference was significant (P = .0239). CONCLUSIONS: The restenosis
      rate after CAS by using the CWS was 8.3%. CLZ was associated with significant
      inhibition of restenosis.

PMID- 22595899
TI  - Inherited cerebellar ataxia in childhood: a pattern-recognition approach using
      brain MRI.
AB  - Ataxia is the principal symptom of many common neurologic diseases in childhood.
      Ataxias caused by dysfunction of the cerebellum occur in acute, intermittent, and
      progressive disorders. Most of the chronic progressive processes are secondary to
      degenerative and metabolic diseases. In addition, congenital malformation of the
      midbrain and hindbrain can also be present, with posterior fossa symptoms related
      to ataxia. Brain MR imaging is the most accurate imaging technique to investigate
      these patients, and imaging abnormalities include size, shape, and/or signal of
      the brain stem and/or cerebellum. Supratentorial and cord lesions are also
      common. This review will discuss a pattern-recognition approach to inherited
      cerebellar ataxia in childhood. The purpose is to provide a comprehensive
      discussion that ultimately could help neuroradiologists better manage this
      important topic in pediatric neurology.

PMID- 22595901
TI  - Apples.

PMID- 22595900
TI  - Therapeutic hypothermia for neonatal encephalopathy results in improved
      microstructure and metabolism in the deep gray nuclei.
AB  - BACKGROUND AND PURPOSE: Therapeutic hypothermia has reduced morbidity and
      mortality and is associated with a lower burden of lesions on conventional
      imaging in NE. However, its effects on brain microstructure and metabolism have
      not been fully characterized. We hypothesized that therapeutic hypothermia
      improves measures of brain microstructure and metabolism. MATERIALS AND METHODS:
      Forty-one neonates with moderate/severe NE (29 treated with hypothermia, 12
      nontreated) and 12 healthy neonates underwent MR imaging, DTI, and (1)H-MR
      spectroscopy. MR imaging scans were scored by the predominant pattern of brain
      injury: normal, watershed, and BG/thalamus. ADC, FA, Lac:NAA, and NAA:Cho values
      from bilateral BG and thalamus ROIs were averaged. T test and linear regression
      analysis were used to determine the association between hypothermia and MR
      imaging quantitative measures. RESULTS: Conventional MR imaging findings were
      normal in 41% of treated neonates; all nontreated neonates had brain injury.
      Values of MR imaging metrics were closer to normal in treated neonates compared
      with nontreated neonates: ADC was 63% higher in the BG and 116% higher in the
      thalamus (both P < .05), and Lac:NAA was 76% lower (P = .04) in the BG. Treated
      neonates with normal MR imaging findings had normal (1)H-MR spectroscopy
      metabolites, and ADC was higher by 35% in the thalamus (P = .03) compared with
      healthy neonates. CONCLUSIONS: Therapeutic hypothermia may reduce disturbances of
      brain metabolism and preserve its microstructure in the setting of NE, possibly
      by minimizing cytotoxic edema and cell death. Long-term follow-up studies are
      required to determine whether early post-treatment DTI and (1)H-MR spectroscopy
      will be useful biomarkers of treatment response.

PMID- 22595902
TI  - Clinical standardized fMRI reveals altered language lateralization in patients
      with brain tumor.
AB  - BACKGROUND AND PURPOSE: Brain tumors affecting language-relevant areas may
      influence language lateralization. The purpose of this study was to
      systematically investigate language lateralization in brain tumor patients using
      clinical language fMRI, comparing the results with a group of healthy volunteers.
      MATERIALS AND METHODS: Fifty-seven strictly right-handed patients with left
      hemispheric-space intracranial masses (mainly neoplastic) affecting either the
      Broca area (n = 19) or Wernicke area (n = 38) were prospectively enrolled in this
      study. Fourteen healthy volunteers served as a control group. Standardized
      clinical language fMRI, using visually triggered sentence- and word-generation
      paradigms, was performed on a 1.5T MR scanner. Semiautomated analyses of all
      functional data were conducted on an individual basis using BrainVoyager. A
      regional lateralization index was calculated for Broca and Wernicke areas
      separately versus their corresponding right-hemisphere homologs. RESULTS: In
      masses affecting the Broca area, a significant decrease in the lateralization
      index was found when performing word generation (P = .0017), whereas when
      applying sentence generation, the decrease did not reach statistical significance
      (P = .851). Masses affecting the Wernicke area induced a significant decrease of
      the lateralization index when performing sentence generation (P = .0007), whereas
      when applying word generation, the decrease was not statistically significant (P
      = .310). CONCLUSIONS: Clinical language fMRI was feasible for patients with brain
      tumors and provided relevant presurgical information by localizing essential
      language areas and determining language dominance. A significant effect of the
      brain masses on language lateralization was observed, with a shift toward the
      contralesional, nondominant hemisphere. This may reflect compensatory mechanisms
      of the brain to maintain communicative abilities.

PMID- 22595903
TI  - MR imaging of congenital or developmental neuropathic strabismus: common and
      uncommon findings.
AB  - BACKGROUND AND PURPOSE: High-resolution MR imaging enables direct imaging of the
      ocular motor nerves. The aim of this study was to assess the various causes of
      congenital or developmental neuropathic strabismus by using high-resolution MR
      imaging. MATERIALS AND METHODS: High-resolution MR imaging was performed to
      evaluate the ocular motor nerves (CNIII, CNIV, CNVI) in 247 consecutive patients
      with suspected congenital or developmental neuropathic strabismus. These MR
      images, along with those obtained from conventional MR imaging of the brain and
      the orbit, were evaluated. RESULTS: MR imaging abnormalities were found in 112
      patients: ocular motor nerve abnormalities in 98 patients (88%), orbital
      abnormalities in 9 patients (8%), and brain abnormalities in 5 patients (4%).
      Ocular motor nerve abnormalities were CNIV aplasia (63%), CNVI aplasia or
      hypoplasia (21%), CNIII aplasia or hypoplasia (3%), and combined CNIII aplasia
      and CNVI hypoplasia (1%). Orbital abnormalities were EOM hypoplasia (7%), EOM
      hypertrophy (1%), and fibrotic mass (1%). Brain abnormalities were
      periventricular leukomalacia (4%) and periventricular heterotopia (1%).
      CONCLUSIONS: Various MR imaging abnormalities were associated with congenital and
      developmental neuropathic strabismus. The most common abnormality was CNIV
      aplasia.

PMID- 22595904
TI  - White matter damage in asymptomatic patients with sickle cell anemia: screening
      with diffusion tensor imaging.
AB  - BACKGROUND AND PURPOSE: Ischemic injury to the brain is a common complication of
      SCA. To better understand the neurologic impact of SCA, TBSS were applied to DTI
      data to investigate white matter injuries in pediatric patients with SCA.
      MATERIALS AND METHODS: TBSS comparisons of a range of anisotropy and diffusion
      measures were carried out between age- and background-matched population groups:
      patients with SCA with no visible lesions, patients with SCA with mild gliosis,
      and normal controls. RESULTS: TBSS analysis revealed that both SCA populations
      exhibited reduced anisotropy and increased diffusivity compared with normal
      controls in multiple brain regions, including the corpus callosum and centrum
      semiovale. Furthermore, the results suggest that the severity of SCA is
      positively correlated with the white matter changes in the corpus callosum.
      CONCLUSIONS: The study demonstrates that TBSS is a viable technique in detecting
      subtle white matter damage in patients with SCA whose conventional anatomic MR
      imaging scans show no, or minimal, abnormalities and has the potential to
      evaluate the neurologic impact of the treatment of SCA.

PMID- 22595905
TI  - Case report of cytomegalovirus retinitis in an HIV-positive patient with a CD4
      count nadir of 254 cells per MUl.

PMID- 22595906
TI  - Visual impairment in the 40- to 64-year-old population of Shahroud, Iran.
AB  - PURPOSE: To determine the prevalence of visual impairment by age and gender in
      Shahroud. METHODS: Using random cluster sampling, 6311 Shahroud inhabitants who
      were between 40 and 64 years old were invited for ophthalmological examinations.
      Visual acuity worse than 0.5 LogMAR (20/60) and 1.3 LogMAR (20/400) in the better
      eye was regarded as low vision and blindness, respectively. The cause of
      blindness was determined by an ophthalmologist and in a person with more than one
      cause, the most correctable cause was regarded as the main cause. RESULTS: This
      study was conducted on 5190 participants (response rate: 82.2%). On the basis of
      presenting visual acuity, the prevalence of low vision and blindness was found to
      be 1.8% (95% confidence interval (CI): 1.4-2.10) and 0.5% (95% CI: 0.3-0.7),
      respectively. Based on corrected vision, these values were 0.5% (95% CI: 0.3-0.7)
      and 0.3% (95% CI: 0.1-0.4), respectively. Visual impairment increased with age in
      women (P<0.001). Uncorrected refractive errors (63.9%), cataract (20.2%), and
      amblyopia (5.9%) were the most common causes of visual impairment based on
      presenting vision. Based on corrected vision, however, cataract (42.5%),
      amblyopia (12.5%), and retinitis pigmentosa (7.5%) were the most common causes of
      visual impairment. CONCLUSION: Although the prevalence of visual impairment in
      the city of Shahroud was determined to be lower than two previous studies in the
      country, correction of refractive errors and cataract could minimize the rate of
      visual impairment in this population as they were shown to comprise 85% of the
      causes of visual impairment. The elderly women need to receive more attention.

PMID- 22595907
TI  - Vitreous surgery for macular hole-related retinal detachment after
      phacoemulsification cataract extraction: 10-year retrospective review.
AB  - PURPOSE: To evaluate the visual and anatomical results of surgery for macular
      hole-related retinal detachment (MHRD) after phacoemulsification cataract
      extraction. METHODS: Data for all patients who underwent surgery for MHRD after
      phacoemulsification cataract extraction from 1 December 1998 to 30 September 2008
      in one hospital were evaluated. Patient characteristics, best-corrected visual
      acuity (VA) preoperatively and at last examination, surgical technique,
      anatomical success, and follow-up period were extracted and analysed
      statistically. RESULTS: A total of 13 625 eyes of 10 076 patients who had
      phacoemulsification cataract surgery were included. In the follow-up period, 10
      cases of MHRD in nine patients were observed, of which seven eyes had high
      myopia. The mean axial length was 30.97 +/- 1.36 mm (29.19, 32.97) and mean
      myopia was-19.35 +/- 1.93 (-7.5,-3.5) dioptres. Overall anatomical success was
      achieved in 90% (9 out of 10 eyes). There was no statistically significant
      difference (P=0.240) between the logarithm of the MAR VA before the
      phacoemulsification cataract extraction and after MHRD surgical repair. VA
      increased in three eyes but decreased in the other seven after MHRD surgery.
      CONCLUSIONS: As a primary procedure, vitreous surgery combined with other
      necessary adjunct procedures such as membrane peeling and retinal tamponade seems
      to be successful in achieving anatomical success. However, VA improvement is
      dependent on the type of macular lesion and not the surgical procedure.

PMID- 22595908
TI  - Long-term outcome of intravitreal anti-vascular endothelial growth factor therapy
      with bevacizumab or ranibizumab as primary treatment for subfoveal myopic
      choroidal neovascularization.
AB  - PURPOSE: To evaluate the long-term efficacy of intravitreal anti-vascular
      endothelial growth factor (anti-VEGF) therapy as primary treatment for subfoveal
      myopic choroidal neovascularization (CNV). METHODS: In all, 37 treatment-naive
      eyes of 37 patients with subfoveal myopic CNV who received intravitreal
      bevacizumab (n=22) or ranibizumab (n=15) injections with at least 2 years of
      follow-up were reviewed. All eyes received initial three loading doses of anti
      VEGF at monthly intervals and retreatment was performed in persistent or
      recurrent CNV. Multivariate regression analyses were performed to determine the
      prognostic factors for visual outcome. RESULTS: The mean age was 57.3 years and
      the mean refractive error was -11.7 D. For all eyes, the mean logMAR best
      corrected visual acuity improved from 0.86 (20/145) at baseline to 0.48 (20/60)
      at 2 years (P<0.001). The mean visual improvement for the bevacizumab and
      ranibizumab groups at 2 years was 2.8 and 5.1 lines, respectively (P=0.073).
      There was no significant difference in the proportion of eyes having visual gain
      of three or more lines or visual loss of three or more lines between the two
      groups. The mean number of injections was 3.8 for both bevacizumab and
      ranibizumab groups. Multivariate analyses showed that eyes with higher myopic
      refractive error were less likely to have visual gain after treatment (P=0.043),
      while size of CNV was negatively correlated with mean change in vision (P=0.046).
      CONCLUSIONS: Intravitreal anti-VEGF therapy resulted in long-term visual
      improvement in myopic CNV. The treatment efficacy in terms of visual gain and
      number of retreatment appeared to be similar between bevacizumab and ranibizumab.

PMID- 22595909
TI  - Brow ptosis: are we measuring the right thing? The impact of surgery and the
      correlation of objective and subjective measures with postoperative improvement
      in quality-of-life.
AB  - INTRODUCTION: To assess the effect of brow ptosis on visual function and quality
      of-life (QoL), and to determine what measures are associated with post-surgical
      change in functional status. METHODS: Prospective longitudinal study. Fifteen
      consecutive patients undergoing brow-lift surgery from February 2009 to August
      2010. MAIN OUTCOME MEASURES: pre- and post-operative eyelid position (ie,
      distance mm from corneal reflex to upper skin fold (FRD1), lowest brow hair to
      lower limbus (LLB), centre of lower lid to upper lid skin fold (LLF)) and number
      of points missing in 'superior' and 'superior plus elsewhere' Humphrey 120-point
      visual field, as well as a Quality-of-life and Visual Function questionnaire
      before and after brow lift surgery. RESULTS: The strongest correlation between
      pre-op functional index score and any pre-op objective measure was visual fields
      (r=-0.46, P<0.085). There was a mean 36-point increase in functional index score
      after brow lift surgery (P<0.001).Self-reported preoperative functional
      impairment was the only outcome measure significantly (and strongly) associated
      with post-surgical improvement in functional status (r=-0.833, P<0.001).
      CONCLUSIONS: Surgical repair of brow ptosis results in a measurable increase in
      health-related QoL. The preoperative QoL score is the best predictor of
      postoperative improvement in QoL. The best available objective preoperative
      parameter for indicating postoperative QoL improvement is visual fields. These
      two measures should be used to better predict successful surgical outcomes.

PMID- 22595910
TI  - Workload, referral characteristics and consultation outcomes of out-of-hours
      ophthalmology services.

PMID- 22595912
TI  - Complexation of Cm(III) with 6-(5,6-dipentyl-1,2,4-triazin-3-yl)-2,2'-bipyridine
      studied by time resolved laser fluorescence spectroscopy.
AB  - The complexation of Cm(III) with 6-(5,6-dipentyl-1,2,4-triazin-3-yl)-2,2'
      bipyridine (C(5)-hemi-BTP) in a water-2-propanol solution is investigated by
      TRLFS. Upon increasing the concentration of C(5)-hemi-BTP in the Cm(III)
      solution, three different species, the 1:1-, 1:2- and 1:3-complex, with emission
      bands at 599.9 nm, 607.3 nm, and 612.8 nm, respectively, are found. Hereby, slow
      complexation kinetics is observed which no other BTP-type ligand has shown up to
      now. The species distributions for various ligand concentrations are determined
      and stability constants are derived (log beta(03) = 12.1 +/- 0.1). As extraction
      with hemi-BTP ligands is only possible in the presence of a lipophilic anion, the
      complexation of Cm(III) with C(5)-hemi-BTP and 2-bromohexanoic acid is
      investigated to deduce the species formed in the extraction process. It is found
      that Cm(III) is coordinated by two C(5)-hemi-BTP ligands and one 2-bromohexanoate
      ligand. This species formed in aqueous solution is identical to the one from the
      extraction process.

PMID- 22595911
TI  - High molecular weight hyaluronan decreases oxidative DNA damage induced by EDTA
      in human corneal epithelial cells.
AB  - PURPOSE: To investigate the toxic effects of ethylenediaminetetraacetic acid
      disodium salt (EDTA), a corneal penetration enhancer in topical ophthalmic
      formulations, on DNA in human corneal epithelial cells (HCEs), and to investigate
      whether the effect induced by EDTA can be inhibited by high molecular weight
      hyaluronan (HA). METHODS: Cells were exposed to EDTA in concentrations ranging
      from 0.00001 to 0.01% for 60 min, or 30 min high molecular weight HA pretreatment
      followed by EDTA treatment. The cell viability was measured by the MTT test. Cell
      apoptosis was determined with annexin V staining by flow cytometry. The DNA
      single- and double-strand breaks of HCEs were examined by alkaline comet assay
      and by immunofluorescence microscope detection of the phosphorylated form of
      histone variant H2AX (gammaH2AX) foci, respectively. Reactive oxygen species
      (ROS) production was assessed by the fluorescent probe, 2', 7'
      dichlorodihydrofluorescein diacetate. RESULTS: EDTA exhibited no adverse effect
      on cell viability and did not induce cell apoptosis in human corneal epithelial
      cells at concentrations lower than 0.01%. However, a significant increase of DNA
      single- and double-strand breaks was observed in a dose-dependent manner with all
      the concentrations of EDTA tested in HCEs. In addition, EDTA treatment led to
      elevated ROS generation. Moreover, 30 min preincubation with high molecular
      weight HA significantly decreased EDTA-induced ROS generation and DNA damage.
      CONCLUSIONS: EDTA could induce DNA damage in HCEs, probably through oxidative
      stress. Furthermore, high molecular weight HA was an effective protective agent
      that had antioxidant properties and decreased DNA damage induced by EDTA.

PMID- 22595913
TI  - Multidrug-resistant clones of community-associated meticillin-resistant
      Staphylococcus aureus isolated from Chinese children and the resistance genes to
      clindamycin and mupirocin.
AB  - This study aimed to correlate the multidrug resistance (MDR) and sequence type
      (ST) clones of community-associated (CA) meticillin-resistant Staphylococcus
      aureus (MRSA) to identify the genes responsible for clindamycin and mupirocin
      resistance in S. aureus isolates from paediatric hospitals in mainland China. A
      total of 435 S. aureus isolates were collected. Compared with CA meticillin
      susceptible S. aureus (MSSA), the resistance rates of CA-MRSA to ciprofloxacin,
      chloramphenicol, gentamicin and tetracycline were higher (19.0 vs 2.6 %, P<0.001;
      14.7 vs 3.1 %, P<0.001; 14.7 vs 3.1 %, P<0.01; and 46.0 vs 13.3 %, P<0.001,
      respectively). Compared with hospital-associated (HA)-MRSA, the resistance rates
      of CA-MRSA to ciprofloxacin, gentamicin, rifampicin, tetracycline and
      trimethoprim-sulfamethoxazole were lower (19 vs 94.8 %, P<0.001; 14.7 vs 84.4 %,
      P<0.001; 5.5 vs 88.3 %, P<0.001; 46 vs 94.8 %, P<0.001; and 1.8 vs 9.1 %, P<0.01,
      respectively). The resistance rates of CA-MRSA, HA-MRSA and CA-MSSA to
      clindamycin (92.0, 77.9 and 64.1 %, respectively) and erythromycin (85.9, 77.9
      and 63.1 %, respectively) were high. The MDR rates (resistance to three or more
      non-beta-lactams) were 49.6, 100 and 14 % in the CA-MRSA, HA-MRSA and CA-MSSA
      isolates, respectively. Five of seven ST clones in the CA-MRSA isolates, namely
      ST59, ST338, ST45, ST910 and ST965, had MDR rates of >50 % (67.9, 87.5, 100, 50
      and 83.3 %, respectively). The constitutive phenotype of macrolide-lincosamide
      streptogramin B (MLS(B)) resistance (69 %) and the ermB gene (38.1 %)
      predominated among the MLS(B)-resistant CA S. aureus strains. The resistance rate
      to mupirocin was 2.3 % and plasmids carrying the mupA gene varied in size between
      23 and 54.2 kb in six strains with high-level resistance as determined by
      Southern blot analysis. The present study showed that resistance to non-beta
      lactams, especially to clindamycin, is high in CA-MRSA isolates from Chinese
      children and that the profile of resistance is related to clonal type. This study
      revealed distinctive patterns of MLS(B)-resistant genes among CA S. aureus
      isolates.

PMID- 22595914
TI  - Adherence of Clostridium difficile spores to Caco-2 cells in culture.
AB  - Clostridium difficile is the causative agent of the majority of antibiotic
      associated diarrhoea cases. C. difficile spores are recognized as the persistent
      and infectious morphotype as well as the vehicle of transmission of CDI. However,
      there is a lack of knowledge on how C. difficile spores interact with the host's
      epithelial surfaces. In this context, we have characterized the ability of C.
      difficile spores to adhere to human Caco-2 cells. Despite the similarities in
      spore-surface hydrophobicity between spores of C. difficile and Clostridium
      perfringens (another enteric pathogen that also sporulates in the gut), spores of
      C. difficile adhere better to Caco-2 cells. Adherence to Caco-2 cells was
      significantly reduced when C. difficile spores were treated with trypsin.
      Sonication of C. difficile spores altered the ultrastructure of the outermost
      exosporium-like structure, releasing two protein species of ~40 kDa and
      significantly reduced spore hydrophobicity and adherence to Caco-2 cells. Using a
      trifunctional cross-linker, we were able to co-immunoprecipitate four protein
      species from the surface of Caco-2 cells. In conclusion, this study provides
      evidence that C. difficile spores adhere to human intestinal enterocyte-like
      cells through spore- and enterocytic-surface-specific ligand(s) and/or
      receptor(s).

PMID- 22595915
TI  - Theoretical predictions of a bucky-diamond SiC cluster.
AB  - A study  of structural relaxations of Si(n)C(m) clusters corresponding to
      different compositions, different relative arrangements of Si/C atoms, and
      different types of initial structure, reveals that the Si(n)C(m) bucky-diamond
      structure can be obtained for an initial network structure constructed from a
      truncated bulk 3C-SiC for a magic composition corresponding to n = 68 and m = 79.
      This study was performed using a semi-empirical Hamiltonian (SCED-LCAO) since it
      allowed an extensive search of different types of initial structures. However,
      the bucky-diamond structure predicted by this method was also confirmed by a more
      accurate density functional theory (DFT) based method. The bucky-diamond
      structure exhibited by a SiC-based system represents an interesting paradigm
      where a Si atom can form three-coordinated as well as four-coordinated networks
      with carbon atoms and vice versa and with both types of network co-existing in
      the same structure. Specifically, the bucky-diamond structure of the Si(68)C(79)
      cluster consists of a 35-atom diamond-like inner core (four-atom coordinations)
      suspended inside a 112-atom fullerene-like shell (three-atom coordinations).

PMID- 22595916
TI  - Will brief interventions in primary care change the heavy drinking culture in New
      Zealand?

PMID- 22595917
TI  - Are two internal thoracic artery grafts as safe as one?

PMID- 22595918
TI  - Avoidable complications following chest tube insertion.

PMID- 22595920
TI  - Is routine alcohol screening and brief intervention feasible in a New Zealand
      primary care environment.
AB  - AIM: To test the feasibility of a systemised ABC alcohol screening and brief
      intervention (SBI) approach in general practice in a New Zealand region. METHOD:
      Data were collected on patients over 15 years who had their alcohol status
      recorded using the AUDIT tool. A concurrent independent process evaluation was
      conducted to assess effectiveness of ABC alcohol SBI related training and
      implementation of intervention. RESULTS: In an 8-month period, general practices
      in the Whanganui region documented alcohol consumption of 43% of their patients.
      Of the 43% of patients screened 24% were drinking contrary to ALAC's low risk
      drinking advice. Of these, 36% received brief advice or referral. Success of the
      approach can be attributed to the use of the Patient Dashboard reminder software
      and linked alcohol recording form. Other success factors included the use of a
      clinical champion and project leader, education and training, funding for extra
      GP and nurse assessment time and linking of the ABC alcohol SBI approach to
      existing services. CONCLUSION: Primary care in Whanganui has demonstrated the
      capacity to routinely query patient alcohol use and offer brief advice. If the
      approach was more widely adopted, there is considerable scope for general
      practice nationally to address potentially harmful patient alcohol use.

PMID- 22595921
TI  - Chest tube drainage of pleural effusions--an audit of current practice and
      complications at Hutt Hospital.
AB  - AIMS: The aims of the study were to review small-bore chest tube insertion
      practices for drainage of pleural fluid at Hutt Valley District Health Board
      (HVDHB), to assess complications, and compare the findings with international
      data. METHODS: Retrospective analysis of clinical records was completed on all
      chest tube insertions for drainage of pleural fluid at HVDHB from December 2008
      to November 2009. Descriptive statistics were used to present demographics and
      tube-associated complications. Comparison was made to available similar
      international data. RESULTS: Small-bore tubes comprised 59/65 (91%) chest tube
      insertions and 23/25 (92%) complications. Available comparative data was limited.
      Ultrasound was used in 36% of insertions. Nearly half of chest drains placed for
      empyema required subsequent cardiothoracic surgical intervention. CONCLUSIONS:
      Chest drain complication rates at HVDHB were comparable to those seen
      internationally. Referral rates to cardiothoracic surgery for empyema were within
      described ranges. The importance of procedural training for junior medical staff,
      optimising safety of drain insertions with ultrasound guidance, and clear
      clinical governance for chest tube insertions are important in minimising harm
      from this procedure. Specialist societies need to take a leadership in providing
      guidance on chest drain insertions to secondary and tertiary hospitals in
      Australia and New Zealand.

PMID- 22595922
TI  - Are two internal thoracic artery grafts as safe as one? Experience from Green
      Lane Hospital.
AB  - AIM: To compare short-term mortality and major morbidity between patients
      undergoing elective primary isolated CABG with bilateral internal thoracic artery
      (BITA) or single internal thoracic artery (SITA) grafts at Green Lane Hospital
      (Auckland, New Zealand). METHODS: We conducted a retrospective study of short
      term outcomes in 5955 patients receiving SITA and 637 patients receiving BITA
      grafts between 1990 and 2004. Only patients undergoing elective primary isolated
      coronary artery surgery were included. The primary outcome was a composite end
      point (early death, perioperative MI, reoperation for sternal wound complications
      or significantly prolonged hospital stay). Patients receiving BITA grafts were
      case-matched with patients receiving SITA grafts for confounding factors and
      comparison was made between perioperative outcomes in the two groups. RESULTS:
      After case-matching, no statistically significant difference was found in the
      incidence of our primary endpoint between patients receiving BITA versus SITA
      grafts [odds ratio 0.84 (95% CI 0.59, 1.21)]. Furthermore, there was no
      difference in rates of reoperation for sternal wound complications between the
      two groups [odds ratio 1.00 (95% CI 0.29, 3.44)]. CONCLUSIONS: Given the
      potential long-term clinical advantages of BITA grafting, our results support the
      increased use of BITA grafts in selected patients.

PMID- 22595923
TI  - An evaluation of a pictorial asthma medication plan for Pacific children.
AB  - BACKGROUND: The burden of asthma falls disproportionately on children from New
      Zealand's Pacific communities. Guidelines recommend pictorial resources but these
      have not been evaluated in this population. AIMS: Evaluate a pictorial asthma
      medication plan focusing on regular 'everyday' inhaler use and a signs and
      symptoms sheet for Pacific children; the primary outcome measure was continued
      use of resources after 6 months. METHODS: Resources were provided to families
      with face-to-face education at a general practice or inpatient setting in West
      Auckland. A questionnaire about the resources was completed after 6 weeks, and an
      audit regarding use after 6 months. RESULTS: Data from 48 children were analysed
      (Samoan, n=31); 45 English and 22 first language versions (Samoan, Tongan,
      Tuvaluan) were used; median time to questionnaire completion was 48 days. The
      pictorial asthma medication plan was acceptable to families, effective at
      reinforcing the importance of 'everyday' inhalers, and a reminder for regular
      use; the signs and symptoms sheets were informative and improved self-efficacy;
      93% of families were using the resources after 6 months. An increase in
      'everyday' inhaler use was observed after education. CONCLUSION: The resources
      were effective at improving inhaler knowledge and supporting symptom recognition.
      A 'less-is-more' approach, pictorial format, and first language availability are
      characteristics that may benefit other ethnicities.

PMID- 22595925
TI  - Did an acute medical assessment unit improve the initial assessment and treatment
      of community acquired pneumonia--a retrospective audit.
AB  - AIM: Medical Assessment and Planning Units (MAPUs) are proposed as a means to
      treat medically unwell patients in a timely and clinically appropriate manner,
      thus improving quality, facilitating safe early discharge, and reducing
      congestion in emergency departments. This study assessed the impact of opening a
      MAPU on the initial assessment and treatment of patients with community-acquired
      pneumonia (CAP). METHOD: A retrospective audit of patients presenting to
      Wellington Hospital was conducted from January to March 2009 and January to March
      2010, straddling the opening of a MAPU. Outcome measures included timeliness of
      assessment, indicators of clinical quality, length of stay, recommended follow-up
      and mortality. RESULTS: MAPU referred patients were less unwell and younger.
      Times to first doctor assessment and X-ray were longer than in the Emergency
      Department (ED) following the introduction of the MAPU; time to physician review
      for all admitted patients was unchanged compared to before the opening of the
      MAPU. Compliance with other aspects of evidence based guidelines was patchy and
      showed no improvement following the opening of the MAPU. Most patients whose
      length of stay was short were appropriately admitted to the MAPU. CONCLUSION: The
      MAPU has successfully streamed a cohort of less unwell patients away from the ED.
      Opportunity exists to improve the timeliness of treatment and compliance with
      guidelines. A disease-specific audit has served as a useful adjunct to other
      approaches to assessing a unit's impact.

PMID- 22595924
TI  - Unusually virulent coagulase-negative Staphylococcus lugdunensis is frequently
      associated with infective endocarditis: a Waikato series of patients.
AB  - BACKGROUND: Staphylococcus lugdunensis, a species of coagulase-negative
      staphylococci is associated with a wide variety of infections ranging from mild
      skin and soft tissue infections to serious infections which include brain
      abscess, chronic osteomyelitis and infective endocarditis. The aim of this study
      was to review cases of S. lugdunensis bacteraemia isolated from a New Zealand
      tertiary institution and describe the clinical presentation, diagnosis and
      treatment of the patients. METHODS: All blood cultures reported positive for S.
      lugdunensis from the Microbiology Laboratory, Waikato Hospital, New Zealand
      between March 2006 to April 2011 were reviewed. RESULTS: A total of 11 cases of
      S. lugdunensis bacteraemia were identified during the 5-year period. Three (27%)
      cases were due to infective endocarditis with one delayed diagnosis due to the
      failure of recognize the coagulase-negative Staphylococcus. Transthoracic or
      transoesophageal echocardiography was performed in 6 (55%) of the patients. One
      patient with endocarditis required early surgery and the other two were managed
      successfully with intravenous antibiotics. There was no in hospital mortality in
      the patients with endocarditis. The remaining 8 cases included 1 (9%) necrotizing
      fasciitis, 1 (9%) immunocompromised nosocomial multiple organism sepsis, 1 (9%)
      deep tissue infection requiring 6 weeks of intravenous antibiotics, 2 (18.5%)
      superficial skin infection, 1 (9%) nosocomial post-pacemaker insertion infection
      and 2 (18.5%) had fever of unknown origin. All isolates were sensitive to
      Flucloxacillin and Vancomycin. Overall the survival rate of the acute
      presentation and treatment was 91% (10/11). CONCLUSION: Three of our 11 patients
      (27%) with S. lugdunensis bacteraemia were diagnosed with infective endocarditis.
      Evaluation for endocarditis is therefore advised in patients who have positive
      blood culture for this organism.

PMID- 22595926
TI  - Old man's friend? Resuscitation decisions in patients hospitalised with
      pneumonia.
AB  - BACKGROUND: Community-acquired pneumonia (CAP) is a common illness, for which
      hospitalisation leads to significant inpatient and subsequent mortality. The
      frequency and timing of discussion of end-of-life issues with these inpatients is
      therefore relevant. AIM: To determine whether end-of-life discussions occurred
      for patients with CAP whose prognostic indicators suggested a high risk of dying.
      METHODS: A retrospective review of 155 admissions with CAP was conducted. The
      nature and timing of resuscitation decisions were correlated with age, illness
      severity and mortality. RESULTS: Mortality following admission with CAP increases
      with age and severity. Of those over 65, 37% die within 12 months of discharge;
      11% die on the index admission, and a further 26% die in the 12 months following
      discharge. Mortality increases dramatically with older age: those over 80 had a
      47% 12-month mortality. End-of-life decisions were documented prior to death for
      all inpatient deaths. However, end-of-life decisions were only documented in a
      minority of other cases, even amongst those with highest risk of subsequent
      mortality. CONCLUSIONS: In a common illness with significant mortality,
      opportunity exists to better identify those at high risk of mortality and
      initiate discussions about end-of-life care. A not-for-resuscitation discussion
      currently appears to function as a surrogate marker for impending death rather
      than an opportunity to elicit a patient's wishes for their care should they be at
      high risk of dying in the near future.

PMID- 22595927
TI  - Implementing and sustaining a hand hygiene culture change programme at Auckland
      District Health Board.
AB  - AIM: In January 2009 Auckland District Health Board commenced implementation of
      the Hand Hygiene New Zealand (HHNZ) programme to bring about a culture change and
      to improve hand hygiene compliance by healthcare workers. We describe the
      implementation process and assess the effectiveness of this programme 36 months
      after implementation. METHOD: In keeping with the HHNZ guideline the
      implementation was divided into five steps: roll-out and facility preparation,
      baseline evaluation, implementation, follow-up evaluation and sustainability. The
      process measure was improvement in hand hygiene compliance and the outcome
      measure was Staphylococcus aureus clinical infection and bacteraemia rates.
      RESULTS: The mean (95% CI; range) baseline compliance rates for the national
      reporting wards was 35% (95% CI 24-46%, 25-61%). The overall compliance by the
      7th audit period was 60% (95% CI 46-74; range 47-91). All healthcare worker
      groups had improvement in compliance. The reduction in healthcare-associated S.
      aureus bacteraemia rates following the implementation was statistically
      significant (p=0.027). CONCLUSION: Compliance with hand hygiene improved
      following implementation of a culture change programme. Sustaining this
      improvement requires commitment and strong leadership at a senior level both
      nationally and within each District Health Board.

PMID- 22595928
TI  - The further and future evolution of the New Zealand Immunisation Schedule.
AB  - MeNZB was introduced to control meningococcal disease in New Zealand in 2004 and
      routine use ceased in 2008. In that year, two new vaccines were added to the New
      Zealand Childhood Immunisation Schedule, pneumococcal and human papilloma virus,
      and two more, varicella and rotavirus, have been recommended but not funded. By
      comparison, in the 16 years prior to 2006 only one new vaccine was introduced,
      Haemophilus influenzae type B. Coverage is improving and is now around 90%,
      making timeliness an important target and supplementary strategies for
      controlling pertussis of greater importance. A personal view of each of these
      vaccines is provided in this article.

PMID- 22595929
TI  - Mondor's disease in a patient previously treated for breast carcinoma in situ: a
      case report.
AB  - Mondor's disease is a thrombophlebitis that affects mainly the superficial veins
      of the breast. The aetiology of Mondor's disease is multifaceted and there are
      reports in the literature of an association between Mondor's disease and breast
      cancer. This disease occurs more commonly in women than men, mainly in the third
      and fourth decades of life, leading to a spontaneous remission in most cases. We
      report a case of a 45-year-old female patient that had been treated for breast
      carcinoma in situ.

PMID- 22595930
TI  - Medical image. Half-and-half nail.

PMID- 22595931
TI  - Breast thermography review--and author response.

PMID- 22595932
TI  - Survey of hot water temperatures in campgrounds: elevated scalding risk and
      energy wastage.

PMID- 22595933
TI  - Comparison of glaucoma diagnoses using Stratus and Cirrus optical coherence
      tomography in different glaucoma types in a Chinese population.
AB  - PURPOSE: To compare the glaucoma diagnostic power of Stratus and Cirrus optical
      coherence tomographies (OCTs) in a Taiwan Chinese population with different
      glaucoma types. PATIENTS AND METHODS: One eye each was chosen from 21 ocular
      hypertension (OH) patients, 27 glaucoma-suspect (GS) patients, 35 primary open
      angle glaucoma (POAG) patients, 26 primary angle-closure glaucoma (PACG)
      patients, and 52 normal subjects. Early glaucoma (EG) was identified among
      glaucomatous eyes on the basis of the visual field severity (better than -9 dB).
      All participants were imaged using 2 OCT units at the same visit. The area under
      the receiver operator characteristic (AROC) curve was used to differentiate
      normal eyes from OH, GS, POAG, PACG, and EG eyes, and the sensitivity and
      specificity of each parameter from internal normative classifications were
      analyzed. RESULTS: For normal versus OH eyes, the best AROC value was the average
      thickness (Stratus, 0.693; Cirrus, 0.697). For normal versus GS eyes, the best
      AROC value was the average thickness (Stratus, 0.807; Cirrus, 0.776). For normal
      versus POAG eyes, the best AROC value was the average thickness (Stratus, 0.943;
      Cirrus, 0.930). For normal versus PACG eyes, the best AROC value was the 5
      o'clock hour (Stratus, 0.830; Cirrus, 0.817). For normal versus EG eyes, the best
      AROC value was the average thickness with Stratus (0.868) and the 5-o'clock hour
      with Cirrus (0.876). All sensitivities in the 5 groups were fair on the basis of
      the internal normal classification database of both OCTs. CONCLUSIONS: Cirrus and
      Stratus OCTs showed equal diagnostic power in EG, OH, GS, POAG, and PACG eyes in
      a Taiwan Chinese population. The utility of the current internal databases of
      both OCT units for the Chinese population is an interesting issue that needs to
      be addressed in the future.

PMID- 22595934
TI  - An evaluation of therapeutic noninferiority of 0.005% latanoprost ophthalmic
      solution and xalatan in patients with glaucoma or ocular hypertension.
AB  - PURPOSE: To assess the therapeutic noninferiority of 0.005% latanoprost
      ophthalmic solution versus Xalatan in the treatment of patients with primary open
      angle glaucoma or ocular hypertension. PATIENTS AND METHODS: This was a double
      masked, randomized, multicenter study. A total of 184 patients with a diagnosis
      of unilateral or bilateral primary open-angle glaucoma or ocular hypertension
      were randomly assigned to either 0.005% latanoprost ophthalmic solution or
      Xalatan for 12 weeks. The primary end-point was the change in intraocular
      pressure (IOP) at 12 weeks in the 2 groups. Noninferiority was reached if the 2
      sided 95% confidence intervals (CI) for the difference between adjusted treatment
      means were entirely within the interval from -1.5 to +1.5 mm Hg. RESULTS: The
      difference between treatments in the change of IOP from baseline to the end of
      treatment was 0.12 mm Hg (95% CI: -0.47, 0.71) in the intention-to-treat
      population and 0 mm Hg (95% CI: -0.58, 0.57) in the per protocol population.
      There was no statistically significant difference between the 2 groups in terms
      of drug-related adverse events. The most commonly reported drug-related local
      adverse events were: ocular hyperemia, eyelashes growth, and eye irritation.
      CONCLUSIONS: This study demonstrates that 0.005% latanoprost ophthalmic solution
      is noninferior to Xalatan in lowering IOP and is generally well tolerated.

PMID- 22595935
TI  - Angle closure after Boston keratoprosthesis.
AB  - PURPOSE: To evaluate changes in the anterior chamber angle after Boston
      keratoprosthesis (KPro) placement. PATIENTS/METHODS: Ten patients were serially
      imaged with anterior segment optical coherence tomography after Boston KPro
      surgery. Angles were judged to be open or closed in the horizontal axis. RESULTS:
      Seven of 10 patients had open angles before KPro placement. Within 4 months, 4 of
      7 patients developed angle closure. Contact between the iris and the backplate
      was seen in 3 of these patients. Two of the 4 eyes demonstrated progressive angle
      closure. Intraocular pressure was elevated in 3 patients postoperatively due to
      the obstruction of a glaucoma drainage device tube (1 eye) and angle closure (2
      eyes). CONCLUSIONS: After Boston KPro surgery, patients must be carefully
      monitored for the onset or progression of glaucoma. Progressive angle closure can
      occur after placement of a Boston KPro and may be seen in conjunction with irido
      backplate touch.

PMID- 22595936
TI  - Relationship between intraocular pressure and rate of visual field progression in
      treated glaucoma.
AB  - PURPOSE: To evaluate the relationship between intraocular pressure (IOP) and the
      rate of visual field (VF) progression in treated glaucoma. METHODS: In a clinic
      based, retrospective study, data of consecutive primary open-angle and angle
      closure glaucoma patients with >= 5 VFs between 1989 and 2008 were analyzed. The
      Guided Progression Analysis software, which provides the rate of change of Visual
      Field Index per year, was used to assess the rate of progression (ROP). IOP
      measurements during the VF examination visits were extracted, and mean, peak, and
      fluctuation (SD) of IOP during the follow-up were calculated. Relationships
      between IOP parameters and ROP were analyzed using regression models. Other risk
      factors evaluated were age, sex, type of glaucoma, presence of hypertension and
      diabetes, severity of VF loss at presentation, glaucoma surgery during follow-up,
      number of antiglaucoma medications, and follow-up duration. RESULTS: During the
      study period, 296 eyes of 213 glaucoma patients had undergone >= 5 VFs. IOP
      fluctuation was the only IOP parameter significantly associated with ROP (beta=
      0.37, P=0.02). Evaluated in a multivariate model with other risk factors, the
      severity of VF damage at presentation (beta=0.08, P=0.002) and IOP fluctuation
      (beta=-0.35, P=0.02) remained significantly associated with ROP. Greater IOP
      fluctuation was seen in eyes undergoing glaucoma surgery and eyes requiring more
      antiglaucoma medications during follow-up. CONCLUSIONS: Long-term IOP fluctuation
      was the most important IOP parameter associated with increased ROP of
      glaucomatous VF loss. This association is likely due to the confounding effect of
      enhanced therapy in eyes suspected to be progressing.

PMID- 22595937
TI  - Effect of Ginkgo biloba extract on visual field progression in normal tension
      glaucoma.
AB  - PURPOSE: To evaluate the long-term effect of Ginkgo biloba extract (GBE) on
      progression of visual field (VF) defects in patients with normal tension glaucoma
      (NTG). METHODS: Forty-two eyes of 42 patients with treated NTG who received 80 mg
      GBE 2 times daily and who had at least 5 VF tests using the Humphrey Visual Field
      Analyzer for more than a 4-year period before and after GBE treatment were
      evaluated in this retrospective study. We evaluated the change of progression
      rate using mean deviation (MD), pattern standard deviation (PSD), and visual
      field index (VFI) after GBE treatment. The time course of mean total deviation in
      10 zones corresponding to the glaucoma hemifield test was analyzed using a linear
      mixed effects model with unequal random effect variances. RESULTS: The mean
      follow-up period was 12.3 years. The posttherapeutic intraocular pressures before
      and after GBE treatment were not significantly different (P=0.509 paired t test).
      Before GBE treatment, the regression coefficients (RCs) of MD, PSD, and VFI
      change were -0.619 dB/y, 0.626 dB/y, and -2.153%/y, respectively. After GBE
      treatment, the RCs of MD, PSD, and VFI change improved significantly to -0.379
      dB/y, 0.342 dB/y, and -1.212%/y (P <0.001), respectively. In zone 1, the RC of
      mean total deviation change was significantly increased after GBE administration
      (P <0.005). CONCLUSIONS: GBE administration slowed the progression of VF damage
      in patients with NTG, especially in zone 1 corresponding to the superior central
      field.

PMID- 22595938
TI  - Estimate of de novo mutation frequency in probands with PTEN hamartoma tumor
      syndrome.
AB  - PURPOSE: PTEN hamartoma tumor syndrome is an autosomal dominant disorder with
      increased risks of neoplasias, macrocephaly, and developmental disabilities.
      While both familial and sporadic cases exist, actual de novo mutation frequency
      remains unknown. We sought to estimate this within our PTEN-mutation positive
      patient series. METHODS: Patients were prospectively accrued if they had known
      pathogenic germline PTEN mutations or phenotypic features suspicious for PHTS.
      Only families with pathogenic PTEN mutations were included. Likelihood for de
      novo mutation was graded from 1 (confirmed inherited) to 5 (confirmed de novo)
      based on family history and mutation status. Fisher's two-tailed exact and
      unpaired t-tests were used to compare between groups. RESULTS: 187 pathogenic
      PTEN-mutation positive families were eligible for this study. De novo (grade 5)
      status was confirmed in 20 (10.7%) probands, and in 36 (19.3%) was suspected
      based on family history. Demographics, mutations, and phenotypes were similar for
      probands graded 1 vs. 5 (all P > 0.06). In grade 1 probands, mutations were
      inherited equally from maternal and paternal lineages (P = 0.55). CONCLUSIONS:
      The frequency of de novo PTEN mutation is at minimum 10.7% and at best 47.6%.
      Absence of PHTS features within a family history should not preclude
      consideration of this diagnosis for patients with relevant personal history.

PMID- 22595939
TI  - Identification of a novel Cys146X mutation of SOD1 in familial amyotrophic
      lateral sclerosis by whole-exome sequencing.
AB  - PURPOSE: Familial amyotrophic lateral sclerosis has been linked to mutations in
      15 genes, and it is believed these genes account for less than 20-30% of Chinese
      patients with familial amyotrophic lateral sclerosis. Of the 163 different
      superoxide dismutase 1 gene mutations in amyotrophic lateral sclerosis 1, only
      6.1% of them were from individuals of Chinese origin. Therefore, to quickly learn
      the causative gene for patients with familial amyotrophic lateral sclerosis in a
      Chinese pedigree, we opted to apply whole-exome sequencing as a diagnostic tool.
      METHODS: To avoid time-consuming screening of known familial amyotrophic lateral
      sclerosis candidate genes by PCR-Sanger sequencing, we conducted whole-exome
      sequencing toward selected individuals of a four-generation familial amyotrophic
      lateral sclerosis family. RESULTS: Patients in the family showed autosomal
      dominant features, as well as a mean onset age of 35.3 years, and a mean duration
      of 2.1 years. By deep sequencing analysis, we identified a novel p.Cys146X SOD1
      mutation in all examined patients. Genotype-phenotype and SOD1 structural model
      analysis revealed the effects of the Cys57-Cys146 disulfide bond formation and
      the C-terminal dimer contact region on the disease phenotypes. CONCLUSION: The
      Cys146X mutation causes familial amyotrophic lateral sclerosis with severe
      phenotypes. Whole-exome sequencing becomes an attractive diagnostic tool for
      identifying causative genes, particularly for neurological disorders with unusual
      phenotypes, pleiotropic malformations, multiple known candidate genes, and
      complicated inheritance patterns.

PMID- 22595940
TI  - Diagnostic approaches to apparent homozygosity.
AB  - PURPOSE: Sanger sequencing is a mainstay for the identification of gene mutations
      used in molecular diagnostic laboratories. However, in autosomal recessive
      disorders, failure of allele amplification can occur for a variety of reasons,
      leading heterozygous mutations to appear homozygous. We sought to investigate the
      frequency at which apparently homozygous mutations detected by Sanger sequencing
      in our laboratory appeared homozygous due to other molecular etiologies. METHODS:
      A review of 12,406 cases from 40 different genetic tests that were submitted to
      the Medical Genetics Laboratories at Baylor College of Medicine for Sanger
      sequence analysis was performed. The molecular status of apparently homozygous
      cases was further investigated by testing parents using various methods. RESULTS:
      A total of 291 cases of apparent homozygosity were identified, ranging from 0 to
      37% of the total per gene. One-third of the apparently homozygous cases were
      followed up by parental testing. Parental carrier status was confirmed in 88% of
      the cases. Of the cases in which parental carrier status could not be confirmed,
      deletions encompassing point mutations, allele dropout due to single-nucleotide
      polymorphisms at primer sites, and uniparental isodisomy were observed.
      CONCLUSION: For individuals with autosomal recessive disorders and apparently
      homozygous mutations, confirmation by parental testing can rule out other causes
      of apparent homozygosity, including allele dropout, copy number variations, and
      uniparental isodisomy.

PMID- 22595941
TI  - Association between health-service use and multiplex genetic testing.
AB  - PURPOSE: The objective of this work was to examine whether offers of multiplex
      genetic testing increase health-care utilization among healthy patients aged 25
      40 years. The identification of genetic variants associated with common disease
      is accelerating rapidly. "Multiplex tests" that give individuals feedback on
      large panels of genetic variants have proliferated. Availability of these test
      results may prompt consumers to use more health-care services. METHODS: A total
      of 1,599 continuously insured adults aged 25-40 years were surveyed and offered a
      multiplex genetic susceptibility test for eight common health conditions. Health
      care utilization from automated records was compared in 12-month pre- and
      posttest periods among persons who completed a baseline survey only (68.7%),
      those who visited a study website but opted not to test (17.8%), and those who
      chose the multiplex genetic susceptibility test (13.6%). RESULTS: In the pretest
      period, persons choosing genetic testing used an average of 1.02 physician visits
      per quarter as compared with 0.93 and 0.82 for the baseline-only and Web-only
      groups, respectively (P < 0.05). There were no statistically significant
      differences by group in the pretest use of any common medical tests or procedures
      associated with four common health conditions. When changes in physician and
      medical test/procedure use in the posttest period were compared among the groups,
      no statistically significant differences were observed for any utilization
      category. CONCLUSIONS: Persons offered and completing multiplex genetic
      susceptibility testing used more physician visits before testing, but testing was
      not associated with subsequent changes in use. This study supports the
      supposition that multiplex genetic testing offers can be provided directly to the
      patients in such a way that use of health services is not inappropriately
      increased.

PMID- 22595943
TI  - Improved technique for manually constructing tissue microarrays for large-core
      arrays.
AB  - Tissue microarrays were originally developed to enable alignment of multiple
      tissue cores in a single paraffin block and to enable high-throughput laboratory
      analysis. However, a major drawback is the loss of tissue cores during slide
      preparation, especially when sectioning the tissue block. Tissue cylinders
      directly aligned in the metal box without preheating tend to detach from the
      surrounding paraffin, which results in incomplete or folded tissue sections. The
      proposed solution is preheating all tissue cylinders on a hot plate to facilitate
      fusion between the paraffin within the core and the paraffin surrounding the
      core. In this study, 6 tissue microarray blocks were constructed from 528 tissue
      cores extracted from various formalin-fixed, paraffin-embedded human tissue
      samples. The tissue cores in the arrays revealed good homogenization with the
      surrounding paraffin wax, and the tissue sections were obtained intact. Both
      hematoxylin-eosin and immunohistochemical staining confirmed satisfactory
      results. This simple and economical method is easily performed in the laboratory
      without expensive instrumentation.

PMID- 22595944
TI  - Oral squamous cell carcinoma from users and nonusers of tobacco and alcohol: 
      clinicopathologic features and immunoreactivity of VEGF, caspase-3, and p53.
AB  - OBJECTIVES: The objective of this study was to compare the clinicopathologic
      characteristics and immunoreactivity of vascular endothelial growth factor
      (VEGF), caspase-3, and p53 between oral squamous cell carcinomas from users and
      nonusers of tobacco and alcohol. DESIGN: We randomly selected 90 specimens of
      oral carcinomas, from patients diagnosed between 1991 and 2011 in Oral Medicine
      Division. The specimens were distributed into 3 groups according to exposure to
      risk factors: 30 specimens from smokers, 30 from smokers/alcohol drinkers, and 30
      from individuals not exposed to these factors. The clinicopathologic
      characteristics of the lesions were evaluated and the proteins VEGF, caspase-3,
      and p53 were detected by immunohistochemistry. RESULTS: The group of
      nonsmokers/nonalcohol drinkers consisted mainly of women (P<=0.001), with a
      higher mean age (P=0.004). The group of smokers/alcohol drinkers exhibited larger
      tumors when compared with patients not exposed to smoking and alcohol (P=0.004).
      The histopathologic grading also differed between these groups (P=0.040), because
      a greater number of grade I lesions and fewer grade III lesions were found in
      patients who were nonsmokers/nonalcohol drinkers. No significant difference was
      observed in relation to immunoreactivity of VEGF (P=0.315), caspase-3 (P=0.860),
      and p53 (P=0.876) between the groups. CONCLUSIONS: There are substantial
      clinicopathologic differences between oral carcinomas in users and nonusers of
      tobacco and alcohol. Immunodetection of the proteins VEGF, caspase-3, and p53 is
      not influenced by smoking or alcohol consumption, suggesting that other molecular
      mechanisms are associated with the biological aggressiveness of oral carcinoma in
      patients exposed to these risk factors.

PMID- 22595945
TI  - Immunohistochemistry applied to the differential diagnosis between ductal and
      lobular carcinoma of the breast.
AB  - The distinction between classic lobular and ductal carcinoma, both in situ and
      invasive, has important therapeutic and management implications. Most ductal and
      lobular carcinomas are distinguished readily on hematoxylin-eosin-stained
      sections because of distinct histomorphologic features. In cases with ambiguous
      morphologic features, however, categorization in one or another type can be a
      challenge. Several immunohistochemical markers, including epithelial cadherin,
      p120, beta-catenin, and low-molecular-weight and high-molecular-weight
      cytokeratins among others, have been introduced to help better discriminate
      between lobular neoplasia and ductal carcinoma. In this critical review of the
      literature, we comment about the usefulness and the limitations of these markers
      to improve the accuracy in the differential diagnosis of breast pathology.

PMID- 22595946
TI  - Development of a computerized morphometry application for assessment of the tumor
      fraction in colon carcinoma tissue samples.
AB  - Determining the fraction of tumor cells in colon carcinoma samples analyzed for
      KRAS mutation status is important for choosing the proper testing modality and
      accurately interpreting the results. However, when asked to determine the tumor
      cell fraction in tissue samples, different pathologists give considerably
      different estimations, possibly leading to erroneous interpretation of KRAS
      mutation analysis results and poor treatment choices. To address this issue, we
      developed a free, easy-to-use computer program that estimates the tumor cell
      fraction on colon carcinoma slides that are immune-stained with anti-cytokeratin
      antibody. The program differentiates between the tumor area and the surrounding
      stroma on the basis of the immunostaining. Sixty such samples were evaluated by
      the program. In addition, the actual tumor cell fraction in these samples was
      measured. The tumor cell fraction estimated by the computer program showed a
      highly significant correlation with the actual measurements (R=0.64, P<0.001). In
      addition, we found that a short calibration step before beginning the computer
      estimation increased the accuracy of the results. In 4 cases (7%), there was some
      discrepancy between the computer estimation and the actual measurements; however,
      this was attributed to lower-quality immunohistochemical staining, indicating the
      importance of this phase in the analysis. In conclusion, we believe that this
      program can be used for standardizing the evaluation of the tumor cell fraction
      in colon carcinoma and that its use might aid in making better diagnosis and
      treatment choices for these patients.

PMID- 22595947
TI  - Identification of NPMc+ acute myeloid leukemia in bone marrow smears.
AB  - The most frequent genetic change currently known in acute myeloid leukemia (AML)
      is the mutation of the nucleophosmin (NPM) gene. Aberrant cytoplasmic
      accumulation of NPM protein (NPMc+) is the result of this mutation, and it can be
      demonstrated by immunohistochemistry for the identification of a favorable
      subgroup within "AML with normal karyotype" according to the World Health
      Organization classification. NPM staining pattern was defined in 71 AML and 15
      control cases by the use of bone marrow smears in order to overcome limitations
      observed due to immunohistochemistry. In 13/71 cases (18.3%), clear cytoplasmic
      staining of the leukemic blast cells was detectable that was comparable with the
      positivity of mitotic figures physiologically lacking nuclear membrane. The
      biological and genetic characteristics of the NPMc+ cases determined this way
      were identical with the previously published results including low CD34 and HLA
      DR expression and lack of recurrent karyotype abnormalities. Bone marrow smears
      are well applicable and therefore a real alternative for the determination of NPM
      with the highest accuracy for optimal risk stratification in AML.

PMID- 22595948
TI  - PAX8 mouse monoclonal antibody [BC12] recognizes a restricted epitope and is
      highly sensitive in renal cell and ovarian cancers but does not cross-react with
      b cells and tumors of pancreatic origin.
AB  - PAX8 is expressed in a high percentage of renal cell and ovarian cancers;
      however, the current existing anti-PAX8 rabbit polyclonal (P) antibodies also
      recognize B cells, pancreatic cancers, carcinoids, and some soft tissue tumors.
      Cross-reactivity with B cells can be especially troublesome in lymph nodes when
      identifying tumors of unknown origin. A new mouse monoclonal (M) anti-PAX8
      antibody (Clone BC12) has been developed that recognizes PAX8 expression in a
      high percentage of renal cell and ovarian carcinomas, whereas exhibiting no
      staining of B cells. PAX8 (M) was tested for specificity and sensitivity in over
      1300 cases of both normal and neoplastic tissues. PAX8 (M) demonstrated superior
      staining sensitivity in clear cell and papillary renal cell carcinomas (88.8% vs.
      84.4%) and in serous and endometrioid ovarian carcinomas (87% vs. 83%), when
      compared with PAX8 (P). PAX8 (M) also stained a high percentage of endometrial
      and thyroid cancers, 67.5% and 60.7%, respectively. PAX8 (M) demonstrated low
      sensitivity in cervical and bladder cancers, 2.5% and 1.4%, respectively. All
      other cancers including lung, breast, prostate, stomach, liver, soft tissue,
      pancreas, testis, brain, colon, melanoma, lymphoma, adrenal, pituitary, and
      rectal were negative. In normal tissue, PAX8 (P) stained lymph nodes, pancreas,
      and neuroendocrine cells of stomach and colon. In contrast, PAX8 (M) was negative
      in each of these tissues. These results demonstrate that mouse monoclonal PAX8
      [BC12] stains nuclei exclusively and performs well in formalin-fixed paraffin
      embedded tissues. PAX8 (M) is a highly sensitive marker for thyroid, renal, and
      ovarian cancers. Importantly, PAX8 (M) does not stain B cells and does not seem
      to recognize epitopes of pancreatic origin and neuroendocrine cells in stomach
      and colon; thus, providing superior specificity and making PAX8 [BC12] an
      excellent marker for confirming primary tumor site and for differential
      diagnosis.

PMID- 22595949
TI  - Demonstration of CDX2 is highly antibody dependant.
AB  - OBJECTS: CDX2 is a widely used immunohistochemical marker for intestinal
      differentiation in neoplasms. In the Nordic Immunohistochemical Quality Control
      external quality assessment scheme, only 45% of the laboratories participating in
      the CDX2 challenge in 2009 produced sufficient staining. A major cause of
      insufficient staining results appeared to be less successful primary antibody
      (Ab) clones. To evaluate the Ab performance in a standardized way, a comparative
      study was carried out. MATERIALS AND METHODS: Tissue microarrays containing 309
      non-neoplastic tissues and tumor samples with expected high, low, and no CDX2
      expression were used. Five Abs were selected for comparison: EPR2764Y
      concentrated (Conc), EPR2764Y in a ready-to-use format, and DAK-CDX2, AMT28, and
      CDX2-88, all Conc. The CDX2 stains were scored blindly using the H-score method.
      Tissue/tumor samples with a maximum H-score of 150 to 300 (on the basis of the
      staining giving the highest score) were classified as CDX2 high expressors,
      samples with a maximum H-score of 10 to 149 as low expressors, and samples with a
      maximum H-score <10 as negative. RESULTS AND CONCLUSIONS: A total of 106 tumors
      were CDX2 positive with at least one of the Abs. For 56 high-expressor tumors,
      the mean H-scores with EPR2764Y Conc, EPR2764Y ready-to-use, DAK-CDX2, AMT28, and
      CDX2-88 were 262, 236, 234, 167, and 149, respectively, and the percentage of
      positive tumors 100, 100, 100, 98, and 93, respectively. For 50 low-expressor
      tumors, the mean H-scores with the same Abs were 59, 26, 28, 7, and 5,
      respectively, and the percentage of positive tumors 98, 58, 64, 18, and 14,
      respectively. With EPR2764Y Conc, CDX2 was demonstrated in 5/19 (26%) urothelial
      carcinomas, 7/64 (11%) lung adenocarcinomas, 5/30 (17%) large cell/sarcomatoid
      lung carcinomas, and 4/19 (21%) esophagus squamous cell carcinomas. In-house
      optimized protocols gave for all 4 Conc Abs better staining results than the
      vendors' recommended protocols. The sensitivity of CDX2 Abs and protocols must be
      taken into consideration when classifying neoplasms of unknown origin.

PMID- 22595950
TI  - Follicular and mantle cell lymphoma characteristics present simultaneously in the
      same lymph node.
AB  - Follicular lymphoma is composed of clonal germinal center B cells. It shows a
      follicular pattern lacking mantle zones, with a network of interfollicular
      dendritic cells. Transformation to more aggressive lymphomas is documented, but
      the only connections to mantle cell lymphoma are described cases of composite
      lymphoma consisting of these 2 entities. We discuss here a case of a lymph node
      harboring CD20, CD10, BCL2, BCL6, cyclin D1, CD5, Ki67, and SOX11 with CD21,
      showing an almost intact network of dendritic cells in one part of a lymph node,
      and CD20, CD5, SOX11, BCL6, cyclin D1, CD10, Ki67, and CD21 cells restricted to
      the mantle area in another part of the same lymph node. Both parts of the lymph
      node had BCL2 rearrangement, a lack of t(11:14)(q13;q32), the presence of SOX11
      expression, and the same clonal band. The described case suggests heterogenous
      development of small cell lymphomas and indicates the possibility of
      differentiation regression. 

PMID- 22595951
TI  - Role of integrins in the carcinogenesis of squamous cell carcinoma of the tongue
      and lower lip.
AB  - OBJECTIVE AND METHODS: This study analyzed the distribution, intensity, and
      pattern of immunohistochemical expression of alpha2beta1, alpha3beta1, and
      alpha5beta1 integrins in squamous cell carcinoma (SCC) of the lower lip and
      tongue to identify biomarkers that reflect the clinical course of this cancer.
      Immunoexpression was compared considering prognostic parameters such as anatomic
      site, metastasis, and histologic grade of malignancy. RESULTS:
      Immunohistochemical analysis at the invasion front showed a predominance of
      granular cytoplasmic expression of the integrins studied. In most cases,
      immunopositive cells were diffusely distributed in the tumors, irrespective of
      their location, except for alpha3beta1 integrin-positive cells which were focally
      distributed in 53.3% of tongue SCC cases. With respect to staining intensity,
      positive staining for alpha2beta1 integrin was observed in 80% of lower lip SCCs
      and in 93.3% of tongue SCCs. Staining for alpha3beta1 integrin was moderately
      positive in 60% of lower lip and tongue SCCs. The staining intensity of
      alpha5beta1 integrin was moderately and strongly positive in 53.3% and 46.7% of
      lower lip SCCs, respectively, and in 46.7% and 53.3% of tongue SCCs. CONCLUSIONS:
      The strong immunoreactivity for integrins alpha2beta1, alpha3beta1, and
      alpha5beta1 seen in the oral SCC cases studied suggests a significant
      participation of these proteins in oral carcinogenesis. However, their expression
      does not reflect the clinical course of this cancer.

PMID- 22595952
TI  - Fabrication and investigation of gas sensing properties of Nb-doped TiO(2)
      nanotubular arrays.
AB  - Synthesis of Nb-containing titania nanotubular arrays at room temperature by
      electrochemical anodization is reported. Crystallization of pure and Nb-doped
      TiO(2) nanotubes was carried out by post-growth annealing at 400 degrees C. The
      morphology of the tubes obtained was characterized by scanning electron
      microscopy (SEM). Crystal structure and composition of tubes were investigated by
      glancing incidence x-ray diffraction (GIXRD) and total reflection x-ray
      fluorescence (TXRF). For the first time gas sensing characteristics of Nb-doped
      TiO(2) nanotubes were investigated and compared to those of undoped nanotubes.
      The functional properties of nanotubular arrays towards CO, H(2), NO(2), ethanol
      and acetone were tested in a wide range of operating temperature. The
      introduction of Nb largely improves conductivity and enhances gas sensing
      performances of TiO(2) nanotubes.

PMID- 22595953
TI  - On the heterogeneity of fluorescence lifetime of room temperature ionic liquids:
      onset of a journey for exploring red emitting dyes.
AB  - An excitation and emission wavelength dependent non-exponential fluorescence
      decay behaviour of room temperature ionic liquids (RTILs) has been noted. Average
      fluorescence lifetimes have been found to vary by a factor of three or more. Red
      emitting dyes dissolved in RTILs are found to follow hitherto unobserved single
      exponential fluorescence decay behaviour.

PMID- 22595954
TI  - Theoretical analysis of cooperative effects of small molecule activation by
      frustrated Lewis pairs.
AB  - The energy profiles of the activation reaction of small molecules (H(2), Br(2)
      and CO(2)) with boron/phosphorus frustrated Lewis pairs (FLPs) have been
      calculated with dispersion corrected DFT (TPSS-D3). We have investigated the
      cooperative nature of the reactions by analyzing interaction energies in the
      ternary system and for reactant pairs. The non-additive contributions to the
      total interaction energy add to the driving force of the activation reaction,
      even at early stages of the process. We propose the isosurface representation of
      the many-body deformation density Deltarho(mb) as a qualitative tool to visualize
      cooperative, non-additive effects in complex chemical systems.

PMID- 22595955
TI  - Short sleep duration and increased risk of hypertension:  a primary care medicine
      investigation.
AB  - OBJECTIVES: Compelling evidence from laboratory-based and population-based
      studies link sleep loss to negative cardiovascular health outcomes. However,
      little is known about the association between sleep duration and hypertension in
      primary care health settings, independently of other well controlled clinical and
      biochemical characteristics. We investigated the association between sleep
      duration and the prevalence of hypertension adjusting for 21 potential
      confounding factors in a noncontrolled primary care sample. METHODS: The sample
      included 1046 French adults older than 40 years (mean age, 55.5 years), who
      visited any of the general practitioners of primary care centers in the Paris
      area. Blood pressure (BP) readings, blood samples and standardized health and
      sleep questionnaires were performed on each participant. Hypertension inclusion
      criteria were either high BP measurements (SBP >= 140 mmHg or DBP >= 90 mmHg) or
      the use of antihypertensive medications. Sleep duration was recorded as the self
      reported average number of hours of sleep per night during the week. Logistic
      regressions were performed to test the association between hypertension and sleep
      duration adjusted for sociodemographic, clinical, biochemical, lifestyle,
      psychological and sleep disorder covariates. RESULTS: Compared to the group
      sleeping 7 h, individuals sleeping 5 h or less had an increased odds ratio (OR)
      for the prevalence of hypertension [OR = 1.80, 95% confidence interval (1.06
      3.05)], after adjusting for 21 potential confounders which did not markedly
      attenuate this association. CONCLUSION: Our data provide further epidemiologic
      evidence that with no specific selection in primary care medicine, usual short
      sleep duration increases the risk of hypertension prevalence in adults over 40
      years.

PMID- 22595956
TI  - Summer does not always mean lower: seasonality of 24 h, daytime, and night-time
      blood pressure.
AB  - OBJECTIVE: Evaluation of seasonal influences on ambulatory blood pressure
      monitoring (ABPM) values in a very large population living in a mild-climate
      geographic area. METHODS: Among patients referred to our Hypertension Center
      between September 2002 and January 2011 with a reliable ABPM, we considered those
      in the two hottest (July and August) vs. those in the two coldest (January and
      February) months. RESULTS: Seven hundred and forty-two men (53.2%) and 653 women
      (46.8%) were studied; 1245 (89.3%) were hypertensive patients of which 795
      (63.9%) were drug-treated. In winter, mean daytime SBP and DBP were higher (P =
      0.001 and P < 0.001, respectively), but only 24-h DBP was significantly higher (P
      = 0.012). On the contrary, higher night-time SBP and pulse pressure were recorded
      in summer (P = 0.005 and P = 0.023, respectively). Uncontrolled hypertensive
      patients had the highest mean difference between winter and summer night-time SBP
      (127.1 +/- 13.4 vs. 131.0 +/- 12.6 mmHg; P = 0.001). In winter a dipping pattern
      was prevalent (58.2%), whereas in summer a nondipping pattern prevailed (61.9%; P
      < 0.001). Isolated nocturnal hypertension (INH) was present in 9.8% in winter vs.
      15.2% in summer (P = 0.003). CONCLUSION: Our data on a very large ABPM sample
      confirmed that hottest summer months are associated with lower daytime BP and
      also lower 24-h DBP. However, we found an inverse relationship regarding night
      time BP, dipping pattern, and INH that were higher or more common in summer.
      These findings were even more evident in treated patients, especially when not at
      target. Different sleeping behaviors or improper dose reduction of drug therapy
      in summer may explain the findings.

PMID- 22595957
TI  - Vitamin D status partly explains ethnic differences in blood pressure:  the
      'Surinamese in the Netherlands:  study on ethnicity and health'.
AB  - OBJECTIVE: To investigate the role of vitamin D in explaining ethnic differences
      in blood pressure among three ethnic groups in the Netherlands (ethnic Dutch,
      African Surinamese, and south Asian Surinamese). METHODS: Data were derived from
      the 'Surinamese in the Netherlands: study on ethnicity and health' study, a
      population-based observational study. We included 1420 participants (505 ethnic
      Dutch, 330 south Asian Surinamese, and 585 African Surinamese), aged 35-60 years,
      in whom serum vitamin D (25-hydroxyvitamin D) and SBP and DBP were measured. Data
      were analyzed by using linear (SBP, DBP) and logistic (hypertension) regression
      analyses, using ethnicity as independent variable and adjusting for potential
      confounders. To study the impact of vitamin D, we additionally adjusted for
      vitamin D in a final model. RESULTS: South Asian Surinamese had a 5.6 mmHg higher
      SBP and 4.9 mmHg higher DBP as compared with the Dutch after adjustment for age,
      sex, season, physical activity, smoking, education, and BMI. Further adjustment
      for vitamin D explained 14 and 6% of these SBP and DBP differences, respectively.
      African Surinamese had an 8.9 mmHg higher SBP and 6.8 mmHg higher DBP as compared
      with the Dutch. Variation in vitamin D explained 7 and 4% of these SBP and DBP
      differences. South Asian Surinamese and African Surinamese had 2.2 (1.5-3.2) and
      3.3 (2.4-4.6) times higher odds of having hypertension compared with ethnic
      Dutch. Vitamin D explained 25 and 17% of the variations in SBP and DBP,
      respectively, resulting in odds ratio of 1.9 (1.3-2.9) and 2.9 (2.0-4.3),
      respectively. CONCLUSION: Higher blood pressures and higher hypertension risk in
      south Asian Surinamese and African Surinamese were partly explained by their
      poorer vitamin D status. However, even after adjustment, significant ethnic blood
      pressure differences persisted.

PMID- 22595958
TI  - Plasma renin activity and the aldosterone-to-renin ratio are associated with the
      development of chronic kidney disease:  the Ohasama Study.
AB  - BACKGROUND: The aldosterone-to-renin ratio (ARR) is used to screen for primary
      aldosteronism and could be an index for salt sensitivity. The association between
      ARR and the development of chronic kidney disease (CKD) is completely unknown.
      METHOD: A longitudinal observational study involving 689 participants from a
      general Japanese population (mean age 58.2 years; 68.5% women) who did not have
      CKD and were not receiving antihypertensive medication at baseline was conducted.
      The estimated glomerular filtration rate (eGFR) was calculated from serum
      creatinine levels, and CKD was defined as eGFR less than 60 ml/min per 1.73 m(2)
      and/or dipstick-positive proteinuria. The associations of baseline plasma renin
      activity (PRA), plasma aldosterone concentration, and ARR with the development of
      CKD were examined using Cox proportional hazard regression analysis adjusted for
      sex, age, BMI, smoking, drinking, history of hypercholesterolemia, diabetes
      mellitus, and cardiovascular disease, SBP, and baseline eGFR. RESULTS: During a
      mean 9.1-year follow-up, 118 participants developed CKD. A 1 standard deviation
      increment in the natural log-transformed (ln) ARR was positively associated with
      the incidence of CKD (hazard ratio 1.29, P = 0.012). LnPRA showed an inverse
      association (hazard ratio 0.76, P = 0.007). Meanwhile, plasma aldosterone
      concentration was not associated with CKD. Individuals who developed CKD had
      significantly lower baseline PRA (0.97 vs. 1.14 ng/ml per h; P = 0.03) and higher
      baseline ARR levels [66.6 vs. 56.8 (pg/ml)/(ng/ml per h); P = 0.02] than those
      who did not. CONCLUSIONS: Lower PRA and higher ARR were associated with the
      development of CKD in a general population, suggesting that they are independent
      predictors of CKD.

PMID- 22595959
TI  - Conductance fluctuations in gold point contacts: an atomistic picture.
AB  - This paper concerns an experimental and theoretical study of the transition
      between two consecutive conductance plateaus as obtained in breaking gold contact
      experiments. The experimental measurements performed at 100 K with a scanning
      tunneling microscope and variable elongation speeds show that the transitions
      between consecutive plateaus can appear in the conductance traces as an abrupt
      conductance step, a smooth quasicontinuous change or as large amplitude
      conductance fluctuations. The theoretical calculations based on a non-orthogonal
      tight-binding Hamiltonian have shown that for a given deformation there are
      several structures having close and competing energies.We discuss the relation
      between the temperature, sampling frequency, stretching speed and energy barriers
      which can explain the conditions for the observation of the three kinds of
      conductance traces.

PMID- 22595960
TI  - C-type natriuretic peptide stimulates ovarian follicle development.
AB  - C-type natriuretic peptide (CNP) encoded by the NPPC (Natriuretic Peptide
      Precursor C) gene expressed in ovarian granulosa cells inhibits oocyte maturation
      by activating the natriuretic peptide receptor (NPR)B (NPRB) in cumulus cells. RT
      PCR analyses indicated increased NPPC and NPRB expression during ovarian
      development and follicle growth, associated with increases in ovarian CNP
      peptides in mice. In cultured somatic cells from infantile ovaries and granulosa
      cells from prepubertal animals, treatment with CNP stimulated cGMP production.
      Also, treatment of cultured preantral follicles with CNP stimulated follicle
      growth whereas treatment of cultured ovarian explants from infantile mice with
      CNP, similar to FSH, increased ovarian weight gain that was associated with the
      development of primary and early secondary follicles to the late secondary stage.
      Of interest, treatment with FSH increased levels of NPPC, but not NPRB,
      transcripts in ovarian explants. In vivo studies further indicated that daily
      injections of infantile mice with CNP for 4 d promoted ovarian growth, allowing
      successful ovulation induction by gonadotropins. In prepubertal mice, CNP
      treatment alone also promoted early antral follicle growth to the preovulatory
      stage, leading to efficient ovulation induction by LH/human chorionic
      gonadotropin. Mature oocytes retrieved after CNP treatment could be fertilized in
      vitro and developed into blastocysts, allowing the delivery of viable offspring.
      Thus, CNP secreted by growing follicles is capable of stimulating preantral and
      antral follicle growth. In place of FSH, CNP treatment could provide an
      alternative therapy for female infertility.

PMID- 22595962
TI  - Porphyrin-based multi-signal chemosensors for Pb2+ and Cu2+.
AB  - Two metal-free tetra(aryl)porphyrin derivatives modified by one and four N,N
      bis(2-pyridylmethyl)amino group(s), namely porphyrin-1-DPA (1) and porphyrin-4
      DPA (2) respectively, have been designed, synthesized, and characterized. Binding
      with Pb(2+) induces a significant change in their solution color and in the ratio
      of two absorption/fluorescence signal peaks, rendering them the first example of
      porphyrin-based triple-signal optical sensors for Pb(2+). Their dual-mode Cu(2+)
      selective sensing properties via either the porphyrin fluorescence ON-OFF
      mechanism or metal displacement from the 1-Pb(2+) complex that results in a
      triple-signal change clearly reveals their potential application as excellent and
      versatile sensors.

PMID- 22595961
TI  - Rescue of misrouted GnRHR mutants reveals its constitutive activity.
AB  - G protein-coupled receptors (GPCR) play central roles in almost all physiological
      functions, and mutations in GPCR are responsible for over 30 hereditary diseases
      associated with loss or gain of receptor function. Gain of function mutants are
      frequently described as having constitutive activity (CA), that is, they activate
      effectors in the absence of agonist occupancy. Although many GPCR have mutants
      with CA, the GnRH receptor (GnRHR) was not, until 2010, associated with any CA
      mutants. The explanation for the failure to observe CA appears to be that the
      quality control system of the cell recognizes CA mutants of GnRHR as misfolded
      and retains them in the endoplasmic reticulum. In the present study, we
      identified several human (h)GnRHR mutants with substitutions in transmembrane
      helix 6 (F(272)K, F(272)Q, Y(284)F, C(279)A, and C(279)S) that demonstrate
      varying levels of CA after being rescued by pharmacoperones from different
      chemical classes and/or deletion of residue K(191), a modification that increases
      trafficking to the plasma membrane. The movement of the mutants from the
      endoplasmic reticulum (unrescued) to the plasma membrane (after rescue) is
      supported by confocal microscopy. Judging from the receptor-stimulated inositol
      phosphate production, mutants F(272)K and F(272)Q, after rescue, display the
      largest level of CA, an amount that is comparable with agonist-stimulated
      activation. Because mutations in other GPCR are, like the hGnRHR, scrutinized by
      the quality control system, this general approach may reveal CA in receptor
      mutants from other systems. A computer model of the hGnRHR and these mutants was
      used to evaluate the conformation associated with CA.

PMID- 22595964
TI  - Risk of stillbirth at extremes of birth weight between 20 to 41 weeks gestation.
AB  - OBJECTIVE: To determine the risk of stillbirth between 20 to 41 weeks gestation,
      at highly detailed weight percentiles, including extreme degrees of small (SGA)
      and large (LGA) for gestational age birth weight. STUDY DESIGN: We completed a
      population-based study of all births in Ontario, Canada between 2002 and 2007. We
      included 767, 016 liveborn and 4,697 stillborn singletons delivered between 20
      and 41 weeks gestation. Smoothed birthweight percentile curves were generated for
      males and females, combining livebirths and stillbirths. Quantile regression was
      used to calculate sex-specific absolute birthweight differences and 95%
      confidence intervals (CI) between stillborns vs liveborns at various gestational
      ages. Logistic regression was used to calculate the odds ratios (OR) for
      stillbirth at various sex-specific birthweight percentiles, including <1st and >=
      99th percentile. OR were adjusted for maternal age and parity. RESULT: At the
      10th percentile, stillborns weighed significantly less than liveborns starting at
      24 weeks gestation. By 32 weeks, this difference was 590 g (95% CI 430 to 750)
      for males and 551 g (95% CI 345 to 448) for females. A reverse J-shaped
      association was observed between birthweight percentile and risk of stillbirth
      across all gestational ages. Relative to the 40th to 60th percentile referent,
      the adjusted OR for stillbirth was 9.63 (95% CI 8.39 to 11.06) at a birth weight
      <1st percentile. At >= 99th percentile, the adjusted OR was 2.24 (95% CI 1.76 to
      2.86). The risk of stillbirth at extreme birthweight percentiles was robustly
      observed across gestational ages. CONCLUSION: Substantial birthweight differences
      exist between stillborns and newborns. As a possible hallmark of impending
      intrauterine death, severe SGA and LGA may each be potential targets for future
      stillbirth prevention initiatives.

PMID- 22595965
TI  - Prenatal alcohol exposure, blood alcohol concentrations and alcohol elimination
      rates for the mother, fetus and newborn.
AB  - Fetal alcohol spectrum disorders (FASDs) are a common cause of intellectual
      impairment and birth defects. More recently, prenatal alcohol exposure (PAE) has
      been found to be a risk factor for fetal mortality, stillbirth and infant and
      child mortality. This has led to increased concern about detection and management
      of PAE. One to 2 h after maternal ingestion, fetal blood alcohol concentrations
      (BACs) reach levels nearly equivalent to maternal levels. Ethanol elimination by
      the fetus is impaired because of reduced metabolic capacity. Fetal exposure time
      is prolonged owing to the reuptake of amniotic-fluid containing ethanol by the
      fetus. Alcohol elimination from the fetus relies on the mother's metabolic
      capacity. Metabolic capacity among pregnant women varies eightfold (from 0.0025
      to 0.02 g dl(-1)  h(-1)), which may help explain how similar amounts of ethanol
      consumption during pregnancy results in widely varying phenotypic presentations
      of FASD. At birth physiological changes alter the neonate's metabolic capacity
      and it rapidly rises to a mean value of 83.5% of the mother's capacity. FASDs are
      highly recurrent and younger siblings have increased risk. Detection of prenatal
      alcohol use offers an important opportunity for office-based interventions to
      decrease exposure for the remainder of pregnancy and identification of women who
      need substance abuse treatment. Mothers of children with FAS have been found to
      drink faster, get drunk quicker and to have higher BACs. A modest increase in the
      prevalence of a polymorphism of alcohol dehydrogenase, which increases
      susceptibility to adverse outcomes from PAE has been reported. Lastly, detection
      of alcohol use and appropriate management would decrease risk from PAE for
      subsequent pregnancies.

PMID- 22595966
TI  - A robust, high-sensitivity stealth probe for peptidases.
AB  - A robust, modular fluorogenic probe system has been developed which allows the
      highly sensitive off-ON detection of aminopeptidase activity by releasing an
      exceptionally photostable, insoluble, phenolic ESIPT fluorophore. The probes
      generate no false positive signal in over 24 hours, but when activated give a
      signal within 10 minutes.

PMID- 22595967
TI  - Hydrolysis of DNA model substrates catalyzed by metal-substituted Wells-Dawson
      polyoxometalates.
AB  - In this study we report the first example of phosphoester bond hydrolysis in 4
      nitrophenyl phosphate (NPP) and bis-4-nitrophenyl phosphate (BNPP), two commonly
      used DNA model substrates, promoted by metal-substituted polyoxometalates (POMs).
      Different transition metal and lanthanide ions were incorporated into the Wells
      Dawson polyoxometalate framework and subsequently screened for their hydrolytic
      activity towards the cleavage of the phosphoester bonds in NPP and BNPP. From
      these complexes, the Zr(iv)-substituted POM showed the highest reactivity. At pD
      7.2 and 50  degrees C a NPP hydrolysis rate constant of 7.71 * 10(-4) min(-1)
      (t(1/2) = 15 h) was calculated, representing a rate enhancement of nearly two
      orders of magnitude in comparison with the spontaneous hydrolysis of NPP. The
      catalytic (k(c) = 1.73 * 10(-3) min(-1)) and formation constant (K(f) = 520.02 M(
      1)) for the NPP-Zr(iv)-POM complex were determined from kinetic experiments. The
      reaction proceeded faster in acidic conditions and (31)P NMR experiments showed
      that faster hydrolysis is proportional to the presence of the 1 : 1
      monosubstituted Zr(iv)-POM at acidic pD values. The strong interaction of the 1 :
      1 monosubstituted Zr(iv)-POM with the P-O bond of NPP was evidenced by the large
      chemical shift and the line broadening of the (31)P nucleus in NPP observed upon
      addition of the metal complex. Significantly, a ten-fold excess of NPP was fully
      hydrolyzed in the presence of the Zr(iv)-POM, proving the principles of
      catalysis. The NMR spectra did not show sign of any paramagnetic species,
      excluding an oxidative cleavage mechanism and suggesting purely hydrolytic
      cleavage.

PMID- 22595968
TI  - Somatic instability of the expanded CTG triplet repeat in myotonic dystrophy type
      1 is a heritable quantitative trait and modifier of disease severity.
AB  - Deciphering the contribution of genetic instability in somatic cells is critical
      to our understanding of many human disorders. Myotonic dystrophy type 1 (DM1) is
      one such disorder that is caused by the expansion of a CTG repeat that shows
      extremely high levels of somatic instability. This somatic instability has
      compromised attempts to measure intergenerational repeat dynamics and infer
      genotype-phenotype relationships. Using single-molecule PCR, we have
      characterized more than 17 000 de novo somatic mutations from a large cohort of
      DM1 patients. These data reveal that the estimated progenitor allele length is
      the major modifier of age of onset. We find no evidence for a threshold above
      which repeat length does not contribute toward age at onset, suggesting
      pathogenesis is not constrained to a simple molecular switch such as nuclear
      retention of the DMPK transcript or haploinsufficiency for DMPK and/or SIX5.
      Importantly, we also show that age at onset is further modified by the level of
      somatic instability; patients in whom the repeat expands more rapidly, develop
      the symptoms earlier. These data establish a primary role for somatic instability
      in DM1 severity, further highlighting it as a therapeutic target. In addition, we
      show that the level of instability is highly heritable, implying a role for
      individual-specific trans-acting genetic modifiers. Identifying these trans
      acting genetic modifiers will facilitate the formulation of novel therapies that
      curtail the accumulation of somatic expansions and may provide clues to the role
      these factors play in the development of cancer, aging and inherited disease in
      the general population.

PMID- 22595970
TI  - Identification of cis-regulatory variation influencing protein abundance levels
      in human plasma.
AB  - Proteins are central to almost all cellular processes, and dysregulation of
      expression and function is associated with a range of disorders. A number of
      studies in human have recently shown that genetic factors significantly
      contribute gene expression variation. In contrast, very little is known about the
      genetic basis of variation in protein abundance in man. Here, we assayed the
      abundance levels of proteins in plasma from 96 elderly Europeans using a new
      aptamer-based proteomic technology and performed genome-wide local (cis-)
      regulatory association analysis to identify protein quantitative trait loci
      (pQTL). We detected robust cis-associations for 60 proteins at a false discovery
      rate of 5%. The most highly significant single nucleotide polymorphism detected
      was rs7021589 (false discovery rate, 2.5 * 10(-12)), mapped within the gene
      coding sequence of Tenascin C (TNC). Importantly, we identified evidence of cis
      regulatory variation for 20 previously disease-associated genes encoding protein,
      including variants with strong evidence of disease association show significant
      association with protein abundance levels. These results demonstrate that common
      genetic variants contribute to the differences in protein abundance levels in
      human plasma. Identification of pQTLs will significantly enhance our ability to
      discover and comprehend the biological and functional consequences of loci
      identified from genome-wide association study of complex traits. This is the
      first large-scale genetic association study of proteins in plasma measured using
      a novel, highly multiplexed slow off-rate modified aptamer (SOMAmer) proteomic
      platform.

PMID- 22595969
TI  - Novel association approach for variable number tandem repeats (VNTRs) identifies
      DOCK5 as a susceptibility gene for severe obesity.
AB  - Variable number tandem repeats (VNTRs) constitute a relatively under-examined
      class of genomic variants in the context of complex disease because of their
      sequence complexity and the challenges in assaying them. Recent large-scale
      genome-wide copy number variant mapping and association efforts have highlighted
      the need for improved methodology for association studies using these complex
      polymorphisms. Here we describe the in-depth investigation of a complex region on
      chromosome 8p21.2 encompassing the dedicator of cytokinesis 5 (DOCK5) gene. The
      region includes two VNTRs of complex sequence composition which flank a common
      3975 bp deletion, all three of which were genotyped by polymerase chain reaction
      and fragment analysis in a total of 2744 subjects. We have developed a novel VNTR
      association method named VNTRtest, suitable for association analysis of multi
      allelic loci with binary and quantitative outcomes, and have used this approach
      to show significant association of the DOCK5 VNTRs with childhood and adult
      severe obesity (P(empirical)= 8.9 * 10(-8) and P= 3.1 * 10(-3), respectively)
      which we estimate explains ~0.8% of the phenotypic variance. We also identified
      an independent association between the 3975 base pair (bp) deletion and obesity,
      explaining a further 0.46% of the variance (P(combined)= 1.6 * 10(-3)). Evidence
      for association between DOCK5 transcript levels and the 3975 bp deletion (P=
      0.027) and both VNTRs (P(empirical)= 0.015) was also identified in adipose tissue
      from a Swedish family sample, providing support for a functional effect of the
      DOCK5 deletion and VNTRs. These findings highlight the potential role of DOCK5 in
      human obesity and illustrate a novel approach for analysis of the contribution of
      VNTRs to disease susceptibility through association studies.

PMID- 22595971
TI  - Vitamin D receptor binding, chromatin states and association with multiple
      sclerosis.
AB  - Both genetic and environmental factors contribute to the aetiology of multiple
      sclerosis (MS). More than 50 genomic regions have been associated with MS
      susceptibility and vitamin D status also influences the risk of this complex
      disease. However, how these factors interact in disease causation is unclear. We
      aimed to investigate the relationship between vitamin D receptor (VDR) binding in
      lymphoblastoid cell lines (LCLs), chromatin states in LCLs and MS-associated
      genomic regions. Using the Genomic Hyperbrowser, we found that VDR-binding
      regions overlapped with active regulatory regions [active promoter (AP) and
      strong enhancer (SE)] in LCLs more than expected by chance [45.3-fold enrichment
      for SE (P < 2.0e-05) and 63.41-fold enrichment for AP (P < 2.0e-05)].
      Approximately 77% of VDR regions were covered by either AP or SE elements. The
      overlap between VDR binding and regulatory elements was significantly greater in
      LCLs than in non-immune cells (P < 2.0e-05). VDR binding also occurred within MS
      regions more than expected by chance (3.7-fold enrichment, P < 2.0e-05).
      Furthermore, regions of joint overlap SE-VDR and AP-VDR were even more enriched
      within MS regions and near to several disease-associated genes. These findings
      provide relevant insights into how vitamin D influences the immune system and the
      risk of MS through VDR interactions with the chromatin state inside MS regions.
      Furthermore, the data provide additional evidence for an important role played by
      B cells in MS. Further analyses in other immune cell types and functional studies
      are warranted to fully elucidate the role of vitamin D in the immune system.

PMID- 22595972
TI  - Mutant superoxide dismutase-1 indistinguishable from wild-type causes ALS.
AB  - A reason for screening amyotrophic lateral sclerosis (ALS) patients for mutations
      in the superoxide dismutase-1 (SOD1) gene is the opportunity to find novel
      mutations with properties that can give information on pathogenesis. A novel
      c.352C>G (L117V) SOD1 mutation was found in two Syrian ALS families living in
      Europe. The disease showed unusually low penetrance and slow progression. In
      erythrocytes, the total SOD1 activity, as well as specific activity of the mutant
      protein, was equal in carriers of the mutation and family controls lacking SOD1
      mutations. The structural stabilities of the L117V mutant and wild-type SOD1
      under denaturing conditions were likewise equal, but considerably lower than that
      of murine SOD1. As analyzed with an ELISA specific for misfolded SOD1 species, no
      differences were found in the content of misfolded SOD1 protein between extracts
      of fibroblasts from wild-type controls and from an L117V patient. In contrast,
      elevated levels of misfolded SOD1 protein were found in fibroblasts from ALS
      patients carrying seven other mutations in the SOD1 gene. We conclude that
      mutations in SOD1 that result in a fully stable protein are associated with low
      disease penetrance for ALS and may be found in cases of apparently sporadic ALS.
      Wild-type human SOD1 is moderately stable, and was found here to be within the
      stability range of ALS-causing SOD1 variants, lending support to the hypothesis
      that wild-type SOD1 could be more generally involved in ALS pathogenesis.

PMID- 22595973
TI  - Significant reduction in central venous catheter-related bloodstream infections
      in children on HPN after starting treatment with taurolidine line lock.
AB  - OBJECTIVE: The aim of this study was to review the incidence and type of central
      venous catheter-related bloodstream infection in children on treatment with home
      parenteral nutrition (PN) before and after the introduction of taurolidine.
      Taurolidine is a catheter lock solution that prevents biofilm formation and has
      broad-spectrum bactericidal and antifungal action. Its use in pediatric patients
      on PN has only been reported in case studies. METHODS: A total of 19 children
      were reviewed, with the diagnoses of enteropathy (8 cases), short bowel syndrome
      (7 cases), and gastrointestinal dysmotility (4 cases). Incidence and type of
      sepsis were reviewed for 8 to 12 months pre- (when heparin was used) and 2 to 33
      months postintroduction of the taurolidine catheter lock. RESULTS: There were 8.6
      episodes of catheter-related bloodstream infections per 1000 catheter days with
      heparin and 1.1 episodes per 1000 catheter days with taurolidine (P=0.002). A
      total of 14 of the 19 patients (74%) had no infections for up to 33 months after
      changing to taurolidine. No reports of multiresistant organisms or adverse
      effects with taurolidine were found. CONCLUSIONS: Taurolidine line lock was
      associated with a decreased incidence of catheter-related bloodstream infections.
      This finding supports its use in patients with a history of septicemia on
      treatment with cyclical PN.

PMID- 22595975
TI  - Photoluminescence in semiconductor nanoparticles: an atomistic view of excited
      state relaxation in nanosized ZnS.
AB  - We discuss how an approach that combines global optimisation and time-dependent
      density functional theory (TD-DFT) calculations allows one to predict the
      photoluminescence (PL) signature of true nanosized semiconductor nanoparticles.
      As a demonstration we calculate the PL signature of both bare and water covered
      zinc sulfide nanoparticles and demonstrate that we can successfully reproduce
      their experimentally measured PL signatures. Our TD-DFT calculations suggest that
      the excited state, after relaxation, becomes highly localised and that the degree
      of localisation changes with nanoparticle size. We also show that adsorbed water
      molecules can strongly influence the nanoparticle's final excited state minimum
      and PL signature. Finally, we discuss how this approach can be used to predict
      the effect of doping and what the next important methodological step will be on
      the route to theoretically understanding processes such as photocatalysis.

PMID- 22595974
TI  - Oral absorbable fat-soluble vitamin formulation in pediatric patients with
      cholestasis.
AB  - OBJECTIVE: Fat-soluble vitamin (FSV) deficiencies are common complications in
      pediatric patients with chronic cholestasis. The aim of the present study was to
      evaluate the status of FSV deficiencies in patients under present practice and to
      test the effect of an oral, absorbable, fat-soluble vitamin formulation (OAFSV)
      in these patients. METHODS: We recruited a total of 23 pediatric patients
      receiving conventional FSV supplementation in a single medical center, with
      diagnosis of biliary atresia (10), progressive familial intrahepatic cholestasis
      (9), Alagille syndrome (2), and other conditions (2). Ten patients switched to
      OAFSV and continued for 3 months. Plasma levels of vitamins A, D, and E and an
      international normalized ratio (INR) for prothrombin time (PT), a surrogate
      marker for vitamin K deficiency, were measured. RESULTS: The proportion of
      patients with FSV A, D, E, and K deficiencies under conventional supplementation
      was 73.9%, 81.8%, 91.3%, and 20.0%, respectively. In patients with total
      bilirubin levels >=3.0  mg/dL, the proportion of at least 1 FSV deficiency was
      100%; and the deficiency rates of vitamin A, D, E, and K were 78.6%, 100.0%,
      100.0% and 21.4%, respectively. Of the 10 patients receiving standard daily dose
      of OAFSV for 3 months, no adverse events or overdose effects were found. The
      rates of vitamin A, D, and E deficiency in the patients receiving OAFSV decreased
      from 80.0%, 100%, and 100%, respectively, to 70.0%, 60.0%, and 60.0% after 3
      months of oral supplementation. CONCLUSIONS: High rates of FSV deficiency were
      found in pediatric patients with chronic cholestasis under present follow-up.
      OAFSV supplementation is safe and potentially effective in pediatric patients
      with cholestasis.

PMID- 22595976
TI  - Synthesis of isoxazoles en route to semi-aromatized polyketides: dehydrogenation
      of benzonitrile oxide-para-quinone acetal cycloadducts.
AB  - A variety of highly functionalized polycyclic isoxazoles are prepared by a two
      step protocol: (1) 1,3-dipolar cycloaddition of o,o'-disubstituted benzonitrile
      oxides to para-quinone mono-acetals, then (2) dehydrogenation. The cycloaddition
      proceeds in a regioselective manner, favouring the formation of the 4-acyl
      cycloadducts, which are suitable intermediates for the synthesis of semi
      aromatized polycyclic targets derived from polyketide type-II biosynthesis.

PMID- 22595977
TI  - Water compatibility and organic transformations of organo-Zintl deltahedral
      clusters.
AB  - We report the remarkable stability of di-substituted organo-Zintl deltahedral
      clusters in the presence of water. This has been exploited in a reaction at the
      organic substituents of the cluster which produces water as a by-product. Also
      reported are the synthesis, characterization, and crystal structure of [K
      krypt](2)[Ge(9)-(CH=CH-CH(2)NH(2))(2)] involved in the reaction.

PMID- 22595978
TI  - Two solvent and temperature dependent copper(II) compounds formed by a flexible
      ligand: syntheses, structures and SC-SC transformation.
AB  - A nonporous neutral framework [CuCl(2)(m-bttmb)(2)](n) (1) was changed into a
      porous ionic {[Cu(m-bttmb)(2)(H(2)O)Cl]Cl(CH(3)CN)(0.5)(H(2)O)(2.75)}(n) (2) by
      simply increasing the amount of CH(3)CN in the mixed solvent (CH(3)CN and H(2)O)
      or temperature in the reactions of CuCl(2).2H(2)O with 1,3-bis(triazol-1
      ylmethyl)-2,4,6-trimethylbenzene (m-bttmb). 1 undergoes transformation into 2
      when treated with CH(3)CN. Both 1 and 2 have 2D 4-connected (4,4) network
      architectures but in different packing arrangements. These compounds have been
      characterized by single-crystal X-ray diffraction analysis, elemental analysis,
      IR spectra and thermogravimetric analysis. This work may provide a way to control
      the formation of neutral or ionic frameworks, as well as porosities by adjusting
      the polarity and components of the solvents.

PMID- 22595979
TI  - Is there an association between HOST grades and sperm quality?
AB  - BACKGROUND: Intracytoplasmic sperm injection (ICSI) is the primary treatment for
      male infertility. However for this procedure, with the exception of visual
      morphological selection, there is no standardization for sperm selection.
      Recently, the hypo-osmotic swelling test (HOST) has been proposed to potentially
      select sperm with intact membranes. The aim of this study is to evaluate the
      ability of this technique to select functional sperm in terms of apoptosis and
      morphology, as well as nuclear integrity. METHODS: A total of 20 semen samples
      were randomly collected from men who attended the Andrology Unit of the Isfahan
      Fertility and Infertility Center. Semen samples were washed and exposed to
      hypotonic conditions, before being fixed and simultaneously assessed for membrane
      integrity as well as abnormal morphology, DNA fragmentation and protamine
      deficiency by using Papanicolaou, TUNEL and CMA3 staining techniques,
      respectively. The remaining semen samples were washed with calcium buffer and
      stained by Annexin V, then exposed to hypotonic conditions before being assessed
      for early apoptosis along with membrane integrity. RESULTS: HOST grade 'd',
      followed by grade 'c', showed the highest percentages of healthy sperm, whereas
      sperm of HOST grade 'g' in which anomalies in terms of apoptosis, abnormal head
      morphology or nuclear immaturity or membrane damage, were most frequently
      observed in the samples assessed. CONCLUSIONS: Integration of HOST into the sperm
      selection procedure may provide a valuable tool for selection of functional sperm
      required for ICSI. According to this study, insemination of HOST grade 'g' sperm
      should be avoided during ICSI.

PMID- 22595981
TI  - Prevalence of allergy and upper respiratory tract symptoms in runners of the
      London marathon.
AB  - BACKGROUND: The prevalence of self-reported upper respiratory tract (URT)
      symptoms in athletes has been traditionally associated with opportunistic
      infection during the temporal suppression of immune function after prolonged
      exercise. There is little evidence for this, and a competing noninfectious
      hypothesis has been proposed, whereby the exercise-induced immune system
      modulations favor the development of atopy and allergic disease, which manifests
      as URT symptoms. The aim of this study was to examine the association between
      allergy and URT symptoms in runners after an endurance running event. METHODS:
      Two hundred eight runners from the 2010 London Marathon completed the validated
      Allergy Questionnaire for Athletes (AQUA) and had serum analyzed for total and
      specific immunoglobulin E response to common inhalant allergens. Participants who
      completed the marathon and nonrunning controls who lived in the same household
      were asked to complete a diary on URT symptoms. RESULTS: Forty percent of runners
      had allergy as defined by both a positive AQUA and elevated specific
      immunoglobulin E. Forty-seven percent of runners experienced URT symptoms after
      the marathon. A positive AQUA was a significant predictor of postmarathon URT
      symptoms in runners. Only 19% of nonrunning controls reported symptoms.
      CONCLUSIONS: The prevalence of allergy in recreational marathon runners was
      similar to that in elite athletes and higher than that in the general population.
      There was a strong association between a positive AQUA and URT symptoms. The low
      proportion of households in which both runners and nonrunners were symptomatic
      suggests that the nature of symptoms may be allergic or inflammatory based rather
      than infectious. Allergy is a treatable condition, and its potential effect on
      performance and health may be avoided by accurate clinical diagnosis and
      management. Both athletes' and coaches' awareness of the potential implications
      of poorly managed allergy needs to be raised.

PMID- 22595980
TI  - Adaptation and applications of a realistic digital phantom based on patient lung
      tumor trajectories.
AB  - Digital phantoms continue to play a significant role in modeling and
      characterizing medical imaging. The currently available XCAT phantom incorporates
      both the flexibility of mathematical phantoms and the realistic nature of
      voxelized phantoms. This phantom generates images based on a regular breathing
      pattern and can include arbitrary lung tumor trajectories. In this work, we
      present an algorithm that modifies the current XCAT phantom to generate 4D
      imaging data based on irregular breathing. First, a parameter is added to the
      existing XCAT phantom to include any arbitrary tumor motion. This modification
      introduces the desired tumor motion but, comes at the cost of decoupled
      diaphragm, chest wall and lung motion. To remedy this problem diaphragm and chest
      wall motion is first modified based on initial tumor location and then input to
      the XCAT phantom. This generates a phantom with synchronized respiratory motion.
      Mapping of tumor motion trajectories to diaphragm and chest wall motion is done
      by adaptively calculating a scale factor based on tumor to lung contour distance.
      The distance is calculated by projecting the initial tumor location to lung edge
      contours characterized by quadratic polynomials. Data from ten patients were used
      to evaluate the accuracy between actual independent tumor location and the
      location obtained from the modified XCAT phantom. The RMSE and standard
      deviations for ten patients in x, y, and z directions are: (0.29 +/- 0.04, 0.54
      +/- 0.17, and0.39 +/- 0.06) mm. To demonstrate the utility of the phantom, we use
      the new phantom to simulate a 4DCT acquisition as well as a recently published
      method for phase sorting. The modified XCAT phantom can be used to generate more
      realistic imaging data for enhanced testing of algorithms for CT reconstruction,
      tumor tracking, and dose reconstruction.

PMID- 22595982
TI  - Hypoxia augments oscillatory blood flow in brachial artery during leg cycling.
AB  - PURPOSE: The purpose of the present study was to elucidate changes in mean blood
      flow and oscillatory blood flow patterns to the inactive limb during leg cycle
      exercise in hypoxia. We hypothesized that oscillatory antegrade and retrograde
      blood flows to the nonworking limb would increase during incremental cycle
      exercise under hypoxic condition. METHODS: Eight males participated in this
      study. Two maximal exercise tests were conducted on a semirecumbent cycle
      ergometer while subjects inhaled a normoxic (inspired oxygen fraction [FIO2] =
      0.21) or hypoxic gas mixture (FIO2 = 0.12). The exercise began at an initial
      power output of 30 W, and workload was increased by 30 W every 2 min until
      exhaustion. Brachial artery blood velocity and diameter were simultaneously
      recorded during exercise using Doppler ultrasonography. Blood flow was calculated
      using the cross-sectional area of the brachial artery and time-averaged mean
      blood velocity. RESULTS: Mean blood flow decreased until 120 W in both trials (P
      < 0.05), and the magnitude of the reduction in mean blood flow was not different
      between two trials. However, the extent of changes in antegrade and retrograde
      blood flows during submaximal exercise in hypoxia was greater than that in
      normoxia (normoxia vs hypoxia: antegrade blood flow at 120 W = 145.4 +/- 10.3 vs
      172.4 +/- 9.0 mL.min and retrograde blood flow at 120 W = -89.1 +/- 4.9 vs -118.1
      +/- 6.2 mL.min, P < 0.05). CONCLUSIONS: These results indicate that hypoxia has a
      significant effect on oscillatory antegrade/retrograde blood flow patterns in
      nonworking limb during cycling exercise.

PMID- 22595983
TI  - Dyspnea, chest wall hyperinflation, and rib cage distortion in exercising
      patients with chronic obstructive pulmonary disease.
AB  - PURPOSE: Whether dyspnea, chest wall dynamic hyperinflation, and abnormalities of
      rib cage motion are interrelated phenomena has not been systematically evaluated
      in patients with chronic obstructive pulmonary disease (COPD). Our hypothesis
      that they are not interrelated was based on the following observations: (i)
      externally imposed expiratory flow limitation is associated with no rib cage
      distortion during strenuous incremental exercise, with indexes of hyperinflation
      not being correlated with dyspnea, and (ii) end-expiratory chest wall volume may
      either increase or decrease during exercise in patients with COPD, with those who
      hyperinflate being as breathless as those who do not. METHODS: Sixteen patients
      breathed either room air or 50% supplemental O2 at 75% of peak exercise in
      randomized order. We evaluated the volume of chest wall (V(cw)) and its
      compartments: the upper rib cage (V(rcp)), lower rib cage (V(rca)), and abdomen
      (V(ab)) using optoelectronic plethysmography; rib cage distortion was assessed by
      measuring the phase angle shift between V(rcp) and V(rca). RESULTS: Ten patients
      increased end-expiratory V(cw) (V(cw,ee)) on air. In seven hyperinflators and
      three non-hyperinflators, the lower rib cage paradoxed inward during inspiration
      with a phase angle of 63.4 degrees  +/- 30.7 degrees  compared with a normal
      phase angle of 16.1 degrees  +/- 2.3 degrees  recorded in patients without rib
      cage distortion. Dyspnea (by Borg scale) averaged 8.2 and 9 at the end of
      exercise on air in patients with and without rib cage distortion, respectively.
      At iso-time during exercise with oxygen, decreased dyspnea was associated with a
      decrease in ventilation regardless of whether patients distorted the rib cage,
      dynamically hyperinflated, or deflated the chest wall. CONCLUSIONS: Dyspnea,
      chest wall dynamic hyperinflation, and rib cage distortion are not interrelated
      phenomena.

PMID- 22595984
TI  - Physical activity and inflammation in a multiethnic cohort of women.
AB  - PURPOSE: Many cross-sectional studies using data from a single time point have
      reported that higher levels of physical activity or fitness are associated with
      lower levels of inflammatory markers, but data examining change are limited, as
      are race/ethnicity-specific data. The purpose of this study was to examine the
      associations between physical activity and inflammation assessed at two time
      points among women of different race/ethnicities. METHODS: A total of 1355
      postmenopausal women (301 whites, 300 blacks, 300 Hispanics, 300 Asians/Pacific
      Islanders, and 154 American Indians) age 50-79 yr were studied. Participants were
      from 40 US cities and were free of cardiovascular disease and cancer. At baseline
      and year 3, women reported their recreational physical activities and provided
      blood samples, which were analyzed for several inflammatory markers. RESULTS: In
      cross-sectional analyses, after adjusting for several potential confounders
      including body mass index, higher physical activity levels were generally related
      to lower inflammatory marker concentrations. For example, P values for a linear
      trend of lower C-reactive protein levels across physical activity tertiles at
      baseline were <0.0001 in all women and 0.94, 0.09, 0.002, 0.20, and 0.10,
      respectively, for the five race/ethnic groups listed above. For interleukin 6,
      the corresponding P values were <0.0001, 0.0007, 0.01, 0.03, 0.37, and 0.004,
      respectively, at baseline. Relationships at year 3 were similar to baseline.
      However, there was no relation between changes in physical activity and changes
      in inflammatory markers during the 3-yr period. CONCLUSIONS: Among middle-age and
      older women overall, there were strong, inverse, cross-sectional associations
      between physical activity level and inflammatory markers. However, changes in
      inflammatory markers were unrelated to changes in physical activity. These data
      suggest a noncausal association between physical activity and inflammatory
      markers.

PMID- 22595985
TI  - Presence and duration of reactivity to pedometers in adults.
AB  - PURPOSE: This study aimed to examine the presence and duration of reactivity to
      wearing a pedometer and recording daily step counts in free-living adults.
      METHODS: On the first visit to the laboratory, 90 participants (69% were females,
      age = 26.8 +/- 13.0 yr, body mass index = 23.4 +/- 4.0 kg.m(-2)), blinded to the
      study aim, were provided with a sealed pedometer (New Lifestyles NL-800) and
      informed that it was a "body posture monitor" (covert condition). Participants
      wore the pedometer throughout waking hours for 1 wk. On their return to the
      laboratory, stored step counts were recorded, and participants were informed that
      the device was a pedometer. Participants wore the pedometer unsealed (no
      restriction on viewing the step count display) for 2 wk, during which they
      recorded their daily step count in a diary (diary condition). Mean daily step
      counts recorded during the covert condition and during weeks 1 and 2 of the diary
      condition were compared using a repeated-measures ANOVA. RESULTS: There was a
      significant overall effect of study condition (P < 0.001), with post hoc analyses
      revealing that mean daily step counts reported during the first week of the diary
      condition (9898 +/- 3002 steps per day) were significantly higher than those
      reported during the covert condition (8331 +/- 3010 steps per day) and during the
      second week of the diary condition (8226 +/- 3170 steps per day, P < 0.001).
      CONCLUSIONS: Reactivity to wearing unsealed pedometers and step count recording
      seems to last for 1 wk. In the absence of any intervention material, step counts
      return to normal levels during the second week of monitoring and therefore
      represent a more accurate estimate of habitual activity. These findings have
      important implications to both researchers and practitioners interested in the
      use of pedometers for physical activity surveillance and promotion.

PMID- 22595986
TI  - Lower limb movement symmetry cannot be assumed when investigating the stop-jump
      landing.
AB  - PURPOSE: When investigating lower limb landing biomechanics, researchers often
      assume movement symmetry between a participant's right and left lower limbs for
      the simplicity of data collection and analysis, although landing tasks often
      involve dual-limb motion. However, whether lower limb symmetry can be assumed
      when investigating dynamic, sport-specific movements such as the stop-jump has
      not been investigated. Therefore, this study aimed to determine whether there
      were any significant differences in selected kinetic, kinematic, and muscle
      activation patterns characterizing lower limb biomechanics displayed by the
      dominant limb compared with the nondominant limb of participants during a stop
      jump task. METHODS: Sixteen male athletes with normal patellar tendons on
      diagnostic imaging performed five successful stop-jump trials. Patellar tendon
      forces (FPT), ground reaction forces, three-dimensional kinematics, and EMG
      activity of seven lower limb muscles were recorded for the dominant and
      nondominant lower limbs during each trial. RESULTS: During the horizontal landing
      phase, the dominant lower limb sustained a significantly higher FPT and peak net
      knee joint extension moment compared with the nondominant lower limb.
      Furthermore, during the vertical landing phase, the dominant lower limb sustained
      significantly lower vertical but higher posterior ground reaction forces compared
      with the nondominant lower limb. Other variables did not significantly vary as a
      function of lower limb dominance. CONCLUSIONS: It is recommended that researchers
      clearly identify their primary outcome variables and ensure that their
      experimental design, particularly in terms of lower limb dominance, provides an
      appropriate framework to investigate possible mechanics underlying unilateral and
      bilateral knee joint injuries during dual-limb movements such as the stop-jump
      task.

PMID- 22595987
TI  - Molecular signatures of the three stem cell lineages in hydra and the emergence
      of stem cell function at the base of multicellularity.
AB  - How distinct stem cell populations originate and whether there is a clear stem
      cell "genetic signature" remain poorly understood. Understanding the evolution of
      stem cells requires molecular profiling of stem cells in an animal at a basal
      phylogenetic position. In this study, using transgenic Hydra polyps, we reveal
      for each of the three stem cell populations a specific signature set of
      transcriptions factors and of genes playing key roles in cell type-specific
      function and interlineage communication. Our data show that principal functions
      of stem cell genes, such as maintenance of stemness and control of stem cell self
      renewal and differentiation, arose very early in metazoan evolution. They are
      corroborating the view that stem cell types shared common, multifunctional
      ancestors, which achieved complexity through a stepwise segregation of function
      in daughter cells.

PMID- 22595988
TI  - Irritable bowel syndrome: methods, mechanisms, and pathophysiology. Methods to
      assess visceral hypersensitivity in irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder,
      characterized by recurrent abdominal pain or discomfort in combination with
      disturbed bowel habits in the absence of identifiable organic cause. Visceral
      hypersensitivity has emerged as a key hypothesis in explaining the painful
      symptoms in IBS and has been proposed as a "biological hallmark" for the
      condition. Current techniques of assessing visceral perception include the
      computerized barostat using rectal distensions, registering responses induced by
      sensory stimuli including the flexor reflex and cerebral evoked potentials, as
      well as brain imaging modalities such as functional magnetic resonance imaging
      and positron emission tomography. These methods have provided further insight
      into alterations in pain processing in IBS, although the most optimal method and
      condition remain to be established. In an attempt to give an overview of these
      methods, a literature search in the electronic databases PubMed and MEDLINE was
      executed using the search terms "assessment of visceral pain/visceral
      nociception/visceral hypersensitivity" and "irritable bowel syndrome." Both
      original articles and review articles were considered for data extraction. This
      review aims to discuss currently used modalities in assessing visceral
      perception, along with advantages and limitations, and aims also to define future
      directions for methodological aspects in visceral pain research. Although novel
      paradigms such as brain imaging and neurophysiological recordings have been
      introduced in the study of visceral pain, confirmative studies are warranted to
      establish their robustness and clinical relevance. Therefore, subjective verbal
      reporting following rectal distension currently remains the best-validated
      technique in assessing visceral perception in IBS.

PMID- 22595989
TI  - Expression of TNFAIP3 in intestinal epithelial cells protects from DSS- but not
      TNBS-induced colitis.
AB  - Intestinal epithelial cells (IEC) maintain gastrointestinal homeostasis by
      providing a physical and functional barrier between the intestinal lumen and
      underlying mucosal immune system. The activation of NF-kappaB and prevention of
      apoptosis in IEC are required to maintain the intestinal barrier and prevent
      colitis. How NF-kappaB activation in IEC prevents colitis is not fully
      understood. TNFalpha-induced protein 3 (TNFAIP3) is a NF-kappaB-induced gene that
      acts in a negative-feedback loop to inhibit NF-kappaB activation and also to
      inhibit apoptosis; therefore, we investigated whether TNFAIP3 expression in the
      intestinal epithelium impacts susceptibility of mice to colitis. Transgenic mice
      expressing TNFAIP3 in IEC (villin-TNFAIP3 Tg mice) were exposed to dextran sodium
      sulfate (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS), and the severity and
      characteristics of mucosal inflammation and barrier function were compared with
      wild-type mice. Villin-TNFAIP3 Tg mice were protected from DSS-induced colitis
      and displayed reduced production of NF-kappaB-dependent inflammatory cytokines.
      Villin-TNFAIP3 Tg mice were also protected from DSS-induced increases in
      intestinal permeability and induction of IEC death. Villin-TNFAIP3 Tg mice were
      not protected from colitis induced by TNBS. These results indicate that TNFAIP3
      expression in IEC prevents colitis involving DSS-induced IEC death, but not
      colitis driven by T cell-mediated inflammation. As TNFAIP3 inhibits NF-kappaB
      activation and IEC death, expression of TNFAIP3 in IEC may provide an avenue to
      inhibit IEC NF-kappaB activation without inducing IEC death and inflammation.

PMID- 22595990
TI  - Hyperhomocysteinemia decreases intestinal motility leading to constipation.
AB  - Elevated levels of plasma homocysteine (Hcy) called hyperhomocysteinemia (HHcy)
      have been implicated in inflammation and remodeling in intestinal vasculature,
      and HHcy is also known to aggravate the pathogenesis of inflammatory bowel
      disease (IBD). Interestingly, colon is the pivotal site that regulates Hcy levels
      in the plasma. We hypothesize that HHcy decreases intestinal motility through
      matrix metalloproteinase-9 (MMP-9)-induced intestinal remodeling leading to
      constipation. To verify this hypothesis, we used C57BL/6J or wild-type (WT),
      cystathionine beta-synthase (CBS(+/-)), MMP-9(-/-), and MMP-9(-/-) + Hcy mice.
      Intestinal motility was assessed by barium meal studies and daily feces output.
      Plasma Hcy levels were measured by HPLC. Expression of ICAM-1, inducible nitric
      oxide synthase, MMP-9, and tissue inhibitors of MMPs was studied by Western blot
      and immunohistochemistry. Reactive oxygen species (ROS) including super oxide
      were measured by the Invitrogen molecular probe method. Tissue nitric oxide
      levels were assessed by a commercially available kit. Plasma Hcy levels in the
      treated MMP-9 group mice were comparable to CBS(+/-) mice. Barium meal studies
      suggest that intestinal motility is significantly decreased in CBS(+/-) mice
      compared with other groups. Fecal output-to-body weight ratio was significantly
      reduced in CBS(+/-) mice compared with other groups. There was significant
      upregulation of MMP-9, iNOS, and ICAM-1 expression in the colon from CBS(+/-)
      mice compared with WT mice. Levels of ROS, superoxide, and inducible nitric oxide
      were elevated in the CBS(+/-) mice compared with other groups. Results suggest
      that HHcy decreases intestinal motility due to MMP-9-induced intestinal
      remodeling leading to constipation.

PMID- 22595991
TI  - Simultaneous detection of gastric acid and histamine release to unravel the
      regulation of acid secretion from the guinea pig stomach.
AB  - Gastric acid secretion is regulated by three primary components that activate the
      parietal cell: histamine, gastrin, and acetylcholine (ACh). Although much is
      known about these regulatory components individually, little is known on the
      interplay of these multiple activators and the degree of regulation they pose on
      the gastric acid secretion mechanism. We utilized a novel dual-sensing approach,
      where an iridium oxide sensor was used to monitor pH and a boron-doped diamond
      electrode was used for the detection of histamine from in vitro guinea pig
      stomach mucosal sections. Under basal conditions, gastrin was shown to be the
      main regulatory component of the total acid secretion and directly activated the
      parietal cell rather than by mediating gastric acid secretion through the release
      of histamine from the enterochromaffin-like cell, although both pathways were
      active. Under stimulated conditions with ACh, the gastrin and histamine
      components of the total acid secretion were not altered compared with levels
      observed under basal conditions, suggestive that ACh had no direct effect on the
      enterochromaffin-like cell and G cell. These data identify a new unique approach
      to investigate the regulation pathways active during acid secretion and the
      degree that they are utilized to drive total gastric acid secretion. The findings
      of this study will enhance our understanding on how these signaling mechanisms
      vary under pathophysiology or therapeutic management.

PMID- 22595993
TI  - Serotonin availability in rat colon is reduced during a Western diet model of
      obesity.
AB  - Constipation and slowed transit are associated with diet-induced obesity,
      although the mechanisms by which this occurs are unclear. Enterochromaffin (EC)
      cells within the intestinal epithelium respond to mechanical stimulation with the
      release of serotonin [5-hydroxytryptamine (5-HT)], which promotes transit. Thus
      our aim was to characterize 5-HT availability in the rat colon of a
      physiologically relevant model of diet-induced obesity. EC cell numbers were
      determined immunohistochemically in chow-fed (CF) and Western diet-fed (WD) rats,
      while electrochemical methods were used to measure mechanically evoked (peak) and
      steady-state (SS) 5-HT levels. Fluoxetine was used to block the 5-HT reuptake
      transporter (SERT), and the levels of mRNA for tryptophan hydroxylase 1 and SERT
      were determined by quantitative PCR, and SERT protein was determined by Western
      blot. In WD rats, there was a significant decrease in the total number of EC
      cells per crypt (0.86 +/- 0.06 and 0.71 +/- 0.05 in CF and WD, respectively),
      which was supported by a reduction in the levels of 5-HT in WD rats (2.9 +/- 1.0
      and 10.5 +/- 2.6 MUM at SS and peak, respectively) compared with CF rats (7.3 +/-
      0.4 and 18.4 +/- 3.4 MUM at SS and peak, respectively). SERT-dependent uptake of
      5-HT was unchanged, which was supported by a lack of change in SERT protein
      levels. In WD rats, there was no change in tryptophan hydroxylase 1 mRNA but an
      increase in SERT mRNA. In conclusion, our data show that foods typical of a WD
      are associated with decreased 5-HT availability in rat colon. Decreased 5-HT
      availability is driven primarily by a reduction in the numbers and/or 5-HT
      content of EC cells, which are likely to be associated with decreased intestinal
      motility in vivo.

PMID- 22595992
TI  - Rapid protein kinase D1 signaling promotes migration of intestinal epithelial
      cells.
AB  - We have examined the role of protein kinase D1 (PKD1) signaling in intestinal
      epithelial cell migration. Wounding monolayer cultures of intestinal epithelial
      cell line IEC-18 or IEC-6 induced rapid PKD1 activation in the cells immediately
      adjacent to the wound edge, as judged by immunofluorescence microscopy with an
      antibody that detects the phosphorylated state of PKD1 at Ser(916), an
      autophosphorylation site. An increase in PKD1 phosphorylation at Ser(916) was
      evident as early as 45 s after wounding, reached a maximum after 3 min, and
      persisted for >=15 min. PKD1 autophosphorylation at Ser(916) was prevented by the
      PKD family inhibitors kb NB 142-70 and CRT0066101. A kb NB 142-70-sensitive
      increase in PKD autophosphorylation was also elicited by wounding IEC-6 cells.
      Using in vitro kinase assays after PKD1 immunoprecipitation, we corroborated that
      wounding IEC-18 cells induced rapid PKD1 catalytic activation. Further results
      indicate that PKD1 signaling is required to promote migration of intestinal
      epithelial cells into the denuded area of the wound. Specifically, treatment with
      kb NB 142-70 or small interfering RNAs targeting PKD1 markedly reduced wound
      induced migration in IEC-18 cells. To test whether PKD1 promotes migration of
      intestinal epithelial cells in vivo, we used transgenic mice that express
      elevated PKD1 protein in the small intestinal epithelium. Enterocyte migration
      was markedly increased in the PKD1 transgenic mice. These results demonstrate
      that PKD1 activation is one of the early events initiated by wounding a monolayer
      of intestinal epithelial cells and indicate that PKD1 signaling promotes the
      migration of these cells in vitro and in vivo.

PMID- 22595994
TI  - Catalyst development for organocatalytic hydrosilylation of aromatic ketones and
      ketimines.
AB  - A new family of Lewis basic 2-pyridyl oxazolines have been developed, which can
      act as efficient organocatalysts for the enantioselective reduction of prochiral
      aromatic ketones and ketimines with trichlorosilane, a readily available and
      inexpensive reagent. 1-Isoquinolyl oxazoline, derived from mandelic acid, was
      identified as the most efficient catalyst of the series, capable of delivering
      high enantioselectivities in the reduction of both ketones (up to 94% ee) and
      ketimines (up to 89% ee).

PMID- 22595996
TI  - Corannulenylferrocenes: towards a 1D, non-covalent metal-organic nanowire.
AB  - A class of novel corannulene-derived ferrocene donor-acceptor systems has been
      synthesized by straight-forward Negishi-type coupling of iodocorannulene. Their
      solid state structures have been studied crystallographically and found to
      exhibit unique inter- and intramolecular slipped stacking interactions.

PMID- 22595997
TI  - Efficient thiocyanate-free sensitizer: a viable alternative to N719 dye for dye
      sensitized solar cells.
AB  - We have designed and synthesized a new thiocyanate-free sensitizer coded as SPS
      01 and used it as the sensitizer in a TiO(2) based nanocrystalline dye-sensitized
      solar cell (DSSC). SPS-01 exhibits strong visible absorption properties with
      maximum peak around at 532 nm. The overall power conversion efficiency (PCE) of a
      DSSC sensitized with SPS-01 (7.96%) is higher than that of N719 (7.30%) under
      identical experimental conditions. This high PCE is attributed mainly due to the
      improvement in the short circuit current.

PMID- 22595998
TI  - "Phil" (1969) by Chuck Close (B. 1940).

PMID- 22596002
TI  - Neuroprosthetic learning utilizes the same neural circuitry required for motor
      learning.

PMID- 22596003
TI  - Promotion of neuronal recovery following experimental SCI via direct inhibition
      of glial scar formation.

PMID- 22596004
TI  - Failure:  the key to success.

PMID- 22596005
TI  - Higher field magnetic resonance imaging studies of mesial temporal pathology:  a
      pathology and imaging correlative study.

PMID- 22596006
TI  - Resetting the stem cell clock:  impact of the systemic milieu on oligodendrocyte
      precursor cell differentiation and remyelination.

PMID- 22596008
TI  - Seeing is believing--spinal chamber for spinal cord injury research.

PMID- 22596007
TI  - Therapeutic stem cells encapsulated in a synthetic extracellular matrix
      selectively kill tumor cells, delay tumor growth, and increase survival in a
      mouse resection model of malignant glioma.

PMID- 22596009
TI  - Genetic mutations and tissue type lead to heterogeneous metabolic profiles in
      tumors.

PMID- 22596010
TI  - CIC and FUBP1 mutations in oligodendroglioma.

PMID- 22596011
TI  - The ERSET trial of early surgery for mesial temporal lobe epilepsy: results and
      frustrations.

PMID- 22596013
TI  - An unusual form of superficially disseminated glioma in children: report of 3
      cases.
AB  - Three children, aged 4, 5, and 9 years, had an insidious onset of ataxia.
      Magnetic resonance imaging (MRI) showed hydrocephalus and countless foci of high
      T2 signal coating the cerebellum, basilar cisterns, brainstem, and fourth
      ventricle. Similar lesions were present in the spinal cord. Symptoms were
      relatively mild given the massive tumor burden. Biopsies were composed of
      superficially infiltrating cells with oligodendroglioma-like features
      (perinuclear halos and cytologic monotony) and microcysts. Classical cytogenetic
      analysis of 2 cases showed normal karyotypes. Chromosome fluorescence in situ
      hybridization revealed 1p36 deletion with intact 19q in 2 cases and no
      abnormality in one. A similar combination of clinical, MRI, and histopathologic
      findings has been reported previously in 10 other cases. The pathologic findings
      suggest a glioma with diffuse or multifocal superficial origin and do not
      correspond to a described entity in the current World Health Organization (WHO)
      classification of brain tumors.

PMID- 22596014
TI  - Combined omega3 and omega6 supplementation in children with attention-deficit
      hyperactivity disorder (ADHD) refractory to methylphenidate treatment: a double
      blind, placebo-controlled study.
AB  - Children (6-12 years) with attention-deficit hyperactivity disorder (ADHD) being
      treated with methylphenidate and standard behavior therapy for more than 6
      months, whose parents reported no improvement in behavior and academic learning,
      were randomly assigned to receive supplementation with a combined omega3 and
      omega6 preparation or a placebo. Outcome was measured at 3 and 6 months after
      treatment using a self-assessment checklist completed by the parents.
      Statistically significant improvement was found in the treatment group compared
      with the placebo group (P < .01) in the following measures: restlessness,
      aggressiveness, completing work, and academic performance. Statistically
      significant improvement was not found at 3 months of treatment between groups but
      was evident at 6 months of treatment (P < .05) with inattention, impulsiveness,
      and cooperation with parents and teachers. Distractibility failed to show
      improvement. Effect sizes ranged from 0.3 to 1.1 at 3 months and 0.2 to 1.4 at 6
      months for individual symptom variables.

PMID- 22596015
TI  - Epilepsy and narcolepsy-cataplexy in a child.
AB  - We report a 5-year-old boy with epilepsy and narcolepsy-cataplexy. He developed
      myoclonic seizures at the age of 4 years, which manifested as head shaking to the
      left. Approximately 6 months later, narcolepsy-cataplexy with excessive daytime
      sleepiness occurred. Although a short-time electroencephalography (EEG) and 24
      hour ambulatory EEG monitoring found epileptiform discharges, no seizures were
      determined. Oxcarbazepine was used and led to increased attacks. Video EEG
      testing finally confirmed the diagnosis of epilepsy; therefore, valproate was
      given and seizures were controlled completely. Typical cataplexy triggered by
      laughing, together with the positive multiple sleep latency tests confirmed a
      diagnosis of narcolepsy-cataplexy. Human leukocyte antigens DQB1*0602 was
      positive, and the hypocretin level in cerebrospinal fluid was found to be
      decreased. Combination of valproate, methylphenidate, and clomipramine treatment
      improved the symptoms of both narcolepsy-cataplexy and seizure. The coexistence
      of both disorders in this single patient indicated that there might be a common
      mechanism between epilepsy and narcolepsy-cataplexy.

PMID- 22596016
TI  - A novel STXBP1 mutation causes focal seizures with neonatal onset.
AB  - Mutations of the syntaxin binding protein 1 (STXBP1) have been associated with
      severe infantile epileptic encephalopathies (Ohtahara syndrome and West
      syndrome), but also with moderate to severe cognitive impairment and nonsyndromic
      epilepsy. We have studied a white infant who presented with focal seizures at age
      2 weeks. Brain imaging was unremarkable. The electroencephalograph (EEG)
      demonstrated normal background frequency content but with multifocal sharp waves
      and no evidence of the typical patterns associated with Ohtahara or West
      syndrome. Therapy with levetiracetam and oxcarbazepine effectively managed the
      seizure episodes. Investigation of genes associated with infantile forms of
      epilepsy such as SCN1A, SCN1B, and ARX were negative, but we identified a novel
      single-nucleotide duplication mutation, c.931dupT (p.S311FfsX3), in exon 11 of
      the STXBP1 gene. This previously unreported STXBP1 mutation in a subject with
      neonatal-onset focal seizures broadens the spectrum of clinically relevant human
      disorders caused by STXBP1 mutations.

PMID- 22596017
TI  - A proposal for the definition of Hirayama disease and monomelic amyotrophy.

PMID- 22596019
TI  - The Rabe amination after a century: direct addition of N-heterocycles to carbonyl
      compounds.
AB  - A catalytic version of the Rabe electrophilic amination is presented. This kind
      of reaction was originally employed in 1918 in a key step for the conversion of
      quinotoxine to quinine. Ketones and alpha-substituted aldehydes give the
      corresponding alpha-aminated carbonyl compounds in moderate yield. alpha,alpha
      Unsubstituted aldehydes give rise to amino ketones via a novel rearrangement.

PMID- 22596020
TI  - The Akaike information criterion in DCE-MRI: does it improve the haemodynamic
      parameter estimates?
AB  - The Akaike information criterion and the associated Akaike weights (AW) rank
      pharmacokinetic models on the basis of goodness-of-fit and number of parameters.
      The usefulness of this information for improving the haemodynamic parameter
      estimates from DCE-MRI was investigated through two examples. In each of these,
      the estimates from the two-compartment exchange model (2CXM) were combined on the
      basis of the AW with those of a simplified model (either the uptake model or the
      extended Tofts model). Data were simulated using the 2CXM for a range of
      experimental and tissue conditions. Two multimodel approaches exploiting the AW
      were investigated: the 'bestmodel' approach which selects the parameter estimates
      from the model with highest AW and the 'weighted model' approach in which AW
      weighted averages of the estimates from the competing models are calculated.
      Although these approaches were shown to be beneficial in some cases, they were
      found to frequently lead to unexpected increases in the bias and/or uncertainty
      of the resulting parameter estimates. Within the limited scope of this simulation
      study, the use of the Akaike criterion showed no systematic benefit over a
      fitting strategy involving only the more complex model.

PMID- 22596021
TI  - Persistent pain following lumbar disc replacement.
AB  - BACKGROUND: Pain patterns associated with the facet and sacroiliac joints
      following lumbar total disc replacement correlate with biomechanical modeling
      observations, such as load transfer to the posterior spinal elements in total
      disc replacement with an artificial disc. When conventional treatment options are
      exhausted, spinal cord stimulation (SCS) offers clinically favorable outcomes to
      treat intractable pain. OBJECTIVES: To contribute to the literature on
      neuroaugmentive techniques and on pain following disc replacement, and to
      highlight recent advances and forward-thinking concepts for nonsurgical
      intradiscal therapies. RESULTS: Three years of injection therapies and physical
      therapy did not significantly alleviate the patient's pain. A trial period of SCS
      rather than reoperation (fusion surgery) was elected. A constant-current multiple
      source SCS system was implanted. At 12-month follow-up for this system, the
      patient's pain had been reduced by more than 75%, and the patient reported
      improved quality of life, including a return of restful sleep. CONCLUSIONS: SCS
      is a viable technique to control pain associated with artificial disc implant.

PMID- 22596022
TI  - Influence of gender, age, and social norm on digital imaging use.
AB  - BACKGROUND: The adoption of digital imaging technology is a critical investment
      decision, and problems related to employee acceptance of the technology often are
      underestimated. Literature indicates that subjective normative factors, gender
      differences, and age may affect employee acceptance and use of new technology.
      Thus, understanding these influential factors is highly important to
      organizations. OBJECTIVE: To explore the relationships between gender, age,
      subjective normative factors, and the intention to use digital imaging technology
      in an environment where its use is mandatory. METHODS: A survey was used to
      investigate the applicability of a modified, theoretical technology acceptance
      model as a proposed model of radiographers' intention to use digital imaging
      technology. Structural equation modeling was used to test the theoretical model,
      and path analysis was used to examine dependence between variables. RESULTS:
      Although the data supports the modified versions of the theoretical technology
      acceptance model, the relationship between age and gender was very weak. When age
      and gender were removed from the model, voluntariness had a weak effect,
      suggesting other environmental factors play a larger role in explaining
      subjective normative factors within a radiologic environment. CONCLUSION: In
      contrast to other technology adoption studies, age and gender were not
      significantly associated with radiographers' acceptance and use of technology.
      Age and gender patterns do not apply to the adoption of digital imaging for this
      population. Therefore, one can conclude that in an environment in which digital
      imaging equipment use is mandated, additional sociocontextual variables play a
      role in the radiographers' intention to use the technology.

PMID- 22596024
TI  - Radiation safety for radiologic technologists.
AB  - Radiologic technologists and ancillary staff who work with or near ionizing
      radiation face possible short- and long-term effects of occupational radiation
      exposure. Further, radiologic technologists must minimize unnecessary exposure
      that risks the patient's safety, while achieving the best possible image or
      outcome. This article reviews occupational dose limits, dose calculation, devices
      used to measure exposure, and safety best practices that can help technologists
      keep radiation exposure "as low as reasonably achievable" for them and their
      patients. The article also discusses the appropriate use of mounted and mobile
      equipment, personal protective equipment, and safety features on imaging
      equipment to minimize unnecessary radiation exposure.

PMID- 22596025
TI  - Imaging rheumatic diseases.
AB  - Currently, more than 100 rheumatic diseases affect nearly 46 million Americans.
      Some of the most common rheumatic diseases include rheumatoid arthritis,
      osteoarthritis, lupus, psoriatic arthritis, ankylosing spondylitis, gout, and
      Sjogren syndrome. Rheumatic diseases are characterized by inflammation and lack
      of function in the joints and connective tissue. Early diagnosis and treatment of
      rheumatic disease is paramount in preventing damage and disability. Many
      radiologic modalities are used for diagnosing and monitoring these diseases, but
      for many, radiography remains the gold standard. Furthermore, imaging biomarkers
      may play an important role in diagnosis and treatment of rheumatic diseases in
      the future.

PMID- 22596027
TI  - Solving grid cutoff.

PMID- 22596028
TI  - Standardized patients in education.

PMID- 22596030
TI  - Parents in nuclear medicine suites.

PMID- 22596031
TI  - Close encounters of the patient kind.

PMID- 22596032
TI  - Patient page. Your first mammogram.

PMID- 22596033
TI  - Stroke and CT Perfusion.
AB  - Stroke is one of the leading causes of long-term disability and the fourth
      leading cause of death in the United States, killing more than 137,000 people a
      year. Time is critical during a stroke because prompt diagnosis and subsequent
      treatment can prevent the potential loss of brain function. Radiologic
      technologists who work in computed tomography (CT) must know how to perform CT
      perfusion and understand stroke diagnosis. This article provides information
      regarding strokes and CT perfusion techniques, including data acquisition,
      postprocessing, and interpretation.

PMID- 22596034
TI  - Mammography and litigation.
AB  - Mammography is perhaps the most heavily legislated medical procedure, and medical
      malpractice lawsuits are filed against mammographers for several reasons,
      including mammogram misread and delayed diagnosis. Perhaps the driving force
      behind mammography litigation is public perception of mammography's
      effectiveness. Surveys have indicated that the public attributes 100% sensitivity
      to mammography, whereas its actual sensitivity is approximately 79%. Fear of
      litigation affects mammography practice, and several initiatives have been
      suggested to address the problem of rampant mammography litigation, including
      increasing public awareness, to improve working conditions for mammographers and
      to ensure the future of this lifesaving procedure.

PMID- 22596035
TI  - Meta-B-entacenes: new polycyclic aromatics incorporating two fused borepin rings.
AB  - The synthesis of new boron-containing acenes (meta-B-entacenes) is reported.
      These compounds exhibit slightly non-planar core geometries with blue-shifted
      spectral properties and more negative electrochemical reduction potentials
      relative to known para isomers. Polarizable pi-extended architectures were
      realized via cross-coupling procedures with chloro-functionalized precursors.

PMID- 22596036
TI  - Implementing baby-friendly practices: strategies for success.
AB  - Breastfeeding is widely viewed as the optimal feeding method for infants among
      professional nursing and medical organizations. Its health benefits have been
      comprehensively studied and documented for both infants and mothers. Hospitals
      and birthing centers can strongly influence the outcomes for mothers who choose
      to breastfeed by establishing effective breastfeeding behaviors immediately after
      birth and during the hospital stay. The Baby-Friendly USA initiative outlines 10
      steps to successful breastfeeding. Although these steps have been successfully
      supported in practice, they can be difficult to implement due to a variety of
      factors, including resistance to change. Specific steps generate more barriers to
      overcome than others--namely exclusive breastfeeding without supplementation or
      pacifiers, rooming-in for 23 out of 24 hours, and skin-to-skin contact with a
      parent immediately after birth and during the hospital stay. Our hospital spent 5
      years implementing Baby-Friendly practices to prepare for a successful site
      visit. In the process, barriers to key Baby-Friendly steps were overcome through
      creative approaches and strategic education for staff, physicians, and parents.
      The purpose of this article is to outline specific actions taken that assisted
      our hospital in its successful journey. Those actions and strategies will
      hopefully be of value to others in their journey toward designation.

PMID- 22596037
TI  - Identification of mothers at risk for postpartum depression by hospital-based
      perinatal nurses.
AB  - In the western world, most women deliver their infants in a hospital setting. The
      purposes of this article are to provide guidelines and suggest best practices
      related to hospital-based care for postpartum depression by perinatal nurses;
      with this information, policies, procedures, and educational programs can be
      implemented to improve nursing care of new mothers. Hospital-based perinatal
      nurses need to "launch" new mothers from the hospital into the community so that
      the new mothers are prepared for self-monitoring for symptoms of depression, and
      know what steps to take if they do experience depressive symptoms.

PMID- 22596038
TI  - Impact of magnitude and percentage of global sagittal plane correction on health
      related quality of life at 2-years follow-up.
AB  - BACKGROUND: Sagittal plane malalignment has been established as the main
      radiographic driver of disability in adult spinal deformity (ASD). OBJECTIVE: To
      evaluate the amount of sagittal correction needed for a patient to perceive
      improvement (minimal clinically important difference, MCID) in health-related
      quality of life (HRQOL) scores. METHODS: This was a multicenter, retrospective
      analysis of prospectively consecutively enrolled ASD patients. Inclusion
      criterion was a sagittal vertical axis (SVA) >80 mm. Demographic, radiographic,
      and HRQOL preoperative and 2-year postsurgery data were collected. Surgical
      treatment was categorized based on SVA correction: <60 mm, 60 mm to 120 mm, and
      >120 mm. Changes in parameters were analyzed using paired t test, 1-way analysis
      of variance, and chi2 test. RESULTS: Seventy-six patients (preoperative SVA = 140
      mm) were analyzed; each subgroup revealed significant HRQOL improvements
      following surgery. Compared with the <60 mm correction group, the likelihood of
      reaching MCID was significantly improved for the >120 mm group (Oswestry
      Disability Index) but not for the 60 mm to 120 mm group. A significantly greater
      likelihood of reaching MCID thresholds was observed for corrections above 66% of
      preoperative SVA. CONCLUSION: Best HRQOL outcomes for ASD patients with severe
      sagittal plane deformity were obtained with a correction >120 mm for SVA and at
      least 66% of correction. Although lesser amounts of SVA correction yielded
      clinical improvement, the rate of MCID threshold improvement was not
      significantly different for mild or modest corrections. These results underline
      the need for complete sagittal plane deformity correction if high rates of HRQOL
      benefit are sought for patients with marked sagittal plane deformity.

PMID- 22596039
TI  - Journal club: Intraoperative confocal microscopy for brain tumors: a feasibility
      analysis in humans.

PMID- 22596040
TI  - Angiographic detection and characterization of "cryptic venous anomalies"
      associated with spinal cord cavernous malformations using flat-panel catheter
      angiotomography.
AB  - BACKGROUND: Spinal cord cavernous malformations (CMs) are associated with 2 types
      of angiographically occult "cryptic venous anomalies," which differ in location
      with respect to the spinal cord. The anatomic distinction between superficial and
      intramedullary is important in that the latter heighten the risks of CM
      resection. OBJECTIVE: To report the observations of both types of cryptic venous
      anomalies documented during spinal digital subtraction angiography enhanced with
      flat-panel catheter angiotomography (FPCA). METHODS: Spinal digital subtraction
      angiography enhanced with FPCA was performed in 2 adult patients with magnetic
      resonance imaging--documented intramedullary spinal cord CMs and prominent,
      nonspecific flow voids at the same levels. FPCA was obtained by selective
      injection of left T4 (case 1) and left T9 (case 2) with 5F Cobra 2 catheters
      (Terumo, Japan) during a 20-second rotational acquisition. Thirty milliliters of
      a 75% saline and 25% contrast solution (Omnipaque 300; GE) was administered. The
      rotational data set was reconstructed on a dedicated workstation (Leonardo;
      Siemens, Erlangen, Germany) through the use of regular and high-resolution
      matrixes, 0.4- and 0.1-mm voxel size, respectively. RESULTS: Spinal digital
      subtraction angiography was unremarkable in both cases. In case 1, FPCA findings
      indicated an atypical network of prominent posterior perimedullary veins. In case
      2, FPCA identified radially oriented channels forming a caput medusae pattern
      collecting into an enlarged intramedullary vein. CONCLUSION: The unique ability
      of FPCA to image the spinal venous system enables the angiographic detection and
      characterization of abnormal spinal veins associated with CMs. Differentiating
      between the types of associated cryptic venous malformations may aid in surgical
      planning because the intramedullary type is associated with a higher risk of
      surgical complication.

PMID- 22596041
TI  - Ferrocenyl catechols: synthesis, oxidation chemistry and anti-proliferative
      effects on MDA-MB-231 breast cancer cells.
AB  - The synthesis and anti-tumoral properties of a series of compounds possessing a
      ferrocenyl group tethered to a catechol via a conjugated system is presented. On
      MDA-MB-231 breast cancer cell lines, the catechol compounds display a similar or
      greater anti-proliferative potency (IC(50) values ranging from 0.48-1.21 MUM)
      than their corresponding phenolic analogues (0.57-12.7 MUM), with the highest
      activity found for species incorporating the [3]ferrocenophane motif. On the
      electrochemical timescale, phenolic compounds appear to oxidize to the quinone
      methide, while catechol moieties form the o-quinone by a similar mechanism.
      Chemical oxidation of selected compounds with Ag(2)O confirms this interpretation
      and demonstrates the probable involvement of such oxidative metabolites in the in
      vitro activity of these species.

PMID- 22596043
TI  - Investigation of the effects of alcohol on sleep using actigraphy.
AB  - AIMS: To investigate the effect of alcohol consumption on the sleep and mood of
      healthy individuals in a college-based, mixed gender population. METHODS: Forty
      seven individuals participated in this study, of whom 33 consumed alcohol and
      were included in the analysis. Sleep quality was objectively recorded using
      actigraphy. Subjects completed a daily sleep diary and bipolar Profile of Mood
      States Questionnaire, recording the subjective perception of sleep quality and
      waking mood respectively. RESULTS: Mean self-reported alcohol consumption among
      the drinkers was 84.6 ml ethanol/night. Mean total sleep time for those who
      consumed less than the mean reported intake was significantly reduced on alcohol.
      This reduction in sleep time was associated with increased wakefulness in the
      second half of the night, a truncated sleeping period and increased waking
      fatigue. This rebound wakefulness could not be demonstrated in those who consumed
      higher than the mean intake, though these individuals also reported increased
      waking fatigue. CONCLUSION: These results add weight to the clinical evidence
      that ethanol should not be used as a hypnotic due to its potential to affect both
      the quantity and quality of sleep. The finding that total sleep time is reduced
      on low doses of alcohol is novel and may arise from measuring sleep in an
      environment other than the sleep laboratory.

PMID- 22596044
TI  - Osteocyte apoptosis and lipid infiltration as mechanisms of alcohol-induced bone
      loss.
AB  - AIMS: We carried out an in vivo study to assess the relationship between increase
      in adiposity in the marrow and osteocyte apoptosis in the case of alcohol-induced
      bone loss. METHODS AND RESULTS: After alcohol treatment, the number of apoptotic
      osteocytes was increased and lipid droplets were accumulated within the
      osteocytes, the bone marrow and the cortical bone micro-vessels. At last, we
      found an inverse correlation between bone mineral density and osteocyte apoptosis
      and strong significant correlations between the osteocyte apoptotic number and
      lipid droplet accumulation in osteocyte and bone micro-vessels. CONCLUSION: These
      data show that alcohol-induced bone loss is associated with osteocyte apoptosis
      and lipid accumulation in the bone tissue. This lipid intoxication, or 'bone
      steatosis', is correlated with lipid accumulation in bone marrow and blood micro
      vessels.

PMID- 22596042
TI  - Oxidative effects of chronic ethanol consumption on the functions of heart and
      kidney: folic acid supplementation.
AB  - AIMS: The principal aim of this study was to investigate the oxidative effects of
      chronic ethanol consumption on the functions of the heart and the kidney and the
      possible modification of this effect by folic acid supplementation. Moreover, in
      order to find whether this oxidative profile affects cardiovascular function,
      parameters such as heart rate and glomerular filtration rate were also assessed.
      METHODS: Four experimental groups of rats were used: control, ethanol-exposed,
      control supplemented with folic acid and ethanol-exposed plus folic acid. Ethanol
      exposed rats were subjected to a chronic ethanol treatment (2 months), in which
      the level of alcohol reaches 30% v/v. Diet and ethanol solution were provided ad
      libitum, and folic acid supplementation was 8 vs. 2 ppm. Energy intake,
      creatinine clearance and heart rate were determined. Antioxidant enzyme activity
      and lipid and protein peroxidation of the kidney and the heart were measured by
      the spectrophotometric method. RESULTS: Ethanol increases heart size and catalase
      (CAT) activity and decreases lipid peroxidation in heart without changing heart
      rate. However, in the kidney, ethanol decreases CAT activity, increases lipid
      peroxidation and decreases glomerular filtration rate. Folic acid supplementation
      avoids these situations; it does not, however, improve glomerular function.
      CONCLUSION: Chronic ethanol consumption has many effects on the antioxidant
      enzymatic activity of the heart and the kidney, leading to increased renal lipid
      peroxidation prevented by folic acid supplementation.

PMID- 22596045
TI  - Design of a ratiometric fluorescent probe for benzenethiols based on a thiol
      sulfoxide reaction.
AB  - A novel thiol-sulfoxide reaction based ratiometric probe for benzenethiols was
      synthesized and evaluated. The probe features a chemospecific reduction over a pH
      range of 1-10 by benzenethiols with a marked emission color change, enabling the
      highly selective detection and is promising for applications.

PMID- 22596046
TI  - Experimental study of the water-to-air stopping power ratio of monoenergetic
      carbon ion beams for particle therapy.
AB  - Reference dosimetry with ionization chambers requires a number of chamber
      specific and beam-specific calibration factors. For carbon ion beams, IAEA report
      TRS-398 yields a total uncertainty of 3% in the determination of the absorbed
      dose to water, for which the biggest contribution arises from the water-to-air
      stopping power ratio (s(w, air)), with an uncertainty of 2%. The variation of
      (s(w, air)) along the treatment field has been studied in several Monte Carlo
      works presented over the last few years. Their results were, in all cases,
      strongly dependent on the choice of mean ionization potentials (I-values) for air
      and water. A smaller dependence of (s(w, air)) with penetration depth was
      observed. Since a consensus on I(w, air) and I(air) has not yet been reached, the
      validity of such studies for clinical use cannot be assessed independently. Our
      approach is based on a direct experimental measurement of water-equivalent
      thicknesses of different air gaps at different beam energies. A theoretical
      expression describing the variation of the stopping power ratio with kinetic
      energy, s(w,air)(E), was derived from the Bethe-Bloch formula and fit to the
      measured data, yielding a coherent pair of I(w) and I(air) values with
      I(air)/I(w) = 1.157 +/- 0.023. Additionally, the data from five different beam
      energies were combined in an average value of s(w,air) = 1.132 +/- 0.003
      (statistical) +/- 0.003 (variation over energy range), valid for monoenergetic
      carbon ion beams at the plateau area of the depth dose distribution. A detailed
      uncertainty analysis was performed on the data, in order to assess the
      limitations of the method, yielding an overall standard uncertainty below 1% in
      s(w,air)(E). Therefore, when properly combined with the appropriate models for
      the fragment spectra, our experimental work can contribute to narrow the
      uncertainty margins currently in use in absorbed dose to water determination for
      dosimetry of carbon ion beam radiotherapy.

PMID- 22596047
TI  - Electronic structure, molecular electrostatic potential and spectral
      characteristics of pillar[6]arene hosts and their complexes with n
      octyltriethylammonium ions.
AB  - Electronic structure, charge distribution and (1)H NMR in pillar[6]arene (P6)
      conformers, their diisobutoxy derivatives and their host-guest complexes have
      been investigated by employing the density functional theory. It has been shown
      that a P6 conformer obtained by flipping of alternate hydroquinone units turns
      out to be of lowest energy, owing to the hydrogen bonded network at both rims of
      the host. As opposed to this, a conformer void of hydrogen bonding interactions
      has largely been destabilized. The O-HO interactions are analyzed using molecular
      electrostatic potential topography as a tool. Modification of a P6 host by
      substituting a diisobutoxy group at reactive phenols (DIBP6) renders rigid pillar
      shape architecture to the host in which electron-rich regions are localized
      within the cavity and near portals. Complexation of n-octyltriethylammonium ions
      (n-OTEA) with P6 and DIBP6 reveals qualitatively different binding patterns. It
      has been shown that the conformer in which n-OTEA penetrates from the lower rim
      of the host and partially encapsulates within the P6 cavity turns out to be 1.4
      kJ mol(-1) lower in energy than the complex showing complete guest encapsulation.
      Host-guest binding patterns, viz. encapsulation or portal interactions, can be
      distinguished from (1)H NMR chemical shifts. The shielding of ethyl and n-octyl
      chain protons in an n-OTEA?DIBP6 complex points to encapsulation of the guest
      which has been rationalized from natural bond orbital analyses. These inferences
      are in consonance with (1)H NMR experiments. 

PMID- 22596048
TI  - Ephrin-B2-activated peripheral blood mononuclear cells from diabetic patients
      restore diabetes-induced impairment of postischemic neovascularization.
AB  - We hypothesized that in vitro treatment of peripheral blood mononuclear cells (PB
      MNCs) from diabetic patients with ephrin-B2/Fc (EFNB2) improves their
      proangiogenic therapeutic potential in diabetic ischemic experimental models.
      Diabetes was induced in nude athymic mice by streptozotocin injections. At 9
      weeks after hyperglycemia, 10(5) PB-MNCs from diabetic patients, pretreated by
      EFNB2, were intravenously injected in diabetic mice with hindlimb ischemia. Two
      weeks later, the postischemic neovascularization was evaluated. The mechanisms
      involved were investigated by flow cytometry analysis and in vitro cell
      biological assays. Paw skin blood flow, angiographic score, and capillary density
      were significantly increased in ischemic leg of diabetic mice receiving EFNB2
      activated diabetic PB-MNCs versus those receiving nontreated diabetic PB-MNCs.
      EFNB2 bound to PB-MNCs and increased the adhesion and transmigration of PB-MNCs.
      Finally, EFNB2-activated PB-MNCs raised the number of circulating vascular
      progenitor cells in diabetic nude mice and increased the ability of endogenous
      bone marrow MNCs to differentiate into cells with endothelial phenotype and
      enhanced their proangiogenic potential. Therefore, EFNB2 treatment of PB-MNCs
      abrogates the diabetes-induced stem/progenitor cell dysfunction and opens a new
      avenue for the clinical development of an innovative and accessible strategy in
      diabetic patients with critical ischemic diseases.

PMID- 22596049
TI  - Identification of adipose tissue dendritic cells correlated with obesity
      associated insulin-resistance and inducing Th17 responses in mice and patients.
AB  - T-cell regulation in adipose tissue provides a link between inflammation and
      insulin resistance. Because of alterations in adipose tissue T-cell composition
      in obesity, we aimed to identify the antigen-presenting cells in adipose tissue
      of obese mice and patients with insulin resistance. Dendritic cells (DCs) and T
      cells were studied in mice and in two cohorts of obese patients. In lean mice,
      only CD11c(+) DCs were detected in adipose tissue. Adoptive transfer of naive
      CD4(+) T cells in Rag1(-/-) mice led to a predominant Th1 response in adipose
      tissue. In contrast, during obesity DCs (human CD11c(+)CD1c(+) and mouse
      CD11c(high)F4/80(low)) accumulated in adipose tissue. CD11c(high)F4/80(low) DCs
      from obese mice induced Th17 differentiation. In patients, the presence of
      CD11c(+)CD1c(+) DCs correlated with the BMI and with an elevation in Th17 cells.
      In addition, these DCs led to ex vivo Th17 differentiation. CD1c gene expression
      further correlated with homeostatic model assessment-insulin resistance in the
      subcutaneous adipose tissue of obese patients. We show for the first time the
      presence and accumulation of specific DCs in adipose tissue in mouse and human
      obesity. These DCs were functional and could be important regulators of adipose
      tissue inflammation by regulating the switch toward Th17 cell responses in
      obesity-associated insulin resistance.

PMID- 22596050
TI  - Intrinsic differences in adipocyte precursor cells from different white fat
      depots.
AB  - Obesity and body fat distribution are important risk factors for the development
      of type 2 diabetes and metabolic syndrome. Evidence has accumulated that this
      risk is related to intrinsic differences in behavior of adipocytes in different
      fat depots. In the current study, we demonstrate that adipocyte precursor cells
      (APCs) isolated from visceral and subcutaneous white adipose depots of mice have
      distinct patterns of gene expression, differentiation potential, and response to
      environmental and genetic influences. APCs derived from subcutaneous fat
      differentiate well in the presence of classical induction cocktail, whereas those
      from visceral fat differentiate poorly but can be induced to differentiate by
      addition of bone morphogenetic protein (BMP)-2 or BMP-4. This difference
      correlates with major differences in gene expression signature between
      subcutaneous and visceral APCs. The number of APCs is higher in obesity-prone
      C57BL/6 mice than obesity-resistant 129 mice, and the number in both depots is
      increased by up to 270% by exposure of mice to high-fat diet. Thus, APCs from
      visceral and subcutaneous depots are dynamic populations, which have intrinsic
      differences in gene expression, differentiation properties, and responses to
      environmental/genetic factors. Regulation of these populations may provide a new
      target for the treatment and prevention of obesity and its metabolic
      complications.

PMID- 22596051
TI  - Insulin sensitivity and beta-cell function in adults born preterm and their
      children.
AB  - We aimed to evaluate insulin secretion and insulin sensitivity in adults born
      preterm and their children. Subjects were adults born both preterm and at term,
      with their children aged 5-10 years born at term. Insulin sensitivity and
      secretion were assessed using hyperglycemic clamps in adults and frequently
      sampled intravenous glucose tolerance tests using Bergman minimal model in
      children. In total, 52 adults aged 34-38 years participated (31 born preterm,
      mean gestational age 33.3 weeks). Adults born preterm were less insulin sensitive
      than those born at term (19.0 +/- 2.5 vs. 36.3 +/- 5.2 mg . kg(-1) . min(-1)mU .
      L; P < 0.05) with compensatory increased first-phase insulin secretion (56.1 +/-
      8.5 vs. 25.3 +/- 3.7 mU/L; P < 0.001) but similar disposition index indicating
      appropriate insulin secretion. These differences were independent of sex and
      remained when subjects born <32 weeks' gestation were excluded from analyses. In
      total, 61 children were studied (37 of preterm parents, mean age 7.9 +/- 0.3
      years). Children of parents born preterm had similar insulin sensitivity to
      children of parents born at term, but a correlation between parental and
      offspring insulin sensitivity was noted only among children of parents born
      preterm. In conclusion, adults born preterm have insulin resistance in
      midadulthood, but this was not associated with insulin resistance in their
      children.

PMID- 22596052
TI  - Cytokine and chemokine production by human pancreatic islets upon enterovirus
      infection.
AB  - Enteroviruses of the human enterovirus B species (HEV-Bs) (e.g., coxsackie B
      viruses [CVBs] and echoviruses) have been implicated as environmental factors
      that trigger/accelerate type 1 diabetes, but the underlying mechanism remains
      elusive. The aim of this study was to gain insight into the cytokines and
      chemokines that are produced by human pancreatic islets upon infection with CVBs.
      To this end, we studied the response of human islets of Langerhans upon mock or
      CVB3 infection. Using quantitative PCR, we showed that upon CVB3 infection,
      transcription of interferon (IFN), IFN-stimulated genes, and inflammatory genes
      was induced. Analysis of secreted cytokines and chemokines by Luminex technology
      confirmed production and secretion of proinflammatory cytokines (e.g.,
      interleukin [IL]-6 and tumor necrosis factor-alpha) as well as various
      chemotactic proteins, such as IFN-gamma-induced protein 10, macrophage
      inflammatory protein (MIP)-1alpha, MIP-1beta, and IL-8. Infection with other HEV
      Bs induced similar responses, yet their extent depended on replication
      efficiency. Ultra violet-inactivated CVB3 did not induce any response, suggesting
      that virus replication is a prerequisite for antiviral responses. Our data
      represent the first comprehensive overview of inflammatory mediators that are
      secreted by human islets of Langerhans upon CVB infection and may shed light on
      the role of enteroviruses in type 1 diabetes pathogenesis.

PMID- 22596053
TI  - Early-outgrowth bone marrow cells attenuate renal injury and dysfunction via an
      antioxidant effect in a mouse model of type 2 diabetes.
AB  - Cell therapy has been extensively investigated in heart disease but less so in
      the kidney. We considered whether cell therapy also might be useful in diabetic
      kidney disease. Cognizant of the likely need for autologous cell therapy in
      humans, we sought to assess the efficacy of donor cells derived from both healthy
      and diabetic animals. Eight-week-old db/db mice were randomized to receive a
      single intravenous injection of PBS or 0.5 * 10(6) early-outgrowth cells (EOCs)
      from db/m or db/db mice. Effects were assessed 4 weeks after cell infusion.
      Untreated db/db mice developed mesangial matrix expansion and tubular epithelial
      cell apoptosis in association with increased reactive oxygen species (ROS) and
      overexpression of thioredoxin interacting protein (TxnIP). Without affecting
      blood glucose or blood pressure, EOCs not only attenuated mesangial and
      peritubular matrix expansion, as well as tubular apoptosis, but also diminished
      ROS and TxnIP overexpression in the kidney of db/db mice. EOCs derived from both
      diabetic db/db and nondiabetic db/m mice were equally effective in ameliorating
      kidney injury and oxidative stress. The similarly beneficial effects of cells
      from healthy and diabetic donors highlight the potential of autologous cell
      therapy in the related clinical setting.

PMID- 22596057
TI  - Nontraditional life-history choices: what can "intermediates" tell us about
      evolutionary transitions between modes of invertebrate development?
AB  - Mode of development in marine invertebrates has been largely viewed as a
      dichotomy between small eggs that develop into free-living planktotrophic larvae
      and large eggs that bypass the larval stage and develop directly into juveniles.
      Modes of development that could be categorized as "intermediate" between these
      two extremes include facultative feeding larvae, short-lived planktotrophic
      larvae, dispersal dimorphisms, and poecilogony (in which nutritional mode varies
      within a species). These intermediates are rare. The few species-level
      phylogenies available that include them do not generally support the
      interpretation of intermediates as necessary, ephemeral transitional forms.
      Instead, they support the idea that intermediates are well adapted to their
      environments but that either these environments are short-lived relative to the
      frequency of speciation, or speciation events are associated with shifts in the
      mode of development. Each of the different intermediate forms could have evolved
      in response to variable environments. The phenotypically plastic intermediates
      could be a response to predictable environmental variation. Facultative feeding
      larvae and short-lived planktotrophic larvae could reflect conservative bet
      hedging in response to unpredictable environmental variation, whereas poecilogony
      with mixed clutches could represent the alternative: diversifying bet-hedging.
      Since environmental variability is common, it remains an enigma why these
      intermediates are so rare. Discovery of more intermediates, and their careful
      description in terms of the level of variation expressed within, and among,
      clutches, and among females and populations, as well as determination of the
      genetic and environmental influences on this variation, will provide valuable
      test-cases for theories of the evolution of alternative phenotypes.

PMID- 22596054
TI  - Myostatin inhibition prevents diabetes and hyperphagia in a mouse model of
      lipodystrophy.
AB  - Lipodystrophies are characterized by a loss of white adipose tissue, which causes
      ectopic lipid deposition, peripheral insulin resistance, reduced adipokine
      levels, and increased food intake (hyperphagia). The growth factor myostatin
      (MSTN) negatively regulates skeletal muscle growth, and mice with MSTN inhibition
      have reduced adiposity and improved insulin sensitivity. MSTN inhibition may
      therefore be efficacious in ameliorating diabetes. To test this hypothesis, we
      inhibited MSTN signaling in a diabetic model of generalized lipodystrophy to
      analyze its effects on glucose metabolism separate from effects on adipose mass.
      A-ZIP/F1 lipodystrophic mice were crossed to mice expressing a dominant-negative
      MSTN receptor (activin receptor type IIB) in muscle. MSTN inhibition in A-ZIP/F1
      mice reduced blood glucose, serum insulin, triglyceride levels, and the rate of
      triglyceride synthesis, and improved insulin sensitivity. Unexpectedly,
      hyperphagia was normalized by MSTN inhibition in muscle. Blood glucose and
      hyperphagia were reduced in double mutants independent of the adipokine leptin.
      These results show that the effect of MSTN inhibition on insulin sensitivity is
      not secondary to an effect on adipose mass and that MSTN inhibition may be an
      effective treatment for diabetes. These results further suggest that muscle may
      play a heretofore unappreciated role in regulating food intake.

PMID- 22596058
TI  - Antipredator behavior promotes diversification of feeding strategies.
AB  - Animals often facultatively engage in less risky behavior when predators are
      present. Few studies, however, have investigated whether, or how, such predator
      mediated behavior promotes diversification. Here, we ask whether tadpoles of the
      spadefoot toad Scaphiopus couchii have a diminished ability to utilize a
      potentially valuable resource--anostracan fairy shrimp--because of behavioral
      responses to predation risk imposed by carnivorous tadpoles of the genus Spea.
      Observations of a congener of Sc. couchii that occurs in allopatry with Spea,
      coupled with an ancestral character state reconstruction, revealed that Sc.
      couchii's ancestors likely consumed shrimp. By experimentally manipulating the
      presence of Spea carnivore-morph tadpoles in microcosms, we found that Sc.
      couchii reduce feeding and avoid areas where both Spea carnivores and shrimp
      occur. We hypothesize that the recurrent expression of such behaviors in
      sympatric populations of Sc. couchii led to the evolutionary fixation of a
      detritivorous feeding strategy, which is associated with a reduced risk of
      predation from Spea carnivores. Generally, predator-mediated behavior might play
      a key role in promoting diversification of feeding strategies.

PMID- 22596056
TI  - Exploring androgen-regulated pathways in teleost fish using transcriptomics and
      proteomics.
AB  - In the environment, there are aquatic pollutants that disrupt androgen signaling
      in fish. Laboratory and field-based experiments have utilized omics technologies
      to characterize the molecular mechanisms underlying androgen-receptor
      agonism/antagonism. Transcriptomics and proteomics studies with 17beta
      trenbolone, a growth-promoting pharmaceutical found in water systems surrounding
      cattle feed lots, and androgens such as 17alpha-methyltestosterone and 17alpha
      methyldihydrotestosterone, have been conducted in ovary and liver of fish that
      include the fathead minnow (FHM) (Pimephales promelas), common carp (Cyprinus
      carpio), Qurt medaka (Oryzias latipes), and zebrafish (Danio rerio). In this mini
      review, we survey recent omics studies in fish and reveal that, despite the
      diversity of species and tissues examined, there are common cellular responses
      that are observed with waterborne androgenic treatments. Recurring themes in gene
      ontology include apoptosis, transport and oxidation of lipids, synthesis and
      transport of hormones, immune response, protein metabolism, and cell
      proliferation. However, we also discuss other mechanisms other than androgen
      receptor (AR) activation, such as responses to toxicant stress, estrogen receptor
      agonism, aromatization of androgens into estrogens, and inhibitory feedback
      mechanisms by high levels of androgens that may also explain molecular responses
      in fish. To further explore androgen-responsive protein networks, a sub-network
      enrichment analysis was performed on protein data collected from the livers of
      female FHMs exposed to 17beta-trenbolone. We construct a putative AR-regulated
      protein/cell process network in the liver that includes B-lymphocyte
      differentiation, xenobiotic clearance, low-density lipoprotein oxidation,
      proliferation of smooth muscle cells, and permeability of blood vessels. We
      demonstrate that construction of protein networks can offer insight into cell
      processes that are potentially regulated by androgens.

PMID- 22596059
TI  - Overcoming barriers to Baby-Friendly status: one hospital's experience.
AB  - The journey toward Baby-Friendly status at Jersey Shore University Medical Center
      in Neptune, NJ began with a desire to improve overall breastfeeding rates at the
      hospital. Although evidence showed that hospitals that incorporated some or all
      of the Ten Steps to Successful Breastfeeding had improved breastfeeding rates, it
      was difficult to overcome barriers that prevented the hospital physicians and
      nursing staff from seeing the value in adopting this quality initiative. Long
      standing practices combined with misinformation compounded the problem. That
      situation changed when several factors nationally and statewide came together to
      create a prime environment for implementation of the Baby-Friendly Hospital
      Initiative. This article will discuss the barriers that one hospital encountered
      and the strategies used to overcome these common barriers to achieving Baby
      Friendly status. This hospital is not yet designated as Baby-Friendly but is
      awaiting the outcome of a site visit in 2012.

PMID- 22596060
TI  - Extremely large breast abscess in a breastfeeding mother.
AB  - Puerperal mastitis often occurs in younger primiparous women. Most cases occur
      between 3 and 8 weeks postpartum. If mastitis results in the formation of a
      breast abscess, surgical drainage or needle aspiration is most commonly
      performed. We report a case of an extremely large breast abscess in a primiparous
      20-year-old woman, which presented 6 weeks postpartum. Surgical incision and
      evacuation of 2 liters of exudate were performed, and intravenous antibiotics
      therapy was administered. On the sixth day after incision, we secondarily closed
      the wound. Examination after 3 months showed symmetrical breasts with a small
      scar in the incision area of the right breast. A high degree of suspicion and
      adequate diagnostic procedures are essential to avoid delay in the treatment of
      mastitis and breast abscess and thereby prevent unnecessary surgical treatment.

PMID- 22596061
TI  - Disinfection by-product formation potentials in wastewater effluents and their
      reductions in a wastewater treatment plant.
AB  - Disinfection by-product formation potentials (DBPFPs) in wastewater effluents
      from eight wastewater treatment plants (WWTPs) were investigated. In addition, a
      WWTP with one primary effluent and two different biological treatment processes
      was selected for a comparative study. Formation potential tests were carried out
      to determine the levels of DBP precursors in wastewater. WWTPs that achieved
      better organic matter removal and nitrification tended to result in lower DBPFPs
      in effluents. For the WWTP with two processes, haloacetic acid, trihalomethane,
      and chloral hydrate precursors were predominant DBP precursors in the primary and
      secondary effluents. The percent reductions of haloacetonitrile and haloketone
      formation potentials averaged at 96% which was high in comparison to the
      reductions of other classes of DBPFPs. In addition, biological treatment changed
      the DBPFP speciation profile by lowering the HAAFP/THMFP ratio. The eight plant
      survey and the comparative analysis of the WWTP with two processes implied that
      besides nitrification, there may be other confounding factors impacting DBPFPs.
      Oxic and anoxic conditions, formation and degradation of soluble microbial
      products had impacts on the DBPFP reductions. This information can be used by
      water and wastewater professionals to better control wastewater-derived DBPs in
      downstream potable water supplies.

PMID- 22596062
TI  - Absence of seasonal changes in FSHR gene expression in the cat cumulus-oocyte
      complex in vivo and in vitro.
AB  - Domestic cat oocytes are seasonally sensitive to FSH. Compared with those
      collected during the breeding season, oocytes from the nonbreeding (NB) season
      require more FSH during in vitro maturation to achieve comparable developmental
      competence. This study tested the hypothesis that this seasonal variation was due
      to altered expression of FSH receptors (FSHR) and/or FSH-induced genes. Relative
      expression levels of FSHR mRNA and FSH-enhanced gene estrogen receptor beta
      (ESR2) were measured by qPCR in whole ovaries and immature cumulus-oocyte
      complexes (COCs) isolated from cat ovaries during the natural breeding vs NB
      seasons. Expression levels of FSH-induced genes prostaglandin-endoperoxide
      synthase 2 (PTGS2), early growth response protein-1 (EGR1), and epidermal growth
      factor receptor (EGFR) were examined in mature COCs from both seasons that were
      a) recovered in vivo or b) matured in vitro with conventional (1 MUg/ml) or high
      (10 MUg/ml) FSH concentrations. Overall, FSHR mRNA levels were lower in whole
      ovaries during the NB compared with breeding season but were similar in immature
      COCs, whereas ESR2 levels did not differ in either group between intervals. We
      observed changes in PTGS2, EGR1, and EGFR mRNA expression patterns across
      maturation in COCs within but not between the two seasons. The lack of seasonal
      differentiation in FSH-related genes was not consistent with the decreased
      developmental capacity of oocytes fertilized during the NB season. These findings
      reveal that the seasonal decrease in cat oocyte sensitivity to FSH occurs both in
      vivo and in vitro. Furthermore, this decline is unrelated to changes in
      expression of FSHR mRNA or mRNA of FSH-induced genes in COCs from antral
      follicles.

PMID- 22596063
TI  - The association between CDC42 and caveolin-1 is involved in the regulation of
      capacitation and acrosome reaction of guinea pig and mouse sperm.
AB  - In the mammalian sperm, the acrosome reaction (AR) is considered to be a
      regulated secretion that is an essential requirement for physiological
      fertilization. The AR is the all-or-nothing secretion system that allows for
      multiple membrane fusion events. It is a Ca(2)(+)-regulated exocytosis reaction
      that has also been shown to be regulated by several signaling pathways. CDC42 has
      a central role in the regulated exocytosis through the activation of SNARE
      proteins and actin polymerization. Furthermore, the lipid raft protein caveolin-1
      (CAV1) functions as a scaffold and guanine nucleotide dissociation inhibitor
      protein for CDC42, which is inactivated when associated with CAV1. CDC42 and
      other RHO proteins have been shown to localize in the acrosome region of
      mammalian sperm; however, their relationship with the AR is unknown. Here, we
      present the first evidence that CDC42 and CAV1 could be involved in the
      regulation of capacitation and the AR. Our findings show that CDC42 is activated
      early during capacitation, reaching an activation maximum after 20 min of
      capacitation. Spontaneous and progesterone-induced ARs were inhibited when sperm
      were capacitated in presence of secramine A, a specific CDC42 inhibitor. CAV1 and
      CDC42 were co-immunoprecipitated from the membranes of noncapacitated sperm; this
      association was reduced in capacitated sperm, and our data suggest that the
      phosphorylation (Tyr14) of CAV1 by c-Src is involved in such reductions. We
      suggest that CDC42 activation is favored by the disruption of the CAV1-CDC42
      interaction, allowing for its participation in the regulation of capacitation and
      the AR.

PMID- 22596064
TI  - Change in regional (somatic) near-infrared spectroscopy is not a useful indicator
      of clinically detectable low cardiac output in children after surgery for
      congenital heart defects.
AB  - OBJECTIVE: Near-infrared spectroscopy correlation with low cardiac output has not
      been validated. Our objective was to determine role of splanchnic and/or renal
      oxygenation monitoring using near-infrared spectroscopy for detection of low
      cardiac output in children after surgery for congenital heart defects. DESIGN:
      Prospective observational study. SETTING: Pediatric intensive care unit of a
      tertiary care teaching hospital. PATIENTS: Children admitted to the pediatric
      intensive care unit after surgery for congenital heart defects. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: We hypothesized that splanchnic and/or renal
      hypoxemia detected by near-infrared spectroscopy is a marker of low cardiac
      output after pediatric cardiac surgery. Patients admitted after cardiac surgery
      to the pediatric intensive care unit over a 10-month period underwent serial
      splanchnic and renal near-infrared spectroscopy measurements until extubation.
      Baseline near-infrared spectroscopy values were recorded in the first
      postoperative hour. A near-infrared spectroscopy event was a priori defined as
      >=20% drop in splanchnic and/or renal oxygen saturation from baseline during any
      hour of the study. Low cardiac output was defined as metabolic acidosis (pH
      <7.25, lactate >2 mmol/L, or base excess <=-5), oliguria (urine output <1
      mL/kg/hr), or escalation of inotropic support. Receiver operating characteristic
      analysis was performed using near-infrared spectroscopy event as a diagnostic
      test for low cardiac output. Twenty children were enrolled: median age was 5
      months; median Risk Adjustment for Congenital Heart Surgery category was 3 (1-6);
      median bypass and cross-clamp times were 120 mins (45-300 mins) and 88 mins (17
      157 mins), respectively. Thirty-one episodes of low cardiac output and 273 near
      infrared spectroscopy events were observed in 17 patients. The sensitivity and
      specificity of a near-infrared spectroscopy event as an indicator of low cardiac
      output were 48% (30%-66%) and 67% (64%-70%), respectively. On receiver operating
      characteristic analysis, neither splanchnic nor renal near-infrared spectroscopy
      event had a significant area under the curve for prediction of low cardiac output
      (area under the curve: splanchnic 0.45 [95% confidence interval 0.30-0.60], renal
      0.51 [95% confidence interval 0.37-0.65]). CONCLUSIONS: Splanchnic and/or renal
      hypoxemia as detected by near-infrared spectroscopy may not be an accurate
      indicator of low cardiac output after surgery for congenital heart defects.

PMID- 22596065
TI  - Socioeconomic impact on device-associated infections in pediatric intensive care
      units of 16 limited-resource countries: international Nosocomial Infection
      Control Consortium findings.
AB  - OBJECTIVES: We report the results of the International Nosocomial Infection
      Control Consortium prospective surveillance study from January 2004 to December
      2009 in 33 pediatric intensive care units of 16 countries and the impact of being
      in a private vs. public hospital and the income country level on device
      associated health care-associated infection rates. Additionally, we aim to
      compare these findings with the results of the Centers for Disease Control and
      Prevention National Healthcare Safety Network annual report to show the
      differences between developed and developing countries regarding device
      associated health care-associated infection rates. PATIENTS: A prospective
      cohort, active device-associated health care-associated infection surveillance
      study was conducted on 23,700 patients in International Nosocomial Infection
      Control Consortium pediatric intensive care units. METHODS: The protocol and
      methodology implemented were developed by International Nosocomial Infection
      Control Consortium. Data collection was performed in the participating intensive
      care units. Data uploading and analyses were conducted at International
      Nosocomial Infection Control Consortium headquarters on proprietary software.
      Device-associated health care-associated infection rates were recorded by
      applying Centers for Disease Control and Prevention National Healthcare Safety
      Network device-associated infection definitions, and the impact of being in a
      private vs. public hospital and the income country level on device-associated
      infection risk was evaluated. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Central line-associated bloodstream infection rates were similar in private,
      public, or academic hospitals (7.3 vs. 8.4 central line-associated bloodstream
      infection per 1,000 catheter-days [p < .35 vs. 8.2; p < .42]). Central line
      associated bloodstream infection rates in lower middle-income countries were
      higher than low-income countries or upper middle-income countries (12.2 vs. 5.5
      central line-associated bloodstream infections per 1,000 catheter-days [p < .02
      vs. 7.0; p < .001]). Catheter-associated urinary tract infection rates were
      similar in academic, public and private hospitals: (4.2 vs. 5.2 catheter
      associated urinary tract infection per 1,000 catheter-days [p = .41 vs. 3.0; p =
      .195]). Catheter-associated urinary tract infection rates were higher in lower
      middle-income countries than low-income countries or upper middle-income
      countries (5.9 vs. 0.6 catheter-associated urinary tract infection per 1,000
      catheter-days [p < .004 vs. 3.7; p < .01]). Ventilator-associated pneumonia rates
      in academic hospitals were higher than private or public hospitals: (8.3 vs. 3.5
      ventilator-associated pneumonias per 1,000 ventilator-days [p < .001 vs. 4.7; p <
      .001]). Lower middle-income countries had higher ventilator-associated pneumonia
      rates than low-income countries or upper middle-income countries: (9.0 vs. 0.5
      per 1,000 ventilator-days [p < .001 vs. 5.4; p < .001]). Hand hygiene compliance
      rates were higher in public than academic or private hospitals (65.2% vs. 54.8%
      [p < .001 vs. 13.3%; p < .01]). CONCLUSIONS: Country socioeconomic level
      influence device-associated infection rates in developing countries and need to
      be considered when comparing device-associated infections from one country to
      another.

PMID- 22596066
TI  - Predictive power of serum cystatin C to detect acute kidney injury and pediatric
      modified RIFLE class in children undergoing cardiac surgery.
AB  - OBJECTIVE: Acute kidney injury is a frequent and serious complication of
      cardiopulmonary bypass. In current clinical practice, serum creatinine is used to
      detect acute kidney injury. Cystatin C is a novel biomarker for kidney function
      that has been shown to be superior to serum creatinine in predicting acute kidney
      injury in adults after cardiopulmonary bypass. The aim of this study was to
      determine whether early cystatin C levels predict acute kidney injury associated
      with cardiopulmonary bypass in pediatric patients undergoing cardiac surgery and
      if cystatin C could predict pediatric-modified RIFLE (Risk, Injury, Failure,
      Loss, End-stage kidney disease) class and renal injury as determined by estimated
      glomerular filtration rate. We also investigated whether ultrafiltration during
      cardiopulmonary bypass affects cystatin C levels. DESIGN: Prospective,
      observational cohort study. SETTING: Cardiac intensive care unit in a tertiary,
      academic pediatric hospital. PATIENTS: One hundred pediatric patients who
      underwent cardiac surgery involving cardiopulmonary bypass. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Acute kidney injury was defined as a 50% increase
      in serum creatinine from a preoperative baseline anytime through postoperative
      day 4. Severity of acute kidney injury was determined by pediatric RIFLE class
      using estimated glomerular filtration rate criteria only. Renal injury was also
      determined by an absolute estimated glomerular filtration rate <80 mL/min/1.73 m.
      Cystatin C levels were measured before and after ultrafiltration. Twenty-eight
      patients (28%) developed acute kidney injury. Cystatin C predicted acute kidney
      injury as early as 8 hrs after surgery. When applying pediatric RIFLE criteria to
      the entire study, 30 patients reached "risk" and five developed "injury."
      Cystatin C was a good predictor of the development of "injury" (under the
      receiver operating characteristic curve, 0.834-0.875) and of renal injury by
      estimated glomerular filtration rate (under the receiver operating characteristic
      curve, 0.717-0.835) (all p < .05). Cystatin C levels decreased perioperatively
      and correlated with volume of fluid removed by ultrafiltration. CONCLUSIONS:
      Cystatin C is an early predictor of acute kidney injury in children after
      cardiopulmonary bypass. Cystatin C is a good predictor of pediatric RIFLE
      classification and of decreased estimated glomerular filtration rate after
      cardiopulmonary bypass. Serum cystatin C may be cleared by ultrafiltration.

PMID- 22596067
TI  - Hemolytic and thrombocytopathic characteristics of extracorporeal membrane
      oxygenation systems at simulated flow rate for neonates.
AB  - OBJECTIVE: A state-of-the-art centrifugal pump combined with hollow-fiber
      oxygenator for extracorporeal membrane oxygenation has potential advantages such
      as smaller priming volumes and decreased potential to cause tubing rupture as
      compared with the traditional roller head/silicone membrane systems. Adoption of
      these state-of-the-art systems has been slow in neonates as a result of past
      evidence of severe hemolysis that may lead to renal failure and increased
      mortality. Extracorporeal systems have also been linked to platelet dysfunction,
      a contributing factor toward intracranial hemorrhage, a leading cause of infant
      morbidity. Little data exist comparing the centrifugal systems with the roller
      systems in terms of hemolysis and platelet aggregation at low flow rates commonly
      used in neonatal extracorporeal membrane oxygenation. DESIGN: Prospective,
      comparative laboratory study. SETTING: University research laboratory. SUBJECTS:
      Centrifugal pump, roller pump, hollow-fiber oxygenator, and silicone membrane
      oxygenator. INTERVENTIONS: Comparative study using two pumps, the centrifugal
      Jostra Rotaflow (Maquet, Wayne, NJ) and the roller-head (Jostra, Maquet, Wayne,
      NJ), and two oxygenators, polymethlypentene Quadrox-D (Maquet) and silicone
      membrane (Medtronic, Minneapolis, MN). Five test runs of four circuit
      combinations were examined for hemolysis and platelet aggregation during 6 hrs of
      continuous use in a simulated in vitro extracorporeal membrane oxygenation
      circuit circulating whole swine blood at 300 mL/min. MEASUREMENTS AND MAIN
      RESULTS: Hemolysis was assessed by spectrophometric measurement of plasma-free
      hemoglobin. Platelet aggregation was evaluated using monoclonal CD61 antibody
      fluorescent flow cytometry profiles. All of the extracorporeal membrane
      oxygenation systems created plasma-free hemoglobin at a similar rate compared
      with static blood control. There was no difference in the mean normalized index
      of hemolysis of the centrifugal/hollow-fiber oxygenator system as compared with
      the roller-head/silicone membrane systems (0.0032 g/100 L vs. 0.0058 g/100 L, p
      >= .7). None of the extracorporeal membrane oxygenation systems had a significant
      increase in platelet aggregation above baseline. CONCLUSIONS: In a low-flow
      neonatal environment, a state-of-the-art centrifugal pump combined with new fiber
      type oxygenators appear to be safe in regard to hemolysis and platelet
      aggregation.

PMID- 22596068
TI  - Exposure to di(2-ethylhexyl) phthalate in premature neonates in a neonatal
      intensive care unit in Taiwan.
AB  - OBJECTIVE: Neonates are exposed to high levels of di(2ethylhexyl) phthalate
      through numerous medical procedures in the neonatal intensive care unit. Our aim
      was to assess the contribution of specific medical devices to the di(2
      ethylhexyl) phthalate exposure of neonates. DESIGN: Prospective. SETTING:
      University hospital. PATIENTS: We recruited 32 premature neonates, 20 with very
      low birth weight (<1500 g) and 12 with low birth weight (<2500 g), and 31
      controls at a neonatal intensive care unit from a medical center in central
      Taiwan. INTERVENTIONS: Interventions were based on a clinical need and used
      standard materials and devices, including endotracheal tubes, continuous positive
      airway pressure, oxygen hood, intravenous injection, intralipid injection, blood
      transfusion, orogastric tubes, nasogastric tubes, umbilical venous
      catheterization, umbilical arterial catheterization, chest tube, and isolate.
      MEASUREMENTS AND MAIN RESULTS: We recorded the medical procedures of each
      subject, collected their urine samples, and determined the urinary concentration
      of three metabolites of di(2-ethylhexyl) phthalate using reversed-phase high
      performance liquid chromatography-atmospheric pressure chemical ionization-tandem
      mass spectrometry. Median levels of di(2-ethylhexyl) phthalate metabolites in
      premature neonates treated with an endotracheal tube and orogastric tube or
      nasogastric tube were significantly higher than those not treated with an
      endotracheal tube, orogastric tube, or nasogastric tube. Median levels of di(2
      ethylhexyl) phthalate metabolites in premature neonates treated with intravenous
      injection were >= 2-fold higher than those of healthy controls who received
      intravenous injections (p = .01). Median levels of three di(2-ethylhexyl)
      phthalate metabolites were similar in very-low-birth-weight and low-birth-weight
      neonates. CONCLUSIONS: These data suggest that polyvinyl chloride-containing
      devices are the major defining factor in di(2-ethylhexyl) phthalate exposure
      levels in neonates in the neonatal intensive care unit. We urge the use of
      polyvinyl chloride-free or alternative materials in medical devices, especially
      for endotracheal tubes, orogastric tubes, nasogastric tubes, and intravenous
      tubing in the neonatal intensive care unit. The health effects of high di(2
      ethylhexyl) phthalate exposure on premature neonates in the neonatal intensive
      care unit is worthy of further investigation.

PMID- 22596069
TI  - Prolonged extracorporeal membrane oxygenation for children with respiratory
      failure.
AB  - OBJECTIVE: Extracorporeal membrane oxygenation is used to support children with
      respiratory failure. When extracorporeal membrane oxygenation duration is
      prolonged, decisions regarding ongoing support are difficult as a result of
      limited prognostic data. DESIGN: Retrospective case series. SETTING: Multi
      institutional data reported to the Extracorporeal Life Support Organization
      Registry. PATIENTS: Patients aged 1 month to 18 yrs supported with extracorporeal
      membrane oxygenation for respiratory failure from 1993 to 2007 who received
      support for >= 21 days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of
      the 3213 children supported with extracorporeal membrane oxygenation during the
      study period, 389 (12%) were supported >= 21 days. Median patient age was 9.1
      months (interquartile range, 2.5-41.7 months). Median weight was 6.7 kg
      (interquartile range, 3.5-15.8 kg). Survival for this group was 38%,
      significantly lower than survival reported for children supported <= 14 days
      (61%, p < .001). Among children supported with extracorporeal membrane
      oxygenation for >= 21 days, no differences were found between survivors and
      nonsurvivors with regard to acute pulmonary diagnosis, pre-extracorporeal
      membrane oxygenation comorbidities, pre-extracorporeal membrane oxygenation
      adjunctive therapies, or pre-extracorporeal membrane oxygenation blood gas
      parameters. Only peak inspiratory pressure was significantly different in
      survivors. Complications occurring on extracorporeal membrane oxygenation were
      more common among nonsurvivors. The use of inotropic infusion (odds ratio 1.64;
      95% confidence interval 1.07-2.52), acidosis (pH <7.2) during extracorporeal
      membrane oxygenation (odds ratio 2.62; 95% confidence interval 1.51-4.55), and
      male gender (odds ratio 1.95; 95% confidence interval 1.21-3.15) were
      independently associated with increased odds of death. CONCLUSION: Survival
      declines with duration of extracorporeal membrane oxygenation. Male gender and
      inadequate cardiorespiratory status during extracorporeal membrane oxygenation
      increased the risk of death. Prolonged support with extracorporeal membrane
      oxygenation appears reasonable unless multiorgan failure develops.

PMID- 22596070
TI  - Evolution of the Pediatric Advanced Life Support course: enhanced learning with a
      new debriefing tool and Web-based module for Pediatric Advanced Life Support
      instructors.
AB  - OBJECTIVE: To describe the history of the Pediatric Advanced Life Support course
      and outline the new developments in instructor training that will impact the way
      debriefing is conducted during Pediatric Advanced Life Support courses. OUTLINE:
      The Pediatric Advanced Life Support course, first released by the American Heart
      Association in 1988, has seen substantial growth and change over the past few
      decades. Over that time, Pediatric Advanced Life Support has become the standard
      for resuscitation training for pediatric healthcare providers in North America.
      The incorporation of high-fidelity simulation-based learning into the most recent
      version of Pediatric Advanced Life Support has helped to enhance the realism of
      scenarios and cases, but has also placed more emphasis on the importance of post
      scenario debriefing. We developed two new resources: an online debriefing module
      designed to introduce a new model of debriefing and a debriefing tool for real
      time use during Pediatric Advanced Life Support courses, to enhance and
      standardize the quality of debriefing by Pediatric Advanced Life Support
      instructors. In this article, we review the history of Pediatric Advanced Life
      Support and Pediatric Advanced Life Support instructor training and discuss the
      development and implementation of the new debriefing module and debriefing tool
      for Pediatric Advanced Life Support instructors. CONCLUSION: The incorporation of
      the debriefing module and debriefing tool into the 2011 Pediatric Advanced Life
      Support instructor materials will help both new and existing Pediatric Advanced
      Life Support instructors develop and enhance their debriefing skills with the
      intention of improving the acquisition of knowledge and skills for Pediatric
      Advanced Life Support students.

PMID- 22596072
TI  - Accuracy of tidal volume, compliance, and resistance measurements on neonatal
      ventilator displays: an in vitro assessment.
AB  - OBJECTIVE: To determine the accuracy of measures of respiratory mechanics derived
      from neonatal ventilators using an in vitro passive physical lung model to
      simulate newborn pulmonary conditions. DESIGN: Test lung models. SETTING:
      Laboratory-based measurements. INTERVENTIONS: Three test lungs were constructed
      to simulate three severities of neonatal lung disease, with ranges of compliance
      from 0.5 to 2.0 mL/cm H2O and resistance from 25 to 150 cm H2O/(L/sec). Each
      ventilator was tested using 27 combinations of peak inspiratory pressure (15-25
      cm H2O), positive end-expiratory pressure (5-7 cm H2O), and rate settings (20-60
      B/min). Data were compared for five different ventilators across simulated lung
      severity as the ratio of ventilator readout to test lung reference value. A ratio
      of 1.0 indicated a completely unbiased result. MAIN RESULTS: Overall, four of the
      five ventilators under-read expired tidal volume by about 1%-12% across all lung
      conditions, whereas the VIP Bird readout ranged from -4% to +4% bias. Changes in
      ventilator settings had only a modest effect on mechanics readout. As peak
      inspiratory pressure progressed from 15 to 25 cm H2O, bias in tidal volume
      readout changed from +5.0% to -2.5% (p < .001) in the VIP Bird, and from -11% to 
      9% (p < .001) in the Draeger Babylog VN500. Between positive end-expiratory
      pressure levels of 5 and 7 cm H2O, tidal volume bias in the Babylog varied
      between -13% and -7% (p < .001). In progressing from simulated normal to severely
      ill lung condition, bias in compliance measurements by the Avea and SLE5000
      increased from -18% to -40% whereas in the VIP Bird it remained between -17% to 
      13%, and in the Draeger Evita XL-neo it changed from +17% to -13% and from -8% to
      -16% in the Babylog. Ratio of ventilator resistance readout to reference value
      with progressing simulated lung condition changed from 2.0 to 1.0 for the Draeger
      Evita, 1.6 to 1.1 for the Babylog, 4.2 to 2.0 for the SLE, and from 11.7 to 5.6
      for the VIP Bird. The Avea, by design, did not display resistances >100 cm
      H2O/(L/sec), but overestimated the simulated normal lung resistance of 25 cm
      H2O/(L/sec) by a factor of 2.5. CONCLUSIONS: Neonatal ventilator respiratory
      mechanics measurements and computation methods need further standardization to be
      useful in clinical settings.

PMID- 22596071
TI  - An investigation into the prevalence and outcome of patients admitted to a
      pediatric intensive care unit with viral respiratory tract infections in Cape
      Town, South Africa.
AB  - OBJECTIVES: To describe the prevalence and outcome of patients admitted to a
      pediatric intensive care unit with viral respiratory tract infections. DESIGN:
      Retrospective descriptive study. SETTING: Pediatric intensive care unit in a
      tertiary pediatric hospital situated in Cape Town, South Africa. PATIENTS: All
      children (n = 195; 20% pediatric intensive care unit admissions) with positive
      respiratory viral isolates between April 1 and December 31, 2009. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: Demographic, clinical, laboratory, and
      outcome data were recorded from medical folders. Complete data were available for
      175 patients (median age [interquartile range] 4.7 months [2.3-12.9 months]; 49%
      male). One hundred four (59.4%) patients had comorbid conditions; 30 (17%) were
      HIV-infected. Rhinovirus (n = 76 [39%]), respiratory syncytial virus (n = 54
      [27.7%]), adenovirus (n = 30 [15.4%]), influenza A (n = 26 [13.3%]),
      parainfluenza (n = 23 [11.8%]), and human metapneumovirus (n = 12 [6.2%]) were
      most commonly isolated. Ninety-five infections (51.4%) were isolated >48 hrs
      after admission. Seasonal patterns were identified for respiratory syncytial
      virus, human metapneumovirus, and influenza A, whereas others occurred throughout
      the year. Twenty-five patients (14.3%) had more than one viral isolate. Presumed
      bacterial coinfection, which occurred in 68 (39%) patients (18 [26.5%] HIV
      infected), was associated with significantly longer pediatric intensive care unit
      and hospital stays but not with mortality. Twenty patients died (11%,
      standardized mortality ratio 0.64). High Pediatric Index of Mortality scores, HIV
      exposure and infection, nosocomial infection, and influenza A infection were
      associated with mortality. CONCLUSIONS: Viral respiratory tract infection is
      common in this pediatric intensive care unit associated with significant
      morbidity and mortality, which may relate to the high burden of comorbidity and
      HIV.

PMID- 22596073
TI  - Effects of wheelchair sports on respiratory muscle strength and thoracic mobility
      of individuals with spinal cord injury.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of wheelchair sports
      on respiratory muscle strength and the thoracic mobility of individuals with
      spinal cord injury. DESIGN: Thirty male subjects with chronic spinal cord injury
      (American Spinal Injury Association Impairment Scale grade A) took part in the
      study and were divided into four groups: sedentary subjects with quadriplegia (S
      QUAD, n = 7), wheelchair rugby athletes with quadriplegia (A-QUAD, n = 8),
      sedentary subjects with paraplegia (S-PARA, n = 6), and wheelchair basketball
      athletes with paraplegia (A-PARA, n = 9). The main outcome measures were maximal
      inspiratory and expiratory pressure and the respiratory coefficients at the
      axillary and xiphoid levels. RESULTS: A-QUAD group presented values significantly
      higher for all respiratory variables studied compared with the S-QUAD group. No
      significant differences in any of the respiratory variables were observed between
      S-PARA and A-PARA groups. There was a negative correlation between spinal cord
      injury level and respiratory variables for the S-QUAD and S-PARA groups. There
      were positive correlations in the A-QUAD group between time of training and
      maximal inspiratory pressure (adjusted R = 0.84; P = 0.001) and respiratory
      coefficients at the axillary level (adjusted R = 0.80; P = 0.002). CONCLUSIONS:
      Physical training seems to have a positive influence on respiratory muscle
      strength and thoracic mobility, especially in subjects with quadriplegia.

PMID- 22596074
TI  - The accuracy of new wheelchair users' predictions about their future wheelchair
      use.
AB  - OBJECTIVE: This study examined the accuracy of new wheelchair user predictions
      about their future wheelchair use. DESIGN: This was a prospective cohort study of
      84 community-dwelling veterans provided a new manual wheelchair. RESULTS: The
      association between predicted and actual wheelchair use was strong at 3 mos (phi
      coefficient = 0.56), with 90% of those who anticipated using the wheelchair at 3
      mos still using it (i.e., positive predictive value = 0.96) and 60% of those who
      anticipated not using it indeed no longer using the wheelchair (i.e., negative
      predictive value = 0.60, overall accuracy = 0.92). Predictive accuracy diminished
      over time, with overall accuracy declining from 0.92 at 3 mos to 0.66 at 6 mos.
      At all time points, and for all types of use, patients better predicted use as
      opposed to disuse, with correspondingly higher positive than negative predictive
      values. Accuracy of prediction of use in specific indoor and outdoor locations
      varied according to location. CONCLUSIONS: This study demonstrates the importance
      of better understanding the potential mismatch between the anticipated and actual
      patterns of wheelchair use. The findings suggest that users can be relied upon to
      accurately predict their basic wheelchair-related needs in the short-term.
      Further exploration is needed to identify characteristics that will aid users and
      their providers in more accurately predicting mobility needs for the long-term.

PMID- 22596076
TI  - Photoreaction channels of the guanine-cytosine base pair explored by long-range
      corrected TDDFT calculations.
AB  - Photoinduced processes in the Watson-Crick guanine-cytosine base pair are
      comprehensively studied by means of long-range corrected (LC) TDDFT calculations
      of potential energy profiles using the LC-BLYP and CAM-B3LYP functionals. The ab
      initio CC2 method and the conventional TDDFT method with the B3LYP functional are
      also employed to assess the reliability of the LC-TDDFT method. The present
      approach allows us to compare the potential energy profiles at the same
      computational level for excited-state reactions of the base pair, including
      single and double proton transfer between the bases and nonradiative decay via
      ring puckering in each base. In particular, long-range correction to the TDDFT
      method is critical for a qualitatively correct description of the proton transfer
      reactions. The calculated energy profiles exhibit low barriers for out-of-plane
      deformation of the guanine moiety in the locally-excited state, which is expected
      to lead to a conical intersection with the ground state, as well as for single
      proton transfer from guanine to cytosine with the well-known electron-driven
      proton transfer mechanism. Thus the present results suggest that both processes
      can compete in hydrogen-bonded base pairs and play a significant role in the
      mechanism of photostability.

PMID- 22596075
TI  - Attitudes of healthcare students and professionals toward patients with physical
      disability: a systematic review.
AB  - OBJECTIVE: Negative healthcare provider attitudes toward patients with physical
      disabilities may challenge the delivery of quality care to patients. The
      objective of this study was to systematically review published studies examining
      the attitudes of healthcare students and professionals toward patients with
      physical disabilities. DESIGN: In October 2011, we searched four electronic
      databases using the OVID platform. In addition, we screened citation lists.
      Independent reviewers completed the selection of articles and data abstraction by
      triplicate review using standardized and pilot tested forms. They resolved
      disagreements by discussion or with the help of an additional reviewer when
      necessary. Articles were included if they examined healthcare professionals' and
      students' attitudes toward patients with physical disabilities. We did not
      perform a meta-analysis because of the variation in instruments used and
      variables examined. We used a qualitative approach to identifying and reporting
      common findings across the studies. RESULTS: Results indicate that healthcare
      students and professionals have favorable attitudes toward persons with physical
      disabilities. More experience with persons with physical disabilities, both
      professionally and socially, was associated with more favorable attitudes. In
      addition, female healthcare students and professionals were found to have more
      positive attitudes toward patients with physical disabilities than do their male
      colleagues. Limited evidence exists examining the influence of age, race or
      ethnicity, and rank of student or professional on attitudes toward patients with
      physical disabilities. Finally, it was found that healthcare students and
      professionals reported overall more favorable attitudes than did individuals in
      non-healthcare professions. CONCLUSIONS: Overall, healthcare students' and
      professionals' attitudes toward persons with physical disabilities were
      favorable. However, some studies revealed the possibility that some healthcare
      providers demonstrate fear and anxiety with the challenge of caring for a patient
      with physical disabilities. Some of the factors associated with providers'
      attitudes toward patients with physical disabilities are potentially modifiable
      (e.g., experience) and could be the target of educational interventions to
      ameliorate this fear and facilitate higher quality care.

PMID- 22596077
TI  - Peripherally ethynylated carbazole-based core-modified porphyrins.
AB  - Peripherally ethynylated carbazole-based core-modified porphyrins were
      synthesized by sequential metal-catalyzed coupling and annulation reactions.
      Experimental results and DFT calculations both confirm that the pi-conjugated
      networks of the resulting porphyrins effectively delocalize over the entire
      macrocycle, including the ethynyl substituent groups.

PMID- 22596078
TI  - Radioprotective effects of Zingiber officinale Roscoe (ginger): past, present and
      future.
AB  - Radiation is an important modality in treating people with cancer especially when
      surgical intervention is impracticable or might debilitate the patient. However,
      effective use of ionizing radiation is compromised by the side effects that
      result from radiation-induced damage to normal tissue. The use of radioprotective
      compounds, which can selectively protect normal tissues against radiation injury
      is of immense use because in addition to association with protecting the normal
      tissue, it will also permits use of higher doses of radiation to obtain better
      cancer control and possible cure. However, till date no ideal radioprotectors are
      available as most synthetic compounds are toxic at their optimal concentrations.
      Plants commonly used as dietary and or therapeutic agents have recently been the
      focus of attention since in most cases they are non-toxic and are easily accepted
      for human use. Ginger, the rhizomes of Zingiber officinale Roscoe
      (Zingiberaceae), has widely been used as both culinary and medicinal agent.
      Preclinical studies carried out in the last decade has shown that ginger and its
      phytochemicals dehydrozingerone, zingerone possess radioprotective effects in
      laboratory animals and in cultured cells in vitro. The hydroalcoholic extract of
      ginger rhizome when administered either through intraperitoneal or oral route was
      effective in protecting against gamma radiation-induced sickness and mortality.
      The phytochemicals dehydrogingerone and zingerone present in ginger are also
      shown to protect mice against radiation-induced sickness and mortality.
      Mechanistic studies have indicated that the free radical scavenging, antioxidant
      affects, anti-inflammatory and anti-clastogenic effects may contribute towards
      the observed protection. Additionally, studies with tumor bearing mice have also
      shown that zingerone selectively protects the normal tissues against the
      tumoricidal effects of radiation. This review for the first time summarizes the
      results related to the radioprotective properties and also emphasizes the aspects
      that warrant future research to establish its activity and utility as a
      radioprotective agent.

PMID- 22596079
TI  - Self-reported fever and measured temperature in emergency department records used
      for syndromic surveillance.
AB  - Many public health agencies monitor population health using syndromic
      surveillance, generally employing information from emergency department (ED)
      visit records. When combined with other information, objective evidence of fever
      may enhance the accuracy with which surveillance systems detect syndromes of
      interest, such as influenza-like illness. This study found that patient chief
      complaint of self-reported fever was more readily available in ED records than
      measured temperature and that the majority of patients with an elevated
      temperature recorded also self-reported fever. Due to its currently limited
      availability, we conclude that measured temperature is likely to add little value
      to self-reported fever in syndromic surveillance for febrile illness using ED
      records.

PMID- 22596080
TI  - Male sex hormones and systemic inflammation in Alzheimer disease.
AB  - Several studies have shown that the levels of sex hormones in men with Alzheimer
      disease (AD) differ from men without AD. Therefore, male sex hormones have been
      postulated as risk modifiers in AD, possibly through immunomodulatory effects on
      known inflammatory AD risk factors, such as tumor necrosis factor alpha (TNF
      alpha). We conducted a cross-sectional study of sex hormones and TNF-alpha levels
      in 94 community-dwelling men with AD. Comparisons were made with normal values
      derived from the literature. Men with AD had lower free testosterone levels than
      non-AD men (1-sample t test: age <80, P=0.0002; age >=80, P<0.0001), and higher
      luteinizing hormone (LH) levels (Wilcoxon signed rank test: age <80, P=0.001; age
      >=80, P<0.0001). Within the cohort of men with AD, there was a positive
      correlation between LH and TNF-alpha (Spearman r=0.25, P=0.019), and this
      remained significant after correcting for age (partial r=0.21, P=0.05). These
      data support the hypothesis that sex hormones and the immune system influence
      each other in AD. Furthermore, modulatory effects between LH and TNF-alpha may
      provide a mechanism for an effect of male sex hormones on AD risk.

PMID- 22596081
TI  - Health care utilization and costs among patients with AD with and without
      dysphagia.
AB  - OBJECTIVE: To assess health care utilization and associated costs among patients
      with Alzheimer disease (AD), with and without dysphagia. METHODS: MarketScan
      Commercial and Medicare databases were analyzed. Patients with a diagnosis of AD
      with and without dysphagia between October 2006 and September 2010 were included.
      Acetylcholinesterase inhibitor usage, the number of outpatient and emergency room
      (ER) visits and hospitalizations, and associated health care costs were assessed.
      All variables were measured 1 year after the initial diagnosis of AD at the
      patient level. Patients with dysphagia were matched to patients without dysphagia
      using propensity score-matching (PSM) methods. Regression models were conducted
      to compare utilization and costs between the 2 groups. RESULTS: A total of 485
      patients with dysphagia and 8492 patients without dysphagia were included. Before
      matching, patients with dysphagia were older (81.1 vs. 79.8 y), and had higher
      Charlson Comorbidity Index scores (2.4 vs. 1.7). After matching, all baseline
      covariates were not statistically different between the 2 groups. Multivariate
      regression results showed that patients with dysphagia had a higher likelihood of
      all-cause hospitalizations [odds ratio (OR)=2.26, 95% confidence interval
      (CI)=1.70-2.99, P=0.001] and all-cause ER visits (OR=1.45, 95% CI=1.12-1.87,
      P=0.007) compared with patients without dysphagia; they also had a higher
      likelihood for AD-related hospitalizations and ER visits. The difference in all
      cause total health care, ER, and hospitalization costs between patients with and
      without dysphagia were $3620 (95% CI=$2863-$4375), $258 (95% CI=$241-$274), and
      $3547 (95% CI=$3325-$3770), respectively. CONCLUSIONS: This study suggests that
      patients with AD and dysphagia have higher health care utilization and costs
      compared with patients without dysphagia.

PMID- 22596082
TI  - Self-reference effect and autonoetic consciousness in Alzheimer disease: evidence
      for a persistent affective self in dementia patients.
AB  - Episodic memory deficits are predominately the first cognitive impairment in
      Alzheimer disease (AD). Previous studies have demonstrated that these deficits
      are specifically linked to autonoetic consciousness impairment, whereas noetic
      consciousness remains preserved in AD. This study focused on the self-reference
      effect and examined emotional valence, as it has been shown that emotional
      content can enhance memory in AD. A task involving recognition of emotional
      versus neutral adjective traits after self-reference versus semantic encoding,
      and using the Remember/Know/Guess paradigm was administered to 22 AD patients and
      18 normal controls. Results for AD patients show that self-reference increased
      autonoetic consciousness only for emotional and particularly negative trait
      adjectives. This interesting result indicates that neutral valence does not allow
      properties of the self to emerge in AD patients because of the progressive loss
      of the sense of self-linked to the disease, whereas emotional valence does.

PMID- 22596083
TI  - Improved conductivity reconstruction from multi-echo MREIT utilizing weighted
      voxel-specific signal-to-noise ratios.
AB  - Magnetic resonance electrical impedance tomography (MREIT) is a non-invasive
      method to visualize cross-sectional electrical conductivity and/or current
      density by measuring a magnetic flux density signal when an electrical current is
      injected into a subject. In the MREIT system, it is crucial to reduce the scan
      duration while maintaining spatial resolution and contrast for practical in vivo
      implementation. The purpose of the study is to optimize the measured magnetic
      flux density using an interleaved multiple-echo pulse sequence (injected current
      nonlinear encoding) that acquires each spatial position multiple times, although
      these pixels vary between echoes in their signal-to-noise ratio due to (a) T*2
      decay and (b) the current density passing through the pixel. Using the acquired
      multiple measured magnetic flux densities, the noise level for the measured
      magnetic flux density B(z) at each pixel is estimated using the relationship
      between the intensity of the magnitude and the width of the injected current. We
      determine an optimal combination of the multiply acquired magnetic flux
      densities, which optimally reduces the random noise artifacts. We develop a new
      denoising technique and apply it to a recovered conductivity distribution with a
      known noise level of the recovered magnetic flux density, which is designed to
      provide a stable internal conductivity distribution, while sustaining resolution.
      The proposed method uses three key steps: the first step is optimizing the
      magnetic flux density by using the multiple-echo magnetic flux densities at each
      pixel, the second step is estimating the noise level of this optimized magnetic
      flux density and the third step is applying a denoising technique using the pixel
      specific estimated noise level. Numerical simulation experiments using a three
      dimensional cylindrical phantom model validated the proposed method. Multiple
      echo B(z) data were generated, including in short T*2 or low spin-density
      regions, as a function of T*2 and the temporal extent of the injected current. In
      the simulation experiment, comparing between an equally averaged and the
      optimized B(z) methods, relative L2-mode errors were 0.053 and 0.024,
      respectively. In an actual imaging experiment of an agarose gel filled with
      objects of various conductivities and shapes, we acquired six echoes per
      repetition time. The optimal weighting factors minimized the effects of noise in
      B(z), and provided reconstructed conductivity maps that suppressed noise
      artifacts that normally accumulate in the low signal-to-noise-ratio defect
      regions.

PMID- 22596084
TI  - Palladium-catalyzed synthesis of 2-amino ketones from propargylic carbonates and
      secondary amines.
AB  - A novel palladium-catalyzed approach to 2-amino ketones from arylpropargylic
      carbonates bearing neutral, electron-rich, and electron-poor aromatic rings and
      cyclic secondary amines containing useful functional groups such as cyano,
      chloro, and bromo substituents has been developed.

PMID- 22596085
TI  - Reference electronic structure calculations in one dimension.
AB  - Large strongly correlated systems provide a challenge to modern electronic
      structure methods, because standard density functionals usually fail and
      traditional quantum chemical approaches are too demanding. The density-matrix
      renormalization group method, an extremely powerful tool for solving such
      systems, has recently been extended to handle long-range interactions on real
      space grids, but is most efficient in one dimension where it can provide
      essentially arbitrary accuracy. Such 1d systems therefore provide a theoretical
      laboratory for studying strong correlation and developing density functional
      approximations to handle strong correlation, if they mimic three-dimensional
      reality sufficiently closely. We demonstrate that this is the case, and provide
      reference data for exact and standard approximate methods, for future use in this
      area. 

PMID- 22596086
TI  - Hypericum androsaemum water extract inhibits proliferation in human colorectal
      cancer cells through effects on MAP kinases and PI3K/Akt pathway.
AB  - MAP kinase and PI3K/Akt signalling pathways are commonly altered in colorectal
      carcinoma (CRC) leading to tumor growth due to increased cell proliferation and
      inhibition of apoptosis. Several species of the genus Hypericum are used in
      Portugal to prepare herbal teas to which digestive tract effects are attributed.
      In the present study, the antiproliferative and proapoptotic effects of the water
      extracts of H. androsaemum (HA) and H. perforatum (HP) were investigated in two
      human colon carcinoma-derived cell lines, HCT15 and CO115, which harbour
      activating mutations of KRAS and BRAF, respectively. Contrarily to HP, HA
      significantly inhibited cell proliferation and induced apoptosis in both cell
      lines. HA decreased BRAF and phospho-ERK expressions in CO115, but not in HCT15.
      HA also decreased Akt phosphorylation in CO115 and induced p38 and JNK in both
      cell lines. HA induced cell cycle arrest at S and G2/M phases as well as caspase
      dependent apoptosis in both cell lines. Chlorogenic acid (CA), the main phenolic
      compound present in the HA extract and less represented in the HP water extract,
      did, however, not show any of those effects when used individually. In
      conclusion, water extract of HA, but not of HP, controlled CRC proliferation and
      specifically acted on mutant and not wild-type BRAF. The effect of HA was,
      however, not due to CA alone.

PMID- 22596087
TI  - Development, implementation, and evaluation of an institutional daily awakening
      and spontaneous breathing trial protocol: a quality improvement project.
AB  - INTRODUCTION: While one controlled trial found that a daily awakening and
      spontaneous breathing trial (DA-SBT) decreases time on mechanical ventilation
      (MV), there is a paucity of real-world data surrounding the development,
      implementation, and impact of DA-SBT protocols. We describe a multidisciplinary
      process improvement effort in 2, 10-bed medical intensive care units (MICUs) at a
      330-bed academic medical center that focused on the development, implementation,
      and evaluation of a new DA-SBT protocol. METHODS: A DA-SBT protocol, developed
      using results from a nursing survey literature and available institutional
      resources, was implemented after extensive clinician education and institution of
      quality reminders to boost use. Postprotocol compliance was evaluated. Use of
      sedation, DA and SBT practices, and clinical outcomes were retrospectively
      compared between the before and after DA-SBT protocol groups (ie, consecutive
      MICU patients requiring a continuously infused sedative [CIS] >=24 hours).
      RESULTS: In the after group (n = 32), the DA and SBT compliances were 44% and
      84%, respectively. Compared with the before group (n = 33), after group patients
      received CIS on fewer days of MV (100% vs 67%, P = .003) and had their CIS down
      titrated by >=25% on more days of CIS (40% vs 71%, P = .006). Neither total CIS
      dose (P = .49), total MV days (P = .75), days of MV where a SBT occurred (P =
      .38), nor episodes of self-extubation (15% vs 6%, P = .43) differed between the 2
      groups. CONCLUSION: Despite the implementation of a DA-SBT protocol that was
      individualized to clinician preferences and institutional resources and
      accompanied by substantial education and reminders for use, compliance to the DA
      component of this protocol was low and duration of MV remained unchanged.
      Additional quality improvement strategies are needed to overcome barriers to DA
      SBT protocol use that may not exist in controlled clinical trials.

PMID- 22596088
TI  - Effect of the 2009 influenza A/H1N1 pandemic on viral respiratory infections in
      the first year of life.
AB  - BACKGROUND: The effect of the 2009 H1N1 influenza pandemic on viral epidemiology
      of upper and lower respiratory tract infections (URI and LRI) in healthy infants
      in the first year of life has not been well studied. METHODS: A total of 180
      healthy infants were enrolled from birth and monitored for occurrences of URI,
      LRI and acute otitis media complications until the first acute otitis media
      episode or between 6 and 12 months of age. Nasopharyngeal specimens collected
      during acute respiratory illnesses were tested for 18 viruses. RESULTS: Between
      October 2008 and April 2011, 373 URI episodes, including 20 with LRI, in 139
      infants were documented. Viral studies were performed on 189 URI episodes; 87%
      were positive. Throughout the 31-month period (1386 patient-months), rhinovirus
      was the predominant virus causing URI (55%); respiratory syncytial virus was the
      major cause of LRI (64%). Although there was a significant increase in parent
      initiated visit rate during the 15-month influenza pandemic as compared with
      prepandemic and postpandemic periods, only 4 cases of influenza were detected (2
      cases during and 2 cases prepandemic and postpandemic). CONCLUSIONS: The 2009
      influenza A/H1N1 pandemic had no impact on the overall viral epidemiology of
      respiratory infections in healthy infants in the first year of life but resulted
      in increased parent-initiated visits due to respiratory symptoms. Maternal
      antibody and absence of comorbidity may explain the low influenza burden whereas
      parental anxiety may explain the increased healthcare visit rate during the
      pandemic.

PMID- 22596089
TI  - Activation of nuclear inositide signalling pathways during erythropoietin therapy
      in low-risk MDS patients.
AB  - Inositide signaling pathways can have a role in the Myelodysplastic Syndromes
      (MDS) progression to acute myeloid leukemia. Erythropoietin (EPO) is currently
      used in low-risk MDS, where it successfully corrects anemia in 50-70% of
      patients. However, some MDS patients are refractory to this treatment and little
      is known about the exact molecular mechanisms underlying the effect of EPO in
      these subjects. Here, we investigated the role of inositide pathways in low-risk
      MDS treated with EPO, mainly focusing on the Akt/PI-PLC (Phosphoinositide
      Phospholipase C) gamma1 axis, which is activated by the EPO receptor, and PI
      PLCbeta1/Cyclin D3 signaling, as Cyclin D3 is associated with hematopoietic
      proliferation and differentiation. Interestingly, EPO responder patients showed a
      specific activation of both the Akt/PI-PLCgamma1 pathway and beta-Globin gene
      expression, while nonresponders displayed an increase in PI-PLCbeta1 signaling.
      Moreover, in normal CD34+ cells induced to erythroid differentiation, PI-PLCbeta1
      overexpression abrogated both EPO-induced Akt phosphorylation and beta-Globin
      expression. Overall, these findings suggest that PI-PLCbeta1 can act as a
      negative regulator of erythroid differentiation and confirm the involvement of
      Akt/PI-PLCgamma1 pathway in EPO signaling, therefore contributing to the
      comprehension of the effect of EPO in low-risk MDS and possibly paving the way to
      the identification of MDS patients at higher risk of refractoriness to EPO
      treatment.

PMID- 22596090
TI  - Chebyshev high-dimensional model representation (Chebyshev-HDMR) potentials:
      application to reactive scattering of H2 from Pt(111) and Cu(111) surfaces.
AB  - Gas phase and surface reactions involving polyatomic molecules are of central
      importance to chemical physics, and require accurately fit potential energy
      surfaces describing the interaction in their systems. Here, we propose a method
      for generating a High Dimensional Model Representation (HDMR) of a
      multidimensional potential energy surface (PES) and apply it to reactive molecule
      surface scattering problems. In the HDMR treatment, all N degrees of freedom
      (DOF) of an N-dimensional PES are represented but only n < N are explicitly
      coupled. The HDMR is obtained from Chebyshev polynomial expansions for each
      degree of freedom, where expansion coefficients are efficiently evaluated using
      discrete cosine transform (DCT) algorithms and properties of Chebyshev
      polynomials. HDMR surfaces constructed for the reactive scattering of H2 from
      Pt(111) and Cu(111) are used in quantum dynamics simulations; the resultant state
      resolved reaction and scattering probabilities are compared to those from
      simulations using full (6D) PESs and n-mode PESs from previous work. The results
      are encouraging, and suggest that this method may be applicable to "late barrier"
      reactive systems for which the previously-used n-mode representation fails. 

PMID- 22596092
TI  - Comment on 'Plastic scintillation dosimetry: comparison of three solutions for
      the Cerenkov challenge'.

PMID- 22596091
TI  - Ultra-rapid laser protein micropatterning: screening for directed polarization of
      single neurons.
AB  - Protein micropatterning is a powerful tool for studying the effects of
      extracellular signals on cell development and regeneration. Laser micropatterning
      of proteins is the most flexible method for patterning many different geometries,
      protein densities, and concentration gradients. Despite these advantages, laser
      micropatterning remains prohibitively slow for most applications. Here, we take
      advantage of the rapid multi-photon induced photobleaching of fluorophores to
      generate sub-micron resolution patterns of full-length proteins on polymer
      monolayers, with sub-microsecond exposure times, i.e. one to five orders of
      magnitude faster than all previous laser micropatterning methods. We screened a
      range of different PEG monolayer coupling chemistries, chain-lengths and
      functional caps, and found that long-chain acrylated PEG monolayers are effective
      at resisting non-specific protein adhesion, while permitting efficient cross
      linking of biotin-4-fluorescein to the PEG monolayers upon exposure to
      femtosecond laser pulses. We find evidence that the dominant photopatterning
      chemistry switches from a two-photon process to three- and four-photon absorption
      processes as the laser intensity increases, generating increasingly volatile
      excited triplet-state fluorophores, leading to faster patterning. Using this
      technology, we were able to generate over a hundred thousand protein patterns
      with varying geometries and protein densities to direct the polarization of
      hippocampal neurons with single-cell precision. We found that certain arrays of
      patterned triangles as small as neurite growth cones can direct polarization by
      impeding the elongation of reverse-projecting neurites, while permitting
      elongation of forward-projecting neurites. The ability to rapidly generate and
      screen such protein micropatterns can enable discovery of conditions necessary to
      create in vitro neural networks with single-neuron precision for basic discovery,
      drug screening, as well as for tissue scaffolding in therapeutics.

PMID- 22596093
TI  - Solid-phase synthesis and acidolytic degradation of sterically congested
      oligoether dendrons.
AB  - Up to third-generation sterically crowded polyether dendrons were prepared on a
      solid support, using a novel building block derived from dimethyl 5
      hydroxyisophthalate via O-allylation/Claisen rearrangement key steps. These
      dendrons underwent smooth disassembly to monomers, when subjected to acidic
      solution. The reason for this decomposition was traced to the increased electron
      density of the aromatic rings of the new monomers that destabilizes the bonds
      connecting the building blocks.

PMID- 22596094
TI  - Climate warming could shift the timing of seed germination in alpine plants.
AB  - BACKGROUND AND AIMS: Despite the considerable number of studies on the impacts of
      climate change on alpine plants, there have been few attempts to investigate its
      effect on regeneration. Recruitment from seeds is a key event in the life-history
      of plants, affecting their spread and evolution and seasonal changes in climate
      will inevitably affect recruitment success. Here, an investigation was made of
      how climate change will affect the timing and the level of germination in eight
      alpine species of the glacier foreland. METHODS: Using a novel approach which
      considered the altitudinal variation of temperature as a surrogate for future
      climate scenarios, seeds were exposed to 12 different cycles of simulated
      seasonal temperatures in the laboratory, derived from measurements at the soil
      surface at the study site. KEY RESULTS: Under present climatic conditions,
      germination occurred in spring, in all but one species, after seeds had
      experienced autumn and winter seasons. However, autumn warming resulted in a
      significant increase in germination in all but two species. In contrast, seed
      germination was less sensitive to changes in spring and/or winter temperatures,
      which affected only three species. CONCLUSIONS: Climate warming will lead to a
      shift from spring to autumn emergence but the extent of this change across
      species will be driven by seed dormancy status. Ungerminated seeds at the end of
      autumn will be exposed to shorter winter seasons and lower spring temperatures in
      a future, warmer climate, but these changes will only have a minor impact on
      germination. The extent to which climate change will be detrimental to
      regeneration from seed is less likely to be due to a significant negative effect
      on germination per se, but rather to seedling emergence in seasons that the
      species are not adapted to experience. Emergence in autumn could have major
      implications for species currently adapted to emerge in spring.

PMID- 22596095
TI  - Mechanisms of metal ion-coupled electron transfer.
AB  - Redox inactive metal ions acting as Lewis acids can control electron transfer
      from electron donors (D) to electron acceptors (A) by binding to radical anions
      of electron acceptors which act as Lewis bases. Such electron transfer is defined
      as metal ion-coupled electron transfer (MCET). Mechanisms of metal ion-coupled
      electron transfer are classified mainly into two pathways, i.e., metal ion
      binding to electron acceptors followed by electron transfer (MB/ET) and electron
      transfer followed by metal ion binding to the resulting radical anions of
      electron acceptors (ET/MB). In the former case, electron transfer and the
      stronger binding of metal ions to the radical anions occur in a concerted manner.
      Examples are shown in each case to clarify the factors to control MCET reactions
      in both thermal and photoinduced electron-transfer reactions including back
      electron-transfer reactions. 

PMID- 22596097
TI  - Removal of a bullet in the pericardial cavity by video-assisted thoracoscopic
      surgery.
AB  - The use of video-assisted thoracoscopic surgery (VATS) in dealing with thoracic
      trauma has been well established. VATS avoids a thoracotomy and offers excellent
      visualization of the entire pleural cavity. The removal of bullets from the
      pleural cavity using VATS has also been reported, but, to our knowledge, this is
      the first time a bullet has been removed from the pericardial cavity using VATS.

PMID- 22596096
TI  - Aggregate risk score for predicting mortality after surgical biopsy for
      interstitial lung disease.
AB  - In order to develop a practical risk score for 90-day mortality following
      surgical lung biopsy (SLB) for interstitial lung disease (ILD) we reviewed 311
      consecutive patients undergoing SLB for ILD between 2002 and 2009. Postoperative
      complication, 30-day and 90-day mortality rates were 11.5%, 9% and 10.6%
      respectively. Univariable and multivariable analyses, validated by bootstrap
      statistics, were used to identify factors associated with 90-day mortality. A
      scoring system was developed by proportionally weighting the regression
      coefficients of the significant predictors of 90-day mortality: age >67 (P <
      0.0001, weighted score 1.5), preoperative intensive care unit (ICU) admission (P
      = 0.006, weighted score 2), immunosuppressive treatment (P = 0.004, weighted
      score 1.5) and open surgery (P = 0.03, weighted score 1). Patients were grouped
      in four classes showing incremental risk of death at 90 days: class A, score 0
      (2%); class B, score 1-2 (12%); class C, score 2.5-3 (40%); class D, score >3
      (86%); P <0.0001). SLB entails a considerable surgical risk with an overall 90
      day mortality around 10%. We were able to develop a practical risk score which,
      if validated by other independent studies, can be easily used to stratify the
      risk of SLB candidates and assess the cost-effectiveness of this procedure.

PMID- 22596098
TI  - A novel quadraport needle with improved intravitreal drug dispersion.

PMID- 22596099
TI  - Long-term surgical outcomes after vitrectomy for symptomatic lamellar macular
      holes.
AB  - PURPOSE: To determine long-term surgical findings and outcomes after vitrectomy
      for symptomatic lamellar macular holes. METHODS: This is a retrospective,
      consecutive, interventional case series. Sixteen patients (31 eyes) with lamellar
      macular holes and central visual loss participated in the study. All patients
      underwent 3-port pars plana vitrectomy with membranectomy and/or internal
      limiting membrane peeling and gas tamponade under the care of one author. Best
      corrected visual acuity and optical coherence tomography appearance were
      determined preoperatively and postoperatively. RESULTS: Final visual acuity
      improved more than 2 lines postoperatively in 18 eyes (58.1%) and decreased in 2
      eyes (6.5%) leading to a mean gain of 0.18 logarithm of the minimum angle of
      resolution visual acuity during the mean follow-up period of 39 +/- 24 months (12
      85 months). Twenty-eight eyes (90.3%) improved or normalized in foveal appearance
      on postoperative optical coherence tomography images of the macula, 1 eye
      remained unchanged, and 1 eye (3.2%) had chronic cystoid macular edema, 1 eye was
      unchanged, and 1 eye showed recurrence of lamellar macular hole. CONCLUSION: In
      patients with central visual loss from lamellar macular holes, vitrectomy,
      membranectomy, and/or internal limiting membrane peeling and gas tamponade appear
      to have a beneficial effect for a mean of 3 years.

PMID- 22596100
TI  - Consensus statement on the pathology of IgG4-related disease.
AB  - IgG4-related disease is a newly recognized fibro-inflammatory condition
      characterized by several features: a tendency to form tumefactive lesions in
      multiple sites; a characteristic histopathological appearance; and-often but not
      always-elevated serum IgG4 concentrations. An international symposium on IgG4
      related disease was held in Boston, MA, on 4-7 October 2011. The organizing
      committee comprising 35 IgG4-related disease experts from Japan, Korea, Hong
      Kong, the United Kingdom, Germany, Italy, Holland, Canada, and the United States,
      including the clinicians, pathologists, radiologists, and basic scientists. This
      group represents broad subspecialty expertise in pathology, rheumatology,
      gastroenterology, allergy, immunology, nephrology, pulmonary medicine, oncology,
      ophthalmology, and surgery. The histopathology of IgG4-related disease was a
      specific focus of the international symposium. The primary purpose of this
      statement is to provide practicing pathologists with a set of guidelines for the
      diagnosis of IgG4-related disease. The diagnosis of IgG4-related disease rests on
      the combined presence of the characteristic histopathological appearance and
      increased numbers of IgG4+ plasma cells. The critical histopathological features
      are a dense lymphoplasmacytic infiltrate, a storiform pattern of fibrosis, and
      obliterative phlebitis. We propose a terminology scheme for the diagnosis of IgG4
      related disease that is based primarily on the morphological appearance on
      biopsy. Tissue IgG4 counts and IgG4:IgG ratios are secondary in importance. The
      guidelines proposed in this statement do not supplant careful clinicopathological
      correlation and sound clinical judgment. As the spectrum of this disease
      continues to expand, we advocate the use of strict criteria for accepting newly
      proposed entities or sites as components of the IgG4-related disease spectrum.

PMID- 22596101
TI  - Partial p16 staining in oropharyngeal squamous cell carcinoma: extent and pattern
      correlate with human papillomavirus RNA status.
AB  - Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma has
      unique biology and better outcomes. p16 immunostaining is used as a surrogate
      marker for transcriptionally active HPV. Although diffuse staining is generally
      accepted as positive, the significance of partial staining has not been
      established, nor has the cutoff for extent of p16 staining that should be used to
      identify a tumor as HPV-related. From three other large studies utilizing p16
      immunohistochemistry, we identified all cases with partial positive staining. The
      p16-stained slides were reviewed by three study pathologists for staining
      (nuclear and cytoplasmic) extent (in quartiles), and also for percentage that was
      confluent (ie, back-to-back cell staining). Tumors were histologically typed
      (keratinizing, non-keratinizing, or non-keratinizing with maturation) and tested
      for high-risk HPV by RNA in-situ hybridization and reverse-transcriptase PCR. For
      the 16 cases, there were two 4+(13%), five 3+(31%), six 2+(38%), and three
      1+(19%) p16 staining tumors. Extent of staining ranged from 5 to 90% of cells
      positive with 25% or more confluent staining in 4/16 (25%). Of the 16 (31%)
      cases, 5 were HPV-related on the basis of RNA in-situ hybridization and reverse
      transcriptase PCR. All of these cases had >50% p16 staining, 4/5 (80%) had more
      than 25% confluent staining, and 4/7 (57%) had non-keratinizing histological
      features. Only one of the p16 1+/2+ tumors was HPV RNA-positive (by reverse
      transcriptase PCR only and low level). All 1+/2+ cases were keratinizing type or
      undifferentiated. By sensitive detection methods, most partial p16-positive
      squamous cell carcinoma cases with >50% staining harbor transcriptionally active
      HPV, and most HPV+ tumors have significant amounts of confluent staining. Cases
      with <50% p16 staining and lacking significant confluent staining rarely harbor
      HPV. These results support that greater than 75% p16 staining or, alternatively,
      >50% staining combined with >25% confluent areas, are suitable cutoffs for
      defining positivity.

PMID- 22596103
TI  - Are lithium and sodium salts of N-(2-hydroxyphenyl)-salicylaldimine aromatic
      metalla-hetero[10]annulenes? An answer given by spatial magnetic properties
      (through space NMR shieldings-TSNMRS).
AB  - The spatial magnetic properties (through space NMR shieldings-TSNMRS) of the enol
      tautomer of N-(2-hydroxyphenyl)-salicylaldimine, the lithium and sodium salts in
      comparison with cyclodecapentaene and pyrano[2,3-b]pyrrole were studied to answer
      this question. 

PMID- 22596102
TI  - Localization of propionibacterium acnes in granulomas supports a possible
      etiologic link between sarcoidosis and the bacterium.
AB  - Sarcoidosis likely results from the exposure of a genetically susceptible subject
      to an environmental agent, possibly an infectious one. Mycobacterial and
      propionibacterial organisms are the most commonly implicated potential etiologic
      agents. Propionibacterium acnes is the only microorganism, however, found in
      sarcoid lesions by bacterial culture. To evaluate the pathogenic role of this
      indigenous bacterium, we screened for the bacterium in sarcoid and non-sarcoid
      tissues using immunohistochemical methods with novel P. acnes-specific monoclonal
      antibodies that react with cell-membrane-bound lipoteichoic acid (PAB antibody)
      and ribosome-bound trigger-factor protein (TIG antibody). We examined formalin
      fixed and paraffin-embedded samples of lungs and lymph nodes from 196 patients
      with sarcoidosis, and corresponding control samples from 275 patients with non
      sarcoidosis diseases. The samples were mostly from Japanese patients, with 64
      lymph node samples from German patients. Immunohistochemistry with PAB antibody
      revealed small round bodies within sarcoid granulomas in 20/27 (74%) video
      assisted thoracic surgery lung samples, 24/50 (48%) transbronchial lung biopsy
      samples, 71/81 (88%) Japanese lymph node samples, and 34/38 (89%) German lymph
      node samples. PAB antibody did not react with non-sarcoid granulomas in any of
      the 45 tuberculosis samples or the 34 samples with sarcoid reaction. In
      nongranulomatous areas, small round bodies detected by PAB antibody were found in
      alveolar macrophages of lungs and paracortical macrophages of lymph nodes from
      many sarcoid and some non-sarcoid patients. Large-spheroidal acid-fast bodies,
      Hamazaki-Wesenberg bodies, which were found in 50% of sarcoid and 15% of non
      sarcoid lymph node samples, reacted with both PAB and TIG antibodies. Electron
      microscopy revealed that these Hamazaki-Wesenberg bodies had a single bacterial
      structure and lacked a cell wall with occasional protrusions from the body. The
      high frequency and specificity of P. acnes, detected by PAB antibody within
      sarcoid granulomas, indicates that this indigenous bacterium might be the cause
      of granuloma formation in many sarcoid patients.

PMID- 22596104
TI  - Recent progress in the design of nanofiber-based biosensing devices.
AB  - This review addresses recent progress made in the use of nanofibers for analyte
      detection and sample preparation within analytical devices. The unique
      characteristics of nanofibers make them ideal for incorporation within sensors
      designed to allow for sensitive detection of clinical, environmental, and food
      safety analytes. In particular, the extremely large surface area provided by
      nanofiber mats and arrays drastically increases the availability of
      immobilization sites within biosensors. Additionally, nanofibers can be made from
      a variety of biocompatible materials and can be functionalized through the
      incorporation of nanoscale materials within spinning dopes or polymerization
      solutions. Finally, methods of nanofiber formation are largely well understood,
      allowing for controlled synthesis of nanofiber mats with specific sizes, shapes,
      pore sizes, and tensile strengths. In this paper, we present a survey of the
      different materials that are currently being used to produce nanofibers for use
      within sensing devices. In addition, we compare the limits of detection and
      linear ranges of nanofiber-based sensors and conventional sensors to determine if
      detection is improved by the inclusion of nanoscale materials.

PMID- 22596106
TI  - Kasha or state selective behavior in the photochemistry of ortho
      nitrobenzaldehyde?
AB  - The photochemistry of ortho-nitrobenzaldehyde dissolved in tetrahydrofuran was
      studied by means of femtosecond UV/Vis and IR spectroscopy. Comparison was made
      of the spectral and temporal signatures for ~400 nm and ~260 nm excitation. The
      400 nm excitation promotes NBA to its lowest excited singlet state of npi*
      character whereas for 260 nm an upper excited state of pipi* character is
      addressed. On the picosecond time scale, the molecule undergoes hydrogen
      transfer, yielding a ketene intermediate, internal conversion recovering the
      starting material, and intersystem crossing. Time constants and yields of these
      processes are virtually not affected by the excitation wavelength. For 400 nm
      excitation a ~100 fs decay component seen in the 260 nm experiment is absent,
      indicating that this component is due to a pipi* -> npi* internal conversion. In
      contrast to its formation, the decay of the ketene intermediate is influenced by
      the excitation wavelength. This can be attributed to different amounts of
      vibrational excitation.

PMID- 22596107
TI  - The role of NMDA receptors in human eating behavior: evidence from a case of anti
      NMDA receptor encephalitis.
AB  - Research in animal models has implicated N-methyl-D-aspartate (NMDA) receptors
      (NMDARs) in the control of food intake. Until now, these findings have been not
      replicated in humans. Here we describe a 22-year-old woman with anti-NMDAR
      encephalitis and no prior neurological or psychiatric history. Her clinical
      course was marked by successive eating disorders: anorexia followed by
      hyperphagia. We propose that, much as they do in other animals, NMDARs in humans
      interact with the neuroendocrine, homeostatic, and reward systems controlling
      food intake in the central and peripheral nervous system structures related to
      feeding and satiety.

PMID- 22596108
TI  - Line copying:  distinct "where" and "aiming" spatial bias in healthy adults.
AB  - BACKGROUND: Spatial bias in natural, implicit tasks such as reaching and grasping
      may manifest differently from that in arbitrary laboratory-experiment line
      bisection tasks. Because spatial processing in everyday activities is difficult
      to quantify, it is important to study spatial behavior in an implicit laboratory
      task. Drawing tasks of copying lines or objects integrate spatial perceptual
      attentional ("where") input and motor-intentional ("aiming") output, and may be
      more implicit than line bisection because participants are unaware that the
      placement of their drawings will be assessed. OBJECTIVES: We examined whether it
      is possible to distinguish "where" and "aiming" spatial biases in a line-copying
      task. We examined changes in "where" and "aiming" biases in response to bottom-up
      versus top-down cues (hemispace presentation and drawing direction). METHODS: In
      13 healthy adults, we collected copied-line displacements and lengths in both the
      natural (left-right congruency) and reversed (left-right incongruency) viewing
      conditions, to distinguish "where" and "aiming" biases. RESULTS: Participants
      displaced lines leftward (P=0.01) as they copied, displaying primarily a "where"
      bias. They displaced lines in the drawing direction irrespective of viewing
      condition, a finding consistent with induced "aiming" effects (P=0.291).
      Presenting lines on participants' right or left side did not affect the "where"
      spatial bias. Cues did not affect copied-line lengths. CONCLUSIONS: We showed
      that an implicit laboratory-experiment task of copying lines can discern complex
      stages of spatial processing in healthy adults. Further evaluation of this task
      will greatly contribute to the understanding of mechanisms of human spatial
      cognition.

PMID- 22596109
TI  - The effect of ropinirole on apathy and depression after herpes encephalitis.
AB  - We describe a 76-year-old man with herpes encephalitis whose symptom of severe
      apathy was improved by the dopamine D2/D3 receptor agonist ropinirole. Brain
      magnetic resonance imaging had shown lesions in the patient's right mesial
      temporal cortex, right insula, and bilateral medial frontal regions. During
      treatment with acyclovir, he had developed severe apathy and depression. On
      neuropsychological assessment, he scored 21/30 points on the Mini-Mental State
      Examination, 30/42 on the Starkstein Apathy Scale (cutoff score =16), and 59/80
      on the Zung Self-Rating Depression Scale (cutoff score=40). We then started him
      on ropinirole 0.25 mg/day. Over the next 10 days, his apathy and depression
      gradually improved. On day 10 of treatment, follow-up testing showed that his
      Apathy Scale score had improved to 25 points. This case suggests that a low dose
      of a dopamine receptor agonist may be an effective treatment for patients who
      develop apathy and depression after encephalitis.

PMID- 22596110
TI  - Long-term outcome of cognitive functions, emotional behavior, and quality of life
      in a family with familial hemiplegic migraine.
AB  - OBJECTIVE: To investigate long-term cognitive outcome, mood, and quality of life
      in a family with genetically proven familial hemiplegic migraine (FHM).
      BACKGROUND: FHM is a rare autosomal-dominant subtype of migraine with aura,
      characterized by some degree of hemiparesis during the aura. In a previous study,
      we showed preserved and impaired cognitive functions in patients with FHM. Until
      now, the progression of cognitive dysfunctions has not been known. However, the
      ability to predict progression is important for counseling patients about
      education, career, and family life. METHODS: Seven years after extensive baseline
      neuropsychological testing, we retested 6 members of a family with FHM, including
      questionnaires about mood and quality of life. RESULTS: The follow-up assessment
      revealed no global cognitive decline. All the patients' linguistic abilities and
      verbal memory remained intact; however, their figural memory, attention, and some
      aspects of executive function were impaired. Half the patients had a slight
      deterioration in their visuoconstructional functions. Half had higher scores on
      the trait and state anxiety measures. CONCLUSIONS: Cognitive deficits in a family
      with FHM persisted, but without marked progression. Worsening of
      visuoconstructional abilities may be related to executive dysfunction, confirming
      a disturbance of cerebrocerebellar circuits.

PMID- 22596111
TI  - Dysexecutive syndrome:  a specific pattern of cognitive impairment in systemic
      sclerosis.
AB  - BACKGROUND AND PURPOSE: Systemic sclerosis (SSc) is a connective-tissue disorder
      characterized by microvascular damage and tissue fibrosis. Although overt nervous
      system involvement is unusual in SSc, imaging studies have shown cerebral
      hypoperfusion. We evaluated cognitive functions in patients with SSc who had no
      history of neurological involvement, to seek cognitive impairment caused by the
      suggested cerebral hypoperfusion. METHODS: We performed a comprehensive
      neuropsychological test battery on 31 patients with SSc and on 2 groups of age
      adjusted, sex-adjusted, and education-adjusted controls: 15 patients with
      rheumatoid arthritis and 20 healthy volunteers. RESULTS: The patients with SSc
      scored significantly worse on most of the measures of executive function than the
      2 control groups (P<0.05). However, both patient groups did worse than the
      healthy controls on measures of attention and memory (P<0.005). CONCLUSIONS: Our
      results suggest that patients with SSc have a specific pattern of cognitive
      impairment: the dysexecutive syndrome. Attentional and memory problems, however,
      may arise from other confounders such as disease duration and chronic medication
      use. SSc may be a rare cause of vascular cognitive impairment.

PMID- 22596112
TI  - Normative data for healthy middle-aged and elderly performance on the Addenbrooke
      Cognitive Examination-Revised.
AB  - OBJECTIVE: To provide normative data for healthy middle-aged and elderly
      Brazilians' performance on the Addenbrooke Cognitive Examination-Revised (ACE-R)
      and to investigate the effects of age, sex, and schooling on test performance.
      BACKGROUND: The ACE-R is a brief cognitive battery that assesses various aspects
      of cognition. Its 5 subdomains (Attention and Orientation, Memory, Verbal
      Fluency, Language, and Visuospatial Abilities) are commonly impaired in Alzheimer
      disease or frontotemporal dementia. METHODS: We evaluated 144 cognitively healthy
      volunteers (50% men, 50% women) aged 50 to 93 years, with 4 to 24 years of
      schooling. We divided the participants into 4 age groups, each of which was then
      stratified into 3 groups according to years of education. We assessed all
      participants with the ACE-R, the Mattis Dementia Rating Scale, and the Cornell
      Scale for Depression in Dementia. RESULTS: Years of education affected all ACE-R
      subscores. Age influenced the Verbal Fluency subscore (P<0.001) and the ACE-R
      total score (P<0.05). Sex affected the Attention and Orientation (P=0.037) and
      Mini-Mental State Examination subscores (P=0.048), but not the ACE-R total score
      (P>0.05). CONCLUSIONS: The performance of healthy middle-aged and elderly
      individuals on the ACE-R battery is strongly influenced by education and, to a
      lesser extent, by age. These findings are of special relevance in countries with
      populations that have marked heterogeneity in educational levels.

PMID- 22596113
TI  - Misplaced childhood.

PMID- 22596114
TI  - Needless conflict.

PMID- 22596115
TI  - Honest opinions.

PMID- 22596116
TI  - Reach out to defend evolution.

PMID- 22596128
TI  - Child-study turmoil leaves bitter taste.

PMID- 22596130
TI  - Messages from the early Universe.

PMID- 22596129
TI  - Plagiarism charge for Romanian minister.

PMID- 22596131
TI  - Malaria surge feared.

PMID- 22596132
TI  - EU agencies accused of conflicts of interest.

PMID- 22596134
TI  - Go West, young Russian.

PMID- 22596135
TI  - Rise of the coyote: The new top dog.

PMID- 22596136
TI  - Replication studies: Bad copy.

PMID- 22596137
TI  - Science policy: Beyond the great and good.

PMID- 22596138
TI  - Transit of Venus: Last chance to see.

PMID- 22596143
TI  - Particle physics: Don't let furore over neutrinos blur results.

PMID- 22596144
TI  - Drug discovery: In defence of the animal model.

PMID- 22596145
TI  - Ecology: Preserve Brazil's aquatic biodiversity.

PMID- 22596146
TI  - Sociology: The social sciences are already relevant.

PMID- 22596147
TI  - Environment: Control electronic waste in India.

PMID- 22596148
TI  - Planetary science: Martian sand blowing in the wind.

PMID- 22596149
TI  - Atomic physics: Electrons get real.

PMID- 22596150
TI  - Structural biology: How opioid drugs bind to receptors.

PMID- 22596151
TI  - Neuroscience: Brain-controlled robot grabs attention.

PMID- 22596152
TI  - Genetics: Fish heads and human disease.

PMID- 22596153
TI  - Earth science: Geomagnetism under scrutiny.

PMID- 22596156
TI  - Earth-like sand fluxes on Mars.
AB  - Strong and sustained winds on Mars have been considered rare, on the basis of
      surface meteorology measurements and global circulation models, raising the
      question of whether the abundant dunes and evidence for wind erosion seen on the
      planet are a current process. Recent studies showed sand activity, but could not
      determine whether entire dunes were moving--implying large sand fluxes--or
      whether more localized and surficial changes had occurred. Here we present
      measurements of the migration rate of sand ripples and dune lee fronts at the
      Nili Patera dune field. We show that the dunes are near steady state, with their
      entire volumes composed of mobile sand. The dunes have unexpectedly high sand
      fluxes, similar, for example, to those in Victoria Valley, Antarctica, implying
      that rates of landscape modification on Mars and Earth are similar.

PMID- 22596155
TI  - Cardiac angiogenic imbalance leads to peripartum cardiomyopathy.
AB  - Peripartum cardiomyopathy (PPCM) is an often fatal disease that affects pregnant
      women who are near delivery, and it occurs more frequently in women with pre
      eclampsia and/or multiple gestation. The aetiology of PPCM, and why it is
      associated with pre-eclampsia, remain unknown. Here we show that PPCM is
      associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia.
      Mice that lack cardiac PGC-1alpha, a powerful regulator of angiogenesis, develop
      profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic
      therapies. In humans, the placenta in late gestation secretes VEGF inhibitors
      like soluble FLT1 (sFLT1), and this is accentuated by multiple gestation and pre
      eclampsia. This anti-angiogenic environment is accompanied by subclinical cardiac
      dysfunction, the extent of which correlates with circulating levels of sFLT1.
      Exogenous sFLT1 alone caused diastolic dysfunction in wild-type mice, and
      profound systolic dysfunction in mice lacking cardiac PGC-1alpha. Finally, plasma
      samples from women with PPCM contained abnormally high levels of sFLT1. These
      data indicate that PPCM is mainly a vascular disease, caused by excess anti
      angiogenic signalling in the peripartum period. The data also explain how late
      pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and
      multiple gestation are important risk factors for the development of PPCM.

PMID- 22596157
TI  - Resolving the time when an electron exits a tunnelling barrier.
AB  - The tunnelling of a particle through a barrier is one of the most fundamental and
      ubiquitous quantum processes. When induced by an intense laser field, electron
      tunnelling from atoms and molecules initiates a broad range of phenomena such as
      the generation of attosecond pulses, laser-induced electron diffraction and
      holography. These processes evolve on the attosecond timescale (1 attosecond = 1
      as = 10(-18) seconds) and are well suited to the investigation of a general issue
      much debated since the early days of quantum mechanics--the link between the
      tunnelling of an electron through a barrier and its dynamics outside the barrier.
      Previous experiments have measured tunnelling rates with attosecond time
      resolution and tunnelling delay times. Here we study laser-induced tunnelling by
      using a weak probe field to steer the tunnelled electron in the lateral direction
      and then monitor the effect on the attosecond light bursts emitted when the
      liberated electron re-encounters the parent ion. We show that this approach
      allows us to measure the time at which the electron exits from the tunnelling
      barrier. We demonstrate the high sensitivity of the measurement by detecting
      subtle delays in ionization times from two orbitals of a carbon dioxide molecule.
      Measurement of the tunnelling process is essential for all attosecond experiments
      where strong-field ionization initiates ultrafast dynamics. Our approach provides
      a general tool for time-resolving multi-electron rearrangements in atoms and
      molecules--one of the key challenges in ultrafast science.

PMID- 22596158
TI  - Light-induced liquid crystallinity.
AB  - Liquid crystals are traditionally classified as thermotropic, lyotropic or
      polymeric, based on the stimulus that governs the organization and order of the
      molecular system. The most widely known and applied class of liquid crystals are
      a subset of thermotropic liquid crystals known as calamitic, in which adding heat
      can result in phase transitions from or into the nematic, cholesteric and smectic
      mesophases. Photoresponsive liquid-crystal materials and mixtures can undergo
      isothermal phase transitions if light affects the order parameter of the system
      within a mesophase sufficiently. In nearly all previous examinations, light
      exposure of photoresponsive liquid-crystal materials and mixtures resulted in
      order-decreasing photo-induced isothermal phase transitions. Under specialized
      conditions, an increase in order with light exposure has been reported, despite
      the tendency of the photoresponsive liquid-crystal system to reduce order in the
      exposed state. A direct, photo-induced transition from the isotropic to the
      nematic phase has been observed in a mixture of spiropyran molecules and a
      nematic liquid crystal. Here we report a class of naphthopyran-based materials
      that exhibit photo-induced conformational changes in molecular structure capable
      of yielding order-increasing phase transitions. Appropriate functionalization of
      the naphthopyran molecules leads to an exceedingly large order parameter in the
      open form, which results in a clear to strongly absorbing dichroic state. The
      increase in order with light exposure has profound implications in optics,
      photonics, lasing and displays and will merit further consideration for
      applications in solar energy harvesting. The large, photo-induced dichroism
      exhibited by the material system has been long sought in ophthalmic applications
      such as photochromic and polarized variable transmission sunglasses.

PMID- 22596159
TI  - Recent Northern Hemisphere tropical expansion primarily driven by black carbon
      and tropospheric ozone.
AB  - Observational analyses have shown the width of the tropical belt increasing in
      recent decades as the world has warmed. This expansion is important because it is
      associated with shifts in large-scale atmospheric circulation and major climate
      zones. Although recent studies have attributed tropical expansion in the Southern
      Hemisphere to ozone depletion, the drivers of Northern Hemisphere expansion are
      not well known and the expansion has not so far been reproduced by climate
      models. Here we use a climate model with detailed aerosol physics to show that
      increases in heterogeneous warming agents--including black carbon aerosols and
      tropospheric ozone--are noticeably better than greenhouse gases at driving
      expansion, and can account for the observed summertime maximum in tropical
      expansion. Mechanistically, atmospheric heating from black carbon and
      tropospheric ozone has occurred at the mid-latitudes, generating a poleward shift
      of the tropospheric jet, thereby relocating the main division between tropical
      and temperate air masses. Although we still underestimate tropical expansion, the
      true aerosol forcing is poorly known and could also be underestimated. Thus,
      although the insensitivity of models needs further investigation, black carbon
      and tropospheric ozone, both of which are strongly influenced by human
      activities, are the most likely causes of observed Northern Hemisphere tropical
      expansion.

PMID- 22596160
TI  - KCTD13 is a major driver of mirrored neuroanatomical phenotypes of the 16p11.2
      copy number variant.
AB  - Copy number variants (CNVs) are major contributors to genetic disorders. We have
      dissected a region of the 16p11.2 chromosome--which encompasses 29 genes--that
      confers susceptibility to neurocognitive defects when deleted or duplicated.
      Overexpression of each human transcript in zebrafish embryos identified KCTD13 as
      the sole message capable of inducing the microcephaly phenotype associated with
      the 16p11.2 duplication, whereas suppression of the same locus yielded the
      macrocephalic phenotype associated with the 16p11.2 deletion, capturing the
      mirror phenotypes of humans. Analyses of zebrafish and mouse embryos suggest that
      microcephaly is caused by decreased proliferation of neuronal progenitors with
      concomitant increase in apoptosis in the developing brain, whereas macrocephaly
      arises by increased proliferation and no changes in apoptosis. A role for KCTD13
      dosage changes is consistent with autism in both a recently reported family with
      a reduced 16p11.2 deletion and a subject reported here with a complex 16p11.2
      rearrangement involving de novo structural alteration of KCTD13. Our data suggest
      that KCTD13 is a major driver for the neurodevelopmental phenotypes associated
      with the 16p11.2 CNV, reinforce the idea that one or a small number of
      transcripts within a CNV can underpin clinical phenotypes, and offer an efficient
      route to identifying dosage-sensitive loci.

PMID- 22596161
TI  - Reach and grasp by people with tetraplegia using a neurally controlled robotic
      arm.
AB  - Paralysis following spinal cord injury, brainstem stroke, amyotrophic lateral
      sclerosis and other disorders can disconnect the brain from the body, eliminating
      the ability to perform volitional movements. A neural interface system could
      restore mobility and independence for people with paralysis by translating
      neuronal activity directly into control signals for assistive devices. We have
      previously shown that people with long-standing tetraplegia can use a neural
      interface system to move and click a computer cursor and to control physical
      devices. Able-bodied monkeys have used a neural interface system to control a
      robotic arm, but it is unknown whether people with profound upper extremity
      paralysis or limb loss could use cortical neuronal ensemble signals to direct
      useful arm actions. Here we demonstrate the ability of two people with long
      standing tetraplegia to use neural interface system-based control of a robotic
      arm to perform three-dimensional reach and grasp movements. Participants
      controlled the arm and hand over a broad space without explicit training, using
      signals decoded from a small, local population of motor cortex (MI) neurons
      recorded from a 96-channel microelectrode array. One of the study participants,
      implanted with the sensor 5 years earlier, also used a robotic arm to drink
      coffee from a bottle. Although robotic reach and grasp actions were not as fast
      or accurate as those of an able-bodied person, our results demonstrate the
      feasibility for people with tetraplegia, years after injury to the central
      nervous system, to recreate useful multidimensional control of complex devices
      directly from a small sample of neural signals.

PMID- 22596162
TI  - RNF12 initiates X-chromosome inactivation by targeting REX1 for degradation.
AB  - Evolution of the mammalian sex chromosomes has resulted in a heterologous X and Y
      pair, where the Y chromosome has lost most of its genes. Hence, there is a need
      for X-linked gene dosage compensation between XY males and XX females. In
      placental mammals, this is achieved by random inactivation of one X chromosome in
      all female somatic cells. Upregulation of Xist transcription on the future
      inactive X chromosome acts against Tsix antisense transcription, and spreading of
      Xist RNA in cis triggers epigenetic changes leading to X-chromosome inactivation.
      Previously, we have shown that the X-encoded E3 ubiquitin ligase RNF12 is
      upregulated in differentiating mouse embryonic stem cells and activates Xist
      transcription and X-chromosome inactivation. Here we identify the pluripotency
      factor REX1 as a key target of RNF12 in the mechanism of X-chromosome
      inactivation. RNF12 causes ubiquitination and proteasomal degradation of REX1,
      and Rnf12 knockout embryonic stem cells show an increased level of REX1. Using
      chromatin immunoprecipitation sequencing, REX1 binding sites were detected in
      Xist and Tsix regulatory regions. Overexpression of REX1 in female embryonic stem
      cells was found to inhibit Xist transcription and X-chromosome inactivation,
      whereas male Rex1(+/-) embryonic stem cells showed ectopic X-chromosome
      inactivation. From this, we propose that RNF12 causes REX1 breakdown through dose
      dependent catalysis, thereby representing an important pathway to initiate X
      chromosome inactivation. Rex1 and Xist are present only in placental mammals,
      which points to co-evolution of these two genes and X-chromosome inactivation.

PMID- 22596163
TI  - Structure of the nociceptin/orphanin FQ receptor in complex with a peptide
      mimetic.
AB  - Members of the opioid receptor family of G-protein-coupled receptors (GPCRs) are
      found throughout the peripheral and central nervous system, where they have key
      roles in nociception and analgesia. Unlike the 'classical' opioid receptors,
      delta, kappa and MU (delta-OR, kappa-OR and MU-OR), which were delineated by
      pharmacological criteria in the 1970s and 1980s, the nociceptin/orphanin FQ
      (N/OFQ) peptide receptor (NOP, also known as ORL-1) was discovered relatively
      recently by molecular cloning and characterization of an orphan GPCR. Although it
      shares high sequence similarity with classical opioid GPCR subtypes (~60%), NOP
      has a markedly distinct pharmacology, featuring activation by the endogenous
      peptide N/OFQ, and unique selectivity for exogenous ligands. Here we report the
      crystal structure of human NOP, solved in complex with the peptide mimetic
      antagonist compound-24 (C-24) (ref. 4), revealing atomic details of ligand
      receptor recognition and selectivity. Compound-24 mimics the first four amino
      terminal residues of the NOP-selective peptide antagonist UFP-101, a close
      derivative of N/OFQ, and provides important clues to the binding of these
      peptides. The X-ray structure also shows substantial conformational differences
      in the pocket regions between NOP and the classical opioid receptors kappa (ref.
      5) and MU (ref. 6), and these are probably due to a small number of residues that
      vary between these receptors. The NOP-compound-24 structure explains the
      divergent selectivity profile of NOP and provides a new structural template for
      the design of NOP ligands.

PMID- 22596164
TI  - Structure of the delta-opioid receptor bound to naltrindole.
AB  - The opioid receptor family comprises three members, the u-, delta- and kappa
      opioid receptors, which respond to classical opioid alkaloids such as morphine
      and heroin as well as to endogenous peptide ligands like endorphins. They belong
      to the G-protein-coupled receptor (GPCR) superfamily, and are excellent
      therapeutic targets for pain control. The delta-opioid receptor (delta-OR) has a
      role in analgesia, as well as in other neurological functions that remain poorly
      understood. The structures of the u-OR and kappa-OR have recently been solved.
      Here we report the crystal structure of the mouse delta-OR, bound to the subtype
      selective antagonist naltrindole. Together with the structures of the u-OR and
      kappa-OR, the delta-OR structure provides insights into conserved elements of
      opioid ligand recognition while also revealing structural features associated
      with ligand-subtype selectivity. The binding pocket of opioid receptors can be
      divided into two distinct regions. Whereas the lower part of this pocket is
      highly conserved among opioid receptors, the upper part contains divergent
      residues that confer subtype selectivity. This provides a structural explanation
      and validation for the 'message-address' model of opioid receptor pharmacology,
      in which distinct 'message' (efficacy) and 'address' (selectivity) determinants
      are contained within a single ligand. Comparison of the address region of the
      delta-OR with other GPCRs reveals that this structural organization may be a more
      general phenomenon, extending to other GPCR families as well.

PMID- 22596166
TI  - Performance of a multi-biomarker score measuring rheumatoid arthritis disease
      activity in the CAMERA tight control study.
AB  - OBJECTIVES: To evaluate the performance of individual biomarkers and a multi
      biomarker disease activity (MBDA) score in the early rheumatoid arthritis (RA)
      patient population from the computer assisted management in early rheumatoid
      arthritis (CAMERA) study. METHODS: Twenty biomarkers were measured in the CAMERA
      cohort, in which patients were treated with either intensive or conventional
      methotrexate-based treatment strategies. The MBDA score was calculated using the
      concentrations of 12 biomarkers (SAA, IL-6, TNF-RI, VEGF-A, MMP-1, YKL-40, MMP-3,
      EGF, VCAM-1, leptin, resistin and CRP) according to a previously trained
      algorithm. The performance of the scores was evaluated relative to clinical
      disease activity assessments. Change in MBDA score over time was assessed by
      paired Wilcoxon rank sum test. Logistic regression was used to evaluate the
      ability of disease activity measures to predict radiographic progression.
      RESULTS: The MBDA score had a significant correlation with the disease activity
      score based on 28 joints-C reactive protein (DAS28-CRP) (r=0.72; p<0.001) and an
      area under the receiver operating characteristic curve for distinguishing
      remission/low from moderate/high disease activity of 0.86 (p<0.001) using a DAS28
      CRP cut-off of 2.7. In multivariate analysis the MBDA score, but not CRP, was an
      independent predictor of disease activity measures. Additionally, mean (SD) MBDA
      score decreased from 53 (18) at baseline to 39 (16) at 6 months in response to
      study therapy (p<0.0001). Neither MBDA score nor clinical variables were
      predictive of radiographic progression. CONCLUSIONS: This multi-biomarker test
      performed well in the assessment of disease activity in RA patients in the CAMERA
      study. Upon further validation, this test could be used to complement currently
      available disease activity measures and improve patient care and outcomes.

PMID- 22596167
TI  - JAK2 V617F down-modulates MPL.
AB  - Decreased expression of the thrombopoietin receptor (TPOR or MPL) on the cell
      surface of platelets and megakaryocytes is an established feature of and
      myelofibrosis; however, the exact mechanism responsible for this phenomenon has
      gone largely unexplained. In this issue of Blood, Pecquet and colleagues publish
      an excellent study revealing that MPL expression is downregulated in the context
      of the mutant protein, JAK2V617F.

PMID- 22596168
TI  - Hitting the target in MCL.
AB  - One of the major challenges in the evaluation of new therapies for lymphoma and
      other hematologic malignancies has been the ability to demonstrate changes in
      important biomarkers and pharmacodynamic end points in the tumor cell
      population.In this issue of Blood, Leonard et al provide an elegant evaluation of
      the cyclin-dependent kinase (cdk) inhibitor PD0332991 in patients with relapsed
      mantle cell lymphoma. Their results suggest that the combination of functional
      imaging using fluorothymidine-positron emission tomography (FLT-PET) and
      immunohistochemistry can provide important information about target inhibition in
      tumor cells, and the effects this inhibition has on proliferation and metabolism.

PMID- 22596169
TI  - Chopped and diced: Dicer1 deletion generates myeloid dysplasia.
AB  - Gene targeting studies revealed that Dicer1 is required for murine
      embryogenesis.In this issue of Blood, Alemdehy and colleagues examine deletion of
      Dicer1 in myeloid progenitor cells using a conditional Cebpa-Cre allele. They
      show that deletion of Dicer1 is required for viability and that Dicer1 regulates
      steps of neutrophil maturation.

PMID- 22596170
TI  - NHERF-2 silences the silencers.
AB  - Hyperresponsiveness to growth factors underlies a wide variety of human
      diseases,including hemangiomas, the most common tumor of childhood. Hemangiomas
      have been found to be clonal neoplasms of endothelial cells, with somatic
      mutations in unknown genes likely to be responsible for their development.

PMID- 22596171
TI  - Human Langerhans cells are immature in melanoma sentinel lymph nodes.

PMID- 22596172
TI  - Generation of Th17 from human naive CD4+ T cells preferentially occurs from
      FOXP3+ Tregs upon costimulation via CD28 or CD5.

PMID- 22596173
TI  - Genomic loss of patient-specific HLA in acute myeloid leukemia relapse after well
      matched unrelated donor HSCT.

PMID- 22596174
TI  - Association of adiposity trajectories with insulin sensitivity and glycemic
      deterioration: a longitudinal study of rural Chinese twin adults.
AB  - OBJECTIVE: To evaluate associations between adiposity trajectories over time and
      insulin sensitivity and glucose deterioration in a Chinese twin cohort. RESEARCH
      DESIGN AND METHODS: This study focused on 341 males and 292 females aged 20-50
      years at baseline who had physical clinical examinations and oral glucose
      tolerance test at two time points with an average of 6 years apart. BMI, waist
      circumference, percent body fat (PBF), and percent trunk fat (PTF) trajectories
      were classified into five track groups based on age- and sex-specific tertiles at
      each visit. We calculated the odds of the insulin sensitivity index((0,120))
      [ISI((0,120))] or glycemic deterioration at follow-up among five defined
      trajectories (tertile(baseline) -> tertile(follow-up)) using generalized estimate
      equation models. Additionally, we applied structural equation models to examine
      genetic and environmental influences on adiposity, adiposity change over time
      (ACO), ISI((0,120)), and the interrelationships among them. RESULTS: Participants
      with stable adiposity (BMI, waist circumference, PBF, and PTF) in the highest
      tertile or shifting to the highest tertile tended to have the lowest ISI((0,120))
      at follow-up or experience glycemic deterioration. Genetic factors exerted the
      major influence on adiposity, but environmental factors unique to each twin
      contributed more strongly to ISI and ACO. Correlations between adiposity/ACO and
      insulin sensitivity were mainly due to environmental influences. CONCLUSIONS:
      When adiposity stays or becomes high, insulin sensitivity falls and risk of
      glycemic deterioration rises. Additionally, we found that genetic factors exerted
      the major influence on adiposity, while environmental factors played the
      principal role for ACO and insulin sensitivity.

PMID- 22596175
TI  - Racial differences in association of elevated interleukin-18 levels with type 2
      diabetes: the Atherosclerosis Risk in Communities study.
AB  - OBJECTIVE: Elevated plasma interleukin-18 (IL-18) has been linked to onset of
      diabetes mellitus (DM) and its complications. However, so far this association
      has been shown only in predominantly white populations. We examined IL-18 levels
      and their association with incident DM in a racially heterogeneous population.
      RESEARCH DESIGN AND METHODS: In a nested case-cohort design representing a 9-year
      follow-up of 9,740 middle-aged, initially healthy, nondiabetic white and African
      American participants of the Atherosclerosis Risk in Communities Study, we
      selected and measured analytes on race-stratified (50% white, 50% African
      American) random samples of both cases of incident diabetes (n = 548) and
      eligible members of the full cohort (n = 536). RESULTS Baseline IL-18 levels were
      significantly higher in white participants compared with African American
      participants (P < 0.001). Although white participants in the fourth (versus
      first) quartile of IL-18 levels had a significant hazard ratio (HR) for
      developing DM (HR: 2.1, 95% CI: 1.3-3.4), after adjustment for age, sex, and
      study center, no difference was seen among African Americans (HR: 1.0, 95% CI:
      0.6-1.7). Unlike those in African Americans, IL-18 levels in whites had a
      significant correlation with age (P < 0.01); anthropometric characteristics such
      as waist circumference (P < 0.001), height (P = 0.04), waist-to-hip ratio (P <
      0.001), and BMI (P < 0.01); and total (P < 0.001) and high-molecular-weight (P <
      0.001) adiponectin. CONCLUSIONS: There are racial differences in levels of IL-18
      and the association of IL-18 with risk factors and incident type 2 DM. In
      addition, there seems to be a complex interplay of inflammation and adiposity in
      the development of DM.

PMID- 22596176
TI  - Role of muscle mass and muscle quality in the association between diabetes and
      gait speed.
AB  - OBJECTIVE: Older people with type 2 diabetes are at high risk of mobility
      disability. We investigated the association of diabetes with lower-limb muscle
      mass and muscle quality to verify whether diabetes-related muscle impairments
      mediate the association between diabetes and low walking speed. RESEARCH DESIGN
      AND METHODS: We performed a cross-sectional analysis of 835 participants (65
      years old and older) enrolled in the InCHIANTI (Invecchiare in Chianti, aging in
      the Chianti area) population-based study. Total, muscular, and fat cross
      sectional areas of the calf and relative muscle density were measured using
      peripheral quantitative computerized tomography. Indicators of muscle performance
      included knee-extension torque, ankle plantar flexion and dorsiflexion strength,
      lower-extremity muscle power, and ankle muscle quality (ratio of ankle strength
      to the muscle area [kilograms per centimeters squared]). Gait performance was
      assessed by 4- and 400-m walking speed. Diabetes was ascertained by standard
      American Diabetes Association criteria. RESULTS: Prevalence of diabetes was
      11.4%. After adjustment for age and sex, participants with diabetes had lower
      muscle density, knee and ankle strength, and muscle power and worse muscle
      quality (all P < 0.05). Diabetic participants were also slower on both 4-m (beta:
      -0.115 +/- 0.024 m/s, P < 0.001) and 400-m (beta:-0.053 +/- 0.023 m/s, P < 0.05)
      walking tests. In multivariable linear regression models, lower-limb muscle
      characteristics accounted for 24.3 and 15.1% of walking speed difference
      comparing diabetic and nondiabetic subjects in the 4- and 400-m walks,
      respectively. CONCLUSIONS: In older persons, diabetes is associated with reduced
      muscle strength and worse muscle quality. These impairments are important
      contributors of walking limitations related to diabetes.

PMID- 22596178
TI  - Vibrational circular dichroism versus optical rotation dispersion and electronic
      circular dichroism for diastereomers: the stereochemistry of 3-(1'-hydroxyethyl)
      1-(3'-phenylpropanoyl)-azetidin-2-one.
AB  - The absolute configuration of a relatively large and conformationally flexible
      chiral compound, 3-(1'-hydroxyethyl)-1-(3'-phenylpropanoyl)-azetidin-2-one, is
      determined using Vibrational Circular Dichroism (VCD) spectroscopy, Optical
      Rotation Dispersion (ORD) and Electronic Circular Dichroism (ECD). To that end a
      state of the art experimental VCD spectrum is compared to a theoretical spectrum
      and the absolute configuration is assigned. ORD and ECD are also used in the
      assignment to investigate the complementarity of the three techniques. VCD
      spectroscopy is found to have important advantages over ORD and ECD for
      diastereomers. The concept of robust modes is applied to this conformationally
      flexible molecule, showing that its use is limited for such large and flexible
      molecules. 

PMID- 22596177
TI  - Meat consumption and its association with C-reactive protein and incident type 2
      diabetes: the Rotterdam Study.
AB  - OBJECTIVE: To investigate whether intake of different types of meat is associated
      with circulating C-reactive protein (CRP) and risk of type 2 diabetes in a
      prospective cohort study. RESEARCH DESIGN AND METHODS: Our analysis included
      4,366 Dutch participants who did not have diabetes at baseline. During a median
      follow-up period of 12.4 years, 456 diabetes cases were confirmed. Intake of red
      meat, processed meat, and poultry was derived from a food frequency
      questionnaire, and their association with serum high-sensitivity CRP was examined
      cross-sectionally using linear regression models. Their association with risk of
      type 2 diabetes was examined using multivariate Cox proportional hazards model,
      including age, sex, family history of diabetes, and lifestyle and dietary
      factors. RESULTS: An increment of 50 g of processed meat was associated with
      increased CRP concentration (beta(processed meat) = 0.12; P = 0.01), whereas
      intake of red meat and poultry was not. When comparing the highest to the lowest
      category of meat intake with respect to diabetes incidence, the adjusted relative
      risks were as follows: for red meat (1.42 [95% CI 1.06-1.91]), for processed meat
      (1.87 [1.26-2.78]), and for poultry (0.95 [0.74-1.22]). Additional analysis
      showed that the associations were not affected appreciably after inclusion of CRP
      into the model. After adjustment for BMI, however, the association for red meat
      attenuated to 1.18 (0.88-1.59). CONCLUSIONS: Intake of processed meat is
      associated with higher risk of type 2 diabetes. It appears unlikely that CRP
      mediates this association.

PMID- 22596179
TI  - Polyethyleneimine coating renders polycarbonate resistant to organic solvents.
AB  - We propose a method for the modification of surfaces of microchannels in chips
      fabricated in polycarbonate (PC) that makes the devices resistant to a range of
      organic solvents. Coating of PC with branched polyethyleneimine (BPEI) with the
      use of trimethylpropane triglycidyl ether (TTE) as a linker renders the devices
      resistant to toluene, benzene, acetonitrile, tetrahydrofuran, dioxane and
      ethylene dichloride. The optimized procedure of modification allows for
      continuous operation of the chips for several hours without dissolution of PC.
      Additional modification with the use of Krytox(r) allows for the use of
      Fluorinert (FC-40) as the continuous phase and for generation and handling of
      droplets of organic solvents that are miscible with water.

PMID- 22596180
TI  - Karyometric comparison of splenic and gastric marginal zone lymphomas.
AB  - BACKGROUND: Marginal zone lymphomas are indolent B-cell lymphomas associated with
      autoimmunity and chronic inflammation. The two most frequent variants are mucosa
      associated lymphoid tissues marginal zone lymphomas and splenic marginal zone
      lymphomas. The aim of the study was to determine if it is possible to classify
      splenic and gastric lymphomas according to karyometric features. METHODS: The
      material consisted of 16 splenic and 14 gastric lymphomas. The measurements were
      done with the AnalySIS image analysis system. In each case at least 100 nuclei
      were selected, and 19 different geometric parameters were measured. RESULTS: On
      statistical analysis, the nuclei of splenic and gastric lymphomas showed
      differences in most parameters, but significant overlap of the values was
      present. Neural networks were trained and used for classification of the data. By
      this method, the nuclei were properly classified with a sensitivity of 0.75 and
      specificity of 0.71. In addition, in all the cases the majority of the nuclei
      were properly classified, thus allowing correct classification of all the cases
      into "splenic" or "gastric". CONCLUSION: These results support the view that
      mucosa-associated lymphoid tissue lymphomas and splenic marginal-zone lymphomas
      are separate entities.

PMID- 22596181
TI  - Predictive role of telomerase activity in the clinical outcome of patients with
      benign lesions of the uterine cervix or CIN.
AB  - Telomerase, a fundamental marker of neoplastic transformation, is widely
      expressed in both premalignant intraepithelial lesions and in most malignant
      lesions of the uterine cervix. We determined telomerase activity (TA) in uterine
      cervix by Repeat Amplification Protocol (TRAP) in a series of 62 cases, 44 with
      benign diseases (inflammation and/or metaplasia and/or acanthosis) and 18 with
      cervical intraepithelial neoplasia (CIN). No significant differences in TA were
      observed between benign lesions (median AEU value 36, range 0-119) and CIN
      (median AEU value 30, range 0-65). Conversely, TA was significantly higher in
      subjects who showed CIN evolution (65 range 45-119) than in disease-free
      individuals (34 range 0-95, rho = 0.017) and in 1 patient with a CIN2 lesion who
      relapsed after 5 years. Our results suggest that TA of the uterine cervix is
      capable of predicting CIN evolution or relapse, thus indicating its potential
      usefulness as a prognostic marker in clinical surveillance programs.

PMID- 22596182
TI  - Investigation and identification of let-7a related functional proteins in gastric
      carcinoma by proteomics.
AB  - MicroRNAs are small noncoding RNA molecules that control expression of target
      genes. Our previous studies show that let-7a decreased in gastric carcinoma and
      that up-regulation of let-7a by gene augmentation inhibited gastric carcinoma
      cell growth both in vitro and in vivo, whereas it remains largely unclear as to
      how let-7a affects tumor growth. In this study, proteins associated with the
      function of let-7a were detected by high throughout screening. The cell line of
      SGC-7901 stablely overexpressing let-7a was successfully established by gene
      cloning. Two-dimensional gel electrophoresis (2-DEy was used to separate the
      total proteins of SGC-7901/let-7a, SGC-7901/EV and SGC-7901, and PDQuest software
      was applied to analyze 2-DE images. Ten different protein spots were identified
      by MALDI-TOF-MS, and they may be the proteins associated with let-7a function.
      The overexpressed proteins included Antioxidant protein 2, Insulin-like growth
      factor binding protein 2, Protein disulfide isomerase A2, C-1-tetrahydrofolate
      synthase, Cyclin-dependent kinase inhibitor1 (CDKN1) and Rho-GTPase activating
      protein 4. The underexpressed proteins consisted of S-phase kinase-associated
      protein 2 (Spk2), Platelet membrane glycoprotein, Fibronectin and Cks1 protein.
      Furthermore, the different expression levels of the partial proteins (CDKN1, Spk2
      and Fibronectin) were confirmed by western blot analysis. The data suggest that
      these differential proteins are involved in a novel let-7a signal pathway and
      these findings provide the basis to investigate the functional mechanisms of let
      7a in gastric carcinoma.

PMID- 22596183
TI  - The prognostic value of adaptive nuclear texture features from patient gray level
      entropy matrices in early stage ovarian cancer.
AB  - BACKGROUND: Nuclear texture analysis gives information about the spatial
      arrangement of the pixel gray levels in a digitized microscopic nuclear image,
      providing texture features that may be used as quantitative tools for prognosis
      of human cancer. The aim of the study was to evaluate the prognostic value of
      adaptive nuclear texture features in early stage ovarian cancer. METHODS: 246
      cases of early stage ovarian cancer were included in the analysis. Isolated
      nuclei (monolayers) were prepared from 50 MUm tissue sections and stained with
      Feulgen-Schiff. Local gray level entropy was measured within small windows of
      each nuclear image and stored in gray level entropy matrices. A compact set of
      adaptive features was computed from these matrices. RESULTS: Univariate Kaplan
      Meier analysis showed significantly better relapse-free survival (p < 0.001) for
      patients with low adaptive feature values compared to patients with high adaptive
      feature values. The 10-year relapse-free survival was about 78% for patients with
      low feature values and about 52% for patients with high feature values. Adaptive
      features were found to be of independent prognostic significance for relapse-free
      survival in a multivariate analysis. CONCLUSION: Adaptive nuclear texture
      features from entropy matrices contain prognostic information and are of
      independent prognostic significance for relapse-free survival in early stage
      ovarian cancer.

PMID- 22596184
TI  - What is the prevalence of resistant hypertension in the United States?
AB  - PURPOSE OF REVIEW: Resistant hypertension, defined as blood pressure uncontrolled
      on three, or controlled with at least four, antihypertensive agents (including a
      diuretic), is associated with higher risk of secondary hypertension,
      cardiovascular and renal events, and increased healthcare expenditures. Until
      recently, however, the prevalence of resistant hypertension in the United States
      (US) was based on clinical trial registries or pharmacy databases. RECENT
      FINDINGS: Recent analyses of National Health and Nutrition Examination Survey
      (NHANES) data, drawn from representative samples of the adult,
      noninstitutionalized, civilian population, have estimated the prevalence of
      resistant hypertension at 8.9  +/-  0.6% of the US hypertensive population in
      2003-2008. A time-sequence comparison of NHANES data from 1998 through 2008
      suggests that, unlike hypertension, resistant hypertension is becoming more
      prevalent (e.g., 20.7% in 2005-2008), due to aging and increased obesity in the
      general population. Resistant hypertension was more frequent in people who were
      older, obese, male, African American or nonblack Hispanic. SUMMARY: In coming
      years, even if the prevalence of hypertension remains stable, resistant
      hypertension is likely to increase, especially as the proportion of treated
      hypertension increases. Because of increased use of healthcare resources,
      resistant hypertensive patients should be identified early, and greater efforts
      made to control their blood pressures.

PMID- 22596185
TI  - Contemporary pharmacological reperfusion in ST elevation myocardial infarction.
AB  - PURPOSE OF REVIEW: Fibrinolysis remains a key therapeutic alternative mode of
      reperfusion in patients with ST segment elevation myocardial infarction (STEMI).
      Its venerability relates to the wealth of clinical efficacy evidence, ease of
      administration, and broad applicability to the large number of patients who
      cannot receive mechanical reperfusion within a reasonable period of time. This
      review focuses on recent data that will further enhance the clinician's ability
      to deliver a pharmacological reperfusion strategy to this patient population.
      RECENT FINDINGS: Combined data from clinical trials as well as registry data
      support implementation of the guideline endorsed pharmacoinvasive strategy for
      patients unable to achieve rapid primary percutaneous coronary intervention. The
      most appropriate mode of reperfusion remains dependent upon the time from symptom
      onset to presentation as well as perceived delay to initiation of mechanical
      reperfusion therapy, and one strategy does not fit all patients at all times.
      Additional information is required in the growing population of elderly patients
      with STEMI to identify the most appropriate approach to reperfusion in this high
      risk population. SUMMARY: Despite extensive investigation concerning the optimal
      management of STEMI over the last three decades, significant knowledge gaps exist
      and the efficient application of current evidence to clinical practice remains
      elusive.

PMID- 22596186
TI  - Nonalcoholic fatty liver disease and vascular risk.
AB  - PURPOSE OF REVIEW: Nonalcoholic fatty liver disease (NAFLD) is an increasingly
      common condition, which is strongly associated with obesity and diabetes. The
      risk of cardiovascular disease is increased in NAFLD and represents the main
      cause of death in these patients. However, given the shared features between
      NAFLD, the metabolic syndrome and traditional cardiovascular risk factors,
      uncertainty exists as to whether NAFLD is an independent risk factor for
      increased cardiovascular disease. RECENT FINDINGS: Multiple epidemiological and
      case-control studies now demonstrate that NAFLD is associated with increased
      vascular risk, independently of conventional cardiometabolic risk factors.
      Evidence also suggests a graded association between NAFLD severity and increased
      vascular risk. However, given the heterogeneous disease spectrum of NAFLD, these
      findings have limitations with respect to accuracy of diagnosis and staging of
      NAFLD in most studies. SUMMARY: Although accumulating evidence points to NAFLD
      emerging as a novel cardiovascular risk factor, more research is needed to find
      suitable noninvasive biomarkers of NAFLD severity to allow better risk
      stratification based on cardiovascular outcomes. Furthermore, with no established
      pharmacological treatment option for NAFLD currently available, any potential
      treatment must show efficacy not only in slowing liver disease progression, but
      also in ameliorating adverse cardiovascular outcomes.

PMID- 22596188
TI  - FOXA1 is essential for aryl hydrocarbon receptor-dependent regulation of cyclin
      G2.
AB  - The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor
      that mediates the effects of the environmental contaminant 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD). Recently, AHR has emerged as a potential
      therapeutic target for breast cancer by virtue of its ability to modulate
      estrogen receptor-alpha (ERalpha) signalling and/or its ability to block cell
      proliferation. Our previous studies identified cyclin G2 (CCNG2), an inhibitor of
      cell-cycle progression, as an AHR target gene; however, the mechanism of this
      regulation is unknown. Chromatin immunoprecipitation assays in T-47D human breast
      cancer cells revealed a TCDD-dependent recruitment of AHR, nuclear co-activator 3
      (NCoA3) and the transcription factor forkhead box A1 (FOXA1), a key regulator of
      breast cancer cell signaling, to CCNG2 resulting in increases in CCNG2 mRNA and
      protein levels. Mutation of the AHR response element (AHRE) and forkhead-binding
      sites abolished TCDD-induced CCNG2-regulated reporter gene activity. RNA
      interference-mediated knockdown of FOXA1 prevented the TCDD-dependent recruitment
      of AHR and NCoA3 to CCNG2 and reduced CCNG2 mRNA levels. Interestingly, knockdown
      of FOXA1 also caused a marked decrease in ERalpha, but not AHR protein levels.
      However, RNA interference-mediated knockdown of ERalpha, a negative regulator of
      CCNG2, had no effect on TCDD-dependent AHR or NCoA3 recruitment to or expression
      of CCNG2. These findings show that FOXA1, but not ERalpha, is essential for AHR
      dependent regulation of CCNG2, assigning a role for FOXA1 in AHR action.

PMID- 22596189
TI  - Beyond blueprints.

PMID- 22596190
TI  - Teaching the design principles of metabolism.

PMID- 22596199
TI  - Structural biology: CrkL is not Crk-like.

PMID- 22596200
TI  - Biosynthesis: Ringing in a new view.

PMID- 22596201
TI  - Antisense therapeutics: New ways to nudge splicing.

PMID- 22596202
TI  - Rethinking glycolysis: on the biochemical logic of metabolic pathways.
AB  - Metabolic pathways may seem arbitrary and unnecessarily complex. In many cases, a
      chemist might devise a simpler route for the biochemical transformation, so why
      has nature chosen such complex solutions? In this review, we distill lessons from
      a century of metabolic research and introduce new observations suggesting that
      the intricate structure of metabolic pathways can be explained by a small set of
      biochemical principles. Using glycolysis as an example, we demonstrate how three
      key biochemical constraints--thermodynamic favorability, availability of
      enzymatic mechanisms and the physicochemical properties of pathway intermediates-
      eliminate otherwise plausible metabolic strategies. Considering these
      constraints, glycolysis contains no unnecessary steps and represents one of the
      very few pathway structures that meet cellular demands. The analysis presented
      here can be applied to metabolic engineering efforts for the rational design of
      pathways that produce a desired product while satisfying biochemical constraints.

PMID- 22596203
TI  - Engineering synthetic recursive pathways to generate non-natural small molecules.
AB  - Recursive pathways are broadly defined as those that catalyze a series of
      reactions such that the key, bond-forming functional group of the substrate is
      always regenerated in each cycle, allowing for a new cycle of reactions to begin.
      Recursive carbon-chain elongation pathways in nature produce fatty acids,
      polyketides, isoprenoids and alpha-keto acids (alphaKAs), which all use modular
      or iterative approaches for chain elongation. Recently, an artificial pathway for
      alphaKA elongation has been built that uses an engineered isopropylmalate
      synthase to recursively condense acetyl-CoA with alphaKAs. This synthetic
      approach expands the possibilities for recursive pathways beyond the modular or
      iterative synthesis of natural products and serves as a case study for
      understanding the challenges of building recursive pathways from nonrecursive
      enzymes. There exists the potential to design synthetic recursive pathways far
      beyond what nature has evolved.

PMID- 22596204
TI  - Natural strategies for the spatial optimization of metabolism in synthetic
      biology.
AB  - Metabolism is a highly interconnected web of chemical reactions that power life.
      Though the stoichiometry of metabolism is well understood, the multidimensional
      aspects of metabolic regulation in time and space remain difficult to define,
      model and engineer. Complex metabolic conversions can be performed by multiple
      species working cooperatively and exchanging metabolites via structured networks
      of organisms and resources. Within cells, metabolism is spatially regulated via
      sequestration in subcellular compartments and through the assembly of multienzyme
      complexes. Metabolic engineering and synthetic biology have had success in
      engineering metabolism in the first and second dimensions, designing linear
      metabolic pathways and channeling metabolic flux. More recently, engineering of
      the third dimension has improved output of engineered pathways through isolation
      and organization of multicell and multienzyme complexes. This review highlights
      natural and synthetic examples of three-dimensional metabolism both inter- and
      intracellularly, offering tools and perspectives for biological design.

PMID- 22596205
TI  - Systems metabolic engineering of microorganisms for natural and non-natural
      chemicals.
AB  - Growing concerns over limited fossil resources and associated environmental
      problems are motivating the development of sustainable processes for the
      production of chemicals, fuels and materials from renewable resources. Metabolic
      engineering is a key enabling technology for transforming microorganisms into
      efficient cell factories for these compounds. Systems metabolic engineering,
      which incorporates the concepts and techniques of systems biology, synthetic
      biology and evolutionary engineering at the systems level, offers a conceptual
      and technological framework to speed the creation of new metabolic enzymes and
      pathways or the modification of existing pathways for the optimal production of
      desired products. Here we discuss the general strategies of systems metabolic
      engineering and examples of its application and offer insights as to when and how
      each of the different strategies should be used. Finally, we highlight the
      limitations and challenges to be overcome for the systems metabolic engineering
      of microorganisms at more advanced levels.

PMID- 22596206
TI  - Does olanzapine inhibit the psychomimetic effects of Delta9-tetrahydrocannabinol?
AB  - Delta9-Tetrahydrocannabinol (THC) produces transient psychomimetic effects in
      healthy volunteers, constituting a pharmacological model for psychosis. The
      dopaminergic antagonist haloperidol has previously been shown to reduce these
      effects. This placebo-controlled, cross-over study in 49 healthy, male, mild
      cannabis users aimed to further explore this model by examining the effect of a
      single oral dose of olanzapine (with dopaminergic, serotonergic, adrenergic,
      muscarinergic and histaminergic properties) or two oral doses of diphenhydramine
      (histamine antagonist) on the effects of intrapulmonarily administered THC.
      Transient psychomimetic symptoms were seen after THC administration, as measured
      on the positive and negative syndrome scale (20.6% increase on positive subscale,
      p<0.001) and the visual analogue scale for psychedelic effects (increase of 10.7
      mm on feeling high). Following the combination of THC and olanzapine, the
      positive subscale increased by only 13.7% and feeling high by only 8.7 mm. This
      reduction of THC effects on the positive subscale failed to reach statistical
      significance (p=0.066). However, one-third of the subjects did not show an
      increase in psychomimetic symptoms after THC alone. Within responders, olanzapine
      reduced the effects of THC on the positive subscale (p=0.005). Other outcome
      measures included pharmacokinetics, eye movements, postural stability, pupil/iris
      ratio, and serum concentrations of cortisol and prolactin.

PMID- 22596207
TI  - The effect of phosphodiesterase inhibitors on the extinction of cocaine-induced
      conditioned place preference in mice.
AB  - Several phosphodiesterase inhibitors (PDEis) improve cognition, suggesting that
      an increase in brain cAMP and cGMP facilitates learning and memory. Since
      extinction of drug-seeking behavior requires associative learning, consolidation
      and formation of new memory, the present study investigated the efficacy of three
      different PDEis in the extinction of cocaine-induced conditioned place preference
      (CPP) in B6129S mice. Mice were conditioned by escalating doses of cocaine which
      was resistant to extinction by free exploration. Immediately following each
      extinction session mice received (a) saline/vehicle, (b) rolipram (PDE4
      inhibitor), (c) BAY-73-6691 (PDE9 inhibitor) or (d) papaverine (PDE10A
      inhibitor). Mice that received saline/vehicle during extinction training showed
      no reduction in CPP for >10 days. BAY-73-6691 (a) dose-dependently increased cGMP
      in hippocampus and amygdala, (b) significantly facilitated extinction and (c)
      diminished the reinstatement of cocaine CPP. Rolipram, which selectively
      increased brain cAMP levels, and papaverine which caused increases in both cAMP
      and cGMP levels, had no significant effect on the extinction of cocaine CPP. The
      results suggest that increase in hippocampal and amygdalar cGMP levels via
      blockade of PDE9 has a prominent role in the consolidation of extinction
      learning.

PMID- 22596208
TI  - Using an experimental medicine model to understand the antidepressant potential
      of the N-Methyl-D-aspartic acid (NMDA) receptor antagonist memantine.
AB  - There is growing interest in the role of the glutamatergic system both in
      depression and as a novel target for treatments. Preclinical studies suggested
      that the non-competitive N-Methyl-D-aspartic acid (NMDA) receptor antagonist
      memantine might have antidepressant properties, but a randomised controlled trial
      failed to support this. A healthy volunteer model of emotional processing was
      used to assess the neuropsychological profile of action of memantine. Healthy
      volunteers (n=32) were randomised to receive a single dose of memantine (10 mg)
      or placebo, and subsequently completed a battery of tasks measuring emotional
      processing, including facial expression recognition, emotional memory, dot-probe
      and emotion-potentiated startle tasks, as well as working and verbal memory.
      Memantine treated volunteers showed an increased emotion-potentiated startle, and
      a reduced bias for negative items in emotional recognition memory. There were no
      effects of the drug on any other aspect of emotional or non-emotional information
      processing. These results suggest that a single dose of memantine produces an
      early anxiogenic response in the emotion-potentiated startle similar to that seen
      following a single dose of the selective serotonin reuptake inhibitor,
      citalopram. However, the overall profile of effects is more limited than that
      which might be expected in response to a conventional antidepressant.

PMID- 22596209
TI  - Withdrawal and psychological sequelae, and patient satisfaction associated with
      subcutaneous flumazenil infusion for the management of benzodiazepine withdrawal:
      a case series.
AB  - Our group and others internationally have previously reported data on the use of
      low-dose flumazenil administered intravenously for the management of
      benzodiazepine withdrawal. This paper describes the first reported use of
      subcutaneous flumazenil infusion in the management of acute benzodiazepine
      withdrawal. Self-reported withdrawal symptoms and psychological state and anxiety
      sequelae were collected at baseline and then at intervals to 5 days following
      initiation of subcutaneous flumazenil infusion. Data indicate that patient
      subjective benzodiazepine withdrawal symptoms were well managed, with significant
      reduction in psychological distress seen over the duration of treatment.
      Perceived difficulty in performing everyday functions was positively correlated
      with withdrawal severity and improved over treatment. Patients reported high
      treatment comfort, willingness to undertake a future subsequent treatment using
      this technique, and willingness to recommend this treatment to a friend. This
      small proof-of-concept study indicates that subcutaneous flumazenil infusion has
      excellent tolerability, efficacy and improvement on measures of psychological
      distress. Given this technique is less invasive and requires fewer staff
      resources compared with intravenous administration, it may prove a significant
      asset in the management of benzodiazepine withdrawal.

PMID- 22596210
TI  - Interleukin-6 promotes destabilized angiogenesis by modulating angiopoietin
      expression in rheumatoid arthritis.
AB  - OBJECTIVE: To examine whether IL-6 promotes angiogenesis by modulating
      angiopoietin (Ang) expression in RA. METHODS: Synovial fibroblasts derived from
      RA patients (RASFs) and human umbilical vein endothelial cells (HUVECs) were co
      cultured for 6 days with or without recombinant IL-6, VEGF or Ang-1. HUVECs were
      stained with anti-CD31 antibody and their growth was determined by quantifying
      the CD31-positive area. SFs were collected from RA (n = 25) and OA (n = 7)
      patients. RESULTS: In the co-culture system, IL-6 and VEGF significantly enhanced
      HUVEC growth to a similar extent. However, the morphology of proliferating cells
      was distinct between IL-6- and VEGF-stimulated HUVEC. HUVEC stimulated with IL-6
      exhibited small, loose clusters surrounded by dispersed single cells, suggesting
      destabilized angiogenesis by IL-6. In the supernatants, IL-6 up-regulated VEGF
      compared with controls and Ang-2, while it down-regulated Ang-1. In contrast,
      down-regulation of Ang-1 was not observed with VEGF stimulation. Consistent with
      the destabilized morphology, stimulation with IL-6 decreased cell surface
      expression of vascular endothelial cadherin (VE-cadherin) on HUVEC, presumably by
      inducing internalization. Interestingly, adding recombinant Ang-1 partially
      inhibited IL-6-induced morphological changes in HUVEC including a destabilized
      morphology with small, loose clusters and internalization of VE-cadherin. In SFs
      from RA patients, VEGF was negatively correlated with Ang-1 (r = -0.559,
      P=0.004). CONCLUSION: IL-6 not only enhances VEGF expression but also inhibits
      Ang-1 signalling by directly down-regulating Ang-1 expression and up-regulating
      Ang-2, an antagonist of Ang-1. These synergistic effects may play a critical role
      in destabilized angiogenesis in RA.

PMID- 22596212
TI  - Jaccoud's arthropathy of the feet presenting as bilateral non-healing
      interdigital ulcers.

PMID- 22596211
TI  - Sustained efficacy of certolizumab pegol added to methotrexate in the treatment
      of rheumatoid arthritis: 2-year results from the RAPID 1 trial.
AB  - OBJECTIVE: To evaluate the safety and efficacy of 2-year administration of
      certolizumab pegol (CZP) + MTX in patients with active RA. METHODS: Patients
      completing 52 weeks in the Rheumatoid Arthritis Prevention of Structural Damage
      (RAPID) 1 trial (52-week completers), or withdrawing at week 16 due to lack of
      ACR20 response were eligible for open-label treatment (CZP 400 mg every other
      week + MTX). After 2 years' treatment, HAQ-Disability Index response, ACR20/50/70
      responses, DAS-28 and radiographic progression were assessed in 52-week
      completers. ACR20/50/70 and DAS-28 were also calculated for the intent-to-treat
      (ITT) population. Adverse events were assessed in patients who received one or
      more CZP doses during the study. RESULTS: At week 100, 88.9% (n = 216) of 52-week
      completers who originally received CZP 200 mg + MTX and open-label treatment
      remained in the study. In this group, ACR20/50/70 at week 100 were 68.2, 55.2 and
      35.6%, respectively. HAQ-DI and DAS-28 improvements were sustained throughout the
      open-label extension (mean change -0.79 and -3.5 at week 100, respectively). A
      total of 46.7% (n = 113) of CZP 200 mg + MTX 52-week completers achieved low
      disease activity by week 100. Inhibition of radiographic progression was
      maintained. Similar findings were observed in 52-week completers who originally
      received CZP 400 mg + MTX and in the ITT population. Rates of serious infection
      or malignancies did not increase over time and no new safety signals were
      observed. CONCLUSION: CZP + MTX provided sustained, 2-year inhibition of
      radiographic progression and sustained improvements in RA clinical signs and
      symptoms, with no new safety signals observed in patients who completed 2 years
      of treatment. TRIAL REGISTRATION: clinicaltrials.gov,
      http://www.clinicaltrials.gov, NCT00175877.

PMID- 22596213
TI  - Baseline vWF factor predicts the development of elevated pulmonary artery
      pressure in systemic sclerosis.
AB  - OBJECTIVES: This study aims to examine the utility of von Willebrand factor (vWF)
      as a biomarker in lcSSc, in particular the ability of vWF to predict the future
      development of disease manifestations in this disease. METHODS: vWFAg
      concentrations were measured in the serum of patients with lcSSc at baseline and
      at 3 years, during the QUINs trial [Prevention of Vascular Damage in Scleroderma
      with Angiotensin-Converting Enzyme (ACE) Inhibition]. %DL(CO), %KCO, %FVC,
      pulmonary artery pressure (PAP) estimation by echocardiography, Raynaud's attack
      frequency, Raynaud's severity, digital ulcer frequency, urinary protein
      excretion, estimated glomerular filtration rate (eGFR), modified Rodnan skin
      score and Medsger disease activity score were also measured at baseline and 3
      years. RESULTS: Baseline serum vWF concentrations were related to concurrent
      Medsger disease activity score, %DL(CO), %FVC, urinary protein excretion, eGFR
      and PAP >30 mmHg. In logistic regression models, baseline serum vWF
      concentrations were able to predict the future development of elevated PAP by
      echocardiography (PAP >40 mmHg, P = 0.001). CONCLUSIONS: Pulmonary artery
      hypertension is a life-threatening complication of lcSSc. vWF is a marker of
      endothelial cell activation. Raised serum concentrations of vWF in lcSSc increase
      the risk of developing subsequent elevation in PAP. Therefore screening patients
      with lcSSc for vWF may identify a group at risk of developing PAH. These patients
      could potentially be targeted with agents that stabilize the endothelium, e.g.
      statins.

PMID- 22596214
TI  - Interleukin-1beta measurement in stimulated whole blood cultures is useful to
      predict response to anti-TNF therapies in rheumatoid arthritis.
AB  - OBJECTIVE: In RA, response to TNF blockers may be associated with a profile of
      cytokine production unique to each patient. This study sought to predict the
      response to biologic agents by examining pro-inflammatory cytokine synthesis in
      stimulated whole blood cultures (WBCs). METHODS: We measured the concentration of
      TNF-alpha, IL-1beta and IL-6 in supernatants of lipopolysaccharide (LPS)
      stimulated WBCs obtained from RA patients (n = 41) before anti-TNF therapy
      (infliximab, 13; etanercept, 26; and adalimumab, 2) and from healthy controls (n
      = 12). At 24 weeks after biologics, whole bloods were again drawn from 14 of 41
      patients. Response was defined by the European League Against Rheumatism response
      criteria after 24 weeks of therapy. RESULTS: Among 41 patients, 32 were
      responders (good 14/moderate 18), while 9 were non-responders. All cytokines
      measured were significantly lower in RA patients than in controls. In RA, IL
      1beta production was lower in non-responders than in responders [median
      (interquartile range): 3.5 (1.5-9.4) vs 10.0 (5.1-93.1) pg/ml, P = 0.048]. The
      area under the curve from a receiver operating characteristic curve analysis for
      the prediction of response using IL-1beta was 0.717 (95% CI 0.520, 0.914). The
      sensitivity and specificity of IL-1beta (cut-off value 4.84 pg/ml) was 78.1 and
      77.8%, respectively. All cytokines were significantly higher 6 months later
      compared with their respective baseline. CONCLUSION: IL-1beta measurement in LPS
      stimulated WBC is useful to predict responsiveness to anti-TNF agents. Cytokine
      production capacities in LPS-stimulated WBCs are up-regulated by biologics.

PMID- 22596215
TI  - Physical activity, a lasting legacy from the 2012 Olympics and Paralympics.

PMID- 22596216
TI  - Virtual endoscopic imaging of the spine.
AB  - STUDY DESIGN: Prospective trial of virtual endoscopy in spinal surgery.
      OBJECTIVE: To investigate the utility of virtual endoscopy of the spine in
      conjunction with spinal surgery. SUMMARY OF BACKGROUND DATA: Several studies have
      described clinical applications of virtual endoscopy to visualize the inside of
      the bronchi, paranasal sinus, stomach, small intestine, pancreatic duct, and bile
      duct, but, to date, no study has described the use of virtual endoscopy in the
      spine. METHODS: Virtual endoscopy is a realistic 3-dimensional intraluminal
      simulation of tubular structures that is generated by postprocessing of computed
      tomographic data sets. Five patients with spinal disease were selected: 2
      patients with degenerative disease, 2 patients with spinal deformity, and 1
      patient with spinal injury. RESULTS: Virtual endoscopy software allows an
      observer to explore the spinal canal with a mouse, using multislice computed
      tomographic data. Our study found that virtual endoscopy of the spine has
      advantages compared with standard imaging methods because surgeons can
      noninvasively explore the spinal canal in all directions. CONCLUSION: Virtual
      endoscopy of the spine may be useful to surgeons for diagnosis, preoperative
      planning, and postoperative assessment by obviating the need to mentally
      construct a 3-dimensional picture of the spinal canal from 2-dimensional computed
      tomographic scans.

PMID- 22596218
TI  - Amyloid-beta fibril disruption by C60-molecular guidance for rational drug
      design.
AB  - The WHO has listed Alzheimer's disease among the major neurological disorders
      with an estimated 35 million people affected worldwide. Amyloid-beta is mostly
      believed to be the causative factor in Alzheimer's disease and the severity of
      the disease correlates with the tendency of amyloid-beta to form aggregation
      patterns-plaques. Lacking effective medication, the identification of any
      underlying mechanistic principles regarding plaque formation appears to be
      crucial. Here we carry out computer simulations to study the effect of C60 on
      structure and stability of an idealised pentameric construct of amyloid-beta
      units (a model fibril). A binding site on top of the structurally ordered stack
      of beta-sheets is identified that triggers structural alterations at the turn
      region of the hook-like beta-sheet assembly. Significant structural alterations
      are: (i) the destruction of regular helical twist, (ii) the loss of a stabilizing
      salt bridge and (iii) the loss of a stabilizing hydrophobic interaction close to
      the turn. Consequently, the main effect of C60 is the induction of sizable
      destabilization in native fibril structure. These structural insights may serve
      as a molecular guide for further rational drug design of effective inhibitors
      targeting fibril formation in Alzheimer's disease. 

PMID- 22596219
TI  - Ion diode logics for pH control.
AB  - Electronic control over the generation, transport, and delivery of ions is useful
      in order to regulate reactions, functions, and processes in various chemical and
      biological systems. Different kinds of ion diodes and transistors that exhibit
      non-linear current versus voltage characteristics have been explored to generate
      chemical gradients and signals. Bipolar membranes (BMs) exhibit both ion current
      rectification and water splitting and are thus suitable as ion diodes for the
      regulation of pH. To date, fast switching ion diodes have been difficult to
      realize due to accumulation of ions inside the device structure at forward bias-
      charges that take a long time to deplete at reverse bias. Water splitting occurs
      at elevated reverse voltage bias and is a feature that renders high ion current
      rectification impossible. This makes integration of ion diodes in circuits
      difficult. Here, we report three different designs of micro-fabricated ion
      bipolar membrane diodes (IBMDs). The first two designs consist of single BM
      configurations, and are capable of either splitting water or providing high
      current rectification. In the third design, water-splitting BMs and a highly
      rectifying BM are connected in series, thus suppressing accumulation of ions. The
      resulting IBMD shows less hysteresis, faster off-switching, and also a high ion
      current rectification ratio as compared to the single BM devices. Further, the
      IBMD was integrated in a diode-based AND gate, which is capable of controlling
      delivery of hydroxide ions into a receiving reservoir.

PMID- 22596220
TI  - Expression profiles of metabolic enzymes and drug transporters in the liver and
      along the intestine of beagle dogs.
AB  - Beagle dogs are widely used in preclinical pharmacokinetic, safety, and
      formulation studies. However, little is known about intestinal and hepatic
      distribution of major enzymes and transporters involved in oral absorption and
      presystemic drug metabolism. We characterized mRNA levels of CYP3A12, CYP3A26,
      CYP2D15, UGT1A6, ABCB1 (MDR1), ABCC1 (MRP1), ABCG2 (BCRP), SLC15A1 (PEPT1), and
      SLC22A1 (OCT1) in dog liver and along the intestine by real-time quantitative
      reverse transcription-polymerase chain reaction. Tissue protein levels of
      CYP2D15, MDR1, and PEPT1 were obtained by Western blot. Gene distribution and
      expression variability was statistically described by a generalized additive
      mixed model smoothing function and correspondence analysis. Results were compared
      with the expression pattern known for the human orthologs. Hepatic mRNA levels
      for metabolic enzymes were generally higher than those for membrane transporters,
      whereas in the intestine the opposite was observed. Hepatic mRNA levels followed
      the order CYP2D15 > UGT1A6 ~ CYP3A26 > ABCB1 ~ SLC15A1 ~ SLC22A1 > ABCG2 > ABCC1
      ~ CYP3A12. Along the gut, the genes were differentially distributed with greatest
      expression in duodenum/upper jejunum (ABCG2), middle jejunum (ABCB1 and SLC15A1),
      or in cecum/colon (ABCC1 and CYP2D15). CYP3A12, CYP3A26, SLC22A1, and UGT1A6 had
      a rather uniform expression. Intestinal mRNA profiles of CYP2D15, ABCB1, and
      SLC15A1 correlated with the respective protein levels. Canine CYP3A12/26,
      CYP2D15, and ABCB1 colonic distributions differed from those of human orthologs,
      whereas UGT1A6, ABCC1, ABCG2, SLC15A1, and SLC22A1 were comparable to those of
      humans in both small and large intestine. We aim to apply these data to better
      interpret pharmacokinetic studies in dogs with respect to their human relevance.

PMID- 22596222
TI  - Toll-like receptor 4 activation in microvascular endothelial cells triggers a
      robust inflammatory response and cross talk with mononuclear cells via
      interleukin-6.
AB  - OBJECTIVE: It is known that toll-like receptor 4 (TLR4) plays an important role
      in atherosclerosis. Because both microvascular (MIC) and macrovascular (MAC)
      endothelial cells (ECs) are present in atherosclerotic lesions, the present study
      compared TLR4-triggered inflammatory response and cross talk with mononuclear
      cells between MIC and MAC ECs. METHODS AND RESULTS: ELISA, real-time polymerase
      chain reaction, and gene expression profiling showed that TLR4 activation by
      lipopolysaccharide stimulated a much higher expression of inflammatory genes
      including cytokines, chemokines, growth factors, and adhesion molecules in MIC
      ECs than MAC ECs. Furthermore, coculture studies showed that TLR4 activation in
      MIC ECs, but not MAC ECs, induced a cross talk with U937 mononuclear cells
      through MIC EC-released interleukin-6 to upregulate matrix metalloproteinase-1
      expression in U937 cells. To explore molecular mechanisms underlying the
      different responses to TLR4 activation between MIC and MAC ECs, we showed that
      MIC ECs had a higher expression of TLR4 and CD14 and a higher TLR4-mediated
      nuclear factor-kappaB activity than MAC ECs. CONCLUSIONS: The present study
      showed that TLR4 activation triggers a more robust inflammatory response in MIC
      ECs than MAC ECs. Given the importance of inflammatory cytokines and matrix
      metalloproteinases in plaque rupture, MIC ECs may play a key role in plaque
      destabilization through a TLR4-dependent mechanism.

PMID- 22596223
TI  - In vitro analysis of the influence of surface treatment of dental implants on
      primary stability.
AB  - Surface treatment interferes with the primary stability of dental implants
      because it promotes a chemical and micromorphological change on the surface and
      thus stimulates osseointegration. This study aimed to evaluate the effects of
      different surface treatments on primary stability by analyzing insertion torque
      (IT) and pullout force (PF). Eight samples of implants with different surface
      treatments (TS - external hexagon with acid surface treatment; and MS - external
      hexagon, machined surface), all 3.75 mm in diameter X 11.5 mm in length, were
      inserted into segments of artificial bones. The IT of each sample was measured by
      an electronic torquemeter, and then the pullout test was done with a universal
      testing machine. The results were subjected to ANOVA (p < 0.05), followed by
      Tukey's test (p < 0.05). The IT results showed no statistically significant
      difference, since the sizes of the implants used were very similar, and the bone
      used was not highly resistant. The PF values (N) were, respectively, TS = 403.75
      +/- 189.80 and MS = 276.38 +/- 110.05. The implants were shown to be different in
      terms of the variables of maximum force (F = 4.401, p = 0.0120), elasticity in
      maximum flexion (F = 3.672, p = 0.024), and relative stiffness (F = 4.60, p =
      0.01). In this study, external hexagonal implants with acid surface treatment
      showed the highest values of pullout strength and better stability, which provide
      greater indication for their use.

PMID- 22596221
TI  - Mechanisms of cell death in heart disease.
AB  - The major cardiac syndromes, myocardial infarction and heart failure, are
      responsible for a large portion of deaths worldwide. Genetic and pharmacological
      manipulations indicate that cell death is an important component in the
      pathogenesis of both diseases. Cells die primarily by apoptosis or necrosis, and
      autophagy has been associated with cell death. Apoptosis has long been recognized
      as a highly regulated process. Recent data indicate that a significant subset of
      necrotic deaths is also programmed. In the review, we discuss the molecular
      mechanisms that underlie these forms of cell death and their interconnections.
      The possibility is raised that small molecules aimed at inhibiting cell death may
      provide novel therapies for these common and lethal heart syndromes.

PMID- 22596224
TI  - Mechanical fixation techniques for processing and orienting delicate samples,
      such as the root of Arabidopsis thaliana, for light or electron microscopy.
AB  - Despite improvements in live imaging, fixation followed by embedding and
      sectioning for light or electron microscopy remains an indispensible approach in
      biology. During processing, small or delicate samples can be lost, damaged or
      poorly oriented. Here we present a protocol for overcoming these issues when,
      along with chemical fixation, the sample is fixed mechanically. The protocol
      features two alternatives for mechanical fixation: the sample is encased either
      in a rectangular block of agarose or between Formvar films suspended on a wire
      loop. We also provide methods for key steps all the way through to sectioning. We
      illustrate the method on the root of Arabidopsis thaliana, an object that is
      ~0.15 mm in diameter and difficult to process conventionally. With this protocol,
      well-oriented sections can be obtained with excellent ultrastructural
      preservation. The protocol takes about 1 week.

PMID- 22596225
TI  - Mussel micronucleus cytome assay.
AB  - The micronucleus (MN) assay is one of the most widely used genotoxicity
      biomarkers in aquatic organisms, providing an efficient measure of chromosomal
      DNA damage occurring as a result of either chromosome breakage or chromosome mis
      segregation during mitosis. The MN assay is today applied in laboratory and field
      studies using hemocytes and gill cells from bivalves, mainly from the genera
      Mytilus. These represent 'sentinel' organisms because of their ability to survive
      under polluted conditions and to accumulate both organic and inorganic
      pollutants. Because the mussel MN assay also includes scoring of different cell
      types, including necrotic and apoptotic cells and other nuclear anomalies, it is
      in effect an MN cytome assay. The mussel MN cytome (MUMNcyt) assay protocol we
      describe here reports the recommended experimental design, sample size, cell
      preparation, cell fixation and staining methods. The protocol also includes
      criteria and photomicrographs for identifying different cell types and scoring
      criteria for micronuclei (MNi) and nuclear buds. The complete procedure requires
      approximately 10 h for each experimental point/sampling station (ten animals).

PMID- 22596227
TI  - Efficient introduction of specific TP53 mutations into mouse embryonic
      fibroblasts and embryonic stem cells.
AB  - This protocol describes a rapid, precise method for generating sets of embryonic
      stem (ES) cells or mouse embryonic fibroblasts (MEFs) harboring point mutations
      in the p53 tumor suppressor gene (officially known as Trp53). The strategy uses
      cells from the Trp53 (p53-null) 'platform' mouse, which allows site-specific
      integration of plasmid DNA into the Trp53 locus. Simple PCR protocols identify
      correctly targeted clones and immunoblots verify re-expression of the protein. We
      also present protocol modifications needed for efficient recovery of MEF clones
      expressing p53 constructs that retain wild-type function, including growth at low
      (3%) oxygen and transient downregulation of p53 regulators to forestall cell
      senescence of primary MEFs. A library of cell lines expressing various p53
      mutants derived from the same population of primary fibroblasts or platform ES
      cells can be acquired and screened in less than 1 month.

PMID- 22596226
TI  - Increased initiation and growth of tumor cell lines, cancer stem cells and biopsy
      material in mice using basement membrane matrix protein (Cultrex or Matrigel) co
      injection.
AB  - This protocol requires 2-4 h and presents a method for injecting tumor cells,
      cancer stem cells or dispersed biopsy material into subcutaneous or orthotopic
      locations within recipient mice. The tumor cells or biopsy are mixed with
      basement membrane matrix proteins (CultrexBME or Matrigel) at 4  degrees C and
      then injected into recipient animals at preferred anatomical sites. Tumor cells
      can also be co-injected with additional cell types, such as fibroblasts, stromal
      cells, endothelial cells and so on. Details are given on appropriate cell
      numbers, handling and concentration of the basement membrane proteins, recipient
      animals, injection location and techniques. This procedure enables the growth of
      tumors from cells or biopsy material (tumor graft) with greater efficiency of
      take and growth, and with retention of the primary tumor phenotype based on
      histology. Co-injection with additional cell types provides more physiological
      models of human cancers for use in drug screening and studying cancer biology.

PMID- 22596228
TI  - Natalizumab-associated reversible encephalopathy syndrome mimicking progressive
      multifocal leukoencephalopathy.
AB  - Progressive multifocal leukoencephalopathy is a rare but potentially lethal
      adverse event in natalizumab treated multiple sclerosis patients. We report on a
      40-year old Caucasian man with typical relapsing progressive multiple sclerosis,
      who developed a reversible leukoencephalopathy syndrome after 43 natalizumab
      infusions mimicking progressive multifocal leukoencephalopathy. To our knowledge,
      this is the first case of its kind. Our case suggests that awareness ought to be
      sharpened for reversible leukoencephalopathy syndrome in the follow-up of
      natalizumab treated multiple sclerosis patients.

PMID- 22596229
TI  - Microvascular responses to aldosterone in hamster cheek pouch microcirculation.
AB  - The aim of the present study was to assess the in vivo effects of aldosterone
      topically applied on the hamster cheek pouch microcirculation under baseline
      conditions or during ischemia-reperfusion. Male Syrian hamsters were
      anesthetized, tracheotomized and intubated. They were studied under baseline
      conditions or submitted to ischemia-reperfusion. Cheek pouch microvessels were
      visualized by fluorescence microscopy. Microvascular parameters were determined
      by computerized methods. Under baseline conditions, aldosterone (0.2, 0.5, 2.4
      MUM/L/2 min) induced dose-dependent constriction of all arterioles within 2.0 +/-
      0.5 min of administration. Diameter reduction was in the same range in smaller
      arterioles: A3 ones constricted by 24 +/- 3% of baseline (at the highest dose).
      Aldosterone applied prior to ischemia and at reperfusion caused arteriolar
      constriction, marked microvascular permeability (0.66 +/- 0.03 Normalized Grey
      Level), reduction in perfused capillary (-70 +/- 4% of baseline) and leukocyte
      adhesion. All changes were statistically significant compared with ischemic
      animals. Potassium canrenoate (mineralcorticoid receptor inhibitor) prior to
      aldosterone did not abolish the aldosterone-induced effects, while valsartan
      (angiotensin II AT1 receptor inhibitor) prior to aldosterone ameliorated
      microvascular ischemia-reperfusion injury. In conclusion, aldosterone determined
      dose-dependent arteriolar constriction likely by angiotensin II type-1 receptor
      activation (non-genomic mechanism) worsening the effects of ischemia-reperfusion
      on capillary perfusion, while protecting from free radical formation.

PMID- 22596230
TI  - Increased dense erythrocytes in flame-burned patients.
AB  - OBJECTIVE: We have studied dense erythrocytes separated on Arabinogalactan
      (Stractan) ultracentrifuged gradients in flame-burned patients and in normal
      individuals. In each case, the percentage of erythrocytes in the densest layers
      was increased when compared to age and sex matched controls. METHODS AND RESULTS:
      Using an in vitro system, we showed that as human whole blood is warmed to 48.6
      degrees C, the number of dense erythrocytes increases. In addition, the reduced
      glutathionine (GSH) content of the densest red blood cells is decreased compared
      to those in lighter fractions on the same gradient or to dense erythrocytes
      separated from blood incubated at room temperature. These dense red cells were
      largely composed of spherocytes and spheroechynocytes, two forms of erythrocytes
      which have been shown by others to have markedly abnormal flow characteristics in
      vitro. CONCLUSIONS: We have demonstrated that in vivo dense erythrocytes can be
      generated in the setting of flame burns. Thus, the underlying reason may be
      oxidant injury as represented by the reduced level of GSH that we found in
      association with the generation of dense erythrocytes.

PMID- 22596231
TI  - Influence of a radiographic contrast media (Iopentol) with different viscosities
      on capillary perfusion in patients with coronary artery disease.
AB  - Radiographic contrast media (RCM) are widely used to visualize blood vessels.
      Their effects on blood vessels should be minimal so that the object of the
      measurement - the vessel lumen - is not influenced by the RCM molecules. However,
      all RCMs exhibit a more or less strong effect on endothelial cells as well as on
      erythrocytes. These effects are discussed to induce a significant and relevant
      deceleration of the microcirculation. For some RCMs this could be demonstrated in
      animal or clinical studies. Therefore, this study investigated the role of the
      viscosity of a RCM on the mean erythrocyte velocity in nail fold capillaries in
      patients with coronary artery disease after a bolus injection of the RCM directly
      into the A. axillaris. Iopentol-350 is a high-viscous Xray contrast medium and
      induced a short-lasting imbalance of the microcirculation already in vascular
      regions not affected by atherosclerosis. This effect was - in the early phase
      after injection - significantly stronger than after application of the low
      viscous Iopentol-150. In patients with severe coronary artery disease and a
      myocardial perfusion at its limits, the injection of high-viscous X-ray contrast
      media could induce massive perturbations in the microcirculation and even
      ischemia. As a consequence a further impairment of both systolic and diastolic
      functions may occur.

PMID- 22596232
TI  - Activation of JNK and high expression level of CD133 predict a poor response to
      sorafenib in hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) ranks as the third leading cause of
      cancer deaths worldwide. While sorafenib, a multikinase inhibitor targeting the
      Raf/extracellular signal-regulated protein kinase (ERK) pathway, has been shown
      recently to provide a survival advantage to patients with advanced HCC, a
      predictive biomarker has not been developed. We studied whether c-Jun N-terminal
      kinase (JNK), which promotes liver carcinogenesis in mice, affects therapeutic
      response to sorafenib in HCC patients. METHODS: We collected pathological
      specimens from 39 patients with advanced HCC before starting sorafenib treatment,
      and measured JNK activity in HCCs. RESULTS: In patients treated with sorafenib,
      the expression of phospho-c-Jun in HCC, as a read out of JNK activity, was
      significantly higher (P<0.001) in the non-responder group than in the responder
      group. c-Jun N-terminal kinase activation in HCC was associated with a decreased
      time to progression and a poor overall survival (P=0.0028 and P=0.0008,
      respectively). CONCLUSION: In addition, JNK activity was significantly correlated
      with CD133 expression level. Correspondingly, high expression level of CD133 was
      linked to a poor response to sorafenib. Furthermore, D-JNKi, a specific JNK
      inhibitor, reduced the growth of xenografted CD133(+) cells in athymic mice. In
      conclusion, JNK activation was positively correlated with CD133 expression level
      and inversely correlated with the therapeutic response to sorafenib, suggesting
      that JNK activity may be considered as a new predictive biomarker for response to
      sorafenib treatment.

PMID- 22596233
TI  - Even-skipped homeobox 1 is frequently hypermethylated in prostate cancer and
      predicts PSA recurrence.
AB  - BACKGROUND: DNA methylation is an important epigenetic mechanism in prostate
      cancer (PCa) progression. Given the role of even-skipped homeobox 1 (EVX1) in the
      regulation of multiple genes during embryogenesis, we postulated that EVX1
      methylation is altered in PCa progression. METHODS: Bisulphite sequencing and
      quantitative MethyLight were used to assess methylation in human prostate
      epithelial cells, four PCa cell lines, liver, lung, spleen, kidney, 35 paired
      tumour and tumour-associated benign tissues, and 11 normal prostate tissues.
      Prostate cancer cell lines were treated with 5-azacytidine (AzaC) or trichostatin
      A (TSA), and expression of EVX1 transcript and variants was assessed by qPCR.
      Hypermethylation was compared with clinicopathological features in a validation
      set of 58 patients using microarray. RESULTS: Even-skipped homeobox 1
      hypermethylation was observed in all four PCa cell lines and 57% of tumours. High
      grade tumours exhibited increased methylation compared with intermediate-grade
      tumours. Even-skipped homeobox 1 expression was induced in PCa cell lines after
      treatment with AzaC or TSA. In the validation set, 83% of tumours were
      hypermethylated and hypermethylation was associated with worse recurrence-free
      survival. CONCLUSION: In this first evaluation of EVX1 methylation in human
      cancer, EVX1 is one of the most commonly hypermethylated genes observed in PCa
      and predicted treatment failure in moderate risk patients.

PMID- 22596234
TI  - gamma-Secretase inhibitor enhances antitumour effect of radiation in Notch
      expressing lung cancer.
AB  - BACKGROUND: Notch receptor has an important role in both development and cancer.
      We previously reported that inhibition of the Notch3 by gamma-secretase inhibitor
      (GSI) induces apoptosis and suppresses tumour proliferation in non-small-cell
      lung cancer. Although radiation is reported to induce Notch activation, little is
      known about the relationship between radiation and Notch pathway. METHODS: We
      examined the effect of combining GSI and radiation at different dosing in three
      Notch expressing lung cancer cell lines. The cytotoxic effect of GSI and
      radiation was evaluated using MTT assay and clonogenic assay in vitro and
      xenograft models. Expressions of Notch pathway, mitogen-activated protein kinase
      (MAPK) pathway and Bcl-2 family proteins were investigated using western blot
      analysis. RESULTS: We discovered that the antitumour effect of combining GSI and
      radiation was dependent on treatment schedule. gamma-Secretase inhibitor
      administration after radiation had the greatest growth inhibition of lung cancer
      in vitro and in vivo. We showed that the combination induced apoptosis of lung
      cancer cell lines through the regulation of MAPK and Bcl-2 family proteins.
      Furthermore, activation of Notch after radiation was ameliorated by GSI
      administration, suggesting that treatment with GSI prevents Notch-induced
      radiation resistance. CONCLUSION: Notch has an important role in lung cancer.
      Treatment with GSI after radiation can significantly enhance radiation-mediated
      tumour cytotoxicity.

PMID- 22596235
TI  - Value of DCE-MRI and FDG-PET/CT in the prediction of response to preoperative
      chemotherapy with bevacizumab for colorectal liver metastases.
AB  - BACKGROUND: The purpose of this study was to assess the role of dynamic contrast
      enhanced magnetic resonance imaging (DCE-MRI) and (18)F-fluorodeoxyglucose
      positron emission tomography computed tomography (FDG-PET/CT) for evaluation of
      response to chemotherapy and bevacizumab and for prediction of progression-free
      survival (PFS) in patients with metastatic colorectal cancer (mCRC) with
      potentially resectable liver lesions. METHODS: A total of 19 mCRC patients were
      treated with FOLFOX/FOLFIRI and bevacizumab followed by surgery. Dynamic contrast
      enhanced magnetic resonance imaging and FDG-PET/CT were performed before
      treatment and after cycle 5. PET results were quantified by calculating maximum
      standardised uptake value (SUV(max)) whereas area under the enhancement curve
      (AUC), initial AUC (iAUC) and the endothelial transfer constant (K(trans)) were
      used to quantify DCE-MRI. Pathological analysis of the resection specimen was
      performed, including measurement of microvessel density (MVD) and proliferation
      index. RESULTS: Both AUC and iAUC were significantly decreased following
      bevacizumab therapy (median change of 22% (P=0.002) and 40% (P=0.001) for AUC and
      iAUC, respectively). Progression-free survival benefit was shown for patients
      with >40% reduction in K(trans) (P=0.019). In the group of radiological
      responders, the median baseline SUV(max) was 3.77 (IQR: 2.88-5.60) compared with
      7.20 (IQR: 4.67-8.73) in nonresponders (P=0.021). A higher follow-up SUV(max) was
      correlated with worse PFS (P=0.012). Median MVD was 10.9. Progression-free
      survival was significantly shorter in patients with an MVD greater than 10,
      compared with patients with lower MVD (10 months compared with 16 months,
      P=0.016). CONCLUSION: High relative decrease in K(trans), low follow-up SUV(max)
      and low MVD are favourable prognostic factors for mCRC patients treated with
      bevacizumab before surgery.

PMID- 22596236
TI  - Small but significant socioeconomic inequalities in axillary staging and
      treatment of breast cancer in the Netherlands.
AB  - BACKGROUND: The use of sentinel node biopsy (SNB), lymph node dissection, breast
      conserving surgery, radiotherapy, chemotherapy and hormonal treatment for breast
      cancer was evaluated in relation to socioeconomic status (SES) in the
      Netherlands, where access to care was assumed to be equal. METHODS: Female breast
      cancer patients diagnosed between 1994 and 2008 were selected from the nationwide
      population-based Netherlands Cancer Registry (N=176 505). Socioeconomic status
      was assessed based on income, employment and education at postal code level.
      Multivariable models included age, year of diagnosis and stage. RESULTS: Sentinal
      node biopsy was less often applied in high-SES patients (multivariable analyses,
      <= 49 years: odds ratio (OR) 0.70 (95% CI: 0.56-0.89); 50-75 years: 0.85 (0.73
      0.99)). Additionally, lymph node dissection was less common in low-SES patients
      aged >= 76 years (OR 1.34 (0.95-1.89)). Socioeconomic status-related differences
      in treatment were only significant in the age group 50-75 years. High-SES women
      with stage T1-2 were more likely to undergo breast-conserving surgery
      (+radiotherapy) (OR 1.15 (1.09-1.22) and OR 1.16 (1.09-1.22), respectively).
      Chemotherapy use among node-positive patients was higher in the high-SES group,
      but was not significant in multivariable analysis. Hormonal therapy was not
      related to SES. CONCLUSION: Small but significant differences were observed in
      the use of SNB, lymph node dissection and breast-conserving surgery according to
      SES in Dutch breast cancer patients despite assumed equal access to health care.

PMID- 22596237
TI  - False-negative MRI biomarkers of tumour response to targeted cancer therapeutics.
AB  - BACKGROUND: Non-invasive quantitative imaging biomarkers are essential for the
      evaluation of novel targeted therapeutics. Before deployment in clinical trials,
      such imaging biomarkers require qualification, typically through pre-clinical
      identification of imaging-pathology correlates. METHODS: First, in investigating
      imaging biomarkers of invasion, the response of orthotopic murine PC3 prostate
      xenografts to the Src inhibitor saracatinib was assessed using susceptibility
      contrast MRI. Second, the longitudinal response of chemically induced rat mammary
      adenocarcinomas to the VEGFR2 inhibitor vandetanib was monitored by intrinsic
      susceptibility MRI, to identify the time window of transient vascular
      normalisation. RESULTS: No significant differences in fractional blood volume
      (%), vessel calibre (MUm), native T(1) (ms) or apparent water diffusion
      coefficient were determined, despite reduced expression of activated Fak and
      paxillin in the saracatinib cohort. Treatment with vandetanib elicited a 60%
      antitumour response (P<0.01), 80% inhibition in vessel density (P<0.05) and
      reduction in hypoxia (P<0.05). There was, however, no significant change in
      tumour baseline R(2)* (s(-1)) or carbogen-induced DeltaR(2)* with treatment.
      CONCLUSION: Reporting negative imaging biomarker responses is important, to avoid
      the risk of clinical trials using the same biomarkers being undertaken with a
      false expectation of success, and the abandonment of promising new therapeutics
      based on a false-negative imaging biomarker response being mistaken for a true
      negative.

PMID- 22596238
TI  - The relationships between cellular components of the peritumoural inflammatory
      response, clinicopathological characteristics and survival in patients with
      primary operable colorectal cancer.
AB  - BACKGROUND: The host inflammatory response is an important determinant of cancer
      outcome. We examined different methods of assessing the local inflammatory
      response in colorectal tumours and explored relationships with both
      clinicopathological characteristics and survival. METHODS: Cohort study of
      patients (n=130) with primary operable colorectal cancer and mature follow-up.
      Local inflammatory response at the invasive margin was assessed with: (1) a semi
      quantitative assessment of peritumoural inflammation using Klintrup-Makinen (K-M)
      grading and (2) an assessment of individual immune cell infiltration
      (lymphocytes, plasma cells, neutrophils, macrophages and eosinophils). RESULTS:
      The peritumoural inflammatory response was K-M low grade in 48% and high grade in
      52%. Inflammatory cells were primarily macrophages, lymphocytes and neutrophils
      with relatively few plasma cells or eosinophils. On univariate analysis, K-M
      grade, lymphocyte infiltration and plasma cell infiltration were associated with
      cancer-specific survival. On multivariate analysis, only systemic inflammatory
      response, TNM (tumour, node and metastases) stage, venous invasion, tumour
      necrosis and K-M grade were independently associated with cancer-specific
      survival. There was no relationship between local infiltration of inflammatory
      cells and a systemic inflammatory response. However, high K-M grade, lymphocyte
      infiltration and plasma cell infiltration were associated with a number of
      favourable pathological characteristics, including an absence of venous invasion.
      CONCLUSION: Infiltration of inflammatory cells in the invasive margin of
      colorectal tumours is beneficial to survival. The adaptive immune response
      appears to have a prominent role in the prevention of tumour progression in
      patients with colorectal cancer.

PMID- 22596239
TI  - The role of mesenchymal stem cells in anti-cancer drug resistance and tumour
      progression.
AB  - It is becoming increasingly clear that the tumour microenvironment has a very
      important role in tumour progression and drug resistance. Many different cell
      types within the tumour stroma have an effect on tumour progression either in a
      positive or in a negative way. Mesenchymal stem cells (MSCs) are a distinct
      population of cells that have been linked with tumour growth. Mesenchymal stem
      cells can home to tumours where they modulate the immune system and facilitate
      tumour growth, angiogenesis and metastasis. Recent studies have shown that MSCs
      also have an important role in the resistance to various anti-cancer drugs. This
      mini-review provides an overview of the functional properties of MSCs in tumour
      progression and drug resistance.

PMID- 22596240
TI  - Expression of MAGE-A3, NY-ESO-1, LAGE-1 and PRAME in urothelial carcinoma.
AB  - BACKGROUND: The potential for cancer-testis (CT) antigens as targets for
      immunotherapy in cancer patients has been heavily investigated, and currently
      cancer vaccine trials based on the CT antigens, MAGE-A3 and NY-ESO-1, are being
      carried out. METHODS: We used specific q-RT-PCR assays to analyse the expression
      of the CT genes MAGE-A3, NY-ESO-1 (CTAG1B), LAGE-1 (CTAG2) and PRAME in a panel
      of bladder tumours from 350 patients with long-term follow-up and detailed
      treatment information. RESULTS: Overall, 43% of the tumours expressed MAGE-A3,
      35% expressed NY-ESO-1, 27% expressed LAGE-1 and 20% expressed PRAME. In all, 56%
      of the tumours expressed at least one of the CT genes analysed. Univariate Cox
      regression analysis of CT gene expression in non-muscle-invasive tumours showed
      that expression of MAGE-A3 (P=0.026), LAGE-1 (P=0.001) and NY-ESO-1 (P=0.040) was
      significantly associated with a shorter progression-free survival. In addition,
      we found that patients with tumours expressing PRAME responded poorly to
      chemotherapy (P=0.02, chi(2)-test). CONCLUSION: Cancer-testis genes are
      frequently expressed in bladder cancer and especially in tumours of high stage
      and grade. In addition, the CT gene expression may have both prognostic and
      predictive value. Development of specific immunotherapy against the CT antigens
      in bladder cancer may ultimately increase patient survival.

PMID- 22596241
TI  - In vitro analysis of ovarian cancer response to cisplatin, carboplatin, and
      paclitaxel identifies common pathways that are also associated with overall
      patient survival.
AB  - BACKGROUND: Carboplatin and cisplatin, alone or in combination with paclitaxel,
      have similar efficacies against ovarian cancer (OVCA) yet exhibit different
      toxicity profiles. We characterised the common and unique cellular pathways that
      underlie OVCA response to these drugs and analyse whether they have a role in
      OVCA survival. METHODS: Ovarian cancer cell lines (n=36) were treated with
      carboplatin, cisplatin, paclitaxel, or carboplatin-paclitaxel (CPTX). For each
      cell line, IC(50) levels were quantified and pre-treatment gene expression
      analyses were performed. Genes demonstrating expression/IC(50) correlations
      (measured by Pearson; P<0.01) were subjected to biological pathway analysis. An
      independent OVCA clinico-genomic data set (n=142) was evaluated for clinical
      features associated with represented pathways. RESULTS: Cell line sensitivity to
      carboplatin, cisplatin, paclitaxel, and CPTX was associated with the expression
      of 77, 68, 64, and 25 biological pathways (P<0.01), respectively. We found three
      common pathways when drug combinations were compared. Expression of one pathway
      ('Transcription/CREB pathway') was associated with OVCA overall survival.
      CONCLUSION: The identification of the Transcription/CREB pathway (associated with
      OVCA cell line platinum sensitivity and overall survival) could improve patient
      stratification for treatment with current therapies and the rational selection of
      future OVCA therapy agents targeted to these pathways.

PMID- 22596242
TI  - Histological confirmation of breast cancer registration and self-reporting in
      England and Wales: a cohort study within the UK Collaborative Trial of Ovarian
      Cancer Screening.
AB  - BACKGROUND: In research studies, accurate information of cancer diagnosis is
      crucial. In women with breast cancer (BC), we compare cancer registration (CR) in
      England/Wales and self-reporting with independent confirmation. METHODS: In the
      UK Collaborative Trial of Ovarian Cancer Screening, notification of BC diagnosed
      between randomisation and 31 December 2009 was obtained through (1) CR (17
      October 2011) and (2) self-reporting using postal-questionnaire. Breast cancer
      was confirmed using a detailed questionnaire (BC questionnaire BCQ) completed by
      the treating clinician (gold standard). Apparent sensitivity and positive
      predictive value of CR/self-reporting vs BCQ were calculated. RESULTS: Of 1065
      women with possible BC notification, diagnosis was confirmed in 932 (87.5%). A
      total of 3.1% (28 out of 918) of BC CR and 12.4% (128 out of 1032) of women with
      self-reported BC only had in-situ carcinoma on BCQ. Another 4.6% (43 out of 932)
      of BCQ-confirmed cancer did not have a BC registration, and 3.6% (34 out of 932)
      did not self-report BC. Apparent sensitivity of CR and self-reporting vs BCQ were
      95.4 and 96.4%, respectively. Positive-predictive value of self-reporting (87.1%)
      was significantly lower than that of CR (96.8%). Women aged<65 were more likely
      to over report in-situ carcinoma as BC. Overall, 73 (6.8%) women would have been
      misclassified/missed if CR, and 167 (15.6%) if self-reporting data alone was
      used. CONCLUSION: This study confirms the reliability of BC registration in
      England/Wales and highlights the fact that 1 in 10 women self-reporting BC might
      only have in-situ breast carcinoma.

PMID- 22596244
TI  - Acute rhinosinusitis--does quality of life explain continued rates of antibiotic
      overusage?

PMID- 22596243
TI  - Integrated rapid-diagnostic-test reader platform on a cellphone.
AB  - We demonstrate a cellphone-based rapid-diagnostic-test (RDT) reader platform that
      can work with various lateral flow immuno-chromatographic assays and similar
      tests to sense the presence of a target analyte in a sample. This compact and
      cost-effective digital RDT reader, weighing only ~65 g, mechanically attaches to
      the existing camera unit of a cellphone, where various types of RDTs can be
      inserted to be imaged in reflection or transmission modes under light-emitting
      diode (LED)-based illumination. Captured raw images of these tests are then
      digitally processed (within less than 0.2 s per image) through a smart
      application running on the cellphone for validation of the RDT, as well as for
      automated reading of its diagnostic result. The same smart application then
      transmits the resulting data, together with the RDT images and other related
      information (e.g., demographic data), to a central server, which presents the
      diagnostic results on a world map through geo-tagging. This dynamic spatio
      temporal map of various RDT results can then be viewed and shared using internet
      browsers or through the same cellphone application. We tested this platform using
      malaria, tuberculosis (TB) and HIV RDTs by installing it on both Android-based
      smartphones and an iPhone. Providing real-time spatio-temporal statistics for the
      prevalence of various infectious diseases, this smart RDT reader platform running
      on cellphones might assist healthcare professionals and policymakers to track
      emerging epidemics worldwide and help epidemic preparedness.

PMID- 22596245
TI  - Is hospitalisation for COPD an opportunity for advance care  planning? A
      qualitative study.
AB  - BACKGROUND: It is recognised that patients with chronic obstructive pulmonary
      disease (COPD) should have the chance to discuss end-of-life care and advance
      care planning (ACP). Admission to hospital with an exacerbation may be a possible
      opportunity. AIMS: To examine whether an admission to hospital for an
      exacerbation of COPD is an opportunity for ACP and to understand, from the
      patient perspective, the optimum circumstances for ACP. METHODS: Patients who had
      a recent admission for an exacerbation of COPD were identified. Sixteen patients
      and their carers were interviewed. The interviews were analysed using qualitative
      methodology. RESULTS: No patients recalled discussions about resuscitation or
      planning for the future. Hospital admission and discharge was seen as chaotic and
      lacking in continuity. Some patients welcomed the opportunity to discuss ACP and
      felt that their general practitioner (GP) would be the best person for this.
      Others wished to avoid end-of-life care discussions but there was evidence that,
      with empathetic and knowledgeable support, these discussions could be initiated.
      CONCLUSIONS: The period of hospitalisation may not be an appropriate time to
      initiate ACP but may be a milestone that can lead to discussions. GPs should be
      alert to that opportunity after discharge from hospital.

PMID- 22596246
TI  - Obesity, airflow limitation, and respiratory symptoms: does it take three to
      tango?

PMID- 22596247
TI  - Streptococcus pyogenes upper respiratory infections and their effect on atopic
      conditions.

PMID- 22596248
TI  - Testing for growth hormone deficiency in adults:  doing without growth hormone
      releasing hormone.
AB  - PURPOSE OF REVIEW: This article summarizes recent advances in testing for growth
      hormone deficiency (GHD) in adults, focusing on critical appraisal of existing
      growth hormone (GH) provocative tests as well as newer tests in development.
      RECENT FINDINGS: The diagnosis of GHD can be challenging and often requires the
      use of GH provocative testing. The most widely validated of these is insulin
      induced hypoglycemia (ITT), which requires close supervision and has significant
      contraindications and side-effects. The arginine-growth hormone-releasing hormone
      (GHRH) test had become widely used as a safe and accurate alternative to the ITT,
      but GHRH is currently unavailable for clinical use in the USA. On the basis of
      review of recent literature we recommend that in the absence of GHRH, glucagon
      stimulation testing should be the preferred alternative to ITT. Several synthetic
      GH secretagogues that mimic the gastric peptide ghrelin are currently in
      development and may become available for use in the diagnosis of GHD in the near
      future. Other GH provocative tests suitable for use in children lack adequate
      specificity for the diagnosis of GHD in adults. SUMMARY: Due to the current
      unavailability of the arginine-GHRH test in the USA, when ITT is contraindicated
      or impractical we recommend the glucagon stimulation testing as the GH
      provocative test of choice. There remains a need for a simple, safe and accurate
      test for the diagnosis of GHD.

PMID- 22596249
TI  - Akt promotes post-irradiation survival of human tumor cells through initiation,
      progression, and termination of DNA-PKcs-dependent DNA double-strand break
      repair.
AB  - Akt phosphorylation has previously been described to be involved in mediating DNA
      damage repair through the nonhomologous end-joining (NHEJ) repair pathway. Yet
      the mechanism how Akt stimulates DNA-protein kinase catalytic subunit (DNA-PKcs)
      dependent DNA double-strand break (DNA-DSB) repair has not been described so far.
      In the present study, we investigated the mechanism by which Akt can interact
      with DNA-PKcs and promote its function during the NHEJ repair process. The
      results obtained indicate a prominent role of Akt, especially Akt1 in the
      regulation of NHEJ mechanism for DNA-DSB repair. As shown by pull-down assay of
      DNA-PKcs, Akt1 through its C-terminal domain interacts with DNA-PKcs. After
      exposure of cells to ionizing radiation (IR), Akt1 and DNA-PKcs form a functional
      complex in a first initiating step of DNA-DSB repair. Thereafter, Akt plays a
      pivotal role in the recruitment of AKT1/DNA-PKcs complex to DNA duplex ends
      marked by Ku dimers. Moreover, in the formed complex, Akt1 promotes DNA-PKcs
      kinase activity, which is the necessary step for progression of DNA-DSB repair.
      Akt1-dependent DNA-PKcs kinase activity stimulates autophosphorylation of DNA
      PKcs at S2056 that is needed for efficient DNA-DSB repair and the release of DNA
      PKcs from the damage site. Thus, targeting of Akt results in radiosensitization
      of DNA-PKcs and Ku80 expressing, but not of cells deficient for, either of these
      proteins. The data showed indicate for the first time that Akt through an
      immediate complex formation with DNA-PKcs can stimulate the accumulation of DNA
      PKcs at DNA-DSBs and promote DNA-PKcs activity for efficient NHEJ DNA-DSB repair.

PMID- 22596250
TI  - Bone diseases: SEMA3A strikes a balance in bone homeostasis.

PMID- 22596251
TI  - Neurological disorders: Nanoparticle opens door to cerebral palsy treatment.

PMID- 22596252
TI  - Infectious disease: Pro-resolving lipids offer a helping hand to antibiotics.

PMID- 22596254
TI  - A blueprint for an ideal corporate information centre.

PMID- 22596253
TI  - Neuropeptide receptor ligands as drugs for psychiatric diseases: the end of the
      beginning?
AB  - The search for novel drugs for treating psychiatric disorders is driven by the
      growing medical need to improve on the effectiveness and side-effect profile of
      currently available therapies. Given the wealth of preclinical data supporting
      the role of neuropeptides in modulating behaviour, pharmaceutical companies have
      been attempting to target neuropeptide receptors for over two decades. However,
      clinical studies with synthetic neuropeptide ligands have been unable to confirm
      the promise predicted by studies in animal models. Here, we analyse preclinical
      and clinical results for neuropeptide receptor ligands that have been studied in
      clinical trials for psychiatric diseases, including agents that target the
      receptors for tachykinins, corticotropin-releasing factor, vasopressin and
      neurotensin, and suggest new ways to exploit the full potential of these
      candidate drugs.

PMID- 22596256
TI  - Probing the binding of two sugar bearing anticancer agents aristololactam-beta
      (D)-glucoside and daunomycin to double stranded RNA polynucleotides: a combined
      spectroscopic and calorimetric study.
AB  - The plant alkaloid aristololactam-beta-d-glucoside and the anticancer
      chemotherapy drug daunomycin are two sugar bearing DNA binding antibiotics. The
      binding of these molecules to three double stranded ribonucleic acids,
      poly(A).poly(U), poly(I).poly(C) and poly(C).poly(G), was studied using various
      biophysical techniques. Absorbance and fluorescence studies revealed that these
      molecules bound non-cooperatively to these ds RNAs with the binding affinities of
      the order 10(6) for daunomycin and 10(5) M(-1) for aristololactam-beta-d
      glucoside. Fluorescence quenching and viscosity studies gave evidence for
      intercalative binding. The binding enhanced the melting temperature of
      poly(A).poly(U) and poly(I).poly(C) and the binding affinity values evaluated
      from the melting data were in agreement with that obtained from other techniques.
      Circular dichroism results suggested minor conformational perturbations of the
      RNA structures. The binding was characterized by negative enthalpy and positive
      entropy changes and the affinity constants derived from calorimetry were in
      agreement with that obtained from spectroscopic data. Daunomycin bound all the
      three RNAs stronger than aristololactam-beta-d-glucoside and the binding affinity
      varied as poly(A).poly(U) > poly(I).poly(C) > poly(C).poly(G). The temperature
      dependence of the enthalpy changes yielded negative values of heat capacity
      changes for the complexation suggesting substantial hydrophobic contribution to
      the binding process. Furthermore, an enthalpy-entropy compensation behavior was
      also seen in all systems. These results provide new insights into binding of
      these small molecule drugs to double stranded RNA sequences.

PMID- 22596257
TI  - A perspective on the selection of unrelated donors and cord blood units for
      transplantation.
AB  - Selection of a suitable graft for allogeneic hematopoietic stem cell
      transplantation involves consideration of both donor and recipient
      characteristics. Of primary importance is sufficient donor-recipient HLA matching
      to ensure engraftment and acceptable rates of GVHD. In this Perspective, the
      National Marrow Donor Program and the Center for International Blood and Marrow
      Transplant Research provide guidelines, based on large studies correlating graft
      characteristics with clinical transplantation outcomes, on appropriate typing
      strategies and matching criteria for unrelated adult donor and cord blood graft
      selection.

PMID- 22596258
TI  - WHIM syndrome caused by a single amino acid substitution in the carboxy-tail of
      chemokine receptor CXCR4.
AB  - WHIM syndrome is a rare, autosomal dominant, immunodeficiency disorder so-named
      because it is characterized by warts, hypogammaglobulinemia, infections, and
      myelokathexis (defective neutrophil egress from the BM). Gain-of-function
      mutations that truncate the C-terminus of the chemokine receptor CXCR4 by 10-19
      amino acids cause WHIM syndrome. We have identified a family with autosomal
      dominant inheritance of WHIM syndrome that is caused by a missense mutation in
      CXCR4, E343K (1027G -> A). This mutation is also located in the C-terminal
      domain, a region responsible for negative regulation of the receptor.
      Accordingly, like CXCR4(R334X), the most common truncation mutation in WHIM
      syndrome, CXCR4(E343K) mediated approximately 2-fold increased signaling in
      calcium flux and chemotaxis assays relative to wild-type CXCR4; however,
      CXCR4(E343K) had a reduced effect on blocking normal receptor down-regulation
      from the cell surface. Therefore, in addition to truncating mutations in the C
      terminal domain of CXCR4, WHIM syndrome may be caused by a single charge-changing
      amino acid substitution in this domain, E343K, that results in increased receptor
      signaling.

PMID- 22596255
TI  - The nonskeletal effects of vitamin D: an Endocrine Society scientific statement.
AB  - Significant controversy has emerged over the last decade concerning the effects
      of vitamin D on skeletal and nonskeletal tissues. The demonstration that the
      vitamin D receptor is expressed in virtually all cells of the body and the
      growing body of observational data supporting a relationship of serum 25
      hydroxyvitamin D to chronic metabolic, cardiovascular, and neoplastic diseases
      have led to widespread utilization of vitamin D supplementation for the
      prevention and treatment of numerous disorders. In this paper, we review both the
      basic and clinical aspects of vitamin D in relation to nonskeletal organ systems.
      We begin by focusing on the molecular aspects of vitamin D, primarily by
      examining the structure and function of the vitamin D receptor. This is followed
      by a systematic review according to tissue type of the inherent biological
      plausibility, the strength of the observational data, and the levels of evidence
      that support or refute an association between vitamin D levels or supplementation
      and maternal/child health as well as various disease states. Although
      observational studies support a strong case for an association between vitamin D
      and musculoskeletal, cardiovascular, neoplastic, and metabolic disorders, there
      remains a paucity of large-scale and long-term randomized clinical trials. Thus,
      at this time, more studies are needed to definitively conclude that vitamin D can
      offer preventive and therapeutic benefits across a wide range of physiological
      states and chronic nonskeletal disorders.

PMID- 22596259
TI  - Osteoblastic N-cadherin is not required for microenvironmental support and
      regulation of hematopoietic stem and progenitor cells.
AB  - Hematopoietic stem cell (HSC) regulation is highly dependent on interactions with
      the marrow microenvironment. Controversy exists on N-cadherin's role in support
      of HSCs. Specifically, it is unknown whether microenvironmental N-cadherin is
      required for normal marrow microarchitecture and for hematopoiesis. To determine
      whether osteoblastic N-cadherin is required for HSC regulation, we used a genetic
      murine model in which deletion of Cdh2, the gene encoding N-cadherin, has been
      targeted to cells of the osteoblastic lineage. Targeted deletion of N-cadherin
      resulted in an age-dependent bone phenotype, ultimately characterized by
      decreased mineralized bone, but no difference in steady-state HSC numbers or
      function at any time tested, and normal recovery from myeloablative injury.
      Intermittent parathyroid hormone (PTH) treatment is well established as anabolic
      to bone and to increase marrow HSCs through microenvironmental interactions. Lack
      of osteoblastic N-cadherin did not block the bone anabolic or the HSC effects of
      PTH treatment. This report demonstrates that osteoblastic N-cadherin is not
      required for regulation of steady-state hematopoiesis, HSC response to
      myeloablation, or for rapid expansion of HSCs through intermittent treatment with
      PTH.

PMID- 22596260
TI  - Platelets and platelet-like particles mediate intercellular RNA transfer.
AB  - The role of platelets in hemostasis and thrombosis is clearly established;
      however, the mechanisms by which platelets mediate inflammatory and immune
      pathways are less well understood. Platelets interact and modulate the function
      of blood and vascular cells by releasing bioactive molecules. Although the
      platelet is anucleate, it contains transcripts that may mirror disease. Platelet
      mRNA is only associated with low-level protein translation; however, platelets
      have a unique membrane structure allowing for the passage of small molecules,
      leading to the possibility that its cytoplasmic RNA may be passed to nucleated
      cells. To examine this question, platelet-like particles with labeled RNA were
      cocultured with vascular cells. Coculture of platelet-like particles with
      activated THP-1, monocytic, and endothelial cells led to visual and functional
      RNA transfer. Posttransfer microarray gene expression analysis of THP-1 cells
      showed an increase in HBG1/HBG2 and HBA1/HBA2 expression that was directly
      related to the transfer. Infusion of wild-type platelets into a TLR2-deficient
      mouse model established in vivo confirmation of select platelet RNA transfer to
      leukocytes. By specifically transferring green fluorescent protein, we also
      observed external RNA was functional in the recipient cells. The observation that
      platelets possess the capacity to transfer cytosolic RNA suggests a new function
      for platelets in the regulation of vascular homeostasis.

PMID- 22596261
TI  - CD62L- memory T cells enhance T-cell regeneration after allogeneic stem cell
      transplantation by eliminating host resistance in mice.
AB  - A major challenge in allogeneic hematopoietic cell transplantation is how to
      transfer T-cell immunity without causing graft-versus-host disease (GVHD).
      Effector memory T cells (CD62L(-)) are a cell subset that can potentially address
      this challenge because they do not induce GVHD. Here, we investigated how CD62L(
      ) T cells contributed to phenotypic and functional T-cell reconstitution after
      transplantation. On transfer into allogeneic recipients, CD62L(-) T cells were
      activated and expressed multiple cytokines and cytotoxic molecules. CD62L(-) T
      cells were able to deplete host radioresistant T cells and facilitate
      hematopoietic engraftment, resulting in enhanced de novo T-cell regeneration.
      Enhanced functional immune reconstitution was demonstrated in CD62L(-) T-cell
      recipients using a tumor and an influenza virus challenge model. Even though
      CD62L(-) T cells are able to respond to alloantigens and deplete host
      radioresistant immune cells in GVHD recipients, alloreactive CD62L(-) T cells
      lost the reactivity over time and were eventually tolerant to alloantigens as a
      result of prolonged antigen exposure, suggesting a mechanism by which CD62L(-) T
      cells were able to eliminate host resistance without causing GVHD. These data
      further highlight the unique characteristics of CD62L(-) T cells and their
      potential applications in clinical hematopoietic cell transplantation.

PMID- 22596263
TI  - Tic disorders: what happens in the basal ganglia?
AB  - Motor tics are brief, repetitive, involuntary movements that interfere with
      behavior and appear in multiple neural disorders, most notably, Tourette
      syndrome. Converging evidence from different lines of research point to the
      involvement of the corticobasal ganglia system in tics, but the neural mechanism
      underlying motor tics is largely unknown. An animal model directly linking basal
      ganglia dysfunction and motor tics indicated that local disinhibition within the
      basal ganglia input structure, the striatum, induces the appearance of motor tics
      in both rats and monkeys. Recordings of neuronal activity from multiple brain
      regions performed in this model during the expression of motor tics showed that
      tics are associated with phasic changes of neuronal activity throughout the
      corticobasal ganglia pathway, culminating in the disinhibition of the cortex and
      the release of a tic. This line of research provides a mechanistic description of
      the underlying neurophysiology of motor tics and may supply the much needed
      infrastructure for methodical hypothesis-driven studies of novel clinical
      treatments.

PMID- 22596262
TI  - Extracellular DNA traps are associated with the pathogenesis of TRALI in humans
      and mice.
AB  - Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion
      related death. The biologic processes contributing to TRALI are poorly
      understood. All blood products can cause TRALI, and no specific treatment is
      available. A "2-event model" has been proposed as the trigger. The first event
      may include surgery, trauma, or infection; the second involves the transfusion of
      antileukocyte antibodies or bioactive lipids within the blood product. Together,
      these events induce neutrophil activation in the lungs, causing endothelial
      damage and capillary leakage. Neutrophils, in response to pathogens or under
      stress, can release their chromatin coated with granule contents, thus forming
      neutrophil extracellular traps (NETs). Although protective against infection,
      these NETs are injurious to tissue. Here we show that NET biomarkers are present
      in TRALI patients' blood and that NETs are produced in vitro by primed human
      neutrophils when challenged with anti-HNA-3a antibodies previously implicated in
      TRALI. NETs are found in alveoli of mice experiencing antibody-mediated TRALI.
      DNase 1 inhalation prevents their alveolar accumulation and improves arterial
      oxygen saturation even when administered 90 minutes after TRALI onset. We suggest
      that NETs form in the lungs during TRALI, contribute to the disease process, and
      thus could be targeted to prevent or treat TRALI.

PMID- 22596264
TI  - Riluzole: what it does to spinal and brainstem neurons and how it does it.
AB  - Amyotrophic lateral sclerosis (Lou Gehrig's disease) is a devastating
      neurodegenerative disorder for which the only licensed treatment is riluzole.
      Although riluzole clinical efficacy is rather limited, its use has important
      implications for identifying those parameters that might improve its clinical
      benefits (dose, timing, disease stage) and for its off-label administration in
      other neurodegenerative diseases, such as spinal cord injury. Studies of riluzole
      also have an intrinsically heuristic value to unveil mechanisms regulating the
      excitability of brain and spinal neurons because this drug is a pharmacological
      tool to probe the function of certain ion channels, or to study neurotransmitter
      release processes, and intracellular neuroprotective pathways. The present review
      focuses on how riluzole acts on brain and spinal neurons within motor networks,
      what mechanisms can be deduced from its effects, and what conditions may favor
      its use to contrast neurodegeneration or to ameliorate late symptoms like
      spasticity. Taking as an example the experimental neurodegeneration caused by
      overactivation of glutamatergic synapses (excitotoxicity), it seems likely that
      protection of motor networks by riluzole involves selected administration timing
      and dosing to target processes for releasing glutamate from very active synapses
      or for dampening repetitive firing by hyperfunctional motor cells.

PMID- 22596265
TI  - Ethical conduct of humanitarian medical missions: I. Informed Consent.
AB  - Altruistic and socially conscious physicians are dedicating a portion of their
      professional lives to humanitarian relief of disadvantaged populations in
      increasing numbers. These efforts are primarily carried out through short-term
      medical missions(STMMs) throughout the international community.(1) There is a
      great deal of professional and personal reward to physicians who participate in
      medical missions, and their experiences as related to colleagues may serve to
      encourage others to participate as well. Indeed, there is an increasing interest
      in, and enthusiasm for, medical students to participate in international
      volunteer electives during medical school, particularly in developing countries.
      Their positive experiences often shape their future commitment to volunteerism as
      a physician.(2)

PMID- 22596266
TI  - Apolipoprotein E genotype: the innocent bystander or active bridge between
      metabolic syndrome and cognitive impairment?
AB  - Apolipoprotein E [ApoE, APOE (gene)] is a multifunctional protein of the lipid
      and lipoprotein transport system mainly involved in metabolism of dietary lipids.
      Its polymorphic variants are considered a genetic risk factor of cognitive
      impairment in several neurodegenerative disorders such as Lewy body dementia,
      Huntington's disease, and Alzheimer's disease, as well as in vascular dementia
      and cerebrovascular disease. The precise mechanism by which APOE affects
      neurodegeneration is still unclear. Epidemiological and experimental studies
      demonstrated an influence of APOE on metabolic parameters but, to the best of our
      knowledge, no data are available about the exact role in humans of the effect of
      APOE on metabolic-cognitive syndrome (MCS). The latter is a model of cognitive
      impairment linked to metabolic syndrome identifying a grey zone between metabolic
      disorders and neuropathological process driving late-life cognitive decline.
      Although it may be a daring project that does not reach a final conclusion
      because of disease complexity, I hope to elucidate whether APOE may have a
      prominent role in MCS, going beyond the simple addition of separate mechanisms
      already known.

PMID- 22596267
TI  - [11C]-MP4A PET cholinergic measurements in amnestic mild cognitive impairment,
      probable Alzheimer's disease, and dementia with Lewy bodies: a Bayesian method
      and voxel-based analysis.
AB  - Non-invasive approaches for positron emission tomography (PET) parametric imaging
      of acetylcholinesterase (AChE) activity have been developed and applied to the
      investigation of dementia, mainly Alzheimer's disease (AD), but also dementia
      with Lewy bodies (DLB), not including, however, patients in the early disease
      stage. The few cholinergic PET studies on mild cognitive impairment (MCI) did not
      provide clinical follow-up. One limitation of the methods used so far is the
      relatively low sensitivity in measuring subcortical or deep cortical structures,
      which might represent specific disease markers. Here we assessed AChE activity
      with [11C]-MP4A and PET by a maximum a posteriori Bayesian method (MAPB) based on
      a 2-tissue compartment-3-rate-constant reference region model. 30 subjects were
      included: 10 multi-domain amnestic MCI (aMCI) with a follow up of 2 years, 7
      probable AD (pAD), 4 DLB subjects, and 9 healthy controls. Regions of interest
      and voxel-based statistical parametric mapping analyses revealed significant and
      widespread AChE reductions in several cortical regions and in the hippocampus in
      all pAD subjects and aMCI subjects who progressed to AD (converters). Noteworthy,
      hippocampal AChE activity correlated significantly with long-term verbal and non
      verbal memory in both aMCI converters and pAD. The pattern was more heterogeneous
      in early DLB patients, with only 2 out of 4 cases showing a severe or
      intermediate reduction of AChE activity. The comparable AChE reductions in pAD
      and aMCI converters indicate the presence of a widespread impairment of the
      cholinergic system already in the MCI phase. A more variable degree of
      cholinergic dysfunction is present in early DLB.

PMID- 22596268
TI  - Biochemical studies of poly-T variants in the Alzheimer's disease associated
      TOMM40 gene.
AB  - The apolipoprotein E (APOE) gene remains the most strongly established risk
      factor for late onset Alzheimer's disease (LOAD). Recently the gene, TOMM40,
      which is in linkage disequilibrium with APOE, was identified to be associated
      with LOAD in genome-wide association studies. One of the identified polymorphisms
      in TOMM40 is rs10524523, which is located in intron 6 and composed of thymidine
      repeats varying between 14 to 36 base-pairs in length. Reported results are
      contradictory in regard to the very long poly-T variant that has been associated
      with both increased and decreased risk of LOAD. Our study aimed to elucidate the
      functional implication of rs10524523 in an in vitro model of human fibroblast
      cells obtained from cognitively healthy APOE epsilon3/epsilon4 carriers harboring
      very long or short poly-T variants coupled to their APOE epsilon3 allele. We have
      studied (i) expression levels of TOM40 protein and mRNA, (ii) TOM40 mRNA
      splicing, and (iii) mitochondrial function and morphology; and we have found no
      significant differences in regards to very long or short poly-T variant.

PMID- 22596269
TI  - Metabolic-cognitive syndrome: metabolic approach for the management of
      Alzheimer's disease risk.

PMID- 22596270
TI  - Tau triage decisions mediated by the chaperone network.
AB  - The pathological accumulation of the microtubule-binding protein tau is linked to
      an increasing number of neurodegenerative conditions associated with aging,
      though the mechanisms by which tau accumulates in disease are unclear. In this
      review, we will summarize our previous research assessing the mechanism of
      action, as well as the therapeutic potential of Hsp90 inhibition for the
      treatment of tauopathies. Specifically, we describe the development of a high
      throughput screening approach to identify and rank compounds, and demonstrate the
      selective elimination of aberrant p-tau species in the brain following treatment
      with an Hsp90 inhibitor. Additionally, we identify CHIP as an essential component
      of the Hsp90 chaperone complex that mediates tau degradation, and present
      evidence to suggest that CHIP functions to identify and sequester neurotoxic tau
      species. Finally, we discuss recent data identifying an additional mechanism by
      which CHIP modulates protein triage decisions involving Hsp90. Specifically, CHIP
      indirectly regulates Hsp90 chaperone activity by modulating steady-state levels
      of the Hsp90 deacetylase, HDAC6, thus influencing both the acetylation state and
      function of Hsp90. Thus future research directions will focus on the manipulation
      of this network to promote degradation of pathogenic tau species in disease.

PMID- 22596271
TI  - Distinct functional activity of the precuneus and posterior cingulate cortex
      during encoding in the preclinical stage of Alzheimer's disease.
AB  - In this study functional magnetic resonance imaging (fMRI) is used to investigate
      the functional brain activation pattern in the preclinical stage of AD (pre-AD)
      subjects during a visual encoding memory task. Thirty subjects, eleven in the pre
      AD stage, with decreased cerebrospinal fluid levels of Abeta42 (<500 pg/ml), and
      19 controls with normal Abeta42 levels (CTR) were included. fMRI was acquired
      during a visual encoding task. Data were analyzed through an Independent
      Component Analysis (ICA) and region-of-interest-based univariate analysis of task
      related BOLD signal change. From the ICA decomposition, we identified the main
      task-related component, which included the activation of visual associative areas
      and prefrontal executive regions, and the deactivation of the default-mode
      network. The activation was positively correlated with task performance in the
      CTR group (p < 0.0054). Within this pattern, subjects in the pre-AD stage had
      significantly greater activation of the precuneus and posterior cingulate cortex
      during encoding. Subjects in the pre-AD stage present distinct functional neural
      activity before the appearance of clinical symptomatology. These findings may
      represent that subtle changes in functional brain activity precede clinical and
      cognitive symptoms in the AD continuum. Present findings provide evidence
      suggesting that fMRI may be a suitable biomarker of preclinical AD.

PMID- 22596272
TI  - The brain-derived neurotrophic factor Val66Met polymorphism is associated with
      reduced hippocampus perfusion in frontotemporal lobar degeneration.
AB  - Brain-derived neurotrophic factor (BDNF) promotes several functions in neurons
      and modulates neurotransmissions, especially in hippocampal regions.
      Frontotemporal lobar degeneration (FTLD) has a strong genetic background, but
      genetic risk factors associated with sporadic disease are unknown. Hippocampal
      involvement is frequently observed in FTLD. The aims of this study were: i) to
      evaluate if BDNF genetic variations are associated with an increased risk of
      developing FTLD; and ii) to assess the neuroimaging profiles associated with BDNF
      polymorphisms. Ninety-one FTLD patients who underwent SPECT imaging and blood
      sampling entered the study, and clinical, cognitive, and behavioral examinations
      were performed. A larger group of FTLD patients (n = 194) and controls (n = 396;
      162 healthy subjects and 234 Alzheimer's disease (AD) patients) underwent genetic
      analyses, considering BDNF polymorphisms (Val66Met, rs2049045 C/G, G11757C). A
      significant different distribution of G11757C genotype in FTLD (GG 53.1%, GC
      42.8%, CC 4.1%) compared to controls (G/G 55.6%, G/C 34.6%, C/C 9.8%, p = 0.020)
      was found. No other significant differences in genotype and allele distributions
      were detected. The effect of BDNF polymorphisms on brain perfusion was analyzed.
      BDNF Val66Met A* carriers (A/A or G/A) showed a significant greater hypoperfusion
      parahippocampal regions as compared to G/G carriers (p < 0.005). No effect of
      G11757C polymorphism on brain perfusion was found. rs2049045 C/G was not
      considered as in linkage disequilibrium with Val66Met polymorphism. BDNF Val66Met
      polymorphism may play a role as a modulator of the FTLD expression and may drive
      a selective damage in specific brain region affected by the disease.

PMID- 22596273
TI  - RETRACTION of: Optimizing the exogenous antigen loading of monocyte-derived
      dendritic cells.

PMID- 22596288
TI  - Predictors of morbidity and mortality in acromegaly: an Italian survey.
AB  - OBJECTIVE: To describe demographic and hormonal characteristics, comorbidities
      (diabetes mellitus and hypertension), therapeutic procedures and their
      effectiveness, as well as predictors of morbidity and mortality in a nationwide
      survey of Italian acromegalic patients. DESIGN: Retrospective multicenter
      epidemiological study endorsed by the Italian Society of Endocrinology and
      performed in 24 tertiary referral Italian centers. The mean follow-up time was
      120 months. RESULTS: A total of 1512 patients, 41% male, mean age: 45+/-13 years,
      mean GH: 31+/-37 MUg/l, IGF1: 744+/-318 ng/ml, were included. Diabetes mellitus
      was reported in 16% of cases and hypertension in 33%. Older age and higher IGF1
      levels at diagnosis were significant predictors of diabetes and hypertension. At
      the last follow-up, 65% of patients had a controlled disease, of whom 55% were
      off medical therapy. Observed deaths were 61, with a standardized mortality ratio
      of 1.13 95% (confidence interval (CI): 0.87-1.46). Mortality was significantly
      higher in the patients with persistently active disease (1.93; 95% CI: 1.34
      2.70). Main causes of death were vascular diseases and malignancies with similar
      prevalence. A multivariate analysis showed that older age, higher GH at the last
      follow-up, higher IGF1 levels at diagnosis, malignancy, and radiotherapy were
      independent predictors of mortality. CONCLUSIONS: Pretreatment IGF1 levels are
      important predictors of morbidity and mortality in acromegaly. The full hormonal
      control of the disease, nowadays reached in the majority of patients with modern
      management, reduces greatly the disease-related mortality.

PMID- 22596317
TI  - US military medical missions in Iraq and Southeast Asia.

PMID- 22596320
TI  - The fate and future of patents on human genes and genetic diagnostic methods.
AB  - Since the 1970s, patents on human genes and genetic diagnostic methods have been
      granted under the assumption that they stimulate the development of diagnostic
      methods and therapeutic products. However, the principles and practices of
      patenting vary between jurisdictions. Do patent holders, researchers, clinicians
      and patients really benefit from this heterogeneous patent system? We discuss the
      problems that result from the current system and suggest how they might be solved
      by altering the way in which patents are granted and/or licensed.

PMID- 22596318
TI  - Foundations for the design and implementation of synthetic genetic circuits.
AB  - Synthetic gene circuits are designed to program new biological behaviour,
      dynamics and logic control. For all but the simplest synthetic phenotypes, this
      requires a structured approach to map the desired functionality to available
      molecular and cellular parts and processes. In other engineering disciplines, a
      formalized design process has greatly enhanced the scope and rate of success of
      projects. When engineering biological systems, a desired function must be
      achieved in a context that is incompletely known, is influenced by stochastic
      fluctuations and is capable of rich nonlinear interactions with the engineered
      circuitry. Here, we review progress in the provision and engineering of libraries
      of parts and devices, their composition into large systems and the emergence of a
      formal design process for synthetic biology.

PMID- 22596319
TI  - Maintaining differentiated cellular identity.
AB  - Various studies have demonstrated that somatic differentiated cells can be
      reprogrammed into other differentiated states or into pluripotency, thus showing
      that the differentiated cellular state is not irreversible. These findings have
      generated intense interest in the process of reprogramming and in mechanisms that
      govern the pluripotent state. However, the realization that differentiated cells
      can be triggered to switch to considerably different lineages also emphasizes
      that we need to understand how the identity of mature cells is normally
      maintained. Here we review recent studies on how the differentiated state is
      controlled at the transcriptional level and discuss how new insights have begun
      to elucidate mechanisms underlying the stable maintenance of mature cell
      identities.

PMID- 22596349
TI  - Poly(ADP-ribose) polymerase 1 modulates the lethality of CHK1 inhibitors in
      mammary tumors.
AB  - The present studies sought to define whether checkpoint kinase 1 (CHK1)
      inhibitors and poly(ADP-ribose) polymerase 1 (PARP1) inhibitors interact in vitro
      and in vivo to kill breast cancer cells. PARP1 and CHK1 inhibitors interacted to
      kill estrogen receptor (ER)+, ER+ fulvestrant-resistant, HER2+, or triple
      negative mammary carcinoma cells in a manner that was not apparently affected by
      phosphatase and tensin homolog deleted on chromosome 10 functional status.
      Expression of dominant-negative CHK1 enhanced and overexpression of wild-type
      CHK1 suppressed the toxicity of PARP1 inhibitors in a dose-dependent fashion.
      Knockdown of PARP1 enhanced the lethality of CHK1 inhibitors in a dose-dependent
      fashion. PARP1 and CHK1 inhibitors interacted in vivo both to suppress the growth
      of large established tumors and to suppress the growth of smaller developing
      tumors; the combination enhanced animal survival. PARP1 and CHK1 inhibitors
      profoundly radiosensitized cells in vitro and in vivo. In conclusion, our data
      demonstrate that the combination of PARP1 and CHK1 inhibitors has antitumor
      activity in vivo against multiple mammary tumor types and that translation of
      this approach could prove to be a useful anticancer therapeutic approach.

PMID- 22596350
TI  - Differential modulation of drug-induced structural and functional plasticity of
      dendritic spines.
AB  - Drug-induced plasticity of excitatory synapses has been proposed to be the
      cellular mechanism underlying the aberrant learning associated with addiction.
      Exposure to various drugs of abuse causes both morphological plasticity of
      dendritic spines and functional plasticity of excitatory synaptic transmission.
      Chronic activation of MU-opioid receptors (MOR) in cultured hippocampal neurons
      causes two forms of synaptic plasticity: loss of dendritic spines and loss of
      synaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
      receptors. With use of live imaging, patch-clamp electrophysiology, and
      immunocytochemistry, the present study reveals that these two forms of synaptic
      plasticity are mediated by separate, but interactive, intracellular signaling
      cascades. The inhibition of Ca(2+)/calmodulin-dependent protein kinase II with 1
      [N,O-bis(5-isoquinolinesulfonyl)-N-methyl-l-tyrosyl]-4-phenylpiperazine (KN-62)
      blocks MOR-mediated structural plasticity of dendritic spines, but not MOR
      mediated cellular redistribution of GluR1 and GluR2 AMPA receptor subunits. In
      contrast, the inhibition of calcineurin with tacrolimus (FK506) blocks both
      cellular processes. These findings support the idea that drug-induced structural
      and functional plasticity of dendritic spines is mediated by divergent, but
      interactive, signaling pathways.

PMID- 22596352
TI  - The effects of acute voluntary wheel running on recovery of function following
      medial frontal cortical contusions in rats.
AB  - PURPOSE: Traumatic brain injury (TBI) produces significant deficits in executive
      function, sensory-motor function, and on spatial learning tasks. We wish to study
      if recovery from TBI can be benefited by voluntary exercise. METHODS: A variation
      of the stop-signal reaction time (SSRT) task was employed to measure rats ability
      to obtain maximum reinforcers in a complex behavioral task. A 2 * 2 (lesion *
      treatment) experimental design was constructed with 31 weight restricted male
      Long-Evans rats which received either bilateral cortical contusions to the medial
      frontal cortex or sham preparations following the acquisition of the SSRT task
      (matched based on pre-surgical performance). Following surgery, rats were
      randomly assigned to either an environment with free access to running wheels or
      traditional single housing without running wheels. RESULTS: Rats receiving a
      bilateral TBI performed significantly worse than sham operated rats on a complex
      task. Contrary to our original hypothesis, acute exercise following injury
      exacerbated the deficits in the complex task that did not return to levels of the
      injured rats without access to running wheels until post-TBI day 13. CONCLUSION:
      We found a significant interaction between severe bilateral TBI and the
      introduction of voluntary exercise immediately post-injury. In this paradigm,
      voluntary wheel running exacerbated the TBI-induced deficit, rather than reducing
      it.

PMID- 22596351
TI  - Mapping the binding of GluN2B-selective N-methyl-D-aspartate receptor negative
      allosteric modulators.
AB  - We have used recent structural advances in our understanding of the N-methyl-d
      aspartate (NMDA) receptor amino terminal domain to explore the binding mode of
      multiple diaryl GluN2B-selective negative allosteric modulators at the interface
      between the GluN1 and GluN2B amino-terminal domains. We found that interaction of
      the A ring within the binding pocket seems largely invariant for a variety of
      structurally distinct ligands. In addition, a range of structurally diverse
      linkers between the two aryl rings can be accommodated by the binding site,
      providing a potential opportunity to tune interactions with the ligand binding
      pocket via changes in hydrogen bond donors, acceptors, as well as
      stereochemistry. The most diversity in atomic interactions between protein and
      ligand occur in the B ring, with functional groups that contain electron donors
      and acceptors providing additional atomic contacts within the pocket. A cluster
      of residues distant to the binding site also control ligand potency, the degree
      of inhibition, and show ligand-induced increases in motion during molecular
      dynamics simulations. Mutations at some of these residues seem to distinguish
      between structurally distinct ligands and raise the possibility that GluN2B
      selective ligands can be divided into multiple classes. These results should help
      facilitate the development of well tolerated GluN2B subunit-selective
      antagonists.

PMID- 22596353
TI  - Fast, accurate reaching movements with a visual-to-auditory sensory substitution
      device.
AB  - PURPOSE: Visual sensory substitution devices (SSDs) use sound or touch to convey
      information that is normally perceived by vision. The primary focus of prior
      research using SSDs was the perceptual components of learning to use SSDs and
      their neural correlates. However, sensorimotor integration is critical in the
      effort to make SSDs relevant for everyday tasks, like grabbing a cup of coffee
      efficiently. The purpose of this study was to test the use of a novel visual-to
      auditory SSD to guide a fast reaching movement. METHODS: Using sound, the SSD
      device relays location, shape and color information. Participants were asked to
      make fast reaching movements to targets presented by the SSD. RESULTS: After only
      a short practice session, blindfolded sighted participants performed fast and
      accurate movements to presented targets, which did not differ significantly from
      movements performed with visual feedback in terms of movement time, peak speed,
      and path length. A small but significant difference was found between the
      endpoint accuracy of movements under the two feedback conditions; remarkably, in
      both cases the average error was smaller than 0.5 cm. CONCLUSIONS: Our findings
      combine with previous brain-imaging studies to support a theory of a modality
      independent representation of spatial information. Task-specificity, rather than
      modality-specificity, of brain functions is crucially important for the
      rehabilitative use of SSDs in the blind and the visually impaired. We present the
      first direct comparison between movement trajectories performed with an SSD and
      ones performed under visual guidance. The accuracy level reached in this study
      demonstrates the potential applicability of using the visual-to-auditory SSD for
      performance of daily tasks which require fast, accurate reaching movements, and
      indicates a potential for rehabilitative use of the device.

PMID- 22596354
TI  - Vav deficiency impedes peripheral nerve regeneration in mice.
AB  - PURPOSE: The regeneration of adult peripheral nerves is a complex, multi-step
      process that is often incomplete, resulting in pain and/or loss of muscle
      innervation. Success is based on a fine-tuned interplay of neurons, Schwann
      cells, fibrocytes and macrophages realizing Wallerian degeneration, fiber
      regrowth and revascularization. Following trauma, the nerves distal to the injury
      site undergo Wallerian degeneration, an event that includes the phagocytosis of
      debris and the formation of Schwann cell scaffolds that guide the sprouting nerve
      fibers. The actin cytoskeleton is critical to all of these processes; therefore,
      activators of the cytoskeleton such as Rho GTPases and RhoGEFS such as Vav2 and
      Vav3 represent attractive targets for therapeutic intervention. METHODS: Sciatic
      nerve segments were surgically resected and reconstructed, and the
      degenerative/regenerative outcomes were compared in wild-type and Vav2/3 double
      knockout mice. RESULTS: Vav2/3 knockout nerves showed delayed Wallerian
      degeneration and revascularization, a broadly control-like morphometry of the
      regenerated nerves including remyelination, and contradictory motor function
      recovery, whereby impaired toe spreading was accompanied by enhanced muscle
      weight recreation. CONCLUSIONS: The data suggest that Vav2 and Vav3 are required
      for normal peripheral nerve degeneration/regeneration, revascularization and
      functional recovery. Functional redundancy, compensatory mechanisms, and muscle
      (pseudo)hypertrophy, however, impede the understanding of and intervention in Vav
      mediated processes.

PMID- 22596355
TI  - A non-brain penetrant PDE5A inhibitor improves functional recovery after stroke
      in rats.
AB  - PURPOSE: Phosphodiesterase 5A (PDE5A) inhibitors improve functional recovery in
      experimental models of stroke in rats when treatment is delayed and without
      effect on infarct volume. PDE5A is expressed to only a very limited extent in
      forebrain tissues, raising the possibility that the locus of effect for the
      inhibitors is outside the brain. To start to address this question, we determined
      whether PDE5A inhibitors must have the ability to cross the blood brain barrier
      to improve recovery. METHOD: After permanent middle cerebral artery occlusion in
      rats, PF-5 and UK-489,791, PDE5A inhibitors that do or do not pass the blood
      brain barrier, were administered starting 24 h after occlusion and continued for
      1 week. Motor function was assessed at intervals to 28 days using body swing and
      limb placement measures. RESULTS: Both PF-5 and UK-489,791 produced improvement
      in motor scores over 28 days that were significantly greater than in vehicle
      treated animals. There was no difference in efficacy between the two PDE5A
      inhibitors. CONCLUSIONS: Brain penetrability appears not to be critical to the
      ability of a PDE5A inhibitor to improve functional recovery after experimental
      stroke in rats. This finding is discussed with regard to the cellular target(s)
      for PDE5A inhibitors mediating this effect.

PMID- 22596356
TI  - Changes in cortical plasticity after mild traumatic brain injury.
AB  - PURPOSE: Even after a mild traumatic brain injury (TBI) symptoms may be long
      lasting and never resolve completely. The neurophysiologic substrate for such
      lasting deficits remains unclear. There is a lack of objective measures of early
      brain abnormalities following mild TBI, which could shed light on the genesis of
      these lasting impairments. METHODS: Here we report findings in a previously
      healthy man tested 2 and 6 weeks after a well-documented concussion. Findings
      were compared with 12 control subjects. All subjects underwent brain magnetic
      resonance imaging (MRI) and diffusion-tensor imaging (DTI). Testing included
      neuropsychological evaluation and physiological assessment with TMS and EEG,
      excitatory/inhibitory balance and brain plasticity. RESULTS: While the MRI, DTI
      and neuropsychological evaluations showed no abnormalities, neurophysiologic
      tests revealed subclinical abnormalities in our patient: (1) Significantly higher
      intracortical facilitation than the control group at both time points; (2)
      Intracortical inhibition presumably mediated by GABAB receptors was absent at
      week 2, but returned to normal value at week 6; (3) Abnormal mechanisms of
      plasticity at week 2, that normalize at week 6. CONCLUSIONS: These findings
      demonstrate a transient alteration of brain cortical physiology following
      concussion independent of anatomical findings and neuropsychological function.
      This case study suggests that TMS measures may serve as sensitive biomarkers of
      physiologic brain abnormalities after concussion.

PMID- 22596357
TI  - Excitability of intracortical inhibitory and facilitatory circuits during
      ischemic nerve block.
AB  - PURPOSE: The primary motor cortex is capable of rapid, reversible plastic changes
      and longer-term, more permanent reorganization. Ischemic nerve block (INB) is a
      model of deafferentation-induced short-term plasticity. We used transcranial
      magnetic stimulation to examine whether changes in the excitability of short-
      and/or long-interval intracortical inhibitory (SICI, LICI) or short-interval
      intracortical facilitatory (SICF) circuits underlie the corticospinal
      excitability increases observed during INB. METHODS: SICI and LICI recruitment
      curves, obtained by varying conditioning stimulus intensity, and SICF were
      measured at multiple inter-stimulus intervals (ISIs). RESULTS: Forearm flexor MEP
      amplitude increased during INB at the wrist; this was not accompanied by changes
      in SICI at ISIs of 1 or 2 ms, in SICF at ISIs of 1.2, 2.7, or 4.4 ms, or in LICI
      at an ISI of 80 ms, but was accompanied by an increase in LICI at an ISI of 150
      ms. CONCLUSIONS: The results suggest that (1) the increased excitability of
      forearm flexors is not due to reduced SICI or LICI or increased SICF, and (2)
      LICI measured at ISIs of 80 and 150 ms are distinct processes. We discuss the
      importance of identifying distinct processes of LICI and speculate regarding
      other mechanisms that could potentially underlie INB-induced plasticity.

PMID- 22596371
TI  - Social media and the EMJ.

PMID- 22596384
TI  - How should women be advised on weight management in pregnancy?

PMID- 22596383
TI  - Effects of interventions in pregnancy on maternal weight and obstetric outcomes:
      meta-analysis of randomised evidence.
AB  - OBJECTIVE: To evaluate the effects of dietary and lifestyle interventions in
      pregnancy on maternal and fetal weight and to quantify the effects of these
      interventions on obstetric outcomes. DESIGN: Systematic review and meta-analysis.
      DATA SOURCES: Major databases from inception to January 2012 without language
      restrictions. STUDY SELECTION: Randomised controlled trials that evaluated any
      dietary or lifestyle interventions with potential to influence maternal weight
      during pregnancy and outcomes of pregnancy. DATA SYNTHESIS: Results summarised as
      relative risks for dichotomous data and mean differences for continuous data.
      RESULTS: We identified 44 relevant randomised controlled trials (7278 women)
      evaluating three categories of interventions: diet, physical activity, and a
      mixed approach. Overall, there was 1.42 kg reduction (95% confidence interval
      0.95 to 1.89 kg) in gestational weight gain with any intervention compared with
      control. With all interventions combined, there were no significant differences
      in birth weight (mean difference -50 g, -100 to 0 g) and the incidence of large
      for gestational age (relative risk 0.85, 0.66 to 1.09) or small for gestational
      age (1.00, 0.78 to 1.28) babies between the groups, though by itself physical
      activity was associated with reduced birth weight (mean difference -60 g, -120 to
      -10 g). Interventions were associated with a reduced the risk of pre-eclampsia
      (0.74, 0.60 to 0.92) and shoulder dystocia (0.39, 0.22 to 0.70), with no
      significant effect on other critically important outcomes. Dietary intervention
      resulted in the largest reduction in maternal gestational weight gain (3.84 kg,
      2.45 to 5.22 kg), with improved pregnancy outcomes compared with other
      interventions. The overall evidence rating was low to very low for important
      outcomes such as pre-eclampsia, gestational diabetes, gestational hypertension,
      and preterm delivery. CONCLUSIONS: Dietary and lifestyle interventions in
      pregnancy can reduce maternal gestational weight gain and improve outcomes for
      both mother and baby. Among the interventions, those based on diet are the most
      effective and are associated with reductions in maternal gestational weight gain
      and improved obstetric outcomes.

PMID- 22596411
TI  - B cells: Selecting the best, without BCR signalling.

PMID- 22596412
TI  - Regulatory T cells: Stabilizing immune regulation in the gut.

PMID- 22596413
TI  - Innate immunity: AP3 links endosomal TLRs and antigen presentation.

PMID- 22596929
TI  - Alcohol drinking and overall and cause-specific mortality in China: nationally
      representative prospective study of 220,000 men with 15 years of follow-up.
AB  - BACKGROUND: Regular alcohol drinking contributes both favourably and adversely to
      health in the Western populations, but its effects on overall and cause-specific
      mortality in China are still poorly understood. METHODS: A nationally
      representative prospective cohort study included 220,000 men aged 40-79 years
      from 45 areas in China in 1990-91, and >40,000 deaths occurred during 15 years of
      follow-up. Cox regression was used to relate alcohol drinking to overall and
      cause-specific mortality, adjusting for age, area, smoking and education.
      RESULTS: Overall, 33% of the participants reported drinking alcohol regularly at
      baseline, consuming mainly distilled spirits, with an estimated mean amount
      consumed of 372 g/week (46.5 units per week). After excluding all men with prior
      disease at baseline and the first 3 years of follow-up, there was a 5% [95%
      confidence interval (CI) 2-8] excess risk of overall mortality among regular
      drinkers. Compared with non-drinkers, the adjusted hazard ratios among men who
      drank <140, 140-279, 280-419, 420-699 and >= 700 g/week were 0.97, 1.00, 1.02,
      1.12 and 1.27, respectively (P < 0.0001 for trend). The strength of the
      relationship appeared to be greater in smokers than in non-smokers. There was a
      strong positive association of alcohol drinking with mortality from stroke,
      oesophageal cancer, liver cirrhosis or accidental causes, a weak J-shaped
      association with mortality from ischaemic heart disease, stomach cancer and lung
      cancer and no apparent relationship with respiratory disease mortality.
      CONCLUSION: Among Chinese men aged 40-79 years, regular alcohol drinking was
      associated with a small but definite excess risk of overall mortality, especially
      among smokers.

PMID- 22596930
TI  - Commentary: Lifestyle factors and colorectal cancer microsatellite instability-
      molecular pathological epidemiology science, based on unique tumour principle.

PMID- 22596932
TI  - Commentary: thoughts on assessing evidence for gene by environment interaction.

PMID- 22596931
TI  - Recommendations and proposed guidelines for assessing the cumulative evidence on
      joint effects of genes and environments on cancer occurrence in humans.
AB  - We propose guidelines to evaluate the cumulative evidence of gene-environment (G
      * E) interactions in the causation of human cancer. Our approach has its roots in
      the HuGENet and IARC Monographs evaluation processes for genetic and
      environmental risk factors, respectively, and can be applied to common chronic
      diseases other than cancer. We first review issues of definitions of G * E
      interactions, discovery and modelling methods for G * E interactions, and issues
      in systematic reviews of evidence for G * E interactions, since these form the
      foundation for appraising the credibility of evidence in this contentious field.
      We then propose guidelines that include four steps: (i) score the strength of the
      evidence for main effects of the (a) environmental exposure and (b) genetic
      variant; (ii) establish a prior score category and decide on the pattern of
      interaction to be expected; (iii) score the strength of the evidence for
      interaction between the environmental exposure and the genetic variant; and (iv)
      examine the overall plausibility of interaction by combining the prior score and
      the strength of the evidence and interpret results. We finally apply the scheme
      to the interaction between NAT2 polymorphism and tobacco smoking in determining
      bladder cancer risk.

PMID- 22596933
TI  - Commentary: reporting and assessing evidence for interaction: why, when and how?

PMID- 22597352
TI  - Can Twitter predict disease outbreaks?

PMID- 22597353
TI  - The scatter of research: cross sectional comparison of randomised trials and
      systematic reviews across specialties.
AB  - OBJECTIVE: To estimate the degree of scatter of reports of randomised trials and
      systematic reviews, and how the scatter differs among medical specialties and
      subspecialties. DESIGN: Cross sectional analysis. DATA SOURCE: PubMed for all
      disease relevant randomised trials and systematic reviews published in 2009.
      STUDY SELECTION: Randomised trials and systematic reviews of the nine diseases or
      disorders with the highest burden of disease, and the broader category of disease
      to which each belonged. RESULTS: The scatter across journals varied considerably
      among specialties and subspecialties: otolaryngology had the least scatter (363
      trials across 167 journals) and neurology the most (2770 trials across 896
      journals). In only three subspecialties (lung cancer, chronic obstructive
      pulmonary disease, hearing loss) were 10 or fewer journals needed to locate 50%
      of trials. The scatter was less for systematic reviews: hearing loss had the
      least scatter (10 reviews across nine journals) and cancer the most (670 reviews
      across 279 journals). For some specialties and subspecialties the papers were
      concentrated in specialty journals; whereas for others, few of the top 10
      journals were a specialty journal for that area. Generally, little overlap
      occurred between the top 10 journals publishing trials and those publishing
      systematic reviews. The number of journals required to find all trials or reviews
      was highly correlated (r = 0.97) with the number of papers for each
      specialty/subspecialty. CONCLUSIONS: Publication rates of speciality relevant
      trials vary widely, from one to seven trials per day, and are scattered across
      hundreds of general and specialty journals. Although systematic reviews reduce
      the extent of scatter, they are still widely scattered and mostly in different
      journals to those of randomised trials. Personal subscriptions to journals, which
      are insufficient for keeping up to date with knowledge, need to be supplemented
      by other methods such as journal scanning services or systems that cover
      sufficient journals and filter articles for quality and relevance. Few current
      systems seem adequate.

PMID- 22597354
TI  - India's parliamentary panel sees nexus between drug regulators, manufacturers,
      and doctors.

PMID- 22597355
TI  - Euro MPs refuse to approve medicines agency's accounts until they tighten rules
      on conflicts of interest.

PMID- 22597533
TI  - Critical role of Egr transcription factors in regulating insulin biosynthesis,
      blood glucose homeostasis, and islet size.
AB  - Expression of early growth response protein (Egr)-1, a protein of the Egr family
      of zinc finger transcription factors, is stimulated in glucose-treated pancreatic
      beta-cells and insulinoma cells. The purpose of this study was to elucidate the
      role of Egr transcription factors in pancreatic beta-cells in vivo. To overcome
      the problem associated with redundancy of functions between Egr proteins,
      conditional transgenic mice were generated expressing a dominant-negative mutant
      of Egr-1 in pancreatic beta-cells. The Egr-1 mutant interferes with DNA binding
      of all Egr proteins and thus impairs the biological functions of the entire Egr
      family. Expression of the Egr-1 mutant reduced expression of TGFbeta and basic
      fibroblast growth factor, known target genes of Egr-1, whereas the expression of
      Egr-1, Egr-3, Ets-like gene-1 (Elk-1), and specificity protein-3 was not changed
      in the presence of the Egr-1 mutant. Expression of the homeobox protein pancreas
      duodenum homeobox-1, a major regulator of insulin biosynthesis, was reduced in
      islets expressing the Egr-1 mutant. Accordingly, insulin mRNA and protein levels
      were reduced by 75 or 25%, respectively, whereas expression of glucagon and
      somatostatin was not altered after expression of the Egr-1 mutant in beta-cells.
      Glucose tolerance tests revealed that transgenic mice expressing the Egr-1 mutant
      in pancreatic beta-cells displayed impaired glucose tolerance. In addition,
      increased caspase-3/7 activity was detected as a result of transgene expression,
      leading to a 20% decrease of the size of the islets. These results show that Egr
      proteins play an important role in controlling insulin biosynthesis, glucose
      homeostasis, and islet size of pancreatic beta-cells in vivo.

PMID- 22597534
TI  - Dihydrotestosterone inhibits lectin-like oxidized-LDL receptor-1 expression in
      aortic endothelial cells via a NF-kappaB/AP-1-mediated mechanism.
AB  - The mechanisms involved in the antiatherosclerotic effects of androgens are
      unclear. Although lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1)
      in endothelial cells plays critical roles in atherosclerosis, the effects of
      androgens on endothelial LOX-1 expression has not been examined. Therefore, to
      investigate the effects of dihydrotestosterone (DHT) on LOX-1 expression in
      rabbit aortic endothelial cells and cultured human aortic endothelial cells
      (HAEC), pellets containing DHT or placebo were s.c. implanted into 26 male New
      Zealand white rabbits at the time of castration or sham operation. The rabbits
      were then fed a high-cholesterol diet (HCD) for 2 wk. Microscopic examination of
      the aortic arch revealed that DHT significantly reduced HCD-induced LOX-1
      expression in endothelial cells compared with placebo. In cultured HAEC, DHT at
      concentrations above 10(-9) to 10(-7) mol/liter inhibited TNFalpha-induced LOX-1
      mRNA and protein expression. Deletion and mutation analysis of human LOX-1
      promoter-luciferase constructs transfected into HAEC with an androgen receptor
      (AR) expression plasmid revealed that the 12-O-tetradecanoylphorbol-13-acetate
      (TPA) response element (TRE; nucleotides -60/-53) contributed to the inhibitory
      effects of DHT on TNFalpha-induced LOX-1 expression. Chromatin
      immunoprecipitation (ChIP) and re-ChIP assays revealed that TNFalpha- and TPA
      dependent enrichment of p65 and phosphorylated c-Jun in the TRE chromatin region
      was inhibited by DHT-AR. Consistent with these results, DHT also suppressed TPA
      induced expression of LOX-1. In conclusion, DHT exerts antiatherosclerotic
      effects by suppressing endothelial LOX-1 expression. This effect is partly
      mediated by the suppression of nuclear factor-kappaB- and activator protein 1
      dependent activation of the LOX-1 promoter.

PMID- 22597535
TI  - Antiaging gene Klotho enhances glucose-induced insulin secretion by up-regulating
      plasma membrane levels of TRPV2 in MIN6 beta-cells.
AB  - Klotho is a recently discovered antiaging gene. Klotho is expressed in mouse
      pancreatic islets and in insulinoma beta-cells (MIN6 beta-cells). The purpose of
      this study was to investigate whether Klotho plays a role in the regulation of
      insulin secretion in MIN6 beta-cells by overexpression and silencing of Klotho.
      It is interesting that overexpression of Klotho increased glucose-induced insulin
      secretion in MIN6 beta-cells. Overexpression of mouse Klotho protein also
      significantly increased plasma membrane levels of transient receptor potential V2
      (TRPV2), calcium entry, and the glucose-induced increase in intracellular
      calcium. On the other hand, knockdown of Klotho by siRNA significantly decreased
      plasma membrane levels of TRPV2 and attenuated glucose-induced calcium entry and
      insulin secretion. Tranilast, a selective inhibitor of TRPV2, abolished the
      promoting effects of overexpression of Klotho on glucose-induced calcium entry
      and insulin secretion in MIN6 cells. Thus, TRPV2 lies in the downstream of Klotho
      in the regulation of glucose-induced insulin secretion. This study demonstrated,
      for the first time, that Klotho may enhance glucose-induced insulin secretion by
      up-regulating plasma membrane levels of TRPV2 and thus glucose-induced calcium
      responses. These findings reveal a previously unidentified role of Klotho in the
      regulation of glucose-induced insulin secretion in MIN6 beta-cells.

PMID- 22597536
TI  - Long terminal repeats act as androgen-responsive enhancers for the PSA-kallikrein
      locus.
AB  - The androgen receptor (AR) signaling pathway is a common therapeutic target for
      prostate cancer, because it is critical for the survival of both hormone
      responsive and castrate-resistant tumor cells. Most of the detailed understanding
      that we have of AR transcriptional activation has been gained by studying
      classical target genes. For more than two decades, Kallikrein 3 (KLK3) (prostate
      specific antigen) has been used as a prototypical AR target gene, because it is
      highly androgen responsive in prostate cancer cells. Three regions upstream of
      the KLK3 gene, including the distal enhancer, are known to contain consensus
      androgen-responsive elements required for AR-mediated transcriptional activation.
      Here, we show that KLK3 is one of a specific cluster of androgen-regulated genes
      at the centromeric end of the kallikrein locus with enhancers that evolved from
      the long terminal repeat (LTR) (LTR40a) of an endogenous retrovirus. Ligand
      dependent recruitment of the AR to individual LTR-derived enhancers results in
      concurrent up-regulation of endogenous KLK2, KLK3, and KLKP1 expression in LNCaP
      prostate cancer cells. At the molecular level, a kallikrein-specific duplication
      within the LTR is required for maximal androgen responsiveness. Therefore, KLK3
      represents a subset of target genes regulated by repetitive elements but is not
      typical of the whole spectrum of androgen-responsive transcripts. These data
      provide a novel and more detailed understanding of AR transcriptional activation
      and emphasize the importance of repetitive elements as functional regulatory
      units.

PMID- 22597574
TI  - Surgical treatment of laryngeal papillomatosis using narrow band imaging.
AB  - Laryngeal papillomatosis has a high rate of recurrence after surgery. Narrow band
      imaging (NBI) is a novel optical enhancement technology used for the diagnosis.
      This is the first report to date to indicate the availability of the combination
      of laryngomicro surgery and videoendoscopic surgery for laryngeal papillomatosis
      using NBI technology. The patients were a 34-year-old man and a 30-year-old man.
      Both patients underwent surgery in another hospital. However, due to recurrence,
      they were subsequently referred to the authors' department for further
      evaluation. The presence of papillomas was confirmed by NBI, and the papillomas
      were removed using an XPS Micro Debrider and a CO2 laser. Using the NBI system,
      the border between the normal mucosa and the papillomas could be clearly
      identified, allowing precise resection. Further treatment on the lesions has been
      carried out several times to date using NBI. The lesions have now been eradicated
      without further recurrence.

PMID- 22597575
TI  - Culture of human septal chondrocytes in a rotary bioreactor.
AB  - OBJECTIVES: (1) To show that extracellular matrix deposition in 3-dimensional
      culture of human septal chondrocytes cultured in a rotary bioreactor is
      comparable to the deposition achieved under static culture conditions. (2) To
      demonstrate that the biomechanical properties of human septal chondrocytes
      cultured in a bioreactor are enhanced with time and are analogous to beads
      cultured under static culture. STUDY DESIGN: Prospective, basic science. SETTING:
      Research laboratory. METHODS: Human septal chondrocytes from 9 donors were
      expanded in monolayer and seeded in alginate beads. The beads were cultured in a
      rotary bioreactor for 21 days in media supplemented with growth factors and human
      serum, using static culture as the control. Biochemical and biomechanical
      properties of the beads were measured. RESULTS: Glycosaminoglycan (GAG)
      accumulation significantly increased during 2 measured time intervals, 0 to 21
      days and 10 to 21 days (P < .01). No significant difference was seen between the
      static and bioreactor conditions. Substantial type II collagen production was
      demonstrated in the beads terminated at day 21 of culture in both conditions. In
      addition, the biomechanical properties of the beads were significantly improved
      at 21 days in comparison to beads from day 0. CONCLUSION: Human septal
      chondrocytes cultured in alginate beads exhibit significant matrix deposition and
      improved biomechanical properties after 21 days. Alginate bead diameter and
      stiffness positively correlated with GAG and type II collagen accretion. Matrix
      production in beads is supported by the use of a rotary bioreactor.

PMID- 22597576
TI  - Molecular basis of tobacco-induced bacterial biofilms: an in vitro study.
AB  - OBJECTIVE: To evaluate changes in the expression of biofilm-related genes when
      exposed to tobacco smoke and oxidative stress. STUDY DESIGN: Experimental, in
      vitro. Setting Laboratories of Rhinology and Microbiology, University of
      Pennsylvania. SUBJECTS AND METHODS: Bacterial biofilm mass was measured using
      crystal violet staining and measurement of the optical density. Biofilm-related
      genes of the Pseudomonas aeruginosa PAO1 strain (pilF, flgK, lasI, lasB, rhlA,
      and algC) were studied following repetitive exposure to exogenous tobacco smoke
      and hydrogen peroxide. This was done using a reporter plasmid. RESULTS: After 1
      exposure to smoke, there was no change in biofilm formation. However, after 2 and
      3 exposures, the biofilm formed had an increased mass (P < .05). With respect to
      oxidative stress in the form of H(2)O(2), bacterial cultures demonstrated a dose-
      and time-dependent induction of biofilm formation compared with control
      conditions. Gene expression following repetitive smoke exposure demonstrated an
      increase in expression of pilF, flgK, algC, and lasI genes (P < .05); a decrease
      in rhlA (P < .05); and no significant change in the lasB gene (P = 0.1). Gene
      expression following H(2)O(2) exposure demonstrated an increase in pilF (P <
      .05), whereas the other genes failed to demonstrate a statistical change.
      CONCLUSIONS: Repetitive tobacco smoke exposure leads to molecular changes in
      biofilm-related genes, and exposure to oxidative stress in the form of H(2)O(2)
      induces biofilm growth in PAO1. This could represent adaptative changes due to
      oxidative stress or chemically mediated through any of the several chemicals
      encountered in tobacco smoke and may explain increased biofilm formation in
      microbes isolated from smokers.

PMID- 22597577
TI  - How good is Google? The quality of otolaryngology information on the internet.
AB  - OBJECTIVE: To assess the quality of the information a patient (parent) may
      encounter using a Google search for typical otolaryngology ailments. STUDY
      DESIGN: Cross-sectional study. SETTING: Tertiary care center. METHODS: A Google
      keyword search was performed for 10 common otolaryngology problems including ear
      infection, hearing loss, tonsillitis, and so on. The top 10 search results for
      each were critically examined using the 16-item (1-5 scale) standardized DISCERN
      instrument. The DISCERN instrument was developed to assess the quality and
      comprehensiveness of patient treatment choice literature. RESULTS: A total of 100
      Web sites were assessed. Of these, 19 (19%) were primarily advertisements for
      products and were excluded from DISCERN scoring. Searches for more typically
      chronic otolaryngic problems (eg, tinnitus, sleep apnea, etc) resulted in more
      biased, advertisement-type results than those for typically acute problems (eg,
      ear infection, sinus infection, P = .03). The search for "sleep apnea treatment"
      produced the highest scoring results (mean overall DISCERN score = 3.49, range =
      1.81-4.56), and the search for "hoarseness treatment" produced the lowest scores
      (mean = 2.49, range = 1.56-3.56). Results from major comprehensive Web sites
      (WebMD, EMedicinehealth.com, Wikipedia, etc.) scored higher than other Web sites
      (mean DISCERN score = 3.46 vs 2.48, P < .001). CONCLUSION: There is marked
      variability in the quality of Web site information for the treatment of common
      otolaryngologic problems. Searches on more chronic problems resulted in a higher
      proportion of biased advertisement Web sites. Larger, comprehensive Web sites
      generally provided better information but were less than perfect in presenting
      complete information on treatment options.

PMID- 22597579
TI  - Preservation of viscoelastic properties of rabbit vocal folds after implantation
      of hyaluronic Acid-based biomaterials.
AB  - OBJECTIVES: To compare the rheological characteristics of structurally different
      hyaluronic acid (HA)-based biomaterials that are presently used for phonosurgery
      and to investigate their influence on the viscoelastic properties of vocal folds
      after implantation in an in vivo rabbit model. STUDY DESIGN: In vitro and in vivo
      rheometric investigation. SETTING: Experimental laboratory, Inha and Seoul
      National Universities. METHODS: Viscoelastic shear properties of 3 HA-based
      biomaterials (Rofilan, Restylane, and Reviderm) were measured with a strain
      controlled rheometer. These biomaterials were injected into the deep layers of
      rabbit vocal folds, and viscoelastic moduli of the injected vocal folds were
      determined 2 months after the injection. The vocal fold specimens were observed
      using a light microscope and a transmission electron microscope. RESULTS: All HA
      based biomaterials showed similar levels of shear viscosity, which were slightly
      higher than that of human vocal folds reported in previous studies. Compared with
      noninjected control vocal folds, there were no significant differences in the
      magnitudes of both elastic shear modulus (G') and viscous modulus (G") of
      injected vocal folds among all of the materials. Light microscopic images showed
      that all materials were observed in the deep layers of vocal folds and electron
      scanning images revealed that injected HA particles were homogeneously
      distributed in regions of collagenous fibers. CONCLUSION: HA-based biomaterials
      could preserve the viscoelastic properties of the vocal folds, when they were
      injected into vocal folds in an in vivo rabbit model. However, further studies on
      the influence of the biomaterials on the viscoelasticity of human vocal folds in
      ECM surroundings are still needed.

PMID- 22597578
TI  - Audiovestibular dysfunction associated with adoptive cell immunotherapy for
      melanoma.
AB  - OBJECTIVE: To understand the audiologic and vestibular toxicities associated with
      adoptive cell immunotherapy (ACI) targeting pigment-pathway antigens on melanoma
      and to investigate the use of intratympanic steroid injections in the treatment
      of these toxicities. STUDY DESIGN: Prospective nonrandomized study. SETTING:
      Tertiary clinical research center. METHODS: Thirty-two patients with progressive
      metastatic melanoma who failed conventional therapy underwent ACI with T cells
      genetically modified to target MART-1 (n = 18) or gp100 (n = 14). All patients
      received serial audiometric testing. Vestibular testing was performed on patients
      with vestibular complaints. Patients with significant deficits received
      intratympanic steroid injections. RESULTS: Of 32 patients, 15 had no hearing
      change, 9 had mild hearing loss, and 8 had moderate hearing loss following
      treatment. Ten patients received intratympanic steroid injections for mild (n =
      2) or moderate (n = 7) hearing loss or for significant imbalance (n = 1). Of
      those with mild hearing loss (n = 9), all but 1 recovered to pretreatment hearing
      levels. Four of 8 patients with moderate hearing loss recovered to baseline
      hearing levels, and 4 had partial recovery. All 7 patients with posttreatment
      vestibular complaints had demonstrable vestibular dysfunction. Three of these
      patients demonstrated recovery to normal vestibular function. The number of
      modified T cells infused for therapy correlated with the degree of
      audiovestibular deficit. CONCLUSION: Adoptive cell immunotherapy targeting
      pigment-pathway cell proteins, a novel therapy for melanoma, can induce hearing
      loss and vestibular dysfunction. The presumed mechanism of autoimmune attack on
      normal melanocytes in the cochlear stria vascularis and in the vestibular organs
      demonstrates the importance of melanocytes in normal inner ear function.

PMID- 22597705
TI  - Feasibility of evaluating quality cancer care using registry data and electronic
      health records: a population-based study.
AB  - OBJECTIVE: To evaluate the quality of patients care, a set of indicators of the
      standards of cancer care were defined. DESIGN:  SETTING:  PARTICIPANTS: We
      developed a set of indicators to assess the implementation in daily practice of
      recommendation produced by a regional network (Istituto Toscano Tumori). This set
      was tested in a retrospective study in the resident population of the Tuscany
      Region; the regional health system is organized on 12 local health authorities
      which refer to three macro areas (Area Vasta). The study included incident
      colorectal, lung and breast cancer cases listed in 2004 for the Tuscan Cancer
      Registry, a population-based registry which collected tumor cases diagnosed in
      all residents in Tuscany. Electronic data from registry database were used to
      determine the compliance with each indicator for patients in 2004. To validate
      the results, an ad hoc clinical survey including the same geographical area for
      the year 2006 was performed. INTERVENTION: None. MAIN OUTCOME MEASURES: The
      proportion of patients who fulfilled each of the indicators. RESULTS: Our study
      showed the feasibility of the evaluation of the quality of cancer care using
      cancer registry population-based data and major computerized information systems.
      The estimation of the selected indicators confirmed a good homogeneity among
      areas, and globally revealed a good intraregional performance. CONCLUSIONS:
      Further work is needed to develop specific quality measures, particularly about
      structural data and to continually revise indicators of quality of care. Data
      from a cancer registry, however, can be useful to evaluate quality of cancer
      care.

PMID- 22597706
TI  - Standard admission orders can improve the management of acute myocardial
      infarction.
AB  - OBJECTIVE: To evaluate whether the use of standard admission orders for patients
      admitted with acute myocardial infarction (AMI) is associated with better
      hospital quality of care. DESIGN: Secondary analysis of a population-based
      database derived from a large cluster randomized AMI quality improvement trial.
      SETTING: Seventy-eight acute care hospital corporations located in Ontario,
      Canada. PARTICIPANTS: A total of 5338 patients with AMI admitted directly to the
      coronary care/intensive care units of participating hospitals in 2004/2005. Main
      outcome measure(s) Hospital performance on seven process-of-care measures and a
      combined composite process-of-care measure. Secondary outcomes were 30-day and 1
      year mortality rates. RESULTS: Most patients (81%) were treated with standard
      admission orders. These patients were more likely to receive four of seven
      identified process-of-care measures (P< 0.05), including fibrinolytics <= 30 min
      or primary percutaneous coronary intervention <= 90 min of arrival, fibrinolytics
      administration decided by emergency department physician, aspirin <= 6 h of
      arrival and lipid test <= 24 h. After propensity-score matching (for risk
      adjustment), use of standard admission orders was not associated with
      significantly lower 30-day or 1-year mortality. However, patients who met the
      composite process-of-care measure had lower 30-day and 1-year mortality (relative
      risk= 0.51 (95% confidence interval (CI): 0.40-0.67) and 0.70 (95% CI: 0.58
      0.84), respectively). CONCLUSION: In AMI, the use of standard admission orders
      was associated with improved hospital performance on several but not all acute
      process-of-care quality indicators. The utilization of standard admission orders
      should be considered as a strategy for improving hospital care in patients
      admitted with AMI.

PMID- 22597759
TI  - Syrian doctors tell charity that "being caught with patients is like being caught
      with a weapon".

PMID- 22598484
TI  - Phospholipid scramblase expression in the pregnant mouse uterus in LPS-induced
      preterm delivery.
AB  - Phospholipid scramblases (PLSCR), stimulated by proinflammatory cytokines, are
      thought to mediate the loss of lipid asymmetry in cell membranes, allowing for
      specific reactions in the coagulation cascade. The PLSCR may therefore provide a
      link between inflammation, coagulation, and, because thrombin is a uterotonic,
      preterm birth (PTB). To explore the relationship between PLSCR expression and
      inflammation-related PTB, we utilized reverse transcriptase-polymerase chain
      reaction and Western blot studies to quantify messenger RNA (mRNA) and protein
      expression for the 4 PLSCR homologues (PLSCR 1-4). Uteri from day 15 pregnant
      mice were harvested at several time points after intrauterine lipopolysaccharide
      (LPS) injection (or normal saline, for controls). Expression of mRNA in all 4
      Plscr isoforms was demonstrated. Lipopolysaccharide treatment resulted in
      increased expression of PLSCR-1 and a decrease in Plscr4 mRNA, thereby
      demonstrating modulation of PLSCR-1 and PLSCR-4 in LPS-induced PTB. Additionally,
      protein expression was confirmed for all except PLSCR-4, with increased
      expression of PLSCR-1 after LPS treatment.

PMID- 22598485
TI  - Intra-amniotic administration of E coli lipopolysaccharides causes sustained
      inflammation of the fetal skin in sheep.
AB  - Preterm birth is associated with in utero infection and inflammation. Although
      the fetal membranes and fetus contribute to the intra-amniotic inflammatory
      profile, the relationships between a proinflammatory exposure to the fetal
      compartment and cytokine expression in the fetal skin are unknown. Using an ovine
      model, we asked whether the fetal skin would generate an extended response to
      inflammatory stimuli. Relative to control, intra-amniotic lipopolysaccharide
      (LPS) induced significant increases in cytokine/chemokine (interleukin 1beta, IL
      8, tumor necrosis factor-alpha, and monocyte chemoattractant protein 1)
      expression in skin that lasted for at least 15 days. Histological analysis
      demonstrated inflammatory cell infiltration in skin between 2 days and 15 days
      post-LPS exposure. In contrast to the fetal lung, the fetal skin continues to
      express proinflammatory cytokines for at least 15 days after exposure to LPS.
      These novel data suggest that the fetal skin may cause prolonged in utero
      inflammatory response causally associated with preterm birth.

PMID- 22598486
TI  - Plasma hemopexin as a potential regulator of vascular responsiveness to
      angiotensin II.
AB  - This brief review focuses on the functional activities of plasma hemopexin
      recently recognized by several authors. In particular, the protease-like activity
      of hemopexin in vitro is linked with downregulation of the vascular angiotensin
      II receptor in vivo, leading to vascular expansion. Also a potential mechanism of
      inhibition of hemopexin activity by extracellular adenosine triphosphate is
      considered.

PMID- 22599322
TI  - A spatial bivariate probit model for correlated binary data with application to
      adverse birth outcomes.
AB  - Motivated by a study examining geographic variation in birth outcomes, we develop
      a spatial bivariate probit model for the joint analysis of preterm birth and low
      birth weight. The model uses a hierarchical structure to incorporate individual
      and areal-level information, as well as spatially dependent random effects for
      each spatial unit. Because rates of preterm birth and low birth weight are likely
      to be correlated within geographic regions, we model the spatial random effects
      via a bivariate conditionally autoregressive prior, which induces regional
      dependence between the outcomes and provides spatial smoothing and sharing of
      information across neighboring areas. Under this general framework, one can
      obtain region-specific joint, conditional, and marginal inferences of interest.
      We adopt a Bayesian modeling approach and develop a practical Markov chain Monte
      Carlo computational algorithm that relies primarily on easily sampled Gibbs
      steps. We illustrate the model using data from the 2007-2008 North Carolina
      Detailed Birth Record. 

PMID- 22599356
TI  - Targeted hypoglossal neurostimulation for obstructive sleep apnoea: a 1-year
      pilot study.
AB  - Continuous positive airway pressure (CPAP) is an effective but cumbersome
      treatment for obstructive sleep apnoea (OSA). Noncompliant patients need
      alternative therapies. We studied a tongue neurostimulation approach: targeted
      hypoglossal neurostimulation (THN) therapy with the aura6000TM System. A multi
      contact electrode positioned around the main trunk of the twelfth nerve connected
      to an implanted pulse generator stimulates segments of the nerve, activating
      dilator muscles. The primary objective was to improve the polysomnographically
      determined apnoea/hypopnoea index (AHI) at 3 months, and maintain the improvement
      after 12 months of treatment. 13 out of 14 operated patients were successfully
      implanted. At 12 months, the AHI decreased from 45+/-18 to 21+/-17, a 53%
      reduction (p<0.001). The 4% oxygen desaturation index fell from 29+/-20 to 15+/
      16 and the arousal index from 37+/-13 to 25+/-14, both p<0.001. The Epworth
      sleepiness scale decreased from 11+/-7 to 8+/-4 (p=0.09). THN was neither painful
      nor awakened patients, who all complied with therapy. There were two transient
      tongue paresis. The present study represents the longest study of any hypoglossal
      neurostimulation reported to date. We conclude that THN is safe and effective to
      treat OSA in patients not compliant with CPAP.

PMID- 22599357
TI  - Bronchoalveolar lavage neuregulin-1 is elevated in acute lung injury and
      correlates with inflammation.
AB  - Shedding of neuregulin (NRG)-1 from the pulmonary epithelium leads to activation
      of the epithelial human epidermal growth factor receptor (HER)2 receptor,
      increased pulmonary epithelial permeability and acute lung injury (ALI). We
      sought to determine whether NRG-1 was detectable and elevated in bronchoalveolar
      lavage (BAL) and plasma from patients with ALI compared with controls and to
      determine whether a correlation exists between NRG-1 and inflammation and outcome
      in ALI. Matched BAL and plasma samples were obtained from 23 ALI patients
      requiring intubation and mechanical ventilation. Control patients (n=5) included
      healthy volunteers. NRG-1 and indices of inflammation were measured in BAL and
      plasma via ELISA. The mean+/-sd BAL NRG-1 concentration in ALI patients was
      187.0+/-21.35 pg.mL(-1) compared with 85.50+/-9.2 pg.mL(-1) in controls
      (p=0.001). Increased BAL NRG-1 was associated with markers of inflammation, and
      inversely correlated with ventilator-free days (VFDs; r= -0.51, p=0.015). Plasma
      NRG-1 was elevated in ALI patients compared with controls (611.7+/-354.2 versus
      25.17+/-19.33 pg.mL(-1), p<0.001) and inversely correlated with VFDs (r= -0.51,
      p=0.04). These results confirm shedding of NRG-1 in ALI and suggest that the NRG
      1-HER2 pathway is active in patients with ALI.

PMID- 22599358
TI  - Evaluation of upper airway patency during Cheyne-Stokes breathing in heart
      failure patients.
AB  - Little is known about the changes in upper airway calibre in Cheyne-Stokes
      respiration (CSR) during sleep in patients with congestive heart failure. This
      study aimed to test the hypothesis that upper airway closure occurs during
      central CSR events, by assessing upper airway calibre during sleep using the
      forced oscillation technique (FOT). Nine males with compensated heart failure
      (left ventricular ejection fraction mean +/- sem 27.9 +/- 5.1%) and predominant
      central CSR (apnoea/hypopnoea index 43.9 +/- 4.2 events . h(-1)) were studied
      during overnight polysomnography, which included pneumotachography, inductance
      plethysmography or oesophageal pressure and FOT-derived impedance signal (|Z|).
      Baseline |Z| values during stable breathing in stage 2 sleep were 11.0 +/- 1.3
      cmH(2)O . s . L(-1). Mean |Z| increased to 31.9 +/- 6.7 cmH(2)O . s . L(-1)
      during obstructive apnoeas (7% of events, n = 46). Increases in |Z| consistent
      with upper airway narrowing (more than two-fold baseline) were common during
      central apnoeas (50 +/- 12% of events) occurring in the middle or end of apnoeas
      and occurred during some central hypopnoeas (16 +/- 10% of events), typically in
      the expiratory phase. These findings indicate that in heart failure patients,
      reductions in upper airway calibre are common during CSR apnoeas, and may also
      occur during central hypopnoeas.

PMID- 22599359
TI  - Clinical characteristics and corticosteroid treatment of acute eosinophilic
      pneumonia.
AB  - The clinical characteristics and optimal duration of corticosteroid treatment for
      acute eosinophilic pneumonia (AEP) have not been fully evaluated. This was a
      retrospective study of prospectively collected data from 137 patients with AEP,
      treated with standardised protocol, to clarify the clinical characteristics and
      compare the efficacies of 2 weeks versus 4 weeks of corticosteroid treatment for
      AEP. The majority of the patients altered their smoking habits within a median
      (interquartile range) of 17 (13-26) days prior to development of AEP. 80 (58%)
      patients presented with acute respiratory failure. A total of 127 (92%) patients
      were treated with corticosteroids: 4 weeks, n=42; 2 weeks, n=85. Major symptoms
      were resolved in 3 days and the severity of respiratory failure was inversely
      correlated with clinical outcomes. After adjusting for differences in baseline
      characteristics between the groups, the differences in adjusted mean (95%
      confidence interval) for resolution of dyspnoea and disappearance of all symptoms
      were 0.57 (-0.71-1.86) and -0.04 (-1.91-1.83) days, respectively. The difference
      in adjusted proportion of resolution of radiological abnormalities was 6.92% (
      8.19-22.02). In conclusion, the duration of corticosteroid treatment could be
      shortened to 2 weeks, even in patients with respiratory failure.

PMID- 22599360
TI  - A new double-tracer gas single-breath washout to assess early cystic fibrosis
      lung disease.
AB  - In cystic fibrosis (CF), tests for ventilation inhomogeneity are sensitive but
      not established for clinical routine. We assessed feasibility of a new double
      tracer gas single-breath washout (SBW) in school-aged children with CF and
      control subjects, and compared SBW between groups and with multiple-breath
      nitrogen washout (MBNW). Three SBW and MBNW were performed in 118 children (66
      with CF) using a side-stream ultrasonic flowmeter setup. The double-tracer gas
      containing 5% sulfur hexafluoride and 26.3% helium was applied during one tidal
      breath. Outcomes were SBW phase III slope (SIII(DTG)), MBNW-derived lung
      clearance index (LCI), and indices of acinar (S(acin)) and conductive (S(cond))
      ventilation inhomogeneity. SBW took significantly less time to perform than MBNW.
      SBW and MBNW were feasible in 109 (92.4%) and 98 (83.0%) children, respectively.
      SIII(DTG) differed between children with CF and controls, mean+/-sd was -456.7+/
      492.8 and -88.4+/-129.1 mg.mol.L(-1), respectively. Abnormal SIII(DTG) was
      present in 36 (59%) children with CF. SIII(DTG) was associated with LCI (r= 
      0.58) and S(acin) (r= -0.58), but not with S(cond). In CF, steeply sloping
      SIII(DTG) potentially reflects ventilation inhomogeneity near the acinus
      entrance. This tidal SBW is a promising test to assess ventilation inhomogeneity
      in an easy and fast way.

PMID- 22599580
TI  - Transcorneal electrical stimulation promotes survival of photoreceptors and
      improves retinal function in rhodopsin P347L transgenic rabbits.
AB  - PURPOSE: To determine whether transcorneal electrical stimulation (TES) has
      neuroprotective effects on the photoreceptors, and whether it slows the rate of
      decrease of the electroretinogram (ERG) in rhodopsin P347L transgenic (Tg)
      rabbits. METHODS: Six-week-old Tg rabbits received TES through a contact lens
      electrode on the left eye weekly for 6 weeks. The right eyes received sham
      stimulation on the same days. Electroretinograms (ERGs) were recorded before and
      at 12 weeks after the TES. After the last ERG recordings, the animals were
      euthanized for morphologic analysis of the retinas. Immunohistochemical (IHC)
      analysis was performed to detect the immunostaining by peanut agglutinin (PNA)
      and rhodopsin antibodies in the retinas. RESULTS: The a- and b-wave amplitudes of
      the photopic ERGs and the b-wave amplitudes of the scotopic ERGs at higher
      stimulus intensities were significantly larger in the TES eyes than in the sham
      stimulated eyes (P<0.05, respectively). Morphologic analyses showed that the mean
      thickness of the outer nuclear layer (ONL) in the visual streak at 12 weeks was
      significantly thicker in TES eyes than in sham-stimulated eyes (P<0.05). IHC
      showed that the immunostaining by PNA and rhodopsin antibody in the TES-treated
      retinas was stronger than that in the sham-stimulated retinas. CONCLUSIONS: TES
      promotes the survival of photoreceptors and preserves the ERGs in Tg rabbits.
      Although further investigations are necessary before using TES on patients, these
      findings indicate that TES should be considered for therapeutic treatment for RP
      patients with a P347L mutation of rhodopsin.

PMID- 22599361
TI  - European COPD Audit: design, organisation of work and methodology.
AB  - Clinical audit has an important role as an indicator of the clinical practice in
      a given community. The European Respiratory Society (ERS) chronic obstructive
      pulmonary disease (COPD) audit was designed as a pilot study to evaluate clinical
      practice variability as well as clinical and organisational factors related to
      outcomes for COPD hospital admissions across Europe. The study was designed as a
      prospective observational noninterventional cohort trial, in which 422 hospitals
      from 13 European countries participated. There were two databases: one for
      hospital's resources and organisation and one for clinical information. The study
      was comprised of an initial 8-week phase during which all consecutive cases
      admitted to hospital due to an exacerbation of COPD were identified and
      information on clinical practice was gathered. During the 90-day second phase,
      mortality and readmissions were recorded. Patient data were anonymised and
      encrypted through a multi-lingual web-tool. As there is no pan-European Ethics
      Committee for audits, all partners accepted the general ethical rules of the ERS
      and ensured compliance with their own national ethical requirements. This paper
      describes the methodological issues encountered in organising and delivering a
      multi-national European audit, highlighting goals, barriers and achievements, and
      provides valuable information for those interested in developing clinical audits.

PMID- 22599581
TI  - The impact of visual and nonvisual factors on quality of life and adaptation in
      adults with visual impairment.
AB  - PURPOSE: Quality of life (QoL) questionnaires have been suggested as the most
      appropriate way to measure the effectiveness of low vision rehabilitation. This
      study investigated the relative contribution of visual and psychosocial factors
      to different aspects of QoL in people with low vision. METHODS: A total of 448
      consecutive patients between the ages of 18 and 96 years, with best-corrected
      binocular visual acuity<=6/18 and attending a low vision clinic, were recruited.
      Telephone delivery of previously validated questionnaires was used. The Low
      Vision Quality of Life (LVQOL), the Adaptation to Age-Related Vision Loss (AVL)
      12, and the Keele Participation Restriction Questionnaire (KAP) questionnaires
      were considered as outcome measures for functional vision, adaptation to vision
      loss, and participation restriction, respectively. Personality (BFI-10),
      religious beliefs (SBI-15), social support (MOS), the mental and physical
      components of general health (the MCS and PCS of SF-12), well-being (WHO-5), use
      of magnifiers (MLVQ), understanding of their eye condition and satisfaction with
      the eye clinic (MLVQ), level of education, and financial status were all
      considered as predictive of QoL. RESULTS: Regression analysis found the PCS and
      MCS from SF-12 to be major predictors of LVQOL, AVL-12, and KAP scores. Although
      distance visual acuity and contrast sensitivity were predictors of LVQOL scores,
      "use of magnifiers" did not contribute to any of the QoL measures. CONCLUSIONS:
      Nonvisual factors, such as physical and mental health, were found to be stronger
      predictors of QoL in people with low vision than visual factors such as contrast
      sensitivity and visual acuity, or the use of magnifiers. Researchers need to be
      aware when measuring QoL in a population with low vision that even vision-related
      QoL is strongly influenced by nonvisual variables.

PMID- 22599582
TI  - Microbead-induced ocular hypertensive mouse model for screening and testing of
      aqueous production suppressants for glaucoma.
AB  - PURPOSE: To characterize the microbead-induced ocular hypertension (OHT) mouse
      model and investigate its potential use for preclinical screening and evaluation
      of ocular hypotensive agents, we tested the model's responses to major
      antiglaucoma drugs. METHODS: Adult C57BL/6J mice were induced to develop OHT
      unilaterally by intracameral injection of microbeads. The effects of the most
      commonly used ocular hypotensive drugs, including timolol, brimonidine,
      brinzolamide, pilocarpine, and latanoprost, on IOP and glaucomatous neural damage
      were evaluated. Degeneration of retinal ganglion cells (RGCs) and optic nerve
      axons were quantitatively assessed using immunofluorescence labeling and
      histochemistry. Thickness of the ganglion cell complex (GCC) was also assessed
      with spectral-domain optical coherence tomography (SD-OCT). RESULTS: A microbead
      induced OHT model promptly responded to drugs, such as timolol, brimonidine, and
      brinzolamide, that lower IOP through suppressing aqueous humor production and
      showed improved RGC and axon survival as compared to vehicle controls.
      Accordingly, SD-OCT detected significantly less reduction of GCC thickness in
      mice treated with all three aqueous production suppressants as compared to the
      vehicle contol-treated group. In contrast, drugs that increase aqueous outflow,
      such as pilocarpine and latanoprost, failed to decrease IOP in the microbead
      induced OHT mice. CONCLUSIONS: Microbead-induced OHT mice carry dysfunctional
      aqueous outflow facility and therefore offer a unique model that allows selective
      screening of aqueous production suppressant antiglaucoma drugs or for studying
      the mechanisms regulating aqueous humor production. Our data set the stage for
      using GCC thickness assessed by SD-OCT as an imaging biomarker for noninvasive
      tracking of neuronal benefits of glaucoma therapy in this model.

PMID- 22599585
TI  - Smoking and risk of age-related cataract: a meta-analysis.
AB  - PURPOSE: We conducted a meta-analysis to evaluate the relationship between
      smoking and age-related cataract (ARC). METHODS: Eligible studies were identified
      via computer searches and reviewing the reference lists of the key articles. The
      summary relative risk ratio (RR) or odds ratio (OR) and 95% confidence interval
      (CI) were calculated. Study-specific risk estimates were pooled using a random
      effects model. Meta-regression to assess heterogeneity by several covariates and
      subgroup analysis on ARC types were performed. RESULTS: A total of 13 prospective
      cohort and eight case-control studies met our inclusion criteria. Ever smoking
      was statistically significantly associated with increased risk of ARC among
      cohort studies (OR 1.41, 95% CI 1.23-1.62) and case-control studies (OR 1.57, 95%
      CI 1.20-2.07). In subgroup analysis, ever smoking exhibited a positive
      relationship with nuclear cataract (NC; OR 1.66, 95% CI 1.46-1.89) and a
      marginally significant relationship with posterior subcapsular cataract (OR 1.43,
      95% CI 0.99-2.07) in cohort studies. Similar results were found in case-control
      studies (NC OR 1.86, 95% CI 1.47-2.36; posterior subcapsular cataract OR 1.60,
      95% CI 0.97-2.65). Current smokers were at higher risk of ARC than past smokers.
      No association between smoking and cortical cataract was observed. CONCLUSIONS:
      The overall current literature suggests that smoking was associated with
      increased risk of ARC, especially NC. Further efforts should be made to confirm
      these findings and clarify the underlying biological mechanisms.

PMID- 22599583
TI  - Redox proteomic identification of visual arrestin dimerization in photoreceptor
      degeneration after photic injury.
AB  - PURPOSE: Light-induced oxidative stress is an important risk factor for age
      related macular degeneration, but the downstream mediators of photoreceptor and
      retinal pigment epithelium cell death after photic injury are unknown. Given our
      previous identification of sulfhydryl/disulfide redox status as a factor in
      photoreceptor survival, we hypothesized that formation of one or more disulfide
      linked homo- or hetero-dimeric proteins might signal photoreceptor death after
      light-induced injury. METHODS: Two-dimensional (non-reducing/reducing) gel
      electrophoresis of Wistar rat retinal homogenates after 10 hours of 10,000 lux
      (4200 degrees K) light in vivo, followed by mass spectrometry identification of
      differentially oxidized proteins. RESULTS: The redox proteomic screen identified
      homodimers of visual arrestin (Arr1; S antigen) after toxic levels of light
      injury. Immunoblot analysis revealed a light duration-dependent formation of Arr1
      homodimers, as well as other Arr1 oligomers. Immunoprecipitation studies revealed
      that the dimerization of Arr1 due to photic injury was distinct from association
      with its physiological binding partners, rhodopsin and enolase1. Systemic
      delivery of tris(2-carboxyethyl)phosphine, a specific disulfide reductant, both
      decreased Arr1 dimer formation and protected photoreceptors from light-induced
      degeneration in vivo. CONCLUSIONS: These findings suggest a novel arrestin
      associated pathway by which oxidative stress could result in cell death, and
      identify disulfide-dependent dimerization as a potential therapeutic target in
      retinal degeneration.

PMID- 22599584
TI  - Automated quantification of volumetric optic disc swelling in papilledema using
      spectral-domain optical coherence tomography.
AB  - PURPOSE: To develop an automated method for the quantification of volumetric
      optic disc swelling in papilledema subjects using spectral-domain optical
      coherence tomography (SD-OCT) and to determine the extent that such volumetric
      measurements correlate with Frisen scale grades (from fundus photographs) and two
      dimensional (2-D) peripapillary retinal nerve fiber layer (RNFL) and total
      retinal (TR) thickness measurements from SD-OCT. METHODS: A custom image-analysis
      algorithm was developed to obtain peripapillary circular RNFL thickness, TR
      thickness, and TR volume measurements from SD-OCT volumes of subjects with
      papilledema. In addition, peripapillary RNFL thickness measures from the
      commercially available Zeiss SD-OCT machine were obtained. Expert Frisen scale
      grades were independently obtained from corresponding fundus photographs.
      RESULTS: In 71 SD-OCT scans, the mean (+/- standard deviation) resulting TR
      volumes for Frisen scale 0 to scale 4 were 11.36 +/- 0.56, 12.53 +/- 1.21, 14.42
      +/- 2.11, 17.48 +/- 2.63, and 21.81 +/- 3.16 mm(3), respectively. The Spearman's
      rank correlation coefficient was 0.737. Using 55 eyes with valid Zeiss RNFL
      measurements, Pearson's correlation coefficient (r) between the TR volume and the
      custom algorithm's TR thickness, the custom algorithm's RNFL thickness, and
      Zeiss' RNFL thickness was 0.980, 0.929, and 0.946, respectively. Between Zeiss'
      RNFL and the custom algorithm's RNFL, and the study's TR thickness, r was 0.901
      and 0.961, respectively. CONCLUSIONS: Volumetric measurements of the degree of
      disc swelling in subjects with papilledema can be obtained from SD-OCT volumes,
      with the mean volume appearing to be roughly linearly related to the Frisen scale
      grade. Using such an approach can provide a more continuous, objective, and
      robust means for assessing the degree of disc swelling compared with presently
      available approaches.

PMID- 22599586
TI  - Overexpression of human HMW FGF-2 but not LMW FGF-2 reduces the cytotoxic effect
      of lentiviral gene transfer in human corneal endothelial cells.
AB  - PURPOSE: Recently, insertion of immuno-modulatory or anti-apoptotic genes into
      corneal endothelial cells (HCECs) came into focus. Basic FGF-2 occurs in one
      secreted (low molecular weight, LMW, 18 kD) and four nuclear (high molecular
      weight, HMW, 22-34 kD) isoforms. HMW isoforms are known differentiation and
      survival factors, while LMW FGF-2 is a known mitogen. The effect of FGF-2
      overexpression of each of the five known isoforms on HCEC cell survival after
      lentiviral gene transfer in different culture media was investigated. METHODS:
      Cells were transduced with lentiviral vectors encoding for each of the five FGF-2
      isoforms. Transduction efficiency and expression of individual FGF-2 isoforms was
      assessed by marker gene transfer and western blotting. Primary HCECs were
      cultured and transduced in four different media previously described for HCEC
      cultivation or corneal organ cultivation. Cytotoxic effect of virus infection and
      a possible rescue effect of FGF-2 overexpression were determined by resazurin
      conversion assay. RESULTS: Transduction with FGF-2 encoding lentiviral vectors
      resulted in overexpression of the respective isoform in all tested cell
      populations. Western blotting after total cell lysis proved nuclear localization
      of transgenic HMW isoforms. Overexpression of HMW FGF-2-especially 34 kD FGF-2
      reduced lentiviral cytotoxicity, while overexpression of LMW FGF-2 aggravated
      viral cytotoxicity. CONCLUSIONS: Cytotoxicity of lentiviral gene transfer in
      corneal endothelial cells may be reduced by using bicistronic vectors that encode
      for the target gene and the 34-kD isoform of human FGF-2. Such cotransduction of
      a survival factor may increase cell survival after gene transfer, thereby
      improving gene therapeutic approaches.

PMID- 22599920
TI  - Five-item score for obstructed defecation syndrome: study of validation.
AB  - The use of a dedicated score represents an essential tool for the clinical
      staging of obstructed defecation syndrome (ODS), for subsequent diagnostic and
      therapeutic options, and for the evaluation of the results. This study was
      designed to develop and validate a new, simple, and disease-specific scoring
      system for ODS. The questionnaire consists of 5 items: excessive straining,
      incomplete rectal evacuation, use of enemas and/or laxatives, vaginal-anal
      perineal digitations, and abdominal discomfort and/or pain. Each item was graded
      from 0 to 5 with a score ranging from 0 (no symptoms) to 20 (very severe
      symptoms). A specific statistical analysis identifies the new score as a valuable
      and concise instrument, which demonstrates, overall, excellent concurrent
      validity, reproducibility, internal consistency, and discriminant validity for
      the diagnosis and grading of ODS. The use of this questionnaire may improve
      uniformity in clinical research and may allow a more precise evaluation of
      symptom severity and treatment effectiveness in ODS.

PMID- 22600024
TI  - Behcet's disease with superior vena cava syndrome related to pacemaker leads: a
      case report.

PMID- 22600358
TI  - This Week in JAMA.

PMID- 22600359
TI  - About This Journal.

PMID- 22600360
TI  - The Canal at Saint-MammesThe Canal at Saint-Mammes.

PMID- 22600362
TI  - The Other SideThe Other Side.

PMID- 22600361
TI  - SciaticaSciatica.

PMID- 22600364
TI  - New Tactics Help Curb Adolescent Substance Abuse and DependenceNew Tactics Help
      Curb Adolescent Substance Abuse and Dependence.

PMID- 22600363
TI  - Experts Look for Ways to Lessen Impact of Drug Shortages and
      DiscontinuationsExperts Look for Ways to Lessen Impact of Drug Shortages and
      Discontinuations.

PMID- 22600366
TI  - Kidney Disease Mystery Solved?Kidney Disease Mystery Solved?

PMID- 22600365
TI  - Preventing NeurodegenerationPreventing Neurodegeneration.

PMID- 22600368
TI  - Chagas Disease InitiativeChagas Disease Initiative.

PMID- 22600367
TI  - Screening Early EmbryosScreening Early Embryos.

PMID- 22600369
TI  - Symptomatic Early Neurosyphilis Among HIV-Positive Men Who Have Sex With Men-Four
      Cities, United States, January 2002-June 2004Symptomatic Early Neurosyphilis
      Among HIV-Positive Men Who Have Sex With Men-Four Cities, United States, January
      2002-June 2004.

PMID- 22600370
TI  - Advanced Pneumoconiosis Among Working Underground Coal Miners-Eastern Kentucky
      and Southwestern Virginia, 2006Advanced Pneumoconiosis Among Working Underground
      Coal Miners-Eastern Kentucky and Southwestern Virginia, 2006.

PMID- 22600371
TI  - Notice to Readers: Update on Supply of Vaccines Containing Varicella-Zoster
      VirusNotice to Readers: Update on Supply of Vaccines Containing Varicella-Zoster
      Virus.

PMID- 22600372
TI  - Predictive Index for Renal Replacement TherapyPredictive Index for Renal
      Replacement Therapy.

PMID- 22600373
TI  - Predictive Index for Renal Replacement Therapy-ReplyPredictive Index for Renal
      Replacement Therapy-Reply.

PMID- 22600374
TI  - Obesity and the Right BrainObesity and the Right Brain.

PMID- 22600375
TI  - Obesity and the Right Brain-ReplyObesity and the Right Brain-Reply.

PMID- 22600377
TI  - Access and Diversity in Academic Mentoring-ReplyAccess and Diversity in Academic
      Mentoring-Reply.

PMID- 22600376
TI  - Access and Diversity in Academic MentoringAccess and Diversity in Academic
      Mentoring.

PMID- 22600378
TI  - Cardiovascular Response to a Modern Roller Coaster RideCardiovascular Response to
      a Modern Roller Coaster Ride.

PMID- 22600380
TI  - Nutrition and Wound HealingNutrition and Wound Healing.

PMID- 22600379
TI  - Typographical Error in: A 59-Year-Old Man Considering Implantation of a Cardiac
      Defibrillator.

PMID- 22600382
TI  - The Science of Addiction: From Neurobiology to TreatmentThe Science of Addiction:
      From Neurobiology to Treatment.

PMID- 22600381
TI  - Patients With Substance Abuse Problems: Effective Identification, Diagnosis, and
      TreatmentPatients With Substance Abuse Problems: Effective Identification,
      Diagnosis, and Treatment.

PMID- 22600384
TI  - Power of Pills: Social, Ethical & Legal Issues in Drug Development, Marketing &
      PricingPower of Pills: Social, Ethical & Legal Issues in Drug Development,
      Marketing & Pricing.

PMID- 22600383
TI  - How Everyday Products Make People Sick: Toxins at Home and in the WorkplaceHow
      Everyday Products Make People Sick: Toxins at Home and in the Workplace.

PMID- 22600385
TI  - PSYCHIC CONTAGION OF CRIMINAL IMPULSE.PSYCHIC CONTAGION OF CRIMINAL IMPULSE.

PMID- 22600734
TI  - Rtips: fast and accurate tools for RNA 2D structure prediction using integer
      programming.
AB  - We present a web-based tool set Rtips for fast and accurate prediction of RNA 2D
      complex structures. Rtips comprises two computational tools based on integer
      programming, IPknot for predicting RNA secondary structures with pseudoknots and
      RactIP for predicting RNA-RNA interactions with kissing hairpins. Both servers
      can run much faster than existing services with the same purpose on large data
      sets as well as being at least comparable in prediction accuracy. The Rtips web
      server along with the stand-alone programs is freely accessible at
      http://rna.naist.jp/.

PMID- 22600735
TI  - ASEB: a web server for KAT-specific acetylation site prediction.
AB  - Protein lysine acetylation plays an important role in the normal functioning of
      cells, including gene expression regulation, protein stability and metabolism
      regulation. Although large amounts of lysine acetylation sites have been
      identified via large-scale mass spectrometry or traditional experimental methods,
      the lysine (K)-acetyl-transferase (KAT) responsible for the acetylation of a
      given protein or lysine site remains largely unknown due to the experimental
      limitations of KAT substrate identification. Hence, the in silico prediction of
      KAT-specific acetylation sites may provide direction for further experiments. In
      our previous study, we developed the acetylation set enrichment based (ASEB)
      computer program to predict which KAT-families are responsible for the
      acetylation of a given protein or lysine site. In this article, we provide KAT
      specific acetylation site prediction as a web service. This web server not only
      provides the online tool and R package for the method in our previous study, but
      several useful services are also included, such as the integration of protein
      protein interaction information to enhance prediction accuracy. This web server
      can be freely accessed at http://cmbi.bjmu.edu.cn/huac.

PMID- 22600736
TI  - Dynamic acetylation of lysine-4-trimethylated histone H3 and H3 variant biology
      in a simple multicellular eukaryote.
AB  - Dynamic acetylation of all lysine-4-trimethylated histone H3 is a complex
      phenomenon involved in Immediate-early gene induction in metazoan eukaryotes.
      Higher eukaryotes express repeated copies of three closely related H3 variants,
      inaccessible to genetic analysis. We demonstrate conservation of these phenomena
      in Dictyostelium which has three single-copy H3 variant genes. Although dynamic
      acetylation is targeted to two H3 variants which are K4-trimethylated, K9
      acetylation is preferentially targeted to one. In cells lacking Set1
      methyltransferase and any detectable K4-trimethylation, dynamic acetylation is
      lost demonstrating a direct link between the two. Gene replacement to express
      mutated H3 variants reveals a novel interaction between K4-trimethylation on
      different variants. Cells expressing only one variant show defects in growth, and
      in induction of a UV-inducible gene, demonstrating the functional importance of
      variant expression. These studies confirm that dynamic acetylation targeted to
      H3K4me3 arose early in evolution and reveal a very high level of specificity of
      histone variant utilization in a simple multicellular eukaryote.

PMID- 22600737
TI  - ProBiS-2012: web server and web services for detection of structurally similar
      binding sites in proteins.
AB  - The ProBiS web server is a web server for detection of structurally similar
      binding sites in the PDB and for local pairwise alignment of protein structures.
      In this article, we present a new version of the ProBiS web server that is 10
      times faster than earlier versions, due to the efficient parallelization of the
      ProBiS algorithm, which now allows significantly faster comparison of a protein
      query against the PDB and reduces the calculation time for scanning the entire
      PDB from hours to minutes. It also features new web services, and an improved
      user interface. In addition, the new web server is united with the ProBiS
      Database and thus provides instant access to pre-calculated protein similarity
      profiles for over 29 000 non-redundant protein structures. The ProBiS web server
      is particularly adept at detection of secondary binding sites in proteins. It is
      freely available at http://probis.cmm.ki.si/old-version, and the new ProBiS web
      server is at http://probis.cmm.ki.si.

PMID- 22600738
TI  - PepSite: prediction of peptide-binding sites from protein surfaces.
AB  - Complex biological functions emerge through intricate protein-protein interaction
      networks. An important class of protein-protein interaction corresponds to
      peptide-mediated interactions, in which a short peptide stretch from one partner
      interacts with a large protein surface from the other partner. Protein-peptide
      interactions are typically of low affinity and involved in regulatory mechanisms,
      dynamically reshaping protein interaction networks. Due to the relatively small
      interaction surface, modulation of protein-peptide interactions is feasible and
      highly attractive for therapeutic purposes. Unfortunately, the number of
      available 3D structures of protein-peptide interfaces is very limited. For
      typical cases where a protein-peptide structure of interest is not available, the
      PepSite web server can be used to predict peptide-binding spots from protein
      surfaces alone. The PepSite method relies on preferred peptide-binding
      environments calculated from a set of known protein-peptide 3D structures,
      combined with distance constraints derived from known peptides. We present an
      updated version of the web server that is orders of magnitude faster than the
      original implementation, returning results in seconds instead of minutes or
      hours. The PepSite web server is available at http://pepsite2.russelllab.org.

PMID- 22600739
TI  - jpHMM: recombination analysis in viruses with circular genomes such as the
      hepatitis B virus.
AB  - jpHMM is a very accurate and widely used tool for recombination detection in
      genomic sequences of HIV-1. Here, we present an extension of jpHMM to analyze
      recombinations in viruses with circular genomes such as the hepatitis B virus
      (HBV). Sequence analysis of circular genomes is usually performed on linearized
      sequences using linear models. Since linear models are unable to model
      dependencies between nucleotides at the 5'- and 3'-end of a sequence, this can
      result in inaccurate predictions of recombination breakpoints and thus in
      incorrect classification of viruses with circular genomes. The proposed circular
      jpHMM takes into account the circularity of the genome and is not biased against
      recombination breakpoints close to the 5'- or 3'-end of the linearized version of
      the circular genome. It can be applied automatically to any query sequence
      without assuming a specific origin for the sequence coordinates. We apply the
      method to genomic sequences of HBV and visualize its output in a circular form.
      jpHMM is available online at http://jphmm.gobics.de for download and as a web
      server for HIV-1 and HBV sequences.

PMID- 22600740
TI  - Cyber-T web server: differential analysis of high-throughput data.
AB  - The Bayesian regularization method for high-throughput differential analysis,
      described in Baldi and Long (A Bayesian framework for the analysis of microarray
      expression data: regularized t-test and statistical inferences of gene changes.
      Bioinformatics 2001: 17: 509-519) and implemented in the Cyber-T web server, is
      one of the most widely validated. Cyber-T implements a t-test using a Bayesian
      framework to compute a regularized variance of the measurements associated with
      each probe under each condition. This regularized estimate is derived by flexibly
      combining the empirical measurements with a prior, or background, derived from
      pooling measurements associated with probes in the same neighborhood. This
      approach flexibly addresses problems associated with low replication levels and
      technology biases, not only for DNA microarrays, but also for other technologies,
      such as protein arrays, quantitative mass spectrometry and next-generation
      sequencing (RNA-seq). Here we present an update to the Cyber-T web server,
      incorporating several useful new additions and improvements. Several
      preprocessing data normalization options including logarithmic and (Variance
      Stabilizing Normalization) VSN transforms are included. To augment two-sample t
      tests, a one-way analysis of variance is implemented. Several methods for
      multiple tests correction, including standard frequentist methods and a
      probabilistic mixture model treatment, are available. Diagnostic plots allow
      visual assessment of the results. The web server provides comprehensive
      documentation and example data sets. The Cyber-T web server, with R source code
      and data sets, is publicly available at http://cybert.ics.uci.edu/.

PMID- 22600741
TI  - Repetitive elements and enforced transcriptional repression co-operate to enhance
      DNA methylation spreading into a promoter CpG-island.
AB  - Repression of many tumor suppressor genes in cancer is concurrent with aberrantly
      increased DNA methylation levels at promoter CpG islands (CGIs). About one-fourth
      of empirically defined human promoters are surrounded by or contain clustered
      repetitive elements. It was previously observed that a sharp transition of
      methylation exists between highly methylated repetitive elements and unmethylated
      promoter-CGIs in normal tissues. The factors that lead to aberrant CGI
      hypermethylation in cancer remain poorly understood. Here, we established a site
      specific integration system with enforced local transcriptional repression in
      colorectal cancer cells and monitored the occurrence of initial de novo
      methylation at specific CG sites adjacent to the CGI of the INSL6 promoter, which
      could be accelerated by binding a KRAB-containing transcriptional factor.
      Additional repetitive elements from P16 and RIL (PDLIM4), if situated adjacent to
      the promoter of INSL6, could confer DNA methylation spreading into the CGI
      particularly in the setting of KRAB-factor binding. However, a repressive
      chromatin alone was not sufficient to initiate DNA methylation, which required
      specific DNA sequences and was integration-site (and/or cell-line) specific.
      Overall, these results demonstrate a requirement for specific DNA sequences to
      trigger de novo DNA methylation, and repetitive elements as cis-regulatory
      factors to cooperate with advanced transcriptional repression in promoting
      methylation spreading.

PMID- 22600742
TI  - O-miner: an integrative platform for automated analysis and mining of -omics
      data.
AB  - High-throughput profiling has generated massive amounts of data across basic,
      clinical and translational research fields. However, open source comprehensive
      web tools for analysing data obtained from different platforms and technologies
      are still lacking. To fill this gap and the unmet computational needs of ongoing
      research projects, we developed O-miner, a rapid, comprehensive, efficient web
      tool that covers all the steps required for the analysis of both transcriptomic
      and genomic data starting from raw image files through in-depth bioinformatics
      analysis and annotation to biological knowledge extraction. O-miner was developed
      from a biologist end-user perspective. Hence, it is as simple to use as possible
      within the confines of the complexity of the data being analysed. It provides a
      strong analytical suite able to overlay and harness large, complicated, raw and
      heterogeneous sets of profiles with biological/clinical data. Biologists can use
      O-miner to analyse and integrate different types of data and annotations to build
      knowledge of relevant altered mechanisms and pathways in order to identify and
      prioritize novel targets for further biological validation. Here we describe the
      analytical workflows currently available using O-miner and present examples of
      use. O-miner is freely available at www.o-miner.org.

PMID- 22601779
TI  - Obestatin regulates adipocyte function and protects against diet-induced insulin
      resistance and inflammation.
AB  - The metabolic actions of the ghrelin gene-derived peptide obestatin are still
      unclear. We investigated obestatin effects in vitro, on adipocyte function, and
      in vivo, on insulin resistance and inflammation in mice fed a high-fat diet
      (HFD). Obestatin effects on apoptosis, differentiation, lipolysis, and glucose
      uptake were determined in vitro in mouse 3T3-L1 and in human subcutaneous (hSC)
      and omental (hOM) adipocytes. In vivo, the influence of obestatin on glucose
      metabolism was assessed in mice fed an HFD for 8 wk. 3T3-L1, hSC, and hOM
      preadipocytes and adipocytes secreted obestatin and showed specific binding for
      the hormone. Obestatin prevented apoptosis in 3T3-L1 preadipocytes by increasing
      phosphoinositide 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase
      (ERK)1/2 signaling. In both mice and human adipocytes, obestatin inhibited
      isoproterenol-induced lipolysis, promoted AMP-activated protein kinase
      phosphorylation, induced adiponectin, and reduced leptin secretion. Obestatin
      also enhanced glucose uptake in either the absence or presence of insulin,
      promoted GLUT4 translocation, and increased Akt phosphorylation and sirtuin 1
      (SIRT1) protein expression. Inhibition of SIRT1 by small interfering RNA reduced
      obestatin-induced glucose uptake. In HFD-fed mice, obestatin reduced insulin
      resistance, increased insulin secretion from pancreatic islets, and reduced
      adipocyte apoptosis and inflammation in metabolic tissues. These results provide
      evidence of a novel role for obestatin in adipocyte function and glucose
      metabolism and suggest potential therapeutic perspectives in insulin resistance
      and metabolic dysfunctions.

PMID- 22602825
TI  - Dermatomyositis and chest radiography leading to the diagnosis of lung cancer and
      subsequent confusions in staging due to the presence of tuberculosis.
AB  - This clinical scenario describes dermatomyositis as a presenting feature of
      carcinoma of the lung. However, the coincident existence of tuberculosis in the
      opposite lung gave rise to a false impression of contralateral lung metastasis
      and hence confusions with regard to staging ensued, which were clarified after
      further investigation confirmed a unilateral lung adenocarcinoma and
      contralateral tuberculosis. The patient was initiated on oral antiepidermal
      growth factor receptor therapy with erlotinib, as well as on multi-drug therapy
      for tuberculosis. This report intends to illustrate that paraneoplastic syndromes
      such as dermatomyositis can be the presenting feature of lung cancer, and also
      that the co-incident presence of carcinoma and tuberculosis can cause confusions
      with regard to staging and management.

PMID- 22602826
TI  - Crohn's disease or TB--the perennial question and diagnostic pitfalls.
AB  - A previously healthy 28-year old lady from Saudi Arabia presented with recurrent
      peri-anal abscesses progressing to fistula-in-ano. These were treated with
      incision and drainages and with setonisation of the fistula. Multiple biopsy and
      culture specimens were taken to rule out tuberculosis (TB) or Crohn's disease -
      all showed granulomatous disease suggestive of either Crohn's or TB, no
      mycobacteria were grown. MRI scanning also suggested either TB or Crohn's
      disease. Tuberculin skin test was inconclusive and Quantiferon Gold test was
      negative. Treatment for Crohn's was started with oral prednisolone - the patient
      deteriorated and adalimumab (tumour necrosis factor alpha antagonist) was
      commenced. With continued deterioration in the absence of intra-abdominal
      abscesses, a clinical diagnosis of TB was made, Crohn's treatment suspended and
      quadruple therapy for TB was initiated. The patient rapidly improved and a
      delayed re-look histological specimen identified an isolated mycobacterium.
      Subsequent cultures confirmed drug-sensitive TB. The lady is currently well on TB
      eradication regimen.

PMID- 22601780
TI  - The RGD finger of Del-1 is a unique structural feature critical for integrin
      binding.
AB  - Developmental endothelial cell locus-1 (Del-1) glycoprotein is secreted by
      endothelial cells and a subset of macrophages. Del-1 plays a regulatory role in
      vascular remodeling and functions in innate immunity through interaction with
      integrin alpha(V)beta(3). Del-1 contains 3 epidermal growth factor (EGF)-like
      repeats and 2 discoidin-like domains. An Arg-Gly-Asp (RGD) motif in the second
      EGF domain (EGF2) mediates adhesion by endothelial cells and phagocytes. We
      report the crystal structure of its 3 EGF domains. The RGD motif of EGF2 forms a
      type II' beta turn at the tip of a long protruding loop, dubbed the RGD finger.
      Whereas EGF2 and EGF3 constitute a rigid rod via an interdomain calcium ion
      binding site, the long linker between EGF1 and EGF2 lends considerable
      flexibility to EGF1. Two unique O-linked glycans and 1 N-linked glycan locate to
      the opposite side of EGF2 from the RGD motif. These structural features favor
      integrin binding of the RGD finger. Mutagenesis data confirm the importance of
      having the RGD motif at the tip of the RGD finger. A database search for EGF
      domain sequences shows that this RGD finger is likely an evolutionary insertion
      and unique to the EGF domain of Del-1 and its homologue milk fat globule-EGF 8.

PMID- 22602827
TI  - Natural history of a giant abdominal lipoma.

PMID- 22602828
TI  - Limping man--unusual presentation of lung carcinoma.
AB  - The authors report a case of a 61-year-old male smoker with primary
      adenocarcinoma of the lung with brain metastases. He presented with a 2 month
      history of a gradually worsening unilateral limp with no other local or systemic
      symptoms. History and examination findings suggested an upper motor neuron lesion
      but failed to indicate the level of the pathology. On further investigation, a
      mass was found in the upper lobe of the left lung and two ring-enhancing brain
      lesions. With surgical intervention ruled out, he was commenced on high dose
      dexamethasone and is currently undergoing palliative whole brain radiotherapy.

PMID- 22602829
TI  - Septic arthritis of unilateral lumbar facet joint with contiguous abscess,
      without prior intervention.
AB  - A 40-year-old female patient presented with persistent severe back pain radiating
      to the right leg, abdominal pain and constipation. Other clinical symptoms
      included nausea, vomiting and high-grade fever. Clinical examination showed
      generalised abdominal and lower back tenderness. There was no sensory loss or
      motor weakness in lower limbs, however investigations showed raised inflammatory
      markers. Radiographs of the lumbar spine and hip joint were normal. MRI revealed
      a septic arthritis of the right L3/4 facet joint, associated with a large abscess
      extending anteriorly to the right paraspinal muscles and posteriorly into the
      right posterolateral aspect of the epidural space in the central spinal canal,
      with moderate compression of the dural sac. Unlike any other reported similar
      case, this septic arthritis developed without prior medical intervention. The
      patient was treated successfully with ultrasound guided drainage of the facet
      joint/abscess and antibiotics.

PMID- 22602830
TI  - Diaphyseal desmoplastic fibroma of humerus--report of a rare presentation.
AB  - Desmoplastic fibroma is a rare locally aggressive benign tumour. It is most
      frequently reported in mandible, metaphysis and metadiaphysis of long bones. This
      tumour has been observed infrequently in the diaphysis like the one presented
      here. An 18-year-old female presented with progressive swelling left arm and dull
      aching pain for 1 year. She had a bony hard lobular well-defined swelling in the
      midshaft of humerus, which was not warm but tender. There was abnormal mobility
      present indicating a fracture. Plain radiograph of the affected arm showed an
      expansile, well-defined, intraosseous, radiolucent lesion with expansion
      involving the entire circumference of the humerus. An open biopsy was carried out
      and the report came out to be desmoplastic fibroma. She underwent wide segmental
      resection and interlocking nailing and bone grafting. After 6 weeks follow-up,
      the patient had visible callus and by 12 weeks there was significant union.

PMID- 22602831
TI  - Tuberculous radiculomyelitis presenting as urinary retention in a child with
      Down's syndrome.
AB  - Tuberculous radiculomyelitis (TBRM) is an uncommon complication of TB meningitis.
      The authors report the case of a 10-year-old Asian girl with trisomy 21, who
      presented with acute urinary retention and fever. She was initially treated for a
      urinary tract infection. After an acute neurological deterioration she was found
      to have evidence of TB meningitis with TBRM. She developed acute hydrocephalus
      requiring ventriculo-peritoneal shunt. She was treated with quadruple
      antituberculous therapy and high dose intravenous dexamethasone. She needed
      tracheostomy with continuous positive airway pressure (CPAP) support. Although
      she showed gradual neurological improvement in her cognitive functions, she
      persisted to have quadriparesis with the need for tracheostomy and CPAP support
      overnight and gastrostomy feeding. Acute urinary retention in children is
      uncommon, and should serve as a 'red flag' to consideration of further underlying
      neurological problems. This presentation and subsequent events should serve as a
      learning point to clinicians.

PMID- 22602832
TI  - Fluctuating neurological symptoms in demyelinating disease mimicking an acute
      ischaemic stroke.
AB  - Fluctuating neurological symptoms in an older patient most often point towards a
      cerebral ischaemic pathology. The authors present a 66-year-old male patient
      suffering from a fluctuating right hemiparesis, with an initial diagnosis of
      ischaemic stroke. The brain and cervical MRI showed demyelinating lesions with
      abnormal cerebrospinal fluid (CSF) and visual evoked potentials and the patient
      was successfully treated with intravenous corticosteroids. Demyelinating disease
      in older patients could be more frequent than expected. It should be considered
      even in older patients with fluctuating neurological symptoms. MRI and CSF
      analysis are critical to provide an accurate diagnosis.

PMID- 22602833
TI  - Epithelioid leiomyosarcoma of uterus.
AB  - Fibroid most commonly presents in the reproductive age group and presence of
      fibroid with postmenopausal bleeding is a rare entity and all investigations and
      measures should be done to rule out leiomyosarcoma. A 45-year-old female had
      attained menopause 3 year back and developed postmenopausal bleeding since 2
      months, with palpable mass, of 24 weeks size. Ultrasonography showed multiple
      whorled mass lesions, endometrium and myometrium could not be seen separately.
      Total abdominal hysterectomy with bilateral salpingoophorectomy was performed.
      Intraoperative findings showed 24 weeks uterine mass with size 17.5*15.5*11.5 cm
      and weight 1.9 kg with multiple, intramural fibroids. Cut section of removed
      specimen showed black and yellow necrotic and haemorrhagic areas with
      degenerative changes suggestive of malignancy. Histopathology reported
      epithelioid leiomyosarcoma.

PMID- 22602834
TI  - Acute accidental phosgene poisoning.
AB  - Phosgene is a highly toxic gas to which accidental exposure may occur in
      occupational workers. This case report describes the clinical presentation and
      management of accidental phosgene poisoning happened after the leakage of
      phosgene gas from nearby pipeline. The need to suspect phosgene gas exposure and
      observe such patients is crucial for life saving, especially in view of the delay
      in clinical deterioration observed in some patients who subsequently develop
      adult respiratory distress syndrome.

PMID- 22602836
TI  - Asymptomatic double aortic arch with compressed oesophagus in an adult.

PMID- 22602835
TI  - Incidence of CMV-HCV coinfection in renal transplant recipient.
AB  - The authors report a case of a 47-year-old cytomegalovirus (CMV) immunoglobulin G
      (IgG) seropositive male patient with end stage renal disease who received a live
      renal transplant from a CMV IgG seropositive donor. Six months post
      transplantation, the patient presented with reduced renal allograft function
      associated with fever, severe breathlessness, new onset jaundice and
      pancytopenia. His CMV DNA PCR came positive. Hepatitis C virus (HCV) RNA PCR also
      came positive (genotype I) though anti-HCV test performed before and after
      transplantation was negative. The patient was treated with oral valganciclovir
      and showed improvement of his clinical condition and was subsequently discharged
      under supervised therapy. However, the patient could not be treated for HCV
      because of risk of renal allograft rejection. The authors suggest oral
      valganciclovir for management of CMV infection and proper detection and
      eradication of HCV before renal transplantation to avoid future complications and
      prolongation of allograft survival.

PMID- 22602837
TI  - Neonatal liver failure due to deoxyguanosine kinase deficiency.
AB  - Deoxyguanosine kinase (dGK) deficiency, a rare severe cause of mitochondrial DNA
      (mtDNA) depletion, has two forms of presentation: hepatocerebral syndrome and
      isolated hepatic disease. The authors report three cases with neonatal liver
      failure due to dGK deficiency. Consanguinity was present in all patients. One
      patient had a brother who died with a probable diagnosis of neonatal
      haemochromatosis. All patients had progressive cholestatic liver failure,
      hypoglycaemia, hyperlactacidaemia, elevated ferritin levels and nystagmus, since
      first day of life. Liver tissue study revealed: cholestasis, iron deposits,
      microvesicular steatosis and fibrosis/cirrhosis. Only one patient was submitted
      to liver transplantation. The other two died, at 2 and 5 months of age. mtDNA
      quantification and DGUOK gene study should be considered in infants/neonates with
      acute liver failure and systematically performed in patients with hepatocerebral
      presentation. Differential diagnosis with neonatal haemochromatosis is needed.
      Liver transplantation might be a therapeutic option. Early diagnosis is important
      for genetic counselling.

PMID- 22602838
TI  - Abdominal compartment syndrome--a fatal complication from a rectus sheath
      haematoma.
AB  - Rectus sheath haematoma is increasingly being seen in patients with
      anticoagulation therapy. Abdominal compartment syndrome is a rare complication of
      rectus sheath haematoma with only two cases reported in literature. The authors
      report a case of a young male who developed abdominal compartment syndrome from a
      rectus sheath haematoma secondary to anticoagulation therapy. The case highlights
      the need for a surgical intervention in such exceptional cases.

PMID- 22602839
TI  - Juvenile gout: rare and aggressive.

PMID- 22602840
TI  - Failure of knee arthroplasty secondary to inadequate technique in
      cephalomedullary nailing of a subtrochanteric hip fracture.
AB  - A case of total knee replacement loosening caused by a failed cephalomedullary
      nail is presented. The nail was inserted for the treatment of an unstable
      subtrochanteric femoral fracture. The distal locking screw of the nail
      subsequently fractured allowing the leg to shorten and causing the nail to
      displace the femoral component of the knee replacement leading to a valgus
      alignment and deformity of the knee. In order to revise the knee the long gamma
      nail had to be replaced by a shorter nail to allow a femoral component with a
      long stem to be used. This case illustrates the importance of using shorter nails
      in patients with prosthetic knees.

PMID- 22602841
TI  - Mycobacterium malmoense: dissemination causes a popliteal aneurysm in a 74-year
      old man.
AB  - Mycobacterium malmoense is recognised as an environmental pathogen predominantly
      affecting populations in Northern Europe. In immuno-competent individuals,
      isolated pulmonary disease remains the commonest presentation. The authors report
      a rare case describing a mycotic popliteal aneurysm caused by M malmoense in a 74
      year-old man from Hastings, UK with co-existing pulmonary M malmoense disease.
      Primary pulmonary disease was confirmed by a combination of history, examination
      and positive radiological and microbiological findings. Tissue analysis of the
      aneurysm wall during popliteal aneurysm repair confirmed the presence of
      disseminated M malmoense. Histological analysis of the aneurysm wall showed non
      caseating granulomata. The patient completed a 2 year course of rifampicin,
      ethambutol and clarithromycin which eradicated the organism from his sputum.
      Further progress has been complicated by the development of an aspergilloma at
      the site of his eradicated pulmonary M malmoense disease and the need for
      angioplasty to his bypass grafts 1 year postsurgery.

PMID- 22603793
TI  - Alteration of chi recognition by RecBCD reveals a regulated molecular latch and
      suggests a channel-bypass mechanism for biological control.
AB  - The RecBCD enzyme is a complex heterotrimeric helicase/nuclease that initiates
      recombination at double-stranded DNA breaks. In Escherichia coli, its activities
      are regulated by the octameric recombination hotspot, chi (5'-GCTGGTGG), which is
      read as a single-stranded DNA sequence while the enzyme is unwinding DNA at over
      ~1,000 bp/s. Previous studies implicated the RecC subunit as the "chi-scanning
      element" in this process. Site-directed mutagenesis and phenotypic analyses
      identified residues in RecC responsible for chi recognition [Handa N, et al.,
      (2012) Proc Natl Acad Sci USA, 10.1073/pnas.1206076109]. The genetic analyses
      revealed two classes of mutants. Here we use ensemble and single-molecule
      criteria to biochemically establish that one class of mutants (type 1) has lost
      the capacity to recognize chi (lost-recognition), whereas the second class (type
      2) has a lowered specificity for recognition (relaxed-specificity). The relaxed
      specificity mutants still recognize canonical chi, but they have gained the
      capacity to precociously recognize single-nucleotide variants of chi. Based on
      the RecBCD structure, these mutant classes define an alpha-helix responsible for
      chi recognition that is allosterically coupled to a structural latch. When
      opened, we propose that the latch permits access to an alternative exit channel
      for the single-stranded DNA downstream of chi, thereby avoiding degradation by
      the nuclease domain. These findings provide a unique perspective into the
      mechanism by which recognition of a single-stranded DNA sequence switches the
      translocating RecBCD from a destructive nuclease to a constructive component of
      recombinational DNA repair.

PMID- 22603794
TI  - Molecular determinants responsible for recognition of the single-stranded DNA
      regulatory sequence, chi, by RecBCD enzyme.
AB  - The RecBCD enzyme is important for both restriction of foreign DNA and
      recombinational DNA repair. Switching enzyme function from the destructive
      antiviral state to the productive recombinational state is regulated by the
      recombination hotspot, chi (5'-GCTGGTGG-3'). Recognition of chi is unique in that
      it is recognized as a specific sequence within single-stranded DNA (ssDNA) during
      DNA translocation and unwinding by RecBCD. The molecular determinants of chi
      recognition and the subsequent alteration in function are unknown. Consequently,
      we mutated residues within the RecC subunit that comprise a channel where ssDNA
      is thought to be scanned for a chi sequence. These mutants were characterized in
      vivo with regard to chi recognition, UV-sensitivity, phage degradation, and
      recombination proficiency. Of 38 residues mutated, 11 were previously undescribed
      mutations that altered chi recognition. The mutants fell into two classes: five
      that failed to respond to chi, and six that suggested a relaxed specificity for
      chi recognition. The location of the first set of mutations defines a recognition
      structure responsible for sequence-specific binding of ssDNA. The second set
      defines a highly conserved structure, linked to the recognition structure, which
      we hypothesize regulates conversion of RecBCD from a molecular machine that
      destroys DNA to one that repairs it. These findings offer insight into the
      evolution of enzymes with alternate chi recognition specificities.

PMID- 22603796
TI  - Voltage-sensor cycle fully described.

PMID- 22603978
TI  - Animal models of retinal injury.
AB  - Retinal  injury is a common cause of profound and intractable loss of vision.
      Clinical outcomes are poor in both open and closed globe injuries because cell
      death, scarring, and a failure of tissue and axon regeneration are not
      ameliorated by current treatments. Much animal research is directed at
      understanding and modifying these pathologies, although results have yet to
      translate into clinical practice. Axotomy-induced retinal ganglion cell (RGC)
      death in mammals can be effectively reduced and axon regeneration enhanced over
      the short term. After retinal injury in mammals, the retinal pigment epithelium
      (RPE) and retinal glia either regenerate lost RPE and neuroretinal cells or form
      nonfunctional scars. An understanding of the mechanisms underlying injury
      responses is critical to the successful development of therapeutic strategies to
      promote ocular repair.

PMID- 22603795
TI  - Evidence for a functional role of epigenetically regulated midcluster HOXB genes
      in the development of Barrett esophagus.
AB  - Barrett esophagus (BE) is a human metaplastic condition that is the only known
      precursor to esophageal adenocarcinoma. BE is characterized by a posterior
      intestinal-like phenotype in an anterior organ and therefore it is reminiscent of
      homeotic transformations, which can occur in transgenic animal models during
      embryonic development as a consequence of mutations in HOX genes. In humans,
      acquired deregulation of HOX genes during adulthood has been linked to
      carcinogenesis; however, little is known about their role in the pathogenesis of
      premalignant conditions. We hypothesized that HOX genes may be implicated in the
      development of BE. We demonstrated that three midcluster HOXB genes (HOXB5,
      HOXB6, and HOXB7) are overexpressed in BE, compared with the anatomically
      adjacent normal esophagus and gastric cardia. The midcluster HOXB gene signature
      in BE is identical to that seen in normal colonic epithelium. Ectopic expression
      of these three genes in normal squamous esophageal cells in vitro induces markers
      of intestinal differentiation, such as KRT20, MUC2, and VILLIN. In BE-associated
      adenocarcinoma, the activation midcluster HOXB gene is associated with loss of
      H3K27me3 and gain of AcH3, compared with normal esophagus. These changes in
      histone posttranslational modifications correlate with specific chromatin
      decompaction at the HOXB locus. We suggest that epigenetically regulated
      alterations of HOX gene expression can trigger changes in the transcriptional
      program of adult esophageal cells, with implications for the early stages of
      carcinogenesis.

PMID- 22604197
TI  - Intra and extra-hepatic cystadenoma of the biliary duct. Review of literature and
      radiological and pathological characteristics of a very rare case.
AB  - Painless obstructive jaundice is often associated with a malignant disease of the
      common bile duct or head of the pancreas. The authors present a unique case of a
      62-year-old woman affected by an intrahepatic cystadenoma that extended into the
      common biliary duct. To our knowledge no previous case reports have been
      published on similar cases. After undergoing an en-block hepatic and bile duct
      resection, this patient is doing well without signs of recurrent disease.

PMID- 22604198
TI  - Acquired haemophilia secondary to ivabradine presenting with acute respiratory
      distress syndrome.
AB  - The authors present the case of a 72-year-old patient who presented with severe
      dyspnoea, scant haemoptysis, pronounced desaturation and bilateral haematomas on
      the upper limbs. Chest radiography showed bilateral infiltrates mainly in the
      lower lobes. The patient's prothrombin time, and platelet count were normal.
      However, the activated partial thromboplastin time showed a prolongation that was
      not reversed on a correction study. Factor VIII (FVIII) levels were very low and
      evidence of FVIII inhibitor was found. The patient had started taking ivabradine
      2 months earlier, and the diagnosis of idiosyncratic acquired haemophilia was
      established. The patient was treated with volume expansion therapy, high levels
      of oxygen, multiple transfusions, methylprednisolone, desmopressine and
      rituximab. On the 3rd day, the patient showed progressive amelioration of his
      dyspnoea, oxygen needs and chest infiltrates. On the 7th day, the patient was
      discharged.

PMID- 22604199
TI  - Tension pneumoperitoneum complicated with tension pneumothorax in a patient with
      diaphragmatic eventration.
AB  - Tension pneumothorax complicating a pneumoperitoneum is a rare but known entity.
      However, all previously published articles report an air leak through defects in
      the diaphragm connecting the pneumoperitoneum and the pneumothorax. Here, the
      case of a 36-year-old man in whom the pneumoperitoneum acted like a tension
      pneumothorax because of a congenital eventration of the left diaphragm without
      penetration is presented. Emergency needle decompression of the abdomen was
      performed. A gastric ulcer that had passed through the diaphragm to the right
      lung was diagnosed intraoperatively. Unfortunately, the patient developed a
      ventricular fibrillation that remained resistant to all resuscitative efforts,
      and the patient died shortly afterwards.

PMID- 22604200
TI  - Metastasis of carcinoma of the lung to a carotid body paraganglioma.
AB  - Tumour-to-tumour metastasis is a rare phenomenon, but has been described in the
      literature in just over 100 cases. It can be particularly puzzling for the
      reporting pathologists, when encountered unexpectedly in a tumour showing abrupt
      transition from the usual morphology to another unusual pattern. The literature
      reports a variety of combinations with carcinoma-to-carcinoma being the most
      common; and renal cell carcinomas appear to the most common recipient tumours
      with common donor tumours being breast, lung and renal cell carcinomas. The
      authors report a case of poorly-differentiated lung carcinoma metastasising into
      a carotid body paraganglioma. Our case is unique and in our knowledge the first
      described case of carotid body paraganglioma with metastasis from a lung primary.
      To the best of our knowledge this is the first report of this interesting
      biological phenomenon in this combination.

PMID- 22604201
TI  - Electrocution-induced atrial fibrillation: a novel cause of a familiar
      arrhythmia.
AB  - A previously fit and well 40-year-old man presented to the emergency department
      with palpitations after suffering an 11 000 volt electrical shock from overhead
      power cables through a mobile crane which he was operating. His ECG demonstrated
      the presence of new atrial fibrillation at a rate of 80 beats per min. He was
      haemodynamically stable, and had otherwise only sustained a small exit burn to
      his left great toe. Routine blood tests including creatine kinase and troponin T
      were normal. A bolus of intravenous flecainide failed to restore sinus rhythm,
      but an amiodarone infusion was successful. An electrical shock is a rare cause of
      atrial fibrillation. There is no consensus over optimal medical management.
      Numerous treatment plans have been previously employed with varying degrees of
      success.

PMID- 22604202
TI  - Efficacy of ECT in severe obsessive-compulsive disorder with Parkinson's disease.
AB  - A man in his 60's was admitted following a serious suicide attempt secondary to
      severe obsession with bowel movements and severe depression. He had multiple
      previous admissions with similar presentations and responded partially to
      psychotropic medications. It was transpired that obsessive compulsive disorder
      preceded depression and being overwhelmed with this obsession related to bowel
      movement, he decided to end his life. Electro-convulsive therapy was commenced
      with good results. His obsessive-compulsive disorder came under control to a
      greater extent and there was an improvement in his mood.

PMID- 22604203
TI  - A complicated simple fall--an atypical case of serogroup Y meningococcal
      pneumonia with secondary septicaemia and literature review.
AB  - An elderly lady was admitted for pain management and rehabilitation following a
      fall. During her stay she developed a new heart murmur and sepsis. Subacute
      bacterial endocarditits was excluded, empirical ciprofloxacin was initiated and
      later converted to aztreonam with gentamicin for clinical deterioration.
      Subsequent investigations revealed meningococcal Y septicaemia secondary to
      pneumonia, with a possible oropharynx focus. Upon discharge she had returned to
      baseline state. The case reflects an unusual and increasing cause of pneumonia. A
      steady increase of infective serogroup Y isolates over the past 12-years in
      England, with tendency towards elderly makes it a significant differential among
      the general medical population. This trend corresponds with the US, but is yet
      unknown whether to be a periodic cycle or true change in dominance and, or,
      virulence among serogroups. If the latter were true, it would support the
      inclusion of serogroups beyond menigitides C in the vaccination program.

PMID- 22604204
TI  - Nosocomial meningitis caused by gas producing Klebsiella pneumoniae.
AB  - A 40-year-old woman presented with dyspnoea and lowered level of consciousness.
      Three months before presentation she had underwent craniotomy for an episode of
      acute subdural hematoma caused by a severe neurotrauma. Her temperature was 37.3
      degrees C, she had no focal neurological deficits or neck stiffness, and the
      score on the Glasgow Coma Scale was 9 (E2M5V2). Cranial CT showed obstruction
      hydrocephalus with hypodensities consistent with airbubbles in the lateral
      ventricles, but no air in the proximity of the skull defect resulting from the
      craniotomy. External ventricular drainage was performed and cerebrospinal fluid
      (CSF) examination showed 126 327 leucocytes per MUl, a protein level of 26.28 g/l
      and a glucose level of <0.1 mmol/l. CSF culture grew Klebsiella pneumoniae, a gas
      producing bacterium. Despite antibiotic treatment with meropenem, ceftriaxone and
      intraventricular gentamicin and supportive therapy, our patient deteriorated and
      died 3 weeks after admission. The family did not give consent for autopsy.

PMID- 22604205
TI  - An unusual cause of limp.
AB  - Limp is a common clinical presentation in children, seen both in acute and
      community practice. The incidence is thought to vary between countries with
      suggested figures between 1.5 and 3.6 cases of non-traumatic limp per 1000
      children. The authors present a case of a 6-year-old girl who attended our
      accident and emergency department with limp. It has been suggested that the most
      common diagnoses in our patient's age group are transient synovitis, septic
      arthritis, osteomyelitis, Perthe's disease and fractures or soft tissue injuries.
      Surprisingly our patient was diagnosed with haemophagocytic lymphohistiocytosis,
      for which limp is not a recognised presenting feature.

PMID- 22604271
TI  - User satisfaction with maritime telemedicine.
AB  - We assessed the satisfaction of onboard caregivers with the maritime telehealth
      service provided by the Centre de Consultations Medicales Maritimes (CCMM). We
      conducted a survey of captains and caregivers by email. Of the 385 surveys sent
      out, 165 (43%) were completed. Eighty four percent of responders (n = 110)
      thought that waiting time was satisfactory or very satisfactory, and 97% (n =
      128) were satisfied or very satisfied with their relationship with the remote
      physician. Thirty eight per cent of participants (n = 50) considered that the
      physician understood the medical problem very well; understanding was good in 58%
      of cases (n = 76) and bad in only 4% of cases (n = 5). Sixty two per cent of
      participants (n = 83) sent pictures before consultation. The respondents were
      also satisfied with the telephone advice overall, the competence of the
      physicians providing the advice, the length of time spent waiting, the verbal
      prescription and the medical advice given. Onboard caregivers were generally well
      satisfied with the maritime teleconsultations and the advice provided by the CCMM
      physicians.

PMID- 22604272
TI  - A solution for delay and survival in bladder cancer: the use of reminder text
      messages.

PMID- 22604273
TI  - Near real-time echocardiography teleconsultation using low bandwidth and MPEG-4
      compression: feasibility, image adequacy and clinical implications.
AB  - We assessed the feasibility, image adequacy and clinical utility of a tele
      echocardiography service which combined video compression with low-bandwidth
      store-and-forward transmission. Echocardiograms were acquired by a hospital
      geriatrician, compressed and transmitted using both near real-time (urgent) and
      delayed (pre-programmed) protocols via an Internet connection to the notebook PC
      of a remote cardiologist. Clinical utility was evaluated as a change in
      therapeutic management. During a one-year period, 101 tele-echocardiography
      consultations were successfully performed (feasibility = 100%) on 95 patients
      (age 22-95 years), admitted with cardiovascular or neurological diagnoses (24% of
      the consultations were urgent). In total, 4617 files (1.4 GByte of data) were
      transmitted, 2669 of which were short video clips. On average, 46 files (13.8
      MByte) were transmitted (mean duration 10 min) at each examination. Consultations
      (both urgent and pre-programmed) were clinically useful in 83% of examinations.
      Logistic regression analysis showed that both a low left ventricular systolic
      function and the examination indication were determinants of clinical utility.
      The transmitted images were considered adequate for diagnosis in 100% of the pre
      programmed teleconsultations. Tele-echocardiography using MPEG-4 video
      compression is a feasible, adequate and clinically useful tool for telemedicine.

PMID- 22604274
TI  - HIV education and counselling using Facebook: a possible new approach.

PMID- 22604275
TI  - Telemonitoring, COPD and cough counting.

PMID- 22604276
TI  - ECG telemonitoring during home-based cardiac rehabilitation in heart failure
      patients.
AB  - We assessed ECGs recorded during home-based telemonitored cardiac rehabilitation
      (HTCR) in stable patients with heart-failure. The study included 75 patients with
      heart failure (NYHA II, III), with a mean age of 56 years. They participated in
      an eight-week programme of home cardiac rehabilitation which was telemonitored
      with a device which recorded 16-s fragments of their ECG. These fragments were
      transmitted via mobile phone to a monitoring centre. The times of the automatic
      ECG recordings were pre-set and coordinated with the cardiac rehabilitation.
      Patients were able to make additional recordings when they felt unwell using a
      tele-event-Holter ECG facility. During the study, 5757 HTCR sessions were
      recorded and 11,534 transmitted ECG fragments were evaluated. Most ECGs
      originated from the automatic recordings. Singular supraventricular and
      ventricular premature beats and ventricular couplets were detected in 16%, 69%
      and 16% of patients, respectively. Twenty ECGs were recorded when patients felt
      unwell: non sustained ventricular tachycardia occurred in three patients and
      paroxysmal atrial fibrillation episode in two patients. Heart failure patients
      undergoing HTCR did not develop any arrhythmia which required a change of the
      procedure, confirming it was safe. Cardiac rehabilitation at home was improved by
      utilizing the tele-event-Holter ECG facility.

PMID- 22604277
TI  - Assessing children's speech intelligibility and oral structures, and functions
      via an Internet-based telehealth system.
AB  - We examined the validity and reliability of an Internet-based telehealth system
      for screening speech intelligibility and oro-motor structure, and function in
      children with speech disorders. Twenty children aged 4-9 years were assessed by a
      clinician in the conventional, face-to-face (FTF) manner; simultaneously, they
      were assessed by a second clinician via the videoconferencing system using a 128
      kbit/s Internet connection. Speech intelligibility in conversation was rated and
      an informal assessment of oro-motor structure and function was conducted. There
      was a high level of agreement between the online and FTF speech intelligibility
      ratings, with 70% exact agreement and 100% close agreement (within +/- point on a
      5-point scale). The weighted kappa statistic revealed very good agreement between
      raters (kappa = 0.86). Data for online and FTF ratings of oro-motor function
      revealed overall exact agreement of 73%, close agreement of 96%, moderate or good
      strength of agreement for six variables (kappa = 0.48-0.74), and poor to fair
      agreement for six variables (kappa = 0.12-0.36). Intra- and inter-rater
      reliability measures (ICCs) were similar between the online and FTF assessments.
      Low levels of agreement for some oro-motor variables highlighted the subjectivity
      of this assessment. However, the overall results support the validity and
      reliability of Internet-based screening of speech intelligibility and oro-motor
      function in children with speech disorders.

PMID- 22604278
TI  - An evaluation of diabetes self-management applications for Android smartphones.
AB  - We reviewed diabetes apps for Android smartphones. We compiled a list of free and
      paid apps in April 2011 by searching the Android Market for apps which could
      track self-monitoring of blood glucose (SMBG), diabetes medications or calculate
      prandial insulin dosages. Two reviewers independently evaluated six features per
      app, using a five-point Likert scale. The sum of the six ratings was the
      composite usability score, and the mean score of an app's features was the
      average usability score. Of the 80 Android diabetes apps identified, 42 unique
      apps were eligible for the study. SMBG recording was present in 36 (86%) of the
      apps, a tool to track insulin or oral diabetic medications was found in 19 (45%)
      apps, and a prandial insulin dose calculator existed for 11 (26%) apps. Eighteen
      apps were free of charge and the other 24 apps had a mean purchase price of $2.86
      (range 0.99-6.99). The mean composite usability score was 11.3 out of a possible
      30. The mean average usability score was 3.0 out of a possible 5.0. Only four of
      the 42 apps had a composite usability score above 20 and none offered direct data
      input from glucometers, suggesting that few provided a comprehensive method of
      diabetes management. The apps Glucool Diabetes, OnTrack Diabetes, Dbees and
      Track3 Diabetes Planner were the highest rated. Clinicians may find it useful to
      recommend these apps.

PMID- 22604279
TI  - A survey of telehealth coordinators in Canada.
AB  - Telehealth coordinators practising in Canada were invited to respond to an online
      survey and participate in a telephone interview. For the present study, the
      definition of 'telehealth' was limited to the use of videoconferencing. The
      coordinators were recruited with the assistance of the Ontario Telemedicine
      Network (OTN) and the Canadian Telehealth Forum (CTF). The response rate to the
      online survey from the OTN cohort was 4% (n = 13) and from the CTF cohort was 36%
      (n = 34). Of the 47 people who completed the survey, 16 also participated in a
      telephone interview. Most respondents were female; their mean age was 40 years.
      Most telehealth coordinators had some form of post-secondary education. Most, 66%
      (n = 31) coordinated both clinical and educational videoconferences. About half
      of the telehealth coordinators (55%, n = 26) indicated that their job was
      dedicated solely to telehealth, although 32% (n = 15) reported that their jobs
      involved responsibilities outside telehealth. About half of the respondents
      worked full-time (51%, n = 24). Most respondents either strongly agreed or agreed
      with the statement that 'If a telehealth coordinator's role involves patient care
      then that individual should be a member of a regulated health profession'. The
      need for organizations to more clearly define the role, better recognize and
      support telehealth coordinators and develop mechanisms for continuing
      professional education and certification were recurrent themes in the interviews.

PMID- 22604448
TI  - Epidemiological characteristics and genetic structure of blaNDM-1 in non
      baumannii Acinetobacter spp. in China.
AB  - OBJECTIVES: The goal of this study was to investigate the epidemiological
      characteristics and the surrounding genetic structure of bla(NDM-1) in non
      baumannii Acinetobacter spp. in China. METHODS: Non-baumannii Acinetobacter spp.
      were collected from 28 provinces in China and were screened for the presence of
      bla(NDM-1) using PCR. The following four methods were used to classify the
      Acinetobacter isolates: the Vitek 2 system, 16S-23S rRNA gene intergenic spacer
      sequencing, amplified rDNA restriction analysis and partial rpoB sequence
      analysis. An S1-PFGE assay and Southern blot hybridization were performed to
      determine the plasmid location of bla(NDM-1). The transferability of bla(NDM-1)
      harbouring plasmids was confirmed by conjugation experiments and
      electrotransformation. The surrounding genetic structure of the bla(NDM-1) gene
      was analysed using a restriction endonuclease-based cloning approach and primer
      walking. RESULTS: Among 726 non-baumannii Acinetobacter spp., nine isolates
      collected from six different provinces and assigned to seven different
      Acinetobacter spp. contained the bla(NDM-1) gene. None of these isolates was
      directly infectious to the patients or demonstrated an epidemiological
      importation from abroad. These bla(NDM-1) genes were located on plasmids that
      could be transferred to Escherichia coli J53 by conjugation and Acinetobacter
      baylyi ADP1 by electrotransformation. Seven of the nine strains shared a common
      genetic structure in which bla(NDM-1) was flanked by two copies of ISAba125.
      CONCLUSIONS: The clinical challenge posed by bla(NDM-1) is currently minimal in
      China; however, more attention should be devoted to monitoring the dissemination
      of this gene due to its potential transferability via the ISAba125-associated
      transposon.

PMID- 22604449
TI  - The ticking time bomb: escalating antibiotic resistance in Neisseria gonorrhoeae
      is a public health disaster in waiting.
AB  - From a once easily treatable infection, gonorrhoea has evolved into a challenging
      disease, which in future may become untreatable in certain circumstances.
      International spread of extensively drug-resistant gonococci would have severe
      public health implications. It seems clear that under the current treatment
      pressure from extended-spectrum cephalosporins, and owing to Neisseria
      gonorrhoeae's remarkable evolutionary adaptability, further rise of ceftriaxone
      resistant strains around the world is inevitable. Simply increasing the doses of
      extended-spectrum cephalosporins will likely prove ineffective in the long run,
      and has been a lesson learnt for all single-agent therapies used for gonorrhoea
      to date. We recommend that dual therapy, especially those consisting of extended
      spectrum cephalosporins and azithromycin, be adopted more widely and complemented
      by strengthening of antimicrobial resistance surveillance. Unless there is urgent
      action at international and local levels to combat the problem of N. gonorrhoeae
      antimicrobial resistance, we are in for gloomy times ahead in terms of gonorrhoea
      disease and control.

PMID- 22604450
TI  - Evaluation of a DNA microarray for the rapid detection of extended-spectrum beta
      lactamases (TEM, SHV and CTX-M), plasmid-mediated cephalosporinases (CMY-2-like,
      DHA, FOX, ACC-1, ACT/MIR and CMY-1-like/MOX) and carbapenemases (KPC, OXA-48,
      VIM, IMP and NDM).
AB  - OBJECTIVES: Carbapenem-resistant Gram-negative bacilli are reported increasingly
      and represent an emerging public health concern. Laboratory detection of extended
      spectrum beta-lactamase (ESBL), plasmid-mediated cephalosporinase (pAmpC) and
      carbapenemase producers remains a challenge for microbiology laboratories and is
      important to avoid clinical failure due to inappropriate antimicrobial therapy
      and to prevent nosocomial outbreaks. We evaluated a novel microarray, the 'Check
      MDR CT103 array' test (Check-Points, Wageningen, The Netherlands), that employs
      highly specific DNA markers to identify the beta-lactamase genes of ESBLs (TEM,
      SHV and CTX-M, and discriminates between ESBL and non-ESBL TEM and SHV variants),
      of pAmpC (CMY-2-like, DHA, FOX, ACC-1, ACT/MIR and CMY-1-like/MOX) and of
      carbapenemases (KPC, OXA-48, VIM, IMP and NDM). METHODS: One-hundred-and-eighty
      seven well-characterized Gram-negative bacilli isolates possessing different bla
      genes were tested. Total DNAs were extracted using a Qiagen DNA mini kit. The
      'Check-MDR CT103 array' was used as recommended by the manufacturer. RESULTS: The
      system correctly identified representatives of the three ESBL gene families
      tested, including differentiation between non-ESBL and ESBL TEM and SHV variants.
      All bla(CTX-M) genes were classified into the appropriate family group (i.e. CTX
      M-1 group, CTX-M-2 group, CTX-M-9 group and CTX-M-8/25/26 group). In addition,
      the clinically relevant plasmid-encoded cephalosporinase and carbapenemase genes
      were also reliably detected. Specificities and sensitivities of 100% were
      recorded for most bla genes. CONCLUSIONS: The 'Check-MDR CT103 array' is a
      powerful high-throughput tool for rapid identification of ESBL, pAmpC and
      carbapenemase producers in culture. Because of its rapid performance, this
      platform is a valuable tool for epidemiological or infection control studies.

PMID- 22604512
TI  - Burns in children: the importance of assessing for non-accidental injuries.
AB  - Children represent 30% of all burn cases seen by accident and emergency
      physicians in the UK every year, with toddlers being most at risk within this age
      group. With the emergence of walking autonomy, the need for constant supervision
      is sometimes not enough to prevent this type of injury from happening. However,
      in remembering the importance of children's health and safety, non-accidental
      injury is always to remain a differential diagnosis. The authors review a
      paediatric burns case underlying the importance of keeping an open mind to allow
      a proper clinical diagnosis to be formed.

PMID- 22604513
TI  - An infant with caudal appendage.
AB  - There are several human atavisms that reflect our common genetic heritage with
      other mammals. One of the most striking is the existence of the rare 'true human
      tail'. It is a rare event with fewer than 40 cases reported in the literature.
      The authors report a case of an infant born with the true tail. A 3-month-old
      baby girl, presented with an 11 cm long tail, which was successfully surgically
      removed. Human embryos normally have a prenatal tail, which disappears in the
      course of embryogenesis by programmed cell death. Recent advances in genetic
      research reveal that 'of those organs lost, in evolution, most species carry
      'genetic blue prints'. Thus, rarely the appearance of ancient organs like tail
      may be the result of re-expression of these switched off gene.

PMID- 22604514
TI  - Status of memory loss.
AB  - A 72-year-old woman presented with first onset of seizure with no prior history
      of cognitive dysfunction. EEG revealed focal non-convulsive status epilepticus.
      MRI brain showed a left temporal non-enhancing lesion. Temporal pole biopsy
      showed acute neuronal necrosis and astrocyte hyperplasia together with extensive
      amyloid plaques and neurofibrillary tangles. Perivascular oligodendroglial
      hyperplasia was present. Postmortem examination revealed extensive plaque and
      tangle disease. Perivascular oligodendroglial hyperplasia was limited to the left
      temporal area. The presence of focal perivascular oligodendroglial hyperplasia in
      the left temporal cortex, combined with extensive plaque and tangle disease may
      have contributed to the focal status epilepticus in this patient. Although the
      presence of focal perivascular oligodendroglial hyperplasia has been reported in
      cases of temporal lobe epilepsy, it has not been reported as a cause of seizure
      in patients with Alzheimer's disease previously. Further studies for clinical
      pathologic correlation would be required to confirm this hypothesis.

PMID- 22604515
TI  - Fat embolism syndrome in a child with dystonia musculorum deformans.
AB  - A 16-year-old boy with dystonia musculorum deformans underwent an operation for
      removal of femoral implants and excision of the prominence at the greater
      trochanter of the left hip. He was found to have fat embolism syndrome at
      postoperative day 1 as evidenced by confusion, respiratory symptoms, chest
      radiograph changes, raised erythrocyte sedimentation rate, thrombocytopenia and
      fat in the urine and sputum.

PMID- 22604576
TI  - Midterm outcomes of laparoscopic surgery for rectal cancer.
AB  - In this study, the authors examine midterm survival and recurrence after
      laparoscopic and open surgery for rectal cancer. This is a retrospective review
      of a prospective database for rectal cancer surgeries performed at the authors'
      institution, with follow-up data obtained through chart review. In all, 74
      patients in this study had open surgery, and 93 had laparoscopic surgery. The 5
      year overall survival was 73.6% +/- 12.0% in the open group and 80.0% +/- 12.8%
      in the laparoscopic group (P = .159). Disease-free survival at 5 years was better
      in the laparoscopic group (71.0% +/- 13.4%) than in the open group (50.3% +/-
      12.7%), with a P value of .01. Laparoscopic surgery remained an independent
      predictor of disease-free survival in the multivariate analysis. Results of
      prospective randomized trials are awaited, and the authors expect that the
      laparoscopic approach will be shown to be a safe and effective option for the
      management of rectal cancer.

PMID- 22604577
TI  - Transaxillary approach with use of traction suture for excision of breast
      fibroadenoma: a new technique and its results.
AB  - Avoiding a scar on the breast is an inherent feminine desire. We devised a new
      approach for breast fibroadenoma excision:Transaxillary approach with use of
      traction suture (TATS), in 50 patients with breast fibroadenoma. The swelling was
      present in the outer breast. The wound healed without noticeable scarring and the
      original shape of the breast was preserved. All the patients expressed their
      great satisfaction with the procedure.

PMID- 22604628
TI  - A simplified approach to assessing penile endothelial function in young
      individuals at risk of erectile dysfunction.
AB  - Erectile dysfunction (ED) reflects a risk for systemic cardiovascular  diseases
      by virtue of a common etiology of vascular endothelial dysfunction,  which is
      increasingly reported to affect young adults. On the basis of  physiological
      phenomenon of reactive hyperemia (RH), systemic and penile  endothelial functions
      in healthy young adults were compared with the use of  digital data on arterial
      waveforms before and after RH induction. Between July  2009 and March 2011, 32
      young adult volunteers with normal erectile functions  were recruited.
      Questionnaires on medical histories and sexual functions and  blood samples for
      testosterone and biochemical analyses were obtained.  Dilatation index (DI) and
      penile arterial waveform amplitude (PAWA) ratios for  assessing systemic and
      penile endothelial function were acquired with an air  pressure sensing system on
      the arm and a penile arterial waveform analyzing  system on the penis,
      respectively. A total cholesterol/high-density  lipoprotein (TC/HDL) ratio
      greater than 4.1 was used to define high risk for  ED. Remarkable positive
      correlation was noted between DI and PAWA ratio  (r = .640, P < .001). DI showed
      significant positive  associations with serum testosterone (P = .012) and serum
      HDL level,  whereas it showed negative correlations with total triglyceride and 
      glycosylated hemoglobulin levels, body weight, waist circumference, body mass 
      index, and diastolic blood pressure. Similarly, the PAWA ratio showed 
      significant positive correlations with serum testosterone (P <  .001) and HDL
      levels, but negative associations with body weight, waist  circumference, and
      body mass index. Both DI and PAWA ratio successfully  identified participants at
      high risk for ED (eg, TC/HDL ratio > 4.1;  P < .05). Our results demonstrated
      that penile endothelial  function can be assessed by evaluating systemic
      endothelial function in young  healthy adults for early identification of risk
      for ED.

PMID- 22604627
TI  - Association between sex steroid hormones and hematocrit in a nationally
      representative sample of men.
AB  - Low or high hematocrit levels are associated with increased morbidity and
      mortality, mediated via anemia or thromboembolic events, respectively. It is
      therefore important to identify factors that influence hematocrit. Although
      androgens are known to stimulate hematopoietic cells, it is unknown whether
      circulating sex steroid hormones affect hematocrit. The association between serum
      sex steroid hormone concentrations and hematocrit in men aged >= 20 years was
      evaluated in a cross-sectional study of 1273 men in the Third National Health and
      Nutrition Examination Survey (1988-1991). Outcomes were low (<10th percentile),
      high (>90th percentile), and mean hematocrit. Men with low free testosterone
      levels had a lower hematocrit than men with normal free testosterone levels (P =
      .03), although no relationship was found between total testosterone level and
      hematocrit. The relationship between sex hormone-binding globulin (SHBG) and
      hematocrit was complex, with both low (P < .001) and high (P = .01) SHBG levels
      associated with lower hematocrit in men aged >= 20 years and only high (P = .01)
      SHBG levels in men aged >= 50 years. The odds ratio (OR) of high vs normal
      hematocrit increased as total estradiol (OR, 2.84; P trend = .04) and free
      estradiol (OR, 2.23; P trend = .09) levels increased. In this nationally
      representative study of men, sex steroid hormone levels, particularly low free
      testosterone and high SHBG levels, were associated with lower hematocrit, and
      high total and free estradiol levels were associated with high hematocrit. Thus,
      changes in sex hormone levels with aging may contribute to the increased
      prevalence of anemia and thromboembolic stroke in men as they age.

PMID- 22604629
TI  - Free nerve ending density on skin extracted by circumcision and its relation to
      premature ejaculation.
AB  - Many studies have shown that skin tissue extracted by circumcision can  cause
      differences in sexual function, especially at the time of ejaculation. 
      Sensitivity changes in penile skin and sexual satisfaction deriving from 
      circumcision starting from premature ejaculation (PE) are discussed. 
      Furthermore, most of these studies rely on questionnaires. Extracted free  nerve
      endings (FNE) on the foreskin, which can detect temperature, mechanical  stimuli
      (touch, pressure, stretch) or pain (nociception), have not been  researched. Our
      aim is to determine FNEs in foreskin and the affects on sexual  function,
      especially PE. This prospective study was done on adults who  voluntarily applied
      to be circumcised between September 2010 and October 2011.  The ejaculation
      latency times (ELT) before circumcision have been assessed,  and a PE diagnostic
      tool (PEDT) form was filled out by the urologist according  to the answers given
      by the volunteers. The proximal and distal ends of the  foreskin were marked
      before circumcision, and the extracted foreskin was sent  to the pathology
      department to determine FNEs. Twenty volunteers (average age  21.25 +/- 0.44
      years) were included in the study. The average ELT was  103.55 +/- 68.39 seconds,
      and the average PE score was 4.35 +/-  3.13. Proximal, middle, and distal tip
      nerve densities were compared. Proximal  and distal (P = .003) and proximal and
      middle (P = .011)  segments differed from each other, whereas middle and distal
      were similar  (P = .119). There were not any correlations between PEDT scores and
      total nerve endings number (r = .018, P = .942). Also there  were not any
      correlations between mean ELT and PEDT scores (r = .054,  P = .822). The tissue
      extracted by circumcision has intensive FNEs,  yet FNE intensity has no relation
      to PE.

PMID- 22604658
TI  - INDEX TO ADVERTISERS.

PMID- 22604630
TI  - Penile veins are the principal component in erectile rigidity: a study of penile
      venous stripping on defrosted human cadavers.
AB  - The human erectile mechanism is an intricate interplay of hormonal,  vascular,
      neurological, sinusoidal, pharmacological, and psychological  factors. However,
      the relative influence of each respective component remains  somewhat unclear,
      and merits further study. We investigated the role of venous  outflow in an
      attempt to isolate the key determinant of erectile function.  Dynamic infusion
      cavernosometry and cavernosography was conducted on 15  defrosted human cadavers,
      both before and after the systematic removal and  ligation of erection-related
      penile veins. Preoperatively, an infusion rate of  more than 28.1 mL/min (from
      more than 14.0 to 85.0 mL/min) was required to  induce a rigid erection (defined
      as intracavernosal pressure [ICP] exceeding  90 mmHg). Following surgery, we were
      able to obtain the same result at a rate  of 7.3 mL/min (from 3.1 to 13.5 mL/min)
      across the entire sample. Thus, we  witnessed statistically significant
      postoperative differences (all P  <= .01), consistently elevated ICP, lower
      perfusion volumes, and a general  reduction in time taken to attain rigidity. The
      cavernosograms provided  further evidence substantiating the critical role played
      by erection-related  veins, whereas histological samples confirmed the
      postoperative integrity of  the corpora cavernosa. Given that our use of cadavers
      eliminated the influence  of hormonal, arterial, neurological, sinusoidal,
      pharmacological, and  psychological factors, we believe that our study
      demonstrates that the human  erection is fundamentally a mechanical event
      contingent on venous  competence.

PMID- 22604659
TI  - Picture of the Month.
AB  - A 21/2year-old boy had the onset of pain and swelling of his penis during the
      past 3 days. The swelling and pain increased significantly within the past 24
      hours. The child's penis is shown in the Figure. DENOUEMENT AND DISCUSSION 
      PARAPHIMOSIS Paraphimosis is an urologic emergency that results when the foreskin
      is retracted away from the glans penis and cannot be reduced to its former
      position. The opening in the prepuce, when forcibly retracted beyond the coronal
      sulcus, becomes a constricting ring that cannot be reduced. The constricting ring
      created causes a tension greater than the lymphatic pressure and results in edema
      of the prepuce, the penile shaft, and the glans penis distal to the incarcerated
      foreskin.1,2As lymphatic drainage is impaired and tissue swelling increases,
      reduction of the foreskin becomes more difficult. Pain occurs as a result of
      swelling, and, eventually, as a result of vascular compromise. If.

PMID- 22604660
TI  - Infant Growth Differs by Feeding Mode-Reply.
AB  - Dr Basco refers to the NCHS infant growth curves as "standards." Although many
      users view these curves as standards, and communicate as such to parents, we
      deliberately avoided using that term. Drs Frongillo and Garza succinctly review
      the significance of the use of growth references as "standards."Dr Basco
      requested more information about feeding practices of the cohorts. For the
      Pediatric Practice Research Group (PPRG) cohort, information about infant diet
      was collected from parents at each visit. Fifty-six percent of the infants in the
      PPRG curves were at least partially breast-fed for 1 month and 40% for 6 months.1
      This closely approximates the rates of breast-feeding reported in national
      surveys during that period.2 Most infants included in the NCHS curves were
      formula-fed; greater detail is unavailable.Choosing the reference cohort for
      infant growth based on a concern for obesity is unfounded. It has been shown that
      the predictive.

PMID- 22604661
TI  - Nelson Textbook of Pediatrics.
AB  - The dedication of this volume states:To the physicians and nurses who care for
      children in many different circumstances throughout the world and who, by their
      efforts and commitment, make the world a better place for children.I have used
      the Nelson Textbook of Pediatrics since its third edition. It remains a source of
      amazement to me, as I witness the evolution of the book and of the knowledge that
      dictates its scope. From the days when a textbook was written by 1 or 2 authors,
      we have progressed to the point where this would be impossible. Three editors
      preside over this volume; they are also counted among the 212 contributors that
      lend special expertise to the work, continuing the volume as one of the
      traditions of pediatrics.The tremendous and rapid explosion in the amount of
      knowledge in pediatrics made a revision of the total material and even of.

PMID- 22604662
TI  - The Monkey-Rope: A Psychotherapist's Reflections on Relationships.
AB  - Jerry Lewis is a psychiatrist who has devoted the better part of his career to
      studying families and promoting a consideration of families in mental health
      practice. He has written this book, a series of 40 brief essays, for the lay
      reader. These essays are the reflections of a professional who has experience in
      caring for patients, conducting research, and teaching medical students and house
      officers. Dr Lewis attempts to present ideas and information about how
      relationships are associated with adjustment and well-being or hardships.In the
      Epilogue, Dr Lewis notes that publishers warned him that the lay readership wants
      answers and certainty. In his essays, he presents possibilities, several possible
      contributing factors to the conditions that are being described, balancing
      biological and classical psychodynamic concerns with the interpersonal angle.In
      the first half of the book, different aspects of self-description, or self
      knowledge, are described. For example, Dr Lewis presents.

PMID- 22604663
TI  - Physician Recruitment.

PMID- 22604720
TI  - Evolution and functional impact of rare coding variation from deep sequencing of
      human exomes.
AB  - As a first step toward understanding how rare variants contribute to risk for
      complex diseases, we sequenced 15,585 human protein-coding genes to an average
      median depth of 111* in 2440 individuals of European (n = 1351) and African (n =
      1088) ancestry. We identified over 500,000 single-nucleotide variants (SNVs), the
      majority of which were rare (86% with a minor allele frequency less than 0.5%),
      previously unknown (82%), and population-specific (82%). On average, 2.3% of the
      13,595 SNVs each person carried were predicted to affect protein function of ~313
      genes per genome, and ~95.7% of SNVs predicted to be functionally important were
      rare. This excess of rare functional variants is due to the combined effects of
      explosive, recent accelerated population growth and weak purifying selection.
      Furthermore, we show that large sample sizes will be required to associate rare
      variants with complex traits.

PMID- 22604721
TI  - Planetary science. Fragments of the lunar cataclysm.

PMID- 22604723
TI  - Graphene barristor, a triode device with a gate-controlled Schottky barrier.
AB  - Despite several years of research into graphene electronics, sufficient on/off
      current ratio I(on)/I(off) in graphene transistors with conventional device
      structures has been impossible to obtain. We report on a three-terminal active
      device, a graphene variable-barrier "barristor" (GB), in which the key is an
      atomically sharp interface between graphene and hydrogenated silicon. Large
      modulation on the device current (on/off ratio of 10(5)) is achieved by adjusting
      the gate voltage to control the graphene-silicon Schottky barrier. The absence of
      Fermi-level pinning at the interface allows the barrier's height to be tuned to
      0.2 electron volt by adjusting graphene's work function, which results in large
      shifts of diode threshold voltages. Fabricating GBs on respective 150-mm wafers
      and combining complementary p- and n-type GBs, we demonstrate inverter and half
      adder logic circuits.

PMID- 22604722
TI  - An abundance of rare functional variants in 202 drug target genes sequenced in
      14,002 people.
AB  - Rare genetic variants contribute to complex disease risk; however, the abundance
      of rare variants in human populations remains unknown. We explored this spectrum
      of variation by sequencing 202 genes encoding drug targets in 14,002 individuals.
      We find rare variants are abundant (1 every 17 bases) and geographically
      localized, so that even with large sample sizes, rare variant catalogs will be
      largely incomplete. We used the observed patterns of variation to estimate
      population growth parameters, the proportion of variants in a given frequency
      class that are putatively deleterious, and mutation rates for each gene. We
      conclude that because of rapid population growth and weak purifying selection,
      human populations harbor an abundance of rare variants, many of which are
      deleterious and have relevance to understanding disease risk.

PMID- 22604724
TI  - Roton-type mode softening in a quantum gas with cavity-mediated long-range
      interactions.
AB  - Long-range interactions in quantum gases are predicted to give rise to an
      excitation spectrum of roton character, similar to that observed in superfluid
      helium. We investigated the excitation spectrum of a Bose-Einstein condensate
      with cavity-mediated long-range interactions, which couple all particles to each
      other. Increasing the strength of the interaction leads to a softening of an
      excitation mode at a finite momentum, preceding a superfluid-to-supersolid phase
      transition. We used a variant of Bragg spectroscopy to study the mode softening
      across the phase transition. The measured spectrum was in very good agreement
      with ab initio calculations and, at the phase transition, a diverging
      susceptibility was observed. The work paves the way toward quantum simulation of
      long-range interacting many-body systems.

PMID- 22604725
TI  - Direct detection of projectile relics from the end of the lunar basin-forming
      epoch.
AB  - The lunar surface, a key proxy for the early Earth, contains relics of asteroids
      and comets that have pummeled terrestrial planetary surfaces. Surviving fragments
      of projectiles in the lunar regolith provide a direct measure of the types and
      thus the sources of exogenous material delivered to the Earth-Moon system. In
      ancient [>3.4 billion years ago (Ga)] regolith breccias from the Apollo 16
      landing site, we located mineral and lithologic relics of magnesian chondrules
      from chondritic impactors. These ancient impactor fragments are not nearly as
      diverse as those found in younger (3.4 Ga to today) regolith breccias and soils
      from the Moon or that presently fall as meteorites to Earth. This suggests that
      primitive chondritic asteroids, originating from a similar source region, were
      common Earth-Moon-crossing impactors during the latter stages of the basin
      forming epoch.

PMID- 22604761
TI  - Tuberculous mediastinal abscess as a paradoxical reaction in an immunocompetent
      individual.
AB  - A 22-year-old man, diagnosed 7 weeks before with pulmonary tuberculosis and
      started on antitubercular therapy, presented with non-exertional retrosternal
      chest pain since the past week. He was diagnosed on the strength of thoracic
      radiograms and CT imaging to have a mediastinal abscess, which was percutaneously
      drained. He was continued on the same regimen of drugs. Analysis of the fluid
      obtained was suggestive of tuberculous aetiology. Steroids were not required.

PMID- 22604726
TI  - Oscillatory dynamics of Cdc42 GTPase in the control of polarized growth.
AB  - Cells promote polarized growth by activation of Rho-family protein Cdc42 at the
      cell membrane. We combined experiments and modeling to study bipolar growth
      initiation in fission yeast. Concentrations of a fluorescent marker for active
      Cdc42, Cdc42 protein, Cdc42-activator Scd1, and scaffold protein Scd2 exhibited
      anticorrelated fluctuations and oscillations with a 5-minute average period at
      polarized cell tips. These dynamics indicate competition for active Cdc42 or its
      regulators and the presence of positive and delayed negative feedbacks. Cdc42
      oscillations and spatial distribution were sensitive to the amounts of Cdc42
      activator Gef1 and to the activity of Cdc42-dependent kinase Pak1, a negative
      regulator. Feedbacks regulating Cdc42 oscillations and spatial self-organization
      appear to provide a flexible mechanism for fission yeast cells to explore
      polarization states and to control their morphology.

PMID- 22604762
TI  - A 56-year-old woman with stress-induced hoarseness.
AB  - A 56-year-old woman was admitted to hospital due to stress-dependent hoarseness
      and hypertensive urgency. The patient reported peaks of blood pressure of 210/160
      mm Hg in combination with hoarseness. With indirect mirror examination, the ear
      nose-and throat doctor diagnosed a paralysis of the vocal cord on the left side.
      The authors suspected a mass affecting the vagus nerve and performed a CT-scan
      with iodinated contrast material of the neck and thorax. Surprisingly the CT-scan
      showed an aneurysm of the aortic arch with a dilatation up to 4.8 cm, a kinking
      of 120 degrees  and a chronic dissection in the aneurysm. During exercise or
      elevated blood pressure this aneurysm expanded and made a compression of the
      nervus laryngeus recurrens on the left side. Thus, there is an explanation for
      the patient's hoarseness on exertion and during hypertensive urgency.

PMID- 22604763
TI  - Late-presenting diaphragmatic hernia associated with intrathoracic kidney:
      tachypnoea as unique clinical sign.
AB  - Intrathoracic renal ectopia associated with a congenital diaphragmatic hernia
      represents a very rare congenital malformation. The incidence of intrathoracic
      renal ectopia with congenital diaphragmatic hernia is reported to be less than
      0.25%. The authors report on a 5-month-old female infant with late-presenting
      congenital diaphragmatic hernia associated with a left-sided intrathoracic
      ectopic kidney and adrenal gland. While prenatal ultrasound showed no pathology,
      the postnatal ultrasound assumed a left-sided renal agenesia. After recurrent
      episodes of tachypnoea, a chest x-ray confirmed the diagnosis of congenital
      diaphragmatic hernia which was repaired without complications. Intraoperatively,
      intrathoracic ectopic kidney was diagnosed. The authors discuss embryogenesis,
      the diagnostic algorithm and therapy as well as follow-up of this rare
      malformation.

PMID- 22604764
TI  - Unraveling the paradox of cardiac tamponade: case presentation and discussion of
      physiology.
AB  - A 53-year-old man on warfarin for postoperative pulmonary embolism presented with
      chest pain and was found to be in cardiac tamponade due to an atraumatic
      haemopericardium. Findings of tamponade and a novel approach to the
      pathophysiology of pericardial disease to explain these finding are presented.

PMID- 22604765
TI  - Oro-dental findings in Bardet-Biedl syndrome.
AB  - The Bardet-Biedl syndrome (BBS) is a human genetic disorder with an array of
      clinical features affecting many body systems. BBS is a pleiotropic disorder with
      mostly monogenic causes. It is also considered a primary ciliopathy syndrome. It
      is characterised by obesity, pigmentary retinopathy, polydactyly, mental
      deficiency and hypogonadism and recently a sixth feature, renal disease, has also
      been described. Since none of the diverse symptoms of BBS by itself is diagnostic
      of the disorder and many of the symptoms only become apparent over time,
      diagnosis of the BBS is often delayed until about 9 years of age when visual
      problems first appear.

PMID- 22604766
TI  - Use of once-weekly statin in combination with ezetimibe in a patient with
      mitochondrial disease.
AB  - The authors describe a patient with personal and family history of muscle pains
      highly suggestive of mitochondrial disease. She presented with familial combined
      hyperlipidaemia with family history of premature coronary artery disease. After 4
      week therapy of 5 mg of rosuvastatin once a week combined with 10 mg of ezetimibe
      daily, the low-density lipoprotein cholesterol level was markedly decreased from
      3.88 to 2.82 mmol/l (27.3% reduction). She has experienced no adverse effects
      after 6 month treatment. The results suggest that the combination therapy of low
      dose once-weekly rosuvastatin and daily ezetimibe could be used as an effective
      regimen for patients with mitochondrial disease.

PMID- 22604767
TI  - Acute hepatitis E virus infection and autoimmune thyroiditis: yet another
      trigger?
AB  - A middle aged woman, previously healthy with the exception of mild seasonal
      asthma was presented with signs of acute hepatitis. The further investigation
      showed acute hepatitis E virus infection associated with autoimmune thyroiditis.
      Treatment was started with propranolol and carbimazol whereupon hepatitis and
      hyperthyroidism resolved. The authors think that the observed association of
      acute hepatitis E virus infection and autoimmune thyroiditis suggests a role of
      hepatitis E virus as putative trigger of autoimmune thyroiditis. The alternative
      possibility of thyroid dysfunction due to pre-existing autoantibodies cannot be
      completely excluded but seems to be unlikely given the very mild course of
      seasonal asthma in this patient.

PMID- 22604768
TI  - Use of phentolamine in the treatment of Epipen induced digital ischaemia.
AB  - A 33-year-old lady accidentally injected norepinephrine into her right thumb
      while cleaning the first aid box where a spare Epipen for her son was kept. She
      presented with pain, pallor and swelling to the distal phalanx of the right
      thumb. After a prompt literature search and discussing the case with the National
      Poisons Information Service, local injection of 0.15 ml (1.5 mg) of phentolamine
      in 1 ml of 2% lignocaine was advised. Peripheral perfusion was restored
      immediately after injection and fully recovery was noted at the review clinic the
      following day. The presentation of this case in the accident and emergency
      department prompted phone calls and literature search to define the most
      appropriate evidence-based management for this situation. The authors conclude
      that local infiltration of phentolamine is the treatment of choice and this
      highlighted the need for local treatment protocols.

PMID- 22604769
TI  - Equine laryngeal rhinosporidiosis in western Canada.
AB  - A 12-year-old female Argentinean Warmblood mare was evaluated because of
      respiratory noise. The horse resided in Calgary, Alberta, Canada, but had been
      imported from Argentina 28 months prior to presentation. Endoscopy of the upper
      respiratory tract revealed a single polypoid mass on the left arytenoid. The mass
      was surgically excised and was diagnosed histologically as rhinosporidiosis.
      Polymerase chain reaction and DNA sequencing were used to confirm the etiological
      agent. Four weeks postoperatively, endoscopy was repeated, revealing recurrence
      of the original lesion with multiple additional polypoid masses on the larynx and
      in the oropharynx. Resolution of the disease had not been attained at the time of
      publication. The current report outlines a case of rhinosporidiosis in an unusual
      anatomical and geographic location. The infection most likely originated in
      Argentina, with a prolonged subclinical phase. Due to increased travel of human
      beings and animals, there is potential for the introduction of exotic diseases
      into nonendemic areas.

PMID- 22604770
TI  - Malignant peripheral nerve sheath tumor in a cat with nodal and pulmonary
      metastases.
AB  - Peripheral nerve sheath tumors in domestic cats are infrequently reported and are
      often locally invasive. An 11-year-old Domestic Shorthair cat was originally
      diagnosed with a right maxillary benign peripheral nerve sheath tumor at
      incisional biopsy. At necropsy, the neoplasm had features of malignancy including
      metastases to the regional lymph nodes and lung. Histologically, the neoplasm
      contained 2 distinct regions: spindle cells arranged in dense interwoven bundles
      with Antoni A areas and Verocay bodies and Antoni B regions with loosely arranged
      spindle cells separated by a mucinous matrix. Immunohistochemically, the
      neoplastic cells in the primary mass and right mandibular lymph node were
      strongly positive for vimentin, S-100, and glial fibrillar acidic protein. The
      neoplastic cells within the lung were strongly positive for vimentin and weakly
      positive for S-100 and glial fibrillar acidic protein.

PMID- 22604771
TI  - Investigation of a Microcystis aeruginosa cyanobacterial freshwater harmful algal
      bloom associated with acute microcystin toxicosis in a dog.
AB  - Microcystin poisoning was diagnosed in a dog exposed to a Microcystis aeruginosa
      dominated, freshwater, harmful algal bloom at Milford Lake, Kansas, which
      occurred during the summer of 2011. Lake water microcystin concentrations were
      determined at intervals during the summer, using competitive enzyme-linked
      immunosorbent assays, and indicated extremely high, localized microcystin
      concentrations of up to 126,000 ng/ml. Multiple extraction and analysis
      techniques were used in the determination of free and total microcystins in
      vomitus and liver samples from the poisoned dog. Vomitus and liver contained
      microcystins, as determined by enzyme-linked immunosorbent assays, and the
      presence of microcystin-LR was confirmed in vomitus and liver samples using
      liquid chromatography coupled with tandem mass spectrometry. Major toxic effects
      in a dog presented for treatment on the day following exposure included fulminant
      liver failure and coagulopathy. The patient deteriorated rapidly despite
      aggressive treatment and was euthanized. Postmortem lesions included diffuse,
      acute, massive hepatic necrosis and hemorrhage, as well as acute necrosis of the
      renal tubular epithelium. A diagnosis of microcystin poisoning was based on the
      demonstration of M. aeruginosa and microcystin-LR in the lake water, as well as
      in vomitus produced early in the course of the poisoning; the presence of
      microcystin-LR in liver tissue; and a typical clinical course including
      gastroenteritis and fulminant liver failure.

PMID- 22604772
TI  - Chondrosarcoma of the scapula of an 8-month-old Holstein steer.
AB  - Malignant neoplasms occur commonly in cattle, with lymphosarcoma being the most
      common. Chondrosarcoma rarely has been described and only in mature cattle. The
      present report describes a chondrosarcoma of the left scapula of an 8-month-old
      Holstein steer. Histologic examination of the mass revealed an unencapsulated,
      multilobular neoplasm composed of neoplastic spindle cells embedded in irregular
      islands of chondroid matrix, consistent with a diagnosis of chondrosarcoma.

PMID- 22604773
TI  - Molecular characterization of Canine minute virus associated with neonatal
      mortality in a litter of Jack Russell terrier dogs.
AB  - The molecular characterization of a strain of Canine minute virus (CnMV)
      associated with neonatal death is reported. Three newborn puppies of a litter of
      Jack Russell terrier dogs died after displaying systemic disease, whereas 2
      surviving puppies showed no clinical signs with the exception of transient
      cardiac abnormalities that were evident by electrocardiography. Necropsy of 1
      dead puppy revealed severe lesions in the internal organs. A strain of Canine
      minute virus was detected in tissue samples collected from the puppy, and virus
      circulation was demonstrated by molecular or serological testing in the dam,
      puppies of the same litter, and other puppies in the same kennel. By sequence and
      phylogenetic analysis of the gene encoding for the VP2 capsid protein, the strain
      circulating in the kennel was found to be related to recent Asian CnMV isolates.
      Continuous molecular surveillance for CnMV in kennels, shelters, and rescue
      centers would expand the knowledge base on the epidemiological and pathogenetic
      features of CnMV, which has been known for several decades but still poorly
      understood.

PMID- 22604860
TI  - Effect of heparin-derived oligosaccharide on vascular smooth muscle cell
      proliferation.
AB  - In this study, the effect of heparin-derived oligosaccharide on bovine vascular
      smooth muscle cell (VSMC) proliferation and signal transduction mechanism was
      investigated. Extracellular-signal-regulated kinase (ERK) 1/2 has been implicated
      in the regulation of various cellular functions including proliferation, and we
      sought to define a functional role for ERK 1/2 in an established proliferation
      model in order to find a possible mechanism for inhibition of VSMC proliferation
      by heparin-derived oligosaccharide. The VSMC proliferation model was developed by
      platelet-derived growth factor (PDGF), and the level of ERK 1/2 protein and
      messenger RNA was determined by reverse transcriptase-polymerase chain reaction,
      Western blotting, and immunocytochemical methods. Flow cytometry analysis
      indicated that heparin-derived oligosaccharide blocked PDGF-induced cell cycle
      progression by arresting cells in the G0/G1 phase. The results imply that heparin
      derived oligosaccharide inhibits VSMC proliferation by moderating the gene and
      the phosphorylation levels of ERK 1/2, eventually blocking G1/S transition, may
      be one of the mechanisms for inhibition of VSMC proliferation by heparin-derived
      oligosaccharide.

PMID- 22604774
TI  - Diagnosis of Porcine teschovirus encephalomyelitis in the Republic of Haiti.
AB  - In February and March 2009, approximately 1,500 backyard pigs of variable age
      became sick, and approximately 700 of them died or were euthanized in the Lower
      Artibonite Valley and the Lower Plateau of the Republic of Haiti. The main
      clinical sign was posterior ataxia followed by paresis and/or paralysis on the
      second or third day of illness. No gross lesions were observed at postmortem
      examinations. The morbidity and mortality were approximately 60% and 40%,
      respectively. Diagnostic samples (whole blood, brain, tonsil, lymph nodes,
      spleen, and lung) were negative for Classical swine fever virus and African swine
      fever virus. Porcine teschovirus type 1 was detected by reverse transcription
      polymerase chain reactions in brain samples. Results of virus isolation, electron
      microscopy of virus particles, histopathological analysis on brain tissues,
      nucleic acid sequencing, and phylogenetic analysis of the viral isolate supported
      the diagnosis of teschovirus encephalomyelitis. The outbreak of the disease in
      Haiti is the first appearance of the severe form of teschovirus encephalomyelitis
      in the Americas. This disease poses a potential threat to the swine industries in
      other Caribbean countries, as well as to Central and North American countries.

PMID- 22604882
TI  - Effect of menstrual cycle phase on the ventilatory response to rising body
      temperature during exercise.
AB  - To examine the effect of menstrual cycle on the ventilatory sensitivity to rising
      body temperature, ten healthy women exercised for ~60 min on a cycle ergometer at
      50% of peak oxygen uptake during the follicular and luteal phases of their cycle.
      Esophageal temperature, mean skin temperature, mean body temperature, minute
      ventilation, and tidal volume were all significantly higher at baseline and
      during exercise in the luteal phase than the follicular phase. On the other hand,
      end-tidal partial pressure of carbon dioxide was significantly lower during
      exercise in the luteal phase than the follicular phase. Plotting ventilatory
      parameters against esophageal temperature revealed there to be no significant
      menstrual cycle-related differences in the slopes or intercepts of the regression
      lines, although minute ventilation and tidal volume did significantly differ
      during exercise with mild hyperthermia. To evaluate the cutaneous vasodilatory
      response, relative laser-Doppler flowmetry values were plotted against mean body
      temperature, which revealed that the mean body temperature threshold for
      cutaneous vasodilation was significantly higher in the luteal phase than the
      follicular phase, but there were no significant differences in the sensitivity or
      peak values. These results suggest that the menstrual cycle phase influences the
      cutaneous vasodilatory response during exercise and the ventilatory response at
      rest and during exercise with mild hyperthermia, but it does not influence
      ventilatory responses during exercise with moderate hyperthermia.

PMID- 22604883
TI  - Quadriceps neuromuscular function and self-reported functional ability in knee
      osteoarthritis.
AB  - The purposes of this study were to determine 1) the relationships of self
      reported function scores in patients with knee osteoarthritis (OA) to both
      maximal isometric torque and to isotonic power at a variety of loads, and 2) the
      degree to which muscle volume (MV) or voluntary activation (VA) are associated
      with torque and power measures in this population. Isometric maximal voluntary
      contraction (MVC) torque and isotonic power [performed at loads corresponding to
      10, 20, 30, 40, and 50% MVC, and a minimal load ("Zero Load")] were measured in
      40 participants with knee OA. Functional ability was measured with the Western
      Ontario and McMaster Osteoarthritis Index (WOMAC) function subscale. MV was
      determined with magnetic resonance imaging, and VA was measured with the
      interpolated twitch technique. In general, power measured at lower loads (Zero
      Load and 10-30% MVC, r(2) = 0.21-0.28, P < 0.05) predicted a greater proportion
      of the variance in function than MVC torque (r(2) = 0.18, P < 0.05), with power
      measured at Zero Load showing the strongest association (r(2) = 0. 28, P < 0.05).
      MV was the strongest predictor of MVC torque and power measures in multiple
      regression models (r(2) = 0.42-0.72). VA explained only 6% of the variance in MVC
      torque and was not significantly associated with power at any load (P > 0.05).
      Quadriceps MVC torque and power are associated with self-reported function in
      knee OA, but muscle power at lower loads is more predictive of function than MVC
      torque. The variance in MVC torque and power between participants is due
      predominantly to differences in MV and has little to do with deficits in VA.

PMID- 22604885
TI  - Inert gas clearance from tissue by co-currently and counter-currently arranged
      microvessels.
AB  - To elucidate the clearance of dissolved inert gas from tissues, we have developed
      numerical models of gas transport in a cylindrical block of tissue supplied by
      one or two capillaries. With two capillaries, attention is given to the effects
      of co-current and counter-current flow on tissue gas clearance. Clearance by
      counter-current flow is compared with clearance by a single capillary or by two
      co-currently arranged capillaries. Effects of the blood velocity, solubility, and
      diffusivity of the gas in the tissue are investigated using parameters with
      physiological values. It is found that under the conditions investigated, almost
      identical clearances are achieved by a single capillary as by a co-current pair
      when the total flow per tissue volume in each unit is the same (i.e., flow
      velocity in the single capillary is twice that in each co-current vessel). For
      both co-current and counter-current arrangements, approximate linear relations
      exist between the tissue gas clearance rate and tissue blood perfusion rate.
      However, the counter-current arrangement of capillaries results in less-efficient
      clearance of the inert gas from tissues. Furthermore, this difference in
      efficiency increases at higher blood flow rates. At a given blood flow, the
      simple conduction-capacitance model, which has been used to estimate tissue blood
      perfusion rate from inert gas clearance, underestimates gas clearance rates
      predicted by the numerical models for single vessel or for two vessels with co
      current flow. This difference is accounted for in discussion, which also
      considers the choice of parameters and possible effects of microvascular
      architecture on the interpretation of tissue inert gas clearance.

PMID- 22604886
TI  - Imaging regional PAO2 and gas exchange.
AB  - Several methods allow regional gas exchange to be inferred from imaging of
      regional ventilation and perfusion (V/Q) ratios. Each method measures slightly
      different aspects of gas exchange and has inherent advantages and drawbacks that
      are reviewed. Single photon emission computed tomography can provide regional
      measure of ventilation and perfusion from which regional V/Q ratios can be
      derived. PET methods using inhaled or intravenously administered nitrogen-13
      provide imaging of both regional blood flow, shunt, and ventilation. Electric
      impedance tomography has recently been refined to allow simultaneous measurements
      of both regional ventilation and blood flow. MRI methods utilizing hyperpolarized
      helium-3 or xenon-129 are currently being refined and have been used to estimate
      local PaO(2) in both humans and animals. Microsphere methods are included in this
      review as they provide measurements of regional ventilation and perfusion in
      animals. One of their advantages is their greater spatial resolution than most
      imaging methods and the ability to use them as gold standards against which new
      imaging methods can be tested. In general, the reviewed methods differ in
      characteristics such as spatial resolution, possibility of repeated measurements,
      radiation exposure, availability, expensiveness, and their current stage of
      development.

PMID- 22604884
TI  - Imaging lung perfusion.
AB  - From the first measurements of the distribution of pulmonary blood flow using
      radioactive tracers by West and colleagues (J Clin Invest 40: 1-12, 1961)
      allowing gravitational differences in pulmonary blood flow to be described, the
      imaging of pulmonary blood flow has made considerable progress. The researcher
      employing modern imaging techniques now has the choice of several techniques,
      including magnetic resonance imaging (MRI), computerized tomography (CT),
      positron emission tomography (PET), and single photon emission computed
      tomography (SPECT). These techniques differ in several important ways: the
      resolution of the measurement, the type of contrast or tag used to image flow,
      and the amount of ionizing radiation associated with each measurement. In
      addition, the techniques vary in what is actually measured, whether it is
      capillary perfusion such as with PET and SPECT, or larger vessel information in
      addition to capillary perfusion such as with MRI and CT. Combined, these issues
      affect quantification and interpretation of data as well as the type of
      experiments possible using different techniques. The goal of this review is to
      give an overview of the techniques most commonly in use for physiological
      experiments along with the issues unique to each technique.

PMID- 22604887
TI  - Exercise modulation of the host-tumor interaction in an orthotopic model of
      murine prostate cancer.
AB  - The purpose of this study is to investigate the effects of exercise on cancer
      progression, metastasis, and underlying mechanisms in an orthotopic model of
      murine prostate cancer. C57BL/6 male mice (6-8 wk of age) were orthotopically
      injected with transgenic adenocarcinoma of mouse prostate C-1 cells (5 * 10(5))
      and randomly assigned to exercise (n = 28) or a non-intervention control (n = 31)
      groups. The exercise group was given voluntary access to a wheel 24 h/day for the
      duration of the study. Four mice per group were serially killed on days 14, 31,
      and 36; the remaining 38 mice (exercise, n = 18; control, n = 20) were killed on
      day 53. Before death, MRI was performed to assess tumor blood perfusion. Primary
      tumor growth rate was comparable between groups, but expression of prometastatic
      genes was significantly modulated in exercising animals with a shift toward
      reduced metastasis. Exercise was associated with increased activity of protein
      kinases within the MEK/MAPK and PI3K/mTOR signaling cascades with subsequent
      increased intratumoral protein levels of HIF-1alpha and VEGF. This was associated
      with improved tumor vascularization. Multiplex ELISAs revealed distinct
      reductions in plasma concentrations of several angiogenic cytokines in the
      exercise group, which was associated with increased expression of angiogenic and
      metabolic genes in the skeletal muscle. Exercise-induced stabilization of HIF
      1alpha and subsequent upregulation of VEGF was associated with "productive" tumor
      vascularization with a shift toward suppressed metastasis in an orthotopic model
      of prostate cancer.

PMID- 22604888
TI  - An amino acid mixture is essential to optimize insulin-stimulated glucose uptake
      and GLUT4 translocation in perfused rodent hindlimb muscle.
AB  - The purpose of this study was to investigate whether an amino acid mixture
      increases glucose uptake across perfused rodent hindlimb muscle in the presence
      and absence of a submaximal insulin concentration, and if the increase in glucose
      uptake is related to an increase in GLUT4 plasma membrane density. Sprague-Dawley
      rats were separated into one of four treatment groups: basal, amino acid mixture,
      submaximal insulin, or amino acid mixture with submaximal insulin. Glucose uptake
      was greater for both insulin-stimulated treatments compared with the non-insulin
      stimulated treatment groups but amino acids only increased glucose uptake in the
      presence of insulin. Phosphatidylinositol 3-kinase (PI 3-kinase) activity was
      greater for both insulin-stimulated treatments with amino acids having no
      additional impact. Akt substrate of 160 kDa (AS160) phosphorylation, however, was
      increased by the amino acids in the presence of insulin, but not in the absence
      of insulin. AMPK was unaffected by insulin or amino acids. Plasma membrane GLUT4
      protein concentration was greater in the rats treated with insulin compared with
      no insulin in the perfusate. In the presence of insulin, amino acids increased
      GLUT4 density in the plasma membrane but had no effect in the absence of insulin.
      AS160 phosphorylation and plasma membrane GLUT4 density accounted for 76% of the
      variability in muscle glucose uptake. Collectively, these findings suggest that
      the beneficial effects of an amino acid mixture on skeletal muscle glucose
      uptake, in the presence of a submaximal insulin concentration, are due to an
      increase in AS160 phosphorylation and plasma membrane-associated GLUT4, but
      independent of PI 3-kinase and AMPK activation.

PMID- 22604889
TI  - Muscle metabolic status and acid-base balance during 10-s work:5-s recovery
      intermittent and continuous exercise.
AB  - Gastrocnemius muscle phosphocreatine ([PCr]) and hydrogen ion ([H(+)]) were
      measured using (31)P-magnetic resonance spectroscopy during repeated bouts of 10
      s heavy-intensity (HI) exercise and 5-s rest compared with continuous (CONT) HI
      exercise. Recreationally active male subjects (n = 7; 28 yr +/- 9 yr) performed
      on separate occasions 12 min of isotonic plantar flexion (0.75 Hz) CONT and
      intermittent (INT; 10-s exercise, 5-s rest) exercise. The HI power output in both
      CONT and INT was set at 50% of the difference between the power output associated
      with the onset of intracellular acidosis and peak exercise determined from a
      prior incremental plantar flexion protocol. Intracellular concentrations of [PCr]
      and [H(+)] were calculated at 4 s and 9 s of the work period and at 4 s of the
      rest period in INT and during CONT exercise. [PCr] and [H(+)] (mean +/- SE) were
      greater at 4 s of the rest periods vs. 9 s of exercise over the course of the INT
      exercise bout: [PCr] (20.7 mM +/- 0.6 vs. 18.7 mM +/- 0.5; P < 0.01); [H(+)] (370
      nM +/- 13.50 vs. 284 nM +/- 13.6; P < 0.05). Average [H(+)] was similar for CONT
      vs. INT. We therefore suggest that there is a glycolytic contribution to ATP
      recovery during the very short rest period (<5 s) of INT and that the greater
      average power output of CONT did not manifest in greater [H(+)] and greater
      glycolytic contribution compared with INT exercise.

PMID- 22604890
TI  - Comparison of various approaches to calculating the optimal hematocrit in
      vertebrates.
AB  - An interesting problem in hemorheology is to calculate that volume fraction of
      erythrocytes (hematocrit) that is optimal for transporting a maximum amount of
      oxygen. If the hematocrit is too low, too few erythrocytes are present to
      transport oxygen. If it is too high, the blood is very viscous and cannot flow
      quickly, so that oxygen supply to the tissues is again reduced. These
      considerations are very important, since oxygen transport is an important factor
      for physical performance. Here, we derive theoretical optimal values of
      hematocrit in vertebrates and collect, from the literature, experimentally
      observed values for 57 animal species. It is an interesting question whether
      optimal hematocrit theory allows one to calculate hematocrit values that are in
      agreement with the observed values in various vertebrate species. For this, we
      first briefly review previous approaches in that theory. Then we check which
      empirical or theoretically derived formulas describing the dependence of
      viscosity on concentration in a suspension lead to the best agreement between the
      theoretical and observed values. We consider both spatially homogeneous and
      heterogeneous distributions of erythrocytes in the blood and also possible
      extensions, like the influence of defective erythrocytes and cases where some
      substances are transported in the plasma. By discussing the results, we
      critically assess the power and limitations of optimal hematocrit theory. One of
      our goals is to provide a systematic overview of different approaches in optimal
      hematocrit theory.

PMID- 22604891
TI  - Airway imaging in disease: gimmick or useful tool?
AB  - Airway remodeling is an important pathophysiological mechanism in a variety of
      chronic airway diseases. Historically investigators have had to use invasive
      techniques such as histological examination of excised tissue to study airway
      wall structure. The last several years has seen a proliferation of relatively
      noninvasive techniques to assess the airway branching pattern, wall thickness,
      and more recently, airway wall tissue components. These methods include computed
      tomography, magnetic resonance imaging, and optical coherence tomography. These
      new imaging technologies have become popular because to understand the physiology
      of lung disease it is important we understand the underlying anatomy. However,
      these new approaches are not standardized or available in all centers so a review
      of their validity and clinical utility is appropriate. This review documents how
      investigators are working hard to correct for inconsistencies between techniques
      so that they become more accepted and utilized in clinical settings. These new
      imaging techniques are very likely to play a frontline role in the study of lung
      disease and will, hopefully, allow clinicians and investigators to better
      understand disease pathogenesis and to design and assess new therapeutic
      interventions.

PMID- 22605000
TI  - Sarcomatoid carcinoma of the bladder after simultaneous kidney-pancreas
      transplant: a case report and review of the literature.
AB  - Carcinosarcoma and sarcomatoid carcinoma of the bladder after organ
      transplantation is higher in comparison to the general population but overall
      occurrence is still very uncommon. Due to the decreased immunitary response
      effects of antirejection drugs, these cancers have aggressive course and respond
      poorly to treatment. Bladder drained pancreatic transplants are associated with a
      number of urologic challenges that can delay the diagnosis and the treatment of
      malignancies of the genito-urinary system. The authors present a case of a rare
      sarcomatoid carcinoma of the bladder following bladder drained simultaneous
      kidney and pancreas transplant and discuss its pathogenesis and clinical
      management.

PMID- 22605001
TI  - Chiari network: a protective filter against pulmonary embolism in a case of
      polycythaemia.
AB  - The Chiari network, a net-like structure within the right atrium, has been
      described as an embryonic remnant of no clinical significance. Its role in
      facilitating paradoxical arterial embolic events and as a potential site for
      thrombus formation however, has been reported in the literature. This case
      illustrates the protective filter-effect of the Chiari network in a 79-year-old
      Caucasian man with an unknown diagnosis of polycythaemia rubra vera who presented
      with clinical signs and symptoms of deep vein thrombosis. Transoesophageal
      echocardiogram confirmed entrapment of a thrombus within the Chiari network,
      which was not visualised following treatment on repeat scanning 1 month later.
      Here the authors describe how the Chiari network may have prevented the
      occurrence of a fatal massive pulmonary embolism in a patient with a high pro
      thrombotic tendency, and review the current literature regarding the action of
      this anatomic variant as risk factor or protector.

PMID- 22605002
TI  - Castleman's disease in a patient with melanoma: the role of VEGF.
AB  - Castleman's disease is a rare lymphoproliferative disorder characterised by lymph
      node follicular hyperplasia with abnormal interfollicular vascular growth. The
      authors report a female patient presenting with erythematous and pruritic skin
      lesion. A shave biopsy of the lesion revealed a Clark level III melanoma and
      sentinel lymph node biopsy revealed a microscopic focus. Staging positron
      emission tomography scan revealed an abnormal soft tissue mass with increased 18F
      fluorodeoxyglucose accumulation in the anterior mediastinum, raising suspicions
      of malignancy. The patient underwent an elective resection of the mass and
      histological sections revealed features of Castleman's disease of the hyaline
      vascular type. Vascular endothelial growth factor (VEGF) has been associated with
      the increased vessel density in this condition. VEGF secretion by tumour cells in
      solid tumours such as melanomas could be a predisposing factor for Castleman's
      disease. Future research is needed to find an association between VEGF-secreting
      solid tumours and the development of lymphoproliferative tumours such as
      Castleman's disease.

PMID- 22605003
TI  - Constrictive pericarditis with a calcified pericardial band at the level of left
      ventricle causing mid-ventricular obstruction.
AB  - An adolescent presented with insidious onset and gradually progressive distension
      of abdomen associated with bilateral ankle swelling of few months duration. He
      had one episode of prolonged low-grade self-limiting febrile illness during
      childhood but had not consulted to doctor and never had been diagnosed as case of
      tuberculosis or acute pericarditis. A detail clinical evaluation showed raised
      central venous pressure, ascites and ankle oedema. Systemic examination was not
      much informative except ejection systolic murmur in third left intercostal space.
      Echocardiography and CT scan heart showed localised thickened pericardium with
      calcific band around the left ventricle at mid ventricle level. The band around
      the heart caused the heart to have a 'dumbbell' appearance with ballooning in
      apical area and a rare mid-ventricular obstruction in the left. A diagnosis of
      chronic constrictive pericarditis with calcific band was made and the patient was
      referred to another centre for cardiac surgery.

PMID- 22605004
TI  - Complete heart block as a complicating feature of a mediastinal lymphoma.
AB  - Malignant lymphomas represent about 9% of cardiac neoplasms. Despite its life
      threatening nature, the cardiac manifestations are often subclinical. In about
      20% of deaths from lymphoma, cardiac involvement is found only in autopsy. The
      authors present the case of a 77-year-old female admitted due to intense back
      pain, vomiting, generalised pruritus, fatigue and weight loss. She had a personal
      history of hypertension and breast cancer was noted 10 years before admission.
      The thoracoabdominopelvic CT showed a mass in the left atrium with extension to
      the right atrium and inferior vena cava, and a paravertebral mass at D10-D11 with
      invasion of the spinal canal and hepatic hilum. The transthoracic paravertebral
      mass biopsy was compatible with a diffuse large B cell lymphoma. The patient
      developed a complete atrioventricular block, with haemodynamic instability,
      requiring urgent chemoreduction of the paracardiac mass and implantation of an
      epicardial pacemaker.

PMID- 22605005
TI  - An adolescent with sickle cell anaemia experiencing disease-related
      complications: priapism and leg ulcer--a management challenge.
AB  - Sickle-cell anaemia (SCA) is a multi-system disease, associated with episodes of
      acute illness and progressive organ damage. Disease severity shows substantial
      variation and it is often a burden for adolescents. Complications such as leg
      ulcer and priapism have a significant impact on quality of life. There are still
      no definitive treatment guidelines available. Considering the embarrassing nature
      of priapism and the dire consequences for erectile dysfunction, it is important
      to inform patients, parents and providers about the relationship of SCA to
      prolonged painful erections. This article will review the pathophysiology and
      treatment options of SCA focusing the complications of leg ulcers, priapism,
      cholelithiasis and retinopathy. The case study of a 14-year-old boy is used to
      present a management challenge of multiple SCA-related complications.

PMID- 22605006
TI  - Right upper quadrant pain and mass in a 41-year-old previously healthy man: a
      presenting feature of HIV-associated extranodal diffuse large B cell lymphoma
      with cardiac involvement.
AB  - With an increasing pandemic of HIV/AIDS, the incidence of HIV-associated lymphoma
      is expected to rise. Here, the authors report a case of a 41-year-old man who
      presented with right upper quadrant pain and mass, and was subsequently diagnosed
      with HIV-associated diffuse large B cell lymphoma (DLBCL) with cardiac
      involvement. This case illustrates some of the uncommon and interesting aspects
      of DLBCL: primary extramedullary extranodal stage IV disease as the presenting
      feature; cardiac involvement at presentation; DLBCL as the only clue to the
      diagnosis of HIV; and management of HIV-associated DLBCL. This case is also a
      reminder of the importance of the routine HIV screening for all patients between
      the ages of 13-64 years, as advocated by centres of disease control and
      prevention.

PMID- 22605007
TI  - Primary hepatic gastrinoma presenting as vague gastrointestinal symptoms.
AB  - A 51-year-old Caucasian female with a 7-year history of intermittent abdominal
      pain and diarrhoea presented to our service. Before presentation, she had been
      successfully treated for Helicobacter pylori infection, but later developed new
      oesophageal ulcerations with exudative lesions that were positive for herpes
      simplex virus, and candida oesophagitis had developed. Biopsies showed chronic
      inactive gastritis with gastric intestinal metaplasia. MRI revealed a solid 3.4*3
      cm lesion in the caudate lobe of the liver, with a 7-mm pancreatic cyst. The
      aspirated pancreatic cyst cytology was benign. On exploratory laporatomy, the
      lesion appeared confined to the caudate lobe, and a resection was performed. The
      pathology was consistent with a well-differentiated neuroendocrine carcinoma with
      vascular invasion and involvement of the liver capsule, although resection
      margins were negative. The patient had complete symptomatic improvement. This
      case re-affirms the high index of suspicion needed to make the diagnosis of
      gastrinoma. If caught in time, surgical removal of primary hepatic gastrinoma can
      be curative.

PMID- 22605008
TI  - Aneurysmal 'pepper-pot' atrial septal defect in an older gentleman with multiple
      cerebrovascular attacks.
AB  - Our patient presented to a large university teaching hospital with a history of
      light-headedness, falls and multiple cerebrovascular ischaemic events. This
      caused a right sided hemiplegia and the patient experienced significant
      functional limitation. Extensive investigations were carried out to exclude any
      causative factors such as carotid artery disease and the patient had all
      identifiable cardiovascular risk factors identified and modified. No significant
      pathology was found and a referral was made to the cardiology service.
      Transthoracic echocardiography revealed a complex type 3 perforate 'pepper pot'
      atrial septal aneurysm with associated thrombus. The patient was commenced on
      warfarin and appropriate rate limiting medication. After discussion of all
      interventional modalities, the patient opted for conservative management.

PMID- 22605019
TI  - A survey of operational characteristics, socioeconomic and health effects of
      scavenging activity in Lagos, Nigeria.
AB  - This study presents the social, economic, health and environmental implications
      of solid waste scavenging activity in Olusosun, one of the government's
      designated open waste dumpsites in Lagos, Nigeria. Using incidental or
      convenience sampling methods of questionnaire administration, 112 scavengers were
      sampled. It was established that scavenging on the site was only possible through
      registration with an associate on site. Recovering items from hills of waste
      involved physical energy and the use of manually-operated rudimentary equipment.
      Thus, 87% of the scavengers were males in their early twenties (minimum age = 19
      years; maximum age = 35 years; mean = 26.7 years; SD = 4.2). The daily mean
      income from the exercise was Naira 480.80 (Naira 160 = $1.00). The most important
      method of arriving at the selling prices of the scavenged products was the use of
      scale measurement. Although the scavengers were aware that scavenging exposed
      them to both environmental and health hazards, they continued scavenging for
      economic and social reasons. The study concluded that because of the level of
      employment provided and the large number of people directly involved (1243 on
      this site alone), outright banning, even when the open dump is closed down,
      without rehabilitating the scavengers will constitute a social, economic and
      security threat to the community. Scavenging should, therefore, be integrated
      fully into the waste-management system and regulated.

PMID- 22605020
TI  - Framework for life cycle sustainability assessment of municipal solid waste
      management systems with an application to a case study in Thailand.
AB  - At present, there are many environmental, economic and social problems associated
      with poor municipal solid waste (MSW) management in Thailand. The development of
      sustainable solid waste management systems is a crucial aspect and should be
      based on an integrated approach. Therefore, an integrated system was designed for
      Nonthaburi Municipality incorporating recycling, anaerobic digestion,
      incineration and landfill technologies. In order to assess sustainability, a
      clear methodology was developed via life cycle thinking and a set of endpoint
      composite indicators has been proposed considering the most critical ultimate
      damages/effects of MSW management on the environment, the economy and society.
      The results showed that the appropriate integration of technologies offers
      important prospects with regards to socio-economic and environmental aspects,
      contributing, therefore, to improved sustainability for the overall MSW
      management system. The methodology and the proposed indicators would be useful in
      strategic planning, including decision- and policy-making with respect to the
      development of appropriate sustainable MSW management systems.

PMID- 22605021
TI  - Optimization of landfill leachate management in the aftercare period.
AB  - The management of sanitary landfills after closure is an important engineering,
      economic and sustainability issue and is referred to as the greatest unresolved
      landfill challenge. Most sanitary landfills are operated according to the dry
      tomb principle, resulting in aftercare periods of hundreds of years. To study
      landfill body behaviour, long-term leachate emissions were studied with anaerobic
      landfill simulators, and a forecast model was developed targeting the behaviour
      of NH(4)-N, COD and chlorides as a function of temperature and the L/S-ratio
      (liquid-to-solid). It was found that NH(4)-N is the decisive factor in leachate
      management, requiring the highest L/S-ratio (around 6) to meet the direct
      discharge limit values. Various scenarios were constructed to find optimal
      leachate management strategies both in large (waste height H = 25 m) and medium
      sized landfills (H = 10 m) with corresponding temperature ranges. The results
      show that by minimizing the aftercare period length with leachate pre-treatment
      and recirculation, both sustainability and economic benefits can be achieved. The
      results provide new views on how to manage the long-term leachate aftercare
      problem. In the case of large landfills, further efforts are needed to reach
      stabilization within a reasonable time frame.

PMID- 22605022
TI  - Application of raster-based GIS techniques in the siting of landfills in Trabzon
      Province, Turkey: a case study.
AB  - One of the most important steps in solid waste management is the selection of an
      appropriate landfill site. The site selection process requires the evaluation and
      analysis of several criteria. However, the traditional evaluation method is not
      sufficient for the site selection process. Geographical information system (GIS)
      technologies are effectively used in the process of site selection, which is a
      spatial problem. This article describes a raster GIS-based landfill site
      selection (LSS) method. This method utilizes a raster-based spatial database in
      which the factors affect the landfill site selection. The final product in this
      method is the cost surface map showing pixel-based values of the appropriate
      areas. Furthermore, this GIS-based LSS method was applied for the evaluation of
      two landfill sites in Trabzon Province in Turkey, for which the traditional
      evaluation method for site selection was used. The suitability values on the cost
      surface map of these two landfills have shown that these sites are not
      appropriate for a solid waste landfill. In conclusion, it was demonstrated that
      the method of raster GIS-based site selection gives more effective results than
      traditional methods.

PMID- 22605023
TI  - Evolution of sorted waste collection: a case study of Spanish cities.
AB  - This work analyses how selective collection evolved over the period 1998-2007 in
      Spanish towns and cities with more than 50 000 inhabitants. To do so, both the
      legislation in force during the years included in the study and logistic factors,
      such as the radius of action of the pick-up points, were taken into account.
      Information about the towns and cities was obtained from a survey sent out in
      1998 and 2007 to the councils of the municipalities included in the study. The
      results obtained in the two years show that the most widely implemented separate
      collection system in 1998 no longer existed in 2007 but, in order to comply with
      the law, had been transformed by adding new fractions, above all that of
      lightweight packaging. To determine whether the targets set by law as regards
      recovery and recycling were met in the two years, an efficiency indicator was
      used to evaluate the effectiveness of the collection systems. Results show how
      separation increased in the paper/board and glass fractions.

PMID- 22605266
TI  - Anchored hybrid enrichment for massively high-throughput phylogenomics.
AB  - The field of phylogenetics is on the cusp of a major revolution, enabled by new
      methods of data collection that leverage both genomic resources and recent
      advances in DNA sequencing. Previous phylogenetic work has required labor
      intensive marker development coupled with single-locus polymerase chain reaction
      and DNA sequencing on clade-by-clade and locus-by-locus basis. Here, we present a
      new, cost-efficient, and rapid approach to obtaining data from hundreds of loci
      for potentially hundreds of individuals for deep and shallow phylogenetic
      studies. Specifically, we designed probes for target enrichment of >500 loci in
      highly conserved anchor regions of vertebrate genomes (flanked by less conserved
      regions) from five model species and tested enrichment efficiency in nonmodel
      species up to 508 million years divergent from the nearest model. We found that
      hybrid enrichment using conserved probes (anchored enrichment) can recover a
      large number of unlinked loci that are useful at a diversity of phylogenetic
      timescales. This new approach has the potential not only to expedite resolution
      of deep-scale portions of the Tree of Life but also to greatly accelerate
      resolution of the large number of shallow clades that remain unresolved. The
      combination of low cost (~1% of the cost of traditional Sanger sequencing and
      ~3.5% of the cost of high-throughput amplicon sequencing for projects on the
      scale of 500 loci * 100 individuals) and rapid data collection (~2 weeks of
      laboratory time) are expected to make this approach tractable even for
      researchers working on systems with limited or nonexistent genomic resources.

PMID- 22605332
TI  - Evidence of the involvement of O-GlcNAc-modified human RNA polymerase II CTD in
      transcription in vitro and in vivo.
AB  - The RNA polymerase II C-terminal domain (CTD), which serves as a scaffold to
      recruit machinery involved in transcription, is modified post-translationally.
      Although the O-GlcNAc modification of RNA polymerase II CTD was documented in
      1993, its functional significance remained obscure. We show that O-GlcNAc
      transferase (OGT) modified CTD serine residues 5 and 7. Drug inhibition of OGT
      and OGA (N-acetylglucosaminidase) blocked transcription during preinitiation
      complex assembly. Polymerase II and OGT co-immunoprecipitated, and OGT is a
      component of the preinitiation complex. OGT shRNA experiments showed that
      reduction of OGT causes a reduction in transcription and RNA polymerase II
      occupancy at several B-cell promoters. These data suggest that the cycling of O
      GlcNAc on and off of polymerase II occurs during assembly of the preinitiation
      complex. Our results define unexpected roles for both the CTD and O-GlcNAc in the
      regulation of transcription initiation in higher eukaryotes.

PMID- 22605333
TI  - The tumor suppressor DiRas3 forms a complex with H-Ras and C-RAF proteins and
      regulates localization, dimerization, and kinase activity of C-RAF.
AB  - The maternally imprinted Ras-related tumor suppressor gene DiRas3 is lost or down
      regulated in more than 60% of ovarian and breast cancers. The anti-tumorigenic
      effect of DiRas3 is achieved through several mechanisms, including inhibition of
      cell proliferation, motility, and invasion, as well as induction of apoptosis and
      autophagy. Re-expression of DiRas3 in cancer cells interferes with the signaling
      through Ras/MAPK and PI3K. Despite intensive research, the mode of interference
      of DiRas3 with the Ras/RAF/MEK/ERK signal transduction is still a matter of
      speculation. In this study, we show that DiRas3 associates with the H-Ras
      oncogene and that activation of H-Ras enforces this interaction. Furthermore,
      while associated with DiRas3, H-Ras is able to bind to its effector protein C
      RAF. The resulting multimeric complex consisting of DiRas3, C-RAF, and active H
      Ras is more stable than the two protein complexes H-Ras.C-RAF or H-Ras.DiRas3,
      respectively. The consequence of this complex formation is a DiRas3-mediated
      recruitment and anchorage of C-RAF to components of the membrane skeleton,
      suppression of C-RAF/B-RAF heterodimerization, and inhibition of C-RAF kinase
      activity.

PMID- 22605334
TI  - DNA transcription and repair: a confluence.
AB  - DNA repair and transcription process complex nucleic acid structures. The
      mammalian cell can cross-utilize select components of either pathway to respond
      to general or special situations arising in either path. These functions comprise
      activity networks capable of addressing unique requirements for each process.
      Here, we discuss examples of such networks that are tailored to respond to the
      demands of both DNA repair and transcription.

PMID- 22605335
TI  - Analysis of nuclear factor-kappaB (NF-kappaB) essential modulator (NEMO) binding
      to linear and lysine-linked ubiquitin chains and its role in the activation of NF
      kappaB.
AB  - Nuclear factor-kappaB (NF-kappaB) essential modulator (NEMO), a component of the
      inhibitor of kappaB kinase (IKK) complex, controls NF-kappaB signaling by binding
      to ubiquitin chains. Structural studies of NEMO provided a rationale for the
      specific binding between the UBAN (ubiquitin binding in ABIN and NEMO) domain of
      NEMO and linear (Met-1-linked) di-ubiquitin chains. Full-length NEMO can also
      interact with Lys-11-, Lys-48-, and Lys-63-linked ubiquitin chains of varying
      length in cells. Here, we show that purified full-length NEMO binds
      preferentially to linear ubiquitin chains in competition with lysine-linked
      ubiquitin chains of defined length, including long Lys-63-linked deca-ubiquitins.
      Linear di-ubiquitins were sufficient to activate both the IKK complex in vitro
      and to trigger maximal NF-kappaB activation in cells. In TNFalpha-stimulated
      cells, NEMO chimeras engineered to bind exclusively to Lys-63-linked ubiquitin
      chains mediated partial NF-kappaB activation compared with cells expressing NEMO
      that binds to linear ubiquitin chains. We propose that NEMO functions as a high
      affinity receptor for linear ubiquitin chains and a low affinity receptor for
      long lysine-linked ubiquitin chains. This phenomenon could explain quantitatively
      distinct NF-kappaB activation patterns in response to numerous cell stimuli.

PMID- 22605336
TI  - The roles of tryptophans in primer synthesis by the DNA primase of bacteriophage
      T7.
AB  - DNA primases catalyze the synthesis of oligoribonucleotides required for the
      initiation of lagging strand DNA synthesis. Prokaryotic primases consist of a
      zinc-binding domain (ZBD) necessary for recognition of a specific template
      sequence and a catalytic RNA polymerase domain. Interactions of both domains with
      the DNA template and ribonucleotides are required for primer synthesis. Five
      tryptophan residues are dispersed in the primase of bacteriophage T7: Trp-42 in
      the ZBD and Trp-69, -97, -147, and -255 in the RNA polymerase domain. Previous
      studies showed that replacement of Trp-42 with alanine in the ZBD decreases
      primer synthesis, whereas substitution of non-aromatic residues for Trp-69
      impairs both primer synthesis and delivery. However, the roles of tryptophan at
      position 97, 147, or 255 remain elusive. To investigate the essential roles of
      these residues, we replaced each tryptophan with the structurally similar
      tyrosine and examined the effect of this subtle alteration on primer synthesis.
      The substitution at position 42, 97, or 147 reduced primer synthesis, whereas
      substitution at position 69 or 255 did not. The functions of the tryptophans were
      further examined at each step of primer synthesis. Alteration of residue 42
      disturbed the conformation of the ZBD and resulted in partial loss of the zinc
      ion, impairing binding to the ssDNA template. Replacement of Trp-97 with tyrosine
      reduced the binding affinity to NTP and the catalysis step. The replacement of
      Trp-147 with tyrosine also impaired the catalytic step. Therefore, Trp-42 is
      important in maintaining the conformation of the ZBD for template binding; Trp-97
      contributes to NTP binding and the catalysis step; and Trp-147 maintains the
      catalysis step.

PMID- 22605337
TI  - Structure of the cytoplasmic region of PelD, a degenerate diguanylate cyclase
      receptor that regulates exopolysaccharide production in Pseudomonas aeruginosa.
AB  - High cellular concentrations of bis-(3',5')-cyclic dimeric guanosine mono
      phosphate (c-di-GMP) regulate a diverse range of phenotypes in bacteria including
      biofilm development. The opportunistic pathogen Pseudomonas aeruginosa produces
      the PEL polysaccharide to form a biofilm at the air-liquid interface of standing
      cultures. Among the proteins required for PEL polysaccharide production, PelD has
      been identified as a membrane-bound c-di-GMP-specific receptor. In this work, we
      present the x-ray crystal structure of a soluble cytoplasmic region of PelD in
      its apo and c-di-GMP complexed forms. The structure of PelD reveals an N-terminal
      GAF domain and a C-terminal degenerate GGDEF domain, the latter of which binds
      dimeric c-di-GMP at an RXXD motif that normally serves as an allosteric
      inhibition site for active diguanylate cyclases. Using isothermal titration
      calorimetry, we demonstrate that PelD binds c-di-GMP with low micromolar affinity
      and that mutation of residues involved in binding not only decreases the affinity
      of this interaction but also abrogates PEL-specific phenotypes in vivo.
      Bioinformatics analysis of the juxtamembrane region of PelD suggests that it
      contains an alpha-helical stalk region that connects the soluble region to the
      transmembrane domains and that similarly to other GAF domain containing proteins,
      this region likely forms a coiled-coil motif that mediates dimerization. PelD
      with Alg44 and BcsA of the alginate and cellulose secretion systems,
      respectively, collectively constitute a group of c-di-GMP receptors that appear
      to regulate exopolysaccharide assembly at the protein level through activation of
      their associated glycosyl transferases.

PMID- 22605338
TI  - Anticancer peptidylarginine deiminase (PAD) inhibitors regulate the autophagy
      flux and the mammalian target of rapamycin complex 1 activity.
AB  - Tumor suppressor genes are frequently silenced in cancer cells by enzymes
      catalyzing epigenetic histone modifications. The peptidylarginine deiminase
      family member PAD4 (also called PADI4) is markedly overexpressed in a majority of
      human cancers, suggesting that PAD4 is a putative target for cancer treatment.
      Here, we have generated novel PAD inhibitors with low micromolar IC(50) in PAD
      activity and cancer cell growth inhibition. The lead compound YW3-56 alters the
      expression of genes controlling the cell cycle and cell death, including SESN2
      that encodes an upstream inhibitor of the mammalian target of rapamycin complex 1
      (mTORC1) signaling pathway. Guided by the gene expression profile analyses with
      YW3-56, we found that PAD4 functions as a corepressor of p53 to regulate SESN2
      expression by histone citrullination in cancer cells. Consistent with the mTORC1
      inhibition by SESN2, the phosphorylation of its substrates including p70S6 kinase
      (p70S6K) and 4E-BP1 was decreased. Furthermore, macroautophagy is perturbed after
      YW3-56 treatment in cancer cells. In a mouse xenograft model, YW3-56 demonstrates
      cancer growth inhibition activity with little if any detectable adverse effect to
      vital organs, whereas a combination of PAD4 and histone deacetylase inhibitors
      further decreases tumor growth. Taken together, our work found that PAD4
      regulates the mTORC1 signaling pathway and that PAD inhibitors are potential
      anticancer reagents that activate tumor suppressor gene expression alone or in
      combination with histone deacetylase inhibitors.

PMID- 22605339
TI  - Limonoid compounds inhibit sphingomyelin biosynthesis by preventing CERT protein
      dependent extraction of ceramides from the endoplasmic reticulum.
AB  - To identify novel inhibitors of sphingomyelin (SM) metabolism, a new and
      selective high throughput microscopy-based screening based on the toxicity of the
      SM-specific toxin, lysenin, was developed. Out of a library of 2011 natural
      compounds, the limonoid, 3-chloro-8beta-hydroxycarapin-3,8-hemiacetal (CHC),
      rendered cells resistant to lysenin by decreasing cell surface SM. CHC treatment
      selectively inhibited the de novo biosynthesis of SM without affecting glycolipid
      and glycerophospholipid biosynthesis. Pretreatment with brefeldin A abolished the
      limonoid-induced inhibition of SM synthesis suggesting that the transport of
      ceramide (Cer) from the endoplasmic reticulum to the Golgi apparatus is affected.
      Unlike the Cer transporter (CERT) inhibitor HPA-12, CHC did not change the
      transport of a fluorescent short chain Cer analog to the Golgi apparatus or the
      formation of fluorescent and short chain SM from the corresponding Cer.
      Nevertheless, CHC inhibited the conversion of de novo synthesized Cer to SM. We
      show that CHC specifically inhibited the CERT-mediated extraction of Cer from the
      endoplasmic reticulum membranes in vitro. Subsequent biochemical screening of 21
      limonoids revealed that some of them, such as 8beta-hydroxycarapin-3,8-hemiacetal
      and gedunin, which exhibits anti-cancer activity, inhibited SM biosynthesis and
      CERT-mediated extraction of Cer from membranes. Model membrane studies suggest
      that 8beta-hydroxycarapin-3,8-hemiacetal reduced the miscibility of Cer with
      membrane lipids and thus induced the formation of Cer-rich membrane domains. Our
      study shows that certain limonoids are novel inhibitors of SM biosynthesis and
      suggests that some biological activities of these limonoids are related to their
      effect on the ceramide metabolism.

PMID- 22605340
TI  - Exploring the structural basis of substrate preferences in Baeyer-Villiger
      monooxygenases: insight from steroid monooxygenase.
AB  - Steroid monooxygenase (STMO) from Rhodococcus rhodochrous catalyzes the Baeyer
      Villiger conversion of progesterone into progesterone acetate using FAD as
      prosthetic group and NADPH as reducing cofactor. The enzyme shares high sequence
      similarity with well characterized Baeyer-Villiger monooxygenases, including
      phenylacetone monooxygenase and cyclohexanone monooxygenase. The comparative
      biochemical and structural analysis of STMO can be particularly insightful with
      regard to the understanding of the substrate-specificity properties of Baeyer
      Villiger monooxygenases that are emerging as promising tools in biocatalytic
      applications and as targets for prodrug activation. The crystal structures of
      STMO in the native, NADP(+)-bound, and two mutant forms reveal structural details
      on this microbial steroid-degrading enzyme. The binding of the nicotinamide ring
      of NADP(+) is shifted with respect to the flavin compared with that observed in
      other monooxygenases of the same class. This finding fully supports the idea that
      NADP(H) adopts various positions during the catalytic cycle to perform its
      multiple functions in catalysis. The active site closely resembles that of
      phenylacetone monooxygenase. This observation led us to discover that STMO is
      capable of acting also on phenylacetone, which implies an impressive level of
      substrate promiscuity. The investigation of six mutants that target residues on
      the surface of the substrate-binding site reveals that enzymatic conversions of
      both progesterone and phenylacetone are largely insensitive to relatively drastic
      amino acid changes, with some mutants even displaying enhanced activity on
      progesterone. These features possibly reflect the fact that these enzymes are
      continuously evolving to acquire new activities, depending on the emerging
      availabilities of new compounds in the living environment.

PMID- 22605341
TI  - Novel one-step mechanism for tRNA 3'-end maturation by the exoribonuclease RNase
      R of Mycoplasma genitalium.
AB  - Mycoplasma genitalium is expected to metabolize RNA using unique pathways because
      its minimal genome encodes very few ribonucleases. In this work, we report that
      the only exoribonuclease identified in M. genitalium, RNase R, is able to remove
      tRNA 3'-trailers and generate mature 3'-ends. Several sequence and structural
      features of a tRNA precursor determine its precise processing at the 3'-end by
      RNase R in a purified system. The aminoacyl-acceptor stem plays a major role in
      stopping RNase R digestion at the mature 3'-end. Disruption of the stem causes
      partial or complete degradation of the pre-tRNA by RNase R, whereas extension of
      the stem results in the formation of a product terminating downstream at the new
      mature 3'-end. In addition, the 3'-terminal CCA sequence and the discriminator
      residue influence the ability of RNase R to stop at the mature 3'-end. RNase R
      mediated generation of the mature 3'-end prefers a sequence of RCCN at the 3'
      terminus of tRNA. Variations of this sequence may cause RNase R to trim further
      and remove terminal CA residues from the mature 3'-end. Therefore, M. genitalium
      RNase R can precisely remove the 3'-trailer of a tRNA precursor by recognizing
      features in the terminal domains of tRNA, a process requiring multiple RNases in
      most bacteria.

PMID- 22605342
TI  - Distinct functions of regions 1.1 and 1.2 of RNA polymerase sigma subunits from
      Escherichia coli and Thermus aquaticus in transcription initiation.
AB  - RNA polymerase (RNAP) from thermophilic Thermus aquaticus is characterized by
      higher temperature of promoter opening, lower promoter complex stability, and
      higher promoter escape efficiency than RNAP from mesophilic Escherichia coli. We
      demonstrate that these differences are in part explained by differences in the
      structures of the N-terminal regions 1.1 and 1.2 of the E. coli sigma(70) and T.
      aquaticus sigma(A) subunits. In particular, region 1.1 and, to a lesser extent,
      region 1.2 of the E. coli sigma(70) subunit determine higher promoter complex
      stability of E. coli RNAP. On the other hand, nonconserved amino acid
      substitutions in region 1.2, but not region 1.1, contribute to the differences in
      promoter opening between E. coli and T. aquaticus RNAPs, likely through affecting
      the sigma subunit contacts with DNA nucleotides downstream of the -10 element. At
      the same time, substitutions in sigma regions 1.1 and 1.2 do not affect promoter
      escape by E. coli and T. aquaticus RNAPs. Thus, evolutionary substitutions in
      various regions of the sigma subunit modulate different steps of the open
      promoter complex formation pathway, with regions 1.1 and 1.2 affecting promoter
      complex stability and region 1.2 involved in DNA melting during initiation.

PMID- 22605343
TI  - The Kruppel-associated box repressor domain can induce reversible
      heterochromatization of a mouse locus in vivo.
AB  - The study of chromatin and its regulators is key to understanding and
      manipulating transcription. We previously exploited the Kruppel-associated box
      (KRAB) transcriptional repressor domain, present in hundreds of vertebrate
      specific zinc finger proteins, to assess the effect of its binding to gene
      bodies. These experiments revealed that the ectopic and doxycycline (dox)
      controlled tet repressor KRAB fusion protein (tTRKRAB) can induce reversible and
      long-range silencing of cellular promoters. Here, we extend this system to in
      vivo applications and use tTRKRAB to achieve externally controllable repression
      of an endogenous mouse locus. We employed lentiviral-mediated transgenesis with
      promoterless TetO-containing gene traps to engineer a mouse line where the
      endogenous kinesin family member 2A (Kif2A) promoter drives a YFP reporter gene.
      When these mice were crossed to animals expressing the TetO-binding tTRKRAB
      repressor, this regulator was recruited to the Kif2A locus, and YFP expression
      was reduced. This effect was reversed when dox was given to embryos or adult
      mice, demonstrating that the cellular Kif2A promoter was only silenced upon
      repressor binding. Molecular analyses confirmed that tTRKRAB induced
      transcriptional repression through the spread of H3K9me3-containing
      heterochromatin, without DNA methylation of the trapped Kif2A promoter.
      Therefore, we demonstrate that targeting of tTRKRAB to a gene body in vivo
      results in reversible transcriptional repression through the spreading of
      facultative heterochromatin. This finding not only sheds light on KRAB-mediated
      transcriptional processes, but also suggests approaches for the externally
      controllable and reversible modulation of chromatin and transcription in vivo.

PMID- 22605345
TI  - Palliative care in advanced cancer patients: waiting for Godot.

PMID- 22605346
TI  - Palliative care in advanced cancer patients: how and when? And where?

PMID- 22605360
TI  - Perfectionistic profiles among elite athletes and differences in their
      motivational orientations.
AB  - Although there is an emerging body of research that has examined perfectionistic
      clusters in the general population, few studies have explored such profiles in
      athlete samples. The purposes of this research were to explore perfectionistic
      profiles within a sample of elite athletes and the differences between them on
      key motivational variables. A sample of 423 elite athletes (179 males, 244
      females) aged between 14 and 66 years (M = 25.64; SD = 8.57) from a variety of
      team (e.g., rowing, hockey, baseball, rugby) and individual sports (e.g.,
      cycling, athletics, triathlon, gymnastics) completed a multisection questionnaire
      including measures of sport perfectionism, motivation regulation, achievement
      goals, and fear of failure. Cluster analyses revealed the existence of three
      perfectionism profiles, namely, nonperfectionists, maladaptive perfectionists,
      and adaptive perfectionists. Subsequent analyses generally supported the
      robustness of these perfectionism profiles in terms of differential motivational
      orientations (achievement goals, fear of failure, and motivation regulation) in
      hypothesized directions. Overall, the differences in motivational orientations
      between the three clusters supported a categorical conceptualization of
      perfectionism.

PMID- 22605361
TI  - Assessing coach motivation: the development of the Coach Motivation Questionnaire
      (CMQ).
AB  - The aim of this research was to develop and assess the psychometric properties of
      the Coach Motivation Questionnaire (CMQ). Study 1 focused on the compilation and
      pilot testing of potential questionnaire items. Consistent with self
      determination theory, items were devised to tap into six forms of motivation:
      amotivation, external regulation, introjected regulation, identified regulation,
      integrated regulation, and intrinsic motivation. The purpose of the second study
      (N = 556) was to empirically examine the psychometric properties of the CMQ.
      Items were subjected to confirmatory factor analyses to determine the fit of the
      a priori model. In addition, the validity of the questionnaire was assessed
      through links with the theoretically related concepts of intrinsic need
      satisfaction, well-being, and goal orientation. Together with test-retest
      reliability (Study 3), these results showed preliminary support for the
      psychometric properties of the CMQ. Finally, using an independent sample (N =
      254), the fourth study confirmed the factor structure and supports the use of the
      CMQ in future coaching research.

PMID- 22605362
TI  - Put yourself in their boots: effects of empathy on emotion and aggression.
AB  - Aggression has been linked to empathy and emotions (e.g., guilt) in cross
      sectional studies. The purpose of this experiment was to examine the effects of
      empathy on emotional reactions to aggression and the role of guilt in the empathy
      aggression relationship. Seventy-one undergraduate sport and exercise science
      students with a mean age of 19.56 (SD = 1.94) years were randomly assigned to
      either a high- or a low-empathy group. We experimentally manipulated empathy
      using perspective taking instructions and examined the following: (a)
      participants' emotional reactions to images of aggressive acts; (b) their
      reported likelihood to aggress in a hypothetical sport situation; and (c) the
      extent to which they anticipated feeling guilt if they were to engage in an
      aggressive act. Participants in the high-empathy group experienced stronger
      negative emotional reactions to images of aggressive acts and reported lower
      likelihood to aggress than did those in the low-empathy group. Anticipated guilt
      partially mediated the effects of empathy on reported likelihood to aggress. Our
      findings suggest that empathy may help reduce aggressive behavior and highlight
      the potential mediating role of guilt.

PMID- 22605363
TI  - Pregnancy--should women put up their feet or lace up their running shoes?: Self
      presentation and the exercise stereotype phenomenon during pregnancy.
AB  - Little is known about how women who exercise during pregnancy are perceived. The
      purpose of this study was to investigate whether the positive exercise stereotype
      (i.e., the general tendency for exercisers to be evaluated more positively than
      nonexercisers) extends to pregnancy. Adult women (N = 202, mean age = 38.55
      years, SD = 13.46) were randomly assigned to read a description of one of the
      following pregnant female targets: regular exerciser, active living, excessive
      exerciser, nonexerciser, or control. Participants then rated the target on 12
      personality and 8 physical dimensions. MANOVAs revealed a significant main effect
      for both physical and personality attributes (p < .05). The regular exerciser and
      active living target received the most positive ratings on both physical and
      personality dimensions. Whereas the excessive exerciser received high ratings on
      most physical characteristics, this target was also perceived as meaner and
      sadder, and having fewer friends than all other targets.

PMID- 22605364
TI  - Three generalizability studies of the components of perceived coach support.
AB  - Coaches are important providers of social support, but what influences us to
      perceive our coaches as supportive or unsupportive? We investigated the extent to
      which perceptions of coach support reflect characteristics of athletes and
      coaches, as well as relational components. In three studies, athletes judged the
      actual or hypothetical supportiveness of various coaches. The methods of
      generalizability theory permitted us to conclude that perceptions of coach
      support primarily reflected relational components, with characteristics both of
      athletes and coaches also independently playing (lesser) roles. These findings
      suggest that athletes may systematically disagree on the supportiveness of their
      coaches.

PMID- 22605365
TI  - Virtual and live social facilitation while exergaming: competitiveness moderates
      exercise intensity.
AB  - Grounded in social facilitation theory, this study compared the impact on
      exercise intensity of a virtual versus a live competitor, when riding a virtual
      reality-enhanced stationary bike ("cybercycle"). It was hypothesized that
      competitiveness would moderate effects. Twenty-three female college students were
      exposed to three conditions on a cybercycle: solo training, virtual competitor,
      and live competitor. After training without a competitor (solo condition for
      familiarization with equipment), participants competed against a virtual avatar
      or live rider (random order of presentation). A repeated-measures analysis
      revealed a significant condition (virtual/live) by competitiveness (high/low)
      interaction for exercise intensity (watts). More competitive participants
      exhibited significantly greater exercise intensity when competing against a live
      versus virtual competitor. The implication is that live competitors can have an
      added social facilitation effect and influence exercise intensity, although
      competitiveness moderates this effect.

PMID- 22605366
TI  - Autonomous regulation mode moderates the effect of actual physical activity on
      affective states: an ambulant assessment approach to the role of self
      determination.
AB  - Studies have shown that physical activity influences affective states. However,
      studies have seldom depicted these associations in ongoing real-life situations,
      and there is no investigation showing that motivational states (i.e., more or
      less autonomously regulated) would moderate these effects in situ. To investigate
      the interaction of autonomous regulation and actual physical activity (aPA) with
      affective states, we use an ambulatory assessment approach. The participants were
      44 university students (mean age: 26.2 +/- 3.2 years). We assessed aPA through 24
      hr accelerometry and affective states and autonomous regulation via electronic
      diaries. Palmtop devices prompted subjects every 45 min during a 14-hr daytime
      period. We performed hierarchical multilevel analyses. Both aPA and autonomous
      regulation significantly influenced affective states. The interaction was
      significant for two affects. The higher the volume of aPA and thereby the more
      autonomously regulated the preceding bout of aPA was, the more our participants
      felt energized (r = .16) but agitated (r = -.18).

PMID- 22605381
TI  - Structural basis for the acyltransferase activity of lecithin:retinol
      acyltransferase-like proteins.
AB  - Lecithin:retinol acyltransferase-like proteins, also referred to as HRAS-like
      tumor suppressors, comprise a vertebrate subfamily of papain-like or NlpC/P60
      thiol proteases that function as phospholipid-metabolizing enzymes. HRAS-like
      tumor suppressor 3, a representative member of this group, plays a key role in
      regulating triglyceride accumulation and energy expenditure in adipocytes and
      therefore constitutes a novel pharmacological target for treatment of metabolic
      disorders causing obesity. Here, we delineate a catalytic mechanism common to
      lecithin:retinol acyltransferase-like proteins and provide evidence for their
      alternative robust lipid-dependent acyltransferase enzymatic activity. We also
      determined high resolution crystal structures of HRAS-like tumor suppressor 2 and
      3 to gain insight into their active site architecture. Based on this structural
      analysis, two conformational states of the catalytic Cys-113 were identified that
      differ in reactivity and thus could define the catalytic properties of these two
      proteins. Finally, these structures provide a model for the topology of these
      enzymes and allow identification of the protein-lipid bilayer interface. This
      study contributes to the enzymatic and structural understanding of HRAS-like
      tumor suppressor enzymes.

PMID- 22605389
TI  - Can procalcitonin distinguish infectious fever from tumor-related fever in non
      neutropenic cancer patients?
AB  - BACKGROUND: Procalcitonin (PCT) has been proposed as a marker of infection and
      was studied in neutropenic patients. This study investigated its role in non
      neutropenic febrile cancer patients (NNCPs). METHODS: Between July 2009 and July
      2010, a total of 248 NNCPs with fever were studied. PCT was measured in plasma
      within 24 hours of fever onset and 4 to 7 days thereafter, using a Kryptor system
      with a lower limit of quantitation of 0.075 ng/mL. Patients' clinical,
      microbiological, and radiological data were reviewed to make the diagnosis and
      were correlated with PCT levels. RESULTS: This study included 30 patients with
      bloodstream infection (BSI), 60 with localized bacterial infection, 141 with no
      documented infection, and 8 with tumor-related fever. Most patients (98%) were
      inpatients or admitted to the hospital during the study. Patients with BSI had
      significantly higher PCT levels than did those with documented localized
      infections (P = .048) and no documented infection (P = .011). PCT levels were
      significantly higher in septic patients than in those without sepsis (P = .012).
      Patients with stage IV disease or metastasis had significantly higher baseline
      PCT levels than did those with early stages of cancer (P < .05). PCT levels
      dropped significantly in patients with bacterial infections in response to
      antibiotics (P < .0001). CONCLUSIONS: Baseline PCT levels are predictive of BSI
      and sepsis in NNCPs. They may be predictors of metastasis and advanced cancer.
      Subsequent decrease in PCT levels in response to antibiotics is suggestive of
      bacterial infection. Larger trials are needed to confirm the results of this
      pilot study.

PMID- 22605405
TI  - Use of serum procalcitonin to detect bacterial infection in patients with
      autoimmune diseases: a systematic review and meta-analysis.
AB  - OBJECTIVE: To systematically review evidence of the accuracy of the procalcitonin
      test for diagnosis of bacterial infection in patients with autoimmune disease.
      METHODS: The major databases Medline, EMBase, and the Cochrane Library were
      searched for studies published between January 1966 and October 2011 that
      evaluated procalcitonin, alone or in comparison with other laboratory markers
      such as C-reactive protein (CRP), as a diagnostic marker for bacterial infection
      in patients with autoimmune disease and provided sufficient data to permit
      construction of 2 * 2 tables. RESULTS: Nine studies were included in the final
      meta-analysis. The area under the summary receiver operating characteristic curve
      values were 0.91 (95% confidence interval [95% CI] 0.88-0.93) for procalcitonin
      and 0.81 (95% CI 0.78-0.84) for CRP. In general, testing for procalcitonin was
      highly specific for identifying infectious complications, although it was not as
      sensitive as testing for CRP. Pooled sensitivity was 0.75 (95% CI 0.63-0.84) for
      procalcitonin tests and 0.77 (95% CI 0.67-0.85) for CRP tests. Pooled specificity
      was 0.90 (95% CI 0.85-0.93) for procalcitonin tests and 0.56 (95% CI 0.25-0.83)
      for CRP tests. The positive likelihood ratio for procalcitonin (7.28 [95% CI 5.10
      10.38]) was sufficiently high to qualify procalcitonin testing as a rule-in
      diagnostic tool, while the negative likelihood ratio (0.28 [95% CI 0.18-0.40])
      was not sufficiently low to qualify procalcitonin testing as a reliable rule-out
      diagnostic tool. CONCLUSION: Procalcitonin has higher diagnostic value than CRP
      for the detection of bacterial sepsis in patients with autoimmune disease, and
      the test for procalcitonin is more specific than sensitive. A procalcitonin test
      is not recommended to be used in isolation as a rule-out tool.

PMID- 22605406
TI  - Screening performance for trisomy 21 comparing first trimester combined screening
      and a first trimester contingent screening protocol including ductus venosus and
      tricuspid flow.
AB  - OBJECTIVE: To compare the standard first trimester combined risk assessment for
      trisomy 21 with a contingent screening protocol including tricuspid flow and
      ductus venosus flow. MATERIAL AND METHOD: Women with singleton pregnancies and a
      first trimester combined risk assessment>1:1000 were included. They all had
      additional assessment of the ductus venosus and the tricuspid flow. We compared
      screening performance in two screening strategies: (a) First trimester combined
      screening strategy based on the individual risk results from the routine
      screening test and (b) Contingent screening strategy based on a combination of
      the routine test results and additional ultrasound markers. RESULTS: We included
      917 women in the study, 894 in the euploid group and 23 in the trisomy 21 group.
      Using a contingent screening strategy resulted in a significant decrease in
      screen positive rate from 48.3% to 17.7% (p<0.001) in the studied population.
      There was no statistical difference in detection rate between the two screening
      strategies. CONCLUSION: There is increasing evidence in favour of using
      additional ultrasound markers as part of contingent screening protocols in the
      first trimester. We do suggest performing further studies in routine clinical
      settings to provide validation of the available risk algorithms.

PMID- 22605411
TI  - A crown ether appended super gelator with multiple stimulus responsiveness.
AB  - A crown ether appended super gelator is designed and synthesized. It can gel a
      variety of organic solvents and shows excellent gelation properties with both low
      critical gelation concentration and short gelation time. Due to the introduction
      of the crown ether moiety and a secondary ammonium unit, the supramolecular gels
      show reversible gel-sol transitions. The supramolecular gels can also be molded
      into shape-persistent and free-standing objects.

PMID- 22605430
TI  - Economic survivorship stress is associated with poor health-related quality of
      life among distressed survivors of hematopoietic stem cell transplantation.
AB  - BACKGROUND: Hematopoietic stem cell transplantation is a demanding cancer
      treatment associated with enduring physical and psychological complications.
      Survivors' well-being may be further compromised by exposure to chronic stressors
      common to this population, including difficulties arising from costly medical
      care, changes in employment status, and health insurance coverage. Thus, we
      hypothesized that financial, employment, and insurance stressors (collectively
      referred to as economic survivorship stressors) would be associated with poorer
      health-related quality of life (HRQOL) among hematopoietic stem cell
      transplantation survivors. METHODS: Survivors (n = 181; M = 640 days post
      transplant) completed the measures of study variables through mailed
      questionnaires and telephone interviews. Hierarchical regression analyses were
      conducted to test the hypothesized associations between economic survivorship
      stressors and HRQOL, and to examine whether social and situational factors
      interact with survivors' stress perceptions to predict HRQOL. RESULTS: Greater
      financial and employment stress were associated with poorer functioning across
      multiple HRQOL domains, even after controlling for the effects of possible
      confounding sociodemographic and medical variables. Insurance stress was not
      associated with HRQOL. Some associations were moderated by situational factors
      including timing of the current financial crisis and portion of the transplant
      paid for by health insurance. CONCLUSIONS: Hematopoietic stem cell
      transplantation survivors can face serious economic challenges during recovery.
      Results suggest the value of viewing these challenges as chronic stressors
      capable of reducing survivors' mental and physical well-being. Identifying
      resources and skills that help survivors cope with these demands is an important
      goal for clinicians and researchers.

PMID- 22605431
TI  - 45,X/46,XY mosaicism: phenotypic characteristics, growth, and reproductive
      function--a retrospective longitudinal study.
AB  - CONTEXT: Most previous studies of 45,X/46,XY mosaicism are case reports or have
      described single aspects of the disease. OBJECTIVE: The objective was to provide
      longitudinal data of patients with 45,X/46,XY mosaicism. DESIGN: This was a
      retrospective, longitudinal study conducted from June 1990 to January 2012.
      SETTING: The study took place at a tertiary pediatric and andrological referral
      center. PATIENTS OR OTHER PARTICIPANTS: Twenty-five patients (18 boys, seven
      girls) with 45,X/46,XY mosaicism and its variants were included and were compared
      to healthy controls. INTERVENTION(S): No interventions were included in the
      study. MAIN OUTCOME MEASURE(S): Phenotypes were scored using external
      masculinization scores. Serum LH, FSH, testosterone, estradiol, and inhibin B
      levels were reported in male patients. IGF-I levels and height were reported in
      all patients. Available biopsies/gonadectomies were histologically examined.
      RESULTS: Fourteen of 18 males had external masculinization scores consistent with
      normal virilization. Ten of 11 male patients experienced spontaneous puberty.
      Median height sd score was -2.0 (range, -3 to 0.3) for males and -2.2 (range, 
      2.5 to -1.4) for females, both considerably below genetic potential. Median 1-yr
      height gain after GH treatment in seven patients was 0.5 sd (0.1 to 1.2). All
      tissue samples from 15 patients (eight males, seven females) revealed abnormal
      gonadal histology. Four patients had carcinoma in situ (CIS); two had tissue
      samples available from early childhood, one showing CIS. CONCLUSIONS: Gonadal
      function in most 45,X/46,XY males, even those with genital ambiguity, seems
      sufficient for spontaneous puberty. Short stature and 45,X/46,XY mosaicism seem
      associated, but patients appear to benefit from GH treatment. Histology from two
      patients with biopsies from early childhood indicates that CIS originates before
      puberty.

PMID- 22605443
TI  - The association between acculturation and recreational computer use among Latino
      adolescents in California.
AB  - BACKGROUND: Physical inactivity like recreational computer use is a likely factor
      in the rising obesity prevalence among Latino adolescents. OBJECTIVES: Using the
      data from California Health Interview Survey, we test the hypothesis whether
      acculturation is associated with recreational computer use among Latino
      adolescents. METHODS: We run linear regressions of the weekly time spent on
      recreational computer use among Latino adolescents, stratified first by gender
      and then by age group (12-14 and 15-17 years). Years living in the United States
      and language at home are used as key variables for acculturation. RESULTS: For
      all four sub-populations, living in the United States for less than 5 years is
      significantly associated with fewer hours on recreational computer use, compared
      with those US-born. Among female adolescents, those who lived in the United
      States for 10 years or more spent fewer hours on recreational computer use than
      those US-born. Among adolescents under 15, speaking English only and speaking
      English plus another language are both significantly associated with more hours
      on recreational computer use, compared with those who speak a non-English
      language at home. CONCLUSION: Educators and health professionals should heed the
      Latino adolescents' possible increase in recreational computer use.

PMID- 22605456
TI  - A sequential treatment algorithm for infants with stage 4s neuroblastoma and
      massive hepatomegaly.
AB  - Infants with 4s neuroblastoma (NB) and massive hepatomegaly have a guarded
      prognosis and mortality approaches 30%. We report on eight patients with 4s NB
      and massive hepatomegaly treated with multiple modalities. One patient had
      spontaneous tumor regression. Three patients had progressive disease and
      responded to chemotherapy. Four patients progressed despite intravenous
      chemotherapy, of whom two died, and two were salvaged with hepatic intra-arterial
      chemoembolization. Treatment of infants with stage 4s NB with massive
      hepatomegaly should be individualized based on disease course. A sequential
      approach with observation, intravenous chemotherapy, and intra-arterial
      chemoembolization, may improve the outcome of these infants.

PMID- 22605432
TI  - Vitamin D with calcium reduces mortality: patient level pooled analysis of 70,528
      patients from eight major vitamin D trials.
AB  - INTRODUCTION: Vitamin D may affect multiple health outcomes. If so, an effect on
      mortality is to be expected. Using pooled data from randomized controlled trials,
      we performed individual patient data (IPD) and trial level meta-analyses to
      assess mortality among participants randomized to either vitamin D alone or
      vitamin D with calcium. SUBJECTS AND METHODS: Through a systematic literature
      search, we identified 24 randomized controlled trials reporting data on mortality
      in which vitamin D was given either alone or with calcium. From a total of 13
      trials with more than 1000 participants each, eight trials were included in our
      IPD analysis. Using a stratified Cox regression model, we calculated risk of
      death during 3 yr of treatment in an intention-to-treat analysis. Also, we
      performed a trial level meta-analysis including data from all studies. RESULTS:
      The IPD analysis yielded data on 70,528 randomized participants (86.8% females)
      with a median age of 70 (interquartile range, 62-77) yr. Vitamin D with or
      without calcium reduced mortality by 7% [hazard ratio, 0.93; 95% confidence
      interval (CI), 0.88-0.99]. However, vitamin D alone did not affect mortality, but
      risk of death was reduced if vitamin D was given with calcium (hazard ratio,
      0.91; 95% CI, 0.84-0.98). The number needed to treat with vitamin D plus calcium
      for 3 yr to prevent one death was 151. Trial level meta-analysis (24 trials with
      88,097 participants) showed similar results, i.e. mortality was reduced with
      vitamin D plus calcium (odds ratio, 0.94; 95% CI, 0.88-0.99), but not with
      vitamin D alone (odds ratio, 0.98; 95% CI, 0.91-1.06). CONCLUSION: Vitamin D with
      calcium reduces mortality in the elderly, whereas available data do not support
      an effect of vitamin D alone.

PMID- 22605457
TI  - Hemophagocytic syndrome in a 4-month-old infant with biotinidase deficiency.
AB  - Hemophagocytic syndromes such as hemophagocytic lymphohistiocytosis (HLH) are
      life-threatening hyperinflammatory conditions caused by inherited or acquired
      immune disorders. Awareness of the clinical symptoms and diagnostic criteria for
      hemophagocytic syndromes is crucial to start timely life-saving therapy. We
      present a case of a 4-month-old boy presenting with HLH. However, the patient was
      subsequently diagnosed with biotinidase deficiency and was successfully treated
      with biotin-replacement therapy, upon which the hemophagocytic syndrome ceased.
      Subsequent laboratory evaluations revealed normal lymphocyte cytotoxicity and no
      mutations in genes associated with familial HLH were found. Biotinidase
      deficiency should be considered as a differential diagnosis of patients
      fulfilling HLH criteria.

PMID- 22605458
TI  - Mevalonate metabolism regulates Basal breast cancer stem cells and is a potential
      therapeutic target.
AB  - There is increasing evidence that breast tumors are organized in a hierarchy,
      with a subpopulation of tumorigenic cancer cells, the cancer stem cells (CSCs),
      which sustain tumor growth. The characterization of protein networks that govern
      CSC behavior is paramount to design new therapeutic strategies targeting this
      subpopulation of cells. We have sought to identify specific molecular pathways of
      CSCs isolated from 13 different breast cancer cell lines of luminal or
      basal/mesenchymal subtypes. We compared the gene expression profiling of cancer
      cells grown in adherent conditions to those of matched tumorsphere cultures. No
      specific pathway was identified to be commonly regulated in luminal tumorspheres,
      resulting from a minor CSC enrichment in tumorsphere passages from luminal cell
      lines. However, in basal/mesenchymal tumorspheres, the enzymes of the mevalonate
      metabolic pathway were overexpressed compared to those in cognate adherent cells.
      Inhibition of this pathway with hydroxy-3-methylglutaryl CoA reductase blockers
      resulted in a reduction of breast CSC independent of inhibition of cholesterol
      biosynthesis and of protein farnesylation. Further modulation of this metabolic
      pathway demonstrated that protein geranylgeranylation (GG) is critical to breast
      CSC maintenance. A small molecule inhibitor of the geranylgeranyl transferase I
      (GGTI) enzyme reduced the breast CSC subpopulation both in vitro and in primary
      breast cancer xenografts. We found that the GGTI effect on the CSC subpopulation
      is mediated by inactivation of Ras homolog family member A (RHOA) and increased
      accumulation of P27(kip1) in the nucleus. The identification of protein GG as a
      major contributor to CSC maintenance opens promising perspectives for CSC
      targeted therapy in basal breast cancer.

PMID- 22605461
TI  - Air-stable and high-mobility n-channel organic transistors based on small
      molecule/polymer semiconducting blends.
AB  - Use of a carefully designed small-molecule organic semiconductor based on an
      oxidized diketopyrrolopyrrole core enables the fabrication by solution processing
      of electron-transporting (n-channel) blend-based organic thin-film transistors
      with high electron mobility (0.5 cm(2)/Vs) and high operating stability even when
      the devices are exposed to ambient air for prolonged periods of time.

PMID- 22605463
TI  - Antigen-specific transforming growth factor beta-induced Treg cells, but not
      natural Treg cells, ameliorate autoimmune arthritis in mice by shifting the
      Th17/Treg cell balance from Th17 predominance to Treg cell predominance.
AB  - OBJECTIVE: Transferred CD4+CD25+FoxP3+ Treg cells can prevent autoimmune disease,
      but generally fail to ameliorate established disease. This study was undertaken
      to compare the effects of antigen-specific Treg cells induced with interleukin-2
      (IL-2) and transforming growth factor beta (TGFbeta) ex vivo (induced Treg
      [iTreg] cells) to the effects of equivalent expanded thymus-derived natural Treg
      (nTreg) cells on established collagen-induced arthritis (CIA). METHODS: CIA was
      induced in DBA/1 mice by immunization with type II collagen (CII), and before or
      shortly after immunization, mice were treated with iTreg or nTreg cells that were
      generated or expanded in vitro. Clinical scores were determined. Inflammatory
      responses were determined by measuring the levels of anti-CII antibody in the
      serum and examining the histologic features of the mouse joints. The Th1/Th17
      mediated autoreactive response was evaluated by determining the cytokine profile
      of the draining lymph node (LN) cells of the mice by flow cytometry. RESULTS:
      Following transfer, nTreg cells exhibited decreased FoxP3 and Bcl-2 expression
      and decreased suppressive activity, and many converted to Th17 cells. In
      contrast, transferred iTreg cells were more numerous, retained FoxP3 expression
      and their suppressive activity in the presence of IL-6, and were resistant to
      Th17 conversion. Notably, 10 days after the transfer of donor iTreg cells,
      predominance was shifted from Th17 cells to Treg cells in the draining LNs of
      recipient mice. CONCLUSION: These findings provide evidence that transferred
      TGFbeta-induced iTreg cells are more stable and functional than nTreg cells in
      mice with established autoimmunity. Moreover, iTreg cells can have tolerogenic
      effects even in the presence of ongoing inflammation. The therapeutic potential
      of human iTreg cells in subjects with chronic, immune-mediated inflammatory
      diseases should be investigated.

PMID- 22605470
TI  - Templation, water content, and zeta potential of polyelectrolyte nanoassemblies:
      a comparison between polyelectrolyte multilayers and brushes.
AB  - This feature article deals with the self assembly and physical chemistry of
      polyelectrolytes: multilayers and brushes. The article highlights the interesting
      behavior of polyelectrolytes in nanoscale assemblies, giving more insight into
      the complexity of the formation of the assemblies. The water content of
      multilayers and brushes is studied during the assembly and in different ionic
      strengths. Similarities are found in the behavior of the brushes and multilayers
      with ionic strength, with regard to changes in the thickness and the water
      content. An invariance of the zeta potential with ionic strength is also observed
      for both systems, which can be explained as a result of conformational changes of
      the polymer chains. Finally, the combination of brushes and multilayers for
      surface modification is presented.

PMID- 22605471
TI  - Effects of triclosan on marine benthic and epibenthic organisms.
AB  - Triclosan is an antimicrobial compound that has been widely used in consumer
      products such as toothpaste, deodorant, and shampoo. Because of its widespread
      use, triclosan has been detected in various environmental media, including
      wastewater, sewage sludge, surface waters, and sediments. Triclosan is acutely
      toxic to numerous aquatic organisms, but very few studies have been performed on
      estuarine and marine benthic organisms. For whole sediment toxicity tests, the
      sediment-dwelling estuarine amphipod, Ampelisca abdita, and the epibenthic mysid
      shrimp, Americamysis bahia, are commonly used organisms. In the present study,
      median lethal concentration values (LC50) were obtained for both of these
      organisms using water-only and whole sediment exposures. Acute 96-h water-only
      toxicity tests resulted in LC50 values of 73.4 and 74.3 ug/L for the amphipod and
      mysid, respectively. For the 7-d whole sediment toxicity test, LC50 values were
      303 and 257 mg/kg (dry wt) for the amphipod and mysid, respectively. Using
      equilibrium partitioning theory, these whole sediment values are equivalent to
      interstitial water LC50 values of 230 and 190 ug/L for the amphipod and mysid,
      respectively, which are within a threefold difference of the observed 96-h LC50
      water-only values. Triclosan was found to accumulate in polychaete tissue in a 28
      d bioaccumulation study with a biota-sediment accumulation factor of 0.23 kg
      organic carbon/kg lipid. These data provide some of the first toxicity data for
      triclosan with marine benthic and epibenthic species while also indicating a need
      to better understand the effects of other forms of sediment carbon, triclosan
      ionization, and organism metabolism of triclosan on the chemical's behavior and
      toxicity in the aquatic environment.

PMID- 22605478
TI  - Gain of chromosome 8q is associated with metastases and poor survival of patients
      with clear cell renal cell carcinoma.
AB  - BACKGROUND: The aim of this study was to evaluate the prevalence of chromosome 8q
      gain in clear cell renal cell carcinoma (CCRCC) and to correlate the findings
      with tumor phenotype and disease-specific survival (DSS). METHODS: The tumor
      karyotypes of 336 consecutive patients with CCRCC were prospectively evaluated
      with classical cytogenetic analysis. Chromosome 8q status was correlated with
      clinicopathological variables, and its impact on DSS was evaluated. RESULTS: Gain
      of 8q occurred in 28 tumors (8.3%). Gain of 8q was associated with a higher risk
      of regional lymph node (21.4% vs 6.2%, P = .011) and distant metastases (50.0% vs
      24.4%, P = .006), and greater tumor sizes (P = .030). Patients with gain of 8q
      had a 3.22-fold increased risk of death from CCRCC (P < .001). In multivariable
      analysis, gain of 8q was identified as an independent prognostic factor (hazard
      ratio, 2.37; P = .006). The concordance index of a multivariable base model
      increased significantly following inclusion of 8q gain (P = .0015). CONCLUSIONS:
      Gain of chromosome 8q occurs in a subset of CCRCCs and is associated with an
      increased risk of metastases and death from CCRCC. Because the proto-oncogene c
      MYC is among the list of candidate genes located on 8q, our data suggest that
      these tumors may have unique pathways activated, which are associated with an
      aggressive tumor phenotype. If confirmed, defining tumors with gain of 8q may
      assist in identifying patients who would benefit for specific c-MYC inhibitors or
      agents that target the MAPK/ERK (mitogen-activated protein kinase) pathway.

PMID- 22605479
TI  - Efficient synthesis of sterically-stabilized nano-objects via RAFT dispersion
      polymerization of benzyl methacrylate in alcoholic media.
AB  - Synthesis of diblock copolymer nano-objects: alcohol is a good idea! RAFT
      dispersion polymerization of benzyl methacrylate in alcohol using weak
      polyelectrolyte-based chain transfer agents allows the facile synthesis of
      sterically stabilized diblock copolymer nano-objects with very high monomer
      conversions. Such syntheses are usually problematic when conducted in water due
      to electrostatic repulsion between highly charged stabilizer chains, which
      impedes in situ self-assembly. Construction of a detailed phase diagram
      facilitates reproducible syntheses of well-defined diblock copolymer spheres,
      worms or vesicles, since it allows mixed phase regions to be avoided. Aqueous
      electrophoresis studies confirm that these nano-objects can acquire substantial
      surface charge when transferred to aqueous solution due to ionization (or
      protonation) of the polyacid (or polybase) stabilizer chains.

PMID- 22605480
TI  - Natural killer T cell deficiency in active adult-onset Still's Disease:
      correlation of deficiency of natural killer T cells with dysfunction of natural
      killer cells.
AB  - OBJECTIVE: To examine the levels and functions of natural killer (NK) and natural
      killer T (NKT) cells, investigate relationships between NK and NKT cells, and
      determine the clinical relevance of NKT cell levels in patients with adult-onset
      Still's disease (AOSD). METHODS: Patients with active untreated AOSD (n = 20) and
      age- and sex-matched healthy controls (n = 20) were studied. NK and NKT cell
      levels were measured by flow cytometry. Peripheral blood mononuclear cells were
      cultured in vitro with alpha-galactosylceramide (alphaGalCer). NK cytotoxicity
      against K562 cells and proliferation indices of NKT cells were estimated by flow
      cytometry. RESULTS: Percentages and absolute numbers of NKT cells were
      significantly lower in the peripheral blood of AOSD patients than in that of
      healthy controls. Proliferative responses of NKT cells to alphaGalCer were also
      lower in patients, and this was found to be due to proinflammatory cytokines and
      NKT cell apoptosis. In addition, NK cytotoxicity was found to be significantly
      lower in patients than in healthy controls, but NK cell levels were comparable in
      the 2 groups. Notably, this NKT cell deficiency was found to be correlated with
      NK cell dysfunction and to reflect active disease status. Furthermore,
      alphaGalCer-mediated NK cytotoxicity, showing the interaction between NK and NKT
      cells, was significantly lower in AOSD patients than in healthy controls.
      CONCLUSION: These findings demonstrate that NK and NKT cell functions are
      defective in AOSD patients and suggest that these abnormalities contribute to
      innate immune dysfunction in AOSD.

PMID- 22605481
TI  - Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells
      to neural cells contributes to neurite outgrowth.
AB  - Multipotent mesenchymal stromal cells (MSCs) have potential therapeutic benefit
      for the treatment of neurological diseases and injury. MSCs interact with and
      alter brain parenchymal cells by direct cell-cell communication and/or by
      indirect secretion of factors and thereby promote functional recovery. In this
      study, we found that MSC treatment of rats subjected to middle cerebral artery
      occlusion (MCAo) significantly increased microRNA 133b (miR-133b) level in the
      ipsilateral hemisphere. In vitro, miR-133b levels in MSCs and in their exosomes
      increased after MSCs were exposed to ipsilateral ischemic tissue extracts from
      rats subjected to MCAo. miR-133b levels were also increased in primary cultured
      neurons and astrocytes treated with the exosome-enriched fractions released from
      these MSCs. Knockdown of miR-133b in MSCs confirmed that the increased miR-133b
      level in astrocytes is attributed to their transfer from MSCs. Further
      verification of this exosome-mediated intercellular communication was performed
      using a cel-miR-67 luciferase reporter system and an MSC-astrocyte coculture
      model. Cel-miR-67 in MSCs was transferred to astrocytes via exosomes between 50
      and 100 nm in diameter. Our data suggest that the cel-miR-67 released from MSCs
      was primarily contained in exosomes. A gap junction intercellular communication
      inhibitor arrested the exosomal microRNA communication by inhibiting exosome
      release. Cultured neurons treated with exosome-enriched fractions from MSCs
      exposed to 72 hours post-MCAo brain extracts significantly increased the neurite
      branch number and total neurite length. This study provides the first
      demonstration that MSCs communicate with brain parenchymal cells and may regulate
      neurite outgrowth by transfer of miR-133b to neural cells via exosomes.

PMID- 22605483
TI  - Catenated PS-PMMA block copolymers via supramolecularly templated ATRP initiator
      approach.
AB  - A novel route to synthesize catenated macrocyclic PS-PMMA block copolymers is
      demonstrated via combination of supramolecular chemistry and controlled radical
      polymerization (CRP). Polymerization of styrene with bromopropionate ester
      initiator coupled with phenanthroline Cu(I) complex affords a four arm PS
      macroinitiator, which upon further chain extension by polymerization of MMA
      generates a four arm PS-PMMA block copolymer. Intramolecular coupling of PS-PMMA
      Br arms via low temperature styrene-assisted atom transfer radical coupling
      (ATRC) leads to the formation of PS-PMMA catenand, which generates the metal-free
      catenated macrocyclic PS-PMMA block copolymer after removal of Cu metal. The
      interlocked structures of catenated block copolymers are confirmed by GPC, NMR,
      and AFM image analysis.

PMID- 22605482
TI  - Crosstalk between the hepatologist and the cardiologist: a future place for the
      lithocholic acid as a coronary atheroma risk factor?

PMID- 22605490
TI  - Nanosheet-constructed porous TiO2-B for advanced lithium ion batteries.
AB  - Hierarchical porous TiO(2)-B with thin nanosheets is successfully synthesized.
      TiO(2)-B polymorph ensures fast insertion of Li-ion due to its pseudocapacitive
      mechanism. The thin nanosheet walls with porous structure allow exposure to
      electrolytes for facile ionic transport and interfacial reaction. The joint
      advantages endow this material with high reversible capacity, excellent cycling
      performance, and superior rate capability.

PMID- 22605491
TI  - Dissolved organic matter reduces algal accumulation of methylmercury.
AB  - Dissolved organic matter (DOM) significantly decreased accumulation of
      methylmercury (MeHg) by the diatom Cyclotella meneghiniana in laboratory
      experiments. Live diatom cells accumulated two to four times more MeHg than dead
      cells, indicating that accumulation may be partially an energy-requiring process.
      Methylmercury enrichment in diatoms relative to ambient water was measured by a
      volume concentration factor (VCF). Without added DOM, the maximum VCF was 32 *
      10(4) , and the average VCF (from 10 to 72 h) over all experiments was 12.6 *
      10(4) . At very low (1.5 mg/L) added DOM, VCFs dropped by approximately half. At
      very high (20 mg/L) added DOM, VCFs dropped 10-fold. Presumably, MeHg was bound
      to a variety of reduced sulfur sites on the DOM, making it unavailable for
      uptake. Diatoms accumulated significantly more MeHg when exposed to transphilic
      DOM extracts than hydrophobic ones. However, algal lysate, a labile type of DOM
      created by resuspending a marine diatom in freshwater, behaved similarly to a
      refractory DOM isolate from San Francisco Bay. Addition of 67 uM L-cysteine
      resulted in the largest drop in VCFs, to 0.28 * 10(4) . Although the DOM
      composition influenced the availability of MeHg to some extent, total DOM
      concentration was the most important factor in determining algal bioaccumulation
      of MeHg.

PMID- 22605506
TI  - Molecular level ordering in poly(2-vinylpyridine).
AB  - The reaction between atactic poly(2-vinylpyridine) and 1,4-dibromobutane leads to
      formation of long-range 3D molecular ordering in polymer chains mainly because
      the side group (pyridine) of the polymer chain changes to a syndotactic
      configuration. This may enable the production of functional molecular devices
      that operate on a 3D atomic scale.

PMID- 22605504
TI  - Tumor response assessment by modified Choi criteria in localized high-risk soft
      tissue sarcoma treated with chemotherapy.
AB  - BACKGROUND: The objective of this study was to compare the prognostic relevance
      of Response Evaluation Criteria in Solid Tumors (RECIST) versus Choi criteria for
      the assessment of response in patients with high-risk soft tissue sarcoma of the
      extremities or trunk wall who received preoperative chemotherapy with or without
      radiotherapy in a phase 3 trial. METHODS: Patients received 3 cycles of
      preoperative epirubicin + ifosfamide with or without radiotherapy. The diagnostic
      concordance between RECIST and Choi criteria and their correlation with overall
      survival (OS) and freedom from progression (FFP) were evaluated in a univariate
      Cox regression model. RESULTS: In 243 of 321 eligible patients, RECIST, Choi
      criteria, and histology were predictive for OS and FFP. In the subgroup of 69
      patients who received chemotherapy alone and were evaluable by both RECIST and
      Choi criteria, Choi criteria were associated significantly with OS and FFP,
      whereas RECIST predicted only FFP, and the pattern of agreement observed between
      the 2 criteria was unsatisfactory. On a dichotomous scale, comparing objective
      response (complete and partial responses) and lack of response (stable and
      progressive disease) to preoperative chemotherapy according to RECIST and Choi
      criteria, only Choi criteria were predictive of OS and FFP, and fair agreement
      between RECIST and Choi criteria was observed. When lack of progression and
      progression were compared (complete and partial responses + stable disease vs
      progressive disease), both assessment criteria were significantly predictive of
      OS and FFP, and there was substantial agreement between the 2 criteria.
      CONCLUSIONS: Response to chemotherapy with or without radiotherapy was associated
      with a better outcome in patients with high-risk soft tissue sarcoma. Choi
      criteria were better predictors than RECIST in patients who received preoperative
      chemotherapy alone.

PMID- 22605507
TI  - Bayesian approach to potency estimation for aquatic toxicology experiments when a
      toxicant affects both fecundity and survival.
AB  - Chemicals in aquatic systems may impact a variety of endpoints including
      mortality, growth, or reproduction. Clearly, growth or reproduction will only be
      observed in organisms that survive. Because it is common to observe mortality in
      studies focusing on the reproduction of organisms, especially in higher
      concentration conditions, the resulting observed numbers of young become a
      mixture of zeroes and positive counts. Zeroes are recorded for organisms that die
      before having any young and living organisms with no offspring. Positive counts
      are recorded for living organisms with offspring. Thus, responses reflect both
      fecundity and mortality of the organisms used in such tests. In the present
      study, the authors propose the estimation of the concentration associated with a
      specified level of reproductive inhibition (RIp) using a Bayesian zero-inflated
      Poisson (ZIP) regression model. This approach allows any prior information and
      expert knowledge about the model parameters to be incorporated into the
      regression coefficients or RIp estimation. Simulation studies are conducted to
      compare the Bayesian ZIP regression model and classical methods. The Bayesian
      estimator outperforms the frequentist alternative by producing more precise point
      estimates with smaller mean square differences between RIp estimates and true
      values, narrower interval estimates with better coverage probabilities. The
      authors also applied their proposed model to a study of Ceriodaphnia dubia
      exposed to a test toxicant.

PMID- 22605508
TI  - Hedgehog-responsive progenitors: predictors of liver outcomes?

PMID- 22605509
TI  - Fractures among long-term survivors of childhood cancer: a report from the
      Childhood Cancer Survivor Study.
AB  - BACKGROUND: Although reductions in bone mineral density are well documented among
      children during treatment for cancer and among childhood cancer survivors, little
      is known about the long-term risk of fracture. The objective of this study was to
      ascertain the prevalence of and risk factors for fractures among individuals
      participating in the Childhood Cancer Survivor Study (CCSS). METHODS: Analyses
      included 7414 >= 5-year survivors of childhood cancer diagnosed between 1970 and
      1986 who completed the 2007 CCSS follow-up questionnaire and a comparison group
      of 2374 siblings. Generalized linear models stratified by sex were used to
      compare the prevalence of reported fractures between survivors and siblings.
      RESULTS: The median ages at follow-up among survivors and siblings were 36.2
      years (range, 21.2-58.8 years) and 38.1 years (range, 18.4-62.6 years),
      respectively, with a median 22.7 years of follow-up after cancer diagnosis for
      survivors. Approximately 35% of survivors and 39% of siblings reported >= 1
      fracture during their lifetime. The prevalence of fractures was lower among
      survivors than among siblings, both in males (prevalence ratio, 0.87; 95%
      confidence interval, 0.81-0.94; P < .001) and females (prevalence ratio, 0.94;
      95% confidence interval, 0.86-1.04; P = .22). In multivariable analyses,
      increasing age at follow-up, white race, methotrexate treatment, and balance
      difficulties were associated with increased prevalence of fractures among female
      survivors (P = .015). Among males, only smoking history and white race were
      associated with an increased prevalence of fracture (P < .001). CONCLUSIONS:
      Findings from this study indicated that the prevalence of fractures among adult
      survivors did not increase compared with that of siblings. Additional studies of
      bone health among aging female cancer survivors may be warranted.

PMID- 22605511
TI  - Do pocket-sized ultrasound machines have the potential to be used as a tool to
      triage patients in obstetrics and gynecology?
AB  - OBJECTIVES: To evaluate the performance and potential impact on patient
      management of a pocket-sized ultrasound machine (PUM) in comparison to high
      specification ultrasound machines (HSUM). METHODS: This was an observational
      cohort study with 204 unselected patients in three categories: 1) women with pain
      and bleeding in early pregnancy (101 patients); 2) women presenting for routine
      obstetric ultrasound assessment (53 patients); 3) women with possible
      gynecological pathology (50 patients). Scans were carried out transabdominally
      using a PUM. A second operator repeated the examination transvaginally and/or
      transabdominally, depending on the clinical indication, using an HSUM. The
      operators were blind to each other's findings. RESULTS: In the early pregnancy
      group, there was good to very good agreement between the PUM and HSUM for
      identifying the presence or absence of an embryo, gestational sac, fetal heart
      motion, pregnancy location and final diagnostic outcome (kappa coefficients,
      0.844, 0.843, 0.729, 0.785 and 0.812, respectively; P < 0.0001). In the obstetric
      ultrasound group there was good to very good agreement for fetal presentation,
      placental location and placental position (kappa coefficients, 0.924, 0.924 and
      0.647, respectively; P < 0.0001). In the gynecological pathology group, there was
      very good agreement for final diagnosis and type of ovarian mass (low risk or
      complex) (kappa coefficients, 0.846 and 0.930, respectively; P < 0.0001). For the
      measured continuous variables, there was close agreement for crown-rump length,
      mean sac diameter, femur length and mean diameter of an ovarian mass, but not for
      endometrial thickness. Neither patient demographics (age, body mass index,
      ethnicity) nor operator experience and familiarity with a PUM had an impact on
      agreement between the two machines. If a PUM had been the only equipment
      available for an initial assessment, only two cases would have led to a
      suboptimal patient management plan. CONCLUSION: The findings and final diagnosis
      in the three study groups were similar for both a PUM used transabdominally and
      an HSUM used transvaginally and/or transabdominally.

PMID- 22605513
TI  - Generation and external validation of a tumor-derived 5-gene prognostic signature
      for recurrence of lymph node-negative, invasive colorectal carcinoma.
AB  - BACKGROUND: One in 4 patients with lymph node-negative, invasive colorectal
      carcinoma (CRC) develops recurrent disease after undergoing curative surgery, and
      most die of advanced disease. Predicting which patients will develop a recurrence
      is a significantly growing, unmet medical need. METHODS: Archival formalin-fixed,
      paraffin-embedded (FFPE) primary adenocarcinoma tissues obtained at surgery were
      retrieved from 74 patients with CRC (15 with stage I disease and 59 with stage II
      disease) for Training/Test Sets. In addition, FFPE tissues were retrieved from 49
      patients with stage I CRC and 215 patients with stage II colon cancer for an
      External Validation (EV) Set (n = 264) from 18 hospitals in 4 countries. No
      patients had received neoadjuvant/adjuvant therapy. Proprietary genetic
      programming analysis of expression profiles for 225 prespecified tumor genes was
      used to create a 36-month recurrence risk signature. RESULTS: Using reverse
      transcriptase-polymerase chain reaction, a 5-gene rule correctly classified 62 of
      92 recurrent patients and 87 of 172 nonrecurrent patients in the EV Set
      (sensitivity, 0.67; specificity, 0.51). "High-risk" patients had a greater
      probability of 36-month recurrence (42%) than "low-risk" patients (26%; hazard
      ratio, 1.80; 95% confidence interval, 1.19-2.71; P = .007; Cox regression)
      independent of T-classification, the number of lymph nodes examined, histologic
      grade/subtype, anatomic location, age, sex, or race. The rule outperformed (P =
      .021) current National Comprehensive Cancer Network Guidelines (hazard ratio,
      0.897). The same rule also differentiated the risk of recurrence (hazard ratio,
      1.63; P = .031) in a subset of patients from the EV Set who had stage I/II colon
      cancer only (n = 251). CONCLUSIONS: To the authors' knowledge, the 5-gene rule
      (OncoDefender-CRC) is the first molecular prognostic that has been validated in
      both stage I CRC and stage II colon cancer. It outperforms standard
      clinicopathologic prognostic criteria and obviates the need to retrieve >=12
      lymph nodes for accurate prognostication. It identifies those patients most
      likely to develop recurrent disease within 3 years after curative surgery and,
      thus, those most likely to benefit from adjuvant treatment.

PMID- 22605514
TI  - To FRAX or not to FRAX.

PMID- 22605515
TI  - Vertebral fracture and intervertebral discs.

PMID- 22605517
TI  - Anticytomegalovirus seropositivity in rheumatoid arthritis is not associated with
      the presence of severe extraarticular complications: comment on the article by
      Pierer et al.

PMID- 22605518
TI  - Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not
      reflected by radiographic indicators.
AB  - BACKGROUND: Experience with preoperative therapy for other cancers has led to an
      assumption that borderline resectable pancreatic cancers can be converted to
      resectable cancers with preoperative therapy. In this study, the authors sought
      to determine the rate at which neoadjuvant therapy is associated with a reduction
      in the size or stage of borderline resectable tumors. METHODS: Patients who had
      borderline resectable pancreatic cancer and received neoadjuvant therapy before
      potentially undergoing surgery at the authors' institution between 2005 and 2010
      were identified. The patients' pretreatment and post-treatment pancreatic
      protocol computed tomography images were rereviewed to determine changes in tumor
      size or stage using modified Response Evaluation Criteria in Solid Tumors
      (RECIST) (version 1.1) and standardized anatomic criteria. RESULTS: The authors
      identified 129 patients who met inclusion criteria. Of the 122 patients who had
      their disease restaged after receiving preoperative therapy, 84 patients (69%)
      had stable disease, 15 patients (12%) had a partial response to therapy, and 23
      patients (19%) had progressive disease. Although only 1 patient (0.8%) had their
      disease downstaged to resectable status after receiving neoadjuvant therapy, 85
      patients (66%) underwent pancreatectomy. The median overall survival duration for
      all 129 patients was 22 months (95% confidence interval, 14-30 months). The
      median overall survival duration for the patients who underwent pancreatectomy
      was 33 months (95% confidence interval, 25-41 months) and was not associated with
      RECIST response (P = .78). CONCLUSIONS: Radiographic downstaging was rare after
      neoadjuvant therapy, and RECIST response was not an effective treatment endpoint
      for patients with borderline resectable pancreatic cancer. The authors concluded
      that these patients should undergo pancreatectomy after initial therapy in the
      absence of metastases.

PMID- 22605519
TI  - Prospective validation of fetal weight estimation using fractional limb volume.
AB  - OBJECTIVES: To prospectively validate the use of fractional limb volume
      measurements for estimated fetal weight (EFW) during the second and third
      trimesters of pregnancy and to summarize the medical literature regarding
      application of fractional limb volume for fetal weight estimation. METHODS: One
      hundred and sixty-four women prospectively underwent three-dimensional
      ultrasonography within 4 days of delivery. Birth weights (BWs) ranged from 390 to
      5426 g. Fetal measurements were extracted using volume datasets for biparietal
      diameter, abdominal circumference, femur diaphysis length, fractional arm volume
      and fractional thigh volume. Fractional limb volumes were manually traced from a
      central portion of the humerus or femur diaphysis. Mean percentage differences
      and SDs of the percentage differences were calculated for EFW. The proportion of
      newborns with EFW within 5 or 10% of BW were compared with an estimate obtained
      using a Hadlock formula that was modified using model coefficients from the same
      local population sample. RESULTS: Ultrasound scans were performed between 21.7
      and 42 weeks' menstrual age. Optimal model performance (1.9 +/- 6.6%) resulted
      from using a combination of biparietal diameter, abdominal circumference and
      fractional thigh volume. The precision of this model was superior to results
      obtained using a modified Hadlock model (1.1 +/- 8.4%), although accuracy of
      these predictions was slightly decreased for female infants. For all fetuses, the
      prediction model that incorporated fractional thigh volume correctly classified a
      greater proportion of EFW within 5% (55.1 vs 43.7%; P = 0.03) or 10% (86.5 vs
      75.9%; P < 0.05) of BW when compared with the modified Hadlock model.
      CONCLUSIONS: Fractional thigh volume can be added to two-dimensional sonographic
      measurements of the head and trunk to improve the precision of fetal weight
      estimation. This approach permits the inclusion of soft tissue development as
      part of a weight estimation procedure for the assessment of generalized fetal
      nutritional status.

PMID- 22605523
TI  - Electronic family health history records draw attention: proposed federal
      regulation and new tool emphasize digital conversion.

PMID- 22605520
TI  - SCA6 presenting with young-onset parkinsonism without ataxia.

PMID- 22605524
TI  - At $1,000, is genomic sequencing clinically useful in newborns?: many key
      questions remain unanswered.

PMID- 22605526
TI  - Agroecosystems and primate conservation in the tropics: a review.
AB  - Agroecosystems cover more than one quarter of the global land area (ca. 50
      million km(2) ) as highly simplified (e.g. pasturelands) or more complex systems
      (e.g. polycultures and agroforestry systems) with the capacity to support higher
      biodiversity. Increasingly more information has been published about primates in
      agroecosystems but a general synthesis of the diversity of agroecosystems that
      primates use or which primate taxa are able to persist in these anthropogenic
      components of the landscapes is still lacking. Because of the continued extensive
      transformation of primate habitat into human-modified landscapes, it is important
      to explore the extent to which agroecosystems are used by primates. In this
      article, we reviewed published information on the use of agroecosystems by
      primates in habitat countries and also discuss the potential costs and benefits
      to human and nonhuman primates of primate use of agroecosystems. The review
      showed that 57 primate taxa from four regions: Mesoamerica, South America, Sub
      Saharan Africa (including Madagascar), and South East Asia, used 38 types of
      agroecosystems as temporary or permanent habitats. Fifty-one percent of the taxa
      recorded in agroecosystems were classified as least concern in the IUCN Red List,
      but the rest were classified as endangered (20%), vulnerable (18%), near
      threatened (9%), or critically endangered (2%). The large proportion of
      threatened primates in agroecosystems suggests that agroecosystems may play an
      important role in landscape approaches to primate conservation. We conclude by
      discussing the value of agroecosystems for primate conservation at a broad scale
      and highlight priorities for future research.

PMID- 22605527
TI  - Effects of equine joint injury on boundary lubrication of articular cartilage by
      synovial fluid: role of hyaluronan.
AB  - OBJECTIVE: To compare equine synovial fluid (SF) from injured and control joints
      for cartilage boundary lubrication function; concentrations of the putative
      boundary lubricant molecules hyaluronan (HA), proteoglycan 4 (PRG4), and surface
      active phospholipids (SAPLs); relationships between lubrication function and
      composition; and lubrication restoration by addition of HA. METHODS: Equine SF
      from normal joints, joints with acute injury, and joints with chronic injury were
      analyzed for boundary lubrication of normal articular cartilage (kinetic friction
      coefficient [MU(kinetic) ]). Equine SF samples were analyzed for HA, PRG4, and
      SAPL concentrations and HA molecular weight distribution. The effect of the
      addition of HA, of different concentrations and molecular weight, on the
      MU(kinetic)  of equine SF samples from normal joints and joints with acute injury
      was determined. RESULTS: The MU(kinetic)  of equine SF from joints with acute
      injury (0.036) was higher (+39%) than that of equine SF from normal joints
      (0.026). Compared to normal equine SF, SF from joints with acute injury had a
      lower HA concentration (-30%) of lower molecular weight forms, higher PRG4
      concentration (+83%), and higher SAPL concentration (+144%). Equine SF from
      joints with chronic injury had MU(kinetic) , PRG4, and SAPL characteristics
      intermediate to those of equine SF from joints with acute injury and normal
      equine SF. Regression analysis revealed that the MU(kinetic)  value decreased
      with increasing HA concentration in equine SF. The friction-reducing properties
      of HA alone improved with increasing concentration and molecular weight. The
      addition of high molecular weight HA (4,000 kd) to equine SF from joints with
      acute injury reduced the MU(kinetic)  to a value near that of normal equine SF.
      CONCLUSION: In the acute postinjury stage, equine SF exhibits poor boundary
      lubrication properties, as indicated by a high MU(kinetic) . HA of diminished
      concentration and molecular weight may be the basis for this, and adding HA to
      deficient equine SF restored lubrication function.

PMID- 22605528
TI  - Automatic segmentation of cell nuclei in Feulgen-stained histological sections of
      prostate cancer and quantitative evaluation of segmentation results.
AB  - Digital image analysis of cell nuclei is useful to obtain quantitative
      information for the diagnosis and prognosis of cancer. However, the lack of a
      reliable automatic nuclear segmentation is a limiting factor for high-throughput
      nuclear image analysis. We have developed a method for automatic segmentation of
      nuclei in Feulgen-stained histological sections of prostate cancer. A local
      adaptive thresholding with an object perimeter gradient verification step
      detected the nuclei and was combined with an active contour model that featured
      an optimized initialization and worked within a restricted region to improve
      convergence of the segmentation of each nucleus. The method was tested on 30
      randomly selected image frames from three cases, comparing the results from the
      automatic algorithm to a manual delineation of 924 nuclei. The automatic method
      segmented a few more nuclei compared to the manual method, and about 73% of the
      manually segmented nuclei were also segmented by the automatic method. For each
      nucleus segmented both manually and automatically, the accuracy (i.e., agreement
      with manual delineation) was estimated. The mean segmentation
      sensitivity/specificity were 95%/96%. The results from the automatic method were
      not significantly different from the ground truth provided by manual
      segmentation. This opens the possibility for large-scale nuclear analysis based
      on automatic segmentation of nuclei in Feulgen-stained histological sections.

PMID- 22605529
TI  - New world monkey nightmares: science, art, use, and abuse (?) in platyrrhine
      taxonomic nomenclature.
AB  - The taxonomy and nomenclature of New World monkeys is becoming precariously
      unstable and impractical, plagued by revisions aimed at conforming to approaches
      that reject the Biological Species Concept for narrowly construed reasons and
      resulting in a hyperinflated taxonomy at species (often) and genus (sometimes)
      levels. This undermines a major goal of classification at the most basic
      taxonomic levels to ease communication and facilitate research. Since it is
      difficult to justify extensive changes in terminology without a deeply justified
      theoretical purpose or without showing what scientific benefits these alterations
      can bring, working primatologists need not accept this doctrinaire trend. Knowing
      as little as we do about what a species actually is, does not justify contorting
      the value of a species nomenclature so that it reflects nothing more than coat
      color, a node, or endpoint of a dendrogram.

PMID- 22605531
TI  - Prenatal diagnosis of isolated total anomalous pulmonary venous connection: a
      series of 10 cases.
AB  - OBJECTIVES: To report on a series of 10 fetuses with prenatally diagnosed
      isolated total anomalous pulmonary venous connection (TAPVC), focusing on
      echocardiographic features leading to diagnosis, assess accuracy of prenatal
      diagnosis and describe postnatal outcome. METHODS: In this review of our
      experience of prenatal diagnosis of isolated TAPVC, we analyzed retrospectively
      medical records and fetal echocardiography findings in all cases with prenatal
      diagnosis of isolated TAPVC delivered between 1 January 2001 and 1 October 2011
      at a tertiary referral center, paying special attention to echocardiographic
      signs that led to referral. RESULTS: During the study period, 95 infants with
      isolated TAPVC were seen at the center. Initially, expert fetal echocardiography
      identified 14 fetuses with isolated TAPVC. Prenatal diagnosis was made at a mean
      gestational age of 31 (range, 25-37) weeks. Ten true-positive cases of TAPVC were
      confirmed after birth. The remaining four were considered false-positive cases:
      two had normal heart with left superior vena cava to coronary sinus, one had
      partial anomalous venous connection and one was lost to follow-up. Of the 85
      diagnosed postnatally with TAPVC, only one had been seen prenatally by an expert
      cardiac sonographer. Echocardiographic signs leading to referral were related to
      pulmonary venous connection in half of the cases. Other suspected defects which
      led to referral were ostium prium atrial defect (n = 3), left-right asymmetry (n
      = 1), abnormal mitral valve (n = 1) and hepatic vascular malformation (n = 1).
      All infants with TAPVC underwent surgery. There was one postoperative death and
      nine survivors, with a mean follow-up of 31 (range, 2-104) months. CONCLUSION:
      Fetal diagnosis of isolated TAPVC is challenging even for experts.
      Echocardiographic anomalies may appear late in gestation. New tools should be
      proposed to identify abnormal venous drainage at the screening level.

PMID- 22605530
TI  - Driver mutations determine survival in smokers and never-smokers with stage
      IIIB/IV lung adenocarcinomas.
AB  - BACKGROUND: The authors previously demonstrated that never-smokers with stage
      IIIB/IV nonsmall cell lung cancer (NSCLC) lived 50% longer than former/current
      smokers. This observation persisted after adjusting for age, performance status,
      and sex. In this study, the authors hypothesized that smoking-dependent
      differences in the distribution of driver mutations may explain differences in
      prognosis between these subgroups. METHODS: In total, 293 never-smokers and 382
      former/current smokers with lung adenocarcinoma who underwent testing for
      epidermal growth factor receptor (EGFR) mutations and v-Ki-ras2 Kirsten rat
      sarcoma viral oncogene homolog (KRAS) mutations and rearrangements in anaplastic
      lymphoma kinase (ALK) between 2009 and 2010 were investigated. Clinical outcomes
      and patient characteristics were collected. Survival probabilities were estimated
      using the Kaplan-Meier method. Group comparison was performed with log-rank tests
      and Cox proportional hazards methods. RESULTS: Although the overall incidence of
      these mutations was nearly identical (55% never-smokers vs 57% current/former
      smokers; P = .48), there were significant differences in the distribution of
      mutations between these groups for EGFR mutations (37% never-smokers vs 14%
      former/current smokers; P < .0001), KRAS mutations (4% never-smokers vs 43%
      former/current smokers; P < .0001), and ALK rearrangements (12% never-smokers vs
      2% former/current smokers; P < .0001). Among never-smokers and former/current
      smokers, the prognosis differed significantly by genotype. Patients who had KRAS
      mutations had the poorest survival. Smoking status, however, had no influence on
      survival within each genotype. CONCLUSIONS: Never-smokers and former/current
      smokers with lung adenocarcinomas were not homogeneous subgroups. Each was made
      up of individuals whose tumors had a unique distribution of driver mutations,
      which were associated with different prognoses, irrespective of smoking history.

PMID- 22605532
TI  - A clinically relevant benefit of statins in young patients with systemic lupus
      erythematosus cannot be excluded: comment on the article by Schanberg et al.

PMID- 22605533
TI  - Drug testing in the workplace.
AB  - Congress passed the Drug-Free Workplace Act in April 1988, which resulted in the
      Mandatory Guidelines for Federal Workplace Drug Testing Programs. The intent was
      to establish a substance-free work environment for all federal workers by
      requiring that all federal employees pass a urine drug test before employment.
      These guidelines specifically, and exclusively, focus on testing urine specimens
      for metabolites of marijuana, cocaine, phencyclidine, opiates (focusing on heroin
      metabolites), and amphetamines (including Ecstasy). Since then, there have been
      many scientific, technical, and legal challenges to the validity of urine drug
      testing. In response, the Substance Abuse and Mental Health Services
      Administration, a division operating under the executive branch of the United
      States Department of Health and Human Services, put forth, through many
      revisions, strict procedural guidelines and specimen validity-testing criteria to
      manage suspicious or adulterated samples during and after urine collection. This
      review focuses on the legal ramifications, the procedural process, and the
      sensitivity and specificity of the two urine drug tests used for workplace drug
      testing: immunoassay and gas chromatography-mass spectrometry. Moreover, we
      dissect the problematic issue of cross-sensitivity between illicit and
      prescription drugs, and how this affects the validity of future urine drug
      testing.

PMID- 22605534
TI  - Ovarian stromal vessels assessed by spatiotemporal image correlation-high
      definition flow in women with polycystic ovary syndrome: a case-control study.
AB  - OBJECTIVE: To compare spatiotemporal image correlation-high definition flow (STIC
      HDF) indices from spherical samples of ovary between women with polycystic ovary
      syndrome (PCOS) and normal women. METHODS: This was a prospective case-control
      study of premenopausal women with a diagnosis of PCOS according to the Rotterdam
      criteria and of healthy, regularly menstruating, premenopausal women (controls)
      matched for age (< 35 years) and body mass index. Women were assessed in the
      follicular phase of the menstrual cycle by 4D STIC-HDF transvaginal ultrasound.
      Based on 1-cm(3) spherical sampling, we calculated for each woman the
      vascularization index (VI) for the most vascularized part of the ovarian stroma
      in all three-dimensional volumes of the 4D STIC-HDF sequence. The maximum
      (VI(sys)) and minimum (VI(diast)) values were assumed to represent systole and
      diastole, respectively, and the mean VI for all frames from one cardiac cycle was
      calculated. Based on these three VI values, we calculated the following indices:
      volumetric systolic/diastolic ratio (vS/D), volumetric resistance index (vRI) and
      volumetric pulsatility index (vPI), and compared them between study and control
      groups. RESULTS: The study included 32 PCOS women (mean age, 29.6 years) and 32
      controls (mean age, 30.4 years). Mean VI(sys) (26.246% vs 8.136%, P < 0.0001) and
      mean VI(diast) (22.242% vs 5.997%, P < 0.0001) were significantly higher in PCOS
      women compared with controls. Median vS/D (1.15 vs 1.33, P < 0.001), mean vRI
      (0.17 vs 0.30, P < 0.001) and median vPI (0.14 vs 0.28, P < 0.001) were
      significantly lower in PCOS women compared with controls. CONCLUSION: 4D STIC-HDF
      indices from 1-cm(3) spherical samples of the ovaries were different between PCOS
      women and controls, suggesting lower impedance to flow in ovarian stromal vessels
      in PCOS women.

PMID- 22605535
TI  - Training a hospitalist workforce to address the intensivist shortage in American
      hospitals: a position paper from the Society of Hospital Medicine and the Society
      of Critical Care Medicine.

PMID- 22605536
TI  - Clinical implications for cannabinoid use in the rheumatic diseases: potential
      for help or harm?

PMID- 22605537
TI  - Cardiac denervation precedes nigrostriatal damage in idiopathic rapid eye
      movement sleep behavior disorder.

PMID- 22605538
TI  - Incidence of amiodarone hypersensitivity in patients with previous allergy to
      iodine or iodinated contrast agents.
AB  - STUDY OBJECTIVE: To determine the incidence and nature of allergic reactions to
      amiodarone in hospitalized patients with a listed allergy to iodine or iodinated
      radiocontrast agents. DESIGN: Retrospective medical record review. SETTING: Two
      academic medical centers. PATIENTS: A total of 234 sequential hospitalized
      patients with a listed iodine and/or iodinated radiocontrast agent allergy who
      received oral or intravenous amiodarone between January 2006 and December 2010.
      MEASUREMENTS AND MAIN RESULTS: Demographic and clinical data, as well as
      documentation of an allergic reaction to amiodarone, were collected for each
      patient from electronic medical records. Mean +/- SD age was 69 +/- 12 years, and
      51% were male. Of the 234 patients, 167 (71%) had a listed previous allergy to
      iodinated contrast agents, 55 (24%) to iodine, and 12 (5%) to both. Patients
      received an average inpatient total dose of 2.9 +/- 3.2 g of either oral (106
      patients [45%]), intravenous (39 patients [17%]), or both oral and intravenous
      (89 patients [38%]) amiodarone. Only 1 (0.4%) of the 234 patients was identified
      as having a probable allergic reaction to amiodarone (score of 6 on the Naranjo
      adverse drug reaction probability scale). One additional patient receiving
      intravenous amiodarone experienced a rash that was determined to be caused by an
      antibiotic. All other patients received amiodarone without any identifiable
      allergic reactions. CONCLUSION: The incidence of hypersensitivity reaction to
      amiodarone in hospitalized patients with a listed allergy to iodine or iodinated
      contrast agents was less than 1%, and all identified reactions were without long
      term sequelae. Allergy to iodine and iodinated contrast agents may not be a valid
      absolute contraindication to amiodarone administration in the inpatient setting.

PMID- 22605539
TI  - A novel lenticular arena to quantify locomotor competence in walking fruit flies.
AB  - Drosophila melanogaster has become an important invertebrate model organism in
      biological and medical research, for mutational and genetic analysis, and in
      toxicological screening. Many screening assays have been developed that assess
      the flies' mortality, reproduction, development, morphology, or behavioral
      competence. In this study, we describe a new assay for locomotor competence. It
      comprises a circular walking arena with a lenticular floor and a flat cover (the
      slope of the floor increases gradually from the center to the edge of the arena)
      plus automated fly tracking and statistical analysis. This simple modification of
      a flat arena presents a graduated physical challenge, with which we can assess
      fine gradations of motor ability, since a fly's time average radial distance from
      the arena center is a direct indicator of its climbing ability. The time averaged
      distribution of flies as a function of slope, activity levels, and walking speed,
      yields a fine grained picture of locomotory ability and motivation levels. We
      demonstrate the strengths and weaknesses of this assay (compared with a
      conventional tap-down test) by observing flies treated with a neurotoxin (BMAA)
      that acts as a glutamate agonist. The assay proves well suited to detect dose
      effects and progression effects with higher statistical power than the
      traditional tap-down, but it has a higher detection limit, making it less
      sensitive to treatment effects.

PMID- 22605540
TI  - Hidden mortality of prenatally diagnosed vein of Galen aneurysmal malformation:
      retrospective study and review of the literature.
AB  - OBJECTIVE: To evaluate the prognosis of prenatally diagnosed vein of Galen
      aneurysmal malformation (VGAM) in a large cohort with this condition and to
      review the literature on prenatally diagnosed VGAM. METHODS: This was a
      retrospective study of all cases of prenatally diagnosed VGAM managed in our
      referral center during a 12-year period. VGAM was categorized as being either
      isolated or associated with any other abnormality, based on fetal ultrasound and
      magnetic resonance imaging findings. Poor outcomes comprised termination of
      pregnancy with confirmation of antenatal findings, perinatal death and severe
      cardiac and/or neurological impairment in survivors. The literature was also
      reviewed for similar cases. RESULTS: Twenty-one cases of prenatally diagnosed
      VGAM were managed in our center. Four (19.0%) cases were isolated and 17 (81.0%)
      were associated with other anomalies. There were nine terminations (42.9%) and
      six neonatal deaths (28.6%). Six children (28.6%) were still alive at last follow
      up, of whom three had abnormal neurological development. VGAM associated with
      other anomalies was strongly associated with a poor outcome compared with
      isolated forms (P < 0.0001). One hundred and nine cases from the literature were
      also reviewed. CONCLUSION: Fetuses with prenatally diagnosed VGAM have
      unexpectedly poor outcomes in the presence of cardiac or cerebral anomalies,
      while those with strictly isolated VGAM tend to have more favorable outcomes. Our
      literature review corroborates these findings.

PMID- 22605541
TI  - Protective role of systemic furin in immune response-induced arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune joint disease associated
      with chronic inflammation of the synovium that causes profound damage of joints.
      Inflammation results in part from the influx of immune cells secreting
      inflammatory cytokines and the reduction in the number of Treg cells. We
      undertook this study to assess the effect of furin, a proteinase implicated in
      the proteolytic activity of various precursor proteins and involved in the
      regulation of both proteinase maturation and immune cells, in an experimental
      model of RA. METHODS: The effect of furin and its inhibitor alpha1-PDX was tested
      in mice with collagen-induced arthritis (CIA). Joints were processed for
      histology and protein expression. Levels of cytokines were measured in joint
      tissue, and Treg cell numbers were measured in spleens. RESULTS: Furin expression
      and activity were high in the synovial pannus in RA patients and mice with CIA.
      Systemic administration of furin prevented increases in the arthritis score,
      joint destruction, and bone loss, in contrast to systemic administration of the
      furin inhibitor alpha1-PDX, which enhanced these parameters. By preventing the
      development of synovial pannus, furin reduced the expression of
      metalloproteinases in the joints. In contrast, alpha1-PDX enhanced synovial
      proliferation and the expression and activity of matrix metalloproteinases.
      Furthermore, furin reversed the local Th1/Th2 balance and restored the number of
      Treg cells in the spleen, indicating mediation by immune cells. CONCLUSION: These
      findings show the protective role of exogenous furin against RA, mediated by an
      immune response. The data suggest the potential therapeutic use of furin or its
      derivatives in autoimmune diseases including RA.

PMID- 22605543
TI  - Short latency afferent inhibition in Parkinson's disease patients with dementia.
AB  - BACKGROUND: Cortical cholinergic deficiency occurs in Parkinson's disease (PD)
      and is more severe in PD dementia (PDD). Short-latency afferent inhibition (SAI)
      can be used as an in vivo test for the evaluation of the cholinergic circuit in
      the cerebral motor cortex. METHODS: SAI and neuropsychological profile were
      studied in nondemented PD, PDD, Alzheimer's disease (AD) patients, and age
      matched controls. RESULTS: SAI was significantly impaired in AD cases (94.7 +/-
      6.2 versus 55.5 +/- 4.0; P < 0.0001). In PD patients, it was not different from
      controls (61.4 +/- 5.8 versus 55.5 +/- 4.0; P = 0.412). PDD cases demonstrated a
      significant impairment in SAI (91.4 +/- 5.2 versus 55.5 +/- 4.0; P < 0.0001). A
      high correlation was found between SAI and Mini-Mental State Examination (r = 
      0.68; P < 0.0001). CONCLUSIONS: These findings add further evidence that
      differential cholinergic deficiency occurs in PD and PDD. SAI can be a
      neurophysiological correlate of PDD.

PMID- 22605544
TI  - iPhones, iPads, and medical applications for antimicrobial stewardship.
AB  - One of the most important antimicrobial stewardship activities of the infectious
      diseases pharmacist and physician is to provide education and clinical
      information about antimicrobials to health care professionals and patients;
      however, clinician training and continuing education in appropriate antimicrobial
      use in the United States are highly variable and nonstandardized. The iPhone,
      iPad, and the availability of more than 12,000 medical applications (referred to
      as "apps") allow stewardship programs the ability to integrate novel technology
      with point-of-care education. This article reviews medical apps for antimicrobial
      stewardship programs to use on the iPhone or iPad.

PMID- 22605546
TI  - Prognostic value of a hernia sac in congenital diaphragmatic hernia.
AB  - OBJECTIVE: To investigate the prognostic value of a hernia sac in isolated
      congenital diaphragmatic hernia (CDH). METHODS: Our database was searched to
      identify all consecutive cases of CDH referred to our fetal medicine unit between
      January 2004 and August 2011. Presence or absence of a hernia sac was assessed in
      liveborn cases using surgery or postnatal autopsy reports. We studied the
      correlation between the presence of a hernia sac and prenatal findings and
      perinatal morbidity and mortality. RESULTS: Over the study period, there were 70
      cases with isolated CDH born alive in which either a surgery or autopsy report
      was available. Neonatal death, either preoperative or postoperative, occurred in
      1/18 (5.6%) infants with a hernia sac and in 17/52 (32.7%) cases without a hernia
      sac (P = 0.03). Patients with a hernia sac had a significantly higher observed to
      expected pulmonary volume on prenatal magnetic resonance imaging (51.9 vs 39.3%,
      P = 0.01). Neonatal morbidity in surviving infants was lower in the group with a
      hernia sac, although not significantly. CONCLUSION: The presence of a hernia sac
      is associated with a higher pulmonary volume and a better overall prognosis for
      CDH.

PMID- 22605545
TI  - In vitro differentiation of bone marrow derived porcine mesenchymal stem cells to
      endothelial cells.
AB  - Mesenchymal stem cells (MSCs) hold potential for the regeneration of damaged
      tissues in cardiovascular diseases. In this study, we investigated the potential
      of porcine MSCs to differentiate into endothelial cells (ECs) in vitro. The
      cultured bone marrow-derived cells were CD11b-CD34-CD44+CD45-CD90+ and showed
      mesodermal lineage differentiation, which is characteristic of MSCs. The MSCs
      were induced to differentiate into ECs using endothelial growth medium (EGM),
      with and without high concentrations of VEGF (EGM + VEGF; 50 ng/ml). Endothelial
      basal medium (EBM) without growth factors served as the control. The EC
      differentiation was assessed by the presence of vWF, ability to take up
      acetylated LDL, in vitro angiogenesis assay, flow cytometry and qPCR of EC
      markers vWF, VE-cadherin, PECAM-1, VEGF-R1 and VEGF-R2 after 10 days of
      stimulation. Cells cultured in EGM + VEGF medium demonstrated higher amounts of
      DiI-AcLDL-positive cells and enhanced the presence of vWF (90%), VE-Cadherin-
      (60%) and PECAM-1 (48%)-positive cells, than in EBM. These cells showed profuse
      sprouting of capillary tubes and closed polygon formation in the angiogenesis
      assay. There was 1.5-2-fold increase in the mRNA expression of endothelial
      markers in the cells stimulated with EGM + VEGF medium when compared to control.
      The results demonstrate the ability of porcine MSCs to differentiate into ECs
      under in vitro inducing conditions. The differentiated cells would provide new
      options for re-endothelialization following interventional procedures and tissue
      engineering.

PMID- 22605547
TI  - Nano-engineering lattice dimensionality for a soft matter organic functional
      material.
AB  - A high performing electro-optic (EO) chromophore with covalently attached
      coumarin-based pendant groups exhibits intermolecular correlation of coumarin
      units through molecular dynamics (MD) simulations. Unique, orthogonal molecular
      orientations of the chromophore and coumarin units are also evident when
      investigated optically. Such molecular orientation translates to reduced lattice
      dimensionality of the bulk C1 soft matter material system, leading to increased
      acentric order and EO activity. Results are corroborated by nanorheological
      experimental methods.

PMID- 22605548
TI  - The expression of genes involved in glucose metabolism is affected by N-methyl-D
      aspartate receptor antagonism: a putative link between metabolism and an animal
      model of psychosis.
AB  - Psychosis has been associated with glucose metabolism impairment. Here, we
      explored the gene expression of hexokinase 1 (Hk1) and glucose transporter 3
      (GLUT3) after the administration of a subanesthetic or a subconvulsant dose of
      ketamine in rats, considered to provide an animal model of psychosis. Indeed, Hk1
      and GLUT3 are crucially involved in the glucose utilization in brain tissues and
      have also been implicated in the pathophysiology of psychosis. Quantitative brain
      imaging of transcripts was used to evaluate Hk1 and GLUT3 mRNA in rat brain
      regions related to ketamine-induced behavioral abnormalities. Hk1 transcript was
      significantly increased by 50 mg/kg ketamine in cortical and subcortical areas,
      whereas 12 mg/kg ketamine affected Hk1 expression in the auditory cortex only.
      GLUT3 expression was increased by 12 mg/kg ketamine in the frontal cortex and
      decreased by 50 mg/kg ketamine in subcortical areas. The results show that Hk1
      and GLUT3 are extensively and differentially affected by ketamine dose,
      supporting the view that glucose metabolism and psychosis may be causally related
      and suggesting that these molecules may play a role in the pathophysiology of
      ketamine-induced behavioral abnormalities.

PMID- 22605549
TI  - Implications of protein structure instability: from physiological to pathological
      secondary structure.
AB  - Proteins are folded during their synthesis; this process may be spontaneous or
      assisted. Both phenomena are carefully regulated by the "housekeeping" mechanism
      and molecular chaperones to avoid the appearance of misfolded proteins. Unfolding
      process generally occurs during physiological degradation of protein, but in some
      specific cases it results from genetic or environmental changes and does not
      correspond to metabolic needs. The main outcome of these phenomena is the
      appearance of nonfunctional pathologically unfolded proteins with a strong
      tendency to aggregation. Moreover, for some of these unfolded proteins, the
      agglomeration that follows initial proteins association may give rise to highly
      structured soluble aggregates. These aggregates have been identified as the main
      cause of the so-called amyloidosis or amyloid diseases, such as Alzheimer's,
      Parkinson's, and Creutzfeldt-Jakob diseases, and type II diabetes mellitus.
      Although some common mechanisms of amyloid protein aggregation have been
      identified, the roles of the environmental conditions inducing amyloidosis remain
      to be clarified. In this review, we will summarize recent studies identifying the
      origin of amyloid nucleation and will try to predict the therapeutic prospects
      that may be opened by elucidation of the amyloidosis mechanisms.

PMID- 22605550
TI  - Extraction and characterization of a natural rubber from Euphorbia characias
      latex.
AB  - A natural rubber was identified and characterized for the first time in the latex
      of the perennial Mediterranean shrub Euphorbia characias. Four different methods,
      i.e., acetone, acetic acid, trichloroacetic acid, and Triton(r) X-100, followed
      by successive treatments with cyclohexane/ethanol, were employed to extract the
      natural rubber. The rubber content was shown to be 14% (w/v) of the E. characias
      latex, a low content compared with that of Hevea brasiliensis (30-35%) but a
      similar content to other rubber producing plants. E. characias rubber showed a
      molecular weight of 93,000 with a M(w) /M(n) of 2.9. (1) H NMR, (13) C NMR, and
      FTIR analysis revealed the characteristic of the cis-1,4-polyisoprene typical of
      natural rubber. These results provided novel insight into latex components and
      will ultimately benefit the broader understanding of E. characias latex
      composition.

PMID- 22605551
TI  - Polymorphism and higher order structures of protein nanofibers from crude
      mixtures of fish lens crystallins: toward useful materials.
AB  - Protein nanofibers are emerging as useful biological nanomaterials for a number
      of applications, but to realize these applications requires a cheap and readily
      available source of fibril-forming protein material. We have identified fish lens
      crystallins as a feedstock for the production of protein nanofibers and report
      optimized methods for their production. Altering the conditions of formation
      leads to individual protein nanofibers assembling into much larger structures.
      The ability to control the morphology and form higher order structures is a
      crucial step in bottom up assembly of bionanomaterials. Cell toxicity assays
      suggest no adverse impact of these structures on mammalian cell proliferation.
      There are many possible applications for protein nanofibers; here we illustrate
      their potential as templates for nanowire formation, with a simple gold plating
      process.

PMID- 22605552
TI  - Crystal structure of (Gly-Pro-Hyp)(9) : implications for the collagen molecular
      model.
AB  - Collagens have long been believed to adopt a triple-stranded molecular structure
      with a 10/3 symmetry (ten triplet units in three turns) and an axial repeat of 29
      A. This belief even persisted after an alternative structure with a 7/2 symmetry
      (seven triplet units in two turns) with an axial repeat of 20 A had been
      proposed. The uncertainty regarding the helical symmetry of collagens is
      attributed to inadequate X-ray fiber diffraction data. Therefore, for better
      understanding of the collagen helix, single-crystal analyses of peptides with
      simplified characteristic amino acid sequences and similar compositions to
      collagens have long been awaited. Here we report the crystal structure of (Gly
      Pro-Hyp)(9) peptide at a resolution of 1.45 A. The repeating unit of this
      peptide, Gly-Pro-Hyp, is the most typical sequence present in collagens, and it
      has been used as a basic repeating unit in fiber diffraction analyses of
      collagen. The (Gly-Pro-Hyp)(9) peptide adopts a triple-stranded structure with an
      average helical symmetry close to the ideal 7/2 helical model for collagen. This
      observation strongly suggests that the average molecular structure of collagen is
      not the accepted Rich and Crick 10/3 helical model but is a 7/2 helical
      conformation.

PMID- 22605553
TI  - UNAC tetraloops: to what extent do they mimic GNRA tetraloops?
AB  - The structures of four small RNAs each containing a different version of the UNAC
      loop were determined in solution using NMR spectroscopy and restrained molecular
      dynamics. The UMAC tetraloops (where M is A or C) exhibited a typical GNRA fold
      including at least one hydrogen bond between the first U and fourth C. In
      contrast, UGAC and UUAC tetraloops have a different orientation of the first and
      fourth residues, such that they do not closely mimic the GNRA fold. Although the
      UMAC tetraloops are excellent structural mimics of the GNRA tetraloop backbone,
      sequence comparisons typically do not reveal co-variation between the two loop
      types. The limited covariation is attributed to differences in the location of
      potential hydrogen bond donors and acceptors as a result of the replacement of
      the terminal A of GNRA with C in the UMAC version. Thus, UMAC loops do not
      readily form the common GNRA tetraloop-receptor interaction. The loop at
      positions 863-866 in E. coli 16S ribosomal RNA appears to be a major exception.
      However, in this case the GNRA loop does not in fact engage in the usual base to
      backbone tertiary interactions. In summary, UMAC loops are not just an
      alternative sequence version of the GNRA loop family, but instead they expand the
      types of interactions, or lack thereof, that are possible. From a synthetic
      biology perspective their inclusion in an artificial RNA may allow the
      establishment of a stable loop structure while minimizing unwanted long range
      interactions or permitting alternative long-range interactions. (c) 2012 Wiley
      Periodicals, Inc. Biopolymers 97: 617-628, 2012.

PMID- 22605554
TI  - Conformational preferences of 4-chloroproline residues.
AB  - Conformational preferences of the (2S,4R)-4-chloroproline (Clp) and (2S,4S)-4
      chloroproline (clp) residues are explored at the M06-2X/cc-pVTZ//M06-2X/6-31+G(d)
      level of theory in the gas phase and in water, where solvation free energies were
      calculated using the implicit solvation model, and by an X-ray diffraction study
      in the solid state. In the gas phase, the down-puckered gamma-turn structure with
      the trans prolyl peptide bond is most preferred for both Ac-Clp-NHMe and Ac-clp
      NHMe, in which the C(7) hydrogen bond between two terminal groups seems to play a
      role, as found for Ac-Pro-NHMe. In water, the Clp residue has a strong preference
      for the up-puckered PP(II) structure, whereas the up-puckered PP(II) structure
      prevails a little over the down-puckered PP(II) structure for the clp residue,
      similar to the Pro residue. Hence, our calculated results on the puckering
      preference of the Clp and clp residues in water are in accord with the observed
      results deduced from the relative stabilities of the triple helices of the
      collagen model peptides. The X-ray structure of Ac-clp-NHMe was found to be the
      most preferred in water but that of Ac-Clp-NHMe was located as a local minimum
      with DeltaG = 2.0 kcal/mol. In particular, the X-ray structure of Ac-Clp-NHMe was
      quite different from that of Ac-Clp-OMe but similar to that of Ac-Pro-NHMe. The
      lowest rotational barriers to the prolyl cis-trans isomerization for Ac-Clp-NHMe
      become nearly the same as those for Ac-Pro-NHMe in water, whereas the barriers
      are lower by ~2 kcal/mol for Ac-clp-NHMe. It was found that the cis-trans
      isomerization may proceed through the clockwise or anticlockwise rotations for Ac
      Clp-NHMe and the anticlockwise rotation for Ac-clp-NHMe and Ac-Pro-NHMe in water.

PMID- 22605555
TI  - Genotoxicity of poly(propylene imine) dendrimers.
AB  - Dendrimers are highly branched macromolecules with the potential in biomedical
      applications. Due to positively charged surfaces, several dendrimers reveal
      toxicity. Coating peripheral cationic groups with carbohydrate residues can
      reduce it. In this study, the cytotoxicity and genotoxicity of three types of 4th
      generation poly(propylene imine) dendrimers were investigated. Peripheral blood
      mononuclear cells (PBMCs) were treated with uncoated (PPI-g4) dendrimers, and
      dendrimers in which approximately 40% or 90% of peripheral amino groups were
      coated with maltotriose (PPI-g4-OS or PPI-g4-DS) at concentration of 0.05, 0.5, 5
      mg/ml. Abbreviations OS and DS stand for open shell and dense shell respectively,
      that describes the structure of carbohydrate modified dendrimers. After 1 h of
      cell incubation at 37 degrees C, the MTT and comet assays were performed. PPI
      dendrimers demonstrated surface-modification-degree dependent toxicity, although
      genotoxicity of PPI-g4 and PPI-g4-OS measured by the comet assay was
      concentration dependent up to 0.5 mg/ml and at 5 mg/ml the amount of DNA that
      left comet's head decreased. Results may suggest a strong interaction between
      dendrimers and DNA, and furthermore, that coating PPI dendrimers by maltoriose is
      an efficient method to reduce their genotoxicity what opens the possibilities to
      use them as therapeutic agents or drug carriers.

PMID- 22605556
TI  - Reply to "comment on 'binding free energies of inhibitors to iron porphyrin
      complex as a model for cytochrome P450'".

PMID- 22605558
TI  - Differentially degradable janus particles for controlled release applications.
AB  - Janus particles with differentially degradable compartments were prepared by
      electrohydrodynamic (EHD) co-jetting and subsequent controlled crosslinking.
      These bicompartmental particles are composed of an interpenetrating polymer
      network of poly(ethylene oxide) and poly(acrylamide-co-acrylic acid) in one
      hemisphere and a crosslinked copolymer of dextran and poly(acrylamide-co-acrylic
      acid) segments in the second compartment. The compositional anisotropy caused
      differential hydrolytic susceptibility: Although both compartments were stable at
      pH 3.0, selective degradation of the PEO-containing compartment pH 7.4 was
      observed within 5 days. Janus particles with differentially degradable polymer
      compartments may be of interest for a range of oral drug delivery applications
      because of their propensity for decoupled release profiles.

PMID- 22605559
TI  - Cytomorphological and molecular genetic findings in pediatric thyroid fine-needle
      aspiration.
AB  - BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology is largely
      based on data from adult studies. Although thyroid nodules in children are rare,
      the rate of malignancy is high. The authors' aim was to analyze the
      cytomorphology and mutational profiles in pediatric thyroid fine-needle
      aspirations (FNAs). METHODS: Thyroid FNAs from patients 21 years old or younger
      were identified from the authors' pathology archive, categorized using the
      Bethesda System for Reporting Thyroid Cytopathology, and correlated with
      histological and molecular follow-up. RESULTS: A total of 179 samples from 142
      patients were identified, including 96 cases (54%) with histological follow-up
      and 66 cases (37%) with molecular data. The diagnoses included 21 (12%)
      unsatisfactory, 82 (46%) negative, 43 (24%) atypia or follicular lesion of
      undetermined significance, 19 (11%) suspicious for follicular neoplasm, 6 (3%)
      suspicious for malignancy, and 8 (4%) positive for malignancy. The rate of
      malignancy in each category was 0%, 7%, 28%, 58%, 100%, and 100%, respectively.
      Of the 66 FNAs with molecular data, there were 11 (17%) positive for mutations.
      All mutation-positive FNAs were papillary thyroid carcinomas (PTCs) on resection.
      The overall sensitivity and specificity in this population were 80% and 100%,
      respectively. CONCLUSIONS: This study demonstrates that thyroid FNA in children
      is a sensitive and highly specific tool. There was a 17% positivity rate for a
      genetic mutation, which correlated with malignancy in all cases. In comparison to
      adults, there was a higher prevalence of RET/PTC mutations and lower prevalence
      of BRAF mutations, which may in part explain the less aggressive nature of PTCs
      reported in children.

PMID- 22605560
TI  - Diagnosis of levator avulsion injury: a comparison of three methods.
AB  - OBJECTIVE: Levator avulsion is common after vaginal delivery and is strongly
      associated with prolapse and prolapse recurrence. The aim of this study was to
      compare assessment by digital palpation and two ultrasound methods, one using
      rendered volumes and the other multislice imaging, for the diagnosis of levator
      avulsion. METHODS: We retrospectively analyzed randomly identified datasets of
      266 women seen at a tertiary urogynecology unit. Each patient had undergone an
      interview, vaginal examination and 3D/4D translabial ultrasound examination.
      Analysis of the retrieved ultrasound volumes was performed offline, with the
      operator blinded to all clinical data, using two techniques: assessment of
      rendered volumes and evaluation on multislice imaging. We tested agreement
      between the three methods and the association of each method's results with
      symptoms and signs of pelvic organ prolapse. RESULTS: Agreement between the
      findings on palpation and the two ultrasound methods with regard to diagnosis of
      levator avulsion ranged from 80% to 87% (Cohen's kappa, 0.35-0.56). The findings
      for all methods were significantly associated with symptoms, signs and ultrasound
      findings of pelvic organ prolapse (P=0.007 to < 0.001), with no single method
      appearing superior to the others. CONCLUSIONS: Depending on the availability of
      local expertise and equipment, any of the three methods tested in this study may
      be used to document avulsion of the puborectalis muscle.

PMID- 22605561
TI  - Re-ordering chaotic carbon: origins and application of textured carbon.
AB  - Formation of nanocrystals with preferred orientation within the amorphous carbon
      matrix has attracted lots of theoretical and experimental attentions recently.
      Interesting properties of this films, easy fabrication methods and practical
      problems associated with the growth of other carbon nanomaterials such as carbon
      nanotubes (CNTs) and graphene gives this new class of carbon nanostructure a
      potential to be considered as a replacement for some applications such as thermal
      management at nanoscale and interconnects. In this short review paper, the
      fabrication techniques and associated formation mechanisms of these
      nanostructured films have been discussed. Besides, electrical and thermal
      properties of these nanostructured films have been compared with CNTs and
      graphene.

PMID- 22605562
TI  - Radiation-induced early changes in the brain and behavior: serial diffusion
      tensor imaging and behavioral evaluation after graded doses of radiation.
AB  - The nuclear arsenal and the use of nuclear technologies have enhanced the
      likelihood of whole-body/partial-body radiation exposure. The central nervous
      system is highly susceptible to even low doses of radiation. With the aim of
      detecting and monitoring the pathologic changes of radiation-induced damage in
      brain parenchyma, we used serial diffusion tensor magnetic resonance imaging
      (DTI) with a 7T magnetic resonance unit and neurobehavioral assessments mice
      irradiated with 3-, 5-, and 8-Gy doses of radiation. Fractional anisotropy (FA)
      and mean diffusivity (MD) values at each time point (baseline, day 1, day 5, and
      day 10) were quantified from hippocampus, thalamus, hypothalamus, cudate-putamen,
      frontal cortex, sensorimotor cortex, corpus callosum, cingulum, and cerebral
      peduncle. Behavioral tests were performed at baseline, day 5, and day 10. A
      decrease in FA values with time was observed in all three groups. At day 10, dose
      dependent decreases in FA and MD values were observed in all of the regions
      compared with baseline. Behavioral data obtained in this study correlate with FA
      values. Radiation-induced affective disorders were not radiation dose dependent,
      insofar as the anxiety-like symptoms at the lower dose (3 Gy) mimics to the
      symptoms with the higher dose (8 Gy) level but not with the moderate dose.
      However, there was a dose-dependent decline in cognitive function as well as FA
      values. Behavioral data support the DTI indices, so it is suggested that DTI may
      be a useful tool for noninvasive monitoring of radiation-induced brain injury.

PMID- 22605563
TI  - An emulsifier-free RAFT-mediated process for the efficient synthesis of cerium
      oxide/polymer hybrid latexes.
AB  - Hybrid latexes based on cerium oxide nanoparticles are synthesized via an
      emulsifier-free process of emulsion polymerization employing amphiphatic macro
      RAFT agents. Poly(butyl acrylate-co-acrylic acid) random oligomers of various
      compositions and chain lengths are first obtained by RAFT copolymerization in the
      presence of a trithiocarbonate as controlling agent. In a second step, the seeded
      emulsion copolymerization of styrene and methyl acrylate is carried out in the
      presence of nanoceria with macro-RAFT agents adsorbed at their surface, resulting
      in a high incorporation efficiency of cerium oxide nanoparticles in the final
      hybrid latexes, as evidenced by cryo-transmission electron microscopy.

PMID- 22605564
TI  - Cysteine racemization during the Fmoc solid phase peptide synthesis of the Nav1.7
      selective peptide--protoxin II.
AB  - Protoxin II is biologically active peptide containing the inhibitory cystine knot
      motif. A synthetic version of the toxin was generated with standard Fmoc solid
      phase peptide synthesis. If N-methylmorpholine was used as a base during
      synthesis of the linear protoxin II, it was found that a significant amount of
      racemization (approximately 50%) was observed during the process of cysteine
      residue coupling. This racemization could be suppressed by substituting N
      methylmorpholine with 2,4,6-collidine. The crude linear toxin was then air
      oxidized and purified. Electrophysiological assessment of the synthesized
      protoxin II confirmed its previously described interactions with voltage-gated
      sodium channels. Eight other naturally occurring inhibitory knot peptides were
      also synthesized using this same methodology. The inhibitory potencies of these
      synthesized toxins on Nav1.7 and Nav1.2 channels are summarized.

PMID- 22605565
TI  - Ultrasound-guided fine-needle aspiration biopsy of thyroid bed lesions from
      patients with thyroidectomy for thyroid carcinomas.
AB  - BACKGROUND: To evaluate the efficacy and the limitation of fine-needle aspiration
      (FNA) biopsy in thyroid bed lesions, a retrospective review was performed of the
      medical records of thyroid cancer patients who underwent ultrasound-guided FNA
      biopsy of the thyroid bed at The University of Texas MD Anderson Cancer Center
      over a 5-year period. METHODS: Data were reviewed on 220 FNA biopsies taken from
      thyroid bed lesions in 195 patients who had undergone thyroidectomy for thyroid
      carcinoma. Thyroid bed FNA results were compared with clinical follow-up,
      including neck dissection results. RESULTS: Recurrent carcinoma was diagnosed by
      FNA biopsy in 139 of 220 (63%) cases. Neck dissections were performed for 112
      sites identified by FNA biopsies, and recurrent carcinoma was confirmed in 110
      sites. The concordance between positive and/or suspicious FNA diagnosis and
      positive neck dissection results was 98% (118 of 120 cases). A false-positive FNA
      occurred in one patient with follicular thyroid carcinoma. The other discrepancy
      was attributed to failure to remove the lesion by neck dissection. The diagnostic
      accuracy of thyroid bed FNA was 100% in papillary and medullary thyroid carcinoma
      and 93% in follicular thyroid carcinoma. Suspicious and rare false-negative FNA
      results were attributed to low cellularity and lack of characteristic
      cytomorphologic features of thyroid carcinoma. CONCLUSIONS: Ultrasound-guided
      thyroid bed FNA biopsy is accurate and efficient in triaging patients who require
      post-thyroidectomy follow-up for recurrent thyroid carcinoma. Caution should be
      taken in the interpretation of FNA specimens that have low cellularity and lack
      characteristic cytologic features of thyroid carcinoma.

PMID- 22605566
TI  - Postmortem examination of human fetal hearts at or below 20 weeks' gestation: a
      comparison of high-field MRI at 9.4 T with lower-field MRI magnets and
      stereomicroscopic autopsy.
AB  - OBJECTIVES: To compare the diagnostic usefulness of high-field with low-field
      magnetic resonance imaging (MRI) and stereomicroscopic autopsy for examination of
      the heart in fetuses at or under 20 weeks' gestation. METHODS: Prior to invasive
      stereomicroscopic autopsy, MRI scans at 9.4, 3.0 and 1.5 T were performed on 24
      fetuses between 11 and 20 weeks' gestation, including 10 fetuses with cardiac
      abnormalities. The ability to visualize different heart structures was evaluated
      according to the different field strength MRI magnets used and gestational age at
      examination. RESULTS: On 1.5- and 3.0-T MRI, only the heart situs and four
      chamber view could be visualized consistently (in 75% or more of cases) when the
      fetus was beyond 16 weeks' gestation, but other heart structures could not be
      visualized for fetuses at any gestational age. In contrast, using high-field MRI
      at 9.4 T, the heart situs, four-chamber view and the outflow tracts could be
      visualized in all fetuses irrespective of gestational age. Using high-field MRI,
      the sensitivity for detecting an abnormality of the four-chamber view was 66.7%
      (95% CI, 30.1-92.1%) with a specificity of 80.0% (95% CI, 51.9-95.4%). For
      abnormalities of the outflow tracts, sensitivity was 75.0% (95% CI, 20.3-95.9%)
      and specificity 100.0% (95% CI, 83.3-100.0%). Eight fetuses out of 10 with
      congenital heart disease (CHD) were classified as having major CHD. High-field
      MRI at 9.4 T was able to identify seven out of the eight cases of major CHD.
      CONCLUSION: High-field MRI at 9.4 T seems to be an acceptable alternative
      approach to invasive stereomicroscopic autopsy for fetuses with CHD at or below
      20 weeks' gestation.

PMID- 22605567
TI  - Graphene oxide as a novel nanoplatform for enhancement of aggregation-induced
      emission of silole fluorophores.

PMID- 22605568
TI  - Zinc undecylenate catalyst for the ring-opening polymerization of caprolactone
      monomers.
AB  - The ring-opening polymerization of two caprolactone monomers catalyzed by zinc
      undecylenate (ZU) is reported. Polymerizations were performed in bulk with benzyl
      alcohol (BnOH) as an initiator at 90 and 110  degrees C, respectively. A slower
      polymerization rate was observed for gamma-octyloxy-epsilon-caprolactone as
      compared to epsilon-caprolactone. Diblock copolymers were synthesized by the
      sequential monomer addition at 90 and 110  degrees C. The kinetic studies
      performed for the ring-opening polymerization of epsilon-caprolactone and gamma
      octyloxy-epsilon-caprolactone and the successful synthesis of diblock copolymers
      by the sequential monomer addition confirmed the controlled/living nature of zinc
      undecylenate catalyzed reactions.

PMID- 22605569
TI  - Biochemical and morphological characterization of MAGI-1 in neuronal tissue.
AB  - The membrane-associated guanylate kinase with inverted organization (MAGI)
      proteins consist of three members, MAGI-1, MAGI-2 (also known as S-SCAM), and
      MAGI-3. Although MAGI-2 has been analyzed and shown to interact with a variety of
      postsynaptic proteins, functional analyses and characterization of MAGI-1 in
      neuronal tissues have been rare. In this study, we prepared a specific antibody
      against MAGI-1, anti-MAGI-1, and carried out biochemical and morphological
      analyses of MAGI-1 in rat neuronal tissues. By Western blotting, a high level of
      MAGI-1 was detected in nervous tissues, especially in olfactory bulb. Biochemical
      fractionation clarified that MAGI-1 was relatively enriched in the synaptosomal
      vesicle and synaptic plasma membrane fractions, whereas MAGI-2 and MAGI-3
      appeared to be in the synaptic plasma membrane and postsynaptic density
      fractions. Immunofluorescent analyses revealed diffuse distribution of MAGI-1 in
      the cell body and processes of primary cultured rat hippocampal neurons, whereas
      MAGI-2 and MAGI-3 were likely to be enriched at synapses. Immunohistochemical
      analyses demonstrated that MAGI-1 was expressed in Purkinje cells, in hypocampal
      neurons in CA1 region, in the glomerulus region of olfactory bulb, and at the
      dorsal root entry zone in embryonic rat spinal cord. These results suggest
      neuronal roles of MAGI-1 different from those of MAGI-2/3.

PMID- 22605570
TI  - Randomized, double-blind, placebo-controlled trial of sulindac in individuals at
      risk for melanoma: evaluation of potential chemopreventive activity.
AB  - BACKGROUND: Reduced melanoma risk has been reported with regular use of
      nonsteroidal anti-inflammatory drugs (NSAIDs). However, the ability of NSAIDs to
      reach melanocytes in vivo and modulate key biomarkers in preneoplastic lesions
      such as atypical nevi has not been evaluated. METHODS: This randomized, double
      blind, placebo-controlled trial of sulindac was conducted in individuals with
      atypical nevi (AN) to determine bioavailability of sulindac and metabolites in
      nevi and effect on apoptosis and vascular endothelial growth factor A (VEGFA)
      expression in AN. Fifty subjects with AN >= 4 mm in size and 1 benign nevus (BN)
      were randomized to sulindac (150 mg twice a day) or placebo for 8 weeks. Two AN
      were randomized for baseline excision, and 2 AN and BN were excised after
      intervention. RESULTS: Postintervention sulindac, sulindac sulfone, and sulindac
      sulfide concentrations were 0.31 +/- 0.36, 1.56 +/- 1.35, and 2.25 +/- 2.24
      MUg/mL in plasma, and 0.51 +/- 1.05, 1.38 +/- 2.86, and 0.12 +/- 0.12 MUg/g in
      BN, respectively. Sulindac intervention did not significantly change VEGFA
      expression but did increase expression of the apoptotic marker cleaved caspase-3
      in AN (increase of 3 +/- 33 in sulindac vs decrease of 25 +/- 45 in the placebo
      arm, P = .0056), although significance was attenuated (P = .1103) after adjusting
      for baseline expression. CONCLUSIONS: Eight weeks of sulindac intervention
      resulted in high concentrations of sulindac sulfone, a proapoptotic metabolite,
      in BN but did not effectively modulate VEGFA and cleaved caspase-3 expression.
      Study limitations included limited exposure time to sulindac and the need to
      optimize a panel of biomarkers for NSAID intervention studies.

PMID- 22605571
TI  - Cytopathologic evaluation of the in situ margin in patients undergoing
      hepatectomy.
AB  - BACKGROUND: Margin status is a predictor of outcome for patients with liver
      malignancies, although what constitutes a negative margin is controversial.
      Traditionally, the completeness of resection is estimated by surgical
      histopathology of the resected specimen margin, despite the in situ margin being
      potentially more important. The true margin is often altered by parenchymal
      transection techniques. The authors propose that cytologic assessment of the in
      situ margin is more specific for determining the true margin. METHODS: A total of
      84 patients with primary or metastatic liver tumors who were undergoing surgical
      resection were enrolled in this prospective Institutional Review Board-approved
      study. Specimen and in situ (patient) margins were assessed using a "scrape
      preparation" cytologic technique and compared with traditional surgical
      histopathology. Patients were followed for assessment of local disease
      recurrence. RESULTS: Follow-up data were complete for 64 patients for a median of
      37 months (range, 12 months-56 months). Twenty patients were excluded because of
      perioperative death (6 patients; 7%) or a follow-up of < 12 months. Seven
      patients (12.2%) had positive histopathologic specimen margins, but only 1 was
      found to be positive by cytology (1.8%). No in situ cytologically positive
      margins were identified along the cut edge of the liver remnant. The rate of
      intra- or extrahepatic recurrences was 56.7%, whereas the local recurrence rate
      was 1.8%. One patient with local recurrence demonstrated simultaneous intra- and
      extrahepatic disease recurrences and had negative margins by all methods of
      evaluation. CONCLUSIONS: To the authors' knowledge, the current study is the
      first to demonstrate that in situ margins can be assessed using cytopathology.
      This method is quick and can be universally applied. Given the difficulty of
      accurately assessing margins after hepatectomy, cytopathologic evaluation may be
      more reflective of the true margin. Cancer (Cancer Cytopathol) 2012. (c) 2012
      American Cancer Society.

PMID- 22605575
TI  - Molecular nanoworm with PCL core and PEO shell as a non-spherical carrier for
      drug delivery.
AB  - Core/shell wormlike polymer brushes with densely grafted poly(epsilon
      caprolactone)-b-poly(ethylene oxide) (PCL-b-PEO) are synthesized via grafting an
      alkynyl terminated PCL-b-PEO (ay-PCL(17) -b-PEO(113) ) onto a well-defined azido
      functionalized polymethacrylate (PGA(940) ) and are evaluated preliminarily as a
      single molecular cylindrical vehicle for drug delivery. Water soluble molecular
      worms of ca. 230 nm are obtained and then the anticancer drug doxorubicin (DOX)
      is loaded into its PCL core by hydrophobic interaction. Compared with spherical
      micelles from linear PCL(17) -b-PEO(113) , the brushes demonstrate a lower
      loading efficiency but a faster release rate of DOX. Confocal laser scanning
      microscopy measurements show that DOX-loaded cylindrical molecular brushes can
      easily enter into HeLa and HepG2 cells in 1 h.

PMID- 22605574
TI  - Learning process for performing and analyzing 3D/4D transperineal ultrasound
      imaging and interobserver reliability study.
AB  - OBJECTIVES: To evaluate the learning process for acquiring three- and four
      dimensional (3D/4D) transperineal ultrasound volumes of the levator hiatus (LH)
      dimensions at rest, during pelvic floor muscle (PFM) contraction and on Valsalva
      maneuver, and for analyzing the ultrasound volumes, as well as to perform an
      interobserver reliability study between two independent ultrasound examiners.
      METHODS: This was a prospective study including 22 women. We monitored the
      learning process of an inexperienced examiner (IE) performing 3D/4D transperineal
      ultrasonography and analyzing the volumes. The examination included acquiring
      volumes during three PFM contractions and three Valsalva maneuvers. LH dimensions
      were determined in the axial plane. The learning process was documented by
      estimating agreement between the IE and an experienced examiner (E) using the
      intraclass correlation coefficient. Agreement was calculated in blocks of 10
      ultrasound examinations and analyzed volumes. After the learning process was
      complete the interobserver reliability for the technique was calculated between
      these two independent examiners. RESULTS: For offline analysis of the first 10
      ultrasound volumes obtained by E, good to very good agreement between E and IE
      was achieved for all LH measurements except for the left and right levator
      urethra gap and pubic arc. For the next 10 analyzed volumes, agreement improved
      for all LH measurements. Volumes that had been obtained by IE and E were then re
      evaluated by IE, and good to very good agreement was found for all LH
      measurements indicating consistency in volume acquisition. The interobserver
      reliability study showed excellent ICC values (ICC, 0.81-0.97) for all LH
      measurements except the pubic arc (ICC = 0.67). CONCLUSION: 3D/4D transperineal
      ultrasound is a reliable technique that can be learned in a short period of time.

PMID- 22605573
TI  - Dietary fat types and 4-year cognitive change in community-dwelling older women.
AB  - OBJECTIVE: A study was undertaken to relate dietary fat types to cognitive change
      in healthy community-based elders. METHODS: Among 6,183 older participants in the
      Women's Health Study, we related intake of major fatty acids (saturated [SFA],
      monounsaturated [MUFA], total polyunsaturated [PUFA], trans-unsaturated) to late
      life cognitive trajectory. Serial cognitive testing, conducted over 4 years,
      began 5 years after dietary assessment. Primary outcomes were global cognition
      (averaging tests of general cognition, verbal memory, and semantic fluency) and
      verbal memory (averaging tests of recall). We used analyses of response profiles
      and logistic regression to estimate multivariate-adjusted differences in
      cognitive trajectory and risk of worst cognitive change (worst 10%) by fat
      intake. RESULTS: Higher SFA intake was associated with worse global cognitive (p
      for linear trend = 0.008) and verbal memory (p for linear trend = 0.01)
      trajectories. There was a higher risk of worst cognitive change, comparing
      highest versus lowest SFA quintiles; the multivariate-adjusted odds ratio (OR)
      with 95% confidence interval (CI) was 1.64 (1.04-2.58) for global cognition and
      1.65 (1.04-2.61) for verbal memory. By contrast, higher MUFA intake was related
      to better global cognitive (p for linear trend < 0.001) and verbal memory (p for
      linear trend = 0.009) trajectories, and lower OR (95% CI) of worst cognitive
      change in global cognition (0.52 [0.31-0.88]) and verbal memory (0.56 [0.34
      0.94]). Total fat, PUFA, and trans-fat intakes were not associated with cognitive
      trajectory. INTERPRETATION: Higher SFA intake was associated with worse global
      cognitive and verbal memory trajectories, whereas higher MUFA intake was related
      to better trajectories. Thus, different consumption levels of the major specific
      fat types, rather than total fat intake itself, appeared to influence cognitive
      aging.

PMID- 22605576
TI  - Impact of numerical variation in FMS-like tyrosine kinase receptor 3 internal
      tandem duplications on clinical outcome in normal karyotype acute myelogenous
      leukemia.
AB  - BACKGROUND: The impact of single versus multiple fms-like tyrosine kinase
      receptor 3 internal tandem duplication (FLT3-ITD) mutations on the clinical
      outcome of patients with acute myelogenous leukemia has not been well studied,
      and particularly has not been investigated while simultaneously accounting for
      the quantitative mutation burden. METHODS: The authors conducted a multivariate
      analysis of overall survival, event-free survival, and complete remission
      duration, including numeric variation (single vs multiple) and quantitative
      mutant burden of FLT3-ITD as variables among other clinically relevant factors.
      RESULTS: An analysis of a cohort of 1043 patients with AML demonstrated that,
      among patients with normal-karyotype acute myelogenous leukemia and FLT3-ITD
      mutation, overall survival and event-free survival were not affected by the
      number of FLT3-ITD mutations, but complete remission duration was significantly
      longer in patients who had multiple FLT3-ITD mutations (median, 86 weeks vs 34
      weeks; P = .03). CONCLUSIONS: The current results indicated that time-to-event
      analyses of patients with normal-karyotype acute myelogenous leukemia and FLT3
      ITD mutation should take into account the number of mutations and the mutant
      burden, among other factors.

PMID- 22605577
TI  - A global public health strategy for autism spectrum disorders.
AB  - In recent years, there has been increasing awareness about autism spectrum
      disorders (ASD) around the world, including in low and middle income countries.
      Unlike countries in Western Europe and North America where infrastructure and
      capacity are available to help meet some of the needs of individuals with ASD,
      little expertise or capacity exists in most of the developing world. In 2008
      Autism Speaks launched the Global Autism Public Health (GAPH) Initiative to
      facilitate the development of systematic and sustainable solutions for enhancing
      global autism awareness, research, training and service delivery. In the last 3
      years Autism Speaks has established collaboration with stakeholders from over 20
      countries who are working alongside dedicated local and international
      stakeholders to effect change. In this article, the GAPH framework is described,
      along with a few brief case examples that illustrate how the framework for
      implementation of the model can occur. GAPH is still in its infancy but has the
      potential to have significant impact through inclusive collaboration with local
      and international stakeholders to develop effective and sustainable public health
      solutions for disseminating best practices and delivering tangible benefits to
      individuals with ASD and their families.

PMID- 22605578
TI  - Low threshold, amplified spontaneous emission from core-seeded semiconductor
      nanotetrapods incorporated into a sol-gel matrix.

PMID- 22605579
TI  - Doublecortin and doublecortin-like are expressed in overlapping and non
      overlapping neuronal cell population: implications for neurogenesis.
AB  - We have characterized the expression of doublecortin-like (DCL), a microtubule
      associated protein involved in embryonic neurogenesis that is highly homologous
      to doublecortin (DCX), in the adult mouse brain. To this end, we developed a DCL
      specific antibody and used this to compare DCL expression with DCX. In the
      neurogenic regions of the adult brain like the subventricular zone (SVZ), the
      rostral migratory stream (RMS), the olfactory bulb (OB), and the hippocampus, DCL
      colocalizes with DCX in immature neuronal cell populations. In contrast to DCX,
      we also found high DCL expression in three other brain regions with suspected
      neurogenesis or neuronal plasticity. First, the radial glia-like, hypothalamic
      tanycytes show high DCL expression that partly colocalizes with the neural stem
      cell marker vimentin. Second, DCL expression is found in cells of the
      suprachiasmatic nucleus (SCN), which lacks expression of the adult neuron marker
      NeuN. Third, a novel region exhibiting DCL expression is part of the olfactory
      tubercle where DCL is found in the neuropil of the islands of Calleja (ICj). Our
      findings define DCL as a novel marker for specific aspects of adult neurogenesis,
      which partly overlap with DCX. In addition, we propose unique roles for DCL in
      adult neurogenesis and we suggest high levels of neuronal plasticity in
      tanycytes, SCN, and ICj.

PMID- 22605580
TI  - Risk in complex genetics: "all models are wrong but some are useful".
AB  - Although genome-wide association studies (GWAS) have proven remarkably effective
      at identifying reliably associated genetic variants, the biology underlying these
      discoveries is rarely immediately apparent and in most cases seems bound to
      require extensive fine mapping and functional analysis before it is revealed. In
      this context, it is logical and appropriate to try to interrogate available
      genetic data for biological insights. However, because such efforts invariably
      depend upon mathematical modeling, misperceptions can easily arise if the
      relevant mathematical properties are overlooked or forgotten. In this report, we
      will examine these mathematical issues, highlight some of the more common
      misconceptions, and hopefully help to clarify the somewhat blurry distinction
      between biology and mathematics that can so easily undermine and obscure the
      value of GWAS discoveries.

PMID- 22605581
TI  - It is never too late: ultra-late recurrence of melanoma with distant metastases.
AB  - The authors present the case of a 73-year-old lady presenting with weight loss,
      personality changes, transient confusion and visual loss, 38 years after initial
      surgical excision of a melanoma of the neck. CT and MRI of the brain showed
      cerebral metastases and positron emission tomography (PET)-CT showed an
      additional fludeoxyglucose avid lesion in the lung, which was biopsied. Histology
      confirmed metastatic malignant melanoma. She declined whole brain radiotherapy in
      favour of best supportive care and died 4 months after diagnosis. Life-long
      vigilance among patients with previous melanoma and awareness among physicians
      are necessary if late recurrences are to be recognised early, and outcomes
      improved. New imaging techniques including PET-CT may be helpful in diagnosing
      and staging melanoma recurrence. Treatment options for patients presenting with
      distant metastases are limited and the prognosis remains poor.

PMID- 22605582
TI  - Is it dextrocardia or dextroversion?

PMID- 22605583
TI  - Tumefactive demyelination-to cracks the nut without cracking the pot.
AB  - A 45-year-old female recently detected diabetic, admitted with difficulty in
      walking, irrelevant talk and urinary incontinence for 3 weeks and deviation of
      angle of mouth to left. Examination revealed pallor, delusional thoughts, right
      upper motor neuron facial weakness, ataxia. CT brain revealed bulky hyperdense
      lesion in corpus callosum and subsequently MRI of the brain revealed T2
      hyperintense lesions involving genu and body of corpus callosum with restricted
      diffusion, and MR spectroscopy revealed reduced uptake of choline. Possibilities
      considered were infiltrative glioma of corpus callosum, demyelination and central
      nervous system lymphoma. As the patient and relatives were not willing to allow
      stereotactic biopsy, she was started on steroids. Her neurological deficits
      started improving and 1 month later repeat MRI brain showed a drastic reduction
      in the size of the lesion. Her neurological condition disappeared and is doing
      well.

PMID- 22605584
TI  - Stomach in a parastomal hernia: uncommon presentation.
AB  - Parastomal herniae are among the most common complications of stoma formation.
      The authors present an unusual case of a 41-year-old lady who presented with
      frequent early postprandial vomiting devoid of bile, upper abdominal distension
      and weight loss in the preceding 4 weeks losing weight for the last 4 weeks.
      Barium meal revealed herniation of the stomach through the gastric wall causing
      gastric outlet obstruction. Intraoperatively she was found to have a subcutaneous
      incarcerated parastomal hernia containing viable stomach and small bowel loops.
      The hernial contents were reduced back into the peritoneum and the abdominal wall
      defect repaired using the open sombrero repair technique.

PMID- 22605585
TI  - Unusual retention of two flatus tubes inserted for sigmoid volvulus.

PMID- 22605586
TI  - Myocardial infarction due to coronary steal caused by a congenital unilateral
      absence of the right pulmonary artery: a rare case.
AB  - A 27-year-old male patient presented with symptoms that mimic an acute coronary
      syndrome and associated with significant myocardial perfusion ischaemic defects.
      The latter was detected by adenosine stress Tc-99m estamibi single photon
      emission CT. However, subsequently the CT angiogram revealed a normal coronary
      arteries outline and calibre with prominent coronary artery collaterals filling
      the distal branches of the absent right pulmonary artery.

PMID- 22605587
TI  - Kleine Levin syndrome in Malaysia: first typical case.
AB  - A 13-year-old boy presented with a 2 weeks history of tearfulness, childish
      behaviour, separation anxiety, hypersomnia, hyperphagia and sexual disinhibition
      following a brief episode of fever. He had been experiencing the episodes since
      he was seven. The episodes lasted from a few days to 3 weeks and would normally
      occur once in a year. Most of the time it started with fever and resolved
      spontaneously. In the past he described auditory hallucination but not this time.
      Examination revealed a slightly overweight adolescent male appearing appropriate
      to his age. During the session he was restless, sleepy and burst into tears
      frequently. He constantly asked his mother when he could go home to sleep. He was
      very childish and clung to his mother. He was given a trial of risperidone 1 mg
      to be taken once a day for 3 days. On follow-up he had completely recovered.

PMID- 22605588
TI  - Fish bone migration: an unusual cause of liver abscess.
AB  - Treating a pyogenic liver abscess is a therapeutic challenge when a patient
      presents with atypical symptoms. One of the rare causes of treatment failure of
      these abscesses is the unrecognised migration of a foreign body from the
      gastrointestinal tract. The authors describe a pyogenic liver abscess in a 45
      year-old male who presented with a 10 day history of fever, and abdominal pain. A
      CT scan of the abdomen revealed a needle-like foreign body in the liver. At
      operation a 2.5 cm fish bone was extracted from the liver. Subsequently, his
      feverish symptoms disappeared, and he has remained well in the ensuing 3 month
      postoperative period. Fish bone-induced liver abscess is discussed in this brief
      report.

PMID- 22605589
TI  - Fatal cumulative toxicities of HAART in a stable, AIDS-free, HIV-infected
      patient.
AB  - The authors describe the case of fatal cumulative toxicities in a 58-year-old
      AIDS-free, HIV-infected patient, who successively developed under highly active
      antiretroviral therapy (HAART): severe lipodystrophy, complicated osteoporosis,
      complicated non-cirrhotic portal hypertension of the liver (with ascites, portal
      thrombosis, oesophageal varices and protein-losing enteropathy) due to nodular
      regenerative hyperplasia. These cumulative HAART-related toxicities led to death,
      despite symptomatic treatment and the switch of antiretrovirals (especially
      didanosine) putatively involved in the process in these drug-mediated diseases.
      As morbidity and mortality in HIV infection continue to improve, it appears
      important to recognise such rare HAART-associated toxicities. This case
      illustrates the absolute necessity of investigating the long-term side effects of
      HAART in HIV infection, particularly in patients treated with first generation
      molecules. The switch strategy (switching old molecules to newer ones) is crucial
      in case of severe suspected toxicity and has to be discussed in asymptomatic
      patients largely exposed to first generation molecules, in order to prevent long
      term toxicity.

PMID- 22605590
TI  - A simple football injury leading to a grade 4 renal trauma.
AB  - This case highlights the need for cautious management and serial regular
      examination of trauma patients. A 22-year-old Caucasian male presented to the
      emergency department 4 h following an injury sustained during football training.
      He complained of the immediate onset of severe left upper quadrant and left flank
      pain. He subsequently developed frank haematuria. On initial review, he was
      haemodynamically stable. CT of the abdomen and pelvis showed a grade 4 renal
      trauma. Over the following 36 h, he remained haemodynamically stable. On serial
      abdominal examinations however, he developed a rigid abdomen and was noted to
      have a haemoglobin drop. Interval CT scan showed a progression of his injury and
      the presence of a haemoperitoneum. An emergency laparotomy was performed
      resulting in a left nephrectomy. He made an uneventful recovery.

PMID- 22605591
TI  - Antiphospholipid syndrome and recurrent thrombosis--limitations of current
      treatment strategies.
AB  - Antiphospholipid syndrome (APS) is a systemic autoimmune disorder that is
      characterised by the presence of antiphospholipid antibodies and a common cause
      of vascular thromboembolic phenomena. The management of patients with APS is
      currently directed to antithrombotic medications. The international therapeutic
      guidelines recommend oral anticoagulation with warfarin indefinitely after the
      first thrombotic episode. However, therapeutic guidelines lack for a minority
      group of patients - the patients appropriately anticoagulated with recurrent
      thromboembolic phenomena. The authors present a clinical report that reveals the
      therapeutic and diagnostic complexity of this specific group of patients.
      Regarding recent studies, APS has been revealed as a complex syndrome with
      multiple pathophysiological mechanisms previously unknown. In this context, new
      therapeutic approaches have been defended and empirically experienced, with
      potentially promising results.

PMID- 22605592
TI  - Multiple arthritis: three in one.

PMID- 22605593
TI  - Haloperidol induced obsessive compulsive symptom (OCS) in a patient with learning
      disability and bipolar affective disorder.
AB  - In this case report, a patient with severe learning disability and bipolar
      affective disorder developed de-nova obsessive compulsive symptom (OCS) with
      haloperidol, a conventional antipsychotic medication and the OCS stopped with
      stopping haloperidol. Antipsychotics are recommended and used as augmentation
      therapy in resistant cases of obsessive compulsive disorder. Although second
      generation antipsychotics have been reported to have induced OCS but haloperidol,
      which is a first generation antipsychotic has not been implicated in OCS
      induction. There is no published report of antipsychotics induced OCS in learning
      disability population. Clinician should be aware of this potential side effect of
      haloperidol.

PMID- 22605594
TI  - Thoracic inlet syndrome--a diagnosis made on CT pulmonary angiogram.

PMID- 22605595
TI  - An interesting case of intramyometrial pregnancy.
AB  - A 27-year-old woman, gravida 3, para 1, at 9 weeks gestation, initially presented
      with clinical and ultrasonographic features suggestive of a missed spontaneous
      abortion for which surgical evacuation was performed. A diagnosis of ectopic
      pregnancy was made as on histological review no fetal or chorionic tissue was
      seen. Medical management for an ectopic pregnancy was initiated. Following
      methotrexate administration she was readmitted with severe abdominal pain.
      Findings on diagnostic laparoscopy revealed an asymmetrically enlarged swollen
      fundus. Hysteroscopy was performed concurrently demonstrating an empty uterine
      cavity. A diagnosis of intramyometrial pregnancy was made based on these
      findings. An MRI scan was performed postprocedure which supported the diagnosis.
      In view of her parity and future fertility medical management was adopted with
      methotrexate. She was followed up until hormone levels returned to baseline and
      serial scans showed a healed solid collection.

PMID- 22605596
TI  - Multiple brain lesions in a young man with hypernatraemia.

PMID- 22605597
TI  - Pemphigus vulgaris--a report of three cases.
AB  - Pemphigus vulgaris (PV) is a potentially life-threatening illness that manifests
      in the mouth and on skin. In a majority of patients it affects the oral mucosa
      and is sometimes difficult to diagnose when only mucosal involvement is present.
      In an attempt to highlight the proper treatment plan of this potentially fatal
      disorder, the authors document a report of three cases. These patients were
      prescribed conventional steroids which brought about partial relief but early
      recurrence with discontinuation of the drug. Subsequent management of these
      patients with azathioprine along with corticosteroids improved the outcome of the
      disease with longer remission periods. In this case series, the steroid sparing
      effect of azathioprine was achieved successfully and hence needs to be considered
      as a primary drug in management of PV.

PMID- 22605598
TI  - Neurosurgical management of L-asparaginase induced haemorrhagic stroke.
AB  - The authors describe a case of L-asparaginase induced intracranial thrombosis and
      subsequent haemorrhage in a newly diagnosed 30-year-old man with acute
      lymphoblastic leukaemia who was successfully managed by surgical intervention. At
      presentation, he had a Glasgow Coma Score of 7/15, was aphasic and had dense
      right hemiplegia. Neuroimaging revealed an acute anterior left middle cerebral
      artery infarct with parenchymal haemorrhagic conversion, mass effect and
      subfalcine herniation. He subsequently underwent left frontal craniotomy and
      evacuation of large frontal haematoma and decompressive craniectomy for cerebral
      oedema. Six months postoperatively he underwent titanium cranioplasty. He had
      made good clinical recovery and is currently mobilising independently with mild
      occasional episodes of expressive dysphasia, difficulty with fine motor movement
      on the right side, and has remained seizure free. This is the first documented
      case of L-asparaginase induced haemorrhagic stroke managed by neurosurgical
      intervention. The authors emphasise the possible role of surgery in managing
      chemotherapy induced intracranial complications.

PMID- 22605599
TI  - Urinary tuberculosis associated to adalimumab.

PMID- 22605600
TI  - Proliferative retinopathy in Cowden syndrome.
AB  - Cowden syndrome is a multiple hamartoma syndrome with a high risk of breast and
      thyroid tumours, both benign and malignant. The authors report a 24-year-old
      female patient who presented with reduced vision in both eyes. Ocular examination
      showed vitreous haemorrhage secondary to retinal new vessels in both eyes. There
      was no evidence of diabetes mellitus, and she had a wide range of normal
      investigations. She was labelled as idiopathic retinal neovascularisation.
      Fifteen years later, she presented with a lump in her left breast and a previous
      history of excision of a benign lump from her right breast. She also reported
      multiple tumours in her family. Clinical diagnosis of Cowden syndrome was made
      and genetic testing confirmed mutation of the PTEN gene.

PMID- 22605601
TI  - Pleomorphic high-grade sarcoma of the heart mimicking cardiac myxoma.

PMID- 22605602
TI  - Progressive, massive osteolysis of mandible (Gorham's disease): report of a case.
AB  - A rare case of progressive osteolysis of mandible is discussed with
      clinicoradiological presentation. The purpose of the case report is to make the
      medical community aware of this rare and fascinating disorder in the
      maxillofacial region. The disease is characterised by spontaneous progressive
      osteolysis of one or more skeletal bones. Occurrence in maxillofacial region is
      rare with fewer than 35 reported cases affecting the facial and jaw bones. The
      present case report is about the mystery of bilaterally missing ascending rami.
      An attempt is made to draw attention of the medical fraternity to this unusual
      and rare entity which can induce instability, dysfunction and cosmetic
      disturbances.

PMID- 22605603
TI  - Xanthogranulomatous pyelonephritis in early infancy.
AB  - Xanthogranulomatous pyelonephritis is a severe, atypical form of chronic renal
      parenchymal infection, which mimics neoplasia and other inflammatory renal
      parenchymal diseases. Although xanthogranulomatous pyelonephritis has
      characteristic findings on sonography and CT scan, a clinical diagnosis is seldom
      possible. Correct diagnosis is made on exploration, by the presence of dense
      adhesions to the surrounding tissue and presence of pus in the kidney, which is
      confirmed histopathologically by the presence of lipid laden foamy macrophages,
      accompanied by both chronic and acute phase inflammatory cells.

PMID- 22605604
TI  - 'Fungal spondylodiscitis in a non-immunocompromised patient'.
AB  - Spondylodiscitis is an inflammatory disease, usually infectious, of one or more
      vertebral bodies and of corresponding intervertebral discs. The fungal aetiology
      is rare (less than 5% of cases), affecting mostly immunocompromised individuals.
      It is often a delayed diagnosis by the indolence of symptoms, presenting itself
      as a serious infection, which may result in important functional consequences.
      The authors present the case of a 75-year-old male, with constitutional
      complaints and intense back pain. Prior recent history of left hemicolectomy due
      to diverticulitis with multiple surgical complications, resulted in prolonged
      intensive care unit hospitalisation, and, later on, an episode of fungal
      endophthalmitis. The diagnosis of spondylodiscitis L5/S1 was performed by MRI.
      The patient underwent surgical disco-vertebral debridement and isolation of a
      Candida albicans was seen in the collected surgical material. No evidence of an
      immunossupressive status was found. Treatment was complemented with liposomal
      amphotericin B in the maximum recommended dose.

PMID- 22605605
TI  - Unusual cause of cholangitis and diarrhoea after cholecystectomy.

PMID- 22605606
TI  - Chronic diarrhoea from mycophenolate mofetil-induced colitis.

PMID- 22605607
TI  - Allergic bronchopulmonary aspergillosis causing total lung collapse.
AB  - Allergic bronchopulmonary aspergillosis (ABPA) is commonly associated with
      underlying respiratory disease. The authors present the case of a 68-year-old non
      smoker, admitted with a possible acute coronary syndrome, who deteriorated in
      hospital secondary to total left lung collapse as demonstrated on chest
      radiograph. There was no significant history of respiratory disease. Histology
      from bronchoscopy and lavage indicated lung carcinoma; however biopsy and CT
      staging demonstrated APBA. This is the first report of lung collapse secondary to
      ABPA in which initial bronchoscopy suggested underlying carcinoma.

PMID- 22605608
TI  - A severe case of iatrogenic lactation ketoacidosis.
AB  - Lactation ketosis is a recognised disorder in postpartum lactating cows where a
      negative energy balance develops because the energy demands of milk production
      exceed the energy capacity of the animal. Rarely, nursing women can develop
      problems with lactation ketosis when their glycogen stores are depleted, causing
      the body to turn to gluconeogenesis as an energy substrate for galactopoiesis.
      The authors describe the case of a breastfeeding woman admitted to hospital and
      made nil per os (NPO) to treat a bowel obstruction. She did not receive
      intravenous glucose and 3 days postadmission developed a dangerous starvation
      ketosis (venous pH of 6.64). She was treated with intravenous dextrose,
      bicarbonate as well as cessation of breastfeeding and recovered quickly. Only
      four previous reports describe human lactation ketosis and this is the first
      iatrogenic case reported to our knowledge. It highlights the importance of
      addressing the unique caloric requirements of nursing women, especially when they
      are kept NPO.

PMID- 22605609
TI  - Topical dobesilate eye drops for ophthalmic primary pterygium.
AB  - Selective inhibition of fibroblast growth factor and vascular endothelial growth
      factor signalling pathways is effective in causing regression of pterygia. Prompt
      regression of fibrovascular mass and conjunctival angiogenesis was documented 2
      weeks after topical administration of dobesilate eye drops twice daily. At 3
      month follow-up, no recurrence was seen and no ocular irritation and burning were
      noted. The authors believe that this is the first known successful use of topical
      dobesilate in primary pterygium.

PMID- 22605610
TI  - Successful management of multi-focal hepatic infantile hemangioendothelioma using
      TACE/surgery followed by maintenance metronomic therapy.
AB  - Infantile hepatic hemangioendothelioma (IHE) is a rare angiogenic tumour with
      diverse clinical presentations and varied course ranging from spontaneous
      regression to life-threatening complications. The authors report a 2-year boy who
      presented with respiratory distress and was identified as a case of inoperable
      multi-focal hepatic IHE. He showed a transient response to trans-arterial-chemo
      embolisation and liver resection but had progressive disease despite chemotherapy
      (prednisolone/vicristine/ifosfamide/cisplatin). Thereafter, he was successfully
      managed with metronomic therapy using cyclophosphamide and tamoxifen.

PMID- 22605611
TI  - Preoperative hypoalbuminemia is associated with adverse outcomes after ileoanal
      pouch surgery.
AB  - BACKGROUND: This study examines the association between preoperative albumin and
      ileoanal pouch (IPAA) outcomes and the utility of serum albumin in the decision
      to perform a staged IPAA with an initial subtotal colectomy. METHODS: From 2001
      2009, patients were identified from an institutional pouch database and albumin
      values were extracted from the clinic data repository. Hypoalbuminemic (albumin
      <3.5 g/dL) patients were compared with patients with normal albumin. The primary
      outcome was pouch failure. Secondary outcomes were anastomotic leak, length of
      stay, function, and quality of life after pouch surgery. RESULTS: Out of 405
      patients, 34 were hypoalbuminemic pre-IPAA. Pre-IPAA hypoalbuminemia was
      associated with pouch failure (P = 0.004). Pre-IPAA hypoalbuminemia was an
      independent predictor of anastomotic leak (P = 0.017). Pre-IPAA hypoalbuminemia
      was an independent predictor of prolonged length of stay (LOS) (P < 0.001).
      Hypoalbuminemic patients who underwent index total proctocolectomy (TPC) with
      IPAA vs. subtotal colectomy (STC) and delayed IPAA had increased perioperative
      transfusion (P = 0.03) and median LOS at IPAA (P = 0.002). CONCLUSIONS:
      Preoperative serum albumin is an easily available, inexpensive marker in risk
      stratifying patients undergoing ileoanal pouch surgery. Serum albumin may provide
      an objective indicator in supporting the decision to undertake a subtotal
      colectomy as a first step rather than total proctocolectomy with immediate pouch
      creation.

PMID- 22605612
TI  - Prenatal diagnosis and outcome of absent pulmonary valve syndrome: contemporary
      single-center experience and review of the literature.
AB  - OBJECTIVE: To review the anomaly spectrum of prenatally detected absent pulmonary
      valve syndrome (APVS) and the outcome after diagnosis. Previous fetal studies
      reported survival rates of <= 25% for patients with intended postnatal care.
      METHODS: Clinical data and echocardiograms of 12 cases with a fetal diagnosis of
      APVS between 2000 and 2010 were analyzed in this retrospective single-center
      study. Collected parameters included: gestational age at referral, associated
      fetal abnormalities, cardiothoracic ratio, maximum diameters of pulmonary annulus
      and main and branch pulmonary arteries, ventricular dimensions and function as
      well as ventricular Doppler flows. Karyotyping included fluorescence in-situ
      hybridization (FISH) analysis for microdeletion 22q11.2. RESULTS: Median
      gestational age at diagnosis was 24 weeks. Three subtypes of APVS were observed:
      (1) with tetralogy of Fallot (TOF) and no arterial duct (n = 10; 83%); (2)
      isolated, with a large arterial duct (n = 1; 8%); and (3) with tricuspid atresia,
      right ventricular dysplasia and a restricted duct (n = 1; 8%). The cardiothoracic
      ratio and pulmonary artery dimensions were increased in all cases. The karyotype
      was abnormal in 70% of fetuses with TOF and their mortality rate was
      significantly higher due to pregnancy termination (n = 3) or perinatal demise (n
      = 2) (hazard ratio, 5; 95% CI, 0.87-28.9; P = 0.015). Of seven live births with
      active postnatal care, six children (86%) were alive without residual respiratory
      symptoms at a median follow-up of 4.7 (range, 2.1-10.6) years. CONCLUSION:
      Outcome after fetal diagnosis of APVS was significantly better in this study
      compared with those of previous fetal series, with a low mortality rate for
      actively managed patients.

PMID- 22605613
TI  - Neuropsychological aspects of childhood multiple sclerosis: an overview.
AB  - While cognitive impairment, major depression, and fatigue have been well
      documented in adult patients with multiple sclerosis (MS), there is still little
      information regarding MS-associated cognitive disabilities in infants and
      adolescents who represent 3 to 5% of all MS cases. Recent studies show that
      cognitive decline related to MS profoundly interferes with academic success and
      psychosocial adjustment. Neuropsychological dysfunction affects quality of life
      more significantly than mere Expanded Disability Status Scale is able to reflect.
      We herein give an overview of the knowledge available to date. Affective and
      emotional disturbances together with other comorbidities interfering with
      cognition are also reviewed. Finally, possible suggestions and future directions
      for the assessment of cognitive capabilities in children with MS are envisioned.

PMID- 22605614
TI  - Medulloblastoma in a child with fragile X syndrome.
AB  - Fragile X syndrome is the most common cause of inherited intellectual impairment
      and has been associated with decreased incidence of cancer. We present the case
      of an 11-year-old boy with a diagnosis of fragile X syndrome who presented with
      gait imbalance, headache, and episodes of vomiting. Radiological investigation
      revealed the presence of a posterior fossa tumor. The patient was operated upon
      and the tumor proved to be a medulloblastoma (MB). To the best of our knowledge
      this is the first reported case of MB in a child with fragile X syndrome.

PMID- 22605615
TI  - Effect of nonsolvent on the formation of polymer nanomaterials in the nanopores
      of anodic aluminum oxide templates.
AB  - We study the effect of nonsolvent on the formation of polymer nanomaterials in
      the nanopores of porous templates. Water (nonsolvent) is added into a poly
      (methyl methacrylate) (PMMA) solution in dimethylformamide (DMF) confined in the
      nanopores of an anodic aluminum oxide (AAO) template. Water forms a wetting layer
      on the pore wall and causes the PMMA solution to be isolated in the center of the
      nanopore, resulting in the formation of PMMA nanospheres or nanorods after the
      solvent is evaporated. The formation of the polymer nanomaterials induced by
      nonsolvent is found to be driven by the Rayleigh-instability-type transformation.
      Without adding the nonsolvent, PMMA chains precipitate on the walls of the
      nanopores after the solvent is evaporated, and PMMA nanotubes are obtained.

PMID- 22605616
TI  - Phase 1 dose-escalation trial evaluating the combination of the selective MET
      (mesenchymal-epithelial transition factor) inhibitor tivantinib (ARQ 197) plus
      erlotinib.
AB  - BACKGROUND: Amplification of the mesenchymal-epithelial transition factor (MET)
      gene can promote tumor resistance to epidermal growth factor receptor (EGFR)
      inhibition. Dual EGFR-MET inhibition may overcome this resistance. Tivantinib
      (ARQ 197) is a selective, oral, non-ATP-competitive, small-molecule inhibitor of
      the MET receptor tyrosine kinase. This phase 1 trial assessed the safety,
      pharmacokinetics, and preliminary antitumor activity of tivantinib combined with
      the EGFR inhibitor erlotinib. METHODS: Patients with advanced solid malignancies
      were administered oral tivantinib at escalating doses of 120, 240, 360, and 480
      mg twice daily (BID) plus 150 mg erlotinib once daily (QD). Single or multiple
      intrapatient dose escalation was planned in the absence of dose-limiting toxicity
      in the first cycle of therapy (21 days). RESULTS: Thirty-two patients received
      combination treatment. Tivantinib serum concentrations were not dose
      proportional. The most common (>= 20%) adverse events (AEs) regardless of
      causality included rash (n = 17), fatigue (n = 12), nausea (n = 10), abdominal
      pain (n = 10), diarrhea (n = 9), bradycardia (n = 9), and anemia (n = 7). AEs
      considered related to study treatment occurred in 28 patients (87.5%), and 5
      patients (15.6%) had treatment-related serious AEs, including neutropenia,
      leukopenia, syncope, sinus bradycardia, and sick sinus syndrome. Fifteen of 32
      patients (46.8%) had a partial response (n = 1) or stable disease (n = 14) as
      assessed by Response Evaluation Criteria in Solid Tumors. Six of 8 patients with
      nonsmall cell lung cancer achieved stable disease. The recommended phase 2 dose
      is tivantinib 360 mg BID plus erlotinib 150 mg QD. CONCLUSIONS: Tivantinib plus
      erlotinib was well tolerated with encouraging clinical activity, especially in
      patients with nonsmall cell lung cancer.

PMID- 22605617
TI  - Elastic and piezoelectric properties of zincblende and wurtzite crystalline
      nanowire heterostructures.
AB  - The elastic and piezoelectric properties of zincblende and wurtzite crystalline
      InAs/InP nanowire heterostructures have been studied using electro-elastically
      coupled continuum elasticity theory. A comprehensive comparison of strains,
      piezoelectric potentials and piezoelectric fields in the two crystal types of
      nanowire heterostructures is presented. For each crystal type, three different
      forms of heterostructures-core-shell, axial superlattice, and quantum dot
      nanowire heterostructures-are considered. In the studied nanowire
      heterostructures, the principal strains are found to be insensitive to the change
      in the crystal structure. However, the shear strains in the zincblende and
      wurtzite nanowire heterostructures can be very different. All the studied
      nanowire heterostructures are found to exhibit a piezoelectric field along the
      nanowire axis. The piezoelectric field is in general much stronger in a wurtzite
      nanowire heterostructure than in its corresponding zincblende heterostructure.
      Our results are expected to be particularly important for analyzing and
      understanding the properties of epitaxially grown nanowire heterostructures and
      for applications in nanowire electronics, optoelectronics, and biochemical
      sensing.

PMID- 22605618
TI  - Autism and the grand challenges in global mental health.

PMID- 22605620
TI  - In a state of flux: the energetic pathways that move contaminants from aquatic to
      terrestrial environments.

PMID- 22605621
TI  - Unrecognized causative factors for the lack of in vitro metabolism reported by
      McKinney et al.

PMID- 22605623
TI  - Local injection of infliximab in symptomatic isolated mucosal lesions: a novel
      scenario for endoscopic therapy?

PMID- 22605619
TI  - Neuroanatomy of melanocortin-4 receptor pathway in the lateral hypothalamic area.
AB  - The central melanocortin system regulates body energy homeostasis including the
      melanocortin-4 receptor (MC4R). The lateral hypothalamic area (LHA) receives
      dense melanocortinergic inputs from the arcuate nucleus of the hypothalamus and
      regulates multiple processes including food intake, reward behaviors, and
      autonomic function. By using a mouse line in which green fluorescent protein
      (GFP) is expressed under control of the MC4R gene promoter, we systemically
      investigated MC4R signaling in the LHA by combining double immunohistochemistry,
      electrophysiology, and retrograde tracing techniques. We found that LHA MC4R-GFP
      neurons coexpress neurotensin as well as the leptin receptor but do not coexpress
      other peptide neurotransmitters found in the LHA including orexin, melanin
      concentrating hormone, and nesfatin-1. Furthermore, electrophysiological
      recording demonstrated that leptin, but not the MC4R agonist melanotan II,
      hyperpolarizes the majority of LHA MC4R-GFP neurons in an ATP- sensitive
      potassium channel-dependent manner. Retrograde tracing revealed that LHA MC4R-GFP
      neurons do not project to the ventral tegmental area, dorsal raphe nucleus,
      nucleus accumbens, and spinal cord, and only limited number of neurons project to
      the nucleus of the solitary tract and parabrachial nucleus. Our findings provide
      new insights into MC4R signaling in the LHA and its potential implications in
      homeostatic regulation of body energy balance.

PMID- 22605624
TI  - Efficient polymerization of azide and active internal alkynes.
AB  - The 1,3-dipolar cycloaddition of azides and active internal alkynes has been well
      studied, but is rarely utilized as a tool for polymer preparation. In this work,
      an efficient polymerization route is developed. Polycycloaddition of diazide (4)
      and bis(benzoylethynyl)-benzenes and -butane (3) at elevated temperature has
      produced the first examples of soluble 1,4,5-trisubstituted polytriazoles PI with
      satisfactory molecular weights (M(w)  up to 16 400) in excellent yields (up to
      98.6%). All the obtained polymers are thermally stable, losing merely 5% of their
      weights at temperatures higher than 367  degrees C. They exhibit higher
      refractive indices than some commercial plastics and can be crosslinked upon UV
      irradiation to generate a 3D photopattern with high resolution. The metal-free
      feature of such a methodology offers a facile tool to prepare functional
      materials free from the contamination of metal species.

PMID- 22605625
TI  - Scalable fabrication of strongly textured organic semiconductor micropatterns by
      capillary force lithography.
AB  - Strongly textured organic semiconductor micropatterns made of the small molecule
      dioctylbenzothienobenzothiophene (C(8)-BTBT) are fabricated by using a method
      based on capillary force lithography (CFL). This technique provides the C(8)-BTBT
      solution with nucleation sites for directional growth, and can be used as a
      scalable way to produce high quality crystalline arrays in desired regions of a
      substrate for OFET applications.

PMID- 22605626
TI  - [Selecting the first drug in children and adolescents with epilepsy: evidence
      versus personal experience].
AB  - A first antiepileptic drug in children and adolescents can be selected at random,
      under the influence of the promotional strategies of pharmaceutical companies,
      based on the clinical trials that lead to its commercialisation, with the
      conclusions from meta-analyses, on evidence-based medicine, on open studies
      conducted after commercialisation, on expert consensus guidelines or based on
      personal experience. After reviewing all these procedures, the author deems
      personal experience to be the ideal method, provided that it involves a broad,
      long personal experience based on a preferential dedication to the basic,
      clinical, neurophysiological, pharmacological and therapeutic aspects of
      epilepsy.

PMID- 22605628
TI  - [Therapeutic update in tuberous sclerosis complex: the role of mTOR pathway
      inhibitors].
AB  - Tuberous sclerosis complex is an autosomal dominant disease, with variable
      expressivity and multisystemic involvement, which is characterised by the growth
      of benign tumours called hamartomas. The organs that are most commonly affected
      are the brain, skin, kidneys, eyes, heart and lungs. Of all the children with
      this disease, 85% present neurological manifestations that, due to their
      severity, are the main cause of morbidity and mortality. The most significant
      neurological manifestations are epilepsy, autism spectrum disorders and mental
      retardation. It has been shown that in tuberous sclerosis complex the genes TSC1
      and TSC2 alter the mTOR enzyme cascade, which sets off inhibition of this
      pathway. The possibility of resorting to treatments applied at the origin, thus
      inhibiting this pathway, is currently being evaluated.

PMID- 22605629
TI  - [Diagnostic and therapeutic update in narcolepsy].
AB  - Narcolepsy is an emblematic, unique disease within sleep disorders that is
      characterised by excessive daytime sleepiness, cataplexy and other abnormal
      manifestations of REM sleep. In the last 14 years truly spectacular progress has
      been made in our knowledge of this disease, since the discovery of its cause,
      i.e. a loss of the hypothalamic neurons that synthesise hypocretin, a previously
      unknown neurotransmitter, and its probable aetiopathogenic mechanisms, i.e. an
      autoimmune process in a patient with very precise immunological characteristics -
      a specific type of HLA and a specific type of T-cell receptor. The cause of this
      autoimmune process remains unknown. The definitive treatment - the administration
      of hypocretin, which is the substance missing in the organism - is still
      unavailable, but there are powerful drugs for treating its main symptoms, the
      sleepiness and the cataplexy. Some of these are classic compounds
      (methylphenidate, clomipramine), while others are more recent (modafinil,
      venlafaxine, sodium oxybate), but together they allow many patients to experience
      significant improvements. Lack of knowledge about the disease, both on the part
      of patients and their relatives as well as physicians, is the reason for the
      great delay in its diagnosis, with even more dramatic consequences when the
      disease begins in infancy.

PMID- 22605630
TI  - [Treatment with antisense oligonucleotides in Duchenne's disease].
AB  - In this paper I review the results of the treatments directed to modify the mRNA
      of dystrophin with the goal of converting the severe Duchenne type to the milder
      Becker muscular dystrophy. Antisense oligomers potential to modify Duchenne
      muscular dystrophy (DMD) gene expression and therapeutic strategies to induce
      ribosomal read-through of nonsense mutations (PTC124) are described. They are an
      important advance in the treatment of DMD, so far unspecific. Significant
      expression of new dystrophin is observed in biopsies of peripheral muscle,
      although the functional improvement is not so encouraging. New modification of
      chemistries are expected to improve the liberation, broad distribution in
      muscles, as well as their efficacy and safety enough to allow a positive chronic
      treatment of DMD.

PMID- 22605631
TI  - [Pharmacological update in attention deficit hyperactivity disorder: models of
      intervention and new drugs].
AB  - INTRODUCTION. Attention deficit hyperactivity disorder (ADHD) is the most
      frequent neurodevelopmental problem in childhood, with significant repercussions
      that continue into adulthood. This means that an appropriate therapeutic
      intervention is vital to improve its prognosis. AIMS. To identify the ideal
      pharmacological options according to the characteristics of the patient and to
      report on the new drugs. DEVELOPMENT. The work analyses how therapeutic
      interventions can be conditioned by the anatomical substrate of the brain, the
      biochemical bases, genetics, neurophysiological examinations, neuropsychological
      studies and the clinical symptoms and subtypes. A significant amount of
      importance is granted to neuropsychological studies, especially those dealing
      with the executive functions, including evaluation of attention, impulse control,
      and interference and cognitive flexibility. Taking into consideration the signal
      to-noise characteristics can be useful when it comes to choosing the drug.
      CONCLUSIONS. The development of the pharmacological therapeutic options in ADHD
      opens up expectations concerning applicability and greater specificity in daily
      practice to fit the characteristics of each patient. Psychoeducation must always
      be included and a thorough study of each particular child is recommended. This
      should involve analysing the neuropsychological features of his or her brain
      function in order to be able to reflect on the ideal pharmacological option that
      allows more favourable progress.

PMID- 22605632
TI  - [Cases of video electroencephalogram: differential diagnosis in newborn infants].
AB  - This study addresses a number of general considerations on epilepsies and
      epileptic syndromes that develop in the neonatal period. The chronological limits
      of this stage of maturation are set out and the pathophysiology of the convulsive
      phenomenon during that period are briefly analysed. Furthermore, the differences
      that exist as a result of the incipient level of maturity of the newborn infant's
      central nervous system with regard to other ages, and obviously adults, are
      highlighted. Likewise, reference is made to the percentage values of this
      pathology, which even vary depending on the gestational age. The clinical
      expression has a personality that is very different from the other stages of
      maturation in children, with four predominant manifestations: subtle, tonic,
      clonic and myoclonic seizures, which have been universally accepted since they
      were first reported by Volpe. Epilepsies in the newborn infant are not
      sufficiently well differentiated in the different classifications of epilepsies
      and epileptic syndromes that have appeared in recent years, although they could
      well be, since they display enough significance and individuality for that to be
      so. Three clinical cases are reported, with the aid of video
      electroencephalographic findings, to illustrate some of the possible neonatal
      epileptic manifestations.

PMID- 22605633
TI  - [Video electroencephalographic diagnosis of epileptic and non-epileptic
      paroxysmal episodes in infants and children at the pre-school age].
AB  - The main usefulness of video electroencephalographic (video-EEG) monitoring lies
      in the fact that it allows proper classification of the type of epileptic seizure
      and epileptic syndrome, identification of minor seizures, location of the
      epileptogenic zone and differentiation between epileptic seizures and non
      epileptic paroxysmal manifestations (NEPM). In infants and pre-school age
      children, the clinical signs with which epileptic seizures are expressed differ
      to those of older children, seizures with bilateral motor signs such as epileptic
      spasms, tonic and myoclonic seizures predominate, and seizures with interruption
      of activity or hypomotor seizures, and no prominent automatisms are observed. In
      children with focal epilepsies, focal and generalised signs are often superposed,
      both clinically and in the EEG. NEPM may be benign transitory disorders or they
      can be episodic symptoms of different neurological or psychopathological
      disorders. NEPM are often observed in children with mental retardation,
      neurological compromise or autism spectrum disorders, who present epileptic
      seizures and epileptiform abnormalities in the baseline EEG. It then becomes
      necessary to determine which episodes correspond to epileptic seizures and which
      do not. The NEPM that are most frequently registered in the video-EEG in infants
      and pre-school age children are unexpected sudden motor contractions ('spasms'),
      introspective tendencies, motor stereotypic movements and paroxysmal sleep
      disorders.

PMID- 22605635
TI  - [A critical analysis of the new classification of epilepsies and epileptic
      seizures of the International League Against Epilepsy (ILAE)].
AB  - The classification of epilepsies and epileptic syndromes currently in use dates
      back to the eighties. Around thirty years later, it is now time to look for new
      approaches that are better adapted to the numerous advances that have taken place
      over the years in the different areas of research on epilepsy (genetics,
      neuroimaging, neurophysiology, etc.). In response to repeated calls by different
      authors to modify the classical approaches to epilepsy, in the year 2010 the
      Commission on Classification and Terminology of the International League Against
      Epilepsy (ILAE), led by Berg, published a terminological and conceptual revision
      of epileptic seizures and epilepsies with recommendations regarding the direction
      to be followed in their classification. This article, however, has received a
      great deal of criticism because it proposes a radical change with the elimination
      of classical concepts, without maintaining the useful elements and modifying only
      the parts that reflect obsolete concepts in the light of current scientific
      evidence. Unnecessary confusion has been generated by, for example, eliminating
      the division between focal and generalised epilepsies, but keeping the concept of
      focal and generalised epileptic seizures or by proposing a classification that
      mixes different approaches, electroclinical criteria, aetiology, and so on. Thus,
      the ILAE has before it the important task of striking a balance between the
      different opinions that have arisen and offering a new, more moderate proposal.
      At this point it would do well to recall the words of Seneca, who warned of the
      dangers of not proceeding in that way when he said: 'everything that exceeds the
      bounds of moderation has an unstable foundation'.

PMID- 22605637
TI  - Reliability of fetal thymus measurement in prediction of 22q11.2 deletion: a
      retrospective study using four-dimensional spatiotemporal image correlation
      volumes.
AB  - OBJECTIVES: To evaluate the thymic-thoracic ratio (TT-ratio) method in assessment
      of the fetal thymus in normal fetuses and in those with cardiac abnormalities, in
      the presence or absence of 22q11.2 deletion. METHOD: Database records were
      reviewed for cases of conotruncal and arch abnormalities found on fetal
      echocardiography between January 2007 and September 2011. The 22q11.2 deletion
      status was retrieved and cases in which this was not known were excluded from the
      analysis, as were fetuses with aneuploidy or other genetic disorders. An
      additional 55 normal fetuses were analyzed as a control group. The TT-ratio was
      measured retrospectively using stored spatiotemporal image correlation (STIC)
      volume datasets. RESULTS: Sixty-nine fetuses with relevant cardiac diagnoses were
      identified and, of these, 18 (26%) had 22q11.2 deletion. The mean gestational age
      at diagnosis was 22 weeks. Significant pairwise differences, but also overlap,
      were observed between all three groups (i.e. fetuses with heart defects with and
      without the 22q11.2 deletion and controls). The mean TT-ratio was 0.44 in our
      normal control group and was significantly smaller in fetuses with 22q11.2
      deletion, corresponding to previously published data. However, the mean TT-ratio
      in the group with conotruncal anomalies but without the 22q11.2 deletion was also
      smaller than that in controls, in contrast to previously published data. The TT
      ratio was above the normal mean, regardless of fetal karyotype, in all cases of
      interrupted aortic arch. CONCLUSION: The TT-ratio method is a feasible and
      potentially useful tool during detailed fetal heart assessment. However, the
      absolute measurement is not reliable for prediction of 22q11.2 deletion and the
      obtained results should therefore be interpreted with caution. Fetal karyotyping
      should be recommended in cases with conotruncal heart abnormalities, irrespective
      of the TT-ratio.

PMID- 22605639
TI  - Long-term incidence of breast cancer by trial arm in one county of the Swedish
      Two-County Trial of mammographic screening.
AB  - BACKGROUND: This study estimated the excess incidence (overdiagnosis) of breast
      cancer associated with starting mammographic screening at an earlier age, by
      using data from the Dalarna County component of the Swedish Two-County Trial of
      breast cancer screening. METHODS: In Dalarna County, Sweden, 38,589 women aged 40
      to 74 years were randomized to invitation to regular mammographic screening
      (active study population [ASP]) and 18,582 women to usual care (passive study
      population [PSP]). After 3 screening rounds (6-8 years after randomization), the
      PSP was invited to screening. The cumulative incidence of breast cancer was
      calculated in the ASP and PSP from randomization to 29 years later. In addition,
      cumulative incidence was calculated for invasive cancers, advanced invasive
      cancers (>= 2 cm in maximum diameter or node-positive), and nonadvanced cancers
      (<2 cm and node negative). RESULTS: There was no excess of cancers in the ASP at
      29 year follow-up (relative risk, 1.00; 95% confidence interval, 0.92-1.08).
      Cumulative incidence in the 2 arms approximately equalized at the conclusion of
      the first round of screening of the PSP. There was an excess of nonadvanced
      cancers and a deficit of advanced cancers in the ASP, both of which persisted to
      29 years. CONCLUSIONS: There was no additional breast cancer incidence associated
      with 100,000 additional screens in the ASP. Results suggest that overdiagnosis is
      small and largely confined to the prevalence screen.

PMID- 22605638
TI  - Sex and the circuitry: progress toward a systems-level understanding of
      vertebrate sex determination.
AB  - In vertebrates, the gonad arises as a bipotential primordium that can
      differentiate as a testis or ovary. Cells are initially primed to adopt either
      fate by balanced antagonistic signaling pathways and transcription networks.
      Sexual fate is determined by activating the testis or ovarian pathway and
      repressing the alternative pathway. A complex, dynamic transcription network
      underlies this process, as approximately half the genome is being transcribed
      during this period, and many genes are expressed in a sexually dimorphic manner.
      This network is highly plastic; however, multiple lines of evidence suggest that
      many elements of the pathway converge on the stabilization or disruption of Sox9
      expression. The single gene mutational approach has led to the identification of
      ~30 additional genes involved in vertebrate sex determination. However, >50% of
      human disorders of sexual development (DSDs) are not explained by any of these
      genes, suggesting many critical elements of the system await discovery. Emerging
      technologies and genetic resources enable the investigation of the sex
      determination network on a global scale in the context of a variable genetic
      background or environmental influences. Using these new tools we can investigate
      how cells establish a bipotential state that is poised to adopt either sexual
      fate, and how they integrate multiple signaling and transcriptional inputs to
      drive a cell fate decision. Elucidating the genetic architecture underlying sex
      determination in model systems can lead to the identification of conserved
      modules correlated with phenotypic outcomes, and critical pressure points in the
      network that predict genes involved in DSDs in humans.

PMID- 22605640
TI  - Forebrain GABAergic projections from the dorsal raphe nucleus identified by using
      GAD67-GFP knock-in mice.
AB  - The dorsal raphe nucleus (DR) contains serotonergic (5-HT) neurons that project
      widely throughout the forebrain. These forebrain regions also receive innervation
      from non-5-HT neurons in the DR. One of the main groups of non-5-HT neurons in
      the DR is gamma-aminobutyric acid (GABA)ergic, but their projections are poorly
      understood due to the difficulty of labeling these neurons immunohistochemically.
      To identify GABAergic projection neurons within the DR in the current study, we
      used a knock-in mouse line in which expression of green fluorescent protein (GFP)
      is controlled by the glutamic acid decarboxylase (GAD)67 promotor. Projections of
      GAD67-GFP neurons to the prefrontal cortex (PFC), nucleus accumbens (NAC), and
      lateral hypothalamus (LH) were evaluated by using retrograde tract tracing. The
      location of GAD67-GFP neurons projecting to each of these areas was mapped by
      rostrocaudal and dorsoventral location within the DR. Overall, 16% of DR neurons
      projecting to either the PFC or NAC were identified as GAD67-GFP neurons. GAD67
      GFP neurons projecting to the PFC were most commonly found ventrally, in the
      rostral two-thirds of the DR. NAC-projecting GAD67-GFP neurons had an overlapping
      distribution that extended dorsally. GAD67-GFP neurons made a larger contribution
      to the projection of the DR to the LH, accounting for 36% of retrogradely labeled
      neurons, and were widespread throughout the DR. The current data indicate that DR
      GABAergic neurons not only may have the capacity to influence local network
      activity, but also make a notable contribution to DR output to multiple forebrain
      targets. J. Comp. Neurol. 520:4157-4167, 2012. (c) 2012 Wiley Periodicals, Inc.

PMID- 22605641
TI  - Topical treatment with the Toll-like receptor agonist DIMS0150 has potential for
      lasting relief of symptoms in patients with chronic active ulcerative colitis by
      restoring glucocorticoid sensitivity.
AB  - BACKGROUND: Patients with chronic active ulcerative colitis (UC) are regarded as
      treatment failures and represent an area of high unmet medical need, as normally
      the only remaining option is colectomy. METHODS: We treated a total of eight
      chronic active severe UC outpatients with the immunomodulatory agent DIMS0150 as
      an add-on to current therapies. Seven patients received a single topical dose of
      30 mg and one special case subject received three doses with 4 weeks between
      dosing occasions. All patients were classed as treatment failures and were
      elected for colectomy. Efficacy evaluation was determined in terms of colitis
      activity index, endoscopic improvement, and histologic disease activity assessed
      primarily at week 12 with a follow-up period of over 2 years. Glucocorticoid
      sensitivity was assayed by in vitro measurement of interleukin 6. RESULTS: All
      patients demonstrated a pronounced and rapid reduction in their colitis activity
      index within 1 week following a single intracolonic administration via
      colonoscope of the agent DIMS0150. Further improvements were evident at week 4,
      resulting in a clinical response rate for the single-dose treatment of 71%, with
      43% in clinical remission. By week 12 the clinical response and remission rates
      had reached 82% and 71%, respectively. A follow-up period of over 2 years
      posttreatment indicated that all but one of the treated patients had avoided the
      need for colectomy, with the longest patient being in symptom-free remission for
      over 27 months. Treatment with DIMS0150 restored glucocorticoid sensitivity.
      CONCLUSIONS: DIMS0150 may have the potential to be an effective agent to treat
      chronic active UC patients with the prospect to avoid colectomy on a long-term
      basis and is currently the subject of a clinical phase III study (EudraCT number:
      2011-003130-14).

PMID- 22605642
TI  - Hybrid organic/inorganic optical up-converter for pixel-less near-infrared
      imaging.

PMID- 22605643
TI  - Decreased hospital stay and significant cost savings after routine use of
      prophylactic gastrostomy for high-risk patients with head and neck cancer
      receiving chemoradiotherapy at a tertiary cancer institution.
AB  - BACKGROUND: Evidence-based nutritional and swallowing guidelines were developed
      to identify patients at high risk of developing malnutrition during
      chemoradiation for head and neck cancer. These guidelines recommended a
      prophylactic gastrostomy and were actively implemented at our institution in
      January 2007. This study assesses the effect of this policy change on patient
      outcomes. METHODS: This retrospective cohort study was carried out for the years
      before (2005) and after (2007) implementation of these guidelines. RESULTS: In
      all, 165 patients were treated with radical chemoradiation for head and neck
      cancer at our institution in the years 2005 and 2007. Gastrostomy tube
      complications were low. Patients in 2007 had significantly fewer hospital
      admissions, unexpected admissions, and a shorter mean duration of hospital stay
      in comparison with those in 2005. CONCLUSIONS: Prophylactic gastrostomy tubes in
      patients with high-risk head and neck cancer resulted in a significant decrease
      in hospital admissions and length of stay, and led to increased bed availability.

PMID- 22605644
TI  - Differentiation of human embryonic stem cells to cardiomyocytes on microcarrier
      cultures.
AB  - We have developed an improved cardiomyocyte differentiation protocol where we
      stabilized embryoid bodies (EB) in serum- and insulin-free medium (bSFS)
      supplemented with p38 MAP kinase inhibitor (SB203580) by addition of 10 um
      laminin-coated positively charged (protamine sulfate derivatized TSKgel Tresyl
      5PW) microcarriers. This protocol achieved a maximum 3-fold cell expansion,
      differentiation efficiency of 20%, and an overall cardiomyocyte yield of 3 * 105
      CM/ml in static conditions. In comparison, EB cultures achieved 1.5-fold cell
      expansion, differentiation efficiency of 15%, and an overall cardiomyocyte yield
      of 1.1 * 105 CM/ml. The scalability of this platform was demonstrated in
      suspended spinner cultures, producing a maximum of 2.14 * 105 CM/ml in 50-ml
      cultures. This yield is two-fold higher than the control static EB-based platform
      (1.1 * 105 CM/ml), and seven-fold higher than yields reported in literature, 3.1
      9 * 104 CM/ml. The robustness of this protocol was tested with HES-3 and H1 cell
      lines.

PMID- 22605645
TI  - Single and dual birthdating procedures for assessing the response of adult neural
      stem cells to the infusion of a soluble factor using halogenated thymidine
      analogs.
AB  - The factors that regulate the switch from adult neural stem cell (aNSC)
      quiescence to active proliferation are poorly understood. Here we describe a
      method to study the in vivo effect of a soluble factor on cell cycle entry and
      proliferation of aNSCs located in the brain neurogenic niches. First, we provide
      information for implanting osmotic minipumps that will deliver the compound of
      interest directly into the mouse brain. When combined with the administration of
      the thymidine analog bromodeoxyuridine (BrdU), this technique is the most basic
      procedure to study the effects of a soluble factor on aNSC proliferation. We also
      describe a dual replication labeling protocol using two different halogenated
      thymidine analogs, chloro- and iododeoxyuridine (CldU and IdU), that allows
      tracking of proliferating cells and assessing cell cycle re-entry of aNSCs at
      different time points.

PMID- 22605646
TI  - In vitro generation of three-dimensional substrate-adherent embryonic stem cell
      derived neural aggregates for application in animal models of neurological
      disorders.
AB  - In vitro-differentiated embryonic stem (ES) cells comprise a useful source for
      cell replacement therapy, but the efficiency and safety of a translational
      approach are highly dependent on optimized protocols for directed differentiation
      of ES cells into the desired cell types in vitro. Furthermore, the
      transplantation of three-dimensional ES cell-derived structures instead of a
      single-cell suspension may improve graft survival and function by providing a
      beneficial microenvironment for implanted cells. To this end, we have developed a
      new method to efficiently differentiate mouse ES cells into neural aggregates
      that consist predominantly (>90%) of postmitotic neurons, neural progenitor
      cells, and radial glia-like cells. When transplanted into the excitotoxically
      lesioned striatum of adult mice, these substrate-adherent embryonic stem cell
      derived neural aggregates (SENAs) showed significant advantages over transplanted
      single-cell suspensions of ES cell-derived neural cells, including improved
      survival of GABAergic neurons, increased cell migration, and significantly
      decreased risk of teratoma formation. Furthermore, SENAs mediated functional
      improvement after transplantation into animal models of Parkinson's disease and
      spinal cord injury. This unit describes in detail how SENAs are efficiently
      derived from mouse ES cells in vitro and how SENAs are isolated for
      transplantation. Furthermore, methods are presented for successful implantation
      of SENAs into animal models of Huntington's disease, Parkinson's disease, and
      spinal cord injury to study the effects of stem cell-derived neural aggregates in
      a disease context in vivo.

PMID- 22605647
TI  - High-efficiency transfection and siRNA-mediated gene knockdown in human
      pluripotent stem cells.
AB  - This unit describes a protocol on how to achieve high transfection efficiency on
      human embryonic stem cells and induced pluripotent stem cells using the common
      transfection reagent Lipofectamine 2000 as a carrier instead of involving a
      virus, and/or expensive equipment and reagents. Applying this technique for siRNA
      mediated gene targeting to knockdown genes in the pluripotent stem cells, the
      expression of pluripotent genes, such as OCT4 and LIN28, was downregulated by
      more than 90% in multiple pluripotent cell lines. Beyond reaching high
      transfection efficiency on pluripotent cells, this protocol should also have
      application to primary cells that are traditionally difficult to transfect.

PMID- 22605648
TI  - Excision of a viral reprogramming cassette by delivery of synthetic Cre mRNA.
AB  - The generation of patient-specific induced pluripotent stem (iPS) cells provides
      an invaluable resource for cell therapy, in vitro modeling of human disease, and
      drug screening. To date, most human iPS cells have been generated with
      integrating retro- and lenti-viruses and are limited in their potential utility
      because residual transgene expression may alter their differentiation potential
      or induce malignant transformation. Alternatively, transgene-free methods using
      adenovirus and protein transduction are limited by low efficiency. This unit
      describes a protocol for the generation of transgene-free human induced
      pluripotent stem cells using retroviral transfection of a single vector, which
      includes the coding sequences of human OCT4, SOX2, KLF4, and cMYC linked with
      picornaviral 2A plasmids. Moreover, after reprogramming has been achieved, this
      cassette can be removed using mRNA transfection of Cre recombinase. The method
      described herein to excise reprogramming factors with ease and efficiency
      facilitates the experimental generation and use of transgene-free human iPS
      cells.

PMID- 22605649
TI  - Can angle of progression in pregnant women before onset of labor predict mode of
      delivery?
AB  - OBJECTIVES: The angle of progression (AOP), measured by transperineal ultrasound,
      has been used to assess fetal head descent during labor. Our aim was to assess
      whether, before onset of labor, parous women have a narrower AOP than do
      nulliparous women and if a narrow AOP is associated with a higher rate of
      Cesarean delivery. METHODS: In this prospective, observational study, we
      performed transperineal ultrasound in pregnant women not yet in labor at >= 39
      weeks' gestation who delivered within 1 week of sonography. The AOP was compared
      as follows: in nulliparous women, between those who had a Cesarean section and
      those who delivered vaginally; and among women who delivered vaginally, between
      those who were nulliparous and those who were parous. RESULTS: Included in the
      study were 100 nulliparous and 71 parous women. Among those who delivered
      vaginally (n = 161), the median AOP before onset of labor was narrower in parous
      than in nulliparous women (98 degrees  (interquartile range (IQR)), 90-107
      degrees  vs 104 degrees  (IQR, 97-113 degrees ), P < 0.001). Among the 100
      nulliparous women, (1) the median AOP before onset of labor was narrower in those
      who went on to deliver by Cesarean section (n = 9) than in those delivered
      vaginally (n = 91) (90 degrees  (IQR, 85.5-93.5 degrees ) vs 104 degrees  (IQR,
      97-113 degrees ), P < 0.001); (2) an AOP >= 95 degrees  (derived from the
      receiver-operating characteristics curve) was associated with vaginal delivery in
      99% of women; and (3) 89% (8/9) of women who delivered by Cesarean section had an
      AOP < 95 degrees . Among the 71 parous women, only one delivered by Cesarean
      section and all of those with an AOP < 95 degrees  delivered vaginally.
      CONCLUSION: A narrow AOP (< 95 degrees ) in non-laboring nulliparous women at
      term is associated with a high rate of Cesarean delivery. Parous women have a
      narrower AOP than do nulliparous women before the onset of labor; however, unlike
      in nulliparous women, a narrow AOP in parous women does not appear to be
      associated with Cesarean delivery and most parous women with such an angle go on
      to deliver vaginally.

PMID- 22605650
TI  - Tivantinib (ARQ 197), a selective inhibitor of MET, in patients with
      microphthalmia transcription factor-associated tumors: results of a multicenter
      phase 2 trial.
AB  - BACKGROUND: Microphthalmia transcription factor (MITF)-associated (MiT) tumors
      are a family of rare malignancies, including alveolar soft part sarcoma (ASPS),
      clear cell sarcoma (CCS), and translocation-associated renal cell carcinoma
      (tRCC) that have dysregulated expression of oncogenic MITF family proteins. The
      MET receptor tyrosine kinase gene is transcriptionally activated by MITF family
      proteins, making MET a potential therapeutic target for MiT tumors. This study
      assessed the activity of tivantinib (ARQ 197), a selective MET inhibitor, in
      patients with MiT-associated tumors. METHODS: This multicenter, single-arm, phase
      2 trial enrolled patients with advanced MiT tumors. Patients initially received
      tivantinib 120 mg orally twice daily, then 360 mg twice daily per protocol
      amendment. The primary endpoint was overall response rate. Secondary endpoints
      included safety, progression-free survival, pharmacokinetics, and correlative
      studies. RESULTS: A total of 47 patients (median age, 25 years; range, 11-73
      years) with ASPS (n = 27), CCS (n = 11), tRCC (n = 6), or other tumor types (n =
      3) were enrolled. Common grade 3/4 drug-related adverse events included anemia
      (4%) and neutropenia (4%). Three patients (6.4%) experienced 4 treatment-related
      serious adverse events (grade 3 febrile neutropenia, thrombocytopenia, and deep
      vein thrombosis, and grade 4 thrombocytopenia). Best response was partial
      response in 1 CCS patient (2%) and stable disease in 28 patients (60%). Median
      progression-free survival was 3.6 months (overall), 5.5 months (ASPS), and 1.9
      months (CCS and tRCC). Baseline MET expression was strongly or focally positive
      in tumor samples from 14 of 19 patients (74%). CONCLUSIONS: Tivantinib was safe
      and tolerable in patients with MiT tumors, but antitumor activity was modest.

PMID- 22605651
TI  - Altering membrane topology with Sar1 does not impair spindle assembly in Xenopus
      egg extracts.
AB  - Intracellular membrane networks including the endoplasmic reticulum (ER) and the
      Golgi apparatus experience dramatic reorganization upon entry into mitosis.
      However, the mechanisms driving these rearrangements and their importance for
      cell division are poorly understood. The GTPase Sar1 is a component of the
      secretory pathway and a key activator of anterograde transport of cargo from the
      ER to the Golgi. Here we show that Sar1 mutant proteins added to metaphase
      arrested Xenopus laevis egg extracts cause dramatic effects on membrane
      organization. Live analysis of membrane structures in egg extract cytoplasm
      revealed a distinct network of sheets and tubules reflective of the organization
      of the ER in other systems. Addition of a constitutively active Sar1 GTPase
      mutant (H79G) increased membrane tubulation, while a dominant negative version
      Sar1 (T39N) impaired tubule organization. Although microtubule pelleting assays
      revealed that Sar1 associates with microtubules in the egg extract, and addition
      of Sar1 (H79G) mutant slightly destabilized spindle poles, bipolar spindle
      assembly was largely unaffected. Thus, spindles are stable to dramatic changes in
      mitotic membrane organization at metaphase, suggesting that mitotic membrane is
      not an upstream regulator of the mitotic spindle apparatus in Xenopus egg
      extracts.

PMID- 22605652
TI  - Head and neck soft tissue sarcomas: unique lack of significance of synchronous
      node metastases.
AB  - BACKGROUND: Regional lymph node metastasis (RLNM) has been identified as a poor
      prognostic indicator for patients with soft tissue sarcomas (STS) of the
      extremities and trunk. However, the effect of RLNM on survival in patients with
      STS of the head and neck (HN) has not previously been explored. Our objective was
      to analyze RLNM as a prognostic indicator in HN-STS, and to compare this cohort
      to patients with STS of non-head and neck regions (NHN-STS). METHODS: STS
      patients were identified using the Surveillance, Epidemiology, and End Results
      database. Only patients without concurrent distant metastasis who underwent
      surgery and pathologic node staging were included. Patients were categorized
      based on tumor location: (1) HN-STS and (2) NHN-STS. Clinicopathologic data and
      disease-specific survival (DSS) were compared between node-negative and node
      positive patients in each group. RESULTS: We identified 183 cases of node
      positive STS (25 HN-STS, 158 NHN-STS). In the HN-STS group, pN1 status was not
      associated with any of the clinicopathologic factors that we analyzed. DSS was
      similar among pN0 and pN1 patients with HN-STS (P = 0.59); however, in the NHN
      STS group, node-positivity was significantly associated with disease-specific
      mortality (P < 0.001). CONCLUSIONS: Synchronous RLNM may not affect DSS in
      patients HN-STS. Node-positive patients with HN-STS appear to be unique from
      those with NHN-STS.

PMID- 22605653
TI  - Head and neck squamous cell carcinoma: differentiation of histologic grade with
      standard- and high-b-value diffusion-weighted MRI.
AB  - BACKGROUND: The correlation between the histologic grades and the apparent
      diffusion coefficient (ADC) in head and neck squamous cell carcinomas (HNSCCs)
      remains unclear. This study aimed to evaluate the potential of diffusion-weighted
      MRI (DW-MRI) at both standard and high b values to differentiate the histologic
      grades of HNSCC. METHODS: In all, 54 consecutive patients with HNSCCs (34 well
      differentiated, 10 moderately differentiated, and 10 poorly differentiated)
      performed DW-MRIs at both b = 1000 and 2000 s/mm(2) prior to biopsy or surgery.
      The ADC values were compared among the different histologic grades. RESULTS: The
      ADC values of well-differentiated and poorly differentiated HNSCC were
      significantly different at both b values (p < .001 in both). However, significant
      difference between moderately differentiated and poorly differentiated HNSCC was
      revealed at only b = 2000 s/mm(2) (p = .014). CONCLUSIONS: DW-MRIs at standard
      and high b values are helpful for differentiating histologic grades in HNSCC with
      better differentiation at a high b-value.

PMID- 22605654
TI  - High-performance membranes with multi-permselectivity for CO2 separation.
AB  - Multi-permselective membranes with diffusivity-selectivity, solubility
      selectivity, and reactivity-selectivity for CO(2)  separation are prepared by
      interfacial polymerization. The membranes are able to efficiently separate CO(2) 
      from various light gases (H(2) , CH(4)  and N(2) ) due to the optimized membrane
      structure and the comprehensive utilization of distinctions between CO(2)  and
      light gases in size, condensability, and reactivity.

PMID- 22605655
TI  - Evaluation of responsive gene expression as a sensitive and specific biomarker in
      patients with ulcerative colitis.
AB  - BACKGROUND: Clinical trials in ulcerative colitis (UC) rely on certain parameters
      to evaluate responses that are highly subjective or of low sensitivity. Here,
      using a select group of genes, we tested the accuracy of gene expression analysis
      as a biomarker of clinical, endoscopic, and histologic improvements. METHODS:
      Intestinal biopsies were obtained from UC patients included in two cohorts.
      Cohort 1 was used to select for genes whose expression was modulated in active
      (vs. inactive) UC. Cohort 2 included patients recruited in a phase II study
      receiving placebo, mesalazine, or dersalazine sodium for 4 weeks. The expression
      of 44 genes identified in Cohort 1 was assessed at weeks 0 and 4, and was then
      correlated with biomarkers, as well as with clinical, endoscopic, and histologic
      scores. RESULTS: Significant changes in the expression of 31 of the 44 genes
      tested were detected in Cohort 2 at week 4. Gene expression (DeltaCt)
      significantly correlated with the total Mayo score, C-reactive protein (CRP), and
      fecal calprotectin. The number of genes significantly regulated at week 4 was
      highly associated with histologic and endoscopic responses. Logistic regression
      analysis identified four separate genes (IFITM1, ITGB2, IL1R2, IL2RA) whose
      relative change was independently associated with endoscopic remission with high
      specificity and sensitivity. CONCLUSIONS: Change in the expression of a select
      set of genes can serve as an early biomarker, one with high specificity and
      sensitivity to clinical, endoscopic, and histologic responses. This could
      represent a new tool for identifying early response to treatment in mild to
      moderately active UC patients.

PMID- 22605656
TI  - Pulmonary outflow tract obstruction in fetuses with complex congenital heart
      disease: predicting the need for neonatal intervention.
AB  - OBJECTIVE: To identify prenatal echocardiographic markers that could predict the
      need for neonatal intervention in fetuses with right ventricular outflow tract
      obstruction. METHODS: This was a retrospective study of 52 fetuses with right
      ventricular outflow tract obstruction. Echocardiograms were evaluated for fetuses
      with either two-ventricle anatomy with a large ventricular septal defect or
      single-ventricle anatomy. Fetuses with pulmonary atresia were excluded.
      Parameters were compared between groups that did and did not require an
      intervention at age < 30 days. RESULTS: Fifty-two fetuses were studied; 20 (38%)
      underwent neonatal intervention and 32 (62%) did not. The most common diagnosis
      was tetralogy of Fallot (n = 32). Fetuses with two ventricles that required an
      intervention had lower pulmonary valve diameter Z-score (PV-Z-score) (-4.8 +/-
      2.1 vs. -2.6 +/- 1.1; P = 0.0002) and lower pulmonary valve to aortic valve
      annular diameter ratio (PV/AoV) (0.53 +/- 0.15 vs. 0.66 +/- 0.1; P = 0.003).
      Using a PV/AoV ratio of < 0.6 or a PV-Z-score of < -3 at final echocardiographic
      examination was highly sensitive (92%) but poorly specific (50%), whereas
      classifying direction of flow in the ductus arteriosus as either normal (all
      pulmonary-to-aorta) or abnormal (aorta-to-pulmonary or bidirectional) was both
      highly sensitive (100%) and specific (95%) for predicting the need for a neonatal
      intervention. Parameters for the single-ventricle cohort did not reach
      statistical significance. CONCLUSIONS: Analysis of the pulmonary outflow tract
      and ductus arteriosus flow in the fetus with complex congenital heart disease can
      aid in identifying those that will require a neonatal intervention to augment
      pulmonary blood flow. This has important implications for the planning of
      delivery strategies.

PMID- 22605657
TI  - Treg cells to the rescue.

PMID- 22605658
TI  - Development and validation of a symptom index for advanced hepatobiliary and
      pancreatic cancers: the National Comprehensive Cancer Network Functional
      Assessment of Cancer Therapy (NCCN-FACT) Hepatobiliary-Pancreatic Symptom Index
      (NFHSI).
AB  - BACKGROUND: The 45-item Functional Assessment of Cancer Therapy-Hepatobiliary
      (FACT-Hep) questionnaire assesses health-related quality of life in patients with
      liver, bile duct, and pancreatic cancers. Although the FACT-Hep was initially
      derived from patient input, this study's researchers sought to verify adequate
      coverage of items by soliciting open-ended input from patients with advanced
      disease. METHODS: As part of a larger study in collaboration with the National
      Comprehensive Cancer Network (NCCN), 50 people (60% male, 80% caucasian, average
      age 60.4 years) with stage 3 or 4 hepatobiliary or pancreatic cancer were
      recruited. Participants generated and ranked up to 10 important symptoms and
      concerns that physicians should monitor when assessing the value of chemotherapy.
      Patients were also able to provide open-ended, qualitative information that was
      evaluated systematically. Ten expert physicians also provided input on priority
      symptoms. RESULTS: The resulting 18-item NCCN-FACT Hepatobiliary-Pancreatic
      Symptom Index (NFHSI-18) demonstrated high internal consistency (alpha = .89) and
      moderate to strong correlations with measures of physical well-being (rho = .76),
      emotional well-being (rho = 0.52), and functional well-being (rho = 0.57). Scores
      on the NFHSI-18 were also highly correlated with the original hepatobiliary scale
      of the FACT-Hep (rho = .82; all P < .001). Compared with patients with better
      performance status, patients with poor performance status had worse NFHSI-18
      symptom scores, F(3,47) = 9.74; P = .0003. CONCLUSIONS: The NFHSI-18 assesses
      symptoms of importance to patients with hepatobiliary and pancreatic cancers and
      demonstrates promising measurement properties. The scale is a good candidate for
      brief symptom assessment in clinical trials.

PMID- 22605659
TI  - Structure and activity of full-length formin mDia1.
AB  - Formins are a conserved family of actin assembly-promoting factors with essential
      and diverse biological roles. Most of our biochemical understanding of formin
      effects on actin dynamics is derived from studies using formin fragments. In
      addition, all structural information on formins has been limited to fragments.
      This has left open key questions about the structure, activity and regulation of
      intact formin proteins. Here, we isolated full-length mouse mDia1 (mDia1-FL) and
      found that it forms tightly autoinhibited dimers that can only be partially
      activated by RhoA. We solved the structure of autoinhibited mDia1-FL using
      electron microscopy and single particle analysis. Docking of crystal structures
      into the three dimensional reconstruction revealed that the fork-shaped N
      terminal diaphanous inhibitory domain-coiled coil domain region hangs over the
      ring-shaped formin homology (FH)2 domain, suggesting that autoinhibition results
      from steric obstruction of actin binding. Deletion of the C-terminal diaphanous
      autoregulatory domain extended mDia1 structure and activated it for actin
      assembly. Using total internal reflection fluorescence microscopy, we observed
      that RhoA-activated mDia1-FL persistently accelerated filament elongation in the
      presence of profilin similar to mDia1 FH1-FH2 fragment. These observations
      validate the known activities of FH1-FH2 fragments as reflecting those of the
      intact molecule. Our results further suggest that mDia1-FL does not readily snap
      back into the autoinhibited conformation and dissociate from growing filament
      ends, and thus additional factors may be required to displace formins and
      restrict filament length.

PMID- 22605660
TI  - Stro-1(+)  stromal cells have stem-like features in giant cell tumor of bone.
AB  - BACKGROUND: Giant cell tumor of bone (GCTB) is an aggressive benign bone tumor
      with poor prognosis whose neoplastic component is stromal cells (SCs). Tumor stem
      like cells (TSCs) have been demonstrated as precursors for tumor genesis and
      growth. The aim of this study is to identify TSCs in GCTB. METHODS: Stro-1(+) and
      Stro-1(-) cells were isolated by fluorescence-activated cell sorting (FACS). Stem
      like properties of both Stro-1(+) and Stro-1(-) subpopulations were assessed
      using MTT colorimetric assays, cell cycle analyses, sphere formation assays, and
      differentiation assays. Molecular profiles were analyzed by flow cytometry,
      immunofluorescence, and qRT-PCR. RESULTS: The existence of rare Stro-1(+) cells
      was confirmed in vitro using FACS and in vivo by immunohistochemistry. These Stro
      1(+) cells exhibited higher proliferative and cisplatin-resistant potentials than
      Stro-1(-) cells. In serum-free suspension cultures, Stro-1(+) SCs could form cell
      spheres and maintain self-renewal. Furthermore, Stro-1(+) SCs could differentiate
      into two mesenchymal lineage cells: osteoblasts and adipocytes. Cell surface
      markers CD44, CD117, and CD133 and stem cell-associated genes OCT3/4, NANOG, and
      ABCG2 were significantly higher in the Stro-1(+) subpopulation. CONCLUSIONS: This
      study demonstrates that Stro-1(+) SCs in GCTB possess stem-like biological and
      molecular phenotypes, indicating that they are the TSCs of GCTB.

PMID- 22605661
TI  - Safety and effectiveness of long-term allopurinol-thiopurine maintenance
      treatment in inflammatory bowel disease.
AB  - BACKGROUND: Thiopurines are the mainstay of conventional maintenance therapy in
      inflammatory bowel disease (IBD). Unfortunately, up to 50% of patients
      discontinue immunosuppressive therapy within 2 years due to intolerance or lack
      of efficacy. Allopurinol with low-dose thiopurine can optimize thiopurine
      metabolism for IBD patients with preferential shunting toward 6-methyl
      mercaptopurine (6-MMP) formation. The aim of this study was to assess long-term
      maintenance effectiveness and tolerability of allopurinol-thiopurine therapy in a
      larger multicenter cohort of IBD patients. METHODS: Enrolled patients who failed
      monotherapy with thiopurines due to a skewed metabolism were subsequently treated
      with a combination therapy of allopurinol and low-dose thiopurine. Adverse events
      were monitored and therapeutic adherence was assessed. Seventy-seven IBD patients
      were enrolled with a mean follow-up of 19 months. RESULTS: The median 6
      thioguanine nucleotide concentration increased from 145 during monotherapy to 271
      pmol/8 * 10(8) red blood cell (RBC) after at least 8 weeks of combination therapy
      while reducing the thiopurine dosage (P < 0.001). In contrast, median 6-MMP
      concentrations decreased from 10,110 to 265 pmol/8 * 10(8) RBC (P < 0.001).
      Leukopenia occurred in 12 patients (16%), requiring dose adaptation. Liver test
      abnormalities normalized in 81% of patients after the addition of allopurinol.
      Sixteen (21%) patients had to discontinue combination therapy. The percentage of
      patients still using combination therapy at 6, 12, 24, and 60 months was 87%,
      85%, 76%, and 65%, respectively. CONCLUSIONS: Long-term combination therapy with
      allopurinol and low-dose thiopurines is an effective and well-tolerated treatment
      in IBD patients with a skewed thiopurine metabolism.

PMID- 22605662
TI  - Prospective study of prognostic value of Raf kinase inhibitory protein and
      pretreatment plasma Epstein-Barr virus DNA for distant metastasis in
      locoregionally advanced nasopharyngeal carcinoma.
AB  - BACKGROUND: The purpose of this prospective study was to investigate the
      predictive significance of Raf kinase inhibitory protein (RKIP) in locoregionally
      advanced nasopharyngeal carcinoma (NPC) and its effect on distant metastasis.
      METHODS: The usual immunohistochemical stainings were performed to detect RKIP
      expression of cancer tissues from 210 patients with advanced NPC. After DNA
      samples from pretreatment plasma from these patients were extracted, real-time
      polymerase chain reaction (PCR) was performed to quantitatively analyze plasma
      Epstein-Barr virus (EBV) DNA. RESULTS: RKIP expression was significantly
      different for different N classifications and WHO pathologic grades, respectively
      (p < .05). Cox regression confirmed RKIP and EBV DNA were independent prognostic
      markers for 5-year distant metastasis-free survival (DMFS). In the high RKIP
      expression group, chemotherapy had a positive effect on improved DMFS, but not in
      the low RKIP expression group. CONCLUSIONS: RKIP could be identified as an
      independent prognostic factor on DMFS. For each combined treatment modality, the
      different impact of chemotherapy on distant metastasis might be related to the
      RKIP expression level.

PMID- 22605663
TI  - An extremely simple thermocouple made of a single layer of metal.
AB  - A novel temperature sensor consisting of a single layer of metal (Ni, Pd, W, or
      Pt) is constructed. Its configuration challenges a long-established concept and
      may lead to development of a new category of devices. Reliable two-dimensional
      mapping of local temperatures is demonstrated using an array of these sensors.
      These single-metal thermocouples (SMTCs) can be readily applied on flexible
      substrates or at high temperatures.

PMID- 22605664
TI  - Lateral ventricles in fetuses with aneuploidies at 11-13 weeks' gestation.
AB  - OBJECTIVE: To examine the possible association between aneuploidies and fetal
      lateral cerebral ventriculomegaly in the first trimester of pregnancy. METHODS:
      Three-dimensional brain volumes were acquired by transvaginal ultrasound
      examination at 11-13 weeks' gestation in 410 euploid fetuses and 63 fetuses with
      trisomy 21, 34 with trisomy 18 and seven with trisomy 13. Lateral ventricles were
      assessed in a transverse view, just above the roof of the third ventricle and
      measurements of the areas of the lateral ventricles and choroid plexuses were
      obtained. The ratio between choroid plexus and lateral ventricle areas (CLR) was
      calculated. Measurements in aneuploid fetuses were compared to those in euploid
      fetuses. RESULTS: In euploid fetuses the lateral ventricle and choroid plexus
      areas increased, whereas the CLR decreased with fetal biparietal diameter. In
      fetuses with trisomy 21, lateral ventricle and choroid plexus areas were smaller
      but CLR was not significantly different from that in euploid fetuses. In trisomy
      18 and 13 fetuses, CLR was significantly smaller than in euploid fetuses. The CLR
      was below the 5(th) centile of normal range in 11 (32.4%) fetuses with trisomy 18
      and in six (85.7%) with trisomy 13. CONCLUSION: There is evidence of
      ventriculomegaly at 11-13 weeks' gestation in most fetuses with trisomy 13 and
      one third of fetuses with trisomy 18.

PMID- 22605665
TI  - The prostate cancer conundrum revisited: treatment changes and prostate cancer
      mortality declines.
AB  - BACKGROUND: Prostate cancer mortality rates in the United States declined by >40%
      between 1991 and 2005. The impact of changes in primary treatment and adjuvant
      and neoadjuvant hormone therapy on this decline is unknown. METHODS: The authors
      applied 3 independently developed models of prostate cancer natural history and
      disease detection under common assumptions about treatment patterns, treatment
      efficacy, and survival in the population. Primary treatment patterns were derived
      from the Surveillance, Epidemiology, and End Results registry; data on the
      frequency of hormone therapy were obtained from the CaPSURE (Cancer of the
      Prostate Strategic Urologic Research Endeavor) database; and treatment efficacy
      was based on estimates from randomized trials and comparative effectiveness
      studies of treatment alternatives. The models projected prostate cancer mortality
      without prostate-specific antigen screening and in the presence and absence of
      treatment benefit. The impact of primary treatment was expressed as a fraction of
      the difference between observed mortality and projected mortality in the absence
      of treatment benefit. RESULTS: The 3 models projected that changes in treatment
      explained 22% to 33% of the mortality decline by 2005. These contributions were
      accounted for mostly by surgery and radiation therapy, which increased in
      frequency until the 1990s, whereas hormone therapies contributed little to the
      mortality decline by 2005. Assuming that treatment benefit was less for older
      men, changes in treatment explained only 16% to 23% of the mortality decline by
      2005. CONCLUSIONS: Changes in primary treatment explained a minority of the
      observed decline in prostate cancer mortality. The remainder of the decline
      probably was because of other interventions, such as prostate-specific antigen
      screening and advances in the treatment of recurrent and progressive disease.

PMID- 22605666
TI  - One-step interfacial synthesis and assembly of ultrathin luminescent AuNPs/silica
      membranes.
AB  - A facile one-step strategy is explored to achieve uniform luminescent Au
      nanoparticles (AuNPs) in a two-dimensional ultrathin silica matrix based on
      simultaneous reaction and assembly at the liquid-liquid interface. The as
      prepared AuNPs/silica nanocomposites can be further employed to fabricate
      micrometer-thick films with bifunctional luminescent and superhydrophobic
      properties. Such a versatile concept is ideal for the development of
      multifunctional devices.

PMID- 22605667
TI  - The role of small GTPases in neuronal morphogenesis and polarity.
AB  - The highly dynamic remodeling and cross talk of the microtubule and actin
      cytoskeleton support neuronal morphogenesis. Small RhoGTPases family members have
      emerged as crucial regulators of cytoskeletal dynamics. In this review we will
      comprehensively analyze findings that support the participation of RhoA, Rac,
      Cdc42, and TC10 in different neuronal morphogenetic events ranging from migration
      to synaptic plasticity. We will specifically address the contribution of these
      GTPases to support neuronal polarity and axonal elongation.

PMID- 22605668
TI  - Older age is associated with higher rate of discontinuation of anti-TNF therapy
      in patients with inflammatory bowel disease.
AB  - BACKGROUND: In increasingly aging populations, awareness of outcomes of older
      patients treated with biologics is becoming more important. However, few studies
      to date have investigated the safety and durability of anti-tumor necrosis factor
      (TNF) therapy in this subgroup. METHODS: This was a retrospective single-center
      study with cases comprising all IBD patients who began anti-TNF treatment at age
      >60 years. Cases of Crohn's disease (CD) and ulcerative colitis (UC) were
      identified from medical record review. Our controls consisted of patients younger
      than age 60 years on anti-TNF treatment and patients >60 years on treatment with
      immunomodulators. Kaplan-Meier survival estimates were used to calculate the
      probability of remaining on anti-TNF therapy. RESULTS: We identified a total of
      54 IBD patients who initiated anti-TNF therapy over the age of 60 years (mean 73,
      range 61-97 years). Among these, a total of 38 patients (70%) discontinued anti
      TNF therapy after a mean of 24.1 months. At 12 months after initiation, 75% of
      patients older than age 60 years were still on anti-TNF agents compared to 93%
      among younger users and 82% among older AZA users (P < 0.05). Compared to older
      AZA users, older anti-TNF users remained more likely to require early therapy
      cessation (hazard ratio 2.21, 95% confidence interval 1.29-3.78). CONCLUSIONS:
      The IBD population older than age 60 at the time of initiation of anti-TNF
      therapy is at higher risk for discontinuation of therapy. They may also be
      particularly vulnerable to infectious complications requiring hospitalization,
      suggesting the need for careful monitoring during therapy.

PMID- 22605669
TI  - Value of general surgical risk models for predicting postoperative liver failure
      and mortality following liver surgery.
AB  - BACKGROUND AND OBJECTIVES: This study evaluated the ability of general surgical
      models to predict postoperative morbidity and mortality in liver surgery.
      METHODS: The postoperative course and mortality rates predicted by general
      surgical models were investigated in 960 patients who underwent hepatectomy or
      ablation therapy for primary or metastatic liver carcinoma. RESULTS: The area
      under the receiver operative characteristic curve (95% confidence intervals) for
      detecting postoperative liver failure was 0.89 (0.84-0.94), 0.85 (0.78-0.92), and
      0.78 (0.72-0.85) for the estimation of physiologic ability and surgical stress (E
      PASS) model, the modified E-PASS (mE-PASS) model, and the Portsmouth Physiologic
      and Operative Severity Score for the enUmeration of Mortality and morbidity (P
      POSSUM) model, respectively, and those for detecting in-hospital mortality were
      0.85 (0.76-0.93), 0.85 (0.78-0.92), and 0.79 (0.71-0.87), respectively.
      Nevertheless, all of the models overpredicted the overall mortality rate (by 2.3
      fold for E-PASS, 2.3-fold for mE-PASS, and 2.9-fold for P-POSSUM). CONCLUSIONS:
      The general surgical risk models demonstrated high discriminatory power for
      predicting postoperative outcomes in liver surgery, but overpredicted the overall
      mortality rate by more than twofold. Therefore, these models should be refined to
      make them more suitable for predicting liver surgery outcomes.

PMID- 22605671
TI  - Comprehensive expression profiling of microRNAs in laryngeal squamous cell
      carcinoma.
AB  - BACKGROUND: MicroRNAs (miRNAs) are noncoding RNAs involved in posttranscriptional
      regulation of gene expression in cancer and provide new perspectives on the
      development of laryngeal squamous cell carcinoma (SCC). METHODS: miRNA expression
      of 6 pairs of laryngeal SCC and adjacent normal tissues was screened using miRNA
      array. Laser capture microdissection was applied to isolate a homogeneous group
      of cells from laryngeal SCC samples. The results of miRNA array analysis were
      validated in 48 pairs of laryngeal SCC and adjacent normal tissues using
      quantitative RT-PCR. RESULTS: Twenty-nine differentially expressed miRNAs were
      detected in the 6 pairs of laryngeal SCC, of which 6 were confirmed, including
      upregulation of miR-21, miR-93, miR-205, and miR-708 and downregulation of miR
      125b and miR-145. Their putative target genes were predicted using 3 online
      software programs. CONCLUSION: These differentially expressed miRNAs may play a
      role in tumorigenesis and progression in laryngeal SCC and offer new angles for
      further investigations into the function of miRNAs.

PMID- 22605672
TI  - The economic impact of a patient navigator program to increase screening
      colonoscopy.
AB  - BACKGROUND: Patient navigation can increase colorectal cancer screening rates.
      The net economic impact of a colonoscopy patient navigator program was evaluated
      in an urban public hospital setting. METHODS: Cost, cost-effectiveness, and cost
      benefit analyses were performed of a colonoscopy patient navigation program at 3
      urban public hospitals in the period from 2003 to 2007. Program effectiveness was
      assessed in a 2-group, pre- and post-program, nonrandomized evaluation, comparing
      program hospitals with comparison hospitals that served similar populations.
      Costs were assessed from the provider's perspective. Outcomes included
      colonoscopy volume, colonoscopy completion rate, program cost, incremental cost
      effectiveness, and net monetary benefit. RESULTS: Patient navigation was
      associated with a 61% increase in average monthly colonoscopy volume at program
      hospitals, from 114 procedures to 184 procedures, compared with a 12% increase at
      comparison hospitals. Adjusted for other factors, the navigator program increased
      colonoscopy volume by 44 to 67 additional procedures per month. Average program
      cost varied from $50 to $300 per patient referred to a navigator. Incremental
      cost-effectiveness varied from $200 to $700 per additional colonoscopy. At 2
      hospitals, net revenue associated with increased colonoscopy volume exceeded the
      program cost per additional colonoscopy, yielding a net financial benefit; at the
      third hospital, the program yielded a net cost. Variation between hospitals in
      the program's economic impact was primarily attributable to differences in
      personnel costs. CONCLUSIONS: Economic evaluation of this colonoscopy patient
      navigator program in an urban public hospital setting suggests that such programs
      can be a cost-effective use of limited resources and yield a net financial
      benefit for providers.

PMID- 22605673
TI  - Poor recall of prior exposure to varicella zoster, rubella, measles, or mumps in
      patients with IBD.
AB  - BACKGROUND: Few studies have measured the levels of antibodies specific for
      measles, mumps, rubella, and varicella zoster/chickenpox viruses in inflammatory
      bowel disease (IBD) patients undergoing treatment with
      immunomodulators/biologics. METHODS: We prospectively recruited 139 IBD
      outpatients. Enzyme-linked immunosorbent assays were used as the serological
      tests for measles, mumps, rubella, and varicella zoster. We defined anti-rubella
      IgG < 10 IU/mL, anti-measles IgG < 16 IU/mL, and anti-mumps/varicella zoster IgG
      <4 IU/mL as seronegative for viruses. We also asked participants about past
      immunizations against or infections with measles, mumps, rubella, and varicella
      zoster viruses. RESULTS: The proportion of patients with seronegative levels of
      antibodies specific for varicella zoster, rubella, measles, and mumps viruses was
      5%, 30%, 34%, and 37%, respectively. Approximately 40% of the IBD patients did
      not remember whether they had previously been infected with any of the viruses,
      and almost one-third of the patients could not remember whether they had
      previously been vaccinated. Almost 30% of the patients with a past history of
      rubella or measles did not have seropositive antibody levels. A total of 54% of
      the patients being treated with immunosuppressant displayed seronegative levels
      of antibodies specific for at least one of the viruses. CONCLUSIONS: Many IBD
      patients were unaware of whether they had previously been vaccinated against or
      infected with the viruses causing varicella zoster, rubella, measles, or mumps.
      Therefore, measuring the current levels of antibodies specific for such viruses
      is useful for determining whether patients have seropositive antibody levels
      before immunomodulators/biologics are used for therapy.

PMID- 22605674
TI  - High resolution optical spectroscopy of air-induced electrical instabilities in n
      type polymer semiconductors.
AB  - We use high-resolution charge-accumulation optical spectroscopy to measure charge
      accumulation in the channel of an n-type organic field-effect transistor. We
      monitor the degradation of device performance in air, correlate the onset voltage
      shift with the reduction of charge accumulated in the polymer semiconductor, and
      explain the results in view of the redox reaction between the polymer, water and
      oxygen in the accumulation layer.

PMID- 22605675
TI  - Occult metastases detected by sentinel node biopsy in patients with early oral
      and oropharyngeal squamous cell carcinomas: impact on survival.
AB  - BACKGROUND: Analysis of the lymphatic drainage pattern, the reliability of a
      negative sentinel lymph node biopsy (SLNB), as well as the impact of sentinel
      lymph node (SLN) metastases on regional control and survival in patients with
      early stage oral and oropharyngeal squamous cell carcinoma (SCC). METHODS: A
      prospective consecutive cohort analysis was conducted which included 111 patients
      diagnosed between 2003 and 2010. Endpoints of the study were neck control rate,
      overall survival (OS), disease-specific survival (DSS), and disease-free survival
      (DFS), depending on the size of occult metastases. RESULTS: Forty-nine of 111
      patients (38%) had positive SLNs, 10 had isolated tumor cells (ITCs), 19 had
      micrometastases, and 13 had macrometastases. OS, DSS, and DFS at 3 years for SLN
      negative and SLN-positive patients was 98% and 71%, 95% and 76%, and 98% and 73%,
      respectively. Furthermore, there was a statistically significant difference
      between the SLN-negative group and ITCs in DSS as well as between the SLN
      negative group and patients with micrometastases in OS and DSS and between the
      SLN-negative group and patients with macrometastases in all 3 survival estimates.
      CONCLUSION: Our study is the first to demonstrate that even small tumor deposits
      only detectable by the extensive histopathologic workup of the SLNB protocol have
      a significant impact on tumor control and survival in early Oropharyngeal SCC.
      Whether these findings will translate into different treatment strategies based
      on the upstaged neck has to be further investigated.

PMID- 22605676
TI  - Selective automation and skill transfer in medical robotics: a demonstration on
      surgical knot-tying.
AB  - BACKGROUND: Transferring non-trivial human manipulation skills to robot systems
      is a challenging task. There have been a number of attempts to design research
      systems for skill transfer, but the level of the complexity of the actual skills
      transferable to the robot was rather limited, and delicate operations requiring a
      high dexterity and long action sequences with many sub-operations were impossible
      to transfer. METHODS: A novel approach to human-machine skill transfer for multi
      arm robot systems is presented. The methodology capitalizes on the metaphor of
      'scaffolded learning', which has gained widespread acceptance in psychology. The
      main idea is to formalize the superior knowledge of a teacher in a certain way to
      generate support for a trainee. In our case, the scaffolding is constituted by
      abstract patterns, which facilitate the structuring and segmentation of
      information during 'learning by demonstration'. The actual skill generalization
      is then based on simulating fluid dynamics. RESULTS: The approach has been
      successfully evaluated in the medical domain for the delicate task of automated
      knot-tying for suturing with standard surgical instruments and a realistic
      minimally invasive robotic surgery system.

PMID- 22605677
TI  - Conventional transoral surgery for stage I-II squamous cell carcinoma of the
      tonsillar region.
AB  - BACKGROUND: The purpose of this study was to review the results of conventional
      transoral resection and neck dissection for stage I to II squamous carcinoma of
      the tonsillar region. METHODS: We conducted a retrospective review of 65 patients
      (stage I, 21 patients; stage II, 44 patients). Induction chemotherapy and
      postoperative radiation therapy (RT) were administered in 76.9% and 12.3%,
      respectively, of these cases. RESULTS: The postoperative course was uneventful in
      96.9% of patients. Five-year actuarial estimates for local recurrence, nodal
      recurrence, distant metastasis, and survival were 0% to 7.6%, 0% to 7.8%, 0% to
      7.3%, and 70.8% to 71.5% for patients with T1 to T2 carcinoma, respectively.
      Contralateral and retropharyngeal recurrence occurred in only 1 patient.
      CONCLUSION: Conventional transoral resection with ipsilateral neck dissection
      provides an alternative approach for patients with stage I to II squamous cell
      carcinoma (SCC) of the tonsillar region. A primary surgical approach spares the
      use of radiotherapy to eliminate late effects and to permit its use for
      subsequent management of metachronous head and neck second primary cancer.

PMID- 22605678
TI  - Ribonucleases P/MRP and the expanding ribonucleoprotein world.
AB  - One of the hallmarks of life is the widespread use of certain essential
      ribozymes. The ubiquitous ribonuclease P (RNase P) and eukaryotic RNase MRP are
      essential complexes where a structured, noncoding RNA acts in catalysis. Recent
      discoveries have elucidated the three-dimensional structure of the ancestral
      ribonucleoprotein complex, suggested the possibility of a protein-only
      composition in organelles, and even noted the absence of RNase P in a non-free
      living organism. With respect to these last two findings, import mechanisms for
      RNases P/MRP into mitochondria have been demonstrated, and RNase P is present in
      organisms with some of the smallest known genomes. Together, these results have
      led to an ongoing debate regarding the precise definition of how "essential"
      these ribozymes truly are.

PMID- 22605680
TI  - Comparing surgery and radiation in the treatment of oropharyngeal cancer.

PMID- 22605681
TI  - Prevalence, incidence and determinants of PTSD and other mental disorders: design
      and methods of the PID-PTSD+3 study.
AB  - Investigation of the prevalence, incidence, and determinants of post-traumatic
      stress disorders (PTSD) and other mental disorders associated with military
      deployment in international missions poses several methodological and procedural
      challenges. This paper describes the design and sampling strategies, instruments,
      and experimental procedures applied in a study programme aimed to examine
      military deployment-related mental health and disorders (prevalence and
      trajectories) and to identify vulnerability and risk factors (e.g. age, gender,
      type of mission, rank, and duration of deployment and a wide range of
      neurobiological, psychological, social, and behavioural factors). The study
      comprised two components. The first component, a cross-sectional study, included
      1483 deployed and 889 non-deployed German soldiers (response rate, 93%) who
      served during the 2009 International Security Assistance Force (ISAF) mission. A
      standardized diagnostic instrument (Composite International Diagnostic Interview,
      CIDI) coupled with established questionnaires was administered to detect and
      diagnose PTSD and a broad spectrum of mental disorders and mental health
      problems. The second component, a prospective-longitudinal study, included 621
      soldiers examined before (2011) and after return (2012) from the ISAF mission. In
      addition to the CIDI and questionnaires, several experimental behavioural tests
      and biological markers were implemented to probe for incident mental disorders,
      mental health problems and risk factors. Our methods are expected to provide
      greater precision than previous studies for estimating the risk for incident
      deployment-related and non-deployment-related disorders and their risk factors.
      We expect the findings to advance our understanding of a wide spectrum of adverse
      mental health outcomes beyond PTSD.

PMID- 22605682
TI  - Major adverse limb events and wound healing following infrapopliteal artery stent
      implantation in patients with critical limb ischemia: the XCELL trial.
AB  - BACKGROUND: Percutaneous transluminal angioplasty (PTA) with stent deployment of
      infrapopliteal arteries is an accepted but unproven therapy for patients with
      critical limb ischemia (CLI). We evaluated the safety and effectiveness of the
      XpertTM self-expanding nitinol stent (Abbott Vascular, Redwood City, CA) in
      Rutherford Class 4-6 subjects with infrapopliteal lesions of 4-15 cm in length.
      METHODS AND RESULTS: 120 patients (140 limbs, 212 implanted devices) underwent
      primary infrapopliteal nitinol stent deployment as part of this multicenter
      registry. The primary endpoint was 12-month amputation-free survival (AFS);
      secondary endpoints included limb salvage, target lesion revascularization (TLR),
      6- month angiographic patency, and 6- and 12-month outcomes of wound healing and
      pain relief. Despite a 6-month binary stent restenosis rate of 68.5%, the 12
      month AFS rate was 78.3%. Stratified according to baseline Rutherford classes 4,
      5 and 6, the 12-month AFS rates were 100%, 77.3%, and 55.2%, respectively, and
      freedom from major amputation rates were 100%, 90.9%, and 70.1%, respectively.
      The 12-month freedom from major amputation rate and clinically driven TLR were
      89.6% and 70.1%, respectively. The 6- and 12-month complete wound-healing rates
      were 49.0% and 54.4%, respectively. Rutherford class 4 patients had significant
      pain relief through 12-months (P<0.05). CONCLUSIONS: Primary infrapopliteal
      nitinol stenting to treat CLI is safe and effective in improving 6-and 12-month
      clinical outcomes.

PMID- 22605683
TI  - Prenatal stress changes learning strategies in adulthood.
AB  - It is well known that stressful experiences may shape hippocampus-dependent
      learning and memory processes. However, although most studies focused on the
      impact of stress at the time of learning or memory testing, very little is known
      about how stress during critical periods of brain development affects learning
      and memory later in life. In this study, we asked whether prenatal stress
      exposure may influence the engagement of hippocampus-dependent spatial learning
      strategies and caudate nucleus-dependent response learning strategies in later
      life. To this end, we tested healthy participants whose mothers had experienced
      major negative life events during their pregnancy in a virtual navigation task
      that can be solved by spatial and response strategies. We found that young adults
      with prenatal stress used rigid response learning strategies more often than
      flexible spatial learning strategies compared with participants whose mothers did
      not experience major negative life events during pregnancy. Individual
      differences in acute or chronic stress do not account for these findings. Our
      data suggest that the engagement of hippocampal and nonhippocampal learning
      strategies may be influenced by stress very early in life.

PMID- 22605684
TI  - Long-term outcome of transcatheter polytetrafluoroethylene-covered stent
      implantation in a giant coronary aneurysm of a child with Kawasaki disease.
AB  - We report the long-term outcome of a child with Kawasaki disease (KD), who had a
      giant aneurysm with stenotic lesions in the right coronary artery, resulting in
      the transcatheter implantation of a polytetrafluoroethylene (PTFE)-covered stent
      at the age of 8. Quantitative coronary angiography analysis later showed the
      increase of the diameter stenosis at both stent edges for the first 10 months
      after implantation; however, the stenosis did not develop thereafter. Coronary
      perfusion was still well maintained at follow-up coronary angiography 5.5 years
      after implantation (diameter stenosis was 36.5% at proximal and 37.4% at distal
      edge, respectively). Although further follow-up is necessary, the long-term
      outcome of a PTFE-covered stent implantation for a KD patient is satisfactory in
      this instance. Implantation of a covered stent in a giant aneurysm is considered
      a promising treatment option.

PMID- 22605685
TI  - Interaction of cyproheptadine hydrochloride with human serum albumin using
      spectroscopy and molecular modeling methods.
AB  - The interaction between cyproheptadine hydrochloride (CYP) and human serum
      albumin (HSA) was investigated by fluorescence spectroscopy, UV-vis absorption
      spectroscopy, Fourier transform infrared spectroscopy (FT-IR) and molecular
      modeling at a physiological pH (7.40). Fluorescence of HSA was quenched
      remarkably by CYP and the quenching mechanism was considered as static quenching
      since it formed a complex. The association constants Ka and number of binding
      sites n were calculated at different temperatures. According to Forster's theory
      of non-radiation energy transfer, the distance r between donor (human serum
      albumin) and acceptor (cyproheptadine hydrochloride) was obtained. The effect of
      common ions on the binding constant was also investigated. The effect of CYP on
      the conformation of HSA was analyzed using FT-IR, synchronous fluorescence
      spectroscopy and 3D fluorescence spectra. The thermodynamic parameters DeltaH and
      DeltaS were calculated to be -14.37 kJ mol(-1) and 38.03 J mol(-1) K(-1),
      respectively, which suggested that hydrophobic forces played a major role in
      stabilizing the HSA-CYP complex. In addition, examination of molecular modeling
      indicated that CYP could bind to site I of HSA and that hydrophobic interaction
      was the major acting force, which was in agreement with binding mode studies.

PMID- 22605686
TI  - Variation in the sensitivity of Callosobruchus (Coleoptera: Bruchidae)
      acetylcholinesterase to the organophosphate insecticide malaoxon: effect of
      species, geographical strain and food type.
AB  - BACKGROUND: Bruchid beetles, Callosobruchus species, are serious pests of
      economically important grain legumes; their activity in stores is often
      controlled by the use of synthetic insecticides. Esterases are known to be
      involved in insecticide resistance in insects. However, there is a dearth of
      information on esterase activity in the genus Callosobruchus. In this study, the
      effect of species, geographical strain and food type on the variation in
      acetylcholinesterase (AChE) activity and its inhibition by malaoxon (malathion
      metabolite) was investigated using an in vitro spectrophotometric method. RESULT:
      AChE activity varied significantly among species and strains and also among
      legume type used for rearing them. Generally, irrespective of species, strain or
      food type, the higher the AChE activity of a population, the higher is its
      inhibition by malaoxon. C. chinensis had the highest AChE activity of the species
      studied, and in the presence of malaoxon it had the lowest remaining AChE
      activity, while C. rhodesianus retained the highest activity. CONCLUSION: A first
      hand knowledge of AChE activity in regional Callosobruchus in line with the
      prevailing food types should be of utmost importance to grain legume breeders,
      researchers on plant materials for bruchid control and pesticide
      manufacturer/applicators for a robust integrated management of these bruchids.

PMID- 22605687
TI  - Temperament and living conditions: a comparison study of Poles and Koreans.
AB  - The present investigation tested the temperament traits of 319 Polish and 315
      South Korean students according to the regulative theory of temperament. Poland
      and South Korea are two countries with a similar rate of economic growth but with
      distinct cultures; for instance, they differ in terms of individualism and
      masculinity dimensions as well as living conditions. This means that they have
      achieved the same goal with different resources but presumably also with
      different side effects. The results indicate that the Poles had higher levels of
      briskness, sensor sensibility and endurance, as well as lower levels of emotional
      reactivity and perseveration in comparison with South Koreans. The structure of
      one's temperament determines one's ability to meet environmental requirements and
      also how one deals with stressful conditions. According to previous empirical
      data, Poles' temperament profile can be characterized as being less prone to
      stress perception and therefore more advantageous. It is possible that Koreans,
      as they have a less adaptive temperament structure, experience higher levels of
      stress in a more stimulating environment than Poles.

PMID- 22605688
TI  - Acute fibrinous and organising pneumonia.
AB  - Acute fibrinous and organising pneumonia (AFOP) was recently described as an
      unusual pattern of diffuse lung disease. Particular characteristics make the
      differential diagnosis with the well recognised clinical patterns of diffuse
      alveolar damage, cryptogenic organising pneumonia or eosinophilic pneumonia. The
      lack of hyaline membranes, the presence of intra-alveolar fibrin, absence of
      noticeable eosinophils and patchy distribution suggests that AFOP define a
      distinct histological pattern. The authors describe the case of a woman diagnosed
      with AFOP after surgical lung biopsy, in association with primary biliary
      cirrhosis. The patient presented dyspnoea, fatigue, dry cough and thoracic pain.
      The CT scan showed bilateral patchy infiltrates predominantly in the lower lobes.
      Flexible bronchoscopy and subsidiary techniques were inconclusive and biopsy
      through video-assisted thoracoscopic surgery led to anatomopathological diagnosis
      of AFOP. The patient is having a good clinical response to prednisone.

PMID- 22605689
TI  - A novel risk of air embolism with intravenous paracetamol.

PMID- 22605690
TI  - Calcified chronic subdural haematoma.
AB  - Chronic subdural haematoma (CSH) is a well-known disease entity; however,
      calcified CSH (CCSH) is quite rare. Here the authors report on a 65-year-old man
      who developed gradual left hemiparesis and had gradually deteriorating level of
      consciousness for 1 month. CT scan revealed a huge right-sided CCSH. He underwent
      surgery and the CCSH was excised totally. The patient recovered well and was able
      to do his daily activities by himself. Surgical treatment for CCSH results in
      good neurological outcome.

PMID- 22605691
TI  - Morbid obesity in a child with monosomy 1p36 syndrome.
AB  - The monosomy 1p36 syndrome is a cause of syndromic obesity. It is characterised
      by psychomotor delay, hypotonia and typical craniofacial dysmorphism. Other
      features commonly associated are behavioural anomalies including hyperphagia and
      self-injuring, seizures, congenital heart disease and hypothyroidism. The authors
      report the case of a 9-year and 5-month-boy referred to the paediatric
      endocrinology clinics for morbid obesity. Clinical findings were generalised
      obesity with a body mass index >95th centile, acanthosis nigricans of the neck,
      arms with self inflicted lesions, deep-set eyes, straight eyebrows, broad nasal
      bridge and pointed chin. He was unable to walk and had no expressive language.
      Cytogenetic analysis identified 1p36.33-pter deletion (~139 Mb terminal deletion
      in chromosome 1 short arm) and Y chromosome duplication. The blood analysis
      showed insulin resistance and dyslipidaemia. The authors emphasise the need to
      consider monosomy 1p36 as a cause of severe psychomotor delay and obesity.

PMID- 22605692
TI  - Cluster of neurological manifestations of rotavirus infection in children.
AB  - Rotavirus infection in children in the resource-rich countries is usually benign
      but complications are reported rarely. Four children presented within 4 weeks
      with neurological symptoms and stool virology positive for rotavirus. All four
      made a quick recovery and were discharged home after a few days without
      medication. At 6 weeks all were well, with no further neurological episodes. This
      is the first reported cluster of this nature. Potential mechanisms for how
      rotavirus causes its rare neurological complications are briefly discussed, along
      with clinical implications for clinicians managing such patients.

PMID- 22605693
TI  - Hepatic cyst infection in a healthy older male.
AB  - Simple hepatic cysts are usually asymptomatic and are not associated with
      impaired hepatic function. However, complications, such as obstructive jaundice,
      rupture, intracystic haemorrhage and infection, can occur. The authors describe
      the case of a 82-year-old man with fever and elevated C-reactive protein. A
      repeat contrast-enhanced abdominal CT scan revealed enlargement with peripheral
      enhancement in the left lateral segment of the liver. A diagnosis of infected
      hepatic cyst was made, and percutaneous transhepatic drainage of the cyst was
      performed. When a patient has liver cysts and high-grade fever, liver cysts
      should be considered as a focus of infection. Repetition of ultrasonography
      and/or CT studies should be considered, even if no typical findings are obtained
      initially. It is of note that conventional Ga-scintigraphy may be useful for the
      detection of infected site.

PMID- 22605694
TI  - Repair of rectus femoris rupture with LARS ligament.
AB  - The rectus femoris muscle is the most frequently involved quadriceps muscle in
      strain pathologies. The majority of quadriceps muscle belly injuries can be
      successfully treated conservatively and even significant tears in the less active
      and older population, non-operative management is a reasonable option. The
      authors report the delayed presentation of a 17-year-old male who sustained an
      injury to his rectus femoris muscle belly while playing football. This young
      patient did not recover the functional outcome required to get back to running
      and participating in sport despite 15 months of physiotherapy and non-operative
      management. Operative treatment using the ligament augmentation and
      reconstruction system ligament to augment Kessler repair allowed immediate full
      passive flexion of the knee and an early graduated physiotherapy programme. Our
      patient was able to return to running and his previous level of sport without any
      restrictions.

PMID- 22605695
TI  - The lady with a calcified brain.
AB  - The authors present here a case that demonstrates the importance of exclusion of
      metabolic conditions before giving a diagnosis of Fahr disease. This case also
      highlights the possibility of exacerbation of hypocalcaemia by antiepileptic
      agents.

PMID- 22605696
TI  - Transdermal hyoscine induced unilateral mydriasis.
AB  - The authors present a case of unilateral mydriasis in a teenager prescribed
      transdermal hyoscine hydrobromide (scopolamine) for chemotherapy induced nausea
      and vomiting. The authors discuss the ocular side-effects associated with this
      particular drug and delivery system and the potential use of transdermal hyoscine
      as an antiemetic agent in this group.

PMID- 22605697
TI  - CT findings in blast lung injury.

PMID- 22605698
TI  - An unusual cause for hyponatremia with seizures.
AB  - A 50-year-old Asian Indian female with known hypertension presented with
      persistent vomiting but no other symptoms of meningism. Clinical examination and
      basic laboratory parameters were entirely normal except for significant
      hyponatremia. Further investigation was suggestive of the syndrome of
      inappropriate antidiuretic hormone (SIADH) secretion. Subsequently, despite
      steady correction of hyponatremia, the patient developed generalised seizures.
      Cerebrospinal fluid (CSF) analysis performed was inconclusive. Screening for a
      chronic meningitis underlying SIADH, yielded positive blood and CSF titres for
      venereal disease research laboratory (VDRL), which were confirmed by Treponema
      pallidum haemagglutination (TPHA). The patient was treated for neurosyphilis and
      made a complete recovery. Hyponatremia resolved and she had no further episodes
      of seizures. She was tested for HIV infection which was negative. On follow-up,
      she remained TPHA positive but VDRL titres became negative.

PMID- 22605699
TI  - Bronchiolitis obliterans organising pneumonia syndrome presenting with
      neutrophilia in bronchoalveolar lavage fluid after breast-conserving therapy.
AB  - A 61-year-old female presented with a dry cough and fever 4 months after
      tangential radiation therapy (RT) following conserving surgery for breast cancer.
      Chest radiography and CT demonstrated consolidation with air bronchogram outside
      the irradiated area. Neutrophil granulocytes were abundant in bronchoalveolar
      lavage fluid (BALF) (39.6% of total cells), and transbronchial lung biopsy
      revealed organising pneumonia (OP) histologically. Antibiotic therapy had no
      effect, but corticosteroid therapy brought about clinical improvement. Her
      condition was diagnosed as bronchiolitis obliterans OP (BOOP) syndrome.
      Lymphocytic BALF has been identified as a characteristic of BOOP syndrome induced
      after RT for breast cancer. The BALF in this case, however, was neutrophilic. In
      our analysis of differential cell counts in the BALF of 24 patients with BOOP
      syndrome, the BALF was neutrophilic (>5%) in 16 (76%) cases, and the neutrophilia
      was severe in some of those patients.

PMID- 22605700
TI  - Appendiceal metastasis 10 years following 'curative' resection for low-grade
      primary endometrial carcinoma.
AB  - Metastasis of primary endometrial adenocarcinoma to unusual sites has been
      occasionally reported. However, the authors believe this to be the first case
      report of metastasis to the appendix. This occurred more than 10 years after
      curative resection, and presented as sepsis with an intra-abdominal focus.

PMID- 22605701
TI  - Severe congenital thrombocytopaenia--first clinical manifestation of Noonan
      syndrome.
AB  - This report focuses on a male infant, the first born of non-consanguineous
      parents diagnosed with polyhydramnios at 26 weeks of gestation. The newborn was
      admitted during the neonatal period with bleeding diathesis associated with a low
      platelet count at birth (5*10(9)/l).The authors registered a persistent low
      platelet count (9000-129 000/l) during the infants 1st year of life. Physical
      examination revealed a petechial rash, a dysmorphic face and bilateral
      cryptorchidism, in the absence of organomegaly. Additionally, cardiologic
      evaluation revealed an aortic valve dysplasia and an atrial septal defect, while
      bone marrow biopsy and aspiration were found normal. Throughout the
      investigation, the authors excluded congenital infection, alloimmune and familiar
      thrombocytopaenia, Fanconi anaemia and thrombocytopaenia absent radius syndrome.
      The cytogenetic analysis revealed a mutation in the PTPN11 gene associated with
      Noonan syndrome. Here the author highlights that severe neonatal
      thrombocytopaenia is a manifestation that should be considered in the diagnosis
      and clinical management of Noonan's syndrome.

PMID- 22605702
TI  - Ethical indications for radiological procedures: a clearer picture.
AB  - An 80-year-old gentleman presented with long-standing diarrhoea and weight loss.
      A large bowel malignancy was suspected but his co morbidity precluded major
      abdominal surgery. At the time of treatment CT colonography was not in common use
      and the investigation of choice was barium enema. Due to the invasive nature of
      this procedure the medical team decided it would not be in his best interests to
      subject him to further investigation. Uncertainty surrounding his diagnosis was
      distressing for him and his family who felt that a firm diagnosis would allow
      them to plan his ongoing care needs. The patient accepted the risks and underwent
      a barium enema that confirmed the presence of a large bowel carcinoma that was
      inoperable. The case highlights how application of the ethical principles can aid
      the decision making process in difficult scenarios and emphasises the importance
      of treating the individual and not the disease.

PMID- 22605703
TI  - Psychotic-affective symptoms and multiple system atrophy expand phenotypes of
      spinocerebellar ataxia type 2.
AB  - Spinocerebellar ataxia type 2 (SCA2) is a progressive neurodegenerative disorder,
      characterised by ataxic gait, slow saccades and peripheral neuropathy. Levodopa
      responsive parkinsonism could be a clinical phenotype of SCA2, especially those
      of Chinese origin. In addition to these motor symptoms, SCA2 has been associated
      with depression and cognitive dysfunction, with only rare reports of psychosis.
      The authors report the presence of severe psychosis, major depression and
      multiple system atrophy in affected subjects of a Taiwanese family with
      intermediate CAG repeats within the ATXN2 gene. The identification of this rare
      and distinctive SCA2 phenotype expands the current knowledge of the phenotypic
      variability of SCA2 and suggests that modifier genes could influence the clinical
      phenotype of SCA2.

PMID- 22605704
TI  - Corynebacterium jeikeium bacteraemia and pulmonary infiltrates in a patient with
      acute myelogenous leukaemia.
AB  - The authors used vancomycin (VCM) to treat Corynebacterium jeikeium bacteraemia
      and pulmonary infiltrates in a patient with acute myelogenous leukaemia.
      Pulmonary infiltrates are found in about one-third of patients with
      haematological pathologies accompanying C jeikeium bacteraemia. Although
      linezolid and daptomycin are antimicrobial alternatives for treating
      Corynebacterium infections, the authors believe that VCM is the best choice for
      immediate treatment success and to prevent pulmonary infiltrates from developing
      in the presence of bloodstream infection with Corynebacteria in patients with
      haematological malignancies.

PMID- 22605705
TI  - Recurrent pyogenic granuloma with satellitosis.
AB  - A 26-year-old woman was treated by curettage and cautery for a pyogenic granuloma
      on her left shoulder. This recurred 3 months later and was excised. After a
      further 5 months, she developed three vascular papules and one lobulated vascular
      lesion at the site. These ranged in size from 1-4 mm and the largest of these
      bled easily on minimal trauma. The authors treated the four vascular lesions with
      curettage and cautery and took a punch biopsy from an erythematous area in the
      scar. Histology was identical to the original lesion, confirming a diagnosis of
      recurrent pyogenic granuloma with satellitosis. One year later she had no
      evidence of recurrence of the lesions.

PMID- 22605706
TI  - Yellow nail syndrome associated with rheumatoid arthritis, thiol-compound therapy
      and early gastric cancer.

PMID- 22605707
TI  - Procedural sedation associated displacement of sharp oesophageal foreign body.
AB  - Oesophageal foreign body is a common clinical problem. The therapeutic
      intervention varies from endoscopic removal to observation for spontaneous
      passage of foreign body. The authors illustrate a case of sharp board pin
      ingestion by a child, which stayed impacted at C(7)-T(1) level for 8 h with
      indentation of tracheal mucosa. However, upon administration of midazolam and
      ketamine for procedural sedation, the pin spontaneously advanced to stomach when
      muscle relaxation had set in. A few oesophageal mucosal erosions were noted on
      the endoscopy. The foreign body could not be retrieved by the procedure and was
      spontaneously egested impacted in faeces. This case presents a distinctive hazard
      associated with procedural sedation for a foreign body in aero-digestive tract,
      where the associated muscle relaxation can lead to complications due to
      spontaneous movement of foreign body.

PMID- 22605708
TI  - Prosthodontic management of radiation induced xerostomic patient using flexible
      dentures.
AB  - Xerostomia causes discomfort for complete denture wearers as the tissues become
      dry and friable due to lack of lubricating properties of saliva. Common problems
      faced by such patients are glossitis, mucositis, angular chelitis, dysgeusia and
      difficulty in chewing and swallowing. This case report describes a new method in
      addressing such issues by using flexible complete denture construction in
      radiation induced xerostomic patient with minimal tissue damage during and after
      denture construction procedures.

PMID- 22605709
TI  - Teflon haemoptysis.
AB  - Teflon-coated pledgeted sutures can be used to reinforce the bronchial
      anastomosis site following a pulmonary resection in order to prevent
      bronchopleural fistula formation. The authors describe the case of a 42-year-old
      woman with recurrent haemoptysis secondary to the erosion of a pledgeted suture
      through the distal trachea. The pledgeted suture was used to reinforce a defect
      in the wall of the distal trachea after a right upper lobectomy for stage 2a
      squamous cell carcinoma. Surgically, a completion pneumonectomy with carinal
      reconstruction was thought necessary to treat the haemoptysis. Given her age and
      potential surgical morbidities, the decision was made to perform serial
      bronchoscopies with careful pruning and eventual removal of the pledget by using
      the cryoprobe and a flexible scissors. This resulted in the eventual removal of
      the suture. Follow-up bronchoscopy 4 weeks postremoval demonstrated no residual
      defect on the airway wall.

PMID- 22605710
TI  - Lambert-Eaton myasthenic syndrome and solitary cerebellar metastasis in a patient
      with occult small-cell lung cancer: a rare experience.
AB  - The authors describe a case of 60-year-old male patient presented with a 6 month
      history of progressive weakness of all the four limbs, ataxia, droopy eyelids and
      bulbar features. Further laboratory and electrodiagnostic studies confirmed the
      diagnosis of Lambert-Eaton myasthenic syndrome (LEMS). MRI of the brain showed a
      cerebellar tumour which, following surgery was revealed to be a metastatic small
      cell lung carcinoma. Paraneoplastic LEMS together with solitary cerebellar
      metastasis was diagnosed but no evidence of primary malignancy was detected. An
      extensive search for related malignancies failed to get any clue. The patient
      underwent a total surgical excision of tumour and the histopathology revealed a
      metastatic small cell carcinoma. This case highlights that rarely both
      paraneoplastic LEMS and cerebellar mass can precede the primary malignancy
      causing them.

PMID- 22605711
TI  - Di Sala syndrome.
AB  - Di Sala syndrome or fetal warfarin syndrome/fetal warfarin embryopathy is a rare
      condition as result of fetal exposure due to maternal ingestion of warfarin
      during pregnancy. The authors report here a male infant with this condition whose
      mother was suffering from rheumatic mitral valvular heart disease for which she
      underwent prosthetic mitral valvular replacement surgery and put on injectable
      long acting penicillin and oral low-molecular weight anticoagulant drug
      (warfarin) for life long. The patient presented with facial dysmorphism, pectus
      excavatum, stippled epiphyses dolichocephaly, brachydactyly, polydactyly short
      neck and growth retardation. Shortened fourth metacarpal bones were also noted in
      this case which was not yet reported in literatures, to the best of our
      knowledge.

PMID- 22605712
TI  - PET-CT aids in the diagnosis of a choroidal mass with retinal detachment in a
      patient with history of breast cancer and sarcoidosis.

PMID- 22605713
TI  - Ethylene glycol ingestion masked by concomitant ethanol intoxication.
AB  - An obtunded male with a history of alcohol abuse presented to the emergency
      department with metabolic acidosis, an osmolar gap and lactic acidosis. The
      patient was initially treated for alcohol intoxication due to an extremely high
      blood alcohol level. Following respiratory failure and intubation, a large volume
      of dark green liquid was removed via nasogastric suction; bedside fluorescence
      for ethylene glycol was negative. Twenty-four hours later, the patient's
      glomerular filtration rate decreased significantly, serum osmolality was 807, the
      osmolar gap was 407, complete metabolic panel showed pH of 6.8, sodium of 156
      mmol/l, potassium of 7.3 mmol/l, chloride of 116, CO(2) of 3.9 and anion gap of
      30.7. Blood lactic acid was >56 mmol/l. The patient received emergency
      haemodialysis. Four days after presentation, the patient began to respond to
      voice commands and was extubated. Currently, the patient still receives
      haemodialysis due to ongoing renal failure, but no long-term neurologic
      complications are evident.

PMID- 22605714
TI  - Pleomorphic xanthoastrocytoma with malignant transformation and multiple
      recurrences in an Iranian girl.
AB  - Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic tumour of the brain.
      Some PXAs are accompanied by anaplastic features and are difficult to manage
      because of frequent recurrences that lead to early death. Well-documented cases
      of malignant transformation in PXA and of anaplastic PXA are rare in the
      literature. The authors report a case of PXA with malignant transformation in the
      right temporo occipital lobe in a 13-year-old Iranian girl.

PMID- 22605715
TI  - Acute life-threatening methaemoglobinaemia following ingestion of chloroquine.
AB  - A 25 year old man was rushed to the emergency department when he was found
      unconscious in his room after taking two chloroquine tablets (600 mg base) for
      fever prescribed by local practitioner. On examination, the patient was
      unconscious and deep cyanosis was present on lips, tongue, oral cavity, nail beds
      and finger tips. Subsequent laboratory investigation revealed methaemoglobin
      level of 54%. Diagnosis of chloroquine-induced methaemoglobinaemia was made and
      methylene blue (1 mg/kg) was administered. The patient improved dramatically and
      was discharged following day.

PMID- 22605716
TI  - Sweet's syndrome in a patient with infective endocarditis: a rare clinical
      entity.
AB  - Sweet's syndrome, also known as acute febrile neutrophilic dermatosis, has been
      associated with malignancy, autoimmune disease and collagen vascular disease. The
      association of infective endocarditis and Sweet's syndrome is rare. The authors
      report a case of Sweet's syndrome in a patient with infective endocarditis.
      Infective endocarditis should be excluded in patients of rheumatic heart disease
      presenting with Sweet's syndrome. Alternatively, Sweet's syndrome should be
      considered as a differential diagnosis when a patient with infective endocarditis
      develops skin lesions.

PMID- 22605717
TI  - Osteonecrosis and femoro-acetabular impingement: sequelae of developmental
      dysplasia of the hip.
AB  - A 2-year-old girl with developmental dysplasia of the right hip underwent open
      reduction and capsulorrhaphy via the anterior approach with hip spica casting in
      an internally rotated position. During her 26 years of follow-up, she was found
      to have osteonecrosis and subsequently cam-type femoro-acetabular impingement at
      28 years of age. She was treated with surgical dislocation of the hip and
      osteochondroplasty to recreate the normal contour of the head and neck offset.

PMID- 22605718
TI  - Preventing mass violence.

PMID- 22605723
TI  - Biomedicine. A Texas wrangle over cancer research funds.

PMID- 22605724
TI  - Neuropathology. Blast injuries linked to neurodegeneration in veterans.

PMID- 22605725
TI  - AIDS research. FDA panel recommends anti-HIV drug for prevention.

PMID- 22605726
TI  - Newsmaker intervew: Stephen Pruitt. Coalition begins push for U.S. schools to
      adopt voluntary science standards. Interview by Jeffrey Mervis.

PMID- 22605727
TI  - Public health. China takes aim at rampant antibiotic resistance.

PMID- 22605728
TI  - Archaeology. Near Eastern archaeology works to dig out of a crisis.

PMID- 22605729
TI  - Infectious diseases. Can new chemistry make a malaria drug plentiful and cheap?

PMID- 22605730
TI  - Forced retirement goes out of style.

PMID- 22605731
TI  - Replication initiative: dangerous logic.

PMID- 22605732
TI  - Replication initiative: prioritize publication.

PMID- 22605733
TI  - Replication initiative: beware misinterpretation.

PMID- 22605734
TI  - The motherhood effect.

PMID- 22605736
TI  - Social psychology. Parochialism as a central challenge in counterinsurgency.

PMID- 22605737
TI  - Cell biology. An alternative route for nuclear mRNP export by membrane budding.

PMID- 22605738
TI  - Chemistry. Active site of an industrial catalyst.

PMID- 22605739
TI  - Chemistry. NMR tools for determining the structure of plutonium materials.

PMID- 22605740
TI  - Physics. Room for just one photon.

PMID- 22605741
TI  - Cell biology. Ancient sensor for ancient drug.

PMID- 22605742
TI  - Chemistry. Pinning down the water hexamer.

PMID- 22605743
TI  - Retrospective. Robert R. Sokal (1926-2012).

PMID- 22605746
TI  - Parsing terrorism.

PMID- 22605744
TI  - Human conflict. Human conflict: winning the peace. Introduction.

PMID- 22605747
TI  - Terrorism's long trail.

PMID- 22605748
TI  - In battle. Tribal roots in South Sudan.

PMID- 22605749
TI  - Roots of racism.

PMID- 22605750
TI  - In battle. Preening the troops.

PMID- 22605751
TI  - The battle over violence.

PMID- 22605752
TI  - In battle. Tweeting the London riots.

PMID- 22605753
TI  - Civilization's double-edged sword.

PMID- 22605754
TI  - The ultimate sacrifice.

PMID- 22605755
TI  - In battle. Fighting rituals.

PMID- 22605756
TI  - Gender and violence.

PMID- 22605757
TI  - In battle. From war to peace.

PMID- 22605758
TI  - Drone wars.

PMID- 22605759
TI  - Ancestral hierarchy and conflict.
AB  - Ancestral Pan, the shared predecessor of humans, bonobos, and chimpanzees, lived
      in social dominance hierarchies that created conflict through individual and
      coalitional competition. This ancestor had male and female mediators, but
      individuals often reconciled independently. An evolutionary trajectory is traced
      from this ancestor to extant hunter-gatherers, whose coalitional behavior results
      in suppressed dominance and competition, except in mate competition. A
      territorial ancestral Pan would not have engaged in intensive warfare if we
      consider bonobo behavior, but modern human foragers have the potential for full
      scale war. Although hunter-gatherers are able to resolve conflicts preemptively,
      they also use mechanisms, such as truces and peace pacts, to mitigate conflict
      when the costs become too high. Today, humans retain the genetic underpinnings of
      both conflict and conflict management; thus, we retain the potential for both war
      and peace.

PMID- 22605760
TI  - The group self.
AB  - Although people often tend to consider themselves and others as unique
      individuals, there are many situations in which they think, feel, and act
      primarily as group members. This can bring out the best in them, as when they are
      inspired to help fellow citizens in need, or the worst, as when they show
      hostility against others simply because they represent another religious or
      ethnic group. Understanding when and why the group self becomes more important
      than the individual self, and how this affects people's thoughts, feelings, and
      behaviors, can help to prevent and redirect unwelcome aspects of human behavior
      by addressing them at the appropriate level of self.

PMID- 22605761
TI  - Adapting to a multicultural future.
AB  - Humans have an evolved propensity to think categorically about social groups.
      This propensity is manifest in cognitive processes that have broad implications
      for public and political endorsement of multicultural policy. Drawing on these
      principles, we postulate a cognitive-evolutionary account of human adaptation to
      social diversity. This account explains broad social trends marking a resistance
      to multiculturalism, while providing an important reorienting call for scholars
      and policy-makers seeking intervention-based solutions to the problem of
      prejudice.

PMID- 22605762
TI  - Religious and sacred imperatives in human conflict.
AB  - Religion, in promoting outlandish beliefs and costly rituals, increases ingroup
      trust but also may increase mistrust and conflict with outgroups. Moralizing gods
      emerged over the last few millennia, enabling large-scale cooperation, and
      sociopolitical conquest even without war. Whether for cooperation or conflict,
      sacred values, like devotion to God or a collective cause, signal group identity
      and operate as moral imperatives that inspire nonrational exertions independent
      of likely outcomes. In conflict situations, otherwise mundane sociopolitical
      preferences may become sacred values, acquiring immunity to material incentives.
      Sacred values sustain intractable conflicts that defy "business-like"
      negotiation, but also provide surprising opportunities for resolution.

PMID- 22605763
TI  - Ethnicity and conflict: theory and facts.
AB  - Over the second half of the 20th century, conflicts within national boundaries
      became increasingly dominant. One-third of all countries experienced civil
      conflict. Many (if not most) such conflicts involved violence along ethnic lines.
      On the basis of recent theoretical and empirical research, we provide evidence
      that preexisting ethnic divisions do influence social conflict. Our analysis also
      points to particular channels of influence. Specifically, we show that two
      different measures of ethnic division--polarization and fractionalization-
      jointly influence conflict, the former more so when the winners enjoy a "public"
      prize (such as political power or religious hegemony), the latter more so when
      the prize is "private" (such as looted resources, government subsidies, or
      infrastructures). The available data appear to strongly support existing theories
      of intergroup conflict. Our argument also provides indirect evidence that ethnic
      conflicts are likely to be instrumental, rather than driven by primordial
      hatreds.

PMID- 22605764
TI  - Modeling armed conflicts.
AB  - Armed conflicts have been prevalent throughout history, in some cases having very
      great consequences. To win, one needs to understand the characteristics of an
      armed conflict and be prepared with resources and capabilities for responding to
      its specific challenges. An important tool for understanding these
      characteristics and challenges is a model--an abstraction of the field of
      conflict. Models have evolved through the years, addressing different conflict
      scenarios with varying techniques.

PMID- 22605765
TI  - Climate change and violent conflict.
AB  - Current debates over the relation between climate change and conflict originate
      in a lack of data, as well as the complexity of pathways connecting the two
      phenomena.

PMID- 22605766
TI  - Are we winning the war against posttraumatic stress disorder?
AB  - The most methodologically rigorous epidemiological study on American military
      personnel deployed to Iraq and Afghanistan found that 4.3% of troops developed
      posttraumatic stress disorder (PTSD). Among deployed combatants, 7.6% developed
      PTSD, whereas 1.4% of deployed noncombatants did so. The U.S. Department of
      Veterans Affairs has launched a program ensuring that all veterans with PTSD will
      receive evidence-based cognitive-behavioral therapy, and the Army has developed
      Battlemind postdeployment early interventions that reduce risk for the disorder.

PMID- 22605767
TI  - The antiquity of empathy.
AB  - The view of humans as violent war-prone apes is poorly supported by
      archaeological evidence and only partly supported by the behavior of our closest
      primate relatives, chimpanzees and bonobos. Whereas the first species is marked
      by xenophobia, the second is relatively peaceful and highly empathic in both
      behavior and brain organization. Animal empathy is best regarded as a
      multilayered phenomenon, built around motor mirroring and shared neural
      representations at basal levels, that develops into more advanced cognitive
      perspective-taking in large-brained species. As indicated by both observational
      and experimental studies on our closest relatives, empathy may be the main
      motivator of prosocial behavior.

PMID- 22605768
TI  - Warriors, levelers, and the role of conflict in human social evolution.
AB  - The origins of such varied features of contemporary life as the national state
      and the desire to uphold generous and civic social norms are to be found in a
      combination of conflict between groups and attenuation of both inequalities and
      conflicts within groups. In contrast to the adoption of a better tool or a more
      productive crop, which can be adopted by a single individual, a new institution
      works only if most people adopt it. This explains why collective action against
      those benefitting from the status quo at the expense of others, as well as
      conflict between groups governed by different norms and institutions, figures so
      prominently in our capacity to adapt to changing circumstances and to harness new
      knowledge for human benefit.

PMID- 22605769
TI  - Life without war.
AB  - An emerging evolutionary perspective suggests that nature and human nature are
      less "red in tooth and claw" than generally acknowledged by a competition-based
      view of the biological world. War is not always present in human societies. Peace
      systems, defined as groups of neighboring societies that do not make war on each
      other, exist on different continents. A comparison of three peace systems--the
      Upper Xingu River basin tribes of Brazil, the Iroquois Confederacy of upper New
      York State, and the European Union--highlight six features hypothesized to be
      important in the creation and maintenance of intersocietal peace: (i) an
      overarching social identity, (ii) interconnections among subgroups, (iii)
      interdependence, (iv) nonwarring values, (v) symbolism and ceremonies that
      reinforce peace, and (vi) superordinate institutions for conflict management. The
      existence of peace systems demonstrates that it is possible to create social
      systems free of war.

PMID- 22605771
TI  - Water-mediated proton hopping on an iron oxide surface.
AB  - The diffusion of hydrogen atoms across solid oxide surfaces is often assumed to
      be accelerated by the presence of water molecules. Here we present a high
      resolution, high-speed scanning tunneling microscopy (STM) study of the diffusion
      of H atoms on an FeO thin film. STM movies directly reveal a water-mediated
      hydrogen diffusion mechanism on the oxide surface at temperatures between 100 and
      300 kelvin. Density functional theory calculations and isotope-exchange
      experiments confirm the STM observations, and a proton-transfer mechanism that
      proceeds via an H(3)O(+)-like transition state is revealed. This mechanism
      differs from that observed previously for rutile TiO(2)(110), where water
      dissociation is a key step in proton diffusion.

PMID- 22605770
TI  - Evolutionary diversity of the mitochondrial calcium uniporter.
AB  - Calcium uptake into mitochondria occurs via a recently identified ion channel
      called the uniporter. Here, we characterize the phylogenomic distribution of the
      uniporter's membrane-spanning pore subunit (MCU) and regulatory partner (MICU1).
      Homologs of both components tend to co-occur in all major branches of eukaryotic
      life, but both have been lost along certain protozoan and fungal lineages.
      Several bacterial genomes also contain putative MCU homologs that may represent
      prokaryotic calcium channels. The analyses indicate that the uniporter may have
      been an early feature of mitochondria.

PMID- 22605772
TI  - Structures of cage, prism, and book isomers of water hexamer from broadband
      rotational spectroscopy.
AB  - Theory predicts the water hexamer to be the smallest water cluster with a three
      dimensional hydrogen-bonding network as its minimum energy structure. There are
      several possible low-energy isomers, and calculations with different methods and
      basis sets assign them different relative stabilities. Previous experimental work
      has provided evidence for the cage, book, and cyclic isomers, but no experiment
      has identified multiple coexisting structures. Here, we report that broadband
      rotational spectroscopy in a pulsed supersonic expansion unambiguously identifies
      all three isomers; we determined their oxygen framework structures by means of
      oxygen-18-substituted water (H(2)(18)O). Relative isomer populations at different
      expansion conditions establish that the cage isomer is the minimum energy
      structure. Rotational spectra consistent with predicted heptamer and nonamer
      structures have also been identified.

PMID- 22605773
TI  - Observation of 239Pu nuclear magnetic resonance.
AB  - In principle, the spin-1/2 plutonium-239 ((239)Pu) nucleus should be active in
      nuclear magnetic resonance spectroscopy. However, its signal has eluded detection
      for the past 50 years. Here, we report observation of a (239)Pu resonance from a
      solid sample of plutonium dioxide (PuO(2)) subjected to a wide scan of external
      magnetic field values (3 to 8 tesla) at a temperature of 4 kelvin. By mapping the
      external field dependence of the measured resonance frequency, we determined the
      nuclear gyromagnetic ratio (239)gamma(n)(PuO(2))/2pi to be 2.856 +/- 0.001
      megahertz per tesla (MHz/T). Assuming a free-ion value for the Pu(4+) hyperfine
      coupling constant, we estimated a bare (239)gamma(n)/2pi value of ~2.29 MHz/T,
      corresponding to a nuclear magnetic moment of MU(n) ~ 0.15MU(N) (where MU(N) is
      the nuclear magneton).

PMID- 22605774
TI  - Conspecific negative density dependence and forest diversity.
AB  - Conspecific negative density-dependent establishment, in which local abundance
      negatively affects establishment of conspecific seedlings through host-specific
      enemies, can influence species diversity of plant communities, but the generality
      of this process is not well understood. We tested the strength of density
      dependence using the United States Forest Service's Forest Inventory and Analysis
      database containing 151 species from more than 200,000 forest plots spanning
      4,000,000 square kilometers. We found that most species experienced conspecific
      negative density dependence (CNDD), but there was little effect of heterospecific
      density. Additionally, abundant species exhibited weaker CNDD than rarer species,
      and species-rich regions exhibited stronger CNDD than species-poor regions.
      Collectively, our results provide evidence that CNDD is a pervasive mechanism
      driving diversity across a gradient from boreal to subtropical forests.

PMID- 22605775
TI  - Randomized government safety inspections reduce worker injuries with no
      detectable job loss.
AB  - Controversy surrounds occupational health and safety regulators, with some
      observers claiming that workplace regulations damage firms' competitiveness and
      destroy jobs and others arguing that they make workplaces safer at little cost to
      employers and employees. We analyzed a natural field experiment to examine how
      workplace safety inspections affected injury rates and other outcomes. We
      compared 409 randomly inspected establishments in California with 409 matched
      control establishments that were eligible, but not chosen, for inspection.
      Compared with controls, randomly inspected employers experienced a 9.4% decline
      in injury rates (95% confidence interval = -0.177 to -0.021) and a 26% reduction
      in injury cost (95% confidence interval = -0.513 to -0.083). We find no evidence
      that these improvements came at the expense of employment, sales, credit ratings,
      or firm survival.

PMID- 22605776
TI  - Cost-benefit tradeoffs in engineered lac operons.
AB  - Cells must balance the cost and benefit of protein expression to optimize
      organismal fitness. The lac operon of the bacterium Escherichia coli has been a
      model for quantifying the physiological impact of costly protein production and
      for elucidating the resulting regulatory mechanisms. We report quantitative
      fitness measurements in 27 redesigned operons that suggested that protein
      production is not the primary origin of fitness costs. Instead, we discovered
      that the lac permease activity, which relates linearly to cost, is the major
      physiological burden to the cell. These findings explain control points in the
      lac operon that minimize the cost of lac permease activity, not protein
      expression. Characterizing similar relationships in other systems will be
      important to map the impact of cost/benefit tradeoffs on cell physiology and
      regulation.

PMID- 22605777
TI  - How hibernation factors RMF, HPF, and YfiA turn off protein synthesis.
AB  - Eubacteria inactivate their ribosomes as 100S dimers or 70S monomers upon entry
      into stationary phase. In Escherichia coli, 100S dimer formation is mediated by
      ribosome modulation factor (RMF) and hibernation promoting factor (HPF), or
      alternatively, the YfiA protein inactivates ribosomes as 70S monomers. Here, we
      present high-resolution crystal structures of the Thermus thermophilus 70S
      ribosome in complex with each of these stationary-phase factors. The binding site
      of RMF overlaps with that of the messenger RNA (mRNA) Shine-Dalgarno sequence,
      which prevents the interaction between the mRNA and the 16S ribosomal RNA. The
      nearly identical binding sites of HPF and YfiA overlap with those of the mRNA,
      transfer RNA, and initiation factors, which prevents translation initiation. The
      binding of RMF and HPF, but not YfiA, to the ribosome induces a conformational
      change of the 30S head domain that promotes 100S dimer formation.

PMID- 22605778
TI  - Aerobic microbial respiration in 86-million-year-old deep-sea red clay.
AB  - Microbial communities can subsist at depth in marine sediments without fresh
      supply of organic matter for millions of years. At threshold sedimentation rates
      of 1 millimeter per 1000 years, the low rates of microbial community metabolism
      in the North Pacific Gyre allow sediments to remain oxygenated tens of meters
      below the sea floor. We found that the oxygen respiration rates dropped from 10
      micromoles of O(2) liter(-1) year(-1) near the sediment-water interface to 0.001
      micromoles of O(2) liter(-1) year(-1) at 30-meter depth within 86 million-year
      old sediment. The cell-specific respiration rate decreased with depth but
      stabilized at around 10(-3) femtomoles of O(2) cell(-1) day(-1) 10 meters below
      the seafloor. This result indicated that the community size is controlled by the
      rate of carbon oxidation and thereby by the low available energy flux.

PMID- 22605779
TI  - Multiple spectral inputs improve motion discrimination in the Drosophila visual
      system.
AB  - Color and motion information are thought to be channeled through separate neural
      pathways, but it remains unclear whether and how these pathways interact to
      improve motion perception. In insects, such as Drosophila, it has long been
      believed that motion information is fed exclusively by one spectral class of
      photoreceptor, so-called R1 to R6 cells; whereas R7 and R8 photoreceptors, which
      exist in multiple spectral classes, subserve color vision. Here, we report that
      R7 and R8 also contribute to the motion pathway. By using electrophysiological,
      optical, and behavioral assays, we found that R7/R8 information converge with and
      shape the motion pathway output, explaining flies' broadly tuned optomotor
      behavior by its composite responses. Our results demonstrate that inputs from
      photoreceptors of different spectral sensitivities improve motion discrimination,
      increasing robustness of perception.

PMID- 22605780
TI  - Use of antidementia drugs in frontotemporal lobar degeneration.
AB  - INTRODUCTION: Clinical evidence indicates that acetylcholinesterase inhibitors
      (AChEIs) are not efficacious to treat frontotemporal lobar degeneration (FTLD).
      The British Association for Psychopharmacology recommends avoiding the use of
      AChEI and memantine in patients with FTLD. METHODS: Cross-sectional design using
      1092 cases with Alzheimer's disease (AD) and 64 cases with FTLD registered by the
      Registry of Dementias of Girona. Bivariate analyses were performed, and binary
      logistic regressions were used to detect variables associated with antidementia
      drugs consumption. RESULTS: The AChEIs were consumed by 57.6% and 42.2% of the
      patients with AD and FTLD, respectively. Memantine was used by 17.2% and 10.9% of
      patients with AD and FTLD, respectively. Binary logistic regressions yielded no
      associations with antidementia drugs consumption. CONCLUSIONS: There is a
      discrepancy regarding clinical practice and the recommendations based upon
      clinical evidence. The increased central nervous system drug use detected in FTLD
      requires multicentric studies aiming at finding the best means to treat these
      patients.

PMID- 22605782
TI  - Positive recognition program increases compliance with medication reconciliation
      by resident physicians in an outpatient clinic.
AB  - The purpose of this study was to determine if well-understood, positive
      reinforcement performance improvement models can successfully improve compliance
      by resident physicians with medication reconciliation in an outpatient clinical
      setting. During the preintervention phase, 36 anesthesiology residents who rotate
      in an outpatient pain clinic were instructed in the medication reconciliation
      process. During the postintervention phase, instruction was given, and then
      improvement was recognized publicly. Data on physician compliance were collected
      monthly. The authors performed a secondary analysis of the audit database, which
      contained 1733 patient charts. The data were divided into preintervention and
      postintervention phases for comparison. A 4-fold increase in compliance was
      found. When logistic regression was used to adjust for adaptation of resident
      physicians over time and year, the odds of reconciling were 82% higher
      postintervention. By the consistent application of this effective tool, the
      authors have demonstrated that sustained performance of a tedious but important
      task can be achieved.

PMID- 22605781
TI  - Commentary: electronic hand hygiene compliance interventions: a descriptive guide
      for the infection prevention team.

PMID- 22605783
TI  - Effect of automated, point-of-care electronic medical record screening for
      appropriate implantable device use in heart failure patients.
AB  - The authors evaluated the effects of an electronic health record (EHR)-based real
      time screening of outpatients for potential defibrillator therapy on practice
      metrics. Based on ejection fraction (EF) <= 35% and absence of a defibrillator,
      the physicians were prompted for an action: electrophysiology consultation, EF
      evaluation, or "not indicated." Although the number of patients screened remained
      stable at nearly 6000 per month, consultations and echocardiograms peaked early
      but returned to a low steady state by 10 months. The number of actual device
      implants did not increase appreciably as a result of this program. Implementation
      of a real-time EHR screening algorithm in a busy clinical practice is feasible
      and generally unobtrusive, without an effect on productivity. Its impact on
      adherence to guideline-based recommendation is not notable in this case. The
      number of resulting actionable items declines dramatically and plateaus by 10
      months, affording an opportunity to cycle, rather than add, other screening
      protocols.

PMID- 22605784
TI  - A psychometric evaluation of the core bereavement items.
AB  - Despite being a routinely administered assessment of grieving, few studies have
      empirically examined the psychometric properties of the Core Bereavement Items
      (CBI). The present study investigated the factor structure, internal reliability,
      and concurrent validity of the CBI in a large, diverse sample of bereaved young
      adults (N = 1,366). Exploratory and confirmatory factor analyses (conducted on
      randomly selected halves of the sample) supported a two-factor structure, with
      items tapping into grief-related Thoughts and Emotional Response to loss. These
      factors showed strong internal consistency and unique associations with
      demographic variables, circumstantial factors surrounding the loss, and a measure
      of prolonged/severe grief--highlighting the potential applicability of the
      identified factor structure.

PMID- 22605785
TI  - Development of abbreviated nine-item forms of the Raven's standard progressive
      matrices test.
AB  - The Raven's standard progressive matrices (RSPM) is a 60-item test for measuring
      abstract reasoning, considered a nonverbal estimate of fluid intelligence, and
      often included in clinical assessment batteries and research on patients with
      cognitive deficits. The goal was to develop and apply a predictive model approach
      to reduce the number of items necessary to yield a score equivalent to that
      derived from the full scale. The approach is based on a Poisson predictive model.
      A parsimonious subset of items that accurately predicts the total score was
      sought, as was a second nonoverlapping alternate form for repeated
      administrations. A split sample was used for model fitting and validation, with
      cross-validation to verify results. Using nine RSPM items as predictors,
      correlations of .9836 and .9782 were achieved for the reduced forms and .9063 and
      .8978 for the validation data. Thus, a 9-item subset of RSPM predicts the total
      score for the 60-item scale with good accuracy. A comparison of psychometric
      properties between 9-item forms, a published 30-item form, and the 60-item set is
      presented. The two 9-item forms provide a 75% administration time savings
      compared with the 30-item form, while achieving similar item- and test-level
      characteristics and equal correlations to 60-item based scores.

PMID- 22605786
TI  - Geographic variability of childhood food allergy in the United States.
AB  - OBJECTIVE: The aim of this study was to describe the distribution of childhood
      food allergy in the United States. METHODS: A randomized survey was administered
      electronically from June 2009 to February 2010 to adults in US households with at
      least 1 child younger than 18 years. Data were analyzed as weighted proportions
      to estimate prevalence and severity of food allergy by geographic location.
      Multiple logistic regression models were constructed to estimate the association
      between geographic location and food allergy. RESULTS: Data were analyzed for 38
      465 children. Increasing population density corresponded with increasing
      prevalence, from 6.2% in rural areas (95% confidence interval [CI] = 5.6-6.8) to
      9.8% in urban centers (95% CI = 8.6-11.0). Odds of food allergy were graded, with
      odds in urban versus rural areas highest (odds ratio [OR] = 1.7, 95% CI = 1.5
      2.0), followed by metropolitan versus rural areas (OR = 1.4, 95% CI = 1.2-1.5),
      and so on. Significance remained after adjusting for race/ethnicity, gender, age,
      household income, and latitude. CONCLUSIONS: An association between urban/rural
      status and food allergy prevalence was observed.

PMID- 22605787
TI  - Development of a set of mobile phone text messages designed for prevention of
      recurrent cardiovascular events.
AB  - BACKGROUND: Supporting lifestyle change is an effective way of preventing
      recurrent events in people with cardiovascular disease (CVD). However, there is a
      need to develop innovative strategies that increase access to programmes for
      individuals at high risk of CVD. This study aimed to develop a bank of text
      messages designed to provide advice, motivation, and support for decreasing
      cardiovascular risk. DESIGN: Iterative development process with mixed methods
      METHODS: An initial bank of 120 text messages was drafted based on behaviour
      change techniques, guidelines, and input from clinicians and public health
      experts. A questionnaire was then administered to participants (n = 53) for
      evaluation of message content, usefulness, and language. To test the process of
      delivery, a pilot study was conducted using a specifically designed computer
      programme that delivered messages to multiple mobile phones according to a pre
      specified schedule. Data were collected regarding message timing, delivery, and
      usefulness. RESULTS: In the qualitative questionnaire, 92% of participants found
      the messages easy to understand and 86% found the messages contained useful
      information. Positive feedback was also obtained from the pilot study. Based on
      these results, together with suggestions provided, several messages were reworded
      and an additional 44 were written. The need for semi-personalization was also
      identified and a random set of 103 individualized messages was created.
      CONCLUSIONS: A final bank of 137 mobile telephone text messages designed to
      support behaviour change and decrease cardiovascular risk have been developed
      through a multistep iterative process. This provides a scientific approach for
      future developers of health-related text messages.

PMID- 22605788
TI  - Optimal type 2 diabetes mellitus management: the randomised controlled OPTIMISE
      benchmarking study: baseline results from six European countries.
AB  - BACKGROUND: Micro- and macrovascular complications of type 2 diabetes have an
      adverse impact on survival, quality of life and healthcare costs. The OPTIMISE
      (OPtimal Type 2 dIabetes Management Including benchmarking and Standard
      trEatment) trial comparing physicians' individual performances with a peer group
      evaluates the hypothesis that benchmarking, using assessments of change in three
      critical quality indicators of vascular risk: glycated haemoglobin (HbA1c), low
      density lipoprotein-cholesterol (LDL-C) and systolic blood pressure (SBP), may
      improve quality of care in type 2 diabetes in the primary care setting. DESIGN:
      This was a randomised, controlled study of 3980 patients with type 2 diabetes.
      METHODS: Six European countries participated in the OPTIMISE study (NCT00681850).
      Quality of care was assessed by the percentage of patients achieving pre-set
      targets for the three critical quality indicators over 12 months. Physicians were
      randomly assigned to receive either benchmarked or non-benchmarked feedback. All
      physicians received feedback on six of their patients' modifiable outcome
      indicators (HbA1c, fasting glycaemia, total cholesterol, high-density lipoprotein
      cholesterol (HDL-C), LDL-C and triglycerides). Physicians in the benchmarking
      group additionally received information on levels of control achieved for the
      three critical quality indicators compared with colleagues. RESULTS: At baseline,
      the percentage of evaluable patients (N = 3980) achieving pre-set targets was
      51.2% (HbA1c; n = 2028/3964); 34.9% (LDL-C; n = 1350/3865); 27.3% (systolic blood
      pressure; n = 911/3337). CONCLUSIONS: OPTIMISE confirms that target achievement
      in the primary care setting is suboptimal for all three critical quality
      indicators. This represents an unmet but modifiable need to revisit the
      mechanisms and management of improving care in type 2 diabetes. OPTIMISE will
      help to assess whether benchmarking is a useful clinical tool for improving
      outcomes in type 2 diabetes.

PMID- 22605789
TI  - Rehabilitation.

PMID- 22605791
TI  - An eClinical trial system for cancer that integrates with clinical pathways and
      electronic medical records.
AB  - BACKGROUND: Various information technologies currently are used to improve the
      efficiency of clinical trials. However, electronic medical records (EMRs) are not
      yet linked to the electronic data capture (EDC) system. Therefore, the data must
      be extracted from medical records and transcribed to the EDC system. Clinical
      pathways are planned process patterns that are used in routine clinical practice
      and are easily applicable to the medical care and evaluation defined in a trial
      protocol. However, few clinical pathways are intended to increase the efficiency
      of clinical trials. PURPOSE: Our purpose is to describe the design and
      development of a new clinical trial process model that enables the primary use of
      EMRs in clinical trials by integrating clinical pathways and EMRs. METHODS: We
      designed a new clinical trial model that uses EMR data directly in clinical
      trials and developed a system to follow this model. We applied the system to an
      investigator-initiated clinical trial and examined whether all data were
      extracted correctly. At the protocol development stage, our model measures
      endpoints based on clinical pathways with the same diagnosis. Next, medical
      record descriptions and the format of the statistical data are defined. According
      to these observations, screens for entry of data, which are used both in clinical
      practice and for study, are prepared into EMRs with an EMR template, and screens
      are prepared for data checks on our EMR retrieval system (ERS). In an actual
      trial, patients are registered and randomly assigned to a protocol treatment. The
      protocol treatment is executed according to clinical pathways, and the data are
      recorded to EMRs using EMR templates. The data are checked by a local data
      manager using reports created by the ERS. After edit checks and corrections, the
      data are extracted by the ERS, archived in portable document format (PDF) with an
      electronic signature, and transferred in comma-separated values (CSV) format to a
      coordinating centre. At the coordinating centre, the data are checked,
      integrated, and made available for a statistical analysis. RESULTS: We verified
      that the data could be extracted correctly and found no unexpected problems.
      LIMITATION: To execute clinical trials in our system, the EMR template and
      efficient ERSs are required. Additionally, to execute multi-institutional
      clinical trials, it is necessary to create templates appropriate for EMRs at all
      participating sites and for the coordinating centre to validate local templates
      and procedures. CONCLUSION: We proposed and pilot tested a new eClinical trial
      model. Because our model is integrated with routine documentation of clinical
      practice and clinical trials, redundant data entries were avoided and the burden
      on the investigator was minimised. The reengineering of the clinical trial
      process would facilitate the establishment of evidence in the future.

PMID- 22605792
TI  - Measuring clinical decision making:  do key features problems measure higher
      level cognitive processes?
AB  - Reliable and objective assessment of clinical decision-making skills has been a
      long-standing goal in occupational testing in the allied health professions. With
      this goal in mind, the key features problem (KFP) format was developed which
      elicits targeted decisions about key features of clinical scenarios. To build on
      a small body of empirical evidence evaluating their efficacy, this study
      evaluates whether KFPs successfully assess higher order cognitive processes.
      Analysis of objective data (item length and difficulty, item performance, and
      response times) and subjective data (expert ratings of cognitive complexity)
      supported the proposition that KFPs tend to be more cognitively complex than
      conventional multiple-choice questions. Not only were they rated as more complex,
      but this complexity accounted for some of the increase in time spent responding
      to these items. Results support the use of KFPs in standardized assessments for
      measuring higher order cognitive processes such as clinical decision making.

PMID- 22605793
TI  - Enhancing job analysis surveys in the medical specialties with CMS data.
AB  - Job analysis surveys are a key component in validating certification examinations
      in the medical specialties. Few organizations, however, confirm the survey data
      gathering process using external data. This article demonstrates how an
      organization can use data from the Centers for Medicare & Medicaid Services (CMS)
      to supplement job analysis survey results using a real example from medical
      imaging. Organizations can also use CMS data longitudinally to predict which
      procedures are increasing and decreasing in frequency. This prediction can
      greatly assist with future comprehensive job analyses or smaller, more targeted
      updates between comprehensive job analyses.

PMID- 22605794
TI  - Renal cell carcinoma metastasis to the paranasal sinuses and orbit.
AB  - The authors report a rare case of renal cell carcinoma (RCC) metastasis to the
      paranasal sinuses. The authors review RCC and its potential for sinonasal
      metastasis and discuss the variable presentation and need for clinical suspicion
      for early diagnosis and treatment. A 74-year-old man presented with numbness of
      the left side of the face, reduced visual acuity and ptosis 12 years after
      nephrectomy for RCC. Imaging studies showed a lesion in the left pterygopalatine
      fossa and the histological features supported the diagnosis of metastatic RCC.
      RCC metastasis to the paranasal sinuses is very rare and can present with various
      symptoms depending on the affected organ. These symptoms occasionally are the
      initial manifestation of renal RCC and it is very important to recognise them so
      that the patient receives the appropriate therapy to improve survival.

PMID- 22605795
TI  - Benign metastasising leiomyoma: a progressive disease despite chemical and
      surgical castration.
AB  - Benign metastasising leiomyoma (BML) is a rare entity characterised by uterine
      leiomyoma that, later on, develops slow-growing metastasis mainly to the lung. In
      general, these lung metastases are incidentally discovered, but sometimes can
      become symptomatic with dyspnoea, cough and chest pain. The expression of
      oestrogen and progesterone receptors by these tumours supports the idea that they
      respond to hormone therapy (chemical, with oestrogen receptor modulators,
      aromatase inhibitors or luteinising hormone releasing hormone analogues and
      surgical, with bilateral adnexectomy). The authors present a case report of BML
      with two peculiarities: a less common pattern of metastisation (soft tissue), in
      addition to lung; and disease progression despite treatment with chemical and
      surgical castration.

PMID- 22605796
TI  - An older patient with bilateral non-traumatic haemothoraces.
AB  - This is the case of a patient who presented with bilateral spontaneous
      haemothoraces. Video-assisted thoracoscopic surgery was performed bilaterally to
      evacuate the haemothorax and perform biopsies. The patient was diagnosed with
      bilateral malignant epithelioid hemangioendothelioma of the pleura and
      pericardium. To our knowledge, this is the first description of bilateral
      malignant epithelioid hemangioendothelioma of the pleura presenting with
      haemothoraces and without obvious pulmonary involvement. Malignant epithelioid
      hemangioendothelioma is a rare form of malignancy that can present with
      unilateral or bilateral haemothoraces.

PMID- 22605797
TI  - An unusual haemoperitoneum--secondary abdominal pregnancy.
AB  - A 36-year-old amenorrhoeic patient presented with vague abdominal discomfort, and
      haemodynamic instability, a large haemoperitoneum was identified on transvaginal
      ultrasound. Ruptured tubal ectopic pregnancy was suspected. At laparotomy
      ruptured primary tubal ectopic pregnancy was identified, with 12-14 week
      secondary abdominal pregnancy implanted onto the omentum, confirmed by
      histopathology. Salpingo-oophrectomy with peritoneal washout was performed, and
      three units blood transfusion was required. The patient had an uneventful
      recovery to health.

PMID- 22605798
TI  - Primary amyloidoma of chest wall--a rare condition.
AB  - Organ specific amyloidosis has been shown to be confined to various organs like
      liver, lung, spleen, urinary bladder and gastro-intestinal tract, but amyloidoma
      or tumoural amyloidosis of chest wall with no evidence of systemic amyloidosis is
      an extremely rare presentation and only two cases have been reported till now.
      The authors report a case of chest wall amyloidoma with review of literature.

PMID- 22605799
TI  - Falling up the stairs: the equivalent of 'bashing it with a bible' for an ACL
      ganglion cyst of the knee.
AB  - Intra-articular anterior cruciate ligament (ACL) cysts are rare, the pathogenesis
      remains unknown, with trauma often implicated. Often asymptomatic, incidental MRI
      findings, 11% produce symptoms such as pain, locking or instability. Treatment of
      intra-articular ganglia differs from the traditional 'bash it with a bible'
      mantra for ganglia elsewhere with surgical debridement generally indicated for
      symptomatic cases. This case report describes a 43-year-old male car mechanic who
      presented with a symptomatic ACL cyst diagnosed on MRI. While waiting for surgery
      the patient fell up his stairs at home, causing forced hyperflexion of his knee.
      After an initial sharp pain, within 24 h the patient experienced complete
      resolution of symptoms. Postfall MRI showed no evidence of the initial lesion,
      leading to our conclusion that for this patient, a fall up the stairs was the
      equivalent of 'bashing it with a bible' for an ACL ganglion cyst of the knee.

PMID- 22605800
TI  - 'Ping pong' fracture in a term infant.

PMID- 22605801
TI  - Eosinophilic acute appendicitis caused by Strongyloides stercoralis and
      Enterobius vermicularis in an HIV-positive patient.
AB  - A 29 year old female HIV-positive patient presented in emergency with acute right
      lower quadrant abdominal pain, fever, tenderness and positive Blumberg sign.
      Laboratorial tests revealed eosinophilia, anaemia and leukocytosis. She underwent
      exploratory laparotomy followed by appendectomy. The pathological analysis of the
      appendix revealed acute appendicitis, accentuated eosinophilia and infestation by
      Strongyloides stercoralis and Enterobius vermicularis. She did well after surgery
      and adequate treatment. To the authors' knowledge, this is the first case of
      eosinophilic acute appendicitis caused by these two parasitic worms reported in
      the medical literature.

PMID- 22605802
TI  - T cell acute lymphoblastic leukaemia presenting with sudden onset right
      oculomotor nerve palsy with normal neuroradiography and cerebrospinal fluid
      studies.
AB  - Leptomeningeal disease presenting with neurological dysfunction is not uncommon
      in leukaemia. However, it is often accompanied by abnormalities in cerebrospinal
      fluid (CSF) studies and/or neuroradiography. Here, the authors describe a case of
      a young patient presenting with sudden onset right oculomotor nerve palsy with
      normal neuroradiography and CSF studies, who was subsequently diagnosed to have T
      cell acute lymphoblastic leukaemia (T-ALL). This case highlights that
      neurological manifestations can be the initial presenting feature of T-ALL and
      can occur suddenly despite normal neuroradiography and initial CSF studies.

PMID- 22605803
TI  - Multidrug-resistant tuberculosis that required 2 years for diagnosis.
AB  - Isoniazid (H) or rifampicin (R) mono-resistant disease can be treated easily and
      effectively with first-line drugs, while combined H and R resistance (ie,
      multidrug-resistant tuberculosis (MDRTB)) requires treatment with at least four
      agents, including a quinolone and an injectable agent. Drug-resistant
      Mycobacterium tuberculosis strains are reported to be extremely difficult to
      cultivate invitro. The authors report a case of MDRTB that required 2 years for
      diagnosis, and was detected only in sputum culture on solid medium. Physicians
      should consider MDRTB if TB is suspected but pathogens are not detected.

PMID- 22605804
TI  - Towards creating a superstimulus to normalise glucose metabolism in the
      prediabetic: a case-study in the feast-famine and activity-rest cycle.
AB  - We live in a time of plenty. During evolution, periods of hunger and
      simultaneously high activity levels would combine giving a stimulus which is
      absent from modern lifestyles. This is potentially connected with abnormal
      glucose metabolism. It was hypothesised that simultaneous fasting and aggressive
      aerobic neuromuscular electrical stimulation (NMES) exercise, until metabolic
      exhaustion, may be an acceptable modern equivalent. A healthy subject fasted for
      44 h (water allowed) during which he undertook three aerobic NMES sessions at
      >50%VO(2max); heart rate >160 bpm. Metabolic gas analysis of a comparable session
      in the non-fasting state showed 100% carbohydrate substrate utilisation. With
      fasting the NMES exercise consumed mostly fat-up to 100% fat utilisation at 42 h.
      This clear shift away from using carbohydrate as a substrate and hypoglycaemia
      may indicate that carbohydrate stores are nearly depleted. The authors postulate
      that this may constitute a metabolic super stimulus mimicking the famine-activity
      periods of our ancestors.

PMID- 22605805
TI  - Flash pulmonary oedema: a rare but serious side effect of quinine sulphate.
AB  - A 54-year-old woman with a background of psoriatic arthritis but no cardiac
      history was admitted with acute pulmonary oedema (November 2007) which required
      invasive ventilation and inotropic support. Investigations including ECG,
      transthoracic and transoesophageal echocardiography, coronary angiography, renal
      ultrasound and renal magnetic resonance angiography, cardiac MRI and urinary
      catecholamines were normal. Due to the lack of precipitant, the authors assumed
      this was due to nabumetone (a non-steroidal anti-inflammatory drug (NSAID)) which
      was stopped. A second similar episode (August 2008) was temporally associated
      with a depo steroid injection, although no NSAID was given. Steroids have
      subsequently been restricted. However, she was admitted again with pulmonary
      oedema (April 2010) despite not taking NSAIDs or steroids. At that stage, she
      advised us that she had been taking quinine sulphate on an as required basis and
      had taken oral doses before each episode of pulmonary oedema which the authors
      now believe to have been the precipitant.

PMID- 22605806
TI  - Saccharomyces boulardii fungemia caused by treatment with a probioticum.
AB  - Saccharomyces cerevisiae, known as baker's yeast, is normally considered a non
      pathogenic yeast. A genetically very similar subtype, S boulardii, is used in a
      probioticum (Sacchaflor) to prevent antibiotic-associated diarrhoea and in the
      treatment of recurrent Clostridium difficile associated diarrhoea. The authors
      present a case report of a 79-year-old woman with rheumatoid arthritis, who after
      a bowel resection developed S boulardii fungemia. Her postoperative course was
      complicated by nutritional problems, anaemia and several nosocomial infections
      including recurrent C difficile associated diarrhoea. The diarrhoea was treated
      with metronidazole, vancomycin and Sacchaflor. After 13 days of treatment, the
      patient developed fungemia with S boulardii. Treatment with Sacchaflor was
      immediately discontinued and the patient was successfully treated with
      amphotericin B. Fungemia is a rare, but a serious complication to treatment with
      probiotics. Accordingly, the authors find it important to remind the clinicians
      of this risk when prescribing probiotics especially to immunocompromised
      patients.

PMID- 22605807
TI  - Mediastinal ganglioneuroma mimicking a bronchogenic cyst.

PMID- 22605808
TI  - Tuberculosis of sacrum mimicking as malignancy.
AB  - Tuberculosis has always been a menace for both clinicians and radiologists due to
      its often non-specific and protean manifestations. Isolated tubercular
      involvement of sacrum is very rare. The authors present the case of a 38-year-old
      man with history of low-grade fever, pain and swelling in the sacral region.
      Skiagram revealed an osteolytic lesion of sacrum leading to the provisional
      diagnosis of chordoma and osteoclastoma. However, MRI was suggestive of a chronic
      infective condition like tuberculosis and fine needle aspiration cytology was
      positive for acid-fast bacilli and revealed epitheloid granulomas with caseous
      necrosis. Culture was positive for Mycobacterium tuberculosis. Antitubercular
      therapy was commenced and surgical decompression of cold abscess was done and
      with good clinical response. This case highlights the importance of remaining
      cognisant of the manifestations and the importance of considering tuberculosis as
      a diagnosis at unusual sites of involvement.

PMID- 22605809
TI  - Antifreeze on a freezing morning: ethylene glycol poisoning in a 2-year-old.
AB  - This case report describes the presentation and management of a 2-year-old child
      who ingested a potentially fatal amount of ethylene glycol (EG). There are few
      published cases worldwide of EG poisoning in children managed with fomepizole.
      All cases described in the literature were managed in a paediatric intensive care
      unit. In this case, the child presented irritable, pale and confused with high
      anion gap metabolic acidosis. As there were no paediatric intensive care beds
      available in the region, the child was successfully managed in a high dependency
      area in our district general hospital. The child fully recovered and was
      discharged home in 7 days. The authors believe that multi-disciplinary team
      management and the use of fomepizole contributed to the positive outcome and this
      case raised many useful learning points.

PMID- 22605810
TI  - Sweet's syndrome in a patient with Wegener's granulomatosis and ESRD.
AB  - A female patient in her late 60s with end stage renal disease secondary to
      Wegener's granulomatosis presented with a 2-day history of fever, nausea,
      somnolence and purple coloured exudative plaques on her forehead and index
      finger. Herpes zoster was the initial diagnosis and acyclovir was prescribed.
      Twenty-four hours later, her level of consciousness (LOC) had declined to a
      Glascow coma scale of 10/15 and she started exhibiting myoclonic jerks. The
      lesions progressed to both sides of the face and acyclovir was discontinued as it
      was felt to be contributing to the myoclonic jerks. CT scan of the brain and
      lumbar puncture revealed no abnormalities to explain diminished LOC. Septic
      screen was negative, and an EEG showed no ictal activity. Skin biopsy revealed
      neutrophilic dermal infiltrates, leading to the diagnosis of Sweet's syndrome and
      prednisone (1 mg/kg) was initiated. The patient's condition improved over 12 h
      and she was discharged 5 days later. She died 6 weeks later from her cardiac
      disease.

PMID- 22605811
TI  - A 66-year-old male with lower abdominal lump: an unusual presentation of an
      uncommon abdominal pathology.
AB  - A 66-year-old Caucasian male was admitted following symptoms of intermittent
      umbilical pain aggravated after meals and associated with vomiting of contents.
      Physical examination revealed a tender, partially reducible swelling suspicious
      of complicated umbilical hernia. Abdominal x-ray revealed dilated small bowel
      loops which appeared consistent with clinical diagnosis. He underwent a
      laparotomy subsequently which revealed a small defect in the linea alba with
      viable small bowel and two firm mesenteric masses encroaching the lumen
      approximately two feet from the ileocaecal junction. The histology of the excised
      bowel and masses revealed that the tumour composed of bland spindle cells with
      slender to plump nuclei and eosinophilic cytoplasm. Mesenteric fibromatosis are
      the most common primary tumours of the mesentery and constitute about 3.5% of all
      fibrous tissue tumours. Intra-abdominal desmoids are very rare and benign tumours
      but are very aggressive and should be considered in the differential diagnosis of
      acute abdominal pain.

PMID- 22605812
TI  - MR spectroscopy in tuberculoma of brain.

PMID- 22605813
TI  - Pneumomediastinum in a snorkelling diver.
AB  - Pneumomediastinum is an uncommon disorder seen in shallow water divers. The
      authors present the case of a 25-year-old who sustained a pneumomediastinum while
      snorkelling; his presentation, investigation results, treatment and response.

PMID- 22605814
TI  - Intracardiac bronchogenic cyst in a 2-year-old Nigerian boy.
AB  - Primary cardiac tumours are rare in the paediatric age group. Bronchogenic cysts,
      although relatively rare, represent the most common cystic lesion of the
      mediastinum. Intracardiac bronchogenic cysts however, are extremely rare. The
      authors are unaware of any case previously reported in a Nigerian child and hence
      report the case of a 2-year-old boy for its rarity and interest. The boy was
      referred for evaluation of a cardiac murmur. Clinical, radiological and
      electrographic findings were suggestive of mild pulmonary stenosis or an atrial
      septal defect (ASD). 2-dimensional echocardiography however, revealed in addition
      to a small ASD, an intracardiac mass attached to the tricuspid valve. The mass
      was surgically removed and found on histology to be a bronchogenic cyst. Our
      experience highlights the importance of echocardiography in the evaluation of
      asymptomatic patients with cardiac murmurs, in whom a rare lesion might have
      otherwise been missed.

PMID- 22605815
TI  - Thrombosed prosthetic mitral valve.

PMID- 22605816
TI  - Massive pulmonary thromboembolism after intravenous stroke thrombolysis.
AB  - The authors present a 76-year-old female with high blood pressure and
      hypercholesterolaemia as cerebrovascular risk factors, who received intravenous
      thrombolysis for an ischaemic stroke with a progressive neurological improvement.
      She was asymptomatic at 48 h and she was transferred to the neurology department
      where antithrombotic treatment was initiated. She began to sit the following day
      when she suffered a massive pulmonary embolism (PE). Cardiological study showed
      patent foramen oval persistence and the presence of an atrial septa aneurysm, and
      paroxysmal atrial fibrillation. The delay of the onset of the antithrombotic
      treatment could have been determinant for the massive PE. Thromboembolic
      complications may be seen after intravenous thrombolysis for ischaemic stroke. An
      accurate treatment is needed in order to avoid potentially threatening
      complications such as massive PE.

PMID- 22605817
TI  - Subarachnoid haemorrhage mimicking acute myocardial infarction.

PMID- 22605818
TI  - The role of breast MRI in the investigation of anti-Yo positive paraneoplastic
      cerebellar degeneration.
AB  - Paraneoplastic neurological syndromes are a group of rare and heterogeneous
      disorders complicating cancer through immune-mediated mechanisms. They typically
      arise before the diagnosis of malignancy, thus constituting its first clinical
      manifestation. A thorough search for the underlying tumour is necessary, as
      adequate tumour management is essential for both neurological prognosis and
      overall survival. The authors present the case of a 43 year-old woman who
      presented with a subacute cerebellar syndrome associated with the paraneoplastic
      anti-Yo antibody. Although paraneoplastic aetiology was immediately suspected,
      the diagnosis of the underlying tumour was not straightforward, as is often the
      case. This case report highlights the importance of directing tumour search for
      the most probable anatomic locations, according to patient demographics and risk
      factors as well as the type of onconeural antibodies present, and also the need
      to use the most sensitive diagnostic modalities appropriate for each target
      organ.

PMID- 22605819
TI  - Atypical central serous retinopathy in a patient with latent tuberculosis.
AB  - A 32-year-old Afro-Caribbean male presented with a 4 month history of blurred
      vision and distortion in his right eye. Fundus examination showed multiple
      pigment epithelial detachments which progressed over 2 months of observation to a
      large serous detachment of the macula. Fundus fluorescein angiography (FFA)
      showed multi-focal hyperfluorescence in the early phase which increased in the
      later stages. A diagnosis of multi-focal central serous retinopathy (CSR) was
      made. Due to the size of CSR and atypical findings on FFA further investigations
      including a T-spot test were performed. The T-spot test was reported as strongly
      positive and following discussion with the respiratory physicians he was started
      on empiric antituberculous therapy. Over the next 6 weeks, the patient had a
      significant visual improvement to 6/9 with resolution of the serous detachment.

PMID- 22605820
TI  - Early appearance of osteonecrosis of the jaw after zoledronic acid in a patient
      with a long history of taking oral bisphosphonates.
AB  - Osteonecrosis of the jaw (ONJ) is a serious side effect in patients receiving
      intravenous nitrogen-containing bisphosphonates (B). It has also been reported to
      occur due to oral administration of B. Most cases will appear after receiving B
      for more than 1 year. The authors report a case of a 67-year-old woman with
      osteoporosis who had received oral alendronate sodium for 2 years and stopped the
      treatment due to dyspepsia. 18 months later she was diagnosed with breast cancer
      and bone metastases. She started a treatment based on aromatase inhibitors and
      zoledronic acid (Z). She developed ONJ soon after the third administration. She
      was treated with antibiotics, anti-inflammatories and a chlorexidine colutory.
      She recovered 3 months later. ONJ secondary to Z may occur also earlier than it
      was thought in patients with a history of taking oral B.

PMID- 22605821
TI  - Spontaneous presacral haematoma mimicking rectal malignancy--an unusual
      consequence of anticoagulation.
AB  - An 81-year-old man on warfarin was admitted to hospital after 3 days of
      constipation, straining and mild rectal bleeding. A large, boggy mass was felt
      posteriorly on direct rectal examination. Investigations revealed a normocytic
      anaemia and a supratherapeutic international normalised ratio (INR). Fearing a
      late presentation of malignancy, an urgent CT of abdomen and pelvis was arranged
      which showed a homogeneous mass arising between the sacrum and the rectum. Given
      the anaemia in the presence of anticoagulation, and subsequent widespread
      perineal and scrotal ecchymosis, the patient was diagnosed with atraumatic
      presacral haematoma. Following resuscitation, the patient was managed non
      operatively and was discharged several days later following stabilisation of the
      haemoglobin and INR. At 3 months, he had complete clinical and radiological
      resolution of this haematoma.

PMID- 22605822
TI  - Use of decompression tubes in the management of excessively large odontogenic
      keratocyst.
AB  - Odontogenic keratocyst (OKC) is a unique cyst because of its locally aggressive
      behaviour, high recurrence rate and characteristic histological appearance. A
      radical surgical approach is commonly advocated with morbid and disfiguring
      results. This approach also presents several reconstructive obstacles especially
      in anterior mandible. In this case report the authors present a 25-year-old male
      patient with a large OKC and treatment with decompression followed by
      enucleation, and chemical cauterisation. This approach though demanding prolonged
      treatment time and postoperative follow-up decreases the morbidity to a great
      extent in a young individual. At the same time, it allows an opportunity for the
      maxillofacial surgeon to preserve the natural dentition, maintain function and
      safeguard cosmesis. In our case, the authors effectively achieved all the
      aforementioned objectives. At the same time a radical option of treatment is
      still left in the armoury if required at a later date.

PMID- 22605823
TI  - Right heart free-floating thrombus after leg injury.

PMID- 22605824
TI  - Resistance to thyroid hormone--an incidental finding.
AB  - A 16-year-old female with mild hirsutism was noted to have a small, smooth, non
      tender goitre. A resting peripheral tremor, but no other symptoms or signs of
      thyroid dysfunction were present. Her only medication was the contraceptive pill.
      There was no family history of thyroid disease. Investigation showed elevated
      free thyroxine (28 pmol/l) and total triiodothyronine (3.4 nmol/l) with non
      suppressed thyroid stimulating hormone (1.4 mU/l). Radioiodine uptake scan of the
      thyroid showed bilateral increased tracer uptake, suggestive of Graves' disease,
      however thyroid peroxidase and antithyroid stimulating hormone (TSH) receptor
      antibody testing was negative and sex hormone binding globulin concentration was
      normal. Laboratory analyses excluded assay artefact or abnormal circulating
      thyroid hormone binding proteins. Genetic analysis identified a thyroid hormone
      receptor gene mutation (T277I), making a diagnosis of resistance to thyroid
      hormone (RTH). RTH is a disorder characterised by elevated thyroid hormones,
      failure to suppress pituitary TSH secretion and variable refractoriness to
      hormone action in peripheral tissues.

PMID- 22605825
TI  - A rare entity of primary extranodal diffuse large B cell lymphoma of the lower
      limb calf in an HIV-infected young adult on highly active antiretroviral therapy.
AB  - Primary cutaneous and skeletal muscle lymphomas are particularly rare phenomena
      in HIV sero-positive patients. The authors report a case of primary extranodal
      malignant diffuse large B cell lymphoma of the left gastrocnemius in a 21-year
      old young adult who presented to the Infectious Diseases Institute, Kampala,
      Uganda having been on antiretroviral therapy for 2 years. The patient is still
      undergoing chemotherapy.

PMID- 22605826
TI  - Paraspinal sinuses? Do remember renal tuberculosis.
AB  - Approximately 4%-8% of patients with pulmonary tuberculosis develop clinically
      significant genitourinary infection. In the case being reported, a 30-year-old
      female, admitted with right-sided back swelling, local pain and low-grade fever.
      The swelling gradually increased in size over a period of 6 months and had burst
      spontaneously forming a pus discharging with associated localised pain and fever
      bringing the patient to the hospital. X-ray lumbar spine, chest and kidney ureter
      bladder showed no abnormalities. Ultrasound findings were suggestive of
      pyonephrosis with a posterior paraspinal abscess with a sinus tract within the
      posterior paraspinal region. CT findings were more conclusive in suggesting the
      sinus tract origin. Finding of tuberculous kidney and upper ureteric stricture
      with sinus tract opening in the posterior paraspinal region was made on CT. Right
      nephrectomy was done. Histopathologically proved it to be tuberculous kidney.

PMID- 22605828
TI  - Photo quiz: A 45-year-old male with rash, fever, and diarrhea.

PMID- 22605827
TI  - A 3-month-old baby with H1N1 and Guillain-Barre syndrome.
AB  - Majority of children with pandemic influenza A (H1N1)pdm09 experience mild
      illness with full recovery without treatment. A previously healthy two and a half
      month-old girl was admitted to our paediatric intensive care unit because of
      severe respiratory failure with A (H1N1)pdm09 infection. Despite initial clinical
      improvement all attempts to extubate to non-invasive ventilation were
      unsuccessful and 2 to 3 weeks after symptom onset she started periods of
      cardiovascular instability and a progressive neurological deterioration with
      distal symmetrical progressive motor weakness and areflexia. All investigations
      were normal except elevated liver enzymes and cerebrospinal fluid examination
      that revealed elevated protein without pleocytosis. A possible diagnosis of
      Guillain-Barre syndrome (GBS) was considered and electromyogram was compatible
      with axonal form of GBS. To our knowledge this is the youngest case of GBS
      acquired postnatally and the first in children associated with H1N1 virus.

PMID- 22605830
TI  - Electrocardiographic changes in an athlete before and after detraining.

PMID- 22605831
TI  - Autoimmune pernicious anaemia as a cause of collapse, heart failure and marked
      panyctopaenia in a young patient.
AB  - A 35-year-old woman with a history of vitiligo, hypothyroidism and amenorrhoea
      presented with collapse and clinical features of cardiac failure. Laboratory
      investigations revealed pancytopaenia, the cause of which was found to be vitamin
      B12 deficiency due to pernicious anaemia. Treatment with intramuscular
      hydroxycobalamin was commenced and the patient improved steadily with concomitant
      improvement in her haematological indices. Clinical features of pernicious
      anaemia which can include marked pancytopaenia, diagnostic approach, associated
      conditions and approach to treatment are discussed. The importance of
      surveillance for gastrointestinal malignancy is emphasised.

PMID- 22605832
TI  - Acute scoliosis in a 3-year-old boy.
AB  - The case describes the presentation of a fit and well 3-year-old boy to the
      emergency department of a district general hospital after he developed an acute
      scoliosis overnight. There was no history of trauma, his observations were normal
      and he had non-specific symptoms of lethargy and reduced appetite, but no fevers
      or respiratory distress. Bloods showed raised inflammatory markers and he was
      referred to orthopaedics as a septic disc as there was some spinal tenderness. An
      urgent MRI was considered initially but on further examination there was some
      reduced air entry on the left lung base which a chest radiograph confirmed as a
      left-sided pneumonia. A diagnosis of pneumonia and secondary functional scoliosis
      was made. The child was admitted under paediatrics and made a full recovery on
      antibiotics. At 8 weeks follow-up there was resolution of scoliosis clinically
      and radiologically.

PMID- 22605833
TI  - Cervical lymphadenopathy: metastasis of papillary carcinoma or ectopic thyroid
      tissue?
AB  - Papillary thyroid carcinoma frequently metastasises to the regional neck lymph
      nodes. However, cervical lymph node metastases as sole manifestation of occult
      papillary thyroid carcinoma are observed rarely. The authors report the case of a
      52-year-old man presenting for slowly enlarging neck region and shortness of
      breath, with an insidious history for 15 years. Thyroid imaging showed a goitre
      predominantly of the right lobe, but histopathological finding revealed a multi
      centric thyroid papillary carcinoma with lymph node metastasis.

PMID- 22605834
TI  - Complicated septic cervical and lumbar discitis.
AB  - A 69-year-old lady presented with back pain for 5 days associated with spiking
      temperatures, lower limb weakness and urinary retention. Urgent MRI showed
      discitis at the disc between cervical vertebra seven (C7), thoracic vertebra one
      (T1) and lumbar vertebra three and four (L3-4), associated dural inflammation,
      stenosis of the cervical spinal canal and cervical cord oedema at the level of
      C3. No definite epidural abscess was seen. She was transferred to the spinal unit
      for observation. Following transfer she rapidly developed respiratory compromise
      and required emergency spinal decompression later that day.

PMID- 22605835
TI  - Complication of etanercept treatment for rheumatoid arthritis--purulent
      pericarditis caused by a commensal organism.
AB  - The patient presented with increasing fatigue and dyspnoea. The patient had
      medical history of rheumatoid arthritis for which she had been taking
      methotrexate for the past 15 years and etanercept for the past 6 years. Initial
      diagnosis was cardiac failure but further investigation by echocardiogram
      revealed a large pericardial effusion. Empirical piperacillin-tazobactam was
      started due to moderately raised inflammatory markers. Four hundred millilitre of
      frank pus was aspirated from the pericardial sac and antimicrobial treatment was
      changed to meropenem. Gram positive cocci were seen in the initial Gram stain,
      but conventional cultures remained negative. However, 16S ribosomal RNA gene
      sequencing of the pus sample detected the presence of Parvimonas micra genome.
      Reaccumulation of the effusion required further drainage where again P micra was
      detected by 16S ribosomal RNA gene sequencing. Two weeks of meropenem was
      completed followed by treatment with benzylpenicillin and metronidazole.

PMID- 22605836
TI  - Life-threatening hyperkalemia--an overlooked acute kidney injury with a serum
      creatinine rise in the 'normal' range.
AB  - A 76-year-old woman (51 kg, 158 cm, body mass index 20.5) was admitted to the
      hospital because of an acute kidney injury with hyperkalemia. On admission, she
      reported progredient muscle weakness of all limbs for several days. Serum
      potassium level was dramatically elevated and ECG showed QRS with a 'sine-wave'
      pattern and haemodialysis was started. 45 days ago, Hartmann's operation was done
      because of stenosing sigmoid diverticulitis. At this time, the serum creatinine
      was 0.4 mg/dl ('normal' 0.5-1.2). Thereafter, she got severe 'high output
      ileostoma' with severe intestinal fluid losses and treatment with potassium
      supplementation and spironolactone was started by the surgeons. She was
      discharged with elevated serum potassium levels and serum creatinine of 1.0 mg/dl
      ('normal' range (0.5-1.2 mg/dl)). This case illustrates impressively the lack of
      serum creatinine as an ideal kidney function test, because it is depending on
      muscle mass and there is no interindividual normal range.

PMID- 22605837
TI  - Pilocarpine induced acute angle closure.
AB  - A 34-year-old Caucasian female with advanced primary angle closure glaucoma
      developed acute angle closure following administration of g.pilocarpine 2% given
      as preparation for laser peripheral iridotomies. Subsequent investigations
      supported an underlying diagnosis of spherophakia with no systemic associations.
      She required peripheral iridotomies, bilateral clear lens extractions and left
      cyclodiode laser to control her intraocular pressures. This case highlights the
      situations when pilocarpine should be given with caution and also the increasing
      role of phacoemulsification as an alternative to filtration surgery in primary
      angle closure glaucoma management.

PMID- 22605839
TI  - Mesenteric paraganglioma's: an important differential diagnosis in intra
      abdominal tumours.

PMID- 22605838
TI  - Mycobacterium intracellulare infection in non-HIV infected patient in a region
      with a high burden of tuberculosis.
AB  - Data on non-tuberculous Mycobacteria (NTM) infection in non-HIV patients in
      Tanzania are scarce. However, NTM infections are emerging in Africa as in many
      parts of the world. Healthcare providers and physicians working in high
      tuberculosis incidence regions should also consider NTM as one of the
      differential diagnosis. A 35-year-old Tanzanian man presented with history of
      cough, fever, chest pain and night sweats for 4 weeks. The patient had a history
      of tuberculosis 4 years ago. On physical examination, there were no significant
      findings. Sputum smears were positive for acid fast bacilli, while Xpert MTB/RIF
      showed negative results. Culture and subsequent differentiation confirmed
      Mycobacterium intracellulare infection. With no specific national guidelines at
      our setting the patient received standard antituberculosis treatment and is kept
      under close follow-up.

PMID- 22605840
TI  - Congenital cytomegalovirus infection associated with development of neonatal
      emphysematous lung disease.
AB  - A 26-week-gestation infant developed cystic lung changes which required lobar
      resection at 6 weeks of age. Lung histology showed cytomegalovirus (CMV)
      inclusion bodies. The authors present the radiology and histology images of this
      case and review the literature regarding congenital CMV infection and cystic lung
      disease. Lung disease caused by CMV is typically a diffuse pneumonitis. This is
      the first reported case of congenital CMV infection causing emphysematous lung
      disease to develop in the neonatal period. The case raises awareness of CMV as a
      possible cause of cystic lung lesions in newborns.

PMID- 22605841
TI  - Hypersensitivity reaction to human papillomavirus vaccine due to polysorbate 80.
AB  - A 17-year-old girl reported generalised urticaria, eyelid angioedema, rhino
      conjunctivitis, dyspnoea and wheezing 1 h after third intramuscular
      administration of quadrivalent human papilloma virus vaccine (Gardasil). She was
      treated with antihistamine, and corticosteroids with prompt relief of rhinitis
      and dyspnoea, while urticaria and angioedema lasted 24 h. Intradermal test with
      Gardasil, which contains polysorbate 80 (PS80), resulted positive, while skin
      tests with the bivalent vaccine were negative. Prick test performed with PS80
      resulted positive in the patient and negative in ten healthy controls. The CD203
      basophil activation test result was negative for PS80 at all the tested dilutions
      and specific IgE was not found. As flu vaccine was recommended, the authors skin
      tested two flu vaccine, one containing PS80 (Fluarix, GSK), which resulted
      positive and another flu vaccine with no adjuvant or preservative (Vaxigrip,
      Sanofi Pasteur MSD), which gave negative results. The patient then received
      Vaxigrip without adverse reactions.

PMID- 22605842
TI  - Crouzon syndrome.

PMID- 22605843
TI  - The thrombosed brachial-cephalic fistula used for renal dialysis--a cautionary
      note.
AB  - Arteriovenous fistulae (AVF) are commonly required for dialysis prior to renal
      transplantation, and are subsequently left insitu, even if thrombosed. The
      authors present one of two patients in whom progressive digital ischaemia
      occurred, and was initially overlooked, many years following formation of an AVF.
      The patient was surgically explored and clot protruding from the thrombosed vein
      into the brachial artery was noted. The arterial defect was closed with a vein
      patch and histological examination of the fistula confirmed clot. The patient
      recovered satisfactorily and remained well 6 months postoperatively. The authors
      would suggest that embolisation from a thrombosed AVF does occur, has a
      significant morbidity and can lead to digital loss. Furthermore, transplant
      patients are usually long suffering and will often put up with what they describe
      as 'aches and pains' as part of their illness. The authors suggest those patients
      suffering with evidence of ischaemia warrant excision of the fistula.

PMID- 22605844
TI  - Extra-pulmonary primary multidrug-resistant tubercular lymphadenitis in an HIV
      negative patient.
AB  - A 28-year-old woman without any history of prior antituberculosis treatment
      presented with cervical lymphadenopathy and a cold abscess near medial end of
      clavicle of 5 months duration. Pus culture and sensitivity revealed Mycobacterium
      tuberculosis resistant to rifampicin and isoniazid. Thus she was diagnosed as a
      case of primary multidrug-resistant tuberculosis and treated with second line
      drugs according to culture susceptibility pattern. On completion of therapy,
      patent showed good clinical response. This case highlights the observation that
      even extra-pulmonary primary multidrug-resistant tuberculosis can be successfully
      treated with currently available second line drugs.

PMID- 22605845
TI  - Stroke preceding autoimmune encephalitis with neuronal potassium channel
      antibody.
AB  - Autoimmune encephalitis related to voltage-gated potassium channel (VGKC)
      antibodies can occur as a complication of cancer but, more frequently, as a non
      paraneoplastic disorder. The prompt recognition and treatment could mitigate the
      morbidity associated with this entity, but the broad-spectrum of neurological
      manifestations often makes the diagnosis a challenge. The authors describe, here,
      a unique case of autoimmune encephalitis related to VGKC antibodies preceded by
      an ischaemic stroke. Conditions associated with the stroke (infection, seizures,
      metabolic disturbances) had delayed the diagnosis. The authors suggest that
      autoimmune encephalitis needs to be taken into consideration as part of a
      differential diagnosis in patients with prolonged encephalopathy following an
      ischaemic stroke. Infection may trigger an inflammatory response. In addition,
      the rupture of blood brain barrier that occurs in stroke may have a pathogenic
      role by allowing antibodies to gain access to the central nervous system.

PMID- 22605846
TI  - Disseminated histoplasma and CMV infection presenting as subacute intestinal
      obstruction in an immunocompromised patient.
AB  - Histoplasma in patients with impaired cellular immunity can disseminate to
      various organs and is known as progressive disseminated histoplasmosis. Similarly
      cytomegalovirus (CMV) is the most common opportunistic pathogen in an
      immunocompromised host. The authors report an older male with symptoms and
      radiological evidence of subacute intestinal obstruction. The patient had
      concerns for compromised immune system as he was on chronic prednisone and
      methotrexate therapy. Follow-up colonoscopy revealed a stricture in the proximal
      ascending colon. Biopsy of the stricture revealed ulcer with granulomatous
      inflammation including well-formed granulomas and an infiltrate of histiocytes
      within the lamina propria. Special stains on the specimen showed fungal
      structures consistent with Histoplasma capsulatum. Immunochemistry showed
      presence of CMV in the tissue. The patient had good response to antimicrobial
      therapy and did not have progression of intestinal obstruction. This case
      highlights the need to consider infectious pathology in immunocompromised
      patients presenting with obstructive symptoms.

PMID- 22605847
TI  - Lymphangioleiomyomatosis: a radiological diagnosis.

PMID- 22605848
TI  - Acute community acquired Aspergillus pneumonia in a presumed immunocompetent
      host.
AB  - Infection from Aspergillus results in a wide range of diseases from simple
      Aspergillus pneumonia to fatal invasive Aspergillosis. Though the fungus is known
      to predominantly affect the immunocompromised host, it has also been known to
      cause acute pneumonia in immunocompetent hosts which is invariably fatal. It
      presents as an acute pneumonia with bilateral chest infiltrates on radiograph.
      Early clinical suspicion and microbiological identification by measures such as
      broncho alveolar lavage and initiation of therapy with voricanozole significantly
      increase the chances of survival. In this article the authors discuss a case of
      acute community acquired Aspergillus pneumonia in an immunocompetent host who
      survived due to early identification and prompt treatment with appropriate
      antifungal medication.

PMID- 22605849
TI  - Diphtheroids as a cause of endocarditis in a haemodialysis patient.
AB  - The authors report a fatal case of Corynebacterium sp. endocarditis.
      Corynebacterium spp. are non-sporulating, pleomorphic Gram-positive bacilli. In
      particular the authors have identified a species of Corynebacterium very closely
      related to C striatum. This is C simulans. The authors were able to identify the
      genus and species using various phenotypic tests. Highlighted here is the
      importance of identifying diphtheroids as a significant pathogen in the
      appropriate setting and the need to start antibiotic therapy if this is
      suspected.

PMID- 22605850
TI  - Paediatric acute basilar thrombosis successfully treated with intravenous
      alteplase.
AB  - Acute ischaemic stroke has significant attendant morbidity and is one of the top
      ten causes of childhood death. It requires prompt investigation and management,
      however little is known about the safety and efficacy of acute thrombolytic
      therapies in childhood arterial ischaemic stroke. The authors report a case of a
      13-year-old girl with an acute basilar thrombosis, successfully treated with
      intravenous recombinant tissue plasminogen activator and discuss the management
      of paediatric arterial ischaemic stroke.

PMID- 22605851
TI  - Palatal avulsion injury by a foreign body in a child.
AB  - A 6-year-old girl who claimed to have fallen while playing with metal rod that
      resulted in palatal avulsion injuries was presented. Neither of the parents was
      around when the incidence happened. She was brought to the hospital because of
      pain, bleeding from the mouth, drooling of saliva mixed with blood and inability
      to feed or phonate appropriately. Examinations of the oral cavity revealed a
      triangular area of avulsion in the posterior aspect of the hard palate extending
      to the soft palate. She had examination under anaesthesia and wound repaired with
      3-0 vicryl interrupted sutures after thorough wound debridement. She did well and
      was discharged from the clinic.

PMID- 22605852
TI  - Paediatric talus fracture.
AB  - Paediatric talus fractures are rare injuries resulting from axial loading of the
      talus against the anterior tibia with the foot in dorsiflexion. Skeletally
      immature bone is less brittle, with higher elastic resistance than adult bone,
      thus the paediatric talus can sustain higher forces before fractures occur.
      However, displaced paediatric talus fractures and those associated with high
      energy trauma have been associated with complications including avascular
      necrosis, arthrosis, delayed union, neurapraxia and the need for revision
      surgery. The authors present the rare case of a talar neck fracture in a
      skeletally immature young girl, initially missed on radiological review. However,
      clinical suspicion on the part of the emergency physician, repeat examination and
      further radiographic imaging revealed this rare paediatric injury.

PMID- 22605853
TI  - Intravenous immunoglobulin in treatment of Clostridium difficile colitis.
AB  - Clostridium difficile infection is the most common infectious cause of healthcare
      acquired diarrhoea. Severe infections cause therapeutic challenges for healthcare
      providers. Various novel treatment modalities are currently being explored for
      treatment of severe disease. The authors report a 70-year-old female who
      presented to the emergency room with 1 week history of fever, watery diarrhoea,
      diffuse abdominal pain and weakness. C difficile toxin was detected in the stool
      and abdominal CAT scan showed extensive colonic wall thickening. The patient was
      started on intravenous metronidazole along with oral vancomycin. Due to the
      severity of the infection the patient was given intravenous immunoglobin for 4
      consecutive days. The patient had vast improvement in her clinical symptoms with
      resolution of the multi-organ system failure. It is currently considered that the
      predominant intravenous immunoglobin's mechanism of action is through binding and
      neutralisation of toxin A by IgG antitoxin A antibodies.

PMID- 22605854
TI  - An unusual case of hyperthyroidism associated with jaundice and hypercalcaemia.
AB  - A 51-year-old woman with rheumatoid arthritis presented with a 3 month history of
      painless jaundice and significant weight loss and constipation. Laboratory values
      were consistent with hyperthyroidism, cholestatic jaundice and parathyroid
      hormone-independent hypercalcaemia. Three months after beginning of methimazole,
      euthyroidism was achieved and serum adjusted calcium, total and direct bilirubin
      levels were normal.

PMID- 22605855
TI  - Isolated bilateral upper lobar anomalous pulmonary venous connection--a rare
      anomaly confirmed on CT imaging.

PMID- 22605856
TI  - A father with postpartum psychosis.
AB  - Postpartum psychosis is a rare, however severe mood disorder in the perinatal
      period. It is most commonly associated with postpartum bipolar disorder. The
      author reports a case where a male patient with psychosis was admitted to the
      psychiatric unit 5 days after his wife gave birth to their male child. The
      patient was very concerned about the well being of his child and was afraid that
      something bad would happen to his child. The patient was diagnosed with an acute
      manic episode with psychotic symptoms and treated with olanzapine and lithium.
      The patient has been continued on therapeutic dose of lithium without any relapse
      of the symptoms, 3 months after the initial episode. The role of psychological
      stress in precipitating such a severe mood or psychotic disorder needs to be
      highlighted.

PMID- 22605857
TI  - Rosuvastatin-induced pemphigoid.
AB  - Statins are widely prescribed medications and very well tolerated. Rosuvastatin
      is another member of this drug used to treat dyslipidaemia. It is a competitive
      inhibitor of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase.
      Immunobullous disease is usually idiopathic but can be drug-induced. Both
      idiopathic and iatrogenic forms share common clinical and immunohistological
      features. The authors report a case of pemphigoid induced by rosuvastatin, a
      commonly prescribed medication. To our knowledge, there is limited report on
      rosuvastatin associated with pemphigoid in the literature.

PMID- 22605858
TI  - Lymphangioleiomyomatosis: a radiological diagnosis.

PMID- 22605859
TI  - Visceral leishmaniasis in immunosuppressed Caucasian patient.
AB  - A 64-year-old man was admitted with fever, weight loss, fatigue and night sweats.
      He was known to have rheumatoid arthritis and had been taking methotrexate for 1
      year. He had worked in Saudi Arabia until 1994 and had been living in Spain for 6
      months every year. Clinical examination showed an enlarged spleen. Routine
      investigations showed pancytopaenia. Serial blood cultures were negative. CT scan
      confirmed splenomegaly and was otherwise unremarkable. Bone marrow biopsy
      revealed Leishmania amastigote consistent with a diagnosis of visceral
      leishmaniasis. After discussing with the hospital for tropical diseases (HTD), he
      was started on liposomal amphotericin B. Following two infusions of amphotericin
      B, he started improving as his fever, night sweats and weakness had settled. He
      was then discharged and followed up in HTD clinic 4 weeks later where he was
      found to be consistently improving.

PMID- 22605860
TI  - Ulcerative colitis presenting as acute infectious gastroenteritis with a
      paralytic ileus.
AB  - A 15-year-old girl who presented with signs of acute infectious gastroenteritis,
      just as two members of her family is described. As the patient did not improve, a
      sigmoidoscopy was performed and the diagnosis of ulcerative colitis (UC) was
      made. Our hypothesis is that an infection triggered the development of UC. Her
      paralytic ileus was probably triggered by the increased nitric oxide produced in
      the macrophages and smooth muscles of the inflamed bowel.

PMID- 22605861
TI  - CMV infection complicating the diagnosis of Crohn's disease in an immunocompetent
      patient.
AB  - Cytomegalovirus (CMV) affects the gastrointestinal tract commonly; however CMV
      colitis is uncommon in patients who are not severely immunocompromised. The
      author reports a 51-year-old Caucasian female who was admitted to the hospital
      with exacerbation of her chronic diarrhoea. CAT scan of the abdomen and pelvis
      showed thickening of the wall of the terminal ileum with inflammatory stranding
      and follow-up colonoscopy showed extensive circumferential ulceration in the
      terminal ileum. Biopsies confirmed diagnosis of CMV infection and the patient was
      started on appropriate antimicrobial agents. CMV viremia showed response to the
      medication; however the patient's intestinal symptoms failed to improve. Nodular
      lesions consistent with erythema nodusum were noticed and promethus test was
      consistent with Crohn's disease. The patient showed good response to
      immunosuppressive therapy. CMV infections are known to exacerbate symptoms of
      inflammatory bowel disease and hence Crohn's disease should be suspected in an
      immunocompetent patient presenting with CMV ileitis.

PMID- 22605862
TI  - Erectile dysfunction as an initial presentation of diabetes discovered by taking
      sexual history.
AB  - This case, as an important clinical reminder, will illustrate improvement of a
      patient's quality of life and care in chronic diseases through sexual history
      taking in the primary care setting. The case report also includes recommended
      investigation for erectile dysfunction (ED). Family physicians need to maintain
      awareness of sexual dysfunction as part of the history taking during a general
      medical investigation to avoid leaving sexual issues untreated including ED. If
      left untreated, ED can lead to psychological trauma, frustration and lower self
      esteem. Additionally, ED is associated with major comorbidities such as
      cardiovascular disease, hypertension, dyslipidaemia, psychological conditions and
      diabetes mellitus. Thus, appropriately identifying this medical condition may
      lead prompt diagnoses and treatment of other major diseases.

PMID- 22605863
TI  - Small bowel evisceration through the anus--report of a case and review of
      literature.
AB  - An 84-year-old lady with a history of chronic recurrent rectal prolapse,
      presented to accident and emergency with a significant portion of small bowel and
      mesentery protruding out of her anus. The small bowel was not contained within
      peritoneum, nor was this a pararectal herniation. On examination of the rectum, a
      longitudinal tear was found in the anterior rectal wall, through which the small
      bowel had prolapsed. Hours after reducing the small bowel back into the anus, it
      prolapsed a second time. Due to multiple co-morbidities, this patient was not fit
      for surgery. The defect was temporarily repaired on the ward and the patient
      treated with aggressive antibiotic therapy. The patient continued to deteriorate,
      became septic, acidotic, hypotensive and died a day later.

PMID- 22605864
TI  - Traumatic left anterior descending to pulmonary trunk fistula.

PMID- 22605865
TI  - Intraventricular metastases from small cell carcinoma of the lung.
AB  - Small cell lung carcinoma (SCLC) represents 15-20% of all lung cancers. It is
      characterised by rapid growth and early metastatic dissemination. Generally, the
      prognosis of these patients is poor. When brain metastases develop, the prognosis
      is even poorer. Most of these cases present parenchymal metastases; however,
      intraventricular dissemination may also occur although it is very uncommon. To
      our knowledge the case reported here is the first showing multiple synchronic
      intraventricular dissemination from SCLC.

PMID- 22605866
TI  - Acute paradoxical reaction of cervical tuberculous lymphadenitis prompted by a
      misuse of etimicin sulphate.
AB  - A 45-year-old HIV-negative man was treated with intravenous etimicin sulphate for
      an unintentionally found, non-tender neck mass at a local outpatient clinic. His
      symptoms seemed improved initially. However, the unilateral mass subsequently
      became enlarged quickly and painful. Spontaneous discharge occurred after
      admission to our department. The smear of the pus from surgical drainage was
      positive for acid-fast bacilli and the presence of Mycobacterium tuberculosis was
      confirmed by culture. He was diagnosed with an acute paradoxical reaction (PR) of
      cervical tuberculous lymphadenitis. Our case was unusual in that acute PR of
      tuberculosis was caused by receiving single aminoglycoside agent which has not
      been proven to have therapeutic effect on TB infection and it is also the first
      case of PR induced by etimicin. The patient recovered well from a 6-month
      antituberculosis chemotherapy.

PMID- 22605867
TI  - Acute corneal hydrops mimicking full thickness perforation.
AB  - A 26-year-old Caucasian female with keratoconus presented with an acutely painful
      and red left eye. Visual acuity on presentation was 3/60. Slit lamp examination
      revealed localised Descemet's membrane break with iris partially plugging it.
      There was a bulging stromal cyst which would intermittently flatten and reform.
      The appearance when the cyst was flattened mimicked a full thickness corneal
      perforation. However, no obvious overlying epithelial defect was detected and an
      intermittent leakage through micro-perforations in the corneal epithelium was the
      probable cause of the variable appearance. The anterior chamber reformed and iris
      plug freed following an insertion of a bandage contact lens and taped eyelid. On
      follow-up, the Descement's membrane had healed with visual acuity improving to
      6/18. Our case illustrates the importance of identifying corneal hydrops
      mimicking a full thickness perforation as conservative management has a greater
      chance of recovery.

PMID- 22605868
TI  - Incarcerated foreign body in the vagina--a metal bangle used as a pessary.
AB  - Long-forgotten vaginal pessaries get incarcerated in the vagina and their removal
      poses problems. A 60-year-old postmenopausal woman presented with foul smelling
      purulent discharge per vaginum and stress incontinence. Speculum examination
      revealed foul smelling white discharge per vaginum and a friable vaginal wall
      which bled on touch. The anterior portion of a metal ring deeply embedded in the
      vagina was seen. The cervix appeared normal. Attempts of removal by traction
      under local infiltration failed and resulted in bleeding. Biopsy from the tissue
      covering the ring reported no evidence of malignancy. She was treated with broad
      spectrum antibiotics for 1 week and the metallic ring was removed without any
      complications under general anaesthesia using electrocautery. It was found to be
      a metallic bangle with design. It is essential to gently cauterise and release
      the fibrosis over the incarcerated foreign body to achieve safe removal.

PMID- 22605869
TI  - Single incision thoracoscopic sympathectomy for hyperhidrosis.
AB  - Thoracal sympatectomy for hyperhidrosis and vasospastic vascular diseases is a
      rare method of surgical treatment. Three patients (1 male, 2 female; mean age
      27.6; between 25 and 30) with palmar hyperhidrosis and/or axillary and dorsal
      hyperhidrosis who underwent single port thoracoscopic sympatectomy were analysed
      for age, sex, time of operation room, intraoperative and postoperative
      complications and length of hospital stay. Mean operating room time was 70 min
      (between 30 and 120 min). Mean length of hospital stay was 1 day. No
      postoperative complications were noted. Single incision laparoscopic surgery for
      hyperhidrosis is a safe method of treatment and an alternative to laparoscopy.

PMID- 22605870
TI  - Neonatal lupus syndrome in a Nigerian child.
AB  - Neonatal lupus is a rare syndrome resulting from passively transferred maternal
      autoantibodies during pregnancy. A male infant was delivered at term to a 29-year
      old primiparous woman who was diagnosed of systemic lupus erythematosus 2 years
      earlier and had detectable levels of autoantibodies (antinuclear antibody (ANA),
      anti-dsDNA, anti-Ro and anti-La/SSB) in second trimester. However, the pregnancy
      was otherwise uneventful. He presented at the age of 8 week with a widespread
      hypopigmented macular rash on the trunk and patchy alopecia involving the hair
      line and the occipito-parietal regions of 3 weeks duration, anaemia and
      symptomatic thrombocytopaenia. Serologic test for autoantibodies was positive for
      ANA and anti-La/SSB. Further evaluation was normal. He was managed conservatively
      with blood products and topical corticosteroids. Mother was also advised to avoid
      direct exposure to sunlight and fluorescent light. Haematological parameters
      gradually normalised over 2 months and the skin lesions resolved completely by
      the age of 6 months.

PMID- 22605871
TI  - Tumefactive demyelination associated with systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a chronic inflammatory multi-system disease
      characterised by varied clinical manifestation and immunological abnormalities.
      The clinical presentation of the disorder has wide spectra, from an asymptomatic
      presentation to a severe life-threatening disease affecting several organs. The
      sole manifestation of lupus erythematosus could be neurological syndrome, where
      diagnosis of SLE is difficult to establish. The authors intended to report a
      young female, who initially developed left-sided hemiparesis due to tumefactive
      demyelination, later on diagnosed as case of SLE. The association of tumefactive
      demyelination and SLE has not been previously reported in the literature.

PMID- 22605872
TI  - Recurrent ectopic pregnancy in a woman suffering from infertility due to male
      factor presented with heterotopic pregnancy.
AB  - Heterotopic pregnancy is the simultaneous occurrence of intrauterine and
      extrauterine pregnancies. A 27-year-old third gravida with history of two ectopic
      pregnancies, presented with cramping pain in pelvis radiating to left side and
      bleeding from vagina. Ultrasonographic diagnosis of heterotopic pregnancy was put
      forward. Unfortunately intrauterine component of heterotopic pregnancy resulted
      in blighted ovum and linear salpingostomy was done for left-sided tubal
      pregnancy.

PMID- 22605873
TI  - Spontaneous occlusion of the circle of Willis in a young woman with epilepsy:
      epileptic-type Moyamoya disease.
AB  - The authors report a case of a 31-year-old woman from India with history of
      seizure disorder who presented with sudden onset right hemiparesis and right
      sided upper motor neuron type facial palsy. No identifiable risk factors were
      noted on admission and all laboratory investigations were negative. MR
      angiography helped in arriving at the diagnosis of moyamoya disease as the
      aetiology of her symptoms.

PMID- 22605874
TI  - Abdominal swelling in two teenage girls: two case reports of massive ovarian
      tumours in puberty.
AB  - The following report describes two 15-year-old girls with a giant abdominal
      swelling. Signs and symptoms differed between those two girls, as serum tumour
      markers showed different elevation patterns. Additional investigations including
      a CT scan and a MRI scan were performed and revealed masses originating from the
      ovary. Histopathological evaluation after cystectomy showed a mature teratoma and
      a mucinous cystadenoma.

PMID- 22605875
TI  - Septic arthritis and osteomyelitis in a 10-year-old boy, caused by Fusobacterium
      nucleatum, diagnosed with PCR/16S ribosomal bacterial DNA amplification.
AB  - A 10-year-old boy presented with an atypical non-febrile septic
      arthritis/osteomyelitis. He was unresponsive to routine antibiotic treatment with
      flucloxacillin/gentamicin as the pain and fluid collection increased. Synovial
      fluid cultures are negative and gram stain remained negative. Only after PCR/16S
      ribosomal bacterial DNA amplification a Fusobacterium nucleatum could be
      detected, and antibiotic therapy switched to clindamycin with rapid response.
      Septic osteomyelitis and arthritis are relatively rare but important infections
      in children needing prompt treatment, and should be considered when a child
      complaints about joint or bone pain without prior recent trauma. Skin bacteria
      are the most prevalent causative organisms, whereas Fusobacteria or other
      anaerobic, Gram-negative microorganisms are very seldom encountered. If cultures
      remain negative and the patients responds insufficiently to empiric treatment,
      PCR/16S ribosomal bacterial DNA amplification can be useful to detect the
      causative microorganisms.

PMID- 22605876
TI  - Longitudinally extensive transverse myelitis associated with dengue fever.
AB  - Longitudinally extensive transverse myelitis (LETM) is usually associated with
      neuromyelitis optica and other autoimmune and inflammatory disorders but this is
      the first report linking it with dengue fever. Dengue infection can cause a
      variety of neurological complications which may result in poor recovery and long
      term disability. The authors report here a patient who developed LETM in the para
      infectious stage of dengue fever. The patient had a complicated clinical course
      resulting in severe paraparesis and urinary retention. Treatment with
      immunoglobulins and antiviral agents supported by a spell of early intensive
      rehabilitation programme produced excellent results in terms of recovery.

PMID- 22605877
TI  - A clue to the diagnosis of TAPVD.
AB  - Total anomalous pulmonary venous drainage (TAPVD) is a rare form of congenital
      heart disease where all four pulmonary veins drain to the systemic venous
      circulation. A term infant was found to have low oxygen saturations on the
      neonatal check and he was admitted to the neonatal intensive care unit. An
      increasing oxygen requirement necessitated invasive ventilation. A blood gas
      taken from the umbilical venous catheter (UVC) showed a pO(2) of 28.1kPa - a
      finding that at the time was considered to be erroneous. An x-ray showed the UVC
      tip was located in the liver. The following day the baby was transferred to a
      cardiology centre where a diagnosis of unobstructed infracardiac TAPVD was made
      on echocardiography. In retrospect the unusually oxygenated venous gas was
      consistent with pulmonary venous return draining directly to the hepatic venous
      system. This could have provided a vital clue to diagnosis in a situation where
      an echocardiogram was not available.

PMID- 22605878
TI  - A 6-year-old boy with fever, rash and severe pneumonia.
AB  - The authors report a 6-year-old boy with fever, rash and cough. He was diagnosed
      with severe measles pneumonia and admitted to the paediatric intensive care unit
      with severe dyspnoea 8 days after symptom onset. He received intravenous
      antibiotics and high dose vitamin A. Three days later, he had recovered and was
      discharged home. He had not been vaccinated for measles, mumps and rubella
      according to the schedule. This case highlights the need for rapid diagnosis,
      appropriate treatment and determination of vaccination status of children with
      measles in order to prevent complications.

PMID- 22605879
TI  - A complex case of congenital cystic renal disease.
AB  - This case outlines the potential complexity of autosomal recessive polycystic
      kidney disease (ARPKD). It highlights the challenges involved in managing this
      condition, some of the complications faced and areas of uncertainty in the
      decision making process. With a paucity of published paediatric cases on this
      subject, this should add to the pool of information currently available.

PMID- 22605880
TI  - The American Family in Black and White: A Post-Racial Strategy for Improving
      Skills to Promote Equality.
AB  - In contemporary America, racial gaps in achievement are primarily due to gaps in
      skills. Skill gaps emerge early before children enter school. Families are major
      producers of those skills. Inequality in performance in school is strongly linked
      to inequality in family environments. Schools do little to reduce or enlarge the
      gaps in skills that are present when children enter school. Parenting matters,
      and the true measure of child advantage and disadvantage is the quality of
      parenting received. A growing fraction of American children across all race and
      ethnic groups is being raised in dysfunctional families. Investment in the early
      lives of children in disadvantaged families will help close achievement gaps.
      America currently relies too much on schools and adolescent remediation
      strategies to solve problems that start in the preschool years. Policy should
      prevent rather than remediate. Voluntary, culturally sensitive support for
      parenting is a politically and economically palatable strategy that addresses
      problems common to all racial and ethnic groups.

PMID- 22605882
TI  - Menstrual characteristics in some adolescent girls in Accra, Ghana.
AB  - BACKGROUND: Menstruation has a variable pattern within a few years of menarche
      which may not be well understood by many adolescent girls. Providing accurate
      information on menstruation is necessary to reduce anxiety, menstrual morbidity
      and improve reproductive health of these adolescents. OBJECTIVE: To determine the
      age at menarche, duration of menstruation, length of menstrual cycle, regularity
      of menstrual cycle, prevalence of dysmenorrhoea and sources of information on
      menstruation. SETTING: S(T) Mary's Senior Secondary School, Accra. METHODOLOGY:
      Cross-sectional descriptive study using self-administered questionnaire. RESULTS:
      Four hundred and fifty six girls whose ages ranged from 14-19 years with mean and
      median ages of 16 +/- 0.93 years and 16 years respectively were surveyed. Their
      ages at menarche ranged from 9 years to 16 years and the mean age at menarche was
      12.5 +/-1.28 years. Their menstrual cycle lengths ranged from 21-35 days with
      mean menstrual cycle length of 27.9+/- 0.9 days; the mode and median were both 28
      days. The mean duration of menstrual flow was 4.9 days with mode and median of 5
      days. Seventy one percent (n=449) had menses lasting 3-5 days while 27.2% had
      menses lasting over 5 days. Some 24% (n=409) had irregular menses six months
      after their menarche and 59.6% (n=453) were experiencing menses with clots. The
      prevalence of dysmenorrhoea was 74.4% (n=453). Some 80.2% (n=378) of the girls
      got counselling and education on care for their menses from their parents.
      CONCLUSION: The age at menarche and other menstrual characteristics observed in
      this study are similar to adolescent menstrual characteristics described by
      studies in other populations in the world.

PMID- 22605883
TI  - Breast cancer in Kumasi, Ghana.
AB  - BACKGROUND: Breast cancer is the leading cause of cancer deaths in Ghanaian
      women. OBJECTIVE: To describes the characteristics of breast cancer patients
      attending the Komfo Anokye Teaching Hospital in Kumasi, Ghana. METHOD: The study
      was conducted at the Komfo Anokye Teaching Hospital. Between July 1st 2004 and
      June 30(th) 2009 patients presenting with breast lumps were assessed by clinical
      examination, imaging studies and pathological examination. Relevant clinical and
      pathological were recorded prospectively data on all patients with
      microscopically proven breast cancer. The cancers were graded according to the
      modified Bloom-Richardson system. Tissue immunoperoxidase stains for oestrogen,
      progesterone receptors and c-erb2 oncogene were performed with commercially
      prepared antigens and reagents. RESULTS: Nineteen thousand four hundred and
      twenty-three (19,423) patients were seen during the study period. There were 330
      (1.7%) patients with histologically proven breast cancer. The mean age was 49.1
      years. A palpable breast lump was detected in 248 patients (75.2%). Two hundred
      and eighty-one patients (85.2%) presented with Stages III and IV, 271 (82.1%)
      invasive and 230 (85.2%) high grade carcinomas. Oestrogen and progesterone
      receptors were positive in 32 and 9 cases respectively. Her2 protein was positive
      in 11 cases. CONCLUSION: In Kumasi, as in other parts of Ghana, breast cancer
      affects mostly young pre-menopausal who present with advanced disease. The
      cancers have unfavourable prognostic features and are unlikely to respond to
      hormonal therapy.

PMID- 22605884
TI  - Lipid disorders in hospital attendants in Kumasi, Ghana.
AB  - BACKGROUND: Lipid disorders are common worldwide and contribute to a significant
      proportion of the burden of atherosclerotic cardiovascular diseases. OBJECTIVES:
      To determine the prevalence of lipid disorders among patients reporting at Komfo
      Anokye Teaching Hospital (KATH), Kumasi, Ghana. DESIGN: Cross-sectional study.
      SETTING: Directorate of Medicine and Polyclinic outpatient clinics of KATH.
      PARTICIPANTS: A total of 424 patients, 20 years and over reporting for the first
      time to KATH were recruited. 77 had neither diabetes mellitus (DM) nor systemic
      hypertension (HPT) (controls), 94 had only DM, 109 had only HPT and 144 had both.
      METHODS: A questionnaire was administered after informed consent. Anthropometric
      measurements were then taken and blood investigations including total cholesterol
      (TC), high-density lipoprotein cholesterol (HDL) and triglycerides (TG) were
      done. Low-density lipoprotein cholesterol (LDL) was calculated using the
      Friedwald formula. The atherogenic index or ratio was the ratio of TC to HDL.
      RESULTS: The prevalence of lipid abnormalities was 60% for high TC, 32% for high
      TG, 17% for low HDL and 61% for high LDL. The mean (+/- standard deviation) TC
      was 5.33 (+/- 1.31) mmol/L, mean TG was 1.52 (+/- 0.81) mmol/L, mean HDL was 1.65
      (+/- 0.57) mmol/L and mean LDL was 3.42 (+/- 1.22) mmol/L. The mean atherogenic
      index was 3.40 and 9% of the participants had an atherogenic index more than or
      equal to 5. CONCLUSION: The prevalence of lipid disorders was high in adult
      patients in Kumasi and there is the need to increase awareness, screening,
      detection, treatment and control of these disorders.

PMID- 22605885
TI  - Evaluating the medical care of child sexual abuse victims in a general hospital
      in Ibadan, Nigeria.
AB  - OBJECTIVES: Evaluation of the medical care provided to victims of Child Sexual
      Abuse (CSA). DESIGN: A retrospective cross sectional study. SETTING: The general
      outpatient clinic of a 150 bed secondary health care facility in Ibadan, Nigeria.
      PARTICIPANTS: Children < 18 years who were treated as Victim's sexual assault.
      MAIN OUTCOME MEASURE: Investigations and treatment prescribed for CSA victims.
      RESULTS: The median age of victims was 12 years (range 3-17 years). All were
      females and 33.3% had attained menarche. Many (68.1%) had torn hymen; of these,
      16.3 % also had vaginal lacerations and bleeding. Children>10 years more often
      had torn hymen (P<0.001). Vaginal swab microscopy was done in 84.0% of those with
      torn hymen. About 60% of victims had retroviral screening done (all were non
      reactive) the retroviral screening of the perpetrator was requested in only case.
      None of the patients received post exposure prophylaxis for HIV. Of those with
      signs of vaginal penetration who had also attained menarche 12.2% had emergency
      contraceptives prescribed. Treatment of victims consisted mostly of antibiotics-
      47.2% and analgesics--37.5% with only 15.3% of patients proffered any form of
      counselling. CONCLUSIONS: There is a still a huge gap between the health care
      needs of victims of CSA and the medical services provided for victims of CSA. The
      use of a treatment protocol and additional training for health care providers in
      the management of CSA victims is encouraged.

PMID- 22605886
TI  - Sexual risk behaviour among HIV-positive persons in Kumasi, Ghana.
AB  - OBJECTIVES: To assess the prevalence and predictors of sexual risk behaviours
      among HIV-positive individuals in clinical care in Kumasi, Ghana. DESIGN: Cross
      sectional survey of 267 (43 males and 224 females) HIV-positive individuals
      attending Kumasi South Regional Hospital. METHODS: An interviewer-administered
      questionnaire was used to asses demographic and health characteristics, HIV/AIDS
      knowledge, attitudes, and beliefs and sexual risk behaviours. RESULTS: Forty-four
      percent of the sample reported having sex after testing positive for HIV. Of the
      175 participants with regular sex partners, 24% had HIV-positive partners.
      Majority (67%) had HIV-negative partners (serodiscordant couples) or partners of
      unknown status. More than half (51%) of the study population with regular sex
      partners reported that they had unprotected anal or vaginal sex. Participants who
      scored < 50% on the HIV/AIDS knowledge scale were 90% less likely to have used
      condoms during their last sexual intercourse. Disclosure of HIV status was
      associated with protective patterns of condom use (OR=2.2; 95% CI: 1.3-12.9).
      Participants on ARV were 80% less likely to have used condoms during the last
      sexual intercourse (OR=0.2; 95% CI: 0.04-0.6). CONCLUSION: The high rates of
      sexual risk behaviour among HIV-positive individuals in this sample place others
      at risk of HIV infection. It also places these HIV positive individuals at risk
      for infection with sexually transmitted infections and super-infection with other
      HIV strains. These findings highlight the need to integrate HIV prevention in
      routine medical care in Ghana.

PMID- 22605887
TI  - Hospital all-risk emergency preparedness in Ghana.
AB  - OBJECTIVE: This paper assessed the emergency preparedness programs of health
      facilities for all-risks but focused on Road Traffic Accidents, (RTA) resulting
      in surge demand. It adopted W. H. O checklist covering hospital preparedness,
      equipment, manpower and surge capacity planning as best practices for the
      mitigation of public health emergencies. METHOD: This is a cross-sectional study
      of purposively selected health facilities. The method used consisted of site
      visit, questionnaire survey, literature and internet review. The W. H. O.
      standard for emergency preparedness of health facilities was used to evaluate and
      assess the nation's hospitals surge capacity programs. The study was conducted
      between March-June, 2010. A total of 22 district and regional health facilities
      including teaching hospitals participated in the study. All 10 regions of the
      country were covered. RESULT: These were: (1) many of the nation's hospitals were
      not prepared for large RTA's resulting in surge demands, and did not possess
      general emergency preparedness programs. (2) The hospitals' respective abilities
      to handle large scale RTA's were compromised by the lack of competent medical and
      allied health personnel and adequate supplies. DISCUSSION: The inadequacies of
      the hospital system in responding to emergencies raise serious public health
      concerns. The biggest challenge facing the hospitals in their emergency
      intervention is the lack of pre-emergency and emergency preparedness plans as
      well as the coordination of the hospitals response mechanisms. CONCLUSION: The
      paper ended with recommendations on how the nation's hospitals and their
      supervisory agencies could improve emergency preparedness.

PMID- 22605888
TI  - Recurrent respiratory papillomatosis: the Korle-Bu experience.
AB  - BACKGROUND: Recurrent respiratory papillomatosis is a benign disease of the aero
      digestive tract which is caused by the human papilloma virus type 6 and 11 and
      mainly affects children. OBJECTIVE: The aim of this study is to describe the
      pattern of recurrent respiratory papillomatosis at the E.N.T Unit Korle Bu
      Teaching Hospital, Accra. METHOD: This is a retrospective study of theatre
      records of patients managed for respiratory papillomata from January 1995 to
      December 2004 at the E.N.T Unit of Korle Bu Teaching Hospital, Accra which is a
      tertiary facility. These records were studied and we obtained information on
      gender, age, number of surgeries and the presence of tracheotomy. RESULTS: Sixty
      nine patients were identified over the period. Thirty-three males and 36 females
      with a M:F ratio 1:1.1, and ages ranging from 2 to 54 years. The mean age was
      12.3 years and a median age of 8.5 years.Children less than 10 years accounted
      for 69% and 46.4% had repeated surgery with overall tracheotomy rate of 14.5%.
      CONCLUSIONS: Recurrent Respiratory Papillomatosis is primarily a paediatric
      disease. Locally, its distribution is comparable to others in the sub region and
      worldwide and surgery is the mainstay of treatment.

PMID- 22605889
TI  - Central retinal artery occlusion following peribulbar anesthesia for pterygium
      excision.
AB  - Pterygium is a common ocular surface pathology in tropical environments. In the
      early stages, it may be managed medically with topical anti-inflammatory agents
      and ocular lubricants. However as the disease progresses, surgical excision
      becomes necessary and several anaesthetic methods may be used to assist this. We
      share our experience of a 30-year old woman who underwent uneventful pterygium
      excision using peribulbar lignocain injection with adrenaline. She developed
      sudden blindness due to central retinal artery occlusion with macular infarction.
      While peribulbar anaesthesia is generally safe, a remote risk of retinal vascular
      accident exists and its routine use should be done with caution. Where possible
      topical anaesthesia with or without intra-lesional injection be employed.

PMID- 22605890
TI  - ?
AB  - We establish a long time soliton asymptotics for a nonlinear system of wave
      equation coupled to a charged particle. The coupled system has a six-dimensional
      manifold of soliton solutions. We show that in the large time approximation, any
      solution, with an initial state close to the solitary manifold, is a sum of a
      soliton and a dispersive wave which is a solution to the free wave equation. It
      is assumed that the charge density satisfies Wiener condition which is a version
      of Fermi Golden Rule, and that the momenta of the charge distribution vanish up
      to the fourth order. The proof is based on a development of the general strategy
      introduced by Buslaev and Perelman: symplectic projection in Hilbert space onto
      the solitary manifold, modulation equations for the parameters of the projection,
      and decay of the transversal component.

PMID- 22605891
TI  - Bioorganometallic Chemistry of Molybdenocene Dichloride and Its Derivatives.
AB  - The potential application of metallocene complexes into the cancer research was
      established by the pioneer work of Kopf-Maeir and Kopf in the late 1970s. The
      combination of organometallic chemistry and biochemistry created a new research
      area: bioorganometallic chemistry. Bioorganometallic chemistry has developed
      rapidly in the last thirty years leading to application of organometallic species
      into diagnostic, sensors, immunoassays and anticancer research among others. This
      review focuses on the bioorganometallic chemistry of molybdenocene dichloride and
      its derivatives as metal-based anticancer drugs. The anticancer properties of
      molybdenocene dichloride and its derivatives are described as well as the
      mechanism of action, aqueous and coordination chemistry, and molybdenocene
      biomolecule interactions.

PMID- 22605893
TI  - When One Size Doesn't Fit All.

PMID- 22605892
TI  - Protein Cysteines Map to Functional Networks According to Steady-state Level of
      Oxidation.
AB  - The cysteine (Cys) proteome serves critical roles in protein structure, function
      and regulation, and includes key targets in oxidative mechanisms of disease.
      Thioredoxins maintain Cys residues in thiol forms, and previous research shows
      that the redox potential of thioredoxin in mitochondria and nuclei is more
      reduced than cytoplasm, suggesting that proteins in these compartments may have
      different steady-state oxidation. This study measured fractional oxidation of 641
      peptidyl Cys residues from 333 proteins in HT29 cells by mass spectrometry.
      Average oxidation of cytoplasmic, nuclear and mitochondrial proteins was similar
      (15.8, 15.5, 14%, respectively). Pathway analysis showed that more reduced
      cytoplasmic Cys were in proteins associated with the cytoskeleton, more reduced
      nuclear Cys with Ran signaling and RNA post-transcriptional modifcation, and more
      reduced mitochondrial Cys with energy metabolism, cell growth and cell
      proliferation. More oxidized cytoplasmic Cys included associations with PI3/Akt,
      Myc-mediated apoptosis and 14-3-3-mediated signaling. Weaker associations of
      oxidized nuclear and mitochondrial Cys occurred with granzyme B signaling and
      intermediary metabolism, respectively. Thus, steady-state peptidyl Cys oxidation
      is associated with functional pathways rather than simply with organellar
      distribution. This suggests that oxidative mechanisms of disease could target
      functional pathways or networks rather than individual proteins or subcellular
      compartments.

PMID- 22605894
TI  - Under Scrutiny: FDA's REMS for Opioids: Acceptance or Rejection by Stakeholders
      Will Influence Congress.

PMID- 22605895
TI  - Misprogramming patient-controlled analgesia levels causes dosing errors.

PMID- 22605896
TI  - New drugs/drug news.

PMID- 22605897
TI  - Pharmaceutical approval update.

PMID- 22605898
TI  - Indacaterol (arcapta neohaler) for chronic obstructive pulmonary disease.

PMID- 22605899
TI  - The FDA's Social Media Guidelines Are Here ... Were They Worth the Wait?

PMID- 22605900
TI  - Cost analysis before and after implementation of a computerized physician order
      entry order form for enoxaparin.
AB  - OBJECTIVE: The authors sought to analyze the impact of a computerized physician
      order entry (CPOE) order form for enoxaparin sodium injection (Lovenox) to reduce
      the daily cost of drug therapy by switching appropriate patients to once-daily
      enoxaparin administration. METHODS: The study population included patients older
      than 18 years of age who had been treated with enoxaparin from September 1 to
      December 31, 2008 (the pre-order form implementation group) and from March 1 to
      June 30, 2009 (the post-order form implementation group). The wholesale
      acquisition cost was used to determine the cost of enoxaparin per day.
      Appropriate dosing was established by chart review. RESULTS: The post
      implementation group showed a trend toward a higher cost of enoxaparin therapy
      per day compared with the pre-implementation group (P = 0.23). There was a non
      significant increase in appropriate dosing after implementation of the order form
      from 64.5% before implementation to 71.5% after implementation (P = 0.13). In the
      overall cohort, although the authors controlled for other factors that could
      influence cost, patients who received the appropriate dose per protocol were 3.2
      times more likely (95% confidence interval, 1.8-5.9; P = 0.001) to have lower
      enoxaparin drug costs per day of therapy. CONCLUSION: The use of a CPOE
      enoxaparin order form did not reduce the daily cost of therapy.

PMID- 22605901
TI  - 34th annual san antonio breast cancer symposium and 53rd american society of
      hematology annual meeting and exposition.

PMID- 22605902
TI  - Tall man letters are gaining wide acceptance.

PMID- 22605903
TI  - Congress is likely to approve generic drug user fees: action should spur faster
      FDA approvals.

PMID- 22605904
TI  - Pharmaceutical approval update.

PMID- 22605905
TI  - New drugs/drug news.

PMID- 22605907
TI  - FDA weighs updating its bar-code mandate: hospital pharmacies worry about
      implementation.

PMID- 22605906
TI  - Roflumilast (daliresp): a novel phosphodiesterase-4 inhibitor for the treatment
      of severe chronic obstructive pulmonary disease.

PMID- 22605908
TI  - Interviews With Two Women's Health Experts On the Use of Estrogen Therapies.

PMID- 22605910
TI  - Cardiovascular research technologies 2012.

PMID- 22605909
TI  - Multiple sclerosis review.

PMID- 22605911
TI  - Biologics and specialty pharmacy health care survey: implications for p&t
      committees.

PMID- 22605912
TI  - BrilintaTM (ticagrelor) Tablets: A P2Y(12) platelet inhibitor indicated to reduce
      the rate of thrombotic cardiovascular events in patients with acute coronary
      syndrome (ACS).

PMID- 22605913
TI  - The Sex Check: The Development of an HIV-Prevention Service to Address the Needs
      of Latino MSM.
AB  - The Sex Check is a brief, telephone-delivered, HIV-prevention intervention
      tailored for individuals who are at high risk of HIV infection or transmission
      but who are neither reducing their risk on their own nor seeking support for this
      purpose. Because the intervention is delivered on a one-to-one basis, permits
      anonymity, is marketed to "men who have sex with men," and is brief, it may be
      particularly responsive to cultural, structural, and attitudinal barriers to
      serving Latino MSM. Because many Latino MSM continue to engage in high risk
      sexual behaviors, developing and testing prevention interventions with this
      population is a public health priority.

PMID- 22605914
TI  - Retinol dehydrogenase 13 protects the mouse retina from acute light damage.
AB  - PURPOSE: To investigate whether retinol dehydrogenase 13 (RDH13) can protect the
      retina from acute light-induced damage. METHODS: We generated Rdh13 knockout mice
      using molecular biologic methods and assessed the associated morphological and
      functional changes under room-light conditions by hematoxylin-eosin (H&E),
      transmission electron microscopy (TEM), and scotopic electroretinography. Then,
      the light-damage model was established by exposure to diffuse white light (3,000
      lx) for 48 h. Twenty-four h after light exposure, H&E was used for the
      histological evaluation. The thickness of the outer-plus-inner-segment and the
      outer nuclear layer was measured on sections parallel to the vertical meridian of
      the eye. An electroretinography test was performed to assess the functional
      change. Furthermore, the impairment of mitochondria was detected by TEM. Finally,
      the expression of cytochrome c (CytC) and other apoptosis-related proteins was
      detected by western blot. RESULTS: We found that there was no obvious difference
      in phenotype or function between Rdh13 knockout and wild-type mice. In Rdh13(-/-)
      mice subjected to intense light exposure, the photoreceptor outer-plus-inner
      segment and outer nuclear layer were dramatically shorter, and the amplitudes of
      a- and b-waves under scotopic conditions were significantly attenuated.
      Distinctly swollen mitochondria with disrupted cristae were observed in the
      photoreceptor inner segments of Rdh13(-/-) mice. Increased expression levels of
      CytC, CytC-responsive apoptosis proteinase activating factor-1 (Apaf-1) and
      caspases 3, and other mitochondria apoptosis-related genes (nuclear factor-kappa
      B P65 [P65] and B-cell lymphoma 2-associated X protein [Bax]) were observed in
      Rdh13(-/-) mice. CONCLUSIONS: Rdh13 can protect the retina against acute light
      induced retinopathy. The mechanism may involve inhibition of the mitochondrial
      apoptosis pathway.

PMID- 22605915
TI  - A new mutation in the RP1L1 gene in a patient with occult macular dystrophy
      associated with a depolarizing pattern of focal macular electroretinograms.
AB  - PURPOSE: To determine whether a mutation in the RP1-like protein 1 (RP1L1) gene
      is present in a Japanese patient with sporadic occult macular dystrophy (OMD) and
      to examine the characteristics of focal macular electroretinograms (ERGs) of the
      patient with genetically identified OMD. METHODS: An individual with OMD
      underwent detailed ophthalmic clinical evaluations including focal macular ERGs.
      Mutation screening of all coding regions and flanking intron sequences of the
      RP1L1 gene were performed with DNA sequencing analysis in this case with OMD.
      RESULTS: A new RP1L1 mutation (c.3596 C>G in exon 4) was identified. The variant
      c.3596 C>G in exon 4 resulted in the substitution of cysteine for serine at amino
      acid position 1199. The serine at position 1199 is well conserved among the RP1L1
      family in other species. Four out of five computational assessment tools
      predicted that this mutation is damaging to the protein function. This mutation
      was not present in 294 control alleles. The waveform of focal macular ERGs
      recorded from the patient with OMD had a depolarizing pattern, simulating the ERG
      waveforms observed after the hyperpolarizing bipolar cell activity is blocked.
      CONCLUSIONS: We have demonstrated in a Japanese patient the possibility that
      sporadic OMD may also be caused by an RP1L1 mutation. The waveform of focal
      macular ERGs elicited from the OMD patient with the RP1L1 mutation showed a
      depolarizing pattern. This characteristic is the same as reported for the focal
      macular ERGs of OMD.

PMID- 22605916
TI  - Role of Lysyl oxidase-like 1 gene polymorphisms in Pakistani patients with
      pseudoexfoliative glaucoma.
AB  - PURPOSE: Single nucleotide polymorphisms (SNPs) rs1048661 (p.R141L) and rs3825942
      (p.G153D) in the lysyl oxidase-like 1 (LOXL1) gene have been previously reported
      to be associated with pseudoexfoliation glaucoma (PEXG) in various Asian and
      European populations, but these SNPs have not yet been studied in the Pakistani
      population. Therefore the aim of the present study was to investigate the
      association of these two coding LOXL1 SNPs in Pakistani PEXG patients. METHODS:
      One hundred twenty-eight Pakistani patients diagnosed with PEXG and 180 healthy
      controls were recruited for the study. Genomic DNA was extracted and both SNPs
      were genotyped by direct sequencing. Association of genotype and allele
      frequencies with PEXG were analyzed using the Chi-square (chi(2)) test. RESULTS:
      Genotype and allele frequencies of both rs1048661 and rs3825942 were found to be
      significantly associated with PEXG. The GG genotypes of both LOXL1 SNPs were
      associated with an increased risk of developing PEXG. In addition the G alleles
      of rs1048661 and rs3825942 confer an increased risk for PEXG with an odds ratio
      (OR) of 2.98 (95% CI 1.94-4.57) and OR 6.83 (95% CI 2.94-16.67), respectively.
      CONCLUSIONS: A significant association was found for the G allele of rs1048661
      and rs3825942 in PEXG patients of Pakistani origin.

PMID- 22605917
TI  - In vivo imaging of choroidal angiogenesis using fluorescence-labeled cationic
      liposomes.
AB  - PURPOSE: Precise monitoring of active angiogenesis in neovascular eye diseases
      such as age-related macular degeneration (AMD) enables sensitive use of
      antiangiogenic drugs and reduces adverse side effects. So far, no in vivo imaging
      methods are available to specifically label active angiogenesis. Here, we report
      such a technique using fluorophore-labeled cationic liposomes (CL) detected with
      a standard clinical in vivo scanning laser ophthalmoscope (SLO). METHODS: C57Bl/6
      mice underwent laser coagulations at day 0 (d0) to induce choroidal
      neovascularization (CNV). Liposomes labeled with Oregon green, rhodamine (Rh), or
      indocyanine green (ICG) were injected into the tail vein at various time points
      after laser coagulation, and their fluorescence was observed in vivo 60 min later
      using an SLO, or afterwards in choroidal flatmounts or cryosections. RESULTS: SLO
      detected accumulated fluorescence only in active CNV lesions with insignificant
      background noise. The best signal was obtained with CL-ICG. Choroidal flatmounts
      and cryosections of the eye confirmed the location of retained CL in CNV lesions.
      Neutral liposomes, in contrast, showed no accumulation. CONCLUSIONS: These
      results establish fluorophore-labeled CL as high affinity markers to selectively
      stain active CNV. This novel, non-invasive SLO imaging technique could improve
      risk assessment and indication for current intraocular antiangiogenic drugs in
      neovascular eye diseases, as well as monitor therapeutic outcomes. Labeling of
      angiogenic vessels using CL can be of interest not only for functional imaging in
      ophthalmology but also for other conditions where localization of active
      angiogenesis is desirable.

PMID- 22605918
TI  - Androgen regulation of gene expression in human meibomian gland and conjunctival
      epithelial cells.
AB  - PURPOSE: Androgens exert a significant influence on the structure, function
      and/or pathophysiology of the meibomian gland and conjunctiva. We sought to
      determine whether this hormone action involves the regulation of epithelial cell
      gene expression in these tissues. METHODS: Immortalized human meibomian gland and
      conjunctival epithelial cells were treated with placebo or dihydrotestosterone
      (DHT) and processed for molecular biologic procedures. Gene expression was
      evaluated with BeadChips and data were analyzed with bioinformatic and
      statistical software. RESULTS: Androgen treatment significantly influenced the
      expression of approximately 3,000 genes in immortalized human meibomian gland and
      conjunctival epithelial cells. The nature of DHT action on gene activity was
      predominantly cell-specific. Similarly, DHT exerted a significant, but primarily
      cell-specific, influence on many gene ontologies and Kyoto Encyclopedia of Genes
      and Genomes (KEGG) pathways. These included groups of genes related, for example,
      to lipid dynamics, innate immunity, cell cycle, Janus kinase (JAK)-signal
      transducer and activator of transcription (stat) cascades, oxidative
      phosphorylation, the proteasome, and mammalian target of rapamycin (mTOR), Wnt,
      and peroxisome proliferator-activated receptor (PPAR) signaling. CONCLUSIONS: Our
      findings support our hypothesis that androgens regulate gene expression in human
      meibomian gland and conjunctival epithelial cells. Our ongoing studies are
      designed to determine whether many of these genes are translated and play a role
      in the health and well being of the eye.

PMID- 22605919
TI  - Corneal crosslinking with genipin, comparison with UV-riboflavin in ex-vivo
      model.
AB  - PURPOSE: To investigate the efficacy and safety of Genipin and UV-riboflavin
      crosslinking (UV-CLX) in corneal crosslinking. METHODS: Porcine eyes were
      separated in groups for each crosslinker, genipin 0.25% UV-CLX (clinical
      crosslinking procedure), glutaraldehyde 0.1% (gold standard crosslinker), and
      control eyes. Intraocular pressure (IOP) was continuously monitored by a pressure
      sensor cannulated to the anterior chamber and the volume was changed. The changes
      in ocular pressure as a function of change of the ocular volume were evaluated.
      Ocular rigidity was calculated as the exponential of polynomial quadratic fit.
      Endothelial damage was evaluated in a viability assay with alizarin red staining
      as the changes in cell counts. RESULTS: Significant changes in IOP were observed
      in the globes were the cornea was stiffened with genipin and UV-CLX treatment
      (volume 200 MUl: Genipin 19.4 mmHg, UVCRX 18.8 mmHg, glutaraldehide 23.9 mmHg,
      versus control 14.7 mmHg, and 400 MUl genipin 31.5 mmHg, UV-CLX 26.0 mmHg,
      glutaraldehide 37.3 mmHg versus control 18.7 mmHg). The mean ocular ridigity
      coefficient was genipin 0.0078 mmHg/MUl, UV-CLX 0.0065 mmHg/MUl, glutaraldehide
      0.0092 mmHg/MUl, and 0.0046 mmHg/MUl for control eyes. Endothelial cell damage
      was 5.9+/-1.8% (control), 10.3+/-1.7% (UV-CLX), 9.4+/-1.5% (Genipin 0.25%), and
      40.1+/-6.2% (glutaraldehide). Some granules were observed in the UV-CLX group.
      Reduction of keratocites was observed in the UV CRX crosslinking. CONCLUSIONS:
      Corneal crosslinking was similar between UV-CLX and genipin with minimal toxicity
      to endothelial cells. Stiffened corneas by any method induced substancially
      higher IOP elevation when ocular volume is increased.

PMID- 22605920
TI  - The timing of goniosynechialysis in treatment of primary angle-closure glaucoma
      combined with cataract.
AB  - PURPOSE: To compare the clinical effects of phacoemulsification (PHACO) combined
      with goniosynechialysis (GSL) at different times in the treatment of primary
      angle-closure glaucoma (PACG) combined with cataract. METHODS: Before surgery,
      one or more different kinds of anti-glaucoma medicines were used for 24 patients
      (32 eyes) of PACG combined with cataract. A combination of PHACO with GSL
      procedures were performed on both groups of patients. The patients were randomly
      divided into two groups: 17 patients with 21 eyes were in Group A (GSL performed
      before lens was removed) and 7 patients with 11 eyes in Group B (GSL after
      extraction of crystal cortex). Changes in visual acuity, intraocular pressure
      (IOP) and the depth of the center anterior chamber were observed before surgery
      and again at 1 month, 3 months, 6 months, and 12 months after surgery. RESULTS:
      The mean visual acuity of Group A and Group B was 1.13+/-0.75 and 0.93+/-0.50,
      respectively. There was no statistical difference between these two groups in
      visual acuity before surgery. At 1 month, 3 months, 6 months, and 12 months after
      surgery, the visual acuities in Group A were 0.57+/-0.33, 0.42+/-0.24, 0.30+/
      0.23, 0.35+/-0.28 and the visual acuities in Group B were 0.68+/-0.60, 0.38+/
      0.15, 0.40+/-0.17,0.33+/-0.13, and 0.37+/-0.06. Visual acuity after surgery was
      greatly improved in both groups. However, there was no difference between these
      two groups at the different points in time mentioned above. The mean IOP before
      surgery was 35.67+/-12.31 mmHg and 31.64+/-15.06 mmHg for Group A and Group B,
      respectively. At 1 month, 3 months, 6 months, and 12 months after surgery, the
      IOP were normalized and were significantly lower than before surgery, in group A
      and B. However, there was no difference in IOP between these groups at the
      different points in time as mentioned above. One year after surgery, the
      percentages of success in Group A and Group B were 86.0% and 90.0%, respectively,
      qualified success rates in Group A and Group B were 9.5% and 10.0%, respectively.
      The failure rate in Group A was 4.8%, and no one failed in Group B. In Group A,
      the number of medications pre-operation was 2.05+/-0.74. A trabeculectomy was
      performed on 1 eye, and anti-glaucoma medicines were used for 2 eyes after
      surgery to normalize IOP. In Group B, the number of medications pre-operation was
      2.18+/-0.87. One anti-glaucoma medicine- was used for 1 eyes. In different period
      after surgery, anterior chamber angles in Group A were all open. Narrow anterior
      chamber angles in different extents also were observed in 4 eyes in Group B. The
      mean depth of the center anterior chamber before surgery was 1.56+/-0.37 mmHg and
      1.72+/-0.35 mmHg for Group A and Group B, respectively. At 1 month, 3 months, 6
      months and 12 months after surgery, the center anterior chamber was deeper than
      that before surgery both in both groups . However, there was no difference in the
      center anterior chamber's depth between these groups at the different points in
      time mentioned above. CONCLUSIONS: For PACG patients with cataracts, surgery
      methods are shown to improve visual acuity, decrease IOP, and expand the anterior
      chamber angle. Regarding the opening extent of the anterior chamber angle,
      surgery performed on Group A achieved better results than Group B.

PMID- 22605921
TI  - Genome-wide association study of primary open angle glaucoma risk and
      quantitative traits.
AB  - PURPOSE: Primary open angle glaucoma (POAG) is a characteristic optic neuropathy
      which progresses to irreversible vision loss. Few genes have been detected that
      influence POAG susceptibility and other genes are therefore likely to be
      involved. We analyzed carefully characterized POAG cases in a genome-wide
      association study (GWAS). METHODS: We performed a GWAS in 387 POAG cases using
      public control data (WTCCC2). We also investigated the quantitative phenotypes,
      cup:disc ratio (CDR), central corneal thickness (CCT), and intra-ocular pressure
      (IOP). Promising single nucleotide polymorphisms (SNPs), based on various
      prioritisation criteria, were genotyped in a cohort of 294 further POAG cases and
      controls. RESULTS: We found 2 GWAS significant results in the discovery stage for
      association, one of which which had multiple evidence in the gene 'neural
      precursor cell expressed, developmentally down-regulated 9' (NEDD9; rs11961171,
      p=8.55E-13) and the second on chromosome 16 with no supporting evidence. Taking
      into account all the evidence from risk and quantitative trait ocular phenotypes
      we chose 86 SNPs for replication in an independent sample. Our most significant
      SNP was not replicated (p=0.59). We found 4 nominally significant results in the
      replication cohort, but none passed correction for multiple testing. Two of
      these, for phenotypes CDR (rs4385494, discovery p=4.51x10-5, replication p=0.029)
      and CCT (rs17128941, discovery p=5.52x10-6, replication=0.027), show the
      consistent direction of effects between the discovery and replication data. We
      also assess evidence for previously associated known genes and find evidence for
      the genes 'transmembrane and coiled-coil domains 1' (TMCO1) and 'cyclin-dependent
      kinase inhibitor 2B' (CDKN2B). CONCLUSIONS: Although we were unable to replicate
      any novel results for POAG risk, we did replicate two SNPs with consistent
      effects for CDR and CCT, though they do not withstand correction for multiple
      testing. There has been a range of publications in the last couple of years
      identifying POAG risk genes and genes involved in POAG related ocular traits. We
      found evidence for 3 known genes (TMCO1, CDKN2B, and S1 RNA binding domain 1
      [SRBD1]) in this study. Novel rare variants, not detectable by GWAS, but by new
      methods such as exome sequencing may hold the key to unravelling the remaining
      contribution of genetics to complex diseases such as POAG.

PMID- 22605922
TI  - Identification of GABA receptors in chick cornea.
AB  - PURPOSE: The cornea has an important role in vision, is highly innervated and
      many neurotransmitter receptors are present, e.g., muscarine, melatonin, and
      dopamine receptors. gamma-aminobutyric acid (GABA) is the most important
      inhibitory neurotransmitter in the retina and central nervous system, but it is
      unknown whether GABA receptors are present in cornea. The aim of this study was
      to determine if GABA receptors are located in chick cornea. METHODS: Corneal
      tissues were collected from 25, 12-day-old chicks. Real time PCR, western blot,
      and immunohistochemistry were used to determine whether alpha(1) GABA(A),
      GABA(B), and rho(1) GABA(C) receptors were expressed and located in chick cornea.
      RESULTS: Corneal tissue was positive for alpha(1) GABA(A) and rho(1) GABA(C)
      receptor mRNA (PCR) and protein (western blot) expression but was negative for
      GABA(B) receptor mRNA and protein. Alpha(1) GABA(A) and rho(1) GABA(C) receptor
      protein labeling was observed in the corneal epithelium using
      immunohistochemistry. CONCLUSIONS: These investigations clearly show that chick
      cornea possesses alpha(1) GABA(A), and rho(1) GABA(C) receptors, but not GABA(B)
      receptors. The purpose of the alpha(1) GABA(A) and rho(1) GABA(C) receptors in
      cornea is a fascinating unexplored question.

PMID- 22605923
TI  - 17-beta-estradiol inhibits hyperosmolarity-induced proinflammatory cytokine
      elevation via the p38 MAPK pathway in human corneal epithelial cells.
AB  - PURPOSE: To evaluate the effects of 17-beta-estradiol on hyperosmolar stress
      induced proinflammatory cytokine production of interleukin (IL)-6, IL-1, and
      tumor necrosis factor-alpha (TNF-alpha) in SV40-immortalized human corneal
      epithelial cells (hCECs) and the regulatory effects of the mitogen-activated
      protein kinase (MAPK) signaling pathways in this process. METHODS: SV40 hCECs
      cultured in normal osmolar media were switched to a higher osmolarity (450 mOsM)
      by adding NaCl with or without pretreatment with 17-beta-estradiol. Real-time
      polymerase chain reaction and ELISA were applied to characterize IL-6, IL-1, and
      TNF-alpha gene and protein expression. Cells were treated for 15-60 min, lysed in
      radioimmunoprecipitation assay (RIPA) buffer and subjected to a western blot with
      phospho (p)-specific antibodies against extracellular signal-regulated protein
      kinase 1/2 (ERK1/2), P38 kinase, and c-Jun N-terminal kinase 1/2 (JNK1/2).
      RESULTS: The expression and production of IL-6, IL-1, and TNF-alpha in SV40 hCECs
      increased when the media osmolarity was switched to 450 mOsM. Pretreatment with
      10(-10) M 17-beta-estradiol greatly inhibited the increased expression and
      production of IL-6, IL-1, and TNF-alpha induced by hyperosmolarity, whereas with
      the administration of SB203580 (10 MUM), an inhibitor of the p38 pathway, the
      inhibiting effect of 17-beta-estradiol disappeared. The western blot results
      showed that the increased phosphorylation level of p38 caused by hyperosmolarity
      was greatly inhibited by 17-beta-estradiol. CONCLUSIONS: 17-beta-estradiol
      greatly inhibited the expression and production of proinflammatory cytokines IL
      6, IL-1, and TNF-alpha, which were stimulated by hyperosmolarity in SV40
      immortalized hCECs. The results also suggested that the p38 MAPK signaling
      pathway was involved in the regulatory effects of estrogen on hCECs. These
      findings may contribute to an understanding of the etiologic roles and
      therapeutic implications of the hormone estrogen in dry eye disease.

PMID- 22605924
TI  - Transcriptome analysis using next generation sequencing reveals molecular
      signatures of diabetic retinopathy and efficacy of candidate drugs.
AB  - PURPOSE: To define gene expression changes associated with diabetic retinopathy
      in a mouse model using next generation sequencing, and to utilize transcriptome
      signatures to assess molecular pathways by which pharmacological agents inhibit
      diabetic retinopathy. METHODS: We applied a high throughput RNA sequencing (RNA
      seq) strategy using Illumina GAIIx to characterize the entire retinal
      transcriptome from nondiabetic and from streptozotocin-treated mice 32 weeks
      after induction of diabetes. Some of the diabetic mice were treated with
      inhibitors of receptor for advanced glycation endproducts (RAGE) and p38 mitogen
      activated protein (MAP) kinase, which have previously been shown to inhibit
      diabetic retinopathy in rodent models. The transcripts and alternatively spliced
      variants were determined in all experimental groups. RESULTS: Next generation
      sequencing-based RNA-seq profiles provided comprehensive signatures of
      transcripts that are altered in early stages of diabetic retinopathy. These
      transcripts encoded proteins involved in distinct yet physiologically relevant
      disease-associated pathways such as inflammation, microvasculature formation,
      apoptosis, glucose metabolism, Wnt signaling, xenobiotic metabolism, and
      photoreceptor biology. Significant upregulation of crystallin transcripts was
      observed in diabetic animals, and the diabetes-induced upregulation of these
      transcripts was inhibited in diabetic animals treated with inhibitors of either
      RAGE or p38 MAP kinase. These two therapies also showed dissimilar regulation of
      some subsets of transcripts that included alternatively spliced versions of
      arrestin, neutral sphingomyelinase activation associated factor (Nsmaf), SH3
      domain GRB2-like interacting protein 1 (Sgip1), and axin. CONCLUSIONS: Diabetes
      alters many transcripts in the retina, and two therapies that inhibit the
      vascular pathology similarly inhibit a portion of these changes, pointing to
      possible molecular mechanisms for their beneficial effects. These therapies also
      changed the abundance of various alternatively spliced versions of signaling
      transcripts, suggesting a possible role of alternative splicing in disease
      etiology. Our studies clearly demonstrate RNA-seq as a comprehensive strategy for
      identifying disease-specific transcripts, and for determining comparative
      profiles of molecular changes mediated by candidate drugs.

PMID- 22605925
TI  - A tapetal-like fundus reflex in a healthy male: evidence against a role in the
      pathophysiology of retinal degeneration?
AB  - PURPOSE: To report on the retinal function and structure in a 37-year-old male
      who presented with a tapetal-like reflex (TLR) indistinguishable from that seen
      in female carriers of X-linked retinitis pigmentosa (XLRP). METHODS: Clinical
      examination included dark adaptometry, full-field electroretinography (ERG),
      multifocal ERG, optical coherence tomography, and fundus autofluorescence
      photography. Molecular genetic testing included screening for known mutations in
      autosomal dominant, autosomal recessive, and X linked retinitis pigmentosa (RP)
      genes with a commercially available chip, and sequencing analysis of retinitis
      pigmentosa GTPase regulator (RPGR)-open reading frame 15 (ORF15). RESULTS: Fundus
      examination revealed a bilateral TLR, which is typical of female carriers of
      XLRP. Imaging studies and electrophysiological testing was unremarkable, except
      for a significant increase in full-field ERG amplitudes after prolonged dark
      adaptation as compared to after standard dark adaptation. Mutation screening was
      negative. CONCLUSIONS: TLR was found for the first time, to the best of our
      knowledge, in a male subject. There were no definitive signs of retinal
      degeneration, suggesting that this reflex in itself is not necessarily a
      precursor of the retinal degeneration that can be seen in female carriers of
      XLRP.

PMID- 22605926
TI  - Investigation of the influence of Arg555Trp and Thr538Pro TGFBI mutations on C
      terminal cleavage and cell endoplasmic reticulum stress.
AB  - PURPOSE: To gain insight into the mechanisms underlying the transforming growth
      factor-beta induced (TGFBI)-related corneal dystrophies and the influence of the
      Arg555Trp and Thr538Pro, TGFBI mutations on C-terminal cleavage and cell
      endoplasmic reticulum (ER) stress were investigated. METHODS: The Arg555Trp and
      Thr538Pro mutations known to be associated with corneal dystrophy granular type I
      and lattice corneal dystrophy, respectively, were introduced with the two
      sequential PCR site-directed mutagenesis technique. Wild-type and mutant TGFBI
      DNAs were cloned into the pcDNA3.1(-)/myc-his expression vector and overexpressed
      in HeLa and human corneal epithelial cells (HCE) with transient transfection.
      Transfection efficiency was measured by the expression of green fluorescent
      protein. Expression of the fusion proteins was measured with western blot
      analysis with anti-c-myc-tag and anti-TGFBI antibodies. For cell ER stress
      studies, the expression levels of GRP78/BiP in HeLa cells were analyzed with
      western blot analysis using an anti-GRP78 monoclonal antibody at 12, 24, and 48 h
      after either the wild-type or mutant plasmid was transfected. RESULTS: Arg555Trp
      and Thr538Pro mutant TGFBIp were detected with the anti-c-myc and anti-TGFBI
      antibodies, while wild-type TGFBIp was detected only with the anti-TGFBI
      antibody, indicating that the Arg555Trp and Thr538Pro mutations prevent the C
      terminal cleavage of TGFBIp. Moreover, no significant differences were seen in
      the expression levels of GRP78/BiP between the mutant and wild-type TGFBIp
      groups, suggesting that mutations in TGFBIp are unlikely to disrupt protein
      folding or induce cell ER stress. CONCLUSIONS: This is the first time that the
      influence of TGFBI mutants on C-terminal cleavage and cell ER stress has been
      illustrated. Corneal dystrophy-related mutations are more likely to disrupt the
      interaction of TGFBI with critical binding proteins than affect the whole protein
      structure.

PMID- 22605927
TI  - Mutations in TULP1, NR2E3, and MFRP genes in Indian families with autosomal
      recessive retinitis pigmentosa.
AB  - PURPOSE: To identify genes underlying autosomal recessive retinitis pigmentosa
      (ARRP) by homozygosity mapping. METHODS: Families with ARRP were recruited after
      complete ophthalmic evaluation of all members and diagnosis of RP by predefined
      criteria. Genomic DNA from affected members of 26 families was genotyped on
      Illumina single nucleotide polymorphism (SNP) 6.0 K arrays with standard
      procedures. Genotypes were evaluated for homozygous regions that were common and
      concordant between affected members of each family. The genes mapping to
      homozygous intervals within these families were screened for pathogenic changes
      with PCR amplification and sequencing of coding regions. Co-segegration of
      sequence changes with disease was determined within each pedigree, and each
      variation was tested for presence in 100 unrelated normal controls. RESULTS: A
      genome-wide scan for homozygosity showed homozygous regions harboring the tubby
      like protein 1 gene (TULP1; chromosome 6) in one family, the nuclear receptor
      subfamily 2, group E, member 3 gene (NR2E3; chromosome 15) in three families, and
      the membrane frizzled-related protein gene (MFRP; chromosome 11) in one family.
      Screening of the three genes in the respective families revealed homozygous
      disease-causing mutations in three families. These included a missense mutation
      in TULP1, a deletion-cum-insertion in NR2E3, and a single base deletion in MFRP.
      Patients from all three families had a rod-cone type of dystrophy with night
      blindness initially. The NR2E3 and MFRP genes were associated with fundus
      features atypical of RP. CONCLUSIONS: This study shows involvement of the TULP1,
      NR2E3, and MFRP genes in ARRP in Indian cases. Genome-wide screening with SNP
      arrays followed by a prioritized candidate gene evaluation is useful in
      identifying genes in these patients.

PMID- 22605928
TI  - Hyaluronic acid increases MMP-2 and MMP-9 expressions in cultured trabecular
      meshwork cells from patients with primary open-angle glaucoma.
AB  - PURPOSE: A depletion of hyaluronic acid (HA) in patients' eyes may be associated
      with primary open-angle glaucoma (POAG), but the exact mechanism remains unclear.
      We investigated the effect of HA on the expression of matrix metalloproteinases
      (MMP-2 and MMP-9) in cultured trabecular meshwork cells. METHODS: Trabecular
      meshwork cells were cultured from trabecular tissues obtained from the POAG
      patients aged 23 to 45. The mRNA expression of MMP-2 and MMP-9 was determined by
      reverse transcription-polymerase chain reaction, and the protein expression of
      MMP-2 and MMP-9 by gelatin zymography analysis and qualified by the gel
      electrophoresis image analysis in different HA concentrations. RESULTS: The
      expression of MMP-2 and MMP-9 by the two methods significantly increased with HA
      concentration in a dose-response manner. Mean values of the MMP-2 expression by
      the gelatin zymography analysis were 176, 264, 353, and 448 mg/ml, and mean
      values of the MMP-9 expression were 547, 659, 895, and 1,147 mg/ml, for HA
      concentration level of 0, 1, 3, and 6 mg/ml, respectively. CONCLUSIONS: In POAG
      trabecular meshwork cells, the level of HA concentration increases the activities
      of MMP-2 and MMP-9. The lack of HA in aqueous humor can result in a reduction in
      activities of MMPs and therefore may be involved in the pathogenesis of POAG.

PMID- 22605929
TI  - Clinical and molecular findings in three Lebanese families with Bietti
      crystalline dystrophy: report on a novel mutation.
AB  - PURPOSE: Bietti crystalline dystrophy (BCD) is a rare autosomal recessive
      disorder caused by mutation of the cytochrome P450, family 4, subfamily V,
      polypeptide 2 (CYP4V2) gene and characterized by retinal pigmentary abnormalities
      and scattered deposits of crystals in the retina and the marginal cornea. The aim
      of this study was to investigate the spectrum of mutations in CYP4V2 in Lebanese
      families, and to characterize the phenotype of patients affected with BCD.
      METHODS: Nine patients from three unrelated Lebanese families were clinically and
      molecularly investigated. Detailed characterization of the patients' phenotype
      was performed with comprehensive ophthalmic examination, color vision study,
      fundus photography, visual field testing, retinal fluorescein angiography,
      electroretinography, and electrooculography. One family was followed for 12
      years. The 11 exons of the CYP4V2 gene were sequenced. RESULTS: Symptoms
      consisting of night blindness, loss of paracentral visual field, and disturbed
      color vision were apparent during the third decade of life. Ophthalmoscopy
      revealed posterior pole crystalline deposits and areas of retinal pigment
      epithelium atrophy. Fluorescein angiography disclosed geographic areas of the
      pigment epithelium layer and choriocapillaris atrophy in the posterior pole and
      fundus periphery. The most striking findings were those of normal
      electroretinographic responses in some patients and clinical heterogeneity. Two
      mutations in CYP4V2 were found: p.I111T (c.332T>C) in exon 3 in two families and
      the novel p.V458M (c.1372G>A) mutation in exon 9 in one family. CONCLUSIONS:
      These patients are affected with Bietti crystalline dystrophy without corneal
      involvement. Variation in disease severity and electroretinographic responses
      suggests that environmental or additional genetic factors influence the course of
      the retinal disease. The CYP4V2 p.I111T (c.332T>C) mutant allele may be
      especially prevalent among patients with BCD in Lebanon, resulting from a single
      founder.

PMID- 22605930
TI  - The preservative polyquaternium-1 increases cytoxicity and NF-kappaB linked
      inflammation in human corneal epithelial cells.
AB  - PURPOSE: In numerous clinical and experimental studies, preservatives present in
      eye drops have had detrimental effects on ocular epithelial cells. The aim of
      this study was to compare the cytotoxic and inflammatory effects of the
      preservative polyquaternium-1 (PQ-1) containing Travatan (travoprost 0.004%) and
      Systane Ultra eye drops with benzalkonium chloride (BAK) alone or BAK-preserved
      Xalatan (0.005% latanoprost) eye drops in HCE-2 human corneal epithelial cell
      culture. METHODS: HCE-2 cells were exposed to the commercial eye drops Travatan,
      Systane Ultra, Xalatan, and the preservative BAK. Cell viability was determined
      using colorimetric MTT (3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyltetrazolium
      bromide) assay and by release of lactate dehydrogenase (LDH). Induction of
      apoptosis was measured with a using a colorimetric caspase-3 assay kit. DNA
      binding of the nuclear factor kappa B (NF-kappaB) transcription factor, and
      productions of the proinflammatory cytokines, interleukins IL-6 and IL-8, were
      determined using an enzyme-linked immunosorbent assay (ELISA) method. RESULTS:
      Cell viability, as measured by the MTT assay, declined by up to 50% after
      exposure to Travatan or Systane Ultra solutions which contain 0.001% PQ-1. BAK at
      0.02% rather than at 0.001% concentration evoked total cell death signs on HCE-2
      cells. In addition, cell membrane permeability, as measured by LDH release, was
      elevated by sixfold with Travatan and by a maximum threefold with Systane Ultra.
      Interestingly, Travatan and Systane Ultra activated NF-kappaB and elevated the
      secretion of inflammation markers IL-6 by 3 to eightfold and IL-8 by 1.5 to 3.5
      fold, respectively, as analyzed with ELISA. CONCLUSIONS: Eye drops containing PQ
      1 evoke cytotoxicity and enhance the NF-kappaB driven inflammation reaction in
      cultured HCE-2 cells. Our results indicate that these harmful effects of ocular
      solutions preserved with PQ-1 should be further evaluated in vitro and in vivo.

PMID- 22605931
TI  - Biodistribution and pharmacokinetics of a telodendrimer micellar paclitaxel
      nanoformulation in a mouse xenograft model of ovarian cancer.
AB  - BACKGROUND: A multifunctional telodendrimer-based micelle system was
      characterized for delivery of imaging and chemotherapy agents to mouse tumor
      xenografts. Previous optical imaging studies demonstrated qualitatively that
      these classes of nanoparticles, called nanomicelles, preferentially accumulate at
      tumor sites in mice. The research reported herein describes the detailed
      quantitative imaging and biodistribution profiling of nanomicelles loaded with a
      cargo of paclitaxel. METHODS: The telodendrimer was covalently labeled with 125I
      and the nanomicelles were loaded with 14C-paclitaxel, which allowed measurement
      of pharmacokinetics and biodistribution in the mice using microSPECT/CT imaging
      and liquid scintillation counting, respectively. RESULTS: The radio imaging data
      showed preferential accumulation of nanomicelles at the tumor site along with a
      slower clearance rate than paclitaxel formulated in Cremophor EL (Taxol(r)).
      Liquid scintillation counting confirmed that 14C-labeled paclitaxel sequestered
      in nanomicelles had increased uptake by tumor tissue and slower pharmacokinetics
      than Taxol. CONCLUSION: Overall, the results indicate that nanomicelle-formulated
      paclitaxel is a potentially superior formulation compared with Taxol in terms of
      water solubility, pharmacokinetics, and tumor accumulation, and may be clinically
      useful for both tumor imaging and improved chemotherapy applications.

PMID- 22605932
TI  - Labeling and exocytosis of secretory compartments in RBL mastocytes by
      polystyrene and mesoporous silica nanoparticles.
AB  - BACKGROUND: For a safe 'in vivo' biomedical utilization of nanoparticles, it is
      essential to assess not only biocompatibility, but also the potential to trigger
      unwanted side effects at both cellular and tissue levels. Mastocytes (cells
      having secretory granules containing cytokines, vasoactive amine, and proteases)
      play a pivotal role in the immune and inflammatory responses against exogenous
      toxins. Mastocytes are also recruited in the tumor stroma and are involved in
      tumor vascularization and growth. AIM AND METHODS: In this work, mastocyte-like
      rat basophilic leukemia (RBL) cells were used to investigate whether carboxyl
      modified 30 nm polystyrene (PS) nanoparticles (NPs) and naked mesoporous silica
      (MPS) 10 nm NPs are able to label the secretory inflammatory granules, and
      possibly induce exocytosis of these granules. Uptake, cellular retention and
      localization of fluorescent NPs were analyzed by cytofluorometry and microscope
      imaging. RESULTS: OUR FINDINGS WERE THAT: (1) secretory granules of mastocytes
      are accessible by NPs via endocytosis; (2) PS and MPS silica NPs label two
      distinct subpopulations of inflammatory granules in RBL mastocytes; and (3) PS
      NPs induce calcium-dependent exocytosis of inflammatory granules. CONCLUSION:
      These findings highlight the value of NPs for live imaging of inflammatory
      processes, and also have important implications for the clinical use of PS-based
      NPs, due to their potential to trigger the unwanted activation of mastocytes.

PMID- 22605933
TI  - Resveratrol-loaded solid lipid nanoparticles versus nanostructured lipid
      carriers: evaluation of antioxidant potential for dermal applications.
AB  - BACKGROUND: Excessive generation of radical oxygen species (ROS) is a contributor
      to skin pathologies. Resveratrol (RSV) is a potent antioxidant. Solid lipid
      nanoparticles (SLN) and nanostructured lipid carriers (NLC) can ensure close
      contact and increase the amount of drug absorbed into the skin. In this study,
      RSV was loaded into SLN and NLC for dermal applications. METHODS: Nanoparticles
      were prepared by high shear homogenization using Compritol 888ATO, Myglyol,
      Poloxamer188, and Tween80. Particle size (PS), polydispersity index (PI), zeta
      potential (ZP), drug entrapment efficiency (EE), and production yield were
      determined. Differential scanning calorimetry (DSC) analysis and morphological
      transmission electron microscopy (TEM) examination were conducted. RSV
      concentration was optimized with cytotoxicity studies, and net intracellular
      accumulation of ROS was monitored with cytofluorimetry. The amount of RSV was
      determined from different layers of rat abdominal skin. RESULTS: PS of uniform
      RSV-SLN and RSV-NLC were determined as 287.2 nm +/- 5.1 and 110.5 nm +/- 1.3,
      respectively. ZP was -15.3 mV +/- 0.4 and -13.8 mV +/- 0.1 in the same order. The
      drug EE was 18% higher in NLC systems. TEM studies showed that the drug in the
      shell model was relevant for SLN, and that the melting point of the lipid in NLC
      was slightly lower. Concentrations below 50 MUM were determined as suitable RSV
      concentrations for both SLN and NLC in cell culture studies. RSV-NLC showed less
      fluorescence, indicating less ROS production in cytofluorometric studies. Ex vivo
      skin studies revealed that NLC are more efficient in carrying RSV to the
      epidermis. CONCLUSION: This study suggests that both of the lipid nanoparticles
      had antioxidant properties at a concentration of 50 MUM. When the two systems
      were compared, NLC penetrated deeper into the skin. RSV-loaded NLC with smaller
      PS and higher drug loading appears to be superior to SLN for dermal applications.

PMID- 22605935
TI  - Fabrication of pillared PLGA microvessel scaffold using femtosecond laser
      ablation.
AB  - One of the persistent challenges confronting tissue engineering is the lack of
      intrinsic microvessels for the transportation of nutrients and metabolites. An
      artificial microvascular system could be a feasible solution to this problem. In
      this study, the femtosecond laser ablation technique was implemented for the
      fabrication of pillared microvessel scaffolds of polylactic-co-glycolic acid
      (PLGA). This novel scaffold facilitates implementation of the conventional cell
      seeding process. The progress of cell growth can be observed in vitro by optical
      microscopy. The problems of becoming milky or completely opaque with the
      conventional PLGA scaffold after cell seeding can be resolved. In this study,
      PLGA microvessel scaffolds consisting of 47 MUm * 80 MUm pillared branches were
      produced. Results of cell culturing of bovine endothelial cells demonstrate that
      the cells adhere well and grow to surround each branch of the proposed pillared
      microvessel networks.

PMID- 22605934
TI  - Chitosan-Pluronic nanoparticles as oral delivery of anticancer gemcitabine:
      preparation and in vitro study.
AB  - Nanoparticles have proven to be an effective delivery system with few side
      effects for anticancer drugs. In this study, gemcitabine-loaded nanoparticles
      have been prepared by an ionic gelation method using chitosan and Pluronic((r)) F
      127 as a carrier. Prepared nanoparticles were characterized using dynamic light
      scattering, Fourier transform infrared spectroscopy (FT-IR), differential
      scanning calorimetry (DSC), scanning electron microscopy, and transmission
      electron microscopy. Different parameters such as concentration of sodium
      tripolyphosphate, chitosan, Pluronic, and drug on the properties of the prepared
      nanoparticles were evaluated. In vitro drug release was studied in phosphate
      buffered saline (PBS; pH = 7.4). The cytotoxicity of the nanoparticles was
      assayed in the HT-29 colon cancer cell line. The mucoadhesion behavior of the
      nanoparticles was also studied by mucus glycoprotein assay. The prepared
      nanoparticles had a spherical shape with positive charge and a mean diameter
      ranging between 80 to 170 nm. FT-IR and DSC studies found that the drug was
      dispersed in its amorphous form due to its potent interaction with nanoparticle
      matrix. Maximum drug encapsulation efficiency was achieved at 0.4 mg/mL
      gemcitabine while maximum drug loading was 6% obtained from 0.6 mg/mL
      gemcitabine. An in vitro drug release study at 37 degrees C in PBS (pH = 7.4)
      exhibited a controlled release profile for chitosan-Pluronic((r)) F-127
      nanoparticles. A cytotoxicity assay of gemcitabine-loaded nanoparticles showed an
      increase in the cytotoxicity of gemcitabine embedded in the nanoparticles in
      comparison with drug alone. The mucoadhesion study results suggest that
      nanoparticles could be considered as an efficient oral formulation for colon
      cancer treatment.

PMID- 22605936
TI  - Mesoporous silica nanoparticles as a compound delivery system in zebrafish
      embryos.
AB  - Silica nanoparticles can be efficiently employed as carriers for therapeutic
      drugs in vitro. Here, we use zebrafish embryos as a model organism to see whether
      mesoporous silica nanoparticles (MSNPs) can be incorporated to deliver compounds
      in vivo. We injected 35-40 nL (10 mg/mL) of custom-synthesized, fluorescently
      tagged 200 nm MSNPs into the left flank, behind the yolk sac extension, of 2-day
      old zebrafish embryos. We tracked the distribution and translocation of the MSNPs
      using confocal laser scanning microscopy. Some of the particles remained
      localized at the injection site, whereas others entered the bloodstream and were
      carried around the body. Embryo development and survival were not significantly
      affected by MSNP injection. Acridine orange staining revealed that MSNP
      injections did not induce significant cell death. We also studied cellular immune
      responses by means of lysC::DsRED2 transgenic embryos. MSNP-injected embryos
      showed infiltration of the injection site with neutrophils, similar to controls
      injected with buffer only. In the same embryos, counterstaining with L-plastin
      antibody for leukocytes revealed the same amount of cellular infiltration of the
      injection site in embryos injected with MSNPs or with buffer only. Next, we used
      MSNPs to deliver two recombinant cytokines (macrophage colony-stimulating factor
      and receptor for necrosis factor ligand) to zebrafish embryos. These proteins are
      known to activate cells involved in bone remodeling, and this can be detected
      with the marker tartrate-resistant acid phosphatase. Coinjection of these
      proteins loaded onto MSNPs produced a significant increase in the number of
      tartrate-resistant acid phosphatase-positive cells after 2-3 days of injection.
      Our results show that MSNPs can be used to deliver bioactive compounds into
      zebrafish larvae without producing higher mortality or gross evidence of
      teratogenicity.

PMID- 22605937
TI  - The role of cholesterol-sphingomyelin membrane nanodomains in the stability of
      intercellular membrane nanotubes.
AB  - Intercellular membrane nanotubes (ICNs) are highly curved tubular structures that
      connect neighboring cells. The stability of these structures depends on the inner
      cytoskeleton and the cell membrane composition. Yet, due to the difficulty in the
      extraction of ICNs, the cell membrane composition remains elusive. In the present
      study, a raft marker, ostreolysin, revealed the enrichment of cholesterol
      sphingomyelin membrane nanodomains along ICNs in a T24 (malignant) urothelial
      cancer cell line. Cholesterol depletion, due to the addition of methyl-beta
      cyclodextrin, caused the dispersion of cholesterol-sphingomyelin membrane
      nanodomains and the retraction of ICNs. The depletion of cholesterol also led to
      cytoskeleton reorganization and to formation of actin stress fibers. Live cell
      imaging data revealed the possible functional coupling between the change from
      polygonal to spherical shape, cell separation, and the disconnection of ICNs. The
      ICN was modeled as an axisymmetric tubular structure, enabling us to investigate
      the effects of cholesterol content on the ICN curvature. The removal of
      cholesterol was predicted to reduce the positive spontaneous curvature of the
      remaining membrane components, increasing their curvature mismatch with the tube
      curvature. The mechanisms by which the increased curvature mismatch could
      contribute to the disconnection of ICNs are discussed.

PMID- 22605939
TI  - The Bird Flu Threat - Why Aren't We Worrying?

PMID- 22605938
TI  - Uptake and transport of a novel anticancer drug-delivery system: lactosyl
      norcantharidin-associated N-trimethyl chitosan nanoparticles across intestinal
      Caco-2 cell monolayers.
AB  - In this paper, novel liver-targeting nanoparticles (NPs), lactosyl-norcantharidin
      (Lac-NCTD)-associated N-trimethyl chitosan (TMC) NPs (Lac-NCTD-TMC-NPs), were
      prepared using ionic cross-linkage. The physical properties, particle size, and
      encapsulation efficiency of the nanoparticles were then investigated. The
      continuous line of heterogeneous human epithelial colorectal adenocarcinoma cells
      (Caco-2) cell monolayer model was used to study the transport mechanism of Lac
      NCTD, and the effects of factors such as time, temperature, pH level, drug
      concentration, enhancers, and inhibitors. This model was also used to indicate
      the differences among Lac-NCTD, Lac-NCTD-associated chitosan NPs (Lac-NCTD-CS
      NPs), and Lac-NCTD-TMC- NPs in the absorption and transportation of membranes.
      Drug concentration levels were measured using high-performance liquid
      chromatography. Active transport and paracellular transport were suggested to be
      both the primary and secondary mechanisms for Lac-NCTD absorption, respectively.
      Lac-NCTD uptake and absorption were not controlled by pH levels, but were
      positively correlated to uptake time, and negatively correlated to temperature.
      The basolateral to apical apparent permeability coefficients (Papps) were higher
      than those of the apical to basolateral values. The inhibitor of P-glycoprotein
      and the multidrug resistance-associated protein 2 significantly enhanced the
      uptake amount of Lac-NCTD. Compared with Lac-NCTD, Lac-NCTD-CS-NPs and Lac-NCTD
      TMC-NPs significantly enhanced drug absorption. Additionally, the latter
      exhibited stronger action. Lac-NCTD-NPs could penetrate the plasma membrane of
      Caco-2 cells and translocate into the cytoplasm and even into the nucleus.
      Nanoparticles were uptaken into Caco-2 cells through the endocytosis pathway.

PMID- 22605940
TI  - Cancer treatment - objectives and quality of life issues.
AB  - The first aim of cancer treatment is to acheive a cure, and when cure is not
      possible, a good palliation (life prolongation and relief of sufferings) is
      warranted. This article highlights the aim of cancer treatment and also attempts
      to assess the issues of quality of life experienced as a result of the disease
      and its treatment. Palliative therapy should be less intensive than radical
      treatment and should cause less morbidity than disease itself. It must be
      effective, completed in a short time and should be tolerable. It is also
      essential for a physician to give a clear explanation of illness to the patient
      and realistic advice regarding the likely outcome of therapy and the long and
      short term morbidities which may occur. The patient may opt for a palliative
      treatment with a reduced chance of cure but a better quality of life than
      accepting a radical treatment with a potentially higher degree of morbidity.
      Quality of life in oncology practice should be seen as a process and as a part of
      this process it seems sensible to pursue several different lines of questionnaire
      development rather than constructing one 'perfect" quality of life instrument.

PMID- 22605941
TI  - Antitumour-promoting and cytotoxic constituents of etlingera elatior.
AB  - Phytochemical studies on rhizome of Etlingera elatior have resulted in the
      isolation of 1,7-bis(4-hydroxyphenyl)-2,4,6-heptatrienone (1), demethoxycurcumin
      (2), 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one (3), 16-hydroxylabda
      8(17),11,13-trien-16,15-olide (4), stigmast-4-en-3-one (5), stigmast-4-ene-3,6
      dione (6), stigmast-4-en-6b-ol-3-one (7), 5alpha,8alpha-epidioxyergosta-6,22-dien
      3beta-ol (8). 1 and 4 were new compounds. Compounds 5 and 7 displayed high
      antitumour-promoting activity. Ethyl acetate extract showed a very significant
      cytotoxic activity against CEM-SS and MCF-7 cell lines (4 MUg/ml and 6.25 MUg/ml
      respectively). The antitumour-promoting activity was determined by EBV-EA assay
      and cytotoxic activity was determined by MTT assay.

PMID- 22605942
TI  - Open label clinical trial to study adverse effects and tolerance to dry powder of
      the aerial part of andrographis paniculata in patients type 2 with diabetes
      mellitus.
AB  - Adverse effects and tolerance to dry powder of aerial part of Andrographis
      paniculata (Burm.f.) Nees were studied in 20 patients with type 2 diabetes
      mellitus for a period of 12 weeks. Patients were given powdered A. paniculata
      starting with 600 mg daily, gradually increasing to a maximum of 1.8 gm daily.
      Parameters monitored included body weight, blood pressure, liver function tests,
      renal function tests, cardiac enzymes, haemogram, serum electrolytes, fasting
      blood glucose, HbA1c, blood cholesterol, serum triglycerides and blood hormone
      levels (triiodotyronine, thyroxine, thyrotropin, insulin, fasting cortisol). None
      of the above mentioned parameters showed significant change during the study
      period except for a fall in HbA1c by 5.46% (p<0.01) and fasting S. insulin by
      20.93% (p<0.003). In conclusion, A. paniculata powder did not induced significant
      adverse events based on parameters observed in our study but significantly
      lowered HbA1c and fasting serum insulin in patients with type 2 diabetes.

PMID- 22605943
TI  - A Prelimenary Result of the Cardiovascular Risk factors Intervention Study (Pikom
      Study): Diabetes Mellitus, Hypertension and their Associated Factors.
AB  - Cardiovascular disease (CVD) has been the number one cause of death since the
      last three decades in Malaysia and diabetes mellitus and hypertension are
      considered as major risk factors. A study to reduce risk factors for
      cardiovascular diseases in the community (PIKOM) through education and lifestyle
      changes was undertaken. The study population was from four different areas in
      Peninsular Malaysia - Kota Bharu and Bachok in Kelantan ; Raub in Pahang; Gunung
      Besout in Perak and Felda Palong in Negri Sembilan. The subjects invited to
      participate in this study ware aged between 30 - 65 years, did not have any
      debilitating illnesses and no known history of diabetes mellitus, hypertension or
      cardiovascular disease. Subjects were asked to come to the local clinic in a
      fasting state and after physical examination, blood was taken for plasma glucose
      and lipids. Oral glucose tolerance test (OGTT) was then performed. A total of
      4,121 subjects participated in the study. The proportion of subjects with
      diabetes mellitus was highest in Felda Palong area (20.3%) and lowest in Raub
      area (7.1%). The proportion of subjects with hypertension was also highest in
      Felda Palong area (38.6%) and lowest in Raub area (29.1%). This could be
      attributable to the subjects in Felda Palong having the highest mean Body Mass
      Index (BMI) and Waist-to-Hip Ratio (WHR). There were significant associations
      between diabetes and hypertension with age and obesity. Subjects with diabetes
      mellitus and hypertension also had the highest mean age, BMI, WHR and plasma
      cholesterol.In conclusion, the proportion of patients with risk factors for CVD
      was high and intervention studies through education and lifestyle changes were
      being carried out to see their effectiveness.

PMID- 22605944
TI  - Students' perceptions of 'technology-based' lecture handouts.
AB  - Lecture handouts are widely used instructional tools. Handouts supplement rather
      than substitute students' regular reading. It is now a common practice to supply
      PowerPoint handouts and publish lecture handouts on the web for students' access.
      A study was conducted among the first year medical students (n=142) of School of
      Medical Sciences (SMS), Universiti Sains Malaysia (USM) in order to determine
      their perceptions and expectations with regards to lecture handouts provided to
      them. The majority of the students reported that they read the lecture handouts
      as a reference and found them useful as a guide for future learning. More than
      half (68%) of the students expressed dissatisfaction with the overall
      presentation format of the handouts which is mainly technology-related i.e.
      PowerPoint and photocopying. This study indicated that students' expectations and
      experiences were positive towards the use of handouts. They used handouts as a
      means of supplementing rather than substituting their learning. Much care is
      needed when educators supply computer-based handouts, as this study shows a
      number of limitations when students use them. Medical schools should consider
      publishing web-based handouts with online and other facilities to make it
      interesting and effective.

PMID- 22605945
TI  - The maxillary arch and its relationship to cephalometric landmarks of selected
      malay ethnic group.
AB  - The objectives of this study were to estimate the maxillary arch measurements, to
      assess the validity of Pont's & Korkhaus' Indices; to determine the relationship
      between maxillary arch form with head form; and to estimate the cephalic index
      (CI) of the study population. A cross-sectional study was conducted on 85 mature
      Malay students, 28 male students (32.98%), 57 females (67.02%) attending
      Teachers' Training College. Their mean age was 23.9 yr, and Cephalic Index (CI)
      86.4 (95% Confidence Interval 85.5-87.3). Arch and head dimensions were
      significantly larger in males than in females. CI was not significantly different
      between males and females. Means of anterior arch width (AAW), posterior-arch
      width (PAW) and arch-length (Lu) were 35.57mm, 47.3mm and 18.01mm respectively.
      They were significantly different from their corresponding Indices. Correlation
      Coefficient between bizygomatic width and anterior-arch-width was 0.18 and was
      not significant in both sexes of the present population.

PMID- 22605946
TI  - Incentive spirometry as a means to score breathlessness.
AB  - Perceived breathlessness played an important role in guiding treatment in asthma.
      We developed a simple, user-friendly method of scoring perception of dyspnoea
      (POD) using an incentive spirometer, Triflo II (Tyco Healthcare, Mansfield, USA)
      by means of repetitive inspiratory efforts achieved within three minutes in 175
      normal healthy subjects and 158 asthmatic patients of mild (n=26), moderate
      (n=78) and severe (n=54). Severity was stratified according to GINA guideline.
      The mean POD index in normal subjects, and asthmatic patients of mild, moderate
      and severe severity were: 6 (4-7) 16 (9-23), 25 (14-37), and 57 (14-100)
      respectively (p<0.001 One-Way ANOVA). Based on 17 asthmatic and 20 normal healthy
      subjects, intraclass correlation coefficients for POD index within subjects were
      high. In 14 asthmatic patients randomized to receiving nebulised b(2)-agonist or
      saline in a crossover, double-blind study, % FEV(1) change correlated with %
      changes in POD index [r(s) -0.46, p=0.012]. Finally, when compared with 6-minutes
      walking test (6MWT) in an open label study, respiratory POD index correlated with
      walking POD index in 21 asthmatic patients [r(s)= 0.58 (0.17 to 0.81) (p=0.007]
      and 26 normal subjects [0.50 (0.13 to 0.75) (p=0.008)]. We concluded that this
      test is discriminative between asthmatic patients of varying severity and from
      normal subjects, is reproducible, responsive to bronchodilator effect, and
      comparable with 6MWT. Taken together, it has the potential to score disability
      and POD in asthma effectively and simply.

PMID- 22605947
TI  - Serum leptin and corticosterone levels after exposure to noise stress in rats.
AB  - Even though extensive studies have been conducted on the effect of noise exposure
      on hearing apparatus / auditory system, information on the effect of noise on the
      other body functions is sparse. The present study examined the effect of exposure
      of albino rats to acute and chronic noise stress on two important interlaced
      endocrine levels. In acute experiments the animals were exposed to 120 dB noise
      for a duration of 1, 2, 3 hrs. In chronic experiments the animals were exposed to
      noise for one hour daily for 30, 60 and 90 days. Plasma corticosterone and leptin
      levels were measured in these animals. There was significant elevation in the
      levels of corticosterone and leptin after exposure to noise stress. The elevation
      in corticosterone level after noise stress is in agreement with earlier reports.
      So noise acts like a stressor and elevates the secretion of the corticosterone,
      the stress hormone and leptin, the product of the ob gene there is an elevation
      in leptin levels after noise stress.

PMID- 22605948
TI  - Anxiety, depression and psychosocial stress in patients with cardiac events.
AB  - Stress tends to worsen the prognosis of patients with coronary heart disease. The
      aim of the study is to determine the relationship between stress related
      psychosocial factors like anxiety, depression and life events and temporally
      cardiac events specified as acute myocardial infarction and unstable angina 65
      subjects with confirmed myocardial infarction or unstable angina were interviewed
      using 2 sets of questionnaire, the Hospital Anxiety and Depression Scale (HADS)
      and Life Changes Stress Test, a segment of the Rahe's Stress and Coping Inventory
      first at time of occurrence of their cardiac event and the second time was 6
      months later. Anxiety, depression and life events scores were calculated for both
      and recurrence of cardiac event for the 6 month duration was also recorded.
      Patients who had significant levels of depression and or life events were ten
      times more likely to have recurrence of cardiac events as compared to those
      without risk for either of these psychological symptoms. Anxiety, depression and
      stress levels are significantly increased after the onset of ischemic heart
      disease and could be contributing or predisposing factors for the recurrence of
      cardiac events for these patients.

PMID- 22605949
TI  - Gallium scan in diagnosing ocular sarcoidosis.
AB  - A 40-year-old man presented with floaters and painless progressive blurring of
      vision in the right eye for one month duration. Visual acuity in the right eye
      was 6/24. There was mild anterior chamber reaction and vitritis. The optic disc
      was swollen and elevated with presence of granulomatous lesion in the optic disc
      head. Blood investigations were unremarkable. Serum angiotensin converting enzyme
      (ACE) was normal and conjunctival biopsy showed presence of inflammatory cells. B
      Scan ultrasound revealed an echo-dense lesion in the optic nerve head. There was
      increased uptake of the right lacrimal gland and presence of 'Panda sign' with
      Gallium scan. A diagnosis of right ocular sarcoidosis was made base on the
      clinical features and Gallium scan.

PMID- 22605950
TI  - Actinomycosis of the knee.
AB  - We report a case of actinomycosis presenting as a knee swelling in a 34 year-old
      man. Knee actinomycosis poses a diagnosis challenge to clinicians as it is rare,
      often mimics knee tuberculosis and culture of the causative microbes is
      technically difficult. The classic microscopic appearance of this Gram-positive
      bacteria often forms the basis of diagnosis.

PMID- 22605951
TI  - Neurosciences in university sains malaysia; the way to go forward in malaysia
      with vision 2020.

PMID- 22605952
TI  - The Use of SNPs in Pharmacogenomics Studies.
AB  - Pharmacogenomics is the study of how genetic makeup determines the response to a
      therapeutic intervention. It has the potential to revolutionize the practice of
      medicine by individualisation of treatment through the use of novel diagnostic
      tools. This new science should reduce the trial-and-error approach to the choice
      of treatment and thereby limit the exposure of patients to drugs that are not
      effective or are toxic for them. Single Nucleotide Polymorphisms (SNPs) holds the
      key in defining the risk of an individual's susceptibility to various illnesses
      and response to drugs. There is an ongoing process of identifying the common,
      biologically relevant SNPs, in particular those that are associated with the risk
      of disease. The identification and characterization of large numbers of these
      SNPs are necessary before we can begin to use them extensively as genetic tools.
      As SNP allele frequencies vary considerably across human ethnic groups and
      populations, the SNP consortium has opted to use an ethnically diverse panel to
      maximize the chances of SNP discovery. Currently most studies are biased
      deliberately towards coding regions and the data generated from them therefore
      are unlikely to reflect the overall distribution of SNPs throughout the genome.
      The SNP consortium protocol was designed to identify SNPs without any bias
      towards these coding regions. Most pharmacogenomic studies were carried out in
      heterogeneous clinical trial populations, using case-control or cohort
      association study designs employing either candidate gene or Linkage
      disequilibrium (LD) mapping approaches. Concerns about the required patient
      sample sizes, the extent of LD, the number of SNPs needed in a map, the cost of
      genotyping SNPs, and the interpretation of results are some of the challenges
      that surround this field. While LD mapping is appealing in that it is an unbiased
      approach and allows a comprehensive genome-wide survey, the challenges and
      limitations are significant. An alternative such as the candidate gene approach
      does offer several advantages over LD mapping. Ultimately, as all human genes are
      discovered, the need for random SNP markers diminishes and gene-based SNP
      approaches will predominate. The challenges will then be to demonstrate
      convincing links between genetic variation and drug responses and to translate
      that information into useful pharmacogenomic tests.

PMID- 22605953
TI  - Evaluation of the Teratogenicity of Aqueous Extract of Labisia pumila var. alata
      in rats.
AB  - A dose range study to assess the teratogenic potential of aqueous extract of
      Labisia pumila var. alata (Kacip Fatimah) was conducted in rodents. The extract
      at doses of 0 (control), 2, 20, 200, 400, 1000 mg/kg/day were respectively
      administered by gavaging to 6 groups of pregnant Sprague Dawley rats from day 6
      through day 16 of pregnancy and sacrificed on day 21. No significant agent
      related effects including changes in maternal body weight (MBW) nor weight gain
      were observed. The corrected maternal body weights (CMBW) were slightly higher in
      animals receiving low dose extracts (2 mg/kg/day) as compared to all groups of
      animals. However, body weight differences were not statistically significant.
      Gravid uterine weight, number of corpora lutea, number of implantation sites,
      percentage of foetal resorptions, number of life foetuses, foetal weight and
      foetal sex ratio showed no significant differences among all group animals. None
      of the foetuses from all dams showed evidence of external congenital
      malformations. These findings may suggest that aqueous extracts of Labisia pumila
      var. alata up to 1000 mg/kg/day statistically do not show any significant
      teratogenic effects in rats but do affect the maternal body weight and this is
      dose dependent.

PMID- 22605954
TI  - In vitro effects of plantago major extract on urolithiasis.
AB  - The study was carried out to determine the in vitro effect of Plantago major
      extract on calcium oxalate crystals and to compare the effects of Plantago major
      extract with clinically used drugs like allopurinol and potassium citrate
      (positive controls). Modified Schneider slide gel method was used for the in
      vitro study and the crystals formed were measured by Image Analyser system KS
      300, 3.0 Carl Zeiss. The concentrations of Plantago major extract used were from
      100ppm to 350ppm. Plantago major extract at concentrations in the range of
      (100ppm-350ppm) significantly inhibited the size of calcium oxate crystals
      (dihydrate variety) against negative control (p<0.05) and against positive
      controls (p<0.05). However the inhibition concentration 50 (IC(50)) values on the
      size of calcium oxalate crystal for the extract, potassium citrate and
      allopurinol were 300ppm, 350ppm and 450ppm respectively. Extract of Plantago
      major also has inhibition effect on the number of crystals but it was not
      significant. In conclusion extract of Plantago major was better than allopurinol
      and potassium citrate in inhibiting the size of the calcium oxalate crystal in
      vitro.

PMID- 22605955
TI  - Absence of Ras, c-myc and Epidermal Growth Factor Receptor (EGFR) Mutations in
      Human Gliomas and its Clinical Factors Associated with Pathological Grading After
      Six Years of Diagnosis in North East Malaysian Patients.
AB  - Neoplastic transformation appears to be a multi-step process in which the normal
      controls of cell proliferation and cell-cell interaction are lost, thus
      transforming normal cells into cancer. The tumorigenic process involves the
      interplay between oncogenes and tumour suppressor genes. In this study, we have
      selected the ras family, c-myc and epidermal growth factor receptor (EGFR) genes
      to detect whether their abnormalities are associated with the expression and
      progression of glioma cases in Malay patients. We have used the polymerase chain
      reaction-single stranded conformation polymorphism followed by direct sequencing
      for the study. For the ras gene family, we screened the point mutations in codons
      12 and 61 of the H-, K-, and N-ras gene; for EGFR and c-myc, we analyzed only the
      exon 1 in glioma samples. In mutational screening analyses of the ras family, c
      myc and EGFR gene, there was no mobility shift observed in any tumour analyzed.
      All patterns of single stranded conformation polymorphism (SSCP) band observed in
      tumour samples were normal compared to those in normal samples. The DNA
      sequencing results in all high-grade tumours showed that all base sequences were
      normal. All 48 patients survived after five years of treatment. In simple
      logistic regression analysis, variables which were found to be significant were
      hemiplegia (p=0.047) and response radiotherapy (p=0.003). Hemiplegics were 25
      times more likely to have high pathological grade compared to those without.
      Patients with vascular involvement were 5.5 times more likely to have higher
      pathological grade. However, these findings were not significant in multivariate
      analysis. Patients who had radiotherapy were nearly 14 times more likely to have
      higher pathological grade. Multivariate analysis revealed that patients with
      hemiplegia were more likely to have higher pathological grade (p= 0.008). Those
      with higher pathological grading were 80 times more likely to have radiotherapy
      (p=0.004).

PMID- 22605956
TI  - Ambulance services at hospital universiti sains malaysia and hospital kota bharu:
      a retrospective study of calls.
AB  - This retrospective study attempted to identify the pattern of ambulance calls for
      the past two years at the Hospital Universiti Sains Malaysia (HUSM) and Hospital
      Kota Bharu (HKB). This study will provide a simple method of acquiring
      information related to ambulance response time (ART) and to test whether it met
      the international standards and needs of the client. Additionally, this paper
      takes into account the management of emergency calls. This included ambulance
      response time, which was part of Emergency Medical Services (EMS) episode: onset
      of ART, which started when details like phone number of the caller, exact
      location of the incident and the nature of the main complaint had been noted. ART
      ended when the emergency team arrived at the scene of incident. Information
      regarding ambulance calls from the record offices of HUSM and HKB was recorded
      for the year 2001 and 2002, tabulated and analyzed. There was a significant
      difference in the total number of calls managed by HUSM and HKB in the year 2001.
      It was noted that 645 calls were managed by HUSM while 1069 calls were recorded
      at HKB. In the year 2002, however, HUSM led with 613 extra numbers of calls as
      compare to HKB with 1193 numbers of calls. The pattern of ambulance calls
      observed is thought to possibly be influenced by social activities like local
      festivities, school holidays and the seasons. Further, it is observed that no
      studies were previously undertaken to compare the ART at both the HUSM and HKB to
      that of the international standards. In fact, a literature review undertaken so
      far showed no similar studies have been done for the whole Malaysia.

PMID- 22605957
TI  - Impact of a spreading epidemic on medical students.
AB  - The emergence of severe acute respiratory syndrome (SARS) had caused fear and
      anxiety of unprecedented proportion. To examine the impact of SARS on the medical
      students in a private medical university, a self-reporting questionnaire study
      was carried out to assess the factual knowledge, anxiety level and perception of
      the crisis, among the students. The two-week study (between 12 and 23 May, 2003)
      was carried out three weeks after the first reported SARS-related death in
      Malaysia. Ninety-one Phase I (junior) and 113 Phase II (senior) students
      completed the questionnaires. A large majority of students of Phase I and II were
      correct in their factual knowledge and were sensible in their perception of the
      future and the handling of the crisis by government(s). However, phase 1 students
      expressed significantly greater degree of anxiety compared to Phase II in
      relation to attendance and personal protection in hospital, and in meeting people
      coughing in public places. The lesser degree of anxiety expressed by phase II
      senior students may be due in part, to a more realistic assessment of SARS risk
      brought about by maturity, time spent in hospital and interaction with clinical
      lecturers and medical staff.

PMID- 22605958
TI  - Usage of traditional medicines among elderly and the prevalence of prednisolone
      contamination.
AB  - The elderly consume many medications including traditional medicines. In 1986, it
      was found that 29% of elderly took traditional medicines although in 1996, the
      National Health Morbidity survey reported a 2.3% prevalence. However, studies
      from other countries showed much higher percentages. The Ministry of Health in
      Malaysia is concerned that some of these preparations maybe contaminated with
      steroids, antihistamines, hormones and other poisons. The aims of the study were
      to determine a). the health seeking behaviour of elderly Malays living in rural
      areas, b). the utilization of both modern and traditional medicines and c). the
      steroid content of the traditional medicines used. Methodology included
      interviews using structured questionnaires of elderly Malays living in rural
      areas of Kelantan, aged above 60 years. Samples of traditional medications
      collected were sent to the Pharmacology Department, School of Medical Sciences,
      Universiti Sains Malaysia, for steroid content analysis using Thin Layer
      Chromatography. A total of 599 elderly respondents were interviewed comprising
      62.4% females and 37.6% males. The 60-69 years cohort group made up 48.7%,
      followed by 70-79 years at 36.1% and the remainder 15.2% were more than 80 years.
      There were 82% of elderly taking medicines. The trends of utilization of modern
      and traditional medicine in the last two weeks among elderly were 59.3% and 40.9%
      respectively. The utilization of traditional medicine by rural elderly Malays was
      therefore much higher than that reported in the previous study and nearly similar
      to that of France and Australian studies. There were 102 samples of traditional
      medications collected and analysed for steroid content. Results showed that 27.5%
      were positive for prednisolone, 34.3% positive for unknown steroids (a total of
      61.8%) and 38.2% were negative for both steroids. The present study therefore
      once again confirmed the high usage of traditional medicines where some of which
      are contaminated with steroids.

PMID- 22605959
TI  - The co-existence of pure red cell aplasia and autoimmune haemolytic anaemia in a
      child with malignant lymphoma.
AB  - The association between pure red cell aplasia (PRCA) and autoimmune haemolytic
      anaemia (AIHA) has rarely been reported. PRCA represents an isolated process,
      characterized by normochromic, normocytic anaemia, reticulocytopenia and
      erythroid hypoplasia in the bone marrow, and may be attributable to infection
      with Parvo virus B19. AIHA is a condition in which peripheral red blood cell
      destruction is induced by the presence of autoantibodies. However, the co
      existence of these conditions is very rare, since only few cases of PRCA and AIHA
      associated with malignant lymphoma (ML) were reported. A case of PRCA and AIHA
      was detected and described, for the first time in Malaysia, in a 10-year-old
      child suffering from non-Hodgkin lymphoma from the Department of Haematology,
      Universiti Sains Malaysia. Following the induction course of chemotherapy, the
      patient turned anaemic, with tendency for red cell clumping, reticulocytopenia
      and anisocytosis. AIHA was suspected in spite of the weak Coomb reaction
      obtained. The bone marrow aspirate revealed the presence of giant pronormoblasts,
      suggesting PRCA. Serological tests for Parvo virus and other viruses were
      negative.

PMID- 22605960
TI  - Extradural spinal schwannoma in 12 year old child : a case report.
AB  - We report a case of a 12 year old girl who presented with cord compression.
      Imaging studies demonstrated an extradural spinal tumour in the lower thoracic
      and upper lumbar levels. Histology confirmed the diagnosis of schwannoma while
      associated findings suggested the possibility of Neurofibromatosis Type I.

PMID- 22605961
TI  - Development of 16 microsatellite markers for Prince's Pine, Chimaphila japonica
      (Pyroleae, Monotropoideae, Ericaceae).
AB  - The perennial evergreen herb, Chimaphila japonica is found exclusively in East
      Asian temperate coniferous or sometimes in deciduous forests. By using the Fast
      Isolation by Amplified Fragment Length Polymorphism (AFLP) of Sequences
      Containing repeats (FIASCO) protocol, 20 microsatellite primer sets were
      identified in two wild populations. Of these primers, 16 displayed polymorphisms
      and 4 were monomorphic. The number of alleles per locus ranged from one to six
      among populations, values for expected and observed heterozygosities ranged from
      0.000 to 0.848 and from 0.000 to 1.000, respectively. The new SSR markers will be
      useful in obtaining estimates of population-level genetic diversity and in
      phylogeographic studies of C. japonica.

PMID- 22605962
TI  - Folate intake and methylenetetrahydrofolate reductase gene polymorphisms as
      predictive and prognostic biomarkers for ovarian cancer risk.
AB  - Folic acid and methylenetetrahydrofolate reductase (MTHFR) may affect the
      development of human cancer. However, few studies have evaluated folate intake
      and MTHFR in susceptibility to and prognosis of patients with ovarian cancer. We
      conducted a prospective case-control study in 215 ovarian cancer patients and 218
      controls (all Chinese) between Jan. 2004 and Jan. 2007. MTHFR C677T genotyping
      was done by PCR-RFLP. All patients were followed up until Dec. 2010. We found a
      2.43-fold increased risk of ovarian cancer among MTHFR 677TT carriers, and a
      decreased risk of ovarian cancer in individuals with high folate intake (OR =
      0.54, 95% CI = 0.32-0.94). Cox regression survival analysis showed that among the
      ovarian cancer patients, those carrying the 677TT genotype had a higher risk of
      death (HR = 2.17, 95% CI = 1.20-4.79), while high folate intake was associated
      with a lower risk of death (HR = 0.43, 95% CI = 0.33-0.88). Moreover, MTHFR 677CC
      carriers with higher folate intake showed a lower risk of death from ovarian
      cancer (HR = 0.32, 95% CI = 0.27-0.82). In summary, high folate intake may lessen
      susceptibility and improve the prognosis of ovarian cancer patients, while the
      MTHFR 677TT genotype appears to increase ovarian cancer risk and worsen its
      prognosis in a Chinese population.

PMID- 22605963
TI  - Isolation and purification of a novel deca-antifungal peptide from potato
      (Solanum tuberosum L. cv. Jopung) against Candida albicans.
AB  - In a previous study, an antifungal protein, AFP-J, was purified from tubers of
      the potato (Solanum tuberosum cv. L Jopung) and by gel filtration and HPLC. In
      this study, the functional peptide was characterized by partial acid digestion
      using HCl and HPLC. We obtained three peaks from the AFP-J, the first and third
      peaks were not active in the tested fungal strain. However, the second peak,
      which was named Potide-J, was active (MIC; 6.25 MUg/mL) against Candida albicans.
      The amino acid sequences were analyzed by automated Edman degradation, and the
      amino acid sequence of Potide-J was determined to be Ala-Val-Cys-Glu-Asn-Asp-Leu
      Asn-Cys-Cys. Mass spectrometry showed that its molecular mass was 1083.1 Da.
      Finally, we confirmed that a disulfide bond was present between Cys(3) and Cys(9)
      or Cys(10). Using this structure, Potide-J was synthesized via solid-phase
      methods. In these experiments, only the linear sequence was shown to display
      strong activity against Candida albicans. These results suggest that Potide-J may
      be an excellent candidate compound for the development of commercially applicable
      antibiotic agents.

PMID- 22605964
TI  - Classification of HCV NS5B polymerase inhibitors using support vector machine.
AB  - Using a support vector machine (SVM), three classification models were built to
      predict whether a compound is an active or weakly active inhibitor based on a
      dataset of 386 hepatitis C virus (HCV) NS5B polymerase NNIs (non-nucleoside
      analogue inhibitors) fitting into the pocket of the NNI III binding site. For
      each molecule, global descriptors, 2D and 3D property autocorrelation descriptors
      were calculated from the program ADRIANA.Code. Three models were developed with
      the combination of different types of descriptors. Model 2 based on 16 global and
      2D autocorrelation descriptors gave the highest prediction accuracy of 88.24% and
      MCC (Matthews correlation coefficient) of 0.789 on test set. Model 1 based on 13
      global descriptors showed the highest prediction accuracy of 86.25% and MCC of
      0.732 on external test set (including 80 compounds). Some molecular properties
      such as molecular shape descriptors (InertiaZ, InertiaX and Span), number of
      rotatable bonds (NRotBond), water solubility (LogS), and hydrogen bonding related
      descriptors performed important roles in the interactions between the ligand and
      NS5B polymerase.

PMID- 22605965
TI  - Possible time-dependent effect of ions and hydrophilic surfaces on the electrical
      conductivity of aqueous solutions.
AB  - The purpose of this work was to determine the influence of mechanical and
      electrical treatment on the electrical conductivity of aqueous solutions.
      Solutions were treated mechanically by iteration of two steps: 1:100 dilution and
      vigorous shaking. These two processes were repeated until extremely dilute
      solutions were obtained. For electrical treatment the solutions were exposed to
      strong electrical impulses. Effects of mechanical (as well as electrical)
      treatment could not be demonstrated using electrical conductivity measurements.
      However, significantly higher conductivity than those of the freshly prepared
      chemically analogous solutions was found in all aged solutions except for those
      samples stored frozen. The results surprisingly resemble a previously observed
      weak gel-like behavior in water stored in closed flasks. We suggest that ions and
      contact with hydrophilic glass surfaces could be the determinative conditions for
      the occurrence of this phenomenon.

PMID- 22605966
TI  - Elaeis oleifera genomic-SSR markers: exploitation in oil palm germplasm diversity
      and cross-amplification in arecaceae.
AB  - Species-specific simple sequence repeat (SSR) markers are favored for genetic
      studies and marker-assisted selection (MAS) breeding for oil palm genetic
      improvement. This report characterizes 20 SSR markers from an Elaeis oleifera
      genomic library (gSSR). Characterization of the repeat type in 2000 sequences
      revealed a high percentage of di-nucleotides (63.6%), followed by tri-nucleotides
      (24.2%). Primer pairs were successfully designed for 394 of the E. oleifera
      gSSRs. Subsequent analysis showed the ability of the 20 selected E. oleifera gSSR
      markers to reveal genetic diversity in the genus Elaeis. The average Polymorphism
      Information Content (PIC) value for the SSRs was 0.402, with the tri-repeats
      showing the highest average PIC (0.626). Low values of observed heterozygosity
      (H(o)) (0.164) and highly positive fixation indices (F(is)) in the E. oleifera
      germplasm collection, compared to the E. guineensis, indicated an excess of
      homozygosity in E. oleifera. The transferability of the markers to closely
      related palms, Elaeis guineensis, Cocos nucifera and ornamental palms is also
      reported. Sequencing the amplicons of three selected E. oleifera gSSRs across
      both species and palm taxa revealed variations in the repeat-units. The study
      showed the potential of E. oleifera gSSR markers to reveal genetic diversity in
      the genus Elaeis. The markers are also a valuable genetic resource for studying
      E. oleifera and other genus in the Arecaceae family.

PMID- 22605967
TI  - Response surface methodology to optimize enzymatic preparation of Deapio
      Platycodin D and Platycodin D from Radix Platycodi.
AB  - In the present work, we reported the enzymatic preparation of deapio-platycodin D
      (dPD) and platycodin D (PD) optimized by response surface methodology (RSM) from
      Radix Platycodi. During investigation of the hydrolysis of crude platycosides by
      various glycoside hydrolases, snailase showed a strong ability to transform
      deapio-platycoside E (dPE) and platycoside E (PE) into dPD and PD with 100%
      conversion. RSM was used to optimize the effects of the reaction temperature (35
      45  degrees C), enzyme load (5-20%), and reaction time (4-24 h) on the conversion
      process. Validation of the RSM model was verified by the good agreement between
      the experimental and the predicted values of dPD and PD conversion yield. The
      optimum preparation conditions were as follows: temperature, 43  degrees C;
      enzyme load, 15%; reaction time, 22 h. The biotransformation pathways were dPE
      >dPD3->dPD and PE->PD3->PD, respectively. The determined method may be highly
      applicable for the enzymatic preparation of dPD and PD for medicinal purposes and
      also for commercial use.

PMID- 22605968
TI  - Subminimal inhibitory concentrations of the disinfectant benzalkonium chloride
      select for a tolerant subpopulation of Escherichia coli with inheritable
      characteristics.
AB  - Exposure of Escherichia coli to a subminimal inhibitory concentration (25% below
      MIC) of benzalkonium chloride (BC), an antimicrobial membrane-active agent
      commonly used in medical and food-processing environments, resulted in cell death
      and changes in cell morphology (filamentation). A small subpopulation (1-5% of
      the initial population) survived and regained similar morphology and growth rate
      as non-exposed cells. This subpopulation maintained tolerance to BC after serial
      transfers in medium without BC. To withstand BC during regrowth the cells up
      regulated a drug efflux associated gene (the acrB gene, member of the AcrAB-TolC
      efflux system) and changed expression of outer membrane porin genes (ompFW) and
      several genes involved in protecting the cell from the osmotic- and oxidative
      stress. Cells pre-exposed to osmotic- and oxidative stress (sodium chloride,
      salicylic acid and methyl viologen) showed higher tolerance to BC. A control and
      two selected isolates showing increased BC-tolerance after regrowth in BC was
      genome sequenced. No common point mutations were found in the BC- isolates but
      one point mutation in gene rpsA (Ribosomal protein S1) was observed in one of the
      isolates. The observed tolerance can therefore not solely be explained by the
      observed point mutation. The results indicate that there are several different
      mechanisms responsible for the regrowth of a tolerant subpopulation in BC, both
      BC-specific and general stress responses, and that sub-MIC of BC may select for
      phenotypic variants in a sensitive E. coli culture.

PMID- 22605969
TI  - Antimicrobial, antiproliferative and proapoptotic activities of extract,
      fractions and isolated compounds from the stem of Erythroxylum caatingae plowman.
AB  - In the study, we have examined the antitumor and antimicrobial activities of the
      methanol extract, the fractions, a fraction of total alkaloids and two alkaloids
      isolated from the stem of Erythroxylum caatingae Plowman. All test fractions,
      except the hexane fractions, showed antimicrobial activity on gram-positive
      bacteria and fungi. The acetate: methanol (95:5), acetate, chloroform and hexane
      fractions show the highest cytotoxicity activity against the NCI-H292, HEp-2 and
      K562 cell lines using MTT. The absence of hemolysis in the erythrocytes of mice
      was observed in these fractions and 6beta-Benzoyloxy-3alpha-(3,4,5-
      trimethoxybenzoyloxy) tropane (catuabine B). Staining with Annexin V-FITC and JC
      1 was used to verify the mechanism of action of the compounds of E. caatingae
      that showed cytotoxicity less than 30 MUg/mL in leukemic cells. After 48 h of
      incubation, we observed that the acetate: methanol (95:5), acetate, and
      chloroform fractions, as well as the catuabine B, increased in the number of
      cells in early apoptosis, from 53.0 to 74.8%. An analysis of the potential of the
      mitochondrial membrane by incorporation of JC-1 showed that most cells during
      incubation of the acetate: methanol (95:5) and acetate fractions (63.85 and
      59.2%) were stained, suggesting the involvement of an intrinsic pathway of
      apoptosis.

PMID- 22605970
TI  - Comparison of ultrasonic and CO2laser pretreatment methods on enzyme
      digestibility of corn stover.
AB  - To decrease the cost of bioethanol production, biomass recalcitrance needs to be
      overcome so that the conversion of biomass to bioethanol becomes more efficient.
      CO(2) laser irradiation can disrupt the lignocellulosic physical structure and
      reduce the average size of fiber. Analyses with Fourier transform infrared
      spectroscopy, specific surface area, and the microstructure of corn stover were
      used to elucidate the enhancement mechanism of the pretreatment process by CO(2)
      laser irradiation. The present work demonstrated that the CO(2) laser had
      potential to enhance the bioconversion efficiency of lignocellulosic waste to
      renewable bioethanol. The saccharification rate of the CO(2) laser pretreatment
      was significantly higher than ultrasonic pretreatment, and reached 27.75% which
      was 1.34-fold of that of ultrasonic pretreatment. The results showed the impact
      of CO(2) laser pretreatment on corn stover to be more effective than ultrasonic
      pretreatment.

PMID- 22605971
TI  - Labeling of anti-MUC-1 binding single chain Fv fragments to surface modified
      upconversion nanoparticles for an initial in vivo molecular imaging proof of
      principle approach.
AB  - In vivo optical Imaging is an inexpensive and highly sensitive modality to
      investigate and follow up diseases like breast cancer. However, fluorescence
      labels and specific tracers are still works in progress to bring this promising
      modality into the clinical day-to-day use. In this study an anti-MUC-1 binding
      single-chain antibody fragment was screened, produced and afterwards labeled with
      newly designed and surface modified NaYF(4):Yb,Er upconversion nanoparticles as
      fluorescence reporter constructs. The MUC-1 binding of the conjugate was examined
      in vitro and in vivo using modified state-of-the-art small animal Imaging
      equipment. Binding of the newly generated upconversion nanoparticle based probe
      to MUC-1 positive cells was clearly shown via laser scanning microscopy and in an
      initial proof of principal small animal optical imaging approach.

PMID- 22605972
TI  - Congenital diarrheal disorders: an updated diagnostic approach.
AB  - Congenital diarrheal disorders (CDDs) are a group of inherited enteropathies with
      a typical onset early in the life. Infants with these disorders have frequently
      chronic diarrhea of sufficient severity to require parenteral nutrition. For most
      CDDs the disease-gene is known and molecular analysis may contribute to an
      unequivocal diagnosis. We review CDDs on the basis of the genetic defect,
      focusing on the significant contribution of molecular analysis in the complex,
      multistep diagnostic work-up.

PMID- 22605973
TI  - The relationship between grain hardness, dough mixing parameters and bread-making
      quality in winter wheat.
AB  - The influence of grain hardness, determined by using molecular markers and
      physical methods (near-infrared (NIR) technique and particle size index-PSI) on
      dough characteristics, which in turn were determined with the use of a
      farinograph and reomixer, as well as bread-making properties were studied. The
      material covered 24 winter wheat genotypes differing in grain hardness. The field
      experiment was conducted at standard and increased levels of nitrogen
      fertilization. Results of molecular analyses were in agreement with those
      obtained by the use of physical methods for soft-grained lines. Some lines
      classified as hard (by physical methods) appeared to have the wild-type Pina and
      Pinb alleles, similar to soft lines. Differences in dough and bread-making
      properties between lines classified as hard and soft on the basis of molecular
      data appeared to be of less significance than the differences between lines
      classified as hard and soft on the basis of physical analyses of grain texture.
      Values of relative grain hardness at the increased nitrogen fertilization level
      were significantly higher. At both fertilization levels the NIR parameter
      determining grain hardness was significantly positively correlated with the wet
      gluten and sedimentation values, with most of the rheological parameters and
      bread yield. Values of this parameter correlated with quality characteristics in
      a higher degree than values of particle size index.

PMID- 22605975
TI  - Carotenoids, fatty acid composition and heat stability of supercritical carbon
      dioxide-extracted-oleoresins.
AB  - The risk of chronic diseases has been shown to be inversely related to tomato
      intake and the lycopene levels in serum and tissue. Cis-isomers represent
      approximately 50%-80% of serum lycopene, while dietary lycopene maintains the
      isomeric ratio present in the plant sources with about 95% of all-trans-lycopene.
      Supercritical CO(2) extraction (S-CO(2)) has been extensively developed to
      extract lycopene from tomato and tomato processing wastes, for food or
      pharmaceutical industries, also by using additional plant sources as co-matrices.
      We compared two S-CO(2)-extracted oleoresins (from tomato and tomato/hazelnut
      matrices), which showed an oil-solid bi-phasic appearance, a higher cis-lycopene
      content, and enhanced antioxidant ability compared with the traditional solvent
      extracts. Heat-treating, in the range of 60-100  degrees C, led to changes in the
      lycopene isomeric composition and to enhanced antioxidant activity in both types
      of oleoresins. The greater stability has been related to peculiar lycopene isomer
      composition and to the lipid environment. The results indicate these oleoresins
      are a good source of potentially healthful lycopene.

PMID- 22605976
TI  - Pharmacological assessment of the medicinal potential of Acacia mearnsii De
      Wild.: antimicrobial and toxicity activities.
AB  - Acacia mearnsii De Wild. (Fabaceae) is a medicinal plant used in the treatment of
      microbial infections in South Africa without scientific validation of its
      bioactivity and toxicity. The antimicrobial activity of the crude acetone extract
      was evaluated by both agar diffusion and macrobroth dilution methods while its
      cytotoxicity effect was assessed with brine shrimp lethality assay. The study
      showed that both bacterial and fungal isolates were highly inhibited by the crude
      extract. The MIC values for the gram-positive bacteria (78.1-312.5) MUg/mL, gram
      negative bacteria (39.1-625) MUg/mL and fungal isolates (625-5000) MUg/mL differ
      significantly. The bacteria were more susceptible than the fungal strains tested.
      The antibiosis determination showed that the extract was more (75%) bactericidal
      than bacteriostatic (25%) and more fungicidal (66.67%) than fungistatic (33.33%).
      The cytotoxic activity of the extract was observed between 31.25 MUg/mL and 500
      MUg/mL and the LC(50) value (112.36 MUg/mL) indicates that the extract was
      nontoxic in the brine shrimp lethality assay (LC(50) > 100 MUg/mL). These results
      support the use of A. mearnsii in traditional medicine for treatment of microbial
      infections. The extract exhibiting significant broad spectrum antimicrobial
      activity and nontoxic effects has potential to yield active antimicrobial
      compounds.

PMID- 22605974
TI  - Scientific evidence and rationale for the development of curcumin and resveratrol
      as nutraceutricals for joint health.
AB  - Interleukin 1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) are key
      cytokines that drive the production of inflammatory mediators and matrix
      degrading enzymes in osteoarthritis (OA). These proinflammatory cytokines bind to
      their respective cell surface receptors and activate inflammatory signaling
      pathways culminating with the activation of nuclear factor kappaB (NF-kappaB), a
      transcription factor that can be triggered by a host of stress-related stimuli
      including, excessive mechanical stress and ECM degradation products. Once
      activated, NF-kappaB regulates the expression of many cytokines, chemokines,
      adhesion molecules, inflammatory mediators, and several matrix-degrading enzymes.
      Therefore, proinflammatory cytokines, their cell surface receptors, NF-kappaB and
      downstream signaling pathways are therapeutic targets in OA. This paper
      critically reviews the recent literature and outlines the potential prophylactic
      properties of plant-derived phytochemicals such as curcumin and resveratrol for
      targeting NF-kappaB signaling and inflammation in OA to determine whether these
      phytochemicals can be used as functional foods.

PMID- 22605977
TI  - CARD15/NOD2, CD14 and toll-like 4 receptor gene polymorphisms in Saudi patients
      with Crohn's Disease.
AB  - Crohn's disease (CD) is a multifactorial disease with a genetic component and an
      observed association with genes related to the innate immune response.
      Polymorphisms in the CARD15/NOD2 gene, in addition to functional variants of the
      toll-like receptor-4 (TLR4) and CD14 genes, have been associated with the
      development of Crohn's disease. There is no information about the frequency of
      these polymorphisms in the Saudi population. We examined the frequency of the
      three major CARD15/NOD2 risk alleles (Leu1007fsinsC, Arg702Trp, and Gly908Arg)
      and the TLR4 (Thr399Il) polymorphism as well as a functional polymorphism in the
      promoter of the CD14-159C/T in 46 Saudi CD patients and 50 matched controls.
      Genotyping was performed by allele-specific PCR or by restriction fragment length
      polymorphism (PCR-RFLP) analysis. The mutant genotype frequencies of the
      Leu1007fsinsC, Arg702Trp and Gly908Arg in the patient group were 6.5, 21.7 and
      6.5%, respectively, compared with frequencies of 0, 4 and 2%, respectively, in
      the control group. There were 15 patients who carried the mutant alleles for all
      three CARD15/NOD2 variants, Leu1007fsinsC, Arg702Trp and Gly908Arg, while none of
      the control candidates carried the three alleles. This genetic study provides
      evidence that the three major CARD15/NOD2 variant alleles and the CD14 -159C/T
      polymorphism are associated with Crohn's disease (CD) susceptibility in the Saudi
      population; however, there is no evidence that the TLR4 (Thr399Il) or CARD15/NOD2
      polymorphisms can be considered risk factors for Crohn's disease.

PMID- 22605978
TI  - Evolution of microsatellite Loci of tropical and temperate anguilla eels.
AB  - Anguilla eels are divided into temperate and tropical eels, based on their major
      distributions. The present study collected two temperate eels, Anguilla japonica
      and Anguilla anguilla, and two tropical eels, Anguilla marmorata and Anguilla
      bicolor pacifica, to examine two questions: do temperate and tropical Anguilla
      eels have different genetic polymorphic patterns?; and do temperate Anguilla
      japonica and Anguilla anguilla have a closer relationship to each other than to
      tropical eels? In total, 274 sequences were cloned and sequenced from six
      conserved microsatellite loci to examine polymorphic patterns of these four
      catadromous eels. Different mutational events, including substitutions, and
      repeat-unit deletions and insertions, appeared in major regions, while different
      point mutations were observed in flanking regions. The results implied that
      parallel patterns of microsatellite sequences occurred within both tropical and
      temperate freshwater eels. Consensus flanking sequences of six homologous loci
      from each of the four species were constructed. Genetic distances ranged from
      0.044 (Anguilla bicolor pacifica vs. Anguilla marmorata) to 0.061 (Anguilla
      marmorata vs. Anguilla anguilla). The tree topology suggests the hypothesis of
      Anguilla japonica and Anguilla anguilla being a sister group must be rejected.

PMID- 22605980
TI  - Toward the understanding of the metabolism of levodopa I. DFT investigation of
      the equilibrium geometries, acid-base properties and levodopa-water complexes.
AB  - Levodopa (LD) is used to increase dopamine level for treating Parkinson's
      disease. The major metabolism of LD to produce dopamine is decarboxylation. In
      order to understand the metabolism of LD; the electronic structure of levodopa
      was investigated at the Density Functional DFT/B3LYP level of theory using the 6
      311+G** basis set, in the gas phase and in solution. LD is not planar, with the
      amino acid side chain acting as a free rotator around several single bonds. The
      potential energy surface is broad and flat. Full geometry optimization enabled
      locating and identifying the global minimum on this Potential energy surface
      (PES). All possible protonation/deprotonation forms of LD were examined and
      analyzed. Protonation/deprotonation is local in nature, i.e., is not transmitted
      through the molecular framework. The isogyric protonation/deprotonation reactions
      seem to involve two subsequent steps: First, deprotonation, then rearrangement to
      form H-bonded structures, which is the origin of the extra stability of the
      deprotonated forms. Natural bond orbital (NBO) analysis of LD and its
      deprotonated forms reveals detailed information of bonding characteristics and
      interactions across the molecular framework. The effect of deprotonation on the
      donor-acceptor interaction across the molecular framework and within the two
      subsystems has also been examined. Attempts to mimic the complex formation of LD
      with water have been performed.

PMID- 22605981
TI  - Synthesis of zinc oxide nanoparticles and their effect on the compressive
      strength and setting time of self-compacted concrete paste as cementitious
      composites.
AB  - In the present study, the mechanical properties of self-compacting concrete were
      investigated after the addition of different amounts of ZnO nanoparticles. The
      zinc oxide nanoparticles, with an average particle size of about 30 nm, were
      synthesized and their properties studied with the help of a scanning electron
      microscope (SEM) and X-ray diffraction. The prepared nanoparticles were partially
      added to self-compacting concrete at different concentrations (0.05, 0.1, 0.2,
      0.5 and 1.0%), and the mechanical (flexural and split tensile) strength of the
      specimens measured after 7, 14, 21 and 28 days, respectively. The present results
      have shown that the ZnO nanoparticles were able to improve the flexural strength
      of self-compacting concrete. The increased ZnO content of more than 0.2% could
      increase the flexural strength, and the maximum flexural and split tensile
      strength was observed after the addition of 0.5% nanoparticles. Finally, ZnO
      nanoparticles could improve the pore structure of the self-compacted concrete and
      shift the distributed pores to harmless and less-harmful pores, while increasing
      mechanical strength.

PMID- 22605979
TI  - Salivary defense proteins: their network and role in innate and acquired oral
      immunity.
AB  - There are numerous defense proteins present in the saliva. Although some of these
      molecules are present in rather low concentrations, their effects are additive
      and/or synergistic, resulting in an efficient molecular defense network of the
      oral cavity. Moreover, local concentrations of these proteins near the mucosal
      surfaces (mucosal transudate), periodontal sulcus (gingival crevicular fluid) and
      oral wounds and ulcers (transudate) may be much greater, and in many cases
      reinforced by immune and/or inflammatory reactions of the oral mucosa. Some
      defense proteins, like salivary immunoglobulins and salivary chaperokine
      HSP70/HSPAs (70 kDa heat shock proteins), are involved in both innate and
      acquired immunity. Cationic peptides and other defense proteins like lysozyme,
      bactericidal/permeability increasing protein (BPI), BPI-like proteins, PLUNC
      (palate lung and nasal epithelial clone) proteins, salivary amylase, cystatins,
      prolin-rich proteins, mucins, peroxidases, statherin and others are primarily
      responsible for innate immunity. In this paper, this complex system and function
      of the salivary defense proteins will be reviewed.

PMID- 22605984
TI  - Fly ash porous material using geopolymerization process for high temperature
      exposure.
AB  - This paper presents the results of a study on the effect of temperature on
      geopolymers manufactured using pozzolanic materials (fly ash). In this paper, we
      report on our investigation of the performance of porous geopolymers made with
      fly ash after exposure to temperatures from 600  degrees C up to 1000  degrees C.
      The research methodology consisted of pozzolanic materials (fly ash) synthesized
      with a mixture of sodium hydroxide and sodium silicate solution as an alkaline
      activator. Foaming agent solution was added to geopolymer paste. The geopolymer
      paste samples were cured at 60  degrees C for one day and the geopolymers samples
      were sintered from 600  degrees C to 1000  degrees C to evaluate strength loss
      due to thermal damage. We also studied their phase formation and microstructure.
      The heated geopolymers samples were tested by compressive strength after three
      days. The results showed that the porous geopolymers exhibited strength increases
      after temperature exposure.

PMID- 22605982
TI  - Ultraviolet C irradiation induces different expression of cyclooxygenase 2 in NIH
      3T3 cells and A431 cells: the roles of COX-2 are different in various cell lines.
AB  - Ultraviolet C (UVC) is a DNA damage inducer, and 20 J/m(2) of UVC irradiation
      caused cell growth inhibition and induced cell death after exposure for 24-36 h.
      The growth of NIH 3T3 cells was significantly suppressed at 24 h after UVC
      irradiation whereas the proliferation of A431 cells was inhibited until 36 h
      after UVC irradiation. UVC irradiation increased COX-2 expression and such up
      regulation reached a maximum during 3-6 h in NIH 3T3 cells. In contrast, UVC
      induced COX-2 reached a maximum after 24-36 h in A431 cells. Measuring
      prostaglandin E2 (PGE2) level showed a biphasic profile that PGE2 release was
      rapidly elevated in 1-12 h after UVC irradiation and increased again at 24 h in
      both cell lines. Treatment with the selective COX-2 inhibitor, SC-791, during
      maximum expression of COX-2 induction, attenuated the UVC induced-growth
      inhibition in NIH 3T3 cells. In contrast, SC-791 treatment after UVC irradiation
      enhanced death of A431 cells. These data showed that the patterns of UVC-induced
      PGE2 secretion from NIH 3T3 cells and A431 cells were similar despite the
      differential profile in UVC-induced COX-2 up-regulation. Besides, COX-2 might
      play different roles in cellular response to UVC irradiation in various cell
      lines.

PMID- 22605985
TI  - High genetic diversity and low differentiation of Michelia coriacea
      (Magnoliaceae), a critically endangered endemic in Southeast Yunnan, China.
AB  - Michelia coriacea, a critically endangered tree, has a restricted and fragmented
      distribution in Southeast Yunnan Province, China. The genetic diversity, genetic
      structure and gene flow in the three extant populations of this species were
      detected by 10 inter-simple sequence repeat (ISSR) markers and 11 simple sequence
      repeat (SSR) markers. Examination of genetic diversity revealed that the species
      maintained a relatively high level of genetic diversity at the species level
      (percentage of polymorphic bands) PPB = 96.36% from ISSRs; PPL (percentage of
      polymorphic loci) = 95.56% from SSRs, despite several fragmental populations. Low
      levels of genetic differentiation among the populations of M. coriacea were
      detected by Nei's G(st) = 0.187 for ISSR and Wright's F(st) = 0.090 for SSR
      markers, which is further confirmed by Bayesian model-based STRUCTURE and PCoA
      analysis that could not reveal a clear separation between populations, although
      YKP was differentiated to other two populations by ISSR markers. Meanwhile, AMOVA
      analysis also indicated that 22.84% and 13.90% of genetic variation existed among
      populations for ISSRs and SSRs, respectively. The high level of genetic
      diversity, low genetic differentiation, and the population, structure imply that
      the fragmented habitat and the isolated population of M. coriacea may be due to
      recent over-exploitation. Conservation and management of M. coriacea should
      concentrate on maintaining the high level of genetic variability through both in
      and ex-situ conservation actions.

PMID- 22605983
TI  - Evaluation of the adenocarcinoma-associated gene AGR2 and the intestinal stem
      cell marker LGR5 as biomarkers in colorectal cancer.
AB  - We aim to estimate the diagnostic performances of anterior gradient homolog-2
      (AGR2) and Leucine-rich repeat-containing-G-protein-coupled receptor 5 (LGR5) in
      peripheral blood (PB) as mRNA biomarkers in colorectal cancer (CRC) and to
      explore their prognostic significance. Real-time PCR was used to analyze AGR2 and
      LGR5 in 54 stages I-IV CRC patients and 19 controls. Both mRNAs were
      significantly increased in PB from CRC patients compared to controls. The area
      under the receiver-operating characteristic curves were 0.722 (p = 0.006), 0.376
      (p = 0.123) and 0.767 (p = 0.001) for AGR2, LGR5 and combined AGR2/LGR5,
      respectively. The AGR2/LGR5 assay resulted in 67.4% sensitivity and 94.7%
      specificity. AGR2 correlated with pT3-pT4 and high-grade tumors. LGR5 correlated
      with metastasis, R2 resections and high-grade. The progression-free survival
      (PFS) of patients with high AGR2 was reduced (p = 0.037; HR, 2.32), also in the
      stage I-III subgroup (p = 0.046). LGR5 indicated a poor prognosis regarding both
      PFS (p = 0.007; HR, 1.013) and overall survival (p = 0.045; HR, 1.01). High
      AGR2/LGR5 was associated with poor PFS (p = 0.014; HR, 2.8) by multivariate
      analysis. Our findings indicate that the assessment of AGR2 and LGR5 in PB might
      reflect the presence of circulating tumor cells (CTC) and stem cell like CTC in
      CRC. Increased AGR2 and LGR5 are associated with poor outcomes.

PMID- 22605986
TI  - Isolation and characterization of twelve polymorphic microsatellite Loci for the
      cocoa mirid bug Sahlbergella singularis.
AB  - Mirids are the primary pests affecting cocoa production in Africa, but no genetic
      studies have been conducted on these insects. Here we report the isolation and
      characterization of 12 polymorphic microsatellite loci for Sahlbergella
      singularis. A microsatellite-enriched genomic DNA library was developed and
      screened to identify marker loci. Twelve polymorphic loci were identified by
      screening 28 individuals collected from one presumed population in cocoa
      plantations in Southern Cameroon. The number of alleles ranged from 5 to 25,
      whereas the observed and the expected heterozygosities ranged from 0.179 to 0.786
      and from 0.671 to 0.946, respectively. Tests showed significant deviations from
      HW equilibrium for four loci, but no linkage disequilibrium was detected at any
      of the loci. No cross-species amplification was observed in two other mirid pests
      in Africa.

PMID- 22605987
TI  - Density functional theory (DFT) study of triphenylamine-based dyes for their use
      as sensitizers in molecular photovoltaics.
AB  - In this work we studied three dyes which are proposed for potential photovoltaic
      applications and named Dye7, Dye7-2t and Dye7-3t. The Density Functional Theory
      (DFT) was utilized, using the M05-2X hybrid meta-GGA functional and the 6
      31+G(d,p) basis set. This level of calculation was used to find the optimized
      molecular structure and to predict the main molecular vibrations, the absorption
      and emission spectra, the molecular orbitals energies, dipole moment, isotropic
      polarizability and the chemical reactivity parameters that arise from Conceptual
      DFT. Also, the pK(a) values were calculated with the semi-empirical PM6 method.

PMID- 22605988
TI  - Expression of Transient Receptor Potential Vanilloid (TRPV) channels in different
      passages of articular chondrocytes.
AB  - Ion channels play important roles in chondrocyte mechanotransduction. The
      transient receptor potential vanilloid (TRPV) subfamily of ion channels consists
      of six members. TRPV1-4 are temperature sensitive calcium-permeable, relatively
      non-selective cation channels whereas TRPV5 and TRPV6 show high selectivity for
      calcium over other cations. In this study we investigated the effect of time in
      culture and passage number on the expression of TRPV4, TRPV5 and TRPV6 in
      articular chondrocytes isolated from equine metacarpophalangeal joints.
      Polyclonal antibodies raised against TRPV4, TRPV5 and TRPV6 were used to compare
      the expression of these channels in lysates from first expansion chondrocytes
      (P0) and cells from passages 1-3 (P1, P2 and P3) by western blotting. TRPV4,
      TRPV5 and TRPV6 were expressed in all passages examined. Immunohistochemistry and
      immunofluorescence confirmed the presence of these channels in sections of
      formalin fixed articular cartilage and monolayer cultures of methanol fixed P2
      chondrocytes. TRPV5 and TRPV6 were upregulated with time and passage in culture
      suggesting that a shift in the phenotype of the cells in monolayer culture alters
      the expression of these channels. In conclusion, several TRPV channels are likely
      to be involved in calcium signaling and homeostasis in chondrocytes.

PMID- 22605989
TI  - Genetic diversity and differentiation of Dendrocalamus membranaceus (Poaceae:
      Bambusoideae), a declining bamboo species in Yunnan, China, as based on Inter
      Simple Sequence Repeat (ISSR) Analysis.
AB  - Dendrocalamus membranaceus Munro is a woody bamboo with a high economic and
      ecological value that often occurs as natural stands, such as in the large-scale
      forested areas of China's Yunnan Province. Due to its overexploitation, the
      habitat of D. membranaceus in Yunnan has been dramatically reduced, and the
      quality of the stands has declined. As a preliminary analysis in considering the
      effective protection for these germplasm resources, we assessed the genetic
      diversity of 12 natural populations in Yunnan, using inter-simple sequence repeat
      (ISSR) markers. From 10 ISSR primers, we generated 155 bands, of which 153 were
      polymorphic (98.71%). Compared with other species in the genus, this species
      demonstrated a greater genetic diversity (S = 0.349) and lower genetic
      differentiation (G(ST) = 0.252). Our analysis of molecular variance revealed that
      the genetic differentiation among the populations is significant. A large
      proportion of the genetic variation (78.95%) resides among the individuals within
      populations, whereas only 21.05% are found among populations. Mantel tests
      indicated no significant correlation between genetic and geographic distances
      among the populations. Given the low sexual reproducibility and characteristics
      of monocarpic plants, we recommend implementing in situ conservation measures for
      all of the D. membranaceus populations in Yunnan and collecting sufficient
      samples for ex situ conservation. Furthermore, the conservation area should be
      extended to its main natural habitats, the Lancang-Mekong River Valley.

PMID- 22605991
TI  - Biochemistry of bacterial multidrug efflux pumps.
AB  - Bacterial pathogens that are multi-drug resistant compromise the effectiveness of
      treatment when they are the causative agents of infectious disease. These multi
      drug resistance mechanisms allow bacteria to survive in the presence of
      clinically useful antimicrobial agents, thus reducing the efficacy of
      chemotherapy towards infectious disease. Importantly, active multi-drug efflux is
      a major mechanism for bacterial pathogen drug resistance. Therefore, because of
      their overwhelming presence in bacterial pathogens, these active multi-drug
      efflux mechanisms remain a major area of intense study, so that ultimately
      measures may be discovered to inhibit these active multi-drug efflux pumps.

PMID- 22605992
TI  - Combining molecular docking and molecular dynamics to predict the binding modes
      of flavonoid derivatives with the neuraminidase of the 2009 H1N1 influenza A
      virus.
AB  - Control of flavonoid derivatives inhibitors release through the inhibition of
      neuraminidase has been identified as a potential target for the treatment of H1N1
      influenza disease. We have employed molecular dynamics simulation techniques to
      optimize the 2009 H1N1 influenza neuraminidase X-ray crystal structure. Molecular
      docking of the compounds revealed the possible binding mode. Our molecular
      dynamics simulations combined with the solvated interaction energies technique
      was applied to predict the docking models of the inhibitors in the binding pocket
      of the H1N1 influenza neuraminidase. In the simulations, the correlation of the
      predicted and experimental binding free energies of all 20 flavonoid derivatives
      inhibitors is satisfactory, as indicated by R(2) = 0.75.

PMID- 22605990
TI  - The ascorbate-glutathione-alpha-tocopherol triad in abiotic stress response.
AB  - The life of any living organism can be defined as a hurdle due to different kind
      of stresses. As with all living organisms, plants are exposed to various abiotic
      stresses, such as drought, salinity, extreme temperatures and chemical toxicity.
      These primary stresses are often interconnected, and lead to the overproduction
      of reactive oxygen species (ROS) in plants, which are highly reactive and toxic
      and cause damage to proteins, lipids, carbohydrates and DNA, which ultimately
      results in oxidative stress. Stress-induced ROS accumulation is counteracted by
      enzymatic antioxidant systems and non-enzymatic low molecular weight metabolites,
      such as ascorbate, glutathione and alpha-tocopherol. The above mentioned low
      molecular weight antioxidants are also capable of chelating metal ions, reducing
      thus their catalytic activity to form ROS and also scavenge them. Hence, in plant
      cells, this triad of low molecular weight antioxidants (ascorbate, glutathione
      and alpha-tocopherol) form an important part of abiotic stress response. In this
      work we are presenting a review of abiotic stress responses connected to these
      antioxidants.

PMID- 22605993
TI  - Enhancement of mechanical and thermal properties of polycaprolactone/chitosan
      blend by calcium carbonate nanoparticles.
AB  - This study investigates the effects of calcium carbonate (CaCO(3)) nanoparticles
      on the mechanical and thermal properties and surface morphology of
      polycaprolactone (PCL)/chitosan nanocomposites. The nanocomposites of
      PCL/chitosan/CaCO(3) were prepared using a melt blending technique. Transmission
      electron microscopy (TEM) results indicate the average size of nanoparticles to
      be approximately 62 nm. Tensile measurement results show an increase in the
      tensile modulus with CaCO(3) nanoparticle loading. Tensile strength and
      elongation at break show gradual improvement with the addition of up to 1 wt% of
      nano-sized CaCO(3). Decreasing performance of these properties is observed for
      loading of more than 1 wt% of nano-sized CaCO(3). The thermal stability was best
      enhanced at 1 wt% of CaCO(3) nanoparticle loading. The fractured surface
      morphology of the PCL/chitosan blend becomes more stretched and homogeneous in
      PCL/chitosan/CaCO(3) nanocomposite. TEM micrograph displays good dispersion of
      CaCO(3) at lower nanoparticle loading within the matrix.

PMID- 22605994
TI  - Extreme multiple reticulate origins of the Pteris cadieri complex (Pteridaceae).
AB  - The Pteris cadieri complex displays extensive morphological variation and seems
      to have originated through hybridization. However, the members of this complex
      reproduce by apogamy, which usually limits genetic variation. To evaluate the
      hypotheses of hybrid origins, the pattern of evolution in this species complex is
      reconstructed. Multiple methodologies were used. Diploids, triploids, and
      tetraploids were identified by chromosome counts and flow cytometry. Nuclear DNA
      markers (cytosolic phosphoglucose isomerase gene, PgiC) were used, together with
      chloroplast DNA markers (atpB-rbcL spacer and rbcL gene) to infer the biparental
      and maternal lineages of the Pteris cadieri complex. The three cpDNA haplotype
      groups and five PgiC alleles found in this study indicate that the evolution of
      the Pteris cadieri complex has been extremely reticulate. Up to 11 taxa belonging
      to eight morphs were identified. By comparing genetic variation in the Pteris
      cadieri in two independent areas, Hainan and Taiwan, we inferred that
      hybridization has occurred independently in different areas. Furthermore, we
      found evidence for phenological divergence (evergreen and deciduous) within
      Taiwan. We propose that the Pteris cadieri complex originated from different
      genetic lineages through multiple hybridizations in different geographical areas,
      leading to its present morphological diversity.

PMID- 22605995
TI  - Identification of novel potential beta-N-acetyl-D-hexosaminidase inhibitors by
      virtual screening, molecular dynamics simulation and MM-PBSA calculations.
AB  - Chitinolytic beta-N-acetyl-d-hexosaminidases, as a class of chitin hydrolysis
      enzyme in insects, are a potential species-specific target for developing
      environmentally-friendly pesticides. Until now, pesticides targeting chitinolytic
      beta-N-acetyl-d-hexosaminidase have not been developed. This study demonstrates a
      combination of different theoretical methods for investigating the key structural
      features of this enzyme responsible for pesticide inhibition, thus allowing for
      the discovery of novel small molecule inhibitors. Firstly, based on the currently
      reported crystal structure of this protein (OfHex1.pdb), we conducted a pre
      screening of a drug-like compound database with 8 * 10(6) compounds by using the
      expanded pesticide-likeness criteria, followed by docking-based screening,
      obtaining 5 top-ranked compounds with favorable docking conformation into OfHex1.
      Secondly, molecular docking and molecular dynamics simulations are performed for
      the five complexes and demonstrate that one main hydrophobic pocket formed by
      residues Trp424, Trp448 and Trp524, which is significant for stabilization of the
      ligand-receptor complex, and key residues Asp477 and Trp490, are respectively
      responsible for forming hydrogen-bonding and pi-pi stacking interactions with the
      ligands. Finally, the molecular mechanics Poisson-Boltzmann surface area (MM
      PBSA) analysis indicates that van der Waals interactions are the main driving
      force for the inhibitor binding that agrees with the fact that the binding pocket
      of OfHex1 is mainly composed of hydrophobic residues. These results suggest that
      screening the ZINC database can maximize the identification of potential OfHex1
      inhibitors and the computational protocol will be valuable for screening
      potential inhibitors of the binding mode, which is useful for the future rational
      design of novel, potent OfHex1-specific pesticides.

PMID- 22605997
TI  - Effect of maturity on phenolics (phenolic acids and flavonoids) profile of
      strawberry cultivars and mulberry species from Pakistan.
AB  - In this study, we investigated how the extent of ripeness affects the yield of
      extract, total phenolics, total flavonoids, individual flavonols and phenolic
      acids in strawberry and mulberry cultivars from Pakistan. In strawberry, the
      yield of extract (%), total phenolics (TPC) and total flavonoids (TFC) ranged
      from 8.5-53.3%, 491-1884 mg gallic acid equivalents (GAE)/100 g DW and 83-327 mg
      catechin equivalents (CE)/100 g DW, respectively. For the different species of
      mulberry the yield of extract (%), total phenolics and total flavonoids of 6.9
      54.0%, 201-2287 mg GAE/100 g DW and 110-1021 mg CE/100 g DW, respectively, varied
      significantly as fruit maturity progressed. The amounts of individual flavonols
      and phenolic acid in selected berry fruits were analyzed by RP-HPLC. Among the
      flavonols, the content of myricetin was found to be high in Morus alba (88 mg/100
      g DW), the amount of quercetin as high in Morus laevigata (145 mg/100 g DW) while
      kaempferol was highest in the Korona strawberry (98 mg/100 g DW) at fully ripened
      stage. Of the six phenolic acids detected, p-hydroxybenzoic and p-coumaric acid
      were the major compounds in the strawberry. M. laevigata and M. nigra contained p
      coumaric acid and vanillic acid while M. macroura and M. alba contained p-hydroxy
      benzoic acid and chlorogenic acid as the major phenolic acids. Overall, a trend
      to an increase in the percentage of extraction yield, TPC, TFC, flavonols and
      phenolic acids was observed as maturity progressed from un-ripened to fully
      ripened stages.

PMID- 22605998
TI  - Characterization of high-value bioactives in some selected varieties of Pakistani
      Rice (Oryza sativa L.).
AB  - The present study reports the composition and variation of fatty acids, sterols,
      tocopherols and gamma-oryzanol among selected varieties namely Basmati Super,
      Basmati 515, Basmati 198, Basmati 385, Basmati 2000, Basmati 370, Basmati Pak,
      KSK-139, KS-282 and Irri-6 of Pakistani rice (Oryza sativa L). Oil content
      extracted with n-hexane from different varieties of brown rice seed (unpolished
      rice) ranged from 1.92% to 2.72%. Total fatty acid contents among rice varieties
      tested varied between 18240 and 25840 mg/kg brown rice seed. The rice tested
      mainly contained oleic (6841-10952 mg/kg) linoleic (5453-7874 mg/kg) and palmitic
      acid (3613-5489 mg/kg). The amounts of total phytosterols (GC and GC-MS
      analysis), with main contribution from beta-sitosterol (445-656 mg/kg),
      campesterol (116-242 mg/kg), Delta(5)-avenasterol (89-178 mg/kg) and stigmasterol
      (75-180 mg/kg) were established to be 739.4 to 1330.4 mg/kg rice seed. The
      content of alpha-, gamma- and delta-tocopherols as analyzed by HPLC varied from
      39.0-76.1, 21.6-28.1 and 6.5-16.5 mg/kg rice seed, respectively. The amounts of
      different gamma-oryzanol components (HPLC data), identified as cycloartenyl
      ferulate, 24-methylene cycloartanyl ferulate, campesteryl ferulate and beta
      sitosteryl ferulate, were in the range of 65.5-103.6, 140.2-183.1, 29.8-45.5 and
      8.6-10.4 mg/kg rice seed, respectively. Overall, the concentration of these
      bioactives was higher in the Basmati rice cultivars showing their functional food
      superiority. In conclusion, the tested varieties of Pakistani rice, especially
      the Basmati cultivars, can provide best ingredients for functional foods.

PMID- 22605999
TI  - Optical properties of bismuth tellurite based glass.
AB  - A series of binary tellurite based glasses (Bi(2)O(3))(x) (TeO(2))(100-) (x) was
      prepared by melt quenching method. The density, molar volume and refractive index
      increase when bismuth ions Bi(3+) increase, this is due to the increased
      polarization of the ions Bi(3+) and the enhanced formation of non-bridging oxygen
      (NBO). The Fourier transform infrared spectroscopy (FTIR) results show the
      bonding of the glass sample and the optical band gap, E(opt) decreases while the
      refractive index increases when the ion Bi(3+) content increases.

PMID- 22606000
TI  - Preparation and elastic moduli of germanate glass containing lead and bismuth.
AB  - This paper reports the rapid melt quenching technique preparation for the new
      family of bismuth-lead germanate glass (BPG) systems in the form of (GeO(2))(60)
      (PbO)(40-) (x)-(1/2Bi(2)O(3))(x) where x = 0 to 40 mol%. Their densities with
      respect of Bi(2)O(3) concentration were determined using Archimedes' method with
      acetone as a floatation medium. The current experimental data are compared with
      those of bismuth lead borate (B(2)O(3))(20)-(PbO)(80-) (x)-(Bi(2)O(3))(x). The
      elastic properties of BPG were studied using the ultrasonic pulse-echo technique
      where both longitudinal and transverse sound wave velocities have been measured
      in each glass samples at a frequency of 15 MHz and at room temperature.
      Experimental data shows that all the physical parameters of BPG including density
      and molar volume, both longitudinal and transverse velocities increase linearly
      with increasing of Bi(2)O(3) content in the germanate glass network. Their
      elastic moduli such as longitudinal, shear and Young's also increase linearly
      with addition of Bi(2)O(3) but the bulk modulus did not. The Poisson's ratio and
      fractal dimensionality are also found to vary linearly with the Bi(2)O(3)
      concentration.

PMID- 22605996
TI  - Cell adhesion and its endocytic regulation in cell migration during neural
      development and cancer metastasis.
AB  - Cell migration is a crucial event for tissue organization during development, and
      its dysregulation leads to several diseases, including cancer. Cells exhibit
      various types of migration, such as single mesenchymal or amoeboid migration,
      collective migration and scaffold cell-dependent migration. The migration
      properties are partly dictated by cell adhesion and its endocytic regulation.
      While an epithelial-mesenchymal transition (EMT)-mediated mesenchymal cell
      migration requires the endocytic recycling of integrin-mediated adhesions after
      the disruption of cell-cell adhesions, an amoeboid migration is not dependent on
      any adhesions to extracellular matrix (ECM) or neighboring cells. In contrast, a
      collective migration is mediated by both cell-cell and cell-ECM adhesions, and a
      scaffold cell-dependent migration is regulated by the endocytosis and recycling
      of cell-cell adhesion molecules. Although some invasive carcinoma cells exhibit
      an EMT-mediated mesenchymal or amoeboid migration, other cancer cells are known
      to maintain cadherin-based cell-cell adhesions and epithelial morphology during
      metastasis. On the other hand, a scaffold cell-dependent migration is mainly
      utilized by migrating neurons in normal developing brains. This review will
      summarize the structures of cell adhesions, including adherens junctions and
      focal adhesions, and discuss the regulatory mechanisms for the dynamic behavior
      of cell adhesions by endocytic pathways in cell migration in physiological and
      pathological conditions, focusing particularly on neural development and cancer
      metastasis.

PMID- 22606001
TI  - Salivary proteins associated with periodontitis in patients with Type 2 diabetes
      mellitus.
AB  - The objective of this study was to investigate the salivary proteins that are
      associated with periodontitis in patients with Type 2 diabetes mellitus (T2DM).
      Volunteers for the study were patients from the Diabetic Unit, University of
      Malaya Medical Centre, whose periodontal status was determined. The diabetic
      volunteers were divided into two groups, i.e., patients with periodontitis and
      those who were periodontally healthy. Saliva samples were collected and treated
      with 10% TCA/acetone/20 mM DTT to precipitate the proteins, which were then
      separated using two-dimensional polyacrylamide gel electrophoresis. Gel images
      were scanned using the GS-800(TM) Calibrated Densitometer. The protein spots were
      analyzed and expressed in percentage volumes. The percentage volume of each
      protein spot was subjected to Mann-Whitney statistical analysis using SPSS
      software and false discovery rate correction. When the expression of the salivary
      proteins was compared between the T2DM patients with periodontitis with those who
      were periodontally healthy, seven proteins, including polymeric immunoglobulin
      receptor, plastin-2, actin related protein 3, leukocyte elastase inhibitor,
      carbonic anhydrases 6, immunoglobulin J and interleukin-1 receptor antagonist,
      were found to be differentially expressed (p < 0.01304). This implies that the
      proteins may have the potential to be used as biomarkers for the prediction of
      T2DM patients who may be prone to periodontitis.

PMID- 22606002
TI  - Injurious effects of curcumin on maturation of mouse oocytes, fertilization and
      fetal development via apoptosis.
AB  - Curcumin, a common dietary pigment and spice, is a hydrophobic polyphenol derived
      from the rhizome of the herb Curcuma longa. Previously, we reported a cytotoxic
      effect of curcumin on mouse embryonic stem cells and blastocysts and its
      association with defects in subsequent development. In the present study, we
      further investigated the effects of curcumin on oocyte maturation and subsequent
      pre- and post-implantation development, both in vitro and in vivo. Notably,
      curcumin induced a significant reduction in the rate of oocyte maturation,
      fertilization, and in vitro embryonic development. Treatment of oocytes with
      curcumin during in vitro maturation (IVM) led to increased resorption of
      postimplantation embryos and decreased fetal weight. Experiments with an in vivo
      mouse model disclosed that consumption of drinking water containing 40 MUM
      curcumin led to decreased oocyte maturation and in vitro fertilization as well as
      early embryonic developmental injury. Finally, pretreatment with a caspase-3
      specific inhibitor effectively prevented curcumin-triggered injury effects,
      suggesting that embryo impairment by curcumin occurs mainly via a caspase
      dependent apoptotic process.

PMID- 22606003
TI  - Comparative study of essential oils extracted from Algerian Myrtus communis L.
      leaves using microwaves and hydrodistillation.
AB  - Two different extraction methods were used for a comparative study of algerian
      myrtle leaf essential oils: solvent-free-microwave-extraction (SFME) and
      conventional hydrodistillation (HD). Essential oils analyzed by GC and GC-MS
      presented 51 components constituting 97.71 and 97.39% of the total oils,
      respectively. Solvent-Free-Microwave-Extract Essential oils SFME-EO were richer
      in oxygenated compounds. Their major compounds were 1,8-cineole, followed by
      alpha-pinene as against alpha-pinene, followed by 1,8-cineole for HD. Their
      antimicrobial activity was investigated on 12 microorganisms. The antioxidant
      activities were studied with the 2,2-diphenyl-1-picrylhydrazyl (DPPH(*)) radical
      scavenging method. Generally, both essential oils showed high antimicrobial and
      weak antioxidant activities. Microstructure analyses were also undertaken on the
      solid residue of myrtle leaves by Scanning Electronic Microscopy (SEM); it showed
      that the SFME-cellular structure undergoes significant modifications compared to
      the conventional HD residual solid. Comparison between hydrodistillation and SFME
      presented numerous distinctions. Several advantages with SFME were observed:
      faster kinetics and higher efficiency with similar yields: 0.32% dry basis, in 30
      min as against 180 min for HD.

PMID- 22606004
TI  - Improved synthesis of 5-substituted 1H-tetrazoles via the [3+2] cycloaddition of
      nitriles and sodium azide catalyzed by silica sulfuric acid.
AB  - A silica supported sulfuric acid catalyzed [3+2] cycloaddition of nitriles and
      sodium azide to form 5-substituted 1H-tetrazoles is described. The protocol can
      provide a series of 5-substituted 1H-tetrazoles using silica sulfuric acid from
      nitriles and sodium azide in DMF in 72%-95% yield.

PMID- 22606005
TI  - Effect of calcium sprays on mechanical strength and cell wall fractions of
      herbaceous peony (Paeonia lactiflora pall.) inflorescence stems.
AB  - Calcium is an essential element and imparts significant structural rigidity to
      the plant cell walls, which provide the main mechanical support to the entire
      plant. In order to increase the mechanical strength of the inflorescence stems of
      herbaceous peony, the stems are treated with calcium chloride. The results shows
      that preharvest sprays with 4% (w/v) calcium chloride three times after bud
      emergence are the best at strengthening "Da Fugui" peonies' stems. Calcium sprays
      increased the concentrations of endogenous calcium, total pectin content as well
      as cell wall fractions in herbaceous peonies stems, and significantly increased
      the contents of them in the top segment. Correlation analysis showed that the
      breaking force of the top segment of peonies' stems was positively correlated
      with the ratio of water insoluble pectin to water soluble pectin (R = 0.673) as
      well as lignin contents (R = 0.926) after calcium applications.

PMID- 22606006
TI  - Frequent gene amplification predicts poor prognosis in gastric cancer.
AB  - Gastric cancer is one of the most common malignancies worldwide. However, genetic
      alterations leading to this disease are largely unknown. Gene amplification is
      one of the most frequent genetic alterations, which is believed to play a major
      role in the development and progression of gastric cancer. In the present study,
      we identified three frequently amplified genes from 30 candidate genes using real
      time quantitative PCR method, including ERBB4, C-MET and CD44, and further
      explored their association with clinicopathological characteristics and poor
      survival in a cohort of gastric cancers. Our data showed amplification of these
      genes was significantly associated with certain clinicopathological
      characteristics, particularly tumor differentiation and cancer-related death.
      More importantly, amplification of these genes was significantly related to worse
      survival, suggesting that these amplified genes may be significant predictors of
      poor prognosis and potential therapeutic targets in gastric cancer. Targeting
      these genes may thus provide new possibilities in the treatment of gastric
      cancer.

PMID- 22606009
TI  - An efficient intergeneric conjugation of DNA from Escherichia coli to mycelia of
      the lincomycin-producer Streptomyces lincolnensis.
AB  - Streptomyces lincolnensis is a producer of lincomycin, which is a lincosamide
      antibiotic for the treatment of infective diseases caused by Gram-positive
      bacteria. S. lincolnensis is refractory to introducing plasmid DNA into cells
      because of resistance of foreign DNAs and poor sporulation. In this study, a
      simple and efficient method of transferring plasmids into S. lincolnensis through
      the intergeneric Escherichia coli-mycelia conjugation was established and
      optimized for the first time. The recipient mycelia of S. lincolnensis were
      prepared in liquid SM medium containing 10.3% sucrose for three days. The
      dispersed mycelia were conjugated with competent E. coli donor cells. The
      exconjugants were regenerated efficiently on solid mannitol soya flour (MS)
      medium containing 20 mM MgCl(2). The average conjugation frequency was observed
      at 1.1 * 10(-4) per input donor cell and validated functionally by transferring
      two types of vectors containing lincomycin resistance genes lmrA, lmrB and lmrC
      into S. lincolnensis mycelia. The data of fermentation in shaking flasks showed
      the lincomycin yield of the exconjugants increased by 52.9% for the multiple copy
      vector and 38.3% for the integrative one, compared with the parental strain. The
      efficient and convenient method of intergeneric E. coli-mycelia conjugation in
      this study provides a promising procedure to introduce plasmid DNA into other
      refractory streptomycetes.

PMID- 22606010
TI  - Structural features of caspase-activating complexes.
AB  - Apoptosis, also called programmed cell death, is an orderly cellular suicide
      program that is critical for the development, immune regulation and homeostasis
      of a multi-cellular organism. Failure to control this process can lead to serious
      human diseases, including many types of cancer, neurodegenerative diseases, and
      autoimmununity. The process of apoptosis is mediated by the sequential activation
      of caspases, which are cysteine proteases. Initiator caspases, such as caspase-2,
      -8, -9, and -10, are activated by formation of caspase-activating complexes,
      which function as a platform to recruit caspases, providing proximity for self
      activation. Well-known initiator caspase-activating complexes include (1) DISC
      (Death Inducing Signaling Complex), which activates caspases-8 and 10; (2)
      Apoptosome, which activates caspase-9; and (3) PIDDosome, which activates caspase
      2. Because of the fundamental biological importance of capases, many structural
      and biochemical studies to understand the molecular basis of assembly mechanism
      of caspase-activating complexes have been performed. In this review, we summarize
      previous studies that have examined the structural and biochemical features of
      caspase-activating complexes. By analyzing the structural basis for the assembly
      mechanism of the caspase-activating complex, we hope to provide a comprehensive
      understanding of caspase activation by these important oligomeric complexes.

PMID- 22606011
TI  - Synthesis and antibacterial activities of 1-alkyl-3-methacryloyl (acryloyl) of
      benzimidazolone (thione) derivatives.
AB  - A series of (28) 1-alkyl-3-methacryloyl (acryloyl)-benzimidazolone (thione) deriv
      atives were synthesized. The structures of the new derivatives were confirmed by
      (1)H-NMR, (13)C-NMR and ESI-MS spectral analysis. The antibacterial activities of
      these compounds against several strains of bacteria, such as Bacillus cereus,
      Bacillus subtilis, Escherichia coli, Staphylococcus aureus and Pseudomonas
      aeruginosa, were evaluated by methods of paper disc-diffusion and broth mciro
      dilution. Methacryloyl derivatives displayed higher antibacterial activities
      against tested bacterial strains than those of acryloyl derivatives in in vitro
      tests. A structure-activity relationship (SAR) study revealed that the presences
      of the methacryloyl moieties is essential to the antibacterial activities of the
      compounds.

PMID- 22606007
TI  - Phages and HIV-1: from display to interplay.
AB  - The complex hide-and-seek game between HIV-1 and the host immune system has
      impaired the development of an efficient vaccine. In addition, the high
      variability of the virus impedes the long-term control of viral replication by
      small antiviral drugs. For more than 20 years, phage display technology has been
      intensively used in the field of HIV-1 to explore the epitope landscape
      recognized by monoclonal and polyclonal HIV-1-specific antibodies, thereby
      providing precious data about immunodominant and neutralizing epitopes. In
      parallel, biopanning experiments with various combinatorial or antibody fragment
      libraries were conducted on viral targets as well as host receptors to identify
      HIV-1 inhibitors. Besides these applications, phage display technology has been
      applied to characterize the enzymatic specificity of the HIV-1 protease. Phage
      particles also represent valuable alternative carriers displaying various HIV-1
      antigens to the immune system and eliciting antiviral responses. This review
      presents and summarizes the different studies conducted with regard to the nature
      of phage libraries, target display mode and biopanning procedures.

PMID- 22606012
TI  - Curcumin enhances cytotoxic effects of bortezomib in human multiple myeloma H929
      cells: potential roles of NF-kappaB/JNK.
AB  - Combined curcumin and PS-341 treatment has been reported to enhance cytotoxicity
      and minimize adverse effects through ERK and p38MAPK mechanisms in human multiple
      myeloma cells. However, whether JNK plays similar role in this process remains
      unclear. In the present study, we found combined treatment altered NF-kappaB p65
      expressions and distributions in multiple myeloma H929 cells. Western blot
      analysis showed combined treatment inactivated NF-kappaB while activated JNK
      signaling. Pre-treatment with JNK inhibitor SP600125 could attenuate NF-kappaB
      inactivation and restored H929 cells' survival. These results suggested that
      curcumin might enhance the cytotoxicity of PS-341 by interacting with NF-kappaB,
      at least in part, through JNK mechanism.

PMID- 22606014
TI  - Preparation, characterization and thermal degradation of polyimide (4
      APS/BTDA)/SiO(2) composite films.
AB  - Polyimide/SiO(2) composite films were prepared from tetraethoxysilane (TEOS) and
      poly(amic acid) (PAA) based on aromatic diamine (4-aminophenyl sulfone) (4-APS)
      and aromatic dianhydride (3,3,4,4-benzophenonetetracarboxylic dianhydride) (BTDA)
      via a sol-gel process in N-methyl-2-pyrrolidinone (NMP). The prepared
      polyimide/SiO(2) composite films were characterized using X-ray diffraction
      (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron
      microscope (SEM) and thermogravimetric analysis (TGA). The FTIR results confirmed
      the synthesis of polyimide (4-APS/BTDA) and the formation of SiO(2) particles in
      the polyimide matrix. Meanwhile, the SEM images showed that the SiO(2) particles
      were well dispersed in the polyimide matrix. Thermal stability and kinetic
      parameters of the degradation processes for the prepared polyimide/SiO(2)
      composite films were investigated using TGA in N(2) atmosphere. The activation
      energy of the solid-state process was calculated using Flynn-Wall-Ozawa's method
      without the knowledge of the reaction mechanism. The results indicated that
      thermal stability and the values of the calculated activation energies increased
      with the increase of the TEOS loading and the activation energy also varied with
      the percentage of weight loss for all compositions.

PMID- 22606013
TI  - Quercetin and epigallocatechin gallate induce in vitro a dose-dependent
      stiffening and hyperpolarizing effect on the cell membrane of human mononuclear
      blood cells.
AB  - The bioactivity of polyphenols is closely linked to their ability to interact
      with biological membranes. The study evaluates the in vitro effect of quercetin
      and epigallocatechin on the membrane anisotropy and transmembrane potential of
      peripheral blood mononuclear cells (PBMCs) isolated from 26 type 2 diabetes
      mellitus patients compared to 25 age matched controls. The in vitro assays were
      analyzed in correlation with the biochemical and inflammatory profile of the
      subjects and with insulin resistance parameters (HOMA-IR, plasma resistin) as
      well. For type 2 diabetes patients, the increase of HOMA-IR and resistin
      concentration was associated with a significant decrease of the PBMCs membrane
      anisotropy. The two tested polyphenols induced a dose-dependent hyperpolarizing
      effect and stiffening of the cell membranes for all tested subjects.
      Physiological levels of quercetin and epigallocatechin gallate had the tendency
      to normalize the PBMCs membrane anisotropy of the cells isolated from diabetes
      patients, bringing it to the level of cells isolated from normoglycemic ones.
      Epigallocatechin gallate induced higher effects compared to quercetin on the
      membranes isolated from subjects with higher cardiovascular risk. The decrease of
      membrane fluidity and the hyperpolarizing effect could explain the cardiovascular
      protective action of the tested compounds.

PMID- 22606015
TI  - Study of drug metabolism by xanthine oxidase.
AB  - In this work, we report the studies of drug metabolism by xanthine oxidase (XOD)
      with electrochemical techniques. Firstly, a pair of stable, well-defined and
      quasi-reversible oxidation/reduction peaks is obtained with the formal potential
      at -413.1 mV (vs. SCE) after embedding XOD in salmon sperm DNA membrane on the
      surface of pyrolytic graphite electrode. Then, a new steady peak can be observed
      at -730 mV (vs. SCE) upon the addition of 6-mercaptopurine (6-MP) to the
      electrochemical system, indicating the metabolism of 6-MP by XOD. Furthermore,
      the chronoamperometric response shows that the current of the catalytic peak
      located at -730 mV increases with addition of 6-MP in a concentration-dependent
      manner, and the increase of the chronoamperometric current can be inhibited by an
      XOD inhibitor, quercetin. Therefore, our results prove that XOD/DNA modified
      electrode can be efficiently used to study the metabolism of 6-MP, which may
      provide a convenient approach for in vitro studies on enzyme-catalyzed drug
      metabolism.

PMID- 22606016
TI  - Study on the immunomodulation effect of Isodon japonicus extract via splenocyte
      function and NK anti-tumor activity.
AB  - Here we investigated the potential immune-enhancing activity of Isodon japonicus
      on murine splenocyte and natural-killer (NK) cells in vitro. The ethanol extract
      of I. japonicus significantly enhanced the proliferation of splenocyte and
      induced the significant enhancement of NK cells' activity against tumor cells
      (YAC-1). In addition, I. japonicus increased the production of interferon (IFN)
      gamma and tumor necrosis factor (TNF)-alpha, suggesting that the increase in NK
      cell cytotoxicity could be due to the enhancement of the NK cell production of
      both cytokines. Taken together, I. japonicus extract inhibited the growth of
      human leukemia cells (K562) by 74%. Our observation indicated that the anti-tumor
      effects of I. japonicus may be attributed to its ability to serve as a stimulant
      of NK anti-tumor activity. In addition, our results support the development of
      functional food studies on I. japonicus.

PMID- 22606017
TI  - Development of eighteen microsatellite markers in Anemone amurensis
      (Ranunculaceae) and cross-amplification in congeneric species.
AB  - Polyploidy plays an important role in the evolution of plant genomes. To enable
      the investigation of the polyploidy events within the genus Anemone, we developed
      eighteen microsatellite markers from the hexaploid species A. amurensis
      (Ranunculaceae), and tested their transferability in five closely related
      species. The number of total alleles (N(A)) for each resulting locus varied from
      one to eight. The polymorphism information content (PIC) and Nei's genetic
      diversity (N(GD)) for these microsatellites ranged from 0.00 to 0.71 and 0.00 to
      0.91, respectively. For each population, the N(A) was one to seven, and the
      values of PIC and N(GD) varied from 0.00 to 0.84 and 0.00 to 0.95, respectively.
      In addition, most of these microsatellites can be amplified successfully in the
      congeneric species. These microsatellite primers provide us an opportunity to
      study the polyploid evolution in the genus Anemone.

PMID- 22606018
TI  - Risk-association of CYP11A1 polymorphisms and breast cancer among Han Chinese
      women in Southern China.
AB  - Exposure to endogenous sex hormones has been reported as a risk factor for breast
      cancer. The CYP11A1 gene encodes the key enzyme that catalyzes the initial and
      rate-limiting step in steroid hormone synthesis. In this study, the associations
      between single nucleotide polymorphisms (SNPs) in CYP11A1 and breast cancer
      susceptibility were examined. Six SNPs in CYP11A1 were genotyped using the
      MassARRAY IPLEX platform in 530 breast cancer patients and 546 healthy controls.
      Association analyses based on a chi(2) test and binary logistic regression were
      performed to determine the odds ratio (OR) and 95% confidence interval (95% CI)
      for each SNP. Two loci (rs2959008 and rs2279357) showed evidence of associations
      with breast cancer risk. The variant genotype C/T-C/C of rs2959008 was
      significantly associated with a decreased risk (age-adjusted OR, 0.75; 95% CI,
      0.58-0.96; P = 0.023) compared with the wild-type TT. However, the homozygous TT
      variant of rs2279357 exhibited increased susceptibility to breast cancer (age
      adjusted OR, 1.44; 95% CI, 1.05-1.98; P = 0.022). The locus rs2959003 also showed
      an appreciable effect, but no associations were observed for three other SNPs.
      Our results suggest that polymorphisms of CYP11A1 are related to breast cancer
      susceptibility in Han Chinese women of South China.

PMID- 22606019
TI  - Novel drug delivery system based on docetaxel-loaded nanocapsules as a
      therapeutic strategy against breast cancer cells.
AB  - In the field of cancer therapy, lipid nanocapsules based on a core-shell
      structure are promising vehicles for the delivery of hydrophobic drugs such as
      docetaxel. The main aim of this work was to evaluate whether docetaxel-loaded
      lipid nanocapsules improved the anti-tumor effect of free docetaxel in breast
      cancer cells. Three docetaxel-loaded lipid nanocapsules were synthesized by
      solvent displacement method. Cytotoxic assays were evaluated in breast carcinoma
      (MCF-7) cells treated by the sulforhodamine B colorimetric method. Cell cycle was
      studied by flow cytometry and Annexin V-FITC, and apoptosis was evaluated by
      using propidium iodide assays. The anti-proliferative effect of docetaxel
      appeared much earlier when the drug was encapsulated in lipid nanoparticles than
      when it was free. Docetaxel-loaded lipid nanocapsules significantly enhanced the
      decrease in IC(50) rate, and the treated cells evidenced apoptosis and a
      premature progression of the cell cycle from G(1) to G(2)-M phase. The
      chemotherapeutic effect of free docetaxel on breast cancer cells is improved by
      its encapsulation in lipid nanocapsules. This approach has the potential to
      overcome some major limitations of conventional chemotherapy and may be a
      promising strategy for future applications in breast cancer therapy.

PMID- 22606020
TI  - Structural and functional characterization of two alternative splicing variants
      of mouse Endothelial Cell-Specific Chemotaxis Regulator (ECSCR).
AB  - Endothelial cells (ECs) that line the lumen of blood vessels are important
      players in blood vessel formation, and EC migration is a key component of the
      angiogenic process. Thus, identification of genes that are specifically or
      preferentially expressed in vascular ECs and in-depth understanding of their
      biological functions may lead to discovery of new therapeutic targets. We have
      previously reported molecular characterization of human endothelial cell-specific
      molecule 2 (ECSM2)/endothelial cell-specific chemotaxis regulator (ECSCR). In the
      present study, we cloned two mouse full-length cDNAs by RT-PCR, which encode two
      putative ECSCR isoform precursors with considerable homology to the human ECSCR.
      Nucleotide sequence and exon-intron junction analyses suggested that they are
      alternative splicing variants (ECSCR isoform-1 and -2), differing from each other
      in the first and second exons. Quantitative RT-PCR results revealed that isoform
      2 is the predominant form, which was most abundant in heart, lung, and muscles,
      and moderately abundant in uterus and testis. In contrast, the expression of
      isoform-1 seemed to be more enriched in testis. To further explore their
      potential cellular functions, we expressed GFP- and FLAG-tagged ECSCR isoforms,
      respectively, in an ECSCR deficient cell line (HEK293). Interestingly, the actual
      sizes of either ECSCR-GFP or -FLAG fusion proteins detected by immunoblotting are
      much larger than their predicted sizes, suggesting that both isoforms are
      glycoproteins. Fluorescence microscopy revealed that both ECSCR isoforms are
      localized at the cell surface, which is consistent with the structural
      prediction. Finally, we performed cell migration assays using mouse endothelial
      MS1 cells overexpressing GFP alone, isoform-1-GFP, and isoform-2-GFP,
      respectively. Our results showed that both isoforms significantly inhibited
      vascular epidermal growth factor (VEGF)-induced cell migration. Taken together,
      we have provided several lines of experimental evidence that two mouse ECSCR
      splicing variants/isoform precursors exist. They are differentially expressed in
      a variety of tissue types and likely involved in modulation of vascular EC
      migration. We have also defined the gene structure of mouse ECSCR using
      bioinformatics tools, which provides new information towards a better
      understanding of alternative splicing of ECSCR.

PMID- 22606021
TI  - Generation and characterization of a novel recombinant antibody against 15
      ketocholestane isolated by phage-display.
AB  - The employment of monoclonal antibodies (Mabs) to identify disease-associated
      biomarkers in clinical samples represents the underlying principle for many
      diagnostic tests. To date, these have been principally developed for protein
      targets with few reported applications for lipids due to their hydrophobicity and
      poor immunogenicity. Oxysterols represent a family of lipids implicated in
      diverse human diseases where Mab-based detection assays could have a profound
      effect on their utility as clinical biomarkers. These are usually identified in
      patients' samples by mass- spectrometry based approaches. Here, we describe an
      antibody phage-library based screening methodology for generating a recombinant
      monoclonal antibody (RAb) targeting the oxysterol-15-ketocholestane (15-KA), a
      lipid implicated in multiple sclerosis and Autoimmune Encephalomyelitis (EAE).
      The antibody is highly specific for 15-KA and shows little or no binding activity
      for other closely related oxysterols. We employ RAb2E9 to address the controversy
      over whether 15-KA is a true biomarker for MS/EAE and show that 15-KA is
      undetectable in serum taken from mice with EAE using antibody based detection
      methodologies; a finding confirmed by mass-spectrometry analysis. This study
      demonstrates the technical feasibility of using phage display to isolate highly
      specific antibodies against poorly immunogenic, small molecule lipids.

PMID- 22606022
TI  - Mycoflora and ochratoxin a control in wheat grain using natural extracts obtained
      from wine industry by-products.
AB  - The aim of this study was to evaluate the effect of some natural extracts
      obtained from grape pomace (GPE) and grape seeds (GSE) as compared to a synthetic
      food, antioxidant-butylated hydroxytoluene (BHT), in order to control fungal
      population and ochratoxin A (OTA) production in naturally contaminated wheat. The
      results showed that the addition of these extracts was efficient with OTA content
      decreasing. On treatment with these extracts the loss of OTA content after 14
      days was in the range 7.8-28.3% relative to the control sample, but increased up
      to 26.48-37% after 28 days. The highest loss in OTA content was recorded for
      treatment with GPE at the 500 ppm level. Regarding the fungal development, the
      obtained results show that the total fungal populations were significantly
      reduced by using natural extracts. The most efficient extract was GPE. Both BHT
      and GPE inhibit the growth of Penicillium verrrucosum, for all doses, but less
      with Aspergillus genera. GPE affects the growth of other types of moulds such as
      Rhizopus microsporus, Fusarium graminearum, Alternaria infectoria and
      Cladosporium herbarum. Our data suggested that GPE and GSE are able to provide
      fungicidal and fungistatic protection and to control the OTA accumulation in
      wheat, at least in a similar manner to BHT.

PMID- 22606023
TI  - 2-decenoic acid ethyl ester, a compound that elicits neurotrophin-like
      intracellular signals, facilitating functional recovery from cerebral infarction
      in mice.
AB  - In our previous study, we found that trans-2-decenoic acid ethyl ester (DAEE), a
      derivative of a medium-chain fatty acid, elicits neurotrophin-like signals
      including the activation of extracellular signal-regulated kinases 1 and 2
      (ERK1/2) in cultured mouse cortical neurons. Here, we examined the efficacy of
      intraperitoneal administration of DAEE on the treatment of a mouse model of the
      cerebral infarction caused by unilateral permanent middle cerebral artery
      occlusion (PMCAO). DAEE-treatment (100 MUg/kg body weight injected at 0.5, 24,
      48, 72 h after PMCAO) significantly restored the mice from PMCAO-induced
      neurological deficits including motor paralysis when evaluated 48, 72, and 96 h
      after the PMCAO. Furthermore, DAEE facilitated the phosphorylation of ERK1/2 on
      the infarction side of the brain when analyzed by Western immunoblot analysis,
      and it enhanced the number of phosphorylated ERK1/2-positive cells in the border
      areas between the infarction and non-infarction regions of the cerebral cortex,
      as estimated immunohistochemically. As the infarct volume remained unchanged
      after DAEE-treatment, it is more likely that DAEE improved the neurological
      condition through enhanced neuronal functions of the remaining neurons in the
      damaged areas rather than by maintaining neuronal survival. These results suggest
      that DAEE has a neuro-protective effect on cerebral infarction.

PMID- 22606024
TI  - Synthesis, spectral and antibacterial sudies of copper(II) tetraaza macrocyclic
      complexes.
AB  - A novel family of tetraaza macrocyclic Cu(II) complexes [CuLX(2)] (where L = N(4)
      donor macrocyclic ligands) and (X = Cl(-), NO(3) (-)) have been synthesized and
      characterized by elemental analysis, magnetic moments, IR, EPR, mass, electronic
      spectra and thermal studies. The magnetic moments and electronic spectral studies
      suggest square planar geometry for [Cu(DBACDT)]Cl(2) and [Cu(DBACDT)](NO(3))(2)
      complexes and distorted octahedral geometry to the rest of the ten complexes. The
      biological activity of all these complexes against gram-positive and gram
      negative bacteria was compared with the activity of existing commercial
      antibacterial compounds like Linezolid and Cefaclor. Six complexes out of twelve
      were found to be most potent against both gram-positive as well as gram-negative
      bacteria due to the presence of thio group in the coordinated ligands.

PMID- 22606025
TI  - Effects of inflorescence stem structure and cell wall components on the
      mechanical strength of inflorescence stem in herbaceous peony.
AB  - Herbaceous peony (Paeonia lactiflora Pall.) is a traditional famous flower, but
      its poor inflorescence stem quality seriously constrains the development of the
      cut flower. Mechanical strength is an important characteristic of stems, which
      not only affects plant lodging, but also plays an important role in stem bend or
      break. In this paper, the mechanical strength, morphological indices and
      microstructure of P. lactiflora development inflorescence stems were measured and
      observed. The results showed that the mechanical strength of inflorescence stems
      gradually increased, and that the diameter of inflorescence stem was a direct
      indicator in estimating mechanical strength. Simultaneously, with the development
      of inflorescence stem, the number of vascular bundles increased, the vascular
      bundle was arranged more densely, the sclerenchyma cell wall thickened, and the
      proportion of vascular bundle and pith also increased. On this basis, cellulose
      and lignin contents were determined, PlCesA3, PlCesA6 and PlCCoAOMT were isolated
      and their expression patterns were examined including PlPAL. The results showed
      that cellulose was not strictly correlated with the mechanical strength of
      inflorescence stem, and lignin had a significant impact on it. In addition,
      PlCesA3 and PlCesA6 were not key members in cellulose synthesis of P. lactiflora
      and their functions were also different, but PlPAL and PlCCoAOMT regulated the
      lignin synthesis of P. lactiflora. These data indicated that PlPAL and PlCCoAOMT
      could be applied to improve the mechanical strength of P. lactiflora
      inflorescence stem in genetic engineering.

PMID- 22606026
TI  - Aristolactam-type alkaloids from Orophea enterocarpa and their cytotoxicities.
AB  - A new aristolactam, named enterocarpam-III (10-amino-2,3,4,6-tetramethoxy
      phenanthrene-1-carboxylic acid lactam, 1) together with the known alkaloid
      stigmalactam (2), were isolated from Orophea enterocarpa. Their structures were
      elucidated on the basis of interpretation of their spectroscopic data. Compounds
      1 and 2 exhibited significant cytotoxicities against human colon adenocarcinoma
      (HCT15) cell line with IC(50) values of 1.68 and 1.32 MUM, respectively.

PMID- 22606027
TI  - Na(+), K(+)-ATPase subunit composition in a human chondrocyte cell line; evidence
      for the presence of alpha1, alpha3, beta1, beta2 and beta3 isoforms.
AB  - Membrane transport systems participate in fundamental activities such as cell
      cycle control, proliferation, survival, volume regulation, pH maintenance and
      regulation of extracellular matrix synthesis. Multiple isoforms of Na(+), K(+)
      ATPase are expressed in primary chondrocytes. Some of these isoforms have
      previously been reported to be expressed exclusively in electrically excitable
      cells (i.e., cardiomyocytes and neurons). Studying the distribution of Na(+),
      K(+)-ATPase isoforms in chondrocytes makes it possible to document the diversity
      of isozyme pairing and to clarify issues concerning Na(+), K(+)-ATPase isoform
      abundance and the physiological relevance of their expression. In this study, we
      investigated the expression of Na(+), K(+)-ATPase in a human chondrocyte cell
      line (C-20/A4) using a combination of immunological and biochemical techniques. A
      panel of well-characterized antibodies revealed abundant expression of the
      alpha1, beta1 and beta2 isoforms. Western blot analysis of plasma membranes
      confirmed the above findings. Na(+), K(+)-ATPase consists of multiple isozyme
      variants that endow chondrocytes with additional homeostatic control
      capabilities. In terms of Na(+), K(+)-ATPase expression, the C-20/A4 cell line is
      phenotypically similar to primary and in situ chondrocytes. However, unlike
      freshly isolated chondrocytes, C-20/A4 cells are an easily accessible and
      convenient in vitro model for the study of Na(+), K(+)-ATPase expression and
      regulation in chondrocytes.

PMID- 22606028
TI  - A novel and expedient approach to new thiazoles, thiazolo[3,2-a]pyridines,
      dihydrothiophenes, and hydrazones incorporating thieno[2,3-b]thiophene moiety.
AB  - This paper reports details about the synthesis of a series of novel
      functionalized symmetrical bis-heterocyclic compounds containing a thieno[2,3
      b]thiophene motif. Bis-thiazole derivatives 2, 3a-c and thiazolo[3,2-a]pyridine
      derivatives 4a-c are achieved. The hitherto unknown dihydrothiophene derivatives
      6a-dvia bis-pyridimium salt 5 are obtained. Additionally, the novel
      hydrazonothieno[2,3-b]thiophene derivatives 10a-c are obtained via bis
      tosylacetylthieno[2,3-b]thiophene derivative 9. All compounds are characterized
      by (1)H-, (13)C-NMR, GCMS, IR, and UV-vis spectrometry. These compounds represent
      a new class of sulfur and nitrogen containing heterocycles that should also be of
      interest as new materials.

PMID- 22606029
TI  - Nonselective blocking of the sympathetic nervous system decreases detrusor
      overactivity in spontaneously hypertensive rats.
AB  - The involuntary dual control systems of the autonomic nervous system (ANS) in the
      bladder of awake spontaneously hypertensive rats (SHRs) were investigated through
      simultaneous registrations of intravesical and intraabdominal pressures to
      observe detrusor overactivity (DO) objectively as a core symptom of an overactive
      bladder. SHRs (n = 6) showed the features of overactive bladder syndrome during
      urodynamic study, especially DO during the filling phase. After injection of the
      nonselective sympathetic blocking agent labetalol, DO disappeared in 3 of 6 SHRs
      (50%). DO frequency decreased from 0.98 +/- 0.22 min(-1) to 0.28 +/- 0.19 min(-1)
      (p < 0.01), and DO pressure decreased from 3.82 +/- 0.57 cm H(2)O to 1.90 +/-
      0.86 cm H(2)O (p < 0.05). This suggests that the DO originating from the
      overactive parasympathetic nervous system is attenuated by the nonselective
      blocking of the sympathetic nervous system. The detailed mechanism behind this
      result is still not known, but parasympathetic overactivity seems to require
      overactive sympathetic nervous system activity in a kind of balance between these
      two systems. These findings are consistent with recent clinical findings
      suggesting that patients with idiopathic overactive bladder may have ANS
      dysfunction, particularly a sympathetic dysfunction. The search for newer and
      better drugs than the current anticholinergic drugs as the mainstay for
      overactive bladder will be fueled by our research on these sympathetic
      mechanisms. Further studies of this principle are required.

PMID- 22606030
TI  - Preparation and characterization of micronized artemisinin via a Rapid Expansion
      of Supercritical Solutions (RESS) Method.
AB  - The particle sizes of pharmaceutical substances are important for their
      bioavailability. Bioavailability can be improved by reducing the particle size of
      the drug. In this study, artemisinin was micronized by the rapid expansion of
      supercritical solutions (RESS). The particle size of the unprocessed white needle
      like artemisinin particles was 30 to 1200 MUm. The optimum micronization
      conditions are determined as follows: extraction temperature of 62  degrees C,
      extraction pressure of 25 MPa, precipitation temperature 45  degrees C and nozzle
      diameter of 1000 MUm. Under the optimum conditions, micronized artemisinin with a
      (mean particle size) MPS of 550 nm is obtained. By analysis of variance (ANOVA),
      extraction temperature and pressure have significant effects on the MPS of the
      micronized artemisinin. The particle size of micronized artemisinin decreased
      with increasing extraction temperature and pressure. Moreover, the SEM, LC-MS,
      FTIR, DSC and XRD allowed the comparison between the crystalline initial state
      and the micronization particles obtained after the RESS process. The results
      showed that RESS process has not induced degradation of artemisinin and that
      processed artemisinin particles have lower crystallinity and melting point. The
      bulk density of artemisinin was determined before and after RESS process and the
      obtained results showed that it passes from an initial density of 0.554 to 0.128
      g.cm(-3) after the processing. The decrease in bulk density of the micronized
      powder can increase the liquidity of drug particles when they are applied for
      medicinal preparations. These results suggest micronized powder of artemisinin
      can be of great potential in drug delivery systems.

PMID- 22606031
TI  - Rhinacanthus nasutus extracts prevent glutamate and amyloid-beta neurotoxicity in
      HT-22 mouse hippocampal cells: possible active compounds include lupeol,
      stigmasterol and beta-sitosterol.
AB  - The Herb Rhinacanthus nasutus (L.) Kurz, which is native to Thailand and
      Southeast Asia, has become known for its antioxidant properties. Neuronal loss in
      a number of diseases including Alzheimer's disease is thought to result, in part,
      from oxidative stress. Glutamate causes cell death in the mouse hippocampal cell
      line, HT-22, by unbalancing redox homeostasis, brought about by a reduction in
      glutathione levels, and amyloid-beta has been shown to induce reactive oxygen
      species (ROS) production. Here in, we show that ethanol extracts of R. nasutus
      leaf and root are capable of dose dependently attenuating the neuron cell death
      caused by both glutamate and amyloid-beta treatment. We used free radical
      scavenging assays to measure the extracts antioxidant activities and as well as
      quantifying phenolic, flavonoid and sterol content. Molecules found in R.
      nasutus, lupeol, stigmasterol and beta-sitosterol are protective against
      glutamate toxicity.

PMID- 22606032
TI  - The establishment of a primary culture system of proximal tubule segments using
      specific markers from normal mouse kidneys.
AB  - The proximal tubule contains the highest expression of angiotensinogen mRNA and
      protein within the kidney and plays a vital role in the renal renin-angiotensin
      system. To study the regulation of angiotensinogen expression in the kidney in
      more detail, the proximal tubule needs to be accurately isolated from the rest of
      the nephron and separated into its three segments. The purpose of this study was
      to design a novel protocol using specific markers for the separation of proximal
      tubule cells into the three proximal tubule segments and to determine
      angiotensinogen expression in each segment. Kidneys were removed from C57BL/6J
      mice. The proximal tubules were aspirated from region of a Percoll gradient
      solution of the appropriate density. The proximal tubule was then separated into
      its three segments using segment-specific membrane proteins, after which each
      segment was characterized by a different specific marker (sodium-glucose
      transporter 2 for Segment 1; carbonic anhydrase IV for Segment 2; ecto-adenosine
      triphosphatase for Segment 3). The isolation of proximal tubules into three
      segments was successful, and angiotensinogen mRNA in Segment 2 and 3 and
      angiotensinogen protein in all three segments were confirmed. This protocol will
      be helpful for future studies of the detailed mechanisms of the intrarenal renin
      angiotensin system.

PMID- 22606033
TI  - Genome-wide identification and in silico analysis of poplar peptide deformylases.
AB  - Peptide deformylases (PDF) behave as monomeric metal cation hydrolases for the
      removal of the N-formyl group (Fo). This is an essential step in the N-terminal
      Met excision (NME) that occurs in these proteins from eukaryotic mitochondria or
      chloroplasts. Although PDFs have been identified and their structure and function
      have been characterized in several herbaceous species, it remains as yet
      unexplored in poplar. Here, we report on the first identification of two genes
      (PtrPDF1A and PtrPDF1B) respectively encoding two putative PDF polypeptides in
      Populus trichocarpa by genome-wide investigation. One of them (XP_002300047.1)
      encoded by PtrPDF1B (XM_002300011.1) was truncated, and then revised into a
      complete sequence based on its ESTs support with high confidence. We document
      that the two PDF1s of Populus are evolutionarily divergent, likely as a result of
      independent duplicated events. Furthermore, in silico simulations demonstrated
      that PtrPDF1A and PtrPDF1B should act as similar PDF catalytic activities to
      their corresponding PDF orthologs in Arabidopsis. This result would be value of
      for further assessment of their biological activities in poplar, and further
      experiments are now required to confirm them.

PMID- 22606034
TI  - A DNA network as an information processing system.
AB  - Biomolecular systems that can process information are sought for computational
      applications, because of their potential for parallelism and miniaturization and
      because their biocompatibility also makes them suitable for future biomedical
      applications. DNA has been used to design machines, motors, finite automata,
      logic gates, reaction networks and logic programs, amongst many other structures
      and dynamic behaviours. Here we design and program a synthetic DNA network to
      implement computational paradigms abstracted from cellular regulatory networks.
      These show information processing properties that are desirable in artificial,
      engineered molecular systems, including robustness of the output in relation to
      different sources of variation. We show the results of numerical simulations of
      the dynamic behaviour of the network and preliminary experimental analysis of its
      main components.

PMID- 22606036
TI  - Application of ionic liquids in the microwave-assisted extraction of
      proanthocyanidins from Larix gmelini bark.
AB  - Ionic liquid based, microwave-assisted extraction (ILMAE) was successfully
      applied to the extraction of proanthocyanidins from Larix gmelini bark. In this
      work, in order to evaluate the performance of ionic liquids in the microwave
      assisted extraction process, a series of 1-alkyl-3-methylimidazolium ionic
      liquids with different cations and anions were evaluated for extraction yield,
      and 1-butyl-3-methylimidazolium bromide was selected as the optimal solvent. In
      addition, the ILMAE procedure for the proanthocyanidins was optimized and
      compared with other conventional extraction techniques. Under the optimized
      conditions, satisfactory extraction yield of the proanthocyanidins was obtained.
      Relative to other methods, the proposed approach provided higher extraction yield
      and lower energy consumption. The Larix gmelini bark samples before and after
      extraction were analyzed by Thermal gravimetric analysis, Fourier-transform
      infrared spectroscopy and characterized by scanning electron microscopy. The
      results showed that the ILMAE method is a simple and efficient technique for
      sample preparation.

PMID- 22606035
TI  - Identification of important chemical features of 11beta-hydroxysteroid
      dehydrogenase type1 inhibitors: application of ligand based virtual screening and
      density functional theory.
AB  - 11beta-Hydroxysteroid dehydrogenase type1 (11betaHSD1) regulates the conversion
      from inactive cortisone to active cortisol. Increased cortisol results in
      diabetes, hence quelling the activity of 11betaHSD1 has been thought of as an
      effective approach for the treatment of diabetes. Quantitative hypotheses were
      developed and validated to identify the critical chemical features with reliable
      geometric constraints that contribute to the inhibition of 11betaHSD1 function.
      The best hypothesis, Hypo1, which contains one-HBA; one-Hy-Ali, and two-RA
      features, was validated using Fischer's randomization method, a test and a decoy
      set. The well validated, Hypo1, was used as 3D query to perform a virtual
      screening of three different chemical databases. Compounds selected by Hypo1 in
      the virtual screening were filtered by applying Lipinski's rule of five, ADMET,
      and molecular docking. Finally, five hit compounds were selected as virtual novel
      hit molecules for 11betaHSD1 based on their electronic properties calculated by
      Density functional theory.

PMID- 22606037
TI  - Filamentous bacteriophage fd as an antigen delivery system in vaccination.
AB  - Peptides displayed on the surface of filamentous bacteriophage fd are able to
      induce humoral as well as cell-mediated immune responses, which makes phage
      particles an attractive antigen delivery system to design new vaccines. The
      immune response induced by phage-displayed peptides can be enhanced by targeting
      phage particles to the professional antigen presenting cells, utilizing a single
      chain antibody fragment that binds dendritic cell receptor DEC-205. Here, we
      review recent advances in the use of filamentous phage fd as a platform for
      peptide vaccines, with a special focus on the use of phage fd as an antigen
      delivery platform for peptide vaccines in Alzheimer's Disease and cancer.

PMID- 22606038
TI  - Localization of axonal motor molecules machinery in neurodegenerative disorders.
AB  - Axonal transport and neuronal survival depend critically on active transport and
      axon integrity both for supplying materials and communication to different
      domains of the cell body. All these actions are executed through cytoskeleton,
      transport and regulatory elements that appear to be disrupted in
      neurodegenerative diseases. Motor-driven transport both supplies and clears
      distal cellular portions with proteins and organelles. This transport is
      especially relevant in projection and motor neurons, which have long axons to
      reach the farthest nerve endings. Thus, any disturbance of axonal transport may
      have severe consequences for neuronal function and survival. A growing body of
      literature indicates the presence of alterations to the motor molecules
      machinery, not only in expression levels and phosphorylation, but also in their
      subcellular distribution within populations of neurons, which are selectively
      affected in the course of neurodegenerative diseases. The implications of this
      altered subcellular localization and how this affects axon survival and neuronal
      death still remain poorly understood, although several hypotheses have been
      suggested. Furthermore, cytoskeleton and transport element localization can be
      selectively disrupted in some disorders suggesting that specific loss of the
      axonal functionality could be a primary hallmark of the disorder. This can lead
      to axon degeneration and neuronal death either directly, through the functional
      absence of essential axonal proteins, or indirectly, through failures in
      communication among different cellular domains. This review compares the
      localization of cytoskeleton and transport elements in some neurodegenerative
      disorders to ask what aspects may be essential for axon survival and neuronal
      death.

PMID- 22606039
TI  - Poisson parameters of antimicrobial activity: a quantitative structure-activity
      approach.
AB  - A contingency of observed antimicrobial activities measured for several compounds
      vs. a series of bacteria was analyzed. A factor analysis revealed the existence
      of a certain probability distribution function of the antimicrobial activity. A
      quantitative structure-activity relationship analysis for the overall
      antimicrobial ability was conducted using the population statistics associated
      with identified probability distribution function. The antimicrobial activity
      proved to follow the Poisson distribution if just one factor varies (such as
      chemical compound or bacteria). The Poisson parameter estimating antimicrobial
      effect, giving both mean and variance of the antimicrobial activity, was used to
      develop structure-activity models describing the effect of compounds on bacteria
      and fungi species. Two approaches were employed to obtain the models, and for
      every approach, a model was selected, further investigated and found to be
      statistically significant. The best predictive model for antimicrobial effect on
      bacteria and fungi species was identified using graphical representation of
      observed vs. calculated values as well as several predictive power parameters.

PMID- 22606040
TI  - Enhanced production of a novel cyclic hexapeptide antibiotic (NW-G01) by
      Streptomyces alboflavus 313 using response surface methodology.
AB  - NW-G01, produced by Streptomyces alboflavus 313, is a novel cyclic hexapeptide
      antibiotic with many potential applications, including antimicrobial activity and
      antitumor agents. This study developed a system for optimizing medium components
      in order to enhance NW-G01 production. In this study, Plackett-Burman design
      (PBD) was used to find the key ingredients of medium components, and then
      response surface methodology (RSM) was implemented to determine their optimal
      concentrations. The results of PBD revealed that the crucial ingredients related
      to the production of NW-G01 were (NH(4))(2)SO(4), peptone and CaCO(3). A
      prediction model has been built in the experiments of central composite design
      and response surface methodology, and its validation has been further verified.
      The optimal medium composition was determined (g/L): corn starch 15, glucose 15,
      peptone 3.80, (NH(4))(2)SO(4) 0.06, NaCl 1.5, CaCO(3) 1.30, MgSO(4).7H(2)O 0.015,
      K(2)HPO(4).3H(2)O 0.015, MnCl(2).4H(2)O 0.015, FeSO(4).7H(2)O 0.015, and
      ZnSO(4).7H(2)O 0.015. Compared with NW-G01 production (5.707 mg/L) in non
      optimized fermentation medium, the production of NW-G01 (15.564 mg/L) in
      optimized fermentation medium had a 2.73-fold increase.

PMID- 22606041
TI  - Sol-gel-derived hydroxyapatite-carbon nanotube/titania coatings on titanium
      substrates.
AB  - In this paper, hydroxyapatite-carbon nanotube/titania (HA-CNT/TiO(2)) double
      layer coatings were successfully developed on titanium (Ti) substrates intended
      for biomedical applications. A TiO(2) coating was firstly developed by
      anodization to improve bonding between HA and Ti, and then the layer of HA and
      CNTs was coated on the surface by the sol-gel process to improve the
      biocompatibility and mechanical properties of Ti. The surfaces of double layer
      coatings were uniform and crack-free with a thickness of about 7 MUm. The bonding
      strength of the HA-CNT/TiO(2) coating was higher than that of the pure HA and HA
      CNT coatings. Additionally, in vitro cell experiments showed that CNTs promoted
      the adhesion of preosteoblasts on the HA-CNT/TiO(2) double layer coatings. These
      unique surfaces combined with the osteoconductive properties of HA exhibited the
      excellent mechanical properties of CNTs. Therefore, the developed HA-CNT/TiO(2)
      coatings on Ti substrates might be a promising material for bone replacement.

PMID- 22606043
TI  - Synthesis mechanism of low-voltage praseodymium oxide doped zinc oxide varistor
      ceramics prepared through modified citrate gel coating.
AB  - High demands on low-voltage electronics have increased the need for zinc oxide
      (ZnO) varistors with fast response, highly non-linear current-voltage
      characteristics and energy absorption capabilities at low breakdown voltage.
      However, trade-off between breakdown voltage and grain size poses a critical
      bottle-neck in the production of low-voltage varistors. The present study
      highlights the synthesis mechanism for obtaining praseodymium oxide (Pr(6)O(11))
      based ZnO varistor ceramics having breakdown voltages of 2.8 to 13.3 V/mm through
      employment of direct modified citrate gel coating technique. Precursor powder and
      its ceramics were examined by means of TG/DTG, FTIR, XRD and FESEM analyses. The
      electrical properties as a function of Pr(6)O(11) addition were analyzed on the
      basis of I-V characteristic measurement. The breakdown voltage could be adjusted
      from 0.01 to 0.06 V per grain boundary by controlling the amount of Pr(6)O(11)
      from 0.2 to 0.8 mol%, without alteration of the grain size. The non-linearity
      coefficient, alpha, varied from 3.0 to 3.5 and the barrier height ranged from
      0.56 to 0.64 eV. Breakdown voltage and alpha lowering with increasing Pr(6)O(11)
      content were associated to reduction in the barrier height caused by variation in
      O vacancies at grain boundary.

PMID- 22606044
TI  - Donepezil combined with natural hirudin improves the clinical symptoms of
      patients with mild-to-moderate Alzheimer's disease: a 20-week open-label pilot
      study.
AB  - AIM: To evaluate the efficacy and safety of donepezil plus natural hirudin in
      patients with mild-to-moderate Alzheimer's Disease. METHODS: In the 20-week,
      randomized, open-label and controlled study, 84 patients received either
      donepezil (5 mg/day for the first 4 weeks and 10 mg/day thereafter) or donepezil
      plus natural hirudin (3 g/day) treatment. Efficacy was reflected by the change of
      the total scores of Alzheimer's Disease Assessment Scale cognitive subscale (ADAS
      Cog), Activities of Daily Life (ADL) and Neuropsychiatric Inventory (NPI).
      RESULTS: The patients with the donepezil plus natural hirudin treatment showed
      more significant improvement in the daily activities and the decline of the
      cognition than those with donepezil treatment. Significant difference was present
      in the groups since the 8th week. No group difference was found in the NPI
      change. However, within the hirudin treatment group, more powerful efficacy
      including NPI assessment was found in the patients with vascular risk factors
      (VRF) as comparing to with those without VRF. The combination of donepezil and
      natural hirudin was well tolerated. The dropout rate was greater in the donepezil
      and natural hirudin (50%) treatment group than in the donepezil (39%) treatment
      group. Similar result was found in the incidence of adverse events (23.8% vs
      19.0%), but there was no statistical difference between the two groups. Adverse
      events were the most common reason for the dropout. Although hemorrhage and
      hypersensitiveness were more common in donepezil plus Maixuekang treatment (11.9%
      and 7.1%) group than in donepezil treatment (2.4% and 2.4%) group, no significant
      difference was present between the two groups. Economic problem was another
      important reason for the patients' withdrawal. CONCLUSIONS: Compared with the
      donepezil treatment in the patients with mild-to-moderate AD, our results suggest
      that donepezil combined with natural hirudin may improve the treatment effects in
      the ADL, BPSD and cognition of the patients. Furthermore, this joint treatment is
      safe.

PMID- 22606042
TI  - Phage displayed peptides/antibodies recognizing growth factors and their tyrosine
      kinase receptors as tools for anti-cancer therapeutics.
AB  - The basic idea of displaying peptides on a phage, introduced by George P. Smith
      in 1985, was greatly developed and improved by McCafferty and colleagues at the
      MRC Laboratory of Molecular Biology and, later, by Barbas and colleagues at the
      Scripps Research Institute. Their approach was dedicated to building a system for
      the production of antibodies, similar to a naive B cell repertoire, in order to
      by-pass the standard hybridoma technology that requires animal immunization. Both
      groups merged the phage display technology with an antibody library to obtain a
      huge number of phage variants, each of them carrying a specific antibody ready to
      bind its target molecule, allowing, later on, rare phage (one in a million) to be
      isolated by affinity chromatography. Here, we will briefly review the basis of
      the technology and the therapeutic application of phage-derived bioactive
      molecules when addressed against key players in tumor development and
      progression: growth factors and their tyrosine kinase receptors.

PMID- 22606045
TI  - Relationship between oral anaerobic bacteria and otitis media with effusion.
AB  - OBJECTIVE: In this study hypothesing the translocation of oral bacteria from
      oropharynx into the middle ear cavity may be involved in the pathogenesis of
      otitis media with effusion (OME), we aimed to investigate the presence and
      similarity of Fusobacterium nucleatum and Treponema denticola in saliva,
      nasopharyngeal secretion and the middle ear effusion samples from the children
      with OME. METHODS: Totally 20 children with OME undergoing myringotomy and
      ventilation tube placement were attended. Stimulated saliva samples were
      collected after otorhinolaryngological and oral examinations were done. The
      middle ear effusion and nasopharyngeal secretions were collected during the
      operations. The presence of F. nucleatum and T. denticola were detected using
      16SrRNA-based PCR. The clonal similarities of the bacteria were detected in the
      samples which the same bacteria had been detected in each samples of the same
      child. After DNA sequencing, clonal similarity was determined by 16SrRNA gene
      clone library analysis. The sequences from each clone were compared with similar
      sequences of reference organisms by FASTA search. RESULTS: T. denticola was
      detected only in four (20%) saliva and in one (5%) nasopharyngeal sample. F.
      nucleatum was detected in 11 (55%) saliva, eight (40%) nasopharyngeal and six
      (30%) middle ear effusion samples. Sequences from F.nucleatum clones derived from
      three different anatomic sites within patients were similar in 33% of OME
      patients, indicating their genetic relatedness. CONCLUSIONS: Bacteria involved in
      this process most likely originate from the oropharynx since they show a close
      genetic relatedness with their oropharyngeal counterparts.

PMID- 22606046
TI  - Selection of peptide inhibitor to matrix metalloproteinase-2 using phage display
      and its effects on pancreatic cancer cell lines PANC-1 and CFPAC-1.
AB  - Despite tremendous advances in cancer treatment and survival rates, pancreatic
      cancer remains one of the most deadly afflictions and the fourth leading cause of
      cancer deaths in the world. Matrix Metalloproteinases (MMPs) are thought to be
      involved in cancer progression. Matrix metalloproteinase (MMP)-2 is known to play
      a pivotal role in tumor invasion, metastasis and angiogenesis, and validated to
      be the anticancer target. Inhibition of MMP-2 activity is able to reduce the
      cancer cell invasion and suppress tumor growth in vivo. Two novel peptides,
      M204C4 and M205C4, which could specially inhibit MMP-2 activity, were identified
      by a phage display library screening. We showed that M204C4 and M205C4 inhibited
      the activity of MMP-2 in a dose dependent manner in vitro. Two peptides reduced
      MMP-2 mediated invasion of the pancreatic cancer cell lines PANC-1 and CFPAC-1,
      but not affected the expression and release of MMP-2. Furthermore, these two
      peptides could suppress tumor growth in vivo. Our results indicated that two
      peptides selected by phase display technology may be used as anticancer drugs in
      the future.

PMID- 22606047
TI  - Fibroblast growth factor-23 helps explain the biphasic cardiovascular effects of
      vitamin D in chronic kidney disease.
AB  - Hypovitaminosis D is highly prevalent in chronic kidney disease (CKD). Recently,
      vitamin D has sparked widespread interest because of its potential favorable
      benefits on cardiovascular disease (CVD). Evidence from clinical studies and
      animal models supports the existence of biphasic cardiovascular effects of
      vitamin D, in which lower doses suppress CVD and higher doses stimulate CVD.
      However, the mechanism for the different effects remains unclear. Fibroblast
      growth factor-23 (FGF-23) is a recently identified member of the FGF family, and
      thought to be actively involved in renal phosphate and vitamin D homeostasis.
      More specifically, Vitamin D stimulates FGF-23 secretion and is inhibited by
      increased FGF-23. Given this background, we hypothesize that FGF-23 may provide a
      unique tool to explain the biphasic cardiovascular effects of vitamin D in CKD.
      The data presented in this review support the hypothesis that FGF-23 may be
      linked with the high cardiovascular risk in CKD through accelerating the onset of
      vascular calcification, secondary hyperparathyroidism, left ventricular
      hypertrophy and endothelial dysfunction. Therefore, modulation of FGF-23 may
      become a potential therapeutic target to lowing cardiovascular risk in CKD.
      Several clinical interventions, including decreased phosphate intake, phosphate
      binders, cinacalcet plus concurrent low-dose vitamin D, C-terminal tail of FGF-23
      and renal transplantation, have been employed to manipulate FGF-23.

PMID- 22606050
TI  - Regional prevalence of short stature in Saudi school-age children and
      adolescents.
AB  - OBJECTIVE: To assess the magnitude of regional difference in prevalence of short
      stature in Saudi children and adolescents. SUBJECTS AND METHODS: A representative
      sample from three different regions of the Kingdom of Saudi Arabia (KSA) (North,
      Southwest, and Center) was used to calculate the prevalence of short stature
      (standard deviation score less than -2) in children 5 to 17 years of age.
      RESULTS: There were 9018 children and adolescents from 5 to 17 years of age
      (3366, 2825, and 2827 in the Northern, Southwestern and Central regions, resp.)
      and 51% were boys. In both school-age children and adolescents, there was a
      significantly higher prevalence of short stature in the Southwestern than in the
      Northern or the Central region (P < 0.0001). CONCLUSION: The finding of
      significant regional variation between regions helps in planning priorities for
      research and preventive measures.

PMID- 22606051
TI  - Vascular function and handgrip strength in rheumatoid arthritis patients.
AB  - OBJECTIVE: To examine the relationship of handgrip strength with forearm blood
      flow (BF) and vascular resistance (VR) in rheumatoid arthritis (RA) patients.
      METHODS: Forearm BF at rest (RBF) and after upper arm occlusion (RHBF), and
      handgrip strength were examined in 78 individuals (RA = 42 and controls (CT) =
      36). Subsequently, VR at rest (RVR) and after occlusion (RHVR) were calculated.
      RESULTS: The patients' RBF (P = 0.02) and RHBF (P = 0.0001) were less, whereas
      RVR (P = 0.002) and RHVR (P = 0.0001) were greater as compared to the CTs.
      Similarly, handgrip strength was lower in the RAs (P = 0.0001). Finally, handgrip
      strength was directly associated with RBF (r = 0.43; P = 0.0001), and RHBF (r =
      0.5; P = 0.0001), and inversely related to RVR (r = -0.3; P = 0.009) and RHVR (r
      = -0.3; P = 0.007). CONCLUSION: The present study uniquely identifies an
      association between regional measures of forearm blood flow and handgrip strength
      in patients and healthy control. In addition, this study confirms the presence of
      vascular and muscle dysfunction in patients with rheumatoid arthritis, as
      evidenced by lower forearm blood flow indices, at rest and following occlusion,
      and lower handgrip strength as compared to healthy individuals.

PMID- 22606049
TI  - Interactions of several lipid-related gene polymorphisms and cigarette smoking on
      blood pressure levels.
AB  - The interactions of single nucleotide polymorphisms (SNPs) and cigarette smoking
      on blood pressure levels are limited. The present study was undertaken to detect
      nine lipid-related SNPs and their interactions with cigarette smoking on blood
      pressure levels. Genotyping of ATP-binding cassette transporter A1 (ABCA-1)
      V825I, acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) rs1044925, low density
      lipoprotein receptor (LDL-R) AvaII, hepatic lipase gene (LIPC) -250G>A,
      endothelial lipase gene (LIPG) 584C>T, methylenetetrahydrofolate reductase
      (MTHFR) 677C>T, proprotein convertase subtilisin-like kexin type 9 (PCSK9) E670G,
      peroxisome proliferator-activated receptor delta (PPARD) +294T>C, and Scavenger
      receptor class B type 1 (SCARB1) rs5888 was performed in 935 nonsmokers and 845
      smokers. The interactions were detected by factorial regression analysis. The
      frequencies of genotypes (ACAT-1 and LIPG), alleles (ABCA-1), and both genotypes
      and alleles (LDL-R, LIPC, PPARD and SCARB1) were different between nonsmokers and
      smokers (P < 0.05-0.001). The levels of pulse pressure (PP, ABCA-1), and
      systolic, diastolic blood pressure (SBP, DBP) and PP (LIPC) in nonsmokers were
      different among the genotypes (P < 0.01-0.001). The levels of SBP (ABCA-1, ACAT
      1, LIPG and PCSK9), DBP (ACAT-1, LDL-R, LIPC, PCSK9 and PPARD), and PP (LIPC,
      LIPG, MTHFR and PCSK9) in smokers were different among the genotypes (P < 0.01
      0.001). The SNPs of ABCA-1, ACAT-1 and PCSK9; ACAT-1, LDL-R, MTHFR and PCSK9; and
      ABCA-1, LIPC, PCSK9 and PPARD were shown interactions with cigarette smoking to
      influence SBP, DBP and PP levels (P < 0.05-0.001); respectively. The differences
      in blood pressure levels between the nonsmokers and smokers might partly result
      from different interactions of several SNPs and cigarette smoking.

PMID- 22606048
TI  - Surf the post-translational modification network of p53 regulation.
AB  - Among the human genome, p53 is one of the first tumor suppressor genes to be
      discovered. It has a wide range of functions covering cell cycle control,
      apoptosis, genome integrity maintenance, metabolism, fertility, cellular
      reprogramming and autophagy. Although different possible underlying mechanisms
      for p53 regulation have been proposed for decades, none of them is conclusive.
      While much literature focuses on the importance of individual post-translational
      modifications, further explorations indicate a new layer of p53 coordination
      through the interplay of the modifications, which builds up a complex 'network'.
      This review focuses on the necessity, characteristics and mechanisms of the
      crosstalk among post-translational modifications and its effects on the precise
      and selective behavior of p53.

PMID- 22606052
TI  - Upper respiratory tract colonization by gram-negative rods in patients with
      chronic lymphocytic leukemia: analysis of risk factors.
AB  - The aim of the study was to assess the frequency and predisposing factors of
      colonization of upper respiratory tract by Gram-negative rods (GNRs) in chronic
      lymphocytic leukemia (CLL) patients. Antimicrobial susceptibility of the isolated
      strains was determined. A significantly higher frequency of GNR colonization in
      CLL patients was observed (36.7%) in comparison to healthy volunteers (8.3%). GNR
      isolates mainly belonged to the Enterobacteriaceae family. Three isolates of GNR
      demonstrating presence of AmpC beta-lactamases and one ESBL-producing strain were
      obtained from CLL patients. GNR colonization rate was higher among CLL patients
      with lower level of IgG in serum (P = 0.017), with higher number of neutrophils
      (P = 0.039) or higher number of lymphocytes in serum (P = 0.053). The longer the
      time elapsed since diagnosis, the higher the frequency of GNR colonization
      observed. Multivariate analysis showed importance of the Rai stage, number, and
      type of infections as independent predictors of GNR colonization in CLL patients.

PMID- 22606053
TI  - Genetic variation and population structure in Jamunapari goats using
      microsatellites, mitochondrial DNA, and milk protein genes.
AB  - Jamunapari, a dairy goat breed of India, has been gradually declining in numbers
      in its home tract over the years. We have analysed genetic variation and
      population history in Jamunapari goats based on 17 microsatellite loci, 2 milk
      protein loci, mitochondrial hypervariable region I (HVRI) sequencing, and three Y
      chromosomal gene sequencing. We used the mitochondrial DNA (mtDNA) mismatch
      distribution, microsatellite data, and bottleneck tests to infer the population
      history and demography. The mean number of alleles per locus was 9.0 indicating
      that the allelic variation was high in all the loci and the mean heterozygosity
      was 0.769 at nuclear loci. Although the population size is smaller than 8,000
      individuals, the amount of variability both in terms of allelic richness and gene
      diversity was high in all the microsatellite loci except ILST 005. The gene
      diversity and effective number of alleles at milk protein loci were higher than
      the 10 other Indian goat breeds that they were compared to. Mismatch analysis was
      carried out and the analysis revealed that the population curve was unimodal
      indicating the expansion of population. The genetic diversity of Y-chromosome
      genes was low in the present study. The observed mean M ratio in the population
      was above the critical significance value (Mc) and close to one indicating that
      it has maintained a slowly changing population size. The mode-shift test did not
      detect any distortion of allele frequency and the heterozygosity excess method
      showed that there was no significant departure from mutation-drift equilibrium
      detected in the population. However, the effects of genetic bottlenecks were
      observed in some loci due to decreased heterozygosity and lower level of M ratio.
      There were two observed genetic subdivisions in the population supporting the
      observations of farmers in different areas. This base line information on genetic
      diversity, bottleneck analysis, and mismatch analysis was obtained to assist the
      conservation decision and management of the breed.

PMID- 22606054
TI  - Efficacy of some botanical extracts against Trogoderma granarium in wheat grains
      with toxicity evaluation.
AB  - In an attempt to find alternative control methods for stored products insects,
      extracts of seven plant species (Cassia senna, Caesalpinia gilliesii, Thespesia
      populnea var. acutiloba, Chrysanthemum frutescens, Euonymus japonicus, Bauhinia
      purpurea, and Cassia fistula) were evaluated under laboratory conditions for
      their ability to protect wheat (Triticum spp.) grains against Trogoderma
      granarium insect. Moreover, gas chromatography-mass spectrometry (GC-MS) analysis
      was carried to identify the chemical components of the most effective plant
      extract against T. granarium. Furthermore, the safety of the most effective plant
      extract was evaluated with respect to biochemical and histological changes in
      treated rats relative to control. The results revealed that, the tested botanical
      extracts showed high efficiency against T. granarium with respect to mortality
      and progeny of the adults. C. senna was the most effective botanical extract
      against T. granarium. The GC-MS analysis of the most effective plant extract
      showed the presence of different bioactive compounds that is known by its
      insecticidal activity. The most effective plant extract showed no toxicity on
      treated rats relative to control with respect to biochemical and histological
      changes. The results suggest the ability of using these plant extracts for wheat
      grains protection as a safe alternative to insecticides.

PMID- 22606055
TI  - Impact of long-term forest enrichment planting on the biological status of soil
      in a deforested dipterocarp forest in Perak, Malaysia.
AB  - Deforestation leads to the deterioration of soil fertility which occurs rapidly
      under tropical climates. Forest rehabilitation is one of the approaches to
      restore soil fertility and increase the productivity of degraded areas. The
      objective of this study was to evaluate and compare soil biological properties
      under enrichment planting and secondary forests at Tapah Hill Forest Reserve,
      Perak after 42 years of planting. Both areas were excessively logged in the 1950s
      and left idle without any appropriate forest management until 1968 when
      rehabilitation program was initiated. Six subplots (20 m * 20 m) were established
      within each enrichment planting (F1) and secondary forest (F2) plots, after which
      soil was sampled at depths of 0-15 cm (topsoil) and 15-30 cm (subsoil). Results
      showed that total mean microbial enzymatic activity, as well as biomass C and N
      content, was significantly higher in F1 compared to F2. The results, despite
      sample variability, suggest that the rehabilitation program improves the soil
      biological activities where high rate of soil organic matter, organic C, N,
      suitable soil acidity range, and abundance of forest litter is believed to be the
      predisposing factor promoting higher population of microbial in F1 as compared to
      F2. In conclusion total microbial enzymatic activity, biomass C and biomass N
      evaluation were higher in enrichment planting plot compared to secondary forest.
      After 42 years of planting, rehabilitation or enrichment planting helps to
      restore the productivity of planted forest in terms of biological parameters.

PMID- 22606056
TI  - Analysis of risk factors for amputation in 822 cases with acute arterial emboli.
AB  - BACKGROUND: We retrospectively examined the records of 822 patients who underwent
      a total of 901 operations for acute peripheral arterial occlusion of the upper or
      lower extremities between 1999 and 2009. We analyzed the effects of
      atherosclerotic structure, the time of admission to hospital, and re
      embolectomies on amputation in the early postoperative period. METHODS: There
      were 466 (56.7%) men and 356 (43.3%) women. The time of admission to hospital was
      in the range of 58 hours. There were lower extremity emboli in 683 (83%). Bypass
      procedures were done in 27 (3.3%) patients. Fasciotomy, patchplasty, and
      endarterectomy were made in 19 (2.3%), 9 (1.1%), and 7 (0.8%) patients,
      respectively. RESULTS: Early revision (re-embolectomy) was performed in 77 (9.3%)
      patients. Amputation was performed in 112 (13.6%) patients. Delay after six hours
      from the onset of complaints and re-embolectomies increased the risk of
      amputation and rates. CONCLUSION: If the embolectomy, which is a rapid and easy
      technique for treatment of acute arterial emboli, is performed by experienced
      surgeons without delay, the complications associated with the emboli may be
      prevented. Otherwise, delayed operation and repeated re-embolizations in acute
      arterial play important roles in morbidity.

PMID- 22606057
TI  - Ill, itinerant, and insured: the top 20 users of emergency departments in
      Baltimore city.
AB  - The purpose of this study was to document the clinical and demographic
      characteristics of the 20 most frequent users of emergency departments (EDs) in
      one urban area. We reviewed administrative records from three EDs and two
      agencies providing services to homeless people in Baltimore City. The top 20
      users accounted for 2,079 visits at the three EDs. Their mean age was 48, and
      median age was 51. Nineteen patients visited at least 2 EDs, 18 were homeless,
      and 13 had some form of public insurance. The vast majority of visits (86%) were
      triaged as moderate or high acuity. The five most frequent diagnoses were limb
      pain (n = 9), lack of housing (n = 6), alteration of consciousness (n = 6),
      infection with human immunodeficiency virus (HIV) (n = 5), and nausea/vomiting (n
      = 5). Hypertension, HIV infection, diabetes, substance abuse, and alcohol abuse
      were the most common chronic illnesses. The most frequent ED users were
      relatively young, accounted for a high number of visits, used multiple EDs, and
      often received high triage scores. Homelessness was the most common
      characteristic of this patient group, suggesting a relationship between this
      social factor and frequent ED use.

PMID- 22606058
TI  - Trace metal content of sediments close to mine sites in the Andean region.
AB  - This study is a preliminary examination of heavy metal pollution in sediments
      close to two mine sites in the upper part of the Jequetepeque River Basin, Peru.
      Sediment concentrations of Al, As, Cd, Cu, Cr, Fe, Hg, Ni, Pb, Sb, Sn, and Zn
      were analyzed. A comparative study of the trace metal content of sediments shows
      that the highest concentrations are found at the closest points to the mine sites
      in both cases. The sediment quality analysis was performed using the threshold
      effect level of the Canadian guidelines (TEL). The sediment samples analyzed show
      that potential ecological risk is caused frequently at both sites by As, Cd, Cu,
      Hg, Pb, and Zn. The long-term influence of sediment metals in the environment is
      also assessed by sequential extraction scheme analysis (SES). The availability of
      metals in sediments is assessed, and it is considered a significant threat to the
      environment for As, Cd, and Sb close to one mine site and Cr and Hg close to the
      other mine site. Statistical analysis of sediment samples provides a
      characterization of both subbasins, showing low concentrations of a specific set
      of metals and identifies the main characteristics of the different pollution
      sources. A tentative relationship between pollution sources and possible
      ecological risk is established.

PMID- 22606059
TI  - Computational methods to work as first-pass filter in deleterious SNP analysis of
      alkaptonuria.
AB  - A major challenge in the analysis of human genetic variation is to distinguish
      functional from nonfunctional SNPs. Discovering these functional SNPs is one of
      the main goals of modern genetics and genomics studies. There is a need to
      effectively and efficiently identify functionally important nsSNPs which may be
      deleterious or disease causing and to identify their molecular effects. The
      prediction of phenotype of nsSNPs by computational analysis may provide a good
      way to explore the function of nsSNPs and its relationship with susceptibility to
      disease. In this context, we surveyed and compared variation databases along with
      in silico prediction programs to assess the effects of deleterious functional
      variants on protein functions. In other respects, we attempted these methods to
      work as first-pass filter to identify the deleterious substitutions worth
      pursuing for further experimental research. In this analysis, we used the
      existing computational methods to explore the mutation-structure-function
      relationship in HGD gene causing alkaptonuria.

PMID- 22606060
TI  - Is there an association between socioeconomic status and body mass index among
      adolescents in Mauritius?
AB  - There are no documented studies on socioeconomic status (SES) and body mass index
      (BMI) among Mauritian adolescents. This study aimed to determine the
      relationships between SES and BMI among adolescents with focus on diet quality
      and physical activity (PA) as mediating factors. Mauritian school adolescents (n
      = 200; 96 males, 104 females) were recruited using multistage sampling.
      Participants completed a self-reported questionnaire. Height and weight were
      measured and used to calculate BMI (categorised into underweight, healthy-weight,
      overweight, obese). Chi-square test, Pearson correlation, and Independent samples
      t-test were used for statistical analysis. A negative association was found
      between SES and BMI (chi(2) = 8.15%, P < 0.05). Diet quality, time spent in PA at
      school (P = 0.000), but not total PA (P = 0.562), were significantly associated
      with high SES. Poor diet quality and less time spent in PA at school could
      explain BMI discrepancies between SES groups.

PMID- 22606062
TI  - Source apportionment of particle bound polycyclic aromatic hydrocarbons at an
      industrial location in Agra, India.
AB  - 16 U.S. EPA priority polycyclic aromatic hydrocarbons (PAHs) were quantified in
      total suspended ambient particulate matter (TSPM) collected from an industrial
      site in Agra (India) using gas chromatography. The major industrial activities in
      Agra are foundries that previously used coal and coke as fuel in cupola furnaces.
      These foundries have now switched over to natural gas. In addition, use of
      compressed natural gas has also been promoted and encouraged in automobiles. This
      study attempts to apportion sources of PAH in the ambient air and the results
      reflect the advantages associated with the change of fuel. The predominant PAHs
      in TSPM include high molecular weight (HMW) congeners BghiP, DbA, IP, and BaP.
      The sum of 16 priority PAHs had a mean value of 72.7 +/- 4.7 ng m(-3). Potential
      sources of PAHs in aerosols were identified using diagnostic ratios and principal
      component analysis. The results reflect a blend of emissions from diesel and
      natural gas as the major sources of PAH in the city along with contribution from
      emission of coal, coke, and gasoline.

PMID- 22606061
TI  - Genetic aspects of gastric cancer instability.
AB  - Unravelling the molecular mechanisms underlying gastric carcinogenesis is one of
      the major challenges in cancer genomics. Gastric cancer is a very complex and
      heterogeneous disease, and although much has been learned about the different
      genetic changes that eventually lead to its development, the detailed mechanisms
      still remain unclear. Malignant transformation of gastric cells is the
      consequence of a multistep process involving different genetic and epigenetic
      changes in numerous genes in combination with host genetic background and
      environmental factors. The majority of gastric adenocarcinomas are characterized
      by genetic instability, either microsatellite instability (MSI) or chromosomal
      instability (CIN). It is believed that chromosome destabilizations occur early in
      tumour progression. This review summarizes the most common genetic alterations
      leading to instability in sporadic gastric cancers and its consequences.

PMID- 22606063
TI  - A prospective study evaluating IOP changes after switching from a therapy with
      prostaglandin eye drops containing preservatives to nonpreserved tafluprost in
      glaucoma patients.
AB  - PURPOSE: To compare the ocular hypotensive effect of tafluprost with
      prostaglandin analogues (PGAs) in glaucoma patients. METHODS: 89 primary open
      angle glaucoma patients treated with bimatoprost, latanoprost, or travoprost for
      at least 3 months complaining for ocular discomfort were switched to tafluprost.
      IOP was assessed at baseline and 3 months after switching the therapy by daily
      curve. Primary outcome was to compare the mean daily IOP of tafluprost with PGAs.
      RESULTS: The mean daily IOP was 16 +/- 2.1 and 16.6 +/- 2.0 mm Hg at baseline and
      after switching to tafluprost, respectively (P > 0.05). When analysis was carried
      out between tafluprost and each previous PGAs, the comparison between latanoprost
      and tafluprost and travoprost and tafluprost did not show any statistically
      significant difference in mean daily IOP and at each time point. The comparison
      between bimatoprost and tafluprost showed a statistically significant difference
      in mean daily IOP (P < 0.05) and at each time point (P < 0.05). CONCLUSIONS:
      After 3 months of switching tafluprost showed an overall IOP lowering effect
      similar to others PGAs. When each PGA was compared with tafluprost, bimatoprost
      showed to provide a statistically significant additional IOP lowering effect.

PMID- 22606064
TI  - A randomized comparative trial on the therapeutic efficacy of topical aloe vera
      and Calendula officinalis on diaper dermatitis in children.
AB  - INTRODUCTION: Diaper dermatitis (DD) is a common inflammatory disorder among
      children and infants. The objective of the present randomized and double-blind
      trial was to compare the therapeutic efficacies of aloe vera cream and Calendula
      officinalis ointment on the frequency and severity of DD in children. METHODS:
      Sixty-six infants with DD (aged < 3 years) were randomized to receive either aloe
      cream (n = 32) or Calendula ointment (n = 34). Infants were treated with these
      drugs 3 times a day for 10 days. The severity of dermatitis was graded at
      baseline as well as at the end of trial using a 5-point scale. The adverse
      effects of study medications were assessed during the trial. RESULTS: Although
      improvement in the severity of DD was observed in both treatment groups (P <
      0.001), patients receiving Calendula ointment had significantly fewer rash sites
      compared to aloe group (P = 0.001). No adverse effect was reported from either of
      the medications. DISCUSSION: The evidence from this study suggests that topical
      aloe and in particular Calendula could serve as safe and effective treatment for
      the treatment of diaper dermatitis in infants.

PMID- 22606065
TI  - Stress studies of tenofovir disoproxil fumarate by HPTLC in bulk drug and
      pharmaceutical formulation.
AB  - A stability-indicating high-performance thin-layer chromatographic (HPTLC) method
      for determination of tenofovir disoproxil fumarate in bulk drug and in tablet has
      been developed and validated. The mobile phase selected was chloroform:methanol
      (9.0:1.0, v/v) with ultraviolet (UV) detection at 260 nm. The retention factor
      was found to be 0.49 +/- 0.03 with correlation coefficients of 0.9994 in the
      range 300-1500 ng/spot and with an accuracy of 99.25%. Method had the potential
      to determine tenofovir disoproxil fumarate from tablet without any interference,
      and it was a stability-indicating one.

PMID- 22606067
TI  - Studies on early allergic sensitization in the Lithuanian birth cohort.
AB  - Cohort studies are of great importance in defining the mechanism responsible for
      the development of allergy-associated diseases, such as atopic dermatitis,
      allergic asthma, and allergic rhinoconjunctivitis. Although these disorders share
      genetic and environmental risk factors, it is still under debate whether they are
      linked or develop sequentially along an atopic pathway. The current study was
      aimed to determine the pattern of allergy sensitization in the Lithuanian birth
      cohort "Alergemol" (n = 1558) established as a part of the multicenter European
      birth cohort "EuroPrevall". Early sensitization to food allergens in the
      "Alergemol" birth cohort was analysed. The analysis revealed 1.3% and 2.8% of
      symptomatic-sensitized subjects at 6 and 12 months of age, respectively. The
      sensitization pattern in response to different allergens in the group of infants
      with food allergy symptoms was studied using allergological methods in vivo and
      in vitro. The impact of maternal and environmental risk factors on the early
      development of food allergy in at 6 and 12 months of age was evaluated. Our data
      showed that maternal diet, diseases, the use of antibiotics, and tobacco smoke
      during pregnancy had no significant impact on the early sensitization to food
      allergens. However, infants of atopic mothers were significantly more often
      sensitized to egg as compared to the infants of nonatopic mothers.

PMID- 22606066
TI  - Do beta-defensins and other antimicrobial peptides play a role in neuroimmune
      function and neurodegeneration?
AB  - It is widely accepted that the brain responds to mechanical trauma and
      development of most neurodegenerative diseases with an inflammatory sequelae that
      was once thought exclusive to systemic immunity. Mostly cationic peptides, such
      as the beta-defensins, originally assigned an antimicrobial function are now
      recognized as mediators of both innate and adaptive immunity. Herein supporting
      evidence is presented for the hypothesis that neuropathological changes
      associated with chronic disease conditions of the CNS involve abnormal expression
      and regulatory function of specific antimicrobial peptides. It is also proposed
      that these alterations exacerbate proinflammatory conditions within the brain
      that ultimately potentiate the neurodegenerative process.

PMID- 22606068
TI  - The clinical and nonclinical values of nonexercise estimation of cardiovascular
      endurance in young asymptomatic individuals.
AB  - Exercise testing is associated with barriers prevent using cardiovascular (CV)
      endurance (CVE) measure frequently. A recent nonexercise model (NM) is alleged to
      estimate CVE without exercise. This study examined CVE relationships, using the
      NM model, with measures of obesity, physical fitness (PF), blood glucose and
      lipid, and circulation in 188 asymptomatic young (18-40 years) adults. Estimated
      CVE correlated favorably with measures of PF (r = 0.4 - 0.5) including handgrip
      strength, distance in 6 munities walking test, and shoulder press, and leg
      extension strengths, obesity (r = 0.2 - 0.7) including % body fat, body water
      content, fat mass, muscle mass, BMI, waist and hip circumferences and waist/hip
      ratio, and circulation (r = 0.2 - 0.3) including blood pressures, blood flow,
      vascular resistance, and blood (r = 0.2 - 0.5) profile including glucose, total
      cholesterol, LDL-C, HDL-C, and triglycerides. Additionally, differences (P <
      0.05) in examined measures were found between the high, average, and low
      estimated CVE groups. Obviously the majority of these measures are CV disease
      risk factors and metabolic syndrome components. These results enhance the NM
      scientific value, and thus, can be further used in clinical and nonclinical
      settings.

PMID- 22606069
TI  - Examination of the Predictors of Latent Class Typologies of Bullying Involvement
      among Middle School Students.
AB  - This study employs latent class analysis to construct bullying involvement
      typologies among 3114 students (48% male, 58% White) in 40 middle schools across
      the U.S. Four classes were constructed: victims (15%); bullies (13%); bully
      victims (13%); and noninvolved (59%). Respondents who were male and participated
      in fewer conventional activities were more likely to be members of the victims
      class. Students who were African-American and reported being less successful at
      school had a higher likelihood of membership in the bullies class. Bully-victims
      shared characteristics with bullies and victims: Students with more feelings of
      anger toward others and a higher tendency toward sensation-seeking had a higher
      likelihood of membership in the bullies and bully-victims classes, whereas lower
      levels of social inclusion was associated with membership in the victims and
      bully-victims classes.

PMID- 22606072
TI  - They're Here ... Now!

PMID- 22606071
TI  - Improving MM-GB/SA Scoring through the Application of the Variable Dielectric
      Model.
AB  - A variable dielectric model based on residue types for better description of
      protein-ligand electrostatics in MM-GBSA scoring is reported. The variable
      dielectric approach provides better correlation with binding data and reduces the
      score dynamic range, typically observed in the standard MM-GB/SA method. The
      latter supports the view that exaggerated enthalpic separation between weak and
      potent compounds due to the lack of shielding effects in the model is greatly
      responsible for the wide scoring spread.

PMID- 22606073
TI  - Clinical trials, research, and FDA findings.

PMID- 22606074
TI  - Finding the Right Formula for Bundled Payments: Could reimbursements edge out
      biologics?

PMID- 22606075
TI  - PBM Consolidation: Better Pricing or Just Less Competition?: The growth of
      specialty pharmaceuticals, including biologics, is forcing payers and employers
      to look at cost-saving strategies for managing those drugs. How will they do it
      if only one large PBM rules the specialty pharmacy network?
AB  - While the ramifications of Express Scripts' planned takeover of Medco are being
      debated, the use of pharmacy benefit managers is being questioned as cost savings
      decline and transparency issues hang high. And payers and employers still can't
      get rid of a "bad taste in the mouth." So what does a mega PBM hope to
      accomplish?

PMID- 22606076
TI  - A conversation with cheryl larson: vice president, midwest business group on
      health.
AB  - By 2017, 40 percent of medical spend will be on biologics. It's time for
      employers to learn how to manage these drugs.

PMID- 22606077
TI  - In Search of the Perfect Business Model: As personalized medicine moves into the
      mainstream, makers of diagnostics must face a new economic reality. How to
      develop a value proposition in a healthcare market that is becoming increasingly
      elastic?
AB  - As personalized medicine edges toward the mainstream, economic realities threaten
      its existence. But without companion diagnostics, "getting the right drug to the
      right person" could wind up being just a slogan. What's the right business model?

PMID- 22606070
TI  - Ovarian cancer and body size: individual participant meta-analysis including
      25,157 women with ovarian cancer from 47 epidemiological studies.
AB  - BACKGROUND: Only about half the studies that have collected information on the
      relevance of women's height and body mass index to their risk of developing
      ovarian cancer have published their results, and findings are inconsistent. Here,
      we bring together the worldwide evidence, published and unpublished, and describe
      these relationships. METHODS AND FINDINGS: Individual data on 25,157 women with
      ovarian cancer and 81,311 women without ovarian cancer from 47 epidemiological
      studies were collected, checked, and analysed centrally. Adjusted relative risks
      of ovarian cancer were calculated, by height and by body mass index. Ovarian
      cancer risk increased significantly with height and with body mass index, except
      in studies using hospital controls. For other study designs, the relative risk of
      ovarian cancer per 5 cm increase in height was 1.07 (95% confidence interval
      [CI], 1.05-1.09; p<0.001); this relationship did not vary significantly by
      women's age, year of birth, education, age at menarche, parity, menopausal
      status, smoking, alcohol consumption, having had a hysterectomy, having first
      degree relatives with ovarian or breast cancer, use of oral contraceptives, or
      use of menopausal hormone therapy. For body mass index, there was significant
      heterogeneity (p<0.001) in the findings between ever-users and never-users of
      menopausal hormone therapy, but not by the 11 other factors listed above. The
      relative risk for ovarian cancer per 5 kg/m(2) increase in body mass index was
      1.10 (95% CI, 1.07-1.13; p<0.001) in never-users and 0.95 (95% CI, 0.92-0.99;
      p=0.02) in ever-users of hormone therapy. CONCLUSIONS: Ovarian cancer is
      associated with height and, among never-users of hormone therapy, with body mass
      index. In high-income countries, both height and body mass index have been
      increasing in birth cohorts now developing the disease. If all other relevant
      factors had remained constant, then these increases in height and weight would be
      associated with a 3% increase in ovarian cancer incidence per decade. Please see
      later in the article for the Editors' Summary.

PMID- 22606078
TI  - Innovation and Competition: Will Biosimilars Succeed?: The creation of an FDA
      approval pathway for biosimilars is complex and fraught with hazard. Yes,
      innovation and market competition are at stake. But so are efficacy and patient
      safety.
AB  - Biosimilars are here, but there's no clear pathway yet for their approval.
      Difficult realities about their effect on drug prices, innovation, and
      competition need to be faced.

PMID- 22606079
TI  - Saving dollars, preventing disappointment.

PMID- 22606080
TI  - Biotechnology Healthcare's 2011 Editorial Index.

PMID- 22606081
TI  - Oncology costs must be reined in, say payers.

PMID- 22606082
TI  - A redetermination of the structure of poly[[MU(4)-(R)-2-ammonio-3-sulfonato
      propano-ato]aqua-sodium], originally reported as poly[[MU(7)-l-cysteato(2
      )]disodium].
AB  - The structure originally reported as poly[[MU(7)-l-cysteato(2-)]disodium],
      [Na(2)(C(3)H(5)NO(5)S)](n) [Liu (2002). Acta Cryst. E67, m1346-m1347], has been
      redetermined with one of the sodium atoms replaced with a water mol-ecule and an
      additional proton attached to the amine group, resulting in the revised formula
      [Na{CO(2)CH(CH(2)SO(3))NH(3)}(H(2)O)](n). The agreement index, wR, has been
      reduced from 0.159 to 0.087 and the global instability index from 0.56 vu
      (valence units) to the acceptable value of 0.11 vu.

PMID- 22606083
TI  - N-(3-Bromo-2-methyl-phen-yl)-2-oxo-1,2-di-hydro-pyridine-3-carboxamide.
AB  - The title compound, C(13)H(11)BrN(2)O(2), consists of two six-membered rings
      linked by an amide group and adopts a near planar conformation. The dihedral
      angle between the two rings is 8.38 (11) degrees . In the crystal structure,
      there are intra- and inter-molecular N-H?O hydrogen bonds, the latter forming
      inversion dimers.

PMID- 22606084
TI  - (E)-2-(2,3-Dimethyl-anilino)-N'-[2-methyl-5-(prop-1-en-2-yl)cyclo-hex-2-enyl
      idene]benzohydrazide.
AB  - The asymmetric unit of the title compound, C(25)H(29)N(3)O, comprises two
      crystallographically independent mol-ecules. The dihedral angles between the
      benzene rings in the two mol-ecules are 59.7 (2) and 61.27 (18) degrees . The
      cyclo-hexene rings adopt sofa and half-chair conformations. In the crystal, mol
      ecules are connected via N-H?O and weak C-H?O hydrogen bonds, forming chains
      along the a axis. In each mol-ecule, there is an intra-molecular N-H?O hydrogen
      bond.

PMID- 22606085
TI  - N-(2-Amino-pyridin-3-yl)-4-methyl-N-(4-methyl-phenyl-sulfon-yl)benzene
      sulfonamide.
AB  - The title compound, C(19)H(19)N(3)O(4)S(2), was prepared by the reaction of 2,3
      diamino-pyridine with tosyl chloride in a mixture of dichloro-methane-pyridine as
      solvent. In the crystal, mol-ecules associate via pairs of N-H?N hydrogen bonds,
      forming a centrosymmetric eight-membered {?HNCN}(2) synthon. The dihedral angles
      between the amino-pyridine ring and the tosyl benzene rings are 50.01 (6) and
      32.01 (4) degrees .

PMID- 22606086
TI  - 3',4'-Dimeth-oxy-biphenyl-4-carbonitrile.
AB  - The title compound, C(15)H(13)NO(2), was prepared through a palladium-catalysed
      Suzuki-Miyaura coupling reaction. The dihedral angle between the biphenyl rings
      is 40.96 (6) degrees . The meth-oxy groups are twisted slightly out of the plane
      of the benzene ring [C-C-C-C torsion angles = -3.61 (18) and 12.6 (2) degrees ].
      The packing of the molecules is stabilized by van der Waals inter-actions.

PMID- 22606087
TI  - (2S,3R)-tert-Butyl N-[4-(N-benzyl-4-fluoro-benzene-sulfonamido)-3-hy-droxy-1
      phenyl-butan-2-yl]carbamate.
AB  - In the title mol-ecule, C(28)H(33)FN(2)O(5)S, the mean plane about the tertiary
      amine group (sum of the angles subtended at the sp(2)-hybridized N atom = 359.7
      degrees ) forms a dihedral angle of 16.66 (6) degrees  with the phenyl ring
      adjacent to the carbamate group. The sulfonamide benzene ring and the hy-droxy
      group lie to either side of the C(2)NS plane, whereas the benzyl-phenyl
      (connected to the N atom) and carbamate substituents lie to the other side. Supra
      molecular layers propagating in the ac plane are found in the crystal, linked by
      hy-droxy-sulfonamide O-H?O and carbamate-carbamate N-H?O hydrogen bonds along
      with C-H?O and C-H?pi inter-actions.

PMID- 22606088
TI  - 2-(4-Sulfamoylphen-yl)hydrazin-1-ium chloride.
AB  - The hydrazinium residue in the cation of the title salt,
      C(6)H(10)N(3)O(2)S(+).Cl(-), is twisted out of the plane of the benzene ring to
      which it is attached [N-N-C-C torsion angle = 25.9 (2) degrees ] and the amino
      group is almost perpendicular to the benzene ring [N-S-C-C torsion angle = 88.71
      (16) degrees ]. In the crystal, the cations are linked by N-H?O hydrogen bonds
      and pi-pi inter-actions [ring centroid distance = 3.7280 (11) A], forming layers
      in the bc plane that are connected by N-H?Cl hydrogen bonds.

PMID- 22606089
TI  - 2-[N-(4-{4-[(2-Hy-droxy-5-meth-oxy-benzyl-idene)amino]-benz-yl}phen
      yl)carboximido-yl]-4-meth-oxy-phenol.
AB  - In the title Schiff base, C(29)H(26)N(2)O(4), the complete molecule is generated
      by a crystallographic twofold axis and is V-shaped. The planes of the benzene
      rings of the central diphenyl-methane unit make a dihedral angle of 78.11 (4)
      degrees  while adjacent benzene and 5-meth-oxy-salicyl-idene rings are twisted
      with respect to each other by a dihedral angle of 11.84 (8) degrees . The Schiff
      base is in the enol-imino form and an intra-molecular O-H?N hydrogen bond is
      observed.

PMID- 22606090
TI  - 1-(2,4-Dichloro-phen-yl)-5-(2-nitro-anilino)-1H-pyrazole-4-carbonitrile.
AB  - In the title compound, C(16)H(9)Cl(2)N(5)O(2), the folded mol-ecular conformation
      is characterized by a dihedral angle between the two benzene rings of 74.03 (5)
      degrees . An intra-molecular N-H?O hydrogen bond is observed between the H atom
      of the amide group and a nitro-group O atom. Inter-molecular C-H?O and N-H?N
      hydrogen bonds feature in the crystal packing.

PMID- 22606091
TI  - (Z)-3-p-Tolyl-2-(p-tolyl-imino)-1,3-thia-zolidin-4-one.
AB  - In the title compound, C(17)H(16)N(2)OS, the central thia-zolidin-4-one ring
      forms dihedral angles of 66.49 (9) and 79.45 (6) degrees  with the two methyl
      substituted benzene rings. In the crystal, mol-ecules are stacked in columns
      along the b axis through C-H?pi inter-actions. The H atoms of one of the methyl
      groups are disordered over two orientations with equal site occupancies.

PMID- 22606092
TI  - N'-[(1E,2E)-3,7-Dimethyl-octa-2,6-dien-1-yl-idene]pyridine-4-carbohydrazide.
AB  - In the title compound, C(16)H(21)N(3)O, the mol-ecule adopts an E conformation
      about the central C=N double bond. The 2-methyl-pent-2-ene group is disordered
      over two sets of sites, with a refined occupancy ratio of 0.785 (8):0.215 (8).
      The dihedral angle between the essentially planar [the r.m.s. value for the major
      component is 0.021 (7) and its maximum deviation is 0.025 (4) A; the r.m.s. value
      for the minor component is 0.03 (4) and its maximum deviation is 0.05 (3) A]
      major and minor components of the 2-methyl-but-2-ene group is 35.9 (13) degrees .
      In the crystal, C-H?O and N-H?O hydrogen bonds link the molecules, with the same
      O atom acting as the acceptor. This results in C(1) (1)(4) and C(1) (1)(5) [001]
      chains.

PMID- 22606093
TI  - 2-Amino-6-{[(6-chloropyridin-3-yl)methyl](ethyl)amino}-1-methyl-5-nitro-4-phenyl
      1,4-dihydro-pyridine-3-carbonitrile ethanol monosolvate.
AB  - In the title compound, C(21)H(21)ClN(6)O(2).C(2)H(6)O, a member of the
      insecticidal active neonicotinoid group of compounds, the 1,4-dihydro-pyridine
      ring adopts a boat conformation. An intra-molecular C-H?O hydrogen bond occurs
      while the components are linked by an N-H?O interaction. The crystal packing is
      stablized by O-H?N hydrogen bonds and C-H?O interactions.

PMID- 22606094
TI  - (1S,2R,3R,6R,7S,8R,10S,11S)-13-{[4-(4-Chloro-phen-yl)piperazin-1-yl]meth-yl}-10
      hy-droxy-4,9-dimethyl-3,8,15-trioxatetra-cyclo-[10.3.0.0(2,4).0(7,9)]penta-decan
      14-one.
AB  - The title compound, C(25)H(33)ClN(2)O(5), was synthesized from 9alpha-hy-droxy
      parthenolide (9alpha-hy-droxy-4,8-dimethyl-12-methyl-ene-3,14-dioxatricyclo
      [9.3.0.0(2,4)]tetra-dec-7-en-13-one), which was isolated from the chloro-form
      extract of the aerial parts of Anvillea radiata. The mol-ecule is built up from
      fused five- and ten-membered rings with two additional ep-oxy ring systems and a
      chloro-phenyl-piperazine group as a substituent. The ten-membered ring adopts an
      approximate chair-chair conformation, while the piperazine ring displays a chair
      conformation and the five-membered ring shows an envelope conformation with the C
      atom closest to the hy-droxy group forming the flap. The mol-ecular conformation
      is stabilized by an intra-molecular O-H?N hydrogen bond between the hy-droxy
      group and a piperazine N atom. The crystal structure is stabilized by weak C-H?O
      inter-actions.

PMID- 22606095
TI  - 4-(4-Amino-2-fluoro-phen-oxy)-7-meth-oxy-quinazolin-6-ol methanol monosolvate.
AB  - In the title compound, C(15)H(12)FN(3)O(3).CH(3)OH, the dihedral angle between
      the quinazoline ring system and the benzene ring is 81.18 (9) degrees . In the
      crystal, mol-ecules are linked by N-H?O and O-H?N hydrogen bonds, generating [10
      1] chains of alternating main mol-ecules and solvent mol-ecules. Weak C-H?O inter
      actions are also observed.

PMID- 22606096
TI  - 2-Chloro-N-[3-cyano-1-(3,4-dichloro-phen-yl)-1H-pyrazol-5-yl]acetamide.
AB  - In the title compound, C(12)H(7)Cl(3)N(4)O, the dihedral angle between the
      pyrazole and benzene rings is 35.6 (3) degrees . In the crystal, mol-ecules are
      linked by N-H?O hydrogen bonds generating C(4) chains propagating in [100].

PMID- 22606097
TI  - 1-(2-Methyl-benz-yl)-1H-indole-3-carbaldehyde.
AB  - In the title compound, C(17)H(15)NO, the benzene ring and the indole system are
      almost perpendicular, making a dihedral angle of 87.82 (6) degrees . The crystal
      packing is stabilized by C-H?O and pi-pi stacking inter-actions with centroid
      centroid distances of 3.592 (4) A between the pyrrole and the benzene rings in
      the indole systems of neighboring mol-ecules.

PMID- 22606098
TI  - Methyl 2,2-dimeth-oxy-8-oxo-1-oxaspiro-[4.5]deca-6,9-diene-3-carboxyl-ate.
AB  - In the title mol-ecule, C(13)H(16)O(6), the cyclo-hexa-1,4-diene ring adopts a
      flat boat conformation (r.m.s. deviation from planarity = 0.060 A) and the five
      membered tetra-hydro-furan ring adopts an envelope conformation with the carboxyl
      group-substituted C atom as the flap. The dihedral angle at the spiro junction is
      89.1 (1) degrees . In the crystal, mol-ecules are linked through weak C-H?O and
      van der Waals inter-actions.

PMID- 22606099
TI  - 1-[(2S)-1-Chloro-3-phenyl-propan-2-yl]-2,4,5-triphenyl-1H-imidazole.
AB  - In the title compound, C(30)H(25)ClN(2), the chiral center maintains the S
      configuration of the stating l-phenyl-alaninol. The two phenyl groups closest to
      the substituted N atom adopt an almost perpendicular orientation relative to the
      central imidazole ring, with dihedral angles of 88.9 (4) and 84.7 (3) degrees .
      The third phenyl group is nearly coplanar with it, making a dihedral angle of
      11.0 (5) degrees .

PMID- 22606100
TI  - (4Z)-4-Benzyl-idene-2-phenyl-1,3-oxazol-5(4H)-one.
AB  - In the title compound, C(17)H(13)NO(2), the benzene ring is twisted slightly out
      of the plane of the oxazole ring to which it is attached [dihedral angle = 7.98
      (8) degrees ]. Similarly, there is a twist [dihedral angle = 5.50 (8) degrees ]
      between the oxazole and phenyl rings that are linked via the C=C bond [1.348 (2)
      A]; the conformation about the latter is Z. In the crystal, the presence of C
      H?O, C-H?pi and pi-pi inter-actions [centroid-centroid distance = 3.5259 (9) A]
      link the mol-ecules into a three-dimensional architecture.

PMID- 22606101
TI  - N-(4-Sulfamoylphen-yl)acetamide.
AB  - In the title compound, C(8)H(10)N(2)O(3)S, the dihedral angle between the
      acetamide group and the benzene ring is 15.59 (12) degrees  and the amino group
      is close to being perpendicular to the benzene ring [N-S-C(ar)-C(ar) (ar =
      aromatic) torsion angle = 109.4 (2) degrees ]. In the crystal, mol-ecules are
      linked into supra-molecular tubes parallel to [001] by amine-amide N-H?O inter
      actions and these are connected into the three-dimensional architecture by amide
      sulfonamide N-H?O hydrogen bonds. The crystal studied was a racemic twin.

PMID- 22606102
TI  - 4-[(1,3-Thia-zol-2-yl)sulfamo-yl]phenyl 2,2,2-trifluoro-acetate.
AB  - In the title compound, C(11)H(7)F(3)N(2)O(4)S(2), the 1,3-thia-zol-2-amine
      residue is almost perpendicular to the central benzene ring [dihedral angle =
      84.3 (2) degrees ]. There is a small twist between the benzene ring and the ester
      group [C-O-C-C torsion angle = 9.8 (6) degrees ]. Thus, the mol-ecule has an L
      shape. Inversion-related dimers are connected in the crystal packing by pairs of
      N-H?N hydrogen bonds formed between the amine H and thia-zole N atom via eight
      membered {?HNCN}(2) synthons.

PMID- 22606103
TI  - A second monoclinic polymorph for 3-amino-1-(4-meth-oxy-phen-yl)-9,10-dihydro
      phenanthrene-2,4-dicarbonitrile.
AB  - The title compound, C(23)H(17)N(3)O, has been previously described in a
      monoclinic P2(1)/c polymorph with Z = 4 [Asiri, Al-Youbi, Faidallah, Ng & Tiekink
      (2011). Acta Cryst. E67, o2449]. In the new monoclinic P2(1)/n form, with Z = 8,
      there are two independent mol-ecules, A and B, in the asymmetric unit. In both
      mol-ecules, the cyclo-hexa-1,3-diene ring has a screw-boat conformation, whereas
      it is a distorted half-chair in the original polymorph. There is a fold in each
      mol-ecule, as indicated by the dihedral angle between the benzene rings of the
      1,2-dihydro-naphthalene and aniline residues of 33.19 (10) degrees  (mol-ecule A)
      and 30.6 (10) degrees  (mol-ecule B). The meth-oxy-benzene ring is twisted out of
      the plane of the aniline residue to which it is connected [dihedral angles =
      49.22 (10) and 73.27 (10) degrees , in A and B respectively]. In the crystal, the
      two independent mol-ecules self-associate via N-H?N hydrogen bonds, generating a
      12-membered {?HNC(3)N}(2) synthon. These are connected into a supra-molecular
      tape in the (-101) plane by N-H?O(meth-oxy) inter-actions. In the P2(1)/c
      polymorph, supra-molecular layers are formed by N-H?N and N-H?O inter-actions.

PMID- 22606104
TI  - Bis(adamantan-1-aminium) carbonate.
AB  - In the title compound, 2C(10)H(18)N(+).CO(3) (2-), the adamantan-1-aminium cation
      forms three N-H?O hydrogen bonds to three carbonate ions, resulting in a layer
      parallel to (001) with the adamantane groups located on its surface so that
      adjacent layers form only C-H?H-C contacts. The carbonate anions occupy special
      positions of 32 symmetry, whereas the adamantan-1-aminium cations occupy special
      positions of 3 symmetry.

PMID- 22606106
TI  - 7-Chloro-5-(chloro-meth-yl)pyrazolo-[1,5-a]pyrimidine-3-carbonitrile.
AB  - All non-H atoms of the title compound, C(8)H(4)Cl(2)N(4), are essentially
      coplanar, with an r.m.s. deviation of 0.011 A. In the crystal, weak C-H?N
      hydrogen bonds link the mol-ecules into infinite sheets parallel to the bc plane.

PMID- 22606105
TI  - 3-Acetyl-1-(2-methylphenyl)thiourea.
AB  - In the title compound, C(10)H(12)N(2)OS, the toluene and the N-carbamothio
      ylacetamide units are oriented at dihedral angle of 78.75 (5) degrees . An intra
      molecular N-H?O hydrogen bond generates an S(6) ring. In the crystal, mol-ecules
      are linked into [101] chains by pairs of N-H?S hydrogen bonds [which generate
      R(2) (2)(8) loops] and pairs of O-H?O hydrogen bonds [which generate R(2) (2)(4)
      loops]. The two motifs alternate in the chain.

PMID- 22606107
TI  - 1-(2-Hy-droxy-eth-yl)-3-phenyl-thio-urea.
AB  - The title compound, C(9)H(12)N(2)OS, was obtained unexpectedly in a
      multicomponent reaction of an equimolar ratio of phenyl isothio-cyanate,
      malononitrile and amino-ethanol. The -C(H(2))-N(H)-(C=S)-N(H)- methyl-thio-urea
      methane group is almost normal to the phenyl ring, with a dihedral angle of 71.13
      (9) degrees . The N-C-C-O torsion angle is 72.8 (2) degrees . In the crystal, mol
      ecules are connected by N-H?O, O-H?S and N-H?O hydrogen bonds, forming a three
      dimensional network.

PMID- 22606108
TI  - (2E)-1-(2,6-Dichloro-3-fluoro-phen-yl)-3-(4-meth-oxy-phen-yl)prop-2-en-1-one.
AB  - There are two independent mol-ecules in the asymmetric unit of the title
      compound, C(16)H(11)Cl(2)FO(2). The F atom equally populates both meta positions
      of the 6-dichloro-3-fluoro-phenyl ring in each mol-ecule, resulting in 0.5
      occupancy for both the F and H atoms in these positions. The dihedral angle
      between the mean planes of the benzene rings are 77.5 (2) and 89.8 (8) degrees in
      the two mol-ecules. In the crystal, weak C-H?F and C-H?O inter-actions involving
      the half-occupied H and F atoms are observed. Weak pi-pi stacking inter-actions
      [centroid-centroid distance = 3.150 (2) A] also contribute to the crystal
      stability.

PMID- 22606109
TI  - 2-Fluoro-N'-[(2-meth-oxy-naphthalen-1-yl)methyl-idene]benzohydrazide.
AB  - The asymmetric unit of the title compound, C(19)H(15)FN(2)O(2), contains two mol
      ecules, A and B, in which the dihedral angles between the ring systems are 46.4
      (2) and 17.24 (14) degrees , respectively. In the crystal, mol-ecules are linked
      into [010] chains of alternating A and B species by N-H?O hydrogen bonds.

PMID- 22606110
TI  - Cinnarizinium 3,5-dinitro-salicylate.
AB  - THE TITLE COMPOUND [SYSTEMATIC NAME: 4-diphenyl-methyl-1-(3-phenylprop-2-en-1-yl)
      piperazin-1-ium 2-carb-oxy-4,6-dinitro-pheno-late], C(26)H(29)N(2)
      (+).C(7)H(3)N(2)O(7) (-), is the dinitro-salicylate salt of a tertiary amine.
      Deprotonation of the carb-oxy-lic acid group occurred on the phenolic hy-droxy
      group. The diaza-cyclo-hexane ring adopts a chair conformation. Intra-molecular O
      H?O and inter-molecular C-H?O and N-H?O hydrogen bonds are observed. The N-H?O
      hydrogen bonds are bifurcated at the H atom and connect the cinnarizinium and 3,5
      dinitro-salicylate ions together. Inter-molecular C-H?O hydrogen bonds connect
      the components into layers perpendicular to the crystallographic a axis.

PMID- 22606111
TI  - 3-Acetyl-5-phenyl-1-p-tolyl-1H-pyrazole-4-carbonitrile.
AB  - In the title pyrazole derivative, C(19)H(15)N(3)O, the central pyrazole ring
      makes dihedral angles of 42.71 (9) and 61.34 (9) degrees , respectively, with the
      phenyl and p-tolyl rings. The dihedral angle between the phenyl and p-tolyl rings
      is 58.22 (9) degrees . The 3-acetyl-1H-pyrazole-4-carbonitrile unit is
      essentially planar, with an r.m.s. deviation of 0.0295 (1) A for the ten non-H
      atoms.

PMID- 22606112
TI  - 4-[5-(Furan-2-yl)-3-trifluoro-methyl-1H-pyrazol-1-yl]benzene-sulfonamide.
AB  - In the title compound, C(14)H(10)F(3)N(3)O(3)S, there are significant twists in
      the mol-ecule, as seen in the values of the dihedral angles between the pyrazole
      ring and each of the furan [31.1 (2) degrees ] and benzene rings [55.58 (10)
      degrees ]. The amino N atom occupies a position almost normal to the benzene ring
      [N-S-C(ar)-C(ar) (ar = aromatic) torsion angle = 83.70 (19) degrees ]. One amino
      H atom forms a hydrogen bond to the tricoordinate pyrazole N atom and the other
      inter-acts with a sulfonamide O atom, forming a supra-molecular chain along
      [010]. The chains are consolidated into a supra-molecular layers via C-H?O inter
      actions involving the second sulfonamide O atom; layers stack along [10-1]. The
      furan ring was found to be disordered over two diagonally opposite orientations
      of equal occupancy.

PMID- 22606113
TI  - 2-[(1-Methyl-1H-pyrrol-2-yl)methyl-idene]propane-dinitrile.
AB  - In the title compound, C(9)H(7)N(3), the N-bound methyl group and vinyl H atom
      are syn. The 12 non-H atoms comprising the mol-ecule are essentially coplanar
      (r.m.s. deviation = 0.071 A). Supra-molecular tapes feature in the crystal
      packing, orientated perpendicular to [10-1], and are formed by C-H?N inter
      actions involving each cyano N atom. The tapes are connected into layers via pi
      pi inter-actions occurring between translationally related pyrrole rings [ring
      centroid-centroid distance = 3.8754 (10) A]; the layers stack along the b axis.

PMID- 22606114
TI  - 3-Oxapentane-1,5-diyl dicarbamate.
AB  - The complete mol-ecule of the title compound, C(6)H(12)N(2)O(5), is generated by
      a rotation about a twofold axis. The conformation along the bond sequence linking
      the two amino groups is trans-trans-(+)gauche-trans-trans. In the crystal, N-H?O
      hydrogen bonds link the mol-ecules into a three-dimensional supra-molecular
      architecture.

PMID- 22606115
TI  - 5-Chloro-spiro-[indoline-3,7'-6H,7H,8H-pyrano[3,2-c:5,6-c']di[1]benzopyran]
      2,6',8'-trione.
AB  - The asymmetric unit of the title compound, C(26)H(12)ClNO(6), consists of two
      independent mol-ecules. The central pyran rings and both the 1-benzopyran ring
      systems are nearly planar in both mol-ecules [r.m.s. deviations of pyan rings =
      0.0264 (1) and 0.0326 (1) A for molecules A and B, respectively; r.m.s.
      deviations of benzopyran rings = 0.0439 (1) and 0.0105 (1) for molecule A, 0.0146
      (1) and 0.0262 (1) A for molecule B]. In the crystal, the molecules are linked by
      C-H?O, N-H?O and C-H?pi inter-actions.

PMID- 22606116
TI  - 2-[(E)-(1,10-Phenanthrolin-5-yl)imino-meth-yl]phenol methanol monosolvate.
AB  - In the title multi-donor Schiff base compound, C(19)H(13)N(3)O.CH(3)OH, the
      dihedral angle between the mean planes of the phenanthroline and phenol rings is
      59.3 (1) degrees . The Schiff base mol-ecule is linked to the solvent mol-ecule
      by an O-H?O hydrogen bond. In the crystal, the components are linked by O-H?N
      hydrogen bonds, weak O-H?N inter-actions and pi-pi stacking inter-actions
      [centroid-centroid distances = 3.701 (1) and 3.656 (1) A].

PMID- 22606117
TI  - 4,4'-Bipyrid-yl-4,4'-(hy-droxy-methyl-ene)dibenzoic acid (1/1).
AB  - In the title 1:1 co-crystal, C(10)H(8)N(2).C(15)H(12)O(5), strong inter-molecular
      O-H?N hydrogen bonds link alternating mol-ecules of 4,4'-(hy-droxy-methyl
      ene)dibenzoic acid and 4,4'-bipyridyl into zigzag chains in [501]. The crystal
      packing also exhibits pi-pi inter-actions between the 4,4'-bipyridyl rings of
      neighbouring chains [centroid-centroid distance = 3.608 (3) A] and weak C-H?O
      hydrogen bonds.

PMID- 22606118
TI  - 6,6'-Dimeth-oxy-2,2'-[(E,E')-(2,4,6-trimethyl-1,3-phenyl-ene)bis-(nitrilo
      methanylyl-idene)]diphenol chloro-form monosolvate.
AB  - In the title compound, C(25)H(26)N(2)O(4).CHCl(3), the aromatic rings of the
      imino-methyl-6-meth-oxy-phenol fragments make dihedral angles of 58.33 (6) and
      87.74 (6) degrees  with the central benzene ring. The mol-ecular conformation is
      stabilized by intra-molecular O-H?N hydrogen bonds. In the crystal, an inter
      molecular C-H?O hydrogen bond involving the chloro-form solvent mol-ecule is
      observed. The crystal packing is further stabilized by pi-pi stacking inter
      actions [centroid-centroid distances = 3.739 (3)-3.776 (3) A] between the benzene
      rings of centrosymmetrically related mol-ecules.

PMID- 22606119
TI  - N-Acetyl-N-[2,4-dicyano-1-(4-meth-oxy-phen-yl)-9,10-dihydro-phenanthren-3
      yl]acetamide.
AB  - In the title compound, C(27)H(21)N(3)O(3), the cyclo-hexa-1,3-diene ring has a
      screw-boat conformation, and the fused ring system is folded, the dihedral angle
      between the outer benzene rings being 27.61 (6) degrees . The N-acetyl-acetamide
      residue (r.m.s. deviation = 0.0935 A) has an anti conformation and is essentially
      perpendicular to the benzene ring to which it is connected [dihedral angle =
      89.14 (6) degrees ]; the meth-oxy-benzene group is also twisted out of this ring
      [dihedral angle = 59.47 (7) degrees ]. The three-dimensional architecture is
      consolidated by C-H?O and C-H?pi inter-actions.

PMID- 22606120
TI  - 5,7,7,12,14,14-Hexamethyl-4,11-diaza-1,8-diazo-niacyclo-tetra-decane bis
      (perchlorate) monohydrate.
AB  - In the title hydrated salt, C(16)H(38)N(4) (2+).2ClO(4) (-).H(2)O, the dication
      is protonated at the diagonally opposite N atoms proximate to the -C(CH(3))(2)-
      groups. Within the cavity, there are two ammonium-amine N-H?N hydrogen bonds.
      Supra-molecular layers are formed in the crystal packing whereby the water mol
      ecule links two perchlorate anions, and the resultant aggregates are connected to
      the dications via N-H?O hydrogen bonds. Layers, with an undulating topology,
      stack along the a axis being connected by C-H?O inter-actions.

PMID- 22606121
TI  - 4-[Bis(4-fluoro-phen-yl)meth-yl]piperazin-1-ium 2-hy-droxy-benzoate 2-hy-droxy
      benzoic acid monosolvate.
AB  - The title compound, C(17)H(19)F(2)N(2) (+).C(7)H(5)O(3) (-).C(7)H(6)O(3), is a co
      crystal from 4-[bis-(4-fluoro-phen-yl)meth-yl]piperazin-1-ium, salicylate anion
      and salicylic acid in a 1:1:1 ratio. In addition to an intra-molecular O-H?O
      hydrogen bond, the crystal packing shows hydrogen bonds between the piperazinium
      cation and salicylate anion (N-H?O), as well as between the salicylic acid mol
      ecule and anion (O-H?O), giving rise to a three-dimensional network.

PMID- 22606122
TI  - (5-Bromo-2-hy-droxy-phen-yl)(4-propyl-cyclo-hex-yl)methanone.
AB  - In the title compound, C(16)H(21)BrO(2), the cyclo-hexane ring adopts a chair
      conformation. The hy-droxy and carbonyl groups are involved in an intra-molecular
      O-H?O hydrogen bond. In the crystal, weak C-H?O inter-actions link the mol-ecules
      into zigzag chains along [010].

PMID- 22606123
TI  - 3,5-Bis(adamantan-1-yl)-1-meth-oxy-benzene.
AB  - In title compound, C(27)H(36)O, all cyclo-hexane rings within the adamantyl
      groups adopt chair conformations. There are no obvious inter-molecular hydrogen
      bonds in the structure, so that van der Waals attractions stabilize the crystal.

PMID- 22606124
TI  - (E)-4-(4-Meth-oxy-phen-yl)but-3-en-2-one.
AB  - In the title compound, C(11)H(12)O(2), the dihedral angle between the benzene
      ring and the but-3-en-2-one group is 4.04 (5) degrees . The crystal packing
      features chains, parallel to [-101], composed of dimers connected by weak C-H?O
      inter-actions..

PMID- 22606125
TI  - (E)-4-[(1-Benzyl-4-benzyl-idene-2,5-di-oxopyrrolidin-3-yl)meth-yl]benzalde-hyde
      0.25-hydrate.
AB  - The crystal structure of the title compound, C(26)H(21)NO(3).0.25H(2)O, reveals
      one stereogenic centre in the mol-ecule. Nevertheless, due to the observed
      centrosymmetric space group, both enanti-omers are present in the crystal
      packing. The water molecule of crystallisation is located on a crystallographic
      inversion center. The mol-ecule contains one five-membered ring (A) and three six
      membered rings (benzyl ring B, benzyl-idene ring C and formyl-benzyl ring D). All
      four rings are not coplanar: the dihedral angles between rings A and B, A and C,
      and A and D are 70.35 (9), 33.8 (1) and 60.30 (9) degrees , respectively. In the
      crystal, pairs of weak C-H?O inter-actions lead to the formation of
      centrosymmetric dimers. Additional C-H?O inter-actions link the dimers into
      chains along [011].

PMID- 22606126
TI  - 4-Bromo-benzoic acid-6-(4-bromo-phen-yl)-3-methyl-1,2,4-triazolo[3,4
      b][1,3,4]thia-diazole (1/1).
AB  - In the title 1:1 co-crystal, C(10)H(7)BrN(4)S.C(7)H(5)BrO(2), the triazolothia
      diazole system is approximately planar [with a maximum deviation of 0.030 (4) A]
      and forms a dihedral angle of 8.6 (1) degrees  with the bromo-phenyl ring. In the
      carb-oxy-lic acid mol-ecule, the carboxyl group is rotated by 6.4 (3) degrees 
      out of the benzene ring plane. The crystal structure features O-H?N and C-H?O
      hydrogen bonds, pi-pi stacking inter-actions [centroid-centroid distances = 3.713
      (2), 3.670 (2) and 3.859 (3) A] and short S?N [2.883 (4) A] contacts.

PMID- 22606127
TI  - 1-(2,4,6-Trioxo-1,3-diazinan-5-yl-idene)thio-semicarbazide.
AB  - The title mol-ecule, C(5)H(5)N(5)O(3)S, is approximately planar, with a maximum
      deviation from the mean plane through the non-H atoms of 0.182 (3) A for the
      amine N atom. In the crystal, mol-ecules are connected via N-H?O and N-H?S inter
      actions, building a three-dimensional hydrogen-bonded network. Additionally, a
      weak intra-molecular N-H?O hydrogen bond is observed.

PMID- 22606128
TI  - 1,3-Bis(1-phenyl-eth-yl)imidazolidine-2-thione.
AB  - The complete molecule of the title compound, C(19)H(22)N(2)S, is generated by
      crystallographic twofold symmetry with the C=S group lying on the rotation axis.
      The imidazolidine ring adopts a flattened twist conformation. The dihedral angle
      between the asymmetric part of the imidazolidine-2-thione fragment and the
      benzene ring is 89.49 (17) degrees .

PMID- 22606129
TI  - 3-Acetyl-1-(3-chloro-phen-yl)thio-urea.
AB  - In the title compound, C(9)H(9)ClN(2)OS, the 3-chloro-phenyl and acetyl-thio-urea
      fragments are oriented at a dihedral angle of 62.68 (5) degrees . An intra
      molecular N-H?O hydrogen bond generates an S(6) ring motif. Mol-ecules are linked
      into dimers via a cyclic R(2) (2)(8) motif of N-H?S hydrogen bonds. These dimers
      are further connected through C-H?S inter-actions, completing an R(2) (2)(12)
      motif, into chains along [010].

PMID- 22606130
TI  - 2-[(3,5-Diphenyl-1H-pyrazol-1-yl)meth-yl]pyridine.
AB  - The title compound, C(21)H(17)N(3), crystallizes with the phenyl ring in the 3
      position coplanar with the pyrazole ring within 4.04 (5) degrees , whereas the
      phenyl ring in the 5-position forms a dihedral angle of 50.22 (3) degrees  with
      the pyrazole ring. There is no ambiguity regarding the position of pyridine N
      atom, which could have exhibited disorder between the ortho positions of the
      ring.

PMID- 22606131
TI  - 4-Methyl-2-oxo-2H-chromen-7-yl 4-methyl-benzene-sulfonate.
AB  - In the title compound, C(17)H(14)O(5)S, the coumarin ring system is nearly
      planar, with a maximum deviation of 0.034 (2) A from the mean plane. The dihedral
      angle between the benzene ring and the coumarin ring system is 56.11 (6) degrees
      . The crystal packing is stabilized by C-H?O hydrogen bonding, which forms a
      three-dimensional framework.

PMID- 22606132
TI  - 1,1':4',1''-Terphenyl-2',5'-dicarb-oxy-lic acid dimethyl sulfoxide-d(6)
      disolvate.
AB  - The asymmetric unit of the title solvate, C(20)H(14)O(4).2C(2)D(6)OS, contains
      half of the substituted terephthalic acid mol-ecule and one solvent mol-ecule.
      The centroid of the central benzene ring in the acid mol-ecule is coincident with
      a crystallographic inversion center. Neither the carboxyl nor the phenyl
      substituents are coplanar with the central aromatic ring, showing dihedral angles
      of 53.18 (11) and 47.83 (11) degrees , respectively. The dimethyl sulfoxide
      solvent mol-ecules are hydrogen bonded to the carb-oxy-lic acid groups.

PMID- 22606133
TI  - 2-Methyl-1-(4-methyl-phenyl-sulfon-yl)naphtho-[2,1-b]furan.
AB  - In the title compound, C(20)H(16)O(3)S, the 4-methyl-phenyl ring makes a dihedral
      angle of 83.07 (3) degrees  with the mean plane [r.m.s. deviation = 0.020 (1) A]
      of the naphtho-furan fragment. In the crystal, mol-ecules are linked by weak C
      H?O and C-H?pi inter-actions.

PMID- 22606134
TI  - 5-Methyl-spiro-[indoline-3,7'-[6H,7H,8H]pyrano[3,2-c:5,6-c']di[1]benzopyran]
      2,6',8'-trione chloroform hemisolvate.
AB  - In the title compound, C(27)H(15)NO(6).0.5CHCl(3), the central pyran ring and
      both the benzopyran systems are planar, with the dihedral angle between the outer
      rings being 3.24 (6) degrees . The indolin-2-one system is in a perpendicular
      configuration with respect to the pyran ring [dihedral angle = 87.58 (2) degrees
      ]. Supra-molecular layers in the ac plane are formed in the crystal structure
      whereby inversion-related mol-ecules are connected by N-H?O hydrogen bonds. These
      are further linked by C-H?O inter-actions, forming a supra-molecular layer in the
      ac plane. Disordered CHCl(3) solvent in the structure was modelled with the
      SQUEEZE routine in PLATON [Spek (2009 ?). Acta Cryst. D65, 148-155].

PMID- 22606135
TI  - 4beta-Hy-droxy-12,13-ep-oxy-trichothec-9-ene.
AB  - The asymmetric unit in the crystal of the title compound, C(15)H(22)O(3),
      contains two independent mol-ecules with similar structures. Each mol-ecule
      contains two six-membered rings and one five-membered ring. The five-membered
      ring displays an envelope conformation with the C atom linking the epoxy group as
      the flap, while the two six-membered rings show half-chair conformations. The two
      independent mol-ecules are linked by an O-H?O hydrogen bond. These dimers are
      further linked by O-H?O hydrogen bonds, forming supra-molecular chains running
      along the a axis.

PMID- 22606136
TI  - 4-{2-[(E)-Cyclo-pentyl-idene]hydrazin-1-yl}benzene-sulfonamide.
AB  - The title mol-ecule, C(11)H(15)N(3)O(2)S, features a five-membered ring which is
      twisted about the middle CH(2)-CH(2) bond. The benzene ring is inclined with
      respect to the imine residue [C-N-N-C torsion angle = 165.4 (2) degrees ]. Supra
      molecular layers in the bc plane are formed by hydrogen bonds between the amine H
      atoms and sulfonamide O and imine N atoms, as well as by a weak hydrazine H-atom
      inter-molecular inter-action with the second sulfonamide O atom.

PMID- 22606137
TI  - (Z)-1-(2,4-Difluoro-phen-yl)-3-(4-fluoro-phen-yl)-2-(1H-1,2,4-triazol-1-yl)prop-2
      en-1-one.
AB  - In the title mol-ecule, C(17)H(10)F(3)N(3)O, the C=C bond connecting the triazole
      ring and 4-fluoro-phenyl groups adopts a Z conformation. The triazole ring forms
      dihedral angles of 15.3 (1) and 63.5 (1) degrees , with the 2,4-difluoro
      substituted and 4-fluoro-substituted benzene rings, respectively. The dihedral
      angle between the two benzene rings is 51.8 (1) degrees .

PMID- 22606138
TI  - 5-Amino-1,3,4-thia-diazol-2(3H)-one.
AB  - The asymmetric unit of the title compound, C(2)H(3)N(3)OS, contains three
      independent mol-ecules which are essentially planar, with r.m.s. deviations of
      0.011 (2)-0.027 (2) A from the mean plane defined by the seven non-H atoms. In
      the crystal, N-H?N and N-H?O hydrogen bonds link the mol-ecules into a sheet
      parallel to the (111) plane.

PMID- 22606139
TI  - Polymorph of 4-(carbazol-9-yl)benzo-nitrile.
AB  - The asymmetric unit of the title compound, C(19)H(12)N(2), contains two
      independent mol-ecules with a similar structure. In the two mol-ecules, the
      dihedral angles between the carbazole ring system and the benzene ring are 47.9
      (5) and 45.4 (4) degrees , similar to the value of 47.89 (6) degrees  found in
      the previously reported structure [Saha & Samanta (1999 ?). Acta Cryst. C55, 1299
      1300]. In the crystal, there is a weak C-H?N hydrogen bond between the two
      independent mol-ecules.

PMID- 22606140
TI  - (3,5-Dimethyl-phen-yl)[8-(3,5-dimethyl-benzo-yl)-2,7-dimeth-oxy-naphthalen-1
      yl]methanone.
AB  - In the title mol-ecule, C(30)H(28)O(4), the inter-planar angle between the two
      benzene rings of the 3,5-dimethyl-benzoyl groups is 50.35 (7) degrees . The
      dihedral angles between the two benzene rings and the naphthalene ring system are
      81.87 (6) and 83.55 (6) degrees . In addition, the conformations of the pairs of
      methyl groups and their counterparts differ from each other though their
      environment is very similar. In the crystal, weak C-H?O inter-actions occur.

PMID- 22606141
TI  - 4,4'-Bipyridine-trans,trans-hexa-2,4-dienedioic acid (1/1).
AB  - The title cocrystal, C(10)H(8)N(2).C(6)H(6)O(4), crystallizes with half-mol
      ecules of 4,4'-bipyridine and trans,trans-hexa-2,4-dienedioic acid in the
      asymmetric unit, as each is located about a crystallographic inversion center.
      The bipyridine molecule is planar from symmetry. In the dicarboxylic acid
      molecule, the O-C-C-C torsion angle is -13.0 (2) degrees . In the crystal, O-H?N
      and C-H?O hydrogen bonds generate a three-dimensional network.

PMID- 22606142
TI  - 4-(Dimeth-oxy-meth-yl)phenyl 2,3,4,6-tetra-O-acetyl-beta-d-glucopyran-oside.
AB  - The enanti-omerically pure title compound, C(23)H(30)O(12), crystallizes in the
      chiral space group P2(1)2(1)2(1). The O-acetyl-ated-glucopyran-oside moiety
      adopts a chair conformation. Numerous C-H?O inter-actions as well as a C-H?pi
      inter-action are present in the crystal structure.

PMID- 22606143
TI  - 2-[1-(1-Phenyl-eth-yl)imidazolidin-2-yl-idene]malononitrile.
AB  - In the title compound, C(14)H(14)N(4), the imidazolidine moiety is nearly planar,
      having an N-C-N-C torsion angle of 4.43 (3) degrees . The crystal structure is
      characterized by classical N-H?N hydrogen bonds, which form inversion dimers.

PMID- 22606144
TI  - Cyclo-octanaminium hydrogen succinate monohydrate.
AB  - In the title hydrated salt, C(8)H(18)N(+).C(4)H(5)O(4) (-).H(2)O, the cyclo-octyl
      ring of the cation is disordered over two positions in a 0.833 (3):0.167 (3)
      ratio. The structure contains various O-H..O and N-H?O inter-actions, forming a
      hydrogen-bonded layer of mol-ecules perpendicular to the c axis. In each layer,
      the ammonium cation hydrogen bonds to two hydrogen succinate anions and one water
      mol-ecule. Each hydrogen succinate anion hydrogen bonds to neighbouring anions,
      forming a chain of mol-ecules along the b axis. In addition, each hydrogen
      succinate anion hydrogen bonds to two water mol-ecules and the ammonium cation.

PMID- 22606145
TI  - N'-Cyclo-dodecyl-idene-pyridine-4-carbohydrazide.
AB  - The title compound, C(18)H(27)N(3)O, is a derivative of the anti-tuberculosis
      drug isoniazid (systematic name: pyridine-4-carbohydrazidei). The crystal
      structure consists of repeating C(4) chains along the b axis, formed by N-H?O
      hydrogen bonds with adjacent amide functional groups that are related by a b
      glide plane. The cyclo-dodecyl ring has the same approximately 'square'
      conformation, as seen in the parent hydro-carbon cyclo-dodecane.

PMID- 22606146
TI  - 41-Azido-41-de-oxy-rapamycin.
AB  - The title compound, C(51)H(78)N(4)O(12), is a derivative of rapamycin, a triene
      macrolide anti-biotic mol-ecule isolated from Streptomyces hygroscopicus. The
      macrocyclic ring structure has 15 chiral centres, with one of the substituent hy
      droxy groups giving an intra-molecular hydrogen bond to a ketone O-atom acceptor.
      The mol-ecules also form inter-molecular hy-droxy-ketone O-H?O hydrogen-bonding
      associations, giving one-dimensional chains extending along (010). The crystal
      has 108 A(3) solvent-accessible voids.

PMID- 22606147
TI  - 5alpha-Hy-droxy-eudesm-4(15),11(13)-dien-8beta,12-olide.
AB  - The title compound, C(15)H(20)O(3), a sesquiterpene lactone, was isolated from
      the aerial parts of Carpesium minus Hemsl. (Compositae). The mol-ecule is
      composed of three rings, with the two cyclo-hexane rings in chair conformations
      and the cyclo-pentane ring adopting a twist conformation. The A/B ring junction
      is trans-fused. The absolute configuration shown has been arbitrarily assigned.
      In the crystal, mol-ecules are linked into [100] chains by O-H?O hydrogen bonds.

PMID- 22606148
TI  - 4-Chloro-N'-(3,5-dibromo-2-hy-droxy-benzyl-idene)benzohydrazide.
AB  - The asymmetric unit of the title compound, C(14)H(9)Br(2)ClN(2)O(2), contains two
      independent mol-ecules. Both mol-ecules adopt an E configuration about the C=N
      bond. The dihedral angles between the benzene rings are 30.0 (2) and 51.6 (2)
      degrees  in the two mol-ecules. In the crystal, mol-ecules are linked through N
      H?O hydrogen bonds, forming chains along the b axis. In addition, there is an
      intra-molecular O-H?N hydrogen bond in each mol-ecule.

PMID- 22606149
TI  - 4-(Anthracen-9-yl)-2-phenyl-6-(pyridin-2-yl)pyridine.
AB  - In the title compound, C(30)H(20)N(2), the anthracene ring system is
      approximately planar [maximum deviation = 0.035 (2) A] and is nearly
      perpendicular to the central pyridine ring, making a dihedral angle of 75.73 (7)
      degrees . The terminal pyridine ring and the phenyl ring are oriented at dihedral
      angles of 8.11 (10) and 13.22 (10) degrees , respectively, to the central
      pyridine ring.

PMID- 22606150
TI  - 3beta-Chloro-5alpha-cholestan-6-one.
AB  - The asymmetric unit of the title compound, C(27)H(45)ClO, consists of two
      crystallographically independent mol-ecules. In both mol-ecules, the three cyclo
      hexane rings in the steroid fused-ring systems adopt chair conformations, while
      the cyclo-pentane ring adopts a half-chair conformation in one mol-ecule and an
      envelope conformation in the other. In the crystal, the mol-ecules are linked
      into a two-dimensional network by weak C-H?O hydrogen bonds. The crystal studied
      is a nonmerohedral twin with a refined ratio of twin components of 0.264
      (3):0.736 (3).

PMID- 22606151
TI  - Ethyl 7-methyl-3-oxo-5-phenyl-2-(2,4,6-trimeth-oxy-benzyl-idene)-2,3-dihydro-5H
      thia-zolo[3,2-a]pyrimidine-6-carboxyl-ate.
AB  - In the title compound, C(26)H(26)N(2)O(6)S, the benzene ring is positioned
      axially to the thia-zolopyrimidine ring and bis-ects it with a dihedral angle of
      80.94 (7) degrees . The pyrimidine ring adopts a flattened boat conformation. In
      the crystal, pairs of bifurcated C-H?O hydrogen bonds link the mol-ecules into
      chains along the c axis.

PMID- 22606152
TI  - 7-Chloro-4-[(E)-2-(3,4,5-trimeth-oxy-benzyl-idene)hydrazin-1-yl]quinoline.
AB  - In the title compound, C(19)H(18)ClN(3)O(3), the r.m.s. deviation through the 23
      non-H and non-meth-oxy atoms is 0.088 A, indicating a planar mol-ecule with the
      exception of the meth-oxy groups. One meth-oxy group, surrounded on either side
      by the other meth-oxy groups, is almost normal to the benzene ring to which it is
      connected [C-O-C(ar)-C(ar) torsion angle = 81.64 (15) degrees ]. In the crystal,
      N-H?O, C-H?O and pi-pi inter-actions [between quinoline residues; centroid
      centroid distance = 3.4375 (8) A] link mol-ecules into a three-dimensional
      architecture.

PMID- 22606153
TI  - Benzyl 2-methyl-3-[(E)-(thio-phen-2-yl)methyl-idene]dithio-carbazate.
AB  - In the title compound, C(14)H(14)N(2)S(3), the thione S atom and methyl group are
      syn, as are the two thio-ether S atoms. The mol-ecule is twisted, the dihedral
      angles between the central (C(2)N(2)S(2)) residue and the pendent 2-thienyl and
      phenyl rings being 21.57 (6) and 77.54 (3) degrees , respectively. In the
      crystal, mol-ecules assemble into a three-dimensional architecture via C-H?pi
      inter-actions, involving both the five- and six-membered rings as acceptors, as
      well as S?S inter-actions [3.3406 (5) A] between centrosymmetrically related 2
      thienyl rings.

PMID- 22606154
TI  - 3,4-Dimethyl-pyrano[2,3-c]pyrazol-6(2H)-one.
AB  - The asymmetric unit of the title compound, C(8)H(8)N(2)O(2), comprises two
      independent mol-ecules in both of which, all non-H atoms lie in a common plane
      (r.m.s. deviation = 0.014 and 0.017 A). In the crystal, N-H?O hydrogen bonds
      connect the mol-ecules into zigzag chains running along [10-1]. Weak C-H?O inter
      actions connect the chains into an infinite network.

PMID- 22606155
TI  - 2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl 2-bromo-benzoate.
AB  - In the title compound, C(13)H(12)BrN(3)O(4), the dihedral angle between the
      benzene and imidazole rings is 30.6 (2) degrees . In the crystal, mol-ecules are
      linked into chains parallel to [001] by C-H?O hydrogen bonds. The crystal packing
      is further consolidated by pi-pi inter-actions [centroid-centroid distance =
      3.482 (2) A].

PMID- 22606156
TI  - 1-(4-Chloro-phen-yl)-3-(morpholin-4-yl)urea.
AB  - In the title mol-ecule, C(11)H(14)ClN(3)O(2), the morpholine ring has a chair
      conformation. In the crystal, pairs of mol-ecules are linked into inversion
      dimers by N-H?O hydrogen bonds.

PMID- 22606157
TI  - N-Cyclo-hexyl-pyrrolidine-1-carbothio-amide.
AB  - In the title mol-ecule, C(11)H(20)N(2)S, the five-membered ring has an envelope
      conformation and the cyclo-hexane ring is in a chair conformation. The N-H group
      is not involved in any intra- or inter-molecular inter-actions.

PMID- 22606158
TI  - 4-Nitro-2-{[(tricyclo-[3.3.1.1(3,7)]decan-1-yl)iminium-yl]meth-yl}phenolate.
AB  - The title compound, C(17)H(20)N(2)O(3), is a Schiff base, which is found as a
      zwitterion in the solid state. The geometry around the iminium N atom indicates
      sp(2)-hybridization. The zwitterion shows a strong intra-molecular N-H?O hydrogen
      bond inter-action between the iminium N atom and the phenolate O atom.

PMID- 22606159
TI  - 2-(4-Isobutyl-phen-yl)-N'-[(3Z)-2-oxoindolin-3-yl-idene]propano-hydrazide.
AB  - In the title compound, C(21)H(23)N(3)O(2), the indolin-2-one group is essentially
      planar, with a maximum deviation of 0.016 (2) A for the N atom, and makes a
      dihedral angle of 84.38 (14) degrees  with the benzene ring. The =N-N(H)-C(=O)-C-
      torsion angle is 0.9 (3) degrees . In the crystal, mol-ecules are linked into a
      three-dimensional network via N-H?O and C-H?O hydrogen bonds. In addition, a C
      H?pi inter-action was observed.

PMID- 22606160
TI  - Methyl 4',5-dichloro-2-hy-droxy-4,6-dimethyl-biphenyl-3-carboxyl-ate.
AB  - In the title compound, C(16)H(14)Cl(2)O(3), the dihedral angle between the mean
      planes of the two benzene rings is 55.30 (5) degrees . The methyl ester group
      lies within the ring plane due to an intra-molecular O-H?O hydrogen bond [maximum
      deviation from the C(8)O(2) mean plane is 0.0383 (13) A]. In the crystal, mol
      ecules are held together by rather weak C-H?O hydrogen bonds.

PMID- 22606161
TI  - 4,4-Dimethyl-2-[3-nitro-2-phenyl-1-(phenyl-sulfan-yl)prop-yl]-4,5-dihydro-1,3
      oxazole.
AB  - In the title compound, C(20)H(22)N(2)O(3)S, the oxazoline ring is planar (r.m.s.
      deviation = 0.045 A) and forms dihedral angles of 47.24 (8) and 10.11 (8) degrees
      with the S- and C-bound phenyl rings, respectively. The nitro group lies to the
      same side of the mol-ecule as the oxazoline ring but is orientated so as not to
      inter-act with the ring. Linear supra-molecular chains along [010] are formed via
      C-H?O and C-H?S contacts. Chains are consolidated into a three-dimensional
      architecture by C-H?pi and van der Waals inter-actions.

PMID- 22606162
TI  - 1,4-Phenyl-enebis(methyl-ene) dicarbamate.
AB  - The title compound, C(10)H(12)N(2)O(4), is a phenyl dicarbamate with
      crystallographically imposed inversion symmetry. The dihedral angle between the
      carbamo-yloxy plane [i.e. the plane of the N-C(O)-O fragment; r.m.s. deviation =
      0.002 (3) A] and the plane of the aryl ring is 29.2 (1) degrees . In the crystal,
      two different centrosymmetric N-H?O hydrogen-bond inter-actions are observed;
      these are described as R(2) (2)(8) and R(2) (4)(8) in graph-set notation. The
      rings form an alternating sequence, linking the mol-ecules into a sheet structure
      parallel to (011).

PMID- 22606163
TI  - 1-(5-Benzyl-sulfanyl-2,2-dimethyl-2,3-dihydro-1,3,4-thia-diazol-3-yl)-2,2
      dimethyl-propan-1-one.
AB  - In the title compound, C(16)H(22)N(2)OS(2), the S atom of the thia-diazole ring
      and the attached methyl groups are disordered over two orientations with a
      refined site-occupancy ratio of 0.641 (11):0.359 (11). The thia-diazole ring is
      in a twist conformation in both disorder components. The mean plane through the
      thia-diazole ring makes dihedral angles of 77.39 (8) (major component) and 67.45
      (11) degrees  (minor component) with the benzene ring. Intra-molecular C-H?N
      inter-actions generate two S(6) ring motifs. In the crystal, mol-ecules are
      linked by C-H?O hydrogen bonds into zigzag chains parallel to the b axis.

PMID- 22606164
TI  - (3beta,18beta,20beta)-N-Eth-oxy-carbonyl-methyl-3-nitrato-11-oxoolean-12-ene-29
      carboxamide methanol monosolvate.
AB  - The title compound, C(34)H(52)N(2)O(7).CH(4)O, is the methanol solvate of a
      difunctionalized derivative of the therapeutic agent 18beta-glycyrrhetinic acid,
      a penta-cyclic triterpene. The five six-membered rings of the glycyrrhetinic acid
      moiety show normal geometries, with four rings in chair conformations and the
      unsaturated ring in a half-chair conformation. This moiety is substituted by a
      nitrate ester group and an O-ethyl-glycine group. In the crystal, the nonsolvent
      mol-ecules are packed parallel to (010) in a herringbone fashion with the
      nitrato, ethyl-glycine and methanol-O atom being proximate. The methanol solvent
      mol-ecule is anchored via a donated O-H?O(ac-yl) and an accepted N-H?O hydrogen
      bond, giving rise to infinite zigzag chains of hydrogen bonds parallel to [100].
      Two weak intermolecular C-H?O interactions to the methanol and to an acyl oxygen
      establish links along [100] and [010], respectively.

PMID- 22606165
TI  - Oosporein from Tremella fuciformis.
AB  - THE TITLE COMPOUND [SYSTEMATIC NAME: 3,3',6,6'-tetra-hydroxy-4,4'-dimethyl-1,1'
      bi(cyclo-hexa-3,6-diene)-2,2',5,5'-tetra-one], C(14)H(10)O(8), was isolated from
      Tremella fuciformis. The mol-ecule has 2 symmetry, with the mid-point of the C-C
      bond linking the cyclo-hexa-dienedione rings located on a twofold rotation axis.
      In the mol-ecule, the ring is approximately planar, with an r.m.s. deviation of
      0.0093 A, and the two rings make a dihedral angle of 67.89 (5) degrees . Inter
      molecular O-H?O hydrogen bonding occurs in the crystal structure.

PMID- 22606166
TI  - 4-[(E)-2-(2,4-Dichloro-benzyl-idene)hydrazin-1-yl]quinolin-1-ium chloride
      monohydrate.
AB  - In the title hydrated salt, C(16)H(12)Cl(2)N(3) (+).Cl(-).H(2)O, there is a small
      twist in the cation as seen in the torsion angle linking the benzene ring to the
      rest of the mol-ecule [171.96 (17) degrees ]. In the crystal, the quinolinium H
      atom forms a hydrogen bond to the lattice water mol-ecule, which also forms
      hydrogen bonds to two Cl(-) anions. Each Cl(-) ion also accepts a hydrogen bond
      from the hydrazine H atom. The three-dimensional architecture is also stabilized
      by pi-pi inter-actions between centrosymmetrically related quinoline residues
      [centroid-centroid distance = 3.5574 (11) A].

PMID- 22606167
TI  - 4-Bromo-N-(4-meth-oxy-2-nitro-phen-yl)benzamide.
AB  - In the title compound, C(14)H(11)BrN(2)O(4), the amide segment makes dihedral
      angles of 23.4 (2) and 20.5 (2) degrees  with the benzene rings, while the
      dihedral angle between the bezene rings is 2.90 (8) degrees . The nitro and meth
      oxy groups are almost coplanar with their bound benzene ring, with the r.m.s.
      deviation for the 11 non-H atoms being 0.0265 (1) A. An intra-molecular N-H?O
      hydrogen bond generates an S(6) ring motif. In the crystal, mol-ecules are linked
      into [2-10] chains by weak C-H?O and C-H?Br inter-actions, which form an R(2)
      (2)(8) motif between pairs of mol-ecules in the chain. A Br?O [3.2018 (12) A]
      short contact also occurs.

PMID- 22606168
TI  - 4-(4-Nitro-phen-yl)morpholine.
AB  - Aromatic pi-pi stacking inter-actions stabilize the crystal structure of the
      title compound, C(10)H(12)N(2)O(3), the perpendic-ular distance between parallel
      planes being 3.7721 (8) A. The morpholine ring adopts a chair comformation.

PMID- 22606169
TI  - 4-[(2'-Cyano-biphenyl-4-yl)meth-yl]morpholin-4-ium perchlorate.
AB  - In the title salt, C(18)H(19)N(2)O(+).ClO(4) (-), the morpholinium ring adopts a
      chair conformation, while the two benzene rings make a dihedral angle of 62.65
      (17) degrees . Inter-molecular N-H?N hydrogen bonds and weak C-H?O inter-actions
      occur in the crystal structure.

PMID- 22606170
TI  - 2-(4-Fluoro-phen-yl)-5-iodo-3-phenyl-sulfinyl-1-benzofuran.
AB  - In the title compound, C(20)H(12)FIO(2)S, the dihedral angles between the mean
      plane [r.m.s. deviation = 0.014 (1) A] of the benzofuran fragment and the pendant
      4-fluoro-phenyl and phenyl rings are 8.0 (1) and 86.06 (6) degrees ,
      respectively. In the crystal, mol-ecules are linked by weak C-H?O hydrogen bonds.
      The crystal structure also exhibits weak pi-pi inter-actions between the furan
      and benzene rings of neighbouring mol-ecules [centroid-centroid distance = 3.547
      (2) A, inter-planar distance = 3.397 (2) A and slippage = 1.021 (2) A].

PMID- 22606171
TI  - 1-Fluoro-3,3-dimethyl-1,3-dihydro-1lambda(3)-benzo[d][1,2]iodoxole.
AB  - The asymmetric unit of the title compound, C(9)H(10)FIO, contains two independent
      mol-ecules which are weakly bound by inter-molecular O?I inter-actions [3.046 (4)
      and 2.947 (4) A]. The two covalent I-F bonds are slightly longer than the two I-O
      bonds.

PMID- 22606172
TI  - 2,11-Dibromo-5,8-dibut-yl[4]helicene.
AB  - A racemic mixture of the title compound, C(26)H(26)Br(2), a brominated
      [4]helicene, crystallizes, forming columns of stacked mol-ecules. There are two
      crystallographically unique mol-ecules in the asymmetric unit, both with the same
      helical handedness. As is typical with helicene congeners, the unique mol-ecules
      show short inter-atomic contacts between H atoms at the fjord region, with H?H
      distances of 1.87 and 1.94 A. Mol-ecules with the same helical handedness
      segregate in the crystal packing, forming homochiral columns. The stacked mol
      ecules are piled in a column with alternate orientations. The shortest C?C
      distance in the stacked mol-ecules is 3.306 (4) A.

PMID- 22606173
TI  - 5-Nitro-1-(prop-2-yn-1-yl)-2,3-dihydro-1H-1,3-benzodiazol-2-one.
AB  - In the two independent mol-ecules of the title compound, C(10)H(7)N(3)O(3), the
      nitro substitutent is twisted slightly with respect to the benzodiazol fused-ring
      system [dihedral angles = 4.9 (3) and 8.5 (1) degrees ]. The two independent mol
      ecules are disposed about a pseudo inversion center and are held together by N
      H?O hydrogen bonds. The supramolecular dimer is essentially planar [dihedral
      angle between the fused rings = 2.0 (1) degrees ]. Adjacent dimers are linked by
      acetyl-ene-nitro C-H?O inter-actions, generating a ribbon motif along (110).

PMID- 22606174
TI  - 5-({3-[(5-Amino-1,3,4-thia-diazol-2-yl)sulfanylmeth-yl]benz-yl}sulfan-yl)-1,3,4
      thia-diazol-2-amine.
AB  - In the title compound, C(12)H(12)N(6)S(4), the two terminal thia-diazole rings
      are twisted with respect to the central benzene ring, making dihedral angles of
      54.28 (4) and 76.56 (3) degrees . The dihedral angle between the two thia-diazole
      rings is 27.77 (4) degrees . Inter-molecular N-H?N hydrogen bonds stabilize the
      crystal packing, linking the mol-ecules into a tape along the b axis.

PMID- 22606175
TI  - 3,6-Diiodo-9H-carbazole.
AB  - In the title compound, C(12)H(7)I(2)N, the tricyclic aromatic ring system is
      essentially planar, with an r.m.s. deviation of 0.0272 A. The two I atoms are
      marginally out of plane, with the C-I bonds angled at 3.9 (2) and 1.1 (2) degrees
      with respect to the planes of their respective benzene rings, above and below
      the plane of the carbazole ring system. No classical hydrogen bonds are observed
      in the crystal structure.

PMID- 22606176
TI  - 4,4'-[(5-Carb-oxy-1,3-phenyl-ene)bis-(-oxy)]dibenzoic acid.
AB  - In the title compound, C(21)H(14)O(8), the central benzene ring makes dihedral
      angles of 77.8 (6) and 75.9 (5) degrees  with the outer benzene rings. In the
      crystal, mol-ecules are linked by O-H?O hydrogen bonds involving carboxyl groups,
      forming one-dimensional ladders. Two-dimensional layers are formed by inter
      penetration of these one-dimensional ladders.

PMID- 22606177
TI  - 7-Chloro-4-[(E)-2-(2,5-dimeth-oxy-benzyl-idene)hydrazin-1-yl]quinoline.
AB  - In the nearly planar title compound (r.m.s. deviation for the 24 non-H atoms =
      0.064 A), C(18)H(16)ClN(3)O(2), the conformation about the N=C bond is E. Supra
      molecular chains propagated by glide symmetry along [001] are found in the
      crystal packing. These are sustained by N-H?N hydrogen bonds with the quinoline N
      atom being the acceptor. The chains are connected into a three-dimensional
      architecture by pi-pi inter-actions involving all three aromatic rings [centroid
      centroid distances = 3.5650 (9)-3.6264 (9) A].

PMID- 22606178
TI  - 1-(4-Bromo-phenyl-sulfin-yl)-2-methyl-naphtho-[2,1-b]furan.
AB  - In the title compound, C(19)H(13)BrO(2)S, the 4-bromo-phenyl ring makes a
      dihedral angle of 83.75 (4) degrees  with the mean plane of the naphtho-furan
      fragment [r.m.s. deviation = 0.024 (2) A]. In the crystal, mol-ecules are linked
      via pairs of C-H?O hydrogen bonds, forming inversion dimers. These dimers are
      connected by weak pi-pi inter-actions between the central naphtho-furan benzene
      rings of neighbouring mol-ecules [centroid-centroid distance = 3.483 (2) A, inter
      planar distance = 3.416 (2) A and slippage = 0.680 (2) A].

PMID- 22606179
TI  - (2-Bromo-phen-yl)(4-hy-droxy-1,1-dioxo-2H-1,2-benzothia-zin-3-yl)methanone.
AB  - In the title mol-ecule, C(15)H(10)BrNO(4)S, the heterocyclic thia-zine ring
      adopts a half-chair conformation, with the S and N atoms displaced by 0.554 (7)
      and 0.198 (8) A, respectively, on opposite sides of the mean plane formed by the
      remaining ring atoms. The mol-ecular structure is consolidated by intra-molecular
      O-H?O inter-actions and the crystal packing features N-H?O and C-H?O hydrogen
      bonds.

PMID- 22606180
TI  - 1-(1,3-Benzothia-zol-2-yl)-3-phenyl-2-pyrazoline.
AB  - In the title compound, C(16)H(13)N(3)S, the pyrazoline ring forms dihedral angles
      of 6.89 (14) and 4.96 (11) degrees  with the benzene ring and the benzothia-zole
      group, respectively. In the crystal, weak C-H?N inter-actions link the mol-ecules
      into chains extending along the b-axis direction.

PMID- 22606181
TI  - 2,7-Bis(2-nitro-phen-yl)-9-octyl-9H-carbazole.
AB  - The title compound, C(32)H(31)N(3)O(4), was obtained in a Suzuki coupling of
      carbazole diboronic acid and bromo-nitro-benzene. In the crystal, the mol-ecule
      adopts a non-symmetric conformation. The carbazole ring system is approximately
      planar [maximum deviation from the least-squares plane = 0.039 (2) A]. The planes
      of the carbazole unit and the benzene rings subtend dihedral angles of 48.42 (7)
      and 41.81 (6) degrees . The dihedral angles between the planes of the nitro
      phenyl rings and the nitro groups are 44.34 (19) and 61.64 (15) degrees . The
      crystal is built from two strands of parallel mol-ecules with inter-digitated
      octyl chains. These strands are symmetry related by a twofold screw axis.

PMID- 22606182
TI  - 2-Cyano-2-methyl-propanamide.
AB  - In the crystal structure of the title compound, C(5)H(8)N(2)O, mol-ecules are
      linked via pairs of N-H?O hydrogen bonds, forming inversion dimers. These dimers
      are linked via pairs of N-H?H hydrogen bonds into zigzag chains propagating along
      [101].

PMID- 22606183
TI  - 2-Hy-droxy-N'-[2-(6-meth-oxy-naphthalen-2-yl)propano-yl]benzohydrazide.
AB  - In the title compound, C(21)H(20)N(2)O(4), the naphthalene ring system makes a
      dihedral angle of 84.5 (3) degrees  with the benzene ring, and the -C(=O)-N(H)
      N(H)-C(=O)- torsion angle is 70.7 (7) degrees , so that the mol-ecule is twisted.
      An S(6) ring motif is formed via an intra-molecular O-H?O hydrogen bond. In the
      crystal, mol-ecules are linked by N-H?O and C-H?O hydrogen bonds into supra
      molecular layers in the ab plane.

PMID- 22606184
TI  - (2S,4S)-2-[(S,E)-2-Bromo-1-nitro-methyl-3-phenyl-all-yl]-4-methyl-cyclo-hexa
      none.
AB  - The crystal structure of the title compoud, C(17)H(20)BrNO(3), contains three
      chiral centers, which all exhibit an S configuration. The C=C double bond has an
      E conformation. The cyclo-hexane ring is in a chair conformation. In the crystal,
      mol-ecules are linked by weak N-O?Br inter-actions [O?Br = 3.136 (4) A].

PMID- 22606185
TI  - 2-Chloro-benzohydrazide.
AB  - The asymmetric unit of the the title compound, C(7)H(7)ClN(2)O, contains two mol
      ecules in which the chloro-phenyl and the formic hydrazide units are almost
      planar (r.m.s. deviations of 0.0081 and 0.0100 A, respectively, in one mol-ecule
      and 0.0069 and 0.0150 A in the other) and are oriented with respect to each other
      at dihedral angles of 56.8 (2) and 56.9 (2) degrees . In the crystal, the mol
      ecules are consolidated in the form of polymeric chains extending along [010].
      R(3) (3)(10) ring motifs exist due to N-H?O and N-H?N hydrogen bonds.

PMID- 22606186
TI  - 3-Methyl-1-benzofuran-2-carbohydrazide.
AB  - In the asymmetric unit of the title benzofuran derivative, C(10)H(10)N(2)O(2),
      there are three crystallograpically independent mol-ecules, which are slightly
      twisted; the dihedral angle between the benzofuran ring system and the plane of
      the carbohydrazide unit is 8.64 (11) degrees  in one mol-ecule, whereas the
      dihedral angles are 9.58 (11) and 6.89 (10) degrees  in the other two mol-ecules.
      In the crystal, the three independent mol-ecules are linked to each other through
      N-H?N hydrogen bonds, forming a trimer. The trimers are further linked by weak N
      H?O and C-H?O hydrogen bonds into a three-dimensional network. pi-pi inter
      actions with centroid-centroid distances in the range 3.4928 (11)-3.8561 (10) A
      are also observed.

PMID- 22606187
TI  - Methyl 2-(2-bromo-benzyl-idene)-5-(4-hy-droxy-phen-yl)-7-methyl-3-oxo-2,3-dihydro
      5H-1,3-thia-zolo[3,2-a]pyrimidine-6-carboxyl-ate.
AB  - In the title compound, C(22)H(17)BrN(2)O(4)S, the central dihydropyrimidine ring,
      with a chiral C atom, is significantly puckered and adopts a half-chair
      conformation with the chiral C atom displaced from the mean plane of the
      remaining ring atoms by 0.305 (6) A. The hydroxy-phenyl ring is positioned
      axially to the pyrimidine ring and almost bisects it, the dihedral angle between
      the mean-planes of the two rings being 89.78 (12) degrees . The meth-oxy-carbonyl
      group is disordered over two sites with an occupancy ratio of 0.568 (5):0.432
      (5), resulting in a major and a minor conformer. In the crystal, O-H?N and C-H?S
      inter-actions result in sheets along the c axis. The supra-molecular assembly is
      stabilized by pi-pi stacking inter-actions between the 2-bromo-benzyl-idene and
      thia-zolopyrimidine rings [centroid-centroid distance = 3.632 (1) A]. In
      addition, C-H?pi inter-actions are also observed in the crystal structure.

PMID- 22606188
TI  - (E)-1-{4-[Bis(4-meth-oxy-phen-yl)meth-yl]piperazin-1-yl}-3-(4-eth-oxy-3-meth-oxy
      phen-yl)prop-2-en-1-one.
AB  - In the mol-ecule of the title compound, C(31)H(36)N(2)O(5), the piperazine ring
      displays a chair conformation. The dihedral angle between the benzene rings of
      the bis-(4-meth-oxy-phen-yl)methyl group is 83.42 (15) degrees . In the crystal,
      centrosymmetric-ally related mol-ecules are linked through pairs of C-H?O
      hydrogen bonds into dimers, generating an R(2) (2)(10) ring motif. The dimers are
      further connected into chains parallel to [2-10] by C-H?O hydrogen bonds
      involving the meth-oxy groups.

PMID- 22606189
TI  - Benzene-1,3,5-tricarbonyl trichloride.
AB  - In the title molecule, C(9)H(3)Cl(3)O(3), there are three short interactions
      involving the benzene H atoms and the chloro-formyl Cl atoms. In the crystal, mol
      ecules stack along the a axis with no significant non-bonded inter-actions.

PMID- 22606190
TI  - 2-Vinyl-pyridine-tris-(penta-fluoro-phen-yl)borane hexane monosolvate.
AB  - The title compound, C(7)H(7)N.B(C(6)F(5))(3).C(6)H(14), was obtained by the
      stoichiometric reaction of 2-vinyl-pyridine and tris-(penta-fluoro-phen-yl)borane
      in toluene. The formed adduct exhibits a restricted rotation along the B-N bond
      resulting in an asymmetry, which can be also observed in the (19)F NMR spectra.
      The B-N distance is equivalent to the distances found for 2-methyl-pyridine and 2
      ethyl-pyridine B(C(6)F(5))(3) adducts. For the final refinement, the
      contributions of disordered solvent mol-ecules were removed from the diffraction
      data with SQUEEZE in PLATON [van der Sluis & Spek (1990). Acta Cryst. A46, 194
      201; Spek (2009). Acta Cryst. D65, 148-155].

PMID- 22606191
TI  - 2-[4-(2-Hy-droxy-propan-2-yl)-1H-1,2,3-triazol-1-yl]phenol.
AB  - In the title compound, C(11)H(13)N(3)O(2), the 1,2,3-triazole ring and the phenol
      ring form a dihedral angle of 55.46 (5) degrees . In the crystal, inversion
      related mol-ecules associate through pairs of hy-droxy-phenol O-H?O hydrogen
      bonds, giving centrosymmetric cyclic dimers [graph set R(2) (2)(18)]. These
      dimers are linked into infinite chains along [001], giving an overall two
      dimensional network structure parallel to the bc plane through hy-droxy O-H?N and
      triazole C-H?N hydrogen bonds.

PMID- 22606192
TI  - 6-Methyl-ideneandrost-4-ene-3,17-dione.
AB  - In the title compound, C(20)H(26)O(2), which is the 6-methyl-ene derivative of
      androstenedione and a synthetic percursor of exemestane, the steroid A ring
      approximates to a sofa (or envelope) conformation, with the methyl-ene group
      adjacent to the link to the B ring lying out of the plane of the other atoms. The
      B and C rings have slightly flattened chair conformations and the D ring is an
      envelope, with the CH group forming the flap. In the crystal, mol-ecules are
      linked by two distinct C-H?O hydrogen bonds, involving acidic H atoms close to
      C=C and C=O double bonds.

PMID- 22606193
TI  - 3-Anilino-1-(isopropyl-amino)-propan-2-ol.
AB  - The title compound, C(12)H(20)N(2)O, was obtained by the reaction of N-(oxiran-2
      ylmeth-yl)aniline and propan-2-amine. In the crystal, mol-ecules are linked by O
      H?N and N-H?O hydrogen bonds into chains parallel to the b axis.

PMID- 22606194
TI  - 7'-Phenyl-1',3',5',6',7',7a'-hexa-hydro-dipiro[acenaphthyl-ene-1,5'-pyrrolo-[1,2
      c]thia-zole-6',2''-indane]-2,1''(1H)-dione.
AB  - In the title compound, C(31)H(23)NO(2)S, the pyrrolidine ring adopts an envelope
      conformation (with the spiro C atom as the flap), while the thia-zolidine ring
      and the two cyclo-pentane rings adopt twisted conformations. The mean plane
      through the hexa-hydro-pyrrolo-[1,2-c]thia-zole ring [r.m.s deviation = 0.400 (1)
      A] forms dihedral angles of 76.83 (4), 80.70 (5) and 79.00 (4) degrees  with the
      benzene ring and the mean planes of the dihydro-acenaphthyl-ene and the dihydro
      indene rings, respectively. In the crystal, mol-ecules are linked by C-H?O
      hydrogen bonds into sheets lying parallel to the bc plane. One of the ketone O
      atoms accepts three such bonds. Weak C-H?pi inter-actions are also observed.

PMID- 22606195
TI  - 1-(2-Bromo-phen-yl)-3-(4-chloro-butano-yl)thio-urea.
AB  - The asymmetric unit of the title compound, C(11)H(12)BrClN(2)OS, consists of two
      crystallographically independent mol-ecules. In each mol-ecule, the butano-ylthio
      urea unit is nearly planar, with maximum deviations of 0.1292 (19) and 0.3352
      (18) A from the mean plane defined by nine non-H atoms, and is twisted relative
      to the terminal benzene ring with dihedral angles of 69.26 (7) and 82.41 (7)
      degrees . An intra-molecular N-H?O hydrogen bond generates an S(6) ring motif in
      each butano-ylthio-urea unit. In the crystal, N-H?O hydrogen bonds link the two
      independent mol-ecules together, forming an R(2) (2)(12) ring motif. The mol
      ecules are further connected into a tape along the c axis via N-H?S and C-H?S
      hydrogen bonds.

PMID- 22606196
TI  - 2-Azido-1-(4-fluoro-phen-yl)ethanone.
AB  - The crystal structure of the title compound, C(8)H(6)FN(3)O, is stabilized by C
      H?O hydrogen bonds, which link the mol-ecules into chains running parallel to the
      a axis.

PMID- 22606197
TI  - 4-Bromo-N-phenyl-benzamide.
AB  - The mol-ecule of the title benzamide derivative, C(13)H(10)BrNO, is twisted with
      the dihedral angle between the phenyl and 4-bromo-phenyl rings being 58.63 (9)
      degrees . The central N-C=O plane makes dihedral angles of 30.2 (2) and 29.2 (2)
      degrees  with the phenyl and 4-bromo-phenyl rings, respectively. In the crystal,
      mol-ecules are linked by N-H?O hydrogen bonds into chains along [100]. C-H?pi
      contacts combine with the N-H?O hydrogen bonds, to form a three-dimensional
      network.

PMID- 22606198
TI  - (E)-3-Anilino-2-benzoyl-3-(methyl-sulfan-yl)acrylonitrile.
AB  - In the title acrylonitrile derivative, C(17)H(14)N(2)OS, the central amino-acryl
      aldehyde O=C-C=C-NH unit, wherein an intra-molecular N-H?O hydrogen bond
      generates an S(6) ring motif, is approximately planar, with an r.m.s. deviation
      of 0.0234 (2) A for the five non-H atoms. This plane makes dihedral angles of
      41.04 (9) and 84.86 (10) degrees  with the two phenyl rings. The dihedral angle
      between the two phenyl rings is 54.82 (10) degrees . An intra-molecular C-H?N
      hydrogen bond is also present. In the crystal, weak C-H?pi and pi-pi inter
      actions, with a centroid-centroid distance of 3.8526 (14) A, are observed.

PMID- 22606199
TI  - N-Cyclo-hexyl-N-{[3-(4,6-dimeth-oxy-pyrimidin-2-yl-oxy)pyridin-2-yl]meth-yl}4,6
      dimeth-oxy-pyrimidin-2-amine.
AB  - In the title compound, C(24)H(30)N(6)O(5), the cyclo-hexyl ring adopts a chair
      conformation, while the remainder of the mol-ecule adopts a U-shape. The dihedral
      angles between the pyridine ring and the pendant pyrimidine rings are 69.04 (12)
      and 75.99 (9) degrees . The two pyrimidine rings, however, are nearly parallel to
      one another, with a dihedral angle of 8.56 (15) degrees  between them. They are
      also involved in an intra-molecular pi-pi stacking inter-action with a distance
      of 3.6627 (18) A between the ring centroids. In the crystal, C-H?O contacts link
      the mol-ecules into chains along the b axis.

PMID- 22606200
TI  - (Z)-2-(5-Chloro-2-oxoindolin-3-yl-idene)-N-methyl-hydrazinecarbothio-amide.
AB  - In the title compound, C(10)H(9)ClN(4)OS, an intra-molecular N-H?O hydrogen
      bonding inter-action and an N-H?N inter-action generate ring motifs [graph sets
      S(6) and S(5), respectively]. In the crystal, mol-ecules form a chain through N
      H?O hydrogen bonds, and these are extended by N-H?S hydrogen-bonding inter
      actions into an infinite three-dimensional network. The crystal structure also
      exhibits weak C-H?pi inter-actions.

PMID- 22606201
TI  - Evaluation of patient satisfaction of an outpatient colonoscopy service in an
      asian tertiary care hospital.
AB  - Aim. To evaluate patient satisfaction towards an outpatient colonoscopy service
      and analyze areas of dissatisfaction for potential improvement. Method.
      Consecutive patients attending the outpatient diagnostic colonoscopy service in
      University of Malaya Medical Centre between 1st February and 31th July 2010 were
      interviewed using a questionnaire modified from the modified Group Health
      Association of America-9 (mGHAA-9) questionnaire. Favorable/unfavorable responses
      to each question, contribution of each question to unfavorable responses, and
      effect of waiting times on favorable/unfavorable response rates were analyzed.
      Results. Interview was carried out on 426 patients (52.1% men). Mean age +/-
      standard deviation was 61.3 +/- 12.9 years old. Mean waiting times for
      colonoscopy appointment and on colonoscopy day were 3.8 +/- 2.7 months and 1.1 +/
      0.8 hours, respectively. The main factors that contributed to unfavorable
      responses were bowel preparation followed by waiting times for colonoscopy
      appointment and on colonoscopy day (32.3%, 27.5%, and 19.6%, resp.). Favorable
      responses diminished to undesirable levels when waiting times for colonoscopy
      appointment and on colonoscopy day exceeded 1 month and 1 hour, respectively.
      Conclusion. Bowel preparation and waiting times were main factors for patient
      dissatisfaction. Waiting times for colonoscopy appointment and on colonoscopy day
      should not exceed 1 month and 1 hour, respectively, to maintain acceptable levels
      of patient satisfaction.

PMID- 22606202
TI  - Microtensile bond strength of self-adhesive luting cements to ceramics.
AB  - The purpose of this paper was to compare the bond strengths of the self-adhesive
      luting cements between ceramics and resin cores and examine their relation to the
      cement thickness. Three self-adhesive luting cements (Smartcem, Maxcem, and G
      CEM) and a resin cement (Panavia F 2.0) for control were used in the paper. The
      thickness of the cements was controlled in approximately 25, 50, 100, or 200 MUm.
      Each 10 specimens were made according to the manufacturers' instructions and
      stored in water at 37 degrees C. After 24 hours, microtensile bond strength
      (MUTBS) was measured. There were significant differences in cements. Three self
      adhesive cements showed significantly lower MUTBSs than control that required
      both etching and priming before cementation (Tukey, P < 0.05). The cement
      thickness of 50 or 100 MUm tended to induce the highest MUTBSs for each self
      adhesive luting cements though no difference was found.

PMID- 22606203
TI  - Ultra high-mass resolution paper spray by fourier transform ion cyclotron
      resonance mass spectrometry.
AB  - Paper Spray Ionization is an atmospheric pressure ionization technique that
      utilizes an offline electro-osmotic flow to generate ions off a paper medium.
      This technique can be performed on a Bruker SolariX Fourier transform ion
      cyclotron resonance mass spectrometer by modifying the existing nanospray source.
      High-resolution paper spray spectra were obtained for both organic and biological
      samples to demonstrate the benefit of linking the technique with a high
      resolution mass analyzer. Error values in the range 0.23 to 2.14 ppm were
      obtained for calf lung surfactant extract with broadband mass resolving power
      (m/Deltam(50%)) above 60,000 utilizing an external calibration standard.

PMID- 22606204
TI  - The Prevalence of Aflatoxinogenic Aspergillus parasiticus in Jordan.
AB  - Aflatoxins are potent carcinogens and produced by almost all Aspergillus
      parasiticus isolates and about 35% of Aspergillus flavus isolates. Chemical
      methods are used for detection of aflatoxins in food and feed. These methods
      cannot detect aflatoxinogenic fungi in samples, which contain undetectable
      amounts of aflatoxins. The objective of this research work was to ascertain the
      importance of molecular and microbiological methods in detection of
      aflatoxinogenic fungus A. parasiticus in food and feed samples in Jordan.
      Specific media for the detection of aflatoxins showed the prevalence of A.
      parasiticus (6-22%) in contaminated food and feed samples. HPLC method confirmed
      the presence of aflatoxins B1, B2, G1, and G2 in food sample contaminated with A.
      parasiticus. Primer set OmtBII-F and OmtBII-R amplified DNA fragment of 611 base
      pairs from genomic DNA of aflatoxinogenic A. parasiticus isolated from food and
      feed samples but could not amplify DNA fragment of nonaflatoxinogenic A. flavus.
      The results of this study showed the prevalence of aflatoxinogenic A. parasiticus
      in food and feed samples in Jordan and give further evidence of suitability of
      microbiological and molecular methods in detection of aflatoxins, which are
      reliable low-cost approach to determine food and feed biosafety.

PMID- 22606205
TI  - Human Muscle Progenitor Cells Displayed Immunosuppressive Effect through Galectin
      1 and Semaphorin-3A.
AB  - In human skeletal muscle, myoblasts represent the main population of myogenic
      progenitors. We previously showed that, beside their myogenic differentiation
      capacities, myoblasts also differentiate towards osteogenic and chondrogenic
      lineages, some properties generally considered being hallmarks of mesenchymal
      stem cells (MSCs). MSCs are also characterized by their immunosuppressive
      potential, through cell-cell contacts and soluble factors, including
      prostaglandin E-2 (PGE-2), transforming growth factor-beta1 (TGF-beta1),
      interleukine-10, or indoleamine 2,3-dioxygenase. We and others also reported that
      Galectin-1 (Gal-1) and Semaphorin-3A (Sema-3A) were involved in MSCs-mediated
      immunosuppression. Here, we show that human myoblasts induce a significant and
      dose-dependant proliferation inhibition, independently of PGE-2 and TGF-beta1.
      Our experiments revealed that myoblasts, in culture or in situ in human muscles,
      expressed and secreted Gal-1 and Sema-3A. Furthermore, myoblasts
      immunosuppressive functions were reverted by using blocking antibodies against
      Gal-1 or Sema-3A. Together, these results demonstrate an unsuspected
      immunosuppressive effect of myoblasts that may open new therapeutic perspectives.

PMID- 22606206
TI  - Curcumin-induced apoptosis in human hepatocellular carcinoma j5 cells: critical
      role of ca(+2)-dependent pathway.
AB  - The antitumor effects of curcumin, a natural biologically active compound
      extracted from rhizomes of Curcuma longa, have been studied in many cancer cell
      types including human hepatocellular carcinoma (HCC). Here, we investigated the
      effects of Ca(2+) on curcumin-induced apoptosis in human HCC J5 cells. The
      abrogation of mitochondrial membrane potential (DeltaPsi(m)), the increase of
      reactive oxygen species (ROS) production, and calcium release were demonstrated
      with flow cytometry as early as 15 minutes after curcumin treatment. In addition,
      an increase level of cytochrome c in the cytoplasm which led to DNA fragmentation
      was observed. To verify the role of Ca(2+) in curcumin-induced apoptosis, 1,2
      bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), an intracellular
      calcium chelator, was applied. Cell viability was increased, but DeltaPsi(m), ROS
      production, activation of caspase 3, and cell death were decreased in J5 cells
      pretreated with BAPTA for 2 h followed by the treatment of 25 MUM curcumin. These
      results suggest that the curcumin-induced apoptosis in human HCC J5 cells is via
      mitochondria-dependent pathway and is closely related to the level of
      intracellular accumulation of calcium.

PMID- 22606207
TI  - Outcome measures of chinese herbal medicine for coronary heart disease: an
      overview of systematic reviews.
AB  - Objective. The aim of this overview was to summarize the outcome measures of
      Chinese herbal medicine (CHM) as the treatment of coronary heart disease (CHD)
      based on available systematic reviews (SRs), so as to display the current
      situation and evaluate the potential benefits and advantages of CHM on CHD.
      Methods. An extensive search included the Cochrane Database of Systematic
      Reviews, MEDLINE, and 4 databases in Chinese. SRs of CHM for CHD were included.
      Besides evaluating and summarizing the outcome measures, we also estimated the
      quality of the included reviews by PRISMA (preferred reporting items for
      systematic reviews and meta-analyses). Data were extracted according to
      predefined inclusion criteria by two independent reviewers. Results. 46 articles
      were included. 20 kinds of CHM were reviewed. 7 SRs were concerned with
      myocardial infarction (MI), 38 SRs were related to angina pectoris. 11 SRs had
      primary endpoints, while others focused on secondary endpoints to evaluate CHM
      for CHD such as angina pectoris and electrocardiogram (ECG). One SR reported more
      adverse effects of CHM for CHD and of the SRs analyzed quality of life. Many CHM
      appeared to have significant effect on improving symptoms, ECG, biomarkers and so
      on. However, most SRs failed to make a definite conclusion for the effectiveness
      of CHM in CHD patients due specifically to the poor evidence. And according to
      PRISMA we found most of the trials in the SRs were of low quality. Conclusion.
      Primary endpoints were not used widely. The benefits of CHM for CHD need to be
      confirmed in the future with RCTs of more persuasive primary endpoints and high
      quality SRs.

PMID- 22606208
TI  - The effect of abdominal radical trachelectomy on ovarian reserve: serial changes
      in serum anti-mullerian hormone levels.
AB  - AIM: To evaluate the effect of abdominal radical trachelectomy on ovarian reserve
      and compare it with abdominal radical hysterectomy and a control group that did
      not have surgery. METHOD: We enrolled eighteen women who had abdominal radical
      trachelectomy with pelvic lymphadenectomy and sixteen patients who had abdominal
      radical hysterectomy for this study. Ten thousand one hundred eighty-six women
      were also included as a control group for comparison. The Mann-Whitney U test was
      used for comparison of patient characteristics and comparison of serum anti
      Mullerian hormone levels between the three groups. RESULTS: Serum anti-Mullerian
      hormone levels in patients with abdominal radical trachelectomy were
      significantly higher than those of patients with abdominal radical hysterectomy
      (P<0.05). Serum anti-Mullerian hormone levels in the abdominal radical
      hysterectomy group were significantly lower than those in the control group
      (P=0.02), with no significant difference between the abdominal radical
      trachelectomy and control groups. These data indicated that abdominal radical
      trachelectomy did not affect ovarian function with respect to ovarian reserve and
      the response to ovarian stimulation. CONCLUSIONS: Serum anti-Mullerian hormone
      levels could be useful as a marker of ovarian reserve after abdominal radical
      trachelectomy. It is important to avoid postoperative complications causing a
      reduction in ovarian function to accomplish fertility-sparing surgery.

PMID- 22606209
TI  - Establishment of human ultra-low passage colorectal cancer cell lines using
      spheroids from fresh surgical specimens suitable for in vitro and in vivo
      studies.
AB  - Colorectal cancer (CRC) holds the third highest incidence and cancer related
      mortality rate among men and women in the United States. Unfortunately, there has
      been little progression made in the treatment of this deadly disease once it has
      spread beyond the colon. It has been hypothesize that colon cancer stem cells are
      implicated in CRC carcinogenesis, metastasis, and therapeutic resistance. One of
      the difficulties in testing these hypotheses is the current use of established
      high-passage cancer cell lines. Long term, high-passage established cell lines
      have cells with stem like properties as they propagate almost indefinitely. These
      cells are thought to be different than the original cancer stem cells in fresh
      tumors. In order to investigate cancer stem cells, and molecularly profiling
      tumors with high fidelity to the original primary tumor, one needs to establish
      suitable primary ultra-low passage cell lines from fresh surgical specimens. Here
      we report the establishment of tumor initiating colon cancer ultra-low passage
      cell lines by a combination of gentle mechanical, enzymatic dissociation,
      spheroid formation, and followed by two generation xenografts from fresh tumors
      obtained at time of operation. Tumors generated were characterized by morphology,
      flow cytometry, immunofluorescence, and by gene expression. In the future, such a
      technology can be used to produce expeditiously enough material to test for
      mutations, genetic signatures and molecular subtyping readily available for
      clinical therapeutic decision making.

PMID- 22606210
TI  - Current Practice Patterns Regarding the Conduct of Thyroidectomy and
      Parathyroidectomy amongst Surgeons - A Survey Study.
AB  - BACKGROUND: Heterogeneity of surgical care exists among surgeons regarding the
      conduct of thyroidectomy and parathyroidectomy. AIM: To identify the current
      patterns of technical conduct of operation amongst surgeons performing
      thyroidectomy or parathyroidectomy. METHODS: A survey was designed and beta
      tested on five surgical oncologists for face validity and usability. The final
      version of this survey was constructed and disseminated using the professional
      version of the internet-based survey mechanism Survey Monkey and consisted of two
      eligibility questions and 22 questions regarding thyroidectomy/parathyroidectomy
      treatment patterns. The survey was disseminated electronically to American
      Association of Endocrine Surgeons (AAES) and American College of Surgeons (ACS)
      members. Survey results were collected, tabulated and analyzed. Responses among
      groups were compared using two sample T- tests. Significant responses were
      subsequently analyzed in generalized linear models to ascertain if significance
      remained with control of covariates. RESULTS: Of 420 initial web survey visits,
      236 (56.2%) surveys were completed. The majority of respondents reported being
      'fellowship trained', experienced and 'high-volume' surgeons. The most common
      fellowship trainings were endocrine (46%), oncology (22%), head & neck (13%), or
      combinations of the three fellowships (14%). Most surgeons reported that they
      dissect the course of the recurrent laryngeal nerve (RLN) without using
      neuromonitoring. Nearly a third of respondents reported routinely using the
      Harmonic scalpel during the conduct of the operations. Significant differences
      emerged regarding operative technique according to residency training type,
      fellowship training, surgeon volume, and practice setting, but only those
      associated with residency training type and annual surgeon surgical volume
      remained significant within generalized linear models. CONCLUSION: Most surgeons
      who responded to this survey do not routinely use RLN neuromonitoring and most
      dissect the RLN during thyroidectomy. There are multiple variations in technique
      according to surgical training, surgeon volume, experience, and practice setting;
      however, only differences by residency training type and surgeon volume remained
      correlated significantly to surgeons' approaches to thyroidectomy and
      parathyroidectomy in multivariate analysis. These data may be useful for surgeons
      reflecting upon their individual practice, as well as for further defining
      current standards of practice from a medico legal perspective.

PMID- 22606211
TI  - Patient Satisfaction with Physician Discussions of Treatment Impact on Fertility,
      Menopause and Sexual Health among Pre-menopausal Women with Cancer.
AB  - PURPOSE: Pre-menopausal women with cancer are at risk of therapy-associated
      infertility, premature menopause, and sexual dysfunction. However, it is unknown
      whether oncologists adequately address these risks during treatment planning. We
      conducted a study to evaluate physician-patient discussions addressing the impact
      of cancer treatment and actual treatment effects on fertility, menopause status,
      and general sexual health. METHODS: A questionnaire was administered in four
      oncology clinics specializing in breast, gynecologic, general hematology
      oncology, and blood and marrow transplantation (BMT) cancer care at a single
      institution. Eligible participants were pre-menopausal at the time of diagnosis
      and either actively receiving or within 24 months from completion of treatment.
      Participants completed the questionnaire at enrollment and at 1-year follow-up.
      RESULTS: Of the 104 eligible women, a majority were satisfied with the quality
      (68%) and length (66%) of reproductive health discussions, with the highest
      satisfaction levels in the gynecologic cancer clinic (85%) and the lowest levels
      in the BMT clinic (53%). Fertility preservation was desired by 20% of women,
      including some >40 years old. Women were more interested in discussing treatment
      impact on menopause status and sexual health than fertility. Rates of discussions
      on treatment impact on sexual health were low despite 77% of women reporting
      severe sexual dysfunction at 1-year follow-up. CONCLUSIONS: One-third of women
      are dissatisfied with the quality and length of discussions regarding the impact
      of cancer treatment on reproductive health. There is notably inadequate
      counseling on the effect of treatment on fertility in women > 40 and on sexual
      function in all women. Oncologists must offer better resources and improve
      communication on the effect of treatment on reproductive health to pre-menopausal
      women with cancer.

PMID- 22606212
TI  - Reporter gene imaging in therapy and diagnosis.
AB  - Noninvasive molecular imaging using reporter genes is a relatively recent field
      in biomedical imaging that holds great promises for disease diagnosis and
      therapy. As modern medicine is moving towards personalized medicine, targeted
      biomolecule based therapies is gaining popularity that requires careful and
      systematic validation. Reporter genes have emerged as important generalizable
      tools to overcome the shortcomings of direct evaluation of individual
      biomolecules and are being applied in various fields such as cell therapy, stem
      cell therapy, immune therapy, viral gene delivery through optical, radionuclide,
      magnetic resonance imaging techniques. New approaches to image protein-protein
      interaction, protein phosphorylation, protein folding that are crucial parameters
      for theranostic study using reporter genes are being developed. All these new
      technologies and relevant preclinical and clinical researches will determine the
      success of early detection and personalized therapy in the future.

PMID- 22606213
TI  - Indocyanine green fluorescence imaging for evaluation of uterine blood flow in
      cynomolgus macaque.
AB  - BACKGROUND: Uterine blood flow is an important factor in uterine viability, but
      the number of blood vessels required to maintain viability is uncertain. In this
      study, indocyanine green (ICG) fluorescence imaging was used to examine uterine
      hemodynamics and vessels associated with uterine blood flow in cynomolgus
      macaque. METHODS: The uterus of a female cynomolgus macaque was cut from the
      vaginal canal to mimic a situation during trachelectomy or uterine
      transplantation surgery in which uterine perfusion is maintained only with
      uterine and ovarian vessels. Intraoperative uterine hemodynamics was observed
      using ICG fluorescence imaging under conditions in which various nutrient vessels
      were selected by clamping of blood vessels. A time-intensity curve was plotted
      using imaging analysis software to measure the T(max) of uterine perfusion for
      selected blood vessel patterns. Open surgery was performed with the uterus
      receiving nutritional support only from uterine vessels on one side. The size of
      the uterus after surgery was monitored using transabdominal ultrasonography.
      RESULTS: The resulting time-intensity curves displayed the average intensity in
      the regions of the uterine corpus and uterine cervix, and in the entire uterus.
      Analyses of the uterine hemodynamics in the cynomolgus macaque showed that
      uterine vessels were significantly related to uterine perfusion (P=0.008),
      whereas ovarian vessels did not have a significant relationship (P=0.588). When
      uterine vessels were clamped, ovarian vessels prolonged the time needed to reach
      perfusion maximum. Postoperative transabdominal ultrasonography showed that the
      size of the uterus was not changed 2 months after surgery, with recovery of
      periodic menstruation. The cynomolgus macaque has got pregnant with favorable
      fetus well-being. CONCLUSION: Uterine vessels may be responsible for uterine
      blood flow, and even one uterine vessel may be sufficient to maintain uterine
      viability in cynomolgus macaque. Our results show that ICG fluorescence imaging
      is useful for evaluation of uterine blood flow since this method allows real-time
      observation of uterine hemodynamics.

PMID- 22606218
TI  - Genes associated with honey bee behavioral maturation affect clock-dependent and 
      independent aspects of daily rhythmic activity in fruit flies.
AB  - BACKGROUND: In the honey bee, the age-related and socially regulated transition
      of workers from in-hive task performance (e.g., caring for young) to foraging
      (provisioning the hive) is associated with changes in many behaviors including
      the 24-hour pattern of rhythmic activity. We have previously shown that the hive
      bee to forager transition is associated with extensive changes in brain gene
      expression. In this study, we test the possible function of a subset of these
      genes in daily rhythmic activity pattern using neural-targeted RNA interference
      (RNAi) of an orthologous gene set in Drosophila melanogaster. PRINCIPAL FINDINGS:
      Of 10 genes tested, knockdown of six affected some aspect of locomotor activity
      under a 12 h:h light:dark regime (LD). Inos affected anticipatory activity
      preceding lights-off, suggesting a possible clock-dependent function. BM-40
      SPARC, U2af50 and fax affected peak activity at dawn without affecting
      anticipation or overall inactivity (proportion of 15-min intervals without
      activity), suggesting that these effects may depend on the day-night light cycle.
      CAH1 affected overall inactivity. The remaining gene, abl, affected peak activity
      levels but was not clearly time-of-day-specific. No gene tested affected length
      of period or strength of rhythmicity in constant dark (DD), suggesting that these
      genes do not act in the core clock. SIGNIFICANCE: Taking advantage of Drosophila
      molecular genetic tools, our study provides an important step in understanding
      the large set of gene expression changes that occur in the honey bee transition
      from hive bee to forager. We show that orthologs of many of these genes influence
      locomotor activity in Drosophila, possibly through both clock-dependent and 
      independent pathways. Our results support the importance of both circadian clock
      and direct environmental stimuli (apart from entrainment) in shaping the bee's 24
      hour pattern of activity. Our study also outlines a new approach to dissecting
      complex behavior in a social animal.

PMID- 22606219
TI  - A novel high-throughput assay for islet respiration reveals uncoupling of rodent
      and human islets.
AB  - BACKGROUND: The pancreatic beta cell is unique in its response to nutrient by
      increased fuel oxidation. Recent studies have demonstrated that oxygen
      consumption rate (OCR) may be a valuable predictor of islet quality and long term
      nutrient responsiveness. To date, high-throughput and user-friendly assays for
      islet respiration are lacking. The aim of this study was to develop such an assay
      and to examine bioenergetic efficiency of rodent and human islets.
      METHODOLOGY/PRINCIPAL FINDINGS: The XF24 respirometer platform was adapted to
      islets by the development of a 24-well plate specifically designed to confine
      islets. The islet plate generated data with low inter-well variability and
      enabled stable measurement of oxygen consumption for hours. The F1F0 ATP synthase
      blocker oligomycin was used to assess uncoupling while rotenone together with
      myxothiazol/antimycin was used to measure the level of non-mitochondrial
      respiration. The use of oligomycin in islets was validated by reversing its
      effect in the presence of the uncoupler FCCP. Respiratory leak averaged to 59%
      and 49% of basal OCR in islets from C57Bl6/J and FVB/N mice, respectively. In
      comparison, respiratory leak of INS-1 cells and C2C12 myotubes was measured to
      38% and 23% respectively. Islets from a cohort of human donors showed a
      respiratory leak of 38%, significantly lower than mouse islets.
      CONCLUSIONS/SIGNIFICANCE: The assay for islet respiration presented here provides
      a novel tool that can be used to study islet mitochondrial function in a
      relatively high-throughput manner. The data obtained in this study shows that
      rodent islets are less bioenergetically efficient than human islets as well as
      INS1 cells.

PMID- 22606220
TI  - The role of TNF-alpha in mice with type 1- and 2- diabetes.
AB  - BACKGROUND: Previously, we have demonstrated that short-term treatment of new
      onset diabetic Non-obese diabetic (NOD) mice, mice that are afflicted with both
      type 1 (T1D) and type 2 (T2D) diabetes with either Power Mix (PM) regimen or
      alpha1 antitrypsin (AAT) permanently restores euglycemia, immune tolerance to
      self-islets and normal insulin signaling. METHODOLOGY AND PRINCIPAL FINDINGS: To
      search for relevant therapeutic targets, we have applied genome wide
      transcriptional profiling and systems biology oriented bioinformatics analysis to
      examine the impact of the PM and AAT regimens upon pancreatic lymph node (PLN)
      and fat, a crucial tissue for insulin dependent glucose disposal, in new onset
      diabetic non-obese diabetic (NOD) mice. Systems biology analysis identified tumor
      necrosis factor alpha (TNF-alpha) as the top focus gene hub, as determined by the
      highest degree of connectivity, in both tissues. In PLNs and fat, TNF-alpha
      interacted with 53% and 32% of genes, respectively, associated with reversal of
      diabetes by previous treatments and was thereby selected as a therapeutic target.
      Short-term anti-TNF-alpha treatment ablated a T cell-rich islet-invasive and beta
      cell-destructive process, thereby enhancing beta cell viability. Indeed anti-TNF
      alpha treatment induces immune tolerance selective to syngeneic beta cells. In
      addition to these curative effects on T1D anti-TNF-alpha treatment restored in
      vivo insulin signaling resulting in restoration of insulin sensitivity.
      CONCLUSIONS: In short, our molecular analysis suggested that PM and AAT both may
      act in part by quenching a detrimental TNF-alpha dependent effect in both fat and
      PLNs. Indeed, short-term anti-TNF-alpha mAb treatment restored enduring
      euglycemia, self-tolerance, and normal insulin signaling.

PMID- 22606221
TI  - Structural insights into human peroxisome proliferator activated receptor delta
      (PPAR-delta) selective ligand binding.
AB  - Peroxisome proliferator activated receptors (PPARs delta, alpha and gamma) are
      closely related transcription factors that exert distinct effects on fatty acid
      and glucose metabolism, cardiac disease, inflammatory response and other
      processes. Several groups developed PPAR subtype specific modulators to trigger
      desirable effects of particular PPARs without harmful side effects associated
      with activation of other subtypes. Presently, however, many compounds that bind
      to one of the PPARs cross-react with others and rational strategies to obtain
      highly selective PPAR modulators are far from clear. GW0742 is a synthetic ligand
      that binds PPARdelta more than 300-fold more tightly than PPARalpha or PPARgamma
      but the structural basis of PPARdelta:GW0742 interactions and reasons for strong
      selectivity are not clear. Here we report the crystal structure of the
      PPARdelta:GW0742 complex. Comparisons of the PPARdelta:GW0742 complex with
      published structures of PPARs in complex with alpha and gamma selective agonists
      and pan agonists suggests that two residues (Val312 and Ile328) in the buried
      hormone binding pocket play special roles in PPARdelta selective binding and
      experimental and computational analysis of effects of mutations in these residues
      confirms this and suggests that bulky substituents that line the PPARalpha and
      gamma ligand binding pockets as structural barriers for GW0742 binding. This
      analysis suggests general strategies for selective PPARdelta ligand design.

PMID- 22606222
TI  - Exploring protein dynamics space: the dynasome as the missing link between
      protein structure and function.
AB  - Proteins are usually described and classified according to amino acid sequence,
      structure or function. Here, we develop a minimally biased scheme to compare and
      classify proteins according to their internal mobility patterns. This approach is
      based on the notion that proteins not only fold into recurring structural motifs
      but might also be carrying out only a limited set of recurring mobility motifs.
      The complete set of these patterns, which we tentatively call the dynasome, spans
      a multi-dimensional space with axes, the dynasome descriptors, characterizing
      different aspects of protein dynamics. The unique dynamic fingerprint of each
      protein is represented as a vector in the dynasome space. The difference between
      any two vectors, consequently, gives a reliable measure of the difference between
      the corresponding protein dynamics. We characterize the properties of the
      dynasome by comparing the dynamics fingerprints obtained from molecular dynamics
      simulations of 112 proteins but our approach is, in principle, not restricted to
      any specific source of data of protein dynamics. We conclude that: 1. the
      dynasome consists of a continuum of proteins, rather than well separated classes.
      2. For the majority of proteins we observe strong correlations between structure
      and dynamics. 3. Proteins with similar function carry out similar dynamics, which
      suggests a new method to improve protein function annotation based on protein
      dynamics.

PMID- 22606223
TI  - A regulatory potential of the Xist gene promoter in vole M. rossiaemeridionalis.
AB  - X chromosome inactivation takes place in the early development of female mammals
      and depends on the Xist gene expression. The mechanisms of Xist expression
      regulation have not been well understood so far. In this work, we compared Xist
      promoter region of vole Microtus rossiaemeridionalis and other mammalian species.
      We observed three conserved regions which were characterized by computational
      analysis, DNaseI in vitro footprinting, and reporter construct assay. Regulatory
      factors potentially involved in Xist activation and repression in voles were
      determined. The role of CpG methylation in vole Xist expression regulation was
      established. A CTCF binding site was found in the 5' flanking region of the Xist
      promoter on the active X chromosome in both males and females. We suggest that
      CTCF acts as an insulator which defines an inactive Xist domain on the active X
      chromosome in voles.

PMID- 22606224
TI  - Factors associated with bovine neonatal pancytopenia (BNP) in calves: a case
      control study.
AB  - Bovine neonatal pancytopenia (BNP; previously known as idiopathic haemorrhagic
      diathesis and commonly known as bleeding calf syndrome) is a novel haemorrhagic
      disease of young calves which has emerged in a number of European countries
      during recent years. Data were retrospectively collected during June to November
      2010 for 56 case calves diagnosed with BNP between 17 March and 7 June of the
      same year. These were compared with 58 control calves randomly recruited from
      herds with no history of BNP. Multivariable logistic regression analysis showed
      that increased odds of a calf being a BNP case were associated with its dam
      having received PregSure(r) BVD (Pfizer Animal Health) vaccination prior to the
      birth of the calf (odds ratio (OR) 40.78, p<0.001) and its herd of origin being
      located in Scotland (OR 9.71, p = 0.006). Decreased odds of a calf being a BNP
      case were associated with the calf having been kept outside (OR 0.11, p = 0.006).
      The longer that a cattle herd had been established on the farm was also
      associated with decreased odds of a calf in that herd being a BNP case (OR 0.97,
      p = 0.011).

PMID- 22606225
TI  - Effects of aluminum oxide nanoparticles on the growth, development, and microRNA
      expression of tobacco (Nicotiana tabacum).
AB  - Nanoparticles are a class of newly emerging environmental pollutions. To date,
      few experiments have been conducted to investigate the effect nanoparticles may
      have on plant growth and development. It is important to study the effects
      nanoparticles have on plants because they are stationary organisms that cannot
      move away from environmental stresses like animals can, therefore they must
      overcome these stresses by molecular routes such as altering gene expression.
      microRNAs (miRNA) are a newly discovered, endogenous class of post
      transcriptional gene regulators that function to alter gene expression by either
      targeting mRNAs for degradation or inhibiting mRNAs translating into proteins.
      miRNAs have been shown to mediate abiotic stress responses such as drought and
      salinity in plants by altering gene expression, however no study has been
      performed on the effect of nanoparticles on the miRNA expression profile;
      therefore our aim in this study was to classify if certain miRNAs play a role in
      plant response to Al(2)O(3) nanoparticle stress. In this study, we exposed
      tobacco (Nicotiana tabacum) plants (an important cash crop as well as a model
      organism) to 0%, 0.1%, 0.5%, and 1% Al(2)O(3) nanoparticles and found that as
      exposure to the nanoparticles increased, the average root length, the average
      biomass, and the leaf count of the seedlings significantly decreased. We also
      found that miR395, miR397, miR398, and miR399 showed an extreme increase in
      expression during exposure to 1% Al(2)O(3) nanoparticles as compared to the other
      treatments and the control, therefore these miRNAs may play a key role in
      mediating plant stress responses to nanoparticle stress in the environment. The
      results of this study show that Al(2)O(3) nanoparticles have a negative effect on
      the growth and development of tobacco seedlings and that miRNAs may play a role
      in the ability of plants to withstand stress to Al(2)O(3) nanoparticles in the
      environment.

PMID- 22606226
TI  - Genetic polymorphisms in CYP2E1: association with schizophrenia susceptibility
      and risperidone response in the Chinese Han population.
AB  - BACKGROUND: CYP2E1 is a member of the cytochrome P450 superfamily, which is
      involved in the metabolism and activation of both endobiotics and xenobiotics.
      The genetic polymorphisms of CYP2E1 gene (Chromosome 10q26.3, Accession Number
      NC_000010.10) are reported to be related to the development of several mental
      diseases and to be involved in the clinical efficacy of some psychiatric
      medications. We investigated the possible association of CYP2E1 polymorphisms
      with susceptibility to schizophrenia in the Chinese Han Population as well as the
      relationship with response to risperidone in schizophrenia patients. METHODS: In
      a case-control study, we identified 11 polymorphisms in the 5' flanking region of
      CYP2E1 in 228 schizophrenia patients and 384 healthy controls of Chinese Han
      origin. From among the cases, we chose 130 patients who had undergone 8 weeks of
      risperidone monotherapy to examine the relationship between their response to
      risperidone and CYP2E1 polymorphisms. Clinical efficacy was assessed using the
      Brief Psychiatric Rating Scale (BPRS). RESULTS: Statistically significant
      differences in allele or genotype frequencies were found between cases and
      controls at rs8192766 (genotype p = 0.0048, permutation p = 0.0483) and rs2070673
      (allele: p = 0.0018, permutation p = 0.0199, OR = 1.4528 95%CI = 1.1487-1.8374;
      genotype: p = 0.0020, permutation p = 0.0225). In addition, a GTCAC haplotype
      containing 5 SNPs (rs3813867, rs2031920, rs2031921, rs3813870 and rs2031922) was
      observed to be significantly associated with schizophrenia (p = 7.47E-12,
      permutation p<0.0001). However, no association was found between CYP2E1
      polymorphisms/haplotypes and risperidone response. CONCLUSIONS: Our results
      suggest that CYP2E1 may be a potential risk gene for schizophrenia in the Chinese
      Han population. However, polymorphisms of the CYP2E1 gene may not contribute
      significantly to individual differences in the therapeutic efficacy of
      risperidone. Further studies in larger groups are warranted to confirm our
      results.

PMID- 22606227
TI  - Evidence for the late MMN as a neurophysiological endophenotype for dyslexia.
AB  - Dyslexia affects 5-10% of school-aged children and is therefore one of the most
      common learning disorders. Research on auditory event related potentials (AERP),
      particularly the mismatch negativity (MMN) component, has revealed anomalies in
      individuals with dyslexia to speech stimuli. Furthermore, candidate genes for
      this disorder were found through molecular genetic studies. A current challenge
      for dyslexia research is to understand the interaction between molecular genetics
      and brain function, and to promote the identification of relevant endophenotypes
      for dyslexia. The present study examines MMN, a neurophysiological correlate of
      speech perception, and its potential as an endophenotype for dyslexia in three
      groups of children. The first group of children was clinically diagnosed with
      dyslexia, whereas the second group of children was comprised of their siblings
      who had average reading and spelling skills and were therefore "unaffected"
      despite having a genetic risk for dyslexia. The third group consisted of control
      children who were not related to the other groups and were also unaffected. In
      total, 225 children were included in the study. All children showed clear MMN
      activity to/da/-/ba/contrasts that could be separated into three distinct MMN
      components. Whilst the first two MMN components did not differentiate the groups,
      the late MMN component (300-700 ms) revealed significant group differences. The
      mean area of the late MMN was attenuated in both the dyslexic children and their
      unaffected siblings in comparison to the control children. This finding is
      indicative of analogous alterations of neurophysiological processes in children
      with dyslexia and those with a genetic risk for dyslexia, without a manifestation
      of the disorder. The present results therefore further suggest that the late MMN
      might be a potential endophenotype for dyslexia.

PMID- 22606228
TI  - Reward-related dorsal striatal activity differences between former and current
      cocaine dependent individuals during an interactive competitive game.
AB  - Cocaine addiction is characterized by impulsivity, impaired social relationships,
      and abnormal mesocorticolimbic reward processing, but their interrelationships
      relative to stages of cocaine addiction are unclear. We assessed blood
      oxygenation-level dependent (BOLD) signal in ventral and dorsal striatum during
      functional magnetic resonance imaging (fMRI) in current (CCD; n = 30) and former
      (FCD; n = 28) cocaine dependent subjects as well as healthy control (HC; n = 31)
      subjects while playing an interactive competitive Domino game involving risk
      taking and reward/punishment processing. Out-of-scanner impulsivity-related
      measures were also collected. Although both FCD and CCD subjects scored
      significantly higher on impulsivity-related measures than did HC subjects, only
      FCD subjects had differences in striatal activation, specifically showing
      hypoactivation during their response to gains versus losses in right dorsal
      caudate, a brain region linked to habituation, cocaine craving and addiction
      maintenance. Right caudate activity in FCD subjects also correlated negatively
      with impulsivity-related measures of self-reported compulsivity and sensitivity
      to reward. These findings suggest that remitted cocaine dependence is associated
      with striatal dysfunction during social reward processing in a manner linked to
      compulsivity and reward sensitivity measures. Future research should investigate
      the extent to which such differences might reflect underlying vulnerabilities
      linked to cocaine-using propensities (e.g., relapses).

PMID- 22606229
TI  - Reduced performance of prey targeting in pit vipers with contralaterally occluded
      infrared and visual senses.
AB  - Both visual and infrared (IR) senses are utilized in prey targeting by pit
      vipers. Visual and IR inputs project to the contralateral optic tectum where they
      activate both multimodal and bimodal neurons. A series of ocular and pit organ
      occlusion experiments using the short-tailed pit viper (Gloydius brevicaudus)
      were conducted to investigate the role of visual and IR information during prey
      targeting. Compared with unoccluded controls, snakes with either both eyes or pit
      organs occluded performed more poorly in hunting prey although such subjects
      still captured prey on 75% of trials. Subjects with one eye and one pit occluded
      on the same side of the face performed as well as those with bilateral occlusion
      although these subjects showed a significant targeting angle bias toward the
      unoccluded side. Performance was significantly poorer when only a single eye or
      pit was available. Interestingly, when one eye and one pit organ were occluded on
      opposite sides of the face, performance was poorest, the snakes striking prey on
      no more than half the trials. These results indicate that, visual and infrared
      information are both effective in prey targeting in this species, although
      interference between the two modalities occurs if visual and IR information is
      restricted to opposite sides of the brain.

PMID- 22606230
TI  - Ethanol distribution, dispensing, and use: analysis of a portion of the biomass
      to-biofuels supply chain using system dynamics.
AB  - The Energy Independence and Security Act of 2007 targets use of 36 billion
      gallons of biofuels per year by 2022. Achieving this may require substantial
      changes to current transportation fuel systems for distribution, dispensing, and
      use in vehicles. The U.S. Department of Energy and the National Renewable Energy
      Laboratory designed a system dynamics approach to help focus government action by
      determining what supply chain changes would have the greatest potential to
      accelerate biofuels deployment. The National Renewable Energy Laboratory
      developed the Biomass Scenario Model, a system dynamics model which represents
      the primary system effects and dependencies in the biomass-to-biofuels supply
      chain. The model provides a framework for developing scenarios and conducting
      biofuels policy analysis. This paper focuses on the downstream portion of the
      supply chain-represented in the distribution logistics, dispensing station, and
      fuel utilization, and vehicle modules of the Biomass Scenario Model. This model
      initially focused on ethanol, but has since been expanded to include other
      biofuels. Some portions of this system are represented dynamically with major
      interactions and feedbacks, especially those related to a dispensing station
      owner's decision whether to offer ethanol fuel and a consumer's choice whether to
      purchase that fuel. Other portions of the system are modeled with little or no
      dynamics; the vehicle choices of consumers are represented as discrete scenarios.
      This paper explores conditions needed to sustain an ethanol fuel market and
      identifies implications of these findings for program and policy goals. A large,
      economically sustainable ethanol fuel market (or other biofuel market) requires
      low end-user fuel price relative to gasoline and sufficient producer payment,
      which are difficult to achieve simultaneously. Other requirements (different for
      ethanol vs. other biofuel markets) include the need for infrastructure for
      distribution and dispensing and widespread use of high ethanol blends in flexible
      fuel vehicles.

PMID- 22606231
TI  - Placental expression of CD100, CD72 and CD45 is dysregulated in human
      miscarriage.
AB  - CONTEXT AND OBJECTIVE: The etiology of miscarriage is often multifactorial. One
      major cause, immunological rejection of the fetus, has not been clearly
      elucidated. Our aim was to establish whether the semaphorin CD100, its natural
      receptor CD72, and the glycoprotein CD45, implicated in immune mechanisms, are
      involved in pregnancy loss by examining their placental expression with real-time
      PCR, immunohistochemistry and western blotting techniques. PATIENTS: Placenta
      tissue from 72 Caucasian women undergoing surgical uterine evacuation due to
      early spontaneous pregnancy loss between the 8(th) and 12(th) week of gestation
      was divided into four groups based on miscarriage number. Gestational age-matched
      placentas from 18 healthy women without a history of miscarriage undergoing
      voluntary pregnancy termination were the control group. Placenta from 6 Caesarean
      deliveries performed at 38-40 weeks of gestation was also studied. RESULTS:
      CD100, CD72 and CD45 were expressed in placenta and exhibited different mRNA and
      protein levels in normal pregnancy and miscarriage. In particular, protein levels
      were highly dysregulated around 10 weeks of gestation in first and second
      miscarriage placentas. The CD100 soluble form was produced and immediately shed
      from placental tissue in all samples. CONCLUSIONS: Fetal CD100, CD72 and CD45
      seem to play a role in miscarriage. The present data support the involvement of
      the fetal immune system in pregnancy maintenance as well as failure.

PMID- 22606233
TI  - A new way of identifying biomarkers in biomedical basic-research studies.
AB  - A simple, nonparametric and distribution free method was developed for quick
      identification of the most meaningful biomarkers among a number of candidates in
      complex biological phenomena, especially in relatively small samples. This method
      is independent of rigid model forms or other link functions. It may be applied
      both to metric and non-metric data as well as to independent or matched parallel
      samples. With this method identification of the most relevant biomarkers is not
      based on inferential methods; therefore, its application does not require
      corrections of the level of significance, even in cases of thousands of
      variables. Hence, the introduced method is appropriate to analyze and evaluate
      data of complex investigations in clinical and pre-clinical basic research, such
      as gene or protein expressions, phenotype-genotype associations in case-control
      studies on the basis of thousands of genes and SNPs (single nucleotide
      polymorphism), search of prevalence in sleep EEG-Data, functional magnetic
      resonance imaging (fMRI) or others.

PMID- 22606232
TI  - The effect of ketoconazole on post-burn inflammation, hypermetabolism and
      clinical outcomes.
AB  - BACKGROUND: Hypercortisolemia has been suggested as a primary hormonal mediator
      of whole-body catabolism following severe burn injury. Ketoconazole, an anti
      fungal agent, inhibits cortisol synthesis. We, therefore, studied the effect of
      ketoconazole on post-burn cortisol levels and the hyper-catabolic response in a
      prospective randomized trial (block randomization 2:1). METHODOLOGY/PRINCIPAL
      FINDINGS: Fifty-five severely burned pediatric patients with >30% total body
      surface area (TBSA) burns were enrolled in this trial. Patients were randomized
      to receive standard care plus either placebo (controls, n = 38) or ketoconazole
      (n = 23). Demographics, clinical data, serum hormone levels, serum cytokine
      expression profiles, organ function, hypermetabolism measures, muscle protein
      synthesis, incidence of wound infection sepsis, and body composition were
      obtained throughout the acute hospital course. Statistical analysis was performed
      using Fisher's exact test, Student's t-test, and parametric and non-parametric
      two-way repeated measures analysis of variance where applicable. Patients were
      similar in demographics, age, and TBSA burned. Ketoconazole effectively blocked
      cortisol production, as indicated by normalization of the 8-fold elevation in
      urine cortisol levels [F(1, 376) = 85.34, p<.001] with the initiation of
      treatment. However, there were no significant differences in the inflammatory
      response, acute-phase proteins, body composition, muscle protein breakdown or
      synthesis, or organ function between groups. CONCLUSIONS: Both groups were
      markedly hypermetabolic and catabolic throughout the acute hospital stay.
      Normalization of hypercortisolemia with ketoconazole therapy had no effect on
      whole-body catabolism or the post-burn inflammatory or hypermetabolic response,
      suggesting that hypercortisolemia does not play a central role in the post-burn
      hypermetabolic catabolic response. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00675714; and NCT00673309.

PMID- 22606235
TI  - Viral gastroenteritis associated with genogroup II norovirus among U.S. military
      personnel in Turkey, 2009.
AB  - The present study demonstrates that multiple NoV genotypes belonging to genogroup
      II contributed to an acute gastroenteritis outbreak at a US military facility in
      Turkey that was associated with significant negative operational impact.
      Norovirus (NoV) is an important pathogen associated with acute gastroenteritis
      among military populations. We describe the genotypes of NoV outbreak occurred at
      a United States military facility in Turkey. Stool samples were collected from 37
      out of 97 patients presenting to the clinic on base with acute gastroenteritis
      and evaluated for bacterial and viral pathogens. NoV genogroup II (GII) was
      identified by RT-PCR in 43% (16/37) stool samples. Phylogenetic analysis of a 260
      base pair fragment of the NoV capsid gene from ten stool samples indicated the
      circulation of multiple and rare genotypes of GII NoV during the outbreak. We
      detected four GII.8 isolates, three GII.15, two GII.9 and a sole GII.10 NoV.
      Viral sequences could be grouped into four clusters, three of which have not been
      previously reported in Turkey. The fact that current NoV outbreak was caused by
      rare genotypes highlights the importance of norovirus strain typing. While NoV
      genogroup II is recognized as causative agent of outbreak, circulation of current
      genotypes has been rarely observed in large number of outbreaks.

PMID- 22606234
TI  - Augmented cardiac hypertrophy in response to pressure overload in mice lacking
      ELTD1.
AB  - BACKGROUND: Epidermal growth factor (EGF), latrophilin and seven transmembrane
      domain-containing protein 1 (ELTD1) is developmentally upregulated in the heart.
      Little is known about the relationship between ELTD1 and cardiac diseases.
      Therefore, we aimed to clarify the role of ELTD1 in pressure overload-induced
      cardiac hypertrophy. METHODS AND RESULTS: C57BL/6J wild-type (WT) mice and ELTD1
      knockout (KO) mice were subjected to left ventricular pressure overload by
      descending aortic banding (AB). KO mice exhibited more unfavorable cardiac
      remodeling than WT mice 28 days post AB; this remodeling was characterized by
      aggravated cardiomyocyte hypertrophy, thickening of the ventricular walls,
      dilated chambers, increased fibrosis, and blunted systolic and diastolic cardiac
      function. Analysis of signaling pathways revealed enhanced extracellular signal
      regulated kinase (ERK) and the c-Jun amino-terminal kinase (JNK) phosphorylation
      in response to ELTD1 deletion. CONCLUSIONS: ELTD1 deficiency exacerbates cardiac
      hypertrophy and cardiac function induced by AB-induced pressure overload by
      promoting both cardiomyocyte hypertrophy and cardiac fibrosis. These effects are
      suggested to originate from the activation of the ERK and JNK pathways,
      suggesting that ELTD1 is a potential target for therapies that prevent the
      development of cardiac disease.

PMID- 22606236
TI  - Glucose-dependent regulation of NR2F2 promoter and influence of SNP-rs3743462 on
      whole body insulin sensitivity.
AB  - BACKGROUND: The Nuclear Receptor 2F2 (NR2F2/COUP-TFII) heterozygous knockout mice
      display low basal insulinemia and enhanced insulin sensitivity. We previously
      established that insulin represses NR2F2 gene expression in pancreatic beta
      cells. The cis-regulatory region of the NR2F2 promoter is unknown and its
      influence on metabolism in humans is poorly understood. The present study aimed
      to identify the regulatory regions that control NR2F2 gene transcription and to
      evaluate the effect of NR2F2 promoter variation on glucose homeostasis in humans.
      METHODOLOGY/PRINCIPAL FINDINGS: Regulation of the NR2F2 promoter was assessed
      using gene reporter assays, ChIP and gel shift experiments. The effects of
      variation at SNP rs3743462 in NR2F2 on quantitative metabolic traits were studied
      in two European prospective cohorts. We identified a minimal promoter region that
      down-regulates NR2F2 expression by attenuating HNF4alpha activation in response
      to high glucose concentrations. Subjects of the French DESIR population, who
      carried the rs3743462 T-to-C polymorphism, located in the distal glucose
      responsive promoter, displayed lower basal insulin levels and lower HOMA-IR
      index. The C-allele at rs3743462 was associated with increased NR2F2 binding and
      decreased NR2F2 gene expression. CONCLUSIONS/SIGNIFICANCE: The rs3743462
      polymorphism affects glucose-responsive NR2F2 promoter regulation and thereby may
      influence whole-body insulin sensitivity, suggesting a role of NR2F2 in the
      control of glucose homeostasis in humans.

PMID- 22606237
TI  - Macrophage-specific apoE gene repair reduces diet-induced hyperlipidemia and
      atherosclerosis in hypomorphic Apoe mice.
AB  - BACKGROUND: Apolipoprotein (apo) E is best known for its ability to lower plasma
      cholesterol and protect against atherosclerosis. Although the liver is the major
      source of plasma apoE, extra-hepatic sources of apoE, including from macrophages,
      account for up to 10% of plasma apoE levels. This study examined the contribution
      of macrophage-derived apoE expression levels in diet-induced hyperlipidemia and
      atherosclerosis. METHODOLOGY/PRINCIPAL FINDINGS: Hypomorphic apoE (Apoe(h/h))
      mice expressing wildtype mouse apoE at ~2-5% of physiological levels in all
      tissues were derived by gene targeting in embryonic stem cells. Cre-mediated gene
      repair of the Apoe(h/h) allele in Apoe(h/h)LysM-Cre mice raised apoE expression
      levels by 26 fold in freshly isolated peritoneal macrophages, restoring it to 37%
      of levels seen in wildtype mice. Chow-fed Apoe(h/h)LysM-Cre and Apoe(h/h) mice
      displayed similar plasma apoE and cholesterol levels (55.53+/-2.90 mg/dl versus
      62.70+/-2.77 mg/dl, n = 12). When fed a high-cholesterol diet (HCD) for 16 weeks,
      Apoe(h/h)LysM-Cre mice displayed a 3-fold increase in plasma apoE and a
      concomitant 32% decrease in plasma cholesterol when compared to Apoe(h/h) mice
      (602.20+/-22.30 mg/dl versus 888.80+/-24.99 mg/dl, n = 7). On HCD, Apoe(h/h)LysM
      Cre mice showed increased apoE immunoreactivity in lesional macrophages and liver
      associated Kupffer cells but not hepatocytes. In addition, Apoe(h/h)LysM-Cre mice
      developed 35% less atherosclerotic lesions in the aortic root than Apoe(h/h) mice
      (167*10(3)+/-16*10(3) um(2) versus 259*10(3)+/-56*10(3) um(2), n = 7). This
      difference in atherosclerosis lesions size was proportional to the observed
      reduction in plasma cholesterol. CONCLUSIONS/SIGNIFICANCE: Macrophage-derived
      apoE raises plasma apoE levels in response to diet-induced hyperlipidemia and by
      such reduces atherosclerosis proportionally to the extent to which it lowers
      plasma cholesterol levels.

PMID- 22606238
TI  - Redox proteomics identification of oxidatively modified myocardial proteins in
      human heart failure: implications for protein function.
AB  - Increased oxidative stress in a failing heart may contribute to the pathogenesis
      of heart failure (HF). The aim of this study was to identify the oxidised
      proteins in the myocardium of HF patients and analyse the consequences of
      oxidation on protein function. The carbonylated proteins in left ventricular
      tissue from failing (n = 14) and non-failing human hearts (n = 13) were measured
      by immunoassay and identified by proteomics. HL-1 cardiomyocytes were incubated
      in the presence of stimuli relevant for HF in order to assess the generation of
      reactive oxygen species (ROS), the induction of protein carbonylation, and its
      consequences on protein function. The levels of carbonylated proteins were
      significantly higher in the HF patients than in the controls (p<0.01). We
      identified two proteins that mainly underwent carbonylation: M-type creatine
      kinase (M-CK), whose activity is impaired, and, to a lesser extent, alpha-cardiac
      actin. Exposure of cardiomyocytes to angiotensin II and norepinephrine led to ROS
      generation and M-CK carbonylation with loss of its enzymatic activity. Our
      findings indicate that protein carbonylation is increased in the myocardium
      during HF and that these oxidative changes may help to explain the decreased CK
      activity and consequent defects in energy metabolism observed in HF.

PMID- 22606239
TI  - Research blogs and the discussion of scholarly information.
AB  - The research blog has become a popular mechanism for the quick discussion of
      scholarly information. However, unlike peer-reviewed journals, the
      characteristics of this form of scientific discourse are not well understood, for
      example in terms of the spread of blogger levels of education, gender and
      institutional affiliations. In this paper we fill this gap by analyzing a sample
      of blog posts discussing science via an aggregator called ResearchBlogging.org
      (RB). ResearchBlogging.org aggregates posts based on peer-reviewed research and
      allows bloggers to cite their sources in a scholarly manner. We studied the
      bloggers, blog posts and referenced journals of bloggers who posted at least 20
      items. We found that RB bloggers show a preference for papers from high-impact
      journals and blog mostly about research in the life and behavioral sciences. The
      most frequently referenced journal sources in the sample were: Science, Nature,
      PNAS and PLoS One. Most of the bloggers in our sample had active Twitter accounts
      connected with their blogs, and at least 90% of these accounts connect to at
      least one other RB-related Twitter account. The average RB blogger in our sample
      is male, either a graduate student or has been awarded a PhD and blogs under his
      own name.

PMID- 22606240
TI  - Complete chloroplast genome sequences of important oilseed crop Sesamum indicum
      L.
AB  - Sesamum indicum is an important crop plant species for yielding oil. The complete
      chloroplast (cp) genome of S. indicum (GenBank acc no. JN637766) is 153,324 bp in
      length, and has a pair of inverted repeat (IR) regions consisting of 25,141 bp
      each. The lengths of the large single copy (LSC) and the small single copy (SSC)
      regions are 85,170 bp and 17,872 bp, respectively. Comparative cp DNA sequence
      analyses of S. indicum with other cp genomes reveal that the genome structure,
      gene order, gene and intron contents, AT contents, codon usage, and transcription
      units are similar to the typical angiosperm cp genomes. Nucleotide diversity of
      the IR region between Sesamum and three other cp genomes is much lower than that
      of the LSC and SSC regions in both the coding region and noncoding region. As a
      summary, the regional constraints strongly affect the sequence evolution of the
      cp genomes, while the functional constraints weakly affect the sequence evolution
      of cp genomes. Five short inversions associated with short palindromic sequences
      that form step-loop structures were observed in the chloroplast genome of S.
      indicum. Twenty-eight different simple sequence repeat loci have been detected in
      the chloroplast genome of S. indicum. Almost all of the SSR loci were composed of
      A or T, so this may also contribute to the A-T richness of the cp genome of S.
      indicum. Seven large repeated loci in the chloroplast genome of S. indicum were
      also identified and these loci are useful to developing S. indicum-specific cp
      genome vectors. The complete cp DNA sequences of S. indicum reported in this
      paper are prerequisite to modifying this important oilseed crop by cp genetic
      engineering techniques.

PMID- 22606241
TI  - Prevalence of JC virus in Chinese patients with colorectal cancer.
AB  - BACKGROUND: JCV is a DNA polyomavirus very well adapted to humans. Although JCV
      DNA has been detected in colorectal cancers (CRC), the association between JCV
      and CRC remains controversial. In China, the presence of JCV infection in CRC
      patients has not been reported. Here, we investigated JCV infection and viral DNA
      load in Chinese CRC patients and to determine whether the JCV DNA in peripheral
      blood (PB) can be used as a diagnostic marker for JCV-related CRC.
      METHODOLOGY/PRINCIPAL FINDINGS: Tumor tissues, non-cancerous tumor-adjacent
      tissues and PB samples were collected from 137 CRC patients. In addition, 80
      normal colorectal tissue samples from patients without CRC and PB samples from
      100 healthy volunteers were also harvested as controls. JCV DNA was detected by
      nested PCR and glass slide-based dot blotting. Viral DNA load of positive samples
      were determined by quantitative real-time PCR. JCV DNA was detected in 40.9%
      (56/137) of CRC tissues at a viral load of 49.1 to 10.3*10(4) copies/ug DNA.
      Thirty-four (24.5%) non-cancerous colorectal tissues (192.9 to 4.4*10(3)
      copies/ug DNA) and 25 (18.2%) PB samples (81.3 to 4.9*10(3) copies/ug DNA) from
      CRC patients were positive for JCV. Tumor tissues had higher levels of JCV than
      non-cancerous tissues (P = 0.003) or PB samples (P<0.001). No correlation between
      the presence of JCV and demographic or medical characteristics was observed. The
      JCV prevalence in PB samples was significantly associated with the JCV status in
      tissue samples (P<0.001). Eleven (13.8%) normal colorectal tissues and seven
      (7.0%) PB samples from healthy donors were positive for JCV.
      CONCLUSIONS/SIGNIFICANCE: JCV infection is frequently present in colorectal tumor
      tissues of CRC patients. Although the association between JCV presence in PB
      samples and JCV status in tissue samples was identified in this study, whether PB
      JCV detection can serve as a marker for JCV status of CRC requires further study.

PMID- 22606242
TI  - Resistance of Trichoplusia ni to Bacillus thuringiensis toxin Cry1Ac is
      independent of alteration of the cadherin-like receptor for Cry toxins.
AB  - Alteration of binding sites for Bacillus thuringiensis (Bt) toxins in insect
      midgut is the major mechanism of high-level resistance to Bt toxins in insects.
      The midgut cadherin is known to be a major binding protein for Bt Cry1A toxins
      and linkage of Bt-resistance to cadherin gene mutations has been identified in
      lepidopterans. The resistance to Bt toxin Cry1Ac evolved in greenhouse
      populations of Trichoplusia ni has been identified to be associated with the down
      regulation of an aminopeptidase N (APN1) gene by a trans-regulatory mechanism and
      the resistance gene has been mapped to the locus of an ABC transporter (ABCC2)
      gene. However, whether cadherin is also involved with Cry1Ac-resistance in T. ni
      requires to be understood. Here we report that the Cry1Ac-resistance in T. ni is
      independent of alteration of the cadherin. The T. ni cadherin cDNA was cloned and
      the cadherin sequence showed characteristic features known to cadherins from
      Lepidoptera. Various T. ni cadherin gene alleles were identified and genetic
      linkage analysis of the cadherin alleles with Cry1Ac-resistance showed no
      association of the cadherin gene with the Cry1Ac-resistance in T. ni. Analysis of
      cadherin transcripts showed no quantitative difference between the susceptible
      and Cry1Ac-resistant T. ni larvae. Quantitative proteomic analysis of midgut BBMV
      proteins by iTRAQ-2D-LC-MS/MS determined that there was no quantitative
      difference in cadherin content between the susceptible and the resistant larvae
      and the cadherin only accounted for 0.0014% (mol%) of the midgut BBMV proteins,
      which is 1/300 of APN1 in molar ratio. The cadherin from both the susceptible and
      resistant larvae showed as a 200-kDa Cry1Ac-binding protein by toxin overlay
      binding analysis, and nano-LC-MS/MS analysis of the 200-kDa cadherin determined
      that there is no quantitative difference between the susceptible and resistant
      larvae. Results from this study indicate that the Cry1Ac-resistance in T. ni is
      independent of cadherin alteration.

PMID- 22606243
TI  - Identification of the rostral migratory stream in the canine and feline brain.
AB  - In the adult rodent brain, neural progenitor cells migrate from the
      subventricular zone of the lateral ventricle towards the olfactory bulb in a
      track known as the rostral migratory stream (RMS). To facilitate the study of
      neural progenitor cells and stem cell therapy in large animal models of CNS
      disease, we now report the location and characteristics of the normal canine and
      feline RMS. The RMS was found in Nissl-stained sagittal sections of adult canine
      and feline brains as a prominent, dense, continuous cellular track beginning at
      the base of the anterior horn of the lateral ventricle, curving around the head
      of the caudate nucleus and continuing laterally and ventrally to the olfactory
      peduncle before entering the olfactory tract and bulb. To determine if cells in
      the RMS were proliferating, the thymidine analog 5-bromo-2-deoxyuridine (BrdU)
      was administered and detected by immunostaining. BrdU-immunoreactive cells were
      present throughout this track. The RMS was also immunoreactive for markers of
      proliferating cells, progenitor cells and immature neurons (Ki-67 and
      doublecortin), but not for NeuN, a marker of mature neurons. Luxol fast blue and
      CNPase staining indicated that myelin is closely apposed to the RMS along much of
      its length and may provide guidance cues for the migrating cells. Identification
      and characterization of the RMS in canine and feline brain will facilitate
      studies of neural progenitor cell biology and migration in large animal models of
      neurologic disease.

PMID- 22606244
TI  - Suppression of ribosomal function triggers innate immune signaling through
      activation of the NLRP3 inflammasome.
AB  - Some inflammatory stimuli trigger activation of the NLRP3 inflammasome by
      inducing efflux of cellular potassium. Loss of cellular potassium is known to
      potently suppress protein synthesis, leading us to test whether the inhibition of
      protein synthesis itself serves as an activating signal for the NLRP3
      inflammasome. Murine bone marrow-derived macrophages, either primed by LPS or
      unprimed, were exposed to a panel of inhibitors of ribosomal function: ricin,
      cycloheximide, puromycin, pactamycin, and anisomycin. Macrophages were also
      exposed to nigericin, ATP, monosodium urate (MSU), and poly I:C. Synthesis of pro
      IL-beta and release of IL-1beta from cells in response to these agents was
      detected by immunoblotting and ELISA. Release of intracellular potassium was
      measured by mass spectrometry. Inhibition of translation by each of the tested
      translation inhibitors led to processing of IL-1beta, which was released from
      cells. Processing and release of IL-1beta was reduced or absent from cells
      deficient in NLRP3, ASC, or caspase-1, demonstrating the role of the NLRP3
      inflammasome. Despite the inability of these inhibitors to trigger efflux of
      intracellular potassium, the addition of high extracellular potassium suppressed
      activation of the NLRP3 inflammasome. MSU and double-stranded RNA, which are
      known to activate the NLRP3 inflammasome, also substantially inhibited protein
      translation, supporting a close association between inhibition of translation and
      inflammasome activation. These data demonstrate that translational inhibition
      itself constitutes a heretofore-unrecognized mechanism underlying IL-1beta
      dependent inflammatory signaling and that other physical, chemical, or pathogen
      associated agents that impair translation may lead to IL-1beta-dependent
      inflammation through activation of the NLRP3 inflammasome. For agents that
      inhibit translation through decreased cellular potassium, the application of high
      extracellular potassium restores protein translation and suppresses activation of
      the NLRP inflammasome. For agents that inhibit translation through mechanisms
      that do not involve loss of potassium, high extracellular potassium suppresses IL
      1beta processing through a mechanism that remains undefined.

PMID- 22606245
TI  - Evolutionary dynamics of co-segregating gene clusters associated with complex
      diseases.
AB  - BACKGROUND: The distribution of human disease-associated mutations is not random
      across the human genome. Despite the fact that natural selection continually
      removes disease-associated mutations, an enrichment of these variants can be
      observed in regions of low recombination. There are a number of mechanisms by
      which such a clustering could occur, including genetic perturbations or
      demographic effects within different populations. Recent genome-wide association
      studies (GWAS) suggest that single nucleotide polymorphisms (SNPs) associated
      with complex disease traits are not randomly distributed throughout the genome,
      but tend to cluster in regions of low recombination. PRINCIPAL FINDINGS: Here we
      investigated whether deleterious mutations have accumulated in regions of low
      recombination due to the impact of recent positive selection and genetic
      hitchhiking. Using publicly available data on common complex diseases and
      population demography, we observed an enrichment of hitchhiked disease
      associations in conserved gene clusters subject to selection pressure.
      Evolutionary analysis revealed that these conserved gene clusters arose by
      multiple concerted rearrangements events across the vertebrate lineage. We
      observed distinct clustering of disease-associated SNPs in evolutionary
      rearranged regions of low recombination and high gene density, which harbor genes
      involved in immunity, that is, the interleukin cluster on 5q31 or RhoA on 3p21.
      CONCLUSIONS: Our results suggest that multiple lineage specific rearrangements
      led to a physical clustering of functionally related and linked genes exhibiting
      an enrichment of susceptibility loci for complex traits. This implies that
      besides recent evolutionary adaptations other evolutionary dynamics have played a
      role in the formation of linked gene clusters associated with complex disease
      traits.

PMID- 22606246
TI  - Bmi1 confers resistance to oxidative stress on hematopoietic stem cells.
AB  - BACKGROUND: The polycomb-group (PcG) proteins function as general regulators of
      stem cells. We previously reported that retrovirus-mediated overexpression of
      Bmi1, a gene encoding a core component of polycomb repressive complex (PRC) 1,
      maintained self-renewing hematopoietic stem cells (HSCs) during long-term
      culture. However, the effects of overexpression of Bmi1 on HSCs in vivo remained
      to be precisely addressed. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we
      generated a mouse line where Bmi1 can be conditionally overexpressed under the
      control of the endogenous Rosa26 promoter in a hematopoietic cell-specific
      fashion (Tie2-Cre;R26Stop(FL)Bmi1). Although overexpression of Bmi1 did not
      significantly affect steady state hematopoiesis, it promoted expansion of
      functional HSCs during ex vivo culture and efficiently protected HSCs against
      loss of self-renewal capacity during serial transplantation. Overexpression of
      Bmi1 had no effect on DNA damage response triggered by ionizing radiation. In
      contrast, Tie2-Cre;R26Stop(FL)Bmi1 HSCs under oxidative stress maintained a
      multipotent state and generally tolerated oxidative stress better than the
      control. Unexpectedly, overexpression of Bmi1 had no impact on the level of
      intracellular reactive oxygen species (ROS). CONCLUSIONS/SIGNIFICANCE: Our
      findings demonstrate that overexpression of Bmi1 confers resistance to stresses,
      particularly oxidative stress, onto HSCs. This thereby enhances their
      regenerative capacity and suggests that Bmi1 is located downstream of ROS
      signaling and negatively regulated by it.

PMID- 22606247
TI  - Permissible variation in the 3' non-coding region of the haemagglutinin genome
      segment of the H5N1 candidate influenza vaccine virus NIBRG-14 [corrected].
AB  - The candidate H5N1 vaccine virus NIBRG-14 was created in response to a call from
      the World Health Organisation in 2004 to prepare candidate vaccine viruses (CVVs)
      to combat the threat of an H5N1 pandemic. NIBRG-14 was created by reverse
      genetics and is composed of the neuraminidase (NA) and modified haemagglutinin
      (HA) genes from A/Vietnam/1194/2004 and the internal genes of PR8, a high growing
      laboratory adapted influenza A(H1N1) strain. Due to time constraints, the non
      coding regions (NCRs) of A/Vietnam/1194/2004 HA were not determined prior to
      creating NIBRG-14. Consequently, the sequence of the primers used to clone the
      modified A/Vietnam/1194/2004 HA was based upon previous experience of cloning
      H5N1 viruses. We report here that the HA 3' NCR sequence of NIBRG-14 is different
      to that of the parental wild type virus A/Vietnam/1194/2004; however this does
      not appear to impact on its growth or antigen yield. We introduced additional
      small changes into the 3'NCR of NIBRG-14; these had only minor effects on viral
      growth and antigen content. These findings may serve to assure the influenza
      vaccine community that generation of CVVs using best-guess NCR sequences, based
      on sequence alignments, are likely to produce robust viruses.

PMID- 22606248
TI  - The genetic structure of Leishmania infantum populations in Brazil and its
      possible association with the transmission cycle of visceral leishmaniasis.
AB  - Leishmania infantum is the etiologic agent of visceral leishmaniasis (VL) in the
      Americas, Mediterranean basin and West and Central Asia. Although the geographic
      structure of L. infantum populations from the Old World have been described, few
      studies have addressed the population structure of this parasite in the
      Neotropical region. We employed 14 microsatellites to analyze the population
      structure of the L. infantum strains isolated from humans and dogs from most of
      the Brazilian states endemic for VL and from Paraguay. The results indicate a low
      genetic diversity, high inbreeding estimates and a depletion of heterozygotes,
      which together indicate a predominantly clonal breeding system, but signs of
      sexual events are also present. Three populations were identified from the
      clustering analysis, and they were well supported by F statistics inferences and
      partially corroborated by distance-based. POP1 (111 strains) was observed in all
      but one endemic area. POP2 (31 strains) is also well-dispersed, but it was the
      predominant population in Mato Grosso (MT). POP3 (31 strains) was less dispersed,
      and it was observed primarily in Mato Grosso do Sul (MS). Strains originated from
      an outbreak of canine VL in Southern Brazil were grouped in POP1 with those from
      Paraguay, which corroborates the hypothesis of dispersal from Northeastern
      Argentina and Paraguay. The distribution of VL in MS seems to follow the west
      east construction of the Bolivia-Brazil pipeline from Corumba municipality. This
      may have resulted in a strong association of POP3 and Lutzomyia cruzi, which is
      the main VL vector in Corumba, and a dispersion of this population in this region
      that was shaped by human interference. This vector also occurs in MT and may
      influence the structure of POP2. This paper presents significant advances in the
      understanding of the population structure of L. infantum in Brazil and its
      association with eco-epidemiological aspects of VL.

PMID- 22606249
TI  - Microbiota/host crosstalk biomarkers: regulatory response of human intestinal
      dendritic cells exposed to Lactobacillus extracellular encrypted peptide.
AB  - The human gastrointestinal tract is exposed to a huge variety of microorganisms,
      either commensal or pathogenic; at this site, a balance between immunity and
      immune tolerance is required. Intestinal dendritic cells (DCs) control the
      mechanisms of immune response/tolerance in the gut. In this paper we have
      identified a peptide (STp) secreted by Lactobacillus plantarum, characterized by
      the abundance of serine and threonine residues within its sequence. STp is
      encoded in one of the main extracellular proteins produced by such species, which
      includes some probiotic strains, and lacks cleavage sites for the major
      intestinal proteases. When studied in vitro, STp expanded the ongoing production
      of regulatory IL-10 in human intestinal DCs from healthy controls. STp-primed DC
      induced an immunoregulatory cytokine profile and skin-homing profile on
      stimulated T-cells. Our data suggest that some of the molecular dialogue between
      intestinal bacteria and DCs may be mediated by immunomodulatory peptides, encoded
      in larger extracellular proteins, secreted by commensal bacteria. These peptides
      may be used for the development of nutraceutical products for patients with IBD.
      In addition, this kind of peptides seem to be absent in the gut of inflammatory
      bowel disease patients, suggesting a potential role as biomarker of gut
      homeostasis.

PMID- 22606250
TI  - Comparable ages for the independent origins of electrogenesis in African and
      South American weakly electric fishes.
AB  - One of the most remarkable examples of convergent evolution among vertebrates is
      illustrated by the independent origins of an active electric sense in South
      American and African weakly electric fishes, the Gymnotiformes and Mormyroidea,
      respectively. These groups independently evolved similar complex systems for
      object localization and communication via the generation and reception of weak
      electric fields. While good estimates of divergence times are critical to
      understanding the temporal context for the evolution and diversification of these
      two groups, their respective ages have been difficult to estimate due to the
      absence of an informative fossil record, use of strict molecular clock models in
      previous studies, and/or incomplete taxonomic sampling. Here, we examine the
      timing of the origins of the Gymnotiformes and the Mormyroidea using complete
      mitogenome sequences and a parametric bayesian method for divergence time
      reconstruction. Under two different fossil-based calibration methods, we
      estimated similar ages for the independent origins of the Mormyroidea and
      Gymnotiformes. Our absolute estimates for the origins of these groups either
      slightly postdate, or just predate, the final separation of Africa and South
      America by continental drift. The most recent common ancestor of the Mormyroidea
      and Gymnotiformes was found to be a non-electrogenic basal teleost living more
      than 85 millions years earlier. For both electric fish lineages, we also
      estimated similar intervals (16-19 or 22-26 million years, depending on
      calibration method) between the appearance of electroreception and the origin of
      myogenic electric organs, providing rough upper estimates for the time periods
      during which these complex electric organs evolved de novo from skeletal muscle
      precursors. The fact that the Gymnotiformes and Mormyroidea are of similar age
      enhances the comparative value of the weakly electric fish system for
      investigating pathways to evolutionary novelty, as well as the influences of key
      innovations in communication on the process of species radiation.

PMID- 22606251
TI  - Bacterial communities of the coronal sulcus and distal urethra of adolescent
      males.
AB  - Lactobacillus-dominated vaginal microbiotas are associated with reproductive
      health and STI resistance in women, whereas altered microbiotas are associated
      with bacterial vaginosis (BV), STI risk and poor reproductive outcomes. Putative
      vaginal taxa have been observed in male first-catch urine, urethral swab and
      coronal sulcus (CS) specimens but the significance of these observations is
      unclear. We used 16 S rRNA sequencing to characterize the microbiota of the CS
      and urine collected from 18 adolescent men over three consecutive months. CS
      microbiotas of most participants were more stable than their urine microbiotas
      and the composition of CS microbiotas were strongly influenced by circumcision.
      BV-associated taxa, including Atopobium, Megasphaera, Mobiluncus, Prevotella and
      Gemella, were detected in CS specimens from sexually experienced and
      inexperienced participants. In contrast, urine primarily contained taxa that were
      not abundant in CS specimens. Lactobacilllus and Streptococcus were major urine
      taxa but their abundance was inversely correlated. In contrast, Sneathia,
      Mycoplasma and Ureaplasma were only found in urine from sexually active
      participants. Thus, the CS and urine support stable and distinct bacterial
      communities. Finally, our results suggest that the penis and the urethra can be
      colonized by a variety of BV-associated taxa and that some of these colonizations
      result from partnered sexual activity.

PMID- 22606252
TI  - Prevalence of psychological trauma and association with current health and
      functioning in a sample of HIV-infected and HIV-uninfected Tanzanian adults.
AB  - BACKGROUND: In high income nations, traumatic life experiences such as childhood
      sexual abuse are much more common in people living with HIV/AIDS (PLWHA) than the
      general population, and trauma is associated with worse current health and
      functioning. Virtually no data exist on the prevalence or consequences of trauma
      for PLWHA in low income nations. METHODOLOGY/PRINCIPAL FINDINGS: We recruited
      four cohorts of Tanzanian patients in established medical care for HIV infection
      (n = 228), individuals newly testing positive for HIV (n = 267), individuals
      testing negative for HIV at the same sites (n = 182), and a random sample of
      community-dwelling adults (n = 249). We assessed lifetime prevalence of traumatic
      experiences, recent stressful life events, and current mental health and health
      related physical functioning. Those with established HIV infection reported a
      greater number of childhood and lifetime traumatic experiences (2.1 and 3.0
      respectively) than the community cohort (1.8 and 2.3). Those with established HIV
      infection reported greater post-traumatic stress disorder (PTSD) symptomatology
      and worse current health-related physical functioning. Each additional lifetime
      traumatic experience was associated with increased PTSD symptomatology and worse
      functioning. CONCLUSIONS/SIGNIFICANCE: This study is the first to our knowledge
      in an HIV population from a low income nation to report the prevalence of a range
      of potentially traumatic life experiences compared to a matched community sample
      and to show that trauma history is associated with poorer health-related physical
      functioning. Our findings underscore the importance of considering psychosocial
      characteristics when planning to meet the health needs of PLWHA in low income
      countries.

PMID- 22606253
TI  - rs4919510 in hsa-mir-608 is associated with outcome but not risk of colorectal
      cancer.
AB  - BACKGROUND: Colorectal cancer is the third most incident cancer and cause of
      cancer-related death in the United States. MicroRNAs, a class of small non-coding
      RNAs, have been implicated in the pathogenesis and prognosis of colorectal
      cancer, although few studies have examined the relationship between germline
      mutation in the microRNAs with risk and prognosis. We therefore investigated the
      association between a SNP in hsa-mir-608, which lies within the 10q24 locus, and
      colorectal cancer. METHODS AND RESULTS: A cohort consisting of 245 cases and 446
      controls was genotyped for rs4919510. The frequency of the GG genotype was
      significantly higher in African Americans (15%) compared to Caucasians (3%)
      controls. There was no significant association between rs4919510 and colorectal
      cancer risk (African American: OR(GG vs. CC) 0.89 [95% CI, 0.41-1.80])
      (Caucasian: OR(GG vs. CC) 1.76, ([95% CI, 0.48-6.39]). However, we did observe an
      association with survival. The GG genotype was associated with an increased risk
      of death in Caucasians (HR(GG vs. CC) 3.54 ([95% CI, 1.38-9.12]) and with a
      reduced risk of death in African Americans (HR(GG vs. CC) 0.36 ([95% CI 0.12
      1.07). CONCLUSIONS: These results suggest that rs4910510 may be associated with
      colorectal cancer survival in a manner that is dependent on race.

PMID- 22606254
TI  - A linear framework for time-scale separation in nonlinear biochemical systems.
AB  - Cellular physiology is implemented by formidably complex biochemical systems with
      highly nonlinear dynamics, presenting a challenge for both experiment and theory.
      Time-scale separation has been one of the few theoretical methods for distilling
      general principles from such complexity. It has provided essential insights in
      areas such as enzyme kinetics, allosteric enzymes, G-protein coupled receptors,
      ion channels, gene regulation and post-translational modification. In each case,
      internal molecular complexity has been eliminated, leading to rational algebraic
      expressions among the remaining components. This has yielded familiar formulas
      such as those of Michaelis-Menten in enzyme kinetics, Monod-Wyman-Changeux in
      allostery and Ackers-Johnson-Shea in gene regulation. Here we show that these
      calculations are all instances of a single graph-theoretic framework. Despite the
      biochemical nonlinearity to which it is applied, this framework is entirely
      linear, yet requires no approximation. We show that elimination of internal
      complexity is feasible when the relevant graph is strongly connected. The
      framework provides a new methodology with the potential to subdue combinatorial
      explosion at the molecular level.

PMID- 22606255
TI  - A comparison of three methods to measure asthma in epidemiologic studies: results
      from the Danish National Birth Cohort.
AB  - Asthma is a heterogeneous outcome and how the condition should be measured to
      best capture clinically relevant disease in epidemiologic studies remains
      unclear. We compared three methods of measuring asthma in the Danish National
      Birth Cohort (n>50.000). When the children were 7 years old, the prevalence of
      asthma was estimated from a self-administered questionnaire using parental report
      of doctor diagnoses, ICD-10 diagnoses from a population-based hospitalization
      registry, and data on anti-asthmatic medication from a population-based
      prescription registry. We assessed the agreement between the methods using kappa
      statistics. Highest prevalence of asthma was found using the prescription
      registry (32.2%) followed by the self-report (12.0%) and the hospitalization
      registry (6.6%). We found a substantial non-overlap between the methods (kappa =
      0.21-0.38). When all three methods were combined the asthma prevalence was 3.6%.
      In conclusion, self-reported asthma, ICD-10 diagnoses from a hospitalization
      registry and data on anti-asthmatic medication use from a prescription registry
      lead to different prevalences of asthma in the same cohort of children. The non
      overlap between the methods may be due to different abilities of the methods to
      identify cases with different phenotypes, in which case they should be treated as
      separate outcomes in future aetiological studies.

PMID- 22606257
TI  - Haploinsufficiency of the E3 ubiquitin ligase C-terminus of heat shock cognate 70
      interacting protein (CHIP) produces specific behavioral impairments.
AB  - The multifunctional E3 ubiquitin ligase CHIP is an essential interacting partner
      of HSP70, which together promote the proteasomal degradation of client proteins.
      Acute CHIP overexpression provides neuroprotection against neurotoxic
      mitochondrial stress, glucocorticoids, and accumulation of toxic amyloid
      fragments, as well as genetic mutations in other E3 ligases, which have been
      shown to result in familial Parkinson's disease. These studies have created a
      great deal of interest in understanding CHIP activity, expression and modulation.
      While CHIP knockout mice have the potential to provide essential insights into
      the molecular control of cell fate and survival, the animals have been difficult
      to characterize in vivo due to severe phenotypic and behavioral dysfunction,
      which have thus far been poorly characterized. Therefore, in the present study we
      conducted a battery of neurobehavioral and physiological assays of adult CHIP
      heterozygotic (HET) mutant mice to provide a better understanding of the
      functional consequence of CHIP deficiency. We found that CHIP HET mice had normal
      body and brain weight, body temperature, muscle tone and breathing patterns, but
      do have a significant elevation in baseline heart rate. Meanwhile basic
      behavioral screens of sensory, motor, emotional and cognitive functions were
      normative. We observed no alterations in performance in the elevated plus maze,
      light-dark preference and tail suspension assays, or two simple cognitive tasks:
      novel object recognition and spontaneous alternation in a Y maze. Significant
      deficits were found, however, when CHIP HET mice performed wire hang, inverted
      screen, wire maneuver, and open field tasks. Taken together, our data indicate a
      clear subset of behaviors that are altered at baseline in CHIP deficient animals,
      which will further guide whole animal studies of the effects of CHIP
      dysregulation on cardiac function, brain circuitry and function, and
      responsiveness to environmental and cellular stress.

PMID- 22606258
TI  - N-player quantum games in an EPR setting.
AB  - The N-player quantum games are analyzed that use an Einstein-Podolsky-Rosen (EPR)
      experiment, as the underlying physical setup. In this setup, a player's
      strategies are not unitary transformations as in alternate quantum game-theoretic
      frameworks, but a classical choice between two directions along which spin or
      polarization measurements are made. The players' strategies thus remain identical
      to their strategies in the mixed-strategy version of the classical game. In the
      EPR setting the quantum game reduces itself to the corresponding classical game
      when the shared quantum state reaches zero entanglement. We find the relations
      for the probability distribution for N-qubit GHZ and W-type states, subject to
      general measurement directions, from which the expressions for the players'
      payoffs and mixed Nash equilibrium are determined. Players' N x N payoff matrices
      are then defined using linear functions so that common two-player games can be
      easily extended to the N-player case and permit analytic expressions for the Nash
      equilibrium. As a specific example, we solve the Prisoners' Dilemma game for
      general N >= 2. We find a new property for the game that for an even number of
      players the payoffs at the Nash equilibrium are equal, whereas for an odd number
      of players the cooperating players receive higher payoffs. By dispensing with the
      standard unitary transformations on state vectors in Hilbert space and using
      instead rotors and multivectors, based on Clifford's geometric algebra (GA), it
      is shown how the N-player case becomes tractable. The new mathematical approach
      presented here has wide implications in the areas of quantum information and
      quantum complexity, as it opens up a powerful way to tractably analyze N-partite
      qubit interactions.

PMID- 22606256
TI  - How linear tension converts to curvature: geometric control of bone tissue
      growth.
AB  - This study investigated how substrate geometry influences in-vitro tissue
      formation at length scales much larger than a single cell. Two-millimetre thick
      hydroxyapatite plates containing circular pores and semi-circular channels of 0.5
      mm radius, mimicking osteons and hemi-osteons respectively, were incubated with
      MC3T3-E1 cells for 4 weeks. The amount and shape of the tissue formed in the
      pores, as measured using phase contrast microscopy, depended on the substrate
      geometry. It was further demonstrated, using a simple geometric model, that the
      observed curvature-controlled growth can be derived from the assembly of tensile
      elements on a curved substrate. These tensile elements are cells anchored on
      distant points of the curved surface, thus creating an actin "chord" by
      generating tension between the adhesion sites. Such a chord model was used to
      link the shape of the substrate to cell organisation and tissue patterning. In a
      pore with a circular cross-section, tissue growth increases the average curvature
      of the surface, whereas a semi-circular channel tends to be flattened out.
      Thereby, a single mechanism could describe new tissue growth in both cortical and
      trabecular bone after resorption due to remodelling. These similarities between
      in-vitro and in-vivo patterns suggest geometry as an important signal for bone
      remodelling.

PMID- 22606259
TI  - Statistical predictions for the dynamics of a low-speed system: Newtonian versus
      special-relativistic mechanics.
AB  - The newtonian and special-relativistic statistical predictions for the mean,
      standard deviation and probability density function of the position and momentum
      are compared for the periodically-delta-kicked particle at low speed. Contrary to
      expectation, we find that the statistical predictions, which are calculated from
      the same parameters and initial gaussian ensemble of trajectories, do not always
      agree if the initial ensemble is sufficiently well-localized in phase space.
      Moreover, the breakdown of agreement is very fast if the trajectories in the
      ensemble are chaotic, but very slow if the trajectories in the ensemble are non
      chaotic. The breakdown of agreement implies that special-relativistic mechanics
      must be used, instead of the standard practice of using newtonian mechanics, to
      correctly calculate the statistical predictions for the dynamics of a low-speed
      system.

PMID- 22606261
TI  - Using goal- and grip-related information for understanding the correctness of
      other's actions: an ERP study.
AB  - Detecting errors in other's actions is of pivotal importance for joint action,
      competitive behavior and observational learning. Although many studies have
      focused on the neural mechanisms involved in detecting low-level errors,
      relatively little is known about error-detection in everyday situations. The
      present study aimed to identify the functional and neural mechanisms whereby we
      understand the correctness of other's actions involving well-known objects (e.g.
      pouring coffee in a cup). Participants observed action sequences in which the
      correctness of the object grasped and the grip applied to a pair of objects were
      independently manipulated. Observation of object violations (e.g. grasping the
      empty cup instead of the coffee pot) resulted in a stronger P3-effect than
      observation of grip errors (e.g. grasping the coffee pot at the upper part
      instead of the handle), likely reflecting a reorienting response, directing
      attention to the relevant location. Following the P3-effect, a parietal slow wave
      positivity was observed that persisted for grip-errors, likely reflecting the
      detection of an incorrect hand-object interaction. These findings provide new
      insight in the functional significance of the neurophysiological markers
      associated with the observation of incorrect actions and suggest that the P3
      effect and the subsequent parietal slow wave positivity may reflect the detection
      of errors at different levels in the action hierarchy. Thereby this study
      elucidates the cognitive processes that support the detection of action
      violations in the selection of objects and grips.

PMID- 22606260
TI  - Prolactin receptor in primary hyperparathyroidism--expression, functionality and
      clinical correlations.
AB  - BACKGROUND: Primary hyperparathyroidism (PHPT) is an endocrine disorder most
      commonly affecting women, suggesting a role for female hormones and/or their
      receptors in parathyroid adenomas. We here investigated the prolactin receptor
      (PRLr) which is associated with tumours of the breast and other organs.
      METHODOLOGY/PRINCIPAL FINDINGS: PRLr expression was investigated in a panel of 37
      patients with sporadic parathyroid tumours and its functionality in cultured
      parathyroid tumour cells. In comparison with other tissues and breast cancer
      cells, high levels of prolactin receptor gene (PRLR) transcripts were
      demonstrated in parathyroid tissues. PRLr products of 60/70 kDa were highly
      expressed in all parathyroid tumours. In addition varying levels of the 80 kDa
      PRLr isoform, with known proliferative activity, were demonstrated. In
      parathyroid tumours, PRLr immunoreactivity was observed in the cytoplasm (in all
      cases, n = 36), cytoplasmic granulae (n = 16), the plasma membrane (n = 12) or
      enlarged lysosomes (n = 4). In normal parathyroid rim (n = 28), PRLr was
      uniformly expressed in the cytoplasm and granulae. In in vitro studies of short
      term cultured human parathyroid tumour cells, prolactin stimulation was
      associated with significant transcriptional changes in JAK/STAT, RIG-I like
      receptor and type II interferon signalling pathways as documented by gene
      expression profiling. Moreover, PRLR gene expression in parathyroid tumours was
      inversely correlated with the patients' plasma calcium levels. CONCLUSIONS: We
      demonstrate that the prolactin receptor is highly abundant in human parathyroid
      tissues and that PRLr isoforms expression and PRLr subcellular localisation are
      altered in parathyroid tumours. Responsiveness of PRLr to physiological levels of
      prolactin was observed in the form of increased PTH secretion and altered gene
      transcription with significant increase of RIG-I like receptor, JAK-STAT and Type
      II interferon signalling pathways. These data suggest a role of the prolactin
      receptor in parathyroid adenomas.

PMID- 22606263
TI  - High nutrient transport and cycling potential revealed in the microbial
      metagenome of Australian sea lion (Neophoca cinerea) faeces.
AB  - Metagenomic analysis was used to examine the taxonomic diversity and metabolic
      potential of an Australian sea lion (Neophoca cinerea) gut microbiome. Bacteria
      comprised 98% of classifiable sequences and of these matches to Firmicutes (80%)
      were dominant, with Proteobacteria and Actinobacteria representing 8% and 2% of
      matches respectively. The relative proportion of Firmicutes (80%) to
      Bacteriodetes (2%) is similar to that in previous studies of obese humans and
      obese mice, suggesting the gut microbiome may confer a predisposition towards the
      excess body fat that is needed for thermoregulation within the cold oceanic
      habitats foraged by Australian sea lions. Core metabolic functions, including
      carbohydrate utilisation (14%), protein metabolism (9%) and DNA metabolism (7%)
      dominated the metagenome, but in comparison to human and fish gut microbiomes
      there was a significantly higher proportion of genes involved in phosphorus
      metabolism (2.4%) and iron scavenging mechanisms (1%). When sea lions defecate at
      sea, the relatively high nutrient metabolism potential of bacteria in their
      faeces may accelerate the dissolution of nutrients from faecal particles,
      enhancing their persistence in the euphotic zone where they are available to
      stimulate marine production.

PMID- 22606262
TI  - Shoc2 is targeted to late endosomes and required for Erk1/2 activation in EGF
      stimulated cells.
AB  - Shoc2 is the putative scaffold protein that interacts with RAS and RAF, and
      positively regulates signaling to extracellular signal-regulated protein kinases
      1 and 2 (ERK1/2). To elucidate the mechanism by which Shoc2 regulates ERK1/2
      activation by the epidermal growth factor (EGF) receptor (EGFR), we studied
      subcellular localization of Shoc2. Upon EGFR activation, endogenous Shoc2 and red
      fluorescent protein tagged Shoc2 were translocated from the cytosol to a subset
      of late endosomes containing Rab7. The endosomal recruitment of Shoc2 was blocked
      by overexpression of a GDP-bound H-RAS (N17S) mutant and RNAi knockdown of
      clathrin, suggesting the requirement of RAS activity and clathrin-dependent
      endocytosis. RNAi depletion of Shoc2 strongly inhibited activation of ERK1/2 by
      low, physiological EGF concentrations, which was rescued by expression of wild
      type recombinant Shoc2. In contrast, the Shoc2 (S2G) mutant, that is
      myristoylated and found in patients with the Noonan-like syndrome, did not rescue
      ERK1/2 activation in Shoc2-depleted cells. Shoc2 (S2G) was not located in late
      endosomes but was present on the plasma membrane and early endosomes. These data
      suggest that targeting of Shoc2 to late endosomes may facilitate EGFR-induced ERK
      activation under physiological conditions of cell stimulation by EGF, and
      therefore, may be involved in the spatiotemporal regulation of signaling through
      the RAS-RAF module.

PMID- 22606264
TI  - Localizing transcriptional regulatory elements at the mouse Dlk1 locus.
AB  - Much effort has focused recently on determining the mechanisms that control the
      allele-specific expression of genes subject to genomic imprinting, yet imprinting
      regulation is only one aspect of configuring appropriate expression of these
      genes. Imprinting control mechanisms must interact with those regulating the
      tissue-specific expression pattern of each imprinted gene in a cluster. Proper
      expression of the imprinted Delta-like 1 (Dlk1)-Maternally expressed gene 3
      (Meg3) gene pair is required for normal fetal development in mammals, yet the
      mechanisms that control tissue-specific expression of these genes are unknown. We
      have used a combination of in vivo and in vitro expression assays to localize cis
      regulatory elements that may regulate Dlk1 expression in the mouse embryo. A
      bacterial artificial chromosome transgene encompassing the Dlk1 gene and 77 kb of
      flanking sequence conferred expression in most endogenous Dlk1-expressing
      tissues. In combination with previous transgenic data, these experiments localize
      the majority of Dlk1 cis-regulatory elements to a 41 kb region upstream of the
      gene. Cross-species sequence conservation was used to further define potential
      regulatory elements, several of which functioned as enhancers in a luciferase
      expression assay. Two of these elements were able to drive expression of a lacZ
      reporter transgene in Dlk1-expressing tissues in the mouse embryo. The sequence
      proximal to Dlk1 therefore contains at least two discrete regions that may
      regulate tissue-specificity of Dlk1 expression.

PMID- 22606265
TI  - Transgenic expression of nonclassically secreted FGF suppresses kidney repair.
AB  - FGF1 is a signal peptide-less nonclassically released growth factor that is
      involved in angiogenesis, tissue repair, inflammation, and carcinogenesis. The
      effects of nonclassical FGF export in vivo are not sufficiently studied. We
      produced transgenic mice expressing FGF1 in endothelial cells (EC), which allowed
      the detection of FGF1 export to the vasculature, and studied the efficiency of
      postischemic kidney repair in these animals. Although FGF1 transgenic mice had a
      normal phenotype with unperturbed kidney structure, they showed a severely
      inhibited kidney repair after unilateral ischemia/reperfusion. This was
      manifested by a strong decrease of postischemic kidney size and weight, whereas
      the undamaged contralateral kidney exhibited an enhanced compensatory size
      increase. In addition, the postischemic kidneys of transgenic mice were
      characterized by hyperplasia of interstitial cells, paucity of epithelial tubular
      structures, increase of the areas occupied by connective tissue, and neutrophil
      and macrophage infiltration. The continuous treatment of transgenic mice with the
      cell membrane stabilizer, taurine, inhibited nonclassical FGF1 export and
      significantly rescued postischemic kidney repair. It was also found that similar
      to EC, the transgenic expression of FGF1 in monocytes and macrophages suppresses
      kidney repair. We suggest that nonclassical export may be used as a target for
      the treatment of pathologies involving signal peptide-less FGFs.

PMID- 22606266
TI  - A continental-wide perspective: the genepool of nuclear encoded ribosomal DNA and
      single-copy gene sequences in North American Boechera (Brassicaceae).
AB  - 74 of the currently accepted 111 taxa of the North American genus Boechera
      (Brassicaceae) were subject to pyhlogenetic reconstruction and network analysis.
      The dataset comprised 911 accessions for which ITS sequences were analyzed.
      Phylogenetic analyses yielded largely unresolved trees. Together with the network
      analysis confirming this result this can be interpreted as an indication for
      multiple, independent, and rapid diversification events. Network analyses were
      superimposed with datasets describing i) geographical distribution, ii) taxonomy,
      iii) reproductive mode, and iv) distribution history based on phylogeographic
      evidence. Our results provide first direct evidence for enormous reticulate
      evolution in the entire genus and give further insights into the evolutionary
      history of this complex genus on a continental scale. In addition two novel
      single-copy gene markers, orthologues of the Arabidopsis thaliana genes At2g25920
      and At3g18900, were analyzed for subsets of taxa and confirmed the findings
      obtained through the ITS data.

PMID- 22606267
TI  - Dcc regulates asymmetric outgrowth of forebrain neurons in zebrafish.
AB  - The guidance receptor DCC (deleted in colorectal cancer) ortholog UNC-40
      regulates neuronal asymmetry development in Caenorhabditis elegans, but it is not
      known whether DCC plays a role in the specification of neuronal polarity in
      vertebrates. To examine the roles of DCC in neuronal asymmetry regulation in
      vertebrates, we studied zebrafish anterior dorsal telencephalon (ADt) neuronal
      axons. We generated transgenic zebrafish animals expressing the photo-convertible
      fluorescent protein Kaede in ADt neurons and then photo-converted Kaede to label
      specifically the ADt neuron axons. We found that ADt axons normally project
      ventrally. Knock down of Dcc function by injecting antisense morpholino
      oligonucleotides caused the ADt neurons to project axons dorsally. To examine the
      axon projection pattern of individual ADt neurons, we labeled single ADt neurons
      using a forebrain-specific promoter to drive fluorescent protein expression. We
      found that individual ADt neurons projected axons dorsally or formed multiple
      processes after morpholino knock down of Dcc function. We further found that
      knock down of the Dcc ligand, Netrin1, also caused ADt neurons to project axons
      dorsally. Knockdown of Neogenin1, a guidance receptor closely related to Dcc,
      enhanced the formation of aberrant dorsal axons in embryos injected with Dcc
      morpholino. These experiments provide the first evidence that Dcc regulates
      polarized axon initiation and asymmetric outgrowth of forebrain neurons in
      vertebrates.

PMID- 22606268
TI  - A novel sLRP6E1E2 inhibits canonical Wnt signaling, epithelial-to-mesenchymal
      transition, and induces mitochondria-dependent apoptosis in lung cancer.
AB  - Aberrant activation of the Wnt pathway contributes to human cancer progression.
      Antagonists that interfere with Wnt ligand/receptor interactions can be useful in
      cancer treatments. In this study, we evaluated the therapeutic potential of a
      soluble Wnt receptor decoy in cancer gene therapy. We designed a Wnt antagonist
      sLRP6E1E2, and generated a replication-incompetent adenovirus (Ad), dE1
      k35/sLRP6E1E2, and a replication-competent oncolytic Ad, RdB-k35/sLRP6E1E2, both
      expressing sLRP6E1E2. sLRP6E1E2 prevented Wnt-mediated stabilization of
      cytoplasmic beta-catenin, decreased Wnt/beta-catenin signaling and cell
      proliferation via the mitogen-activated protein kinase, and phosphatidylinositol
      3-kinase pathways. sLRP6E1E2 induced apoptosis, cytochrome c release, and
      increased cleavage of PARP and caspase-3. sLRP6E1E2 suppressed growth of the
      human lung tumor xenograft, and reduced motility and invasion of cancer cells. In
      addition, sLRP6E1E2 upregulated expression of epithelial marker genes, while
      sLRP6E1E2 downregulated mesenchymal marker genes. Taken together, sLRP6E1E2, by
      inhibiting interaction between Wnt and its receptor, suppressed Wnt-induced cell
      proliferation and epithelial-to-mesenchymal transition.

PMID- 22606269
TI  - Gene transfer to chicks using lentiviral vectors administered via the embryonic
      chorioallantoic membrane.
AB  - The lack of affordable techniques for gene transfer in birds has inhibited the
      advancement of molecular studies in avian species. Here we demonstrate a new
      approach for introducing genes into chicken somatic tissues by administration of
      a lentiviral vector, derived from the feline immunodeficiency virus (FIV), into
      the chorioallantoic membrane (CAM) of chick embryos on embryonic day 11. The FIV
      derived vectors carried yellow fluorescent protein (YFP) or recombinant alpha
      melanocyte-stimulating hormone (alpha-MSH) genes, driven by the cytomegalovirus
      (CMV) promoter. Transgene expression, detected in chicks 2 days after hatch by
      quantitative real-time PCR, was mostly observed in the liver and spleen. Lower
      expression levels were also detected in the brain, kidney, heart and breast
      muscle. Immunofluorescence and flow cytometry analyses confirmed transgene
      expression in chick tissues at the protein level, demonstrating a transduction
      efficiency of ~0.46% of liver cells. Integration of the viral vector into the
      chicken genome was demonstrated using genomic repetitive (CR1)-PCR amplification.
      Viability and stability of the transduced cells was confirmed using terminal
      deoxynucleotidyl transferase (dUTP) nick end labeling (TUNEL) assay,
      immunostaining with anti-proliferating cell nuclear antigen (anti-PCNA), and
      detection of transgene expression 51 days post transduction. Our approach led to
      only 9% drop in hatching efficiency compared to non-injected embryos, and all of
      the hatched chicks expressed the transgenes. We suggest that the transduction
      efficiency of FIV vectors combined with the accessibility of the CAM vasculature
      as a delivery route comprise a new powerful and practical approach for gene
      delivery into somatic tissues of chickens. Most relevant is the efficient
      transduction of the liver, which specializes in the production and secretion of
      proteins, thereby providing an optimal target for prolonged study of secreted
      hormones and peptides.

PMID- 22606270
TI  - Molecular and functional characterization of the odorant receptor2 (OR2) in the
      tiger mosquito Aedes albopictus.
AB  - In mosquitoes, the olfactory system plays a crucial role in many types of
      behavior, including nectar feeding, host preference selection and oviposition.
      Aedes albopictus, known also as the tiger mosquito, is an anthropophilic species,
      which in the last few years, due to its strong ecological plasticity, has spread
      throughout the world. Although long considered only a secondary vector of
      viruses, the potential of its vector capacity may constitute a threat to public
      health. Based on the idea that an improved understanding of the olfactory system
      of mosquitoes may assist in the development of control methods that interfere
      with their behavior, we have undertaken a study aimed at characterizing the A.
      albopictus Odorant Receptors. Here we report the identification, cloning and
      functional characterization of the AalOR2 ortholog, that represents the first
      candidate member of the odorant receptor (OR) family of proteins from A.
      albopictus. AalOR2 is expressed in the larval heads and antennae of adults. Our
      data indicate that A. albopictus OR2 (AalOR2) shares a high degree of identity
      with other mosquito OR2 orthologs characterized to date, confirming that OR2 is
      one of the most conserved mosquito ORs. Our data indicate that AalOR2 is narrowly
      tuned to indole, and inhibited by (-)-menthone. In agreement with this results,
      these two compounds elicit two opposite effects on the olfactory-based behavior
      of A. albopictus larvae, as determined through a larval behavioral assay. In
      summary, this work has led to the cloning and de-orphaning of the first Odorant
      Receptor in the tiger mosquito A. albopictus. In future control strategies this
      receptor may be used as a potential molecular target.

PMID- 22606271
TI  - Characterising and predicting benthic biodiversity for conservation planning in
      deepwater environments.
AB  - Understanding patterns of biodiversity in deep sea systems is increasingly
      important because human activities are extending further into these areas.
      However, obtaining data is difficult, limiting the ability of science to inform
      management decisions. We have used three different methods of quantifying
      biodiversity to describe patterns of biodiversity in an area that includes two
      marine reserves in deep water off southern Australia. We used biological data
      collected during a recent survey, combined with extensive physical data to model,
      predict and map three different attributes of biodiversity: distributions of
      common species, beta diversity and rank abundance distributions (RAD). The
      distribution of each of eight common species was unique, although all the species
      respond to a depth-correlated physical gradient. Changes in composition (beta
      diversity) were large, even between sites with very similar environmental
      conditions. Composition at any one site was highly uncertain, and the suite of
      species changed dramatically both across and down slope. In contrast, the
      distributions of the RAD components of biodiversity (community abundance,
      richness, and evenness) were relatively smooth across the study area, suggesting
      that assemblage structure (i.e. the distribution of abundances of species) is
      limited, irrespective of species composition. Seamounts had similar biodiversity
      based on metrics of species presence, beta diversity, total abundance, richness
      and evenness to the adjacent continental slope in the same depth ranges. These
      analyses suggest that conservation objectives need to clearly identify which
      aspects of biodiversity are valued, and employ an appropriate suite of methods to
      address these aspects, to ensure that conservation goals are met.

PMID- 22606273
TI  - Parameter-free binarization and skeletonization of fiber networks from confocal
      image stacks.
AB  - We present a method to reconstruct a disordered network of thin biopolymers, such
      as collagen gels, from three-dimensional (3D) image stacks recorded with a
      confocal microscope. The method is based on a template matching algorithm that
      simultaneously performs a binarization and skeletonization of the network. The
      size and intensity pattern of the template is automatically adapted to the input
      data so that the method is scale invariant and generic. Furthermore, the template
      matching threshold is iteratively optimized to ensure that the final skeletonized
      network obeys a universal property of voxelized random line networks, namely,
      solid-phase voxels have most likely three solid-phase neighbors in a 3 x 3 x 3
      neighborhood. This optimization criterion makes our method free of user-defined
      parameters and the output exceptionally robust against imaging noise.

PMID- 22606272
TI  - Quantitative in situ measurement of estrogen receptor mRNA predicts response to
      tamoxifen.
AB  - PURPOSE: Quantification of mRNA has historically been done by reverse
      transcription polymerase chain reaction (RT-PCR). Recently, a robust method of
      detection of mRNA utilizing in situ hybridization has been described that is
      linear and shows high specificity with low background. Here we describe the use
      of the AQUA method of quantitative immunofluorescence (QIF) for measuring mRNA in
      situ using ESR1 (the estrogen receptor alpha gene) in breast cancer to determine
      its predictive value compared to Estrogen Receptor alpha (ER) protein. METHODS:
      Messenger RNA for ER (ESR1) and Ubiquitin C (UbC) were visualized using RNAscope
      probes and levels were quantified by quantitative in situ hybridization (qISH) on
      two Yale breast cancer cohorts on tissue microarrays. ESR1 levels were compared
      to ER protein levels measured by QIF using the SP1 antibody. RESULTS: ESR1 mRNA
      is reproducibly and specifically measurable by qISH on tissue collected from 1993
      or later. ESR1 levels were correlated to ER protein levels in a non-linear manner
      on two Yale cohorts. High levels of ESR1 were found to be predictive of response
      to tamoxifin. CONCLUSION: Quantification of mRNA using qISH may allow assessment
      of large cohorts with minimal formalin fixed, paraffin embedded tissue.
      Exploratory data using this method suggests that measurement of ESR1 mRNA levels
      may be predictive of response to endocrine therapy in a manner that is different
      from the predictive value of ER.

PMID- 22606274
TI  - Methylglyoxal mediates adipocyte proliferation by increasing phosphorylation of
      Akt1.
AB  - Methylglyoxal (MG) is a highly reactive metabolite physiologically presented in
      all biological systems. The effects of MG on diabetes and hypertension have been
      long recognized. In the present study, we investigated the potential role of MG
      in obesity, one of the most important factors to cause metabolic syndrome. An
      increased MG accumulation was observed in the adipose tissue of obese Zucker
      rats. Cell proliferation assay showed that 5-20 uM of MG stimulated the
      proliferation of 3T3-L1 cells. Further study suggested that accumulated-MG
      stimulated the phosphorylation of Akt1 and its targets including p21 and p27. The
      activated Akt1 then increased the activity of CDK2 and accelerated the cell cycle
      progression of 3T3-L1 cells. The effects of MG were efficiently reversed by
      advanced glycation end product (AGE) breaker alagebrium and Akt inhibitor SH-6.
      In summary, our study revealed a previously unrecognized effect of MG in
      stimulating adipogenesis by up-regulation of Akt signaling pathway and this
      mechanism might offer a new approach to explain the development of obesity.

PMID- 22606275
TI  - Miniaturized embryo array for automated trapping, immobilization and
      microperfusion of zebrafish embryos.
AB  - Zebrafish (Danio rerio) has recently emerged as a powerful experimental model in
      drug discovery and environmental toxicology. Drug discovery screens performed on
      zebrafish embryos mirror with a high level of accuracy the tests usually
      performed on mammalian animal models, and fish embryo toxicity assay (FET) is one
      of the most promising alternative approaches to acute ecotoxicity testing with
      adult fish. Notwithstanding this, automated in-situ analysis of zebrafish embryos
      is still deeply in its infancy. This is mostly due to the inherent limitations of
      conventional techniques and the fact that metazoan organisms are not easily
      susceptible to laboratory automation. In this work, we describe the development
      of an innovative miniaturized chip-based device for the in-situ analysis of
      zebrafish embryos. We present evidence that automatic, hydrodynamic positioning,
      trapping and long-term immobilization of single embryos inside the microfluidic
      chips can be combined with time-lapse imaging to provide real-time developmental
      analysis. Our platform, fabricated using biocompatible polymer molding
      technology, enables rapid trapping of embryos in low shear stress zones, uniform
      drug microperfusion and high-resolution imaging without the need of manual embryo
      handling at various developmental stages. The device provides a highly
      controllable fluidic microenvironment and post-analysis eleuthero-embryo stage
      recovery. Throughout the incubation, the position of individual embryos is
      registered. Importantly, we also for first time show that microfluidic embryo
      array technology can be effectively used for the analysis of anti-angiogenic
      compounds using transgenic zebrafish line (fli1a:EGFP). The work provides a new
      rationale for rapid and automated manipulation and analysis of developing
      zebrafish embryos at a large scale.

PMID- 22606276
TI  - Cluster analysis of obesity and asthma phenotypes.
AB  - BACKGROUND: Asthma is a heterogeneous disease with variability among patients in
      characteristics such as lung function, symptoms and control, body weight, markers
      of inflammation, and responsiveness to glucocorticoids (GC). Cluster analysis of
      well-characterized cohorts can advance understanding of disease subgroups in
      asthma and point to unsuspected disease mechanisms. We utilized an hypothesis
      free cluster analytical approach to define the contribution of obesity and
      related variables to asthma phenotype. METHODOLOGY AND PRINCIPAL FINDINGS: In a
      cohort of clinical trial participants (n = 250), minimum-variance hierarchical
      clustering was used to identify clinical and inflammatory biomarkers important in
      determining disease cluster membership in mild and moderate persistent
      asthmatics. In a subset of participants, GC sensitivity was assessed via
      expression of GC receptor alpha (GCRalpha) and induction of MAP kinase
      phosphatase-1 (MKP-1) expression by dexamethasone. Four asthma clusters were
      identified, with body mass index (BMI, kg/m(2)) and severity of asthma symptoms
      (AEQ score) the most significant determinants of cluster membership (F = 57.1,
      p<0.0001 and F = 44.8, p<0.0001, respectively). Two clusters were composed of
      predominantly obese individuals; these two obese asthma clusters differed from
      one another with regard to age of asthma onset, measures of asthma symptoms (AEQ)
      and control (ACQ), exhaled nitric oxide concentration (F(E)NO) and airway
      hyperresponsiveness (methacholine PC(20)) but were similar with regard to
      measures of lung function (FEV(1) (%) and FEV(1)/FVC), airway eosinophilia, IgE,
      leptin, adiponectin and C-reactive protein (hsCRP). Members of obese clusters
      demonstrated evidence of reduced expression of GCRalpha, a finding which was
      correlated with a reduced induction of MKP-1 expression by dexamethasone
      CONCLUSIONS AND SIGNIFICANCE: Obesity is an important determinant of asthma
      phenotype in adults. There is heterogeneity in expression of clinical and
      inflammatory biomarkers of asthma across obese individuals. Reduced expression of
      the dominant functional isoform of the GCR may mediate GC insensitivity in obese
      asthmatics.

PMID- 22606277
TI  - Evolution of neutral and flowering genes along pearl millet (Pennisetum glaucum)
      domestication.
AB  - BACKGROUND: Pearl millet landraces display an important variation in their cycle
      duration. This diversity contributes to the stability of crop production in the
      Sahel despite inter-annual rainfall fluctuation. Conservation of phenological
      diversity is important for the future of pearl millet improvement and sustainable
      use. Identification of genes contributing to flowering time variation is
      therefore relevant. In this study we focused on three flowering candidate genes,
      PgHd3a, PgDwarf8 and PgPHYC. We tested for signatures of past selective events
      within polymorphism patterns of these three genes that could have been associated
      with pearl millet domestication and/or landraces differentiation. In order to
      implement ad hoc neutrality tests, a plausible demographic history of pearl
      millet domestication was inferred through Approximate Bayesian Computation by
      using eight neutral STS loci. RESULTS: Domesticated pearl millet exhibited 84% of
      the nucleotide diversity level found in the wild population. No specific
      polymorphisms were found either in the wild or in the domestic populations. The
      bayesian approach and previous studies suggest that gene flow between wild
      relatives and domesticated pearl millets is a main factor explaining these
      results. Early and late landraces did not show significant genetic
      differentiation at both the neutral and the candidate loci. A positive selection
      was evidenced in PgHd3a and PgDwarf8 genes of domestic forms but not in the wild
      population. CONCLUSION: Our results strongly suggest that PgHd3a and PgDwarf8
      were likely targeted by selection during domestication. However, a potential role
      of any of the three candidate genes in the phenological differentiation between
      early and late landraces was not supported by our data. Reasons why these results
      contrast with previous results that have shown a slight but significant
      association between PgPHYC polymorphisms and variation in flowering time in pearl
      millet are discussed.

PMID- 22606278
TI  - Interoception across modalities: on the relationship between cardiac awareness
      and the sensitivity for gastric functions.
AB  - The individual sensitivity for ones internal bodily signals ("interoceptive
      awareness") has been shown to be of relevance for a broad range of cognitive and
      affective functions. Interoceptive awareness has been primarily assessed via
      measuring the sensitivity for ones cardiac signals ("cardiac awareness") which
      can be non-invasively measured by heartbeat perception tasks. It is an open
      question whether cardiac awareness is related to the sensitivity for other
      bodily, visceral functions. This study investigated the relationship between
      cardiac awareness and the sensitivity for gastric functions in healthy female
      persons by using non-invasive methods. Heartbeat perception as a measure for
      cardiac awareness was assessed by a heartbeat tracking task and gastric
      sensitivity was assessed by a water load test. Gastric myoelectrical activity was
      measured by electrogastrography (EGG) and subjective feelings of fullness,
      valence, arousal and nausea were assessed. The results show that cardiac
      awareness was inversely correlated with ingested water volume and with
      normogastric activity after water load. However, persons with good and poor
      cardiac awareness did not differ in their subjective ratings of fullness, nausea
      and affective feelings after drinking. This suggests that good heartbeat
      perceivers ingested less water because they subjectively felt more intense
      signals of fullness during this lower amount of water intake compared to poor
      heartbeat perceivers who ingested more water until feeling the same signs of
      fullness. These findings demonstrate that cardiac awareness is related to greater
      sensitivity for gastric functions, suggesting that there is a general sensitivity
      for interoceptive processes across the gastric and cardiac modality.

PMID- 22606279
TI  - Opuntia in Mexico: identifying priority areas for conserving biodiversity in a
      multi-use landscape.
AB  - BACKGROUND: Mexico is one of the world's centers of species diversity (richness)
      for Opuntia cacti. Yet, in spite of their economic and ecological importance,
      Opuntia species remain poorly studied and protected in Mexico. Many of the
      species are sparsely but widely distributed across the landscape and are subject
      to a variety of human uses, so devising implementable conservation plans for them
      presents formidable difficulties. Multi-criteria analysis can be used to design a
      spatially coherent conservation area network while permitting sustainable human
      usage. METHODS AND FINDINGS: Species distribution models were created for 60
      Opuntia species using MaxEnt. Targets of representation within conservation area
      networks were assigned at 100% for the geographically rarest species and 10% for
      the most common ones. Three different conservation plans were developed to
      represent the species within these networks using total area, shape, and
      connectivity as relevant criteria. Multi-criteria analysis and a metaheuristic
      adaptive tabu search algorithm were used to search for optimal solutions. The
      plans were built on the existing protected areas of Mexico and prioritized
      additional areas for management for the persistence of Opuntia species. All plans
      required around one-third of Mexico's total area to be prioritized for attention
      for Opuntia conservation, underscoring the implausibility of Opuntia conservation
      through traditional land reservation. Tabu search turned out to be both
      computationally tractable and easily implementable for search problems of this
      kind. CONCLUSIONS: Opuntia conservation in Mexico require the management of large
      areas of land for multiple uses. The multi-criteria analyses identified priority
      areas and organized them in large contiguous blocks that can be effectively
      managed. A high level of connectivity was established among the prioritized areas
      resulting in the enhancement of possible modes of plant dispersal as well as only
      a small number of blocks that would be recommended for conservation management.

PMID- 22606280
TI  - Differential actions of chlorhexidine on the cell wall of Bacillus subtilis and
      Escherichia coli.
AB  - Chlorhexidine is a chlorinated phenolic disinfectant used commonly in mouthwash
      for its action against bacteria. However, a comparative study of the action of
      chlorhexidine on the cell morphology of gram-positive and gram-negative bacteria
      is lacking. In this study, the actions of chlorhexidine on the cell morphology
      were identified with the aids of electron microscopy. After exposure to
      chlorhexidine, numerous spots of indentation on the cell wall were found in both
      Bacillus subtilis and Escherichia coli. The number of indentation spots increased
      with time of incubation and increasing chlorhexidine concentration.
      Interestingly, the dented spots found in B. subtilis appeared mainly at the
      hemispherical caps of the cells, while in E. coli the dented spots were found all
      over the cells. After being exposed to chlorhexidine for a prolonged period,
      leakage of cellular contents and subsequent ghost cells were observed, especially
      from B subtilis. By using 2-D gel/MS-MS analysis, five proteins related to purine
      nucleoside interconversion and metabolism were preferentially induced in the cell
      wall of E. coli, while three proteins related to stress response and four others
      in amino acid biosynthesis were up-regulated in the cell wall materials of B.
      subtilis. The localized morphological damages together with the biochemical and
      protein analysis of the chlorhexidine-treated cells suggest that chlorhexidine
      may act on the differentially distributed lipids in the cell membranes/wall of B.
      subtilis and E. coli.

PMID- 22606282
TI  - Phylogenetic and trait-based assembly of arbuscular mycorrhizal fungal
      communities.
AB  - Both competition and environmental filtering are expected to influence the
      community structure of microbes, but there are few tests of the relative
      importance of these processes because trait data on these organisms is often
      difficult to obtain. Using phylogenetic and functional trait information, we
      tested whether arbuscular mycorrhizal (AM) fungal community composition in an old
      field was influenced by competitive exclusion and/or environmental filtering.
      Communities at the site were dominated by species from the most speciose family
      of AM fungi, the Glomeraceae, though species from two other lineages, the
      Acaulosporaceae and Gigasporaceae were also found. Despite the dominance of
      species from a single family, AM fungal species most frequently co-existed when
      they were distantly related and when they differed in the ability to colonize
      root space on host plants. The ability of AM fungal species to colonize soil did
      not influence co-existence. These results suggest that competition between
      closely related and functionally similar species for space on plant roots
      influences community assembly. Nevertheless, in a substantial minority of cases
      communities were phylogenetically clustered, indicating that closely related
      species could also co-occur, as would be expected if i) the environment
      restricted community membership to single functional type or ii) competition
      among functionally similar species was weak. Our results therefore also suggest
      that competition for niche space between closely related fungi is not the sole
      influence of mycorrhizal community structure in field situations, but may be of
      greater relative importance than other ecological mechanisms.

PMID- 22606281
TI  - Cis-acting polymorphisms affect complex traits through modifications of microRNA
      regulation pathways.
AB  - Genome-wide association studies (GWAS) have become an effective tool to map genes
      and regions contributing to multifactorial human diseases and traits. A
      comparably small number of variants identified by GWAS are known to have a direct
      effect on protein structure whereas the majority of variants is thought to exert
      their moderate influences on the phenotype through regulatory changes in mRNA
      expression. MicroRNAs (miRNAs) have been identified as powerful
      posttranscriptional regulators of mRNAs. Binding to their target sites, which are
      mostly located within the 3'-untranslated region (3'-UTR) of mRNA transcripts,
      they modulate mRNA expression and stability. Until today almost all human mRNA
      transcripts are known to harbor at least one miRNA target site with an average of
      over 20 miRNA target sites per transcript. Among 5,101 GWAS-identified sentinel
      single nucleotide polymorphisms (SNPs) that correspond to 18,884 SNPs in linkage
      disequilibrium (LD) with the sentinels (r2 >= 0.8) we identified a significant
      overrepresentation of SNPs that affect the 3'-UTR of genes (OR = 2.33, 95% CI =
      2.12-2.57, P < 10(-52)). This effect was even stronger considering all SNPs in
      one LD bin a single signal (OR = 4.27, 95% CI = 3.84-4.74, P < 10(-114)). Based
      on crosslinking immunoprecipitation data we identified four mechanisms affecting
      miRNA regulation by 3'-UTR mutations: (i) deletion or (ii) creation of miRNA
      recognition elements within validated RNA-induced silencing complex binding
      sites, (iii) alteration of 3'-UTR splicing leading to a loss of binding sites,
      and (iv) change of binding affinity due to modifications of 3'-UTR folding. We
      annotated 53 SNPs of a total of 288 trait-associated 3'-UTR SNPs as mediating at
      least one of these mechanisms. Using a qualitative systems biology approach, we
      demonstrate how our findings can be used to support biological interpretation of
      GWAS results as well as to provide new experimentally testable hypotheses.

PMID- 22606283
TI  - The P-SSP7 cyanophage has a linear genome with direct terminal repeats.
AB  - P-SSP7 is a T7-like phage that infects the cyanobacterium Prochlorococcus MED4.
      MED4 is a member of the high-light-adapted Prochlorococcus ecotypes that are
      abundant in the surface oceans and contribute significantly to primary
      production. P-SSP7 has become a model system for the investigation of T7-like
      phages that infect Prochlorococcus. It was classified as T7-like based on genome
      content and organization. However, because its genome assembled as a circular
      molecule, it was thought to be circularly permuted and to lack the direct
      terminal repeats found in other T7-like phages. Here we sequenced the ends of the
      P-SSP7 genome and found that the genome map is linear and contains a 206 bp
      repeat at both genome ends. Furthermore, we found that a 728 bp region of the
      genome originally placed downstream of the last ORF is actually located upstream
      of the first ORF on the genome map. These findings suggest that P-SSP7 is likely
      to use the direct terminal repeats for genome replication and packaging in a
      similar manner to other T7-like phages. Moreover, these results highlight the
      importance of experimentally verifying the ends of phage genomes, and will
      facilitate the use of P-SSP7 as a model for the correct assembly and end
      determination of the many T7-like phages isolated from the marine environment
      that are currently being sequenced.

PMID- 22606284
TI  - Radiation-induced c-Jun activation depends on MEK1-ERK1/2 signaling pathway in
      microglial cells.
AB  - Radiation-induced normal brain injury is associated with acute and/or chronic
      inflammatory responses, and has been a major concern in radiotherapy. Recent
      studies suggest that microglial activation is a potential contributor to chronic
      inflammatory responses following irradiation; however, the molecular mechanism
      underlying the response of microglia to radiation is poorly understood. c-Jun, a
      component of AP-1 transcription factors, potentially regulates neural cell death
      and neuroinflammation. We observed a rapid increase in phosphorylation of N
      terminal c-Jun (on serine 63 and 73) and MAPK kinases ERK1/2, but not JNKs, in
      irradiated murine microglial BV2 cells. Radiation-induced c-Jun phosphorylation
      is dependent on the canonical MEK-ERK signaling pathway and required for both
      ERK1 and ERK2 function. ERK1/2 directly interact with c-Jun in vitro and in
      cells; meanwhile, the JNK binding domain on c-Jun is not required for its
      interaction with ERK kinases. Radiation-induced reactive oxygen species (ROS)
      potentially contribute to c-Jun phosphorylation through activating the ERK
      pathway. Radiation stimulates c-Jun transcriptional activity and upregulates c
      Jun-regulated proinflammatory genes, such as tumor necrosis factor-alpha,
      interleukin-1beta, and cyclooxygenase-2. Pharmacologic blockade of the ERK
      signaling pathway interferes with c-Jun activity and inhibits radiation
      stimulated expression of c-Jun target genes. Overall, our study reveals that the
      MEK-ERK1/2 signaling pathway, but not the JNK pathway, contributes to the c-Jun
      dependent microglial inflammatory response following irradiation.

PMID- 22606285
TI  - Dysfunction in fatty acid amide hydrolase is associated with depressive-like
      behavior in Wistar Kyoto rats.
AB  - BACKGROUND: While the etiology of depression is not clearly understood at the
      present time, this mental disorder is thought be a complex and multifactorial
      trait with important genetic and environmental contributing factors.
      METHODOLOGY/PRINCIPAL FINDINGS: The role of the endocannabinoid (eCB) system in
      depressive behavior was examined in Wistar Kyoto (WKY) rat strain, a genetic
      model of depression. Our findings revealed selective abnormalities in the eCB
      system in the brains of WKY rats compared to Wistar (WIS) rats. Immunoblot
      analysis indicated significantly higher levels of fatty acid amide hydrolase
      (FAAH) in frontal cortex and hippocampus of WKY rats with no alteration in the
      level of N-arachidonyl phosphatidyl ethanolamine specific phospholipase-D (NAPE
      PLD). Significantly higher levels of CB1 receptor-mediated G-protein coupling and
      lower levels of anandamide (AEA) were found in frontal cortex and hippocampus of
      WKY rats. While the levels of brain derived neurotropic factor (BDNF) were
      significantly lower in frontal cortex and hippocampus of WKY rats compared to WIS
      rats, pharmacological inhibition of FAAH elevated BDNF levels in WKY rats.
      Inhibition of FAAH enzyme also significantly increased sucrose consumption and
      decreased immobility in the forced swim test in WKY rats.
      CONCLUSIONS/SIGNIFICANCE: These findings suggest a critical role for the eCB
      system and BDNF in the genetic predisposition to depressive-like behavior in WKY
      rats and point to the potential therapeutic utility of eCB enhancing agents in
      depressive disorder.

PMID- 22606286
TI  - Cigarette smoking accelerated brain aging and induced pre-Alzheimer-like
      neuropathology in rats.
AB  - Cigarette smoking has been proposed as a major risk factor for aging-related
      pathological changes and Alzheimer's disease (AD). To date, little is known for
      how smoking can predispose our brains to dementia or cognitive impairment. This
      study aimed to investigate the cigarette smoke-induced pathological changes in
      brains. Male Sprague-Dawley (SD) rats were exposed to either sham air or 4%
      cigarette smoke 1 hour per day for 8 weeks in a ventilated smoking chamber to
      mimic the situation of chronic passive smoking. We found that the levels of
      oxidative stress were significantly increased in the hippocampus of the smoking
      group. Smoking also affected the synapse through reducing the expression of pre
      synaptic proteins including synaptophysin and synapsin-1, while there were no
      changes in the expression of postsynaptic protein PSD95. Decreased levels of
      acetylated-tubulin and increased levels of phosphorylated-tau at 231, 205 and 404
      epitopes were also observed in the hippocampus of the smoking rats. These results
      suggested that axonal transport machinery might be impaired, and the stability of
      cytoskeleton might be affected by smoking. Moreover, smoking affected amyloid
      precursor protein (APP) processing by increasing the production of sAPPbeta and
      accumulation of beta-amyloid peptide in the CA3 and dentate gyrus region. In
      summary, our data suggested that chronic cigarette smoking could induce synaptic
      changes and other neuropathological alterations. These changes might serve as
      evidence of early phases of neurodegeneration and may explain why smoking can
      predispose brains to AD and dementia.

PMID- 22606287
TI  - Suppression of the Nrf2-dependent antioxidant response by glucocorticoids and
      11beta-HSD1-mediated glucocorticoid activation in hepatic cells.
AB  - BACKGROUND: Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a key
      transcription factor regulating a plethora of detoxifying enzymes and antioxidant
      genes involved in drug metabolism and defence against oxidative stress. The
      glucocorticoid receptor (GR) is a ligand-induced transcription factor involved in
      the regulation of energy supply for metabolic needs to cope with various
      stressors. GR activity is controlled by glucocorticoids, which are synthesized in
      the adrenal glands and regenerated mainly in the liver from inactive cortisone by
      11beta-hydroxysteroid dehydrogenase-1 (11beta-HSD1). METHODS AND PRINCIPAL
      FINDINGS: Using transfected HEK-293 cells and hepatic H4IIE cells we show that
      glucocorticoids, activated by 11beta-HSD1 and acting through GR, suppress the
      Nrf2-dependent antioxidant response. The expression of the marker genes NQO1,
      HMOX1 and GST2A was suppressed upon treatment of 11beta-HSD1 expressing cells
      with cortisone, an effect that was reversed by 11beta-HSD1 inhibitors.
      Furthermore, our results demonstrate that elevated glucocorticoids lowered the
      ability of cells to detoxify H(2)O(2). Moreover, a comparison of gene expression
      in male and female rats revealed an opposite sexual dimorphism with an inverse
      relationship between 11beta-HSD1 and Nrf2 target gene expression. CONCLUSIONS:
      The results demonstrate a suppression of the cellular antioxidant defence
      capacity by glucocorticoids and suggest that elevated 11beta-HSD1 activity may
      lead to impaired Nrf2-dependent antioxidant response. The gender-specific
      differences in hepatic expression levels of 11beta-HSD1 and Nrf2 target genes and
      the impact of pharmacological inhibition of 11beta-HSD1 on improving cellular
      capacity to cope with oxidative stress warrants further studies in vivo.

PMID- 22606288
TI  - MGEx-Udb: a mammalian uterus database for expression-based cataloguing of genes
      across conditions, including endometriosis and cervical cancer.
AB  - BACKGROUND: Gene expression profiling of uterus tissue has been performed in
      various contexts, but a significant amount of the data remains underutilized as
      it is not covered by the existing general resources. METHODOLOGY/PRINCIPAL
      FINDINGS: We curated 2254 datasets from 325 uterus related mass scale gene
      expression studies on human, mouse, rat, cow and pig species. We then
      computationally derived a 'reliability score' for each gene's expression status
      (transcribed/dormant), for each possible combination of conditions and locations,
      based on the extent of agreement or disagreement across datasets. The data and
      derived information has been compiled into the Mammalian Gene Expression Uterus
      database (MGEx-Udb, http://resource.ibab.ac.in/MGEx-Udb/). The database can be
      queried with gene names/IDs, sub-tissue locations, as well as various conditions
      such as the cervical cancer, endometrial cycles and disorders, and experimental
      treatments. Accordingly, the output would be a) transcribed and dormant genes
      listed for the queried condition/location, or b) expression profile of the gene
      of interest in various uterine conditions. The results also include the
      reliability score for the expression status of each gene. MGEx-Udb also provides
      information related to Gene Ontology annotations, protein-protein interactions,
      transcripts, promoters, and expression status by other sequencing techniques, and
      facilitates various other types of analysis of the individual genes or co
      expressed gene clusters. CONCLUSIONS/SIGNIFICANCE: In brief, MGEx-Udb enables
      easy cataloguing of co-expressed genes and also facilitates bio-marker discovery
      for various uterine conditions.

PMID- 22606289
TI  - Patient enrolment into HIV care and treatment within 90 days of HIV diagnosis in
      eight Rwandan health facilities: a review of facility-based registers.
AB  - INTRODUCTION: Access to antiretroviral therapy (ART) has increased greatly in sub
      Saharan Africa. However many patients do not enrol timely into HIV care and
      treatment after HIV diagnosis. We studied enrolment into care and treatment and
      determinants of non-enrolment in Rwanda. METHODS: Data were obtained from routine
      clinic registers from eight health facilities in Rwanda on patients who were
      diagnosed with HIV at the antenatal care, voluntary counselling-and-testing,
      outpatient or tuberculosis departments between March and May 2009. The proportion
      of patients enrolled into HIV care and treatment was calculated as the number of
      HIV infected patients registered in ART clinics for follow-up care and treatment
      within 90 days of HIV diagnosis divided by the total number of persons diagnosed
      with HIV in the study period. RESULTS: Out of 482 patients diagnosed with HIV in
      the study period, 339 (70%) were females, and the median age was 29 years
      (interquartile range [IQR] 24-37). 201 (42%) enrolled into care and treatment
      within 90 days of HIV diagnosis. The median time between testing and enrolment
      was six days (IQR 2-14). Enrolment in care and treatment was not significantly
      associated with age, sex, or department of testing, but was associated with study
      site. None of those enrolled were in WHO stage 4. The median CD4 cell count among
      adult patients was 387 cells/mm(3) (IQR: 242-533 cells/mm(3)); 81 of 170 adult
      patients (48%) were eligible to start ART (CD4 count<350 cells/mm(3) or WHO stage
      4). Among those eligible, 45 (56%) started treatment within 90 days of HIV
      diagnosis. CONCLUSION: Less than 50% of diagnosed HIV patients from eight Rwandan
      health facilities had enrolled into care and treatment within 90 days of
      diagnosis. Improving linkage to care and treatment after HIV diagnosis is needed
      to harness the full potential of ART.

PMID- 22606291
TI  - Cyclin D1 G870A polymorphism contributes to colorectal cancer susceptibility:
      evidence from a systematic review of 22 case-control studies.
AB  - BACKGROUND: Cyclin D1 (CCND1) plays a vital role in cancer cell cycle
      progression. Numerous epidemiological studies have evaluated the association
      between the CCND1 G870A polymorphism and the risk of colorectal cancer. However,
      these studies have yielded conflicting results. To derive a more precise
      estimation of this association, we conducted a meta-analysis and systematic
      review. METHODOLOGY/PRINCIPAL FINDINGS: A comprehensive search was conducted to
      identify eligible studies of the CCND1 G870A polymorphism and colorectal cancer
      risk. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were derived
      from a fixed effect or random effect model. We applied a grading system (Venice
      criteria) that assessed the epidemiological strength of the association. A total
      of 22 publications that included 6157 cases and 8198 controls were identified. We
      found that the CCND1 G870A polymorphism was significantly associated with overall
      colorectal cancer risk (homozygote genetic model: OR = 1.130, 95% CI = 1.023
      1.248, P = 0.016; heterozygote genetic model: OR = 1.124, 95% CI = 1.030-1.226, P
      = 0.009; dominant genetic model: OR = 1.127, 95% CI = 1.037-1.224, P = 0.005).
      After further stratified analyses, the increased risk was observed only in the
      subgroups of hospital-based studies, PCR-RFLP genotyping methods, sporadic
      colorectal cancer, and Caucasian ethnicity. CONCLUSIONS: The available evidence
      demonstrates that the CCND1 870A allele might be a low-penetrant risk factor for
      colorectal cancer.

PMID- 22606290
TI  - Cross-phosphorylation, signaling and proliferative functions of the Tyro3 and Axl
      receptors in Rat2 cells.
AB  - The dysregulation of receptor protein tyrosine kinase (RPTK) function can result
      in changes in cell proliferation, cell growth and metastasis leading to malignant
      transformation. Among RPTKs, the TAM receptor family composed of three members
      Tyro3, Axl, and Mer has been recognized to have a prominent role in cell
      transformation. In this study we analyzed the consequences of Tyro3
      overexpression on cell proliferation, activation of signaling pathways and its
      functional interactions with Axl. Overexpression of Tyro3 in the Rat2 cell line
      that expresses Axl, but not Mer or Tyro3, resulted in a 5 fold increase in cell
      proliferation. This increase was partially blocked by inhibitors of the mitogen
      activated protein kinase (MAPK) signaling pathway but not by inhibitors of the
      phosphatidylinositol 3-kinase (PI(3)K) signaling pathway. Consistent with these
      findings, an increase in ERK1/2 phosphorylation was detected with Tyro3 but not
      with Axl overexpression. In contrast, activation of Axl stimulated the PI(3)K
      pathway, which was mitigated by co-expression of Tyro3. The overexpression of
      Tyro3 enhanced Gas6-mediated Axl phosphorylation, which was not detected upon
      overexpression of a "kinase dead" form of Tyro3 (kdTyro3). In addition, the
      overexpression of Axl induced kdTyro3 phosphorylation. Co-immunoprecipitation
      experiments confirmed that the Axl and Tyro3 receptors are closely associated.
      These findings show that overexpression of Tyro3 in the presence of Axl promotes
      cell proliferation, and that co-expression of Axl and Tyro3 can affect the
      outcome of Gas6-initiated signaling. Furthermore, they demonstrate a functional
      interaction between the members of the TAM receptor family which can shed light
      on the molecular mechanisms underlying the functional consequences of TAM
      receptor activation in cell transformation, neural function, immune function, and
      reproductive function among others.

PMID- 22606292
TI  - Hepatitis B virus alters the antioxidant system in transgenic mice and sensitizes
      hepatocytes to Fas signaling.
AB  - Hepatitis B virus (HBV) is a major etiological factor of hepatocellular carcinoma
      (HCC). However, the precise pathogenetic mechanisms linking HBV infection and HCC
      remain uncertain. It has been reported that decreased antioxidant enzyme
      activities are associated with severe liver injury and hepatocarcinogenesis in
      mouse models. It is unclear if HBV can interfere with the activities of
      antioxidant enzymes. We established a HBV transgenic mouse line, which
      spontaneously developed HCC at 2 years of age. We studied the activities of the
      antioxidant enzymes in the liver of the HBV transgenic mice. Our results showed
      that the antioxidant enzymes glutathione peroxidase and superoxide dismutase 2
      were down-regulated in HBV transgenic mice and correlated with JNK activation.
      HBV enhanced the Fas-mediated activation of caspase 6, caspase 8 and JNK without
      enhancing the activation of caspase 3 and hepatocellular apoptosis. As a proper
      redox balance is important for maintaining cellular homeostasis, these effects of
      HBV on the host antioxidant system and Fas-signaling may play an important role
      in HBV-induced hepatocarcinogenesis.

PMID- 22606293
TI  - Mechanisms underlying the link between cannabis use and prospective memory.
AB  - While the effects of cannabis use on retrospective memory have been extensively
      examined, only a limited number of studies have focused on the links between
      cannabis use and prospective memory. We conducted two studies to examine the
      links between cannabis use and both time-based and event-based prospective memory
      as well as potential mechanisms underlying these links. For the first study, 805
      students completed an online survey designed to assess cannabis consumption,
      problems with cannabis use indicative of a disorder, and frequency of
      experiencing prospective memory failures. The results showed small to moderate
      sized correlations between cannabis consumption, problems with cannabis use, and
      prospective memory. However, a series of mediation analyses revealed that
      correlations between problems with cannabis use and prospective memory were
      driven by self-reported problems with retrospective memory. For the second study,
      48 non-users (who had never used cannabis), 48 experimenters (who had used
      cannabis five or fewer times in their lives), and 48 chronic users (who had used
      cannabis at least three times a week for one year) were administered three
      objective prospective memory tests and three self-report measures of prospective
      memory. The results revealed no objective deficits in prospective memory
      associated with chronic cannabis use. In contrast, chronic cannabis users
      reported experiencing more internally-cued prospective memory failures.
      Subsequent analyses revealed that this effect was driven by self-reported
      problems with retrospective memory as well as by use of alcohol and other drugs.
      Although our samples were not fully characterized with respect to variables such
      as neurological disorders and family history of substance use disorders, leaving
      open the possibility that these variables may play a role in the detected
      relationships, the present findings indicate that cannabis use has a modest
      effect on self-reported problems with prospective memory, with a primary problem
      with retrospective memory appearing to underlie this relationship.

PMID- 22606294
TI  - Innate immune response of human plasmacytoid dendritic cells to poxvirus
      infection is subverted by vaccinia E3 via its Z-DNA/RNA binding domain.
AB  - Plasmacytoid dendritic cells (pDCs) play important roles in antiviral innate
      immunity by producing type I interferon (IFN). In this study, we assess the
      immune responses of primary human pDCs to two poxviruses, vaccinia and myxoma
      virus. Vaccinia, an orthopoxvirus, was used for immunization against smallpox, a
      contagious human disease with high mortality. Myxoma virus, a Leporipoxvirus,
      causes lethal disease in rabbits, but is non-pathogenic in humans. We report that
      myxoma virus infection of human pDCs induces IFN-alpha and TNF production,
      whereas vaccinia infection does not. Co-infection of pDCs with myxoma virus plus
      vaccinia blocks myxoma induction effects. We find that heat-inactivated vaccinia
      (Heat-VAC; by incubating the virus at 55 degrees C for 1 h) gains the ability to
      induce IFN-alpha and TNF in primary human pDCs. Induction of IFN-alpha in pDCs by
      myxoma virus or Heat-VAC is blocked by chloroquine, which inhibits endosomal
      acidification required for TLR7/9 signaling, and by inhibitors of cellular
      kinases PI3K and Akt. Using purified pDCs from genetic knockout mice, we
      demonstrate that Heat-VAC-induced type I IFN production in pDCs requires the
      endosomal RNA sensor TLR7 and its adaptor MyD88, transcription factor IRF7 and
      the type I IFN feedback loop mediated by IFNAR1. These results indicate that (i)
      vaccinia virus, but not myxoma virus, expresses inhibitor(s) of the poxvirus
      sensing pathway(s) in pDCs; and (ii) Heat-VAC infection fails to produce
      inhibitor(s) but rather produces novel activator(s), likely viral RNA transcripts
      that are sensed by the TLR7/MyD88 pathway. Using vaccinia gene deletion mutants,
      we show that the Z-DNA/RNA binding domain at the N-terminus of the vaccinia
      immunomodulatory E3 protein is an antagonist of the innate immune response of
      human pDCs to poxvirus infection and TLR agonists. The myxoma virus ortholog of
      vaccinia E3 (M029) lacks the N-terminal Z-DNA/RNA binding domain, which might
      contribute to the immunostimulating properties of myxoma virus.

PMID- 22606296
TI  - Overstimulation of NMDA receptors impairs early brain development in vivo.
AB  - BACKGROUND: Brains of patients with schizophrenia show both neurodevelopmental
      and functional deficits that suggest aberrant glutamate neurotransmission.
      Evidence from both genetic and pharmacological studies suggests that
      glutamatergic dysfunction, particularly with involvement of NMDARs, plays a
      critical role in the pathophysiology of schizophrenia. However, how prenatal
      disturbance of NMDARs leads to schizophrenia-associated developmental defects is
      largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: Glutamate transporter GLAST/GLT1
      double-knockout (DKO) mice carrying the NMDA receptor 1 subunit (NR1)-null
      mutation were generated. Bouin-fixed and paraffin-embedded embryonic day 16.5
      coronal brain sections were stained with hematoxylin, anti-microtubule-associated
      protein 2 (MAP2), and anti-L1 antibodies to visualize cortical, hippocampal, and
      olfactory bulb laminar structure, subplate neurons, and axonal projections. NR1
      deletion in DKO mice almost completely rescued multiple brain defects including
      cortical, hippocampal, and olfactory bulb disorganization and defective
      corticothalamic and thalamocortical axonal projections. CONCLUSIONS/SIGNIFICANCE:
      Excess glutamatergic signaling in the prenatal stage compromises early brain
      development via overstimulation of NMDARs.

PMID- 22606295
TI  - Neuregulin promotes incomplete autophagy of prostate cancer cells that is
      independent of mTOR pathway inhibition.
AB  - BACKGROUND: Growth factors activating the ErbB receptors have been described in
      prostate tumors. The androgen dependent prostate cancer cell line, LNCaP,
      expresses the ErbB-1, ErbB-2 and ErbB-3 receptor tyrosine kinases. Previously, it
      was demonstrated that NRG activates ErbB-2/ErbB-3 heterodimers to induce LNCaP
      cell death, whereas, EGF activates ErbB-1/ErbB-1 or ErbB-1/ErbB-2 dimers to
      induce cell growth and survival. It was also demonstrated that PI3K inhibitors
      repressed this cell death suggesting that in androgen deprived LNCaP cells, NRG
      activates a PI3K-dependent pathway associated with cell death.
      METHODOLOGY/PRINCIPAL FINDINGS: In the present study we demonstrate that NRG
      induces autophagy in LNCaP cells, using LC3 as a marker. However, the autophagy
      induced by NRG may be incomplete since p62 levels elevate. We also demonstrated
      that NRG- induced autophagy is independent of mammalian target of rapamycin
      (mTOR) inhibition since NRG induces Akt and S6K activation. Interestingly,
      inhibition of reactive oxygen species (ROS) by N-acetylcysteine (NAC), inhibited
      NRG-induced autophagy and cell death. Our study also identified JNK and Beclin 1
      as important components in NRG-induced autophagy and cell death. NRG induced
      elevation in JNK phosphorylation that was inhibited by NAC. Moreover, inhibitor
      of JNK inhibited NRG-induced autophagy and cell death. Also, in cells
      overexpressing Bcl-2 or cells expressing sh-RNA against Beclin 1, the effects of
      NRG, namely induction of autophagy and cell death, were inhibited.
      CONCLUSIONS/SIGNIFICANCE: Thus, in LNCaP cells, NRG-induces incomplete autophagy
      and cell death that depend on ROS levels. These effects of NRG are mediated by
      signaling pathway that activates JNK and Beclin 1, but is independent of mTOR
      inhibition.

PMID- 22606297
TI  - Functional changes in muscle afferent neurones in an osteoarthritis model:
      implications for impaired proprioceptive performance.
AB  - BACKGROUND: Impaired proprioceptive performance is a significant clinical issue
      for many who suffer osteoarthritis (OA) and is a risk factor for falls and other
      liabilities. This study was designed to evaluate weight-bearing distribution in a
      rat model of OA and to determine whether changes also occur in muscle afferent
      neurones. METHODOLOGY/PRINCIPAL FINDINGS: Intracellular recordings were made in
      functionally identified dorsal root ganglion neurones in acute
      electrophysiological experiments on the anaesthetized animal following
      measurements of hind limb weight bearing in the incapacitance test. OA rats but
      not naive control rats stood with less weight on the ipsilateral hind leg (P =
      0.02). In the acute electrophysiological experiments that followed weight bearing
      measurements, action potentials (AP) elicited by electrical stimulation of the
      dorsal roots differed in OA rats, including longer AP duration (P = 0.006),
      slower rise time (P = 0.001) and slower maximum rising rate (P = 0.03).
      Depolarizing intracellular current injection elicited more APs in models than in
      naive muscle afferent neurones (P = 0.01) indicating greater excitability. Axonal
      conduction velocity in model animals was slower (P = 0.04).
      CONCLUSIONS/SIGNIFICANCE: The present study demonstrates changes in hind limb
      stance accompanied by changes in the functional properties of muscle afferent
      neurones in this derangement model of OA. This may provide a possible avenue to
      explore mechanisms underlying the impaired proprioceptive performance and perhaps
      other sensory disorders in people with OA.

PMID- 22606298
TI  - Ventx factors function as Nanog-like guardians of developmental potential in
      Xenopus.
AB  - Vertebrate development requires progressive commitment of embryonic cells into
      specific lineages through a continuum of signals that play off differentiation
      versus multipotency. In mammals, Nanog is a key transcription factor that
      maintains cellular pluripotency by controlling competence to respond to
      differentiation cues. Nanog orthologs are known in most vertebrates examined to
      date, but absent from the Anuran amphibian Xenopus. Interestingly, in silico
      analyses and literature scanning reveal that basal vertebrate ventral homeobox
      (ventxs) and mammalian Nanog factors share extensive structural, evolutionary and
      functional properties. Here, we reassess the role of ventx activity in Xenopus
      laevis embryos and demonstrate that they play an unanticipated role as guardians
      of high developmental potential during early development. Joint over-expression
      of Xenopus ventx1.2 and ventx2.1-b (ventx1/2) counteracts lineage commitment
      towards both dorsal and ventral fates and prevents msx1-induced ventralization.
      Furthermore, ventx1/2 inactivation leads to down-regulation of the multipotency
      marker oct91 and to premature differentiation of blastula cells. Finally,
      supporting the key role of ventx1/2 in the control of developmental potential
      during development, mouse Nanog (mNanog) expression specifically rescues
      embryonic axis formation in ventx1/2 deficient embryos. We conclude that during
      Xenopus development ventx1/2 activity, reminiscent of that of Nanog in mammalian
      embryos, controls the switch of early embryonic cells from uncommitted to
      committed states.

PMID- 22606299
TI  - Congenital amusia persists in the developing brain after daily music listening.
AB  - Congenital amusia is a neurodevelopmental disorder that affects about 3% of the
      adult population. Adults experiencing this musical disorder in the absence of
      macroscopically visible brain injury are described as cases of congenital amusia
      under the assumption that the musical deficits have been present from birth.
      Here, we show that this disorder can be expressed in the developing brain. We
      found that (10-13 year-old) children exhibit a marked deficit in the detection of
      fine-grained pitch differences in both musical and acoustical context in
      comparison to their normally developing peers comparable in age and general
      intelligence. This behavioral deficit could be traced down to their abnormal P300
      brain responses to the detection of subtle pitch changes. The altered pattern of
      electrical activity does not seem to arise from an anomalous functioning of the
      auditory cortex, because all early components of the brain potentials, the N100,
      the MMN, and the P200 appear normal. Rather, the brain and behavioral measures
      point to disrupted information propagation from the auditory cortex to other
      cortical regions. Furthermore, the behavioral and neural manifestations of the
      disorder remained unchanged after 4 weeks of daily musical listening. These
      results show that congenital amusia can be detected in childhood despite regular
      musical exposure and normal intellectual functioning.

PMID- 22606300
TI  - STM2209-STM2208 (opvAB): a phase variation locus of Salmonella enterica involved
      in control of O-antigen chain length.
AB  - STM2209 and STM2208 are contiguous loci annotated as putative protein-coding
      genes in the chromosome of Salmonella enterica. Lack of homologs in related
      Enterobacteria and low G+C content suggest that S. enterica may have acquired
      STM2209-STM2208 by horizontal transfer. STM2209 and STM2208 are co-transcribed
      from a promoter upstream STM2209, and their products are inner (cytoplasmic)
      membrane proteins. Analysis with the bacterial adenylate cyclase two-hybrid
      system suggests that STM2209 and STM2208 may interact. Expression of STM2209
      STM2208 is subjected to phase variation in wild type Salmonella enterica serovar
      Typhimurium. Switching frequencies in LB medium are 6.1*10(-5) (OFF->ON) and
      3.7*10(-2) (ON->OFF) per cell and generation. Lack of DNA adenine methylation
      locks STM2209-STM2208 in the ON state, and lack of the LysR-type factor OxyR
      locks STM2209-STM2208 in the OFF state. OxyR-dependent activation of STM2209
      STM2208 expression is independent of the oxidation state of OxyR. Salmonella
      cultures locked in the ON state show alteration of O-antigen length in the
      lipopolysaccharide, reduced absorption of bacteriophage P22, impaired resistance
      to serum, and reduced proliferation in macrophages. Phenotypic heterogeneity
      generated by STM2209-STM2208 phase variation may thus provide defense against
      phages. In turn, formation of a subpopulation unable to proliferate in
      macrophages may restrain Salmonella spread in animal organs, potentially
      contributing to successful infection.

PMID- 22606301
TI  - Know your current I(h): interaction with a shunting current explains the puzzling
      effects of its pharmacological or pathological modulations.
AB  - The non-specific, hyperpolarization activated, I(h) current is particularly
      involved in epilepsy and it exhibits an excitatory or inhibitory action on
      synaptic integration in an apparently inconsistent way. It has been suggested
      that most of the inconsistencies could be reconciled invoking an indirect
      interaction with the M-type K(+) current, another current involved in epilepsy.
      However, here we show that the original experiments, and the simplified model
      used to explain and support them, cannot explain in a conclusive way the puzzling
      I(h) actions observed in different experimental preparations. Using a realistic
      model, we show instead how and why a shunting current, such as that carried by
      TASK-like channels, and dependent on I(h) channel is able to explain virtually
      all experimental findings on I(h) up- or down-regulation by modulators or
      pathological conditions. The model results suggest several experimentally
      testable predictions to characterize in more details this elusive and peculiar
      interaction, which may be of fundamental importance in the development of new
      treatments for all those pathological and cognitive dysfunctions caused,
      mediated, or affected by I(h).

PMID- 22606302
TI  - Complete chloroplast genome sequence of a major invasive species, crofton weed
      (Ageratina adenophora).
AB  - BACKGROUND: Crofton weed (Ageratina adenophora) is one of the most hazardous
      invasive plant species, which causes serious economic losses and environmental
      damages worldwide. However, the sequence resource and genome information of A.
      adenophora are rather limited, making phylogenetic identification and
      evolutionary studies very difficult. Here, we report the complete sequence of the
      A. adenophora chloroplast (cp) genome based on Illumina sequencing.
      METHODOLOGY/PRINCIPAL FINDINGS: The A. adenophora cp genome is 150, 689 bp in
      length including a small single-copy (SSC) region of 18, 358 bp and a large
      single-copy (LSC) region of 84, 815 bp separated by a pair of inverted repeats
      (IRs) of 23, 755 bp. The genome contains 130 unique genes and 18 duplicated in
      the IR regions, with the gene content and organization similar to other
      Asteraceae cp genomes. Comparative analysis identified five DNA regions (ndhD
      ccsA, psbI-trnS, ndhF-ycf1, ndhI-ndhG and atpA-trnR) containing parsimony
      informative characters higher than 2%, which may be potential informative markers
      for barcoding and phylogenetic analysis. Repeat structure, codon usage and
      contraction of the IR were also investigated to reveal the pattern of evolution.
      Phylogenetic analysis demonstrated a sister relationship between A. adenophora
      and Guizotia abyssinica and supported a monophyly of the Asterales. CONCLUSION:
      We have assembled and analyzed the chloroplast genome of A. adenophora in this
      study, which was the first sequenced plastome in the Eupatorieae tribe. The
      complete chloroplast genome information is useful for plant phylogenetic and
      evolutionary studies within this invasive species and also within the Asteraceae
      family.

PMID- 22606304
TI  - Effect of standard tuberculosis treatment on plasma cytokine levels in patients
      with active pulmonary tuberculosis.
AB  - BACKGROUND: Sputum Mycobacterium tuberculosis (Mtb) culture is commonly used to
      assess response to antibiotic treatment in individuals with pulmonary
      tuberculosis (TB). Such techniques are constrained by the slow growth rate of
      Mtb, and more sensitive methods to monitor Mtb clearance are needed. The goal of
      this study was to evaluate changes in plasma cytokines in patients undergoing
      treatment for TB as a means of identifying candidate host markers associated with
      microbiologic response to therapy. METHODS: Twenty-four plasma
      cytokines/chemokines were measured in 42 individuals diagnosed with active
      pulmonary TB, 52% were HIV co-infected. Individuals, undergoing a 26-week
      standard TB treatment, were followed longitudinally over 18 months and
      measurements were associated with HIV status and rates of sputum culture
      conversion. RESULTS: Plasma concentrations of interferon-inducible protein-10 (IP
      10) and vascular endothelial growth factor (VEGF) were significantly reduced upon
      TB treatment, regardless of HIV status. By the end of treatment, IP-10
      concentrations were significantly lower in HIV negative individuals when compared
      to HIV-positive individuals (p = 0.02). Moreover, in HIV negative patients,
      plasma VEGF concentrations, measured as early as 2-weeks post TB treatment
      initiation, positively correlated with the time of sputum conversion (p =
      0.0017). No significant changes were observed in other studied immune mediators.
      CONCLUSIONS: These data suggest that VEGF plasma concentration, measured during
      early TB treatment, could represent a surrogate marker to monitor sputum culture
      conversion in HIV uninfected individuals.

PMID- 22606305
TI  - Identification of maize genes associated with host plant resistance or
      susceptibility to Aspergillus flavus infection and aflatoxin accumulation.
AB  - BACKGROUND: Aspergillus flavus infection and aflatoxin contamination of maize
      pose negative impacts in agriculture and health. Commercial maize hybrids are
      generally susceptible to this fungus. Significant levels of host plant resistance
      have been observed in certain maize inbred lines. This study was conducted to
      identify maize genes associated with host plant resistance or susceptibility to
      A. flavus infection and aflatoxin accumulation. RESULTS: Genome wide gene
      expression levels with or without A. flavus inoculation were compared in two
      resistant maize inbred lines (Mp313E and Mp04:86) in contrast to two susceptible
      maize inbred lines (Va35 and B73) by microarray analysis. Principal component
      analysis (PCA) was used to find genes contributing to the larger variances
      associated with the resistant or susceptible maize inbred lines. The significance
      levels of gene expression were determined by using SAS and LIMMA programs. Fifty
      candidate genes were selected and further investigated by quantitative RT-PCR
      (qRT-PCR) in a time-course study on Mp313E and Va35. Sixteen of the candidate
      genes were found to be highly expressed in Mp313E and fifteen in Va35. Out of the
      31 highly expressed genes, eight were mapped to seven previously identified
      quantitative trait locus (QTL) regions. A gene encoding glycine-rich RNA binding
      protein 2 was found to be associated with the host hypersensitivity and
      susceptibility in Va35. A nuclear pore complex protein YUP85-like gene was found
      to be involved in the host resistance in Mp313E. CONCLUSION: Maize genes
      associated with host plant resistance or susceptibility were identified by a
      combination of microarray analysis, qRT-PCR analysis, and QTL mapping methods.
      Our findings suggest that multiple mechanisms are involved in maize host plant
      defense systems in response to Aspergillus flavus infection and aflatoxin
      accumulation. These findings will be important in identification of DNA markers
      for breeding maize lines resistant to aflatoxin accumulation.

PMID- 22606303
TI  - Depletion of cytotoxic T-cells does not protect NUP98-HOXD13 mice from
      myelodysplastic syndrome but reveals a modest tumor immunosurveillance effect.
AB  - Myelodysplastic syndrome (MDS) and aplastic anemia (AA) patients both present
      with symptoms of bone marrow failure. In many AA patients, these features are
      thought to result from an oligoclonal expansion of cytotoxic T-cells that destroy
      haematopoietic stem or progenitor cells. This notion is supported by the
      observation that AA patients respond to immunosuppressive therapy. A fraction of
      MDS patients also respond well to immunosuppressive therapy suggesting a similar
      role for cytotoxic T-cells in the etiology of MDS, however the role of cytotoxic
      T-cells in MDS remains unclear. Mice that express a NUP98-HOXD13 (NHD13)
      transgene develop a MDS that closely mimics the human condition in terms of
      dysplasia, ineffective hematopoiesis, and transformation to acute myeloid
      leukemia (AML). We followed a cohort of NHD13 mice lacking the Rag1 protein
      (NHD13/Rag1KO) to determine if the absence of lymphocytes might 1) delay the
      onset and/or diminish the severity of the MDS, or 2) effect malignant
      transformation and survival of the NHD13 mice. No difference was seen in the
      onset or severity of MDS between the NHD13 and NHD13/Rag1KO mice. However,
      NHD13/Rag1KO mice had decreased survival and showed a trend toward increased
      incidence of transformation to AML compared to the NHD13 mice, suggesting
      protection from AML transformation by a modest immuno-surveillance effect. In the
      absence of functional Tcrb signaling in the NHD13/Rag1KO T-cell tumors, Pak7 was
      identified as a potential Tcrb surrogate survival signal.

PMID- 22606306
TI  - Multiple processes regulate long-term population dynamics of sea urchins on
      Mediterranean rocky reefs.
AB  - We annually monitored the abundance and size structure of herbivorous sea urchin
      populations (Paracentrotus lividus and Arbacia lixula) inside and outside a
      marine reserve in the Northwestern Mediterranean on two distinct habitats
      (boulders and vertical walls) over a period of 20 years, with the aim of
      analyzing changes at different temporal scales in relation to biotic and abiotic
      drivers. P. lividus exhibited significant variability in density over time on
      boulder bottoms but not on vertical walls, and temporal trends were not
      significantly different between the protection levels. Differences in densities
      were caused primarily by variance in recruitment, which was less pronounced
      inside the MPA and was correlated with adult density, indicating density
      dependent recruitment under high predation pressure, as well as some positive
      feedback mechanisms that may facilitate higher urchin abundances despite higher
      predator abundance. Populations within the reserve were less variable in
      abundance and did not exhibit the hyper-abundances observed outside the reserve,
      suggesting that predation effects maybe more subtle than simply lowering the
      numbers of urchins in reserves. A. lixula densities were an order of magnitude
      lower than P. lividus densities and varied within sites and over time on boulder
      bottoms but did not differ between protection levels. In December 2008, an
      exceptionally violent storm reduced sea urchin densities drastically (by 50% to
      80%) on boulder substrates, resulting in the lowest values observed over the
      entire study period, which remained at that level for at least two years (up to
      the present). Our results also showed great variability in the biological and
      physical processes acting at different temporal scales. This study highlights the
      need for appropriate temporal scales for studies to fully understand ecosystem
      functioning, the concepts of which are fundamental to successful conservation and
      management.

PMID- 22606307
TI  - VENNTURE--a novel Venn diagram investigational tool for multiple pharmacological
      dataset analysis.
AB  - As pharmacological data sets become increasingly large and complex, new visual
      analysis and filtering programs are needed to aid their appreciation. One of the
      most commonly used methods for visualizing biological data is the Venn diagram.
      Currently used Venn analysis software often presents multiple problems to
      biological scientists, in that only a limited number of simultaneous data sets
      can be analyzed. An improved appreciation of the connectivity between multiple,
      highly-complex datasets is crucial for the next generation of data analysis of
      genomic and proteomic data streams. We describe the development of VENNTURE, a
      program that facilitates visualization of up to six datasets in a user-friendly
      manner. This program includes versatile output features, where grouped data
      points can be easily exported into a spreadsheet. To demonstrate its unique
      experimental utility we applied VENNTURE to a highly complex parallel paradigm,
      i.e. comparison of multiple G protein-coupled receptor drug dose phosphoproteomic
      data, in multiple cellular physiological contexts. VENNTURE was able to reliably
      and simply dissect six complex data sets into easily identifiable groups for
      straightforward analysis and data output. Applied to complex pharmacological
      datasets, VENNTURE's improved features and ease of analysis are much improved
      over currently available Venn diagram programs. VENNTURE enabled the delineation
      of highly complex patterns of dose-dependent G protein-coupled receptor activity
      and its dependence on physiological cellular contexts. This study highlights the
      potential for such a program in fields such as pharmacology, genomics, and
      bioinformatics.

PMID- 22606308
TI  - Evaluation of candidate reference genes for gene expression normalization in
      Brassica juncea using real time quantitative RT-PCR.
AB  - The real time quantitative reverse transcription PCR (qRT-PCR) is becoming
      increasingly important to gain insight into function of genes. Given the
      increased sensitivity, ease and reproducibility of qRT-PCR, the requirement of
      suitable reference genes for normalization has become important and stringent. It
      is now known that the expression of internal control genes in living organism
      vary considerably during developmental stages and under different experimental
      conditions. For economically important Brassica crops, only a couple of reference
      genes are reported till date. In this study, expression stability of 12 candidate
      reference genes including ACT2, ELFA, GAPDH, TUA, UBQ9 (traditional housekeeping
      genes), ACP, CAC, SNF, TIPS-41, TMD, TSB and ZNF (new candidate reference genes),
      in a diverse set of 49 tissue samples representing different developmental
      stages, stress and hormone treated conditions and cultivars of Brassica juncea
      has been validated. For the normalization of vegetative stages the ELFA, ACT2,
      CAC and TIPS-41 combination would be appropriate whereas TIPS-41 along with CAC
      would be suitable for normalization of reproductive stages. A combination of
      GAPDH, TUA, TIPS-41 and CAC were identified as the most suitable reference genes
      for total developmental stages. In various stress and hormone treated samples,
      UBQ9 and TIPS-41 had the most stable expression. Across five cultivars of B.
      juncea, the expression of CAC and TIPS-41 did not vary significantly and were
      identified as the most stably expressed reference genes. This study provides
      comprehensive information that the new reference genes selected herein performed
      better than the traditional housekeeping genes. The selection of most suitable
      reference genes depends on the experimental conditions, and is tissue and
      cultivar-specific. Further, to attain accuracy in the results more than one
      reference genes are necessary for normalization.

PMID- 22606309
TI  - Less is more: latent learning is maximized by shorter training sessions in
      auditory perceptual learning.
AB  - BACKGROUND: The time course and outcome of perceptual learning can be affected by
      the length and distribution of practice, but the training regimen parameters that
      govern these effects have received little systematic study in the auditory
      domain. We asked whether there was a minimum requirement on the number of trials
      within a training session for learning to occur, whether there was a maximum
      limit beyond which additional trials became ineffective, and whether multiple
      training sessions provided benefit over a single session. METHODOLOGY/PRINCIPAL
      FINDINGS: We investigated the efficacy of different regimens that varied in the
      distribution of practice across training sessions and in the overall amount of
      practice received on a frequency discrimination task. While learning was
      relatively robust to variations in regimen, the group with the shortest training
      sessions (~8 min) had significantly faster learning in early stages of training
      than groups with longer sessions. In later stages, the group with the longest
      training sessions (>1 hr) showed slower learning than the other groups,
      suggesting overtraining. Between-session improvements were inversely correlated
      with performance; they were largest at the start of training and reduced as
      training progressed. In a second experiment we found no additional longer-term
      improvement in performance, retention, or transfer of learning for a group that
      trained over 4 sessions (~4 hr in total) relative to a group that trained for a
      single session (~1 hr). However, the mechanisms of learning differed; the single
      session group continued to improve in the days following cessation of training,
      whereas the multi-session group showed no further improvement once training had
      ceased. CONCLUSIONS/SIGNIFICANCE: Shorter training sessions were advantageous
      because they allowed for more latent, between-session and post-training learning
      to emerge. These findings suggest that efficient regimens should use short
      training sessions, and optimized spacing between sessions.

PMID- 22606310
TI  - Immunomodulation by different types of N-oxides in the hemocytes of the marine
      bivalve Mytilus galloprovincialis.
AB  - The potential toxicity of engineered nanoparticles (NPs) for humans and the
      environment represents an emerging issue. Since the aquatic environment
      represents the ultimate sink for NP deposition, the development of suitable
      assays is needed to evaluate the potential impact of NPs on aquatic biota. The
      immune system is a sensitive target for NPs, and conservation of innate immunity
      represents an useful basis for studying common biological responses to NPs.
      Suspension-feeding invertebrates, such as bivalves, are particularly at risk to
      NP exposure, since they have extremely developed systems for uptake of nano and
      microscale particles integral to intracellular digestion and cellular immunity.
      Evaluation of the effects of NPs on functional parameters of bivalve immunocytes,
      the hemocytes, may help understanding the major toxic mechanisms and modes of
      actions that could be relevant for different NP types in aquatic organisms.In
      this work, a battery of assays was applied to the hemocytes of the marine bivalve
      Mytilus galloprovincialis to compare the in vitro effects of different n-oxides
      (n-TiO(2), n-SiO(2), n-ZnO, n-CeO(2)) chosen on the basis of their commercial and
      environmental relevance. Physico-chemical characterization of both primary
      particles and NP suspensions in artificial sea water-ASW was performed. Hemocyte
      lysosomal and mitochondrial parameters, oxyradical and nitric oxide production,
      phagocytic activity, as well as NP uptake, were evaluated. The results show that
      different n-oxides rapidly elicited differential responses hemocytes in relation
      to their chemical properties, concentration, behavior in sea water, and
      interactions with subcellular compartments. These represent the most extensive
      data so far available on the effects of NPs in the cells of aquatic organisms.
      The results indicate that Mytilus hemocytes can be utilized as a suitable model
      for screening the potential effects of NPs in the cells of aquatic invertebrates,
      and may provide a basis for future experimental work for designing
      environmentally safer nanomaterials.

PMID- 22606311
TI  - Differentiated human midbrain-derived neural progenitor cells express excitatory
      strychnine-sensitive glycine receptors containing alpha2beta subunits.
AB  - BACKGROUND: Human fetal midbrain-derived neural progenitor cells (NPCs) may
      deliver a tissue source for drug screening and regenerative cell therapy to treat
      Parkinson's disease. While glutamate and GABA(A) receptors play an important role
      in neurogenesis, the involvement of glycine receptors during human neurogenesis
      and dopaminergic differentiation as well as their molecular and functional
      characteristics in NPCs are largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here
      we investigated NPCs in respect to their glycine receptor function and subunit
      expression using electrophysiology, calcium imaging, immunocytochemistry, and
      quantitative real-time PCR. Whole-cell recordings demonstrate the ability of NPCs
      to express functional strychnine-sensitive glycine receptors after
      differentiation for 3 weeks in vitro. Pharmacological and molecular analyses
      indicate a predominance of glycine receptor heteromers containing alpha2beta
      subunits. Intracellular calcium measurements of differentiated NPCs suggest that
      glycine evokes depolarisations mediated by strychnine-sensitive glycine receptors
      and not by D-serine-sensitive excitatory glycine receptors. Culturing NPCs with
      additional glycine, the glycine-receptor antagonist strychnine, or the Na(+)-K(+)
      Cl(-) co-transporter 1 (NKCC1)-inhibitor bumetanide did not significantly
      influence cell proliferation and differentiation in vitro.
      CONCLUSIONS/SIGNIFICANCE: These data indicate that NPCs derived from human fetal
      midbrain tissue acquire essential glycine receptor properties during neuronal
      maturation. However, glycine receptors seem to have a limited functional impact
      on neurogenesis and dopaminergic differentiation of NPCs in vitro.

PMID- 22606312
TI  - Inferring carbon sources from gene expression profiles using metabolic flux
      models.
AB  - BACKGROUND: Bacteria have evolved the ability to efficiently and resourcefully
      adapt to changing environments. A key means by which they optimize their use of
      available nutrients is through adjustments in gene expression with consequent
      changes in enzyme activity. We report a new method for drawing environmental
      inferences from gene expression data. Our method prioritizes a list of candidate
      carbon sources for their compatibility with a gene expression profile using the
      framework of flux balance analysis to model the organism's metabolic network.
      PRINCIPAL FINDINGS: For each of six gene expression profiles for Escherichia coli
      grown under differing nutrient conditions, we applied our method to prioritize a
      set of eighteen different candidate carbon sources. Our method ranked the correct
      carbon source as one of the top three candidates for five of the six expression
      sets when used with a genome-scale model. The correct candidate ranked fifth in
      the remaining case. Additional analyses show that these rankings are robust with
      respect to biological and measurement variation, and depend on specific gene
      expression, rather than general expression level. The gene expression profiles
      are highly adaptive: simulated production of biomass averaged 94.84% of maximum
      when the in silico carbon source matched the in vitro source of the expression
      profile, and 65.97% when it did not. CONCLUSIONS: Inferences about a
      microorganism's nutrient environment can be made by integrating gene expression
      data into a metabolic framework. This work demonstrates that reaction flux limits
      for a model can be computed which are realistic in the sense that they affect in
      silico growth in a manner analogous to that in which a microorganism's alteration
      of gene expression is adaptive to its nutrient environment.

PMID- 22606313
TI  - Molecular evolution of a peptide GPCR ligand driven by artificial neural
      networks.
AB  - Peptide ligands of G protein-coupled receptors constitute valuable natural lead
      structures for the development of highly selective drugs and high-affinity tools
      to probe ligand-receptor interaction. Currently, pharmacological and metabolic
      modification of natural peptides involves either an iterative trial-and-error
      process based on structure-activity relationships or screening of peptide
      libraries that contain many structural variants of the native molecule. Here, we
      present a novel neural network architecture for the improvement of metabolic
      stability without loss of bioactivity. In this approach the peptide sequence
      determines the topology of the neural network and each cell corresponds one-to
      one to a single amino acid of the peptide chain. Using a training set, the
      learning algorithm calculated weights for each cell. The resulting network
      calculated the fitness function in a genetic algorithm to explore the virtual
      space of all possible peptides. The network training was based on gradient
      descent techniques which rely on the efficient calculation of the gradient by
      back-propagation. After three consecutive cycles of sequence design by the neural
      network, peptide synthesis and bioassay this new approach yielded a ligand with
      70fold higher metabolic stability compared to the wild type peptide without loss
      of the subnanomolar activity in the biological assay. Combining specialized
      neural networks with an exploration of the combinatorial amino acid sequence
      space by genetic algorithms represents a novel rational strategy for peptide
      design and optimization.

PMID- 22606314
TI  - Candida albicans-epithelial interactions: dissecting the roles of active
      penetration, induced endocytosis and host factors on the infection process.
AB  - Candida albicans frequently causes superficial infections by invading and
      damaging epithelial cells, but may also cause systemic infections by penetrating
      through epithelial barriers. C. albicans is a remarkable pathogen because it can
      invade epithelial cells via two distinct mechanisms: induced endocytosis,
      analogous to facultative intracellular enteropathogenic bacteria, and active
      penetration, similar to plant pathogenic fungi. Here we investigated the
      contributions of the two invasion routes of C. albicans to epithelial invasion.
      Using selective cellular inhibition approaches and differential fluorescence
      microscopy, we demonstrate that induced endocytosis contributes considerably to
      the early time points of invasion, while active penetration represents the
      dominant epithelial invasion route. Although induced endocytosis depends mainly
      on Als3-E-cadherin interactions, we observed E-cadherin independent induced
      endocytosis. Finally, we provide evidence of a protective role for serum factors
      in oral infection: human serum strongly inhibited C. albicans adhesion to,
      invasion and damage of oral epithelial cells.

PMID- 22606315
TI  - Diversity of bifidobacteria within the infant gut microbiota.
AB  - BACKGROUND: The human gastrointestinal tract (GIT) represents one of the most
      densely populated microbial ecosystems studied to date. Although this microbial
      consortium has been recognized to have a crucial impact on human health, its
      precise composition is still subject to intense investigation. Among the GIT
      microbiota, bifidobacteria represent an important commensal group, being among
      the first microbial colonizers of the gut. However, the prevalence and diversity
      of members of the genus Bifidobacterium in the infant intestinal microbiota has
      not yet been fully characterized, while some inconsistencies exist in literature
      regarding the abundance of this genus. METHODS/PRINCIPAL FINDINGS: In the current
      report, we assessed the complexity of the infant intestinal bifidobacterial
      population by analysis of pyrosequencing data of PCR amplicons derived from two
      hypervariable regions of the 16 S rRNA gene. Eleven faecal samples were collected
      from healthy infants of different geographical origins (Italy, Spain or Ireland),
      feeding type (breast milk or formula) and mode of delivery (vaginal or caesarean
      delivery), while in four cases, faecal samples of corresponding mothers were also
      analyzed. CONCLUSIONS: In contrast to several previously published culture
      independent studies, our analysis revealed a predominance of bifidobacteria in
      the infant gut as well as a profile of co-occurrence of bifidobacterial species
      in the infant's intestine.

PMID- 22606316
TI  - Effects of disturbance intensity and frequency on bacterial community composition
      and function.
AB  - Disturbances influence community structure and ecosystem functioning. Bacteria
      are key players in ecosystems and it is therefore crucial to understand the
      effect of disturbances on bacterial communities and how they respond to them,
      both compositionally and functionally. The main aim of this study was to test the
      effect of differences in disturbance strength on bacterial communities. For this,
      we implemented two independent short-term experiments with dialysis bags
      containing natural bacterial communities, which were transplanted between ambient
      and 'disturbed' incubation tanks, manipulating either the intensity or the
      frequency of a salinity disturbance. We followed changes in community composition
      by terminal restriction fragment analysis (T-RFLP) and measured various community
      functions (bacterial production, carbon substrate utilization profiles and rates)
      directly after and after a short period of recovery under ambient conditions.
      Increases in disturbance strength resulted in gradually stronger changes in
      bacterial community composition and functions. In the disturbance intensity
      experiment, the sensitivity to the disturbance and the ability of recovery
      differed between different functions. In the disturbance frequency experiment,
      effects on the different functions were more consistent and recovery was not
      observed. Moreover, in case of the intensity experiment, there was also a time
      lag in the responses of community composition and functions, with functional
      responses being faster than compositional ones. To summarize, our study shows
      that disturbance strength has the potential to change the functional performance
      and composition of bacterial communities. It further highlights that the overall
      effects, rates of recovery and the degree of congruence in the response patterns
      of community composition and functioning along disturbance gradients depend on
      the type of function and the character of the disturbance.

PMID- 22606317
TI  - Independent, rapid and targeted loss of highly repetitive DNA in natural and
      synthetic allopolyploids of Nicotiana tabacum.
AB  - Allopolyploidy (interspecific hybridisation and polyploidy) has played a
      significant role in the evolutionary history of angiosperms and can result in
      genomic, epigenetic and transcriptomic perturbations. We examine the immediate
      effects of allopolyploidy on repetitive DNA by comparing the genomes of synthetic
      and natural Nicotiana tabacum with diploid progenitors N. tomentosiformis
      (paternal progenitor) and N. sylvestris (maternal progenitor). Using next
      generation sequencing, a recently developed graph-based repeat identification
      pipeline, Southern blot and fluorescence in situ hybridisation (FISH) we
      characterise two highly repetitive DNA sequences (NicCL3 and NicCL7/30). Analysis
      of two independent high-throughput DNA sequencing datasets indicates NicCL3 forms
      1.6-1.9% of the genome in N. tomentosiformis, sequences that occur in multiple,
      discontinuous tandem arrays scattered over several chromosomes. Abundance
      estimates, based on sequencing depth, indicate NicCL3 is almost absent in N.
      sylvestris and has been dramatically reduced in copy number in the allopolyploid
      N. tabacum. Surprisingly elimination of NicCL3 is repeated in some synthetic
      lines of N. tabacum in their forth generation. The retroelement NicCL7/30, which
      occurs interspersed with NicCL3, is also under-represented but to a much lesser
      degree, revealing targeted elimination of the latter. Analysis of paired-end
      sequencing data indicates the tandem component of NicCL3 has been preferentially
      removed in natural N. tabacum, increasing the proportion of the dispersed
      component. This occurs across multiple blocks of discontinuous repeats and based
      on the distribution of nucleotide similarity among NicCL3 units, was concurrent
      with rounds of sequence homogenisation.

PMID- 22606318
TI  - Versatile toolbox for high throughput biochemical and functional studies with
      fluorescent fusion proteins.
AB  - Fluorescent fusion proteins are widely used to study protein localization and
      interaction dynamics in living cells. However, to fully characterize proteins and
      to understand their function it is crucial to determine biochemical
      characteristics such as enzymatic activity and binding specificity. Here we
      demonstrate an easy, reliable and versatile medium/high-throughput method to
      study biochemical and functional characteristics of fluorescent fusion proteins.
      Using a new system based on 96-well micro plates comprising an immobilized GFP
      binding protein (GFP-mulitTrap), we performed fast and efficient one-step
      purification of different GFP- and YFP-fusion proteins from crude cell lysate.
      After immobilization we determined highly reproducible binding ratios of cellular
      expressed GFP-fusion proteins to histone-tail peptides, DNA or selected RFP
      fusion proteins. In particular, we found Cbx1 preferentially binding to di-and
      trimethylated H3K9 that is abolished by phosphorylation of the adjacent serine.
      DNA binding assays showed, that the MBD domain of MeCP2 discriminates between
      fully methylated over unmethylated DNA and protein-protein interactions studies
      demonstrate, that the PBD domain of Dnmt1 is essential for binding to PCNA.
      Moreover, using an ELISA-based approach, we detected endogenous PCNA and histone
      H3 bound at GFP-fusions. In addition, we quantified the level of H3K4me2 on
      nucleosomes containing different histone variants. In summary, we present an
      innovative medium/high-throughput approach to analyse binding specificities of
      fluroescently labeled fusion proteins and to detect endogenous interacting
      factors in a fast and reliable manner in vitro.

PMID- 22606319
TI  - GIT2 acts as a potential keystone protein in functional hypothalamic networks
      associated with age-related phenotypic changes in rats.
AB  - The aging process affects every tissue in the body and represents one of the most
      complicated and highly integrated inevitable physiological entities. The
      maintenance of good health during the aging process likely relies upon the
      coherent regulation of hormonal and neuronal communication between the central
      nervous system and the periphery. Evidence has demonstrated that the optimal
      regulation of energy usage in both these systems facilitates healthy aging.
      However, the proteomic effects of aging in regions of the brain vital for
      integrating energy balance and neuronal activity are not well understood. The
      hypothalamus is one of the main structures in the body responsible for sustaining
      an efficient interaction between energy balance and neurological activity.
      Therefore, a greater understanding of the effects of aging in the hypothalamus
      may reveal important aspects of overall organismal aging and may potentially
      reveal the most crucial protein factors supporting this vital signaling
      integration. In this study, we examined alterations in protein expression in the
      hypothalami of young, middle-aged, and old rats. Using novel combinatorial
      bioinformatics analyses, we were able to gain a better understanding of the
      proteomic and phenotypic changes that occur during the aging process and have
      potentially identified the G protein-coupled receptor/cytoskeletal-associated
      protein GIT2 as a vital integrator and modulator of the normal aging process.

PMID- 22606320
TI  - Immunoregulatory protein profiles of necrotizing enterocolitis versus spontaneous
      intestinal perforation in preterm infants.
AB  - Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are
      the most common acute surgical emergencies associated with high morbidity and
      mortality in preterm infants. We aimed to compare the profiles of
      immunoregulatory proteins and identify novel mediators in plasma of NEC and SIP
      infants. We also investigated the expression of target genes in resected
      intestinal tissues and an enterocyte cell line. Using Cytokine Antibody Array
      assay, we reported the first comparative profiles of immunoregulatory proteins in
      plasma of NEC and SIP infants, and showed that dysregulated proteins belonged to
      functionally diversified categories, including pro- and anti-inflammation,
      angiogenesis, cell growth, wound healing, anti-apoptosis, cell adhesion and
      extracellular matrix reorganization. Validation by ELISA confirmed significantly
      higher concentrations of interleukin (IL)-6, angiopoietin (Ang)-2, soluble type
      II interleukin-1 receptor (sIL-1RII), and soluble urokinase-type plasminogen
      activator receptor (suPAR) in NEC infants compared with gestational age-matched
      control, and a lower level of an epidermal growth factor receptor, secreted form
      of receptor tyrosine-protein kinase ErbB3 (sErbB3), compared with SIP infants.
      mRNA expressions of IL1-RII and uPAR were up-regulated in resected bowel tissues
      from NEC infants, indicating that immunoregulation also occurred at the cellular
      level. In FHs-74 Int cells, Ang-2, IL1-RII and uPAR mRNA expressions were
      significantly induced by the combined treatment with lipopolysaccharide (LPS) and
      platelet activating factor (PAF). Our study provided plasmatic signatures of
      immunoregulatory proteins in NEC and SIP infants, and demonstrated involvement of
      multiple functional pathways. The magnitude of changes in these proteins was
      significantly more extensive in NEC infants, reflecting the different nature of
      injury and/or severity of inflammation. We speculate that dysregulation of IL-6,
      Ang-2, IL-1RII and uPAR occurred at both systemic and cellular levels, and
      probably mediated via LPS and endogeneous PAF signals. Such exaggerated
      immunologic responses may account for the high morbidity and mortality in NEC
      compared with SIP patients.

PMID- 22606321
TI  - A multi-platform flow device for microbial (co-) cultivation and microscopic
      analysis.
AB  - Novel microbial cultivation platforms are of increasing interest to researchers
      in academia and industry. The development of materials with specialized chemical
      and geometric properties has opened up new possibilities in the study of
      previously unculturable microorganisms and has facilitated the design of elegant,
      high-throughput experimental set-ups. Within the context of the international
      Genetically Engineered Machine (iGEM) competition, we set out to design,
      manufacture, and implement a flow device that can accommodate multiple growth
      platforms, that is, a silicon nitride based microsieve and a porous aluminium
      oxide based microdish. It provides control over (co-)culturing conditions similar
      to a chemostat, while allowing organisms to be observed microscopically. The
      device was designed to be affordable, reusable, and above all, versatile. To test
      its functionality and general utility, we performed multiple experiments with
      Escherichia coli cells harboring synthetic gene circuits and were able to
      quantitatively study emerging expression dynamics in real-time via fluorescence
      microscopy. Furthermore, we demonstrated that the device provides a unique
      environment for the cultivation of nematodes, suggesting that the device could
      also prove useful in microscopy studies of multicellular microorganisms.

PMID- 22606322
TI  - Profiles of multidrug resistance protein-1 in the peripheral blood mononuclear
      cells of patients with refractory epilepsy.
AB  - BACKGROUND: About one third of patients with epilepsy become refractory to
      therapy despite receiving adequate medical treatment, possibly from multidrug
      resistance. P-glycoprotein, encoded by multidrug resistance protein-1 (MDR1)
      gene, at the blood brain barrier is considered as a major factor mediating drug
      efflux and contributing to resistance. Given that peripheral blood mononuclear
      cells (PBMNCs) express MDR1, we investigated a MDR1 status of PBMNCs in various
      subsets of epilepsy patients and demonstrated their association with clinical
      characteristics. METHODOLOGY/PRINCIPAL FINDINGS: Clinical and MDR1 data were
      collected from 140 patients with epilepsy, 30 healthy volunteers, and 20 control
      patients taking anti-epileptic drugs. PBMNCs were isolated, and basal MDR1 levels
      and MDR1 conformational change levels were measured by flow cytometry. MDR1
      profiles were analyzed according to various clinical parameters, including
      seizure frequency and number of medications used in epilepsy patients. Epilepsy
      patients had a higher basal MDR1 level than non-epilepsy groups (p<0.01). Among
      epilepsy patients, there is a tendency for higher seizure frequency group to have
      higher basal MDR1 level (p = 0.059). The MDR1 conformational change level was
      significantly higher in the high-medication-use group than the low-use group (p =
      0.028). Basal MDR1 (OR = 1.16 [95% CI: 1.060-1.268]) and conformational change
      level (OR = 1.11 [95% CI: 1.02-1.20]) were independent predictors for seizure
      frequency and number of medications, respectively. CONCLUSIONS/SIGNIFICANCE: The
      MDR1 profile of PBMNCs is associated with seizure frequency and medication
      conditions in patients with epilepsy.

PMID- 22606324
TI  - Not all locations are created equal: exploring how adults hide and search for
      objects.
AB  - Little is known about the strategies people use to effectively hide objects from
      others, or to search for objects others have hidden. The present research extends
      a recent investigation of people's hiding and searching strategies in a simple
      room with 9 cache location. In the present studies, people hid and searched for
      three objects under more than 70 floor tiles in complex real and virtual rooms.
      Experiment 1 replicated several finding of Talbot et al within the more complex
      real and virtual environments. Specifically, people traveled further from origin
      and selected more dispersed locations when hiding than when searching.
      Experiments 2 and 3 showed that: 1) people were attracted to an area of darkness
      when searching and avoided locations close to a window when hiding, 2) when
      search attempts were limited to three choices, people searched farther from
      origin and dispersed their locations more when hiding than when searching, and 3)
      informing people that they would need to recover their hidden objects altered
      their hiding behavior and increased recovery accuracy. Across all experiments,
      consistencies in location preferences emerged, with more preference for the
      middle of the room during hiding and more preference for corners of the room
      during searching. Even though the same people participated in both the hiding and
      searching tasks, it appears that people use different strategies to select hiding
      places than to search for objects hidden by others.

PMID- 22606323
TI  - Direct and allosteric inhibition of the FGF2/HSPGs/FGFR1 ternary complex
      formation by an antiangiogenic, thrombospondin-1-mimic small molecule.
AB  - Fibroblast growth factors (FGFs) are recognized targets for the development of
      therapies against angiogenesis-driven diseases, including cancer. The formation
      of a ternary complex with the transmembrane tyrosine kinase receptors (FGFRs),
      and heparan sulphate proteoglycans (HSPGs) is required for FGF2 pro-angiogenic
      activity. Here by using a combination of techniques including Nuclear Magnetic
      Resonance, Molecular Dynamics, Surface Plasmon Resonance and cell-based binding
      assays we clarify the molecular mechanism of inhibition of an angiostatic small
      molecule, sm27, mimicking the endogenous inhibitor of angiogenesis,
      thrombospondin-1. NMR and MD data demonstrate that sm27 engages the heparin
      binding site of FGF2 and induces long-range dynamics perturbations along
      FGF2/FGFR1 interface regions. The functional consequence of the inhibitor binding
      is an impaired FGF2 interaction with both its receptors, as demonstrated by SPR
      and cell-based binding assays. We propose that sm27 antiangiogenic activity is
      based on a twofold-direct and allosteric-mechanism, inhibiting FGF2 binding to
      both its receptors.

PMID- 22606325
TI  - Type I interferons are associated with subclinical markers of cardiovascular
      disease in a cohort of systemic lupus erythematosus patients.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) patients have a striking increase
      in cardiovascular (CV) comorbidity not fully explained by the Framingham risk
      score. Recent evidence from in vitro studies suggests that type I interferons
      (IFN) could promote premature CV disease (CVD) in SLE. We assessed the
      association of type I IFN signatures with functional and anatomical evidence of
      vascular damage, and with biomarkers of CV risk in a cohort of lupus patients
      without overt CVD. METHODOLOGY/PRINCIPAL FINDINGS: Serum type I IFN activity
      (induction of five IFN-inducible genes; IFIGs) from 95 SLE patient and 38
      controls was quantified by real-time PCR. Flow mediated dilatation (FMD) of the
      brachial artery and carotid intima media thickness (CIMT) were quantified by
      ultrasound, and coronary calcification by computed tomography. Serum vascular
      biomarkers were measured by ELISA. We evaluated the effect of type I IFNs on FMD,
      CIMT and coronary calcification by first applying principal components analysis
      to combine data from five IFIGs into summary components that could be
      simultaneously modeled. Three components were derived explaining 97.1% of the
      total IFIG variation. Multivariable linear regression was utilized to investigate
      the association between the three components and other covariates, with the
      outcomes of FMD and CIMT; zero-inflated Poisson regression was used for modeling
      of coronary calcification. After controlling for traditional CV risk factors,
      enhanced serum IFN activity was significantly associated with decreased
      endothelial function in SLE patients and controls (p<0.05 for component 3),
      increased CIMT among SLE patients (p<0.01 for components 1 and 2), and severity
      of coronary calcification among SLE patients (p<0.001 for component 3).
      CONCLUSIONS: Type I IFNs are independently associated with atherosclerosis
      development in lupus patients without history of overt CVD and after controlling
      for Framingham risk factors. This study further supports the hypothesis that type
      I IFNs promote premature vascular damage in SLE.

PMID- 22606326
TI  - Peptide array X-linking (PAX): a new peptide-protein identification approach.
AB  - Many protein interaction domains bind short peptides based on canonical sequence
      consensus motifs. Here we report the development of a peptide array-based
      proteomics tool to identify proteins directly interacting with ligand peptides
      from cell lysates. Array-formatted bait peptides containing an amino acid-derived
      cross-linker are photo-induced to crosslink with interacting proteins from
      lysates of interest. Indirect associations are removed by high stringency washes
      under denaturing conditions. Covalently trapped proteins are subsequently
      identified by LC-MS/MS and screened by cluster analysis and domain scanning. We
      apply this methodology to peptides with different proline-containing consensus
      sequences and show successful identifications from brain lysates of known and
      novel proteins containing polyproline motif-binding domains such as EH, EVH1,
      SH3, WW domains. These results suggest the capacity of arrayed peptide ligands to
      capture and subsequently identify proteins by mass spectrometry is relatively
      broad and robust. Additionally, the approach is rapid and applicable to cell or
      tissue fractions from any source, making the approach a flexible tool for initial
      protein-protein interaction discovery.

PMID- 22606327
TI  - Plasticity of adult human pancreatic duct cells by neurogenin3-mediated
      reprogramming.
AB  - AIMS/HYPOTHESIS: Duct cells isolated from adult human pancreas can be
      reprogrammed to express islet beta cell genes by adenoviral transduction of the
      developmental transcription factor neurogenin3 (Ngn3). In this study we aimed to
      fully characterize the extent of this reprogramming and intended to improve it.
      METHODS: The extent of the Ngn3-mediated duct-to-endocrine cell reprogramming was
      measured employing genome wide mRNA profiling. By modulation of the Delta-Notch
      signaling or addition of pancreatic endocrine transcription factors Myt1, MafA
      and Pdx1 we intended to improve the reprogramming. RESULTS: Ngn3 stimulates duct
      cells to express a focused set of genes that are characteristic for islet
      endocrine cells and/or neural tissues. This neuro-endocrine shift however, is
      incomplete with less than 10% of full duct-to-endocrine reprogramming achieved.
      Transduction of exogenous Ngn3 activates endogenous Ngn3 suggesting auto
      activation of this gene. Furthermore, pancreatic endocrine reprogramming of human
      duct cells can be moderately enhanced by inhibition of Delta-Notch signaling as
      well as by co-expressing the transcription factor Myt1, but not MafA and Pdx1.
      CONCLUSIONS/INTERPRETATION: The results provide further insight into the
      plasticity of adult human duct cells and suggest measurable routes to enhance
      Ngn3-mediated in vitro reprogramming protocols for regenerative beta cell therapy
      in diabetes.

PMID- 22606328
TI  - Testing the fitness consequences of the thermoregulatory and parental care models
      for the origin of endothermy.
AB  - The origin of endothermy is a puzzling phenomenon in the evolution of
      vertebrates. To address this issue several explicative models have been proposed.
      The main models proposed for the origin of endothermy are the aerobic capacity,
      the thermoregulatory and the parental care models. Our main proposal is that to
      compare the alternative models, a critical aspect is to determine how strongly
      natural selection was influenced by body temperature, and basal and maximum
      metabolic rates during the evolution of endothermy. We evaluate these
      relationships in the context of three main hypotheses aimed at explaining the
      evolution of endothermy, namely the parental care hypothesis and two hypotheses
      related to the thermoregulatory model (thermogenic capacity and higher body
      temperature models). We used data on basal and maximum metabolic rates and body
      temperature from 17 rodent populations, and used intrinsic population growth rate
      (R(max)) as a global proxy of fitness. We found greater support for the
      thermogenic capacity model of the thermoregulatory model. In other words, greater
      thermogenic capacity is associated with increased fitness in rodent populations.
      To our knowledge, this is the first test of the fitness consequences of the
      thermoregulatory and parental care models for the origin of endothermy.

PMID- 22606329
TI  - Lack of Cul4b, an E3 ubiquitin ligase component, leads to embryonic lethality and
      abnormal placental development.
AB  - Cullin-RING ligases (CRLs) complexes participate in the regulation of diverse
      cellular processes, including cell cycle progression, transcription, signal
      transduction and development. Serving as the scaffold protein, cullins are
      crucial for the assembly of ligase complexes, which recognize and target various
      substrates for proteosomal degradation. Mutations in human CUL4B, one of the
      eight members in cullin family, are one of the major causes of X-linked mental
      retardation. We here report the generation and characterization of Cul4b knockout
      mice, in which exons 3 to 5 were deleted. In contrast to the survival to
      adulthood of human hemizygous males with CUL4B null mutation, Cul4b null mouse
      embryos show severe developmental arrest and usually die before embryonic day 9.5
      (E9.5). Accumulation of cyclin E, a CRL (CUL4B) substrate, was observed in Cul4b
      null embryos. Cul4b heterozygotes were recovered at a reduced ratio and exhibited
      a severe developmental delay. The placentas in Cul4b heterozygotes were
      disorganized and were impaired in vascularization, which may contribute to the
      developmental delay. As in human CUL4B heterozygotes, Cul4b null cells were
      selected against in Cul4b heterozygotes, leading to various degrees of skewed X
      inactivation in different tissues. Together, our results showed that CUL4B is
      indispensable for embryonic development in the mouse.

PMID- 22606330
TI  - Inhibition mechanism and model of an angiotensin I-converting enzyme (ACE)
      inhibitory hexapeptide from yeast (Saccharomyces cerevisiae).
AB  - Angiotensin I-converting enzyme (ACE) has an important function in blood pressure
      regulation. ACE-inhibitory peptides can lower blood pressure by inhibiting ACE
      activity. Based on the sequence of an ACE-inhibitory hexapeptide (TPTQQS)
      purified from yeast, enzyme kinetics experiments, isothermal titration
      calorimetry (ITC), and a docking simulation were performed. The hexapeptide was
      found to inhibit ACE in a non-competitive manner, as supported by the structural
      model. The hexapeptide bound to ACE via interactions of the N-terminal Thr1,
      Thr3, and Gln4 residues with the residues on the lid structure of ACE, and the C
      terminal Ser6 attracted the zinc ion, which is vital for ACE catalysis. The
      displacement of the zinc ion from the active site resulted in the inhibition of
      ACE activity. The structural model based on the docking simulation was supported
      by experiments in which the peptide was modified. This study provides a new
      inhibitory mechanism of ACE by a peptide which broads our knowledge for drug
      designing against enzyme targets.

PMID- 22606331
TI  - Non-uniform distribution pattern for differentially expressed genes of transgenic
      rice Huahui 1 at different developmental stages and environments.
AB  - DNA microarray analysis is an effective method to detect unintended effects by
      detecting differentially expressed genes (DEG) in safety assessment of
      genetically modified (GM) crops. With the aim to reveal the distribution of DEG
      of GM crops under different conditions, we performed DNA microarray analysis
      using transgenic rice Huahui 1 (HH1) and its non-transgenic parent Minghui 63
      (MH63) at different developmental stages and environmental conditions.
      Considerable DEG were selected in each group of HH1 under different conditions.
      For each group of HH1, the number of DEG was different; however, considerable
      common DEG were shared between different groups of HH1. These findings suggested
      that both DEG and common DEG were adequate for investigation of unintended
      effects. Furthermore, a number of significantly changed pathways were found in
      all groups of HH1, indicating genetic modification caused everlasting changes to
      plants. To our knowledge, our study for the first time provided the non-uniformly
      distributed pattern for DEG of GM crops at different developmental stages and
      environments. Our result also suggested that DEG selected in GM plants at
      specific developmental stage and environment could act as useful clues for
      further evaluation of unintended effects of GM plants.

PMID- 22606333
TI  - Transverse plane tendon and median nerve motion in the carpal tunnel: ultrasound
      comparison of carpal tunnel syndrome patients and healthy volunteers.
AB  - BACKGROUND: The median nerve and flexor tendons are known to translate
      transversely in the carpal tunnel. The purpose of this study was to investigate
      these motions in differential finger motion using ultrasound, and to compare them
      in healthy people and carpal tunnel syndrome patients. METHODS: Transverse
      ultrasounds clips were taken during fist, index finger, middle finger and thumb
      flexion in 29 healthy normal subjects and 29 CTS patients. Displacement in palmar
      dorsal and radial-ulnar direction was calculated using Analyze software.
      Additionally, the distance between the median nerve and the tendons was
      calculated. RESULTS: We found a changed motion pattern of the median nerve in
      middle finger, index finger and thumb motion between normal subjects and CTS
      patients (p<0.05). Also, we found a changed motion direction in CTS patients of
      the FDS III tendon in fist and middle finger motion, and of the FDS II and flexor
      pollicis longus tendon in index finger and thumb motion, respectively (p<0.05).
      The distance between the median nerve and the FDS II or FPL tendon is
      significantly greater in patients than in healthy volunteers for index finger and
      thumb motion, respectively (p<0.05). CONCLUSION: Our results suggest a changed
      motion pattern of the median nerve and several tendons in carpal tunnel syndrome
      patients compared to normal subjects. Such motion patterns may be useful in
      distinguishing affected from unaffected individuals, and in studies of the
      pathomechanics of carpal tunnel syndrome.

PMID- 22606332
TI  - Water extract from the leaves of Withania somnifera protect RA differentiated C6
      and IMR-32 cells against glutamate-induced excitotoxicity.
AB  - Glutamate neurotoxicity has been implicated in stroke, head trauma, multiple
      sclerosis and neurodegenerative disorders. Search for herbal remedies that may
      possibly act as therapeutic agents is an active area of research to combat these
      diseases. The present study was designed to investigate the neuroprotective role
      of Withania somnifera (Ashwagandha), also known as Indian ginseng, against
      glutamate induced toxicity in the retinoic acid differentiated rat glioma (C6)
      and human neuroblastoma (IMR-32) cells. The neuroprotective activity of the
      Ashwagandha leaves derived water extract (ASH-WEX) was evaluated. Cell viability
      and the expression of glial and neuronal cell differentiation markers was
      examined in glutamate challenged differentiated cells with and without the
      presence of ASH-WEX. We demonstrate that RA-differentiated C6 and IMR-32 cells,
      when exposed to glutamate, undergo loss of neural network and cell death that was
      accompanied by increase in the stress protein HSP70. ASH-WEX pre-treatment
      inhibited glutamate-induced cell death and was able to revert glutamate-induced
      changes in HSP70 to a large extent. Furthermore, the analysis on the neuronal
      plasticity marker NCAM (Neural cell adhesion molecule) and its polysialylated
      form, PSA-NCAM revealed that ASH-WEX has therapeutic potential for prevention of
      neurodegeneration associated with glutamate-induced excitotoxicty.

PMID- 22606334
TI  - Alpine crossroads or origin of genetic diversity? Comparative phylogeography of
      two sympatric microgastropod species.
AB  - The Alpine Region, constituting the Alps and the Dinaric Alps, has played a major
      role in the formation of current patterns of biodiversity either as a contact
      zone of postglacial expanding lineages or as the origin of genetic diversity. In
      our study, we tested these hypotheses for two widespread, sympatric
      microgastropod taxa--Carychium minimum O.F. Muller, 1774 and Carychium
      tridentatum (Risso, 1826) (Gastropoda, Eupulmonata, Carychiidae)--by using COI
      sequence data and species potential distribution models analyzed in a statistical
      phylogeographical framework. Additionally, we examined disjunct transatlantic
      populations of those taxa from the Azores and North America. In general, both
      Carychium taxa demonstrate a genetic structure composed of several differentiated
      haplotype lineages most likely resulting from allopatric diversification in
      isolated refugial areas during the Pleistocene glacial periods. However, the
      genetic structure of Carychium minimum is more pronounced, which can be
      attributed to ecological constraints relating to habitat proximity to permanent
      bodies of water. For most of the Carychium lineages, the broader Alpine Region
      was identified as the likely origin of genetic diversity. Several lineages are
      endemic to the broader Alpine Region whereas a single lineage per species
      underwent a postglacial expansion to (re)colonize previously unsuitable habitats,
      e.g. in Northern Europe. The source populations of those expanding lineages can
      be traced back to the Eastern and Western Alps. Consequently, we identify the
      Alpine Region as a significant 'hot-spot' for the formation of genetic diversity
      within European Carychium lineages. Passive dispersal via anthropogenic means
      best explains the presence of transatlantic European Carychium populations on the
      Azores and in North America. We conclude that passive (anthropogenic) transport
      could mislead the interpretation of observed phylogeographical patterns in
      general.

PMID- 22606335
TI  - Skin-targeted inhibition of PPAR beta/delta by selective antagonists to treat
      PPAR beta/delta-mediated psoriasis-like skin disease in vivo.
AB  - We have previously shown that peroxisome proliferator activating receptor
      beta/delta (PPAR beta/delta is overexpressed in psoriasis. PPAR beta/delta is not
      present in adult epidermis of mice. Targeted expression of PPAR beta/delta and
      activation by a selective synthetic agonist is sufficient to induce an
      inflammatory skin disease resembling psoriasis. Several signalling pathways
      dysregulated in psoriasis are replicated in this model, suggesting that PPAR
      beta/delta activation contributes to psoriasis pathogenesis. Thus, inhibition of
      PPAR beta/delta might harbour therapeutical potential. Since PPAR beta/delta has
      pleiotropic functions in metabolism, skin-targeted inhibition offer the potential
      of reducing systemic adverse effects. Here, we report that three selective PPAR
      beta/delta antagonists, GSK0660, compound 3 h, and GSK3787 can be formulated for
      topical application to the skin and that their skin concentration can be
      accurately quantified using ultra-high performance liquid chromatography
      (UPLC)/mass spectrometry. These antagonists show efficacy in our transgenic mouse
      model in reducing psoriasis-like changes triggered by activation of PPAR
      beta/delta. PPAR beta/delta antagonists GSK0660 and compound 3 do not exhibit
      systemic drug accumulation after prolonged application to the skin, nor do they
      induce inflammatory or irritant changes. Significantly, the irreversible PPAR
      beta/delta antagonist (GSK3787) retains efficacy when applied topically only
      three times per week which could be of practical clinical usefulness. Our data
      suggest that topical inhibition of PPAR beta/delta to treat psoriasis may warrant
      further exploration.

PMID- 22606336
TI  - De-novo transcriptome sequencing of a normalized cDNA pool from influenza
      infected ferrets.
AB  - The ferret is commonly used as a model for studies of infectious diseases. The
      genomic sequence of this animal model is not yet characterized, and only a
      limited number of fully annotated cDNAs are currently available in GenBank. The
      majority of genes involved in innate or adaptive immune response are still
      lacking, restricting molecular genetic analysis of host response in the ferret
      model. To enable de novo identification of transcriptionally active ferret genes
      in response to infection, we performed de-novo transcriptome sequencing of
      animals infected with H1N1 A/California/07/2009. We also included splenocytes
      induced with bacterial lipopolysaccharide to allow for identification of
      transcripts specifically induced by gram-negative bacteria. We pooled and
      normalized the cDNA library in order to delimit the risk of sequencing only
      highly expressed genes. While normalization of the cDNA library removes the
      possibility of assessing expression changes between individual animals, it has
      been shown to increase identification of low abundant transcripts. In this study,
      we identified more than 19,000 partial ferret transcripts, including more than
      1000 gene orthologs known to be involved in the innate and the adaptive immune
      response.

PMID- 22606337
TI  - In vivo effects of traditional Ayurvedic formulations in Drosophila melanogaster
      model relate with therapeutic applications.
AB  - BACKGROUND: Ayurveda represents the traditional medicine system of India. Since
      mechanistic details of therapy in terms of current biology are not available in
      Ayurvedic literature, modern scientific studies are necessary to understand its
      major concepts and procedures. It is necessary to examine effects of the whole
      Ayurvedic formulations rather than their "active" components as is done in most
      current studies. METHODS: We tested two different categories of formulations, a
      Rasayana (Amalaki Rasayana or AR, an herbal derivative) and a Bhasma (Rasa
      Sindoor or RS, an organo-metallic derivative of mercury), for effects on
      longevity, development, fecundity, stress-tolerance, and heterogeneous nuclear
      ribonucleoprotein (hnRNP) levels of Drosophila melanogaster using at least 200
      larvae or flies for each assay. RESULTS: A 0.5% (weight/volume) supplement of AR
      or RS affected life-history and other physiological traits in distinct ways.
      While the size of salivary glands, hnRNP levels in larval tissues, and
      thermotolerance of larvae/adult flies improved significantly following feeding
      either of the two formulations, the median life span and starvation resistance
      improved only with AR. Feeding on AR or RS supplemented food improved fecundity
      differently. Feeding of larvae and adults with AR increased the fecundity while
      the same with RS had opposite effect. On the contrary, feeding larvae on normal
      food and adults on AR supplement had no effect on fecundity but a comparable
      regime of feeding on RS-supplemented food improved fecundity. RS feeding did not
      cause heavy metal toxicity. CONCLUSIONS: The present study with two Ayurvedic
      formulations reveals formulation-specific effects on several parameters of the
      fly's life, which seem to generally agree with their recommended human usages in
      Ayurvedic practices. Thus, Drosophila, with its very rich genetic tools and well
      worked-out developmental pathways promises to be a very good model for examining
      the cellular and molecular bases of the effects of different Ayurvedic
      formulations.

PMID- 22606339
TI  - Can variation in hypothalamic-pituitary-adrenal (HPA)-axis activity explain the
      relationship between depression and cognition in bipolar patients?
AB  - BACKGROUND: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is
      thought to be associated with more mood symptoms and worse cognitive functioning.
      This study examined whether variation in HPA axis activity underlies the
      association between mood symptoms and cognitive functioning.
      METHODOLOGY/PRINCIPAL FINDINGS: In 65 bipolar patients cognitive functioning was
      measured in domains of psychomotor speed, speed of information processing,
      attentional switching, verbal memory, visual memory, executive functioning and an
      overall mean score. Severity of depression was assessed by the Inventory of
      Depressive Symptomatology-self rating version. Saliva cortisol measurements were
      performed to calculate HPA axis indicators: cortisol awakening response, diurnal
      slope, the evening cortisol level and the cortisol suppression on the
      dexamethasone suppression test. Regression analyses of depressive symptoms and
      cognitive functioning on each HPA axis indicator were performed. In addition we
      calculated percentages explanation of the association between depressive symptoms
      and cognition by HPA axis indicators. Depressive symptoms were associated with
      dysfunction in psychomotor speed, attentional switching and the mean score, as
      well as with attenuation in diurnal slope value. No association was found between
      HPA axis activity and cognitive functioning and HPA axis activity did not explain
      the associations between depressive symptoms and cognition.
      CONCLUSIONS/SIGNIFICANCE: As our study is the first one in this field specific
      for bipolar patients and changes in HPA-axis activity did not seem to explain the
      association between severity of depressive symptoms and cognitive functioning in
      bipolar patients, future studies are needed to evaluate other factors that might
      explain this relationship.

PMID- 22606338
TI  - What lies behind the wish to hasten death? A systematic review and meta
      ethnography from the perspective of patients.
AB  - BACKGROUND: There is a need for an in-depth approach to the meaning of the wish
      to hasten death (WTHD). This study aims to understand the experience of patients
      with serious or incurable illness who express such a wish. METHODS AND FINDINGS:
      Systematic review and meta-ethnography of qualitative studies from the patient's
      perspective. Studies were identified through six databases (ISI, PubMed,
      PsycINFO, CINAHL, CUIDEN and the Cochrane Register of Controlled Trials),
      together with citation searches and consultation with experts. Finally, seven
      studies reporting the experiences of 155 patients were included. The seven-stage
      Noblit and Hare approach was applied, using reciprocal translation and line-of
      argument synthesis. Six main themes emerged giving meaning to the WTHD: WTHD in
      response to physical/psychological/spiritual suffering, loss of self, fear of
      dying, the desire to live but not in this way, WTHD as a way of ending suffering,
      and WTHD as a kind of control over one's life ('having an ace up one's sleeve
      just in case'). An explanatory model was developed which showed the WTHD to be a
      reactive phenomenon: a response to multidimensional suffering, rather than only
      one aspect of the despair that may accompany this suffering. According to this
      model the factors that lead to the emergence of WTHD are total suffering, loss of
      self and fear, which together produce an overwhelming emotional distress that
      generates the WTHD as a way out, i.e. to cease living in this way and to put an
      end to suffering while maintaining some control over the situation. CONCLUSIONS:
      The expression of the WTHD in these patients is a response to overwhelming
      emotional distress and has different meanings, which do not necessarily imply a
      genuine wish to hasten one's death. These meanings, which have a causal
      relationship to the phenomenon, should be taken into account when drawing up care
      plans.

PMID- 22606340
TI  - Rapid transcriptional pulsing dynamics of high expressing retroviral transgenes
      in embryonic stem cells.
AB  - Single cell imaging studies suggest that transcription is not continuous and
      occurs as discrete pulses of gene activity. To study mechanisms by which
      retroviral transgenes can transcribe to high levels, we used the MS2 system to
      visualize transcriptional dynamics of high expressing proviral integration sites
      in embryonic stem (ES) cells. We established two ES cell lines each bearing a
      single copy, self-inactivating retroviral vector with a strong ubiquitous human
      EF1alpha gene promoter directing expression of mRFP fused to an MS2-stem-loop
      array. Transfection of MS2-EGFP generated EGFP focal dots bound to the mRFP-MS2
      stem loop mRNA. These transcription foci colocalized with the transgene
      integration site detected by immunoFISH. Live tracking of single cells for 20
      minutes detected EGFP focal dots that displayed frequent and rapid fluctuations
      in transcription over periods as short as 25 seconds. Similarly rapid
      fluctuations were detected from focal doublet signals that colocalized with
      replicated proviral integration sites by immunoFISH, consistent with
      transcriptional pulses from sister chromatids. We concluded that retroviral
      transgenes experience rapid transcriptional pulses in clonal ES cell lines that
      exhibit high level expression. These events are directed by a constitutive
      housekeeping gene promoter and may provide precedence for rapid transcriptional
      pulsing at endogenous genes in mammalian stem cells.

PMID- 22606341
TI  - An ileal Crohn's disease gene signature based on whole human genome expression
      profiles of disease unaffected ileal mucosal biopsies.
AB  - Previous genome-wide expression studies have highlighted distinct gene expression
      patterns in inflammatory bowel disease (IBD) compared to control samples, but the
      interpretation of these studies has been limited by sample heterogeneity with
      respect to disease phenotype, disease activity, and anatomic sites. To further
      improve molecular classification of inflammatory bowel disease phenotypes we
      focused on a single anatomic site, the disease unaffected proximal ileal margin
      of resected ileum, and three phenotypes that were unlikely to overlap: ileal
      Crohn's disease (ileal CD), ulcerative colitis (UC), and control patients without
      IBD. Whole human genome (Agilent) expression profiling was conducted on two
      independent sets of disease-unaffected ileal samples collected from the proximal
      margin of resected ileum. Set 1 (47 ileal CD, 27 UC, and 25 Control non-IBD
      patients) was used as the training set and Set 2 was subsequently collected as an
      independent test set (10 ileal CD, 10 UC, and 10 control non-IBD patients). We
      compared the 17 gene signatures selected by four different feature-selection
      methods to distinguish ileal CD phenotype with non-CD phenotype. The four methods
      yielded different but overlapping solutions that were highly discriminating. All
      four of these methods selected FOLH1 as a common feature. This gene is an
      established biomarker for prostate cancer, but has not previously been associated
      with Crohn's disease. Immunohistochemical staining confirmed increased expression
      of FOLH1 in the ileal epithelium. These results provide evidence for convergent
      molecular abnormalities in the macroscopically disease unaffected proximal margin
      of resected ileum from ileal CD subjects.

PMID- 22606342
TI  - Selective enrichment and sequencing of whole mitochondrial genomes in the
      presence of nuclear encoded mitochondrial pseudogenes (numts).
AB  - Numts are an integral component of many eukaryote genomes offering a snapshot of
      the evolutionary process that led from the incorporation of an alpha
      proteobacterium into a larger eukaryotic cell some 1.8 billion years ago.
      Although numt sequence can be harnessed as molecular marker, these sequences
      often remain unidentified and are mistaken for genuine mtDNA leading to erroneous
      interpretation of mtDNA data sets. It is therefore indispensable that during the
      process of amplifying and sequencing mitochondrial genes, preventive measures are
      taken to ensure the exclusion of numts to guarantee the recovery of genuine
      mtDNA. This applies to mtDNA analyses in general but especially to studies where
      mtDNAs are sequenced de novo as the launch pad for subsequent mtDNA-based
      research. By using a combination of dilution series and nested rolling circle
      amplification (RCA), we present a novel strategy to selectively amplify mtDNA and
      exclude the amplification of numt sequence. We have successfully applied this
      strategy to de novo sequence the mtDNA of the Black Field Cricket Teleogryllus
      commodus, a species known to contain numts. Aligning our assembled sequence to
      the reference genome of Teleogryllus emma (GenBank EU557269.1) led to the
      identification of a numt sequence in the reference sequence. This unexpected
      result further highlights the need of a reliable and accessible strategy to
      eliminate this source of error.

PMID- 22606343
TI  - Functional characterization of the infection-inducible peptide Edin in Drosophila
      melanogaster.
AB  - Drosophila is a well-established model organism for studying innate immunity
      because of its high resistance against microbial infections and lack of adaptive
      immunity. In addition, the immune signaling cascades found in Drosophila are
      evolutionarily conserved. Upon infection, activation of the immune signaling
      pathways, Toll and Imd, leads to the expression of multiple immune response
      genes, such as the antimicrobial peptides (AMPs). Previously, we identified an
      uncharacterized gene edin among the genes, which were strongly induced upon
      stimulation with Escherichia coli in Drosophila S2 cells. Edin has been
      associated with resistance against Listeria monocytogenes, but its role in
      Drosophila immunity remains elusive. In this study, we examined the role of Edin
      in the immune response of Drosophila both in vitro and in vivo. We report that
      edin expression is dependent on the Imd-pathway NF-kappaB transcription factor
      Relish and that it is expressed upon infection both in vitro and in vivo. Edin
      encodes a pro-protein, which is further processed in S2 cells. In our
      experiments, Edin did not bind microbes, nor did it possess antimicrobial
      activity to tested microbial strains in vitro or in vivo. Furthermore, edin RNAi
      did not significantly affect the expression of AMPs in vitro or in vivo. However,
      edin RNAi flies showed modestly impaired resistance to E. faecalis infection. We
      conclude that Edin has no potent antimicrobial properties but it appears to be
      important for E. faecalis infection via an uncharacterized mechanism. Further
      studies are still required to elucidate the exact role of Edin in the Drosophila
      immune response.

PMID- 22606344
TI  - Association of enhanced HIV-1 neutralization by a single Y681H substitution in
      gp41 with increased gp120-CD4 interaction and macrophage infectivity.
AB  - HIV-1 variants that show unusual sensitivity to autologous antibodies due to
      presence of critical neutralization signatures would likely contribute towards
      rational envelope based HIV-1 vaccine design. In the present study, we found that
      presence of a naturally occurring H681 in gp41 membrane proximal external region
      (MPER) of a clade C envelope (Env) obtained from a recently infected Indian
      patient conferred increased sensitivity to autologous and heterologous plasma
      antibodies. Furthermore, Env-pseudotyped viruses expressing H681 showed increased
      sensitivity to soluble CD4, b12 and 4E10 monoclonal antibodies both in related
      and unrelated Envs and was corroborated with increased Env susceptibility and
      binding to cellular CD4 as well as with prolonged exposure of MPER epitopes. The
      increased gp120-CD4 interaction was further associated with relative exposure of
      CD4-induced epitopes and macrophage infectivity. In summary, our data indicate
      that Y681H substitution exposes neutralizing epitopes in CD4bs and MPER towards
      comprehensive interference in HIV-1 entry.

PMID- 22606345
TI  - Gene expression profiling of liver cancer stem cells by RNA-sequencing.
AB  - BACKGROUND: Accumulating evidence supports that tumor growth and cancer relapse
      are driven by cancer stem cells. Our previous work has demonstrated the existence
      of CD90(+) liver cancer stem cells (CSCs) in hepatocellular carcinoma (HCC).
      Nevertheless, the characteristics of these cells are still poorly understood. In
      this study, we employed a more sensitive RNA-sequencing (RNA-Seq) to compare the
      gene expression profiling of CD90(+) cells sorted from tumor (CD90(+)CSCs) with
      parallel non-tumorous liver tissues (CD90(+)NTSCs) and elucidate the roles of
      putative target genes in hepatocarcinogenesis. METHODOLOGY/PRINCIPAL FINDINGS:
      CD90(+) cells were sorted respectively from tumor and adjacent non-tumorous human
      liver tissues using fluorescence-activated cell sorting. The amplified RNAs of
      CD90(+) cells from 3 HCC patients were subjected to RNA-Seq analysis. A
      differential gene expression profile was established between CD90(+)CSCs and
      CD90(+)NTSCs, and validated by quantitative real-time PCR (qRT-PCR) on the same
      set of amplified RNAs, and further confirmed in an independent cohort of 12 HCC
      patients. Five hundred genes were differentially expressed (119 up-regulated and
      381 down-regulated genes) between CD90(+)CSCs and CD90(+)NTSCs. Gene ontology
      analysis indicated that the over-expressed genes in CD90(+)CSCs were associated
      with inflammation, drug resistance and lipid metabolism. Among the differentially
      expressed genes, glypican-3 (GPC3), a member of glypican family, was markedly
      elevated in CD90(+)CSCs compared to CD90(+)NTSCs. Immunohistochemistry
      demonstrated that GPC3 was highly expressed in forty-two human liver tumor
      tissues but absent in adjacent non-tumorous liver tissues. Flow cytometry
      indicated that GPC3 was highly expressed in liver CD90(+)CSCs and mature cancer
      cells in liver cancer cell lines and human liver tumor tissues. Furthermore, GPC3
      expression was positively correlated with the number of CD90(+)CSCs in liver
      tumor tissues. CONCLUSIONS/SIGNIFICANCE: The identified genes, such as GPC3 that
      are distinctly expressed in liver CD90(+)CSCs, may be promising gene candidates
      for HCC therapy without inducing damages to normal liver stem cells.

PMID- 22606346
TI  - Increased mast cell density and airway responses to allergic and non-allergic
      stimuli in a sheep model of chronic asthma.
AB  - BACKGROUND: Increased mast cell (MC) density and changes in their distribution in
      airway tissues is thought to contribute significantly to the pathophysiology of
      asthma. However, the time sequence for these changes and how they impact small
      airway function in asthma is not fully understood. The aim of the current study
      was to characterise temporal changes in airway MC density and correlate these
      changes with functional airway responses in sheep chronically challenged with
      house dust mite (HDM) allergen. METHODOLOGY/PRINCIPAL FINDINGS: MC density was
      examined on lung tissue from four spatially separate lung segments of allergic
      sheep which received weekly challenges with HDM allergen for 0, 8, 16 or 24
      weeks. Lung tissue was collected from each segment 7 days following the final
      challenge. The density of tryptase-positive and chymase-positive MCs (MC(T) and
      MC(TC) respectively) was assessed by morphometric analysis of airway sections
      immunohistochemically stained with antibodies against MC tryptase and chymase.
      MC(T) and MC(TC) density was increased in small bronchi following 24 weeks of HDM
      challenges compared with controls (P<0.05). The MC(TC)/MC(T) ratio was
      significantly increased in HDM challenged sheep compared to controls (P<0.05).
      MC(T) and MC(TC) density was inversely correlated with allergen-induced increases
      in peripheral airway resistance after 24 weeks of allergen exposure (P<0.05).
      MC(T) density was also negatively correlated with airway responsiveness after 24
      challenges (P<0.01). CONCLUSIONS: MC(T) and MC(TC) density in the small airways
      correlates with better lung function in this sheep model of chronic asthma.
      Whether this finding indicates that under some conditions mast cells have
      protective activities in asthma, or that other explanations are to be considered
      requires further investigation.

PMID- 22606347
TI  - Influence of corpus callosum damage on cognition and physical disability in
      multiple sclerosis: a multimodal study.
AB  - BACKGROUND: Corpus callosum (CC) is a common target for multiple sclerosis (MS)
      pathology. We investigated the influence of CC damage on physical disability and
      cognitive dysfunction using a multimodal approach. METHODS: Twenty-one relapsing
      remitting MS patients and 13 healthy controls underwent structural MRI and
      diffusion tensor of the CC (fractional anisotropy; mean diffusivity, MD; radial
      diffusivity, RD; axial diffusivity). Interhemisferic transfer of motor inhibition
      was assessed by recording the ipsilateral silent period (iSP) to transcranial
      magnetic stimulation. We evaluated cognitive function using the Brief Repeatable
      Battery and physical disability using the Expanded Disability Status Scale (EDSS)
      and the MS Functional Composite (MSFC) z-score. RESULTS: The iSP latency
      correlated with physical disability scores (r ranged from 0.596 to 0.657, P
      values from 0.004 to 0.001), and with results of visual memory (r = -0.645, P =
      0.002), processing speed (r = -0.51, P = 0.018) and executive cognitive domain
      tests (r = -0.452, P = 0.039). The area of the rostrum correlated with the EDSS
      (r = -0.442, P = 0.045). MD and RD correlated with cognitive performance, mainly
      with results of visual and verbal memory tests (r ranged from -0.446 to -0.546, P
      values from 0.048 to 0.011). The iSP latency correlated with CC area (r = -0.345,
      P = 0.049), volume (r = -0.401, P = 0.002), MD (r = 0.404, P = 0.002) and RD (r =
      0.415, P = 0.016). CONCLUSIONS: We found evidence for structural and
      microstructural CC abnormalities associated with impairment of motor callosal
      inhibitory conduction in MS. CC damage may contribute to cognitive dysfunction
      and in less extent to physical disability likely through a disconnection
      mechanism.

PMID- 22606348
TI  - MicroRNA regulation of human protease genes essential for influenza virus
      replication.
AB  - Influenza A virus causes seasonal epidemics and periodic pandemics threatening
      the health of millions of people each year. Vaccination is an effective strategy
      for reducing morbidity and mortality, and in the absence of drug resistance, the
      efficacy of chemoprophylaxis is comparable to that of vaccines. However, the
      rapid emergence of drug resistance has emphasized the need for new drug targets.
      Knowledge of the host cell components required for influenza replication has been
      an area targeted for disease intervention. In this study, the human protease
      genes required for influenza virus replication were determined and validated
      using RNA interference approaches. The genes validated as critical for influenza
      virus replication were ADAMTS7, CPE, DPP3, MST1, and PRSS12, and pathway analysis
      showed these genes were in global host cell pathways governing inflammation (NF
      kappaB), cAMP/calcium signaling (CRE/CREB), and apoptosis. Analyses of host
      microRNAs predicted to govern expression of these genes showed that eight miRNAs
      regulated gene expression during virus replication. These findings identify
      unique host genes and microRNAs important for influenza replication providing
      potential new targets for disease intervention strategies.

PMID- 22606349
TI  - Interleukin-12p40 modulates human metapneumovirus-induced pulmonary disease in an
      acute mouse model of infection.
AB  - The mechanisms that regulate the host immune response induced by human
      metapneumovirus (hMPV), a newly-recognized member of the Paramyxoviridae family,
      are largely unknown. Cytokines play an important role in modulating inflammatory
      responses during viral infections. IL-12p40, a known important mediator in
      limiting lung inflammation, is induced by hMPV and its production is sustained
      after the resolution phase of infection suggesting that this cytokine plays a
      role in the immune response against hMPV. In this work, we demonstrated that in
      mice deficient in IL-12p40, hMPV infection induced an exacerbated pulmonary
      inflammatory response and mucus production, altered cytokine response, and
      decreased lung function. However, hMPV infection in these mice does not have an
      effect on viral replication. These results identify an important regulatory role
      of IL-12p40 in hMPV infection.

PMID- 22606350
TI  - Vitronectin increases vascular permeability by promoting VE-cadherin
      internalization at cell junctions.
AB  - BACKGROUND: Cross-talk between integrins and cadherins regulates cell function.
      We tested the hypothesis that vitronectin (VN), a multi-functional adhesion
      molecule present in the extracellular matrix and plasma, regulates vascular
      permeability via effects on VE-cadherin, a critical regulator of endothelial cell
      (EC) adhesion. METHODOLOGY/PRINCIPAL FINDINGS: Addition of multimeric VN (mult
      VN) significantly increased VE-cadherin internalization in human umbilical vein
      EC (HUVEC) monolayers. This effect was blocked by the anti-alpha(V)beta(3)
      antibody, pharmacological inhibition and knockdown of Src kinase. In contrast to
      mult VN, monomeric VN did not trigger VE-cadherin internalization. In a modified
      Miles assay, VN deficiency impaired vascular endothelial growth factor-induced
      permeability. Furthermore, ischemia-induced enhancement of vascular permeability,
      expressed as the ratio of FITC-dextran leakage from the circulation into the
      ischemic and non-ischemic hindlimb muscle, was significantly greater in the WT
      mice than in the Vn(-/-) mice. Similarly, ischemia-mediated macrophage
      infiltration was significantly reduced in the Vn(-/-) mice vs. the WT controls.
      We evaluated changes in the multimerization of VN in ischemic tissue in a mouse
      hindlimb ischemia model. VN plays a previously unrecognized role in regulating
      endothelial permeability via conformational- and integrin-dependent effects on VE
      cadherin trafficking. CONCLUSION/SIGNIFICANCE: These results have important
      implications for the regulation of endothelial function and angiogenesis by VN
      under normal and pathological conditions.

PMID- 22606351
TI  - Induction of cellular senescence by doxorubicin is associated with upregulated
      miR-375 and induction of autophagy in K562 cells.
AB  - BACKGROUND: Cellular senescence is a specialized form of growth arrest that is
      generally irreversible. Upregulated p16, p53, and p21 expression and silencing of
      E2F target genes have been characterized to promote the establishment of
      senescence. It can be further aided by the transcriptional repression of
      proliferation-associated genes by the action of HP1gamma, HMGA, and DNMT proteins
      to produce a repressive chromatin environment. Therefore, senescence has been
      suggested to functions as a natural brake for tumor development and plays a
      critical role in tumor suppression and aging. METHODOLOGY/PRINCIPAL FINDINGS: An
      in vitro senescence model has been established by using K562 cells treated with
      50 nM doxorubicin (DOX). Since p53 and p16 are homozygously deleted in the K562
      cells, the DOX-induced senescence in K562 cells ought to be independent of p53
      and p16-pRb pathways. Indeed, no change in the expression of the typical
      senescence-associated premalignant cell markers in the DOX-induced senescent K562
      cells was found. MicroRNA profiling revealed upregulated miR-375 in DOX-induced
      senescent K562 cells. Treatment with miR-375 inhibitor was able to reverse the
      proliferation ability suppressed by DOX (p<0.05) and overexpression of miR-375
      suppressed the normal proliferation of K562 cells. Upregulated miR-375 expression
      was associated with downregulated expression of 14-3-3zeta and SP1 genes.
      Autophagy was also investigated since DOX treatment was able to induce cells
      entering senescence and eventually lead to cell death. Among the 24 human
      autophagy-related genes examined, a 12-fold increase of ATG9B at day 4 and a 20
      fold increase of ATG18 at day 2 after DOX treatment were noted.
      CONCLUSIONS/SIGNIFICANCE: This study has demonstrated that in the absence of p53
      and p16, the induction of senescence by DOX was associated with upregulation of
      miR-375 and autophagy initiation. The anti-proliferative function of miR-375 is
      possibly exerted, at least in part, by targeting 14-3-3zeta and SP1 genes.

PMID- 22606353
TI  - Distributed medical image analysis and diagnosis through crowd-sourced games: a
      malaria case study.
AB  - In this work we investigate whether the innate visual recognition and learning
      capabilities of untrained humans can be used in conducting reliable microscopic
      analysis of biomedical samples toward diagnosis. For this purpose, we designed
      entertaining digital games that are interfaced with artificial learning and
      processing back-ends to demonstrate that in the case of binary medical
      diagnostics decisions (e.g., infected vs. uninfected), with the use of crowd
      sourced games it is possible to approach the accuracy of medical experts in
      making such diagnoses. Specifically, using non-expert gamers we report diagnosis
      of malaria infected red blood cells with an accuracy that is within 1.25% of the
      diagnostics decisions made by a trained medical professional.

PMID- 22606352
TI  - Sphingosine-1-phosphate enhances satellite cell activation in dystrophic muscles
      through a S1PR2/STAT3 signaling pathway.
AB  - Sphingosine-1-phosphate (S1P) activates a widely expressed family of G protein
      coupled receptors, serves as a muscle trophic factor and activates muscle stem
      cells called satellite cells (SCs) through unknown mechanisms. Here we show that
      muscle injury induces dynamic changes in S1P signaling and metabolism in vivo.
      These changes include early and profound induction of the gene encoding the S1P
      biosynthetic enzyme SphK1, followed by induction of the catabolic enzyme
      sphingosine phosphate lyase (SPL) 3 days later. These changes correlate with a
      transient increase in circulating S1P levels after muscle injury. We show a
      specific requirement for SphK1 to support efficient muscle regeneration and SC
      proliferation and differentiation. Mdx mice, which serve as a model for muscular
      dystrophy (MD), were found to be S1P-deficient and exhibited muscle SPL
      upregulation, suggesting that S1P catabolism is enhanced in dystrophic muscle.
      Pharmacological SPL inhibition increased muscle S1P levels, improved mdx muscle
      regeneration and enhanced SC proliferation via S1P receptor 2 (S1PR2)-dependent
      inhibition of Rac1, thereby activating Signal Transducer and Activator of
      Transcription 3 (STAT3), a central player in inflammatory signaling. STAT3
      activation resulted in p21 and p27 downregulation in a S1PR2-dependent fashion in
      myoblasts. Our findings suggest that S1P promotes SC progression through the cell
      cycle by repression of cell cycle inhibitors via S1PR2/STAT3-dependent signaling
      and that SPL inhibition may provide a therapeutic strategy for MD.

PMID- 22606354
TI  - Pph3 dephosphorylation of Rad53 is required for cell recovery from MMS-induced
      DNA damage in Candida albicans.
AB  - The pathogenic fungus Candida albicans switches from yeast growth to filamentous
      growth in response to genotoxic stresses, in which phosphoregulation of the
      checkpoint kinase Rad53 plays a crucial role. Here we report that the Pph3/Psy2
      phosphatase complex, known to be involved in Rad53 dephosphorylation, is required
      for cellular responses to the DNA-damaging agent methyl methanesulfonate (MMS)
      but not the DNA replication inhibitor hydroxyurea (HU) in C. albicans. Deletion
      of either PPH3 or PSY2 resulted in enhanced filamentous growth during MMS
      treatment and continuous filamentous growth even after MMS removal. Moreover,
      during this growth, Rad53 remained hyperphosphorylated, MBF-regulated genes were
      downregulated, and hypha-specific genes were upregulated. We have also identified
      S461 and S545 on Rad53 as potential dephosphorylation sites of Pph3/Psy2 that are
      specifically involved in cellular responses to MMS. Therefore, our studies have
      identified a novel molecular mechanism mediating DNA damage response to MMS in C.
      albicans.

PMID- 22606355
TI  - Dihydrotestosterone ameliorates degeneration in muscle, axons and motoneurons and
      improves motor function in amyotrophic lateral sclerosis model mice.
AB  - Amyotrophic lateral sclerosis (ALS) is a lethal disease characterized by a
      progressive loss of motoneurons. The clinical symptoms include skeletal muscle
      weakness and atrophy, which impairs motor performance and eventually leads to
      respiratory failure. We tested whether dihydrotestosterone (DHT), which has both
      anabolic effects on muscle and neuroprotective effects on axons and motoneurons,
      can ameliorate clinical symptoms in ALS. A silastic tube containing DHT crystals
      was implanted subcutaneously in SOD1-G93A mice at early symptomatic age when
      decreases in body weight and grip-strength were observed as compared to wild-type
      mice. DHT-treated SOD1-G93A mice demonstrated ameliorated muscle atrophy and
      increased body weight, which was associated with stronger grip-strength. DHT
      treatment increased the expression of insulin-like growth factor-1 in muscle,
      which can exert myotrophic as well as neurotrophic effects through retrograde
      transport. DHT treatment attenuated neuromuscular junction denervation, and
      axonal and motoneuron loss. DHT-treated SOD1-G93A mice demonstrated improvement
      in motor behavior as assessed by rota-rod and gait analyses, and an increased
      lifespan. Application of DHT is a relatively simple and non-invasive procedure,
      which may be translated into therapy to improve the quality of life for ALS
      patients.

PMID- 22606356
TI  - Loss of emerin alters myogenic signaling and miRNA expression in mouse myogenic
      progenitors.
AB  - Emerin is an integral membrane protein of the inner nuclear membrane. Mutations
      in emerin cause X-linked Emery-Dreifuss muscular dystrophy (EDMD), a disease
      characterized by skeletal muscle wasting and dilated cardiomyopathy. Current
      evidence suggests the muscle wasting phenotype of EDMD is caused by defective
      myogenic progenitor cell differentiation and impaired muscle regeneration. We
      obtained genome-wide expression data for both mRNA and micro-RNA (miRNA) in
      wildtype and emerin-null mouse myogenic progenitor cells. We report here that
      emerin-null myogenic progenitors exhibit differential expression of multiple
      signaling pathway components required for normal muscle development and
      regeneration. Components of the Wnt, IGF-1, TGF-beta, and Notch signaling
      pathways are misexpressed in emerin-null myogenic progenitors at both the mRNA
      and protein levels. We also report significant perturbations in the expression
      and activation of p38/Mapk14 in emerin-null myogenic progenitors, showing that
      perturbed expression of Wnt, IGF-1, TGF-beta, and Notch signaling components
      disrupts normal downstream myogenic signaling in these cells. Collectively, these
      data support the hypothesis that emerin is essential for proper myogenic
      signaling in myogenic progenitors, which is necessary for myogenic
      differentiation and muscle regeneration.

PMID- 22606357
TI  - Regular exercise or changing diet does not influence aortic valve disease
      progression in LDLR deficient mice.
AB  - BACKGROUND: The development and progression of calcific aortic valve disease
      (CAVD) shares a number of similarities with atherosclerosis. Recently we could
      demonstrate that regular exercise training (ET) as primary prevention prevents
      aortic valve disease in LDL-receptor deficient (LDLR(-/-)) mice. We aimed to
      investigate the impact of exercise training on the progression of CAVD in LDLR(-/
      ) mice in the setting of secondary prevention METHODS AND RESULTS: Sixty-four
      LDLR(-/-) mice were fed with high cholesterol diet to induce aortic valve
      sclerosis. Thereafter the animals were divided into 3 groups: group 1 continuing
      on high cholesterol diet, group 2 continuing with cholesterol diet plus 1 h ET
      per day, group 3 continuing with normal mouse chow. After another 16 weeks the
      animal were sacrificed. Histological analysis of the aortic valve thickness
      demonstrated no significant difference between the three groups (control 98.3+/
      4.5 um, ET 88.2+/-6.6 um, change in diet 87.5+/-4.0). Immunohistochemical
      staining for endothelial cells revealed a disrupted endothelial cell layer to the
      same extend in all groups. Furthermore no difference between the groups was
      evident with respect to the expression of inflammatory, fibroblastic and
      osteoblastic markers. CONCLUSION: Based on the present study we have to conclude
      that once the development of a CAVD is initiated, exercise training or a change
      in diet does not have the potential to attenuate the progress of the CAVD.

PMID- 22606358
TI  - Separate origins of group I introns in two mitochondrial genes of the
      katablepharid Leucocryptos marina.
AB  - Mitochondria are descendants of the endosymbiotic alpha-proteobacterium most
      likely engulfed by the ancestral eukaryotic cells, and the proto-mitochondrial
      genome should have been severely streamlined in terms of both genome size and
      gene repertoire. In addition, mitochondrial (mt) sequence data indicated that
      frequent intron gain/loss events contributed to shaping the modern mt genome
      organizations, resulting in the homologous introns being shared between two
      distantly related mt genomes. Unfortunately, the bulk of mt sequence data
      currently available are of phylogenetically restricted lineages, i.e., metazoans,
      fungi, and land plants, and are insufficient to elucidate the entire picture of
      intron evolution in mt genomes. In this work, we sequenced a 12 kbp-fragment of
      the mt genome of the katablepharid Leucocryptos marina. Among nine protein-coding
      genes included in the mt genome fragment, the genes encoding cytochrome b and
      cytochrome c oxidase subunit I (cob and cox1) were interrupted by group I
      introns. We further identified that the cob and cox1 introns host open reading
      frames for homing endonucleases (HEs) belonging to distantly related
      superfamilies. Phylogenetic analyses recovered an affinity between the HE in the
      Leucocryptos cob intron and two green algal HEs, and that between the HE in the
      Leucocryptos cox1 intron and a fungal HE, suggesting that the Leucocryptos cob
      and cox1 introns possess distinct evolutionary origins. Although the current
      intron (and intronic HE) data are insufficient to infer how the homologous
      introns were distributed to distantly related mt genomes, the results presented
      here successfully expanded the evolutionary dynamism of group I introns in mt
      genomes.

PMID- 22606359
TI  - Temporal dissection of K-ras(G12D) mutant in vitro and in vivo using a
      regulatable K-ras(G12D) mouse allele.
AB  - Animal models which allow the temporal regulation of gene activities are valuable
      for dissecting gene function in tumorigenesis. Here we have constructed a
      conditional inducible estrogen receptor-K-ras(G12D) (ER-K-ras(G12D)) knock-in
      mice allele that allows us to temporally switch on or off the activity of K-ras
      oncogenic mutant through tamoxifen administration. In vitro studies using mice
      embryonic fibroblast (MEF) showed that a dose of tamoxifen at 0.05 uM works
      optimally for activation of ER-K-ras(G12D) independent of the gender status.
      Furthermore, tamoxifen-inducible activation of K-ras(G12D) promotes cell
      proliferation, anchor-independent growth, transformation as well as invasion,
      potentially via activation of downstream MAPK pathway and cell cycle progression.
      Continuous activation of K-ras(G12D) in vivo by tamoxifen treatment is sufficient
      to drive the neoplastic transformation of normal lung epithelial cells in mice.
      Tamoxifen withdrawal after the tumor formation results in apoptosis and tumor
      regression in mouse lungs. Taken together, these data have convincingly
      demonstrated that K-ras mutant is essential for neoplastic transformation and
      this animal model may provide an ideal platform for further detailed
      characterization of the role of K-ras oncogenic mutant during different stages of
      lung tumorigenesis.

PMID- 22606360
TI  - Urate and its transgenic depletion modulate neuronal vulnerability in a cellular
      model of Parkinson's disease.
AB  - Urate is a major antioxidant as well as the enzymatic end product of purine
      metabolism in humans. Higher levels correlate with a reduced risk of developing
      Parkinson's disease (PD) and with a slower rate of PD progression. In this study
      we investigated the effects of modulating intracellular urate concentration on 1
      methyl-4-phenyl-pyridinium (MPP(+))-induced degeneration of dopaminergic neurons
      in cultures of mouse ventral mesencephalon prepared to contain low (neuron
      enriched cultures) or high (neuron-glial cultures) percentage of astrocytes.
      Urate, added to the cultures 24 hours before and during treatment with MPP(+),
      attenuated the loss of dopaminergic neurons in neuron-enriched cultures and fully
      prevented their loss and atrophy in neuron-astrocyte cultures. Exogenous urate
      was found to increase intracellular urate content in cortical neuronal cultures.
      To assess the effect of reducing cellular urate content on MPP(+)-induced
      toxicity, mesencephalic neurons were prepared from mice over-expressing urate
      oxidase (UOx). Transgenic UOx expression decreased endogenous urate content both
      in neurons and astrocytes. Dopaminergic neurons expressing UOx were more
      susceptible to MPP(+) in mesencephalic neuron-enriched cultures and to a greater
      extent in mesencephalic neuron-astrocyte cultures. Our findings correlate
      intracellular urate content in dopaminergic neurons with their toxin resistance
      in a cellular model of PD and suggest a facilitative role for astrocytes in the
      neuroprotective effect of urate.

PMID- 22606361
TI  - Iron status predicts treatment failure and mortality in tuberculosis patients: a
      prospective cohort study from Dar es Salaam, Tanzania.
AB  - BACKGROUND: Experimental data suggest a role for iron in the course of
      tuberculosis (TB) infection, but there is limited evidence on the potential
      effects of iron deficiency or iron overload on the progression of TB disease in
      humans. The aim of the present analysis was to examine the association of iron
      status with the risk of TB progression and death. METHODOLOGY/PRINCIPAL FINDINGS:
      We analyzed plasma samples and data collected as part a randomized micronutrient
      supplementation trial (not including iron) among HIV-infected and HIV-uninfected
      TB patients in Dar es Salaam, Tanzania. We prospectively related baseline plasma
      ferritin concentrations from 705 subjects (362 HIV-infected and 343 HIV
      uninfected) to the risk of treatment failure at one month after initiation, TB
      recurrence and death using binomial and Cox regression analyses. Overall, low
      (plasma ferritin<30 ug/L) and high (plasma ferritin>150 ug/L for women and>200
      ug/L for men) iron status were seen in 9% and 48% of patients, respectively.
      Compared with normal levels, low plasma ferritin predicted an independent
      increased risk of treatment failure overall (adjusted RR = 1.95, 95% CI: 1.07 to
      3.52) and of TB recurrence among HIV-infected patients (adjusted RR = 4.21, 95%
      CI: 1.22 to 14.55). High plasma ferritin, independent of C-reactive protein
      concentrations, was associated with an increased risk of overall mortality
      (adjusted RR = 3.02, 95% CI: 1.95 to 4.67). CONCLUSIONS/SIGNIFICANCE: Both iron
      deficiency and overload exist in TB patients and may contribute to disease
      progression and poor clinical outcomes. Strategies to maintain normal iron status
      in TB patients could be helpful to reduce TB morbidity and mortality.

PMID- 22606362
TI  - Genome-wide gene amplification during differentiation of neural progenitor cells
      in vitro.
AB  - DNA sequence amplification is a phenomenon that occurs predictably at defined
      stages during normal development in some organisms. Developmental gene
      amplification was first described in amphibians during gametogenesis and has not
      yet been described in humans. To date gene amplification in humans is a hallmark
      of many tumors. We used array-CGH (comparative genomic hybridization) and FISH
      (fluorescence in situ hybridization) to discover gene amplifications during in
      vitro differentiation of human neural progenitor cells. Here we report a complex
      gene amplification pattern two and five days after induction of differentiation
      of human neural progenitor cells. We identified several amplified genes in neural
      progenitor cells that are known to be amplified in malignant tumors. There is
      also a striking overlap of amplified chromosomal regions between differentiating
      neural progenitor cells and malignant tumor cells derived from astrocytes. Gene
      amplifications in normal human cells as physiological process has not been
      reported yet and may bear resemblance to developmental gene amplifications in
      amphibians and insects.

PMID- 22606363
TI  - Functional MRI in awake unrestrained dogs.
AB  - Because of dogs' prolonged evolution with humans, many of the canine cognitive
      skills are thought to represent a selection of traits that make dogs particularly
      sensitive to human cues. But how does the dog mind actually work? To develop a
      methodology to answer this question, we trained two dogs to remain motionless for
      the duration required to collect quality fMRI images by using positive
      reinforcement without sedation or physical restraints. The task was designed to
      determine which brain circuits differentially respond to human hand signals
      denoting the presence or absence of a food reward. Head motion within trials was
      less than 1 mm. Consistent with prior reinforcement learning literature, we
      observed caudate activation in both dogs in response to the hand signal denoting
      reward versus no-reward.

PMID- 22606364
TI  - Predicting the DNA sequence dependence of nanopore ion current using atomic
      resolution Brownian dynamics.
AB  - It has become possible to distinguish DNA molecules of different nucleotide
      sequences by measuring ion current passing through a narrow pore containing DNA.
      To assist experimentalists in interpreting the results of such measurements and
      to improve the DNA sequence detection method, we have developed a computational
      approach that has both the atomic-scale accuracy and the computational efficiency
      required to predict DNA sequence-specific differences in the nanopore ion
      current. In our Brownian dynamics method, the interaction between the ions and
      DNA is described by three-dimensional potential of mean force maps determined to
      a 0.03 nm resolution from all-atom molecular dynamics simulations. While this
      atomic-resolution Brownian dynamics method produces results with orders of
      magnitude less computational effort than all-atom molecular dynamics requires, we
      show here that the ion distributions and ion currents predicted by the two
      methods agree. Finally, using our Brownian dynamics method, we find that a small
      change in the sequence of DNA within a pore can cause a large change in the ion
      current, and validate this result with all-atom molecular dynamics.

PMID- 22606365
TI  - Non-iminosugar glucocerebrosidase small molecule chaperones.
AB  - Small molecule chaperones are a promising therapeutic approach for the Lysosomal
      Storage Disorders (LSDs). Here, we report the discovery of a new series of non
      iminosugar glucocerebrosidase inhibitors with chaperone capacity, and describe
      their structure activity relationship (SAR), selectivity, cell activity
      phamacokinetics.

PMID- 22606366
TI  - Anatomy of a microearthquake sequence on an active normal fault.
AB  - The analysis of similar earthquakes, such as events in a seismic sequence, is an
      effective tool with which to monitor and study source processes and to understand
      the mechanical and dynamic states of active fault systems. We are observing
      seismicity that is primarily concentrated in very limited regions along the 1980
      Irpinia earthquake fault zone in Southern Italy, which is a complex system
      characterised by extensional stress regime. These zones of weakness produce
      repeated earthquakes and swarm-like microearthquake sequences, which are
      concentrated in a few specific zones of the fault system. In this study, we
      focused on a sequence that occurred along the main fault segment of the 1980
      Irpinia earthquake to understand its characteristics and its relation to the
      loading-unloading mechanisms of the fault system.

PMID- 22606368
TI  - The Australian paradox.

PMID- 22606367
TI  - Celiac disease, inflammation and oxidative damage: a nutrigenetic approach.
AB  - Celiac disease (CD), a common heritable chronic inflammatory condition of the
      small intestine caused by permanent intolerance to gluten/gliadin (prolamin), is
      characterized by a complex interplay between genetic and environmental factors.
      Developments in proteomics have provided an important contribution to the
      understanding of the biochemical and immunological aspects of the disease and the
      mechanisms involved in toxicity of prolamins. It has been demonstrated that some
      gliadin peptides resistant to complete proteolytic digestion may directly affect
      intestinal cell structure and functions by modulating gene expression and
      oxidative stress. In recent years, the creation of the two research fields
      Nutrigenomics and Nutrigenetics, has enabled the elucidation of some interactions
      between diet, nutrients and genes. Various dietary components including long
      chain omega-3 fatty acids, plant flavonoids, and carotenoids have been
      demonstrated to modulate oxidative stress, gene expression and production of
      inflammatory mediators. Therefore their adoption could preserve intestinal
      barrier integrity, play a protective role against toxicity of gliadin peptides
      and have a role in nutritional therapy of celiac disease.

PMID- 22606369
TI  - Sources and determinants of vitamin D intake in Danish pregnant women.
AB  - Vitamin D deficiency during pregnancy has been associated with the development of
      several adverse health outcomes, e.g., pre-eclampsia, gestational diabetes
      mellitus, preterm delivery, low birth weight, birth length, and bone mineral
      content. The aims of the present study were to estimate the intake and sources of
      vitamin D in Danish pregnant women and to examine potential determinants of
      vitamin D intake of the recommended level (10 ug per day). In 68,447 Danish
      pregnant women the mean +/- SD for vitamin D intake was 9.23 +/- 5.60 ug per day
      (diet: 3.56 +/- 2.05 ug per day, supplements: 5.67 +/- 5.20 ug per day). 67.6% of
      the women reported use of vitamin D supplements but only 36.9% reported use of
      vitamin D supplements of at least 10 ug. Supplements were the primary source of
      vitamin D for the two higher quartiles of total vitamin D intake, with diet being
      the primary source for the two lower quartiles. Determinants of sufficient total
      vitamin D intake were: high maternal age, nulliparity, non-smoking, and filling
      out of the Food Frequency Questionnaire (FFQ) during summer or fall. We propose
      that clinicians encourage vitamin D supplementation among pregnant women, with
      special focus on vulnerable groups such as the young, smokers and multiparous
      women, in order to improve maternal and fetal health both during and after
      pregnancy.

PMID- 22606370
TI  - Disordered eating among preadolescent boys and girls: the relationship with child
      and maternal variables.
AB  - OBJECTIVE: (i) To analyze the eating behaviors and body satisfaction of boys and
      girls and to examine their mothers' perceptions of these two domains; and (ii) to
      evaluate eating problem predictors using child body mass index (BMI), self
      esteem, and body satisfaction as well as maternal BMI, eating problems, and
      satisfaction with their child's body. The participants included 111 children
      (54.1% girls aged between 9 and 12 years old) and their mothers. Assessment
      measures included the Child Eating Attitude Test, the Self-Perception Profile for
      Children, the Eating Disorders Questionnaire, and the Child Eating Behavior
      Questionnaire. Child and maternal measures also included BMI and Collins Figure
      Drawings. RESULTS: (i) No association between child and maternal BMI for either
      sex was found; (ii) no difference was found between boys and girls with regard to
      eating behavior; (iii) most children revealed a preference for an ideal body
      image over their actual body image; (iv) most mothers preferred thinner bodies
      for their children; (v) greater BMI was related to higher body dissatisfaction;
      and (vi) child BMI and dissatisfaction with body image predicted eating
      disturbances in boys, whereas self-esteem, maternal BMI, and eating behavior
      predicted them in girls. DISCUSSION: Maternal eating problems and BMI were
      related to female eating problems only.

PMID- 22606371
TI  - Low glycaemic index dietary interventions in youth with cystic fibrosis: a
      systematic review and discussion of the clinical implications.
AB  - A systematic review was conducted to assess what is known about the effect of low
      glycaemic index (GI) diets on glycaemic control, weight and quality of life in
      youth with cystic fibrosis (CF). Eligibility criteria were systematic reviews,
      randomised and non-randomised trials of low GI dietary interventions in CF.
      Outcomes examined were glycaemic control, quality of life, anthropometry and
      respiratory function. Reference lists were manually searched and experts in the
      field were consulted. Four studies met the eligibility criteria; two were
      excluded because they did not include data on any of the outcomes. The remaining
      two were studies that examined GI secondary to any other intervention: one used
      GI as a factor in enteral feeds and the other incorporated low GI dietary
      education into its treatment methodology. There is insufficient evidence to
      recommend use of low GI diets in CF. Since there is evidence to support use of
      low GI diets in type 1, type 2 and gestational diabetes, low GI diets should be
      tested as an intervention for CF. The potential risks and benefits of a low GI
      diet in CF are discussed.

PMID- 22606373
TI  - Maternal vitamin D status and delivery by cesarean.
AB  - We examined the association of vitamin D deficiency to risk of cesarean delivery
      using prospective data in a cohort of 1153 low income and minority gravidae.
      Circulating maternal 25-hydroxyvitamin D and intact parathyroid hormone were
      measured at entry to care 13.73 +/- 5.6 weeks (mean +/- SD). Intake of vitamin D
      and calcium was assessed at three time points during pregnancy. Using recent
      Institute of Medicine guidelines, 10.8% of the gravidae were at risk of vitamin D
      deficiency, and 23.8% at risk of insufficiency. Maternal 25-hydroxyvitamin D was
      related positively to vitamin D and calcium intakes and negatively to circulating
      concentrations of parathyroid hormone. Risk for cesarean delivery was increased
      significantly for vitamin D deficient women; there was no increased risk for
      gravidae at risk of insufficiency. When specific indications were examined,
      vitamin D deficiency was linked to a 2-fold increased risk of cesarean for
      prolonged labor. Results were the similar when prior guidelines for vitamin D
      deficiency (25(OH)D < 37.5nmol/L) and insufficiency (37.5-80 nmol/L) were
      utilized.

PMID- 22606372
TI  - Alcohol and cardiovascular disease--modulation of vascular cell function.
AB  - Alcohol is a commonly used drug worldwide. Epidemiological studies have
      identified alcohol consumption as a factor that may either positively or
      negatively influence many diseases including cardiovascular disease, certain
      cancers and dementia. Often there seems to be a differential effect of various
      drinking patterns, with frequent moderate consumption of alcohol being salutary
      and binge drinking or chronic abuse being deleterious to one's health. A better
      understanding of the cellular and molecular mechanisms mediating the many effects
      of alcohol consumption is beginning to emerge, as well as a clearer picture as to
      whether these effects are due to the direct actions of alcohol itself, or caused
      in part by its metabolites, e.g., acetaldehyde, or by incidental components
      present in the alcoholic beverage (e.g., polyphenols in red wine). This review
      will discuss evidence to date as to how alcohol (ethanol) might affect
      atherosclerosis that underlies cardiovascular and cerebrovascular disease, and
      the putative mechanisms involved, focusing on vascular endothelial and smooth
      muscle cell effects.

PMID- 22606374
TI  - Plant insecticidal toxins in ecological networks.
AB  - Plant secondary metabolites play a key role in plant-insect interactions, whether
      constitutive or induced, C- or N-based. Anti-herbivore defences against insects
      can act as repellents, deterrents, growth inhibitors or cause direct mortality.
      In turn, insects have evolved a variety of strategies to act against plant
      toxins, e.g., avoidance, excretion, sequestration and degradation of the toxin,
      eventually leading to a co-evolutionary arms race between insects and plants and
      to co-diversification. Anti-herbivore defences also negatively impact mutualistic
      partners, possibly leading to an ecological cost of toxin production. However, in
      other cases toxins can also be used by plants involved in mutualistic
      interactions to exclude inadequate partners and to modify the cost/benefit ratio
      of mutualism to their advantage. When considering the whole community, toxins
      have an effect at many trophic levels. Aposematic insects sequester toxins to
      defend themselves against predators. Depending on the ecological context, toxins
      can either increase insects' vulnerability to parasitoids and entomopathogens or
      protect them, eventually leading to self-medication. We conclude that studying
      the community-level impacts of plant toxins can provide new insights into the
      synthesis between community and evolutionary ecology.

PMID- 22606375
TI  - Immunochemical methods for ochratoxin A detection: a review.
AB  - The safety of food and feed depends to a great deal on quality control. Numerous
      compounds and organisms may contaminate food and feed commodities and thus pose a
      health risk for consumers. The compound of interest in this review is ochratoxin
      A (OTA), a secondary metabolite of the fungi Aspergillus and Penicillium. Due to
      its adverse health effects, detection and quantification are of utmost
      importance. Quality control of food and feed requires extraction and analysis,
      including TLC, HPLC, MS, and immunochemical methods. Each of these methods has
      its advantages and disadvantages. However, with regard to costs and rapidity,
      immunochemical methods have gained much interest in the last decade. In this
      review an introduction to immunochemistry and assay design will be given to
      elucidate the principles. Further, the application of the various formats to the
      detection and quantification of ochratoxin will be described, including the use
      of commercially available kits.

PMID- 22606376
TI  - Mutagenicity of ochratoxin A and its hydroquinone metabolite in the SupF gene of
      the mutation reporter plasmid Ps189.
AB  - Ochratoxin A (OTA) is a mycotoxin that enhances renal tumor formation in the
      outer medulla of male rat kidney. Direct DNA damage and subsequent mutagenicity
      may contribute to these processes. In this study we have determined whether OTA
      in the absence or presence of activated rat liver microsomes (RLM) or redox
      active transition metals (Fe(III) or Cu(II)) causes promutagenic DNA damage in
      the supF gene of the mutation reporter plasmid pS189 replicating in human Ad293
      cells. In addition, we have assessed the mutagenicity of the hydroquinone
      metabolite (OTHQ) of OTA in the absence or presence of cysteine without added
      cofactors. Our results show that oxidation of OTA, either by RLM or by transition
      metal ions, activates OTA to a directly genotoxic mutagen(s). The Fe(III)/OTA
      system was the most potent mutagen in our experimental system, causing a 32-fold
      increase in mutant fraction (MF) above the spontaneous control MF. The Cu(II)/OTA
      system caused a 9-fold increase in MF, while a 6-10-fold increase in MF was
      observed for OTA in the presence of RLM. The OTHQ metabolite is also mutagenic,
      especially in the presence of cysteine, in which a 6-fold increase in MF was
      observed. Our data provide further insight into OTA bioactivation that may
      account for its in vivo mutagenicity in male rat kidney.

PMID- 22606377
TI  - Influence of mycotoxins and a mycotoxin adsorbing agent on the oral
      bioavailability of commonly used antibiotics in pigs.
AB  - It is recognized that mycotoxins can cause a variety of adverse health effects in
      animals, including altered gastrointestinal barrier function. It is the aim of
      the present study to determine whether mycotoxin-contaminated diets can alter the
      oral bioavailability of the antibiotics doxycycline and paromomycin in pigs, and
      whether a mycotoxin adsorbing agent included into diets interacts with those
      antibiotics. Experiments were conducted with pigs utilizing diets that contained
      blank feed, mycotoxin-contaminated feed (T-2 toxin or deoxynivalenol), mycotoxin
      contaminated feed supplemented with a glucomannan mycotoxin binder, or blank feed
      supplemented with mycotoxin binder. Diets with T-2 toxin and binder or
      deoxynivalenol and binder induced increased plasma concentrations of doxycycline
      administered as single bolus in pigs compared to diets containing blank feed.
      These results suggest that complex interactions may occur between mycotoxins,
      mycotoxin binders, and antibiotics which could alter antibiotic bioavailability.
      This could have consequences for animal toxicity, withdrawal time for oral
      antibiotics, or public health.

PMID- 22606378
TI  - Challenges in the Management of HIV-Infected Malnourished Children in Sub-Saharan
      Africa.
AB  - Infection with HIV, and oftentimes coinfection with TB, complicates the care of
      severely malnourished children in sub-Saharan Africa. These superimposed
      infections challenge clinicians faced with a population of malnourished children
      for whose care evidence-based guidelines have not kept up. Even as the care of
      HIV-uninfected malnourished children has improved dramatically with the advent of
      community-based care and even as there are hopeful signs that the HIV epidemic
      may be stabilizing or ameliorating, significant gaps remain in the care of
      malnourished children with HIV. Here we summarize what is currently known, what
      remains unknown, and what remains challenging about how to treat severely
      malnourished children with HIV and TB.

PMID- 22606379
TI  - EMS Stretcher "Misadventures" in a Large, Urban EMS System: A Descriptive
      Analysis of Contributing Factors and Resultant Injuries.
AB  - Purpose. There is a paucity of data regarding EMS stretcher-operation-related
      injuries. This study describes and analyzes characteristics associated with
      undesirable stretcher operations, with or without resultant injury in a large,
      urban EMS agency. Methods. In the study agency, all stretcher-related
      "misadventures" are required to be documented, regardless of whether injury
      results. All stretcher-related reports between July 1, 2009 and June 30, 2010
      were queried in retrospective analysis, avoiding Hawthorne effect in stretcher
      operations. Results. During the year studied, 129,110 patients were transported.
      23 stretcher incidents were reported (0.16 per 1,000 transports). No patient
      injury occurred. Four EMS providers sustained minor injuries. Among contributing
      aspects, the most common involved operations surrounding the stretcher-ambulance
      safety latch, 14/23 (60.9%). From a personnel injury prevention perspective,
      there exists a significant relationship between combative patients and crew
      injury related to stretcher operation, Fisher's exact test 0.048. Conclusions. In
      this large, urban EMS system, the incidence of injury related to stretcher
      operations in the one-year study period is markedly low, with few personnel
      injuries and no patient injuries incurred. Safety for EMS personnel and patients
      could be advanced by educational initiatives that highlight specific events and
      conditions contributing to stretcher-related adverse events.

PMID- 22606380
TI  - The role of transoral robotic surgery in the management of oropharyngeal cancer:
      a review of the literature.
AB  - Background. Transoral robotic surgery (TORS) is an emerging treatment option for
      the treatment of head and neck malignancies, particularly for oropharyngeal
      squamous cell carcinoma (OPSCC). Preliminary studies have demonstrated excellent
      oncologic and functional outcomes that have led to a resurgence of interest in
      the primary surgical management of OPSCC. The aim of the present study was to
      review the evidence base supporting the use of TORS in OPSCC. Methods. Studies
      evaluating the application of TORS in the treatment of head and neck squamous
      cell carcinoma (HNSCC), and more specifically OPSCC, were identified for review.
      Further searches were made of reference lists for complete evaluation of
      minimally invasive surgery (MIS) in treating OPSCC. Results. Seventeen results
      relating to the application of TORS in treatment of OPSCC were identified.
      Further results relating to the role of transoral laser microsurgery (TLM) in
      OPSCC were included for review. Feasibility, oncologic, and functional data is
      summarized and discussed. Discussion. Management strategies for patients with
      OPSCC continue to evolve. Minimally invasive surgical techniques including TORS
      and TLM offer impressive functional and oncologic outcomes particularly for
      patients with early T-classification and low-volume regional metastatic disease.
      Potential exists for treatment deintensification, particularly in patients who
      are HPV positive.

PMID- 22606381
TI  - Inverted takotsubo-like left ventricular dysfunction with pulmonary oedema
      developed after caesarean delivery complicated by massive haemorrhage in a severe
      preeclamptic parturient with a prolonged painful labour.
AB  - Inverted takotsubo cardiomyopathy (TTC), a variant of stress-induced
      cardiomyopathy, features transient myocardial dysfunction characterized by a
      hyperdynamic left ventricular apex and akinesia of the base. Herein, we describe
      a 38-year-old primigravida with severe preeclampsia who had active labour for 4 h
      followed by an emergency caesarean delivery. She developed postpartum haemorrhage
      due to uterine atony complicated by pulmonary oedema, which was managed with
      large-volume infusion and hysterectomy. Her haemodynamic instability was
      associated with cardiac biomarkers indicative of diffuse myocardial injury and
      echocardiographic findings of an "inverted" TTC. The patient was almost fully
      recovered one month later. Our case shows that a reversible inverted TTC may
      result from a prolonged painful labour. TTC should be listed in the differential
      diagnosis of the patient presenting with pulmonary oedema of unknown origin,
      especially in patients with severe preeclampsia.

PMID- 22606382
TI  - Noninvasive Positive Pressure Ventilation against Reperfusion Pulmonary Edema
      following Percutaneous Transluminal Pulmonary Angioplasty.
AB  - A 69-year-old man with chronic thromboembolic pulmonary hypertension (CTEPH) was
      on amblatory oxygen inhalation therapy (3 L/min) and scheduled for percutaneous
      transluminal pulmonary angioplasty (PTPA). The patient's New York Heart
      Association functional status was class III with recent worsening of dyspnea and
      apparent leg edema. Transthoracic echocardiography revealed right ventricular
      enlargement with mean pulmonary artery pressure of 42 mmHg. After PTPA, he was
      complicated with postoperative reperfusion pulmonary edema, and noninvasive
      positive pressure ventilation (NPPV) was applied immediately. Hypoxemia was
      successfully treated with 15 days of NPPV. Although mean pulmonary artery
      pressure was unchanged, his brain natriuretic peptide level decreased from
      preoperative 390.3 to postoperative 44.3 pg/dL. In addition, total pulmonary
      resistance decreased from preoperative 18 to postoperative 9.6 wood unit.m(2).
      The patient was discharged on day 25 with SpO(2) of 95% on 5 L/min of oxygen
      inhalation. Because pulmonary edema is a postsurgical life-threatening
      complication following PTPA, application of NPPV should be considered.

PMID- 22606383
TI  - Laparoscopic splenectomy in a child with moyamoya syndrome, hereditary
      spherocytosis, and interstitial lung disease: a mere coincidence or partnership
      based on genetic similarities.
AB  - A case of moyamoya syndrome and spherocytosis with concurrent interstitial lung
      disease who underwent laparoscopic splenectomy is being reported. A theory
      regarding their coexistence is being forwarded together with their anesthetic
      management. According to our search, this is the fourth case of moyamoya syndrome
      and the first case with an associated interstitial lung disease in a 10-year-old
      child.

PMID- 22606384
TI  - Water-cooled radiofrequency: a neuroablative or a neuromodulatory modality with
      broader applications?
AB  - We report the successful use of water-cooled radiofrequency where more
      traditional forms of neuroablation-conventional and pulsed radiofrequency-had
      failed to achieve adequate pain relief. We also discuss the mechanism of neural
      damage with water cooled radiofrequency and discuss why this technique may have a
      broader role in the management of a wide array of pain syndromes.

PMID- 22606385
TI  - Sudden Tracheal Collapse during EGD and Subsequent Anesthetic Management with
      Dexmedetomidine-Ketamine in a Patient with Achalasia and Tracheomalacia.
AB  - We present a patient who experienced airway obstruction during an elective
      esophagogastroduodenoscopy (EGD) under anesthesia secondary to previously
      undiagnosed tracheomalacia. Physiology of airway obstruction with forced
      breathing maneuvers is discussed along with the potential advantages of
      dexmedetomidine-ketamine sedation for management of patients with achalasia
      undergoing outpatient endoscopic procedures.

PMID- 22606386
TI  - Awake fibreoptic intubation in the sitting position in a patient with a huge
      goitre.
AB  - A 46-year-old woman was anesthetized for total thyroidectomy. The thyroid was
      massive, deviating the trachea to the right and causing attenuation of the
      trachea radiologically. She had symptoms of respiratory obstruction in the supine
      position. Awake FOB-guided intubation was done in sitting position after airway
      topicalisation, and the airway was intubated with difficulty with 7.0 mm cuffed
      orotracheal tube. We describe this case in detail and discuss the significance of
      careful approach to planning and preparation in the management of such a case.

PMID- 22606387
TI  - Delayed airway obstruction after internal jugular venous catheterization in a
      patient with anticoagulant therapy.
AB  - Delayed onset of neck hematoma following central venous catheterization without
      arterial puncture is uncommon. Herein, we present a patient who developed a
      delayed neck hematoma after repeated attempts at right internal jugular venous
      puncture and subsequent enoxaparin administration. Progressive airway obstruction
      occurred on the third day after surgery. Ultrasound examination revealed diffuse
      hematoma of the right neck, and fibreoptic examination of the airway revealed
      pharyngeal edema. After emergent surgical removal of the hematoma, the patient
      was extubated uneventfully.

PMID- 22606388
TI  - The sheared central venous catheter?
AB  - A fractured central venous catheter (CVC) with embolization of the distal
      fragment may lead to life-threatening complications. We had inserted a right
      subclavian CVC in a 68-year-old female which upon a follow-up chest X-ray
      appeared to have been sheared. A guidewire was inserted through the CVC until the
      J-tip was just beyond the tip of the CVC which were then withdrawn as a single
      assembly. We suspected that the tip of the guidewire might have been entrapped in
      the opening of the middle port, which upon withdrawal of the guidewire could have
      led to CVC folding upon itself and shearing.

PMID- 22606389
TI  - Treatment of Fournier's Gangrene with Combination of Vacuum-Assisted Closure
      Therapy, Hyperbaric Oxygen Therapy, and Protective Colostomy.
AB  - Fournier's gangrene is a rare process which affects soft tissue in the genital
      and perirectal area. It can also progress to all different stages of sepsis, and
      abdominal compartment syndrome can be one of its complications. Two patients in
      septic shock due to Fournier gangrene were admitted to the Intensive Care Unit of
      Emergency Department. In both cases, infection started from the scrotum and the
      necrosis quickly involved genitals, perineal, and inguinal regions. Patients were
      treated with surgical debridement, protective colostomy, hyperbaric oxygen
      therapy, and broad-spectrum antibacterial chemotherapy. Vacuum-assisted closure
      (VAC) therapy was applied to the wound with the aim to clean, decontaminate, and
      avoid abdominal compartmental syndrome development. Both patients survived and
      were discharged from Intensive Care Unit after hyperbaric oxygen therapy cycles
      and abdominal closure.

PMID- 22606390
TI  - Importance of Continuous Pulse Oximetry of the Ipsilateral Thumb/Index Finger
      during Transradial Angiography.
AB  - We present a case of a 63-year-old male undergoing attempted basilar artery
      embolization using a right transradial artery approach in which continuous pulse
      oximetry of the ipsilateral thumb uncovered unanticipated hand ischemia during
      the procedure. A preprocedural evaluation using pulse oximetry of the right thumb
      demonstrated normal waveform and maintenance of normal oxygen saturation during
      manual compression of the right radial artery. This normal waveform and oxygen
      saturation was maintained after insertion of a 6Fr sheath into the radial artery.
      After insertion of a 6Fr guiding catheter into the right vertebral artery, near
      complete dampening of the pulse oximetry waveform and precipitous decline in
      oxygen saturation were noted. Examination of the right hand demonstrated poor
      tissue perfusion. Immediate removal of the guiding catheter led to return of a
      normal waveform, oxygen saturation, and tissue perfusion. This case demonstrates
      the importance of continuous, intraprocedural monitoring of oxygenation of the
      ipsilateral hand during transradial angiography in order to avoid unanticipated
      perfusion abnormalities.

PMID- 22606391
TI  - Ultrasonographic guidance and characterization of cryoanalgesic lesions in
      treating a case of refractory sural neuroma.
AB  - The recurrent pain of a neuroma following surgical excision and burial of nerve
      endings can be clinically challenging to manage. Cryoanalgesia in conjunction
      with ultrasound guidance was used successfully to manage this type of pain.
      Furthermore, ultrasound provided visualization of the cryolesions, as well as the
      relationships of the ice ball to the surrounding tissue. Following the completion
      of the freeze cycle, the tissue can be monitored for return to its usual
      morphology during the thaw period.

PMID- 22606392
TI  - Using General Anesthesia plus Muscle Relaxant in a Patient with Spinal Muscular
      Atrophy Type IV: A Case Report.
AB  - Spinal muscular atrophy (SMA) is a rare genetic disease characterized by
      degeneration of spinal cord motor neurons, which results in hypotonia and muscle
      weakness. Patients with type IV SMA often have onset of weakness from adulthood.
      Anesthetic management is often difficult in these patients as a result of muscle
      weakness and hypersensitivity to neuromuscular blocking agents as shown by (Lunn
      and Wang; 2008, Simic; 2008, and Cifuentes-Diaz et al.; 2002). Herein we report a
      case of anesthetic management of a patient with SMA type IV for mammectomy and
      review some other cases of SMA patients receiving different kinds of anesthesia.

PMID- 22606393
TI  - Inadvertent Entrapment of a Central Venous Catheter by a Purse-String Suture
      during Cardiopulmonary Bypass: A Case Report.
AB  - A 65-year-old female patient with severe mitral valve stenosis plus coronary
      artery disease was scheduled for mitral valve replacement and 2-vessel coronary
      artery bypass graft (CABG) surgeries simultaneously. After a successful
      procedure, resistance was met on a CVC withdrawal. During postoperative
      fluoroscopy, fixation of the catheter at the heart was confirmed which
      necessitated reopening the chest, cutting the suture, and removing the catheter.
      When a catheter became hard to withdraw after open heart surgery, we should never
      withdraw it forcefully and blindly. Although rare, one should consider
      inadvertent entrapment of CVC by a suture as the possible cause.

PMID- 22606394
TI  - Unusual Displacement of a Mobilised Dental Bridge during Orotracheal Intubation.
AB  - Dental trauma during tracheal intubation mostly happens in case of poor
      dentition, restricted mouth opening, and/or difficult laryngoscopy. 57-year-old
      man undergoing laparoscopic radiofrequency ablation of unresectable
      hepatocellular carcinoma had his dental work detached at induction of anesthesia.
      Oropharyngeal direct view, manual inspection, fibreoptic nosendoscopy,
      tracheobronchoscopy, and fiberoptic inspection of the esophagus and stomach were
      unsuccessful in locating the dislodged bridge. While other possible exams were
      considered, such as lateral and AP x-ray of head and neck, further meticulous
      manual "sweepings" of the mouth were performed, and by moving the first and
      second fingers below the soft palate deep towards the posterolateral wall of the
      pharynx, feeling consistent with a dental prosthesis was detected in the right
      pharyngeal recess. Only after pulling the palatopharyngeal arch upward was it
      possible to grasp it and extract it out with the aid of a Magill Catheter
      Forceps. Even though the preexisting root and bridge deficits were well reported
      by the consultant dentist, the patient was fully reimbursed. The lack of
      appropriate documentation of the advanced periodontal disease in the anesthesia
      records, no mention of potential risks on anesthesia consent, and insufficient
      protective measures during airway instrumentation reinforced the reimbursement
      claim.

PMID- 22606395
TI  - Anesthetic evaluation and perioperative management in a patient with new onset
      mediastinal mass syndrome presenting for emergency surgery.
AB  - Mediastinal mass syndrome (MMS) is a complex case that poses many challenges to
      the anesthesiologist. The cornerstone of management focuses on the potential
      hemodynamic changes associated with this syndrome. We describe the anesthetic
      management of a patient with a previously undiagnosed mediastinal mass presenting
      for emergency neurosurgical surgery.

PMID- 22606396
TI  - General anaesthesia for laparoscopic cholecystectomy in a patient with the kearns
      sayre syndrome.
AB  - We report a case of a 40-year-old man affected by the Kearns-Sayre syndrome who
      underwent an elective laparoscopic cholecystectomy under general anaesthesia. We
      describe the management of general anaesthesia in this rare myopathy, with
      emphasis on the use of rocuronium as muscle blocking agent. Induction was
      achieved with propofol and fentanyl, and general anaesthesia was maintained with
      fentanyl and sevoflurane/N(2)O/O(2) mixture. The anaesthetic plan proved to be
      safe and effective, and extubation was achieved in the operating theatre. The
      postoperative recovery of the patient was satisfactory and uneventful.

PMID- 22606397
TI  - Laryngeal radiation fibrosis: a case of failed awake flexible fibreoptic
      intubation.
AB  - Awake fibreoptic intubation is accepted as the gold standard for intubation of
      patients with an anticipated difficult airway. Radiation fibrosis may cause
      difficulties during the intubation procedure. We present an unusual severe case
      of radiation induced changes to the larynx, with limited clinical symptoms, that
      caused failure of the fibreoptic intubation technique. A review of the known
      literature on radiation fibrosis and airway management is presented.

PMID- 22606398
TI  - Filgrastim as a rescue therapy for persistent neutropenia in a case of dengue
      hemorrhagic Fever with acute respiratory distress syndrome and myocarditis.
AB  - Pathogenesis of dengue involves suppression of immune system leading to
      development of characteristic presentation of haematological picture of
      thrombocytopenia and leucopenia. Sometimes, this suppression in immune response
      is responsible for deterioration in clinical status of the patient in spite of
      all specific and supportive therapy. Certain drugs like steroids are used for
      rescue therapy in conditions like sepsis. We present a novel use of filgrastim as
      a rescue therapy in a patient with dengue hemorrhagic fever (DHF) with acute
      respiratory distress syndrome (ARDS), myocarditis, and febrile neutropenia and
      not responding to standard management.

PMID- 22606399
TI  - Quality of life following permanent neurological damage after subarachnoid block.
AB  - Introduction. Caesarean section is the commonest operation carried out in females
      of the reproductive age group. Spinal anaesthesia is commonly used for caesarean
      section with its risk. Permanent paralysis of the lower limbs following
      subarachnoid block is a rare complication but can occur even in the best of
      hands. Case Summary. This is a 29-year-old final-year university student now 34
      years old who had emergency caesarean section for cephalopelvic disproportion in
      2005 under spinal anaesthesia in a low-resource setting in a developing country.
      She developed permanent neurological deficit thereafter. She had urinary and
      faecal incontinence for one year. She lost one academic session at her school
      because of long hospital stay and is now confined to a wheel chair. She
      celebrated her daughter's fifth birthday in October, 2010. Although there is
      ability in inability, she is now disabled. Conclusion. It is important for
      clinicians to recognise the complications of subarachnoid block promptly to avoid
      delay in treatment and severe neurological deficits.

PMID- 22606400
TI  - Accidental subcutaneous remifentanil infusion as a cause of delayed awakening
      after craniotomy.
AB  - We report a case of accidental subcutaneous infusion of remifentanil as a cause
      of delayed awakening after a craniotomy.

PMID- 22606401
TI  - Sensitivity to rocuronium-induced neuromuscular block and reversibility with
      sugammadex in a patient with myotonic dystrophy.
AB  - We report a patient with myotonic dystrophy who showed prolonged rocuronium
      induced neuromuscular blockade, although with a fast recovery with sugammadex.
      During general anesthesia with propofol and remifentanil, the times to
      spontaneous recovery of the first twitch (T1) of train of four to 10% of control
      values after an intubating dose of rocuronium 1 mg/kg and an additional dose of
      0.2 mg/kg were 112 min and 62 min, respectively. Despite the high sensitivity to
      rocuronium, sugammadex 2 mg/kg administered at a T1 of 10% safely and effectively
      antagonized rocuronium-induced neuromuscular block in 90 s.

PMID- 22606402
TI  - Administration of anesthesia in a patient with allgrove syndrome.
AB  - The aim of the present paper is to report the anesthesia administration to a
      patient who was planned to undergo Heller myotomy for achalasia. There wasnot
      property in the patient whom allgrove syndrome was excepted any steroid treatment
      in preoperative period. The night before the operation 18 mg of prednisolone was
      administered intravenously. Induction of anesthesia was performed with thiopental
      sodium, vecuronium and fentanyl and the patient received endotracheal intubation.
      Eyes were taped closed and protected with ointment during surgery. Maintenance of
      anesthesia was achieved with 2% sevoflurane concentration in 50% O(2)-50% N(2)O.
      25 mg of prednisolone was infused preoperatively, and intervention with insulin
      treatment was initiated when blood glucose level rose to 18 mmol/L at 2 hours.
      Safe anesthesia can be achieved by observing the preoperative development of
      tracheal aspiration, adrenal insufficiency and, autonomic dysfunction carefully
      and maintaining eye protection.

PMID- 22606403
TI  - The risk of regurgitation and pulmonary aspiration in a patient after gastric
      banding.
AB  - Laparoscopic gastric banding is a popular surgical treatment performed to control
      morbid obesity all over the world. Regurgitation of food material from stomach is
      very common in these patients. Remnants of food material may risk the airway for
      pulmonary aspiration. This case experience shows that despite the extended
      fasting period, airway is not protected from the risk of aspiration. Delayed
      gastric emptying and altered gastroesophageal motility keep the food materials in
      the stomach and precipitate regurgitation. So any such patient should be
      considered as full stomach. Airway manipulation in these patients should be under
      direct laryngoscopic vision and rapid sequence induction with endotracheal
      intubation should be considered as mandatory for general anesthesia.

PMID- 22606404
TI  - Venous air embolism leading to cardiac arrest in an infant with cyanotic
      congenital heart disease.
AB  - Gas emboli, including venous and arterial, are a rare but important complication
      of pediatric cardiac surgery. They have the potential to have devastating
      consequences and require prompt recognition and treatment. We present a case of
      gas embolism occurring in the immediate postoperative period in an infant with
      cyanotic congenital heart disease after palliative cardiac surgery resulting in
      cardiopulmonary arrest. The embolism was diagnosed by visualization of air within
      the vessel creating an airlock and occluding pulmonary blood flow.

PMID- 22606406
TI  - Sympathetic blocks provided sustained pain relief in a patient with refractory
      painful diabetic neuropathy.
AB  - The sympathetic nervous system has been implicated in pain associated with
      painful diabetic neuropathy. However, therapeutic intervention targeted at the
      sympathetic nervous system has not been established. We thus tested the
      hypothesis that sympathetic nerve blocks significantly reduce pain in a patient
      with painful diabetic neuropathy who has failed multiple pharmacological
      treatments. The diagnosis of small fiber sensory neuropathy was based on clinical
      presentations and confirmed by skin biopsies. A series of 9 lumbar sympathetic
      blocks over a 26-month period provided sustained pain relief in his legs.
      Additional thoracic paravertebral blocks further provided control of the pain in
      the trunk which can occasionally be seen in severe diabetic neuropathy cases,
      consequent to extensive involvement of the intercostal nerves. These blocks
      provided sustained and significant pain relief and improvement of quality of life
      over a period of more than two years. We thus provided the first clinical
      evidence supporting the notion that sympathetic nervous system plays a critical
      role in painful diabetic neuropathy and sympathetic blocks can be an effective
      management modality of painful diabetic neuropathy. We concluded that the
      sympathetic nervous system is a valuable therapeutic target of pharmacological
      and interventional modalities of treatments in painful diabetic neuropathy
      patients.

PMID- 22606405
TI  - Anesthetic management of direct laryngoscopy and dilatation of subglottic
      stenosis in a patient with severe myasthenia gravis.
AB  - We describe the anesthetic management of a patient with severe myasthenia gravis
      and tracheal stenosis; the patient was scheduled for direct laryngoscopy and
      dilatation. The combination of myasthenia gravis and tracheal obstruction
      presents several difficulties for anesthetic management. The airway is shared;
      therefore, any complications are also shared by the anesthesiologist and
      bronchoscopists. The potential for respiratory compromise in patients undergoing
      the two procedures requires that anesthesiologists be familiar with the
      underlying disease state, as well as the interaction of anesthetic and
      nonanesthetic drugs in a case involving myasthenia gravis. We reviewed the
      literature and report our experience in this case. There is no strong evidence
      for choosing one approach to general anesthesia over another for bronchoscopy.
      Careful preoperative planning and experience in airway management and jet
      ventilation are crucial to prevent an adverse outcome and obtain favorable
      results.

PMID- 22606407
TI  - Accidental intrathecal injection of tranexamic Acid.
AB  - Tranexamic acid (TXA) is a popular antifibrinolytic drug that is commonly used in
      patients with bleeding disorder. Major morbidities and mortalities have been
      reported following inadvertent intrathecal injection of TXA. In this paper,
      inadvertent intrathecal injection of TXA has resulted from similarities in
      appearance between TXA and heavy bupivacaine 0.5% ampoules. The patient
      experienced severe pain in the back and gluteal region upon injection in
      association with systemic hypertension and tachycardia followed by generalized
      myoclonic seizures and ventricular fibrillation.

PMID- 22606408
TI  - Mounier-kuhn syndrome: anesthetic experience.
AB  - Mounier Kuhn syndrome, or congenital tracheobronchomegaly, is an under diagnosed
      clinical entity with peculiar anatomical and physiological features making
      anesthetic care challenging. A 58-year-old chronic smoker with history of
      recurrent pneumonia and bronchiectasis presented for septoplasty. Thoracic
      imaging revealed a dilated trachea and main bronchi, tracheal and bronchial
      diverticuli, and chronic bronchiectasis with mediastinal lymphadenopathy. An 8.5
      cuffed endotracheal tube (ETT) proved too big for his glottic aperture. An 8.0
      cuffed ETT with wet gauze packing yielding an adequate seal. Postoperative
      continuous positive airway pressure to prevent airway collapse followed awake
      extubation. Anesthetic concerns include grossly enlarged and weakened airways,
      inefficient cough mechanisms, presence of tracheal diverticuli, and post
      operative tracheal collapse. Anesthetic planning includes management of
      endotracheal cuff size. Small size yields air leak and ineffective ventilation.
      Large size may lead to mucosal damage. Tube dislodgement, copious secretions,
      chance of expiratory collapse due to the abnormally dilated and thin airways, and
      post operative monitoring all must be considered.

PMID- 22606409
TI  - Unilateral hemiparesis with thoracic epidural in an adolescent.
AB  - Objective. Unilateral sensory and motor blockade is known to occur with epidural
      anesthesia but is rarely reported in children. The differential diagnosis should
      include the presence of a midline epidural septum. Case Report. We describe a
      case of a 16-year-old adolescent who developed repeated complete unilateral
      extensive epidural sensory and motor blockade with Horner's syndrome after
      thoracic epidural catheter placement. This unusual presentation of complete
      hemibody neural blockade has not been reported in the pediatric population.
      Maneuvers to improve contralateral uniform neural blockade were unsuccessful. An
      epidurogram was performed to ascertain the correct location of the catheter
      within the epidural space and presence of sagittal compartmentalization.
      Conclusion. This case report highlights a less frequently reported reason for
      unilateral sensory and motor blockade with epidural anesthesia in children. The
      presence of a midline epidural septum should be considered in the differential
      diagnosis of unilateral epidural blockade.

PMID- 22606410
TI  - Inability to ventilate after tube exchange postoperative to pneumonectomy.
AB  - We report a case of inability to ventilate a patient after completion of
      pneumonectomy, due to migrated tumor tissue to the contralateral side. This
      represents an unusual complication with a high mortality rate. We have managed to
      find the cause in time and were able to remove the obstructive tissue using
      bronchoscopy.

PMID- 22606411
TI  - Intraoperative pontine infarction: a hidden challenge.
AB  - Apneusis, or apneustic respirations, is characterized by an abnormal breathing
      pattern involving gasping and the inability to fully expire. A loss of gag reflex
      and other cranial nerve deficits are also often accompanied with these
      respiratory changes. In neurological intensive care units (NICUs), these
      respiratory and airway changes are not uncommon and have been well documented
      (Lee et al. 1976). These clinical changes are often associated with pontine
      trauma as it is the core pneumotaxic center in the brain stem. We describe the
      airway management of a patient with an acute, occult pontine infarct status post
      craniectomy and cervical laminectomy for decompression of known Chiari
      malformation in the postanesthesia care unit (PACU).

PMID- 22606412
TI  - Asystole following Reintubation during Suspension Laryngoscopy.
AB  - Transient increase in heart rate and mean arterial pressure commonly occur during
      manipulation of the airway via direct laryngoscopy. This phenomenon is understood
      to be due to a sympathetic nervous system reflex causing an increase in plasma
      catecholamines. Rarely, severe bradycardia and possible asystole can occur
      following laryngoscopy. One previous report described asystole during suspension
      laryngoscopy after uneventful direct laryngoscopy. Here we report a case of
      asystole occurring at the time of reinsertion and cuff inflation of an
      endotracheal tube in a patient who had been hemodynamically stable during initial
      direct laryngoscopy and the ensuing suspension laryngoscopy. The asystole was
      immediately recognized and successful cardiopulmonary resuscitation was performed
      with the patient returning to baseline sinus rhythm. Cardiac arrest following
      laryngoscopy is rare. This case highlights the importance of continued vigilance
      even after the initial manipulations of the airway by both direct laryngoscopy
      and suspension laryngoscopy are to be performed. Identifying patients who may
      benefit from premedication with a vagolytic drug may prevent adversity.
      Preoperative heart rate analysis can identify patients with strong vagal tone.

PMID- 22606414
TI  - Rare Cause of Stricture Esophagus-Sarcoma: A Case Report and Review of the
      literature.
AB  - Adenocarcinoma and squamous cell carcinoma account for the vast majority of
      oesophageal malignancies. Other malignancies known to occur in the oesophagus
      include melanoma, sarcoma, and lymphoma. Among the sarcomas, carcinosarcoma is
      the commonest with both carcinomatous and sarcomatous elements followed by
      leiomyosarcoma of mesenchymal origin. Other sarcomas reported in the literature
      are liposarcoma, synovial sarcoma, myxofibrosarcoma, Ewing's sarcoma,
      granulocytic sarcoma, histiocytic sarcoma, schwannoma rhabdomyosarcoma, and
      epithelioid sarcoma. We report a case of malignant spindle cell tumour of
      oesophagus. Sarcomas of esophagus present as a polypoid exophytic soft tissue
      mass. Our patient presented with a stricture which is a rare presentation.
      Locally aggressive treatment with surgery is beneficial, and local palliative
      treatment including radiotherapy is worthwhile.

PMID- 22606413
TI  - Laparoscopic drainage of a hepatic echinococcal cyst: a case report.
AB  - The Echinococcus granulosus tapeworm causes hepatic echinococcosis. It is endemic
      in the Mediterranean region, Middle East, and South America. Human infection is
      secondary to accidental consumption of ova in feces. Absorption through the bowel
      wall and entrance into the portal circulation leads to liver infection. This case
      involves a 34 y/o Moroccan male with an echinococcal liver cyst. His chief
      complaint was RUQ pain. The patient was treated with albendazole and
      praziquantel. His PMH and PSH was noncontributory. Patient was not on any other
      medications. ROS was otherwise unremarkable. The patient was AF VSS. He was
      tender to palpation in RUQ. Liver function tests were normal. Echinococcal titers
      were positive. CT demonstrated a large cystic lesion in the right lobe of the
      liver measuring 13.5 cm in diameter. The patient underwent successful
      laparoscopic drainage and excision of echinococcal cyst. Final pathology
      demonstrated degenerating parasites (E. granulosus) of echinococcal cyst.

PMID- 22606415
TI  - Self-expandable metal stenting of refractory upper gut corrosive strictures: a
      new role for endoscopy?
AB  - Caustic strictures of the gastrointestinal tract are often difficult to treat,
      since relapses are frequent after medical or endoscopic treatment. Thus, novel
      approaches are needed. We report here our experience with self-expandable
      metallic stents (SEMS) as a new endoscopic approach in three patients with
      corrosive strictures of the upper gastrointestinal tract.

PMID- 22606416
TI  - Retroperitoneal leiomyosarcoma presenting as lower gastrointestinal bleeding: a
      case report and review of the literature.
AB  - We report the first known case of a retroperitoneal leiomyosarcoma that presented
      with an endoscopically defined source of gastrointestinal bleeding in the colon.
      A 68-year-old male with a history of diverticulosis, hypertension, and
      hypercholesterolemia who complained of a 3-month history of abdominal pain,
      nausea, and intermittent hematochezia presented for evaluation of large volume
      hematochezia and lightheadedness. Colonoscopy revealed left-sided diverticulosis
      and rectal varices without stigmata of recent bleed. CT scan showed a 26 * 20 *
      13 cm heterogeneous retroperitoneal mass and multiple hypodense hepatic lesions.
      Liver biopsy revealed leiomyosarcoma. In summary, although surgery is the
      mainstay of treatment, resectability has not improved significantly. Early
      recognition and aggressive surgery are keys to long-term survival.

PMID- 22606417
TI  - Acute pancreatitis complicated with choledochal duct rupture.
AB  - Recurrent acute pancreatitis is a rare clinical entity in childhood with unknown
      incidence (Rosendahl et al., 2007) and often occurring in a familial context.
      Genetic factors such as PRSS1 mutations (cationic trypsinogen gene) can be found
      in some patients. However, many remain idiopathic. The natural history remains
      poorly documented and the most frequent complications reported are pain, exocrine
      pancreatic insufficiency, diabetes mellitus, and pancreatic adenocarcinoma after
      long-standing hereditary pancreatitis. We describe a patient with hereditary
      pancreatitis in whom a mild pancreatitis episode was complicated by a perforation
      of the ductus choledochus.

PMID- 22606418
TI  - Retroperitoneal schwannoma: a rare case.
AB  - Introduction. Schwannomas are quiet rare in the retroperitoneal region. Here, we
      describe an incidentally detected retroperitoneal schwannoma in the abdominal
      computerized tomography (CT) of a patient with acute appendicitis. Case
      Presentation. A 38-year-old woman was admitted to the emergency service with the
      complaints of progressive abdominal pain and nausea for the last 24 hours.
      Abdominal examination was compatible with acute abdomen. Acute appendicitis was
      diagnosed by CT. During CT evaluation, a round shaped soft-tissue mass at the
      retroperitoneal area inferior to the right kidney was detected, The mass was
      resected and histology revealed schwannoma. Conclusion. Rare tumoral lesions with
      benign course such as schwannoma can be detected incidentally.

PMID- 22606419
TI  - Multiseptate gallbladder in an asymptomatic child.
AB  - A one-year-old child being investigated for urinary tract infection was diagnosed
      with a multiseptate gallbladder. The patient remains asymptomatic, and
      investigations demonstrate no associated anomalies. Forty-three cases, including
      13 cases in children were identified in the literature. Their presentation and
      management were reviewed.

PMID- 22606420
TI  - Atypical Clinical and Diagnostic Features in Menetrier's Disease in a Child.
AB  - Menetrier's disease is one of the rarest protein-losing gastropathies in
      childhood. It is characterized clinically by non-specific gastrointestinal
      symptoms and edema, biochemically by hypoalbuminemia, and pathologically by
      enlarged gastric folds. In adults, this disease can be devastating with
      significant morbidity and mortality. In childhood, it is a self-limiting,
      transient and benign illness. Its treatment is largely supportive with total
      parenteral nutrition (TPN) while oral intake is encouraged. Acute onset of
      vomiting in healthy school age children can be initially explained by acute viral
      gastroenteritis. However, persistent vomiting associated with hematemesis and
      severe abdominal pain should warrant further work-up. This case report
      illustrates a self-limiting and rare cause of protein-losing enteropathy called
      Menetrier's disease that presented with several variant clinical features not
      typically described in association with this entity.

PMID- 22606421
TI  - An Early Diagnosis of Gastroepiploic Arterial Aneurysm during a Routine Abdominal
      Ultrasound Study.
AB  - Gastroepiploic arterial aneurysm (GEAA) is a rare condition, but the rupture risk
      is very high. We report the case of a patient with incidental finding of GEAA
      during US examination. The diagnosis was confirmed by a computed tomography and
      an angiographic study. A classic laparotomy with aneurysmectomy has been
      successfully performed.

PMID- 22606422
TI  - Role of Confocal Laser Endomicroscopy in Detection of Residual Barrett's
      Esophagus after Radiofrequency Ablation.
AB  - Endoscopic endoluminal radiofrequency ablation (RFA) is a novel and promising
      modality for Barrett's esophagus (BE) treatment. Actually the only surveillance
      method after the ablation treatment is random biopsies throughout the whole
      treated area. Confocal laser endomicroscopy (CLE) is a new endoscopic imaging
      tool that permits high-resolution microscopic examination of the gastrointestinal
      tract. The technology has garnered increasing attention because of its ability to
      provide real-time "optical" biopsy specimens, with a very high sensitivity and
      specificity. This paper summarize the potential application of CLE in the
      surveillance of the reepithelialization of BE, after endoscopic RFA.

PMID- 22606423
TI  - Granulocytic Sarcoma of the Stomach Presenting as Dysphagia during Pregnancy.
AB  - Granulocytic sarcoma also known as extramedullary myeloid sarcoma or chloroma is
      an uncommon manifestation of leukemia and presents as a deposit of leukemic cells
      outside the bone marrow. We report a case of a twenty-five-year-old pregnant
      woman who presented with progressive dysphagia and recurrent postprandial
      vomiting. Upper GI endoscopy had shown large flat laterally spread nodular
      lesions in the cardia and proximal body of stomach. Biopsies from the gastric
      lesion showed granulocytic sarcoma of the stomach. Concurrent peripheral and bone
      marrow picture was suggestive of acute myeloid leukemia (AML-M4). There is
      limited reported literature on granulocytic sarcoma of the stomach. Concurrent
      gastric granulocytic sarcoma involving cardia and AML in pregnancy has not been
      reported till date.

PMID- 22606424
TI  - Campylobacter fetus Bacteremia Revealed by Cellulitis without Gastrointestinal
      Symptoms in the Context of Acquired Hypogammaglobulinemia: A Report of Three
      Cases.
AB  - Campylobacter fetus bacteremia is rare and occurs mainly in patients with
      immunosuppression. This infection, which often involves secondary localizations
      has already been reported in some primary humoral immune deficiencies. We
      describe three cases of severe infection due to C. fetus with cellulitis at
      presentation, but without any gastrointestinal symptoms, occurring in patients
      with acquired hypogammaglobulinemia.

PMID- 22606425
TI  - An unusual case of obscure gastrointestinal bleeding in a patient with coeliac
      disease.
AB  - This paper describes the journey of a patient with coeliac disease who presented
      with overt obscure gastrointestinal bleeding. Upper and lower gastrointestinal
      endoscopy did not reveal a source of bleeding, but an abdominal CT scan detected
      abnormal lymphadenopathy and a wireless capsule endoscopy diagnosed a jejunal
      tumour, which was surgically removed. Gastrointestinal bleeding is rare in celiac
      disease. Malignant tumours of the small intestine are generally uncommon, but
      celiac disease represents a significant risk factor. Wireless capsule endoscopy
      has been a useful tool to investigate patients with obscure gastrointestinal
      bleeding.

PMID- 22606426
TI  - Two Cases of Helicobacter pylori-Negative Gastric Outlet Obstruction in Children.
AB  - Gastric outlet obstruction (GOO) in children is most commonly caused by
      idiopathic hypertrophic pyloric stenosis. Prior to proton pump inhibitors and H2
      blockers, peptic ulcer disease (PUD) secondary to H. pylori was a cause of GOO.
      Both patients presented with a history of weight loss, vomiting, and abdominal
      pain. Their diagnosis of PUD and GOO was made by EGD and UGI. H. pylori testing
      was negative for both on multiple occasions but still received H. pylori
      eradication therapy. Patient 1 after failing pharmaceutical management underwent
      surgery for definitive treatment. Patient 2 underwent six therapeutic pyloric
      dilations before undergoing surgery as definitive treatment. These cases suggest
      that GOO secondary to PUD occurs in the absence of H. pylori infection and
      surgical management can provide definitive therapy.

PMID- 22606427
TI  - Arsenic-induced pancreatitis.
AB  - The introduction of all-trans retinoic acid (ATRA) and arsenic trioxide has
      brought about tremendous advancement in the treatment of acute promyelocytic
      myelogenous leukemia (APML). In most instances, the benefits of these treatments
      outweigh the risks associated with their respective safety profiles. Although
      acute pancreatitis is not commonly associated with arsenic toxicity, it should be
      considered as a possible side effect. We report a case of arsenic-induced
      pancreatitis in a patient with APML.

PMID- 22606428
TI  - Hepatobiliary cystadenoma revealed by a jaundice: a case report.
AB  - Introduction. Hepatobiliary cystadenomas are rare benign cystic tumors and have a
      potential for recurrence and malignant transformation. The diagnosis may be very
      difficult because of absence of typical imaging feature in some cases. Case
      Presentation. In this paper, the authors discuss a 57-year-old woman who
      presented a jaundice related to hepatobiliary cystadenoma. Biological and
      radiological examinations have led to surgery, and the diagnosis is made after a
      histological examination of surgical specimens. Conclusion. This observation
      illustrates a hepatobiliary cystadenoma revealed by jaundice. Histology
      examination contributed to diagnosis. The authors discussed the mechanisms of
      biliary obstruction and differential diagnoses through a review of the
      literature.

PMID- 22606429
TI  - Postoperative Bowel Perforation due to Heterotopic Ossification (Myositis
      Ossificans Traumatica): A Case Report and Review of the Literature.
AB  - Heterotopic ossification (HO) is the ectopic development of normal bone within
      soft tissue that can occur after traumatic injury. It is uncommon and may be
      missed or misdiagnosed, which can lead to complications. We report the case of an
      84-year-old male with a previous history of a laparotomy who underwent resection
      of an intra-abdominal tumor through a midline incision. On postoperative day six,
      the patient was taken to the operating room, as succus was draining from the
      incision. Upon re-exploration, sharp bone-like material was found in the wound
      directly adjacent to an enterotomy. Pathology confirmed mature lamellar bone and
      the diagnosis of HO. This is the first report of postoperative intestinal
      perforation secondary to HO in a midline wound. We report this case to encourage
      accurate reporting of HO and its morbidity and complications for the benefit of
      appropriate surgical planning and epidemiologic tracking of outcomes.

PMID- 22606430
TI  - Splenic artery aneurysm presenting as extrahepatic portal vein obstruction: a
      case report.
AB  - Splenic artery aneurysms are the most common visceral aneurysm occuring
      predominantly in females. They are usually asymptomatic, and the symptomatic
      presentation includes chronic abdominal pain of varied severity or an acute
      rupture with hypotension. Splenic artery aneurysm causing extrahepatic portal
      hypertension is very rare and is due to splenic vein thrombosis that develops
      secondary to compression by the aneurysm. We report one such rare presentation of
      splenic artery aneurysms in a pregnant female with the features of EHPVO
      (variceal bleed, hypersplenism) treated by splenectomy along with excision of the
      aneurysm.

PMID- 22606431
TI  - Severe hemobilia from hepatic artery pseudoaneurysm.
AB  - Background. Hemobilia is a rare, jeopardizing complication of laparoscopic
      cholecystectomy coming upon usually within 4 weeks after surgery. The first-line
      management is angiographic coil embolization of hepatic arteries, which is
      successful in the majority of bleedings: in a minority of cases, a second
      embolization or even laparotomy is needed. Case Presentation. We describe the
      case history of a patient in which laparoscopic cholecystectomy was complicated 3
      weeks later by massive hemobilia. The cause of haemorrhage was a pseudoaneurysm
      of a right hepatic artery branching off the superior mesenteric artery; this
      complication was successfully managed by one-stage angiographic embolization with
      full recovery of the patient.

PMID- 22606432
TI  - A case report of a metastatic gastrointestinal stromal tumor occurring in femur.
AB  - Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms that most
      commonly affect the stomach or small intestine, but can occur anywhere throughout
      the gastrointestinal tract. To the best of our knowledge, few cases have been
      reported in the literature about the femur metastasis of GIST. This paper
      describes a metastasis of a gastrointestinal stromal tumour (GIST) to the femur
      in a 62-year-old male, 2 years after treatment for a gastric primary. There were
      no signs of tumor recurrence at followup after 12 mo. This case suggests that the
      femur can be a potential metastatic site of GIST.

PMID- 22606433
TI  - Nodular regenerative hyperplasia and portal hypertension in a patient with
      coeliac disease.
AB  - Nodular regenerative hyperplasia (NRH) of the liver is often associated with
      rheumatologic or lymphoproliferative disorders and a cause of portal hypertension
      in some patients. We report the case of a 71-year-old patient with celiac disease
      and unexplained portal hypertension. Biopsy of the liver revealed NRH as the
      underlying cause. The patient did not suffer from an autoimmune, rheumatologic or
      lymphoproliferative disease. A thrombophilic disorder that might cause NRH was
      ruled out. Celiac disease is often associated with mild elevation of liver
      enzymes and steatosis of the liver, but the association with NRH was described in
      only a few patients. We discuss the possible relationship of celiac disease and
      NRH.

PMID- 22606434
TI  - Mucosa-associated lymphoid tissue lymphoma of the lacrimal gland: sustained
      remission after eradication of helicobacter pylori infection.
AB  - Mucosa-associated lymphoid tissue (MALT) lymphoma is the third most common non
      Hodgkin lymphoma, and it is strongly associated with helicobacter pylori
      infection of the stomach. MALT lymphoma of the lacrimal gland usually presents as
      a localized disease process in extranodal tissues. The treatment options of MALT
      lymphoma of the lacrimal gland chiefly include radiation of the tumor,
      chemotherapy, surgical removal, or a combination of these strategies. We report a
      case of localized MALT lymphoma of the lacrimal gland, with prolonged sustained
      remission after eradication of gastric Helicobacter pylori (H. Pylori) infection.
      He sustains in remission of lacrimal MALT lymphoma for four years without
      chemotherapy or radiotherapy.

PMID- 22606435
TI  - Gastric antral web in a 103-year-old patient.

PMID- 22606436
TI  - A case of small bowel obstruction caused by bezoars diagnosed with double balloon
      enteroscopy.
AB  - Primary small bowel bezoars are rare and cause acute abdomen due to small bowel
      obstruction (SBO). A 69-year-old Japanese man presented with epigastric pain
      associated with fullness. Physical examination of the abdomen showed no marked
      signs of peritoneal irritation. An erect X-ray film of the abdomen showed small
      bowel obstruction. Computed tomography (CT) showed a dilated small bowel loop
      proximal to the site of the obstruction. Retrograde double balloon enteroscopy
      (DBE) was performed and showed yellow, hard bezoars blocking the distal ileum. At
      surgery, a bezoar was found impacted in the distal ileum, and enterotomy with
      extraction was performed. After 9 days, the patient was discharged from our
      hospital in satisfactory condition. DBE also appears to be a safe and useful
      diagnostic tool in patients with SBO, and the findings of DBE influence the
      strategy of therapy in patients in whom the cause of SBO could not be determined
      by conventional radiography.

PMID- 22606438
TI  - Severe diarrhea in a 4-month-old baby girl with acute gastroenteritis: a case
      report and review of the literature.
AB  - A 4.5-month-old baby girl presented to hospital with a 2-day history of watery
      diarrhea and fever. Rehydration and electrolytic balance were restored with
      intravenous fluid therapy followed by oral rehydration solution but diarrhea did
      not improve by the fourth day of hospitalization despite treatment with a
      probiotic. The patient was next treated with gelatin tannate, a medical device
      recently marketed in Europe to control and reduce the symptoms of diarrhea in
      infants, children, and adults. The child's diarrhea improved considerably within
      the first twelve hours and resolved completely within three days. Gelatin tannate
      might be considered as a useful treatment complementary to oral rehydration
      solution for the treatment of diarrhea in infants with rotavirus gastroenteritis.

PMID- 22606437
TI  - Unexplained findings of kayser-fleischer-like rings in a patient with cryptogenic
      cirrhosis.
AB  - Cryptogenic cirrhosis (CC) is defined as cirrhosis occurring in an individual
      without an identifiable cause of liver disease, such as excessive alcohol
      consumption, viral hepatitis infection, hemochromatosis, autoimmune hepatitis,
      primary biliary cirrhosis, primary sclerosing cholangitis, chronic intake of
      medications that could induce cirrhosis, alpha-1-antitrypsin deficiency, Wilson's
      disease, or any other rare cause of cirrhosis according to the clinical context.
      Cryptogenic cirrhosis is a common cause of liver-related morbidity and mortality
      in the United States. Nonalcoholic fatty liver disease is now recognized as the
      most common cause of cryptogenic cirrhosis. A biopsy specimen is also important
      for detecting histological advanced disease, which may be clinically silent and
      undetected by liver-related tests or diagnostic imaging. We are presenting an
      unusual case of a patient with cryptogenic cirrhosis found to have Kayser
      Fleischer-like rings without evidence of Wilson's disease.

PMID- 22606439
TI  - Local recurrence of breast cancer 52 years after halsted mastectomy: is there a
      role for more aggressive ipsilateral surveillance?
AB  - We present the longest reported case of breast cancer recurrence, 52 years after
      initial diagnosis, in a patient initially treated with Halsted mastectomy.
      Observation and palpation of the chest wall resulted in late presentation, and
      this patient went on to demonstrate metastatic disease. Current surveillance
      guidelines lack specific recommendations regarding monitoring of the ipsilateral
      chest wall. In addition, the growing utilization of breast reconstruction poses
      an additional challenge to surveillance strategies of the ipsilateral breast.
      However, the emergence of MRI may present a new opportunity to identify
      ipsilateral recurrence. The changing landscape of breast cancer therapy warrants
      guidance from groups of national import such as ASCO, in the surveillance of
      breast cancer patients.

PMID- 22606440
TI  - Recurrent PET FDG Uptake after Sequential Chemotherapy and Radiation Therapy for
      DLBCL of the Tibia: A Case Report and Review of the Literature.
AB  - The aim of this paper is to report on the challenges associated with identifying
      disease recurrence following combined modality therapy (CMT) for primary lymphoma
      of the tibia in which an intramedullary nail has been placed. A patient with
      primary bone lymphoma (PBL) was treated with CMT (chemotherapy and radiation
      therapy). After a complete response, he has been followed for eighteen months by
      physical exam and radiographic imaging. Despite persistent increased tracer
      accumulation at the original site, he has no proven recurrence. Literature review
      showed a small number of retrospective, single institution reviews detailing
      clinical experience and expected outcome in patients treated with PBL limited to
      one bony site of disease. PBL presents a treatment challenge, particularly when a
      weight-bearing long bone is diffusely involved and followup is complicated after
      placement of stabilizing hardware. Close coordination of the oncology team and
      diagnostic radiology is required to ensure optimal outcome.

PMID- 22606441
TI  - An unusual presentation of desmoplastic small round cell tumour of the abdomen:
      morphological, immunohistochemical, ultrastructural, and molecular studies.
AB  - Desmoplastic small round cell tumour (DSRCT) is an aggressive and a rare
      neoplasm. We report on a 34-year-old male who had abdominal discomfort with a
      large intraperitoneal mass. Histological examination of the tumour biopsy
      revealed sheets of small round cells. The cells were positive with vimentin and
      desmin (with occasional dot positivity) and negative for WT1 and CD 99 with
      immunohistochemistry. Cytogenetics showed a translocation disrupting the EWSR 1
      gene on 22 q 12 consistent with DSRCT. Electron microscopic examination showed
      sparse cytoplasmic organelles. The patient succumbed 34 months from disease
      presentation after multiple chemotherapies and thereafter radiotherapy. In
      summary, our case exemplifies that it is crucial to combine clinical,
      histological, and molecular aspects in diagnosing DSRCT especially when
      characteristic dot positivity with desmin is weak along with deficient marking of
      WT1 and CD99 by immunohistochemistry. Histology was also less clear than
      published examples of this entity with a poor desmoplastic response. A
      multidisciplinary approach including early referral to specialised centres is
      recommended in these cases as tertiary referral centres will be required to
      substantiate the diagnosis.

PMID- 22606442
TI  - Unusual CT and MR Imaging Characteristics of Splenic Lymphoma.
AB  - Lymphoma is the most common malignancy of the spleen. The imaging features of
      splenic lymphoma are nonspecific and mostly lymphomas present as a diffusely
      enlarged spleen. Focal lesions are described but remain of low density or
      intensity on CT or MRI, respectively. We describe a histologically proven case of
      splenic lymphoma that showed an atypical hyperdense/hyperenhancing appearance on
      imaging suspicious for a vascular pathology. To the best of our knowledge and
      based on review of English literature, such an appearance of splenic lymphoma is
      extremely unusual and rare.

PMID- 22606443
TI  - Adrenal Failure due to Adrenal Metastasis of Lung Cancer: A Case Report.
AB  - We report a case of a patient with adrenal failure due to bilateral adrenal
      metastasis of lung cancer. This is a rare presentation of lung cancer. We review
      the differential diagnosis of weight loss and how to make diagnosis of adrenal
      insufficiency.

PMID- 22606444
TI  - (18)FDG-PET at 1-Month Intervals Is a Better Predictive Marker for GISTs That Are
      Difficult to Be Diagnosed Histopathologically: A Case Report.
AB  - Imatinib mesylate is a tyrosine kinase inhibitor of c-KIT and PDGFRA. Imatinib
      mesylate is an effective drug that can be used as a first-choice agent for
      treatment of GISTs. Prior to treatment, molecular diagnosis of c-KIT or PDGFRA is
      necessary; however, in some types of GISTs, it is impossible to obtain a
      sufficient amount of specimen for diagnosis. An inoperable or marginally
      resectable GIST in a 79-year-old female was difficult to be diagnosed at a
      molecular pathological level, and hence, exploratory treatment was initiated
      using imatinib combined with (18)FDG-PET evaluation at 1-month intervals. PET
      imaging indicated a positive response, and so we continued imatinib treatment in
      an NAC setting for 4 months. As a result, curative resection of the entire tumor
      was successfully performed with organ preservation and minimally invasive
      surgery. (18)FDG-PET evaluation at 1-month intervals is beneficial for GISTs that
      are difficult to be diagnosed histopathologically.

PMID- 22606445
TI  - Subcutaneous Panniculitis-Like T-Cell Lymphoma (SPTL) in a Child with Spontaneous
      Resolution.
AB  - Subcutaneous panniculitis-like T-cell lymphomas (SPTLs) alpha/beta are rare in
      childhood. The present report refers to a case of a 7-year-old male child
      presenting an extensive skin lesion that began when he was 5 years of age. Two
      biopsies were evaluated using the CD3, CD4, CD8, CD56, betaF1, and TIA markers. A
      dense infiltrate of CD3+, CD4-, CD8+, CD56-, betaF1+, and TIA+ pleomorphic
      lymphocytes was found in the subcutis. The previous biopsy showed cytophagic
      histiocytic panniculitis with a small focus on CD8+ and betaF1+ malignant cells.
      The lesion regressed spontaneously. This case shows that prognosis may be
      excellent in SPTL (alpha/beta). On the other hand, it also serves as an alert
      that a biopsy performed in an area of cytophagic panniculitis may lead to
      misdiagnosis.

PMID- 22606446
TI  - Advanced epithelioid malignant peripheral nerve sheath tumor showing complete
      response to combined surgery and chemotherapy: a case report.
AB  - Malignant peripheral nerve sheath tumor (MPNST) is a rare high-grade soft tissue
      sarcoma. The epithelioid variant accounts for 5% or less of MPNSTs; the clinical
      behavior of this variant is unclear. Reports of approximately 40 cases are
      available in the English literature; however, most reports addressed
      clinicopathological features rather than therapeutic procedures or clinical
      courses. We describe a case of a 62-year-old male with an epithelioid MPNST of
      the left foot. Multiple lung metastases developed after radical surgery on the
      primary lesion. The response to adjuvant chemotherapy including doxorubicin and
      ifosfamide was favorable, and thoracoscopic resection was subsequently performed
      on the remaining three metastases. No evidence of recurrence or metastasis was
      observed at the 12-month followup after the first operation. Further followup and
      chemotherapy may be required.

PMID- 22606447
TI  - A Case of an Unusually Aggressive Cutaneous Anaplastic Large T-Cell Lymphoma in
      an HIV Patient Treated with CHOP.
AB  - Anaplastic large cell lymphoma (ALCL) is the second most common malignancy of T
      cell phenotype. This case report describes an unusual rapidly progressing
      cutaneous anaplastic large T-cell lymphoma in an HIV patient. Our patient is a
      twenty-year-old African American male with perinatally acquired HIV who presented
      with a 2 * 2 centimeter necrotic lesion in the right 1st toe; however, 2-3 weeks
      later multiple smaller lesions appeared on the anterior aspect of the right foot,
      ankle, and thigh. Biopsy showed cells strongly positive for CD3 and CD30 and
      negative for CD56 and the ALK gene product. CT of the chest, abdomen, and pelvis
      was negative for extracutaneous involvement favoring cutaneous ALCL. Patient was
      treated with 6 cycles of CHOP (cyclophosphamide, hydroxydaunorubicin,
      vincristine, and prednisone) chemotherapy and went into complete remission. Due
      to the aggressive course that this malignancy follows in HIV patients we suggest
      prompt treatment with systemic therapy.

PMID- 22606448
TI  - Giant merkel cell carcinoma masquerading as a benign cyst on the buttock of an
      african american man.
AB  - We report a case of a 60-year-old African American man who presented with a 4
      year history of a previously asymptomatic, recently enlarging nodule on his left
      buttock, which was initially presumed to be an epidermoid cyst. Physical
      examination revealed a large, fixed, subcutaneous tumor, and a biopsy revealed
      merkel cell carcinoma. Immunohistochemical staining was positive for pankeratin,
      CAM 5.2, synaptophysin, and CD56 and negative for CK7, CK20, TTF-1, chromogranin,
      CD3, CD20, CD57, MART1, and HMB 45. The patient underwent wide local excision of
      the lesion with removal of the fascia overlying the gluteus and full body
      positron emission tomography (PET) and was found to have Stage IIb disease. He
      subsequently received adjuvant radiotherapy limited to the tumor bed at a dose of
      60 gray.

PMID- 22606449
TI  - Metachronous anal canal and prostate cancers with simultaneous definitive
      therapy: a case report and review of the literature.
AB  - Anal canal cancer is rare, accounting for only 1.3% of all gastrointestinal tract
      malignancies. Prostate cancer incidence is much higher and accounts for 27.6% of
      all malignancies in men. Treatment guidelines for anal cancer involve
      radiotherapy to the primary site and draining lymphatics while treatment for
      prostate cancer can also include pelvic radiotherapy. The literature is silent on
      the optimum course of action when these two malignancies are found synchronously
      or metachronously. Herein, we report a case of a patient diagnosed with
      intermediate risk prostate cancer who, prior to definitive therapy for this first
      malignancy, was also diagnosed with anal canal cancer. We conclude that a
      simultaneous approach with radiation therapy and chemotherapy with subsequent
      boost to the prostate is recommended. Screening for synchronous prostate cancer
      in male anal canal cancer patients is probably indicated and may preclude
      suboptimal treatment for a second occult primary.

PMID- 22606450
TI  - Primary small cell carcinoma of the larynx: report of a rare tumor.
AB  - Primary small cell carcinoma of larynx is a rare tumor representing less than
      0.5% of all laryngeal cancers. This is one of the most lethal of all malignancies
      associated with frequent early widespread metastases and dismal prognosis. We
      report a case of a 60-year-old patient with small cell carcinoma of the
      subglottic larynx, who presented with hepatic metastasis.

PMID- 22606451
TI  - The inside mystery of jejunal gastrointestinal stromal tumor: a rare case report
      and review of the literature.
AB  - Gastrointestinal stromal tumors (GISTs) are malignant and rare form of soft
      tissue sarcoma of the digestive tract. The incidence of gastrointestinal stromal
      tumors is very low Kramer et al. 2005 Jejunal GISTs are extremely rare. Here we
      present a rare case of jejunal GIST with unusually large size at presentation.
      The patient presented with severe abdomen pain, exophytic growth, and dimorphic
      anemia. Surgical resection of the tumor was carried out, and operative findings
      revealed a 15 * 10 cm growth, arising from serosal surface of jejunum, at the
      antimesenteric surface. Diagnosis in this case was made by subjecting the
      resected specimen to immunohistochemical analysis. In view of large size of the
      resected tumor, and high-risk histopathological features, imatinib mesylate 400
      mg once daily was given as adjuvant chemotherapy. Patient is asymptomatic without
      any evidence of tumor recurrence after six months of postoperative followup.
      Imatinib as such is recommended in metastatic, residual or recurrent cases of
      GISTs or which are surgically not removable; however, recent recommendations
      suggests the use of imatinib mesylate after radical surgery in high-risk cases,
      because it has shown a significant decrease in the recurrence rate, and the Food
      and Drug Administration (FDA) has also approved the use of imatinib as adjuvant
      therapy after complete resection of localized, primary GIST.

PMID- 22606452
TI  - Arterial emboli complicating Cisplatin therapy.
AB  - We report three cases of arterial emboli in patients with lung cancer treated
      with cisplatin chemotherapy. All three patients were managed without surgical
      intervention but subsequent oncological treatment was complicated by the sequelae
      of arterial emboli. We discuss the issues surrounding these patients and the
      importance of identifying patients at risk of arterial embolic phenomena with
      cisplatin treatment.

PMID- 22606453
TI  - Atypical neurofibroma and osteosclerotic metastasis.
AB  - 35-year-old male presented with multiple swellings in left leg, headache,
      weakness of limbs for 4 months, and blurring of vision for the last 15 days. On
      examination, he was pale, cachexic with generalized lymphadenopathy and lower
      motor neuron type weakness of limbs sparing right upper limb. Blood
      investigations showed anemia with high alkaline phosphatase. Chest radiograph
      revealed osteosclerotic metastatic lesion in humerus. Biopsy of leg lesion
      revealed atypical neurofibroma. Computed tomography (CT) of thorax revealed
      osteoblastic metastasis. Bone marrow aspiration showed cells with round to oval
      nuclei, fine granular chromatin with large central prominent nucleoli and
      eosinophilic cytoplasm with acini formation. Magnetic resonance imaging (MRI) of
      brain and spinal cord defined metastatic leptomeningeal deposits. Cerebrospinal
      fluid (CSF) cytology was positive for malignant cells. Gastroscopy showed an
      ulceroinfiltrative growth from stomach which on histopathology revealed diffuse
      adenocarcinoma. Palliative treatment was given with intrathecal methotrexate and
      systemic corticosteroid with chemotherapy. Patient's symptom improved
      drastically, but we lost him to followup.

PMID- 22606454
TI  - A malignant granular cell tumor excised with mohs micrographic surgery.
AB  - Malignant granular cell tumors are extremely rare, aggressive neoplasms
      displaying rapid growth and frequent associated metastatic disease. Excision and
      evaluation for metastatic disease are mandatory. We present a 54-year-old patient
      with a malignant granular cell tumor, treated with Mohs micrographic surgery.
      Cutaneous granular cell tumors are uncommon neoplasms, likely of perineural
      origin. Most follow a benign and uneventful course, with wide local excision
      being the treatment of choice (Enzinger, 1988). The malignant granular cell tumor
      is an extremely rare, aggressive variant, which provides a diagnostic challenge
      and management dilemma, especially with early presentation when it may be
      mistaken for other entities. There is also controversy regarding surgical
      management and follow-up of both benign and malignant granular cell tumors.

PMID- 22606455
TI  - The great mimicker: zona zoster at the mastectomy site causing contralateral
      intramammary lymph node enlargement.
AB  - Zona zoster is rarely observed in patients with malignancy; when present, it
      follows a dermatomal fashion. Involvement of widely separated regions is very
      rare. Hereby, zona zoster causing enlarged intramammary lymph nodes (IMLN) in the
      opposite breast is reported for the first time in literature. The masses were
      hypoechoic on US with no hilum and hypervascular on color Doppler US. MRI showed
      hypointense masses with type 3 time-intensity curve and adjacent vessel sign. The
      complete regression of the nodes after the antiviral therapy confirmed the
      diagnosis. In breast cancer patients, IMLN enlargements may mimic breast cancer
      metastasis, and zona zoster infection of the mastectomy site may present with
      contralateral IMLN enlargement due to altered lymphatic drainage. When breast US
      is not sufficient for the differential diagnosis, breast MRI may warrant proper
      diagnosis, and prevent unnecessary biopsies. Antiviral treatment with followup
      would be sufficient for management.

PMID- 22606456
TI  - Primary teratoma of the lesser sac: lesser sac teratoma.
AB  - Germ cell tumors predominantly involve the gonads but may rarely be found outside
      of the gonads, primarily in midline structures. We describe the case of a 27-year
      old male with an asymptomatic 8 cm teratoma located within the lesser sac of his
      omentum. This is the fourth case of a teratoma located within the lesser sac of
      the omentum, which provides the opportunity to make some comparisons. Finally, we
      discuss some of the etiologic theories behind extragonadal germ cell tumors and
      how they relate to teratomas in the lesser sac.

PMID- 22606457
TI  - Unusual presentation of rare case of papillary adenofibroma of cervix in a young
      woman.
AB  - Adenofibroma is an extremely rare benign biphasic neoplasm that is classified
      into the mixed epithelial and mesenchymal tumor group. These tumors tend to occur
      in postmenopausal and elderly women. We report the case of a large polypoidal
      mass per vagina occupying the whole pelvis in a young woman. Preoperative biopsy
      showed benign epithelial and mullerian mesenchymal components suggestive of
      mullerian adenofibroma. Total hysterectomy with bilateral salpingectomy was done.
      The diagnosis of papillary adenofibroma of cervix was made. The total surgery
      assured complete excision and permitted adequate sampling to exclude malignancy.

PMID- 22606458
TI  - A unique case of autoimmune retinopathy associated with anti-alpha-enolase
      antibodies.
AB  - Background. We report a case of autoimmune retinopathy associated with anti-alpha
      enolase antibodies with unique manifestations. Methods. A case report. Results. A
      30-year-old male experienced recurrent, primarily peripheral visual field
      disturbances and minimal photopsia, with interval symptom resolution. Fundus
      changes subsequently developed in areas corresponding to the previous visual
      field symptoms. Electroretinogram showed bilaterally symmetric abnormalities of
      light-adapted responses and suggested loss of photoreceptor function. Only anti
      alpha-enolase antibodies were detected on Western blot. Our patient noted
      cutaneous symptoms at the time of both episodes of visual symptoms, but not in
      the interim. Biomicroscopy revealed subtle small reddish spots in areas of the
      peripheral retina corresponding to the areas of the patient's visual field where
      he noted symptoms. To our knowledge these reddish spots have not been reported in
      autoimmune retinopathy and may clinically support in vitro and in vivo evidence
      that anti-alpha-enolase antibodies may target photoreceptors. Conclusions. Our
      patient demonstrates some unique features adding to the known characteristics of
      autoimmune retinopathy associated with anti-alpha-enolase antibodies. As more
      cases are reported, further understanding of the features and pathophysiology of
      this rare condition will hopefully be elucidated.

PMID- 22606459
TI  - Rapid recovery of visual acuity after lumboperitoneal shunt operation in
      malignant idiopathic intracranial hypertension.
AB  - Background. Idiopathic intracranial hypertension can cause rapid deterioration of
      visual acuity in some severe cases, and these cases are usually thought to have
      "malignant" form of this disease. Case. In this paper, we report on a 16-year-old
      girl who is a typical example for malignant idiopathic intracranial hypertension
      with a rapid recovery of visual acuity after lumboperitoneal shunt operation.
      Observations and Conclusions. Malignant form of idiopathic intracranial
      hypertension must be kept in mind in selected patients to avoid irreversible
      visual loss.

PMID- 22606460
TI  - Histopathological features in a case of peters' anomaly with acquired corneal
      staphyloma.
AB  - We report a case of corneal staphyloma histologically diagnosed as caused by
      Peters' anomaly. A 62-year-old male had a protruding opaque vascularized cornea
      that began to bulge from six months ago in the right eye. Since his right eye was
      blind and he wanted us to remove the eyeball for cosmetic improvement, we
      enucleated the affected eye. The enucleated tissue was fixed in formalin and
      embedded in paraffin for histological examination. Hematoxylin and eosin staining
      showed that the cornea lacked the posterior part of the corneal stroma and
      Descemet's membrane in the central region and the entire corneal endothelium. The
      corneal epithelium was keratinized. Collagen type I was strongly positive in
      peripheral cornea and weakly in protruding stroma. The cells labeled by
      antibodies against alphaSMA were scattered in the entire corneal stroma. As
      judged by the histological findings, the eye with the central corneal staphyloma
      was diagnosed as Peters' anomaly.

PMID- 22606461
TI  - Traumatic Endophthalmitis due to Cellulosimicrobium cellulans.
AB  - Purpose. To report a case of traumatic endophthalmitis due to Cellulosimicrobium
      cellulans. Design. Case report. Methods. Retrospective chart review. Results. To
      our knowledge, this is the first report of traumatic endophthalmitis due to C.
      cellulans, which did not respond to intravitreal antibiotics or repeat vitrectomy
      and ultimately led to the discovery of an occult intraocular foreign body.
      Conclusions. C. cellulans is a rare cause of endophthalmitis. Greater awareness
      of this bacterium in the ophthalmic literature as a cause of endophthalmitis and
      its association with foreign bodies may allow earlier and more purposeful
      intervention in future cases.

PMID- 22606462
TI  - Isolated bilateral congenital iris sphincter agenesis.
AB  - Purpose. We herein report a patient with bilateral congenital total iris
      sphincter agenesis with no other abnormality detected on systemic examination.
      Methods. A 24-year-old laborer presented to us for a routine checkup with
      complaint of photophobia and inability to work under sunlight. Examination
      revealed bilateral absence of sphincter and 6.5 mm pupil in both eyes in the
      undilated state. Results. Accommodation was poor in both eyes. Systemic
      examination was within normal limits. He was prescribed bifocal photochromic
      glasses for constant wear. Conclusions. Congenital sphincter agenesis can occur
      in an isolated form without systemic abnormalities which can be managed
      conservatively.

PMID- 22606463
TI  - Optical coherence tomography findings of retinal folds in nanophthalmos.
AB  - Aim. To report the optical coherence tomography (OCT) findings in three members
      of the same family with nanophthalmos associated with elevated papillomacular
      retinal fold. Methods. Complete ophthalmic examination as well as ultrasonography
      and OCT was performed in all patients. Results. Axial lengths ranged from 16.75
      mm to 17.48 mm and refractive errors ranged from +17.50 D to +20.50 D. Main
      fundus findings were the hyperopic crowded, cupless optic disc, and retinal fold
      through papillomacular region. Macular OCT scans revealed retinal fold with
      normal retinal pigment epithelium and choriocapillaris. Interpretation. It is
      presumed that the retinal folds in nanophthalmos result from a redundancy of the
      retinal layer caused by retarded growth of the scleral, choroidal, and retinal
      pigment epithelial layers. The anatomic information provided by the current study
      is consistent with this thesis.

PMID- 22606464
TI  - Travoprost induced granulomatous anterior uveitis.
AB  - Purpose. To report a case of granulomatous anterior uveitis caused by travoprost.
      Methods. Single observational case report. Results. A 71-year-old who was fit and
      healthy presented with bilateral granulomatous anterior uveitis 2 months after he
      was started on travoprost in both eyes. There was no past history of uveitis.
      Blood test and radiological investigation were unremarkable. Travoprost was
      stopped. The uveitis resolved on topical steroid treatment. A rechallenge with
      travoprost was attempted in one eye. The inflammation recurred in this eye only.
      This subsided with the cessation of travoprost alone without topical steroid.
      Conclusion. This is the first case report of travoprost causing granulomatous
      anterior uveitis. The uveitis recurred with a rechallenge. Changing the
      prostaglandin analogue to another topical treatment may be adequate to cease the
      inflammation.

PMID- 22606465
TI  - Management of a traumatic flap dislocation seven years after LASIK.
AB  - Seven years after uneventful laser in situ keratomileusis (LASIK), a 48-year-old
      woman presented one week after being hit with an iron cord with blurry vision,
      pain, and irritation. The injury resulted in traumatic flap dislocation,
      epithelial ingrowth, and macrostriae. Following epithelial removal, the flap was
      refloated and repositioned. Nine interrupted sutures were used to secure the
      flap. Three-weeks after surgery with no sutures remaining, the epithelial
      ingrowth and macrostriae had resolved with a visual acuity of 20/20.

PMID- 22606467
TI  - Limbitis secondary to autologous serum eye drops in a patient with atopic
      keratoconjunctivitis.
AB  - Purpose. Report a case of limbitis secondary to autologous serum eye drops in a
      patient with atopic keratoconjunctivitis. Design. Interventional case report.
      Methods. A 32-year-old African American female with atopic keratoconjunctivitis
      (AKC) presented with chronic dry eye and diffuse punctate epithelial erosions
      refractory to conservative treatment. She was initially managed with cyclosporine
      ophthalmic 0.05% in addition to preservative-free artificial tears and
      olopatadine hydrochloride 0.2% for 6 months. She was later placed on autologous
      serum eye drops (ASEDs) and 4 weeks into treatment developed unilateral limbitis.
      The limbitis resolved shortly after stopping ASEDs in that eye; however, the
      drops were continued in the contralateral eye, which subsequently developed
      limbitis within 2 weeks. ASEDs were discontinued in both eyes, and the patient
      has remained quiet ever since. Results. Patient with a history of AKC and no
      prior history of limbitis developed limbitis shortly after starting ASEDs, which
      resolved promptly after discontinuation of therapy with no subsequent recurrence
      of inflammation. Conclusion. ASEDs are widely used in the treatment of
      complicated or treatment refractory dry eye. The potential side effects should be
      kept in mind when prescribing ASEDs for any patient, especially in those with
      underlying immunological diseases and circulating inflammatory factors.

PMID- 22606466
TI  - Hepatocellular Carcinoma Metastasis to the Orbit in a Coinfected HIV+ HBV+
      Patient Previously Treated with Orthotopic Liver Transplantation: A Case Report.
AB  - Hepatocellular carcinoma rarely metastasizes to the orbit. We report a 45-year
      old male, HBV+, HIV+, with a past history of a liver transplant for ELSD (end
      stage liver disease) with hepatocellular carcinoma and recurrent HCC, who
      presented with proptosis and diplopia of the left eye. CT scans of the head
      revealed a large, irregular mass in the left orbit causing superior and lateral
      destruction of the orbital bone. Biopsy specimens of the orbital tumor showed
      features of metastatic foci of hepatocellular carcinoma. Only 16 other cases of
      HCC metastasis to the orbit have been described in literature, and this is the
      first case in a previously transplanted HIV+, HBV+ patient.

PMID- 22606468
TI  - Secondary Bilateral Angle Closure Glaucoma due to Topiramate.
AB  - We examined a 39-year-old female with severe headache and blurred vision. She was
      on topiramate, 50 mg once a day for one week because of migraine. Periorbital
      edema, chemosis, myopia, high intraocular pressures, and shallow anterior
      chambers were present at the initial examination. Iridocorneal angles were
      closed, ultrasound showed choroidal effusions. We stopped topiramate and started
      antiglaucoma treatment. After one week the intraocular pressure was 10 mm Hg in
      both eyes without treatment. A new ultrasound showed no choroidal effusions.
      Topiramate has been associated with acute secondary angle closure glaucoma as an
      idiosyncratic reaction to the drug. Physicians prescribing topiramate need to
      alert patients of this potential sight-threatening idiosyncratic reaction.

PMID- 22606469
TI  - A case of recurrent transient monocular visual loss after receiving sildenafil.
AB  - A 53-year-old man was attended to the Clinic Ophthalmic Center, Mansoura
      University, Egypt, with recurrent transient monocular visual loss after receiving
      sildenafil citrate (Viagra) for erectile dysfunction. Examination for possible
      risk factors revealed mild hypercholesterolemia. Family history showed that his
      father had suffered from bilateral nonarteritic anterior ischemic optic
      neuropathy (NAION). Physicians might look for arteriosclerotic risk factors and
      family history of NAION among predisposing risk factors before prescribing
      sildenafil erectile dysfunction drugs.

PMID- 22606470
TI  - Macular hole progression after intravitreal bevacizumab for hemicentral retinal
      vein occlusion.
AB  - Macular edema secondary to retinal vein occlusion is commonly being treated with
      off-label intravitreal bevacizumab with good outcomes. A significant reduction in
      macular edema and improvement in visual acuity is seen following such a treatment
      with no serious adverse effects. In the reported case, a full-thickness macular
      hole was noticed one month after intravitreal bevacizumab for macular edema
      secondary to hemicentral retinal vein occlusion. On a detailed review of the pre-
      and postoptical coherence tomography scans, it was realized that there was a
      preexisting stage 2-3 macular hole which was masked by the hemorrhages and edema
      at the fovea and the macular hole had progressed following the injection.

PMID- 22606471
TI  - Keratitis due to Chaetomium sp.
AB  - Aim. To describe keratitis due to Chaetomium sp. occurring in a 65-year-old woman
      who presented with a corneal ulcer with hypopyon of the right eye with a history
      of trauma by vegetable matter. Method. Multiple scrapings were obtained from the
      ulcer. A lactophenol cotton blue wet mount and a Gram-stained smear of the
      scrapings were made. Scrapings were also inoculated onto various culture media.
      Results. Direct microscopy of corneal scrapings revealed moderate numbers of
      septate fungal hyphae. Greenish-yellow-coloured fungal colonies with aerial
      mycelium were observed in culture of the corneal scrapes. On the basis of colony
      characteristics and conidial structure, the fungal isolate was identified as
      Chaetomium sp. The patient was treated with topical natamycin (5%) hourly and
      cyclopentolate 1% drops 3 times a day. After 4 weeks of therapy, the hypopyon had
      disappeared, the epithelial defect had healed, and the stromal infiltration had
      almost completely resolved; the visual acuity of the eye improved from hand
      movements to (1/2)/60. Conclusion. Fungi of the genus Chaetomium, which are rare
      causes of human disease (systemic mycosis, endocarditis, subcutaneous lesions),
      may also cause ocular lesions.

PMID- 22606472
TI  - Unilateral, isolated, paediatric lightning-induced cataract: a case report.
AB  - A six-year-old girl presented with gradual loss of vision in the left eye a year
      after sustaining a lightning strike while in her home. Examination revealed
      healed burns to her cheek, left arm, and right leg and a dense left cataract.
      There was no evidence of other ocular sequelae, and her right eye was normal.
      Cataract surgery and lens implantation were performed on the left eye with good
      results. Isolated, unilateral, paediatric cataract due to lightning is discussed.

PMID- 22606473
TI  - Bilateral diffuse uveal melanocytic proliferation presenting as small choroidal
      melanoma.
AB  - Purpose. To describe a patient with Bilateral Diffuse Uveal Proliferation who
      presented initially with a clinical picture consistent with choroidal melanoma.
      Methods. Presentation of a clinical case with fundus photos, fluorescein
      angiography, and optical coherence tomography. Results. A 70-year-old Caucasian
      male with history of esophageal cancer presented with an asymptomatic pigmented
      choroidal lesion in his left eye initially diagnosed as choroidal nevus. This
      lesion enlarged over the course of a year and developed orange pigment and
      increased thickness. A metastatic workup was negative, and a radioactive iodine
      plaque was placed on the left eye. Over the next six months, the visual acuity in
      his left eye decreased. His clinical picture was consistent with unilateral
      Diffuse Uveal Proliferation. A recurrence of his esophageal carcinoma with
      metastasis was discovered and palliative chemotherapy was initiated. Although his
      visual acuity improved in the left eye, similar pigmentary changes developed in
      the right fundus. His visual acuity in both eyes gradually decreased to 20/200
      until his death a year later. Conclusion. BDUMP should always be considered in
      the differential diagnosis of patients with pigmented fundus lesions and a
      history of nonocular tumors.

PMID- 22606474
TI  - Simultaneous occurrence of duane retraction syndrome with marfan syndrome.
AB  - Marfan syndrome (MFS) is an autosomal dominant disorder of connective tissue,
      while Duane retraction syndrome (DRS) is a congenital cranial dysinnervation
      disorder (CCDD) which can be transmitted as autosomal dominant disorder in 5-10%
      of patients. In this paper, we present an 8-year-old girl who presented with left
      eye DRS and bilateral subluxation of the lens associated with MFS in absence of
      familial involvement. To our knowledge this is the first case report of DRS with
      MFS. The occurrence of these syndromes together is very rare and appears to be
      coincidental.

PMID- 22606475
TI  - Ruthenium-106 plaque therapy for diffuse choroidal hemangioma in sturge-weber
      syndrome.
AB  - Diffuse choroidal hemangiomas associated with Sturge-Weber syndrome (SWS) are
      classically treated with external beam radiotherapy (EBR), but there are a few
      reports usually of single cases indicating the usefulness of plaque therapy. We
      present our observations on two cases of diffuse choroidal hemangiomas with
      exudative retinal detachment associated with SWS treated with Ruthenium-106
      plaque therapy. Outcomes included best-corrected visual acuity (BCVA) and
      regression in tumor thickness measured by ultrasonography. The initial BCVA of
      the affected eyes was counting fingers at 1 meter and light projection.
      Pretreatment tumors thickness was 3.5 mm and 4.7 mm. In a follow-up period of 18
      24 months, significant reduction in thickness of choroidal hemangiomas up to 1.2
      mm and 1.4 mm with prompt resolution of exudative retinal detachment was
      observed. BCVA achieved 20/200 and 20/400, respectively. The findings in this
      paper indicate that Ruthenium-106 plaque therapy is effective in treatment of
      diffuse choroidal hemangiomas associated with SWS.

PMID- 22606476
TI  - Laser vision correction on patients with sick optic nerve: a case report.
AB  - This 48-year-old white female with chronic optic disc edema is reported for the
      discussion of the management for the laser vision correction. Two procedures were
      considered, one was PRK (photorefractive keratectomy) and the other was LASIK
      (laser-assisted in-situ keratomileusis). A search strategy was developed to
      search evidence in the literature to support the decision in the selection of the
      better procedure for this patient. The evidences also were rigorously appraised
      for the validity. PRK was selected and performed on the patient with good
      outcome.

PMID- 22606477
TI  - Fundus autofluorescence in multiple evanescent white dot syndrome.
AB  - A patient complained of photopsia and vision loss in the left eye for two days,
      with visual acuity of 20/32. Right eye was normal. Funduscopy revealed foveal
      granularity and gray-white lesions in the posterior pole, mainly temporal to the
      fovea. The lesions (dots and spots), along with a few other areas surrounding
      them, showed hyperautofluorescence on autofluorescence imaging. Fluorescein
      angiogram (FA) depicted some early hyperfluorescent dots with late staining.
      Indocyanine green angiogram (ICGA) showed hypofluorescent lesions in a greater
      number compared with funduscopy, autofluorescence, and FA. Thirty days later,
      BCVA was 20/20 in both eyes and the complimentary exams were almost normal,
      despite an ICGA that showed few small hypofluorescent lesions. This case supports
      the hypothesis that the choroidal involvement occurs primarily in MEWDS, with
      secondary involvement of the RPE and the neurosensory retina.

PMID- 22606478
TI  - Unusual presentation of phacolytic glaucoma: simulating microbial keratitis.
AB  - The differential diagnoses for phacolytic glaucoma are acute angle closure
      glaucoma, open angle glaucoma with uveitis, neovascular glaucoma, and glaucoma
      secondary to trauma. We report an unusual case where the dislocated cataractous
      lens firmly adherent to the corneal endothelium evoked a cellular reaction
      similar to phacolytic glaucoma but clinically appeared like a deep corneal
      abscess. The 73-year-old lady presented with severe photophobia, pain, and
      redness in the left eye for two months despite being on antibiotics and
      antifungals. Anterior chamber wash revealed a cataractous lens buried within the
      infiltrate, which was removed and sent for histopathological examination.
      Postoperatively she was treated with topical ofloxacin, homatropine, dorzolamide,
      timolol, and tapering dose of steroids. Histological confirmation of
      inflammation, histiocytic response, and giant cells around the lens material
      confirmed the ongoing phacolytic process. Photophobia, pain, and redness subsided
      following removal of the lens and surrounding cellular reaction. At her last
      visit, four months after surgery, she was comfortable.

PMID- 22606479
TI  - Multiple, unilateral lisch nodules in the absence of other manifestations of
      neurofibromatosis type 1.
AB  - Lisch nodules associated with Neurofibromatosis Type 1 (NF1) are usually multiple
      and bilateral in nature. Here, we report a 21-year-old healthy, Caucasian female
      who was diagnosed with multiple, unilateral Lisch nodules during routine eye
      examination. A thorough history and physical examination revealed no other signs
      of NF1. We diagnosed the rare occurrence of numerous, unilateral Lisch nodules in
      the absence of additional features of NF1 in our patient and provide a discussion
      concerning the differential diagnosis of Lisch nodules as well as the potential
      genetic explanation of this finding.

PMID- 22606480
TI  - Ten Years of Severe Vitreomacular Traction Syndrome without Functional Damage
      Demonstrated by Optical Coherence Tomography.
AB  - Introduction. To describe anatomical and functional features in one patient with
      10 years of severe vitreomacular traction syndrome (VTS) without functional
      damage demonstrated by optical coherence tomography (OCT). Patient and Methods.
      One patient with a history of 10 years VTS, with best-corrected visual acuity of
      20/32, was followed up with OCT. Follow-up examinations, 3 months for the first
      year after diagnosis and every 6 months for the subsequent years, were performed.
      Results. Follow-up examinations showed no change anatomically and functionally.
      Far and near visual acuity was unchanged. OCT by Heidelberg Spectralis did not
      evidence differences from Stratus OCT images. Conclusion. VTS can be stable
      anatomically and functionally for 10 years. OCT is a valuable diagnostic tool in
      understanding the configuration of vitreomacular adhesion, followup, and
      eventually planning the surgical approach for operating on VTS.

PMID- 22606481
TI  - Scleral buckle extrusion associated with phthisis.
AB  - Exposure of implanted episcleral element is a rare complication of buckling
      procedures. We describe a 40-year-old man who presented to our clinic complaining
      of foreign body sensation and irritation in his left eye which lasted several
      months. The patient history was positive for bilateral rhegmatogenous retinal
      detachment which was treated with sclera buckling. Upon presentation the left eye
      demonstrated phthisis and an exposed and infected sclera buckle and explant in
      the lower quadrants. The explant was removed, and the patient was treated with
      antibiotics. This case suggests that wide encircling sclera element might erode
      through the conjunctiva of eyes undergoing phthisis. Integrity of the conjunctiva
      overlying episcleral implant should be evaluated during routine follow-up exams
      to exclude exposure of the implant particularly in eyes undergoing phthisis.

PMID- 22606482
TI  - Retinal vascular tortuosity in a patient with weill-marchesani syndrome.
AB  - Weill-Marchesani syndrome (WMS) is a rare connective tissue disorder with
      characteristic phenotypic skeletal and ocular manifestations. A 28-year-old
      myopic female presented with an 8-month history of bilateral blurred vision. On
      examination, she was noted to be of short stature with brachydactyly. On ocular
      examination, she was found to be spherophakic with bilateral inferiorly
      subluxated lenses. Serum and urine homocysteine were normal and a syphilis screen
      was negative. A diagnosis of Weill-Marchesani syndrome was made. Fundoscopy
      revealed bilateral tortuous retinal vessels. We report the first illustrated case
      of retinal vascular tortuosity as an ocular manifestation of Weill-Marchesani
      syndrome.

PMID- 22606483
TI  - Nonischemic central retinal vein occlusion in an adolescent patient with
      ulcerative colitis.
AB  - Inflammatory bowel disease (IBD) can present with extraintestinal manifestations
      occasionally involving the eye. Retinal vein occlusions are rarely seen and have
      never been reported in the pediatric population though vascular thrombosis can be
      associated with IBD. Here, we present a case of what we believe is the youngest
      reported patient with nonischemic central retinal vein occlusion (CRVO).

PMID- 22606484
TI  - A case of squamous cell carcinoma of conjunctiva as initial sign of systemic
      cancers.
AB  - The purpose of this report is to present the findings in a case of squamous cell
      carcinoma (SCC) of the conjunctiva which was the initial sign of systemic
      cancers. A 94-year-old woman without known systemic diseases developed a mass in
      her right conjunctiva. She was referred to our hospital 5 months after the onset.
      She was diagnosed with conjunctival SCC by biopsy. Systemic CT before the surgery
      revealed multiple liver lesions, lung legions, and a large mass surrounding the
      appendix. The patient requested the surgery, and the main aim of the surgery was
      cosmesis. Histopathological examinations of the specimen led us to the final
      diagnosis as SCC. She did not receive any other therapy because of her age. As no
      other surgical procedures were undertaken, it is uncertain as to whether the
      conjunctival lesion was primary or secondary. Although, it is extremely rare that
      SCC of the conjunctiva is the initial sign of systemic cancers, careful systemic
      examinations to find other cancers should be made.

PMID- 22606485
TI  - A bilobed schwannoma in roof of orbit: a rare case report.
AB  - In this paper, we report a case of bilobed schwannoma, presented in the roof of
      orbit arising from supraorbital nerve. A 62-year male presented with a nontender
      mass in superior part of orbit and eccentric proptosis. Visual acuity and rest of
      ocular examination were normal. CT scan and MRI orbit revealed an extraconal
      homogenous bilobed mass, of size 3.5 to 2.5 cms in roof of orbit. Fine needle
      aspiration cytology was done, which was suggestive of schwannoma a peripheral
      nerve tumor. Successful surgical excision of intact bilobed schwannoma was done
      with careful separation and preservation of supraorbital nerve from which it was
      originated. Postoperative period was uneventful though rare, less than 1%,
      schwannoma can present as painless mass in the orbit and proptosis. Treatment of
      choice is surgical excision of intact tumor to prevent recurrence and
      preservation of peripheral nerve from which it arises.

PMID- 22606486
TI  - Downbeat nystagmus induced by sedation in LASIK.
AB  - Nystagmus was elicited during lasik under sedation in two patients that were
      treated for depression. Nystagmus was not present before or after surgery.
      Nystagmus can be pharmacologically induced and can be a hazard to refractive
      surgery.

PMID- 22606487
TI  - Femtosecond laser refractive surgery after descemet stripping-automated
      endothelial keratoplasty.
AB  - Purpose. To report the use of femtosecond laser-assisted in situ keratomileusis
      (LASIK) in the treatment of hyperopia subsequent to Descemet stripping-automated
      endothelial keratoplasty (DSAEK). Methods. Interventional case report. Results. A
      66-year-old woman with Fuchs endothelial dystrophy developed bullous keratopathy
      after cataract surgery in her right eye. She underwent DSAEK with a significant
      postoperative hyperopic shift in her refraction. Thirteen months after DSAEK, she
      underwent wavefront-guided, femtosecond laser-assisted LASIK (IntraLase, Inc.,
      Irvine, CA/AMO, Inc., IL, USA). Pretreatment unaided visual acuity was 20/120,
      and best-corrected visual acuity was 20/20 with a refraction of +3.25/-0.50 *
      170. One year after laser refractive correction, unaided visual acuity was 20/20
      with a refraction of +0.25/-0.75 * 160. Conclusion. To our knowledge, this is the
      first paper on the successful treatment of hyperopic shift related to DSAEK with
      wavefront-guided, femtosecond laser-assisted LASIK.

PMID- 22606488
TI  - Complication of salmonella bacteremia in a case of treated fungal
      endophthalmitis.
AB  - This is to report a case of bacteremia caused by Salmonella typhi in a treated
      unilateral fungal endogenous endophthalmitis in an 18-year-old male from one of
      the South Asian countries. Microbiological and molecular investigations were
      carried out on the eviscerated material and routine blood culture was carried
      out. Direct examination of eviscerated material revealed the presence of fungal
      filaments. However, Salmonella typhi was isolated from both specimens, which was
      confirmed by Polymerase chain reaction targeting the 16SrRNA gene, sequencing,
      and random amplification of polymorphic DNA showed that they belonged to the same
      clone. The presence of Salmonella bacteremia in a treated unilateral fungal
      endophthalmitis, among young adult patients is rare and systemic symptoms should
      be investigated.

PMID- 22606489
TI  - Trichilemmal cyst of the eyelid: masquerading as recurrent chalazion.
AB  - A 52-years-old female presented with a history of a painless, progressive
      swelling in the left lower eyelid of one-year duration. The lesion was excised
      twice as a chalazion and recurred. Excisional biopsy of the mass was performed
      and histopathological findings were consistent with those of trichilemmal cyst.
      We report a rare case of trichilemmal cyst of the eyelid which was masquerading
      as chalazion for which the patient had undergone multiple surgeries. Wide
      excision was done and diagnosis was confirmed on histopathology. There was no
      recurrence seen till 2 months of postoperative period. Trichilemmal cyst,
      although rare, should be considered as differential diagnosis of recurrent
      chalazion.

PMID- 22606490
TI  - Orbital Burkitt's Lymphoma: An Aggressive Presentation.
AB  - Objective. To present the case of an aggressive orbital Burkitt's lymphoma.
      Methods. Chart review. Case Presentation. A 24-year-old Haitian man came to our
      clinic complaining of rapidly progressive right eye proptosis. On examination, a
      large friable exophytic mass with necrotic areas and exudative/hemorrhagic
      secretions was noted protruding from his right orbit. A biopsy revealed the
      characteristic "starry-sky" appearance of a Burkitt lymphoma. The patient died
      shortly after due to complications from systemic involvement. Discussion. This
      case is meant to raise physicians' awareness on the healthcare situation in some
      underdeveloped countries, emphasizing the importance of education in preventive
      medicine.

PMID- 22606491
TI  - Pasteurella canis Isolation following Penetrating Eye Injury: A Case Report.
AB  - A 3-year-old boy presented with history of trauma to the left eye after he
      accidentally injured his eye with a broom stick made up from coconut skewers.
      There was history of cats as their pets but not dogs. Ocular examination revealed
      left superonasal conjunctival laceration and scleral perforation with prolapsed
      vitreous. Fundus examination showed minimal vitreous haemorrhage and flat retina.
      Conjunctiva swab at the wound site was sent for gram staining, culture, and
      sensitivity. He underwent scleral suturing, vitreous tap, and intravitreal
      injection of Ceftazidime and Amikacin. Vitreous tap was sent for gram stained,
      culture and sensitivity. Postoperatively, he was started empirically on IV
      Ciprofloxacin 160 mg BD, Guttae Ciprofloxacin, and Guttae Ceftazidime.
      Conjunctiva swab grew Pasteurella canis which was sensitive to all Beta lactams,
      Ciprofloxacin, Chloramphenicol, and Aminoglycoside. Post-operative was
      uneventful, absent signs of endophthalmitis or orbital cellulitis.

PMID- 22606492
TI  - Orbital Myiasis: Due to Invasion of Larvae of Flesh Fly (Wohlfahrtia magnifica)
      in a Child; Rare Presentation.
AB  - Wohlfahrtia magnifica larvae cause myiasis in mammals, mainly in sheep and rarely
      in human. In human it may infest the ear, eye, mouth or nose, damaging living
      tissues. We report a case of ocular myiasis in 1.5 years old child belonging to
      urban slum after history of minor injury on left upper lid due to fall from bed.
      The purpose of reporting this case is to highlight the ocular association of W.
      magnifica.

PMID- 22606493
TI  - Sands of sahara after LASIK in avellino corneal dystrophy.
AB  - We report the case of a patient diagnosed with Avellino corneal dystrophy (ACD)
      who developed diffuse interstitial keratitis following excimer laser insitu
      keratomileusis (LASIK). ACD is an autosomal dominant corneal dystrophy
      characterized by multiple asymmetric stromal opacities that impair vision.
      Accepted treatments for this condition include corneal transplantation and
      phototherapeutic keratectomy (PTK). Our patient underwent LASIK at another
      institution to correct myopia. LASIK and photorefractive keratectomy (PRK) are
      usually contraindicated in ACD for the high risk of disease recurrence and
      postoperative complications. The patient came to our attention lamenting blurry
      vision, decreased visual acuity, and photophobia. Ophthalmologic examination
      revealed bilateral interstitial keratitis, also known as "sands of Sahara", a
      seldom-seen complication of LASIK characterized by fine and diffuse granular
      infiltrates at the surgical flap interface.The risk of developing interstitial
      keratitis, as in the case presented here, represents another valid reason for
      avoiding LASIK in patients with ACD.

PMID- 22606494
TI  - The masquerades of a childhood ciliary body medulloepithelioma: a case of chronic
      uveitis, cataract, and secondary glaucoma.
AB  - Ciliary body medulloepitheliomas in childhood often masquerade other intraocular
      conditions due to its insidious nature as well as its secondary effects on
      proximal intraocular tissues in the anterior chamber. We report a case where a
      ciliary body medulloepithelioma in a two-year-old boy presents with chronic
      uveitis, cataract, and an uncontrolled secondary glaucoma after an innocuous
      blunt ocular trauma. The diagnosis was only made after the occurrence of a
      ciliary body mass. We discuss the clinical features of ciliary body
      medulloepitheliomas, the implications of a delayed diagnosis and treatment as
      well as the concern of periorbital tumor seeding with the use of an aqueous shunt
      implant in this case.

PMID- 22606495
TI  - Orbitotemporal neurofibromatosis: case report.
AB  - Plexiform neurofibromas occur in about 60% of neurofibromatosis type 1(NF-1)
      patients and can lead to severe morbidity by disfigurement or compression of
      vital structures. Moreover, these tumors can undergo malignant transformation.
      Both focal and localized bone abnormalities are part of the phenotypic expression
      of NF-1. We report a rare case of severe cranioorbital plexiform
      neurofibromatosis in a young male and discuss the classification, clinical
      features, and various treatment options of orbit-temporal neurofibromatosis type
      1.

PMID- 22606496
TI  - Presumed sturge weber syndrome in a haitian boy: a case of delayed diagnosis.
AB  - Purpose. To report an untypical presentation of a presumed Sturge-Weber Syndrome
      (SWS), and to highlight the indispensable value of thorough clinical examination
      as primary means for proper diagnosis and management. Methods. Chart review.
      Results. A 7 year-old boy, with a long history of ocular symptoms and an
      unspecified ocular surgery, presents with a painful blind left eye. Based on
      clinical examination, the suspicion of SWS was raised. The presentation was not
      typical in the sense that no evident port-wine stain was observed on the face.
      However, facial asymmetry and gum discoloration were guiding clinical clues to
      pursue further investigations. Unfortunately, due to poor treatment response, the
      patient underwent enucleation. Tissue pathology revealed diffuse choroidal
      hemangiomas, consistent with the diagnosis of SWS. Conclusion. SWS presents with
      hamartomatous malformations and venous dilation affecting the skin, central
      nervous system and eye. The ocular involvement may vary, with the most common
      complications being glaucoma, buphthalmos and diffuse choroidal hemangiomas. This
      case report helps remind physicians of the importance of a thorough clinical
      examination, and highlights the ophthalmologists' responsibility of examining
      beyond the eye.

PMID- 22606497
TI  - Cystoid macular edema in acute presentation of central retinal artery occlusion.
AB  - A seventy-six-year-old lady with poor vision of the left eye due to previous
      retinal detachment presented with acute visual loss of her right eye secondary to
      central retinal artery occlusion. Clinical examination showed a pale right optic
      disc, macular edema, and a cherry red spot. Optical coherence tomography done
      four hours after onset showed right acute cystoid macular edema and diffuse inner
      retinal thickening. Subsequent treatment with intravenous carbonic anhydrase
      inhibitor resulted in some visual improvement. Central retinal artery occlusion
      has been known to produce diffuse intraretinal edema instead of cystoids changes.
      We would like to discuss a case of acute cystoid macular edema in acute central
      retinal artery occlusion.

PMID- 22606498
TI  - Neurosyphilis presenting as asymptomatic optic perineuritis.
AB  - Introduction. Syphilis is a sexually transmitted disease that is known as "the
      great imitator" due to its wide variety of clinical presentations, including
      ocular disorders. There has been an increase in the rate of syphilis in the
      United States, especially in persons with HIV. We report a case of optic
      perineuritis in an asymptomatic male secondary to central nervous system (CNS)
      syphilis. Case Report. A 41-year-old man was found to have bilateral disc edema
      on a routine exam. Brain MRI was unremarkable, and lumbar puncture revealed a
      normal opening pressure, with an elevated cerebrospinal fluid white cell count.
      Orbit MRI showed optic nerve sheath expansion and enhancement, consistent with
      optic perineuritis. He tested positive for syphilis based on serum RPR and FTA
      ABS. Conclusion. Ophthalmologic findings, including disc edema, may be the
      presenting features of CNS syphilis. Even in asymptomatic persons, perineuritis
      should be considered early, as diagnosis and treatment are imperative given the
      progressive nature of the disease.

PMID- 22606499
TI  - Congenital simple hamartoma of retinal pigment epithelium: clinical and imaging
      findings.
AB  - Congenital simple hamartoma of retinal pigment epithelium (CSHRPE) is a rare,
      asymptomatic, and incidentally detected benign lesion. However, it is very
      important to do the differential diagnosis from other pigmented retinal lesions.
      Its clinical presentation and imaging findings are very helpful in doing this
      differentiation. This paper presents clinical and imaging findings of a 56-year
      old woman with incidentally detected CSHRPE. The lesion was small, heavily
      pigmented, well circumscribed, and slightly elevated. Optical coherence
      tomography (OCT) scanning was diagnostic and showed an elevated retina at the
      site of the lesion, increased optical reflectivity on its inner surface, optical
      shadowing of deeper structures, and clearly cut tumor margins. Ocular
      ultrasonography, fluorescein angiography, and fundus autofluorescence imaging
      which is firstly described in this report did not show any characteristic
      finding.

PMID- 22606500
TI  - Congenital unilateral corneal anaesthesia with microphthalmos: a case report.
AB  - Congenital corneal anaesthesia (CCA) is an uncommon condition difficult to
      diagnose. We report the case of a 20-month-old boy who presented with unilateral
      congenital corneal anaesthesia. The child was referred with a persistent corneal
      epithelial defect, unresponsive to symptomatic local treatment for over 10
      months. Intensive topical treatment and strict corneal protection led to quick
      corneal healing. Congenital corneal anaesthesia occurs either alone or in
      association with neurological diseases or systemic congenital abnormalities. It
      is important to search for corneal anaesthesia in children with chronic
      ulcerations of the cornea and self-inflicted injuries. Early diagnosis and
      treatment are important due to the risk of poor visual prognosis. Management of
      CCA should aim for the prevention of epithelial defects and is a life-long
      process.

PMID- 22606501
TI  - Asymptomatic Intracorneal Graphite Deposits following Graphite Pencil Injury.
AB  - Reports of graphite pencil lead injuries to the eye are rare. Although graphite
      is considered to remain inert in the eye, it has been known to cause severe
      inflammation and damage to ocular structures. We report a case of a 12-year-old
      girl with intracorneal graphite foreign bodies following a graphite pencil
      injury.

PMID- 22606502
TI  - Periocular myxoma in a child.
AB  - Myxomas are locally invasive, benign mesenchymal neoplasms with odontogenic,
      osteogenic, or soft tissue origin. Facial myxomas probably account for less than
      0.5% of all paranasal sinus and nasal tumors. We report a case of a left painless
      periocular mass in a 11-month-old girl. The lesion was resected with a clinical
      diagnosis of lacrimal sac tumor. Histopathology and immunohistochemistry proved
      the tumor to be a myxoma. There has been no recurrence after 4 years of followup.
      Midfacial myxomas should be differentiated from other benign and malignant tumors
      such as dermoid, hamartoma, neurofibroma, nasolacrimal duct cyst, and sarcomas in
      particular embryonal rhabdomyosarcoma. Because of the infiltrative nature of
      these tumors, a wide surgery is required to achieve clear resection margins and
      avoid recurrence.

PMID- 22606503
TI  - Late-onset glaucoma-filtrating bleb leak in a penetrating keratoplasty patient: a
      case report.
AB  - Introduction. Late-onset bleb leaks occur more frequently after the use of
      adjunctive antimetabolites and require surgical management to seal and preserve
      filtrating bleb. Case Presentation. A 48-year-old female presented with decreased
      visual acuity for five days in her left eye. She had a left penetrating
      keratoplasty one year earlier and two trabeculectomies 7 years earlier. Visual
      acuity was hand motions, intraocular pressure was 3 mmHg, corneal graft was
      clear, mature cataract was present, and axial length was 30.48 mm. The
      conjunctiva covering the superotemporal sclerotomy was avascular, flat, and
      partially lost. After heavily painting the bleb with a fluorescein, late-onset
      point leak was revealed. Overlying conjunctiva was excised. The atrophic,
      irregular, and partially absent scleral flap was covered by a processed human
      pericardium graft and conjunctival advancement. Postoperatively, intraocular
      pressure stabilized around 16 mmHg. After four months, phacoemulsification and
      intraocular lens implantation were performed. Visual acuity did not exceed 0.1
      (in decimal notation) due to degenerative myopia-related macular atrophy. Corneal
      graft remained clear at her 6-month followup period. Conclusion. Surgical bleb
      revision using a pericardium graft and conjunctival advancement seems to be an
      effective method for treating late bleb leaks. However, careful follow-up is
      required for detecting recurrent leaks and elevated intraocular pressure.

PMID- 22606504
TI  - Pigmentation of the cornea secondary to tinted soft contact lens wear.
AB  - Purpose. To report a case of pigmented corneal iron lines following use of tinted
      soft contact lenses (CL). Methods. A retrospective case report. Results. A 16
      year-old girl was referred with suspected CL-related keratopathy OU, having
      recently switched to tinted soft monthly disposable CLs (8.4/14.0 -3.00 OD, -3.25
      OS Aquamarine SofLens Natural Colours, Bausch and Lomb, New York, USA). Both
      corneas exhibited symmetric superficial corneal pigmented iron lines, which
      gradually disappeared following discontinuation of CL wear. Conclusions.
      Pigmented corneal rings have been reported in normal ageing corneas, in certain
      pathological conditions, and in association with altered corneal topography
      following LASIK and orthokeratology. We suspect a poorly fitting CL resulted in
      localised tear pooling between the CL and cornea, and subsequent iron pigment
      deposition, similar to that seen with orthokeratology. Cosmetic CLs bought via
      the Internet can be used in an unsupervised manner, with possible impacts on
      visual function and potential complications.

PMID- 22606505
TI  - Compressive Optic Neuropathy Caused by Orbital Non-Hodgkin's Lymphoma.
AB  - Purpose. To present a unique case of Non-Hodgkin's-Lymphoma- (NHL) associated
      compressive optic neuropathy. Method. An 89-year-old male presenting with acute
      unilateral visual loss and headache. Results. Patient was initially diagnosed
      with occult giant cell arteritis; however after visual acuity deteriorated
      despite normal inflammatory markers, an urgent MRI scan revealed an extensive
      paranasal sinus mass compressing the optic nerve. Conclusion. Paranasal sinus
      malignancies occasionally present to the ophthalmologist with signs of optic
      nerve compression and must be included in the differential diagnosis of acute
      visual loss.

PMID- 22606506
TI  - Descemet's Stripping-Automated Endothelial Keratoplasty for Traumatic Aniridia
      and Aphakia.
AB  - This Interventional case reports a challenging case of descemet's stripping
      automated endothelial keratoplasty (DSAEK) in a young male patient with traumatic
      aniridia, aphakia, and corneal edema. Surgery was planned in two stages; first
      was implantation of aniridia intraocular lens (AIOL), few months later, DSAEK
      procedure was performed. Successful outcome of both procedures was achieved as
      measured by the stability of the AIOL, clarity of the cornea, attachment of the
      lenticule, and improvement in vision. Aniridia implant supports a sufficient
      amount of air in the anterior chamber especially if the posterior segment is well
      formed, while providing the required lens power to improve vision. DSAEK
      procedure challenges that include iris defects and aphakia may be overcome by
      stepwise planning of the procedure.

PMID- 22606507
TI  - Growth Impairment and Nutritional Deficiencies in a Cow's Milk-Allergic Infant
      Fed by Unmodified Donkey's Milk.
AB  - We report a case of growth impairment and nutritional deficiencies in a five
      month infant fed by unmodified donkey's milk. We discuss the energy and
      macronutrient daily intake from donkey's milk and the nutritional consequences
      that can occur if this kind of milk is used unmodified in the first year of life.

PMID- 22606508
TI  - Prune belly syndrome.
AB  - Prune belly syndrome is a rare congenital disorder of the urinary system,
      characterized by a triad of abnormalities. The aetiology is not known. Many
      infants are either stillborn or die within the first few weeks of life from
      severe lung or kidney problems, or a combination of congenital anomalies.

PMID- 22606509
TI  - Joubert syndrome presenting with motor delay and oculomotor apraxia.
AB  - We describe two sisters who presented in early childhood with motor delay and
      unusual eye movements. Both demonstrated hypotonia and poor visual attention. The
      older girl at 14 weeks of age showed fine pendular horizontal nystagmus more
      pronounced on lateral gaze, but despite investigation with cranial MRI no
      diagnosis was reached. The birth of her younger sister four years later with a
      similar presentation triggered review of the sisters' visual behaviour. Each had
      developed an unusual but similar form of oculomotor apraxia (OMA) with head
      thrusts to maintain fixation rather than to change fixation. MRI of the older
      sibling demonstrated the characteristic "molar tooth sign" (MTS) of Joubert
      syndrome which was subsequently confirmed on MRI in the younger sibling. We
      discuss the genetically heterogeneous ciliopathies now grouped as Joubert
      syndrome and Related Disorders. Clinicians need to consider this group of
      disorders when faced with unusual eye movements in the developmentally delayed
      child.

PMID- 22606510
TI  - Familial recurrence of cerebral palsy with multiple risk factors.
AB  - The recurrence of cerebral palsy in the same family is uncommon. We, however,
      report on two families with two or more affected siblings. In both families,
      numerous potential risk factors were identified including environmental,
      obstetric, and possible maternal effects. We hypothesize that multiple risk
      factors may lead to the increased risk of recurrence of cerebral palsy in
      families. Intrinsic and maternal risk factors should be investigated in all cases
      of cerebral palsy to properly counsel families on the risk of recurrence. Recent
      studies of genetic polymorphisms associated with cerebral palsy are considered
      with reference to our observations in these two families.

PMID- 22606511
TI  - Intrauterine extremity gangrene and cerebral infarction at term: a case report.
AB  - Intrauterine extremity gangrene in combination with cerebral infarction is a
      serious and rare event. We present a case with a healthy mother who gave birth to
      a child with this condition. At term, the mother presented at the antenatal
      clinic with decreased fetal movements. Cardiotocography (CTG) showed signs of
      fetal distress and a caesarean section was performed. The left arm of the newborn
      was found gangrenous. Amputation of the arm was necessary and the child was
      subsequently treated with anticoagulant therapy due to thrombosis and cerebral
      infarction in the left hemisphere found by magnetic resonance imaging (MRI). At
      one year of age the boy was doing well and had prosthesis as a left arm. He had
      no signs of further complications. Despite thorough examination of the parents
      and the child, the reason for the thrombosis is still unknown.

PMID- 22606512
TI  - Congenital Central Hypothyroidism due to a Homozygous Mutation in the TSHbeta
      Subunit Gene.
AB  - Congenital central hypothyroidism (CCH) is a rare condition occurring in 1 :
      20000 to 1 : 50000 newborns. As TSH plasma levels are low, CCH is usually not
      detected by TSH-based neonatal screening for hypothyroidism, and, as a result,
      diagnosis is often delayed putting affected children at risk for developmental
      delay and growth failure. We report on a girl with isolated central
      hypothyroidism due to a homozygous one-base pair deletion (T313del) in exon 3 of
      the TSHbeta subunit gene. The molecular genetic and typical radiologic findings
      are discussed, and a systematic diagnostic workup for congenital central
      hypothyroidism is proposed. Physicians need to be aware of this rare condition to
      avoid diagnostic delay and to install prompt replacement therapy.

PMID- 22606513
TI  - A pain in the buttock.
AB  - Spondylolysis, a fracture of the pars interarticularis, is a common source back
      pain in children and adolescents. While the incidence is significantly higher in
      Asian and Inuit populations, it is never seen in nonambulatory children and is
      most commonly associated with athletic activities that involve extension or
      rotational deformity about the spine suggesting a functional component. Given
      that the associated pain is typically insidious in onset, lacks preceding trauma,
      and is accompanied by muscular spasm, prompt diagnosis requires a high index of
      suspicion, familiarity with provocative testing, and knowledge of the appropriate
      radiographic evaluation. Treatment requires cessation of athletic activity,
      bracing, and rest for a minimum of four to six weeks, or until symptomatic and
      radiographic resolution.

PMID- 22606514
TI  - Warkany syndrome: a rare case report.
AB  - Warkany syndrome 2 or Trisomy 8 mosaicism (T8M) is a well-described, but very
      rare, chromosomal abnormality. The phenotype is extremely variable ranging from
      normal individual to severe malformation syndrome and because of this
      variability, this condition often goes undiagnosed. We report trisomy 8 mosaicism
      (T8M) in a 3-year-old boy evaluated for facial dysmorphism and delayed
      development.

PMID- 22606515
TI  - Unilateral lymphangiomatous polyp of the palatine tonsil in a very young child: a
      clinicopathologic case report.
AB  - Childhood lymphangiomatous polyp of the palatine tonsil is a very unusual lesion
      found in the head and neck. Tonsillectomy has been reported to be the curative
      procedure of choice for this lesion. We report a case of a very young child with
      unilateral lymphangiomatous polyp of the palatine tonsil.

PMID- 22606516
TI  - Vancomycin hypersensitivity diagnosed by lymphocyte blast transformation.
AB  - A 15-year-old male admitted for Pott's puffy tumor developed recurrent episodes
      of fever, diffuse morbilliform rash, eosinophilia, and tubulointerstitial
      nephritis while on multiple antibiotics. Lymphocyte blast transformation (LBT), a
      method of detecting cellular immune response by measuring levels of interferon
      gamma (IFN-gamma), was used to diagnose vancomycin hypersensitivity and guide
      antibiotic selection.

PMID- 22606517
TI  - Abdominal compartment syndrome secondary to chronic constipation.
AB  - Abdominal compartment syndrome (ACS) is defined as an elevated intraabdominal
      pressure with evidence of organ dysfunction. The majority of published reports of
      ACS are in neonates with abdominal wall defects and in adults following trauma or
      burns, but it is poorly described in children. We describe the unusual
      presentation of an 11-year-old boy with a long history of chronic constipation
      who developed acute ACS requiring resuscitative measures and emergent
      disimpaction. He presented with a 2-week history of increasing abdominal pain,
      nausea, diminished appetite and longstanding encopresis. On exam, he was
      emaciated with a massively distended abdomen with a palpable fecaloma. Abdominal
      XR confirmed these findings. Within 24 hours of presentation, he became
      tachycardic and oliguric with orthostatic hypotension. Following two enemas, he
      acutely deteriorated with severe hypotension, marked tachycardia, acute
      respiratory distress, and a declining mental status. Endotracheal intubation,
      fluid boluses, and vasopressors were commenced, followed by emergent surgical
      fecal disimpaction. This resulted in rapid improvement in vital signs. He has
      been thoroughly investigated and no other condition apart from functional
      constipation has been identified. Although ACS secondary to constipation is
      extremely unusual, this case illustrates the need to actively treat constipation
      and what can happen if it is not.

PMID- 22606518
TI  - Splenomegaly, cardiomegaly, and osteoporosis in a child with Gaucher disease.
AB  - A 15-month-old girl, born to the consanguineous parents, was referred with the
      sign of massive splenomegaly associated with thrombocytopenia and anemia. Plasma
      Chitotriosidase estimation was carried out as a screening test and was found to
      be normal with reduced activity of beta-glucosidase in leucocytes suggestive of
      Gaucher disease. At the age of 4 years, severe osteoporosis and cardiomegaly with
      pulmonary congestion were observed in the child. Molecular analysis for GBA gene
      has revealed homozygous status for L444P (c.1448C) in the proband, whereas
      parents and two elder sisters were found to be heterozygote. Prenatal study
      during the fourth pregnancy was carried out from cultured chorionic villi for
      beta-glucosidase, which was in the carrier range. Further confirmation of the
      carrier status was carried out from amniotic fluid DNA and was found to be
      heterozygous for L444P (c.1448C) in the GBA gene. This case demonstrates that
      children with the sign of splenomegaly with anemia and thrombocytopenia need to
      be screened for Gaucher disease, and molecular study can further help to confirm
      the heterozygous status, where prenatal study by enzyme investigation demonstrate
      heterozygous condition.

PMID- 22606519
TI  - A Rare Case Report of Fatal Fulminant Hepatic Failure in a Child due to Mixed
      vivax and falciparum Infection.
AB  - Malaria remains an overwhelming problem in the tropical developing countries,
      with 300 to 500 million new cases and about a million deaths per year (Mishra et
      al., 2003). Malaria is a potentially life-threatening disease in the tropics.
      Jaundice is one of the severe manifestations of falciparum malaria. Its incidence
      (Mishra et al., 2003). varies between 10 and 45% in different reports and is seen
      more in adults than in children. Jaundice may vary from mild to very severe.
      However, clinical signs of hepatic encephalopathy (such as liver flaps) are never
      seen unless there is presence of concomitant viral hepatitis (WHO, 2000). Our
      case is a 6-year-old female child presented with fever, jaundice, and anasarca.
      Peripheral smear showed trophozoites and schizonts of Plasmodium (P.) vivax and
      trophozoites and gametocytes of P. falciparum. Viral markers for hepatitis were
      negative. She developed fulminant hepatic failure and expired after 26 hours of
      admission.

PMID- 22606520
TI  - Adolescent with Rhabdomyolysis due to Undiagnosed Hypothyroidism.
AB  - Exercise-induced rhabdomyolysis has been described in military recruits, trained
      athletes and daily runners. Statin use, quail ingestion, infection by Epstein
      Barr virus (EBV), and hypothyroidism, though rare, are risk factors for the
      development of rhabdomyolysis. We describe the case of a 15-year-old female who
      presented with myalgias, weakness, and pigmenturia following marching band
      practice. Laboratory tests confirmed an elevated creatine kinase (CK) level as
      well as a profound hypothyroid state. Muscle biopsy revealed severe muscle
      necrosis and myositis. Treatment with levothyroxine resulted in obtaining an
      euthyroid state and regain of muscle strength as well as decrease in CK levels.
      Although rare, hypothyroidism should be considered as a potential cause of
      rhabdomyolysis in pediatric patients undergoing a myopathy workup.

PMID- 22606521
TI  - Successful utilization of high-flux hemodialysis for treatment of vancomycin
      toxicity in a child.
AB  - Vancomycin is routinely used for empiric antibiotic therapy in children. Higher
      serum-concentration targets for serious infections are now being recommended.
      This recommendation may result in aggressive dosing with increased potential for
      toxicity. We report a case of a pediatric patient who developed vancomycin
      toxicity and associated oliguric renal failure who was treated effectively with
      high-flux hemodialysis for vancomycin toxicity, clearing serum concentrations of
      vancomycin by over 75% in only 6 hours (213.2 mcg/mL to 51.8 mcg/mL) with
      subsequent return to baseline renal function and without adverse sequelae. While
      not historically considered a viable option for drug removal in cases of
      toxicity, new high-flux hemodialysis techniques can remove significant
      percentages of vancomycin in short periods of time.

PMID- 22606522
TI  - An unusual case of gastrointestinal bleeding.
AB  - A 10-year-old boy presented with a 3-day history of worsening abdominal pain,
      fever, emesis and melena. Abdominal ultrasound revealed a right upper quadrant
      mass that was confirmed by computed tomography angiogram (CTA), which showed an 8
      cm well-defined retroperitoneal vascular mass. (123)Iodine
      metaiodobenzylguanidine ((123)MIBG) scan indicated uptake only in the abdominal
      mass. Subsequent biopsy revealed a paraganglioma that was treated with
      chemotherapy. This case represents an unusual presentation of a paraganglioma
      associated with gastrointestinal (GI) bleeding and highlights the utility of CTA
      and (123)MIBG in evaluation and treatment.

PMID- 22606523
TI  - Erythema nodosum in a child with celiac disease.
AB  - Erythema nodosum is an acute, nodular, erythematous eruption usually limited to
      the extensor aspects of the lower legs. It could be idiopathic or associated with
      other systemic diseases. We, herein, report a phenotypically healthy, ten-year
      old boy who presented with erythema nodosum in whom serological tests of
      autoimmunity and intestinal histological examination were compatible with celiac
      disease. The eruption resolved within 2 months following a gluten-free diet.
      Therefore, the possibility that erythema nodosum represents an extraintestinal
      manifestation of celiac disease should be kept in mind accordingly in cases where
      other common causes of this rash are ruled out.

PMID- 22606524
TI  - Premature birth with complicated perinatal course delaying diagnosis of prader
      willi syndrome.
AB  - Prader-Willi syndrome in the newborn is essentially characterized by marked
      hypotonia, feeding difficulties, hypogonadism, and possible characteristic facial
      features. However, diagnosis at this age may be particularly difficult, and
      dysmorphic features may be subtle or absent. Prematurity can furthermore delay
      clinical features recognition and typical complications due to preterm birth may
      contribute to divert the diagnosis. We describe a preterm baby with a complicated
      perinatal course later diagnosed as PWS.

PMID- 22606525
TI  - Congenital infiltrating lipomatosis of the face: a case report.
AB  - Congenital infiltrating lipomatosis of the face is a rare lesion that comprises a
      subgroup of lipomatous tumor-like lesions of infancy and childhood. It is
      characterized by (1) no encapsulation, (2) diffuse infiltration of mature adipose
      tissue over normal muscle fiber and surrounding structures of face, (3) osseous
      hyperplasia of subjacent bone, and (4) a high recurrence rate. We report a case
      of a nine-month-old infant who presented with swelling over right face since
      birth. Early diagnosis of this lesion provides better surgical approach to
      control the infiltrative nature of its growth with recurrence and aesthetic
      appearance.

PMID- 22606526
TI  - Necrobiosis lipoidica diabeticorum.
AB  - Necrobiosis lipoidica is a rare disorder that usually appears in the lower
      extremities and it is often related to diabetes mellitus. There are few reported
      cases of necrobiosis lipoidica in children. We present an interesting case in
      that the patient developed lesions on the abdomen, which is an unusual location.

PMID- 22606527
TI  - Prolonged leptospira urinary shedding in a 10-year-old girl.
AB  - We present a case of leptospirosis in a previously healthy girl following a trip
      to Costa Rica. While she was clinically asymptomatic, she had spirochetes
      cultured from her urine six weeks following her trip. Prolonged urinary shedding
      following infection with Leptospira is possible in humans and often has subtle
      manifestations in children.

PMID- 22606528
TI  - Sensorineural Hearing Loss following Carbon Monoxide Poisoning.
AB  - A case study is presented of a 17-year-old male who sustained an anoxic brain
      injury and sensorineural hearing loss secondary to carbon monoxide poisoning.
      Audiological data is presented showing a slightly asymmetrical hearing loss of
      sensorineural origin and mild-to-severe degree for both ears. Word recognition
      performance was fair to poor bilaterally for speech presented at normal
      conversational levels in quiet. Management considerations of the hearing loss are
      discussed.

PMID- 22606529
TI  - Infantile hemangiomas masquerading as other periocular disorders.
AB  - Periocular tumors are common in infancy. The most common periocular tumors are
      capillary hemangiomas, which are present in 1-2% of newborns and develop in 10%
      12% of children by the age of 1 year old. Deep capillary hemangiomas may be more
      challenging to diagnose than superficial capillary hemangiomas and can be
      confused with other orbital lesions. Deep orbital hemangiomas can mimic teratoma,
      lymphangioma, rhabdomyosarcoma, metastatic neuroblastoma, and granulocytic
      sarcoma. In this paper, we describe 2 pediatric cases where previously diagnosed
      dermoid cyst and dacrocystocele were found to be capillary hemangiomas upon
      biopsy. Approaches to distinguish capillary hemangiomas from other periocular
      tumors are further discussed. To our knowledge, this is the first case report of
      periocular hemangiomas imitating a dermoid cyst and a dacrocystocele. These cases
      emphasize the importance of including infantile hemangiomas in the differential
      diagnosis of subcutaneous periocular abnormalities.

PMID- 22606530
TI  - Pneumoperitoneum in a Micropremie: Not Always NEC.
AB  - Pneumoperitoneum in the newborn is an acute surgical emergency requiring
      immediate surgical intervention to ensure survival. It refers to radiological
      evidence of rupture of an air-containing viscus with resultant soiling of the
      peritoneal cavity. A female baby was born preterm at 29 weeks with birth weight
      of 650 grams. She developed abdominal distension on day 6, and abdominal
      radiography revealed presence of free air in the peritoneum. She proceeded for a
      laparotomy, and intraoperative findings revealed blood in the peritoneum with an
      area of inflammation and a small perforation. About 5 cm of the inflamed bowel
      was resected, and an end to end anastomosis performed. The histopathology of the
      specimen was consistent with Meckel's diverticulum. Symptomatic Meckel's
      diverticulum is usually seen in the first two years of life, and perforation is a
      rare presentation. Perforated Meckel's diverticulum in a premature newborn is
      very rare, and a review of literature reveals only one other reported case.
      Newborn Meckel's perforation cases often mimic necrotizing enterocolitis,
      although many present without any feature of peritonitis. Establishing a
      preoperative diagnosis of perforated Meckel's is difficult and may not be
      essential as the treatment remains the same. However, prompt surgical
      intervention confers a good prognosis in neonates with isolated perforated
      Meckel's diverticulum.

PMID- 22606531
TI  - Tracheostomy wound myiasis in a child: case report and review of the literature.
AB  - An 8-year-old tracheostomized, gastrostomized, and with cerebral palsy boy was
      admitted for tracheostomy wound myiasis and cellulitis. Ether was applied in the
      wound, and then all the accessible larvae were removed. Antibiotic therapy was
      initiated. The procedure had to be repeated three more times to extract all the
      larvae. An airway endoscopy was performed and ruled out the presence of larvae in
      the airway, as well as any damage to the wall of the trachea. The patient
      recovered uneventfully and was discharged.

PMID- 22606532
TI  - Seatbelt: a double-edged sword.
AB  - Intra-abdominal vascular injury due to blunt trauma is unusual in children. Due
      to its rarity, detailed reports dealing with its management are scarce in
      paediatric literature. Diagnosis of these injuries is challenging, and a high
      degree of awareness is necessary for rapid identification and treatment of these
      injuries. We report the case of a child with seatbelt sign and mesenteric vein
      injury due to blunt trauma to the abdomen during a motor vehicle accident where
      the seatbelt was incorrectly placed. She also sustained cervical vertebral
      injury. The pattern of injuries in children in these situations may differ from
      that found in adults. While seatbelts have undoubtedly saved many lives,
      awareness about correct placement of these restraints is extremely necessary.

PMID- 22606533
TI  - Two case reports of familial chylomicronemia syndrome.
AB  - Familial chylomicronemia is a rare autosomal recessive disorder which is also
      called Hyperlipoproteinemia type I. Here we report two cases with this rare
      disorder that were admitted to our hospital in recent years.

PMID- 22606534
TI  - Acute Muscle Trauma due to Overexercise in an Otherwise Healthy Patient with
      Cystic Fibrosis.
AB  - Cystic fibrosis (CF) is one of the most common inherited diseases and is caused
      by mutations in the CFTR gene. Although the pulmonary and gastrointestinal
      manifestations of the disease remain in the focus of treatment, recent studies
      have shown expression of the CFTR gene product in skeletal muscle cells and
      observed altered intramuscular Ca(2+) release dynamics in CFTR-deficient animal
      models. Physical exercise is beneficial for maintaining fitness and well-being in
      CF patients and constitutes one aspect of modern multimodal treatment, which has
      considerably increased life span and reduced morbidity. We report on a case of
      acute muscle trauma resulting from excessive dumbbell exercise in a young adult
      with cystic fibrosis and describe clinical, laboratory and imaging
      characteristics of acute exercise-induced muscle injury.

PMID- 22606535
TI  - Localized acquired hypertrichosis associated with the application of a splint.
AB  - We describe a 16-year-old boy whose left forearm and hand were cut by a piece of
      glass from a broken window as a result of the fall. He had surgical repair of his
      left extensor pollicis brevis, abductor pollicis brevis, and dorsal branch of the
      left radial nerve. Following the surgery, he was put on a splint so as to
      immobilize the left forearm and wrist. On removal of the splint 4 weeks post
      surgery, he was noticed to have more hair growth on his left forearm and hand
      than his right counterparts. The patient was reassessed 2, 4, and 8 months after
      the removal of the splint. The hypertrichosis got better with time. At the last
      visit, the hair growth in the left forearm and hand was back to normal. Our
      patient represents the first reported case of localized acquired hypertrichosis
      following the application of a splint in the pediatric literature.

PMID- 22606536
TI  - A dysmorphic child with a pericentric inversion of chromosome 8.
AB  - An 8-year-old boy was referred to our institute with dysmorphic features such as
      mild lupus, micrognathia, low hair line, hypoplasia, hemi atrophy of left side of
      the face, abnormal size of ears, hypothenar, hypoplasia of chin, and tongue tie.
      MRI scan was found to be normal and EEG suggestive of generalized seizure
      disorder. Cytogenetic evaluation of the proband revealed a pericentric inversion
      of chromosome 8 with 46, XY, and inv 8 (p11.2; q21.2) karyotype.

PMID- 22606537
TI  - Primary maxillofacial large B-cell lymphoma in immunocompetent patients: report
      of 5 cases.
AB  - Lymphomas of the oral cavity represent 5% of all lymphomas. They usually occur in
      immunocompromised patients. Lymphoma arising within a single bone, without
      visceral or lymph node involvement, is known as primary intraosseous lymphoma. It
      is a rare condition and constitutes 3.1% of malignant bone tumors and 5% of
      extranodal lymphomas. Primary lymphoma of the jaw is seldom seen and it is often
      misdiagnosed. Clinically, the manifestations are usually similar to an
      odontogenic tumor, cyst, or infection. Radiographically it appears as a
      radiolucent area that may mimic endodontic lesion, periodontal pathology, or
      odontogenic cyst or tumor. The initial presentation is commonly followed by
      multiple unnecessary extractions and/or root canal treatments. We present five
      cases of rare primary lymphoma of the maxillofacial complex, four of them
      intraosseous.

PMID- 22606538
TI  - Pulmonary artery aneurysm as a cause of massive hemoptysis: diagnosis and
      management.
AB  - Massive hemoptysis is a life-threatening medical emergency. Prompt radiological
      diagnosis and management are essential. I present a case of an inflammatory
      pulmonary aneurysm (Rasmussen aneurysm) from active pulmonary tuberculosis. This
      is an uncommon cause for massive hemoptysis which was successfully treated by
      endovascular coiling.

PMID- 22606539
TI  - Conquering mount fuji: resolution of tension pneumocephalus with a foley urinary
      catheter.
AB  - Tension pneumocephalus is the presence of air or gas in the cranium that is under
      pressure. It occurs due to disruption of the skull, including trauma to the head
      or face, after neurosurgical procedures and occasionally, spontaneously (Schirmer
      et al., 2010). Patients typically present with headache but can also have
      neurological deficits such as decreased mental status, numbness, and weakness
      (Schirmer et al., 2010). It is diagnosed by computerized tomography (CT) scan
      (Michel, 2010). The characteristic finding is that the two frontal poles of the
      brain are separated by air. After diagnosis, treatment is imperative for both
      symptomatic relief and preventing further compression. We present a case of a
      patient who presented with tension pneumocephalus and unconventional treatment
      that resulted in clinical improvement of his symptoms and radiographic resolution
      of his condition.

PMID- 22606540
TI  - Prolonged Intestinal Mucosal Barium Coating due to Ischemic Necrosis.
AB  - A case of a 63-year-old man with small bowel ischemia six weeks after
      transplantation surgery is presented. Plain abdominal radiograph obtained several
      days after ingestion of barium shows the sign of prolonged barium coating
      indicating severe mucosal damage. Abdominal CT scan demonstrates small bowel wall
      thickening as well as pockets of peritoneal fluid collections. Most critically,
      CT allows visualization of subtle traces of dense barium within the dependent
      portions of this fluid indicating bowel perforation.

PMID- 22606542
TI  - Retroperitoneal malignant fibrous histiocytoma can mimic a hydatid cyst.
AB  - Malignant fibrous histiocytoma is the second most common soft-tissue sarcoma in
      adults. After the extremities, the retroperitoneal space is the second most
      common site of this tumor. A 50-year-old man presented with a right
      retroperitoneal, thick-walled, cystic multilocular mass measuring 10 * 10 cm that
      was thought to be a type CE 5 hydatid cyst preoperatively. However, the
      postoperative histopathology did not agree with the radiological findings and
      instead showed a malignant fibrous histiocytoma. The computed tomography and
      ultrasound/Doppler ultrasound findings of this retroperitoneal mass mimicked a
      type CE 5 hydatid cyst. We present this case because the surgical management of
      these two lesions differs and misdiagnosis can be problematic.

PMID- 22606541
TI  - Complications using bioabsorbable cross-pin femoral fixation: a case report and
      review of the literature.
AB  - The use of bioabsorbable cross-pin transcondylar fixation has remained a viable
      option for femoral fixation in anterior cruciate ligament reconstruction.
      Although numerous biomechanical studies have demonstrated high fixation strength
      and minimal slippage with use of this method of fixation, there have been
      increasing reports of a variety of clinical complications associated with these
      implants. We reviewed the literature for all complications associated with the
      Bio-TransFix implant and present a case report of a patient status after ACL
      reconstruction using Bio-TransFix cross-pin femoral fixation with iliotibial band
      friction syndrome from a broken cross-pin four month post-operatively.

PMID- 22606543
TI  - (1)H MR Spectroscopy in Gliomatosis: Is there a Sensitivity Issue?
AB  - Objective. (1)H MR spectroscopy (MRS) is widely performed for assessment of brain
      tumours and is considered a highly sensitive technique capable of differentiating
      benign from malignant conditions and tumour grading. Method. We present a case of
      a 69 year old woman who was suspected to have gliomatosis on MRI. Results. MRS
      performed using single voxel and chemical shift/multivoxel techniques was within
      normal limits. A repeat scan 6 months later showed progressive disease, and
      biopsy was performed that proved the diagnosis of glioblastoma. Conclusion.
      Normal MRS in a patient with suspicion of gliomatosis on MRI should not reassure
      clinicians into assuming a benign aetiology or a good prognosis in short term.

PMID- 22606544
TI  - Uterine artery pseudoaneurysm in the setting of delayed postpartum hemorrhage:
      successful treatment with emergency arterial embolization.
AB  - Postpartum hemorrhage is a major cause of maternal mortality. Though uncommon,
      uterine artery pseudoaneurysm can follow uterine dilatation and curettage (D + C)
      and needs to be considered in the differential diagnosis. This 30-year-old G1P1
      woman presented with right upper quadrant pain and vaginal bleeding. She was
      afebrile but her white blood count was significantly increased (22.2 * 10(9) /L).
      One week prior, she had undergone a Cesarean delivery which was complicated by
      hemolysis, elevated liver enzymes, and low platelet count syndrome (HELLP), fetal
      dystocia, and chorioamnionitis. Uterine dilatation and curettage (D & C) and
      placement of a Bakri intrauterine balloon, performed for suspected retained
      products of conception, failed to control her postpartum bleeding. The patient
      wished to have a hysterectomy only as a last resort in order to preserve
      fertility. Emergency uterine artery angiography revealed a left uterine artery
      pseudoaneurysm and contrast extravasation. The patient was successfully treated
      with selective embolization. Computed tomography (CT) later revealed dehiscence
      of her uterine Cesarean section incision with an intra-abdominal fluid
      collection. This collection was drained. She also developed disseminated
      intravascular coagulopathy (DIC) syndrome as well as multiple pulmonary emboli
      which were both successfully treated. We discuss this unique case of uterine
      artery pseudoaneurysm with associated uterine dehiscence.

PMID- 22606545
TI  - Brown tumor as a result of hyperparathyroidism in an end-stage renal disease
      patient.
AB  - A 49-year-old male with known history of end-stage renal disease (ESRD) presents
      with an intraoral exophytic mass of the right mandible. This lesion was given a
      histologic diagnosis of a Brown tumor. Purpose. To allow physicians to include
      this lesion in a differential diagnosis when evaluating patients with primary,
      secondary, or tertiary hyperparathyroidism.

PMID- 22606546
TI  - Porcelain atrium: a case report with literature review.
AB  - Massive left atrial wall calcification, or porcelain atrium, is very rare. We
      describe a case of an unusual pattern of cardiac calcification demonstrated on
      routine preoperative chest X-ray for cataract surgery in a 71-year-old Nigerian
      woman. Past medical history was significant for mitral stenosis and atrial
      fibrillation. Radiographic imaging revealed curvilinear high density areas of
      calcification outlining the left atrium on the chest X-ray. Noncontrast CT scan
      of the thorax confirmed the left atrial distribution of calcification and, thus,
      the diagnosis of porcelain left atrium.

PMID- 22606547
TI  - Chronic iliac vein occlusion and painful nonhealing ulcer induced by high venous
      pressures from an arteriovenous malformation.
AB  - Chronic femoral vein compression (May-Thurner Syndrome) is a known rare cause of
      deep venous thrombosis. Subsequent angiogenesis and the development of
      arteriovenous malformation (AVM) in the setting of chronic venous thrombosis is
      by itself a rare and poorly understood phenomenon. We report a case in which
      elevated venous pressures resulting from such compression appear to have resulted
      in the development of a pelvic arteriovenous malformation, which was further
      complicated by chronic, nonhealing painful lower extremity ulcers, and the
      development of extensive subcutaneous venous collaterals. Following successful
      embolization of the pelvic AVM and ablation of veins under the ulcers with laser
      and sclerotherapy, the patient's ulcers healed and she became pain-free.

PMID- 22606548
TI  - Rupture of the distal biceps tendon combined with a supinator muscle tear in a 51
      year-old woman: a case report.
AB  - Distal biceps tendon rupture is a relatively uncommon occurrence in the general
      female population, and to our knowledge, has not been reported in association
      with a supinator muscle tear. We report a case of 51-year-old woman who
      experienced sharp pain in her forearm and elbow after lifting a heavy object.
      History and physical examination raised suspicion for a distal biceps tendon
      rupture. MRI imaging determined a combined distal biceps tendon tear with a
      supinator muscle tear with subsequent confirmation at surgery. Surgical repair
      was performed for the distal biceps tendon only through a single incision
      approach using the Endobutton technique.

PMID- 22606549
TI  - Embolisation of posttraumatic superior mesenteric artery pseudoaneurysm in a
      patient with short bowel syndrome preceding bowel transplantation.
AB  - Penetrating abdominal trauma often causes bowel injuries which may lead to "short
      bowel syndrome" which is a potential indication for bowel transplantation.
      Posttraumatic pseudoaneurysms of abdominal arteries are often a result of
      penetrating abdominal trauma. We report a successful embolisation of
      posttraumatic superior mesenteric artery (SMA) branch pseudoaneurysm using
      microcoil, in a patient with short bowel syndrome who was successfully
      transplanted three months after embolisation.

PMID- 22606550
TI  - Intra-abdominal testicular seminoma in a woman with testicular feminization
      syndrome.
AB  - We report a case of intra-abdominal testicular tumor in a 36-year-old married
      lady presenting with chief complaints of primary amenorrhea. The patient was
      later diagnosed with testicular feminization syndrome, a form of male
      pseudohermaphroditism. This testicular tumor was histologically proven as
      seminoma. Due to rarity, imaging findings in patients with testicular
      feminization syndrome and intraabdominal testicular tumor have been poorly
      documented. So far, only one case report had described the combined role of CT
      and MR imaging in intraabdominal testicular sex-cord stromal tumor. To our
      knowledge, this case is first to document USG and MR imaging in addition to MR
      spectroscopy features in intraabdominal testicular seminoma.

PMID- 22606551
TI  - Adrenal Hemangioma: Findings at Multidetector CT with Short Review of the
      Literature.
AB  - We present the computed tomography (CT) imaging findings of a 44-year-old male
      with incidentally discovered right adrenal hemangioma displaying imaging pattern
      of nonadenomatous pattern, associated with multiple hepatic hemangiomata using 64
      slice multidetector scanner with reviewing published CT imaging findings with
      short review of the literature.

PMID- 22606552
TI  - 3D Imaging in Unilateral Primary Pulmonary Hypoplasia in an Adult: A Case Report.
AB  - Unilateral primary pulmonary hypoplasia is rare in adulthood (UPHA); it is
      characterized by a decreased number of bronchial segmentation and
      decreased/absent alveolar air space. Classical chest X-ray may be confusing, and
      the biological tests are unspecific. We present a case of UPHA in a 60-year-old
      female, smoker, with 3 term normal deliveries, who presented with late recurrent
      pneumonias and bronchiectasis-type symptomathology, arterial hypertension, and
      obesity. Chest X-rays revealed opacity in the left lower pulmonary zone, an
      apparent hypoaerated upper left lobe and left deviation of the mediastinum.
      Preoperatory multidetector computer tomography (MDCT) presented a small
      retrocardiac left lung with 5-6 bronchial segmentation range and cystic
      appearance. After pneumonectomy the gross specimen showed a small lung with
      multiple bronchiectasis and small cysts, lined by hyperplasic epithelium,
      surrounded by stromal fibrosclerosis. We concluded that this UPHA occurred in the
      4-7 embryonic weeks, and the 3D MDCT reconstructions offered the best noninvasive
      diagnosis.

PMID- 22606553
TI  - Co-registration of Sequential Multidetector Computed Tomography Studies for the
      Evaluation of Surgical Instrumentation following Resection of Spinal Tumors.
AB  - Surgical resection of spinal tumors involves complex reconstructive procedures.
      The stability and integrity of the surgical construct are evaluated with
      multidetector computed tomography (MDCT). As coregistration, or fusion, of
      different imaging modalities, especially positron emission tomography/computed
      tomography (PET/CT), is common practice, we sought to determine if this technique
      could be applied to sequential, postoperative MDCT studies of the spine. Herein,
      we demonstrate that by utilizing the Hermes workstation, co-registration of MDCT
      spine studies can be performed. This technique allows sequential MDCT
      examinations of the post-operative spine to be viewed together as one study and
      may aid in evaluation of the position and integrity of the surgical construct
      over time. Further study and refinement of this technique will be necessary
      before clinical implementation.

PMID- 22606555
TI  - Organizing pneumonia by paragonimiasis and coexistent aspergilloma manifested as
      a pulmonary irregular nodule.
AB  - Organizing pneumonia by paragonimiasis and coexistent aspergilloma as a pulmonary
      nodule is a rare case of lung disease. Its radiographic or CT feature has not
      been described before in the radiologic literature. We present organizing
      pneumonia by paragonimiasis and coexistent aspergilloma manifested as a pulmonary
      irregular nodule on CT.

PMID- 22606554
TI  - Imaging of a case of extramedullary solitary plasmacytoma of the trachea.
AB  - We describe a case of extramedullary tracheal plasmacytoma that was incidentally
      discovered in a 73-year-old man on a PET scan performed for assessing the extent
      of colon cancer. CT scan showed the tumor; multiplanar reformation coupled with
      virtual bronchoscopy allowed proper treatment planning. The tracheal tumor was
      resected during rigid bronchoscopy. Relevant investigations excluded multiple
      myeloma. Follow-up CT showed persistent thickening of the tracheal wall, but
      there has been no recurrence after one-year followup.

PMID- 22606556
TI  - CMR Features in Cardiac Sarcoidosis.
AB  - Sarcoidosis is a multisystemic disorder of unknown aetiology characterised by the
      formation of noncaseating epithelioid cell granuloma involving various organ
      systems. Cardiac involvement has an important prognostic factor as it can present
      with life-threatening arrythmias and sudden death. Here, we present a case of
      cardiac sarcoidosis in a 46-year-old gentleman who presented with nonspecific
      signs and symptoms. We also discuss diagnostic difficulties especially when
      cardiac involvement is the only clinical sign. In this case, cardiac magnetic
      resonance (CMR) played an important role in the diagnosis and followup of our
      patient.

PMID- 22606557
TI  - Gossypiboma versus Gossip-Boma.
AB  - Gossypiboma, or a retained surgical sponge, is a rare condition, and it can occur
      after any surgical intervention that requires use of internal swabs. A case of an
      eight-year-old girl is presented, who had right minithoracotomy for ASD closure.
      She was finally diagnosed to have a retained surgical sponge in the right pleural
      cavity.

PMID- 22606558
TI  - Multifocal dysembryoplastic neuroepithelial tumour with intradural spinal cord
      lipomas: report of a case.
AB  - We report a case of temporal lobe epilepsy and incomplete Brown-Sequard syndrome
      of the thoracic cord. Computed tomography and magnetic resonance (MR) imaging
      showed multiple supratentorial masses with the classical radiological appearances
      of multifocal dysembryoplastic neuroepithelial tumour (DNET). Spinal MR imaging
      revealed intradural lipomas, not previously reported in association with
      multifocal DNET. Presentation and imaging findings are discussed along with
      classification and natural history of the tumour.

PMID- 22606559
TI  - Catheter fracture and embolization related to an arm venous port.
AB  - This 55-year-old female had a chest X-ray during a follow-up visit for the
      management of her breast cancer. The chest X-ray demonstrated an embolized venous
      catheter superimposed upon the mediastinum. It was determined that the catheter
      of the patient's arm port had fractured and embolized to the pulmonary
      circulation. The catheter was retrieved, in the interventional radiology suite,
      under fluoroscopic guidance. The patient suffered no ill effects. Subsequently,
      one day later, the old vein port was removed and a new arm port and associated
      catheter were implanted to facilitate the delivery of the patient's ongoing
      chemotherapy.

PMID- 22606560
TI  - A "Near-Miss Lethal Accident Case" in MR Suit of a Tertiary Care Hospital.
AB  - A "near miss" is an unpleasant event that did not result in injury, illness, or
      damage but had the potential to do so, but for a fortunate break in the chain of
      events. We present a near-miss case which occurred in the MR suite of a tertiary
      care hospital. Although the MR is considered a very safe procedure, if MR safety
      guidelines are not adhered to, adverse and catastrophic events to the extent of
      patient deaths are known to have occurred. It is hoped that this incident will
      prompt hospitals to document and follow MR safety protocols for patient and staff
      safety. Although MRI is an extremely safe procedure rarely MR adverse incidents
      have resulted in serious physical injury or even death. The incident is an eye
      opener regarding potential adverse events lurking in the relatively safe MR
      environment and provides an opportunity to rectify the inadequacies in MR safety.

PMID- 22606561
TI  - Retrograde Ureteric Stents via an Ileal Conduit.
AB  - Patients having undergone pelvic exenteration with urinary diversion can present
      with short- and long-term complications such as ureteral strictures, anastomotic
      leakage, calculi, or fluid collections (abscess, urinoma, lymphocele, or
      hematoma). A dehiscence resulting in a perineal urinary fistula is an uncommon
      late complication of urinary diversion surgery; surgical treatment for this
      complication is less desirable because of postsurgical or radiation-induced
      pelvic changes that can occur. As a result, nephrostomy or antegrade stenting of
      the kidneys is more viable. Retrograde ureteric stent insertion is discussed in
      relation to a patient suffering from ileal conduit dehiscence. The presence of
      these stents probably helped diminish the potential for complications during
      subsequent nephrostomy tube insertion.

PMID- 22606562
TI  - Massive hematochezia: a complication of methamphetamine-induced vasculitis
      treated by transcatheter hemostasis.
AB  - A long-term, heavy methamphetamine user with life-threatening rectal hemorrhage
      was treated with transcatheter occlusion of the bleeding arteries. The bleeding
      blood vessels were vulnerable submucosal arteries, part of the collateral supply
      to the distal colon. Visceral arteriography demonstrates severe arterial stenotic
      lesions of the celiac axis, superior mesenteric artery and the inferior
      mesenteric artery. Collateral vessels were seen with corkscrew morphology similar
      to that seen with thromboangiitis obliterans.

PMID- 22606563
TI  - Pseudoaneurysm of Lumbar Artery following a Vertebral Biopsy: A Case Report.
AB  - A 74-year-old man developed a severe low back pain and a fever. In the initial
      examinations, a collapse of the L5 anterosuperior vertebral body and narrowing of
      the L4/5 disc space were identified on radiographs, and the laboratory data
      showed inflammatory results. A computed tomography (CT) and a magnetic resonance
      imaging showed collapse of L5. A needle biopsy was performed to make a diagnosis;
      however, an abdominal pain and a hypotension appeared after the biopsy. An
      abdominal CT showed a hematoma in the retroperitoneal space, and an angiography
      revealed a left fourth lumbar artery pseudoaneurysm. The pseudoaneurysm was
      treated with transcatheter placement of microcoils. Although haemorrhagic
      complications following needle biopsy are very rare, patients with large amounts
      of vertebral destruction may have unusual anatomical positions of the lumber
      artery. Therefore, surgeons should be aware of the possibility of lumbar artery
      injury during a needle biopsy and take care of prebiopsy plans.

PMID- 22606564
TI  - Brooke-spiegler syndrome with multiple scalp cylindromas and bilateral parotid
      gland adenomas.
AB  - A 62-year-old female presented with numerous soft tissue lesions of her scalp and
      bilateral preauricular region. Several of these have been biopsied or removed
      with a diagnosis of cylindromas. Cylindromas are benign tumors with a
      differentiation towards apocrine sweat glands that increase in number and size
      throughout life. Multiple scalp cylindromas may coalesce and cover the entire
      scalp, resulting in the "turban tumor." These are often associated with the
      autosomal dominant Brooke-Spiegler syndrome with coexistent facial
      trichoepitheliomas and spiradenomas. There is a very rare association between
      cylindromas and basal cell adenoma and adenocarcinoma of the parotid gland, with
      only 17 reported cases. Ours is the first CT demonstration of both the scalp and
      parotid gland findings in this uncommon situation.

PMID- 22606565
TI  - Misdiagnosed uterine rupture of an advanced cornual pregnancy.
AB  - Cornual pregnancy is a diagnostic and therapeutic challenge with potential severe
      consequences if uterine rupture occurs with following massive intraabdominal
      bleeding. We report a case of a misdiagnosed ruptured cornual pregnancy occurring
      at 21 weeks of gestation. Ultrasound examination and computer tomography revealed
      no sign of abnormal pregnancy. The correct diagnosis was first made at emergency
      laparotomy. Uterine rupture should be considered in pregnant women presenting
      with abdominal pain and haemodynamic instability.

PMID- 22606566
TI  - A Complete Constellation of Nervous System Lesions of NF2: Imaging Evaluation.
AB  - The radiological findings fulfilling the criteria of neurofibromatosis type 2
      (NF2) were reviewed. NF2 is a rare disease with few cutaneous but frequent,
      typical radiological findings in the central nervous system. The presenting
      symptom is most commonly hearing loss due to acoustic schwannomas, although
      symptoms emanating from other intracranial or tumors are not uncommon. The
      discovery of multiple spinal neurofibromas or multiple meningiomas without
      cutaneous lesions should initiate a search for acoustic schwannomas even when the
      patient has normal hearing as in our case patient who actually presented for
      weakness of all four limbs.

PMID- 22606567
TI  - Case study: chronic recurrent multifocal osteomyelitis in the femoral diaphysis
      of a young female.
AB  - Chronic recurrent multifocal osteomyelitis (CRMO) is relatively uncommon. Even
      though the name suggests it is the result of infection, this is not likely the
      case. Instead it is more likely the result of genetic, autoimmune, or
      autoinflammatory causes. Although CRMO has a benign course and responds well to
      anti-inflammatory medications, it can have a very aggressive clinical and imaging
      presentation overlapping with infectious osteomyelitis and malignancy. Therefore,
      radiologists and clinicians need to be aware of its clinical and imaging
      presentation to avoid morbidity associated with more aggressive treatment. We
      present the case of a ten-year-old female with CRMO as a solitary expansile-mixed
      lytic and sclerotic lesion in the distal femoral diaphysis. The diaphyseal
      location and mixed lytic and sclerotic appearance are less common and have an
      aggressive imaging appearance. We also review the pathophysiology, imaging
      findings, and therapeutic approach to this uncommon but clinically important
      condition.

PMID- 22606568
TI  - Case report: recognizing pneumatosis intestinalis: a case of bowel ischemia
      presenting as renal colic.
AB  - The clinical diagnosis of bowel ischemia is often difficult and the diagnosis can
      easily be missed unless there is a high index of clinical and radiological
      suspicion. Bowel ischemia and or infarction must be considered in the
      differential diagnosis in the older patient with pre-existing coronary artery or
      generalized vascular disease, cardiac failure, or arrhythmias especially atrial
      fibrillation and hypertension. An elderly patient with caecal infarction is
      presented who was initially diagnosed and treated for renal colic.

PMID- 22606569
TI  - Multiple FNH-Like Lesions in a Patient with Chronic Budd-Chiari Syndrome: Gd-EOB
      Enhanced MRI and BR1 CEUS Findings.
AB  - A-26-year old female patient with chronic Budd-Chiari syndrome due to different
      underlying blood disorders applied for a two-year followup of the liver with
      Gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic-acid-(Gd-EOB-DTPA-)
      enhanced MRI. The liver function tests were raised. Besides showing a progressive
      hepatosplenomegaly and a cirrhotic liver alteration, the MRI revealed multiple
      new nodular lesions in all liver segments. These lesions showed typical patterns
      in the precontrast images, while there was an arterial and a persistent portal
      venous enhancement. In the hepatobiliary liver-specific late phase, a central
      "washout" and a persistent rim enhancement were observed (target sign). The
      additionally performed contrast-enhanced ultrasonography showed a strong
      zentrifugal arterial enhancement of the lesions followed by an isoechoic
      enhancement in the portal venous and delayed liver phase. Histologically these
      lesions turned out as focal nodular hyperplasias (FNH) or FNH-like lesions, also
      known as large regenerative nodules (LRNs). Differentiation between regenerative
      nodules like LRN and hepatocellular carcinoma (HCC) in cirrhotic livers is
      crucial, and the target sign in the hepatobiliary phase of Gd-EOB-DTPA as well as
      the centrifugal arterial enhancement followed by an isoenhancement during a CEUS
      might be useful for establishing the correct diagnosis of such hypervascular
      lesions with proliferated and likely aberrant bile ducts.

PMID- 22606570
TI  - Arterial microcalcifications in the breast mimicking malignancy.
AB  - Microcalcifications in the breast are highly suggestive of malignancy; they can
      occur in many pathological conditions. A 36-years-old nondiabetic woman came to
      the gynaecologist with a suspect palpable mass in the upper outer quadrant of the
      right breast. Histopathological examination confirmed a calcification of a small
      artery (diameter: 0.45 mm). Arterial calcifications can mimic a malignant lesion
      in the breast.

PMID- 22606571
TI  - Oncoplastic surgery in Japanese patients with breast cancer close to the areola:
      partial mastectomy using periareolar mammoplasty: a case report.
AB  - We report the results of oncoplastic surgery in two Japanese patients with early
      breast cancer. Their breasts were large and ptotic, and their lesions, which were
      close to the areola, were considered to be suitable for breast conservative
      surgery. Oncoplastic surgery involving partial resection of the gland and a
      periareolar mammoplasty were performed. The technique was easy to perform, and
      the cosmetic outcome was excellent.

PMID- 22606572
TI  - Isolated cervical rib fracture: a rare etiology of thoracic outlet syndrome.
AB  - Isolated fracture of a cervical rib is a very rare entity and usually presents as
      a painless swelling or as thoracic outlet syndrome. We describe a case of a 45
      year-old woman with history of fall two months back. She presented with symptoms
      of neurogenic thoracic outlet syndrome for one month. Isolated left cervical rib
      fracture was documented on X-ray cervical spine. Her fractured cervical rib was
      resected through a supraclavicular approach, and symptoms resolved completely in
      the postoperative period.

PMID- 22606573
TI  - Congenital intranasal glioma.
AB  - Congenital midline swellings of nose are encountered rarely, and nasal gliomas
      constitute about 5% of such lesions. Various theories have been suggested to
      explain the pathogenesis. Imaging preferably by MRI is mandated to study the
      extent and to rule out intracranial extension. Treatment is complete excision,
      and the approach depends upon the extent of the lesion and availability of
      expertise. We present the management of one such case of congenital intranasal
      glioma without any intracranial extension that presented as a septal polyp.

PMID- 22606574
TI  - Intrauterine contraceptive device migration presenting as abdominal wall
      swelling: a case report.
AB  - A number of complications are reported with the use of intrauterine contraceptive
      devices. These may pursue asymptomatic course or present as an acute abdomen
      after migration into peritoneal cavity. The authors here are reporting an
      abdominal wall swelling caused by transuterine migration of a copper intrauterine
      contraceptive device in a 28-year-old female. An open approach was used, and
      impacted foreign body was retrieved.

PMID- 22606575
TI  - Necrosis of the 4th and 5th digits after intra-articular injection of diazepam
      into the wrist.
AB  - A 75-year-old woman presented with progressing pain, cyanosis, and hypaesthesia
      in her left hand after an intra-articular injection with diazepam into the wrist
      for osteoarthritis-related pain. Due to an iatrogenic intra-arterial injection,
      malperfusion of the ulnar digits developed. Angiography revealed blockage of
      perfusion of the 4th and 5th digits. Despite intra-arterial lysis,
      heparinisation, and vasodilatation, perfusion could not be reinstalled. Necrosis
      of the distal phalanges of the 4th and 5th digits developed, which had to be
      treated with amputation. The pathomechanism of tissue damage and the treatment
      options after intra-arterial injections are reviewed and discussed.

PMID- 22606576
TI  - Glomus tumor of the stomach: a rare cause of upper gastrointestinal bleeding.
AB  - Introduction. Glomus tumors (GTs) are benign neoplasm originating from the glomus
      body, commonly described in subungual region. The involvement abdominal is rare.
      Our aim is to describe a case of glomus tumor of the stomach that presented upper
      gastrointestinal bleeding. A 34-year-old woman was admitted with upper
      gastrointestinal bleeding and underwent an upper endoscopy that showed bleeding
      arising from an ulcerated lesion, treated by sclerosis therapy. A new endoscopy
      confirmed a submucosal lesion in upper portion of the stomach. During the
      laparotomy, a tumor at the upper anterior wall of gastric body was found and
      resected by a vertical gastrectomy. The pathological exam revealed hyperplastic
      smooth muscle fibers of the muscularis propria of the stomach wall, surrounded by
      hyaline stroma. The immunohistochemistry panel was positive for smooth muscle
      actin and type IV collagen, with low rate of mitosis studied by Ki-67 which
      allowed the final diagnosis of a gastric glomus tumor. Discussion. The majority
      of intraperitoneal glomus tumors occur in the stomach, and it is phenotypically
      similar to those localized in peripheral sites. Gastric GT generally is a benign
      tumor although it can be malignant and have the potential to metastasize.
      Conclusion. Even though gastric glomus tumor is rarely described, it should be
      considered as a possible cause of a major upper gastrointestinal bleeding.

PMID- 22606577
TI  - Giant appendiceal leiomyosarcoma: a rare and unusual tumour.
AB  - Appendiceal tumours are uncommon but may be present in 0.9-1.4% of all
      appendicectomy specimens. While carcinoid tumours and adenocarcinomas comprise
      the majority of appendiceal tumours, rarely, lymphomas or sarcomas may also
      present in the appendix. Appendiceal leiomyosarcomas are rare, and to date, only
      a handful of cases have been reported. The current paper presents a case of giant
      appendiceal leiomyosarcoma followed by a review of the literature.

PMID- 22606578
TI  - Severe Vertex Epidural Hematoma in a Child: A Case Report of a Management without
      Expert Neurosurgical Care.
AB  - Vertex epidural hematomas (VEDHs) are an uncommon situation and difficulties may
      be encountered in their diagnosis and management. This is more complicated when
      the surgical management has to be performed by general surgeons, not specialized
      in neurosurgery, in a remote location. It was in this context that we were
      brought to care in charge a 2-year-old boy who required a neurosurgical emergency
      rescue for a severe VEDH in Djibouti. Through the description of this case, we
      want to emphasize the value of developing a network of teleconsultation for the
      benefit of remote and isolated locations and learning basic techniques of
      emergency neurosurgery.

PMID- 22606579
TI  - Spindle cell hemangioendothelioma of the temporal muscle resected with zygomatic
      osteotomy: a case report of an unusual intramuscular lesion mimicking sarcoma.
AB  - Spindle cell hemangioendothelioma (SCH) was originally described by Weiss and
      Enzinger (1986) as a low-grade angiosarcoma resembling both cavernous hemangioma
      and Kaposi's sarcoma. Recent studies suggest that SCH is a benign neoplasm or
      reactive lesion accompanying a congenital or acquired vascular malformation. Most
      SCHs present as one or more nodules affecting the dermis or subcutis of the
      distal extremities. Few reports describe SCH of the head and neck region; even
      fewer note intramuscular SCH. Here, we describe a case of SCH involving the
      temporal muscle mimicking soft tissue sarcoma, who had a successful surgical
      treatment with a coronal approach and zygomatic osteotomy.

PMID- 22606580
TI  - Laparoscopic diagnosis of incarcerated "spigelian hernia": report of a case and
      review of the literature.
AB  - Spigelian hernias are rare hernias, representing only about 1-2% of all abdominal
      hernias. An accurate preoperative diagnosis of this condition is often difficult
      because the physical presence of these hernias is often not demonstrable owing to
      its peculiar anatomic location. Many patients with Spigelian hernias, therefore,
      may have no obvious findings on clinical examination. The diagnosis is even
      trickier in obese patients wherein the hernia sac may lie in an intraparietal
      plane, masked by the abdominal subcutaneous fat. Here we describe a case of
      incarcerated Spigelian hernia where clinical and radiological findings were
      inconsistent and the accurate diagnosis was made by laparoscopy and was followed
      by a laparoscopic-assisted repair using an open anterior approach with an onlay
      mesh. We therefore feel that laparoscopy can be a useful tool for confirming the
      diagnosis and also for performing a definitive repair in doubtful cases of
      Spigelian hernias.

PMID- 22606581
TI  - Inflammatory pseudotumor of the liver complicated by lung necrosis and pleural
      empyema: a case report.
AB  - Inflammatory pseudotumor of the liver (IPTL) is a rare condition, but an
      important differential diagnosis of hepatic space-occupying lesions. It may
      regress spontaneously and mimic other liver tumors. Complications are usually
      intrahepatic. Herein, we present a case of IPTL which developed pleural empyema
      and lung necrosis as an uncommon complication.

PMID- 22606582
TI  - Unusual presentation of gastric perforation by foreign body: a case report.
AB  - Perforation of the gastrointestinal tract by ingested foreign body is rare. The
      majority of patients do not recall ingestion of the foreign body, and dietary
      foreign bodies are most commonly involved. We present an interesting case where
      the offending foreign body gave rise to a diagnostic dilemma masquerading as a
      pancreatic mass. A high index of suspicion is indicated especially when dealing
      with atypical presentation and nonspecific symptoms as highlighted in this case.

PMID- 22606583
TI  - An alternative surgical procedure for a patient with critically restenosed and
      kinked carotid artery: graft interposition.
AB  - According to the literature data, the prevalence of restenosis after carotid
      endarterectomy ranges between 6 and 36%. The etiological factor is intimal
      hyperplasia for early period, whereas it is atherosclerosis for late period. A 67
      year-old male patient admitted to our clinic with a history of headache and minor
      stroke. His medical history was significant for right carotid endarterectomy 8
      years ago. Recent Doppler ultrasound and digital substraction angiography
      revealed 75% stenosis and kinking corresponding to the segment distal to the
      endarterectomy region. Surgical endarterectomy is the treatment of choice in
      critical carotid stenosis. Endovascular therapy is primarily considered for
      patients if there is restenosis after carotid endarterectomy. However, the
      treatment modality is controversial in cases with concomitant carotid stenosis
      and kinking of internal carotid artery. We present our surgical approach to a
      case with significant stenosis and kinking of internal carotid artery. We
      performed a 6-mm-PTFE graft interposition between common and internal carotid
      artery and resection of the kinking segment.

PMID- 22606584
TI  - Multiply recurrent episodes of gastric emphysema.
AB  - Introduction. Gastric emphysema can present both a diagnostic challenge and a
      life-threatening condition for patients and has only once been reported as being
      recurrent. Background. A 64-year-old male presented with chronic abdominal pain
      and was found to have gastric pneumatosis on CT scan. The patient was
      successfully managed conservatively. The cause was attributed to aberrant
      arterial anatomy and atherosclerosis along with hypotension. The patient has
      since had 3 episodes of recurrent gastric emphysema, all managed nonoperatively.
      Discussion. To our knowledge, this is the first case of both serial episodes of
      gastric pneumatosis and gastric mucosal ischemia as a precipitating factor for
      the development of gastric emphysema.

PMID- 22606585
TI  - Primary synovial sarcoma of the mediastinum : a case report.
AB  - Synovial sarcomas commonly occur in the extremities of young adults. A primary
      occurrence in the mediastinum is very rare with only a few reported cases in the
      world literature. This paper is about a 42-year-old male who presented with chest
      pain and dyspnoea on exertion. Imaging showed an anterior mediastinal mass with
      adhesions to the lung. Pathological examination of the resected mass showed a
      biphasic neoplasm with a spindle cell component admixed with gland-like elements.
      The tumour showed positive staining with cytokeratin, epithelial membrane
      antigen, and Bcl-2 confirming the diagnosis of a biphasic synovial sarcoma. A
      wide range of neoplasms, both primary and metastatic, occur in the mediastinum,
      which pose considerable diagnostic difficulties. A synovial sarcoma should always
      be considered in the differential diagnosis, and immunohistochemistry is an
      important adjuvant tool in this situation. This paper highlights the importance
      of recognizing an unusual presentation of this aggressive neoplasm to aid
      appropriate clinical management.

PMID- 22606586
TI  - Localized advanced hurthle cell carcinoma with symptomatic intrathoracic goiter.
AB  - INTRATHORACIC GOITERS ARE DIVIDED INTO TWO CATEGORIES: primary and secondary.
      Intrathoracic goiters (IG) can cause upper airway obstruction. The presence of
      obstructive symptoms secondary to increased thyroid growth and tracheal
      compression is major indication for surgery; however, goiters do not always
      require immediate surgical attention. In addition, although some diagnostic tests
      indicate upper airway obstruction, many patients remain asymptomatic. Surgeries
      to remove IG are performed routinely however, they are not without risk. In some
      cases, intrathoracic goiters present as thyroid cancers. Very rare cancers such
      as Hurthle cell carcinoma (HCC) can create a challenge for the surgeon when
      surgical intervention is vital.

PMID- 22606587
TI  - Severe tracheobronchomalacia after prolonged intubation of multitrauma patient.
AB  - Tracheobronchomalacia is a condition with significant morbidity with many
      etiologies including iatrogenic ones and should be considered in critically ill
      ventilated trauma patients. We present a case of a multitrauma patient who had
      difficulty weaning from the ventilator after prolonged intubation followed by
      tracheostomy tube placement. We describe her presentation, diagnosis, and
      management provide and as well a discussion of the condition.

PMID- 22606588
TI  - Acute abdomen and perforated bowel with a rare pathology: nonfamilial visceral
      myopathy.
AB  - Visceral myopathy is a rare chronic disease affecting the peristalsis of the
      bowel causing intermittent pseudoobstruction. We report an atypical case of an
      eighty-nine-year-old woman with no prior history of abdominal illness who was
      admitted to our hospital with 2 days of increasing nausea, abdominal distension,
      and abdominal pain. On arrival at the hospital, she was critically ill. Abdominal
      X-ray showed distended loops of the colon and liquid levels resembling colonic
      obstruction. A subsequent abdominal CT scan confirmed the colonic obstruction. A
      suspicion of sigmoid volvulus was raised, that is why a barium enema was
      performed but no lower colonic obstruction could be confirmed. Acute laparotomy
      showed perforated cecum without intestinal obstruction. Postoperatively, the
      patient became septic which was fatal for the patient. Pathology gave the
      diagnosis visceral myopathy. It is very difficult to make the diagnosis
      clinically and radiologically since visceral myopathy mimics other more common
      gastrointestinal diseases. It is important to consider visceral myopathy as a
      possible diagnosis in cases with recurrent episodes of abdominal pain, vomiting,
      and abdominal distension, but without actual intestinal obstruction.

PMID- 22606589
TI  - Basidiobolomycosis of the colon masquerading as stenotic colon cancer.
AB  - Basidiobolus ranarum is a widespread saprophyte fungus with pathogenic potential.
      It affects mainly the subcutaneous tissues of the trunk and limbs. Relatively
      recently, occasional reports of gastrointestinal basidiobolomycosis appeared in
      the literature. Due to the rarity of the condition and the nonspecific presenting
      features, the correct diagnosis is usually hard to reach. In this paper, we
      describe the clinical course of an otherwise healthy female, who presented with a
      colonic mass. She received subtotal colectomy followed by oral itraconazole, with
      successful outcome.

PMID- 22606590
TI  - Megaloappendix: a case report.
AB  - The vermiform appendix is an organ that can have variable sizes, locations as
      well as functional potentials. We describe here the longest and largest appendix
      removed measuring about 55 cm in length.

PMID- 22606591
TI  - Ruptured hydatid cyst with an unusual presentation.
AB  - Ruptured pulmonary hydatid cyst may sometimes cause complications like empyema,
      bronchopleural fistula, and collapsed lung. These complications may mislead the
      diagnosis and treatment if prior evidence of cyst has not been documented before
      rupture. We present a case of a young male who presented with complete collapse
      of left lung with pyopneumothorax and bronchopleural fistula which was
      misdiagnosed as pulmonary tuberculosis. He was referred to us from peripheral
      hospital for pneumonectomy when his condition did not improve after six months of
      antitubercular chemotherapy and intercostals drainage. On investigation, CT scan
      revealed significant pleural thickening and massive pneumothorax restricting lung
      expansion. Decortication of thickened parietal and visceral pleura revealed a
      ruptured hydatid endocyst, and repair of leaking bronchial openings in floor of
      probable site of rupture in left upper lobe helped in the complete expansion of
      the collapsed lung followed by uneventful recovery.

PMID- 22606592
TI  - Correction of anophthalmic enophthalmos with a three-staged procedure: two case
      reports.
AB  - Surgical correction of an anophthalmic enophthalmos secondary to inappropriate
      repair of the eye socket involves several difficult aesthetic issues associated
      with long-term use of a poorly fitting prosthetic eye. In this paper, we present
      two cases of anophthalmic enophthalmos. During the treatment of the first
      patient, unsatisfactory cosmetic problems including lower eyelid retraction,
      hypoglobus, and severe upper eyelid ptosis were revealed. Accordingly, a three
      staged procedure was performed on the second patient, including autologous
      augmentation of the eye socket, correction of lower eyelid retraction with a
      cartilage graft, and a frontalis sling procedure to correct upper eyelid ptosis.

PMID- 22606593
TI  - Male breast cancer presenting as nipple discharge.
AB  - Male breast cancer (MBC) is a rare disease and constitutes less than 1% of all
      breast carcinoma cases. Although MBC most often presents with a palpable mass,
      failure to recognise the significance of other symptoms may lead to a delay in
      diagnosis. Nipple discharge (ND) is a rare symptom in men, but it may herald an
      underlying malignancy. We present two cases of (MBC) presenting with ND and
      emphasise the importance of this clinical sign in suspecting underlying
      malignancy and an opportunity for early diagnosis. We also discuss the clinical
      significance of ND in men in relation to current literature.

PMID- 22606594
TI  - Primary pelvic hydatid cyst: a case report.
AB  - This is a case report of a young man who presented to us as a case of hypogastric
      pain and frequency of micturation. General physical examination and radiological
      evaluation confirmed a multiloculated pelvic swelling. Patient was subjected to
      laparotomy which confirmed the diagnosis of a primary pelvic hydatid disease.
      Patient was put on chemotherapy after surgery and is doing well on follow up.

PMID- 22606595
TI  - Transabdominal Laparoscopic Repair of Amyand's Hernia: A Case Report.
AB  - The occurrence of appendicitis within an inguinal hernia, known as Amyand's
      hernia, is a rare condition. Laparoscopic approach to this type of hernia is not
      widely used, and there is little data comparing it to the open surgery approach.
      This article presents a case of Amyand's hernia treated successfully by
      laparoscopy via a transabdominal approach supported by a short review of
      literature on this rare condition.

PMID- 22606596
TI  - Endoscopic management of an internal laryngopyocele presenting with acute airway
      obstruction.
AB  - Statement of Problem. Laryngocele is a rare laryngeal disease, where there is an
      abnormal dilatation of the saccule of the laryngeal ventricle. It can either be
      internal or external, and a laryngopyocele is a rare complication of this
      anomaly. Internal laryngopyoceles can prove difficult to manage, as they often
      present with airway compromise. Method of Study. Case Report. Results. We present
      a case of a laryngopyocele that was successfully managed with suspension
      laryngoscopy and endoscopic marsupialisation and resection. To our knowledge,
      this is the first such case described in the literature. Conclusions. Surgical
      drainage of a laryngopyocele via the external approach is well documented in the
      literature. We feel that endoscopic resection of laryngopyoceles in an emergency
      situation is a viable alternative and also prevents the associated surgical
      morbidity.

PMID- 22606597
TI  - Emergent completion pneumonectomy for postoperative hemorrhage from rupture of
      the infected pulmonary artery in lung cancer surgery.
AB  - Completion pneumonectomy (CP) is one of the most difficult procedures and known
      to be associated with a high morbidity and mortality. A 74-year-old male
      underwent a left upper lobectomy for pulmonary adenocarcinoma (T3N0M0); six days
      later after the surgery, he had a sudden postoperative intrathoracic excessive
      hemorrhage with shock. Emergent redo thoracotomy was performed to treat the
      bleeding from the ablated interlobar pulmonary artery by suturing with prolene.
      However, 3 days later after the second operation, he had the second intrathoracic
      bleeding. Emergent CP was performed with cardiopulmonary bypass by anterior
      transpericarsial approach via a median sternotomy. The hemorrhage was caused by a
      rupture of the proximal fragile and infected pulmonary artery. We performed
      omentopexy for the infected intrathoracic cavity and for covering of the divided
      main bronchial stump. We had a rare experience of two times of postoperative life
      threatening hemorrhage from rupture of the infected pulmonary artery after left
      upper lobectomy. Emergent CP as salvage surgery should have an advantage in
      control of infected proximal pulmonary arterial hemorrhage. We should take care
      of tearing off of adventitia of pulmonary artery in lobectomy because of a
      possibility of postoperative hemorrhage under a fragility of the injured
      pulmonary artery with infection.

PMID- 22606598
TI  - Small bowel cocoon: a distinct disease with a new developmental etiology.
AB  - We have treated two patients with small bowel (abdominal) cocoon who presented
      with acute and partial small bowel obstruction associated with an abdominal mass.
      Neither had a history of previous surgery, peritonitis, or prolonged drug
      therapy. The distinct features of this disease are illustrated. A developmental
      etiology and a new nomenclature for this disease are proposed, along with a
      review of the literature.

PMID- 22606599
TI  - Primary cutaneous melanoma arising in a long-standing irradiated keloid.
AB  - Ionizing radiation has been used therapeutically for a variety of clinical
      conditions, including treatment of hypertrophic keloids. Keloids may rarely be
      associated with malignancy, but the use of low-dose ionizing radiation is
      associated with an increased risk of cutaneous malignancies. We describe a case
      in which a primary desmoplastic melanoma arose in a long-standing, previously
      irradiated keloid.

PMID- 22606600
TI  - Retroperitoneal bronchogenic cyst mimicking hydatid liver: a case report.
AB  - Bronchogenic cysts frequently occur in the mediastinum. They may be rarely
      encountered in the abdomen and retroperitoneum. Bronchogenic cysts can in fact
      mimic hydatid cysts. We report a case of retroperitoneal bronchogenic cyst below
      the right hemidiaphragm mimicking a hydatid cyst of the liver in a 30-year-old
      female.

PMID- 22606601
TI  - Pathologic Complete Response of HER-2 Neu-Positive Invasive Ductal Carcinoma and
      Ductal Carcinoma In Situ following Neoadjuvant Chemotherapy plus Trastuzumab: A
      Case Report and Review of Literature.
AB  - Pathologic complete response (pCR) after NC has been consistently associated with
      improved outcomes. Residual DCIS after NC does not portray worse prognosis
      compared to complete eradication of all disease but has clinical implications
      regarding surgical management. We report a case of pCR of DCIS associated with
      invasive carcinoma in an HER-2 + tumor after NC plus trastuzumab despite
      persistence of malignant-appearing microcalcifications mammographically. A 41
      year-old Caucasian female presented with a 4 * 4 cm mass in the right breast and
      a 2.5 cm right axillary node. Mammogram showed a 2.5 cm mass and a 12 cm area of
      linear pleomorphic, suspicious calcifications in the upper part of the breast.
      Core biopsy revealed invasive ductal carcinoma and DCIS associated with
      calcifications (ER 85%, PR 6%, Her2neu 3+ by IHC). Axillary node FNA was positive
      for malignancy. The patient received doxorubicin/cyclophosphamide (AC) ->
      paclitaxel plus T with complete clinical and radiologic response but no
      significant change in the microcalcifications. Final pathology showed no residual
      invasive carcinoma or DCIS despite the presence of numerous ducts with
      microcalcifications. Documented eradication of DCIS has not been reported
      following NC when malignant-appearing calcifications persist and this observation
      may have important clinical implications regarding surgical management.

PMID- 22606602
TI  - Fitz-hugh-curtis syndrome in a male patient: a case report and literature review.
AB  - Fitz-Hugh-Curtis syndrome is a condition characterized by inflammation of the
      liver capsule with concomitant pelvic inflammation without involvement of liver
      parenchyma. It is classically seen in young women who present with sharp,
      pleuritic right upper quadrant pain, usually but not always accompanied by
      symptoms of pelvic inflammatory disease (PID), and is frequently confused with
      biliary tract disease. Rarely the syndrome has been reported in males, and
      hematogenous and lymphatic spread to liver is thought to be the underlying
      mechanism. Serological tests and computed tomography (CT) scan may aid in
      diagnosis of Fitz-Hugh-Curtis syndrome. Definitive diagnosis is made by
      laparoscopy, which provides both diagnostic and therapeutic benefits. We report a
      case of Fitz-Hugh-Curtis syndrome in a young male patient, which was diagnosed
      and treated by laparoscopy. We also include a review of the literature.

PMID- 22606603
TI  - Posterior mediastinal hematoma after a fall from standing height: a case report.
AB  - Posterior Mediastinal Hematomas (PMHs) secondary to a fall from standing height
      are uncommon, with only one previous case reported in the literature. We describe
      a case of a 78-year-old male with multiple medical comorbidities, who was
      transferred to Montreal General Hospital (MGH) with a posterior mediastinal
      hematoma (PMH) after sustaining a fall from standing height. On initial
      assessment, the patient was hemodynamically stable and complained of mild chest
      pain, dyspnea, fatigue, and diaphoresis. The patient's airway was secured via
      endotracheal intubation fearing impending respiratory compromise secondary to an
      enlarging PMH. The patient was admitted to ICU where over the next 3 days he was
      managed conservatively via careful monitoring of his hemodynamic and hematologic
      indices. Repeat CT scanning indicated reduction in size of the PMH. The patient
      was discharged on hospital day eight. This case describes the assessment,
      evaluation, and conservative management of PMH in a complicated patient receiving
      prior anticoagulation. A review of the literature regarding the epidemiology of
      PMH and the management of both unstable and stable PMHs is also presented.

PMID- 22606604
TI  - An unusual cause of right lower quadrant pain: the caecum diverticulitis.
AB  - Purpose. In the study presented, preoperative examinations and surgical methods
      were discussed along with literature, regarding two cases who were operated with
      the prediagnosis of acute appendicitis and for whom caecum diverticulitis was
      determined. Case 1. 21 years old male patient who had applied to hospital with
      complaint of abdominal pain, underwent an operation with a prediagnosis of acute
      appendicitis. Right hemicolectomy was performed with mass perioperatively
      determined in caecum. Histopathological examination revealed necrosis and
      inflammation in diverticulum wall. Case 2. 36 years old female patient applied to
      emergency department with abdominal pain and underwent an operation with a
      prediagnosis of acute appendicitis. Appendectomy and diverticulectomy were
      performed for whom inflame diverticula in caecum was determined perioperatively.
      Histopathological examination was revealed acute inflammation in diverticulum
      wall. Conclusion. Although solitary caecum diverticulitis is a rarely encountered
      disease, it must be considered in the differential diagnosis of right lower
      abdomen pain.

PMID- 22606605
TI  - Extracorporeal membrane oxygenation for complex multiorgan system trauma.
AB  - With growing experience, the indications for salvage extracorporeal membrane
      oxygenation continue to expand. We describe a successful application of
      extracorporeal support in a polytrauma patient presenting with profound
      hypothermia, respiratory failure, and whom was later found to have an
      intracranial hemorrhage. We advocate the role of salvage therapy even in patients
      with complex pathophysiology despite perceived relative or absolute
      contraindications to extracorporeal support.

PMID- 22606606
TI  - Conservative management of a congenital seminal vesicle cyst associated with
      ipsilateral renal agenesis revealed by cystitis: one case report.
AB  - Seminal vesicle cyst is an extremely rare disease. Its association with
      ipsilateral renal agenesis is even more exceptional. We present herein one case
      of a 16-year-old male who presented with a four-month history of lower urinary
      tract symptoms (LUTSs) and micturition pain. The digital rectal examination
      revealed a small mass arising from the prostate. The urine culture showed that E.
      coli is sensitive to all antibiotics tested. Transrectal ultrasound (TRUS)
      revealed a cystic mass in the outer prostate. Seminal vesicle cyst and left renal
      agenesis were confirmed by magnetic resonance imaging (MRI). Maximum flow
      (Q(max)) at uroflow was greater than 15 mL/sec. We therefore decided to manage
      this disease conservatively with alpha blockers and antibiotics. After 6-month'
      followup the patient did not report any complain and the uroflow test was similar
      to a normal urination. From one case report and literature review, the authors
      suggest a diagnostic and therapeutic strategy for the management of this rare
      condition.

PMID- 22606607
TI  - Primary carcinoid tumor of the ileal efferent limb of an ileovesicostomy: a case
      report.
AB  - We report on the evaluation and management of a 47-year-old white male found to
      have primary carcinoid tumor of the ileal segment of his diverting
      ileovesicostomy thirty-five months after initial creation. Subsequent to
      presentation with intermittent gross hematuria, CT urogram highlights an 8 mm
      enhancing lesion near the enterovesical junction of urinary diversion. Office
      cystoscopy confirms presence of a lesion that was later endoscopically resected
      and found to be a well-differentiated carcinoid tumor. Evaluation with serum
      markers, direct visualization utilizing endoscopy, and imaging was without
      finding of alternate primary or metastatic lesions. The patient ultimately had
      the proximal ileal portion of his ileovesicostomy excised and the distal portion
      converted into an ileal conduit. After briefly discussing the carcinoid tumor and
      the carcinoid syndrome it may cause, we review the literature on the incidence of
      carcinoid tumors in a population requiring the use of intestine in the urinary
      tract.

PMID- 22606608
TI  - Emphysematous cystitis: report of an atypical case.
AB  - We report the atypical case of a nondiabetic 66-year old male with severe
      abdominal pain and vomiting who was found to have emphysematous cystitis. Of all
      gas-forming infections of the urinary tract emphysematous cystitis is the most
      common and the least severe. The major risk factors are diabetes mellitus and
      urinary tract obstruction. Most frequent causative pathogens are Escherichia coli
      and Klebsiella pneumoniae. The clinical presentation is nonspecific and ranges
      from asymptomatic urinary tract infection to urosepsis and septic shock. The
      diagnosis is made by abdominal imaging. Treatment consists of broad-spectrum
      antibiotics, bladder drainage, and management of the risk factors. Surgery is
      reserved for severe cases. Overall mortality rate of emphysematous cystitis is
      7%. Immediate diagnosis and treatment is necessary because of the rapid
      progression to bladder necrosis, emphysematous pyelonephritis, urosepsis, and
      possibly fatal evolution.

PMID- 22606609
TI  - Endovascular treatment of a right-sided ureteroiliac fistula in a patient with a
      simultaneous left-sided ureteroileal fistula.
AB  - We describe an 80-year-old female with a left ureteroileal fistula and
      simultaneously a right ureteroiliac fistula. Her history highlights the
      predisposing factors of radiation, major surgery in the region, and presence of
      bilateral double-J-stents. She was successfully treated with an endovascular
      approach after being initially misdiagnosed. There seems to be an increase in
      reporting ureteral fistulas, however this entity remains a rare clinical
      condition that can lead to life-threatening situations. A fast and accurate
      diagnosis of an ureteroarterial fistula remains a challenge.

PMID- 22606610
TI  - Giant ectopic ureter mimicking pelvic organ prolapse: a case report.
AB  - Ectopic ureter is one of the most common urinary tract anomalies. We, herein,
      present a case of a giant ureter with ectopic orifice, mimicking pelvic organ
      prolapse, which is the first in the literature. A 59-year-old female patient
      presenting with frequently recurrent urinary tract infection had grade 3 pelvic
      organ prolapse. On examination, the organ producing the appearance of prolapse
      was found to be a right ureter of giant size and was obstructed by a large stone
      at the distal segment. The proximal end of the ureter ended blindly. After
      exploration, the stone was removed, the ureter was detached from the urethra, and
      the lumen was tied off and cut 5 cm proximally. At 6 months postoperatively, the
      patient is being followed up without any clinical problems. In such cases with
      nonfunctioning renal segment draining proximally, the chance of cure can be
      obtained without a need for a comprehensive intervention such as total abdominal
      ureterectomy.

PMID- 22606611
TI  - A case report of urinary bladder carcinosarcoma and review of the literature.
AB  - Carcinosarcoma of the bladder is an unusual tumour characterized by a combination
      of malignant epithelial and soft tissue elements. Most of the reported cases have
      been case reports or small series. Optimal treatment is uncertain. We herein
      report our experience in such a case treated with transurethral resection
      followed by radiotherapy with adverse final outcome. Treatment of bladder
      carcinosarcomas should be aggressive and multimodal but optional treatment is
      still unknown. Radiotherapy alone is insufficient as a treatment option of these
      aggressive tumors.

PMID- 22606612
TI  - Generalized lymphadenopathy: unusual presentation of prostate adenocarcinoma.
AB  - Generalized lymphadenopathy is a rare manifestation of metastatic prostate
      cancer. Here, we report the case of a 59-year-old male patient with
      supraclavicular, mediastinal, hilar, and retroperitoneal and inguinal
      lymphadenopathy, which suggested the diagnosis of lymphoma. There were no urinary
      symptoms. A biopsy of the inguinal lymph node was compatible with adenocarcinoma,
      whose prostatic origin was shown by immunohistochemical staining with PSA. The
      origin of the primary tumor was confirmed by directed prostate biopsy. We
      emphasize that a suspicion of prostate cancer in men with adenocarcinoma of
      undetermined origin is important for an adequate diagnostic and therapeutic
      approach.

PMID- 22606613
TI  - Polyarteritis nodosa with bilateral asynchronous testicular necrosis: a case
      report.
AB  - Polyarteritis nodosa (PAN) is a systemic vasculitis which may result in
      thrombosis or aneurysm formation in any organ of the body. We report a case
      polyarteritis nodosa (PAN) resulting in bilateral asynchronous testicular
      necrosis. A 55-year-old male developed acute onset of left testicular pain
      resulting in a left orchiectomy and right orchidopexy for an ischemic left
      testicle without evidence of torsion. Three weeks later, the patient developed
      acute right-sided scrotal pain, and surgical exploration revealed a right
      necrotic testicle resulting in a right orchiectomy. Pathologic evaluations
      demonstrated benign testes with acute interstitial hemorrhage and focal atrophy.
      The patient also experienced abdominal skin necrosis, penile pain and swelling,
      and temporary loss of vision. This is a unique case of PAN and the only case of
      asynchronous testicular necrosis in the medical literature.

PMID- 22606614
TI  - The operative challenges of advanced renal cell carcinoma with vena cava
      involvement: a report of three cases.
AB  - Surgical resection remains an important component in the care of advanced renal
      cell carcinoma (RCC). Some of the patients so managed had relief of symptoms and
      improved quality of life. However, palliative nephrectomies in late cases with
      vena cava involvement are not without challenges. An important factor to be
      considered for successful surgery is adequate vena cava management. We report in
      this paper three patients who had metastatic RCC. For over three decades now,
      researchers in Lagos had recorded the abysmal prognosis of advanced cases of RCC.
      Yet, late presentation and diagnosis still persisted in our environment. There is
      therefore the need to repackage our strategies aimed at early detection of this
      pathology and thus improved postoperative outcome.

PMID- 22606615
TI  - Tumor-to-Tumor Metastasis to Chromophobe Renal Cell Carcinoma: A First Report.
AB  - Tumor-to-tumor metastasis is a rare phenomenon. From our review of the
      international literature, around 150 cases have been reported since it was first
      documented by Campbel in 1868. Renal clear cell carcinoma is well known to be the
      most common recipient of tumor-to-tumor metastasis in all tumors. However, renal
      chromophobe cell carcinoma has not been reported to be a recipient. Here, we
      report a first case of colorectal carcinoma metastatic to chromophobe renal cell
      carcinoma.

PMID- 22606616
TI  - Partial nephrectomy in a patient with a left ventricular assist device.
AB  - Left ventricular assist device (LVAD) use has increased as a bridge to heart
      transplant as well as destination therapy in patients with severe heart failure.
      Presence of LVAD is not a contraindication to noncardiac surgery but does present
      special challenges to the surgical, anesthesia, and cardiac teams. We present the
      case of a 40-year-old woman with idiopathic cardiomyopathy necessitating LVAD who
      underwent left partial nephrectomy for a renal mass. She had undergone three
      nondiagnostic percutaneous image-guided biopsies. Left partial nephrectomy was
      performed. Perioperative care was without incident due to careful oversight by a
      multidisciplinary team. Pathology revealed high-grade clear cell renal cell
      carcinoma (RCC) with negative margins. Polytetrafluoroethylene (PTFE) bolsters
      were misidentified six months postoperatively on computed tomography (CT) at an
      outside institution as a retained laparotomy sponge. This is, to our knowledge,
      the first report of a partial nephrectomy performed in a patient with LVAD.

PMID- 22606617
TI  - Rapid progression of a urinary bladder leiomyosarcoma: report of a case.
AB  - The case we report shows rapid progression and a very poor prognosis only for a
      month that differs from the clinical course reported in the literature. An 83
      year-old man was referred to our hospital for macroscopic hematuria. Computed
      tomography (CT) revealed a large bladder tumor measuring 4 cm * 3 cm and magnetic
      resonance imaging revealed extravesical invasion and pelvic wall invasion of the
      tumors. Chest CT and bone scintigraphy revealed no evidence of distant visceral
      metastases, and a clinical diagnosis of T4N0M0 was made. Transurethral resection
      of the bladder tumor (TUR-BT) was performed for histopathological diagnosis 18
      days after admission, and no further adjuvant treatment was given. At 15 days
      after TUR-BT, the patient's clinical status worsened with symptoms of exertional
      dyspnea. CT showed multiple metastatic lesions in the lung, liver, and
      retroperitoneal lymphadenopathy. The patient died 2 days later and underwent
      autopsy. A final histopathological diagnosis of leiomyosarcoma was made based on
      immunohistochemical staining.

PMID- 22606618
TI  - Partial ureteropelvic junction disruption after blunt trauma: case report.
AB  - Partial ureteropelvic junction disruption as a result of blunt trauma is rare and
      frequently missed by the initial trauma evaluation. Delays in diagnosis have also
      been associated with significant morbidity. A high index of suspicion should lead
      to appropriate investigations, and the management will be determined by the
      severity of the disruption. We present herein a 24-year-old man who was admitted
      to the Emergency Room with multiple organ injuries caused by a severe blunt
      trauma. Emergency celiotomy was performed for massive hemoperitoneum and
      shattered spleen which led to splenectomy. The diagnosis of partial UPJ
      disruption was missed preoperatively and suspected in CT scan after appearance of
      flank tender mass. Confirmation was obtained in retrograde ureteropyelography and
      treated conservatively with indwelling ureteral stent. We present herein an
      extensive review of the literature to examine the current status of this entity
      and to determine if improvements could be made in the diagnosis and treatment.

PMID- 22606619
TI  - Upper pole nephrectomy: a simplified technique using a retroperitoneal
      laparoscopic approach.
AB  - Objective. To describe a simplified technique already used in our institution for
      several years in the open heminephrectomy for duplication anomalies, now
      performed through a retroperitoneal laparoscopic approach. Methods. The technique
      begins with upper pole parenchyma incision since the demarcation between the
      affected upper moiety and the healthy lower pole is easily established. The
      dissection proceeds until the urothelium of the collecting system is entered,
      which will guide further excision, minimizing damage of the surrounding
      structures. The vascular supply is then identified since the upper pole is
      attached to the remaining renal parenchyma only by these structures that can be
      safely divided. Dissection and division of the ectopic ureter is carried next.
      Results. The operative time was 188 minutes. The blood loss was not significant,
      and there were no other complications during the procedure. The patient was
      discharged home 48 hours after the procedure, without any early or late
      postoperative complications. Conclusion. We believe this simplified technique
      allows a safer excision of nonfunctioning upper pole renal tissue by avoiding the
      initial dissection of the renal hilum, which associated with the known advantages
      of a laparoscopic approach makes us consider it the procedure of choice for upper
      pole nephrectomy in children.

PMID- 22606620
TI  - Liposarcoma of the spermatic cord: a rare entity.
AB  - Primary malignant tumours of spermatic cord are rare. The liposarcoma of
      spermatic cord is a rare entity and only a few cases have been reported in the
      literature. We report a case of forty five-year-old male with huge left
      inguinoscrotal swelling. Fine needle aspiration cytology (FNAC) of swelling
      revealed the diagnosis of a liposarcoma. The patient was subjected to radical
      orchidectomy and wide excision. Histopathological examination (HPE) of the
      resected specimen reported a well-differentiated liposarcoma of the spermatic
      cord and confirmed the diagnosis.

PMID- 22606621
TI  - Bell clapper testis, torsion, and detorsion: a case report.
AB  - We are presenting a common but interesting case of testicular torsion. Torsion is
      a common important urological emergency. History and examination is important for
      diagnosis. Urgent testicular exploration is an important message if in doubt.

PMID- 22606622
TI  - Sarcomatoid carcinoma of the prostate: ductal adenocarcinoma and stromal sarcoma
      like appearance: a rare association.
AB  - Sarcomatoid carcinoma (SC) of prostate gland is a rare biphasic tumour. In about
      half of cases, initial diagnosis is acinar adenocarcinoma, followed by
      nonsurgical therapy, with a subsequent diagnosis of SC. The survival rate is
      lower. We report a case of an 59-years-old man with unusual histopathologic
      finding of prostate sarcomatoid carcinoma, showing characteristics of ductal
      prostatic adenocarcinoma and prostatic stromal sarcoma-like appearance. Ductal
      adenocarcinoma was characterized by tall columnar cells with abundant amphophilic
      to eosinophil cytoplasm. Pleomorphic sarcoma was characterized to have overall
      glandular growth pattern, simulating a malignant phyllodes tumour. Estrogen and
      progesterone receptors showed nuclear immunostaining in mesenchymal
      multinucleated giant cells. In conclusion, SC of the prostate is an exceedingly
      rare tumour. Retrospective analyses render prostate SC as one of the most
      aggressive prostate malignancies. The prognosis is dismal regardless of other
      histologic or clinical findings.

PMID- 22606623
TI  - A case of laparoscopic excision of a huge retroperitoneal cystic lymphangioma.
AB  - Retroperitoneal cystic lymphangioma is a rare benign tumor. Most patients
      eventually experience some symptoms that necessitate therapeutic intervention.
      Excision is the treatment of choice, and some cases of laparoscopic resection
      have been reported. We report another case of a huge retroperitoneal cystic
      lymphangioma that was successfully excised laparoscopically with the SAND balloon
      catheter. Large cystic lymphangioma was downsized by puncturing and aspirated
      with the SAND balloon catheter. Laparoscopic surgical technique should be
      considered for treatment of selected cystic lesions of retroperitoneal origin.

PMID- 22606624
TI  - Congenital anterior urethral diverticulum in a male teenager: a case report and
      review of the literature.
AB  - We present the case of a 13-year-old boy with a congenital anterior urethral
      diverticulum. This is a rare condition in males which can lead to obstructive
      lower urinary tract symptoms and urosepsis. Diagnosis is by urethroscopy and
      radiological imaging. Surgical treatment can be open or endoscopic. Long-term
      followup is required to check for reoccurrence of the obstruction.

PMID- 22606625
TI  - Primary renal synovial sarcoma.
AB  - Synovial sarcomas are generally deep-seated tumors that most often occur in the
      proximity of large joints of adolescents and young adults. We describe two cases
      of primary renal synovial sarcoma that were treated successfully by radical
      nephrectomy. Synovial sarcoma originating from the kidney is extremely rare and
      the histogenesis is uncertain. Surgical resection and ifosfamide based
      chemotherapy are the mainstay for the management of renal synovial sarcoma. Fewer
      than 40 patients have been described in the English literature. Physicians should
      be aware of the possibility of malignancy in cystic renal masses and raise the
      suspicion of synovial sarcoma, especially when patients with renal masses are a
      young adult.

PMID- 22606626
TI  - Synchronous renal malignancy presenting as recurrent urinary tract infections.
AB  - Renal cell carcinoma (RCC) and urothelial carcinoma of the upper urinary tract
      are not uncommon urological malignancies. Their simultaneous occurrence in a
      patient is, however, extraordinarily rare. We report the case of a patient who
      underwent unilateral nephrectomy for suspected RCC and diagnosed transitional
      cell carcinoma of the superior pelvis. Preoperative imaging was suspicious for
      renal pelvic involvement, which was confirmed upon performing cystoscopy and
      biopsy of the suspected lesion preoperatively. This preoperative approach was
      especially appropriate as a nephron saving procedure was being considered prior
      to the discovery of the synchronous lesion. We discuss this rare simultaneous
      occurrence of synchronous malignancies in the same kidney.

PMID- 22606627
TI  - Papillary adenocarcinoma of rete testis mimics inflammatory lump: a case report.
AB  - We presented a rare extratesticular neoplasm, papillary adenocarcinoma of rete
      testis, which manifested variable symptoms and mimicked most frequently seen
      benign extratesticular lesions. Due to its rarity, the treatment is therefore
      uncertain. Our patient's clinical manifestations mimicked an inflammatory lump
      and underwent radical orchiectomy after pathological report had been confirmed.
      Unlike other reports, our patient survives and has a good outcome. No definite
      predictor and tumor marker can be used to define the prognosis. Early diagnosis
      and surgical treatment may have a good outcome.

PMID- 22606628
TI  - Spectacularly successful microsurgical penile replantation in an assaulted
      patient: one case report.
AB  - Penile amputation is a rare condition for which immediate surgical replantation
      is warranted. We present herein one case of a 27-year-old male who presented to
      the Emergency Department after his wife cut his penis. The penis was replanted
      microsurgically. The deep dorsal penile veins and superficial veins were
      anastomosed. Although we could not reanastomose the arteries, wound healing
      occurred without any problem one week postoperatively and the patient regained
      erectile function 4 weeks after surgery. At 1-year follow-up examinations he
      reported on restored erectile function and a normal urinary function.

PMID- 22606629
TI  - Primary malignant melanoma of the urinary bladder.
AB  - Introduction. Primary melanoma of the urinary bladder is very rare. As far as we
      know, 19 cases have been reported worldwide, usually as case reports. Case
      Presentation. We present a 71-year-old male patient presented with a 2-month
      history of hematuria. Ultrasonography revealed a 5-cm-size mass located in the
      bladder trigone. A transurethral resection of the bladder tumor (TURBT) revealed
      a malignant melanoma. Evaluation for metastatic disease was negative. The patient
      deceased five months later before radical treatment could be performed.
      Conclusion. This is one more reported case of primary melanoma of the urinary
      bladder. The previously reported cases of bladder melanoma are reviewed. Therapy
      and prognosis are discussed.

PMID- 22606630
TI  - Posterior urethra rupture: contrast-enhanced computed tomography scan and
      urethrocystography demonstrations.
AB  - In the follow-up study of patients with pelvic fractures, rupture of the
      posterior urethra is registered in 3-25% of cases (Koraitim et al., 1996). The
      diagnostic gold standard for the assessment of hemodynamically stable trauma
      patients is contrast-enhanced CT scan, especially helical CT. Nevertheless,
      simultaneous suprapubic cystography and ascending urethrograms (the so-called up
      and-downogram) are the investigation of choice in assessing the site, severity,
      and length of urethral injuries. (Carlin and Resnick, 1995) This paper discusses
      the evaluation and diagnosis of urethral injury in multiple-trauma patient.

PMID- 22606631
TI  - Epididymal leiomyosarcoma: one case report.
AB  - Epididymal leiomyosarcoma is very uncommon. Only 16 cases have been reported in
      the literature. There has never been a reported case of a patient with an African
      origin with this tumor. We report the medical history of a 70-year-old man who
      presented an enormous mass located in his epididymis. A tricut biopsy was
      performed which allowed histological confirmation of epididymal leiomyosarcoma
      after which the patient underwent excision of the mass. The patient died after
      the first round of chemotherapy.

PMID- 22606632
TI  - Renal pelviceal keratinizing squamous metaplasia with sparing of pyramidal zones.
AB  - Metaplastic changes in the urothelium of the upper urinary tract are relatively
      infrequent. Metaplasia may present as either squamous or less often glandular
      differentiation. The process may be associated with chronic inflammation or
      associated chronic infections. There may be malignant transformation to either
      squamous cell carcinoma or adenocarcinoma. The demarcation of the metaplastic
      process in the minor calyces has not been well documented to date. We report the
      case of a 74-year-old female patient who presented with a history of chronic
      renal disease and acute pyohydronephrosis. The patient underwent a
      nephroureterectomy which revealed keratinizing desquamative squamous metaplasia
      throughout the renal pelvis and upper urinary tract with abrupt termination of
      metaplasia at the junction of the renal pelvis and the minor calyx (pyramidal
      zone). Immunohistochemical evaluation documents metaplastic urothelium stained
      positive for CK5, before converting sharply to simple cuboidal epithelium in the
      minor calyx (pyramidal zones) which stained positive CK7. At the junction of the
      metaplastic components and low cuboidal lined minor calyceal surfaces, the
      underlying stroma showed loss of ureteral muscularis mucosa with transition to
      renal parenchymal type stroma. We believe that this observation is unique and
      potentially relevant to the etiology and pathophysiology of pelviceal metaplasia.

PMID- 22606633
TI  - Renal metastases of a femur osteosarcoma: a case report and a review of the
      literature.
AB  - This paper discusses a rare case of renal metastatic osteosarcoma. A 25-year-old
      man with a history of metastatic osteosarcoma involving his right kidney was
      referred to our institution for treatment. He was managed with chemotherapy. An
      exhaustive review of the English literature pertaining to this disease was
      performed. To our knowledge, this case represents only the sixteenth. The
      literature suggests that the incidence of renal involvement in osteosarcoma is
      significant and that the treatment should be multidisciplinary in such patients.

PMID- 22606634
TI  - Actinobaculum schaalii: An Emerging Uropathogen?
AB  - A. schaalii is a rare uropathogen. We report urosepsis with Actinobaculum
      schaalii detected serendipitously in blood and urine culture in a 79-year-old
      with urinary tract obstruction. This paper illuminates the flaws in our current
      system in detecting A. schaalii and raises awareness among clinicians and
      laboratory teams.

PMID- 22606636
TI  - Percutaneous holmium laser fulguration of calyceal diverticula.
AB  - Introduction. Calyceal diverticular stones are uncommon findings that represent a
      challenge in their treatment, due to the technical difficulty in accessing the
      diverticulum, and the high risk of their recurrence. Current percutaneous
      technique for calyceal diverticular stones involves establishing a renal access,
      clearing the stone, and fulguration of the diverticular lining with a roller-ball
      cautery electrode using hypotonic irrigation solution such as sterile water or
      glycine solution which may be associated with the absorption of hypotonic fluids
      with its inherent electrolyte disturbances. Case Report. In this paper, we
      present for the first time percutaneous holmium laser fulguration of calyceal
      diverticula in 2 patients using normal saline. Their immediate postoperative
      sodium was unchanged and their follow-up imaging showed absence of stones. Both
      patients remain asymptomatic at 30 months post-operatively. Conclusion. This
      demonstrates that holmium laser is a safe alternative method to fulgurate the
      calyceal diverticulum after clearing the stone percutaneously.

PMID- 22606635
TI  - Leydig Cell Tumor Associated with Testicular Adrenal Rest Tumors in a Patient
      with Congenital Adrenal Hyperplasia due to 11beta-Hydroxylase Deficiency.
AB  - Congenital adrenal hyperplasia (CAH) describes a group of inherited autosomal
      recessive disorders characterized by enzyme defects in the steroidogenic pathways
      that lead to the biosynthesis of cortisol, aldosterone, and androgens. Chronic
      excessive adrenocorticotropic hormone (ACTH) stimulation may result in
      hyperplasia of ACTH-sensitive tissues in adrenal glands and other sites such as
      the testes, causing testicular masses known as testicular adrenal rest tumors
      (TARTs). Leydig cell tumors (LCTs) are make up a very small number of all
      testicular tumors and can be difficult to distinguish from TARTs. This
      distinction is interesting because LCTs and TARTs require different therapeutic
      approaches. Hereby, we present an unusual case of a 19-year-old patient with CAH
      due to 11beta-hydroxylase deficiency, who presented with TARTs and an epididymal
      Leydig cell tumor.

PMID- 22606637
TI  - Giant Urinary Bladder and Bilateral Giant Hydronephrosis due to Bladder Neck
      Obstruction: One Case Report and Literature Review.
AB  - Bilateral hydronephrosis secondary to urinary obstruction leads to a buildup of
      back pressure in the urinary tract and may lead to impairment of renal function.
      Cases of giant hydronephrosis are rare and usually contain no more than 1-2
      litres of fluid in the collecting system. Here, we report a rarely seen case with
      giant urinary bladder and bilateral giant hydronephrosis due to bladder neck
      obstruction which contains 4000 mL fluid in the collecting system of the kidney
      mimicking an ascites in an adult male.

PMID- 22606638
TI  - Case Report: Successful Staged Ureteroscopic Treatment of a 5 cm Staghorn Renal
      Calculus.
AB  - It is widely accepted that percutaneous nephrostolithotorny (PCNL) is the
      standard of choice for the removal of large staghorn renal calculi. Although data
      exists supporting a stagad ureteroscopic as an alternate treatment for stones up
      to 3 cm in select patients, little data exists to support a ureteroscopic
      approach for stones as large as 5 cm. We present a case of a 68 year old female
      with a 5 cm staghorn renal calculus managed successfully with a staged
      ureteroscopic approach. A staged ureteroscopic approach can be effective in
      treating stones as large as 5 cm.

PMID- 22606639
TI  - CEUS Retrograde Cystography Is Helpful in Percutaneous Drainage of Complex
      Posttransplant Lymphocele.
AB  - After monolateral dual kidney transplantation, a 69 years old male patient
      developed symptomatic lymphocele with mild hydroureteronephrosis, impaired renal
      function, and right inferior limb oedema. A percutaneous ultrasound-guided
      drainage of the fluid collection was planned, but the complex mutual relations
      between the collection and the renal hilus did not allow to identify a suitable
      route for a safe drainage insertion during conventional ultrasound examination. A
      retrograde cystography using echographic contrast agent was, therefore,
      performed, and it clarified the position of both ureters and the renal vessels,
      permitting an harmless ultrasound-guided percutaneous lymphocele drainage. In
      conclusion contrast-enhanced ultrasound retrograde cystography may be helpful in
      percutaneous drainage of complex posttransplant lymphocele.

PMID- 22606640
TI  - Protective effect of melatonin on acute pancreatitis.
AB  - Melatonin, a product of the pineal gland, is released from the gut mucosa in
      response to food ingestion. Specific receptors for melatonin have been detected
      in many gastrointestinal tissues including the pancreas. Melatonin as well as its
      precursor, L-tryptophan, attenuates the severity of acute pancreatitis and
      protects the pancreatic tissue from the damage caused by acute inflammation. The
      beneficial effect of melatonin on acute pancreatitis, which has been reported in
      many experimental studies and supported by clinical observations, is related to:
      (1) enhancement of antioxidant defense of the pancreatic tissue, through direct
      scavenging of toxic radical oxygen (ROS) and nitrogen (RNS) species, (2)
      preservation of the activity of antioxidant enzymes; such as superoxide dismutase
      (SOD), catalase (CAT), or glutathione peroxidase (GPx), (3) the decline of pro
      inflammatory cytokine tumor necrosis alpha (TNFalpha) production, accompanied by
      stimulation of an anti-inflammatory IL-10, (4) improvement of pancreatic blood
      flow and decrease of neutrophil infiltration, (5) reduction of apoptosis and
      necrosis in the inflamed pancreatic tissue, (6) increased production of chaperon
      protein (HSP60), and (7) promotion of regenerative process in the pancreas.
      Conclusion. Endogenous melatonin produced from L-tryptophan could be one of the
      native mechanisms protecting the pancreas from acute damage and accelerating
      regeneration of this gland. The beneficial effects of melatonin shown in
      experimental studies suggest that melatonin ought to be employed in the clinical
      trials as a supportive therapy in acute pancreatitis and could be used in people
      at high risk for acute pancreatitis to prevent the development of pancreatic
      inflammation.

PMID- 22606641
TI  - Identification of Medicinally Active Ingredient in Ultradiluted Digitalis
      purpurea: Fluorescence Spectroscopic and Cyclic-Voltammetric Study.
AB  - Serially diluted and agitated (SAD) drugs available commercially are in use with
      great faith because of the astonishing results they produce. The scientific
      viewpoint attached to the centuries-old therapy with SAD drugs, as in homeopathy,
      remained doubtful for want of appropriate research and insufficient evidence
      base. The conflicting points related to SAD drug mostly related to the level of
      concentrations/dilutions, use of drug in contradictory clinical conditions
      compared to the modern system of medicine, identification of medicinally active
      ingredient in concentrations and dilutions used in commercially available SAD
      drugs, and lack of laboratory-based pharmacological data vis-a-vis modern
      medicine. Modus operandi of SAD drug is also unknown. To address some of these
      issues an analytical study was carried out wherein commercially available SAD
      drug Digitalis purpurea, commonly used in different systems of medicine, was put
      to test. Various concentrations of commercially available Digitalis purpurea were
      analyzed using analytical methods: cyclic voltammetry, emission spectroscopy, and
      UV-VIS spectroscopy. These analytical methods apparently identified the medicinal
      ingredients and effect of serial dilution in commercial preparation of the drugs.

PMID- 22606642
TI  - Comparison of a fistulectomy and a fistulotomy with marsupialization in the
      management of a simple anal fistula: a randomized, controlled pilot trial.

PMID- 22606643
TI  - Is abdominal computed tomography helpful for the management of an intestinal
      obstruction caused by a bezoar?

PMID- 22606644
TI  - Factors Influencing Oncologic Outcomes after Tumor-specific Mesorectal Excision
      for Rectal Cancer.

PMID- 22606645
TI  - Aluminum potassium sulfate and tannic Acid injection for hemorrhoids.
AB  - A quick hemostatic effect, as well as sclerosing and shrinkage of hemorrhoids,
      can be attained when internal hemorrhoids are treated by using injection therapy
      with aluminum potassium sulfate and tannic acid (ALTA), the outcomes of treatment
      may be similar to those of a hemorrhoidectomy. However, if the type of hemorrhoid
      or the method of injection is not appropriate for ALTA treatment, complications
      peculiar to ALTA or recurrence may develop. Accordingly, sufficient understanding
      of the treatment mechanism of ALTA injection and repeated training for injection
      are required for effective use of the ALTA treatment.

PMID- 22606646
TI  - Comparison of a fistulectomy and a fistulotomy with marsupialization in the
      management of a simple anal fistula: a randomized, controlled pilot trial.
AB  - PURPOSE: This randomized clinical trial was conducted to compare a fistulectomy
      and a fistulotomy with marsupialization in the management of a simple anal
      fistula. METHODS: Forty patients with simple anal fistula were randomized into
      two groups. Fistulous tracts were managed by using a fistulectomy (group A) while
      a fistulotomy with marsupialization was performed in group B. The primary outcome
      measure was wound healing time while secondary outcome measures were operating
      time, postoperative wound size, postoperative pain, wound infection, anal
      incontinence, recurrence and patient satisfaction. RESULTS: Postoperative wounds
      in group B healed earlier in comparison to group A wounds (4.85 +/- 1.39 weeks
      vs. 6.75 +/- 1.83 weeks, P = 0.035). No significant differences existed between
      the operating times (28.00 +/- 6.35 minutes vs. 28.20 +/- 6.57 minutes, P =
      0.925) and visual analogue scale scores for postoperative pain on the first
      postoperative day (4.05 +/- 1.47 vs. 4.50 +/- 1.32, P = 0.221) for the two
      groups. Postoperative wounds were larger in group A than in group B (2.07 +/-
      0.1.90 cm(2) vs. 1.23 +/- 0.87 cm(2)), however this difference did not reach
      statistical significance (P = 0.192). Wound discharge was observed for a
      significantly longer duration in group A than in group B (4.10 +/- 1.91 weeks vs.
      2.75 +/- 1.71 weeks, P = 0.035). There were no differences in social and sexual
      activities after surgery between the patients of the two groups. No patient
      developed anal incontinence or recurrence during the follow-up period of twelve
      weeks. CONCLUSION: In comparison to a fistulectomy, a fistulotomy with
      marsupialization results in faster healing and a shorter duration of wound
      discharge without increasing the operating time.

PMID- 22606647
TI  - Intestinal Anastomosis by Use of a Memory-shaped Compression Anastomosis Clip
      (Hand CAC 30): Early Clinical Experience.
AB  - PURPOSE: The safety and the efficacy of the compression anastomosis clip (Hand
      CAC 30) have been demonstrated by animal studies. This study was designed to
      evaluate the clinical validity of the Hand CAC 30 in enterocolic side-to-side
      anastomosis after colonic or enteric resections. METHODS: A non-randomized
      prospective data collection was performed for patients undergoing a side-to-side
      anastomosis using the Hand CAC 30. Eligibility criteria for the use of the Hand
      CAC 30 were for anastomoses between the colon and the ileum or between two small
      bowels. The primary short-term endpoint was the rate of anastomotic leakage.
      Other clinical outcomes, including intra- and postoperative complications, length
      of operation time and hospital stay, and the clip elimination time were recorded.
      RESULTS: A total of 63 patients (male, 36) underwent an enteric or right-sided
      colonic resection followed by a side-to-side anastomosis using the Hand CAC 30.
      Laparoscopic surgery was performed in 36 patients, in whom one patient who
      underwent a laparoscopic right hemicolectomy was converted to an open procedure
      (1/32, 3.1%). One patient with ascending colon cancer showed postoperative
      anastomotic leakage and died of co-morbid ischemic heart disease. There were no
      other surgical mortalities. The exact date of expulsion of the clip could not be
      recorded because most patients were not aware of clip elimination. No patients
      manifested clinical symptoms of anastomotic stricture. CONCLUSION: Short-term
      evaluation of the Hand CAC 30 anastomosis in patients undergoing enterocolic
      surgery proved it to be a safe and efficacious alternative to the standard hand
      sewn or stapling technique.

PMID- 22606648
TI  - Bezoar-induced Small Bowel Obstruction.
AB  - PURPOSE: The aim of this study was to observe the clinical features of a bezoar
      induced small bowel obstruction and to investigate the role of abdominal computed
      tomography (CT) in establishing the diagnosis. METHODS: We retrospectively
      reviewed 20 cases of bezoar-induced small bowel obstruction in our hospital from
      1996 to 2010. RESULTS: Thirteen patients (65%) had a history of abdominal
      surgery. Nine patients (45%) were diagnosed with a bezoar before surgery, seven
      patients were diagnosed by using abdominal CT, and two patients were diagnosed
      with a small bowel series. Abdominal CT was performed in 15 patients, and the
      diagnostic accuracy was 47% (7/15). Surgery revealed ten bezoars in the jejunum
      and 11 in the ileum. Two patients had bezoars found concurrently in the stomach.
      Spontaneous removal took place in two patients. An enterotomy and bezoar
      extraction was performed in 15 patients. Fragmentation and milking, a small bowel
      resection, and a Meckel's diverticulectomy were performed in one patient each.
      Early operative treatment was possible (P = 0.036) once the bezoar had been
      diagnosed by using abdominal CT. There tended to be fewer postoperative
      complications in patients who were diagnosed with a bezoar by using abdominal CT,
      but the result was not statistically significant (P = 0.712). CONCLUSION: A
      preoperative diagnosis of bezoar-induced small bowel obstruction by using
      clinical features was difficult. Increased use of abdominal CT led to a more
      accurate diagnosis and to earlier surgery for bezoar-induced small bowel
      obstructions, thereby reducing the rate of complications.

PMID- 22606649
TI  - Clinical Characteristics and Surgical Safety in Patients with Acute Appendicitis
      Aged over 80.
AB  - PURPOSE: The aim of this study was to evaluate the clinical characteristics and
      treatment outcomes, including surgical safety, in patients over 80 years of age
      who underwent an appendectomy. METHODS: This study involved 160 elderly patients
      who underwent an appendectomy for acute appendicitis: 28 patients over 80 years
      old and 132 patients between 65 and 79 years old. RESULTS: The rate of positive
      rebound tenderness was significantly higher in the over 80 group (P = 0.002).
      Comparisons of comorbidity, diagnostic tool and delay in surgical treatment
      between the two groups were not statistically different. American Society of
      Anesthesiologists score was significantly higher in the over 80 group than in the
      65 to 79 group (2.4 +/- 0.5 vs. 1.6 +/- 0.5; P < 0.00005). Comparisons of
      operative times and use of drainage between the two groups were not statistically
      different. In the pathologic findings, periappendiceal abscess was more frequent
      in the over 80 group (P = 0.011). No significant differences existed between the
      two groups when comparing the results of gas out and the time to liquid diet, but
      the postoperative hospital stay was significantly longer in the over 80 group (P
      = 0.001). Among the postoperative complications, pulmonary complication was
      significantly higher in the over 80 group (P = 0.005). However, operative
      mortality was zero in each group. CONCLUSION: In case of suspicious appendicitis
      in elderly patients, efforts should be made to use aggressive diagnostic
      intervention, do appropriate surgery and prevent pulmonary complications
      especially in patients over 80 years of age.

PMID- 22606650
TI  - Oncologic Outcomes and Risk Factors for Recurrence after Tumor-specific
      Mesorectal Excision of Rectal Cancer: 782 Cases.
AB  - PURPOSE: The aim of this study was to analyze the oncologic outcomes and the risk
      factors for recurrence after a tumor-specific mesorectal excision (TSME) of
      resectable rectal cancer in a single institution. METHODS: A total of 782
      patients who underwent a TSME for resectable rectal cancer between February 1995
      and December 2005 were enrolled retrospectively. Oncologic outcomes included 5
      year cancer-specific survival and its affecting factors, as well as risk factors
      for local and systemic recurrence. RESULTS: The 5-year cancer-specific survival
      rate was 77.53% with a mean follow-up period of 61 +/- 31 months. The overall
      local and systemic recurrence rates were 9.2% and 21.1%, respectively. The risk
      factors for local recurrence were pN stage (P = 0.015), positive distal resection
      margin, and positive circumferential resection margin (P < 0.001). The risk
      factors for systemic recurrence were pN stage (P < 0.001) and preoperative
      carcinoembryonic antigen level (P = 0.005). The prognostic factors for cancer
      specific survival were pT stage (P < 0.001), pN stage (P < 0.001), positive
      distal resection margin (P = 0.005), and positive circumferential resection
      margin (P = 0.016). CONCLUSION: The oncologic outcomes in our institution after a
      TSME for patients with resectable rectal cancer were similar to those reported in
      other recent studies, and we established the risk factors that could be crucial
      for the planning of treatment and follow-up.

PMID- 22606651
TI  - Giant peritoneal loose body in the pelvic cavity.
AB  - We report a case of a large peritoneal loose body diagnosed on computed
      tomography. The most common causes of a peritoneal loose body are thought to be
      torsion and separation of the appendices epiploicae. Peritoneal loose bodies are
      usually small, 0.5 to 2.5 cm in diameter. However, "giant" peritoneal loose
      bodies, larger than 4 cm in diameter, are an uncommon disease and present with
      various symptoms, and are difficult to diagnose preoperatively. Especially,
      abdominal large peritoneal loose bodies are frequently misdiagnosed as tumorous
      disease preoperatively. In our case, the loose body appeared as a round pelvic
      mass with central calcifications and a distinct fat plane separating it from
      adjacent organs. Preoperatively, we suspected a tumorous lesion from the wall of
      the upper rectum; however, at laparoscopy, a large peritoneal loose body was
      detected. An extraction of the giant peritoneal loose body was performed
      laparoscopically.

PMID- 22606652
TI  - A case of primary ovarian lymphoma presenting as a rectal submucosal tumor.
AB  - Primary ovarian lymphoma is a rare malignancy whose symptoms or signs are usually
      nonspecific. In this article, we report a very rare case initially presenting as
      a rectal submucosal-tumor-like lesion with a defecation disturbance caused by
      primary ovarian lymphoma with bilateral involvement. A 42-year-old woman visited
      chungnam national university hospital complaining of persistent defecation
      disturbance for 6 months. Colonoscopy demonstrated compression of the rectum by
      an extrinsic mass mimicking a rectal submucosal tumor. Magnetic resonance imaging
      detected bilateral ovarian tumors, 9.3 cm and 5.4 cm each in diameter,
      compressing the rectum without enlarged lymph nodes. The diagnosis was
      established following a bilateral adnexectomy and histological studies of the
      excised tissue. The tumor was classified as a diffuse large B-cell lymphoma. The
      patient was prescribed six cycles of standard CHOP (cyclophosphamide,
      hydroxydaunorubicin, vincristine, prednisolone) regimen and is presently on
      treatment.

PMID- 22606653
TI  - Volumetric Medical Image Coding: An Object-based, Lossy-to-lossless and Fully
      Scalable Approach.
AB  - In this article, an object-based, highly scalable, lossy-to-lossless 3D wavelet
      coding approach for volumetric medical image data (e.g., magnetic resonance (MR)
      and computed tomography (CT)) is proposed. The new method, called 3DOBHS-SPIHT,
      is based on the well-known set partitioning in the hierarchical trees (SPIHT)
      algorithm and supports both quality and resolution scalability. The 3D input data
      is grouped into groups of slices (GOS) and each GOS is encoded and decoded as a
      separate unit. The symmetric tree definition of the original 3DSPIHT is improved
      by introducing a new asymmetric tree structure. While preserving the compression
      efficiency, the new tree structure allows for a small size of each GOS, which not
      only reduces memory consumption during the encoding and decoding processes, but
      also facilitates more efficient random access to certain segments of slices. To
      achieve more compression efficiency, the algorithm only encodes the main object
      of interest in each 3D data set, which can have any arbitrary shape, and ignores
      the unnecessary background. The experimental results on some MR data sets show
      the good performance of the 3DOBHS-SPIHT algorithm for multi-resolution lossy-to
      lossless coding. The compression efficiency, full scalability, and object-based
      features of the proposed approach, beside its lossy-to-lossless coding support,
      make it a very attractive candidate for volumetric medical image information
      archiving and transmission applications.

PMID- 22606654
TI  - CBMIR: Content-based Image Retrieval Algorithm for Medical Image Databases.
AB  - We propose a novel algorithm for the retrieval of images from medical image
      databases by content. The aim of this article is to present a content-based
      retrieval algorithm that is robust to scaling, with translation of objects within
      an image. For the best result and efficient representation and retrieval of
      medical images, attention is focused on the methodology, and the content of
      medical images is represented by the regions and relationships between such
      objects or regions of the Image Attributes (IA) of the objects. The CBMIR employs
      a new model in which each image is first decomposed into regions. The similarity
      measurement between images is developed based on a scheme that integrates the
      properties of all the regions in the images using regional matching. The method
      can answer queries by example. The efficiency and performance of the presented
      method has been evaluated using a dataset of about 5,000 simulated, but realistic
      computed tomography and magnetic resonance images, from which the original images
      are selected from three large medical image databases. The results of our
      experiments show more than a 93 percent success rate, which is satisfactory.

PMID- 22606655
TI  - A Cellular Automata-based Model for Simulating Restitution Property in a Single
      Heart Cell.
AB  - Ventricular fibrillation is the cause of the most sudden mortalities. Restitution
      is one of the specific properties of ventricular cell. The recent findings have
      clearly proved the correlation between the slope of restitution curve with
      ventricular fibrillation. This; therefore, mandates the modeling of cellular
      restitution to gain high importance. A cellular automaton is a powerful tool for
      simulating complex phenomena in a simple language. A cellular automaton is a
      lattice of cells where the behavior of each cell is determined by the behavior of
      its neighboring cells as well as the automata rule. In this paper, a simple model
      is depicted for the simulation of the property of restitution in a single cardiac
      cell using cellular automata. At first, two state variables; action potential and
      recovery are introduced in the automata model. In second, automata rule is
      determined and then recovery variable is defined in such a way so that the
      restitution is developed. In order to evaluate the proposed model, the generated
      restitution curve in our study is compared with the restitution curves from the
      experimental findings of valid sources. Our findings indicate that the presented
      model is not only capable of simulating restitution in cardiac cell, but also
      possesses the capability of regulating the restitution curve.

PMID- 22606656
TI  - A novel method for trajectory planning of cooperative mobile manipulators.
AB  - We have designed a two-stage scheme to consider the trajectory planning problem
      of two mobile manipulators for cooperative transportation of a rigid body in the
      presence of static obstacles. In the first stage, with regard to the static
      obstacles, we develop a method that searches the workspace for the shortest
      possible path between the start and goal configurations, by constructing a graph
      on a portion of the configuration space that satisfies the collision and closure
      constraints. The final stage is to calculate a sequence of time-optimal
      trajectories to go between the consecutive points of the path, with regard to the
      nonholonomic constraints and the maximum allowed joint accelerations. This
      approach allows geometric constraints such as joint limits and closed-chain
      constraints, along with differential constraints such as nonholonomic velocity
      constraints and acceleration limits, to be incorporated into the planning scheme.
      The simulation results illustrate the effectiveness of the proposed method.

PMID- 22606657
TI  - Fuzzy logic controller for hemodialysis machine based on human body model.
AB  - Fuzzy controllers are being used in various control schemes. The aim of this
      study is to adjust the hemodialysis machine parameters by utilizing a fuzzy logic
      controller (FLC) so that patient's hemodynamic condition remains stable during
      hemodialysis treatment. For this purpose, a comprehensive mathematical model of
      the arterial pressure response during hemodialysis, including hemodynamic,
      osmotic, and regulatory phenomena has been used. The multi-input multi-output
      (MIMO) fuzzy logic controller receives three parameters from the model (heart
      rate, arterial blood pressure, and relative blood volume) as input. According to
      the changes in the controller input values and its rule base, the outputs change
      so that the patient's hemodynamic condition remains stable. The results of the
      simulations illustrate that applying the controller can improve the stability of
      a patient's hemodynamic condition during hemodialysis treatment and it also
      decreases the treatment time. Furthermore, by using fuzzy logic, there is no need
      to have prior knowledge about the system under control and the FLC is compatible
      with different patients.

PMID- 22606658
TI  - A review of coronary vessel segmentation algorithms.
AB  - Coronary heart disease has been one of the main threats to human health. Coronary
      angiography is taken as the gold standard; for the assessment of coronary artery
      disease. However, sometimes, the images are difficult to visually interpret
      because of the crossing and overlapping of vessels in the angiogram. Vessel
      extraction from X-ray angiograms has been a challenging problem for several
      years. There are several problems in the extraction of vessels, including: weak
      contrast between the coronary arteries and the background, unknown and easily
      deformable shape of the vessel tree, and strong overlapping shadows of the bones.
      In this article we investigate the coronary vessel extraction and enhancement
      techniques, and present capabilities of the most important algorithms concerning
      coronary vessel segmentation.

PMID- 22606659
TI  - An overview of randomization and minimization programs for randomized clinical
      trials.
AB  - Randomization is an essential component of sound clinical trials, which prevents
      selection biases and helps in blinding the allocations. Randomization is a
      process by which subsequent subjects are enrolled into trial groups only by
      chance, which essentially eliminates selection biases. A serious consequence of
      randomization is severe imbalance among the treatment groups with respect to some
      prognostic factors, which invalidate the trial results or necessitate complex and
      usually unreliable secondary analysis to eradicate the source of imbalances.
      Minimization on the other hand tends to allocate in such a way as to minimize the
      differences among groups, with respect to prognostic factors. Pure minimization
      is therefore completely deterministic, that is, one can predict the allocation of
      the next subject by knowing the factor levels of a previously enrolled subject
      and having the properties of the next subject. To eliminate the predictability of
      randomization, it is necessary to include some elements of randomness in the
      minimization algorithms. In this article brief descriptions of randomization and
      minimization are presented followed by introducing selected randomization and
      minimization programs.

PMID- 22606660
TI  - A Brief Survey of Computational Models of Normal and Epileptic EEG Signals: A
      Guideline to Model-based Seizure Prediction.
AB  - In recent decades, seizure prediction has caused a lot of research in both signal
      processing and the neuroscience field. The researches have tried to enhance the
      conventional seizure prediction algorithms such that the rate of the false alarms
      be appropriately small, so that seizures can be predicted according to clinical
      standards. To date, none of the proposed algorithms have been sufficiently
      adequate. In this article we show that in considering the mechanism of the
      generation of seizures, the prediction results may be improved. For this purpose,
      an algorithm based on the identification of the parameters of a physiological
      model of seizures is introduced. Some models of electroencephalographic (EEG)
      signals that can also be potentially considered as models of seizure and some
      developed seizure models are reviewed. As an example the model of depth-EEG
      signals, proposed by Wendling, is studied and is shown to be a suitable model.

PMID- 22606662
TI  - Interdisciplinary researches in iran.

PMID- 22606663
TI  - R peak detection in electrocardiogram signal based on an optimal combination of
      wavelet transform, hilbert transform, and adaptive thresholding.
AB  - Electrocardiogram (ECG) is one of the most common biological signals which play a
      significant role in the diagnosis of heart diseases. One of the most important
      parts of ECG signal processing is interpretation of QRS complex and obtaining its
      characteristics. R wave is one of the most important sections of this complex,
      which has an essential role in diagnosis of heart rhythm irregularities and also
      in determining heart rate variability (HRV). This paper employs Hilbert and
      wavelet transforms as well as adaptive thresholding method to investigate an
      optimal combination of these signal processing techniques for the detection of R
      peak. In the experimental sections of this paper, the proposed algorithms are
      evaluated using both ECG signals from MIT-BIH database and synthetic data
      simulated in MATLAB environment with different arrhythmias, artifacts, and noise
      levels. Finally, by using wavelet and Hilbert transforms as well as by employing
      adaptive thresholding technique, an optimal combinational method for R peak
      detection namely WHAT is obtained that outperforms other techniques
      quantitatively and qualitatively.

PMID- 22606661
TI  - Review of fast monte carlo codes for dose calculation in radiation therapy
      treatment planning.
AB  - An important requirement in radiation therapy is a fast and accurate treatment
      planning system. This system, using computed tomography (CT) data, direction, and
      characteristics of the beam, calculates the dose at all points of the patient's
      volume. The two main factors in treatment planning system are accuracy and speed.
      According to these factors, various generations of treatment planning systems are
      developed. This article is a review of the Fast Monte Carlo treatment planning
      algorithms, which are accurate and fast at the same time. The Monte Carlo
      techniques are based on the transport of each individual particle (e.g., photon
      or electron) in the tissue. The transport of the particle is done using the
      physics of the interaction of the particles with matter. Other techniques
      transport the particles as a group. For a typical dose calculation in radiation
      therapy the code has to transport several millions particles, which take a few
      hours, therefore, the Monte Carlo techniques are accurate, but slow for clinical
      use. In recent years, with the development of the 'fast' Monte Carlo systems, one
      is able to perform dose calculation in a reasonable time for clinical use. The
      acceptable time for dose calculation is in the range of one minute. There is
      currently a growing interest in the fast Monte Carlo treatment planning systems
      and there are many commercial treatment planning systems that perform dose
      calculation in radiation therapy based on the Monte Carlo technique.

PMID- 22606664
TI  - Arrhythmia Detection based on Morphological and Time-frequency Features of T-wave
      in Electrocardiogram.
AB  - As the T-wave section in electrocardiogram (ECG) illustrates the repolarization
      phase of heart activity, the information which is accumulated in this section is
      so significant that it can explain the proper operation of electrical activities
      in heart. Long QT syndrome (LQT) and T-Wave Alternans (TWA) have imperceptible
      effects on time and amplitude of T-wave interval. Therefore, T-wave shapes of
      these diseases are similar to normal beats. Consequently, several T-wave features
      can be used to classify LQT and TWA diseases from normal ECGs. Totally, 22
      features including 17 morphological and 5 wavelet features have been extracted
      from T-wave to show the ability of this section to recognize the normal and
      abnormal records. This recognition can be implemented by pre-processing, T-wave
      feature extraction and artificial neural network (ANN) classifier using Multi
      Layer Perceptron (MLP). The ECG signals obtained from 142 patients (40 normal, 47
      LQT and 55 TWA) are processed and classified from MIT-BIH database. The
      specificity factor for normal, LQT, and TWA classifications are 99.89%, 99.90%,
      and 99.43%, respectively. T-wave features are one of the most important
      descriptors for LQT syndrome, Normal and TWA of ECG classification. The
      morphological features of T-wave have also more effect on the classification
      performance in LQT, TWA and normal samples compared with the wavelet features.

PMID- 22606665
TI  - A New Method for Pseudo-increasing Frame Rates of Echocardiography Images Using
      Manifold Learning.
AB  - Increasing frame rate is a challenging issue for better interpretation of medical
      images and diagnosis based on tracking the small transient motions of myocardium
      and valves in real time visualization. In this paper, manifold learning algorithm
      is applied to extract the nonlinear embedded information about echocardiography
      images from the consecutive images in two dimensional manifold spaces. In this
      method, we presume that the dimensionality of echocardiography images obtained
      from a patient is artificially high and the images can be described as functions
      of only a few underlying parameters such as periodic motion due to heartbeat. By
      this approach, each image is projected as a point on the reconstructed manifold;
      hence, the relationship between images in the new domain can be obtained
      according to periodicity of the heart cycle. To have a better tracking of the
      echocardiography, images during the fast motions of heart we have rearranged the
      similar frames of consecutive heart cycles in a sequence. This provides a full
      view slow motion of heart movement through increasing the frame rate to three
      times the traditional ultrasound systems.

PMID- 22606666
TI  - Structures of the recurrence plot of heart rate variability signal as a tool for
      predicting the onset of paroxysmal atrial fibrillation.
AB  - This paper aims to propose an effective paroxysmal atrial fibrillation (PAF)
      predictor which is based on the analysis of the heart rate variability (HRV)
      signal. Predicting the onset of PAF, based on non-invasive techniques, is
      clinically important and can be invaluable in order to avoid useless therapeutic
      interventions and to minimize the risks for the patients. This method consists of
      four steps: Preprocessing, feature extraction, feature reduction, and
      classification. In the first step, the QRS complexes are detected from the
      electrocardiogram (ECG) signal and then the HRV signal is extracted. In the next
      step, the recurrence plot (RP) of HRV signal is obtained and six features are
      extracted to characterize the basic patterns of the RP. These features consist of
      length of longest diagonal segments, average length of the diagonal lines,
      entropy, trapping time, length of longest vertical line, and recurrence trend. In
      the third step, these features are reduced to three features by the linear
      discriminant analysis (LDA) technique. Using LDA not only reduces the number of
      the input features, but also increases the classification accuracy by selecting
      the most discriminating features. Finally, a support vector machine-based
      classifier is used to classify the HRV signals. The performance of the proposed
      method in prediction of PAF episodes was evaluated using the Atrial Fibrillation
      Prediction Database which consists of both 30-minutes ECG recordings end just
      prior to the onset of PAF and segments at least 45 min distant from any PAF
      events. The obtained sensitivity, specificity, and positive predictivity were
      96.55%, 100%, and 100%, respectively.

PMID- 22606667
TI  - Application of MIMO Disturbance Observer to Control of an Electric Wheelchair
      Using NSGA-II.
AB  - Electric wheelchairs (EW) experience various terrain surfaces and slopes as well
      as occupants with diverse weights. This, in turn, imparts a substantial amount of
      perturbation to the EW dynamics. In this paper, we make use of a two-degree-of
      freedom control architecture called disturbance observer (DOB) which reduces
      sensitivity to model uncertainties, while enhancing rejection of disturbances
      caused due to entering slopes. The feedback loop which is designed via
      characteristic loci method is then augmented with a DOB with a parameterized low
      pass filter. According to disturbance rejection, sensitivity reduction, and noise
      rejection of the whole controller, three performance indices are defined which
      enable us to pick the filter's optimal parameters using a multi-objective
      optimization approach called non-dominated sorting genetic algorithm-II. Finally,
      experimental results show desirable improvement in stiffness and disturbance
      rejection of the proposed controller as well as its robust stability.

PMID- 22606668
TI  - EEG-based Drowsiness Detection for Safe Driving Using Chaotic Features and
      Statistical Tests.
AB  - Electro encephalography (EEG) is one of the most reliable sources to detect sleep
      onset while driving. In this study, we have tried to demonstrate that sleepiness
      and alertness signals are separable with an appropriate margin by extracting
      suitable features. So, first of all, we have recorded EEG signals from 10
      volunteers. They were obliged to avoid sleeping for about 20 hours before the
      test. We recorded the signals while subjects did a virtual driving game. They
      tried to pass some barriers that were shown on monitor. Process of recording was
      ended after 45 minutes. Then, after preprocessing of recorded signals, we labeled
      them by drowsiness and alertness by using times associated with pass times of the
      barriers or crash times to them. Then, we extracted some chaotic features
      (include Higuchi's fractal dimension and Petrosian's fractal dimension) and
      logarithm of energy of signal. By applying the two-tailed t-test, we have shown
      that these features can create 95% significance level of difference between
      drowsiness and alertness in each EEG channels. Ability of each feature has been
      evaluated by artificial neural network and accuracy of classification with all
      features was about 83.3% and this accuracy has been obtained without performing
      any optimization process on classifier.

PMID- 22606670
TI  - Segmentation of Multiple Sclerosis Lesions in Brain MR Images Using Spatially
      Constrained Possibilistic Fuzzy C-Means Classification.
AB  - This paper introduces a novel methodology for the segmentation of brain MS
      lesions in MRI volumes using a new clustering algorithm named SCPFCM. SCPFCM uses
      membership, typicality and spatial information to cluster each voxel. The
      proposed method relies on an initial segmentation of MS lesions in T1-w and T2-w
      images by applying SCPFCM algorithm, and the T1 image is then used as a mask and
      is compared with T2 image. The proposed method was applied to 10 clinical MRI
      datasets. The results obtained on different types of lesions have been evaluated
      by comparison with manual segmentations.

PMID- 22606669
TI  - IMPST: A New Interactive Self-Training Approach to Segmentation Suspicious
      Lesions in Breast MRI.
AB  - Breast lesion segmentation in magnetic resonance (MR) images is one of the most
      important parts of clinical diagnostic tools. Pixel classification methods have
      been frequently used in image segmentation with two supervised and unsupervised
      approaches up to now. Supervised segmentation methods lead to high accuracy, but
      they need a large amount of labeled data, which is hard, expensive, and slow to
      be obtained. On the other hand, unsupervised segmentation methods need no prior
      knowledge and lead to low performance. However, semi-supervised learning which
      uses not only a few labeled data, but also a large amount of unlabeled data
      promises higher accuracy with less effort. In this paper, we propose a new
      interactive semi-supervised approach to segmentation of suspicious lesions in
      breast MRI. Using a suitable classifier in this approach has an important role in
      its performance; in this paper, we present a semi-supervised algorithm improved
      self-training (IMPST) which is an improved version of self-training method and
      increase segmentation accuracy. Experimental results show that performance of
      segmentation in this approach is higher than supervised and unsupervised methods
      such as K nearest neighbors, Bayesian, Support Vector Machine, and Fuzzy c-Means.

PMID- 22606671
TI  - A New Markov Random Field Segmentation Method for Breast Lesion Segmentation in
      MR images.
AB  - Breast cancer is a major public health problem for women in the Iran and many
      other parts of the world. Dynamic contrast-enhanced magnetic resonance imaging
      (DCE-MRI) plays a pivotal role in breast cancer care, including detection,
      diagnosis, and treatment monitoring. But segmentation of these images which is
      seriously affected by intensity inhomogeneities created by radio-frequency coils
      is a challenging task. Markov Random Field (MRF) is used widely in medical image
      segmentation especially in MR images. It is because this method can model
      intensity inhomogeneities occurring in these images. But this method has two
      critical weaknesses: Computational complexity and sensitivity of the results to
      the models parameters. To overcome these problems, in this paper, we present
      Improved-Markov Random Field (I-MRF) method for breast lesion segmentation in MR
      images. Unlike the conventional MRF, in the proposed approach, we don't use the
      Iterative Conditional Mode (ICM) method or Simulated Annealing (SA) for class
      membership estimation of each pixel (lesion and non-lesion). The prior
      distribution of the class membership is modeled as a ratio of two conditional
      probability distributions in a neighborhood which is defined for each pixel:
      probability distribution of similar pixels and non-similar ones. Since our
      proposed approach don't use an iterative method for maximizing the posterior
      probability, above mentioned problems are solved. Experimental results show that
      performance of segmentation in this approach is higher than conventional MRF in
      terms of accuracy, precision, and Computational complexity.

PMID- 22606672
TI  - Enhancing P300 Wave of BCI Systems Via Negentropy in Adaptive Wavelet Denoising.
AB  - Brian Computer Interface (BCI) is a direct communication pathway between the
      brain and an external device. BCIs are often aimed at assisting, augmenting or
      repairing human cognitive or sensory-motor functions. EEG separation into target
      and non-target ones based on presence of P300 signal is of difficult task mainly
      due to their natural low signal to noise ratio. In this paper a new algorithm is
      introduced to enhance EEG signals and improve their SNR. Our denoising method is
      based on multi-resolution analysis via Independent Component Analysis (ICA)
      Fundamentals. We have suggested combination of negentropy as a feature of signal
      and subband information from wavelet transform. The proposed method is finally
      tested with dataset from BCI Competition 2003 and gives results that compare
      favorably.

PMID- 22606673
TI  - Reducing interpolation artifacts for mutual information based image registration.
AB  - Medical image registration methods which use mutual information as similarity
      measure have been improved in recent decades. Mutual Information is a basic
      concept of Information theory which indicates the dependency of two random
      variables (or two images). In order to evaluate the mutual information of two
      images their joint probability distribution is required. Several interpolation
      methods, such as Partial Volume (PV) and bilinear, are used to estimate joint
      probability distribution. Both of these two methods yield some artifacts on
      mutual information function. Partial Volume-Hanning window (PVH) and Generalized
      Partial Volume (GPV) methods are introduced to remove such artifacts. In this
      paper we show that the acceptable performance of these methods is not due to
      their kernel function. It's because of the number of pixels which incorporate in
      interpolation. Since using more pixels requires more complex and time consuming
      interpolation process, we propose a new interpolation method which uses only four
      pixels (the same as PV and bilinear interpolations) and removes most of the
      artifacts. Experimental results of the registration of Computed Tomography (CT)
      images show superiority of the proposed scheme.

PMID- 22606674
TI  - Denoising Medical Images using Calculus of Variations.
AB  - We propose a method for medical image denoising using calculus of variations and
      local variance estimation by shaped windows. This method reduces any additive
      noise and preserves small patterns and edges of images. A pyramid structure
      texture decomposition of images is used to separate noise and texture components
      based on local variance measures. The experimental results show that the proposed
      method has visual improvement as well as a better SNR, RMSE and PSNR than common
      medical image denoising methods. Experimental results in denoising a sample
      Magnetic Resonance image show that SNR, PSNR and RMSE have been improved by 19, 9
      and 21 percents respectively.

PMID- 22606675
TI  - Fully automatic lung segmentation and rib suppression methods to improve nodule
      detection in chest radiographs.
AB  - Computer-aided Diagnosis (CAD) systems can assist radiologists in several
      diagnostic tasks. Lung segmentation is one of the mandatory steps for initial
      detection of lung cancer in Posterior-Anterior chest radiographs. On the other
      hand, many CAD schemes in projection chest radiography may benefit from the
      suppression of the bony structures that overlay the lung fields, e.g. ribs. The
      original images are enhanced by an adaptive contrast equalization and non-linear
      filtering. Then an initial estimation of lung area is obtained based on
      morphological operations and then it is improved by growing this region to find
      the accurate final contour, then for rib suppression, we use oriented spatial
      Gabor filter. The proposed method was tested on a publicly available database of
      247 chest radiographs. Results show that this method outperformed greatly with
      accuracy of 96.25% for lung segmentation, also we will show improving the
      conspicuity of lung nodules by rib suppression with local nodule contrast
      measures. Because there is no additional radiation exposure or specialized
      equipment required, it could also be applied to bedside portable chest x-rays. In
      addition to simplicity of these fully automatic methods, lung segmentation and
      rib suppression algorithms are performed accurately with low computation time and
      robustness to noise because of the suitable enhancement procedure.

PMID- 22606676
TI  - A Comparison between the hp-version of Finite Element Method with EIDORS for
      Electrical Impedance Tomography.
AB  - In this study, a hp-version of Finite Element Method (FEM) was applied for
      forward modeling in image reconstruction of Electrical Impedance Tomography
      (EIT). The EIT forward solver is normally based on the conventional Finite
      Element Method (h-FEM). In h-FEM, the polynomial order (p) of the element shape
      functions is constant and the element size (h) is decreasing. To have an accurate
      simulation with the h-FEM, a mesh with large number of nodes and elements is
      usually needed. In order to overcome this problem, the high order finite element
      method (p-FEM) was proposed. In the p-version, the polynomial order is increasing
      and the mesh size is constant. Combining the advantages of two previously
      mentioned methods, the element size (h) was decreased and the polynomial order
      (p) was increased, simultaneously, which is called the hp-version of Finite
      Element Method (hp-FEM). The hp-FEM needs a smaller number of nodes and
      consequently, less computational time and less memory to achieve the same or even
      better accuracy than h-FEM. The SNR value is 42db for hp-FEM and is 9db for h
      FEM. The numerical results are presented and verified that the performance of the
      hp-version is better than of the h-version in image reconstruction of EIT.

PMID- 22606677
TI  - Sperm detection in video frames of semen sample using morphology and effective
      ellipse detection method.
AB  - CASA (Computer assisted semen analysis) systems are designed to assist
      Andrologist labour. Most available CASA systems are not accurate or so expensive.
      Therefore labours use manual methods to provide parameters. Although some
      companies have achieved appropriate accuracy, they have not released their
      methods. So proposing methods in this area might be useful for groups who intend
      to design new CASA system. One of the parameters which these systems compute is
      sperm count. In this paper we introduce our algorithm which can count sperms with
      an acceptable accuracy. Sperm count or concentration is one determinant parameter
      in male fertility. Our program preprocesses the video frame or image of semen
      sample under the microscope recorded by camera, then use morphology and effective
      ellipse detection method techniques to segment sperms and then count appropriate
      sperms.

PMID- 22606678
TI  - Compassion and cultural transformation in chronic pain.

PMID- 22606679
TI  - Evidence-based guideline for neuropathic pain interventional treatments: spinal
      cord stimulation, intravenous infusions, epidural injections and nerve blocks.
AB  - BACKGROUND: The Special Interest Group of the Canadian Pain Society has produced
      consensus-based guidelines for the pharmacological management of neuropathic
      pain. The society aimed to generate an additional guideline for other forms of
      neuropathic pain treatments. OBJECTIVE: To develop evidence-based recommendations
      for neuropathic pain interventional treatments. METHODS: A task force was created
      and engaged the Institute of Health Economics in Edmonton, Alberta, to survey the
      literature pertaining to multiple treatments. Sufficient literature existed on
      four interventions only: spinal cord stimulation; epidural injections;
      intravenous infusions; and nerve blocks. A comprehensive search was conducted for
      systematic reviews, randomized controlled trials and evidence-based clinical
      practice guidelines; a critical review was generated on each topic. A modified
      United States Preventive Services Task Force tool was used for quality rating and
      grading of recommendations. RESULTS: Investigators reviewed four studies of
      spinal cord stimulation, 19 studies of intravenous infusions, 14 studies of
      epidural injections and 16 studies of nerve blocks that met the inclusion
      criteria. The task force chairs rated the quality of evidence and graded the
      recommendations. Feedback was solicited from the members of the task force.
      CONCLUSION: There is sufficient evidence to support recommendations for some of
      these interventions for selected neuropathic pain conditions. This evidence is,
      at best, moderate and is often limited or conflicting. Pain practitioners are
      encouraged to explore evidence-based treatment options before considering
      unproven treatments. Full disclosure of risks and benefits of the available
      options is necessary for shared decision making and informed consent.

PMID- 22606680
TI  - Executive and attentional functions in chronic pain: does performance decrease
      with increasing task load?
AB  - BACKGROUND: Diminished executive function and attentional control has been
      reported in chronic pain patients. However, the precise pattern of impairment in
      these aspects of cognition in chronic pain remains unclear. Moreover, a decline
      in psychomotor speed could potentially influence executive and attentional
      control performance in pain patients. OBJECTIVE: To examine different aspects of
      executive and attentional control in chronic pain together with the confounding
      role of psychomotor slowing. METHODS: Neuropsychological tests of sustained
      attention, planning ability, inhibition and mental flexibility were administered
      to 34 participants with chronic pain and 32 control participants. RESULTS:
      Compared with the controls, participants with chronic pain took longer to
      complete tests of sustained attention and mental flexibility, but did not perform
      worse on inhibition or planning tasks. The decreased performance on the mental
      flexibility task likely reflects a reduction in psychomotor speed. The pattern of
      performance on the sustained attention task reveals a specific decline in
      attention, indicated by a disproportionate decline in performance with an
      increase in task duration and by increased fluctuations in attention during task
      performance. No additional effect was noted of pain intensity, pain duration,
      pain catastrophizing, depressive symptoms, reduced sleep because of the pain or
      opioid use. CONCLUSIONS: Executive and attention functions are not uniformly
      affected in chronic pain. At least part of the previously reported decline in
      executive function in this group may reflect psychomotor slowing. Overall,
      limited evidence was found that executive and attention performance is indeed
      lower in chronic pain. Therefore, it can be concluded that in chronic pain
      sustained attention performance is diminished while mental flexibility, planning
      and inhibition appear to be intact.

PMID- 22606681
TI  - The epidemiology of chronic pain in Canadian men and women between 1994 and 2007:
      longitudinal results of the National Population Health Survey.
AB  - BACKGROUND: The epidemiology of chronic pain is poorly understood due to a
      paucity of longitudinal studies limiting the ability to develop prevention
      strategies for a condition resistant to many current therapies. OBJECTIVES: To
      identify the incidence of and sociodemographic risk factors for chronic pain in
      Canadian women and men over a 12-year period. METHODS: Using data from the
      National Population Health Survey, individuals who developed chronic pain,
      defined as the presence of "usual pain" were identified. The cumulative incidence
      of chronic pain was calculated separately for men and women followed from 1994 to
      2007. Biannual incidence and prevalence estimates of chronic pain were calculated
      during the same time period. Logistic regression analysis was used to examine
      predictors of chronic pain in men and women. RESULTS: The cumulative incidence
      over the 12-year period was 35.6% (women 39.0%; men 32.2%). Women had a higher
      biannual prevalence, but not incidence, of chronic pain compared with men. In
      women, being older, having lower education and being widowed, separated or
      divorced, increased the risk of chronic pain. There were no sociodemographic risk
      factors for chronic pain in men. CONCLUSION: Women had a higher prevalence - but
      not incidence - of chronic pain compared with men, indicative of longer duration
      of illness in women. Risk factors also differed according to sex, supporting
      current literature reporting potentially different mechanisms for men and women.
      A better understanding of risk factors is necessary to develop population-based
      preventive interventions. The former can only be achieved with population-based,
      longitudinal studies.

PMID- 22606682
TI  - Improvements in pain outcomes in a Canadian pediatric teaching hospital following
      implementation of a multifaceted knowledge translation initiative.
AB  - BACKGROUND: A previous audit performed at a tertiary / quaternary pediatric
      hospital in Toronto, Ontario, demonstrated suboptimal assessment and treatment of
      children's pain. Knowledge translation (KT) initiatives (education, reminders,
      audit and feedback) were implemented to address identified care gaps; however,
      the impact is unknown. OBJECTIVES: To determine the impact of KT initiatives on
      pain outcomes including process outcomes (eg, pain assessment and management
      practices) and clinical outcomes (eg, pain prevalence and intensity); and to
      benchmark additional pain practices, particularly opioid administration and
      painful procedures. METHODS: Medical records at The Hospital for Sick Children
      (Toronto, Ontario) were reviewed on a single day in September 2007. Pain
      assessment and management practices, and pain prevalence and intensity in the
      preceding 24 h were recorded on a standardized data collection form. Where
      possible, pain outcomes were compared with previous audit results. RESULTS:
      Records of 265 inpatients were audited. Sixty-three per cent of children
      underwent a documented pain assessment compared with 27% in an audit conducted
      previously (P<0.01). Eighty-three per cent of children with documented pain
      received at least one pain management intervention. Overall, 51% of children
      received pharmacological therapy, and 15% received either a psychological or
      physical pain-relieving intervention. Of those assessed, 44% experienced pain in
      the previous 24 h versus 66% in the previous audit (P<0.01). Fewer children
      experienced severe pain compared with the first audit (8.7% versus 26.1%;
      P<0.01). One-third of children received opioids; 19% of these had no recorded
      pain assessment. Among 131 children who underwent a painful procedure, 21% had a
      concurrent pain assessment. Painful procedures were accompanied by a pain
      relieving intervention in 12.5% of cases. CONCLUSIONS: Following KT initiatives,
      significant improvements in pain processes (pain assessment documentation and
      pain management interventions) and clinical outcomes (pain prevalence, pain
      intensity) were observed. Further improvements are recommended, specifically with
      respect to procedural pain practices and opioid utilization patterns.

PMID- 22606684
TI  - Elimination of suction effect in interfacing microchip electrophoresis with
      inductively coupled plasma mass spectrometry using porous monolithic plugs.
AB  - A suction-free interfacing method was developed for microchip electrophoresis
      hyphenated with inductively coupled plasma mass spectrometry (MCE-ICP-MS). The
      hyphenated system was composed of a microchip, a demountable capillary microflow
      nebulizer (d-CMN) combined with a heated single pass spray chamber, a negative
      pressure sampling device, a high voltage power supply, a syringe pump and an ICP
      MS. To eliminate the nebulizer suction generated by the pneumatic nebulizer and
      to ensure that the makeup solution flowed into the nebulizer, two porous polymer
      plugs were fabricated in the microchip. As a result, reasonably true
      electropherograms were obtained when compared to the CE separation performed in
      the traditional MCE-ICP-MS mode without porous polymer plugs. Electrophoretic
      separation of I(-) and IO(3)(-) was achieved within 25 s in a microchip with an
      effective separation length of only 15 mm at an electric field of 857 V cm(-1)
      using 10 mmol L(-1) borate (pH 9.2) as the running buffer. A resolution of 1.3
      was obtained and the absolute detection limits for I(-) and IO(3)(-) were 0.12
      and 0.13 fg, respectively. The precisions (RSD, n = 10) of the migration time and
      peak height for I(-) and IO(3)(-) were in the range of 1.1-1.6% and 2.5-2.8%,
      respectively. Two table salt samples were analyzed by an external calibration
      method. The iodate contents were in accordance with their labeled values. The
      recoveries of I(-) and IO(3)(-) in the table salt samples were in the range of 92
      105%.

PMID- 22606683
TI  - Direct analysis of steviol glycosides from Stevia leaves by ambient ionization
      mass spectrometry performed on whole leaves.
AB  - Leaf spray mass spectrometry is explored as a fast and simple way for direct
      analysis of sweet glycosides in fresh untreated Stevia leaves without sample
      pretreatment. In this technique, a fresh triangular piece of Stevia leaf serves
      as both sample and substrate. Application of a butanol : methanol : water mixture
      and a high voltage to intact leaf material produces a high electric field at the
      tip of the leaf. This results in field emission of charged droplets containing
      the glycosides. The resulting dry ions are detected by mass spectrometry and
      confirmed by tandem mass spectrometry and exact mass measurements. A comparison
      between leaf spray and other ambient ionization methods which are successful for
      screening glycosides in Stevia leaves--desorption electrospray ionization, low
      temperature plasma and paper spray--shows that leaf spray produces the highest
      quality spectra. It is also extremely easy to implement with no need for
      nebulizing gas or sample preparation and is suited to semi-quantitative
      determinations. The potential for the application of leaf spray mass spectrometry
      to direct and rapid screening of plant materials is here realized in the case of
      Stevia sweet glycosides.

PMID- 22606685
TI  - Detection of the cell viability and proliferation using two-signal
      electrochemical method.
AB  - Two electrochemical signals of the MCF-7 cell were simultaneously detected by
      using multiwall carbon nanotubes and room temperature ionic liquid composite film
      modified electrode. The signal at +0.726 V due to the oxidation of xanthine and
      guanine, was obviously improved. And the signal at +1.053 V due to the oxidation
      of hypoxanthine and adenine was found for the first time. This two-signal
      electrochemical method is credible to detect cell viability and proliferation.

PMID- 22606687
TI  - Ultra-low level optical detection of mercuric ions using biogenic gold
      nanotriangles.
AB  - Mercury is a serious environmental pollutant known to have detrimental health
      effects in all life forms. Here, we report the use of biologically synthesized
      aqueous gold nanotriangles for sensitive and selective optical detection of femto
      molar levels of mercury ions by exploiting the high amalgamation tendency of
      mercury metal towards gold. Aqueous chloroaurate ions were reduced using
      lemongrass (Cymbopogon flexuosus) leaf extract at room temperature to form gold
      nanotriangles. Mercuric (Hg(2+)) ions were reduced in the presence of these
      triangles to facilitate amalgamation and the optical properties were monitored.
      We observe a significant change in the longitudinal plasmon absorption band of
      the nanotriangles even at femto-molar concentrations of mercuric ions. High
      resolution transmission electron microscopy confirms changes in particle
      morphology at such low concentrations. This protocol shows no sensitivity to
      other environmentally relevant metal ions, including Pb(2+), Zn(2+), Cd(2+),
      Fe(2+), Ni(2+), Sr(2+), Ca(2+), Mn(2+), and Cu(2+), confirming further that
      change in the optical properties of gold nanotriangles in the presence of reduced
      mercuric ions is solely due to the strong amalgamation tendency of mercury metal.

PMID- 22606686
TI  - Highly sensitive and selective analysis of urinary steroids by comprehensive two
      dimensional gas chromatography combined with positive chemical ionization
      quadrupole mass spectrometry.
AB  - Comprehensive two dimensional gas chromatography (GC * GC) provides greater
      separation space than conventional GC. Because of fast peak elution, a time of
      flight mass spectrometer (TOFMS) is the usual structure-specific detector of
      choice. The quantitative capabilities of a novel GC * GC fast quadrupole MS were
      investigated with electron ionization (EI), and CH(4) or NH(3) positive chemical
      ionization (PCI) for analysis of endogenous urinary steroids targeted in anti
      doping tests. Average precisions for steroid quantitative analysis from replicate
      urine extractions were 6% (RSD) for EI and 8% for PCI-NH(3). The average limits
      of detection (LODs) calculated by quantification ions for 12 target steroids
      spiked into steroid-free urine matrix (SFUM) were 2.6 ng mL(-1) for EI, 1.3 ng
      mL(-1) for PCI-CH(4), and 0.3 ng mL(-1) for PCI-NH(3), all in mass scanning mode.
      The measured limits of quantification (LOQs) with full mass scan GC * GC-qMS were
      comparable with the LOQ values measured by one-dimensional GC-MS in selected ion
      monitoring (SIM) mode. PCI-NH(3) yields fewer fragments and greater
      (pseudo)molecular ion abundances than EI or PCI-CH(4). These data show that a
      benchtop GC * GC-qMS system has the sensitivity, specificity, and resolution to
      analyze urinary steroids at normal urine concentrations, and that PCI-NH(3), not
      currently available on most GC * GC-TOFMS instruments, is of particular value for
      generation of structure-specific ions.

PMID- 22606688
TI  - Nafion-CNT coated carbon-fiber microelectrodes for enhanced detection of
      adenosine.
AB  - Adenosine is a neuromodulator that regulates neurotransmission. Adenosine can be
      monitored using fast-scan cyclic voltammetry at carbon-fiber microelectrodes and
      ATP is a possible interferent in vivo because the electroactive moiety, adenine,
      is the same for both molecules. In this study, we investigated carbon-fiber
      microelectrodes coated with Nafion and carbon nanotubes (CNTs) to enhance the
      sensitivity of adenosine and decrease interference by ATP. Electrodes coated in
      0.05 mg mL(-1) CNTs in Nafion had a 4.2 +/- 0.2 fold increase in current for
      adenosine, twice as large as for Nafion alone. Nafion-CNT electrodes were 6 times
      more sensitive to adenosine than ATP. The Nafion-CNT coating did not slow the
      temporal response of the electrode. Comparing different purine bases shows that
      the presence of an amine group enhances sensitivity and that purines with
      carbonyl groups, such as guanine and hypoxanthine, do not have as great an
      enhancement after Nafion-CNT coating. The ribose group provides additional
      sensitivity enhancement for adenosine over adenine. The Nafion-CNT modified
      electrodes exhibited significantly more current for adenosine than ATP in brain
      slices. Therefore, Nafion-CNT modified electrodes are useful for sensitive,
      selective detection of adenosine in biological samples.

PMID- 22606690
TI  - Coupling laser ablation/desorption electrospray ionization to atmospheric
      pressure drift tube ion mobility spectrometry for the screening of antimalarial
      drug quality.
AB  - Significant developments in the field of ambient desorption/ionization mass
      spectrometry (MS) have led to high-throughput direct analysis and imaging
      capabilities. However, advances in coupling ambient ionization techniques with
      standalone drift tube ion mobility spectrometry (DTIMS) have been comparatively
      slower, despite the attractive ruggedness and simplicity of IMS. In this study,
      we have developed and characterized a laser ablation/desorption electrospray
      ionization (LADESI) DTIMS platform, and applied it to the detection of active
      pharmaceutical ingredients (APIs) in antimalarial tablets collected in developing
      countries. The overarching goal of this work was to perform an initial evaluation
      of LADESI DTIMS as a technique with the potential for constituting the core of a
      portable drug quality-testing platform. The set-up consisted of an IR laser for
      desorption and an electrospray ionizer for capturing the ablated plume coupled to
      a high-resolution monolithic resistive glass drift tube ion mobility
      spectrometer. For more confident API identification, tablet extracts were also
      investigated via electrospray IM MS to correlate LADESI DTIMS reduced mobility
      (K(0)) values to m/z values. Overall, it was found that the IR LADESI DTIMS
      platform provided distinct ion mobility spectral fingerprints that could be used
      to detect the presence of the expected APIs, helping to distinguish counterfeit
      drugs from their genuine counterparts.

PMID- 22606689
TI  - Simplified sheath flow cuvette design for ultrasensitive laser induced
      fluorescence detection in capillary electrophoresis.
AB  - We present a design for a sheath-flow cuvette that uses a relatively inexpensive
      quartz cuvette. The cuvette has a high optical quality square flow chamber that
      is fused to quartz tubes at each end. PEEK/TEFZEL fittings hold and seal the
      quartz flow chamber without putting strain on the cuvette. The performance of the
      cuvette is evaluated as a laser-induced fluorescence detector for capillary
      electrophoresis. The cuvette produces mass detection limits of 50 yoctomoles (30
      copies) for 5-carboxyl tetramethylrhodamine (5 TAMRA SE) with a separation
      efficiency of 400,000 theoretical plates.

PMID- 22606691
TI  - A chiral phenoxyamine magnesium catalyst for the enantioselective
      hydroamination/cyclization of aminoalkenes and intermolecular hydroamination of
      vinyl arenes.
AB  - If Grignard had only known! A chiral magnesium complex catalyzes the
      intramolecular hydroamination/cyclization of aminoalkenes with high efficiency at
      temperatures as low as -20  degrees C and enantioselectivities as high as 93 %
      ee. The high activity of this system also allows the catalytic intermolecular
      anti-Markovnikov addition of pyrrolidine and benzylamine to vinyl arenes.

PMID- 22606693
TI  - Retraction. S-Allyl-L-cysteine sulfoxide inhibits tumor necrosis factor-alpha
      induced monocyte adhesion and intercellular cell adhesion molecule-1 expression
      in human umbilical vein endothelial cells.

PMID- 22606692
TI  - Getting to done. By Caveman.

PMID- 22606694
TI  - Bibliography. Genitourinary system. Current world literature.

PMID- 22606695
TI  - Bibliography. Innovative early clinical trials methodology and new therapeutics
      in cancer. Current world literature.

PMID- 22606696
TI  - Cost-effectiveness of fluorescent cystoscopy for noninvasive papillary tumors:
      con.

PMID- 22606697
TI  - Abstracts of the 46th Annual Meeting of the Association for European Paediatric
      and Congenital Cardiology with joint sessions with the Japanese Society of
      Pediatric Cardiology and Cardiac Surgery. Istanbul, Turkey. May 23-26, 2012.

PMID- 22606698
TI  - Toll-like receptor 3 contributes to spinal glial activation and tactile allodynia
      after nerve injury.

PMID- 22606699
TI  - [Physician patient relationship - father or parent?].

PMID- 22606700
TI  - Abstracts of the 12th International Child Neurology Congress and the 11th Asian
      and Oceanian Congress of Child Neurology. May 27-June 1, 2012. Brisbane,
      Australia.

PMID- 22606701
TI  - [Decision of the Munchen OLG November 03 2011, AZ: 1 U 984/11 - complaint after
      dissatisfaction with the esthetic outcome of reconstructive procedure].

PMID- 22606702
TI  - Abstracts of the 6th Biennial Conference of the Australasian Academy of Cerebral
      Palsy & Developmental Medicine. May 30-June 2, 2012. Brisbane, Australia.

PMID- 22606703
TI  - Injectable hydrogel for sustained protein release by salt-induced association of
      hyaluronic acid nanogel.
AB  - A hyaluronic acid-based anionic nanogel formed by self-assembly of cholesteryl
      group-bearing HA is designed for protein delivery. The HA nanogel spontaneously
      binds various types of proteins without denaturation, such as recombinant human
      growth hormone, erythropoietin, exendin-4, and lysozyme. The HA nanogel shows
      unique colloidal properties, in particular that an injectable hydrogel is formed
      by salt-induced association of the HA nanogel. A pharmacokinetic study in rats
      shows that an in situ gel formulation, prepared by simply mixing rhGH and HA
      nanogel in phosphate buffer, maintains plasma rhGH levels within a narrow range
      over one week. Therefore, HA nanogels offer a simple method for easy formulation
      of therapeutic proteins and are effective for sustained protein release systems.

PMID- 22606704
TI  - Amphiphilic cholic-acid-modified dextran sulfate and its application for the
      controlled delivery of superoxide dismutase.
AB  - A novel amphiphilic and biodegradable polyelectrolyte DS-CA is prepared by the
      esterification of DS with CA. DS-CA can self-assemble into stable nanoparticles
      in water. SOD can effectively associate with DS-CA at pH = 5.0 by virtue of
      electrostatic and hydrophobic interactions. SOD release from the complex
      nanoparticles is slow at pH = 1.2. The release at pH = 7.4 PBS shows an extended
      behavior and is tunable by changing the weight ratio of SOD to DS-CA as well as
      the CA substitution degree. Increasing the CA substitution degree of DS-CA can
      significantly enhance the cellular uptake of the loaded SOD. This study
      demonstrates that the amphiphilic DS-CA provides a promising strategy for oral
      delivery of protein/peptide drugs.

PMID- 22606706
TI  - Study links oral care to lower diabetes costs.

PMID- 22606705
TI  - Controlled/living surface-initiated ATRP of antifouling polymer brushes from gold
      in PBS and blood sera as a model study for polymer modifications in complex
      biological media.
AB  - The use of PBS, 10% FBS or 10% CS as media for SI-ATRP is reported.
      Controlled/living SI-ATRP of MeOEGMA in PBS is achieved leading to better control
      than in water. The livingness is confirmed by chain extension with MeOEGMA or
      carboxybetaine acrylamide. This technique is successfully adopted for the
      polymerization of MeOEGMA in 10% FBS or CS as models for complex biological media
      with reasonable control of the brush growth. All prepared brushes show excellent
      antifouling properties.

PMID- 22606707
TI  - Feminism's fandango with the state revisited: reflections on Australia, feminism,
      education, and change.

PMID- 22606709
TI  - Gender implications of the "new" economic policy: a conceptual overview.

PMID- 22606711
TI  - [Summary of agricultural scientific research in    Taiwan, 1895-1945].

PMID- 22606712
TI  - [Wu Zhonglun's "Diary of Investigation on Plants in Yunnan"].

PMID- 22606714
TI  - Gender, familism and housing: matrimonial property rights in Ireland.

PMID- 22606715
TI  - Medicare program; changes to the Medicare Advantage and the Medicare prescription
      drug benefit programs for contract year 2013 and other changes. Final rule with
      comment period.
AB  - This final rule with comment period revises the Medicare Advantage (MA) program
      (Part C) regulations and prescription drug benefit program (Part D) regulations
      to implement new statutory requirements; strengthen beneficiary protections;
      exclude plan participants that perform poorly; improve program efficiencies; and
      clarify program requirements. It also responds to public comments regarding the
      long-term care facility conditions of participation pertaining to pharmacy
      services.

PMID- 22606716
TI  - Payment or reimbursement for emergency services for nonservice-connected
      conditions in non-VA facilities. Final rule.
AB  - This document amends the Department of Veterans Affairs (VA) ''Payment or
      Reimbursement for Emergency Services for Nonservice-Connected Conditions in Non
      VA Facilities'' regulations to conform with a statutory change that expanded
      veterans' eligibility for reimbursement. Some of the revisions in this final rule
      are purely technical, matching the language of our regulations to the language of
      the revised statute, while others set out VA's policies regarding the
      implementation of statutory requirements. This final rule expands the
      qualifications for payment or reimbursement to veterans who receive emergency
      services in non-VA facilities, and establishes accompanying standards for the
      method and amount of payment or reimbursement.

PMID- 22606717
TI  - World Trade Center Health Program requirements for the addition of new WTC
      related health conditions. Final rule.
AB  - Title I of the James Zadroga 9/11 Health and Compensation Act of 2010 amended the
      Public Health Service Act (PHS Act) to establish the World Trade Center (WTC)
      Health Program. Sections 3311, 3312, and 3321 of Title XXXIII of the PHS Act
      require that the WTC Program Administrator develop regulations to implement
      portions of the WTC Health Program established within the Department of Health
      and Human Services (HHS). The WTC Health Program, which is administered by the
      Director of the National Institute for Occupational Safety and Health (NIOSH),
      within the Centers for Disease Control and Prevention (CDC), provides medical
      monitoring and treatment to eligible firefighters and related personnel, law
      enforcement officers, and rescue, recovery and cleanup workers who responded to
      the September 11, 2001, terrorist attacks in New York City, Shanksville, PA, and
      at the Pentagon, and to eligible survivors of the New York City attacks. This
      final rule establishes the processes by which the WTC Program Administrator may
      add a new condition to the list of WTC-related health conditions through
      rulemaking, including a process for considering petitions by interested parties
      to add a new condition.

PMID- 22606718
TI  - Medicare and Medicaid programs; changes in provider and supplier enrollment,
      ordering and referring, and documentation requirements; and changes in provider
      agreements. Final rule.
AB  - This final rule finalizes several provisions of the Affordable Care Act
      implemented in the May 5, 2010 interim final rule with comment period. It
      requires all providers of medical or other items or services and suppliers that
      qualify for a National Provider Identifier (NPI) to include their NPI on all
      applications to enroll in the Medicare and Medicaid programs and on all claims
      for payment submitted under the Medicare and Medicaid programs. In addition, it
      requires physicians and other professionals who are permitted to order and
      certify covered items and services for Medicare beneficiaries to be enrolled in
      Medicare. Finally, it mandates document retention and provision requirements on
      providers and supplier that order and certify items and services for Medicare
      beneficiaries.

PMID- 22606719
TI  - Amendments to sterility test requirements for biological products. Final rule.
AB  - The Food and Drug Administration (FDA) is amending the sterility test
      requirements for biological products. This rule provides manufacturers of
      biological products greater flexibility, as appropriate, and encourages use of
      the most appropriate and state-of-the-art test methods for assuring the safety of
      biological products. FDA is taking this action as part of its ongoing efforts to
      comprehensively review and, as necessary, revise its regulations related to
      biological products.

PMID- 22606720
TI  - New woman, new world: maternal feminism and the new imperialism in the white
      settler colonies.

PMID- 22606721
TI  - Technical revisions to update reference to the required assessment tool for state
      nursing homes receiving per diem payments from VA. Final rule.
AB  - This rule updates the reference to the required resident assessment tool for
      State homes that receive per diem from VA for providing nursing home care to
      veterans. It requires State nursing homes receiving per diem from VA to use the
      most recent version of the Centers for Medicare and Medicaid Services (CMS)
      Resident Assessment Instrument/Minimum Data Set (MDS), which is version 3.0. This
      will ensure that the standard used to assess veterans is the same as the standard
      applicable to Medicare and Medicaid beneficiaries.

PMID- 22606722
TI  - No more library classes for Catherine: marital status, career progression and
      library employment in 1950s England.

PMID- 22606723
TI  - The "Women's International Sports Movement": local-global strategies and
      empowerment.

PMID- 22606724
TI  - The seeds of socialist ideology: women's experiences in Beishadao village.

PMID- 22606725
TI  - Medicaid program; Community First Choice option. Final rule.
AB  - This final rule implements section 2401 of the Affordable Care Act, which
      establishes a new State option to provide home and community-based attendant
      services and supports. These services and supports are known as Community First
      Choice (CFC). While this final rule sets forth the requirements for
      implementation of CFC, we are not finalizing the section concerning the CFC
      setting.

PMID- 22606726
TI  - Turkish women's predicament.

PMID- 22606727
TI  - Twenty-five years of Mexican feminisms.

PMID- 22606729
TI  - Labeling and effectiveness testing; sunscreen drug products for over-the-counter
      human use; delay of compliance dates. Final rule; delay of compliance dates;
      request for comments.
AB  - The Food and Drug Administration (FDA) is delaying the compliance dates for the
      final rule for over-the-counter (OTC) sunscreen drug products that published in
      the Federal Register of June 17, 2011 (76 FR 35620). The final rule establishes
      labeling and effectiveness testing for certain OTC sunscreen products containing
      specified active ingredients and marketed without approved applications. It also
      amends labeling claims that are not currently supported by data and lifts the
      previously-published delay of implementation of the Drug Facts labeling
      requirements for OTC sunscreens. The 2011 final rule's compliance dates are being
      delayed because information received after publication of the 2011 final rule
      indicates that full implementation of the 2011 final rule's requirements for all
      affected products will require an additional 6 months. This final rule is part of
      FDA's ongoing review of OTC drug products.

PMID- 22606730
TI  - Women's agency and survival strategies during the Holocaust.

PMID- 22606731
TI  - Copayments for medications in 2012. Final rule.
AB  - This document affirms as final, without change, an interim final rule amending
      the Department of Veterans Affairs (VA) medical regulations concerning the
      copayment required for certain medications. The interim final rule froze until
      December 31, 2012, the copayment amount for veterans in the VA health care system
      in enrollment priority categories 2 through 6 at the 2011 level, which was $8.
      The interim final rule also froze until December 31, 2012, the maximum annual
      copayment amount for enrollment priority categories 2 through 6, which was $960.
      On January 1, 2013, the copayment amounts may increase based on the prescription
      drug component of the Medical Consumer Price Index (CPI-P). If the copayment
      increases, the maximum annual copayment amount will automatically increase in
      turn.

PMID- 22606732
TI  - Reconsidering trauma, identity, and the African diaspora: enslavement and
      historical memory in nineteenth-century highland Madagascar.

PMID- 22606734
TI  - Medical loss ratio requirements under the Patient Protection and Affordable Care
      Act. Final rule.
AB  - This final rule amends the regulations implementing medical loss ratio (MLR)
      standards for health insurance issuers under the Public Health Service Act in
      order to establish notice requirements for issuers in the group and individual
      markets that meet or exceed the applicable MLR standard in the 2011 MLR reporting
      year.

PMID- 22606735
TI  - An "awful woman"? The life and work of Mrs Bridges Adams, 1855-1939.

PMID- 22606736
TI  - Attitudes to marriage and prostitution in the writings of Olive Schreiner, Mona
      Caird, Sarah Grand and George Egerton.

PMID- 22606737
TI  - Medicare and Medicaid program; regulatory provisions to promote program
      efficiency, transparency, and burden reduction. Final rule.
AB  - This final rule identifies reforms in Medicare and Medicaid regulations that CMS
      has identified as unnecessary, obsolete, or excessively burdensome on health care
      providers and beneficiaries. This rule increases the ability of health care
      professionals to devote resources to improving patient care, by eliminating or
      reducing requirements that impede quality patient care or that divert providing
      high quality patient care. This is one of several rules that we are finalizing to
      achieve regulatory reforms under Executive Order 13563 on Improving Regulation
      and Regulatory Review and the Department's Plan for Retrospective Review of
      Existing Rules.

PMID- 22606738
TI  - Medicare and Medicaid programs; reform of hospital and critical access hospital
      conditions of participation. Final rule.
AB  - This final rule revises the requirements that hospitals and critical access
      hospitals (CAHs) must meet to participate in the Medicare and Medicaid programs.
      These changes are an integral part of our efforts to reduce procedural burdens on
      providers. This rule reflects the Centers for Medicare and Medicaid Services'
      (CMS) commitment to the general principles of the President's Executive Order
      13563, released January 18, 2011, entitled "Improving Regulation and Regulatory
      Review.''

PMID- 22606739
TI  - Pay-for-performance programs to reduce racial/ethnic disparities: limitations of
      a one-size-fits-all approach.

PMID- 22606741
TI  - Autobiography, biography and Ford Madox Ford's women.

PMID- 22606742
TI  - Childbearers as rights-bearers: feminist discourse on the rights of Aboriginal
      and non-Aboriginal mothers in Australia, 1920-50.

PMID- 22606743
TI  - [Prediction of neurological prognosis after cardiac arrest-editorial].

PMID- 22606744
TI  - [The importance of NGAL and cystatin C biomarkers in cardiovascular diseases
      editorial].

PMID- 22606745
TI  - [Gastrin without a gastrinoma-editorial].

PMID- 22606746
TI  - Herophilus of Chalcedon and the Hippocratic tradition in early Alexandrian
      medicine.
AB  - Herophilus of Chalcedon (c. 330-250 BC) is famous as one of the leading figures
      in the development of medicine in Ptolemaic Alexandria around the first half of
      the third century BC. However, his medical science seems to have intrinsic
      continuity of thought with Hippocratic medicine. Herophilus followed the medical
      principle formulated in the Hippocratic treatise "On the Nature of Man," when he
      made his methodological pronouncement to the effect that primary parts of the
      human body should be perceptible by the senses. Herophilus rejected
      cardiocentrism, introduced by his teacher Praxagoras into the medical school of
      Cos, and returned to Hippocratic encephalocentrism, as represented by the author
      of the Hippocratic treatise "On the Sacred Disease." Herophilus differentiated
      between the faculties of the soul and the ones attributed to the nature. In his
      differentiation between these two faculties, Herophilus probably had in mind the
      Hippocratic conception of nature as specifically applied to the domain of the
      human body, as distinct from the soul. Herophilus' commitment to Hippocratic
      medicine is confirmed by his literary works on some of the Hippocratic texts. It
      is probable that Herophilus regarded himself as a more faithful successor than
      his teacher to the tradition of Hippocratic medicine. His anatomical research on
      the structure and function of the brain, motivated by his loyalty to the
      Hippocratic tradition, led him to innovative contributions to the development of
      medicine.

PMID- 22606747
TI  - Women's translations of scientific texts in the 18th century: a case study of
      Marie-Anne Lavoisier.
AB  - In the 18th century, many outstanding translations of scientific texts were done
      by women. These women were important mediators of science. However, I would like
      to raise the issue that the 'selection,' which is the process by which
      intellectual women chose to conduct translation works, and those 'selections'
      made by male translators, would not be made at the same level. For example,
      Emilie du Chatelet (1706-1749), the only French translator of Newton's
      "Principia," admitted her role as participating in important work, but, still,
      she was not perfectly satisfied with the position. For du Chatelet, the role as a
      translator was only an option under the current conditions that a female was
      denied the right to be a creator by society. In the case of Marie-Anne Lavoisier
      (1743-1794), like du Chatelet, we find an acute feeling in her mind that
      translation was not the work of creators. Because of her respect toward creative
      geniuses and her knowledge about the practical situation and concrete results of
      scientific studies, the translation works done by Marie-Anne Lavoisier were
      excellent. At the same time, the source of this excellence appears paradoxical at
      a glance: this excellence of translation was related closely with her low self
      estimation in the field of science. Hence, we should not forget the gender
      problem that is behind such translations of scientific works done by women in
      that era. Such a possibility was a ray of light that was grasped by females, the
      sign of a gender that was eliminated from the center of scientific study due to
      social systems and norms and one of the few valuable opportunities to let people
      know of her own existence in the field of science.

PMID- 22606748
TI  - Childbearing and infancy in the Carolingian world.

PMID- 22606749
TI  - Christianization, female infanticide, and the abundance of female burials at
      Viking Age Birka in Sweden.

PMID- 22606750
TI  - Pregnancy and childbirth in twelfth- and thirteenth-century French and English
      law.

PMID- 22606751
TI  - Of vanishing fetuses and maidens made-again: abortion, restored virginity, and
      similar scenarios in medieval Irish hagiography and penitentials.

PMID- 22606752
TI  - Childbirth miracles in Swedish miracle collections.

PMID- 22606753
TI  - Mothers and the martyr: the unlikely patronage of a medieval Dominican preacher.

PMID- 22606755
TI  - Japan's SAT?

PMID- 22606754
TI  - A marble embryo: meanings of a portrait from 1900.

PMID- 22606756
TI  - Preventing the hostile use of the life sciences and biotechnologies: fostering a
      culture of biosecurity and dual use awareness. Introduction.

PMID- 22606757
TI  - A life scientist, an engineer and a social scientist walk into a lab: challenges
      of dual-use engagement and education in synthetic biology.
AB  - The discussion of dual-use education is often predicated on a discrete population
      of practicing life scientists exhibiting certain deficiencies in awareness or
      expertise. This has lead to the claim that there is a greater requirement for
      awareness raising and education amongst this population. However, there is yet to
      be an inquiry into the impact of the 'convergent' nature of emerging techno
      sciences upon the prospects of dual-use education. The field of synthetic
      biology, although often portrayed as homogeneous, is in fact composed of various
      sub-fields and communities. Its practitioners have diverse academic backgrounds.
      The research institutions that have fostered its development in the UK often have
      their own sets of norms and practices in engagement with ethical, legal and
      social issues associated with scientific knowledge and technologies. The area is
      also complicated by the emergence of synthetic biologists outside traditional
      research environments, the so called 'do-it-yourself' or 'garage biologists'.
      This paper untangles some of the complexities in the current state of synthetic
      biology and addresses the prospects for dual-use education for practitioners. It
      provides a short overview of the field and discusses identified dual-use issues.
      There follows a discussion of UK networks in synthetic biology, including their
      engagement with ethical, legal, social and dual-use issues and limited
      educational efforts in relation to these. It concludes by outlining options for
      developing a more systematic dual-use education strategy for synthetic biology.

PMID- 22606758
TI  - Research infrastructures, policies and the 'web of prevention': the ethical
      implications of inadequate research environments.
AB  - The dual-use potential of scientific research refers to the possibility that any
      beneficial scientific research may be misused for nefarious purposes by a third
      party. This potential within the life sciences has led to much discussion
      regarding ways to raise awareness and limit possible harm. The concept of a 'web
      of prevention' as a multifaceted system for addressing this potential for harm
      provides a comprehensive method of conceptualizing a system of controls in the
      life sciences. The web of prevention involves multiple stakeholders, from diverse
      backgrounds such as science, public health, security studies and governance.
      Research within the life sciences relies on a number of different structures,
      such as waste disposal and border controls, which provide a comprehensive
      environment for scientists to work in. The web of prevention relies on the
      assumption of these systems working to support any further initiatives that are
      proposed. Unfortunately, in many countries around the world, these systems are
      insufficiently addressed, which may raise ethical problems. Structural problems
      may undermine the web of prevention and alter the responsibilities attributed to
      the individual scientist within this system. Examples from sub-Saharan Africa
      illustrate two pertinent structural difficulties, and these are discussed in
      relation to ethical responsibilities.

PMID- 22606759
TI  - Lessons learned from implementing education on dual-use in Austria, Italy,
      Pakistan and Sweden.
AB  - This paper provides insights into the achievements and challenges of implementing
      education on dual-use in four countries: Austria, Italy, Pakistan and Sweden. It
      draws attention to the different institutional mechanisms through which dual-use
      education may be introduced into academic curricula and some of the difficulties
      encountered in this process. It concludes that there is no 'one size fits all'
      approach to the implementation of dual-use education. Rather, initiatives must be
      tailored to suit the teaching traditions, geographical and historical context in
      which they are being delivered. However, a number of common principles and themes
      can be derived from all four cases. All these courses bring together a number of
      different topics that place 'dual-use' in the broader context of biosafety,
      biosecurity, ethics, law and the environment. The case studies suggest that
      success in this area depends largely on the leadership and commitment of
      individuals directly involved in teaching, who are active within the scientific
      community.

PMID- 22606760
TI  - 'Getting the biosecurity architecture right' in the Asia-Pacific region.
AB  - This paper offers insights to enhance biosecurity in the Asia-Pacific by asking
      three questions. What risks/threats are significant in the region? Which security
      measures should be prioritized? What kind of regional--institutionalized and ad
      hoc--arrangements should be implemented? By doing so the paper specifically
      focuses on two important aspects of biosecurity. Firstly, the issue of immediate
      capacity-building in the context of disaster relief, public health preparedness
      and biodefence. Secondly, the long-term preventive aspect, namely education and
      awareness-raising activities to more broadly promote responsible conduct in life
      science research in terms of laboratory accidents as well as the intentional use
      of biological agents for hostile purposes. In order to promote both aspects of
      biosecurity within the policy process, the paper analyses the strategic value of
      the US-Japan partnership in its efforts to build a biosecurity architecture in
      the Asia-Pacific region.

PMID- 22606761
TI  - Online applied dual-use biosecurity education: a case study from the University
      of Bradford.
AB  - Reflecting a consensus that emerged at the 2008 Meeting of States Parties of the
      Biological Weapons Convention on the importance of ensuring that those working in
      the biological sciences are aware of their obligations under the Convention and
      relevant national legislation and guidelines; and in regard to the consensus on
      the importance of awareness raising and education and training programmes, and of
      the role that these can play in assisting in the implementation of the
      Convention, this paper highlights how novel online e-learning approaches can
      efficiently and effectively be deployed in building a sustainable worldwide
      capability in this much neglected area of education and training. It provides
      examples of the development and evolution of education and training resources,
      notes the importance of standing agenda items for the intersessional process of
      the BWC between the Seventh and Eight Review Conferences and the range of
      opportunities that therefore arise for States Party and civil society
      collaboration in building capacity and achieving sustainability in this area.

PMID- 22606762
TI  - Towards the responsible conduct of scientific research: is ethics education
      enough?
AB  - Much of the discourse on 'beyond the laboratory door' biosecurity to date has
      focused on the need to raise awareness among the scientific community of the
      risks posed by the rapid advancement of biotechnology in recent decades. While
      education is undoubtedly important, a growing body of evidence suggests that
      ethics education does not necessarily translate into ethical behaviour. This
      trend has already been reported in clinical settings, where research has
      highlighted doctors' own reports of ethically dubious practices and challenges
      when confronted with moral dilemmas in their everyday work. The purpose of this
      paper is to critically evaluate the practical value of ethics education and show
      why it is an essential, although insufficient, measure for promoting a culture of
      responsible conduct of research. We conclude by highlighting the importance of
      continuing professional development as a way of maintaining life scientists'
      engagement with biosecurity issues and supporting them in active roles in the
      effective implementation of the Biological and Toxin Weapons Convention (BWC).

PMID- 22606763
TI  - Looking at the formulation of national biosecurity education action plans.
AB  - In order for states to be assured of their compliance with the requirements of
      the Biological and Toxin Weapons Convention, it is necessary that all those
      science and policy stakeholders working within that state should be aware of
      their responsibilities under the Convention. This can only be achieved through a
      comprehensive national biosecurity education programme. We propose that each
      state should produce a national biosecurity action plan, with accompanying
      resources and materials to achieve this. A number of resources are already
      available online to support states in this challenge. We present a model for a
      national biosecurity action plan and propose a number of ways in which this may
      be achieved.

PMID- 22606764
TI  - Preventing the hostile use of the life sciences and biotechnologies; fostering a
      culture of biosecurity and dual use awareness. Conclusions.

PMID- 22606765
TI  - [Do we need to entice young people to the nursing profession? ].

PMID- 22606766
TI  - [I want continuing professional development to be an opportunity for
      professionals. Interview by Yasmina Ouharzoune].

PMID- 22606767
TI  - [Report on end of life conditions in France].

PMID- 22606768
TI  - [Free access to contraception for minors].

PMID- 22606769
TI  - [National investigation on the prevalence of nosocomial infections].

PMID- 22606770
TI  - [The culture of Gypsy travellers in France].
AB  - There are high numbers of travellers, Manush, Gypsy and Roma people in France,
      with secular traditions, an orally-transmitted culture and a community-based way
      of living. Knowing who they are and their culture is essential for all caregivers
      having to provide care to a member of the travelling community.

PMID- 22606771
TI  - [Health depends on quality of life].
AB  - Social-economic conditions, access to care and prevention are important
      indicators of a population's health status. These factors partly explain the
      level of health and the low life expectancy of travelling people. By taking into
      account the difference in lifestyle and the material and psychological conditions
      of travellers, areas to explore for improving the provision of care can be
      envisaged.

PMID- 22606772
TI  - [Caring in a community].
AB  - When travelling people and caregivers encounter each other, they frequently come
      up against difficulties in understanding each other. Romani people do not
      perceive the individual as being separate from the community. Naming the disease
      is difficult, and the future, and thus prevention, is difficult to envisage. An
      insight into their culture, their living conditions and their relationship with
      illness.

PMID- 22606773
TI  - [Communication as a remedy to conflict in the emergency department].
AB  - The encounter between nurses and travelling people sometimes results in
      incomprehension and misunderstandings. To remedy this, the team of the social
      centre in Angouleme has set up meetings between hospital staff and travelling
      people. Rules are defined on both sides enabling each party to feel understood
      and reassured that their needs are respected.

PMID- 22606774
TI  - [Death and mourning in Romani communities].
AB  - It is customary for Romani people to die surrounded by their family and community
      watching over them. The whole family gathers around the deceased for a wake which
      lasts as long as necessary. That is why when one of their community members dies
      in hospital, it is very difficult for the group to accept.

PMID- 22606775
TI  - [Expressing her creativity as a pediatric nurse].

PMID- 22606776
TI  - [Reacting to an act of violence].
AB  - Assaulting a health professional in their workplace has, since 2003, been defined
      in law as an aggravating circumstance. Since the creation of the National
      Observatory on Violence in Hospitals in 2005, all assaults in hospital must be
      recorded. They are classified according to their level of severity. Caregivers
      are obliged to declare to their line manager any act of violence to which they
      have been subjected.

PMID- 22606777
TI  - [Understanding disability, a first act of care].
AB  - One of the ways of taking care of another person consists in banishing
      prejudices. With disabled patients, nurses must avoid empathy which would lead
      them to consider the disability from their personal point of view. Disability
      obliges caregivers to move away from their usual understanding of the body,
      sensations, perceptions and imagination. Rather than putting oneself in the place
      of the disabled person it is a question of understanding the difference.

PMID- 22606778
TI  - [A network of oncologists develop procedures for outpatient chemotherapy].
AB  - In 2007, a network of health professionals in Loire-Atlantique put in place
      procedures for administering chemotherapy treatment at home in which the nurse
      plays a central role, in particular concerning coordination.

PMID- 22606779
TI  - [Caregivers in the face of death].
AB  - Confronted more and more often with the end of life in hospital, caregivers
      approach the death of patients according to their own history and subjectivity.
      Emotions and practices must be brought together in a multi-disciplinary manner
      within nursing teams in order to facilitate the care and support of patients.

PMID- 22606780
TI  - [A fun tool for educating patients with heart failure].
AB  - Therapeutic education is an integral part of the care provided to patients with
      heart failure. It encourages patients to think about their knowledge, as well as
      their behaviour in the face of given symptoms. At Wissembourg hospital in Alsace,
      the design and creation of an informative and fun assessment tool has helped to
      maximise patients' understanding.

PMID- 22606781
TI  - Sophie administers morning medication.

PMID- 22606782
TI  - [Nursing care of the adult patient with an asthmatic crisis].

PMID- 22606783
TI  - [Relational care].

PMID- 22606784
TI  - [A day in the oncology department].

PMID- 22606785
TI  - [Arteriovenous fistula].

PMID- 22606786
TI  - Is your workplace working for you?

PMID- 22606787
TI  - Change in flight plan.

PMID- 22606788
TI  - Gender and TB: illness narratives.

PMID- 22606789
TI  - A commitment to improving employee health.

PMID- 22606790
TI  - Guelph general hospital's HHHRQT.

PMID- 22606791
TI  - Adding insult to injury.

PMID- 22606793
TI  - Linked by blood.

PMID- 22606792
TI  - Hospital noise.

PMID- 22606794
TI  - Community connections.

PMID- 22606795
TI  - How work environment metrics can improve health-care performance.

PMID- 22606796
TI  - Fate of codling moth (Lepidoptera: Tortricidae) in harvested apples held under
      short photoperiod.
AB  - Codling moth, Cydia pomonella L., is a cosmopolitan pest of pome and stone
      fruits. It has been identified as a quarantine pest of concern in a number of
      countries where it is not known to occur, most of them tropical or subtropical
      countries. Although considerable work has been done on the basic biology and
      physiology of this temperate pest, little is known on its potential to develop
      and establish in tropical environments with short photoperiods and few to no days
      below 10 degrees C. Apples were harvested over three field seasons (2007-2009)
      from unmanaged orchards in central Washington State and subjected to simulated
      commercial cold storage at 1.1 +/- 2 degrees C for up to 119 d. After cold
      storage, infested fruits were held at 20 degrees C under a 12:12 L:D photoperiod
      for up to 6 mo. Over the entire experiment only 27% of the larvae collected
      exited the fruit and cocooned. Of those 27%, only 1.06% of larvae held under a
      12:12 L:D photoperiod successfully emerged as moths. No moths emerged when host
      fruit would be available in a representative importing country in the tropics
      over the 3 yr of testing. These results indicate that codling moth in apples from
      the Pacific Northwest pose little threat of surviving and establishing in
      tropical regions where daylength is insufficient to break diapause and the
      chilling requirement is not met.

PMID- 22606797
TI  - Treatment with synthetic brood pheromone (SuperBoost) enhances honey production
      and improves overwintering survival of package honey bee (Hymenoptera: Apidae)
      colonies.
AB  - We evaluated a year-long treatment regime testing synthetic, 10-component, honey
      bee, Apis mellifera L. (Hymenoptera: Apidae), brood pheromone (SuperBoost;
      Contech Enterprises Inc., Delta, BC, Canada) on the productivity and vigor of
      package bee colonies in the lower Fraser Valley of British Columbia, Canada.
      Fifty-eight newlyestablished 1.3-kg (3-lb) colonies treated three times with
      SuperBoost at 5-wk intervals starting 30 April 2009 were compared with 52
      untreated control colonies. Treated colonies produced 84.3% more honey than
      untreated control colonies. By 8 September 2009, SuperBoost-treated colonies had
      35.4% more adults than untreated colonies. By 28 September, net survival of
      treated and control colonies was 72.4 and 67.3%, respectively. On 5 October,
      treated and control colonies were divided into two additional groups, making up
      four cohorts: SuperBoost-treated colonies treated again during fall and spring
      build-up feeding with pollen substitute diet (BeePro, Mann Lake Ltd., Hackensack,
      MN; TIT); controls that remained untreated throughout the year (CCC); colonies
      treated with SuperBoost in spring-summer 2009 but not treated thereafter (TCC);
      and original control colonies treated with SuperBoost during the fall and spring
      build-up feeding periods (CTT). There was no difference among cohorts in
      consumption of BeePro during fall feeding, but TTT colonies (including daughter
      colonies split off from parent colonies) consumed 50.8% more diet than CCC
      colonies during spring build-up feeding. By 21 April, the normalized percentages
      of the original number of colonies remaining (dead colonies partially offset by
      splits) were as follows: CCC, 31.4%; CTT, 43.8%; TCC, 53.59%; and TTT, 80.0%. The
      net benefit of placing 100 newly established package bee colonies on a year-long
      six-treatment regime with SuperBoost would be US$6,202 (US$62.02 per colony). We
      conclude that treatment with SuperBoost enhanced the productivity and survival of
      package bee colonies and hypothesize that similar results could be achieved with
      established colonies.

PMID- 22606798
TI  - Functionality of Varroa-resistant honey bees (Hymenoptera: Apidae) when used in
      migratory beekeeping for crop pollination.
AB  - Two types of honey bees, Apis mellifera L. (Hymenoptera: Apidae), bred for
      resistance to Varroa destructor Anderson & Trueman were evaluated for performance
      when used in migratory crop pollination. Colonies of Russian honey bees (RHB) and
      outcrossed bees with Varroa-sensitive hygiene (VSH) were managed without miticide
      treatments and compared with colonies of Italian honey bees that served as
      controls. Control colonies were managed as groups which either were treated twice
      each year against V. destructor (CT) or kept untreated (CU). Totals of 240 and
      247 colonies were established initially for trials in 2008 and 2009,
      respectively. RHB and VSH colonies generally had adult and brood populations
      similar to those of the standard CT group regarding pollination requirements. For
      pollination of almonds [Prunus dulcis (Mill.) D.A.Webb] in February, percentages
      of colonies meeting the required six or more frames of adult bees were 57% (VSH),
      56% (CT), 39% (RHB), and 34% (CU). RHB are known to have small colonies in early
      spring, but this can be overcome with appropriate feeding. For later pollination
      requirements in May to July, 94-100% of colonies in the four groups met
      pollination size requirements for apples (Malus domestica Borkh.), cranberries
      (Vaccinium macrocarpon Aiton), and lowbush blueberries (Vaccinium angustifolium
      Aiton). Infestations with V. destructor usually were lowest in CT colonies and
      tended to be lower in VSH colonies than in RHB and CU colonies. This study
      demonstrates that bees with the VSH trait and pure RHB offer alternatives for
      beekeepers to use for commercial crop pollination while reducing reliance on
      miticides. The high frequency of queen loss (only approximately one fourth of
      original queens survived each year) suggests that frequent requeening is
      necessary to maintain desired genetics.

PMID- 22606799
TI  - Population dynamics of Cacopsylla melanoneura (Hemiptera: Psyllidae) in northeast
      Italy and its role in the apple proliferation epidemiology in apple orchards.
AB  - In the current study, incidence of 'Candidatus Phytoplasma mali' in an
      experimental apple orchard in northeast Italy, in addition to abundance and
      phytoplasma infectivity of Cacopsylla melanoneura (Forster) (Hemiptera:
      Psyllidae) was determined and the role of this psyllid as a vector of 'Ca. P.
      mali' in this region was reviewed. Insect samples collected in the orchard by the
      beating method indicated high abundance of C. melanoneura (up to 7.92
      specimens/branch); however, the psyllid C. picta was not observed. Molecular
      analyses revealed presence of 'Ca. P. mali' in 6.25% of overwintered psyllids.
      This infection rate is quite high in comparison to other localities where C.
      melanoneura is known as the main vector of the phytoplasma. This finding supports
      the assumption that C. melanoneura also is paramount in the epidemiology of the
      apple proliferation disease also in northeast Italy. Moreover, we correlated
      immigration dynamics to the temperatures registered in the apple orchard, and
      defined an immigration index to predict the progressive arrival of the
      overwintered adults from winter sites. Psyllids start to reach the apple orchards
      when either the average of the maximum temperature of the 7 d is above 9.5
      degrees C or the immigration index has a positive value. This index will be a
      useful tool for the growers to prevent apple proliferation phytoplasma spread
      with well-timed insecticide treatments targeted against C. melanoneura. However,
      further research is needed to validate or adjust the index to other apple growing
      regions, which may affect more efficacious management of this disease and psyllid
      vector.

PMID- 22606800
TI  - Weedy hosts and prevalence of potential leafhopper vectors (Hemiptera:
      Cicadellidae) of a phytoplasma (16SrIX group) associated with Huanglongbing
      symptoms in citrus groves.
AB  - Huanglongbing (HLB) is a severe citrus (Citrus spp.) disease associated with the
      bacteria genus Candidatus Liberibacter, detected in Brazil in 2004. Another
      bacterium was found in association with HLB symptoms and characterized as a
      phytoplasma belonging to the 16SrIX group. The objectives of this study were to
      identify potential leafhopper vectors of the HLB-associated phytoplasma and their
      host plants. Leafhoppers were sampled every other week for 12 mo with sticky
      yellow cards placed at two heights (0.3 and 1.5 m) in the citrus tree canopy and
      by using a sweep net in the ground vegetation of two sweet orange, Citrus
      sinensis (L.) Osbeck, groves infected by the HLB-phytoplasma in Sao Paulo state.
      Faunistic analyses indicated one Agalliinae (Agallia albidula Uhler) and three
      Deltocephalinae [Balclutha hebe (Kirkaldy), Planicephalus flavicosta (Stal), and
      Scaphytopius (Convelinus) marginelineatus (Stal)] species, as the most abundant
      and frequent leafhoppers (Hemiptera: Cicadellidae). Visual observations indicated
      an association of leafhopper species with some weeds and the influence of weed
      species composition on leafhopper abundance in low-lying vegetation. S.
      marginelineatus and P. flavicosta were more frequent on Sida rhombifolia L. and
      Althernantera tenella Colla, respectively, whereas A. albidula was observed more
      often on Conyza bonariensis (L.) Cronq. and B. hebe only occurred on grasses. DNA
      samples of field-collected S. marginelineatus were positive by polymerase chain
      reaction and sequencing tests for the presence of the HLB-phytoplasma group,
      indicating it as a potential vector. The association of leafhoppers with their
      hosts may be used in deciding which management strategies to adopt against weeds
      and diseases in citrus orchards.

PMID- 22606801
TI  - Life table of Tamarixia radiata (Hymenoptera: Eulophidae) on Diaphorina citri
      (Hemiptera: Psyllidae) at different temperatures.
AB  - Tamarixia radiata (Waterston, 1922) is the main parasitoid of Diaphorina citri
      (Kuwayama, 1907), and has been used in classical biological control programs in
      several countries. The current study investigated the biology and determined the
      fertility life table of T. radiata in different temperatures, to obtain
      information to support the establishment of a biological control program for D.
      citri in Brazil. Fifth-instar nymphs of D. citri were offered to females of T.
      radiata for parasitism, for 24 h. Then, the parasitoid was removed and the nymphs
      were placed in incubators at 15, 20, 25, 30, or 35 +/- 1 degrees C, 70 +/- 10%
      RH, and a 14-h photophase. The percentages of parasitism and emergence, the sex
      ratio, and the preimaginal period of T. radiata were determined. The fertility
      life table was developed from the biological data. The highest parasitism rate
      (77.24%) was obtained at a temperature of 26.3 degrees C, and the lowest
      parasitism rates occurred at 15 and 35 degrees C (23.1 and 40.2%, respectively).
      The highest percentages of emergence of the parasitoid occurred at 25, 30, and 35
      degrees C (86.7, 88.3, and 78.8%, respectively), with the calculated peak at 30.8
      degrees C (89.90%). The duration of the preimaginal developmental period for both
      females and males of T. radiata was inversely proportional to temperature in the
      thermal range of 15-35 degrees C. The development of T. radiata occurred at all
      temperatures studied, and the highest viability of the preimaginal period
      occurred at 25 degrees C. The highest values of net reproductive rate and finite
      growth ratio (lambda) were observed at 25 degrees C, so that in each generation
      the population of T. radiata increased 126.79 times, higher than the values
      obtained at the other temperatures.

PMID- 22606802
TI  - Field testing Chinese and Japanese gypsy moth nucleopolyhedrovirus and
      disparvirus against a Chinese population of Lymantria dispar asiatica in Huhhot,
      Inner Mongolia, People's Republic of China.
AB  - The activity of three geographic isolates of the gypsy moth nucleopolyhedrovirus
      (LdMNPV) was evaluated in field trials against larvae of the Chinese population
      of Lymantria dispar asiatica Vnukovskij in Inner Mongolia, People's Republic of
      China, in 2004, 2005, and 2006. Although the Chinese isolate of the virus, LdMNPV
      H, was the most pathogenic of the isolates tested, having the lowest mean lethal
      concentration causing 50% and 95% larval mortality, the increase in efficacy that
      would be obtained by incorporating this isolate into a commercial product does
      not justify the time or expense required to register it for use in the United
      States or Canada. The commercially available North American isolate, LdMNPV-D,
      was moderately pathogenic, whereas the Japanese isolate, LdMNPV-J, was the least
      pathogenic. The slopes of the dose-response regression lines for the three virus
      isolates indicated that the Chinese gypsy moth larvae were more homogenously
      susceptible to LdMNPV-H and LdMNPV-D than to LdMNPV-J. Time-response data showed
      that LdMNPV-J was significantly more virulent, but at a much higher dose, than
      the other two isolates, causing 50% mortality in the shortest time, followed by
      LdMNPV-H and LdMNPV-D. Rainfall immediately after the application of LdMNPV-D in
      2005 resulted in significantly reduced gypsy moth larval mortality.

PMID- 22606803
TI  - Effect of insecticides and Plutella xylostella (Lepidoptera: Plutellidae)
      genotype on a predator and parasitoid and implications for the evolution of
      insecticide resistance.
AB  - In the laboratory and in cages in the greenhouse, we evaluated the toxicity of
      two insecticides (lambda-cyhalothrin and spinosad) on the parasitoid, Diadegma
      insulare (Cresson), and the predator, Coleomegilla maculate (DeGeer), both
      natural enemies of the diamondback moth, Plutella xylostella (L.). Lambda
      cyhalothrin was very toxic to both natural enemies. Spinosad was less toxic to C.
      maculata adults and larvae, and slightly toxic to D. insulare. Both natural
      enemies suppressed P. xylostella populations in cages with 80% spinosad-treated
      and 20% nontreated plants; such suppression was not seen when lambda-cyhalothrin
      was used. Using broccoli, Brassica oleracea L. variety italica, a common host for
      P. xylostella, we also studied direct and indirect effects of both natural
      enemies in the presence and absence of the two insecticides and to different P.
      xylostella genotypes: resistant to the insecticide, susceptible, or heterozygous.
      Neither natural enemy could distinguish host genotype if P. xylostella were
      feeding on nontreated plants. They could also not distinguish between larvae
      feeding on spinosad-treated plants and nontreated plants, but D. insulare could
      distinguish between larvae feeding on lambda-cyhalothrin treated and nontreated
      plants. Our studies suggest that lambda-cyhalothrin has direct toxicity to these
      two natural enemies, can affect their host foraging and acceptance of P.
      xylostella and consequently would not be compatible in conserving these natural
      enemies in a program for suppression of P. xylostella. In contrast, our studies
      suggest that treatment with spinosad has much less effect on these natural
      enemies and would allow them to help suppress populations of P. xylostella. These
      findings are discussed in relation to the evolution of insecticide resistance and
      suppression of the pest populations.

PMID- 22606804
TI  - Host status of Meyer and Eureka lemons for Anastrepha ludens.
AB  - Host status for Mexican fruit fly (Anastrepha ludens (Loew)) was examined under
      laboratory conditions in cage infested Eureka and Meyer lemons. Our approach was
      to allow females to oviposit on the two cultivars in separate laboratory cages
      with aluminum foil covering to restrict the areas where females had access to
      fruit surface. Fruit of each cultivar were placed in covered trays for
      incubations and at approximately weekly intervals, fruit were removed, dissected,
      and live and dead eggs and larvae tabulated in each tissue of the fruit.
      Infestation and survival were tabulated and analyzed for the effects of harvest
      date, fruit color and brix indices, postoviposition period, and cultivar.
      Infestation rate, determined by counts of total eggs and larvae was significantly
      higher in Meyer lemons. In both cultivars, females deposited eggs into both
      albedo and pulp tissue but not into flavedo. Both cultivars showed high
      resistance (> 90% mortality) to egg and first instars survival in albedo and
      pulp. Second and third instars surviving in the pulp had high survival rates (>
      60%) in both cultivars in fruit dissected at weeks 2-4 after infestation. Total
      adults produced were slightly higher, and total second and third stage larvae
      were also higher for Meyer lemons. Numbers of adults and total second and third
      stage larvae increased in Eureka lemons in more mature fruit, but the higher
      numbers in Meyer lemons were not associated with fruit maturity, at time of
      infestation. Numbers of second and third stage larvae were significantly
      correlated with some fruit color indices in Eureka but not in Meyer lemons.
      Application of these results to quarantine risk analysis is discussed.

PMID- 22606805
TI  - Exceptional longevity in the tephritid, Ceratitis rosa, a close relative of the
      Mediterranean fruit fly.
AB  - This study shows that the fruit fly, Ceratitis rosa (Karsch), has a significantly
      longer life span than the medfly, C. capitata (Wiedemann); the species used as a
      model organism for the demographics of insect aging. This was somewhat surprising
      given that both have similar distributions and overlapping niches. We postulate
      that the greater longevity of C. rosa is related to the fact that it can occupy
      colder habitats where the availability of suitable host plants may be very
      unpredictable in both time and space.

PMID- 22606806
TI  - Using black soldier fly larvae for processing organic leachates.
AB  - A large number of biodegradable byproducts including alcohols, soluble
      saccharides, volatile organic acids, and amines accumulate in the liquid fraction
      (leachate) produced as vegetal and food scrap waste decomposes. Untreated
      leachate, because it is rich in nutrients and organic byproducts, has a high
      chemical oxygen demand and is normally cleared of soluble organic byproducts by
      mineralization before its discharge into waterways. Mineralizing leachates using
      chemical and microbial biotechnologies is, however, a lengthy and costly process.
      We report here that the larvae of the black soldier fly Hermetia illucens (L.)
      (Diptera: Stratiomyidae), an insect rich in protein and lipids, and having
      significant commercial value, while feeding and growing off of compost leachate,
      lowers its chemical oxygen demand relative to that of leachate unexposed to
      larvae, neutralizes its acidity, and clears it of volatile organic acids, amines,
      and alcohols. These observations demonstrate that black soldier fly larvae could
      be used to help offset the cost and clean up of organic solutes in leachate waste
      streams while recycling carbon, nitrogen, and phosphate into usable and
      commercially valuable biomass.

PMID- 22606807
TI  - Repellent effect of santalol from sandalwood oil against Tetranychus urticae
      (Acari: Tetranychidae).
AB  - Thirty-four essential oils were screened for their repellent activities against
      the twospotted spider mite, Tetranychus urticae Koch (Acarina: Tetranychidae), at
      0.1% concentration level using choice and no-choice laboratory bioassays. Of
      these, 20 essential oils showed significant repellencies against T. urticae in
      the choice tests. In subsequent no-choice tests using these 20 essential oils,
      only sandalwood oil showed significant repellency against T. urticae. Total
      number of eggs oviposited by T. urticae was significantly lower than controls in
      the choice tests when the kidney bean leaves were treated with 1 of 14 essential
      oils. The significant repellency of sandalwood oil against T. urticae lasted at
      least for 5 h at the 0.1% concentration level. Our GC-MS analysis indicated that
      the major components of the sandalwood oil were alpha-santalol (45.8%), beta
      santalol (20.6%), beta-sinensal (9.4%), and epi-beta-santalol (3.3%). Santanol, a
      mixture of the two main components in the sandalwood oil, appears to be
      responsible for the repellency of sandalwood oil against T. urticae.

PMID- 22606808
TI  - Pseudacteon tricuspis: its behavior and development according to the social form
      of its host and the role of interference competition among females.
AB  - We studied how the behavior and performance of Pseudacteon tricuspis Borgmeier
      varies with the social form of its host Solenopsis invicta Buren, in its native
      range in Argentina where monogyne colonies are more abundant than polygynes
      (approximately 75 vs. 25%). Female, P. tricuspis took 44% less time (50 vs. 89 s)
      to attack monogyne than polygyne ants, but oviposition attempts were similar (23
      vs. 18 attacks). The presence of the parasitoid affected the average size of
      foragers on the trail, with the proportion of minor workers increasing on both
      social forms. In the laboratory, P. tricuspis selected similar host sizes,
      although pupal survival was 25% higher on monogynes than on polygynes.
      Developmental times of both genders were similar (33-35 d), although larger
      females emerged from bigger hosts. The sex ratio of P. tricuspis was more male
      biased when exploiting polygyne ants. Intraspecific competition significantly
      affected parasitoid reproductive success, being significantly higher for a
      solitary female than when three females were present, although the size of
      workers selected did not vary. The male:female ratio also changed, being 1:1
      without competition but 2:1 with competition. We demonstrated for the first time
      the consequences of interference competition among P. tricuspis females, a common
      behavior observed in others parasitoids. We discuss why P. tricuspis sex ratios
      are always biased toward males in both social forms and suggest that similar
      studies of interference competition within and between already naturalized
      Pseudacteon species in the United States could help predict establishment
      patterns.

PMID- 22606809
TI  - Efficacy of Fluon conditioning for capturing cerambycid beetles in different trap
      designs and persistence on panel traps over time.
AB  - Fluon PTFE is a fluoropolymer dispersion applied as a surface conditioner to
      cross-vane panel traps to enhance trap efficiency for cerambycid beetles. We
      describe the results of three experiments to further optimize cerambycid traps of
      different designs and to test the effect of Fluon over time. We tested Fluon with
      Lindgren funnel and panel traps fitted with either wet or dry collection cups on
      catches of cerambycid beetles and how the effect of Fluon on panel traps
      persisted. Fluon-treated funnel traps with wet collection cups captured
      approximately 6x more beetles than the untreated funnel traps with wet collection
      cups. Untreated funnel traps with dry collection cups did not capture any
      beetles; however, Fluon-treated funnel traps with dry collection cups captured an
      average of four beetles per trap. Fluon-treated panel traps with wet collection
      cups captured approximately 9x more beetles than untreated panel traps with wet
      collection cups. Fluon-treated panel traps with dry collection cups captured
      approximately 11x more beetles than untreated panel traps with dry collection
      cups. The effect of Fluon on capturing cerambycid beetles did not decline after
      use in one or two field seasons. There was no significant difference in the
      number of beetles captured in freshly treated panel traps compared with traps
      that had been used for 1 or 2 yr. Fluon-treated traps captured nine species that
      were not captured in untreated traps. Conditioning both Lindgren funnel and panel
      traps with Fluon enhances the efficacy and sensitivity of traps deployed to
      detect exotic cerambycid species, or for monitoring threatened species at low
      population densities.

PMID- 22606810
TI  - Surveys for Stenoma catenifer (Lepidoptera: Elachistidae) and associated
      parasitoids infesting avocados in Peru.
AB  - Surveys for Stenoma catenifer Walsingham, the avocado seed moth, and its
      associated larval parasitoids were conducted in the Departments of Junin,
      Huanuco, Cusco, and Madre de Dios in Peru. Fruit infestation levels in some areas
      ranged from 0 to 58%, and parasitism of S. catenifer larvae in Junin and Huanuco
      was 23%. Five species of hymenopteran parasitoid in two families, Braconidae
      (Apanteles sp., Hypomicrogaster sp., and Chelonus sp.) and Ichneumonidae
      (Pristeromerus sp. and Xiphosomella sp.), were reared from larvae, and one
      species of tachinid fly (Chrysodoria sp.) emerged from pupae. The dominant larval
      parasitoid, a gregarious Apanteles sp., accounted for 55% of parasitized hosts.
      Branch and twig tunneling by S. catenifer larvae in a commercial Hass avocado
      orchard was observed in Cusco. The field attractiveness of the sex pheromone of
      S. catenifer was demonstrated with 73% of monitoring traps deployed in three
      departments (Junin, Huanuco, and Cusco) catching male moths. Approximately 55% of
      avocado fruit sourced from the Province of Chanchamayo (Junin) and purchased at
      the Mercado Modelo de Frutas in La Victoria, in central Lima were infested with
      larvae of S. catenifer. Infested avocado fruit sold at this market could
      represent a potential incursion threat to coastal Hass avocado production regions
      in Peru that are reportedly free of this pest.

PMID- 22606811
TI  - Effects of a naturally occurring and a synthetic synergist on toxicity of three
      insecticides and a phytochemical to navel orangeworm (Lepidoptera: Pyralidae).
AB  - The navel orangeworm, Amyelois transitella (Walker) (Lepidoptera: Pyralidae), is
      the most destructive lepidopteran pest of almonds [Prunus dulcis (Mill.)
      D.A.Webb] and pistachios (Pistacia vera L.) in California and is a serious
      problem in figs (Ficus carica L.) and walnuts (Juglans spp.). In addition to
      direct damage, larval feeding leaves nuts vulnerable to infection by Aspergillus
      spp., fungi that produce toxic aflatoxins. A potentially safe and sustainable
      approach for managing navel orangeworm in orchards may be to use natural
      essential oil synergists to interfere with this insect's ability to detoxify
      insecticides and phytochemicals. We tested the effects of a naturally occurring
      plant-derived chemical, myristicin, and a synthetic inhibitor of cytochrome P450
      monooxygenases (P450s), piperonyl butoxide, on the toxicity of three insecticides
      (alpha-cypermethrin, tau-fluvalinate, and methoxyfenozide [Intrepid]) and a
      phytochemical (xanthotoxin) to A. transitella. Piperonyl butoxide significantly
      synergized alpha-cypermethrin and tau-fluvalinate, whereas myristicin synergized
      only alpha-cypermethrin. Piperonyl butoxide synergized the toxicity of
      xanthotoxin as early as 72 h after exposure, whereas myristicin synergized
      xanthotoxin after 120 h. In view of these findings and the limited availability
      of environmentally safe synthetic insecticides for sustainable management,
      particularly in organic orchards, myristicin is a potential field treatment in
      combination with insecticides to reduce both navel orangeworm survival and
      aflatoxin contamination of nuts. In addition, this study demonstrates that in A.
      transitella the insect growth regulator methoxyfenozide is not detoxified by
      P450s.

PMID- 22606812
TI  - Genetic characterization of fall armyworm (Lepidoptera: Noctuidae) host strains
      in Argentina.
AB  - Fall armyworm is a major economic pest throughout the Western Hemisphere.
      Previous studies of populations in the southern United States, Brazil, and the
      Caribbean demonstrated the existence of two morphologically identical but
      genetically distinct host strains that can only be distinguished using genetic
      markers, including polymorphisms in the mitochondrial Cytochrome Oxidase I (COI)
      gene and in the Z-chromosome linked Triose phosphate isomerase (Tpi) gene. The
      strains differ in some physiological and behavioral characteristics, most notably
      their preference for different plant hosts, but are capable of hybridizing in the
      laboratory and in the field. These traits suggest that the strains are in the
      process of divergence, which may or may not be hemispheric in scope. The
      objective of this study was to determine whether the two strains are present in
      Argentina. It was found that the strain-diagnostic haplotypes of the COI and Tpi
      genes subdivided the Argentina population into two major groups. Each group
      displayed biases in their distribution among different host plants that were
      generally consistent with expected strain behavior. The overall results indicated
      that Argentina fall armyworm exhibit similar genetics and behavior to populations
      in the rest of the hemisphere. In addition, the Argentina populations had
      comparable haplotype frequencies to those from Brazil and Texas, consistent with
      possible interactions with these fall armyworm groups, but appeared to have had
      minimal exchanges with those from Puerto Rico or Florida.

PMID- 22606813
TI  - Influence of trap color and host volatiles on capture of the emerald ash borer
      (Coleoptera: Buprestidae).
AB  - Field trapping assays were conducted in 2009 and 2010 throughout western
      Michigan, to evaluate lures for adult emerald ash borer, A. planipennis Fairmaire
      (Coleoptera: Buprestidae). Several ash tree volatiles were tested on purple prism
      traps in 2009, and a dark green prism trap in 2010. In 2009, six bark oil
      distillate lure treatments were tested against manuka oil lures (used in 2008 by
      USDA APHIS PPQ emerald ash borer cooperative program). Purple traps baited with
      80/20 (manuka/phoebe oil) significantly increased beetle catch compared with
      traps baited with manuka oil alone. In 2010 we monitored emerald ash borer
      attraction to dark green traps baited with six lure combinations of 80/20
      (manuka/phoebe), manuka oil, and (3Z)-hexenol. Traps baited with manuka oil and
      (3Z)-hexenol caught significantly more male and total count insects than traps
      baited with manuka oil alone. Traps baited with manuka oil and (3Z)-hexenol did
      not catch more beetles when compared with traps baited with (3Z)-hexenol alone.
      When compared with unbaited green traps our results show that (3Z)-hexenol
      improved male catch significantly in only one of three field experiments using
      dark green traps. Dark green traps caught a high number of A. planipennis when
      unbaited while (3Z)-hexenol was seen to have a minimal (nonsignificant) trap
      catch effect at several different release rates. We hypothesize that the
      previously reported kairomonal attractancy of (3Z)-hexenol (for males) on light
      green traps is not as obvious here because of improved male attractancy to the
      darker green trap.

PMID- 22606814
TI  - Dispersal of invasive forest insects via recreational firewood: a quantitative
      analysis.
AB  - Recreational travel is a recognized vector for the spread of invasive species in
      North America. However, there has been little quantitative analysis of the risks
      posed by such travel and the associated transport of firewood. In this study, we
      analyzed the risk of forest insect spread with firewood and estimated related
      dispersal parameters for application in geographically explicit invasion models.
      Our primary data source was the U.S. National Recreation Reservation Service
      database, which records camper reservations at > 2,500 locations nationwide. For
      > 7 million individual reservations made between 2004 and 2009 (including visits
      from Canada), we calculated the distance between visitor home address and
      campground location. We constructed an empirical dispersal kernel (i.e., the
      probability distribution of the travel distances) from these "origin-destination"
      data, and then fitted the data with various theoretical distributions. We found
      the data to be strongly leptokurtic (fat-tailed) and fairly well fit by the
      unbounded Johnson and lognormal distributions. Most campers ( approximately 53%)
      traveled <100 km, but approximately 10% traveled > 500 km (and as far as 5,500
      km). Additionally, we examined the impact of geographic region, specific
      destinations (major national parks), and specific origin locations (major cities)
      on the shape of the dispersal kernel, and found that mixture distributions (i.e.,
      theoretical distribution functions composed of multiple univariate distributions)
      may fit better in some circumstances. Although only a limited amount of all
      transported firewood is likely to be infested by forest insects, this still
      represents a considerable increase in dispersal potential beyond the insects'
      natural spread capabilities.

PMID- 22606815
TI  - Predicting Dendroctonus pseudotsugae (Coleoptera: Curculionidae) antiaggregation
      pheromone concentrations using an instantaneous puff dispersion model.
AB  - An instantaneous puff dispersion model was used to assess concentration fields of
      the Douglas-fir beetle, Dendroctonus pseudotsugae Hopkins, antiaggregation
      pheromone, 3-methylcyclohex-2-en-1-one (MCH), within a 1-ha circular plot.
      Several combinations of MCH release rate and releaser spacing were modeled to
      theoretically analyze optimal deployment strategies. The combinations of MCH
      release rate and releaser spacing used in the modeling exercise were based on
      results of previous field studies of treatment efficacy. Analyses of model
      results suggest that a release rate up to six times the initial standard, at a
      correspondingly wider spacing to keep the total amount of pheromone dispersed per
      unit area constant, may be effective at preventing Douglas-fir beetle
      infestation. The model outputs also provide a visual representation of pheromone
      dispersion patterns that can occur after deployment of release devices in the
      field. These results will help researchers and practitioners design more
      effective deployment strategies.

PMID- 22606816
TI  - Effect of tree species and end seal on attractiveness and utility of cut bolts to
      the redbay ambrosia beetle and granulate ambrosia beetle (coleoptera:
      Curculionidae: Scolytinae).
AB  - The redbay ambrosia beetle, Xyleborus glabratus Eichhoff, is a non-native
      invasive pest and vector of the fungus that causes laurel wilt disease in certain
      trees of the family Lauraceae. This study assessed the relative attractiveness
      and suitability of cut bolts of several tree species to X. glabratus. In 2009,
      female X. glabratus were equally attracted to traps baited with swampbay (Persea
      palustris (Rafinesque) Sargent) and camphortree (Cinnamomum camphora (L.) J.
      Presl), which were more attractive than avocado (Persea americana Miller),
      lancewood (Ocotea coriacea (Swartz) Britton), and sweetbay (Magnolia virginiana
      L.). These species were more attractive than loblolly bay (Gordonia lasianthus
      (L.) J. Ellis). X. glabratus entrance hole density and emergence from caged bolts
      were highest on swampbay and camphortree. In 2010, swampbay was significantly
      more attractive to X. glabratus than sassafras (Sassafras albidum (Nuttall)
      Nees), yellow poplar (Liriodendron tulipifera L.), and eastern redbud (Cercis
      canadensis L.). Sassafras bolts end sealed with a liquid wax-and-water emulsion
      were more attractive to X. glabratus than end-sealed bolts of yellow poplar and
      redbud. Relative to unsealed bolts, end seal decreased X. glabratus entrance hole
      density on swampbay and decreased granulate ambrosia beetle (Xylosandrus
      crassiusculus (Motschulsky)) trap catch, entrance hole density, and adult
      emergence from swampbay. X. crassiusculus was not attracted to sassafras, yellow
      poplar, and redbud and was not more attracted to manuka oil than to unbaited
      traps. Sassafras was more attractive to X. glabratus than previously reported and
      supported reproducing populations of the insect. End sealing bolts with a wax-and
      water emulsion may not be optimal for attracting and rearing ambrosia beetles in
      small logs.

PMID- 22606817
TI  - Efficacy of wax matrix bait stations for Mediterranean fruit flies (Diptera:
      Tephritidae).
AB  - Tests were conducted that evaluated efficacy of wax matrix bait stations for
      Ceratitis capitata (Wiedemann) adults in Guatemala. Bait stations were exposed to
      outdoor conditions to determine effect of weathering on longevity as indicated by
      bait station age. Results of laboratory tests found that bait stations with
      spinosad and ammonium acetate remained effective for at least 31 d compared with
      pesticide-free controls, although there was some loss of efficacy over time.
      Percentage mortality for bait station strips with 2% spinosad and 1% ammonium
      acetate decreased from 100 +/- 0.0% on day 0 to 70 +/- 7.1% after 31 d. Ammonia
      concentration had little effect on percentage mortality although there was some
      indication that ammonia concentration affected number of flies observed on the
      bait stations. Bait station strips (one per cage) were more effective than
      controls for 6-8 wk when tests were conducted in field cages (3 m diameter x 2
      m), but only 2-3 wk when tests were conducted in large (2.5 m high and 6.0 m wide
      and 7.5 m long) field cages. Longevity was restored when multiple bait stations
      (3, 6, or 12) were deployed per cage. Bait stations containing methomyl were used
      for field tests of efficacy for wild flies. Dipped lure bait stations, which were
      made by coating two edges of commercial ammonium acetate and trimethylamine
      lures, killed six times more flies than corn cob bait stations dipped into a
      Nulure/malathion solution. They also killed more flies than pesticide-free
      controls for 8 wk.

PMID- 22606818
TI  - Effects of southern highbush blueberry cultivar and treatment threshold on flower
      thrips populations.
AB  - In Florida, southern highbush (SHB) blueberries (Vaccinium corymbosum L. x
      Vaccinium darrowi Camp) are grown for a highly profitable early season fresh
      market. Flower thrips are the key pest of SHB blueberries, and Frankliniella
      bispinosa (Morgan) is the most common species found. Flower thrips injure
      blueberry flowers by feeding and ovipositing in all developing tissues. These
      injuries can lead to scarring of developing fruit. The objectives of this study
      were to determine the relationship between thrips and yield in different SHB
      blueberry cultivars and to determine an action threshold. Experiments were
      conducted during early spring 2007 and 2008 on four farms; a research farm in
      Citra, FL; and three commercial farms, two in Hernando Co., FL., and one in Lake
      Co., FL. At the Citra farm, 'Emerald', 'Jewel', 'Millennia', and 'Star'
      blueberries were compared in 2007, and all but Star were compared in 2008. On the
      Hernando and Lake Co. farms, two treatment thresholds (100 and 200 thrips per
      trap) and an untreated control and four cultivars (Emerald, Jewel, Millennia, and
      'Windsor') were compared. Emerald consistently had more thrips per trap and per
      flower than the other cultivars on all four farms. However, this did not always
      lead to an increase in fruit injury. Thrips numbers exceeded the threshold on
      only one farm in 2007, and there was a significantly lower proportion of injured
      and malformed fruit in the 100 thrips per trap threshold treatment compared with
      the control on this farm.

PMID- 22606819
TI  - Risk assessment of selected insecticides on Tamarixia triozae (Hymenoptera:
      Eulophidae), a parasitoid of Bactericera cockerelli (Hemiptera: Trizoidae).
AB  - Tamarixia triozae (Burks) (Hymenoptera: Eulophidae) is an important parasitoid of
      the potato or tomato psyllid, Bactericera cockerelli (Sulc) (Hemiptera:
      Trizoidae), a serious pest of potato (Solanum tuberosum L.), tomato (Solanum
      lycopersicum L.), and other solanaceous vegetables in many countries. To produce
      a marketable crop, insecticides are required when B. cockerelli populations reach
      economically damaging levels. We evaluated 11 commonly used insecticides for
      their effects on T. triozae. Glass-surface residues of spinetoram, imidacloprid
      cyfluthrin, abamectin, and tolfenpyrad caused 100% mortality of T. triozae in 72
      h, and the leaf residue of spinetoram was extremely toxic to T. triozae adults;
      even 15-d-old residues caused 100% mortality. Cyantraniliprole, fenpyroximate,
      pymetrozine, spirotetramat, spiromesifen, and chenopodium oil did not cause
      significant mortality in either glass surface or leaf-residue bioassays.
      Ingestion of spinetoram, abamectin, and imidacloprid+cyfluthrin (Leverage) by the
      adults resulted in 100% mortality in 12 h, and tolfenpyrad, 75.0% mortality in 12
      h; whereas chenopodium oil and pymetrozine showed moderate effects on adult
      survival. Ingestion of abamectin, imidacloprid-cyfluthrin, and spinetoram killed
      all adults in the first day of treatment, whereas female adults in the treatment
      of pymetrozine lived 80.8 d, which was similar to those in the control. Ingestion
      of abamectin, imidacloprid-cyfluthrin, chenopodium oil, and spinetoram killed all
      male adults in the first day, whereas ingestion of other insecticides did not
      cause significant mortality, but reduced percent parasitism. Abamectin,
      imidacloprid-cyfluthrin, and spinetoram had the most deleterious effects on T.
      triozae, and have the least potential for use in integrated control programs
      using this parasitoid.

PMID- 22606820
TI  - Identification of the sex pheromone of the invasive scale Acutaspis albopicta
      (Hemiptera: Diaspididae), arriving in California on shipments of avocados from
      Mexico.
AB  - As a result of relaxation of importation restrictions ordered by the Animal and
      Plant Health Inspection Service of the U.S. Department of Agriculture, shipments
      of fresh avocados from Mexico began entering California year-round in 2007,
      despite the fact that these shipments were heavily infested with a number of
      exotic and potentially invasive armored scale species that are not thought to be
      present in California. Here, we report the identification of the sex pheromone of
      one of these species, Acutaspis albopicta (Cockerell), from a quarantine colony
      of these insects initiated from specimens collected from commercial shipments of
      Mexican avocados. The compound was identified as [(1S,3S)-2,2-dimethyl-3-(prop-1
      en-2-yl)cyclobutyl)]methyl (R)-2-methylbutanoate, and was similar in structure to
      the pheromones of several other scale and mealybug species. In laboratory
      bioassays, the pheromone was highly attractive to male scales in microgram doses.
      The pheromone will provide a very sensitive and selective tool for detection of
      the scale to try and prevent its permanent establishment in California.

PMID- 22606821
TI  - Interactions of light intensity, insecticide concentration, and time on the
      efficacy of systemic insecticides in suppressing populations of the sweetpotato
      whitefly (Hemiptera: Aleyrodidae) and the citrus mealybug (Hemiptera:
      Pseudococcidae).
AB  - The impact of light intensity on the uptake and persistence of the systemic
      neonicotinoid insecticides, imidacloprid and dinotefuran, were evaluated in
      poinsettia (Euphorbia pulcherrima Willd.) and yellow sage (Lantana camara L.).
      Insecticide residues were measured in leaves sampled from the treated plants at
      four time intervals after treatment to determine the relationship between
      insecticide concentration and efficacy against two insect pests: sweetpotato
      whitefly, Bemisia tabaci Gennadius, and the citrus mealybug, Planococcus citri
      Risso. The insecticides were evaluated at their respective label rate and at the
      comparable label rate of the other insecticide under two different light
      environments: ambient and shade. The uptake of dinotefuran into yellow sage was
      more rapid at both treatment rates than both rates of imidacloprid, resulting in
      higher percent mortality of whitefly nymphs (89.8-100) compared with imidacloprid
      (14.1-89.2) across all 4 wk. Additionally, plants that received both rates of
      dinotefuran had fewer whitefly pupae (< 1.0) at week 4 compared with imidacloprid
      treated plants (23.7-25.3). The uptake of dinotefuran into poinsettia plants was
      also more rapid and resulted in quicker and higher percent mortality of whitefly
      nymphs (89.5-99.6) compared with imidacloprid (14.1-89.2) across all 4 wk.
      However, despite efficient uptake, the efficacy of both systemic insecticides was
      less for citrus mealybug where percent mortality values were <50% among all the
      treatments across the 4 wk. The use of the two systemic insecticides evaluated in
      regards to pest management in horticultural cropping systems is discussed.

PMID- 22606822
TI  - Molecular genetic evidence of formosan subterranean termite (Isoptera:
      Rhinotermitidae) colony survivorship after prolonged inundation.
AB  - Levee breaches because of Hurricane Katrina in 2005 inundated 80% of the city of
      New Orleans, LA. Formosan subterranean termites were observed actively foraging
      within in-ground monitoring stations within months after this period of flooding.
      It was unknown if the activity could be attributed to preexisting colonies that
      survived inundation or to other colonies surviving flooding by being located at
      higher elevations readily invading these territories. Genotypic profiles of 17
      termite colonies collected from eight inundated locations before flooding were
      compared with termite colonies after flooding from the same locations to
      determine Formosan subterranean termite survival after sustained flooding.
      Results indicate that 14 colonies were able to survive inundation for extended
      periods.

PMID- 22606823
TI  - Effect of fipronil on subterranean termite colonies (Isoptera: Rhinotermitidae)
      in the field.
AB  - To assess possible colony-level effects of fipronil, a commonly used nonrepellent
      termiticide, we conducted a field study of eight houses in the Raleigh, NC, area
      with infestations of the eastern subterranean termite Reticulitermes flavipes
      (Kollar) (Isoptera: Rhinotermitidae). We installed an extensive grid of in-ground
      monitoring stations on each property (mean = 68.6 monitors per property) and
      collected samples from these stations as well as from mud tubes in the structure
      and wood debris in the yard for approximately 6 mo. We genotyped all samples by
      using microsatellite markers to identify the number and locations of colonies
      present on each property. Houses were treated with either a full treatment (n =
      5) or exterior/localized interior treatment (n = 3). After treatment, the
      monitors were checked monthly for 3 mo and then quarterly for 3 yr to track the
      fate of colonies. Wood debris in natural areas was checked semiannually for 3 yr.
      All 11 of the treated colonies (those attacking structures) disappeared within 90
      d of treatment and were not found again. These colonies were presumed to be
      eliminated. In contrast, 60% of untreated colonies (those located > 6 m from the
      foundation wall at the time of treatment) continued to persist throughout the
      study, as did 25% of the likely treated colonies (those occupying monitors 0.5 m
      from the foundation wall where the treatment was applied). Our results provide
      strong evidence for potent colony wide effects of fipronil on subterranean
      termites leading to colony suppression and likely colony elimination under field
      conditions.

PMID- 22606824
TI  - Elimination of subterranean termite (Isoptera: Rhinotermitidae) colonies using a
      refined cellulose bait matrix containing noviflumuron when monitored and
      replenished quarterly.
AB  - Using a quarterly (3-mo) monitoring and bait-replenishment interval, 122
      subterranean termite colonies throughout the United States were baited with a
      refined cellulose bait matrix containing 0.5% noviflumuron. All colonies were
      eliminated in less than 1 yr after initiation of baiting as determined by long
      term monitoring and genetic markers. Sixty-three percent of the colonies were
      eliminated during the first quarter after the initiation of baiting and 77% of
      colonies were eliminated after consuming two bait tubes or less. This suggests
      that a single baiting cycle and bait installed in response to a single active
      monitoring device were sufficient to eliminate the majority of colonies. Although
      termites temporarily abandoned stations after depleting bait, workers resumed
      feeding when baits were replenished. Colonies that consumed large amounts of bait
      before elimination foraged into multiple stations, thus allowing adequate amounts
      of bait to sustain feeding. The time to eliminate termite colonies with bait
      replenished quarterly was similar to that previously reported for laminated
      cellulose bait replenished monthly. Our data support the conclusion that
      extending the bait replenishment interval from monthly to quarterly for bait
      tubes with refined cellulose containing 0.5% noviflumuron did not adversely
      impact colony elimination.

PMID- 22606825
TI  - Biochemical basis of organophosphate and carbamate resistance in Asian citrus
      psyllid.
AB  - The Asian citrus psyllid, Diaphorina citri Kuwayama, is a worldwide pest of
      citrus, which vectors the putative causal pathogen of huanglongbing. Current
      management practices warrant continuous monitoring of field populations for
      insecticide resistance. Baseline activities of acetylcholinesterase (AChE),
      general esterase, and glutathione S-transferase as well as sensitivity of AChE to
      selected organophosphate and carbamate insecticides were established for a
      susceptible laboratory strain (Lab) and compared with several field populations
      of D. citri from Florida. The specific activity of AChE in various D. citri
      populations ranged from 0.77 to 1.29 microM min(-1) mg of protein(-1); the Lab
      strain was characterized by the highest activity. Although reduced AChE
      sensitivity was observed in the Lab strain compared with field populations,
      overlap of 95% confidence intervals of I50 values (concentration required for 50%
      AChE activity inhibition) suggests no significant difference in AChE sensitivity
      among all populations tested for a given insecticide. There was no significant
      evidence of target site insensitivity in field populations that were exposed to
      the selected organophosphate and carbamate insecticides tested. The specific
      activity of general esterase and glutathione S-transferase was lowest in the Lab
      strain and was generally comparable to that of the field populations evaluated.
      The current data provide a mode-of-action specific baseline for future monitoring
      of resistance to organophosphate and carbamate insecticides in populations of D.
      citri.

PMID- 22606826
TI  - Chlorantraniliprole susceptibility in Leptinotarsa decemlineata in the north
      Xinjiang Uygur autonomous region in China.
AB  - The Colorado potato beetle (Leptinotarsa decemlineata (Say)) in the north
      Xinjiang Uygur autonomous region has evolved resistance to various types of
      insecticides. Chlorantraniliprole is a novel anthranilic diamide insecticide that
      binds and activates ryanodine receptors. It exhibited excellent efficacy against
      L. decemlineata in several field trails in Europe. In the present paper, the
      susceptibility of L. decemlineata fourth-instar larvae derived from six field
      populations and L. decemlineata adults derived from three field populations to
      chlorantraniliprole was determined by a topical application. The fourth-instar
      larvae were substantially more susceptible to chlorantraniliprole than adults,
      although the range of susceptibility was far greater among the fourth-instar
      larvae. Regarding stomach toxicities, adult beetles were less susceptible to
      chlorantraniliprole than larvae. Chlorantraniliprole was most toxic to second
      instar larvae, followed by third- and fourth-instar larvae. These data suggested
      that the appropriate timing for chlorantraniliprole spraying is the early larval
      stage. Moreover, the synergistic activities of chlorantraniliprole in combination
      with triphenyl phosphate, diethyl maleate, or piperonyl butoxide against fourth
      instar larvae from two field populations and adults from one field population
      were tested. Piperonyl butoxide had synergistic effects with chlorantraniliprole
      against fourth-instar larvae but not against adult beetles. Conversely, triphenyl
      phosphate and diethyl maleate exerted little synergistic effects. It appears that
      there is a potential risk of resistance against chlorantraniliprole resulting
      from cytochrome P450 monooxygenase activity.

PMID- 22606827
TI  - Discrimination of reproductive forms of Thrips tabaci (Thysanoptera: Thripidae)
      by PCR with sequence specific primers.
AB  - In agriculture, although it is important to identify species of pest insects, the
      morphological identification is often difficult. DNA genotyping is useful for the
      identification of species in morphologically indiscriminable species. Thrips
      tabaci (Lindeman) can be divided into two reproductive forms (arrhenotoky and
      thelytoky, each of which different in pesticide resistance) but morphological
      discrimination is not possible. Here, we establish a simple method to
      discriminate the strains based on their mitochondrial DNA sequences. Phylogenetic
      analysis including the T. tabaci and congeneric species provided ancestor
      sequences of each strain of T tabaci. Based on the ancestor sequences, we
      developed a primer set that include strain specific primers on sense strand and
      common primer on anti sense strand. Using this primer set, the strains of 196
      individuals of T. tabaci were successfully assigned to each ofgenotypic forms. As
      the phylogeny and ancestor sequences were based on worldwide samples, this method
      will work well on most populations around the world.

PMID- 22606828
TI  - Transcription and induction profiles of three novel P450 genes in Liposcelis
      bostrychophila (Psocoptera: Liposcelididae).
AB  - The cDNAs of three novel P450 genes, CYP4CB1, CYP4CC1, and CYP4CD1 (GenBank
      accessions EU979550, EU979549, and EU979551, respectively), were sequenced and
      characterized from the psocid Liposcelis bostrychophila Badonnel (Psocoptera:
      Liposcelididae). CYP4CB1, CYP4CC1, and CYP4CD1 contain open reading frames of
      1533, 1512, and 1536 nucleotides that encode 511,504, and 512 amino acid
      residues, respectively. The putative proteins of CYP4CB1, CYP4CC1, and CYP4CD1
      show predicted molecular mass of 59.65, 58.87, and 59.71 kDa, with a theoretical
      isoelectric point of 6.59, 8.80, and 8.84, respectively. The N-terminal
      transmembrane domain was only found in CYP4CB1 suggested it is a typical
      microsomal P450. Phylogenetic analysis showed a close relationship of CYP4CB1,
      CYP4CC1, and CYP4CD1 with CYP4AW1, CYP4L4, and CYP4E2. Quantitative real-time
      reverse transcriptase-polymerase chain reaction indicated that these three genes
      were expressed at all tested developmental stages. In addition, the highest
      expression occurred in the adult stage, which suggested that these three P450
      genes may play important roles in adulthood. The transcripts of CYP4CB1 and
      CYP4CC1 in adult psocids could be induced to the highest level at 36 and 24 h
      after the exposure to deltamethrin and paraoxon-methyl (50% lethal concentration
      [LC50]), respectively, whereas CYP4CD1 remained unchanged. CYP4CD1 transcripts,
      however, increased rapidly at 8 h after aldicarb (LC50) induction and reached the
      peak at 36 h. The induction profiles of the three P450 genes suggested that
      CYP4CB1 and CYP4CC1 are possibly associated with deltamethrin and paraoxonmethyl
      metabolism in psocids, whereas CYP4CD1 is probably involved in aldicarb
      metabolism. However, our assumption needs to be further verified by recombinant
      protein expression of these proteins as well as RNA interference of these genes.

PMID- 22606829
TI  - Host association of Spodoptera frugiperda (Lepidoptera: Noctuidae) corn and rice
      strains in Argentina, Brazil, and Paraguay.
AB  - Spodoptera frugiperda (J.E. Smith) is composed of two genetically distinct
      strains, the so-called corn strain and the rice strain. Whether the two strains
      differ in their host use is unclear, because laboratory experiments have not been
      able to show consistent host performance or preference differences between them,
      and field studies showed high rates of hybridization, as well as some degree
      asymmetric host use. To determine the distribution of the two strains and their
      association with host plants, we collected fall armyworm larvae from different
      crops (corn, rice, alfalfa, and sorghum) and grasses in 15 different localities
      over 4 yr in Argentina, Brazil, and Paraguay. The strain identity was analyzed
      using two polymorphisms in the mitochondrial cytochrome oxidase subunit I gene.
      We identified the corn and rice haplotypes and three types of populations were
      characterized based on the frequencies of the individuals that belonged to any of
      these haplotypes: in 44% of populations the corn haplotype predominated, in 44%
      of populations the rice haplotype was the most frequent, and 11% of populations
      showed both haplotypes at similar proportions. In total, eight populations (47%)
      showed the expected pattern, two populations (12%) were polymorphic within the
      same field, and seven populations (41%) showed the inverse pattern. Taken
      together, there was no consistent pattern of host association between the two
      sympatric genotypes and their respective host plants. This investigation supports
      the need for additional studies to determine which other forces keep the
      genotypes separate, and what is the degree of genetic differentiation between
      these populations.

PMID- 22606830
TI  - Population structure of Aphis spiraecola (Hemiptera: Aphididae) on pear trees in
      China identified using microsatellites.
AB  - The spiraea aphid (Aphis spiraecola Patch) is a primary pest of fruit trees,
      particularly pear trees in China. Despite the economic importance of this pest,
      little is known about its genetic structure or its patterns of dispersal at local
      and regional scales; however, knowledge of these characteristics is important for
      establishing effective control strategies for this pest. The genetic variability
      of 431 individuals from 21 populations on pear trees in China was investigated
      using eight polymorphic microsatellite loci. The high polymorphism of these
      markers was evident from the expected heterozygosity value (He = 0.824) and the
      Polymorphism Information Content (PIC = 0.805), indicating that the spiraea aphid
      maintains a high level of genetic diversity. The analysis of molecular variance
      revealed a middle level of population differentiation (F(ST) = 0.1478) among A.
      spiraecola populations. This result is consistent with the results of the
      STRUCTURE analysis (K = 3), the unweighted pair-group method with arithmetic
      average tree and the Mantel test (r = 0.6392; P < 0.05). Our results indicate
      high levels of genetic exchange in the spiraea aphid, possibly facilitated by
      geography and climate. Our findings emphasize the importance of considering
      regional differences in studies of population structure, even when strong
      isolation-by-distance influences the genetic population structure of species.

PMID- 22606831
TI  - Resistance of wheat lines to Rhopalosiphum padi (Hemiptera: Aphididae) under
      laboratory conditions.
AB  - Bird cherry-oat aphid, Rhopalosiphum padi (L.), a polyphagous species with a
      nearly worldwide distribution, is an important pest of wheat as well as the main
      vector of barley yellow dwarf virus. We evaluated the resistance categories of
      eight wheat lines including antibiosis, antixenosis, and tolerance against R.
      padi under laboratory conditions. The wheat lines tested were ERWYT 88-8, ERWYT
      87-6, and ERWYT 87-4 (resistant); ERWYT 87-1, ERWYT 87-20, and ERWYT 88-11
      (susceptible); ERWYT 88-12 and ERWYT 88-13 (intermediate). In the antibiosis
      experiment, R. padi produced fewest progeny on ERWYT 88-8, ERWYT 87-6, and ERWYT
      87-4 in reproduction period. In the antixenosis test, R. padi performed best on
      ERWYT 87-1, ERWYT 87-20, and ERWYT 88-11. Fewer apterous aphids selected ERWYT 88
      8, ERWYT 87-4, and ERWYT 87-6 lines indicating antixenosis of these lines to R.
      padi. In tolerance experiments, however growth parameters differed between
      treated and untreated seedlings of wheat lines with 10 aphids per day infestation
      during 21-d period, but not among eight wheat lines. The plant resistance index
      values were greatest for ERWYT 88-8 (9.71), followed by ERWYT 87-4 (7.04) and
      ERWYT 87-6 (4.76). ERWYT 88-8, ERWYT 87-6, and ERWYT 87-4 may be important
      sources of R. padi resistance for small grain breeding and integrated pest
      management programs.

PMID- 22606832
TI  - Antibiosis resistance in soybean plant introductions to Dectes texanus
      (Coleoptera: Cerambycidae).
AB  - No soybean cultivars exhibit resistance to larval damage by the cerambycid,
      Dectes texanus LeConte, in the United States. Selected soybean varieties and
      plant introductions (PIs) in maturity groups VI to VIII from the U.S. Department
      of Agriculture National Soybean Germplasm Collection were evaluated for D.
      texanus resistance in a series of field and laboratory experiments from 2005
      through 2008. In field cage experiments, the numbers of oviposition punctures
      (OPs) per plant were determined as indicators of oviposition antixenosis and the
      ratio of OPs per live D. texanus larvae (OP/Lv) served as an indicator of plant
      antibiosis to larvae. A D. texanus-susceptible variety treated with the systemic
      insecticide fipronil was used as a positive antibiosis control. Plant
      introduction PI165673 had the highest OP/Lv ratio, indicating that even if
      oviposition was successful, an antibiosis factor in PI165673 significantly
      reduced egg hatch and the resulting number of live D. texanus larvae. Factorial
      analyses indicated that maturity group is not a significant factor in the
      expression of resistance. Thus, PI165673 appears to be a potential source of
      resistance to D. texanus. In related field studies, the preferred D. texanus
      oviposition site was localized to leaf petioles in the upper four or five nodes
      of the plant canopy. Histomorphological analyses of petiole cross-sections of
      plant introductions PI171451, PI165676, and PI165673 indicated that leaf petiole
      morphology may be related to reduced D. texanus oviposition on petioles of
      PI171451 and PI165676, but that resistance in PI165673 is independent of petiole
      morphology.

PMID- 22606833
TI  - Field and laboratory evaluations of soybean lines against soybean aphid
      (Hemiptera: Aphididae).
AB  - The soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), is a major
      pest of soybean, Glycine max (L.). Merr., that significantly reduces yield in
      northern production areas of North America. Insecticides are widely used to
      control soybean aphid outbreaks, but efforts are underway to develop host plant
      resistance as an effective alternative management strategy. Here, previously
      identified resistant lines were evaluated in laboratory tests against field
      collected populations of soybean aphid and in field-plot tests over 2 yr in South
      Dakota. Six lines previously identified with resistance to soybean aphid-
      Jackson, Dowling, K1639, Cobb, Palmetto and Sennari--were resistant in this
      study, but relatively high aphid counts on Tie-feng 8 in field plots contrasted
      with its previously reported resistance. Bhart-PI 165989 showed resistance in one
      of two laboratory tests, but it had relatively large aphid infestations in both
      years of field tests. Intermediate levels of soybean aphid occurred in field
      plots on lines previously shown to have strong (Sugao Zairai, PI 230977, and D75
      10169) or moderate resistance to soybean aphid (G93-9223, Bragg, Braxton, and
      Tracy-M). Sugao Zairai also failed to have a significant proportion of resistant
      plants in two laboratory tests against aphids field-collected in 2008, but it was
      resistant in laboratory tests with aphids collected in 2002, 2005, and 2006.
      Overall, results showed that lines with Rag (i.e., Jackson) or Rag1 gene (i.e.,
      Dowling) had low aphid numbers, whereas lines with Rag2 (i.e., Sugao Zairai,
      Sennari) had mixed results. Collectively, responses of soybean aphid populations
      in laboratory and field tests in 2008 resembled a virulence pattern reported
      previously for biotype 3 soybean aphids, but virulence in soybean aphid
      populations was variable and dynamic over years of the study. These results,
      coupled with previous reports of biotypes virulent to Rag1, suggest that
      deployment of lines with a single aphid-resistance gene is limited for soybean
      aphid management, and that deployment strategies relying on multiple resistance
      genes may be needed to effectively use plant resistance against soybean aphid.

PMID- 22606834
TI  - Cotton plants expressing a hemipteran-active Bacillus thuringiensis crystal
      protein impact the development and survival of Lygus hesperus (Hemiptera:
      Miridae) nymphs.
AB  - The plant bugs Lygus hesperus Knight (Hemiptera: Miridae) and L. lineolaris
      (Palisot de Beauvois) have emerged as economic pests of cotton in the United
      States. These hemipteran species are refractory to the insect control traits
      found in genetically modified commercial varieties of cotton. In this article, we
      report the isolation and characterization of a 35 kDa crystal protein from
      Bacillus thuringiensis, designated TIC807, which causes reduced mass gain and
      mortality of L. hesperus and L. lineolaris nymphs when presented in an artificial
      diet feeding assay. Cotton plants expressing the TIC807 protein were observed to
      impact the survival and development of L. hesperus nymphs in a concentration
      dependent manner. These results, demonstrating in planta activity of a Lygus
      insecticidal protein, represent an important milestone in the development of
      cotton varieties protected from Lygus feeding damage.

PMID- 22606835
TI  - Effect of soybean varieties on survival and fecundity of western corn rootworm.
AB  - The western corn rootworm, Diabrotica virgifera virgifera LeConte (Coleoptera:
      Chrysomelidae), is a major pest of corn (Zea mays L.) in North America and has
      evolved resistance to crop rotation by ovipositing in alternate crops such as
      soybeans [Glycine max (L.) Merr.]. Through experiments with plants grown in the
      greenhouse and the field, we tested whether soybeans with resistance to the
      soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), affected
      survival, fecundity, and consumption of soybean for D. v. virgifera. Soybean
      varieties tested included those types resistant to A. glycines (Rag1 and
      rag1/rag3) and a susceptible near isoline of the Rag1 variety. Females were
      provided with a diet of corn tissue for 4 d after which they were fed a diet of
      tissue from one of three soybean varieties for 4 d, starved for 4 d, or fed corn
      tissue. When fed greenhouse grown plants, strains differed significantly in
      survival and consumption, but consumption did not differ by variety of soybean.
      Diet treatment only affected fecundity; individuals fed corn continuously had
      greater fecundity than those individuals fed soybeans. In the experiment with
      plants grown in the field, leaf consumption differed among strains and
      individuals fed corn continuously had greater fecundity than the other
      treatments. Soybean varieties with Rag1 and rag1/rag3 resistance to A. glycines
      did not appear to affect the fitness of D. v. virgifera. Thus, planting of these
      A. glycines-resistant soybean varieties should not directly affect the spread of
      rotation-resistant D. v. virgifera.

PMID- 22606836
TI  - Characterization of resistance, evaluation of the attractiveness of plant odors,
      and effect of leaf color on different onion cultivars to onion thrips
      (Thysanoptera: Thripidae).
AB  - Onion thrips, Thrips tabaci Lindeman (Thysanoptera: Thripidae), is a worldwide
      pest of onion, Allium cepa L. In field studies on onion resistance conducted in
      2007 and 2008 using 49 cultivars, 11 showed low leaf damage by T. tabaci. In
      laboratory studies, the 11 cultivars, along with two susceptible checks and four
      additional cultivars, were evaluated to characterize resistance to T. tabaci and
      to determine if color and/or light reflectance were associated with resistance to
      T tabaci. No-choice tests were performed with adults and the numbers of eggs and
      larvae were counted on each cultivar after three and 10 d, respectively. In
      choice tests in which all cultivars were planted together in a circle in a single
      pot, 100 adults were released and the number of adults on each plant was
      evaluated 24 h later. The behavioral response of walking T. tabaci adults to
      plant odors was studied in a glass Y-tube olfactometer. The reflectance spectrum
      of leaves was measured using a UV-VIS spectrophotometer. Results indicate that
      resistant cultivars showed an intermediate-high antibiotic effect to T. tabaci
      and all of them showed a very strong antixenotic effect. There were no
      significant preferences in the response of walking T. tabaci adults to plant
      odors. The two susceptible cultivars had the highest values of leaf reflectance
      for the first (275-375 nm) and second (310-410 nm) theoretical photopigment
      system of T. tabaci, and these values were significantly different from most
      resistant cultivars. These results suggest a strong response of T. tabaci to
      onion cultivars with higher reflectance in the ultraviolet range (270-400 nm).
      Overall, these results appear promising in helping to identify categories of
      resistance to T. tabaci in onions that can be used in breeding programs.

PMID- 22606838
TI  - Insect resistance in sweetpotato plant introduction accessions.
AB  - Fifty-five sweetpotato cultivars, experimental breeding clones, and plant
      introduction (PI) accessions were evaluated in 17 field experiments at the USDA,
      ARS, U.S. Vegetable Laboratory (Charleston, SC; 12 evaluations, 1997-2010), the
      Clemson University, Edisto Research and Education Center (Blackville, SC; two
      evaluations, 1998-1999), and the University of Florida, Tropical Research and
      Education Center (Homestead, FL; three evaluations, 2005-2007). These experiments
      included two insect-susceptible control entries ('Beauregard' and 'SC1149-19')
      and three insect-resistant control cultivars ('Regal,' 'Ruddy,' and 'Sumor'). At
      each location, genotypes differed significantly in the percentage of uninjured
      roots WDS (wireworm, Diabrotica, Systena) index, the percentage of roots damaged
      by the sweetpotato weevil (Cylas formicarius (F.)), the percentage of roots
      damaged by the sweetpotato flea beetle (Chaetocnema confinis Crotch), and the
      percentage of roots damaged by white grub larvae (including Plectris aliena
      Chapin and Phyllophaga spp.). 'SC1149-19' had a significantly lower percentage of
      uninjured roots, a significantly higher WDS index rating, and significantly
      higher percentages of infestation by flea beetles, grubs, and sweetpotato weevils
      than most other sweetpotato genotypes in this study. In addition, 43 of 55
      genotypes had significantly less overall insect damage than 'Beauregard,' one of
      the leading commercial orange-fleshed cultivars in the United States. Ten
      genotypes had significantly less insect injury than 'Picadito,' a commercial
      boniato-type sweetpotato grown extensively in southern Florida. Many of these
      sweetpotato genotypes have high levels of resistance to soil insect pests, and
      they may be useful as sources of insect resistance for use in sweetpotato
      breeding programs.

PMID- 22606837
TI  - Obviation of wheat resistance to the Hessian fly through systemic induced
      susceptibility.
AB  - Unlike most documented plant-insect interactions, Hessian fly-resistance
      [Mayetiola destructor (Say)] in wheat (Triticum aestivum L.) is initiated by a
      gene-for-gene recognition event in which plants carrying a specific R gene
      recognize salivary effectors encoded by a corresponding larval avirulence gene.
      However, dual infestation resulting from oviposition by virulent insects from 5 d
      before to 3 d after oviposition by avirulent insects on the same host plant, lead
      to systemic induced susceptibility, obviation of resistance, and ultimately the
      survival of both virulent and genetically avirulent progeny to adulthood.
      Simultaneous oviposition allowed greater survival of avirulent progeny than
      ovipositions separated by larger intervals. Because of the induction of plant
      resistance, hatch of avirulent larvae before virulent was more detrimental to
      rate of development than hatch of virulent before avirulent larvae. Obviation of
      resistance was not localized to the leaf being attacked by the virulent larvae,
      but also functioned across spatial distance into younger leaves. This research
      suggests that virulent Hessian fly larvae directly suppress the defense response
      of wheat, thus providing a refuge for avirulent genotypes, preserving diversity
      in field populations and increasing durability of deployed resistance genes.

PMID- 22606840
TI  - Insecticidal potential of natural zeolite and diatomaceous earth formulations
      against rice weevil (Coleoptera: Curculionidae) and red flour beetle (Coleoptera:
      Tenebrionidae).
AB  - Insecticidal potential of natural zeolites and diatomaceous earths originating
      from Serbia against Sitophilus oryzae (L.) and Tribolium castaneum (Herbst) was
      evaluated. Two natural zeolite formulations (NZ and NZ Modified) were applied to
      wheat at rates of 0.50, 0.75, and 1.0 g/kg, while two diatomaceous earth (DE)
      formulations (DE S-1 and DE S-2) were applied at rates of 0.25, 0.50, 0.75, and
      1.0 g/kg. A bioassay was conducted under laboratory conditions: temperature of 24
      +/- 1 degrees C, relative humidity in the range 50-55%, in tests with natural
      zeolites, and 60-65%, in tests with DEs, and in all combinations for progeny
      production. Mortality was assessed after 7, 14, and 21 d of insect contact with
      treated wheat, and the total mortality after an additional 7-d recovery on
      untreated broken wheat. Progeny production was also assessed after 8 wk for S.
      oryzae and 12 wk for T. castaneum. The highest mortality for S. oryzae and T.
      castaneum was found after the longest exposure period and 7 d of recovery, on
      wheat treated with NZ at the highest rate and DEs at rates of 0.50 -1.0 g/kg.
      Progeny reduction higher than 90% was achieved after 14 and 21 d of contact of
      both beetle pests with wheat treated with DE S-1 at 0.50-1.0 g/kg and DE S-2 at
      0.75-1.0 g/kg, while the same level of reduction was achieved only for T.
      castaneum after its contact with the highest rate of NZ formulation. NZ Modified,
      applied even at the highest rate, revealed much lower insecticidal potential.

PMID- 22606839
TI  - Temporal analysis of sesquiterpene emissions from manuka and phoebe oil lures and
      efficacy for attraction of Xyleborus glabratus (Coleoptera: Curculionidae:
      Scolytinae).
AB  - Redbay ambrosia beetle, Xyleborus glabratus Eichhoff, is an exotic wood-borer
      that vectors the fungal agent (Raffaelea lauricola) responsible for laurel wilt.
      Laurel wilt has had severe impact on forest ecosystems in the southeastern United
      States, killing a large proportion of native Persea trees, particularly redbay
      (P. borbonia) and swampbay (P. palustris), and currently poses an economic threat
      to avocado (P. americana) in Florida. To control the spread of this lethal
      disease, effective attractants are needed for early detection of the vector. Two
      12-wk field tests were conducted in Florida to evaluate efficacy and longevity of
      manuka and phoebe oil lures, and to relate captures of X. glabratus to release
      rates of putative sesquiterpene attractants. Two trap types were also evaluated,
      Lindgren funnel traps and sticky panel traps. To document lure emissions over
      time, a separate set of lures was aged outdoors for 12 wk and sampled
      periodically to quantify volatile sesquiterpenes using super-Q adsorbant and gas
      chromatography-mass spectroscopy analysis. Phoebe lures captured significantly
      more X. glabratus than manuka lures, and sticky traps captured more beetles than
      funnel traps. Phoebe lures captured X. glabratus for 10-12 wk, but field life of
      manuka lures was 2-3 wk. Emissions of alpha-copaene, alpha-humulene, and cadinene
      were consistently higher from phoebe lures, particularly during the 2-3 wk window
      when manuka lures lost efficacy, suggesting that these sesquiterpenes are primary
      kairomones used by host-seeking females. Results indicate that the current
      monitoring system is suboptimal for early detection of X. glabratus because of
      rapid depletion of sesquiterpenes from manuka lures.

PMID- 22606841
TI  - Comparative mortality of diapausing and nondiapausing larvae of Plodia
      interpunctella (Lepidoptera: Pyralidae) exposed to monoterpenoids and low
      pressure.
AB  - Monoterpenoids and low pressure have each been demonstrated to cause mortality of
      stored-product insect pests. The current report investigated the prospects of
      integrating the two methods in the management of diapausing and nondiapausing
      larvae of Plodia interpunctella (Hubner). In a separate experiment, the larvae
      were exposed to 35.5 mmHg in Erlenmeyer flasks at 19 and 28 degrees C for times
      ranging from 30 min to 96 h. Another set of experiments was conducted to
      investigate the toxicity of exposing P. interpunctella larvae to monoterpenoids
      including E-anethole, estragole, S-carvone, linalool, L-fenchone, geraniol, gamma
      terpinene, and DL-camphor alone or in combination with low pressure (50 mmHg).
      Lethal times (LT) determined by subjecting time-mortality data to probit analyses
      were shortened to half when both diapausing and nondiapausing larvae were exposed
      to low pressure at 28 degrees C compared with 19 degrees C. Exposure of
      diapausing larvae to a monoterpenoid alone, with the exception of DL-camphor and
      estragole, at a concentration of 66.7 microl/1L of volume required > 30 h to
      generate 99% mortality at 19.0 +/- 0.8 degrees C. However, the LT99 values for
      diapausing and nondiapausing larvae exposed to combinations of DL-camphor or
      estragole and low pressure were considerably shortened. Combinations involving
      the rest of the monoterpenoids investigated and low pressure did not generate
      LT99 that were shorter than those of the control, which was low pressure only.
      These results suggest that integrating low pressure with DL-camphor or estragole
      could be a new method for the control of diapausing larvae of P. interpunctella
      at cooler temperatures.

PMID- 22606842
TI  - Influence of environmental and physical factors on capture of Tribolium castaneum
      (Coleoptera: Tenebrionidae) in a flour mill.
AB  - Variation in environmental and physical factors within food processing facilities
      can influence both the distribution of stored-product pests and trapping
      efficiency. Data from a long-term Tribolium castaneum (Herbst) (Coleoptera:
      Tenebrionidae) monitoring program was used to evaluate spatial variation in
      captures among trap locations and to determine relationships with environmental
      and physical variables. From the complete monitoring data set, different subsets
      were created for the cool and warm seasons, and period of time when environmental
      and physical factors were measured (2009-2010), with all data sets showing
      significant differences among trap locations in terms of beetle captures and
      proportion of time that traps exceeded 2.5 beetles per trap per monitoring
      period. There was also considerable temporal variation in distribution among the
      different levels of the mill. Among the environmental and physical variables
      measured, mean temperature and flour dust accumulation showed the most
      significant positive relationships with variation of beetle captures at trap
      locations. More beetles were captured in traps located in close proximity to
      milling equipment. Presence of equipment near traps was also associated with an
      increase in flour dust accumulation and temperature. Overall the environmental
      and physical factors seemed to have a limited influence on variation in captures
      among trap locations, with temporal variation in distribution perhaps
      overwhelming potential influences of local trap conditions.

PMID- 22606843
TI  - Impact of varying levels of sanitation on mortality of Tribolium castaneum eggs
      and adults during heat treatment of a pilot flour mill.
AB  - The influence of sanitation on responses of life stages of the red flour beetle,
      Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae), an economically
      important pest in flour mills, was investigated in a pilot flour mill subjected
      to two, 24-h heat treatments. One hundred eggs or 100 adults of T. castaneum were
      exposed inside each 20-cm diameter by 15-cm high PVC rings holding 0.1-, 0.2-,
      1.0-, 3.0-, 6.0-, and 10.0-cm-deep wheat flour to simulate different sanitation
      levels that may exist in a flour mill. These rings were placed on the first and
      third floors of a pilot flour mill. On the first floor, temperatures inside rings
      with eggs reached 50 degrees C in 7-11 h only in 0.1- and 0.2-cm-deep flour
      treatments. In all other treatments the maximum temperatures attained generally
      were below 50 degrees C and inversely related to flour depth. Adults of T.
      castaneum on this floor were less susceptible than eggs. The egg mortality
      decreased linearly with an increase in flour depth, whereas that of adults
      decreased exponentially. All eggs and adults in rings on the third floor were
      killed irrespective of flour depth, because temperatures inside rings reached 50
      degrees C in 15-17 h and were held above 50 degrees C for 6-8 h with the maximum
      temperatures ranging between 55.0 and 57.0 degrees C. Although the protective
      effects of flour on survival of T. castaneum eggs and adults were evident only if
      temperatures did not reach 50 degrees C, removal of flour accumulations is
      essential to improve heat treatment effectiveness.

PMID- 22606844
TI  - Susceptibility of Tribolium castaneum life stages exposed to elevated
      temperatures during heat treatments of a pilot flour mill: influence of
      sanitation, temperatures attained among mills floors, and costs.
AB  - The influence of sanitation on responses of life stages of the red flour beetle,
      Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae), was investigated in a
      pilot flour mill subjected to three, 24-h heat treatments by using forced-air gas
      heaters fueled by propane. Two sanitation levels, dusting of wheat flour and 2-cm
      deep flour, were created in 25 plastic bioassay boxes, each holding eggs, young
      larvae, old larvae, pupae, and adults of T. castaneum plus two temperature
      sensors. Data loggers (48) were placed on the five mill floors to record air
      temperatures. The time required to reach 50 degrees C, time above 50 degrees C,
      and the maximum temperature among mill floors and in bioassay boxes were
      measured. The maximum temperature in bioassay boxes and in the mill was lower on
      the first floor than on other floors. This trend was apparent in time required to
      reach 50 degrees C and time above 50 degrees C, especially in compartments with 2
      cm-deep flour. The mean +/- SE mortality of T. castaneum life stages on the first
      floor was 55.5 +/- 12.9-98.6 +/- 0.8%; it was 93.2 +/- 6.7-100 +/- 0.0% on other
      floors. Adults were the least susceptible stage. Mortality of T. castaneum stages
      in compartments with 2-cm-deep flour was generally lower than those with flour
      dust. Costs for the three heat treatments ranged from US$27,438 to $28,838. An
      effective heat treatment can be conducted within 24 h, provided temperatures on
      mill floors reach 50 degrees C in 8-12 h and are held above 50 degrees C for at
      least 10-14 h, with maximum temperatures held between 50 and 60 degrees C.

PMID- 22606845
TI  - Residual efficacy of methoprene for control of Tribolium castaneum (Coleoptera:
      Tenebrionidae) larvae at different temperatures on varnished wood, concrete, and
      wheat.
AB  - The residual efficacy of the juvenile hormone analog methoprene (Diacon II) was
      evaluated in bioassays using larvae of Tribolium castaneum (Herbst) (Coleoptera:
      Tenebrionidae) exposed on unsealed concrete or varnished wood treated with a
      liquid formulation and held at different temperatures. When these two types of
      surfaces were stored at 20, 30 or 35 degrees C for 0-24 wk, the percentage of
      adult emergence on concrete increased with time. In contrast, there was no adult
      emergence from larvae exposed to varnished wood at 24 wk after treatment at any
      of these temperatures. The presence of flour reduced residual efficacy of
      methoprene on concrete, but not on varnished wood, with no differences between
      cleaning frequencies. Methoprene was also stable for 48 h on concrete held at 65
      degrees C and wheat, Triticum aestivum L., held at 46 degrees C. Results show
      that methoprene is stable at a range of temperatures commonly encountered in
      indoor food storage facilities and at high temperatures attained during
      insecticidal heat treatments of structures. The residual persistence of
      methoprene applied to different surface substrates may be affected more by the
      substrate than by temperature.

PMID- 22606846
TI  - Efficacy of cyromazine to control immature stable flies (Diptera: Muscidae)
      developing in winter hay feeding sites.
AB  - Hay mixed with manure and urine residues at sites where hay has been provided as
      supplemental winter feed for cattle provide an excellent substrate for the
      development of immature stable flies, Stomoxys calcitrans (L.). Such sites are
      primary sources of early summer stable flies in the central United States and no
      effective measures are currently available to control fly development in them. A
      single application of granular cyromazine in May provided 97% reduction in the
      number of adult stable flies emerging from hay feeding sites. Stable fly control
      did not decline during the 12 wk season. A small decline in control was observed
      relative to anthomyiid, sarcophagid, and syrphid flies developing in the hay
      feeding sites. However, none of those flies are considered to be pests and > or =
      50% control of those flies was maintained for 65 d after application. Cyromazine
      offers a safe and affordable option for the control of immature stable flies
      developing in winter hay feeding sites. Controlling those flies should reduce the
      estimated $2 billion per year of lost production in U.S. cattle industries
      attributable to stable flies.

PMID- 22606847
TI  - Effects of temperature on mortality of larval stable fly (Diptera: Muscidae)
      caused by five isolates of Bacillus thuringiensis.
AB  - We examined the effects of temperature on mortality of larval stable fly
      [Stomoxys calcitrans (L.)] caused by Bacillus thuringiensis tolworthi 4L3, B. t.
      darmastedensis 4M1, B. t. thompsoni 401, B. t. thuringiensis HD2, and B. t.
      kurstaki HD945. At moderate doses, mortality caused by all isolates ranged from
      87 to 99% at 15 degrees C and declined to 29-63% as temperature increased to 30
      degrees C. A similar pattern was seen when a higher dose was used, except that
      the reduction in mortality at warmer temperatures was not as great as was seen
      with the moderate doses. Insecticidal activity of each isolate against first
      instar larvae was reduced by only 5-15% after 5 d in the medium. Mortality of
      second- and third-instar larvae ranged from 2 to 21%, suggesting the isolates
      were less effective against larger larvae.

PMID- 22606848
TI  - Ergonomics and posture and pain--oh my!

PMID- 22606849
TI  - Education: the key to our success.

PMID- 22606850
TI  - Letter to Clifton Simmons regarding his article published in CRANIO, 2012; 1(1):9
      24.

PMID- 22606851
TI  - Comments on Dr. Matos, et al.'s article (pps. 255-260) in CRANIO october 2011
      issue.

PMID- 22606852
TI  - Myofascial pain of the jaw muscles: comparison of short-term effectiveness of
      botulinum toxin injections and fascial manipulation technique.
AB  - A randomized controlled trial was performed to compare the short-term
      effectiveness of botulinum toxin injections and physiatric treatment provided by
      means of Fascial Manipulation techniques in the management of myofascial pain of
      jaw muscles. Thirty patients with a Research Diagnostic Criteria for
      Temporomandibular Disorders (RDC/TMD) diagnosis of myofascial pain were
      randomized to receive either single-session botulinum toxin injections (Group A)
      or multiple-session Fascial Manipulation (Group B). Maximum pain levels (VAS
      ratings) and jaw range of motion in millimeters (maximum mouth opening,
      protrusion, right and left laterotrusion) were assessed at baseline, at the end
      of treatment, and at a three-month follow-up. Both treatment protocols provided
      significant improvement over time for pain symptoms. The two treatments seem to
      be almost equally effective, Fascial Manipulation being slightly superior to
      reduce subjective pain perception, and botulinum toxin injections being slightly
      superior to increase jaw range of motion. Differences between the two treatment
      protocols as to changes in the outcome parameters at the three-months follow-up
      were not relevant clinically. Findings from the present investigation are in line
      with literature data supporting the effectiveness of a wide spectrum of
      conservative treatment approaches to myofascial pain of the jaw muscles. Future
      studies on larger samples over a longer follow-up span are needed on the way to
      identify tailored treatment strategies.

PMID- 22606853
TI  - Age-related differences in temporomandibular disorder diagnoses.
AB  - The purpose of the current study was to evaluate the pattern of age distribution
      of temporomandibular disorders (TMD) and to identify prevalence peaks for the
      different diagnoses. The study sample (N = 383; F:M ratio = 3.9; mean age range
      41.7 +/- 17 years) consisted of patients seeking treatment for TMD and who were
      assessed in accordance with the Research Diagnostic Criteria for
      Temporomandibular Disorders (RDC/TMD) version 1.0 guidelines. The sample was
      divided into four age groups on the basis of percentile-derived intervals to
      compare prevalence of different diagnoses in relation to age. The pattern of
      clinical diagnoses changed with increasing age. The peculiar distribution of
      RDC/TMD axis I diagnoses, with relation to age, mainly affected the disorders
      trend of groups II and III, with the former decreasing with age from about 62% to
      40% and the latter increasing from 75% to almost 95%. Two distinct age peaks were
      identified for the prevalence of the main clinical marker of group III diagnosis
      of arthrosis/arthritis, viz., joint crepitus sounds (N = 104, mean age range 51.9
      +/- 14.5), and for the prevalence of all other diagnoses in patients without
      joint crepitus (N = 279, mean age range 37.9 +/- 16.4). The hypothesis that TMD
      patient populations may be composed of at least two diagnostic subgroups in
      relation to age, and that the presence of clinically diagnosed degenerative joint
      disorders may be a key discriminating factor, was supported. The external
      validity of the results from this investigation needs to be confirmed by
      multicenter and cross-cultural studies.

PMID- 22606854
TI  - Size and form of the human temporomandibular joint in African-Americans and
      Caucasians.
AB  - The aim of this study was to examine contemporary human skull material for
      possible differences between Caucasians and African-Americans in respect to size
      and form of the temporomandibular condyles. The material consisted of a total of
      129 Caucasian skulls (94 males and 35 females) and 76 African-American skulls (40
      males and 36 females). Their mean age at death was 46 years for the Caucasians
      (range: 19-89 years) and 37 years for the African-Americans (range: 18-70 years).
      The mediolateral and anteroposterior dimensions of the 410 condyles were
      measured, and the condylar form was estimated using both anterior and superior
      views. No statistically significant differences could be found between Caucasians
      and African-Americans for any of the recorded variables. In conclusion, the
      present results lend no support for the existence of ethnic differences between
      the two groups examined in respect of temporomandibular joint size and form. It
      is likely that other factors such as evolution, overall cranial size, dietary
      differences, and genetic factors, irrespective of ethnicity, can explain the
      differences found in different skull samples.

PMID- 22606855
TI  - Comparison of subjective symptoms of temporomandibular disorders in young
      patients by age and gender.
AB  - The authors assessed the subjective symptoms of temporomandibular disorders
      (TMDs) in 167 young patients using self-reported forms, with five ratings for
      pain intensity and six ratings for difficulty in activities of daily living
      (ADL), to compare TMD symptoms according to gender and three age groups: group 1:
      6- to 12-year-olds (juvenile); group 2: 13- to 15-year-olds (early adolescent);
      group 3: 16- to 18-year-olds (late adolescent). No significant gender differences
      were found in the symptoms among the groups, except for headache and neck pain in
      group 3. Pain intensity and tightness in the jaw/face, headache, and neck pain,
      as well as the ADL-related difficulty in prolonged jaw opening, eating soft/hard
      foods, and sleeping significantly differed among the groups (p < 0.01, Kruskal
      Wallis test). Therefore, late adolescent patients with TMDs have higher pain
      intensity in the orofacial region and greater difficulty in ADL than do early
      adolescent and juvenile patients with TMDs.

PMID- 22606856
TI  - The relationship between malocclusion, benign joint hypermobility syndrome,
      condylar position and TMD symptoms.
AB  - The current study investigated the association between temporomandibular
      disorders, malocclusion patterns, benign joint hypermobility syndrome and the
      initial condylar position. One hundred sixty-two subjects were analyzed using the
      Rocabado Temporomandibular Pain Analysis; Helkimo Index parameters; the Carter
      Wilkinson modified test; and a mounting cast with condylar position indicator
      registration (MPI). The study revealed a significant association between: 1.
      Delta H, skeletal pattern (p = 0.034); 2. Delta Y, transversal malocclusion (p =
      0.04); 3. right and left, Delta Z, right and left posteroinferior synovial pain
      (p < 0.05); 4. hypermobility scale, gender (p < 0.001), malocclusion pattern (p =
      0.021); 5. TMJ function impairment, gender (p = 0.043); 6. sagittal malocclusion
      pattern, right temporomandibular pain analysis joint (TPAJ) (p = 0.0034); 7. TMJ
      function impairment, left and right TPAJ (p = 0.007); and 8. mandibular motion,
      left and right TPAJ (p = 0.035, p = 0.015). The conclusion was that anterior
      crossbite and condylar displacements in the vertical plane are risk factors in
      developing TMJ symptoms.

PMID- 22606857
TI  - The concurrency of temporal tendinitis with TMD.
AB  - Temporomandibular disorder (TMD) is a type of orofacial pain that can originate
      from a number of craniofacial mandibular structures. These include the TM joints,
      the muscles of mastication, related nerves, tendons, ligaments, bones and teeth.
      Symptoms include impaired jaw function, TM joint noises and pain, limited
      opening, often with jaw deviations or deflections to the affected side. Temporal
      tendinitis is a disorder of the fibrous insertion of the temporalis muscle
      tendons on the coronoid process of the mandible that is characterized by both
      inflammation and degeneration. Sometimes, temporal tendinitis can be the primary
      disease entity, but the authors found that it frequently coexists with TMD. This
      retrospective study was undertaken to determine the prevalence of temporal
      tendinitis with TMD. The charts of 449 patients diagnosed with TMD were reviewed
      to determine the incidences of temporal tendinitis. The referred pain sites and
      their incidences were also determined.

PMID- 22606858
TI  - New approaches to dental occlusion: a literature update.
AB  - Because the study of occlusion is a basic area in dentistry, its components,
      physiology and integration with the stomatognathic system (SS) have been the
      subject of interest in the scientific literature. However, the focus given to
      this issue has changed substantially. Currently, new approaches have been
      proposed in order to update concepts and to demonstrate the full integration and
      functionality of this system within the human body. With this approach, the
      authors proposed the following literature review aimed at gathering recent papers
      (published from 2000 to 2010) with innovative study design, methodology and/or
      results. The authors' intention is to show the main trends in the study of
      occlusion and the SS. The literature review was conducted in the PubMed database,
      using initially the term "dental occlusion" as a key-word. As items of interest
      were found, papers were grouped by categories according to their main subject
      matter. Forty-seven articles were selected and the main categories obtained were:
      1. functional magnetic resonance imaging (fMRI); 2. brain activation; 3.
      masticatory/occlusal function; 4. body function and physical performance; 5.
      osseoperception; 6. finite element models; and 7. occlusion and pain. Observing
      the current literature, the authors found that recent studies present different
      methodologies for the study of occlusion. These studies have allowed scientists
      to obtain detailed information about the physiology of occlusion and the SS, as
      well as about its integration in the body. Research in this area should be
      continued in order to clarify, in detail, the role of each component of the SS
      and its interaction with human physiology.

PMID- 22606859
TI  - An excessive coronoid hyperplasia with suspected traumatic etiology resulting in
      mandibular hypomobility.
AB  - There are multiple theories as to the causes of coronoid process hyperplasia of
      the mandible, including trauma, temporalis muscle hyperactivity, hormonal
      stimulus, and genetic inheritance. The excess growth of the coronoid process can
      cause impingement on the zygomatic processes and may result in mandibular
      hypomobility. A case of an excessive unilateral coronoid hyperplasia with
      suspected traumatic etiology, which was successfully treated by coronoidectomy
      and postoperative physiotherapy, is presented. The patient was a 21-year-old man
      whose maximum mouth opening was 23 mm. The attachments of the temporalis muscle
      were stripped and the coronoid process was accessed using the Al-Kayat and
      Bramley approach. The coronoid process was then resected via an intraoral
      pathway. One week after surgery, physiotherapy was started and the maximum mouth
      opening had increased to 38 mm. In the case presented, a coronoidectomy with
      postoperative physiotherapy for treatment of coronoid process hyperplasia
      produced satisfactory results in the correction of coronoid-malar interference.

PMID- 22606861
TI  - Cardiovascular risk score and cardiovascular events among airline pilots: a case
      control study.
AB  - BACKGROUND: A cardiovascular risk prediction score is routinely applied by
      aviation authorities worldwide. We examined the accuracy of the Framingham-based
      risk chart used by the New Zealand Civil Aviation Authority in predicting
      cardiovascular events among airline pilots. METHODS: A matched case-control
      design was applied to assess the association of 5-yr cardiovascular risk score
      and cardiovascular events in Oceania-based airline pilots. Cases were pilots with
      cardiovascular events as recorded on their medical records. Each case was age and
      gender matched with four controls that were randomly selected from the pilot
      population. To collect data before the events, 5-yr retrospective evaluations
      were conducted. RESULTS: Over a 16-yr study period we identified 15 cases of
      cardiovascular events, 9 (60%) of which were sudden clinical presentations and
      only 6 (40%) of which were detected using cardiovascular screening. There were 8
      cases (53%) and 16 controls (27%) who had a 5-yr risk of > or = 10-15%. Almost
      half of the events (7/15) occurred in pilots whose highest 5-yr risk was in the 5
      10% range. Cases were 3.91 times more likely to have highest 5-yr risk score of >
      or =10-15% than controls (OR = 3.91, 95% CI 1.04-16.35). The accuracy of the
      highest risk scores were moderate (AUC = 0.723, 95% CI 0.583-0.863). The cutoff
      point of 10% is valid, with a specificity of 0.73, but low sensitivity (0.53).
      CONCLUSION: Despite a valid and appropriate cutoff point, the tool had low
      sensitivity and was unable to predict almost half of the cardiovascular events.

PMID- 22606860
TI  - Intraoral schwannoma: review of the literature and presentation of a rare case.
AB  - Schwannomas, also known as neurilemomas or neurilemmomas, are relatively
      uncommon, slow-growing benign tumors. Whereas, about one-third of all
      extracranial Schwannomas are found in the head and neck region, a few intraoral
      Schwannomas are reported in the literature. This article contributes to a review
      regarding the current literature and the report of a rare case. The literature
      searches were performed using the National Library of Medicine. Keywords used in
      the search were: schwannoma or neurilemmoma and intraoral. The literature search
      revealed 16,906 reports containing the word schwannoma; however, only 1,117
      articles described this tumor entity in the "head and neck" region. The search
      item intraoral, in addition to schwannoma or neurilemmoma, were found in only 29
      reports. In most cases, intraoral schwannomas are benign, slowly growing tumors.
      The treatment of choice is surgical excision. However, malignant schwannomas can
      also occur, and need a radical resection and a dissection of the regional lymph
      nodes.

PMID- 22606862
TI  - Heat production and heat loss responses to cold water immersion after 35 days
      horizontal bed rest.
AB  - INTRODUCTION: Bed rest is a terrestrial experimental analogue of unloading
      experienced during exposure to microgravity. Such unloading causes atrophy
      predominantly of the postural muscles, especially those of the lower limbs.
      METHODS: We tested the hypothesis that 35 d horizontal bed rest alters
      thermoregulatory responses of subjects (N = 10) immersed in 15 degrees C water,
      particularly the heat produced by the shivering tremor of the skeletal muscles.
      Before and after bed rest we measured the thickness of the gastrocnemius medialis
      (GM), vastus lateralis (VL), tibialis anterior (TA), and biceps brachii (BB)
      muscles by ultrasonography. During the immersions, we monitored rectal and skin
      temperatures, heat flux, heart rate, and oxygen uptake. RESULTS: After bed rest,
      muscle thickness decreased significantly by 12.2 +/- 8.8% and 8.0 +/- 9.1% in the
      GM and VL, respectively. No changes were observed in the TA and BB muscles. The
      35-d bed rest caused a significant reduction in aerobic power, as reflected in
      maximal oxygen uptake. There were no significant differences in any of the
      observed thermoregulatory responses between the pre- and post-bed rest
      immersions. CONCLUSIONS: Cardiovascular and muscular deconditioning had no effect
      on the heat production and heat loss responses. Due to the significant reduction
      in the mass of the muscles in the lower limbs, concomitant with no change in heat
      production, we conclude that leg muscles do not play a significant role in
      shivering thermogenesis.

PMID- 22606863
TI  - Cognitive cues and visually induced motion sickness.
AB  - BACKGROUND: The importance of cognitive processing of orientation cues in
      visually induced motion sickness and vection is often overlooked. Upright versus
      inverted visual scenes containing cues of different levels of salience were
      compared. METHODS: Panoramic scenes of 360 degrees were projected in the visual
      equivalent to the nauseogenic situation of rotating about an axis tilted from the
      vertical with a field of view of 84 degrees rotating at 0.2 Hz (72 degrees x s(
      1)). Exposures were for 10 min or until moderate nausea developed. The design was
      counterbalanced repeated measures. Pilot Study: Subjects (N = 12) viewed visual
      conditions: a distant bland coastline scene as from an aircraft, tilted 30
      degrees (Up); the same scene but inverted (Invert); and the scene morphed with no
      obvious orientation cues (Abstract). Main Experiment: Subjects (N = 22) viewed a
      city street scene containing numerous unambiguous and strong verticality cues
      under two conditions: upright (Up) and inverted (Invert), with 18 degrees tilt of
      rotational axis. RESULTS: Pilot Study: there were no significant differences
      between conditions in time (mean +/- SD min) to nausea endpoint (Up: 7.4 +/- 3.1;
      Invert: 7.1 +/- 3.1;Abstract: 7.8 +/- 2.4), nor for total symptom scores, nor for
      vection. Main Experiment: the upright scene was significantly more nauseogenic
      than the inverted, with shorter times to nausea endpoint (Up: 8.7 +/- 2.3;
      Invert: 9.2 +/- 2.2) and greater total symptom scores. Vection was marginally
      greater for Up than Invert. CONCLUSIONS: Salient and unambiguous higher order
      cognitive cues may modulate the development of motion sickness induced by
      optokinetic stimuli. There was no one-to-one correspondence between vection and
      motion sickness.

PMID- 22606864
TI  - Hypergravity conditioning on ileal movements in rats.
AB  - INTRODUCTION: Stress is a common trigger for various physiological disturbances,
      including feeding disorders. One of the possible mechanisms for feeding disorders
      may be linked to changes in intestinal movement caused by stress. Therefore, here
      we investigated in vitro stress-induced changes in ileal movement. METHODS: Rats
      (female Wistar, SPF) were divided into Control (1 G) and hypergravity (hyperG)
      groups. HyperG stress was applied daily for 10 min by a centrifugal apparatus for
      1 to 30 d. Under barbiturate anesthesia, a 1-cm long section of the ileum was
      isolated and fixed in a Magnus-type chamber filled with tyrode solution.
      Intestinal movement was evoked by applying acetylcholine (Ach, 10(-7)-10(-5) g x
      ml(-1)). Antagonistic effects of adrenalin (Adr, 10(-4) g x ml(-1)) on the Ach
      evoked movements were also observed. RESULTS: Clear ileum movements were observed
      after Ach application. The movement pattern was phasic (early) and tonic (late).
      Peak amplitude of the phasic wave was dose-dependent on the Ach concentration. No
      significant differences in the averaged peak amplitude between control and hyperG
      groups were observed. The peak amplitude was decreased by Adr application in both
      the control and hyperG groups; however, the degree of the decrement was higher in
      hyperG than in control at 1 d after stress loading. DISCUSSION: The present study
      indicates that gravity stress modified ileal movement. Although basic ileum
      movements evoked by Ach were not influenced by stress, they were modified by Adr
      at a quite early stage after stress loading, suggesting an increase in the
      sensitivity of Adr receptors, but not of Ach receptors in the ileum.

PMID- 22606865
TI  - Cardiovascular and pulmonary responses to increased acceleration forces during
      rest and exercise.
AB  - BACKGROUND: The reduced cardiac output (CO) secondary to increased acceleration
      forces (+Gz) has applicability to daily life and pathophysiology. Increased +Gz
      and reduced CO affect the lung, resulting in reduced oxygen transport. A variety
      of studies have examined tolerance to high +Gz. METHODS: The present study
      examines the effect of +1 to +3 Gz on steady-state cardiopulmonary variables at
      rest and while exercising at +2 Gz and +3 Gz. This study also looks at the
      deterioration of steady-state cardiopulmonary variables with sustained increased
      +Gz and after de-training in eight male centrifuge trained subjects. RESULTS: CO
      (-1.53 L x min(-1)/+Gz), stroke volume (-30 ml/+Gz, SV), and pulmonary diffusing
      capacity (-3.42 ml x mmHg(-1)/+Gz, DL(co)) decreased linearly with increased +Gz
      at rest while heart rate (23 bpm/+Gz, HR), total peripheral resistance (0.0095
      TPRU/Gz TPR), mean arterial pressure (13.2 mmHg/+Gz, MAP), and ventilation (4.13
      L x min(-1)/+Gz, V(E)) increased linearly. During graded exercise, CO and SV
      increased less at +2 Gz and +3 Gz while MAP and VE increased more. Failure to
      endure increased +Gz and the effects of de-training were primarily due to the
      inability to regulate MAP. DISCUSSION: The incremental increase in increased +Gz
      from 1 to 3 resulted in increased MAP, which was accomplished by increasing TPR
      sufficiently so as to offset the reduced CO. The effects of increased +Gz and
      reduced CO compromised lung function and oxygen transport (-18-30%), thus
      compromising exercise capacity. The failure to regulate MAP at lower increased
      +Gz levels resulted in intolerance to higher increased +Gz.

PMID- 22606866
TI  - Flight experience and the perception of pitch angular displacements in a gondola
      centrifuge.
AB  - BACKGROUND: It has been shown that flight experience may induce an adaptation of
      the vestibular system. The aim of the present work was to elucidate whether
      pilots, in comparison with non-pilots, have an increased responsiveness to
      angular displacement canal stimuli in the pitch plane during a conflict between
      the otolith organs and the semicircular canals. METHODS: In a large swing-out
      gondola centrifuge, eight non-pilots, eight fighter pilots, and eight helicopter
      pilots underwent three runs (2 G, 5 min) heading forward, centripetally, and
      centrifugally. The direction of the gravitoinertial force was constant with
      respect to the subject. The visually perceived eye level (VPEL) was measured in
      darkness by means of an adjustable luminous dot. RESULTS: In the forward position
      the three groups produced similar results. After acceleration there was a
      sensation of backward tilt and an increasing depression of VPEL. This effect was
      smaller in the centripetal position and larger in the centrifugal position. The
      difference in VPEL between the opposite positions constitutes a measure of the
      ability to sense the pitch angular displacement canal stimulus related to the
      swing out of the gondola (60 degrees). This difference was most pronounced
      initially at the 2-G plateau (mean +/- SD): 13.5 +/- 12.9 degrees (non-pilots),
      41.6 +/- 21.1 degrees (fighter pilots), and 19.5 +/- 14.0 degrees (helicopter
      pilots). There was no significant difference between non-pilots and helicopter
      pilots. Fighter pilots differed significantly from both non-pilots and helicopter
      pilots. CONCLUSION: Vestibular learning effects of flying may be revealed in a
      centrifuge. Fighter pilots had an increased ability, as compared to non-pilots
      and helicopter pilots, to perceive pitch angular displacements.

PMID- 22606867
TI  - High sensitivity C-reactive protein in airline pilots with metabolic syndrome.
AB  - BACKGROUND: Airline pilots belong to a relatively high-income, healthy
      population, with sedentary behavior during their flight activity, who often eat
      unsuitable meals. We assessed the prevalence of metabolic syndrome (MS) and the
      levels of high sensitivity C-reactive protein (hs-CRP) in a population of airline
      pilot in order to study a possible relationship between the hs-CRP and MS.
      METHODS: MS was established according to the National Cholesterol Education
      Program, Adult Treatment Panel III. hs-CRP was classified into three categories:
      Low < 1 mg x L(-1); intermediate: 1-3 mg x L(-1); and high: > 3 mg x L(-1).
      RESULTS: The prevalence of MS was 14.8%. The hs-CRP level in the population
      studied was 1.68 +/- 1.79 mg x L(-1). hs-CRP significantly increased with age.
      The pilots with MS presented significantly higher hs-CRP levels (median = 1.9
      with an interquartile range (IQR) = 2.5 mg x L(-1)) than the pilots without MS
      (median = 0.9 and IQR = 1.275 mg x L(-1)). MS significantly increased in the
      groups with high hs-CRP in comparison with pilots with intermediate hs-CRP levels
      and with those with low hs-CRP levels. A similar association was found between
      the levels of hs-CRP and the prevalence of MS in the three age groups. The levels
      of hs-CRP increased in pilots as they presented greater numbers of MS diagnostic
      criteria. DISCUSSION: hs-CRP rises significantly in pilots of increasing age, in
      pilots with MS as compared to those without the syndrome, and in pilots as they
      present greater numbers of MS diagnostic criteria. The prevalence of MS increased
      among the groups with higher levels of hs-CRP.

PMID- 22606868
TI  - Common mental disorders among civil aviation pilots.
AB  - INTRODUCTION: The purpose of this study was to estimate the prevalence of
      suspected cases of common mental disorders (CMD) on Brazilian civil aviation
      pilots and to investigate associations between CMD, demographics, and labor
      variables. METHODS: A quantitative cross-sectional study was conducted on 807
      working pilots between October 2009 and October 2010 using a self-administered
      questionnaire to obtain sociodemographic data and information about workload. CMD
      prevalence was estimated with the Self-Reporting Questionnaire-20 items (SRQ-20).
      Multiple logistic regression was used in statistical data analyses. RESULTS: The
      overall prevalence of CMD was 6.7% with the cutoff point of 8 used in this study,
      i.e., scores greater than or equal to 8 in SRQ-20 define positive cases. Using
      alternative cutoffs, the prevalence was 9.2% (cut off point 7) or 12% (cutoff
      point 6). Among the individuals who did not exercise, 10.2% presented suspected
      CMD. Among those with a heavy workload, 23.7% presented scores indicating
      suspected CMD. Only variables relating to workload and the practice of physical
      activity were significantly correlated with the estimate of CMD after
      multivariate analysis. Regular physical exercise afforded a possible protective
      effect against suspected cases of CMD, while there was a higher prevalence of
      suspected cases among subjects with heavy workloads. DISCUSSION: The inclusion of
      the topic of mental health among the targets and priorities of civil aviation in
      Brazil is imperative. Addressing issues such as the regular practice of physical
      activity and workload can contribute to achieving a better balance between flight
      safety and productivity.

PMID- 22606869
TI  - The occupational health and safety of flight attendants.
AB  - In order to perform safety-critical roles in emergency situations, flight
      attendants should meet minimum health standards and not be impaired by factors
      such as fatigue. In addition, the unique occupational and environmental
      characteristics of flight attendant employment may have consequential
      occupational health and safety implications, including radiation exposure,
      cancer, mental ill-health, musculoskeletal injury, reproductive disorders, and
      symptoms from cabin air contamination. The respective roles of governments and
      employers in managing these are controversial. A structured literature review was
      undertaken to identify key themes for promoting a future agenda for flight
      attendant health and safety. Recommendations include breast cancer health
      promotion, implementation of Fatigue Risk Management Systems, standardization of
      data collection on radiation exposure and health outcomes, and more coordinated
      approaches to occupational health and safety risk management. Research is ongoing
      into cabin air contamination incidents, cancer, and fatigue as health and safety
      concerns. Concerns are raised that statutory medical certification for flight
      attendants will not benefit either flight safety or occupational health.

PMID- 22606870
TI  - Gnatho-postural treatment in an air force pilot.
AB  - BACKGROUND: Due to the stresses of flight, air force pilots are more likely to
      experience oral parafunctions such as bruxism when compared to the general
      population. Further, their craniocervical mandibular system is subjected to
      particular stresses in the course of their duties. The aim of this study was to
      analyze an air force pilot who was undergoing gnatho-postural treatment in order
      to protect the masticatory system and achieve better occlusal balance. CASE
      REPORT: A 32-yr-old pilot from the Italian Air Force national aerobatic team
      P.A.N. Frecce Tricolori was chosen from the pilots analyzed and treated at the
      Istituto Medico Legale A. Mosso. A resin stabilization splint was designed for
      the pilot's lower arch, allowing for the unobstructed excursive glides of the
      mandible in the protrusive position, and laterality and occlusal balance in the
      centric position. DISCUSSION: The clinical gnatho-postural treatment involving a
      functional diagnostic instrument used on Italian Air Force pilots protects the
      masticatory system from dental abrasion and, in this particular case, seemed to
      improve the pilot's posture control system as analyzed by the stabilometric
      platform.

PMID- 22606871
TI  - Aeromedical evacuation using an aircraft transit isolator of a patient with Lassa
      fever.
AB  - BACKGROUND: Lassa fever is a viral hemorrhagic fever only present in West Africa.
      The mortality rate is 1% and may reach 15% among hospitalized patients.
      Transmission between humans is mostly due to direct contact with infected body
      fluids. Aeromedical evacuation of patients with viral hemorrhagic fevers (such as
      Lassa fever) demands strict isolation measures. Only a few cases of such
      evacuations have been reported in the literature during the last 40 yr. The use
      of an aircraft transit isolator device could be helpful. CASE REPORT: We report
      the aeromedical evacuation of a confirmed Lassa fever patient from Sierra Leone
      to Sweden with a dedicated air ambulance using an aircraft transit isolator. The
      patient was a 30-yr-old physician working for a nonprofit organization. The
      patient contracted the disease working with infected hospitalized patients. The
      duration of the mission between activation and arrival at the Swedish hospital
      was 36 h, which is within the World Health Organization recommendations.
      DISCUSSION: Evacuation of patients with potentially lethal contagious infections
      is possible, but only with strict isolation measures. Specific protective
      equipment and isolator are mandatory. Medical and technical crews performing such
      evacuations should be trained in proper equipment use and the isolator should
      first be used with a low-risk patient to create minimal risk transport
      conditions.

PMID- 22606872
TI  - Application of exhaled nitric oxide in pulmonary oxygen toxicity.

PMID- 22606873
TI  - Neuroprosthetics.

PMID- 22606875
TI  - This month in aerospace medicine history.

PMID- 22606874
TI  - You're the flight surgeon. Addison's disease.

PMID- 22606876
TI  - [Colonization and transmission of Haemophilus influenzae type b (Hib)].
AB  - Haemophilus influenzae type b (Hib) remains the leading cause of invasive
      bacterial infection in Japanese children. More than 110 countries that have
      included Hib conjugate vaccines in their routine vaccination programs have seen
      dramatical decrease in the incidence of Hib infections. In Japan, the vaccine has
      been introduced for voluntary immunization since December 2008 and has been
      provided free of charge only since January 2011. This review reports the
      prevalence of Hib and its clones among healthy children and pediatric patients
      diagnosed with invasive or non-invasive Hib infections in Sado Island, Japan. Of
      25 Hib isolates collected in this surveillance, 4 genotypic patterns (ST54
      gBLPACR-III, ST54-gBLNAR-I/II, ST190-gBLNAS, and ST95-gBLPACR-I/II) were
      detected. These STs were double or triple-locus variants of each other. Under the
      same antimicrobial selective pressure, high prevalence of gBLPACR strain (76.0%)
      was confirmed in Hib isolates, while gBLPACR prevalence in nontypeable H.
      influenzae was very low (5.2%). These data suggested that each ST strain may be
      brought into Sado Island by different routes. We note that surveillance of
      healthy subjects to identify Hib carriers is important to understand their role
      in transmission of Hib.

PMID- 22606877
TI  - [Prevalence of human metapneumovirus infection in hospital wards handling
      patients with severe motor and intellectual disabilities].
AB  - Epidemics of infectious diseases often occur in hospital wards handling patients
      with severe motor and intellectual disabilities. However, the causative pathogens
      are not identified in half of these epidemics. Recently, an epidemic occurred in
      2 wards consecutively in the National Hospital Organization Ehime Hospital in
      March-April, 2010. In this epidemic, 18 of 40 patients in one ward and 14 of 60
      patients in another ward showed symptoms, and human metapneumovirus (HMPV) was
      detected from pharyngeal and/or nasal swabs of 4 patients. Phylogenetic analysis
      of the viral genomes showed that the virus belonged to subgroup B2, and the same
      virus had spread consecutively in 2 wards. High fever lasted for 5.3 days on
      average in the 32 inpatients, was mostly over 38 degrees C and was accompanied by
      productive coughs. In the 4 patients in whom human HMPV was detected, the number
      of peripheral blood lymphocytes decreased but that of monocytes increased.
      Pneumonia developed in two patients as shown by chest radiography, and an
      increased number of peripheral blood neutrocytes and increased CRP levels were
      noted. Of the 151 inpatients, anti-human HMPV antibody was found in the sera of
      143 (95%), and the relationship between high fever and antibody titer was not
      significant, indicating that HMPV infection could recur in spite of the presence
      of specific antibodies. Because human HMPV is highly prevalent, and causes high
      fever and pneumonia, hospital staff should be vigilant for any signs of this
      virus in hospital wards and take steps to prevent infection in long-term
      inpatients.

PMID- 22606878
TI  - [Usefulness of phage ORF typing, a rapid genotyping method as a molecular and
      epidemiological method for detecting methicillin resistant Staphylococcus
      aureus].
AB  - Surveillance is very important for preventing the nosocomial spread of
      methicillin-resistant Staphylococcus aureus (MRSA), and the pulsed-field gel
      electrophoresis (PFGE) method has long been used to identify the infection source
      and route as a molecular and epidemiological genotyping method. However, the use
      of the method in routine clinical laboratory measurements is difficult due to its
      complicated procedures. Since a molecular and epidemiological genotyping kit
      based on the POT (Phage Open-reading Frames Typing) method has been developed, we
      examined 192 MRSA isolates newly detected from inpatients in our hospital in 2010
      in order to investigate the usefulness of POT for surveying outbreaks of MRSA.
      Among the 192 isolates 118 were suspected of nosocomial spread by the previous
      method, which defined a MRSA detection at more than 48 hours after admission as a
      nosocomial spread. The POT method was introduced at our laboratory in 2010, and
      we were able to recognize 38 patients as having strongly suspected nosocomial
      MRSA infection with the POT method taking into consideration the infection
      situation, such as places (wards and transfer) and time (date of admission and
      date of collected samples). Our Infection Control Division was confidently able
      to demonstrate the current condition of the nosocomial spread by providing the
      results to the clinical staff, who were also able to practice infection control
      confidently. We concluded that the POT method was very useful and convenient for
      investigating MRSA isolates and evaluating collected data because no particular
      analysis other than the digitizing electrophoretic pattern method was necessary.

PMID- 22606879
TI  - [Capsular types, virulence factors and DNA types of Klebsiella oxytoca strains
      isolated from blood and bile].
AB  - Klebsiella oxytoca is an opportunistic pathogen and is isolated at the second
      highest frequency among genus Klebsiella from hospitalized patients. According to
      previous reports, the major virulence factors of K. pneumoniae include capsules
      and several kinds of pill, whereas the virulence factors of K. oxytoca have not
      been well investigated. We noticed an increased frequency of K. oxytoca isolates
      from patients who had undergone a biliary tract operation in a general hospital
      from May through November, 2009. We then performed a PCR analysis of the
      virulence factors and an epidemiological analysis with capsular typing
      (serotyping) and pulsed field gel electrophoresis (PFGE) for K. oxytoca of 11
      blood isolates and 10 bile isolates. As a result, serotypes of K9, K15, K26, K31,
      K43, K47, K55, K70, and K79 were identified in these strains, and K1 and K2 which
      are frequent serotypes in K. pneumoniae strains were not observed. Two blood
      isolates of the K55 serotype showed almost the same PFGE pattern, suggesting that
      these isolates were very closely related and caused cross-infection in a hospital
      ward. Strains of the K43 serotype were three blood isolates and 1 bile isolate,
      all of which showed different PFGE patterns. There were no common isolates among
      the blood and bile isolates. A PCR search revealed that fimH and mrkD genes which
      are relevant to type 1 and type 2 pili, respectively, were present in all
      strains, whereas kfuBC, an iron uptake gene, and cf29a were detected in only a
      few strains. Neither of the mucoid phenotype-related genes magA and rmpA was
      present in any strains. These results strongly suggest that type 1 and/or type 3
      pili would have important roles in the pathogenesis of blood infection and bile
      infection caused by K. oxytoca.

PMID- 22606880
TI  - [Relationship between BCG immunization coverage and the immunization delivery
      system in the Tama area of Tokyo].
AB  - PURPOSE: The BCG immunization has long been performed in Japan. Although the BCG
      immunization service is the responsibility of the municipality, the manner in
      which the BCG immunization is delivered differs from municipality to
      municipality. The purpose of this study was to clarify how the different manner
      of the BCG immunization delivery systems influenced the BCG immunization
      coverage. METHODS: The study of BCG immunization coverage was conducted in the
      Tama area located in the western suburbs of Tokyo in 2004. The birth data and the
      immunization history by the age of 3 years were collected in the three-year-old
      health check-up from a total of 2,341 children residing in the Tama area. Based
      on the age at immunization for each child, the BCG immunization coverage was
      calculated according to the types of the BCG immunization delivery system. The
      immunization types were defined as follows; the BCG immunization given on the
      occasion of the mass health check-up (Group 1); the exclusive mass BCG
      immunization in a monthly service (Group 2); the exclusive mass BCG immunization
      in a bimonthly service (Group 3); the exclusive mass BCG immunization in services
      of fewer than every two months (Group 4); and the immunization given on an
      individual basis by a general practitioner (Group 5). A univariate analysis was
      performed to examine the relationship between the BCG immunization coverage by
      the age of 6 months and the difference among the BCG immunization delivery
      systems, followed by a multivariate regression analysis to adjust for the factors
      related to the demography, health care services and the socio-economic status of
      the municipalities. RESULTS: Unadjusted odds ratios and adjusted odds ratios for
      BCG unimmunized children under the age of 6 months by the BCG immunization
      delivery manner groups were OR 1 reference, adj. OR 1 reference in Group 1; OR
      1.42 CI 0.87-2.29, adj. OR 4.01 CI 2.24-7.11 in Group 2; OR 4.96 CI 3.66-6.82,
      adj. OR 15.59 CI 10.10-24.49 in Group 3;OR 18.60 CI 13.77-25.49, adj. OR 48.17 CI
      29.62-79.75 in Group 4; and OR 4.24 CI 2.86-6.31, adj. OR 15.61 CI 9.05-27.26 in
      Group 5. The univariate analysis and multivariate regression analysis revealed an
      influence of the BCG immunization delivery manner on the BCG immunization
      coverage. CONCLUSION: The choice of BCG immunization delivery manner is very
      important to raise the BCG immunization coverage. The BCG immunization given on
      the occasion of the mass health check-up and the high-frequent immunization
      service are thought to improve the BCG immunization coverage.

PMID- 22606881
TI  - [Toxoplasmic encephalitis in a case of acute myelogenous leukemia after
      conventional consolidation chemotherapy].
AB  - Toxoplasmic encephalitis is a rare complication in patients with hematological
      malignancies. It is infrequently reported in patients undergoing allogeneic
      hematopoietic stem cell transplantation, much less in patients after conventional
      chemotherapy. A 75-year old female with acute myelogenous leukemia had an episode
      of aphasia, right homonymous hemianopsia, and consciousness disturbance 122 days
      after consolidation chemotherapy. Multiple enhancing space occupying lesions
      involving the left occipital lobe were seen on magnetic resonance imaging (MRI).
      HIV antibody was negative. Based on radiological findings, clinical presentation
      and positive Toxoplasma gondii serostatus, sulfadoxine and pyrimethamine were
      added. A rapid improvement was observed thereafter. Heightened awareness of the
      occurrence of toxoplasmic encephalitis, even in non-HIV patients, is needed for a
      better outcome.

PMID- 22606882
TI  - [A case of lung infection complicated by pneumothorax caused by Mycobacterium
      marinum].
AB  - Mycobacterium marinum is a waterborne mycobacterium that commonly infects fish
      and amphibians worldwide, but transmission to humans can occasionally occur,
      typically as a granulomatous skin infection following minor hand trauma.
      Infection involving the lungs is very rare. We herein describe a case of M.
      marinum-associated pneumonia and pneumothorax. In August 2008, an 81-year-old man
      was admitted to a hospital for detailed examination of weight loss and an
      abnormal shadow on chest imaging. Based on a sputum test, nontuberculous
      mycobacteriosis caused by M. marinum was diagnosed. At that time, the blood
      chemistry revealed no respiratory symptoms or inflammatory findings, and the
      patient was treated on an outpatient basis with erythromycin and an expectorant.
      In late November 2008, sputum and coughing were observed. Furthermore, the
      patient developed a fever and chest pain that increased while breathing and he
      visited the emergency outpatient unit of our hospital on December 1. Hypoxemia,
      bilateral pneumonia, and right pneumothorax were observed, and a chest tube was
      inserted into the right thoracic cavity. Results of an acid-fast bacteria smear
      from the sputum and pleural effusion were positive, and M. marinum was identified
      on culture. The patient was diagnosed as having a lung infection complicated by
      pneumothorax caused by M. marinum. The lung infection was ameliorated with
      clarithromycin, rifampicin and ethambutol. However, no decreased in the air
      leaking from the chest tube was noted and inflation of the lung was incomplete.
      The department of respiratory surgery therefore performed thoracoplasty and lung
      cerclage. Subsequently, the air leak subsided, allowing removal of the chest tube
      and the patient was discharged.

PMID- 22606883
TI  - [Environmental control of norovirus shedding in an asymptomatic infant].

PMID- 22606884
TI  - [Utility of immune adherence hemagglutination method for antibody measurement of
      varicella vaccination].

PMID- 22606885
TI  - [Compressive therapy of lymphedema].
AB  - Lymphedema is a simple complication after mastectomy. On current data there are
      two main methods of treatment of this disease that include different physical
      exercises, massage, compression of the edematous tissue and limb bandaging. One
      of this methods is based on the serial compression of the limb with an
      intermittent pump that is followed by physical exercises. Another method is known
      as the complex decongestive therapy (CDP) by Foldi. Individual treatment program
      is worked out for each woman. The positive effect of treatment can be reached
      after a year of strict adherence to the program.

PMID- 22606886
TI  - [Clinical-pathogenetic features of meningococcal infection in children].
AB  - Analysis features of clinical manifestation and pathogenetic mechanisms of
      development of meningococcal infection is introduced. It is emphasized that in
      most cases mentioned infection is characterized by mild course as
      nasopharyngitidis. However relatively seldom developing generalize form put this
      phatology on third place after intestinal infections and septicemia in structure
      of child mortality from infection deseases. Occurence of generalize forms of
      meningococcal infection depend on peculiarity of immune response is followed by
      release of endotoxin and exotoxin in blood stream. This toxins start up
      pathogenetic mechanisms, which lead to toxic shock, adrenal glands hemorrhage,
      brain edema, brain stem wedge in big occipital foramen.

PMID- 22606887
TI  - [Structural and functional changes of myocardium in Chernobyl disaster clean-up
      workers with atrial fibrillation].
AB  - Particularities and clinical importance of the structural and functional changes
      of myocardium were estimated in Chernobyl disaster clean-up workers with atrial
      fibrillation (AF). We examined 122 men with AF, which was associated with
      ischemic heart disease and arterial hypertension. Paroxysmal AF was diagnosed in
      42 patients, 80 patients had permanent AE Control group comprised 80 men without
      AF. Echocardiography and Doppler studies were performed using ultrasound scanner
      Aloka SSD-630 (Japan). Significant structural and functional changes of the heart
      were revealed already in paroxysmal AF and became more pronounced in permanent
      AF. Increased left atrial size, its ratio to left ventricular end diastolic
      diameter, diastolic dysfunction were important echocardiographic predictors of
      AF. Heart walls thickening was accompanied by disorders of myocardial relaxation,
      increase in myocardial mass led to ischemia, and together they promoted overload,
      dysfunction of atrium and development of AF. Obligatory echocardiographic
      examination of the Chernobyl disaster clean-up workers with ischemic heart
      disease and arterial hypertension is necessary for predicting AF early, ordering
      adequate therapy in proper time and improving prognosis.

PMID- 22606888
TI  - [Application BAA "Glucorn" for the correction fatty-acid composition of pulmonary
      surfactant lipids in children-residents of radiation contaminated territories].
AB  - During application of BAA "Glucorn" for the correction of fatty-acid composition
      of pulmonary surfactant lipids in children-residents of radiation contaminated
      territories detected changes, evidence about increasing adaptation-compensatory
      processes in lipid membrane structures of pulmonary surfactant and respiratory
      tracts epithelium, activation of enzymatic pathway conversion of polyunsaturated
      fatty acids in their derivations--eicosanoids in absence the changes lipid
      peroxydation.

PMID- 22606889
TI  - [Modern methods of reflexotherapy in treatment and medical rehabilitation of
      patients with the remote consequences of the closed craniocerebral trauma, which
      tested influence of factors of radioecology catastrophe].
AB  - In the article, which contains the results of own researches the uses over of
      physical factors given about possibility are brought on the different stages of
      rehabilitation patients with the remote consequences of the closed craniocerebral
      trauma, which tested influence of factors of radioecology catastrophe. It is
      underlined that is combined the use nosotropic grounded pharmako-, phsicho-,
      phizio- and reflexotherapy are perspective due to possible their therapeutic
      sinergy at adequate to neat factors and their parameters.

PMID- 22606890
TI  - [Heart rate variability changes in patients with hypertension and its prognostic
      value].
AB  - Hypertension is independent and one of the most important risk factor of
      cardiovascular mortality. 313 patients with I-III stages of hypertension were
      included in study. Assessment of autonomic nerve system activity was done by
      measurement of heart rate variability on the base of rythmogramme according to
      standard methods. Decrease of HRV (till 1175 +/- 1571 ms2, P < 0.01) was observed
      in patients with hypertension. It was associated with presents of main risk
      factors: heart rate, age and gender, stage and severity of disease, decrease of
      LV systolic and diastolic function. Decrease of HRV also associated wit fall of
      parasympatic activity (in 1,7 times, P < 0,05). Autonomic nerve system in patient
      with hypertension try to attain steady stay balance and preserve BP increase
      during orthostatic load. Combination of HRV decrease and LH hypertrophy is
      negative prognostic factor regarding 2-years mortality in patients with
      hypertension.

PMID- 22606891
TI  - [Cerebral aneurysm occlusion in patients with critical vasospasm in acute period
      of disease].
AB  - Aneurismal hemorrhages are often complicated by vasospasm (VS). The
      pharmacological vasodilatation using during endovascular operations allows making
      the occlusion on the peak of vasospasm to prevent the repeated aneurysmal
      rupture. An advantage of the superselective introduction (CI) consists in
      creation of the high concentration of medical substance in the damage segment
      that allows applying biologically highly active preparations, thus reducing their
      general influence on a body. Except pharmacological influence, CI causes
      considerable reflex stimulation of a blood flow owing to the direct irritation of
      sympathetic nervous system angioreceptors. 153 patients with aneurysms were
      operated on a vasospasm peak; CI was applied in 24 cases. The severity of the
      condition defined by WFNS: I - 32 (20,9 %), II - 41 (26,8 %), III - 49 (32 %), IV
      - 30 (19,6 %), V - 1 (0,7 %). All patients were in the acute period of a
      hemorrhage (prior to 21 days). CI was spent in the presence of a critical
      vasospasm (> or = 70 %). Results estimated by a principle of satisfactory
      dilatation (sufficient restoring of a vessel lumen for operating system carrying
      out)--22 (92 %) and unsatisfactory dilatation--2 (8%) cases. Some features were
      found: extension of all capillary network, absence of any ischemic or hemorrhage
      complications, artery expansion in 5-6 min after infusion, dilatation was
      disagreed with a possible physiological artery lumen, extension of all artery,
      instead of a local vassel segment, absence of vasospasm recurrence throughout the
      subsequent 1-1,5 h. Method of the medical substance superselective introduction
      directly in to the constricted artery allows to conduct endovascular occlusion of
      aneurysms on a peak of the critical vasospasm.

PMID- 22606892
TI  - [Pharmacotherapy with fixed low-dose combination of perindopril and the
      indapamide for arterial hypertension].
AB  - The antihypertensive effects and tolerance of a fixed low-dose combination of the
      angiotensin-converting enzyme (ACE) inhibitor perindopril (2 mg) and the diuretic
      indapamide (0.625 mg) were studied in patients with mild and moderate arterial
      hypertension. The patients' mean age was 51.35 +/- 5.02 years. The
      antihypertensive effects were evaluated from the results of daily blood pressure
      monitoring following 12 weeks of therapy. It was found that low-dose combination
      of perindopril and the indapamide exerted a multidirectional corrective effect on
      the daily blood pressure (BP): it provided a significant optimal BP lowering
      during a day on a long-term basis and significantly diminished the baseline
      increased systolic and diastolic BP variability during a day.

PMID- 22606893
TI  - [Clinic laboratory and integrated ultrasonic study in patients with liquid
      formation in diphtheria catamnesis].
AB  - It has been determined that in 9.3% of patients suffered from diphtheria of
      fauces in catamnesis till 10 years cysts of renal sinus were revealed by
      ultrasonic study which should be differentiated with calicopieloectasies. The
      method of pharmocoechography with introducing diuretics is very informative and
      reliable way of differential diagnostics. The cysts of renal sinus have been
      recorded in the indices of the study by ultrasonic study. It has been found that
      in patients suffered from severe diphtheria are in 1.8-2 times higher in
      frequency than in patients with slight and intermediate degree of disease. In
      57.1% of patients with cysts of renal sinus chronic TIN was diagnosed. Frequency
      of cysts of renal sinus in patients with diphtheria exceeds frequency by older
      people in 3-9 times. Patients with renal cysts suffered from diphtheria should be
      under urological control in long-term regular medical check-up and need
      ultrasonic study with pharmocoechography and echodoplerography of renal vessels.

PMID- 22606894
TI  - [Combined treatment of recurrent ovarian cancer using citoreductive surgery and
      intraoperative hypertermical introabdominal hyper fusion].
AB  - This article analyses results of combined treatment of 40 female patients' age 28
      73 (average 55) years with recurrent ovarian cancer who were treated in the Lviv
      state oncologist regional medically-diagnostic center from 2008 to 2010 year,
      using citoreductial interferes and introoperational pyrexias introabdominal hyper
      fusion.

PMID- 22606895
TI  - [Cytogenetic peculiarity of chromosomal abnormalities in myelodisplastic
      syndromes in childhood].
AB  - Cytogenetic investigation results in bone marrow cells of 70 children and
      teenagers from 1 to 18 years with myelodysplastic syndromes (MDS) were presented.
      Between them were 29 girls and 41 boys. According MDS categories were registrated
      refractory anemia (RA), refractory cytopenia with multilineage dysplasia (RCMD)
      and refractory anemia with excess blasts (RAEB) (30, 29 and 11 patients,
      respectively). High spectrum of mosaic clones in bone marrow cells were found: 1)
      normal and near-tetraploidy 2) abnormal and normal, 3) abnormal, near-tetraploidy
      and normal, 4) evolution of clonal chromosomal abnormalities and 5) unrelated
      clones. Normal clone was estimated in 18.6% cases. Karyotype of bone marrow cells
      in MDS were characterized high frequency of unbalanced (85.7%) and near
      tetraploidy clones (45.7%). Between type of structural rearrangements in all
      categories was dominated deletion - 48.6%. Accordingly categories RA, RCMD, RAEB 
      50, 41.4 and 45.4%, respectively. More often in structural rearrangements in MDS
      were involved chromosomes (Chr) 9, 3 and 11, in RA - Chr 9 and 11, in RCMD - Chr
      3, 11, 17 and 10, in RAEB - Chr 3 and 9.

PMID- 22606896
TI  - [Treatment of elderly patients with non-Hodgkin's lymphoma].
AB  - The analysis of the specifics of the flow of Non-Hodgkin's lymphomas in elderly
      patients is presented. Comparative analysis of the treatment efficacy and
      toxicity with schemes CHOP and CNOP in patients is presented.

PMID- 22606897
TI  - [The role of computer tomography in differential diagnostic of incidentalomas
      adrenal glands].
AB  - The possibilities of computer tomography (CT) for differential diagnosis of
      adrenal incidentalomas (AI) were investigated. CT was done for 157 patients with
      AT: 17--with malignant adrenal tumors (MAT) and 70--with benign adrenal tumors
      (BAT) (61--adrenocortical adenoma, 5--cyst, 3--hematoma, 1--myelolipoma). CT-
      main method of topic diagnostic for AI, which allow to make assumption about
      potential malignancy AI in 76.5% patients. Incidentalomas size more than 10,1sm,
      irregular contours, density more +51HU, signs of invasion, lymphadenopathy,
      regional or remote metastasis are the diagnostic criteria for MAT. In 23.5% cases
      with CT impossible to differentiate the malignant nature of AI. 10.0% patients
      with BAT had a false positive results, which slightly limits the diagnostic value
      of CT.

PMID- 22606898
TI  - [Advantages and disadvantages for current diagnostic approaches which is
      determining the basal metabolic rate and energy expenditure in clinical
      practice].
AB  - This article is devoted to the new method for the determination of basal
      metabolism using 13C-bicarbonate breath test compared to the method of Harris
      Benedict in healthy and patients with impaired thyroid function. The problems of
      diagnostic information content, features and advantages of the clinical
      application of 13C-bicarbonate breath test compared to the method of Harris
      Benedict.

PMID- 22606899
TI  - [Efficiency of modern immunoactive preparation cycloferon at coplex therapy of
      the patients with nonalcoholic steatohepatitis combined with irritable bowel
      syndrome].
AB  - The efficiency of modern immunoactive preparation cycloferon at coplex therapy of
      the patients with nonalcoholic steatohepatitis (NASH) combined with irritable
      bowel syndrome (IBS). It was set that before treatment took place devition of
      immune homeostasis such as cellular immunity and serum interferon activity.
      Application of cycloferon provided to regress of clinical symptoms of NASH,
      combined with IBS and normalization of immune indexes.

PMID- 22606900
TI  - [Change of bone tissue in patients with epilepsy].
AB  - By rezultats study found the difference in bone density in patients with epilepsy
      that a long-term (over 3 years) took anticonvulsants and healthy persons of
      similar age and sex (P < 0.01). Less than 50% of patients with epilepsy had
      normal bone density, in 41.2% patients revealed osteopenia, and in 10.1%--had
      pronounced osteoporosis. Understanding and timely diagnosis of metabolic
      disorders associated with the AEP technique allows neurologists to conduct timely
      prevention of osteoporosis in this group of patients, waiting for clinical
      manifestations of violations of bone density.

PMID- 22606901
TI  - [Pleural effusion and splenic abscess].
AB  - Based on literature data the authors demonstrate the complexity of differential
      diagnosis of pleural effusion syndrome (PES). At the same time they emphasize the
      quantitative increase in patients with splenic abscess (SA). The authors give the
      observation of SA, which is complicated by purulent pleurisy and pleural effusion
      syndrome. They accentuate erroneous diagnostic actions.

PMID- 22606902
TI  - [The posibility of usage microwave energy as an alternative method of
      disinfection for silicone impressions in orthopaedic dentistry].
AB  - In this experimental investigation estimated the effect of microwave disinfection
      on the alteration of dimensional stability of silicone impressions and gypsum
      casts poured from them comparing to an invariable parameters of metal die. In
      this article uncovers the main point of origin, spreading and influence according
      to the classical theory of electro-magnetic waves (EMW) as an example was used
      the model M745R Samsung microwave oven. We evaluated possibilities and advantages
      of use the auxiliary plant for flowing regulation of the power of microwave
      radiation that calls "microUndaDent". It was designed, developed and installated
      by us in the department of orthopaedic dentistry.

PMID- 22606904
TI  - [Problems of day care unit development in modern conditions of medical care
      reform].
AB  - Scientific data on the organization of day care unit in Ukraine and abroad has
      been generalized. Future directions of day care unit development in the State
      Institution of Science "Research and Practical Center of Preventive and Clinical
      Medicine" State Administrative Department, as a scientific and practical
      department, has been exposed.

PMID- 22606903
TI  - [Analysis of results of excerpts of generalized parametric indicators of facet
      classification of occupations in medicine, practical, industrial pharmacy,
      cosmetology and major of related occupations introduced to State classifiers
      003:2010].
AB  - A comparative analysis of the content and the list of codified occupations (CO)
      of State classifiers (SC) of occupations SC 003-95 and SC 003:2010 (total 15 000
      positions) is considered. Found that the number of corresponding CO in the SC 003
      95 consist of 906 items including 57 of Vol. 78 "Care of public health", as well
      as in SC 003:2010 - 799 and 59 respectively.

PMID- 22606905
TI  - [Pharmacoeconomic analysis in geriatric clinic].
AB  - Carrying out pharmacoeconomic analysis allows to prove the choice of effective,
      safe and economically preferable medicinal agents for old patients in medical
      institutions that promotes more rational use of budgetary funds and optimize
      medical care for patients of this age.

PMID- 22606906
TI  - [Analysis of motivational orientation of young people for systematic tutoring
      improving sports].
AB  - This article examines the results of core and additional motivation which define
      the content of motivational orientation of young persons in regular classes
      recreational physical culture and sports. To determine the nature and capacity
      building incentive used experimental method of calculating the integral
      coefficient of incentive tension.

PMID- 22606907
TI  - [Modern peculiarities of dynamics and structure of servicemen of Armed Forces of
      Ukraine retiring in transitional period towards professional Army].
AB  - Operational readiness of personnel of Armed Forces of Ukraine was studied in the
      article based on peculiarities of dynamics and structure of retiring of all
      categories of servicemen. It was established that high rates of retiring related
      to specific classes of diseases indicate low health condition of servicemen which
      has a negative impact on their combat readiness and further fitness for military
      service. Priorities of changes in the process of completing of the Armed Forces
      of Ukraine with human resources in the conditions of transformation to
      professional Army, to include optimization of fitness for military service
      criteria, were defined.

PMID- 22606908
TI  - [Outstanding Soviet zoologist and parasitologist E. N. Pavlovsky--the creator of
      the theory of natural foci of disease].
AB  - The article presents information on the outstanding Soviet Zoology and
      Parasitology, Academician of the Academy of Sciences of the USSR Academy of
      Medical Sciences of the USSR, Hero of Socialist Labour, Lieutenant-General of the
      Medical Service E. N. Pavlovsky, the author of more than 1500 scientific papers,
      the founder of scientific school, one of the few scholars the twentieth century,
      approaching the level of scientists and encyclopedists. Considered its
      contribution to the study of natural foci of diseases has promoted the
      development of environmental trends in parasitology.

PMID- 22606909
TI  - Hounsfield Units ranges in CT-scans of bog bodies and mummies.
AB  - Mummification processes, either artificial or natural, preserve the tissues from
      postmortem decay, but change them from their original state. In this study we
      provided the first comprehensive set of Hounsfield Unit (HU) ranges specific for
      tissues mummified under different environmental conditions (peat bog, cold-dry
      and hot-dry environment). We also analyzed the impact of different museal
      preservation techniques on the HU ranges, as e.g. in the Tollund Man and
      Grauballe Man, two bog bodies from Denmark. The HU results for mummies were
      compared with HU results from forensic cases, cremated and inhumated ancient
      human skeletal remains, and fossil animal bones. Knowledge of the typical HU
      range for the different tissues in mummies may help to avoid misinterpretation of
      increased or reduced radiodensity as evidence of paleopathological conditions.
      Finally, we demonstrate the practical benefit of using our re-defined HU ranges
      by showing the improved results of 3D visualization from automatic segmentation
      in an Inca mummy from Mount Llullaillaco.

PMID- 22606910
TI  - The activity ratio of 228Th to 228Ra in bone tissue of recently deceased humans:
      a new dating method in forensic examinations.
AB  - Reliable determination of time since death in human skeletons or single bones
      often is limited by methodically difficulties. Determination of the specific
      activity ratio of natural radionuclides, in particular of 232Th (Thorium), 228Th
      and 228Ra (Radium) seems to be a new appropriate method to calculate the post
      mortem interval. These radionuclides are incorporated by any human being, mainly
      from food. So with an individual's death the uptake of radionuclides ends. But
      the decay of 232Th produces 228Ra and 228Th due to its decay series, whereas
      228Th is continuously built up in the human's bones. Thus, it can be concluded
      that in all deceased humans at different times after death different activity
      ratios of 228Th to 228Ra will develop in bone. According to this fact it should
      be possible to calculate time since death of an individual by first analysing the
      specific activities of 228Th and 228Ra in bones of deceased and then determining
      the 228Th/228Ra activity ratio, which can be assigned to a certain post-mortem
      interval.

PMID- 22606911
TI  - Diversity in auxology: between theory and practice. Proceedings of the 18th
      Aschauer Soiree, 13th November 2010.
AB  - Auxology has developed from mere describing child and adolescent growth into a
      vivid and interdisciplinary research area encompassing human biologists,
      physicians, social scientists, economists and biostatisticians. The meeting
      illustrated the diversity in auxology, with the various social, medical,
      biological and biostatistical aspects in studies on child growth and development.

PMID- 22606912
TI  - Comparison of BMI and percentage of body fat of Indian and German children and
      adolescents.
AB  - Today, serious health problems as overweight and obesity are not just constricted
      to the developed world, but also increase in the developing countries (Prentice
      2006, Ramachandram et al. 2002). Focusing on this issue, BMI and percentage of
      body fat were compared in 2094 schoolchildren from two cross-sectional studies
      from India and Germany investigated in 2008 and 2009. The German children are in
      all age groups significantly taller, whereas the Indian children show higher
      values in BMI (e.g. 12 years: Indian: around 22 kg/m2; German: around 19 kg/m2)
      and in the percentage of body fat (e.g. 12 years: Indian: around 27%; German:
      around 18-20%) in most of the investigated age groups. The Indian children have
      significantly higher BMI between 10 and 13 (boys) respectively 14 years (girls).
      Indian children showed significant higher percentage of body fat between 10 and
      15 years (boys) and between 8 and 16 years (girls). The difference in overweight
      between Indian and German children was strongest at 11 (boys) and 12 (girls)
      years: 70% of the Indian but 20% of the German children were classified as
      overweight. In countries such as India that undergo nutritional transition, a
      rapid increase in obesity and overweight is observed. In contrast to the
      industrialized countries, the risk of overweight in developing countries is
      associated with high socioeconomic status. Other reasons of the rapid increase of
      overweight in the developing countries caused by different environmental or
      genetic factors are discussed.

PMID- 22606913
TI  - Variant in the FTO gene and biomarkers related to health in mature Slovak women.
AB  - The purpose of this study was to investigate whether variant (rs178 17449, G/T)
      in the first intron of the fat mass and obesity-associated gene (FTO) was related
      to different obesity parameters and blood pressure in mature women from Slovakia.
      A total of 419 Slovak women (241 premenopausal and 178 postmenopausal) ranging in
      age from 39 to 65 years were recruited from different parts of Slovakia. The
      subgroups were categorized based on the WHO (1996) criteria. All participants
      gave written informed consent for participation in this study. Anthropometric
      parameters were measured using standard methods. Fat mass was examined by
      bioimpedance and blood pressure was measured in the morning during the medical
      examination. Genomic DNA was extracted from blood or saliva samples by the JET
      QUICK Tissue DNA spine kit. The FTO variant was determined by PCR and restriction
      analysis according to the methodology of Hubacek et al. (2008). The obtained data
      were statistically analyzed by SPSS 17.0 for Windows. The FTO genotype and allele
      frequencies in the entire sample and in subgroups according to their menopausal
      and blood pressure status fell within the Hardy-Weinberg equilibrium. In
      postmenopausal women the FTO (rs178 17449) genotype was significantly associated
      with systolic blood pressure (SBP) (p = 0.024) in the dominant GG/GT vs.TT model
      and with diastolic blood pressure (DBP) (p = 0.030) in the recessive GG vs. GT/TT
      and the additive model (p = 0.043), respectively. In these postmenopausal women
      regression analysis showed a statistically significant effect of age, BMI and FTO
      dominant model on SBP, and of BMI on DBP among the other variables capable of
      inducing blood pressure differences. This study demonstrates that the SNP rs178
      17449 in the FTO gene is associated with systolic and diastolic blood pressure
      but not with BMI and obesity variables, as already replicated in several
      populations throughout the world.

PMID- 22606914
TI  - Occupational physical activity and risk of coronary heart disease among active
      and non-active working-women of North Dakota: a Go Red North Dakota Study.
AB  - Currently less than half of the US adults meet physical activity (PA)
      recommendations, yet many more are sedentary in their occupations. Sedentary
      workers may therefore be at elevated risk for coronary heart disease (CHD).
      Therefore, the objective of the study is to examine the relationship of CHD risk
      with occupational PA (OCPA) and leisure time PA (LTPA) among working-women. The
      10-year CHD risk and relative risk scores were calculated for 642 working-women.
      Self-report questionnaire determined levels of OCPA and LTPA. Biometric data were
      directly collected on all women. No direct relationship for OCPA and 'high risk'
      of CHD was determined. Insufficient LTPA was significantly associated with
      greater prevalence of 'high risk' of CHD. No dose response relationship was
      determined with PA and CHD risk. The odds of being 'high risk' were significantly
      greater for sedentary workers with insufficient LTPA compared to sufficient LTPA.
      The odds for being 'high risk' were similar among moderately active or heavy
      working women completing insufficient LTPA compared to women doing sufficient
      LTPA. For women with sedentary occupations, a sufficient amount of LTPA is
      essential to reduce CHD risk. Women in moderate to heavy working occupations may
      be acquiring adequate amounts of PA to minimize CHD risk.

PMID- 22606915
TI  - Inheritance of dermatoglyphic traits in twins: univariate and bivariate variance
      decomposition analysis.
AB  - Dermatoglyphic traits in a sample of twins were analyzed to estimate the
      resemblance between MZ and DZ twins and to evaluate the mode of inheritance by
      using the maximum likelihood-based Variance decomposition analysis. The additive
      genetic variance component was significant in both sexes for four traits--PII,
      AB_RC, RC_HB, and ATD_L. AB RC and RC_HB had significant sex differences in
      means, whereas PII and ATD_L did not. The results of the Bivariate Variance
      decomposition analysis revealed that PII and RC_HB have a significant correlation
      in both genetic and residual components. Significant correlation in the additive
      genetic variance between AB_RC and ATD_L was observed. The same analysis only for
      the females sub-sample in the three traits RBL, RBR and AB_DIS shows that the
      additive genetic RBR component was significant and the AB_DIS sibling component
      was not significant while others cannot be constrained to zero. The additive
      variance for AB DIS sibling component was not significant. The three components
      additive, sibling and residual were significantly correlated between each pair of
      traits revealed by the Bivariate Variance decomposition analysis.

PMID- 22606916
TI  - Quantitative dermatoglyphic asymmetry: a comparative study between schizophrenic
      patients and control groups of West Bengal, India.
AB  - Quantitative Fluctuating (FA) and Directional asymmetry (DA) of dermatoglyphics
      on digito-palmar complex were analyzed in a group of 111 patients (males: 61,
      females: 50) with schizophrenia (SZ), and compared to an ethnically matched
      phenotypically healthy control (males: 60, females: 60) through MANOVA, ANOVA and
      canonical Discriminant analyses. With few exceptions, asymmetries are higher
      among patients, and this is more prominent in FA than DA. Statistically
      significant differences were observed between patient and control groups,
      especially in males. In both sexes, FA of combined dermatoglyphic traits (e.g.
      total finger ridge count, total palmar pattern ridge count) are found to be a
      strong discriminator between the two groups with a correct classification of over
      83% probability.

PMID- 22606917
TI  - Portuguese migration to the Canary Islands: an analysis based on surnames.
AB  - As a part of a wider analysis of population and genetic exchange between Spain
      and Portugal, the long-term pattern of Portuguese immigration to the Canary
      Islands was studied by means of the frequency of Portuguese surnames. A database
      of 1,995,833 individuals was obtained from the Spanish National Statistics
      Institute (2006). Among the 826 most frequent surnames to appear, 79 surnames of
      Portuguese origin were selected. The distribution of these surnames by
      municipalities and islands, the Fisher index of diversity, and the Lasker inter
      population relationship coefficients R(ij) were considered. These coefficients
      were inter-correlated and correlated with other variables that could have
      influenced the distribution of surnames. From the observed distribution of the
      frequency of surnames, a non-random migration pattern conditioned by economic
      factors was found. The greatest diversity of surnames existed in cane cultivating
      areas after the first arrival of Portuguese immigrants. A later dispersion of
      surnames among islands was correlated with the inter-island geographic distances.
      In some islands the arrival of new immigrants continued due to their strategic
      location within the Canary archipelago. The Canary Islands reveal a high
      frequency and diversity of Portuguese surnames. The results also prove a
      heterogeneous distribution of these surnames throughout the archipelago. In
      contrast to the Portuguese archipelagos, some Canary localities have received
      immigrants continuously because of their economic importance in sugar cane
      cultivation and strategic geographic location on the maritime routes to Africa
      and America.

PMID- 22606918
TI  - Financial conflicts of interest in science.
AB  - This Article proposes a new direction for addressing financial conflicts of
      interest, which plague biomedical research and threaten scientific integrity.
      This Article descriptively states the controversy surrounding financial conflicts
      of interest by explaining how these conflicts arise and the damage that can be
      created as a result. By describing the scientific process, the Article explains
      that changes to the academic environment may allow the public-private interaction
      to proceed, without creating the problems associated with financial conflicts of
      interest. Financial conflicts of interest are created when the profit-seeking
      motive of a private funding source unduly influences an academic scientist's
      primary responsibilities. The problem with financial conflicts of interest has
      grown since the passage of the Bayh-Dole Act in 1980. The cornerstone of current
      policies to address financial conflicts of interest is disclosure, which is
      inadequate and unsatisfying. The analysis herein changes the trajectory of
      current approaches in this area by proposing that an analysis of the underlying
      environment and behavior leading to conflicts of interest must be considered.
      This Article proposes the use of behavioral economics to craft a policy that
      effectively addresses conflicts of interest. To this end, this Article applies
      research from the field of psychology to understand both the environment of
      academic scientists as well as to begin to understand how academic scientists
      make decisions. Drawing on psychology literature, this article proposes that
      academic scientists may experience cognitive dissonance when faced with a
      situation in which a conflict of interest may arise. This helps to understand why
      an academic scientist may make a decision that creates a conflict of interest. In
      addition, this Article utilizes the results of an empirical study conducted by
      myself and a colleague. In this study, we asked faculty at five medical schools
      to respond to an anonymous survey containing hypothetical situations in which a
      conflict may arise. The combination of the psychology literature and our
      empirical study can provide support to the creation of new policies. Policy
      proposals include implementation of default rules, education, and changes to
      academic requirements. Furthermore, this Article considers ways to incentivize
      medical centers to implement effective policies as well as changes to
      intellectual property law.

PMID- 22606919
TI  - Beyond "safe and effective": the role of the federal government in supporting and
      disseminating comparative-effectiveness research.
AB  - Over the past century, medical advancements have resulted in tremendous health
      gains for Americans. Although the federal government has played a prominent role
      in ensuring that new treatments are safe and effective, questions about which
      medical treatments work best under which circumstances have largely remained
      unanswered. Thus, the federal government's recent major investments in
      comparative-effectiveness research have potential to play a significant role in
      helping both patients and health care providers navigate the vast array of
      available treatment options, as well as in improving the quality, efficiency, and
      delivery of health care system-wide. Yet, the controversial nature of the
      government's foray into comparative-effectiveness research also suggests that the
      path toward realizing these goals may be treacherous. This Article describes the
      rationales for federal support of comparative-effectiveness research and
      potential models for that involvement, analyzes the federal government's recent
      investments in the research, and concludes with predictions about the probable
      outcomes of these investments. While increased federal support for comparative
      effectiveness research is unlikely to achieve all of the benefits anticipated by
      its supporters, it is a crucial step toward ensuring that Americans are able to
      take full advantage of the benefits of medical innovation

PMID- 22606920
TI  - Putting together the pieces: recent proposals to fill in the genetic testing
      regulatory puzzle.
AB  - The idea that genetic information is different from other medical information and
      therefore needs special protection has led to a regulatory puzzle where genetic
      testing is currently regulated under three separate schemes. Although genetic
      tests for over 2,000 diseases are available, less than 10% of these tests have
      been reviewed for clinical validity or utility. Recent action by some genetic
      testing companies has prompted the federal government to propose changes to the
      current regulatory scheme. This article discusses the current framework and the
      recent developments before examining some of the concerns and challenges that
      face the implementation of these proposed changes. The author evaluates the
      proposals and competing interests in order to suggest how genetic testing may
      best be regulated to meet the needs of the industry, clinicians, researchers,
      patients, and consumers.

PMID- 22606921
TI  - Options for state and local governments to regulate non-cigarette tobacco
      products.
AB  - Most tobacco control laws were written to address the scourge of smoking-
      particularly smoking cigarettes. As a result, these laws frequently exclude non
      cigarette tobacco products, which are becoming more prevalent on the market.
      These regulatory gaps jeopardize public health by increasing the possibility that
      these products will be used--particularly by minors and young adults. This
      article examines gaps in regulation using five products as case studies:
      dissolvable tobacco products, electronic cigarettes, little cigars, snus, and
      water pipes. In addition, this article presents policy options that state and
      local governments can adopt to regulate these products more effectively,
      including regulations relating to price, flavors, youth access, use in public
      places, point-of-sale warnings, and marketing. Furthermore, this article contains
      extensive discussion of the recently adopted federal Family Smoking Prevention
      and Tobacco Control Act, which both limits and expands the power of state and
      local governments.

PMID- 22606922
TI  - Prescription data mining, medical privacy and the First Amendment: the U.S.
      Supreme Court in Sorrell v. IMS health Inc.
AB  - In 2011, the United States Supreme Court in Sorrell v. IMS Health Inc. struck
      down a Vermont law that would restrict the ability of pharmaceutical companies to
      purchase certain physician-identifiable prescription data without the consent of
      the prescriber. The law's stated purpose was threefold: to protect the privacy of
      medical information, to protect the public health and to contain healthcare costs
      by promoting Vermont's preference in having physicians prescribe more generic
      drugs. The issue before the Supreme Court was whether the Vermont law represented
      a legitimate, common sense regulatory program or a bold attempt to suppress
      commercial speech when the "message" is disfavored by the state. Striking down
      the law, the Supreme Court applied a heightened level of First Amendment scrutiny
      to this commercial transaction and held that the Vermont law was not narrowly
      tailored to protect legitimate privacy interests.

PMID- 22606923
TI  - Can the FDA improve oversight of foreign clinical trials?: Closing the
      information gap and moving towards a globalized regulatory scheme.
AB  - Currently, pharmaceutical companies' utilization of foreign clinical trial data
      is a ubiquitous and indispensable aspect of gaining approval to market drugs in
      the United States. Cost benefits, a larger pool of ready volunteer subjects, and
      greater efficiency in clinical testing are some of the reasons for conducting
      clinical trials overseas. Despite these advantages, lack of proper oversight may
      have serious public health implications regarding the integrity of clinical
      research, ethical treatment of human subjects, and drug safety. Due to the
      expansive global nature of foreign clinical trials, there are concerns with the
      FDA's ability to monitor and regulate these trials. This article examines the
      FDA's oversight of foreign clinical trials and the agency's limitations
      regulating these trials. In addition to looking at steps the FDA is taking to
      address these limitations, the article examines other potential regulatory and
      cooperative actions that can be taken to effectively monitor foreign clinical
      trials and to ensure data integrity and patient safety.

PMID- 22606924
TI  - Method for studying gas composition in the human mastoid cavity by use of laser
      spectroscopy.
AB  - OBJECTIVES: We evaluated a method for gas monitoring in the mastoid cavity using
      tunable diode laser spectroscopy by comparing it to simultaneously obtained
      computed tomographic (CT) scans. METHODS: The presented optical technique
      measures free gases, oxygen (O2), and water vapor (H2O) within human tissue by
      use of low-power diode lasers. Laser light was sent into the tip of the mastoid
      process, and the emerging light at the level of the antrum was captured with a
      detector placed on the skin. The absorption of H2O was used to monitor the probed
      gas volume of the mastoid cavity, and it was compared to the CT scan-measured
      volume. The ratio between O2 absorption and H2O absorption estimated the O2
      content in the mastoid cavity and thus the ventilation. The parameters were
      compared to the grading of mastoid cavities based on the CT scans (n = 31). The
      reproducibility of the technique was investigated by measuring each mastoid
      cavity 4 times. RESULTS: Both O2 and H2O were detected with good reproducibility.
      The H2O absorption and the CT volume correlated (r = 0.69). The average ratio
      between the normalized O2 absorption and the H2O absorption signals was 0.7,
      indicating a lower O2 content than in surrounding air (expected ratio, 1.0),
      which is consistent with previous findings made by invasive techniques. All
      mastoid cavities with radiologic signs of disease were detected. CONCLUSIONS:
      Laser spectroscopy monitoring appears to be a usable tool for noninvasive
      investigations of gas composition in the mastoid cavity, providing important
      clinical information regarding size and ventilation.

PMID- 22606925
TI  - Subepithelial vocal fold infusion: a useful diagnostic and therapeutic technique.
AB  - OBJECTIVES: Preservation of the maximum amount of subepithelial superficial
      lamina propria (SLP) remains an important goal during microlaryngoscopic surgery
      of phonatory mucosa. Volume expansion of the SLP (Reinke's space) with
      subepithelial infusion of saline solution has been widely adopted since its
      introduction in 1991. This technique has evolved so that it is currently used to
      assist with determining the depth of vocal fold disease, defining residual
      pliable SLP, enhancing microsurgical precision, and identifying unrecognized
      disease. The purpose of this investigation was to examine the indications,
      methods, and benefits of subepithelial infusion of saline solution as an adjunct
      technique during phonomicrosurgery. METHODS: In a prospective case series, we
      collected data on 280 consecutive microlaryngoscopy procedures performed over a
      12-month period. Subepithelial infusion of saline solution was included in 178
      procedures. RESULTS: New disease was identified in 20 of the 178 patients (scar
      in 15, sulcus in 4, and a mucosal bridge in 1). The depth of needle placement
      varied depending on the specific disease: 118 of the 178 infusions were done just
      below the epithelial basement membrane, and 60 infusions were performed deeper
      within the SLP, just superficial to the vocal ligament. The infusion technique
      provided surgical assistance in multiple ways, including identifying residual SLP
      (130 patients), defining the SLP-lesion interface (65 patients), lifting scar (60
      patients),providing tension for cordotomy (47 patients), expanding the SLP volume
      to protect against laser damage (45 patients), and providing hydrostatic
      compression of vascular ectasias or varices for photoangiolysis (7 patients). The
      microlaryngoscopy procedures during which infusion was not performed (102 of 280
      procedures) were primarily for nonglottic cancer (46 patients), stenosis (30
      patients), or arytenoid granuloma (13 patients). CONCLUSIONS: Subepithelial
      infusion of the SLP with saline solution is a useful microsurgical adjunct during
      diagnosis and treatment of phonatory mucosal lesions.

PMID- 22606926
TI  - Surgery or botulinum toxin for adductor spasmodic dysphonia: a comparative study.
AB  - OBJECTIVES: Currently, botulinum toxin (Botox) injection is the standard of
      treatment for adductor spasmodic dysphonia (ADSD). We sought to compare the
      outcome of selective laryngeal adductor denervation-reinnervation (SLAD-R)
      surgery for ADSD to that of Botox injections. METHODS: Patient-oriented measures
      (VHI-10) and objective single-blinded gradings of digital voice recordings were
      utilized as outcome measures. The surgical cohort, recruited by retrospective
      patient selection, consisted of 77 patients with a mean follow-up time of 7.54 +/
      2.55 years (range, 2.2 to 14.2 years). The injection cohort, recruited
      prospectively, included 28 patients with a mean follow-up time of 46.37 +/- 5.51
      days (range, 36 to 54 days). RESULTS: As measured by the VHI-10, the surgical
      patients had significantly improved voice handicap outcome scores (mean, 14.4 +/-
      13.6) as compared to the patients who had Botox injection (mean, 26.5 +/- 12.1; p
      = 0.001). Aside from VHI-10 item 2, the surgical group demonstrated significantly
      improved voice-related function on each VHI-10 component (p = 0.01). Within the
      injection subgroup, 88% agreed that Botox successfully treats their ADSD, yet
      only 63% agreed that Botox improves their speech consistently. Within the
      surgical subgroup, 82% would recommend this surgery to others, and 78% agreed
      that their voice was actually better after surgery than after Botox. Objective
      voice ratings demonstrated similar levels of breathiness and overall voice
      quality in the treatment subgroups. CONCLUSIONS: When indicated, the SLAD-R
      surgery for ADSD demonstrates outcomes equal to or superior to those of the
      current standard of Botox injections.

PMID- 22606927
TI  - Correlation of nasal obstruction with nasal cross-sectional area measured by
      computed tomography in patients with nasal septal deviation.
AB  - OBJECTIVES: The objective of the present study was to investigate the
      relationship between the subjective sensation of nasal obstruction and the
      corresponding cross-sectional area for nasal airflow in patients with a deviated
      septum. METHODS: Seventy-one patients with a diagnosis of unilateral nasal
      obstruction due to a deviated nasal septum were evaluated by preoperative
      computed tomography. Anterior anatomic characteristics (the internal nasal valve
      angle and the cross-sectional areas at the external nasal valve, the head of the
      inferior turbinate, and the head of the middle turbinate) and posterior anatomic
      factors (the cross-sectional areas at the openings of the frontal sinus,
      maxillary sinus, and end of the nasal septum) were examined. Associations between
      the computed tomography measurements and the subjective severity of nasal
      obstruction were analyzed with a visual analog scale (VAS). RESULTS: Anterior and
      posterior anatomic characteristics were associated with the subjective severity
      of nasal obstruction. Anterior anatomic factors were related to the VAS scores of
      patients with anterior septal deviation, and posterior anatomic factors were
      related to the VAS scores of patients with posterior septal deviation.
      CONCLUSIONS: This study indicated that the anterior and posterior parts of the
      nasal cavity are both related to nasal obstruction. In some patients, the
      posterior part of the nasal cavity was more important than other locations in
      causing nasal obstruction.

PMID- 22606928
TI  - Quantitative evaluation of facial movement and morphology.
AB  - OBJECTIVES: The aim of our study was to quantitatively analyze facial motion
      kinematics by means of an optoelectronic system. In particular, we defined a set
      of easily recognizable reference points for markerization, and tested the
      applicability of our markerization method for an exhaustive characterization of
      the subjects' facial motion through the definition of some kinematic parameters.
      METHODS: Thirty healthy subjects (mean age, 24.6 +/- 1.0 years; 15 female and 15
      male) participated in the study. A set of markers (diameter, 3 mm) was positioned
      on several reference points of the face, and some parameters were computed for
      the characterization of facial morphology and movement, such as ranges of motion,
      angles, times, and distances. RESULTS: The protocol was tested for inter-rater
      and intra-rater reliability by use of intraclass correlation, of which the
      results were good (between 0.4 and 0.75) to excellent (greater than 0.75). The
      parameters were useful for characterizing the resting position, mimicry, and
      speaking movements, and highlighted some distinctions between men and women in
      facial morphology. CONCLUSIONS: The protocol can be applied to a variety of
      facial movements, including speaking. Future works could address the use of the
      protocol in subjects with disorders and the integrated analysis of kinematic
      parameters and voice spectrography.

PMID- 22606929
TI  - VTMR, a new speech audiometry test with verbal tasks and motor responses.
AB  - OBJECTIVES: The aim of this study was to design a complementary speech audiometry
      test using verbal tasks and motor responses (VTMR) to assess the ability of a
      subject to understand and perform simple motor tasks with 3-dimensional objects,
      to describe its construction, and to show the preliminary results of a pilot
      study on the Italian version of the test. METHODS: The items used in the test
      setting included 1 base, 1 hammer, 1 wooden structure with 4 sticks, and 5 rings
      of different colors and 20 lists with 5 verbal tasks per list. The VTMR test and
      bisyllabic speech audiometry were evaluated in normal-hearing subjects with and
      without cognitive impairment and in subjects with sensorineural hearing loss.
      RESULTS: All normal-hearing subjects without cognitive impairment performed the
      VTMR tasks (100%) correctly at 35 dB sound pressure level. In subjects with
      sensorineural hearing loss, the percentage of correct answers was significantly
      higher for the VTMR test than for bisyllabic speech audiometry above 50 dB sound
      pressure level. This percentage was higher for the VTMR also in normal-hearing
      subjects with poor cognitive skills. CONCLUSIONS: The VTMR might make it easier
      to check patients' ability to understand verbal commands than does traditional
      speech audiometry, in particular in those patients with poor test-taking skills.

PMID- 22606930
TI  - Regeneration of tracheal epithelium using a collagen vitrigel-sponge scaffold
      containing basic fibroblast growth factor.
AB  - OBJECTIVES: Our group has had good results in tracheal mucosal regeneration using
      a collagen vitrigel-sponge scaffold in an animal model. In this study, the
      effectiveness of this scaffold with the application of basic fibroblast growth
      factor (b-FGF) was investigated. METHODS: A collagen vitrigel-sponge scaffold was
      fabricated with simultaneous addition of b-FGF. Three types of collagen vitrigel
      sponge scaffolds were made: no b-FGF, 10 ng of b-FGF, and 100 ng of b-FGF. At 3,
      5, 7, and 14 days after implantation in rats, the tracheas were removed and
      histologically evaluated. The regeneration of mucosal epithelium and the
      subepithelial layer was evaluated. RESULTS: Mucosal epithelium, including
      pseudostratified epithelium and ciliated cells, regenerated earlier in the
      scaffolds when b-FGF was applied than when b-FGF was not applied. Regeneration of
      the subepithelial layer, infiltration of inflammatory cells and fibroblasts, and
      angiogenesis were promoted earlier in the scaffolds with b-FGF application.
      CONCLUSIONS: Our technique for tracheal reconstruction using collagen vitrigel
      sponge scaffolds with b-FGF application affords a feasible approach for
      accelerating the regeneration of the intraluminal surface and subepithelial layer
      of tracheal tissue.

PMID- 22606931
TI  - Tolerability of sialendoscopy under local anesthesia.
AB  - OBJECTIVES: We sought to investigate patients' tolerance of sialendoscopy of the
      parotid and submandibular glands with local anesthesia. METHODS: In a
      retrospective case series of 84 adult patients who underwent sialendoscopy with
      local anesthesia at an academic tertiary referral hospital, we analyzed patients'
      demographic data, American Society of Anesthesiologists (ASA) status score,
      perioperative cardiovascular parameters, and results on a 2-question survey.
      RESULTS: Of the 84 patients, 44 were female and 40 were male (mean age, 48.6
      years). The patients had a mean ASA status score of 1.57. On average, 2.16 mL of
      local anesthetic was used. The mean systolic blood pressure was 137 mm Hg, and
      the mean diastolic blood pressure was 80 mm Hg. The duration of the procedure
      showed a significant correlation with the maximum systolic blood pressure (r =
      0.35; p = 0.001), the mean systolic blood pressure (r = 0.25; p = 0.02), the
      maximum diastolic blood pressure (r = 0.37; p = 0.001), and the mean diastolic
      blood pressure (r = 0.31; p = 0.005). The mean heart rate was 77 beats per
      minute. The majority of patients considered the procedure to be tolerable. In
      this series, the indications for conducting sialendoscopy under general
      anesthesia were procedures of greater invasiveness and complex situations with
      multiple sialolithiases, difficult anatomic preconditions, or a very long
      expected operation time. CONCLUSIONS: Sialendoscopy performed with local
      anesthesia is well tolerated, provided that the patient has a good general health
      status and the operative procedure is not expected to be complex or long-lasting.

PMID- 22606932
TI  - Congenital ossicular chain anomalies associated with a mobile stapes footplate:
      surgical results for 23 ears.
AB  - OBJECTIVES: We describe the audiometric results following surgery in a
      consecutive series of patients with a congenital ossicular middle ear disorder
      that was associated with a mobile stapes footplate. METHODS: We performed a
      retrospective analysis of patient charts from a tertiary referral center. A total
      of 23 patients (23 ears) underwent exploratory tympanotomy and ossicular
      reconstruction between 1986 and 2001. The main outcome measure was the
      audiometric results. RESULTS: Overall, we observed a mean gain in air conduction
      pure tone average of 17 dB (from 47 dB to 30 dB), a sensorineural deterioration
      of 3 dB, and a mean postoperative air-bone gap of 19 dB (mean preoperative air
      bone gap of 38 dB). The air-bone gap closure was 20 dB or less in 15 of the 23
      cases (65%), in agreement with the few results reported in the literature.
      Moreover, the audiometric results remained stable. In the syndromic group, the
      mean gain in air conduction was only 13 dB, which was worse than that observed
      for the nonsyndromic ears. CONCLUSIONS: Surgery for congenital ossicular chain
      anomalies with a concomitant mobile stapes footplate provides positive
      audiometric outcomes. Most ears had some sensorineural impairment (10 to 20 dB),
      which influenced the final hearing level attained after surgery. Preoperative
      assessment is mandatory to search for syndromal diagnoses, which might be
      important for patient counseling and prognosis.

PMID- 22606933
TI  - Cooperativity of peptidoglycan synthases active in bacterial cell elongation.
AB  - Growth of the bacterial cell wall peptidoglycan sacculus requires the co
      ordinated activities of peptidoglycan synthases, hydrolases and cell
      morphogenesis proteins, but the details of these interactions are largely
      unknown. We now show that the Escherichia coli peptidoglycan glycosyltrasferase
      transpeptidase PBP1A interacts with the cell elongation-specific transpeptidase
      PBP2 in vitro and in the cell. Cells lacking PBP1A are thinner and initiate cell
      division later in the cell cycle. PBP1A localizes mainly to the cylindrical wall
      of the cell, supporting its role in cell elongation. Our in vitro peptidoglycan
      synthesis assays provide novel insights into the cooperativity of peptidoglycan
      synthases with different activities. PBP2 stimulates the glycosyltransferase
      activity of PBP1A, and PBP1A and PBP2 cooperate to attach newly synthesized
      peptidoglycan to sacculi. PBP2 has peptidoglycan transpeptidase activity in the
      presence of active PBP1A. Our data also provide a possible explanation for the
      depletion of lipid II precursors in penicillin-treated cells.

PMID- 22606934
TI  - Relationship between ABO blood group and bleeding complications in orally
      anticoagulated patients.

PMID- 22606935
TI  - Genetic divergence and the genetic architecture of complex traits in chromosome
      substitution strains of mice.
AB  - BACKGROUND: The genetic architecture of complex traits strongly influences the
      consequences of inherited mutations, genetic engineering, environmental and
      genetic perturbations, and natural and artificial selection. But because most
      studies are under-powered, the picture of complex traits is often incomplete.
      Chromosome substitution strains (CSSs) are a unique paradigm for these genome
      surveys because they enable statistically independent, powerful tests for the
      phenotypic effects of each chromosome on a uniform inbred genetic background. A
      previous CSS survey in mice and rats revealed many complex trait genes (QTLs),
      large phenotypic effects, extensive epistasis, as well as systems properties such
      as strongly directional phenotypic changes and genetically-determined limits on
      the range of phenotypic variation. However, the unusually close genetic relation
      between the CSS progenitor strains in that study raised questions about the
      impact of genetic divergence: would greater divergence between progenitor
      strains, with the corresponding changes in gene regulation and protein function,
      lead to significantly more distinctive phenotypic features, or alternatively
      would epistasis and systems constraints, which are pervasive in CSSs, limit the
      range of phenotypic variation regardless of the extent of DNA sequence variation?
      RESULTS: We analyzed results for an extensive survey of traits in two new panels
      of CSSs where the donor strains were derived from inbred strains with more
      distant origins and discovered a strong similarity in genetic and systems
      properties among the three CSS panels, regardless of divergence time. CONCLUSION:
      Our results argue that DNA sequence differences between host and donor strains
      did not substantially affect the architecture of complex traits, and suggest
      instead that strong epistasis buffered the phenotypic effects of genetic
      divergence, thereby constraining the range of phenotypic variation.

PMID- 22606936
TI  - Mesoporous submicrometer TiO(2) hollow spheres as scatterers in dye-sensitized
      solar cells.
AB  - Hierarchical submicrometer TiO2 hollow spheres with outer diameter of 300-700 nm
      and shell thickness of 200 nm are synthesized by liquid phase deposition of TiO2
      over carbon microspheres as sacrificial templates. The final TiO2 hollow spheres
      are applied as a scattering layer on top of a transparent nanocrystalline TiO2
      film, serving as the photoanode of a dye-sensitized solar cell (DSC). In addition
      to efficient light scattering, the mesoporous structure of TiO2 hollow spheres
      provides a high surface area, 74 m(2)/g, which allows for higher dye loading.
      This dual functioning suggests that TiO2 hollow spheres may be good replacements
      for conventional TiO2 spheres as scatterers in DSCs. A high efficiency of 8.3% is
      achieved with TiO2 hollow spheres, compared with 6.0% for the electrode with 400
      nm spherical TiO2 scatterers, at identical conditions. 

PMID- 22606937
TI  - alpha,alpha'-N-Boc-substituted bi- and terthiophenes: fluorescent precursors for
      functional materials.
AB  - Fluorescent alpha,alpha'-diamide substituted bi- and terthiophene derivatives
      were prepared by Stille and Suzuki couplings. Their one-pot deprotection and
      coupling with 2-thiophene carboxaldehyde led to stable conjugated azomethines.
      These exhibited electrochromic properties, and they were used to fabricate a
      working electrochromic device.

PMID- 22606938
TI  - Activity-based probe for histidine kinase signaling.
AB  - Bacterial two-component systems (TCSs) are signaling pathways composed of two
      proteins: a histidine kinase (HK) and a response regulator (RR). Upon
      stimulation, the HK autophosphorylates at a conserved histidine. The phosphoryl
      group is subsequently transferred to an aspartate on an RR, eliciting an adaptive
      response, often up- or downregulation of gene expression. TCS signaling controls
      many functions in bacteria, including development, virulence, and antibiotic
      resistance, making the proteins involved in these systems potential therapeutic
      targets. Efficient methods for the profiling of HKs are currently lacking. For
      direct readout of HK activity, we sought to design a probe that enables detection
      of the phosphotransfer event; however, analysis of the phosphohistidine species
      is made difficult by the instability of the P-N bond. We anticipated that use of
      a gamma-thiophosphorylated ATP analogue, which would yield a thiophosphorylated
      histidine intermediate, could overcome this challenge. We determined that the
      fluorophore-conjugated probe, BODIPY-FL-ATPgammaS, labels active HK proteins and
      is competitive for the ATP binding site. This activity-based probe provides a new
      strategy for analysis of TCSs and other HK-mediated processes and will facilitate
      both functional studies and inhibitor identification.

PMID- 22606939
TI  - Defining and assessing evidence for the effectiveness of technical assistance in
      furthering global health.
AB  - In an era when health resources are increasingly constrained, international
      organisations are transitioning from directly managing health services to
      providing technical assistance (TA) to in-country owners of public health
      programmes. We define TA as: 'A dynamic, capacity-building process for designing
      or improving the quality, effectiveness, and efficiency of specific programmes,
      research, services, products, or systems'. TA can build sustainable capacities,
      strengthen health systems and support country ownership. However, our assessment
      of published evaluations found limited evidence for its effectiveness. We
      summarise socio-behavioural theories relevant to TA, review published evaluations
      and describe skills required for TA providers. We explore challenges to providing
      TA including cost effectiveness, knowledge management and sustaining TA systems.
      Lastly, we outline recommendations for structuring global TA systems. Considering
      its important role in global health, more rigorous evaluations of TA efforts
      should be given high priority.

PMID- 22606940
TI  - Health related quality of life assessment in Pakistani paediatric cancer patients
      using PedsQLTM 4.0 generic core scale and PedsQLTM cancer module.
AB  - BACKGROUND: The purpose of the study was to evaluate and compare the HRQOL of
      paediatric cancer in comparison to the healthy children across age groups, using
      PedsQLTM 4.0 Generic Core Scales and the PedsQLTM Cancer Module. METHOD: The
      PedsQLTM 4.0 Generic Core Scales and PedsQL Cancer Module 3.0 were administered
      on 56 children including 26 cancer patients and 30 healthy children while
      employing self and proxy report forms. Furthermore, the results were compared
      with their healthy comparison group. RESULTS: The results indicated a significant
      relationship between HRQOL reports of cancer patients and their parents. However,
      the mean of paediatric cancer patients is significantly lower as compare to their
      healthy comparison group. The mean of proxy report is lower overall on both
      PedsQL and PedsQL cancer module reports. CONCLUSION: Conclusively, overall HRQOL
      of cancer patients was lower than healthy children but it is quite similar to
      their parents' perception. Whereas, the parental mean on PedsQL and PedsQL 3.0
      Cancer Module are significantly low. The study indicated a marked difference
      between cancer patients and healthy children's HRQOL perception and unfortunately
      in country like Pakistan where cancer is on increase, no significant work has yet
      been done to explore this area of research. The present study highlighted the
      need to focus on the particular psychological health services required to serve
      the physically challenged population.

PMID- 22606941
TI  - Whole-bone scaling of the avian pelvic limb.
AB  - Birds form the largest extant group of bipedal animals and occupy a broad range
      of body masses, from grams to hundreds of kilograms. Additionally, birds occupy
      distinct niches of locomotor behaviour, from totally flightless strong runners
      such as the ratites (moa, kiwi, ostrich) to birds that may walk, dabble on water
      or fly. We apply a whole-bone approach to investigate allometric scaling trends
      in the pelvic limb bones (femur, tibiotarsus, tarsometatarsus) from extant and
      recently extinct birds of greatly different size, and compare scaling between
      birds in four locomotor groups; flightless, burst-flying, dabbling and flying. We
      also compare scaling of birds' femoral cross-sectional properties to data
      previously collected from cats. Scaling exponents were not significantly
      different between the different locomotor style groups, but elevations of the
      scaling relationships revealed that dabblers (ducks, geese, swans) have
      particularly short and slender femora compared with other birds of similar body
      mass. In common with cats, but less pronounced in birds, the proximal and distal
      extrema of the bones scaled more strongly than the diaphysis, and in larger birds
      the diaphysis occupied a smaller proportion of bone length than in smaller birds.
      Cats and birds have similar femoral cross-sectional area (CSA) for the same body
      mass, yet birds' bone material is located further from the bone's long axis,
      leading to higher second and polar moments of area and a greater inferred
      resistance to bending and twisting. The discrepancy in the relationship between
      outer diameter to CSA may underlie birds' reputation for having 'light' bones.

PMID- 22606942
TI  - Cerebral microbleeds after use of extracorporeal membrane oxygenation in
      children.
AB  - Cerebral microbleeds (CMB) on gradient-recalled echo (GRE) magnetic resonance
      imaging (MRI) are rarely seen in children, yet have been described following
      vascular procedures in adults. Extracorporeal membrane oxygenation (ECMO) has
      been associated with vascular injury and neurological events in children, but
      there have been no reports to date of GRE MRI findings in children treated with
      ECMO. We reviewed MRI scans for all vascular neurology consultations in children
      treated with ECMO at an academic medical center over a 5-year period. In 6 of 12
      cases, GRE was acquired as others were unstable or had contraindications to MRI.
      All 6 of 6 (100%) GRE cases (mean age 2.1 years, 7 female, 5 male) demonstrated
      CMB. CMB were multiple (>3 lesions), situated in cortical or lobar regions, with
      a striking predominance (5/6 cases) for the right carotid distribution. Other
      than CMB, no cases demonstrated intracranial hemorrhage. CMB may be noted on GRE
      MRI after ECMO and may reflect vascular damage from gaseous emboli.

PMID- 22606944
TI  - An update on the ability of St. John's wort to affect the metabolism of other
      drugs.
AB  - INTRODUCTION: Hypericum perforatum (HP), more commonly known as St. John's wort,
      is a popular medicinal herb used for the treatment of depression. HP affects the
      pharmacokinetics of many drugs by inducing cytochrome P450 (CYP) isozymes, such
      as CYP3A4, CYP2C19, CYP2C9, and the P-glycoprotein (P-gp) transporter. AREAS
      COVERED: This review focuses on drugs that are metabolized by CYP3A4, CYP2C19,
      CYP2C9 and P-gp as their plasma concentrations show the effects of concomitant
      use of HP. For the purpose of this review, all electronic databases such as
      PubMed, Scopus, Google Scholar and Cochrane library were searched to identify in
      vitro, in vivo or human studies about the effects of HP on the metabolism of
      drugs. Data collected were published between 1966 and January 2012. EXPERT
      OPINION: There are a number of drugs whose metabolism is reduced by HP. The
      authors point out that metabolic interactions between HP and drugs are not always
      unfavorable and sometimes have benefits (e.g., reduction of irinotecan toxicity
      and increase in clopidogrel responsiveness). HP does not have a significant
      influence on the kinetics of drugs such as carbamazepine, ibuprofen and
      theophylline. The use of HP preparations is not recommended in people who are
      taking immunosuppressants or cardiovascular drugs. With other medications, it is
      recommended that practitioners should only use HP preparations with a low
      hyperforin content and under careful monitoring. It is also recommended that
      because of the reduction in the bioavailability of oral contraceptives
      administered concurrently with HP, women who use HP preparations should use
      additional preventive methods to avoid unintended pregnancy.

PMID- 22606947
TI  - A dielectric model of self-assembled monolayer interfaces by capacitive
      spectroscopy.
AB  - The presence of self-assembled monolayers at an electrode introduces capacitance
      and resistance contributions that can profoundly affect subsequently observed
      electronic characteristics. Despite the impact of this on any voltammetry, these
      contributions are not directly resolvable with any clarity by standard
      electrochemical means. A capacitive analysis of such interfaces (by capacitance
      spectroscopy), introduced here, enables a clean mapping of these features and
      additionally presents a means of studying layer polarizability and Cole-Cole
      relaxation effects. The resolved resistive term contributes directly to an
      intrinsic monolayer uncompensated resistance that has a linear dependence on the
      layer thickness. The dielectric model proposed is fully aligned with the classic
      Helmholtz plate capacitor model and additionally explains the inherently
      associated resistive features of molecular films.

PMID- 22606945
TI  - In vitro anticancer activity of cis-diammineplatinum(II) complexes with beta
      diketonate leaving group ligands.
AB  - Five cationic platinum(II) complexes of general formula, [Pt(NH(3))(2)(beta
      diketonate)]X are reported, where X is a noncoordinating anion and beta
      diketonate = acetylacetonate (acac), 1,1,1,-trifluoroacetylacetonate (tfac),
      benzoylacetonate (bzac), 4,4,4-trifluorobenzoylacetonate (tfbz), or
      dibenzoylmethide (dbm), corresponding, respectively, to complexes 1-5. The log P
      values and the stabilities of 1-5 in aqueous solution were evaluated. The phenyl
      ring substituents of 3-5 increase the lipophilicity of the resulting complexes,
      whereas the trifluoromethyl groups of 2 and 4 decrease the stability of the
      complexes in aqueous solution. The uptake of 1-5 in HeLa cells increases as the
      lipophilicity of the investigated complex increases. Cancer cell cytotoxicity
      studies indicate that 1 and 3 are the least active complexes whereas 2, 4, and 5
      are comparable in activity to cisplatin.

PMID- 22606948
TI  - An evaluation of restaurant noise levels and contributing factors.

PMID- 22606949
TI  - In vivo validation of the unified BARGE method to assess the bioaccessibility of
      arsenic, antimony, cadmium, and lead in soils.
AB  - The relative bioavailability of arsenic, antimony, cadmium, and lead for the
      ingestion pathway was measured in 16 soils contaminated by either smelting or
      mining activities using a juvenile swine model. The soils contained 18 to 25,000
      mg kg(-1) As, 18 to 60,000 mg kg(-1) Sb, 20 to 184 mg kg(-1) Cd, and 1460 to
      40,214 mg kg(-1) Pb. The bioavailability in the soils was measured in kidney,
      liver, bone, and urine relative to soluble salts of the four elements. The
      variety of soil types, the total concentrations of the elements, and the range of
      bioavailabilities found were considered to be suitable for calibrating the in
      vitro Unified BARGE bioaccessibility method. The bioaccessibility test has been
      developed by the BioAccessibility Research Group of Europe (BARGE) and is known
      as the Unified BARGE Method (UBM). The study looked at four end points from the
      in vivo measurements and two compartments in the in vitro study ("stomach" and
      "stomach and intestine"). Using benchmark criteria for assessing the "fitness for
      purpose" of the UBM bioaccessibility data to act as an analogue for
      bioavailability in risk assessment, the study shows that the UBM met criteria on
      repeatability (median relative standard deviation value <10%) and the regression
      statistics (slope 0.8 to 1.2 and r-square > 0.6) for As, Cd, and Pb. The data
      suggest a small bias in the UBM relative bioaccessibility of As and Pb compared
      to the relative bioavailability measurements of 3% and 5% respectively. Sb did
      not meet the criteria due to the small range of bioaccessibility values found in
      the samples.

PMID- 22606950
TI  - Suspected lead toxicosis in an electric eel, Electrophorus electricus (L.).

PMID- 22606951
TI  - Predictors of mortality among HIV infected patients taking antiretroviral
      treatment in Ethiopia: a retrospective cohort study.
AB  - BACKGROUND: Studies indicate that there is high early mortality among patients
      starting antiretroviral treatment in sub-Saharan Africa. However, there is
      paucity of evidence on long term survival of patients on anti-retroviral
      treatment in the region. The objective of this study is to examine mortality and
      its predictors among a cohort of HIV infected patients on anti-retroviral
      treatment retrospectively followed for five years. METHODS: A retrospective
      cohort study was conducted among HIV infected patients on ART in eastern
      Ethiopia. Cox regression and Kaplan-Meier analyses were performed to investigate
      factors that influence time to death and survival over time. RESULT: A total of
      1540 study participants were included in the study. From the registered patients
      in the cohort, the outcome of patients as active, deceased, lost to follow up and
      transfer out was 1005 (67.2%), 86 (5.9%), 210 (14.0%) and 192 (12.8%)
      respectively. The overall mortality rate provides an incidence density of 2.03
      deaths per 100 person years (95% CI 1.64 - 2.50). Out of a total of 86 deaths
      over 60 month period; 63 (73.3%) died during the first 12 months, 10 (11.6%)
      during the second year, and 10 (11.6%) in the third year of follow up. In
      multivariate analysis, the independent predictors for mortality were loss of more
      10% weight loss, bedridden functional status at baseline, <= 200 CD4 cell
      count/ml, and advanced WHO stage patients. CONCLUSION: A lower level of mortality
      was detected among the cohort of patients on antiretroviral treatment in eastern
      Ethiopia. Previous history of weight loss, bedridden functional status at
      baseline, low CD4 cell count and advanced WHO status patients had a higher risk
      of death. Early initiation of ART, provision of nutritional support and
      strengthening of the food by prescription initiative, and counseling of patients
      for early presentation to treatment is recommended.

PMID- 22606952
TI  - Active site binding and catalytic role of bicarbonate in 1,4-dihydroxy-2
      naphthoyl coenzyme A synthases from vitamin K biosynthetic pathways.
AB  - 1,4-Dihydroxy-2-naphthoyl coenzyme A (DHNA-CoA) synthase, or MenB, catalyzes a
      carbon-carbon bond formation reaction in the biosynthesis of both vitamin K1 and
      K2. Bicarbonate is crucial to the activity of a large subset of its orthologues
      but lacks a clearly defined structural and mechanistic role. Here we determine
      the crystal structure of the holoenzymes from Escherichia coli at 2.30 A and
      Synechocystis sp. PCC6803 at 2.04 A, in which the bicarbonate cofactor is bound
      to the enzyme active site at a position equivalent to that of the side chain
      carboxylate of an aspartate residue conserved among bicarbonate-insensitive DHNA
      CoA synthases. Binding of the planar anion involves both nonspecific
      electrostatic attraction and specific hydrogen bonding and hydrophobic
      interactions. In the absence of bicarbonate, the anion binding site is occupied
      by a chloride ion or nitrate, an inhibitor directly competing with bicarbonate.
      These results provide a solid structural basis for the bicarbonate dependence of
      the enzymatic activity of type I DHNA-CoA synthases. The unique location of the
      bicarbonate ion in relation to the expected position of the substrate alpha
      proton in the enzyme's active site suggests a critical catalytic role for the
      anionic cofactor as a catalytic base in enolate formation.

PMID- 22606953
TI  - Meanderings into the regulation of effector class by the immune system:
      derivation of the trauma model.
AB  - The pathway of immune system behaviour can be divided into three modules, each
      with its own logic and database. The modules are related in that they feed
      sequentially into each other for function. The modules are (1) the generation of
      the recognitive repertoire; (2) the sorting of the repertoire by purging it of
      anti-self; and (3) the coupling of the residue, anti-nonself, appropriately to
      the biodestructive and ridding effector functions. While both the generation and
      sorting of the repertoire have been intensively investigated and are well
      understood in terms of firm theoretical frameworks, the understanding of Module
      3, the regulation of effector class, is patchy. This essay is an attempt to
      define the elements required for an understanding of Module 3 and that leads us
      to propose the Trauma Model.

PMID- 22606955
TI  - Cold-surface photochemistry of primary and tertiary alkyl nitrites.
AB  - Reflection-absorption infrared spectroscopy (RAIRS) is used to explore the
      photochemistry of primary and tertiary alkyl nitrites deposited on a gold
      surface. The primary alkyl nitrites examined for this study were n-butyl,
      isobutyl, and isopentyl nitrite. These compounds showed qualitatively similar
      spectra to those observed in previous condensed-phase measurements. The
      photolysis of the primary nitrites involved the initial formation of an alkoxy
      radical and NO, followed by production of nitroxyl (HNO) and an aldehydic
      species. In addition, the formation of nitrous oxide, identified from its
      distinctive transition near 2230 cm(-1), was observed to form from the self
      reaction of nitroxyl. The reaction rates for cis and trans conformer decay, as
      tracked through their intense N?O stretching modes, were found to be
      significantly different, potentially due to a structural bias that favors HNO
      formation for the initial trans conformer photoproducts over recombination. Tert
      butyl nitrite demonstrates only the trans conformer in the RAIRS spectra prior to
      photolysis; however, recombination of the initial NO and RO(*) photoproducts was
      observed to produce the cis conformer in the photolyzed samples. The primary
      photoproducts from tert-butyl nitrite can also react to form acetone and
      nitrosomethane, but the absence of HNO prohibits the formation of N(2)O that was
      observed for the primary alkyl nitrites. Additionally, the RAIRS spectrum of
      isobutyl nitrite co-deposited with water was measured to examine the photolysis
      of this species on a water-ice surface. No change in the identity of the
      photoproducts was observed in this experiment, and minimal frequency shifting (1
      3 cm(-1)) of the vibrational modes occurred. In addition to being a known
      atmospheric source of NO and various aldehydes, our results point to cold surface
      processing of alkyl nitrites as a potential environmental source of nitrous
      oxide.

PMID- 22606954
TI  - Hepatitis B assays in serum, plasma and whole blood on filter paper.
AB  - BACKGROUND: Screening and determining the immune status of individuals for
      hepatitis B is usually done by detecting hepatitis B surface antigen (HBsAg) and
      hepatitis B surface antigen-specific antibodies (HBsAb). In some countries with
      the highest viral burden, performing these assays is currently impractical. This
      paper explores the use of filter paper as a blood specimen transport medium.
      METHODS: Samples, chosen from routine clinical laboratory pool, were applied and
      dried onto filter paper. Eluates, from the paper samples, were analyzed as
      routine clinical specimens on ADVIA Centaur 5634(r) immunoassay analyzers using
      the standard HBsAg and HBsAb kits. Dried blood samples were subjected to a range
      of environmental conditions in order to assess stability. RESULTS: After drying
      and elution the assays showed linearity and precision comparable to clinical
      assays performed on fresh serum. Elutions at various times during a 149 day
      incubation period showed very little variability in the Index numbers. All
      analytes were temperature stable except for a decrease in the HBsAg signal at 42
      degrees C. CONCLUSIONS: Filter paper is an acceptable storage and transport
      medium for serum to be used in the detection of hepatitis B markers if
      atmospheric variability can be controlled. HBsAg, HBsAb and HBcAb are all stable
      for at least five months under storage conditions below room temperature. Drying
      specimens, particularly serum, on filter paper at remote locations, offers a
      reasonable solution to the problem of hepatitis surveillance in underdeveloped
      regions, although some attempt at temperature control might be desirable.

PMID- 22606956
TI  - Future treatment for BPD.

PMID- 22606957
TI  - Autosomal recessive chronic granulomatous disease presenting with cutaneous
      dermatoses and ocular infection.
AB  - Dermatoses such as eczematous dermatitis and cutaneous infection are recognized
      presentations of primary immunodeficiency (PID). However, atopic dermatitis
      affects approximately 10% of infants, and cutaneous infections are not uncommon
      in children, therefore the challenge for the dermatologist is to distinguish the
      few patients that have PID from the many that do not. We report on a 6-year-old
      girl who was ultimately diagnosed with autosomal recessive chronic granulomatous
      disease (AR-CGD) after presenting to various hospitals with dermatitis, scalp
      plaques recalcitrant to treatment, and recurrent infections over a 3-year period,
      and describe some aspects of her diagnosis and management. This report highlights
      the importance of considering rare disorders such as AR-CGD in the differential
      diagnosis of recurrent or recalcitrant dermatological infections in children.

PMID- 22606958
TI  - Effect of norcantharidin on the human breast cancer Bcap-37 cells.
AB  - Norcantharidin (NCTD), a chemically modified form of cantharidin, is a potential
      anticancer drug. In this study, the effects of NCTD on the cellular viability,
      reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and DNA
      damage in the human breast cancer cell line Bcap-37 were investigated with
      confocal and fluorescence microscopy. The cell cycle was further analyzed using
      the CellQuest software of a Becton-Dickinson FACS flow cytometer. The results
      indicated that the cellular viability was decreased with the growing
      concentrations of NCTD and time exposure. Moreover, the fluorescence intensity of
      ROS was increased, whereas the MMP was decreased in Bcap-37 cells with the
      growing concentrations of NCTD. NCTD induced a dose-dependent DNA damage and
      reduced the G1 peak in Bcap-37 cells. The G2/M peak of Bcap-37 was also decreased
      by the higher concentration of NCTD.

PMID- 22606959
TI  - The fruit fly Drosophila melanogaster unfolds the secrets of innate immunity.
AB  - In 2011, the Nobel Prize in Physiology and Medicine was rewarded, in part, for
      research on the Drosophila immune response. The research described the role of
      the Drosophila Toll receptor in antifungal resistance, and the subsequent
      characterization of Toll-like receptors in mammals reshaped our understanding of
      the immune system. This review summarizes the potential of the Drosophila model
      and describes the path that has lead Drosophila to become an important model to
      study immunity. CONCLUSION: Drosophila melanogaster has been one of the most
      fruitful models to study innate immunity.

PMID- 22606960
TI  - A segmental evaluation of arterial stiffness before and after prolonged strenuous
      exercise.
AB  - We aimed to investigate the effects of a single session of prolonged strenuous
      exercise (PSE) on arterial stiffness by measuring pulse wave velocity (PWV)
      before and after competition in an ultramarathon. A total of 20 routine
      ultramarathon competitors (UM) completed baseline and postrace evaluation of
      central PWV (cPWV), upper-limb PWV (uPWV), and lower-limb PWV (lPWV) using
      carotid artery - femoral artery, carotid artery - finger, and femoral artery -
      toe segments, respectively. Fourteen additional age- and gender-matched normally
      active participants (NA) took part in the identical baseline evaluation but did
      not participate in the race. Average ultramarathon completion time was 30 h 47
      min. Mean arterial blood pressure was reduced after exercise (before exercise
      (pre), 92 +/- 7 mm Hg; after exercise (post), 84 +/- 7 mm Hg; P < 0.001), whereas
      heart rate was increased (pre, 57 +/- 10 beats.min(-1); post, 73 +/- 12
      beats.min(-1); P < 0.001). Also, lPWV (pre, 11.8 +/- 3.6 m.s(-1); post, 9.6 +/-
      2.6 m.s(-1); P < 0.05) and uPWV (pre, 5.0 +/- 0.53 m.s(-1); post, 4.4 +/- 0.8
      m.s(-1); P < 0.01) were reduced after exercise. No change in cPWV occurred (pre,
      4.1 +/- 0.8 m.s(-1); post, 3.9 +/- 1.3 m.s(-1); P = 0.55). At baseline, the NA
      group had significantly increased cPWV in comparison with the UM group (UM, 4.1
      +/- 0.8 m.s(-1); NA, 7.4 +/- 1.3 m.s(-1); P < 0.001). Acute participation in PSE
      influenced peripheral but not central arterial stiffness. Those who routinely
      participate in PSE have reduced central arterial stiffness as compared with
      normally active, age- and gender-matched controls.

PMID- 22606961
TI  - Removal of the stylet from the tracheal tube: effect of lubrication.
AB  - We compared the work needed to retract a non-lubricated and a lubricated stylet
      from a tracheal tube over 24 h. Stylets were lubricated with sterile water,
      silicone fluid, lidocaine spray, lidocaine gel, MedPro((r)) lubricating gel or
      Lacri-Lube((r)). The mean (SD) work in joules needed to retract the stylet by 5
      cm from the tracheal tube was recorded immediately (time 0), at 5 and 30 min and
      at 1, 3 and 24 h. At time 0 lubrication with sterile water (0.53 (0.09); p =
      0.001), silicone fluid (0.43 (0.10); p < 0.001), lidocaine gel (0.60 (0.15); p =
      0.01) and MedPro gel (0.57 (0.07); p = 0.005), were better than no lubrication
      (0.94 (0.28)). Where a tracheal tube is pre-loaded with a stylet for use at an
      indeterminate time, silicone fluid was the best choice of lubricant as it
      performed consistently well up to 24 h. At 24 h only silicone fluid (0.49 (0.01))
      outperformed no lubrication (0.77 (0.24); p = 0.04).

PMID- 22606962
TI  - Characterization of Shigella sonnei in Malaysia, an increasingly prevalent
      etiologic agent of local shigellosis cases.
AB  - BACKGROUND: Shigellosis is a major public health concern worldwide, especially in
      developing countries. It is an acute intestinal infection caused by bacteria of
      the genus Shigella, with a minimum infective dose as low as 10-100 bacterial
      cells. Increasing prevalence of Shigella sonnei as the etiologic agent of
      shigellosis in Malaysia has been reported. As there is limited information on the
      genetic background of S. sonnei in Malaysia, this study aimed to characterize
      Malaysian S. sonnei and to evaluate the prospect of using multilocus variable
      number tandem-repeat (VNTR) analysis (MLVA) for subtyping of local S. sonnei.
      METHODS: Forty non-repeat clinical strains of S. sonnei isolated during the years
      1997-2000, and 2007-2009 were studied. The strains were isolated from stools of
      patients in different hospitals from different regions in Malaysia. These
      epidemiologically unrelated strains were characterized using biotyping,
      antimicrobial susceptibility testing, pulsed-field gel electrophoresis (PFGE) and
      MLVA. RESULTS: The two biotypes identified in this study were biotype a (n = 29,
      73%) and biotype g (n = 11, 27%). All the 40 strains were sensitive to kanamycin,
      ceftriaxone and ciprofloxacin. Highest resistance rate was observed for
      streptomycin (67.5%), followed by tetracycline (40%) and trimethoprim
      sulfamethoxazole (37.5%). All the S. sonnei biotype g strains had a core
      resistance type of streptomycin - trimethoprim-sulfamethoxazole - tetracycline
      whereas the 29 biotype a strains were subtyped into eight resistotypes. All the
      strains were equally distinguishable by PFGE and MLVA. Overall, PFGE analysis
      indicated that S. sonnei biotype a strains were genetically more diverse than
      biotype g strains. Cluster analysis by MLVA was better in grouping the strains
      according to biotypes, was reflective of the epidemiological information and was
      equally discriminative as PFGE. CONCLUSIONS: The S. sonnei strains circulating in
      Malaysia throughout the period studied were derived from different clones given
      their heterogeneous nature. MLVA based on seven selected VNTR loci was rapid,
      reproducible and highly discriminative and therefore may complement PFGE for
      routine subtyping of S. sonnei.

PMID- 22606964
TI  - Therapy of severe atopic dermatitis in adults.
AB  - Severe atopic dermatitis has a profound effect on many aspects of the patient's
      life, and a combination of topical and systemic treatment is often necessary to
      control the disease. Systemic corticosteroids are rapidly effective, but should
      only be used short term for severe exacerbations because of their many long-term
      side effects. In chronic cases, starting another systemic immunosuppressant
      therapy while tapering off corticosteroids should be considered. The usefulness
      of cyclosporin A, azathioprine, and methotrexate has been documented in clinical
      trials. Cyclosporin A is rapidly effective, but has a narrow therapeutic index
      and possible renal toxicity. Azathioprine and methotrexate have a slower onset of
      action and are good treatment options for many patients, but are not always
      tolerated. Mycophenolate mofetil, mycophenolate sodium and biologicals are other
      alternatives, but need to be assessed in larger randomized trials. Despite the
      available therapeutic repertoire, there remain patients with very severe disease
      in whom we are unable to obtain satisfactory control. The therapy for patients
      with severe psoriasis has been revolutionized during the last decade, due to the
      development of targeted biological therapy, and it is indeed the hope that a
      similar process is about to emerge also for patients suffering from severe atopic
      dermatitis.

PMID- 22606966
TI  - Neonatal lupus erythematosus and its clinical variability.
AB  - Neonatal lupus erythematosus (NLE) is a rare disease affecting newborns that is
      caused by maternal autoantibodies transmitted across the placenta. The disease
      may affect the skin, the heart, and rarely the hepatobiliary or hematological
      systems. A serious complication affecting some patients with NLE is
      atrioventricular heart block (AV block). The clinical picture of cutaneous NLE
      varies considerably. NLE presents with confluent, scaly, periorbital erythema, or
      erythematous infiltrated plaques with central vesicles and lesions resembling
      seborrheic eczema or fungal infection. In any newborn with such skin lesions, NLE
      should be included in the differential diagnosis. Dermatologists play an
      important role in the diagnosis. We review different skin lesions occurring in
      neonatal lupus erythematosus based on five patients from our own clinic.

PMID- 22606970
TI  - Discovery of a nitric oxide responsive quorum sensing circuit in Vibrio harveyi.
AB  - Bacteria use small molecules to assess the density and identity of nearby
      organisms and formulate a response. This process, called quorum sensing (QS),
      commonly regulates bioluminescence, biofilm formation, and virulence. Vibrio
      harveyi have three described QS circuits. Each involves the synthesis of a
      molecule that regulates phosphorylation of its cognate receptor kinase. Each
      receptor exchanges phosphate with a common phosphorelay protein, LuxU, which
      ultimately regulates bioluminescence. Here, we show that another small molecule,
      nitric oxide (NO), participates in QS through LuxU. V. harveyi display a NO
      concentration-dependent increase in bioluminescence that is regulated by an hnoX
      gene. We demonstrate that H-NOX is a NO sensor and NO/H-NOX regulates
      phosphorylation of a kinase that transfers phosphate to LuxU. This study reveals
      the discovery of a fourth QS pathway in V. harveyi and suggests that bacteria use
      QS to integrate not only the density of bacteria but also other diverse
      information about their environment into decisions about gene expression.

PMID- 22606971
TI  - Strategies for maintaining fitness and performance during Ramadan.
AB  - The Muslim athlete, whether living in a Muslim majority country or in a non
      Muslim country, face unique challenges to faithfully follow one of the pillars of
      their faith - Ramadan - while attempting to maintain their participation in
      sports training and competition. There are conflicting reports on the effects of
      Ramadan on fitness and physical performance in general and in football in
      particular. In general, the impact of a brief daytime fast has minor effects on
      health or factors of physical fitness. Add physical training and now a new set of
      barriers to both performance and the observance of Ramadan begin to interact.
      Practising athletes have worked out strategies to cope with the rigors of
      Ramadan; strategies that have both physical (training modifications, dietary
      habits, rest and recovery) and emotional (patience, emotional preparations)
      domains. Carefully blending strategies like these can help the football player be
      true to their faith and follow the tenants of Ramadan hopefully, with a minimum
      of impact on their physical performance. In this context, science can help
      coaches improve their training plans and educate players with respect to the
      challenges presented by Ramadan to all levels of sports participation.

PMID- 22606972
TI  - Extending limits of chlorine kinetic isotope effects.
AB  - Chlorine kinetic isotope effects exceeding semiclassical limits were observed in
      enzyme-catalyzed reactions, but their source has not been yet identified. Herein
      we show that unusually large chlorine kinetic isotope effects are associated with
      reactions in which chlorine is the central atom that is being passed between two
      heavy atoms. The origin of these large values is the ratio of imaginary
      frequencies for light-to-heavy species (the so-called temperature-independent
      factor).

PMID- 22606973
TI  - Conversion of a dodecahedral protein capsid into pentamers via minimal point
      mutations.
AB  - Protein self-assembly relies upon the formation of stabilizing noncovalent
      interactions across subunit interfaces. Identifying the determinants of self
      assembly is crucial for understanding structure-function relationships in
      symmetric protein complexes and for engineering responsive nanoscale
      architectures for applications in medicine and biotechnology. Lumazine synthases
      (LS's) comprise a protein family that forms diverse quaternary structures,
      including pentamers and 60-subunit dodecahedral capsids. To improve our
      understanding of the basis for this difference in assembly, we attempted to
      convert the capsid-forming LS from Aquifex aeolicus (AaLS) into pentamers through
      a small number of rationally designed amino acid substitutions. Our mutations
      targeted side chains at ionic (R40), hydrogen bonding (H41), and hydrophobic
      (L121 and I125) interaction sites along the interfaces between pentamers. We
      found that substitutions at two or three of these positions could reliably
      generate pentameric variants of AaLS. Biophysical characterization indicates that
      this quaternary structure change is not accompanied by substantial changes in
      secondary or tertiary structure. Interestingly, previous homology-based studies
      of the assembly determinants in LS's had identified only one of these four
      positions. The ability to control assembly state in protein capsids such as AaLS
      could aid efforts in the development of new systems for drug delivery,
      biocatalysis, or materials synthesis.

PMID- 22606974
TI  - Effects of IL-1 receptor-associated kinase-4 gene silencing on human osteoblast
      like cells.
AB  - The aim of this study is to identify the effects of interleukin-1 receptor
      associated kinase-4 (IRAK-4) gene silencing on human osteoblast-like cells. The
      siRNA sequences of the target gene, IRAK-4, were constructed and transferred into
      MG63 cells (control group = MG63 cells; SC group = MG63 cells transfected with
      scrambled IRAK-4 siRNA; KD group = MG63 cells transfected with 75 nM IRAK-4
      siRNA). The morphological changes, cell growth, cell-cycle progression,
      apoptosis, and the expression of various cytokines and proteins were compared.
      Compared with the control and SC groups, IRAK-4 gene silencing in MG63 cells
      caused morphological changes, inhibited growth, altered the cell-cycle
      distribution, increased apoptosis (p < 0.05), decreased bone alkaline phosphatase
      and osteocalcin levels (p < 0.05), and decreased protein expression of Bcl-2/Bax
      and Bcl-2, p-JNK1/2, p-ERK1/2, and p-p38MAPK (p < 0.05). The results indicated
      that IRAK-4 gene silencing in MG63 cells inhibited cell proliferation and
      function and increase apoptosis, which may be related to the decreased Bcl-2/Bax
      ratio and inhibition of the protein expression of various components of the
      mitogen-activated protein kinase pathways. The results of this study may help
      improve the understanding of the relationship between IRAK-4 and osteoblast-like
      cells and the interactions between various cytokines in the periprosthetic
      inflammatory environment.

PMID- 22606975
TI  - Novel mutation in potassium channel related gene KCTD7 and progressive myoclonic
      epilepsy.
AB  - Progressive myoclonic epilepsy (PME) is a heterogeneous group of epilepsies
      characterized by myoclonus, seizures and progressive neurological symptoms. The
      index patient was a 6-year old boy showing early-onset therapy resistant PME and
      severe developmental delay. Genome-wide linkage analysis identified several
      candidate regions. The potassium channel tetramerization domain containing 7 gene
      (KCTD7) in the 7q11.21 linkage region emerged as a suitable candidate. Sequence
      analysis revealed a novel homozygous missense mutation (p.R94W) in a highly
      conserved segment of exon 2. This is the second family with PME caused by KCTD7
      mutations, hence KCTD7 mutations might be a recurrent cause of PME.

PMID- 22606976
TI  - Evaluation of the benefit of the user seal check on N95 filtering facepiece
      respirator fit.
AB  - The objective of this study was to better understand the benefit of the user seal
      check step for respirator test subjects in the N95 filtering facepiece respirator
      donning process. To qualify for the study, subjects were required to pass a
      standard quantitative fit test on at least one of the three N95 filtering
      facepiece respirator models: 3M 1860 (cup), 3M 1870 (flat-fold), and Kimberly
      Clark PFR95-270 (duckbill). Eleven subjects were enrolled and performed a series
      of abbreviated, quantitative fit tests where they were randomly asked either to
      perform or not perform a user seal check with 20 different respirator samples of
      each model. The experimental design included 3 respirator models * 10 subjects *
      2 treatment levels with 10 replications. Geometric mean (GM) fit factors and
      percentages of times a fit factor >= 100 was achieved for a donning were compared
      for each subject with and without the user seal check across all models and for
      each model. Higher GM fit factors and smaller geometric standard deviations
      across all models were achieved for 10 of the 11 subjects when performing a user
      seal check compared with not performing a user seal check. Geometric mean fit
      factors of 148, 184, and 156, compared with 126, 187, and 115, respectively, were
      obtained for the 3M 1860, 3M 1870, and Kimberly Clark PFR95-270 models when the
      user seal check was performed vs. not performed. Differences in the GM fit
      factors for the 3M 1860 and Kimberly Clark PFR95-270 models were statistically
      significant (p < 0.05) when performing a user seal check vs. not performing a
      user seal check. These data suggest that there may be some benefit to performing
      the user seal check for at least some models during the filtering facepiece
      respirator donning process for workers who have previously passed a fit test for
      those respirator models. Additional research is needed with larger groups of
      subjects and respirator models/types.

PMID- 22606977
TI  - Peer support and improved quality of life among persons living with HIV on
      antiretroviral treatment: a randomised controlled trial from north-eastern
      Vietnam.
AB  - BACKGROUND: Among people living with HIV (PLHIV) on antiretroviral therapy (ART),
      it is important to determine how quality of life (QOL) may be improved and HIV
      related stigma can be lessened over time. This study assessed the effect of peer
      support on QOL and internal stigma during the first year after initiating ART
      among a cohort of PLHIV in north-eastern Vietnam. METHODS: A sub-sample study of
      a randomised controlled trial was implemented between October 2008 and November
      2010 in Quang Ninh, Vietnam. In the intervention group, participants (n = 119)
      received adherence support from trained peer supporters who visited participants'
      houses biweekly during the first two months, thereafter weekly. In the control
      group, participants (n = 109) were treated according to standard guidelines,
      including adherence counselling, monthly health check and drug refills. Basic
      demographics were measured at baseline. QOL and internal stigma were measured
      using a Vietnamese version of the WHOQOL-HIVBREF and Internal AIDS-related Stigma
      Scale instruments at baseline and 12 months. T-tests were used to detect the
      differences between mean values, multilevel linear regressions to determine
      factors influencing QOL. RESULTS: Overall, QOL improved significantly in the
      intervention group compared to the control group. Among participants initiating
      ART at clinical stages 3 and 4, education at high school level or above and
      having experiences of a family member dying from HIV were also associated with
      higher reported QOL. Among participants at clinical stage 1 and 2, there was no
      significant effect of peer support, whereas having children was associated with
      an increased QOL. Viral hepatitis was associated with a decreased QOL in both
      groups. Lower perceived stigma correlated significantly but weakly with improved
      QOL, however, there was no significant relation to peer support. CONCLUSION: The
      peer support intervention improved QOL after 12 months among ART patients
      presenting at clinical stages 3 and 4 at baseline, but it had no impact on QOL
      among ART patients enrolled at clinical stages 1 and 2. The intervention did not
      have an effect on Internal AIDS-related stigma. To improve QOL for PLHIV on ART,
      measures to support adherence should be contextualized in accordance with
      individual clinical and social needs.

PMID- 22606978
TI  - Primary prophylaxis of overt hepatic encephalopathy in patients with cirrhosis:
      an open labeled randomized controlled trial of lactulose versus no lactulose.
AB  - BACKGROUND AND AIM: Development of overt hepatic encephalopathy (HE) is
      associated with poor prognosis in patients with cirrhosis. Lactulose is used for
      the treatment of HE. There is no study on the prevention of overt HE using
      lactulose in patients who never had HE earlier. METHODS: Consecutive cirrhotic
      patients who never had an episode of overt HE were randomized to receive
      lactulose (Gp-L) or no lactulose (Gp-NL). All patients were assessed by
      psychometry (number connection test [NCT-A and B], figure connection test if
      illiterate [FCT-A and B], digit symbol test [DST], serial dot test [SDT], line
      tracing test [LTT]) and critical flicker frequency test (CFF) at inclusion and
      after 3 months. These patients were followed every month for 12 months for
      development of overt HE. RESULTS: Of 250 patients screened, 120 (48%) meeting the
      inclusion criteria were randomized to Gp-L (n = 60) and Gp-NL (n = 60). Twenty
      (19%) of 105 patients followed for 12 months developed an episode of overt HE.
      Six (11%) of 55 in the lactulose (Gp-L) group and 14 (28%) of 50 in the Gp-NL (P
      = 0.02) developed overt HE. Ten (20%) of 50 patients in Gp-NL and five (9%) of 55
      patients in the Gp-L group died, P = 0.16. Number of patients with minimal
      hepatic encephalopathy (MHE) were comparable in two groups at baseline (Gp-L vs
      Gp-NL, 32:36, P = 0.29). Lactulose improved MHE in 66% of patients in Gp-L.
      Taking a cutoff < 38 Hz sensitivity and specificity of CFF in predicting HE were
      52% and 77% at baseline and 52% and 82% at 3 months of treatment. On multivariate
      analysis, Child's score and presence of MHE at baseline were significantly
      associated with development of overt HE. CONCLUSIONS: Lactulose is effective for
      primary prevention of overt hepatic encephalopathy in patients with cirrhosis.

PMID- 22606979
TI  - Genetic analysis of ancestry, admixture and selection in Bolivian and Totonac
      populations of the New World.
AB  - BACKGROUND: Populations of the Americas were founded by early migrants from Asia,
      and some have experienced recent genetic admixture. To better characterize the
      native and non-native ancestry components in populations from the Americas, we
      analyzed 815,377 autosomal SNPs, mitochondrial hypervariable segments I and II,
      and 36 Y-chromosome STRs from 24 Mesoamerican Totonacs and 23 South American
      Bolivians. RESULTS AND CONCLUSIONS: We analyzed common genomic regions from
      native Bolivian and Totonac populations to identify 324 highly predictive Native
      American ancestry informative markers (AIMs). As few as 40-50 of these AIMs
      perform nearly as well as large panels of random genome-wide SNPs for predicting
      and estimating Native American ancestry and admixture levels. These AIMs have
      greater New World vs. Old World specificity than previous AIMs sets. We identify
      highly-divergent New World SNPs that coincide with high-frequency haplotypes
      found at similar frequencies in all populations examined, including the HGDP
      Pima, Maya, Colombian, Karitiana, and Surui American populations. Some of these
      regions are potential candidates for positive selection. European admixture in
      the Bolivian sample is approximately 12%, though individual estimates range from
      0-48%. We estimate that the admixture occurred ~360-384 years ago. Little
      evidence of European or African admixture was found in Totonac individuals.
      Bolivians with pre-Columbian mtDNA and Y-chromosome haplogroups had 5-30%
      autosomal European ancestry, demonstrating the limitations of Y-chromosome and
      mtDNA haplogroups and the need for autosomal ancestry informative markers for
      assessing ancestry in admixed populations.

PMID- 22606980
TI  - Circulating leukocyte telomere length is highly heritable among families of Arab
      descent.
AB  - BACKGROUND: Telomere length, an indicator of ageing and longevity, has been
      correlated with several biomarkers of cardiometabolic disease in both Arab
      children and adults. It is not known, however, whether or not telomere length is
      a highly conserved inheritable trait in this homogeneous cohort, where age
      related diseases are highly prevalent. As such, the aim of this study was to
      address the inheritability of telomere length in Saudi families and the impact of
      cardiometabolic disease biomarkers on telomere length. METHODS: A total of 119
      randomly selected Saudi families (123 adults and 131 children) were included in
      this cross-sectional study. Anthropometrics were obtained and fasting blood
      samples were taken for routine analyses of fasting glucose and lipid profile.
      Leukocyte telomere length was determined using quantitative real time PCR.
      RESULTS: Telomere length was highly heritable as assessed by a parent-offspring
      regression [h2 = 0.64 (p = 0.0006)]. Telomere length was modestly associated with
      BMI (R(2) 0.07; p-value 0.0087), total cholesterol (R(2) 0.08; p-value 0.0033),
      and LDL-cholesterol (R(2) 0.15; p-value 3 x 10(-5)) after adjustments for gender,
      age and age within generation. CONCLUSION: The high heritability of telomere
      length in Arab families, and the associations of telomere length with various
      cardiometabolic parameters suggest heritable genetic fetal and/or epigenetic
      influences on the early predisposition of Arab children to age-related diseases
      and accelerated ageing.

PMID- 22606981
TI  - Convection-enhanced delivery of M13 bacteriophage to the brain.
AB  - OBJECT: Recent studies indicate that M13 bacteriophage, a very large
      nanoparticle, binds to beta-amyloid and alpha-synuclein proteins, leading to
      plaque disaggregation in models of Alzheimer and Parkinson disease. To determine
      the feasibility, safety, and characteristics of convection-enhanced delivery
      (CED) of M13 bacteriophage to the brain, the authors perfused primate brains with
      bacteriophage. METHODS: Four nonhuman primates underwent CED of M13 bacteriophage
      (900 nm) to thalamic gray matter (4 infusions) and frontal white matter (3
      infusions). Bacteriophage was coinfused with Gd-DTPA (1 mM), and serial MRI
      studies were performed during infusion. Animals were monitored for neurological
      deficits and were killed 3 days after infusion. Tissues were analyzed for
      bacteriophage distribution. RESULTS: Real-time T1-weighted MRI studies of
      coinfused Gd-DTPA during infusion demonstrated a discrete region of perfusion in
      both thalamic gray and frontal white matter. An MRI-volumetric analysis revealed
      that the mean volume of distribution (Vd) to volume of infusion (Vi) ratio of M13
      bacteriophage was 2.3 +/- 0.2 in gray matter and 1.9 +/- 0.3 in white matter. The
      mean values are expressed +/- SD. Immunohistochemical analysis demonstrated mean
      Vd:Vi ratios of 2.9 +/- 0.2 in gray matter and 2.1 +/- 0.3 in white matter. The
      Gd-DTPA accurately tracked M13 bacteriophage distribution (the mean difference
      between imaging and actual bacteriophage Vd was insignificant [p > 0.05], and was
      -2.2% +/- 9.9% in thalamic gray matter and 9.1% +/- 9.5% in frontal white
      matter). Immunohistochemical analysis revealed evidence of additional spread from
      the initial delivery site in white matter (mean Vd:Vi, 16.1 +/- 9.1). All animals
      remained neurologically intact after infusion during the observation period, and
      histological studies revealed no evidence of toxicity. CONCLUSIONS: The CED
      method can be used successfully and safely to distribute M13 bacteriophage in the
      brain. Furthermore, additional white matter spread after infusion cessation
      enhances distribution of this large nanoparticle. Real-time MRI studies of
      coinfused Gd-DTPA (1 mM) can be used for accurate tracking of distribution during
      infusion of M13 bacteriophage.

PMID- 22606982
TI  - Potential proneness of fetal-type posterior cerebral artery to vascular
      insufficiency in parent vessel occlusion of distal posterior cerebral artery
      aneurysms.
AB  - OBJECT: The purpose of this study was to report the potential proneness of a
      fetal-type posterior cerebral artery (PCA) to develop vascular insufficiency in
      parent vessel occlusion of distal PCA aneurysms. METHODS: Between January 2005
      and January 2011, 19 patients (9 females and 10 males) with 20 distal PCA
      aneurysms (16 dissecting and 4 saccular) were treated with endovascular parent
      vessel occlusion. The ages of the patients ranged from 5 to 71 years, with a mean
      age of 40.2 years. Of the 20 aneurysms, 4 were ruptured and 16 were unruptured.
      One of the unruptured aneurysms was additional to another ruptured aneurysm, and
      15 were incidentally discovered. Five aneurysms were smaller than 10 mm, and the
      other 15 were 10 mm or larger. RESULTS: All aneurysms were successfully treated
      with simultaneous coil occlusion of the aneurysm and the parent PCA. One patient
      had hemianopia at the initial presentation, and 2 patients had new persistent
      hemianopia due to insufficient leptomeningeal collateral circulation; in 16
      patients with an intact visual field, no hemianopia developed because there was
      sufficient leptomeningeal collateral circulation. A fetal-type PCA was involved
      in all 3 patients with hemianopia, which was initially presented or caused by
      parent vessel occlusion. However, in the patients without hemianopia, an adult
      type PCA was involved in all cases. CONCLUSIONS: Endovascular treatment via coil
      occlusion of the aneurysm as well as the parent artery can be used to cure distal
      PCA aneurysms. A fetal-type PCA could be an important predictive factor for
      vascular insufficiency in parent vessel occlusion treatment.

PMID- 22606983
TI  - Subdural hematoma.

PMID- 22606985
TI  - Convection-enhanced delivery.

PMID- 22606986
TI  - Theoretical-experimental study of formic acid photofragmentation in the valence
      region.
AB  - Photoionization and photofragmentation studies of formic acid (HCOOH) are
      performed for the valence shell electron ionization process. The total and
      partial ion yield of gaseous HCOOH were collected as a function of photon energy
      in the ultraviolet region, between 11.12 and 19.57 eV. Measurements of the total
      and partial ion yield of gaseous formic acid molecule are performed with a time
      of-flight mass spectrometer at the Synchrotron Light Brazilian Laboratory.
      Density functional theory and time dependent density functional theory are
      employed to calculate the ground and excited electronic state energies of neutral
      and ionic formic acid as well as their fragments and normal vibration modes. The
      ionization potential energies, the stability of electronic excited states of
      HCOOH(+), and the energies of opening fragmentation channels are estimated from
      theoretical-experimental analysis. Additionally, the main formic acid
      photofragmentation pathways by exposition of photons within that energy range are
      determined experimentally. These produced ions primarily have the following
      mass/charge ratios: 46 (HCOOH(+)), 45 (COOH(+)), 29 (HCO(+)), and 18 (H(2)O(+)).

PMID- 22606987
TI  - Induction of immune-related gene expression in Ctenopharyngodon idella kidney
      cells by secondary metabolites from immunostimulatory Alcaligenes faecalis FY-3.
AB  - This study was undertaken to isolate active secondary metabolites from
      immunostimulatory Alcaligenes faecalis FY-3 and evaluate their activities using
      grass carp Ctenopharyngodon idella kidney (CIK) cells. By applying chromatography
      techniques and successive recrystallization, three purified metabolites were
      obtained and identified by spectral data (mass spectrometry and nuclear magnetic
      resonance) as: (1) phenylacetic acid, (2) p-hydroxyphenylacetylamide and (3)
      cyclo-(Gly-(L)-Pro). CIK cells were stimulated by different concentrations (1, 10
      and 100 MUg/ml) of the isolated compounds, and expression of MyD88, IL-1beta, TNF
      alpha, type I-IFN and IL-8 genes at different time points (2, 8 and 24 h) post
      stimulation was quantified by real-time PCR. The known immunostimulatory agent
      lipopolysaccharide (LPS) was used as a positive control. To analyse whether these
      compounds are toxic to the cells, the methyl tetrazolium assay was employed to
      measure changes in cell viability. The obtained results revealed that
      transcribing level of MyD88, an important adaptor molecule in toll-like receptor
      signalling pathway, was augmented remarkably by all the three isolated compounds
      and LPS as early as 2-h exposure. These compounds also induced gene expression of
      cytokines such as IL-1beta, TNF-alpha and type I-IFN. Under the experimental
      conditions, none of the test compounds is toxic to the CIK cells. These findings
      demonstrate that the immunostimulatory properties of the three metabolites
      [phenylacetic acid, p-hydroxyphenylacetylamide and cyclo-(Gly-(L)-Pro)] from A.
      faecalis FY-3 in CIK cells and highlight the potential of using these metabolites
      as immunostimulants in fish aquaculture.

PMID- 22606988
TI  - Click synthesis, aggregation-induced emission, E/Z isomerization, self
      organization, and multiple chromisms of pure stereoisomers of a tetraphenylethene
      cored luminogen.
AB  - It has been difficult to decipher the mechanistic issue whether E/Z isomerization
      is involved in the aggregation-induced emission (AIE) process of a
      tetraphenylethene (TPE) derivative, due to the difficulty in the synthesis of its
      pure E and Z conformers. In this work, pure stereoisomers of a TPE derivative
      named 1,2-bis{4-[1-(6-phenoxyhexyl)-4-(1,2,3-triazol)yl]phenyl}-1,2
      diphenylethene (BPHTATPE) are successfully synthesized. Both isomers show
      remarkable AIE effect (alpha(AIE) >= 322) and high fluorescence quantum yield in
      the solid state (Phi(F) 100%). The conformers readily undergo E/Z isomerization
      upon exposure to a powerful UV light and treatment at a high temperature (>200 
      degrees C). Such conformational change, however, is not observed under normal
      fluorescence spectrum measurement conditions, excluding the involvement of the
      E/Z isomerization in the AIE process of the TPE-based luminogen. The molecules of
      (E)-BPHTATPE self-organize into ordered one-dimensional nanostructures such as
      microfibers and nanorods that show obvious optical waveguide effect. BPHTATPE
      shows rich chromic effects, including mechano-, piezo-, thermo-, vapo-, and
      chronochromisms. Its emission peak is bathochromically shifted by simple grinding
      and pressurization and the spectral change is reversed by fuming with a polar
      solvent, heating at a high temperature, or storing at room temperature for some
      time. The multiple chromic processes are all associated with changes in the modes
      of molecular packing.

PMID- 22606990
TI  - Current practices and evaluation of screening solid organ donors for West Nile
      virus.
AB  - The first cases of West Nile virus (WNV) transmitted through solid organ
      transplantation (SOT) were identified in 2002. Subsequently, 5 additional
      clusters have been reported to public health officials in the United States.
      Based upon a limited number of known cases, patients who acquire WNV from
      infected donor organs might be at higher risk for severe neurologic disease and
      death, compared with patients infected through mosquito bites. In response, some
      organ procurement organizations (OPOs) have instituted pre-transplant screening
      of organ donors for WNV infection. We evaluated the current practices, concerns,
      and challenges related to screening organ donors for WNV in the United States by
      reviewing the relevant medical literature and interviewing key stakeholders.
      Screening organ donors for WNV is not required by national policy. In 2008, 11
      (19%) of 58 OPOs performed WNV screening using nucleic acid amplification testing
      (NAT). These OPOs differ in their screening strategies, NAT performed, and
      logistical challenges. Concerns of delays in receiving NAT results before
      transplant and potential false-positive results leading to organ wasting are
      limitations to more widespread screening. Furthermore, it is unknown if WNV
      screening practices decrease SOT-related morbidity and mortality, or if screening
      is cost-effective. Additional data are needed to assess and improve transplant
      outcomes related to WNV.

PMID- 22606989
TI  - Dual role of autophagy in HIV-1 replication and pathogenesis.
AB  - Autophagy, the major mechanism for degrading long-lived intracellular proteins
      and organelles, is essential for eukaryotic cell homeostasis. Autophagy also
      defends the cell against invasion by microorganisms and has important roles in
      innate and adaptive immunity. Increasingly evident is that HIV-1 replication is
      dependent on select components of autophagy. Fittingly, HIV-1 proteins are able
      to modulate autophagy to maximize virus production. At the same time, HIV-1
      proteins appear to disrupt autophagy in uninfected cells, thereby contributing to
      CD4+ cell death and HIV-1 pathogenesis. These observations allow for new
      approaches for the treatment and possibly the prevention of HIV-1 infection. This
      review focuses on the relationship between autophagy and HIV-1 infection.
      Discussed is how autophagy plays dual roles in HIV-1 replication and HIV-1
      disease progression.

PMID- 22606991
TI  - Pharmacokinetics of a continuous rate infusion of ceftiofur sodium in normal
      foals.

PMID- 22606992
TI  - The weekend matters: exploring when and how nurses best recover from work stress.
AB  - AIM: This article is a report of a comparative study examining nurses' levels of
      emotional exhaustion and vigour after a short respite taken on weekends as
      compared with two midweek days taken off. BACKGROUND: Recovery from work stress -
      a respite experience that generates replenishing of psychological and physical
      resources that have been depleted by meeting effortful demands - is crucial to
      offset future deleterious consequences to mental and physical health. DESIGN:
      Longitudinal panel survey. METHOD: Nurses (n = 400) completed questionnaires
      during 2010-2011 on three occasions: (1) Before the respite (weekend or midweek),
      we measured the timing of the respite and emotional exhaustion and vigour; (2)
      during the respite we measured respite experiences; and (3) after the respite we
      re-measured emotional exhaustion and vigour. RESULTS: Nurses' emotional
      exhaustion was significantly lower and their vigour significantly higher after a
      short weekend respite than after two-midweek-days taken off. Specific experiences
      during the respite can compensate for the inferior recovery process on weekdays
      compared with weekends: emotional exhaustion levels of nurses who experienced
      high relaxation during their respite did not differ whether the respite was at
      the midweek or weekend. Vigour levels of nurses who experienced control during
      their respite did not differ whether their respite was midweek or at the weekend.
      CONCLUSIONS: Insights gained on leisure experiences carry important practical
      implications for nurses and nursing managers. Staff nurses and their managers
      should be educated in how to recover from work during leisure time, including
      preferring weekend on midweek respites and engagement in relaxation and control
      experiences as much as possible.

PMID- 22606993
TI  - Improved characterization of gas-particle partitioning for per- and
      polyfluoroalkyl substances in the atmosphere using annular diffusion denuder
      samplers.
AB  - Gas-phase perfluoroalkyl carboxylic acids (PFCAs) sorb strongly on filter
      material (i.e., GFF, QFF) used in conventional high volume air samplers, which
      results in an overestimation of the particle-phase concentration. In this study,
      we investigated an improved technique for measuring the gas-particle partitioning
      of per- and polyfluoroalkyl substances (PFASs) using an annular diffusion denuder
      sampler. Samples were analyzed for 7 PFAS classes [i.e., PFCAs, perfluoroalkane
      sulfonic acids (PFSAs), fluorotelomer alcohols (FTOHs), fluorotelomer
      methacrylates (FTMACs), fluorotelomer acrylates (FTACs), perfluorooctane
      sulfonamides (FOSAs), and perfluorooctane sulfonamidoethanols (FOSEs)]. The
      measured particulate associated fraction (Phi') using the diffusion denuder
      sampler generally followed the trend FTACs (0%) < FTOHs (~8%) < FOSAs (~21%) <
      PFSAs (~29%) < FOSEs (~66%), whereas the Phi' of the C(8)-C(18) PFCAs increased
      with carbon chain length, and ranged from 6% to 100%. The ionizability of some
      PFASs, when associated with particles, is an important consideration when
      calculating the gas-particle partitioning coefficient as both ionic and neutral
      forms can be present in the particles. Here we differentiate between a gas
      particle partitioning coefficient for neutral species, K(p), and one that
      accounts for both ionic and neutral species of a compound, K(p)'. The measured
      K(p)' for PFSAs and PFCAs was 4-5 log units higher compared to the interpolated
      K(p) for the neutral form only. The measured K(p)' can be corrected (to apply to
      the neutral form only) with knowledge of the pK(a) of the chemical and the pH of
      the condensed medium ("wet" particle or aqueous aerosol). The denuder-based
      sampling of PFASs has yielded a robust data set that demonstrates the importance
      of atmospheric pH and chemical pK(a) values in determining gas-particle
      partitioning of PFASs.

PMID- 22606994
TI  - Temporal sequence in the formation of midline dermis and dorsal vertebral
      elements in avian embryos.
AB  - Somites compartmentalize into a dorsal epithelial dermomyotome and a ventral
      mesenchymal sclerotome. While sclerotomes give rise to vertebrae and
      intervertebral discs, dermomyotomes contribute to skeletal muscle and epaxial
      dermis. Bone morphogenetic protein (BMP)-signals from the lateral mesoderm induce
      the lateral portion of the dermomyotome to form chondrogenic precursor cells,
      forming the cartilage of the scapula blade. The fact that BMPs are expressed in
      the roof plate of the neural tube where they induce cartilage formation led to
      the question why cells migrating from the medial part of the dermomyotome do not
      undergo chondrogenic differentiation and do not contribute to the dorsal part of
      the vertebrae. In the present study, we traced dermomyotomal derivatives by using
      the quail-chick marker technique. Our study reveals a temporal sequence in the
      formation of the vertebral cartilage and the midline dermis. The dorsal
      mesenchyme overlying the roof plate of the neural tube is formed prior to the de
      epithelialization of the dermomyotome. Dermomyotomal cells start to migrate
      medially into the sub-ectodermal space to form the midline dermis after
      chondrogenesis of the dorsal mesenchyme has occurred. This time delay between
      chondrogenesis of the dorsal vertebra and dermal formation allows an undisturbed
      development of these two tissue components within a narrow region of the embryo.

PMID- 22606995
TI  - The four principles: can they be measured and do they predict ethical decision
      making?
AB  - BACKGROUND: The four principles of Beauchamp and Childress--autonomy, non
      maleficence, beneficence and justice--have been extremely influential in the
      field of medical ethics, and are fundamental for understanding the current
      approach to ethical assessment in health care. This study tests whether these
      principles can be quantitatively measured on an individual level, and then
      subsequently if they are used in the decision making process when individuals are
      faced with ethical dilemmas. METHODS: The Analytic Hierarchy Process was used as
      a tool for the measurement of the principles. Four scenarios, which involved
      conflicts between the medical ethical principles, were presented to participants
      who then made judgments about the ethicality of the action in the scenario, and
      their intentions to act in the same manner if they were in the situation.
      RESULTS: Individual preferences for these medical ethical principles can be
      measured using the Analytic Hierarchy Process. This technique provides a useful
      tool in which to highlight individual medical ethical values. On average,
      individuals have a significant preference for non-maleficence over the other
      principles, however, and perhaps counter-intuitively, this preference does not
      seem to relate to applied ethical judgements in specific ethical dilemmas.
      CONCLUSIONS: People state they value these medical ethical principles but they do
      not actually seem to use them directly in the decision making process. The
      reasons for this are explained through the lack of a behavioural model to account
      for the relevant situational factors not captured by the principles. The
      limitations of the principles in predicting ethical decision making are
      discussed.

PMID- 22606996
TI  - Influenza viral infections among the Iranian Hajj pilgrims returning to Shiraz,
      Fars province, Iran.
AB  - BACKGROUND: Annually over two million Muslims from across the world converge on
      Mecca to perform the Hajj pilgrimage. Overcrowding at the Hajj facilitates spread
      of communicable diseases, especially respiratory infections. The aim of this
      study was to determine the attack rate of seasonal and pandemic influenza among
      returning Iranian pilgrims after the 2009 Hajj. METHODS: Clinical data and throat
      swabs were collected at Shiraz airport from symptomatic Iranian pilgrims of Fars
      province who were returning from the Hajj between 15 and 21 December 2009. The
      specimens were tested at the Shiraz University of Medical Sciences Influenza
      Research Center for influenza viruses by cell culture and real-time reverse
      transcriptase polymerase chain reaction (RTrtPCR) according to standard protocol.
      FINDINGS: Out of 3000 pilgrims from Fars province who attended the Hajj 2009, 275
      symptomatic pilgrims were recruited into this study. Pilgrims had fever, cough,
      muscle ache and sore throat in various combinations. Twenty-five (9.1%) pilgrims
      had influenza by virus culture and these were as follows: influenza B (n=17),
      influenza A H3N2 (n=8) and pandemic H1N1 (n=5), whereas 33 (12%) had influenza by
      RTrtPCR: influenza B (n=20), influenza A H3N2 (n=8) and pandemic H1N1 (n=5).
      INTERPRETATION: Both seasonal and pandemic influenza infections occurred among
      the Iranian Hajj pilgrims; seasonal viruses were more common than the pandemic
      viruses even though all pilgrims were vaccinated against seasonal influenza.

PMID- 22606997
TI  - Development and plasticity of thalamocortical systems.

PMID- 22606998
TI  - Unveiling the diversity of thalamocortical neuron subtypes.
AB  - Our current understanding of thalamocortical (TC) circuits is largely based on
      studies investigating so-called 'specific' thalamic nuclei, which receive and
      transmit sensory-triggered input to specific cortical target areas. TC neurons in
      these nuclei have a striking point-to-point topography and a stereotyped laminar
      pattern of termination in the cortex, which has made them ideal models to study
      the organization, plasticity, and development of TC circuits. However, despite
      their experimental importance, neurons within these nuclei only represent a
      fraction of all thalamic neurons and do not reflect the diversity of the TC
      neuron population. Here we review the distinct subtypes of projection neurons
      that populate the thalamus, both within and across anatomically-defined nuclei,
      with regard to differences in their morphology, input/output connectivity and
      target specificity, as well as more recent findings on their neuron type-specific
      gene expression and development. We argue that a detailed understanding of the
      biology of TC neurons is critical to understand the role of the thalamus in
      normal and pathological perception, voluntary movement, cognition and attention.

PMID- 22606999
TI  - Patterning of pre-thalamic somatosensory pathways.
AB  - The topographical mapping of input is a fundamental organizing principle of
      sensory pathways. In the somatosensory system, a precise topographical
      representation of the face is first generated in the brainstem and then
      faithfully replicated in the thalamus and cortex. Although our knowledge of the
      distinct polysynaptic pathways that link cutaneous mechanoreceptors of the face
      with neocortical neurons has recently expanded, the molecular mechanisms
      controlling their neuron-type-specific assembly during development remain poorly
      understood. The increasing availability of genetic tools that enable manipulation
      of these developing circuits with cellular resolution now opens new perspectives
      in our understanding of the molecular mechanisms through which input from the
      periphery is converted into patterned central pathways.

PMID- 22607001
TI  - Diversity of thalamic progenitor cells and postmitotic neurons.
AB  - The vertebrate thalamus contains multiple sensory nuclei, and relays sensory
      information to corresponding cortical areas. Moreover, the thalamus actively
      regulates information transmission to the cortex by modulating the response
      magnitude, firing mode and synchrony of neurons according to behavioral demands.
      The thalamus serves many other functions including motor control, learning and
      memory, and emotion. Such functional importance of the thalamus necessitates a
      better understanding of its developmental mechanisms. In this review, we will
      first describe the morphological organization of the developing thalamus. We will
      then discuss how neuronal diversity is generated and nuclei are formed during
      thalamic development. The first step in generating neuronal diversity is the
      formation of spatial diversity of thalamic progenitor cells, which is controlled
      by locally-expressed signaling molecules such as Sonic hedgehog (Shh), Wnt
      proteins and Fgf8. Lastly we will describe the roles of several transcription
      factors in specification of neuronal identity and nuclei formation in the
      thalamus. Our review will provide a molecular perspective for the organization of
      the thalamus prior to thalamus-cortex circuit formation.

PMID- 22607000
TI  - Development and critical period plasticity of the barrel cortex.
AB  - In primary sensory neocortical areas of mammals, the distribution of sensory
      receptors is mapped with topographic precision and amplification in proportion to
      the peripheral receptor density. The visual, somatosensory and auditory cortical
      maps are established during a critical period in development. Throughout this
      window in time, the developing cortical maps are vulnerable to deleterious
      effects of sense organ damage or sensory deprivation. The rodent barrel cortex
      offers an invaluable model system with which to investigate the mechanisms
      underlying the formation of topographic maps and their plasticity during
      development. Five rows of mystacial vibrissa (whisker) follicles on the snout and
      an array of sinus hairs are represented by layer IV neural modules ('barrels')
      and thalamocortical axon terminals in the primary somatosensory cortex. Perinatal
      damage to the whiskers or the sensory nerve innervating them irreversibly alters
      the structural organization of the barrels. Earlier studies emphasized the role
      of the sensory periphery in dictating whisker-specific brain maps and patterns.
      Recent advances in molecular genetics and analyses of genetically altered mice
      allow new insights into neural pattern formation in the neocortex and the
      mechanisms underlying critical period plasticity. Here, we review the development
      and patterning of the barrel cortex and the critical period plasticity.

PMID- 22607002
TI  - Insights into the complex influence of 5-HT signaling on thalamocortical axonal
      system development.
AB  - The topographic organization of the thalamocortical axons (TCAs) in the barrel
      field (BF) in the rodent primary somatosensory cortex results from a succession
      of temporally and spatially precise developmental events. Prenatally, growth and
      guidance mechanisms enable TCAs to navigate through the forebrain and reach the
      cortex. Postnatally, TCAs grow into the cortex, and the refinement of their
      terminal arborization pattern in layer IV creates barrel-like structures. The
      combined results of studies performed over the past 20 years clearly show that
      serotonin (5-hydroxytryptamine; 5-HT) signaling modulates these pre- and early
      postnatal developmental processes. In this context, 5-HT signaling can purposely
      be described as 'modulating' rather than 'controlling' because developmental
      alterations of 5-HT synthesis, uptake or degradation either have a dramatic,
      moderate or no effect at all on TCA pathway and BF formation. In this review we
      summarize and compare the outcomes of diverse pharmacological and genetic
      manipulations of 5-HT signaling on TCA pathway and BF formation, in an attempt to
      understand these discrepancies.

PMID- 22607005
TI  - Shaping brain connections through spontaneous neural activity.
AB  - An overwhelming number of observations demonstrate that neural activity and
      genetic programs interact to specify the composition and organization of neural
      circuits during all stages of development. Spontaneous neuronal activities have
      been documented in several developing neural regions in both invertebrates and
      vertebrates, and their roles are mostly conserved among species. Among these
      roles, Ca(2+)  spikes and levels of electrical activity have been shown to
      regulate neurite growth, axon extension and axon branching. Here, we review
      selected findings concerning the role of spontaneous activity on circuit
      development.

PMID- 22607004
TI  - Termination and initial branch formation of SNAP-25-deficient thalamocortical
      fibres in heterochronic organotypic co-cultures.
AB  - We are interested in the role of neural activity mediated through regulated
      vesicular release in the stopping and early branching of the thalamic projections
      in the cortex. Axon outgrowth, arrival at the cortical subplate, side-branch
      formation during the waiting period and cortical plate innervation of embryonic
      thalamocortical projections occurs without major abnormalities in the absence of
      regulated release in Snap25 (-/-) null mutant mice [Washbourne et al. (2002) Nat.
      Neurosci. 5:19-26; Molnar et al. (2002) J. Neurosci. 22:10313-10323]. The fact
      that Snap25 (-/-) null mutant mice die at birth limited our previous experiments
      to the prenatal period. We therefore investigated the behaviour of thalamic
      projections in co-culture paradigms by using heterochronic thalamic [embryonic
      day (E)16-E18] and cortical [postnatal day (P)0-P3] explants, in which the
      stopping and branching behaviour has been previously documented. Our current co
      culture experiments established that thalamic projections from E16-E18
      Snap25(+/+) or Snap25 (-/-) explants behaved in an identical fashion in P0-P3
      Snap25 (+/+) cortical explants after 7 days in vitro. Thalamic projections from
      Snap25 (-/-) explants developed similar patterns of fibre ingrowth to the cortex,
      and stopped and formed branches at a similar depth in the Snap25(+/+) cortical
      slice as in control cultures. These results imply that thalamic projections can
      reach their ultimate target cells in layer 4, stop, and start to develop branches
      in the absence of regulated vesicular transmitter release from their own
      terminals.

PMID- 22607003
TI  - Mechanisms controlling the guidance of thalamocortical axons through the
      embryonic forebrain.
AB  - Thalamocortical axons must cross a complex cellular terrain through the
      developing forebrain, and this terrain has to be understood for us to learn how
      thalamocortical axons reach their destinations. Selective fasciculation,
      guidepost cells and various diencephalic and telencephalic gradients have been
      implicated in thalamocortical guidance. As our understanding of the relevant
      forebrain patterns has increased, so has our knowledge of the guidance
      mechanisms. Our aim here is to review recent observations of cellular and
      molecular mechanisms related to: the growth of thalamofugal projections to the
      ventral telencephalon, thalamic axon avoidance of the hypothalamus and extension
      into the telencephalon to form the internal capsule, the crossing of the pallial
      subpallial boundary, and the growth towards the cerebral cortex. We shall review
      current theories for the explanation of the maintenance and alteration of
      topographic order in the thalamocortical projections to the cortex. It is now
      increasingly clear that several mechanisms are involved at different stages of
      thalamocortical development, and each contributes substantially to the eventual
      outcome. Revealing the molecular and cellular mechanisms can help to link
      specific genes to details of actual developmental mechanisms.

PMID- 22607006
TI  - Thioredoxin reductase inhibition elicits Nrf2-mediated responses in Clara cells:
      implications for oxidant-induced lung injury.
AB  - AIMS: Pulmonary oxygen toxicity contributes to lung injury in newborn and adult
      humans. We previously reported that thioredoxin reductase (TrxR1) inhibition with
      aurothioglucose (ATG) attenuates hyperoxic lung injury in adult mice. The present
      studies tested the hypothesis that TrxR1 inhibition protects against the effects
      of hyperoxia via nuclear factor E2-related factor 2 (Nrf2)-dependent mechanisms.
      RESULTS: Both pharmacologic and siRNA-mediated TrxR1 inhibition induced robust
      Nrf2 responses in murine-transformed Clara cells (mtCC). While TrxR1 inhibition
      did not alter the susceptibility of cells to the effects of hyperoxia,
      glutathione (GSH) depletion after TrxR1 inhibition markedly enhanced the
      hyperoxic susceptibility of cultured mtCCs. Finally, in vivo data revealed dose
      dependent increases in the expression of the Nrf2 target gene NADPH:quinone
      oxidoreductase 1 (NQO1) in the lungs of ATG-treated adult mice. INNOVATION: TrxR1
      inhibition activates Nrf2-dependent antioxidant responses in mtCCs in vitro and
      in adult murine lungs in vivo, providing a plausible mechanism for the protective
      effects of TrxR1 inhibition in vivo. CONCLUSION: GSH-dependent enzyme systems in
      mtCCs may be of greater importance for protection against hyperoxic exposure than
      are TrxR-dependent systems. The induction of Nrf2 activation via TrxR1 inhibition
      represents a novel therapeutic strategy that attenuates oxidant-mediated lung
      injury. Similar expression levels of TrxR1 in newborn and adult mouse or human
      lungs broaden the potential clinical applicability of the present findings to
      both neonatal and adult oxidant lung injury.

PMID- 22607008
TI  - Limits and perspective of oral therapy with statins and aspirin for the
      prevention of symptomatic cholesterol gallstone disease.
AB  - The prevalence of gallstones disease in Western countries is 10 - 15%. Gallstones
      can be one of two types - cholesterol or pigment - with cholesterol gallstones
      representing nearly the 80% of the total. Cholesterol and pigment gallstones have
      different predisposing factors: cholesterol gallstones are related to
      supersaturated bile in cholesterol, whereas black pigment gallstones are related
      to hyperbilirubinbilia factors (hemolysis, etc.); these are necessary, but not
      sufficient, factors to produce gallstones in vivo. Gall bladder mucosa factors
      (gall bladder secretion of mucin, local bile stasis and production of endogenous
      biliary beta-glucuronidase) may coexist with the aforementioned factors and
      facilitate gallstone nucleation and growth. The gold-standard treatment for
      symptomatic gallstones is laparoscopic cholecystectomy. Several studies have
      reported a significant reduction in the onset of symptomatic gallstones disease
      in patients undergoing chronic therapy with statins, which can reduce bile
      cholesterol saturation. Aspirin, which has been shown to reduce the local
      production of gall bladder mucins (mucosal or parietal factors of gallstone
      formation) in animal experimental models, does not appear to reduce the risk of
      symptomatic gallstones disease when tested alone. The new horizon of oral therapy
      for the prevention of symptomatic gallstone disease needs to evaluate the long
      term effect of statins and chronic aspirin administration in patients with
      dyslipidemia and/or atherosclerosis.

PMID- 22607009
TI  - Sunitinib  malate for the treatment of renal cell carcinoma.
AB  - INTRODUCTION: Over the past decade, a greater understanding into the molecular
      pathogenesis of renal cell carcinoma (RCC) has led to major advances in treatment
      options. Sunitinib is an oral, small-molecule, multi-targeted receptor tyrosine
      kinase inhibitor (TKI) that targets a number of receptors, including vascular
      endothelial growth factor receptors (VEGFR) and platelet-derived growth factor
      receptors (PDGFR). Sunitinib was one of the first targeted agents studied in
      metastatic RCC (mRCC) and is currently used worldwide in the management of mRCC.
      AREAS COVERED: This drug evaluation addresses the preclinical and clinical
      development of sunitinib. It provides an in-depth discussion of the Phase II data
      that led to its approval in mRCC and the subsequent Phase III clinical trial
      comparing sunitinib to interferon-alpha. More recent data from the large
      international expanded access trial, in non-clear cell carcinoma patients,
      different dosing schedule studies and safety issues are also discussed. Finally,
      areas for the future use of sunitinib, including in the adjuvant setting, are
      reviewed. EXPERT OPINION: Since the FDA approved sunitinib for advanced RCC in
      January 2006, much more has been learned about its efficacy and tolerability.
      Over the past decade of its clinical use, it has become clear that expertise is
      required when prescribing sunitinib, in terms of maximizing dose, anticipating
      and managing side effects, and assessing responses. In the future, a better
      understanding of sunitinib's role compared with other VEGF TKIs and mTOR
      inhibitors, and in other roles such as the adjuvant setting or in non-clear cell
      pathology, will become evident.

PMID- 22607010
TI  - Oxybutynin  gel for the treatment of overactive bladder.
AB  - INTRODUCTION: Overactive bladder (OAB) is a common condition that has a profound
      impact on an individual's overall health and quality of life. Muscarinic receptor
      antagonists are the mainstay of oral pharmacotherapy for OAB. While all of the
      medications in this class are significantly more effective than placebo, they are
      also associated with more adverse events that may limit their overall use.
      Transdermal application of oxybutynin has been shown to avoid first-pass
      metabolism and, thus, may be associated with fewer antimuscarinic side effects.
      AREAS COVERED: This paper reviews the pharmacology of transdermal oxybutynin gel
      and summarizes the available data regarding this product in the treatment of OAB.
      It also discusses the role of this product in the OAB treatment armamentarium.
      EXPERT OPINION: Oxybutynin transdermal gel has been shown to have significant
      advantages over placebo, in terms of urgency incontinence episodes, urinary
      frequency and voided volume in a Phase III study. Application site effects were
      higher in the gel group, but the incidence of antimuscarinic side effects were
      lower than those seen with oral preparations. The lower incidence of skin side
      effects, as compared with the transdermal patch, may confer a theoretical
      advantage toward the gel product. While promising, unanswered questions remain
      regarding persistence with treatment after this mode of therapy, and head-to-head
      comparisons with other antimuscarinics are absent.

PMID- 22607011
TI  - Extended-release niacin with laropiprant : a review on efficacy, clinical
      effectiveness and safety.
AB  - INTRODUCTION: Although treatment with statins reduces cardiovascular (CV) events
      in patients with dyslipidemia, a residual 60 - 70% CV risk remains. This CV risk
      may be inversely related to high-density lipoprotein-cholesterol (HDL-C).
      Interest in niacin has re-emerged because of its HDL-C raising effects. The
      flushing associated with niacin which has previously affected patient compliance
      can now be significantly blocked with laropiprant (LRPT). AREAS COVERED: This
      review aims to assess the efficacy, clinical effectiveness and safety of extended
      release niacin (ERN) with LRPT. The authors searched PubMed and MEDLINE for
      literature published between January 2006 and November 2011, for efficacy,
      clinical effectiveness and safety reports of ERN with LRPT. EXPERT OPINION:
      Niacin has been shown to prevent CV events, reduce mortality and has beneficial
      effects on vascular endothelial function. Evidence suggests that this is due to
      its broad-spectrum lipid altering properties, including lowering lipoprotein (a)
      (Lp(a)), and its pleiotropic actions. While side effects associated with niacin
      have limited its use in the past, the extended-release formulations and co
      administration of LRPT have increased its tolerability, particularly by reducing
      flushing. The authors advise that ERN should be used in patients with a high risk
      of cardiovascular disease, who have failed to reach conventional targets.

PMID- 22607013
TI  - Ultrastructural basis of the failure of oral dissolution therapy with bile salts
      and/or statin for cholesterol gallstones.

PMID- 22607014
TI  - Facile preparation of zwitterion-stabilized superparamagnetic iron oxide
      nanoparticles (ZSPIONs) as an MR contrast agent for in vivo applications.
AB  - We describe a simple method for synthesizing superparamagnetic nanoparticles
      (SPIONs) as small, stable contrast agents for magnetic resonance imaging (MRI)
      based on sulfobetaine zwitterionic ligands. SPIONs synthesized by thermal
      decomposition were coated with zwitterions to impart water dispersibility and
      high in vivo stability through the nanoemulsion method. Zwitterion surfactant
      coating layers are formed easily on oleic acid-stabilized SPIONs via hydrophobic
      and van der Waals interactions. Our zwitterion-coated SPIONs (ZSPIONs) had
      ultrathin (~5 nm) coating layers with mean sizes of 12.0 +/- 2.5 nm, as measured
      by dynamic light scattering (DLS). Upon incubation in 1 M NaCl and 10% FBS, the
      ZSPIONs showed high colloidal stabilities without precipitating, as monitored by
      DLS. The T2 relaxivity coefficient of the ZSPIONs, obtained by measuring the
      relaxation rate on the basis of the iron concentration, was 261 mM(-1) s(-1).
      This value was much higher than that of the commercial T2 contrast agent because
      of the ultrathin coating layer. Furthermore, we confirmed that ZSPIONs can be
      used as MR contrast agents for in vivo applications such as tumor imaging and
      lymph node mapping.

PMID- 22607015
TI  - Lewis acids as alpha-directing additives in glycosylations by using 2,3-O
      carbonate-protected glucose and galactose thioglycoside donors based on
      preactivation protocol.
AB  - Catalytic or stoichiometric amounts of Lewis acids were found to be very
      effective alpha-directing additives in the stereoselective glycosylations of
      diverse 2,3-O-carbonate-protected glucose and galactose thioglycoside donors by
      preactivation protocol. The poor stereoselectivities of 4,6-di-O-acetyl-2,3-O
      carbonate protected thioglycoside donors in glycosyl coupling reactions were
      greatly improved, and excellent alpha-stereoselectivities were achieved by the
      addition of 0.2 equiv of BF(3).OEt(2). On the other hand, the beta-selectivities
      of 4,6-di-O-benzyl-2,3-O-carbonate-protected thioglucoside donor toward
      glycosylations were reversed completely to the alpha-selectivities by the use of
      1 equiv of SnCl(4), making the stereoselectivity controllable. Furthermore, the
      poor stereoselectivities of 4,6-di-O-benzyl-2,3-O-carbonate-protected
      thiogalactoside donor in glycosylations were also improved by using SnCl(4) as
      additive.

PMID- 22607016
TI  - Increasing mastectomy rates among all age groups for early stage breast cancer: a
      10-year study of surgical choice.
AB  - First-line surgical options for early stage breast cancer and ductal carcinoma in
      situ include breast conserving surgery or mastectomy. We analyzed factors that
      influence the receipt of mastectomy and resultant trends over time. Registry
      analysis was carried out for 21,869 women who underwent up-front surgical
      treatment for stage 0, I or II breast cancer between 1998 and 2007 using data
      from the Kentucky Cancer Registry. We examined the trend of treatment over time
      and assessed the probability of receiving mastectomy using multivariate logistic
      regression. Overall, 54.5% of women received breast conservation and 45.5%
      received mastectomy over a 10-year period (annual BCS rate range: 46.9-61.2%).
      The overall mastectomy rate substantially decreased from 53.1% in 1998 to 38.8%
      in 2005 (p < 0.0001), but then increased to 45% in 2007 (p < 0.001). Between 2005
      and 2007, the increase in mastectomies in the age groups of <50 years, 50-69
      years, and >= 70 years was 7.5% (p = 0.0351), 4.9% (p = 0.0132) and, 8.0% (p =
      0.0283), respectively. On multivariate analysis, the rate of receiving mastectomy
      was drastically higher for women with stage I or II (versus in situ) disease and
      moderate or poorly differentiated (versus well differentiated) histology. The
      rate was modestly higher for uninsured and government-insured (versus privately
      insured) patients, patients older than 70 years (versus younger), rural (versus
      urban) location, receptor negative (versus receptor positive) disease, and
      unusual histologies (versus ductal and lobular histology). There was no
      statistically significant difference in surgical choice with regard to race.
      Determinants of mastectomy for in situ and early stage breast cancer include
      stage, histology, age, insurance status, county of residence, receptor status.
      The rate of mastectomy declined until 2005 and is now increasing across all age
      groups, especially for women < 50 years and >= 70 years.

PMID- 22607017
TI  - Bayes factor based on the trend test incorporating Hardy-Weinberg disequilibrium:
      more power to detect genetic association.
AB  - In the analysis of case-control genetic association, the trend test and Pearson's
      test are the two most commonly used tests. In genome-wide association studies
      (GWAS), Bayes factor (BF) is a useful tool to support significant P-values, and a
      better measure than P-value when results are compared across studies with
      different sample sizes. When reporting the P-value of the trend test, we propose
      a BF directly based on the trend test. To improve the power to detect association
      under recessive or dominant genetic models, we propose a BF based on the trend
      test and incorporating Hardy-Weinberg disequilibrium in cases. When the true
      model is unknown, or both the trend test and Pearson's test or other robust tests
      are applied in genome-wide scans, we propose a joint BF, combining the previous
      two BFs. All three BFs studied in this paper have closed forms and are easy to
      compute without integrations, so they can be reported along with P-values,
      especially in GWAS. We discuss how to use each of them and how to specify priors.
      Simulation studies and applications to three GWAS are provided to illustrate
      their usefulness to detect nonadditive gene susceptibility in practice.

PMID- 22607019
TI  - Liquid cocaine body packers.
AB  - INTRODUCTION: Internal transport of cocaine in liquid form by body packers has
      been reported by the media, but there are no scientific publications on the
      clinical aspects of this practice. CASE REPORTS: We describe two cases of body
      packers bearing 36 and 4 packs containing liquid cocaine in the colon and rectum,
      respectively. Abdominal X-ray in both cases showed radiological characteristics
      that differed from those commonly found in body packers transporting solid-state
      cocaine, heroin, or cannabis (packs with lower radiological density, diffuse
      borders, elongated and resembling feces). Both patients were asymptomatic and
      were discharged from the emergency department 6 hours after admission.
      DISCUSSION: Expulsion time after laxative administration was shorter compared to
      "solid" drug body packers. The diagnostic sensitivity of different imaging
      techniques remains to be established for internally concealed liquid drugs. There
      have been press reports of internal pack rupture resulting in death, so caution
      is required. The lower radiographic density of liquid cocaine condom packs and
      their adaptability to intestinal anatomy make them difficult to detect using
      plain abdominal radiography. Physicians should be aware of the possibility of
      false negative radiological findings in these cases.

PMID- 22607018
TI  - Urine colour after radical prostatectomy predicts urinary leakage at the
      vesicourethral anastomosis.
AB  - OBJECTIVE: The aim of this investigation was to determine whether postoperative
      urine colour could be used as a predictor for the presence or absence of a
      urinary leakage at the vesicourethral anastomosis after open radical
      prostatectomy. MATERIAL AND METHODS: In this prospective study, the urine colour
      of 223 patients who underwent open radical prostatectomy due to histologically
      proven localized prostate cancer was assessed macroscopically and microscopically
      on postoperative day (POD) 6, 7 and 8. All patients underwent evaluation of
      perianastomotic extravasation by retrograde cystography on POD 8. Baseline
      characteristics included age; prostate-specific antigen; prostate volume; tumour,
      node, metastasis classification; and Gleason score. RESULTS: The urine colour was
      a highly significant predictor for perianastomotic extravasation in cystography
      when it was red on POD 6, 7 and 8. The sensitivity and specificity of urine
      colour as a predictor for extravasation were 71.4% and 83.2% on POD 6, 71.4% and
      85.8% on POD 7, and 81.8% and 90.9% on POD 8, respectively, with a clear or
      slightly ensanguined urine colour. The negative and positive predictive values
      were 98.6% and 81.8%, respectively. CONCLUSION: A cystography can be omitted if
      the patient demonstrates a clear urine colour on POD 8, without an increased risk
      of missing a perianastomotic extravasation.

PMID- 22607020
TI  - The effects of proteinuria on urinary cystatin-C and glomerular filtration rate
      calculated by serum cystatin-C.
AB  - BACKGROUND: The measurement of glomerular filtration rate (GFR) applying serum
      creatinine (Cr) does not reflect the GFR of patients accurately, and thus
      recently, studies on the measurement of GFR applying serum cystatin-C (Cys-C)
      have been conducted. We investigated the relationship between Cys-C and
      proteinuria in patients with chronic kidney disease. METHODS: We compared the
      biochemical test, including serum Cys-C, the amount of proteinuria and the
      concentration of Cys-C measured by the 24-h urine test, and the difference of GFR
      on 105 patients who visited our hospital in 6 months (January to June 2007).
      RESULTS: Among 105 patients, 58 patients were males, and the mean age was 56.74
      +/- 16.31 years. With regard to underlying diseases, the group with diabetes had
      76 patients and the group showing nephrotic proteinuria [nephrotic syndrome (NS)]
      had 29 patients. The GFR-Cys-C in the NS group (44.17 +/- 26.32 mL/min) was
      higher than in the non-NS group (33.68 +/- 14.29 mL/min; p = 0.041). The
      fractional excretion (FE) of Cys-C increased according to FE of albumin ( p =
      0.000) and GFR-modification of diet in renal disease (MDRD) equation (p = 0.000).
      Serum Cys-C increased according to corrected urine Cys-C (p = 0.010). The GFR
      calculated by serum Cys-C decreased according to FE of albumin (p = 0.003). The
      degree of difference between GFR-Cys-C and GFR-MDRD was negatively correlated
      according to the FE of albumin (p = 0.001). CONCLUSION: We confirmed that urinary
      excretion of Cys-C could be altered by previously known mechanisms such as
      proteinuria. Difference between GFR-Cys-C and GFR-MDRD was negatively correlated
      according to FE of albumin.

PMID- 22607021
TI  - Changing perspective of reasons for not performing laser-assisted in situ
      keratomileusis among candidates in a university eye clinic.
AB  - BACKGROUND: The aim was to retrospectively analyse the reasons for not performing
      laser-assisted in situ keratomileusis (LASIK) surgery among refractive surgery
      candidates at a university eye clinic. METHODS: Case records of patients who
      presented to a university eye clinic between June 2005 and June 2010 for
      consideration for LASIK surgery were examined. Cases that did not undergo LASIK
      were selected for analysis. Reasons for not performing surgery in these cases
      were analysed. RESULTS: In total, 552 patients requested LASIK between July 2005
      and June 2010 and 377 (68.3 per cent) of them received refractive surgery. Among
      175 (31.7 per cent) patients who did not get LASIK, 62 (35.4 per cent) were male
      and 113 (64.6 per cent) were female, with a mean age at presentation of 36.4 +/-
      9.3 years (range: 19 to 78 years). The most common reasons for not offering LASIK
      were low corneal thickness (28.6 per cent), high myopia (15.4 per cent), large
      pupil (8.0 per cent) and keratoconus (7.4 per cent). Overall, 39 patients (22.3
      per cent) changed their mind after their initial consultations with surgeons. The
      prevalence of rejection of LASIK decreased from 44.1 per cent between July 2005
      and June 2006 to 3.5 per cent between July 2009 and June 2010. CONCLUSIONS:
      Reasons for not performing refractive surgery are quite diverse. Inadequate
      corneal thickness and change of mind after initial consultation were the most
      common reasons in the present study. There was a marked change in magnitude and
      trend of reasons for not performing LASIK over the study period. Further studies
      from settings other than university hospitals would be beneficial to compare the
      trend in patient selection.

PMID- 22607022
TI  - Genome-wide association study identified three major QTL for carcass weight
      including the PLAG1-CHCHD7 QTN for stature in Japanese Black cattle.
AB  - BACKGROUND: Significant quantitative trait loci (QTL) for carcass weight were
      previously mapped on several chromosomes in Japanese Black half-sib families. Two
      QTL, CW-1 and CW-2, were narrowed down to 1.1-Mb and 591-kb regions,
      respectively. Recent advances in genomic tools allowed us to perform a genome
      wide association study (GWAS) in cattle to detect associations in a general
      population and estimate their effect size. Here, we performed a GWAS for carcass
      weight using 1156 Japanese Black steers. RESULTS: Bonferroni-corrected genome
      wide significant associations were detected in three chromosomal regions on
      bovine chromosomes (BTA) 6, 8, and 14. The associated single nucleotide
      polymorphisms (SNP) on BTA 6 were in linkage disequilibrium with the SNP encoding
      NCAPG Ile442Met, which was previously identified as a candidate quantitative
      trait nucleotide for CW-2. In contrast, the most highly associated SNP on BTA 14
      was located 2.3-Mb centromeric from the previously identified CW-1 region.
      Linkage disequilibrium mapping led to a revision of the CW-1 region within a 0.9
      Mb interval around the associated SNP, and targeted resequencing followed by
      association analysis highlighted the quantitative trait nucleotides for bovine
      stature in the PLAG1-CHCHD7 intergenic region. The association on BTA 8 was
      accounted for by two SNP on the BovineSNP50 BeadChip and corresponded to CW-3,
      which was simultaneously detected by linkage analyses using half-sib families.
      The allele substitution effects of CW-1, CW-2, and CW-3 were 28.4, 35.3, and 35.0
      kg per allele, respectively. CONCLUSION: The GWAS revealed the genetic
      architecture underlying carcass weight variation in Japanese Black cattle in
      which three major QTL accounted for approximately one-third of the genetic
      variance.

PMID- 22607023
TI  - Mobility of Xe atoms within the oxygen diffusion channel of cytochrome ba(3)
      oxidase.
AB  - We use a form of "freeze-trap, kinetic crystallography" to explore the migration
      of Xe atoms away from the dinuclear heme a(3)/Cu(B) center in Thermus
      thermophilus cytochrome ba(3) oxidase. This enzyme is a member of the heme-copper
      oxidase superfamily and is thus crucial for dioxygen-dependent life. The
      mechanisms involved in the migration of oxygen, water, electrons, and protons
      into and/or out of the specialized channels of the heme-copper oxidases are
      generally not well understood. Pressurization of crystals with Xe gas previously
      revealed a O(2) diffusion channel in cytochrome ba(3) oxidase that is continuous,
      Y-shaped, 18-20 A in length and comprised of hydrophobic residues, connecting the
      protein surface within the bilayer to the a(3)-Cu(B) center in the active site.
      To understand movement of gas molecules within the O(2) channel, we performed
      crystallographic analysis of 19 Xe laden crystals freeze-trapped in liquid
      nitrogen at selected times between 0 and 480 s while undergoing outgassing at
      room temperature. Variation in Xe crystallographic occupancy at five discrete
      sites as a function of time leads to a kinetic model revealing relative degrees
      of mobility of Xe atoms within the channel. Xe egress occurs primarily through
      the channel formed by the Xe1 -> Xe5 -> Xe3 -> Xe4 sites, suggesting that ingress
      of O(2) is likely to occur by the reverse of this process. The channel itself
      appears not to undergo significant structural changes during Xe migration,
      thereby indicating a passive role in this important physiological function.

PMID- 22607025
TI  - Dynamic stability requirements during gait and standing exergames on the wii
      fit(r) system in the elderly.
AB  - BACKGROUND: In rehabilitation, training intensity is usually adapted to optimize
      the trained system to attain better performance (overload principle). However, in
      balance rehabilitation, the level of intensity required during training exercises
      to optimize improvement in balance has rarely been studied, probably due to the
      difficulty in quantifying the stability level during these exercises. The goal of
      the present study was to test whether the stabilizing/destabilizing forces model
      could be used to analyze how stability is challenged during several exergames,
      that are more and more used in balance rehabilitation, and a dynamic functional
      task, such as gait. METHODS: Seven healthy older adults were evaluated with three
      dimensional motion analysis during gait at natural and fast speed, and during
      three balance exergames (50/50 Challenge, Ski Slalom and Soccer). Mean and
      extreme values for stabilizing force, destabilizing force and the ratio of the
      two forces (stability index) were computed from kinematic and kinetic data to
      determine the mean and least level of dynamic, postural and overall balance
      stability, respectively. RESULTS: Mean postural stability was lower (lower mean
      destabilizing force) during the 50/50 Challenge game than during all the other
      tasks, but peak postural instability moments were less challenging during this
      game than during any of the other tasks, as shown by the minimum destabilizing
      force values. Dynamic stability was progressively more challenged (higher mean
      and maximum stabilizing force) from the 50/50 Challenge to the Soccer and Slalom
      games, to the natural gait speed task and to the fast gait speed task, increasing
      the overall stability difficulty (mean and minimum stability index) in the same
      manner. CONCLUSIONS: The stabilizing/destabilizing forces model can be used to
      rate the level of balance requirements during different tasks such as gait or
      exergames. The results of our study showed that postural stability did not differ
      much between the evaluated tasks (except for the 50/50 Challenge), compared to
      dynamic stability, which was significantly less challenged during the games than
      during the functional tasks. Games with greater centre of mass displacements and
      changes in the base of support are likely to stimulate balance control enough to
      see improvements in balance during dynamic functional tasks, and could be tested
      in pathological populations with the approach used here.

PMID- 22607026
TI  - Collapsed Cu(II)-hydroxamate metallacrowns.
AB  - Degradation of a strained, thermodynamically destabilized pentanuclear copper(II)
      12-metallacrown-4 complex based on a picoline hydroxamic acid resulted in the
      formation of the tetranuclear compounds which are the first examples of solely
      hydroxamate-based Cu(II) metallacrown complexes with a collapse of the
      metallamacrocyclic cavity.

PMID- 22607024
TI  - TGFB1 genetic polymorphisms and coronary heart disease risk: a meta-analysis.
AB  - BACKGROUND: Genetic variations in TGFB1 gene have been studied in relation to
      coronary heart disease (CHD) risk, but the results were inconsistent. METHODS: We
      performed a systematic review of published studies on the potential role of TGFB1
      genetic variation in CHD risk. Articles that reported the association of TGFB1
      genetic variants with CHD as primary outcome were searched via Medline and HuGE
      Navigator through July 2011. The reference lists from included articles were also
      reviewed. RESULTS: Data were available from 4 studies involving 1777 cases and
      7172 controls for rs1800468, 7 studies involving 5935 cases and 10677 controls
      for rs1800469, 7 studies involving 6634 cases and 9620 controls for rs1982073, 5
      studies involving 5452 cases and 9999 controls for rs1800471, and 4 studies
      involving 5143 cases and 4229 controls for rs1800472. The pooled odds ratios
      (ORs) for CHD among minor T allele carriers of rs1800469, minor C allele carriers
      of rs1982073, and minor C allele carriers of rs1800471 versus homozygous major
      allele carriers was 1.14 (95% confidence interval [CI]: 1.05-1.24), 1.18 (95% CI:
      1.04-1.35), and 1.16 (95% CI: 1.02-1.32), respectively. No substantial
      heterogeneity for ORs was detected among the included Caucasian populations for
      all SNPs. However, for rs1800471, the statistical significance disappeared after
      adjusting for potential publication bias. No significant association was found
      between rs1800468 and rs1800472 variants and CHD risk. CONCLUSION: Minor allele
      carriers of two genetic variants (rs1800469 and rs1982073) in TGFB1 have a 15%
      increased risk of CHD.

PMID- 22607027
TI  - Socio-demographic and behavioural inequalities in the impact of dental pain among
      adults: a population-based study.
AB  - OBJECTIVES: To assess socio-demographic and behavioural inequalities in the
      impact of dental pain on daily activities, as well as to estimate the prevalence
      and intensity of dental pain. METHODS: A population-based cross-sectional study
      was carried out in Florianopolis, Southern Brazil, with 1720 adults aged 20-59
      years in 2009-2010. Interviews were performed at adults' households, which
      included socio-demographics and behavioural characteristics, such as smoking
      status and alcohol abuse, along with mental health, self-reported health, number
      of retained teeth, dental pain occurrence (including its intensity and its impact
      on daily life). The association between the impact of dental pain and the
      covariates was tested using multinomial logistic regression. RESULTS: The global
      prevalence of dental pain was 14.8% (95% CI, 12.9-16.7). Adjusted analysis showed
      that women, those who self-classified as dark-skinned Blacks, those with low
      family income, current smokers and those with common mental disorders reported a
      higher impact of dental pain than their counterparts. Among subjects reporting
      dental pain, 12.7% indicated the maximum intensity, whereas 6.0% had some daily
      activity disrupted by it, such as difficulties in chewing certain foods (38.0%),
      sleep disturbance (21.0%), difficulty to work (21.0%) and difficulty in
      performing household tasks (8.0%). Prevalence ratios of impact of dental pain
      between the poorest income group and richest income group (2.4), between the
      highest and lowest schooling group (2.6), and between dark-skinned Blacks and
      Whites (2.1) were of higher magnitude than the dental pain prevalence ratios
      among the same groups (1.7, 1.3 and 1.4, respectively). CONCLUSIONS: The impact
      of dental pain showed a social gradient. Inequalities between socio-economic
      groups found in this study should be taken into account, as the impact of dental
      pain leads to reduced daily activities and poor quality of life.

PMID- 22607028
TI  - Translation and validation of the EORTC brain cancer module (EORTC QLQ-BN20) for
      use in Iran.
AB  - BACKGROUND: The aim of this study was to translate the EORTC quality of life
      questionnaire for brain cancer, the QLQ-BN20, into Persian, and to evaluate its
      psychometric properties when used among brain cancer patients in Iran. METHODS: A
      standard backward and forward translation procedure was used to generate the
      Persian language version of the QLQ-BN20. The QLQ-BN20 was administered together
      with the QLQ-C30 to 194 patients diagnosed with primary brain cancer. Multitrait
      scaling and confirmatory factor analysis (CFA) were used to evaluate the
      hypothesized scale structure of the questionnaire. Internal consistency
      reliability was estimated with Cronbach's alpha. The ability of the QLQ-BN20 to
      distinguish between patient subgroups formed on the basis of performance status
      and cognitive status was evaluated, as was the responsiveness of the
      questionnaire to changes in performance status over time. RESULTS: Multitrait
      scaling and CFA results confirmed the hypothesized scale structure. The
      measurement model was consistent across men and women. Internal consistency
      reliability of the multi-item scales ranged from 0.74 to 0.89. The QLQ-BN20
      distinguished clearly between patients with relatively good versus poor
      performance and cognitive status, and changes in scores over time reflected
      changes observed in performance status ratings. CONCLUSIONS: These results
      support the validity and reliability of the QLQ-BN20 for use among Iranian
      patients diagnosed with primary brain cancer. Future studies should examine the
      psychometrics of the questionnaire when used in patients with brain metastasis.

PMID- 22607029
TI  - Silver-catalyzed formal inverse electron-demand Diels-Alder reaction of 1,2
      diazines and siloxy alkynes.
AB  - A highly effective silver-catalyzed formal inverse electron-demand Diels-Alder
      reaction of 1,2-diazines and siloxy alkynes has been developed. The reactions
      provide ready access to a wide range of siloxy naphthalenes and anthracenes,
      which are formed in good to high yields, under mild reaction conditions, using
      low catalyst loadings.

PMID- 22607030
TI  - Ontogeny of the cranial system in Laonastes aenigmamus.
AB  - Rodents, together with bats, are among the ecologically most diverse and most
      speciose groups of mammals. Moreover, rodents show elaborate specializations of
      the feeding apparatus in response to the predominantly fore-aft movements of the
      lower jaw. The Laotian rock rat Laonastes aenigmamus was recently discovered and
      originally thought to belong to a new family. The difficulties in classifying L.
      aenigmamus based on morphological characters stem from the fact that it presents
      a mixture of sciurognathous and hystricognathous characteristics, including the
      morphology of the jaw adductors. The origin of the unusual muscular organization
      in this species remains, however, unclear. Here, we investigate the development
      of the masticatory system in Laonastes to better understand the origin of its
      derived morphology relative to other rodents. Our analyses show that skull and
      mandible development is characterized by an overall elongation of the snout
      region. Muscle mass increases with positive allometry during development and
      growth, and so does the force-generating capacity of the jaw adductor muscles
      (i.e. physiological cross-sectional area). Whereas fetal crania and musculature
      are more similar to those of typical rodents, adults diverge in the elongation of
      the rostral part of the skull and the disproportionate development of the
      zygomaticomandibularis. Our data suggest a functional signal in the development
      of the unusual cranial morphology, possibly associated with the folivorous
      trophic ecology of the species.

PMID- 22607031
TI  - BAR expressolog identification: expression profile similarity ranking of
      homologous genes in plant species.
AB  - Large numbers of sequences are now readily available for many plant species,
      allowing easy identification of homologous genes. However, orthologous gene
      identification across multiple species is made difficult by evolutionary events
      such as whole-genome or segmental duplications. Several developmental atlases of
      gene expression have been produced in the past couple of years, and it may be
      possible to use these transcript abundance data to refine ortholog predictions.
      In this study, clusters of homologous genes between seven plant species -
      Arabidopsis, soybean, Medicago truncatula, poplar, barley, maize and rice - were
      identified. Following this, a pipeline to rank homologs within gene clusters by
      both sequence and expression profile similarity was devised by determining
      equivalent tissues between species, with the best expression profile match being
      termed the 'expressolog'. Five electronic fluorescent pictograph (eFP) browsers
      were produced as part of this effort, to aid in visualization of gene expression
      data and to complement existing eFP browsers at the Bio-Array Resource (BAR).
      Within the eFP browser framework, these expression profile similarity rankings
      were incorporated into an Expressolog Tree Viewer to allow cross-species homolog
      browsing by both sequence and expression pattern similarity. Global analyses
      showed that orthologs with the highest sequence similarity do not necessarily
      exhibit the highest expression pattern similarity. Other orthologs may show
      different expression patterns, indicating that such genes may require re
      annotation or more specific annotation. Ultimately, it is envisaged that this
      pipeline will aid in improvement of the functional annotation of genes and
      translational plant research.

PMID- 22607032
TI  - Rab6-mediated retrograde transport regulates inner nuclear membrane targeting of
      caveolin-2 in response to insulin.
AB  - Here, we have identified a retrograde transport pathway of caveolin-2 (cav-2) for
      its regulatory function in the nucleus. Confocal microscopy analysis,
      photoactivation experiments and subcellular fractionation revealed that cav-2
      localized in the Golgi was transported to the inner nuclear membrane (INM) in
      response to insulin. Exogenous caveolin-1 (cav-1) and P132L-cav-1 expression did
      not affect the Golgi localization and insulin-induced INM targeting of cav-2. Cav
      2(DKV)  mutant in the endoplasmic reticulum (ER) was unable to translocate to the
      INM in response to insulin. The GTP-bound form of Rab6 promoted, but Rab6 siRNA
      and the GDP-bound form of Rab6 abrogated, retrograde trafficking of cav-2 from
      the Golgi to ER. Colchicine or nocodazole treatment abolished insulin-induced INM
      targeting of cav-2. Knock down of gp210 inhibited insulin-induced import of cav-2
      from ER/outer nuclear membrane (ONM) to the INM. The INM-targeted cav-2 prevented
      heterochromatinization and promoted transcriptional activation of Elk-1 and
      signal transducer and activator of transcription 3 (STAT3). The results provide
      molecular mechanisms for insulin-induced INM translocation of cav-2 initiated (i)
      by Golgi-to-ER retrograde trafficking of cav-2 via microtubule-based Rab6-GTP
      dependent transport and subsequently processed (ii) by gp210-mediated import of
      cav-2 from ER/ONM to INM.

PMID- 22607033
TI  - Sedative effects of dexmedetomidine, dexmedetomidine-pethidine and
      dexmedetomidine-butorphanol in cats.
AB  - The purpose of this study was to assess the clinical effects of dexmedetomidine,
      both alone and combined with pethidine or butorphanol, in cats. A prospective
      randomized blind study was performed. Thirty cats were randomly assigned to three
      groups of 10 animals: D: dexmedetomidine (20 MUg/kg IM); DP: dexmedetomidine (10
      MUg/kg IM) and pethidine (2.5 mg/kg IM); DB: dexmedetomidine (10 MUg/kg IM) and
      butorphanol (0.4 mg/kg IM). Quality of sedation, analgesia, muscle relaxation and
      the possibility of performing some clinical procedures were compared using a
      multifactorial scale. Sedation, analgesia and muscle relaxation increased
      progressively over time and did not differ in the three protocols. The three
      protocols facilitated the completion of several clinical procedures. The clinical
      variables studied showed a similar behaviour in the three protocols and remained
      close to the baseline, except for a drop in heart rate in protocol D. In
      conclusion, dexmedetomidine, either alone or combined with pethidine or
      butorphanol, offers suitable sedation, analgesia and relaxation to perform
      various clinical procedures in cats.

PMID- 22607034
TI  - The decision-making process for the fate of frozen embryos by Japanese infertile
      women: a qualitative study.
AB  - BACKGROUND: Previous studies have found that the decision-making process for
      stored unused frozen embryos involves much emotional burden influenced by socio
      cultural factors. This study aims to ascertain how Japanese patients make a
      decision on the fate of their frozen embryos: whether to continue storage discard
      or donate to research. METHODS: Ten Japanese women who continued storage, 5 who
      discarded and 16 who donated to research were recruited from our infertility
      clinic. Tape-recorded interviews were transcribed and analyzed for emergent
      themes. RESULTS: A model of patients' decision-making processes for the fate of
      frozen embryos was developed, with a common emergent theme, "coming to terms with
      infertility" resulting in either acceptance or postponing acceptance of their
      infertility. The model consisted of 5 steps: 1) the embryo-transfer moratorium
      was sustained, 2) the "Mottainai"- embryo and having another child were
      considered; 3) cost reasonability was taken into account; 4) partner's opinion
      was confirmed to finally decide whether to continue or discontinue storage. Those
      discontinuing, then contemplated 5): the effect of donation. Great emotional
      conflict was expressed in the theme, steps 2, 4, and 5. CONCLUSIONS: Patients' 5
      step decision-making process for the fate of frozen embryos was profoundly
      affected by various Japanese cultural values and moral standards. At the end of
      their decision, patients used culturally inherent values and standards to come to
      terms with their infertility. While there is much philosophical discussion on the
      moral status of the embryo worldwide, this study, with actual views of patients
      who own them, will make a significant contribution to empirical ethics from the
      practical viewpoint.

PMID- 22607035
TI  - Pyrazolopyridines as inhibitors of the kinase LRRK2: a patent evaluation
      (WO2011141756).
AB  - Scientific evaluation of a patent aiming for the development of pyrazolopyridine
      derivatives as LRRK2 kinase inhibitors, a potential therapeutic target for
      combating Parkinson's disease.

PMID- 22607036
TI  - Clinical characteristics differ considerably between phenotypes of bladder pain
      syndrome/interstitial cystitis.
AB  - OBJECTIVE: Bladder pain syndrome/interstitial cystitis (BPS/IC) is one of the
      most bothersome conditions in urological practice. This syndrome includes a
      heterogeneous collection of underlying pathological conditions. Compared to the
      classic IC with a Hunner lesion, now denominated European Society for the Study
      of Interstitial Cystitis (ESSIC) type 3C, the non-Hunner type of BPS/IC appears
      different concerning demographic, endoscopic and histological findings, as well
      as the response to all forms of treatment. The objective of this study was to
      determine whether there are additional dissimilarities in clinical presentation
      between the main phenotypes of BPS/IC. MATERIAL AND METHODS: In total, 393 BPS/IC
      patients (210 type 3C and 183 non-Hunner), diagnosed according to National
      Institute of Diabetes and Digestive and Kidney Diseases and ESSIC criteria, were
      studied by surveying the clinical records including micturition diaries. RESULTS:
      In this clinical material, BPS/IC ESSIC type 3C accounted for 55% of cases.
      Patients with non-Hunner disease were on average 20 years younger at the time of
      diagnosis. Furthermore, there was a marked and significant difference in bladder
      capacity under general anaesthesia (p < 0.0001). CONCLUSIONS: The findings in the
      present series, together with previously published reports by this group and by
      others, confirm the striking differences between the main forms of BPS/IC and
      underline the indispensability of adequate subtyping in clinical studies.

PMID- 22607037
TI  - Redox proteomics in study of kidney-associated hypertension: new insights to old
      diseases.
AB  - SIGNIFICANCE: The kidney helps to maintain low blood pressure in the human body,
      and impaired kidney function is a common attribute of aging that is often
      associated with high blood pressure (hypertension). Kidney-related pathologies
      are important contributors (either directly or indirectly) to overall human
      mortality. In comparison with other organs, kidney has an unusually wide range of
      oxidative status, ranging from the well-perfused cortex to near-anoxic medulla.
      RECENT ADVANCES: Oxidative stress has been implicated in many kidney pathologies,
      especially chronic kidney disease, and there is considerable research interest in
      oxidative stress biomarkers for earlier prediction of disease onset. Proteomics
      approaches have been taken to study of human kidney tissue, serum/plasma, urine,
      and animal models of hypertension. CRITICAL ISSUES: Redox proteomics, in which
      oxidative post-translational modifications can be identified in protein targets
      of oxidative or nitrosative stress, has not been very extensively pursued in this
      set of pathologies. FUTURE DIRECTIONS: Proteomics studies of kidney and related
      tissues have relevance to chronic kidney disease, and redox proteomics, in
      particular, represents an under-exploited toolkit for identification of novel
      biomarkers in this commonly occurring pathology.

PMID- 22607038
TI  - Nurses' competence in genetics: a mixed method systematic review.
AB  - AIM:   To ascertain the extent to which nurses are achieving the core competences
      in genetics appropriate for nursing practice. BACKGROUND:   There is an
      increasing focus on genetics in nursing, and relevant core competences have been
      developed. However, it is unclear whether nurses are achieving these competences.
      DATA SOURCES:   Four databases (CINAHL, Medline, The Allied and Complementary
      Medicine Database, and British Nursing Index) were searched. Hand searching of
      relevant reference lists and author names was also conducted. DESIGN: Systematic
      review. REVIEW METHODS:   The systematic review was undertaken using methods
      described by the Centre for Reviews and Dissemination (University of York, 2008).
      Research studies published in English between January 2000-January 2011 reporting
      data focussing on nurse competence in genetics were eligible for inclusion. Data
      were abstracted for inclusion in a table and subjected to thematic analysis: due
      to diversity of studies, a meta-analysis was not performed. RESULTS:   Of 269
      papers retrieved, 13 were eligible for inclusion. There were five main themes:
      knowledge, experience in using skills, ethical practice, perceived relevance, and
      confidence. Although the majority of participants believed genetics was relevant
      to their role, their knowledge of genetic concepts was generally poor; however,
      most studies measured self-reported knowledge rather than assessing actual
      knowledge. CONCLUSIONS:   There is little evidence on this topic, but it does
      appear from the available evidence that nurses are not demonstrating the
      competences needed to offer holistic health care to people with genetic
      conditions. Pre- and post-registration programmes must be enhanced to include
      genetic health care.

PMID- 22607039
TI  - Flexible generation of gradient electrospinning nanofibers using a microfluidic
      assisted approach.
AB  - The nanofiber surface modified with physical or chemical gradients is very useful
      in a wide range of areas including tissue engineering, regenerative medicine,
      drug screening, and biomaterial chemistry. In this work, we presented a novel and
      straightforward microfluidic assisted approach to produce electrospinning
      nanofibers containing gradients in different compositions, nanoparticles and
      biomolecule concentrations. The series of gradient nanofibers were mainly
      produced by using a two inlet microfluidic device in combination with an
      electrospinning nozzle on a 3-D controllable platform, which exhibited different
      functions and properties. The controlled nanofibers with incorporated biomolecule
      gradient were used for guiding the spatial differentiation in mesenchymal stem
      cells (MSCs). This established approach is very simple, and flexible to operate,
      which might find enormous potential for biology and tissue engineering
      applications.

PMID- 22607040
TI  - Angiotensin-converting enzyme (ACE) gene II genotype protects against the
      development of diabetic peripheral neuropathy in type 2 diabetes mellitus.
AB  - BACKGROUND:   Diabetic peripheral neuropathy (DPN) is one of the complications of
      type 2 diabetes mellitus (T2DM) that decreases the quality of life of T2DM
      patients. Very few studies have found an association between the development and
      progression of DPN in T2DM and angiotensin-converting enzyme (ACE) gene
      insertion/deletion (I/D) polymorphisms. METHODS:   Using gene-specific primers in
      a polymerase chain reaction, the presence of ACE I/D polymorphisms was screened
      for in 276 T2DM patients with DPN, 496 T2DM patients without DPN, and 331 control
      (non-diabetic) subjects. RESULTS:   The distribution of the I/D genotypes was in
      Hardy-Weinberg equilibrium. The II genotype was significantly more prevalent in
      T2DM patients without DPN than the DD genotype (P < 0.05); however, there was no
      significant difference in the prevalence of the II and DD genotypes in T2DM
      patients with DPN (P = 0.78). CONCLUSION:   The II genotype of the ACE gene has a
      protective effect against the development of DPN in T2DM patients. This suggests
      a role for the renin-angiotensin system in modulating neuropathy in T2DM.

PMID- 22607041
TI  - Limited overall survival in patients with brain metastases from triple negative
      breast cancer.
AB  - Patients with breast cancer, which lacks ER, PR, and HER2; "triple negative"
      (TNBC), are at increased risk of brain metastases (BMs). However, the impact of
      modern therapy on the risk of BMs and outcomes remains largely unknown. In this
      retrospective, single-institution study we assessed the incidence of BMs, the
      therapeutic options, and overall survival, in a recent cohort of patients with
      TNBC. Women diagnosed with early stage TNBC from January 1, 1998 to December 31,
      2007 were identified through institutional databases. Electronic medical records
      were reviewed to assess patterns of recurrence, treatment, and survival. In
      total, 1,323 patients, median age 53 years (range 20-91), were identified. There
      were 298 patients (23%) who developed metastatic disease, of whom, 99 (33%)
      developed BMs, representing 7.5% of the entire cohort. Following BM diagnosis,
      treatment consisted of: radiotherapy 87 (88%) patients, resection 26 (26%)
      patients, and systemic chemotherapy 70 (71%) patients, with a median of 1.0
      (range 0-8) chemotherapy regimens. The actuarial median survival from diagnosis
      of BMs is 5 months (95% CI 4-7 months). This single-institution, retrospective
      study confirms that the prognosis for patients with BMs from TNBC remains poor.
      This group of patients urgently needs improved therapies.

PMID- 22607042
TI  - A unified framework for haplotype inference in nuclear families.
AB  - Many large genome-wide association studies include nuclear families with more
      than one child (trio families), allowing for analysis of differences between
      siblings (sib pair analysis). Statistical power can be increased when haplotypes
      are used instead of genotypes. Currently, haplotype inference in families with
      more than one child can be performed either using the familial information or
      statistical information derived from the population samples but not both.
      Building on our recently proposed tree-based deterministic framework (TDS) for
      trio families, we augment its applicability to general nuclear families. We
      impose a minimum recombinant approach locally and independently on each multiple
      children family, while resorting to the population-derived information to solve
      the remaining ambiguities. Thus our framework incorporates all available
      information (familial and population) in a given study. We demonstrate that using
      all the constraints in our approach we can have gains in the accuracy as opposed
      to breaking the multiple children families to separate trios and resorting to a
      trio inference algorithm or phasing each family in isolation. We believe that our
      proposed framework could be the method of choice for haplotype inference in
      studies that include nuclear families with multiple children. Our software
      (tds2.0) is downloadable from www.ee.columbia.edu/~anastas/tds.

PMID- 22607043
TI  - The pharmacodynamics of vecuronium in chronic renal failure patients: the impact
      of different priming doses.
AB  - PURPOSE: The concept of priming was introduced to facilitate a faster onset of
      nondepolarizing neuromuscular blocker for endotracheal intubation. Vecuronium is
      still very much in use for most chronic renal failure patients posted for renal
      transplantation. The aim of this study was to examine the pharmacodynamics of
      vecuronium without and with preceding different small doses. METHODS: One hundred
      chronic renal failure patients were assigned into four groups according to the
      used vecuronium priming regimen. The first control group (V(0)-group), where no
      priming dose was given. The other three priming groups (V(10)- , V(15)- , and
      V(20)-groups), where 10%, 15%, and 20% of ED(95) of vecuronium were administrated
      5 min prior to the remaining intubating dose (2 * ED(95)) of vecuronium.
      Neuromuscular blockade was measured via acceleromyographic response of the ulnar
      nerve. Train-of-four (TOF) ratio was measured every minute during priming
      interval. Any unpleasant symptoms during precurarization were recorded. Lag time
      and onset time (from injection of intubating dose) were recorded. Endotracheal
      intubation condition was scored blindly. The duration and recovery times were
      also recorded. RESULTS: The significant higher incidence of symptoms of paresis
      was encountered in V(20)-group in comparison with other two priming groups. TOF
      ratio started to decrease significantly at the first minute in V(20)-group, at
      the second minute in V(15)-group, and at the third minute in V(10)-group, till
      the fourth minute in the priming interval. Although TOF ratio was still above
      0.90 in V(10)-group, it was below 0.80 in V(20)-group. Priming groups did not
      show significant intergroup difference in onset time. However, duration and
      recovery times were significantly longer in priming groups in comparison with
      V(0)-group without priming. CONCLUSION: Priming the chronic renal failure
      patients with 10% of ED(95) vecuronium dose acquit the best pharmacodynamics with
      the fewest signs of muscle weakness. Larger vecuronium priming doses are
      unfavorable and convey no more clinical utility.

PMID- 22607044
TI  - Application of a fluorescent C-linked phenolic purine adduct for selective N7
      metalation of DNA.
AB  - The C-linked phenolic adduct, C8-(2"-hydroxyphenyl)-2'-deoxyguanosine (o-PhOHdG),
      has been employed to study the impact of N7-metalation of 2'-deoxyguanosine (dG)
      within duplex DNA. The phenolic group of o-PhOHdG assists selective metal ion
      coordination by the N7-site of the attached dG moiety, which is the most
      important metal binding site in duplex DNA. The biaryl nucleobase probe o-PhOHdG
      is highly fluorescent in water (Phi(fl) = 0.44), and changes in its absorption
      and emission were used to determine apparent association constants (K(a)) for
      binding to Cu(II), Ni(II), and Zn(II). The nucleoside was found to bind Cu(II)
      (log K(a) = 4.59) and Ni(II) (log K(a) = 3.65) effectively, but it showed
      relatively poor affinity for Zn(II) (log K(a) = 2.55). The fluorescent nucleobase
      o-PhOHdG was incorporated into a pyrimidine-rich oligonucleotide substrate (ODN1)
      and a purine-rich (ODN2) substrate to monitor selective binding of Cu(II) through
      fluorescence quenching of the enol emission of o-PhOHdG within the DNA
      substrates. The pyrimidine-rich substrate ODN1 was found to possess greater
      affinity for Cu(II) than the free nucleobase, while the purine-rich substrate
      ODN2 exhibited diminished Cu(II) binding affinity. The impact of Cu(II) on duplex
      stability and structure was determined using UV melting temperature analysis and
      circular dichroism (CD) measurements. These studies highlight the syn preference
      for Cu(II)-bound o-PhOHdG within ODN1 duplexes and demonstrate competitive Cu(II)
      binding by other natural dG nucleobases within ODN2. The metal binding properties
      of o-PhOHdG are compared to the structurally similar 2-(2'
      hydroxyphenyl)benzoxazole (HBO) derivatives and the nucleoside C8-(2-pyridyl)-dG
      (2PydG) that has also been used to control N7-metal coordination in DNA. Our
      results show certain advantages to the use of o-PhOHdG that stem from its highly
      fluorescent nature in aqueous media and provide additional tools for studying the
      effects of N7-metalation on the structure and stability of duplex DNA.

PMID- 22607045
TI  - Coronary artery bypass grafting for myocardial bridges of the left anterior
      descending artery.
AB  - BACKGROUND AND AIM OF THE STUDY: There is still controversy with regard to
      adequate therapy for symptomatic patients who are refractory to medical
      management with myocardial bridges of the left anterior descending artery. This
      study sought to evaluate the treatment of symptomatic coronary myocardial bridges
      with coronary artery bypass graft surgery. METHODS: Thirteen patients who
      underwent surgery between October 2005 and May 2008 were included in this study.
      The mean patient age was 51.3 +/- 10.2 years (range, 39-75 years). There were ten
      men and three women. All 13 patients had angina pectoris preoperatively, and they
      had myocardial bridges only. Coronary angiography prior to surgery demonstrated
      myocardial bridging of the left anterior descending artery with systolic
      compression >=75% in all patients. They underwent off-pump coronary artery bypass
      grafting using the internal mammary artery. RESULTS: The acute clinical success
      rate was 100% with respect to the absence of myocardial infarction, death, or
      other major in-hospital complications. Postoperative coronary CT angiography
      studies in seven patients after one year demonstrated no graft stenosis. During
      follow-up, no patient had symptoms of angina. CONCLUSIONS: Coronary artery bypass
      graft surgery using a LIMA graft is a safe and effective treatment for
      symptomatic coronary myocardial bridges.

PMID- 22607046
TI  - Development and comparative evaluation of in vitro, in vivo properties of novel
      controlled release compositions of paroxetine hydrochloride hemihydrate as
      against GeomatrixTM platform technology.
AB  - The objective of this study is to develop, in vitro and in vivo evaluation of
      novel approaches for controlled release of paroxetine hydrochloride hemihydrate
      (PHH) in comparison to patented formulation PAXIL CR((r)) tablets of
      GlaxoSmithKline (GeomatrixTM technology). In one of the approaches, hydrophilic
      core matrix tablets containing 85% of the dose were prepared and further coated
      with methacrylic acid copolymer to delay the release. An immediate release
      coating of 15% was given as top coat. The tablets were further optionally coated
      using ethyl cellulose. In the second approach, hydrophobic matrix core tablets
      containing metharylic acid copolymer were prepared. In the third approach, PHH
      was granulated with enteric polymer and further hydrophobic matrix core tablets
      were prepared. The effect of polymer concentration, level of enteric coating on
      drug release was evaluated by in vitro dissolution study by varying dissolution
      apparatus and the rotation speeds. It was found that increase in concentration of
      high viscosity hydroxypropylmethylcellulose (HPMC) resulted in reduction of the
      release rate. The drug release was observed to be dependent on the level of
      enteric coating and ethyl cellulose coating, being slower at increased coating.
      The release mechanism of PHH followed zero-order shifting to dissolution
      dependent by the increase of HPMC content. The formulation was stable without
      change in drug release rate. In vivo study in human volunteers confirmed the
      similarity between test and innovator formulations. In conclusion, HPMC-based
      matrix tablets, which were further coated using methacrylic acid copolymer, were
      found to be suitable for the formulation of single layer-controlled release PHH. 

PMID- 22607047
TI  - Urinary protein markers predict the severity of renal histological lesions in
      children with mesangial proliferative glomerulonephritis.
AB  - BACKGROUND: Several renal histopathological features, including mesangial
      hypercellularity, glomerulosclerosis, tubular atrophy and interstitial fibrosis,
      are considered to be independent predictors of end-stage renal failure in
      patients with glomerular diseases. Mesangial proliferative glomerulonephritis
      (MesPGN) is characterized by proliferations of mesangial cells with increase in
      mesangial matrix and/or deposits in mesangial region. The purpose of this study
      is to determine the association between urinary protein markers measured at the
      same time as renal biopsy and the severity of renal histological lesions in
      children with MesPGN, and to evaluate whether these markers could serve as
      predictors of severe renal histological lesions in this population. METHODS:
      Ninety-eight children with MesPGN (40 with IgA nephropathy, 37 with IgM
      nephropathy, and 21 with MesPGN without IgA/IgM deposition) were enrolled.
      Urinary level of IgG, albumin, transferrin, alpha1-microglobulin, beta2
      microglobulin and N-acetyl-beta-glucosaminidase from a morning sample before
      biopsy was measured.The scores of mesangial hypercellularity, glomerulosclerosis,
      and tubule-interstitial damage were used to semi-quantitatively evaluate renal
      histological lesions. RESULTS: The urine proteins, as independent factors
      associated with severe mesangial cellularity (> 5 mesangial cells/ mesangial
      area) were transferrin, albumin, alpha1-microglobulin, IgG and 24-hour total
      protein, with severe glomerulosclerosis (>= 10 % glomeruli showing segmental
      adhesions or sclerosis) were transferrin and 24-hour total protein, and with
      severe tubule-interstitial damage (focal or diffuse tubular and interstitial
      lesions) were transferrin and N-acetyl-beta-glucosaminidase. Urinary transferrin
      achieved the area under-the-receiver-operating-characteristic curve (AUC) of 0.86
      and 0.82, respectively, for predicting severe mesangial cellularity and
      glomerulosclerosis. Urinary N-acetyl-beta-glucosaminidase achieved the highest
      AUC of 0.82 for predicting severe tubule-interstitial damage. The combination of
      urinary protein markers, however, did not improve the predictability for renal
      histological lesions. CONCLUSIONS: Urinary protein markers are useful to predict
      the severity of renal histological lesions in children with MesPGN, which
      suggests that urinary proteins might be useful to predict the development and
      progression of renal histological lesions, and assist in evaluating the outcome
      and prognosis in children with MesPGN as non-invasive and easily repeatable
      indicators on the follow-up examination.

PMID- 22607048
TI  - Genome-wide linkage analysis of QTL for growth and body composition employing the
      PorcineSNP60 BeadChip.
AB  - BACKGROUND: The traditional strategy to map QTL is to use linkage analysis
      employing a limited number of markers. These analyses report wide QTL confidence
      intervals, making very difficult to identify the gene and polymorphisms
      underlying the QTL effects. The arrival of genome-wide panels of SNPs makes
      available thousands of markers increasing the information content and therefore
      the likelihood of detecting and fine mapping QTL regions. The aims of the current
      study are to confirm previous QTL regions for growth and body composition traits
      in different generations of an Iberian x Landrace intercross (IBMAP) and
      especially identify new ones with narrow confidence intervals by employing the
      PorcineSNP60 BeadChip in linkage analyses. RESULTS: Three generations (F3,
      Backcross 1 and Backcross 2) of the IBMAP and their related animals were
      genotyped with PorcineSNP60 BeadChip. A total of 8,417 SNPs equidistantly
      distributed across autosomes were selected after filtering by quality, position
      and frequency to perform the QTL scan. The joint and separate analyses of the
      different IBMAP generations allowed confirming QTL regions previously identified
      in chromosomes 4 and 6 as well as new ones mainly for backfat thickness in
      chromosomes 4, 5, 11, 14 and 17 and shoulder weight in chromosomes 1, 2, 9 and
      13; and many other to the chromosome-wide signification level. In addition, most
      of the detected QTLs displayed narrow confidence intervals, making easier the
      selection of positional candidate genes. CONCLUSIONS: The use of higher density
      of markers has allowed to confirm results obtained in previous QTL scans carried
      out with microsatellites. Moreover several new QTL regions have been now
      identified in regions probably not covered by markers in previous scans, most of
      these QTLs displayed narrow confidence intervals. Finally, prominent putative
      biological and positional candidate genes underlying those QTL effects are listed
      based on recent porcine genome annotation.

PMID- 22607049
TI  - Design, synthesis, and biological activities of some branched carbasugars:
      construction of a substituted 6-oxabicyclo[3.2.1]nonane skeleton.
AB  - Transformation of cyclohexa-2,4-diene-1,2-diylbis(methylene) diacetate to various
      carbasugars is described. Photooxygenation of a cyclohexadiene derivative gave a
      bicyclicendoperoxide, which was reduced with thiourea to [2
      [(acetyloxy)methyl]cyclohexa-2,4-dien-1-yl]methyl acetate. Epoxidation of the
      remaining double bond followed by epoxide ring-opening and hydrolysis of the
      acetate groups gave one of the target hexols. The bicyclic endoperoxide was
      rearranged to a diepoxide with CoTPP. The diepoxide was reacted with sulfamic
      acid in acetic anhydride, resulting in the formation of a new branched carbasugar
      as well as in the formation of cyclitols with a 6-oxabicyclo[3.2.1]nonane
      skeleton. The mechanism of the formation of the products is discussed. The
      inhibition activity of six cyclitol derivatives was tested against alpha
      glycosidase.

PMID- 22607050
TI  - Vitamin B12 deficiency in the brain leads to DNA hypomethylation in the
      TCblR/CD320 knockout mouse.
AB  - BACKGROUND: DNA methylation is an epigenetic phenomenon that can modulate gene
      function by up or downregulation of gene expression. Vitamin B12 and folate
      pathways are involved in the production of S-Adenosylmethionine, the universal
      methyl donor. FINDINGS: Brain vitamin B12 concentration and global DNA
      methylation was determined in transcobalamin receptor (TCblR/CD320) knock out
      (KO) (n = 4) and control mice (n = 4) at 20-24 weeks of age. Median [IQR] brain
      vitamin B12 concentrations (pg/mg) in TCblR/CD320 KO mice compared with control
      mice was 8.59 [0.52] vs 112.42 [33.12]; p < 0.05. Global DNA methylation levels
      in brain genomic DNA were lower in TCblR/CD320 KO compared with control mice
      (Median [IQR]: 0.31[0.16] % vs 0.55[0.15] %; p < 0.05.). CONCLUSIONS: In
      TCblR/CD320 KO mice, brain vitamin B12 drops precipitously by as much as 90%
      during a 20 week period. This decrease is associated with a 40% decrease in
      global DNA methylation in the brain. Future research will reveal whether the
      disruption in gene expression profiles due to changes in DNA hypomethylation
      contribute to central nervous system pathologies that are frequently seen in
      vitamin B12 deficiency.

PMID- 22607051
TI  - In situ SAXS study on a new mechanism for mesostructure formation of ordered
      mesoporous carbons: thermally induced self-assembly.
AB  - A new mechanism for mesostructure formation of ordered mesoporous carbons (OMCs)
      was investigated with in situ small-angle X-ray scattering (SAXS) measurements:
      thermally induced self-assembly. Unlike the well-established evaporation-induced
      self-assembly (EISA), the structure formation for organic-organic self-assembly
      of an oligomeric resol precursor and the block-copolymer templates Pluronic P123
      and F127 does not occur during evaporation but only by following a
      thermopolymerization step at temperatures above 100  degrees C. The systems
      investigated here were cubic (Im3m), orthorhombic Fmmm) and 2D-hexagonal (plane
      group p6mm) mesoporous carbon phases in confined environments, as thin films and
      within the pores of anodic alumina membranes (AAMs), respectively. The thin films
      were prepared by spin-coating mixtures of the resol precursor and the surfactants
      in ethanol followed by thermopolymerization of the precursor oligomers. The
      carbon phases within the pores of AAMs were made by imbibition of the latter
      solutions followed by solvent evaporation and thermopolymerization within the
      solid template. This thermopolymerization step was investigated in detail with in
      situ grazing incidence small-angle X-ray scattering (GISAXS, for films) and in
      situ SAXS (for AAMs). It was found that the structural evolution strongly depends
      on the chosen temperature, which controls both the rate of the mesostructure
      formation and the spatial dimensions of the resulting mesophase. Therefore the
      process of structure formation differs significantly from the known EISA process
      and may rather be viewed as thermally induced self-assembly. The complete process
      of structure formation, template removal, and shrinkage during carbonization up
      to 1100  degrees C was monitored in this in situ SAXS study.

PMID- 22607052
TI  - Rasch analysis of the Mini-Mental Adjustment to Cancer Scale (mini-MAC) among a
      heterogeneous sample of long-term cancer survivors: a cross-sectional study.
AB  - BACKGROUND: The mini-Mental Adjustment to Cancer Scale (mini-MAC) is a well
      recognised, popular measure of coping in psycho-oncology and assesses five cancer
      specific coping strategies. It has been suggested that these five subscales could
      be grouped to form the over-arching adaptive and maladptive coping subscales to
      facilitate the interpretation and clinical application of the scale. Despite the
      popularity of the mini-MAC, few studies have examined its psychometric properties
      among long-term cancer survivors, and further validation of the mini-MAC is
      needed to substantiate its use with the growing population of survivors.
      Therefore, this study examined the psychometric properties and dimensionality of
      the mini-MAC in a sample of long-term cancer survivors using Rasch analysis.
      METHODS: RUMM 2030 was used to analyse the mini-MAC data (n=851). Separate Rasch
      analyses were conducted for each of the original mini-MAC subscales as well as
      the over-arching adaptive and maladaptive coping subscales to examine summary and
      individual model fit statistics, person separation index (PSI), response format,
      local dependency, targeting, item bias (or differential item functioning -DIF),
      and dimensionality. RESULTS: For the fighting spirit, fatalism, and helplessness
      hopelessness subscales, a revised three-point response format seemed more optimal
      than the original four-point response. To achieve model fit, items were deleted
      from four of the five subscales - Anxious Preoccupation items 7, 25, and 29;
      Cognitive Avoidance items 11 and 17; Fighting Spirit item 18; and Helplessness
      Hopelessness items 16 and 20. For those subscales with sufficient items, analyses
      supported unidimensionality. Combining items to form the adaptive and maladaptive
      subscales was partially supported. CONCLUSIONS: The original five subscales
      required item deletion and/or rescaling to improve goodness of fit to the Rasch
      model. While evidence was found for overarching subscales of adaptive and
      maladaptive coping, extensive modifications were necessary to achieve this
      result. Further exploration and validation of over-arching subscales assessing
      adaptive and maladaptive coping is necessary with cancer survivors.

PMID- 22607053
TI  - The role of coaggregation between Porphyromonas gingivalis and Fusobacterium
      nucleatum on the host response to mixed infection.
AB  - AIM: To evaluate the role of coaggregation between Porphyromonas gingivalis and
      Fusobacterium nucleatum on the virulence of the mixed infection in mice.
      MATERIALS AND METHODS: Inhibition of coaggregation was carried out using lactose.
      In vitro, inhibition of coaggregation was verified using a coaggregation assay.
      In vivo, the virulence of the mixed infection, with and without coaggregation,
      was examined in a model of experimental periodontitis in mice. The local host
      response to the mixed infection, with or without coaggregation, was examined
      using the subcutaneous chamber model of infection. RESULTS: Lactose inhibited the
      coaggregation between P. gingivalis and F. nucleatum at all the tested
      concentrations (1-0.0625 M). Surprisingly, the addition of lactose to the mixed
      infection increased the severity of experimental periodontitis (as measured by
      alveolar bone loss) compared with mixed infection with coaggregating bacteria.
      The addition of lactose to the mixed infection resulted in mild attenuation of
      TNFalpha and IL-1beta levels. In addition, inhibition of coaggregation resulted
      in inhibition of the phagocytosis of F. nucleatum and augmentation of the
      phagocytosis of P. gingivalis. CONCLUSIONS: The ability of P. gingivalis and F.
      nucleatum to coaggregate may limit their ability to induce experimental
      periodontitis in a mixed infection model. Moreover, there is a shift in the
      phagocytosis pattern of the bacteria with the annulment of coaggregeaiton, with a
      reduction in F. nucleatum phagocytosis and amplification of P. gingivalis
      phagocytosis. The increased virulence of the mixed infection without
      coaggregation may surprisingly lay in the sustention of F. nucleatum in the
      infected sites.

PMID- 22607054
TI  - Daily vitamin E supplementation does not improve metabolic and glycemic control
      in type 2 diabetic patients: a double blinded randomized controlled trial.

PMID- 22607055
TI  - Adhesion, stretching, and electrical charge assessment of dermatan sulfate
      molecules by colloidal probes.
AB  - Electrical and mechanical properties of dermatan sulfate (DS) molecules are
      studied in an aqueous environment as a function of pH. DS molecules linked at
      various points distributed on the surface of mica previously silanizated along
      with a suitable functionalized microsphere, attached to the cantilever of an
      atomic force microscope (AFM), provided suitable surfaces for testing
      interactions through the colloidal probe methodology. The repulsive force between
      the surfaces indicated that the charge of DS increases with pH as a result of the
      gradual deprotonation of acidic groups. Pulling experiments revealed increasing
      adhesion of DS to the monolayer as a function of pH, presumably due both to the
      electrical nature of the interaction between these molecules and the progressive
      increase of the charge of DS with pH. Serrations exhibited by the force in
      pulling experiments indicate that more than a single DS molecule is stretched at
      the same time. In addition, pulling force remained significant even at extensions
      that went beyond the average contour length of a single DS molecule, which
      suggests the existence of a significant link between DS molecules.

PMID- 22607056
TI  - Evaluation of regional limb perfusion with amikacin using the saphenous,
      cephalic, and palmar digital veins in standing horses.
AB  - Previous studies have shown that regional limb perfusion (RLP) using the palmar
      digital (PD) vein delivers therapeutic concentration of amikacin to the distal
      limb. Our hypothesis was that using the cephalic and saphenous veins for RLP will
      enable delivery of therapeutic concentrations of amikacin to the distal limb.
      Nineteen healthy horses participated in the study. The cephalic, saphenous, or PD
      vein was used to perfuse the limb with amikacin. Two grams of amikacin was used
      for RLP using the saphenous and the cephalic veins, and one gram was used in the
      PD vein. Synovial samples were collected from the metacarpo-/metatarsophalangeal
      (MCP/MTP) joint, and blood samples were collected from the jugular vein. Maximum
      concentration (Cmax) of amikacin in the MCP/MTP joint using the cephalic and the
      saphenous vein was 277 and 363 mg/L, respectively. The amikacin concentrations
      achieved in the synovial fluid of the MCP/MTP joint in the current study were
      between 69 and 91 times the minimally inhibitory concentration of common
      susceptible bacterial pathogens causing orthopedic infections in horses. To
      conclude, this study shows that use of the proximal veins for RLP to treat distal
      limb infections is a viable alternative to using the palmar or plantar digital
      vein.

PMID- 22607057
TI  - Maintaining the 'good maternal body': expressing milk as a way of negotiating the
      demands and dilemmas of early infant feeding.
AB  - AIM: To report a descriptive study of early infant feeding experiences focusing
      on ACCOUNTS OF WOMEN WHO EXPRESSED MILK EXTENSIVELY IN THE FIRST FEW WEEKS
      POSTPARTUM. BACKGROUND: Relatively little is known about the reasons for
      expressing milk following healthy term births. Evidence indicates it is an
      increasingly common practice during early infant feeding in Westernized
      countries. A more comprehensive understanding of this practice will help midwives
      and nurses assist mothers negotiate early feeding challenges. DESIGN: Qualitative
      data were collected in two phases in the first few weeks postpartum. METHOD:
      Audio-diary and semi-structured interview data from seven British women who
      extensively expressed milk in the first month postpartum were analysed. These
      data were drawn from a larger qualitative longitudinal study which took place in
      2006-2007. Themes, discursive constructions and discourses are identified through
      the use of a feminist informed analysis. FINDINGS: The practice of expressing was
      employed as a solution to managing the competing demands and dilemmas of early
      breastfeeding and ensuring the continued provision of breast milk, thereby
      deflecting potential accusations of poor mothering. In addition, the practice may
      afford a degree of freedom to new mothers. CONCLUSIONS: The need to maintain the
      'good maternal body' can account for the motivation to express milk, although
      there may be reasons to be cautious about promoting expression as a solution to
      breastfeeding difficulties. Education for health professionals, which emphasizes
      the complexities and contradictions of mothering and which challenges
      prescriptive notions of 'good mothering' could better support new mothers in
      their feeding 'choices'.

PMID- 22607058
TI  - Specific changes in total and mitochondrial proteomes are associated with higher
      levels of heterosis in maize hybrids.
AB  - The phenomenon of hybrid vigor (heterosis) has long been harnessed by plant
      breeders to improve world food production. However, the changes that are
      essential for heterotic responses and the mechanisms responsible for heterosis
      remain undefined. Large increases in biomass and yield in high-heterosis hybrids
      suggest that alterations in bioenergetic processes may contribute to heterosis.
      Progeny from crosses between various inbred lines vary in the extent of vigor
      observed. Field-grown maize F1 hybrids that consistently exhibited either low or
      high heterosis across a variety of environments were examined for changes in
      proteins that may be correlated with increased plant vigor and yield.
      Unpollinated ears at the time of flowering (ear shoots) were selected for the
      studies because they are metabolically active, rich in mitochondria, and the
      sizes of the ears are diagnostic of yield heterosis. Total protein and
      mitochondrial proteomes were compared among low- and higher-heterosis hybrids.
      Two-dimensional difference gel electrophoresis was used to identify allelic
      and/or isoform differences linked to heterosis. Identification of differentially
      regulated spots by mass spectrometry revealed proteins involved in stress
      responses as well as primary carbon and protein metabolism. Many of these
      proteins were identified in multiple spots, but analysis of their abundances by
      label-free mass spectrometry suggested that most of the expression differences
      were due to isoform variation rather than overall protein amount. Thus, our
      proteomics studies suggest that expression of specific alleles and/or post
      translational modification of specific proteins correlate with higher levels of
      heterosis.

PMID- 22607059
TI  - Molecular and population analysis of natural selection on the human haptoglobin
      duplication.
AB  - Haptoglobin binds free haemoglobin that prevents oxidative damage produced by
      haemolysis. There is a copy number variant (CNV) in the haptoglobin gene (HP)
      consisting of two alleles, Hp1 (no duplication), and Hp2 (1.7kb duplication
      involving two exons). The spread of the Hp2 allele is believed to have taken
      place under selective pressures conferred by malaria resistance. However,
      molecular evidence is lacking and Hp did not emerge in genomewide SNPs surveys
      for evidence of selection. In Europe, there is geographical constancy of Hp2
      frequency, indicative of absence of clinal pressures and that modern day European
      alleles represent a "snapshot" of their out-of-Africa migrations. In this work we
      test for signatures of natural selection acting on the Hp CNV in a sample from
      the UK population (Avon Longitudinal Study of Parents and Children, ALSPAC). We
      present here heterozygosity decay, pairwise F(ST) values observed between ALSPAC
      and 301 populations from all five populated continents, extended haplotype
      homozygosity analyses involving the CNV and 80 SNPs surrounding the CNV ~500kb in
      each direction, and linkage disequilibrium and pairwise haplotypic analyses
      involving 160 SNPs on chromosome 16q22.1. Taken together, our results represent
      the first molecular analysis of natural selection in the Hp CNV genetic region.

PMID- 22607060
TI  - Influence of dialysis modality and membrane flux on quality of life in
      hemodialysis patients.
AB  - BACKGROUND: The quality of life in patients undergoing hemodialysis is
      significantly disturbed. There are data that hemodiafiltration (HDF) may be more
      effective than conventional hemodialysis in the removal of uremic toxins and may
      reduce frequency and severity of intradialytic and postdialysis adverse symptoms
      in patients. Also, some researchers suggest advantages of using high-flux
      membranes compared with low-flux. OBJECTIVE: The aim of this study was to examine
      whether hemodialysis modality and membrane flux, independent of membrane
      biocompatibility, make differences in quality of life in patients. METHODS: In
      our cross-sectional study, we evaluated 124 patients who were divided, based on
      therapy, into three groups: online HDF, high-flux hemodialysis, and low-flux
      hemodialysis. Data were collected using the Short Form-36 questionnaire combined
      with special questionnaire, which included demographic and clinically related
      questions. RESULTS: Health-related quality of life was better in patients on HDF
      compared with patients on hemodialysis, especially compared with low-flux
      hemodialysis patients in most of the scales and in both dimensions: physical
      component scale and mental component scale. There were no statistically
      significant differences in Short Form-36 domains between high-flux hemodialysis
      and low-flux hemodialysis. CONCLUSION: Our data suggest the potential advantages
      of HDF with regard to influence on quality of life, which is sufficient to
      justify further research in prospective and longitudinal study design.

PMID- 22607062
TI  - Chronic myeloid leukemia in children and adolescents: results of treatment with
      imatinib mesylate.
AB  - Chronic myeloid leukemia (CML) is a rare disease in children, accounting for 2-3%
      of leukemias in this age group. Few studies have reported on efficacy of imatinib
      in childhood CML. The purpose of this retrospective study was to determine the
      efficacy of imatinib in children. A total of 43 patients from age 7 years to 20
      years with newly diagnosed CML received imatinib daily at 260 mg/m(2). Response
      rates, survival and toxicity were evaluated. The median follow-up was 43 months.
      All patients achieved a complete hematological response. Twenty-five (58.1%)
      patients achieved a complete cytogenetic response and 18 (41.9%) achieved a major
      molecular response at any time during their follow-up period. Both overall
      survival and progression-free survival at 43 months' median follow-up were 100%.
      Event-free survival was 92.8%. Imatinib was well tolerated. We conclude that
      imatinib is effective in children and adolescents with CML.

PMID- 22607063
TI  - An evaluation of rheumatology practitioner outreach clinics: a qualitative study.
AB  - BACKGROUND: Services for Rheumatoid Arthritis (RA) have evolved with the
      development of independently led outreach Rheumatology Practitioner (RP) clinics
      in Primary Care (PC). Their clinical and cost effectiveness, compared with
      Secondary Care (SC) services, has not been assessed. The RECIPROCATE study aims
      to evaluate their clinical and cost effectiveness. This part of the study aimed
      to explore health professionals' opinions of rheumatology outreach service.
      METHODS: Using a qualitative design, semi-structured interviews were conducted
      with GPs, practice nurses, hospital doctors and RPs, from one hospital and seven
      PC practices in Norfolk, to elicit their opinions of the service. The interviews
      were analysed using thematic analysis. RESULTS: All participants agreed the
      service was supportive and valuable providing high quality personalised care,
      disease management, social, and educational support. Advantages identified
      included convenience, continuity of care and proximity of services to home. RPs
      helped bridge the communication gap between PC and SC. Some participants
      suggested having a doctor alongside RPs. The service was considered to be cost
      effective for patients but there was uncertainty about cost effectiveness for
      service providers. Few disadvantages were identified the most recurring being the
      lack of other onsite services when needed. It was noted that more services could
      be provided by RPs such as prescribing and joint injections as well as playing a
      more active role in knowledge transfer to PC. CONCLUSIONS: Professionals involved
      in the care of RA patients recognised the valuable role of the RP outreach
      clinics. This service can be further developed in rheumatology and the example
      can be replicated for other chronic conditions.

PMID- 22607065
TI  - Tracking sphingosine metabolism and transport in sphingolipidoses: NPC1
      deficiency as a test case.
AB  - The late endosomal/lysosomal compartment (LE/LY) plays a key role in sphingolipid
      breakdown, with the last degradative step catalyzed by acid ceramidase. The
      released sphingosine can be converted to ceramide in the ER and transported by
      ceramide transfer protein (CERT) to the Golgi for conversion to sphingomyelin.
      The mechanism by which sphingosine exits LE/LY is unknown but Niemann-Pick C1
      protein (NPC1) has been suggested to be involved. Here, we used sphingomyelin,
      ceramide and sphingosine labeled with [(3)H] in carbon-3 of the sphingosine
      backbone and targeted them to LE/LY in low-density lipoprotein (LDL) particles.
      These probes traced LE/LY sphingolipid degradation and recycling as suggested by
      (1) accumulation of [(3)H]-sphingomyelin-derived [(3)H]-ceramide and depletion of
      [(3)H]-sphingosine upon acid ceramidase depletion, and (2) accumulation of [(3)H]
      sphingosine-derived [(3)H]-ceramide and attenuation of [(3)H]-sphingomyelin
      synthesis upon CERT depletion. NPC1 silencing did not result in the accumulation
      of [(3)H]-sphingosine derived from [(3)H]-sphingomyelin/LDL or [(3)H]
      ceramide/LDL. Additional evidence against NPC1 playing a significant role in
      LE/LY sphingosine export was obtained in experiments using the [(3)H]
      sphingolipids or a fluorescent sphingosine derivative in NPC1 knock-out cells.
      Instead, NPC1-deficient cells displayed an increased affinity for sphingosine
      independently of protein-mediated lipid transport. This likely contributes to the
      increased sphingosine content of NPC1 cells.

PMID- 22607066
TI  - Laboratory evaluation of oral treatment of rodents with systemic insecticides for
      control of bloodfeeding sand flies (Diptera: Psychodidae).
AB  - The purpose of this study was to evaluate the efficacy of oral treatment of
      rodents with diets containing the systemic insecticides ivermectin, abamectin,
      imidacloprid, or spinosad, to control bloodfeeding sand flies. We found that
      diets containing concentrations higher than 10 mg/kg abamectin were not palatable
      to rodents, and that a diet containing 10 mg/kg abamectin (a palatable
      concentration) did not cause 100% mortality of bloodfeeding sand flies. Treatment
      of rodents with imidacloprid was effective for less than 3 days post-treatment.
      Treatment of rodents with diets containing 20 mg/kg ivermectin or 5000 mg/kg
      spinosad caused 100% mortality of bloodfeeding sand flies for at least 1 week.
      The efficacy of ivermectin and spinosad also were not reduced when combined with
      the fluorescent tracer dye rhodamine B in a single diet. We also did not observe
      significant benefits by increasing the feeding period of the rodents from 3 to 6
      or 9 days. We conclude that ivermectin and spinosad are effective as rodent
      systemic insecticides against bloodfeeding sand flies, and suggest that weekly
      treatment of wild rodent reservoirs of Leishmania major with bait containing one
      of these systemic insecticides could be a useful tool as part of a sand fly
      control program.

PMID- 22607064
TI  - Reproducibility of BI-RADS breast density measures among community radiologists:
      a prospective cohort study.
AB  - Using data from the Vermont Breast Cancer Surveillance System (VBCSS), we studied
      the reproducibility of Breast Imaging Reporting and Data System (BI-RADS) breast
      density among community radiologists interpreting mammograms in a cohort of
      11,755 postmenopausal women. Radiologists interpreting two or more film-screen
      screening or bilateral diagnostic mammograms for the same woman within a 3- to 24
      month period during 1996-2006 were eligible. We observed moderate-to-substantial
      overall intra-rater agreement for use of BI-RADS breast density in clinical
      practice, with an overall intra-radiologist percent agreement of 77.2% (95%
      confidence interval (CI), 74.5-79.5%), an overall simple kappa of 0.58 (95% CI,
      0.55-0.61), and an overall weighted kappa of 0.70 (95% CI, 0.68-0.73). Agreement
      exhibited by individual radiologists varied widely, with intra-radiologist
      percent agreement ranging from 62.1% to 87.4% and simple kappa ranging from 0.19
      to 0.69 across individual radiologists. Our findings underscore the need for
      additional evaluation of the BI-RADS breast density categorization system in
      clinical practice.

PMID- 22607067
TI  - Bartonella quintana in head lice from Senegal.
AB  - Head and body lice are strict, obligate human ectoparasites with three
      mitochondrial clades (A, B, and C). Body lice have been implicated as vectors of
      human diseases, and as the principal vectors of epidemic typhus, relapsing fever,
      and Bartonella quintata-associated diseases (trench fever, bacillary
      angiomatosis, endocarditis, chronic bacteremia, and chronic lymphadenopathy).
      Using molecular methods (real-time and traditional PCR), we assessed the presence
      of Bartonella quintana DNA in black head lice collected from three locations in
      Senegal. DNA from B. quintana was identified in 19 lice (6.93%) collected from 7
      patients (7%) in Dakar. B. quintana-positive lice collected from three subjects
      were identified as clades C and A.

PMID- 22607068
TI  - Seroprevalence and geographic distribution of Dirofilaria immitis and tick-borne
      infections (Anaplasma phagocytophilum, Borrelia burgdorferi sensu lato, and
      Ehrlichia canis) in dogs from Romania.
AB  - Tick-borne diseases are of great concern worldwide. Despite this, in Romania
      there is only limited information regarding the prevalence of vector-borne
      pathogens in dogs. In all, 1146 serum samples were tested by SNAP((r)) 4Dx((r))
      (IDEXX Laboratories, Inc., Westbrook, ME) for Anaplasma phagocytophilum, Borrelia
      burgdorferi, and Ehrlichia canis antibodies, and for Dirofilaria immitis antigen.
      The correlation between positive cases and their geographic distribution, as well
      as potential risk factors (age, sex, breed, type of dog, habitat, and
      prophylactic treatments) were evaluated. Overall, 129 dogs (11.3%) were
      serologically-positive to one or more of the tested pathogens. The seroprevalence
      for the four infectious agents were: A. phagocytophilum 5.5% (63/1146), D.
      immitis 3.3% (38/1146), E. canis 2.1% (24/1146), and B. burgdorferi 0.5%
      (6/1146). Co-infection with E. canis and A. phagocytophilum was registered in 2
      dogs (0.2%). The geographical distribution of the seropositive cases suggests
      clustered foci in southern regions and in the western part of the country for D.
      immitis, and in the southeastern region (Constanta County) for E. canis. A.
      phagocytophilum and B. burgdorferi showed a homogenous distribution, with a
      tendency for Lyme-positive samples to concentrate in central Romania. For D.
      immitis, A. phagocytophilum, and E. canis, administering prophylactic treatments
      was a risk factor associated with infection. Another associated risk factor was
      the type of dog (stray dogs were at risk being positive for D. immitis, shelter
      dogs for E. canis, and hunting dogs for B. burgdorferi). The prevalence of D.
      immitis was significantly higher in males and in dogs older than 2 years. This
      survey represents the first data detailing A. phagocytophilum and E. canis
      seroprevalence in Romanian dogs, and the most comprehensive epidemiological study
      on vector-borne infections in dogs from this country.

PMID- 22607061
TI  - Cardiovascular redox and ox stress proteomics.
AB  - SIGNIFICANCE: Oxidative post-translational modifications (OPTMs) have been
      demonstrated as contributing to cardiovascular physiology and pathophysiology.
      These modifications have been identified using antibodies as well as advanced
      proteomic methods, and the functional importance of each is beginning to be
      understood using transgenic and gene deletion animal models. Given that OPTMs are
      involved in cardiovascular pathology, the use of these modifications as
      biomarkers and predictors of disease has significant therapeutic potential.
      Adequate understanding of the chemistry of the OPTMs is necessary to determine
      what may occur in vivo and which modifications would best serve as biomarkers.
      RECENT ADVANCES: By using mass spectrometry, advanced labeling techniques, and
      antibody identification, OPTMs have become accessible to a larger proportion of
      the scientific community. Advancements in instrumentation, database search
      algorithms, and processing speed have allowed MS to fully expand on the proteome
      of OPTMs. In addition, the role of enzymatically reversible OPTMs has been
      further clarified in preclinical models. CRITICAL ISSUES: The identification of
      OPTMs suffers from limitations in analytic detection based on the methodology,
      instrumentation, sample complexity, and bioinformatics. Currently, each type of
      OPTM requires a specific strategy for identification, and generalized approaches
      result in an incomplete assessment. FUTURE DIRECTIONS: Novel types of highly
      sensitive MS instrumentation that allow for improved separation and detection of
      modified proteins and peptides have been crucial in the discovery of OPTMs and
      biomarkers. To further advance the identification of relevant OPTMs in advanced
      search algorithms, standardized methods for sample processing and depository of
      MS data will be required.

PMID- 22607070
TI  - Migratory and carnivorous birds in Brazil: reservoirs for Anaplasma and Ehrlichia
      species?
AB  - In order to investigate new hosts for Anaplasmataceae agents in Brazil, we
      collected blood samples from 21 wild birds. Using molecular techniques, we
      detected the presence of Anaplasma phagocytophilum, Ehrlichia chaffeensis, and an
      Ehrlichia species closely related to Ehrlichia canis in carnivorous avian blood
      samples. In addition, an Ehrlichia species closely related to an Ehrlichia
      species found in wild felines in Brazil was also detected in a goose blood
      sample. Wild birds may play a role as carriers of Anaplasmataceae agents in
      Brazil.

PMID- 22607069
TI  - Trends in national surveillance data for bat rabies in the United States: 2001
      2009.
AB  - Rabies remains an important public health concern in the United States, with most
      human cases associated with bat rabies virus variants. Cases of rabies virus (RV)
      infection in bats are widely distributed across the continental United States and
      elsewhere in the Americas. In this retrospective study, data on bats submitted to
      state laboratories for RV diagnosis between 2001 and 2009 were analyzed to
      investigate epidemiological trends in the United States. Season, region, and
      roosting habits were the primary risk factors of interest. During the study
      interval, more than 205,439 bats were submitted for RV diagnosis, and 6.7% of
      these bats were rabid. Increased odds of a submitted bat being rabid were
      associated with species that exhibit inconspicuous roosting habits, bats
      originating in the Southwest, and bats submitted for diagnosis during the fall.
      Periodic analysis of zoonotic disease surveillance is recommended to detect
      changes in trends regarding geographic distribution, seasonal fluctuations, and
      host associations; this is particularly necessary, as existing trends may be
      influenced by climate change or other emerging factors.

PMID- 22607071
TI  - National and regional associations between human West Nile virus incidence and
      demographic, landscape, and land use conditions in the coterminous United States.
AB  - The incidence of human West Nile virus (WNV) varies spatially and temporally and
      is influenced by a wide range of biotic and abiotic factors. There are numerous
      important vector species, with variable geographic ranges and ecologies,
      considered crucial to the transmission of WNV in the coterminous United States.
      To date there has been a lack of a systematic investigation in the United States,
      at a regional scale, of the wide variety of landscape, land use, and demographic
      influences on WNV incidence. In this study, we use published vector species
      distribution maps, as well as prominent landscape features, to define six
      distinct regions of the coterminous United States. We relate data on demographic,
      landscape, and land use conditions to the incidence of human WNV by region
      recorded at county level in the coterminous United States from 2002-2009. The
      observed relationships varied by region with the Great Plains, Northwest, and
      Southwest regions showing high WNV incidence associated with rural irrigated
      landscapes, indicating the importance of Culex tarsalis as the primary vector. In
      the Southeast, the percent of the population in poverty was positively associated
      with high WNV incidence, potentially indicating the quality of housing in
      relation to the vector Culex quinquefasciatus, a mosquito that often feeds
      indoors. The Northeast region human WNV incidence was positively associated with
      agricultural landscapes, potentially implying the importance of Culex restuans in
      a region generally thought of as being dominated by Culex pipiens transmission.
      There was strong spatial autocorrelation in most of the regions, but with a
      spatial autologistic term accounted for in binary logistic regression models,
      there were significant landscape, land use, and demographic covariates for each
      region.

PMID- 22607072
TI  - Ticking all the boxes? A systematic review of education and communication
      interventions to prevent tick-borne disease.
AB  - Tick-borne disease has become increasingly prevalent across Europe. Despite the
      effectiveness of protective behaviors, relatively few people adopt them when in
      areas where ticks are known to be present. In this systematic review we
      identified studies that assessed the impact of any educational or behavioral
      interventions intended to encourage the widespread use of protective behaviors
      against tick-borne disease. An extensive search of electronic databases returned
      a total of only nine such studies. Only two of these were fully randomized
      controlled trials, with the remaining studies using weaker designs and often
      relying solely on self-reports to assess behavior. The majority of research in
      this area has not explicitly noted the consideration of any formal psychological
      theory on how best to promote behaviors that protect health. Nonetheless, the
      results show that both knowledge of and attitudes towards tick-borne disease are
      amenable to change, although the stability of these changes over time has not yet
      been determined. Not all intervention strategies have proved effective, with some
      producing detrimental effects. More theory-based, methodologically-robust studies
      are urgently required if we are to gain a better understanding of the most
      effective strategies for encouraging members of the public to adopt behaviors
      known to protect against tick-borne disease.

PMID- 22607073
TI  - Serum immunoglobulin G avidity test as a tool for improving diagnosis of cat
      scratch disease.
AB  - Cat scratch disease (CSD) is a common cause of subacute infectious regional
      lymphadenitis, caused by Bartonella henselae. Presently, detection of anti-B.
      henselae antibodies by immunofluorescence antibody assay or enzyme immunoassay
      (EIA) is the most widely used diagnostic test for CSD, but both are limited in
      establishing the timing of infection with B. henselae. In the present work we
      developed an avidity test for anti-B. henselae immunoglobulin G (IgG) based on
      EIA to distinguish recent from past CSD. We used 101 serum samples from 79 CSD
      patients with positive anti-B. henselae IgG as verified by EIA, and
      systematically developed an avidity assay using various detergent (urea)
      concentrations and incubation settings to optimize the test conditions to
      differentiate early CSD (less than 12 weeks) from late CSD (12 weeks or more).
      After serial experiments, the optimal conditions for performing the avidity test
      included incubation for 10 min at room temperature with 8 M urea at pH 7.4, and
      these parameters were used in the study. Our experiments showed that while the
      avidity indexes (AIs) of the early CSD samples were widely distributed, all the
      late CSD sera samples had AIs above 43, indicating that an AI <43 can serve as
      evidence of early CSD. The results of this study indicate that the avidity test
      can be useful in the serodiagnosis of CSD, particularly when anti-B. henselae IgM
      antibodies are not detected.

PMID- 22607074
TI  - Seasonality of Ixodes ricinus ticks on vegetation and on rodents and Borrelia
      burgdorferi sensu lato genospecies diversity in two Lyme borreliosis-endemic
      areas in Switzerland.
AB  - We compared Ixodes ricinus questing density, the infestation of rodents by
      immature stages, and the diversity of Borrelia burgdorferi sensu lato (sl) in
      questing ticks and ticks collected from rodents in two Lyme borreliosis (LB)
      endemic areas in Switzerland (Portes-Rouges [PR] and Staatswald [SW]) from 2003
      to 2005. There were variations in the seasonal pattern of questing tick densities
      among years. Questing nymphs were globally more abundant at PR than at SW, but
      the proportion of rodents infested by immature ticks was similar (59.4% and 61%,
      respectively). Questing tick activity lasted from February to November with a
      strong decline in June. The seasonal pattern of ticks infesting rodents was
      different. Ticks infested rodents without decline in summer, suggesting that the
      risk of being bitten by ticks remains high during the summer. Rodents from SW
      showed the highest infestation levels (10+/-21.6 for larvae and 0.54+/-1.65 for
      nymphs). The proportion of rodents infested simultaneously by larvae and nymphs
      (co-feeding ticks) was higher at SW (28%) than at PR (11%). Apodemus flavicollis
      was the species the most frequently infested by co-feeding ticks, and Myodes
      glareolus was the most infective rodent species as measured by xenodiagnosis. At
      PR, the prevalence of B. burgdorferi sl in questing ticks was higher (17.8% for
      nymphs and 32.4% for adults) than at SW (10.4% for nymphs and 24.8% for adults),
      with B. afzelii as the dominant species, but B. garinii, B. burgdorferi sensu
      stricto, and B. valaisiana were also detected. Rodents transmitted only B.
      afzelii (at PR and at SW) and B. bavariensis (at SW) to ticks, and no mixed
      infection by additional genospecies was observed in co-feeding ticks. This
      implies that co-feeding transmission does not contribute to genospecies
      diversity. However, persistent infections in rodents and co-feeding transmission
      contribute to the perpetuation of B. afzelii in nature.

PMID- 22607075
TI  - Cross-sectional survey of the seroprevalence of Puumala hantavirus in Austria.
AB  - The prevalence of Puumala hantavirus infections in Austria and the occupational
      exposure of military personnel to this virus were assessed in 2009 in an
      exploratory nationwide cross-sectional seroprevalence survey in 526 healthy
      individuals, of which 222 were soldiers and 304 were civilians. In addition,
      information on possible risk factors for hantavirus exposure, including previous
      foreign military assignments, residential area, occupational animal contact, and
      regular outdoor activities, was obtained. Immunoglobulin G antibodies against
      Puumala hantavirus were examined with a commercial enzyme-linked immunosorbent
      assay. Overall, 7 (1.3%) individuals, aged 19, 22, 24, 24, 26, 38, and 60 years,
      tested positive on serologic screening. There were no significant differences
      between the seroprevalence of the virus and any of the variables surveyed. Our
      data demonstrate serologic evidence of Puumala hantavirus infection among the
      Austrian population, with a stable prevalence in the past decade. When compared
      with the general population, no increased risk of exposure to Puumala hantavirus
      could be detected for military personnel.

PMID- 22607076
TI  - Impacts of an introduced forest pathogen on the risk of Lyme disease in
      California.
AB  - Global changes such as deforestation, climate change, and invasive species have
      the potential to greatly alter zoonotic disease systems through impacts on
      biodiversity. This study examined the impact of the invasive pathogen that causes
      sudden oak death (SOD) on the ecology of Lyme disease in California. The Lyme
      disease bacterium, Borrelia burgdorferi, is maintained in the far western United
      States by a suite of animal reservoirs including the dusky-footed woodrat
      (Neotoma fuscipes) and deer mouse (Peromyscus maniculatus), and is transmitted by
      the western black-legged tick (Ixodes pacificus). Other vertebrates, such as the
      western fence lizard (Sceloporus occidentalis), are important tick hosts but are
      not reservoirs of the pathogen. Previous work found that higher levels of SOD are
      correlated with greater abundance of P. maniculatus and S. occidentalis and lower
      N. fuscipes abundance. Here we model the contribution of these tick hosts to Lyme
      disease risk and also evaluate the potential impact of SOD on infection
      prevalence of the tick vector. By empirically parameterizing a static model with
      field and laboratory data on tick hosts, we predict that SOD reduces an important
      index of disease risk, nymphal infection prevalence, leading to a reduction in
      Lyme disease risk in certain coastal woodlands. Direct observational analysis of
      the impact of SOD on nymphal infection prevalence supports these model results.
      This study underscores the important direct and indirect impacts of invasive
      plant pathogens on biodiversity, the transmission cycles of zoonotic diseases,
      and ultimately human health.

PMID- 22607078
TI  - Case management and supportive treatment for patients with Crimean-Congo
      hemorrhagic fever.
AB  - Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne infection which has been
      increasing in Turkey and European countries since the year 2000. The disease is
      particularly endemic in the Middle East and in some African countries. It is also
      seen in European countries as a travel infection. Patients with confirmed
      diagnosis are usually hospitalized for monitoring, while patients with good
      overall condition may be monitored on an outpatient basis. Hospitals that manage
      CCHF should have easy access to a blood bank, and tertiary care hospitals must
      have a well-equipped intensive care unit. Strict blood and body fluid control
      precautions should be started on admission to limit CCHF exposure. The follow-up
      period for each patient is determined based on individual clinical status and
      laboratory values. Since there is no specific antiviral treatment for CCHF,
      supportive treatment is essential. This review highlights some of the major
      features of case monitoring and supportive treatment in CCHF.

PMID- 22607077
TI  - Hantaan virus surveillance in small mammals at firing points 10 and 60,
      Yeoncheon, Gyeonggi Province, Republic of Korea.
AB  - We used epidemiological data and indirect fluorescent antibody tests to determine
      the Hantaan virus (HTNV) antibody-positive (Ab+) prevalence in small mammals
      captured at firing point 10 (FP-10) and firing point 60 (FP-60), Gyeonggi
      Province, near the demilitarized zone, Republic of Korea (ROK), from 2001 to
      2005. We used these data, combined with the partial M segment amplified from HTNV
      recovered from lung tissues of Apodemus agrarius, to clarify the genetic
      diversity and phylogenetic relationships among HTNV strains in the ROK. Of the
      eight species of rodents and one insectivore species captured, A. agrarius
      accounted for 93.4% and 88.5% at FP-10 and FP-60, respectively. Only two species
      of rodents, A. agrarius and Micromys minutus, were HTNV Ab+. The overall HTNV Ab+
      prevalence for A. agrarius captured at FP-10 and FP-60 was 23.3% (121/520) and
      14.5% (94/647), respectively. The hantaviral reverse transcription-polymerase
      chain reaction-positive rate of Ab+ A. agrarius was 74.2% (167/215), and the
      phylogenetic trees, based on the 269-nucleotide G2-encoding M segment,
      demonstrated that HTNV strains from FP-10 and FP-60 were distantly segregated
      from HTNV of other geographic regions in Korea and China. These data are useful
      in the development of risk reduction strategies for the prevention of hantavirus
      infections among military personnel, especially during training or the event of
      hostilities, and civilian populations.

PMID- 22607079
TI  - First record of autochthonous canine leishmaniasis in Hungary.
AB  - Hungary is traditionally regarded as a leishmaniasis-free country, and human or
      canine cases diagnosed locally have been recorded as imported. However, recent
      entomological surveys have verified the presence in Hungary of Phlebotomus
      neglectus and Phlebotomus perfiliewi perfiliewi, which have been incriminated as
      competent vectors of Leishmania infantum elsewhere in Europe. Following the
      occurrence in October 2007 of an undisputable clinical case of L. infantum canine
      leishmaniasis (CanL) in a 4-year-old female pug in a kennel of 20 dogs in Tolna
      province, an investigation was performed to assess the infection status in that
      canine population and to search for putative phlebotomine vectors. Another female
      pug became sick during the study period (May-November 2008) and L. infantum was
      confirmed as the causative agent. The other animals appeared clinically healthy;
      however, 4 additional dogs were found positive by indirect fluorescent antibody
      test (2 dogs), or by buffy-coat PCR (1 dog), or by both methods (1 dog). Hence
      the overall Leishmania infection prevalence in the kennel was 30% (6/20). All
      dogs were born in the same place and had been always kept outdoors. They had
      neither been abroad nor received a blood transfusion. No sand flies were
      collected with CDC Standard Miniature Light traps, Mosquito Magnet((r)) X (MMX)
      dry ice-baited traps, or sticky traps placed either in or around the kennel and
      at nearby chicken yards during July and August of 2008 and 2009. Considering the
      dogs' historical background and the failure to trap any sand fly vectors in the
      kennel area, the origin of CanL in this site remains unexplained.

PMID- 22607080
TI  - High seroprevalence of Coxiella burnetii antibodies in veterinarians associated
      with cattle obstetrics, Bavaria, 2009.
AB  - Q fever is a zoonosis caused by Coxiella burnetii. Infection can result in severe
      disease. However, little is known about the risk of infection in veterinarians.
      In a cross-sectional study among German veterinarians, participants provided sera
      and completed an exposure questionnaire. We investigated predictors for
      seropositivity using multivariable logistic regression modelling. The 424
      participants' median age was 40 (18-74) years, and 276 (65%) were female. Sera of
      162 (38%) were positive for Coxiella burnetii phase II IgG antibodies (by ELISA
      and IFAT). Predictors for seropositivity were occupational exposure to cattle
      (aOR 2.83, 95% CI 1.64-4.87), occupational exposure to sheep (2.09, 1.22-3.58),
      male sex (1.9, 1.15-3.13), and increasing age (30-39 years: 4.91, 2.00-12.04; 40
      49 years: 5.32, 2.12-13.33; >50 years: 6.70, 2.60-17.25; compared with <30
      years). When investigating occupational exposure to cattle and sheep in detail in
      a separate model, the seroprevalence increased with increasing numbers of cattle
      obstetrics procedures performed per month, and with increasing numbers of
      individual cattle treated per week. The high antibody prevalence implies a high
      lifetime-risk of Q fever in veterinarians. Cattle veterinarians, especially those
      frequently performing obstetrics, should be counseled early in their career on
      the clinical picture of Q fever, and on specific risks.

PMID- 22607081
TI  - Salmonella isolates from wild-caught Tokay geckos (Gekko gecko) imported to the
      U.S. from Indonesia.
AB  - Reptiles account for ~10% of live animal shipments imported to the United States
      (U.S.), the majority of which are sold in the pet trade. Characterizing
      Salmonella shedding by imported reptiles is of value to public health, the pet
      industry, and veterinary medicine. Here we report results of a pilot survey of
      Salmonella serotypes isolated from wild-caught Indonesian Tokay geckos (Gekko
      gecko) imported to the U.S. Upon arrival, the geckos were individually housed
      until a fecal sample was acquired for Salmonella culture. The geckos were divided
      into three groups with variable numbers to investigate density effects. A second
      group was imported after 3 months and combined with the previous groups. A total
      of 88 Salmonella isolates were obtained from 110 geckos surveyed, representing 14
      serogroups and 17 unique serotypes. Group prevalence ranged from 31-73%. A
      significant increase in prevalence and a change in serotype richness were
      detected between the time of import and 6 months later at necropsy. Six isolates
      (6.8%) expressed resistance to more than one antibiotic. All S. enterica subsp.
      enterica Adelaide isolates were resistant to nalidixic acid and sulfisoxazole,
      one S. enterica subsp. arizonae 61:k:z35 isolate was resistant to ampicillin and
      sulfisoxazole, and another 61:k:z35 isolate was resistant to streptomycin and
      sulfisoxazole. Forty-three additional isolates expressed resistance only to
      sulfisoxazole. The mechanisms for increased prevalence and apparent change in
      serotype richness are unknown, but could be due to stress associated with trade,
      transport, and captivity, increased transmission from unnaturally high densities,
      or contact with other species shedding Salmonella along the trade route. Future
      studies to differentiate the physical, social, and physiological effects of trade
      related conditions on Salmonella shedding and transmission among reptiles will
      benefit the industry by identifying ways to reduce mortality, and safeguard the
      individuals handling animals along the transport chain and other species
      encountered en route.

PMID- 22607082
TI  - Lung hernia following robotic-assisted mitral valve repair.
AB  - Lung hernia is an uncommon diagnosis characterized by lung tissue protruding
      through a chest wall defect. It may occur spontaneously, as a congenital defect,
      as a result of trauma, or as a postsurgical complication. We describe the
      occurrence of lung hernia and subsequent successful herniorraphy in two patients
      following robotic-assisted mitral valve repair.

PMID- 22607083
TI  - Pharmaceutical design of a new lactose-free coprocessed excipient: application of
      hydrochlorothiazide as a low solubility drug model.
AB  - Most co-processed excipients used in direct-compression tablets contain lactose,
      which prevents lactose-intolerant patients from taking such tablets. Therefore, a
      novel lactose-free co-processed excipient for direct compression tablets has been
      prepared. Microcrystalline cellulose and dicalcium phosphate dehydrate were used
      as primary excipients which underwent a wet granulation process and factorial
      experiment in order to ascertain the best prototype. Finally, the best two
      prototypes were added to hydrochlorothiazide, which has chosen as the model drug
      because of its low solubility. An extensive characterization of the new excipient
      as well as the drug loaded tablets is reported. Our results show adequate
      parameters (rheological and compression behavior, uniformity of weight,
      disintegration, friability, crushing force and cohesion index). Moreover, the
      biopharmaceutical profile was evaluated; the tablets exhibits a Weibull kinetic
      function and fast drug release.

PMID- 22607084
TI  - Comparison of acid generation in EUV lithography films of poly(4-hydroxystyrene)
      (PHS) and noria adamantyl ester (Noria-AD(50)).
AB  - The mechanism for acid production in phenolic extreme ultraviolet (EUV)
      lithography films containing triphenylsulfonium triflate (Ph(3)S(+)TfO(-)) acid
      generator has been investigated by electron paramagnetic resonance (EPR)
      spectroscopy and by use of the acid indicator coumarin 6 (C6). Gamma radiolysis
      was substituted for the EUV radiation with the assumption that the chemistry
      generated by ionization of the matrix does not depend on the ionization source.
      Poly(4-hydroxystyrene) (PHS) was first investigated as a well-studied standard,
      after which the water-wheel-like cyclic oligomer derivative containing pendant
      adamantyl ester groups, noria-AD(50), was investigated. EPR measurements confirm
      that the dominant free radical product is a phenoxyl derivative (PHS-O(*) or
      noria-O(*)) that exhibits quite slow stretched exponential recombination kinetics
      at room temperature. Also observed at 77 K was the presence of a significant
      hydrogen atom product of radiolysis. The G value or yield of acid production in
      thin lithography films was measured with the C6 indicator on a fused silica
      substrate. It was found that a significant amount of acid is generated via energy
      transfer from the irradiated fused-silica substrate to the Ph(3)S(+)TfO(-) in the
      films. By varying the film thickness on the substrates, the substrate effect on
      the acid yield was quantitatively determined. After subtraction of the
      contribution from the substrates, the acid yield G value in the PHS film with 10
      wt % Ph(3)S(+)TfO(-) and 5 wt % C6 was determined to be 2.5 +/- 0.3 protons per
      100 eV of radiation. The acid yield of noria-AD(50) films was found to be 3.2 +/-
      0.3 protons per 100 eV.

PMID- 22607085
TI  - A systematic review of the impact of stigma and nihilism on lung cancer outcomes.
AB  - BACKGROUND: This study systematically reviewed the evidence on the influence of
      stigma and nihilism on lung cancer patterns of care; patients' psychosocial and
      quality of life (QOL) outcomes; and how this may link to public health programs.
      METHODS: Medline, EMBASE, ProQuest, CINAHL, PsycINFO databases were searched.
      Inclusion criteria were: included lung cancer patients and/or partners or
      caregivers and/or health professionals (either at least 80% of participants had
      lung cancer or were partners or caregivers of lung cancer patients, or there was
      a lung cancer specific sub-group focus or analysis), assessed stigma or nihilism
      with respect to lung cancer and published in English between 1st January 1999 and
      31st January 2011. Trial quality and levels of evidence were assessed. RESULTS:
      Eighteen articles describing 15 studies met inclusion criteria. The seven
      qualitative studies were high quality with regard to data collection, analysis
      and reporting; however most lacked a clear theoretical framework; did not address
      interviewer bias; or provide a rationale for sample size. The eight quantitative
      studies were generally of low quality with highly selected samples, non
      comparable groups and low participation rates and employed divergent theoretical
      and measurement approaches. Stigma about lung cancer was reported by patients and
      health professionals and was related to poorer QOL and higher psychological
      distress in patients. Clear empirical explorations of nihilism were not evident.
      There is qualitative evidence that from the patients' perspectives public health
      programs contribute to stigma about lung cancer and this was supported by
      published commentary. CONCLUSIONS: Health-related stigma presents as a part of
      the lung cancer experience however there are clear limitations in the research to
      date. Future longitudinal and multi-level research is needed and this should be
      more clearly linked to relevant theory.

PMID- 22607087
TI  - One-pot asymmetric synthesis of 2- and 2,3-disubstituted tetrahydrofuran
      derivatives.
AB  - A novel and convenient one-pot asymmetric synthesis of 2- and 2,3-disubstituted
      tetrahydrofurans has been achieved in 56-81% yields and 86-99% ee from aliphatic
      and aromatic aldehydes via an allyl/crotyl/alkoxyallylboration-hydroboration
      iodination-cyclization reaction sequence.

PMID- 22607086
TI  - Comparative genome analysis of central nitrogen metabolism and its control by
      GlnR in the class Bacilli.
AB  - BACKGROUND: The assimilation of nitrogen in bacteria is achieved through only a
      few metabolic conversions between alpha-ketoglutarate, glutamate and glutamine.
      The enzymes that catalyze these conversions are glutamine synthetase,
      glutaminase, glutamate dehydrogenase and glutamine alpha-ketoglutarate
      aminotransferase. In low-GC Gram-positive bacteria the transcriptional control
      over the levels of the related enzymes is mediated by four regulators: GlnR,
      TnrA, GltC and CodY. We have analyzed the genomes of all species belonging to the
      taxonomic families Bacillaceae, Listeriaceae, Staphylococcaceae,
      Lactobacillaceae, Leuconostocaceae and Streptococcaceae to determine the
      diversity in central nitrogen metabolism and reconstructed the regulation by
      GlnR. RESULTS: Although we observed a substantial difference in the extent of
      central nitrogen metabolism in the various species, the basic GlnR regulon was
      remarkably constant and appeared not affected by the presence or absence of the
      other three main regulators. We found a conserved regulatory association of GlnR
      with glutamine synthetase (glnRA operon), and the transport of ammonium (amtB
      glnK) and glutamine/glutamate (i.e. via glnQHMP, glnPHQ, gltT, alsT). In addition
      less-conserved associations were found with, for instance, glutamate
      dehydrogenase in Streptococcaceae, purine catabolism and the reduction of nitrite
      in Bacillaceae, and aspartate/asparagine deamination in Lactobacillaceae.
      CONCLUSIONS: Our analyses imply GlnR-mediated regulation in constraining the
      import of ammonia/amino-containing compounds and the production of intracellular
      ammonia under conditions of high nitrogen availability. Such a role fits with the
      intrinsic need for tight control of ammonia levels to limit futile cycling.

PMID- 22607088
TI  - Serum 25-hydroxyvitamin D3 and body composition in an elderly cohort from
      Germany: a cross-sectional study.
AB  - BACKGROUND: Emerging evidence indicates that there is an association between
      vitamin D and obesity. The aim of this study was to investigate whether the level
      of serum 25-hydroxyvitamin D3 [25(OH)D3] in the elderly is influenced by
      parameters of anthropometry and body composition independent of potential
      confounding lifestyle factors and the level of serum intact parathyroid hormone
      (iPTH). METHODS: Cross-sectional data of 131 independently living participants
      (90 women, 41 men; aged 66-96 years) of the longitudinal study on nutrition and
      health status in senior citizens of Giessen, Germany were analysed.
      Concentrations of 25(OH)D3 and iPTH were ascertained by an
      electrochemiluminescence immunoassay. Body composition was measured by a
      bioelectrical impedance analysis. We performed univariate and multiple regression
      analyses to examine the influence of body composition on 25(OH)D3 with
      adjustments for age, iPTH and lifestyle factors. RESULTS: In univariate
      regression analyses, 25(OH)D3 was associated with body mass index (BMI), hip
      circumference and total body fat (TBF) in women, but not in men. Using multiple
      regression analyses, TBF was shown to be a negative predictor of 25(OH)D3 levels
      in women even after controlling for age, lifestyle and iPTH (beta = -0.247; P =
      0.016), whereas the associations between BMI, hip circumference and 25(OH)D3 lost
      statistical significance after adjusting for iPTH. In men, 25(OH)D3 was not
      affected by anthropometric or body composition variables. CONCLUSIONS: The
      results indicate that 25(OH)D3 levels are affected by TBF, especially in elderly
      women, independent of lifestyle factors and iPTH.

PMID- 22607089
TI  - Identification and quantification of phenobarbital in a mummified body 10 years
      after death.
AB  - This article reports the determination of phenobarbital in the mummified body of
      a 56-year-old man found completely mummified 10 years after his death. When
      alive, he was being treated for epilepsy with phenobarbital, and the recent
      analyses, performed with both immunochemical techniques and gas chromatography
      with mass spectrometry (GC-MS), have revealed the presence of this substance in
      various tissues: the mean content of barbiturate in the mummified liver tissue
      was 93 MUg/g, 216 MUg/g in the heart, 17 MUg/g in the lungs, 12 MUg/g in muscles,
      and 31 MUg/g in the skin. Preliminary screening tests with immunochemical
      techniques to evaluate the presence of other drugs were also performed. The
      sample resulted negative for all substances tested. Phenobarbital can be
      identified and quantified thanks to its excellent chemical stability and a
      hypothesis of what the concentrations in the fresh tissue could have been has
      also been reported.

PMID- 22607090
TI  - Cross-sectional study of adherence to venous thromboembolism prophylaxis
      guidelines in hospitalized patients. The Trombo-Brit study.
AB  - BACKGROUND: DVT is the main cause of death in hospitalized patients and
      thromboprophylaxis is the only way to prevent these deaths. International
      recommendations suggested that active monitoring of DVT/PE prophylaxis can
      improve the efficacy in Hospitals. METHODS: We performed a cohort study in three
      consecutives periods to evaluate DVT prophylaxis in 388 adults hospitalized in a
      General Hospital. RESULTS: 85% of the population had high risk factors for DVT.
      Thromboprophylaxis was in accordance with local and International guidelines
      (ACCP 2008) in 72.7% and 86% of the patients respectively. No significant
      difference could be founded between clinical and surgical patients. One every 10
      patients received higher prophylaxis than suggested by guidelines and two out of
      ten received deficient or no prophylaxis. The worst 2 groups of patients were
      those with moderate/low risk of DVT and the group with a contraindication to
      pharmacologic prophylaxis. We observed a progressive improvement of the DVT
      prophylaxis in the 3 periods of evaluation. CONCLUSIONS: Although the rate of
      recommended thromboprophylaxis is higher than many other reports in the region we
      still have some areas where we need to improve. Regular audits like these are
      very helpful to find out what specific areas of the hospital needs some careful
      attention in order to have a better quality of assistance.

PMID- 22607091
TI  - New antifouling silica hydrogel.
AB  - In this work, a new antifouling silica hydrogel was developed for potential
      biomedical applications. A zwitterionic polymer, poly(carboxybetaine
      methacrylate) (pCBMA), was produced via atom-transfer radical polymerization and
      was appended to the hydrogel network in a two-step acid-base-catalyzed sol-gel
      process. The pCBMA silica aerogels were obtained by drying the hydrogels under
      supercritical conditions using CO(2). To understand the effect of pCBMA on the
      gel structure, pCBMA silica aerogels with different pCBMA contents were
      characterized using scanning electron microscopy (SEM), nuclear magnetic
      resonance (NMR) spectroscopy, and the surface area from Brauner-Emmet-Teller
      (BET) measurements. The antifouling property of pCBMA silica hydrogel to resist
      protein (fibrinogen) adsorption was measured using enzyme-linked immunosorbent
      assay (ELISA). SEM images revealed that the particle size and porosity of the
      silica network decreased at low pCBMA content and increased at above 33 wt % of
      the polymer. The presence of pCBMA increased the surface area of the material by
      91% at a polymer content of 25 wt %. NMR results confirmed that pCBMA was
      incorporated completely into the silica structure at a polymer content below 20
      wt %. A protein adsorption test revealed a reduction in fibrinogen adsorption by
      83% at 25 wt % pCBMA content in the hydrogel compared to the fibrinogen
      adsorption in the unmodified silica hydrogel.

PMID- 22607092
TI  - P53-mediated GSH depletion enhanced the cytotoxicity of NO in silibinin-treated
      human cervical carcinoma HeLa cells.
AB  - Silibinin is an active constituent extracted from the blessed milk thistle
      (Silybum marianum). In a previous study, we demonstrated that silibinin treatment
      induced the generation of reactive nitrogen species (RNS), which were associated
      with reactive oxygen species (ROS), and caused apoptosis and autophagy in HeLa
      cells. Another study reported that silibinin treatment attenuated the apoptotic
      effect of sodium nitroprusside (SNP) by generating ROS in rat pheochromocytoma
      PC12 cells [ 1 ]. To clarify the relationship between RNS and nitric oxide (NO)
      in HeLa cells, we chose SNP as a NO donor to inhibit the cell viability. We found
      that silibinin treatment did not reduce the cytotoxicity of NO by reducing the
      ROS-induced RNS levels; conversely, silibinin treatment enhanced the cytotoxicity
      of NO. Pre-treatment with the NO scavenger PTIO preserved the viability of SNP-
      or silibinin-treated cells. Buthionine sulfoximine (BSO) treatment was also used
      to deplete the level of glutathione (GSH) and subsequently enhance the
      cytotoxicity of NO. Pre-treatment with BSO enhanced the SNP-induced reduction of
      cell viability but had no such effects in the silibinin-treated cells. These
      results led us to investigate whether silibinin treatment could induce the
      depletion of GSH. JNK and p53 have been shown to mediate the depletion of GSH [ 2
      , 3 ], and we previously demonstrated the existence of a ROS-JNK-p53 cycle in
      silibinin-treated HeLa cells [ 4 ]. Thus, we speculated that p53 also plays a
      crucial role in the silibinin-induced GSH depletion. To elucidate the role of p53
      in this process, A431 cells were used because they are naturally devoid of a
      functional p53 (p53His273 mutation). To our surprise, silibinin treatment did not
      lower the GSH level in A431 cells but rather elevated the GSH level. Unlike the
      ROS level, the NO level was still up-regulated by silibinin treatment in A431
      cells. Cumulatively, these findings support the idea that the silibinin-induced
      GSH depletion, which is mediated by p53, enhances the cytotoxicity of NO in HeLa
      cells.

PMID- 22607094
TI  - Development and psychometric testing of a new tool for detecting moral distress:
      the Moral Distress Thermometer.
AB  - AIM: To report the development and psychometric testing of the Moral Distress
      Thermometer. The Moral Distress Thermometer is a new screening tool to measure
      moral distress in nurses who practise in the hospital setting. BACKGROUND: Moral
      distress occurs when one knows the ethically correct thing to do, but is
      prevented from acting on that perceived obligation. It is a well documented
      phenomenon with negative consequences that may be experienced by nurses. Creating
      an instrument to effectively and efficiently measure moral distress in a timely
      way has been identified as a priority for nursing. DESIGN: This study used a
      cross-sectional survey design. METHODS: Data collection for this research
      occurred in 2009. Participants simultaneously completed either the adult or
      pediatric version of the Moral Distress Scale version 2009 and the Moral Distress
      Thermometer. A total of 529 participants from various clinical areas completed
      both tools. RESULTS: Coefficients alpha were adequate for both Adult (0.90) and
      Pediatric (0.92) Moral Distress Scale 2009 scales. Statistically significant
      Pearson correlations were found for the Moral Distress Thermometer with Adult
      Moral Distress Scale 2009 and Pediatric Moral Distress Scale 2009 and higher
      Moral Distress Thermometer, Adult Moral Distress Scale 2009 and Pediatric Moral
      Distress Scale 2009 means for participants who had left or who considered leaving
      a position because of moral distress. CONCLUSION: These findings provide support
      for the validity of the Moral Distress Thermometer.

PMID- 22607093
TI  - Type 2 Porcine Reproductive and Respiratory Syndrome Virus infection mediated
      apoptosis in B- and T-cell areas in lymphoid organs of experimentally infected
      pigs.
AB  - Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infection is
      characterized by persisting in lungs and lymphoid tissue, resulting in systemic
      lymphoid depletion. The aim of this study was to correlate the histological
      changes, viral antigen expression and apoptosis phenomena in tonsil, medial
      retropharyngeal and mediastinal lymph nodes of 12 pigs inoculated with a type 2
      PRRSV isolate (Chilean strain 2402). Apoptosis phenomena were observed mainly in
      lymphocytes and secondly in macrophages of lymph nodes and tonsils of inoculated
      animals, showing a peak of both apoptotic cells and viral antigen expression at
      the end of the study (21 dpi). However, the number of apoptotic cells was higher
      than the number of PRRSV-positive cells at the end of the study. This finding
      together with the location of apoptotic cells and PRRSV-positive cells in
      different structures of lymphoid organs supports the hypothesis that PRRSV
      positive macrophages might modulate the apoptosis phenomena in other cells,
      mainly lymphocytes, by means of an indirect mechanism. Furthermore, apoptotic
      cells were detected both in B- and T-cell areas of lymphoid organs, suggesting
      that apoptosis phenomena may play a role in the impairment of the host immune
      response during PRRS.

PMID- 22607095
TI  - Neutrophil superoxide production in the presence of cigarette smoke extract,
      nicotine and cotinine.
AB  - AIM: To determine the effect of cigarette smoke extract, nicotine and cotinine on
      lucigenin-detectable neutrophil superoxide production. MATERIALS & METHODS:
      Neutrophils from periodontally healthy individuals were treated with aqueous
      smoke extract, nicotine and cotinine, prior to stimulation or at the same time as
      stimulation with Fusobacterium nucleatum, IgG-opsonized Staphylococcus aureus and
      Escherichia coli Lipopolysaccharide (LPS). Superoxide generation was determined
      by lucigenin chemiluminescence. RESULTS: Smoke extract induced superoxide release
      from neutrophils (p <0.0001) in a dose-dependent manner. By contrast, superoxide
      generation by neutrophils in response to pathologically relevant stimuli was
      inhibited by pre-treatment with smoke extract (p <0.01). This inhibition did not
      require the continued presence of the extract. A similar reduction in stimulated
      superoxide production by smoke extract was detected when neutrophils were
      simultaneously exposed to the extract and stimuli. Nicotine and cotinine (0-10
      MUg/ml) had no effect on superoxide release from unstimulated or stimulated
      neutrophils. CONCLUSIONS: Stable water-soluble components of cigarette smoke
      directly induce superoxide generation by otherwise unstimulated neutrophils, but
      reduce superoxide responses of cells to pathologically relevant stimuli. These
      data suggest potential neutrophil-mediated mechanisms by which smoking may
      initiate and maintain oxidative stress at periodontally healthy sites and
      participate in disease progression, by reducing innate immune responses.

PMID- 22607097
TI  - Variation in floral longevity in the genus Leptosiphon: mating system
      consequences.
AB  - Pollination or fertilisation trigger floral senescence in a wide range of
      flowering plants, and yet little attention has been given to the implications of
      this phenomenon to mating system evolution. We examined the effects of
      pollination on floral senescence in the genus Leptosiphon. Species in the genus
      exhibit a wide range of breeding systems. In all cases, compatible pollination
      induced senescence; emasculated flowers lived longer than hand-outcrossed
      flowers. In the self-compatible species, Leptosiphon acicularis and L. bicolor,
      and in one highly selfing population of L. jepsonii, unmanipulated flowers had
      reduced longevity compared to emasculated flowers, suggesting that autonomous
      self-pollination limits floral longevity in these species. Limited floral
      longevity in these highly selfing taxa may reduce opportunities for male outcross
      success, representing a possible source of selection on the mating system. In
      turn, the mating system might influence how selection acts on floral longevity;
      obligately outcrossing taxa are expected to benefit from longer floral
      longevities to maximise opportunities for pollination, while selfing taxa might
      benefit from earlier floral senescence to reduce resource expenditure. Overall,
      the longevity of unpollinated flowers increased with the level of outcrossing in
      the genus Leptosiphon. Our results taken together with those of a previous study
      and similar results in other species suggest that floral longevity may represent
      a largely unexamined role in mating system evolution.

PMID- 22607098
TI  - De novo assembly and characterization of bark transcriptome using Illumina
      sequencing and development of EST-SSR markers in rubber tree (Hevea brasiliensis
      Muell. Arg.).
AB  - BACKGROUND: In rubber tree, bark is one of important agricultural and biological
      organs. However, the molecular mechanism involved in the bark formation and
      development in rubber tree remains largely unknown, which is at least partially
      due to lack of bark transcriptomic and genomic information. Therefore, it is
      necessary to carried out high-throughput transcriptome sequencing of rubber tree
      bark to generate enormous transcript sequences for the functional
      characterization and molecular marker development. RESULTS: In this study, more
      than 30 million sequencing reads were generated using Illumina paired-end
      sequencing technology. In total, 22,756 unigenes with an average length of 485 bp
      were obtained with de novo assembly. The similarity search indicated that 16,520
      and 12,558 unigenes showed significant similarities to known proteins from NCBI
      non-redundant and Swissprot protein databases, respectively. Among these
      annotated unigenes, 6,867 and 5,559 unigenes were separately assigned to Gene
      Ontology (GO) and Clusters of Orthologous Group (COG). When 22,756 unigenes
      searched against the Kyoto Encyclopedia of Genes and Genomes Pathway (KEGG)
      database, 12,097 unigenes were assigned to 5 main categories including 123 KEGG
      pathways. Among the main KEGG categories, metabolism was the biggest category
      (9,043, 74.75%), suggesting the active metabolic processes in rubber tree bark.
      In addition, a total of 39,257 EST-SSRs were identified from 22,756 unigenes, and
      the characterizations of EST-SSRs were further analyzed in rubber tree. 110
      potential marker sites were randomly selected to validate the assembly quality
      and develop EST-SSR markers. Among 13 Hevea germplasms, PCR success rate and
      polymorphism rate of 110 markers were separately 96.36% and 55.45% in this study.
      CONCLUSION: By assembling and analyzing de novo transcriptome sequencing data, we
      reported the comprehensive functional characterization of rubber tree bark. This
      research generated a substantial fraction of rubber tree transcriptome sequences,
      which were very useful resources for gene annotation and discovery, molecular
      markers development, genome assembly and annotation, and microarrays development
      in rubber tree. The EST-SSR markers identified and developed in this study will
      facilitate marker-assisted selection breeding in rubber tree. Moreover, this
      study also supported that transcriptome analysis based on Illumina paired-end
      sequencing is a powerful tool for transcriptome characterization and molecular
      marker development in non-model species, especially those with large and complex
      genomes.

PMID- 22607100
TI  - Effects of coupled plasma filtration adsorption on septic patients with multiple
      organ dysfunction syndrome.
AB  - AIM: The aim of this study was to observe the effects of coupled plasma
      filtration adsorption (CPFA) on septic patients with multiple organ dysfunction
      syndrome (MODS). METHODS: A total of 14 patients were randomly divided into two
      groups, and, respectively, received 10 h of CPFA or high-volume hemofiltration
      (HVHF). The mean arterial pressure (MAP), electrolytes and acid-base balance, the
      sequential organ failure assessment (SOFA) score, and the acute physiology and
      chronic health evaluation II (APACHE II) score were analyzed. Serum levels of
      high-mobility group box-1 (HMGB-1) protein, tumor necrosis factor-alpha (TNF
      alpha), and intercellular adhesion molecule-1 (ICAM-1) were also measured by
      enzyme-linked immunosorbent assay. RESULTS: After CPFA and HVHF, temporary
      reduction in blood urea nitrogen and serum creatinine, electrolytes and acid-base
      metabolism balance were well maintained. Both the SOFA and the APACHE II scores
      were markedly reduced after CPFA (p < 0.01), while only the SOFA score was
      significantly decreased after HVHF (p < 0.05). After 10-h treatment with CPFA,
      the MAP and oxygen index (PaO(2)/FiO(2)) were significantly higher than those at
      0 h. Furthermore, the serum levels of HMGB-1, ICAM-1, and TNF-alpha decreased
      after 10 h of CPFA (p < 0.05), while the serum levels of HMGB-1 declined at 5 h
      of HVHF, but rebounded at 10 h, and the serum levels of TNF-alpha and ICAM-1 were
      no significant change after treatment with HVHF. CONCLUSIONS: The study indicated
      that CPFA could be superior to HVHF in improving the clinical manifestations and
      eliminating inflammatory mediators, which had implications in the optimal
      treatment of septic patients with MODS.

PMID- 22607101
TI  - Optimization of PLGA nanoparticles formulation containing L-DOPA by applying the
      central composite design.
AB  - The aim of this work was to prepare L-DOPA loaded poly(D,L-lactide-co-glycolide)
      (PLGA) nanoparticles by a modified water-in-oil-in-water (W(1)/O/W(2))
      emulsification solvent evaporation method. A central composite design was applied
      for optimization of the formulation parameters and for studying the effects of
      three independent variables: PLGA concentration, polyvinyl alcohol (PVA)
      concentration and organic solvent removal rate on the particle size and the
      entrapment efficiency (response variables). Second-order models were obtained to
      adequately describe the influence of the independent variables on the selected
      responses. The analysis of variance showed that the three independent variables
      had significant effects (p < 0.05) on the responses. The experimental results
      were in perfect accordance with the predictions estimated by the models. Using
      the desirability approach and overlay contour plots, the optimal preparation area
      can be highlighted. It was found that the optimum values of the responses could
      be obtained at higher concentration of PLGA (5%, w/v) and PVA (6%, w/v); and
      faster organic solvent removal rate (700 rpm). The corresponding particle size
      was 256.2 nm and the entrapment efficiency was 62.19%. FTIR investigation
      confirmed that the L-DOPA and PLGA polymer maintained its backbone structure in
      the fabrication of nanoparticles. The scanning electron microscopic images of
      nanoparticles showed that all particles had spherical shape with porous outer
      skin. The results suggested that PLGA nanoparticles might represent a promising
      formulation for brain delivery of L-DOPA. The preparation of L-DOPA loaded PLGA
      nanoparticles can be optimized by the central composite design.

PMID- 22607102
TI  - Nutritional screening tools as predictors of mortality, functional decline, and
      move to higher level care in older people: a systematic review.
AB  - This systematic review assessed whether nutritional screening tools (NSTs)
      predict mortality, functional decline, and move to higher level care in older
      adults residing in the community or in institutions. In total, 37 prospective
      studies published between 1999 and 2012 met inclusion criteria and were included
      in this review. The most commonly used NST in these studies was the Mini
      Nutritional Assessment (MNA). Comparison of NSTs was limited by variation in
      follow-up time, lack of uniform definition of functional decline, and biases in
      many studies. Results of MNA, MNA-Short Form (MNA-SF), and Geriatric Nutrition
      Risk Index (GNRI) assessments were significantly associated with subsequent
      mortality, with good negative predictive power (~0.83), but only modest positive
      predictive power (PPV~0.32). MNA-SF and MNA results had a low to moderate
      association with functional decline (PPV~0.34). Move to higher level care was
      less strongly associated with NST scores (PPV~0.25). Overall, there is evidence
      that NSTs can predict those at low risk of mortality, functional decline, and, to
      a lesser extent, move to higher level care in older people.

PMID- 22607103
TI  - Multiple point-of-testing nutrition counseling sessions reduce risk factors for
      chronic disease among older adults.
AB  - The objectives of this study were to explore the relationships of baseline
      dietary intakes and frequency of attendance at point-of-testing nutrition
      counseling sessions to selected risk factors for chronic diseases during a 3-year
      intervention. This study was part of a large multidisciplinary, community-based
      health outreach project conducted in a rural community of northern Louisiana.
      Screenings, point-of-testing counseling, weekly group exercise sessions, and
      group nutrition education sessions were provided over a period of 3 years.
      Outcome variables assessed at 6-month intervals over 3 years were body mass index
      (BMI), systolic and diastolic blood pressure, fasting blood glucose, and total
      and LDL cholesterol and dietary intake. Repeated measure analysis of variance was
      used to investigate the impact of the frequency of counseling sessions on outcome
      variables. Paired t-tests were used to identify points at which significant
      changes occurred. A total of 159 subjects ages 65 years and older participated in
      this study. The majority of the participants were female (62%) and White (82%).
      Attending the point of testing counseling for more than two sessions was
      important for a significant improvement in BMI (p <= 0.001), LDL cholesterol (p
      <= 0.03), blood glucose (p <= 0.03), and diastolic blood pressure (p <= 0.045).
      Participants who attended at least three sessions had significant reductions in
      risk factors for obesity and related chronic diseases, underscoring the
      importance of follow-up sessions after health screening.

PMID- 22607104
TI  - Ensuring vitamin D supplementation in nursing home patients--a quality
      improvement project.
AB  - Randomized controlled trials have shown that adequate vitamin D supplementation
      in nursing home (NH) residents reduces the rates of falls and fractures. In our
      NH, review of medication administration records of all patients (n = 101)
      revealed that only 34.6% of the patients were currently prescribed adequate doses
      of vitamin D, revealing a need for intervention. We designed a Quality
      Improvement (QI) project with the objective of improving the vitamin D
      prescription rate in our NH. We used the Plan-Do-Study-Act (PDSA) approach to
      implement this QI project. Patients not currently prescribed an adequate dose of
      vitamin D were identified and started on a daily dose of 800 IU of vitamin D.
      Additionally, patients who were experiencing falls while on an adequate dose of
      vitamin D for 3 months were examined for the possibility of vitamin D deficiency
      and were started on 50,000 IU of vitamin D per week for 12 weeks if they were
      found to be vitamin D-deficient based on blood levels of 25-hydroxy-vitamin D
      below 30 ng/mL. We found that with several PDSA cycles over a period of 5 months,
      the prescription rate for vitamin D was increased to 86%, surpassing our initial
      goal of 80%. In conclusion, we found that a multidisciplinary QI program
      utilizing multiple PDSA cycles was effective in reaching target prescription
      rates for vitamin D supplementation in a population of NH patients.

PMID- 22607106
TI  - Aggregation of BioGlue((r)) presenting as a right atrial mass: a case report.
AB  - Use of biological glue during cardiovascular surgery is a common practice, rarely
      associated with immediate or long-term complications. We present a patient with a
      right atrial mass as a long-term complication associated with the use of
      biological glue. Surgical exploration revealed the mass to be an unabsorbed and
      infected aggregate of biological glue used to stop bleeding from a friable right
      atrium during previous surgery.

PMID- 22607105
TI  - Determinants of uncontrolled hypertension in adult type 2 diabetes mellitus: an
      analysis of the Malaysian diabetes registry 2009.
AB  - BACKGROUND: Uncontrolled blood pressure (BP) is a significant contributor of
      morbidity and even mortality in type 2 diabetes (T2D) patients. This study was
      done to determine the significant determinants of uncontrolled blood pressure in
      T2D patients in Malaysia. METHODS: Between 1st January 2009 to 31st December
      2009, data from 70 889 patients with Type 2 diabetes was obtained from the Adult
      Diabetes Control and Management Registry for analysis; 303 centers participated
      in the study. Their demographic characteristics, the nature of their diabetes,
      their state of hypertension, treatment modalities, risk factors, and
      complications are described. Based on their most recent BP values, subjects were
      divided into controlled BP and uncontrolled BP and their clinical determinants
      compared. Independent determinants were identified using multivariate logistic
      regression. RESULTS: The mean age of patients at diagnosis of diabetes was 52.3
      +/- 11.1 years old. Most were women (59.0 %) and of Malay ethnicity (61.9 %). The
      mean duration of diabetes was 5.9 +/- 5.6 years. A total of 57.4 % were
      hypertensive. Of the 56 503 blood pressure (BP) measured, 13 280 (23.5 %)
      patients had BP <130/80 mmHg. Eighteen percent was on > two anti-hypertensive
      agents. Health clinics without doctor, older age (>= 50 years old), shorter
      duration of diabetes (< 5 years), Malay, overweight were determinants for
      uncontrolled blood pressure (BP >=130/80 mmHg). Patients who were on anti
      hypertensive agent/s were 2.7 times more likely to have BP >=130/80 mmHg. Type 2
      diabetes patients who had ischaemic heart disease or nephropathy were about 20 %
      and 15 % more likely to have their blood pressure treated to target respectively.
      CONCLUSIONS: Major independent determinants of uncontrolled BP in our group of
      T2D patients were Malay ethnicity, older age, recent diagnosis of diabetes,
      overweight and follow-up at health clinics without a doctor and possibly the
      improper use of anti hypertensive agent. More effort, education and resources,
      especially in the primary health care centres are needed to improve hypertensive
      care among our patients with diabetes.

PMID- 22607107
TI  - Intraoperative photodynamic therapy: a description of a new adjuvant technique
      for patients with nonmelanoma skin cancer.

PMID- 22607099
TI  - Thioredoxin and thioredoxin target proteins: from molecular mechanisms to
      functional significance.
AB  - The thioredoxin (Trx) system is one of the central antioxidant systems in
      mammalian cells, maintaining a reducing environment by catalyzing electron flux
      from nicotinamide adenine dinucleotide phosphate through Trx reductase to Trx,
      which reduces its target proteins using highly conserved thiol groups. While the
      importance of protecting cells from the detrimental effects of reactive oxygen
      species is clear, decades of research in this field revealed that there is a
      network of redox-sensitive proteins forming redox-dependent signaling pathways
      that are crucial for fundamental cellular processes, including metabolism,
      proliferation, differentiation, migration, and apoptosis. Trx participates in
      signaling pathways interacting with different proteins to control their dynamic
      regulation of structure and function. In this review, we focus on Trx target
      proteins that are involved in redox-dependent signaling pathways. Specifically,
      Trx-dependent reductive enzymes that participate in classical redox reactions and
      redox-sensitive signaling molecules are discussed in greater detail. The latter
      are extensively discussed, as ongoing research unveils more and more details
      about the complex signaling networks of Trx-sensitive signaling molecules such as
      apoptosis signal-regulating kinase 1, Trx interacting protein, and phosphatase
      and tensin homolog, thus highlighting the potential direct and indirect impact of
      their redox-dependent interaction with Trx. Overall, the findings that are
      described here illustrate the importance and complexity of Trx-dependent, redox
      sensitive signaling in the cell. Our increasing understanding of the components
      and mechanisms of these signaling pathways could lead to the identification of
      new potential targets for the treatment of diseases, including cancer and
      diabetes.

PMID- 22607108
TI  - Stereoselective synthesis and relative configuration assignment of gabosine J.
AB  - The first total synthesis of (+)-gabosine J and that of the epimer at C4 of its
      enantiomer have been accomplished through an enantioselective approach from a
      common intermediate 1. These syntheses have allowed us to establish the correct
      relative configuration of the natural metabolite, which was originally
      misassigned. This work, together with our former syntheses of other gabosines and
      related compounds, validates enone 1 as a general synthetic precursor for this
      kind of carbasugars.

PMID- 22607110
TI  - Doxorubicin and chloroquine coencapsulated liposomes: preparation and improved
      cytotoxicity on human breast cancer cells.
AB  - Doxorubicin, as a widely used chemotherapeutic, always causes multidrug
      resistance in human cancer cells. To circumvent drug resistance, we developed a
      novel formulation where doxorubicin hydrochloride (DOX) and chloroquine phosphate
      (CQ) were simultaneously loaded into liposomes by a pH-gradient method where CQ
      played the role of a chemical sensitizer. The various factors were investigated
      to optimize the formulation and manufacturing conditions of DOX and CQ
      coencapsulated liposomes (DCL). The resultant DCLs achieved the high
      encapsulation efficiency of both drugs over 90%. Further, DCLs significantly
      displayed resistance reversal action on a doxorubicin-resistant human breast
      cancer cell line (MCF-7/ADR) through the cooperation of CQ with DOX. The reversal
      fold of DCL with the DOX/CQ/soybean phosphatidylcholine weight ratio of 0.5:1:50
      was 5.7, compared to free DOX. These results demonstrate that DCL is a promising
      formulation for the treatment of DOX-resistant breast cancer.

PMID- 22607109
TI  - A 4-week, dose-ranging study comparing the efficacy, safety and tolerability of
      latanoprost 75, 100 and 125 MUg/mL to latanoprost 50 MUg/mL (xalatan) in the
      treatment of primary open-angle glaucoma and ocular hypertension.
AB  - BACKGROUND: Several studies have investigated the effect of latanoprost on
      intraocular pressure (IOP). We compared the IOP-lowering effects of three higher
      concentrations of latanoprost with the commercially available concentration of
      0.005% (50 MUg/mL) in patients with primary open-angle glaucoma or ocular
      hypertension. METHODS: Treatment-naive subjects or those receiving IOP-lowering
      medication with baseline IOP levels of >= 24 mmHg and <= 36 mmHg in at least one
      eye after washout were randomized to receive an evening dose of latanoprost 50,
      75, 100, or 125 MUg/mL for 4 weeks. At weeks 1, 2, 3, and 4, ocular examinations
      were performed and IOP was measured. Ocular symptoms and adverse events were
      monitored. The primary efficacy endpoint was the change in IOP from baseline to
      week 4 at 8 a.m. and 4 p.m. for the per protocol (PP) population using a "worse
      eye" analysis. Secondary efficacy endpoints were change in IOP at each time point
      from baseline across all visits, and percentage change in IOP from baseline to
      week 4 at 8 a.m. RESULTS: In all, 282 patients were randomized and treated; 274
      were included in the PP population. Treatment groups were similar at baseline;
      68% were diagnosed with primary open-angle glaucoma. Mean baseline IOP levels
      were comparable across treatments. There were no statistically significant
      differences in IOP reductions from baseline to week 4 at either time point
      between those treated with higher concentrations of latanoprost versus those
      receiving 50 MUg/mL. Least squares mean IOP changes at 8 a.m. were -10.13, -9.59,
      -10.02, and -9.06 mmHg for latanoprost 50, 75, 100, and 125 MUg/mL, respectively,
      and at 4 p.m. were -8.90, -8.29, -8.81, and -8.34 mmHg, respectively. Results of
      secondary efficacy analyses supported those of the primary analysis. Conjunctival
      hyperemia, the most commonly reported adverse event, occurred in 16.9%, 18.6%,
      20.8% and 15.9% of subjects receiving latanoprost 50, 75, 100, and 125 MUg/mL,
      respectively. CONCLUSIONS: IOP reductions were observed in all treatment groups
      postbaseline, with no clinically relevant or statistically significant
      differences detected favoring any of the higher concentrations of latanoprost
      compared with latanoprost 50 MUg/mL. All doses of latanoprost were well
      tolerated. TRIAL REGISTRATION: Clinical Trials.gov Identifier NCT01379144.

PMID- 22607111
TI  - Influence of anti-asthmatic medications on dental caries in children in Slovenia.
AB  - OBJECTIVE.  The study investigated the influence of exposure to anti-asthmatic
      medications and of various factors on the caries prevalence in children in
      Slovenia. METHODS.  The study population consisted of children aged 2 to 17 years
      (n = 220) under treatment for asthma, who had used anti-asthmatic medications for
      at least 1 year; 220 controls were matched for age. Caries status was determined
      by the number of decayed, missing, and filled surfaces through clinical
      examination by two calibrated dentists using the International Caries Detection
      and Assessment System-II scoring criteria. Questionnaires completed by parents
      and data from the patients' medical records provided information on various
      confounding factors. RESULTS.  Asthmatic children had significantly higher (P <=
      0.01) prevalence of caries on primary and permanent teeth in all age groups, and
      the proportion of caries-free children was significantly smaller (P <= 0.05). In
      multivariate regression analysis, asthma diagnosis, child's age, daily use of
      inhaled glucocorticoids, length and frequency of medicine application, spacer
      use, mouth rinsing with water after medicine application, parents' education,
      frequent food and drink consumption, and frequency of toothbrushing were
      associated with caries experience of asthmatic children. CONCLUSION.  Children
      with asthma who had used anti-asthmatic medications had higher caries experience
      in primary and permanent teeth.

PMID- 22607112
TI  - Global burden of injuries attributable to alcohol consumption in 2004: a novel
      way of calculating the burden of injuries attributable to alcohol consumption.
AB  - BACKGROUND: Alcohol consumption is a major risk factor for injuries; however,
      international data on this burden are limited. This article presents new methods
      to quantify the burden of injuries attributable to alcohol consumption and
      quantifies the number of deaths, potential years of life lost (PYLL), and
      disability-adjusted life years (DALYs) lost from injuries attributable to alcohol
      consumption for 2004. METHODS: Data on drinking indicators were obtained from the
      Comparative Risk Assessment study. Data on mortality, PYLL, and DALYs for
      injuries were obtained from the World Health Organization. Alcohol-attributable
      fractions were calculated based on a new risk modeling methodology, which
      accounts for average and heavy drinking occasions. 95% confidence intervals (CIs)
      were calculated using a Monte Carlo simulation method. RESULTS: In 2004, 851,900
      (95% CI: 419,400 to 1,282,500) deaths, 19,051,000 (95% CI: 9,767,000 to
      28,243,000) PYLL, and 21,688,000 (95% CI: 11,097,000 to 32,385,000) DALYs for
      people 15 years and older were due to injuries attributable to alcohol
      consumption. With respect to the total number of deaths, harms to others were
      responsible for 15.1% of alcohol-attributable injury deaths, 14.5% of alcohol
      attributable injury PYLL, and 11.35% of alcohol-attributable injury DALYs. The
      overall burden of injuries attributable to alcohol consumption corresponds to
      17.3% of all injury deaths, 16.7% of all PYLL, and 13.6% of all DALYs caused by
      injuries, or 1.4% of all deaths, 2.0% of all PYLL, and 1.4% of all DALYs in 2004.
      CONCLUSIONS: The novel methodology described in this article to calculate the
      burden of injuries attributable to alcohol consumption improves on previous
      methodology by more accurately calculating the burden of injuries attributable to
      one's own drinking, and for the first time, calculates the burden of injuries
      attributable to the alcohol consumption of others. The burden of injuries
      attributable to alcohol consumption is large and is entirely avoidable, and
      policies and strategies to reduce it are recommended.

PMID- 22607113
TI  - Effect of a LoBAG30 diet on protein metabolism in men with type 2 diabetes. A
      Randomized Controlled Trial.
AB  - BACKGROUND: We previously reported that a weight-maintenance diet with a
      carbohydrate:protein:fat ratio of 30:30:40%, ingested for 5 weeks, improved blood
      glucose control in subjects with untreated type 2 diabetes. In this study we also
      determined that insulin and insulin-like growth factor-I (IGF-I) were increased.
      In this report we provide further information. Specifically, 24-hour total and
      individual amino acids, glucagon and cortisol data are provided. In addition, we
      determined whether these multiple effectors resulted in a positive nitrogen
      balance and an increase in fat-free mass. Insulin and IGF-I should stimulate
      protein accumulation. An increase in amino acids, particularly branched chain
      amino acids, should facilitate this, whereas glucagon and cortisol could have
      adverse effects in this regard. METHODS: Eight men with untreated type 2 diabetes
      were studied. A randomized crossover design was used. Data were obtained before
      and after 5 weeks on a control diet (55% carbohydrate:15% protein:30% fat) and on
      a 30% carbohydrate:30% protein:40% fat diet. Nitrogen balance and body
      composition were determined at the beginning and end of each dietary
      intervention. RESULTS: As expected, the mean 24-hour total amino acid area
      response was higher after ingesting the 30:30:40 diet. However, the increase was
      only statistically significant for the branched chain amino acids, and
      phenylalanine and tyrosine. The 24-hour cortisol profile was unchanged. Glucagon
      was increased. Nitrogen balance was positive. Body weight was stable. Body
      composition and computed tomography data indicate no change in the fat-free mass.
      CONCLUSION: This high protein, low carbohydrate diet induced a metabolic milieu
      which strongly favors a positive protein balance, and a positive balance was
      present. However, an increase in lean (protein) mass was not documented. Whether
      such a diet in people with type 2 diabetes is useful in preventing or delaying
      the loss of total lean body mass and/or sarcopenia associated with aging remains
      to be determined.

PMID- 22607114
TI  - Synthetic principles directing charge transport in low-band-gap dithienosilole
      benzothiadiazole copolymers.
AB  - Given the fundamental differences in carrier generation and device operation in
      organic thin-film transistors (OTFTs) and organic photovoltaic (OPV) devices, the
      material design principles to apply may be expected to differ. In this respect,
      designing organic semiconductors that perform effectively in multiple device
      configurations remains a challenge. Following "donor-acceptor" principles, we
      designed and synthesized an analogous series of solution-processable pi
      conjugated polymers that combine the electron-rich dithienosilole (DTS) moiety,
      unsubstituted thiophene spacers, and the electron-deficient core 2,1,3
      benzothiadiazole (BTD). Insights into backbone geometry and wave function
      delocalization as a function of molecular structure are provided by density
      functional theory (DFT) calculations at the B3LYP/6-31G(d,p) level. Using a
      combination of X-ray techniques (2D-WAXS and XRD) supported by solid-state NMR
      (SS-NMR) and atomic force microscopy (AFM), we demonstrate fundamental
      correlations between the polymer repeat-unit structure, molecular weight
      distribution, nature of the solubilizing side-chains appended to the backbones,
      and extent of structural order attainable in p-channel OTFTs. In particular, it
      is shown that the degree of microstructural order achievable in the self
      assembled organic semiconductors increases largely with (i) increasing molecular
      weight and (ii) appropriate solubilizing-group substitution. The corresponding
      field-effect hole mobilities are enhanced by several orders of magnitude,
      reaching up to 0.1 cm(2) V(-1) s(-1) with the highest molecular weight fraction
      of the branched alkyl-substituted polymer derivative in this series. This trend
      is reflected in conventional bulk-heterojunction OPV devices using PC(71)BM,
      whereby the active layers exhibit space-charge-limited (SCL) hole mobilities
      approaching 10(-3) cm(2) V(-1) s(-1), and yield improved power conversion
      efficiencies on the order of 4.6% under AM1.5G solar illumination. Beyond
      structure-performance correlations, we observe a large dependence of the
      ionization potentials of the polymers estimated by electrochemical methods on
      polymer packing, and expect that these empirical results may have important
      consequences on future material study and device applications.

PMID- 22607115
TI  - Principle-based analysis of the concept of telecare.
AB  - AIM: To report a concept analysis of telecare. BACKGROUND: Lately telecare has
      become a worldwide, modern way of giving care over distance by means of
      technology. Other concepts, like telemedicine, e-health, and telehealth, focus on
      the same topic though the boundaries between them seem to be blurred. DATA
      SOURCES: Sources comprise 44 English language research articles retrieved from
      the database of Medline and Cinahl (1995-October 2011). DESIGN: Literature
      Review. METHOD: A principle-based analysis was undertaken through content
      analysis of the definitions, attributes, preconditions, and outcomes of the
      concept. RESULTS: The attributes are well described according to the use of
      technology, caring activity, persons involved, and accessibility. Preconditions
      and outcomes are well described concerning individual and health political needs
      and benefits. The concept did not hold its boundaries through theoretical
      integration with the concept of telemedicine and telehealth. The definition of
      telecare competes with concepts like home-based e-health, telehomecare,
      telephonecare, telephone-based psychosocial services, telehealth, and
      telemedicine. Assessment of the definitions resulted in a suggestion of a new
      definition: Telecare is the use of information, communication, and monitoring
      technologies which allow healthcare providers to remotely evaluate health status,
      give educational intervention, or deliver health and social care to patients in
      their homes. CONCLUSION: The logical principle was assessed to be partly
      immature, whereas the pragmatical and linguistical principles were found to be
      mature. A new definition is suggested and this has moved the epistemological
      principle forward to maturity.

PMID- 22607116
TI  - Risk factors for bruxism among Croatian navy employees.
AB  - The aim of the study was to evaluate the relationship between bruxism, and
      sociodemographic parameters, symptoms of temporomandibular disorders (TMD),
      personality and war experience among Croatian navy employees. The sample included
      1092 subjects, aged 20-60 years (mean age 37.06 +/- 7.85). An individual's
      bruxism status was based on clinical oral examination and participants' report of
      bruxism. Subjects with bruxism index values >= 90th percentile were included in
      severe bruxism group (n = 111), and those with scores below 90th percentile were
      labelled as negligible bruxism group (n = 981). No differences were found in
      gender distribution between the two groups. The proportion of military personnel
      presenting with bruxism is double the proportion of administrative employees with
      bruxism. A total of 23.34% subjects in negligible bruxism group and 48.65% in
      severe bruxism group participated in the war. Subjects in severe bruxism group
      presented more TMD-related signs and symptoms than those in negligible bruxism
      group. Higher prevalence of neuroticism and psychoticism was found in severe
      bruxism group. According to logistic regression, the probability of severe
      bruxism was significantly associated with marital status [Odds ratio (OR) 6.859,
      95% confidence interval (CI) 3.869-12.158 P < 0.001], neuroticism (OR 2.842, 95%
      CI 1.434-5.632 P = 0.003), psychoticism (OR 2.618, 95% CI 1.193-5.746 P = 0.016),
      military duty (OR 1.828, 95% CI 1.013-3.298 P = 0.045) and masticatory muscles
      tenderness (OR 9.372, 95% CI 4.923-17.841 P < 0.001). Smokers had a 2.72-fold
      (95% CI 1.706-4.335 P < 0.001) higher risk of bruxism than non-smokers. Subjects
      who participated in war were more represented in severe bruxism group. Further
      studies, including other potential risk factors, are required to clarify these
      relationships.

PMID- 22607117
TI  - Polyphenols decreased liver NADPH oxidase activity, increased muscle
      mitochondrial biogenesis and decreased gastrocnemius age-dependent autophagy in
      aged rats.
AB  - This study explored major systems of reactive oxygen species (ROS) production and
      their consequences on oxidative stress, mitochondriogenesis and muscle metabolism
      in aged rats, and evaluated the efficiency of 30-day oral supplementation with a
      moderate dose of a red grape polyphenol extract (RGPE) on these parameters. In
      the liver of aged rats, NADPH oxidase activity was increased and mitochondrial
      respiratory chain complex activities were altered, while xanthine oxidase
      activity remained unchanged. In muscles, only mitochondrial activity was modified
      with aging. The oral intake of RGPE decreased liver NADPH oxidase activity in the
      aged rats without affecting global oxidative stress, suggesting that NADPH
      oxidase was probably not the dominant detrimental source of production of O(2).(
      ) in the liver. Interestingly, RGPE supplementation increased mitochondrial
      biogenesis and improved antioxidant status in the gastrocnemius of aged rats,
      while it had no significant effect in soleus. RGPE supplementation also decreased
      age-dependent autophagy in gastrocnemius of aged rats. These results extended
      existing findings on the beneficial effects of RGPE on mitochondriogenesis and
      muscle metabolism in aged rats.

PMID- 22607118
TI  - Potential role of proinflammatory cytokines in the pathogenetic mechanisms of
      vascular lesions in goats naturally infected with bluetongue virus serotype 1.
AB  - In vitro studies have demonstrated that bluetongue virus (BTV)-induced vasoactive
      mediators could contribute to the endothelial cells dysfunction and increased
      vascular permeability responsible of lesions characteristic of bluetongue (BT)
      like oedema, haemorrhages and ischaemic necrosis in different tissues. However,
      few in vivo studies have been carried out to clarify the causes of these lesions.
      The aim of this study was to elucidate in vivo the pathogenetic mechanisms
      involved in the appearance of vascular lesions in different organs during BT. For
      this purpose, tissue samples from goats naturally infected with bluetongue virus
      serotype 1 (BTV-1) were taken for histopathological and immunohistochemical
      studies to determine the potential role of proinflammatory cytokines (tumour
      necrosis factor alpha, TNFalpha and interleukin one alpha, IL-1alpha) in the
      increased vascular permeability and their relationship with the presence of
      virus. Gross and histopathological examination revealed the presence of vascular
      damage leading to generalized oedema and haemorrhages. Immunohistochemical
      studies displayed that endothelial injury may have been due to the direct
      pathogenic effect of BTV infection on endothelial cells or may be a response to
      inflammatory mediators released by virus-infected endothelial cells and,
      possibly, other cell types such as monocytes/macrophages. These preliminary
      results of what appears to be the first in vivo study of tissue damage in small
      BT-infected ruminants suggest a direct link between the appearance of vascular
      changes and the presence of BTV-induced vasoactive cytokines.

PMID- 22607119
TI  - RNA-seq analysis of differential gene expression in liver from lactating dairy
      cows divergent in negative energy balance.
AB  - BACKGROUND: The liver is central to most economically important metabolic
      processes in cattle. However, the changes in expression of genes that drive these
      processes remain incompletely characterised. RNA-seq is the new gold standard for
      whole transcriptome analysis but so far there are no reports of its application
      to analysis of differential gene expression in cattle liver. We used RNA-seq to
      study differences in expression profiles of hepatic genes and their associated
      pathways in individual cattle in either mild negative energy balance (MNEB) or
      severe negative energy balance (SNEB). NEB is an imbalance between energy intake
      and energy requirements for lactation and body maintenance. This aberrant
      metabolic state affects high-yielding dairy cows after calving and is of
      considerable economic importance because of its negative impact on fertility and
      health in dairy herds. Analysis of changes in hepatic gene expression in SNEB
      animals will increase our understanding of NEB and contribute to the development
      of strategies to circumvent it. RESULTS: RNA-seq analysis was carried out on
      total RNA from liver from early post partum Holstein Friesian cows in MNEB (n =
      5) and SNEB (n = 6). 12,833 genes were deemed to be expressed (>4 reads per gene
      per animal), 413 of which were shown to be statistically significantly
      differentially expressed (SDE) at a false discovery rate (FDR) of 0.1% and 200 of
      which were SDE (FDR of 0.1%) with a >= 2-fold change between MNEB and SNEB
      animals. GOseq/KEGG pathway analysis showed that SDE genes with >= 2- fold change
      were associated (P <0.05) with 9 KEGG pathways. Seven of these pathways were
      related to fatty acid metabolism and unexpectedly included 'Steroid hormone
      biosynthesis', a process which mainly occurs in the reproductive organs rather
      than the liver. CONCLUSIONS: RNA-seq analysis showed that the major changes at
      the level of transcription in the liver of SNEB cows were related to fat
      metabolism. 'Steroid hormone biosynthesis', a process that normally occurs in
      reproductive tissue, was significantly associated with changes in gene expression
      in the liver of SNEB cows. Changes in gene expression were found in this pathway
      that have not been previously been identified in SNEB cows.

PMID- 22607120
TI  - Quantification of skin penetration of antioxidants of varying lipophilicity.
AB  - Antioxidants play a vital role in protecting the skin from environmental
      distress. As the skin is constantly exposed to harmful UV radiation, endogenous
      antioxidants present in the superficial layers of the skin neutralize reactive
      oxygen species. Over time, antioxidants become depleted and loss their protective
      effect on the skin. Therefore, supplementing skin with topical antioxidant can
      help replenish this loss and fight the oxidative stress. The objective of this
      study was to deliver antioxidants topically and quantify the amount permeated in
      the stratum corneum and underlying skin. Polyphenols (catechin, resveratrol and
      curcumin) and vitamin (retinol) with various lipophilic properties were delivered
      via porcine ear skin, using propylene glycol as a vehicle. The amount in the
      stratum corneum and underlying skin was quantified using tape stripping and skin
      extraction methods, respectively, and samples were analysed via HPLC. All four
      antioxidants permeated into the skin from the propylene glycol vehicle. The order
      of the amount of antioxidant in the stratum corneum was catechin > resveratrol~
      retinol> curcumin, whereas that in the underlying skin was retinol > catechin~
      resveratrol~ curcumin. Of the total amount of polyphenols in the skin,
      approximately 90% was retained in the stratum corneum whereas 10% was quantified
      in the underlying skin. In contrast, 10% of retinol was retained in the stratum
      corneum whereas 90% permeated in the underlying skin. Polyphenols (catechin,
      resveratrol and curcumin) showed high concentration in the stratum corneum
      whereas retinol showed high accumulation in the underlying layers of the skin.

PMID- 22607121
TI  - Pyrolysis products of linear alkylbenzenes--implications in fire debris analysis.
AB  - In this case report, potential interferences from an improvised fire
      extinguishing agent, a dishwashing liquid, containing linear alkylbenzene
      sulfonates (LAS), was studied. The presence of linear alkylbenzenes (LABs) in the
      fire debris sample was identified from the summed ion profile (SIP) analysis. It
      was found that the LAS from dishwashing liquids produce LABs by thermal
      degradation. Direct pyrolysis of a LAS-containing dishwashing liquid at 300
      degrees C yielded a distribution of LABs in the SIP. LABs began to break down at
      pyrolysis temperatures between 450 and 500 degrees C and completely break down by
      800 degrees C. Observed pyrolysis breakdown products of LABs included toluene,
      ethylbenzene, meta-, para-, and ortho-xylenes, propylbenzene, indane,
      naphthalene, and 1- and 2-methylnaphthalenes. These data suggested the presence
      of LABs in fire debris evidence might complicate subsequent analysis because
      their breakdown products contained some of the target compounds common to
      ignitable liquid identification. Therefore, a positive determination of the
      presence of foreign ignitable liquids should be carefully evaluated when there is
      a presence of LABs in the SIP.

PMID- 22607122
TI  - Discovery of highly potent human deoxyuridine triphosphatase inhibitors based on
      the conformation restriction strategy.
AB  - Human deoxyuridine triphosphatase (dUTPase) inhibition is a promising approach to
      enhance the efficacy of thymidylate synthase (TS) inhibitor based chemotherapy.
      In this study, we describe the discovery of a novel class of human dUTPase
      inhibitors based on the conformation restriction strategy. On the basis of the X
      ray cocrystal structure of dUTPase and its inhibitor compound 7, we designed and
      synthesized two conformation restricted analogues, i.e., compounds 8 and 9. These
      compounds exhibited increased in vitro potency compared with the parent compound
      7. Further structure-activity relationship (SAR) studies identified a compound 43
      with the highest in vitro potency (IC(50) = 39 nM, EC(50) = 66 nM). Furthermore,
      compound 43 had a favorable oral PK profile and exhibited potent antitumor
      activity in combination with 5-fluorouracil (5-FU) in the MX-1 breast cancer
      xenograft model. These results suggested that a dUTPase inhibitor may have
      potential for clinical usage.

PMID- 22607123
TI  - Theoretical analysis of the two-electron transfer reaction and experimental
      studies with surface-confined cytochrome c peroxidase using large-amplitude
      Fourier transformed AC voltammetry.
AB  - A detailed analysis of the cooperative two-electron transfer of surface-confined
      cytochrome c peroxidase (CcP) in contact with pH 6.0 phosphate buffer solution
      has been undertaken. This investigation is prompted by the prospect of achieving
      a richer understanding of this biologically important system via the employment
      of kinetically sensitive, but background devoid, higher harmonic components
      available in the large-amplitude Fourier transform ac voltammetric method. Data
      obtained from the conventional dc cyclic voltammetric method are also provided
      for comparison. Theoretical considerations based on both ac and dc approaches are
      presented for cases where reversible or quasi-reversible cooperative two-electron
      transfer involves variation in the separation of their reversible potentials,
      including potential inversion (as described previously for solution phase
      studies), and reversibility of the electrode processes. Comparison is also made
      with respect to the case of a simultaneous two-electron transfer process that is
      unlikely to occur in the physiological situation. Theoretical analysis confirms
      that the ac higher harmonic components provide greater sensitivity to the various
      mechanistic nuances that can arise in two-electron surface-confined processes.
      Experimentally, the ac perturbation with amplitude and frequency of 200 mV and
      3.88 Hz, respectively, was employed to detect the electron transfer when CcP is
      confined to the surface of a graphite electrode. Simulations based on cooperative
      two-electron transfer with the employment of reversible potentials of 0.745 +/-
      0.010 V, heterogeneous electron transfer rate constants of between 3 and 10 s(-1)
      and charge transfer coefficients of 0.5 for both processes fitted experimental
      data for the fifth to eighth ac harmonics. Imperfections in theory-experiment
      comparison are consistent with kinetic and thermodynamic dispersion and other
      nonidealities not included in the theory used to model the voltammetry of surface
      confined CcP.

PMID- 22607124
TI  - Transcatheter closure of patent foramen ovale for hypoxemia during left
      ventricular assist device support.
AB  - The diagnosis of a patent foramen ovale (PFO) is a dynamic process and it is
      based on the detection of blood shunting at the atrial level. Only under abnormal
      physiologic conditions, such as with a left ventricular assist device (LVAD),
      when right atrial pressure (RAP) exceeds left atrial pressure (LAP) the PFO may
      cause hypoxemia due to a right-to-left shunt. We report the closure of a PFO
      using a transcatheter approach in a patient on LVAD support.

PMID- 22607126
TI  - The relationship between orphanhood and child fostering in sub-Saharan Africa,
      1990s-2000s.
AB  - In countries most afflicted by HIV/AIDS in sub-Saharan Africa, orphanhood has
      increased dramatically, but the potential consequences of the increase have been
      mitigated by the ability of households to absorb orphans. This paper examines
      what the rising levels of orphanhood mean for the common practice of non-orphan
      child fostering in regions of high and low HIV prevalence in sub-Saharan Africa,
      which has a long history of child fostering. Using Demographic and Health Survey
      data from 135 regions within 14 sub-Saharan countries that undertake HIV testing
      and have had at least two surveys, we examine changes in fostering patterns. In
      most regions, we find a more accommodating relationship between orphan and non
      orphan fostering: communities are able to absorb the demand for both orphans and
      non-orphans. Where HIV prevalence exceeds 10 per cent there is some evidence that
      the need to care for orphans is beginning to reduce opportunities for non-orphan
      fostering.

PMID- 22607125
TI  - Estimation of plasma apolipoprotein B concentration using routinely measured
      lipid biochemical tests in apparently healthy Asian adults.
AB  - BACKGROUND: Increased low-density lipoprotein cholesterol (LDL) concentration is
      associated with increased risk of coronary heart disease (CHD) but a substantial
      risk of cardiovascular disease often remains after LDL concentrations have been
      treated to target. Apolipoprotein B (apo B) is the major apolipoprotein contained
      within atherogenic lipoproteins such as LDL, and apo B is a more reliable
      indicator of cardiovascular risk than LDL concentration. AIM AND METHODS: Our aim
      was to develop a formula for calculating apo B using lipid biochemistry
      measurements that are commonly available in clinical practice. We examined the
      clinical and laboratory data from 73,047 Koreans who underwent a medical health
      check that included apolipoprotein B concentration. The study sample was randomly
      divided into a training set for prediction model building and a validation set of
      equal size. Multivariable linear regression analysis was used to develop a
      prediction model equation for estimating apo B and to validate the developed
      model. RESULTS: The best results for estimating apo B were derived from an
      equation utilising LDL and triglyceride (TG) concentrations [ApoB = -33.12 +
      0.675*LDL + 11.95*ln(tg)]. This equation predicted the apo B result with a
      concordance correlation coefficient (CCC and 95%CIs) = 0.936 (0.935,0.937)).
      CONCLUSION: Our equation for predicting apo B concentrations from routine
      analytical lipid biochemistry provides a simple method for obtaining precise
      information about an important cardiovascular risk marker.

PMID- 22607127
TI  - Autism and esophageal achalasia in childhood: a possible correlation? Report on
      three cases.
AB  - Chronic gastrointestinal symptoms are commonly reported in autistic patients.
      Dysphagia is often present, and it is generally related to behavioral eating
      disorders. The association between autism and esophageal achalasia has not been
      described in literature yet. We report our experience with three cases of
      autistic children we recently treated for esophageal achalasia. In the first case
      (a 14-year-old male), achalasia was diagnosed with barium swallow and esophageal
      manometry and was successfully treated with three pneumatic endoscopic
      dilatations (follow-up: 3 years). In the second case (a 12-year-old female),
      achalasia was diagnosed with barium swallow and esophageal manometry and was
      treated with Heller myotomy after two unsuccessful pneumatic endoscopic attempts
      (follow-up: 3 months). In the last case, a 15-year-old male underwent barium
      swallow and endoscopy that confirmed achalasia. He was treated with Heller
      myotomy, and he is asymptomatic at a 6-month follow-up. To our knowledge, this is
      the first report of a possible association between autism and esophageal
      achalasia. Because of the rarity of both diseases, their association in the same
      patient is unlikely to be casual even if speculation on their common etiology is
      impossible at present. This finding needs further confirmation, but it is
      sufficient, in our opinion, to indicate proper evaluation with barium swallow
      and/or manometry in any autistic children with eating difficulty.

PMID- 22607129
TI  - How can Faecalibacterium prausnitzii employ riboflavin for extracellular electron
      transfer?
AB  - Faecalibacterium prausnitzii is one of the most abundant commensal microbes in
      the human gut. It is an important supplier of butyrate to the colonic epithelium,
      and low numbers of faecalibacteria have been associated with severe inflammatory
      bowel disease. Previous studies revealed that F. prausnitzii shuttles electrons
      extracellularly to oxygen in systems containing flavins and thiols. Since this
      electron shuttling to oxygen strongly stimulates growth, the present studies were
      aimed at elucidating the role of riboflavin as an extracellular electronophore of
      F. prausnitzii. We show that F. prausnitzii can use riboflavin as a mediator for
      extracellular electron transfer (EET) to the anode of microbial fuel cell
      systems. However, this bacterium relies on exogenous riboflavin, since it does
      not secrete this compound as shown by the analysis of a spent growth medium using
      cyclic voltammetry (CV). Importantly, CV showed that riboflavin can undergo fully
      reversible redox cycling under physiologically relevant conditions. Lastly,
      riboflavin is shown to mediate the electrochemical oxidation of the main
      bacterial reducing equivalent NADH. Based on our present observations, we
      hypothesize that riboflavin is of major importance as a redox mediator for
      bacterial EET and growth in the human gut.

PMID- 22607128
TI  - Synthesis of 5-fluoro- and 5-hydroxymethanoprolines via lithiation of N-BOC
      methanopyrrolidines. Constrained Cgamma-exo and Cgamma-endo Flp and Hyp conformer
      mimics.
AB  - Proline derivatives with a C(gamma)-exo pucker typically display a high amide
      bond trans/cis (K(T/C)) ratio. This pucker enhances n->pi* overlap of the amide
      oxygen and ester carbonyl carbon, which favors a trans amide bond. If there were
      no difference in n->pi* interaction between the ring puckers, then the
      correlation between ring pucker and K(T/C) might be broken. To explore this
      possibility, proline conformations were constrained using a methylene bridge. We
      synthesized discrete gauche and anti 5-fluoro- and 5-hydroxy-N
      acetylmethanoproline methyl esters from 3-syn and 3-anti fluoro- and
      hydroxymethanopyrrolidines using directed alpha-metalation to introduce the alpha
      ester group. NBO calculations reveal minimal n->pi* orbital interactions, so
      contributions from other forces might be of greater importance in determining
      K(T/C) for the methanoprolines. Consistent with this hypothesis, greater trans
      amide preferences were found in CDCl(3) for anti isomers en-MetFlp and en-MetHyp
      (72-78% trans) than for the syn stereoisomers ex-MetFlp and ex-MetHyp (54-67%
      trans). These, and other, K(T/C) results that we report here indicate how
      substituents on proline analogues can affect amide preferences by pathways other
      than ring puckering and n->pi* overlap and suggest that caution should be
      exercised in assigning enhanced pyrrolidine C(gamma)-exo ring puckering based
      solely on enhanced trans amide preference.

PMID- 22607130
TI  - Design and evaluation of a self-microemulsifying drug delivery system for
      apigenin.
AB  - Objective of this study was to prepare, characterize and evaluate a self
      microemulsifying drug delivery system (SMEDDS) with the aim to improve the
      solubility and dissolution of apigenin. Ternary phase diagrams were constructed
      in order to obtain the most efficient self-emulsification region, and the
      formulation of apigenin loaded SMEDDS was optimized by a simplex lattice
      experiment design. The optimal formulation of SMEDDS obtained was comprised of
      60% Cremophor((r))EL, 30% Transcutol((r))HP and 10% CapryolTM 90. The equilibrium
      solubility of apigenin in SMEDDS was about 15 mg/g, and it could increase the
      solubility of apigenin in water for about 7500 folds. Apigenin loaded SMEDDS
      could turn into microemulsion when diluted with distilled water and the droplets
      were spherical under transmission electron microscope (TEM), the average particle
      size was 17.1 nm and zeta potential -5.18 mV. In vitro dissolution studies showed
      about 95% of apigenin was released within 10 min. All of the results showed that
      SMEDDS could enhance the solubility and dissolution of apigenin, and would be a
      potential carrier to improve the oral absorption of apigenin, a poorly water
      soluble drug.

PMID- 22607131
TI  - Rapid transformation of protein-caged nanomaterials into microbubbles as bimodal
      imaging agents.
AB  - We present a general method for converting colloidal nanomaterials into
      microbubbles as ultrasound contrast agents. Protein-caged nanomaterials, made
      either by self-assembled nanoparticles' protein corona or by fluorescent gold
      nanoclusters, can be rapidly transformed into microbubbles via a sonochemical
      route, which promote disulfide cross-linking of cysteine residues between protein
      caged nanomaterials and free albumin during acoustic cavitation. The proposed
      methods yielded microbubbles with multiple functions by adjusting the original
      nanoparticle/protein mixture. We also showed a new dual-modal imaging agent of
      fluorescent gold microbubbles in vitro and in vivo, which can hold many potential
      applications in medical diagnostics and therapy.

PMID- 22607132
TI  - Sibutramine-induced mania as the first manifestation of bipolar disorder.
AB  - BACKGROUND: Sibutramine, used in obesity treatment, has been associated with many
      neuropsychiatric side effects including hypomanic and manic episodes.
      Hypomanic/manic episodes related to sibutramine treatment were earlier reported
      in patients who had previous history of bipolar disorder, after sibutramine
      overdose, after over-the-counter product illegally containing very high dose of
      sibutramine, together with psychotic symptoms, in organic patient, or after
      interaction of sibutramine with other drugs. CASE PRESENTATION: We report the
      first case of a patient with clear manic episode, after treatment with
      recommended dose of sibutramine, without previous history of mood disorders,
      organic changes or drug interactions, that was followed by episode of depression.
      CONCLUSION: Minimal recommended dose of sibutramine induced manic episode that
      was the first manifestation of bipolar disorder. The manic episode, associated
      with sibutramine treatment, was induced in a person without previous history of
      mood disorders. Potential risks associated with the treatment of obesity using
      sibutramine warn physicians to be alert not only to common and cardiovascular but
      also to psychiatric adverse effects. A careful assessment of patient's mental
      state and detailed psychiatric family history should be done before sibutramine
      treatment. In patients with a family history for bipolar disorder the use of even
      minimal dose of sibutramine should be contraindicated.

PMID- 22607133
TI  - Reciprocal induction of human dermal microvascular endothelial cells and human
      mesenchymal stem cells: time-dependent profile in a co-culture system.
AB  - OBJECTIVES: Angiogenesis is closely associated with osteogenesis where reciprocal
      interactions between endothelial and osteoblast cells play an important role in
      bone regeneration. For these reasons, the aim of this work was to develop a co
      culture system to study in detail any time-dependent interactions between human
      mesenchymal stem cells (HMSC) and human dermal microvascular endothelial cells
      (HDMEC), co-cultured in a 2D system, for 35 days. MATERIALS AND METHODS: HMSC and
      HDMEC were co-cultured at a ratio of 1:4, respectively. Single-cell cultures were
      used as controls. Cell viability/proliferation was assessed using MTT, DNA
      quantification and calcein-AM assays. Cell morphology was monitored using
      confocal microscopy, and real time PCR was performed. Alkaline phosphatase
      activity and histochemical staining were evaluated. Matrix mineralization assays
      were also performed. RESULTS: Cells were able to grow in characteristic patterns
      maintaining their viability and phenotype expression throughout culture time,
      compared to HMSC and HDMEC monocultures. HMSC differentiation seemed to be
      enhanced in the co-culture conditions, since it was observed an over expression
      of osteogenesis-related genes, and of ALP activity. Furthermore, presence of
      calcium phosphate deposits was also confirmed. CONCLUSIONS: This work reports in
      detail the interactions between HMSC and HDMEC in a long-term co-culture 2D
      system. Endothelial and mesenchymal stem cells cultured in the present co-culture
      conditions ensured proliferation and phenotype differentiation of cell types,
      osteogenesis stimulation and over-expression of angiogenesis-related genes, in
      the same culture system. It is believed that the present work can lead to
      significant developments for bone tissue regeneration and cell biology studies.

PMID- 22607135
TI  - Effect of estrogen on pseudomonas mucoidy and exacerbations in cystic fibrosis.
AB  - BACKGROUND: Women with cystic fibrosis are at increased risk for mucoid
      conversion of Pseudomonas aeruginosa, which contributes to a sexual dichotomy in
      disease severity. METHODS: We evaluated the effects of estradiol and its
      metabolite estriol on P. aeruginosa in vitro and in vivo and determined the
      effect of estradiol on disease exacerbations in women with cystic fibrosis.
      RESULTS: Estradiol and estriol induced alginate production in P. aeruginosa
      strain 01 and in clinical isolates obtained from patients with and those without
      cystic fibrosis. After prolonged exposure to estradiol, P. aeruginosa adopted
      early mucoid morphology, whereas short-term exposure inhibited bacterial catalase
      activity and increased levels of hydrogen peroxide, which is potentially damaging
      to DNA. Consequently, a frameshift mutation was identified in mucA, a key
      regulator of alginate biosynthesis in P. aeruginosa. In vivo levels of estradiol
      correlated with infective exacerbations in women with cystic fibrosis, with the
      majority occurring during the follicular phase (P<0.05). A review of the Cystic
      Fibrosis Registry of Ireland revealed that the use of oral contraceptives was
      associated with a decreased need for antibiotics. Predominantly nonmucoid P.
      aeruginosa was isolated from sputum during exacerbations in the luteal phase (low
      estradiol). Increased proportions of mucoid bacteria were isolated during
      exacerbations occurring in the follicular phase (high estradiol), with a variable
      P. aeruginosa phenotype evident in vivo during the course of the menstrual cycle
      corresponding to fluctuating estradiol levels. CONCLUSIONS: Estradiol and estriol
      induced mucoid conversion of P. aeruginosa in women with cystic fibrosis through
      a mutation of mucA in vitro and were associated with selectivity for mucoid
      isolation, increased exacerbations, and mucoid conversion in vivo. (Funded by the
      Molecular Medicine Ireland Clinician-Scientist Fellowship Programme.).

PMID- 22607136
TI  - Involvement of CD11b integrin in the alteration of metabolic factors after
      phorbol ester stimulation of human myeloid leukemia cells.
AB  - Previous work has demonstrated that phorbol ester (TPA)-induced adherence of
      human U937 myeloid leukemia cells can be blocked upon down-modulation of the
      beta2-integrin CD11b after stable transfection of U937 cells with a pMTH1 vector
      containing the CD11b gene in antisense orientation (asCD11b-U937) [Otte et al.,
      (2011)]. In the present study, alterations in metabolism-associated factors,
      particularly intra- and extracellular proteases were investigated. A measurement
      of telomerase activity in the leukemic cells revealed continuously decreasing
      telomere adducts within 72 h of TPA treatment in pMTH1-U937 cells. In contrast,
      telomerase activity sustained in asCD11b-U937 upon TPA-induced differentiation.
      Flow cytometric analysis confirmed unchanged CD11b levels in TPA-induced asCD11b
      U937 in contrast to elevated levels in pMTH1-U937 whereby the expression of other
      beta2-integrins including CD11a, CD11c and CD18 was increased in both populations
      after TPA treatment. Moreover, adherent pMTH1-U937 demonstrated the expression of
      monocytic differentiation markers including F4-80 and CD14 and an increased MIP
      1alpha production which remained at low or undetectable in TPA-induced asCD11b
      U937. These effects indicated an altered response of the different cell
      populations to the TPA-induced differentiation process. Indeed, Western blot
      analysis revealed differences in the expression levels of intracellular metabolic
      factors including MnSOD and p97/VCP and after measurement of 20 S proteasomal
      proteolytic activity. In addition, increased levels of extracellular metabolic
      factors including the matrix metalloproteinases MMP-1, MMP-7 and MMP-9 were
      observed in pMTH1-U937 cells in contrast to unaltered levels in asCD11b-U937
      cells.

PMID- 22607134
TI  - Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis.
AB  - BACKGROUND: A combination of prednisone, azathioprine, and N-acetylcysteine (NAC)
      has been widely used as a treatment for idiopathic pulmonary fibrosis. The safety
      and efficacy of this three-drug regimen is unknown. METHODS: In this randomized,
      double-blind, placebo-controlled trial, we assigned patients with idiopathic
      pulmonary fibrosis who had mild-to-moderate lung-function impairment to one of
      three groups -- receiving a combination of prednisone, azathioprine, and NAC
      (combination therapy), NAC alone, or placebo -- in a 1:1:1 ratio. The primary
      outcome was the change in longitudinal measurements of forced vital capacity
      during a 60-week treatment period. RESULTS: When approximately 50% of data had
      been collected (with 77 patients in the combination-therapy group and 78 in the
      placebo group), a planned interim analysis revealed that patients in the
      combination-therapy group, as compared with the placebo group, had an increased
      rate of death (8 vs. 1, P=0.01) and hospitalization (23 vs. 7, P<0.001). These
      observations, coupled with no evidence of physiological or clinical benefit for
      combination therapy, prompted the independent data and safety monitoring board to
      recommend termination of the combination-therapy group at a mean follow-up of 32
      weeks. Data from the ongoing comparison of the NAC-only group and the placebo
      group are not reported here. CONCLUSIONS: Increased risks of death and
      hospitalization were observed in patients with idiopathic pulmonary fibrosis who
      were treated with a combination of prednisone, azathioprine, and NAC, as compared
      with placebo. These findings provide evidence against the use of this combination
      in such patients. (Funded by the National Heart, Lung, and Blood Institute and
      the Cowlin Family Fund; ClinicalTrials.gov number, NCT00650091.).

PMID- 22607137
TI  - Inflammation-induced changes in BK(Ca) currents in cutaneous dorsal root ganglion
      neurons from the adult rat.
AB  - BACKGROUND: Inflammation-induced sensitization of primary afferents is associated
      with a decrease in K(+) current. However, the type of K(+) current and basis for
      the decrease varies as a function of target of innervation. Because glabrous skin
      of the rat hindpaw is used often to assess changes in nociception in models of
      persistent pain, the purpose of the present study was to determine the type and
      extent to which K(+) currents contribute to the inflammation-induced
      sensitization of cutaneous afferents. Acutely dissociated retrogradely labeled
      cutaneous dorsal root ganglion neurons from naive and inflamed (3 days post
      complete Freund's adjuvant injection) rats were studied with whole cell and
      perforated patch techniques. RESULTS: Inflammation-induced sensitization of small
      diameter cutaneous neurons was associated with an increase in action potential
      duration and rate of decay of the afterhyperpolarization. However, no changes in
      voltage-gated K(+) currents were detected. In contrast, Ca(2+) modulated
      iberiotoxin sensitive and paxilline sensitive K(+) (BK(Ca)) currents were
      significantly smaller in small diameter IB4+ neurons. This decrease in current
      was not associated with a detectable change in total protein levels of the BK(Ca)
      channel alpha or beta subunits. Single cell PCR analysis revealed a significant
      change in the pattern of expression of alpha subunit splice variants and beta
      subunits that were consistent, at least in part, with inflammation-induced
      changes in the biophysical properties of BK(Ca) currents in cutaneous neurons.
      CONCLUSIONS: Results of this study provide additional support for the conclusion
      that it may be possible, if not necessary to selectively treat pain arising from
      specific body regions. Because a decrease in BK(Ca) current appears to contribute
      to the inflammation-induced sensitization of cutaneous afferents, BK(Ca) channel
      openers may be effective for the treatment of inflammatory pain.

PMID- 22607139
TI  - Choline analogues in malaria chemotherapy.
AB  - Emerging resistance against well-established anti-malaria drugs warrants the
      introduction of new therapeutic agents with original mechanisms of action.
      Inhibition of membrane-based phospholipid biosynthesis, which is crucial for the
      parasite, has thus been proposed as a novel and promising therapeutic strategy.
      This review compiles literature concerning the design and study of choline
      analogues and related cation derivatives as potential anti-malarials. It covers
      advances achieved over the last two decades and describes: the concept
      validation, the design and selection of a clinical candidate (Albitiazolium),
      back-up derivatives while also providing insight into the development of prodrug
      approaches.

PMID- 22607140
TI  - Towards histone deacetylase inhibitors as new antimalarial drugs.
AB  - Histone deacetylases (HDACs) are important enzymes that effect post-translational
      modifications of proteins by altering the acetylation state of lysine residues.
      HDACs control epigenetic changes that trigger cell transformation and
      proliferation of transformed cells associated with many diseases. These enzymes
      are validated drug targets for some types of cancer and are promising therapeutic
      targets for a range of other diseases, including malaria. Annually, there are
      ~500 million clinical cases of malaria and ~0.8-1.2 million deaths. There is no
      licensed vaccine for preventing malaria, and parasites that cause malaria are
      becoming resistant to current drugs, necessitating the search for new therapies.
      HDAC inhibitors are emerging as a promising new class of antimalarial drugs with
      potent and selective action against Plasmodium parasites in vitro. Recent studies
      on the effects of HDAC inhibitors on the growth and development of P. falciparum
      have provided important new information on transcriptional regulation in malaria
      parasites and have validated the potential of this class of inhibitors for
      malaria therapy. To realise effective HDAC inhibitors for clinical trials, next
      generation inhibitors must not inhibit other human HDACs or proteins required for
      normal human physiology, be highly selective in killing parasites in vivo without
      killing normal host cells, and have improved bioavailability and pharmacokinetic
      profiles. This review summarizes current knowledge about malaria parasite HDACs
      and HDAC inhibitors with antimalarial properties, and provides insights for their
      development into new drugs for treatment of malaria.

PMID- 22607142
TI  - The apicoplast: a key target to cure malaria.
AB  - Malaria is one of the major global health problems. About 500 million humans are
      infected each year, and 1 million, mostly African children, die from malaria
      annually. No vaccine is yet in sight, and those drugs that have previously served
      us well are now losing ground against the disease as parasites become resistant
      to our best compounds. The need for development of new antimalarials is now more
      urgent than ever. An exciting avenue for development of new drugs emerged
      recently when it was discovered that the malaria parasites have a previously
      unrecognized evolutionary history aligned to plants. These parasites contain a
      subcellular compartment--the apicoplast--which is homologous to the chloroplast
      of plants and algae, in which photosynthesis occurs. The malaria chloroplast
      (apicoplast) has lost photosynthesis but it retains many chloroplast pathways,
      which are otherwise unique to plants. These pathways obviously do not exist in
      the human host and there has been considerable excitement about using the
      apicoplast as a parasite-specific Achilles' Heel. We propose to review the
      current state of development of novel compounds directed against this emerging
      target of malaria parasites with emphasis on the chemistry.

PMID- 22607141
TI  - Lipoic acid metabolism of Plasmodium--a suitable drug target.
AB  - alpha-Lipoic acid (6,8-thioctic acid; LA) is a vital co-factor of alpha-ketoacid
      dehydrogenase complexes and the glycine cleavage system. In recent years it was
      shown that biosynthesis and salvage of LA in Plasmodium are necessary for the
      parasites to complete their complex life cycle. LA salvage requires two lipoic
      acid protein ligases (LplA1 and LplA2). LplA1 is confined to the mitochondrion
      while LplA2 is located in both the mitochondrion and the apicoplast. LplA1
      exclusively uses salvaged LA and lipoylates alpha-ketoglutarate dehydrogenase,
      branched chain alpha-ketoacid dehydrogenase and the H-protein of the glycine
      cleavage system. LplA2 cannot compensate for the loss of LplA1 function during
      blood stage development suggesting a specific function for LplA2 that has yet to
      be elucidated. LA salvage is essential for the intra-erythrocytic and liver stage
      development of Plasmodium and thus offers great potential for future drug or
      vaccine development. LA biosynthesis, comprising octanoyl-acyl carrier protein
      (ACP) : protein N-octanoyltransferase (LipB) and lipoate synthase (LipA), is
      exclusively found in the apicoplast of Plasmodium where it generates LA de novo
      from octanoyl-ACP, provided by the type II fatty acid biosynthesis (FAS II)
      pathway also present in the organelle. LA is the co-factor of the
      acetyltransferase subunit of the apicoplast located pyruvate dehydrogenase (PDH),
      which generates acetyl-CoA, feeding into FAS II. LA biosynthesis is not vital for
      intra-erythrocytic development of Plasmodium, but the deletion of several genes
      encoding components of FAS II or PDH was detrimental for liver stage development
      of the parasites indirectly suggesting that the same applies to LA biosynthesis.
      These data provide strong evidence that LA salvage and biosynthesis are vital for
      different stages of Plasmodium development and offer potential for drug and
      vaccine design against malaria.

PMID- 22607143
TI  - Novel drug targets in malaria parasite with potential to yield antimalarial drugs
      with long useful therapeutic lives.
AB  - The status of chemotherapy as the main strategy in malaria control is rapidly
      being eroded by development of drug resistant Plasmodia, causing malaria to be
      dubbed a "re-emerging disease". To counter this misfortune, there is an urgent
      need to develop novel antimalarial drugs capable of delaying resistance, or
      circumventing it altogether. Mode of action of antimalarial drugs, inter alia,
      has a bearing on their useful therapeutic lives (UTLs), with single target drugs
      having short UTLs compared with drugs which possess pleiotropic action.
      Quinolines and artemisinins are the two classes of drugs with pleiotropic action
      and subsequently long UTLs. All other antimalarials are single-target drugs, and
      have been rendered ineffective within 1 to 5 years of their introduction for
      clinical use. This strongly underlines the need for development of new
      antimalarial therapies possessing long UTLs. The present review explores novel
      drug targets within the malaria parasite that may be exploited in the search for
      novel drugs that possess long and UTLs.

PMID- 22607144
TI  - Inhibition of protein-protein interactions in Plasmodium falciparum: future drug
      targets.
AB  - The rapid development by malaria parasites of resistance to almost all the
      chemotherapeutic agents so far used for their control means that constant efforts
      to develop new drugs are necessary. In this review, we propose that the
      exploration of protein-protein interactions as a new strategy to identify
      antimalarial drug targets is an attractive and a promising area of research.
      Nevertheless, one of the most important criteria is that the targeted gene should
      encode an essential protein within a complex that is able to affect parasite
      survival. Recently, our research on the biology of Plasmodium falciparum allowed
      us to identify the interaction of Protein Phosphatase type 1 and actin with two
      essential partners, PfLRR1 and PfLRR7 respectively, both of which belong to the
      Leucine Rich Repeat (LRR) protein family. LRR-containing proteins are composed of
      several consensus LRR motifs LXLXXNXL (where X is any amino acid) that provide
      sites for the assembly of protein interactions. The LRR combines structural
      versatility, adaptability and more importantly a high degree of interaction
      specificity. In addition, it has been shown that a single mutation in a
      particular LRR motif abolishes the protein-protein interaction and contributes to
      the expression of severe pathology in humans. This clearly infers that blocking
      the interaction related to 'hot spots' of LRR motifs can be considered as good
      targets to block parasite growth and development. Thus, the inhibition of protein
      protein interactions by peptides, peptidomimetics or small-molecule inhibitors
      that interfere with binding domains can contribute to defining new potential drug
      targets.

PMID- 22607145
TI  - Antimalarials in the treatment of schistosomiasis.
AB  - With just one drug used for individual patient management and community-based
      morbidity control, the treatment, control, and eventual elimination of
      schistosomiasis is vulnerable should resistance to praziquantel emerge and
      spread. The discovery and development of novel chemical entities that exhibit
      antischistosomal properties, and the repurposing of existing drugs for
      schistosomiasis is thus of central importance as long as praziquantel remains
      effective. Here, we discuss the public health relevance of schistosomiasis, which
      is currently considered a neglected tropical disease. We recapitulate the past
      and current drug armamentarium against schistosomiasis, including shortcomings
      and a target product profile of an antischistosomal drug. The central piece of
      our review is the discovery of the antischistosomal properties of various
      antimalarial drugs, notably the artemisinins, synthetic trioxolanes, and
      mefloquine. We summarize findings from preclinical investigations and experiences
      made thus far from clinical studies. We conclude that a closer collaboration
      between the malaria and schistosomiasis communities might facilitate the
      discovery and development of novel antischistosomal drugs, and will foster
      monitoring and evaluation of the ancillary benefits of antimalarial prophylaxis
      and treatment against schistosomiasis.

PMID- 22607147
TI  - Targeting schistosome histone modifying enzymes for drug development.
AB  - The histone modifying enzymes (HME) represent particularly promising targets for
      the development of alternatives to praziquantel, the only currently available
      drug to combat schistosomiasis. The inhibition of these enzymes frequently
      arrests the cell cycle or induces apoptosis in cancer cells, but not in normal
      cells and numerous HME inhibitors are under investigation as potential anticancer
      agents. The recent resolution of the genome sequences of Schistosoma mansoni and
      Schistosoma japonicum has allowed us to identify all the schistosome genes
      encoding histone acetyltransferases, deacetylases, methyltransferases and
      demethylases. We have chosen a strategy using phylogenetic screening with
      inhibitors of HME classes, screening of individual HME targets by both high
      throughput and reasoned (in silico docking using resolved crystal structures)
      approaches in a project funded by the European Community, named SEtTReND
      (Schistosome Epigenetics: Targets, Regulation, New Drugs). The initial focus is
      on the class I histone deacetylase (HDAC) 8 since the comparison of the catalytic
      site of the schistosome and human enzymes shows crucial differences, rendering
      possible the development of inhibitors specific for SmHDAC8. However, phenotypic
      screening shows that inhibitors of all HME classes tested were able to induce
      apoptosis and death in parasites in vitro, indicating that other enzymes may
      prove to be viable targets.

PMID- 22607146
TI  - A physico-biochemical study on potential redox-cyclers as antimalarial and anti
      schistosomal drugs.
AB  - The role of redox enzymes in establishing a microenvironment for parasite
      development is well characterized. Mimicking human glucose-6-phosphate
      dehydrogenase and glutathione reductase (GR) deficiencies by redox-cycling
      compounds thus represents a challenge to the design of new preclinical
      antiparasitic drug candidates. Schistosomes and malarial parasites feed on
      hemoglobin. Heme, the toxic prosthetic group of the protein, is not digested and
      represents a challenge to the redox metabolism of the parasites. Here, we report
      on old and new redox-cycling compounds--whose antiparasitic activities are
      related to their interference with (met)hemoglobin degradation and hematin
      crystallization. Three key-assays allowed probing and differentiating the
      mechanisms of drug actions. Inhibition of beta-hematin was first compared to the
      heme binding as a possible mode of action. All tested ligands interact with the
      hematin pi-pi dimer with K(D) similar to those measured for the major
      antiparasitic drugs. No correlation between a high affinity for hematin and the
      capacity to prevent beta-hematin formation was however deduced. Inhibition of
      beta-hematin formation is consequently not the result of a single process but
      results from redox processes following electron transfers from the drugs to
      iron(III)-containing targets. The third experiment highlighted that several redox
      active compounds (in their reduced forms) are able to efficiently reduce
      methemoglobin to hemoglobin in a GR/NADPH-coupled assay. A correlation between
      methemoglobin reduction and inhibition of beta-hematin was shown, demonstrating
      that both processes are closely related. The ability of our redox-cyclers to
      trigger methemoglobin reduction therefore constitutes a critical step to
      understand the mechanism of action of our drug candidates.

PMID- 22607148
TI  - Protein kinases as potential targets for novel anti-schistosomal strategies.
AB  - Schistosome parasites are the causative pathogens of schistosomiasis (bilharzia),
      a disease of worldwide significance. In terms of patient numbers, schistosomiasis
      ranks second to malaria as a parasitosis affecting more than 200 million people
      of the tropics and subtropics. Since the 1970s Praziquantel (PZQ) is the drug of
      choice and nearly exclusively used for treatment. However, drug resistance is an
      increasing threat, particularly with respect to large-scale PZQ administration
      programs. Last decade's research indicated that resistance against PZQ can be
      induced under laboratory conditions, and field studies provided first indications
      for the possibility of reduced PZQ efficacy. Furthermore, clear evidence for the
      molecular armamentarium of schistosomes with multidrug transporters was found,
      one of which was responding to PZQ challenge. Also the development of a vaccine
      still represents an elusive goal, although effort and time have been invested in
      this subject. In light of these facts it is commonly accepted that new drugs are
      urgently needed. Research on signal transduction processes in Schistosoma mansoni
      has provided an unexpected and novel perspective towards this end. Molecular,
      biochemical, and physiological studies elucidating principles of schistosome
      development have demonstrated the essential role of protein kinases (PKs). In
      humans, PKs are known to be involved in cancer development. Since a variety of
      approved anticancer drugs targeting PKs exist, first studies have been performed
      to investigate whether these drugs are able to also inhibit schistosome PKs.
      Indeed, promising results have been obtained indicating the potential of PKs as
      privileged targets for new concepts in fighting schistosomes.

PMID- 22607150
TI  - Phase separation in semidilute aqueous poly(N-isopropylacrylamide) solutions.
AB  - The phase separation mechanism in semidilute aqueous poly(N-isopropylacrylamide)
      (PNIPAM) solutions is investigated with small-angle neutron scattering (SANS).
      The nature of the phase transition is probed in static SANS measurements and with
      time-dependent SANS measurements after a temperature jump. The observed critical
      exponents of the phase transition describing the temperature dependence of the
      Ornstein-Zernike amplitude and correlation length are smaller than values from
      mean-field theory. Time-dependent SANS measurements show that the specific
      surface decreases with increasing time after a temperature jump above the phase
      transition. Thus, the formation of additional hydrogen bonds in the collapsed
      state is a kinetic effect: A certain fraction of water remains as bound water in
      the system. Moreover, H-D exchange reactions observed in PNIPAM have to be taken
      into account.

PMID- 22607152
TI  - Kallikrein protease activated receptor (PAR) axis: an attractive target for drug
      development.

PMID- 22607153
TI  - Molecular insight into the counteraction of trehalose on urea-induced protein
      denaturation using molecular dynamics simulation.
AB  - Considerable experimental evidence indicates that trehalose can counteract the
      denaturing effects of urea on proteins. However, its molecular mechanism remains
      unknown due to the limitations of current experimental techniques. Herein,
      molecular dynamics simulations were performed to investigate the counteracting
      effects of trehalose against urea-induced denaturation of chymotrypsin inhibitor
      2. The simulations indicate that the protein unfolds in 8 mol/L urea, but at the
      same condition the protein retains its native structure in the ternary solution
      of 8 mol/L urea and 1 mol/L trehalose. It is confirmed that the preferential
      exclusion of trehalose from the protein surface is the origin of its
      counteracting effects. It is found that trehalose binds urea via hydrogen bonds,
      so urea molecules are also expelled from the protein surface along with the
      preferential exclusion of trehalose. The exclusion of urea from the protein
      surface leads to the alleviation of the Lennard-Jones interactions between urea
      and the hydrophobic side chains of the protein in the ternary solution. In
      contrast, the electrostatic interactions between urea and the protein change
      little in the presence of trehalose because the decrease in the electrostatic
      interactions between urea and the protein backbone is canceled by the increase in
      the electrostatic interactions between urea and the charged side chains of the
      protein. The results have provided molecular explanations for the counteraction
      of urea-induced protein denaturation by trehalose.

PMID- 22607149
TI  - The redox biology of schistosome parasites and applications for drug development.
AB  - Schistosomiasis caused by Schistosoma spp. is a serious public health concern,
      especially in sub-Saharan Africa. Praziquantel is the only drug currently
      administrated to treat this disease. However, praziquantel-resistant parasites
      have been identified in endemic areas and can be generated in the laboratory.
      Therefore, it is essential to find new therapeutics. Antioxidants are appealing
      drug targets. In order to survive in their hosts, schistosomes are challenged by
      reactive oxygen species from intrinsic and extrinsic sources. Schistosome
      antioxidant enzymes have been identified as essential proteins and novel drug
      targets and inhibition of the antioxidant response can lead to parasite death.
      Because the organization of the redox network in schistosomes is significantly
      different from that in humans, new drugs are being developed targeting
      schistosome antioxidants. In this paper the redox biology of schistosomes is
      discussed and their potential use as drug targets is reviewed. It is hoped that
      compounds targeting parasite antioxidant responses will become clinically
      relevant drugs in the near future.

PMID- 22607154
TI  - Gallium nitride nanowire based nanogenerators and light-emitting diodes.
AB  - Single-crystal n-type GaN nanowires have been grown epitaxially on a Mg-doped p
      type GaN substrate. Piezoelectric nanognerators based on GaN nanowires are
      investigated by conductive AFM, and the results showed an output power density of
      nearly 12.5 mW/m(2). Luminous LED modules based on n-GaN nanowires/p-GaN
      substrate have been fabricated. CCD images of the lighted LED and the
      corresponding electroluminescence spectra are recorded at a forward bias.
      Moreover, the GaN nanowire LED can be lighted up by the power provided by a ZnO
      nanowire based nanogenerator, demonstrating a self-powered LED using wurtzite
      structured nanomaterials.

PMID- 22607155
TI  - The role of illness perceptions in the attachment-related process of affect
      regulation.
AB  - Based on the predictions of the attachment theory and the Common Sense Model of
      illness perceptions, the current study focused on the role played by illness
      perceptions in explaining the path linking attachment orientations to negative
      affect during recovery from cardiac illness. We predicted two putative
      mechanisms: (1) illness perceptions would mediate the direct association between
      attachment-related insecurity (especially attachment anxiety) and levels of
      distress at follow-up and (2) illness perceptions would interact with attachment
      orientations (attachment avoidance in particular) in explaining patients'
      distress. The sample consisted of 111 male patients admitted to the Cardiac Care
      Unit of the Meir Medical Center, located in the central region of Israel.
      Patients completed a measure of attachment orientations during hospitalization
      (baseline). One month later, patients' illness perceptions were measured.
      Patients' depression and anxiety symptoms were measured at baseline and at the
      six-month follow-up. The associations between attachment-related anxiety and
      anxiety symptoms at follow-up were fully mediated by illness perceptions.
      Attachment-related avoidance was found to interact with illness perceptions in
      the prediction of depressive symptoms at follow-up. The findings shed light on
      the possible dynamics among personality, cognitive appraisals, and affect
      regulation efforts when coping with illness.

PMID- 22607157
TI  - Can cognitive behavioural therapy based strategies be integrated into
      physiotherapy for the prevention of chronic low back pain? A systematic review.
AB  - PURPOSE: The primary purpose was to detect randomized controlled trials
      investigating cognitive behaviour therapy-based (CBT) treatments applied in
      acute/sub-acute low back pain (LBP). The secondary purpose was to analyse the
      methodological properties of the included studies, and to identify theory-based
      treatment strategies that are applicable for physiotherapists. METHOD: A
      systematic literature search was conducted using four databases. Risk of bias of
      included studies was assessed and the methodological properties summarized. In
      addition, content and treatment theory of detected CBT-based strategies were
      systematically analysed and classified into three distinctive concepts of CBT:
      operant, cognitive and respondent treatment. Finally, applicability of treatment
      strategies in physiotherapy practice was discussed. RESULTS: Eight studies were
      included in the present systematic review. Half of the studies suffered from high
      risk of bias, and study characteristics varied in all domains of methodology,
      particularly in terms of treatment design and outcome measures. Graded activity,
      an operant treatment approach based on principles of operant conditioning, was
      identified as a CBT-based strategy with traceable theoretical justification that
      can be applied by physiotherapists. CONCLUSION: Operant conditioning can be
      integrated in ambulant physiotherapy practice and is a promising CBT-based
      strategy for the prevention of chronic LBP.

PMID- 22607156
TI  - Exome sequencing generates high quality data in non-target regions.
AB  - BACKGROUND: Exome sequencing using next-generation sequencing technologies is a
      cost efficient approach to selectively sequencing coding regions of human genome
      for detection of disease variants. A significant amount of DNA fragments from the
      capture process fall outside target regions, and sequence data for positions
      outside target regions have been mostly ignored after alignment. RESULT: We
      performed whole exome sequencing on 22 subjects using Agilent SureSelect capture
      reagent and 6 subjects using Illumina TrueSeq capture reagent. We also downloaded
      sequencing data for 6 subjects from the 1000 Genomes Project Pilot 3 study. Using
      these data, we examined the quality of SNPs detected outside target regions by
      computing consistency rate with genotypes obtained from SNP chips or the Hapmap
      database, transition-transversion (Ti/Tv) ratio, and percentage of SNPs inside
      dbSNP. For all three platforms, we obtained high-quality SNPs outside target
      regions, and some far from target regions. In our Agilent SureSelect data, we
      obtained 84,049 high-quality SNPs outside target regions compared to 65,231 SNPs
      inside target regions (a 129% increase). For our Illumina TrueSeq data, we
      obtained 222,171 high-quality SNPs outside target regions compared to 95,818 SNPs
      inside target regions (a 232% increase). For the data from the 1000 Genomes
      Project, we obtained 7,139 high-quality SNPs outside target regions compared to
      1,548 SNPs inside target regions (a 461% increase). CONCLUSIONS: These results
      demonstrate that a significant amount of high quality genotypes outside target
      regions can be obtained from exome sequencing data. These data should not be
      ignored in genetic epidemiology studies.

PMID- 22607158
TI  - Intra-aortic balloon counterpulsation in the treatment of infarction-related
      cardiogenic shock--review of the current evidence.
AB  - The European ST-elevated myocardial infarction (STEMI) guideline suggested the
      intra-aortic balloon pump (IABP) with a recommendation level I and a level of
      evidence C as an effective measure in combination with balloon angioplasty in
      patients with cardiogenic shock (CS), stent implantation, and inotropic and
      vasopressor support. Similarly, upon mechanical complication due to myocardial
      infarction (MI), the guideline suggests that in patients with a ventricular
      septal defect or in most patients with acute mitral regurgitation, preoperative
      IABP implantation is indicated for circulatory support. The American College of
      Cardiology/American Heart Association STEMI guideline recommends the use of the
      IABP with a recommendation level I and a level of evidence B if CS does not
      respond rapidly to pharmacological treatment. The guideline notes that the IABP
      is a stabilizing measure for angiography and early revascularization. Even in MI
      complications, the use of preoperative IABP is recommended before surgery. Within
      this overview, we summarize the current evidence on IABP use in patients with CS
      complicated by MI. From our Cochrane data analysis, we conclude that in CS due to
      acute MI (AMI) treated with adjuvant systemic fibrinolysis, the IABP should be
      implanted. In patients with CS following AMI, treated with primary percutaneous
      coronary intervention (PCI), the IABP can be implanted, although data are not
      distinctive (i.e., indicating positive and negative effects). In the future,
      randomized controlled trials are needed to determine the use of IABP in CS
      patients treated with PCI. When patients with CS are transferred to a PCI center
      with or without thrombolysis, patients should receive mechanical support with an
      IABP. To treat mechanical MI complications-in particular ventricular septal
      defect-patients should be treated with an IABP to stabilize their hemodynamic
      situation prior to cardiac surgery. Similar recommendations are given in the
      German Austrian guidelines on treatment of infarction-related CS patients
      (http://www.awmf.org/leitlinien/detail/ll/019-013.html).

PMID- 22607159
TI  - Malignancy through cooperation: an evolutionary game theory approach.
AB  - OBJECTIVE: Traditional cancer initiation theory propounds evolution of a
      monoclonal population of fully transformed tumour cells to form a malignant
      tumour. Cooperation between surrounding stroma and the tumour also often leads to
      malignancy. This cooperation may exist as a result of sharing of growth signals
      or growth factors secreted by stromal cells, which can cause those with
      proliferative phenotypes to switch to motile phenotypes. Mathematical models of
      sharing of growth factors between cancer stem cells and stromal cells can allow
      for deeper understanding of tumourigenesis through cooperation. The study
      presented here describes a novel evolutionary game theoretical approach to
      investigate emergence of malignancy through interactions among cells of three
      different phenotypes, one of which produces growth factors. MATERIALS AND
      METHODS: Three different scenarios have been considered, and types of behaviour
      of the three phenotypes during interactions, have been modelled in terms of cost
      and benefit variables. Phenotypic compositions of such a tumour at equilibrium
      have been analysed, and evolution of the population, with respect to time, has
      been investigated. RESULTS: Results suggest the role of cooperation in forming a
      malignant tumour and show, in all three cases, that emergence of triple
      polymorphism, two-strategy polymorphism, and fixation of one phenotype, were
      possible at equilibrium. The models also suggest that under certain conditions,
      one phenotype may be completely eliminated from the population, thus leading to
      new possibilities for potential treatments. CONCLUSIONS: This study explains some
      current experimental findings from a theoretical viewpoint, and may provide new
      approaches for future research in oncology.

PMID- 22607161
TI  - Prognosis of immediately loaded implants and their restorations: a systematic
      literature review.
AB  - Immediate loading of oral implants has become popular because of the increasing
      demands of a shortened treatment time. This literature review evaluates the
      prognosis of immediately loaded implants and their restorations with immediate or
      delayed implant placement. Special attention was given to the impact of type of
      jaw, bone quality, implant length, time of implant placement and type of
      restoration. An electronic (PubMed) and a manual search in relevant journals were
      conducted until February 2012. Only publications in English, in peer-reviewed
      journals, were considered. Nine studies met the inclusion criteria: five studies
      dealt with fixed restorations, two studies with removable rehabilitation of
      edentulous jaws and two studies dealt with partially edentulous patients. Implant
      survival rates ranged from 95.8% to 100%, implant success rates in the treatment
      for the mandible from 79% to 100% and restoration survival rates for both jaws
      from 96.4% to 100%. Within the limits of this review, appropriate patient
      selection, primary implant stability, splinting of implants and the expertise of
      surgeons seem to be important for the prognosis of immediately loaded implants
      and their restorations. Good bone quality and use of long implants appear to play
      a role. However, careful interpretation is required because conclusions are based
      on articles with low level of evidence. While immediate loading of oral implants
      in the mandible shows encouraging and predictable results, further multicenter
      randomised controlled clinical trials with sufficient statistical power are
      needed to examine (i) the outcome of immediately loaded implants in the maxilla
      and (ii) the outcome of immediate loading of immediately placed implants.

PMID- 22607162
TI  - 8-AminoBODIPYs: cyanines or hemicyanines? The effect of the coplanarity of the
      amino group on their optical properties.
AB  - The role of the amino group twisting ability in the BODIPY photophysics for
      nonsterically hindered and constrained molecular structures was studied. When a
      coplanar disposition of the amino and the BODIPY core is feasible, a hemicyanine
      like delocalized pi-system gives rise to novel blue and efficient BODIPY laser
      dyes. The key role of such rotamer is confirmed by newly synthesized derivatives
      where the amino and the BODIPY core are electronically decoupled by steric
      repulsions.

PMID- 22607160
TI  - Let's prevent diabetes: study protocol for a cluster randomised controlled trial
      of an educational intervention in a multi-ethnic UK population with screen
      detected impaired glucose regulation.
AB  - BACKGROUND: The prevention of type 2 diabetes is a globally recognised health
      care priority, but there is a lack of rigorous research investigating optimal
      methods of translating diabetes prevention programmes, based on the promotion of
      a healthy lifestyle, into routine primary care. The aim of the study is to
      establish whether a pragmatic structured education programme targeting lifestyle
      and behaviour change in conjunction with motivational maintenance via the
      telephone can reduce the incidence of type 2 diabetes in people with impaired
      glucose regulation (a composite of impaired glucose tolerance and/or impaired
      fasting glucose) identified through a validated risk score screening programme in
      primary care. DESIGN: Cluster randomised controlled trial undertaken at the level
      of primary care practices. Follow-up will be conducted at 12, 24 and 36 months.
      The primary outcome is the incidence of type 2 diabetes. Secondary outcomes
      include changes in HbA1c, blood glucose levels, cardiovascular risk, the presence
      of the Metabolic Syndrome and the cost-effectiveness of the intervention.
      METHODS: The study consists of screening and intervention phases within 44
      general practices coordinated from a single academic research centre. Those at
      high risk of impaired glucose regulation or type 2 diabetes are identified using
      a risk score and invited for screening using a 75 g-oral glucose tolerance test.
      Those with screen detected impaired glucose regulation will be invited to take
      part in the trial. Practices will be randomised to standard care or the intensive
      arm. Participants from intensive arm practices will receive a structured
      education programme with motivational maintenance via the telephone and annual
      refresher sessions. The study will run from 2009-2014. DISCUSSION: This study
      will provide new evidence surrounding the long-term effectiveness of a diabetes
      prevention programme conducted within routine primary care in the United Kingdom.
      TRIAL REGISTRATION: Clinicaltrials.gov NCT00677937.

PMID- 22607163
TI  - A perplexing esophagus.

PMID- 22607164
TI  - Preconditioning induces tolerance by suppressing glutamate release in neuron
      culture ischemia models.
AB  - This study determined how preconditioned neurons responded to oxygen-glucose
      deprivation (OGD) to result in neuroprotection instead of neurotoxicity. Neurons
      preconditioned using chronically elevated synaptic activity displayed suppressed
      elevations in extracellular glutamate ([glutamateex ]) and intracellular Ca(2+)
      (Ca(2+) in ) during OGD. The glutamate uptake inhibitor TBOA induced
      neurotoxicity, but at a longer OGD duration for preconditioned cultures,
      suggestive of delayed up-regulation of transporter activity relative to non
      preconditioned cultures. This delay was attributed to a critically attenuated
      release of glutamate, based on tolerance observed against insults mimicking key
      neurotoxic signaling during OGD (OGD-mimetics). Specifically, in the presence of
      TBOA, preconditioned neurons displayed potent protection to the OGD-mimetics:
      ouabain (a Na(+) /K(+) ATPase inhibitor), high 55 mM KCl extracellular buffer
      (plasma membrane depolarization), veratridine (a Na(+) ionophore), and paraquat
      (intracellular superoxide producer), which correlated with suppressed
      [glutamateex ] elevations in the former two insults. Tolerance by preconditioning
      was reversed by manipulations that increased [glutamateex ], such as by exposure
      to TBOA or GABAA receptor agonists during OGD, or by exposure to exogenous NMDA
      or glutamate. Pre-synaptic suppression of neuronal glutamate release by
      preconditioning, possibly via suppressed exocytic release, represents a key
      convergence point in neuroprotection during exposure to OGD and OGD-mimetics.

PMID- 22607165
TI  - A multi-site controlled trial of a cognitive skills program for mentally
      disordered offenders.
AB  - BACKGROUND: The effectiveness of offending behaviour programs in forensic mental
      health settings is not well established. Thus this study aimed to evaluate the
      Reasoning and Rehabilitation Mental Health program (R&R2 MHP) among a mentally
      disordered offender (MDO) population. METHODS: A sample of 121 adult males drawn
      from 10 forensic mental health sites completed questionnaires at baseline and
      post-treatment to assess violent attitudes, locus of control, social problem
      solving and anger. An informant measure of social and psychological functioning,
      including disruptive behaviour, was completed by unit staff at the same time. At
      three month follow-up patients completed again the violent attitudes and locus of
      control questionnaires. The data of 67 patients who participated in the group
      condition were compared with 54 waiting-list controls who received treatment as
      usual. RESULTS: 78% of group participants completed the program. In contrast to
      controls, significant treatment effects were found at outcome on self-reported
      measures of violent attitudes, rational problem-solving and anger cognitions.
      Improvements were endorsed by informant ratings of social and psychological
      functioning within the establishments. At follow-up significant treatment effects
      were found for both violent attitudes and locus of control. CONCLUSIONS: R&R2 MHP
      was effective in a sample of MDOs and had a comparatively low drop-out rate.
      Future research should use a randomized controlled design.

PMID- 22607167
TI  - Controlled cortical impact traumatic brain injury acutely disrupts wakefulness
      and extracellular orexin dynamics as determined by intracerebral microdialysis in
      mice.
AB  - Among other deficits, traumatic brain injury (TBI) causes impaired arousal and
      cognitive dysfunction. Hypothalamic orexin neuropeptides (also called
      hypocretins) regulate levels of arousal, and cerebrospinal fluid orexin levels
      are reportedly low in TBI patients. We hypothesized that TBI acutely impairs the
      dynamics of orexin release into brain interstitial fluid, and that these
      extracellular orexin levels correlate with wakefulness and motor activity. To
      test this in mice, we combined an electromagnetic controlled cortical impact
      (CCI) model of experimental TBI with dual intracerebral microdialysis using one
      catheter in the hypothalamus and one catheter in the hippocampus, plus
      electroencephalography/electromyography (EEG/EMG), and motor activity monitoring.
      Baseline data were continuously collected in tethered but relatively freely
      moving mice for 2 days. Then, ipsilateral CCI or sham surgery was performed, and
      data collection was continued for 3 additional days. At baseline, extracellular
      orexin levels in the hypothalamus showed a circadian rhythm, with peak levels
      during the dark (wake) phase, and a nadir during the light (rest) phase.
      Following CCI but not sham surgery, orexin levels were depressed in both the
      hypothalamus and hippocampus, and diurnal fluctuation amplitudes were blunted in
      the hypothalamus. At baseline, correlations of orexin with wakefulness and motor
      activity were positive and highly significant. Following CCI but not sham
      surgery, the mice exhibited reduced wakefulness and motor activity, and
      correlations between orexin and these measures were diminished. These abnormal
      orexin dynamics were associated with hypothalamic astrogliosis, but not acute
      loss of orexin neurons, as assessed by immunohistochemistry 3 days after injury.
      Future studies involving experimental manipulations of the orexin system will be
      required to determine its contribution to neurological outcomes following injury.

PMID- 22607168
TI  - Make conjugation simple: a facile approach to integrated nanostructures.
AB  - We report a facile approach to the conjugation of protein-encapsulated gold
      fluorescent nanoclusters to the iron oxide nanoparticles through catechol
      reaction. This method eliminates the use of chemical linkers and can be readily
      extended to the conjugation of biological molecules and other nanomaterials onto
      nanoparticle surfaces. The key to the success was producing water-soluble iron
      oxide nanoparticles with active catechol groups. Further, advanced electron
      microscopy analysis of the integrated gold nanoclusters and iron oxide
      nanoparticles provided direct evidence of the presence of a single fluorescent
      nanocluster per protein template. Interestingly, the integrated nanoparticles
      exhibited enhanced fluorescent emission in biological media. These studies will
      provide significantly practical value in chemical conjugation, the development of
      multifunctional nanostructures, and exploration of multifunctional nanoparticles
      for biological applications.

PMID- 22607169
TI  - How does perceived risk mediate associations between perceived safety and
      parental restriction of adolescents' physical activity in their neighborhood?
AB  - BACKGROUND: There is evidence that adolescence is a critical period of decline in
      physical activity. However, adolescents may have limited opportunities to be
      physically active outdoors if their parents are concerned about neighborhood
      safety and restrict their adolescent's physical activity within their
      neighborhood. Pathways that lead to parental restriction of adolescents' physical
      activity (constrained behavior) are under-researched. This study aimed to examine
      perceived risk as a potential mediator of associations between perceived
      safety/victimization and constrained behavior. METHODS: Cross-sectional study of
      adolescents (43% boys) aged 15-17 years (n = 270) in Melbourne, Australia.
      Parents reported perceived safety (road safety, incivilities and personal safety)
      and prior victimization in their neighborhood, perceived risk of their children
      being harmed and whether they constrained their adolescent's physical activity.
      Constrained behavior was categorized as 'avoidance' or 'defensive' behavior
      depending on a whether physical activity was avoided or modified, respectively,
      due to perceived risk. MacKinnon's product-of-coefficients test of mediation was
      used to assess potential mediating pathways between perceived
      safety/victimization and constrained behavior. RESULTS: For girls only, perceived
      risk was a significant mediator of associations between perceived road safety and
      avoidance/defensive behavior, and between perceived incivilities, perceived
      personal safety, victimization and defensive behavior. CONCLUSIONS: Associations
      between perceived safety/victimization and constrained behavior are complex.
      Findings may guide the design of interventions that aim to improve actual and
      perceived levels of safety and reduce perceptions of risk. This is of particular
      importance for adolescent girls among whom low and declining levels of physical
      activity have been observed worldwide.

PMID- 22607170
TI  - Abstracts of Beyond the Genome 2011. Washington, DC, USA. September 19-22, 2011.

PMID- 22607172
TI  - System-based factors influencing intraoperative decision-making in rectal cancer
      by surgeons: an international assessment.
AB  - AIM: Sound surgical judgement is the goal of training and experience; however,
      system-based factors may also colour selection of options by a surgeon. We
      analysed potential organizational characteristics that might influence rectal
      cancer decision-making by an experienced surgeon. METHOD: One hundred and seventy
      three international centres treating rectal cancer were invited to participate in
      a survey assessment of key treatment options for patients undergoing curative
      rectal-cancer surgery. The key organizational characteristics were analysed using
      multivariate methods for association with intra-operative surgical decision
      making. RESULTS: The response rate was 71% (123 centres). Sphincter-saving
      surgery was more likely to be performed at university hospitals (OR=3.63, P=0.01)
      and by high-caseload surgeons (OR=2.77 P=0.05). A diverting stoma was performed
      more frequently in departments with clinical audits (OR=3.06, P=0.02), and a
      diverting stoma with coloanal anastomosis was more likely in European centres
      (OR=4.14, P=0.004). One-stage surgery was less likely where there was assessment
      by a multidisciplinary team (OR=0.24, P=0.02). Multivariate analysis showed that
      university hospital, clinical audit, European centre, multidisciplinary team and
      high caseload significantly impacted on surgical decision-making. CONCLUSION:
      Treatment variance of rectal cancer surgeons appears to be significantly
      influenced by organizational characteristics and complex team-based decision
      making. System-based factors may need to be considered as a source of outcome
      variation that may impact on quality metrics.

PMID- 22607171
TI  - Solution structure of the core SMN-Gemin2 complex.
AB  - In humans, assembly of spliceosomal snRNPs (small nuclear ribonucleoproteins)
      begins in the cytoplasm where the multi-protein SMN (survival of motor neuron)
      complex mediates the formation of a seven-membered ring of Sm proteins on to a
      conserved site of the snRNA (small nuclear RNA). The SMN complex contains the SMN
      protein Gemin2 and several additional Gemins that participate in snRNP
      biosynthesis. SMN was first identified as the product of a gene found to be
      deleted or mutated in patients with the neurodegenerative disease SMA (spinal
      muscular atrophy), the leading genetic cause of infant mortality. In the present
      study, we report the solution structure of Gemin2 bound to the Gemin2-binding
      domain of SMN determined by NMR spectroscopy. This complex reveals the structure
      of Gemin2, how Gemin2 binds to SMN and the roles of conserved SMN residues near
      the binding interface. Surprisingly, several conserved SMN residues, including
      the sites of two SMA patient mutations, are not required for binding to Gemin2.
      Instead, they form a conserved SMN/Gemin2 surface that may be functionally
      important for snRNP assembly. The SMN-Gemin2 structure explains how Gemin2 is
      stabilized by SMN and establishes a framework for structure-function studies to
      investigate snRNP biogenesis as well as biological processes involving Gemin2
      that do not involve snRNP assembly.

PMID- 22607173
TI  - Parsley and immunomodulation.

PMID- 22607174
TI  - Stability of T-cell lineages in autoimmune diseases.

PMID- 22607175
TI  - Management of inflammatory bowel disease: past, present and future.

PMID- 22607177
TI  - The evolution of the danger theory. Interview by Lauren Constable, Commissioning
      Editor.
AB  - Polly Matzinger, now Chief of the Ghost Laboratory and the section on T-cell
      Tolerance and Memory at the NIH, has previously worked as a bartender, carpenter,
      jazz musician, Playboy bunny and dog trainer. She completed her PhD at the
      University of California, San Diego (USA) and was a postdoctoral fellow at the
      University of Cambridge (UK). She has worried for years that the dominant model
      of immunity does not explain a wealth of accumulated data and has recently
      suggested an alternative, the danger model, which suggests that the immune system
      is far less concerned with things that are foreign than with those that do
      damage. This model, whose two major tenets Matzinger admits were thought up in a
      bath and on a field while herding sheep, has very few assumptions and yet
      "explains most of what the immune system seems to do right, as well as most of
      what it appears to do wrong", covering such areas as transplantation,
      autoimmunity and the immunobiology of tumors. The model has been the subject of a
      BBC Horizon film and has featured in two other films about immunity and countless
      articles in both the scientific and the lay press. In her spare time, Matzinger
      trains border collies for competitive shepherding trials and, in her own words,
      "composes songs that are not really worth listening to, and worries about the
      next major question in the immune system", namely "once it decides to respond,
      how does the immune system know what kind of response to make?"

PMID- 22607178
TI  - Tofacitinib for the treatment of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects
      approximately 1% of the worldwide population. It primarily targets the synovial
      membrane of joints, leading to a synovial proliferation, joint cartilage lesion
      and erosions in the adjacent bone tissue. The disease is usually progressive and
      if the inflammatory process is not adequately suppressed, joint deformity takes
      place, leading to a significant functional disability and work incapacity. Over
      the last decade, biological therapy was established as a major step towards
      disease control in those patients who experienced failure after treatment with
      disease-modifying antirheumatic drugs. Despite the growing number of biological
      agents with different immunological targets, a significant number of patients do
      not receive appropriate disease control, or have the use of these agents limited
      because of adverse events. As such, the search for new molecules with a higher
      efficacy and better safety profile is ongoing. This article focuses on a new
      drug, tofacitinib, which is a synthetic disease-modifying antirheumatic drug for
      treatment of RA. Preclinical studies in arthritis and transplantation animal
      models are reviewed as a background for the possible use of tofacitinib treatment
      in humans. Four Phase II (one A and three B dose-ranging) trials lasting from 6
      to 24 weeks in RA patients showed significant American College of Rheumatology 20
      improvements as early as week 2 and sustained at week 24 in two studies.
      Tofacitinib Phase III studies in RA are included in a clinical program called
      'ORAL Trials'. Long-term follow-up from ongoing studies will contribute to a more
      accurate tofacitinib efficacy and safety profile. Trials in other illness such as
      psoriasis, psoriatic arthritis, renal transplant rejection prevention,
      inflammatory bowel diseases and dry eye are underway.

PMID- 22607179
TI  - Autoimmunity in focus: from mechanisms to treatment.
AB  - The 5th Asian Congress on Autoimmunity took place in Suntec City, Singapore, on
      the 17-19 November 2011 under the presidency of Yehuda Shoenfeld (Chaim Sheba
      Medical Center, Ramat Gan, Israel). Senior investigators from a range of fields-
      including immunology, autoimmunity, rheumatology, neurology and hepatology-
      attended the conference. The scientific program placed an emphasis on the
      pathogenesis, genetic basis and mechanistic aspects of autoimmune diseases, as
      well as their clinical outcomes and treatment options. Particular focus was
      placed on systemic lupus erythematosus, rheumatoid arthritis, Type I diabetes,
      antiphospholipid syndrome and autoimmune hepatitis. Participants from over 50
      countries attended the conference.

PMID- 22607180
TI  - Medication adherence in patients with rheumatoid arthritis: a critical appraisal
      of the existing literature.
AB  - Adherence to medication in patients with rheumatoid arthritis is low, varying
      from 30 to 80%. Improving adherence to therapy could therefore dramatically
      improve the efficacy of drug therapy. Although indicators for suboptimal
      adherence can be useful to identify nonadherent patients, and could function as
      targets for adherence-improving interventions, no indicators are yet found to be
      consistently and strongly related to nonadherence. Despite this, nonadherence
      behavior could conceptually be categorized into two subtypes: unintentional (due
      to forgetfulness, regimen complexity or physical problems) and intentional (based
      on the patient's decision to take no/less medication). In case of intentional
      nonadherence, patients seem to make a benefit-risk analysis weighing the
      perceived risks of the treatment against the perceived benefits. This weighing
      process may be influenced by the patient's beliefs about medication, the
      patient's self-efficacy and the patient's knowledge of the disease. This
      implicates that besides tackling practical barriers, clinicians should be
      sensitive to patient's personal beliefs that may impact medication adherence.

PMID- 22607181
TI  - Utilizing registries in systemic lupus erythematosus clinical research.
AB  - Systemic lupus erythematosus is a complex and heterogeneous autoimmune disease
      with a relatively low incidence. Clinical research in this disease at individual
      centers is complicated by the difficulty of accruing enough patient numbers. In
      this context, the development of cohorts and multi-institutional registries
      during the last decades has allowed an increase in knowledge regarding the
      clinical course and management of this disease. This article aims to describe the
      main study designs linked to lupus registries and to give an overview of the main
      international registries and cohorts, as well as their principal achievements in
      the context of this complex entity.

PMID- 22607182
TI  - Merging experimental data and in silico analysis: a systems-level approach to
      autoimmune disease and cancer.
AB  - Systems biology, or more specifically network biology, is driven by the
      assumption that a single gene is seldom accountable for a discrete biological
      function. In other words, studying molecules one by one will not satisfactorily
      address the function of complex organisms and/or predict the consequences of
      biological interactions. On the other hand, interpretation of large-scale data
      sets provided by the development of high-throughput techniques, which form the
      core of systems-level analysis, does raise methodological issues. Enhancement of
      such methodologies will be of key importance for health research in the coming
      years, as studies have provided convincing evidence that integration of
      experimental data with in silico analysis can lead to scientific advances that
      lay the foundations for translational research applied to human disease. These
      topics have been discussed in the present review and two case studies
      exemplifying our experience in the field have also been presented. We suggest
      that the process of integrating in silico analysis (dry laboratory) with
      experimental verification (wet laboratory) is likely to have a broad impact on
      the study of biological systems in physiology and disease.

PMID- 22607184
TI  - Immune response to CMV in solid organ transplant recipients: current concepts and
      future directions.
AB  - Despite advances in immunosuppression and antiviral therapy, CMV continues to be
      a significant opportunistic pathogen adversely affecting the outcome of solid
      organ transplantation (SOT) recipients. While a significant proportion of CMV
      disease is caused by reactivation of latent virus, the risk is highest among CMV
      donor+ and recipient- SOT patients. CMV is responsible for both direct (e.g.,
      pneumonitis, colitis) and indirect (e.g., rejection, atherosclerosis) morbidity
      and mortality. Healthy CMV-seropositive individuals have a high frequency of CMV
      specific CD4(+) and CD8(+) T cells that provide immune protection by limiting CMV
      reactivation and replication. Changes to the innate and adaptive immune system
      from immunosuppressive therapy following SOT contribute to CMV disease
      pathogenesis. CMV disease after SOT is associated with poorer outcomes, thus
      novel strategies to prevent it are an area of active research. In this article,
      we review the current state of knowledge on the immune response to CMV following
      SOT.

PMID- 22607183
TI  - Allogeneic hematopoietic cell transplantation for myelodysplastic syndrome: the
      past decade.
AB  - Hematopoietic cell transplantation (HCT) is the only therapy with curative
      potential for patients with myelodysplastic syndrome. Many conditioning regimens
      have been developed that, along with the use of cord blood or HLA-haploidentical
      donors, allow doctors to offer HCT to a growing proportion of patients. New
      classification schemes identify more narrowly characterized risk groups, which
      may facilitate decisions with regard to HCT. Disease stage and cytogenetics
      remain the major determinants of HCT outcome. The use of peripheral blood
      progenitor cells may offer an advantage over marrow for engraftment and relapse
      prevention, but graft-versus-host disease remains a problem. The age of patients
      undergoing HCT has increased significantly over the past 25 years, and comorbid
      conditions are the major patient characteristic impacting transplant success.
      Recent studies show that drugs used in the non-HCT setting may be beneficial in
      the context of HCT.

PMID- 22607186
TI  - Thermogelling chitosan-g-(PAF-PEG) aqueous solution as an injectable scaffold.
AB  - The present study reports on a thermogelling poly(ethylene glycol)-poly(L-alanine
      co-L-phenyl alanine) grafted chitosan (CS-g-(PAF-PEG)) system, focusing on phase
      diagram, transition mechanism, and in vivo gel duration. The sol-to-gel
      transition temperature decreased from 27 to 11  degrees C as the concentration
      increased from 4.0 wt % to 9.0 wt %. The polymer formed micelles with 10-50 nm in
      diameter at 10  degrees C and formed large aggregates ranging from hundreds to
      thousands of nanometers in size as the temperature increased from 10 to 35 
      degrees C, suggesting that an extensive molecular aggregation might be involved
      in the sol-to-gel transition. To study the transition mechanism on a molecular
      level, we investigated pH, circular dichroism spectra, and (13)C NMR spectra of
      the CS-g-(PAF-PEG) aqueous solution as a function of temperature. As the
      temperature increased, deprotonation of the chitosan and dehydration of the PEG
      were suggested, whereas the alpha-helical secondary structure of PAF was slightly
      changed in the sol-to-gel transition temperature range of 10-50  degrees C. A gel
      was formed in situ after injecting the CS-g-(PAF-PEG) aqueous solution into the
      subcutaneous layer of rats. About 60-70% of the gel was eliminated in 1 week, and
      the remaining gel was completely cleared from the implant site in 14 days. The
      results indicate the potential of CS-g-(PAF-PEG) as a promising short-term
      carrier for pharmaceutical agents.

PMID- 22607187
TI  - Characterization and solubilization of pyrrole-imidazole polyamide aggregates.
AB  - To optimize the biological activity of pyrrole-imidazole polyamide DNA-binding
      molecules, we characterized the aggregation propensity of these compounds through
      dynamic light scattering and fractional solubility analysis. Nearly all studied
      polyamides were found to form measurable particles 50-500 nm in size under
      biologically relevant conditions, while HPLC-based analyses revealed solubility
      trends in both core sequences and peripheral substituents that did not correlate
      with overall ionic charge. The solubility of both hairpin and cyclic polyamides
      was increased upon addition of carbohydrate solubilizing agents, in particular, 2
      hydroxypropyl-beta-cyclodextrin (HpbetaCD). In mice, the use of HpbetaCD allowed
      for improved injection conditions and subsequent investigations of the
      availability of polyamides in mouse plasma to human cells. The results of these
      studies will influence the further design of Py-Im polyamides and facilitate
      their study in animal models.

PMID- 22607188
TI  - Genetic variation and metabolic pathway intricacy govern the active compound
      content and quality of the Chinese medicinal plant Lonicera japonica thunb.
AB  - BACKGROUND: Traditional Chinese medicine uses various herbs for the treatment of
      various diseases for thousands of years and it is now time to assess the
      characteristics and effectiveness of these medicinal plants based on modern
      genetic and molecular tools. The herb Flos Lonicerae Japonicae (FLJ or Lonicera
      japonica Thunb.) is used as an anti-inflammatory agent but the chemical quality
      of FLJ and its medicinal efficacy has not been consistent. Here, we analyzed the
      transcriptomes and metabolic pathways to evaluate the active medicinal compounds
      in FLJ and hope that this approach can be used for a variety of medicinal herbs
      in the future. RESULTS: We assess transcriptomic differences between FLJ and L.
      japonica Thunb. var. chinensis (Watts) (rFLJ), which may explain the variable
      medicinal effects. We acquired transcriptomic data (over 100 million reads) from
      the two herbs, using RNA-seq method and the Illumina GAII platform. The
      transcriptomic profiles contain over 6,000 expressed sequence tags (ESTs) for
      each of the three flower development stages from FLJ, as well as comparable
      amount of ESTs from the rFLJ flower bud. To elucidate enzymatic divergence on
      biosynthetic pathways between the two varieties, we correlated genes and their
      expression profiles to known metabolic activities involving the relevant active
      compounds, including phenolic acids, flavonoids, terpenoids, and fatty acids. We
      also analyzed the diversification of genes that process the active compounds to
      distinguish orthologs and paralogs together with the pathways concerning
      biosynthesis of phenolic acid and its connections with other related pathways.
      CONCLUSIONS: Our study provides both an initial description of gene expression
      profiles in flowers of FLJ and its counterfeit rFLJ and the enzyme pool that can
      be used to evaluate FLJ quality. Detailed molecular-level analyses allow us to
      decipher the relationship between metabolic pathways involved in processing
      active medicinal compounds and gene expressions of their processing enzymes. Our
      evolutionary analysis revealed specific functional divergence of orthologs and
      paralogs, which lead to variation in gene functions that govern the profile of
      active compounds.

PMID- 22607189
TI  - The association between health anxiety and disgust reactions in a contamination
      based behavioral approach task.
AB  - Existing evidence suggests that disgust is an important affective process related
      to health anxiety. The present study sought to determine the contribution of
      health anxiety symptoms in the prediction of disgust and behavioral avoidance in
      a large, nonclinical sample (N=156). Regression analyses showed that overall
      health anxiety symptoms predicted disgust on a behavioral approach task
      independent of gender, negative affect, and fear of contamination. Particularly,
      health anxiety-related reassurance seeking was found to be uniquely associated
      with disgust and behavioral avoidance after controlling for the aforementioned
      covariates. In addition, the interaction between health anxiety and contamination
      fear was tested, and remained significant when controlling for gender and
      negative affect. These results suggest that heightened contamination fear is
      associated with elevated disgust reactions such that high levels of health
      anxiety leads even those low in contamination fear to be disgusted during a
      behavioral task. These results are in line with previous research on the role of
      disgust in health anxiety.

PMID- 22607190
TI  - Calorimetric determination of rate constants and enthalpy changes for zero-order
      reactions.
AB  - Calorimetry is a general method for determination of the rates of zero-order
      processes, but analysis of the data for the rate constant and reaction enthalpy
      is difficult because these occur as a product in the rate equation so evaluation
      of one requires knowledge of the other. Three methods for evaluation of both
      parameters, without prior knowledge, are illustrated with examples and compared
      with literature data. Method 1 requires the reaction to be studied in two buffers
      with different enthalpies of ionization. Method 2 is based on calculation of
      reaction enthalpy from group additivity functions. Method 3 applies when reaction
      progresses to completion. The methods are applied to the enzymatic hydrolysis of
      urea, the hydrolysis of acetylsalicylic acid, and the photodegradation of
      nifedipine, respectively.

PMID- 22607191
TI  - Family of enhanced photoacoustic imaging agents for high-sensitivity and
      multiplexing studies in living mice.
AB  - Photoacoustic imaging is a unique modality that overcomes to a great extent the
      resolution and depth limitations of optical imaging while maintaining relatively
      high contrast. However, since many diseases will not manifest an endogenous
      photoacoustic contrast, it is essential to develop exogenous photoacoustic
      contrast agents that can target diseased tissue(s). Here we present a family of
      novel photoacoustic contrast agents that are based on the binding of small
      optical dyes to single-walled carbon nanotubes (SWNT-dye). We synthesized five
      different SWNT-dye contrast agents using different optical dyes, creating five
      "flavors" of SWNT-dye nanoparticles. In particular, SWNTs that were coated with
      either QSY(21) (SWNT-QSY) or indocyanine green (SWNT-ICG) exhibited over 100
      times higher photoacoustic contrast in living animals compared to plain SWNTs,
      leading to subnanomolar sensitivities. We then conjugated the SWNT-dye conjugates
      with cyclic Arg-Gly-Asp peptides to molecularly target the alpha(v)beta(3)
      integrin, which is associated with tumor angiogenesis. Intravenous administration
      of these tumor-targeted imaging agents to tumor-bearing mice showed significantly
      higher photoacoustic signal in the tumor than in mice injected with the
      untargeted contrast agent. Finally, we were able to spectrally separate the
      photoacoustic signals of SWNT-QSY and SWNT-ICG in living animals injected
      subcutaneously with both particles in the same location, opening the possibility
      for multiplexing in vivo studies.

PMID- 22607192
TI  - Acupuncture to improve live birth rates for women undergoing in vitro
      fertilization: a protocol for a randomized controlled trial.
AB  - BACKGROUND: IVF is a costly treatment option for women, their partners, and the
      public. Therefore new therapies that improve reproductive and health outcomes are
      highly desirable. There is a growing body of research evaluating the effect of
      acupuncture administered during IVF, and specifically on the day of embryo
      transfer (ET). Many trials are heterogeneous and results inconsistent. There
      remains insufficient evidence to determine if acupuncture can enhance live birth
      rates when used as an adjunct to IVF treatment.The study will determine the
      clinical effectiveness of acupuncture with improving the proportion of women
      undergoing IVF having live births. Other objectives include: determination of the
      cost effectiveness of IVF with acupuncture; and examination of the personal and
      social context of acupuncture in IVF patients, and examining the reasons why the
      acupuncture may or may not have worked. METHODS: We will conduct a randomized
      controlled trial of acupuncture compared to placebo acupuncture.Inclusion
      criteria include: women aged less than 43 years; undergoing a fresh IVF or ICSI
      cycle; and restricted to women with the potential for a lower live birth rate
      defined as two or more previous unsuccessful ETs; and unsuccessful clinical
      pregnancies of quality embryos deemed by the embryologist to have been suitable
      for freezing by standard criteria. Women will be randomized to acupuncture or
      placebo acupuncture. Treatment is administered on days 6 to 8 of the stimulated
      cycle and two treatments on the day of ET. A non-randomized cohort of women not
      using acupuncture will be recruited to the study. The primary study outcome is
      the proportion of women reporting a live birth. Secondary outcomes include the
      proportion of women reporting a clinical pregnancy miscarriage prior to 12 weeks,
      quality of life, and self-efficacy. The sample size of the study is 1,168 women,
      with the aim of detecting a 7% difference in live births between groups (P =
      0.05, 80% power). DISCUSSION: There remains a need for further research to add
      significant new knowledge to defining the exact role of certain acupuncture
      protocols in the management of infertility requiring IVF from a clinical and cost
      effectiveness perspective. CLINICAL TRIAL REGISTRATION: Australian and New
      Zealand Clinical Trial Registry ACTRN12611000226909.

PMID- 22607193
TI  - Pattern recognition receptors in equine endotoxaemia and sepsis.
AB  - Pattern recognition receptors (PRRs) on host cells detect pathogens to activate
      innate immunity which, in turn, initiates inflammatory and adaptive immune
      responses. Successful activation of PRRs is, therefore, critical to controlling
      infections and driving pathogen-specific adaptive immunity, but overactivity of
      PRRs causes systemic inflammation, which is detrimental to the host. Here we
      review the PRR literature as it relates to horses and speculate on the role PRRs
      may play in sepsis and endotoxaemia.

PMID- 22607194
TI  - GATA6 and FOXA2 regulate Wnt6 expression during extraembryonic endoderm
      formation.
AB  - One of the earliest epithelial-to-mesenchymal transitions in mouse embryogenesis
      involves the differentiation of inner cell mass cells into primitive and then
      into parietal endoderm. These processes can be recapitulated in vitro using F9
      teratocarcinoma cells, which differentiate into primitive endoderm when treated
      with retinoic acid (RA) and into parietal endoderm with subsequent treatment with
      dibutyryl cyclic adenosine monophosphate (db-cAMP). Our previous work on how
      primitive endoderm develops revealed that the Wnt6 gene is upregulated by RA,
      leading to the activation of the canonical WNT-beta-catenin pathway. The
      mechanism by which Wnt6 is regulated was not determined, but in silico analysis
      of the human WNT6 promoter region had suggested that the GATA6 and FOXA2
      transcription factors might be involved [1]. Subsequent analysis determined that
      both Gata6 and Foxa2 mRNA are upregulated in F9 cells treated with RA or RA and
      db-cAMP. More specifically, overexpression of Gata6 or Foxa2 alone induced
      molecular and morphological markers of primitive endoderm, which occurred
      concomitantly with the upregulation of the Wnt6 gene. Gata6- or Foxa2
      overexpressing cells were also found to have increased levels in T-cell factor
      (TCF)-dependent transcription, and when these cells were treated with db-cAMP,
      they developed into parietal endoderm. Chromatin immunoprecipitation analysis
      revealed that GATA6 and FOXA2 were bound to the Wnt6 promoter, and overexpression
      studies showed that these transcription factors were sufficient to switch on the
      gene expression of a Wnt6 reporter construct. Together, these results provide
      evidence for the direct regulation of Wnt6 that leads to the activation of the
      canonical WNT-beta-catenin pathway and subsequent induction of primitive
      extraembryonic endoderm.

PMID- 22607195
TI  - Medication reviews.
AB  - Recent years have seen a formalization of medication review by pharmacists in all
      settings of care. This article describes the different types of medication review
      provided in primary care in the UK National Health Service (NHS), summarizes the
      evidence of effectiveness and considers how such reviews might develop in the
      future. Medication review is, at heart, a diagnostic intervention which aims to
      identify problems for action by the prescriber, the clinician conducting the
      review, the patient or all three but can also be regarded as an educational
      intervention to support patient knowledge and adherence. There is good evidence
      that medication review improves process outcomes of prescribing including reduced
      polypharmacy, use of more appropriate medicines formulation and more appropriate
      choice of medicine. When 'harder' outcome measures have been included, such as
      hospitalizations or mortality in elderly patients, available evidence indicates
      that whilst interventions could improve knowledge and adherence they did not
      reduce mortality or hospital admissions with one study showing an increase in
      hospital admissions. Robust health economic studies of medication reviews remain
      rare. However a review of cost-effectiveness analyses of medication reviews found
      no studies in which the cost of the intervention was greater than the benefit.
      The value of medication reviews is now generally accepted despite lack of robust
      research evidence consistently demonstrating cost or clinical effectiveness
      compared with traditional care. Medication reviews can be more effectively
      deployed in the future by targeting, multi-professional involvement and paying
      greater attention to medicines which could be safely stopped.

PMID- 22607196
TI  - Oroxylin A improves the sensitivity of HT-29 human colon cancer cells to 5-FU
      through modulation of the COX-2 signaling pathway.
AB  - 5-Fluorouracil (5-FU) is a principal drug for the treatment of colorectal cancer.
      Due to its low response and high toxicity, synergistic effects of 5-FU in
      combination with other drugs have been widely researched. This study investigated
      whether oroxylin A improved the sensitivity of HT-29 human colon cancer cells to
      5-FU. A correlation between COX-2 inhibition by oroxylin A and a synergistic
      effect of 5-FU on the growth of HT-29 cells was observed, and a COX-2 pathway for
      this effect was recognized; oroxylin A evidently elevated the level of reactive
      oxygen species in HT-29 cells, which subsequently inhibited COX-2 expression and
      enhanced the susceptibility of HT-29 cells to 5-FU. Likely also related to COX-2
      inhibition, oroxylin A decreased PGE(2) levels in HT-29 cells. The synergistic
      effect of 5-FU induced by oroxylin A was also found in the suppression of Bcl-2
      and in the activation of P53, Bax, PARP, and procaspase-3 proteins in HT-29
      cells. Ultimately, a combination of 5-FU with oroxylin A significantly reduced
      the growth of HT-29 tumors in nude mice compared with treatment with 5-FU or
      oroxylin A alone. In conclusion, a combination of 5-FU and oroxylin A has a
      significant synergistic effect in the inhibition of HT-29 cell proliferation in
      vitro and controls HT-29 tumor growth in vivo. This synergistic effect may be
      mainly related to COX-2 inhibition by oroxylin A in HT-29 cells.

PMID- 22607198
TI  - Enacting death: contested practices in the organ donation clinic.
AB  - Based on the fieldwork at two Norwegian Intensive Care Units, we wish to discuss
      the sometimes inconsistent manner in which death is handled, determined and made
      real by nurses and other healthcare personnel in high-tech hospital situations.
      These discrepancies draw our attention towards different ways of attending to the
      dying and dead and views about appropriate or inappropriate codes of professional
      behaviour. As we will argue below, the analytical tools developed by Annemarie
      Mol are useful for sharpening our understanding of the enactment of multiple
      ontologies of death as they are enacted within the ICU. Annemarie Mol and John
      Law's notion of 'ontological politics' increases our awareness about the non
      arbitrary way some but not other practices are considered self-evident whereas
      others are denigrated as muddled and illogical. 

PMID- 22607197
TI  - Construction of bilayered tissue-engineered skin with human amniotic mesenchymal
      cells and human amniotic epithelial cells.
AB  - Human amniotic mesenchymal cells (hAMCs) and human amniotic epithelial cells
      (hAECs) have attracted increasing attention in recent years as a possible reserve
      of stem cells that may be useful for clinical application in regenerative
      medicine. The object of this study was to establish a new model for
      reconstruction of bilayered tissue-engineered (TE) skin with hAMCs and hAECs
      (amniotic cells TE skin, AC-TE skin). We studied these two types of cells and
      confirmed that they possessed the properties of stem cells. Mesenchymal-epidermal
      interactions are responsible for organogenesis. On the basis of this mechanism,
      we modified the constructing methods of traditional TE skin (TE skin with human
      fibroblasts and keratinocytes) and then established a new bilayered TE skin-AC-TE
      skin. Histological and immunochemical methods were carried out to assess AC-TE
      skin. The results showed that AC-TE skin was similar in morphology to human skin
      which had stratified epidermis and underlying dermis. AC-TE skin expressed
      proliferative cells marker Ki67 and epithelial stem cells marker K19; moreover,
      the constructed AC-TE skin could successfully repair full thickness skin defects
      on athymic mice. Our findings suggest that AC-TE skin is a useful skin equivalent
      which has good application prospects in regenerative medicine.

PMID- 22607199
TI  - Evidence for a systemic regulation of neurotrophin synthesis in response to
      peripheral nerve injury.
AB  - Up-regulation of neurotrophin synthesis is an important mechanism of peripheral
      nerve regeneration after injury. Neurotrophin expression is regulated by a
      complex series of events including cell interactions and multiple molecular
      stimuli. We have studied neurotrophin synthesis at 2 weeks time-point in a
      transvertebral model of unilateral or bilateral transection of sciatic nerve in
      rats. We have found that unilateral sciatic nerve transection results in the
      elevation of nerve growth factor (NGF) and NT-3, but not glial cell-line derived
      neurotrophic factor or brain-derived neural factor, in the uninjured nerve on the
      contralateral side, commonly considered as a control. Bilateral transection
      further increased NGF but not other neurotrophins in the nerve segment distal to
      the transection site, as compared to the unilateral injury. To further
      investigate the distinct role of NGF in regeneration and its potential for
      peripheral nerve repair, we transduced isogeneic Schwann cells with NGF-encoding
      lentivirus and transplanted the over-expressing cells into the distal segment of
      a transected nerve. Axonal regeneration was studied at 2 weeks time-point using
      pan-neuronal marker NF-200 and found to directly correlate with NGF levels in the
      regenerating nerve.

PMID- 22607200
TI  - Physiological significance of alternatively spliced exon combinations of the
      single-copy gene class A chitin synthase in the insect Ostrinia furnacalis
      (Lepidoptera).
AB  - Insect chitin synthase is an essential enzyme involved in chitin biosynthesis in
      insects. Chitin synthase A (CHSA) is expressed in different insect tissues during
      different developmental stages. CHSA contains alternative-splicing exons that
      allow tissue- and development-specific chitin synthesis. Here, we report that
      OfCHSA from the lepidopteran Ostrinia furnacalis contains two alternative
      splicing exons, exons 2a and 2b and exons 19a and 19b. Although four combinations
      of these exons are theoretically possible, we found that transcripts containing
      exon 2a were dominant during most developmental stages, including embryonic
      development, larval-larval moulting, the larval-pupal transition and pupal-adult
      metamorphosis. Unexpectedly, 2b-containing transcripts were much more responsive
      to 20-hydroxyecdysone regulation than 2a-containing ones, suggesting that
      although OfCHSA isoforms encoded by 2b-containing transcripts are normally
      expressed at very low levels, they play unique roles. Spliced exons 2a and 2b
      have also been observed in Bombyx mori; therefore, this work provides new
      insights into the regulation of insect chitin synthase, particularly in
      lepidopteran insects.

PMID- 22607201
TI  - Enhancement of thioredoxin/glutaredoxin-mediated L-cysteine synthesis from S
      sulfocysteine increases L-cysteine production in Escherichia coli.
AB  - BACKGROUND: Escherichia coli has two L-cysteine biosynthetic pathways; one is
      synthesized from O-acetyl L-serine (OAS) and sulfate by L-cysteine synthase
      (CysK), and another is produced via S-sulfocysteine (SSC) from OAS and
      thiosulfate by SSC synthase (CysM). SSC is converted into L-cysteine and sulfite
      by an uncharacterized reaction. As thioredoxins (Trx1 and Trx2) and glutaredoxins
      (Grx1, Grx2, Grx3, Grx4, and NrdH) are known as reductases of peptidyl
      disulfides, overexpression of such reductases might be a good way for improving L
      cysteine production to accelerate the reduction of SSC in E. coli. RESULTS:
      Because the redox enzymes can reduce the disulfide that forms on proteins, we
      first tested whether these enzymes catalyze the reduction of SSC to L-cysteine.
      All His-tagged recombinant enzymes, except for Grx4, efficiently convert SSC into
      L-cysteine in vitro. Overexpression of Grx1 and NrdH enhanced a 15-40% increase
      in the E. coliL-cysteine production. On the other hand, disruption of the cysM
      gene cancelled the effect caused by the overexpression of Grx1 and NrdH,
      suggesting that its improvement was due to the efficient reduction of SSC under
      the fermentative conditions. Moreover, L-cysteine production in knockout mutants
      of the sulfite reductase genes (DeltacysI and DeltacysJ) and the L-cysteine
      synthase gene (DeltacysK) each decreased to about 50% of that in the wild-type
      strain. Interestingly, there was no significant difference in L-cysteine
      production between wild-type strain and gene deletion mutant of the upstream
      pathway of sulfite (DeltacysC or DeltacysH). These results indicate that sulfite
      generated from the SSC reduction is available as the sulfur source to produce
      additional L-cysteine molecule. It was finally found that in the E. coliL
      cysteine producer that co-overexpress glutaredoxin (NrdH), sulfite reductase
      (CysI), and L-cysteine synthase (CysK), there was the highest amount of L
      cysteine produced per cell. CONCLUSIONS: In this work, we showed that Grx1 and
      NrdH reduce SSC to L-cysteine, and the generated sulfite is then utilized as the
      sulfur source to produce additional L-cysteine molecule through the sulfate
      pathway in E. coli. We also found that co-overexpression of NrdH, CysI, and CysK
      increases L-cysteine production. Our results propose that the enhancement of
      thioredoxin/glutaredoxin-mediated L-cysteine synthesis from SSC is a novel method
      for improvement of L-cysteine production.

PMID- 22607203
TI  - Face-centered-cubic large-pore periodic mesoporous organosilicas with unsaturated
      and aromatic bridging groups.
AB  - Large-pore ethenylene-bridged (-CH?CH-) and phenylene-bridged (-C(6)H(4)-)
      periodic mesoporous organosilicas (PMOs) with face-centered-cubic structure (Fm3m
      symmetry) of spherical mesopores were synthesized at 7  degrees C at low acid
      concentration (0.1 M HCl) using Pluronic F127 triblock copolymer surfactant in
      the presence of aromatic swelling agents (1,3,5-trimethylbenzene, xylenes-isomer
      mixture, and toluene). In particular, this work reports an unprecedented block
      copolymer-templated well-ordered ethenylene-bridged PMO with cubic structure of
      spherical mesopores and an unprecedented block-copolymer-templated face-centered
      cubic phenylene-bridged PMO, which also has an exceptionally large unit-cell size
      and pore diameter. The unit-cell parameters of 30 and 25 nm and the mesopore
      diameters of 14 and 11 nm (nominal BJH-KJS pore diameters of 12-13 and 9 nm) were
      obtained for ethenylene-bridged and phenylene-bridged PMOs, respectively. Under
      the considered reaction conditions, the unit-cell parameters and pore diameters
      were found to be similar when the three different methyl-substituted benzene
      swelling agents were employed, although the degree of structural ordering
      appeared to improve for phenylene-bridged PMOs in the sequence of decreased
      number of methyl groups on the benzene ring.

PMID- 22607202
TI  - Correlating anterior insula gray matter volume changes in young people with
      clinical and neurocognitive outcomes: an MRI study.
AB  - BACKGROUND: The anterior insula cortex is considered to be both the structural
      and functional link between experience, affect, and behaviour. Magnetic resonance
      imaging (MRI) studies have shown changes in anterior insula gray matter volume
      (GMV) in psychosis, bipolar, depression and anxiety disorders in older patients,
      but few studies have investigated insula GMV changes in young people. This study
      examined the relationship between anterior insula GMV, clinical symptom severity
      and neuropsychological performance in a heterogeneous cohort of young people
      presenting for mental health care. METHODS: Participants with a primary diagnosis
      of depression (n = 43), bipolar disorder (n = 38), psychosis (n = 32), anxiety
      disorder (n = 12) or healthy controls (n = 39) underwent structural MRI scanning,
      and volumetric segmentation of the bilateral anterior insula cortex was performed
      using the FreeSurfer application. Statistical analysis examined the linear and
      quadratic correlations between anterior insula GMV and participants' performance
      in a battery of clinical and neuropsychological assessments. RESULTS: Compared to
      healthy participants, patients had significantly reduced GMV in the left anterior
      insula (t = 2.05, p = .042) which correlated with reduced performance on a
      neuropsychological task of attentional set-shifting (rho = .32, p = .016).
      Changes in right anterior insula GMV was correlated with increased symptom
      severity (r = .29, p = .006) and more positive symptoms (r = .32, p = .002).
      CONCLUSIONS: By using the novel approach of examining a heterogeneous cohort of
      young depression, anxiety, bipolar and psychosis patients together, this study
      has demonstrated that insula GMV changes are associated with neurocognitive
      deficits and clinical symptoms in such young patients.

PMID- 22607204
TI  - Immune mediators of protective and pathogenic immune responses in patients with
      mild and fatal human monocytotropic ehrlichiosis.
AB  - BACKGROUND: Ehrlichia chaffeensis is a bacterial pathogen that causes fatal human
      monocytic ehrlichiosis (HME) that mimic toxic shock-like syndrome. Murine studies
      indicate that over activation of cellular immunity followed by immune suppression
      plays a central role in mediating tissue injury and organ failure during fatal
      HME. However, there are no human studies that examine the correlates of
      resistance or susceptibility to severe and fatal HME. RESULTS: In this study, we
      compared the immune responses in two patients with mild/non fatal and
      severe/fatal HME who had marked lymphopenia, thrombocytopenia and elevated liver
      enzymes. The levels of different immunological factors in the blood of those
      patients were examined and compared to healthy controls. Our data showed that
      fatal HME is associated with defective production of Th1 cytokines such as (
      IFNgamma and IL-2), increased anti-inflammatory (IL-10 and IL-13) and pro
      inflammatory (TNF-alpha, IL-1alpha, IL-1beta, and IL-6) cytokines, increased
      levels of macrophages, T cells, and NK cells chemokines such as MCP-1, MIP
      1alpha, MIP-1beta, but not RANTES and IP-10, increased levels of neutrophils
      chemokine and growth factor (IL-8 and G-CSF), and elevated expression of tumor
      necrosis factor receptor (TNFR), and toll like receptors 2 and 4 compared to
      patients with non fatal HME and healthy controls. CONCLUSIONS: Fatal Ehrlichia
      induced toxic shock is associated with defective Th1 responses, possible immune
      suppression mediated by IL-10. In addition, marked leukopenia observed in
      patients with fatal disease could be attributed to enhanced apoptosis of
      leukocytes and/or elevated chemokine production that could promote migration of
      immune cells to sites of infection causing tissue injury.

PMID- 22607205
TI  - Synthesis and antimitotic and tubulin interaction profiles of novel pinacol
      derivatives of podophyllotoxins.
AB  - Several pinacol derivatives of podophyllotoxins bearing different side chains and
      functions at C-7 were synthesized through reductive cross-coupling of
      podophyllotoxone and several aldehydes and ketones. While possessing a
      hydroxylated chain at C-7, the compounds retained their respective hydroxyl group
      with either the 7alpha (podo) or 7beta (epipodo) configuration. Along with
      pinacols, some C-7 alkylidene and C-7 alkyl derivatives were also prepared.
      Cytotoxicities against neoplastic cells followed by cell cycle arrest and
      cellular microtubule disruption were evaluated and mechanistically characterized
      through tubulin polymerization inhibition and assays of binding to the colchicine
      site. Compounds of the epipodopinacol (7beta-OH) series behaved similarly to
      podophyllotoxin in all the assays and proved to be the most potent inhibitors.
      Significantly, 7alpha-isopropyl-7-deoxypodophyllotoxin (20), without any hydroxyl
      function, appeared as a promising lead compound for a novel type of tubulin
      polymerization inhibitors. Experimental results were in overall agreement with
      modeling and docking studies performed on representative compounds of each
      series.

PMID- 22607206
TI  - Adhesive intestinal obstruction in laparoscopic vs open colorectal resection.
AB  - AIM: While there is evidence that laparoscopy creates fewer adhesions, evidence
      regarding decreased episodes of adhesive obstruction in laparoscopic colorectal
      resection (LCR) is still lacking. The aim of our study was to compare the
      incidence of adhesion-related admissions/surgery in patients undergoing LCR and
      open colorectal resection (OCR). METHOD: We conducted a retrospective analysis of
      a prospectively collected database that included all patients undergoing LCR and
      OCR between 2001 and 2010. Patients with <6 months of follow-up were excluded.
      Patients who were converted to open surgery were included in the laparoscopic
      group. Details regarding readmission rates and surgery for adhesive obstruction
      were obtained from clinical portals and the theatre database. Statistical
      analysis was performed using Fisher's exact test, the Mann-Whitney U-test and the
      Student's t-test. RESULTS: One-hundred and forty-four patients had LCR with a
      median (range) follow-up of 24.5 (6-108) months. One-hundred and eighty-seven
      patients underwent OCR, with a median (range) follow-up of 49 (6-104) months. Six
      (4.2%) of 144 patients in the LCR group had adhesion-related
      admission/obstruction compared with 13 (6.95%) of 187 patients in the OCR group
      (P = 0.34). Three (2.1%) of 144 patients who had LCR required surgery for
      adhesive obstruction compared with five (2.7%) of 187 who had OCR (P = 0.73).
      CONCLUSION: In our study there was no statistically significant difference in the
      incidence of postoperative adhesive intestinal obstruction between LCR and OCR
      groups.

PMID- 22607207
TI  - An examination of some safety issues among commercial motorcyclists in Nigeria: a
      case study.
AB  - The reduction of road crashes and injuries among motorcyclists in Nigeria
      requires a system inquiry into some safety issues at pre-crash, crash and post
      crash stages to guide action plans. This paper examines safety issues such as age
      restriction, motorcycle engine capacity, highway code awareness, licence holding,
      helmet usage, crash involvement, rescue and payment for treatment among
      commercial motorcyclists. The primary data derived from a structured
      questionnaire administered to 334 commercial motorcyclists in Samaru, Zaria were
      analysed using descriptive statistics and logistic regression technique. There
      was total compliance with age restriction and motorcycle engine capacity. About
      41.8% of the operators were not aware of the existence of the highway code. The
      odds of licence holding increased with highway code awareness, education with
      above senior secondary as the reference category and earnings. The odds of crash
      involvement decreased with highway code awareness, earnings and mode of
      operation. About 84% of the motorcyclists did not use crash helmet, in spite of
      being aware of the benefit, and 65.4% of motorcycle crashes was found to be with
      other road users. The promotion of safety among motorcyclists therefore requires
      strict traffic law enforcement and modification of road design to segregate
      traffic and protect pedestrians.

PMID- 22607208
TI  - Glutathionylation of cytosolic glyceraldehyde-3-phosphate dehydrogenase from the
      model plant Arabidopsis thaliana is reversed by both glutaredoxins and
      thioredoxins in vitro.
AB  - Plants contain both cytosolic and chloroplastic GAPDHs (glyceraldehyde-3
      phosphate dehydrogenases). In Arabidopsis thaliana, cytosolic GAPDH is involved
      in the glycolytic pathway and is represented by two differentially expressed
      isoforms (GapC1 and GapC2) that are 98% identical in amino acid sequence. In the
      present study we show that GapC1 is a phosphorylating NAD-specific GAPDH with
      enzymatic activity strictly dependent on Cys(149). Catalytic Cys(149) is the only
      solvent-exposed cysteine of the protein and its thiol is relatively acidic
      (pK(a)=5.7). This property makes GapC1 sensitive to oxidation by H(2)O(2), which
      appears to inhibit enzyme activity by converting the thiolate of Cys(149) (-S-)
      into irreversible oxidized forms (-SO(2)(-) and -SO(3)(-)) via a labile sulfenate
      intermediate (-SO(-)). GSH (reduced glutathione) prevents this irreversible
      process by reacting with Cys(149) sulfenates to give rise to a mixed disulfide
      (Cys(149)-SSG), as demonstrated by both MS and biotinylated GSH. Glutathionylated
      GapC1 can be fully reactivated either by cytosolic glutaredoxin, via a GSH
      dependent monothiol mechanism, or, less efficiently, by cytosolic thioredoxins
      physiologically reduced by NADPH:thioredoxin reductase. The potential relevance
      of these findings is discussed in the light of the multiple functions of GAPDH in
      eukaryotic cells (e.g. glycolysis, control of gene expression and apoptosis) that
      appear to be influenced by the redox state of the catalytic Cys(149).

PMID- 22607209
TI  - Profile-based short linear protein motif discovery.
AB  - BACKGROUND: Short linear protein motifs are attracting increasing attention as
      functionally independent sites, typically 3-10 amino acids in length that are
      enriched in disordered regions of proteins. Multiple methods have recently been
      proposed to discover over-represented motifs within a set of proteins based on
      simple regular expressions. Here, we extend these approaches to profile-based
      methods, which provide a richer motif representation. RESULTS: The profile motif
      discovery method MEME performed relatively poorly for motifs in disordered
      regions of proteins. However, when we applied evolutionary weighting to account
      for redundancy amongst homologous proteins, and masked out poorly conserved
      regions of disordered proteins, the performance of MEME is equivalent to that of
      regular expression methods. However, the two approaches returned different
      subsets within both a benchmark dataset, and a more realistic discovery dataset.
      CONCLUSIONS: Profile-based motif discovery methods complement regular expression
      based methods. Whilst profile-based methods are computationally more intensive,
      they are likely to discover motifs currently overlooked by regular expression
      methods.

PMID- 22607211
TI  - Dialysis medical directors' role in maintaining quality of care and
      responsibility for facility-specific patient outcomes: evolution and current
      status.

PMID- 22607210
TI  - The impact of click chemistry in medicinal chemistry.
AB  - INTRODUCTION: The copper(I)-catalyzed 1,3-dipolar cycloaddition of alkynes and
      azides to form 1,2,3-triazoles is the most popular reaction in click chemistry.
      This reaction is also near-perfect, in terms of its robustness, due to the high
      degree of reliability and complete specificity. Furthermore, this reaction has
      been used increasingly in drug discovery, because the formed 1,2,3-triazole can
      act as both a bioisostere and a linker. AREAS COVERED: This review provides an
      overview of a most important click reaction, 1,3-dipolar cycloadditions of
      alkynes and azides, in the drug discovery. EXPERT OPINION: Click chemistry is a
      very powerful tool, in the drug discovery, because it is very efficient in the
      creation of compound libraries through combinatorial methodology. However, the
      1,2,3-triazole ring itself is not a commonly used pharmacophore and has rarely
      been found in marketed drugs, demonstrating that there are still some limitations
      during the use of 1,2,3-triazole in the molecules of drug candidates. Hopefully,
      in the next decade, we will witness the emergence of 1,2,3-triazole-bearing drugs
      on the market as this click reaction is used more and more widely in the drug
      discovery.

PMID- 22607212
TI  - Treatment center characteristics associated with better outcomes: a role for the
      medical director?

PMID- 22607213
TI  - Intensity of care and better outcomes among hemodialysis patients: a role for the
      Medical Director.
AB  - The Medical Director is responsible for all levels of quality patient care in the
      facility as mandated by the 2008 revision of the Medicare Conditions for Coverage
      of dialysis facilities. He/she is the leader and primary individual tasked with
      ensuring that facility processes are in place to meet or exceed key quality goals
      or adopt new ones and prioritize them appropriately-all to drive improved
      facility performance, particularly the ultimate outcomes of morbidity and
      mortality rates. Management of vascular access, dialysis dose, mineral
      metabolism, acid-base balance, sodium and fluid management, anemia, among other
      aspects of care, have representative intermediate clinical outcomes that are
      often called "surrogate" or "process" measures-because they may reflect the
      quality of care delivery while impacting "primary" outcomes such as death and
      hospitalization. The proportion of dialysis patients within a dialysis facility
      meeting a selected group among these goals has become the standard "care process"
      metric since the 1990s. Evidence supports its use, in that graded improvements in
      the facility patients' primary outcomes have been documented as more patients in
      a facility achieved a greater number of these "process" goals. A caveat: these
      process measures do not represent overall quality by themselves because
      nonclinical processes also influence primary outcomes. Nevertheless, process
      improvement in meeting facility goals should be led by the Medical Director,
      particularly those with the strongest links to primary outcomes such as reduction
      of hemodialysis catheter exposure, forming the cornerstone of quality improvement
      efforts. Specific recommendations on how to effectively lead a care team to
      achieve these goals are discussed.

PMID- 22607214
TI  - Clinical utility of natriuretic peptides in dialysis patients.
AB  - Dialysis patients suffer a greatly heightened risk of cardiovascular morbidity
      and mortality. These patients also experience an extremely high prevalence of
      left ventricular hypertrophy, heart failure, and coronary artery disease. Thus,
      there is a clinical need to identify circulating biomarkers that have diagnostic
      value for cardiovascular disease and have prognostic importance so to facilitate
      earlier and more aggressive intervention. The natriuretic peptides, namely brain
      natriuretic peptide (BNP) or N-terminal pro-brain natriuretic peptide (NT-pro
      BNP), belong to a family of vasopeptide hormones that are released from the heart
      and play a major role in blood pressure regulation and volume homeostasis through
      their direct effects on the kidney and systemic vasculature and represent a
      favorable aspect of neurohumoral activation. Testing for BNP or NT-pro-BNP has
      recently emerged as important diagnostic tool for heart failure and a useful
      biomarker for risk stratification in the general population. In dialysis
      patients, there has been interest in evaluating the potential of BNP and NT-pro
      BNP as markers of volume status as they are frequently elevated in dialysis
      patients. However, the interpretation of their levels is confounded by impaired
      renal clearance and preexisting LV abnormalities which have limited their
      applicability as a surrogate marker of volume status. In this article, we discuss
      the pathophysiology accounting for the elevation of natriuretic peptides in
      dialysis patients and review current evidence that supports their clinical
      utility as a diagnostic and prognostic tool in this population.

PMID- 22607215
TI  - Fat-soluble vitamins in advanced CKD/ESKD: a review.
AB  - Patients requiring dialysis often experience a significant decline in their
      nutritional status through a combination of chronic disease, reduced appetite,
      and dietary restrictions, which places them at risk for vitamin deficiencies. The
      concept of vitamin deficiency has evolved from obvious deficiency states to the
      subtle effects that suboptimal intake may have on chronic disease prevalence or
      progression. The purpose of this study was to summarize the current state of
      knowledge regarding the status of the fat-soluble vitamins (A, D, E, and K) in
      patients with chronic kidney disease receiving hemodialysis.

PMID- 22607217
TI  - Enhancing attributional style as a resiliency factor in depressogenic stress
      generation.
AB  - There is a growing body of evidence that suggests depression and cognitive
      vulnerabilities to depression may lead individuals to generate stressful events.
      However, there has been no study to date that has directly examined factors that
      may lead individuals to be less likely to generate stressful events. The present
      study examines whether an enhancing attributional style, the tendency to make
      global and stable inferences following occurrence of a positive event, functions
      as a resiliency factor in stress generation. One hundred and sixty-seven female
      students completed measures of depression symptoms and attributional style at
      baseline and occurrence of life events since baseline at a four-week follow-up.
      Results indicated that an enhancing attributional style predicted decreased
      levels of stressful events over the following four weeks, even when controlling
      for depression symptoms. The findings of this study suggest that there may be
      resiliency factors that can help protect individuals from the generation of
      stressful events.

PMID- 22607218
TI  - Predictors of trips to food destinations.
AB  - BACKGROUND: Food environment studies have focused on ethnic and income
      disparities in food access. Few studies have investigated distance travelled for
      food and did not aim to inform the geographic scales at which to study the
      relationship between food environments and obesity. Further, studies have not
      considered neighborhood design as a predictor of food purchasing behavior.
      METHODS: Atlanta residents (N = 4800) who completed a travel diary and reported
      purchasing or consuming food at one of five food locations were included in the
      analyses. A total of 11,995 food-related trips were reported. Using mixed
      modeling to adjust for clustering of trips by participants and households, person
      level variables (e.g. demographics), neighborhood-level urban form measures,
      created in GIS, and trip characteristics (e.g. time of day, origin and
      destination) were investigated as correlates of distance travelled for food and
      frequency of grocery store and fast food outlet trips. RESULTS: Mean travel
      distance for food ranged from 4.5 miles for coffee shops to 6.3 miles for
      superstores. Type of store, urban form, type of tour, day of the week and
      ethnicity were all significantly related to distance travelled for food. Origin
      and destination environment, type of tour, day of week, age, gender, income,
      ethnicity, vehicle access and obesity status were all significantly related to
      visiting a grocery store. Home neighborhood environment, day of week, type of
      tour, gender, income, education level, age, and obesity status were all
      significantly related to likelihood of visiting a fastfood outlet. CONCLUSIONS:
      The present study demonstrated that people travel sizeable distances for food and
      this distance is related to urban. Results suggest that researchers need to
      employ different methods to characterize food environments than have been used to
      assess urban form in studies of physical activity. Food is most often purchased
      while traveling from locations other than home, so future studies should assess
      the food environment around work, school or other frequently visited
      destinations, as well as along frequently traveled routes.

PMID- 22607219
TI  - Multiple binding modes of inhibitors to carbonic anhydrases: how to design
      specific drugs targeting 15 different isoforms?

PMID- 22607220
TI  - Importance of having low-density functional groups for generating high
      performance semiconducting polymer dots.
AB  - Semiconducting polymers with low-density side-chain carboxylic acid groups were
      synthesized to form stable, functionalized, and highly fluorescent polymer dots
      (Pdots). The influence of the molar fraction of hydrophilic side-chains on Pdot
      properties and performance was systematically investigated. Our results show that
      the density of side-chain carboxylic acid groups significantly affects Pdot
      stability, internal structure, fluorescence brightness, and nonspecific binding
      in cellular labeling. Fluorescence spectroscopy, single-particle imaging, and a
      dye-doping method were employed to investigate the fluorescence brightness and
      the internal structure of the Pdots. The results of these experiments indicate
      that semiconducting polymers with low density of side-chain functional groups can
      form stable, compact, and highly bright Pdots as compared to those with high
      density of hydrophilic side-chains. The functionalized polymer dots were
      conjugated to streptavidin (SA) by carbodiimide-catalyzed coupling and the Pdot
      SA probes effectively and specifically labeled the cancer cell-surface marker
      Her2 in human breast cancer cells. The carboxylate-functionalized polymer could
      also be covalently modified with small functional molecules to generate Pdot
      probes for click chemistry-based bio-orthogonal labeling. This study presents a
      promising approach for further developing functional Pdot probes for biological
      applications.

PMID- 22607221
TI  - Validation of the Verbal and Social Interaction questionnaire: carers' focus in
      the carer-resident relationship in supported housing facilities for persons with
      psychiatric disabilities (VSI-SH).
AB  - A questionnaire to measure the verbal and social interactions between carers and
      residents in supported housing facilities for persons with psychiatric
      disabilities has been developed. It is an adaptation of a questionnaire
      originally used in a forensic psychiatric setting. The aim of the present study
      was thus to investigate the construct validity and the reliability of this new
      version of the Verbal and Social Interactions questionnaire for use in supported
      housing facilities (VSI-SH). Two hundred and twenty-three carers from municipal
      and privately run housing facilities completed the questionnaire. A factor
      analysis was performed, which resulted in six factors. The number of items was
      reduced from the original 47 to 30 in order to minimize factorial complexity and
      multiple loadings. The reliability was tested with Cronbach's alpha and good
      internal consistency for the questionnaire and five of the six factors was found.
      The resulting six factors and the items were compared to the conceptual model and
      four of the six factors corresponded well with the categories in this original
      theoretical model. The questionnaire can be a useful contribution to the study of
      interactions between carers and residents in supported housing facilities for
      persons with psychiatric disabilities.

PMID- 22607222
TI  - Minimally invasive decompression and stabilization for the management of
      thoracolumbar spine metastasis.
AB  - OBJECT: Spinal metastasis with spinal cord involvement is a frequent complication
      in cancer patients. As the spinal compression frequently occurs ventrally,
      performing a simple posterior laminectomy alone is generally ineffective and
      dangerous. Many aggressive surgical strategies have been developed to improve
      outcomes for patients with metastatic spine disease. These strategies are
      associated with high morbidity and complication rates, especially in patients
      with numerous neoplasm-associated comorbidities, which can limit their indication
      in patients with a limited life expectancy. The authors performed a prospective
      evaluation of minimally invasive decompression and stabilization for the
      palliative management of symptomatic thoracolumbar spine metastasis. METHODS: Ten
      patients with metastasis to the thoracolumbar spine and neurological compromise
      underwent minimally invasive transpedicular vertebrectomy and spinal cord
      decompression through a tubular expandable retractor. Percutaneous stabilization
      was also systematically performed to ensure spinal stability. RESULTS: No
      complications during the procedure were reported. The mean operative duration was
      170 minutes and the mean estimated blood loss was 400 ml. The postoperative
      course of all patients was uneventful, with the exception of 1 benign urinary
      tract infection. Eight patients (80%) improved at least 1 Frankel grade.
      CONCLUSIONS: Minimally invasive treatment of thoracolumbar spine metastasis is a
      safe and effective palliative option in patients with limited life expectancy, to
      limit morbidity and preserve quality of life.

PMID- 22607223
TI  - Implications of the center of rotation concept for the reconstruction of anterior
      column lordosis and axial preloads in spinal deformity surgery.
AB  - OBJECT: In thoracolumbar deformity surgery, anterior-only approaches are used for
      reconstruction of anterior column failures. It is generally advised that
      vertebral body replacements (VBRs) should be preloaded by compression. However,
      little is known regarding the impact of different techniques for generation of
      preloads and which surgical principle is best for restoration of lordosis.
      Therefore, the authors analyzed the effect of different surgical techniques to
      restore spinal alignment and lordosis as well as the ability to generate axial
      preloads on VBRs in anterior column reconstructions. METHODS: The authors
      performed a laboratory study using 7 fresh-frozen specimens (from T-3 to S-1) to
      assess the ability for lordosis reconstruction of 5 techniques and their
      potential for increasing preloads on a modified distractable VBR in a 1-level
      thoracolumbar corpectomy. The testing protocol was as follows: 1) Radiographs of
      specimens were obtained. 2) A 1-level corpectomy was performed. 3) In alternating
      order, lordosis was applied using 1 of the 5 techniques. Then, preloads during
      insertion and after relaxation using the modified distractable VBR were assessed
      using a miniature load-cell incorporated in the modified distractable VBR. The
      modified distractable VBR was inserted into the corpectomy defect after lordosis
      was applied using 1) a lamina spreader; 2) the modified distractable VBR only; 3)
      the ArcoFix System (an angular stable plate system enabling in situ reduction);
      4) a lordosizer (a customized instrument enabling reduction while replicating the
      intervertebral center of rotation [COR] according to the COR method); and 5) a
      lordosizer and top-loading screws ([LZ+TLS], distraction with the lordosizer
      applied on a 5.5-mm rod linked to 2 top-loading pedicle screws inserted laterally
      into the vertebra). Changes in the regional kyphosis angle were assessed
      radiographically using the Cobb method. RESULTS: The bone mineral density of
      specimens was 0.72 +/- 22.6 g/cm(2). The maximum regional kyphosis angle
      reconstructed among the 5 techniques averaged 9.7 degrees -16.1 degrees , and
      maximum axial preloads averaged 123.7-179.7 N. Concerning correction, in
      decreasing order the LZ+TLS, lordosizer, and ArcoFix System outperformed the
      lamina spreader and modified distractable VBR. The order of median values for
      insertion peak load, from highest to lowest, were lordosizer, LZ+TLS, and
      ArcoFix, which outperformed the lamina spreader and modified distractable VBR. In
      decreasing order, the axial preload was highest with the lordosizer and LZ+TLS,
      which both outperformed the lamina spreader and the modified distractable VBR.
      The technique enabling the greatest lordosis achieved the highest preloads. With
      the ArcoFix System and LZ+TLS, compression loads could be applied and were 247.8
      and 190.6 N, respectively, which is significantly higher than the insertion peak
      load and axial preload (p < 0.05). CONCLUSIONS: Including the ability for
      replication of the COR in instruments designed for anterior column
      reconstructions, the ability for lordosis restoration of the anterior column and
      axial preloads can increase, which in turn might foster fusion.

PMID- 22607225
TI  - Low incidence of bleeding-related morbidity with left ventricular assist device
      implantation in the current era.
AB  - Left ventricular assist device (LVAD) implantation is historically associated
      with high incidence of bleeding-related complications, very high reexploration
      rates, and frequently massive blood transfusion. Bleeding predisposes to
      mortality, sepsis, allosensitization, and right ventricular failure. We present
      results of an integrated approach to reduce bleeding complications. Analysis of
      51 implantable LVADs implanted in 50 patients (mean age 52 years; male, 45;
      Intragency Registry for Mechanically Assisted Circulatory Support [INTERMACS] 1
      or 2, 25) in our center in 2008 and 2009, including 15 reoperations. Preoperative
      coagulopathy was evident in 10 patients. Our strategy included: early LVAD
      implantation, preoperative nutritional support and hemodynamic optimization,
      preferential use of continuous flow LVADs, meticulous surgical hemostasis,
      liberal application of tricuspid annuloplasty, and blood product utilization
      based on point-of-care testing. Two patients (4%) were reexplored for bleeding.
      Median transfusion rates intraoperatively were: blood: 2 units (interquartile
      range [IQR] 0-4); plasma: 0 units (0-2.75); platelets: 0 pools (0-1.75), while
      postoperative transfusion rates for first 48 h were blood: 1 unit (0-2); plasma:
      0 units (0-0.75); and platelets: 0 pools (0,1). Right ventricular assist device
      was utilized in six patients (11%). Median chest tube drainage in first 24 h was
      1230 mL (IQR 862-1687). Median time on ventilator was 2 days, intensive care unit
      was 6 days, and hospitalization was 18 days. Hospital mortality was 20%. Using an
      integrated approach, we have experienced bleeding and transfusion rates similar
      to that seen in non-LVAD complex cardiac operations. The potential to reduce
      bleeding reduces invasiveness of LVAD surgery, reduces allosensitization, may
      improve outcomes, and may increase mainstream acceptability of LVADs as
      definitive therapy for heart failure.

PMID- 22607224
TI  - Tweaking the cholesterol efflux capacity of reconstituted HDL.
AB  - Mechanisms to increase plasma high-density lipoprotein (HDL) or to promote egress
      of cholesterol from cholesterol-loaded cells (e.g., foam cells from
      atherosclerotic lesions) remain an important target to regress heart disease.
      Reconstituted HDL (rHDL) serves as a valuable vehicle to promote cellular
      cholesterol efflux in vitro and in vivo. rHDL were prepared with wild type
      apolipoprotein (apo) A-I and the rare variant, apoA-I Milano (M), and each
      apolipoprotein was reconstituted with phosphatidylcholine (PC) or sphingomyelin
      (SM). The four distinct rHDL generated were incubated with CHO cells, J774
      macrophages, and BHK cells in cellular cholesterol efflux assays. In each cell
      type, apoA-I(M) SM-rHDL promoted the greatest cholesterol efflux. In BHK cells,
      the cholesterol efflux capacities of all four distinct rHDL were greatly enhanced
      by increased expression of ABCG1. Efflux to PC-containing rHDL was stimulated by
      transfection of a nonfunctional ABCA1 mutant (W590S), suggesting that binding to
      ABCA1 represents a competing interaction. This interpretation was confirmed by
      binding experiments. The data show that cholesterol efflux activity is dependent
      upon the apoA-I protein employed, as well as the phospholipid constituent of the
      rHDL. Future studies designed to optimize the efflux capacity of therapeutic rHDL
      may improve the value of this emerging intervention strategy.

PMID- 22607226
TI  - Prescribing without evidence - pregnancy.
AB  - Prescribing of medicines during pregnancy is common, and for some groups of women
      is essential for maintaining maternal and therefore fetal health. Pregnant women
      and prescribers are rightly concerned, however, about the potential adverse fetal
      effects of medicines. These may include fetal death or stillbirth, congenital
      malformations, developmental impairment, neonatal effects or late carcinogenesis.
      It is therefore essential that the risks and benefits for mother and fetus are
      considered carefully before prescribing in pregnancy. This is often challenging
      because of the paucity of information available. To complicate the issue further,
      drug pharmacokinetics are commonly altered in pregnancy, potentially affecting
      optimal dosing as well as interpretation of plasma concentration measurements,
      with specific information on individual drugs seldom available. Most drugs cross
      the placenta, especially lipophilic drugs and those with low plasma protein
      binding. Active membrane transporters also have an important role in enhancing or
      preventing drug transfer, although this is not yet clearly understood. Animal
      studies have limited applicability to humans because of species-specific effects,
      and clinical trials in pregnancy are only undertaken in special circumstances.
      Prescribers therefore need to rely on observational studies of fetal outcomes
      following drug exposure in human pregnancy. These often involve limited numbers,
      and data are also subject to confounding and bias, making interpretation
      difficult. It therefore remains essential that appropriate mechanisms for
      systematic data collection, including congenital malformation registries,
      teratology information services, pregnancy registers and linked population
      registries, are maintained and enhanced to increase the amount and quality of
      information available.

PMID- 22607227
TI  - Integrated mosquito larval source management reduces larval numbers in two
      highland villages in western Kenya.
AB  - BACKGROUND: In western Kenya, malaria remains one of the major health problems
      and its control remains an important public health measure. Malaria control is by
      either use of drugs to treat patients infected with malaria parasites or by
      controlling the vectors. Vector control may target the free living adult or
      aquatic (larval) stages of mosquito. The most commonly applied control strategies
      target indoor resting mosquitoes. However, because mosquitoes spend a
      considerable time in water, targeting the aquatic stages can complement well with
      existing adult control measures. METHODS: Larval source management (LSM) of
      malaria vectors was examined in two villages i.e. Fort Ternan and Lunyerere, with
      the aim of testing strategies that can easily be accessed by the affected
      communities. Intervention strategies applied include environmental management
      through source reduction (drainage of canals, land levelling or by filling
      ditches with soil), habitat manipulation (by provision of shading from arrow root
      plant), application of Bacillus thuringiensis var israelensis (Bti) and the use
      of predatory fish, Gambusia affinis. The abundance of immature stages of
      Anopheles and Culex within intervention habitats was compared to that within non
      intervention habitats. RESULTS: The findings show that in Fort Ternan no
      significant differences were observed in the abundance of Anopheles early and
      late instars between intervention and non-intervention habitats. In Lunyerere,
      the abundance of Anopheles early instars was fifty five times more likely to be
      present within non-intervention habitats than in habitats under drainage. No
      differences in early instars abundance were observed between non-intervention and
      habitats applied with Bti. However, late instars had 89 % and 91 % chance of
      being sampled from non-intervention rather than habitats under drainage and those
      applied with Bti respectively. CONCLUSION: Most of these interventions were
      applied in habitats that arose due to human activities. Involvement of community
      members in control programs would be beneficial in the long term once they
      understand the role they play in malaria transmission. Apart from the need for
      communities to be educated on their role in malaria transmission, there is a need
      to develop and test strategies that can easily be accessed and hence be used by
      the affected communities. The proposed LSM strategies target outdoor immature
      mosquitoes and hence can complement well with control measures that target indoor
      resting vectors. Therefore inclusion of LSM in Integrated Vector Management (IVM)
      program would be beneficial.

PMID- 22607228
TI  - Invasion facilitates hybridization with introgression in the Rattus rattus
      species complex.
AB  - Biological invasions result in novel species interactions, which can have
      significant evolutionary impacts on both native and invading taxa. One
      evolutionary concern with invasions is hybridization among lineages that were
      previously isolated, but make secondary contact in their invaded range(s). Black
      rats, consisting of several morphologically very similar but genetically distinct
      taxa that collectively have invaded six continents, are arguably the most
      successful mammalian invaders on the planet. We used mitochondrial cytochrome b
      sequences, two nuclear gene sequences (Atp5a1 and DHFR) and nine microsatellite
      loci to examine the distribution of three invasive black rat lineages (Rattus
      tanezumi, Rattus rattus I and R. rattus IV) in the United States and Asia and to
      determine the extent of hybridization among these taxa. Our analyses revealed two
      mitochondrial lineages that have spread to multiple continents, including a
      previously undiscovered population of R. tanezumi in the south-eastern United
      States, whereas the third lineage (R. rattus IV) appears to be confined to
      Southeast Asia. Analyses of nuclear DNA (both sequences and microsatellites)
      suggested significant hybridization is occurring among R. tanezumi and R. rattus
      I in the United States and also suggest hybridization between R. tanezumi and R.
      rattus IV in Asia, although further sampling of the latter species pair in Asia
      is required. Furthermore, microsatellite analyses suggest unidirectional
      introgression from both R. rattus I and R. rattus IV into R. tanezumi. Within the
      United States, introgression appears to be occurring to such a pronounced extent
      that we were unable to detect any nuclear genetic signal for R. tanezumi, and a
      similar pattern was detected in Asia.

PMID- 22607229
TI  - Overexpression of an exotic thermotolerant beta-glucosidase in trichoderma reesei
      and its significant increase in cellulolytic activity and saccharification of
      barley straw.
AB  - BACKGROUND: Trichoderma reesei is a widely used industrial strain for cellulase
      production, but its low yield of beta-glucosidase has prevented its industrial
      value. In the hydrolysis process of cellulolytic residues by T. reesei, a
      disaccharide known as cellobiose is produced and accumulates, which inhibits
      further cellulases production. This problem can be solved by adding beta
      glucosidase, which hydrolyzes cellobiose to glucose for fermentation. It is,
      therefore, of high vvalue to construct T. reesei strains which can produce
      sufficient beta-glucosidase and other hydrolytic enzymes, especially when those
      enzymes are capable of tolerating extreme conditions such as high temperature and
      acidic or alkali pH. RESULTS: We successfully engineered a thermostable beta
      glucosidase gene from the fungus Periconia sp. into the genome of T. reesei
      QM9414 strain. The engineered T. reesei strain showed about 10.5-fold (23.9
      IU/mg) higher beta-glucosidase activity compared to the parent strain (2.2 IU/mg)
      after 24 h of incubation. The transformants also showed very high total cellulase
      activity (about 39.0 FPU/mg) at 24 h of incubation whereas the parent strain
      almost did not show any total cellulase activity at 24 h of incubation. The
      recombinant beta-glucosidase showed to be thermotolerant and remains fully active
      after two-hour incubation at temperatures as high as 60 degrees C. Additionally,
      it showed to be active at a wide pH range and maintains about 88% of its maximal
      activity after four-hour incubation at 25 degrees C in a pH range from 3.0 to
      9.0. Enzymatic hydrolysis assay using untreated, NaOH, or Organosolv pretreated
      barley straw as well as microcrystalline cellulose showed that the transformed T.
      reesei strains released more reducing sugars compared to the parental strain.
      CONCLUSIONS: The recombinant T. reesei overexpressing Periconia sp. beta
      glucosidase in this study showed higher beta-glucosidase and total cellulase
      activities within a shorter incubation time (24 h) as well as higher hydrolysis
      activity using biomass residues. These features suggest that the transformants
      can be used for beta-glucosidase production as well as improving the biomass
      conversion using cellulases.

PMID- 22607230
TI  - Chromatographic separation of reaction products from the choline
      acetyltransferase and carnitine acetyltransferase assay: differential ChAT and
      CrAT activity in brain extracts from Alzheimer's disease versus controls.
AB  - Choline acetyltransferase (ChAT) catalyzes the reaction between choline and
      acetylcoenzyme A (AcCoA) to form acetylcholine (ACh) in nerve terminals. ACh
      metabolism has implications in numerous aspects of physiology and varied disease
      states, such as Alzheimer's disease. Therefore a specific, sensitive, and
      reliable method for detecting ChAT enzyme activity is of great utility in a
      number of situations. Using an existing radionuclide-based enzyme activity assay,
      we have observed detectable ChAT signals from non-cholinergic cells, suggesting a
      contaminant in the assay producing an artifactual signal. Previous reports have
      suggested that L-acetylcarnitine (LAC) contaminates many assays of ChAT activity,
      because of difficulties in separating LAC from ACh by organic extraction. To
      determine the source of this hypothesized artifact and to rectify the problem, we
      have developed a paper chromatography-based assay for the detection of
      acetylcholine and other contaminating reaction products of this assay, including
      LAC. Our first goal was to develop a simple and economical method for resolving
      and verifying the identities of various reaction products or contaminants that
      could be performed in most laboratories without specialized equipment. Our second
      goal was to apply this separation method in postmortem human brain tissue
      samples. Our assay successfully detected several contaminants, especially in
      assays using brain tissue, and allowed the separation of the intended ACh product
      from these contaminants. We further demonstrate that this assay can be used to
      measure carnitine acetyltransferase (CrAT) activity in the same samples, and
      assays comparing ChAT and CrAT show that CrAT is highly active in neuronal
      tissues and in neuronal cell cultures relative to ChAT. Thus, the simple
      chromatography-based assay we describe allows the measurement of specific
      reaction products separated from contaminants using commonly available and
      inexpensive materials. Further, we show that ChAT activity is significantly
      reduced in brain extracts from Alzheimer's disease compared to controls.

PMID- 22607232
TI  - Aortic rupture and aorto-pulmonary fistulation in the Friesian horse:
      characterisation of the clinical and gross post mortem findings in 24 cases.
AB  - REASONS FOR PERFORMING STUDY: In horses, aortic sinus of Valsalva aneurysms or
      tears in the aortic root are well-recognised conditions in breeding stallions,
      often leading to sudden death. A more uncommon form of aortic rupture, located
      proximal to the ligamentum arteriosum has been reported in 3 Friesian horses.
      OBJECTIVES: The purpose of this study was to phenotypically characterise aortic
      rupture and aorto-pulmonary fistulation in Friesian horses in terms of clinical
      and post mortem data based on 24 cases. METHODS: Friesian horses that were
      diagnosed with aortic rupture and aorto-pulmonary fistulation over a period of 13
      years (1997-2010) at the Department of Equine Sciences of Utrecht University (n =
      15) and Wolvega Equine Hospital (n = 9), were included in this study. Case
      history, results of clinical examination and gross post mortem findings were
      screened and analysed. RESULTS: Some cases were found dead without prior
      symptoms, but in several cases signs such as recurrent colic, peripheral oedema
      and sustained tachycardia were present for several weeks prior to cardiac
      failure. Clinical examination during hospitalisation revealed increased rectal
      temperature, peripheral oedema and increased jugular pulse with a bounding
      arterial pulse. In the majority of horses an aortic rupture of the aortic arch
      near the ligamentum arteriosum, concurrent with a circumferential cuff of
      perivascular haemorrhage and aorto-pulmonary fistulation, was found at post
      mortem examination. CONCLUSIONS: Aorto-pulmonary fistulation in conjunction with
      aortic rupture is more common in Friesians than previously estimated. In some
      cases findings demonstrate a progressive pathology rather than acute cardiac
      failure and sudden death. An appropriate approach is necessary during post mortem
      examination of the heart in order not to overlook the diagnosis. POTENTIAL
      RELEVANCE: Equine practitioners should realise that in Friesian horses presented
      with a history of recurrent false colic, coughing, sustained tachycardia and/or
      peripheral oedema, aortic rupture and aorto-pulmonary fistulation should be
      included in the differential diagnosis.

PMID- 22607231
TI  - Natural product-derived antitumor compound phenethyl isothiocyanate inhibits
      mTORC1 activity via TSC2.
AB  - Phenethyl isothiocyanate (1) is a natural dietary phytochemical with cytostatic,
      cytotoxic, and antitumor activity. The effects of 1 were investigated on the
      activity of mTOR, a kinase that enhances the translation of many RNAs encoding
      proteins critical for cancer cell growth, including the angiogenesis regulator
      HIF1alpha. Compound 1 effectively blocked HIF1alpha RNA translation in MCF7
      breast cancer cells, and this was associated with reduced phosphorylation of 4E
      BP1 and p70 S6K, well-characterized downstream substrates of the mTOR-containing
      mTORC1 complex. Compound 1 also inhibited mTORC1 activity in mouse embryonic
      fibroblasts (MEFs). The 1-mediated inhibition of mTORC1 activity appeared to be
      independent of the upstream regulators PTEN, AKT, ERK1/2, and AMPK. By contrast,
      1-mediated inhibition of mTORC1 activity was dependent on the presence of TSC2,
      part of a complex that regulates mTORC1 activity negatively. TSC2-deficient MEFs
      were resistant to 1-mediated inhibition of p70 S6K phosphorylation. TSC2
      deficient MEFs were also partially resistant to 1-mediated growth inhibition.
      Overall, the present results confirm that 1 inhibits mTORC1 activity. This is
      dependent on the presence of TSC2, and inhibition of mTORC1 contributes to
      optimal 1-induced growth inhibition. Inhibition of RNA translation may be an
      important component of the antitumor effects of phenethyl isothiocyanate.

PMID- 22607233
TI  - A pivotal registration phase III, multicenter, randomized tuberculosis controlled
      trial: design issues and lessons learnt from the Gatifloxacin for TB (OFLOTUB)
      project.
AB  - BACKGROUND: There have been no major advances in tuberculosis (TB) drug
      development since the first East African/British Medical Research Council short
      course chemotherapy trial 35 years ago. Since then, the landscape for conducting
      TB clinical trials has profoundly changed with the emergence of HIV infection,
      the spread of resistant TB bacilli strains, recent advances in
      mycobacteriological capacity, and drug discovery. As a consequence questions have
      arisen on the most appropriate approach to design and conduct current TB trials.
      To highlight key issues discussed: Is a superiority, equivalence, or non
      inferiority design most appropriate? What should be the primary efficacy outcome?
      How to consider re-infections in the definition of the outcome? What is the
      optimal length of patient follow-up? Is blinding appropriate when treatment
      duration in test arm is shorter? What are the appropriate assumptions for sample
      size calculation? METHODS: Various drugs are currently in the development
      pipeline. We are presenting in this paper the design of the most recently
      completed phase III TB trial, the OFLOTUB project, which is the pivotal trial of
      a registration portfolio for a gatifloxacin-containing TB regimen. It is a
      randomized, open-label, multicenter, controlled trial aiming to evaluate the
      efficacy and safety of a gatifloxacin-containing 4-month regimen (trial
      registration: ClinicalTrial.gov database: NCT00216385). RESULTS: In the light of
      the recent scientific and regulatory discussions, we discuss some of the design
      issues in TB clinical trials and more specifically the reasons that guided our
      choices, in order to best answer the trial objectives, while at the same time
      satisfying regulatory authority requirements. CONCLUSION: When shortening TB
      treatment, we are advocating for a non-inferiority, non-blinded design, with a
      composite unfavorable endpoint assessed 12 months post treatment completion, and
      added trial procedures specifically aiming to: (1) minimize endpoint
      unavailability; and (2) distinguish between relapse and re-infection.

PMID- 22607234
TI  - Multiple structure alignment with msTALI.
AB  - BACKGROUND: Multiple structure alignments have received increasing attention in
      recent years as an alternative to multiple sequence alignments. Although multiple
      structure alignment algorithms can potentially be applied to a number of
      problems, they have primarily been used for protein core identification. A method
      that is capable of solving a variety of problems using structure comparison is
      still absent. Here we introduce a program msTALI for aligning multiple protein
      structures. Our algorithm uses several informative features to guide its
      alignments: torsion angles, backbone Calpha atom positions, secondary structure,
      residue type, surface accessibility, and properties of nearby atoms. The
      algorithm allows the user to weight the types of information used to generate the
      alignment, which expands its utility to a wide variety of problems. RESULTS:
      msTALI exhibits competitive results on 824 families from the Homstrad and SABmark
      databases when compared to Matt and Mustang. We also demonstrate success at
      building a database of protein cores using 341 randomly selected CATH domains and
      highlight the contribution of msTALI compared to the CATH classifications.
      Finally, we present an example applying msTALI to the problem of detecting hinges
      in a protein undergoing rigid-body motion. CONCLUSIONS: msTALI is an effective
      algorithm for multiple structure alignment. In addition to its performance on
      standard comparison databases, it utilizes clear, informative features, allowing
      further customization for domain-specific applications. The C++ source code for
      msTALI is available for Linux on the web at http://ifestos.cse.sc.edu/mstali.

PMID- 22607235
TI  - OrganDots--an organotypic 3D tissue culture platform for drug development.
AB  - INTRODUCTION: There is an urgent need for preclinical testing systems that more
      accurately reflect responses in human target organs. The use of ex vivo tissues
      taken out of the human body and kept alive for sufficient time to perform testing
      has until recently been limited by tissue availability and by the length of time
      tissues can be kept alive outside the body, however, recent advances in tissue
      handling and tissue culture techniques have now made it possible to envisage
      using such tissues for drug discovery on a scale that is of value for the
      evaluation of compounds prior to testing in humans. AREAS COVERED: The article
      presents a method for generating 3D microtissues at the air-liquid interface
      'OrganDots' which are formed by reaggregating primary tissues or stem cell-based
      material which may be useful in drug discovery and development. The article
      compares this method with other methods for obtaining ex vivo tissues and looks
      at their uses as surrogates to testing compounds in humans. EXPERT OPINION:
      Reconstituting tissues in vitro has now reached a point where they can be used to
      profile the activity of compounds prior to in vivo testing. The ability to
      reconstitute tissues from primary material and the ability to synthesize new
      tissues in vitro from stem cells may lead to new testing systems that better
      reflect human pathophysiology and may allow individual differences to be
      expressed in vitro. These new drug testing systems should lead to more
      predictable in vitro drug testing systems in the near future.

PMID- 22607236
TI  - Influence of the casting technique and dynamic loading on screw detorque and
      misfit of single unit implant-supported prostheses.
AB  - OBJECTIVE: This study aimed to evaluate the influence of the casting procedure
      and cyclic loading of prosthetic frameworks on detorque of prosthetic screws and
      marginal misfit of single unit implant-supported prostheses. MATERIALS AND
      METHODS: Twenty specimens were obtained, each one consisting of a set of an
      implant (external hexagon 3.75 * 13 mm - Branemark type), a prosthetic abutment
      (entirely calcinable or overcasted UCLA) and a prosthetic screw. After the
      specimens were obtained, the prosthetic screws were tightened with 30 Ncm torque
      and released 24 h later in order to evaluate initial detorque. The screws were
      retightened and marginal gaps were assessed. All specimens were submitted to
      10(6) loading cycles, performed with 2 Hz frequency and 130 N load. The specimens
      were re-evaluated for marginal misfit and detorque after the mechanical loading
      (final marginal misfit/final detorque). The results were submitted to analysis of
      variance for repeated measurements, followed by Tukey HSD test (alpha = 0.05).
      RESULTS: No statistically significant differences were found on detorque values
      of the prosthetics screws for all groups and intervals evaluated (p = 0.8922).
      The entirely calcinable abutments showed higher initial marginal misfit compared
      to the overcasted ones (p = 0.0438). There was no statistically significant
      difference on marginal misfit before and after mechanical loading for both groups
      (p > 0.05). CONCLUSIONS: It can be concluded that the overcasted abutments showed
      lower misfit values when compared to the entirely casted abutments. No difference
      was observed on detorque values of prosthetic screws. After mechanical loading
      there was no difference on marginal misfit and detorque between the groups.

PMID- 22607237
TI  - Regulation of the electric charge in phosphatidic acid domains.
AB  - Although a minor component of the lipidome, phosphatidic acid (PA) plays a
      crucial role in nearly all signaling pathways involving cell membranes, in part
      because of its variable electrical charge in response to environmental
      conditions. To investigate how charge is regulated in domains of PA, we applied
      surface-sensitive X-ray reflectivity and fluorescence near-total-reflection
      techniques to determine the binding of divalent ions (Ca(2+) at various pH
      values) to 1,2-dimyristoyl-sn-glycero-3-phosphate (DMPA) and to the simpler lipid
      dihexadecyl phosphate (DHDP) spread as monolayers at the air/water interface. We
      found that the protonation state of PA is controlled not only by the pK(a) and
      local pH but also by the strong affinity to PA driven by electrostatic
      correlations from divalent ions and the cooperative effect of the two dissociable
      protons, which dramatically enhance the surface charge. A precise theoretical
      model is presented providing a general framework to predict the protonation state
      of PA. Implications for recent experiments on charge regulation by hydrogen
      bonding and the role of pH in PA signaling are discussed in detail.

PMID- 22607238
TI  - Blood transfusion in a developing society. Who is the best blood donor?

PMID- 22607240
TI  - Comparative transcriptomic analysis of streptococcus pseudopneumoniae with
      viridans group streptococci.
AB  - BACKGROUND: Streptococcus pseudopneumoniae, is a novel member of the genus
      Streptococcus, falling close to related members like S. pneumoniae, S. mitis, and
      S. oralis. Its recent appearance has shed light on streptococcal infections,
      which has been unclear till recently. In this study, the transcriptome of S.
      pseudopneumoniae CCUG 49455T was analyzed using the S. pneumoniae R6 microarray
      platform and compared with those of S. pneumoniae KCTC 5080T, S. mitis KCTC
      3556T, and S. oralis KCTC 13048T strains. RESULTS: Comparative transcriptome
      analysis revealed the extent of genetic relatedness among the species, and
      implies that S. pseudopneumoniae is the most closely related to S. pneumoniae. A
      total of 489, 444 and 470 genes were upregulated while 347, 484 and 443 were
      downregulated relative to S. pneumoniae in S. pseudopneumoniae, S. oralis and S.
      mitis respectively. Important findings were the up-regulation of TCS (two
      component systems) and transposase which were found to be specific to S.
      pseudopneumoniae. CONCLUSIONS: This study provides insight to the current
      understanding of the genomic content of S. pseudopneumoniae. The comparative
      transcriptome analysis showed hierarchical clustering of expression data of S.
      pseudopneumoniae with S. pneumoniae and S. mitis with S. oralis. This proves that
      transcriptional profiling can facilitate in elucidating the genetic distance
      between closely related strains.

PMID- 22607239
TI  - Allosteric modulation of caspase 3 through mutagenesis.
AB  - A mutation in the allosteric site of the caspase 3 dimer interface of Val266 to
      histidine abolishes activity of the enzyme, and models predict that the mutation
      mimics the action of small molecule allosteric inhibitors by preventing formation
      of the active site. Mutations were coupled to His266 at two sites in the
      interface, E124A and Y197C. We present results from X-ray crystallography,
      enzymatic activity and molecular dynamics simulations for seven proteins,
      consisting of single, double and triple mutants. The results demonstrate that
      considering allosteric inhibition of caspase 3 as a shift between discrete 'off
      state' or 'on-state' conformations is insufficient. Although His266 is
      accommodated in the interface, the structural defects are propagated to the
      active site through a helix on the protein surface. A more comprehensive view of
      allosteric regulation of caspase 3 requires the representation of an ensemble of
      inactive states and shows that subtle structural changes lead to the population
      of the inactive ensemble.

PMID- 22607241
TI  - Bioinspired oil strider floating at the oil/water interface supported by huge
      superoleophobic force.
AB  - Oil pollution to aquatic devices, especially to those oil-cleaning devices and
      equipment-repairing robots during oil spill accidents, has drawn great attention
      and remains an urgent problem to be resolved. Developing devices that can move
      freely in an oil/water system without contamination from oil has both scientific
      and practical importance. In nature, the insect water strider can float on water
      by utilizing the superhydrophobic supporting force received by its legs. Inspired
      by this unique floating phenomenon, in this article, we designed a model device
      named "oil strider" that could float stably at the oil/water interface without
      contamination by oil. The floating capability of the oil strider originated from
      the huge underwater superoleophobic supporting force its "legs" received. We
      prepared the micro/nanohierarchical structured copper-oxide-coated copper wires,
      acting as the artificial legs of oil strider, by a simple base-corrosion process.
      The surface structures and hydrophilic chemical components of the coatings on
      copper wires induced the huge superoleophobic force at the oil/water interface,
      to support the oil strider from sinking into the oil. Experimental results and
      theoretical analysis demonstrate that this supporting force is mainly composed of
      three parts: the buoyancy force, the curvature force, and the deformation force.
      We anticipate that this artificial oil strider will provide a guide for the
      design of smart aquatic devices that can move freely in an oil/water system with
      excellent oil repellent capability, and be helpful in practical situations such
      as oil handling and oil spill cleanup.

PMID- 22607242
TI  - Robot-assisted simple prostatectomy (RASP): does it make sense?
AB  - Study Type - Therapy (case series) Level of Evidence 4. What's known on the
      subject? and What does the study add? The open simple prostatectomy (OSP) is the
      'gold standard' for high-volume prostate adenomas. It shows very good functional
      results despite its invasiveness. Minimally invasive approaches, e.g. laparoscopy
      or holmium laser enucleation of the prostate, have been 'tested' but none have
      proved a substitute for the OSP. The robot-assisted approach provides optimal
      functional results and is easy to perform for experienced robotic surgeons.
      Extending the indication of robotics to low-incidence pathologies can take
      advantage of the opportunity to 'see the procedure' using available information
      technology, e.g. YoutubeTM that presents as an unexpectedly useful tool.
      OBJECTIVE: * To evaluate the outcome, feasibility and reproducibility of a robot
      assisted (RA) approach for simple prostatectomy (SP) in cases of high-volume
      symptomatic benign prostatic hyperplasia (HVS-BPH). PATIENTS AND METHODS: * In
      all, 35 consecutive patients underwent RASP for HVS-BPH using a previously
      described technique. * The mean prostate volume on preoperative transrectal
      ultrasonography was 106.6 mL. * All but two patients (with bladder calculi) had
      an adenoma volume of >65 mL and 27 (77.1%) >80 mL. Nine patients (25.7%) had an
      indwelling catheter. * The mean International Prostate Symptom Score (IPSS) was
      28. RESULTS: * The median operative duration was 180 min and the mean hospital
      stay was 3.17 days. * The mean catheter duration was 7.4 days and discontinuous
      or continuous catheter irrigation was required in two and seven patients,
      respectively (25.1%). * In all, 10 patients (28.6%) had practically no blood
      loss. No patients had a transfusion. * The mean postoperative peak urinary flow
      was 18.9 mL/s (P < 0.001), while the mean IPSS was 7 (P < 0.001). * For costs,
      while superficially RASP appeared more expensive than open SP (OSP), when
      considering the higher costs of hospitalisation for OSP, RASP was cheaper. Also,
      bipolar-TURP costs in patients with large-volume prostates had rather similar
      costs to RASP. CONCLUSIONS: * RASP is a feasible and reproducible procedure with
      outcome advantages when compared with the open or with other minimally invasive
      techniques (laser or laparoscopy). As a result, a RA approach is worth
      considering in cases of high-volume prostate adenomas. * Extending the indication
      of the RA approach, to the SP, requires firstly that the surgeon be proficient in
      RA surgery and secondly that as the incidence rate of HVS-BPH is low, the surgeon
      has had the opportunity to 'see the procedure'.

PMID- 22607243
TI  - Young and unlicensed: risky driving before entering the licensing system.
AB  - OBJECTIVE: On-road driving before gaining a valid license (prelicense driving)
      represents a risk for all road users. Prelicense driving among young people who
      obtained a provisional license within an enhanced graduated driver licensing
      program in Queensland, Australia, was investigated. METHODS: Recently licensed
      drivers (n = 1032) aged 17 to 19 years (M = 17.54) completed a survey exploring
      their driving experiences while on their learner's license. Six months later, 355
      of these drivers completed the same survey exploring their experiences on their
      provisional (intermediate) license. RESULTS: Twelve percent of participants
      reported prelicense driving. Prelicense drivers reported significantly more risky
      driving as learners and provisional drivers. CONCLUSIONS: Prelicense drivers not
      only place themselves and other road users at risk at the time but also continue
      to do so through their subsequent risky driving. Prelicense driving should be
      discouraged, and parents should be encouraged to monitor car use and the driving
      behavior of their children.

PMID- 22607244
TI  - Development and validation of a crash culpability scoring tool.
AB  - OBJECTIVE: Several traffic safety research techniques require researchers to
      separate crash-involved drivers into culpable and nonculpable. Nonculpable
      drivers are assumed to be randomly involved in crashes by external factors and to
      approximate a noncollision control population. If this is true, factors that
      increase crash risk should be found more often in culpable than in nonculpable
      drivers. Though a culpability scoring tool has been developed for research
      purposes, that tool does not adequately address winter driving conditions
      (Robertson and Drummer 1994). Moreover, traditional culpability scoring requires
      assessors to read and score individual collision reports. The purpose of this
      study is to develop and validate an automated, rule-based Canadian culpability
      scoring tool that is capable of rapidly scoring police crash reports from large
      administrative datasets. METHODS: We used an iterative approach to develop and
      validate our tool. First, the Robertson-Drummer culpability scoring tool was
      modified to include the extensive police report data collected in the British
      Columbia Traffic Accident System (TAS) and to account for winter driving
      conditions. This was done in consultation with traffic safety experts. The
      scoring tool was automated, employing a rule-based decision model that avoids
      interpretation of free-text reports. The scoring tool was applied to 73
      collisions (134 drivers). Two experts also reviewed these collisions and
      determined the culpability of each driver. Discrepant cases were discussed to
      understand why the scoring tool differed from the expert assessment and the
      scoring tool was modified accordingly. The final tool was compared with expert
      assessment on another sample of 96 crashes. The tool was also applied to a sample
      of 2086 crash-involved drivers with known blood alcohol concentrations (BACs) and
      the adjusted odds of culpability were calculated for several BAC ranges. RESULTS:
      The final scoring tool included 7 factors and had content validity for traffic
      safety experts. It had excellent agreement with expert scoring on the first set
      of collisions (kappa = 0.83, 95% confidence interval [CI]: 0.75-0.91) and on the
      second set (kappa = 0.84, 95% CI: 0.77-0.92). When applied to crash-involved
      drivers with known BAC levels, the scoring tool exhibited predictive validity:
      the odds of culpability increased with higher BACs, consistent with the known
      dose effect of BAC on crash risk. CONCLUSIONS: We have developed an automated
      culpability scoring tool contextualized to Canadian driving conditions. This tool
      will allow road safety researchers to assess collision responsibility in large
      administrative data sets derived from police reports.

PMID- 22607245
TI  - Traffic accidents on expressways: new threat to China.
AB  - OBJECTIVE: As China is building one of the largest expressway systems in the
      world, expressway safety problems have become serious concerns to China. This
      article analyzed the trends in expressway accidents in China from 1995 to 2010
      and examined the characteristics of these accidents. METHODS: Expressway accident
      data were obtained from the Annual Report for Road Traffic Accidents published by
      the Ministry of Public Security of China. Expressway mileage data were obtained
      from the National Statistics Yearbook published by the National Bureau of
      Statistics of China. Descriptive statistical analyses were conducted based on
      these data. RESULTS: Expressway deaths increased by 10.2-fold from 616 persons in
      1995 to 6300 persons in 2010, and the average annual increase was 17.9 percent
      over the past 15 years, and the overall other road traffic deaths was -0.33
      percent. China's expressway mileage accounted for only 1.85 percent of highway
      mileage driven in 2010, but expressway deaths made up 13.54 percent of highway
      traffic deaths. The average annual accident lethality rate [accident
      deaths/(accident deaths + accident injuries)] for China's expressways was 27.76
      percent during the period 1995 to 2010, which was 1.33 times higher than the
      accident lethality rate of highway traffic accidents. CONCLUSIONS: China's
      government should pay attention to expressway construction and safety
      interventions during the rapid development period of expressways. Related causes,
      such as geographic patterns, speeding, weather conditions, and traffic flow
      composition, need to be studied in the near future. An effective and scientific
      expressway safety management services system, composed of a speed monitoring
      system, warning system, and emergency rescue system, should be established in
      developed and underdeveloped provinces in China to improve safety on expressway.

PMID- 22607246
TI  - Evaluation of the injury impairment scale, a tool to predict road crash sequelae,
      in a French cohort of road crash survivors.
AB  - OBJECTIVE: The objective of the present study was to validate sequelae prediction
      by the Maximal Injury Impairment Score (M-IIS) in comparison with the Functional
      Independence Measure (FIM) assessed at 1-year follow-up of severe road crash
      victims. METHODS: The study population came from "the Etude et Suivi d'une
      Population d'Accidentes de la Route dans le Rhone" (ESPARR; Rhone Area Road Crash
      Victim Follow-up Study) cohort: 178 victims (with Maximal Abbreviated Injury
      Scale >= 3) of road crashes in the Rhone administrative department of France,
      aged >= 16 years and with medical examination including FIM scoring 1 year
      postaccident. Two thresholds were tested for both scores. Firstly, the relation
      between FIM and M-IIS was assessed on logistic regression models adjusted on age
      and presence of complications at 1 year postaccident. The predictive capacity of
      M-IIS was expressed as its negative and positive predictive values and was
      considered good when 80 percent or better. RESULTS: Sixty-three of the 178 adult
      subjects (mean age = 37.7 years; range = 16.1-82.9 years) showed postaccident
      complications. One-year sequelae prediction on M-IIS was greater in head, spine,
      and limb lesions but limited to slight impairments (M-IIS = 1). There was a
      significant correlation between FIM and M-IIS, although age and medical
      complications were confounding factors on certain multivariate models. The
      predictive capacity of M-IIS was low for all types of sequelae. CONCLUSIONS: M
      IIS, in this severely injured population, failed to predict sequelae at 1 year as
      measured by the FIM, despite a good correlation between the two. Complications
      are to be taken into account in assessing the M-IIS's capacity to predict
      sequelae. Further evaluation will be needed on larger series or assessment of
      other indicators and measures of sequelae at 1 year to obtain a robust tool to
      predict road crash sequelae.

PMID- 22607247
TI  - Risk factors for child and adolescent occupants, bicyclists, and pedestrians in
      motorized vehicle collisions.
AB  - OBJECTIVE: The aim was to use similar population data to examine the relative
      risk of collision injury among children of different ages and adolescents
      involved in various collision types and to elucidate the possible risk factors
      related to road collisions involving children and adolescents in a large, 2
      wheeled vehicle environment. METHODS: We used data from a society with a large
      population of motorcyclists to examine the relative risk of injury among children
      and adolescents aged 0 to 6, 7 to 9, 10 to 12, 13 to 15, and 16 to 17 years old
      who were involved in single motorized vehicle, multiple motorized vehicle,
      bicycle-to-vehicle, and pedestrian-to-vehicle collisions. Police reports for
      73,232 collision injuries between the years 2003 and 2009 were analyzed using
      multicategory logit models of the 4 collision types. RESULTS: Young (particularly
      0- to 6-year-old) child bicyclists and pedestrians were the most sensitive to
      several factors. In collisions, young child bicyclists making U-turns or being
      struck by forward-moving or right-turning motorized vehicles, on local roads,
      during the daytime, or at locations without traffic signals had the greatest risk
      of injury. Similarly, young child pedestrians running, during the daytime, or at
      locations without traffic signals had a significant risk of injury. After
      controlling for other factors, we found that 4-wheeled motorized vehicles, not
      motorcycles, presented a higher risk for injury to child passengers, bicyclists,
      and pedestrians. CONCLUSIONS: The risk of collision injury varied for the
      different groups of children in the 4 collision types. To reduce the risk of
      injury for young children, we recommend the development of road-crossing training
      tools for parents. In addition, the behaviors of children should be taken into
      consideration when developing in-vehicle assistance systems.

PMID- 22607248
TI  - Determining subgroups of teens for targeted driving injury prevention strategies:
      a latent class analysis approach.
AB  - OBJECTIVE: To utilize teen traffic safety belief profiles to improve targeting of
      resources and messages to young novice drivers. METHODS: The National Young
      Driver Survey is a nationally representative sample 5665 of 9th to 11th graders
      in the United States. Using latent class analysis, we grouped beliefs about 25
      safety-relevant behaviors into a summary set of belief profiles and related these
      profiles to demographics and driver/passenger experience. RESULTS: We determined
      5 safety belief profiles of teens: "everything" (rated most of the 25 behaviors
      as important to safety); "drivers/personal responsibility" (rated driver-related
      behaviors but few others as important); "driver drinking" (rated only driver
      alcohol use as always important); "distractions/external forces" (rated
      predominantly passenger rather than driver issues as important); and "nothing"
      (rated no issues as important). Three key groups emerged who were more likely
      than their counterparts to belong to the distractions/external forces than the
      everything class and for whom targeted messaging might be effective: males, non
      white adolescents, and teens who had experienced an injury crash as a driver.
      CONCLUSIONS: The classes appear to organize around the locus of control (LOC)
      social learning framework, with some teens perceiving crashes resulting primarily
      from their own behavior and others believing that forces in their environment
      determine the events that result in a crash. Designing interventions that help
      young drivers understand their role in crashes may help improve the safety
      behavior of young drivers. In particular, for those involved in crashes,
      interventions designed to help them understand that the crash was a result of
      their actions, rather than a random or externally driven event, may influence
      them to take control with safety-oriented behaviors.

PMID- 22607249
TI  - The occupant response to autonomous braking: a modeling approach that accounts
      for active musculature.
AB  - OBJECTIVE: The aim of this study is to model occupant kinematics in an autonomous
      braking event by using a finite element (FE) human body model (HBM) with active
      muscles as a step toward HBMs that can be used for injury prediction in
      integrated precrash and crash simulations. METHODS: Trunk and neck musculature
      was added to an existing FE HBM. Active muscle responses were achieved using a
      simplified implementation of 3 feedback controllers for head angle, neck angle,
      and angle of the lumbar spine. The HBM was compared with volunteer responses in
      sled tests with 10 ms(-2) deceleration over 0.2 s and in 1.4-s autonomous braking
      interventions with a peak deceleration of 6.7 ms(-2). RESULTS: The HBM captures
      the characteristics of the kinematics of volunteers in sled tests. Peak forward
      displacements have the same timing as for the volunteers, and lumbar muscle
      activation timing matches data from one of the volunteers. The responses of
      volunteers in autonomous braking interventions are mainly small head rotations
      and translational motions. This is captured by the HBM controller objective,
      which is to maintain the initial angular positions. The HBM response with active
      muscles is within +/-1 standard deviation of the average volunteer response with
      respect to head displacements and angular rotation. CONCLUSIONS: With the
      implementation of feedback control of active musculature in an FE HBM it is
      possible to model the occupant response to autonomous braking interventions. The
      lumbar controller is important for the simulations of lap belt-restrained
      occupants; it is less important for the kinematics of occupants with a modern 3
      point seat belt. Increasing head and neck controller gains provides a better
      correlation for head rotation, whereas it reduces the vertical head displacement
      and introduces oscillations.

PMID- 22607250
TI  - Minimization of analytical injury metrics for head impact injuries.
AB  - OBJECTIVE: To compare the predictions of the head injury criterion (HIC),
      currently used to predict the risk of traumatic brain injury in frontal vehicle
      impact and pedestrian impact tests, with the predictions of other empirical and
      analytical injury metrics. METHODS: The appropriateness of different criteria
      relative to injury metrics derived from a head finite element (FE) model is
      investigated for different deceleration pulses in this research. Empirical injury
      metrics are computed by direct calculation for different analyzed pulses. In
      addition, for each pulse full FE model simulations of a complete human head were
      performed by means of the SIMon model. The computations are used to calculate the
      analytical injury metrics. RESULTS: This article shows that an optimal head
      deceleration curve based on HIC does not minimize other analytical injury
      metrics. The results obtained in this study suggest that the HIC criterion does
      not necessarily provide the same severity ranking for different external loadings
      to the head as the injury metrics derived from the FE models. CONCLUSION:
      Countermeasures designed based only on HIC could differ significantly from those
      based on analytical injury measures computed by FE models. The use of multiple
      injury metrics is recommended given that no scalar measure seems to be positively
      and strongly correlated with relevant injury metrics.

PMID- 22607251
TI  - Gender differences in highway driving performance after administration of sleep
      medication: a review of the literature.
AB  - OBJECTIVES: It is generally assumed that there are minimal gender differences in
      the safety and efficacy of central nervous system drugs, as is evidenced by men
      and women receiving the same drug dosage. There is, however, evidence that drugs
      may have a differential effect on performance in men and women, given reported
      differences in pharmacokinetics as well as the presence or absence and severity
      of adverse effects. It is especially important to verify whether gender
      differences in performance exist in case of activities that have potentially
      dangerous outcomes such as driving a car. This review summarizes the current
      scientific evidence on gender differences in driving performance after treatment
      with hypnotic drugs. METHODS: A literature search was conducted to obtain all
      studies that conducted on-road driving tests to examine the effects hypnotic
      drugs on driving. Cross-references were checked and technical reports and raw
      data were obtained, if possible. RESULTS: Fourteen studies were evaluated. Many
      studies did not allow analyses of gender effects because only women were
      included. Others did not report data on gender analyses. Technical reports and
      additional data analyses revealed significant gender differences in driving
      performance the morning following bedtime administration of flurazepam (30 mg)
      and after middle-of-the-night administration of zolpidem (10 mg). No significant
      gender differences were found for ramelteon (8 mg), lormetazepam (1 and 2 mg),
      zaleplon (10 and 20 mg), and zopiclone (7.5 mg). CONCLUSIONS: Although the
      available data are limited, the results show that significant gender differences
      have been found for some drugs but not others. Therefore, in the future more
      research is needed to reveal potential gender differences and to determine what
      mediates them.

PMID- 22607252
TI  - Transportation behaviors in Shiraz, Iran.
AB  - OBJECTIVE: Motor vehicle accidents can occur as a result of improper driver
      behavior. There needs to be a comprehensive collection of information concerning
      driver behavior and its predisposing factors. METHODS: Study participants (500
      males and 500 females >=18 years old) living in Shiraz, Iran, were selected using
      a multistage sampling methodology. Data came from questionnaires completed using
      a face-to-face interview process. Independent variables such as age, gender,
      marital status, occupation, educational level, socioeconomic status (SES), and
      history of smoking and stress levels were compared to the dependent variables
      using a private automobile, public transportation, or motorcycle, wearing a seat
      belts, wearing safety helmets, and obeying the speed limit. Statistical
      significance was set at a P value of .05 or less. RESULTS: In general, female,
      better educated persons, and those with higher SES reported better driving
      behaviors. Better drivers also did not use tobacco or hookah. Compliance with
      driving safety factors was disappointing 49.8 percent always wore a seat belt,
      22.4 percent always wore a safety helmet (29.4% never wore a helmet), and 49.4
      percent always observed the speed limit. CONCLUSIONS: There is a need to improve
      driver safety compliance in Shiraz, Iran. One factor that can be addressed
      concerns regulation of male drivers, especially among lower SES groups.

PMID- 22607253
TI  - Analysis of risk factors affecting the severity of intersection crashes by
      logistic regression.
AB  - OBJECTIVE: The objective of this research was to study the risk factors that
      significantly influence the severity of intersection crashes for vehicle
      occupants, as well as for pedestrians and other vulnerable road users. METHODS:
      Logistic regression was applied as the method in this study to analyze a data set
      of intersection crashes involving casualties in Victoria, Australia, for the
      period January 2000 to December 2009. RESULTS: Seven risk factors obtained were
      found to be significantly associated with the severity of intersection crashes,
      including driver age and gender, speed zone, traffic control type, time of day,
      crash type, and seat belt usage. CONCLUSIONS: This study found that male drivers
      as well as older drivers (age 65 and above) had higher odds of being involved in
      fatal intersection crashes. Intersection crashes occurring between midnight and
      early morning (12:00 a.m. to 5:59 a.m.), in 100 km/h speed zones, or with no
      traffic control had a higher odds of a fatal outcome than their counterpart
      categories. Furthermore, intersection crashes involving pedestrians or a non-seat
      belt-wearing driver were more likely to lead to a fatal outcome. In general,
      identification of risk factors and the discussion of the odds ratio between
      levels on the impact of the intersection crash severity would be beneficial for
      road safety stakeholders to develop initiatives to reduce the severity of
      intersection crashes.

PMID- 22607254
TI  - Nonconformities in real-world fatal crashes--electronic stability control and
      seat belt reminders.
AB  - OBJECTIVE: Many new safety systems are entering the market. Vision Zero is a
      safety strategy aiming at the elimination of fatalities and impairing injuries by
      the use of a holistic model for safe traffic to develop a safe system. The aim of
      this article is to analyze fatalities in modern cars with respect to the Vision
      Zero model with special respect to electronic stability control (ESC) systems and
      modern seat belt reminders (SBRs). The model is used to identify and understand
      cases where cars with ESC systems lost control and where occupants were unbelted
      in a seat with seat belt reminders under normal driving conditions. METHODS: The
      model for safe traffic was used to analyze in-depth studies of fatal crashes with
      respect to seat belt use and loss of control. Vehicles from 2003 and later in
      crashes from January 2004 to mid-2010 were analyzed. The data were analyzed case
      by case. Cars that were equipped with ESC systems and lost control and occupants
      not using the seat belt in a seat with a seat belt reminder were considered as
      nonconformities. A total of 138 fatal crashes involving 152 fatally injured
      occupants were analyzed. RESULTS: Cars with ESC systems had fewer loss-of-control
      relevant cases than cars without ESC systems. Thirteen percent of the ESC
      equipped vehicles had loss-of-control-relevant crashes and 36 percent of the cars
      without ESC systems had loss-of-control-relevant crashes. The analysis indicates
      that only one car of the 9 equipped with ESC that lost control did it on a road
      surface with relevant friction when driving within the speed restriction of the
      road. In seats with seat belt reminders that are in accordance with the European
      New Car Assessment Programme's (Euro NCAP) protocol, 93 percent of the occupants
      were using a seat belt. In seats without reminders this number was 74 percent.
      CONCLUSIONS: This study shows that ESC systems result in a very significant
      reduction in fatal crashes, especially under normal driving conditions. Under
      extreme driving conditions such as speeding or extremely low friction (snow or on
      the side of the road), ESC systems can fail in keeping the car under control.
      Seat belt reminders result in higher seat belt use rates but the level of
      unbelted occupants is higher than roadside studies have indicated. The holistic
      Vision Zero approach helped in the analysis by identifying nonconformities and
      putting these into the safe systems perspective.

PMID- 22607255
TI  - Associating crash avoidance maneuvers with driver attributes and accident
      characteristics: a mixed logit model approach.
AB  - OBJECTIVE: The current study focuses on the propensity of drivers to engage in
      crash avoidance maneuvers in relation to driver attributes, critical events,
      crash characteristics, vehicles involved, road characteristics, and environmental
      conditions. The importance of avoidance maneuvers derives from the key role of
      proactive and state-aware road users within the concept of sustainable safety
      systems, as well as from the key role of effective corrective maneuvers in the
      success of automated in-vehicle warning and driver assistance systems. METHODS:
      The analysis is conducted by means of a mixed logit model that represents the
      selection among 5 emergency lateral and speed control maneuvers (i.e., "no
      avoidance maneuvers," "braking," "steering," "braking and steering," and "other
      maneuvers) while accommodating correlations across maneuvers and
      heteroscedasticity. Data for the analysis were retrieved from the General
      Estimates System (GES) crash database for the year 2009 by considering drivers
      for which crash avoidance maneuvers are known. RESULTS: The results show that (1)
      the nature of the critical event that made the crash imminent greatly influences
      the choice of crash avoidance maneuvers, (2) women and elderly have a relatively
      lower propensity to conduct crash avoidance maneuvers, (3) drowsiness and fatigue
      have a greater negative marginal effect on the tendency to engage in crash
      avoidance maneuvers than alcohol and drug consumption, (4) difficult road
      conditions increase the propensity to perform crash avoidance maneuvers, and (5)
      visual obstruction and artificial illumination decrease the probability to carry
      out crash avoidance maneuvers. CONCLUSIONS: The results emphasize the need for
      public awareness campaigns to promote safe driving style for senior drivers and
      warning about the risks of driving under fatigue and distraction being comparable
      to the risks of driving under the influence of alcohol and drugs. Moreover, the
      results suggest the need to educate drivers about hazard perception, designing a
      forgiving infrastructure within a sustainable safety systems, and rethinking in
      vehicle collision warning systems. Future research should address the
      effectiveness of crash avoidance maneuvers and joint modeling of maneuver
      selection and crash severity.

PMID- 22607256
TI  - Medical conditions, medication use, and their relationship with subsequent motor
      vehicle injuries: examination of the Canadian National Population Health Survey.
AB  - PURPOSE: To examine the effects of various medical conditions and medications on
      subsequent motor vehicle injuries (MVIs). METHOD: The National Population Health
      Survey, a large, nationally representative, longitudinal study of Canadians,
      included self-reported medical conditions of asthma, arthritis/rheumatism, back
      problems excluding arthritis, high blood pressure, migraine headaches, diabetes,
      heart disease and distress, and medication use during the past month for asthma,
      high blood pressure, diabetes, heart, codeine/pethidine (Demerol)/morphine, other
      pain relievers, antidepressants, tranquilizers, and sleeping medication. Path
      analyses were used to examine the odds of subsequent MVI for different medical
      conditions and medication use reported prior to the MVI (in the previous wave of
      the survey) while controlling for age and sex. RESULTS: Increased odds of
      subsequent MVIs were found for asthma (odds ratio [OR]: 1.864, 95% confidence
      interval [CI]: 1.281, 2.713), arthritis/rheumatism (OR: 1.659, 95% CI: 1.163,
      2.365), back problems (OR: 2.169, 95% CI: 1.624, 2.895), and migraines (OR:
      1.631, 95% CI: 1.125, 2.364) but not for high blood pressure (OR: 1.435, 95% CI:
      0.944, 2.181), diabetes (OR: 1.479, 95% CI: 0.743, 2.944), heart disease (OR:
      2.627, 95% CI: 0.941, 7.334) or distress (OR: 1.153, 95% CI: 0.840, 1.581).
      Except for migraine with codeine/pethidine/morphine, this effect persisted
      regardless of whether medication was used to treat the condition. Respondents who
      reported using certain medications, namely, codeine/pethidine/morphine (OR:
      2.215, 95% CI: 1.274, 3.850), other pain medication (OR: 1.630, 95% CI: 1.242,
      2.139), antidepressants (OR: 2.664. 95% CI: 1.602, 4.429), and sleeping
      medication (OR: 2.059, 95% CI: 1.161, 3.651), had increased odds of subsequent
      MVI, independent of related medical condition, whereas tranquillizers showed no
      increased odds of subsequent MVIs. CONCLUSIONS: This study suggests that the
      relationship between medical conditions, medications, and MVIs is complex but
      consistent with other studies.

PMID- 22607257
TI  - Driving citations and aggressive behavior.
AB  - BACKGROUND: Anger and driving have been examined in a number of studies of
      aggressive drivers and in drivers with road rage using various psychological and
      environmental study variables. However, we are not aware of any study that has
      examined the number of driving citations (an indication of problematic driving)
      and various forms of anger not related to driving. METHOD: Using a cross
      sectional approach in a consecutive sample of 331 respondents (68% female), we
      surveyed participants about the number of past driving citations, not necessarily
      convictions, and 21 aggressive behaviors using the Aggressive Behavior
      Questionnaire. RESULTS: The number of driving citations demonstrated a
      statistically significant correlation with the number of aggressive behaviors in
      the 21-item Aggressive Behavior Questionnaire. There were no differences between
      men and women. As for specific aggressive behaviors, the number of driving
      citations was statistically significantly related to punching a wall when angry,
      causing and getting into a bar fight, getting into fistfights (not in a bar),
      causing someone to have an accident, and intentionally running someone off the
      road. CONCLUSIONS: The number of driving citations, an indication of problematic
      driving, appears to be related to generally aggressive behavior. Findings
      indicate that if aggression plays a role in problematic driving, it is likely not
      limited to the road.

PMID- 22607258
TI  - Betel-quid and oral submucous fibrosis: a cross-sectional study in Hunan
      province, China.
AB  - BACKGROUND: The development of betel-quid (BQ) processing industry in Hunan has
      increased the usage of this substance and may produce significant health
      consequences. However, the update data for the prevalence of BQ chewing and its
      effect on oral submucous fibrosis (OSF) are limited. METHODS: A population-based
      survey was conducted to investigate the prevalence of BQ chewing and OSF in
      Hunan. A questionnaire interview and an oral examination were conducted. A
      multivariate logistic regression model was used to study the effect of socio
      demographic characteristics on area-specific behaviors of BQ chewing. RESULTS: A
      total of 2356 subjects participated in this survey, with a 78.5% of response
      rate. The lifetime prevalence of BQ chewing was 16.2% (2.9% for ex-chewers and
      13.3% for current-chewers). The findings from multivariate logistic regression
      model showed that a higher prevalence of this habit was among individuals who
      were males, urban residents, 15-49 years old, educated for 9-12 years, smokers,
      and drinkers. Male chewers occupied a fairly higher percentage of the combined
      use of tobacco and/or alcohol (86.1-87.5%) than the non-chewers (50.6-56.7%). The
      overall prevalence of OSF was 1.0%. Compared with the subjects without OSF (1.7
      23.2%), a significantly higher proportion of OSF patients were a current-chewer
      (62.3% in men and 100.0% in women). CONCLUSIONS: BQ chewing is a vital risk
      factor for OSF in Hunan. A high prevalence of BQ chewing found among the younger
      cohort (15-49 years old) is an urgent warning for this oral premalignant
      disorder.

PMID- 22607259
TI  - Ion channel mutations in neuronal diseases: a genetics perspective.

PMID- 22607260
TI  - Determinants of inhalant (whitener) use among street children in a South Indian
      city.
AB  - A cross-sectional study was conducted in the year 2008 among 174 children in
      observation homes in Hyderabad, India, to estimate the distribution of inhalant
      (whitener) use among this population. Data were collected using an instrument
      developed for this purpose. About 61% of the children were boys and their mean
      age was 12.2 years (range 5-18 years). Whitener use was found in 35% of the
      children along with concurrent use of other substances. Peer pressure was the
      commonest cause reported for initiating substance use. The high prevalence is an
      important concern for the Indian policymakers given the large number of street
      children in Indian cities.

PMID- 22607261
TI  - A precursor to greater European integration of social and health policies?

PMID- 22607262
TI  - Trees and/or networks to display intraspecific DNA sequence variation?
AB  - Phylogenetic trees and networks are both used in the scientific literature to
      display DNA sequence variation at the intraspecific level. Should we rather use
      trees or networks? I argue that the process of inferring the most parsimonious
      genealogical relationships among a set of DNA sequences should be dissociated
      from the problem of displaying this information in a graph. A network graph is
      probably more appropriate than a strict consensus tree if many alternative,
      equally most parsimonious, genealogies are to be included. Within the maximum
      parsimony framework, current phylogenetic inference and network-building
      algorithms are both unable to guarantee the finding of all most parsimonious (MP)
      connections. In fact, each approach can find MP connections that the other does
      not. Although it should be possible to improve at least the maximum parsimony
      approach, current implementations of these algorithms are such that it is
      advisable to use both approaches to increase the probability of finding all
      possible MP connections among a set of DNA sequences.

PMID- 22607263
TI  - Treatment of one case of cerebral palsy combined with posterior visual pathway
      injury using autologous bone marrow mesenchymal stem cells.
AB  - BACKGROUND: Cerebral palsy is currently one of the major diseases that cause
      severe paralysis of the nervous system in children; approximately 9-30% of
      cerebral palsy patients are also visually impaired, for which no effective
      treatment is available. Bone marrow mesenchymal stem cells (BMSCs) have very
      strong self-renewal, proliferation, and pluripotent differentiation potentials.
      Therefore, autologous BMSC transplantation has become a novel method for treating
      cerebral palsy. METHODS: An 11-year-old boy had a clear history of dystocia and
      asphyxia after birth; at the age of 6 months, the family members observed that
      his gaze roamed and noted that he displayed a lack of attention. A brain MRI
      examination at the age of 7 years showed that the child had cerebral palsy with
      visual impairment (i.e., posterior visual pathway injury). The patient was
      hospitalized for 20 days and was given four infusions of intravenous autologous
      BMSCs. Before transplantation and 1, 6, and 12 months after transplantation, a
      visual evoked potential test, an electrocardiogram, routine blood tests, and
      liver and kidney function tests were performed. RESULTS: The patient did not have
      any adverse reactions during hospitalization or postoperative follow-up. After
      discharge, the patient could walk more smoothly than he could before
      transplantation; furthermore, his vision significantly improved 6 months after
      transplantation, which was also supported by the electrophysiological
      examinations. CONCLUSIONS: The clinical application of BMSCs is effective for
      improving vision in a patient with cerebral palsy combined with visual
      impairment.

PMID- 22607264
TI  - Optical imaging using endogenous contrast to assess metabolic state.
AB  - Optical microscopic imaging offers opportunities to perform noninvasive
      assessments of numerous parameters associated with the biochemistry, morphology,
      and functional state of biological samples. For example, it is possible to detect
      the endogenous fluorescence from a small number of important biomolecules,
      including NADH and FAD, which are two coenzymes involved in key metabolic
      pathways such as glycolysis, the Krebs cycle, and oxidative phosphorylation.
      Here, we review different imaging approaches to isolate the fluorescence from
      these chromophores in two- and three-dimensional samples and discuss the origins
      and potential interpretation of the observed signals in terms of cell metabolic
      status. Finally, we discuss the challenges and limitations of these approaches,
      as well as important research directions that we expect will evolve in the near
      future.

PMID- 22607265
TI  - Formation of Se (0) nanoparticles by Duganella sp. and Agrobacterium sp. isolated
      from Se-laden soil of North-East Punjab, India.
AB  - BACKGROUND: Selenium (Se) is an essential trace element, but is toxic at high
      concentrations. Depending upon the geological background, the land use or on
      anthropogenic pollution, different amounts of Se may be present in soil. Its
      toxicity is related to the oxyanions selenate and selenite as they are water
      soluble and bioavailable. Microorganisms play an important role in Se
      transformations in soil and its cycling in the environment by transforming water
      soluble oxyanions into water insoluble, non-toxic elemental Se (0). For this
      study, soil samples were collected from selenium-contaminated agricultural soils
      of Punjab/India to enrich and isolate microbes that interacted with the Se cycle.
      RESULTS: A mixed microbial culture enriched from the arable soil of Punjab could
      reduce 230 mg/l of water soluble selenite to spherical Se (0) nanoparticles
      during aerobic growth as confirmed by SEM-EDX. Four pure cultures (C 1, C 4, C 6,
      C 7) of Gram negative, oxidase and catalase positive, aerobic bacteria were
      isolated from this mixed microbial consortium and identified by 16 S rDNA gene
      sequence alignment as two strains of Duganella sp. (C 1, C 4) and two strains of
      Agrobacterium sp.(C 6, C 7). SEM/TEM-EDX analyses of the culture broth of the
      four strains revealed excretion of uniformly round sharply contoured Se (0)
      nanoparticles by all cultures. Their size ranged from 140-200 nm in cultures of
      strains C 1 and C 4, and from 185-190 nm in cultures of strains C 6 and C 7. Both
      Duganella sp. revealed better selenite reduction efficiencies than the two
      Agrobacterium sp. CONCLUSIONS: This is the first study reporting the capability
      of newly isolated, aerobically growing Duganella sp. and Agrobacterium sp. from
      soils of Punjab/India to form spherical, regularly formed Se (0) nanoparticles
      from water soluble selenite. Among others, the four strains may significantly
      contribute to the biogeochemical cycling of Se in soil. Bioconversion of toxic
      selenite to non-toxic Se (0) nanoparticles under aerobic conditions in general
      may be useful for detoxification of agricultural soil, since elemental Se may not
      be taken up by the roots of plants and thus allow non-dangerous fodder and food
      production on Se-containing soil.

PMID- 22607266
TI  - Sub-optimal breastfeeding of infants during the first six months and associated
      factors in rural communities of Jimma Arjo Woreda, Southwest Ethiopia.
AB  - BACKGROUND: Studies have shown that sub-optimal breastfeeding is major
      contributor to infant and young child mortality in Ethiopia. To address this
      problem, infant and young child feeding guideline was developed in 2004 and
      interventions have been going on based on the guidelines. There is no study that
      assessed whether the infant and child feeding practices are according the
      guideline or not. This study was carried out to assess sub-optimal breastfeeding
      practices and associated factors among infants from birth to six months in rural
      communities of Jimma Arjo Woreda in the Southwest Ethiopia. METHODS: A cross
      sectional study was carried out from December to January 2009. Quantitative data
      were collected from a sample of 382 respondents supplemented by qualitative data
      generated using in-depth interviews of 15 index mothers. Multivariable logistic
      regression model was used to identify predictors of timely initiation of breast
      feeding and non-exclusive breast feeding among mother-infant pairs. RESULTS: More
      than three fourth of mothers breastfeed their infants sub-optimally. Thirty-seven
      percent of mothers initiated breastfeeding later than one hour after delivery,
      which was significantly associated with not attending formal education (AOR =
      1.05[95%CI: 1.03, 1.94]) and painful breastfeeding experiences (AOR = 5.02[95%CI:
      1.01, 10.08]). The majority (67.02%) of mothers had no knowledge about exclusive
      breastfeeding. Non-exclusive breastfeeding was negatively associated with child's
      age of 0-2 months (AOR: 0.27[95%CI: 0.16, 0.47) and 3-4 months (AOR = 0.43
      [95%CI: 0.25, 0.73) and ownership of radio (AOR = 0.56[95%CI: 0.37, 0.88]), but
      positively associated with the practice of discarding colostrums (AOR =
      1.78[95%CI: 1.09, 4.94]). CONCLUSION: The findings showed that the majority of
      mothers sub-optimally breastfeed their children in the study area. As most of the
      mothers do not have knowledge on the exclusive breast feeding. Enhancing
      community based behavior change communications using multiple channels including
      radio and folk media is recommended to reduce sub-optimal breast feeding
      practices and associated consequences among children in the study area.

PMID- 22607268
TI  - Repression of transcription of presenilin-1 inhibits gamma-secretase independent
      ER Ca2+ leak that is impaired by FAD mutations.
AB  - Genetic deletion or mutations of presenilin genes (PS1/PS2) cause familial
      Alzheimer's disease and calcium (Ca2+) signaling abnormalities. PS1/PS2 act as
      endoplasmic reticulum (ER) Ca2+ leak channels that facilitate passive Ca2+ leak
      across ER membrane. Studies with PS1/PS2 double knockout (PS1/PS2-DKO) mouse
      embryonic fibroblasts showed that PS1/PS2 were responsible for 80% of passive
      Ca2+ leak from the lumen of endoplasmic reticulum to cytosol. Transient
      transfection of the wild type PS1 expression construct increased cytoplasmic Ca2+
      as a result of Ca2+ leak across ER membrane whereas the FADPS1 (PS1-M146V)
      mutation construct alone or in combination with the wild type PS1 expression
      construct abrogated Ca2+ leak in SK-N-SH cells. Inhibition of basal c-jun-NH2
      terminal kinase (JNK) activity by JNK inhibitor SP600125 repressed PS1
      transcription and PS1 protein expression by augmenting p53 protein level in SK-N
      SH cells (Lee and Das 2008). In this report we also showed that repression of PS1
      transcription by JNK inhibitor SP600125 inhibited passive Ca2+ leak across ER
      membrane which could be rescued by expressing PS1 wild type and not by expressing
      FADPS1 (PS1-M146V) under a SP600125 non-responsive promoter. Treatment of SK-N-SH
      cells with SP600125 also triggered InsP3R-mediated Ca2+ release from the ER by
      addition of 500 nM bradykinin, an agonist of InsP3 receptor (InsP3R1) without
      changing the expression of InsP3R1. This data confirms that SP600125 increases
      the Ca2+ store in the ER by inhibiting PS1-mediated Ca2+ leak across ER membrane.
      p53, ZNF237 and Chromodomain helicase DNA-binding protein 3 which are repressors
      of PS1 transcription, also reduced Ca2+ leak across ER membrane in SK-N-SH cells
      but gamma-secretase inhibitor or dominant negative gamma-secretase-specific PS1
      mutant (PS1-D257A) had no significant effect. Therefore, p53, ZNF237, and
      Chromodomain helicase DNA-binding protein 3 inhibit the function ER Ca2+ leak
      channels to regulate both ER and cytoplasmic Ca2+ levels and may potentially
      control Ca2+-signaling function of PS1.

PMID- 22607269
TI  - Safety, tolerability and pharmacokinetics of single and multiple doses of a novel
      sigma-1 receptor antagonist in three randomized phase I studies.
AB  - AIM: To assess the safety, tolerability, pharmacodynamics and pharmacokinetics in
      healthy subjects of a novel, highly selective, sigma-1 receptor antagonist
      (S1RA). METHODS: Three randomized, double-blind, placebo-controlled trials
      evaluated single oral doses (5-500 mg, study 101; 500-800 mg, study 106) and
      multiple doses (50-400 mg once daily for 8 days, study 102) of S1RA. Safety and
      tolerability were assessed by adverse event reporting, clinical laboratory,
      physical examinations, vital signs and electrocardiography, including Holter
      monitoring. Pharmacodynamic assessments included computerized cognitive testing.
      Plasma samples were analyzed using validated HPLC-MS/MS methods. RESULTS: One
      hundred and seventy-five subjects were enrolled. Single and multiple doses were
      safe and well tolerated, with no serious adverse events. The most common side
      effects were headache and dizziness. The highest single doses were associated
      with some mild to moderate transient CNS effects. The maximum tolerated dose was
      not reached. There were no clinically significant changes in the
      electrocardiogram (ECG), 24 h Holter monitoring, or in vital signs and laboratory
      assessments. Subjective CNS pharmacodynamics evaluations showed no relevant
      differences vs. placebo. Cognitive testing showed no effects on visual memory,
      executive function, attention or somnolence, while revealing some transient
      slowing of response for simple reaction time and choice reaction time at 2 h
      following the administration of higher doses. A fast absorption, rapid
      distribution and slow elimination were observed (t(max) 0.75-2.0 h, t(1/2)
      compatible with once a day administration) and steady-state was reached. No
      gender differences were observed. CONCLUSIONS: S1RA exhibited an acceptable
      safety, tolerability, pharmacodynamic and pharmacokinetic profile in healthy
      subjects over the dose range studied.

PMID- 22607271
TI  - Natural product-likeness score revisited: an open-source, open-data
      implementation.
AB  - BACKGROUND: Natural product-likeness of a molecule, i.e. similarity of this
      molecule to the structure space covered by natural products, is a useful
      criterion in screening compound libraries and in designing new lead compounds. A
      closed source implementation of a natural product-likeness score, that finds its
      application in virtual screening, library design and compound selection, has been
      previously reported by one of us. In this note, we report an open-source and open
      data re-implementation of this scoring system, illustrate its efficiency in
      ranking small molecules for natural product likeness and discuss its potential
      applications. RESULTS: The Natural-Product-Likeness scoring system is implemented
      as Taverna 2.2 workflows, and is available under Creative Commons Attribution
      Share Alike 3.0 Unported License at http://www.myexperiment.org/packs/183.html.
      It is also available for download as executable standalone java package from
      http://sourceforge.net/projects/np-likeness/under Academic Free License.
      CONCLUSIONS: Our open-source, open-data Natural-Product-Likeness scoring system
      can be used as a filter for metabolites in Computer Assisted Structure
      Elucidation or to select natural-product-like molecules from molecular libraries
      for the use as leads in drug discovery.

PMID- 22607270
TI  - Measuring quality of life impairment in skeletal muscle channelopathies.
AB  - BACKGROUND AND PURPOSE: Fatigue and pain have been previously shown to be
      important determinants for decreasing quality of life (QoL) in one report in
      patients with non-dystrophic myotonia. The aims of our study were to assess QoL
      in skeletal muscle channelopathies (SMC) using INQoL (individualized QoL) and SF
      36 questionnaires. METHODS: We administered INQoL and SF-36 to 66 Italian
      patients with SMC (26: periodic paralysis, 36: myotonia congenita and 4: Andersen
      Tawil) and compared the results in 422 patients with myotonic dystrophies (DM1:
      382; and DM2: 40). RESULTS: (i) INQoL index in SMC is similar to that in DMs (P =
      0.79). (ii) Patients with myotonia congenita have the worst perception of QoL.
      (iii) Myotonia has the most detrimental effect on patients with myotonia
      congenita, followed by patients with DM2 and then by patients with DM1 and
      hyperkalemic periodic paralysis. (iv) Pain is a significant complaint in patients
      with myotonia congenita, hypokalemic periodic paralysis and DM2 but not in DM1.
      (v) Fatigue has a similar detrimental effect on all patient groups except for
      patients with hyperkalemic periodic paralysis in whom muscle weakness and
      myotonia more than fatigue affect QoL perception. (vi) Muscle symptoms considered
      in INQoL correlate with physical symptoms assessed by SF-36 (R from -0.34 to 
      0.76). CONCLUSIONS: QoL perception in patients with SMC is similar to that of
      patients with DMs, chronic multisystem disabling conditions. Our results provide
      information to target treatment and health care of these patients. The
      sensitivity of INQoL to changes in QoL in the SMC needs to be further explored in
      longitudinal studies.

PMID- 22607272
TI  - Caries experience in the permanent dentition among first- and second-grade
      schoolchildren in southeastern Estonia.
AB  - OBJECTIVE: This study aims to assess the caries experience among first- and
      second-grade children in the elementary schools of southeastern Estonia.
      MATERIALS AND METHODS: A representative sample of 485 children was studied. The
      mean age of children in the first grade was 7.8 years (SD = 0.35) and in the
      second grade 8.8 years (0.38). The clinical examinations using ICDAS criteria
      were completed by four calibrated examiners. The inter- and intra-examiner
      consistency of the examiners was high (surface and tooth-based kappa >0.9).
      RESULTS: The mean caries experience of dentinal caries lesions was 0.8 (D 4-6
      MFT) and 1.6 (D 4-6 MFS) among the first graders and 1.1 (D 4-6 MFT) and 1.6 (D 4
      6 MFS) among the second graders. The mean caries enamel lesions among the first
      graders was 1.6 (D1-3T) and 2.2 (D1-3S) and among the second graders 2.1 and 3.0,
      respectively. The most affected surfaces were the occlusal surfaces of the lower
      first molars. The prevalence of sealants was very low-only 2.4% of the first
      molars were sealed among the first graders and 3.9% among the second graders.
      There were no statistically significant differences in caries experience or in
      the provision of restorative treatment between the schools. CONCLUSIONS: Caries
      experience is high in southeastern Estonia. Preventive programs are urgently
      needed.

PMID- 22607273
TI  - Genetic discrimination: international perspectives.
AB  - Genetic discrimination (GD) is a complex, multifaceted ethical, psychosocial, and
      legal phenomenon. It is defined as the differential treatment of asymptomatic
      individuals or their relatives on the basis of their real or assumed genetic
      characteristics. This article presents an overview of GD within the contemporary
      international context. It describes the concept of GD and its contextual
      features, reviews research evidence regarding people's experiences of GD and the
      impact of GD within a range of domains, and provides an overview of legal and
      policy responses to GD that have emerged globally. We argue that GD is a
      significant and internationally established phenomenon that requires multilevel
      responses to ensure social justice and equitable outcomes for all citizens.
      Future research should monitor GD and its impacts within the community as well as
      institutions and should evaluate the effectiveness of legislative, policy,
      community education, and systemic responses.

PMID- 22607275
TI  - Prevalence of sexual activity and associated factors in hypertensive males and
      females in China: a cross-sectional study.
AB  - BACKGROUND: Hypertension is an important factor contributing to sexual
      dysfunction. The number of people with hypertension is increasing in China, but
      research into sexual life, which has implications for quality of life, is
      limited. We aimed to compare sexual activity and the influence of daily behaviors
      and sexual domain of hypertensive males and females in south China. METHODS: A
      cross-sectional study was conducted at the health care center of a university
      affiliated hospital from 2007 to 2008. We enrolled 502 subjects with hypertension
      (225 males, 48.79 +/- 7.39 years old; 277 females, 48.26 +/- 6.93 years old) and
      173 with normotension (82 males, 45.69 +/- 6.58 years old; 91 females, 46.14 +/-
      7.03 years old), all sexually active. All subjects completed a self-administered
      questionnaire on sexual activity before a routine physical check-up. Data were
      collected on sociodemographic and clinical characteristics, use of cigarettes and
      intake of beverages (including alcohol). RESULTS: Hypertensive and normotensive
      subjects differed in frequency of orgasms and of sexual satisfaction, as well as
      duration of sexual activity. For hypertensive men, low frequency of sexual
      activity, orgasms and satisfaction were associated with unemployed or retired
      status than physical labor work (odds ratio [OR] 0.28 [95% confidence interval
      (95% CI) 0.12-0.69], 0.32 [0.12-0.86], 0.33 [0.19-0.88], respectively; p < 0.05),
      and long sexual duration was associated with never drinking alcohol than heavy
      drinking (OR 4.49 [1.28-6.41]). For hypertensive women, low frequency and
      duration of sexual activity and low satisfaction were associated with never
      drinking tea than heavy tea drinking (OR 0.42 [0.18-0.96], 0.49 [0.24-0.98], 0.29
      [0.14-0.64], respectively; p < 0.05). Medication use and electrocardiography
      results were not associated with sexual activity for hypertensive patients.
      CONCLUSIONS: For hypertensive people in China, lifestyle factors are associated
      with sexual dysfunction, which differs by the sex of the person. Further research
      needs to examine serum hormone levels to validate the result.

PMID- 22607277
TI  - An explant based-method for differentiating adipocytes from equine adipose
      tissue.
AB  - Culturing adipocytes enables fine control of experimental conditions and helps
      minimise animal use. This report describes an explant-based method for isolating
      stromal-vascular cells from equine adipose tissue that enables use of small
      amounts of tissue. Subcutaneous and mesenteric adipose tissues were harvested
      post mortem and stromal-vascular cells grown from explants, prior to testing the
      capacity of several differentiation media to induce lipid droplet formation and
      increase transcript abundance of adipocyte markers. Inclusion of rosiglitazone at
      1 and 5 umol/l concentrations, along with other media components, induced
      differentiation of cultured equine stromal-vascular cells derived from
      subcutaneous and mesenteric adipose tissues.

PMID- 22607276
TI  - Comparative landscape genetic analyses show a Belgian motorway to be a gene flow
      barrier for red deer (Cervus elaphus), but not wild boars (Sus scrofa).
AB  - While motorways are often assumed to influence the movement behaviour of large
      mammals, there are surprisingly few studies that show an influence of these
      linear structures on the genetic make-up of wild ungulate populations. Here, we
      analyse the spatial genetic structure of red deer (Cervus elaphus) and wild boars
      (Sus scrofa) along a stretch of motorway in the Walloon part of Belgium.
      Altogether, 876 red deer were genotyped at 13 microsatellite loci, and 325 wild
      boars at 14 loci. In the case of the red deer, different genetic clustering tools
      identified two genetic subpopulations whose borders matched the motorway well.
      Conversely, no genetic structure was identified in the case of the wild boar.
      Analysis of isolation-by-distance patterns of pairs of individuals on the same
      side and on different sides of the motorway also suggested that the road was a
      barrier to red deer, but not to wild boar movement. While telemetry studies seem
      to confirm that red deer are more affected by motorways than wild boar, the red
      deer sample size was also much larger than that of the wild boars. We therefore
      repeated the analysis of genetic structure in the red deer with randomly sub
      sampled data sets of decreasing size. The power to detect the genetic structure
      using clustering methods decreased with decreasing sample size.

PMID- 22607278
TI  - Five days of no anticoagulation or antiplatelet therapy and NovoSeven
      administration in a HeartWare HVAD patient.
AB  - Postoperative bleeding is the most common complication following the implantation
      of ventricular assist devices. This is a case report of a HeartWare HVAD patient
      with intractable bleeding following chest tube insertion necessitating massive
      blood transfusion and multiple thoracotomies. Anticoagulation and antiplatelet
      therapy were discontinued and intravenous NovoSeven was administered as last
      resort. Bleeding ceased immediately and no pump-related issues were observed.
      However, thrombus formation in the right atrium and superior vena cava was
      detected.

PMID- 22607279
TI  - Eyelash trichomegaly: review of congenital, acquired, and drug-associated
      etiologies for elongation of the eyelashes.
AB  - Eyelash trichomegaly is defined as eyelashes which are found to be of increased
      length, thickness, and pigmentation. This unique finding can be present at birth
      as part of a variety of congenital syndromes or as a benign familial trait. There
      are also acquired conditions and drugs that are known to cause these changes.
      Case reports and clinical studies in the medical literature concerning eyelash
      trichomegaly were investigated and summarized to compile a comprehensive review
      of the etiology of eyelash trichomegaly. Previously published reviews and studies
      that report on the finding of increased generalized hair growth and which do not
      specifically mention eyelashes were not included. Trichomegaly of the eyelashes
      may occur as a key feature among rare congenital syndromes, develop in
      association with certain acquired diseases, or present as an intended or
      treatment-related adverse drug effect. Eyelash trichomegaly may be present from
      birth or manifest later in life in association with acquired diseases or drug
      therapy. The relevance of this finding may be benign, however eyelash
      trichomegaly in some individuals can be a symptom for immune dysfunction or a
      clinical measure of response to drug therapy.

PMID- 22607280
TI  - Sweaty skin, background and assessments.
AB  - Overproduction of sweat, sweaty skin, and body malodors are felt unpleasant by
      many people in diverse social groups. This review summarizes the functional
      aspects of the eccrine, apocrine, and apoeccrine sweat glands as encountered in
      health and disease. A series of measuring methods are conveniently used to
      explore any trouble in sweat production. These include the gravimetric method,
      water evaporation quantification, skin staining procedures, dye injections,
      casting replicas, average electrometric assessments, and skin capacitance mapping
      / imaging (SCM). Qualitative assessment is provided by collection of sweat and
      volatile compounds followed by chromatographic analysis. At present, SCM appears
      to be the most valuable method for assessing the number of active glands and
      their individual sweat production by the eccrine and apoeccrine glands.

PMID- 22607281
TI  - Climate change and skin disease: a review of the English-language literature.
AB  - Climate change describes variation in regional or global climates over time. The
      question of how climate change affects skin disease remains largely unanswered.
      We reviewed the English-language literature describing the influence of climate
      change on skin. Relatively few publications detail aspects of how climate change
      affects skin. Direct effects include the effects of extreme weather events, and
      indirect effects include the effects of longer-term changes in patterns of
      infections and infestations worldwide. The effect of climate change on skin is
      unclear, and more studies on this topic are needed.

PMID- 22607282
TI  - Multiple yellowish plaques in cerebriform pattern on the right elbow. Nevus
      lipomatosus cutaneous superficialis (NLCS)--classical type of Hoffmann and
      Zurhelle.

PMID- 22607283
TI  - Scientific productivity of OECD countries in dermatology journals within the last
      10-year period.
AB  - BACKGROUND:   Scientific productivity is closely related to gross income,
      population, and cultures of the countries. Every country, more or less, has a
      responsibility of contributing to science. MATERIALS AND METHODS: The
      publications, citations received, and the h-index under the category of
      "dermatology" in 43 journals between the years of 1999-2003 and 2004-2008
      according to the ISI JCR data of 2008 were examined individually for each OECD
      country. RESULTS: In the journals under the category of "dermatology" between the
      years of 1999 and 2008, there were 89,319 publications, 76,899 of which were
      published by OECD countries. USA ranks first with 27,109 publications and 196,002
      citations; Germany, Japan, England, and France are the other countries among the
      top five, respectively. Regarding the number of publications, Turkey and Korea
      are among the top 10 by surpassing many Northern European countries. With regard
      to h-index and citations, Northern European countries and Canada rank among the
      top 10, while Japan, Spain, Turkey, and Korea rank behind. The number of
      publications showed a significant correlation with the number of citations,
      population, gross domestic product, and h-index. CONCLUSIONS:   Nearly half of
      all publications were performed by the European origin OECD countries, and one
      third of all publications were performed by USA. Journals from Germany and
      France, which are published in their own language, receive fewer citations, but
      they contribute a lot to these countries with respect to the number of
      publications.

PMID- 22607284
TI  - Atopic dermatitis: correlation between non-damaged skin barrier function and
      disease activity.
AB  - BACKGROUND:   Atopic dermatitis (AD) is a chronic dermatosis, predominant in
      childhood, characterized by pruritus and eczematous-type lesions with xerosis as
      the prominent clinical sign. OBJECTIVES:   To analyze the correlation between
      biophysical measurements of skin barrier function and other assessment criteria
      of clinical severity according to Rajka and Langeland's criteria. METHODS:  
      Biophysical measurements [transepidermal water loss (TEWL) and corneometry] were
      obtained from 120 patients with the diagnosis of AD. Serum levels of IgE were
      also evaluated. RESULTS:   A significant correlation between corneometry, TEWL,
      and clinical severity of AD was found. Data showed an inverse correlation between
      corneometry, TEWL, and AD severity, and a significant difference (P < 0.001)
      between mean of corneometry and TEWL and AD severity (mild, moderate, and
      severe). As for IgE levels, corneometry had significant negative correlation, in
      contrast with TEWL, which showed a significant positive correlation (P < 0.001).
      CONCLUSION:   Biophysical measurements of skin barrier in non-lesional skin of AD
      may work as an evaluation factor for AD severity.

PMID- 22607285
TI  - Progress in epidermolysis bullosa: summary of a workshop in CILAD-2010*.
AB  - BACKGROUND:   Epidermolysis bullosa (EB), a group of blistering disorders,
      manifests with fragility of skin and mucous membranes, with considerable
      phenotypic variability. As many as 15 distinct genes have been shown to harbor
      mutations inheritable forms of EB. The types and combinations of mutations in
      these genes and their consequences at the mRNA and protein levels, when placed on
      the affected individuals' genetic background and the external trauma, explain the
      spectrum of phenotypes encountered in this disorder. METHODS:   A group of
      eminent researchers and physician-scientists convened in Cancun, Mexico, as part
      of the CILAD-2010 Meeting, to discuss the most recent progress in diagnosis and
      management of patients with EB, with emphasis on development of novel treatment
      strategies. RESULTS:   The information on specific mutations in the candidate
      genes has been helpful in establishing genotype/phenotype correlations and has
      formed the basis for prenatal testing and preimplantation of genetic diagnosis
      for EB. CONCLUSIONS:   In spite of the progress in molecular genetics of EB,
      there is no specific and effective treatment, and management of these patients
      continues to present tremendous clinical challenges. This overview summarizes the
      presentations and discussions in this international workshop.

PMID- 22607287
TI  - ADULT syndrome due to an R243W mutation in TP63.
AB  - Acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome is a rare, autosomal dominant
      form of ectodermal dysplasia due to TP63 mutations. ADULT syndrome is much less
      common than the more classical forms of TP63-associated ectodermal dysplasias,
      such as ectrodactyly-ectodermal dysplasia-cleft lip/palate (EEC) syndrome and
      ankyloblepharon-ectodermal defects-cleft lip/palate syndrome. ADULT syndrome is
      characterized by ectrodactyly, syndactyly, and excessive freckling, in addition
      to more typical ectodermal defects, including hypodontia, lacrimal duct
      anomalies, hypotrichosis, and onychodysplasia. Unlike some of the other TP63
      associated ectodermal dysplasias, ADULT syndrome lacks clefting and
      ankyloblepharon. Here, we report a three-generation family with ADULT syndrome
      due to an R243W mutation in TP63, a mutation that has previously been described
      in one patient with ADULT syndrome and eight unrelated patients with EEC
      syndrome.

PMID- 22607286
TI  - A comparative study of the impairment of quality of life in Czech children with
      atopic dermatitis of different age groups and their families.
AB  - BACKGROUND: Atopic dermatitis (AD) still remains one of the most common childhood
      inflammatory skin diseases. As a chronic disease, it can have a physical and
      psychological effect on social functioning of the affected child as well as their
      family. The objective of this study was to evaluate the quality of life of
      children with AD of different age groups and their families. METHODS: A total of
      203 children with a diagnosis of AD from newborn to 18 years of age and 202 of
      their parents took part in our study (as one parent did not return the
      questionnaire). All participants, according to their age, completed the following
      questionnaires: Infants' Dermatitis Quality of Life Index (IDQOL); Children's
      Dermatology Life Quality Index (CDLQI) - text and cartoon version; and Dermatitis
      Family Impact questionnaire (DFI). RESULTS: The mean total IDQOL score in our
      study was 8.18 (SD = 5.84, n = 120). The mean total CDLQI scores in the groups of
      children from 7 to 13 and from 14 to 18 years were 8.58 (SD = 4.98, n = 48) and
      9.89 (SD = 5.26, n = 35). There was also a proven influence of the child's AD on
      the quality of life of his parents with the mean score: 7.98 (SD = 6.41, n =
      202). CONCLUSIONS: The study demonstrated and confirmed that AD significantly
      impairs the children's quality of life in all age groups and also quality of life
      of their families. Such data give us patient-oriented information that is of
      great importance for understanding the situation of individuals with AD and its
      influence on members of their family.

PMID- 22607288
TI  - Atypical Hansen's disease presenting as florid verrucous plaques on the lower
      extremities: a case report.
AB  - BACKGROUND: Verrucous leprosy is rare, with only 18 cases reported in the
      literature. Visceral involvement is frequent but often overlooked, causing
      significant morbidity and mortality. CASE REPORT: A 45-year-old Filipino male
      with a 16-year history of hyperpigmented, hypoesthetic plaques, amputated digits,
      enlarged ulnar nerve, and cardiovascular congestion was diagnosed with Hansen's
      disease-lepromatous type. He had multiple cauliflower-like nodules and plaques
      with foul-smelling discharge on the lower extremities presenting a diagnostic
      dilemma. After an exhaustive search, the causative agent for these verrucous
      nodules was confirmed to still be Mycobacterium leprae. In addition, he had
      glomerulonephritis, hypertension, congestive heart failure, deep venous
      thrombosis, neuritis, keratitis, and glaucoma, which are all complications of
      advanced leprosy and multiple attacks of erythema nodosum leprosum reactions.
      CONCLUSION: He was treated with a multibacillary regimen of Rifampicin, Dapsone,
      Clofazimine, and systemic corticosteroids, with remarkable improvement.

PMID- 22607289
TI  - Cutaneous sporotrichosis: a six-year review of 19 cases in a tertiary referral
      center in Malaysia.
AB  - BACKGROUND: Sporotrichosis is a subcutaneous fungal infection caused by a
      thermally dimorphic aerobic fungus, Sporothrix schenckii. It results from
      traumatic inoculation or contact with animals. Most cases were reported mainly in
      the tropics and subtropics. OBJECTIVE:   The objective of our study is to assess
      the clinical characteristic of cutaneous sporotrichosis among our patients.
      METHODOLOGY: We performed a retrospective review of all cases diagnosed with
      cutaneous sporotrichosis from July 2004 to June 2010. Patients' medical records
      were retrieved and analyzed according to demography, preceding trauma, sites of
      lesions, clinical subtypes, treatment, and clinical response. RESULTS: Nineteen
      cases were diagnosed with cutaneous sporotrichosis with a male/female ratio of
      9:10. Thirteen cases (68.4%) were able to recall preceding trauma, and seven of
      them reported cat scratches or cat bites. Lymphocutaneous sporotrichosis was
      observed in 13 cases (68.4%) followed by four cases of fixed cutaneous
      sporotrichosis and two cases of disseminated sporotrichosis. Histologically, 11
      cases (57.8%) demonstrated a granulomatous reaction. Sporothrix schenckii was
      cultured in 12 cases (63.2%). Thirteen cases (68.4%) were successfully treated
      with oral itraconazole alone for a mean duration of 15.6 weeks. Two cases with
      disseminated cutaneous sporotrichosis were treated with intravenous amphotericin
      B. CONCLUSION:   Lymphocutaneous sporotrichosis was the most common subtype of
      cutaneous sporotrichosis in our series, with cat scratches or bites being the
      most common preceding trauma. Oral itraconazole was highly effective for the
      localized subtypes, whereas intravenous amphotericin B was required in
      disseminated cutaneous sporotrichosis.

PMID- 22607290
TI  - Langerhans cell histiocytosis presenting as a multi-system disorder in an infant.

PMID- 22607291
TI  - Human papillomavirus type 73 associated with multiple cutaneous squamous cell
      carcinomas in an immunosuppressed patient.

PMID- 22607292
TI  - Erythema ab igne caused by laptop computer gaming--a case report.

PMID- 22607293
TI  - Rowell's syndrome: a distinct clinical entity or a coincidence of diagnoses?

PMID- 22607294
TI  - Mohs micrographic surgery for verrucous carcinoma of the anogenital area: report
      of two cases.
AB  - BACKGROUND:   Verrucous carcinoma (VC) of the anogenital area is an uncommon
      variant of squamous cell carcinoma (SCC). Its treatment is not standardized, but
      surgical excision must be performed if possible. The traditional approach does
      not distinguish between conventional SCC and VC, despite the extremely low
      metastatic potential of VC. Accordingly, most patients reported in the literature
      have been treated with radical surgery, including regional lymphadenectomy.
      METHODS:   We report two cases in order to describe the oncologic, functional,
      and esthetic results achieved by Mohs micrographic surgery (MMS) in the treatment
      of this disease. RESULTS:   Good functional and esthetic results were achieved in
      both patients. No local or nodal relapses were detected during the respective 12-
      and 27-month follow-ups. CONCLUSIONS:   Early recognition of VC and the proper
      evaluation of deep biopsies will avoid misdiagnosis as SCC and may prevent the
      occurrence of unnecessary disfiguring interventions. The MMS technique may be
      considered as a surgical approach in genitoanal VC, although further research is
      required to confirm this.

PMID- 22607295
TI  - Natural coniferous resin salve used to treat complicated surgical wounds: pilot
      clinical trial on healing and costs.
AB  - Resin is a natural product of coniferous trees. Salves manufactured from spruce
      resin (Picea abies) have been used for centuries to treat wounds and skin
      infections. We report a pilot clinical trial designed to investigate healing
      rates, factors that contribute to delayed wound healing, cost-effectiveness, and
      incidence of allergic reactions when resin salve is used to treat complicated
      surgical wounds. The trial involved 23 patients in whom wound healing after
      surgery was delayed. These patients were assigned to resin salve treatment. The
      primary outcome measure was the number of days to complete wound healing.
      Secondary objectives included an assessment of factors contributing to delayed
      wound healing, an estimation of associated costs, and an investigation into the
      occurrence of allergic reactions related to resin salve therapy. The study
      achieved a healing rate of 100%. The mean +/- SD healing time was 43 +/- 24 days.
      The mean +/- SD wound size (length * width * depth) was (29 +/- 19) * (12 +/- 7)
      * (4 +/- 3) mm. Wound size, use of corticosteroids or other immunosuppressants,
      and immobilization were statistically significant (P < 0.05) contributors to
      delayed wound healing and impaired re-epithelialization. The total mean +/- SD
      costs of the resin salve treatment were ?45.0 +/- 26.0 per patient during the
      entire treatment period and ?1.2 +/- 0.5 per treatment day. The rate of allergic
      reactions was 0%. The results of this pilot trial indicate that complicated
      surgical wounds may be treated successfully with resin salve. The treatment
      method is clinically effective and cost-effective, and the rate of allergic
      reactions is low.

PMID- 22607296
TI  - Co-treatment with retinyl retinoate and a PPARalpha agonist reduces retinoid
      dermatitis.
AB  - BACKGROUND:   Retinoids have been used for the treatment of skin disorders such
      as acne, psoriasis, and photoaging. However, despite their beneficial effects,
      topical retinoids often cause severe local irritation called retinoid dermatitis.
      We previously developed a novel vitamin A derivative, retinyl retinoate, which
      induces less irritation and affords excellent tolerance. In this study, we
      examined whether co-treatment with topical peroxisome proliferator-activated
      receptor-alpha (PPARalpha) agonists (e.g. WY14643) reduce retinoid dermatitis in
      hairless mouse skin. METHODS:   The effect of concomitant treatment with a
      PPARalpha agonist on retinoid dermatitis in hairless mouse epidermis was
      evaluated by measuring transepidermal water loss, epidermal histology, and
      cytokine expression. RESULTS:   Retinyl retinoate induced less severe retinoid
      dermatitis than retinoic acid. Topical application of a PPARalpha agonist
      improved the stratum corneum structure and function, reduced mRNA expression of
      interleukin (IL)-1alpha, tumor necrosis factor-alpha and IL-8, and inhibited ear
      edema induced by retinoic acid or retinyl retinoate. CONCLUSIONS:   Our results
      indicate that PPARalpha agonists can potentially be used to improve retinoid
      dermatitis. We suggest that co-treatment with retinyl retinoate and a PPARalpha
      agonist may reduce or prevent detrimental alterations in retinoid-treated skin.

PMID- 22607297
TI  - Psoriasiform variant of porokeratotic eccrine ostial and dermal duct nevus.

PMID- 22607298
TI  - Pillar knocker's callosities.

PMID- 22607299
TI  - Editorial Board Meeting, International Journal of Dermatology, San Diego, March
      18, 2012: beginning the 51th year!

PMID- 22607300
TI  - American Academy of Dermatology 70th Annual Meeting, San Diego, March 16-20,
      2012.

PMID- 22607305
TI  - Upcoming New Feature in the Journal of Biomolecular Structure & Dynamics.

PMID- 22607306
TI  - Sixth Conversation in the Discipline Biomolecular Stereodynamics State University
      of New York at Albany, June 06-10, 1989.

PMID- 22607302
TI  - Behavioral activation-based guided self-help treatment administered through a
      smartphone application: study protocol for a randomized controlled trial.
AB  - BACKGROUND: The need for cost-effective interventions for people suffering from
      major depressive disorders is essential. Behavioral activation is an intervention
      that can largely benefit from the use of new mobile technologies (for example
      smartphones). Therefore, developing smartphone-based behavioral activation
      interventions might be a way to develop cost-effective treatments for people
      suffering from major depressive disorders. The aim of this study will be to test
      the effects of a smartphone-delivered behavioral activation treatment. METHODS:
      The study will be a randomized controlled trial with a sample size of 120
      participants, with 60 patients in each group. The treatment group includes an 8
      week smartphone-based behavioral activation intervention, with minimal therapist
      contact. The smartphone-based intervention consists of a web-based
      psychoeducation, and a smartphone application. There is also a back-end system
      where the therapist can see reports from the patients or activities being
      reported. In the attention control group, we will include brief online education
      and then recommend use of a smartphone application that is not directly aimed at
      depression (for example, 'Effective meditation'). The duration of the control
      condition will also be 8 weeks. For ethical reasons we will give the participants
      in the control group access to the behavioral activation treatment following the
      8-week treatment period. DISCUSSIONS: We believe that this trial has at least
      three important implications. First, we believe that smartphones can be
      integrated even further into society and therefore may serve an important role in
      health care. Second, while behavioral activation is a psychological treatment
      approach for which there is empirical support, the use of a smartphone
      application could serve as the therapist's prolonged arm into the daily life of
      the patient. Third, as we have been doing trials on guided Internet treatment for
      more than 10 years it is now time to move to the next generation of information
      technology - smartphones - which are not only relevant for Swedish conditions but
      also for developing countries in the world which are increasingly empowered by
      mobile phones with Internet connection. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01463020.

PMID- 22607308
TI  - Tropical forest carbon balance in a warmer world: a critical review spanning
      microbial- to ecosystem-scale processes.
AB  - Tropical forests play a major role in regulating global carbon (C) fluxes and
      stocks, and even small changes to C cycling in this productive biome could
      dramatically affect atmospheric carbon dioxide (CO(2) ) concentrations.
      Temperature is expected to increase over all land surfaces in the future, yet we
      have a surprisingly poor understanding of how tropical forests will respond to
      this significant climatic change. Here we present a contemporary synthesis of the
      existing data and what they suggest about how tropical forests will respond to
      increasing temperatures. Our goals were to: (i) determine whether there is enough
      evidence to support the conclusion that increased temperature will affect
      tropical forest C balance; (ii) if there is sufficient evidence, determine what
      direction this effect will take; and, (iii) establish what steps should to be
      taken to resolve the uncertainties surrounding tropical forest responses to
      increasing temperatures. We approach these questions from a mass-balance
      perspective and therefore focus primarily on the effects of temperature on inputs
      and outputs of C, spanning microbial- to ecosystem-scale responses. We found
      that, while there is the strong potential for temperature to affect processes
      related to C cycling and storage in tropical forests, a notable lack of data
      combined with the physical, biological and chemical diversity of the forests
      themselves make it difficult to resolve this issue with certainty. We suggest a
      variety of experimental approaches that could help elucidate how tropical forests
      will respond to warming, including large-scale in situ manipulation experiments,
      longer term field experiments, the incorporation of a range of scales in the
      investigation of warming effects (both spatial and temporal), as well as the
      inclusion of a diversity of tropical forest sites. Finally, we highlight areas of
      tropical forest research where notably few data are available, including
      temperature effects on: nutrient cycling, heterotrophic versus autotrophic
      respiration, thermal acclimation versus substrate limitation of plant and
      microbial communities, below-ground C allocation, species composition (plant and
      microbial), and the hydraulic architecture of roots. Whether or not tropical
      forests will become a source or a sink of C in a warmer world remains highly
      uncertain. Given the importance of these ecosystems to the global C budget,
      resolving this uncertainty is a primary research priority.

PMID- 22607309
TI  - Rhodanine as a scaffold in drug discovery: a critical review of its biological
      activities and mechanisms of target modulation.
AB  - INTRODUCTION: Rhodanine-based compounds have been associated with numerous
      biological activities. After many years of research in drug discovery, they have
      gained a reputation as being pan assay interference compounds (PAINS) and
      frequent hitters in screening campaigns. Rhodanine-based compounds are also
      aggregators that can non-specifically interact with target proteins as well as
      Michael acceptors and interfere photometrically in biological assays due to their
      color. AREAS COVERED: The authors review the recently reported biological
      activities of rhodanine-based compounds. Furthermore, the article provides
      details of their synthesis and occurrence in compound libraries through high
      throughput screening (HTS) and virtual high-throughput screening (VHTS).
      Additionally, the authors provide the reader with possible mechanisms of non
      specific target modulation, analysis of the crystal structures of enzyme
      rhodanine complexes and a comparison of rhodanine and thiazolidine-2,4-dione
      moieties. EXPERT OPINION: The biological activity of compounds possessing a
      rhodanine moiety should be considered very critically despite the convincing data
      obtained in biological assays. In addition to the lack of selectivity, unusual
      structure-activity relationship profiles and safety and specificity problems mean
      that rhodanines are generally not optimizable.

PMID- 22607313
TI  - Optimization of fatty alcohol biosynthesis pathway for selectively enhanced
      production of C12/14 and C16/18 fatty alcohols in engineered Escherichia coli.
AB  - BACKGROUND: With the increasing stress from oil price and environmental
      pollution, aroused attention has been paid to the microbial production of
      chemicals from renewable sources. The C12/14 and C16/18 alcohols are important
      feedstocks for the production of surfactants and detergents, which are widely
      used in the most respected consumer detergents, cleaning products and personal
      care products worldwide. Though bioproduction of fatty alcohols has been carried
      out in engineered E. coli, several key problems have not been solved in earlier
      studies, such as the quite low production of C16/18 alcohol, the lack of
      optimization of the fatty alcohol biosynthesis pathway, and the uncharacterized
      performance of the engineered strains in scaled-up system. RESULTS: We improved
      the fatty alcohol production by systematically optimizing the fatty alcohol
      biosynthesis pathway, mainly targeting three key steps from fatty acyl-acyl
      carrier proteins (ACPs) to fatty alcohols, which are sequentially catalyzed by
      thioesterase, acyl-coenzyme A (CoA) synthase and fatty acyl-CoA reductase. By
      coexpression of thioesterase gene BTE, acyl-CoA synthase gene fadD and fatty acyl
      CoA reductase gene acr1, 210.1 mg/L C12/14 alcohol was obtained. A further
      optimization of expression level of BTE, fadD and acr1 increased the C12/14
      alcohol production to 449.2 mg/L, accounting for 75.0% of the total fatty alcohol
      production (598.6 mg/L). In addition, by coexpression of thioesterase gene 'tesA,
      acyl-CoA synthase gene fadD and fatty acyl-CoA reductase gene FAR, 101.5 mg/L
      C16/18 alcohol was obtained, with C16/18 alcohol accounting for 89.2% of the
      total fatty alcohol production. CONCLUSIONS: To our knowledge, this is the first
      report on selective production of C12/14 and C16/18 alcohols by microbial
      fermentation. This work achieved high-specificity production of both C12/14 and
      C16/18 alcohols. The encouraging 598.6 mg/L of fatty alcohols represents the
      highest titer reported so far. In addition, the 101.5 mg/L 89.2% C16/18 alcohol
      suggests an important breakthrough in C16/18 alcohol production. A more detailed
      optimization of the expression level of fatty alcohol biosynthesis pathway may
      contribute to a further improvement of fatty alcohol production.

PMID- 22607314
TI  - Binding-induced fluorescence turn-on assay using aptamer-functionalized silver
      nanocluster DNA probes.
AB  - We present here a binding-induced fluorescence turn-on assay for protein
      detection. Key features of this assay include affinity binding-induced DNA
      hybridization and fluorescence enhancement of silver nanoclusters (Ag NCs) using
      guanine-rich DNA sequences. In an example of an assay for human alpha-thrombin,
      two aptamers (Apt15 and Apt29) were used and were modified by including
      additional sequence elements. A 12-nucleotide (nt) sequence was used to link the
      first aptamer with a nanocluster nucleation sequence at the 5'-end. The second
      aptamer was linked through a complementary sequence (12-nt) to a G-rich overhang
      at the 3'-end. Binding of the two aptamer probes to the target protein initiates
      hybridization between the complementary linker sequences attached to each aptamer
      and thereby bring the end of the G-rich overhang to close proximity to Ag NCs,
      resulting in a significant fluorescence enhancement. With this approach, a
      detection limit of 1 nM and a linear dynamic range of 5 nM-2 MUM were achieved
      for human alpha-thrombin. This fluorescence assay is performed in a single tube,
      and it does not require washing or separation steps. The principle of the binding
      induced DNA hybridization and fluorescence enhancement of Ag NCs can be extended
      to other homogeneous assay applications provided that two appropriate probes are
      available to bind with the same target molecule.

PMID- 22607312
TI  - Exploring the plant-associated bacterial communities in Medicago sativa L.
AB  - BACKGROUND: Plant-associated bacterial communities caught the attention of
      several investigators which study the relationships between plants and soil and
      the potential application of selected bacterial species in crop improvement and
      protection. Medicago sativa L. is a legume crop of high economic importance as
      forage in temperate areas and one of the most popular model plants for
      investigations on the symbiosis with nitrogen fixing rhizobia (mainly belonging
      to the alphaproteobacterial species Sinorhizobium meliloti). However, despite its
      importance, no studies have been carried out looking at the total bacterial
      community associated with the plant. In this work we explored for the first time
      the total bacterial community associated with M. sativa plants grown in mesocosms
      conditions, looking at a wide taxonomic spectrum, from the class to the single
      species (S. meliloti) level. RESULTS: Results, obtained by using Terminal
      Restriction Fragment Length Polymorphism (T-RFLP) analysis, quantitative PCR and
      sequencing of 16 S rRNA gene libraries, showed a high taxonomic diversity as well
      as a dominance by members of the class Alphaproteobacteria in plant tissues.
      Within Alphaproteobacteria the families Sphingomonadaceae and Methylobacteriaceae
      were abundant inside plant tissues, while soil Alphaproteobacteria were
      represented by the families of Hyphomicrobiaceae, Methylocystaceae,
      Bradyirhizobiaceae and Caulobacteraceae. At the single species level, we were
      able to detect the presence of S. meliloti populations in aerial tissues, nodules
      and soil. An analysis of population diversity on nodules and soil showed a
      relatively low sharing of haplotypes (30-40%) between the two environments and
      between replicate mesocosms, suggesting drift as main force shaping S. meliloti
      population at least in this system. CONCLUSIONS: In this work we shed some light
      on the bacterial communities associated with M. sativa plants, showing that
      Alphaproteobacteria may constitute an important part of biodiversity in this
      system, which includes also the well known symbiont S. meliloti. Interestingly,
      this last species was also found in plant aerial part, by applying cultivation
      independent protocols, and a genetic diversity analysis suggested that population
      structure could be strongly influenced by random drift.

PMID- 22607315
TI  - Residential indoor PM2.5 in wood stove homes: follow-up of the Libby changeout
      program.
AB  - In 2005 through 2008, a small rural mountain valley community engaged in a
      woodstove changeout program to address concerns of poor ambient air quality.
      During this program, we assessed changes to indoor air quality before and after
      the introduction of a new, lower emission woodstove. We previously reported a
      >70% reduction in indoor PM(2.5) concentrations in homes following the
      installation of a new Environmental Protection Agency's-certified stove within
      the home. We report here on follow-up of the experiences in these and other homes
      over three winters of sample collection. In 21 homes, we compared pre-changeout
      PM(2.5) concentrations [mean (s.d.) = 45.0 (33.0) MUg/m(3)] to multiple post
      changeout measures of PM(2.5) concentrations using a DustTrak. The mean reduction
      (and 95% confidence interval) from pre-changeout to post-changeout was -18.5
      MUg/m(3) (-31.9, -5.2), adjusting for ambient PM(2.5) , ambient temperature, and
      other factors. Findings across homes and across years were highly variable, and a
      subset of homes did not experience a reduction in PM(2.5) following changeout.
      Reductions were also observed for organic carbon, elemental carbon, and
      levoglucosan, but increases were observed for dehydroabietic acid and abietic
      acid. Despite overall improvements in indoor air quality, the varied response
      across homes may be due to factors other than the introduction of a new
      woodstove. PRACTICAL IMPLICATIONS: Biomass combustion is a common source of
      ambient PM(2.5) in many cold-climate communities. The replacement of older model
      woodstoves with newer technology woodstoves is a potential intervention strategy
      to improve air quality in these communities. In addition to ambient air,
      woodstove changeouts should improve residential indoor air quality. We present
      results from a multi-winter study to evaluate the efficacy of woodstove
      changeouts on improving indoor air quality. Reductions in indoor PM(2.5) were
      evident, but this observation was not consistent across all homes. These findings
      suggest that other factors beyond the introduction of an improved wood burning
      device are relevant to improving indoor air quality in wood burning homes.

PMID- 22607316
TI  - Human HAD phosphatases: structure, mechanism, and roles in health and disease.
AB  - Phosphatases of the haloacid dehalogenase (HAD) superfamily of hydrolases are an
      ancient and very large class of enzymes that have evolved to dephosphorylate a
      wide range of low- and high molecular weight substrates with often exquisite
      specificities. HAD phosphatases constitute approximately one-fifth of all human
      phosphatase catalytic subunits. While the overall sequence similarity between HAD
      phosphatases is generally very low, family members can be identified based on the
      presence of a characteristic Rossmann-like fold and the active site sequence
      DxDx(V/T). HAD phosphatases employ an aspartate residue as a nucleophile in a
      magnesium-dependent phosphoaspartyl transferase reaction. Although there is
      genetic evidence demonstrating a causal involvement of some HAD phosphatases in
      diseases such as cancer, cardiovascular, metabolic and neurological disorders,
      the physiological roles of many of these enzymes are still poorly understood. In
      this review, we discuss the structure and evolution of human HAD phosphatases,
      and summarize their known functions in health and disease.

PMID- 22607317
TI  - HLA-B*40:179, a novel allele identified by sequence-based typing in cord blood
      from a Korean woman.
AB  - The novel allele B*40:179 showed one nucleotide difference with B*40:01:01 in
      exon 4.

PMID- 22607318
TI  - Extracranial-intracranial (EC-IC) bypass of symptomatic middle cerebral artery
      (MCA) total occlusion for haemodynamic impairment patients.
AB  - A retrospective, single-centre, non-randomized study in the management of
      symptomatic middle cerebral artery (MCA) total occlusion disease to evaluate
      extracranial-intracranial (EC-IC) bypass as an intervention for patients with
      atherosclerotic MCA total occlusion, ischemic symptoms (transient ischemic
      attacks [TIAs]) or poor cerebral haemodynamics who had not responded well to
      maximal medical treatment was reported. Twenty-three patients were included in
      the study with the criteria of: having ischemic syndrome, for example, TIA; being
      associated with atherosclerotic MCA total occlusion disease (compatible with
      radiological assessment); being failed to respond to optimal medical therapy
      (e.g. antiplatelet therapy), indicating a repeat TIA or ischemic stroke attack
      was noted during maximal medical therapy; having poor cerebral perfusion on CT
      imaging; and having regional cerebrovascular reactivity (rCVR) of <20% when
      acetazolamide challenge was undergone. Patients had acute ischemic stroke or
      other major medical co-morbidities were excluded. No patient experienced any
      recurrent ischemic stroke during a mean follow-up period of 26.5 months except
      one patient suffered of immediate post-operative ischemic stroke because of the
      temporal vessel being clipped too long and the hypotension caused by anaesthesia.
      Post-operative follow-up imaging, which included MRI (MR angiography) and four
      vessel digital subtraction angiography revealed a 100% patency of superficial
      temporal artery-middle cerebral artery (STA-MCA) anastomosis. No significant
      differences between observation periods (baseline status: 5.46 +/- 5.13/85 +/-
      15; 0.5 month after surgery: 5.18 +/- 5.29/85.91 +/- 15.46 and 3 months after
      surgery: 5.09 +/- 4.75/85.36 +/- 12.27) were found for the neurological
      evaluations of NIHSS and Barthel Index (both expressed in mean +/- SD) in all of
      the 23 patients. The annual risk of recurrent stroke was 0% after EC-IC bypass.
      However, studies with a larger scale are warranted to further confirm the
      effectiveness of EC-IC bypass.

PMID- 22607319
TI  - Photophysical and photodynamical study of fluoroquinolone drug molecule in bile
      salt aggregates.
AB  - Photophysical properties of two widely used antibiotic fluoroquinolone drugs,
      namely Norfloxacin (NOR) and Ofloxacin (OFL) have been investigated in
      biomimicking environments formed by bile salts. Experimental results demonstrate
      that photophysical enhancement and fall of a particular prototropic species are
      sensitive to the excitation wavelength in bile salt aggregates. Excitation at
      shorter wavelengths reveals quenching of fluorescence of these fluoroquinolone
      with addition of sodium deoxycholate (NaDC), sodium taurocholate (NaTC) and
      sodium glycodeoxycholate (NaGDC). On the contrary, we observe a steady increase
      in the fluorescence intensity with a continuous redshift upon excitation at
      longer wavelength. The experimental results were rationalized in terms of the
      fact that, neutral and zwitterionic species of fluoroquinolone molecules in bile
      salt aggregates are selectively excited at shorter wavelength while the cationic
      form of fluoroquinolone molecules are excited at longer wavelength. The excess
      hydronium ions in the hydrophilic surface of bile salt aggregates convert the
      neutral species of NOR and OFL into cationic species causing an enhancement in
      the emission intensity. We found that NaGDC and NaTC because of the conjugate
      head group are more effective in converting the neutral species of
      fluoroquinolones into a cationic species than NaDC. The quenching order is in
      accordance with hydrophobicity indices of bile salt.

PMID- 22607320
TI  - Late gadolinium enhancement by cardiovascular magnetic resonance is complementary
      to left ventricle ejection fraction in predicting prognosis of patients with
      stable coronary artery disease.
AB  - BACKGROUND: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance
      (CMR) predicts adverse prognosis in patients with stable coronary artery disease
      (CAD). However, the interaction with conventional risk factors remains uncertain.
      Our aim was to assess whether the extent of LGE is an independent predictor of
      adverse cardiac outcome beyond conventional risk factors, including left
      ventricle ejection fraction (LVEF). METHODS: We enrolled 376 patients (88% males,
      64 +/- 11 years) with stable CAD, who underwent LGE assessment and a detailed
      conventional evaluation (clinical and pharmacological history, risk factors, ECG,
      Echocardiography). During a follow-up of 38 +/- 21 months, 56 events occurred (32
      deaths, 24 hospitalizations for heart failure). RESULTS: LGE and LVEF showed the
      strongest univariate associations with end-points (HR: 13.61 [95%C.I.: 7.32
      25.31] for LGE >= 45% of LV mass; and 12.34 [6.80-22.38] for LVEF <= 30%; p <
      0.0001). Multivariate analysis identified baseline LVEF, loop diuretic therapy,
      moderate-severe mitral regurgitation and pulmonary hypertension as significant
      predictors among conventional risk factors. According to a step-wise approach,
      LGE showed strong association with prognosis as well (5.25 [2.64-10.43]; p <
      0.0001). LGE significantly improved the model predictability (chi-square 239 vs
      221, F-test p < 0.0001) with an additive effect on the prognostic power of LVEF,
      which however retained its prognostic power (4.89 [2.50-09.56]; p < 0.0001).
      Patients with LGE >= 45% and/or LVEF <= 30% had much worse prognosis compared to
      patients without risk factors (annual event rates of 43% vs 3%; p < 0.0001).
      Interestingly LGE was a significant predictor when all cause mortality was
      analyzed as the only endpoint. CONCLUSIONS: This study demonstrates that LGE
      assessed by CMR is a robust independent non-invasive marker of prognosis in
      stable CAD patients. LGE can integrate the available metrics to substantially
      improve risk stratification.

PMID- 22607321
TI  - Wnt5a inhibits the CpG oligodeoxynucleotide-triggered activation of human
      plasmacytoid dendritic cells.
AB  - Plasmacytoid dendritic cells (pDCs) fulfil multiple roles in immunity, and can
      secrete large amounts of interferon (IFN)-alpha. However, the available evidence
      suggests that they may actually counteract efficient antitumour immunity. Thus in
      melanoma, pDCs are abundant, but they are anergic and deficient in IFN-alpha
      secretion. pDC anergy is thought to be caused by immunosuppressive factors
      secreted by melanoma cells. One factor strongly expressed by melanoma is Wnt5a,
      which is implicated in cancer tissue invasion. In this paper, we show that Wnt5a
      is able to block the upregulation of the activation markers CD80 and CD86 on
      naive human pDCs stimulated by CpG oligodeoxynucleotide, and CpG-triggered
      secretion of IFN-alpha by pDCs. Our results suggest that Wnt5a may not only
      initiate cancer invasion, but could also regulate activation of pDC. These data
      provide a clear rationale to investigate a role for Wnt5a in immune regulation.

PMID- 22607322
TI  - The antimicrobial effect of new and conventional endodontic irrigants on intra
      orally infected dentin.
AB  - OBJECTIVES: To evaluate if the incorporation of antimicrobial compounds to
      chelating agents or the use of chelating agents with antimicrobial activity as 7%
      maleic acid and peracetic acid show similar disinfection ability in comparison to
      conventional irrigants as sodium hypochlorite or iodine potassium iodide against
      biofilms developed on dentin. MATERIALS AND METHODS: The total bio-volume of live
      cells, the ratio of live cells and the substratum coverage of dentin infected
      intra-orally and treated with the irrigant solutions: MTAD, Qmix, Smear Clear, 7%
      maleic acid, 2% iodine potassium iodide, 4% peracetic acid, 2.5% and 5.25% sodium
      hypochlorite was measured by using confocal microscopy and the live/dead
      technique. Five samples were used for each irrigant solution. RESULTS: Several
      endodontic irrigants containing antimicrobials as clorhexidine (Qmix), cetrimide
      (Smear Clear), maleic acid, iodine compounds or antibiotics (MTAD) lacked an
      effective antibiofilm activity when the dentin was infected intra-orally. The
      irrigant solutions 4% peracetic acid and 2.5-5.25% sodium hypochlorite decrease
      significantly the number of live bacteria in biofilms, providing also cleaner
      dentin surfaces (p < 0.05). CONCLUSIONS: Several chelating agents containing
      antimicrobials could not remove nor kill significantly biofilms developed on
      intra-orally infected dentin, with the exception of sodium hypochlorite and 4%
      peracetic acid. Dissolution ability is mandatory for an appropriate eradication
      of biofilms attached to dentin.

PMID- 22607323
TI  - Subclinical ultrasonographic abnormalities of the suspensory ligament branch of
      the athletic horse: A survey of 60 Thoroughbred racehorses.
AB  - REASONS FOR PERFORMING STUDY: Ultrasonographic (US) abnormalities of the
      suspensory ligament branch (SLB) have been poorly investigated but can have
      considerable impact on market value and career path when encountered in athletic
      horses. There is a need for determination of the prevalence and relationship to
      clinical injury of these US abnormalities in the Thoroughbred (TB) racehorse.
      OBJECTIVES: To establish the prevalence of, and the repeatability of an US
      grading system for, subclinical US abnormalities of the forelimb SLB in a
      population of UK TB flat racehorses. METHODS: Ultrasonographic assessment of the
      forelimb SLBs of 60 TB racehorses free from history and clinical indication of
      SLB desmopathy in a single UK training yard was performed. Images were viewed
      independently by 2 blinded observers and graded for US abnormality. Interobserver
      agreement was assessed using Cohen's kappa statistic with 95% confidence
      intervals (95% CI). RESULTS: Prevalence of horses with subclinical US abnormality
      of the forelimb SLB of moderate severity was 6.7%. Medial branches were
      overrepresented. Inter observer agreement was substantial for US grade (kappa =
      0.743; 95% CI 0.652-0.834) and almost perfect for appearance of sesamoid bone at
      ligament insertion (kappa = 0.817; 95% CI 0.66-0.98). CONCLUSIONS: The study
      reveals that a proportion of TB racehorses in flat training free from history or
      clinical signs of SLB injury have US abnormalities that could negatively impact
      on market value and career path. POTENTIAL RELEVANCE: Clinicians should be aware
      that US abnormalities of the SLB may not always be related to clinical
      desmopathy. Further longitudinal studies are required to determine whether such
      findings are predictive for future injury.

PMID- 22607324
TI  - A national study of socioeconomic status and tuberculosis rates by country of
      birth, United States, 1996-2005.
AB  - BACKGROUND: Tuberculosis (TB) in developed countries has historically been
      associated with poverty and low socioeconomic status (SES). In the past quarter
      century, TB in the United States has changed from primarily a disease of native
      born to primarily a disease of foreign-born persons, who accounted for more than
      60% of newly-diagnosed TB cases in 2010. The purpose of this study was to assess
      the association of SES with rates of TB in U.S.-born and foreign-born persons in
      the United States, overall and for the five most common foreign countries of
      origin. METHODS: National TB surveillance data for 1996-2005 was linked with ZIP
      Code-level measures of SES (crowding, unemployment, education, and income) from
      U.S. Census 2000. ZIP Codes were grouped into quartiles from low SES to high SES
      and TB rates were calculated for foreign-born and U.S.-born populations in each
      quartile. RESULTS: TB rates were highest in the quartiles with low SES for both
      U.S.-born and foreign-born populations. However, while TB rates increased five
      fold or more from the two highest to the two lowest SES quartiles among the U.S.
      born, they increased only by a factor of 1.3 among the foreign-born. CONCLUSIONS:
      Low SES is only weakly associated with TB among foreign-born persons in the
      United States. The traditional associations of TB with poverty are not sufficient
      to explain the epidemiology of TB among foreign-born persons in this country and
      perhaps in other developed countries. TB outreach and research efforts that focus
      only on low SES will miss an important segment of the foreign-born population.

PMID- 22607325
TI  - Transarticular facet screw stabilization and dorsal laminectomy in 26 dogs with
      degenerative lumbosacral stenosis with instability.
AB  - OBJECTIVE: To describe outcome after transarticular facet screw stabilization and
      dorsal laminectomy for treatment of dynamic degenerative lumbosacral stenosis
      (DLS) in 26 dogs. STUDY DESIGN: Retrospective case series. ANIMALS: Dogs (n = 26)
      with dynamic DLS. METHODS: Medical records (2004-2009) of dogs treated with
      transarticular facet screw stabilization and dorsal laminectomy were reviewed.
      Dogs (n = 26) were available for immediate postoperative follow-up, 21 dogs at 6
      weeks, and 15 at greater than 6 months. Dogs were evaluated by radiographic
      assessment and owner questionnaire. Lumbosacral (LS) intervertebral disc (IVD)
      spaces were measured on pre and postoperative 6-week and 6-month radiographs.
      RESULTS: In 23 dogs, improvement in clinical signs occurred within 7 days of
      surgery. Overall postsurgical complication rate directly related to the surgical
      procedure was 15.4%. LS IVD space measurements taken immediately postoperatively,
      at 6 weeks, and >= 6 months were all significantly increased compared with
      preoperative measurements. All working dogs (4) returned to full work within 14
      months. Most owners (85%) reported their dog was ambulating normally at 6 months
      with no perceptible lameness during normal activity. All owners perceived their
      dog's ability to walk, run, and jump after surgery to be improved. CONCLUSIONS:
      Transarticular facet screw stabilization and dorsal laminectomy maintains
      distraction of the LS IVD space for medium-to-large breed dogs with dynamic DLS
      with a high degree of owner satisfaction, and is comparable to other reported
      surgical techniques for DLS.

PMID- 22607326
TI  - Estimation of groundwater residence time using environmental radioisotopes
      (14C,T) in carbonate aquifers, southern Poland.
AB  - Triassic carbonate aquifers in the Upper Silesia region, affected by intense
      withdrawal, have been investigated by means of isotopic analyses of (14)C,
      delta(13)C, delta(2)H, delta(18)O and (3)H. The isotopic examinations were
      carried out in the 1970s and in the early 1980s, and it was the first application
      of tracers to estimate age and vulnerability for the contamination of groundwater
      in this region. Similar isotopic analyses were conducted in 2007 and 2008 with
      the same Triassic carbonate formation. The isotopic examinations were performed
      within the confined part of the carbonate formation, wherein aquifers are covered
      by semi-permeable deposits. The direct recharge of the aquifer occurs in the
      outcrop areas, but it mainly takes place due to percolation of the water through
      aquitards and erosional windows. The Triassic aquifer has been intensively
      drained by wells and by lead-zinc mines. Nowadays, the declining water demand and
      closure of some mines have induced a significant increase in the water table
      level. The detailed analysis of the results, including the radiocarbon age
      corrections and the comparison of radioisotope activities, has made it possible
      to estimate the range of residence time within the carbonate Triassic aquifer.
      This range from several tens to several tens of thousands indicates that the
      recharge of aquifers might have occurred between modern times and the
      Pleistocene. The apparent age of the water estimated on the basis of (14)C
      activity was corrected considering the carbon isotope exchange and the diffusion
      between mobile water in fractures and stagnant water in micropores. The obtained
      corrected period of recharge corresponds to the result of investigations of noble
      gases, which were carried out in the 1990s. In almost half of the cases,
      groundwater is a mixture of young and old water. The mixing processes occur
      mainly in areas of heavy exploitation of the aquifer.

PMID- 22607327
TI  - Sleep restriction and emotion, electroencephalography (EEG) and dream recall, and
      insomnia and punctuality.

PMID- 22607328
TI  - Highlights of the 1st IEEE Symposium on Biological Data Visualization.

PMID- 22607329
TI  - Cluster analysis of host cytokine responses to biodefense pathogens in a whole
      blood ex vivo exposure model (WEEM).
AB  - BACKGROUND: Rapid detection and therapeutic intervention for infectious and
      emerging diseases is a major scientific goal in biodefense and public health.
      Toward this end, cytokine profiles in human blood were investigated using a human
      whole blood ex vivo exposure model, called WEEM. RESULTS: Samples of whole blood
      from healthy volunteers were incubated with seven pathogens including Yersinia
      pseudotuberculosis, Yersinia enterocolitica, Bacillus anthracis, and multiple
      strains of Yersinia pestis, and multiplexed protein expression profiling was
      conducted on supernatants of these cultures with an antibody array to detect 30
      cytokines simultaneously. Levels of 8 cytokines, IL-1alpha, IL-1beta, IL-6, IL-8,
      IL-10, IP-10, MCP-1 and TNFalpha, were significantly up-regulated in plasma after
      bacterial exposures of 4 hours. Statistical clustering was applied to group the
      pathogens based on the host response protein expression profiles. The nearest
      phylogenetic neighbors clustered more closely than the more distant pathogens,
      and all seven pathogens were clearly differentiated from the unexposed control.
      In addition, the Y. pestis and Yersinia near neighbors were differentiated from
      the B. anthracis strains. CONCLUSIONS: Cluster analysis, based on host response
      cytokine profiles, indicates that distinct patterns of immunomodulatory proteins
      are induced by the different pathogen exposures and these patterns may enable
      further development into biomarkers for diagnosing pathogen exposure.

PMID- 22607332
TI  - Identification of a novel HLA-DPB1 allele, DPB1*138:01, by sequence-based typing.
AB  - The new allele differs from HLA-DPB1*23:01 in exon 3.

PMID- 22607330
TI  - Early sucking and swallowing problems as predictors of neurodevelopmental outcome
      in children with neonatal brain injury: a systematic review.
AB  - AIM: Early sucking and swallowing problems may be potential markers of neonatal
      brain injury and assist in identifying those infants at increased risk of adverse
      outcomes, but the relation between early sucking and swallowing problems and
      neonatal brain injury has not been established. The aim of the review was,
      therefore, to investigate the relation between early measures of sucking and
      swallowing and neurodevelopmental outcomes in infants diagnosed with neonatal
      brain injury and in infants born very preterm (<32wks) with very low birthweight
      (<1500g), at risk of neonatal brain injury. METHOD: We conducted a systematic
      review of English-language articles using CINAHL, EMBASE, and MEDLINE OVID (from
      1980 to May 2011). Additional studies were identified through manual searches of
      key journals and the works of expert authors. Extraction of data informed an
      assessment of the level of evidence and risk of bias for each study using a
      predefined set of quality indicators. RESULTS: A total of 394 abstracts were
      generated by the search but only nine studies met the inclusion criterion. Early
      sucking and swallowing problems were present in a consistent proportion of
      infants and were predictive of neurodevelopmental outcome in infancy in five of
      the six studies reviewed. LIMITATIONS: The methodological quality of studies was
      variable in terms of research design, level of evidence (National Health and
      Medical Research Council levels II, III, and IV), populations studied,
      assessments used and the nature and timing of neurodevelopmental follow-up.
      CONCLUSIONS: Based upon the results of this review, there is currently
      insufficient evidence to clearly determine the relation between early sucking and
      swallowing problems and neonatal brain injury. Although early sucking and
      swallowing problems may be related to later neurodevelopmental outcomes, further
      research is required to delineate their value in predicting later motor outcomes
      and to establish reliable measures of early sucking and swallowing function.

PMID- 22607333
TI  - Interspecies competition and inhibition within the oral microbial flora:
      environmental factors influence the inhibition of Streptococcus mutans by
      Streptococcus oligofermentans.
AB  - Dental caries is a bacterial infectious disease. Streptococcus mutans is the
      primary pathogen that causes dental caries. Streptococcus oligofermentans is a
      new oral streptococcal species that can inhibit the growth of S. mutans
      specifically. The study aimed to assess the inhibition of S. mutans by S.
      oligofermentans under different oral environmental conditions. The inhibition
      under different carbohydrate and oxygen conditions was investigated in vitro
      using an interspecies interaction assay. The 4-aminoantipyine (4-ATTP) method was
      used to measure the yield and the initial production rate of H(2) O(2) in S.
      oligofermentans. The inhibitory effect was enhanced when the bacteria were
      cultured with carbohydrates and under aerobic conditions, or when S.
      oligofermentans was inoculated earlier than S. mutans. The initial synthesis
      rates of H(2) O(2) by S. oligofermentans were higher in the presence of
      carbohydrates and in aerobic culture conditions. In terms of the total H(2) O(2)
      yield, the effect of the environmental conditions was as follows: no
      carbohydrates > sucrose> glucose, and aerobic conditions > anaerobic conditions.
      We conclude that the presence of carbohydrate and oxygen significantly affect the
      ability of S. oligofermentans to inhibit the growth of S. mutans. The difference
      in inhibitory effect may be attributed to changes in the capacity of S.
      oligofermentans to produce H(2) O(2) .

PMID- 22607335
TI  - Jaw-movement smoothness during empty chewing and gum chewing.
AB  - A major goal of motor coordination is the production of a smooth movement. Jerk
      cost, which is an inverse measure of movement smoothness, has been evaluated
      during gum chewing in previous studies. However, the effect of the gum bolus is
      still unclear. The aims of this study were to compare the jerk-cost values of
      normal gum chewing with those of empty chewing. Thirteen subjects undertook,
      empty chewing, then chewing of gum, and then a second empty chewing. Jerk-cost
      was calculated from an accelerometer attached to the skin of the mentum. There
      was a significantly higher smoothness (i.e. lower jerk-cost, P < 0.05) during the
      opening and second-half closing phases in empty chewing compared with gum
      chewing. There were no significant differences in jerk-costs (i.e. opening or
      closing) between the first and the second empty-chewing sequences. These results
      suggest that the influence of the mechanical effects of tooth contact on jerk
      cost is not restricted just to the occlusal phase of chewing, but rather the
      effect influences the entire opening and closing phases of chewing.

PMID- 22607334
TI  - Titanium alloy surface oxide modulates the conformation of adsorbed fibronectin
      to enhance its binding to alpha(5) beta(1)  integrins in osteoblasts.
AB  - Our laboratory has previously demonstrated that heat (600 degrees C) or
      radiofrequency plasma glow discharge (RFGD) pretreatment of a titanium alloy
      (Ti6Al4V) increased the net negative charge of the alloy's surface oxide and the
      attachment of osteoblastic cells to adsorbed fibronectin. The purpose of the
      current study was to investigate the biological mechanism by which these surface
      pretreatments enhance the capacity of fibronectin to stimulate osteoblastic cell
      attachment. Each pretreatment was found to increase the binding (measured by
      ELISA) of a monoclonal anti-fibronectin Ig to the central integrin-binding domain
      of adsorbed fibronectin, and to increase the antibody's inhibition of osteogenic
      cell attachment (measured by hexosaminidase assay). Pretreatments also increased
      the binding (measured by ELISA) of anti-integrin IgG's to the alpha(5) and
      beta(1) integrin subunits that became attached to fibronectin during cell
      incubation. These findings suggest that negatively charged surface oxides of
      Ti6Al4V cause conformational changes in fibronectin that increase the
      availability of its integrin-binding domain to alpha(5) beta(1) integrins.

PMID- 22607336
TI  - Cone beam computed tomography evaluations of marginal alveolar bone before and
      after orthodontic treatment combined with premolar extractions.
AB  - Using cone beam computed tomography (CBCT) we investigated the distance between
      the cemento-enamel junction (CEJ) and the marginal bone crest (MBC) at buccal,
      lingual, mesial, and distal surfaces of incisors to first molars in adolescents
      before (baseline) and after extractive orthodontic treatment (study end point).
      Patients with Class I malocclusion, crowding and an overjet of <= 5 mm were
      examined with a CBCT unit using a 60 * 60-mm field of view and a 0.125-mm voxel
      size. Large differences in marginal bone height were found at baseline,
      particularly between tooth surfaces. There was a slight correlation between age
      and CEJ-MBC distance. From baseline to the study end point, large bone-height
      changes among teeth and tooth surfaces could be seen. Lingual surfaces, followed
      by buccal surfaces, showed the largest changes. Eighty-four per cent of lingual
      surfaces of mandibular central incisors exhibited a bone-height decrease of > 2
      mm. The bone-height decrease was larger at lingual surfaces in the mandible than
      in the maxilla, and larger in girls (mean=1.8 mm) than in boys (mean=1.5 mm).
      Fewer than 1% of proximal surfaces exhibited changes of > 2 mm. It is unknown
      whether the changes in marginal bone height are transitory. A high-quality CBCT
      technique may help to determine this by providing a deeper insight into the long
      term side effects of orthodontic treatment.

PMID- 22607337
TI  - Association between subjective oral health and regularity of service use.
AB  - The aim was to evaluate the predictive power of two different measures of
      subjective oral health in relation to regularity of use of oral health-care
      services. The nationally representative data were collected as part of the Health
      2000 Survey on Finnish adults, 30+ yr of age (n=4926). Subjective oral health and
      regularity of using of oral health-care services were measured using single
      questions and oral health-related quality of life was measured using the 14-item
      Oral Health Impact Profile (OHIP-14) questionnaire. Those reporting poor oral
      health or higher impacts in the OHIP-14 were more likely to be irregular users of
      oral health-care services. Further research is needed to investigate more
      precisely the applicability of these measures in different settings of oral
      health-care provision.

PMID- 22607338
TI  - Development of the Chinese version of the Dentine Hypersensitivity Experience
      Questionnaire.
AB  - The aim of this study was to evaluate the reliability and the validity of the
      Chinese version of the Dentine Hypersensitivity Experience Questionnaire (DHEQ).
      After translation and cross-cultural adaptation following international
      guidelines, 110 patients with dentine hypersensitivity were recruited to complete
      the questionnaire. The reliability of the Chinese version of the DHEQ was
      evaluated using internal consistency and test-retest methods. Construct validity
      was determined based on factor analysis, discriminative validity (by comparing
      the subscale scores difference in the degree of sensitivity being investigated),
      and convergent validity (by analyzing the correlation between DHEQ subscale
      scores and the global rating of oral health question). Cronbach's alpha value
      (internal reliability) for the total DHEQ score was 0.95 and the intraclass
      correlation coefficient (ICC) value (test-retest reliability) was 0.85. Construct
      validity was determined by factor analysis, extracting eight factors, accounting
      for 74% of the variance. All items had factor loadings of >0.40. In addition, the
      Chinese version of the DHEQ was found to be valid for distinguishing patients
      with varying degrees of dentine hypersensitivity. In terms of convergent
      validity, the impact scale was significantly highly correlated to the global oral
      health rating. The results suggest that the Chinese version of the DHEQ has
      satisfactory psychometric properties and is applicable for patients with dentine
      hypersensitivity in China.

PMID- 22607339
TI  - Difficulties in emotional regulation: association with poorer oral health-related
      quality of life in the general population.
AB  - Personality is one of the strongest predictors of subjective well-being and may,
      according to a few previous studies, affect how people report oral health-related
      quality of life (OHRQoL). Alexithymia, a personality trait involving difficulties
      in emotional regulation, is associated with poorer health-related quality of life
      in the general population. We studied if alexithymia is also associated with
      poorer OHRQoL in a general population sample of 4,460 adults. Oral health-related
      quality of life was measured using the 14-item Oral Health Impact Profile (OHIP
      14) and alexithymia was measured using the 20-item Toronto Alexithymia Scale (TAS
      20). Controlling for clinically assessed dental health, depression, anxiety, and
      socio-demographic variables, higher scores on the TAS-20 as well as on its three
      dimensions [difficulties in identifying feelings (DIF), difficulties in
      describing feelings (DDF), and externally oriented thinking (EOT)] were
      associated with higher OHIP-14 composite scores according to Poisson regression
      analyses. In adjusted logistic regression analyses, the TAS-20 and two of its
      dimensions (DIF and DDF) were positively and significantly associated with the
      seven OHIP-14 dimensions and the prevalence of those reporting one or more OHIP
      14 items fairly often or very often. The study showed that difficulties in
      emotional regulation might be reflected in poorer OHRQoL, regardless of the
      dental health status, depression, anxiety, and socio-demographic variables.

PMID- 22607340
TI  - Oral health -- not a priority issue a grounded theory analysis of barriers for
      young patients with disabilities to receive oral health care on the same premise
      as others.
AB  - Oral health problems are reported more frequently in children with disabilities,
      but the reasons for this are not fully known. The present study was conducted to
      illuminate and to gain a deeper understanding of the possible barriers preventing
      children with disabilities from receiving oral health care on the same premise as
      others. Transcribed in-depth interviews with 65 informants (14 parents, 18 dental
      health-care professionals, 17 medical health-care professionals, and 16
      individuals with disabilities) were analysed in open, axial, and selective coding
      processes according to Grounded Theory. The results showed that no-one seems to
      take an overriding responsibility for the oral health of young patients with
      disabilities. This was described in a formal theory showing that defective
      knowledge about importance of oral health, limited ability to focus on oral
      health, and uncertainty in treating the unknown in patients, family, and dental
      and medical health-care professionals result in a situation in which oral health
      is left out in young patients with disabilities; it is not a priority issue.

PMID- 22607341
TI  - Influence of preliminary etching on the stability of bonds created by one-step
      self-etch bonding systems.
AB  - We evaluated the effects of preliminary etching of dentine on the stability of
      the bond created by one-step self-etch adhesives under different storage
      conditions. Adper Easy Bond (3M ESPE) and iBond Self-Etch (iBond SE; Heraeus
      Kulzer) were applied with an etch-and-rinse (i.e. after preliminary phosphoric
      acid etching for 15 s) or a self-etch approach. Resin-dentine bonded specimens
      were sectioned perpendicularly to the adhesive interface according to the 'non
      trimming technique'. Beams were stored in artificial saliva for 24 h, 6 months,
      or 1 yr at 37 degrees C, or in 10% NaOCl for 5 h at room temperature, and then
      stressed until failure; the microtensile bond strengths were calculated.
      Interfacial nanoleakage of additional teeth was evaluated using light microscopy
      or transmission electron microscopy. Adper Easy Bond showed higher bond strength
      than iBond SE, regardless of the dentine treatment. Similar microtensile bond
      strength results were obtained for teeth subjected to artificial ageing in 10%
      NaOCl for 5 h at room temperature and for teeth stored in artificial saliva for 6
      months at 37 degrees C. The additional etching step increased the microtensile
      bond strength for Adper Easy Bond and iBond SE. This study supports the use of
      one-step adhesives on etched dentine because of the increased bond strength
      compared with their application onto smear-layer-covered dentine, regardless of
      storage conditions.

PMID- 22607342
TI  - Influence of grain size and veneer firing process on the flexural strength of
      zirconia ceramics.
AB  - The aim of the present investigation was to study the influence of grain size on
      the strength of yttria-stabilized zirconia upon exposure to an additional heat
      treatment, mimicking the veneering process. The green bodies of zirconia discs
      prepared by cold isostatic pressing were sintered at 1,425, 1,500, or 1,575
      degrees C to customize the grain size. The disc-shaped specimens were highly
      polished and then processed with or without additional heat treatments (five
      times at 850-930 degrees C). Ten specimens from each treatment group were
      subjected to a biaxial flexural strength test according to the ISO 6872 standard.
      The grain size of the specimens was analyzed by the mean linear intercept
      technique using scanning electron microscopy. It was demonstrated that the
      mechanical strength of zirconia ceramics was not reduced by the veneer firing
      processes when polished specimens were used, but the strength was found to
      decrease with increasing grain size. The raw materials and the sintering process
      used should be selected appropriately to avoid grain coarsening because it was
      found that the strength was influenced by large grains.

PMID- 22607343
TI  - Resonance frequency analysis: a new diagnostic tool for dental ankylosis.
AB  - Ankylosed teeth are considered in orthodontic treatment planning; however,
      diagnostic tools to quantify the rigidity of the tooth-to-bone connection are
      rare. Resonance frequency analysis (RFA) can quantify the rigidity of the dental
      implant-to-bone connection and thus may serve as a potential diagnostic tool to
      identify ankylosed teeth. To test this assumption, we examined 15 and 30 primary
      mandibular molars, with and without clinical signs of ankylosis, using the
      Osstell Mentor system. A cut-off implant stability quotient (ISQ) of 43 provided
      a specificity of 100% and a sensitivity of 53.3% when measured in the mesio
      distal direction or a sensitivity of 20% when measured in the bucco-lingual
      direction. Based on a receiver-operating characteristic (ROC), the area under the
      curve (AUC) of 0.807 showed the mesio-distal direction of measurement to be a
      test of moderate discriminatory power. Given its non-invasiveness, RFA may serve
      as a quantitative diagnostic supplement to the clinical examination of
      potentially ankylosed primary molars.

PMID- 22607344
TI  - Inadequate description of educational interventions in ongoing randomized
      controlled trials.
AB  - BACKGROUND: The registration of clinical trials has been promoted to prevent
      publication bias and increase research transparency. Despite general agreement
      about the minimum amount of information needed for trial registration, we lack
      clear guidance on descriptions of non-pharmacologic interventions in trial
      registries. We aimed to evaluate the quality of registry descriptions of non
      pharmacologic interventions assessed in ongoing randomized controlled trials
      (RCTs) of patient education. METHODS: On 6 May 2009, we searched for all ongoing
      RCTs registered in the 10 trial registries accessible through the World Health
      Organization International Clinical Trials Registry Platform. We included trials
      evaluating an educational intervention (that is, designed to teach or train
      patients about their own health) and dedicated to participants, their family
      members or home caregivers. We used a standardized data extraction form to
      collect data related to the description of the experimental intervention, the
      centers, and the caregivers. RESULTS: We selected 268 of 642 potentially eligible
      studies and appraised a random sample of 150 records. All selected trials were
      registered in 4 registers, mainly ClinicalTrials.gov (61%). The median
      [interquartile range] target sample size was 205 [100 to 400] patients. The
      comparator was mainly usual care (47%) or active treatment (47%). A minority of
      records (17%, 95% CI 11 to 23%) reported an overall adequate description of the
      intervention (that is, description that reported the content, mode of delivery,
      number, frequency, duration of sessions and overall duration of the
      intervention). Further, for most reports (59%), important information about the
      content of the intervention was missing. The description of the mode of delivery
      of the intervention was reported for 52% of studies, the number of sessions for
      74%, the frequency of sessions for 58%, the duration of each session for 45% and
      the overall duration for 63%. Information about the caregivers was missing for
      70% of trials. Most trials (73%) took place in the United States or United
      Kingdom, 64% involved only one centre, and participating centers were mainly
      tertiary-care, academic or university hospitals (51%). CONCLUSIONS: Educational
      interventions assessed in ongoing RCTs of educational interventions are poorly
      described in trial registries. The lack of adequate description raises doubts
      about the ability of trial registration to help patients and researchers know
      about the treatment evaluated in trials of education.

PMID- 22607345
TI  - High-throughput and parallel SNP discovery in selected candidate genes in
      Eucalyptus camaldulensis using Illumina NGS platform.
AB  - Next generation sequencing (NGS) technologies have revolutionized the pace and
      scale of genomics- and transcriptomics-based SNP discovery across different plant
      and animal species. Herein, 72-base paired-end Illumina sequencing was employed
      for high-throughput, parallel and large-scale SNP discovery in 41 growth-related
      candidate genes in Eucalyptus camaldulensis. Approximately 100 kb of genome from
      96 individuals was amplified and sequenced using a hierarchical DNA/PCR pooling
      strategy and assembled over corresponding E. grandis reference. A total of 1191
      SNPs (minimum 5% other allele frequency) were identified with an average
      frequency of 1 SNP/83.9 bp, whereas in exons and introns, it was 1 SNP/108.4 bp
      and 1 SNP/65.6 bp, respectively. A total of 75 insertions and 89 deletions were
      detected of which approximately 15% were exonic. Transitions (Tr) were in excess
      than transversions (Tv) (Tr/Tv: 1.89), but exceeded in exons (Tr/Tv: 2.73). In
      exons, synonymous SNPs (Ka) prevailed over the non-synonymous SNPs (Ks; average
      Ka/Ks ratio: 0.72, range: 0-3.00 across genes). Many of the exonic SNPs/indels
      had potential to change amino acid sequence of respective genes. Transcription
      factors appeared more conserved, whereas enzyme coding genes appeared under
      relaxed control. Further, 541 SNPs were classified into 196 'equal frequency'
      (EF) blocks with almost similar minor allele frequencies to facilitate selection
      of one tag-SNP/EF-block. There were 241 (approximately 20%) 'zero-SNP' blocks
      with absence of SNPs in surrounding +/-60 bp windows. The data thus indicated
      enormous extant and unexplored diversity in E. camaldulensis in the studied genes
      with potential applications for marker-trait associations.

PMID- 22607346
TI  - Understanding efflux in Gram-negative bacteria: opportunities for drug discovery.
AB  - INTRODUCTION: Bacteria evolved an arsenal of mechanisms to deal with toxic
      compounds and metabolic stresses, including antimicrobial agents. Efflux pumps
      are major players in the multidrug resistance of Gram-negative bacteria and pose
      major hurdles in the drug discovery process. However, recent advances in our
      understanding of efflux in these bacteria provide opportunities and assets for
      drug discovery. AREAS COVERED: This review provides an overview of drug efflux in
      Gram-negative bacteria and its role in antimicrobial resistance, stress responses
      and other biological processes such as biofilm formation, and virulence. The
      discussion includes comments on the significance of synergy between a low
      permeability outer membrane and efflux, notably the role of porins and
      lipopolysaccharide. The author then summarizes efforts aimed at inhibiting efflux
      pumps as a means to extend the utility of clinically useful antibiotics. This
      includes highlights of identification and characterization of small molecule
      efflux pump inhibitors (EPIs) from natural and synthetic sources, as well as
      novel strategies such as gene silencing and inhibitory antibodies. EXPERT
      OPINION: Options for treating infections caused by multidrug-resistant bacteria
      are limited. Given the attractiveness of the therapeutic potential of efflux pump
      inhibition, further studies exploring novel strategies to interfere with efflux
      pump expression and function are warranted. This includes rational EPI design
      facilitated by pump structure information, exploitation of genetically defined
      efflux-proficient and efflux-compromised strain panels and non-traditional
      approaches such as pump inhibition by gene silencing, antibodies and perhaps even
      phage.

PMID- 22607347
TI  - Tetramerization of human guanylate-binding protein 1 is mediated by coiled-coil
      formation of the C-terminal alpha-helices.
AB  - The human guanylate-binding protein 1 (hGBP1) is a large GTP-binding protein
      belonging to the dynamin family, a common feature of which is nucleotide
      dependent assembly to homotypic oligomers. Assembly leads to stimulation of
      GTPase activity, which, in the case of dynamin, is responsible for scission of
      vesicles from membranes. By yeast two-hybrid and biochemical experiments we
      addressed intermolecular interactions between all subdomains of hGBP1 and
      identified the C-terminal subdomain, alpha12/13, as a new interaction site for
      self-assembly. alpha12/13 represents a stable subdomain of hGBP1, as shown by CD
      spectroscopy. In addition to contacts between GTPase domains leading to dimer
      formation, the interaction between two alpha12/13 subdomains, in the course of
      GTP hydrolysis, results in tetramer formation of the protein. With the help of CD
      spectroscopy we showed coiled-coil formation of two alpha12/13 subdomains and
      concentration-dependent measurements allow estimating a value for the
      dissociation constant of 7.3 MUM. We suggest GTP hydrolysis-driven release of the
      alpha12/13 subdomain, making it available for coiled-coil formation. Furthermore,
      we can demonstrate the biological relevance of hGBP1 tetramer formation in living
      cells by chemical cross-link experiments.

PMID- 22607348
TI  - Characterizing the spatial and temporal variation of malaria incidence in
      Bangladesh, 2007.
AB  - BACKGROUND: Malaria remains a significant health problem in Bangladesh affecting
      13 of 64 districts. The risk of malaria is variable across the endemic areas and
      throughout the year. A better understanding of the spatial and temporal patterns
      in malaria risk and the determinants driving the variation are crucial for the
      appropriate targeting of interventions under the National Malaria Control and
      Prevention Programme. METHODS: Numbers of Plasmodium falciparum and Plasmodium
      vivax malaria cases reported by month in 2007, across the 70 endemic thanas (sub
      districts) in Bangladesh, were assembled from health centre surveillance reports.
      Bayesian Poisson regression models of incidence were constructed, with fixed
      effects for monthly rainfall, maximum temperature and elevation, and random
      effects for thanas, with a conditional autoregressive prior spatial structure.
      RESULTS: The annual incidence of reported cases was 34.0 and 9.6 cases/10,000
      population for P. falciparum and P. vivax respectively and the population of the
      70 malaria-endemic thanas was approximately 13.5 million in 2007. Incidence of
      reported cases for both types of malaria was highest in the mountainous south
      east of the country (the Chittagong Hill Tracts). Models revealed statistically
      significant positive associations between the incidence of reported P. vivax and
      P. falciparum cases and rainfall and maximum temperature. CONCLUSIONS: The risk
      of P. falciparum and P. vivax was spatially variable across the endemic thanas of
      Bangladesh and also highly seasonal, suggesting that interventions should be
      targeted and timed according to the risk profile of the endemic areas. Rainfall,
      temperature and elevation are major factors driving the spatiotemporal patterns
      of malaria in Bangladesh.

PMID- 22607349
TI  - Left ventricular diastolic dysfunction in newly diagnosed untreated hypertensive
      patients.
AB  - Essential hypertension is characterized by a left ventricular dysfunction.
      However, the majority of the studies performed so far investigated patients under
      drug treatment and/or with concomitant diseases, such as obesity, diabetes,
      metabolic syndrome or coronary heart disease, which per se may affect diastolic
      function independently on the blood pressure elevation. The present study aimed
      at investigating left ventricular diastolic function in untreated, uncomplicated
      and newly diagnosed hypertensive patients by employing both routine echo-Doppler
      and pulse tissue-Doppler technique. Data were collected in 86 middle-aged
      essential hypertensive patients and in 18 sex-matched normotensive controls. At
      the echo-Doppler approach, about half of the hypertensive patients displayed a
      diastolic dysfunction (n = 44, E/A: 0.79 +/- 0.02). They showed body mass index
      values slightly greater than hypertensive patients without diastolic dysfunction
      but superimposable blood pressure values and metabolic variables. When assessed
      via the pulse tissue-Doppler approach, patients with a reduced E/A displayed an
      Em/Am ratio significantly lower than patients without diastolic dysfunction and
      control subjects. This was the case when the data were related to the lateral and
      septal mitral annulus or averaged together. Furthermore, whereas myocardial
      systolic peak velocity (Sm) was lower in hypertensive patients than in control
      subjects, no significant between-groups difference in E/Em ratio was observed.
      Differently from the data obtained via the echo-Doppler approach, the tissue
      Doppler method in patients without diastolic dysfunction showed a significant
      higher deceleration and isovolumetric relaxation times, with a lower Em velocity
      compared with the normotensive subjects. At the stepwise multiple regression
      analysis E/A ratio and E'/A' values were related with left ventricular mass index
      and body mass index after correction for age. These data provide evidence that
      diastolic dysfunction is of frequent detection in the earlier uncomplicated
      phases of the disease and that tissue Doppler detects an initial impairment of
      left ventricular relaxation in the patients in which at echo Doppler is still
      normal.

PMID- 22607350
TI  - Four novel mutations of the ATP2C1 gene in Chinese patients are associated with
      familial benign chronic pemphigus.

PMID- 22607352
TI  - Standardization and utilization of biobank resources in clinical protein science
      with examples of emerging applications.
AB  - Biobanks are a major resource to access and measure biological constituents that
      can be used to monitor the status of health and disease, both in unique
      individual samples and within populations. Most "omic" activities rely on access
      to these collections of stored samples to provide the basis for establishing the
      ranges and frequencies of expression. Furthermore, information about the relative
      abundance and form of protein constituents found in stored samples provides an
      important historical index for comparative studies of inherited, epidemic, and
      developing disease. Standardizations of sample quality, form, and analysis are an
      important unmet need and requirement for gaining the full benefit from collected
      samples. Coupled to this standard is the provision of annotation describing
      clinical status and metadata of measurements of clinical phenotype that
      characterizes the sample. Today we have not yet achieved consensus on how to
      collect, manage, and build biobank archives in order to reach goals where these
      efforts are translated into value for the patient. Several initiatives (OBBR,
      ISBER, BBMRI) that disseminate best practice examples for biobanking are expected
      to play an important role in ensuring the need to preserve the sample integrity
      of biosamples stored for periods that reach one or several decades. These
      developments will be of great value and importance to programs such as the
      Chromosome Human Protein Project (C-HPP) that will associate protein expression
      in healthy and disease states with genetic foci along of each of the human
      chromosomes.

PMID- 22607351
TI  - Optimization of single shot 3D breath-hold non-enhanced MR angiography of the
      renal arteries.
AB  - BACKGROUND: Cardiac and navigator-gated, inversion-prepared non-enhanced magnetic
      resonance angiography techniques can accurately depict the renal arteries without
      the need for contrast administration. However, the scan time and effectiveness of
      navigator-gated techniques depend on the subject respiratory pattern, which at
      times results in excessively prolonged scan times or suboptimal image quality. A
      single-shot 3D magnetization-prepared steady-state free precession technique was
      implemented to allow the full extent of the renal arteries to be depicted within
      a single breath-hold. METHODS: Technical optimization of the breath-hold
      technique was performed with fourteen healthy volunteers. An alternative
      magnetization preparation scheme was tested to maximize inflow signal.
      Quantitative and qualitative comparisons were made between the breath-hold
      technique and the clinically accepted navigator-gated technique in both
      volunteers and patients on a 1.5 T scanner. RESULTS: The breath-hold technique
      provided an average of seven fold reduction in imaging time, without significant
      loss of image quality. Comparable single-to-noise and contrast-to-noise ratios of
      intra- and extra-renal arteries were found between the breath-hold and the
      navigator-gated techniques in volunteers. Furthermore, the breath-hold technique
      demonstrated good image quality for diagnostic purposes in a small number of
      patients in a pilot study. CONCLUSIONS: The single-shot, breath-hold technique
      offers an alternative to navigator-gated methods for non-enhanced renal magnetic
      resonance angiography. The initial results suggest a potential supplementary
      clinical role for the breath-hold technique in the evaluation of suspected renal
      artery diseases.

PMID- 22607353
TI  - Automated measurement of nitrogen trifluoride in ambient air.
AB  - We present an analytical method for the in situ measurement of atmospheric
      nitrogen trifluoride (NF(3)), an anthropogenic gas with a 100-year global warming
      potential of over 16,000. This potent greenhouse gas has a rising atmospheric
      abundance due to its emission from a growing number of manufacturing processes
      and an expanding end-use market. Here we present a modified version of the
      "Medusa" preconcentration gas chromatography/mass spectrometry (GC/MS) system of
      Miller, B. R.; Weiss, R. F.; Salameh, P. K.; Tanhua, T.; Greally, B. R.; Muhle,
      J.; Simmonds, P. G. Anal. Chem.2008, 80 (5), 1536-1545. By altering the
      techniques of gas separation and chromatography after initial preconcentration,
      we are now able to make atmospheric measurements of NF(3) with relative precision
      <2% (1sigma) for current background clean air samples. Importantly, this method
      augments the currently operational Medusa system, so that the quality of data for
      species already being measured is not compromised and NF(3) is measured from the
      same preconcentrated sample. We present the first in situ measurements of NF(3)
      from La Jolla, California made 11 times daily, illustrating how global deployment
      of this technique within the AGAGE (Advanced Global Atmospheric Gases Experiment)
      network could facilitate estimation of global and regional NF(3) emissions over
      the coming years.

PMID- 22607354
TI  - Regulation of the growth of cotton bollworms by metabolites from an
      entomopathogenic fungus Paecilomyces cateniobliquus.
AB  - Chemical investigation of one entomopathogenic fungus Paecilomyces cateniobliquus
      YMF1.01799 led to the isolation and identification of six metabolites, which
      include three new compounds (2-3, and 5) and three known metabolites. Their
      structures were established by spectroscopic studies such as 1D and 2D NMR and MS
      analysis. Insect growth experiments suggested that polyketide-derived compound 1
      showed significant inhibitory effect on the growth of cotton bollworm Helicoverpa
      armigera, while terpenoid-derived metabolite 5 promoted the growth of the larvae.
      The findings revealed that the entomopathogenic fungus P. cateniobliquus could
      produce different types of metabolites to regulate growth of the insect.

PMID- 22607355
TI  - Clinical and polysomnographic determinants of snoring.
AB  - Snoring is considered one of the hallmarks of sleep-disordered breathing, but its
      determinants remain obscure in both obstructive sleep apnoea (apnoeic) and non
      apnoeic snorers. We aimed to document positional dependency of snoring along with
      its association with clinical and polysomnographic variables. Seventy-seven
      apnoeic and 27 non-apnoeic snorers who complained for every-night loud snoring
      and slept in supine and lateral positions in all sleep stages during overnight
      polysomnography were included. Snoring (i.e. sound intensity > 40 dB) was
      quantified by measuring the mean and maximum sound intensity, and snoring
      frequency. In apnoeic and non-apnoeic snorers, mean snoring intensity and snoring
      frequency were higher in supine than in lateral positions irrespective of sleep
      stage, and were also usually higher in N3 in comparison to rapid eye movement
      and/or N2 sleep stage in any given position. Positional change in snoring
      intensity as expressed by the ratio of mean intensity in the supine to lateral
      positions was independently and positively correlated with body mass index,
      tonsils size and age in the total of patients. Snoring is more prominent in the
      supine position and in N3 sleep stage in apnoeic and non-apnoeic snorers. Snoring
      positional dependence is determined by body mass index, tonsils size and age.

PMID- 22607357
TI  - Anti-inflammatory activity of the active components from the roots of Cosmos
      bipinnatus in lipopolysaccharide-stimulated RAW 264.7 macrophages.
AB  - We isolated a sesquiterpene lactone from the methanol extract of the roots of
      Cosmos bipinnatus, namely, MDI (a mixture of dihydrocallitrisin and isohelenin).
      The anti-inflammatory activity of MDI was evaluated using lipopolysaccharide
      (LPS)-stimulated RAW 264.7 macrophages. MDI significantly inhibited the
      expression of inducible nitric oxide synthase and cyclooxygenase-2. Consistent
      with these results, the production of NO and prostaglandin E2 (PGE2) was
      suggested to be suppressed by MDI in a concentration-dependent manner (IC50 value
      was 0.94 and 2.88 ug mL(-1) for NO and PGE2, respectively). In addition, MDI
      significantly inhibited the expressions of pro-inflammatory cytokines such as IL
      1beta, IL-6, IFN-gamma and TNF-alpha. Furthermore, MDI attenuated DNA-binding
      activity of NF-kappaB by inhibiting the phosphorylation of IkappaB. These results
      indicate that MDI isolated from the roots of C. bipinnatus shows anti
      inflammatory activity in LPS-stimulated murine macrophages by modulating the NF
      kappaB pathway.

PMID- 22607356
TI  - Bone resorption markers and dual-energy x-ray absorptiometry in dogs with
      avascular necrosis, degenerative joint disease, and trauma of the coxofemoral
      joint.
AB  - OBJECTIVES: To compare the ability of N-terminal telopeptide (NTx) assays and
      dual-energy x-ray absorptiometry (DEXA) to detect bone resorption in dogs with
      nonneoplastic bone lysis and evaluate the correlation between these diagnostic
      tools. STUDY DESIGN: Prospective, cross-sectional clinical study. ANIMALS: Dogs
      (n = 35; 39 femoral heads) that had femoral head and neck ostectomy and 6 cadaver
      specimens from healthy immature small dogs. METHODS: Small dogs with avascular
      necrosis (n = 12), a reference group of small dogs (7), large dogs with
      degenerative joint disease (DJD; 10), and large dogs with trauma (10) were
      studied in addition to 6 femoral heads harvested from 6 small immature and
      healthy dogs euthanatized for reasons unrelated to this study. Densitometric
      measurements of femoral heads, urine NTx excretion, and serum NTx concentration
      were compared between groups. RESULTS: Avascular necrosis resulted in a decrease
      in bone mineral density (BMD) (0.18 +/- 0.01 g/cm(2;) P < .01) of the femoral
      head and elevation of serum NTx (159.3 +/- 59.4 nM; P = .03) compared to small
      dog controls (0.28 +/- 0.02 g/cm(2) ; 18.7 +/- 1.83 nM, respectively), but did
      not seem to affect urine NTx. DJD in large dogs did not seem to affect any of the
      densitometric parameters evaluated. BMD (P = .03) and serum NTx (P = .04) were
      lower in small compared to large dogs. Serum NTx and densitometric measurements
      correlate inversely with each other (P = .001) but neither test correlated with
      urine NTx (P = .8-.9). CONCLUSION: Serum NTx levels vary with dog size but seem
      to correlate better with BMD better than urine NTx excretion in dogs with
      nonneoplastic bone resorption.

PMID- 22607361
TI  - Aneuploidy detection in paraffin embedded tissue from products of conception by
      mini-STR genotyping.
AB  - Autosomal trisomy is the most common genetic abnormality observed in pregnancy
      loss. We designed a panel of mini-short tandem repeats (mini-STRs) for aneuploidy
      detection in chromosomes 13, 16, 18 and 21 from fresh and formalin fixed,
      paraffin embedded (FFPE) samples from products of conception (POC). FFPE POCs
      with trisomy 13 (n = 6), trisomy 18 (n = 6), trisomy 21 (n = 12), 6 euploid for
      the chromosomes of interest and two trisomy 16 samples from fresh tissue were
      tested. Concordance between cytogenetics and genotyping was 100% for non-mosaic
      samples. Mini-STR genotyping is a viable method for targeted aneuploidy detection
      in low quality DNA samples.

PMID- 22607362
TI  - Interaction of liposomal formulations of meta-tetra(hydroxyphenyl)chlorin
      (temoporfin) with serum proteins: protein binding and liposome destruction.
AB  - mTHPC is a non polar photosensitizer used in photodynamic therapy. To improve its
      solubility and pharmacokinetic properties, liposomes were proposed as drug
      carriers. Binding of liposomal mTHPC to serum proteins and stability of drug
      carriers in serum are of major importance for PDT efficacy; however, neither was
      reported before. We studied drug binding to human serum proteins using size
      exclusion chromatography. Liposomes destruction in human serum was measured by
      nanoparticle tracking analysis (NTA). Inclusion of mTHPC into conventional
      (Foslip((r))) and PEGylated (Fospeg((r))) liposomes does not affect equilibrium
      serum protein binding compared with solvent-based mTHPC. At short incubation
      times the redistribution of mTHPC from Foslip((r)) and Fospeg((r)) proceeds by
      both drug release and liposomes destruction. At longer incubation times, the drug
      redistributes only by release. The release of mTHPC from PEGylated vesicles is
      delayed compared with conventional liposomes, alongside with greatly decreased
      liposomes destruction. Thus, for long-circulation times the pharmacokinetic
      behavior of Fospeg((r)) could be influenced by a combination of protein- and
      liposome-bound drug. The study highlights the modes of interaction of
      photosensitizer-loaded nanovesicles in serum to predict optimal drug delivery and
      behavior in vivo in preclinical models, as well as the novel application of NTA
      to assess the destruction of liposomes.

PMID- 22607363
TI  - Quantitative light fluorescence (QLF) and polarized white light (PWL) assessments
      of dental fluorosis in an epidemiological setting.
AB  - BACKGROUND: To determine if a novel dual camera imaging system employing both
      polarized white light (PWL) and quantitative light induced fluorescence imaging
      (QLF) is appropriate for measuring enamel fluorosis in an epidemiological
      setting. The use of remote and objective scoring systems is of importance in
      fluorosis assessments due to the potential risk of examiner bias using clinical
      methods. METHODS: Subjects were recruited from a panel previously characterized
      for fluorosis and caries to ensure a range of fluorosis presentation. A total of
      164 children, aged 11 years (+/-1.3) participated following consent. Each child
      was examined using the novel imaging system, a traditional digital SLR camera,
      and clinically using the Dean's and Thylstrup and Fejerskov (TF) Indices on the
      upper central and lateral incisors. Polarized white light and SLR images were
      scored for both Dean's and TF indices by raters and fluorescence images were
      automatically scored using software. RESULTS: Data from 164 children were
      available with a good distribution of fluorosis severity. The automated software
      analysis of QLF images demonstrated significant correlations with the clinical
      examinations for both Dean's and TF index. Agreement (measured by weighted
      Kappa's) between examiners scoring clinically, from polarized photographs and
      from SLR images ranged from 0.56 to 0.92. CONCLUSIONS: The study suggests that
      the use of a digital imaging system to capture images for either automated
      software analysis, or remote assessment by raters is suitable for epidemiological
      work. The use of recorded images enables study archiving, assessment by multiple
      examiners, remote assessment and objectivity due to the blinding of subject
      status.

PMID- 22607364
TI  - iHAT: interactive hierarchical aggregation table for genetic association data.
AB  - In the search for single-nucleotide polymorphisms which influence the observable
      phenotype, genome wide association studies have become an important technique for
      the identification of associations between genotype and phenotype of a diverse
      set of sequence-based data. We present a methodology for the visual assessment of
      single-nucleotide polymorphisms using interactive hierarchical aggregation
      techniques combined with methods known from traditional sequence browsers and
      cluster heatmaps. Our tool, the interactive Hierarchical Aggregation Table
      (iHAT), facilitates the visualization of multiple sequence alignments, associated
      metadata, and hierarchical clusterings. Different color maps and aggregation
      strategies as well as filtering options support the user in finding correlations
      between sequences and metadata. Similar to other visualizations such as parallel
      coordinates or heatmaps, iHAT relies on the human pattern-recognition ability for
      spotting patterns that might indicate correlation or anticorrelation. We
      demonstrate iHAT using artificial and real-world datasets for DNA and protein
      association studies as well as expression Quantitative Trait Locus data.

PMID- 22607365
TI  - Factors associated with missing teeth in the Brazilian elderly institutionalised
      population.
AB  - OBJECTIVE: Identify factors associated with missing teeth in the elderly
      institutionalised population in Brazil. METHODOLOGY: Cross-sectional study of
      elderly institutionalised Brazilians with 1192 subjects. A questionnaire was
      applied as well as an epidemiological survey of oral health conditions in
      accordance with WHO. Factorial analysis was carried out with variables related to
      missing teeth, as well as the Fisher's exact test, chi-squared test and multiple
      logistic regression. RESULTS: Mean age was 76.3 (+/- 9.8), 53.5% (638) of
      subjects were women and 717 (60.2) were dependent. Mean of Decayed Missing and
      Filled Teeth Index (DMFT index) was 29.4 (+/- 4.9). The subjects that did not use
      upper and lower dentures were 61.5% (732) and 79.2% (944), respectively. Median
      number of missing teeth per person was 27.88 (+/- 6.8) with a mean of 4 (+/- 6.6)
      teeth present and 2.4 (+/- 4.5) caries-free teeth. Factors associated with
      missing teeth following multivariate analysis were: age, sex, self-assessment of
      oral health, access to health services, type of institution and area of the
      country. CONCLUSIONS: High level of tooth loss and low level of rehabilitation
      demonstrate precarious oral health. It is therefore necessary to improve
      institutional access mechanisms to public health facilities for the
      institutionalised elderly.

PMID- 22607366
TI  - Rare or orphan diseases -- a useful political concept.

PMID- 22607368
TI  - Resveratrol induces apoptosis associated with mitochondrial dysfunction in
      bladder carcinoma cells.
AB  - OBJECTIVE: Resveratrol shows chemopreventive activity in a variety of human
      cancers by targeting mitochondria and triggering apoptosis. The purpose of this
      study was to investigate the antitumor action of resveratrol in bladder cancer
      and its underlying mechanism. METHODS: Using two different bladder cell lines,
      BTT739 and T24, the cytotoxicity of resveratrol were determined by MTT assay. The
      apoptosis induced by resveratrol was assayed by transferase dUTP nick end
      labeling staining. To show whether the mitochondrial dysfunction involved in the
      effects of resveratrol, mitochondrial function was detected by mitochondrial
      membrane potential, reactive oxygen species production and adenosine 5'
      triphosphate content. In addition, the markers of apoptosis in the intrinsic
      mitochondrial-dependent pathway were analyzed by the release of cytochrome c and
      the activities of caspase-9 and caspase-3. RESULTS: Resveratrol effectively
      decreased cell viability and induced apoptosis in a concentration- and time
      dependent manner. In addition, resveratrol significantly disrupted the
      mitochondrial membrane potential in both intact cells and isolated mitochondria.
      Resveratrol also increased reactive oxygen species production and reduced
      adenosine 5'-triphosphate concentrations. Western blot analysis showed that
      resveratrol provoked the release of cytochrome c from mitochondria to the
      cytosol. Furthermore, resveratrol significantly promoted the activation of
      caspase-9 and caspase-3. CONCLUSIONS: These findings suggest that resveratrol
      efficiently triggers apoptosis in bladder cancer cells through the intrinsic
      mitochondrial-dependent pathway, which is associated with mitochondrial
      dysfunction. Resveratrol might have great pharmacological promise in the
      treatment of bladder cancer.

PMID- 22607367
TI  - Survivin regulates the expression of VEGF-C in lymphatic metastasis of breast
      cancer.
AB  - BACKGROUND: As a known regulator of apoptosis, survivin has positive relationship
      with lymphatic metastasis in breast cancer. This study aims to detect the
      difference in expression between survivin and vascular endothelial growth factor
      C (VEGF-C) in treated breast cancer cells and tissues, and to analyze the
      correlation among survivin, VEGF-C and lymphatic metastasis. METHODS: Plasmid
      with survivin and VEGF-C shRNA and lentivirus with survivin gene were constructed
      and transfected into breast cancer cell ZR-75-30. Then the expressions of the two
      genes were examined using western blot analysis and real-time PCR. The change of
      invasiveness of breast cancer cells was assessed using matrigel invasion assay.
      Using immunohistochemistry, the expression of survivin and VEGF-C were analyzed
      in 108 clinical breast cancer cases with breast cancer tissue and lymph node.
      RESULTS: Survivin regulated the expression of VEGF-C at both protein and mRNA
      levels in breast cancer cells. Immunohistochemical analysis showed that the level
      of VEGF-C expression was significantly related with that of survivin in breast
      cancer tissues (p<0.05). VEGF-C was found to participate in the process of breast
      cancer cells invasion mediated by survivin. The co-expression of the two and the
      single expression of any one took significant difference in positive lymph node
      (p<0.05). CONCLUSIONS: Survivin takes an important part in regulating the
      expression of VEGF-C. VEGF-C could influence the invasive ability mediated by
      survivin. The co-expression of survivin and VEGF-C is more statistically
      significant to assess lymphatic metastasis in breast cancer. VIRTUAL SLIDES: The
      virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/9193530897100952.

PMID- 22607369
TI  - Hemodynamic contribution of stem cell scaffolding in acute injured myocardium.
AB  - Tissue-engineered scaffolds may improve experimental outcomes in cardiac cell
      therapy by targeted delivery of stem cells and mechanically support an infarcted
      left ventricular (LV) wall. We transplanted cardiomyocyte-like cells (5*10(5))
      with scaffolding via epicardial patching (cell patch, n=17) or a low-dose
      intramyocardial hydrogel (LD hydrogel, n=18), a high-dose (5*10(6))
      intramyocardial hydrogel (HD hydrogel, n=18) or transplanting a serum-free medium
      control (control, n=13), a blank patch (n=14), and a blank gel (n=16) for
      targeted cardiomyoplasty in a myocardial infarcted rat model. LV real-time
      hemodynamics were assessed using a 1.9-F pressure-volume catheter 7 weeks after
      stem cell transplantation. All mode of scaffold transplantation protected
      diastolic function by preserving LV wall integrity that resulted in a lower end
      diastolic pressure-volume relationship (EDPVR) as compared to a control medium
      injected group. Moreover, epicardial patching, but not hydrogel injection,
      reduced ventricular wall stress with a significantly better LV end diastolic
      pressure (EDP: 5.3+/-2.4 mmHg vs. 9.6+/-6.9 mmHg, p<0.05) as compared to control.
      Furthermore, epicardial patching additionally preserved systolic function by
      modulating negative remodeling through restricting dilatation of the LV chamber.
      In comparison to control, an improved ejection fraction in the cell patch group
      (80.1%+/-5.9% vs. 67.9%+/-3.2%, p<0.01) was corroborated by load-independent
      enhancement of the end systolic pressure-volume relationship (ESPVR: 0.88+/-0.61
      mmHg/uL vs. 0.29+/-0.19 mmHg/uL, p<0.05) and preload recruitable stroke work
      (PRSW: 68.7+/-26.4 mmHg vs. 15.6+/-16.2 mmHg, p<0.05) in systolic function.
      Moreover, the cell patch group (14.2+/-1.7 cells/high-power field vs. 7.4+/-1.6
      cells/high power field, p<0.05) was significantly better in myocardial retention
      of transplanted stem cells as compared to the LD hydrogel group. Collectively,
      myocardial transplantation of compliant scaffolding materials alone may
      physically improve wall mechanics, largely independent of stem cells. However,
      epicardially grafted cell patch conferred added systolic contractility by
      improving stem cell retention and cellular alignment leading to improved LV
      remodeling and geometric preservation postinfarction.

PMID- 22607370
TI  - Diagnosis of and treatment for symptomatic carotid stenosis: an updated review.
AB  - Carotid stenoses of >=50% account for about 15-20% of strokes. Their degree may
      be moderate (50-69%) or severe (70-99%). Current diagnostic methods include
      ultrasound, MR- or CT-angiography. Stenosis severity, irregular plaque surface,
      and presence of microembolic signals detected by transcranial Doppler predict the
      early recurrence risk, which may be as high as 20%. Initial therapy comprises
      antiplatelets and statins. Benefit of revascularization is greater in men, in
      older patients, and in severe stenosis; patients with moderate stenoses may also
      profit particularly if the plaque has an irregular aspect. An intervention should
      be performed within <2 weeks. In large randomized studies comparing
      endarterectomy and stenting, endovascular therapy was associated with a higher
      risk of periprocedural stroke, yet in some studies, with a lower risk of
      myocardial infarction and of cranial neuropathy. These trials support
      endarterectomy as the first choice treatment. Risk factors for each of the two
      therapies have been indentified: coronary artery disease, neck radiation,
      contralateral laryngeal nerve palsy for endarterectomy, and, elderly patients
      (>70 years), arch vessel tortuosity and plaques with low echogenicity on
      ultrasound for carotid stenting. Lastly, in direct comparisons, a contralateral
      occlusion increases the risk of periprocedural complications in both types of
      treatment.

PMID- 22607371
TI  - Na+, Ca2+, and Mg2+ in brines affect supercritical CO2-brine-biotite
      interactions: ion exchange, biotite dissolution, and illite precipitation.
AB  - For sustainable geologic CO(2) sequestration (GCS), a better understanding of the
      effects of brine cation compositions on mica dissolution, surface morphological
      change, and secondary mineral precipitation under saline hydrothermal conditions
      is needed. Batch dissolution experiments were conducted with biotite under
      conditions relevant to GCS sites (55-95  degrees C and 102 atm CO(2)). One molar
      NaCl, 0.4 M MgCl(2), or 0.4 M CaCl(2) solutions were used to mimic different
      brine compositions, and deionized water was used for comparison. Faster ion
      exchange reactions (Na(+)-K(+), Mg(2+)-K(+), and Ca(2+)-K(+)) occurred in these
      salt solutions than in water (H(+)-K(+)). The ion exchange reactions affected
      bump, bulge, and crack formation on the biotite basal plane, as well as the
      release of biotite framework ions. In these salt solutions, numerous illite
      fibers precipitated after reaction for only 3 h at 95  degrees C. Interestingly,
      in slow illite precipitation processes, oriented aggregation of hexagonal
      nanoparticles forming the fibrous illite was observed. These results provide new
      information for understanding scCO(2)-brine-mica interactions in saline aquifers
      with different brine cation compositions, which can be useful for GCS as well as
      other subsurface projects.

PMID- 22607372
TI  - Solvothermal synthesis of zincblende and wurtzite CuInS2 nanocrystals and their
      photovoltaic application.
AB  - We report a simple solvothermal synthesis approach to the growth of CuInS(2)
      nanocrystals with zincblende- and wurtzite-phase structures. Zincblende
      nanocrystals with particle sizes of 10-20 nm were produced using oleylamine as
      the solvent. When ethylenediamine was used as the solvent, similarly sized
      wurtzite nanocrystals with some degree of particle aggregation were formed. Use
      of a mixture of these solvents gave products with mixed phases including some
      polyhedral nanostructures. The crystal phases of these nanocrystals were
      carefully determined by X-ray diffraction and transmission electron microscopy
      analysis. All the samples exhibit strong absorption from the entire visible light
      region to the near-infrared region beyond 1300 nm. Pure-phase zincblende and
      wurtzite CuInS(2) nanocrystals were employed as ink in the fabrication of solar
      cells. The spray-coated nanocrystal layer was subjected to a selenization
      process. A power conversion efficiency of ~0.74% and a good external quantum
      efficiency profile over broad wavelengths have been measured. The results
      demonstrate that wurtzite and zincblende CuInS(2) nanocrystals may be attractive
      precursors to light-absorbing materials for making efficient photovoltaic
      devices.

PMID- 22607373
TI  - Antioxidant and repellent activities of the essential oil from Colombian
      Triphasia trifolia (Burm. f.) P. Wilson.
AB  - The chemical composition of essential oils isolated from aerial parts of
      Triphasia trifolia (Burm. f.) P. Wilson was analyzed using hydrodistillation by
      GC-MS. The main constituents found were beta-pinene (64.36%), (+)-sabinene
      (8.75%), hexadecanoic acid (6.03%), alpha-limonene (4.24%) and p-cymene (2.73%).
      The essential oil from T. trifolia shows high antioxidant potential (94.53%), an
      effect that is comparable with ascorbic acid (96.40%), used as standard. In
      addition, these oils had high repellent effects on the insect Tribolium castaneum
      Herbst (99% +/- 1) at 0.2 MUL/cm(2) after 2 h of exposure.

PMID- 22607374
TI  - Decisional procalcitonin thresholds are not adapted to elderly patients admitted
      to the emergency room.
AB  - CONTEXT: Diagnosis of sepsis in elderly is challenging. OBJECTIVES: We
      investigated whether procalcitonin concentrations in elderly differed from values
      for the general population. METHODS: Procalcitonin measurement was assessed
      prospectively in 307 apyretic patients >=75 years visiting the emergency
      department. RESULTS: Median age was 86 years [IQR81-90] and 222 (72%) were
      female. Procalcitonin concentration was 0.057 ug/L [0.040-0.092]; 99th percentile
      was 0.661 ug/L. Patients with procalcitonin concentrations above decisional
      thresholds had lower glomerular filtration rate and higher C-reactive protein
      concentrations. CONCLUSIONS: Baseline procalcitonin levels are increased in
      elderly. Elevated values are common and associated to low-grade inflammation and
      lower eGFR.

PMID- 22607375
TI  - Increasing levels of wild-type CREB up-regulates several activity-regulated
      inhibitor of death (AID) genes and promotes neuronal survival.
AB  - BACKGROUND: CREB (cAMP-response element binding protein) is the prototypical
      signal-regulated transcription factor. In neurons, it is the target of the
      synaptic activity-induced nuclear calcium-calcium/calmodulin dependent protein
      kinase (CaMK) IV signaling pathway that controls the expression of genes
      important for acquired neuroprotection as well as other long-lasting adaptive
      processes in the nervous system. The function of CREB as a transcriptional
      activator is controlled by its phosphorylation on serine 133, which can be
      catalyzed by CaMKIV and leads to the recruitment of the co-activator, CREB
      binding protein (CBP). Activation of CBP function by nuclear calcium-CaMKIV
      signaling is a second regulatory step required for CREB/CBP-mediated
      transcription. RESULTS: Here we used recombinant adeno-associated virus (rAAV) to
      increase the levels of wild type CREB or to overexpress a mutant version of CREB
      (mCREB) containing a serine to alanine mutation at position amino acid 133 in
      mouse hippocampal neurons. Increasing the levels of CREB was sufficient to boost
      neuroprotective activity even under basal conditions (i.e., in the absence of
      stimulation of synaptic activity). In contrast, overexpression of mCREB increased
      cell death. The ratio of phospho(serine 133)CREB to CREB immunoreactivity in
      unstimulated hippocampal neurons was similar for endogenous CREB and
      overexpressed wild type CREB and, as expected, dramatically reduced for
      overexpressed mCREB. A gene expression analysis revealed that increased
      expression of CREB but not that of mCREB in hippocampal neurons led to elevated
      expression levels of bdnf as well as that of several members of a previously
      characterized set of Activity-regulated Inhibitor of Death (AID) genes, which
      include atf3, btg2, gadd45beta, and gadd45gamma. CONCLUSIONS: Our findings
      indicate that the expression levels of wild type CREB are a critical determinant
      of the ability of hippocampal neurons to survive harmful conditions. Increasing
      the levels of wild type CREB can, even without inducing synaptic activity,
      increase pro-survival gene expression and strengthen the neurons' neuroprotective
      shield. The observed degradation of CREB protein following NMDA treatment of
      hippocampal neurons suggests that the known CREB shut-off associated with
      extrasynaptic NMDA receptor-induced excitotoxicity is followed by CREB
      proteolysis.

PMID- 22607376
TI  - Minimizing risk of nephrogenic systemic fibrosis in cardiovascular magnetic
      resonance.
AB  - Nephrogenic Systemic Fibrosis is a rare condition appearing only in patients with
      severe renal impairment or failure and presents with dermal lesions and
      involvement of internal organs. Although many cases are mild, an estimated 5%
      have a progressive debilitating course. To date, there is no known effective
      treatment thus stressing the necessity of ample prevention measures. An
      association with the use of Gadolinium based contrast agents (GBCA) makes
      Nephrogenic Systemic Fibrosis a potential side effect of contrast enhanced
      magnetic resonance imaging and offers the opportunity for prevention by limiting
      use of gadolinium based contrast agents in renal failure patients. In itself
      toxic, Gadolinium is embedded into chelates that allow its safe use as a contrast
      agent. One NSF theory is that Gadolinium chelates distribute into the
      extracellular fluid compartment and set Gadolinium ions free, depending on
      multiple factors among which the duration of chelates exposure is directly
      related to the renal function. Major medical societies both in Europe and in
      North America have developed guidelines for the usage of GBCA. Since the
      establishment of these guidelines and the increased general awareness of this
      condition, the occurrence of NSF has been nearly eliminated. Giving an overview
      over the current knowledge of NSF pathobiochemistry, pathogenesis and treatment
      options this review focuses on the guidelines of the European Medicines Agency,
      the European Society of Urogenital Radiology, the FDA and the American College of
      Radiology from 2008 up to 2011 and the transfer of this knowledge into every day
      practice.

PMID- 22607377
TI  - Persistent hypereosinophilia with Wells syndrome.
AB  - Since Wells and Smith first described cases of eosinophilic cellulitis (Wells
      syndrome; WS) in 1979, it has been noted that some but not all patients with WS
      present with eosinophilia. In the face of idiopathic persistent eosinophilia
      patients will also then fall within the hypereosinophilic syndrome (HES), which
      represents a multifarious spectrum of disorders of varying severity, causes and
      outcomes. In this article we propose that patients who present within the HES
      spectrum with cutaneous findings of WS and with no extracutaneous disease be
      classified as having 'persistent hypereosinophilia with Wells syndrome' (PHEWS).

PMID- 22607379
TI  - The relationship between emotion awareness and somatic complaints in children and
      adolescents: Investigating the mediating role of anxiety and depression.
AB  - The objective of this study was to examine if emotion awareness in children and
      adolescents (age 7-18 years old) is directly related to somatic complaints, and
      if this relationship holds when considering symptoms of anxiety and depression as
      mediating factors. A number of questionnaires measuring emotion awareness,
      symptoms of anxiety and depression and somatic complaints were administered to
      Dutch schoolchildren (N = 617). A path model was constructed, with the use of
      structural equation modelling. The results showed that two aspects of emotion
      awareness (bodily awareness and differentiating between emotions) contributed to
      the prediction of somatic complaints. However, this was no longer the case when
      controlling for symptoms of anxiety and depression. Thus, in this study, no
      direct relation was found between emotion awareness and somatic complaints.
      Instead, the relation was perfectly mediated by symptoms of anxiety and
      depression. The results suggest that focusing only on the relation between
      emotion awareness and somatic complaints is an oversimplified perspective that
      falls short as a starting point to find therapeutic solutions for children who
      suffer from somatic complaints.

PMID- 22607380
TI  - Investigations concerning the application of the cross-correlation method in
      cardiac output measurements.
AB  - BACKGROUND: In spite of numerous non-invasive examinations the "gold clinical
      standard" of cardiac output measurements is the invasive pulmonary artery
      catheterization by means of the Swan-Ganz catheter and the application of the
      thermodilution method to estimate the blood flow. The results obtained by means
      of thermodilution are sensitive to many physical and biological disturbances. The
      unreliability of this method amounts to 20-45% and depends on the given variant
      of the method. Therefore some other method, more accurate and resistant to
      disturbances, was looked for. This paper presents a new approach to cardiac
      output measurements, based on cross-correlation signal analysis. The goal of
      investigations was to verify experimentally the application of the cross
      correlation method of cardiac output measurements. RESULTS: In 99.2% of the
      examined cases the extreme of the cross-correlation function was easy to be
      estimated by numerical algorithms. In 0,8% of the remaining cases (with a plateau
      region adjacent to the maximum point) numerical detection of the extreme was
      inaccurate. The typical unreliability of the investigated method amounted o 5.1%
      (9.8% in the worst case). Investigations performed on a physical model revealed
      that the unreliability of cardiac output measurements by means of the cross
      correlation method is 3-5 times better than in the case of thermodilution.
      CONCLUSIONS: The performed investigations and theoretical analysis have shown,
      that the cross-correlation method may be applied in cardiac output measurements.
      This kind of measurements seems to be more accurate and disturbance-resistant
      than clinically applied thermodilution.

PMID- 22607381
TI  - Engineering nitrogen use efficient crop plants: the current status.
AB  - In the last 40 years the amount of synthetic nitrogen (N) applied to crops has
      risen drastically, resulting in significant increases in yield but with
      considerable impacts on the environment. A requirement for crops that require
      decreased N fertilizer levels has been recognized in the call for a 'Second Green
      Revolution' and research in the field of nitrogen use efficiency (NUE) has
      continued to grow. This has prompted a search to identify genes that improve the
      NUE of crop plants, with candidate NUE genes existing in pathways relating to N
      uptake, assimilation, amino acid biosynthesis, C/N storage and metabolism,
      signalling and regulation of N metabolism and translocation, remobilization and
      senescence. Herein is a review of the approaches taken to determine possible NUE
      candidate genes, an overview of experimental study of these genes as effectors of
      NUE in both cereal and non-cereal plants and the processes of commercialization
      of enhanced NUE crop plants. Patents issued regarding increased NUE in plants as
      well as gene pyramiding studies are also discussed as well as future directions
      of NUE research.

PMID- 22607382
TI  - RuleBender: integrated modeling, simulation and visualization for rule-based
      intracellular biochemistry.
AB  - BACKGROUND: Rule-based modeling (RBM) is a powerful and increasingly popular
      approach to modeling cell signaling networks. However, novel visual tools are
      needed in order to make RBM accessible to a broad range of users, to make
      specification of models less error prone, and to improve workflows. RESULTS: We
      introduce RuleBender, a novel visualization system for the integrated
      visualization, modeling and simulation of rule-based intracellular biochemistry.
      We present the user requirements, visual paradigms, algorithms and design
      decisions behind RuleBender, with emphasis on visual global/local model
      exploration and integrated execution of simulations. The support of RBM creation,
      debugging, and interactive visualization expedites the RBM learning process and
      reduces model construction time; while built-in model simulation and results with
      multiple linked views streamline the execution and analysis of newly created
      models and generated networks. CONCLUSION: RuleBender has been adopted as both an
      educational and a research tool and is available as a free open source tool at
      http://www.rulebender.org. A development cycle that includes close interaction
      with expert users allows RuleBender to better serve the needs of the systems
      biology community.

PMID- 22607384
TI  - Preclinical development of TLR ligands as drugs for the treatment of chronic
      viral infections.
AB  - INTRODUCTION: Toll-like receptors (TLRs) have been identified as key regulators
      of innate and adaptive immune responses in viral infection. Recent progress in
      this field revealed that there are significant interactions between the TLR
      system and pathogens in chronic viral infections. Therefore, TLR ligands have
      great potential for the treatment of chronic viral infections. AREAS COVERED:
      This review provides an overview of the methodology for preclinical testing of
      TLR ligands for three major viral infections: hepatitis B virus (HBV), hepatitis
      C virus (HCV) and human immunodeficiency virus (HIV). TLR ligands have shown
      potent antiviral activity in different cell culture systems as well as animal
      models for these infections and induce the production of antiviral cytokines,
      modulated cellular immunological functions and antiviral effects in vivo. EXPERT
      OPINION: The recent progress in this field demonstrated that activation of a
      large number of TLR ligands is effective against viral infections in cell culture
      systems and animal models. Exploring these models, further in-depth elucidation
      of the molecular and immunological mechanisms of the antiviral activity of TLR
      ligands will be necessary to develop them into clinical useful drugs.

PMID- 22607385
TI  - Photosynthetic downregulation in leaves of the Japanese white birch grown under
      elevated CO(2)  concentration does not change their temperature-dependent
      susceptibility to photoinhibition.
AB  - To determine the effects of elevated CO(2) concentration ([CO(2)]) on the
      temperature-dependent photosynthetic properties, we measured gas exchange and
      chlorophyll fluorescence at various leaf temperatures (15, 20, 25, 30, 35 and 40
      degrees C) in 1-year-old seedlings of the Japanese white birch (Betula
      platyphylla var. japonica), grown in a phytotron under natural daylight at two
      [CO(2)] levels (ambient: 400 umol mol(-1) and elevated: 800 umol mol(-1)) and
      limited N availability (90 mg N plant(-1)). Plants grown under elevated [CO(2)]
      exhibited photosynthetic downregulation, indicated by a decrease in the
      carboxylation capacity of Rubisco. At temperatures above 30 degrees C, the net
      photosynthetic rates of elevated-CO(2)-grown plants exceeded those grown under
      ambient [CO(2)] when compared at their growth [CO(2)]. Electron transport rates
      were significantly lower in elevated-CO(2)-grown plants than ambient-CO(2)-grown
      ones at temperatures below 25 degrees C. However, no significant difference was
      observed in the fraction of excess light energy [(1 - q(P))* F(v)'/F(m)'] between
      CO(2) treatments across the temperature range. The quantum yield of regulated non
      photochemical energy loss was significantly higher in elevated-CO(2)-grown plants
      than ambient, when compared at their respective growth [CO(2)] below 25 degrees
      C. These results suggest that elevated-CO(2)-induced downregulation might not
      exacerbate the temperature-dependent susceptibility to photoinhibition, because
      reduced energy consumption by electron transport was compensated for by increased
      thermal energy dissipation at low temperatures.

PMID- 22607386
TI  - Mental health care for irregular migrants in Europe: barriers and how they are
      overcome.
AB  - BACKGROUND: Irregular migrants (IMs) are exposed to a wide range of risk factors
      for developing mental health problems. However, little is known about whether and
      how they receive mental health care across European countries. The aims of this
      study were (1) to identify barriers to mental health care for IMs, and (2) to
      explore ways by which these barriers are overcome in practice. METHODS: Data from
      semi-structured interviews with 25 experts in the field of mental health care for
      IMs in the capital cities of 14 European countries were analysed using thematic
      analysis. RESULTS: Experts reported a range of barriers to mental health care for
      IMs. These include the absence of legal entitlements to health care in some
      countries or a lack of awareness of such entitlements, administrative obstacles,
      a shortage of culturally sensitive care, the complexity of the social needs of
      IMs, and their fear of being reported and deported. These barriers can be partly
      overcome by networks of committed professionals and supportive services. NGOs
      have become important initial points of contact for IMs, providing mental health
      care themselves or referring IMs to other suitable services. However, these
      services are often confronted with the ethical dilemma of either acting according
      to the legislation and institutional rules or providing care for humanitarian
      reasons, which involves the risk of acting illegally and providing care without
      authorisation. CONCLUSIONS: Even in countries where access to health care is
      legally possible for IMs, various other barriers remain. Some of these are common
      to all migrants, whilst others are specific for IMs. Attempts at improving mental
      health care for IMs should consider barriers beyond legal entitlement, including
      communicating information about entitlement to mental health care professionals
      and patients, providing culturally sensitive care and ensuring sufficient
      resources.

PMID- 22607387
TI  - First outbreak of food poisoning caused by Salmonella enterica subspecies
      enterica serovar Berta in Italy.
AB  - AIMS: To provide an epidemiologic interpretation of a suspected outbreak of food
      poisoning caused by Salmonella enterica subspecies enterica serovar Berta strains
      isolated from humans and from the leftovers of the implicated foods (cream, dairy
      based desserts and eggs). METHODS AND RESULTS: We have correlated the similarity
      between the strains through genotyping with Pulsed Field Gel Electrophoresis
      (PFGE), studying antimicrobial sensitivity patterns and epidemiological
      investigation. The clonal origin of the outbreak was confirmed by all laboratory
      tests. PFGE analysis of the restriction profiles obtained with XbaI and SpeI
      revealed a certainly correlation from the strains isolated from the various
      sources, while the antimicrobial sensitivity pattern was the same in all cases,
      with all strains sensitive to all antibiotics tested. CONCLUSIONS: Poor hygiene
      conditions in the facility concerned, lack of hygiene in food handling, high
      summer temperatures and positive cultures from asymptomatic staff could all be
      implicated in the infection, with food being the means through which it spread.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study describes the first outbreak of
      food poisoning caused by Salmonella enterica subspecies enterica serovar Berta
      (Salmonella Berta) reported in Italy. It confirms the importance of correlating
      epidemiological investigations with genotyping and phenotyping to understand the
      dynamics of infection.

PMID- 22607388
TI  - Targeted delivery into motor nerve terminals of inhibitors for SNARE-cleaving
      proteases via liposomes coupled to an atoxic botulinum neurotoxin.
AB  - A targeted drug carrier (TDC) is described for transferring functional proteins
      or peptides into motor nerve terminals, a pivotal locus for therapeutics to treat
      neuromuscular disorders. It exploits the pronounced selectivity of botulinum
      neurotoxin type B (BoNT/B) for interacting with acceptors on these cholinergic
      nerve endings and becoming internalized. The gene encoding an innocuous BoNT/B
      protease-inactive mutant (BoTIM) was fused to that for core streptavidin,
      expressed in Escherichia coli and the purified protein was conjugated to surface
      biotinylated liposomes. Such decorated liposomes, loaded with fluorescein as
      traceable cargo, acquired pronounced specificity for motor nerve terminals in
      isolated mouse hemidiaphragms and facilitated the intraneuronal transfer of the
      fluor, as revealed by confocal microscopy. Delivery of the protease light chain
      of botulinum neurotoxin type A (BoNT/A) via this TDC accelerated the onset of
      neuromuscular paralysis, indicative of improved translocation of this enzyme into
      the presynaptic cytosol with subsequent proteolytic inactivation of synaptosomal
      associated protein of molecular mass 25 kDa (SNAP-25), an exocytotic soluble N
      ethyl-maleimide-sensitive factor attachment protein receptor (SNARE) essential
      for neurotransmitter release. BoTIM-coupled liposomes, loaded with peptide
      inhibitors of proteases, yielded considerable attenuation of the neuroparalytic
      effects of BoNT/A or BoNT/F as a result of their cytosolic transfer, the first in
      situ demonstration of the ability of designer antiproteases to suppress the
      symptoms of botulism ex vivo. Delivery of the BoNT/A inhibitor by liposomes
      targeted with the full-length BoTIM proved more effective than that mediated by
      its C-terminal neuroacceptor-binding domain. This demonstrated versatility of TDC
      for nonviral cargo transfer into cholinergic nerve endings has unveiled its
      potential for direct delivery of functional targets into motor nerve endings.

PMID- 22607389
TI  - Investigation of the frequencies of prenatally diagnosed fetal chromosomal
      abnormalities at a single institution.
AB  - The objective of this study was to investigate, retrospectively, the frequencies
      of fetal chromosomal abnormalities identified in 4176 prenatal cytogenetic
      examinations at the Xiamen Maternity and Child Health Care Hospital over the 5
      year period from October 2005 to September 2010. The frequency of abnormal fetal
      karyotypes was 4.6%. Numerical chromosome abnormalities were identified in 150
      cases. The frequency of trisomy 21 was by far the highest, followed by trisomy
      18. Structural aberrations of chromosomes were identified in 43 cases, including
      21 cases with balanced and 22 cases with unbalanced chromosomal aberrations. In
      addition, 16 cases of apparently de novo chromosomal aberrations and 27 cases of
      familial inheritances were observed. Increased awareness of the frequencies of
      fetal chromosome abnormalities is important for the improvement of prenatal care
      and providing the options of termination or continuation of the pregnancy. Data
      obtained in this study provide the basis of a database for genetic counseling.

PMID- 22607390
TI  - Are we using support workers effectively? the relationship between patient and
      team characteristics and support worker utilisation in older people's community
      based rehabilitation services in England.
AB  - This research explores the relationship between support worker utilisation and
      patient- and team-level characteristics using a prospective longitudinal study of
      20 older people's community rehabilitation teams. Between January and September
      2009, 462 Whole Time Equivalent Staff and 1913 patients participated in the
      study. Patient dependency, health status (Therapy Outcome Measures, EQ-5D and
      Levels of Care tool) and demographic data were collected alongside detailed staff
      activity data for patients during the recruitment period. Multivariate analyses
      were used to determine the relationship between the proportion of care delivered
      by support workers team and patient variables. Support workers delivered up to
      36% of direct patient care and spent less time per patient contact (36.0 minutes,
      SD 37.7, range 0-600) than qualified professionals (mean time per contact 75.8
      minutes, SD 32.9, range 0-334). Less-dependent and female patients had a greater
      proportion of support worker input, with a 4.9% increase in face-to-face support
      worker time for every 0.1 unit increase in EQ-5D (95% CI 0.3-9.6, P = 0.038),
      while females had an additional 5.1% of their total contact time with support
      workers compared with males (95% CI 1.9-8.4, P = 0.002). In an analysis without
      EQ-5D, older patients had a greater proportion of support worker time (P =
      0.006). Other factors associated with support worker input include the referral
      source, intensity of care, usual living arrangements and proportion of support
      staff in a team. Results indicate that patient- and team-level factors are a
      determinant in the proportion of support worker care delivered to older people in
      the community, suggesting that it may be appropriate to introduce a more explicit
      targeted deployment of support workers based on patient-level characteristics,
      which may facilitate a more effective use of qualified practitioner time for more
      complex, dependent patients.

PMID- 22607391
TI  - Effect of hydrostatic pressure on bone regeneration using human mesenchymal stem
      cells.
AB  - BACKGROUND: Mechanics is increasingly being recognized as the fourth essential
      factor in bone tissue engineering next to cell, scaffold, and growth factors. The
      development of bioprocessors has made it possible to simulate the in vivo
      mechanics that are needed to generate three-dimensional (3D) bone constructs.
      However, although hydrostatic pressure (HP) is a dominant and constant mechanical
      strain on bone cells in vivo, little is known about the effect of HP applied via
      perfusion bioprocessors on in vitro human bone marrow-derived mesenchymal stem
      cell (hMSC) behavior. METHODS: hMSCs underwent primary culture for three passages
      before being seeded into hydroxyapatite (HA) scaffolds. The scaffolds were
      incubated for 3 weeks in an automated bioprocessor under cyclic HP. Scaffolds
      exposed to atmospheric pressure (AP) served as the comparator. Osteogenic
      differentiation medium was employed for both the HP and AP groups. Immediately
      before and 1, 2, and 3 weeks after incubation, the scaffolds were harvested for
      histological, immunohistochemical, and gene expression analyses. RESULTS: Cells
      were only found in the AP scaffold surfaces, whereas in the HP group, they were
      distributed evenly throughout the scaffolds. Immunohistochemical analysis
      revealed that the HP group expressed higher levels of osteocalcin (OC),
      osteopontin (OP), osteonectin (ON), and collagen type 1 (Col1) than the AP group
      during the 3-week process. Gene expression analysis revealed that the HP group
      expressed higher levels of ON, Col1, alkaline phosphatase, and integrin beta5
      than the AP group at the 1-, 2-, and 3-week timepoints. The HP group also
      expressed higher levels of core-binding factor alpha-1 (Cbfa1) at the 2- and 3
      week timepoints and higher levels of OP and OC at the 1-week timepoint. Their
      proliferating cell nuclear antigen levels were lower at the 1- and 2-week
      timepoints. CONCLUSIONS: HP enhances cellular viability and improves osteogenic
      differentiation and maturation, although somewhat at the expense of proliferation
      and self-renewal of MSCs. Possible negative effects of the bioprocessor-induced
      HP on bone regeneration were not observed. Further, the mechanotransductive
      molecule integrin beta5 was expressed at high levels after HP stimulation and may
      enhance migration, promote differentiation, and inhibit osteoclast maturation
      during HP-driven osteogenesis in vitro.

PMID- 22607392
TI  - Tissue hypoxaemia causes oedema, inflammation and fibrosis in porcine bronchial
      transsection.
AB  - OBJECTIVES: Bronchial artery revascularization in lung transplantation is
      disputed. This study examined the physiological consequences of porcine bronchial
      transsection and reanastomosis with and without bronchial artery blood supply
      with relation to lung transplantation. DESIGN: Translational, controlled animal
      study. Twelve pigs were operated through a left lateral thoracotomy. The left
      bronchus was transsected and reanastomosed. In the control group (n = 6), the
      bronchial arteries were preserved and in the study group (n = 6) they were
      severed. Bronchial mucosa blood flow (BMBF) was measured with laser-Doppler
      velocimetry and bronchial mucosa haemoglobin saturation and concentration with
      diffuse reflectance spectrophotometry. Measurements were made preoperatively,
      postoperatively and after 1 week. RESULTS: In the study group, left postoperative
      BMBF was significantly lower than preoperatively (115 vs. 210 PU/s, p = 0.0001)
      and lower than in the control group (115 vs. 205 PU/s, p = 0.002). Repeated
      measurement ANOVA showed a significant treatment effect depending on time (p =
      0.0034). The left mucosal haemoglobin saturation in the study group was
      significantly reduced postoperatively, 92% versus 61%, with a treatment effect
      depending on time (p = 0.0080). The reduction in left/right ratio of the mucosal
      haemoglobin concentration 1 week postoperatively in the study group was
      insignificant. CONCLUSION: Bronchial transsection and reanastomosis without
      bronchial artery blood supply was followed by significant decrease in mucosal
      blood flow and saturation postoperatively, and also in tissue haemoglobin
      concentration at section, and provides a physiologic explanation of histological
      changes.

PMID- 22607393
TI  - Repeated neuropsychological assessment in well-controlled epilepsy.
AB  - BACKGROUND: The majority of patients with epilepsy are seizure-free, and repeated
      neuropsychological assessment may be highly relevant in this group. However,
      previous studies have not addressed the possible influence of important clinical
      variables on repeated neuropsychological assessment in this population. METHODS:
      Using data from a large antiepileptic drug (AED) withdrawal study, we calculated
      the neuropsychological practice effects for 139 seizure-free patients with
      epilepsy and analysed the influence of different epilepsy-related factors on
      improvement that were observable 7 months after the initial neuropsychological
      assessment. RESULTS: A clear and significant improvement in neuropsychological
      test performance was found for all the tests employed, regardless of AED
      withdrawal. Furthermore, patients characterized by evidence of brain pathology,
      such as known cerebral aetiology, pathological MRI and pathological EEG, showed
      less practice effects than patients not characterized by these variables. The
      differences were primarily evident for measures of verbal learning and memory.
      CONCLUSION: The data obtained from this study suggest that the development of
      general norms for change in the particular patient population, as well as
      specific norms for change related to important clinical variables, might be
      necessary to be able to determine whether genuine neuropsychological changes have
      occurred in individual patients in this group.

PMID- 22607394
TI  - Oral Rg1 supplementation strengthens antioxidant defense system against exercise
      induced oxidative stress in rat skeletal muscles.
AB  - BACKGROUND: Previous studies reported divergent results on nutraceutical actions
      and free radical scavenging capability of ginseng extracts. Variations in
      ginsenoside profile of ginseng due to different soil and cultivating season may
      contribute to the inconsistency. To circumvent this drawback, we assessed the
      effect of major ginsenoside-Rg1 (Rg1) on skeletal muscle antioxidant defense
      system against exhaustive exercise-induced oxidative stress. METHODS: Forty
      weight-matched rats were evenly divided into control (N = 20) and Rg1 (N = 20)
      groups. Rg1 was orally administered at the dose of 0.1 mg/kg bodyweight per day
      for 10-week. After this long-term Rg1 administration, ten rats from each group
      performed an exhaustive swimming, and remaining rats considered as non-exercise
      control. Tibialis anterior (TA) muscles were surgically collected immediately
      after exercise along with non-exercise rats. RESULTS: Exhaustive exercise
      significantly (p<0.05) increased the lipid peroxidation of control group, as
      evidenced by elevated malondialdehyde (MDA) levels. The increased oxidative
      stress after exercise was also confirmed by decreased reduced glutathione to
      oxidized glutathione ratio (GSH/GSSG ratio) in control rats. However, these
      changes were completely eliminated in Rg1 group. Catalase (CAT) and glutathione
      peroxidase (GPx) activities were significantly (p<0.05) increased by Rg1 in non
      exercise rats, while no significant change after exercise. Nevertheless,
      glutathione reductase (GR) and glutathione S-transferase (GST) activities were
      significantly increased after exercise in Rg1 group. CONCLUSIONS: This study
      provide compelling evidences that Rg1 supplementation can strengthen antioxidant
      defense system in skeletal muscle and completely attenuate the membrane lipid
      peroxidation induced by exhaustive exercise. Our findings suggest that Rg1 can
      use as a nutraceutical supplement to buffer the exhaustive exercise-induced
      oxidative stress.

PMID- 22607395
TI  - Jarisch-Herxheimer reaction among syphilis patients in China.
AB  - BACKGROUND/AIM: The Jarisch-Herxheimer reaction (JHR) is an acute systemic event
      that can occur during the treatment of spirochetal infections, especially
      Treponema pallidum in patients with syphilis. JHR has clinical characteristics of
      an inflammatory reaction to antibiotic treatment and can occur with many
      medications as long as the antitreponemal concentrations are sufficiently high.
      METHODS: The incidence of and risk factors for JHR were investigated
      retrospectively among 1125 patients with syphilis. A total of 357 patients (32%)
      had secondary syphilis, 129 (12%) primary, 178 (16%) early latent, 174 (15%) late
      latent and 285 (25%) latent unknown duration; two patients had tertiary syphilis.
      RESULTS: Sixteen patients (1.4%) developed JHR. All JHRs occurred in patients
      with secondary and latent syphilis treated with penicillin. CONCLUSIONS: JHR
      occurred much less frequently than in previously reported studies. It is
      important that dermatologists recognize the clinical characteristics of JHR so
      that it is not misinterpreted as an allergic reaction to treatment.

PMID- 22607396
TI  - Luteinizing hormone regulates inhibin-alpha subunit expression through multiple
      signaling pathways involving steroidogenic factor-1 and beta-catenin in the
      macaque corpus luteum.
AB  - We employed different experimental model systems to define the role of GATA4,
      beta-catenin, and steroidogenic factor (SF-1) transcriptional factors in the
      regulation of monkey luteal inhibin secretion. Reverse transcription polymerase
      chain reactions and western blotting analyses show high expression of inhibin
      alpha, GATA4, and beta-catenin in corpus luteum (CL) of the mid-luteal phase.
      Gonadotropin-releasing hormone receptor antagonist-induced luteolysis model
      suggested the significance of luteinizing hormone (LH) in regulating these
      transcriptional factors. Inducible cyclic AMP early repressor mRNA expression was
      detected in the CL and no change was observed in different stages of CL.
      Following amino acid sequence analysis, interaction between SF-1 and beta-catenin
      in mid-stage CL was verified by reciprocal co-immunoprecipitation experiments
      coupled to immunoblot analysis. Electrophoretic mobility shift analysis support
      the role of SF-1 in regulating luteal inhibin-alpha expression. Our results
      suggest a possible multiple crosstalk of Wnt, cAMP, and SF-1 in the regulation of
      luteal inhibin secretion.

PMID- 22607397
TI  - Emotional event-related potentials are larger to figures than scenes but are
      similarly reduced by inattention.
AB  - BACKGROUND: In research on event-related potentials (ERP) to emotional pictures,
      greater attention to emotional than neutral stimuli (i.e., motivated attention)
      is commonly indexed by two difference waves between emotional and neutral
      stimuli: the early posterior negativity (EPN) and the late positive potential
      (LPP). Evidence suggests that if attention is directed away from the pictures,
      then the emotional effects on EPN and LPP are eliminated. However, a few studies
      have found residual, emotional effects on EPN and LPP. In these studies, pictures
      were shown at fixation, and picture composition was that of simple figures rather
      than that of complex scenes. Because figures elicit larger LPP than do scenes,
      figures might capture and hold attention more strongly than do scenes. Here, we
      showed negative and neutral pictures of figures and scenes and tested first,
      whether emotional effects are larger to figures than scenes for both EPN and LPP,
      and second, whether emotional effects on EPN and LPP are reduced less for
      unattended figures than scenes. RESULTS: Emotional effects on EPN and LPP were
      larger for figures than scenes. When pictures were unattended, emotional effects
      on EPN increased for scenes but tended to decrease for figures, whereas emotional
      effects on LPP decreased similarly for figures and scenes. CONCLUSIONS: Emotional
      effects on EPN and LPP were larger for figures than scenes, but these effects did
      not resist manipulations of attention more strongly for figures than scenes.
      These findings imply that the emotional content captures attention more strongly
      for figures than scenes, but that the emotional content does not hold attention
      more strongly for figures than scenes.

PMID- 22607398
TI  - Stationary cycling for children with cerebral palsy: does it get them anywhere?

PMID- 22607399
TI  - Genome shuffling of Streptomyces gilvosporeus for improving natamycin production.
AB  - Improvement of natamycin production by Streptomyces gilvosporeus ATCC 13326 was
      performed by recursive protoplast fusion in a genome-shuffling format. After four
      rounds of genome shuffling, the best producer, GS 4-21, with genetic stability
      was obtained and its production of natamycin reached 4.69 +/- 0.05 g/L in shaking
      flask after 96 h cultivation, which was increased by 97.1% and 379% in comparison
      with the highest parental strain pop-72A(r)07 and the initial strain ATCC 13326,
      respectively. Compared with the initial strain ATCC 13326, the recombinant GS 4
      21 presented higher polymorphism. Fifty-four proteins showed differential
      expression levels between the recombinant GS 4-21 and initial strain ATCC 13326.
      Of these proteins, 34 proteins were upregulated and 20 proteins were
      downregulated. Of the upregulated proteins, one protein, glucokinase regulatory
      protein, was involved in natamycin biosynthesis. This comprehensive analysis
      would provide useful information for understanding the natamycin metabolic
      pathway in S. gilvosporeus. 

PMID- 22607400
TI  - Aromatic Base Stacking in DNA: From ab initio Calculations to Molecular Dynamics
      Simulations.
AB  - Abstract   Aromatic stacking of nucleic acid bases is one of the key players in
      determining the structure and dynamics of nucleic acids. The arrangement of
      nucleic acid bases with extensive overlap of their aromatic rings gave rise to
      numerous often contradictory suggestions about the physical origins of stacking
      and the possible role of delocalized electrons in stacked aromatic pi systems,
      leading to some confusion about the issue. The recent advance of computer
      hardware and software finally allowed the application of state of the art quantum
      mechanical approaches with inclusion of electron correlation effects to study
      aromatic base stacking, now providing an ultimitate qualitative description of
      the phenomenon. Base stacking is determined by an interplay of the three most
      commonly encountered molecular interactions: dispersion attraction, electrostatic
      interaction, and short-range repulsion. Unusual (aromatic- stacking specific)
      energy contributions were in fact not evidenced and are not necessary to describe
      stacking. The currently used simple empirical potential form, relying on atom
      centered constant point charges and Lennard-Jones van der Waals terms, is
      entirely able to reproduce the essential features of base stacking. Thus, we can
      conclude that base stacking is in principle one of the best described
      interactions in current molecular modeling and it allows to study base stacking
      in DNA using large-scale classical molecular dynamics simulations. Neglect of
      cooperativity of stacking appears to be the most serious approximation of the
      currently used force field form.   This review summarizes recent developments in
      the field. It is written for an audience that is not necessarily expert in
      computational quantum chemistry and follows up on our previous contribution
      (Sponer et. al., J. Biomol. Struct. Dyn. 14, 117, (1997)). First, the applied
      methodology, its accuracy, and the physical nature of base stacking is briefly
      overviewed, including a comment on the accuracy of other molecular orbital
      methods and force fields. Then, base stacking is contrasted with hydrogen
      bonding, the other dominant force in nucleic acid structure. The sequence
      dependence and cooperativity of base stacking is commented on, and finally a
      brief introduction into recent progress in large-scale molecular dynamics
      simulations of nucleic acids is provided. Using four stranded DNA assemblies as
      an example, we demonstrate the efficacy of current molecular dynamics techniques
      that utilize refined and verified force fields in the study of stacking in
      nucleic acid molecules.

PMID- 22607401
TI  - Molecular biology of light transduction by the Mammalian photoreceptor,
      rhodopsin.
AB  - Abstract   Rhodopsin, the vertebrate photoreceptor, is a prototypic molecule in
      the largest family of G- protein coupled receptors (GPCR). Like all receptors of
      this family, it contains three distinct domains: the cytoplasmic (intracellular)
      domain that is involved in all the protein-protein interactions; the
      transmembrane (TM) domain where the signal transduction begins, by light-
      catalysed isomerization of 11-cis-retinal to all trans-retinal, and the
      intradiscal domain which appears to be involved in a specific tertiary structure.
      The main focus of this talk is to describe efforts to understand specific
      structure and function in each domain. The main findings to be presented are as
      follows: 1. Intradiscal domain contains a globular tertiary structure. A central
      feature is a disulfide bond (Cys110-Cys187) which is conserved in most of the
      known GPCR. 2. The correct folding in vivo requires the formation of the above
      disulfide bond. Misfolding resulting in non-retinal binding is frequently caused
      by Retinitis Pigmentosa (RP) point mutations in the intradiscal and the TM
      domain. 3. In vivo folding studies, using RP mutations in every one of the seven
      helices, have shown that the packing of the helices in the TM domain and folding
      to form the intradiscal tertiary structure are coupled. 4. Cysteine mutagenesis
      has been used systematically to study the tertiary structure and light-dependent
      changes throughout the cytoplasmic face by combination of biochemical and
      biophysical studies. In particular, EPR spectroscopy following spin labeling of
      selected double cysteine mutants has shown movements in helices, including
      tilting, following retinal isomerization. 5. Large scale expression of mutants
      has allowed application of both (19)F-NMR (solution) and MAS solid state NMR (in
      collaboration with Dr. Steve Smith's group, SUNY, Stony Brook). Results of
      current work are promising for detailed study of the conformational change.
      Finally, a unifying hypothesis, which is termed the central dogma in the GPCR
      field, will be proposed. This states that despite the enormous variation in
      "accessory" structural details, the principal mechanism of signal transduction
      starting with pertubation in the seven helical bundle is fundamentally the same
      in all GPCRs. Experiments to test helix movements, the first step in signal
      transduction following ligand binding in two adrenergic receptors are now
      feasible. The patterns of helix movements in them will be compared with the
      pattern demonstrated for rhodopsin and its mutants.

PMID- 22607402
TI  - Ligand selectivity by nuclear hormone receptors.
AB  - Abstract   Numerous crystal structures of nuclear receptor ligand binding domains
      (LBDs) are known. The retinoic acid (RAR) and estrogen (ER) receptors are the two
      members for which a large set of agonists and antagonist complexes are available.
      Their analysis reveals key features of the RAR and ER ligand binding pocket (LBP)
      responsible for ligand selectivity. The RAR LBD exhibits a rigid architecture to
      which the ligand has to adapt, whereas the ER LBD can accomodate numerous ligands
      of variable shapes.

PMID- 22607403
TI  - Aminoacylation at the Atomic Level in Class IIa Aminoacyl-tRNA Synthetases.
AB  - Abstract   The crystal structures of histidyl- (HisRS) and threonyl-tRNA
      synthetase (ThrRS) from E. coli and glycyl-tRNA synthetase (GlyRS) from T.
      thermophilus, all homodimeric class IIa enzymes, were determined in enzyme
      substrate and enzyme-product states corresponding to the two steps of
      aminoacylation. HisRS was complexed with the histidine analog histidinol plus ATP
      and with histidyl-adenylate, while GlyRS was complexed with ATP and with glycyl
      adenylate; these complexes represent the enzyme-substrate and enzyme-product
      states of the first step of aminoacylation, i.e. the amino acid activation. In
      both enzymes the ligands occupy the substrate-binding pocket of the N-terminal
      active site domain, which contains the classical class II aminoacyl-tRNA
      synthetase fold. HisRS interacts in the same fashion with the histidine,
      adenosine and alpha-phosphate moieties of the substrates and intermediate, and
      GlyRS interacts in the same way with the adenosine and alpha-phosphate moieties
      in both states. In addition to the amino acid recognition, there is one key
      mechanistic difference between the two enzymes: HisRS uses an arginine whereas
      GlyRS employs a magnesium ion to catalyze the activation of the amino acid. ThrRS
      was complexed with its cognate tRNA and ATP, which represents the enzyme
      substrate state of the second step of aminoacylation, i.e. the transfer of the
      amino acid to the 3'-terminal ribose of the tRNA. All three enzymes utilize class
      II conserved residues to interact with the adenosine-phosphate. ThrRS binds
      tRNA(Thr) so that the acceptor stem enters the active site pocket above the
      adenylate, with the 3'-terminal OH positioned to pick up the amino acid, and the
      anticodon loop interacts with the C-terminal domain whose fold is shared by all
      three enzymes. We can thus extend the principles of tRNA binding to the other two
      enzymes.

PMID- 22607404
TI  - RNA scaffolds for minihelix-based aminoacyl transfer: design of
      "transpeptizymes".
AB  - Abstract   Some evidence and considerations suggest that RNA minihelices based on
      the acceptor-TPsiC stem-loop of tRNAs are the historical, more ancient part of
      the tRNA structure. These minihelices are substrates for aminoacylation by tRNA
      synthetases. In the transition from the RNA world to the theatre of proteins,
      aminoacyl minihelices may have had a role in early systems of peptide synthesis.
      Such systems would require bringing together aminoacyl groups into close
      proximity in order for peptide bonds to form. Here we report the design of RNA
      scaffolds based on pieces of the structure of the P4-P6 domain of the Tetrahymena
      ribozyme. RNA minihelices were incorporated into these scaffolds and the
      resulting RNAs could be enzymatically aminoacylated. The RNA scaffolds containing
      the minihelix-like pieces associated spontaneously to create the presumptive P4
      P6 structure and thereby bring together the substrates for aminoacylation. Thus,
      peptide synthesis with associating RNA scaffolds that contain minihelix-like
      motifs appears plausible.

PMID- 22607405
TI  - Structural Studies of Model RNA Helices with Relevance to Aminoacyl-tRNA
      Synthetase Specificity and HIV Reverse Transcription.
AB  - Abstract   We describe high-resolution crystal structures of synthetic nucleic
      acid fragments determined as part of an effort to understand determinants of
      sequence-specific protein binding on the level of double-helix structure. In a
      first set of experiments, 7-base-pair RNA duplexes representing the acceptor-stem
      helix of Escherichia coli tRNA(Ala) and variants thereof were characterized at
      atomic resolution. The structures revealed a standard A-form double helix locally
      perturbed by a G.U wobble base pair at sequence position 3/70 of the tRNA. The
      G.U pair shows a characteristic hydration pattern which must be considered an
      integral part of the double-helix structure. It does not seem to exert a global
      effect on the duplex structure. A second experiment concerned the chimeric DNA
      RNA hybrid structure formed transiently during initiation of minus-strand
      synthesis by the reverse transcriptase of HIV-1. The crystal structure of an 8
      base-pair duplex with an RNA template strand derived from HIV-1 and a
      complementary strand representing the junction between the tRNA(Lys,3) RNA primer
      and the newly synthesized DNA strand was solved at a resolution of 1.9 A. As
      before, the double helix was found to adopt standard A-type conformation with
      only local variations of backbone conformation. Based on the global helix
      structure as present in the crystal, it remains difficult to explain the
      preference of the reverse-transcriptase-associated RNAse H activity for certain
      sites of the template strand. Structural plasticity near the main cleavage site
      in suggested to govern cutting preferences. In both systems investigated,
      structural studies by NMR spectroscopy were carried out by others in parallel. In
      both cases, the solution structures are in partial disagreement with the
      crystallographic results by describing a significantly higher level of deviation
      from the canonical A-conformation.

PMID- 22607406
TI  - Relating the Structure of HIV-1 Reverse Transcriptase to Its Processing Step.
AB  - Abstract   By treating an enzyme as a coarse-grained uniform block of material,
      utilizing only the alpha-Carbon positions, the normal modes of motion can be
      obtained. For reverse transcriptase the slower of these motions are suggestive of
      being involved in the processing step, where the RNA or DNA strand is copied onto
      a new DNA strand at a polymerase site, and the RNA strand is subsequently cut up
      at the distant Ribonuclease H site. The slowest mode of motion involves hinge
      bending about a site midway between the polymerase and Ribonuclease H sites,
      suggesting that it can push or pull the RNA strand between these two sites.
      Pulling the nucleic acid strand would require tight binding to the RNase H site.
      The next slowest mode involves a hinge that opens and closes the protein like a
      clamp, which could facilitate the release of the nucleic acids for their step
      wise progression. The third mode could rotate the substrate. An overall
      description of the step-wise processing step would involve close coordination
      among these steps. Results suggest that the smaller p51 subunit serves only as
      ballast to support the various modes of motion involving the different parts of
      the p66 subunit.

PMID- 22607407
TI  - Solution Structure of an Antibody-Bound HIV-1(IIIB) V3 Peptide: A Cis Proline
      Turn Linking Two beta-hairpin Strands.
AB  - Abstract   The refined solution structure of a peptide representing the full
      epitope of the HIV-1(IIIB) V3 loop in complex with the anti-gp120 antibody Fv
      fragment was determined using isotope-filtered and isotope-edited NMR. Both the
      (15)N-labeled peptide in complex with the unlabeled Fv and the unlabeled peptide
      complexed with the uniformly (15)N,(13)C-labeled Fv were investigated. The
      backbone of the bound peptide adopts a well defined beta-hairpin conformation
      with two twisted anti-parallel beta-strands linked by a type VI tight turn
      comprising residues RGPG. The central glycine and proline residues of the turn
      are linked by a cis peptide bond. (15)N{(1)H} NOE measurements demonstrated that
      the backbone of the bound peptide including the central QRGPGR loop is well
      ordered in the bound state. The V3 loop peptide solution structure is
      significantly different from the peptide conformation in the X-ray structures of
      three anti-peptide antibody/V3(MN) peptide complexes. These differences seem to
      be dictated by the antibody dependence and HIV strain-specificity of the V3
      peptide fold.

PMID- 22607408
TI  - A conserved asparagine makes an essential contact to an RNA adenosine or
      cytidine.
AB  - Abstract   Post-transriptional regulation of yeast ribosomal protein L30, RPL30,
      requires the formation of a complex comprised of RPL30 and its RNA transcript [J.
      Vilardell and J. R. Warner, Genes & Dev. 8, 211-220 (1994)]. Mutational analysis
      of both the RNA and the protein reveals that an asparagine-adenosine contact is
      important. Replacement of the asparagine by alanine weakens binding dramatically,
      but substitution of the adenosine by cytidine or guanosine slightly increases or
      decreases respective binding affinities for RPL30. The structure of the complex
      has been solved by NMR and shows a conserved asparagine in position to form two
      hydrogen bonds with adenosine's Watson-Crick face [H. Mao, S. A. White and J. R.
      Williamson, Nat. Struct. Biol. 6, 1139-1147 (1999)]. Asparagine is necessary for
      this interaction but relatively small differences in binding affinity are
      measured for three different nucleotides.

PMID- 22607409
TI  - Contribution of salt bridges toward protein thermostability.
AB  - Abstract   We present an extensive study of the structural factors suggested to
      be responsible for thermostability, in 18 nonredundant families of thermophilic
      and mesophilic proteins. Each of these 18 families consists of homologous
      thermophilic-mesophile pairs, with high resolution crystal structures for both
      pair-members available in the Protein Data Bank (PDB). We observe that both the
      thermophilic and the mesophilic proteins have similar hydrophobicities,
      oligomeric states, and hydrogen bonds. On the other hand, salt bridges increase
      in most of the thermophilic proteins. Yet, on the other hand, salt bridges have
      been proposed to destabilize protein structures. Hence, here we seek to
      understand why do salt bridges occur more frequently in thermophilic proteins.
      Investigating this problem, we focus on the glutamate dehydrogenase family.
      Computation of the electrostatic contribution of salt bridge energies by solving
      the Poisson equation in a continuum solvent medium, shows that the salt bridges
      in the glutamate dehydrogenase from the hyperthermophile Pyrococcus furiosus are
      highly stabilizing. In contrast, the salt bridges in the mesophilic Clostridium
      symbiosum glutamate dehydrogenase contribute only marginally to protein
      stability. The presence of a larger number of salt bridges cooperatively enhances
      their strength. Our results indicate that salt bridges and their networks may
      have an important role in rigidifying the protein structure at high temperatures.
      Formation of salt bridge networks may help in explaining the increased occurrence
      and stability of salt bridges in hyperthermophiles.

PMID- 22607410
TI  - Globularity and protein function.
AB  - Abstract   The forces that direct protein folding lead naturally to native
      proteins and protein domains that are typically, to a first approximation,
      globular-spherical and compact, with a relatively clear distinction between the
      hydrophobic inside and polar outside. The near-universality of these features of
      protein structures sharpens our focus on some apparent exceptions. Consideration
      of the structure/function link in some of the exceptional cases provides some
      insights into our views of protein function.

PMID- 22607411
TI  - Modeling molecular recognition: theory and application.
AB  - Abstract   Efficient, reliable methods for calculating the binding affinities of
      noncovalent complexes would allow advances in a variety of areas such as drug
      discovery and separation science. We have recently described a method that
      accommodates significant physical detail while remaining fast enough for use in
      molecular design. This approach uses the predominant states method to compute
      free energies, an empirical force field, and an implicit solvation model based
      upon continuum electrostatics. We review applications of this method to systems
      ranging from small molecules to protein-ligand complexes.

PMID- 22607412
TI  - Aromatic Ring Currents at a Protein Surface: Use of (1)H-NMR Chemical Shifts to
      Refine the Structure of a Naked beta Sheet.
AB  - Abstract   The naked beta sheet, a newly recognized motif of protein structure,
      exhibits ordered surfaces in the absence of a conventional hydrophobic core. A
      model is provided by an archaeal Zn ribbon homologous to eukaryotic RNA
      polymerase II subunit 9 (RPB9). This subunit, which regulates transcriptional
      start-site selection and downstream pausing, contains Zn(2+)-binding motifs
      similar to those of general transcription factors TFIIB and TFIIS. Interestingly,
      distance-geometry yields two models of the archaeal Zn ribbon differing in the
      orientation of a conserved tyrosine side chain on the well-ordered surface of the
      naked beta-sheet. The models are equally consistent with conventional restraints
      and otherwise contain indistinguishable structural features, including a
      tetrahedral Cys(4) Zn(2+)-binding sites, four antiparallel beta-strands, and
      disordered loop. Due to the change in tyrosine orientation and correlated changes
      in the configuration of neighboring side chains, the two models predict
      inequivalent patterns of aromatic ring-current shifts. The observed secondary
      shifts of adjoining resonances are shown to be consistent with one model but not
      the other. In the consistent model the surface of the beta-sheet contains
      successive aromatic edge-to-face contacts in accord with semi-classical and ab
      initio potentials. We speculate that the aromatic-rich surface of the
      hyperthermophilic RPB9 domain contributes its thermodynamic stability and
      provides a nucleic-acid-binding site in the eukaryotic and archaeal
      transcriptional machinery. The present study demonstrates how the reduced
      dimensionality of a surface can lead to ambiguities in the interpretation of
      nuclear Overhauser enhancements. The results illustrate the utility of chemical
      shifts at such a surface in the cross-validation of a high-resolution solution
      structure.

PMID- 22607413
TI  - How Do Hydrogen Bonds Contribute to Protein-DNA Recognition?
AB  - Abstract   The average strength of hydrogen bonding interactions at the interface
      of 40 protein-DNA complexes comprising ~ 1500 potential hydrogen bonds and their
      free energies of formation have been estimated employing some recent advances in
      theoretical treatments of electrostatic interactions. The hydrogen bond spatial
      frequency distribution shows a maximum at a proton-acceptor distance of 2.1A. The
      corresponding average interaction energy and the binding free energy are computed
      to be -1 kcal and +4 kcal/mol.H-bond respectively. Thus hydrogen bonds do not
      appear to provide the driving force for the formation of specific complexes from
      initially separated protein and DNA but serve to optimize the interactions in the
      specific complex once it is formed, via distance and angle requirements.

PMID- 22607414
TI  - Structure and dynamics of the tetrameric mnt repressor and a model for its DNA
      complex.
AB  - Abstract   The tetrameric Mnt repressor of bacteriophage P22 consists of two
      dimeric DNA-binding domains and a tetramerization domain. The NOE and chemical
      shift data demonstrate that the structures of the domains in the wild-type
      repressor protein are similar to those of the separate domains, the three
      dimensional structures of which have been determined previously. (15)N relaxation
      measurements show that the linker that connects the anti-parallel four-helix
      bundle with the two beta-sheet DNA-binding dimers is highly flexible. No evidence
      was found for interactions between the distinct modules. The (15)N relaxation
      properties of the two domains differ substantially, confirming their structural
      independence. A model in which one two-stranded coiled coil of the four-helix
      bundle is attached to one N-terminal dimer is most consistent with the
      biochemical data and (15)N relaxation data. For the Mnt-DNA complex this geometry
      fits with a model in which the two beta-sheet DNA-binding domains are bound at
      two successive major grooves of the Mnt operator and the tetramerization domain
      is packed between these two DNA-bound dimers. In such a model the two-fold
      symmetry axis of the four-helix bundle coincides with that of the operator
      sequence and the two bound dimers. Bending of the Mnt operator of approximately
      30 degrees  upon binding of the tetramer, as measured by gel-shift assays, is in
      agreement with this model of the Mnt-DNA complex.

PMID- 22607415
TI  - How Do Proteins Recognize DNA? Solution Structure and Local Conformational
      Dynamics of Lac Operators by 2D NMR.
AB  - Abstract   The NMR structures of the symmetrical lac operator DNA fragment,
      d(TGTGAGCGCTCACA)(2) and it's mutant, d(TATGAGCGCTCATA)(2), were determined by
      the MORASS hybrid relaxation matrix/restrained molecular dynamics methodology.
      The (1)H chemical shifts of nearly all of the non-exchangeable protons were
      assigned using standard two-dimensional NMR techniques. Ultimately, 181 NOE
      volumes/strand were used in the final MORASS structural determination for each
      molecule. Both model built A- and B-form DNA starting geometries were used which
      converged to final structures giving 1.85A and 1.32A RMSD for the wild-type and
      mutant operators respectively. An excellent agreement between experimental NOESY
      data with that calculated from the final structures was achieved. The sequence
      dependence of the DNA backbone torsional angle conformational dynamics was
      further examined using trajectories from four 500 ps AMBER PMES molecular
      dynamics calculations performed on the final NMR structures. These are discussed
      as well as the experimental vs. calculated JH3'-P coupling constants and their
      relation to backbone dynamics.

PMID- 22607416
TI  - Role of the N- and C- terminal dimer interfaces of 434 repressor in recognizing
      sequence-dependent DNA structure.
AB  - Abstract   The binding of proteins to specific DNA sequences plays a central role
      in the regulation of gene expression. Crucial to understanding how these proteins
      exert their effects is insight into the structure and flexibility of the protein
      DNA complex. Over the past several years much has been learned about how the
      intimate contacts made between proteins and DNA enable proteins to recognize and
      bind with high specificity only to their cognate DNA binding sites. Studies
      conducted in our laboratory have shown that sequence-specific binding of DNA by
      proteins not only involves the close approach of amino acids and base pairs in
      the binding site, but also that base pairs not in contact with the protein affect
      binding and specificity through sequence-specific effects on DNA structure. The
      direct reading of the DNA sequence by proteins occurs by chemical complementarity
      between the interacting groups. Proper alignment of the interacting surfaces of
      functional groups on the protein and DNA molecules is crucial to the formation of
      stable and specific protein-DNA complexes. In many cases, the appropriate
      juxtaposition of the chemically complementary groups requires mutual adjustments
      in the structure of protein and DNA. Failure to do so can result in loss of
      affinity, loss of specificity or both. Together, the dimer interface and
      noncontacted bases within or adjacent to the binding site direct the structural
      complementarity between the functional groups on the protein and DNA.

PMID- 22607417
TI  - Geometry of the DNA Substrates in Cre-loxP Site-Specific Recombination.
AB  - Abstract   Cre recombinase is a member of a large family of site-specific
      recombination enzymes that performs a cut-and-paste operation between two
      specific DNA sequences. Our goal has been to understand the mechanism of this
      complex reaction by trapping and characterizing the three-dimensional structures
      of each of the reaction intermediates. This work has led to high resolution
      crystallographic models of (i) the initial synaptic complex, (ii) the covalent
      Cre- DNA intermediate, and (iii) the Holliday junction intermediate. The Cre-loxP
      system appears to function by creating at the outset a protein-DNA architecture
      that resembles that of the Holliday junction intermediate that is eventually
      formed. The "arms" of the loxP sites are initially bent by about 75 degrees  in
      the synaptic complex, forming a nearly planar arrangement that is held fixed,
      while cleavage and strand exchange occur in the central region between the arms.
      The simplest view of the recombination pathway is that it contains two
      symmetrical halves, each of which uses this Holliday junction-like architectural
      framework to mediate the cleavage and ligation steps. The two halves are linked
      by a subtle isomerization of the Holliday intermediate that switches the roles of
      the recombinase subunits and allows exchange of the second pair of DNA strands.
      In this paper, we summarize recent structural results from our laboratory, with
      an emphasis on the geometry of the DNA substrates.

PMID- 22607418
TI  - A Mechanism for RecA-Promoted Sequence Homology Recognition and Strand Exchange
      Between Single-Stranded DNA and Duplex DNA, via Triple-Helical Intermediates.
AB  - Abstract   A central function of RecA protein during homologous recombination is
      to promote sequence recognition and strand exchange between a stretched and
      unwound single-stranded DNA, to which it is complexed, and a duplex DNA. By
      studying the properties of DNA under the conditions of deformation imposed by
      RecA, we propose a model for recognition and strand exchange at the atomic level,
      via unusual triple-helical intermediates. In this model, association takes place
      within a stretched and unwound triple helix of a new type, where the invading
      single strand occupies the minor groove of the duplex in a parallel orientation.
      Our calculations indicate that strand exchange within this structure is
      exothermic and results in a triple helix where the third strand interacts in the
      major groove, the so-called R-DNA triple helix. Preliminary calculations suggest
      that sequence homology recognition within the triplex of association is partial
      and that it is completed during strand exchange and product formation.

PMID- 22607419
TI  - DNA and RNA folds in transcription complex as evidenced by iodine-125
      radioprobing.
AB  - Abstract   Folding of the DNA and RNA strands in an arrested T7 RNA polymerase
      (RNAP) transcription complex was studied by radioprobing, a novel method based on
      an analysis of the strand breaks produced by decay of the iodine-125 incorporated
      at the C5 position of cytosine. (125)I-labeled cytosines were incorporated into
      transcripts at different positions relative to the site of the arrest. The
      intensities of the DNA breaks inversely correlate with the distances from the
      (125)I decay site, so the radioprobing data provide information about the spatial
      RNA/DNA folding during transcription.   We found that the yield of DNA strand
      breaks is significantly higher in the template than the non-template strand. This
      is consistent with local opening of the DNA duplex and formation of a hybrid
      between RNA and the template DNA strand. Our data demonstrate that the RNA-DNA
      hybrid has a nonuni form A-like structure. When the (125)I is incorporatedseven
      nucleotides from the active center of RNAP, the yield of strand breaks is
      substantially lower than if (125)I is positioned at the ends of the hybrid.
      Consequently, the DNA and RNA strands are located closer to each other at the
      ends of the hybrid and somehow separated in the middle. Surprisingly, the (125)I
      induced breaks were detected in both DNA strands upstream from the transcription
      "bubble" indicating that DNA and RNA are closely associated outside the RNAP
      cleft.   Thus, radioprobing data imply that the RNA/DNA fold in the complex with
      T7 RNAP is more complicated than had been anticipated by the existing models.
      Based on the present data, we suggest a sterically feasible model explaining how
      formation of the long RNA-DNA hybrid can result in the initiation-to-elongation
      switch in the T7 transcription complex. According to this model, the topological
      linkage between the DNA and RNA strands provides the necessary stability for the
      elongation complex, while permitting movement of the polymerase along the DNA
      duplex.

PMID- 22607420
TI  - DNA Structure and Polymerase Fidelity: A New Role for A-DNA.
AB  - Abstract   Although the recent structural studies on polymerases have brought new
      insights on polymerase fidelity, the role of DNA sequence and structure is not
      well understood. Here, the analysis of the crystal structures of hotspots for
      polymerase slippage shows that, in the B- form, these sequences share common
      structural alterations which may explain the high rate of replication errors. In
      (CA)(n) tracts, a "Janus-like" structure with shifted base pairs in the major
      groove but an apparent normal geometry in the minor groove constitutes a
      molecular decoy which can mislead the polymerases. A model of the rat polymerase
      beta bound to this structure suggests that an altered conformation of the nascent
      template-primer duplex can interfere with correct nucleotide incorporation by
      affecting the geometry of the active site and breaking the rules of base pairing
      while at the same time escaping enzymatic mechanisms of error discrimination
      scanning for the correct geometry of the minor groove. In contrast, by showing
      that the A-form greatly attenuates the sequence-dependent structural alterations
      in hotspots, this study reveals that the A-conformation of the nascent template
      primer duplex at the vicinity of the polymerase active site will contribute to
      fidelity. The A-form may play the role of a structural buffer which preserves the
      correct geometry of the active site for all sequences. The comparison of the
      conformation of the nascent template-primer duplex in five available crystal
      structures of DNA polymerase-DNA complexes shows indeed that polymerase beta the
      least accurate enzyme, is unique in binding to a B-DNA duplex even close to its
      active site. This model leads to several predictions which are discussed in the
      light of published experimental data.

PMID- 22607421
TI  - Effects of Oxidation Agents and Metal Ions on Binding of p53 to Supercoiled DNA.
AB  - Summary   Wild type human full length (f.1.) tumor suppressor p53 protein binds
      preferentially to super-coiled (sc) DNA in vitro both in the presence and absence
      of the p53 consensus sequence (p53CON). This binding produces a ladder of
      retarded bands on the agarose gel. Bands revealed by immunoblotting with antibody
      DO-1 corresponded to the ethidium stained retarded bands. The intensity and the
      number of bands of p53-scDNA complex were decreased by physiological
      concentrations of unchelated zinc ions. Nickel and cobalt ions inhibited binding
      of p53 to scDNA and to p53CON in linear DNA fragments less efficiently than zinc.
      Compared to the intrinsic zinc strongly bound to Cys 176, Cys 238, Cys 242 and
      His 179 in the p53 core domain, binding of additional Zn(2+) to p53 was much
      weaker as shown by an easy removal of the latter ions by low concentrations of
      EDTA. Oxidation of the protein with diamide resulted in a decrease of the number
      of the retarded bands. Under the same conditions, no binding of oxidized p53 to
      p53CON in a linear DNA fragment was observed. In agreement with the literature
      oxidation of f.1. p53 with diamide was irreversible and was not reverted by an
      excess of DTT. We showed that in the presence of 0.1 mM zinc ions, oxidation of
      p53 became reversible. Other divalent cations tested (cadmium, cobalt, nickel)
      exhibited no such effect. We suggested that the irreversibility of p53 oxidation
      was due, at least in part, to the removal of intrinsic zinc from its position in
      the DNA binding domain (after oxidation of the three cysteines to which the zinc
      ion is coordinated in the reduced protein) accompanied by a change in the p53
      conformation. Binding of C-terminal anti-p53 antibody also protected bacterially
      expressed protein against irreversible loss of activity due to diamide oxidation.
      Binding the human p53 core domain (segment 94-312) to scDNA greatly differed from
      that observed with the full-length p53. The core domain did not posses the
      ability to bind strongly to many sites in scDNA regardless of the presence or
      absence of p53CON suggesting involvement of some other domain (probably C
      terminal) in binding of the full-length p53 to scDNA. Supershift experiments
      using antibodies against p53 N- or C-terminus suggested that in oxidized p53,
      scDNA binding through the C-terminus gained importance.

PMID- 22607422
TI  - The atomic structure of the nucleosome core particle.

PMID- 22607423
TI  - Crystal Structure of an RNA Duplex [r(gugcaca)dC](2) with 3'-Dinucleoside
      Overhangs Forming a Superhelix.
AB  - Abstract   Crystal structure of the RNA octamer duplex, [r(gugcaca)dC] (2), with
      space group I2(1)2(1)2(1) and the cell constants a=24.29, b=45.25 and c=73.68A,
      has been determined and refined. The structural and packing architecture of the
      molecule consist of a highly bent six base paired duplex forming a right-handed
      superhelix stacked in tandem compared to an infinite pseudo- continuous column as
      is usually present in RNA crystal structures. The super helix could be formed by
      the head-to-head stacking (g1 over g1 and g9 over g9), the large bend and the
      twists at the junctions may also be responsible. The sugar-phosphate backbones of
      the 3'-end dinucleoside overhangs snuggly fit into the minor grooves of adjacent
      double helical stacks. The 3'-terminal deoxycytidines form antiparallel
      hemiprotonated trans (C.C)(+) pairs with symmetry related deoxycytidines, while
      the penultimate adenines form base triples (a*g.c) with the capping g.c base
      pairs of the hexamer duplex with the adenine (a7) at one end being syn and at the
      other anti. These triple interactions are the same as those found in the
      tetrahymena ribozyme and group I intron.

PMID- 22607424
TI  - The Early Folding Intermediates of the Tetrahymena Ribozyme are Kinetically
      Trapped.
AB  - Abstract   The "RNA folding problem" is a fundamental and challenging question in
      contemporary biophysics. Understanding the mechanism(s) by which RNA molecules
      fold into compact structures capable of biological activity is important because
      RNA folding is closely tied to cellular regulation and metabolism and catalytic
      RNAs are potential reagents for gene therapy. Unlike the "protein folding
      problem" which has been under study for many decades, the study of RNA tertiary
      structure stability and folding is a relatively new field of endeavor. Thus, a
      detailed understanding of both the thermodynamics and kinetics of RNA folding are
      only now beginning to emerge.   Kinetic traps have been observed in the late
      folding steps of the Tetrahymena ribozyme. In this study we extend our
      "synchrotron footprinting" analysis of the Tetrahymena ribozyme (Sclavi, et al.
      Science 279, 1940-1943, 1998) to probe the potential presence of kinetic traps in
      other steps in the folding mechanism. Examination of the folding in 3M urea
      demonstrates a significant increase in the rates of folding for early folding
      steps in the formation of the ribozyme tertiary structure. These data support the
      conclusion of Williamson and co-workers that the rate-limiting step in the
      folding of the Tetrahymena ribozyme is kinetically trapped by native interactions
      (Rook et al., J. Mol. Bio., 281, 609-620, 1998). Kinetic trapping also occurs in
      the formation of intermediates earlier in the folding reaction, and in these
      cases nonnative interactions may also play a role in the barrier to folding.

PMID- 22607425
TI  - Three-dimensional RNA structure-based drug discovery.
AB  - Abstract   We have initiated a program to develop promising drug candidate leads
      using a new drug discovery paradigm based on three-dimensional RNA-structure
      based computational screening of about 200,000 commercially available compounds
      for binding to selected RNA targets. As our first endeavor, we are using the
      three-dimensional structure of portions of the HIV-1 genome. Candidate lead
      compounds we seek are water-soluble, nonpeptide, nonnucleotide organic compounds
      generally with molecular weight less than 500 daltons. Structural studies of
      complexes formed with potential leads and their RNA targets should eventually
      yield insight into features governing affinity and specificity. The promising
      leads identified by virtual screening are tested for inhibition in functional
      assays. Leads will be selected for further development via computational and
      experimental combinatorial chemistry.

PMID- 22607426
TI  - Bridging the prebiotic and RNA worlds: prebiotic RNA synthesis on clay.
AB  - Abstract   Progress towards the laboratory demonstration of the steps in the
      prebiotic origin of the RNA world is reviewed. Montmorillonite clay catalyzes the
      formation of RNAs containing 6-14 monomer units from the activated
      mononucleotides of A, C, G, I and U. The RNAs formed have 3', 5'- and 2', 5'
      links, pyrophosphate links and have both linear and cyclic chains. The purine
      oligonucleotides have more 3', 5'- links while the pyrimidine nucleotides have
      more 2', 5'-linkages. Template-directed synthesis on the heterogeneous oligo(C)s
      formed on mont- morillonite yields the corresponding oligo(G)s. The dimer
      fraction formed in the reaction of a binary mixture of a purine and pyrimidine
      nucleotide shows sequence selectivity with about a 20 fold excess of the 5'
      purine-pyrimidine dimer over that of the 5'-pyrimidine-purine dimer. RNAs as long
      as 50 mers are formed by the elongation of a decamer bound to montmorillonite by
      the daily addition of activated monomer to it over a 14-day time period.

PMID- 22607427
TI  - Synthesis of specifically deuterated nucleotides for NMR studies on RNA.
AB  - Abstract   We propose a strategy for NMR structure determination of RNA based on
      deuteration and use of specific labeling patterns. This strategy involves the use
      of NTPs that are deuterated in the ribose ring except for specific positions,
      e.g. H2', and that are either unlabeled or uniformly labeled in (13)C and (15)N
      in either the ribose or the base or both. Incorporation of these NTPs into an RNA
      sequence reduces both resonance line-width and spectral overlap. A limited number
      of combinations of these differently labeled NTPs in an RNA sequence suffices to
      obtain all relevant proton resonance assignments and structure parameters
      necessary for structure determination of larger systems (? 50 nucleotides). We
      describe the in vitro synthesis of the deuterated and/or (13)C/(15)N-labeled NTPs
      from glucose via separate enzymatic reactions. First, enzymes from the pentose
      phosphate pathway efficiently convert glucose into ribose and enzymes from
      nucleotide biosynthesis and salvage pathways subsequently convert the ribose into
      nucleosides triphosphates (NTPs). The enzymes from the pentosephosphate pathway
      are all commercially available; the remaining enzymes have been purified from
      over-expressing strains. Separate enzymatic reactions were used to convert
      (2)H(7)- (13)C(6)-glucose into [1',3',4',5',5"-(2)H(5)-1',2',3',4',5',2,4,5,6
      (13)C(9)-1,3-(15)N(2)]UTP and (2)H(7)-glucose into [1',3',4',5',5"-(2)H(5)]ATP,
      [1',3',4',5',5"-(2)H(5)]GTP, and [1',3',4',5',5"-(2)H(5)] CTP. The synthesis
      yields up to 1 gram of NTPs from 1 gram of glucose, which is about 5 to 10 times
      as efficient extraction for E. Coli grown on glucose. The synthesis presented
      here, is a modification of the method described by Tolbert & Williamson (1,2).
      (1)D and (2)D NMR spectra were acquired to demonstrate the utility of the new
      labeling patterns. The enzymatically synthesized NTPs were used in the synthesis
      of a 31-nucleotide RNA derived from the primer binding site of Hepatitis B virus
      genomic RNA to asses their efficiency in transcription.

PMID- 22607428
TI  - An earring for the double helix: assembly of topological links comprising duplex
      DNA and a circular oligodeoxynucleotide.
AB  - Abstract   Novel DNA nanostructures, locked pseudorotaxane and locked catenane
      were assembled through topological linkage of a double-stranded target to a
      circular oligodeoxyribonucleotide (cODN)(+). The formation of these
      supramolecular complexes occurs with remarkable sequence specificity and is
      accomplished via local opening of duplex DNA by a pair of homopyrimidine bis
      PNAs. The obtained cODN label, resembling an earring, forms a true topological
      link with the linear or closed circular (cc) target DNA and occupies a fixed
      position along the double helix. The PNA directed assembly described here
      introduces PNA oligomers into the repertoire of DNA nanotechnological tools.

PMID- 22607429
TI  - Targeting of Pu.Py Duplexes by GA and GT Rich Oligonucleotides on Microchip and
      in Solution.
AB  - Abstract   Formation of triple helices with GA and GT third strands has been
      studied. Besides the usual investigation techniques common for characterizing
      triple helical formation (CD spectroscopy, gel shift mobility assay, chemical
      probing and S1 nuclease footprinting) we have used a new technique in which
      targeting of polypurine sequences in duplexes was demonstrated on oligonucleotide
      microchips. This technique is very successful to quickly test a large number of
      potential triple helix formation. In this work we used oligonucleotide microairay
      to study the specificity of DNA duplex recognition by GA and GT strands. Generic
      6-mer microchip containing all possible 4(6) = 4,096 single-stranded
      hexadeoxyribonucleotides immobilized within individual gel pads was applied. To
      study formation of intermolecular triple helices on the generic microchip, a
      number of Pu.Py duplexes were formed by hybridization of the mixture of purine
      octadeoxyribonucleotides on the microchip followed by targeting of the duplexes
      by GA or GT third strands. Melting behavior of the formed structures was
      investigated using fluorescence measurements under microscope. In solution we
      present the results obtained for GT triplexes and discuss the characteristics of
      the CD spectra. Results obtained by S1 nuclease footprinting, KMnO(4) and DMS
      chemical probing are consistent with the spectroscopic data reflecting triplex
      structure formation.

PMID- 22607430
TI  - NMR Structural Studies on a DNA Four-Way Junction: Stacking Preference and
      Localization of the Metal-ion Binding Site.
AB  - Abstract   The stacking preference of a DNA Four-Way junction (4H), with a novel
      junction sequence, has been determined in the presence of magnesium ions as well
      as in the presence of cobalt(III)hexammine ions by means of NMR spectroscopy. In
      both cases this 4H has a strong preference (>80%) to fold in an A/D-stacked
      conformer. NOESY spectra showed intermolecular NOE contacts between 4H protons
      and the ammine protons of the cobalt(III)hexammine complex. These contacts define
      the metal-ion binding site, located in the vicinity of the junction. The position
      is similar to the observed site in a recent X-ray structure of a RNA/DNA hybrid
      4H and consistent with the position deduced from an uranyl ion photoprobing study
      on 4Hs with different sequences.

PMID- 22607431
TI  - Intramolecular i-Motif Structures of Telomeric DNA.
AB  - Abstract   The i-motif is an intercalated structure formed by association in a
      head to tail orientation of two parallel duplexes whose strands are held together
      by hemiprotonated C.C(+) pairs. The i-motif may be formed by a single strand
      containing four cytidine repeats, by association of two strands containing two
      cytidine repeats or by four strands containing a single cytidine stretch. The
      repeated C-rich sequences of centromeric and telomeric regions can potentially
      fold into an intramolecular i-motif.   We have investigated by NMR spectroscopy
      the structure of d(CCCTA(2)CCCTA(2)CCCTA(2)CCCT), a fragment of the vertebrate
      telomere. It includes an i-motif core of six intercalated C.C(+) pairs. At one
      end (the "top"), the central TA(2) linker loops across one of the narrow grooves,
      and the core is extended by base stacking in the loop. At the bottom, where the
      two other TA(2) linkers loop across the wide grooves, the NMR spectra reveal
      motions in the microsecond to millisecond scale. The pseudo-symmetry of the
      structure, which results in degenerate spectra and poor resolution, was broken by
      appropriate substitution of T by U and of C by 5-methylcytidine (5mC). This
      allowed us to solve the structure of d(CCCTA(2)5mCCCTA(2)CCCUA(2)CCCT). The
      motion is restricted to a flip of A18 around the glycosidic bond. Returning to
      the pseudo-symmetrical sequence, we find that each of the bottom loops switches
      between the structures of the first and third loops of the non-symmetrical
      sequence.   We also analyzed the effects of the loop sequence and of the length
      of the C-stretches on the topology and stability of the intramolecular i-motif
      structure.

PMID- 22607432
TI  - Two dimensions and two States in DNA nanotechnology.
AB  - Abstract   The construction of periodic matter and nanomechanical devices are
      central goals of DNA nanotechnology. The minimal requirements for components of
      designed crystals are [1] programmable interactions, [2] predictable local
      intermolecular structures and [3] rigidity. The sticky-ended association of DNA
      molecules fulfills the first two criteria, because it is specific and diverse,
      and it results in the formation of B-DNA. Stable branched DNA molecules permit
      the formation of networks, but individual single branches are too flexible.
      Antiparallel DNA double crossover (DX) molecules can provide the necessary
      rigidity, so we use these components to tile the plane. It is possible to include
      DNA hairpins that act as topographic labels for this 2-D crystalline array,
      because they protrude from its plane. By altering sticky ends, it is possible to
      change the topographic features formed by these hairpins, and to detect these
      changes by means of AFM. We can modify arrays by restricting hairpins or by
      adding them to sticking ends protruding from the array.   Although individual
      branched junctions are unsuitable for use as crystalline components,
      parallelograms of four 4-arm junction molecules are sufficiently rigid that they
      can be used to produce 2D arrays. The arrays contain cavities whose dimensions
      are readily tuned by changing the edges of their parallelogram components. We
      have used these arrays to measure directly the angle between the helices of the
      Holliday junction.   The rigidity of the DX motif can also be exploited to
      produce a nanomechanical device predicated on the B-Z transition. Two DNA double
      crossover molecules have been joined by a segment of DNAcapable of undergoing the
      B-Z transition. In the B-conformation, the unconnected helices of the two
      molecules are on the same side of the connecting helix, whereas in the Z
      conformation they are on opposite sides, leading to movements of as much as 60A.
      This effect is shown by fluorescence resonance energy transfer, because dyes
      attached to the unconnected helices have different separations in the two states.

PMID- 22607433
TI  - Algorithmic Self-Assembly of DNA: Theoretical Motivations and 2D Assembly
      Experiments.
AB  - Abstract   Biology makes things far smaller and more complex than anything
      produced by human engineering. The biotechnology revolution has for the first
      time given us the tools necessary to consider engineering on the molecular level.
      Research in DNA computation, launched by Len Adleman, has opened the door for
      experimental study of programmable biochemical reactions. Here we focus on a
      single biochemical mechanism, the self-assembly of DNA structures, that is
      theoretically sufficient for Turing-universal computation. The theory combines
      Hao Wang's purely mathematical Tiling Problem with the branched DNA constructions
      of Ned Seeman. In the context of mathematical logic, Wang showed how jigsaw
      shaped tiles can be designed to simulate the operation of any Turing Machine. For
      a biochemical implementation, we will need molecular Wang tiles. DNA molecular
      structures and intermolecular interactions are particularly amenable to design
      and are sufficient for the creation of complex molecular objects. The structure
      of individual molecules can be designed by maximizing desired and minimizing
      undesired Watson-Crick complementarity. Intermolecular interactions are
      programmed by the design of sticky ends that determine which molecules associate,
      and how. The theory has been demonstrated experimentally using a system of
      synthetic DNA double-crossover molecules that self-assemble into two-dimensional
      crystals that have been visualized by atomic force microscopy. This experimental
      system provides an excellent platform for exploring the relationship between
      computation and molecular self-assembly, and thus represents a first step toward
      the ability to program molecular reactions and molecular structures.

PMID- 22607434
TI  - Recent highlights from atomic force microscopy of DNA.
AB  - Abstract   Seven recent highlights are presented from atomic force microscopy
      (AFM) of DNA in this lab. The first two involve advances in the observation of
      enzymatic reactions in near-physiological solutions. E. coli RNA polymerase was
      observed to process along its DNA template in a series of time-lapse images [S.
      Kasas, et al., Biochemistry 36, 461 (1997)], and a new small-cantilever atomic
      force microscope (AFM) imaged DNA degradation by DNase I at rates as fast as two
      seconds per image. The next five highlights involve structural observations of
      DNA and DNA-protein complexes, including DNA condensed for gene delivery,
      sequence-dependent DNA condensation, an AFM assay for RNA polymerase, and AFM
      evidence for a yeast kinetochore complex that may be involved in holding together
      sister chromatids during cell division.

PMID- 22607435
TI  - Probing DNA conductivity with photoinduced electron transfer and scanning
      tunneling microscopy.
AB  - Abstract   The possibility that the stacked DNA bases can mediate vectorial
      electron transfer has been examined using two different approaches. Experiments
      on photoinduced electron transfer with intercalated donors and acceptors (either
      randomly bound or linked dyads of ruthenium complex and viologen) indicate that
      while DNA may be a better medium than acetonitrile for electron transfer over
      short distances (2-3-base pair, equivalent to 10-14A centre-to-centre
      separation), it is a poor medium for transport over larger separations. Attempts
      to measure conductivity of individual DNA molecules using scanning tunneling
      microscopy to image mixed monolayers of mercaptohexanol (MCH) and 30-mer or 10
      mer DNAs with alkanethiol linkers also indicate that DNA in its native state is a
      poor conductor. AFM images of the DNA/MCH mixed monolayers show that the DNA
      molecules extend vertically upward from the surface in such surface
      architectures.

PMID- 22607437
TI  - Long-range hole transport in DNA.
AB  - Abstract   A guanine radical cation (G(+*)) was site-selectively generated in
      double-stranded DNA and the hole transport from G(+*) to a GGG unit in
      G(+*)(TTG)(N)GG sites (N=1-4) was analyzed. The overall rate of the charge
      transfer exhibits a weak (algebraic) distance dependence, i. e. k ? N (eta) with
      eta = 1.7+/-0.2. This result supports that long-range hole migration in mixed DNA
      strands is a multistep hopping process between G bases.

PMID- 22607436
TI  - DNA-Mediated Electron Transfer: A Sensitive Probe of DNA-Protein Interactions.
AB  - Abstract   The ability of the pi-stacked array of heterocyclic DNA bases to
      behave as an efficient conduit for charge migration has been explored using a
      wide array of experimental approaches. Spectroscopic studies and biochemical
      assays show that charge transfer through well-stacked DNA can be extremely
      facile, although sensitive to structural distortions within the DNA base stack.
      The efficiency of these long-range reactions depends upon the coupling of the
      electron donor, acceptor and intervening base pairs within the base stack. As a
      result, base mismatches and stacking disruptions associated with protein binding
      to the helix can significantly perturb long range charge transfer. DNA-protein
      interactions which result in the base flipping of a nucleotide out of the DNA pi
      stack, in particular, dramatically inhibit long-range charge transfer through
      DNA. Whether these reactions that can occur over large molecular distances, be
      applied in sensing DNA damage, and be modulated by DNA-binding proteins, are
      exploited within the cell remains to be determined.

PMID- 22607438
TI  - M-DNA: pH Stability, Nuclease Resistance and Signal Transmission.
AB  - Abstract   In the presence of divalent metal ions (Zn(2)+, Co(2)+, and Ni(2)+)
      and at pHs above 8, duplex DNA forms a complex called M-DNA. M-DNA can be
      converted back to B-DNA by addition of EDTA or lowering the pH. The stability of
      M-DNA depends on the metal ion and/or the sequence of DNA. For calf thymus DNA
      the order of stability with decreasing pH is: Ni(2+)> Co(2+)>Zn(2++). The
      interconversion with B-DNA shows hysteresis; once formed Ni-M- DNA remains stable
      for more than one hour at pH 7, but conversion of B-DNA to M-DNA is slow at pHs
      below 8. Among synthetic sequences, poly[d(AT)] does not form M-DNA whereas the
      phosphorothioate analogues form only at pH 9.0. In contrast, the Ni-M-DNA form of
      poly[d(GC)] is stable even at pH 6.5. Ni-M-DNA is resistant to cleavage by DNase
      I whereas B-DNA is digested rapidly under identical conditions. The Co(2)+ and
      Ni(2+) forms of M-DNA were paramagnetic with increased mass susceptibilities
      (chi) compared to other metal complexes. Signal transmission in M-DNA was tested
      by constructing duplexes of 54 base pairs with fluorescein (donor) at one end and
      rhodamine (acceptor) at the other. Quenching of fluorescein fluorescence was
      observed for the Zn(2+) form of M-DNA only when the DNA was labeled with both
      donor and acceptor. Therefore, the pathway of quenching maybe via electron
      transfer. Taken together, these results suggest that M-DNA is a distinct
      conformation with tightly bound metal ions, and certain forms may be stable under
      physiological conditions. Furthermore, M-DNA may be used as a molecular wire for
      signal transmission over long distances.

PMID- 22607439
TI  - NMR studies of DNA structures containing sheared purine*purine and
      purine*pyrimidine base pairs.
AB  - Summary   Sheared purine*purine or purine*pyrimidine base pairs are important
      motifs in nucleic acid structures. They can exist either as tandem base pairs or
      as a single base pair closing hairpin mini-loops. Presence of such stable motifs
      greatly increases the structural repertoire of nucleic acid molecules and may
      play important roles in the contemporary nucleic acid studies. Several RNA
      crystal structures containing adjacent cross-strand base stacking have been
      solved. In this review, I will discuss the NMR studies and structural features
      for DNA molecules containing sheared G*A, A*A, or A*C base pairs. Special
      attention will be focused on exchangeable proton data, which have turned out to
      be crucial to the determination of unusual nucleic acid structures. The special
      features of the partial HIV-1 RT 21-mer act as a good example for correlating the
      (31)P chemical shifts to the zeta and alpha torsional angles of the backbone
      phosphate diesters.

PMID- 22607440
TI  - DNA bending and sugar switching.
AB  - Abstract   Using high frequency antiphase NMR spectroscopy and computer
      simulations of the antiphase spectra, we studied the equlibria in the sugar
      conformations in the DNA duplex 11-mer containing the AAA tract surrounded by
      cytosines. We demonstrate that at the 3'-end of the A-tract, the sugar switches
      from the common S-conformer (B-like form) to the N-conformer (A-like form) with
      the probability of 50-60%, thus creating a purine-pyrimidine step with
      heteronomous characteristics. The presence of this local B-A junction in one
      strand leads to compression of the interphosphate distance in this strand. We
      calculate the effect of this sugar switch on the helical parameters that are
      related to DNA bending. Finally, we suggest that the heteronomous deformation
      present in the A(n)C motif of unbound DNA duplexes might be the initial
      recognition site for proteins which bind to such junctions; and that in A(n)C
      stretches, DNA bending is a complicated dynamic process, i.e., locally
      noncanonical N conformers of the sugar phosphate backbone mix in with the B-like
      S conformers leading to bending.

PMID- 22607441
TI  - Nucleic Acid Structure Investigated by UV Resonance Raman Spectroscopy:
      Protonation Effects and A-Tract Structure.
AB  - Abstract   UV resonance Raman (UVRR) spectroscopy has been used to investigate
      the three purine bases, adenine, guanine and inosine, as a function of pH.
      Excitation wavelengths of 260 and 210 nm were used to probe the in-plane ring
      stretching frequencies and the exocyclic functional groups, respectively. These
      studies are suggestive that tautomeric forms can be stabilized at low and high pH
      values and these forms can be identified using UVRR spectroscopy. At pH values
      <=5.0, a band at 1693 cm (-1) is observed in the UVRR spectra of dAMP, which is
      suggestive of the imino protonated tautomer. At pH values of 10.0 and above both
      dGMP and IMP show evidence for forming the enolate tautomer, by the loss in
      intensity of the C=O stretching mode at 1686 cm(-1). The protonated forms of dGMP
      and dAMP exhibit distinct Raman bands at approximately 1460 and 1561 cm(-1) and
      we suggest that these protonated states can be identified using UVRR
      spectroscopy. Most distinctively, the -NH(2) scissors mode of dGMP and dAMP
      shifts up in frequency and increases in intensity as the pH is decreased.
      Interestingly, these features are also observed in a comparison of an A-tract
      containing dodecamer with a non A-tract dodecamer. In particular, a frequency
      upshift of the -NH(2) scissors mode and a mode at 1466 cm(-1) is observed.
      Because of the resonance enhancement and the similarities to the protonated dAMP
      spectrum, these features are attributed to the dA residues in the A-tract. It is
      suggested that these spectral features may be characteristic of 'bent' DNA.

PMID- 22607442
TI  - Drug Self-Assembly on DNA: Sequence Effects with trans-bis-(4-N
      methylpyridiniumyl)diphenyl Porphyrin and Hoechst 33258.
AB  - Abstract   Self assembly in biological systems is increasingly being recognised
      as an important phenomenon. We have examined two model systems: the cationic meso
      substituted free base porphyrin derivative frans-bis-(4-N
      methylpyridiniumyl)diphenyl porphyrin (t-H(2)P) and Hoechst 33258 (Hoechst) both
      of which were known to assemble on DNA. t-H(2)P self-assembles in solution under
      appropriate conditions, whereas Hoechst does not. By varying ionic strength and
      ligand: DNA mixing ratios, these features together with their different steric
      constraints have led to quite different DNA binding behaviour. Hoechst on
      poly[d(A-T)](2) stacks across the major groove, probably after filling its well
      established monomeric minor groove binding mode. By way of contrast the
      Hoechst/poly[d(G-C)](2) self-assembled aggregates involve partially intercalated
      molecules stacking in the major groove. The binding mode adopted by t-H(2)P with
      poly[d(A-T)](2) and poly[d(G-C)](2) appears to be kinetically controlled and to
      be determined by the pre-existence of monomer binding and/or ligand stacks in
      solution. With poly[d(A-T)](2) the modes adopted both involve displacing the DNA
      bases to be more parallel than perpendicular to the helix axis. One is probably
      based on porphyrin intercalation and the other on minor groove binding. Resonance
      light scattering, linear dichroism, circular dichroism, normal absorption and
      fluorescence spectroscopies have been used to characterise the self-assembly in
      these systems.

PMID- 22607443
TI  - Stabilization of Double Stranded Homologous Poly(dA).Poly(dT) by Taxol.
AB  - Abstract   The nucleic acid activity of taxol and paclitaxel was investigated
      with synthetic and natural oligo- and polynucleotides. The polynucleotides
      poly(dA).poly(dT), poly(dG).poly(dC), poly [d(A-T)].poly[d(A-T)], poly[d(G
      C)].poly[d(G-C)] and calf thymus DNA were used. The oligonucleotides are 24-mers
      with d(purine)(24).d(pyrimidine)(24) strands, as well as d[(purine)(x)
      (pyrimidine)(x)].d[(purine)(x)-(pyrimidine)(x)] sequences. The study was
      performed with spectroscopic and calorimetric methods in dilute and condensed DNA
      solutions.   In a recent study, taxol and paclitaxel showed molecular recognition
      of AT nucleotides with a high affinity to homologous (dA).(dT) sequences; no
      interaction with GC nucleotides could be observed. An astonishing stabilization
      of the DNA duplex up to DeltaT(m) = 25 degrees C was measured by thermal
      denaturation with poly(dA).poly(dT)/paclitaxel complexes. Circular dichroism
      signals of DNA (24-mer) containing homologous (dA).(dT) tracts increased with
      increasing amount of the drug; for the other oligo- and polynucleotides no change
      in the spectra could be found. Contrary to this findings, circular dichroism (CD)
      spectra of poly(dA).poly(dT)/paclitaxel complexes displayed reduced intensities
      of the signals at increasing drug concentrations.   These findings in dilute
      solutions were complemented by differential scanning calorimetric investigations
      in condensed states (only calf thymus DNA tested). Increasing enthalpies by
      increasing amount of the drug point to a stabilization.   Simple phosphate
      backbone interaction in the narrow groove of (dA).(dT) tracts could be a
      sufficient explanation for all the results. Hydrophilic side groups of the drug
      interact with the phosphate and clip the strands together, while the hydrophobic
      parts of the molecule may disturb the polynucleobase formation.

PMID- 22607444
TI  - DNA Sequence Recognition of a Cross-Linked Polyamide: CD Studies, Footprinting
      and Effects on the Activity of DNA Gyrase.
AB  - Abstract   Using circular dichroism the binding ability of a cross-linked
      thiazole-lexitropsin, composed of two polyamide strands (with the base binding
      residues thiazole-imidazole-pyrrole) to a series of dodecamer duplexes containing
      different central sequences, has been examined. The binding of the dimer with a
      heptanediyl linker (C7 dimer) was compared with that of the lexitropsin monomer
      at 200 mM NaCl and 2 M NaCl. The C7 dimer exhibits a clear-cut different binding
      tendency to various dodecamers at 2 M NaCl indicating that sequence specificity
      becomes apparent at high salt concentration. The highest binding preference
      occurs to the dodecamers with the central sequences: AACGTT, AAGTTT and ATCGTA
      but almost no affinity was observed at 2 M NaCl for AGCGCT, ATCGAT and AAATTT.
      From the results it appears that the sequence selectivity of the dimer can be
      ascribed to the side-by-side binding mode of the cross-linked polyamide strands
      in the minor groove. In contrast no similar variation was found in the binding
      behavior for the lexitropsin monomer. Modification of the leading residue on the
      thiazoles of the dimer significantly lowers (or even abolishs) the binding
      ability, e.g. if the amino group is replaced by formyl or an acetyl residue.
      Footprinting and melting temperature data are in agreement with the CD results.
      Comparative in vitro studies on the influence of the lexitropsins on DNA gyrase
      demonstrate that the dimer has a higher inhibitory potency on the enzymatic
      activity compared to the monomer in accord with the observed DNA binding
      differences. A scheme of a possible side- by-side alignment of the C7 dimer in
      the minor groove is proposed.

PMID- 22607445
TI  - Pf1 filamentous phage as an alignment tool for generating local and global
      structural information in nucleic acids.
AB  - Abstract   Pf1 filamentous phage represent a simple versatile method for
      generating partially ordered macromolecules in solution. The phage allow tunable
      degrees of alignment of macromolecules under a wide range of temperature and
      solvent conditions. The negatively charged phage are ideal for aligning
      negatively charged nucleic acids and these phage-nucleic acid solutions are
      stable indefinitely. We have used Pf1 phage to align various DNA and RNA
      molecules in solution for measurement of dipolar coupling interactions. These
      dipolar couplings can be used to improve the local structure of nucleic acids.
      More importantly they also contain information on the global structure, such as
      DNA bending, which presently cannot be obtained by standard NMR methods. The
      principles involved in using Pf1 phage to generate solutions of partially order
      macromolecules will be discussed. The use of (1)H-(1)H, (1)H-(13)C and (1)H-(15)N
      dipolar couplings for generating angle constraints for structure refinement of
      nucleic acids will also be discussed.

PMID- 22607446
TI  - Anomalous Migration of Short Sequences of DNA: Comparison of Theory and
      Experiment.
AB  - Abstract   A new model to replace the Ogstron and tube reptation models for gel
      retardation of DNA is proposed that explicitly takes into account screening of
      the hydrodynamic interactions and polyelectrolyte effects. At short DNA sequence
      lengths, significant anomalous migration is predicted whose onset is dependent on
      the size of polyacrylamide gel pores. Thus, a 2-residue fragment has the same
      electrophoretic mobility as a 12-residue fragment for a polyacrylamide gel with a
      mesh size of 60A. The oligonucleotide length at which anomalous migration is
      observed also depends on pore size. Experimental measurement of gel mobility for
      DNA fragments of the form N(pN)(n), where n = 1-11, 14 and 19 substantiate this
      phenomenon.

PMID- 22607447
TI  - Evaluation of inadequate, indeterminate, false-negative and false-positive cases
      in cytological examination for breast cancer according to histological type.
AB  - BACKGROUND: We previously investigated the current status of breast cytology
      cancer screening at seven institutes in our area of southern Fukuoka Prefecture,
      and found some differences in diagnostic accuracy among the institutions. In the
      present study, we evaluated the cases involved and noted possible reasons for
      their original cytological classification as inadequate, indeterminate, false
      negative and false-positive according to histological type. METHODS: We evaluated
      the histological findings in 5693 individuals who underwent cytological
      examination for breast cancer (including inadequate, indeterminate, false
      negative and false-positive cases), to determine the most common histological
      types and/or features in these settings and the usefulness/limitations of
      cytological examination for the diagnosis of breast cancer. RESULTS: Among 1152
      cytologically inadequate cases, histology revealed that 75/173 (43.6%) cases were
      benign, including mastopathy (fibrocystic disease) in 38.6%, fibroadenoma in
      24.0% and papilloma in 5.3%. Ninety-five of 173 (54.9%) cases were histologically
      malignant, with scirrhous growing type, invasive ductal carcinoma (SIDC) being
      significantly more frequent (49.5%) than papillotubular growing type (Papi-tub)
      (P < 0.0001), solid-tubular growing type (P = 0.0001) and ductal carcinoma in
      situ (DCIS) (P = 0.0001). Among 458 indeterminate cases, 54/139 (38.8%) were
      histologically benign (mastopathy, 30.0%; fibroadenoma, 27.8%; papilloma, 26.0%)
      and 73/139 (52.5%) were malignant, with SIDC being the most frequent malignant
      tumor (37.0%). Among 52 false-negative cases, SIDC was significantly more
      frequent (42.3%) than DCIS (P = 0.0049) and Papi-tub (P = 0.001). There were
      three false-positive cases, with one each of fibroadenoma, epidermal cyst and
      papilloma. CONCLUSIONS: The inadequate, indeterminate, false-negative and false
      positive cases showed similar histological types, notably SIDC for malignant
      tumors, and mastopathy, fibroadenoma and papilloma for benign cases. We need to
      pay particular attention to the collection and assessment of aspirates for these
      histological types of breast disease. In particular, several inadequate,
      indeterminate and false-negative cases with samples collected by aspiration were
      diagnosed as SIDC. These findings should encourage the use of needle biopsy
      rather than aspiration when this histological type is identified on imaging.
      Namely, good communication between clinicians and pathological staff, and triple
      assessment (i.e., clinical, pathological and radiological assessment), are
      important for accurate diagnosis of aspiration samples. VIRTUAL SLIDES: The
      virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/7349809170055423.

PMID- 22607448
TI  - Amino acid bound surfactants: a new synthetic family of polymeric monoliths
      opening up possibilities for chiral separations in capillary
      electrochromatography.
AB  - By combining a novel chiral amino-acid surfactant containing an acryloyl amide
      tail, a carbamate linker, and a leucine headgroup of different chain lengths with
      a conventional cross-linker and a polymerization technique, a new "one-pot"
      synthesis for the generation of amino-acid based polymeric monolith is realized.
      The method promises to open up the discovery of an amino-acid based polymeric
      monolith for chiral separations in capillary electrochromatography (CEC). The
      possibility of enhanced chemoselectivity for simultaneous separation of ephedrine
      and pseudoephedrine containing multiple chiral centers and the potential use of
      this amino-acid surfactant bound column for CEC and CEC coupled to mass
      spectrometric detection are demonstrated.

PMID- 22607449
TI  - HiTSEE KNIME: a visualization tool for hit selection and analysis in high
      throughput screening experiments for the KNIME platform.
AB  - We present HiTSEE (High-Throughput Screening Exploration Environment), a
      visualization tool for the analysis of large chemical screens used to examine
      biochemical processes. The tool supports the investigation of structure-activity
      relationships (SAR analysis) and, through a flexible interaction mechanism, the
      navigation of large chemical spaces. Our approach is based on the projection of
      one or a few molecules of interest and the expansion around their neighborhood
      and allows for the exploration of large chemical libraries without the need to
      create an all encompassing overview of the whole library. We describe the
      requirements we collected during our collaboration with biologists and chemists,
      the design rationale behind the tool, and two case studies on different datasets.
      The described integration (HiTSEE KNIME) into the KNIME platform allows
      additional flexibility in adopting our approach to a wide range of different
      biochemical problems and enables other research groups to use HiTSEE.

PMID- 22607450
TI  - The cephalostatins. 22. synthesis of bis-steroidal pyrazine pyrones (1).
AB  - Cephalostatin 1 (1), a remarkably strong cancer cell growth inhibitory
      trisdecacyclic, bis-steroidal pyrazine isolated from the marine tube worm
      Cephalodiscus gilchristi, continues to be an important target for practical total
      syntheses and a model for the discovery of less complex structural modifications
      with promising antineoplastic activity. In the present study, the cephalostatin E
      and F rings were greatly simplified by replacement at C-17 with an alpha-pyrone
      (in 12), typical of the steroidal bufodienolides, and by a dihydro-gamma-pyrone
      (in 16). The synthesis of pyrazine 12 from 5alpha-dihydrotestosterone (nine
      steps, 8% overall yield) provided the first route to a bis-bufadienolide
      pyrazine. Dihydro-gamma-pyrone 16 was synthesized in eight steps from ketone 13.
      While only insignificant cancer cell growth inhibitory activity was found for
      pyrones 12 and 16, the results provided further support for the necessity of more
      closely approximating the natural D-F ring system of cephalostatin 1 in order to
      obtain potent antineoplastic activity.

PMID- 22607451
TI  - Hexavalent chromium disrupts mitosis by stabilizing microtubules in Lens
      culinaris root tip cells.
AB  - Hexavalent chromium [Cr(VI)] is an accumulating environmental pollutant due to
      anthropogenic activities, toxic for humans, animals and plants. Therefore, the
      effects of Cr(VI) on dividing root cells of lentil (Lens culinaris) were
      investigated by tubulin immunofluorescence and DNA staining. In Cr(VI)-treated
      roots, cell divisions were perturbed, the chromosomes formed irregular
      aggregations, multinucleate cells were produced and tubulin clusters were
      entrapped within the nuclei. All cell cycle-specific microtubule (MT) arrays were
      affected, indicating a stabilizing effect of Cr(VI) on the MTs of L. culinaris.
      Besides, a time- and concentration-dependent gradual increase of acetylated alpha
      tubulin, an indicator of MT stabilization, was observed in Cr(VI)-treated roots
      by both immunofluorescence and western blotting. Evidence is also provided that
      reactive oxygen species (ROS) caused by Cr(VI), determined with the specific
      marker dichlorofluorescein, may be responsible for MT stabilization. Combined
      treatments with Cr(VI) and oryzalin revealed that Cr(VI) overcomes the
      depolymerizing ability of oryzalin, as it does experimentally introduced hydrogen
      peroxide, further supporting its stabilizing effect. In conclusion, it is
      suggested that the mitotic aberrations caused by Cr(VI) in L. culinaris root
      cells may be the result of MT stabilization rather than depolymerization, which
      consequently disturbs MT dynamics and their related functions.

PMID- 22607452
TI  - Quantitative trait loci segregating in crosses between New Hampshire and White
      Leghorn chicken lines: III. Fat deposition and intramuscular fat content.
AB  - In this study, a genome scan was performed to detect genomic loci that affect fat
      deposition in white adipose tissues and muscles in 278 F (2) males of reciprocal
      crosses between the genetically and phenotypically extreme inbred chicken lines
      New Hampshire (NHI) and White Leghorn (WL77). Genome-wide highly significant
      quantitative trait loci (QTL) influencing fat deposition in white adipose tissues
      were found on GGA2 and 4. The peak QTL positions for different visceral and
      subcutaneous white adipose tissues were located between 41.4 and 112.4 Mb on GGA2
      and between 76.2 and 78.7 Mb on GGA4, which explained 4.2-10.4% and 4.3-11.6%
      respectively of the phenotypic F (2) variances. Contrary to our expectations, the
      QTL allele descending from the lean line WL77 on GGA4 led to increased fat
      deposition. We suggest a transgressive action of the obesity allele only if it is
      not in the genetic background of the line WL77. Additional highly significant
      loci for subcutaneous adipose tissue mass were identified on GGA12 and 15. For
      intramuscular fat content, a suggestive QTL was located on GGA14. The analysed
      crosses provide a valuable resource for further fine mapping of fatness genes and
      subsequent gene discovery.

PMID- 22607453
TI  - Sustained glycolytic oscillations in individual isolated yeast cells.
AB  - Yeast glycolytic oscillations have been studied since the 1950s in cell-free
      extracts and intact cells. For intact cells, sustained oscillations have so far
      only been observed at the population level, i.e. for synchronized cultures at
      high biomass concentrations. Using optical tweezers to position yeast cells in a
      microfluidic chamber, we were able to observe sustained oscillations in
      individual isolated cells. Using a detailed kinetic model for the cellular
      reactions, we simulated the heterogeneity in the response of the individual
      cells, assuming small differences in a single internal parameter. This is the
      first time that sustained limit-cycle oscillations have been demonstrated in
      isolated yeast cells. DATABASE: The mathematical model described here has been
      submitted to the JWS Online Cellular Systems Modelling Database and can be
      accessed at http://jjj.biochem.sun.ac.za/database/gustavsson/index.html free of
      charge.

PMID- 22607454
TI  - New grower-friendly methods for plant pathogen monitoring.
AB  - Accurate plant disease diagnoses and rapid detection and identification of plant
      pathogens are of utmost importance for controlling plant diseases and mitigating
      the economic losses they incur. Technological advances have increasingly
      simplified the tools available for the identification of pathogens to the extent
      that, in some cases, this can be done directly by growers and producers
      themselves. Commercially available immunoprinting kits and lateral flow devices
      (LFDs) for detection of selected plant pathogens are among the first tools of
      what can be considered grower-friendly pathogen monitoring methods. Research
      efforts, spurned on by point-of-care needs in the medical field, are paving the
      way for the further development of on-the-spot diagnostics and multiplex
      technologies in plant pathology. Grower-friendly methods need to be practical,
      robust, readily available, and cost-effective. Such methods are not restricted to
      on-the-spot testing but extend to laboratory services, which are sometimes more
      practicable for growers, extension agents, regulators, and other users of
      diagnostic tests.

PMID- 22607455
TI  - Survival analysis of mandibular complete dentures with acrylic-based resilient
      liners.
AB  - OBJECTIVE: The purpose of this long-term randomised controlled trial was to
      compare the longevity of dentures constructed using a conventional acrylic resin
      (CAR) to that of dentures constructed using an acrylic-based resilient liner
      (ARL). MATERIALS AND METHODS: The follow-up study was essentially carried out by
      annual telephone calls to each of the 67 participants. The Kaplan-Meier method
      and life-table analysis were used for univariate analyses. The Cox proportional
      hazards test was used as a final model for statistically adjusting predictor
      variables such as sex, clinician type, mandibular denture type and age at denture
      delivery. RESULTS: The denture type was likely to affect the survival time of the
      dentures, while the sex and clinician type were not. The group using acrylic
      based resilient denture liners had twice the risk of having shorter denture
      survival times than those using conventional acrylic resin dentures. Younger
      participants were likely to have a reduced risk of having shorter denture
      survival times than older participants. CONCLUSION: We conclude that mandibular
      complete dentures constructed using ARL are twice as likely as dentures
      constructed using CAR to have shorter denture survival times, mainly because of
      material deterioration.

PMID- 22607456
TI  - Identification of positive and negative regulators of disease resistance to rice
      blast fungus using constitutive gene expression patterns.
AB  - Elevated constitutive expression of components of the defence arsenal is
      associated with quantitative resistance to the rice blast fungus, a phenomenon
      called preformed defence. While the role of many disease regulators in inducible
      defence systems has been extensively studied, little attention has been paid so
      far to genes that regulate preformed defence. In this study, we show by
      microarray analysis across rice diversity that the preformed defence phenomenon
      impacts on a large number of defence-related genes without apparently affecting
      other biological processes. Using a guilt-by-association strategy, we identified
      two positive regulators that promote constitutive expression of known defence
      markers and partial resistance to rice blast. The HSF23 gene encodes for a
      putative member of the heat shock transcription factor family, while CaMBP
      encodes for a putative Calmodulin-binding protein. Both HSF23 and CaMBP strongly
      affect preformed defence and also plant growth. Additionally, we identified the
      OB-fold gene as a negative regulator of blast resistance, which could be involved
      in RNA stabilization. The OB-fold mutants do not suffer from obvious
      developmental defects. Taken together, our results prove that our strategy of
      combining analysis of gene expression diversity with guilt-by-association is a
      powerful way to identify disease resistance regulators in rice.

PMID- 22607457
TI  - Hierarchical three-dimensional ZnCo2O4 nanowire arrays/carbon cloth anodes for a
      novel class of high-performance flexible lithium-ion batteries.
AB  - Flexible electronics is an emerging and promising technology for next generation
      of optoelectronic devices. Herein, hierarchical three-dimensional ZnCo(2)O(4)
      nanowire arrays/carbon cloth composites were synthesized as high performance
      binder-free anodes for Li-ion battery with the features of high reversible
      capacity of 1300-1400 mAh g(-1) and excellent cycling ability even after 160
      cycles with a capacity of 1200 mAh g(-1). Highly flexible full batteries were
      also fabricated, exhibiting high flexibility, excellent electrical stability, and
      superior electrochemical performances.

PMID- 22607458
TI  - Drug discovery for a new generation of covalent drugs.
AB  - INTRODUCTION: The design of target-specific covalent inhibitors is conceptually
      attractive because of increased biochemical efficiency through covalency and
      increased duration of action that outlasts the pharmacokinetics of the agent.
      Although many covalent inhibitors have been approved or are in advanced clinical
      trials to treat indications such as cancer and hepatitis C, there is a general
      tendency to avoid them as drug candidates because of concerns regarding immune
      mediated toxicity that can arise from indiscriminate reactivity with off-target
      proteins. AREAS COVERED: The review examines potential reason(s) for the
      excellent safety record of marketed covalent agents and advanced clinical
      candidates for emerging therapeutic targets. A significant emphasis is placed on
      proteomic techniques and chemical/biochemical reactivity assays that aim to
      provide a systematic rank ordering of pharmacologic selectivity relative to off
      target protein reactivity of covalent inhibitors. EXPERT OPINION: While tactics
      to examine selective covalent modification of the pharmacologic target are
      broadly applicable in drug discovery, it is unclear whether the output from such
      studies can prospectively predict idiosyncratic immune-mediated drug toxicity.
      Opinions regarding an acceptable threshold of protein reactivity/body burden for
      a toxic electrophile and a non-toxic electrophilic covalent drug have not been
      defined. Increasing confidence in proteomic and chemical/biochemical reactivity
      screens will require a retrospective side-by-side profiling of marketed covalent
      drugs and electrophiles known to cause deleterious toxic effects via non
      selective covalent binding.

PMID- 22607459
TI  - Assessing health status in COPD. A head-to-head comparison between the COPD
      assessment test (CAT) and the clinical COPD questionnaire (CCQ).
AB  - BACKGROUND: Health status provides valuable information, complementary to
      spirometry and improvement of health status has become an important treatment
      goal in COPD management. We compared the usefulness and validity of the COPD
      Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ), two simple
      questionnaires, in comparison with the St. George Respiratory Questionnaire
      (SGRQ). METHODS: We administered the CAT, CCQ and SGRQ in patients with COPD
      stage I-IV during three visits. Spirometry, 6 MWT, MRC scale, BODE index, and
      patients perspectives on questionnaires were recorded in all visits. Standard
      Error of Measurement (SEM) was used to calculate the Minimal Clinical Important
      Difference (MCID) of all questionnaires. RESULTS: We enrolled 90 COPD patients.
      Cronbach's alpha for both CAT and CCQ was high (0.86 and 0.89, respectively).
      Patients with severe COPD reported worse health status compared to milder
      subgroups. CAT and CCQ correlated significantly (rho =0.64, p < 0.01) and both
      with the SGRQ (rho = 0.65; CAT and rho = 0.77; CCQ, p < 0.01). Both
      questionnaires exhibited a weak correlation with lung function (rho = -0.35;CAT
      and rho = -0.41; CCQ, p < 0.01). Their reproducibility was high; CAT: ICC = 0.94
      (CI 0.92-0.96), total CCQ ICC = 0.95 (0.92-0.96) and SGRQ = 0.97 (CI 0.95-0.98).
      The MCID calculated using the SEM method showed results similar to previous
      studies of 3.76 for the CAT, 0.41 for the CCQ and 4.84 for SGRQ. Patients
      suggested both CAT and CCQ as easier tools than SGRQ in terms of complexity and
      time considerations. More than half of patients preferred CCQ instead of CAT.
      CONCLUSIONS: The CAT and CCQ have similar psychometric properties with a slight
      advantage for CCQ based mainly on patients' preference and are both valid and
      reliable questionnaires to assess health status in COPD patients.

PMID- 22607461
TI  - Children's understanding of family financial resources and their impact on eating
      healthily.
AB  - Socioeconomic inequalities in childhood are linked to childhood and adult health
      inequalities. They are particularly closely associated with inequalities in
      nutritional and consequently health status. Recent research links this to the
      high cost of nutrient-rich and low cost of nutrient-poor foods and explores how
      parents negotiate food purchase on a limited budget. However, we know little of
      children's perspectives on the material and social realities of their lives and
      their involvement in health-relevant behaviour. This contrasts with a growing
      body of research which emphasises children's active role in making sense of and
      participating in health practices while growing up and their potential to act in
      continuity with and as agents of change in family health cultures. This paper
      explores children's understanding of family finances and how they perceive this
      to relate to eating healthily. It draws upon data from a qualitative study of 53
      children aged 9-10 from two socioeconomically contrasting schools in the North of
      England during 2010 and 2011. Data were generated in friendship group interviews
      and debates at school and individual interviews in the home, and analysed
      thematically. Children incorporated a variety of media information into their
      understandings and sought explanations from their personal experience. They had
      sophisticated ideas about the interrelationships between diet, cost and health
      and were acutely aware of how family finances influenced food purchase. Children
      proposed different strategies to facilitate eating healthily on a budget, but
      prioritised state and corporate responsibility in ensuring that eating healthily
      is affordable. This contrasts with current health-related policy, which does not
      address cost as a potential barrier to eating healthily in the home. Children
      also consistently conflated healthy eating with eating fruit and vegetables,
      highlighting a need to reinforce other important nutritional messages.

PMID- 22607462
TI  - Pool boiling of nanoparticle-modified surface with interlaced wettability.
AB  - This study investigated the pool boiling heat transfer under heating surfaces
      with various interlaced wettability. Nano-silica particles were used as the
      coating element to vary the interlaced wettability of the surface. The
      experimental results revealed that when the wettability of a surface is uniform,
      the critical heat flux increases with the more wettable surface; however, when
      the wettability of a surface is modified interlacedly, regardless of whether the
      modified region becomes more hydrophilic or hydrophobic, the critical heat flux
      is consistently higher than that of the isotropic surface. In addition, this
      study observed that critical heat flux was higher when the contact angle
      difference between the plain surface and the modified region was smaller.

PMID- 22607460
TI  - Engineering muscle tissues on microstructured polyelectrolyte multilayer films.
AB  - The use of surface coating on biomaterials can render the original substratum
      with new functionalities that can improve the chemical, physical, and mechanical
      properties as well as enhance cellular cues such as attachment, proliferation,
      and differentiation. In this work, we combined biocompatible polydimethylsiloxane
      (PDMS) with a biomimetic polyelectrolyte multilayer (PEM) film made of poly(L
      lysine) and hyaluronic acid (PLL/HA) for skeletal muscle tissue engineering. By
      microstructuring PDMS in grooves of a different width (5, 10, 30, and 100 MUm)
      and by modulating the stiffness of the (PLL/HA) films, we guided skeletal muscle
      cell differentiation into myotubes. We found optimal conditions for both the
      formation of parallel-oriented myotubes and their maturation. Significantly, the
      myoblasts were collectively prealigned to the grooves before their
      differentiation. Before fusion, the highest aspect ratio and orientation of
      nuclei were observed for the 5 and 10 MUm wide micropatterns. The formation of
      myotubes was observed regardless of the size of the micropatterns, and we found
      that their typical width was 10-12 MUm. Their maturation was characterized by the
      immunolabeling of type II isomyosin. The amount of myosin striation was not
      affected by the topography, except for the 5 MUm wide micropatterns. We
      highlighted the spatial constraints that led to an important nuclei deformation
      and further impairment of maturation within the 5 MUm grooves. Altogether, our
      results show that the PEM film combined with PDMS is a powerful tool that is used
      for skeletal muscle engineering. This work opens perspectives for the development
      of skeletal muscle tissue in contact with films containing bioactive peptides or
      growth factors as well as for the study of pathogenic myotubes.

PMID- 22607463
TI  - Ganciclovir ophthalmic gel 0.15%: safety and efficacy of a new treatment for
      herpes simplex keratitis.
AB  - BACKGROUND: Until the availability of ganciclovir ophthalmic gel in 2009, the
      only option for treating herpes simplex (HSV) keratitis in the USA has been
      trifluridine (TFT), a compound with tolerability issues related to its
      nonselective inhibition of DNA replication in both normal cells and virus
      infected cells. Ganciclovir has selective pharmacologic activity on viral
      thymidine kinase and a lower potential for toxicity to healthy human cells. Our
      objective was to evaluate safety and efficacy findings reported with the use of
      ganciclovir ophthalmic gel, both for HSV keratitis and other potential clinical
      indications. METHODS: Clinical and preclinical data with ganciclovir were
      identified through a comprehensive electronic search of PubMed and Medline, using
      the search terms ganciclovir, ganciclovir 0.15% ophthalmic gel, acyclovir,
      acyclovir ointment 3%, herpes simplex keratitis, treatment of herpes simplex
      keratitis, and adenoviral keratoconjunctivitis. The authors were also granted
      access to previously unpublished ganciclovir surveillance safety data from Bausch
      & Lomb, Inc. RESULTS: No clinical data comparing ganciclovir ophthalmic gel to 1%
      trifluorothymidine (TFT) for HSV keratitis could be identified. Four
      international, randomized, multicenter clinical trials have demonstrated that
      ganciclovir gel is at least as effective as acyclovir ointment for the treatment
      of HSV keratitis. Ganciclovir gel was better tolerated, with lower rates of
      blurred vision, eye irritation, and punctate keratitis. Recent data also indicate
      it may hold promise as a treatment for adenoviral keratoconjunctivitis. Worldwide
      safety surveillance data collected over the past 10-15 years in over 30 countries
      suggests an extremely low rate of spontaneously reported adverse events with
      ganciclovir ophthalmic gel. CONCLUSIONS: Current data suggest that ganciclovir
      ophthalmic gel has similar efficacy as acyclovir ointment for the treatment of
      HSV keratitis and is better tolerated. Clinical head-to-head studies comparing
      ganciclovir and TFT would be of great interest, especially for US physicians.

PMID- 22607464
TI  - The effect of in vitro digestion on steryl ferulates from rice (Oryza sativa L.)
      and other grains.
AB  - Polished and cargo rice, wild rice, rice bran, corn bran, and wheat bran were
      subjected to a static in vitro digestion model, to monitor changes in their
      steryl ferulate content and composition. Free sterols, possible hydrolysis
      products of steryl ferulates, were also measured. Additionally, steryl ferulate
      bioaccessibility was calculated as the percentage of steryl ferulates liberated
      from the grain matrix into the digestive juice. Steryl ferulate content ranged
      between 6.1 and 3900 MUg/g and decreased by 1-63% due to digestion. A parallel
      increase in free sterols of more than 70% was observed in all samples.
      Additionally, bioaccessibility of steryl ferulates was found to be almost
      negligible. These findings suggest that intestinal enzymes immediately hydrolyze
      steryl ferulates, which are liberated from the grain matrix, and thus they are
      practically unavailable for absorption in the small intestine. This further
      indicates that the hydrolysis products of steryl ferulates could be bioactive in
      the gut.

PMID- 22607465
TI  - Neopterin: a promising marker for the inflammation in polycystic ovary syndrome.
AB  - BACKGROUND: Several markers of low-grade chronic inflammation are altered in
      women with polycystic ovary syndrome (PCOS). Neopterin (NEO) is a marker of
      celullar immunity, and oxidative stress, mainly produced by activated
      macrophages. We aimed to evaluate the NEO levels in PCOS patients and correlate
      them with antropometric and biochemical parameters. METHODS: The study groups
      consisted of 69 women with PCOS and 46 healthy controls. Both groups were divided
      into two subgroups according to their body mass index (BMI): <25 = normoweight,
      >25 = overweight. The clinical and biochemical parameters and serum NEO levels
      were analyzed. RESULTS: Circulating levels of NEO were significantly (p < 0.001)
      higher in women with PCOS (normoweight: 15.9 +/- 4.7 nmol/l; overweight 13.3 +/-
      8.1 nmol/l) compared to controls (normoweight: 8.6 +/- 2.0 nmol/l; overweight 9.2
      +/- 1.8 nmol/l) regardless of their weight classes. Waist-to-hip ratio (WHR) (p <
      0.05), free and total testosterone (p < 0.001) were significantly elevated in
      women with PCOS compared to controls after controlling for the effect of obesity.
      CONCLUSION: Circulating NEO level s are elevated in PCOS independent of body mass
      index supporting the suggestion of PCOS is a low-grade chronic inflammatory
      state.

PMID- 22607466
TI  - Electromagnetic-induction logging to monitor changing chloride concentrations.
AB  - Water from the San Joaquin Delta, having chloride concentrations up to 3590 mg/L,
      has intruded fresh water aquifers underlying Stockton, California. Changes in
      chloride concentrations at depth within these aquifers were evaluated using
      sequential electromagnetic (EM) induction logs collected during 2004 through 2007
      at seven multiple-well sites as deep as 268 m. Sequential EM logging is useful
      for identifying changes in groundwater quality through polyvinyl chloride-cased
      wells in intervals not screened by wells. These unscreened intervals represent
      more than 90% of the aquifer at the sites studied. Sequential EM logging
      suggested degrading groundwater quality in numerous thin intervals, typically
      between 1 and 7 m in thickness, especially in the northern part of the study
      area. Some of these intervals were unscreened by wells, and would not have been
      identified by traditional groundwater sample collection. Sequential logging also
      identified intervals with improving water quality-possibly due to groundwater
      management practices that have limited pumping and promoted artificial recharge.
      EM resistivity was correlated with chloride concentrations in sampled wells and
      in water from core material. Natural gamma log data were used to account for the
      effect of aquifer lithology on EM resistivity. Results of this study show that a
      sequential EM logging is useful for identifying and monitoring the movement of
      high-chloride water, having lower salinities and chloride concentrations than sea
      water, in aquifer intervals not screened by wells, and that increases in chloride
      in water from wells in the area are consistent with high-chloride water
      originating from the San Joaquin Delta rather than from the underlying saline
      aquifer.

PMID- 22607468
TI  - Pyoderma gangrenosum in association with Janus kinase 2 (JAK2V617F) mutation.
AB  - Pyoderma gangrenosum (PG) commonly occurs in association with various
      haematological and inflammatory disorders. We report a new association, a Janus
      kinase (JAK)2 mutation, in a 63-year-old patient with PG. We hypothesise that PG
      occurs by direct activation of JAK along with signal transducers and activators
      of transcription (STAT), a common mechanism involved in the pathogenesis of
      inflammatory and haematological diseases.

PMID- 22607467
TI  - Optimal compressed sensing reconstructions of fMRI using 2D deterministic and
      stochastic sampling geometries.
AB  - BACKGROUND: Compressive sensing can provide a promising framework for
      accelerating fMRI image acquisition by allowing reconstructions from a limited
      number of frequency-domain samples. Unfortunately, the majority of compressive
      sensing studies are based on stochastic sampling geometries that cannot guarantee
      fast acquisitions that are needed for fMRI. The purpose of this study is to
      provide a comprehensive optimization framework that can be used to determine the
      optimal 2D stochastic or deterministic sampling geometry, as well as to provide
      optimal reconstruction parameter values for guaranteeing image quality in the
      reconstructed images. METHODS: We investigate the use of frequency-space (k
      space) sampling based on: (i) 2D deterministic geometries of dyadic phase
      encoding (DPE) and spiral low pass (SLP) geometries, and (ii) 2D stochastic
      geometries based on random phase encoding (RPE) and random samples on a PDF
      (RSP). Overall, we consider over 36 frequency-sampling geometries at different
      sampling rates. For each geometry, we compute optimal reconstructions of single
      BOLD fMRI ON & OFF images, as well as BOLD fMRI activity maps based on the
      difference between the ON and OFF images. We also provide an optimization
      framework for determining the optimal parameters and sampling geometry prior to
      scanning. RESULTS: For each geometry, we show that reconstruction parameter
      optimization converged after just a few iterations. Parameter optimization led to
      significant image quality improvements. For activity detection, retaining only
      20.3% of the samples using SLP gave a mean PSNR value of 57.58 dB. We also
      validated this result with the use of the Structural Similarity Index Matrix
      (SSIM) image quality metric. SSIM gave an excellent mean value of 0.9747 (max =
      1). This indicates that excellent reconstruction results can be achieved. Median
      parameter values also gave excellent reconstruction results for the ON/OFF images
      using the SLP sampling geometry (mean SSIM > =0.93). Here, median parameter
      values were obtained using mean-SSIM optimization. This approach was also
      validated using leave-one-out. CONCLUSIONS: We have found that compressive
      sensing parameter optimization can dramatically improve fMRI image reconstruction
      quality. Furthermore, 2D MRI scanning based on the SLP geometries consistently
      gave the best image reconstruction results. The implication of this result is
      that less complex sampling geometries will suffice over random sampling. We have
      also found that we can obtain stable parameter regions that can be used to
      achieve specific levels of image reconstruction quality when combined with
      specific k-space sampling geometries. Furthermore, median parameter values can be
      used to obtain excellent reconstruction results.

PMID- 22607469
TI  - Sample prefractionation for mass spectrometry quantification of low-abundance
      membrane proteins.
AB  - Use of stable isotope-labeled full-length proteins as an internal standard prior
      to multiple reaction monitoring (MRM) analysis enables prefractionation of the
      target proteins and quantification of those low-abundance proteins, which cannot
      be reached without biological sample enrichment. In terms of membrane proteins,
      this benefit can be used if a sample processing workflow allows entire
      solubilization of membrane proteins. We have developed a universal workflow for
      sample processing and enrichment by optimizing washing and solubilization
      conditions and implementing sample fractionation by Whole Gel Eluter. The
      optimized protocol was applied to various membrane-bound cytochromes P450 (CYPs)
      and their electron transferring protein partners, cytochrome P450 reductase
      (CPR), ferredoxin reductase (FdR), and ferredoxin (Fdx), all important proteins
      for cholesterol elimination from different organs. Both, weakly associated (CPR
      and FdR) and tightly associated (CYP7B1, CYP11A1, CYP27A1, and CYP46A1) membrane
      proteins were quantified. Measurements were performed on three human tissues
      (temporal lobe of the brain, retina, and retinal pigment epithelium) obtained
      from multiple donors. The biological implications of our quantitative
      measurements are also discussed.

PMID- 22607470
TI  - Genetic basis of unstable expression of high gamma-tocopherol content in
      sunflower seeds.
AB  - BACKGROUND: Tocopherols are natural antioxidants with both in vivo (vitamin E)
      and in vitro activity. Sunflower seeds contain predominantly alpha-tocopherol
      (>90% of total tocopherols), with maximum vitamin E effect but lower in vitro
      antioxidant action than other tocopherol forms such as gamma-tocopherol.
      Sunflower germplasm with stable high levels of gamma-tocopherol (>85%) has been
      developed. The trait is controlled by recessive alleles at a single locus Tph2
      underlying a gamma-tocopherol methyltransferase (gamma-TMT). Additionally,
      unstable expression of increased gamma-tocopherol content in the range from 5 to
      85% has been reported. The objective of this research was to determine the
      genetic basis of unstable expression of high gamma-tocopherol content in
      sunflower seeds. RESULTS: Male sterile plants of nuclear male sterile line
      nmsT2100, with stable high gamma-tocopherol content, were crossed with plants of
      line IAST-1, with stable high gamma-tocopherol content but derived from a
      population that exhibited unstable expression of the trait. F2 seeds showed
      continuous segregation for gamma-tocopherol content from 1.0 to 99.7%. Gamma
      tocopherol content in F2 plants (average of 24 individual F3 seeds) segregated
      from 59.4 to 99.4%. A genetic linkage map comprising 17 linkage groups (LGs) was
      constructed from this population using 109 SSR and 20 INDEL marker loci,
      including INDEL markers for tocopherol biosynthesis genes. QTL analysis revealed
      a major QTL on LG 8 that corresponded to the gamma-TMT Tph2 locus, which
      suggested that high gamma-tocopherol lines nmsT2100 and IAST-1 possess different
      alleles at this locus. Modifying genes were identified at LGs 1, 9, 14 and 16,
      corresponding in most cases with gamma-TMT duplicated loci. CONCLUSIONS: Unstable
      expression of high gamma-tocopherol content is produced by the effect of
      modifying genes on tph2a allele at the gamma-TMT Tph2 gene. This allele is
      present in line IAST-1 and is different to allele tph2 present in line nmsT2100,
      which is not affected by modifying genes. No sequence differences at the gamma
      TMT gene were found associated to allelic unstability. Our results suggested that
      modifying genes are mostly epistatically interacting gamma-TMT duplicated loci.

PMID- 22607471
TI  - Genome-wide identification and analysis of microRNA responding to long-term
      waterlogging in crown roots of maize seedlings.
AB  - MicroRNAs (miRNAs) are critical post-transcriptional modulators of gene
      expression involving in plant responses to abiotic stress. However, the
      regulation of miRNA in the morphological response to waterlogging is poorly
      understood in maize. In this study, we detected miRNAs and their targets that
      expressed in waterlogged crown roots of maize seedlings in two inbred lines (Hz32
      and Mo17) by RNA sequencing. A total of 61 mature miRNAs were found including 36
      known maize (zma) miRNAs and 25 potential novel miRNA candidates. Comparison of
      miRNA expression in both waterlogged and control crown roots revealed 32
      waterlogging-responsive miRNAs, most were consistently downregulated under
      waterlogging in the two inbred lines. We identified the miRNA targets through
      degradome sequencing. Many known miRNA targets involving in transcription
      regulation and reactive oxygen species elimination were found in the degradome
      libraries, and 17 targets of 10 newly detected miRNAs were identified as well.
      Moreover, the miRNA-mediated pathways that respond to waterlogging and regulate
      the induction of crown roots were discussed. This study is a comprehensive survey
      of responsive miRNAs in waterlogged maize crown roots. The results will help to
      understand the miRNA expression in response to waterlogging and miRNA-mediated
      regulation of morphological adaptation to waterlogging in maize.

PMID- 22607472
TI  - Bicyclic C21 terpenoids from the marine sponge Clathria compressa.
AB  - Three new bicyclic C(21) terpenoids, clathric acid (1) and two N-acyl taurine
      derivatives, clathrimides A (2) and B (3), were isolated from the marine sponge
      Clathria compressa. The structures of these compounds were elucidated by
      interpretation of spectroscopic data. Clathric acid showed mild antibacterial
      activity against several Gram-positive bacteria.

PMID- 22607473
TI  - Tight-binding inhibitors efficiently inactivate both reaction centers of
      monomeric Plasmodium falciparum glyoxalase 1.
AB  - Glucose consumption and therefore methylglyoxal production of human erythrocytes
      increase significantly upon infection with malaria parasites. The glyoxalase
      systems of the host-parasite unit cope with this metabolic challenge by
      catalyzing the removal of harmful methylglyoxal. Thus, glyoxalase 1 from the
      malaria parasite Plasmodium falciparum (PfGlo1) could be a promising drug target.
      However, the enzyme has two different active sites and their simultaneous
      inactivation is considered challenging. Here, we describe the inactivation of
      PfGlo1 by two glyoxalase-specific tight-binding inhibitors with nanomolar
      K(i)(app) values and noncompetitive inhibition patterns. The inhibitors do not
      discriminate between the high-affinity and the high-activity conformations of
      PfGlo1, but seem to stabilize or trigger a conformational change in analogy with
      the substrate. In summary, we have characterized the most potent inhibitors of
      PfGlo1 known to date.

PMID- 22607474
TI  - Content of maternal open-ended questions and statements in reminiscing with their
      4-year-olds: links with independence and interdependence orientation in European
      contexts.
AB  - Mother's open-ended questions and elaborative statements during reminiscing were
      analysed for their content (child agency, co-agency, non-social, and social
      context) in three cultural contexts. Participants were 115 mothers and their 4
      year-old children: 35 dyads from Berlin, Germany, 42 from Stockholm, Sweden, and
      38 from Tallinn, Estonia. Across samples the most prominent content was talk
      about non-social context followed by co-agency and child agency. Tallinn mothers
      asked the children to talk about themselves, and Berlin mothers asked the
      children to talk about themselves together with other people, more frequently
      than they talked about these contents themselves. The content was related to the
      cultural orientations of mothers assessed through questionnaires: the Berlin
      mothers whose independence/ interdependence ratio was higher talked less about
      other people and asked the children fewer questions about other people; the
      Stockholm mothers with a higher independence/interdependence ratio talked more
      about child agency. In Tallinn both correlations existed on a trend level. The
      results are discussed in the light of common conversational practices and
      mothers' orientation to independence and interdependence in these cultural
      contexts.

PMID- 22607475
TI  - Longitudinal study on transmission of MRSA CC398 within pig herds.
AB  - ABSBACKGROUND: Since the detection of MRSA CC398 in pigs in 2004, it has emerged
      in livestock worldwide. MRSA CC398 has been found in people in contact with
      livestock and thus has become a public health issue. Data from a large-scale
      longitudinal study in two Danish and four Dutch pig herds were used to quantify
      MRSA CC398 transmission rates within pig herds and to identify factors affecting
      transmission between pigs. RESULTS: Sows and their offspring were sampled at
      varying intervals during a production cycle. Overall MRSA prevalence of sows
      increased from 33% before farrowing to 77% before weaning. Overall MRSA
      prevalence of piglets was>60% during the entire study period. The recurrent
      finding of MRSA in the majority of individuals indicates true colonization or
      might be the result of contamination. Transmission rates were estimated using a
      Susceptible-Infectious-Susceptible (SIS-)model, which resulted in values of the
      reproduction ratio (R0) varying from 0.24 to 8.08. Transmission rates were higher
      in pigs treated with tetracyclins and beta-lactams compared to untreated pigs
      implying a selective advantage of MRSA CC398 when these antimicrobials are used.
      Furthermore, transmission rates were higher in pre-weaning pigs compared to post
      weaning pigs which might be explained by an age-related susceptibility or the
      presence of the sow as a primary source of MRSA CC398. Finally, transmission
      rates increased with the relative increase of the infection pressure within the
      pen compared to the total infection pressure, implying that within-pen
      transmission is a more important route compared to between-pen transmission and
      transmission through environmental exposure. CONCLUSION: Our results indicate
      that MRSA CC398 is able to spread and persist in pig herds, resulting in an
      endemic situation. Transmission rates are affected by the use of selective
      antimicrobials and by the age of pigs.

PMID- 22607476
TI  - VIPER: a visualisation tool for exploring inheritance inconsistencies in
      genotyped pedigrees.
AB  - BACKGROUND: Pedigree genotype datasets are used for analysing genetic inheritance
      and to map genetic markers and traits. Such datasets consist of hundreds of
      related animals genotyped for thousands of genetic markers and invariably contain
      multiple errors in both the pedigree structure and in the associated individual
      genotype data. These errors manifest as apparent inheritance inconsistencies in
      the pedigree, and invalidate analyses of marker inheritance patterns across the
      dataset. Cleaning raw datasets of bad data points (incorrect pedigree
      relationships, unreliable marker assays, suspect samples, bad genotype results
      etc.) requires expert exploration of the patterns of exposed inconsistencies in
      the context of the inheritance pedigree. In order to assist this process we are
      developing VIPER (Visual Pedigree Explorer), a software tool that integrates an
      inheritance-checking algorithm with a novel space-efficient pedigree
      visualisation, so that reported inheritance inconsistencies are overlaid on an
      interactive, navigable representation of the pedigree structure. METHODS AND
      RESULTS: This paper describes an evaluation of how VIPER displays the different
      scales and types of dataset that occur experimentally, with a description of how
      VIPER's display interface and functionality meet the challenges presented by such
      data. We examine a range of possible error types found in real and simulated
      pedigree genotype datasets, demonstrating how these errors are exposed and
      explored using the VIPER interface and we evaluate the utility and usability of
      the interface to the domain expert.Evaluation was performed as a two stage
      process with the assistance of domain experts (geneticists). The initial
      evaluation drove the iterative implementation of further features in the software
      prototype, as required by the users, prior to a final functional evaluation of
      the pedigree display for exploring the various error types, data scales and
      structures. CONCLUSIONS: The VIPER display was shown to effectively expose the
      range of errors found in experimental genotyped pedigrees, allowing users to
      explore the underlying causes of reported inheritance inconsistencies. This
      interface will provide the basis for a full data cleaning tool that will allow
      the user to remove isolated bad data points, and reversibly test the effect of
      removing suspect genotypes and pedigree relationships.

PMID- 22607477
TI  - Autosomal genetic diversity in non-breed horses from eastern Eurasia provides
      insights into historical population movements.
AB  - Many events in the history of eastern Eurasia, including the process of
      domestication itself, the initial spread of domestic horses and subsequent
      movements, are believed to have affected the genetic structure of domestic horse
      populations in this area. We investigated levels of within- and between
      population genetic diversity in 'non-breed horses' (working horses sampled in
      remote areas) from 17 locations in Asia and parts of Eastern Europe, using 26
      autosomal microsatellite loci. Non-breed horses have not been subject to the same
      intensity of artificial selection and closed breeding as have most breed animals
      and are thus expected to better reflect the population history of domestic
      horses. Despite geographic distances of between 300 and 7000 km between sampling
      locations, pairwise F (ST) was very low (range: <0.001 to -0.033), suggesting
      historically high levels of gene flow. Our analyses of non-breed horses revealed
      a pattern of isolation by distance and a significant decline in genetic diversity
      (expected heterozygosity and allelic richness) from east to west, consistent with
      a westward expansion of horses out of East Asia. Although the timing of this
      putative expansion is unclear, our results highlight the benefit of studying
      animals that do not belong to particular breeds when investigating aspects of a
      population's history.

PMID- 22607478
TI  - Investigation of factor affecting health-related quality of life in head and neck
      cancer patients.
AB  - OBJECTIVES: Head and neck cancer (HNC) patients have profound illness of
      physical, social and psychological factors that affects quality of life (QOL).
      The purpose of this study is to investigate the factors affecting HRQL in
      patients with intra-oral prostheses. BACKGROUND: Some cross-sectional studies
      have been performed to investigate HRQL in patients with HNC, but these studies
      did not report in detail how factors affect the HRQL of maxillectomy and
      mandibulectomy and/or glossectomy patients. MATERIALS AND METHODS: The University
      of Washington Quality of Life version 4 questionnaires (Japanese version) was
      administered to 50 maxillectomy and 50 mandibulectomy and/or glossectomy patients
      with intra-oral prostheses who were selected according to inclusion and exclusion
      criteria. Gathered data were statistically analyzed to investigate how a number
      of factors, namely, age, sex, pathologic diagnosis, neck dissection, resection
      size, radiotherapy and dental condition affect HRQL. RESULTS: In the maxillectomy
      patients, there were no significant differences between malignant and benign
      tumor in pathological diagnosis or between dentate and edentulous in dental
      condition. Age, sex, neck dissection and radiotherapy affected HRQL. In the
      mandibulectomy and/or glossectomy patients, there was no significant difference
      between dentate and edentulous in dental condition. Age, sex, glossectomy, neck
      dissection and radiotherapy affected HRQL. CONCLUSIONS: The factors affecting
      HRQL in the maxillectomy patients were different from those in the mandibulectomy
      and/or glossectomy patients. Though they wore stable prostheses; we were still
      able to show that resection size, radiotherapy and neck dissection affected HRQL.

PMID- 22607480
TI  - Automated dead-end ultrafiltration of large volume water samples to enable
      detection of low-level targets and reduce sample variability.
AB  - AIMS: A Portable Multi-use Automated Concentration System (PMACS) concentrates
      micro-organisms from large volumes of water through automated dead-end
      ultrafiltration and backflushing. The ability to detect microbial targets from
      ground, surface and cooling tower waters collected using standard methods was
      compared with samples from the PMACS in this study. METHODS AND RESULTS: PMACS
      (100 l) and standard grab samples (100-500 ml) were collected from sites in
      Florida and South Carolina, USA. Samples were analysed for the presence of faecal
      indicator bacteria (FIB; ground and surface water) or Legionella pneumophila (Lp;
      cooling tower water). FIB were enumerated by growth on selective media following
      membrane filtration or in IDEXX defined substrate media. Lp cells were detected
      by direct fluorescence immunoassay using FITC-labelled monoclonal antibodies
      targeting serogroups 1, 2, 4 and 6. FIB were found in PMACS samples from ground
      and surface waters when their concentrations were below detection limits in grab
      samples. The concentrations of Lp in cooling tower samples collected over 5
      months were more consistent in PMACS samples than grab samples. CONCLUSIONS:
      These data demonstrate that PMACS concentration is advantageous for water
      monitoring. FIB were detected in PMACS samples when their concentrations were
      below the detection limits of the standard methods used. PMACS processing
      provided more representative samples of cooling tower waters reducing sample
      variability during long-term monitoring. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This study highlights the utility of PMACS processing for enhanced monitoring of
      water for low-level microbial targets and for reducing sample variability in long
      term monitoring programmes.

PMID- 22607479
TI  - Budesonide/formoterol maintenance and reliever therapy in Asian patients (aged
      >=16 years) with asthma: a sub-analysis of the COSMOS study.
AB  - BACKGROUND: The combination of an inhaled corticosteroid (ICS), budesonide, and a
      rapid long-acting beta(2)-agonist (LABA), formoterol, in a single inhaler for use
      as maintenance and reliever therapy (Symbicort Turbuhaler SMARTTM) effectively
      achieves a high level of asthma control and reduces exacerbations and asthma
      related hospitalizations. The COSMOS study, a multinational, 12-month study (N =
      2143), compared budesonide/formoterol maintenance and reliever therapy with
      salmeterol/fluticasone propionate plus as-needed salbutamol, allowing physicians
      to modify maintenance doses of both combinations according to routine clinical
      practice. OBJECTIVE: The aim of this post hoc sub-group analysis of the COSMOS
      study is to provide focused data on budesonide/formoterol maintenance and
      reliever therapy compared with salmeterol/fluticasone propionate plus as-needed
      salbutamol in patients (aged >=16 years) enrolled across Asian countries,
      specifically China, Korea, Taiwan and Thailand. METHODS: This sub-analysis of the
      COSMOS study concerns all 404 randomized patients >=16 years of age (mean forced
      expiratory volume in 1 second [FEV(1)] 69.1%) who were recruited from Asian
      countries. Patients received either budesonide/formoterol (Symbicort Turbuhaler
      SMARTTM, n = 198), starting dose 160 mg/4.5 mg two inhalations twice daily (bid)
      [plus additional as-needed inhalations], or salmeterol/fluticasone propionate
      (Seretide((r)) Diskus((r)), n = 206), starting dose 50 mg/250 mg bid (plus
      salbutamol [Ventolin((r))] as needed). Maintenance doses could be titrated by
      clinicians after the first 4 weeks (budesonide/formoterol maintenance plus as
      needed, n = 198; salmeterol/fluticasone propionate plus salbutamol, n = 206). To
      allow for free adjustment in maintenance doses in both arms, the trial was
      performed open-label; maintenance doses could be titrated by clinicians after the
      first 4 weeks. The time to first severe exacerbation (defined as deterioration in
      asthma resulting in hospitalization/emergency room treatment, oral
      corticosteroids for >=3 days or unscheduled visit leading to treatment change)
      was the primary variable. RESULTS: The time to first severe exacerbation was
      prolonged in patients using maintenance plus as-needed budesonide/formoterol
      compared with salmeterol/fluticasone propionate plus salbutamol (log-rank p =
      0.024). The risk of a first exacerbation was reduced by 44% (hazard ratio 0.56;
      95% confidence interval [CI] 0.32, 0.95; p = 0.033) in patients using the
      adjusted budesonide/formoterol regimen versus titrated salmeterol/fluticasone
      propionate. The overall exacerbation rates were 0.16 versus 0.26 events/patient
      year, respectively, with a 38% reduction (rate ratio 0.62/patient/year; 95% CI
      0.41, 0.94; p = 0.024) in favour of the budesonide/formoterol regimen. Compared
      with baseline, both regimens provided clinically relevant improvements in asthma
      control, quality of life and FEV(1); no statistically significant differences
      between the treatment groups were observed. Mean adjusted (standard deviation)
      ICS dose (expressed as beclomethasone dose equivalents) during treatment,
      including as-needed budesonide doses, was 944 (281) and 1034 (394) MUg/day,
      respectively, in patients using maintenance plus as-needed budesonide/formoterol
      compared with salmeterol/fluticasone propionate. CONCLUSION: In patients (aged
      >=16 years) enrolled from Asian countries as part of the COSMOS study, the
      budesonide/formoterol maintenance and reliever regimen was associated with a
      lower future risk of exacerbations versus the physicians' free choice of
      salmeterol/fluticasone propionate dose plus salbutamol. Single inhaler
      combination treatment with maintenance plus as-needed budesonide/formoterol was
      also at least as efficacious as salmeterol/fluticasone propionate dose plus
      salbutamol in improving current asthma control.

PMID- 22607482
TI  - The prognostic profile of subfertile couples and treatment outcome after
      expectant management, intrauterine insemination and in vitro fertilisation: a
      study protocol for the meta-analysis of individual patient data.
AB  - OBJECTIVE: The current evidence concerning the best treatment option for couples
      with unexplained and male subfertility is inconclusive. Most studies that have
      evaluated the effectiveness of treatment options, such as expectant management
      (EM), intrauterine insemination (IUI), with or without controlled ovarian
      stimulation (COS), and in vitro fertilisation (IVF), have not taken the couples'
      prognosis into account. It is very likely that the individual prognosis of the
      couple influences the effect of treatment. Individual patient data analyses allow
      us to take these prognostic factors into account, and to evaluate their effect on
      treatment outcome. This study aims to use anonymised data from relevant published
      trials to perform an individual patient data meta-analysis, evaluating the effect
      of couples' prognosis on the effectiveness of EM, IUI, with or without COS, and
      IVF. METHODS: Based on earlier systematic reviews and an updated search,
      randomised controlled trials will be considered for inclusion. Untreated
      subfertile couples with unexplained or male subfertility included in trials
      comparing EM, IUI, with or without COS, and IVF are included. Authors of the
      included studies will be invited to share their original anonymised data. The
      data will be assessed on validity, quality and completeness. The prognosis of the
      individual couple will be calculated with existing prognostic models. The effect
      of the prognosis on treatment outcome will be analysed with marker-by-treatment
      predictiveness curves, illustrating the effect of prognosis on treatment outcome.
      This study is registered in PROSPERO (registration number CRD42011001832).
      CONCLUSION: Ultimately, this study may help to select the appropriate fertility
      treatment, tailored to the needs of an individual couple.

PMID- 22607485
TI  - Structure and photovoltaic properties of ZnO nanowire for dye-sensitized solar
      cells.
AB  - Aligned ZnO nanowires with different lengths (1 to approximately 4 MUm) have
      been deposited on indium titanium oxide-coated glass substrates by using the
      solution phase deposition method for application as a work electrode in dye
      sensitized solar cells (DSSC). From the results, the increases in length of zinc
      oxide (ZnO) nanowires can increase adsorption of the N3 dye through ZnO nanowires
      to improve the short-circuit photocurrent (Jsc) and open-circuit voltage (Voc),
      respectively. However, the Jsc and Voc values of DSSC with ZnO nanowires length
      of 4.0 MUm (4.8 mA/cm2 and 0.58 V) are smaller than those of DSSC with ZnO
      nanowires length of 3.0 MUm (5.6 mA/cm2 and 0.62 V). It could be due to the
      increased length of ZnO nanowires also resulted in a decrease in the
      transmittance of ZnO nanowires thus reducing the incident light intensity on the
      N3 dye. Optimum power conversion efficiency (eta) of 1.49% was obtained in a DSSC
      with the ZnO nanowires length of 3 MUm.

PMID- 22607481
TI  - Drug discovery technologies and strategies for Machupo virus and other New World
      arenaviruses.
AB  - INTRODUCTION: Seven arenaviruses cause viral hemorrhagic fever in humans: the Old
      World arenaviruses Lassa and Lujo, and the New World Clade B arenaviruses Machupo
      (MACV), Junin (JUNV), Guanarito (GTOV), Sabia (SABV), and Chapare (CHPV). All of
      these viruses are Risk Group 4 biosafety pathogens. MACV causes human disease
      outbreak with high case-fatality rates. To date, at least 1,200 cases with ~200
      fatalities have been recorded. AREAS COVERED: This review summarizes available
      systems and technologies for the identification of antivirals against MACV.
      Furthermore, the article summarizes animal models that have been used for the in
      vivo evaluation of novel inhibitors. The article highlights present treatments
      for arenaviral diseases and provides an overview of efficacious small molecules
      and other therapeutics reported to date. Finally, the article summarizes
      strategies to identify novel inhibitors for anti-arenaviral therapy. EXPERT
      OPINION: New high-throughput approaches to quantitate infection rates of
      arenaviruses, as well as viruses modified to carry reporter genes, will
      accelerate compound screens and drug discovery efforts. RNAi, gene expression
      profiling and proteomics studies will identify host targets for therapeutic
      intervention. New discoveries in the cell entry mechanism of MACV and other
      arenaviruses as well as extensive structural studies of arenaviral L and NP could
      facilitate the rational design of antivirals effective against all pathogenic New
      World arenaviruses.

PMID- 22607484
TI  - Decreased platelet adhesion and enhanced endothelial cell functions on nano and
      submicron-rough titanium stents.
AB  - Endothelialization of a vascular stent is a critical step to prevent late stent
      thrombosis. In this study, electron beam deposition was utilized to create
      different scales of roughness on titanium stents, including flat features (F-Ti),
      a mixture of nanometer and submicron features (S-Ti), and nanometer features (N
      Ti). The role of stent surface roughness on initial protein adsorption, platelet
      adhesion, rat aortic endothelial cell adhesion, migration, and nitric
      acid/endothelin-1 secretion was investigated in vitro. Results revealed the
      highest endothelial cell attachment on S-Ti after 4 h. Moreover, under flow
      conditions, the endothelial cell layer remained the most intact on S-Ti. These
      results were positively correlated with improved vitronectin adsorption on S-Ti.
      Endothelial cells also showed the fastest migration on S-Ti of all the samples
      over a 96 h time period. Endothelial cells on S-Ti exhibited the highest nitric
      acid/endothelin-1 ratio of all the samples, indicating potentially the best
      antithrombic endothelial cellular phenotype. This study also revealed the lowest
      platelet adhesion on S-Ti of all the samples. In summary, without using
      pharmaceutical agents, significantly less platelet and greater endothelial
      responses on nanometer to submicron rough titanium were observed in this study
      compared to flat titanium and, thus, nanometer to submicron surface features on
      titanium should be further studied for vascular stent applications.

PMID- 22607483
TI  - Predictors for length of hospital stay in patients with community-acquired
      pneumonia: results from a Swiss multicenter study.
AB  - BACKGROUND: Length of hospital stay (LOS) in patients with community-acquired
      pneumonia (CAP) is variable and directly related to medical costs. Accurate
      estimation of LOS on admission and during follow-up may result in earlier and
      more efficient discharge strategies. METHODS: This is a prospective multicenter
      study including patients in emergency departments of 6 tertiary care hospitals in
      Switzerland between October 2006 and March 2008. Medical history, clinical data
      at presentation and health care insurance class were collected. We calculated
      univariate and multivariate cox regression models to assess the association of
      different characteristics with LOS. In a split sample analysis, we created two
      LOS prediction rules, first including only admission data, and second including
      also additional inpatient information. RESULTS: The mean LOS in the 875 included
      CAP patients was 9.8 days (95%CI 9.3-10.4). Older age, respiratory rate >20 pm,
      nursing home residence, chronic pulmonary disease, diabetes, multilobar CAP and
      the pneumonia severity index class were independently associated with longer LOS
      in the admission prediction model. When also considering follow-up information,
      low albumin levels, ICU transfer and development of CAP-associated complications
      were additional independent risk factors for prolonged LOS. Both weighted
      clinical prediction rules based on these factors showed a high separation of
      patients in Kaplan Meier Curves (p logrank <0.001 and <0.001) and a good
      calibration when comparing predicted and observed results. CONCLUSIONS: Within
      this study we identified different baseline and follow-up characteristics to be
      strong and independent predictors for LOS. If validated in future studies, these
      factors may help to optimize discharge strategies and thus shorten LOS in CAP
      patients.

PMID- 22607486
TI  - Rumination, gender, and depressive symptoms associated with caregiving strain in
      bipolar disorder.
AB  - OBJECTIVE: To evaluate the associations between indices of caregiving strain,
      ruminative style, depressive symptoms, and gender among family members of
      patients with bipolar disorder. METHOD: One hundred and fifty primary caregivers
      of patients enrolled in the Systematic Treatment Enhancement Program for Bipolar
      Disorder (STEP-BD) participated in a cross-sectional study to evaluate the role
      of ruminative style in maintaining depressive symptoms associated with caregiving
      strain. Patient lifetime diagnosis and current episode status were evaluated by
      the Affective Disorder Evaluation and the Clinical Monitoring Form. Caregivers
      were evaluated within 30 days of the patient on measures of family strain,
      depressive symptoms, and ruminative style. RESULTS: Men and women did not differ
      on depression, caregiver strain, or ruminative style scores. Scores suggest an
      overall mild level of depression and moderate caregiver strain for the sample.
      Greater caregiver strain was significantly associated (P<0.05) with rumination
      and level of depressive symptoms, controlling for patient clinical status and
      demographic variables. Rumination reduced the apparent association between strain
      and depression by nearly half. Gender was not significantly associated with
      depression or rumination. CONCLUSION: Rumination helps explain depressive
      symptoms experienced by both male and female caregivers of patients with bipolar
      disorder. Interventions for caregivers targeted at decreasing rumination should
      be considered.

PMID- 22607487
TI  - Local electrogram delay recorded from left ventricular lead at implant predicts
      response to cardiac resynchronization therapy: retrospective study with 1 year
      follow up.
AB  - BACKGROUND: Considerable proportion of patients does not respond to the cardiac
      resynchronization therapy (CRT). This study investigated clinical relevance of
      left ventricular electrode local electrogram delay from the beginning of QRS
      (QLV). We hypothesized that longer QLV indicating more optimal lead placement in
      the late activated regions is associated with the higher probability of positive
      CRT response. METHODS: We conducted a retrospective, single-centre analysis of
      161 consecutive patients with heart failure and LBBB or nonspecific
      intraventricular conduction delay (IVCD) treated with CRT. We routinely intend to
      implant the LV lead in a region with long QLV. Clinical response to CRT, left
      ventricular (LV) reverse remodelling (i.e. decrease in LV end-systolic diameter -
      LVESD >=10%) and reduction in plasma level of NT-proBNP >30% at 12-month post
      implant were the study endpoints. We analyzed association between pre-implant
      variables and the study endpoints. RESULTS: Clinical CRT response rate reached
      58%, 84% and 92% in the lowest (<=105 ms), middle (106-130 ms) and the highest
      (>130 ms) QLV tertile (p < 0.0001), respectively. Longer QRS duration (p =
      0.002), smaller LVESD and a non-ischemic cardiomyopathy (both p = 0.02) were also
      univariately associated with positive clinical CRT response. In a multivariate
      analysis, QLV remained the strongest predictor of clinical CRT response (p <
      0.00001), followed by LVESD (p = 0.01) and etiology of LV dysfunction (p = 0.04).
      Comparable predictive power of QLV for LV reverse remodelling and NT-proBNP
      response rates was observed. CONCLUSION: LV lead position assessed by duration of
      the QLV interval was found the strongest independent predictor of beneficial
      clinical response to CRT.

PMID- 22607488
TI  - Isolation of an extremely boron-tolerant strain of  Bacillus firmus.
AB  - A strain of Bacillus firmus (designated strain KC) isolated from a boron (B) mine
      in California exhibited extreme tolerance to B, provided it was first acclimated
      at intermediate B supply concentrations. Strain KC tolerated up to 1000 mmol/L B
      (boric acid-B) and 1800 mmol/L B (sodium tetraborate-B), and attained the
      greatest growth (as measured by absorbance) at 300 mmol/L B. Despite its extreme
      tolerance to high B, there was no evidence that it was able to remove significant
      quantities of B from the growth media, suggesting that strain KC is not likely to
      be useful for the removal of B from wastewaters in an engineered bioreactor.

PMID- 22607489
TI  - Dural arteriovenous fistula involving the anterior condylar canal.
AB  - Dural arteriovenous fistula (DAVF) of the anterior condylar canal is a rare
      subgroup of posterior fossa DAVF. Successful treatment of this DAVF requires an
      accurate image diagnosis and the knowledge of the anatomy of the anterior
      condylar confluent. We present the imaging features of angiography and MR
      angiography of a 54-year-old man, who presented progressive right synchronous
      tinnitus due to a DAVF of the anterior condylar confluent, successfully treated
      by transvenous embolization. 

PMID- 22607490
TI  - Effect of sulfur and nitrogen fertilization on the content of nutritionally
      relevant carotenoids in spinach ( Spinacia oleracea ).
AB  - Spinach is an important dietary source of lutein and beta-carotene. Their
      synthesis is closely linked to chlorophyll synthesis and dependent upon an
      adequate supply of sulfur and nitrogen. Soils may become sulfur-deficient during
      winter because microorganisms convert atmospheric SO2 less efficiently to
      sulfate. The influence of sulfur and nitrogen fertilization on the carotenoid and
      chlorophyll contents of spinach grown in summer or winter was investigated.
      Carotenoid and chlorophyll levels were positively correlated. Lutein and beta
      carotene were 25% higher in summer than in winter. Winter levels were increased
      by 35-40% by sulfur fertilization in one location but not in the other, with the
      impact depending upon soil type, growing location, and atmospheric conditions.
      Carotenoids were little or not affected by nitrogen addition in winter or sulfur
      addition in summer. It is concluded that sulfur fertilization of spinach in
      winter may modestly increase carotenoids but high carotenoid levels are best
      assured with carotenoid-rich cultivars grown in summer. 

PMID- 22607491
TI  - Active sites for outer-sphere, inner-sphere, and complex multistage
      electrochemical reactions at polycrystalline boron-doped diamond electrodes
      (pBDD) revealed with scanning electrochemical cell microscopy (SECCM).
AB  - The local rate of heterogeneous electron transfer (HET) at polycrystalline boron
      doped diamond (pBDD) electrodes has been visualized at high spatial resolution
      for various aqueous electrochemical reactions, using scanning electrochemical
      cell microscopy (SECCM), which is a technique that uses a mobile pipet-based
      electrochemical cell as an imaging probe. As exemplar systems, three important
      classes of electrode reactions have been investigated: outer-sphere (one-electron
      oxidation of ferrocenylmethyltrimethylammonium (FcTMA(+))), inner-sphere (one
      electron oxidation of Fe(2+)), and complex processes with coupled electron
      transfer and chemical reactions (oxidation of serotonin). In all cases, the
      pattern of reactivity is similar: the entire pBDD surface is electroactive, but
      there are variations in activity between different crystal facets which correlate
      directly with differences in the local dopant level, as visualized qualitatively
      by field-emission scanning electron microscopy (FE-SEM). No evidence was found
      for enhanced activity at grain boundaries for any of the reactions. The case of
      serotonin oxidation is particularly interesting, as this process is known to lead
      to deterioration of the electrodes, because of blocking by reaction products, and
      therefore cannot be studied with conventional scanning electrochemical probe
      microscopy (SEPM) techniques. Yet, we have found this system nonproblematic to
      study, because the meniscus of the scanning pipet is only in contact with the
      surface investigated for a brief time and any blocking product is left behind as
      the pipet moves to a new location. Thus, SECCM opens up the possibility of
      investigating and visualizing much more complex heterogeneous electrode reactions
      than possible presently with other SEPM techniques.

PMID- 22607493
TI  - Structure, energetics, and infrared spectra of weakly bound HC(2n+1)N...HCl
      complexes. A theoretical study.
AB  - Three model systems, HCN...HCl, HC(3)N...HCl, and HC(5)N...HCl, have been
      investigated computationally with the use of the second-order Moller-Plesset
      (MP2) and the coupled cluster (with single and double excitations and
      noniterative inclusion of triples) methods. The global minima are linear hydrogen
      bonded structures with HCl as a proton donor. Bent structures are proton-side
      complexes with HCl as an electron donor, while the bifurcated hydrogen bonds are
      predicted for t-shape complexes. One of the most important findings in this paper
      is that, according to symmetry-adapted perturbation analysis, the induction-to
      dispersion ratios are the biggest for linear complexes, and it is the most
      noticeable difference between linear, bent, and t-shape structures.

PMID- 22607492
TI  - Mortality and morbidity study of petrochemical employees in a polluted site.
AB  - BACKGROUND: The area of Gela was included among the 57 Italian polluted sites of
      national interest for environmental remediation because of its widespread
      contamination from a petrochemical complex. The present study investigates
      mortality and morbidity of the cohort of Gela petrochemical workers with the aim
      of disentangling occupational from residential risk. METHODS: Mortality was
      assessed for 5,627 men hired from 1960, year of the plant start-up, to 1993; it
      was followed up for vital status in the period 1960-2002. Morbidity was analysed
      for 5,431 workers neither dead nor lost to follow-up from 1960 to 2001 and was
      based on Hospital Discharge Records in the period 2001-2006. The work experience
      was classified in terms of job categories such as blue collars, white collars,
      and both--workers who shifted from blue to white collar (95%) or vice versa. An
      ad hoc mobility model was applied to define qualitative categories of residence
      in Gela, as residents and commuters. Standardized Mortality Ratios (SMRs) and
      Mortality Rate Ratios (MRRs) were computed, the latter by using a Poisson
      regression model. Morbidity was analyzed in terms of Hospital Discharge Odds
      Ratios (HDORs) through a logistic regression model. While performing the internal
      comparisons, white collars was the reference category for the job analysis, and
      commuters was the reference category for the residential analysis. RESULTS: In
      the light of epidemiological evidence about health risk from petrochemical
      industries in both occupational and environmental settings, and/or on the basis
      of information about occupational and residential contamination and health risk
      in the area of Gela, noteworthy results are shown for lung cancer [MRR: 2.11 (CI
      90%; 0.96-4.63) in blue collars; 1.71 (1.09-2.69) in residents], respiratory
      diseases [HDOR: 2.0 (1.0-3.0) in blue collars; 1.4 (0.96-2.06) in residents] and
      genitourinary diseases [HDOR: 1.34 (1.06-1.68) in blue collars; 1.23 (1.04-1.45)
      in residents]. CONCLUSIONS: The results support a role of the exposures in the
      occupational and residential settings, the latter due to the local ascertained
      contamination, in affecting the workers' health. These results underline the
      urgent need of water, soil, air and food-chain monitoring programs, to discover
      active sources of exposure and consequently define public health interventions.

PMID- 22607494
TI  - Response of mitochondrial antioxidant system and respiratory pathways to reactive
      nitrogen species in pea leaves.
AB  - Nitric oxide (NO) has emerged as an important signaling molecule in plants, but
      little is known about the effects of reactive nitrogen species in plant
      mitochondria. In this study, the effects of DETA-NONOate, a pure NO slow
      generator, and of SIN-1 (3-morpholinosydnonimine), a peroxynitrite producer, on
      the activities of respiratory pathways, enzymatic and non-enzymatic antioxidants
      have been investigated in isolated mitochondria from pea leaves. No significant
      changes in lipid peroxidation, protein oxidation or in ascorbate and glutathione
      redox state were observed after DETA-NONOate treatments whereas cytochrome
      pathway (CP) respiration was reversibly inhibited and alternative pathway (AP)
      respiration showed little inhibition. On the other hand, NO did not affect
      neither activities of Mn superoxide dismutase (Mn-SOD) nor enzymes involved in
      the ascorbate and glutathione regeneration in mitochondria except for ascorbate
      peroxidase (APX), which was reversely inhibited depending on ascorbate
      concentration. Finally, SIN-1 treatment of mitochondria produced a decrease in CP
      respiration, an increase in protein oxidation and strongly inhibited APX activity
      (90%), with glutathione reductase and dehydroascorbate reductase (DHAR) being
      moderately inhibited (30 and 20%, respectively). This treatment did not affect
      monodehydroascorbate reductase (MDHAR) and Mn-SOD activities. Results showed that
      mitochondrial nitrosative stress was not necessarily accompanied by oxidative
      stress. We suggest that NO-resistant AP and mitochondrial APX may be important
      components of the H(2) O(2) -signaling pathways under nitrosative stress induced
      by NO in this organelle. Also, MDHAR and DHAR, via ascorbate regeneration, could
      constitute an essential antioxidant defense together with Mn-SOD, against NO and
      ONOO(-)  stress in plant mitochondria.

PMID- 22607495
TI  - Diterpenoid alkaloids from the lateral root of Aconitum carmichaelii.
AB  - Twenty-six new diterpenoid alkaloids, 1-26 (1-4: hetisan-type C(20)-diterpenoid
      alkaloids; 5-26: aconitane C(19)-diterpenoid alkaloids), and two known analogues,
      hypaconitine 27 and benzoylmesaconine 28, have been isolated from a water extract
      of the lateral root of Aconitum carmichaelii. Compounds 7 and 8 are rare examples
      of conformational isomers obtained from the same material. The conformation and
      conformational transformation of ring A in the C(19)-diterpenoid alkaloids are
      discussed on the basis of NMR data analysis in combination with single-crystal X
      ray crystallography of 6 and 27 by anomalous scattering of Cu Kalpha radiation.
      In preliminary analgesic and toxicity assays, the isomer with ring A in the chair
      conformation (8 or 27) was found to be more active than that with ring A in the
      boat conformation (7 or 27a). In addition, 15, 16, and 19 showed neuroprotective
      activity.

PMID- 22607496
TI  - Pseudofolliculitis barbae induced by oral minoxidil.

PMID- 22607497
TI  - No indication of Coxiella burnetii infection in Norwegian farmed ruminants.
AB  - BACKGROUND: Infection with Coxiella burnetii, the cause of Q-fever, has never
      been detected in Norwegian animals. Recognising the increasing prevalence of the
      infection in neighbouring countries, the aim of the study was to perform a survey
      of Norwegian farmed ruminants for the prevalence of C. burnetii infection.
      RESULTS: Milk and blood samples from more than 3450 Norwegian dairy cattle herds,
      55 beef cattle herds, 348 dairy goat herds and 118 sheep flocks were
      serologically examined for antibodies against C. burnetii. All samples were
      negative for antibodies against C. burnetii. The estimated prevalences of
      infected herds were 0 (95% confidence interval: 0% - 0.12%), 0 (0% - 12%), 0 (0% 
      1.2%) and 0 (0% - 10%) for dairy cattle herds, beef cattle herds, goat herds and
      sheep flocks, respectively. CONCLUSIONS: The study indicates that the prevalence
      of C. burnetii infection in farmed Norwegian ruminants is low, and it cannot be
      excluded that Norway is free of the infection. It would be beneficial if Norway
      was able to maintain the current situation. Therefore, preventive measures should
      be continued.

PMID- 22607498
TI  - A chiral porous metal-organic framework for highly sensitive and enantioselective
      fluorescence sensing of amino alcohols.
AB  - A highly porous and fluorescent metal-organic framework (MOF), 1, was built from
      a chiral tetracarboxylate bridging ligand derived from 1,1'-bi-2-naphthol (BINOL)
      and a cadmium carboxylate infinite-chain secondary building unit. The
      fluorescence of 1 can be effectively quenched by amino alcohols via H-bonding
      with the binaphthol moieties decorating the MOF, leading to a remarkable chiral
      sensor for amino alcohols with greatly enhanced sensitivity and
      enantioselectivity over BINOL-based homogeneous systems. The higher detection
      sensitivity of 1 is due to a preconcentration effect by which the analytes are
      absorbed and concentrated inside the MOF channels, whereas the higher
      enantioselectivity of 1 is believed to result from enhanced chiral discrimination
      owing to the cavity confinement effect and the conformational rigidity of the
      BINOL groups in the framework. 1 was quenched by four chiral amino alcohols with
      unprecedentedly high Stern-Volmer constants of 490-31200 M(-1) and
      enantioselectivity ratios of 1.17-3.12.

PMID- 22607499
TI  - Micelle-like nanoassemblies based on polymer-drug conjugates as an emerging
      platform for drug delivery.
AB  - INTRODUCTION: During the past decades, polymer-drug conjugates are one of the
      hottest topics in novel drug development fields. Amphiphilic polymer-drug
      conjugates in aqueous solution could form micelles or micelle-like
      nanoassemblies. Compared with polymer-drug conjugates and the micelles into which
      drugs are physically entrapped, micelles or micelle-like nanoassemblies based on
      polymer-drug conjugates bring several additional advantages, including increased
      drug-loading capacity, enhanced intracellular uptake, reduced systemic toxicity,
      and improved therapeutic efficacy. AREAS COVERED: This review focuses on recent
      progress achieved in the research field of micelles or micelle-like
      nanoassemblies based on polymer-drug conjugates. Firstly, properties of polymers,
      drugs, and linkers which could be used to build polymer-drug conjugate micelles
      or micelle-like nanoassemblies are summarized. Then, the characterization methods
      are described. Finally, the drug-targeting mechanisms are discussed. Micelles or
      micelle-like nanoassemblies based on polymer-drug conjugates as an emerging
      platform have the potential to achieve medical treatments with enhanced
      therapeutic effect. EXPERT OPINION: The application of micelles or micelle-like
      nanoassemblies based on polymer-drug conjugates may give new life to old active
      compounds abandoned due to their low solubility problems. For clinical
      application, there is a need to further optimize the properties of the polymer,
      drug, and linker.

PMID- 22607500
TI  - Brain cancer in interventional cardiologists and physicians - is occupational
      radiation exposure the cause?

PMID- 22607501
TI  - Lumping and splitting in cardiovascular risk.

PMID- 22607502
TI  - PMR and GCA: steroids or bust.

PMID- 22607503
TI  - Lower urinary tract symptoms revisited.

PMID- 22607504
TI  - Antiphospholipid antibody testing - slow progress?

PMID- 22607505
TI  - A review of family history of cardiovascular disease: risk factor and research
      tool.
AB  - Family history (FH) studies have been used to quantify the heritable component of
      diseases for centuries. Genome-wide association studies (GWAS) in both coronary
      artery disease (CAD) and stroke have implicated several gene loci in these
      diseases and have shed light on biological mechanisms, but have not yet yielded
      fruit in terms of clinical application, partly because of the complexity of gene
      gene and gene-environment interactions. Family history studies remain the most
      accessible way of measuring the inherited component of a disease and they
      represent the overall interaction between environmental and genetic factors. The
      current knowledge base for FH of stroke and CAD and disease correlates are
      evaluated. FH of stroke and CAD are inconsistently recorded in clinical practice,
      partly because of lack of data regarding family history of stroke and CAD in
      prospective population studies. Future FH studies are necessary to characterise
      the role of FH in prognosis and risk prediction of contemporary populations, but
      also to guide future studies of genetics and epigenetics. In this article, the
      study design and methodology of family history studies are reviewed. The Oxford
      Vascular Study (OXVASC) is an ongoing prospective, population-based study of CAD
      and stroke with very high levels of clinical ascertainment, which allows detailed
      study of FH, and has already shown important new findings. Such data may help to
      formulate improved risk prediction tools and to inform future GWAS.

PMID- 22607506
TI  - Efficacy of folic acid supplementation in stroke prevention: new insight from a
      meta-analysis.
AB  - AIMS:   There are growing data and a continuing controversy over the efficacy of
      folic acid supplementation in stroke prevention. We conducted a meta-analysis
      based on relevant, up-to-date published randomised trials to further examine this
      issue. METHODS:   Relative risk (RR) was used to measure the effect of folic acid
      supplementation on risk of stroke with a fixed-effects model. RESULTS:   Overall,
      folic acid supplementation reduced the risk of stroke by 8% (n = 55,764; RR:
      0.92; 95% CI: 0.86-1.00, p = 0.038). In the 10 trials with no or partial folic
      acid fortification (n = 43,426), the risk of stroke was reduced by 11% (0.89;
      0.82-0.97, p = 0.010). Within these trials, a greater beneficial effect was
      observed among trials with a lower percent use of statins [<= 80% (median); 0.77;
      0.64-0.92, p = 0.005], and a meta-regression analysis also suggested a positive
      dose-response relationship between percent use of statins and log-RR for stroke
      associated with folic acid supplementation (p = 0.013). A daily dose of 0.4-0.8mg
      folic acid appeared to be adequate for stroke prevention in comparison with
      larger doses. In the remaining five trials conducted in populations with folic
      acid fortification (n = 12,338), folic acid supplementation had no effect on
      stroke risk (1.03; 0.88-1.21, 0.69). CONCLUSIONS:   Our analysis indicated that
      folic acid supplementation is effective in stroke prevention in populations with
      no or partial folic acid fortification. In addition, a greater beneficial effect
      was observed among trials with a lower percent use of statins. Our findings
      underscore the importance of identifying target populations that can particularly
      benefit from folic acid therapy.

PMID- 22607507
TI  - Aortic valve calcification - a commonly observed but frequently ignored finding
      during CT scanning of the chest.
AB  - AIM: To describe the frequency and severity of Aortic valve calcification (AVC)
      in an unselected cohort of patients undergoing chest CT scanning and to assess
      the frequency with which AVC was being reported in the radiology reports. METHODS
      AND RESULTS: Consecutive CT scan images of the chest and the radiological reports
      (December 2009 to May 2010) were reviewed at the district general hospital (DGH).
      AVC on CT scan was visually graded on a scale ranging from 0 to IV (0 = no
      calcification, IV = severe calcification). Total of 416 (232 male; 184 female) CT
      chest scans [Contrast enhanced 302 (72%), unenhanced 114 (28%)] were reviewed.
      Mean age was 70.55 +/- 11.48 years. AVC in CT scans was identified in 95 of the
      416 patients (22.83%). AVC classification was as follows: Grade I: 60 (63.15%),
      Grade II: 22 (23.15%), Grade III: 9 (9.47%), Grade IV: 4 (4.21%). Only one CT
      report mentioned AVC. Only 31 of 95 AVC had Transthoracic echocardiogram (TTE).
      The interval time between CT scan and TTE was variable. CONCLUSION:   Aortic
      valve calcification in CT chest scans is a common finding and studies have shown
      that it is strongly related to the presence and severity of aortic valve disease.
      As CT scans are considered as a valuable additional screening tool for detection
      of aortic stenosis, AVC should always be commented upon in the radiology reports.
      Furthermore, patients with at least Grade III and IV AVC should be sent for TTE.

PMID- 22607508
TI  - Advances in spontaneous intracerebral haemorrhage.
AB  - OBJECTIVES:   To assess the evidence and available literature on the clinical,
      pathogenetic, prognostic and therapeutic aspects of intracerebral haemorrhage.
      METHODS:   The most important manuscripts and reviews on the subject were
      considered. Information was collected from Medline, Embase & National Library of
      Medicine over the last 40 years up to Oct 2011. The bibliographies of relevant
      articles were searched for additional references. The most up to date and
      randomised trials were given preference. Clinical guidelines including AHA/ASA,
      Royal college of Physicians, NICE, Scottish Intercollegiate guidelines and
      several others were taken into consideration. FINDINGS:   There are numerous
      advances in the understanding of the pathogenesis and management, but hardly any
      change in the overall mortality in the last few decades. There is a poor
      understanding of the results of surgical trials that has resulted in a large drop
      in surgical intervention since 2007. INTERPRETATIONS AND IMPLICATIONS:  Advances
      in neuroimaging and neurophysiology have improved our understanding of the
      mechanisms of neuronal injury and existence of perihaematomal 'tissue at risk'.
      Numerous new therapeutic targets have been identified. There is a lot of
      misunderstanding of the results of the newer surgical trials which need to be
      clarified. The importance of cerebral amyloid angiopathy and microbleeds in older
      patients is increasingly recognised. Control of hypertension is the most
      important public health measure. Stroke units provide the best outcomes for the
      patients.

PMID- 22607509
TI  - Lack of radiation awareness among referrers: implications and possible solutions.
AB  - AIM: In the recent years, there has been a substantial increase in the use of
      ionising radiation investigations where it is known that this is associated with
      adverse effects most notably, risk of cancer. In the UK, it is estimated that 700
      new cancer cases/year will develop as a result of medical radiation. According to
      radiation regulations, all referrers should have awareness of the relevant
      radiation doses. With these facts in mind, the author wanted to assess the
      referrers' knowledge of radiation-induced cancer risk and radiation doses
      received by patients. METHODS:   Referrers from three hospitals took part in a
      questionnaire. An introduction about natural radiation & radiation risks was
      provided. The referrers were asked to (i) rank different radiological
      investigations from lowest to highest radiation dose, (ii) estimate the
      equivalent doses of radiation in chest X-ray (CXR) numbers and (iii) give an
      estimation of cancer risk upon performing them. RESULTS:   After receiving 100
      different responses, the online survey was deactivated. A total of 37% of all
      respondents ranked the radiological investigations correctly, 15% thought that
      Ultrasound and magnetic resonance imaging utilise ionising radiation. Eleven per
      cent also thought that radionuclide studies do not involve ionising radiation. A
      total of 82% and 50% correctly estimated the risk of cancer upon performing CXR
      and abdomen computed tomography respectively. CONCLUSION: A large proportion of
      the referrers underestimated the doses and risks involved, this lack of awareness
      of radiation risk has serious implications on patients, and maybe applied
      throughout the UK, if not globally. Possible solutions have also been discussed.

PMID- 22607510
TI  - Proton pump inhibitors: are they overutilised in clinical practice and do they
      pose significant risk?
AB  - Proton pump inhibitors are highly effective acid suppressants with decades of use
      highlighting positive outcomes in millions of patients worldwide, and they offer
      minimal risk of adverse events. PPIs are considered overutilised when prescribed
      without an appropriate indication, when patients are left on them 'indefinitely'
      without appropriate indications and when they are continued after being utilised
      for most cases of hospital SUP. While several adverse outcomes have been linked
      to PPI therapy, most data are from retrospective observational studies that may
      be subject to confounding and bias.

PMID- 22607511
TI  - Stress hyperglycaemia in patients with first myocardial infarction.
AB  - OBJECTIVE: To investigate the incidence of stress hyperglycaemia at first acute
      myocardial infarction (MI) with ST-segment elevation, occurrence of stress
      hyperglycaemia as a manifestation of previously undiagnosed abnormal glucose
      tolerance (AGT), and its relation to stress hormone levels. MATERIALS AND
      METHODS:   The population of this prospective cohort study consisted of 243
      patients. On admission glucose, adrenaline, noradrenaline and cortisol levels
      were measured. Patients without previously diagnosed diabetes (n = 204) underwent
      an oral glucose tolerance test on day 3 of hospitalisation and 3 months after
      discharge. RESULTS: Abnormal glucose tolerance at day 3 was observed in 92
      (45.1%) patients without a previous diagnosis of diabetes mellitus and resolved
      after 3 months in 46 (50.0%) patients (p < 0.0001). Stress hyperglycaemia,
      defined as admission glycaemia >= 11.1 mmol/l, affected 34 (14.0%) study
      participants: 28 (54.9%) patients with diabetes vs. 3 (8.8%) subjects with newly
      detected impaired glucose intolerance (p < 0.00001) and 1 (2.2%) person with AGT
      at day 3 (p < 0.000001). Multivariable analysis identified elevated glycated
      haemoglobin (HbA(1c) ; p < 0.0000001), anterior MI (p < 0.05) and high admission
      cortisol concentration (p < 0.001), but not catecholamines, as independent
      predictors of stress hyperglycaemia. The receiver operating characteristic curve
      analysis revealed the optimal cut-off values of 8.2% for HbA(1c) and 47.7 MUg/dl
      for admission cortisol with very good and sufficient diagnostic accuracies
      respectively. CONCLUSIONS:   Newly detected AGT in patients with a first MI is
      transient in 50% of cases. Stress hyperglycaemia is a common finding in patients
      with a first MI with ST-segment elevation and diabetes mellitus, but is rarely
      observed in individuals with impaired glucose tolerance or transient AGT
      diagnosed during the acute phase of MI. The risk factors of stress hyperglycaemia
      occurrence include elevated HbA(1c) , anterior MI and high admission cortisol
      concentration.

PMID- 22607513
TI  - Current trends in carotid surgery in England.

PMID- 22607512
TI  - Long-term effects of thyroid fine-needle biopsy on the thyroid-related
      biochemical parameters.
AB  - AIMS:   Thyroid fine-needle biopsy (FNB) is a simple, reliable, inexpensive and
      generally safe diagnostic procedure in the management of thyroid nodules. FNB may
      trigger biochemical alterations through destruction of thyroid follicles. We
      aimed to investigate long-term post-FNB alterations in serum thyroid-related
      parameters. METHODS:   One hundred and ten consecutive patients with thyroid
      nodular disease were subjected to FNB. Thyroid stimulating hormone (TSH), free
      thyroxine (FT4) and free triiodothyronine (FT3), thyroglobulin (Tg),
      thyroglobulin autoantibodies (anti-Tg), thyroid-peroxidase autoantibodies (anti
      TPO) were measured in all subjects at baseline, 10 days, 2 and 6 months.
      Subsequently, patients were divided into subgroups according to the technique of
      FNB, the presence of disease characteristics as thyroid autoimmunity (Hashimoto's
      thyroiditis), goitre, singularity-maximum diameter-blood pattern of the nodule(
      s), the number of passes and the administration of L-thyroxine (LT4). RESULTS: A
      significant increase in Tg, anti-Tg and FT3 levels was observed. These
      alterations were more prominent within patients with dominant nodule's maximum
      diameter >= 2 cm or without Hashimoto's thyroiditis. Tg and anti-Tg levels were
      significantly increased only in patients not being on LT4. On the other hand, FNB
      technique did not affect any of the measured parameters. CONCLUSION: Our data
      suggest that FNB results in statistically significant but clinically
      insignificant increases in Tg, anti-Tg and FT3 levels, implying a thyroid trauma
      of some level, more likely to happen in patients with larger nodules. The FNB
      technique used has no effect on the thyroid-related biochemical parameters.

PMID- 22607514
TI  - Mimicking adhesive functionalities of blood platelets using ligand-decorated
      liposomes.
AB  - Platelet transfusion is used for treating a variety of bleeding complications.
      Natural platelet-based transfusion products have very short storage life (3-7
      days) and high risks of biological contamination and side effects. Consequently,
      there is significant clinical interest in synthetic platelet-mimetic constructs
      that can promote hemostasis, while allowing convenient large-scale production,
      easy portability, long storage life, and minimal biological risks. To this end,
      research efforts are being directed toward particles that can amplify aggregation
      of activated platelets or can mimic platelet's ability to undergo adhesion to
      various vascular matrix proteins. Here, we report on a synthetic construct design
      that combines the mimicry of platelet's shear-dependent adhesion to vWF and shear
      independent adhesion to collagen under flow, on a single particle. For this, we
      have used 150-nm-diameter liposomes as model particles and have decorated their
      surface simultaneously with vWF-binding and collagen-binding recombinant protein
      fragments or synthetic peptide motifs. We demonstrate in vitro that these surface
      modified liposomes are able to adhere onto vWF surfaces in a shear-dependent
      fashion and onto collagen surfaces in a shear-independent fashion under flow.
      Moreover, when the vWF-binding and the collagen-binding were integrated on a
      single liposomal platform, the resultant heteromultivalent liposomes showed
      significantly enhanced adhesion to a vWF/collagen mixed surface compared to
      liposomes bearing vWF-binding or collagen-binding ligands only, as long as the
      ligand motifs did not spatially interfere with each other. Altogether, our
      results establish the feasibility of efficiently mimicking platelet's dual
      adhesion mechanisms on synthetic particles. 

PMID- 22607515
TI  - OmicsVis: an interactive tool for visually analyzing metabolomics data.
AB  - When analyzing metabolomics data, cancer care researchers are searching for
      differences between known healthy samples and unhealthy samples. By analyzing and
      understanding these differences, researchers hope to identify cancer biomarkers.
      Due to the size and complexity of the data produced, however, analysis can still
      be very slow and time consuming. This is further complicated by the fact that
      datasets obtained will exhibit incidental differences in intensity and retention
      time, not related to actual chemical differences in the samples being evaluated.
      Additionally, automated tools to correct these errors do not always produce
      reliable results. This work presents a new analytics system that enables
      interactive comparative visualization and analytics of metabolomics data obtained
      by two-dimensional gas chromatography-mass spectrometry (GC * GC-MS). The key
      features of this system are the ability to produce visualizations of multiple GC
      * GC-MS data sets, and to explore those data sets interactively, allowing a user
      to discover differences and features in real time. The system provides
      statistical support in the form of difference, standard deviation, and kernel
      density estimation calculations to aid users in identifying meaningful
      differences between samples. These are combined with novel transfer functions and
      multiform, linked visualizations in order to provide researchers with a powerful
      new tool for GC * GC-MS exploration and bio-marker discovery.

PMID- 22607517
TI  - The German fibromyalgia consumer reports - a cross-sectional survey.
AB  - BACKGROUND: Consumer surveys provide information on effectiveness and side
      effects of medical interventions in routine clinical care. A report of
      fibromyalgia syndrome (FMS) consumers has not been carried out in Europe.
      METHODS: The study was carried out from November 2010 to April 2011. Participants
      diagnosed with FMS rated the effectiveness and side effects of pharmacological
      and non-pharmacological FMS interventions on a 0 to 10 scale, with 10 being most
      efficacious (harmful). The questionnaire was distributed by the German League for
      people with Arthritis and Rheumatism and the German Fibromyalgia Association to
      their members and to all consecutive FMS patients of nine clinical centers of
      different levels of care. RESULTS: 1661 questionnaires (95% women, mean age 54
      years, mean duration since FMS diagnosis 6.8 years) were analysed. The most
      frequently used therapies were self-management strategies, prescription pain
      medication and aerobic exercise. The highest average effectiveness was attributed
      to whole body and local warmth therapies, thermal bathes, FMS education and
      resting. The highest average side effects were attributed to strong opioids,
      local cold therapy, gamma-amino-butyric acid analogues (pregabalin and
      gabapentin), tramadol and opioid transdermal systems. CONCLUSION: The German
      fibromyalgia consumer reports highlight the importance of non-pharmcological
      therapies in the long-term management of FMS, and challenges the strong
      recommendations for drug therapies given by FMS-guidelines.

PMID- 22607518
TI  - Relationship between behavioral and psychological symptoms of dementia and oral
      health status in the elderly with vascular dementia.
AB  - OBJECTIVES: The aim of this study was to clarify the relationship between
      behavioral and psychological symptoms of dementia (BPSD) and oral status in the
      elderly with vascular dementia. BACKGROUND: There have been some reports of a
      relationship between disease symptoms and oral status in the elderly with
      Alzheimer's disease, but few reports have been conducted in the elderly with
      vascular dementia. Until now, the relationship between BPSD and oral status has
      been unknown. MATERIALS AND METHODS: An investigation was conducted concerning
      BPSD and oral status among 57 subjects with vascular dementia (mean age, 85.7 +/-
      5.5 years). The wearing of dentures and oral activities of daily living (oral
      ADL) were examined. RESULTS: Subjects with activity disturbances and those with
      aggressiveness had significantly lower rates of denture wearing than those
      without these two symptoms (p < 0.05). Significantly lower oral ADL scores were
      obtained from subjects with delusional ideas, hallucinations, activity
      disturbances and diurnal rhythm disturbances (p < 0.05), as well as those with
      affective disturbances (p< 0.01). CONCLUSION: This study indicated a relationship
      between BPSD and the wearing of dentures in the elderly with vascular dementia.
      The study also demonstrated relationships between BPSD and oral ADL.

PMID- 22607519
TI  - Macrophage activation syndrome in a patient with pulmonary inflammatory
      myofibroblastic tumour.
AB  - We describe for the first time a case of macrophage activation syndrome (MAS) in
      a patient with a history of inflammatory myofibroblastic tumour (inflammatory
      pseudotumour, IPT) of the lung and thoracic spine. The patient was admitted to
      the intensive care unit with a history of prolonged remitting fever,
      hepatosplenomegaly, bilaterally enlarged thoracic lymph nodes and an acute severe
      inflammatory response syndrome (SIRS). Up-regulated cytokine production (e.g. IL
      1beta and IL-6), increased levels of ferritin and circulating soluble interleukin
      2 receptor (sIL-2R, sCD25) led to the differential diagnosis of MAS. Bone marrow
      aspiration, the main tool for a definite diagnosis, revealed macrophages
      phagocytosing haematopoietic cells. Immunosuppressive therapy with
      corticosteroids and cyclosporine was an effective treatment in this patient.

PMID- 22607520
TI  - Single-incision robotic-assisted living donor nephrectomy: case report and
      description of surgical technique.
AB  - The introduction of laparoscopic surgery, and more recently of robotics, has
      increased the number of living donor kidney transplants. This approach has
      already improved living donor acceptance rates. Even newer developments in the
      field have now been introduced with the purpose of further reducing postoperative
      pain and length of hospital stay, while offering better cosmetic results. In
      particular, single-incision surgery has gained popularity by improving the well
      known benefits of minimally invasive surgery. In this case report, we present the
      first single-incision robotic-assisted living donor nephrectomy.

PMID- 22607521
TI  - Statistical methodology for the detection of small changes in distances by EXAFS:
      application to the antimalarial ruthenoquine.
AB  - Antimalarial compounds ruthenoquine and methylruthenoquine were studied by X-ray
      absorption spectroscopy both in solid state and in solution, in normal (aqueous
      or CH(2)Cl(2) solutions) and oxidative (aqueous solution with H(2)O(2), either
      equimolar or in large excess) conditions, to detect small changes in the
      coordination sphere of the ruthenium atom. Since changes in the EXAFS spectra of
      these compounds are quite subtle, a complete procedure was developed to assess
      the different sources of uncertainties in fitted structural parameters, including
      the use of multivariate statistic methods for simultaneous comparison of edge
      energy correction DeltaE(0) and distances, which can take into account the very
      strong correlation between these two parameters. Factors limiting the precision
      of distance determination depend on the recording mode. In transmission mode, the
      main source of uncertainty is the data reduction process, whereas in fluorescence
      mode, experimental noise is the main source of variability in the fitted
      parameters. However, it was shown that the effects of data reduction are
      systematic and almost identical for all compounds; hence, they can be ignored
      when comparing distances. Consequently, for both fluorescence and transmission
      recorded spectra, experimental noise is the limiting factor for distance
      comparisons, which leads to the use of statistical methods for comparing
      distances. Univariate methods, focusing on the distance only, are shown to be
      less powerful in detecting changes in distances than bivariate methods making a
      simultaneous comparison of DeltaE(0) and distances. This bivariate comparison can
      be done either by using the Hotelling's T(2) test or by using a graphical
      comparison of Monte Carlo simulation results. We have shown that using these
      methods allows for the detection of very subtle changes in distances. When
      applied to ruthenoquine compounds, it suggests that the implication of the
      nonbinding doublet of the aminoquine nitrogen in either protonation or
      methylation enhances the tilt of the two cyclopentadienyls. It also suggests that
      ruthenoquine and methylruthenoquine are, at least partially, oxidized in the
      presence of H(2)O(2), with a small decrease in the Ru-C bond length and increase
      in the edge energy.

PMID- 22607516
TI  - Definition of advanced age in HIV infection: looking for an age cut-off.
AB  - The age of 50 has been considered as a cut-off to discriminate older subjects
      within HIV-infected people according to the Centers for Disease Control and
      Prevention (CDC). However, the International AIDS Society (IAS) mentions 60 years
      of age and the Department of Health and Human Services (DHHS) makes no
      consideration. We aimed to establish an age cut-off that could differentiate
      response to highly active antiretroviral therapy (HAART) and, therefore, help to
      define advanced age in HIV-infected patients. CoRIS is an open, prospective,
      multicenter cohort of HIV adults naive to HAART at entry (January 2004 to October
      2009). Survival, immunological response (IR) (CD4 increase of more than 100
      cell/ml), and virological response (VR) (HIV RNA less than 50 copies/ml) were
      compared among 5-year age intervals at start of HAART using Cox proportional
      hazards models, stratified by hospital and adjusted for potential confounders.
      Among 5514 patients, 2726 began HAART. During follow-up, 2164 (79.4%) patients
      experienced an IR, 1686 (61.8%) a VR, and 54 (1.9%) died. Compared with patients
      aged <25 years at start of HAART, those aged 50-54, 55-59, 60-64, 65-59, and 70
      or older were 32% (aHR: 0.68, 95% CI: 0.52-0.87), 29% (aHR: 0.71, 95% CI: 0.53
      0.96), 34% (aHR: 0.66, 95% CI: 0.46-0.95), 39% (aHR: 0.61, 95% CI: 0.37-1.00),
      and 43% (aHR: 0.57, 95% CI: 0.31-1.04) less likely to experience an IR. The VR
      was similar across all age groups. Finally, patients aged 50-59 showed a 3-fold
      increase (aHR: 3.58; 95% CI: 1.07-11.99) in their risk of death compared to those
      aged <30 years. In HIV infection, patients aged >=50 years have a poorer
      immunological response to HAART and a poorer survival. This age could be used to
      define medically advanced age in HIV-infected people.

PMID- 22607522
TI  - Rate of gestational weight gain, pre-pregnancy body mass index and preterm birth
      subtypes: a retrospective cohort study from Peru.
AB  - OBJECTIVE: To examine the shape (functional form) of the association between the
      rate of gestational weight gain, pre-pregnancy body mass index (BMI), and preterm
      birth and its subtypes. DESIGN:   Retrospective cohort study. SETTING:   National
      reference obstetric centre in Lima, Peru. POPULATION:   Pregnant women who
      delivered singleton babies during the period 2006-2009, resident in Lima, and
      beginning prenatal care at <= 12 weeks of gestation (n=8964). METHODS:   Data
      were collected from the centre database. The main analyses consisted of logistic
      regression with fractional polynomial modelling. MAIN OUTCOME MEASURES:   Preterm
      birth and its subtypes. RESULTS:   Preterm birth occurred in 12.2% of women,
      being mostly idiopathic (85.7%). The rate of gestational weight gain was
      independently associated with preterm birth, and the shape of this association
      varied by pre-pregnancy BMI. In women who were underweight, the association was
      linear (per 0.1 kg/week increase) and protective (OR 0.88; 95% CI 0.82-1.00). In
      women of normal weight or who were overweight, the association was U-shaped: the
      odds of delivering preterm increased exponentially with rates <0.10 or >0.66
      kg/week, and <0.04 or >0.50 kg/week, respectively. In women who were obese, the
      association was linear, but non-significant (OR 1.01; 95% CI 0.95-1.06). The
      association described for preterm birth closely resembled that of idiopathic
      preterm birth, although the latter was stronger. The rate of gestational weight
      gain was not associated with indicated preterm birth or preterm prelabour rupture
      of membranes. CONCLUSIONS:   In Peruvian pregnant women starting prenatal care at
      <= 12 weeks of gestation, the rate of gestational weight gain is independently
      associated with preterm birth, mainly because of its association with idiopathic
      preterm birth, and the shape of both associations varies by pre-pregnancy BMI.

PMID- 22607523
TI  - Genetic diversity and population genetic analysis of bovine MHC class II DRB3.2
      locus in three Bos indicus cattle breeds of Southern India.
AB  - The present study was performed to evaluate the genetic polymorphism of BoLA
      DRB3.2 locus in Malnad Gidda, Hallikar and Ongole South Indian Bos indicus cattle
      breeds, employing the PCR-RFLP technique. In Malnad Gidda population, 37 BoLA
      DRB3.2 alleles were detected, including one novel allele DRB3*2503 (GenBank:
      HM031389) that was observed in the frequency of 1.87%. In Hallikar and Ongole
      populations, 29 and 21 BoLA-DRB3.2 alleles were identified, respectively. The
      frequencies of the most common BoLA-DRB3.2 alleles (with allele frequency > 5%),
      in Malnad Gidda population, were DRB3.2*15 (10.30%), DRB3*5702 (9.35%), DRB3.2*16
      (8.41%), DRB3.2*23 (7.01%) and DRB3.2*09 (5.61%). In Hallikar population, the
      most common alleles were DRB3.2*11 (13.00%), DRB3.2*44 (11.60%), DRB3.2*31
      (10.30%), DRB3.2*28 (5.48%) and DRB3.2*51 (5.48%). The most common alleles in
      Ongole population were DRB3.2*15 (22.50%), DRB3.2*06 (20.00%), DRB3.2*13
      (13.30%), DRB3.2*12 (9.17%) and DRB3.2*23 (7.50%). A high degree of
      heterozygosity observed in Malnad Gidda (H(O) = 0.934, H(E) = 0.955), Hallikar
      (H(O) = 0.931, H(E) = 0.943) and Ongole (H(O) = 0.800, H(E) = 0.878) populations,
      along with F(IS) values close to F(IS) zero (Malnad Gidda: F(IS) = 0.0221,
      Hallikar: F(IS) = 0.0127 and Ongole: F(IS) = 0.0903), yielded nonsignificant P
      values with respect to Hardy-Weinberg equilibrium probabilities revealing, no
      perceptible inbreeding, greater genetic diversity and characteristic population
      structure being preserved in the three studied cattle populations. The
      phylogenetic tree constructed based on the frequencies of BoLA-DRB3.2 alleles
      observed in 10 Bos indicus and Bos taurus cattle breeds revealed distinct
      clustering of specific Bos indicus cattle breeds, along with unique genetic
      differentiation observed among them. The results of this study demonstrated that
      the BoLA-DRB3.2 is a highly polymorphic locus, with significant breed-specific
      genetic diversities being present amongst the three studied cattle breeds. The
      population genetics and phylogenetic analysis have revealed pivotal information
      about the population structure and importance of the presently studied three Bos
      indicus cattle breeds as unique animal genetic resources, which have to be
      conserved for maintaining native cattle genetic diversity.

PMID- 22607524
TI  - Emission characteristics of heavy metals and their behavior during coking
      processes.
AB  - Besides organic pollutants, coke production generates emissions of toxic heavy
      metals. However, intensive studies on heavy metal emissions from the coking
      industry are still very scarce. The current work focuses on assessing the
      emission characteristics of heavy metals and their behavior during coking.
      Simultaneous sampling of coal, coke, residues from air pollution control devices
      (APCD), effluent from coke quenching, and fly ash from different processes before
      and after APCD has been performed. The total heavy metal concentration in the
      flue gas from coke pushing (CP) was significantly higher than that from coal
      charging (CC) and combustion of coke oven gases (CG). Emission factors of heavy
      metals for CP and CC were 378.692 and 42.783 MUg/kg, respectively. During coking,
      the heavy metals that were contained in the feedstock coal showed different
      partitioning patterns. For example, Cu, Zn, As, Pb, and Cr were obviously
      concentrated in the inlet fly ash compared to the coke; among these metals Cu,
      As, and Cr were concentrated in the outlet fly ash, whereas Zn and Pb were
      distributed equally between the outlet fly ash and APCD residue. Ni, Co, Cd, Fe,
      and V were partitioned equally between the inlet fly ash and the coke.
      Understanding the behavior of heavy metals during coking processes is helpful for
      the effective control of these heavy metals and the assessment of the potential
      impact of their emissions on the environment.

PMID- 22607526
TI  - Mechanism of Cd and Cu action on the tonoplast proton pumps in cucumber roots.
AB  - The effect of Cd and Cu on the tonoplast proton pumps, V-ATPase (EC 3.6.3.14) and
      V-PPase (EC 3.6.1.1) was investigated in cucumber roots subjected to 10 uM metals
      for 3 and 6 days. Both hydrolytic and transporting activities of V-ATPase as well
      as V-PPase increased under copper stress. In contrast, all activities examined
      were inhibited after the exposure of plants to cadmium. Cd and Cu changed the
      efficiency of coupling between proton transport and ATP hydrolysis whereas H(+)
      /PP(i)  stoichiometry was not modified. Pre-incubation of control tonoplast
      vesicles with copper caused the stimulation of V-ATPase as well as V-PPase,
      indicating direct activation by Cu ions. Pre-treatment with cadmium had no
      significant effect on the activities of both enzymes. The gene expression and
      western blot analyses showed that observed modifications in enzyme activities
      were not related to the changes in the transcript levels of genes encoding V
      ATPase subunit A and c, and V-PPase or in amounts of enzyme proteins. Moreover,
      the addition of reduced or oxidized glutathione (GSH and GSSG) to the reaction
      medium containing tonoplast vesicles isolated from stressed roots did not change
      the activity level of either enzyme when compared with the controls, suggesting
      that heavy metal-induced modifications are not simple reversible redox
      modulations.

PMID- 22607525
TI  - Persistent frequent attenders in primary care: costs, reasons for attendance,
      organisation of care and potential for cognitive behavioural therapeutic
      intervention.
AB  - BACKGROUND: The top 3% of frequent attendance in primary care is associated with
      15% of all appointments in primary care, a fivefold increase in hospital
      expenditure, and more mental disorder and functional somatic symptoms compared to
      normal attendance. Although often temporary if these rates of attendance last
      more than two years, they may become persistent (persistent frequent or regular
      attendance). However, there is no long-term study of the economic impact or
      clinical characteristics of regular attendance in primary care. Cognitive
      behaviour formulation and treatment (CBT) for regular attendance as a motivated
      behaviour may offer an understanding of the development, maintenance and
      treatment of regular attendance in the context of their health problems,
      cognitive processes and social context. METHODS/DESIGN: A case control design
      will compare the clinical characteristics, patterns of health care use and
      economic costs over the last 10 years of 100 regular attenders (>=30 appointments
      with general practitioner [GP] over 2 years) with 100 normal attenders (6-22
      appointments with GP over 2 years), from purposefully selected primary care
      practices with differing organisation of care and patient demographics.
      Qualitative interviews with regular attending patients and practice staff will
      explore patient barriers, drivers and experiences of consultation, and
      organisation of care by practices with its challenges. Cognitive behaviour
      formulation analysed thematically will explore the development, maintenance and
      therapeutic opportunities for management in regular attenders. The feasibility,
      acceptability and utility of CBT for regular attendance will be examined.
      DISCUSSION: The health care costs, clinical needs, patient motivation for
      consultation and organisation of care for persistent frequent or regular
      attendance in primary care will be explored to develop training and policies for
      service providers. CBT for regular attendance will be piloted with a view to
      developing this approach as part of a multifaceted intervention.

PMID- 22607527
TI  - Structural characterization of wheat straw lignin as revealed by analytical
      pyrolysis, 2D-NMR, and reductive cleavage methods.
AB  - The structure of the lignin in wheat straw has been investigated by a combination
      of analytical pyrolysis, 2D-NMR, and derivatization followed by reductive
      cleavage (DFRC). It is a p-hydroxyphenyl-guaiacyl-syringyl lignin (with an H:G:S
      ratio of 6:64:30) associated with p-coumarates and ferulates. 2D-NMR indicated
      that the main substructures present are beta-O-4'-ethers (~~75%), followed by
      phenylcoumarans (~11%), with lower amounts of other typical units. A major new
      finding is that the flavone tricin is apparently incorporated into the lignins.
      NMR and DFRC indicated that the lignin is partially acylated (~10%) at the gamma
      carbon, predominantly with acetates that preferentially acylate guaiacyl (12%)
      rather than syringyl (1%) units; in dicots, acetylation is predominantly on
      syringyl units. p-Coumarate esters were barely detectable (<1%) on monomer
      conjugates released by selectively cleaving beta-ethers in DFRC, indicating that
      they might be preferentially involved in condensed or terminal structures.

PMID- 22607528
TI  - Annular erythematous plaques in a patient with asthma.

PMID- 22607530
TI  - Concurrent onabotulinumtoxinA treatment of cervical dystonia and concomitant
      migraine.
AB  - OBJECTIVE: The objective of this study was to assess the clinical benefits of
      onabotulinumtoxinA (BOTOX(r)) treatment on the symptoms of cervical dystonia and
      the frequency, severity, and associated symptoms of migraine in patients with
      cervical dystonia and concurrent migraine. BACKGROUND: Botulinum toxin is
      established as first-line treatment of cervical dystonia. Recent clinical trials
      have shown onabotulinumtoxinA to be an effective prophylactic therapy for
      patients with chronic migraine, and onabotulinumtoxinA has been approved for use
      in this patient population by the Food and Drug Administration. Patients with
      headache associated with cervical dystonia have been identified as a specific
      subpopulation of patients in whom botulinum toxin treatment may be effective for
      controlling the symptoms of both conditions. METHODS: An open-label pilot study
      was conducted for 7.5 months in patients at least 18 years old with primary
      cervical dystonia of moderate severity (baseline rating of at least 20 on the
      Toronto Western Spasmodic Torticollis Rating Scale) complicated by migraine
      headache meeting the International Classification of Headache Disorders-II
      criteria for migraines with or without aura. Each patient received 2 cycles of
      treatment at Visit 3 (baseline) and Visit 6 (Day 90). For cervical dystonia, each
      patient was injected with a maximum of 175 units. At the same visit, a maximum of
      125 units was also injected for migraine using a fixed-site, fixed-dose injection
      paradigm, with additional cervical dystonia injection-site treatment to a maximum
      dose of 300 units. Patients were assessed following onabotulinumtoxinA injection
      and at follow-up on Visit 4 (Day 30), Visit 5 (Day 60), Visit 6 (Day 90), and at
      Visits 7, 8, and 9 (Days 120, 150, and 180). The primary outcome measures for
      this study were change in Toronto Western Spasmodic Torticollis Rating Scale
      total score for cervical dystonia and frequency of headache episodes per 28-day
      period. Migraine episodes were defined as at least 4 hours of sustained pain with
      no upper limit. An episode was considered new if the patient was pain free for at
      least 24 hours. Secondary study end points included number of headache days per
      month, headache intensity, headache disability (assessed using Headache Impact
      Test-6 and the Migraine Disability Assessment score scales), acute headache
      medication use, resource utilization, and allodynia pain. Adverse events were
      reported. RESULTS: A total of 25 patients (24 women, mean age 50.5 years; mean
      age of disease onset 21.9 years) were enrolled in the study. Patients experienced
      improvement in cervical dystonia symptoms with significant reductions from
      baseline in Toronto Western Spasmodic Torticollis Rating Scale scores at 30, 60,
      90, 120, 150, and 180 days (-9.84 +/- 8.49, -12.67 +/- 8.22, -13.63 +/- 7.27, 
      14.92 +/- 7.05, -14.76 +/- 6.97, -14.49 +/- 6.14, respectively, P < .0001 at all
      time points from a baseline of 31.03 +/- 3.61). Changes from baseline were
      assessed using the t-test. Reductions in the number of headache episodes from
      baseline on concurrent onabotulinumtoxinA treatment for coexistent chronic
      migraine did not attain significance. However, patients experienced significant
      reductions from baseline in the number of headache days at 90, 120, and 180 days
      (-3.39 +/- 6.78, P = .0289; -4.29 +/- 7.94, P = .0194; -4.38 +/- 7.99, P = .0178,
      respectively, from a baseline of 15.33 +/- 6.76). Changes from baseline were
      assessed using the t-test. The change from baseline in Headache Impact Test-6
      total scores was significant at 30, 60, 90, 150, and 180 days (3.21 +/- 4.14, P =
      .0009; -3.04 +/- 4.04, P = .0012; -2.41 +/- 2.79, P = .0006; -2.59 +/- 3.87, P =
      .0050; -3.09 +/- 3.80, respectively, from a baseline of 22.68 +/- 3.20). Changes
      from baseline were assessed using the t-test. The change from baseline in
      Migraine Disability Assessment was significant at 120, 150, and 180 days (-38.09
      +/- 47.87, P < .0001, Wilcoxon signed rank test; -16.91 +/- 62.69, P = .0358,
      Wilcoxon signed rank test; -23.73 +/- 40.57, P = .0122, t-test, respectively,
      from a baseline of 56.68 +/- 50.41). There were no serious adverse events or
      treatment-related discontinuations. CONCLUSIONS: Concurrent treatment with
      onabotulinumtoxinA is effective and well tolerated in controlling the symptoms of
      cervical dystonia complicated by concurrent migraine.

PMID- 22607529
TI  - Imaging of poly(alpha-hydroxy-ester) scaffolds with X-ray phase-contrast
      microcomputed tomography.
AB  - Porous scaffolds based on poly(alpha-hydroxy-esters) are under investigation in
      many tissue engineering applications. A biological response to these materials is
      driven, in part, by their three-dimensional (3D) structure. The ability to
      evaluate quantitatively the material structure in tissue-engineering applications
      is important for the continued development of these polymer-based approaches. X
      ray imaging techniques based on phase contrast (PC) have shown a tremendous
      promise for a number of biomedical applications owing to their ability to provide
      a contrast based on alternative X-ray properties (refraction and scatter) in
      addition to X-ray absorption. In this research, poly(alpha-hydroxy-ester)
      scaffolds were synthesized and imaged by X-ray PC microcomputed tomography. The
      3D images depicting the X-ray attenuation and phase-shifting properties were
      reconstructed from the measurement data. The scaffold structure could be imaged
      by X-ray PC in both cell culture conditions and within the tissue. The 3D images
      allowed for quantification of scaffold properties and automatic segmentation of
      scaffolds from the surrounding hard and soft tissues. These results provide
      evidence of the significant potential of techniques based on X-ray PC for imaging
      polymer scaffolds.

PMID- 22607531
TI  - Expression and morphology of enterotoxigenic  Escherichia coli  surface antigen
      CS31A in E. coli K12 and  Vibrio cholerae.
AB  - Enterotoxigenic  Escherichia coli  (ETEC) is known as a worldwide cause of
      diarrheal disease. The pathogenesis involves the attachment of the microorganisms
      to the mucosa and the production of enterotoxins. Surface expression of CS31A
      fimbriae was assessed by Western blots, dot blots, immunofluorescence, and
      electron microscopy using negative staining and immunogold labeling. These
      investigations revealed significant differences in both the morphology of the
      wild-type and recombinant strains and the antigen exposure of CS31A in the wild
      type and recombinant strains. In the wild-type ETEC strain, expression of CS31A
      was subject to phase variation. The recombinant E. coli strain produced CS31A but
      was prone to epitope shedding. In  Vibrio cholerae  vaccine strain CVD 103-HgR,
      the recombinant CS31A antigen was expressed but was only found intracellularly.
      Thus, E. coli strains seem to lend themselves better to the development of
      recombinant vaccines expressing ETEC-specific antigens at the cell's surface than
      strains from other orders or genera such as V. cholerae.

PMID- 22607532
TI  - Continuous electrochemical monitoring of extracellular lactate production from
      neonatal rat cardiomyocytes following myocardial hypoxia.
AB  - Continuous monitoring of lactate production from cardiomyocytes is of great
      physiological and pathological importance since the level of lactate in
      extracellular fluid is closely associated with myocardial energy metabolism with
      implication in the diagnosis and therapeutics of myocardial hypoxia and ischemia.
      This study demonstrates an electrochemical approach to continuous monitoring of
      lactate production from neonatal rat cardiomyocytes following myocardial hypoxia
      with a dehydrogenase-based electrochemical biosensor and a negative pressure
      driven culture sampling. To eliminate the effect of pH variation occurring
      following the cardiomyocyte hypoxia on the biosensor response and to supply
      nicotinamide adenine dinucleotide (NAD(+)) cofactor necessary for the enzymatic
      reaction of lactate dehydrogenase (LDH), artificial cerebrospinal fluid (aCSF)
      containing NAD(+) cofactor is externally perfused and mixed online with cell
      culture before the culture goes to the detector. The method exhibits a high
      selectivity against the electrochemically active species endogenously existing in
      the extracellular culture of cardiomyocytes and a high tolerance against the
      variation of pH following cardiomyocyte hypoxia. The dynamic linear range for
      lactate detection is from 0.20 to 10 mM (I (nA) = 25.6 C(Lactate) (mM) + 20.1,
      gamma = 0.996) with a detection limit of 0.16 mM (S/N = 3). The physiological
      level of the extracellular lactate of neonatal rat cardiomyocytes is determined
      to be 1.1 +/- 0.1 mM (n = 3) with the cell density of about 0.5 * 10(3)
      cells/mm(2). When the cardiomyocytes are subject to hypoxia induced with anoxic
      reagents, carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), the
      extracellular lactate increases to 255 +/- 30.3% (n = 3), relative to the
      physiological level, following 20 min of the hypoxia. This study essentially
      offers a new and effective electrochemical platform for investigating energy
      metabolism during cardiac physiological and pathological processes.

PMID- 22607534
TI  - Liposomal quercetin: evaluating drug delivery in vitro and biodistribution in
      vivo.
AB  - OBJECTIVE: The drug-loaded PEGylated nanomaterials have shown effective cell
      killing in vitro, but to the best of authors' knowledge there have been no
      reports of successful drug delivery in vitro and in vivo using polyethyleneglycol
      2000-distearoyl phosphatidyl ethanolamine (PEG2000-DSPE) nanomaterials loaded
      with unmodified drug molecules, such as quercetin (QUE). In this study, it
      remained an open question as to whether such formulations could prove effective
      in vitro and in vivo, and to study the distribution and clearance of PEG-DPSE
      ylated lipid-based quercetin nanoliposomes (PEG2000-DPSE-QUE-NLs) as delivery
      vehicles for the anticancer drug in vitro and in vivo. RESEARCH DESIGN AND
      METHODS: PEG-DPSE layers were attached to QUE-NLs, dispersed in aqueous media and
      characterized using TEM and HPLC/UV spectroscopy. Tumor cell killing efficacy was
      assessed in vitro using MTT and trypan blue exclusion assays, and the
      distribution and clearance pathways, as well as repeated administration in rats,
      were studied by HPLC spectroscopy. RESULTS: PEG2000-DPSE-QUE-NLs were efficiently
      dispersed in aqueous media compared with controls, and PEGylated (PEG2000-DPSE)
      NLs were found to be effective drug delivery vehicles when simply loaded with
      QUE. The plasma QUE concentration decreased significantly (p < 0.05) after
      repeated administration of PEG2000-DSPE liposomal QUE. There was a slight ABC
      phenomenon with the PEG2000-DSPE-modified QUE liposomes. CONCLUSION: The
      QUE/PEG2000-DPSE formulation was more effective than QUE in vitro on inhibiting
      the growth of glioma cancer cells. This work demonstrates that nanomaterials
      (PEG2000-DPSE) are effective drug delivery vehicles in vivo as tumor-targeted
      drug carriers.

PMID- 22607535
TI  - Recent advances in brain tumor-targeted nano-drug delivery systems.
AB  - INTRODUCTION: Brain tumors represent one of the most challenging and difficult
      areas in unmet medical needs. Fortunately, the past decade has seen momentous
      developments in brain tumor research in terms of brain tumor-targeted novel nano
      drug delivery systems with significant important superiority over conventional
      formulations with respect to decreased toxicity and improved
      pharmacokinetics/pharmacodynamics. AREA COVERED: This review first introduces the
      characteristics of the two major obstacles in brain-tumor targeted delivery,
      blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB), and then reviews
      recent advances in brain tumor-targeted novel nano-drug delivery systems
      according to their targeting strategies aimed at different stages of brain tumor
      development and growth. EXPERT OPINION: Based on continuously changing vascular
      characteristics of brain tumors at different development and growth stages, we
      propose the concept of 'whole-process targeting' for brain tumor for nano-drug
      delivery systems, referring to a series of overall targeted drug delivery
      strategies aimed at key points during the whole development of brain tumors.

PMID- 22607536
TI  - Peptic ulcer bleeding in patients with or without cirrhosis: different diseases
      but the same prognosis?
AB  - BACKGROUND: Physiopathology and prognosis of peptic ulcer bleeding (PUB) have
      never been described in cirrhotic patients. AIM: To assess risk factors and
      outcome of PUB in two groups of patients with PUB with or without cirrhosis.
      METHODS: We included prospectively all patients with PUB referred to our ICU of
      Hepatology and Gastroenterology between January 2008 and March 2011. All patients
      were treated according to international recommendations. Diagnosis of cirrhosis
      was based on clinical, biological and morphological exams. Aetiologies,
      characteristics and outcomes of PUB were compared in cirrhotic vs. noncirrhotic
      patients. RESULTS: A total of 203 patients with PUB were included prospectively.
      Twenty-nine patients had cirrhosis (group Cirr+), and 174 patients had no
      cirrhosis (group Cirr-). Demographic data were similar between the two groups
      except for age and alcohol consumption. Aetiology of cirrhosis was alcohol in 97%
      of cirrhotic patients. Characteristics of PUB were not different between the two
      groups. Ninety-three per cent of patients with cirrhosis had endoscopic portal
      hypertension. Aetiology of PUB was different between the group Cirr+ and Cirr-
      (Helicobacter pylori = 10.3% vs. 48.8%, P < 0.0001; NSAID's = 17.2% vs. 54.0%, P
      < 0.0001; idiopathic PUB = 79.3% vs. 23.8%, P < 0.0001). Outcome was comparable
      concerning re-bleeding (7.0% vs. 6.9%, P = 0.31), need for arterial embolisation
      (10.3 vs. 8.6%, P = 0.76), need for salvage surgery (0 vs. 1.7%, P = 0.31) and
      mortality (3.0% vs. 1.1%, P = 0.87). CONCLUSIONS: Physiopathology of PUB seems to
      be different in patients with cirrhosis. In cirrhotic patients, PUB occurs almost
      only in alcoholics. In our series, prognosis was similar to general population.
      PUB in cirrhosis might be related to portal hypertension and/or alcohol.

PMID- 22607537
TI  - Childhood brain tumours and use of mobile phones: comparison of a case-control
      study with incidence data.
AB  - The first case-control study on mobile phone use and brain tumour risk among
      children and adolescents (CEFALO study) has recently been published. In a
      commentary published in Environmental Health, Soderqvist and colleagues argued
      that CEFALO suggests an increased brain tumour risk in relation to wireless phone
      use. In this article, we respond and show why consistency checks of case-control
      study results with observed time trends of incidence rates are essential, given
      the well described limitations of case-control studies and the steep increase of
      mobile phone use among children and adolescents during the last decade. There is
      no plausible explanation of how a notably increased risk from use of wireless
      phones would correspond to the relatively stable incidence time trends for brain
      tumours among children and adolescents observed in the Nordic countries.
      Nevertheless, an increased risk restricted to heavy mobile phone use, to very
      early life exposure, or to rare subtypes of brain tumours may be compatible with
      stable incidence trends at this time and thus further monitoring of childhood
      brain tumour incidence rate time trends is warranted.

PMID- 22607538
TI  - In vitro fertilisation: perinatal risks and early childhood outcomes.

PMID- 22607542
TI  - 9-Mercaptodethiobiotin is generated as a ligand to the [2Fe-2S]+ cluster during
      the reaction catalyzed by biotin synthase from Escherichia coli.
AB  - Biotin synthase catalyzes formation of the thiophane ring through stepwise
      substitution of a sulfur atom for hydrogen atoms at the C9 and C6 positions of
      dethiobiotin. Biotin synthase is a radical S-adenosylmethionine (SAM) enzyme that
      reductively cleaves S-adenosylmethionine, generating 5'-deoxyadenosyl radicals
      that initially abstract a hydrogen atom from the C9 position of dethiobiotin. We
      have proposed that the resulting dethiobiotinyl radical is quenched by the MU
      sulfide of the nearby [2Fe-2S](2+) cluster, resulting in coupled formation of 9
      mercaptodethiobiotin and a reduced [2Fe-2S](+) cluster. This reduced FeS cluster
      is observed by electron paramagnetic resonance spectroscopy as a mixture of two
      orthorhombic spin systems. In the present work, we use isotopically labeled 9
      mercaptodethiobiotin and enzyme to probe the ligand environment of the [2Fe
      2S](+) cluster in this reaction intermediate. Hyperfine sublevel correlation
      spectroscopy (HYSCORE) spectra exhibit strong cross-peaks demonstrating strong
      isotropic coupling of the nuclear spin with the paramagnetic center. The
      hyperfine coupling constants are consistent with a structural model for the
      reaction intermediate in which 9-mercaptodethiobiotin is covalently coordinated
      to the remnant [2Fe-2S](+) cluster.

PMID- 22607543
TI  - Periodontal biomechanics: finite element simulations of closing stroke and power
      stroke in equine cheek teeth.
AB  - BACKGROUND: In equine dentistry periodontal diseases, especially periapical
      inflammation, are frequently occurring problems. Anachoresis is believed to be
      the most common cause for the development of such disorders. Nevertheless, there
      is still no substantiated explanation why settlement of pathogen microorganisms
      occurs in equine periodontal tissues. It is expected that excessive strains and
      stresses occurring in the periodontal ligament (PDL) during the horse's chewing
      cycle might be a predisposing factor. In this study this assumption was examined
      by finite element (FE) analyses on virtual 3-D models of equine maxillary and
      mandibular cheek teeth, established on the basis of MUCT datasets. Calculations
      were conducted both under conditions of closing and power stroke. RESULTS:
      Results showed a uniform distribution of low stresses and strain energy density
      (SED) during closing stroke, whereas during power stroke an occurrence of high
      stresses and SED could be observed in the PDL near the alveolar crest and in
      periapical regions. CONCLUSION: The concentration of forces during power stroke
      in these specific areas of the PDL may cause local tissue necrosis and
      inflammation and thus establish a suitable environment for the settlement of
      microorganisms.

PMID- 22607544
TI  - Survival after diagnosis of hepatocellular carcinoma and potential impact of
      treatment in a hepatitis B or C infected cohort.
AB  - AIM:   Little is known about the patterns of care and the impact of
      hepatocellular carcinoma (HCC) treatment on health outcomes at a population
      level. We conducted a population-based cohort study to examine HCC survival
      trends among people diagnosed with hepatitis B (HBV) or hepatitis C virus (HCV)
      infection, to determine predictors of receiving potentially curative therapy for
      HCC, and to examine the impact of HCC treatment on survival in New South Wales,
      Australia. METHODS:   The Kaplan-Meier method was used to estimate survival,
      logistic regression to determine predictors of potentially curative therapy and
      Cox proportional hazards models to determine the impact of HCC treatment on
      survival. Years of potential life lost (YPLL) were calculated. RESULTS:   During
      the period 1993-2007, 1081 cases of HCC were diagnosed. Median survival increased
      from 10.4 months during 1993-1997 to 18.4 months during 1998-2002, with no
      further improvement thereafter. Younger age at diagnosis (<65 years), being Asian
      born and having multiple comorbid conditions increased the odds of receiving
      curative therapy. The effect of HCC treatment on the risk of mortality was
      similar between the HBV- and HCV-related HCC groups. Tumor-specific therapies had
      adjusted hazard ratios ranging 0.06-0.25 and palliative/supportive therapy alone
      had adjusted hazard ratios ranging 0.76-1.08. The average YPLL per person was
      23.3. CONCLUSION:   The burden of viral hepatitis-related HCC is substantial.
      Despite treatment advances in recent years, there has been no significant
      improvement in HCC survival. Efforts to improve HCC screening and early diagnosis
      are required to deliver curative treatment which clearly has a survival
      advantage.

PMID- 22607545
TI  - Repair of the double-strand breaks induced by low energy electrons: a modelling
      approach.
AB  - PURPOSE: We propose a biochemical mathematical model for the repair of double
      strand breaks (DSB) induced by low energy electron tracks, and determine the
      repair time for simple and complex DSB. MATERIALS AND METHODS: The track
      structure code KURBUC_liq was used to simulate electron tracks in liquid water.
      All possible sites of energy depositions and reactions of water radicals in the
      nucleobases of an atomistic model of DNA were located, and the types of damage
      were determined. The initial induced DSB were subjected to a mechanistic model of
      Nonhomologous end-joining (NHEJ) repair. RESULTS: Data are presented for the
      initial and residual yield of DSB induced by low energy electrons. The model of
      repair was verified by comparing the kinetics of the unrejoined DSB with the
      experimental data for the V79 - 4 hamster cells irradiated with 15 Gy of Carbon-K
      (C(K)) 278 eV ultrasoft X-rays. The residual unrepaired DSB in the duplex DNA is
      presented in the time interval up to 3 hours. The calculated repair time for the
      simple and complex DSB are presented. CONCLUSION: With the hypothesis that
      complex DSB take longer time to repair than the simple type DSB, the model
      provides an estimate of DSB repair kinetics of experimental data.

PMID- 22607547
TI  - The Pseudomonas syringae HrpJ protein controls the secretion of type III
      translocator proteins and has a virulence role inside plant cells.
AB  - The bacterial plant pathogen Pseudomonas syringae injects effector proteins into
      plant cells via a type III secretion system (T3SS), which is required for
      pathogenesis. The protein HrpJ is secreted by P. syringae and is required for a
      fully functional T3SS. A hrpJ mutant is non-pathogenic and cannot inject
      effectors into plant cells or secrete the harpin HrpZ1. Here we show that the
      hrpJ mutant also cannot secrete the harpins HrpW1 and HopAK1 or the translocator
      HrpK1, suggesting that these proteins are required in the translocation
      (injection) of effectors into plant cells. Complementation of the hrpJ mutant
      with secretion incompetent HrpJ derivatives restores the secretion of HrpZ1 and
      HrpW1 and the ability to elicit a hypersensitive response, a measure of
      translocation. However, growth in planta and disease symptom production is only
      partially restored, suggesting that secreted HrpJ may have a direct role in
      virulence. Transgenic Arabidopsis plants expressing HrpJ-HA complemented the
      virulence phenotype of the hrpJ mutant expressing a secretion incompetent HrpJ
      derivative and were reduced in their immune responses. Collectively, these data
      indicate that HrpJ has a dual role in P. syringae: inside bacterial cells HrpJ
      controls the secretion of translocator proteins and inside plant cells it
      suppresses plant immunity.

PMID- 22607546
TI  - Effects of tailored neck-shoulder pain treatment based on a decision model guided
      by clinical assessments and standardized functional tests. A study protocol of a
      randomized controlled trial.
AB  - BACKGROUND: A major problem with rehabilitation interventions for neck pain is
      that the condition may have multiple causes, thus a single treatment approach is
      seldom efficient. The present study protocol outlines a single blinded randomised
      controlled trial evaluating the effect of tailored treatment for neck-shoulder
      pain. The treatment is based on a decision model guided by standardized clinical
      assessment and functional tests with cut-off values. Our main hypothesis is that
      the tailored treatment has better short, intermediate and long-term effects than
      either non-tailored treatment or treatment-as-usual (TAU) on pain and function.
      We sub-sequentially hypothesize that tailored and non-tailored treatment both
      have better effect than TAU. METHODS/DESIGN: 120 working women with minimum six
      weeks of nonspecific neck-shoulder pain aged 20-65, are allocated by minimisation
      with the factors age, duration of pain, pain intensity and disability in to the
      groups tailored treatment (T), non-tailored treatment (NT) or treatment-as-usual
      (TAU). Treatment is given to the groups T and NT for 11 weeks (27 sessions evenly
      distributed). An extensive presentation of the tests and treatment decision model
      is provided. The main treatment components are manual therapy, cranio-cervical
      flexion exercise and strength training, EMG-biofeedback training, treatment for
      cervicogenic headache, neck motor control training. A decision algorithm based on
      the baseline assessment determines the treatment components given to each
      participant of T- and NT-groups. Primary outcome measures are physical
      functioning (Neck Disability Index) and average pain intensity last week (Numeric
      Rating Scale). Secondary outcomes are general improvement (Patient Global
      Impression of Change scale), symptoms (Profile Fitness Mapping neck
      questionnaire), capacity to work in the last 6 weeks (quality and quantity) and
      pressure pain threshold of m. trapezius. Primary and secondary outcomes will be
      reported for each group with effect size and its precision. DISCUSSION: We have
      chosen not to include women with psychological ill-health and focus on biomedical
      aspects of neck pain. Future studies should aim at including psychosocial aspects
      in a widened treatment decision model. No important adverse events or side
      effects are expected.

PMID- 22607548
TI  - Chewing number is related to incremental increases in body weight from 20 years
      of age in Japanese middle-aged adults.
AB  - BACKGROUND: Eating habits are associated with both current obesity and
      incremental increases in body weight from young adulthood, but no study has
      focused on chewing number during meals among community residents. OBJECTIVE: This
      study focused on the relationship between chewing number and incremental
      increases in body weight from 20 years of age. METHODS: A total of 93 persons
      aged 35-61 years participated. The subjects were asked to set the device and
      record their chewing number during each meal on a particular day. They were also
      asked whether their body weight had increased by 10 kg or more since they were 20
      years old. RESULTS: The body weight of 28 subjects (30%) had increased more than
      10 kg since the age of 20 years. Total chewing number showed a relationship with
      such body weight increases. The odds ratio of weight increments of more than 10
      kg for the lowest tertile group was 4.6 [95% confidence interval (CI), 1.3-16.2]
      relative to the highest tertile group (Model 1). The odds ratio of weight
      increments for the lowest tertile group increased to 6.3 (95% CI, 1.6-25.4) in
      Model 2 and to 9.1 (95% CI, 1.7-49.8) in Model 3. CONCLUSION: Although this study
      was limited because it did not consider all risk factors, categorical chewing
      number was related independently to body weight increments of more than 10 kg
      from 20 years of age.

PMID- 22607549
TI  - NetMets: software for quantifying and visualizing errors in biological network
      segmentation.
AB  - One of the major goals in biomedical image processing is accurate segmentation of
      networks embedded in volumetric data sets. Biological networks are composed of a
      meshwork of thin filaments that span large volumes of tissue. Examples of these
      structures include neurons and microvasculature, which can take the form of both
      hierarchical trees and fully connected networks, depending on the imaging
      modality and resolution. Network function depends on both the geometric structure
      and connectivity. Therefore, there is considerable demand for algorithms that
      segment biological networks embedded in three-dimensional data. While a large
      number of tracking and segmentation algorithms have been published, most of these
      do not generalize well across data sets. One of the major reasons for the lack of
      general-purpose algorithms is the limited availability of metrics that can be
      used to quantitatively compare their effectiveness against a pre-constructed
      ground-truth. In this paper, we propose a robust metric for measuring and
      visualizing the differences between network models. Our algorithm takes into
      account both geometry and connectivity to measure network similarity. These
      metrics are then mapped back onto an explicit model for visualization.

PMID- 22607550
TI  - Double-barrel stent-assisted coiling of a basilar artery fenestration aneurysm.
AB  - BACKGROUND AND PURPOSE: Basilar artery fenestration aneurysms are rare aneurysms,
      posing unique challenges for endovascular treatment. We report a case of
      successful treatment of a wide-necked basilar artery fenestration aneurysm with a
      novel double-barrel stent-assisted coiling technique. CLINICAL PRESENTATION: A 50
      year-old woman presented with headaches. Evaluation revealed an unruptured 7-mm
      broad-based basilar artery fenestration aneurysm that incorporated both limbs of
      the basilar fenestration and both distal vertebral arteries. INTERVENTION: A 4.5
      mm * 22 mm Enterprise stent (Codman Neurovascular, Raynham, MA, USA) was deployed
      from the right limb of the basilar fenestration into the right distal vertebral
      artery. Similarly, a 2.5 mm * 20 mm Neuroform EZ stent (Boston Scientific,
      Natick, MA, USA) was placed from the left limb of the basilar fenestration into
      the left distal vertebral artery. Following stent deployment, the aneurysm was
      treated with coil-embolization through a jailed microcatheter. CONCLUSION: In the
      case presented, a double-barrel stent configuration enabled dense coil
      embolization of the aneurysm as well as preservation of both basilar fenestration
      limbs and both distal vertebral arteries.

PMID- 22607551
TI  - Thermally-induced structural and chemical alteration of organic-walled
      microfossils: an experimental approach to understanding fossil preservation in
      metasediments.
AB  - The identification and confirmation of bona fide Archean-Paleoproterozoic
      microfossils can prove to be a challenging task, further compounded by diagenetic
      and metamorphic histories. While structures of likely biological origin are not
      uncommon in Precambrian rocks, the search for early fossil life has been
      disproportionately focused on lesser thermally altered rocks, typically
      greenschist or lower-grade metamorphism. Recently, however, an increasing number
      of inferred micro- and macrofossils have been reported from higher-grade
      metasediments, prompting us to experimentally test and quantify the
      preservability of organic-walled microfossils over varying durations of
      controlled heating and under two differing redox conditions. Because of their
      relatively low-intensity natural thermal alteration, acritarchs from the
      Mesoproterozoic Ruyang Group were chosen as subjects for experimental heating at
      approximately 500 degrees C, with durations ranging from 1 to 250 days and in
      both oxic (normal present day conditions) and anoxic conditions. Upon extraction,
      the opacity, reflectivity, color, microchemistry, and microstructures of the
      heated acritarchs were characterized using optic microscopy, scanning electron
      microscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy. The results
      differ for acritarchs prepared under oxic vs. anoxic conditions, with the anoxic
      replicates surviving experimental heating longer and retaining biological
      morphologies better, despite an increasing degree of carbonization with
      continuous heating. Conversely, the oxic replicates show aggressive degradation.
      In conjunction with fossils from high-grade metasediments, our data illustrate
      the preservational potential of organic-walled microfossils subjected to
      metamorphism in reducing conditions, offer insights into the search for
      microfossils in metasediments, and help to elucidate the influence of time on the
      carbonization/graphitization processes during thermal alteration.

PMID- 22607553
TI  - A randomized controlled trial of a senior centre group programme for increasing
      social support and preventing depression in elderly people living at home in
      Norway.
AB  - BACKGROUND: Late-life depression is a common condition and a challenging public
      health problem. A lack of social support is strongly associated with
      psychological distress. Senior centres seem to be suitable arenas for community
      based health promotion interventions, although few studies have addressed this
      subject. The objectives were to examine the effect of a preventive senior centre
      group programme consisting of weekly meetings, on social support, depression and
      quality of life. METHODS: A questionnaire was sent to a random sample of 4,000
      persons over 65 in Oslo, and a total of 2,387 completed questionnaires were
      obtained. These subjects served as a basis for recruitment of participants for a
      trial, with scores on HSCL-10 being used as a main inclusion criterion. A total
      of 138 persons were randomized into an intervention group (N = 77) and control
      group (N = 61). Final analyses included 92 persons. Social support (OSS-3),
      depression (BDI), life satisfaction and health were measured in interviews at
      baseline and after 12 months (at the end of the intervention programme).
      Perceptions of benefits from the intervention were also measured. Mean scores,
      SD, SE and CI were used to describe the changes in outcomes. Effect sizes were
      calculated based on the original scales and as Cohen's d. Paired sample tests and
      ANOVA were used to test group differences. RESULTS: There was an increase in
      social support in both groups, but greatest in the intervention group. The level
      of depression increased for both groups, but more so in the control than the
      intervention group. There was a decrease in life satisfaction, although the
      decrease was largest among controls. There were almost no differences in reported
      health between groups. However, effect sizes were small and differences were not
      statistically significant. In contrast, most of the participants said the
      intervention meant much to them and led to increased use of the centre.
      CONCLUSIONS: In all probability, the intervention failed to meet optimistic
      targets, but possibly met quite modest ones. Since intention-to-treat analysis
      was not possible, we do not know the effect on the intervention group as a whole.
      A further evaluation of these programmes is necessary to expand the group
      programme. For the depressed, more specialized programmes to cope with depression
      may be a more appropriate intervention. TRIAL REGISTRATION: DRKS00003120 on DRKS.

PMID- 22607552
TI  - Infection and upregulation of proinflammatory cytokines in human brain vascular
      pericytes by human cytomegalovirus.
AB  - BACKGROUND: Congenital human cytomegalovirus (HCMV) infections can result in CNS
      abnormalities in newborn babies including vision loss, mental retardation, motor
      deficits, seizures, and hearing loss. Brain pericytes play an essential role in
      the development and function of the blood-brain barrier yet their unique role in
      HCMV dissemination and neuropathlogy has not been reported. METHODS: Primary
      human brain vascular pericytes were exposed to a primary clinical isolate of HCMV
      designated 'SBCMV'. Infectivity was analyzed by microscopy, immunofluorescence,
      Western blot, and qRT-PCR. Microarrays were performed to identify proinflammatory
      cytokines upregulated after SBCMV exposure, and the results validated by real
      time quantitative polymerase chain reaction (qPCR) methodology. In situ cytokine
      expression of pericytes after exposure to HCMV was examined by ELISA and in vivo
      evidence of HCMV infection of brain pericytes was shown by dual-labeled
      immunohistochemistry. RESULTS: HCMV-infected human brain vascular pericytes as
      evidenced by several markers. Using a clinical isolate of HCMV (SBCMV),
      microscopy of infected pericytes showed virion production and typical cytomegalic
      cytopathology. This finding was confirmed by the expression of major immediate
      early and late virion proteins and by the presence of HCMV mRNA. Brain pericytes
      were fully permissive for CMV lytic replication after 72 to 96 hours in culture
      compared to human astrocytes or human brain microvascular endothelial cells
      (BMVEC). However, temporal transcriptional expression of pp65 virion protein
      after SBCMV infection was lower than that seen with the HCMV Towne laboratory
      strain. Using RT-PCR and dual-labeled immunofluorescence, proinflammatory
      cytokines CXCL8/IL-8, CXCL11/ITAC, and CCL5/Rantes were upregulated in SBCMV
      infected cells, as were tumor necrosis factor-alpha (TNF-alpha), interleukin-1
      beta (IL-1beta), and interleukin-6 (IL-6). Pericytes exposed to SBCMV elicited
      higher levels of IL-6 compared to both mock-infected as well as heat-killed virus
      controls. A 6.6-fold induction of IL-6 and no induction TNF-alpha was observed in
      SBCMV-infected cell supernatants at 24 hours postinfection. Using archival brain
      tissue from a patient coinfected with HCMV and HIV, we also found evidence of
      HCMV infection of pericytes using dual-label immunohistochemistry, as monitored
      by NG2 proteoglycan staining. CONCLUSION: HCMV lytic infection of primary human
      brain pericytes suggests that pericytes contribute to both virus dissemination in
      the CNS as well as neuroinflammation.

PMID- 22607555
TI  - T cell-specific siRNA delivery using antibody-conjugated chitosan nanoparticles.
AB  - The intracellular delivery of small interfering RNA (siRNA) plays a key role in
      RNA interference (RNAi) and provides an emerging technique to treat various
      diseases, including infectious diseases. Chitosan has frequently been used in
      gene delivery applications, including siRNA delivery. However, studies regarding
      the modification of chitosan with antibodies specifically targeting T cells are
      lacking. We hypothesized that chitosan nanoparticles modified with T cell
      specific antibodies would be useful for delivering siRNA to T cells. CD7-specific
      single-chain antibody (scFvCD7) was chemically conjugated to chitosan by
      carbodiimide chemistry, and nanoparticles were prepared by a complex coacervation
      method in the presence of siRNA. The mean diameter and zeta potential of the
      scFvCD7-chitosan/siRNA nanoparticles were approximately 320 nm and +17 mV,
      respectively, and were not significantly influenced by the coupling of antibody
      to chitosan. The cellular association of antibody-conjugated nanoparticles to
      CD4+ T cell lines as well as gene silencing efficiency in the cells was
      significantly improved compared to nonmodified chitosan nanoparticles. This
      approach to introducing T cell-specific antibody to chitosan nanoparticles may
      find useful applications for the treatment of various infectious diseases. 

PMID- 22607554
TI  - Chronic modulation of AMP-Kinase, Akt and mTOR pathways by ionizing radiation in
      human lung cancer xenografts.
AB  - INTRODUCTION: Earlier, we showed that in cancer cells, AMP-activated kinase
      (AMPK) participates in a signal transduction pathway involving ATM-AMPK
      p53/p21cip1 which is activated by ionizing radiation (IR) to mediate G2-M arrest
      and enhanced cytotoxicity. We also observed that AMPK modulates ATM expression
      and activity and the IR response of the Akt-mTOR pathway. Since the ATM, AMPK and
      Akt pathways are key targets of novel radio-sensitizing therapeutics, we examined
      the chronic modultion of expression and activity of those pathways by IR alone in
      xenograft models of lung cancer. METHODS: Immuno-compromised mice were grafted
      with human lung A549 and H1299 cells, were treated with a single fraction of 0 or
      10 Gy, and left to grow for 8 weeks. Extracted tumors were subjected to lysis and
      immunoblotting or fixation and immunohistochemical analysis. RESULTS: IR
      inhibited significantly xenograft growth and was associated with increased
      expression of Ataxia Telengiectasia Mutated (ATM) and enhanced phosphorylation of
      two ATM targets, H2Ax and checkpoint kinase Chk2. Irradiated tumours showed
      increased total AMPK levels and phosphorylation of AMPK and its substrate Acetyl
      CoA Carboxylase (ACC). IR led to enhanced expression and phosphorylation of p53
      and cyclin dependent kinase inhibitors p21cip1 and p27kip1. However, irradiated
      tumours had reduced phosphorylation of Akt, mTOR and it's target translation
      initiation inhibitor 4EBP1. Irradiated xenografts showed reduced microvessel
      density, reduced expression of CD31 but increased expression of hypoxia-induced
      factor 1A (HIF1a) compared to controls. CONCLUSION: IR inhibits epithelial cancer
      tumour growth and results in sustained expression and activation of ATM-Chk2, and
      AMPK-p53/p21cip1/p27kip1 but partial inhibition of the Akt-mTOR signaling
      pathways. Future studies should examine causality between those events and
      explore whether further modulation of the AMPK and Akt-mTOR pathways by novel
      therapeutics can sensitize lung tumours to radiation.

PMID- 22607557
TI  - Anaphylaxis admissions to UK critical care units between 2005 and 2009.
AB  - Anaphylaxis is a life-threatening emergency that may necessitate admission to a
      critical care unit. There are no reports of the frequency of admission to
      critical care units for patients with anaphylaxis or indeed any description of
      their demographic characteristics or outcomes. We analysed all physician
      diagnosed cases of anaphylaxis over a 5-year period in national audit data from
      critical care units across the UK. Over the period 2005-2009, there were 81
      paediatric and 1269 adult admissions with anaphylaxis admitted to UK critical
      care units (0.1% of admissions to paediatric units and 0.3% of admissions to
      adult units). Absolute numbers in both children and adults rose year on year.
      There were comparable proportions of admissions in female and male children
      (female = 47% and male = 53%; rate ratios (RR) = 0.88, 95% CI 0.64-1.20), but a
      greater proportion of adult female admissions (female = 65% and male = 35%; RR =
      1.83, 95% CI 1.68-1.99). Survival to unit discharge was 95% (77/81) for children,
      and survival to hospital discharge was 92% (1166/1269) for adults. Each UK
      critical care unit is likely to see at least one anaphylaxis case per year. The
      number of admissions has risen in both children and adults. Although admission
      ratios between the sexes were comparable in children, there was a female
      preponderance in adult life. Survival rates were high at over 90%.

PMID- 22607556
TI  - Combinations of griffithsin with other carbohydrate-binding agents demonstrate
      superior activity against HIV Type 1, HIV Type 2, and selected carbohydrate
      binding agent-resistant HIV Type 1 strains.
AB  - Carbohydrate-binding agents (CBAs) are potential HIV microbicidal agents with a
      high genetic barrier to resistance. We wanted to evaluate whether two mannose
      specific CBAs, recognizing multiple and often distinct glycan structures on the
      HIV envelope gp120, can interact synergistically against HIV-1, HIV-2, and HIV-1
      strains that were selected for resistance against particular CBAs [i.e., 2G12 mAb
      and microvirin (MVN)]. Paired CBA/CBA combinations mainly showed synergistic
      activity against both wild-type HIV-1 and HIV-2 but also 2G12 mAb- and MVN
      resistant HIV-1 strains as based on the median effect principle with combination
      indices (CIs) ranging between 0.29 and 0.97. Upon combination, an increase in
      antiviral potency of griffithsin (GRFT) up to ~12-fold (against HIV-1), ~8-fold
      (against HIV-2), and ~6-fold (against CBA-resistant HIV-1) was observed. In
      contrast, HHA/GNA combinations showed additive activity against wild-type HIV-1
      and HIV-2 strains, but remarkable synergy with HHA and GNA was observed against
      2G12 mAb- and MVN-resistant HIV-1 strains (CI, 0.64 and 0.49, respectively).
      Overall, combinations of GRFT and other CBAs showed synergistic activity against
      HIV-1, HIV-2, and even against certain CBA-resistant HIV-1 strains. The CBAs
      tested appear to have distinct binding patterns on the gp120 envelope and
      therefore do not necessarily compete with each other's glycan binding sites on
      gp120. As a result, there might be no steric hindrance between two different CBAs
      in their competition for glycan binding (except for the HHA/GNA combination).
      These data are encouraging for the use of paired CBA combinations in topical
      microbicide applications (e.g., creams, gels, or intravaginal rings) to prevent
      HIV transmission.

PMID- 22607558
TI  - Assessment of ischaemia-modified albumin level in patients with psoriasis.
AB  - BACKGROUND: Ischaemia-modified albumin (IMA) is increased in diseases associated
      with oxidative stress, as detected using the albumin cobalt-binding test.
      Oxidative stress plays an important role in the development of psoriasis. AIM: To
      investigate circulating IMA levels in patients with psoriasis and its association
      with the disease characteristics. METHODS: Serum IMA and albumin concentrations
      were evaluated in 26 patients with psoriasis and 26 healthy controls matched for
      age, gender and body mass index. Levels of albumin, IMA and adjusted IMA were
      compared between the groups. RESULTS: IMA and adjusted IMA were significantly
      higher in patients with psoriasis [0.55 +/- 0.04 and 0.54 +/- 0.05 absorbance
      units (ABSU), respectively] than in healthy controls (0.38 +/- 0.04 and 0.38 +/-
      0.05 ABSU, respectively). The two groups had similar albumin levels, but there
      was a negative correlation between IMA and albumin levels in patients with
      psoriasis. IMA did not correlate with any disease characteristics. CONCLUSIONS:
      IMA levels are higher in patients with psoriasis than in healthy controls. IMA
      might be produced through an adaptive response to chronic hypoxia and oxidative
      stress, which might play a role in the systemic inflammation seen in psoriasis.

PMID- 22607559
TI  - Self-assembled vesicles prepared from amphiphilic cyclodextrins as drug carriers.
AB  - Controlled self-assembly of amphiphilic cyclodextrin is always a challenging
      topic in the field of supramolecular chemistry, since it provides the spontaneous
      generation of well-defined aggregation with functional host sites with great
      potential applications in drug-carrier systems. beta-Cyclodextrin modified with
      an anthraquinone moiety (1) was successfully synthesized. In the aqueous
      solution, 1 was found able to self-assemble into vesicles, which was
      characterized in detail by TEM, SEM, EFM, and DLS. The formation mechanism of the
      vesicles was suggested based on the 2D ROESY and UV-vis results, and further
      verified by the MD simulation. Subsequently, the stimuli response property of the
      vesicles, including to Cu(2+) and H(+), was also studied. The vesicles can
      efficiently load Paclitaxel inside the membrane with functional macrocyclic
      cavities available, which can further carry small molecules, such as ferrocene.
      The vesicles loading with Paclitaxel have remarkable anticancer effects. This
      work will provide new strategy in drug-carrier systems and tumor treatment
      methods.

PMID- 22607560
TI  - Comparative proteomic analysis of virulent and rifampicin-attenuated
      Flavobacterium psychrophilum.
AB  - Flavobacterium psychrophilum is the aetiologic agent of bacterial coldwater
      disease and rainbow trout fry syndrome. In this study, we compared a wild-type
      strain (CSF 259-93) with a rifampicin-resistant strain and virulence-attenuated
      strain of F. psychrophilum (CSF 259-93B.17). The attenuated strain harboured a
      mutation in the rpoB gene consistent with resistance to rifampicin. Two
      dimensional polyacrylamide gel electrophoresis (2D-PAGE) and mass spectrometry
      demonstrated an altered proteome with eight proteins characteristic for the
      parent strain and six that were unique to the attenuated strain. Immunoblotting
      with a diagnostic monoclonal antibody (FL-43) identified a putative antigen
      (FP1493) that was subsequently cloned, expressed as a recombinant protein and
      confirmed as recognized by FL-43. 2D-PAGE, immunoblotting with rainbow trout,
      Oncorhynchus mykiss (Walbaum), convalescent antisera and mass spectrometry of
      bacterial whole-cell lysates revealed several uniquely expressed immunoreactive
      proteins including FP1493. An FP1493 recombinant subunit vaccine was tested, but
      did not provide protection against challenge with the CSF259-93 strain. While the
      exact mechanism responsible for altered protein synthesis and attenuation of CSF
      259-93B.17 is still unknown, the differentially expressed immunoreactive proteins
      are a valuable resource to develop subunit vaccines and to identify proteins that
      are potentially involved in disease.

PMID- 22607561
TI  - My experiences with apheresis.

PMID- 22607562
TI  - Plasma separation by centrifugation and subsequent plasma filtration: impact on
      survival in a pig model of sepsis.
AB  - The impact on survival of a combination of plasma separation by centrifugation
      and subsequent plasma filtration was tested in a bacterial sepsis model in pigs.
      In this animal study 19 pigs were included. Groups II and III received an
      intravenous lethal dose of live Staphylococcus aureus over 1 h; group I received
      saline (non-septic control--NC). Groups I and II were treated by an
      extracorporeal circuit consisting of online centrifugation and subsequent plasma
      filtration (group II: treated group--TG) for 4 h; group III had no specific
      treatment (septic control, SC). The observation time was 7 days. All animals of
      group I (NC) and group II (TG) survived, while all animals of group III (SC) died
      during the observation time. Extracorporeal therapy with online centrifugation
      and plasma filtration significantly improved survival in a pig model of sepsis.
      Further studies with this approach are encouraged.

PMID- 22607563
TI  - Intermittent granulocyte and monocyte apheresis versus mercaptopurine for
      maintaining remission of ulcerative colitis: a pilot study.
AB  - The effect of granulocyte and monocyte adsorption apheresis (GMA) on prevention
      of relapse of ulcerative colitis (UC) is not clear. This was a pilot open
      labeled, prospective, randomized, unblinded study to compare the tolerability and
      efficacy of intermittent GMA (once every 2 weeks) with mercaptopurine to maintain
      remission of UC. Twenty-one patients with UC, who had achieved remission by
      induction therapies were randomly assigned to receive either intermittent GMA (N
      = 10) or oral mercaptopurine (0.5 mg/kg per day; N = 11). The study period was 24
      months. The rate of the patients maintaining remission and the incidences of
      adverse effects were compared between the two groups. At 24 months, seven of 10
      patients (70.0%) on intermittent GMA and seven of 11 patients (63.6%, P = 1.00)
      on oral mercaptopurine were still in remission. Three patients relapsed in each
      group. One patient taking mercaptopurine, but none receiving intermittent GMA,
      dropped out because of adverse effects. Intermittent therapy with GMA was well
      tolerated and a substantial proportion of patients maintained remission.
      Intermittent GMA therapy in maintaining remission of UC merits further
      investigation.

PMID- 22607564
TI  - Excessive fall of blood pressure during maintenance hemodialysis in patients with
      chronic renal failure is induced by vascular malfunction and imbalance of
      autonomic nervous activity.
AB  - Acute hypotension during maintenance hemodialysis (HD) is not only a critical
      complication, but also an independent risk factor for mortality in patients with
      chronic renal failure (CRF). This study was designed to clarify the mechanisms
      underlying excessive fall of blood pressure during HD. Fifty-six CRF patients
      with HD thrice a week were divided into two groups according to the intradialytic
      hypotension episodes after 4 weeks of the observation period; the hypotension
      group, showing four or more episodes of intradialytic hypotension, and the non
      hypotension group, showing three episodes of intradialytic hypotension or less.
      The intradialytic hypotension was defined as a fall of >=30 mm Hg in the systolic
      blood pressure during HD. The brachial-ankle pulse wave velocity (ba-PWV), serum
      high-sensitivity (hs)-CRP, reactive oxygen species (ROS) generation, and serum
      malondialdehyde-modified LDL (MDA-LDL) were measured before HD. The high-
      frequency (HF) and low-frequency components (LF) of the heart rate variability
      and entropy were analyzed by the maximal entropy method. The ba-PWV, hs-CRP, ROS
      generation, and MDA-LDL were significantly higher in the hypotension group than
      in the non-hypotension group. HF, LF/HF, and entropy during HD increased
      significantly in the non-hypotension group, while entropy during HD decreased
      significantly in the hypotension group as compared with the baseline. LF/HF and
      entropy during HD were significantly lower in the hypotension group than in the
      non-hypotension group. These findings suggest that the major factors causing
      excessive fall of blood pressure during HD in patients with CRF might be vascular
      malfunction and imbalance of autonomic nervous activity.

PMID- 22607565
TI  - High mortality rate of infectious diseases in dialysis patients: a comparison
      with the general population in Japan.
AB  - Infectious disease is the second leading cause of death among dialysis patients,
      and it is generally assumed that the mortality rate of infectious disease is
      considerably higher in dialysis patients than in the general population. There
      are no comprehensive studies on this issue and on the contribution of each
      category of infectious disease to excess mortality in dialysis patients in Japan.
      We used mortality data reported to the Japanese Society for Dialysis Therapy and
      national Vital Statistics data for 2008 and 2009. We calculated standardized
      mortality ratios and compared the mortality rates for each category of infectious
      disease. During the 2-year study period, 274,683 and 10,435 deaths from
      infectious diseases were recorded in 126 million people and 273,237 dialysis
      patients, respectively. The standardized mortality ratio for all infectious
      diseases was 7.5 (95% confidence interval, 7.3-7.6) in dialysis patients with
      respect to the general population in Japan. The categories of infectious disease
      with a significantly higher standardized mortality ratio among the dialysis
      patients were sepsis, peritonitis, influenza, tuberculosis, and pneumonia and in
      that order. In particular, the mortality rate of sepsis contributed to 69.5% of
      the difference in infectious disease mortality between dialysis patients and the
      general population. This study underlines markedly increased mortality from
      infectious diseases, particularly from sepsis, in dialysis patients compared with
      the general population.

PMID- 22607566
TI  - Brachial-ankle pulse wave velocity and the cardio-ankle vascular index as a
      predictor of cardiovascular outcomes in patients on regular hemodialysis.
AB  - Brachial-ankle pulse wave velocity (baPWV) and the cardio-ankle vascular index
      (CAVI) are both used to evaluate arterial stiffness. The aim of the present study
      is to determine whether baPWV or CAVI is superior as a marker of arterial
      stiffness in hemodialysis (HD) patients. Of 194 patients, 59 patients had been
      excluded from the study due to advanced age over 76 years old (n = 29), or
      abnormal ankle-brachial pressure index (ABI) (<0.90 or >=1.30) (n = 30). We then
      followed the 135 patients (age: 60 +/- 11 years, time on HD: 110 +/- 93 months)
      for the 63 +/- 4 (55-70) months. Thirty-two (23.7%) patients had expired, 22 of
      them of cardiovascular (CV) causes. There were 37 fatal and non-fatal CV events.
      Kaplan-Meier analysis revealed that the patients with the highest tertile of
      baPWV (>=16.6 m/s) had a significantly lower survival rate (P < 0.01) when
      compared with the second (13.4 <= baPWV < 16.6 m/s) and the lowest tertiles
      (<13.4 m/s). Cox hazards analysis after adjustment for comorbid risk factors
      revealed that the top tertile of baPWV was a determinant of CV death (hazards
      ratio [HR]: 16.9 [1.1-251.8], P < 0.05) In contrast, CAVI did not associate with
      CV mortality or events. These findings suggest that baPWV is superior to CAVI as
      a predictor of CV outcomes in patients on regular HD.

PMID- 22607567
TI  - Upper limb disability in hemodialysis patients: evaluation of contributing
      factors aside from amyloidosis.
AB  - This cross-sectional case-control study evaluated upper limb muscle strength and
      shoulder mobility in hemodialysis (HD) patients with arteriovenous fistula or
      graft. Twenty-five adult patients on thrice-a-week HD treatment for 6 months at
      least, were selected for the study. In all the patients and control subjects,
      handgrip tests and tests of range of motion in the upper extremities were
      evaluated by physiotherapy tests. Patients on HD showed lower muscle strength
      than age and sex matched subjects without severe chronic kidney disease (right:
      30.1 +/- 11.6 vs 40.5 +/- 15.1 kg, P < 0.001; left 29.1 +/- 12.9 vs 40.7 +/- 11.1
      kg, P < 0.01), and a reduced range of shoulder mobility. The presence of fistula
      or graft was associated with a greater limitation of both active (74.0 +/- 18.3
      vs 85.2 +/- 8.8  degrees , P < 0.01) and passive (82.2 +/- 9.9 vs 87.2 +/- 6.6 
      degrees , P < 0.05) extra-rotation than the contralateral limb, with a higher
      prevalence of impingement (72 vs 36%, P < 0.05). Muscle strength was related to
      albumin and inversely to age; whereas beta(2) -microglobulin and CRP serum levels
      were associated with impairment of passive and active extra-rotation of the
      shoulder that was free from the fistula or graft. In summary, patients on HD have
      a reduced range of shoulder mobility and marked reduction of muscle strength. The
      abnormalities are more prevalent in upper limbs with fistula or grafts. The
      arteriovenous fistula or graft may worsen the disability of the patient's upper
      limbs presumably due to the obligate position required during the HD sessions.
      Proper pre- and post-dialysis exercise programs should be implemented to maintain
      mobility and strength of the upper limbs.

PMID- 22607568
TI  - Effect of alfacalcidol therapy on the survival of chronic hemodialysis patients.
AB  - The aim of this study was to determine the relationship between alfacalcidol
      therapy and the outcomes of chronic hemodialysis (HD) patients. We collected
      demographic and clinical baseline data from 190 prevalent HD patients in a
      regional Japanese cohort. A 5-year survival analysis was performed according to
      whether the patients were receiving calcitriol analog therapy. Alfacalcidol
      therapy at a mean dose of 5.2 +/- 1.8 ug/week was performed in 89 (46.8%) of the
      190 patients. We recorded 38 deaths during the follow-up period, including 19
      deaths from cardiovascular events. A Kaplan-Meier analysis demonstrated that the
      alfacalcidol users had a significantly lower rate of all-cause mortality and
      cardiovascular mortality than the non-users. According to a multivariate Cox
      proportional hazards model, in addition to the use of alfacalcidol (HR=0.347
      [0.155-0.714]; P = 0.0035), serum CRP levels (HR= 1.746 [1.184-2.442]; P =
      0.0071) and non-HDL-cholesterol levels (HR=1.012 [1.001-1.022]; P = 0.0267) were
      identified as independent predictors of all-cause mortality, and the presence of
      diabetes mellitus (HR=3.720 [1.182-12.398]; P = 0.0246) was identified as an
      independent predictor of cardiovascular mortality. These findings suggest that
      low-dose alfacalcidol therapy provides a survival advantage to chronic HD
      patients.

PMID- 22607569
TI  - Perioperative outcomes of laparoscopic radical nephrectomy for renal cell
      carcinoma in patients with dialysis-dependent end-stage renal disease.
AB  - The aims of this study were: (i) to analyze the perioperative outcomes of
      laparoscopic radical nephrectomy for renal cell carcinoma in patients with
      dialysis-dependent end-stage renal disease and (ii) to reveal perioperative
      management problems that are unique to these patients. Between June 2004 and June
      2011, laparoscopic radical nephrectomy was performed in 39 patients who had renal
      cell carcinoma and dialysis-dependent end-stage renal disease. The operative
      outcomes of these patients were compared with the operative outcomes of 104 non
      end-stage renal disease patients with sporadic renal cell carcinoma who underwent
      laparoscopic radical nephrectomy during the same period. Laparoscopic surgery was
      completed in thirty-eight end-stage renal disease patients. One patient was
      converted to open surgery because of an intraoperative injury to the inferior
      vena cava. This patient was excluded from the analysis. The mean operative time
      was 240 min; blood loss, 157 mL; and postoperative hospital stay, 9.6 days.
      Postoperative complications were observed in six patients, as follows:
      retroperitoneal hematoma and abscess in one patient, thrombosis of the
      arteriovenous fistula in three patients, pneumonia in one patient, and
      gastrointestinal bleeding in one patient. Eleven patients required blood
      transfusions. There was no significant difference between the end-stage renal
      disease patients and the non-end-stage renal disease patients in the mean
      operative time or the amount of blood loss. In conclusion, laparoscopic radical
      nephrectomy is feasible for dialysis-dependent end-stage renal disease patients,
      as well as for non-end-stage renal disease patients; however, end-stage renal
      disease patients may have a higher probability of experiencing non-life
      threatening complications.

PMID- 22607570
TI  - Morning hypertension determined by self-measurement at home predicts left
      ventricular hypertrophy in patients undergoing continuous ambulatory peritoneal
      dialysis.
AB  - This study aimed to clarify the relationship between blood pressure (BP, mm Hg)
      measured by patients in the morning at home and left ventricular hypertrophy
      (LVH), which is a strong predictor for morbidity and mortality due to
      cardiovascular disease in patients undergoing continuous ambulatory peritoneal
      dialysis (CAPD). We recorded self-measured morning BPs and BPs measured at
      hospital check-ups (hospital BPs) in 33 patients undergoing CAPD (mean age, 64.0
      years) and compared them with left ventricular mass (LVM) derived from
      echocardiographic examinations. The mean morning BP was 137/75, the mean hospital
      BP was 140/80, and the mean LVM (g/m(2.7) : corrected by height) was 61.8. Of the
      subjects, 72.7% had LVH (LVM > 51). The morning BP (systolic) was positively
      correlated with LVM (P = 0.0022, R = 0.508), and the hospital BP (systolic) was
      weakly correlated (P = 0.0534, R = 0.339). The adjusted odds ratio for LVH was
      significantly higher in patients with a morning BP (systolic) >= 135 (15.9; 95%
      CI, 1.3 to 198.5) than in patients with a morning BP (systolic) < 135. In
      conclusion, morning hypertension determined with self-measured BP was positively
      correlated with LVH, therefore self BP monitoring could be a useful method to
      predict LVH in CAPD patients.

PMID- 22607571
TI  - Correlation of coronary artery calcification with pre-hemodialysis bicarbonate
      levels in patients on hemodialysis.
AB  - Coronary artery calcification (CAC) leads to a significant increase in
      cardiovascular morbidity and mortality in hemodialysis (HD) patients. Metabolic
      acidosis, which is common in HD patients, promotes bone resorption in human and
      animals as a result of buffer function of bone, and calcium and phosphate elute
      from bone into blood stream. However, the effect of acidosis on CAC in HD
      patients has never been precisely investigated. This is a cross-sectional
      observational study performed in a single center. One hundred and seven prevalent
      HD patients (35 women and 72 men) underwent electron-beam computed tomography
      (EBCT) to evaluate CAC score (CACS), and then we evaluated associated factors of
      CACS with clinical and laboratory parameters including pre-HD pH and bicarbonate
      levels. Pre-HD pH and bicarbonate levels were 7.35 +/- 0.04, and 17.6 +/- 1.8
      mmol/L, respectively. The pre-HD pH had no significant correlation to CACS (r = 
      0.025, P = 0.81). CACS was significantly negatively correlated with pre-HD
      bicarbonate levels (r = -0.329, P = 0.0009) and serum albumin levels (r = -0.298,
      P = 0.0467), while it was positively correlated with age (r = 0.319, P = 0.0008)
      and HD duration (r = 0.385, P = 0.0004). Serum levels of calcium, phosphorus,
      intact parathyroid hormone, and use of phosphorus binders were not related to
      CACS. Multivariate analysis indicated that plasma pre-HD bicarbonate level was
      independently associated with CACS. The present study showed that blood levels of
      pre-HD bicarbonate were significantly associated with CAC in HD patients. Further
      studies are needed to confirm these results and to determine whether correction
      of metabolic acidosis prevents the development of CAC, one of the features of
      accelerated atherosclerosis in HD patients.

PMID- 22607572
TI  - Myoglobin-induced apoptosis: two pathways related to endoplasmic reticulum
      stress.
AB  - Myoglobin plays an important role in rhabdomyolysis-induced acute kidney injury
      (AKI), but the underlying mechanisms are still unclear. The present study
      investigates myoglobin-induced apoptosis in HK-2 cells (human renal proximal
      tubule cells) to discover some of the mechanisms involved in rhabdomyolysis
      related AKI. Metmyoglobin is reduced to ferrous myoglobin by ascorbic acid, and
      then the HK-2 cells are incubated with ferrous myoglobin. Cell viability is
      measured by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT)
      assay, and cell injury is tested by supernatant lactose dehydrogenase (LDH). Cell
      apoptosis is evaluated by fluorescent microscopy of Hoechst staining and by flow
      cytometry of Annexin V/PI double staining. The apoptosis related protein
      expression is determined by Western blot. HK-2 cells were incubated with 200 uM
      ferrous myoglobin for 24 h, the cell viability decreased and supernatant LDH
      release increased. Hoechst staining indicated more apoptosis after incubation.
      Molecular chaperone glucose-related protein 78 (GRP78), cytochrome C, caspase-9
      started to increase within 3 h after incubation while caspase-4, caspase-8 showed
      no significant change. (iii) When the inositol triphosphate receptor (IP3R)
      calcium channel was blocked by 2-aminoethoxydiphenyl-borinate (2-APB), caspase-9
      was completely inhibited, GRP78 and caspase-4 increased dramatically, and caspase
      3 expression was not affected. The apoptosis in HK-2 cells showed no significant
      change. Apoptosis in HK-2 cells incubated with ferrous myoglobin is an
      endoplasmic reticulum stress induced, IP3R calcium channel mediated, caspase-9
      dependent intrinsic pathway. When the intrinsic pathway was inhibited using an
      IP3R calcium channel blocker, endoplasmic reticulum stress increased, resulting
      in the activation of caspase-4 that cleaved caspase-3 and generated a
      substitutive pathway of apoptosis.

PMID- 22607573
TI  - Efficacy of plasma exchange therapy for Kawasaki disease by cytokine profiling.

PMID- 22607576
TI  - Unusual manifestations of acute Q fever: autoimmune hemolytic anemia and
      tubulointerstitial nephritis.
AB  - Q fever is a worldwide zoonotic infection that caused by Coxiella burnetii, a
      strict intracellular bacterium. It may be manifested by some of the autoimmune
      events and is classified into acute and chronic forms. The most frequent clinical
      manifestation of acute form is a self-limited febrile illness which is associated
      with severe headache, muscle ache, arthralgia and cough. Meningoencephalitis,
      thyroiditis, pericarditis, myocarditis, mesenteric lymphadenopathy, hemolytic
      anemia, and nephritis are rare manifestations. Here we present a case of acute Q
      fever together with Coombs' positive autoimmune hemolytic anemia (AIHA) and
      tubulointerstitial nephritis treated with chlarithromycin, steroids and
      hemodialysis. Clinicians should be aware of such rare manifestations of the
      disease.

PMID- 22607577
TI  - Daidzein improves insulin resistance in ovariectomized rats.
AB  - OBJECTIVE: To determine whether daidzein improves insulin resistance by modifying
      weight gain, visceral fat accumulation, blood lipids and serum cytokines levels
      in ovariectomized Sprague-Dawley rats. MATERIALS AND METHODS: Twenty-eight 12
      week-old female rats were divided into three groups: the sham-operated group
      (SHAM) (n =10), the ovariectomized group receiving daidzein therapy (DAID) (n
      =10), and the ovariectomized control group (Control) (n =8). The rats in the DAID
      group received 50 mg/kg daidzein via gavage daily. Weight and food intake were
      recorded every 2 weeks. All of the animals were euthanized 12 weeks after
      ovariectomy, after which their fasting insulin, glucose, blood lipids, estradiol,
      interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), adiponectin and
      leptin levels were measured. RESULTS: After 12 weeks, the ovariectomized rats
      demonstrated an increase in their body weight and visceral fat; compared to the
      SHAM rats, the ovariectomized rats also experienced a significant increase in
      their serum IL-6 levels and insulin resistance, which was calculated using the
      homeostatic model assessment of insulin resistance (HOMA-IR) (p <0.05). Daidzein
      therapy decreased weight gain, visceral fat, the HOMA-IR index and IL-6 levels
      that were induced by ovariectomy. Rats which had received daidzein therapy had
      lower levels of TNF-alpha, leptin and blood lipids (except for high density
      lipoprotein cholesterol) than the other two groups. IL-6 levels positively
      correlated with the HOMA-IR index in all of the rats after adjustment for body
      weight (r =0.495; p =0.016). CONCLUSION: We conclude that daidzein can improve
      insulin resistance induced by ovariectomy by decreasing weight gain, visceral fat
      accumulation, blood lipids, TNF-alpha, leptin and IL-6 levels.

PMID- 22607578
TI  - Up-regulating the human intestinal microbiome using whole plant foods,
      polyphenols, and/or fiber.
AB  - Whole plant foods, including fruit, vegetables, and whole grain cereals, protect
      against chronic human diseases such as heart disease and cancer, with fiber and
      polyphenols thought to contribute significantly. These bioactive food components
      interact with the gut microbiota, with gut bacteria modifying polyphenol
      bioavailability and activity, and with fiber, constituting the main energy source
      for colonic fermentation. This paper discusses the consequences of increasing the
      consumption of whole plant foods on the gut microbiota and subsequent
      implications for human health. In humans, whole grain cereals can modify fecal
      bacterial profiles, increasing relative numbers of bifidobacteria and
      lactobacilli. Polyphenol-rich chocolate and certain fruits have also been shown
      to increase fecal bifidobacteria. The recent FLAVURS study provides novel
      information on the impact of high fruit and vegetable diets on the gut
      microbiota. Increasing whole plant food consumption appears to up-regulate
      beneficial commensal bacteria and may contribute toward the health effects of
      these foods.

PMID- 22607579
TI  - Single oral doses of netazepide (YF476), a gastrin receptor antagonist, cause
      dose-dependent, sustained increases in gastric pH compared with placebo and
      ranitidine in healthy subjects.
AB  - BACKGROUND: Nonclinical studies have shown netazepide (YF476) to be a potent,
      selective, competitive and orally active gastrin receptor antagonist. AIM: To
      administer to humans for the first time single oral doses of netazepide, to
      assess their tolerability, safety, pharmacokinetics and effect on 24-h gastric
      pH. METHODS: We did two randomised double-blind single-dose studies in healthy
      subjects. The first (n = 12) was a six-way incomplete crossover pilot study of
      rising doses of netazepide (range 0.5-100 mg) and placebo. The second (n = 20)
      was a five-way complete crossover study of netazepide 5, 25 and 100 mg,
      ranitidine 150 mg and placebo. In both trials we collected frequent blood
      samples, measured plasma netazepide and calculated pharmacokinetic parameters. In
      the comparative trial we measured gastric pH continuously for 24 h and compared
      treatments by percentage time gastric pH >=4. RESULTS: Netazepide was well
      tolerated. Median t (max) and t (1/2) for the 100 mg dose were about 1 and 7 h,
      respectively, and the pharmacokinetics were dose-proportional. Netazepide and
      ranitidine each increased gastric pH. Onset of activity was similarly rapid for
      both. All netazepide doses were more effective than placebo (P <= 0.023).
      Compared with ranitidine, netazepide 5 mg was as effective, and netazepide 25 and
      100 mg were much more effective (P <= 0.010), over the 24 h after dosing.
      Activity of ranitidine lasted about 12 h, whereas that of netazepide exceeded 24
      h. CONCLUSIONS: In human: netazepide is an orally active gastrin antagonist, and
      gastrin has a major role in controlling gastric acidity. Repeated-dose studies
      are justified. NCT01538784 and NCT01538797.

PMID- 22607580
TI  - Antioxidant and gastric cytoprotective prostaglandins properties of Cassia
      sieberiana roots bark extract as an anti-ulcerogenic agent.
AB  - BACKGROUND: Cassia sieberiana is a savannah tree with a wide phytotherapeutic
      application including the use of its roots in the management of various stomach
      disorders including gastric ulcer, stomach pains and indigestion. The aim of the
      study is to evaluate the antioxidant, gastric cytoprotective prostaglandins,
      secretory phospholipase A2, phytochemical and acute toxicity properties of Cassia
      sieberiana roots bark extract in a bid to justify its phytotherapeutic
      applications in gastric ulcer. METHODS: Antioxidant and radical scavenging
      activities of the roots bark extract of Cassia sieberiana were assayed. Serum
      secretory phospholipase A2 (sPLA2) concentration and activity and the formation
      of gastric mucosal prostaglandins E2 (PGE2) and I2 (PGI2) were also assessed.
      Comparisons between means were performed using analysis of variance (ANOVA)
      followed by Students Standard Newman-Keuls post hoc analysis to determine
      statistical significance. P < 0.05 was considered significant. RESULTS: The
      extract was found to possess significant ferric reducing antioxidant power and
      can scavenge hydroxyl radicals. The extract also possesses DPPH scavenging
      activity, can chelate ferrous ion and a dose-dependent protective effect against
      lipid peroxidation and free radical generation. Prostaglandin studies showed that
      the roots bark extract dose dependently increased gastric mucosal PGE2 and PGI2
      levels and also decreased serum sPLA2 activity. Phytochemical analyses suggest
      that the roots extract contains polyhydroxyl/phenolic substances. Acute toxicity
      test showed no sign of toxicity up to a dose level of 2000 mg/kg body weight p.o.
      CONCLUSIONS: C. sieberiana roots extract possesses significant antioxidant and
      gastric cytoprotective prostaglandin properties as well as serum secretory
      phospholipase A2 inhibitory activity which could be due to its content of
      polyhydroxy and/or phenolic substances. This may justify its use as an anti
      ulcerogenic agent in traditional medicine in West Africa.

PMID- 22607581
TI  - Head pain referral during examination of the neck in migraine and tension-type
      headache.
AB  - OBJECTIVE: To investigate if and to what extent typical head pain can be
      reproduced in tension-type headache (TTH), migraine without aura sufferers, and
      controls when sustained pressure was applied to the lateral posterior arch of C1
      and the articular pillar of C2, stressing the atlantooccipital and C2-3 segments
      respectively. BACKGROUND: Occipital and neck symptoms often accompany primary
      headache, suggesting involvement of cervical afferents in central pain processing
      mechanisms in these disorders. Referral of head pain from upper cervical
      structures is made possible by convergence of cervical and trigeminal nociceptive
      afferent information in the trigemino-cervical nucleus. Upper cervical segmental
      and C2-3 zygapophysial joint dysfunction is recognized as a potential source of
      noxious afferent information and is present in primary headache sufferers.
      Furthermore, referral of head pain has been demonstrated from symptomatic upper
      cervical segments and the C2-3 zygapophysial joints, suggesting that head pain
      referral may be a characteristic of cervical afferent involvement in headache.
      METHODS: Thirty-four headache sufferers and 14 controls were examined
      interictally. Headache patients were diagnosed according the criteria of the
      International Headache Society and comprised 20 migraine without aura (females n
      = 18; males n = 2; average age 35.3 years) and 14 TTH sufferers (females n = 11;
      males n = 3; average age 30.7 years). Two techniques were used specifically to
      stress the atlantooccipital segments (Technique 1 - C1) and C2-3 zygapophysial
      joints (Technique 2 - C2). Two techniques were also applied to the arm--the
      common extensor origin and the mid belly of the biceps brachii. Participants
      reported reproduction of head pain with "yes" or "no" and rated the intensity of
      head pain and local pressure of application on a scale of 0 -10, where 0 = no
      pain and 10 = intolerable pain. RESULTS: None of the subjects reported head pain
      during application of techniques on the arm. Head pain referral during the
      cervical examination was reported by 8 of 14 (57%) control participants, all TTH
      patients and all but 1 migraineur (P < .002). In each case, participants reported
      that the referred head pain was similar to the pain they usually experienced
      during TTH or migraine. The frequency of head pain referral was identical for
      Techniques 1 and 2. The intensity of referral did not differ between Technique 1
      and Technique 2 or between groups. Tenderness ratings to thumb pressure were
      comparable between the Techniques 1 and 2 when pressure was applied to C1 and C2
      respectively and across groups. Similarly, there were no significant differences
      for tenderness ratings to thumb pressure between Technique 1 and Technique 2 on
      the arm or between groups. While tenderness ratings to thumb pressure for
      Technique 2 were similar for both referral (n = 41) and non-referral (n = 7)
      groups, tenderness ratings for Technique 1 in the referral group were
      significantly greater when compared with the non-referral group (P = .01).
      CONCLUSIONS: Our data support the continuum concept of headache, one in which
      noxious cervical afferent information may well be significantly underestimated.
      The high incidence of reproduction of headache supports the evaluation of
      musculoskeletal features in patients presenting with migrainous and TTH symptoms.
      This, in turn, may have important implications for understanding the
      pathophysiology of headache and developing alternative treatment options.

PMID- 22607582
TI  - High-temperature measurements of the reactions of OH with a series of ketones:
      acetone, 2-butanone, 3-pentanone, and 2-pentanone.
AB  - The overall rate constants for the reactions of hydroxyl radicals (OH) with a
      series of ketones, namely, acetone (CH(3)COCH(3)), 2-butanone (C(2)H(5)COCH(3)),
      3-pentanone (C(2)H(5)COC(2)H(5)), and 2-pentanone (C(3)H(7)COCH(3)), were studied
      behind reflected shock waves over the temperature range of 870-1360 K at
      pressures of 1-2 atm. OH radicals were produced by rapid thermal decomposition of
      the OH precursor tert-butyl hydroperoxide (TBHP) and were monitored by the narrow
      line width ring dye laser absorption of the well-characterized R(1)(5) line in
      the OH A-X (0, 0) band near 306.69 nm. The overall rate constants were inferred
      by comparing the measured OH time histories with the simulated profiles from the
      detailed mechanisms of Pichon et al. (2009) and Serinyel et al. (2010). These
      measured values can be expressed in Arrhenius form as k(CH3COCH3+OH) = 3.30 *
      10(13) exp(-2437/T) cm(3) mol(-1) s(-1), k(C2H5COCH3+OH )= 6.35 * 10(13) exp(
      2270/T) cm(3) mol(-1) s(-1), k(C2H5COC2H5+OH) = 9.29 * 10(13) exp(-2361/T) cm(3)
      mol(-1) s(-1), and k(C3H7COCH3+OH) = 7.06 * 10(13) exp(-2020/T) cm(3) mol(-1) s(
      1). The measured rate constant for the acetone + OH reaction from the current
      study is consistent with three previous experimental studies from Bott and Cohen
      (1991), Vasudevan et al. (2005), and Srinivasan et al. (2007), within +/-20%.
      Here, we also present the first direct high-temperature rate constant
      measurements of 2-butanone + OH, 3-pentanone + OH, and 2-pentanone + OH
      reactions. The measured values for the 2-butanone + OH reaction are in close
      accord with the theoretical calculation from Zhou et al. (2011), and the measured
      values for the 3-pentanone + OH reaction are in excellent agreement with the
      estimates (by analogy with the H-atom abstraction rate constants from alkanes)
      from Serinyel et al. Finally, the structure-activity relationship from Kwok and
      Atkinson (1995) was used to estimate these four rate constants, and the estimated
      values from this group-additivity model show good agreement with the measurements
      (within ~25%) at the present experimental conditions.

PMID- 22607584
TI  - In vivo detection of cortical microinfarcts on ultrahigh-field MRI.
AB  - BACKGROUND AND PURPOSE: Cortical microinfarcts (CMIs) are detected as small foci
      restricted to the cerebral cortex in autopsy brains. CMIs are thought to be
      caused by cerebral amyloid angiopathy (CAA) in the elderly and may be a risk for
      dementia. We aimed to visualize CMIs, which remain invisible on conventional MRI,
      using double inversion recovery (DIR) and 3-dimensional fluid attenuated
      inversion recovery (3D-FLAIR) on 3-Tesla MRI. METHODS: We prospectively performed
      DIR and 3D-FLAIR images in 70 subjects with Alzheimer disease (AD; n = 47), mild
      cognitive impairment (n = 14), AD with cerebrovascular disease (CVD; n = 3),
      vascular dementia (VaD; n = 2), CAA-associated intracerebral hemorrhage (ICH; n =
      2) and one each of normal pressure hydrocephalus and dementia with Lewy bodies
      (DLB). Susceptibility-weighted imaging (SWI) was performed to detect cerebral
      microbleeds (CMBs). RESULTS: Nine subjects (five of AD and one each of AD with
      CVD, ICH, VaD, and DLB) had small intracortical high signal lesions on both DIR
      and 3D-FLAIR images. All the nine subjects accompanied multiple lobar CMBs. These
      intracortical lesions were located in close proximity to CMBs, and were suggested
      to be CMIs. CONCLUSIONS: DIR and 3D-FLAIR images may open a way to visualize
      CMIs.

PMID- 22607585
TI  - Microbeam radiation therapy alters vascular architecture and tumor oxygenation
      and is enhanced by a galectin-1 targeted anti-angiogenic peptide.
AB  - In this study, we sought to determine the therapeutic potential of variably sized
      (50 MUm or 500 MUm wide, 14 mm tall) parallel microbeam radiation therapy (MRT)
      alone and in combination with a novel anti-angiogenic peptide, anginex, in mouse
      mammary carcinomas (4T1)--a moderately hypoxic and radioresistant tumor with
      propensity to metastasize. The fraction of total tumor volume that was directly
      irradiated was approximately 25% in each case, but the distance between segments
      irradiated by the planar microbeams (width of valley dose region) varied by an
      order of magnitude from 150-1500 MUm corresponding to 200 MUm and 2000 MUm center
      to-center inter-microbeam distances, respectively. We found that MRT administered
      in 50 MUm beams at 150 Gy was most effective in delaying tumor growth.
      Furthermore, tumor growth delay induced by 50 MUm beams at 150 Gy was virtually
      indistinguishable from the 500 MUm beams at 150 Gy. Fifty-micrometer beams at the
      lower peak dose of 75 Gy induced growth delay intermediate between 150 Gy and
      untreated tumors, while 500 MUm beams at 75 Gy were unable to alter tumor growth
      compared to untreated tumors. However, the addition of anginex treatment
      increased the relative tumor growth delay after 500 MUm beams at 75 Gy most
      substantially out of the conditions tested. Anginex treatment of animals whose
      tumors received the 50 MUm beams at 150 Gy also led to an improvement in growth
      delay from that induced by the comparable MRT alone. Immunohistochemical staining
      for CD31 (endothelial cells) and alphaSMA (smooth muscle pericyte-associated
      blood vessels as a measure of vessel normalization) indicated that vessel density
      was significantly decreased in all irradiated groups and pericyte staining was
      significantly increased in the irradiated groups on day 14 after irradiation. The
      addition of anginex treatment further decreased the mean vascular density in all
      combination treatment groups and further increased the amount of pericyte
      staining in these tumors. Finally, evidence of tumor hypoxia was found to
      decrease in tumors analyzed at 1-14 days after MRT in the groups receiving 150 Gy
      peak dose, but not 75 Gy peak dose. Our results suggest that tumor vascular
      damage induced by MRT at these potentially clinically acceptable peak entrance
      doses may provoke vascular normalization and may be exploited to improve tumor
      control using agents targeting angiogenesis.

PMID- 22607586
TI  - Combined haploinsufficiency and genetic control of the G2/M checkpoint in
      irradiated cells.
AB  - When cells are exposed to a dose of radiation large enough to cause chromosome
      aberrations, they become arrested at the G(2)/M checkpoint, facilitating DNA
      repair. Defects in checkpoint control genes can impart radiosensitivity. Arrest
      kinetics were monitored in mouse embryo fibroblasts at doses ranging from 10 mGy
      to 5.0 Gy of gamma radiation over a time course of 0 to 12 h. We observe no
      significant checkpoint engagement at doses below 100 mGy. The checkpoint is only
      fully activated at doses where most of the cells are either bound for mitotic
      catastrophe or are reproductively dead. Atm null cells with ablated checkpoint
      function exhibited no robust arrest. Surprisingly, haploinsufficiency for ATM
      alone or in combination with other radioresistance genes did not alter checkpoint
      activation. We have shown previously that haploinsufficiency for several
      radioresistance genes imparts intermediate phenotypes for several end points
      including apoptosis, transformation and survival. These findings suggest that
      checkpoint control does not contribute toward these intermediate phenotypes and
      that different biological processes can be activated at high doses compared to
      low doses.

PMID- 22607588
TI  - The protective layer of biofilm: a repellent function for a new class of
      amphiphilic proteins.
AB  - Bacteria can survive harsh conditions when growing in complex communities of
      cells known as biofilms. The matrix of the biofilm presents a scaffold where
      cells are attached to each other and to the surface. The biofilm matrix is also a
      protective barrier that confers tolerance against various antimicrobial agents.
      In this issue of Molecular Microbiology, Kobayashi and Iwano (2012) show that the
      liquid permeability of Bacillus subtilis biofilms is determined by a small
      secreted protein, i.e. BslA (formerly called YuaB). BslA is important for the
      proper development of biofilms, but unlike exopolysaccharide and TasA, is not
      directly involved in cell cluster formation, and is synthesized following the
      production of exopolysaccharide and amyloid fibres. The amphiphilic BslA protein
      forms a polymer in vitro and localizes in vivo to the surface of the biofilm. The
      microstructures of the biofilm wrinkles are reduced in the bslA mutant strain and
      the liquid repellency of the biofilm surface is diminished. Exogenously added
      BslA(42-181)  protein complements the bslA mutation and restores not only water
      repellency, but also the formation of aerial structures. This study demonstrates
      that amphiphilic proteins have an important role in liquid repellency of biofilms
      and it suggests that these polymers contribute to antimicrobial resistance.

PMID- 22607587
TI  - An eQTL biological data visualization challenge and approaches from the
      visualization community.
AB  - In 2011, the IEEE VisWeek conferences inaugurated a symposium on Biological Data
      Visualization. Like other domain-oriented Vis symposia, this symposium's purpose
      was to explore the unique characteristics and requirements of visualization
      within the domain, and to enhance both the Visualization and Bio/Life-Sciences
      communities by pushing Biological data sets and domain understanding into the
      Visualization community, and well-informed Visualization solutions back to the
      Biological community. Amongst several other activities, the BioVis symposium
      created a data analysis and visualization contest. Unlike many contests in other
      venues, where the purpose is primarily to allow entrants to demonstrate tour-de
      force programming skills on sample problems with known solutions, the BioVis
      contest was intended to whet the participants' appetites for a tremendously
      challenging biological domain, and simultaneously produce viable tools for a
      biological grand challenge domain with no extant solutions. For this purpose
      expression Quantitative Trait Locus (eQTL) data analysis was selected. In the
      BioVis 2011 contest, we provided contestants with a synthetic eQTL data set
      containing real biological variation, as well as a spiked-in gene expression
      interaction network influenced by single nucleotide polymorphism (SNP) DNA
      variation and a hypothetical disease model. Contestants were asked to elucidate
      the pattern of SNPs and interactions that predicted an individual's disease
      state. 9 teams competed in the contest using a mixture of methods, some
      analytical and others through visual exploratory methods. Independent panels of
      visualization and biological experts judged entries. Awards were given for each
      panel's favorite entry, and an overall best entry agreed upon by both panels.
      Three special mention awards were given for particularly innovative and useful
      aspects of those entries. And further recognition was given to entries that
      correctly answered a bonus question about how a proposed "gene therapy" change to
      a SNP might change an individual's disease status, which served as a calibration
      for each approaches' applicability to a typical domain question. In the future,
      BioVis will continue the data analysis and visualization contest, maintaining the
      philosophy of providing new challenging questions in open-ended and dramatically
      underserved Bio/Life Sciences domains.

PMID- 22607592
TI  - What is your diagnosis? 12-year-old spayed female Labrador Retriever with a
      history of polyuria and polydipsia.

PMID- 22607593
TI  - What is your diagnosis? 3-year-old neutered male Burmese cat with a 3-month
      history of nonspecific hind limb gait abnormalities.

PMID- 22607594
TI  - Pathology in practice. 3-week-old female Suffolk lamb with a large perianal mass.

PMID- 22607595
TI  - Effect of anesthetic breathing circuit type on thermal loss in cats during
      inhalation anesthesia for ovariohysterectomy.
AB  - OBJECTIVE: To compare the effects of a nonrebreathing circuit versus a reduced
      volume circle anesthetic breathing circuit on body temperature change in cats
      during inhalation anesthesia for ovariohysterectomy. DESIGN: Randomized,
      controlled clinical trial. ANIMALS: 141 female domestic cats hospitalized for
      routine ovariohysterectomy. PROCEDURES: Cats were randomly assigned to receive
      inhalation anesthetics from either a nonrebreathing circuit or a reduced volume
      circle system with oxygen flow rates of 200 and 30 mL/kg/min (90.9 and 13.6
      mL/lb/min), respectively. Body temperatures were monitored throughout the
      anesthetic period via an intrathoracic esophageal probe placed orally into the
      esophagus to the level of the heart base. RESULTS: No difference in body
      temperature was found between the 2 treatment groups at any measurement time. The
      duration of procedure had a significant effect on body temperature regardless of
      the type of anesthetic circuit used. CONCLUSIONS AND CLINICAL RELEVANCE: Duration
      of the procedure rather than the type of anesthetic circuit used for inhalation
      anesthesia was more influential on thermal loss in cats undergoing
      ovariohysterectomy.

PMID- 22607596
TI  - Incidence of intervertebral disk degeneration-related diseases and associated
      mortality rates in dogs.
AB  - OBJECTIVE: To determine the incidence and distribution of intervertebral disk
      (IVD) degeneration-related diseases in a large population of dogs of various
      breeds, ages, and sexes and to determine mortality rates among dogs with these
      diseases. DESIGN: Epidemiological study. SAMPLE: Insurance data for dogs with
      veterinary health-care and life insurance coverage (n = 665,249 and 552,120,
      respectively). PROCEDURES: Insurance claim records of 1 company in Sweden were
      searched to identify dogs with IVD degeneration-related diseases; incidence and
      mortality rates were determined for affected dogs < 12 years old and < 10 years
      old, respectively. Only the first paid IVD degeneration-related claim for a dog
      was included in incidence rate calculations. RESULTS: The incidence rate of IVD
      degeneration-related diseases was 27.8 (95% confidence interval [CI], 27.2 to
      28.4) occurrences/10,000 dog-years at risk (DYAR), indicating that approximately
      0.3% of dogs/y in this population were affected. Miniature Dachshund was the most
      highly represented breed, followed by Standard Dachshund and Doberman Pinscher
      (237.1 [95% CI, 212.9 to 261.4], 141.5 [95% CI, 135.5 to 147.4], and 88.6 [95%
      CI, 72.1 to 105.2] occurrences/10,000 DYAR, respectively). The incidence rate of
      IVD degeneration-related disease was greater in male than in female dogs and
      increased with age. Overall mortality rate attributed to IVD degeneration-related
      diseases was 9.4 (95% CI, 8.9 to 9.8) deaths/10,000 DYAR and was greater in males
      than in females. CONCLUSIONS AND CLINICAL RELEVANCE: Differences in incidence
      rates among various breeds suggested a genetic involvement. Knowledge of the
      distribution of IVD degeneration-related diseases among dogs of various breeds
      and ages may facilitate early diagnosis and preemptive treatments in patients at
      risk for developing these diseases.

PMID- 22607597
TI  - Use of samarium Sm 153 lexidronam for the treatment of dogs with primary tumors
      of the skull: 20 cases (1986-2006).
AB  - OBJECTIVE: To evaluate samarium Sm 153 lexidronam ((153)Sm-EDTMP) as a treatment
      option for dogs with bony tumors of the skull. DESIGN: Retrospective case series.
      ANIMALS: Dogs with multilobular osteochondrosarcoma (MLO) or osteosarcoma (OSA)
      of the skull. PROCEDURES: Veterinary Medical Teaching Hospital records from the
      Universities of Missouri and Florida from 1986 to 2006 were searched for dogs
      with primary skull tumors treated with (153)Sm-EDTMP. RESULTS: 25 dogs were
      initially evaluated, with 5 dogs subsequently excluded because of inadequate
      follow-up or unrelated death. Seven OSAs and 13 MLOs were diagnosed. Tumors
      involved the occipital and frontal bones (n = 10), zygomatic arch and maxilla
      region (6), palate (3), and mandible (1). No clinically important adverse effects
      related to (153)Sm-EDTMP treatment were documented. Of the 20 dogs evaluated 21
      days after injection with (153)Sm-EDTMP, 4 had subjective improvement, 13 had
      progressive disease, and 3 had insufficient follow-up. On the basis of
      radiographic findings, metastasis was suspected in 1 dog; 16 dogs had no
      metastasis evident, and medical records were insufficient for 3 dogs. Survival
      time, defined as the (153)Sm-EDTMP injection date to the date of death, ranged
      from 3 to 1,314 days (median, 144 days). CONCLUSIONS AND CLINICAL RELEVANCE: The
      subjective improvement in 4 patients and lack of clinical evidence of adverse
      effects suggested that (153)Sm-EDTMP injection may be an option for the treatment
      of dogs with MLO or OSA of the skull when other treatments have failed or surgery
      is not possible.

PMID- 22607598
TI  - Rapid prototype modeling and customized titanium plate fabrication for correction
      of a persistent hard palate defect in a dog.
AB  - CASE DESCRIPTION: An 8-month-old crossbred dog was evaluated because of an
      oronasal fistula following 2 previous attempts to surgically correct a secondary
      palate defect. CLINICAL FINDINGS: Three months after initial evaluation and
      successful closure of the soft palate section of the secondary palate defect via
      2 surgeries, an oronasal fistula was present. The oronasal fistula was
      predominantly right sided, involving the rostral third of the hard palate and, at
      the widest aspect, spanning the transverse palate at the level of the maxillary
      canine teeth. TREATMENT AND OUTCOME: Following CT of the rostral aspect of the
      skull, rapid prototyping technology was used to create a stereolithographic model
      of the skull, allowing fabrication of a customized titanium plate for intranasal
      stenting. The titanium plate was inserted via a rostral nasal approach and
      secured rostrally with 1.5-mm screws and caudally with 2.4-mm screws from the
      nasal bridge. An oronasal fistula formed laterally at the edge of the plate, but
      bonding of a dental glass ionomer product resulted in successful resolution of
      the fistula. CLINICAL RELEVANCE: Results suggested that rapid prototyping and
      creation of customized implants may provide an option for the management of large
      or nonreconstructible oronasal defects in dogs.

PMID- 22607600
TI  - Use of zoledronate for treatment of a bone fragility disorder in horses.
AB  - OBJECTIVE: To assess clinical outcomes and scintigraphic findings in horses with
      a bone fragility disorder (BFD) treated with zoledronate (a nitrogen-containing
      bisphosphonate). DESIGN: Prospective uncontrolled clinical trial. ANIMALS: 10
      horses with evidence of a BFD. PROCEDURES: Signalment, history, and geographic
      location of horses' home environments were recorded. Physical examinations,
      lameness evaluations, and nuclear scintigraphy were performed. Diagnosis of a BFD
      was made on the basis of results of clinical and scintigraphic examination. Each
      horse was treated with zoledronate (0.075 mg/kg [0.034 mg/lb, IV, once]) at the
      time of diagnosis. Horses were reevaluated 6 months after treatment. RESULTS:
      Affected horses were from the central and coastal regions of California and had
      >= 1 clinical sign of the disorder; these included scapular deformation (n = 2),
      lordosis (1), nonspecific signs of musculoskeletal pain (1), and lameness that
      could not be localized to a specific anatomic region (9). All horses had multiple
      sites of increased radiopharmaceutica uptake during initial scintigraphic
      evaluation of the axial skeleton and bones of 1 or both forelimbs. Six months
      after treatment, clinical improvement (defined as improvement in the lameness
      score, resolution of signs of musculoskeletal pain, or both) was detected in 9 of
      10 horses; scintigraphic uptake was unchanged (n = 2) or subjectively decreased
      (8). No adverse effects attributed to zoledronate treatment were detected.
      CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with zoledronate appeared to be
      useful in improving clinical outcome and scintigraphic findings in horses with a
      BFD; however, future placebo-controlled studies are necessary to accurately
      determine efficacy and long-term safety.

PMID- 22607601
TI  - Investigation of an outbreak of besnoitiosis in donkeys in northeastern
      Pennsylvania.
AB  - OBJECTIVE: To describe the clinical, endoscopic, and serologic features of an
      outbreak of besnoitiosis in 2 donkey operations in northeastern Pennsylvania and
      to report the outcome of attempted treatment of 1 naturally infected individual.
      DESIGN: Observational study. ANIMALS: 29 donkeys (Equus asinus) in northeastern
      Pennsylvania. PROCEDURES: Donkeys were examined for lesions suggestive of
      besnoitiosis in an outbreak investigation. Information was collected regarding
      the history and signalment of animals on each premises. Rhinolaryngoscopy was
      performed to identify nasopharyngeal and laryngeal lesions. Serum samples were
      collected for immunofluorescent antibody testing and immunoblotting for Besnoitia
      spp. Skin biopsy samples were obtained from 8 animals with lesions suggestive of
      besnoitiosis for histologic examination. Quantitative real-time PCR assay for
      Besnoitia spp was performed on tissue samples from 5 animals. RESULTS:
      Besnoitiosis was confirmed in 6 of the 8 suspected cases. The most common lesion
      site was the nares, followed by the skin and sclera. Donkeys with clinical signs
      of disease had higher serum antibody titers and tested positive for a greater
      number of immunoblot bands than did donkeys without clinical signs of disease.
      All animals evaluated by PCR assay tested positive. Putative risk factors for
      disease included age and sex. Ponazuril was not effective at treating
      besnoitiosis in a naturally infected donkey. CONCLUSIONS AND CLINICAL RELEVANCE:
      Knowledge of clinical and serologic features of besnoitiosis in donkeys will
      assist clinicians in the diagnosis and prevention of this disease in donkey
      populations. Besnoitiosis may be an emerging disease of donkeys in the United
      States.

PMID- 22607602
TI  - Results of computed tomography in horses with ethmoid hematoma: 16 cases (1993
      2005).
AB  - OBJECTIVE: To determine whether CT provides unique information about the
      treatment or prognosis for horses with ethmoid hematoma (EH). DESIGN:
      Retrospective case series. ANIMALS: 16 horses with EH. PROCEDURES: Horses with a
      diagnosis of EH that had undergone a diagnostic CT study were included. Clinical
      features, treatment, outcome, radiographic and CT images, and histologic
      specimens were reviewed. RESULTS: CT provided new diagnostic information that
      affected treatment in 10 of 16 horses. Bilateral disease occurred in 8 of 16
      horses and was undetected in 5 horses prior to CT. Paranasal sinus involvement
      occurred in all horses, but was incompletely defined prior to CT in 7 of 16
      horses. The sphenopalatine sinus was affected in 6 of 16 horses as detected on
      CT; 4 of 6 of these were bilaterally affected. Medical and surgical treatments
      were performed. Six of 10 horses had a successful outcome, with recurrence in 4
      of 10. Five of 6 patients in which treatment addressed all lesion sites
      identified by CT had a successful outcome. Bilateral disease did not confer a
      poor prognosis when all affected sites were treated. Sphenopalatine sinus
      involvement may have been associated with recurrence. CONCLUSIONS AND CLINICAL
      RELEVANCE: CT provided anatomic information that may facilitate effective
      treatment of horses with EH, particularly in patients with bilateral disease and
      paranasal sinus involvement. Computed tomography is recommended for patients in
      which the lesion cannot be viewed endoscopically, when sinus involvement or
      multifocal disease are suspected, or when the lesion has been unresponsive to
      treatment.

PMID- 22607603
TI  - Frequency of use and proficiency in performance of surgical skills expected of
      entry-level veterinarians by general practitioners.
AB  - OBJECTIVE: To identify a list of core surgical skills and determine the frequency
      of use and proficiency in performance of these skills expected of entry-level
      veterinarians by general practitioners. DESIGN: Mail-based survey. SAMPLE: 750
      general practitioners randomly chosen from the AVMA membership database.
      PROCEDURES: Survey respondents rated the proficiency and frequency of use
      expected of entry-level veterinarians in regard to 26 surgical skills.
      Demographic information (gender; graduation year; practice type, geographic
      location, and setting; number of veterinarians in practice; number of surgical
      procedures performed per week; and number of new graduates mentored in the past 5
      years) of respondents was obtained. RESULTS: 387 (52%) general practitioners
      responded to the survey. Greater than 60% of respondents expected new graduates
      to have high proficiency and require minimal supervision for 21 of 26 skills.
      Greater than 60% of respondents assigned 6 of the skills a low expected frequency
      of use rating. Orthopedic skills, creation of square knots by use of a 1-handed
      tie technique, and use of electrosurgical and laser instruments received some of
      the lowest ratings. CONCLUSIONS AND CLINICAL RELEVANCE: Core surgical skills were
      identified. Results indicated a broad consensus among general practitioners
      independent of demographic characteristics. Results may aid veterinary colleges
      in identification of the surgical skills that are most important to include in
      surgical curricula and for which new graduates should attain proficiency
      according to general practitioners.

PMID- 22607604
TI  - Selective photoreduction of nitric oxide to nitrogen by nanostructured TiO2
      photocatalysts: role of oxygen vacancies and iron dopant.
AB  - Conventional TiO(2)-based photocatalysts oxidize NO(x) to nitrate species, which
      do not spontaneously desorb and therefore deactivate the catalyst. We show that
      the selectivity of this reaction can be changed by creating a large concentration
      of oxygen vacancies in TiO(2) nanoparticles through thermal reduction in a
      reducing atmosphere. This results in the photoreduction of nitric oxide (NO) to
      N(2) and O(2), species which spontaneously desorb at room temperature. The
      activity of the photoreduction reaction can be greatly enhanced by doping the
      TiO(2) nanoparticles with Fe(3+), an acceptor-type dopant that stabilizes the
      oxygen vacancies. Moreover, the photoinduced reduction of Fe(3+) to Fe(2+)
      provides a recombination pathway that almost completely suppresses the formation
      of NO(2) and thus enhances the selectivity of the reaction for N(2) formation.
      Gas chromatography confirms that N(2) and O(2) are formed in a stoichiometric
      ratio, and the activity for NO decomposition is found to be limited by the
      concentration of oxygen vacancies. A series of internally consistent reaction
      equations are proposed that describe all experimentally observed features of the
      photocatalytic process. The observed influence of oxygen vacancies on the
      activity and selectivity of photoinduced reactions may lead to new routes toward
      the design of highly selective photocatalysts.

PMID- 22607605
TI  - Abstracts Albany 2003 The 13th Conversation.

PMID- 22607607
TI  - Comparison of blood dynamics of anticancer drugs (cisplatin, mitomycin C,
      epirubicin) in treatment groups of hepatic arterial infusion, hepatic arterial
      infusion with lipiodol and transcatheter arterial chemoembolization with lipiodol
      plus gelatin sponge particles in a swine model.
AB  - AIM:   To compare the blood dynamics of anticancer drugs (cisplatin, mitomycin,
      epirubicin) and the negative effect on normal liver tissue among the following
      procedures: hepatic arterial infusion (HAI), HAI with lipiodol (Lp-HAI) and
      transcatheter arterial chemoembolization (TACE) with Lp plus particles (Lp-TACE).
      METHODS:   Nine swine were divided into three groups: (i) HAI group animals were
      infused with 5 mg/mL cisplatin, 1 mg/mL mitomycin and 4 mg/mL epirubicin in 0.1
      mL/kg contrast medium; (ii) Lp-HAI group animals, with the same doses in 0.1 mL
      emulsified fluid (0.05 mL/kg, Lp); and (iii) Lp-TACE group animals, with the same
      doses in 0.1 mL emulsified fluid plus gelatin sponge particles. Outflow ratio
      (area under plasma concentration curve [AUC(0-60) ] / total infused dose of
      anticancer drug) and necrosis volume ratio (necrosis volume / total slice volume
      * 100) were explored. RESULTS:   Outflow ratios (AUC(0-60) /mg) of cisplatin,
      mitomycin and epirubicin, and the necrosis volume ratio (%) of the livers, were
      2.30, 6.91, 0.97 and 0, respectively, in the HAI group; 1.71, 5.43, 0.79 and
      1.37, respectively, in the Lp-HAI group; and 1.23, 3.37, 0.47 and 20.88,
      respectively, in the Lp-TACE group. The significantly lowest outflow ratio for
      each anticancer drug (P = 0.05/3) and the significantly highest necrosis volume
      ratio (P = 0.05/3) were found in Lp-TACE, followed by Lp-HAI and HAI. CONCLUSION:
      Although the necrosis volume ratio of the liver was tolerable, Lp-TACE caused
      the greatest delay in outflow ratio for each cancer drug and the greatest
      negative effect to liver in a swine model.

PMID- 22607606
TI  - Provision of dental care in aged care facilities, NSW, Australia - part 1 as
      perceived by the directors of nursing (care providers).
AB  - OBJECTIVE: To ascertain the Directors of Nursing (DONs) perception of the
      provision of dental care and the difficulties in oral health maintenance for
      residents in New South Wales (NSW) aged care facilities (ACFs). BACKGROUND: There
      were no specific figures relating to DONs' perceptions of oral health needs and
      dental care nor obstructions to dental care of residents. MATERIALS AND METHODS:
      A total of 414 questionnaires, encoded for confidentiality, were posted to all
      DONs of ACFs in NSW and the data analysed. RESULTS: Questionnaires were returned
      from 255 ACFs (response rate 61.6%) representing 16 861 residents with a male-to
      female ratio of 1:3.45. Of these residents, 48% had a dental assessment on
      admission by qualified dental staff. In 74.2% of facilities, no regular visits by
      dental staff took place, and 58.6% considered the perceived unwillingness of
      dental professionals to visit residents a barrier to good oral health. DONs
      reported that 53.6% of residents had dentures only, while 18.3% had natural teeth
      only. The most frequent difficulties reported by staff were residents' use of
      abusive language (78.2%) and residents refusing to open mouth (60.9%).
      CONCLUSION: Lack of involvement of dental professionals in admission assessment
      and in ongoing programmes was of concern to DONs in ACFs.

PMID- 22607608
TI  - Impact of different ionization methods on the molecular assignments of
      asphaltenes by FT-ICR mass spectrometry.
AB  - Over the years, ultrahigh resolution mass spectrometry has successfully
      illustrated the extreme complexity of crude oil and related solubility or
      polarity based fractions on a molecular level. However, the applied ionization
      technique greatly influences the outcome and may provide misleading information.
      In this work, we investigate the atmospheric pressure laser ionization (APLI)
      technique coupled with Fourier transform ion cyclotron resonance mass
      spectrometer to analyze the asphaltene fraction of a crude oil. These results
      were compared to data obtained by using other existing atmospheric pressure
      ionization methods. Furthermore elemental analysis and solid state NMR were used
      to obtain the bulk characteristics of the asphaltene sample. The results of the
      different ionization techniques were compared with the bulk properties in order
      to describe the potential discrimination effects of the ionization techniques
      that were observed. The results showed that APLI expands the range of the
      assigned molecules, while retaining information already observed with the
      generally used ion sources.

PMID- 22607611
TI  - Clinical, haematological and biochemical responses of sheep undergoing autologous
      blood transfusion.
AB  - BACKGROUND: This study aimed to evaluate the clinical, haematological and
      biochemical responses to autologous blood transfusion and the feasibility of this
      practice in sheep. Thus, we used eight male, 8 months old sheep, weighing on
      average 30 kg, from which 15 mL/kg of whole blood was collected and stored in
      CPDA-1 bags. Blood samples were refrigerated for 8 days and subsequently re
      infused. The clinical, haematological and biochemical parameters were evaluated
      before blood collection and reinfusion, after 10 minutes of collection and
      reinfusion, after 3, 6, 12, 24, 48, 96 and 192 hours after collection and
      reinfusion. RESULTS: With respect to clinical parameters, we observed a decrease
      in heart rate after 24, 48 and 196 hours from reinfusion compared to basal values
      (p < 0.05). Haematological variables including globular volume and erythrocyte
      counts showed a significant decrease (p < 0.01) at all time points after
      collection and increased (p < 0.01) at all time points after reinfusion. There
      was a significant increase in total protein and calcium at all time points after
      reinfusion (p < 0.05). CONCLUSION: Autologous transfusion in sheep slightly
      altered the physiological, biochemical and haematological responses of sheep,
      indicating that the technique proposed is safe and can be applied in the clinical
      practice of this species. The 8 d period was not sufficient for complete recovery
      of the haematological parameters after blood collection.

PMID- 22607609
TI  - Up-regulation of microglial cathepsin C expression and activity in
      lipopolysaccharide-induced neuroinflammation.
AB  - BACKGROUND: Cathepsin C (Cat C) functions as a central coordinator for activation
      of many serine proteases in inflammatory cells. It has been recognized that Cat C
      is responsible for neutrophil recruitment and production of chemokines and
      cytokines in many inflammatory diseases. However, Cat C expression and its
      functional role in the brain under normal conditions or in neuroinflammatory
      processes remain unclear. Our previous study showed that Cat C promoted the
      progress of brain demyelination in cuprizone-treated mice. The present study
      further investigated the Cat C expression and activity in lipopolysaccharide
      (LPS)-induced neuroinflammation in vivo and in vitro. METHODS: C57BL/6 J mice
      were intraperitoneally injected with either 0.9% saline or lipopolysaccharide
      (LPS, 5 mg/kg). Immunohistochemistry (IHC) and in situ hybridization (ISH) were
      used to analyze microglial activation, TNF-alpha, IL-1beta, IL-6, iNOS mRNAs
      expressions and cellular localization of Cat C in the brain. Nitrite assay was
      used to examine microglial activation in vitro; RT-PCR and ELISA were used to
      determine the expression and release of Cat C. Cat C activity was analyzed by
      cellular Cat C assay kit. Data were evaluated for statistical significance with
      paired t test. RESULTS: Cat C was predominantly expressed in hippocampal CA2
      neurons in C57BL/6 J mice under normal conditions. Six hours after LPS injection,
      Cat C expression was detected in cerebral cortical neurons; whereas, twenty-four
      hours later, Cat C expression was captured in activated microglial cells
      throughout the entire brain. The duration of induced Cat C expression in neurons
      and in microglial cells was ten days and three days, respectively. In vitro, LPS,
      IL-1beta and IL-6 treatments increased microglial Cat C expression in a dose
      dependent manner and upregulated Cat C secretion and its activity. CONCLUSIONS:
      Taken together, these data indicate that LPS and proinflammatory cytokines IL
      1beta, IL-6 induce the expression, release and upregulate enzymatic activity of
      Cat C in microglial cells. Further investigation is required to determine the
      functional role of Cat C in the progression of neuroinflammation, which may have
      implications for therapeutics for the prevention of neuroinflammation-involved
      neurological disorders in the future.

PMID- 22607610
TI  - Predictors and outcome of patients with acute respiratory distress syndrome
      caused by miliary tuberculosis: a retrospective study in Chongqing, China.
AB  - BACKGROUND: Miliary tuberculosis (TB) is an uncommon cause of acute respiratory
      distress syndrome (ARDS) with a high mortality. The aim of the present study was
      to evaluate the clinical characteristics, predictors and outcome of patients with
      ARDS caused by miliary TB. METHODS: A retrospective study was conducted among
      patients with a diagnosis of ARDS with miliary TB in four hospitals from 2006 to
      2010. Medical records and laboratory examinations of these patients were taken
      during the first 24 h of admission. RESULTS: Eighty-five patients with miliary TB
      developed ARDS, 45 of whom survived (52.9%). The median age was 36.6 +/- 12.5
      years with 38 males (44.7%). Diabetes mellitus (DM) was the most common
      underlying disease (18.8%).ICU mortality was 47.1%. The time from admission to
      anti-tuberculosis therapy was 4.5 +/- 2.0 days. Mean duration of mechanical
      ventilation was 8.5 +/- 3.0 days in all patients. Duration of time to diagnosis,
      time from diagnosis to mechanical ventilation, and time to anti-tuberculosis
      therapy were significantly shorter in survivors than those in non-survivors.
      Diabetes mellitus (OR 5.431, 95%CI 1.471-20.049; P = 0.005), ALT (70-100U/L, OR
      10.029, 95%CI 2.764-36.389; P = 0.001), AST (>94U/L,OR 8.034, 95%CI 2.200-29.341;
      P = 0.002), D-dimer (>1.6mg/L, OR 3.167, 95%CI 0.896-11.187; P = 0.042),
      hemoglobin (<90g/L, OR 14.824, 95%CI 3.713-59.179; P = 0.001), albumin (<25g/L,
      OR 15.896, 95%CI 3.975-63.566; P = 0.001) were independent predictors of ARDS
      development in the setting of miliary TB. CONCLUSIONS: Accurate diagnosis, early
      initiation of anti-tuberculosis therapy and mechanical ventilation are important
      for the outcome of patients with ARDS caused by miliary TB. DM, ALT, AST, D
      dimer, hemoglobin, and albumin are independent predictors of ARDS development in
      patients with miliary TB.

PMID- 22607612
TI  - Axillary lymph node dose with tangential whole breast radiation in the prone
      versus supine position: a dosimetric study.
AB  - BACKGROUND: Prone breast positioning reduces skin reaction and heart and lung
      dose, but may also reduce radiation dose to axillary lymph nodes (ALNs). METHODS:
      Women with early stage breast cancer treated with whole breast irradiation (WBI)
      in the prone position were identified. Patients treated in the supine position
      were matched for treating physician, laterality, and fractionation. Ipsilateral
      breast, tumor bed, and Level I, II, and III ALNs were contoured according to the
      RTOG breast atlas. Clips marking surgically removed sentinel lymph nodes (SLN)s
      were contoured. Treatment plans developed for each patient were retrospectively
      analyzed. V90% and V95% was calculated for each axillary level. When present,
      dose to axillary surgical clips was calculated. RESULTS: Treatment plans for 46
      women (23 prone and 23 supine) were reviewed. The mean V90% and V95% of ALN Level
      I was significantly lower for patients treated in the prone position (21% and
      14%, respectively) than in the supine position (50% and 37%, respectively) (p <
      0.0001 and p < 0.0001, respectively). Generally, Level II & III ALNs received
      little dose in either position. Sentinel node biopsy clips were all contained
      within axillary Level I. The mean V95% of SLN clips was 47% for patients treated
      in the supine position and 0% for patients treated in the prone position (p <
      0.0001). Mean V90% to SLN clips was 96% for women treated in the supine position
      but only 13% for women treated in the prone position. CONCLUSIONS: Standard
      tangential breast irradiation in the prone position results in substantially
      reduced dose to the Level I axilla as compared with treatment in the supine
      position. For women in whom axillary coverage is indicated such as those with
      positive sentinel lymph node biopsy who do not undergo completion axillary
      dissection, treatment in the prone position may be inappropriate.

PMID- 22607613
TI  - Extended release formulations for local anaesthetic agents.
AB  - Systemic toxicity through overdose of local anaesthetic agents is a real concern.
      By encapsulating local anaesthetics in biodegradable carriers to produce a system
      for prolonged release, their duration of action can be extended. This
      encapsulation should also improve the safety profile of the local anaesthetic as
      it is released at a slower rate. Work with naturally occurring local
      anaestheticss has also shown promise in the area of reducing systemic and
      neurotoxicity. Extended duration local anaesthetic formulations in current
      development or clinical use include liposomes, hydrophobic based polymer
      particles such as Poly(lactic-co-glycolic acid) microspheres, pasty injectable
      and solid polymers like Poly(sebacic-co-ricinoleic acid) P(SA:RA) and their
      combination with synthetic and natural local anaesthetic. Their duration of
      action, rationale and limitations are reviewed. Direct comparison of the
      different agents is limited by their chemical properties, the drug doses
      encapsulated and the details of in vivo models described.

PMID- 22607614
TI  - Late diagnosis of HIV infection in Brazil despite over 15 years of free and
      universal access to treatment.

PMID- 22607615
TI  - A strain of piscine myocarditis virus infecting Atlantic argentine, Argentina
      silus (Ascanius).

PMID- 22607616
TI  - Etching processes of polytetrafluoroethylene surfaces exposed to He and He-O2
      atmospheric post-discharges.
AB  - A comparative study of polytetrafluoroethylene (PTFE) surfaces treated by the
      post-discharge of He and He-O(2) plasmas at atmospheric pressure is presented.
      The characterization of treated PTFE surfaces and the species involved in the
      surface modification are related. In pure He plasmas, no significant change of
      the surface has been observed by X-ray photoelectron spectroscopy (XPS), dynamic
      water contact angles (dWCA) and atomic force microscopy (AFM), in spite of
      important mass losses recorded. According to these observations, a layer-by-layer
      physical etching without any preferential orientation is proposed, where the
      highly energetic helium metastables are the main species responsible for the
      scission of -(CF(2))(n)- chains. In He-O(2) plasmas, as the density of helium
      metastables decreases as a function of the oxygen flow rate, the treatment leads
      to fewer species ejected from the PTFE surfaces (in agreement with mass loss
      measurements and the detection of fluorinated species onto aluminum foil).
      However, the dWCA and AFM measurements show an increase in the hydrophobicity and
      the roughness of the surface. The observed alveolar structures are assumed to be
      caused by an anisotropic etching where the oxygen atoms etch mainly the amorphous
      phase.

PMID- 22607617
TI  - Scleromyxoedema with disseminated subcutaneous nodules: rare presentation of an
      uncommon dermatosis.
AB  - Scleromyxoedema, also known as generalized lichen myxoedematosus, is a cutaneous
      mucinosis characterized by a generalized papular and sclerodermoid eruption,
      mucin deposition, increased fibroblast proliferation and fibrosis. It is often
      associated with underlying monoclonal gammopathy, and it responds poorly to
      treatment. There are very few reports of nodular eruption in scleromyxoedema. We
      report a case of a prominent nodular eruption in an adolescent boy with
      scleromyxoedema without any underlying paraproteinaemia, and review the
      literature.

PMID- 22607618
TI  - Reducing medication regimen complexity for older patients prior to discharge from
      hospital: feasibility and barriers.
AB  - WHAT IS KNOWN AND OBJECTIVE: Older hospital inpatients are often prescribed
      complex multi-drug regimens; increased regimen complexity is associated with
      poorer medication adherence and treatment outcomes. There has been little
      research into methods for reducing regimen complexity. The objective of this
      study was to explore the feasibility of incorporating medication regimen
      simplification into routine clinical pharmacist care for older hospital
      inpatients and identify barriers to regimen simplification at a major teaching
      hospital. METHODS: Following an educational intervention, clinical pharmacists
      were encouraged to minimize regimen complexity for their patients by identifying
      potential simplifications during routine medication regimen reviews (e.g.
      medication chart reviews, discharge prescription reviews) and discussing these
      changes with hospital doctors and patients. Pharmacists completed a data
      collection form for patients aged 60 years or above discharged from their wards
      during the study period (n = 205; mean age, 81.3 years), indicating whether they
      had reviewed the patient's medication regimen complexity (and if not why),
      whether any changes to simplify the regimen were identified, and whether changes
      were successfully implemented (and if not why). RESULTS AND DISCUSSION:
      Pharmacists reviewed medication regimen complexity for 173/205 (84.4%) patients
      and identified 149 potential changes to reduce regimen complexity for 79/173
      (45.7%) reviewed patients. Ninety-four (63.1%) changes were successfully
      implemented in 54/205 (26.3%) patients. Regimens were simplified more often for
      patients discharged from subacute aged care (geriatric assessment and
      rehabilitation) wards compared with acute general medicine wards. The most
      commonly cited reason for not reviewing regimen complexity and not implementing
      identified simplification-related changes was 'lack of time'. Non-acceptance of
      pharmacist recommendations by patients or doctors were other common reasons for
      not implementing changes. WHAT IS NEW AND CONCLUSION: This is the first study to
      explore pharmacist-led medication regimen simplification and barriers to regimen
      simplification in the hospital setting. It demonstrates that simplification of
      older inpatients' regimens is feasible when training in regimen simplification is
      provided. The main barrier to regimen simplification appears to be lack of
      pharmacist time.

PMID- 22607621
TI  - Profile-QSAR and Surrogate AutoShim protein-family modeling of proteases.
AB  - The 2D Profile-QSAR and 3D Surrogate AutoShim protein-family virtual screening
      methods were originally developed for kinases. They are the key components of an
      iterative medium-throughput screening alternative to expensive and time-consuming
      experimental high-throughput screening. Encouraged by the success with kinases,
      the S1-serine proteases were selected as a second protein family to tackle, based
      on the structural and SAR similarity among them, availability of structural and
      bioactivity data, and the current and future small-molecule drug discovery
      interest. A validation study on 24 S1-serine protease assay data sets from 16
      unique proteases gave very promising results. Profile-QSAR gave a median R(ext)2
      = 0.60 for 24 assay data sets, and pairwise selectivity modeling on 60 protease
      pairs gave a median R(ext)2 = 0.64, comparable to the performance for kinases. A
      17-structure universal ensemble S1-serine protease surrogate receptor for
      Autoshim was developed from a collection of ~1500 X-ray structures. The
      predictive performance on 24 S1-serine protease assays was good, with a median
      R(ext)2 = 0.41, but lower than had been obtained for kinases. Analysis suggested
      that the higher structural diversity of the protease structures, as well as
      smaller assay data sets and fewer potent compounds, both contributed to the
      decreased predictive power. In a prospective virtual screening application, 32
      compounds were ordered from a 1.5 million archive and tested in a biochemical
      assay. Thirteen of the 32 compounds were active at IC50 <= 10 MUM, a 41% hit
      rate. Three new scaffolds were identified which are being followed up with
      testing of additional analogues. A SAR similarity analysis for this target
      against 13 other proteases also indicated two potential protease targets which
      were positively and negatively correlated with the activity of the target
      protease.

PMID- 22607622
TI  - Dietary resveratrol increases the expression of hepatic 7alpha-hydroxylase and
      ameliorates hypercholesterolemia in high-fat fed C57BL/6J mice.
AB  - BACKGROUND: Resveratrol (RSV), a naturally occurring polyphenolic stilbenoid, is
      known to possess potent anti-atherogenic properties; however, the effect of RSV
      on hypercholesterolemia is not fully understood. We hypothesized that RSV
      decreases blood cholesterol levels through the activation of cholesterol 7alpha
      hydroxylase (CYP7A1)-mediated bile acid synthetic pathway pathways in vitro and
      in vivo. METHODS: In this study, we evaluated body weight, serum lipid
      concentrations, hepatic lipid content and the size of the bile acid pool in high
      fat diet (HFD)-fed C57BL/6 J mice that were treated with RSV. In addition, we
      characterized the underlying mechanism of the effects of RSV in HepG2 hepatocytes
      by Western blot analysis. RESULTS: RSV (200 mg/kg per day) reduced body weight
      and liver weight gains, improved serum lipid parameters, reduced hepatic
      cholesterol accumulation and increased the bile acid pool size in mice fed an HFD
      for 8 wks. RSV significantly increased liver expression of CYP7A1 mRNA and
      protein and CYP7A1 enzyme activity. Furthermore, RSV treatment upregulated CYP7A1
      expression and induced liver X receptor alpha (LXRalpha) activation in a time-
      and dose-dependent manner in HepG2 cells. In addition, the specific liver X
      receptor alpha (LXRalpha) inhibitor geranylgeranyl pyrophosphate (GGPP) inhibited
      the RSV-induced expression of CYP7A1 in HepG2 hepatocytes. CONCLUSION: The
      beneficial effects of RSV on HFD-induced hypercholesterolemia are mediated
      through LXRalpha signaling pathways, suggesting a potential target for the
      prevention of dyslipidemia.

PMID- 22607623
TI  - Population genetic structure of Ascaridia galli re-emerging in non-caged laying
      hens.
AB  - BACKGROUND: The poultry roundworm Ascaridia galli has reappeared in hens kept for
      egg production in Sweden after having been almost absent a decade ago. Today this
      is a frequent intestinal nematode parasite in non-caged laying hens. The aim of
      this study was to investigate the genetic diversity (Fst) in A. galli collected
      from different poultry production sites in southern Sweden, to identify possible
      common routes of colonization. METHODS: Adult parasites (n = 153) from 10 farms,
      including both broiler breeder parents and laying hens, were investigated by
      amplified restriction fragment length polymorphism analysis (AFLP). Worms from a
      Danish laying hen farm were also included for comparison. Most of the farms were
      represented by worms from a single host, but on two farms multiple samples from
      different hosts were assessed in order to study flock variation. RESULTS: A total
      of 97 fragments (loci) were amplified among which 81% were variable alleles. The
      average genetic diversity was 0.13 (range = 0.09-0.38), which is comparable to
      other AFLP studies on nematodes of human and veterinary importance. Within-farm
      variation showed that worms harboured by a single hen in a flock covered most of
      the A. galli genetic variation within the same flock (Fst = 0.01 and 0.03 for two
      farms). Between-farm analysis showed a moderate population genetic structure (Fst
      = 0.13), along with a low mutational rate but high gene flow between different
      farms, and absence of strong genetic selection. Network analysis showed repeated
      genetic patterns among the farms, with most worms on each farm clustering
      together as supported by high re-allocation rates. CONCLUSIONS: The investigated
      A. galli populations were not strongly differentiated, indicating that they have
      undergone a genetic bottlenecking and subsequent drift. This supports the view
      that the investigated farms have been recently colonized, and that new flocks are
      reinfected upon arrival with a stationary infection.

PMID- 22607624
TI  - Data mining identifies Digit Symbol Substitution Test score and serum cystatin C
      as dominant predictors of mortality in older men and women.
AB  - BACKGROUND: Characterization of long-term health trajectory in older individuals
      is important for proactive health management. However, the relative prognostic
      value of information contained in clinical profiles of nonfrail older adults is
      often unclear. METHODS: We screened 825 phenotypic and genetic measures evaluated
      during the Health, Aging, and Body Composition Study (Health ABC) baseline visit
      (3,067 men and women aged 70-79). Variables that best predicted mortality over 13
      years of follow-up were identified using 10-fold cross-validation. RESULTS:
      Mortality was most strongly associated with low Digit Symbol Substitution Test
      (DSST) score (DSST<25; 21.9% of cohort; hazard ratio [HR]=1.87+/-0.06) and
      elevated serum cystatin C (>=1.30 mg/mL; 12.1% of cohort; HR=2.25+/-0.07). These
      variables predicted mortality better than 823 other measures, including baseline
      age and a 45-variable health deficit index. Given elevated cystatin C (>=1.30
      mg/mL), mortality risk was further increased by high serum creatinine, high
      abdominal visceral fat density, and smoking history (2.52<=HR <=3.73). Given a
      low DSST score (<25) combined with low-to-moderate cystatin C (<1.30 mg/mL),
      mortality risk was highest among those with elevated plasma resistin and smoking
      history (1.90<=HR<=2.02). CONCLUSIONS: DSST score and serum cystatin C warrant
      priority consideration for the evaluation of mortality risk in older individuals.
      Both variables, taken individually, predict mortality better than chronological
      age or a health deficit index in well-functioning older adults (ages 70-79). DSST
      score and serum cystatin C can thus provide evidence-based tools for geriatric
      assessment.

PMID- 22607626
TI  - Multidimensional prognostic index and the estimated glomerular filtration rate.

PMID- 22607625
TI  - Leukocyte CCR2 expression is associated with mini-mental state examination score
      in older adults.
AB  - INTRODUCTION: Circulating inflammatory markers may play an important role in
      cognitive impairment at older ages. Mice deficient for the chemokine (C-C motif)
      receptor 2 (CCR2) develop an accelerated Alzheimer-like pathology. CCR2 is also
      important in neurogenesis. To identify human gene transcripts most closely
      associated with Mini-Mental State Examination (MMSE) scores, we undertook a
      genome-wide and inflammation specific transcriptome screen in circulating
      leukocytes from a population-based sample. METHODS: We measured in vivo
      transcript levels by microarray analysis in 691 subjects (mean age 72.6 years) in
      the InCHIANTI study (Invecchiare in Chianti, aging in the Chianti area). We
      assessed expression associations with MMSE performance at RNA collection and
      prior 9-year change in MMSE score in linear regression models. RESULTS: In genome
      wide analysis, raised CCR2 expression was cross-sectionally the most strongly
      associated transcript with lower MMSE score (beta=-0.16, p=5.1*10(-6), false
      discovery rate (FDR; q=0.077). Amongst inflammatory transcripts, only CCR2
      expression was associated with both MMSE score and accelerated decline in score
      over the preceding 9 years (beta=-0.16, p=5.1*10(-6), q=0.003; and beta=-0.13,
      p=5.5*10(-5), q=0.03, respectively). CCR2 expression was also positively
      associated with apolipoprotein E (ApoE) e4 Alzheimer disease risk haplotype.
      CONCLUSIONS: We show for the first time that CCR2 expression is associated with
      lower MMSE scores in an older human population. Laboratory models of Ccr2
      mediated beta-amyloid removal and regulation of neurogenesis affecting cognitive
      function may be applicable in humans. CCR2-mediated pathways may provide a
      possible focus for intervention to potentiate protective reactions to Alzheimer
      pathology in older people, including for people with an adverse ApoE haplotype.

PMID- 22607627
TI  - How genes influence life span: the biodemography of human survival.
AB  - BACKGROUND: In genome-wide association studies (GWAS) of human life span, none of
      the genetic variants has reached the level of genome-wide statistical
      significance. The roles of such variants in life span regulation remain unclear.
      DATA AND METHOD: A biodemographic analyses was done of genetic regulation of life
      span using data on low-significance longevity alleles selected in the earlier
      GWAS of the original Framingham cohort. RESULTS: Age-specific survival curves
      considered as functions of the number of longevity alleles exhibit regularities
      known in demography as "rectangularization" of survival curves. The presence of
      such pattern confirms observations from experimental studies that regulation of
      life span involves genes responsible for stress resistance. CONCLUSION:
      Biodemographic analyses could provide important information about the properties
      of genes affecting phenotypic traits.

PMID- 22607628
TI  - The conflict between DNA replication and transcription.
AB  - There is mounting evidence that there are frequent conflicts between complexes
      that replicate DNA and those that transcribe the same template, and that these
      conflicts lead to blockage of replication and genome instability. Such problems
      are perhaps best understood in bacteria, but it is becoming apparent that
      replicative barriers associated with transcription are a universal feature of
      life. This review summarizes what is currently known about how collisions between
      replisomes and transcription complexes are minimized and the mechanisms that help
      to resolve such collisions when they do occur. Although our understanding of
      these processes is still far from complete, a picture is emerging of a wide
      variety of different types of transcriptional blocks to replication that have
      resulted in a complex, overlapping system of mechanisms to avoid or tolerate such
      collisions.

PMID- 22607629
TI  - Anxiety, depression, and pain in burning mouth syndrome: first chicken or egg?
AB  - BACKGROUND: Burning mouth syndrome (BMS) is an idiopathic and chronic pain
      condition for which patients may experience high levels of pain, anxiety, and
      depression. So far, it has not yet been well investigated whether specific
      psychiatric features (anxious traits, personality disorder, or somatization) may
      play a role in the BMS pathogenesis or whether some BMS symptoms, or BMS itself,
      may cause secondary psychiatric symptoms. OBJECTIVE: The aim of this study was to
      evaluate the relationship between pain, depression, and anxiety in BMS and
      healthy patients in order to hypothesize a possible underlying pathogenetic
      model. METHODS: Fifty-three patients with BMS and 51 healthy volunteers matched
      for sex and age were enrolled. All patients underwent a physical examination,
      laboratory screening tests, and psychiatric assessment with the following
      instruments: Visual Analog Scale, the Hamilton Rating Scale for Depression, the
      State-Trait Anxiety Inventory Form Y 1-2 (STAI Y1-Y2), and the Symptom Checklist
      90-Revised (SCL-90-R). RESULTS: BMS patients and healthy volunteers showed a
      statistically significant difference in psychiatric features: Regression analysis
      showed that pain is affected by depression (R = 0.373; R(2) corrected = 0.123; F
      = 8.563; P < .005), and depression is affected by anxiety (R = 0.512; R(2)
      corrected = 0.248; F = 18.519; P < .001). BMS patients have statistically
      significant higher scores of anxiety (STAI Y1, P = .026 and STAI Y2, P = .046)
      and depression (P < .001), and higher SCL-90-R scores on somatization (P = .036)
      and hostility dimensions (P = .028) than the control group. CONCLUSIONS: We may
      hypothesize that anxiety could determine a secondary demoralization in BMS
      patients (depression) and depressive symptoms could contribute to pain,
      accordingly. Therefore, pain could be a somatic feature of depression. Our
      findings provide an example of a possible pathogenetic model for BMS.

PMID- 22607630
TI  - Theoretical study of negatively charged Fe(-)-(H2O)(n <= 6) clusters.
AB  - Interactions of a singly negatively charged iron atom with water molecules, Fe(-)
      (H(2)O)(n<=6), in the gas phase were studied by means of density functional
      theory. All-electron calculations were performed using the B3LYP functional and
      the 6-311++G(2d,2p) basis set for the Fe, O, and H atoms. In the lowest total
      energy states of Fe(-)-(H(2)O)(n), the metal-hydrogen bonding is stronger than
      the metal-oxygen one, producing low-symmetry structures because the water
      molecules are directly attached to the metal by basically one of their hydrogen
      atoms, whereas the other ones are involved in a network of hydrogen bonds, which
      together with the Fe(delta-)-H(delta+) bonding accounts for the nascent hydration
      of the Fe(-) anion. For Fe(-)-(H(2)O)(3<=n), three-, four-, five-, and six
      membered rings of water molecules are bonded to the metal, which is located at
      the surface of the cluster in such a way as to reduce the repulsion with the
      oxygen atoms. Nevertheless, internal isomers appear also, lying less than 3 or 5
      kcal/mol for n = 2-3 or n = 4-6. These results are in contrast with those of
      classical TM(+)-(H(2)O)(n) complexes, where the direct TM(+)-O bonding usually
      produces high symmetry structures with the metal defining the center of the
      complex. They show also that the Fe(-) anions, as the TM(+) ions, have great
      capability for the adsorption of water molecules, forming Fe(-)-(H(2)O)(n)
      structures stabilized by Fe(delta-)-H(delta+) and H-bond interactions.

PMID- 22607631
TI  - Emerging drugs for asthma.
AB  - INTRODUCTION: Current drug treatments for asthma relieve bronchospasm and airway
      inflammation but do not offer a cure, and symptoms return when treatment is
      stopped. Asthma management guidelines emphasize the importance of effective
      asthma treatment to achieve and maintain asthma control. However, despite widely
      available and effective treatments, achieving asthma control is still an unmet
      need for many patients. AREAS COVERED: Remarkable efforts have been made to
      identify the characteristic features of difficult-to-control (usually severe)
      asthma that are different from those described for mild-to-moderate asthma,
      setting the stage for the development of new and even individualized therapies.
      The most fascinating options of the new asthma treatments are biologic therapies,
      in particular monoclonal antibodies. In addition, some novel once-daily
      combinations of long-acting beta(2)-agonist and inhaled corticosteroids are under
      development. EXPERT OPINION: Asthma is a complex syndrome made up of a number of
      disease variants or asthma phenotypes, with different underlying pathophysiology.
      As different drugs target different pathways, it is necessary to determine the
      individual profile of pathophysiological abnormalities for each patient. Several
      cytokines have been implicated in the inflammatory cascades leading to the
      different asthma phenotypes, and the most relevant ones are discussed. The
      challenge in treating asthma resides precisely in its heterogeneity.

PMID- 22607632
TI  - Factors associated with low physical activity levels following pediatric cardiac
      transplantation.
AB  - BACKGROUND: Objectively measured MVPA levels following pediatric cardiac
      transplantation are unknown despite physical health implications. We sought to
      determine factors associated with MVPA in a pediatric cohort who had undergone
      cardiac transplantation. METHODS: Study assessments included maximal exercise
      testing (VO(2) max), accelerometry, and physical activity (HAES) and functional
      health status (CHQ-PF50) questionnaires. RESULTS: Participants (n = 20, 60% male,
      age: 11.8 +/- 3.0 yr old) had a VO(2) max of 28.5 +/- 6.8 mL/kg/min (%-predicted:
      65 +/- 14%) and maximal heart rate of 154 +/- 16 beats/min (%-predicted: 73 +/-
      7.5%). Participants performed a median of 7.6 min/day (Q1 4.0 min/day, Q3 11.0
      min/day) of MVPA. Each additional year of age at transplantation was associated
      with a decrease of 1.9 [1.0] min/day of MVPA (p = 0.07). Predicted VO(2) max,
      maximal power output, male sex, and age at study enrollment were not associated
      with an increase in MVPA. Parents' perception of their child's functional health
      status (CHQ-PF50) was lower on general health (p < 0.01) and family activity (p <
      0.01) domains relative to a population-based cohort of parents reporting on
      healthy children. CONCLUSION: Pediatric cardiac transplantation recipients may be
      indicated to participate in cardiac rehabilitation to optimize physical activity
      levels.

PMID- 22607634
TI  - Readiness to change as a moderator of outcome in transdiagnostic treatment.
AB  - Initial symptom severity is a client characteristic associated with psychotherapy
      outcome, although this relationship is not well-understood. Readiness to change
      is a factor that may influence this relationship. This study tested readiness as
      a moderator of the relationship between initial severity and symptom change. Data
      were derived from an RCT examining the efficacy of a transdiagnostic CBT
      treatment. Readiness was assessed with the URICA, and symptom and functioning
      outcomes were assessed. Multiple regression models indicated that severity was
      associated with less overall change, yet readiness moderated this relationship.
      At higher levels of readiness, the effect of initial severity on outcome was
      essentially reversed; for clients with higher initial readiness, higher levels of
      severity were associated with greater change.

PMID- 22607633
TI  - Demasculinization of the Anopheles gambiae X chromosome.
AB  - BACKGROUND: In a number of organisms sex-biased genes are non-randomly
      distributed between autosomes and the shared sex chromosome X (or Z). Studies on
      Anopheles gambiae have produced conflicting results regarding the
      underrepresentation of male-biased genes on the X chromosome and it is unclear to
      what extent sexual antagonism, dosage compensation or X-inactivation in the male
      germline, the evolutionary forces that have been suggested to affect the
      chromosomal distribution of sex-biased genes, are operational in Anopheles.
      RESULTS: We performed a meta-analysis of sex-biased gene expression in Anopheles
      gambiae which provides evidence for a general underrepresentation of male-biased
      genes on the X-chromosome that increased in significance with the observed degree
      of sex-bias. A phylogenomic comparison between Drosophila melanogaster, Aedes
      aegypti and Culex quinquefasciatus also indicates that the Anopheles X chromosome
      strongly disfavours the evolutionary conservation of male-biased expression and
      that novel male-biased genes are more likely to arise on autosomes. Finally, we
      demonstrate experimentally that transgenes situated on the Anopheles gambiae X
      chromosome are transcriptionally silenced in the male germline. CONCLUSION: The
      data presented here support the hypothesis that the observed demasculinization of
      the Anopheles X chromosome is driven by X-chromosome inactivation in the male
      germline and by sexual antagonism. The demasculinization appears to be the
      consequence of a loss of male-biased expression, rather than a failure in the
      establishment or the extinction of male-biased genes.

PMID- 22607635
TI  - Functional tooth units and nutritional status of older people in care homes in
      Indonesia.
AB  - OBJECTIVES: To investigate the relationship between functional tooth units (FTUs)
      and nutritional status. METHODS: One hundred females (mean age: 72.4 +/- 8.2
      years) at four private care homes in Jakarta, Indonesia were interviewed and
      clinically examined. The oral examination included the assessment of teeth,
      prosthetic status, and number of FTUs. The total number of FTUs was further
      divided by tooth composition: natural tooth against natural tooth (NN-FTUs),
      natural tooth against denture (ND-FTUs), and denture against denture (DD-FTUs).
      Nutritional status was evaluated using the body mass index (BMI) and the Mini
      Nutritional Assessment (MNA). RESULTS: The mean numbers of teeth present, NN
      FTUs, ND-FTUs, DD-FTUs, and total FTUs were 13.1 +/- 10.4, 1.7 +/- 3.0, 1.2 +/-
      3.3, 0.4 +/- 1.2 and 3.3 +/- 4.4, respectively. The mean BMI and MNA scores were
      24.8 +/- 5.0 and 22.6 +/- 2.8, respectively. Subjects with a normal BMI had a
      significantly higher total number of FTUs (3.6 +/- 4.6) compared with underweight
      subjects (0.1 +/- 0.3). Subjects with a normal MNA had a significantly higher
      number of NN-FTU (2.6 +/- 3.7) compared to those who were at risk or in a state
      of under-nutrition (1.2 +/- 2.4). CONCLUSION: This study revealed significant
      relationships between the number of FTUs and nutritional status. Keeping the
      posterior occlusion should be emphasized in order to maintain good nutritional
      status in older subjects.

PMID- 22607636
TI  - Human movement science.

PMID- 22607637
TI  - Directed metal (oxo) aliphatic C-H hydroxylations: overriding substrate bias.
AB  - The first general strategy for a directing effect on metal (oxo)-promoted C-H
      hydroxylations is described. Carboxylic acid moieties on the substrate overcome
      unfavorable electronic, steric, and stereoelectronic biases in C-H hydroxylations
      catalyzed by the non-heme iron complex Fe(PDP). In a demonstration of the power
      of this directing effect, C-H oxidation is diverted away from an electronically
      favored C-1 H abstraction/rearrangement pathway in the paclitaxel framework to
      enable installation of C-2 oxidation in the naturally occurring oxidation state
      and stereoconfiguration.

PMID- 22607639
TI  - Development of a novel PCR assay based on the 16S-23S rRNA internal transcribed
      spacer region for the detection of Lactococcus garvieae.
AB  - Lactococcus garvieae is recognized as an emerging pathogen in fish. Several PCR
      based methods have been developed for the detection and identification of L.
      garvieae; however, the sensitivity of these methods is still in question
      regarding the discrimination of this organism from other closely related species.
      Two primers, ITSLg30F and ITSLg319R, were designed from the sequence in the 16S
      23S internal transcribed spacer (ITS) region and used for the specific detection
      of L. garvieae. L. garvieae strains including fish isolates were positive by this
      method. In contrast, previously developed PCR methods showed false-positive
      results with non-L. garvieae species. Our results indicate that a PCR method
      using the newly designed ITS primer set provides a sensitive and efficient tool
      for the detection of L. garvieae in fish and aquaculture environments.

PMID- 22607638
TI  - Modeling rejection immunity.
AB  - BACKGROUND: Transplantation is often the only way to treat a number of diseases
      leading to organ failure. To overcome rejection towards the transplanted organ
      (graft), immunosuppression therapies are used, which have considerable side
      effects and expose patients to opportunistic infections. The development of a
      model to complement the physician's experience in specifying therapeutic regimens
      is therefore desirable. The present work proposes an Ordinary Differential
      Equations model accounting for immune cell proliferation in response to the
      sudden entry of graft antigens, through different activation mechanisms. The
      model considers the effect of a single immunosuppressive medication (e.g.
      cyclosporine), subject to first-order linear kinetics and acting by modifying, in
      a saturable concentration-dependent fashion, the proliferation coefficient. The
      latter has been determined experimentally. All other model parameter values have
      been set so as to reproduce reported state variable time-courses, and to maintain
      consistency with one another and with the experimentally derived proliferation
      coefficient. RESULTS: The proposed model substantially simplifies the chain of
      events potentially leading to organ rejection. It is however able to simulate
      quantitatively the time course of graft-related antigen and competent
      immunoreactive cell populations, showing the long-term alternative outcomes of
      rejection, tolerance or tolerance at a reduced functional tissue mass. In
      particular, the model shows that it may be difficult to attain tolerance at full
      tissue mass with acceptably low doses of a single immunosuppressant, in accord
      with clinical experience. CONCLUSIONS: The introduced model is mathematically
      consistent with known physiology and can reproduce variations in immune status
      and allograft survival after transplantation. The model can be adapted to
      represent different therapeutic schemes and may offer useful indications for the
      optimization of therapy protocols in the transplanted patient.

PMID- 22607640
TI  - Improving quality of care through improved audit and feedback.
AB  - BACKGROUND: The Department of Veterans Affairs (VA) has led the industry in
      measuring facility performance as a critical element in improving quality of
      care, investing substantial resources to develop and maintain valid and cost
      effective measures. The External Peer Review Program (EPRP) of the VA is the
      official data source for monitoring facility performance, used to prioritize the
      quality areas needing most attention. Facility performance measurement has
      significantly improved preventive and chronic care, as well as overall quality;
      however, much variability still exists in levels of performance across measures
      and facilities. Audit and feedback (A&F), an important component of effective
      performance measurement, can help reduce this variability and improve overall
      performance. Previous research suggests that VA Medical Centers (VAMCs) with high
      EPRP performance scores tend to use EPRP data as a feedback source. However, the
      manner in which EPRP data are used as a feedback source by individual providers
      as well as service line, facility, and network leadership is not well understood.
      An in-depth understanding of mental models, strategies, and specific feedback
      process characteristics adopted by high-performing facilities is thus urgently
      needed.This research compares how leaders of high, low, and moderately performing
      VAMCs use clinical performance data from the EPRP as a feedback tool to maintain
      and improve quality of care. METHODS: We will conduct a qualitative, grounded
      theory analysis of up to 64 interviews using a novel method of sampling primary
      care, facility, and Veterans Integrated Service Network (VISN) leadership at high
      , moderate-, and low-performing facilities. We will analyze interviews for
      evidence of cross-facility differences in perceptions of performance data
      usefulness and strategies for disseminating performance data evaluating
      performance, with particular attention to timeliness, individualization, and
      punitiveness of feedback delivery. DISCUSSION: Most research examining feedback
      to improve provider and facility performance lacks a detailed understanding of
      the elements of effective feedback. This research will highlight the elements
      most commonly used at high-performing facilities and identify additional features
      of their successful feedback strategies not previously identified. Armed with
      this information, practices can implement more effective A&F interventions to
      improve quality of care.

PMID- 22607641
TI  - Tuning to water sustainability: future opportunity for China.

PMID- 22607642
TI  - Combining intermediate levels of the Endotoxin Activity Assay (EAA) with other
      biomarkers in the assessment of patients with sepsis: results of an observational
      study.
AB  - INTRODUCTION: The Endotoxin Activity Assay (EAA) is a useful test to risk
      stratify patients with severe sepsis and assess for Gram negative infection.
      However, the significance of intermediate levels of EAA (0.4-0.59) at the bedside
      has not been well elucidated. The purpose of this study was to interpret
      intermediate EAA levels in clinical practice. METHODS: This retrospective
      observational study included all adult patients with suspected sepsis admitted to
      our medico-surgical intensive care unit (ICU) in whom EAA was measured from July
      2008 to September 2011. Data collected included EAA, white blood cell (WBC) count
      and differential, C-reactive protein (CRP), procalcitonin (PCT) and bacterial
      cultures. Data were analyzed by comparative statistics. RESULTS: Two hundred and
      ten patients were studied. Ninety two (43%) patients had culture documented gram
      negative infection. Patients with Gram-negative organisms in cultures had
      significantly higher EAA levels (0.47, IQR 0.27) than those without any Gram
      negative organisms in cultures (0.34, IQR 0.22) (p < 0.0001). For patients with
      intermediate EAA levels (0.40 to 0.59), PCT levels and presence of left shift of
      WBC significantly differed between patients with Gram negative organisms in their
      blood or other cultures and those who had no organisms in any of the cultures
      (4.9 versus 1.7 ng/mL, p < 0.05; 57.9 versus 18.9%, p < 0.0004, respectively).
      CONCLUSIONS: We confirm that high levels of EAA in our cohort of patients with
      suspected sepsis are strongly associated with gram negative infection. In those
      patients with intermediate elevation in EAA levels, use of PCT and WBC
      differential can provide additional diagnostic value to clinicians at the
      bedside.

PMID- 22607643
TI  - Vitamin D intake and cardiovascular mortality in the NHANES I epidemiological
      follow-up study cohort.
AB  - The objective of the present study was to determine whether vitamin D intake is
      associated with CVD mortality in a general population sample. The association
      between vitamin D intake and CVD mortality (ICD-9 code 410-414) rates was
      investigated using data from the the First National Health and Nutrition
      Examination Survey (NHANES I) Epidemiological Follow-up Study (NHEFS) 1971-1992.
      Overall, higher vitamin D intake was associated with lower CVD mortality. After
      adjustment for traditional risk factors for CVD, vitamin D intake showed mild but
      nonstatistically significant protective effects against CVD mortality with a
      hazard ratio for adequate as compared to low intake (with 95% confidence
      intervals) of 0.90 (0.74, 1.08). Hazard ratios were 0.95, 0.83, 0.88, and 1.02,
      in males, females, Whites, and Blacks, respectively (with 95% confidence
      intervals overlapping 1.0 in all cases). Thus, we did not find a statistically
      significant association between vitamin D intake and CVD mortality, although our
      findings are compatible with a mild protective effect, especially among females
      and Whites.

PMID- 22607644
TI  - Probable etoposide interaction with Echinacea.
AB  - Echinacea is an herbal supplement commonly used as an immune system stimulant to
      prevent infections, such as the common cold or flu. Echinacea has been documented
      as a cyctochrome P450 (CYP) 3A4 inhibitor in vitro, but no formal studies have
      been conducted in humans. Etoposide is a cytotoxic, topoisomerase II inhibitor,
      chemotherapeutic agent used in the treatment of lung cancer. Etoposide is
      primarily metabolized by CYP 3A4. We report the first possible drug-herbal
      interaction between Echinacea and etoposide. A 61-year-old gentleman newly
      diagnosed with nonsmall cell lung cancer began concurrent chemoradiation with
      cisplatin and etoposide. He was admitted to the hospital on day 8 of his first
      cycle and found to be thrombocytopenic. His platelet count eventually reached a
      nadir of 16 * 10(3)/L, requiring platelet transfusion support. Upon admission, it
      was discovered he was taking Echinacea, which was discontinued. He received his
      next cycle of chemotherapy without taking Echinacea. His platelet count decreased
      to a nadir of 44 * 10(3)/L, but he did not require platelet transfusions.
      Echinacea likely contributed to this patient's profound thrombocytopenia and
      should be avoided in patients receiving etoposide and possibly other
      chemotherapeutic drugs that are CYP 3A4 substrates.

PMID- 22607645
TI  - Mechanisms of action of phenolic compounds in olive.
AB  - Olive oil, an oil rich in monounsaturated fatty acids (MUFCs) and minor
      constituents including phenolic compounds, is a major component of the
      Mediterranean diet. The potential health benefits of the Mediterranean diet were
      highlighted by the seminal Seven Countries Study, and more contemporary research
      has identified olive oil as a major element responsible for these effects. It is
      emerging that the phenolic compounds are the most likely candidates accounting
      for the cardioprotective and cancer preventative effects of extra virgin olive
      oil (EVOO). In particular, the phenolic compound, hydroxytyrosol has been
      identified as one of the most potent antioxidants found in olive oil. This review
      will briefly consider historical aspects of olive oil research and the biological
      properties of phenolic compounds in olive oil will be discussed. The focus of the
      discussion will be related to the mechanisms of action of hydroxytyrosol. Studies
      have demonstrated that hydroxytyrosol induces apoptosis and cell cycle arrest in
      cancer cells. Further, research has shown that hydroxytyrosol can prevent
      cardiovascular disease by reducing the expression of adhesion molecules on
      endothelial cells and preventing the oxidation of low-density lipoprotein (LDL).
      The molecular mechanisms accounting for these effects are reviewed.

PMID- 22607646
TI  - Evidence for using alpha-lipoic acid in reducing lipoprotein and inflammatory
      related atherosclerotic risk.
AB  - Alpha lipoic acid (alpha-LA) is a potent biological antioxidant that is found
      naturally in the human body at very low concentrations, primarily in the
      mitochondria. However, synthetic alpha-LA is commercially available as a
      nutritional supplement and has been shown to be effective at ameliorating
      symptoms in diseases with an underlying oxidative stress component. High blood
      cholesterol is a major cardiovascular disease (CVD) risk factor and is responsive
      to diet and lifestyle modifications. In addition to high blood cholesterol, there
      is increasing evidence that supports the independent role of oxidized lipids and
      lipoproteins, chiefly oxidized low-density lipoproteins (Ox-LDL), in the
      development of CVD. Lowering total blood cholesterol (TC), LDL cholesterol (LDL
      C), and triglycerides (TG) and raising high-density lipoprotein cholesterol (HDL
      C) levels is the most desirable metabolic state for maximum protection against
      CVD, but can be difficult to achieve through diet and exercise alone. With
      emerging evidence of reduced LDL-C and TG, increased HDL-C, and blunting of
      oxidative susceptibility of lipoproteins by alpha-LA, its use alone or in
      combination with other dietary supplements may be an effective strategy to
      modulate multiple metabolic targets of oxidative stress and cholesterol
      metabolism to reduce CVD risk. This review examines the current evidence for the
      use of alpha-LA in CVD risk reduction and identifies the remaining gaps that must
      be addressed in this area of research.

PMID- 22607648
TI  - Utility of Nociceptive Flexion Reflex Threshold, Bispectral Index, Composite
      Variability Index and Noxious Stimulation Response Index as measures for
      nociception during general anaesthesia.
AB  - Movement and haemodynamic responses to noxious stimuli during general anaesthesia
      are regarded as signs of nociception. We compared the Nociceptive Flexion Reflex
      Threshold (NFRT), Bispectral Index (BIS), Composite Variability Index (CVI),
      Noxious Stimulation Response Index (NSRI) and the calculated
      propofol/remifentanil effect-compartment concentrations (Ce) as predictors for
      such responses in 50 female subjects at laryngeal mask airway insertion and skin
      incision. The following prediction probabilities (PK-values) were obtained at
      laryngeal mask airway insertion and skin incision, respectively. For movement
      responses: NFRT = 0.77 and 0.72; p = 0.0001 and 0.004, respectively; BIS = 0.41
      and 0.56, p = 0.29 and 0.5, respectively; CVI = 0.48 and 0.57, p = 0.76 and 0.88,
      respectively; NSRI = 0.49 and 0.76, p = 0.92 and 0.0001, respectively; propofol
      Ce = 0.35 and 0.66, p = 0.04 and 0.03, respectively; remifentanil-Ce = 0.68 and
      0.72, p = 0.01 and 0.003, respectively. For heart rate responses: NFRT = 0.68 and
      0.75, p = 0.04 and 0.01, respectively; BIS = 0.37 and 0.59, p = 0.15 and 0.41,
      respectively; CVI = 0.41 and 0.44, p = 0.39 and 0.37, respectively; NSRI = 0.48
      and 0.53, p = 0.84 and 0.78, respectively; propofol-Ce = 0.42 and 0.56, p = 0.39
      and 0.53, respectively; remifentanil-Ce = 0.58 and 0.54, p = 0.35 and 0.73,
      respectively. We conclude that the NFRT best predicts movement and heart rate
      responses to noxious stimuli. Effect-compartment concentrations and NSRI also
      predict movement (but not heart rate) responses satisfactorily.

PMID- 22607647
TI  - An evidence-based systematic review of acai (Euterpe oleracea) by the Natural
      Standard Research Collaboration.
AB  - An evidence-based systematic review of acai (Euterpe oleracea) by the Natural
      Standard Research Collaboration consolidates the safety and efficacy data
      available in the scientific literature using a validated, reproducible grading
      rationale. This article includes written and statistical analysis of clinical
      trials, plus a compilation of expert opinion, folkloric precedent, history,
      pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and
      dosing.

PMID- 22607649
TI  - Chondrogenesis by co-culture of adipose-derived stromal cells and chondrocytes in
      vitro.
AB  - Adipose-derived stromal cells (ADSCs) could be induced to differentiate into
      chondrocytes in the presence of cellular factors. In this study, we explored the
      feasibility of inducing the differentiation of ADSCs into chondrocytes in the
      presence of chondrocytes. Human ADSCs and porcine auricular chondrocytes were
      expanded in vitro and then were mixed at the ratio of 7:3. 5.0 * 10(7) mixed
      cells were seeded onto a polyglycolic acid/polylactic acid scaffold as co-culture
      group. Chondrocytes and ADSCs with the same cell number were seeded onto the
      scaffold as positive control group and negative control group. A total of 1.5 *
      10(7) chondrocytes were seeded as low-concentration chondrocyte group. After
      culturing for 8 weeks, gross observation, wet weight, histology,
      glycosaminoglycan quantification, and collagen II expression were evaluated.
      Cells in all groups well adhered to the scaffold and could secrete extracellular
      matrices. In the co-culture group and positive control group, cell-scaffold
      constructs could maintain the original size and shape during the culture. At the
      8th week, cartilage-like tissues were formed, and abundant type II collagen could
      be detected by immunohistochemistry and reverse transcription-polymerase chain
      reaction in co-culture and positive control groups. Wet weights and
      glycosaminoglycan contents of tissues in co-culture group were approximately
      onefold of those in the negative control group. In the negative control group,
      constructs shrunk gradually without mature cartilage lacuna formation. In low
      concentration chondrocyte group, constructs also shrunk obviously with small
      amount of cartilage formation. Chondrocytes can provide chondrogenic
      microenvironment to induce chondrogenic differentiation of ADSCs and thus promote
      the chondrogenesis of ADSCs in vitro.

PMID- 22607650
TI  - Relationships between family physicians' referral for palliative radiotherapy,
      knowledge of indications for radiotherapy, and prior training: a survey of rural
      and urban family physicians.
AB  - BACKGROUND: The primary objective of this research was to assess the relationship
      between FPs' knowledge of palliative radiotherapy (RT) and referral for
      palliative RT. METHODS: 1001 surveys were sent to FPs who work in urban,
      suburban, and rural practices. Respondents were tested on their knowledge of
      palliative radiotherapy effectiveness and asked to report their self-assessed
      knowledge. RESULTS: The response rate was 33%. FPs mean score testing their
      knowledge of palliative radiotherapy effectiveness was 68% (SD = 26%). The
      majority of FPs correctly identified that painful bone metastases (91%), airway
      obstruction (77%), painful local disease (85%), brain metastases (76%) and spinal
      cord compression (79%) can be effectively treated with RT, though few were aware
      that hemoptysis (42%) and hematuria (31%) can be effectively treated. There was a
      linear relationship between increasing involvement in palliative care and both
      self-assessed (p < 0.001) and tested (p = 0.02) knowledge. FPs had higher mean
      knowledge scores if they received post-MD training in palliative care (12%
      higher; p < 0.001) or radiotherapy (15% higher; p = 0.002). There was a strong
      relationship between FPs referral for palliative radiotherapy and both self
      assessed knowledge (p < 0.001) and tested knowledge (p = 0.01). CONCLUSIONS: Self
      assessed and tested knowledge of palliative RT is positively associated with
      referral for palliative RT. Since palliative RT is underutilized, further
      research is needed to assess whether family physician educational interventions
      improve palliative RT referrals. The current study suggests that studies could
      target family physicians already in practice, with educational interventions
      focusing on hemostatic and other less commonly known indications for palliative
      RT.

PMID- 22607651
TI  - Prevalence of Rift Valley Fever among ruminants, Mayotte.
AB  - Rift Valley fever threatens human and animal health. After a human case was
      confirmed in Comoros in 2007, 4 serosurveys among ruminants in Mayotte suggested
      that Rift Valley fever virus had been circulating at low levels since 2004,
      although no clinical cases occurred in animals. Entomologic and ecologic studies
      will help determine outbreak potential.

PMID- 22607652
TI  - Novel variant of Beilong Paramyxovirus in rats, China.

PMID- 22607654
TI  - Relationship between markers of inflammation and anaemia in children of Papua New
      Guinea.
AB  - OBJECTIVE: To assess the association of the acute-phase protein biomarkers, C
      reactive protein (CRP) and alpha1-acid glycoprotein (AGP), with anaemia in
      children aged 6-59.9 months in Papua New Guinea. DESIGN: A nationally
      representative household-based cross-sectional survey of children aged 6-59.9
      months was used to assess the relationships between various combinations of
      elevated CRP (>5 mg/l) and AGP (>1.2 g/l) with anaemia. Logistic regression was
      used to determine if other factors, such as age, sex, measures of anthropometry,
      region, urban/rural residence and household size, modified or confounded the
      acute-phase protein-anaemia association. SETTING: Papua New Guinea. SUBJECTS: A
      total of 870 children aged 6-59.9 months from the 2005 Papua New Guinea National
      Micronutrient Survey were assessed. RESULTS: The following prevalence estimates
      were found: anaemia 48 %; elevated CRP 32 %; and elevated AGP 33 %. Children with
      elevated CRP had a prevalence of anaemia of 66 % compared with children with
      normal CRP who had a prevalence of 40 %. Corresponding estimates for AGP were 61
      % and 42 %, respectively. Similar results were found with combinations of
      elevated CRP and AGP. The higher prevalence of anaemia in children with elevated
      CRP and/or AGP was still present after controlling for confounders. CONCLUSIONS:
      Elevated levels of CRP and AGP were significantly associated with a higher
      prevalence of anaemia in the children surveyed. There are no expert group
      recommendations on whether to or how to account for markers of inflammation in
      presenting results on anaemia prevalence. Additional research would be helpful to
      clarify this issue.

PMID- 22607653
TI  - The aged microenvironment contributes to the age-related functional defects of
      CD4 T cells in mice.
AB  - CD4 T cells, and especially T follicular helper cells, are critical for the
      generation of a robust humoral response to an infection or vaccination.
      Importantly, immunosenescence affects CD4 T-cell function, and the accumulation
      of intrinsic defects decreases the cognate helper functions of these cells.
      However, much less is known about the contribution of the aged microenvironment
      to this impaired CD4 T-cell response. In this study, we have employed a
      preclinical model to determine whether the aged environment contributes to the
      defects in CD4 T-cell functions with aging. Using an adoptive transfer model in
      mice, we demonstrate for the first time that the aged microenvironment negatively
      impacts at least three steps of the CD4 T-cell response to antigenic stimulation.
      First, the recruitment of CD4 T cells to the spleen is reduced in aged compared
      to young hosts, which correlates with dysregulated chemokine expression in the
      aged organ. Second, the priming of CD4 T cells by DCs is reduced in aged compared
      to young mice. Finally, naive CD4 T cells show a reduced transition to a T
      follicular helper cell phenotype in the aged environment, which impairs the
      subsequent generation of germinal centers. These studies have provided new
      insights into how aging impacts the immune system and how these changes influence
      the development of immunity to infections or vaccinations.

PMID- 22607656
TI  - Excess electron interactions with solvated DNA nucleotides: strand breaks
      possible at room temperature.
AB  - When biological matter is subjected to ionizing radiation, a wealth of secondary
      low-energy (<20 eV) electrons are produced. These electrons propagate
      inelastically, losing energy to the medium until they reach energies low enough
      to localize in regions of high electron affinity. We have recently shown that in
      fully solvated DNA fragments, nucleobases are particularly attractive for such
      excess electrons. The next question is what is their longer-term effect on DNA.
      It has been advocated that they can lead to strand breaks by cleavage of the
      phosphodiester C(3')-O(3') bond. Here we present a first-principles study of free
      energy barriers for the cleavage of this bond in fully solvated nucleotides. We
      have found that except for dAMP, the barriers are on the order of 6 kcal/mol,
      suggesting that bond cleavage is a regular feature at 300 K. Such low barriers
      are possible only as a result of solvent and thermal fluctuations. These findings
      support the notion that low-energy electrons can indeed lead to strand breaks in
      DNA.

PMID- 22607655
TI  - Robust spinal neuroinflammation mediates mechanical allodynia in Walker 256
      induced bone cancer rats.
AB  - It has been reported that remarkable and sustained activation of astrocytes
      and/or microglia occurs in cancer induced pain (CIP), which is different from
      neuropathic and inflammatory pain. The present study was designed to investigate
      the role of spinal Toll-like receptor 4 (TLR4) induced glial neuroinflammation in
      cancer induced pain using a modified rat model of bone cancer. The rat model of
      CIP consisted of unilateral intra-tibial injection with Walker 256 mammary gland
      carcinoma. Nine days after Walker 256 inoculation, a robust activation of both
      astrocytes and microglia in bilateral spinal dorsal horn was observed together
      with significant bilateral mechanical allodynia. This neuroinflammation was
      characterized by enhanced immunostaining of both glial fibrillary acidic protein
      (GFAP, astrocyte marker) and OX-42 (microglia marker), and an elevated level of
      IL-1beta, IL-6 and TNF-alpha mRNA. I.t. administration of fluorocitrate (an
      inhibitor of glial metabolism, 1 nmol) or minocycline (an inhibitor of microglia,
      100 MUg) has significant anti-allodynic effects on day 12 after Walker 256
      inoculation. Naloxone (a nonstereoselective TLR4 signaling blocker, 60 MUg, i.t.)
      also significantly alleviated mechanical allodynia and simultaneously blocked the
      increased inflammatory cytokine mRNA. The results suggested that spinal TLR4
      might play an important role in the sustained glial activation that critically
      contributed to the robust and sustained spinal neuroinflammation in CIP. This
      result could potentially help clinicians and researchers to better understand the
      mechanism of complicated cancer pain.

PMID- 22607657
TI  - Wnt-4 potently inhibits capillary outgrowth from rat aorta in 3D culture.
AB  - Regulation of angiogenesis involves tight cell-to-cell and cell-to-extracellular
      matrix interactions. Various reports demonstrate that the Wnt signaling pathways
      participate in this regulation. Using a three-dimensional aortic ring culture
      combined with an ex vivo retroviral infection approach, we evaluated the effects
      of two Wnt growth factors, Wnt-1 and Wnt-4, on the formation and growth of new
      capillaries. Our results show that Wnt-1 had no effect, whereas Wnt-4 was a
      potent inhibitor of capillary outgrowth in vitro.

PMID- 22607659
TI  - Chondroid lipoma: an update and review.
AB  - Chondroid lipoma is a rare, benign soft tissue tumor with features of both
      embryonal fat and embryonal cartilage that most often arises in the proximal limb
      and limb girdles of adult women. Histologically, it comprises nests and cords of
      rounded cells with granular eosinophilic or multivacuolated, lipid-containing
      cytoplasm within prominent myxohyaline stroma and may be morphologically confused
      with some sarcomas. Correct diagnosis is crucial to avoid overtreatment because
      it does not recur or metastasize, and simple excision is curative. The etiology
      of chondroid lipoma remains unknown, but it appears genetically distinct, with a
      reciprocal t(11;16)(q13;p13) translocation identified in an increasing number of
      cases. We review the literature on chondroid lipoma, discussing tumor histology,
      immunohistochemistry, ultrastructure, and differential diagnosis, and summarize
      the molecular genetic features so far known.

PMID- 22607658
TI  - Oral contraception and energy intake in women: impact on substrate oxidation
      during exercise.
AB  - Oral contraception (OC) and energy intake may play a role in fuel selection
      during exercise. The aim of this study was to investigate the effect of OCs (OC+
      vs. OC-) in fed and fasting conditions on substrate oxidation and metabolic and
      hormonal responses in women during exercise. Substrate oxidation (respiratory
      exchange ratio and lipid and carbohydrates oxidation rates), metabolic (glycerol,
      free fatty acids (FFA), and glucose), and hormonal (insulin, adrenaline, and
      noradrenaline) responses were determined in 21 women: 10 regularly menstruating
      women (OC-) and 11 women using OCs (OC+: low-dose monophasic pill; ethinyl
      estradiol <= 30 ug) during 45 min at 65% of maximal oxygen consumption in fasting
      and postprandial states. At rest, OC+ presented higher low-density lipoprotein
      cholesterol, total cholesterol, and triglyceride plasma concentrations as
      compared with OC-. OC status had no influence on substrate oxidation and
      metabolic and hormonal responses during exercise. In the fasting state, whatever
      the OC status, women exhibited greater reliance on fat than in postprandial
      condition. This occurred in the presence of lower plasma insulin concentrations
      and higher plasma FFA and glycerol levels. The results indicated that the use of
      low-dose monophasic combined with OCs did not modify fuel selection and metabolic
      and hormonal responses during exercise in women. The fasting condition, compared
      with the fed condition, decreased carbohydrate oxidation during exercise, leading
      to a greater lipid mobilization and utilization whatever the OC status. Thus, in
      women, the realization of an exercise in either the fed or fasting conditions had
      a greater impact on substrate oxidation than OC status.

PMID- 22607660
TI  - Too far, too long, too few: workforce planning in dermatology.

PMID- 22607661
TI  - Occupational exposures to hand-arm vibration, whole-body vibration, and noise
      among crane operators in construction: a pilot study.

PMID- 22607662
TI  - Alignment effect of N2(A3Sigmau+) in the energy transfer reaction of aligned
      N2(A3Sigmau+) + NO(X2Pi) -> NO(A2Sigma+) + N2(X1Sigmag+).
AB  - Steric effect in the energy transfer reaction of N(2)(A(3)Sigma(u)(+)) +
      NO(X(2)Pi) -> NO(A(2)Sigma(+)) + N(2)(X(1)Sigma(g)(+)) has been studied under
      crossed beam conditions at a collision energy of ~0.07 eV by using an aligned
      N(2)(A(3)Sigma(u)(+)) beam prepared by a magnetic hexapole. The emission
      intensity of NO(A(2)Sigma(+)) has been measured as a function of the magnetic
      orientation field direction (i.e., alignment of N(2)(A(3)Sigma(u)(+))) in the
      collision frame. A significant alignment effect on the energy transfer
      probability is observed. The shape of the steric opacity function turns out to be
      most reactive at the oblique configuration of N(2)(A(3)Sigma(u)(+)) with an
      orientation angle of gamma(v(R)) ~ 45 degrees  with respect to the relative
      velocity vector (v(R)), which has a good correlation with the spatial
      distribution of the 2ppi(g)* molecular orbital of N(2)(A(3)Sigma(u)(+)). We
      propose the electron exchange mechanism in which the energy transfer probability
      is dominantly controlled by the orbital overlap between N(2)(2ppi(g)*) and
      NO(6sigma).

PMID- 22607664
TI  - Efficiency of donor cell preparation and recipient oocyte source for production
      of transgenic cloned dairy goats harboring human lactoferrin.
AB  - The objective was to investigate the effects of the transgenic donor cell
      synchronization method, oocyte sources, and other factors, on production of hLF
      gene nucleus transfer dairy goats. Three transfected cell lines from ear biopsies
      from three 3-mo-old Saanen dairy goats (designated Number 1, Number 2, and Number
      3, respectively) were selected as karyoplast donors for somatic cell nuclear
      transfer (SCNT) after detailed identification (including PCR and sequencing of
      PCR products). In donor cell cycle synchronization studies, the apoptosis rate of
      hLF transgenic fibroblasts was not different (P > 0.05) after 3 days of serum
      starvation or 2 days of contact inhibition. Additionally, there was no effect (P
      > 0.05) on developmental capacity of reconstructed embryos; however, the kidding
      rate of recipients in the serum starvation group was higher than that in the
      contact inhibition group (18 vs. 0%, respectively). The production efficiency of
      the transgenic cloned goats using donor cells from the Number 1 dairy goat cell
      line was higher than those using the Number 2 and the Number 3 cell lines
      (kidding rates were 18, 2, and 0%, respectively, P < 0.05). The oocyte source did
      not significantly affect the pregnancy rate of hLF-transgenic cloned dairy goats,
      but more fetuses were aborted when using in vitro matured oocytes compared to in
      vivo matured oocytes. In summary, utilizing transfected 3-mo-old dairy goat
      fibroblasts as donor cells, seven live offspring were produced, and the hLF gene
      was successfully integrated. This study provided additional insights into
      preparation of donor cells and recipient oocytes for producing transgenic cloned
      goats through SCNT.

PMID- 22607663
TI  - Nurses' research utilization two years after graduation--a national survey of
      associated individual, organizational, and educational factors.
AB  - BACKGROUND: Nurses' research utilization (RU) as part of evidence-based practice
      is strongly emphasized in today's nursing education and clinical practice. The
      primary aim of RU is to provide high-quality nursing care to patients. Data on
      newly graduated nurses' RU are scarce, but a predominance of low use has been
      reported in recent studies. Factors associated with nurses' RU have previously
      been identified among individual and organizational/contextual factors, but there
      is a lack of knowledge about how these factors, including educational ones,
      interact with each other and with RU, particularly in nurses during the first
      years after graduation. The purpose of this study was therefore to identify
      factors that predict the probability for low RU among registered nurses two years
      after graduation. METHODS: Data were collected as part of the LANE study
      (Longitudinal Analysis of Nursing Education), a Swedish national survey of
      nursing students and registered nurses. Data on nurses' instrumental, conceptual,
      and persuasive RU were collected two years after graduation (2007, n = 845),
      together with data on work contextual factors. Data on individual and educational
      factors were collected in the first year (2002) and last term of education
      (2004). Guided by an analytic schedule, bivariate analyses, followed by logistic
      regression modeling, were applied. RESULTS: Of the variables associated with RU
      in the bivariate analyses, six were found to be significantly related to low RU
      in the final logistic regression model: work in the psychiatric setting, role
      ambiguity, sufficient staffing, low work challenge, being male, and low student
      activity. CONCLUSIONS: A number of factors associated with nurses' low extent of
      RU two years postgraduation were found, most of them potentially modifiable.
      These findings illustrate the multitude of factors related to low RU extent and
      take their interrelationships into account. This knowledge might serve as useful
      input in planning future studies aiming to improve nurses', specifically newly
      graduated nurses', RU.

PMID- 22607665
TI  - Geriatric gynecology: promoting health and avoiding harm.
AB  - Age increases vulnerability, commonly accompanied by greater reliance on others
      and susceptibility to maltreatment. Physiologic processes become less resilient;
      the potential for harm from medical care increases. Awareness of frailty,
      functional, social, and potential maltreatment issues enables early referrals to
      help the patient maintain her independence. Health issues that may impede both
      gynecologic care and self-sufficiency include sensory deficits, physical
      disability, and cognitive impairment. Speaking slowly and providing contextual
      information enhance patient comprehension. Cancer screening depends on life
      expectancy. Osteoporosis treatment requires managing fall risk. Gynecologic
      symptoms more likely have multiple contributing factors than one etiology.
      Incontinence is a particularly complex issue, but invariably includes bladder
      diary assessment and pelvic floor muscle training. Function and frailty measures
      best predict perioperative morbidity. Communication with the patient, her family,
      other providers, and health care organizations is an important frontier in
      avoiding errors and adverse outcomes.

PMID- 22607666
TI  - Smoking during pregnancy influences the maternal immune response in mice and
      humans.
AB  - OBJECTIVE: During pregnancy the maternal immune system has to adapt its response
      to accommodate the fetus. The objective of this study was to analyze the effects
      of smoking on the maternal immune system. STUDY DESIGN: First-trimester decidual
      tissue and peripheral blood of smoking and nonsmoking women were analyzed by real
      time reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry.
      A mouse model was used to further analyze the effects of smoking. Murine tissue
      was analyzed by flow cytometry, real-time RT-PCR, and immunohistochemistry.
      RESULTS: Smoking caused lower percentages of viable pups in mice and lower
      birthweights in humans. Smoking mothers, both mice and human, had more natural
      killer cells and inflammatory macrophages locally, whereas systemically they had
      lower percentages of regulatory T cells than nonsmoking controls. CONCLUSION:
      Maternal smoke exposure during pregnancy influences local and systemic immune
      responses in both women and mice. Such changes may be involved in adverse
      pregnancy outcomes in smoking individuals.

PMID- 22607667
TI  - The diagnosis, treatment, and follow-up of cesarean scar pregnancy.
AB  - OBJECTIVE: The diagnosis and treatment of cesarean scar pregnancy (CSP) is
      challenging. The objective of this study was to evaluate the diagnostic method,
      treatments, and long-term follow-up of CSP. STUDY DESIGN: This is a retrospective
      case series of 26 patients between 6-14 postmenstrual weeks suspected to have CSP
      who were referred for diagnosis and treatment. The diagnosis was confirmed with
      transvaginal ultrasound. In 19 of the 26 patients the gestational sac was
      injected with 50 mg of methotrexate: 25 mg into the area of the embryo/fetus and
      25 mg into the placental area; and an additional 25 mg was administered
      intramuscularly. Serial serum human chorionic gonadotropin determinations were
      obtained. Gestational sac volumes and vascularization were assessed by 3
      dimensional ultrasound and used to monitor resolution of the injected site and
      outcome. RESULTS: The 19 treated pregnancies were followed for 24-177 days. No
      complications were observed. After the treatment, typically, there was an initial
      increase in the human chorionic gonadotropin serum concentrations as well as in
      the volume of the gestational sac and their vascularization. After a variable
      time period mentioned elsewhere the values decreased, as expected. CONCLUSION:
      Combined intramuscular and intragestational methotrexate injection treatment was
      successful in treating these CSP.

PMID- 22607668
TI  - N-Methyl-3-(tetrahydro-2H-pyran-4-yl)-2,3,4,9-tetrahydro-1H-carbazole-6
      carboxamides as a novel class of cannabinoid receptors agonists with low CNS
      penetration.
AB  - Cannabinoid CB(1) receptor agonists exhibit potent analgesic effects in rodents
      and humans, but their clinical utility as analgesic drugs is often limited by
      centrally mediated side effects. We report herein the preparation of N-methyl-3
      (tetrahydro-2H-pyran-4-yl)-2,3,4,9-tetrahydro-1H-carbazole-6-carboxamides as a
      novel class of hCB(1)/hCB(2) dual agonists with attractive physicochemical
      properties. More specifically, (R)-N,9-dimethyl-N-(4-(methylamino)-4-oxobutyl)-3
      (tetrahydro-2H-pyran-4-yl)-2,3,4,9-tetrahydro-1H-carbazole-6-carboxamide,
      displayed an extremely low level of CNS penetration (Rat Cbr/Cplasma=0.005 or
      0.5%) and was devoid of CNS side effects during pharmaco-dynamic testing.

PMID- 22607669
TI  - Structure-based design of 2,6,7-trisubstituted-7H-pyrrolo[2,3-d]pyrimidines as
      Aurora kinases inhibitors.
AB  - This Letter reports the optimization of a pyrrolopyrimidine series as dual
      inhibitors of Aurora A/B kinases. This series derived from a pyrazolopyrimidine
      series previously reported as inhibitors of aurora kinases and CDKs. In an effort
      to improve the selectivity of this chemotype, we switched to the
      pyrrolopyrimidine core which allowed functionalization on C-2. In addition, the
      modeling rationale was based on superimposing the structures of Aurora-A kinase
      and CDK2 which revealed enough differences leading to a path for selectivity
      improvement. The synthesis of the new series of pyrrolopyrimidine analogs relied
      on the development of a different route for the two key intermediates 7 and 19
      which led to analogs with both tunable activity against CDK1 and maintained cell
      potency.

PMID- 22607670
TI  - Interactions of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl
      acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas
      with dopamine D2 and 5-hydroxytryptamine 5HT(1A) receptors.
AB  - It is suggested that the ratio of dopamine D(2) to 5-hydroxytryptamine 5-HT(1A)
      activity is an important parameter that determines the efficiency of
      antipsychotic drugs. Here we present the synthesis of N-{[2-(4-phenyl-piperazin-1
      yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)
      ethyl]-phenyl}-3-aryl-2-yl-ureas and their structure-activity relationship
      studies on dopamine D(2) and 5-hydrohytryptamine 5-HT(1A) receptors. It was shown
      that ligand selectivity and affinity strongly depends on their topology and the
      presence of a pyridyl group in the head of molecules. Molecular modeling studies
      using homology modeling and docking simulation revealed a rational explanation
      for the ligand behavior. The observed binding modes and receptor-ligand
      interactions provided us with a clue for optimizing the optimal selectivity
      towards 5-HT(1A) receptors.

PMID- 22607671
TI  - Chromatin structure determines accessibility of a hairpin polyamide-chlorambucil
      conjugate at histone H4 genes in pancreatic cancer cells.
AB  - We have shown that a specific pyrrole-imidazole polyamide-DNA alkylator
      (chlorambucil) conjugate, 1R-Chl, alters the growth characteristics of various
      cancer cell lines in culture, and causes these cells to arrest in the G2/M stage
      of the cell cycle, without apparent cytotoxicity. This molecule has also shown
      efficacy in several mouse xenograft models, preventing tumor growth. Previous
      microarray studies have suggested that members of the histone H4 gene family, H4c
      and H4j/k, are the primary targets of this molecule, leading to reduced histone
      mRNA synthesis and growth arrest in cancer cells. In the present study, we
      examine the effects of 1R-Chl on transcription of other members of the H4 gene
      family, with the result that mRNA transcription of most genomic copies of H4 are
      down-regulated by 1R-Chl in a human pancreatic cancer cell line (MIA PaCa-2), but
      not in a cell line of non-cancerous origin (HEK293 cells). The basis for this
      differential effect is likely an open chromatin conformation within the H4 genes
      in cancer cells. Chromatin immunoprecipitation experiments show increased histone
      acetylation on the histone H4 genes in cancer cells, compared to HEK293 cells,
      explaining the differential activity of this molecule in cancer versus non-cancer
      cells.

PMID- 22607672
TI  - MK-8825: a potent and selective CGRP receptor antagonist with good oral activity
      in rats.
AB  - Rational modification of the clinically tested CGRP receptor antagonist MK-3207
      (3) afforded an analogue with increased unbound fraction in rat plasma and
      enhanced aqueous solubility, 2-[(8R)-8-(3,5-difluorophenyl)-8-methyl-10-oxo-6,9
      diazaspiro[4.5]dec-9-yl]-N-[(6S)-2'-oxo-1',2',5,7
      tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-3-yl]acetamide
      (MK-8825) (6). Compound 6 maintained similar affinity to 3 at the human and rat
      CGRP receptors but possessed significantly improved in vivo potency in a rat
      pharmacodynamic model. The overall profile of 6 indicates it should find utility
      as a rat tool to investigate effects of CGRP receptor blockade in vivo.

PMID- 22607674
TI  - Coumarin-trioxane hybrids: synthesis and evaluation as a new class of
      antimalarial scaffolds.
AB  - First synthesis of novel coumarin-trioxane hybrids is reported. The synthesis was
      achieved via condensation of beta-hydroxyhydroperoxides with coumarinic-aldehydes
      in presence of p-toluenesulfonic acid in good yields and the novel hybrids were
      evaluated for their antimalarial activity both in vitro and in vivo.

PMID- 22607673
TI  - Development of a novel, CNS-penetrant, metabotropic glutamate receptor 3 (mGlu3)
      NAM probe (ML289) derived from a closely related mGlu5 PAM.
AB  - Herein we report the discovery and SAR of a novel metabotropic glutamate receptor
      3 (mGlu(3)) NAM probe (ML289) with 15-fold selectivity versus mGlu(2). The
      mGlu(3) NAM was discovered via a 'molecular switch' from a closely related,
      potent mGlu(5) positive allosteric modulator (PAM), VU0092273. This NAM
      (VU0463597, ML289) displays an IC(50) value of 0.66 MUM and is inactive against
      mGlu(5).

PMID- 22607675
TI  - Development of a series of 3-hydroxyquinolin-2(1H)-ones as selective inhibitors
      of HIV-1 reverse transcriptase associated RNase H activity.
AB  - We report herein the synthesis of a series of 3-hydroxyquinolin-2(1H)-one
      derivatives. Esters and amide groups were introduced at position 4 of the basis
      scaffold and some modulations of the benzenic moiety were performed. Most
      compounds presented selective inhibitory properties in the 10-20 MUM range
      against HIV-1 reverse transcriptase associated ribonuclease H activity, without
      affecting the integrase and reverse transcriptase DNA polymerase activities.
      Unfortunately all tested compounds exhibited high cellular cytotoxicity in cell
      culture which limited their applications as antiviral agents.

PMID- 22607676
TI  - Synthesis and SAR of selective small molecule neuropeptide Y Y2 receptor
      antagonists.
AB  - Highly potent and selective small molecule neuropeptide Y Y2 receptor antagonists
      are reported. The systematic SAR exploration of a hit molecule N-(4-ethoxyphenyl)
      4-[hydroxy(diphenyl)methyl]piperidine-1-carbothioamide, identified from HTS, led
      to the discovery of highly potent NPY Y2 antagonists 16 (CYM 9484) and 54 (CYM
      9552) with IC(50) values of 19 nM and 12 nM respectively.

PMID- 22607677
TI  - Identification of chalcones as potent and selective PDE5A1 inhibitors.
AB  - Chalcones have an affinity for many receptors, enzymes, and transcription factors
      as flavonoid analogues. Their most studied pharmacological action is that of
      vasodilatation due to inhibition of phosphodiesterase 5A1 (PDE5A1). To this end,
      we have established a recursive partitioning model with 3 chemical descriptors
      for the prediction of compounds that can inhibit PDE5A1. This model was able to
      predict active compounds with an accuracy of 82.8%. Compound 4 was found to be a
      potent and selective inhibitor, with a relatively low IC(50) value. The binding
      mechanism of this compound was also investigated through molecular docking
      studies.

PMID- 22607678
TI  - An improved microwave assisted one-pot synthesis, and biological investigations
      of some novel aryldiazenyl chromeno fused pyrrolidines.
AB  - An improved microwave assisted one-pot method for the synthesis of twelve new
      aryldiazenylchromeno [4,3-b] pyrrolidines via intramolecular azomethine ylide
      cycloaddition route is described. The method is efficient and advantageous over
      conventional and solvent-free thermal methods. The stereochemistry of the
      compounds was confirmed on the basis of various NMR experiments, and finally by
      single crystal X-ray diffraction data. N-Methyl or ethyl pyrrolidine based
      heterocycles gave good biological activities.

PMID- 22607679
TI  - Synthesis and evaluation of [18F]Fluorobutyl ethacrynic amide: a potential PET
      tracer for studying glutathione transferase.
AB  - [(18)F]Flurobutyl ethacrynic amide ([(18)F]FBuEA) was prepared from the precursor
      tosylate N-Boc-N-[4-(toluenesulfonyloxy)butyl]ethacrynic amide with a
      radiochemical yield of 3%, a specific activity of 48 GBq/MUmol and radiochemical
      purity of 98%. Chemical conjugation of [(18)F]FBuEA with glutathione (GSH) via a
      self-coupling reaction and enzymatic conjugation under catalysis of
      glutathiontransferase alpha (GST-alpha) and pi provided about 41% yields of
      radiochemical conjugated product [(18)F]FBuEA-GSH, 85% and 5-16%, respectively.
      The catalytic selectivity of this tracer toward GST-alpha was addressed. Positron
      emission tomography (PET) imaging of [(18)F]FBuEA in normal rats showed that a
      homogeneous pattern of radioactivity was distributed in the liver, suggesting a
      catalytic role of GST. By contrast, PET images of [(18)F]FBuEA in rats with
      thioacetamide-induced cholangiocarcinoma displayed a heterogeneous pattern of
      radioactive accumulation with cold spots in tumor lesions. PET imaging with
      [(18)F]FBuEA could be used for early diagnosis of hepatic tumor with a low GST
      activity as well as liver function.

PMID- 22607681
TI  - Red fluorescent scaffold for highly sensitive protease activity probes.
AB  - We have developed a novel red fluorescent dye, 2Me SiR600 (lambda(em)=613 nm), in
      which the O atom of Rhodamine Green at the 10 position of the xanthene moiety is
      replaced with a Si atom, as a scaffold for probes to detect protease activity
      with extremely high S/N ratio. As proof of concept, we designed and synthesized
      probes for caspase-3 activity (Z-DEVD-SiR600) and leucine aminopeptidase activity
      (Leu-SiR600). Caspase-3-mediated cleavage of Z-DEVD-SiR600 resulted in a large
      bathochromic shift (93 nm) of the absorption maximum and a 432-fold fluorescence
      enhancement.

PMID- 22607680
TI  - Targeting prostate cancer cells with a multivalent PSMA inhibitor-guided
      streptavidin conjugate.
AB  - Prostate-specific membrane antigen (PSMA), a type II membrane glycoprotein, its
      high expression is associated with prostate cancer progression, and has been
      becoming an active target for imaging or therapeutic applications for prostate
      cancer. On the other hand, streptavidin-biotin system has been successfully
      employed in pretargeting therapy towards multiple cancers. Herein, we describe
      the synthesis of bifunctional ligands (biotin-CTT54, biotin-PEG(4)-CTT54, and
      biotin-PEG(12)-CTT54) possessing two functional motifs separated by a length
      varied polyethylene glycol (PEG) spacer: one (CTT54) binds tumor-marker PSMA and
      the other (biotin) binds streptavidin or avidin. All three compounds exhibited
      high potencies (IC(50) values: 1.21, 2.53, and 10nM, respectively) and
      irreversibility; but only biotin-PEG(12)-CTT54 demonstrated specifically labeling
      PSMA-positive prostate cancer cells in a two-step pretargeting procedure.
      Additionally, the pre-formulated complex between biotin-PEG(12)-CTT54 and Cy5
      streptavidin displayed the improved inhibitory potency (IC(50)=1.86 nM) and
      irreversibility against PSMA and rapid uptake of streptavidin conjugate into PSMA
      positive prostate cancer cells through PSMA-associated internalization. Together,
      all these results supported a proof-concept that combination of streptavidin and
      PSMA's biotinylated inhibitor may lead to development of a novel strategy of
      tumor-targeting imaging or drug delivery towards prostate cancer.

PMID- 22607682
TI  - Sulfonyl-morpholino-pyrimidines: SAR and development of a novel class of
      selective mTOR kinase inhibitor.
AB  - High throughput screening to identify inhibitors of the mTOR kinase revealed
      sulfonyl-morpholino-pyrimidine 1 as an attractive start point. The compound
      displayed good physicochemical properties and selectivity over related kinases
      such as PI3Kalpha. Library preparation of related analogs allowed the
      establishment of additional SAR understanding and in particular the requirement
      for a key hydrogen bond donor motif at the 4-position of the phenyl ring in
      compounds such as indole 19. Isosteric replacement of the indole functionality
      led to the identification of urea compounds such as 32 that show good levels of
      mTOR inhibition in both enzyme and cellular assays.

PMID- 22607683
TI  - 5-Cyano-6-oxo-1,6-dihydro-pyrimidines as potent antagonists targeting exchange
      proteins directly activated by cAMP.
AB  - Exchange proteins directly activated by cAMP (Epac) are a family of guanine
      nucleotide exchange factors that regulate a wide variety of intracellular
      processes in response to second messenger cAMP. To explore the structural
      determinants for Epac antagonist properties of high throughput screening (HTS)
      hit ESI-08, pyrimidine 1, a series of 5-cyano-6-oxo-1,6-dihydro-pyrimidine
      analogues have been synthesized and evaluated for their activities for Epac
      inhibition. Structure-activity relationship (SAR) analysis led to the
      identification of three more potent Epac antagonists (6b, 6g, and 6h). These
      inhibitors may serve as valuable pharmacological probes for further elucidation
      of the physiological functions and mechanisms of Epac regulation. Our SAR results
      and molecular docking studies have also revealed that further optimization of the
      moieties at the C-6 position of pyrimidine scaffold may allow us to discover more
      potent Epac-specific antagonists.

PMID- 22607684
TI  - 7-Azabicyclo[2.2.1]heptane as a scaffold for the development of selective sigma-2
      (sigma2) receptor ligands.
AB  - A series of N-substituted 7-azabicyclo[2.2.1]heptanes (12-17 and 22-25) and
      similarly substituted pyrrolidines (32-36 and 41-44) were synthesized as
      sterically-reduced, achiral analogs of adamantane- and trishomocubane-derived
      sigma ligands. In vitro competition binding assays against sigma receptors
      revealed that arylalkyl N-substituents conferred selectivity for the sigma(2)
      subtype, while alicyclic or polycarbocyclic substituents imparted high affinity
      for both subtypes. The sigma(2) binding and subtype selectivities of N-arylalkyl
      7-azanorbornanes was generally greater than the analogously-substituted
      pyrrolidines, indicating that steric bulk and conformational restriction around
      the nitrogen atom are likely important for subtype discrimination.

PMID- 22607685
TI  - Red cell distribution width improves the simplified acute physiology score for
      risk prediction in unselected critically ill patients.
AB  - INTRODUCTION: Recently, red cell distribution width (RDW), a measure of
      erythrocyte size variability, has been shown to be a prognostic marker in
      critical illness. The aim of this study was to investigate whether adding RDW has
      the potential to improve the prognostic performance of the simplified acute
      physiology score (SAPS) to predict short- and long-term mortality in an
      independent, large, and unselected population of intensive care unit (ICU)
      patients. METHODS: This observational cohort study includes 17,922 ICU patients
      with available RDW measurements from different types of ICUs. We modeled the
      association between RDW and mortality by using multivariable logistic regression,
      adjusting for demographic factors, comorbidities, hematocrit, and severity of
      illness by using the SAPS. RESULTS: ICU-, in-hospital-, and 1-year mortality
      rates in the 17,922 included patients were 7.6% (95% CI, 7.2 to 8.0), 11.2% (95%
      CI, 10.8 to 11.7), and 25.4% (95% CI, 24.8 to 26.1). RDW was significantly
      associated with in-hospital mortality (OR per 1% increase in RDW (95%CI)) (1.14
      (1.08 to 1.19), P < 0.0001), ICU mortality (1.10 (1.06 to 1.15), P < 0.0001), and
      1-year mortality (1.20 (95% CI, 1.14 to 1.26); P < 0.001). Adding RDW to SAPS
      significantly improved the AUC from 0.746 to 0.774 (P < 0.001) for in-hospital
      mortality and 0.793 to 0.805 (P < 0.001) for ICU mortality. Significant
      improvements in classification of SAPS were confirmed in reclassification
      analyses. Subgroups demonstrated robust results for gender, age categories, SAPS
      categories, anemia, hematocrit categories, and renal failure. CONCLUSIONS: RDW is
      a promising independent short- and long-term prognostic marker in ICU patients
      and significantly improves risk stratification of SAPS. Further research is
      needed the better to understand the pathophysiology underlying these effects.

PMID- 22607686
TI  - Encapsulation of alpha-1 antitrypsin in PLGA nanoparticles: in vitro
      characterization as an effective aerosol formulation in pulmonary diseases.
AB  - BACKGROUND: Alpha 1-antitrypsin (alpha1AT) belongs to the superfamily of serpins
      and inhibits different proteases. alpha1AT protects the lung from cellular
      inflammatory enzymes. In the absence of alpha1AT, the degradation of lung tissue
      results to pulmonary complications. The pulmonary route is a potent noninvasive
      route for systemic and local delivery. The aerosolized alpha1AT not only affects
      locally its main site of action but also avoids remaining in circulation for a
      long period of time in peripheral blood. Poly (D, L lactide-co glycolide) (PLGA)
      is a biodegradable and biocompatible polymer approved for sustained controlled
      release of peptides and proteins. The aim of this work was to prepare a wide
      range of particle size as a carrier of protein-loaded nanoparticles to deposit in
      different parts of the respiratory system especially in the deep lung. Various
      lactide to glycolide ratio of the copolymer was used to obtain different release
      profile of the drug which covers extended and rapid drug release in one
      formulation. RESULTS: Nonaqueous and double emulsion techniques were applied for
      the synthesis of nanoparticles. Nanoparticles were characterized in terms of
      surface morphology, size distribution, powder X-ray diffraction (XRD),
      encapsulation efficiency, in vitro drug release, FTIR spectroscopy and
      differential scanning calorimetry (DSC). To evaluate the nanoparticles
      cytotoxicity, cell cytotoxicity test was carried out on the Cor L105 human
      epithelial lung cancer cell line. Nanoparticles were spherical with an average
      size in the range of 100 nm to 1MU. The encapsulation efficiency was found to be
      higher when the double emulsion technique was applied. XRD and DSC results
      indicated that alpha1AT encapsulated in the nanoparticles existed in an amorphous
      or disordered-crystalline status in the polymer matrix. The lactic acid to
      glycolic acid ratio affects the release profile of alpha1AT. Hence, PLGA with a
      50:50 ratios exhibited the ability to release %60 of the drug within 8, but the
      polymer with a ratio of 75:25 had a continuous and longer release profile.
      Cytotoxicity studies showed that nanoparticles do not affect cell growth and were
      not toxic to cells. CONCLUSION: In summary, alpha1AT-loaded nanoparticles may be
      considered as a novel formulation for efficient treatment of many pulmonary
      diseases.

PMID- 22607687
TI  - Stereotactic body radiation therapy for reirradiation of localized adenocarcinoma
      of the pancreas.
AB  - BACKGROUND: Local control rates are poor in the treatment of pancreatic cancer.
      We investigated the role of hypofractionated stereotactic body radiation therapy
      (SBRT) for salvage or boost treatment after conventional doses of external beam
      radiation therapy. METHODS: All patients treated with SBRT for pancreatic
      adenocarcinoma at Georgetown University from June 2002 through July 2007 were
      examined. Eligible patients had prior external beam radiation therapy to the
      pancreas. Treatment parameters and clinical and radiographic follow-up were
      evaluated. RESULTS: Twenty-eight patients were identified who received SBRT after
      a median prior external beam radiotherapy dose of 50.4 Gy. The median patient age
      was 63 years old and the median follow-up was 5.9 months. Twelve of fourteen
      (85.7%) evaluable patients were free from local progression, with three partial
      responses and nine patients with stable disease. Toxicity consisted of one case
      of acute Grade II nausea/vomiting, and two cases of Grade III late GI toxicity.
      The median overall survival was 5.9 months, with 18% survival and 70% freedom
      from local progression at one year. CONCLUSIONS: Hypofractionated SBRT
      reirradiation of localized pancreatic cancer is a well-tolerated treatment. Most
      patients are free from local progression, albeit with limited follow-up, but
      overall survival remains poor.

PMID- 22607688
TI  - The IMPACT (Incident Management of Patients, Actions Centered on Treatment)
      program: a quality improvement approach for caring for patients initiating long
      term hemodialysis.
AB  - BACKGROUND: Patients beginning dialysis therapy are at risk of death and illness.
      The IMPACT (Incident Management of Patients, Actions Centered on Treatment)
      quality improvement program was developed to improve incident hemodialysis
      patient outcomes through standardized care. STUDY DESIGN: Quality improvement
      report. SETTING & PARTICIPANTS: Patients who started hemodialysis therapy between
      September 2007 and December 2008 at DaVita facilities using the IMPACT program (n
      = 1,212) constituted the intervention group. Propensity score-matched patients
      who initiated hemodialysis therapy in the same interval at DaVita facilities not
      using the IMPACT program (n = 2,424) made up the control group. QUALITY
      IMPROVEMENT PLAN: IMPACT intervention included a structured intake process and
      monitoring reports; patient enrollment in a 90-day patient education program and
      90-day patient management pathway. OUTCOMES: Mean dialysis adequacy (Kt/V),
      hemoglobin and albumin levels, percentage of patients using preferred vascular
      access (arteriovenous fistula or graft), and mortality at each quarter. RESULTS:
      Compared with the non-IMPACT group, the IMPACT group was associated with a higher
      proportion of patients dialyzing with a preferred access at 90 days (0.50 [95%
      CI, 0.47-0.53] vs 0.47 [95% CI, 0.45-0.49]; P = 0.1) and 360 days (0.63 [95% CI,
      0.61-0.66] vs 0.48 [95% CI, 0.46-0.50]; P < 0.001) and a lower mortality rate at
      90 days (24.8 [95% CI, 19.0-30.7] vs 31.9 [95% CI, 27.1-36.6] deaths/100 patient
      years; P = 0.08) and 360 days (17.8 [95% CI, 15.2-20.4] vs 25.1 [95% CI, 20.7
      25.2] deaths/100 patient-years; P = 0.01). LIMITATIONS: The study does not
      determine the care processes responsible for the improved outcomes. CONCLUSIONS:
      Intense management of incident dialysis patients with the IMPACT quality
      improvement program was associated with significantly decreased first-year
      mortality. Focused attention to the care of incident patients is an important
      part of a dialysis program.

PMID- 22607689
TI  - Louping ill in goats, Spain, 2011.
AB  - Although louping ill affects mainly sheep, a 2011 outbreak in northern Spain
      occurred among goats. Histopathologic lesions and molecular genetics identified a
      new strain of louping ill virus, 94% identical to the strain from Britain.
      Surveillance is needed to minimize risk to domestic and wildlife species and
      humans.

PMID- 22607691
TI  - Pneumococcal serotype-specific unresponsiveness in vaccinated child with cochlear
      implant.

PMID- 22607690
TI  - A genome-wide screen in human embryonic stem cells reveals novel sites of allele
      specific histone modification associated with known disease loci.
AB  - BACKGROUND: Chromatin structure at a given site can differ between chromosome
      copies in a cell, and such imbalances in chromatin structure have been shown to
      be important in understanding the molecular mechanisms controlling several
      disease loci. Human genetic variation, DNA methylation, and disease have been
      intensely studied, uncovering many sites of allele-specific DNA methylation
      (ASM). However, little is known about the genome-wide occurrence of sites of
      allele-specific histone modification (ASHM) and their relationship to human
      disease. The aim of this study was to investigate the extent and characteristics
      of sites of ASHM in human embryonic stem cells (hESCs). RESULTS: Using a
      statistically rigorous protocol, we investigated the genomic distribution of ASHM
      in hESCs, and their relationship to sites of allele-specific expression (ASE) and
      DNA methylation. We found that, although they were rare, sites of ASHM were
      substantially enriched at loci displaying ASE. Many were also found at known
      imprinted regions, hence sites of ASHM are likely to be better markers of
      imprinted regions than sites of ASM. We also found that sites of ASHM and ASE in
      hESCs colocalize at risk loci for developmental syndromes mediated by deletions,
      providing insights into the etiology of these disorders. CONCLUSION: These
      results demonstrate the potential importance of ASHM patterns in the
      interpretation of disease loci, and the protocol described provides a basis for
      similar studies of ASHM in other cell types to further our understanding of human
      disease susceptibility.

PMID- 22607692
TI  - Levamisole receptors: a second awakening.
AB  - Levamisole and pyrantel are old (1965) but useful anthelmintics that selectively
      activate nematode acetylcholine ion channel receptors; they are used to treat
      roundworm infections in humans and animals. Interest in their actions has surged,
      giving rise to new knowledge and technical advances, including an ability to
      reconstitute receptors that reveal more details of modes of action/resistance. We
      now know that the receptors are plastic and may form diverse species-dependent
      subtypes of receptor with different sensitivities to individual cholinergic
      anthelmintics. Understanding the biology of the levamisole receptors is expected
      to inform other studies on anthelmintics (ivermectin and emodepside) that act on
      ion channels.

PMID- 22607693
TI  - Malaria elimination: moving forward with spatial decision support systems.
AB  - Operational challenges facing contemporary malaria elimination have distinct
      geospatial elements including the need for high-resolution location-based
      surveillance, targeted prevention and response interventions, and effective
      delivery of essential services at optimum levels of coverage. Although mapping
      and geographical reconnaissance (GR) has traditionally played an important role
      in supporting malaria control and eradication, its full potential as an applied
      health systems tool has not yet been fully realised. As accessibility to global
      positioning system (GPS), geographic information system (GIS) and mobile
      computing technology increases, the role of an integrated spatial decision
      support system (SDSS) framework for supporting the increased operational demands
      of malaria elimination requires further exploration, validation and application;
      particularly in the context of resource-poor settings.

PMID- 22607694
TI  - Improving children's dairy food and calcium intake: can intervention work? A
      systematic review of the literature.
AB  - OBJECTIVE: Strategies are needed to address the shortfall in children's dairy
      food and Ca intakes. The present review identified interventions targeting an
      increase in children's dairy food or Ca intakes, and determined characteristics
      associated with successful intervention. DESIGN: A systematic literature search
      identified fourteen intervention studies, published in English, between 1990 and
      2010. Studies were evaluated for study population, setting and mode of delivery,
      dietary targets and outcome measures, measures of intervention intensity,
      intervention description, the use of behaviour change techniques and intervention
      effectiveness. SETTING: Interventions targeting an increase in dairy food or Ca
      intake. SUBJECTS: Children aged 5-12 years. RESULTS: Ten of the fourteen studies
      were considered to be effective. Studies focusing on encouraging intake of dairy
      foods or Ca alone were all effective, compared with 55 % of studies promoting
      dairy within the context of a healthy diet. Effective interventions tended to be
      higher in intensity, provide dairy foods and were delivered across a variety of
      settings to a range of primary targets. The number of behaviour change techniques
      used did not differentiate effective and ineffective interventions, but the use
      of taste exposure and prompting practice appeared to be important for effective
      intervention. CONCLUSIONS: Interventions that target an increase in children's
      dairy food or Ca intake could potentially increase children's dairy food intake
      by about one serving daily. Research conducted outside the USA is needed. The
      review has identified some promising strategies likely to be part of effective
      interventions for improving dairy and Ca intakes in countries where children's
      intake is insufficient.

PMID- 22607695
TI  - Early protective effect of total hypoxic preconditioning on rats against systemic
      injury from hemorrhagic shock and resuscitation.
AB  - BACKGROUND: In vivo or in vitro hypoxic preconditioning (HPC) can protect various
      tissues and cells against subsequent ischemia and/or reperfusion (hypoxia and/or
      reoxygenation) injury. Total HPC (THPC) in animal models is largely aimed at
      protecting single organs; however, scant data exist on whole body protection. The
      present study investigated whether THPC could protect anesthetized rats against
      the systemic injury induced by hemorrhagic shock and resuscitation (HS/R).
      METHODS: The 4-cycle THPC protocol consisted of 5 min of inhalation hypoxia
      (fraction of inspired oxygen 10%, N(2) 90% plus oxygen 10%) followed by 10 min of
      inhalation air (oxygen 21%). An acute HS/R model of anesthetized rats was used.
      The experiment was divided into two parts of the Severe HS/R and Moderate HS/R,
      differentiated by a shed blood volume of 60% or 50% (HS/R(60%) or HS/R(50%),
      respectively) of the total blood volume of rats, respectively. In the Severe HS/R
      part, the heart rate, respiration rate, and mean arterial pressure of the rats
      were measured, and the survival of the rats was observed. We examined the
      pathomorphologic changes in the vital organs of rats and measured the arterial
      blood gas, heart rate, respiration rate, and mean arterial pressure of the rats
      in the Moderate HS/R part. RESULTS: THPC did not result in irreversible changes
      or death in the rats. The rats in the THPC + HS(60%)/R group had a significantly
      greater survival rate than those in the HS(60%)/R group (59% versus 33%, log-rank
      test, chi-square = 4.356, P = 0.037). The histopathologic lung score of the rats
      in the HS(50%)/R group (1.7 +/- 0.5) was significantly greater than that in the
      THPC + HS(50%)/R (1.1 +/- 0.6, P = 0.046). The arterial blood gas pH was lower in
      the HS(50%)/R group than in the THPC + HS(50%)/R group. THPC had a greater
      influence on the arterial partial pressure of oxygen and carbon dioxide than on
      bicarbonate radical and base excess. The respiration rate in the THPC + HS/R
      group was faster than that in the HS/R group. No significant differences in heart
      rate or mean arterial pressure were seen between the THPC + HS/R and HS/R groups.
      CONCLUSIONS: In anesthetized rats, THPC provided early protection against the
      subsequent systemic injury caused by hemorrhagic shock following resuscitation.
      THPC might exert systemic protection by improving the function of vital organs
      (e.g., lungs and, perhaps, the brain).

PMID- 22607696
TI  - Best temperature for static liver graft storage is 1 degrees C.
AB  - BACKGROUND: The best storage temperature in liver transplantation remains an
      unsolved question. METHODS: After storage for 24h in University of Wisconsin
      solution at +4 degrees C, +1 degrees C, or -0.5 degrees C, rat livers were
      subjected, or not, to 15min of warm ischemia, rinsed with Ringer lactate, and
      subsequently reperfused with oxygenated Krebs-Henseleit buffer. RESULTS: In the
      presence of warm ischemia, for livers stored at +4 degrees C, creatine kinase
      (CK) peaked at 21+/-5IUg(-1)h(-1), hepatic resistance at 34,700+/-1500dynscm(-5),
      bile flow reached 18+/-4MULg(-1)h(-1) after 10min, and oxygen consumption
      stabilized at about 25MUmolg(-1)h(-1) after 20min. When livers were stored at +1
      degrees C, CK and hepatic resistance were lowered, bile production was 33+/
      6MULg(-1)h(-1) (P<0.05 versus +4 degrees C), and oxygen consumption was 105+/
      10MUmolg(-1)h(-1) (P<0.001). For livers stored at-0.5 degrees C, results were not
      statistically different from those of the +1 degrees C group except for bile
      flow, which was significantly lower. Without warm ischemia, the peak of CK
      (P=0.015) and the peak hepatic resistance (P<0.001) of the +4 degrees C group
      were significantly increased compared with the +1 degrees C or -0.5 degrees C
      groups. However, no difference in bile flow or oxygen consumption was observed.
      The number of trypan blue-positive nonparenchymal cells (P=0.003) and the gain in
      liver weight during the reperfusion (P=0.015) were minimal after storage at +1
      degrees C. CONCLUSIONS: Static storage at +1 degrees C improved liver function
      compared with +4 degrees C or -0.5 degrees C. Main beneficial effect was observed
      with parameters reflecting sinusoidal cells injury.

PMID- 22607697
TI  - Implications of binding mode and active site flexibility for inhibitor potency
      against the salicylate synthase from Mycobacterium tuberculosis.
AB  - MbtI is the salicylate synthase that catalyzes the first committed step in the
      synthesis of the iron chelating compound mycobactin in Mycobacterium
      tuberculosis. We previously developed a series of aromatic inhibitors against
      MbtI based on the reaction intermediate for this enzyme, isochorismate. The most
      potent of these inhibitors had hydrophobic substituents, ranging in size from a
      methyl to a phenyl group, appended to the terminal alkene of the enolpyruvyl
      group. These compounds exhibited low micromolar inhibition constants against MbtI
      and were at least an order of magnitude more potent than the parental compound
      for the series, which carries a native enolpyruvyl group. In this study, we
      sought to understand how the substituted enolpyruvyl group confers greater
      potency, by determining cocrystal structures of MbtI with six inhibitors from the
      series. A switch in binding mode at the MbtI active site is observed for
      inhibitors carrying a substituted enolpyruvyl group, relative to the parental
      compound. Computational studies suggest that the change in binding mode, and
      higher potency, is due to the effect of the substituents on the conformational
      landscape of the core inhibitor structure. The crystal structures and
      fluorescence-based thermal shift assays indicate that substituents larger than a
      methyl group are accommodated in the MbtI active site through significant but
      localized flexibility in the peptide backbone. These findings have implications
      for the design of improved inhibitors of MbtI, as well as other chorismate
      utilizing enzymes from this family.

PMID- 22607699
TI  - Trichloroethylene overexposure in an automotive stamping facility.

PMID- 22607698
TI  - The European quality of care pathways (EQCP) study on the impact of care pathways
      on interprofessional teamwork in an acute hospital setting: study protocol: for a
      cluster randomised controlled trial and evaluation of implementation processes.
AB  - BACKGROUND: Although care pathways are often said to promote teamwork, high-level
      evidence that supports this statement is lacking. Furthermore, knowledge on
      conditions and facilitators for successful pathway implementation is scarce. The
      objective of the European Quality of Care Pathway (EQCP) study is therefore to
      study the impact of care pathways on interprofessional teamwork and to build up
      understanding on the implementation process. METHODS/DESIGN: An international
      post-test-only cluster Randomised Controlled Trial (cRCT), combined with process
      evaluations, will be performed in Belgium, Ireland, Italy, and Portugal. Teams
      caring for proximal femur fracture (PFF) patients and patients hospitalized with
      an exacerbation of chronic obstructive pulmonary disease (COPD) will be
      randomised into an intervention and control group. The intervention group will
      implement a care pathway for PFF or COPD containing three active components: a
      formative evaluation of the actual teams' performance, a set of evidence-based
      key interventions, and a training in care pathway-development. The control group
      will provide usual care. A set of team input, process and output indicators will
      be used as effect measures. The main outcome indicator will be relational
      coordination. Next to these, process measures during and after pathway
      development will be used to evaluate the implementation processes. In total, 132
      teams have agreed to participate, of which 68 were randomly assigned to the
      intervention group and 64 to the control group. Based on power analysis, a sample
      of 475 team members per arm is required. To analyze results, multilevel analysis
      will be performed. DISCUSSION: Results from our study will enhance understanding
      on the active components of care pathways. Through this, preferred implementation
      strategies can be defined.

PMID- 22607700
TI  - GATA binding protein 3 is down-regulated in bladder cancer yet strong expression
      is an independent predictor of poor prognosis in invasive tumor.
AB  - Although GATA binding protein 3, a zinc finger transcription factor and an
      estrogen receptor-regulated gene, has recently been suggested as a marker for
      urothelium, prognostic significance of GATA binding protein 3 expression in
      bladder tumor remains unclear. We immunohistochemically stained for GATA binding
      protein 3 in urothelial neoplasm and matched nonneoplastic bladder tissue
      specimens. GATA binding protein 3 was positive in 125 (86%; 13 [9%] weak, 44
      [30%] moderate, and 68 [47%] strong) of 145 bladder tumors, which was
      significantly lower than in benign urothelium (104/106 [98%]; 3 [3%] weak, 30
      [28%] moderate, and 71 [67%] strong) (P=.001). Fifty (98%) of 51 low-grade tumors
      were GATA binding protein 3 positive, whereas 75 (80%) of 94 high-grade
      carcinomas were GATA binding protein 3 positive (P=.002). Similarly, 78 (98%) of
      80 non-muscle-invasive tumors expressed the GATA binding protein 3, compared with
      47 (72%) of 65 muscle-invasive tumors (P<.001). Conversely, among 68 cases
      treated with cystectomy, significantly lower expression of GATA binding protein 3
      was found in pN0 tumors (32/47 [68%]) than in node-positive tumors (20/21 [95%])
      (P=.027). Kaplan-Meier and log-rank tests further revealed that overall
      positivity (P=.048) or strong positivity (P=.025) of GATA binding protein 3
      correlated with progression of muscle-invasive tumors. Multivariate analysis
      identified high GATA binding protein 3 expression as a strong prognosticator for
      progression (P=.052) and cancer-specific survival (P=.040) of muscle-invasive
      tumors. Moreover, there were significant correlations between GATA binding
      protein 3 expression vs androgen receptor overexpression, estrogen receptor alpha
      overexpression, or loss of estrogen receptor beta expression. Thus, compared with
      benign urothelium, a significant decrease in the expression of GATA binding
      protein 3 in urothelial neoplasms was seen. Loss of GATA binding protein 3 was
      associated with high-grade and/or muscle-invasive tumors, whereas strong
      expression was an independent predictor of poor prognosis.

PMID- 22607701
TI  - Hyalinized stroma in clear cell carcinoma of the ovary: how is it formed?
AB  - Ovarian clear cell carcinoma often shows stromal hyalinization. The main
      constituents of hyalinization are basement membrane materials, including laminin
      and type IV collagen. Although it is known that clear cell carcinoma cells
      produce these materials, it remains unclear whether they can form hyalinized
      stroma by themselves or if cooperation with stromal cells is required. In the
      present study, we first reviewed 35 surgical specimens for the pattern of early
      hyalinization. It occurred either in a globule-like pattern or in a
      circumferential pattern. In the former, compact hyaline globules abruptly
      appeared within tumor cell aggregates. In the latter, hyalinized materials
      appeared around the preceding spherule-like mucoid spaces among tumor cells. In
      either pattern, hyalinization is most likely to begin in the intercellular spaces
      among tumor cells, where stromal cells rarely intervene. To verify this, 2
      ovarian clear cell carcinoma cell lines (JHOC-5 and HAC-2) were analyzed in
      vitro. Each cell line was monocultured in suspension: if any deposition occurred
      in floating multicellular aggregates, it should be in the intercellular spaces.
      Deposition of type IV collagen occurred in a globule-like pattern (JHOC-5) or a
      circumferential pattern (HAC-2) within multicellular aggregates, and it developed
      into a structure comparable with the hyalinized stroma in surgical specimens.
      Intercellular deposition of type IV collagen was reproduced by culture in 3
      dimensional type I collagen gels. All of these findings showed that clear cell
      carcinoma cells themselves form hyalinized stroma by depositing self-made
      basement membrane materials in the intercellular spaces.

PMID- 22607702
TI  - Immunohistochemical and oncogenetic analyses of the esophageal basaloid squamous
      cell carcinoma in comparison with conventional squamous cell carcinomas.
AB  - Basaloid squamous cell carcinoma of the esophagus is a rare variant of squamous
      cell carcinoma. We reviewed 878 cases of esophageal squamous cell carcinoma and
      detected 22 cases (3%) of basaloid squamous cell carcinoma. These tumors and
      stage-matched paired conventional squamous cell carcinomas were investigated for
      clinicopathologic features and immunoreactivity of cytokeratin subtypes, p53, B
      cell lymphoma 2 (bcl-2), beta-catenin, and epidermal growth factor receptor.
      Molecular aberrations in p53, CTNNB1 (the gene encoding beta-catenin), and
      epidermal growth factor receptor (EGFR) were also determined. Patients with
      basaloid squamous cell carcinomas demonstrated a 5-year survival rate of 42%,
      significantly worse than those with well-differentiated squamous cell carcinoma
      (P<.01). Histologically, solid nests with central necrosis and a cribriform
      pattern were identified in almost all (>=95%) cases, and ductal differentiation
      was less frequent (45%) but associated with significantly better survival
      (P<.05). Compared with conventional squamous cell carcinomas, the basaloid
      squamous cell carcinomas were less immunoreactive for cytokeratin 14, cytokeratin
      903, and membranous beta-catenin (P<.01-.001) but more reactive for bcl-2,
      nuclear beta-catenin, epidermal growth factor receptor, and Ki-67 (P<.05-.001).
      Direct sequencing showed mutations of p53 (36%), EGFR (14%), but not CTNNB1;
      fluorescent in situ hybridization detected amplification of the epidermal growth
      factor receptor gene (22%). In basaloid squamous cell carcinomas, low-level
      expression of cytokeratin 14/cytokeratin 903 and mutations of p53 and EGFR had a
      significant influence on worse survival (P<.05-.001). We conclude that the
      esophageal basaloid squamous cell carcinoma, a neoplasm with particularly
      aggressive biologic behavior, should be differentiated from conventional squamous
      cell carcinomas. In this context, immunohistochemical assessment of several
      markers might provide a useful adjunct diagnostic tool. Aberrations of p53 and
      epidermal growth factor receptor genes are possibly involved in progression of
      esophageal basaloid squamous cell carcinoma.

PMID- 22607703
TI  - Follicular lymphoma with prominent Dutcher body formation: a pathologic study of
      3 cases in comparison with nodal or splenic lymphoplasmacytic lymphoma and
      marginal zone lymphoma.
AB  - Dutcher bodies have been described in lymphoid neoplasms with plasmacytic
      differentiation, including plasma cell myeloma, lymphoplasmacytic lymphoma, and
      marginal zone lymphoma. We report a pathologic study of 3 cases of follicular
      lymphoma with extensive Dutcher body formation in comparison with
      lymphoplasmacytic lymphoma and marginal zone lymphoma. Of 3 cases, 1 showed a
      follicular growth pattern, whereas the other 2 cases demonstrated only a vague
      nodular appearance highlighted by immunohistochemical analysis. Cells containing
      Dutcher bodies were counted at 25, 90, or 110 per high-power field in each case,
      respectively. In 2 cases, cells with Dutcher bodies were clustered in an
      intrafollicular distribution, a possible histopathologic clue for follicular
      lymphoma. Immunoglobulin M kappa was identified as the component of Dutcher
      bodies in all 3 cases, implying a possible molecular basis for the formation of
      Dutcher bodies in B-cell lymphomas. All 3 cases had cytogenetic changes
      supporting the diagnosis of follicular lymphoma, including dual rearrangement of
      BCL2 and BCL6, rearrangement of BCL2 with trisomy 3 (BCL6), and isolated BCL6
      rearrangement. We emphasize immunohistochemical analyses with anti-kappa/lambda
      and anti-immunoglobulin heavy-chain isotypes to characterize Dutcher bodies and
      document clonality in addition to the routine lymphoma workup and indicated
      cytogenetic studies in B-cell lymphomas with prominent Dutcher bodies.

PMID- 22607704
TI  - Vigilin interacts with signal peptide peptidase.
AB  - BACKGROUND: Signal peptide peptidase (SPP), a member of the presenilin-like intra
      membrane cleaving aspartyl protease family, migrates on Blue Native (BN) gels as
      100 kDa, 200 kDa and 450 kDa species. SPP has recently been implicated in other
      non-proteolytic functions such as retro-translocation of MHC Class I molecules
      and binding of misfolded proteins in the endoplasmic reticulum (ER). These high
      molecular weight SPP complexes might contain additional proteins that regulate
      the proteolytic activity of SPP or support its non-catalytic functions. RESULTS:
      In this study, an unbiased iTRAQ-labeling mass spectrometry approach was used to
      identify SPP-interacting proteins. We found that vigilin, a ubiquitous multi-KH
      domain containing cytoplasmic protein involved in RNA binding and protein
      translation control, selectively enriched with SPP. Vigilin interacted with SPP
      and both proteins co-localized in restricted intracellular domains near the ER,
      biochemically co-fractionated and were part of the same 450 kDa complex on BN
      gels. However, vigilin does not alter the protease activity of SPP, suggesting
      that the SPP-vigilin interaction might be involved in the non-proteolytic
      functions of SPP. CONCLUSIONS: We have identified and validated vigilin as a
      novel interacting partner of SPP that could play an important role in the non
      proteolytic functions of SPP. This data adds further weight to the idea that
      intramembrane-cleaving aspartyl proteases, such as presenilin and SPPs, could
      have other functions besides the proteolysis of short membrane stubs.

PMID- 22607705
TI  - Staged reduction of neglected transscaphoid perilunate fracture dislocation: a
      report of 16 cases.
AB  - BACKGROUND: Transscaphoid perilunate fracture dislocation is a rare injury and
      can be easily missed at the initial treatment. Once ignored, late reduction is
      not possible and needs extensive dissection. An alternative treatment such as
      proximal row carpectomy may be required for neglected injuries, but surgical
      outcome is not as good as that of an early reduction. We aim to present an
      alternative technique of staged reduction and fixation in patients of neglected
      transscaphoid perilunate dislocations and study its outcome. MATERIAL & METHODS:
      16 cases (14 males & 2 females) with neglected transscaphoid perilunate fracture
      dislocation (> 3 month old) were treated with staged reduction. Mean duration
      between injury and surgery was 4.5 months. In first stage an external fixator was
      applied across the wrist and distraction was done at 1 mm/day. Second surgery was
      done through dorsal approach and we were able to reduce all the fractures &
      dislocations. Herbert screws and K wires were used for fixation. RESULTS: The
      mean duration between two surgeries was 2.4 weeks (range 2-4 weeks). 9 cases had
      excellent results, 5 had good result. Two patients developed reflex sympathetic
      dystrophy and had fair results. CONCLUSION: Staged reduction should be considered
      for neglected transscaphoid perilunate dislocations. If properly executed, a good
      functional pain free range of motion is the usual outcome.

PMID- 22607706
TI  - African swine fever virus strain Georgia 2007/1 in Ornithodoros erraticus ticks.

PMID- 22607707
TI  - Accuracy of ICD-10 codes for surveillance of Clostridium difficile infections,
      France.
AB  - The sensitivity and specificity of surveillance for Clostridium difficile
      infections according to International Classification of Diseases, 10th revision,
      codes were compared with laboratory results as standard. Sensitivity was 35.6%;
      specificity was 99.9%. Concordance between the 2 methods was moderate.
      Surveillance based on ICD-10 codes underestimated the rate based on laboratory
      results.

PMID- 22607708
TI  - An examination of environmental correlates with childhood height-for-age in
      Ghana.
AB  - OBJECTIVE: The relationship between a child's environment and nutritional status
      is difficult to examine yet could offer an important guide to policy. The
      objective of the present work was to examine individual and environmental
      correlates with childhood height-for-age in Ghana. DESIGN: Data were derived from
      the 2008 MEASURE Demographic and Health Survey in Ghana, the 2000 Ghana
      Population and Housing Census, and the World Wide Fund for Nature's eco-regions
      database. A generalized linear mixed regression model was used to estimate the
      effects of individual and environmental correlates on height-for-age. SUBJECTS:
      The study examined 2225 Ghanaian children aged 0-59 months. SETTING: The setting
      was all districts in Ghana for the year 2008. RESULTS: After accounting for
      individual characteristics of children, mothers and households, height-for-age
      was significantly associated with population density. Other significantly
      associated variables in the final model were the age of the child, vaccination
      status, the size of the child at birth, months of breast-feeding, mother's BMI,
      whether the child's mother had health insurance and wealth quintile. CONCLUSIONS:
      In addition to a number of characteristics of the children and their households,
      the social milieu is important to understanding differences in height-for-age
      among children in Ghana. The biophysical environment was not associated with
      height-for-age.

PMID- 22607710
TI  - The case for including reach as a key element of program theory.
AB  - This paper suggests that there is a need to build reach in the logic models and
      results frameworks of public health initiatives. A lack of explicit thinking
      about reach in logic models can lead to problems such as narrow/constricted
      understanding of impacts chain, favoring of 'narrow and efficient' initiatives
      over 'wide and engaging' initiatives and biased thinking against equity
      considerations. An alternative approach described in this paper that explicitly
      considers reach demonstrates that an explicit description of reach in program
      theory and results logic depictions can improve equity in health and social
      systems.

PMID- 22607709
TI  - Down-regulation of the PI3K/Akt signaling pathway and induction of apoptosis in
      CA46 Burkitt lymphoma cells by baicalin.
AB  - BACKGROUND: Baicalin, a flavone present in Scutellaria baicalensis Georgi,
      inhibits the growth of human leukemia and myeloma cells through induction of
      apoptosis. METHODS: The present study was undertaken to ascertain whether
      cultured Burkitt lymphoma cells undergo apoptosis when treated with baicalin.
      Growth rates were measured using MTT and colony formation assays, and induction
      of apoptosis was quantified using Annexin V and DNA fragmentation assays.
      Mechanisms underlying observed growth suppression were examined using Western
      blotting. RESULTS: Treatment of CA46 Burkitt lymphoma cells with baicalin for 48
      h markedly decreased the rate of cell proliferation; an IC50 value of 10 MUM was
      obtained. Colony formation was almost fully suppressed at 10 MUM baicalin. CA46
      cells underwent apoptosis in response to baicalin treatment as evidenced by an
      increase in the percentage of cells stainable with Annexin V, by increased DNA
      fragmentation, and by activation of the intrinsic (mitochondrial) pathway for
      cell death as characterized by increased expression of the cleaved forms of
      caspase-9, caspase-3, and poly (ADP-ribose) polymerase. Additionally, baicalin
      was found to down-regulate anti-apoptotic and up-regulate apoptotic components of
      the phosphatidylinositide-3-kinase (PI3K)/serine/threonine kinase (Akt) signaling
      pathway. CONCLUSIONS: The concentrations at which baicalin altered expression of
      components of the PI3K/Akt pathway in CA46 cells were comparable to those that
      suppressed growth and induced apoptosis, supporting the hypothesis that the
      observed growth-inhibitory and apoptosis-inducing actions of baicalin in these
      cells are mediated by down-regulation of this pathway.

PMID- 22607711
TI  - A technical improvement in retropharyngeal carotid reconstruction.
AB  - The carotid-carotid bypass via a retropharyngeal tunnel enables treating proximal
      occlusions. With reference to two clinical cases, we present a technique that
      consists of transposition of one of the carotid arteries to contralateral
      position, avoiding simultaneous clamping of both carotids.

PMID- 22607712
TI  - A "fall-back" technique for difficult inferior vena cava filter retrieval.
AB  - OBJECTIVE: The purpose of this study was to describe the results of an
      alternative technique for inferior vena cava filter (IVCF) retrieval that can be
      used when the retrieval hook cannot be snared. METHODS: Retrospective review of
      all patients undergoing attempted IVCF retrieval by a single surgeon between
      March 2009 and March 2011 was undertaken. After December 2009, in cases where the
      retrieval hook could not be snared, an 18F/85 cm sheath was inserted into the
      internal jugular vein and a Bentson wire (Cook Medical, Bloomington, Ind) and
      snare were advanced across separate interstices of the filter. The resulting
      "lasso" was pulled up below the collar at the top of the filter, and the filter
      collapsed into the sheath. RESULTS: Over 28 months, 34 patients underwent
      attempted retrieval of Gunther Tulip filters (Cook Medical). Patients were 44+/
      15 years old; 59% were women (n=20). Filters were placed for venous
      thromboembolism with contraindication to anticoagulation in seven cases and
      prophylactically in 27 cases. Of the prophylactic cases, 18 (67%) were placed
      before planned bariatric surgery. Before December 2009, the success rate was 86%
      (6 of 7): the retrieval hook of one filter could not be snared and seemed to be
      embedded in the wall of the cava. After adoption of the described technique, the
      success rate was 96% (26 of 27): one patient refused further attempts at central
      venous catheterization after multiple unsuccessful attempts. Filters retrieved
      conventionally by snaring the hook (n=18) were implanted on average for 4.8+/-3.7
      months and 12.1+/-10.1 months for those retrieved using the new technique (n=14;
      P=.02). All patients were discharged on the day of the procedure without
      complication. The one patient in whom the retrieval hook could not be snared
      before December 2009 has refused another attempt at retrieval. CONCLUSIONS: The
      method of IVCF retrieval described here was successful in every instance in which
      it was attempted. It was associated with no morbidity despite the customary use
      of an 18F sheath in the internal jugular vein. The approach constitutes an
      appropriate "fall-back" technique when the retrieval hook of a removable IVCF
      cannot be snared.

PMID- 22607714
TI  - Use of body mass index percentile to identify fat-free mass depletion in children
      with cystic fibrosis.
AB  - BACKGROUND & AIMS: Nutritional failure in children with cystic fibrosis (CF) has
      a negative effect on their morbidity and survival. It is unknown if determination
      of fat-free mass is a better screening method for nutritional failure than the
      currently recommended body mass index (BMI) alone. METHODS: This cross-sectional
      study in 77 children with CF (age: 14.8 +/- 2.9 y) measured fat-free mass, fat
      mass, bone mineral content and density using dual-energy X-ray absorptiometry.
      Nutritional failure was defined as BMI <10 percentile and/or fat-free mass index
      <5th percentile. Statistics were done using ANOVA and t-tests. RESULTS: Thirty
      one percent (31%) of the patients with CF was characterized by nutritional
      failure, and 14% had low fat-free mass index with preserved values for BMI
      (hidden depletion). Only 52% of the patients with fat-free mass depletion was
      detected when using the criteria BMI <10 percentile. Patients with fat-free mass
      depletion had reduced values for forced expiratory volume in 1 s (FEV(1)),
      independent of body mass index (P < 0.05), and lower values for bone mineral
      density in whole body, spine and hip, and spine bone mineral apparent density (P
      < 0.01). BMI <=20 percentile was associated with a large drop in fat-free mass, a
      reduced FEV(1), and in bone mineral loss. CONCLUSIONS: Depletion of fat-free mass
      enhances morbidity in children with CF and is undetected in many of these
      children when only BMI percentile is used as screening method. BMI percentile of
      20 should be considered as the new critical threshold for nutritional failure in
      CF if body composition techniques are not available.

PMID- 22607713
TI  - Investigation of essential trace and toxic elements in biological samples (blood,
      serum and scalp hair) of liver cirrhotic/cancer female patients before and after
      mineral supplementation.
AB  - BACKGROUND & AIMS: The aim of present study was to compare the levels of
      essential trace and toxic elements in biological samples (blood, serum and scalp
      hair) of female liver cirrhotic/cancer patients (n = 132), of two age groups (20
      45 years) and (46-60 years), before and after sixty days treatment with mineral
      supplementation. For comparison purpose, same biological samples were also
      collected from healthy female subjects (n = 75) of same age groups. METHODS: The
      biological samples were oxidized by 65% HNO(3): 30% H(2)O(2) (2:1) in microwave
      oven. The digests of all biological samples were analyzed for arsenic (As),
      cadmium (Cd), selenium (Se) and zinc (Zn) by electrothermal atomic absorption
      spectrometry. RESULTS: The levels of Se and Zn were lower in liver
      cirrhotic/cancer patients as compared to healthy individuals (p < 0.001). The
      patients of liver cirrhosis/cancer have two folds higher As and Cd levels in
      biological samples as related to age matched referents. Moreover, negative
      correlation was observed between essential and toxic elements. CONCLUSIONS: The
      pathogenesis of liver cirrhosis/cancer has been associated with changes in the
      balance of certain essential trace and toxic elements. It was observed that the
      status of Se and Zn in addition to some biochemical parameters was improved in
      biological samples of both groups of patients after sixty days treatment with
      mineral supplementation.

PMID- 22607715
TI  - Is non-union of tibial shaft fractures due to nonculturable bacterial pathogens?
      A clinical investigation using PCR and culture techniques.
AB  - BACKGROUND: Non-union continues to be one of the orthopedist's greatest
      challenges. Despite effective culture methods, the detection of low-grade
      infection in patients with non-union following tibial fracture still presents a
      challenge. We investigated whether "aseptic" tibial non-union can be the result
      of an unrecognized infection. METHODS: A total of 23 patients with non-union
      following tibial shaft fractures without clinical signs of infection were
      investigated. Intraoperative biopsy samples obtained from the non-union site were
      examined by means of routine culture methods and by polymerase chain reaction
      (PCR) for the detection of 16 S ribosomal RNA (rRNA). Control subjects included
      12 patients with tibial shaft fractures. RESULTS: 23 patients (8 women and 15
      men; mean age: 47.4 years) were included into this study. Preoperative C-reactive
      protein levels (mean: 20.8 mg/l) and WBC counts (mean: 8,359/MUl) in the study
      group were not significantly higher than in the control group. None of the
      samples of non-union routine cultures yielded microorganism growth. Bacterial
      isolates were found by conventional culturing methods in only 1 case of an open
      fracture from the control group. In this case, PCR yielded negative results. 16 S
      rRNA was detected in tissue specimens from 2 patients (8.7%) with non-union. The
      analysis of these variable species-specific sequences enabled the identification
      of specific microorganisms (1x Methylobacterium species, 1x Staphylococcus
      species). Both PCR-positive patients were culture-negative. CONCLUSIONS: The
      combination of microbiological culture and broad-range PCR seems to substantially
      add to the number of microbiological diagnoses obtained and may improve the
      clinician's ability to tailor therapy to the individual patient's needs.

PMID- 22607716
TI  - The impact of comorbid cannabis and methamphetamine use on mental health among
      regular ecstasy users.
AB  - OBJECTIVE: Residual effects of ecstasy use induce neurotransmitter changes that
      make it biologically plausible that extended use of the drug may induce
      psychological distress. However, there has been only mixed support for this in
      the literature. The presence of polysubstance use is a confounding factor. The
      aim of this study was to investigate whether regular cannabis and/or regular
      methamphetamine use confers additional risk of poor mental health and high levels
      of psychological distress, beyond regular ecstasy use alone. METHOD: Three years
      of data from a yearly, cross-sectional, quantitative survey of Australian regular
      ecstasy users was examined. Participants were divided into four groups according
      to whether they regularly (at least monthly) used ecstasy only (n=936), ecstasy
      and weekly cannabis (n=697), ecstasy and weekly methamphetamine (n=108) or
      ecstasy, weekly cannabis and weekly methamphetamine (n=180). Self-reported mental
      health problems and Kessler Psychological Distress Scale (K10) were examined.
      RESULTS: Approximately one-fifth of participants self-reported at least one
      mental health problem, most commonly depression and anxiety. The addition of
      regular cannabis and/or methamphetamine use substantially increases the
      likelihood of self-reported mental health problems, particularly with regard to
      paranoia, over regular ecstasy use alone. Regular cannabis use remained
      significantly associated with self reported mental health problems even when
      other differences between groups were accounted for. Regular cannabis and
      methamphetamine use was also associated with earlier initiation to ecstasy use.
      CONCLUSIONS: These findings suggest that patterns of drug use can help identify
      at risk groups that could benefit from targeted approaches in education and
      interventions. Given that early initiation to substance use was more common in
      those with regular cannabis and methamphetamine use and given that this group had
      a higher likelihood of mental health problems, work around delaying onset of
      initiation should continue to be a priority.

PMID- 22607717
TI  - Molecular epidemiology of Laguna Negra virus, Mato Grosso State, Brazil.
AB  - We associated Laguna Negra virus with hantavirus pulmonary syndrome in Mato
      Grosso State, Brazil, and a previously unidentified potential host, the Calomys
      callidus rodent. Genetic testing revealed homologous sequencing in specimens from
      20 humans and 8 mice. Further epidemiologic studies may lead to control of HPS in
      Mato Grosso State.

PMID- 22607718
TI  - Iodine status of pregnant women in a population changing from high to lower fish
      and milk consumption.
AB  - OBJECTIVES: Pregnancy is one of the most critical periods for iodine deficiency.
      The aim of the present study was to assess the iodine status and dietary intake
      of pregnant women in a population changing from high to lower consumption of milk
      and fish. DESIGN: Cross-sectional observational study. Urine samples were
      collected for measuring urinary iodine concentration (UIC) and creatinine, and
      blood samples for measuring serum thyroid-stimulating hormone (TSH). Frequency of
      consumption of selected food and beverages was obtained through a semi
      quantitative validated FFQ. The difference in the distribution of UIC, ratio of
      iodine to creatinine (I:Cr) and TSH between groups following recommendations on
      fish and dairy product intake or not (fish >=2 times/week as a main meal, diary
      products >=2 portions/d) was assessed. SETTING: Primary Health Care of the
      Capital Area, Reykjavik, Iceland. SUBJECTS: Randomly selected pregnant women (19
      43 years old, n 162). RESULTS: The median UIC was 180 MUg/l, I:Cr 173 MUg/g and
      TSH 1.5 mmol/l. Women who did not consume fish >=2 times/week and also did not
      consume dairy products in line with the recommended intake level of >=2
      portions/d had median UIC of 160 MUg/l (I:Cr 149 MUg/g) compared with 220 MUg/l
      (I:Cr 190 MUg/g) in the group following both the recommendations for fish and
      those for dairy products. Use of dietary supplements in the two groups was
      similar. CONCLUSIONS: Iodine status in the population studied was within the
      optimal range (150-249 MUg/d) defined by the WHO.

PMID- 22607719
TI  - Apparent triclabendazole-resistant human Fasciola hepatica infection, the
      Netherlands.

PMID- 22607720
TI  - Polycystic ovary syndrome resembling histopathological alterations in ovaries
      from prenatal androgenized female rats.
AB  - BACKGROUND: The polycystic ovary syndrome (PCOS) affects approximately 6-10% of
      women of reproductive age and is characterized by chronic anovulation and
      hyperandrogenism. However, a comprehensive understanding of the mechanisms that
      dictate androgen overproduction is lacking, which may account for inconsistencies
      between measures of androgen excess and clinical presentation in individual
      cases. METHODS: A rat model of PCOS was established by injecting
      dehydroepiandrosterone sulfoconjugate (DHEAS) into pregnant females. Rats were
      administered with DHEAS (60 mg/kg/d) subcutaneously (s.c.) for all 20 days of
      pregnancy (Group A), or for the first 10 days (Group B), or from day 11 to day 20
      (Group C). Controls were administered with injection oil (0.2 ml/day) s.c.
      throughout pregnancy (Group D). The litter rate, abortion rate, and offspring
      survival rate in each group were recorded. Serum androgen and estrogen were
      measured and the morphological features of the ovaries were examined by light and
      electron microscopy in the offspring of each group. RESULTS: We found that rats
      injected with DHEAS throughout pregnancy (group A) lost fertility. Rats injected
      with DHEAS during early pregnancy (group B) exhibited more serious aberrations in
      fertility than both Group C, in which rats were injected with DHEAS during late
      pregnancy (P < 0.05), and Group D (controls). There was a statistical difference
      of ovarian weight among female offspring in Group B, C and D (P < 0.01). By light
      and electron microscopy, a significant morphological difference among the female
      offspring in the three groups was observed. CONCLUSIONS: Our results indicate
      that androgen excess during pregnancy can decrease rat fertility. Excess androgen
      at the early stage of pregnancy causes high reproductive toxicity, leading to
      abnormality of ovarian morphology and functions in female offspring.

PMID- 22607721
TI  - Hepatoprotective effect of ethanolic extract of Trichosanthes lobata on
      paracetamol-induced liver toxicity in rats.
AB  - BACKGROUND: Trichosanthes lobata (family cucurbitaceae) is used to treat malarial
      fever and liver disorders. This study aims to investigate possible
      hepatoprotective activities of ethanolic extract of Trichosanthes lobata against
      paracetamol-induced hepatotoxicity. METHODS: Hepatotoxicity was induced in Wistar
      male rats by oral administration, 2 g/kg body weight on 7th day after the
      administration of ethanolic extract of Trichosanthes lobata and silymarin (100
      mg/kg). Ethanolic extract of Trichosanthes lobata was administered orally at
      doses of 200 mg/kg and 400 mg/kg body weight daily for 7 days. Several serum
      markers, aspartate transaminase, alanine transaminase, alkaline phosphatase,
      bilirubin, total protein was measured to assess the effect of the extract on
      paracetamol (acetaminophen)-induced hepatic damage. The study included
      histopathological examination of liver sections. RESULTS: Blood samples from rats
      treated with ethanolic extract of Trichosanthes lobata (200 mg/kg body weight and
      400 mg/kg body weight) had significant reductions in serum markers in paracetamol
      administered animals, indicating the effect of the extract in restoring the
      normal functional ability of hepatocytes. Silymarin (100 mg/kg, p.o.) was used as
      a reference drug. CONCLUSION: The ethanolic extract of Trichosanthes lobata
      exhibits protective effects against paracetamol-induced hepatotoxicity.

PMID- 22607722
TI  - Avian influenza a (H5N1) virus antibodies in poultry cullers, South Korea, 2003
      2004.
AB  - Transmission of influenza (H5N1) virus from birds to humans is a serious public
      health threat. In South Korea, serologic investigation among 2,512 poultry
      workers exposed during December 2003-March 2004 to poultry with confirmed or
      suspected influenza (H5N1) virus infection found antibodies in 9. Frequency of
      bird-to-human transmission was low.

PMID- 22607723
TI  - Sociodemographic determinants of early weaning: a Finnish birth cohort study in
      infants with human leucocyte antigen-conferred susceptibility to type 1 diabetes.
AB  - OBJECTIVE: To assess the most important sociodemographic determinants of age at
      introduction of complementary foods in infancy. DESIGN: A prospective birth
      cohort with increased risk of type 1 diabetes, recruited between 1996 and 2004.
      The families completed at home a follow-up form on the age at introduction of new
      foods and, for each clinic visit, a structured dietary questionnaire with 3 d
      food records. SETTING: Data from the Type 1 Diabetes Prediction and Prevention
      (DIPP) Project, Finland. SUBJECTS: A cohort of 5991 infants (77 % of those
      invited) belonging to the DIPP Nutrition Study. RESULTS: Sixty-three per cent of
      the infants were introduced to complementary foods, including infant formula,
      before the age of 4 months. The median age at introduction of infant formula was
      1.5 months (range 0-18 months) and that of the first other complementary food 3.5
      months (range 0.7-8 months). All sociodemographic and lifestyle factors studied
      were associated with the age at introduction of infant formula and/or first other
      complementary food. Female sex of the infant, being born in the southern region
      of Finland, living in a rural municipality, the presence of siblings, the mother
      or the father being a high-school graduate, high maternal professional education
      and maternal non-smoking during pregnancy predicted later introduction of
      complementary foods. CONCLUSIONS: Compliance was relatively poor with the current
      recommendations for the age of introducing complementary foods. Small-sized young
      families with less well-educated parents were most prone to introduce
      complementary foods early.

PMID- 22607725
TI  - Possibility of leishmaniasis transmission in Jura, France.

PMID- 22607724
TI  - Inducement of semitendinosus tendon regeneration to the pes anserinus after its
      harvest for anterior cruciate ligament reconstruction-A new inducer grafting
      technique.
AB  - PURPOSE: To investigate the usefulness of the "inducer grafting" technique for
      regeneration of the semitendinosus (ST) tendon after its harvest for anterior
      cruciate ligament (ACL) reconstruction. METHODS: Twenty knees of 20 patients
      (mean age at the time of surgery, 23.1 years) underwent ACL reconstruction with a
      double bundle autograft using the ST tendon (7 patients) and the ST + the
      gracilis (G) tendons (13 patients)."Inducer grafting" techniqueAfter harvesting
      the ST tendon, a passing pin with a loop thread is inserted along with the tendon
      stripper. The passing pin is pulled out from the medial thigh and the loop thread
      retained. As an inducer graft, the ST tendon branch is used. After the ACL graft
      has been secured, the inducer graft is sutured to the pes anserinus and the
      proximal end passed through by pulling the thread out. Then the inducer graft is
      placed within the tendon canal. The mean follow-up period was 15 months. The
      presence and morphology of the regenerated ST tendon were examined by MRI. And
      the isometric hamstring strength was examined at 45 degrees , 90 degrees  and 120
      degrees  of knee flexion. RESULTS: One month after the operation in all the
      patients, MRI demonstrated a low-intensity structure at the anatomical location
      of the ST, at the level of the superior pole of the patella and the joint line,
      apparently representing the regenerated ST tendon. Four months after the
      operation, the distal portion of the regenerated ST tendon had reached the pes
      anserinus in all patients. Twelve months after the operation, the regenerated ST
      tendon was hypertrophic in 19 of the 20 patients (95%). The isometric knee
      flexion torque of the ACL-reconstructed limb was significantly lower at 90
      degrees  and 120 degrees  compared with the contralateral limb. CONCLUSION: These
      results suggest that the "inducer grafting" technique is able to improve the
      regeneration rate of the harvested ST tendon and promote hypertrophy of the
      regenerated ST tendon, extending all the way to the pes anserinus. However, this
      technique couldn't improve the deficits in knee flexion torque after ACL
      reconstruction.

PMID- 22607726
TI  - Does access to a colorectal cancer screening website and/or a nurse-managed
      telephone help line provided to patients by their family physician increase fecal
      occult blood test uptake?: A pragmatic cluster randomized controlled trial study
      protocol.
AB  - BACKGROUND: Fecal occult blood test screening in Canada is sub-optimal. Family
      physicians play a central role in screening and are limited by the time
      constraints of clinical practice. Patients face multiple barriers that further
      reduce completion rates. Tools that support family physicians in providing their
      patients with colorectal cancer information and that support uptake may prove
      useful. The primary objective of the study is to evaluate the efficacy of a
      patient decision aid (nurse-managed telephone support line and/or colorectal
      cancer screening website) distributed by community-based family physicians, in
      improving colorectal cancer screening rates. Secondary objectives include
      evaluation of (dis)incentives to patient FOBT uptake and internet use among 50 to
      74 year old males and females for health-related questions. Challenges faced by
      family physicians in engaging in collaborative partnerships with primary
      healthcare researchers will be documented. METHODS/DESIGN: A pragmatic, two-arm,
      randomized cluster controlled trial conducted in 22 community-based family
      practice clinics (36 clusters) with 76 fee-for-service family physicians in
      Winnipeg, Manitoba, Canada. Each physician will enroll 30 patients attending
      their periodic health examination and at average risk for colorectal cancer. All
      physicians will follow their standard clinical practice for screening.
      Intervention group physicians will provide a fridge magnet to each patient that
      contains information facilitating access to the study-specific colorectal cancer
      screening decision aids (telephone help-line and website). The primary endpoint
      is patient fecal occult blood test completion rate after four months (intention
      to treat model). Multi-level analysis will include clinic, physician and patient
      level variables. Patient Personal Health Identification Numbers will be collected
      from those providing consent to facilitate analysis of repeat screening behavior.
      Secondary outcome data will be obtained through the Clinic Characterization Form,
      Patient Tracking Form, In-Clinic Patient Survey, Post-Study Follow-Up Patient
      Survey, and Family Physician Survey. Study protocol approved by The University of
      Manitoba Health Research Ethics Board. DISCUSSION: The study intervention has the
      potential to increase patient fecal occult blood test uptake, decrease colorectal
      cancer mortality and morbidity, and improve the health of Manitobans. If
      utilization of the website and/or telephone support line result in clinically
      significant increases in colorectal cancer screening uptake, changes in screening
      at the policy- and system-level may be warranted. TRIAL REGISTRATION: Clinical
      trials.gov identifier NCT01026753.

PMID- 22607727
TI  - From networks of protein interactions to networks of functional dependencies.
AB  - BACKGROUND: As protein-protein interactions connect proteins that participate in
      either the same or different functions, networks of interacting and functionally
      annotated proteins can be converted into process graphs of inter-dependent
      function nodes (each node corresponding to interacting proteins with the same
      functional annotation). However, as proteins have multiple annotations, the
      process graph is non-redundant, if only proteins participating directly in a
      given function are included in the related function node. RESULTS: Reasoning that
      topological features (e.g., clusters of highly inter-connected proteins) might
      help approaching structured and non-redundant understanding of molecular
      function, an algorithm was developed that prioritizes inclusion of proteins into
      the function nodes that best overlap protein clusters. Specifically, the
      algorithm identifies function nodes (and their mutual relations), based on the
      topological analysis of a protein interaction network, which can be related to
      various biological domains, such as cellular components (e.g., peroxisome and
      cellular bud) or biological processes (e.g., cell budding) of the model organism
      S. cerevisiae. CONCLUSIONS: The method we have described allows converting a
      protein interaction network into a non-redundant process graph of inter-dependent
      function nodes. The examples we have described show that the resulting graph
      allows researchers to formulate testable hypotheses about dependencies among
      functions and the underlying mechanisms.

PMID- 22607728
TI  - Bartonella vinsonii subsp. arupensis in humans, Thailand.
AB  - We identified Bartonella vinsonii subsp. arupensis in pre-enriched blood of 4
      patients from Thailand. Nucleotide sequences for transfer-messenger RNA gene,
      citrate synthase gene, and the 16S-23S rRNA internal transcribed spacer were
      identical or closely related to those for the strain that has been considered
      pathogenic since initially isolated from a human in Wyoming, USA.

PMID- 22607729
TI  - Health behaviours and health-care utilization in Canadian schoolchildren.
AB  - OBJECTIVE: Poor nutritional habits and physical inactivity are two health
      behaviours believed to be linked with increasing rates of overweight and obesity
      in children. The objective of the present study was to determine whether children
      who reported healthier behaviours, specifically in relation to nutrition and
      physical activity, also had lower health-care utilization. DESIGN: Population
      based cross-sectional study, linking survey data from the 2003 Children's
      Lifestyle and School Performance Study (CLASS) with Nova Scotia administrative
      health data. Health-care utilization was defined as both (i) the total physician
      costs and (ii) the number of physician visits, for each child from 2001 to 2006.
      Exposures were two indices of healthy eating, the Diet Quality Index and the
      Healthy Eating Index, and self-reported physical activity and screen time
      behaviours. SETTING: Elementary schools in the Canadian province of Nova Scotia.
      SUBJECTS: Grade 5 students and their parents; of the 5200 students who
      participated in CLASS and completed surveys, 4380 (84 %) could be linked with
      information in the administrative data sets. RESULTS: The study found a
      relationship between both indices of healthy eating and a borderline significant
      trend towards lower health-care utilization in this population sample of
      children. No statistically significant relationships were seen for physical
      activity or screen time. CONCLUSIONS: Both measures of diet quality produced
      similar results. The study suggests that healthy eating habits established in
      childhood may be associated with lower health-care utilization, although further
      research over a longer time frame is needed to demonstrate statistical
      significance.

PMID- 22607730
TI  - Definitive radiotherapy for early stage glottic cancer by 6 MV photons.
AB  - PURPOSE: To evaluate the clinical outcome of early glottic cancer (GC) treated by
      primary radiotherapy (RT) with 6 MV photons. METHODS AND MATERIALS: We
      retrospectively reviewed the medical records of 695 consecutive patients with
      T1N0 and T2N0 GC treated between 1983 and 2005 by RT in our institution. Clinical
      outcome in terms of local control (LC), overall survival (OS) and cause- specific
      survival (CSS) rate were evaluated. RESULTS: The median follow-up time was 10.5
      years. The 10-year actuarial LC rates were as follows: T1A, 91%; T1B, 87%; T2,
      77%. The 10-year OS were as follows: T1, 74.2%; T2, 70.7%. The 10-year CSS were
      as follows: T1, 97.7%; T2, 97.1%.Poorly differentiated histology and tumor
      biologically effective dose<65 Gy15 were adverse factors in both LC of T1 and T2
      disease. Involvement of anterior commissure was an adverse factor in both LC and
      CSS of T1 disease. Subglottic extension was associated with poor LC in T2 disease
      whereas hemoglobin <13.0 was associated with poor LC and CSS of T2 disease.
      CONCLUSION: Primary RT remains an option among the various standard treatments
      for early GC. Clinical treatment outcome by 6MV photons is similar and comparable
      to historic data of Cobalt-60 and 2 MV photons.

PMID- 22607731
TI  - Etymologia: prion.

PMID- 22607733
TI  - Immunodeficiency-associated vaccine-derived poliovirus type 3 in infant, South
      Africa, 2011.
AB  - Patients with primary immunodeficiency are prone to persistently excrete Sabin
      like virus after administration of live-attenuated oral polio vaccine and have an
      increased risk for vaccine-derived paralytic polio. We report a case of type 3
      immunodeficiency-associated vaccine-derived poliovirus in a child in South Africa
      who was born with X-linked immunodeficiency syndrome.

PMID- 22607732
TI  - Modeling of human factor Va inactivation by activated protein C.
AB  - BACKGROUND: Because understanding of the inventory, connectivity and dynamics of
      the components characterizing the process of coagulation is relatively mature, it
      has become an attractive target for physiochemical modeling. Such models can
      potentially improve the design of therapeutics. The prothrombinase complex
      (composed of the protease factor (F)Xa and its cofactor FVa) plays a central role
      in this network as the main producer of thrombin, which catalyses both the
      activation of platelets and the conversion of fibrinogen to fibrin, the main
      substances of a clot. A key negative feedback loop that prevents clot propagation
      beyond the site of injury is the thrombin-dependent generation of activated
      protein C (APC), an enzyme that inactivates FVa, thus neutralizing the
      prothrombinase complex. APC inactivation of FVa is complex, involving the
      production of partially active intermediates and "protection" of FVa from APC by
      both FXa and prothrombin. An empirically validated mathematical model of this
      process would be useful in advancing the predictive capacity of comprehensive
      models of coagulation. RESULTS: A model of human APC inactivation of
      prothrombinase was constructed in a stepwise fashion by analyzing time courses of
      FVa inactivation in empirical reaction systems with increasing number of
      interacting components and generating corresponding model constructs of each
      reaction system. Reaction mechanisms, rate constants and equilibrium constants
      informing these model constructs were initially derived from various research
      groups reporting on APC inactivation of FVa in isolation, or in the presence of
      FXa or prothrombin. Model predictions were assessed against empirical data
      measuring the appearance and disappearance of multiple FVa degradation
      intermediates as well as prothrombinase activity changes, with plasma proteins
      derived from multiple preparations. Our work integrates previously published
      findings and through the cooperative analysis of in vitro experiments and
      mathematical constructs we are able to produce a final validated model that
      includes 24 chemical reactions and interactions with 14 unique rate constants
      which describe the flux in concentrations of 24 species. CONCLUSION: This study
      highlights the complexity of the inactivation process and provides a module of
      equations describing the Protein C pathway that can be integrated into existing
      comprehensive mathematical models describing tissue factor initiated coagulation.

PMID- 22607734
TI  - Dopamine D4 receptor gene variation is associated with context-dependent
      attention for emotion stimuli.
AB  - Dopamine D(4) receptor (DRD4) gene variation has been associated with biased
      attention for contextually relevant information (e.g. images of cigarettes among
      smokers). No research has examined whether DRD4 variation is associated with
      biased attention for contextually cued emotion stimuli, an important putative
      intermediate phenotype for a number of pathologies (e.g. depression and anxiety).
      We conducted two studies examining the relationship between the DRD4 variable
      number tandem repeats polymorphism and attention bias for facial expressions of
      emotion following a mood-state manipulation in healthy young adult samples. Study
      1 demonstrated that long (i.e. seven or greater tandem repeats) DRD4 allele
      carriers vs. short DRD4 homozygotes had increased attention for sad facial
      stimuli, but only after a sad mood provocation. Study 2 demonstrated an
      association between the long DRD4 allele and attention for negative stimuli (sad
      and fear expressions) following a sad mood provocation. These studies are the
      first to demonstrate an association between the long DRD4 allele and biased
      attention for contextually cued emotion stimuli, an important cognitive mechanism
      thought to increase risk for affective psychopathology. Implications of these
      studies for vulnerability and plasticity models of psychiatric genetics are
      discussed.

PMID- 22607735
TI  - Branchial cysts within the parotid salivary gland.
AB  - Cystic lesions within the parotid gland are uncommon and clinically they are
      frequently misdiagnosed as tumours. Many theories have been proposed as to their
      embryological origin. A 20-year retrospective review was undertaken of all
      pathological codes (SNOMED) of all of patients presenting with any parotid
      lesions requiring surgery. After analysis seven subjects were found to have
      histopathologically proven parotid branchial cysts in the absence of HIV
      infection and those patients are the aim of this review. Four of the most common
      embryological theories are also discussed with regard to these cases, as are
      their management.

PMID- 22607736
TI  - Hormone levels and cognitive function in postmenopausal midlife women.
AB  - Gonadal hormones may influence cognitive function. Postmenopausal midlife women
      in the population-based Melbourne Women's Midlife Health Project cohort were
      administered a comprehensive battery of neuropsychological tests on two occasions
      2 years apart. Participants (n = 148, mean age 60 years) had undergone natural
      menopause and were not using hormone therapy. Estrone, total and free estradiol,
      and total and free testosterone levels were measured at time of the first
      testing. Principal-component analysis identified four cognitive factors. In
      multiple linear regression analyses, better semantic memory performance was
      associated with higher total (p = 0.02) and free (p = 0.03) estradiol levels and
      a lower ratio of testosterone to estradiol (p = 0.007). There were trends for
      associations between better verbal episodic memory and lower total testosterone
      (p = 0.08) and lower testosterone/estradiol ratio (p = 0.06). Lower free
      testosterone levels were associated with greater 2-year improvement on verbal
      episodic memory (p = 0.04); higher testosterone/estradiol predicted greater
      semantic memory improvement (p = 0.03). In postmenopausal midlife women,
      endogenous estradiol and testosterone levels and the testosterone/estradiol ratio
      are associated with semantic memory and verbal episodic memory abilities.

PMID- 22607737
TI  - Wing flap reconstruction for large defects of the lower lip.
AB  - Full-thickness lower lip defects most often occur due to tumour resection or
      injury. Because the lower lip is important for both eating and speaking,
      reconstruction of the region must restore the structure and function of the
      tissue. Here, we describe a new procedure to reconstruct the lower lip, using a
      'wing flap': a mental V-Y rotational advancement flap that contains the mental
      nerve. This flap can preserve the sensory innervation of the lower lip, and it
      allows effective reconstruction of the muscle sling. We have employed this method
      twice and have obtained good aesthetic and functional outcomes. No special
      technique is required to reconstruct the lip using this flap, and it yields a
      satisfactory outcome. Thus, we recommend it as an effective method for
      reconstruction in wide lower lip defects.

PMID- 22607738
TI  - Protocolisation and 'end' point of free-flap salvage.

PMID- 22607739
TI  - Gender and race are significant determinants of students' food choices on a
      college campus.
AB  - OBJECTIVE: To examine the roles of gender and race in students' determinants of
      food choices on a college campus. METHODS: A total of 405 college students
      participated in a survey entitled "Campus Food: You Tell Us!" Chi-square and
      logistic regression were used to examine associations between demographics and
      food choice determinants. RESULTS: Gender and race appeared to play a significant
      role in determinants of students' food dislikes. Males were significantly more
      likely to choose cost, taste, and poor quality over poor nutrition as
      determinants. White students were significantly less likely to choose cost,
      inconvenience, and taste over poor nutrition than students of other races. Gender
      was also a significant factor associated with student preferences for campus
      dining location and determinants of unhealthful food. CONCLUSIONS AND
      IMPLICATIONS: Future marketing may be more effective if tailored to gender and
      race. Nutrition educators should consider addressing taste and convenience when
      attempting to influence students' food choices.

PMID- 22607740
TI  - Outcomes of laparoscopic colon cancer surgery in a population-based cohort in
      British Columbia: are they as good as the clinical trials?
AB  - BACKGROUND: Randomized controlled trials have shown equivalent outcomes for
      laparoscopic-assisted colectomy (LAC) and open colectomy (OC) when performed by
      well-trained surgeons experienced in both techniques. Our goal was to evaluate
      the outcomes of LAC at a population level. METHODS: Using the prospectively
      collected Gastrointestinal Cancer Outcomes Unit database from the British
      Columbia Cancer Agency, short- and long-term outcomes in patients with colon
      cancer treated with LAC and OC were compared from 2003 to 2008 inclusive.
      RESULTS: There was a statistically significant increase in the proportion of LAC
      from 2003 to 2008 (P < .001). LAC was more likely to be performed in the elective
      setting (P < .001) and for smaller tumors (P < .001). A similar proportion of
      patients had a minimum of 12 lymph nodes identified by pathology (58% vs 60%, P =
      not significant). Disease-free survival was similar for the 2 groups after
      adjusting for stage, emergency presentation, and adjuvant chemotherapy. There was
      no difference in overall survival. CONCLUSIONS: The introduction of LAC for colon
      cancer in British Columbia outside of optimized clinical trial conditions appears
      to be effective and safe.

PMID- 22607741
TI  - Transversus abdominis muscle release: a novel approach to posterior component
      separation during complex abdominal wall reconstruction.
AB  - BACKGROUND: Several modifications of the classic retromuscular Stoppa technique
      to facilitate dissection beyond the lateral border of the rectus sheath recently
      were reported. We describe a novel technique of transversus abdominis muscle
      release (TAR) for posterior component separation during major abdominal wall
      reconstructions. METHODS: Retrospective review of consecutive patients undergoing
      TAR. Briefly, the retromuscular space is developed laterally to the edge of the
      rectus sheath. The posterior rectus sheath is incised 0.5-1 cm underlying medial
      to the linea semilunaris to expose the medial edge of the transversus abdominis
      muscle. The muscle then is divided, allowing entrance to the space anterior to
      the transversalis fascia. The posterior rectus fascia then is advanced medially.
      The mesh is placed as a sublay and the linea alba is restored ventral to the
      mesh. RESULTS: Between December 2006 and December 2009, we have used this
      technique successfully in 42 patients with massive ventral defects. Thirty-two
      (76.2%) patients had recurrent hernias. The average mesh size used was 1,201 +/-
      820 cm(2) (range, 600-2,700). Ten (23.8%) patients developed various wound
      complications requiring reoperation/debridement in 3 patients. At a median follow
      up period of 26.1 months, there have been 2 (4.7%) recurrences. CONCLUSIONS: Our
      novel technique for posterior component separation was associated with a low
      perioperative morbidity and a low recurrence rate. Overall, transversus abdominis
      muscle release may be an important addition to the armamentarium of surgeons
      undertaking major abdominal wall reconstructions.

PMID- 22607742
TI  - A specialized ODE integrator for the efficient computation of parameter
      sensitivities.
AB  - BACKGROUND: Dynamic mathematical models in the form of systems of ordinary
      differential equations (ODEs) play an important role in systems biology. For any
      sufficiently complex model, the speed and accuracy of solving the ODEs by
      numerical integration is critical. This applies especially to systems
      identification problems where the parameter sensitivities must be integrated
      alongside the system variables. Although several very good general purpose ODE
      solvers exist, few of them compute the parameter sensitivities automatically.
      RESULTS: We present a novel integration algorithm that is based on second
      derivatives and contains other unique features such as improved error estimates.
      These features allow the integrator to take larger time steps than other methods.
      In practical applications, i.e. systems biology models of different sizes and
      behaviors, the method competes well with established integrators in solving the
      system equations, and it outperforms them significantly when local parameter
      sensitivities are evaluated. For ease-of-use, the solver is embedded in a
      framework that automatically generates the integrator input from an SBML
      description of the system of interest. CONCLUSIONS: For future applications,
      comparatively 'cheap' parameter sensitivities will enable advances in solving
      large, otherwise computationally expensive parameter estimation and optimization
      problems. More generally, we argue that substantially better computational
      performance can be achieved by exploiting characteristics specific to the problem
      domain; elements of our methods such as the error estimation could find broader
      use in other, more general numerical algorithms.

PMID- 22607743
TI  - Rickettsia parkeri infection in domestic dogs, Southern Louisiana, USA, 2011.
AB  - The association between companion animals and tick-borne rickettsial disease has
      long been recognized and can be essential to the emergence of rickettsioses. We
      tested whole blood from dogs in temporary shelters by using PCR for rickettsial
      infections. Of 93 dogs, 12 (13%) were positive for Rickettsia parkeri, an
      emerging tick-borne rickettsiosis.

PMID- 22607744
TI  - Interaction and nanotoxic effect of TiO2 nanoparticle on fibrinogen by multi
      spectroscopic method.
AB  - Toxicological effects of nanoparticles (NPs) are still poorly documented while
      there are great demands for industrial applications and daily life. The aim of
      this study is to evaluate the influence of physicochemical characteristics on
      TiO2 NP toxicological effects toward protein. In order to better understand the
      physicochemical basis of the toxic of NP in industrial applications and under
      conditions of environmental exposure, we performed an array of photophysical
      measurements to quantify the interaction of TiO2 NP with protein. Fluorescence
      quenching, circular dichroism, dynamic light scattering and transmission electron
      microscopy measurements were performed on TiO2 NP having a diameter range from 10
      to 35 nm in the performance of protein. We find that the TiO2 NP strongly
      associates with protein where the binding constant, as well as the degree of
      cooperativity of particle-protein binding, depends on particle size. We also find
      tentative evidence that the protein undergoes conformational change upon
      association with the NP. These results indicate that exposure to TiO2 NP may have
      an unfavorable effect on human health by inactivating functional proteins.

PMID- 22607745
TI  - Young-onset multiple system atrophy.
AB  - BACKGROUND: Multiple system atrophy (MSA) rarely begins before the age of 40 and
      detailed descriptions of young-onset MSA are lacking. METHODS: Among 455 patients
      included in our MSA cohort, four developed disease before the age of 40. We
      reviewed the medical records of these patients. RESULTS: Case 1 and 2 presented
      with cerebellar symptoms. Case 1 had clinical features and a course typical of
      MSA. Case 2 had a rapid course and died 3 years after onset. Case 3 and Case 4
      presented with levodopa-responsive parkinsonism. Both developed motor
      fluctuations and peak-dose limb dyskinesias. Subthalamic deep brain stimulation
      (DBS) resulted in some improvements in motor symptoms, but they became totally
      dependent within a few years. DISCUSSION: Young-onset MSA is rare but does exist.
      Young-onset MSA with predominant parkinsonism may closely resemble Parkinson
      disease at onset and is likely to develop motor complications. Attention should
      be given to the possibility of young-onset MSA in selecting DBS candidates.

PMID- 22607747
TI  - IVF policy and global/local politics: the making of multiple-embryo transfer
      regulation in Taiwan.
AB  - This paper analyzes the regulatory trajectory of multiple-embryo transfer in in
      vitro fertilization (IVF) in Taiwan. Taking a latecomer to policy-making as the
      case, it argues the importance of conceptualizing the global/local dynamics in
      policy-making for assisted reproductive technology (ART). The conceptual
      framework is built upon recent literature on standardization, science policy, and
      global assemblage. I propose three interrelated features that reveal the "global
      in the local": (1) the power relationships among stakeholders, (2) the selected
      global form that involved actors drew upon, and (3) the re-contextualized
      assemblage made of local networks. Data included archives, interviews, and
      participant observation. In different historical periods the specific
      stakeholders selected different preferred global forms for Taiwan, such as
      Britain's code of ethics in the 1990s, the American guideline in the early 2000s,
      and the European trend in the mid-2000s. The global is heterogeneous. The failure
      to transfer the British regulation, the revision of the American guideline by
      adding one more embryo than it specified, and the gap between the cited European
      trend and the "no more than four" in Taiwan's 2007 Human Reproduction Law all
      show that the local network further transforms the selected global form,
      confining it to rhetoric only or tailoring it to local needs. Overall, Taiwanese
      practitioners successfully maintained their medical autonomy to build a 'flexible
      standardization'. Multiple pregnancy remains the most common health risk of IVF
      in Taiwan.

PMID- 22607746
TI  - Ethnic disparities in adolescent body mass index in the United States: the role
      of parental socioeconomic status and economic contextual factors.
AB  - This paper examined the importance of household and economic contextual factors
      as determinants of ethnic disparities in adolescent body mass index (BMI).
      Individual-level data from the National Longitudinal Survey of Youth 1997 for the
      years 1997 through 2000 were combined with economic contextual data on food
      prices, outlet density and median household income. The Oaxaca-Blinder
      decomposition method was used to examine the factors that could help explain
      ethnic disparities in BMI. Ethnic differences in household demographic, parental
      socioeconomic status (SES), and economic contextual factors explained the
      majority of the male black-white (63%), male Hispanic-white (78%) and female
      Hispanic-white (62%) BMI gaps but less than one-half of the female black-white
      BMI gap (44%). We found that adding the economic contextual factors increased the
      explained portion of the ethnic BMI gap for both female and male adolescents: the
      economic contextual factors explained 28% and 38% of the black-white and Hispanic
      white BMI gaps for males and 13% and 8% of the black-white and Hispanic-white BMI
      gaps for females, respectively. Parental SES was more important in explaining the
      Hispanic-white BMI gap than the black-white BMI gap for both genders, whereas
      neighborhood economic contextual factors were more important in explaining the
      male BMI gap than the female BMI gap for both black-white and Hispanic-white
      ethnic disparities. A significantly large portion of the ethnic BMI gap, however,
      remained unexplained between black and white female adolescents.

PMID- 22607748
TI  - Caregivers' responses to an intervention to improve young child feeding behaviors
      in rural Bangladesh: a mixed method study of the facilitators and barriers to
      change.
AB  - Behavior change communications regarding child feeding have met with mixed
      success. The present study analyzes responses of 34 Bangladeshi caregivers seven
      months after they received a responsive feeding intervention. The intervention
      communicated and demonstrated five feeding interactions: hand-washing, self
      feeding, verbal responsivity, managing refusals non-forcefully, and dietary
      diversity. Seventeen caregivers who adopted key behaviors addressed by the
      intervention and 17 who did not were compared in terms of socio-demographic
      variables, but more importantly in terms of their recall of the messages, their
      reported practice, and reported facilitators and barriers. Both those who changed
      and those who did not reported similar facilitators and barriers to practicing
      the new behaviors; there was also no difference in recall or in socio-demographic
      variables. Key themes identified through a constant comparative analysis helped
      to focus on common features of the lives of caregivers that made it easy or
      difficult to perform the practices. Some of these were household constraints such
      as poverty, shortage of time in which to complete chores, and avoiding waste and
      messiness; others related to the child's demands. Many caregivers misinterpreted
      instructions about talking to one's child in response to signals, as opposed to
      more common forms of supervision. Facilitators such as the child's evident
      pleasure and the caregiver's satisfaction did not always outweigh the barriers.
      Recommendations for improving interventions include helping caregivers solve
      problems tied to barriers and including more family members in the intervention.

PMID- 22607749
TI  - ARM: axillary reverse mapping - the need for selection of patients.
AB  - BACKGROUND: Axillary reverse mapping (ARM) is a technique that discerns axillary
      lymphatic drainage of the arm from the breast. This study was performed to
      evaluate both the feasibility of this technique and the proportion of metastatic
      involvement of ARM-nodes. PATIENTS AND METHODS: Patients with invasive breast
      cancer and an indication for axillary lymph node dissection (ALND) were enrolled
      in the study: patients with a tumor-positive sentinel lymph node (SLN(+)-group)
      and patients who had axillary metastases proven by preoperative cytology (CP-N(+)
      group) were distinguished. ARM was performed in all patients by injecting blue
      dye. During surgery ARM-nodes were identified and removed first, followed by
      ALND. RESULTS: Between October 2009 and June 2011 93 patients underwent ARM.
      There were 43 patients in the SLN(+)-group and 50 patients in the CP-N(+)-group.
      No significant differences in visualization rate of ARM-nodes between the groups
      (86 vs 94% respectively, P = 0.196) were identified. In the SLN(+)-group none of
      the ARM-nodes contained metastases versus 11 patients (22%) in the CP-N(+)-group
      (P = 0.001). Patients receiving neoadjuvant systemic therapy had a significantly
      lower risk of additional axillary lymph node metastases (24.6 vs 44.4%, P =
      0.046). DISCUSSION: The ARM procedure is technically feasible with a high
      visualization rate. The proportion of patients with metastases in the ARM-nodes
      was significantly higher in patients with proven axillary metastases than in
      patients with a positive SLN. Patients with SLN metastases appear to be good
      candidates for the ARM technique and possibly also patients with proven axillary
      metastases receiving neoadjuvant chemotherapy.

PMID- 22607750
TI  - Structural and computational enzymology: bringing experiments and computations
      together.
AB  - In this introductory chapter, we present how the experimental and computational
      strategies in enzyme research are developed and how they complement each other to
      provide better insights for understanding enzyme structures and mechanisms.

PMID- 22607751
TI  - Structural and functional analysis of proteins by high-speed atomic force
      microscopy.
AB  - Proteins are dynamic in nature, work at the single-molecule level, and facilitate
      several biological functions. The structure of a protein is closely associated
      with its function; thus, a large number of structural analyses of proteins were
      performed using techniques such as X-ray crystallography and NMR. Although these
      methods provide structural information, they often fail because of difficulties
      in crystallizing the proteins that are complexed with other biomolecules.
      Moreover, these techniques do not allow the observation of structural changes in
      the active form of the molecule. Single-molecule fluorescence techniques have
      been used for the direct observation of protein functions; however, they only
      reveal the dynamics of individual fluorescent spots, rather than the structural
      changes that occur over the entire protein. The recent development of high-speed
      atomic force microscopy (HS-AFM) overcame this problem and allowed the
      observation of the structural dynamics of proteins and other biomacromolecules
      directly and in real time. In this chapter, we describe the HS-AFM analysis of
      the dynamic molecular processes in photoactivated bacteriorhodopsin, membrane
      mediated protein-protein interactions, ATP-induced conformational changes in
      purinergic receptors, the two-dimensional crystal structure of streptavidin, the
      nature of FtsZ polymers, the role of ClpX in the regulation of FtsZ polymer
      dynamics, the function of restriction enzymes, the action of motor proteins, the
      movement of TrCel7A on crystalline cellulose substrates, and the antimicrobial
      peptide activity on individual bacterial cells.

PMID- 22607752
TI  - Reaction intermediates discovered in crystal structures of enzymes.
AB  - Crystal structures of enzymes have provided valuable information for the reaction
      mechanisms. Structures of the enzyme complex with different reaction
      intermediates are particularly valuable. In several cases, these structures of
      intermediates were discovered accidently, presumably by trapping in the crystal
      during freezing prior to X-ray data collection. High to atomic resolution
      structures reveal the detailed geometry of the reaction intermediate and its
      interactions within the enzyme active site. In other cases, the protein can be
      crystallized with its substrate, including examples of protease precursors that
      represent their own substrates. Examples are described of an FAD-dependent
      dehydrogenase, HIV protease and caspases, where the structures provide snapshots
      of steps in the reaction and the conformational changes occurring during the
      reaction. Complementary techniques such as computational chemistry, neutron
      crystallography, Laue crystallography, and time-resolved spectroscopy can give a
      more complete picture of the reaction.

PMID- 22607753
TI  - Structural, functional, and mutagenesis studies of UDP-glycosyltransferases.
AB  - The biosynthesis of the complex carbohydrates that govern many cellular functions
      requires the action of a diverse range of selective glycosyltransferases (GTs).
      Uridine diphosphate sugar-utilizing GTs (UGTs) account for the majority of
      characterized GTs. GTs have been classified into families (currently 92) based on
      amino-acid sequence similarity. However, as amino-acid sequence similarity cannot
      reliable predict catalytic mechanism, GTs have also been grouped into four clans
      based on catalytic mechanism and structural fold. GTs catalyze glycosidic bond
      formation with two possible stereochemical outcomes: inversion or retention of
      anomeric configuration. All UGTs also belong to one of two distinct structural
      folds, GT-A and GT-B. UGTs have conserved residues that are associated with
      nucleotide diphosphate sugar recognition and acceptor recognition. UGT
      diversification has been performed using in vitro DNA recombination, domain
      swapping, and random mutagenesis.

PMID- 22607754
TI  - Vipoxin and its components: structure-function relationship.
AB  - The neurotoxin Vipoxin has been of growing research interest since the time of
      its isolation from the venom of the Bulgarian viper Vipera ammodytes
      meridionalis. Vipoxin is a heterodimeric postsynaptic ionic complex composed of
      two protein subunits-a basic and strongly toxic His48 secretory phospholipase
      A(2) (sPLA(2)) enzyme and an acidic, enzymatically inactive and nontoxic
      component, originally named Inhibitor. When separated, sPLA(2) enzyme loses its
      toxicity in 3-4 days and catalytic activity in 2 weeks. After the establishment
      of the high degree of sequence homology (62%) and crystal structure of the
      subunits, Vipoxin was served as an example of molecular evolution of a toxic but
      unstable sPLA(2) into an inhibitor subunit which stabilizes the enzyme and
      preserves its pharmacological activity. Beginning our research on Vipoxin,
      intrigued by the unique relationship-structure-function and based on the previous
      experience, we were more than surprised to establish the lack of so-called
      inhibitory function of the acidic subunit on the toxicity and catalytic activity
      of basic sPLA(2). On the contrary, the acidic subunit activated the sPLA(2)
      enzyme in vitro. Our studies undoubtedly proved that is more correctly to present
      Vipoxin as a heterodimeric complex composed of one basic catalytic subunit and
      one acidic regulatory subunit. Their interaction in a common quaternary protein
      structure is more than a noncovalent association between the two subunits. It
      allows pharmacological sites to be targeted and biological functions to be
      potentiated. We attempt to present the previous studies and new findings on
      Vipoxin and its components.

PMID- 22607755
TI  - Experimental and theoretical studies of enzyme-catalyzed hydrogen-transfer
      reactions.
AB  - The mechanisms of enzyme-catalyzed reactions are medicinally important and
      present a fascinating intellectual challenge. Many experimental and theoretical
      techniques can shed light on these mechanisms, and here, we shall focus on the
      utility of kinetic isotope effects (KIEs) to study enzymatic reactions that
      involve hydrogen transfers. We will provide a short background on the prevailing
      models to interpret KIEs and then present more detailed reviews of two model
      enzymes: alcohol dehydrogenase and thymidylate synthase. These two examples
      provide a context to describe the types of experiments and theoretical
      calculations that drive this field forward and the kind of information each can
      furnish. We emphasize the importance of cooperation between experimentalists and
      theoreticians to continue the progress toward a comprehensive theory of enzyme
      catalysis.

PMID- 22607756
TI  - Protein flexibility and enzymatic catalysis.
AB  - The dynamic nature of protein structures has been recognized, established, and
      accepted as an intrinsic fundamental property with major consequences to their
      function. Nowadays, proteins are considered as networks of continuous motions,
      which reflect local flexibility and a propensity for global structural
      plasticity. Protein-protein and protein-small ligand interactions, signal
      transduction and assembly of macromolecular machines, allosteric regulation and
      thermal enzymatic adaptation are processes which require structural flexibility.
      In general, enzymes represent an attractive class among proteins in the study of
      protein flexibility and they can be used as model systems for understanding the
      implications of protein fluctuations to biological function. Flexibility of the
      active site is considered as a requirement for reduction of free energy barrier
      and acceleration of the enzymatic reaction while there is growing evidence which
      concerns the connection between flexibility and substrate turnover rate.
      Moreover, the role of conformational flexibility has been well established in
      connection with the accessibility of the active site, the binding of substrates
      and ligands, and release of products, stabilization and trapping of
      intermediates, orientation of the substrate into the binding cleft, adjustment of
      the reaction environment, etc.

PMID- 22607757
TI  - Molecular modeling of inhibitors of human DNA methyltransferase with a crystal
      structure: discovery of a novel DNMT1 inhibitor.
AB  - DNA methyltransferases (DNMTs) are promising epigenetic targets for the
      development of novel anticancer drugs and other diseases. Molecular modeling and
      experimental approaches are being used to identify and develop inhibitors of
      human DNMTs. Most of the computational efforts conducted so far with DNMT1 employ
      homology models of the enzyme. Recently, a crystallographic structure of the
      methyltransferase domain of human DNMT1 bound to unmethylated DNA was published.
      Following on our previous computational and experimental studies with DNMTs, we
      herein present molecular dynamics of the crystal structure of human DNMT1.
      Docking studies of established DNMT1 inhibitors with the crystal structure gave
      rise to a structure-based pharmacophore model that suggests key interactions of
      the inhibitors with the catalytic binding site. Results had a good agreement with
      the docking and pharmacophore models previously developed using a homology model
      of the catalytic domain of DNMT1. The docking protocol was able to distinguish
      active DNMT1 inhibitors from, for example, experimentally known inactive DNMT1
      inhibitors. As part of our efforts to identify novel inhibitors of DNMT1, we
      conducted the experimental characterization of aurintricarboxylic acid (ATA) that
      in preliminary docking studies showed promising activity. ATA had a submicromolar
      inhibition (IC(50)=0.68 MUM) against DNMT1. ATA was also evaluated for Dnmt3a
      inhibition showing an IC(50)=1.4 MUM. This chapter illustrates the synergy from
      integrating molecular modeling and experimental methods to further advance the
      discovery of novel candidates for epigenetic therapies.

PMID- 22607758
TI  - In silico strategies toward enzyme function and dynamics.
AB  - Enzymes are outstanding biocatalysts involved in a plethora of chemical reactions
      occurring in the cell. Despite their incommensurable importance, a comprehensive
      understanding of enzyme catalysis is still missing. This task becomes more
      laborious given the unavoidability of including the inherent dynamic nature of
      enzymes into that description. As such, it is essential to ascertain the nature
      and contribution of enzyme conformational changes to catalysis and to evaluate
      the adequacy of the proposal associating protein internal motions to the rate
      enhancement achieved. Dynamic events in enzymes span a wide range of time- and
      length-scales which have led to a surge in multiscale methodologies targeting
      enzyme function and dynamics. Computational strategies assume a preponderant role
      in such studies by allowing the atomic detail investigation of the fundamental
      mechanisms of enzyme catalysis thus surpassing what is achievable through
      experiments. While high-accuracy quantum mechanical methods are indicated to
      uncover the details of the chemical reaction occurring at the active site,
      molecular mechanical force fields and molecular dynamics approaches provide
      powerful means to access the conformational energy landscape accessible to
      enzymes. This review outlines some of the most important in silico methodologies
      in this area, highlighting examples of problems tackled and the insights
      obtained.

PMID- 22607759
TI  - Dynamic simulations as a complement to experimental studies of enzyme mechanisms.
AB  - Dynamic simulations are a useful means of studying certain aspects of enzyme
      reaction mechanisms that cannot be understood easily through current experimental
      methods. With increases in computing power and innovations with computer
      hardware, more and more accurate techniques for modeling biological systems at
      the atomic level are under development. Here, we discuss two enzyme systems that
      illustrate the utility of dynamic simulations in conjunction with experimental
      studies. The first involves the use of X-ray crystal structures, kinetic studies,
      and molecular dynamics simulations in the study of the reduction of the prodrug
      CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) by the flavoenzyme nitroreductase
      from Escherichia coli. The second involves the study of the mechanism of the
      Salmonella serovars phosphothreonine lyase SpvC using X-ray crystal structures,
      biochemical assays, molecular dynamics simulations, and potential mean force
      calculations. It is only through a combination of experimental and computational
      techniques that a thorough atomic-level understanding of these enzyme reaction
      mechanisms is achieved.

PMID- 22607760
TI  - The increasing role of QM/MM in drug discovery.
AB  - Since its first appearance in 1976, the quantum mechanics/molecular mechanics
      (QM/MM) approach has mostly been used to study the chemical reactions of enzymes,
      which are frequently the target of drug discovery programs. In principle, a
      detailed understanding of the enzymatic mechanism should help researchers to
      design a potent enzyme inhibitor or new drug. However, QM/MM has not yet had a
      widespread impact on structure-based drug design. This is mostly due to its high
      computational cost. We expect this to change with the recent and extraordinary
      increases in computational power, and with the availability of more efficient
      algorithms for QM/MM calculations. Here, we report on some representative
      examples of QM/MM studies, including our own research, of pharmaceutically
      relevant enzymes, such as ribonuclease H and fatty acid amide hydrolase (FAAH).
      We aim to show how QM/MM has traditionally been used to study enzymatic
      catalysis. In this regard, we discuss its potential to become a routinely used
      drug design tool. To support this, we also discuss selected computational studies
      where QM/MM insights have been helpful in improving the potency of covalent
      inhibitors of FAAH.

PMID- 22607762
TI  - Using a combination of computational and experimental techniques to understand
      the molecular basis for protein allostery.
AB  - Allostery is the process by which remote sites of a system are energetically
      coupled to elicit a functional response. The early models of allostery such as
      the Monod-Wyman-Changeux model and the Koshland-Nemethy-Filmer model explain the
      allosteric behavior of multimeric proteins. However, these models do not explain
      how allostery arises from atomic level in detail. Recent developments in
      computational methods and experimental techniques have led the beginning of a new
      age in studying allostery. The combination of computational methods and
      experiments is a powerful research approach to help answering questions regarding
      allosteric mechanism at atomic resolution. In this review, three case studies are
      discussed to illustrate how this combined approach helps to increase our
      understanding of protein allostery.

PMID- 22607761
TI  - Allostery and binding cooperativity of the catalytic subunit of protein kinase A
      by NMR spectroscopy and molecular dynamics simulations.
AB  - The catalytic subunit of cAMP-dependent protein kinase A (PKA-C) is an exquisite
      example of a single molecule allosteric enzyme, where classical and modern views
      of allosteric signaling merge. In this chapter, we describe the mapping of PKA-C
      conformational dynamics and allosteric signaling in the free and bound states
      using a combination of NMR spectroscopy and molecular dynamics simulations. We
      show that ligand binding affects the enzyme's conformational dynamics, shaping
      the free-energy landscape toward the next stage of the catalytic cycle. While
      nucleotide and substrate binding enhance the enzyme's conformational entropy and
      define dynamically committed states, inhibitor binding attenuates the internal
      dynamics in favor of enthalpic interactions and delineates dynamically quenched
      states. These studies support a central role of conformational dynamics in many
      aspects of enzymatic turnover and suggest future avenues for controlling
      enzymatic function.

PMID- 22607763
TI  - Color shifting at the border of resin composite restorations in human tooth
      cavity.
AB  - OBJECTIVES: The purposes of this study were to evaluate color shifting at the
      boarder of resin composite restorations after placement in human tooth cavities
      in vitro. METHODS: Twenty extracted human premolars with an A2 shade were used in
      this study. Cylindrical shaped cavities (3.0mm or 1.5mm depth; 2.0mm diameter)
      were prepared in the center of the crowns. One of four resin composites of A2
      shade (Clearfil AP-X, AP; Clearfil Majesty, MA; Tetric N Ceram, TNC; Ceram X
      mono, CX) was placed in the cavity, and the color was measured at four points
      (0.4mm * 0.4mm) on the restored teeth (area 1: tooth area 1.0mm away from the
      border of resin composite restoration; area 2: tooth border area 0.3mm away from
      margin of resin composite restoration; area 3: resin composite border area 0.3mm
      away from margin of resin composite restoration; area 4: resin composite area at
      the center of resin composite restoration) using a spectrophotometer
      (Crystaleye). The color of each area was determined according to the CIELAB color
      scale. Color differences (DeltaE*) between the areas of 1 and 2, 2 and 3, 3 and
      4, and 1 and 4 were calculated, and also the ratio of DeltaE*23 to DeltaE*14 as a
      parameter of the color shifting at the border of resin composite restoration, was
      determined. The data were statistically analyzed using two-way ANOVA, and
      Dunnett's T3 and t-test for the post hoc test. RESULTS: For all materials, the
      Delta*23 were significantly lower than DeltaE*14, in which DeltaE*23 were
      significantly influenced by the materials although there were no significant
      differences in the DeltaE*14 between the materials. Additionally, DeltaE*12 were
      significantly higher than DeltaE*34. For the 3.0mm cavity depth group, the lowest
      DeltaE*23/14 ratio was seen in CX = <TNC<AP. For the 1.5mm cavity depth group,
      TNC dramatically reduced the DeltaE*23/14 ratio, and the lowest ratio was seen in
      TNC = CX<MJ<AP. SIGNIFICANCE: All resin composite restorations in the tooth
      cavities produced the color shifting of resin composite and tooth at the border.
      For deep cavity, resin composites with higher diffused light transmission
      property showed higher color shifting at the border, while for shallow cavity,
      the straight-line as well as diffused light transmission of resin composite
      affected the color shifting at the border. Clinically, diffused light
      transmission property of resin composites may contribute to the color shifting at
      the border of resin composite restoration regardless of cavity depth, resulting
      in better color matching.

PMID- 22607764
TI  - Sorption and solubility characteristics of self-adhesive resin cements.
AB  - OBJECTIVE: The aim of this in vitro study was to evaluate some sorption
      characteristics [sorption (S), solubility (SL) and the percentages of mass change
      (M(g)%), solubility (SL%) as well as sorbed liquid (S%)] of self-adhesive resin
      cements when immersed in distilled water and lactic acid. METHODS: A disc-shaped
      specimen of each self-adhesive resin cements [G-Cem (GC), SmartCemTM 2 (SC2),
      RelyXTM U100 (R1), RelyXTM Unicem 2 (RU2)] were prepared in a split-Teflon mold
      and irradiated by an Optilux 501 light cure at 580mW/cm(2) for 40s in eight
      overlapping sections each side. The volume of each specimen was calculated and
      placed inside a desiccator containing anhydrous calcium chloride, then weighed on
      an analytical electronic balance. Two independent groups were established
      according to the immersion media or liquids (distilled water and 0.01M lactic
      acid) maintained at 37 degrees C for the time intervals: 1, 6, 12, 24, 48 and
      168h, where the sorption (S) property (MUg/mm(3)) was calculated. However, the
      SL, M(g)%, SL% and S% were measured after 168h of immersion. The data were
      statistically analyzed by repeated measures ANOVA, one-way ANOVA and post hoc
      Tukey's test (p<0.05). RESULTS: Analysis of variance revealed highly significant
      differences between the materials for the sorption and solubility values examined
      with some exceptions (p<0.05). However, independent samples T-test expressed
      significant differences of all the sorption values between both water and lactic
      acid media for the resin cements with some border significances (p>0.05). The
      highest liquid's sorption was exhibited by GC material after immersion in lactic
      acid for 168h period followed by SC2 (37.83 and 34.15MUg/mm(3), respectively),
      while the lowest sorption was presented by RU2 cement after 1h immersion period
      in water (3.89MUg/mm(3)). Stereomicroscope showed homogenous surface topography
      in RU2 and R1 samples, while some striated cracks and microvoids were observed in
      GC and SC2 materials, respectively. The SL values followed this order:
      RU2<R1<SC2<GC. SIGNIFICANCE: Knowing the best self-adhesive cement that can
      provide less sorption and solubility values will help the dentist to choose the
      most suitable luting material for indirect restorations.

PMID- 22607765
TI  - The next generation of biologic agents: therapeutic role in relation to existing
      therapies in metastatic breast cancer.
AB  - The use of more active cytotoxic agents (eg, anthracyclines and taxanes) in the
      adjuvant setting has impacted treatment options in metastatic breast cancer
      (MBC). Various new approaches to combination therapy are being investigated,
      including classic and novel cytotoxic agents and targeted therapies. The
      heterogeneous molecular pathways involved in the development of breast cancer
      provide numerous potential targets for therapeutic intervention. Molecular
      technologies have facilitated the development of various new therapies targeted
      at disrupting processes as diverse as angiogenesis and DNA repair. Targeted
      therapies have the potential to improve outcomes in MBC, and their use has
      increased dramatically over recent years after the introduction of human
      epidermal growth factor receptor 2 (EGFR2)-targeted therapy with trastuzumab.
      Lapatinib and bevacizumab have recently been approved for patients with MBC.
      Numerous other targeted agents are undergoing preclinical investigation or are
      being evaluated in clinical trials. The maximum benefit of targeted therapies has
      been realized by their combined use with cytotoxic agents. Overall, single-agent
      use of targeted therapies has failed to produce dramatic benefit in patients with
      advanced breast cancer. This article reviews the data from studies of established
      and emerging targeted therapies in the treatment of MBC and describes how best to
      incorporate these agents into current treatment paradigms.

PMID- 22607766
TI  - A phase I study of ixabepilone in combination with epirubicin in patients with
      metastatic breast cancer.
AB  - In this phase I trial, 42 women with metastatic breast cancer were treated with a
      fixed dose of epirubicin (75 mg/m2) and escalating doses of ixabepilone (25, 30,
      and 35 mg/m2). The maximum-tolerated dose of ixabepilone in combination with
      epirubicin was 30 mg/m2 (the recommended dose for phase II evaluation), and the
      dose-limiting toxicity dose was 35 mg/m2 with grade 4 neutropenia. PURPOSE: The
      objectives of this phase I trial were to determine the maximum-tolerated dose
      (MTD), toxicity profile, dose-limiting toxicities (DLT), pharmacokinetics, and
      the recommended phase II dose for ixabepilone in combination with epirubicin in
      women with metastatic breast cancer. PATIENTS AND METHODS: Patients >=18 years
      old with an histologically or cytologically confirmed diagnosis of invasive
      breast cancer and clinical evidence of locally recurrent or metastatic disease
      were enrolled and treated with a fixed dose of epirubicin (75 mg/m(2)) and
      escalating doses of ixabepilone (25, 30, and 35 mg/m(2)). RESULTS: Forty-two
      women were treated at 3 different dose levels of ixabepilone: 25 (n = 6), 30 (n =
      30), and 35 mg/m(2) (n = 6) in combination with 75 mg/m(2) epirubicin. The MTD of
      ixabepilone in combination with epirubicin 75 mg/m(2) was 30 mg/m(2), and the DLT
      dose was 35 mg/m(2) with grade 4 neutropenia. Grade 3/4 neutropenia was the most
      frequent moderate-to-severe adverse event and was manageable and reversible. No
      deaths were reported. Objective responses were achieved in 18 of 32 patients with
      measurable disease (56% [90% CI, 40%-71%]) and in 9 of 22 evaluable patients
      treated at the MTD (41% [90% CI, 23%-61%]). Ixabepilone clearance and the
      epirubicin pharmacokinetic profile were similar across ixabepilone dose levels.
      CONCLUSIONS: The combination of ixabepilone and epirubicin was clinically active.
      The recommended dose for evaluation in phase II is epirubicin 75 mg/m(2),
      followed by ixabepilone 30 mg/m(2) every 3 weeks.

PMID- 22607767
TI  - Effect of different doses of metformin on serum testosterone and insulin in non
      diabetic women with breast cancer: a randomized study.
AB  - This is a randomized controlled trial to test the effect of different doses of
      metformin in patients with breast cancer and without diabetes, with the aim of
      modifying the hormonal and metabolic parameters linked to breast cancer
      prognosis. Analysis of the results suggest that the dose of 1500 mg/d of
      metformin causes a significant reduction of insulin and testosterone serum
      levels. BACKGROUND: Serum levels of insulin and testosterone may affect both
      breast cancer (BC) incidence and prognosis. Metformin reduces hyperglycemia and
      insulin levels in patients with diabetes. In women without diabetes and with
      polycystic ovary syndrome, metformin lowers both insulin and testosterone levels.
      Patients with diabetes who are treated with metformin showed a lower risk of
      cancer; a protective effect of metformin also was observed for BC. Recently,
      studies on metformin use for prevention or treatment of BC have been proposed in
      patients who are not diabetic. The aim of the present study was to test the
      effect of different doses of metformin on serum levels of insulin and
      testosterone in those postmenopausal patients with breast cancer and without
      diabetes who have basal testosterone levels >=0.28 ng/mL (median value). PATIENTS
      AND METHODS: A total of 125 eligible women were initially invited to take
      metformin 500 mg/d for 3 months. The 108 women who completed the first 3 months
      were invited to continue the study with metformin 1000 mg/d (500 mg twice a day
      [b.i.d.]) for 1 month. The women were then randomized into 2 groups, and, for the
      subsequent 5 months, 1 group increased the dose by taking metformin 1500 mg/d
      (500 mg 3 times a day [t.i.d.]), and the other group continued with metformin
      1000 mg /d (500 [b.i.d.]). RESULTS: A total of 96 women completed the study: 43
      women received 1500 mg/d, and 53 women received 1000 mg/d. The women who took
      1500 mg/d showed a significant reduction of insulin level, HOMA-IR index
      (homeostasis model assessment-insulin resistance index), testosterone level, and
      free androgen index compared with women treated with 1000 mg/d. After treatment
      with 1500 mg/d, the insulin level decreased by 25% and the testosterone level
      decreased by 23%. CONCLUSION: Both these changes might have a prognostic
      importance.

PMID- 22607768
TI  - Improved outcome of high-risk early HER2 positive breast cancer with high CXCL13
      CXCR5 messenger RNA expression.
AB  - The CXCL13-CXCR5 is a chemokine axis that is activated in some breast cancers. A
      total of 321 tissue blocks from a group of patients who received adjuvant, dose
      dense chemotherapy for high-risk early breast cancer were examined. Activation of
      this axis was found to be associated with determinants of poor prognosis but also
      with improved outcome in the human epidermal growth factor receptor 2
      overexpressing subpopulation. BACKGROUND: Chemokines are important in cell
      migration and are thought to play a key role in metastasis. We explored the
      prognostic significance of C-X-C ligand-motif (CXCL) 12, CXCL13, and receptor
      (CXCR) 5 on disease-free survival (DFS) and overall survival (OS) in early breast
      cancer. METHODS: A total of 595 patients with high risk, [corrected] early breast
      cancer were treated in a 2-arm trial (HE10/97) with dose-dense sequential
      epirubicin followed by cyclophosphamide, methotrexate, and 5-fluorouracil (CMF)
      with or without paclitaxel. RNA was extracted from 321 formalin-fixed paraffin
      embedded primary tumor tissue samples and quantitative reverse-transcriptase
      polymerase chain reaction was used to assess messenger RNA (mRNA) expression of
      CXCL12, CXCL13, and CXCR5; estrogen receptor; progesterone receptor (PgR);
      microtubule-associated protein tau and human epidermal growth factor receptor 2
      (HER2). RESULTS: CXCL13 and CXCR5 were found to be negatively associated with
      estrogen receptor and microtubule-associated protein tau mRNA expression and with
      dense lymphocytic infiltration, and were positively associated with nuclear
      grade. Only CXCL13 was positively associated with HER2. Multivariate analysis
      revealed an association between high CXCL13 mRNA expression and improved DFS
      (hazard ratio [HR] 0.48 [95% CI, 0.25-0.90]; Wald, P = .023) but not OS; whereas
      high CXCL12 expression was significantly associated with increased OS (HR 0.53
      [95% CI, 0.33-0.85]; Wald, P = .009). In the HER2 mRNA overexpressing subgroup,
      high CXCL13 mRNA expression was associated with improved DFS (P < .001), whereas
      high CXCR5 was associated with increased DFS and OS (P = .004 and P = .049,
      respectively). CONCLUSIONS: The CXCL13-CXCR5 axis is associated with classic
      determinants of poor prognosis, such as high grade, hormone receptor negativity,
      and axillary node involvement. Interestingly, this chemokine axis seems to be
      strongly associated with improved outcome in patients with HER2(+) disease.

PMID- 22607769
TI  - MicroRNA regulation of lipid metabolism.
AB  - MicroRNAs are structural components of an epigenetic mechanism of post
      transcriptional regulation of messenger RNA translation. Recently, there is
      significant interest in the application of microRNA as a blood-based biomarker of
      underlying physiologic conditions, and the therapeutic administration of microRNA
      inhibitors and mimics. The purpose of this review is to describe the current body
      of knowledge on microRNA regulation of genes involved in lipid metabolism, and to
      introduce the role of microRNA in development and progression of atherosclerosis.

PMID- 22607770
TI  - Loss of toll-like receptor 3 function improves glucose tolerance and reduces
      liver steatosis in obese mice.
AB  - OBJECTIVE: Emerging evidence suggests a link between innate immunity and
      development of type 2 diabetes mellitus (T2D); however, the molecular mechanisms
      linking them are not fully understood. Toll-like Receptor 3 (TLR3) is a pathogen
      pattern recognition receptor that recognizes the double-stranded RNA of microbial
      or mammalian origin and contributes to immune responses in the context of
      infections and chronic inflammation. The objective of this study was to determine
      whether TLR3 activity impacts insulin sensitivity and lipid metabolism. MATERIALS
      AND METHODS: Wild type (WT) and TLR3 knock-out (TLR3(-/-)) mice were fed a high
      fat diet (HFD) and submitted to glucose tolerance tests (GTTs) over a period of
      33 weeks. In another study, the same group of mice was treated with a
      neutralizing monoclonal antibody (mAb) against mouse TLR3. RESULTS: TLR3(-/-)
      mice fed an HFD developed obesity, although they exhibited improved glucose
      tolerance and lipid profiles compared with WT obese mice. In addition, the
      increase in liver weight and lipid content normally observed in WT mice on an HFD
      was significantly ameliorated in TLR3(-/-) mice. These changes were accompanied
      by up-regulation of genes involved in cholesterol efflux such as PPARdelta,
      LXRalpha, and LXRalpha-targeting genes and down-regulation of pro-inflammatory
      cytokine and chemokine genes in obese TLR3(-/-) mice. Furthermore, global gene
      expression profiling in liver demonstrated TLR3-specific changes in both lipid
      biosynthesis and innate immune response pathways. CONCLUSIONS: TLR3 affects
      glucose and lipid metabolism as well as inflammatory mediators, and findings in
      this study reveal a new role for TLR3 in metabolic homeostasis. This suggests
      antagonizing TLR3 may be a beneficial therapeutic approach for the treatment of
      metabolic diseases.

PMID- 22607771
TI  - Supplementing sow gestation diets with betaine during summer increases litter
      size of sows with greater numbers of parities.
AB  - Conducted during the Australian summer, this experiment evaluated the
      reproductive performance of sows receiving a diet supplemented with betaine, a
      potent organic osmolyte and methyl donor. Large White/Landrace/Duroc sows (n=450)
      ranging in parity from 1 to 7 (parity 2.9 +/- 0.10, mean +/- SEM), and mated
      between the 11th of January and 11th February were used. The treatments compared
      the effects of two gestation diets (standard (Stand) compared to betaine (Bet)
      supplemented) and two parity groups (parities one and two (P1/2) versus parity
      three and greater (P3+) on pregnancy outcomes and litter size. The betaine diet
      was fed from d 3 +/- 1 post-mating until farrowing, with betaine content of the
      diet altered during gestation to ensure a daily intake of 7.6-9.0 g/sow.
      Liveweight (LW) and LW gain were unaffected by gestation diet; however, on d 1 of
      lactation P2 backfat (P2) tended (P=0.07) to be greater for standard compared to
      betaine fed sows (22.5 +/- 0.42 compared to 21.5 +/- 0.42 mm). P2, LW and LW gain
      were greater (P<0.05) for P3+ compared to P1/2 sows. Sow farrowing rate (0.79)
      was unaffected by gestation diet. Total litter size was greater (P<0.05) for
      Bet3+ (13.6 +/- 0.35) sows compared to Stand3+ (12.1 +/- 0.34), BetP1/2 (12.1 +/-
      0.36) and StandP1/2 (12.3 +/- 0.38) sows. In conclusion, this is the first study
      to demonstrate that gestational betaine supplementation during summer increased
      litter size of sows with greater numbers of parities.

PMID- 22607772
TI  - Influence of zona pellucida thickness on fertilization, embryo implantation and
      birth.
AB  - Defective sperm-zona pellucida binding and penetration are the main causes of IVF
      failure. The purpose of this study was to evaluate the effect of zona pellucida
      thickness in fertilization failure and test the influence of zona pellucida
      thickness on implantation and birth in rabbits. Embryos and oocytes were
      collected from 72 females on Day 2 post-insemination. A total of 559 normal
      embryos were recovered; 402 embryos were transferred by laparoscopy and 157
      embryos were used to measure the zona pellucida thickness using the ImageJ
      program. Laparoscopies were also performed on all does at Day 12 of gestation to
      record the number of implanted embryos. Litter size at birth was recorded. The
      mean zona pellucida thickness of the 157 embryos and of the 64 control group
      oocytes (18.3 +/- 0.2 and 18.5 +/- 0.3 MUm, respectively) was significantly less
      than the zona pellucida thickness of the 74 failed fertilization oocytes (19.2 +/
      0.3 MUm). The probabilities of the regression coefficient being positive were
      0.72 and 0.74 for implantation and birth, respectively, and the subsequent means
      of the coefficient were 2.92 and 0.03 for implantation and birth, respectively.
      In conclusion, the zona pellucida thickness has an important influence on in vivo
      fertilization and implantation processes, but not on birth.

PMID- 22607773
TI  - In Italy, healthy life expectancy drop dramatically: from 2004 to 2008 there was
      a 10 years drop among newborn girls.
AB  - INTRODUCTION: In this short essay, we would like to address a severe divergence
      observed in Italy between Life Expectancy (LE) and Healthy Life Expectancy
      (Healthy LE) and a unique trend of worsening in Healthy LE, compared to the other
      European countries. Both issues emerge in recent data by EUROSTAT Report.
      METHODS: The analysis used by the authors of the EUROSTAT report is based on
      Sullivan method which combines 2 type of variables: mortality and morbidity data.
      RESULTS: While several European countries started to deal with comparable data
      about LE since 1960, in Italy, analogous data were available for the first time
      in EUROSTAT Report only in 1985. In Italy, in the period 1985-2008, there was a
      good progressive increase in L.E., following the best European values.
      Nevertheless, while until 2004 Italy was among the European best countries in
      terms of both LE and Healthy LE at birth, four years later in 2008 there was a
      shocking loss of 10 years of Healthy LE at birth in newborn girls. In the
      process, they lost their 2-years previous advantage with respect to males (the
      latter lost only 6 years of Healthy LE, in the same time span). Looking at
      healthy LE at age 65 in respect to 2004, Italian women in 2008 could expect to
      live healthy only about 7 years (as much as men) versus the almost 15 years of
      the European best values (14 years for men). CONCLUSIONS: It is legitimate to
      wonder why no one official comment has been produced as a reaction after the
      first year of spectacular decline in Healthy Life Years in Italy: in counter
      tendency with European values, from 2004 to 2008 there is a clear evidence of a
      10 years drop in Healthy LE among newborn girls. The problem has not been taken
      into consideration even when the situation clearly appeared to worsen in the
      following years, dropping 4-6 more years for males and females in 2006 (for
      newborn babies); two more years of healthy life expectancy have been lost between
      2006 and 2007 for each gender. One more year of Healthy Life Expectancy is lost
      in 2008. And data have not been made available any more, since then, from Italy.

PMID- 22607774
TI  - Could piracetam potentiate behavioural effects of psychostimulants?
AB  - Press and internet reports mention abuse of nootropic drug piracetam (PIR) in
      combination with psychostimulants methamphetamine (MET) or 4
      methylenedioxymethamphetamine (MDMA). These combinations are believed to produce
      more profound desirable effects, while decreasing hangover. However, there is a
      lack of valid experimental studies on such drug-drug interactions in the
      scientific literature available. Our hypothesis proposes that a functional
      interaction exists between PIR and amphetamine psychostimulants (MET and MDMA)
      which can potentiate psychostimulant behavioural effects. Our hypothesis is
      supported by the results of our pilot experiment testing acute effects of drugs
      given to mice intraperitoneally (Vehicle, n=12; MET 2.5mg/kg, n=10; MDMA
      2.5mg/kg, n=11; PIR 300 mg/kg, n=12; PIR+MET, n=12; PIR+MDMA, n=11) in the Open
      Field Test (Actitrack, Panlab, Spain). PIR given alone caused no significant
      changes in mouse locomotor/exploratory behaviour, whereas the same dose combined
      with either MET or MDMA significantly enhanced their stimulatory effects.
      Different possible neurobiological mechanism underlying drug-drug interaction of
      PIR with MET or MDMA are discussed, as modulation of dopaminergic, glutamatergic
      or cholinergic brain systems. However, the interaction with membrane
      phospholipids seems as the most plausible mechanism explaining PIR action on
      activities of neurotransmitter systems. Despite that our behavioural experiment
      cannot serve for explanation of the pharmacological mechanisms of these
      functional interactions, it shows that PIR effects can increase behavioural
      stimulation of amphetamine drugs. Thus, the reported combining of PIR with MET or
      MDMA by human abusers is not perhaps a coincidental phenomenon and may be based
      on existing PIR potential to intensify acute psychostimulant effects of these
      drugs of abuse.

PMID- 22607775
TI  - Hepatitis e virus infection in sheltered homeless persons, france.

PMID- 22607776
TI  - Consent in psychiatric biobanks for pharmacogenetic research.
AB  - In psychiatric practice, pharmacogenetics has the potential to identify patients
      with an increased risk of unsatisfactory drug responses. Genotype-guided
      treatment adjustments may increase benefits and reduce harm in these patients;
      however, pharmacogenetic testing is not (yet) common practice and more
      pharmacogenetic research in psychiatric patients is warranted. An important
      precondition for this type of research is the establishment of biobanks. In this
      paper, we argue that, for the storage of samples in psychiatric biobanks, waiving
      of consent is not ethically justifiable since the risks cannot be considered
      minimal and the argument of impracticability does not apply. An opt-out consent
      procedure is also not justifiable, since it presumes competence while the
      decisional competence of psychiatric patients needs to be carefully evaluated. We
      state that an enhanced opt-in consent procedure is ethically necessary, i.e. a
      procedure that supports the patients' decision-making at the time when the
      patient is most competent. Nevertheless, such a procedure is not the traditional
      exhaustive informed consent procedure, since this is not feasible in the case of
      biobanking.

PMID- 22607777
TI  - Modeling suggests that gene circuit architecture controls phenotypic variability
      in a bacterial persistence network.
AB  - BACKGROUND: Bacterial persistence is a non-inherited bet-hedging mechanism where
      a subpopulation of cells enters a dormant state, allowing those cells to survive
      environmental stress such as treatment with antibiotics. Persister cells are not
      mutants; they are formed by natural stochastic variation in gene expression.
      Understanding how regulatory architecture influences the level of phenotypic
      variability can help us explain how the frequency of persistence events can be
      tuned. RESULTS: We present a model of the regulatory network controlling the
      HipBA toxin-antitoxin system from Escherichia coli. Using a biologically
      realistic model we first determine that the persistence phenotype is not the
      result of bistability within the network. Next, we develop a stochastic model and
      show that cells can enter persistence due to random fluctuations in
      transcription, translation, degradation, and complex formation. We then examine
      alternative gene circuit architectures for controlling hipBA expression and show
      that networks with more noise (more persisters) and less noise (fewer persisters)
      are straightforward to achieve. Thus, we propose that the gene circuit
      architecture can be used to tune the frequency of persistence, a trait that can
      be selected for by evolution. CONCLUSIONS: We develop deterministic and
      stochastic models describing how the regulation of toxin and antitoxin expression
      influences phenotypic variation within a population. Persistence events are the
      result of stochastic fluctuations in toxin levels that cross a threshold, and
      their frequency is controlled by the regulatory topology governing gene
      expression.

PMID- 22607778
TI  - How best to assess the quality of life in long-term survivors after surgery for
      NSCLC? Comparison between clinical predictors and questionnaire scores.
AB  - BACKGROUND: The determinants and predictors of QOL in lung cancer survivors who
      have received surgery remain defined vaguely and still debated. We evaluate
      clinical, surgical, and pulmonary function characteristics as predictors of QOL
      in long-term lung cancer survivors who received surgery. METHODS: Quality of life
      was evaluated 5 years after surgery in 67 lung cancer patients using the European
      Organization for Research and Treatment of Cancer (EORTC) QOL Core Questionnaire,
      its lung cancer-specific module QLQ LC-13, and the Hospital Anxiety and
      Depression Scale questionnaire. Preoperative clinical, surgical, and pathologic
      data were matched with the questionnaire scores. RESULTS: Sex was associated with
      role functioning and symptoms, with males more often reporting fatigue and pain,
      appetite loss, coughing, and hemoptysis (P < .05). Lower education was associated
      with better cognitive functioning (P < .05). Symptoms were worse for younger
      patients and for those with major comorbidity. Histology marginally influenced
      the global health status (P < .10) and the cognitive functioning (P < .05).
      Patients receiving complementary therapy more easily suffered from fatigue and
      insomnia (P < .05), and to a lesser extent from nausea and vomiting,
      constipation, and stress related to financial difficulties (P < .10). Higher
      values of forced expiratory volume at the first second (FEV(1)) and forced vital
      capacity (FVC) were significantly (P < .05) associated with a lower frequency of
      nausea and vomiting and appetite loss, while low percentage levels of FEV(1) and
      FVC were associated with lower global function and a greater severity of specific
      and nonspecific symptoms (P < .10 and P < .05). CONCLUSIONS: Several preoperative
      features, particularly those reflecting pulmonary function, were moderately
      associated with QOL in long-term survivors and may be useful to address
      therapeutic strategies in lung cancer patients after surgery.

PMID- 22607779
TI  - Gefitinib-related interstitial lung disease in Taiwanese patients with non-small
      cell lung cancer.
AB  - BACKGROUND: Gefitinib (Iressa; AstreZeneca, Wilmington, DE) is effective in the
      treatment of NSCLC, especially in the Asian population. However, ILD is usually a
      serious pulmonary adverse effect and almost leads to cessation of gefitinib
      treatment. In this study, we investigated the incidence, clinical features, and
      prognosis of gefitinib-related ILD in Taiwanese patients with NSCLC. PATIENTS AND
      METHODS: This was a retrospective observational study conducted in 2 medical
      centers and a local teaching hospital. RESULTS: A total of 1080 patients with
      NSCLC, who received at least 1 dose (250 mg per day) of gefitinib treatment, were
      enrolled. Of these, 42 patients were diagnosed with ILD. Twenty-five of the 42
      patients were diagnosed with gefitinib-related ILD (incidence, 2.3%). The main
      manifestations of ILD included dyspnea, cough, and hypoxemia. Six of the 25
      patients (24%) with gefitinib-related ILD required invasive mechanical
      ventilation and all patients were treated with steroids. Twenty-two patients
      (88%) discontinued gefitinib treatment without further rechallenge. Ten (40%)
      patients died directly from ILD and in-hospital mortality was 52%. Eleven
      patients received subsequent cytotoxic chemotherapy with a mean of 33.5 days
      after ILD events. Kaplan-Meier analysis demonstrated that gefitinib nonresponder
      and gefitinib use rather than first-line treatment were associated with poor
      prognosis when ILD developed during gefitinib treatment. CONCLUSION: Taiwanese
      patients with NSCLC had a relatively high incidence of ILD during gefitinib
      treatment. Gefitinib-related ILD is usually life-threatening, especially in
      gefitinib nonresponders and gefitinib use rather than first-line treatment.

PMID- 22607780
TI  - Effects of aerobic endurance, muscle strength, and motor control exercise on
      physical fitness and musculoskeletal injury rate in preprofessional dancers: an
      uncontrolled trial.
AB  - OBJECTIVE: The purpose of this study was to evaluate musculoskeletal injury rate
      and physical fitness before and 6 months after an endurance, strength, and motor
      control exercise program in preprofessional dancers. METHODS: This uncontrolled
      trial was completed at a college offering a professional bachelor degree in
      dance. Forty preprofessional dancers underwent a test battery before and after a
      6-month lasting exercise program in addition to their regular dance lessons.
      Physical fitness was evaluated by means of a submaximal exercise test with
      continuous physiological monitoring and by a field test for explosive strength.
      Anthropometric measurements were taken to analyze the influence of fitness
      training on body composition. Musculoskeletal injury incidence and quality of
      life were recorded during the 6-month lasting intervention. An intention-to-treat
      analysis ("last observation carried forward" method) was used with a Student t
      test for normally distributed variables. The Wilcoxon signed rank and Mann
      Whitney U tests were used as nonparametric tests. RESULTS: Physical fitness
      improved after the 6 months of additional training program (P<.05). The waist:hip
      ratio (P=.036) and the sum of the measured subcutaneous skin thickness (P=.001)
      significantly decreased. Twelve dancers developed musculoskeletal complaints,
      requiring temporary interruption of dancing. CONCLUSIONS: The combination of
      regular dance lessons with an additional exercise program resulted in improved
      physical fitness in preprofessional dancers, without affecting the aesthetical
      appearance. A relatively high injury rate was observed during the intervention
      period. These results suggest that a randomized, controlled trial should be
      performed to examine the effectiveness of additional exercise in dancers on
      physical fitness and musculoskeletal injury rate.

PMID- 22607781
TI  - Evaluation of changes in pelvic belt tension during 2 weight-bearing functional
      tasks.
AB  - OBJECTIVE: The purposes of this study were to evaluate changes in pelvic belt
      tension during 2 weight-bearing functional tasks (transition from bipedal to
      unipedal stance [BUS] and walking) and to evaluate the reliability and the
      percentage variation for belt tension scores from trial to trial. METHODS: A
      cross-sectional repeated-measures study was conducted with 10 healthy male
      participants (mean age, 28.3 +/- 8.8years). Participants performed 10 trials of
      BUS and walking while wearing a nonelastic pelvic compression belt (PCB) applied
      distal to the anterior superior iliac spines, with a load cell positioned in the
      center of the belt. The load cell was calibrated using known weights (1-10kg) to
      define the relationship between the applied tension and voltage change (R(2) =
      0.99). Load cell tension values were recorded in voltage signals and then
      converted to newtons of force using appropriate conversion values (0.012V = 10N).
      Mean and standard deviation values, intraclass correlation coefficients (ICC
      3,1), and percentage standard error of measurements (% SEM) were analyzed for PCB
      tension recorded during the BUS and walking trials. RESULTS: The mean tension
      achieved with a PCB was found to be 41.02 (+/-4.23) N during BUS and 44.07 (+/
      5.80) N during walking. The trial-to-trial reliability (ICC 3,1) was high (ICC
      >=0.9), and the variation in PCB tension across 10 trials (% SEM) was 4% or less.
      CONCLUSION: The mean tension achieved during the tasks was 44 N or less. The
      reliability is high, and the variation is low across the trials, which implies
      that a PCB could be used to produce consistent effects during repetition of the
      tasks (BUS and walking).

PMID- 22607782
TI  - Long-term outcomes after atrioventricular valve operations in patients undergoing
      single-ventricle palliation.
AB  - BACKGROUND: Outcomes after atrioventricular (AV) valve operations in patients
      with functional single ventricles are unclear. METHODS: From 1988 to 2010, 76
      consecutive patients with single ventricles underwent AV valve operations for
      regurgitation at a single institution. Five replacements, 66 repairs, and 5 valve
      closures were performed at a median age of 1 year (range, 1 day-14 years) on 43
      tricuspid, 9 mitral, and 24 common AV valves. RESULTS: Hospital mortality was 17%
      (13/76). The follow-up was 100% complete. There were 15 late deaths. There were
      48 survivors with a mean follow-up of 8.3+/-6 years. One- and 10-year Kaplan
      Meier survival after AV valve operations was 72% (95% confidence interval [CI],
      60%-81%) and 61% (95% CI, 48%-71%), respectively. Independent predictors of
      overall mortality were presence of a common AV valve (p=0.03), requirement for
      postoperative mechanical circulatory support (p=0.02), and timing of valve
      operations between initial palliation and performance of a bidirectional
      cavopulmonary shunt (BCPS) (p=0.047). Ten-year freedom from valve reoperation and
      from thromboembolic events of hospital survivors was 56% (95% CI, 38%-70%) and
      70% (95% CI, 56%-80%), respectively. At last follow-up, 11 of 48 surviving
      patients (23%) had moderate to severe regurgitation, and pacemaker implantation
      was required in 6 patients. Only 34 patients reached the stage of Fontan
      completion. CONCLUSIONS: AV valve regurgitation is a considerable burden for the
      patient with a single ventricle, especially when appearing at a young age. A
      quarter of patients died within the first year after operation, and they had
      considerable morbidity in terms of reoperation, thromboembolic events, and
      pacemaker implantation. Their chances of reaching Fontan completion seemed
      decreased.

PMID- 22607783
TI  - Mitral valve repair is durable in patients with rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) and its treatments are associated with
      tissue abnormalities, which may influence surgical outcomes of repair for severe
      mitral valve regurgitation (MR). We examined late survival and durability of
      mitral valve repair in patients with RA. METHODS: Thirty-six patients with RA (21
      male) underwent mitral valve repair for MR from August 1978 to August 2005.
      Median age was 70 years (range, 22 to 84). Preoperatively, 27 patients (75%) had
      New York Heart Association Functional Class III/IV symptoms, and 29 (78%)
      required immunomodulating medications for RA management. Mechanisms of MR were
      leaflet prolapse in 26 patients (72%), leaflet malcoaptation in 5 (14%),
      tethering in 4 (11%), and unknown in 1 (3%). RESULTS: All patients underwent
      mitral valve repair, which included posterior leaflet triangular resection in 11
      patients, leaflet plication in 10, and artificial chordae placement in 3. When
      compared with matched control patients without RA who underwent mitral valve
      repair, RA patients had decreased survival (27% versus 64%, p=0.005) and freedom
      from reoperation (93% versus 98%, p=0.04) at 8 years. However, RA patients
      undergoing mitral valve repair had similar survival at 5 years compared with age-
      and sex-matched comparator patients with RA who did not undergo mitral valve
      surgery (65% versus 67%, p=nonsignificant). CONCLUSIONS: Mitral leaflet pathology
      in RA patients with severe MR is similar to that of non-RA patients with mitral
      valve disease. Long-term survival after mitral valve repair in RA patients is
      equivalent to that of the general RA population without mitral valve disease, and
      the durability of mitral valve repair in these patients is very good.

PMID- 22607784
TI  - The long-term outcome of open valvotomy for critical aortic stenosis in neonates.
AB  - BACKGROUND: This study analyzed the long-term outcome after operations for open
      aortic valvotomy, specifically looking at the preservation of the native aortic
      valve. METHODS: Between 1983 and 2011, 34 neonates with critical aortic stenosis
      underwent open valvotomy. The mean age at operation was 15 days (range, 1 to 28
      days). Follow-up was 100% complete. RESULTS: Three patients died early. The
      probability of survival was 91.2%, with a mean follow-up of 11 years (range, 10
      months to 21 years). Event-free survival was 77%, 68%, 68%, and 57% at 5, 10, 15,
      and 20 years, respectively, and freedom from aortic valve replacement was 93%,
      83%, 68%, and 57%. Tricuspid valve morphology revealed the best outcome, with
      event-free survival of 90% (p = 0.006) and 100% freedom from aortic valve
      replacement (p = 0.0012) at 20 years of follow-up. All but 4 patients were in New
      York Heart Association class I; 77 % of all patients were without medication.
      CONCLUSIONS: In neonates, predictable and consistent long-term results can be
      accomplished by open valvotomy in any type of valve morphology, even in an
      asymmetric arrangement. Operative repair not only offers a 90% survival benefit
      in the long-term but also preserves the native aortic valve in most patients.
      Clearly superior results were achieved in tricuspid valve morphology, in which
      there was no need for aortic valve replacement at 20 years of follow-up.

PMID- 22607785
TI  - Morbid obesity is associated with increased resource utilization in coronary
      artery bypass grafting.
AB  - BACKGROUND: Studies have shown good outcomes for morbidly obese patients who
      undergo cardiac surgery. However, little is known about how much additional
      resource utilization treating these challenging patients requires. We
      hypothesized that morbidly obese patients (body mass index >=40 kg/m(2))
      undergoing coronary artery bypass grafting needed longer operating room times and
      had longer hospital and intensive care unit stays than non-morbidly obese
      patients. METHODS: We reviewed data from all morbidly obese patients (n = 56,
      body mass index = 42.7 +/- 2.6 kg/m(2)) who underwent coronary artery bypass
      grafting at our institution between 1999 and 2009. These patients' outcomes were
      compared with those of non-morbidly obese patients (n = 168, body mass index =
      30.0 +/- 2.8 kg/m(2)) who were propensity-matched 3:1 with the morbidly obese
      patients. RESULTS: Of the 14 preoperative characteristics examined, only 1,
      creatinine level, differed significantly between the two groups (p = 0.02).
      Intraoperative and postoperative complication rates and the mortality rate were
      similar between groups (p > 0.09). However, morbidly obese patients had longer
      operating times (449 +/- 70 versus 420 +/- 59 minutes; p = 0.002), intensive care
      unit stays (5.2 versus 3.3 days; p < 0.005), and postoperative hospital stays
      (14.2 versus 9.5 days; p < 0.005) than the non-morbidly obese patients.
      CONCLUSIONS: Although good outcomes can be achieved for morbidly obese patients
      who undergo coronary artery bypass grafting, these patients require considerably
      more resource utilization in the operating room and intensive care unit, and they
      spend more time in the hospital after surgery. At a cardiac surgical operating
      room cost of approximately $50 per minute and $4,500 per intensive care unit day,
      the financial implications for morbidly obese patients who need coronary artery
      bypass grafting are not insignificant.

PMID- 22607787
TI  - Outcomes of the arterial switch operation for transposition of the great
      arteries: 25 years of experience.
AB  - BACKGROUND: Studies on long-term outcomes of the arterial switch operation (ASO)
      for transposition of the great arteries (TGA) are uncommon. Thus, we sought to
      determine the long-term outcomes for patients after ASO performed at a single
      institution over a 25-year period. METHODS: From 1983 to 2009, 618 patients
      underwent the ASO for TGA and were reviewed retrospectively. RESULTS: Overall
      early mortality was 2.8%. Risk factors for early death on multivariate analysis
      were resection of left ventricular outflow tract obstruction at time of ASO (p =
      0.001), weight less than 2.5 kg at time of ASO (p < 0.001), associated aortic
      arch obstruction (p = 0.043), and the need for postoperative extracorporeal
      membrane oxygenation (p < 0.001). Mean follow-up time was 10.6 years (range 2
      months to 26.1 years). Late mortality was 0.9%. Reintervention was significantly
      higher (p < 0.001) in patients with ventricular septal defect or arch obstruction
      versus those without them (25.2% and 23.4% vs 5.9% at 15- year follow-up). Risk
      factors for late reintervention were left ventricular outflow tract obstruction
      at time of ASO (p < 0.001) and a greater circulatory arrest time (p < 0.001).
      Freedom from at least moderate neoaortic valve regurgitation for the entire
      cohort was 98.7% (95% confidence interval 96.8 to 99.5%) at 20 years. Mild
      neoaortic regurgitation was seen in 25.6% of patients at mean follow-up. All
      patients were free of arrhythmia and heart failure symptoms at last follow-up.
      CONCLUSIONS: The ASO can be performed with good long-term results. Patients with
      associated ventricular septal defect and aortic arch obstruction warrant close
      follow-up.

PMID- 22607786
TI  - Concomitant tricuspid valve operations affect outcomes after mitral operations: a
      multiinstitutional, statewide analysis.
AB  - BACKGROUND: Mitral valve (MV) disease is often accompanied by concomitant
      tricuspid valve (TV) disease. This study determined the influence of performing
      TV procedures in the setting of MV operations within a multiinstitutional patient
      population. METHODS: From 2001 to 2008, 5,495 MV operations were performed at 17
      different statewide centers. Of these, 5,062 patients (age, 63.4 +/- 13.0 years)
      underwent an MV operation and 433 (age, 64.0 +/- 14.2 years) underwent combined
      MV and TV (MV+TV) operations. The influence of concomitant TV procedures on
      operative death and the composite incidence of major complications was assessed
      by univariate and multivariate analyses. RESULTS: Patients undergoing MV+TV were
      more commonly women (62.7% vs 45.5%, p < 0.001), had higher rates of heart
      failure (73.7% vs 50.9%, p < 0.001), and more frequently underwent reoperations
      (17.1% vs 7.4%, p < 0.001) compared with MV patients. Other patient
      characteristics, including preoperative endocarditis (8.5% vs 8.2%, p = 0.78),
      were similar between groups. MV replacement (63.5%) was more common than repair
      (36.5%, p < 0.001) in MV+TV operations, and MV+TV operations incurred longer
      median cardiopulmonary bypass times (181 vs 149 minutes, p < 0.001). Unadjusted
      operative mortality (6.0% vs 10.4%, p = 0.001) and postoperative complications
      were higher after MV+TV compared with MV. More important, risk adjustment showed
      performance of concomitant TV procedures was an independent predictor of
      operative death (odds ratio, 1.50; p = 0.03) and major complications (odds ratio,
      1.39; p = 0.004). CONCLUSIONS: A concomitant TV operation is a proxy for more
      advanced valve disease. Compared with MV operations alone, simultaneous MV+TV
      operations are associated with elevated morbidity and death, even after risk
      adjustment. This elevated risk should be considered during preoperative patient
      risk stratification.

PMID- 22607788
TI  - Risk factors for intraoperative atrial fibrillation: a retrospective analysis of
      10,563 lung operations in a single center.
AB  - BACKGROUND: Risk factors of postoperative atrial fibrillation (AF) in patients
      undergoing general thoracic operations have been extensively studied. This study
      investigated risk factors for intraoperative AF. Identification of patients
      vulnerable for intraoperative AF during lung operations will benefit from
      improved preoperative and intraoperative management that will ultimately decrease
      intraoperative complications. This study retrospectively evaluated the risk
      factors for intraoperative AF during lung operations. METHODS: Medical records of
      10,638 patients who underwent lung operations from January 1, 2006, to May 20,
      2011, at the Shanghai Chest Hospital were reviewed. The analysis excluded 75
      patients with preoperative AF or nonsinus rhythm or who were taking
      antiarrhythmic drugs before the operation. The final analysis included 10,563
      patients. Univariate and multivariate analyses were performed to identify risk
      factors for intraoperative AF. RESULTS: The overall incidence of intraoperative
      AF was 3.27% (346 of 10,563). Multivariable logistic analysis identified
      increasing age, male sex, lung cancer, general anesthesia plus paravertebral
      block, open operation, resection of one or more lobes, and increased operation
      time as risk factors of intraoperative AF. In 40.73% of patients, intraoperative
      AF occurred during lymph node dissection. CONCLUSIONS: We identified seven risk
      factors for intraoperative AF in patients receiving lung operations. These
      findings may eventually help us to improve preoperative and intraoperative
      management to minimize intraoperative AF.

PMID- 22607789
TI  - Increased septum wall thickness in patients undergoing aortic valve replacement
      predicts worse late survival.
AB  - BACKGROUND: Following guidelines, aortic valve replacement (AVR) in asymptomatic
      patients with severe aortic valve stenosis is often postponed until symptoms do
      occur. Delaying AVR will inevitably lead to progression of left ventricular
      hypertrophy. We studied the relationship between septum wall thickness indexed
      for body surface area (SWTI) as a measure for LV hypertrophy and 30-day and late
      all-cause mortality after AVR. METHODS: This study included the data of adult
      patients who underwent isolated AVR between January 2006 and December 2010 and in
      whom a reliable measurement of the septum wall thickness could be made. The
      patients were stratified into three groups according to their SWTI. The SWTI was
      less than 6 mm/m(2) in 136 patients, between 6 and 8 mm/m(2) in 307 patients, and
      more than 8 mm/m(2) in 126 patients. RESULTS: Death occurred in 10 patients
      within 30 days (1.8%), and 41 patients died during follow-up (7.2%). Univariate
      logistic regression analysis revealed only endocarditis as predictor of early
      mortality. Multivariate Cox regression analyses revealed SWTI as a continuous
      variable as well as a categorical (group) variable to be a predictor of late
      mortality. Compared with the group SWTI less than 6 mm/m(2), odds ratio for the
      group with SWTI 6 to 8 mm/m(2) was 3.4 (p = 0.046), and for the group with SWTI
      more than 8 mm/m(2), it was 6.0 (p = 0.005). CONCLUSIONS: In patients undergoing
      AVR, the SWTI was a strong predictor of late mortality. Whether avoidance of
      progression of left ventricular hypertrophy by early AVR leads to better outcome
      remains to be investigated.

PMID- 22607790
TI  - Aortic arch repair with antegrade selective cerebral perfusion using mild to
      moderate hypothermia of more than 28 degrees C.
AB  - BACKGROUND: The temperature at circulatory arrest during open distal anastomosis
      is the most significant issue for aortic arch repair. In many institutions, there
      has been trend toward raising the temperature during circulatory arrest. METHODS:
      Between 2004 and 2011, 164 consecutive patients underwent aortic arch repair with
      antegrade selective cerebral perfusion (ASCP) and moderate hypothermia. The
      patients were divided into two subsets (n = 84 each): group A (circulatory arrest
      at less than 27.9 degrees C) and group B (at more than 28 degrees C). RESULTS: In
      group A compared with group B, mean temperature at circulatory arrest was 26
      degrees  +/- 1.0 degrees C vs 29 degrees  +/- 1.0 degrees C, mean ASCP time was
      72 +/- 23 minutes vs 67 +/- 17 minutes, and mean circulatory arrest time was 47
      +/- 21 minutes vs 44 +/- 13 minutes. The 30-day mortality was 6.1% in both
      groups. Permanent neurologic deficit occurred in 8 patients (9.8%) in group A and
      in 5 (6.1%) in group B (p = 0.39). The incidence of renal failure requiring
      hemodialysis was 14.6% in group A and 3.6% in group B (p = 0.02). Postoperative
      respiratory failure requiring mechanical ventilation exceeding 3 days occurred in
      12.2% of patients in group A and in 7.3% in group B (p = 0.04). CONCLUSIONS: The
      temperature during ASCP can be safely increased to more than 28 degrees C without
      increasing the rate of mortality and morbidity. ASCP with moderate hypothermia
      offered sufficient cerebral and distal organ protection.

PMID- 22607791
TI  - Comparing the reliability of a trigonometric technique to goniometry and
      inclinometry in measuring ankle dorsiflexion.
AB  - OBJECTIVES: The purpose of this study was to compare the reliability of three
      previously used techniques for the measurement of ankle dorsiflexion ROM, open
      chained goniometry, closed-chained goniometry, and inclinometry, to a novel
      trigonometric technique. METHODS: Twenty-one physiotherapy students used four
      techniques (open-chained goniometry, closed-chained goniometry, inclinometry, and
      trigonometry) to assess dorsiflexion range of motion in 24 healthy volunteers.
      All student raters underwent training to establish competence in the four
      techniques. Raters then measured dorsiflexion with a randomly assigned measuring
      technique four times over two sessions, one week apart. Data were analyzed using
      a technique by session analysis of variance, technique measurement variability
      being the primary index of reliability. Comparisons were also made between the
      measurements derived from the four techniques and those obtained from a
      computerized video analysis system. RESULTS: Analysis of the rater measurement
      variability around the technique means revealed significant differences between
      techniques with the least variation being found in the trigonometric technique.
      Significant differences were also found between the technique means but no
      differences between sessions were evident. The trigonometric technique produced
      mean ROMs closest in value to those derived from computer analysis. CONCLUSIONS:
      Application of the trigonometric technique resulted in the least variability in
      measurement across raters and consequently should be considered for use when
      changes in dorsiflexion ROM need to be reliably assessed.

PMID- 22607792
TI  - The influence of hip abductor muscle performance on dynamic postural stability in
      females with patellofemoral pain.
AB  - Hip abductors play an important role in maintaining trunk and pelvis stability
      during unipedal tasks. The purpose of the study was to compare postural stability
      between individuals with patellofemoral pain (PFP) and pain-free controls. A
      secondary purpose was to evaluate the effect of a hip stabilizing brace on
      postural stability. Twenty females with PFP (27.3+/-6.3 years) and 19 controls
      (26.1+/-4.5 years) participated. Each subject performed a unipedal step-down
      balance task with the stance leg on a force platform from which center of
      pressure (COP) excursion was recorded. Quantitative COP excursion patterns (mean
      and peak displacements) were used as measures of postural stability. For subjects
      with PFP, postural stability also was quantified following the application of a
      hip stabilizing brace. Hip abductor strength was significantly lower in PFP group
      compared to the control group (1.39+/-0.4 vs. 1.62+/-0.26 N/kg-BW, p=0.046). Peak
      and mean medial-lateral COP displacements during the balance task were greater in
      the PFP group (39.8+/-6.7 vs. 24.3+/-3.8 mm, p<0.001; 24.7+/-16.3 vs. 13.5+/-4.4
      mm, p=0.005). Application of the hip stabilizing brace reduced the peak and mean
      COP displacement (39.8+/-6.7 vs. 24.7+/-4.7 mm, p<0.001; 24.7+/-16.3 vs. 16.8+/
      15.1 mm, p=0.02). Our results demonstrate that females with PFP exhibit impaired
      medial-lateral postural stability when compared to control subjects. Application
      of a hip stabilizing brace significantly improved stability to a level comparable
      to the controls.

PMID- 22607793
TI  - Old antibiotics target TB with a new trick.
AB  - Autophagy is now recognized as a cellular defense mechanism that can restrict the
      growth of Mycobacterium tuberculosis (Mtb). In this issue of Cell Host & Microbe,
      Kim et al. (2012) demonstrate that antibiotics routinely used to treat Mtb
      infection elicit a host autophagy response critical for bacterial clearance.

PMID- 22607794
TI  - Viral infection brings mitochondrial traffic to a standstill.
AB  - Mitochondria are dynamic organelles with many functions. In this issue of Cell
      Host & Microbe, Kramer and Enquist (2012) show that mitochondrial motility and
      morphology are disrupted during alphaherpesvirus infection, which aids viral
      replication and transport in neurons.

PMID- 22607795
TI  - Exciting developments in the immunology of fungal infections.
AB  - The last decade has brought significant advances in our understanding of
      antifungal immunity, which offer hope for the development of novel
      immunotherapeutics. In this commentary, we provide a snapshot of the protective
      innate and adaptive components of antifungal immunity and highlight several
      recent topics of interest, placing in context the three associated reviews in
      this issue of Cell Host & Microbe.

PMID- 22607796
TI  - Th17 cells in immunity to Candida albicans.
AB  - Our understanding of immunity to fungal pathogens has advanced considerably in
      recent years. Particularly significant have been the parallel discoveries in the
      C-type lectin receptor family and the Th effector arms of immunity, especially
      Th17 cells and their signature cytokine, IL-17. Many of these studies have
      focused on the most common human fungal pathogen, Candida albicans, which is
      typically a commensal microbe in healthy individuals but causes various disease
      manifestations in immunocompromised hosts, ranging from mild mucosal infections
      to lethal disseminated disease. Here, we discuss emerging fundamental discoveries
      with C. albicans that have informed our overall molecular understanding of fungal
      immunity. In particular, we focus on the importance of pattern recognition
      receptor-mediated fungal recognition and subsequent IL-17 responses in host
      defense against mucosal candidiasis. In light of these recent advances, we also
      discuss the implications for anticytokine biologic therapy and vaccine
      development.

PMID- 22607797
TI  - Dendritic cells in antifungal immunity and vaccine design.
AB  - Life-threatening fungal infections have increased in recent years while treatment
      options remain limited. The development of vaccines against fungal pathogens
      represents a key advance sorely needed to combat the increasing fungal disease
      threat. Dendritic cells (DC) are uniquely able to shape antifungal immunity by
      initiating and modulating naive T cell responses. Targeting DC may allow for the
      generation of potent vaccines against fungal pathogens. In the context of
      antifungal vaccine design, we describe the characteristics of the varied DC
      subsets, how DC recognize fungi, their function in immunity against fungal
      pathogens, and how DC can be targeted in order to create new antifungal vaccines.
      Ongoing studies continue to highlight the critical role of DC in antifungal
      immunity and will help guide DC-based vaccine strategies.

PMID- 22607798
TI  - Immunoglobulins in defense, pathogenesis, and therapy of fungal diseases.
AB  - Only two decades ago antibodies to fungi were thought to have little or no role
      in protection against fungal diseases. However, subsequent research has provided
      convincing evidence that certain antibodies can modify the course of fungal
      infection to the benefit or detriment of the host. Hybridoma technology was the
      breakthrough that enabled the characterization of antibodies to fungi,
      illuminating some of the requirements for antibody efficacy. As discussed in this
      review, fungal-specific antibodies mediate protection through direct actions on
      fungal cells and through classical mechanisms such as phagocytosis and complement
      activation. Although mechanisms of antibody-mediated protection are often species
      specific, numerous fungal antigens can be targeted to generate vaccines and
      therapeutic immunoglobulins. Furthermore, the study of antibody function against
      medically important fungi has provided fresh immunological insights into the
      complexity of humoral immunity that are likely to apply to other pathogens.

PMID- 22607799
TI  - Host cell autophagy activated by antibiotics is required for their effective
      antimycobacterial drug action.
AB  - The current standard of treatment against tuberculosis consists of a cocktail of
      first-line drugs, including isoniazid and pyrazinamide. Although these drugs are
      known to be bactericidal, contribution of host cell responses in the context of
      antimycobacterial chemotherapy, if any, remains unknown. We demonstrate that
      isoniazid and pyrazinamide promote autophagy activation and phagosomal maturation
      in Mycobacterium tuberculosis (Mtb)-infected host cells. Treatment of Mtb
      infected macrophages with isoniazid or pyrazinamide caused significant activation
      of cellular and mitochondrial reactive oxygen species and autophagy, which was
      triggered by bacterial hydroxyl radical generation. Mycobacterium marinum
      infected autophagy-defective, atg7 mutant Drosophila exhibited decreased survival
      rates, which could not be rescued by antimycobacterial treatment, indicating that
      autophagy is required for effective antimycobacterial drug action in vivo.
      Moreover, activation of autophagy by antibiotic treatment dampened Mtb-induced
      proinflammatory responses in macrophages. Together, these findings underscore the
      importance of host autophagy in orchestrating successful antimicrobial responses
      to mycobacteria during chemotherapy.

PMID- 22607800
TI  - Mycobacterium tuberculosis activates the DNA-dependent cytosolic surveillance
      pathway within macrophages.
AB  - Cytosolic bacterial pathogens activate the cytosolic surveillance pathway (CSP)
      and induce innate immune responses, but how the host detects vacuolar pathogens
      like Mycobacterium tuberculosis is poorly understood. We show that M.
      tuberculosis also initiates the CSP upon macrophage infection via limited
      perforation of the phagosome membrane mediated by the ESX-1 secretion system.
      Although the bacterium remains within the phagosome, this permeabilization
      results in phagosomal and cytoplasmic mixing and allows extracellular
      mycobacterial DNA to access host cytosolic receptors, thus blurring the
      distinction between "vacuolar" and "cytosolic" pathogens. Activation of cytosolic
      receptors induces signaling through the Sting/Tbk1/Irf3 axis, resulting in IFN
      beta production. Surprisingly, Irf3(-/-) mice, which cannot respond to cytosolic
      DNA, are resistant to long-term M. tuberculosis infection, suggesting that the
      CSP promotes M. tuberculosis infection. Thus, cytosolic sensing of mycobacterial
      DNA plays a key role in M. tuberculosis pathogenesis and likely contributes to
      the high type I IFN signature in tuberculosis.

PMID- 22607802
TI  - Bornavirus closely associates and segregates with host chromosomes to ensure
      persistent intranuclear infection.
AB  - Bornaviruses are nonsegmented negative-strand RNA viruses that establish a
      persistent infection in the nucleus and occasionally integrate a DNA genome copy
      into the host chromosomal DNA. However, how these viruses achieve intranuclear
      infection remains unclear. We show that Borna disease virus (BDV), a mammalian
      bornavirus, closely associates with the cellular chromosome to ensure
      intranuclear infection. BDV generates viral factories within the nucleus using
      host chromatin as a scaffold. In addition, the viral ribonucleoprotein (RNP)
      interacts directly with the host chromosome throughout the cell cycle, using core
      histones as a docking platform. HMGB1, a host chromatin-remodeling DNA
      architectural protein, is required to stabilize RNP on chromosomes and for
      efficient BDV RNA transcription in the nucleus. During metaphase, the association
      of RNP with mitotic chromosomes allows the viral RNA to segregate into daughter
      cells and ensure persistent infection. Thus, bornaviruses likely evolved a
      chromosome-dependent life cycle to achieve stable intranuclear infection.

PMID- 22607801
TI  - Emergence of distinct multiarmed immunoregulatory antigen-presenting cells during
      persistent viral infection.
AB  - During persistent viral infection, adaptive immune responses are suppressed by
      immunoregulatory factors, contributing to viral persistence. Although this
      suppression is mediated by inhibitory factors, the mechanisms by which virus
      specific T cells encounter and integrate immunoregulatory signals during
      persistent infection are unclear. We show that a distinct population of IL-10
      expressing immunoregulatory antigen-presenting cells (APCs) is amplified during
      chronic versus acute lymphocytic choriomeningitis virus (LCMV) infection and
      suppresses T cell responses. Although acute LCMV infection induces the expansion
      of immunoregulatory APCs, they subsequently decline. However, during persistent
      LCMV infection, immunoregulatory APCs are amplified and parallel the viral
      replication kinetics. Further characterization demonstrates that immunoregulatory
      APCs are molecularly and metabolically distinct, and exhibit increased expression
      of T cell-interacting molecules and negative regulatory factors that suppress T
      cell responses. Thus, immunoregulatory APCs are amplified during viral
      persistence and deliver inhibitory signals that suppress antiviral T cell
      immunity and likely contribute to persistent infection.

PMID- 22607803
TI  - Alphaherpesvirus infection disrupts mitochondrial transport in neurons.
AB  - Mitochondria are dynamic organelles that are essential for cellular metabolism
      but can be functionally disrupted during pathogen infection. In neurons,
      mitochondria are transported on microtubules via the molecular motors kinesin-1
      and dynein and recruited to energy-requiring regions such as synapses. Previous
      studies showed that proteins from pseudorabies virus (PRV), an alphaherpesvirus,
      localize to mitochondria and affect mitochondrial function. We show that PRV and
      herpes simplex virus type 1 (HSV-1) infection of rodent superior cervical
      ganglion (SCG) neurons disrupts mitochondrial motility and morphology. During PRV
      infection, glycoprotein B (gB)-dependent fusion events result in electrical
      coupling of neurons and increased action potential firing rates. Consequently,
      intracellular [Ca(2+)] increases and alters mitochondrial dynamics through a
      mechanism involving the Ca(2+)-sensitive cellular protein Miro and reduced
      recruitment of kinesin-1 to mitochondria. This disruption in mitochondrial
      dynamics is required for efficient growth and spread of PRV, indicating that
      altered mitochondrial transport enhances alphaherpesvirus pathogenesis and
      infection.

PMID- 22607804
TI  - Toxoplasma sortilin-like receptor regulates protein transport and is essential
      for apical secretory organelle biogenesis and host infection.
AB  - Apicomplexan parasites have an assortment of unique apical secretory organelles
      (rhoptries and micronemes), which have crucial functions in host infection. Here,
      we show that a Toxoplasma gondii sortilin-like receptor (TgSORTLR) is required
      for the subcellular localization and formation of apical secretory organelles.
      TgSORTLR is a transmembrane protein that resides within Golgi-endosomal related
      compartments. The lumenal domain specifically interacts with rhoptry and
      microneme proteins, while the cytoplasmic tail of TgSORTLR recruits cytosolic
      sorting machinery involved in anterograde and retrograde protein transport.
      Ectopic expression of the N-terminal TgSORTLR lumenal domain results in dominant
      negative effects with the mislocalization of both endogenous TgSORTLR as well as
      rhoptry and microneme proteins. Conditional ablation of TgSORTLR disrupts rhoptry
      and microneme biogenesis, inhibits parasite motility, and blocks both invasion
      into and egress from host cells. Thus, the sortilin-like receptor is essential
      for protein trafficking and the biogenesis of key secretory organelles in
      Toxoplasma.

PMID- 22607805
TI  - The mitochondrial targeting chaperone 14-3-3epsilon regulates a RIG-I translocon
      that mediates membrane association and innate antiviral immunity.
AB  - RIG-I is a cytosolic pathogen recognition receptor that initiates immune
      responses against RNA viruses. Upon viral RNA recognition, antiviral signaling
      requires RIG-I redistribution from the cytosol to membranes where it binds the
      adaptor protein, MAVS. Here we identify the mitochondrial targeting chaperone
      protein, 14-3-3epsilon, as a RIG-I-binding partner and essential component of a
      translocation complex or "translocon" containing RIG-I, 14-3-3epsilon, and the
      TRIM25 ubiquitin ligase. The RIG-I translocon directs RIG-I redistribution from
      the cytosol to membranes where it mediates MAVS-dependent innate immune signaling
      during acute RNA virus infection. 14-3-3epsilon is essential for the stable
      interaction of RIG-I with TRIM25, which facilitates RIG-I ubiquitination and
      initiation of innate immunity against hepatitis C virus and other pathogenic RNA
      viruses. Our results define 14-3-3epsilon as a key component of a RIG-I
      translocon required for innate antiviral immunity.

PMID- 22607807
TI  - The effectiveness of physiotherapy exercises in subacromial impingement syndrome:
      a systematic review and meta-analysis.
AB  - OBJECTIVE: To evaluate the effectiveness of exercise in the treatment of people
      with subacromial impingement syndrome (SAIS). METHODS: A systematic review and
      meta-analysis were conducted. Ten electronic databases were searched from the
      dates of their inception until August 2010. Included studies were randomized
      controlled trials investigating exercise in the management of SAIS. Outcomes were
      pain, strength, function, and quality of life. Data were summarized qualitatively
      using a best evidence synthesis. Treatment effect size and variance of individual
      studies were used to give an overall summary effect and data were converted to
      standardized mean difference with 95% confidence intervals (standardized mean
      difference (SMD) (CI)). RESULTS: Sixteen studies were included (n = 1162). There
      was strong evidence that exercise decreases pain and improves function at short
      term follow-up. There was also moderate evidence that exercise results in short
      term improvement in mental well-being and a long-term improvement in function for
      those with SAIS. The most common risk of bias across the studies was inadequately
      concealed treatment allocation. Six studies in the review were suitable for meta
      analysis. Exercise had a small positive effect on strength of the rotator cuff in
      the short term (SMD -0.46 (-0.76, 0.16); P = 0.003) and a small positive effect
      on long-term function (SMD -0.31 (-0.57, 0.04); P = 0.02). CONCLUSIONS:
      Physiotherapy exercises are effective in the management of SAIS. However,
      heterogeneity of the exercise interventions, coupled with poor reporting of
      exercise protocols, prevented conclusions being drawn about which specific
      components of the exercise protocols (ie, type, intensity, frequency and
      duration) are associated with best outcomes.

PMID- 22607806
TI  - A widespread bacterial type VI secretion effector superfamily identified using a
      heuristic approach.
AB  - Sophisticated mechanisms are employed to facilitate information exchange between
      interfacing bacteria. A type VI secretion system (T6SS) of Pseudomonas aeruginosa
      was shown to deliver cell wall-targeting effectors to neighboring cells. However,
      the generality of bacteriolytic effectors and, moreover, of antibacterial T6S
      remained unknown. Using parameters derived from experimentally validated
      bacterial T6SS effectors we identified a phylogenetically disperse superfamily of
      T6SS-associated peptidoglycan-degrading effectors. The effectors separate into
      four families composed of peptidoglycan amidase enzymes of differing
      specificities. Effectors strictly co-occur with cognate immunity proteins,
      indicating that self-intoxication is a general property of antibacterial T6SSs
      and effector delivery by the system exerts a strong selective pressure in nature.
      The presence of antibacterial effectors in a plethora of organisms, including
      many that inhabit or infect polymicrobial niches in the human body, suggests that
      the system could mediate interbacterial interactions of both environmental and
      clinical significance.

PMID- 22607808
TI  - Iatrogenic Creutzfeldt-Jakob disease, final assessment.
AB  - The era of iatrogenic Creutzfeldt-Jakob disease (CJD) has nearly closed; only
      occasional cases with exceptionally long incubation periods are still appearing.
      The principal sources of these outbreaks are contaminated growth hormone (226
      cases) and dura mater grafts (228 cases) derived from human cadavers with
      undiagnosed CJD infections; a small number of additional cases are caused by
      neurosurgical instrument contamination, corneal grafts, gonadotrophic hormone,
      and secondary infection with variant CJD transmitted by transfusion of blood
      products. No new sources of disease have been identified, and current practices,
      which combine improved recognition of potentially infected persons with new
      disinfection methods for fragile surgical instruments and biological products,
      should continue to minimize the risk for iatrogenic disease until a blood
      screening test for the detection of preclinical infection is validated for human
      use.

PMID- 22607809
TI  - Prevalence, quantification and antimicrobial resistance of Campylobacter spp. on
      chicken neck-skins at points of slaughter in 5 major cities located on 4
      continents.
AB  - Quantitative data on Campylobacter contamination of food are lacking, notably in
      developing countries. We assessed Campylobacter contamination of chicken neck
      skins at points of slaughter in 5 major cities in Africa (Dakar in Senegal,
      Yaounde in Cameroon), Oceania (Noumea in New Caledonia), the Indian Ocean
      (Antananarivo in Madagascar) and Asia (Ho Chi Minh City (HCMC) in Vietnam. One
      hundred and fifty slaughtered chickens were collected in each of the 5 major
      cities from semi-industrial abattoirs or markets (direct slaughter by the
      seller), and 65.5% (491/750) were found to be Campylobacter-positive. Two cities,
      Yaounde and Noumea, demonstrated high prevalence Campylobacter detection rates
      (92.7% and 96.7% respectively) in contrast with HCMC (15.3%). Four species were
      identified among 633 isolates, namely C. jejuni (48.3%), C. coli (37.3%), C. lari
      (11.7%) and C. upsaliensis (1%). HCMC was the only city with C. lari isolation as
      was Antananarivo for C. upsaliensis. C. coli was highly prevalent only in Yaounde
      (69.5%). Among the 491 samples positive in Campylobacter detection, 329 were also
      positive with the enumeration method. The number of Campylobacter colony-forming
      units (CFU) per gram of neck-skin in samples positive in enumeration was high
      (mean of the log(10): 3.2 log(10) CFU/g, arithmetic mean: 7900CFU/g). All the
      cities showed close enumeration means except HCMC with a 1.81 log(10) CFU/g mean
      for positive samples. Semi-industrial abattoir was linked to a significant lower
      count of Campylobacter contamination than direct slaughter by the seller
      (p=0.006). On 546 isolates (546/633, 86.3%) tested for antibiotic susceptibility,
      resistance to erythromycin, ampicillin and ciprofloxacin was observed for
      respectively 11%, 19% and 50%. HCMC was the city where antibiotic resistant rates
      were the highest (95%, p=0.014). Considering the 329 positive chickens in
      Campylobacter enumeration, the mean number of resistant isolates to at least 2
      different antibiotic families (19.8%), may be estimated ca. 1500CFU/g; the
      corresponding mean of the log(10) would be 2.5 log(10)CFU/g. As chickens are sold
      at slaughter and brought directly at home to be cooked, these data suggest a high
      probability of cross-contamination. A substantial proportion of isolates are drug
      resistant, which could lead to potential public health issues. Health authorities
      should consider measures to reduce Campylobacter contamination of chicken during
      farming and at slaughter, and to provide appropriate food hygiene education.
      Further studies are needed in particular to investigate food-handling practices
      in domestic kitchens.

PMID- 22607810
TI  - Salmonella cross-contamination in swine abattoirs in Portugal: Carcasses, meat
      and meat handlers.
AB  - In this study the occurrence of Salmonella in swine, pork meat and meat handlers
      along with their clonal relatedness is evaluated at abattoir level. Samples from
      the lymph nodes, carcass surface and meat of 100 pigs and 45 meat handlers were
      collected in eight abattoirs (July 2007-August 2008). Salmonella isolates were
      serotyped and genotyped by pulsed-field gel electrophoresis (PFGE). From the pigs
      tested, 42 produced at least one positive sample. A relatively high frequency of
      Salmonella occurrence was found in the ileoceacal lymph node samples (26.0%),
      followed by carcass (16.0%) and meat samples (14.0%). However, ileoceacal lymph
      nodes that test positive for Salmonella are not found to be a predictor of
      positive test results further on in the process. Besides the slaughterhouse
      environment, meat handlers were identified as a possible source of subsequent
      contamination, with 9.3% of the sample testing positive. Diverse Salmonella
      enterica serotypes were detected, mainly S. Typhimurium and the monophasic
      variant S. 4,[5],12:i:-, but also S. Derby, S. Rissen, S. Mbandaka, S. London, S.
      Give, S. Enteritidis and S. Sandiego, in total corresponding to 17 PFGE types.
      Our results demonstrate that besides a high level of Salmonella swine
      contamination at pre-harvest level, slaughtering, dressing, cutting and deboning
      operations are contributing to the occurrence of clinically relevant clones (e.g.
      S. Typhimurium DT104 and S. 4,[5],12:i:-) in pork products. This study also
      highlights the possibility of an ongoing Salmonella community being spread by
      abattoir workers.

PMID- 22607811
TI  - Intraspecific variations of Dekkera/Brettanomyces bruxellensis genome studied by
      capillary electrophoresis separation of the intron splice site profiles.
AB  - In enology, "Brett" character refers to the wine spoilage caused by the yeast
      Dekkera/Brettanomyces bruxellensis and its production of volatile phenolic off
      flavours. However, the spoilage potential of this yeast is strain-dependent.
      Therefore, a rapid and reliable recognition at the strain level is a key point to
      avoid serious economic losses. The present work provides an operative tool to
      assess the genetic intraspecific variation in this species through the use of
      introns as molecular targets. Firstly, the available partial D./B. bruxellensis
      genome sequence was investigated in order to build primers annealing to introns
      5' splice site sequence (ISS). This analysis allowed the detection of a non
      random vocabulary flanking the site and, exploiting this feature, the creation of
      specific probes for strain discrimination. Secondly, the separation of the intron
      splice site PCR fragments was obtained throughout the set up of a capillary
      electrophoresis protocol, giving a 94% repeatability threshold in our
      experimental conditions. The comparison of results obtained with ISS-PCR/CE
      versus the ones performed by mtDNA RFLP revealed that the former protocol is more
      discriminating and allowed a reliable identification at strain level. Actually
      sixty D./B. bruxellensis isolates were recognised as unique strains, showing a
      level of similarity below 79% and confirming the high genetic polymorphism
      existing within the species. Two main clusters were grouped at similarity levels
      of about 46% and 47%, respectively, showing a poor correlation with the
      geographic area of isolation. Moreover, from the evolutionary point of view, the
      proposed technique could determine the frequency of the genome rearrangements
      that can occur in D./B. bruxellesis populations.

PMID- 22607812
TI  - Menopausal symptoms: do life events predict severity of symptoms in peri- and
      post-menopause?
AB  - OBJECTIVE: Hormonal changes during menopausal transition are linked to physical
      and psychological symptoms' emergence. This study aims to explore if life events
      predict menopausal symptoms. METHODS: This cross-sectional research encompasses a
      community sample of 992 women who answered to socio-demographic, health,
      menopause-related and lifestyle questionnaires; menopausal symptoms and life
      events were assessed with validated instruments. Structural equation modeling was
      used to build a causal model. RESULTS: Menopausal status predicted only three
      symptoms: skin/facial hair changes (beta=.136; p=.020), sexual (beta=.157;
      p=.004) and, marginally, vasomotor symptoms (beta=.094; p=.054). Life events
      predicted depressive mood (beta=-.391; p=.002), anxiety (beta=-.271; p=.003),
      perceived cognitive impairment (beta=-.295; p=.003), body shape changes (beta=
      .136; p=.031), aches/pain (beta=-.212; p=.007), skin/facial hair changes (beta=
      .171; p=.021), numbness (beta=-.169; p=.015), perceived loss of control (beta=
      .234; p=.008), mouth, nails and hair changes (beta=-.290; p=.004), vasomotor
      (beta=-.113; p=.044) and sexual symptoms (beta=-.208; p=.009). CONCLUSIONS:
      Although women in peri- and post-menopausal manifested higher symptoms' severity
      than their pre-menopausal counterparts, only three of the menopausal symptoms
      assessed were predicted by menopausal status. Since the vast majority of
      menopausal symptoms' severity was significantly influenced by the way women
      perceived their recent life events, it is concluded that the symptomatology
      exacerbation, in peri- and post-menopausal women, might be due to life conditions
      and events, rather than hormonal changes (nonetheless, the inverse influence
      should be investigated in future studies). Therefore, these should be accounted
      for in menopause-related clinical and research settings.

PMID- 22607813
TI  - Reminiscence therapy in dementia: a review.
AB  - Dementia is a progressive disorder that impacts several cognitive functions.
      However, some aspects of cognitive function are preserved until late in the
      disease and can therefore be the targets of specific interventions. The
      rehabilitation of cognitive function disorders represents an expanding area of
      neurological rehabilitation, and it has recently attracted growing political,
      social and ethical attention. Here, we review the efficacy of reminiscence
      therapy to improve cognitive functions and/or mood. Available studies suggest
      that reminiscence therapy can improve mood and some cognitive abilities. Further
      studies, based on larger patient samples including placebo and control
      conditions, should be conducted to identify the optimal conditions for such
      treatment protocols.

PMID- 22607814
TI  - Potential mechanisms of postmenopausal endometriosis.
AB  - Endometriosis is a chronic gynaecological disorder, the cause of which remains a
      subject of controversy. Oestrogen dependence is considered central to development
      and progression, and endometriosis is widely viewed as a disease of the
      premenopausal years, which normally regresses during the menopause. Increasingly
      however, reports of cases of postmenopausal endometriosis challenge our current
      understanding of the pathophysiology and raise further questions concerning the
      processes involved. Exploring the limited evidence available on postmenopausal
      disease we attempt to draw comparisons with pre-menopausal endometriosis, and in
      doing so to propose mechanisms for postmenopausal disease that are compatible
      with our current general understanding of the condition.

PMID- 22607815
TI  - Low-salt porcine serum concentrate as functional ingredient in frankfurters.
AB  - The objective was to assay the use of serum from porcine blood as functional
      ingredient in frankfurter production. Three pilot productions of sausages were
      carried out to compare serum containing frankfurters to sausages based on a
      standard commercial formula that included caseinate and polyphosphate. Both
      products were very similar for proximate composition, water holding capacity,
      cooking and purge losses, instrumental texture, and microstructure. The sensory
      descriptive profile and the overall acceptance were also comparatively evaluated.
      Although significantly higher values for the animal taste and odour attributes of
      sausages with serum compared to control ones were obtained, the differences were
      lower than those reported in a previous study using whole plasma. Thus,
      ultrafiltration could be useful to reduce animal off-flavour in blood-based
      protein ingredients. Moreover, overall acceptance did not significantly differ
      between the two types of products, being 6.7 and 6.5, for control and test
      sausages respectively.

PMID- 22607816
TI  - Cooked yields, color, tenderness, and sensory traits of beef roasts cooked in an
      oven with steam generation versus a commercial convection oven to different
      endpoint temperatures.
AB  - A CVap steam generation oven was compared with a Blodgett convection oven to
      examine effects on yields, cooked color, tenderness, and sensory traits of beef
      Longissimus lumborum (LL), Deep pectoralis (DP), and Biceps femoris (BF) muscles
      cooked to 1 of 3 temperatures (65.6, 71.1, or 76.7 degrees C). Four roasts were
      cooked in the CVap for a constant time, and 2 roasts were cooked in the Blodgett
      until they reached target temperatures (3 replications). Cooking yields were
      higher (P<0.05) for BF and LL roasts in the CVap. Slice shear force (SSF) for BF
      roasts was lowest (P<0.05) in the CVap but lowest (P<0.05) for DP roasts in the
      Blodgett. No oven effect (P>0.05) was found for LL roasts. Sensory tenderness for
      BF roasts in the CVap was higher (P<0.05) than those in the Blodgett. Juiciness
      was higher (P<0.05) for LL roasts in the Blodgett. The CVap oven offers some
      tenderization (BF) and cooking yield advantages (BF and DP) over forced-air
      convection cooking.

PMID- 22607817
TI  - 58th International Congress of Meat Science and Technology--ICoMST 2012.

PMID- 22607818
TI  - Facial injuries in Scotland 2001-2009: epidemiological and sociodemographic
      determinants.
AB  - To our knowledge, sociodemographic determinants of facial injuries in children
      have not previously been reported in Scotland. We analysed the pattern, time
      trends, and key sociodemographic determinants of facial injuries in children and
      adolescents using Scottish morbidity records for inpatient care (2001-2009) which
      were retrieved from the Information Services Division of National Health Services
      (NHS) Scotland. We calculated annual incidences by age, sex, health board,
      Scottish Index of Multiple Deprivation (SIMD), and mechanism of injury. A Poisson
      regression analysis model was used to incorporate the variables. A total of 45388
      patients aged from birth to 17 years sustained a facial injury (4.7/1000
      population over nine years); 60% (27101) of injuries were unintentional, 15%
      (6726) resulted from motor vehicle accidents, and 9% (4149) resulted from alleged
      assaults; 5% (2058) were alcohol related. The incidence decreased over time from
      5.5/1000 in 2001 to 4.0/1000 in 2009. The rate ratio for boys was 1.94 times
      greater than for girls (p<0.001), and it varied significantly between health
      board areas (0.68 in Dumfries and Galloway and 1.76 in Grampian) (p<0.001). There
      was a significant association between facial injury and increasing deprivation
      (p<0.001). The incidence of facial injury is highest among boys living in areas
      of high socioeconomic deprivation so education and resources should be directed
      towards prevention in these areas.

PMID- 22607819
TI  - Auditory brainstem response as a possible objective indicator for salicylate
      induced tinnitus in rats.
AB  - The auditory response to an acoustic stimulus will usually be suppressed, or
      masked, by a preceding sound. Here, we show that forward acoustic masking at a
      high frequency can boost the auditory brainstem response (ABR) in rats injected
      with a high dose of sodium salicylate (NaSal), a tinnitus inducer. The forward
      narrow band noise caused a decrease in the amplitude of the ABR to a probe tone
      burst in normal rats, but caused an unexpected increase in the amplitude at 16
      kHz in rats treated with NaSal (300 mg/kg). The observed effect could be
      manifested in normal rats presented with a background tone added to the masker
      and the probe, suggesting an underlying mechanism associated with tinnitus. We
      hypothesize that in NaSal-treated rats, tinnitus can "internally" mask the ABR in
      a similar way as an external background sound does and the "unmasking" effect of
      forward masking can result in a rebound of the otherwise suppressed ABR. Our
      study raises the possibility of using the ABR as an objective indicator for NaSal
      induced tinnitus in animals. This article is part of a Special Issue entitled:
      Tinnitus Neuroscience.

PMID- 22607820
TI  - Epidural motor cortex stimulation suppresses somatosensory evoked potentials in
      the primary somatosensory cortex of the rat.
AB  - Motor cortex stimulation (MCS) is a promising clinical procedure to help
      alleviate chronic pain. Animal models demonstrated that MCS is effective in
      lessening nocifensive behaviors. The present study explored the effects of MCS on
      cortical somatosensory evoked potentials (SEPs) recorded at the primary
      somatosensory cortex (SI) of the rat. SEPs were evoked by electrical stimulation
      applied to the contralateral forepaws. Effects of different intensities,
      frequencies, and durations of MCS were tested. MCS at >=2V suppressed SEPs of the
      ipsilateral SI. Suppression lasted 120 min at an intensity of 5 V. The optimal
      frequency was 50 Hz, and the duration was 30s. In contrast, MCS did not affect
      SEPs recorded on the contralateral SI. Cortical stimulation out of the motor
      cortex did not induce a decrease in the ipsilateral SEPs. We also investigated
      involvement of the endogenous opioid system in this inhibition of SEPs induced by
      MCS. The opioid antagonist, naloxone (0.5 mg/kg), was administered 30 min before
      MCS. Application of naloxone completely prevented the inhibitory effect of MCS on
      ipsilateral SEPs. These results demonstrate that MCS blocked the transmission of
      somatosensory information to the primary somatosensory cortex, and this
      interference was mediated by the endogenous opioid system. This inhibitory effect
      on sensory transmission induced by MCS may reflect its antinociceptive effect.

PMID- 22607821
TI  - Towards the creation of a flexible classification scheme for voluntarily reported
      transfusion and laboratory safety events.
AB  - BACKGROUND: Transfusion and clinical laboratory services are high-volume
      activities involving complicated workflows across both ambulatory and inpatient
      environments. As a result, there are many opportunities for safety lapses,
      leading to patient harm and increased costs. Organizational techniques such as
      voluntary safety event reporting are commonly used to identify and prioritize
      risk areas across care settings. Creation of functional, standardized safety data
      structures that facilitate effective exploratory examination is therefore
      essential to drive quality improvement interventions. Unfortunately, voluntarily
      reported adverse event data can often be unstructured or ambiguously defined.
      RESULTS: To address this problem, we sought to create a "best-of-breed" patient
      safety classification for data contained in the Duke University Health System
      Safety Reporting System (SRS). Our approach was to implement the internationally
      recognized World Health Organization International Classification for Patient
      Safety Framework, supplemented with additional data points relevant to our
      organization. Data selection and integration into the hierarchical framework is
      discussed, as well as placement of the classification into the SRS. We evaluated
      the impact of the new SRS classification on system usage through comparisons of
      monthly average report rates and completion times before and after
      implementation. Monthly average inpatient transfusion reports decreased from
      102.1 +/- 14.3 to 91.6 +/- 11.2, with the proportion of transfusion reports in
      our system remaining consistent before and after implementation. Monthly average
      transfusion report rates in the outpatient and homecare environments were not
      significantly different. Significant increases in clinical lab report rates were
      present across inpatient and outpatient environments, with the proportion of lab
      reports increasing after implementation. Report completion times increased
      modestly but not significantly from a practical standpoint. CONCLUSIONS: A common
      safety vocabulary can facilitate integration of information from disparate
      systems and processes to permit meaningful measurement and interpretation of data
      to improve safety within and across organizations. Formation of a "best-of-breed"
      classification for voluntary reporting necessitates an internal examination of
      localized data needs and workflow in order to design a product that enables
      comprehensive data capture. A team of clinical, safety, and information
      technology experts is necessary to integrate the data structures into the
      reporting system. We have found that a "best-of-breed" patient safety
      classification provides a solid, extensible model for adverse event analysis,
      healthcare leader communication, and intervention identification.

PMID- 22607823
TI  - Statins for all by the age of 50 years?

PMID- 22607824
TI  - Mendelian randomisation, lipids, and cardiovascular disease.

PMID- 22607822
TI  - The effects of lowering LDL cholesterol with statin therapy in people at low risk
      of vascular disease: meta-analysis of individual data from 27 randomised trials.
AB  - BACKGROUND: Statins reduce LDL cholesterol and prevent vascular events, but their
      net effects in people at low risk of vascular events remain uncertain. METHODS:
      This meta-analysis included individual participant data from 22 trials of statin
      versus control (n=134,537; mean LDL cholesterol difference 1.08 mmol/L; median
      follow-up 4.8 years) and five trials of more versus less statin (n=39,612;
      difference 0.51 mmol/L; 5.1 years). Major vascular events were major coronary
      events (ie, non-fatal myocardial infarction or coronary death), strokes, or
      coronary revascularisations. Participants were separated into five categories of
      baseline 5-year major vascular event risk on control therapy (no statin or low
      intensity statin) (<5%, >=5% to <10%, >=10% to <20%, >=20% to <30%, >=30%); in
      each, the rate ratio (RR) per 1.0 mmol/L LDL cholesterol reduction was estimated.
      FINDINGS: Reduction of LDL cholesterol with a statin reduced the risk of major
      vascular events (RR 0.79, 95% CI 0.77-0.81, per 1.0 mmol/L reduction), largely
      irrespective of age, sex, baseline LDL cholesterol or previous vascular disease,
      and of vascular and all-cause mortality. The proportional reduction in major
      vascular events was at least as big in the two lowest risk categories as in the
      higher risk categories (RR per 1.0 mmol/L reduction from lowest to highest risk:
      0.62 [99% CI 0.47-0.81], 0.69 [99% CI 0.60-0.79], 0.79 [99% CI 0.74-0.85], 0.81
      [99% CI 0.77-0.86], and 0.79 [99% CI 0.74-0.84]; trend p=0.04), which reflected
      significant reductions in these two lowest risk categories in major coronary
      events (RR 0.57, 99% CI 0.36-0.89, p=0.0012, and 0.61, 99% CI 0.50-0.74,
      p<0.0001) and in coronary revascularisations (RR 0.52, 99% CI 0.35-0.75, and
      0.63, 99% CI 0.51-0.79; both p<0.0001). For stroke, the reduction in risk in
      participants with 5-year risk of major vascular events lower than 10% (RR per 1.0
      mmol/L LDL cholesterol reduction 0.76, 99% CI 0.61-0.95, p=0.0012) was also
      similar to that seen in higher risk categories (trend p=0.3). In participants
      without a history of vascular disease, statins reduced the risks of vascular (RR
      per 1.0 mmol/L LDL cholesterol reduction 0.85, 95% CI 0.77-0.95) and all-cause
      mortality (RR 0.91, 95% CI 0.85-0.97), and the proportional reductions were
      similar by baseline risk. There was no evidence that reduction of LDL cholesterol
      with a statin increased cancer incidence (RR per 1.0 mmol/L LDL cholesterol
      reduction 1.00, 95% CI 0.96-1.04), cancer mortality (RR 0.99, 95% CI 0.93-1.06),
      or other non-vascular mortality. INTERPRETATION: In individuals with 5-year risk
      of major vascular events lower than 10%, each 1 mmol/L reduction in LDL
      cholesterol produced an absolute reduction in major vascular events of about 11
      per 1000 over 5 years. This benefit greatly exceeds any known hazards of statin
      therapy. Under present guidelines, such individuals would not typically be
      regarded as suitable for LDL-lowering statin therapy. The present report
      suggests, therefore, that these guidelines might need to be reconsidered.
      FUNDING: British Heart Foundation; UK Medical Research Council; Cancer Research
      UK; European Community Biomed Programme; Australian National Health and Medical
      Research Council; National Heart Foundation, Australia.

PMID- 22607826
TI  - WITHDRAWN: NBTS 2012 abstracts.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 22607827
TI  - Wild boars as hosts of human-pathogenic Anaplasma phagocytophilum variants.
AB  - To investigate the potential of wild boars to host Anaplasma phagocytophilum, we
      analyzed bacterial 16S rRNA and ank genes. DNA sequencing identified several A.
      phagocytophilum variants, including a predominance of strains known to cause
      human disease. Boars are thus hosts for A. phagocytophilum, notably, strains
      associated with human granulocytic anaplasmosis.

PMID- 22607825
TI  - Plasma HDL cholesterol and risk of myocardial infarction: a mendelian
      randomisation study.
AB  - BACKGROUND: High plasma HDL cholesterol is associated with reduced risk of
      myocardial infarction, but whether this association is causal is unclear.
      Exploiting the fact that genotypes are randomly assigned at meiosis, are
      independent of non-genetic confounding, and are unmodified by disease processes,
      mendelian randomisation can be used to test the hypothesis that the association
      of a plasma biomarker with disease is causal. METHODS: We performed two mendelian
      randomisation analyses. First, we used as an instrument a single nucleotide
      polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser) and tested
      this SNP in 20 studies (20,913 myocardial infarction cases, 95,407 controls).
      Second, we used as an instrument a genetic score consisting of 14 common SNPs
      that exclusively associate with HDL cholesterol and tested this score in up to
      12,482 cases of myocardial infarction and 41,331 controls. As a positive control,
      we also tested a genetic score of 13 common SNPs exclusively associated with LDL
      cholesterol. FINDINGS: Carriers of the LIPG 396Ser allele (2.6% frequency) had
      higher HDL cholesterol (0.14 mmol/L higher, p=8*10(-13)) but similar levels of
      other lipid and non-lipid risk factors for myocardial infarction compared with
      non-carriers. This difference in HDL cholesterol is expected to decrease risk of
      myocardial infarction by 13% (odds ratio [OR] 0.87, 95% CI 0.84-0.91). However,
      we noted that the 396Ser allele was not associated with risk of myocardial
      infarction (OR 0.99, 95% CI 0.88-1.11, p=0.85). From observational epidemiology,
      an increase of 1 SD in HDL cholesterol was associated with reduced risk of
      myocardial infarction (OR 0.62, 95% CI 0.58-0.66). However, a 1 SD increase in
      HDL cholesterol due to genetic score was not associated with risk of myocardial
      infarction (OR 0.93, 95% CI 0.68-1.26, p=0.63). For LDL cholesterol, the estimate
      from observational epidemiology (a 1 SD increase in LDL cholesterol associated
      with OR 1.54, 95% CI 1.45-1.63) was concordant with that from genetic score (OR
      2.13, 95% CI 1.69-2.69, p=2*10(-10)). INTERPRETATION: Some genetic mechanisms
      that raise plasma HDL cholesterol do not seem to lower risk of myocardial
      infarction. These data challenge the concept that raising of plasma HDL
      cholesterol will uniformly translate into reductions in risk of myocardial
      infarction. FUNDING: US National Institutes of Health, The Wellcome Trust,
      European Union, British Heart Foundation, and the German Federal Ministry of
      Education and Research.

PMID- 22607829
TI  - Inhibitory effect of synovial fluid on tendon-to-bone healing: an experimental
      study in rabbits.
AB  - PURPOSE: The purpose of this study was to explore the effects of joint synovial
      fluid on tendon-to-bone healing in intra-articular ligament reconstruction of the
      knee. METHODS: We divided 40 female New Zealand white rabbits into 4 groups
      randomly, with 10 animals in each group. Transfer of the semitendinosus tendon to
      the tibial bone tunnel was performed to create tendon-to-bone healing models. An
      intra-articular bone tunnel (IBT) was used on the left side and an extra
      articular bone tunnel (EBT) on the right. Histologic evaluation was performed at
      2, 4, and 8 weeks after the operation and biomechanical testing at 8 weeks.
      RESULTS: On the basis of fibroblast proliferation, collagen fiber density,
      collagen fiber orientation, and tendon-to-bone connection, histologic scores were
      significantly lower in the IBT group than in the EBT group at 2, 4, and 8 weeks.
      Cell counts per high-power field at the tendon-bone interface were significantly
      lower in the IBT group than in the EBT group at 2 and 4 weeks. In addition,
      biomechanical testing showed that the IBT group was significantly inferior to the
      EBT group in terms of ultimate failure load, yield load, and stiffness. There was
      also a significant difference between the 2 groups in failure mode. CONCLUSIONS:
      Joint synovial fluid appeared to have an inhibitory effect on tendon-to-bone
      healing in rabbits at an early stage. CLINICAL RELEVANCE: Our findings imply that
      prevention of infiltration of joint synovial fluid into the bone tunnel might be
      beneficial in improving the clinical outcome of cruciate ligament reconstruction
      of the knee.

PMID- 22607828
TI  - Outcomes of arthroscopic and open surgical repair of isolated subscapularis
      tendon tears.
AB  - PURPOSE: Reports of the results of subscapularis repairs make up a very small
      minority of the published literature on rotator cuff repairs, yet subscapularis
      tears cause significant pain and dysfunction for patients. The goals of this
      study were to systematically review the published results after subscapularis
      repair and to compare arthroscopic versus open techniques when appropriate.
      METHODS: The Cochrane, PubMed, and Embase databases were reviewed for studies
      evaluating isolated subscapularis repairs. If a study reported outcomes for both
      subscapularis and supraspinatus tears, a subgroup analysis of isolated
      subscapularis tears was necessary for inclusion in this review. Other inclusion
      criteria included a minimum of 1-year follow-up. RESULTS: We found 3 arthroscopic
      repair studies and 6 open repair studies that met all inclusion criteria. The
      mean patient age was 49.2 years, and the mean time from injury to surgical repair
      was 11.1 months. Constant scores were consistent between groups, with a mean
      postoperative score of 88.1. Pain scores improved significantly after repair,
      with a mean of 13.4 (on a scale ranging from 0 to 15, with 15 being no pain) in
      the arthroscopic repair group and 11.5 in the open repair group. Concomitant
      procedures were common, with biceps tenodesis being the most common, having been
      performed in 54.8% of shoulders, followed by biceps tenotomy and biceps
      recentering. Healing was reported in 90% to 95% of shoulders. CONCLUSIONS:
      Subscapularis tears can cause significant morbidity and often occur as traumatic
      injury in a younger population. Pain and function can be restored with repair,
      with excellent healing rates. The characteristic injury pattern suggested by a
      review of the literature is 1 where such tears are full thickness yet involve a
      portion of the tendon in the craniocaudal dimension. Concomitant procedures are
      common and can affect the results, because biceps tenotomy and tenodesis have
      been shown to significantly improve pain as well. All studies were Level IV,
      which introduced selection bias. LEVEL OF EVIDENCE: Level IV, systematic review
      of Level IV studies.

PMID- 22607831
TI  - Synovial sarcoma of the infratemporal fossa with extension into the oral cavity-
      a rare presentation and literature review.

PMID- 22607830
TI  - Biomechanical analysis of suture bridge fixation for tibial eminence fractures.
AB  - PURPOSE: To perform a biomechanical analysis of suture bridge fixation for tibial
      eminence fractures using PushLock anchors (Arthrex, Naples, FL) and compare it
      with traditional suture fixation and screw fixation. METHODS: This study used 24
      porcine knees, divided into 3 comparison fixation groups: PushLock suture bridge
      fixation, screw fixation, and suture fixation. Each knee was dissected of all
      soft tissue, leaving only the anterior cruciate ligament. A tibial eminence
      fracture was created with disruption of the posterior hinge, and each knee was
      fixed with a randomly assigned fixation technique. After fixation, each knee
      underwent 2 phases of biomechanical testing. The initial cyclic dynamic phase
      assessed the displacement change after 200 cycles (in millimeters) and initial
      stiffness (in Newtons per millimeter) of the fixation construct. After completion
      of dynamic testing, each specimen underwent a single tensile failure test load to
      assess ultimate failure load (in Newtons) and displacement (in millimeters) to
      ultimate failure. RESULTS: There was a significant difference for the load-to
      failure outcome variable among treatment groups (P = .004 by analysis of
      variance, 1 - beta = 0.851). Mean ultimate failure load borne by the PushLock
      fixation group was statistically significantly higher in comparison with the
      screw (P = .007) and suture (P = .017) fixation groups. For the cyclical testing,
      the primary outcome variable of displacement change after 200 loading cycles
      failed to show a significant difference among the 3 groups (P = .412).
      CONCLUSIONS: Suture bridge fixation with PushLock anchors is a new and effective
      surgical technique for the treatment of displaced tibial eminence fractures. By
      use of a high-bone density animal model, our results suggest that this suture
      bridge construct provides superior fixation with regard to ultimate failure load
      compared with standard screw fixation and suture fixation. CLINICAL RELEVANCE:
      The suture bridge technique provides another fixation option for displaced tibial
      eminence fractures with comparable, and in some instances superior, biomechanical
      properties to screw fixation and suture fixation.

PMID- 22607832
TI  - Staged treatment of temporomandibular joint ankylosis with micrognathia using
      mandibular osteodistraction and advancement genioplasty.
AB  - PURPOSE: Distraction osteogenesis can be used to correct micrognathia after
      temporomandibular joint (TMJ) ankylosis. However, there is still some controversy
      over the proper sequencing of management for the ankylosed patients. The
      objective of the present study was to evaluate a staged treatment of TMJ
      ankylosis accompanied by micrognathia using arthroplasty, mandibular distraction
      osteogenesis, and advancement genioplasty. PATIENTS AND METHODS: A total of 12
      bilateral TMJ ankylosis patients with micrognathia (aged 17 to 27 years)
      underwent arthroplasty as the initial surgical procedure, followed by orthodontic
      treatment and correction of mandibular micrognathia by osteodistraction and
      advancement genioplasty as the second surgical procedure. The clinical results
      were evaluated by mouth opening, radiography, medical photography, and
      respiratory function. RESULTS: The patients were followed up for a minimum of 8
      months to a maximum of 36 months. The TMJ ankylosis was released successfully in
      all the patients, showing an increase in average mouth opening from 3.3 mm
      preoperatively to 35.8 mm postoperatively. Micrognathia was corrected, and,
      remarkably, the obstructive sleep apnea and hypopnea syndrome was cured.
      Satisfactory occlusion was achieved with orthodontic treatment. CONCLUSIONS: Our
      data suggest that a staged and surgical orthodontic treatment might be a better
      approach to manage TMJ ankylosis accompanied by mandibular hypoplasia. In
      addition to mandibular osteodistraction, advancement genioplasty should be
      considered for better improvement in facial esthetics and respiratory function.

PMID- 22607833
TI  - Successful reconstruction of nongrowing hemifacial microsomia patients with
      unilateral temporomandibular joint total joint prosthesis and orthognathic
      surgery.
AB  - PURPOSE: Traditionally, patients with hemifacial microsomia (HFM) and significant
      ipsilateral hypoplasia or absence of the condyle and ramus undergo reconstruction
      on the ipsilateral side with autogenous tissues such as rib grafts, often with
      compromised results. This study analyzed the surgical treatment outcomes of
      nongrowing patients with HFM and reconstruction of the ipsilateral
      temporomandibular joint (TMJ) and advancement of the mandible with a patient
      fitted TMJ total joint prosthesis (TMJ Concepts, Inc, Ventura, CA), a
      contralateral mandibular ramus sagittal split osteotomy, and maxillary
      osteotomies performed in 1 operation. PATIENTS AND METHODS: All nongrowing
      patients with HFM treated with this surgical protocol from 1997 to 2010 in a
      single private practice were included in this study and subjectively evaluated
      before surgery and at the longest postsurgical follow-up for pain, diet, jaw
      function, and disability using a visual numerical scale (0 to 10). Surgical
      changes and postsurgical stability were analyzed using lateral cephalograms
      before surgery, immediately after surgery, and at the longest follow-up. RESULTS:
      Six patients (4 female and 2 male) were included in this study, with an average
      age at surgery of 23.5 years (range, 14 to 39 yrs) and an average follow-up of 6
      years 3 months (range, 1 yr to 11 yrs 4 mo). For all subjective parameters, all
      patients improved or remained the same. Incisal opening improved or remained the
      same in 4 of the 6 patients, with 2 patients having decreased opening. Excursive
      movements decreased. The maxillomandibular complex was surgically rotated
      counterclockwise, advanced, and transversely leveled, with the anterior maxillary
      reference points (anterior nasal spine, point A) undergoing relative small
      movements. The mandibular incisor tips (lower incisor tips) advanced a mean of
      8.9 mm, point B 14.8 mm, pogonion 18.6 mm, menton 17.5 mm and the occlusal plane
      angle decreased -12.3 degrees . Postsurgical long-term stability indicated that
      the anterior maxillary references changed a significant amount, whereas all
      horizontal and vertical anterior mandibular measurements (lower incisor tip,
      point B, pogonion, menton) and the occlusal plane showed no significant changes.
      CONCLUSIONS: The TMJ Concepts total joint prosthesis in conjunction with
      orthognathic surgery for TMJ and jaw reconstruction in nongrowing patients with
      HFM is highly predictable for skeletal and occlusal stability, comfort, TMJ
      function, and improved facial balance.

PMID- 22607834
TI  - The economic costs of pain in the United States.
AB  - In 2008, according to the Medical Expenditure Panel Survey (MEPS), about 100
      million adults in the United States were affected by chronic pain, including
      joint pain or arthritis. Pain is costly to the nation because it requires medical
      treatment and complicates treatment for other ailments. Also, pain lowers worker
      productivity. Using the 2008 MEPS, we estimated 1) the portion of total U.S.
      health care costs attributable to pain; and 2) the annual costs of pain
      associated with lower worker productivity. We found that the total costs ranged
      from $560 to $635 billion in 2010 dollars. The additional health care costs due
      to pain ranged from $261 to $300 billion. This represents an increase in annual
      per person health care costs ranging from $261 to $300 compared to a base of
      about $4,250 for persons without pain. The value of lost productivity due to pain
      ranged from $299 to $335 billion. We found that the annual cost of pain was
      greater than the annual costs of heart disease ($309 billion), cancer ($243
      billion), and diabetes ($188 billion). Our estimates are conservative because
      they do not include costs associated with pain for nursing home residents,
      children, military personnel, and persons who are incarcerated. PERSPECTIVE: This
      study estimates that the national cost of pain ranges from $560 to $635 billion,
      larger than the cost of the nation's priority health conditions. Because of its
      economic toll on society, the nation should invest in research, education, and
      training to advocate the successful treatment, management, and prevention of
      pain.

PMID- 22607835
TI  - Idiopathic accelerated gastric emptying presenting in adults with post-prandial
      diarrhea and reactive hypoglycemia: a case series.
AB  - INTRODUCTION: We have previously reported the association of gastrointestinal and
      hypoglycemic symptoms, with idiopathic accelerated gastric emptying. We now
      report the first series of six similar cases. CASE PRESENTATIONS: Patient 1: A 24
      year-old Caucasian man presented to our facility with a six-month history of post
      prandial nausea, flatulence, bloating, abdominal discomfort and associated
      diarrhea. He had associated episodes of fatigue, sweating, anxiety, confusion and
      craving for sweet foods. Patient 2: A 52-year-old Caucasian woman presented to
      our facility with a 15-year history of post-prandial bloating, abdominal pain and
      diarrhea, often associated with nausea, severe sweating, and fatigue. Patient 3:
      An 18-year-old Caucasian woman presented to our facility with a nine-year history
      of post-prandial diarrhea, abdominal bloating and pain. There was associated
      nausea, tremor, lethargy, and craving for sweet foods. Patient 4: A 77-year-old
      Caucasian woman presented to our facility with a four-month history of epigastric
      distension, pain after eating and a change in bowel habit. She experienced
      intermittent severe diarrhea and marked fatigue, nausea and sweating. Patient 5:
      A 23-year-old Caucasian woman presented to our facility with a two-year history
      of early satiety, and diarrhea after eating. She also complained of feeling faint
      and weak between meals, when she became cold and clammy, and on several occasions
      lost consciousness during these episodes. Patient 6: A 64-year-old Caucasian
      woman presented to our facility with a 10-year history of nausea, early satiety
      and profound bloating followed by diarrhea. All symptoms predominantly occurred
      in the first three hours after eating, when she felt faint, lethargic, and had a
      craving for sweet foods. In all cases, symptoms were alleviated or resolved by
      taking sweet food or drink and response to treatment was 90% or greater in all
      cases. CONCLUSIONS: This series extends our description of this new clinical
      syndrome. All patients responded well to treatment for accelerated gastric
      emptying. Clinicians in the disciplines of endocrinology, gastroenterology,
      neurology and general practice are likely to find this information useful as they
      will consult patients with some or all of these symptoms and in a proportion of
      these patients idiopathic accelerated gastric emptying may be present and provide
      a useful avenue for therapeutic intervention.

PMID- 22607836
TI  - MASP interactions with plasma-derived MBL.
AB  - The interaction of mannan-binding lectin (MBL) with its associated serine
      proteases (MASPs) was investigated using recombinant (r) MBL, plasma-derived (pd)
      MBL, rMASP-3 and rMAp19. When mixed with MBL-deficient serum, rMBL and pdMBL
      associated with free MASP-2 to (re)gain complement-activating activity. MASPs
      already associated with pdMBL did not exchange with rMASP-3 or rMAp19, which
      bound to non-overlapping sites on MBL. Thus, rMASP-3 and rMAp19 bound to free
      available sites on rMBL and pdMBL. These results have important implications for
      the therapeutic use of MBL preparations.

PMID- 22607837
TI  - Description and analysis of hand forces in medicine cart pushing tasks.
AB  - The primary objectives of this study were to describe and analyze the hand force
      exertion patterns of experienced nursing home nurses and nursing students during
      dynamic medicine cart pushing tasks in Initial, Sustained, Turning, and Stopping
      motion phases. A 2 * 2 * 2 factorial experiment was conducted with 22
      participants to estimate the effects of lane congestion, precision cart control,
      and floor surface on horizontal hand forces. Root mean squared (RMS) lane
      deviation patterns were also described to provide an indicator of cart handling
      difficulty across the different study conditions. Descriptive statistics revealed
      that nurses exerted greater mean hand force (10%) and made more (12%) lane
      deviation than students and that the highest two-hand forces of 147N were
      measured in the Turning phase on carpet. Strong correlations between work
      experience group, body mass, and BMI required that force data for nurses and
      students be collapsed in analytical models where no group differences existed.
      Predicted pushing forces on carpeted floor surface were significantly greater
      than on tile in Initial (14N), Sustained (14N) and Turning (18N), except in
      stopping where pulling forces were 37N lower. High lane congestion predicted
      significant peak force increases of 4N and 7N in Sustained and Turning,
      respectively, but decreased by 20N in Initial. High precision control led to
      significant decreases in two-hand forces that ranged from 4 to 20N across motion
      phases. Complex interactions among the experimental factors suggest that work
      environment (lane congestion and floor surface) and work demands (precision
      control) should be included in the evaluation of pushing tasks and considered
      prior to making renovations to nursing home environments.

PMID- 22607838
TI  - Wrist postures in the general population of computer users during a computer
      task.
AB  - Computer activities have commonly been linked to the development of
      musculoskeletal disorders (MSDs) in the upper limbs. However, to understand the
      effects computer use has on such disorders, it is necessary to identify and
      classify the movements involved in performing common computer tasks, one of these
      being typing. Motion analysis techniques were adopted to determine the movements
      involved during a typing task. This involved markers being placed on the
      knuckles, wrists and forearms of participants. This marker configuration allowed
      for the flexion, extension, radial deviation, ulnar deviation and a combination
      of these movements to be calculated. The results in one plane of motion show a
      mean extension|flexion and radial|ulnar deviation of 18.825 degrees  +/- 10.013
      degrees  and 5.228 degrees  +/- 11.703 degrees  respectively. The most common
      position in two planes of motion was 20 degrees  extension with a simultaneous 20
      degrees  ulnar deviation (10.72%). The results depict an alternative method of
      categorizing wrist positions in two planes during computer use. Coincident wrist
      postures should be addressed as opposed to motion in a single plane as these
      postures may result in different ergonomic risk factors developing.

PMID- 22607839
TI  - [A man with a painful wrist after a fall].
AB  - A 67-year-old man presented in the emergency department after a fall on his
      outstretched right hand. Physical examination showed tenderness of the anatomical
      snuffbox and the dorsal side of the wrist. X-rays of the wrist revealed a
      perilunate luxation combined with a scaphoid fracture.

PMID- 22607840
TI  - [Medical and biological consequences of nuclear disasters].
AB  - Medical risks of radiation exaggerated; psychological risks underestimated. The
      discussion about atomic energy has become topical again following the nuclear
      accident in Fukushima. There is some argument about the gravity of medical and
      biological consequences of prolonged exposure to radiation. The risk of cancer
      following a low dose of radiation is usually estimated by linear extrapolation of
      the incidence of cancer among survivors of the atomic bombs dropped on Hiroshima
      and Nagasaki in 1945. The radiobiological linear-quadratic model (LQ-model) gives
      a more accurate description of observed data, is radiobiologically more plausible
      and is better supported by experimental and clinical data. On the basis of this
      model there is less risk of cancer being induced following radiation exposure.
      The gravest consequence of Chernobyl and Fukushima is not the medical and
      biological damage, but the psychological and economical impact on rescue workers
      and former inhabitants.

PMID- 22607841
TI  - [Embolisation in spontaneous haemopneumothorax].
AB  - BACKGROUND: Spontaneous haemopneumothorax is a rare disorder and is defined as
      spontaneous pneumothorax associated with the accumulation of more than 400 ml of
      blood in the pleural cavity. CASE DESCRIPTION: A 32-year-old male presented at
      the emergency department following sudden onset of right-sided stinging chest
      pain and difficulty in breathing. The chest X-ray showed right-sided
      hydropneumothorax. A tube thoracostomy was performed, which immediately drained
      1500 ml of sanguinolent fluid. The first CT-scan showed no active bleeding.
      Several hours later the patient became haemodynamically unstable and an
      additional CT-angiogram was performed. This revealed an extravasation in the area
      of the second posterior intercostal artery, which was successfully embolised
      subsequently. This resulted in a haemodynamically stable patient, allowing
      elective video-assisted thoracic surgery. CONCLUSION: Spontaneous
      haemopneumothorax is a life-threatening disorder. After initial drainage video
      assisted thoracic surgery is to be preferred to conservative treatment or
      thoracotomy. However, it is necessary for the patient to be haemodynamically
      stable. In this case intervention radiology contributed to a minimally invasive
      approach. This therefore also merits consideration as a therapeutic option.

PMID- 22607842
TI  - [Endocarditis caused by rare Gram-positive bacteria: investigate for
      gastrointestinal disorders].
AB  - Gemella haemolysans, Streptococcus equinus and Tropheryma whipplei are rare Gram
      positive bacteria which may cause endocarditis and are associated with
      gastrointestinal disorders. We report on three patients with infective
      endocarditis caused by these microorganisms. G. haemolysans and S. equinus
      (Streptococcus bovis group) were isolated from blood cultures, and T. whipplei
      was diagnosed by molecular typing of an excised heart valve. The association
      between endocarditis caused by these microorganisms and gastrointestinal
      disorders warranted further examination. Endoscopic examination revealed a
      colonic carcinoma in the patient with G. haemolysans endocarditis and
      diverticulosis in the patient with S. equinus endocarditis. No gastrointestinal
      tract disorders were found in the patient with T. whipplei endocarditis, but this
      does not exclude Whipple's disease. Examination of the gastrointestinal tract for
      a focus of infection should be considered in patients with endocarditis caused by
      G. haemolysans, S. equinus and T. whipplei if no other source of bacteraemia is
      apparent.

PMID- 22607845
TI  - Offshore experiments on styrene spillage in marine waters for risk assessment.
AB  - Within the context of risk evaluation of chemical spillages into the marine
      environment, this paper reports on an offshore experiment to study the behaviour
      of styrene spilled into sea under natural conditions and discusses theoretical
      approaches. Floating structures were used to enclose the spillage and the gaseous
      cloud formation, and dissolution processes were in situ monitored. The
      identification of spill risks for man and marine environment through GESAMP's
      hazard profile is described for styrene: Styrene is rated as a chemical with a
      significant health hazard that will float but also evaporate. However, monitoring
      of the water column in the experiments showed that the concentration of styrene
      in water during the first hour represents 50% of the product spilled. For the
      potentially exposed public, the GESAMP hazard rating recommends the closure of
      beaches and evacuation. The risk assessment developed from experimental data
      confirms this safety advice.

PMID- 22607846
TI  - Biosecurity risks associated with in-water and shore-based marine vessel hull
      cleaning operations.
AB  - The removal of biofouling from vessels during hull cleaning can pose a
      biosecurity threat if viable, non-indigenous organisms are released into the
      aquatic environment. However, the effect of cleaning on biofouling organism
      viability in different types of cleaning operations has been poorly studied. We
      compared the effects of hull cleaning on biofouling organisms removed from 36
      marine vessels during in-water (without capture of cleaning waste) and shore
      based (with capture, and treatment of cleaning waste) cleaning. In-water cleaning
      resulted in higher proportions of viable biofouling organisms surviving cleaning
      (62.3 +/- 7.1% of all organisms examined) compared to dry dock (37.8 +/- 8.6%)
      and haul-out (20.1 +/- 5.3%) operations. For shore-based facilities with effluent
      treatment systems, concentrations of organisms and/or their propagules in
      cleaning effluent was reduced by >= 98.5% compared to initial hydro-blast
      effluent concentrations. These results can be used in guidance for hull cleaning
      operations to minimize associated biosecurity risk.

PMID- 22607847
TI  - Taxonomic distinctness in Mediterranean marine nematodes and its relevance for
      environmental impact assessment.
AB  - Taxonomic distinctness has been applied successfully for the exploration of
      biodiversity patterns, yet its relevance in environmental impact assessment is
      far from being unquestioned. In this study, we assessed the potential of
      taxonomic distinctness to discern perturbed and unperturbed sites by analysing
      Mediterranean nematode assemblages. Geographic and habitat-related effects on the
      performance of the index were also explored. Above all, our findings do not
      corroborate the conjecture that taxonomic distinctness could be largely
      unaffected by natural variability, habitat features, and biogeographic context,
      casting doubts on potential generalization concerning its application as an
      indicator of environmental stress. Taxonomic distinctness represents an excellent
      metric to identifying taxonomic properties of ecological systems but, as for
      other ecological indices, it should be viewed as a complementary tool in
      environmental impact assessment, due to its sensitiveness to specific
      environmental features of systems being investigated.

PMID- 22607848
TI  - Evaluation of bacteriological and nutrient concerns in nearshore waters of a
      barrier island community in SW Florida.
AB  - To determine if local onsite treatment systems affect nearshore water quality,
      seasonal and rain event monitoring of bacteria and nitrogen was conducted on the
      Gulf and estuary sides of Captiva Island. Monitoring wells were used to examine
      the relationship between surface water and groundwater quality. Nitrates were
      found to be significantly greater in ground water samples from the areas of
      Captiva using onsite treatment compared to areas with sewer. However, groundwater
      enterococci were no greater in areas with onsite treatment. Surface water
      nitrogen was significantly greater near onsite systems than areas with sewer,
      linking groundwater and surface water quality. Surface water enterococci
      increased significantly after rain events. Study results indicated stormwater
      runoff disperses indicator bacteria from diffuse terrestrial sources into
      nearshore waters, elevating the concentrations. This study reveals local onsite
      treatment systems produce elevated surface water nitrogen levels but do not
      contribute to elevated indicator bacteria concentrations in this system.

PMID- 22607849
TI  - GENESIS-PRAXY (GENdEr and Sex determInantS of cardiovascular disease: From bench
      to beyond-Premature Acute Coronary SYndrome).
AB  - BACKGROUND: Previous research has not adequately addressed the topic of sex and
      gender differences in occurrence of premature acute coronary syndrome (ACS). This
      study will investigate the clinical presentation, prognosis, and health care use
      in young men and women with ACS. METHODS: We have set up a prospective,
      multicenter study of 1,576 patients aged 18-55 years and admitted to hospital
      with ACS. At baseline, questionnaires will be administered, and anthropometric
      and biological measurements will be performed. The patients will be observed for
      at least 1 year, with additional questionnaires being administered at 1, 6, and
      12 months post-discharge. A review of medical records will be performed both at
      baseline and during follow-up. CONCLUSIONS: This study will provide important
      evidence on the roles that a wide range of behavioral, environmental, and
      biological factors play in premature ACS and will help determine to what extent
      these roles depend on the individual's sex and gender. Ultimately, the knowledge
      derived from this study may facilitate accurate diagnosis and effective
      prevention and management of ACS in young women and men.

PMID- 22607850
TI  - A novel algorithm for individualized cardiac resynchronization therapy: rationale
      and design of the adaptive cardiac resynchronization therapy trial.
AB  - BACKGROUND: The magnitude of benefit of cardiac resynchronization therapy (CRT)
      varies significantly among its recipients; approximately 30% of CRT patients do
      not report clinical improvement. Optimization of CRT pacing parameters can
      further improve cardiac function, both acutely and chronically. Echocardiographic
      optimization is used in clinical practice, but it is time and resource consuming.
      In addition, optimal settings at rest may change later with activity or cardiac
      remodeling. The adaptive CRT (aCRT) algorithm was designed to provide automatic
      ambulatory adjustment of CRT pacing configuration (left ventricular or
      biventricular pacing) and device delays based on periodic measurement of
      electrical conduction intervals. METHODS: The aCRT algorithm is currently
      undergoing evaluation in a prospective, randomized, double-blinded, worldwide
      clinical trial. The trial enrolled 522 patients, who satisfied standard clinical
      indications for a CRT device. Within 2 weeks after the implant, the patients were
      randomized to aCRT versus echo-optimized biventricular pacing (Echo) settings in
      2:1 ratio and followed up at 1-, 3-, 6-, and 12-month postrandomization. The
      noninferiority primary trial objectives at 6-month postrandomization are to
      demonstrate that (a) the percentage of aCRT patients who improved in their
      clinical composite score is at least as high as the percentage of Echo patients;
      (b) cardiac performance as assessed by echocardiography is similar when using
      aCRT settings versus echo-optimized settings; and (c) aCRT does not result in
      inappropriate device settings. First and last patient enrollments occurred in
      November 2009 and December 2010, respectively. CONCLUSIONS: The safety and
      efficacy of the aCRT algorithm will be evaluated in this ongoing clinical trial.

PMID- 22607851
TI  - Rationale and design of the PRAETORIAN trial: a Prospective, RAndomizEd
      comparison of subcuTaneOus and tRansvenous ImplANtable cardioverter-defibrillator
      therapy.
AB  - BACKGROUND: Implantable cardioverter-defibrillators (ICDs) are widely used to
      prevent fatal outcomes associated with life-threatening arrhythmic episodes in a
      variety of cardiac diseases. These ICDs rely on transvenous leads for cardiac
      sensing and defibrillation. A new entirely subcutaneous ICD overcomes problems
      associated with transvenous leads. However, the role of the subcutaneous ICD as
      an adjunctive or primary therapy in patients at risk for sudden cardiac death is
      unclear. STUDY DESIGN: The PRAETORIAN trial is an investigator-initiated,
      randomized, controlled, multicenter, prospective 2-arm trial that outlines the
      advantages and disadvantages of the subcutaneous ICD. Patients with a class I or
      IIa indication for ICD therapy without an indication for bradypacing or
      tachypacing are included. A total of 700 patients are randomized to either the
      subcutaneous or transvenous ICD (1:1). The study is powered to claim
      noninferiority of the subcutaneous ICD with respect to the composite primary
      endpoint of inappropriate shocks and ICD-related complications. After
      noninferiority is established, statistical analysis is done for potential
      superiority. Secondary endpoint comparisons of shock efficacy and patient
      mortality are also made. CONCLUSION: The PRAETORIAN trial is a randomized trial
      that aims to gain scientific evidence for the use of the subcutaneous ICD
      compared with the transvenous ICD in a population of patients with conventional
      ICD with respect to major ICD-related adverse events. This trial is registered at
      ClinicalTrials.gov with trial ID NCT01296022.

PMID- 22607852
TI  - Rationale and design of a randomized study to determine the value of central
      Blood Pressure for GUIDing managEment of hypertension: the BP GUIDE study.
AB  - BACKGROUND: Noninvasive estimates of central blood pressure (BP) predict
      cardiovascular morbidity and mortality independent of brachial BP. However, there
      are limited data on the usefulness of central BP in clinical practice. This study
      aims to test the value of central BP as a management tool for physicians treating
      patients with essential hypertension. METHODS: Participants with uncomplicated
      essential hypertension (N = 284) will be randomized to 12 months of treatment
      decisions guided by usual care (based on office, home, and 24-hour ambulatory
      brachial BP) or, in addition, by central BP estimated using radial tonometry
      (based on age- and sex-specific normal central systolic BP values).
      Recommendations regarding titration of antihypertensive medication (increase,
      decrease, or maintain dose) will be provided to each participant's general
      practitioner as well as the participant themselves. Relevant clinical information
      (eg, comorbidities, left ventricular [LV] mass, blood biochemistry, and BP
      related symptoms) will be considered when making titration recommendations in all
      participants. The primary outcome measures will be (1) change in LV mass (by real
      time 3-dimensional echocardiography), (2) amount of medication used, and (3)
      quality of life. Analysis will be by intention to treat. CONCLUSIONS: It is
      expected that there will be no significant difference in LV mass between groups.
      However, it is hypothesized that there will be significantly reduced use of
      medication and improved quality of life in the central BP group because more
      appropriate titration choices will be made to maintain normal central systolic
      BP. Results are expected in 2012.

PMID- 22607853
TI  - Rationale and design of the Cangrelor versus standard therapy to acHieve optimal
      Management of Platelet InhibitiON PHOENIX trial.
AB  - BACKGROUND: Despite robust efficacy in the reduction of ischemic events in
      patients who require percutaneous coronary intervention (PCI), current P2Y(12)
      inhibitors have limitations. In particular, they require hours to be effective,
      and they can only be administered orally. Cangrelor is an intravenous, potent,
      and reversible P2Y(12) inhibitor with fast onset and offset of action. We
      designed CHAMPION PHOENIX to evaluate the efficacy and safety of cangrelor in
      patients with atherosclerosis undergoing PCI. TRIAL DESIGN: The CHAMPION PHOENIX
      is a randomized, double-blind, double-dummy, superiority trial comparing
      cangrelor with clopidogrel standard of care in approximately 10,900 patients who
      have not previously received a P2Y(12) inhibitor and who require PCI, including
      patients with stable angina and with acute coronary syndromes (with or without ST
      segment elevation). The primary objective of the study is to demonstrate that
      cangrelor will reduce the incidence of the composite of death, myocardial
      infarction (MI), ischemia-driven revascularization, or stent thrombosis in the 48
      hours after randomization compared with clopidogrel without excessive
      periprocedural bleeding. The key secondary objective is to demonstrate that
      cangrelor will reduce the incidence of stent thrombosis. Myocardial infarction
      will be defined according to the universal MI definition, adapting the definition
      of PCI-related (type 4a) MI. Bleeding will be assessed according to the
      thrombolysis in myocardial infarction, GUSTO, and Bleeding Academic Research
      Consortium (BARC) scales. CONCLUSION: The CHAMPION PHOENIX may establish the role
      of cangrelor in the care of patients who require PCI across the spectrum of
      stable and unstable coronary diseases in the setting of current treatment
      strategies.

PMID- 22607854
TI  - Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for
      treatment of ischemic heart disease: Future research needs prioritization.
AB  - BACKGROUND: A recent review evaluated the comparative effectiveness of
      angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin II receptor
      blockers (ARBs) in patients with or at high risk for stable ischemic heart
      disease (IHD). The prioritization of future research needs has customarily been
      an informal process that is not responsive to the needs of all relevant
      stakeholders. METHODS: As part of the Agency for Healthcare Research and Quality
      Effective Healthcare Program, the Duke Evidence-Based Practice Center engaged a
      diverse stakeholder group in 3 exercises designed to prioritize future research
      needs pertaining to the comparative effectiveness of ACE-I/ARB in patients with
      stable IHD. RESULTS: Our stakeholders prioritized the following areas of research
      pertaining to the comparative effectiveness of ACE-I/ARB in stable IHD: (1)
      strategies to enhance greater evidence-based use, (2) impact of adherence on
      effectiveness or harms, (3) impact of comorbidities on effectiveness or harms,
      (4) medication impact on patient quality of life, (5) impact of demographic
      differences on effectiveness or harms, and (6) medication impact on incidence of
      new diagnoses. This project also yielded suggestions regarding potential study
      designs to address these future research needs. CONCLUSIONS: Our stakeholders
      prioritized research designed to facilitate (1) tailored ACE-I/ARB treatment
      based on individual patient characteristics and (2) implementation of ACE-I/ARB
      use among patients most likely to benefit. With respect to suggested study
      designs, it was felt that analysis of existing data would sufficiently address
      many of the top-tier future research needs (FRNs).

PMID- 22607855
TI  - Multiple biomarkers at admission are associated with angiographic,
      electrocardiographic, and imaging cardiovascular mechanistic markers of outcomes
      in patients undergoing primary percutaneous coronary intervention for acute ST
      elevation myocardial infarction.
AB  - BACKGROUND: The multimarker risk score, based on estimated glomerular filtration
      rate, glucose, and N-terminal probrain natriuretic peptide (NT-proBNP), has been
      shown to predict mortality in patients with ST-segment elevation myocardial
      infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI).
      In this study, we investigated the relation between the multimarker risk score
      and cardiovascular mechanistic markers of outcomes in STEMI patients undergoing
      PPCI. METHODS: Complete biomarkers were available in 197 patients with STEMI.
      Angiographic Thrombolysis In Myocardial Infarction flow grade and myocardial
      blush grade at the end of the PPCI, electrocardiographic ST-segment resolution
      (STR) at the time of last contrast injection and 240 minutes after last contrast,
      and cardiac magnetic resonance (CMR) left ventricular ejection fraction (LVEF)
      and infarct size at 4 to 6 months after the index event were available. RESULTS:
      In linear regression models, higher multimarker scores were associated with worse
      angiographic (P < .01 for both outcomes), electrocardiographic (P < .001 for the
      association with STR at last contrast, and P < .01 for STR at 240 minutes), and
      CMR outcomes (P < .01 for both). CONCLUSIONS: The multimarker risk score is
      associated with angiographic, electrocardiographic, and CMR mechanistic markers
      of outcomes. These data support the ability of the multimarker risk score to
      identify patients at high risk for suboptimal reperfusion and CMR outcomes and
      may aid in the early triage of patients who stand to benefit most of adjuvant
      treatments in STEMI.

PMID- 22607856
TI  - Physical function and independence 1 year after myocardial infarction:
      observations from the Translational Research Investigating Underlying disparities
      in recovery from acute Myocardial infarction: Patients' Health status registry.
AB  - BACKGROUND: Acute myocardial infarction (AMI) may contribute to health status
      declines including "independence loss" and "physical function decline." Despite
      the importance of these outcomes for prognosis and quality of life, their
      incidence and predictors have not been well described. METHODS: We studied 2,002
      patients with AMI enrolled across 24 sites in the TRIUMPH registry who completed
      assessments of independence and physical function at the time of AMI and 1 year
      later. Independence was evaluated by the EuroQol-5D (mobility, self-care, and
      usual activities), and physical function was assessed with the Short Form-12
      physical component score. Declines in >=1 level on EuroQol-5D and >5 points in
      PCS were considered clinically significant changes. Hierarchical, multivariable,
      modified Poisson regression models accounting for within-site variability were
      used to identify predictors of independence loss and physical function decline.
      RESULTS: One-year post AMI, 43.0% of patients experienced health status declines:
      12.8% independence loss alone, 15.2% physical function decline alone, and 15.0%
      both. After adjustment, variables that predicted independence loss included
      female sex, nonwhite race, unmarried status, uninsured status, end-stage renal
      disease, and depression. Variables that predicted physical function decline were
      uninsured status, lack of cardiac rehabilitation referral, and absence of pre-AMI
      angina. Age was not predictive of either outcome after adjustment. CONCLUSIONS:
      >40% of patients experience independence loss or physical function decline 1 year
      after AMI. These changes are distinct but can occur simultaneously. Although some
      risk factors are not modifiable, others suggest potential targets for strategies
      to preserve patients' health status.

PMID- 22607857
TI  - Variations in practice and outcomes in patients undergoing primary percutaneous
      coronary intervention in the United States and Canada: insights from the
      Assessment of Pexelizumab in Acute Myocardial Infarction (APEX AMI) trial.
AB  - BACKGROUND: Information on practice patterns and outcomes in patients with ST
      elevation myocardial infarction undergoing primary percutaneous coronary
      interventions (PCIs) in Canada vs United States is limited. METHODS: We evaluated
      differences in clinical and angiographic features, practice patterns, and
      outcomes between Canada and United States in 2,086 patients with ST-elevation
      myocardial infarction undergoing primary PCI in the APEX AMI trial. RESULTS: Of
      2,086 patients, 335 (19%) were enrolled in Canada. Compared with US patients,
      Canadians were older with lower body mass index and creatinine clearance and less
      likely to have history of hypertension, smoking, or prior revascularization.
      Baseline infarct artery patency was higher, and the use of intra-aortic balloon
      pump and drug-eluting stents was lower in Canadian patients. Median door-to-PCI
      time was significantly shorter among Canadian patients (0.9 hours [interquartile
      range 0.6-1.3] vs 1.2 hours [interquartile range 0.8-1.7]). Clinical outcomes at
      90 days were lower among Canadian patients, including shock (2.7% vs 4.2%), heart
      failure (3.6% vs 5.6%), bleeding (3.6% vs 9.6%), and atrial (3.6% vs 7.4%) and
      ventricular (3.0% vs 6.4%) arrhythmias. However, 90-day mortality (2.7% vs 4.8%,
      adjusted hazard ratio 0.62, 95% CI 0.47-1.28) and composite of death, shock, or
      heart failure (6.8% vs 11.5%, adjusted hazard ratio 0.77, 95% CI 0.47-1.27) were
      similar in the 2 cohorts. CONCLUSIONS: Compared with US patients, Canadian
      patients had shorter door-to-PCI time but similar 90-day outcomes. These data
      suggest an opportunity for US sites to examine and learn from the Canadian
      systems of processes of care and implement changes so as to improve the
      timeliness of primary PCI.

PMID- 22607859
TI  - Percutaneous left ventricular partitioning in patients with chronic heart failure
      and a prior anterior myocardial infarction: Results of the PercutAneous
      Ventricular RestorAtion in Chronic Heart failUre PaTiEnts Trial.
AB  - OBJECTIVES: The aim of this study was to assess the feasibility, safety, and
      preliminary efficacy of a novel percutaneous left ventricular partitioning device
      (VPD) in patients with chronic heart failure (HF) and a prior anterior myocardial
      infarction. BACKGROUND: Anterior myocardial infarction is frequently followed by
      left ventricular remodeling, HF, and increased long-term morbidity and mortality.
      METHODS: Thirty-nine patients were enrolled in a multinational, nonrandomized,
      longitudinal investigation. The primary end point was an assessment of safety,
      defined as the successful delivery and deployment of the VPD and absence of
      device-related major adverse cardiac events over 6 months. Secondary
      (exploratory) efficacy end points included changes in hemodynamics and functional
      status and were assessed serially throughout the study. RESULTS: Ventricular
      partitioning device placement was not attempted in 5 (13%) of 39 subjects. The
      device was safely and successfully implanted in 31 (91%) of the remaining 34
      patients or 79% of all enrolled patients. The 6-month rate of device-related
      major adverse cardiac event occurred in 5 (13%) of 39 enrolled subjects and 5
      (15%) of 34 treated subjects, with 1 additional event occurring between 6 and 12
      months. For patients discharged with the device to 12 months (n = 28), New York
      Heart Association class (2.5 +/- 0.6 to 1.3 +/- 0.6, P < .001) and quality-of
      life scores (38.6 +/- 6.1 to 28.4 +/- 4.4, P < .002) improved significantly;
      however, the 6-minute hall walk distance (358.5 +/- 20.4 m to 374.7 +/- 25.6 m, P
      nonsignificant) only trended toward improvement. CONCLUSIONS: The left VPD
      appears to be relatively safe and potentially effective in the treatment for
      patients with HF and a prior anterior myocardial infarction. However, these
      limited results suggest the need for further evaluation in a larger randomized
      controlled trial.

PMID- 22607858
TI  - International variation in use of oral anticoagulation among heart failure
      patients with atrial fibrillation.
AB  - BACKGROUND: We sought to characterize patient factors and regional variations
      associated with vitamin K antagonist (VKA) use in patients with heart failure
      (HF) and atrial fibrillation (AF) in areas outside the United States and Europe.
      METHODS: The ADHERE-International registry enrolled patients with decompensated
      HF from 10 Asia Pacific and Latin American countries from December 2005 to
      January 2009. Rates of VKA use in patients with HF and either new-onset AF or a
      history of AF were determined and compared according to CHADS(2) scores.
      Multivariable logistic regression and hierarchical modeling with random effects
      for hospitals were used to determine clinical and regional factors associated
      with VKA use at discharge. RESULTS: Among 9,706 admissions, there were 2,358
      (24.3%) with prior AF and 674 (6.9%) with new-onset AF. The median age was 71
      years (25th-75th percentiles 59-79) for prior AF and 69 (57-80) for new-onset AF
      patients. The overall rate of VKA use at discharge was 39.5%. Vitamin K
      antagonist use at discharge was 36.2% in patients with CHADS(2) scores >=2 versus
      50.2% in patients with CHADS(2) score equal to 1 (P < .0001). Vitamin K
      antagonist use was 36.4% in patients with hypertension, 28.1% in patients >75
      years old, 34.8% in diabetics, and 44.4% in those with prior stroke/transient
      ischemic attack. After adjusting for patient characteristics, the highest and
      lowest rates of anticoagulation were in Australia (65.2%) and Taiwan (25.1%).
      CONCLUSION: International use of guidelines-recommended anticoagulation in HF
      patients with AF varies significantly across countries and represents an
      important opportunity for improving quality of care.

PMID- 22607860
TI  - Combined use of high-sensitivity cardiac troponin T and N-terminal pro-B type
      natriuretic peptide improves measurements of performance over established
      mortality risk factors in chronic heart failure.
AB  - BACKGROUND: Heart failure still maintains a high mortality. Biomarkers reflecting
      different pathophysiological pathways are under evaluation to better stratify the
      mortality risk. The objective was to assess high-sensitivity cardiac troponin T
      (hs-cTnT) in combination with N-terminal pro-B type natriuretic peptide (NT
      proBNP) for risk stratification in a real-life cohort of ambulatory heart failure
      patients. METHODS: We analyzed 876 consecutive patients (median age 70.3 years,
      median left ventricular ejection fraction 34%) treated at a heart failure unit. A
      combination of biomarkers reflecting myocyte injury (hs-cTnT) and myocardial
      stretch (NT-proBNP) was used in addition to an assessment based on established
      mortality risk factors (age, sex, left ventricular ejection fraction, New York
      Heart Association functional class, diabetes, estimated glomerular filtration
      rate, ischemic etiology, sodium, hemoglobin, beta-blocker treatment, and
      angiotensin converting enzyme inhibitor or angiotensin II receptor blocker
      treatment). RESULTS: During a median follow-up of 41.4 months, 311 patients died.
      In the multivariable Cox proportional hazards model, hs-cTnT and NT-proBNP were
      independent prognosticators (P = .003 each). The combined elevation of both
      biomarkers above cut-off values significantly increased the risk of death (HR
      7.42 [95% CI, 5.23-10.54], P < .001). When hs-cTnT and NT-proBNP were
      individually included in a model with established mortality risk factors,
      measurements of performance significantly improved. Results obtained for hs-cTnT
      compared with NT-proBNP were superior according to comprehensive discrimination,
      calibration, and reclassification analysis (net reclassification indices of 7.7%
      and 1.5%, respectively). CONCLUSIONS: hs-cTnT provides significant prognostic
      information in a real-life cohort of patients with chronic heart failure.
      Simultaneous addition of hs-cTnT and NT-proBNP into a model that includes
      established risk factors improves mortality risk stratification.

PMID- 22607861
TI  - The changing definition of contrast-induced nephropathy and its clinical
      implications: insights from the Blue Cross Blue Shield of Michigan Cardiovascular
      Consortium (BMC2).
AB  - BACKGROUND: The traditional definition of contrast-induced nephropathy (CIN) has
      been an absolute rise of serum creatinine (Cr) of >=0.5 mg/dL, although most
      recent clinical trials have included a >=25% increase from baseline Cr. The
      clinical implication of this definition change remains unknown. METHODS AND
      RESULTS: We compared the association of the two definitions with risk of death or
      need for dialysis among 58,957 patients undergoing percutaneous coronary
      intervention in 2007 to 2008 in a large collaborative registry. Patients with a
      preexisting history of renal failure requiring dialysis were excluded. Contrast
      induced nephropathy as defined by a rise in Cr >=0.5 mg/dL (CIN(Traditional))
      developed in 1,601, whereas CIN defined either as Cr >=0.5 mg/dL or >=25%
      increase in baseline Cr (CIN(New)) developed in 4,308 patients. Patients meeting
      the definition of CIN(New) but not CIN(Traditional) were classified as
      CIN(Incremental) (n = 2,707). Compared with CIN(New), CIN(Traditional) was more
      commonly seen in patients with abnormal renal function, which was more likely to
      develop in patients with normal renal function at baseline. Compared with
      CIN(Incremental), patients meeting the definition of CIN(Traditional) were more
      likely to die (16.7% vs 1.7%) and require in-hospital dialysis (9.8% vs 0%).
      CONCLUSIONS: Our data suggest that the traditional definition of CIN (a rise in
      Cr of >=0.5 mg/dL) in patients undergoing PCI is superior to >=25% increase in Cr
      at identifying patients at greater risk for adverse renal and cardiac events.

PMID- 22607862
TI  - Understanding childhood obesity in America: linkages between household income,
      community resources, and children's behaviors.
AB  - BACKGROUND: Understanding childhood obesity's root causes is critical to the
      creation of strategies to improve our children's health. We sought to define the
      association between childhood obesity and household income and how household
      income and childhood behaviors promote childhood obesity. METHODS: We assessed
      body mass index in 109,634 Massachusetts children, identifying the percentage of
      children who were overweight/obese versus the percentage of children in each
      community residing in low-income homes. We compared activity patterns and diet in
      999 sixth graders residing in 4 Michigan communities with varying annual
      household income. RESULTS: In Massachusetts, percentage of overweight/obese by
      community varied from 9.6% to 42.8%. As household income dropped, percentage of
      overweight/obese children rose. In Michigan sixth graders, as household income
      goes down, frequency of fried food consumption per day doubles from 0.23 to 0.54
      (P < .002), and daily TV/video time triples from 0.55 to 2.00 hours (P < .001),
      whereas vegetable consumption and moderate/vigorous exercise go down.
      CONCLUSIONS: The prevalence of overweight/obese children rises in communities
      with lower household income. Children residing in lower income communities
      exhibit poorer dietary and physical activity behaviors, which affect obesity.

PMID- 22607863
TI  - Baseline metabolomic profiles predict cardiovascular events in patients at risk
      for coronary artery disease.
AB  - BACKGROUND: Cardiovascular risk models remain incomplete. Small-molecule
      metabolites may reflect underlying disease and, as such, serve as novel
      biomarkers of cardiovascular risk. METHODS: We studied 2,023 consecutive patients
      undergoing cardiac catheterization. Mass spectrometry profiling of 69 metabolites
      and lipid assessments were performed in fasting plasma. Principal component
      analysis reduced metabolites to a smaller number of uncorrelated factors.
      Independent relationships between factors and time-to-clinical events were
      assessed using Cox modeling. Clinical and metabolomic models were compared using
      log-likelihood and reclassification analyses. RESULTS: At median follow-up of 3.1
      years, there were 232 deaths and 294 death/myocardial infarction (MI) events.
      Five of 13 metabolite factors were independently associated with mortality:
      factor 1 (medium-chain acylcarnitines: hazard ratio [HR] 1.12 [95% CI, 1.04
      1.21], P = .005), factor 2 (short-chain dicarboxylacylcarnitines: HR 1.17 [1.05
      1.31], P = .005), factor 3 (long-chain dicarboxylacylcarnitines: HR 1.14 [1.05
      1.25], P = .002); factor 6 (branched-chain amino acids: HR 0.86 [0.75-0.99], P =
      .03), and factor 12 (fatty acids: HR 1.19 [1.06-1.35], P = .004). Three factors
      independently predicted death/MI: factor 2 (HR 1.11 [1.01-1.23], P = .04), factor
      3 (HR 1.13 [1.04-1.22], P = .005), and factor 12 (HR 1.18 [1.05-1.32], P = .004).
      For mortality, 27% of intermediate-risk patients were correctly reclassified (net
      reclassification improvement 8.8%, integrated discrimination index 0.017); for
      death/MI model, 11% were correctly reclassified (net reclassification improvement
      3.9%, integrated discrimination index 0.012). CONCLUSIONS: Metabolic profiles
      predict cardiovascular events independently of standard predictors.

PMID- 22607864
TI  - Retrospective cohort analysis of 926 tricuspid valve surgeries: clinical and
      hemodynamic outcomes with propensity score analysis.
AB  - BACKGROUND: The objectives were to describe morbidity and mortality after
      tricuspid valve (TV) surgery, to compare outcomes after repair versus
      replacement, and to assess risk factors for mortality and tricuspid regurgitation
      (TR) recurrence. METHODS: A retrospective cohort study including 926 consecutive
      cases of TV surgery (792 repairs and 134 replacements) performed at the Montreal
      Heart Institute was conducted. Median follow-up was 4.3 years (4,657 patient
      years). Median age was 62 years (interquartile range 53-69 years), and 72% of
      patients were women. RESULTS: Operative mortality was 14% (128 patients: 1977
      1998 20%, 1999-2008 7%, P < .001). Independent risk factors for operative
      mortality in the 1999 to 2008 period were hypertension (odds ratio [OR] 6.03, P =
      .02), daily furosemide dose (by 10 mg) (OR 1.06, P = .05), weight (by 10 kg) (OR
      0.36, P < .01), and cardiopulmonary bypass time (by 10 minutes) (OR 1.29, P <
      .001). Ten-year survival was 49% +/- 2% and 38 +/- 5% in the repair and
      replacement groups, respectively (P = .012). At discharge, severity of TR was
      >=3/4 in 13% and 2% of patients in the repair and replacement groups,
      respectively (P = .01). Propensity score analysis showed that tricuspid repair
      was associated with higher rates of TR >=3/4 at follow-up compared with
      replacement (hazard ratio 2.15, P = .02). Forty-eight reoperations (7% of
      patients at risk) were performed during follow-up (repair group, 6%; replacement
      group, 15%; P = .01). At last follow-up, New York Heart Association functional
      class was improved compared with baseline in both groups (P < .001). CONCLUSION:
      Tricuspid valve surgery is associated with substantial early and late mortalities
      but with significant functional improvement. Replacement is more effective in
      early and late corrections of regurgitation, but it does not translate into
      better survival outcomes.

PMID- 22607865
TI  - Systemic right ventricular longitudinal strain is reduced in adults with
      transposition of the great arteries, relates to subpulmonary ventricular
      function, and predicts adverse clinical outcome.
AB  - BACKGROUND: Transposition of the great arteries (TGA) after atrial switch
      operation and congenitally corrected TGA (ccTGA) are commonly associated with
      impaired systemic right ventricular (RV) function and impaired prognosis. We
      aimed to investigate the value of indices of myocardial deformation on speckle
      tracking echocardiography for quantifying ventricular function and their
      potential role in assessing ventricular-ventricular interaction and outcome in
      patients with a systemic RV. METHODS AND RESULTS: A total of 129 patients (87
      with TGA and atrial switch and 42 with ccTGA, 71 men, age 35 +/- 12 years) were
      investigated, and biventricular myocardial deformation was compared with findings
      in healthy subjects (n = 38, age 36 +/- 10 years). Systemic ventricular
      longitudinal 2-dimensional (2D) peak systolic strain (RV 2D-LS) was significantly
      reduced compared with controls (-12.9 +/- 3.6 and -15.4 +/- 5.1 vs -21.0 +/- 5.5
      in TGAs, ccTGAs, and controls, P < .0001). Systemic and pulmonary 2D-LS were
      correlated in patients with TGA (r = 0.46, P < .0001) and ccTGA (r = 0.64, P <
      .0001), suggesting interventricular interaction, and this was confirmed when
      ejection fraction on magnetic resonance imaging was assessed (r = 0.53, P <
      .0001). More importantly, systemic 2D-LS (hazard ratio 1.31, P = .01) was related
      to adverse clinical outcome (symptomatic progression to New York Heart
      Association class >=3, clinically relevant cardiac arrhythmia, or death) in
      patients with TGA and atrial switch independently of ejection fraction on cardiac
      magnetic resonance imaging, history of clinically relevant arrhythmia, or
      functional class. CONCLUSIONS: Global longitudinal systolic strain is
      significantly reduced in patients with a systemic RV, is related to subpulmonary
      ventricular function, and predicts adverse clinical outcome in adults with atrial
      switch TGA.

PMID- 22607866
TI  - The SPIRIT V diabetic study: a randomized clinical evaluation of the XIENCE V
      everolimus-eluting stent vs the TAXUS Liberte paclitaxel-eluting stent in
      diabetic patients with de novo coronary artery lesions.
AB  - BACKGROUND: Diabetic patients respond less favorably to revascularization and
      have poorer long-term outcomes. Our main aim was to evaluate the angiographic
      efficacy of XIENCE V (everolimus-eluting stent, or EES) in diabetic patients
      compared with TAXUS Liberte (paclitaxel-eluting stent, or PES). METHODS: The
      SPIRIT V Diabetic Study was a prospective, single-blind, randomized study that
      enrolled 324 diabetic (insulin and non-insulin dependent) patients at 28 sites in
      Europe and Asia Pacific. Randomization was 2:1 between EES (n = 218) and PES (n =
      106). The primary end point was sequential noninferiority and superiority of EES
      for in-stent late loss at 9 months. Secondary clinical end points included stent
      thrombosis, death, myocardial infarction, and revascularization rates up to 1
      year. RESULTS: Everolimus-eluting stent was superior to PES for in-stent late
      loss at 9 months (0.19 mm vs 0.39 mm, respectively; P(superiority) = .0001). The
      composite rate of death, myocardial infarction, and target vessel
      revascularization was the same in the 2 groups at 1 year (16.3% vs 16.4%). No
      stent thromboses (Academic Research Consortium definite and probable) were seen
      through 1 year with EES compared with 2 of 104 (2%) with PES (P = .11).
      CONCLUSION: In this prospective, randomized trial in a high-risk group of
      diabetic patients, implantation of EES compared with PES resulted in
      significantly better inhibition of intimal hyperplasia with a comparable safety
      outcome.

PMID- 22607867
TI  - Long-term clinical and angiographic outcomes of diabetic patients after
      revascularization with early generation drug-eluting stents.
AB  - BACKGROUND: Early generation drug-eluting stents (DESs) reduce restenosis and
      repeat revascularization procedures. However, the long-term safety and efficacy
      of early generation DES according to diabetic status are poorly established.
      METHODS: A total of 1,012 patients were randomly assigned to treatment with
      sirolimus-eluting (n = 503) or paclitaxel-eluting stents (n = 509). Serial
      angiographic follow-up at baseline, 8 months, and 5 years was available in 293
      patients with 382 lesions. The primary end point was a composite of major adverse
      cardiac events (cardiac death, myocardial infarction, and ischemia-driven target
      lesion revascularization). Clinical and angiographic outcomes through 5-year
      follow-up were compared between diabetic and nondiabetic patients. RESULTS: Major
      adverse cardiac events were more common among diabetic than nondiabetic patients
      at 5 years (25.9% vs 19.2%, hazard ratio [HR] 1.45, 95% CI 1.06-1.99, P = .02).
      The difference in disfavor of diabetic patients was largely determined by a
      higher rate of cardiac mortality (11.4% vs 4.3%, HR 2.86, 95% CI 1.69-4.84, P <
      .0001), whereas the risk of myocardial infarction (6.5% vs 6.8%, HR 1.00, 95% CI
      0.55-1.84, P = .99) and ischemia-driven target lesion revascularization (14.4% vs
      14.1%, HR 1.09, 95% CI 0.73-1.64, P = .67) was comparable. The risk of stent
      thrombosis was similar among diabetic and nondiabetic patients (definite or
      probable: 6.0% vs 4.6%, HR 1.36, 95% CI 0.71-2.67, P = .35). Among 293 patients
      undergoing serial angiography, very-late lumen loss amounted to 0.42 +/- 0.63 mm
      in diabetic patients and 0.44 +/- 0.68 mm in nondiabetic patients (P = .79).
      CONCLUSIONS: Diabetic patients remain at increased risk for mortality after
      revascularization with early generation DES during long-term follow-up.
      Conversely, diabetes is no longer associated with an increased risk of clinical
      and angiographic restenosis after revascularization with early generation DES.

PMID- 22607868
TI  - Progression of atrial fibrillation in the REgistry on Cardiac rhythm disORDers
      assessing the control of Atrial Fibrillation cohort: clinical correlates and the
      effect of rhythm-control therapy.
AB  - INTRODUCTION: Paroxysmal atrial fibrillation (AF) may progress to persistent AF.
      We studied the clinical correlates and the effect of rhythm-control strategy on
      AF progression. METHODS: RecordAF was a worldwide prospective survey of AF
      management. Consecutive eligible patients with recent-onset AF were included and
      allocated to rate or rhythm control according to patient/physician choice. A
      total of 2,137 patients were followed up for 12 months. Atrial fibrillation
      progression was defined as a change from paroxysmal to persistent/permanent AF.
      RESULTS: Progression of AF occurred in 318 patients (15%) after 1 year. Patients
      with AF progression were older; had a higher diastolic blood pressure; and more
      often had a history of coronary artery disease, stroke or transient ischemic
      attack, hypertension, or heart failure. Patients treated with rhythm control were
      less likely to show progression than those treated only with rate control
      (164/1542 [11%] vs 154/595 [26%], P < .001). Multivariable analysis showed that
      history of heart failure (odds ratio [OR] 2.2, 95% CI 1.7-2.9, P < .0001),
      history of hypertension (OR 1.5, 95% CI 1.1-2.0, P = .01), and rate control
      rather than rhythm control (OR 3.2, 95% CI 2.5-4.1, P < .0001) were independent
      predictors of AF progression. The propensity score-adjusted OR of AF progression
      in patients with rate rather than rhythm control was 3.3 (95% CI 2.4-4.6, P <
      .0001). CONCLUSIONS: Although heart failure and hypertension are associated with
      AF progression, rhythm control is associated with lower risk of AF progression.

PMID- 22607869
TI  - Trends in endocarditis hospitalizations at US children's hospitals: impact of the
      2007 American Heart Association Antibiotic Prophylaxis Guidelines.
AB  - BACKGROUND: In 2007, the American Heart Association recommended cessation of
      antibiotic prophylaxis for infective endocarditis (IE) before dental procedures
      for all but those at highest risk for adverse outcomes from IE. The impact of
      these guidelines is unclear. We evaluated IE hospitalizations at US children's
      hospitals during this period. METHODS: Children <18 years old hospitalized from
      2003 to 2010 with IE at 37 centers in the Pediatric Health Information Systems
      Database were included. Using Poisson regression, we evaluated the number IE
      hospitalizations over time (raw and indexed to total hospital admissions).
      RESULTS: A total of 1157 IE cases were identified; 68% had congenital heart
      disease (CHD). The raw number of IE cases did not change significantly over time
      (+1.6% difference post vs pre guidelines, 95% CI -6.4% to +10.3%, P = .7). When
      the number of IE cases was indexed per 1,000 hospital admissions, there was a
      significant decline during the time period before the guidelines (annual change: 
      5.9%, 95% CI -9.9 to -1.8, P = .005) and a similar decline in the post guidelines
      period such that the difference between the 2 periods was not significant (P =
      .15). In subgroup analysis, no significant change over time in IE cases (raw or
      indexed) was found in the CHD subset, those 5 to 18 years old (subgroup most
      likely receiving dental care), or in cases coded as oral streptococci.
      CONCLUSIONS: We found no evidence that release of new antibiotic prophylaxis
      guidelines was associated with a significant change in IE admissions across 37 US
      children's hospitals.

PMID- 22607870
TI  - Assessing the role of eptifibatide in patients with diffuse coronary disease
      undergoing drug-eluting stenting: the INtegrilin plus STenting to Avoid
      myocardial Necrosis Trial.
AB  - BACKGROUND: The optimal antiplatelet regimen in elective patients undergoing
      complex percutaneous coronary interventions (PCIs) is uncertain. We aimed to
      assess the impact of glycoprotein IIb/IIIa (GpIIb/IIIa) inhibition with
      eptifibatide in clinically stable subjects with diffuse coronary lesions.
      METHODS: Patients with stable coronary artery disease undergoing PCI by means of
      implantation of >33 mm of drug-eluting stent were single-blindedly randomized to
      heparin plus eptifibatide versus heparin alone. The primary end point was the
      rate of abnormal post-PCI creatine kinase-MB mass values. Secondary end points
      were major adverse cardiovascular events (MACEs) (ie, cardiac death, myocardial
      infarction, or urgent revascularization) and MACE plus bailout GpIIb/IIIa
      inhibitor use. RESULTS: The study was stopped for slow enrollment and funding
      issues after including a total of 91 patients: 44 were randomized to heparin plus
      eptifibatide, and 47, to heparin alone. Analysis for the primary end point showed
      a trend toward lower rates of abnormal post-PCI creatine kinase-MB mass values in
      the heparin-plus-eptifibatide group (18 [41%]) versus the heparin-alone group (26
      [55%], relative risk 0.74 [95% CI 0.48-1.15], P = .169). Similar nonstatistically
      significant trends were found for rates of MACE, their components, or MACE plus
      bailout GpIIb/IIIa inhibitors (all P > .05). Notably, heparin plus eptifibatide
      proved remarkably safe because major bleedings or minor bleeding was uncommon and
      nonsignificantly different in both groups (all P > .05). CONCLUSIONS: Given its
      lack of statistical power, the INSTANT study cannot definitively provide evidence
      against or in favor of routine eptifibatide administration in stable patients
      undergoing implantation of multiple drug-eluting stent for diffuse coronary
      disease. However, the favorable trend evident for the primary end point warrants
      further larger randomized studies.

PMID- 22607871
TI  - Regarding the "Platelet reactivity in patients with chronic kidney disease
      receiving adjunctive cilostazol compared with a high-maintenance dose of
      clopidogrel: Results of the Effect of Platelet Inhibition According to
      Clopidogrel Dose in Patients with Chronic Kidney Disease (PIANO-2 CKD) randomized
      study".

PMID- 22607873
TI  - Intensive glycemic control and the risk of heart failure in patients with type 2
      diabetes.

PMID- 22607875
TI  - Preanalytic considerations for using plasma myeloperoxidase as a biomarker in
      acute coronary syndrome.

PMID- 22607877
TI  - Design, synthesis and biological evaluation of novel amino acid ureido
      derivatives as aminopeptidase N/CD13 inhibitors.
AB  - A series of amino acid ureido derivatives as aminopeptidase N (APN/CD13)
      inhibitors were synthesized and evaluated for their APN inhibitory activities and
      anti-cancer effects. The results showed that most of these amino acid ureido
      derivatives exhibited good inhibition against APN, several of which were better
      than Bestatin. The most active compound 12j (IC(50) = 1.1 MUM, compared with
      Bestatin IC(50) = 8.1 MUM) not only possessed much better APN inhibitory activity
      and anti-proliferation effect on cancer cells, but also exhibited significant
      block effect of human cancer cell invasion compared with the positive control,
      Bestatin. These amino acid ureido derivatives could be possibly developed as new
      APN inhibitors for cancer chemotherapy in the future.

PMID- 22607878
TI  - Identification of novel drug-resistant EGFR mutant inhibitors by in silico
      screening using comprehensive assessments of protein structures.
AB  - EGFR is a target protein for the treatment of non small cell lung cancer (NSCLC).
      The mutations associated with the activation of EGFR kinase activity, such as
      L858R and G719S, destabilize the inactive conformation of EGFR and are closely
      linked with the development of NSCLC. The additional T790M mutation reportedly
      causes drug resistance against the commercially available EGFR inhibitors,
      gefitinib and erlotinib. In this study, we searched for novel G719S/T790M EGFR
      inhibitors by a new in silico screening strategy, using two datasets. The results
      of in silico screening using protein-ligand docking are affected by the selection
      of 3D structure of the target protein. As the first strategy, we chose the 3D
      structures for in silico screening by test dockings using the G719S/T790M crystal
      structure, its molecular dynamics snapshots, and known inhibitors of the drug
      resistant EGFR. In the second strategy, we selected the 3D structures by test
      dockings using all of the EGFR structures, regardless of the mutations, and all
      of the known EGFR inhibitors. Using each of the 3D structures selected by the
      strategies, 1000 compounds were chosen from the 71,588 compounds. Kinase assays
      identified 15 G719S/T790M EGFR inhibitors, including two compounds with novel
      scaffolds. Analyses of their structure-activity relationships revealed that
      interactions with the mutated Met790 residue specifically increase the inhibitory
      activity against G719S/T790M EGFR.

PMID- 22607879
TI  - Synthesis, enantioresolution, and activity profile of chiral 6-methyl-2,4
      disubstituted pyridazin-3(2H)-ones as potent N-formyl peptide receptor agonists.
AB  - A series of chiral pyridazin-3(2H)-ones was synthesized, separated as pure
      enantiomers, and evaluated for N-formyl peptide receptor (FPR) agonist activity.
      Characterization of the purified enantiomers using combined chiral HPLC and
      chiroptical studies (circular dichroism, allowed unambiguous assignment of the
      absolute configuration for each pair of enantiomers). Evaluation of the ability
      of racemic mixtures and purified enantiomers to stimulate intracellular Ca(2+)
      flux in FPR-transfected HL-60 cells and human neutrophils and to induce beta
      arrestin recruitment in FPR-transfected CHO-K1 cells showed that many enantiomers
      were potent agonists, inducing responses in the sub-micromolar to nanomolar
      range. Furthermore, FPRs exhibited enantiomer selectivity, generally preferring
      the R-(-)-forms over the S-(+)-enantiomers. Finally, we found that elongation of
      the carbon chain in the chiral center of the active compounds generally increased
      biological activity. Thus, these studies provide important new information
      regarding molecular features involved in FPR ligand preference and report the
      identification of a novel series of FPR agonists.

PMID- 22607880
TI  - Identification of novel benzimidazole derivatives as inhibitors of leukotriene
      biosynthesis by virtual screening targeting 5-lipoxygenase-activating protein
      (FLAP).
AB  - Pharmacological suppression of leukotriene biosynthesis by 5-lipoxygenase (5-LO)
      activating protein (FLAP) inhibitors is a promising strategy to intervene with
      inflammatory, allergic and cardiovascular diseases. Virtual screening targeting
      FLAP based on a combined ligand- and structure-based pharmacophore model led to
      the identification of 1-(2-chlorobenzyl)-2-(1-(4-isobutylphenyl)ethyl)-1H
      benzimidazole (7) as developable candidate. Compound 7 potently suppressed
      leukotriene formation in intact neutrophils (IC(50)=0.31 MUM) but essentially
      failed to directly inhibit 5-LO suggesting that interaction with FLAP causes
      inhibition of leukotriene synthesis. For structural optimization, a series of 46
      benzimidazole-based derivatives of 7 were synthesized leading to more potent
      analogues (70-72, 82) with IC(50)=0.12-0.19 MUM in intact neutrophils. Together,
      our results disclose the benzimidazole scaffold bearing an ibuprofen fingerprint
      as a new chemotype for further development of anti-leukotriene agents.

PMID- 22607881
TI  - Change or be changed: reflections of the workshop 'Future in Medicinal
      Chemistry'.

PMID- 22607882
TI  - Synthesis of [(11)C]dehydropravastatin, a PET probe potentially useful for
      studying OATP1B1 and MRP2 transporters in the liver.
AB  - Drug transporters mediate the uptake and elimination of drugs in various organs;
      therefore, having knowledge of how a transporter functions in the body would play
      a key role in ensuring drug efficacy in in vivo systems. In this context, we
      designed and synthesized [(11)C]dehydropravastatin, a novel PET probe that would
      be potentially useful for evaluation of the functions of the OATP1B1 and MRP2
      transporters, based on the use of palladium(0)-mediated rapid C
      [(11)C]methylation (viz., the rapid cross-coupling between [(11)C]methyl iodide
      and a boron intermediate).

PMID- 22607883
TI  - Synthesis and antiviral activity of certain second generation
      methylenecyclopropane nucleosides.
AB  - A second-generation series of substituted methylenecyclopropane nucleosides
      (MCPNs) has been synthesized and evaluated for antiviral activity against a panel
      of human herpesviruses, and for cytotoxicity. Although alkylated 2,6
      diaminopurine analogs showed little antiviral activity, the compounds containing
      ether and thioether substituents at the 6-position of the purine did demonstrate
      potent and selective antiviral activity against several different human
      herpesviruses. In the 6-alkoxy series, antiviral activity depended on the length
      of the ether carbon chain, with the optimum chain length being about four carbon
      units long. For the corresponding thioethers, compounds containing secondary
      thioethers were more potent than those with primary thioethers.

PMID- 22607884
TI  - Structure, function and applications of carbonic anhydrase isozymes.
AB  - The carbonic anhydrases enzymes (CAs, EC 4.2.1.1) are zinc containing
      metalloproteins, which efficiently catalyse the reversible conversion of carbon
      dioxide to bicarbonate and release proton. These enzymes are essentially
      important for biological system and play several important physiological and
      patho-physiological functions. There are 16 different alpha-carbonic anhydrase
      isoforms studied, differing widely in their cellular localization and biophysical
      properties. The catalytic domains of all CAs possess a conserved tertiary
      structure fold, with predominately beta-strands. We performed an extensive
      analysis of all 16 mammalian CAs for its structure and function in order to
      establish a structure-function relationship. CAs have been a potential
      therapeutic target for many diseases. Sulfonamides are considered as a strong and
      specific inhibitor of CA, and are being used as diuretics, anti-glaucoma, anti
      epileptic, anti-ulcer agents. Currently CA inhibitors are widely used as a drug
      for the treatment of neurological disorders, anti-glaucoma drugs, anti-cancer, or
      anti-obesity agents. Here we tried to emphasize how CAs can be used for drug
      discovery, design and screening. Furthermore, we discussed the role of CA in
      carbon capture, carbon sensor and metabolon. We hope this review provide many
      useful information on structure, function, mechanism, and applications of CAs in
      various discipline.

PMID- 22607886
TI  - Assessment of right ventricular systolic function in patients with pulmonary
      hypertension.

PMID- 22607885
TI  - Pretransplant fecal carriage of extended-spectrum beta-lactamase-producing
      Enterobacteriaceae and infection after liver transplant, France.
AB  - Extended-spectrum beta-lactamase-producing Enterobacteriaceae isolates (ESBLE)
      are emerging pathogens that confer resistance to antimicrobial drugs. We
      conducted a 10-year study in France (January 2001-April 2010) to investigate the
      incidence of and risk factors for ESBLE infections after liver transplant. Of 710
      transplant patients screened preoperatively for ESBLE fecal carriage, 5.5% had
      ESBLE infection develop within 4 months after surgery; patients with
      pretransplant ESBLE fecal carriage were more likely to have infection develop
      than were noncarriers. Typing showed extensive genetic diversity, with a large
      predominance of CTX-M enzymes. Independent predictors of ESBLE infection were
      pretransplant fecal carriage, Model for End Stage Liver Disease score >25, and
      return to surgery. Our results indicate that the influx of preoperatively
      acquired ESBLE isolates into the hospital outweighs cross-transmission in the
      epidemiology of ESBLE infections after liver transplant. Transplant candidates
      should be systematically screened for carriage, and posttransplant infection in
      carriers should be treated with carbapenems.

PMID- 22607887
TI  - Inflammatory and thrombotic markers in patients with ST-elevation myocardial
      infarction treated with thrombolysis and early PCI: a NORDISTEMI substudy.
AB  - INTRODUCTION: Both pharmacological and invasive treatment might influence the
      inflammatory and pro-thrombotic responses observed in acute ST-elevation
      myocardial infarction (STEMI). We aimed to study whether circulating levels of
      inflammatory and pro-thrombotic markers differ in STEMI patients treated with
      early angioplasty compared to standard therapy following thrombolysis.
      Furthermore, we wanted to study if levels of markers were related to infarct
      size. MATERIALS AND METHODS: This was a substudy of the NORwegian study on
      DIstrict treatment of ST-Elevation Myocardial Infarction (NORDISTEMI), in which
      STEMI patients treated with thrombolysis were randomized to early invasive or
      standard therapy. Fasting blood samples were collected in the morning 3 days and
      3 months after onset of STEMI. Commercially available ELISA methods were used for
      determination of inflammatory and pro-thrombotic markers. Infarct size was
      assessed by SPECT after 3 months. RESULTS: 246 patients were included in this
      substudy. At 3 days, levels of prothrombin fragment 1+2 and D-dimer were higher
      in the early invasive compared to the standard treatment group, whereas levels of
      soluble CD40 ligand were lower (p<0.01 for all). No other differences between
      groups were found in any of the measured markers. Significant, although weak
      correlations were found between Day 3 levels of C-reactive protein, interleukin
      6, prothrombin fragment 1+2 and D-dimer, and infarct size assessed by SPECT after
      3 months. CONCLUSIONS: An early invasive strategy following thrombolysis for
      STEMI was associated with higher subacute levels of D-dimer and prothrombin
      fragment 1+2, and lower levels of soluble CD40 ligand than standard treatment.
      Further studies are needed to establish the relation between these changes and
      clinical outcome. The NORDISTEMI was registered at www.clinicaltrials.gov,
      NCT00161005.

PMID- 22607889
TI  - Body mass index and short-term weight change in relation to treatment outcomes in
      women undergoing assisted reproduction.
AB  - OBJECTIVE: To assess the relation between body mass index (BMI) and short-term
      weight change with assisted reproductive technology (ART) outcomes. DESIGN:
      Prospective cohort study. SETTING: Fertility center. PATIENT(S): A total of 170
      women undergoing 233 ART cycles. INTERVENTION(S): Baseline BMI and short-term
      weight change were related to ART outcomes. Regression models accounting for
      repeated observations were used to adjust data for potential confounders. MAIN
      OUTCOME MEASURE(S): Peak E2 levels, oocyte yield, MII yield, fertilization rate,
      embryo quality, postive [beta]-hCH, clinical pregnancy and live birth rates.
      RESULT(S): Overweight and obesity were associated with lower live birth rates.
      The adjusted live birth rate (95% confidence interval) was 42% (28%-58%) among
      women with a BMI between 20 and 22.4 kg/m(2) and 23% (14%-36%) among overweight
      or obese women. Short-term weight loss was associated with a higher proportion of
      metaphase II (MII) oocytes retrieved. The adjusted proportion of MII eggs was 91%
      (87%-94%) for women who lost 3 kg or more and 86% (81%-89%) for women whose
      weight remained stable. This association was stronger among women who were
      overweight or obese at baseline. Short-term weight loss was unrelated to positive
      beta-hCG, clinical pregnancy, or live birth rates. CONCLUSION(S): Overweight and
      obesity were related to lower live birth rates in women undergoing ART. Short
      term weight loss was related to higher MII yield, particularly among overweight
      and obese women, but unrelated to clinical outcomes.

PMID- 22607890
TI  - Animal models of polycystic ovary syndrome: a focused review of rodent models in
      relationship to clinical phenotypes and cardiometabolic risk.
AB  - OBJECTIVE: To review rodent animal models of polycystic ovary syndrome (PCOS),
      with a focus on those associated with the metabolic syndrome and cardiovascular
      disease risk factors. DESIGN: Review. ANIMAL(S): Rodent models of PCOS.
      INTERVENTION(S): Description and comparison of animal models. MAIN OUTCOME
      MEASURE(S): Comparison of animal models to clinical phenotypes of PCOS.
      RESULT(S): Animals used to study PCOS include rodents, mice, rhesus monkeys, and
      ewes. Major methods to induce PCOS in these models include subcutaneous injection
      or implantation of androgens, estrogens, antiprogesterone, letrozole, prenatal
      exposure to excess androgens, and exposure to constant light. In addition,
      transgenic mice models and spontaneous PCOS-like rodent models have also been
      developed. CONCLUSION(S): Rodents are the most economical and widely used animals
      to study PCOS and ovarian dysfunction. The model chosen to study the development
      of PCOS and other metabolic parameters remains dependent on the specific
      etiologic hypotheses being investigated. Rodent models have been shown to
      demonstrate changes in insulin metabolism, with or without induction of
      hyperandrogenemia, and limited studies have investigated cardiometabolic risk
      factors for type 2 diabetes and cardiovascular disease. Given the clinical
      heterogeneity of PCOS, the utilization of different animal models may be the best
      approach to further our understanding of the pathophysiologic mechanisms
      associated with the early etiology of PCOS and cardiometabolic risk.

PMID- 22607891
TI  - Reduced pretreatment ovarian reserve in premenopausal female patients with
      Hodgkin lymphoma or non-Hodgkin-lymphoma--evaluation by using antimullerian
      hormone and retrieved oocytes.
AB  - OBJECTIVE: To study whether the ovarian reserve in female lymphoma patients is
      already reduced before the start of chemotherapy. DESIGN: Age-matched control
      study. SETTING: Women's university hospital. PATIENT(S): Female patients aged <40
      years with the initial diagnosis of lymphoma (study group) were compared with age
      matched healthy volunteers (control group). Eighty-four female patients with
      breast cancer and 64 patients with lymphoma who underwent ovarian hormonal
      stimulation as a fertility-preserving method before the start of chemotherapy.
      INTERVENTION(S): Measurement of antimullerian-hormone (AMH) levels. Ovarian
      hormonal stimulation to retrieve oocytes. MAIN OUTCOME MEASURE(S): AMH levels of
      the lymphoma patients and the healthy volunteers were compared. Numbers of
      retrieved oocytes after hormonal stimulation in patients with breast cancer and
      those with lymphoma were compared. RESULT(S): Female lymphoma patients have
      significantly lower AMH levels than healthy age-matched controls: mean value of
      AMH was 2.06 ng/mL in the study group versus 3.20 ng/mL in the control group.
      Analysis of the stimulation results showed that in significantly younger patients
      with lymphoma, significantly fewer oocytes could be retrieved in comparison to
      those with breast cancer. CONCLUSION(S): Ovarian reserve is reduced in female
      patients affected by lymphoma even before the start of chemotherapy. Proper
      counseling and implementation of fertility-preserving methods is highly
      recommended.

PMID- 22607892
TI  - Adipose expression of adipocytokines in women with polycystic ovary syndrome.
AB  - OBJECTIVE: To investigate the role of adipocytokines in the pathophysiology of
      polycystic ovary syndrome (PCOS) by analyzing the messenger RNA (mRNA) expression
      and plasma levels of adipocytokines. DESIGN: Cross sectional study. SETTING:
      Hospital. PATIENT(S): Thirty-six women with PCOS, 17 lean (LP) and 19 obese (OP),
      and 24 age- and weight-matched controls, 8 lean (LC) and 16 obese (OC).
      INTERVENTION(S): Subcutaneous adipose tissue and fasting plasma samples collected
      from 60 women, and insulin sensitivity evaluated by euglycemic hyperinsulinemic
      clamp and homeostatic model assessment insulin resistance index (HOMA-IR). MAIN
      OUTCOME MEASURE(S): mRNA expression of adiponectin, leptin, and interleukin-6 (IL
      6) in adipose tissue, and plasma levels of leptin, adiponectin, resistin,
      visfatin, and tumor necrosis factor alpha (TNF-alpha). RESULT(S): The baseline
      data on body mass index (BMI), age, androgen levels, and insulin sensitivity was
      published previously. We found no independent effect of PCOS on the adipose
      expression of leptin, adiponectin, or IL-6 or on the plasma levels of
      adiponectin, leptin, resistin, visfatin, and TNF-alpha. Obesity was associated
      with increased mRNA expression of leptin, lower expression of adiponectin, and
      increased plasma levels of leptin. CONCLUSION(S): Obesity is per se associated
      with increased adipose expression and plasma levels of leptin, lower expression
      of adiponectin, and marginally elevated expression of IL-6, but PCOS does not
      appear to have an independent effect on the adipose expression of leptin,
      adiponectin, and IL-6 or the circulating adipocytokines. CLINICAL TRIAL
      REGISTRATION NUMBER: NCT00975832.

PMID- 22607893
TI  - Development of a vaccine against serogroup B has been the main scientific
      challenge. Preface.

PMID- 22607894
TI  - History of meningococcal vaccines and their serological correlates of protection.
AB  - For over a hundred years Neisseria meningitidis has been known to be one of the
      major causes of bacterial meningitis. However, effective vaccines were not
      developed until the latter part of the 20th century. The first of these were
      based on purified high molecular weight capsular polysaccharides and more
      recently the development of glycoconjugate vaccines has made paediatric
      immunisation programmes possible. The prevention of group B meningococcal disease
      has remained a challenge throughout this period. This review charts the history
      of the development of meningococcal vaccines and the importance of serological
      correlates of protection in their evaluation.

PMID- 22607895
TI  - Meningococcal vaccine development--from glycoconjugates against MenACWY to
      proteins against MenB--potential for broad protection against meningococcal
      disease.
AB  - Novartis Vaccines has a long-standing research and development interest in the
      prevention of invasive meningococcal disease. From the initial licensure of the
      monovalent meningococcal C glycoconjugate vaccine, Menjugate((r)), in response to
      the emergence of a virulent serogroup C ST-11 strain in the United Kingdom to the
      more recent development and licensure of a quadrivalent meningococcal ACWY
      glycoconjugate vaccine, Menveo((r)), Novartis has a continuing commitment to the
      development of more effective tools for the control of meningococcal disease.
      Menveo is now licensed for use in adolescents and adults in over 50 countries and
      results from phase III studies have shown the vaccine to be well-tolerated and
      highly immunogenic in infants with vaccination beginning from 2 months of age.
      The 'holy grail' of meningococcal disease control is a broadly protective vaccine
      against serogroup B (MenB), preferably a vaccine that protects all age groups
      including infants. As the serogroup B capsule is poorly immunogenic, efforts over
      the past 40 years have focused on identifying conserved proteins expressed on the
      bacterial surface that elicit bactericidal antibodies. Novartis has approached
      this problem utilizing genomic tools to identify proteins meeting these criteria
      in a process now known as 'reverse vaccinology'[1]. This process has resulted in
      a novel multicomponent MenB vaccine (4CMenB) that consists of four major
      immunogenic components (three subcapsular MenB protein antigens plus outer
      membrane vesicles (OMVs) which themselves provide multiple subcapsular antigens,
      the immunodominant one being PorA). These all induce bactericidal antibodies
      against the antigens that are important in determining the survival, function,
      and virulence of the meningococci. Phase II studies of 4CMenB have been completed
      and have demonstrated that the vaccine is highly immunogenic against reference
      meningococcal strains selected to support licensure. Post-vaccination sera from
      clinical studies have also been tested against a diverse panel of serogroup B
      strains to support the development of the Meningococcal Antigen Typing System
      (MATS), a tool used to predict vaccine strain coverage [2] This overview is
      intended to give a broad summary of the key clinical data derived from the Menveo
      and 4CMenB clinical development programs.

PMID- 22607896
TI  - Meningococcal disease: clinical presentation and sequelae.
AB  - The clinical spectrum of invasive meningococcal disease is diverse with
      meningitis and/or septicaemia being the commonest modes of presentation. The
      severity of manifestations of meningococcal infection ranges from bacteraemia,
      associated with mild non-specific symptoms, to fulminant sepsis with multiorgan
      failure and death in approximately 10-15% of cases. Localised infections (such as
      conjunctivitis or septic arthritis) as well as chronic disease may be the sole
      clinical manifestations but can also lead to disseminated fulminant disease.
      Among survivors, disabling long-term sequelae can complicate meningococcal
      disease and result in potentially devastating effects on the quality of life of
      survivors, most of whom are infants, children and adolescents. The only rational
      approach to the prevention of meningococcal disease and the associated human
      suffering is through vaccination.

PMID- 22607897
TI  - Meningococcal disease from the public health policy perspective.
AB  - The incidence and serogroup distribution of meningococcal disease vary by country
      and over time. In the United States, the annual incidence has been 0.5
      1.1/100,000 or about 1400-2800 cases annually with the highest incidence being in
      infants less than six months of age [1]. Given the availability of conjugate
      vaccines against serogroups A, C, W-135 and Y and the possible future
      availability of a group B vaccine, there is now the potential to effectively
      control meningococcal disease globally. The question then arises as to how public
      health policy can best serve this goal. MCV-D (Menactra) is not immunogenic in
      the first six months of life. For this reason, it has been proposed that
      immunization with this vaccine begin at nine months of age with a second dose at
      12 months. This proposal would rely upon indirect or "herd protection" to protect
      young infants with the highest disease incidence. A second vaccine, MCV-CRM
      (Menveo), is immunogenic in the first months of life and is under consideration
      by the FDA for use in infants two months of age and older. MCV-CRM could provide
      direct protection of this high risk group, but three primary doses plus a toddler
      booster are required for this approach. In developing public health
      recommendations to protect infants, policy makers must weigh the additional cost
      of immunizing with four doses versus the possibility that relying on herd
      protection using a lower cost immunization schedule beginning at nine months of
      age may leave young infants unprotected. Optimal control of meningococcal disease
      will require both the public will and public policy to best serve this goal. The
      decision as to what ages to target and which schedules to use should not only
      take into account the cost of the program, but also the severity of the disease
      and the high level public concern regarding meningococcal disease.

PMID- 22607898
TI  - Effectively introducing a new meningococcal A conjugate vaccine in Africa: the
      Burkina Faso experience.
AB  - A new Group A meningococcal (Men A) conjugate vaccine, MenAfriVacTM, was
      prequalified by the World Health Organization (WHO) in June 2010. Because Burkina
      Faso has repeatedly suffered meningitis epidemics due to Group A Neisseria
      meningitidis special efforts were made to conduct a country-wide campaign with
      the new vaccine in late 2010 and before the onset of the next epidemic
      meningococcal disease season beginning in January 2011. In the ensuing five
      months (July-November 2010) the following challenges were successfully managed:
      (1) doing a large safety study and registering the new vaccine in Burkina Faso;
      (2) developing a comprehensive communication plan; (3) strengthening the
      surveillance system with particular attention to improving the capacity for real
      time polymerase chain reaction (PCR) testing of spinal fluid specimens; (4)
      improving cold chain capacity and waste disposal; (5) developing and funding a
      sound campaign strategy; and (6) ensuring effective collaboration across all
      partners. Each of these issues required specific strategies that were managed
      through a WHO-led consortium that included all major partners (Ministry of
      Health/Burkina Faso, Serum Institute of India Ltd., UNICEF, Global Alliance for
      Vaccines and Immunization, Meningitis Vaccine Project, CDC/Atlanta, and the
      Norwegian Institute of Public Health/Oslo). Biweekly teleconferences that were
      led by WHO ensured that problems were identified in a timely fashion. The new
      meningococcal A conjugate vaccine was introduced on December 6, 2010, in a
      national ceremony led by His Excellency Blaise Compaore, the President of Burkina
      Faso. The ensuing 10-day national campaign was hugely successful, and over 11.4
      million Burkinabes between the ages of 1 and 29 years (100% of target population)
      were vaccinated. African national immunization programs are capable of achieving
      very high coverage for a vaccine desired by the public, introduced in a well
      organized campaign, and supported at the highest political level. The Burkina
      Faso success augurs well for further rollout of the Men A conjugate vaccine in
      meningitis belt countries.

PMID- 22607900
TI  - Considerations for controlling invasive meningococcal disease in high income
      countries.
AB  - The development of conjugate vaccines has enabled the prevention and control of
      Neisseria meningitidis caused by serogroups A, C, W-135 and Y. Vaccines that
      provide protection against a broad number of serogroup B strains likely will be
      available soon to enable greater control of meningococcal disease in high income
      countries. We present an argument for adequate post-marketing surveillance to
      monitor epidemiological shifts and to provide a context for the safety and
      reactogenicity of serogroup B vaccines, including the newer recombinant vaccines.
      We also offer a series of recommendations to address possible concerns about
      vaccine safety.

PMID- 22607899
TI  - Can we, should we, eradicate the meningococcus?
AB  - The eradication of infectious agents is an attractive means of disease control
      that, to date, has been achieved for only one human pathogen, the smallpox virus.
      The introduction of vaccines against Neisseria meningitidis into immunisation
      schedules, and particularly the conjugate polysaccharide vaccines which can
      interrupt transmission, raises the question of whether disease caused by this
      obligate human bacterium can be controlled, eliminated, or even eradicated. The
      limited number of meningococcal serogroups, lack of an animal reservoir, and
      importance of meningococcal disease are considerations in favour of eradication;
      however, the commensal nature of most infections, the high diversity of
      meningococcal populations, and the lack of comprehensive vaccines are all factors
      that suggest that this is not feasible. Indeed, any such attempt might be harmful
      by perturbing the human microbiome and its interaction with the immune system. On
      balance, the control and possible elimination of disease caused by particular
      disease-associated meningococcal genotypes is a more achievable and worthwhile
      goal.

PMID- 22607901
TI  - Can we defeat meningococcal disease in low and middle income countries?
AB  - The development of multivalent conjugate and protein-based meningococcal vaccines
      may make global control of meningococcal disease possible. However, achieving
      control of meningococcal disease in low and middle income countries will be
      challenging. In low income countries whose vaccination programmes receive
      financial support from the Global Alliance for Vaccination and Immunisation, the
      main challenge is lack of sufficient epidemiological information to allow
      rational decisions on vaccine introduction to be made and, in these countries,
      enhanced surveillance is needed. In middle income countries, financial challenges
      predominate. These could be met by demonstration of the cost effectiveness of new
      meningococcal vaccines and through the introduction of a tiered-pricing system.

PMID- 22607902
TI  - The use of vaccine antigen characterization, for example by MATS, to guide the
      introduction of meningococcus B vaccines.
AB  - Current concepts of vaccines against serogroup B meningococci (MenB) are mainly
      based on genetically variable protein antigens. Vaccine efficacy studies for
      meningococcal disease in developed countries are hampered by the low incidence.
      Licensure must therefore exclusively rely on clinical trials and laboratory
      investigation of meningococcal strains. In contrast to capsule polysaccharide
      vaccines, serum bactericidal assays for technical reasons are limited in their
      practicability as the surrogate of protection provided by MenB vaccines.
      Therefore, assays are required for reliable laboratory based assessment of
      expression of those specific antigen variants that are predicted to be targeted
      by bactericidal antibodies elicited by the vaccine. The MATS ELISA (MATS,
      meningococcal antigen typing system) reported recently is an example for such an
      assay. The paper discusses the pre- and post-licensure application of MATS, the
      role of reference laboratories, concepts of sustained provision of the assay,
      external quality assessment, and laboratory twinning.

PMID- 22607903
TI  - Future challenges in the elimination of bacterial meningitis.
AB  - Despite the widespread implementation of several effective vaccines over the past
      few decades, bacterial meningitis caused by Streptococcus pneumoniae, Haemophilus
      influenzae, Neisseria meningitidis and Group B Streptococcus (GBS) still results
      in unacceptably high levels of human mortality and morbidity. A residual disease
      burden due to bacterial meningitis is also apparent due to a number of persistent
      or emerging pathogens, including Mycobacterium tuberculosis, Escherichia coli,
      Staphylococcus aureus, Salmonella spp. and Streptococcus suis. Here, we review
      the current status of bacterial meningitis caused by these pathogens,
      highlighting how past and present vaccination programs have attempted to counter
      these pathogens. We discuss how improved pathogen surveillance, implementation of
      current vaccines, and development of novel vaccines may be expected to further
      reduce bacterial meningitis and related diseases in the future.

PMID- 22607905
TI  - Towards a meningitis free world--can we eliminate meningococcal meningitis?:
      contribution of the meningitis patient groups.
AB  - Patient groups play a critical part in the fight against meningitis in all its
      forms. The UK has the world's three largest meningitis patient groups, which over
      the past 3 decades have worked tirelessly in the fight against meningitis. Within
      the UK, where the patient groups work to prevent or alleviate the suffering
      caused by meningitis and septicaemia, their work is in three areas: continued
      research; demonstrating burden; and awareness-raising and advocacy. The research
      relates to developing and improving vaccines, and to improving outcomes for forms
      of meningitis that are not vaccine preventable. Demonstrating burden - showing
      the real impact of meningitis from a human perspective - highlights the need for
      vaccines to prevent the disease. Lives are saved by raising awareness of signs
      and symptoms and of the need for fast action, whilst advocacy can bring about
      change to improve the quality of life of those affected by meningitis. Awareness
      raising and advocacy also have the wider benefit of creating a climate in which
      people recognise the need for vaccines to prevent this dreadful disease. In
      addition, the patient groups seek to influence the early introduction and uptake
      of vaccines as they are licensed and approved by the expert bodies, the UK body
      being the Joint Committee for Vaccination and Immunisation (JCVI). Each area of
      activity is explored, and examples given from each of the patient groups of work
      they have done or are doing in that area.

PMID- 22607906
TI  - The association between the triglyceride to high-density lipoprotein cholesterol
      ratio with insulin resistance (HOMA-IR) in the general Korean population: based
      on the National Health and Nutrition Examination Survey in 2007-2009.
AB  - AIMS: This study explores the association between the ratio of triglyceride (TG)
      and high-density lipoprotein cholesterol (HDL-C) and insulin resistance according
      to waist circumference in the general Korean population. METHODS: 7623
      participants were selected from the Korean National Health and Nutrition
      Examination Survey (KNHANES) conducted during 2007-2009 and included in this
      cross-sectional study. Insulin resistance was defined as the values equal to or
      greater than the 75th percentile of the homeostasis model assessment of insulin
      resistance (HOMA-IR). RESULTS: Positive correlation was found between the ratio
      of TG and HDL-C and other variables such as waist circumference, total
      cholesterol, and HOMA-IR for both men and women. The odds ratios (ORs) (95%
      confidence interval) for insulin resistance for the highest quartile of TG/HDL-C
      were 2.48 in men and 3.05 in women. The significant relationship between the
      TG/HDL-C ratio and insulin resistance was not only maintained across all
      quartiles of waist circumference but also seemed to be enhanced in the higher
      quartiles of waist circumference. CONCLUSION: In the general Korean population,
      there seems to be a linear association between TG/HDL-C ratio and insulin
      resistance, regardless of degrees of waist circumference.

PMID- 22607904
TI  - The new multicomponent vaccine against meningococcal serogroup B, 4CMenB:
      immunological, functional and structural characterization of the antigens.
AB  - Neisseria meningitidis is a major cause of endemic cases and epidemics of
      meningitis and devastating septicemia. Although effective vaccines exist for
      several serogroups of pathogenic N. meningitidis, conventional vaccinology
      approaches have failed to provide a universal solution for serogroup B (MenB)
      which consequently remains an important burden of disease worldwide. The advent
      of whole-genome sequencing changed the approach to vaccine development, enabling
      the identification of potential vaccine candidates starting directly with the
      genomic information, with a process named reverse vaccinology. The application of
      reverse vaccinology to MenB allowed the identification of new protein antigens
      able to induce bactericidal antibodies. Three highly immunogenic antigens (fHbp,
      NadA and NHBA) were combined with outer membrane vesicles and formulated for
      human use in a multicomponent vaccine, named 4CMenB. This is the first MenB
      vaccine based on recombinant proteins able to elicit a robust bactericidal immune
      response in adults, adolescents and infants against a broad range of serogroup B
      isolates. This review describes the successful story of the development of the
      4CMenB vaccine, with particular emphasis on the functional, immunological and
      structural characterization of the protein antigens included in the vaccine.

PMID- 22607907
TI  - [Inferior vena cava leiomyosarcoma with liver metastasis. Multi-organ resection
      with vascular reconstruction].

PMID- 22607908
TI  - Biomechanical effect of rotator cuff augmentation with an acellular dermal matrix
      graft: a cadaver study.
AB  - BACKGROUND: Acellular human dermal matrix grafts (Graftjacket; Wright Medical
      Technology, Arlington, TN, USA) are used clinically for rotator cuff augmentation
      without a detailed understanding of their biomechanical effects. The purpose of
      this study was to evaluate the effect of augmentation with dermal grafts on the
      biomechanical effects of rotator cuff repairs. METHODS: Nine matched pairs of
      human cadaveric shoulders were used. A single-row rotator cuff repair combined
      with an augmentation graft was performed on one shoulder, and a single-row repair
      was performed on the contralateral shoulder as a control. An acellular dermal
      matrix graft was sutured to the tendon medially and fixed to the humerus
      laterally. The constructs were preloaded at 10 N and then cyclically loaded
      between 10 and 180 N for 1000 cycles, followed by tensile testing to failure at
      1.0 mm/s. FINDINGS: The maximum load of the augmentation group (560.2 N, SD 95.5)
      was greater than that of the control group (345.7 N, SD 60.8), while the linear
      stiffness of the augmentation group (65.2 N/mm, SD 15.6) was less than that of
      the control group (77.2 N/mm, SD 15.7). Reliable gap distance data were not
      obtained during cyclic loading in 5 of 9 augmented repairs due to the elasticity
      of the dermal matrix graft. INTERPRETATION: The dermal matrix graft augmentation
      increased the maximum load but did not increase the linear stiffness. The
      elasticity of the dermal matrix graft affected the biomechanical effects of the
      augmented rotator cuff repairs.

PMID- 22607909
TI  - [The law number 2005-370 of April 22, 2005 concerning the patients' rights at the
      end-of-life: improvement of the withholding and withdrawing treatment decision
      making process by an educational program. A monocenter prospective and
      retrospective pilot study].
AB  - OBJECTIVE: To assess the impact of an educational program on the quality of the
      end-of-life decision (EOLD). METHODS: Prospective study for 3 months in a
      surgical Intensive Care Unit (ICU) involving: staff training conferences and
      guidelines for documenting level-of-care staff conference; audit before and at 3
      months; analysis of records for deceased patients. The main outcome measures the
      proportion of treatment-limitation in dying ICU patients; and the secondary
      outcomes the decision-making process and nurses' satisfaction. RESULTS: Eighty
      three patients were included; among them, 14 with EOLD. Pre-death palliative
      strategy increased from 51 % to 85 % with a persisting improvement of practices
      after 2 years. All steps of EOLD decision-making processes were traced in all
      such cases, 85 % being based on the proposed guidelines. Nursing team's
      satisfaction rate almost doubled to 70 %. DISCUSSION: The study demonstrate staff
      members' capacity to quickly improve their procedures for palliative care when
      provided with appropriate tools to think about the process and come to a
      decision. Our data suggest the potential benefice to extend this program to the
      other specialties involved in the end-of-life process.

PMID- 22607910
TI  - Pleural intensity-modulated radiotherapy for malignant pleural mesothelioma.
AB  - PURPOSE: In patients with malignant pleural mesothelioma who are unable to
      undergo pneumonectomy, it is difficult to deliver tumoricidal radiation doses to
      the pleura without significant toxicity. We have implemented a technique of using
      intensity-modulated radiotherapy (IMRT) to treat these patients, and we report
      the feasibility and toxicity of this approach. METHODS AND MATERIALS: Between
      2005 and 2010, 36 patients with malignant pleural mesothelioma and two intact
      lungs (i.e., no previous pneumonectomy) were treated with pleural IMRT to the
      hemithorax (median dose, 46.8 Gy; range, 41.4-50.4) at Memorial Sloan-Kettering
      Cancer Center. RESULTS: Of the 36 patients, 56% had right-sided tumors. The
      histologic type was epithelial in 78%, sarcomatoid in 6%, and mixed in 17%, and
      6% had Stage I, 28% had Stage II, 33% had Stage III, and 33% had Stage IV. Thirty
      two patients (89%) received induction chemotherapy (mostly cisplatin and
      pemetrexed); 56% underwent pleurectomy/decortication before IMRT and 44% did not
      undergo resection. Of the 36 patients evaluable for acute toxicity, 7 (20%) had
      Grade 3 or worse pneumonitis (including 1 death) and 2 had Grade 3 fatigue. In 30
      patients assessable for late toxicity, 5 had continuing Grade 3 pneumonitis. For
      patients treated with surgery, the 1- and 2-year survival rate was 75% and 53%,
      and the median survival was 26 months. For patients who did not undergo surgical
      resection, the 1- and 2-year survival rate was 69% and 28%, and the median
      survival was 17 months. CONCLUSIONS: Treating the intact lung with pleural IMRT
      in patients with malignant pleural mesothelioma is a safe and feasible treatment
      option with an acceptable rate of pneumonitis. Additionally, the survival rates
      were encouraging in our retrospective series, particularly for the patients who
      underwent pleurectomy/decortication. We have initiated a Phase II trial of
      induction chemotherapy with pemetrexed and cisplatin with or without
      pleurectomy/decortication, followed by pleural IMRT to prospectively evaluate the
      toxicity and survival.

PMID- 22607911
TI  - Combined modality treatment for PET-positive non-Hodgkin lymphoma: favorable
      outcomes of combined modality treatment for patients with non-Hodgkin lymphoma
      and positive interim or postchemotherapy FDG-PET.
AB  - PURPOSE: To evaluate outcomes of patients treated for aggressive non-Hodgkin
      lymphoma (NHL) with combined modality therapy based on [(18)F]fluoro-2-deoxy-2-d
      glucose positron emission tomography (FDG-PET) response. METHODS AND MATERIALS:
      We studied 59 patients with aggressive NHL, who received chemotherapy and
      radiation therapy (RT) from 2001 to 2008. Among them, 83% of patients had stage
      I/II disease. Patients with B-cell lymphoma received R-CHOP (rituximab,
      cyclophosphamide, doxorubicin, vincristine, and prednisone)-based chemotherapy,
      and 1 patient with anaplastic lymphoma kinase-negative anaplastic T-cell lymphoma
      received CHOP therapy. Interim and postchemotherapy FDG-PET or FDG-PET/computed
      tomography (CT) scans were performed for restaging. All patients received
      consolidated involved-field RT. Median RT dose was 36 Gy (range, 28.8-50 Gy).
      Progression-free survival (PFS) and local control (LC) rates were calculated with
      and without a negative interim or postchemotherapy FDG-PET scan. RESULTS: Median
      follow-up was 46.5 months. Thirty-nine patients had negative FDG-PET results by
      the end of chemotherapy, including 12 patients who had a negative interim FDG-PET
      scan and no postchemotherapy PET. Twenty patients were FDG-PET-positive,
      including 7 patients with positive interim FDG-PET and no postchemotherapy FDG
      PET scans. The 3-year actuarial PFS rates for patients with negative versus
      positive FDG-PET scans were 97% and 90%, respectively. The 3-year actuarial LC
      rates for patients with negative versus positive FDG-PET scans were 100% and 90%,
      respectively. CONCLUSIONS: Patients who had a positive interim or
      postchemotherapy FDG-PET had a PFS rate of 90% at 3 years after combined modality
      treatment, suggesting that a large proportion of these patients can be cured with
      consolidated RT.

PMID- 22607912
TI  - Visual outcomes in pediatric optic pathway glioma after conformal radiation
      therapy.
AB  - PURPOSE: To assess visual outcome prospectively after conformal radiation therapy
      (CRT) in children with optic pathway glioma. METHODS AND MATERIALS: We used CRT
      to treat optic pathway glioma in 20 children (median age 9.3 years) between July
      1997 and January 2002. We assessed changes in visual acuity using the logarithm
      of the minimal angle of resolution after CRT (54 Gy) with a median follow-up of
      24 months. We included in the study children who underwent chemotherapy (8
      patients) or resection (9 patients) before CRT. RESULTS: Surgery played a major
      role in determining baseline (pre-CRT) visual acuity (better eye: P=.0431; worse
      eye: P=.0032). The visual acuity in the worse eye was diminished at baseline
      (borderline significant) with administration of chemotherapy before CRT (P=.0726)
      and progression of disease prior to receiving CRT (P=.0220). In the worse eye,
      improvement in visual acuity was observed in patients who did not receive
      chemotherapy before CRT (P=.0289). CONCLUSIONS: Children with optic pathway
      glioma initially treated with chemotherapy prior to receiving radiation therapy
      have decreased visual acuity compared with those who receive primary radiation
      therapy. Limited surgery before radiation therapy may have a role in preserving
      visual acuity.

PMID- 22607913
TI  - The inhibition of tumor growth and metastasis by self-assembled nanofibers of
      taxol.
AB  - Molecular hydrogels have big potential for local delivery and sustained release
      of therapeutic agents. In this paper, we reported on a molecular hydrogel mainly
      formed by the widely used anti-cancer drug of taxol. The hydrogel was formed by
      an ester bond hydrolysis process from a taxol derivative (Taxol-SA-GSSG, 1) and
      could be administrated into solid tumors to dramatically hinder their growths and
      prevent their metastasis. Besides the improved anti-cancer effect compared to the
      clinically used intravenous (i.v.) injection of Taxol((r)), the concentration of
      taxol in blood was low due to the local administration of taxol hydrogels, which
      greatly enhanced the dosage tolerance of mice to taxol and might reduce side
      effects of taxol during chemotherapy. Our observations suggested that the
      hydrogel mainly composed of taxol would have great potential for its practical
      applications.

PMID- 22607914
TI  - Role of physicochemical properties of coating ligands in receptor-mediated
      endocytosis of nanoparticles.
AB  - A fundamental understanding of the receptor-mediated endocytosis is of great
      importance in biomedicine. In this paper, we systematically investigate the
      effect of the properties of coating ligands on the cellular uptake of
      nanoparticles by using dissipative particle dynamics, and find that the strength
      of the receptor-ligand interaction, the ligand density and length as well as its
      rigidity can strongly affect the final equilibrium in the receptor-mediated
      endocytosis. Interestingly, it is found that the particle decorated with longer
      ligands is more likely to attach to the membrane, while it is harder to be
      totally engulfed. Increasing the ligand density and rigidity which enhances the
      uniform distribution of ligands on the particle may lead to the total engulfment.
      Further, we also show that the particle can be totally engulfed if one can
      reasonably design the hydrophobic/lipophobic properties of ligands. The present
      study shows that not only the chemical but also the physical parameters of
      ligands can govern the nanoparticle-cell interaction, which may give some
      significant insights into future nanoparticle design in drug delivery.

PMID- 22607916
TI  - Acute interstitial nephritis after amoxycillin with hematuria, red blood cell
      casts and hematuria-induced acute tubular injury.
AB  - A 62-year-old Caucasian man is described who developed acute kidney injury (AKI)
      and gross hematuria after a course with amoxycillin. At admission, urinalysis
      showed mild proteinuria, marked microscopic hematuria and cylindruria, which also
      included red blood cell casts. At renal biopsy an acute interstitial nephritis
      (AIN) was found, which was associated with many intratubular red blood cells and
      red blood cell casts, consequent acute tubular injury and red blood cell
      phagocytosis by tubular cells. After a course with corticosteroids, renal
      function partly recovered. This case demonstrates that red blood cell
      cylindruria, red blood cell intratubular casts and red blood cell-induced tubular
      injury can also be observed in patients with acute interstitial nephritis and not
      only in patients with glomerulonephritis as described so far. 

PMID- 22607915
TI  - The mental health of preschoolers in a Norwegian population-based study when
      their parents have symptoms of borderline, antisocial, and narcissistic
      personality disorders: at the mercy of unpredictability.
AB  - BACKGROUND: Clinical studies have shown that children of parents with mental
      health problems are most likely to develop psychiatric problems themselves when
      their parents have a Personality Disorder characterized by hostility. The
      Personality Disorders that appear most associated with hostility, with the
      potential to affect children, are Borderline Personality Disorder, Antisocial
      Personality Disorder and Narcissistic Personality Disorder. The question
      addressed in this study is whether the risk to children's mental health extends
      to the normal population of parents who have subclinical symptomlevels of these
      disorders. METHODS: This inquiry used data from a Trondheim, Norway community
      sample of 922 preschoolers and one parent for each child. The mean age of the
      children was 53 months (SD 2.1). Parents reported symptoms of Borderline,
      Antisocial and Narcissistic Personality Disorders on the DSM-IV ICD-10
      Personality Questionnaire, and the children's symptoms of DSM-IV behavioral and
      emotional diagnoses were measured with the Preschool Age Psychiatric Assessment,
      a comprehensive interview. Multigroup Structural Equation Modeling was used to
      assess the effect of parents' symptoms on their preschoolers' behavioral and
      emotional problems. RESULTS: The analyses yielded strongly significant values for
      the effect of parents' Personality Disorder symptoms on child problems,
      explaining 13.2% of the variance of the children's behavioral symptoms and 2.9%
      of the variance of internalizing symptoms. Biological parents' cohabitation
      status, i.e., whether they were living together, emerged as a strong moderator on
      the associations between parental variables and child emotional symptoms; when
      parents were not cohabiting, the variance of the children's emotional problems
      explained by the parents' Personality Disorder symptoms increased from 2.9% to
      19.1%. CONCLUSIONS: For the first time, it is documented that parents' self
      reported symptoms of Borderline, Antisocial, and Narcissistic Personality
      Disorders at a predominantly subclinical level had a strong effect on their
      children's psychiatric symptoms, especially when the biological parents were not
      living together. Child service providers need to be aware of these specific
      symptoms of parental Personality Disorders, which may represent a possible risk
      to children.

PMID- 22607917
TI  - Guest editorial. Conditions encountered at a level 1 trauma center:.

PMID- 22607918
TI  - Isolated superior orbital fissure syndrome resulting from gunshot wound to the
      head.

PMID- 22607919
TI  - Clival fracture with basilar artery laceration.

PMID- 22607920
TI  - Type I hangman's fracture.

PMID- 22607921
TI  - Simultaneous cases of traumatic coin aspiration.

PMID- 22607922
TI  - An isolated coracoid fracture.

PMID- 22607923
TI  - Manubrial fracture with an associated innominate artery injury.

PMID- 22607924
TI  - The wide mediastinum: don't forget about sternal fractures.

PMID- 22607925
TI  - Chronic posttraumatic pseudoaneurysm of the thoracic aorta.

PMID- 22607926
TI  - Upper thoracic spine fracture dislocation in a motorcyclist.

PMID- 22607927
TI  - Left hemidiaphragm rupture following high-speed motor vehicle crash.

PMID- 22607928
TI  - "Delayed" right diaphragmatic rupture because of positive pressure mechanical
      ventilation.

PMID- 22607929
TI  - Intussusception of a Meckel's diverticulum following blunt abdominal trauma.

PMID- 22607930
TI  - Delayed diagnosis of ureteral injury after gunshot wound to abdomen.

PMID- 22607931
TI  - Blunt urinary bladder trauma.

PMID- 22607932
TI  - Abdominal impalement from motor vehicle crash.

PMID- 22607933
TI  - Heterotopic ossification following a major traumatic event.

PMID- 22607935
TI  - Editors' Pick: Normal aging versus Alzheimer's disease - expression patterns may
      discern the differences.

PMID- 22607934
TI  - Loeffler's endocarditis in hypereosinophilic syndrome.

PMID- 22607937
TI  - Hydrogen-rich water prevents lipid deposition in the descending aorta in a rat
      periodontitis model.
AB  - OBJECTIVE: Periodontitis has been causally linked to atherosclerosis, which is
      mediated by the oxidative stress. As hydrogen-rich water (HW) scavenges reactive
      oxygen species (ROS), we hypothesized that HW could prevent lipid deposition
      induced by periodontitis in the aorta. The aim of this study was to investigate
      the effects of HW on the initiation of atherosclerosis in a rat periodontitis
      model. DESIGN: Eighteen 8-wk-old male Wistar rats were divided into three groups
      of six rats; the periodontitis group, periodontitis+HW group and the no treatment
      (control) group. In the periodontitis and periodontitis+HW groups, periodontitis
      was induced using a ligature for 4 wk, while the periodontitis+HW group was given
      water containing 800-1000 MUg/L hydrogen during the 4-wk experimental period.
      RESULTS: In the periodontitis group, lipid deposition in the descending aorta was
      observed. The periodontitis group also showed significant higher serum levels for
      ROS and oxidised low-density lipoprotein-cholesterol (ox-LDL) (1.7 and 1.4 times,
      respectively), and higher aortic expression levels of nitrotyrosine and hexanoyl
      lysine (HEL) (7.9 and 16.0 times, respectively), as compared to the control group
      (p<0.05). In the periodontitis+HW group, lipid deposition was lower. Lower serum
      levels of ROS and ox-LDL (0.46 and 0.82 times, respectively) and lower aortic
      levels of nitrotyrosine and HEL (0.27 and 0.19 times, respectively) were observed
      in the periodontitis+HW group than in the periodontitis group (p<0.05).
      CONCLUSIONS: HW intake may prevent lipid deposition in the rat aorta induced by
      periodontitis by decreasing serum ox-LDL levels and aortic oxidative stress.

PMID- 22607938
TI  - Immunomodulatory effect of the topical ophthalmic Janus kinase inhibitor
      tofacitinib (CP-690,550) in patients with dry eye disease.
AB  - OBJECTIVE: To evaluate the immunomodulatory effect of topical ophthalmic
      tofacitinib (CP-690,550) after an 8-week treatment period in patients with dry
      eye disease (DED). DESIGN: Biomarker substudy of a phase 1/2 prospective,
      randomized, vehicle- and comparator-controlled clinical trial (NCT00784719).
      PARTICIPANTS: A total of 82 patients with moderate to severe DED enrolled.
      METHODS: Patients received 1 of 5 doses of tofacitinib (0.0003%, 0.001%, 0.003%,
      or 0.005% twice daily [BID] or 0.005% once daily [QD]), active comparator
      (cyclosporine ophthalmic emulsion, 0.05% [Restasis, Allergan Inc., Irvine, CA]),
      or vehicle control BID for 8 weeks. Conjunctival impression cytology and tear
      fluid samples were collected at baseline and after an 8-week treatment period.
      Conjunctival cells were analyzed by flow cytometry for human leukocyte antigen DR
      1 (HLA-DR). Tear fluids were analyzed by microsphere-based immunoassays for tear
      levels of cytokines and inflammation markers. MAIN OUTCOME MEASURES: Reduction in
      inflammation assessed by change from baseline in conjunctival cell surface level
      of HLA-DR and tear level of cytokines and inflammation markers. RESULTS: At week
      8, a decrease in conjunctival cell surface expression of HLA-DR was observed in
      patients treated with tofacitinib 0.005% QD and 0.003% BID: 71% and 67% of
      baseline, respectively, compared with 133% of baseline in patients treated with
      vehicle (P=0.023 and P=0.006, compared with vehicle, respectively). Matrix
      metalloproteinase (MMP)-3 in tears was reduced from baseline at week 8 (40% of
      baseline, P=0.035) in the tofacitinib 0.005% QD group, whereas the vehicle group
      showed 77% of baseline (P>0.20). Interleukin (IL)-1beta in tears was 36% of
      baseline (P=0.053) in the tofacitinib 0.005% QD group and 95% of baseline (P >
      0.20) in the vehicle group. Several other cytokines and inflammation markers in
      tears, including MMP-9, IL-15, IL-17A, and IL-12p70, were markedly reduced in the
      tofacitinib 0.005% QD group but not the vehicle group. There was an association
      between the changes in HLA-DR and the tear inflammation markers (P<0.05): HLA-DR
      with IL-12p70 (r=0.49) and IL-1beta (r=0.46), IL-12p70 with IL-1beta (r=0.90),
      and IL-17A with MMP-9 (r=0.82). CONCLUSIONS: Topical ophthalmic tofacitinib may
      act as an immunomodulator in patients with DED. Treatment for 8 weeks showed a
      promising reduction of conjunctival cell surface HLA-DR expression and tear
      levels of proinflammatory cytokines and inflammation markers.

PMID- 22607939
TI  - Positive effect of a simplified diet on blood phenylalanine control in different
      phenylketonuria variants, characterized by newborn BH4 loading test and PAH
      analysis.
AB  - Until today, the mainstay of phenylketonuria (PKU) treatment is a phenylalanine
      (Phe)-restricted diet. Strict dietary treatment decreases flexibility and
      autonomy and still has a major impact on patients and their families. Compliance
      is often poor, particularly in adolescence. The aim of this study was to
      investigate the effect of the intake of fruits and vegetables containing Phe less
      than 100 mg/100g ('simplified diet'), as recommended by WHO for all individuals,
      instead of classical totally restricted diet on the course and treatment control
      of the disease in a well-characterized PKU cohort (n=80). All individual blood
      Phe measurements of each patient (1992-2009) were statistically analyzed before
      and after diet switch. Epidemiological data, age at diagnosis, PAH mutations,
      BH(4) responsiveness, as well as Phe control measurements and detailed diet
      information were tabulated in a local database. 62.5% had BH4 loading test and
      40% had PAH analysis; 50/80 switched from classical to simplified diet, including
      26 classical PKU, 13 moderate PKU, 7 mild PKU and 4 mild hyperphenylalaninemia
      (HPA). Median Phe levels on a simplified diet did not differ significantly to the
      median Phe levels on classical diet in all disease groups. Our results indicate
      that a simplified diet has no negative effect on blood Phe control in patients
      with hyperphenylalaninemia, independent of severity of the phenotype or the age
      at diet switch, over the period of 3 years. Thus, a simpler approach to dietary
      treatment of PKU available to all HPA patients is more likely to be accepted and
      adhered by patients and might also increase quality of life.

PMID- 22607940
TI  - Identification of a mutation in LARS as a novel cause of infantile hepatopathy.
AB  - Infantile hepatopathies are life-threatening liver disorders that manifest in the
      first few months of life. We report on a consanguineous Irish Traveller family
      that includes six individuals presenting with acute liver failure in the first
      few months of life. Additional symptoms include anaemia, renal tubulopathy,
      developmental delay, seizures, failure to thrive and deterioration of liver
      function with minor illness. The multisystem manifestations suggested a possible
      mitochondrial basis to the disorder. However, known causes of childhood liver
      failure and mitochondrial disease were excluded in this family by biochemical,
      metabolic and genetic analyses. We aimed to identify the underlying risk gene
      using homozygosity mapping and whole exome sequencing. SNP homozygosity mapping
      identified a candidate locus at 5q31.3-q33.1. Whole exome sequencing identified 1
      novel homozygous missense mutation within the 5q31.3-q33.1 candidate region that
      segregated with the hepatopathy. The candidate mutation is located in the LARS
      gene which encodes a cytoplasmic leucyl-tRNA synthetase enzyme responsible for
      exclusively attaching leucine to its cognate tRNA during protein translation.
      Knock-down of LARS in HEK293 cells did not impact on mitochondrial function even
      when the cells were put under physiological stress. The molecular studies confirm
      the findings of the patients' biochemical and genetic analyses which show that
      the hepatopathy is not a mitochondrial-based dysfunction problem, despite
      clinical appearances. This study highlights the clinical utility of homozygosity
      mapping and exome sequencing in diagnosing recessive liver disorders. It reports
      mutation of a cytoplasmic aminoacyl-tRNA synthetase enzyme as a possible novel
      cause of infantile hepatopathy and underscores the need to consider mutations in
      LARS in patients with liver disease and multisystem presentations.

PMID- 22607941
TI  - Measuring inequalities in health: what do we know? What do we need to know?
AB  - We argue that policy analysis aiming at curving inequalities in health calls for
      a better understanding of what we know about its measurement pathways. Assuming
      that health is a good that individuals trade off against other goods, unavoidable
      health inequalities result when after controlling for unavoidable factors (e.g.,
      age and gender), differences in socioeconomic status of an individual
      systemically engender differences in health outcomes. However, the measurement of
      such inequality and underpinning reasons behind are not suggestive of a clear
      picture. In reviewing the literature, we conclude that it is unclear what the
      evidence suggests about the reasons for health inequalities as well as the best
      possible instruments to measure both inequality and socioeconomic health
      gradients. We provide an evaluation of the different sources of health inequity
      and we draw upon measurement issues and their policy significance.

PMID- 22607942
TI  - Trends in invasive infection with methicillin-resistant Staphylococcus aureus,
      Connecticut, USA, 2001-2010.
AB  - We examined trends in incidence of methicillin-resistant Staphylococcus aureus
      (MRSA) infections in Connecticut, with emphasis on 2007-2010, after legislation
      required reporting of hospital infections. A case was defined as isolation of
      MRSA from normally sterile body sites, classified after medical record review as
      hospital onset (HO), community onset, health care-associated community onset
      (HACO), or community-associated (CA). Blood isolates collected during 2005-2010
      were typed and categorized as community- or health care-related strains. During
      2001-2010, a total of 8,758 cases were reported (58% HACO, 31% HO, and 11% CA),
      and MRSA incidence decreased (p<0.05) for HACO and HO, but increased for CA.
      Significant 3- to 4-year period trends were decreases in all MRSA (-18.8%), HACO
      (-12.8%), HO (-33.2%), and CA (-12.7%) infections during 2007-2010, and an
      increase in CA infections during 2004-2006. Decreases in health care-related
      isolates accounted for all reductions. Hospital infections reporting may have
      catalyzed the decreases.

PMID- 22607943
TI  - Radiologic findings of mesothelioma at the tunica vaginalis.
AB  - Malignant mesothelioma of the tunica vaginalis testis is a rare, but often fatal,
      malignancy that usually appears during the fourth decade and has a strong
      relationship with occupational exposure to asbestos and long-lasting hydrocele.
      We present a case involving a 36-year-old man without a history of hydrocele,
      trauma, or exposure to asbestos who developed malignant mesothelioma.

PMID- 22607944
TI  - Left laparoscopic radical nephrectomy in the presence of a duplicated inferior
      vena cava with complicated anomalous tributaries by a transmesocolic approach.
AB  - Laparoscopic radical nephrectomy should be executed under the most fundamental
      principle of early ligature of the renal artery to prevent diffusion of cancerous
      cells. This is extremely true in the treatment of large renal tumors touching the
      main renal vasculature. Obviously, the concomitance of a duplicated inferior vena
      cava (IVC) with associated aberrant tributaries will significantly increase the
      surgical difficulty and the procedural risk of vascular injury. Herein we
      describe a transperitoneal left laparoscopic radical nephrectomy for a large
      hilar left renal tumor in the presence of a duplicated IVC with complicated
      anomalous tributaries by a transmesocolic approach.

PMID- 22607945
TI  - How does the presence of antenatally detected caliectasis predict the risk of
      postnatal surgical intervention?
AB  - OBJECTIVE: To determine the effect of antenatally detected caliectasis on the
      postnatal surgical intervention rate. METHODS: From 2006 to 2010, 56 patients
      with an anteroposterior diameter (APD) of 7-20 mm on the prenatal ultrasound scan
      performed in the third trimester of pregnancy were included in the present study.
      In these 56 patients, other anomalies (vesicoureteral reflux, posterior urethral
      valves, duplex system, megaureter) were excluded, and the postnatal clinical and
      radiologic follow-up data were available. The mean follow-up was 12.82 +/- 10.72
      months. These 56 patients were divided into 2 groups: those with (n = 32) and
      without (n = 24) caliectasis. In the caliectasis group, the mean follow-up was
      13.6 +/- 12.09 months and was 11.7 +/- 8.70 months in the group without
      caliectasis. The statistical correlation between the postnatal operation rates
      and the presence of caliectasis (APD range 7-20 mm in third trimester) was
      investigated using the chi-square test. RESULTS: In the study group (n = 56) with
      an APD range of 7-20 mm in the third trimester, postnatal surgical treatment
      (pyeloplasty) was performed in 12 (37.5%) and 3 (12.5%) of the children with and
      without caliectasis, respectively (P = .037). The risk of postnatal surgical
      treatment increased threefold in patients with an APD of 7-20 mm and a diagnosis
      of caliectasis (relative risk 3.0, 95% confidence interval 1.07-8.40).
      CONCLUSION: In our study, the presence of concomitant caliectasis within the APD
      range of 7-20 mm on the third trimester ultrasound scan increased the risk of
      surgical treatment threefold. During prenatal counseling, the presence of
      caliectasis requires more rigorous follow-up.

PMID- 22607946
TI  - Editorial comment.

PMID- 22607947
TI  - Hypertension secondary to reninoma treated with laparoscopic nephron-sparing
      surgery in a child.
AB  - Reninoma is an extremely rare, renin-secreting, benign kidney tumor that can
      cause hypertension. We present a case of hypertension secondary to reninoma
      treated with laparoscopic nephron-sparing surgery in a 15-year-old girl and
      review some relevant published literature. Laparoscopic retroperitoneal nephron
      sparing surgery was performed and the tumor was removed intact. The
      histopathologic examination showed the characteristic of reninoma with positive
      CD34 staining immunohistochemically. The patient's blood pressure and level of
      serum potassium remained normal at 1-month follow-up examination.

PMID- 22607948
TI  - Circulating angiostatin, bFGF, and Tie2/TEK levels and their prognostic impact in
      bladder cancer.
AB  - OBJECTIVE: To assess the role and prognostic significance of angiostatin, basic
      fibroblast growth factor (bFGF), and tyrosine endothelial kinase (TEK/Tie2) in
      transitional cell bladder carcinoma. MATERIALS AND METHODS: Angiostatin, bFGF,
      and TEK serum concentrations were measured in 82 bladder cancer patients and 20
      age-matched healthy controls using enzyme-linked immunosorbent assay. Results
      were compared with clinicopathologic and follow-up data with the Mann-Whitney U
      test and Kaplan-Meier, univariate and multivariate Cox regression analyses.
      RESULTS: We found significantly decreased angiostatin and TEK serum levels and
      mildly elevated bFGF concentrations in samples of bladder cancer patients
      compared with controls (P < .001, P < .001, and P = .083, respectively).
      Furthermore, high TEK serum levels were correlated with poor disease-specific and
      metastasis-free survival in muscle-invasive bladder cancer (P = .013, P = .018),
      whereas angiostatin and bFGF concentrations did not show any correlation with
      patients' prognosis. Multivariate analysis revealed high TEK levels (<1.60 ng/mL)
      as borderline significant independent risk-factor of disease-specific survival
      (HR 1.83, 95% CI 0.97-3.44, P = .061) and metastasis-free survival (HR 2.65, 95%
      CI 0.93-7.55, P = .069). CONCLUSION: The characteristic differences in the
      circulating levels of angiostatin, TEK, and bFGF between patients and controls,
      suggest the presence of a tumor-induced proangiogenic milieu in bladder cancer.
      Serum TEK levels may contribute to a more reliable preoperative risk
      stratification in muscle-invasive bladder cancer and therefore may help to
      optimize therapeutic decisions.

PMID- 22607949
TI  - Is near infrared fluorescence imaging using indocyanine green dye useful in
      robotic partial nephrectomy: a prospective comparative study of 94 patients.
AB  - OBJECTIVE: To compare a consecutive prospective cohort of patients who underwent
      robotic partial nephrectomy (RPN) with near infrared fluorescence (NIRF) imaging
      with indocyanine green dye (ICG) with a previous consecutive patient cohort.
      METHODS: A total of 47 consecutive patients with renal masses suspicious for
      malignancy undergoing RPN were given 5-7.5 mg of ICG before hilar clamping or
      tumor excision. This cohort of patients was compared with 47 immediate previous
      consecutive patients who had undergone RPN without NIRF real-time imaging using
      ICG. The intraoperative, perioperative, and postoperative parameters were
      collected in an institutional review board-approved prospective database.
      RESULTS: The preoperative demographics and tumor complexity according to the
      nephrometry or preoperative aspects and dimensions used for an anatomic (PADUA)
      scores were similar. The mean warm ischemia time was significantly decreased in
      the ICG group (15 vs 17 minutes, P = .01). The median hospital stay was 2 days in
      both groups. No significant difference was seen in the positive margin rate (ICG,
      6% vs control, 8.5%; P = .69) or observed Clavien grade III-IV complications in
      these 2 cohorts (ICG, 4% vs control, 15%; P = .07). No adverse events were
      associated with ICG dye administration. Differential ICG uptake was observed with
      selective clamping or in patients with cystic tumors, hypofluorescent tumors with
      exophytic components, and angiomyelolipomas, but these benefits could not be
      quantified. NIRF-ICG was transiently helpful to identify the vascular anatomy and
      not helpful at all for endophytic tumors. CONCLUSION: RPN using NIRF-ICG can be
      performed safely and effectively. A decreased warm ischemia time in the ICG
      cohort was observed without specific measured advantages. Differential ICG uptake
      by different tumors did not lead to significant differences in the positive
      margin rate.

PMID- 22607950
TI  - Effect of hyperglycemia on expression of aquaporins in the rat vagina.
AB  - OBJECTIVE: To investigate the effect of hyperglycemia on the expression of the
      aquaporin (AQP) isoforms in the diabetic rat vagina. METHODS: Female Sprague
      Dawley rats (230-240 g, n = 45) were divided into control (n = 10) and
      experimental (n = 35) groups. Diabetes in the experimental group was induced by
      intraperitoneal injection of streptozotocin (STZ, 65 mg/kg). STZ-induced diabetic
      rats were left untreated or given subcutaneous injections of insulin (3 U/d).
      After 2 and 4 weeks, the blood glucose was measured, and the vaginal blood flow
      was assessed by Doppler flowmetry. The expression and cellular localization of
      AQP1 and AQP2 in the rat vagina were determined by Western blot and
      immunohistochemistry. RESULTS: The vaginal blood flow (mL/min/100 g tissue) after
      pelvic nerve stimulation was significantly lower in the STZ-induced diabetic rats
      (21.9 +/- 6.5 at 2 weeks and 21 +/- 2.8 at 4 weeks) compared with the control
      group (55.5 +/- 8.9 at 2 weeks and 52.9 +/- 6.5 at 4 weeks; P < .05). In
      contrast, the vaginal blood flow response was significantly greater in the
      insulin-treated diabetic groups (47.7 +/- 8.7 at 2 weeks and 47.7 +/- 8.4 at 4
      weeks) and comparable to that of the control group. The protein expression of
      AQP2 was significantly lower in the STZ-induced diabetic rats and was restored to
      the control level after insulin treatment. However, no change was seen in AQP1
      expression. Thus, hyperglycemia might cause downregulation of AQP2 expression in
      the diabetic rat vagina. CONCLUSION: These results suggest that decreased vaginal
      lubrication in diabetic women might result from changes in aquaporin expression,
      in addition to a reduction in the vaginal blood flow response.

PMID- 22607952
TI  - Editorial comment.

PMID- 22607953
TI  - Research into the structure of the kidney glomerulus--making it count.
AB  - The renal glomerulus and its components have been intensively studied using
      microscopy - both light and electron - for decades and much has been learnt about
      their role in the pathogenesis of chronic kidney diseases such as diabetic
      nephropathy. In order to get more than purely qualitative information from the
      images, stereological tools have been applied to obtain unbiased quantitative
      data and thus allow structural-functional relationships to be explored. These
      techniques are likely to continue to be used in the coming decades in order to
      provide vital information about the disease process, complementing knowledge
      obtained from molecular techniques.

PMID- 22607956
TI  - Cloud computing and virtualization technology in radiology.

PMID- 22607954
TI  - Transition to retirement and risk of cardiovascular disease: prospective analysis
      of the US health and retirement study.
AB  - Transitioning from work to retirement could be either beneficial or harmful for
      health. We investigated the association between transition to retirement and risk
      of stroke and myocardial infarction (MI). We followed US Health and Retirement
      Study participants age 50+ working full-time for pay and free of major
      cardiovascular disease (n = 5422) in 1998 up to 10 years for transition to full
      retirement and self- or proxy-report of either stroke or MI (CVD; 665 events). We
      used discrete-time survival analysis to compare the CVD incidence for the fully
      retired versus the full-time working population. To distinguish short-term from
      long-term risks, we compared the association in the first year after retirement
      to estimates 2+ years after retirement. In the full model adjusting for age, sex,
      childhood and adult SES, behavior, and co-morbidities, being retired was
      associated with elevated odds of CVD onset (OR = 1.40, 95% CI: 1.04, 1.90)
      compared to those remaining in the full-time labor force. The odds ratio for CVD
      incidence within the first year of retirement was 1.55 (95% CI: 1.03, 2.33). From
      the second year post-retirement and thereafter, the retired had marginally
      elevated risk of CVD compared to those still working (OR = 1.35; 95% CI: 0.96,
      1.91). Although confidence intervals were wide for some sub-groups, there were no
      significant interactions by sex or socioeconomic status. Results suggest that CVD
      risk is increased after retirement.

PMID- 22607957
TI  - [Treatment of recurrent pulmonary tuberculosis].
AB  - INTRODUCTION: Tuberculosis (TB) is a greatest public health problem of the world.
      This work aims to study the antituberculous treatment and the evolution of the
      patients with recurrent tuberculosis. PATIENTS AND METHOD: The study is a
      retrospective study on 64 patients with recidivant pulmonary TB: A1 group: at the
      first TB attack; A2 group: at the time of recidivant TB, and 105 controls
      patients with confirmed TB without recidive. RESULTS: Multidrug-resistant TB is
      more frequent with recidivant TB (21.1% vs 3%, P<0.05) and also extensively drug
      resistant. Antituberculous treatment duration in group A1, A2 and T was
      respectively 8.63 months, 9.79 months, and 7.08 months. Antituberculous drug
      complications were more frequent in group A2 compared to group T (76.1% vs 41.2%;
      P<0.001). CONCLUSION: All tuberculous patients, specially recidivant TB, should
      benefit of particular care and drug protocol adaptation.

PMID- 22607958
TI  - Sequence variants of allele 22 and 23 of DYS635 causing different stutter rates.

PMID- 22607959
TI  - Treatment of chronic myelomonocytic leukemia with 5-Azacitidine: a case series
      and literature review.
AB  - Chronic myelomonocytic leukemia (CMML) is a clinically heterogeneous disease,
      with no standard treatment. We present the outcome of ten patients diagnosed with
      CMML and treated with AZA in our institutions between 2005 and 2010. All patients
      were transfusion dependent at the time of initiation of therapy. The overall
      response rate was 60%. Responses were obtained in 2/3 of the patients with
      proliferative CMML. The median survival from start of therapy was 20 months. AZA
      treatment was well-tolerated and associated with a significant response rate in
      all forms of the disease.

PMID- 22607960
TI  - Targeting cyclin D1 for high risk myelodysplastic syndromes.

PMID- 22607961
TI  - Local transmission of imported endemic syphilis, Canada, 2011.
AB  - Endemic (nonvenereal) syphilis is relatively common in nonindustrialized regions
      of the world. We describe a case of local transmission in Canada and review tools
      available for confirming a diagnosis. Improved molecular tools and global
      clinical awareness are needed to recognize cases of endemic syphilis imported to
      areas where it is not normally seen.

PMID- 22607963
TI  - Ongoing mumps outbreak in Novi Sad, the autonomous province of Vojvodina, Serbia,
      January to April 2012.
AB  - From 16 January to 30 April 2012, a total of 119 cases of mumps were notified in
      Novi Sad, Serbia. Of these cases, 89 (75%), were among students. The average age
      of cases was 22 years-old (range 3-37). The outbreak is still ongoing in Novi Sad
      and is spreading to other parts of the Vojvodina province. As of 30 April, 209
      cases have been notified in the province among those 119 from Novi Sad.

PMID- 22607962
TI  - Role of MicroRNAs in lung disease.
AB  - MicroRNAs (miRNAs) are small non-coding RNA molecules that negatively regulate
      gene expression. They actively participate in the modulation of important cell
      physiological processes and are involved in the pathogenesis of lung diseases
      such as lung cancer, pulmonary fibrosis, asthma and chronic obstructive pulmonary
      disease. A better understanding of the role that miRNAs play in these diseases
      could lead to the development of new diagnostic and therapeutic tools. In this
      review, we discuss the role of some miRNAs in different lung diseases as well as
      the possible future of these discoveries in clinical applications.

PMID- 22607964
TI  - Age-dependent prevalence of antibodies cross-reactive to the influenza A(H3N2)
      variant virus in sera collected in Norway in 2011.
AB  - Antibody cross-reactivity to the influenza A(H3N2) variant virus recently
      reported in the United States, was investigated in Norwegian sera. Seroprevalence
      was 40% overall, and 71% in people born between 1977 and 1993. The most
      susceptible age groups were children and people aged around 50 years. The high
      immunity in young adults is likely to be due to strong priming infection with
      similar viruses in the 1990s. More research is needed to explain the poor
      immunity in 45-54 year-olds.

PMID- 22607965
TI  - Fatal case of human rabies imported to Italy from India highlights the importance
      of adequate post-exposure prophylaxis, October 2011.
AB  - In October 2011, an Indian man resident in Italy was admitted to a hospital in
      Mantua, Italy with symptoms of acute encephalitis. Due to a recent history of
      bite by a suspected rabid dog in India, where he had received incomplete post
      exposure treatment, rabies was suspected. The patient died after 22 days of
      intensive care treatment and rabies was confirmed post mortem. This report
      stresses the need of appropriate post-exposure prophylaxis in rabies-endemic
      countries.

PMID- 22607966
TI  - Case registry systems for pandemic influenza A(H1N1)pdm09 in Europe: are there
      lessons for the future?
AB  - Countries across Europe developed a range of database systems to register
      pandemic influenza A(H1N1)pdm09 cases. Anecdotal reports indicate that some
      systems were not as useful as expected. This was a cross-sectional, semi
      structured survey of health professionals who collected and reported pandemic
      influenza A(H1N1)pdm09 cases in 23 countries within the 27 European Union (EU)
      Member States plus Norway. We describe here the experiences of using pandemic
      case register systems developed before and during the pandemic, whether the
      systems were used as intended and, what problems, if any, were encountered. We
      conducted the survey to identify improvements that could be made to future
      pandemic case registers at national and EU level. Despite many inter-country
      differences, 17 respondents felt that a standardised case register template
      incorporating a limited number of simple standard variables specified in advance
      and agreed between the World Health Organization and the European Centre for
      Disease Prevention and Control could be useful. Intra- and inter-country working
      groups could facilitate information exchange, clearer system objectives and
      improved interoperability between systems.

PMID- 22607967
TI  - The Munich Shoulder Questionnaire (MSQ): development and validation of an
      effective patient-reported tool for outcome measurement and patient safety in
      shoulder surgery.
AB  - BACKGROUND: Outcome measurement in shoulder surgery is essential to evaluate the
      patient safety and treatment efficiency. Currently this is jeopardized by the
      fact that most patient-reported self-assessment instruments are not comparable.
      Hence, the aim was to develop a reliable self-assessment questionnaire which
      allows an easy follow-up of patients. The questionnaire also allows the
      calculation of 3 well established scoring systems, i.e. the Shoulder Pain and
      Disability Index (SPADI), the Constant-Murley Score (CMS), and the Disabilities
      of the Arm, Shoulder and Hand (DASH) Score. The subjective and objective items of
      these three systems were condensed into a single 30-questions form and validated
      against the original questionnaires. METHODS: A representative collective of
      patients of our shoulder clinic was asked to fill in the newly designed self
      assessment Munich Shoulder Questionnaire (MSQ). At the same time, the established
      questionnaires for self-assessment of CONSTANT, SPADI and DASH scores were handed
      out. The obtained results were compared by linear regression analysis. RESULTS:
      Fifty one patients completed all questionnaires. The correlation coefficients of
      the results were r = 0.91 for the SPADI, r = -0.93 for the DASH and r = 0.94 for
      the CMS scoring system, respectively. CONCLUSIONS: We developed an instrument
      which allows a quantitative self-assessment of shoulder function. It provides
      compatible data sets for the three most popular shoulder function scoring systems
      by one single, short 30-item. This instrument can be used by shoulder surgeons to
      effectively monitor the outcome, safety and quality of their treatment and also
      compare the results to published data in the literature.

PMID- 22607968
TI  - Quantifying the exact allocation ratios in randomized clinical trials with biased
      coin randomization.
AB  - The biased coin randomization approach is frequently adopted in randomized
      clinical trials to control the balance in overall treatment assignments. In this
      article, an algorithm is developed to theoretically determine the exact
      allocation ratios for all the patients that will be enrolled in a randomized
      clinical trial with biased coin randomization based on the order in which they
      are randomized. Our results show that the exact allocation ratios can
      significantly deviate from the ratio as specified for the trial, which poses
      challenges to the enrollment of the trial and to the interpretation of the
      results. In order to maintain a constant allocation ratio throughout the trial, a
      modification of the widely adopted permuted block randomization is proposed,
      which is shown to achieve better balance for not only the overall treatment
      assignments but also the baseline stratification variables that are desired to be
      balanced at the end of the trial.

PMID- 22607969
TI  - Towards amino acid recommendations for specific physiological and patho
      physiological states in pigs.
AB  - The objective of this review is to provide an overview of the implication of
      amino acids (AA) in important physiological functions. This is done in the
      context of pig production where the competition for AA utilisation is exacerbated
      by constraints to maximise productive responses and the necessity to reduce
      dietary protein input for environmental, economic and sanitary issues. Therefore,
      there is an opportunity to refine the nutritional recommendations by exploring
      the physiological roles of AA. For example, methionine and cysteine, either in
      selenised or sulfur forms, are directly involved in the regulation of the
      glutathione antioxidative system. In sows, glutathione antioxidative system may
      contribute to improving ovulation conditions through control of oxidative
      pressure. Supplementation of sow diets with l-arginine, a precursor of NO and
      polyamines, may stimulate placental growth, promoting conceptus survival, growth
      and tissue development. The beneficial effect of arginine supplementation has
      been also suggested to improve lactation performance. Feed intake is usually the
      first response that is impacted by an inadequate AA supply. Valine and tryptophan
      imbalances may act as signals for decreasing feed intake. AA are also important
      nutrients for maintaining the animal's defence systems. Threonine, one of the
      main constituents of mucin protein, is important for gut development during the
      postnatal period. It may exert a protective effect that reduces the impact of
      weaning on gut morphology and associated disturbances. Finally, tryptophan is
      involved in the regulation of the defence system through its action as a
      precursor of antioxidants and its effect on the inflammatory response.

PMID- 22607970
TI  - How we currently choose to repair retinal detachment in the United States
      medicare population.

PMID- 22607971
TI  - Molecular epidemiology of geographically dispersed Vibrio cholerae, Kenya,
      January 2009-May 2010.
AB  - Numerous outbreaks of cholera have occurred in Kenya since 1971. To more fully
      understand the epidemiology of cholera in Kenya, we analyzed the genetic
      relationships among 170 Vibrio cholerae O1 isolates at 5 loci containing variable
      tandem repeats. The isolates were collected during January 2009-May 2010 from
      various geographic areas throughout the country. The isolates grouped genetically
      into 5 clonal complexes, each comprising a series of genotypes that differed by
      an allelic change at a single locus. No obvious correlation between the
      geographic locations of the isolates and their genotypes was observed.
      Nevertheless, geographic differentiation of the clonal complexes occurred. Our
      analyses showed that multiple genetic lineages of V. cholerae were simultaneously
      infecting persons in Kenya. This finding is consistent with the simultaneous
      emergence of multiple distinct genetic lineages of V. cholerae from endemic
      environmental reservoirs rather than recent introduction and spread by travelers.

PMID- 22607972
TI  - Effect of maternal dietary energy types on placenta nutrient transporter gene
      expressions and intrauterine fetal growth in rats.
AB  - OBJECTIVE: The objectives of this study were to investigate the effects of
      maternal dietary energy types on the mRNA expressions of the placental nutrient
      transporter and intrauterine fetal growth and to examine whether altered
      intrauterine fetal growth could be associated with different gene expressions
      relating to fetal energy metabolism and DNA methylation. METHODS: Seventy-two 3
      mo-old rats were allocated to one of four groups: low fat/low fiber (L-L), low
      fat/high fiber, high fat/low fiber (H-L), or high fat/high fiber. Rats were fed
      the treatment diets 4 wk before mating and continued in pregnancy until sample
      collections were obtained on days 13.5 and 17.5 of pregnancy. RESULTS: The fetal
      weight in the L-L group was significantly lower than that in the H-L group (P <
      0.05). The placental nutrient transporter mRNA expressions of glucose transporter
      3 (Slc2a3) and cationic amino acid transporter-1 (Slc7a1) in the L-L group with a
      decreased fetal weight were downregulated compared with that in the H-L group
      with an increased fetal weight. However, placental Slc2a1 and the system A amino
      acid transporter gene Slc38a4 mRNA expressions were adaptively upregulated by the
      L-L diet with a decreased fetal weight (P < 0.05). For the placental imprinted
      gene Igf-2 and H19 expressions, lower Igf-2 and higher H19 expressions were
      associated with the decreased fetal growth in the L-L group compared with the H-L
      group with an increased fetal weight. Different fetal growth was associated with
      different DNA methyltransferase-1 and methyltransferase-3a expressions (P > 0.05)
      and energy metabolism-related genes. CONCLUSION: Collectively, these results
      demonstrated that intrauterine fetal growth could be affected by different energy
      intake types through placenta nutrient transporter gene expressions, and
      different fetal growths were associated with altered fetal genes related to DNA
      methylation and energy metabolism.

PMID- 22607973
TI  - Hydrogen(H2) treatment for acute erythymatous skin diseases. A report of 4
      patients with safety data and a non-controlled feasibility study with H2
      concentration measurement on two volunteers.
AB  - BACKGROUND: We have treated 4 patients of acute erythematous skin diseases with
      fever and/or pain by H2 enriched intravenous fluid. We also added data from two
      volunteers for assessing the mode of H2 delivery to the skin for evaluation of
      feasibility of H2 treatment for this type of skin diseases. METHODS: All of the
      four patients received intravenous administration of 500 ml of H2 enriched fluid
      in 30 min for more than 3 days except in one patient for only once. From two
      volunteers (one for intravenous H2 administration and the other for H2
      inhalation), blood samples were withdrawn serially and air samples were collected
      from a heavy duty plastic bag covering a leg, before, during and after H2
      administration. These samples were checked for H2 concentration immediately by
      gas chromatography. Multiple physiological parameters and blood chemistry data
      were collected also. RESULTS: Erythema of these 4 patients and associated
      symptoms improved significantly after the H2 treatment and did not recur.
      Administration of H2 did not change physiological parameters and did not cause
      deterioration of the blood chemistry. The H2 concentration in the blood from the
      volunteers rapidly increased with H2 inhalation and slowly decreased with
      cessation of H2 particularly in the venous blood, while H2 concentration of the
      air from the surface of the leg showed much slower changes even after H2
      inhalation was discontinued, at least during the time of sample collection.
      CONCLUSION: An improvement in acute erythemtous skin diseases followed the
      administration of H2 enriched fluid without compromising the safety. The H2
      delivery study of two volunteers suggested initial direct delivery and additional
      prolonged delivery possibly from a slowly desaturating reservoir in the skin to
      the surface.

PMID- 22607974
TI  - The ubiquitin ligase XIAP recruits LUBAC for NOD2 signaling in inflammation and
      innate immunity.
AB  - Nucleotide-binding and oligomerization domain (NOD)-like receptors constitute a
      first line of defense against invading bacteria. X-linked Inhibitor of Apoptosis
      (XIAP) is implicated in the control of bacterial infections, and mutations in
      XIAP are causally linked to immunodeficiency in X-linked lymphoproliferative
      syndrome type-2 (XLP-2). Here, we demonstrate that the RING domain of XIAP is
      essential for NOD2 signaling and that XIAP contributes to exacerbation of
      inflammation-induced hepatitis in experimental mice. We find that XIAP
      ubiquitylates RIPK2 and recruits the linear ubiquitin chain assembly complex
      (LUBAC) to NOD2. We further show that LUBAC activity is required for efficient NF
      kappaB activation and secretion of proinflammatory cytokines after NOD2
      stimulation. Remarkably, XLP-2-derived XIAP variants have impaired ubiquitin
      ligase activity, fail to ubiquitylate RIPK2, and cannot facilitate NOD2
      signaling. We conclude that XIAP and LUBAC constitute essential ubiquitin ligases
      in NOD2-mediated inflammatory signaling and propose that deregulation of NOD2
      signaling contributes to XLP-2 pathogenesis.

PMID- 22607976
TI  - STT3B-dependent posttranslational N-glycosylation as a surveillance system for
      secretory protein.
AB  - Nascent secretory proteins are extensively scrutinized at the endoplasmic
      reticulum (ER). Various signatures of client proteins, including exposure of
      hydrophobic patches or unpaired sulfhydryls, are coordinately utilized to reduce
      nonnative proteins in the ER. We report here the cryptic N-glycosylation site as
      a recognition signal for unfolding of a natively nonglycosylated protein,
      transthyretin (TTR), involved in familial amyloidosis. Folding and ER-associated
      degradation (ERAD) perturbation analyses revealed that prolonged TTR unfolding
      induces externalization of cryptic N-glycosylation site and triggers STT3B
      dependent posttranslational N-glycosylation. Inhibition of posttranslational N
      glycosylation increases detergent-insoluble TTR aggregates and decreases cell
      proliferation of mutant TTR-expressing cells. Moreover, this modification
      provides an alternative pathway for degradation, which is EDEM3-mediated N-glycan
      dependent ERAD, distinct from the major pathway of Herp-mediated N-glycan
      independent ERAD. Hence we postulate that STT3B-dependent posttranslational N
      glycosylation is part of a triage-salvage system recognizing cryptic N
      glycosylation sites of secretory proteins to preserve protein homeostasis.

PMID- 22607975
TI  - Clustered mutations in yeast and in human cancers can arise from damaged long
      single-strand DNA regions.
AB  - Mutations are typically perceived as random, independent events. We describe here
      nonrandom clustered mutations in yeast and in human cancers. Genome sequencing of
      yeast grown under chronic alkylation damage identified mutation clusters that
      extend up to 200 kb. A predominance of "strand-coordinated" changes of either
      cytosines or guanines in the same strand, mutation patterns, and genetic controls
      indicated that simultaneous mutations were generated by base alkylation in
      abnormally long single-strand DNA (ssDNA) formed at double-strand breaks (DSBs)
      and replication forks. Significantly, we found mutation clusters with analogous
      features in sequenced human cancers. Strand-coordinated clusters of mutated
      cytosines or guanines often resided near chromosome rearrangement breakpoints and
      were highly enriched with a motif targeted by APOBEC family cytosine-deaminases,
      which strongly prefer ssDNA. These data indicate that hypermutation via multiple
      simultaneous changes in randomly formed ssDNA is a general phenomenon that may be
      an important mechanism producing rapid genetic variation.

PMID- 22607977
TI  - Comparison of methods to determine sex by evaluating the greater sciatic notch:
      Visual, angular and geometric morphometrics.
AB  - Sex estimation is the first step for biological profile reconstruction of an
      unknown skeleton (archaeological or contemporary) and consequently for positive
      identification of skeletal remains recovered from forensic settings. Several
      tools have been developed using different osseous structures. With the intention
      to provide an objective method comparison, we reported the analysis of three
      different methods (visual, metric and geometric morphometrics) for sex assessment
      of the greater sciatic notch. One hundred and thirty pelvic bones (45.4% females
      and 54.6% males) from the National Autonomous University of Mexico Skeletal
      Collection pertaining to the contemporary Mexican population were analyzed. We
      used the ROC-analysis to test between desired false positive thresholds (1
      specificity) and expected true positive rates (sensitivity) in order to predict
      the best approach to sex assessment. The comparison of the area under the ROC
      curves shows significant differences among visual and metric methods. At the same
      time, the analysis suggested that higher morphological variation among the sexes
      is independent of the methodological approach. The results indicate that the
      metric (angle), with a high percent of indeterminate cases (34.6%), and visual,
      with 26.2% of the cases allocated as intermediate cases, were poorly accurate; we
      cannot recommend these techniques for sexing an unknown specimen. On the other
      hand, the geometric morphometrics approach improves sex estimation in 82.3% of
      correctly classified individuals with more than 95% of posterior probability. In
      addition to the method comparison, the major sexual variation of the greater
      sciatic notch was determined to be located on its posterior border.

PMID- 22607978
TI  - Detection of spermatozoa following consensual sexual intercourse.
AB  - INTRODUCTION: In cases of sexual assault, the finding of semen can provide
      crucial evidence. The presence of spermatozoa serves as proof of a sexual act and
      may give the identity of the alleged perpetrator through DNA-profiling. In most
      western countries, there are guidelines for standardized examinations of sexual
      assault victims. For an objective evaluation of the findings, substantial
      knowledge of aspects regarding consensual sexual intercourse is crucial. The aim
      of this study was to examine detection frequencies and genital sampling sites of
      spermatozoa following consensual sexual intercourse. METHODS: In a prospective
      setting, 60 women underwent forensic examination following consensual sexual
      intercourse. Specimens were obtained from the external genitalia, the posterior
      fornix and the cervical canal, and examined using the Papanicolau stain and
      standard light microscopy. RESULTS: We found that 88% of possible cases were
      positive for spermatozoa. The posterior fornix was significantly better than the
      other sites for detection of spermatozoa and the number of spermatozoa decreased
      significantly over time. In a large sub-group of women who reported that no intra
      vaginal ejaculation had taken place during their latest intercourse, a
      significant number (14%) had spermatozoa in the vagina. CONCLUSION: Spermatozoa
      were best recovered from the posterior fornix, but spermatozoa were also present
      on swabs taken from the external genitalia. Detection of spermatozoa is thus
      possible in cases where a speculum examination is denied.

PMID- 22607979
TI  - Quantitative immunohistochemical analysis of human brain basic fibroblast growth
      factor, glial fibrillary acidic protein and single-stranded DNA expressions
      following traumatic brain injury.
AB  - Previous studies demonstrated the healing process after traumatic brain injury
      (TBI), usually at the site or in the area adjacent to the injury, in connection
      with wound timing. However, the whole brain condition after TBI has not been
      elucidated clearly. In the present study, we investigated immunohistochemistry of
      the basic fibroblast growth factor (bFGF), glial fibrillary acidic protein (GFAP)
      and single-stranded DNA (ssDNA) in the parietal lobe and hippocampus distant from
      the primary injury site in forensic autopsy cases of TBI (n=174). Characteristic
      findings were detected with regard to brain compression signs and survival time
      (ST). Peracute deaths (n=22) had a lower GFAP positivity in the parietal white
      matter. Fatalities without a brain compression sign (parahippocampal
      herniation/Duret hemorrhage; n=53) had a lower brain weight without glial loss;
      however, GFAP positivity in the parietal white matter was decreased during ST of
      <12h, and glial bFGF positivity was increased at each site in deaths after 12h to
      3 days, followed by a delayed neuronal loss after 3 days. Fatalities with a brain
      compression sign (n=78) showed a higher brain weight, and gradual glial and
      neuronal losses with an early increase of glial bFGF positivity in the parietal
      cerebral cortex (ST <0.5h). This was followed by an increase of glial bFGF
      positivity in other sites (ST, 6-24h), and final decreases of glial bFGF and GFAP
      positivities with increased neuronal ssDNA positivity in the parietal lobe and
      hippocampus (ST >3 days), which were detected in earlier deaths despite
      decompressive craniectomy (ST, 12-60h; n=21). These observations suggest that the
      combined use of bFGF, GFAP and ssDNA immunohistochemistry can be used to evaluate
      the severity of damage and response of brain after TBI.

PMID- 22607980
TI  - Subdural hemorrhage: A unique case involving secondary vitamin K deficiency
      bleeding due to biliary atresia.
AB  - Extrahepatic biliary atresia (EHBA) is a rare disease characterized by
      progressive and obliterative cholangiopathy in infants and is one of the major
      causes of secondary vitamin K deficiency bleeding (VKDB) due to cholestasis
      induced fat malabsorption. Breast feeding increases the tendency of bleeding in
      EHBA patients because breast milk contains low amounts of vitamin K. A 2-month
      old female infant unexpectedly died, with symptoms of vomiting and jaundice prior
      to death. She had been born by uncomplicated vaginal delivery and exhibited
      normal growth and development with breastfeeding. There was no history of trauma.
      She received vitamin K prophylaxis orally. In an emergency hospital, a CT scan
      showed a right intracranial hematoma and mass effect with midline shift to the
      left. In the postmortem examination, severe atresia was observed in the whole
      extrahepatic bile duct. Histologically, cholestasis, periductal fibrosis, and
      distorted bile ductules were noted. The gallbladder was not identified. A
      subdural hematoma and cerebellar tonsillar herniation were found; however, no
      traumatic injury in any part of the body was observed. Together, these findings
      suggest that the subdural hemorrhage was caused by secondary vitamin K deficiency
      resulting from a combination of cholestasis-induced fat malabsorption and
      breastfeeding. Subdural hemorrhage by secondary VKDB sometimes occurs even when
      vitamin K prophylaxis is continued. This case demonstrated that intrinsic
      factors, such as secondary VKDB (e.g., EHBA, neonatal hepatitis, chronic
      diarrhea), should also be considered in infant autopsy cases presenting with
      subdural hemorrhage.

PMID- 22607981
TI  - Individual and environmental predictors of health risk behaviours among Dutch
      adolescents: the HBSC study.
AB  - OBJECTIVE: To examine unique and common predictors of tobacco smoking, binge
      drinking, cannabis smoking, early sexual intercourse and multiple health risk
      behaviours. STUDY DESIGN: Cross-sectional survey study. METHODS: The Dutch Health
      Behaviour in School-aged Children (HBSC) study was used to provide data on 1742
      adolescents aged 15 and 16 years of age. This study focused on a variety of
      individual and environmental predictors of health risk behaviours, tapping into
      four domains (mental health, family, peers and school), retrieved by adolescent
      self-reports and corrected for sociodemographic variables. Logistic and linear
      regression analyses were performed. RESULTS: Unique predictors (i.e., gender, low
      and very low education level, general health, hyperactivity problems, conduct
      problems, incomplete family, religion, knowledge of mother, parental rules on
      alcohol drinking, time spent with friends, number of friends, perceived tobacco
      use of classmates, truancy) were identified. In addition, common predictors
      (i.e., permissive rules on alcohol drinking and much time spent with friends)
      were also identified, explaining an increase in engagement in all investigated
      health risk behaviours in adolescence, including multiple risk behaviours.
      CONCLUSIONS: A prevention strategy targeting restrictive parenting and time spent
      with friends may be effective to reduce/discourage engagement in health risk
      behaviours.

PMID- 22607982
TI  - Intra-uterine growth restriction and increased risk of hypertension in adult
      life: a follow-up study of 50-year-olds.
AB  - OBJECTIVE: To compare blood pressure between 50-year-old adults who were born at
      term (37-42 weeks of gestation) with intra-uterine growth restriction (IUGR;
      birth weight <10th centile) and a control group of similar age born at term
      without IUGR (birth weight >=10th centile). STUDY DESIGN: Controlled comparative
      study. METHODS: Participants included 232 men and women who were born at the
      Royal Maternity Hospital, Belfast, a large regional maternity hospital in
      Northern Ireland, between 1954 and 1956. One hundred and eight subjects who were
      born with IUGR were compared with 124 controls with normal birth weight for
      gestation. The main outcome measures were systolic and diastolic blood pressure
      at approximately 50 years of age, measured according to European recommendations.
      RESULTS: The IUGR group had higher systolic and diastolic blood pressure than the
      control group: 131.5 [95% confidence interval (CI) 127.9-135.1] vs 127.1 (95% CI
      124.3-129.2) mmHg and 82.3 (95% CI 79.6-85.0) vs 79.0 (95% CI 77.0-81.0) mmHg,
      respectively. After adjustment for gender, the differences between the groups
      were statistically significant: systolic blood pressure 4.5 (95% CI 0.3-8.7) mmHg
      and diastolic blood pressure 3.4 (95% CI 0.2-6.5) mmHg (both P < 0.05). More
      participants in the IUGR group were receiving treatment for high blood pressure
      compared with the control group [16 (15%) vs 11 (9%)], although this was not
      statistically significant. The proportion of subjects with blood pressure >140/90
      mmHg or currently receiving antihypertensive treatment was 45% (n = 49) for the
      IUGR group, and 31% (n = 38) for the control group (odds ratio 1.9, 95% CI 1.1
      3.3). Adjustment for potential confounders made little difference. CONCLUSIONS:
      IUGR is associated with higher blood pressure at 50 years of age. Individuals
      born with IUGR should have regular blood pressure screening and early treatment
      as required. Hypertension remains underdiagnosed and undertreated in adult life.

PMID- 22607983
TI  - [Giant left ventricular pseudoaneurysm: the diagnostic contribution of different
      non-invasive imaging modalities].
AB  - Distinguishing between ventricular aneurysm and pseudoaneurysm, although
      difficult, is of major importance due to the therapeutic and prognostic
      implications. The present case highlights the pivotal role of non-invasive
      imaging modalities for differential diagnosis between these entities in order to
      ensure appropriate management of these patients.

PMID- 22607984
TI  - Respiratory muscle assessment in predicting extubation outcome in patients with
      stroke.
AB  - BACKGROUND: Patients with cerebral infarction often present impaired
      consciousness and unsatisfactory extubation. We aimed to assess the respiratory
      mechanics components that might be associated with the success of extubation in
      stroke patients. METHODS: Twenty consecutive patients with stroke who needed
      mechanical ventilation support were enrolled. The maximal inspiratory pressure,
      gastric and the esophageal pressure (Pdi/Pdimax), minute volume, respiratory
      rate, static compliance, airway resistance, rapid and superficial respiration
      index (RSRI), inspiratory time/total respiratory cycle (Ti/Ttot), and
      PaO(2)/FiO(2) were measured. RESULTS: The group who presented success to the
      extubation process presented 12.5+/-2.2=days in mechanical ventilation and the
      group who failed presented 13.1+/-2=days. The mean Ti/Ttot and Pdi/Pdimax for the
      failure group was 0.4+/-0.08 (0.36-0.44) and 0.5+/-0.7 (0.43-0.56), respectively.
      The Ti/Ttot ratio was 0.37+/-0.05 (0.34-0.41; p=0.0008) and the Pdi/Pdimax was
      0.25+/-0.05 for the success group (0.21-0.28; p<0.0001). A correlation was found
      between Pdi/Pdimax ratio and the RSRI (r=0.55; p=0.009) and PaO(2)/FiO(2) (r=
      0.59; p=0.005). Patients who presented a high RSRI (OR, 3.66; p=0.004) and Pdi
      (OR, 7.3; p=0.002), and low PaO(2)/FIO(2) (OR, 4.09; p=0.007), Pdi/Pdimax (OR,
      4.12; p=0.002) and RAW (OR, 3.0; p=0.02) developed mechanical ventilation
      extubation failure. CONCLUSION: Muscular fatigue index is an important predicting
      variable to the extubation process in prolonged mechanical ventilation of stroke
      patients.

PMID- 22607985
TI  - Pain perception in athletes compared to normally active controls: a systematic
      review with meta-analysis.
AB  - This study systematically reviewed differences in pain perception between
      athletes and normally active controls. We screened MEDLINE, Sport-Discus, EMBASE,
      Web of Science, PsycINFO, PSYNDEX, and the citations of original studies and
      systematic reviews. All studies on experimentally induced pain that compared pain
      perception between athletes and normally active controls were eligible. The main
      outcome measures were pain tolerance and pain threshold. Effects are described as
      standardized mean differences and were pooled using random-effects models.
      Fifteen studies including 899 subjects met the inclusion criteria. Twelve of
      these studies assessed pain tolerance, and 9 studies examined pain threshold. A
      meta-analysis of these studies revealed that athletes possessed higher pain
      tolerance compared to normally active controls (effect size calculated as Hedges'
      g=0.87, 95% confidence interval [CI(95)] 0.53-1.21; P<0.00001), whereas available
      data on pain threshold were less uniform (Hedges' g=0.69, CI(95) 0.16-1.21;
      P=0.01). After exclusion of studies with high risk of bias, differences between
      groups in pain threshold were not significant any longer. Our data suggest that
      regular physical activity is associated with specific alterations in pain
      perception. Psychological and biological factors that may be responsible for
      these alterations are discussed.

PMID- 22607986
TI  - Molecular diagnostics for congenital hearing loss including 15 deafness genes
      using a next generation sequencing platform.
AB  - BACKGROUND: Hereditary hearing loss (HL) can originate from mutations in one of
      many genes involved in the complex process of hearing. Identification of the
      genetic defects in patients is currently labor intensive and expensive. While
      screening with Sanger sequencing for GJB2 mutations is common, this is not the
      case for the other known deafness genes (> 60). Next generation sequencing
      technology (NGS) has the potential to be much more cost efficient. Published
      methods mainly use hybridization based target enrichment procedures that are time
      saving and efficient, but lead to loss in sensitivity. In this study we used a
      semi-automated PCR amplification and NGS in order to combine high sensitivity,
      speed and cost efficiency. RESULTS: In this proof of concept study, we screened
      15 autosomal recessive deafness genes in 5 patients with congenital genetic
      deafness. 646 specific primer pairs for all exons and most of the UTR of the 15
      selected genes were designed using primerXL. Using patient specific identifiers,
      all amplicons were pooled and analyzed using the Roche 454 NGS technology. Three
      of these patients are members of families in which a region of interest has
      previously been characterized by linkage studies. In these, we were able to
      identify two new mutations in CDH23 and OTOF. For another patient, the etiology
      of deafness was unclear, and no causal mutation was found. In a fifth patient,
      included as a positive control, we could confirm a known mutation in TMC1.
      CONCLUSIONS: We have developed an assay that holds great promise as a tool for
      screening patients with familial autosomal recessive nonsyndromal hearing loss
      (ARNSHL). For the first time, an efficient, reliable and cost effective genetic
      test, based on PCR enrichment, for newborns with undiagnosed deafness is
      available.

PMID- 22607987
TI  - [About two cases of intra-uterine incarceration post-vacuum aspiration: diagnosis
      and management].
AB  - We report two cases of endo-uterine incarceration occurred after vacuum
      aspiration. In the first case, it is a sigmoid fringe incarceration in a patient
      asymptomatic. In the second case, it is a fallopian incarceration whose diagnosis
      was made during an infertility evaluation. The hysterography, ultrasound and
      magnetic resonance imaging have confirmed these diagnoses. The treatment of these
      incarcerations was surgical and realized in two steps by hysteroscopy combined
      with laparoscopy. Monitoring by hysterography and hysteroscopy after three months
      has been proposed to assess the impact on future fertility.

PMID- 22607988
TI  - The prognostic significance of subsyndromal symptoms emerging after remission of
      late-life depression.
AB  - BACKGROUND: Attainment of remission is viewed as the optimal outcome of acute
      antidepressant treatment. However, some patients experience subsyndromal symptoms
      after they achieve remission. This study examines the prognostic significance of
      subsyndromal symptoms occurring during the first 6 months after remission of late
      life depression. METHOD: Older (age 60-89 years) in-patients and out-patients
      with unipolar major depression were followed until remission (asymptomatic or
      almost asymptomatic for 3 consecutive weeks). Two hundred and forty-two achieved
      remission after uncontrolled antidepressant treatment. This analysis focused on
      remitted patients who had follow-up data over a 2.5-year period (n = 185).
      RESULTS: Approximately 18% of patients relapsed. Of the remainder (n = 152),
      42.8% had subsyndromal depressive symptoms during the 6 months following
      remission. Cox's proportional survival analysis demonstrated that longer duration
      of subsyndromal symptoms [number of weeks with the Longitudinal Follow-up
      Examination (LIFE) Psychiatric Status Rating Scale (PSR) score of 3 or 4] in the
      first 6 months after remission was significantly associated with shorter time to
      recurrence and higher recurrence rate [hazard ratio (HR) 1.16, 95% confidence
      interval (CI) 1.08-1.24]. Based on our analysis, patients with 0, 4, 8 and 12
      weeks of subsyndromal symptoms in the first 6 months after remission have
      estimated recurrence rates of 28, 45, 66 and 86% respectively during the ensuing
      2 years. CONCLUSIONS: These findings highlight the clinical importance of
      subsyndromal symptoms occurring after remission in late-life depression. They
      also argue that studies of geriatric depression may complement the definition of
      remission with information on subsyndromal symptoms occurring after the initial
      asymptomatic period.

PMID- 22607989
TI  - Schmallenberg virus in calf born at term with porencephaly, Belgium.

PMID- 22607990
TI  - Mast cells and IgE activation do not alter the development of oral tolerance in a
      murine model.
AB  - BACKGROUND: In addition to their well-known role as potent effector cells in
      patients with allergic disease, mast cells have important immunomodulatory roles
      regulating tolerance in allograft rejection models. The roles of mast cells in
      oral tolerance development have not previously been examined. OBJECTIVE: We
      sought to evaluate the importance of mast cells, IgE-mediated mast cell
      activation, and histamine receptor 1 or 2 blockade on oral tolerance development
      in mice. METHODS: Oral tolerance was assessed in 2 mast cell-deficient murine
      strains (Kit(W-sh/W-sh) and Kit(W/W-v) mice) and control mice. Mice were fed
      ovalbumin (OVA) or peanut butter for 1 week and then immunized and boosted with
      relevant protein antigens. Antibody responses were assessed by using ELISA. The
      oral antihistamines pyrilamine and ranitidine were administered during tolerance
      induction to OVA. IgE-mediated mast cell activation was initiated during oral
      tolerance induction or OVA immunization. OVA-specific regulatory T cells were
      assessed in the Peyer patches, mesenteric lymph nodes, and spleens by using flow
      cytometry after adoptive transfer. RESULTS: Oral tolerance was successfully
      induced to OVA and peanut butter in mast cell-deficient mice. Kit(W-sh/W-sh) mice
      had higher proportions of antigen-specific regulatory T cells in the mesenteric
      lymph nodes than mast cell-containing control mice. However, mast cell
      reconstitution studies suggested this effect was mast cell independent. Oral
      antihistamine treatments with pyrilamine or ranitidine did not impair tolerance
      and neither did IgE-mediated activation. CONCLUSIONS: Mast cells are not
      necessary for the induction of oral tolerance, and allergic activation of mast
      cells does not impair tolerance to OVA. Oral antihistamine treatments do not
      disrupt the development of oral tolerance.

PMID- 22607991
TI  - The effect of parental allergy on childhood allergic diseases depends on the sex
      of the child.
AB  - BACKGROUND: The parent-of-origin effect is important in understanding the genetic
      basis of childhood allergic diseases and improving our ability to identify high
      risk children. OBJECTIVE: We sought to investigate the parent-of-origin effect in
      childhood allergic diseases. METHODS: The Isle of Wight Birth Cohort (n= 1456)
      has been examined at 1, 2, 4, 10, and 18 years of age. Information on the
      prevalence of asthma, eczema, rhinitis, and environmental factors was obtained by
      using validated questionnaires. Skin prick tests were carried out at ages 4, 10,
      and 18 years, and total IgE measurement was carried out at 10 and 18 years.
      Parental history of allergic disease was assessed soon after the birth of the
      child, when maternal IgE levels were also measured. Prevalence ratios (PRs) and
      their 95% CIs were estimated, applying log-linear models adjusted for confounding
      variables. RESULTS: When stratified for sex of the child, maternal asthma was
      associated with asthma in girls (PR, 1.91; 95% CI, 1.34-2.72; P= .0003) but not
      in boys (PR, 1.29; 95% CI, 0.85-1.96; P= .23), whereas paternal asthma was
      associated with asthma in boys (PR, 1.99; 95% CI, 1.42-2.79; P< .0001) but not in
      girls (PR, 1.03; 95% CI, 0.59-1.80; P= .92). Maternal eczema increased the risk
      of eczema in girls (PR, 1.92; 95% CI, 1.37-2.68; P= .0001) only, whereas paternal
      eczema did the same for boys (PR, 2.07; 95% CI, 1.32-3.25; P = .002). Similar
      trends were observed when the effect of maternal and paternal allergic disease
      was assessed for childhood atopy and when maternal total IgE levels were related
      to total IgE levels in children at ages 10 and 18 years. CONCLUSIONS: The current
      study indicates a sex-dependent association of parental allergic conditions with
      childhood allergies, with maternal allergy increasing the risk in girls and
      paternal allergy increasing the risk in boys. This has implications for childhood
      allergy prediction and prevention.

PMID- 22607993
TI  - Striking crosstalk of ROCK signaling with endothelial function.
AB  - Rho-associated coiled-coil forming protein kinases (ROCKs), the downstream target
      proteins of RhoA, are ubiquitously expressed serine-threonine protein kinases.
      ROCKs have diverse cellular functions, e.g. smooth muscle contraction, actin
      cytoskeleton organization, cell adhesion, and gene expression. Accumulating
      evidence has revealed that ROCKs are substantially involved in cardiovascular
      disorders such as angina, cerebral ischemia, myocardial ischemia, and cardiac
      hypertrophy. So far, the significant relationship of ROCKs with endothelial
      function has been reported. ROCKs inhibition by statins or other selective
      inhibitors leads to the upregulation and activation of endothelial nitric oxide
      synthase, resulting in the reduction of vascular inflammation and
      atherosclerosis. Meanwhile, it has been also demonstrated that endogenous nitric
      oxide could inhibit RhoA/ROCK signaling pathway. Taken together, there might be
      critical crosstalk of ROCKs with endothelial function. In addition, we further
      focus on leukocyte ROCK activity as a surrogate marker in patients with
      atherosclerosis-related diseases. Indeed, leukocyte ROCK activity has been shown
      to be increased in atherosclerotic patients, indicating the possible usage of
      leukocyte ROCK activity as a surrogate marker similar to endothelial function
      evaluated by flow-mediated dilation. Here, we review concerning ROCK signaling
      pathway, especially focusing on the crosstalk of ROCKs with endothelial function.

PMID- 22607992
TI  - Genome-wide ancestry association testing identifies a common European variant on
      6q14.1 as a risk factor for asthma in African American subjects.
AB  - BACKGROUND: Genetic variants that contribute to asthma susceptibility might be
      present at varying frequencies in different populations, which is an important
      consideration and advantage for performing genetic association studies in admixed
      populations. OBJECTIVE: We sought to identify asthma-associated loci in African
      American subjects. METHODS: We compared local African and European ancestry
      estimated from dense single nucleotide polymorphism genotype data in African
      American adults with asthma and nonasthmatic control subjects. Allelic tests of
      association were performed within the candidate regions identified, correcting
      for local European admixture. RESULTS: We identified a significant ancestry
      association peak on chromosome 6q. Allelic tests for association within this
      region identified a single nucleotide polymorphism (rs1361549) on 6q14.1 that was
      associated with asthma exclusively in African American subjects with local
      European admixture (odds ratio, 2.2). The risk allele is common in Europe (42% in
      the HapMap population of Utah residents with Northern and Western European
      ancestry from the Centre d'Etude du Polymorphisme Humain collection) but absent
      in West Africa (0% in the HapMap population of Yorubans in Ibadan, Nigeria),
      suggesting the allele is present in African American subjects because of recent
      European admixture. We replicated our findings in Puerto Rican subjects and
      similarly found that the signal of association is largely specific to subjects
      who are heterozygous for African and non-African ancestry at 6q14.1. However, we
      found no evidence for association in European American or Puerto Rican subjects
      in the absence of local African ancestry, suggesting that the association with
      asthma at rs1361549 is due to an environmental or genetic interaction.
      CONCLUSION: We identified a novel asthma-associated locus that is relevant to
      admixed populations with African ancestry and highlight the importance of
      considering local ancestry in genetic association studies of admixed populations.

PMID- 22607994
TI  - Development of the primary measurement standard for gaseous radon-222 activity.
AB  - The Korea Research Institute of Standards and Science (KRISS) has developed a
      primary system for the activity standardization of gaseous radon-222, based on
      the defined solid angle counting method. The size of adsorbed radon is determined
      by a Cyclone Storage Phosphor System, and a buffer chamber is introduced between
      the measurement chamber and the source for the purpose of gas purification. The
      measured activity of gaseous radon-222 and its associated measurement uncertainty
      obtained using the system are presented.

PMID- 22607995
TI  - The practicality of including the systemic inflammatory response syndrome in the
      definition of polytrauma: experience of a level one trauma centre.
AB  - BACKGROUND: The systemic inflammatory response syndrome (SIRS) has been advocated
      as a significant predictor of outcome in trauma. Recent trauma literature has
      proposed SIRS as a surrogate for physiological derangements characteristic of
      polytrauma with some authors recommending its inclusion into the definition of
      polytrauma. The practicality of daily SIRS collection outside of specifically
      designed prospective trials is unknown. The purpose of this study was to assess
      the availability of SIRS variables and its appropriateness for inclusion into a
      definition of polytrauma. We hypothesised SIRS variables would be readily
      available and easy to collect, thus represent an appropriate inclusion into the
      definition of polytrauma. METHOD: A prospective observational study of all trauma
      team activation patients over 7-months (August 2009 to February 2010) at a
      University affiliated level-1 urban trauma centre. SIRS data (temperature>38
      degrees C or <36 degrees C; Pulse >90 bpm; RR>20/min or a PaCO(2)<32 mmHg;
      WCC>12.0*10(9)L(-1), or <4.0*10(9)L(-1), or the presence of >10 immature bands)
      collected from presentation, at 24 h intervals until 72 h post injury. Inclusion
      criteria were all patients generating a trauma team activation response age >16.
      RESULTS: 336 patients met inclusion criteria. In 46% (155/336) serial SIRS scores
      could not be calculated due to missing data. Lowest rates of missing data
      observed on admission [3% (11/336)]. Stratified by ISS>15 (132/336), in 7%
      (9/132) serial SIRS scores could not be calculated due to missing data. In 123
      patients ISS>15 with complete data, 81% (100/123) developed SIRS. For Abbreviated
      Injury Scale (AIS)>2 in at least 2 body regions (64/336) in 5% (3/64) serial SIRS
      scores could not be calculated, with 92% (56/61) of patients with complete data
      developing SIRS. For Direct ICU admissions [25% (85/336)] 5% (4/85) of patients
      could not have serial SIRS calculated [mean ISS 15(+/-11)] and 90% (73/81)
      developed SIRS at least once over 72 h. CONCLUSION: Based on the experience of
      our level-1 trauma centre, the practicability of including SIRS into the
      definition of polytrauma as a surrogate for physiological derangement appears
      questionable even in prospective fashion.

PMID- 22607996
TI  - The management of bite wounds in children--a retrospective analysis at a level I
      trauma centre.
AB  - INTRODUCTION: Animal bite wounds are a significant problem, which have caused
      several preventable child deaths in clinical practice in the past. The majority
      of bite wounds is caused by dogs and cats, and also humans have to be considered
      to lead to those extreme complicated diagnosis in the paediatric patient
      population. Early estimation of infection risk, adequate antibiotic therapy and,
      if indicated, surgical treatment, are cornerstones of successful cures of bite
      wounds. However, antibiotic prophylaxis and wound management are discussed
      controversially in the current literature. In our study, we retrospectively
      investigated the bite source, infection risk and treatment options of paediatric
      bite wounds. METHODS: A total of 1592 paediatric trauma patients were analysed
      over a period of 19 years in this retrospective study at a level I trauma centre,
      Department of Trauma Surgery, Medical University of Vienna, Austria. Data for
      this study were obtained from our electronic patient records and follow-up
      visits. In our database, all paediatric patients triaged to our major urban
      trauma centre have been entered retrospectively. RESULTS: During the 19-year
      study period, 1592 paediatric trauma patients met the inclusion criteria. The
      mean age was 7.7 years (range 0-18.9), 878 (55.2%) were males and 714 (44.8%)
      were females. In our study population, a total of 698 dog bites (43.8%), 694
      human bites (43.6%), 138 other bites (8.7%) and 62 cat bites (3.9%) have been
      observed. A total of 171 wounds (10.7%) have been infected. Surgical intervention
      was done in 27 wounds (1.7%). CONCLUSION: Gender-related incidence in bite wounds
      for dog and cat could be detected. Second, our findings for originator of bite
      wounds reflect the findings in the published literature. Total infection rate
      reached 10.7%, primary antibiotic therapy was administered in 221 cases (13.9%)
      and secondary antibiotic therapy in 20 (1.3%) cases. Observed infection rate of
      punctured wounds and wounds greater than 3 cm was 3 times higher than for all
      other wounds. Our findings need to be proven in further prospective clinical
      trials.

PMID- 22607997
TI  - Optimising management of the elderly trauma patient.

PMID- 22607998
TI  - Detection of small fenestral otosclerotic lesions by high-resolution computed
      tomography using multiplanar reconstruction.
AB  - OBJECTIVE: The aim of this study was to assess the value of multislice computed
      tomography (MSCT) using multiplanar reconstruction (MPR) to detect the small
      fenestral lesions in patients with otosclerosis. METHODS: MSCT with MPR imaging
      was used to evaluate 27 ears of 17 patients with otosclerosis (3 male and 14
      females) ranging in age from 33 to 69 years with a mean of 49.8 year. MSCT
      imaging was performed using Aquilion(r). Axial spiral scans with a 0.5-mm slice
      thickness were obtained. The acquired high-resolution data were transferred to a
      workstation (ALATO VIEW). MPR images were created in the planes parallel to the
      stapedial crus and then analyzed on the monitor screen by two radiologists (Y.T.
      and N.K.). RESULTS: MPR images showed abnormal findings in 26 of 27 ears with
      otosclerosis (96%), whereas axial images showed abnormal findings in only 15 of
      27 ears (56%). The similar classification between both images was shown only in 9
      of 27 ears (33%). In 16 ears (67%) axial images under-evaluated the lesions
      compared with MPR images. MPR images detected smaller foci than axial images. Air
      bone gap at 0.5-4kHz tended to increase dependently on the extension of fenestral
      lesions evaluated by MPR images. CONCLUSION: MPR images detected fenestral
      lesions in otosclerosis more frequently and more precisely than axial images. The
      extent of fenestral lesions observed on MPR images tends to be related to the
      degree of conductive hearing loss.

PMID- 22607999
TI  - Community survey after rabies outbreaks, Flagstaff, Arizona, USA.
AB  - Flagstaff, Arizona, USA, experienced notable outbreaks of rabies caused by a bat
      rabies virus variant in carnivore species in 2001, 2004, 2005, 2008, and 2009.
      The most recent epizootic involved transmission among skunk and fox populations
      and human exposures. Multiple, wide-ranging control efforts and health
      communications outreach were instituted in 2009, including a household survey
      given to community members. Although the Flagstaff community is knowledgeable
      about rabies and the ongoing outbreaks in general, gaps in knowledge about routes
      of exposure and potential hosts remain. Future educational efforts should include
      messages on the dangers of animal translocation and a focus on veterinarians and
      physicians as valuable sources for outreach. These results will be useful to
      communities experiencing rabies outbreaks as well as those at current risk.

PMID- 22608000
TI  - Analysis of the morphology and distribution of argentaffin, argyrophil and
      insulin-immunoreactive endocrine cells in the small intestine of the adult
      opossum Didelphis aurita (Wied-Neuwied, 1826).
AB  - The aim of this study was to identify and quantify the argyrophil, argentaffin
      and insulin-immunoreactive cells (IIC) in the small intestine of the opossum
      Didelphis aurita. Seven adult male specimens of opossums were investigated. The
      animals were captured, and their blood insulin levels were determined. After
      euthanasia, fragments of the small intestine were processed for light microscopy
      and transmission electron microscopy, and submitted to histochemistry and
      immunohistochemistry for identification of argyrophil and argentaffin endocrine
      cells, and IIC. Argyrophil and argentaffin cells were identified in the
      intestinal villi and Liberkuhn crypts, whereas IIC were present exclusively in
      the crypts. Ultrastructure of the IIC revealed cytoplasmic granules of different
      sizes and electron densities. The numbers of IIC per mm(2) in the duodenum and
      jejunum were higher than in the ileum (p<0.05). The animals had low levels of
      blood insulin (2.8 +/- 0.78 MUIU/ml). There was no correlation between insulin
      levels and the number of IIC in the small intestine. The IIC presented secretory
      granules, elongated and variable morphology. It is believed that insulin
      secretion by the IIC may influence the proliferation of cells in the Liberkuhn
      crypts, and local glucose homeostasis, primarily in animals with low serum
      insulin levels, such as the opossum.

PMID- 22608001
TI  - Idiopathic avascular necrosis of the scaphoid: 10 new cases and a review of the
      literature. Indications for Preiser's disease.
AB  - INTRODUCTION: Avascular necrosis of the scaphoid (Preiser's disease) is a rare
      entity for which there are no treatment guidelines to date. The aim of this study
      was to delineate the optimal treatment at different stages of this disease, based
      on an analysis of the cases treated in our department. MATERIALS AND METHODS: Ten
      wrists (nine patients) were retrospectively reviewed after a mean 92 months of
      follow-up. The initial diagnosis was stage II avascular necrosis in four cases,
      stage III in four cases and stage IV in two cases. These patients were treated by
      conservative treatment (non surgical) in three cases, vascularized bone graft in
      two and palliative treatments (proximal row carpectomy or partial fusion) in
      five. Radiological examination, sometimes completed by MRI, and functional
      assessment of range of motion, grip strength and Mayo Wrist Score were performed.
      RESULTS: Completely different results were obtained in the two stage II cases
      treated by conservative treatment, while functional results improved in the two
      cases treated by vascularized bone graft with regression of necrosis on MRI. Pain
      improved following palliative treatment in 4/5 stage III and IV wrists.
      Functional results were satisfactory with conservative treatment in one stage IV
      case for 13 years but worsened at the final follow-up assessment. DISCUSSION: A
      review of the literature, including 126 cases in 29 articles clarified the role
      of conservative treatment, vascularized bone grafts and proximal row carpectomy
      in the treatment of avascular necrosis of the scaphoid. Conservative treatment is
      ineffective in the early stages and nearly always results in disease progression.
      In contrast vascularized bone grafts can stop or even reverse damage at stage II.
      Palliative treatment is indicated when facing irreversible lesions. LEVEL OF
      EVIDENCE: Level IV - Retrospective study.

PMID- 22608002
TI  - RCDB: Renal Cancer Gene Database.
AB  - BACKGROUND: Renal cell carcinoma or RCC is one of the common and most lethal
      urological cancers, with 40% of the patients succumbing to death because of
      metastatic progression of the disease. Treatment of metastatic RCC remains highly
      challenging because of its resistance to chemotherapy as well as radiotherapy,
      besides surgical resection. Whereas RCC comprises tumors with differing
      histological types, clear cell RCC remains the most common. A major problem in
      the clinical management of patients presenting with localized ccRCC is the
      inability to determine tumor aggressiveness and accurately predict the risk of
      metastasis following surgery. As a measure to improve the diagnosis and prognosis
      of RCC, researchers have identified several molecular markers through a number of
      techniques. However the wealth of information available is scattered in
      literature and not easily amenable to data-mining. To reduce this gap, this work
      describes a comprehensive repository called Renal Cancer Gene Database, as an
      integrated gateway to study renal cancer related data. FINDINGS: Renal Cancer
      Gene Database is a manually curated compendium of 240 protein-coding and 269
      miRNA genes contributing to the etiology and pathogenesis of various forms of
      renal cell carcinomas. The protein coding genes have been classified according to
      the kind of gene alteration observed in RCC. RCDB also includes the
      miRNAsdysregulated in RCC, along with the corresponding information regarding the
      type of RCC and/or metastatic or prognostic significance. While some of the miRNA
      genes showed an association with other types of cancers few were unique to RCC.
      Users can query the database using keywords, category and chromosomal location of
      the genes. The knowledgebase can be freely accessed via a user-friendly web
      interface at http://www.juit.ac.in/attachments/jsr/rcdb/homenew.html.
      CONCLUSIONS: It is hoped that this database would serve as a useful complement to
      the existing public resources and as a good starting point for researchers and
      physicians interested in RCC genetics.

PMID- 22608003
TI  - [WHO grade II gliomas: review of the current management].
AB  - The optimal management of diffuse WHO grade II gliomas (GGII) is still
      controversial. Some authors propose a long-term radiological follow-up of the
      tumor, others perform a biopsy and treat only if clinical or radiological signs
      of progression, finally, others propose an active treatment from diagnosis. There
      is mounting evidence that suggest that expectant management is no longer optimal,
      supporting active treatment from diagnosis. In the present work, an extensive
      review of the recent literature was performed, in order to clarify some of these
      controversies. Neuroimaging techniques, such as magnetic resonance imaging (MRI),
      multivoxel spectroscopy or methionine positron emission tomography (PET), give
      valuable information about the tumor, but lack of sufficient reliability to make
      a definitive diagnosis of GGII. Stereotactic biopsy leads to misdiagnosis in up
      to 71% of cases, which has been associated with sampling errors and inter
      observer variability due to the small sample obtained. Therefore, it is now
      considered that a definitive diagnosis of GGII requires a detailed histological
      analysis of the sample after maximum tumor removal. Despite the lack of class I
      evidence, there is growing evidence from cohort studies, favoring extensive
      surgical resection to improve survival and time to tumor degeneration. Surgery is
      also effective to treat epilepsy, as an improvement in up to 76% of drug
      resistant epilepsies has been documented. Consequently, surgery is now considered
      as a crucial step for diagnosis and treatment of these tumors. Early radiotherapy
      after surgery lengthens the period without progression but does not affect
      overall survival, and is related to cognitive disorders that affect quality of
      life. Hence, this treatment could be deferred until tumor progression.

PMID- 22608004
TI  - Combined toxicity of cadmium and lead on the earthworm Eisenia fetida (Annelida,
      Oligochaeta).
AB  - Cadmium (Cd) and lead (Pb) in soil have received extensive attention due to their
      potential toxicological effects. This study analyzed the combined toxicity of Cd
      and Pb on the earthworm Eisenia fetida. Cellulase activity and DNA damage were
      chosen as toxic endpoints. Factorial analysis was applied to identify the
      interaction of Cd and Pb. The results showed that single Pb and Cd could increase
      the cellulase activity and DNA damage of coelomocytes. The combination of both
      metals could significantly inhibit cellulase activity. For low Cd concentration,
      the addition of Pb could increase the DNA damage. However, for high Cd
      concentration, Pb could decrease the DNA damage. Factorial analysis showed that
      the changes of Cd concentrations exerted the highest influence on the combined
      toxicity, followed by factor "Cd*Pb" and "Pb". The combined toxicological effects
      between Cd and Pb were complex, which might be influenced by the competition
      adsorption of both metals in soil and biomembrane and their bioavailability. The
      results of this study are useful for understanding of combined toxicity of Cd and
      Pb on terrestrial invertebrates.

PMID- 22608005
TI  - Mucociliary clearance and its relation with the level of physical activity in
      daily life in healthy smokers and nonsmokers.
AB  - OBJECTIVES: To investigate the relationship between mucociliary transport and
      physical activity in daily life (PADL) in smokers and nonsmokers. METHODS: Fifty
      two current smokers were submitted to assessment of mucociliary transport
      (Sacharin Transit Time, STT), carbon monoxide levels in the exhaled air, lung
      function and smoking history. In addition, subjects kept a pedometer worn at the
      waist for six days in order to determine their level of PADL (steps/day). The
      tests were also performed on 30 matched healthy nonsmokers who served as control
      group. RESULTS: Light smokers (<=15 cigarettes/day) had a STT of 9 (7-11) min
      (median [confidence interval]), which was similar to nonsmokers (8 [8-11]min;
      p=0.8). Both moderate (16-25 cigarettes/day) and heavy (>25 cigarettes/day)
      smokers had significantly higher STT (13 [11-17] min and 13 [10-21] min,
      respectively) than nonsmokers and light smokers (p<0.05 for all). There was no
      difference in the number of steps/day between any of the groups (p>0.05 for all).
      In the general group of smokers, STT was not significantly correlated with PADL,
      pack/years index, years of smoking or age (r<-0.23; p>0.09 for all). There was
      significant negative correlation between STT and PADL only in light smokers (r=
      0.55; p=0.02) and nonsmokers (r=-0.42; p=0.02), but not in moderate and heavy
      smokers. CONCLUSION: In light smokers and non-smokers, better mucociliary
      function is associated to higher daily physical activity level, as opposed to the
      decreased mucociliary function observed in smokers, i.e., those with moderate and
      heavy cigarette consumption.

PMID- 22608006
TI  - Clinical significance of ERCC2 haplotype-tagging single nucleotide polymorphisms
      in patients with unresectable non-small cell lung cancer treated with first-line
      platinum-based chemotherapy.
AB  - BACKGROUND: First-line platinum-based chemotherapy is currently considered the
      standard treatment for unresectable non-small cell lung cancer (NSCLC). However,
      resistance to platinum-based chemotherapy results in poor prognoses. The DNA
      repair pathway is a crucial molecular mechanism potentially involved in
      resistance to platinum-based chemotherapy. ERCC2 plays an integral role in the
      nucleotide excision repair pathway. Furthermore, single nucleotide polymorphisms
      (SNPs) and haplotypes in the ERCC2 gene are thought to be associated with the
      risk of developing lung cancer and clinical outcomes. Therefore, we evaluated the
      impact of ERCC2 haplotype-tagging SNPs (htSNPs) on the clinical parameters of
      first-line platinum-based chemotherapy in unresectable NSCLC. PATIENTS AND
      METHODS: We genotyped 8 ERCC2 htSNPs for 129 unresectable NSCLC (stage IIIA, 12;
      stage III, 36; stage IV, 82) cases treated with first-line platinum-based
      chemotherapy. Clinical characteristics, treatment outcomes, hematological and non
      hematological toxicities, and predictive value of the htSNPs in patient response,
      survival, and adverse events related to platinum-based chemotherapy were analyzed
      according to each ERCC2 htSNP using the chi-square test, Kaplan-Meier method, and
      Cox proportional hazard model. RESULTS: No differences were observed in patient
      or disease characteristics and response according to ERCC2 htSNPs. In a survival
      analysis, rs50872 was significantly related to overall survival (OS) (log-rank
      test, p=0.014). The median survival duration of rs50872 G/G, A/G, and A/A
      genotypes was 35.75 (95% confidence interval [CI] 21.05-50.45), 36.07 (hazard
      ratio [HR] 1.02, 95% CI 25.20-46.94), and 16.75 (HR 3.49, 95% CI 5.73-27.77)
      months, respectively. A significant association was observed between grades 3 and
      4 infections and poor survival: OS in patients with a grade 0-2 infection: 35.75
      months (95% CI 28.15-43.35); OS in patients with a grade 3-4 infection: 12.86
      months (95% CI 8.99-16.72, HR 3.57) (log-rank test, p<0.001). In a subgroup
      analysis based on taxane-platinum vs. gemcitabine-platinum doublets, the rs238405
      genotype was significantly related to OS in the taxane-platinum doublets group.
      However, the rs238416 genotype was significantly associated with OS in the
      gemcitabine-based group. CONCLUSIONS: ERCC2 htSNPs rs50872 (overall), rs238405
      (taxane-platinum doublets group), and rs238416 (gemcitabine-platinum doublets
      group) and infection related to first-line chemotherapy were associated with OS
      in unresectable NSCLC patients treated with first-line platinum-based
      chemotherapy. However, additional large prospective studies focusing on the role
      of ERCC2 htSNPs in unresectable NSCLC are needed.

PMID- 22608007
TI  - Adenosine signaling promotes regeneration of pancreatic beta cells in vivo.
AB  - Diabetes can be controlled with insulin injections, but a curative approach that
      restores the number of insulin-producing beta cells is still needed. Using a
      zebrafish model of diabetes, we screened ~7,000 small molecules to identify
      enhancers of beta cell regeneration. The compounds we identified converge on the
      adenosine signaling pathway and include exogenous agonists and compounds that
      inhibit degradation of endogenously produced adenosine. The most potent enhancer
      of beta cell regeneration was the adenosine agonist 5'-N
      ethylcarboxamidoadenosine (NECA), which, acting through the adenosine receptor
      A2aa, increased beta cell proliferation and accelerated restoration of
      normoglycemia in zebrafish. Despite markedly stimulating beta cell proliferation
      during regeneration, NECA had only a modest effect during development. The
      proliferative and glucose-lowering effect of NECA was confirmed in diabetic mice,
      suggesting an evolutionarily conserved role for adenosine in beta cell
      regeneration. With this whole-organism screen, we identified components of the
      adenosine pathway that could be therapeutically targeted for the treatment of
      diabetes.

PMID- 22608008
TI  - Time-restricted feeding without reducing caloric intake prevents metabolic
      diseases in mice fed a high-fat diet.
AB  - While diet-induced obesity has been exclusively attributed to increased caloric
      intake from fat, animals fed a high-fat diet (HFD) ad libitum (ad lib) eat
      frequently throughout day and night, disrupting the normal feeding cycle. To test
      whether obesity and metabolic diseases result from HFD or disruption of metabolic
      cycles, we subjected mice to either ad lib or time-restricted feeding (tRF) of a
      HFD for 8 hr per day. Mice under tRF consume equivalent calories from HFD as
      those with ad lib access yet are protected against obesity, hyperinsulinemia,
      hepatic steatosis, and inflammation and have improved motor coordination. The tRF
      regimen improved CREB, mTOR, and AMPK pathway function and oscillations of the
      circadian clock and their target genes' expression. These changes in catabolic
      and anabolic pathways altered liver metabolome and improved nutrient utilization
      and energy expenditure. We demonstrate in mice that tRF regimen is a
      nonpharmacological strategy against obesity and associated diseases.

PMID- 22608009
TI  - Drinking hydrogen water and intermittent hydrogen gas exposure, but not lactulose
      or continuous hydrogen gas exposure, prevent 6-hydorxydopamine-induced
      Parkinson's disease in rats.
AB  - BACKGROUND: Lactulose is a synthetic disaccharide that can be catalyzed only by
      intestinal bacteria in humans and rodents, and a large amount of hydrogen is
      produced by bacterial catalysis of lactulose. We previously reported marked
      effects of ad libitum administration of hydrogen water on prevention of a rat
      model of Parkinson's disease (PD). METHODS: End-alveolar breath hydrogen
      concentrations were measured in 28 healthy subjects and 37 PD patients, as well
      as in 9 rats after taking hydrogen water or lactulose. Six-hydroxydopamine (6
      OHDA)-induced hemi-PD model was stereotactically generated in rats. We compared
      effects of hydrogen water and lactulose on prevention of PD. We also analyzed
      effects of continuous and intermittent administration of 2% hydrogen gas.
      RESULTS: Hydrogen water increased breath hydrogen concentrations from 8.6 +/- 2.1
      to 32.6 +/- 3.3 ppm (mean and SEM, n = 8) in 10 min in healthy subjects.
      Lactulose increased breath hydrogen concentrations in 86% of healthy subjects and
      59% of PD patients. Compared to monophasic hydrogen increases in 71% of healthy
      subjects, 32% and 41% of PD patients showed biphasic and no increases,
      respectively. Lactulose also increased breath hydrogen levels monophasically in 9
      rats. Lactulose, however, marginally ameliorated 6-OHDA-induced PD in rats.
      Continuous administration of 2% hydrogen gas similarly had marginal effects. On
      the other hand, intermittent administration of 2% hydrogen gas prevented PD in 4
      of 6 rats. CONCLUSIONS: Lack of dose responses of hydrogen and the presence of
      favorable effects with hydrogen water and intermittent hydrogen gas suggest that
      signal modulating activities of hydrogen are likely to be instrumental in
      exerting a protective effect against PD.

PMID- 22608011
TI  - Six-month outcome of elderly people hospitalized via the emergency department:
      the SAFES cohort.
AB  - BACKGROUND: The objective of the study was to identify factors predictive of 6
      month institutionalization or mortality in frail elderly patients after acute
      hospitalization. METHODS: A prospective cohort of elderly subjects 75 years and
      older was set up in nine French teaching hospitals. Data obtained from a
      comprehensive geriatric assessment were used in a Cox model to predict 6-month
      institutionalization or mortality. Institutionalization was defined as incident
      admission either to a nursing home or other long-term care facility during the
      follow-up period. RESULTS: Crude institutionalization and death rates after 6
      months of follow-up were 18% and 24%, respectively. Independent predictors of
      institutionalization were: living alone (HR=1.83; 95% CI=1.27-2.62) or a higher
      number of children (HR=0.86; 95% CI=0.78-0.96), balance problems (HR=1.72; 95%
      CI=1.19-2.47), malnutrition or risk thereof (HR=1.93; 95% CI=1.24-3.01), and
      dementia syndrome (HR=1.88; 95% CI=1.32-2.67). Factors found to be independently
      related to 6-month mortality were exclusively medical factors: malnutrition or
      risk thereof (HR=1.92; 95% CI=1.17-3.16), delirium (HR=1.80; 95% CI=1.24-2.62),
      and a high level of comorbidity (HR=1.62; 95% CI=1.09-2.40). Institutionalization
      (HR=1.92; 95% CI=1.37-2.71) and unplanned readmission (HR=4.47; 95% CI=3.16-2.71)
      within the follow-up period were also found as independent predictors.
      CONCLUSION: The main factors predictive of 6-month outcome identified in this
      study are modifiable by global and multidisciplinary interventions. Their early
      identification and management would make it possible to modify frail elderly
      subjects' prognosis favorably.

PMID- 22608010
TI  - Neurobehavioral disinhibition predicts initiation of substance use in children
      with prenatal cocaine exposure.
AB  - BACKGROUND: In previous work we (Fisher et al., 2011) examined the emergence of
      neurobehavioral disinhibition (ND) in adolescents with prenatal substance
      exposure. We computed ND factor scores at three age points (8/9, 11 and 13/14
      years) and found that both prenatal substance exposure and early adversity
      predicted ND. The purpose of the current study was to determine the association
      between these ND scores and initiation of substance use between ages 8 and 16 in
      this cohort as early initiation of substance use has been related to later
      substance use disorders. Our hypothesis was that prenatal cocaine exposure
      predisposes the child to ND, which, in turn, is associated with initiation of
      substance use by age 16. METHODS: We studied 386 cocaine exposed and 517
      unexposed children followed since birth in a longitudinal study. Five dichotomous
      variables were computed based on the subject's report of substance use: alcohol
      only; tobacco only; marijuana only; illicit substances and any substance.
      RESULTS: Cox proportional hazard regression showed that the 8/9 year ND score was
      related to initiation of alcohol, tobacco, illicit and any substance use but not
      marijuana use. The trajectory of ND across the three age periods was related to
      substance use initiation in all five substance use categories. Prenatal cocaine
      exposure, although initially related to tobacco, marijuana and illicit substance
      initiation, was no longer significant with ND scores in the models. CONCLUSION:
      Prenatal drug exposure appears to be a risk pathway to ND, which by 8/9 years
      portends substance use initiation.

PMID- 22608012
TI  - Imprisonment, alcohol dependence and risk of delusional disorder: a cross
      sectional study.
AB  - BACKGROUND: Compared to the general population, an excess of psychotic illnesses,
      major depression and dependence disorders among prisoners has been reported.
      However, the impact of prison on detainees' psychopathology has rarely been
      studied. OBJECTIVE: To determine the mental disorders liable to develop or
      regress on entry into prison and over time. METHOD: Two samples of French
      prisoners detained in local prisons were interviewed using the same methodology.
      The first sample consisted of 267 new arrivals. The second was a random sample of
      450 prisoners. Diagnoses were assessed using a thorough methodology: each
      prisoner was interviewed for approximately 2 hours by two clinicians. One of the
      clinicians used a structured clinical interview, which generates DSM IV diagnoses
      (MINI plus v 5.0); the second completed the procedure with an open clinical
      interview. The final DSM IV diagnoses were obtained as a consensus between the
      two approaches. Multilevel logistic regressions were used to take into account
      potential confounders. RESULTS: Prevalence rates of mental disorders were
      substantially higher in prison even for the sample of newcomers (major depression
      disorder: 24.7%, substance dependence: 17.6% and schizophrenia: 4.1%). Alcohol
      dependence disorder was significantly more frequent in the sample of newcomers
      (OR 1.84 [1.01-3.51]). No significant difference was evidenced between samples
      for substance dependence disorder. Psychotic disorders were significantly less
      frequent at entry into prison, particularly delusional disorder (OR 0.29 [0.08
      0.98]). CONCLUSION: This study shows the contrasted potential effects of prison
      on psychopathology: alcohol dependence disorders were significantly more frequent
      for the newcomers, while the frequency of delusional disorders was lower. This
      evidence is arguing in favour of the validity of the old concept: prison
      psychosis. Moreover, prisoners should receive relevant help from clinicians to
      cope with these disorders.

PMID- 22608013
TI  - Zoonotic disease pathogens in fish used for pedicure.

PMID- 22608014
TI  - High versus low level of response to alcohol: evidence of differential reactivity
      to emotional stimuli.
AB  - BACKGROUND: The low level of response (LR) or sensitivity to alcohol is
      genetically influenced and predicts heavy drinking and alcohol problems.
      Functional magnetic resonance imaging (fMRI) studies using cognitive tasks
      suggest that subjects with a low-LR process cognitive information differently
      after placebo and alcohol than those with a high LR, but no studies have
      evaluated whether similar LR group differences are seen during an emotional
      processing task. METHODS: The fMRI data were gathered from 116 nonalcoholic
      subjects (60 women) after oral placebo or approximately .7 mL/kg of ethanol while
      performing a modified emotional faces processing task. These included 58 low- and
      high-LR pairs matched on demography and aspects of substance use. RESULTS: Blood
      alcohol levels and task performance were similar across LR groups, but low-LR
      subjects consumed approximately .8 drinks more/occasion. Thirteen brain regions
      (mostly the middle and inferior frontal gyri, cingulate, and insula) showed
      significant LR group or LR * placebo/alcohol condition interactions for emotional
      (mostly happy) faces relative to non-face trials. Low-LR subjects generally
      showed decreasing blood-oxygen level-dependent response contrasts across placebo
      to alcohol, whereas high LR showed increasing contrasts from placebo to alcohol,
      even after controlling for drinking quantities and alcohol-related changes in
      cerebral blood flow. CONCLUSIONS: Thus, LR group fMRI differences are as
      prominent during an emotional face task as during cognitive paradigms. Low-LR
      individuals processed both types of information in a manner that might contribute
      to an impaired ability to recognize modest levels of alcohol intoxication in a
      range of life situations.

PMID- 22608015
TI  - Adverse childhood experiences in relation to mood and anxiety disorders in a
      population-based sample of active military personnel.
AB  - BACKGROUND: Although it has been posited that exposure to adverse childhood
      experiences (ACEs) increases vulnerability to deployment stress, previous
      literature in this area has demonstrated conflicting results. Using a cross
      sectional population-based sample of active military personnel, the present study
      examined the relationship between ACEs, deployment related stressors and mood and
      anxiety disorders. METHOD: Data were analyzed from the 2002 Canadian Community
      Health Survey-Canadian Forces Supplement (CCHS-CFS; n = 8340, age 18-54 years,
      response rate 81%). The following ACEs were self-reported retrospectively:
      childhood physical abuse, childhood sexual abuse, economic deprivation, exposure
      to domestic violence, parental divorce/separation, parental substance abuse
      problems, hospitalization as a child, and apprehension by a child protection
      service. DSM-IV mood and anxiety disorders [major depressive disorder, post
      traumatic stress disorder (PTSD), generalized anxiety disorder (GAD), panic
      attacks/disorder and social phobia] were assessed using the composite
      international diagnostic interview (CIDI). RESULTS: Even after adjusting for the
      effects of deployment-related traumatic exposures (DRTEs), exposure to ACEs was
      significantly associated with past-year mood or anxiety disorder among men
      [adjusted odds ratio (aOR) 1.34, 99% confidence interval (CI) 1.03-1.73, p <
      0.01] and women [aOR 1.37, 99% CI 1.00-1.89, p = 0.01]. Participants exposed to
      both ACEs and DRTEs had the highest prevalence of past-year mood or anxiety
      disorder in comparison to those who were exposed to either ACEs alone, DRTEs
      alone, or no exposure. CONCLUSIONS: ACEs are associated with several mood and
      anxiety disorders among active military personnel. Intervention strategies to
      prevent mental health problems should consider the utility of targeting soldiers
      with exposure to ACEs.

PMID- 22608016
TI  - Olmesartan for the prevention or delay of diabetic nephropathy: some
      considerations.

PMID- 22608017
TI  - Congenital hereditary anomalous coronary artery origin.

PMID- 22608018
TI  - Red cell distribution width measurement: what role does it have in heart failure?

PMID- 22608020
TI  - Crumbs regulates polarity and prevents light-induced degeneration of the simple
      eyes of Drosophila, the ocelli.
AB  - The evolutionary conserved transmembrane protein Crumbs (Crb) regulates
      morphogenesis of photoreceptor cells in the compound eye of Drosophila and
      prevents light-dependent retinal degeneration. Here we examine the role of Crb in
      the ocelli, the simple eyes of Drosophila. We show that Crb is expressed in
      ocellar photoreceptor cells, where it defines a stalk membrane apical to the
      adherens junctions, similar as in photoreceptor cells of the compound eyes. Loss
      of function of crb disrupts polarity of ocellar photoreceptor cells, and results
      in mislocalisation of adherens junction proteins. This phenotype is more severe
      than that observed in mutant photoreceptor cells of the compound eye, and
      resembles more that of embryonic epithelia lacking crb. Similar as in compound
      eyes, crb protects ocellar photoreceptors from light induced degeneration, a
      function that depends on the extracellular portion of the Crb protein. Our data
      demonstrate that the function of crb in photoreceptor development and homeostasis
      is conserved in compound eyes and ocelli and underscores the evolutionarily
      relationship between these visual sense organs of Drosophila. The data will be
      discussed with respect to the difference in apico-basal organisation of these two
      cell types.

PMID- 22608022
TI  - Harm reduction, human rights, and access to information on safer abortion.
AB  - A harm reduction and human rights approach, grounded in the principles of
      neutrality, humanism, and pragmatism, supports women's access to information on
      the safer self- use of misoprostol in diverse legal settings. Neutrality refers
      to a focus on the risks and harms of abortion rather than its legal or moral
      status. Humanism refers to the entitlement of all women to care and concern for
      their lives and health, to be treated with respect, worth, and dignity, and to
      the empowerment of women to participate in decision-making and political action.
      Pragmatism accepts the historical reality that women will engage in unsafe
      abortion, including self-induction, while addressing factors that render them
      vulnerable to this reality, and requires assessment of interventions to reduce
      abortion-related harms on evidence of their real rather than intended effect.
      Criminal law reform is a necessary conclusion to a harm reduction and human
      rights approach.

PMID- 22608021
TI  - In vivo evaluation of PhiC31 recombinase activity in transgenic mice.
AB  - Genome engineering strategies employing site-specific recombinases (SSRs) such as
      Cre, Flp and PhiC31, have become powerful tools to analyze gene function and
      manipulate neural network in vertebrates. In the present study, we evaluated the
      ability of PhiC31 phage integrase to induce genomic recombination in transgenic
      mice. PhiC31 is the integrase encoded by the Streptomyces bacteriophage that
      promotes recombination between heterotypic attP and attB sites. We generated
      transgenic mice that express codon-optimized PhiC31 (PhiC31o) in neural
      stem/progenitor cells or tyrosine hydroxylase (TH) expressing catecholaminergic
      neurons. PhiC31 was functional in these cells and capable of excising a
      transcriptional stop cassette flanked by PhiC31-specific attP/B recognition
      sites. PhiC31-ER(T2), a fusion protein of PhiC31o (without the nuclear
      localization signal) and the mutated ligand-binding domain of the human estrogen
      receptor, was able to induce recombination in neural stem/progenitor cells in a
      tamoxifen-dependent manner, but the recombination rate was less efficient than
      for PhiC31. Thus, PhiC31 integrase is functional in transgenic mice and is
      suitable for mosaic recombination in restricted cell populations.

PMID- 22608023
TI  - Vesicouterine fistula resulting in a vesical pregnancy.

PMID- 22608024
TI  - Comparison of intrapartum outcome among immigrant women from Ethiopia and the
      general obstetric population in Israel.
AB  - OBJECTIVE: To compare intrapartum outcome between ethnic Ethiopian women and the
      general obstetric population in Israel. METHODS: In a retrospective study,
      computerized data from all Ethiopian women who delivered between January 2004 and
      August 2011 at a university teaching hospital in Afula, Israel, were assessed.
      The control group comprised non-Ethiopian Israeli women, who were matched at a
      ratio of 1:2 on the basis of deliveries that took place immediately before and
      after delivery by an Ethiopian woman. The primary outcome was incidence of
      operative delivery. RESULTS: During the study period, 576 Ethiopian women
      delivered along with 1152 matched control women. Ethiopian women had a higher
      incidence of pre-eclampsia (6.8% versus 4.0%, P=0.01) and early postpartum
      hemorrhage (4.3% versus 1.6%, P=0.003) than control women. After adjustment for
      potential confounders, the incidence of vacuum or cesarean delivery was
      significantly higher among Ethiopian than among control women (odds ratio, 1.68;
      95% confidence interval, 1.28-2.20; P=0.002). The incidence of composite major
      perinatal morbidity, including Erb palsy and cord pH less than 7.1, tended to be
      higher among Ethiopian women than among control women (2.3% versus 1.1%;
      P=0.053). CONCLUSION: Although prepartum and intrapartum care are standardized,
      Ethiopian women had a less favorable intrapartum outcome.

PMID- 22608025
TI  - Lack of association between two polymorphisms in the corticotropin-releasing
      hormone gene promoter and preterm birth in a Hispanic population.

PMID- 22608026
TI  - Risk factors for human papillomavirus infection among women in Portugal: the
      CLEOPATRE Portugal Study.
AB  - OBJECTIVE: To investigate demographic, socioeconomic, lifestyle, and medical
      factors that might predispose women to cervical human papillomavirus (HPV)
      infection. METHOD: A cross-sectional population-based study was performed. Women
      aged 18-64 years who attended selected obstetrics and gynecology or sexually
      transmitted disease (STD) clinics in mainland Portugal between February 2008 and
      March 2009 were recruited, according to an age-stratified sampling strategy.
      Liquid-based cytology samples were analyzed centrally for HPV genotype and for
      cytologic features. Univariate and multivariate logistic regression analyses
      identified risk factors for HPV infection. RESULTS: Among the 2326 women
      evaluated, the crude prevalence of HPV infection was 19.4%. Lifetime number of
      sexual partners was a strong predictor of HPV infection (odds ratio 5.44 for 5-10
      partners versus 1 partner; P<0.001). Other risk factors were young age
      (particularly among women aged 20-24 years; P<0.001); country of birth other than
      mainland Portugal (P=0.002); education up to secondary school level (P=0.010);
      smoking history (<= 10 years; P=0.004); and any STD in the past 12 months
      (P=0.052). CONCLUSION: Data from the present study may aid identification of
      women at increased risk of HPV infection and target prevention strategies. TRIAL
      REGISTRATION: National Commission of Data Protection (CNPD) registration number
      5346/2007; Sanofi Pasteur MSD study number HPV-E05.

PMID- 22608027
TI  - The "see and treat" strategy for identifying cytologic high-grade precancerous
      cervical lesions among low-income Brazilian women.
AB  - OBJECTIVE: To evaluate the strategy of "see and treat" by loop electrosurgical
      excision procedure (LEEP) for cytologic high-grade precancerous cervical lesions
      (squamous intraepithelial lesions; HSIL) and post-LEEP recurrence among low
      income Brazilian women. METHODS: In a retrospective survey of women who underwent
      LEEP for cytologic HSIL without prior cervical biopsy between January 2004 and
      March 2008 at CISVALI, Uniao da Vitoria, Parana, Brazil, LEEP sample histology
      and patient follow-up by Papanicolaou smear were assessed. RESULTS: Among 117
      women treated, 24% had no lesions, 67.5% had cervical intraepithelial neoplasia
      (CIN) grade 2/3, and 5.2% had squamous cell carcinoma or adenocarcinoma on LEEP
      histology. Among patients with follow-up, recurrences occurred in those with no
      lesions (16.7%) and CIN 2/3 (25%) (P>0.05). HSIL was the most frequent type of
      recurrence (87%) (P<0.001). In total, 6.3% of patients had positive ectocervical
      (ecto-positive) and endocervical (endo-positive) margins, 3.8% had ecto-positive,
      and 33.0% had endo-positive margins. Recurrences occurred in women with endo
      positive (26.3%), no margin (17.4%), and cautery artifact margin (25.0%)
      involvement (P>0.05). CONCLUSION: For cytologic HSIL, the benefits of the
      strategy of "see and treat" by LEEP outweighed the risk of overtreatment.
      Patients with both positive and negative margins on LEEP should be followed
      carefully.

PMID- 22608028
TI  - Intraocular lens power calculation for humanitarian missions based on partial
      biometry.
AB  - PURPOSE: To determine whether the correlation between corneal power (K) and axial
      length (AL) can be used for intraocular lens (IOL) power calculation when
      biometric data are incomplete. SETTING: Developing regions served by United
      States Navy humanitarian assistance missions. DESIGN: Case series. METHODS:
      Measurements of K and AL were collected from all adult cataract surgery charts
      and used to calculate emmetropic IOL powers. A formula for estimating K or AL was
      derived by Deming regression analysis. The emmetropic IOL powers were calculated
      by hypothetical scenarios as follows: (1) K estimated from the formula and
      measured AL, (2) mean population K and measured AL, (3) measured K and estimated
      AL, and (4) measured K and mean population AL. The mean absolute refractive error
      (MAE) was calculated for each hypothetical scenario and an additional scenario
      (scenario 5) using single IOL power for all eyes. The MAEs were compared with a
      paired t test. RESULTS: The formula derived from Deming regression analysis was K
      = 74.56 - 1.317 * AL. The MAE for the scenarios were (1) 0.90 diopters (D), (2)
      1.11 D, (3) 1.91 D, (4) 1.55 D, and (5) 1.22 D. The MAE for scenario 1 was
      significantly less (P<.01) than that for scenarios 2 and 5. The MAE for scenario
      5 was significantly less than that for scenarios 3 and 4. CONCLUSIONS: The
      correlation between K and AL can be used to improve accuracy of IOL calculation
      when K is unavailable. When the AL is unavailable, the mean population IOL power
      is most accurate. FINANCIAL DISCLOSURE: No author has a financial or proprietary
      interest in any material or method mentioned.

PMID- 22608029
TI  - Transient myopic shift after phakic intraocular lens implantation.
AB  - Three patients presented with spontaneous myopic shift 6 weeks to 6 months after
      implantation of the Artiflex phakic intraocular lens (pIOL). The corrected
      distance visual acuity (CDVA) was maintained in all cases. Cyclopentolate drops
      successfully reverted the myopic shift in all cases; however, 2 cases required
      surgical reenclavation of the pIOL haptics to achieve long-term refractive
      stability. At the last follow-up, all patients had returned to emmetropia, with
      uncorrected distance visual acuities of 20/20. A slight decrease in objective
      optical quality was observed. No eye lost a line of CDVA. In 1 eye, optical
      coherence tomography scans showed slight posterior positioning of the pIOL. These
      cases show that spontaneous myopic shift is a potential complication of iris-claw
      pIOL implantation. That cyclopentolate drops and/or reenclavation of the haptics
      were effective in reverting the situation suggests a mechanical mechanism related
      to iris and ciliary body dynamics. FINANCIAL DISCLOSURE: Dr. Guell is a
      consultant to Ophtec. No author has a financial or proprietary interest in any
      material or method mentioned.

PMID- 22608030
TI  - Higher-order aberrations and visual function in pseudophakic eyes with a toric
      intraocular lens.
AB  - PURPOSE: To compare higher-order aberrations (HOAs) and visual function in eyes
      with a toric intraocular lens (IOL) and eyes with a nontoric IOL. SETTING:
      Hayashi Eye Hospital, Fukuoka, Japan. DESIGN: Case-control study. METHODS: Eyes
      that had phacoemulsification were enrolled in 1 of the following 3 groups: (1)
      preoperative corneal astigmatism of 1.00 diopter (D) with a toric IOL (toric
      group), (2) astigmatism of 1.00 D or more with a nontoric IOL (high-astigmatism
      group), and (3) astigmatism less than 1.00 D with a nontoric IOL (low-astigmatism
      group). Ocular and corneal HOAs were measured using a wavefront analyzer.
      Photopic and mesopic visual acuities at high- to low-contrast visual targets were
      measured using a contrast sensitivity tester. RESULTS: The mean ocular and
      corneal total HOAs and 3rd-order aberrations in the toric and high-astigmatism
      groups tended to be greater than in the low-astigmatism group; HOAs and 3rd-order
      aberrations at 3 months and HOAs at 6 months were significantly different (P
      <=.0403). The mean corrected visual acuity did not differ significantly between
      groups. However, photopic low-contrast visual acuity (LCVA) and mesopic high- to
      low-contrast visual acuity was significantly worse in the toric and high
      astigmatism groups than in the low-astigmatism group (P <=.0210). CONCLUSION:
      Postoperatively, ocular and corneal HOAs were greater in eyes with a toric IOL
      and in eyes with high preexisting corneal astigmatism than in eyes with low
      preexisting astigmatism, which impaired photopic LCVA and mesopic visual acuity.
      FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any
      material or method mentioned.

PMID- 22608031
TI  - The discovery of viruses: advancing science and medicine by challenging dogma.
AB  - The discovery of viruses in the final years of the nineteenth century represented
      the culmination of two decades of work on tobacco mosaic disease by three
      botanical scientists. Eventually their discovery led to a paradigm shift in
      scientific thought, but it took more than 20 years to appreciate its implications
      because it was inconsistent with the prevailing dogma of the time-Koch's
      postulates. Although these 'rules' were actually conceived of as guidelines upon
      which to establish microbial causality and their implementation resulted in many
      new discoveries, they also had the unintended effect of limiting the
      interpretation of novel findings. However, by challenging existing dogma through
      rigorous scientific observation and sheer persistence, the investigators advanced
      medicine and heralded new areas of discovery.

PMID- 22608032
TI  - Using a checklist to identify barriers to compliance with evidence-based
      guidelines for central line management: a mixed methods study in Mongolia.
AB  - OBJECTIVES: This study aimed to determine the extent to which a checklist has
      potential for identifying barriers to compliance with central line management
      guidelines, to evaluate the potential utility of checklists to improve the
      management of central lines in Mongolia, and to define the gap between current
      and best practices. METHODS: A 22-item checklist was developed based on the
      Centers for Disease Control and Prevention (CDC, USA) guidelines and existing
      central line-associated bloodstream infection (CLABSI) checklists. The checklist
      was used to observe 375 central line procedures performed in the intensive care
      units of four tertiary hospitals of Mongolia between July and December 2010. In
      parallel, 36 face-to-face interviews were conducted in six other tertiary
      hospitals to explain practice variations and identify barriers. RESULTS: The
      baseline compliance level across all components of the checklist was 68.5%. The
      main factors explaining low levels of compliance were outdated local standards, a
      lack of updated guidelines, poor control over compliance with existing clinical
      guidelines, poor supply of medical consumables, and insufficient knowledge of
      contemporary infection control measures among health care providers. CONCLUSIONS:
      The health authorities of Mongolia need to adequately address the prevention and
      control of CLABSIs in their hospitals. Updating local standards and guidelines
      and implementing adequate multifaceted interventions with behavioral,
      educational, and logistical components are required. Use of a checklist as a
      baseline evaluation tool was feasible. It described current practice, showed
      areas that need urgent attention, and provided important information needed for
      future planning of CLABSI interventions.

PMID- 22608033
TI  - On the generation and quenching of reactive-oxygen-species by aqueous vitamin B2
      and serotonin under visible-light irradiation.
AB  - It is well known that endogenous daylight-absorbing compounds produce the
      sensitized photodegradation of biologically relevant substrates. In this context
      the photostability of a mixture of the indole neurotransmitter serotonin (Sero)
      and vitamin B2 (riboflavin, Rf) upon visible-light irradiation and the possible
      role of Sero and related compounds as generators or deactivators of reactive
      oxygen species (ROS) was investigated through a kinetic and mechanistic study.
      The work was done at pH 7 and under experimental conditions in which only the
      vitamin absorbs photoirradiation. Tryptamine (Trpa) and 5-hydroxyindole (OHIn)
      were included in the study as model compounds for the neurotransmitter. The
      visible light irradiation of aqueous Rf in the individual presence of Sero, Trpa
      and 5-OHIn, under aerobic conditions, induce degradative processes on the indole
      derivatives (In-der). At least two different mechanisms operate. Our analysis
      shows that the main reaction pathway is an electron-transfer-mediated quenching
      of triplet excited Rf ((3)Rf(*)) by the In-der. It produces the species Rf(
      )/RfH() and the In-der radical cation that could react to form phenoxy and alpha
      amino radicals. In a further reaction step the species O(2)(-) and OH() could be
      produced. In parallel, energy transfer from (3)Rf(*) to dissolved oxygen would
      generate O(2)((1)Delta(g)). Within the frame of the proposed mechanism, results
      suggest that Rf-sensitized degradation of Sero occurs via the mentioned ROS and
      non-oxygenated radical-mediated processes. The indole compound quenches
      O(2)((1)Delta(g)) in a dominant physical fashion. This fact constitutes a
      desirable property in antioxidants, provided that the quenching process
      practically does not eliminate the scavenger. Sero exerts a photoprotective
      effect towards tryptophan through the combined quenching of O(2)((1)Delta(g)) and
      (3)Rf(*), the latter excited species responsible for the generation of ROS. The
      amino acid can be taken as a target model of oxidizable biological substrates,
      particularly proteins.

PMID- 22608034
TI  - A stepwise progression in the treatment of cardiogenic shock.
AB  - Cardiogenic shock remains a deadly complication of acute myocardial infarction
      (MI). Early revascularization, inotropic support, and intraaortic balloon
      counterpulsation are the mainstays of treatment, but these are not always
      sufficient. New mechanical approaches, both percutaneous and surgical, are
      available in this high-risk population. We present a case of a young woman with a
      massive anterior wall MI and subsequent cardiogenic shock who was treated with
      advanced mechanical circulatory support. This case serves as an illustration of
      the stepwise escalation of mechanical support that can be applied in a patient
      with an acute MI complicated by refractory cardiogenic shock. We also review the
      literature with regard to the use of percutaneous left ventricular assist devices
      in the setting of cardiogenic shock.

PMID- 22608036
TI  - Invited commentary.

PMID- 22608035
TI  - Sense of coherence is associated with reduced psychological responses to job
      stressors among Japanese factory workers.
AB  - BACKGROUND: Job stress is associated with adverse health effects. The present
      study was conducted to examine the association between sense of coherence (SOC),
      as advocated by Antonovsky, and psychological responses to job stressors among
      Japanese workers. METHODS: A self-administered questionnaire containing a
      Japanese version of the 13-item SOC scale, the Brief Job Stress Questionnaire,
      and a self-rated health item were distributed to 1968 workers in X Prefecture.
      Anonymous responses were recovered by postal mail. RESULTS: Complete responses
      were received from 299 workers (response rate 15.2%, 191 males and 108 females)
      who consented to participate in the study. Participants were 186 office clerks,
      38 sales representatives, 22 technical engineers, 16 service trade workers, eight
      information processing workers, eight technical experts, and 21 other workers of
      various types. SOC scores were associated with age, self-rated health, job title,
      and marriage status. According to regression analyses stratified by gender, SOC
      was inversely associated with tension, fatigue, anxiety, depression and
      subjective symptoms in males, and tension, depression and subjective symptoms in
      females. SOC was positively associated with vigor in both males and females.
      CONCLUSIONS: Having a strong SOC may reduce worker's negative job stress
      responses and increase their vigor. Longitudinal studies are required to confirm
      this finding.

PMID- 22608037
TI  - Invited commentary.

PMID- 22608038
TI  - Invited commentary.

PMID- 22608039
TI  - Outcomes and practice patterns in patients undergoing lower extremity bypass.
AB  - BACKGROUND: The appropriate application of endovascular intervention vs bypass
      for both critical limb ischemia (CLI) and intermittent claudication (IC) remains
      controversial, and outcomes from large, contemporary series are critical to help
      inform treatment decisions. Therefore, we sought to define the early and 1-year
      outcomes of lower extremity bypass (LEB) in a large, multicenter regional cohort,
      and analyze trends in the use of LEB with or without prior endovascular
      interventions. METHODS: The Vascular Study Group of New England database was used
      to identify all infrainguinal LEB procedures performed between 2003 and 2009. The
      primary study endpoint was 1-year amputation-free survival (AFS). Secondary
      endpoints included in-hospital mortality and morbidity, including major adverse
      cardiac events. Trend analyses were conducted to identify annual trends in the
      proportion of LEBs performed for an indication of IC, in-hospital outcomes,
      including mortality and morbidity, and 1-year outcomes, including AFS. Analyses
      were performed on the entire cohort and then stratified by indication. RESULTS:
      Between 2003 and 2009, 2907 patients were identified who underwent LEBs (72% for
      CLI; 28% for IC). The proportion that underwent LEB for IC increased
      significantly over the study period (from 19% to 31%; P < .0001). There was a
      significant increase over time in the proportion of LEBs performed after a
      previous endovascular intervention among both CLIs (from 11% to 24%; P < .0001)
      and ICs (from 13% to 23%; P = .02). Neither in-hospital mortality nor cardiac
      event rates changed significantly among either group. There was no significant
      change in 1-year AFS in patients with IC (97% in 2003 and 98% in 2008; P for
      trend .63) or in patients with CLI (73% in 2003 and 81% in 2008; P = .10).
      CONCLUSIONS: Over the last 7 years, significant changes in patient selection for
      LEBs have occurred in New England. The proportion of LEBs performed for ICs as
      opposed to CLIs has increased. Patients are much more likely to have undergone
      prior endovascular interventions before undergoing a bypass. In-hospital and 1
      year outcomes after LEB for both IC and CLI have remained excellent with no
      significant changes in AFS.

PMID- 22608040
TI  - Outcome of endovascular repair of popliteal artery aneurysm using the Viabahn
      endoprosthesis.
AB  - OBJECTIVE: This study reviews a single-center experience of endovascular
      popliteal aneurysm (PAA) repair. METHODS: A retrospective review was performed to
      identify all endovascular PAA repairs performed between September 2004 and
      January 2011. RESULTS: We identified 21 patients (mean age, 74 +/- 9 years, 91%
      men) with PAAs (mean size, 2.89 +/- 1.0 cm) in 26 limbs, of which 38% were
      symptomatic. All patients underwent endovascular repair with a Viabahn covered
      stent graft (W. L. Gore & Assoc, Inc, Flagstaff, Ariz). Postoperatively, all
      patients were maintained on antiplatelet therapy with clopidogrel or aspirin, or
      both. Mean follow-up was 22 +/- 17 months (range, 1-57 months). One patient with
      one aneurysm was lost to follow-up. Primary and secondary patencies were both
      91.2% at 1 year and were 85.5% and 91.2%, respectively, at 2 years. The limb
      salvage rate was 100%. Four stent graft failures occurred at a mean of 12.3 +/-
      11 months. One technical failure due to stent graft infolding required conversion
      to an open femoral-popliteal bypass. Three additional graft failures occurred in
      patients with poor (single-vessel) runoff. Compared with patients with two- or
      three-vessel runoff, the graft failure rate in patients with single-vessel runoff
      was statistically significant (P = .02). Two of the graft failures were
      successfully treated with open thrombectomy, and one required a tibial artery
      bypass for limb salvage. CONCLUSIONS: Endovascular repair of PAAs is feasible and
      has acceptable midterm patency rates. Poor distal runoff predicted graft failure.

PMID- 22608042
TI  - Large arteriovenous fistula between the common iliac artery and the vein after
      blunt trauma.

PMID- 22608041
TI  - The Walking Impairment Questionnaire stair-climbing score predicts mortality in
      men and women with peripheral arterial disease.
AB  - OBJECTIVE: The Walking Impairment Questionnaire (WIQ) measures self-reported
      walking distance, walking speed, and stair-climbing ability in men and women with
      lower extremity peripheral arterial disease (PAD). We determined whether poorer
      WIQ scores are associated with higher all-cause and cardiovascular disease (CVD)
      mortality in individuals with and without PAD. METHODS: We identified 1048 men
      and women with and without PAD from Chicago-area medical centers. Participants
      completed the WIQ at baseline and were monitored for a median of 4.5 years. Cox
      proportional hazards models were used to relate baseline WIQ scores with death,
      adjusting for age, sex, race, the ankle-brachial index (ABI), comorbidities, and
      other covariates. RESULTS: During follow-up, 461 participants (44.0%) died,
      including 158 deaths from CVD. PAD participants in the lowest baseline quartile
      of the WIQ stair-climbing scores had higher all-cause mortality (hazard ratio,
      1.70; 95% confidence interval, 1.08-2.66, P = .02) and higher CVD mortality
      (hazard ratio, 3.11; 95% confidence interval, 1.30-7.47, P = .01) compared with
      those with the highest baseline WIQ stair-climbing score. Among PAD participants,
      there were no significant associations of lower baseline WIQ distance or speed
      scores with rates of all-cause mortality (P = .20 and P = .07 for trend,
      respectively) or CVD mortality (P = .51 and P = .33 for trend, respectively).
      Among non-PAD participants there were no significant associations of lower
      baseline WIQ stair-climbing, distance, or speed score with rates of all-cause
      mortality (P = .94, P = .69, and P = .26, for trend, respectively) or CVD
      mortality (P = .28, P = .68, and P = .78, for trend, respectively). CONCLUSIONS:
      Among participants with PAD, lower WIQ stair-climbing scores are associated with
      higher all-cause and CVD mortality, independently of the ABI and other
      covariates.

PMID- 22608043
TI  - A primer on cost-effectiveness analyses for vascular surgeons.
AB  - The rate of growth in health care costs in the United States is simply
      unsustainable. In this economic climate, health care providers will increasingly
      be asked to justify the existence of health care programs and management
      strategies on an economic basis. An understanding of cost-effectiveness analyses
      and its components - direct and indirect costs, quality-adjusted life-years, and
      incremental cost-effectiveness ratios - is integral to this. We present a primer
      on the methodology of cost-effectiveness analyses and a review of published cost
      effectiveness analyses of vascular surgery interventions with the goal of
      providing the vascular surgeon with a basic understanding of this topic.

PMID- 22608044
TI  - When is medical industry backing lacking?
AB  - A sales representative from Megastint approached Dr A. Krasia with an offer to
      financially support future educational conferences and allow his institution to
      be a training center if he participates in a new study comparing an old product
      to a recently approved and more expensive one. Dr Krasia and his department
      currently use Megastint's products. The medical center's utilization committee
      must approve the addition of more expensive pharmaceuticals, devices, or
      equipment, and Dr Krasia is the chair. How should Dr Krasia respond to
      Megastint's offer of financial support and to become a training center?

PMID- 22608045
TI  - Medical care manifesto.

PMID- 22608046
TI  - The impact of endovascular procedures on fellowship training in lower extremity
      revascularization.
AB  - OBJECTIVE: The introduction of endovascular aneurysm repair has resulted in a
      decline in open abdominal aortic aneurysm repairs performed by vascular
      residents. The purpose of this study was to evaluate if a similar trend has
      occurred with open lower extremity revascularization procedures, with increased
      endovascular procedures producing a decrease in the number of open lower
      extremity revascularizations. Furthermore, this study evaluates the effect of
      endovascular procedure volume on the frequency of subtypes of open lower
      extremity procedures performed. METHODS: The total number of vascular procedures,
      lower extremity bypasses, and endovascular interventions from 2000 to 2010 were
      analyzed from case logs of vascular residents as reported by the Accreditation
      Council for Graduate Medical Education. RESULTS: The average number of cases
      performed by vascular residents has increased by 150% from 463.9 in 2000 to 1168
      in 2009, due to the increased number of endovascular procedures. The average
      number of endovascular revascularizations has increased by 317% from 40.5
      performed in 2000 to 168.9 in 2009. Femoral-popliteal bypasses have increased in
      frequency by 27% whereas the number of infrapopliteal bypass has remained
      unchanged. The largest difference is seen in femoral endarterectomies with a 234%
      increase from 3.2 per resident in 2001 to 10.7 per resident in 2010. Comparison
      of the proportion of femoral-popliteal and tibioperoneal interventions performed
      by angioplasty or bypass after 2007 revealed that endovascular interventions
      comprise 50% of procedures in the femoral-popliteal distribution, whereas 65% of
      infrapopliteal interventions are still performed using open techniques.
      CONCLUSIONS: The number of procedures performed during vascular residency has
      dramatically increased over the last decade secondary to the increased number of
      endovascular procedures. The average vascular surgery resident's open operative
      experience has been stable over the last 10 years, despite the increasing
      endovascular case volume. Residents perform femoral endarterectomy with
      increasing frequency, perhaps representing an increasing volume of hybrid
      procedures. Gaps in information available for evaluating resident training remain
      a significant obstacle. Moving forward, revision of the current reporting system
      to a format that more accurately reflects resident experience would be
      beneficial.

PMID- 22608047
TI  - Invited commentary.

PMID- 22608048
TI  - Breakthrough: Arthur Blakemore and Arthur Voorhees, Jr.

PMID- 22608050
TI  - Regarding "Impact of practice patterns in shunt use during carotid endarterectomy
      with contralateral carotid occlusion".

PMID- 22608052
TI  - Predictors of recurrence in bipolar disorders in Spain (PREBIS study data).
AB  - OBJECTIVE: The objective of this study was to evaluate demographic, psychosocial
      and clinical predictors of mood recurrences in bipolar disorder (BD) euthymic
      outpatients followed-up for 12 months in a naturalistic setting. METHODS: The
      study included 595 consecutive BD patients, diagnosed according to DSM-IV-TR
      criteria, in clinical remission at baseline. Quarterly assessments were
      scheduled. Clinical evaluation as well as mood and functioning psychometric
      evaluations were performed. We applied logistic regression analysis to determine
      predictors of presenting an affective recurrence, and Cox regression analysis to
      examine the association between individual predictors and time to affective
      recurrence. RESULTS: Of the 593 patients finally included (60% women, 84.5% BD
      I), 141 (23.78%) had at least a recurrence during the 12 months follow-up. Time
      until 25% of the patients experienced a recurrence was 12 months (95% CI: 9.14
      undetermined). In multivariate analysis, factors significantly related to relapse
      were living setting (p=0.002) and total number of previous episodes (p=0.01).
      Residents in mixed urban/rural catchment areas had 57% more risk than dwellers of
      cities with more than 100,000 people, and a higher number of previous episodes
      also increased the relapse risk. A shorter time to relapse was related to job
      status (p=0.004) and to living setting (p=0.002). CONCLUSION: In our sample,
      living in environments of less than 100,000 inhabitants and having more previous
      affective episodes were related to an increased relapse risk in BD, and job
      status and living setting were related to a shorter time to relapse. LIMITATIONS:
      No specific contemporary practice guidelines were used. Drug treatment and plasma
      levels, although measured, were not registered.

PMID- 22608053
TI  - Suicide news reporting accuracy and stereotyping in Hong Kong.
AB  - BACKGROUND: The mass media are often criticized for oversimplifying the causes of
      suicide and overlooking some of the risk factors. However, there is a lack of
      empirical evidence to support this assertion. The study aims to examine the
      accuracy of news reports in Hong Kong (HK) and in particular whether or not such
      reports stereotype victims according to gender and suicide method. METHODS: Data
      from a case-control psychological autopsy (PA) study of 150 HK suicides were
      utilized. The reports of the PA cases from five major HK newspapers were
      collected and reviewed to identify whether or not there was a match in terms of
      the cases' profile and risk factors. RESULTS: The age, gender, and method of the
      suicides were largely reported correctly (>70%) but accounts of risk factors were
      seldom accurate (<46%). No significant difference was found between tabloid- and
      non-tabloid-type newspapers' accuracy. Media stereotyping of gender-specific
      suicide and charcoal-burning suicide was identified. LIMITATIONS: The study was
      based on a HK sample so the findings are not necessarily applicable elsewhere.
      CONCLUSIONS: The HK mass media generally demonstrated poor accuracy in reporting
      suicide risk factors. Their reporting was also problematic in terms of
      stereotyping gender- and method-specific suicides. Clinical practitioners should
      be alerted to these findings when working with the media. They can also adopt
      this novel usage of PA data to extract further information from other PA studies
      and thereby broaden the investigation of reporting accuracy and stereotyping of
      suicide to more diverse social contexts.

PMID- 22608054
TI  - Trichomonas vaginalis antimicrobial drug resistance in 6 US cities, STD
      Surveillance Network, 2009-2010.
AB  - Nitroimidazoles (metronidazole and tinidazole) are the only recommended drugs for
      treating Trichomonas vaginalis infection, and previous samples that assessed
      resistance of such isolates have been limited in geographic scope. We assessed
      the prevalence of in vitro aerobic metronidazole and tinidazole resistance among
      T. vaginalis isolates from multiple geographic sites in the United States. Swab
      specimens were obtained from women who underwent routine pelvic examinations at
      sexually transmitted disease clinics in 6 US cities. Cultured T. vaginalis
      isolates were tested for nitroimidazole resistance (aerobic minimum lethal
      concentration [MLC] >50 ug/mL). Of 538 T. vaginalis isolates, 23 (4.3%) exhibited
      low-level in vitro metronidazole resistance (minimum lethal concentrations 50-100
      ug/mL). No isolates exhibited moderate- to high-level metronidazole resistance or
      tinidazole resistance. Results highlight the possibility that reliance on a
      single class of antimicrobial drugs for treating T. vaginalis infections may
      heighten vulnerability to emergence of resistance. Thus, novel treatment options
      are needed.

PMID- 22608055
TI  - Effect of bariatric surgery-induced weight loss on renal and systemic
      inflammation and blood pressure: a 12-month prospective study.
AB  - BACKGROUND: Bariatric surgery improves arterial hypertension and renal function;
      however, the underlying mechanisms and effect of different surgical procedures
      are unknown. In the present prospective study, we compared the 12-month follow-up
      results after Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding,
      and laparoscopic sleeve gastrectomy on weight loss, hypertension, renal function,
      and inflammatory status. METHODS: A total of 34 morbidly obese patients were
      investigated before, one and 12 months after Roux-en-Y gastric bypass (n = 10),
      laparoscopic adjustable gastric banding (n = 13), and laparoscopic sleeve
      gastrectomy (n = 11) for hypertension, kidney function, urinary and serum
      cytokine levels of macrophage migration inhibitory factor, monocyte chemotactic
      protein-1, and chemokine ligand-18. RESULTS: At 12 months after surgery, the
      patients in all 3 treatment arms showed a significant decrease in the mean body
      mass index, mean arterial pressure, and urinary and serum inflammatory markers
      (all P < .001). The reduction in urinary and serum cytokine levels correlated
      directly with body weight loss (P < .05). Patients with impaired renal function
      at baseline (corresponding to serum cystatin C >.8 mg/L) had a marked improvement
      in renal function 12 months after surgery (P < .05). CONCLUSION: Surgically
      induced weight loss is associated with a marked decrease in renal and systemic
      inflammation and arterial hypertension and improvement in renal function in
      patients with pre-existing renal impairment. These effects appear to be
      independent of surgical procedure. The improvement in renal inflammation could be
      1 of the mechanisms contributing to the beneficial effects of bariatric surgery
      on arterial blood pressure, proteinuria, and renal function.

PMID- 22608056
TI  - Is bariatric surgery safe in patients who refuse blood transfusion?
AB  - BACKGROUND: A small, but significant, number of patients undergoing bariatric
      surgery refuse blood transfusion for religious or other personal reasons.
      Jehovah's Witnesses number more than 1 million members in the United States
      alone. The reported rates of hemorrhage vary from .5% to 4% after bariatric
      surgery, with transfusion required in one half of these cases. Pharmacologic
      prophylaxis against venous thromboembolism could further increase the
      perioperative bleeding risk. Our objective was to report the perioperative
      outcomes of bariatric surgery who refuse blood transfusion at a bariatric center
      of excellence, private practice in the United States. METHODS: A retrospective
      review of all patients who refused blood transfusion when undergoing bariatric
      surgery during a 10-year period was conducted. Patients were identified from a
      prospectively maintained database by the bloodless surgery program at Legacy Good
      Samaritan Hospital. Data were collected on demographics, co-morbidities,
      laboratory values, medication use, blood loss, and 30-day complications. RESULTS:
      Thirty-five bloodless surgery patients underwent bariatric surgery from 2000 to
      2009. Of these 35 patients, 21 underwent laparoscopic adjustable gastric banding
      and 14 Roux-en-Y gastric bypass. Before 2006, only pneumatic compression devices
      were applied for venous thromboembolism prophylaxis (n = 6). Subsequently,
      combination venous thromboembolism prophylaxis was performed with fondaparinux
      sodium 2.5 mg for RYGB or enoxaparin 40 mg for LAGB (n = 29). One RYGB patient
      developed postoperative hemorrhage requiring reoperation. No venous
      thromboembolisms or deaths occurred. CONCLUSION: Bariatric surgery can be
      performed in patients who refuse blood transfusion with acceptable postoperative
      morbidity. Larger studies are necessary to confirm the safety of this approach
      and to examine the effect of pharmacologic thromboprophylaxis in this patient
      group.

PMID- 22608057
TI  - Mangrove plant, Rhizophora mucronata (Lamk, 1804) mediated one pot green
      synthesis of silver nanoparticles and its antibacterial activity against aquatic
      pathogens.
AB  - BACKGROUND: Biosynthesis of nanoparticles has received increasing attention due
      to the growing need to develop safe, time-effective and environmentally friendly
      technologies for nano-materials synthesis. This paper reports the one pot green
      synthesis of silver nanoparticles (AgNPs) using the leaf bud extract of a
      mangrove plant, Rhizophora mucronata and their antimicrobial effects against
      aquatic pathogens. Highly stable AgNPs were synthesized by treating the mangrove
      leaf bud extract with aqueous silver nitrate solution at 15 psi pressure and 121
      degrees C for 5 minutes. RESULTS: The biosynthesized AgNPs were characterized by
      UV-visible spectrum, at 426 nm. The X-Ray Diffraction (XRD) pattern revealed the
      face-centered cubic geometry of AgNPs. Fourier Transform Infra Red (FTIR)
      spectroscopic analysis was carried out to identify the possible biomolecules
      responsible for biosynthesis of AgNPs from the leaf bud extract. The size and
      shape of the well-dispersed AgNPs were documented with the help of High
      Resolution Transmission Electron Microscopy (HRTEM) with a diameter ranged from 4
      to 26 nm. However a maximum number of particles were observed at 4 nm in size.
      The antibacterial effects of AgNPs were studied against aquatic pathogens Proteus
      spp., Pseudomonas fluorescens and Flavobacterium spp., isolated from infected
      marine ornamental fish, Dascyllus trimaculatus. CONCLUSION: This study reveals
      that the biosynthesized AgNPs using the leaf bud extract of a mangrove plant (R.
      mucronata) were found equally potent to synthetic antibiotics. The size of the
      inhibition zone increases when the concentration of the AgNPs increased and
      varies according to species.

PMID- 22608058
TI  - Human papillomavirus in invasive cervical cancer and cervical intraepithelial
      neoplasia 2 and 3 in Venezuela: a cross-sectional study.
AB  - BACKGROUND: This study investigated the distribution of human papillomavirus
      (HPV) types in invasive cervical cancer (ICC), cervical intraepithelial neoplasia
      2 (CIN2) and cervical intraepithelial neoplasia 3 (CIN3) in Venezuela. METHODS:
      Paraffin-embedded samples from 329 women from 29 medical centers of the 24 states
      of Venezuela were analyzed to determine the distribution of HPV types for ICC,
      CIN2, and CIN3, the prevalence of single and multiple infection, and the
      association of HPV types with severity of lesion, comparing CIN2 versus CIN3+
      (CIN3 and ICC). The samples were analyzed with the polymerase chain reaction
      (PCR) followed by reverse hybridization for the identification of HPV types.
      RESULTS: HPV was identified in 95/96 ICC specimens (98.9%), in 142/149 CIN3
      (95.3%) and in 78/84 CIN2 samples (92.8%). The most common types for ICC and CIN3
      were: HPV16, 18, 31, and 33, and for CIN2 were HPV16, 31, 51, 52, and 18. HPV
      single infection was found in 82.1% of ICC cases, in 79.4% of CIN2 cases, and in
      77.4% of CIN3 cases. HPV16 was identified as a single infection more frequently
      in women with CIN3+ than in those with CIN2 (68.6% versus 46.7%, P=0.002), and
      HPV16 or HPV18 types were more prevalent in CIN3+ than in CIN2 (73.4% versus 50%,
      P=0.0006). CONCLUSION: this is the first study of the distribution of HPV types
      in ICC, CIN2, and CIN3 conducted throughout the territory of Venezuela. HPV16 and
      HPV18 were the most frequent HPV types identified in single and multiple
      infections in both ICC and CIN3 groups, and are associated with severity of
      lesion. The knowledge of the distribution of HPV types would allow organization
      of an HPV-DNA-based screening test, and consideration of the implementation of
      prophylactic vaccination in Venezuela.

PMID- 22608059
TI  - Chronic immune activation is a distinguishing feature of liver and PBMC gene
      signatures from HCV/HIV coinfected patients and may contribute to hepatic
      fibrogenesis.
AB  - Hepatitis C virus/human immunodeficiency virus (HCV/HIV) coinfected patients
      demonstrate accelerated progression to severe liver injury in comparison to HCV
      monoinfected patients, although the underlying mechanisms are unclear owing to
      infection of separate tissue compartments with two distinct viral pathogens.
      Microarray analysis of paired liver biopsy and peripheral blood mononuclear cell
      (PBMC) specimens from HCV/HIV coinfected and HCV monoinfected patients identified
      a gene expression signature associated with increased inflammation and immune
      activation that was present only in liver and PBMC samples from coinfected
      patients. We also identified in these samples liver- and PBMC-specific signatures
      enriched with fibrogenic/hepatic stellate activation and proinflammatory genes,
      respectively. Finally, Bayesian networks were constructed by assimilating these
      data with existing data from liver and PBMC samples from other cohorts,
      augmenting enrichment of biologically important pathways and further indicating
      that chronic immune activation in HCV/HIV coinfection may exacerbate liver
      disease progression in coinfected patients.

PMID- 22608060
TI  - Temperature and density dependent induction of a cytopathic effect following
      infection with non-cytopathic HAV strains.
AB  - Hepatitis A virus infection and growth in cultured cells is protracted, cell-type
      restricted, and generally not accompanied by the appearance of a cytopathic
      effect, with the exception of some culture-adapted strains. We demonstrate that
      the non-cytopathic HAV strain HM175/clone 1 can be induced to exhibit a
      cytopathic phenotype in both persistently or acutely infected cells under co
      dependent conditions of lower incubation temperature (<34 degrees C) and reduced
      cell density in both monkey (FRhK-4) and human (A549) cells. This phenotype is
      not virus-strain restricted, as it was also observed in cells infected with HAV
      strains, HAS-15 and LSH/S. Cytopathic effect was accompanied by rRNA cleavage,
      indicating activation of the RNase L pathway, viral negative strand synthesis,
      caspase-3 activation, and apoptosis. The results indicate that a cytopathic
      phenotype may be present in some HAV strains that can be induced under
      appropriate conditions, suggesting the potential for development of a plaque
      assay for this virus.

PMID- 22608062
TI  - Differentiation between malignant and benign solitary pulmonary nodules: use of
      volume first-pass perfusion and combined with routine computed tomography.
AB  - PURPOSE: To evaluate the capability of first-pass volume perfusion computed
      tomography (PCT) for differentiation of solitary pulmonary nodules (SPNs) and to
      compare that of combination of PCT and routine CT with CT alone for the
      differentiation. MATERIALS AND METHODS: Our institutional review board approved
      this study and informed consent was obtained. With nine excluded, 65 consecutive
      patients having a SPN with histopathologic proof or follow-up underwent a 30s PCT
      using the deconvolution model were evaluated. Kruskal-Wallis tests and receiver
      operating characteristics (ROC) analysis were underwent. Four radiologists
      assessed nodules independently and retrospectively. Diagnostic capability was
      compared for CT alone and PCT plus CT. ROC analysis, McNemar test, and weighted
      kappa statistics were performed. RESULTS: Significant differences were found in
      parameters between malignant and benign nodules (p<0.0001 for blood flow, blood
      volume, and permeability surface area product), SPNs were more likely to be
      malignant by using threshold values of more than 55 ml/100 g/min, 2.5 ml/100 g,
      and 10 ml/100 g/min, respectively. PCT plus CT was significantly better in
      overall sensitivity (93%, p=0.004) and accuracy (94%, p=0.003) compared to CT
      alone, not specificity (96%). Area under the curve for ROC analyses of PCT plus
      CT was significantly larger than that of CT alone (p=0.018). Mean weighted kappa
      for PCT plus CT was 0.715, that for CT alone was 0.447. CONCLUSION: Volume first
      pass PCT can distinguish SPNs. Using PCT plus routine CT may be more sensitive
      and accurate for differentiating malignant from benign nodules than CT alone and
      allows more confidence and constancy.

PMID- 22608061
TI  - Characterization of a peptide domain within the GB virus C envelope glycoprotein
      (E2) that inhibits HIV replication.
AB  - GB virus C (GBV-C) infection is associated with prolonged survival in HIV
      infected cohorts, and GBV-C E2 protein inhibits HIV entry when added to CD4+ T
      cells. To further characterize E2 effects on HIV replication, stably transfected
      Jurkat cell lines expressing GBV-C E2 or control sequences were infected with HIV
      and replication was measured. HIV replication (all 6 isolates studied) was
      inhibited in all cell lines expressing a region of 17 amino acids of GBV-C E2,
      but not in cell lines expressing E2 without this region. In contrast, mumps and
      yellow fever virus replication was not inhibited by E2 protein expression.
      Synthetic GBV-C E2 17mer peptides did not inhibit HIV replication unless they
      were fused to a tat-protein-transduction-domain (TAT) for cellular uptake. These
      data identify the region of GBV-C E2 protein involved in HIV inhibition, and
      suggest that this GBV-C E2 peptide must gain entry into the cell to inhibit HIV.

PMID- 22608063
TI  - Quality assessment of out sourced after-hours computed tomography teleradiology
      reports in a Central London University Hospital.
AB  - The study was designed to assess the quality of out sourced after-hours computed
      tomography teleradiology service reports. We evaluated 1028 patients over a time
      period of five month in 2009/2010 (437 female, 591 male, mean age: 51 years,
      range: 0-97 years) who were referred either by the A&E or other in house
      departments from 7 pm to 8 am for different reasons. Reporting was done by a
      teleradiology service provider located in the UK and Australia. Reports were
      assessed during the routinely performed morning meeting by a panel of in house
      radiologists. Assessment was done by a five point agreement scale (5="No
      disagreement", 1="...unequivocal potential for serious morbidity or threat to
      life"). In 811 (79%) patients no disagreement was found, 164 (16%) were rated as
      category 4, 40 (4%) as category 3 ("...likelihood of harm is low"). In 13 (1.3%)
      patients a decision of category 2 was made ("...strong likelihood of moderate
      morbidity but not threat to life"). No category 1 decision was made. As this was
      just a discrepancy decision, a follow up of the category 2 patients was done over
      a period of a maximum of 6 months. In 8 (0.8%) patients the in house reports were
      correct, in 2 (0.2%) patients the teleradiology service provider was right and in
      3 (0.3%) patients the final diagnoses remained unclear. In conclusion there was a
      small rate (0.8%) of proven serious misinterpretations by the teleradiology
      service provider, but these were less than in comparable studies with preliminary
      in house staff reports (1.6-24.6%).

PMID- 22608064
TI  - Variability of sclerosis along the longitudinal hippocampal axis in epilepsy: a
      post mortem study.
AB  - Detailed neuropathological studies of the extent of hippocampal sclerosis (HS) in
      epilepsy along the longitudinal axis of the hippocampus are lacking. Neuroimaging
      studies of patients with temporal lobe epilepsy support that sclerosis is not
      always localised. The extent of HS is of relevance to surgical planning and poor
      outcomes may relate to residual HS in the posterior remnant. In 10 post mortems
      from patients with long histories of drug refractory epilepsy and 3 controls we
      systematically sampled the left and right hippocampus at seven coronal anatomical
      levels along the body to the tail. We quantified neuronal densities in CA1 and
      CA4 subfields at each level using Cresyl Violet (CV), calretinin (CR), calbindin
      (CB) and Neuropeptide Y (NPY) immunohistochemistry. In the dentate gyrus we
      graded the extent of granule cell dispersion, patterns of CB expression, and
      synaptic reorganisation with CR and NPY at each level. We identified four
      patterns of HS based on patterns of pyramidal and interneuronal loss and dentate
      gyrus reorganisation between sides and levels as follows: (1) symmetrical HS with
      anterior-posterior (AP) gradient, (2) symmetrical HS without AP gradient, (3)
      asymmetrical HS with AP gradient and (4) asymmetrical cases without AP gradient.
      We confirmed in this series that HS can extend into the tail. The patterns of
      sclerosis (classical versus atypical or none) were consistent between all levels
      in less than a third of cases. In conclusion, this series highlights the
      variability of HS along the longitudinal axis. Further studies are required to
      identify factors that lead to focal versus diffuse HS.

PMID- 22608065
TI  - Poor attention rather than hyperactivity/impulsivity predicts academic
      achievement in very preterm and full-term adolescents.
AB  - BACKGROUND: Very preterm (VP) children are at particular risk for attention
      deficit/hyperactivity disorder (ADHD) of the inattentive subtype. It is unknown
      whether the neurodevelopmental pathways to academic underachievement are the same
      as in the general population. This study investigated whether middle childhood
      attention or hyperactivity/impulsivity problems are better predictors of VP
      adolescents' academic achievement. METHOD: In a geographically defined
      prospective whole-population sample of VP (<32 weeks gestation) and/or very low
      birth weight (<1500 g birth weight) (VLBW/VP; n = 281) and full-term control
      children (n = 286) in South Germany, ADHD subtypes were assessed at 6 years 3
      months and 8 years 5 months using multiple data sources. Academic achievement was
      assessed at 13 years of age. RESULTS: Compared with full-term controls, VLBW/VP
      children were at higher risk for ADHD inattentive subtype [6 years 3 months: odds
      ratio (OR) 2.8, p < 0.001; 8 years 5 months: OR 1.7, p = 0.020] but not for ADHD
      hyperactive-impulsive subtype (6 years 3 months: OR 1.4, p = 0.396; 8 years 5
      months: OR 0.9, p = 0.820). Childhood attention measures predicted academic
      achievement in VLBW/VP and also full-term adolescents, whereas
      hyperactive/impulsive behaviour did not. CONCLUSIONS: Attention is an important
      prerequisite for learning and predicts long-term academic underachievement. As
      ADHD inattentive subtype and cognitive impairments are frequent in VLBW/VP
      children, their study may help to identify the neurofunctional pathways from
      early brain development and dysfunction to attention problems and academic
      underachievement.

PMID- 22608066
TI  - Rickettsia conorii Indian tick typhus strain and R. slovaca in humans, Sicily.

PMID- 22608067
TI  - The clinical significance of large placental lakes.
AB  - OBJECTIVE: The aim of our study was to establish whether there is a correlation
      between the size of placental lakes and adverse pregnancy outcome. STUDY DESIGN:
      Target ultrasonography for diagnosis of placental lake was performed in the 2nd
      trimester of pregnancy and followed up in the 3rd trimester. Placental lakes were
      defined as homogenous sonolucent avillous lesions greater than 2 cm * 2 cm in
      diameter. The 109 pregnant women enrolled in this study were divided into four
      groups according to the size and change in size of placental lakes. Clinical
      characteristics and pregnancy outcomes in each group were compared. RESULTS: Some
      placental lakes decreased and disappeared, whereas others persisted. There were
      no significant differences in clinical characteristics among the four
      investigated groups. Fetal small-for-gestational-age status was significantly
      correlated with large placental lakes, compared to small. CONCLUSION: Large
      placental lakes were correlated with the fetal status of small for gestational
      age. Therefore, if a large placental lake is identified in the 2nd trimester of
      pregnancy, appropriate surveillance should be considered for the remainder of the
      pregnancy.

PMID- 22608068
TI  - Buspirone: what is it all about?
AB  - Buspirone is an anxiolytic drug and is a partial agonist for the serotonin 5
      HT(1A) receptors as well as possessing low affinity and is an antagonist for the
      dopamine D(2) autoreceptors, with some evidence of a weak affinity to 5-HT(2)
      receptors. The underlying mechanism of action of buspirone is not clear; however
      it is thought that its main pharmacology is mediated via the 5-HT(1A) receptors.
      Initially developed for use in the treatment of generalised anxiety disorder, it
      appears that buspirone may be useful in various other neurological and
      psychiatric disorders, such as attenuating side effects of Parkinson's disease
      therapy, ataxia, depression, social phobia, and behaviour disturbances following
      brain injury, and those accompanying Alzheimer's disease, dementia and attention
      deficit disorder. Considering the potential of this drug to be included in the
      management of many conditions, thorough and controlled studies are required to
      elucidate the exact mechanism of action. This review will consider the evidence
      so far for both the potential underlying mechanisms and its use in various
      conditions.

PMID- 22608069
TI  - Temporal change in NMDA receptor signaling and GABAA receptor expression in rat
      caudal vestibular nucleus during motion sickness habituation.
AB  - Repeated exposure to a provocative motion stimulus leads to motion sickness
      habituation indicative of the existence of central processes to counteract the
      disturbing properties of the imposed motion. In the present study, we attempt to
      investigate whether NMDA and GABA(A) receptors in rat caudal vestibular nucleus
      neurons are involved in motion sickness habituation induced by repeated Ferris
      wheel like rotation in daily session (2h/d). We showed that defecation response
      increased and spontaneous locomotion decreased within 4 sessions (sickness
      phase). They recovered back to the control level after 7 sessions (habituation
      phase). Western blot analysis found that NMDA receptor signal molecules:
      calmodulin protein kinase II and cAMP response element-binding protein (CREB)
      were both activated during sickness phase, while a prolonged CREB activation was
      also observed during habituation phase. Real-time quantitative PCR revealed an
      increase in c-fos and a decrease in Arc mRNA level during sickness phase. We also
      found an increase in GABA(A) receptor alpha1 subunit (GABA(A) alpha1) protein
      level in this stage. These results suggested that altered NMDA receptor signaling
      and GABA(A) receptor expression level in caudal vestibular nucleus were
      associated with motion sickness habituation. Furthermore, immunofluorescence and
      confocal laser scanning microscopy showed that the number of GABA(A) alpha1
      immunolabeled neurons in caudal vestibular nucleus increased while the number of
      GABA(A) alpha1/Arc double labeled neurons and the average amount of Arc particle
      in soma of these neurons decreased during sickness phase. It suggested that
      GABA(A) receptor level might be negatively regulated by Arc protein in caudal
      vestibular nucleus neurons.

PMID- 22608071
TI  - Effects of acute hypoxia/acidosis on intracellular pH in differentiating neural
      progenitor cells.
AB  - The response of differentiating mouse neural progenitor cells, migrating out from
      neurospheres, to conditions simulating ischemia (hypoxia and extracellular or
      intracellular acidosis) was studied. We show here, by using BCECF and single cell
      imaging to monitor intracellular pH (pH(i)), that two main populations can be
      distinguished by exposing migrating neural progenitor cells to low extracellular
      pH or by performing an acidifying ammonium prepulse. The cells dominating at the
      periphery of the neurosphere culture, which were positive for neuron specific
      markers MAP-2, calbindin and NeuN had lower initial resting pH(i) and could also
      easily be further acidified by lowering the extracellular pH. Moreover, in this
      population, a more profound acidification was seen when the cells were acidified
      using the ammonium prepulse technique. However, when the cell population was
      exposed to depolarizing potassium concentrations no alterations in pH(i) took
      place in this population. In contrast, depolarization caused an increase in pH(i)
      (by 0.5 pH units) in the cell population closer to the neurosphere body, which
      region was positive for the radial cell marker (GLAST). This cell population,
      having higher resting pH(i) (pH 6.9-7.1) also responded to acute hypoxia. During
      hypoxic treatment the resting pH(i) decreased by 0.1 pH units and recovered
      rapidly after reoxygenation. Our results show that migrating neural progenitor
      cells are highly sensitive to extracellular acidosis and that irreversible damage
      becomes evident at pH 6.2. Moreover, our results show that a response to acidosis
      clearly distinguishes two individual cell populations probably representing
      neuronal and radial cells.

PMID- 22608070
TI  - Rodent models of TDP-43: recent advances.
AB  - Recently, missense mutations in the gene TARDBP encoding TDP-43 have been linked
      to familial ALS. The discovery of genes encoding these RNA binding proteins, such
      as TDP-43 and FUS/TLS, raised the notion that altered RNA metabolism is a major
      factor underlying the pathogenesis of ALS. To begin to unravel how mutations in
      TDP-43 cause dysfunction and death of motor neurons, investigators have employed
      both gain- and loss-of-function studies in rodent model systems. Here, we will
      summarize major findings from the initial sets of TDP-43 transgenic and knockout
      rodent models, identify their limitations, and point to future directions toward
      clarification of disease mechanism(s) and testing of therapeutic strategies that
      ultimately may lead to novel therapy for this devastating disease. This article
      is part of a Special Issue entitled RNA-Binding Proteins.

PMID- 22608072
TI  - Dorsal horn antinociception mediated by the paraventricular hypothalamic nucleus
      and locus coeruleous: a comparative study.
AB  - The noradrenergic descending projection originating in the locus coeruleous (LC),
      as well as the oxytocinergic descending projection originating in the
      paraventricular hypothalamic nucleus (PVN), plays a pivotal role in nociception.
      The mechanisms used by these two systems to modulate synaptic nociceptive
      transmission in the dorsal horn have been well studied independently. However,
      little is known about interactions between them. Here, it is shown that both PVN
      and LC electric stimulation inhibit A-delta, C-fiber, and postdischarge
      nociceptive neuronal responses in the same dorsal horn wide dynamic range
      neurons. Moreover, simultaneous stimulation of both the PVN and LC produces
      synergic inhibitory effects. In addition, LC electrolytic lesion or intrathecal
      administration of the alpha-2-adrenoceptor antagonist yohimbine (YOH) blocks the
      inhibitory effect produced by PVN stimulation in A-delta and the postdischarge,
      without affecting the inhibition of C-fiber responses. The results suggest that
      the PVN could inhibit dorsal horn nociceptive responses directly or indirectly by
      modulating the LC descending noradrenergic system.

PMID- 22608073
TI  - Distinct developmental patterns in the expression of transient, persistent, and
      resurgent Na+ currents in entorhinal cortex layer-II neurons.
AB  - Sub- and near-threshold voltage-dependent Na+ currents (VDSCs) are of major
      importance in determining the electrical properties of medial entorhinal cortex
      (mEC) layer-II neurons. Developmental changes in the ability of mEC layer-II
      stellate cells (SCs) to generate Na+ -dependent, subthreshold electrical events
      have been reported between P14 and P18. In this study we examined the
      modifications occurring in the various components of VDSCs during postnatal
      development of mEC SCs. The transient, resurgent, and persistent Na+ currents
      (I(NaT), I(NaR), and I(NaP), respectively) showed distinct patterns of
      developmental expression in the time window considered (P5 to P24-27). All three
      currents prominently and steeply increased in absolute amplitude and conductance
      from P5 to at least P16. However, capacitive charge accumulation, an index of
      membrane surface area, also markedly increased in the same time window, and in
      the case of I(NaT) the specific conductance per unit of accumulated capacitive
      charge remained relatively constant. By contrast, specific I(NaR) and I(NaP)
      conductances showed a significant tendency to increase, especially from P5 to
      P18. Neither I(NaR) nor I(NaP) represented a constant fraction of the total Na+
      current at all developmental ages. Indeed, detectable levels of I(NaR) and I(NaP)
      were present in only ~20% and ~70%, respectively, of the cells on P5, and were
      observed in all cells only from P10 onwards. Moreover, the average I(NaR)-to
      I(NaT) conductance ratio increased steadily from ~0.004 (P5) up to a plateau
      level of ~0.05 (P22+), whereas the I(NaP)-to-I(NaT) conductance ratio increased
      only from ~0.009 on P5 to ~0.02 on P22+. The relative increase in conductance
      ratio from P5 to P22 was significantly greater for I(NaR) than for I(NaP),
      indicating that I(NaR) expression starts later than that of I(NaP). These
      findings show that in mEC layer-II SCs the single functional components of the
      VDSC are regulated differentially from each other as far as their developmental
      expression is concerned.

PMID- 22608074
TI  - Analgesic effect of magnetic stimulation on paclitaxel-induced peripheral
      neuropathic pain in mice.
AB  - Peripheral neuropathies are common side effects of chemotherapeutic drugs,
      including taxanes, platinum-based drugs, vinca alkaloids, and thalidomide. The
      most common symptoms are numbness, tingling and/or burning pain in a stocking
      glove distribution. Severe peripheral neuropathies result in dose reductions, a
      change in chemotherapy regimen, or early cessation of chemotherapy. There are no
      proven interventions to prevent or treat chemotherapy-induced peripheral
      neuropathy. We designed and built a unique magnetic stimulator to clarify the
      effects of magnetic stimulation in the mouse paclitaxel-induced peripheral
      neuropathic pain model. Magnetic stimulation significantly reversed paclitaxel
      induced mechanical hyperalgesia. The analgesic efficacy of magnetic stimulation
      was inhibited by naloxone, a MU opioid receptor antagonist. These findings
      indicate that the analgesic effect of magnetic stimulation is likely to be
      mediated by the endogenous opioid system. Furthermore, a combination of magnetic
      stimulation and pregabalin, a Ca(2+) channel blocker, induced a potent
      combinational analgesic effect, suggesting that analgesic drug dose reduction
      might be possible. These findings indicate that there is a potential therapeutic
      utility for magnetic stimulation in pain relief.

PMID- 22608075
TI  - Combined transcranial magnetic stimulation and electroencephalography: its past,
      present and future.
AB  - Transcranial magnetic stimulation (TMS) is used to index several
      neurophysiological processes including excitability, inhibition and plasticity.
      However, these measures are conventionally limited to the motor cortex and
      recorded from peripheral muscles. This represents a significant limitation when
      non-motor neurophysiological processes are of primary interest. In the last
      several years, TMS has been combined with electroencephalography (EEG) to derive
      such measures directly from the cortex. Initial studies demonstrated that
      meaningful recordings could be derived without being substantially affected by
      TMS stimulus artifact due to advancements in EEG amplifier technology.
      Subsequently, TMS measures of cortical excitability were reliably recorded and
      found to be related with more conventional TMS electromyography recordings of
      excitability in the cortex. More recently, other key neurophysiological indices
      including cortical inhibition and interhemispheric connectivity have also been
      reported. In this article, such findings will be reviewed and their importance
      discussed vis a vis healthy and disease states. We will conclude by highlighting
      the limitations of this work and discuss their potential future applications as a
      biomarker of disease states.

PMID- 22608076
TI  - The conditioned medium of murine and human adipose-derived stem cells exerts
      neuroprotective effects against experimental stroke model.
AB  - This study investigated the possible ameliorative effects of adipose-derived stem
      cells-conditioned medium (ASC-CM) on experimental ischemic stroke. In vivo
      ischemic stroke was induced in mice after 2h of middle cerebral artery occlusion
      (MCAO) followed by 22 h reperfusion. Culture of SH-SY5Y human neuroblastoma cells
      with 100 MUM glutamate for 24h was used as an in vitro neuronal apoptosis model.
      Intracerebroventricular (i.c.v.) administration of 30- and 100-fold concentrated
      murine ASC-CM 1h prior to MCAO resulted in a dose-dependent reduction in the
      infarct volume and the brain swelling. The administration of murine ASC-CM
      immediately after MCAO was also effective, but administration 2h after MCAO was
      not. Neuroprotective effects of murine ASC-CM were also confirmed in an in vitro
      model. Pretreatment with 100-fold concentrated murine ASC-CM at 10% of the total
      culture volume significantly reduced glutamate-induced excitotoxicity in the SH
      SY5Y cells. Similar reduction in the MCAO-induced infarction volume was seen
      following i.c.v. administration of 100-fold concentrated human ASC-CM or murine
      ASC-CM. In conclusion, ASC-CM appears to exert ameliorative effects on
      experimental ischemic stroke i?n both in vivo and in vitro models. These findings
      suggest the feasibility of ASC-CM administration as a therapy for acute stage
      stroke.

PMID- 22608077
TI  - Muscarinic receptor activation disrupts hippocampal sharp wave-ripples.
AB  - Cholinergic muscarinic innervations to the hippocampus play a role in learning
      and memory. Here we report that pharmacological activation of muscarinic
      receptors eliminates sharp wave-ripple events in the mouse hippocampal CA1 region
      in vivo and in vitro. This effect was associated with a decorrelation of
      excitatory synaptic inputs and a net increase in inhibitory conductances in
      pyramidal neurons. Multineuron calcium imaging revealed that muscarinic
      activation altered the spatiotemporal pattern of network activities. Thus,
      cholinergic input is likely to contribute to a neuromodulatory switch of
      hippocampal network states, as proposed in the "two-stage" model of learning
      processes.

PMID- 22608078
TI  - Enhancement of phytosterols, taraxasterol and induction of extracellular
      pathogenesis-related proteins in cell cultures of Solanum lycopersicum cv Micro
      Tom elicited with cyclodextrins and methyl jasmonate.
AB  - Suspension-cultured cells of Solanum lycopersicum cv Micro-Tom were used to
      evaluate the effect of methyl jasmonate and cyclodextrins, separately or in
      combination, on the induction of defense responses. An extracellular accumulation
      of two sterols (isofucosterol and beta-sitosterol) and taraxasterol, a common
      tomato fruit cuticular triterpene, were observed. Their levels were higher in
      Micro-Tom tomato suspension cultured cells elicited with cyclodextrins than in
      control and methyl jasmonate-treated cells. Also, their accumulation profiles
      during the cell growth phase were markedly different. The most striking feature
      in response to cyclodextrin treatments was the observed enhancement of
      taraxasterol accumulation. Likewise, the exogenous application of methyl
      jasmonate and cyclodextrins induced the accumulation of pathogenesis-related
      proteins. Analysis of the extracellular proteome showed the presence of amino
      acid sequences homologous to pathogenesis-related 1 and 5 proteins, a cationic
      peroxidase and a biotic cell death-associated protein, which suggests that methyl
      jasmonate and cyclodextrins could play a role in mediating defense-related gene
      product expression in S. lycopersicum cv Micro-Tom.

PMID- 22608079
TI  - Ascorbic acid metabolism during bilberry (Vaccinium myrtillus L.) fruit
      development.
AB  - Bilberry (Vaccinium myrtillus L.) possesses a high antioxidant capacity in
      berries due to the presence of anthocyanins and ascorbic acid (AsA). Accumulation
      of AsA and the expression of the genes encoding the enzymes of the main AsA
      biosynthetic route and of the ascorbate-glutathione cycle, as well as the
      activities of the enzymes involved in AsA oxidation and recycling were
      investigated for the first time during the development and ripening of bilberry
      fruit. The results showed that the AsA level remained relatively stable during
      fruit maturation. The expression of the genes encoding the key enzymes in the AsA
      main biosynthetic route showed consistent trends with each other as well as with
      AsA levels, especially during the first stages of fruit ripening. The expression
      of genes and activities of the enzyme involved in the AsA oxidation and recycling
      route showed more prominent developmental stage-dependent changes during the
      ripening process. Different patterns of activity were found among the studied
      enzymes and the results were, for some enzymes, in accordance with AsA levels. In
      fully ripe berries, both AsA content and gene expression were significantly
      higher in skin than in pulp.

PMID- 22608080
TI  - Tomato fruit development in the auxin-resistant dgt mutant is induced by
      pollination but not by auxin treatment.
AB  - In tomato (Solanum lycopersicum Mill.), auxin is believed to play a pivotal role
      in controlling fruit-set and early ovary growth. In this paper we investigated
      the effect of the reduced auxin sensitivity exhibited by the diageotropica (dgt)
      tomato mutant on ovary growth during early stage of fruit development. Here we
      show that in hand-pollinated ovaries fruit-set was not affected by the dgt lesion
      while fruit growth was reduced. This reduction was associated with a smaller cell
      size of mesocarp cells, with a lower mean C values and with a lower gene
      expression of the expansin gene LeExp2. When a synthetic auxin (4-CPA,
      chlorophenoxyacetic acid) was applied to the flowers of wild type plants,
      parthenocarpic ovary growth was induced. On the contrary, auxin application to
      the flowers of dgt plants failed to induce parthenocarpy. Hand-pollinated ovaries
      of dgt contained higher levels of IAA compared to wild type and this was not
      associated with high transcript levels of genes encoding a key regulatory enzyme
      of IAA biosynthesis (ToFZYs) but with lower expression levels of GH3, a gene
      involved in the conjugation of IAA to amino acids. The expression of diverse
      Aux/IAA genes and SAUR (small auxin up-regulated RNA) was also altered in the dgt
      ovaries. The dgt lesion does not seem to affect specific Aux/IAA genes in terms
      of transcript occurrence but rather in terms of relative levels of expression.
      Transcript levels of Aux/IAA genes were up regulated in auxin-treated ovaries of
      wild-type but not in dgt. Together, our results suggest that dgt ovary cells are
      not able to sense and/or transduce the external auxin signal, whereas pollinated
      dgt ovary cells are able to detect the IAA present in fertilized ovules promoting
      fruit development.

PMID- 22608081
TI  - Mechanisms and anatomy of unilateral extinction after brain injury.
AB  - Unilateral extinction is a common consequence of unilateral brain injury in which
      individuals fail to detect a contralesional target when presented together with a
      competing ipsilesional target. Here we review the literature on the different
      mechanisms and anatomy hypothesized to underlie unilateral extinction. We argue
      that extinction, which reflects a specific deficit in the simultaneous processing
      of multiple briefly presented targets, should be distinguished from the failure
      to actively explore and serially detect targets amongst distractors in
      contralesional space commonly known as spatial neglect. While contralesional
      sensory defects can be correlated with extinction, these sensory impairments
      alone are usually not sufficient to explain the deficit. Prototypical extinction
      is instead best seen as the result of a pathologically biased competition between
      multiple target representations for pathologically limited attentional resources.
      The temporo-parietal junction (TPJ) is a critical site in many of the lesions
      that provoke extinction. Additionally, the intraparietal sulcus (IPS) may play a
      role in modulation of competitive interactions between multiple target
      representations.

PMID- 22608082
TI  - Allocentric neglect strongly associated with egocentric neglect.
AB  - Following brain injury, many patients experience egocentric spatial neglect,
      where they fail to respond to stimuli on the contralesional side of their body.
      On the other hand, allocentric, object-based neglect refers to the symptom of
      ignoring the contralesional side of objects, regardless of the objects'
      egocentric position. There is an established tradition for considering these two
      phenomena as both behaviorally and anatomically dissociable. However, several
      studies and some theoretical work have suggested that these rather reflect two
      aspects of a unitary underlying disorder. Furthermore, in a recent large study
      Yue et al. [Archives of Physical Medicine and Rehabilitation 93 (2012) 156]
      reported that acute allocentric neglect is only observed in cases where
      substantial egocentric neglect is also present. In a new sample of right
      hemisphere stroke patients, we attempted to control for potential confounds by
      using a novel continuous measure for allocentric neglect (in addition to a
      recently developed continuous measure for egocentric neglect). Our findings
      suggest a strong association between egocentric and allocentric neglect.
      Consistent with the work of Yue et al. (2012), we found allocentric behavioral
      deficits only in conjunction with egocentric deficits as well as a large
      corresponding overlap for the anatomical regions associated with egocentric and
      with allocentric neglect. We discuss how different anatomical and behavioral
      findings can be explained in a unified physiologically plausible framework,
      whereby allocentric and egocentric effects interact.

PMID- 22608083
TI  - The life history of 21 breast cancers.
AB  - Cancer evolves dynamically as clonal expansions supersede one another driven by
      shifting selective pressures, mutational processes, and disrupted cancer genes.
      These processes mark the genome, such that a cancer's life history is encrypted
      in the somatic mutations present. We developed algorithms to decipher this
      narrative and applied them to 21 breast cancers. Mutational processes evolve
      across a cancer's lifespan, with many emerging late but contributing extensive
      genetic variation. Subclonal diversification is prominent, and most mutations are
      found in just a fraction of tumor cells. Every tumor has a dominant subclonal
      lineage, representing more than 50% of tumor cells. Minimal expansion of these
      subclones occurs until many hundreds to thousands of mutations have accumulated,
      implying the existence of long-lived, quiescent cell lineages capable of
      substantial proliferation upon acquisition of enabling genomic changes. Expansion
      of the dominant subclone to an appreciable mass may therefore represent the final
      rate-limiting step in a breast cancer's development, triggering diagnosis.

PMID- 22608084
TI  - Mutational processes molding the genomes of 21 breast cancers.
AB  - All cancers carry somatic mutations. The patterns of mutation in cancer genomes
      reflect the DNA damage and repair processes to which cancer cells and their
      precursors have been exposed. To explore these mechanisms further, we generated
      catalogs of somatic mutation from 21 breast cancers and applied mathematical
      methods to extract mutational signatures of the underlying processes. Multiple
      distinct single- and double-nucleotide substitution signatures were discernible.
      Cancers with BRCA1 or BRCA2 mutations exhibited a characteristic combination of
      substitution mutation signatures and a distinctive profile of deletions. Complex
      relationships between somatic mutation prevalence and transcription were
      detected. A remarkable phenomenon of localized hypermutation, termed "kataegis,"
      was observed. Regions of kataegis differed between cancers but usually
      colocalized with somatic rearrangements. Base substitutions in these regions were
      almost exclusively of cytosine at TpC dinucleotides. The mechanisms underlying
      most of these mutational signatures are unknown. However, a role for the APOBEC
      family of cytidine deaminases is proposed.

PMID- 22608085
TI  - Comprehensive analysis of mRNA methylation reveals enrichment in 3' UTRs and near
      stop codons.
AB  - Methylation of the N(6) position of adenosine (m(6)A) is a posttranscriptional
      modification of RNA with poorly understood prevalence and physiological
      relevance. The recent discovery that FTO, an obesity risk gene, encodes an m(6)A
      demethylase implicates m(6)A as an important regulator of physiological
      processes. Here, we present a method for transcriptome-wide m(6)A localization,
      which combines m(6)A-specific methylated RNA immunoprecipitation with next
      generation sequencing (MeRIP-Seq). We use this method to identify mRNAs of 7,676
      mammalian genes that contain m(6)A, indicating that m(6)A is a common base
      modification of mRNA. The m(6)A modification exhibits tissue-specific regulation
      and is markedly increased throughout brain development. We find that m(6)A sites
      are enriched near stop codons and in 3' UTRs, and we uncover an association
      between m(6)A residues and microRNA-binding sites within 3' UTRs. These findings
      provide a resource for identifying transcripts that are substrates for adenosine
      methylation and reveal insights into the epigenetic regulation of the mammalian
      transcriptome.

PMID- 22608087
TI  - Trapping of Rift Valley Fever (RVF) vectors using light emitting diode (LED) CDC
      traps in two arboviral disease hot spots in Kenya.
AB  - BACKGROUND: Mosquitoes' response to artificial lights including color has been
      exploited in trap designs for improved sampling of mosquito vectors. Earlier
      studies suggest that mosquitoes are attracted to specific wavelengths of light
      and thus the need to refine techniques to increase mosquito captures following
      the development of super-bright light-emitting diodes (LEDs) which emit narrow
      wavelengths of light or very specific colors. Therefore, we investigated if LEDs
      can be effective substitutes for incandescent lamps used in CDC light traps for
      mosquito surveillance, and if so, determine the best color for attraction of
      important Rift Valley Fever (RFV) vectors. METHODS: The efficiency of selected
      colored LED CDC light traps (red, green, blue, violet, combination of blue-green
      red (BGR)) to sample RVF vectors was evaluated relative to incandescent light (as
      control) in a CDC light trap in two RVF hotspots (Marigat and Ijara districts) in
      Kenya. In field experiments, traps were baited with dry ice and captures
      evaluated for Aedes tricholabis, Ae. mcintoshi, Ae. ochraceus, Mansonia
      uniformis, Mn. africana and Culex pipiens, following Latin square design with
      days as replicates. Daily mosquito counts per treatment were analyzed using a
      generalized linear model with Negative Binomial error structure and log link
      using R. The incidence rate ratios (IRR) that mosquito species chose other
      treatments instead of the control, were estimated. RESULTS: Seasonal preference
      of Ae.mcintoshi and Ae. ochraceus at Ijara was evident with a bias towards BGR
      and blue traps respectively in one trapping period but this pattern waned during
      another period at same site with significantly low numbers recorded in all
      colored traps except blue relative to the control. Overall results showed that
      higher captures of all species were recorded in control traps compared to the
      other LED traps (IRR < 1) although only significantly different from red and
      violet. CONCLUSION: Based on our trapping design and color, none of the LEDs
      outcompeted the standard incandescent light. The data however provides
      preliminary evidence that a preference might exist for some of these mosquito
      species based on observed differential attraction to these light colors requiring
      future studies to compare reflected versus transmitted light and the
      incorporation of colored light of varying intensities.

PMID- 22608088
TI  - Society for complexity in acute illness and sepsis.

PMID- 22608086
TI  - Base-resolution analysis of 5-hydroxymethylcytosine in the mammalian genome.
AB  - The study of 5-hydroxylmethylcytosines (5hmC) has been hampered by the lack of a
      method to map it at single-base resolution on a genome-wide scale. Affinity
      purification-based methods cannot precisely locate 5hmC nor accurately determine
      its relative abundance at each modified site. We here present a genome-wide
      approach, Tet-assisted bisulfite sequencing (TAB-Seq), that when combined with
      traditional bisulfite sequencing can be used for mapping 5hmC at base resolution
      and quantifying the relative abundance of 5hmC as well as 5mC. Application of
      this method to embryonic stem cells not only confirms widespread distribution of
      5hmC in the mammalian genome but also reveals sequence bias and strand asymmetry
      at 5hmC sites. We observe high levels of 5hmC and reciprocally low levels of 5mC
      near but not on transcription factor-binding sites. Additionally, the relative
      abundance of 5hmC varies significantly among distinct functional sequence
      elements, suggesting different mechanisms for 5hmC deposition and maintenance.

PMID- 22608089
TI  - What the situation of neonatal death in the NICUs of Taiwan Is.

PMID- 22608091
TI  - Comments on "Impaired renal function is associated with greater urinary strong
      ion differences in critically ill patients with metabolic acidosis".

PMID- 22608092
TI  - Introduction for the 10th International Conference on Complexity in Acute Illness
      abstracts.

PMID- 22608093
TI  - Deep-brain-stimulation does not impair deglutition in Parkinson's disease.
AB  - OBJECTIVE: A large proportion of patients with Parkinson's disease develop
      dysphagia during the course of the disease. Dysphagia in Parkinson's disease
      affects different phases of deglutition, has a strong impact on quality of life
      and may cause severe complications, i.e., aspirational pneumonia. So far, little
      is known on how deep-brain-stimulation of the subthalamic nucleus influences
      deglutition in PD. METHODS: Videofluoroscopic swallowing studies on 18 patients
      with Parkinson's disease, which had been performed preoperatively, and
      postoperatively with deep-brain-stimulation-on and deep-brain-stimulation-off,
      were analyzed retrospectively. The patients were examined in each condition with
      three consistencies (viscous, fluid and solid). The 'New Zealand index for
      multidisciplinary evaluation of swallowing (NZIMES) Subscale One' for qualitative
      and 'Logemann-MBS-Parameters' for quantitative evaluation were assessed. RESULTS:
      Preoperatively, none of the patients presented with clinically relevant signs of
      dysphagia. While postoperatively, the mean daily levodopa equivalent dosage was
      reduced by 50% and deep-brain-stimulation led to a 50% improvement in motor
      symptoms measured by the UPDRS III, no clinically relevant influence of deep
      brain-stimulation-on swallowing was observed using qualitative parameters
      (NZIMES). However quantitative parameters (Logemann scale) found significant
      changes of pharyngeal parameters with deep-brain-stimulation-on as compared to
      preoperative condition and deep-brain-stimulation-off mostly with fluid
      consistency. CONCLUSION: In Parkinson patients without dysphagia deep-brain
      stimulation of the subthalamic nucleus modulates the pharyngeal deglutition phase
      but has no clinically relevant influence on deglutition. Further studies are
      needed to test if deep-brain-stimulation is a therapeutic option for patients
      with swallowing disorders.

PMID- 22608094
TI  - Isolation and culture of pig tonsil lymphocytes.
AB  - Tonsils are secondary lymphoid organs that play an important role in host
      defense. The aim of our study was to develop reliable procedures for isolation
      and culture of pig tonsil cells, and to validate their possible use in functional
      immunoassays. Using our isolation procedure, we recovered on average 238.7 +/-
      107.1 * 10(6) cells per tonsil couple with a mean vitality of 89.8 +/- 2.7%.
      These values significantly decreased 8 months after freezing at -80 degrees C
      along with the subsequent spontaneous release of both IgA and IgG in culture.
      These results suggest to use pig tonsil cells within 2 months from thawing to
      maintain suitable conditions in terms of recovery, vitality and release of
      antibody in vitro. Tonsil mononuclear cells also showed the ability to secrete
      antimicrobial peptides and to respond in vitro to immunological stimuli. On the
      whole, our study has defined operating conditions for tonsil processing, control
      of bacterial contaminations, time limits of storage at -80 degrees C, as well as
      for evaluating polyclonal Ig production in vitro. Such procedures are likely to
      be of some importance in studies on regional immunity and in the development of
      large animal models for biomedical sciences.

PMID- 22608095
TI  - DNA hypomethylation of the COX-2 gene promoter is associated with up-regulation
      of its mRNA expression in eutopic endometrium of endometriosis.
AB  - BACKGROUND: Accumulated evidence reveals that cyclooxygenase-2 (COX-2) was
      overexpressed in eutopic endometrium of endometriosis, which may play a critical
      role in the pathogenesis of endometriosis. However, few studies have been
      performed to explore the molecular mechanisms underlying the abnormal high
      expression of COX-2 in endometriosis. Considering the fact that a number of
      recent studies have shown DNA methylation affecting some genes in endometriosis,
      the present study was therefore aimed to determine whether the observed high
      expression COX-2 in endometriosis is caused by the hypomethylation of CpG island
      within the promoter of this gene. METHODS: The endometrial tissues were collected
      from 60 women with endometriosis (endometriosis group) and 20 women without
      endometriosis (control group). The methylation status of COX-2 was examined by
      methylation specific PCR. Quantitative real-time RT-PCR was performed to measure
      COX-2 mRNA level in endometrial tissues. RESULTS: The frequency of promoter
      hypermethylation of COX-2 was lower in eutopic endometrium of the endometriosis
      group (41.7%) than that in the control group (75.0%), P < 0.05. COX-2 mRNA level
      in the eutopic endometrium of the endometriosis group was 2.61-fold higher than
      that in the control group (P < 0.01). COX-2 mRNA level in unmethylated
      endometrium of the endometriosis group or the control group was 2.39-fold and
      2.66-fold, respectively, higher than that in the methylated endometrium of the
      same group (P < 0.01). CONCLUSIONS: The hypomethylation within the promoter of
      COX-2 may be responsible for the elevated gene expression in eutopic endometrium
      of endometriosis.

PMID- 22608096
TI  - A reliable and rapid tool for plasma quantification of 18 psychotropic drugs by
      ESI tandem mass spectrometry.
AB  - A simple liquid chromatographic tandem mass spectrometry (LC-MS/MS) method has
      been developed for simultaneous analysis of 17 basic and one acid psychotropic
      drugs in human plasma. The method relies on a protein precipitation step for
      sample preparation and offers high sensitivity, wide linearity without
      interferences from endogenous matrix components. Chromatography was run on a
      reversed-phase column with an acetonitrile-H2O mixture. The quantification of
      target compounds was performed in multiple reaction monitoring (MRM) and by
      switching the ionization polarity within the analytical run. A further
      sensitivity increase was obtained by implementing the functionality "scheduled
      multiple reaction monitoring" (sMRM) offered by the recent version of the
      software package managing the instrument. The overall injection interval was less
      than 5.5 min. Regression coefficients of the calibration curves and limits of
      quantification (LOQ) showed a good coverage of over-therapeutic, therapeutic and
      sub-therapeutic ranges. Recovery rates, measured as percentage of recovery of
      spiked plasma samples, were >= 94%. Precision and accuracy data have been
      satisfactory for a therapeutic drug monitoring (TDM) service as for managing
      plasma samples from patients receiving psycho-pharmacological treatment.

PMID- 22608097
TI  - Fast and sample cleanup-free measurement of nicotine and cotinine by stable
      isotope dilution ultra-performance liquid chromatography-tandem mass
      spectrometry.
AB  - We developed a stable isotope dilution ultra-performance liquid chromatography
      electrospray ionization tandem mass spectrometry assay to measure nicotine and
      cotinine, the major oxidative and pharmacologically less active metabolite of
      nicotine, in human urine. A simple dilution step was used as sample preparation
      and the measurement of nicotine and cotinine was performed during a 1.5-min run
      time using nicotine-D4 and cotinine-D4 as internal standards. Multiple
      calibration curves for the analysis of both nicotine and cotinine exhibited a
      consistent excellent linearity and reproducibility in the range of 5-35,000 MUg/L
      (r>0.999). Limits of Detection were 0.7 MUg/L for nicotine and 0.4 MUg/L for
      cotinine, and Lower Limits of Quantification were 1.7 MUg/L for nicotine and 1.1
      MUg/L for cotinine. The intraassay coefficients of variation (CVs) for nicotine
      and cotinine were <4% and <2%, respectively, the interassay CVs were <6% for
      nicotine and <4% for cotinine. The inaccuracy was <6% for both substances. The
      mean recovery was 103.2% (range 96.8-105.1%) for nicotine and 97.4% (range 94.3
      99.2%) for cotinine. A method comparison showed that the values of nicotine
      metabolites in human urine samples (n=98) measured by a commercially available
      chemiluminescent immunoassay tested on analyzer IMMULITE 2000 were much higher
      than the cotinine concentration in the same urine samples measured by our UPLC
      MS/MS assay. The Passing-Bablok regression line was: immunoassay=4.62 (UPLC
      MS/MS)+3.64 [MUg/L]; r=0.75. This robust, sensitive and interference-free UPLC
      MS/MS assay permits rapid and accurate determination of nicotine and cotinine in
      human urine.

PMID- 22608098
TI  - Quantification of tetramethyl-terephthalic acid in rat liver, spleen and urine
      matrices by liquid-liquid phase extraction and HPLC-photodiode array detection.
AB  - Tetramethyl-terephthalate (TMT) is the constitutive linker of the flexible porous
      iron(III) carboxylate Metal Organic Framework (MOF) MIL-88B_4CH3 based drug
      nanocarrier (MIL stands for Material from Institut Lavoisier). A method for the
      determination of the concentration of tetramethyl-terephthalic acid has been
      developed in different biological rat matrices (liver, spleen and urine) using a
      liquid-liquid phase extraction and high-performance liquid chromatography (HPLC)
      coupled to photodiode array detection with 4-aminosalicylic acid as internal
      standard. The extraction conditions of TMT have been varied from urine to tissue
      depending on the complexity of the biological matrices. The chromatographic
      separation was performed with a gradient elution. In all matrices, the limits of
      detection and quantification of TMT was 0.01 and 0.05 MUg ml-1, respectively. The
      recovery of the TMT reached 86, 89 and 97% for urine, spleen and liver tissues,
      respectively. The linearity of the calibration curves in urine and tissues was
      satisfactory in all cases as evidenced by correlation coefficients >0.990. The
      within-day and between-day precisions were <15% (n=6) and the accuracy ranged in
      all cases between 86 and 103%. This method has finally allowed the quantification
      of TMT in rat urine and in tissue samples of rats administered intravenously with
      iron(III) tetramethyltherepthalate MIL-88B_4CH3 nanoparticles.

PMID- 22608099
TI  - Population dynamics of filamentous bacteria in Danish wastewater treatment plants
      with nutrient removal.
AB  - Bulking and foaming are two frequently occurring operational problems in
      activated sludge wastewater treatment plants, and these problems are mainly
      associated with excessive growth of filamentous bacteria. In this study, a
      comprehensive investigation of the identity and population dynamics of
      filamentous bacteria in 28 Danish municipal treatment plants with nutrient
      removal has been carried out over three years. Fluorescence in situ hybridization
      was applied to quantify more than twenty probe-defined populations of filamentous
      bacteria that in total constituted a large fraction of the entire microbial
      community, on average 24%. Despite the majority being present within the flocs,
      they occasionally caused settling problems in most of the plants. A low diversity
      of probe-defined filamentous bacteria was found in the plants with Microthrix and
      various species belonging to phylum Chloroflexi (e.g., type 0803 and type 0092)
      as the most abundant. Few other filamentous probe-defined species were found
      revealing a large similarity between the filamentous populations in the plants
      investigated. The composition of filamentous populations was stable in each plant
      with only minor changes in relative abundances observed during the three-year
      study period. The relative composition of the different species was unique to
      each plant giving a characteristic "fingerprint". Comprehensive statistical
      analyses of the presence and abundance of the filamentous organisms did not
      reveal many correlations with a particular plant design or process parameter.

PMID- 22608100
TI  - Virulence potential of fusogenic orthoreoviruses.
AB  - Several severe respiratory virus infections that have emerged during the past
      decade originated in animals, including bats. In Indonesia, exposure to bats has
      been associated with increased risk of acquiring orthoreovirus infection.
      Although orthoreovirus infections are mild and self-limiting, we explored their
      potential for evolution into a more virulent form. We used conventional virus
      culture, electron microscopy, and molecular sequencing to isolate and identify
      orthoreoviruses from 3 patients in whom respiratory tract infection developed
      after travel to Indonesia. Virus characterization by plaque-reduction
      neutralization testing showed antigenic similarity, but sequencing of the small
      segment genes suggested virus reassortment, which could lead to increased
      virulence. Bats as a reservoir might contribute to virus evolution and genetic
      diversity, giving orthoreoviruses the potential to become more virulent.
      Evolution of this virus should be closely monitored so that prevention and
      control measures can be taken should it become more virulent.

PMID- 22608101
TI  - Characterization of two putative mechanosensitive channel proteins of
      Campylobacter jejuni involved in protection against osmotic downshock.
AB  - Acute hypotonic stress becomes a threat to the survival of bacteria in the
      environment. Mechanosensitive channels play an essential role in the maintenance
      of bacterial cell integrity during hypoosmotic shock. A database search suggested
      that Campylobacter jejuni, a major worldwide cause of bacterial gastroenteritis
      in humans, possesses two putative mechanosensitive channels, designated Cjj0263
      and Cjj1025, in C. jejuni strain 81-176. Osmotic downshock experiments
      demonstrated that a mutant lacking Cjj0263 showed a severe defect in survival of
      hypoosmotic shock, while a mutant lacking Cjj1025 exhibited the same survival
      capacity as the wild type. We further examined the colonization ability of each
      mutant using the one-day old chick model. Cjj0263 or Cjj1025 mutants were able to
      colonize chick ceca at the same level as the wild type, but a Cjj0263 Cjj1025
      double mutant revealed significantly reduced ability to colonize chick ceca. To
      examine whether C. jejuni that have grown in the digestive tract of chicks are
      protected against acute hypotonic stress, bacteria in ceca were directly exposed
      to water. The wild type was able to survive acute osmotic downshift, but the
      Cjj0263 mutant suffered a substantial loss of viability when subjected to a rapid
      osmotic downshock. Immunoblot analysis suggested that both Cjj0263 and Cjj1025
      were glycosylated via the N-linked protein glycosylation pathway, but glycan
      modification of these proteins was unlikely to have a major effect on their
      function and stability. Our data suggest that Cjj0263, a mechanosensitive
      channel, has a pivotal role in protection against hypoosmotic stress experienced
      during environmental transmission.

PMID- 22608102
TI  - First description of Trueperella (Arcanobacterium) bernardiae of animal origin.
AB  - In the present study a Trueperella (Arcanobacterium) bernardiae strain isolated
      from an anal swab of a three-day-old piglet could be identified phenotypically,
      by matrix-assisted laser desorption ionization-time of flight mass spectrometry
      (MALDI-TOF MS) and genotypically by sequencing the 16S rDNA, the 16S-23S rDNA
      intergenic spacer region (ISR) and by sequencing the superoxide dismutase A
      encoding gene sodA. The present study gives the first information about the
      presence of T. (A.) bernardiae in specimen of animals.

PMID- 22608103
TI  - Early pathogenesis of classical swine fever virus (CSFV) strains in Danish pigs.
AB  - Host-virus interactions play an important role for the clinical outcome of
      classical swine fever virus (CSFV) infections in pigs. Strain virulence, host
      characteristics and environment are all factors that markedly influence disease
      severity. We tested CSFV strains of varying virulence in an experimental set-up,
      reducing the influence of host and environmental factors. Thus, weaner pigs were
      inoculated with one of 4 CSFV strains in order to compare the pathogenesis for a
      3-week-period after infection. CSFV strains selected were 2 new and 2 previously
      characterized. None of these strains had been tested in Danish outbred pigs
      before. Clinical observations grouped the infected pigs into two different
      categories reflecting either non-specific, mainly gastro-intestinal, problems, or
      severe disease including high fever within the first week after inoculation.
      Gross-pathological findings varied between strains, however, lymphoid atrophy and
      growth retardation represented a consistent finding for all 4 strains. Virus
      distribution, viral load and in particular virus persistence differed, but
      supported present practice that recommends lymphoid tissue, most optimal tonsil
      and lymph nodes, as target material to be applied for early laboratory diagnosis.
      The present study demonstrated constraints associated with early detection of
      infections with CSFV strains of low virulence. Since neither clinical symptoms
      nor pathological lesions observed with these strains constituted characteristic
      signs of CSF, the risk of neglecting a CSF suspicion is immediate. Therefore,
      topical information on new outbreaks and continuous enhancement of an efficient
      surveillance system is of great importance to prevent further spread of CSF
      within the pig population.

PMID- 22608104
TI  - Decarboxylation activity of enterococci isolated from rabbit meat and
      staphylococci isolated from trout intestines.
AB  - The aim of the study was to explore production of seven biogenic amines
      (phenylethylamine, histamine, cadaverine, tyramine, putrescine, spermine and/or
      spermidine) by selected staphylococci and enterococci. Thirty three enterococcal
      strains isolated from rabbit meat (Oryctolagus cuniculus f. domesticus) and 21
      staphylococcal strains isolated from intestinal content of trout (Salmo trutta
      morpha fario) were tested. Production of biogenic amines was evaluated after
      cultivation of the tested microorganisms in the de Man, Rogosa and Sharpe Broth
      (enterococci) or in the Brain Heart Infusion Broth (staphylococci). Both the
      above cultivation media were enriched with selected amino acids (histidine,
      tyrosine, arginine, ornithine and lysine; 2g/L each) serving as precursors of
      biogenic amines. After cultivation, levels of the monitored biogenic amines in
      broths were analysed by a high performance liquid chromatography equipped with a
      UV/VIS DAD detector. Among 21 staphylococci, 18 strains produced tyramine or
      cadaverine, 13 strains formed putrescine or phenylethylamine and only one strain
      generated histamine. Two staphylococcal strains produced cadaverine levels above
      1000 mg/L. Among 33 enterococcal strains, 27 formed cadaverine, 18 strains
      produced tyramine, 10 strains generated phenylethylamine, and 2 strains gave
      putrescine. Most of the tyramine producing enterococci generated more than 1000
      mg/L of this biogenic amine. Production of spermine or spermidine by the studied
      strains was not proved.

PMID- 22608105
TI  - Costs and clinical outcomes associated with use of ranolazine for treatment of
      angina.
AB  - BACKGROUND: There are 10 million patients with angina in the United States
      (500,000 new diagnoses annually). Although clinical efficacy of angina treatments
      is understood, total costs of care and clinical outcomes for patients with
      chronic angina in different treatment protocols are unknown. OBJECTIVE: Our
      objective was to estimate total costs of care and revascularization rates for
      patients with poorly controlled angina who added either (1) long-acting nitrates,
      (2) beta blockers or calcium channel blockers, or (3) ranolazine to their
      therapy. STUDY DESIGN: We performed retrospective claims analysis using an index
      event involving change of therapy in which a new antiangina drug was added.
      METHODS: Using a large commercial insurance claims database, 4545 patients with
      angina with an index event (ie, change of antiangina therapy) and 6 months of
      continuous enrollment pre- and postindex event were identified. Using total cost
      of care and revascularization rates, we first compared preindex disease burden,
      medical care use, and total cost of care and components of total cost. We then
      compared unadjusted use and cost of care across treatment groups. Finally, we
      estimated regression models to predict postindex event total costs of care and
      revascularization rates. RESULTS: During the preindex period, the 3 comparison
      groups had similar health measures, medical care use, and total costs of care.
      During the postindex period, ranolazine users had lower revascularization rates
      (9.9%) than comparison patient groups (15.4%-20.4%, both Ps < 0.001). Ranolazine
      users had lower total costs of care ($13,961) than the nitrate group ($18,166,
      30.0% higher; P < 0.001) and the beta blockers/calcium channel blockers group
      ($17,612, 26.6% higher; P = 0.002). CONCLUSIONS: Adding ranolazine to the
      treatment regimen of patients with poorly controlled angina was associated with
      lower rates of revascularization and lower total costs of care than for
      comparable patients, differences both statistically and clinically relevant.

PMID- 22608106
TI  - Long-term effects of adding exenatide to a regimen of metformin and/or
      sulfonylurea in type 2 diabetes: an uncontrolled, open-label trial in Hungary.
AB  - BACKGROUND: Studies of the glucagon-like peptide-1 receptor agonists (GLP-1RAs)
      are needed to determine the durability of metabolic response and tolerability
      associated with long-term treatment. OBJECTIVE: The present study was conducted
      to provide long-term data on glycemic control, weight changes, and tolerability
      of exenatide 10 MUg BID treatment in patients with type 2 diabetes mellitus who
      have failed to achieve glycemic targets with oral antihyperglycemic medication.
      METHODS: In this uncontrolled, open-label trial with treatment up to 156 weeks,
      patients received exenatide 10 MUg BID while continuing treatment with metformin
      and/or a sulfonylurea (SFU). Intent-to-treat (ITT), 52-, 100-, and 132-week
      completer populations were defined. Metabolic changes were analyzed in the
      completer and ITT populations; adverse events (AEs) were summarized in the ITT
      population. Descriptive statistics were used for absolute and change-from
      baseline data. Within-treatment comparisons were conducted using the paired t
      test. RESULTS: Of 155 patients in the ITT population (mean [SD]: age, 59 [9]
      years; 56% female; duration of diabetes, 9.1 [5.9] years; weight, 88.8 [16.5] kg;
      body mass index, 31.9 [4.7] kg/m(2); hemoglobin [Hb] A(1c), 8.7% [1.2%]), 133,
      111, and 103 patients completed 52, 100, and 132 weeks of treatment,
      respectively. In the ITT population, the mean (SE) change in HbA(1c) from
      baseline to week 132 was -1.0% (0.10%) (P < 0.0001). In patients completing 52,
      100, and 132 weeks, HbA(1c) changes from baseline to end point were -1.3%
      (0.10%), -1.0% (0.12%), and -1.0 (0.13%) (P < 0.0001), with 40% of patients
      achieving HbA(1c) <7% at 132 weeks. Patients in the ITT and completer populations
      experienced mean (SE) weight changes of -3.7 (0.39) kg and -3.9 (0.51) kg (P <
      0.0001) at week 132. Improved glycemic control and weight loss occurred in 63% of
      patients in the completer population at week 132. In addition, 38% of completers
      at week 132 achieved HbA(1c) <7% without weight gain. No relationship was found
      between the development of antiexenatide antibodies and change in HbA(1c). The
      most common AEs were gastrointestinal in nature, reported in 46% of patients and
      leading to discontinuation in 7 cases. Serious AEs were reported in 26% of
      patients, and 18% withdrew due to a treatment-emergent AE. Of 24% of patients in
      whom hypoglycemia was reported, 22% were on SFU or metformin + SFU combination,
      and 2% were on metformin. CONCLUSIONS: The findings from this open-label, single
      arm study characterized the response to exenatide 10 MUg BID for up to 132 weeks.
      Significant, persistent improvements in HbA(1c) and weight were observed in
      patients receiving exenatide BID, with reported AEs consistent with those from
      studies of shorter duration. ClinicalTrials.gov identifier: NCT00044668.

PMID- 22608108
TI  - Calculating an intervention's (cost-)effectiveness for the real-world target
      population: the potential of combining strengths of both RCTs and observational
      data.
AB  - Economic evaluations most often use results from randomised controlled trials
      (RCTs) to model effectiveness. Inconsiderate application of the absolute
      treatment effect from RCTs may result in unrealistic estimates of an
      intervention's benefit for the real-world target population. The baseline risk of
      events in this target population may differ significantly from the baseline risk
      in the RCT population. An approach to handle this problem is to combine
      observational data with evidence from RCTs. Reliable administrative or register
      data can provide an estimate of the real-world baseline risks. In combination
      with the relative treatment effect from well-performed RCTs this results in an
      estimate of the absolute benefit for the relevant target population. Applying
      this approach, one must remain cautious about the validity of the assumption of a
      constant relative treatment effect.

PMID- 22608107
TI  - Efficacy and tolerability of once-daily oral fimasartan 20 to 240 mg/d in Korean
      Patients with hypertension: findings from Two Phase II, randomized, double-blind,
      placebo-controlled studies.
AB  - BACKGROUND: Fimasartan is a selective angiotensin II receptor blocker developed
      for once-daily dosing. OBJECTIVES: To meet the regulatory requirements for
      approval of an antihypertensive treatment in Korea, this pair of studies was
      conducted to evaluate the efficacy and tolerability of fimasartan, to determine
      its dose-response relationship and minimum effective dose, and to characterize
      its blood pressure (BP)-reduction profile over the dosing interval. METHODS:
      These 2 Phase II, randomized, double-blind, placebo-controlled, parallel-group,
      and dose-response studies enrolled male or nonchildbearing female Korean patients
      aged 18 to 65 years (study 1) or 18 to 70 years (study 2) with essential
      hypertension (sitting diastolic BP [DBP] 95-<115 mm Hg [study 1] or 90-<110 mm Hg
      [study 2]). Patients were randomly assigned to receive fimasartan 20, 60, 120, or
      180 mg (study 1) or 20, 60, 120, or 240 mg (study 2) or placebo in the same
      ratio, once daily for 4 weeks (study 1) or 8 weeks (study 2). Clinic BP was
      measured at trough, and change from baseline in DBP at week 4 (study 1) or 8
      (study 2) was the primary efficacy end point. In study 1, 24-hour ambulatory BP
      monitoring (ABPM) was conducted. Treatment-emergent adverse events (TEAEs) were
      assessed using a structured questionnaire, laboratory testing, physical
      examination, and ECG readings. RESULTS: Totals of 61 and 195 patients
      participated in studies 1 and 2, respectively (68% male; mean age, 50.1 and 55.1
      years; DBP, 98.7 and 103.6 mm Hg; systolic BP, 147.0 and 158.1 mm Hg), of whom 52
      (85.2%) and 169 (86.7%) completed each study. Data from ABPM were obtained from
      45 patients (73.8%), and safety profile was evaluated in 225 participants. Four
      week treatment with fimasartan 180 mg once daily was associated with a
      significantly greater mean reduction in DBP compared with placebo in study 1 (
      16.4 vs -5.5 mm Hg; P = 0.022). In study 2, fimasartan 60, 120, and 240 mg once
      daily were associated with significantly greater reductions in DBP after 8 weeks
      of treatment compared with placebo (-14.4, -14.1, and -12.7 vs -5.8 mm Hg,
      respectively; P < 0.0001-< 0.005). Fimasartan 60 mg once daily was the minimum
      effective dose, and the dose-response relationship was flat at doses >60 mg once
      daily. BP reduction was maintained over the full 24-hour dosing interval (trough
      to-peak ratios: 0.41-0.98). The proportions of patients who experienced TEAEs
      were comparable among the treatment groups in both studies, with headache (9.8%)
      and dizziness (4.4%) being most commonly reported. No serious AEs were reported.
      CONCLUSIONS: Once-daily oral administration of fimasartan was well tolerated and
      efficacious in reducing BP in these hypertensive Korean patient populations.
      ClinicalTrials.gov identifiers: NCT00937651 and NCT00923611.

PMID- 22608111
TI  - Diseases in aquatic crustaceans: problems and solutions for global food security.

PMID- 22608109
TI  - Low maternal hemoglobin during pregnancy and diminished neuromotor and
      neurocognitive performance in offspring with schizophrenia.
AB  - OBJECTIVE: Previous research has linked maternal anemia during pregnancy with
      increased risk for schizophrenia in offspring. However, no study has sought to
      determine whether this early insult leads to a more severe form of the disorder,
      characterized by worsened motor and neurocognitive functioning. METHOD: Subjects
      were 24 cases diagnosed with schizophrenia and 22 controls from the Developmental
      Insult and Brain Anomaly in Schizophrenia (DIBS) study. Hemoglobin values were
      measured throughout pregnancy. Among offspring, psychiatric diagnoses were
      determined through semi-structured interviews and medical records review and
      comprehensive neurocognitive assessment batteries were conducted in adulthood.
      RESULTS: Results indicated that among cases decreases in maternal hemoglobin led
      to significant decreases in scores on the Grooved Pegboard test, the Finger
      Tapping test and the Wechsler Adult Intelligent Scales (WAIS) information
      subtest. In contrast, controls only exhibited decreases in performance on the
      California Verbal Learning Test (CVLT) long-delay recall after fetal exposure to
      lower hemoglobin. There were also significant interactions between hemoglobin and
      case status for all of the motor tasks. CONCLUSIONS: These findings support the
      hypothesis that fetal exposure to decreases in maternal hemoglobin is related to
      preferentially poorer neuromotor function among cases compared to controls, as
      well as general intellectual difficulties among cases. Controls were relatively
      unaffected by decreased maternal hemoglobin, which suggests that liability to
      schizophrenia renders cases susceptible to the deleterious influences of in utero
      exposure to decreases in maternal hemoglobin.

PMID- 22608112
TI  - Why continuum electrostatics theories cannot explain biological structure,
      polyelectrolytes or ionic strength effects in ion-protein interactions.
AB  - Continuum electrostatics models for ions in water provide apparent long range
      electrostatic explanations for the forces on ions. However the electro-chemical
      free energy of solvation of ions resides largely in the first two water layers,
      which control the interfacial behavior of the ions and require explicit modeling
      to capture their distinctive behaviors. The resulting short range forces produce
      such surprising charge density-dependent behaviors as ion adsorption onto
      nonpolar surfaces, like charge aggregation of ions, and substantial ion pairing
      preferences, which arise largely from the affinity of specific ions for
      individual water molecules. Specific ion effects controlled by the local water
      affinity of the ion show a diagnostic change of sign between strongly hydrated
      Na(+) and weakly hydrated K(+) and between strongly hydrated F(-) and weakly
      hydrated Cl(-), in both cases marking the strength of water-water interactions in
      bulk solution, a critical benchmark missing from continuum electrostatics models.

PMID- 22608110
TI  - Nocturnin: at the crossroads of clocks and metabolism.
AB  - Many aspects of metabolism exhibit daily rhythmicity under the control of
      endogenous circadian clocks, and disruptions in circadian timing result in
      dysfunctions associated with the metabolic syndrome. Nocturnin (Noc) is a
      robustly rhythmic gene that encodes a deadenylase thought to be involved in the
      removal of polyA tails from mRNAs. Mice lacking the Noc gene display resistance
      to diet-induced obesity and hepatic steatosis, due in part to reduced lipid
      trafficking in the small intestine. In addition, Noc appears to play important
      roles in other tissues and has been implicated in lipid metabolism, adipogenesis,
      glucose homeostasis, inflammation and osteogenesis. Therefore, Noc is a potential
      key post-transcriptional mediator in the circadian control of many metabolic
      processes.

PMID- 22608113
TI  - Differential recognition by tick-resistant cattle of the recombinantly expressed
      Rhipicephalus microplus serine protease inhibitor-3 (RMS-3).
AB  - Rhipicephalus microplus is an important bovine ectoparasite, widely distributed
      in tropical and subtropical regions of the world causing large economic losses to
      the cattle industry. Its success as an ectoparasite is associated with its
      capacity to disarm the antihemostatic and anti-inflammatory reactions of the
      host. Serpins are protease inhibitors with an important role in the modulation of
      host-parasite interactions. The cDNA that encodes for a R. microplus serpin was
      isolated by RACE and subsequently cloned into the pPICZalphaA vector. Sequence
      analysis of the cDNA and predicted amino acid showed that this cDNA has a
      conserved serpin domain. B- and T-cell epitopes were predicted using
      bioinformatics tools. The recombinant R. microplus serpin (rRMS-3) was secreted
      into the culture media of Pichia pastoris after methanol induction at 0.2 mg l(
      1). qRT-PCR expression analysis of tissues and life cycle stages demonstrated
      that RMS-3 was mainly expressed in the salivary glands of female adult ticks.
      Immunological recognition of the rRMS-3 and predicted B-cell epitopes was tested
      using tick-resistant and susceptible cattle sera. Only sera from tick-resistant
      bovines recognized the B-cell epitope AHYNPPPPIEFT (Seq7). The recombinant RMS-3
      was expressed in P. pastoris, and ELISA screening also showed higher recognition
      by tick-resistant bovine sera. The results obtained suggest that RMS-3 is highly
      and specifically secreted into the bite site of R. microplus feeding on tick
      resistant bovines. Capillary feeding of semi-engorged ticks with anti
      AHYNPPPPIEFT sheep sera led to an 81.16% reduction in the reproduction capacity
      of R. microplus. Therefore, it is possible to conclude that R. microplus serpin
      (RMS-3) has an important role in the host-parasite interaction to overcome the
      immune responses in resistant cattle.

PMID- 22608114
TI  - Detection of European strain of Echinococcus multilocularis in North America.

PMID- 22608115
TI  - Cost-effectiveness and long-term effectiveness of internet-based cognitive
      behaviour therapy for severe health anxiety.
AB  - BACKGROUND: Severe health anxiety is a common condition associated with
      functional disability, making it a costly disorder from a societal perspective.
      Internet-based cognitive behaviour therapy (ICBT) is a promising treatment but no
      previous study has assessed the cost-effectiveness or long-term outcome of ICBT
      for severe health anxiety. The aim of this study was to investigate the cost
      effectiveness and 1-year treatment effects of ICBT for severe health anxiety.
      METHOD: Cost-effectiveness and 1-year follow-up data were obtained from a
      randomized controlled trial (RCT) comparing ICBT (n = 40) to an attention control
      condition (CC, n = 41). The primary outcome measure was the Health Anxiety
      Inventory (HAI). A societal perspective was taken and incremental cost
      effectiveness ratios (ICERs) were calculated using bootstrap sampling. RESULTS:
      The main ICER was -L1244, indicating the societal economic gain for each
      additional case of remission when administering ICBT. Baseline to 1-year follow
      up effect sizes on the primary outcome measure were large (d = 1.71-1.95).
      CONCLUSIONS: ICBT is a cost-effective treatment for severe health anxiety that
      can produce substantial and enduring effects.

PMID- 22608116
TI  - Sequential determination of fat- and water-soluble vitamins in green leafy
      vegetables during storage.
AB  - The simultaneous analysis of fat- and water-soluble vitamins from foods is a
      difficult task considering the wide range of chemical structures involved. In
      this work, a new procedure based on a sequential extraction and analysis of both
      types of vitamins is presented. The procedure couples several simple extraction
      steps to LC-MS/MS and LC-DAD in order to quantify the free vitamins contents in
      fresh-cut vegetables before and after a 10-days storage period. The developed
      method allows the correct quantification of vitamins C, B(1), B(2), B(3), B(5),
      B(6), B(9), E and provitamin A in ready-to-eat green leafy vegetable products
      including green lettuce, ruby red lettuce, watercress, swiss chard, lamb's
      lettuce, spearmint, spinach, wild rocket, pea leaves, mizuna, garden cress and
      red mustard. Using this optimized methodology, low LOQs were attained for the
      analyzed vitamins in less than 100 min, including extraction and vitamin analysis
      using 2 optimized procedures; good repeatability and linearity was achieved for
      all vitamins studied, while recoveries ranged from 83% to 105%. The most abundant
      free vitamins found in leafy vegetable products were vitamin C, provitamin A and
      vitamin E. The richest sample on vitamin C and provitamin A was pea leaves (154
      mg/g fresh weight and 14.4 mg/100g fresh weight, respectively), whereas lamb's
      lettuce was the vegetable with the highest content on vitamin E (3.1 mg/100 g
      fresh weight). Generally, some losses of vitamins were detected after storage,
      although the behavior of each vitamin varied strongly among samples.

PMID- 22608118
TI  - Tick-borne illnesses: an overview.

PMID- 22608119
TI  - When to suspect tick-borne illness.

PMID- 22608120
TI  - Lyme disease.

PMID- 22608121
TI  - Ehrlichioses: anaplasmosis and human ehrlichiosis.

PMID- 22608122
TI  - Babesiosis.

PMID- 22608123
TI  - Rocky Mountain spotted fever.

PMID- 22608124
TI  - Other tick-borne illnesses: tularemia, Colorado tick fever, tick paralysis.

PMID- 22608125
TI  - Prevention of tick-borne illness.

PMID- 22608126
TI  - Suppression of IP-10/CXCL10 gene expression in LPS- and/or IFN-gamma-stimulated
      macrophages by parasite-secreted products.
AB  - T helper (Th)2 polarized immune responses are characteristically dominant in
      helminth infections. The gene expression of interferon (IFN)-gamma-inducible
      protein 10 (IP-10/CXCL10), which promotes Th1 responses, in mouse macrophages
      stimulated with lipopolysaccharide (LPS) and/or IFN-gamma was suppressed by
      excretory/secretory (ES) products of Spirometra erinaceieuropaei plerocercoids.
      ES products suppressed LPS- and/or IFN-gamma-induced transcriptional activities
      of a luciferase reporter gene under the control of a 243-bp fragment of the IP-10
      gene promoter/enhancer, which contains an IFN-stimulated response element (ISRE)
      and two kappaB elements. Consistent with this result, ES products inhibited ISRE
      dependent heterologous promoter activities and LPS- or IFN-gamma-induced ISRE
      binding activity. ES products also suppressed LPS-induced IFN-beta gene
      expression. Furthermore, ES products suppressed nuclear factor (NF)-kappaB RelA
      (p65)-dependent transcriptional activity, whereas ES products had no effect on
      the kappaB-binding activity. These results suggest that ES products suppress the
      IP-10 gene expression by inhibiting the ISRE- and RelA-dependent transcriptional
      activities in mouse macrophages.

PMID- 22608127
TI  - Transcriptome and gene expression analysis in cold-acclimated guayule (Parthenium
      argentatum) rubber-producing tissue.
AB  - Natural rubber biosynthesis in guayule (Parthenium argentatum Gray) is associated
      with moderately cold night temperatures. To begin to dissect the molecular events
      triggered by cold temperatures that govern rubber synthesis induction in guayule,
      the transcriptome of bark tissue, where rubber is produced, was investigated. A
      total of 11,748 quality expressed sequence tags (ESTs) were obtained. The vast
      majority of ESTs encoded proteins that are similar to stress-related proteins,
      whereas those encoding rubber biosynthesis-related proteins comprised just over
      one percent of the ESTs. Sequence information derived from the ESTs was used to
      design primers for quantitative analysis of the expression of genes that encode
      selected enzymes and proteins with potential impact on rubber biosynthesis in
      field-grown guayule plants, including 3-hydroxy-3-methylglutaryl-CoA synthase, 3
      hydroxy-3-methylglutaryl-CoA reductase, farnesyl pyrophosphate synthase, squalene
      synthase, small rubber particle protein, allene oxide synthase, and cis-prenyl
      transferase. Gene expression was studied for field-grown plants during the normal
      course of seasonal variation in temperature (monthly average maximum 41.7 
      degrees C to minimum 0  degrees C, from November 2005 through March 2007) and
      rubber transferase enzymatic activity was also evaluated. Levels of gene
      expression did not correlate with air temperatures nor with rubber transferase
      activity. Interestingly, a sudden increase in night temperature 10 days before
      harvest took place in advance of the highest CPT gene expression level.

PMID- 22608128
TI  - A review of the chemistry of the genus Crataegus.
AB  - Since the 1800s, natural health products that contain hawthorn (Crataegus spp.)
      have been used in North America for the treatment of heart problems such as
      hypertension, angina, arrhythmia, and congestive heart failure. Traditionally,
      Native American tribes used hawthorn (Crataegus spp.) to treat gastrointestinal
      ailments and heart problems, and consumed the fruit as food. Hawthorn also has a
      long history of use in Europe and China for food, and in traditional medicine.
      Investigations of Crataegus spp. typically focus on the identification and
      quantification of flavonoids and anthocyanins, which have been shown to have
      pharmacological activity. The main flavonoids found in Crataegus spp. are
      hyperoside, vitexin, and additional glycosylated derivatives of these compounds.
      Reviewed herein are the botany, ethnobotany, and traditional use of hawthorn
      while focusing on the phytochemicals that have been reported in Crataegus
      species, and the variation in the described chemistry between individual species.

PMID- 22608129
TI  - Advanced nursing interventions and length of stay in the emergency department.
AB  - INTRODUCTION: Over the past 15 years, emergency departments have become
      overcrowded, with prolonged wait times and an extended length of stay (LOS).
      These factors cause delay in treatment, which reduces quality of care and
      increases the potential for adverse events. One suggestion to decrease LOS in the
      emergency department is to implement advanced nursing interventions (ANIs) at
      triage. The study purpose was to determine whether there was a difference in ED
      LOS between patients presenting with a chief complaint of abdominal pain who
      received ANIs at triage and patients who did not receive ANIs at triage. METHODS:
      A retrospective chart review was performed to determine the ED LOS (mean time in
      department and mean time in room [TIR]). The convenience sample included ED
      patients who presented to a large Midwestern academic medical center's emergency
      department with a chief complaint of abdominal pain and Emergency Severity Index
      level 3. Independent-samples t tests were used to determine whether there was any
      statistical difference in LOS between the two groups. Cohen's d statistic was
      used to determine effect size. RESULTS: Implementation of ANIs at triage for
      patients with low-acuity abdominal pain resulted in an increased time in
      department and a decreased TIR with a medium effect size. CONCLUSION: A reduction
      in TIR optimizes bed availability in the emergency department. Low-acuity
      patients spend less time occupying an ED bed, which preserves limited bed space
      for the sickest patients. Results of diagnostic tests are often available by the
      time the patient is placed in a room, facilitating early medical decision making
      and decreasing treatment time.

PMID- 22608130
TI  - Introduction of farm stands in low-income communities increases fruit and
      vegetable among community residents.
AB  - The purpose of this longitudinal pilot study was to measure the impact of
      introducing farm stands in low-income communities with limited access to fresh
      and quality fruits and vegetables (F&V) on residents' F&V consumption. Two farm
      stands were placed outside two local community sites one day a week for 12 weeks.
      A variety of locally grown, culturally appropriate produce was sold at the
      stands. Data on F&V intake, awareness and usage of farmers' markets, family
      behaviors, and importance of eating F&V were collected from individuals (n=61)
      before and after farm stands were placed in the two communities. Paired sample t
      tests, chi-square and McNemar tests were used to evaluate the impact of the
      intervention on the outcome variables. Significance level was set at p<.05.
      Significant increases were found for participants' consumption of fruit, fruit
      juice, tomatoes, green salad, and other vegetables (P<.05). Additionally,
      participants also reported increases in mediating variables of F&V consumption.
      This study underscores the potential of farmers' markets to increase F&V
      consumption through increasing F&V access in low-income communities.

PMID- 22608131
TI  - Development of a novel rDNA based plasmid for enhanced cell surface display on
      Yarrowia lipolytica.
AB  - In this study, a novel rDNA based plasmid was developed for display of
      heterologous proteins on the cell surface of Yarrowia lipolytica using the C
      terminal end of the glycosylphosphatidylinositol (GPI) anchored Y. lipolytica
      cell wall protein 1 (YlCWP1). mCherry was used as a model protein to assess the
      efficiency of the constructed plasmid. Y. lipolytica transformants harbouring the
      expression cassettes showed a purple colour phenotype on selective YNB-casamino
      plates as compared to control cells indicating that mCherry was displayed on the
      cells. Expression of mCherry on cells of Y. lipolytica was confirmed by both
      fluorescent microscopy and flow cytometry. Furthermore, SDS-PAGE analysis and
      matrix-assisted laser desorption/ionization (MALDI)-time-of (TOF)-mass
      spectrometry (MS) peptide mass fingerprinting (PMF) confirmed that the protein
      cleaved from the yeast cells using enterokinase was mCherry. Efficient cleavage
      of mCherry reported in this work offers an alternative purification method for
      displayed heterologous proteins on Y. lipolytica cells using the plasmid
      constructed in this study. The developed displaying system offers great potential
      for industrial production and purification of heterologous proteins at low cost.

PMID- 22608132
TI  - Selenium speciation and localization in chironomids from lakes receiving treated
      metal mine effluent.
AB  - A lake system in northern Saskatchewan receiving treated metal mine and mill
      effluent contains elevated levels of selenium (Se). An important step in the
      trophic transfer of Se is the bioaccumulation of Se by benthic invertebrates,
      especially primary consumers serving as a food source for higher trophic level
      organisms. Chironomids, ubiquitous components of many northern aquatic
      ecosystems, were sampled at lakes downstream of the milling operation and were
      found to contain Se concentrations ranging from 7 to 80 mgkg(-1)dry weight. For
      comparison, laboratory-reared Chironomus dilutus were exposed to waterborne
      selenate, selenite, or seleno-DL-methionine under laboratory conditions at the
      average total Se concentrations found in lakes near the operation. Similarities
      in Se localization and speciation in laboratory and field chironomids were
      observed using synchrotron-based X-ray fluorescence (XRF) imaging and X-ray
      absorption spectroscopy (XAS). Selenium localized primarily in the head capsule,
      brain, salivary glands and gut lining, with organic Se species modeled as
      selenocystine and selenomethionine being the most abundant. Similarities between
      field chironomids and C. dilutus exposed in the laboratory to waterborne
      selenomethionine suggest that selenomethionine-like species are most readily
      accumulated, whether from diet or water.

PMID- 22608133
TI  - Investigation of trace metal binding properties of lignin by diffusive gradients
      in thin films.
AB  - The binding behavior of lignin for Pb, Cu, Co, Mn, Cd and Ni was studied using
      the diffusive gradients in thin films technique (DGT). Samplers with different
      structures of diffusive gel were used in the well-stirred systems containing
      known concentrations of metals along with (a) 10, 20 and 40 MUM lignin and; (b)
      0.64 and 6.47 MUM Suwannee river fulvic acid+40 MUM lignin at an ionic strength
      of 0.01 M (NaNO(3)) and pH=7. Diffusion coefficients of lignin complexes in
      acrylamide gels were estimated and found to be less than 5% of the equivalent
      coefficients for the uncomplexed metal ions. These values were used to calculate
      concentrations of labile metals from DGT measurements in solutions, where lignin
      could discriminate metals in the order of
      Pb(+2)>Cu(+2)>Cd(+2)>Ni(+2)>Co(+2)>Mn(+2). Stability constants (LogK) were
      calculated using Visual MINTEQ II and WHAM V software. The K values were compared
      with the stability constants from titration of Pb and Cd with 10 MUM lignin
      aqueous samples and with those of humic substances in natural waters. The
      constants obtained from measurement of complexing capacities might bias the real
      corresponding values unless two line regression analyses on titration data are
      considered. The DGT study of fractionation of metal species at varying ratios
      indicated that the proportion of organic complexes decreased with increasing
      ratios and gradually more metals were exchanged with inorganic phases. Speciation
      of Pb and Cd is affected by the concentrations of FA, Cd is dominantly bound with
      FA while Pb is evenly partitioned between the ligands. The comprehensive
      knowledge of metal-lignin complexes sheds some light on in situ operational
      speciation information that can be achieved by DGT.

PMID- 22608134
TI  - Removal of Ni(II) and Cu(II) ions using native and acid treated Ni
      hyperaccumulator plant Alyssum discolor from Turkish serpentine soil.
AB  - Alyssum discolor biomass was collected from serpentine soil and was used for
      removal of metal ions. The plant species grown on serpentine soils are known to
      be rich with metals ions and thus have more capability for accumulating heavy
      metals. Native and acid-treated biomass of A. discolor (A. discolor) were
      utilized for the removal of Ni(II) and Cu(II) ions from aqueous solutions. The
      effects of contact time, initial concentration, and pH on the biosorption of
      Ni(II) and Cu(II) ions were investigated. Biosorption equilibrium was established
      in about 60 min. The surface properties of the biomass preparations were varied
      with pH, and the maximum amounts of Ni(II) and Cu(II) ions on both A. discolor
      biomass preparations were adsorbed at pH 5.0. The maximum biosorption capacities
      of the native, and acid-treated biomass preparations for Ni(II) were 13.1 and
      34.7 mgg(-1) and for Cu(II) 6.15 and 17.8 mgg(-1) dry biomass, respectively. The
      biosorption of Ni(II) and Cu(II) ions from single and binary component systems
      can be successfully described by Langmuir and Freundlich isotherms. When the
      heavy metal ions were in competition, the amounts of biosorbed metal ions on the
      acid treated plant biomass were found to be 0.542 mmolg(-1) for Ni(II) and 0.162
      mmolg(-1) for Cu(II), the A. discolor biomass was significantly selective for
      Ni(II) ions. The information gained from these studies was expected to indicate
      whether the native, and acid-treated forms can have the potential to be used for
      the removal and recovery of Ni(II) ions from wastewaters.

PMID- 22608135
TI  - Phytoavailability and geospeciation of cadmium in contaminated soil remediated by
      Rhodobacter sphaeroides.
AB  - A microorganism was isolated from oil field injection water and identified as
      Rhodobacter sphaeroides. It was used for the remediation of simulated cadmium
      contaminated soil. The phytoavailability of Cd was investigated through wheat
      seedling method to determine the efficiency of remediation. It was found that
      after remediation, the accumulation of Cd in wheat roots and leaves decreased by
      67% and 53%, respectively. The Cd speciation in soil was determined with Tessier
      extraction procedure. It was found that the total Cd content in soil did not
      change during the experiments, but the geo-speciation of Cd changed remarkably.
      Among the five fractions, the concentration of exchangeable phases decreased by
      27-46% and that of the phases bound to Fe-Mn oxides increased by 22-44%. The
      decrease of Cd accumulation in wheat showed significant positive correlation with
      the decrease of exchangeable phases. It could be concluded that the remediation
      of R. sphaeroides was carried out through the conversion of Cd to more stable
      forms. The decrease of sulfate concentration in supernatant indicated that the R.
      sphaeroides consumed sulfate.

PMID- 22608136
TI  - In vitro efficacy of the combination of voriconazole and anidulafungin against
      voriconazole-resistant cyp51A mutants of Aspergillus fumigatus.
AB  - We selected voriconazole-resistant (VCZ-R) Aspergillus fumigatus in the
      laboratory, characterized the cyp51A gene for possible mutations and evaluated
      the in vitro activities of voriconazole and anidulafungin alone and in
      combination against VCZ-R isolates of A. fumigatus using a fractional inhibitory
      concentration index (FICI) methodology. Voriconazole-resistant isolates were
      selected from wild-type A. fumigatus isolates in the laboratory by a 2-step
      selection process (plus 1 clinical isolate). The MICs of azoles (VCZ,
      posaconazole, itraconazole) and echinocandins (anidulafungin, micafungin, and
      caspofungin) for all A. fumigatus isolates were then determined in RPMI1640 using
      the broth microdilution technique recommended by the Clinical Laboratory and
      Standards Institute M38-A2 methodology and the FICI calculated. The combination
      of VCZ and anidulafungin was synergistic (FICI <0.5) not only against VCZ
      susceptible isolates, but also against 8 of 10 VCZ-R, G448S mutants of A.
      fumigatus. The combination demonstrated synergy against the VCZ-R clinical
      isolate as well.

PMID- 22608137
TI  - Antimicrobial activity of daptomycin in comparison to glycopeptides and other
      antimicrobials when tested against numerous species of coagulase-negative
      Staphylococcus.
AB  - Coagulase-negative Staphylococcus spp. (CoNS) represent a major cause of
      bloodstream infections, especially in patients with prosthetic devices and
      intravenous catheters. We evaluated the activity of daptomycin in comparison to
      vancomycin and teicoplanin against a large collection of 22,024 CoNS isolates
      causing clinically significant infections from 283 medical centers over 9 years
      (2002-2010) and tested for susceptibility by broth microdilution methods against
      daptomycin and numerous comparators. Overall, daptomycin (MIC(50/90), 0.25/0.5
      MUg/mL) inhibited 99.8% of CoNS at the susceptible breakpoint of <=1 MUg/mL and
      was 4- to 16-fold more active than vancomycin (MIC(50/90), 1/2 MUg/mL; >99.9%
      susceptible). All species showed >=99.6% susceptibility to daptomycin, except
      Staphylococcus auricularis (95.1%), S. capitis (99.0%), S. warneri (98.8%), and
      S. sciuri. S.sciuri represented only 0.2% of the collection (46 strains) and
      exhibited decreased susceptibility to daptomycin (MIC(50/90), 1/2 MUg/mL; 71.7%
      susceptible). In contrast, S. sciuri exhibited high susceptibility to vancomycin
      and teicoplanin (highest MIC at 2 MUg/mL for both drugs). In summary, daptomycin
      exhibited species-specific activity among CoNS, especially versus S. sciuri. No
      correlation between decreased susceptibility to daptomycin and the glycopeptides
      tested was observed.

PMID- 22608138
TI  - Spinosad: a biorational mosquito larvicide for use in car tires in southern
      Mexico.
AB  - BACKGROUND: Car tires are important habitats for mosquito development because of
      the high density populations they can harbor and their presence in urban
      settings. Water in experimental tires was treated with one of three insecticides
      or an untreated control. Aquatic invertebrates were sampled at weekly intervals.
      Eggs, larval and pupal samples were laboratory-reared to estimate seasonal
      fluctuations in Aedes aegypti and Ae. albopictus abundance. RESULTS: Spinosad
      treatments at 1 or 5 ppm (mg a.i./liter) provided 6-8 weeks of effective control
      of Ae. aegypti, Ae. albopictus, Culex quinquefasiatus and Cx. coronator larvae,
      both in the dry season and the rainy season when mosquito populations increased
      markedly in southern Mexico. Spinosad continued to provide partial control of
      larvae for several weeks after initial recolonization of treated tires. The
      larvicidal performance of VectoBac 12AS (Bacillus thuringiensis var. israelensis)
      was relatively poor with one week of complete control of Aedes spp. larvae and no
      discernible control of Culex spp., whereas the duration of larvicidal activity of
      1% temephos mineral-based granules was intermediate between those of VectoBac and
      spinosad treatments. Populations of chironomids, ostracods and Toxorhynchites
      theobaldi were generally reduced in spinosad and temephos treatments, but were
      similar in control and VectoBac treatments. CONCLUSION: The present study is the
      first to report spinosad as an effective larvicide against Cx. coronator, which
      is currently invading the southern United States. These results substantiate the
      use of spinosad as a highly effective mosquito larvicide, even in habitats such
      as unused car tires that can represent prolific sources of adult mosquitoes.

PMID- 22608139
TI  - Serotonin as a homeostatic regulator of lactation.
AB  - Serotonin (5-HT), a neurotransmitter produced in mammary epithelial cells (MECs),
      acts via autocrine-paracrine mechanisms on MECs to regulate milk secretion in a
      variety of species. Recent studies in dairy cows reported that 5-HT ligands
      affect milk yield and composition. We determined the mRNA expression of bovine 5
      HT receptor (5-HTR) subtypes in bovine mammary tissue (BMT) and cultured bovine
      MECs. We then used pharmacologic agents to evaluate functional activities of 5
      HTR subtypes. The mRNAs for five receptor isoforms (5-HTR1B, 5-HTR2A, 5-HTR2B, 5
      HTR4, and 5-HTR7) were identified by conventional reverse transcription PCR, real
      time PCR, and in situ hybridization in BMT. In addition to luminal MEC
      expression, 5-HTR4 was expressed in myoepithelium, and 5-HTR1B, HTR2A, and HTR2B
      were expressed in small mammary blood vessels. Studies to date report that there
      are multiple 5-HTR isoforms in mammary tissue of rodents, humans, and cattle.
      Inhibition of the 5-HT reuptake transporter with selective 5-HT reuptake
      inhibitors (SSRIs) disrupted tight junctions and decreased milk protein mRNA
      expression in mouse, human, and bovine mammary cells. Selective 5-HT reuptake
      inhibitors act to increase the cellular exposure to 5-HT by preventing reuptake
      of 5-HT by the cell and eventual degradation. Increasing 5-HT concentration in
      milk via inhibiting its reuptake (SSRI), or by increasing the precursor for 5-HT
      synthesis 5-hydroxytryptophan, accelerated decline in milk synthesis at dry-off.
      We conclude that the 5-HT system in mammary tissue acts as a homeostatic
      regulator of lactation.

PMID- 22608141
TI  - Increase of regulatory T cells in metastatic stage and CTLA-4 over expression in
      lymphocytes of patients with non-small cell lung cancer (NSCLC).
AB  - We hypothesized that the increased percentages of Regulatory T (Treg) cells, as
      well as over expression of Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) by
      lymphocyte subsets might be associated with lung cancer. Accordingly, peripheral
      blood of 23 new cases with non-small cell lung cancer (NSCLC) and 16 healthy
      volunteers were investigated, by follow cytometry, for the prevalence of
      CD4+CD25+FoxP3+ Treg cells as well as surface (sur-) and intracellular (In-)
      expression of CTLA-4 by the main lymphocyte subsets (CD4+, CD8+ and CD19+).
      Results indicated that NSCLC patients had an increased percentage of Treg cells
      than controls (7.9+/-4.1 versus 3.8+/-1.8, P=0.001). The proportion of Treg cells
      was observed to be increased by stage increase in patients (stage II=5.2+/-2.4,
      stage III=7.9+/-4.4, stage IV=12.0+/-2.2), and also significantly higher in
      metastatic than non-metastatic stages (12.0+/-2.2 versus 6.8+/-3.9, P=0.023).
      Increase of SurCTLA-4- as well as InCTLA-4-expressing lymphocytes in patients
      were observed in nearly all investigated subsets, but significant differences
      between patients and controls were observed about InCTLA-4+CD4+ lymphocytes
      (8.6+/-7.1 and 3.8+/-5.3 respectively, P=0.006) as well as SurCTLA-4+CD8+
      lymphocytes (0.3+/-0.2 and 0.2+/-0.1 respectively, P=0.047). In conclusion, the
      results suggest that immunotherapy regimen targeting CTLA-4 and Treg cells might
      be beneficial in lung cancer patients.

PMID- 22608140
TI  - Longitudinal association between early life socio-environmental factors and
      attention function at the age 11 years.
AB  - Prenatal and early-life exposures can affect the course of children's
      neuropsychological development well into pre-adolescence, given the vulnerability
      of the developing brain. However, it is unknown which socio-environmental factors
      at early childhood can influence specific cognitive processes like attention at a
      later age. In this study, we aim to determine social and environmental exposures
      in early childhood that may be associated with attention function of 11-year
      olds. We measured attention function using the continuous performance test-II
      (CPT-II) on 393 11-year old children from the Menorca's birth-cohort within the
      INMA-project (Spain), and pre-selected a list of socio-environmental observations
      taken when they were up to 4 years of age. We found that earlier socio
      environmental characteristics, such as parental social class, educational level
      and maternal mental health are associated with later inattentive and impulsive
      symptomatology through a higher rate of omission and commission errors. In
      addition, omission errors were higher in children with atopy and lower in those
      whose mothers took dietary supplementation with folic acid and vitamins during
      pregnancy. Breastfeeding played a protective role against commission errors,
      while higher DDE and PCBs levels at age 4 were associated with slow speed
      response. Our findings suggest that a number of life socio-environmental factors
      during prenatal life and early childhood, such as socio-demographic
      characteristics, breastfeeding, maternal nutritional supplementation with folic
      acid and vitamins and exposure to some organochlorine compounds may influence
      inattentive and hyperactive/impulsive symptomatology during pre-adolescence.

PMID- 22608142
TI  - Non-steroidal anti-inflammatory drugs and small cell lung cancer risk in the
      VITAL study.
AB  - Few studies have examined the association between non-steroidal anti-inflammatory
      drug (NSAID) use and risk of small cell lung cancer (SCLC); among them, findings
      are mixed. Recently, we found that use of NSAIDs was differentially associated
      with lung cancer risk by histology. Here, we examine, more comprehensively, the
      association between individual NSAIDs and SCLC risk. 75,546 residents of western
      Washington State, ages 50-76, completed a baseline questionnaire in 2000-2002 and
      reported on their use of individual NSAIDs over the past 10 years. NSAID use was
      categorized as non-users, low (<4 days/week or <4 years), and high (>=4 days/week
      and >=4 years). 111 SCLC were identified through linkage to a population-based
      cancer registry. Multivariable-adjusted Cox proportional hazards models including
      strong adjustment for smoking were used to estimate hazard ratios (HR) and 95%
      confidence intervals (95% CI). Compared to non-use, high use of regular-strength
      aspirin was associated with an elevated risk of SCLC (HR 1.78, 95% CI: 1.05-3.02;
      P-trend=0.03). Findings for low-dose aspirin were elevated but did not reach
      statistical significance. Use of non-aspirin NSAIDs was not associated with SCLC
      risk. Our findings provide further indication of heterogeneity in the association
      between aspirin and lung cancer morphologies. Large, prospective studies with
      comprehensive assessments of NSAID use and smoking history and data on both men
      and women, are needed in order to better understand the association between use
      of aspirin and SCLC.

PMID- 22608143
TI  - Spontaneous vesicles, disks, threadlike and spherical micelles found in the
      solubilization of DMPC liposomes by the detergent DTAC.
AB  - The spontaneous colloidal nanostructures formed in water by the zwitterionic
      phospholipid DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) with the cationic
      detergent DTAC (n-dodecyltrimethylammonium chloride) were investigated at a fixed
      DMPC concentration and variable detergent:lipid total molar ratios (D:L).
      Apparent (neutral-sphere-equivalent) hydrodynamic diameters (Phi(e)) of liposomes
      and micelles were obtained by dynamic light scattering (DLS). Fluorescence
      lifetime imaging microscopy (FLIM), using chlorophyll-a as a probe, showed the
      morphology of giant vesicles and threadlike micelles. Micro-differential scanning
      calorimetry (micro-DSC) detected the presence of bilayers, in vesicles and
      discoidal micelles (disks). Pure DMPC liposomes are multilamellar and
      polydisperse (Phi(e)~100-10,000 nm). As D:L increased, smaller vesicles were
      found, due to the bigger spontaneous curvature of the bilayer: at D:L=1, ULVs
      (unilamellar vesicles; Phi(e)~100 nm) appeared and, at D:L=2-10, ULVs coexisted
      with disks (Phi(e)~30 nm). Bilayers totally disappeared at D:L>=15, giving rise
      to spheroidal (Phi(e)~2-16 nm) and threadlike (Phi(e)~100-10,000 nm) micelles. A
      quasi-equilibrium structural diagram for the DMPC-DTAC-water system shows
      equivalent diameters of the scattering nanoparticles as a function of D:L. The
      results obtained herein for the system DMPC-DTAC show the role of electrostatic
      interactions in the formation of the mixed structures.

PMID- 22608144
TI  - Polyethylene glycol aggregates in water formed through hydrophobic helical
      structures.
AB  - The present study was aimed at elucidating the mechanism of aggregation in water
      of hydroxyl-terminated polyethylene glycol (PEG) of low molecular weight (600
      g/mol). The results from fluorescence spectroscopy at different temperatures were
      consistent with surface tension measurements, suggesting aggregate formation.
      Indeed, the process of aggregation is accompanied by an increase in the
      fluorescence emission of a hydrophobic probe. So, PEG aggregates in the form of
      internal hydrated helices covered with CH(2) groups are shown to yield
      hydrophobic regions. These regions created upon PEG aggregation in water and at a
      temperature close to 35 degrees C result from a balance between H bonding and
      entropic effects. By providing the first experimental evidence for hydrophobic
      mediation of aggregation with OH-terminated oxy-ethylene chains of low molecular
      weight, this study highlights their surfactant-like behaviour.

PMID- 22608145
TI  - Surface forces in thin liquid films of n-alcohols and of water-ethanol mixtures
      confined between hydrophobic surfaces.
AB  - An atomic force microscope (AFM) was used to measure the surface forces in thin
      liquid films (TLFs) confined between gold surfaces hydrophobized by chemisorption
      of alkylthiols. The measurements were conducted in different H-bonding liquids
      and in water-ethanol solutions. Attractive forces stronger and longer-ranged than
      the van der Waals force were observed in water, ethanol, and 1-butanol in a
      descending order. The attractive force measured in methanol was much weaker. The
      surface forces measured in ethanol solutions varied with concentration.
      Initially, the attractive forces decreased rapidly upon ethanol addition, passed
      through a broad minimum centered around mole fractions in the range of 0.15-0.20,
      and then increased as the ethanol mole fraction was further increased above ~0.5.
      Thermodynamic analysis of the data suggests that clusters of water and ethanol
      may form in TLFs. Thus, the attractive forces may arise from changes in liquid
      structure. It appears that structuring is a consequence of H-bonding liquid to
      minimize its free energy in the vicinity of hydrophobic surfaces and in the
      presence of foreign species in solution.

PMID- 22608146
TI  - Adsorption of Mefp-1: influence of pH on adsorption kinetics and adsorbed amount.
AB  - Mussel adhesive proteins have received considerable attention due to their
      ability to bind strongly to many surfaces under water. Key structural features of
      these proteins include a large number of 3,4-dihydroxyphenyl-L-ALANIN (DOPA) and
      positively charged lysine residues. We elucidate the effects of solution pH, in
      the pH range 3-9, on adsorption kinetics, adsorbed amount, and layer structure on
      silicon oxynitride by employing Dual Polarization Interferometry. As a
      comparison, the cationic globular protein lysozyme was also investigated. The
      zeta-potential of the silicon oxynitride substrate was determined as a function
      of pH, and the isoelectric point was found to be below pH 3. Mefp-1 is positively
      charged at pH<10, and thus, the protein is expected to have an electrostatic
      attraction for the surface at all pH values investigated. The adsorbed amount and
      the initial adsorption rate were found to increase with solution pH, and no
      significant desorption occurred due to rinsing with pure water. The layer
      thickness after rinsing was 3-4 nm, except at pH 3, where the adsorption was
      limited to a small amount. Covalent cross-linking of the Mefp-1 layer with
      NaIO(4) resulted in a small but significant compaction and increase in refractive
      index of the layer. The results are discussed in terms of the role of DOPA and
      electrostatic interactions for the adsorption of Mefp-1 to silicon oxynitride.

PMID- 22608147
TI  - Hybrid magnetic amphiphilic composites based on carbon nanotube/nanofibers and
      layered silicates fragments as efficient adsorbent for ethynilestradiol.
AB  - In this work, hybrid magnetic amphiphilic composites were prepared by the
      catalytic growth of carbon nanotubes (CNTs) and nanofibers CNF on layered
      silicates fragments. SEM, TEM, Raman, XRD, Mossbauer, TG/DTA showed that CVD with
      CH(4) at 800 degrees C produced CNF and magnetic Fe cores fixed on the surface of
      microfragments of silicates layers. Due to the amphiphilic character, the
      composites can be easily dispersed in water and efficiently adsorb hydrophobic
      contaminant molecules. For example, the composites showed remarkable adsorption
      capacities for the hormone ethinylestradiol, e.g. 2-4 mg m(-2), compared to ca.
      0.1 mg m(-2) obtained for high surface area activated carbon and multiwall CNT.
      These results are discussed in terms of a high hydrophobic exposed surface area
      of the CNT and CNF fixed on the layered silicates fragments surface. Moreover,
      the composites can be easily removed from water by a simple magnetic separation
      process.

PMID- 22608148
TI  - The effect of the spacer rigidity on the aggregation behavior of two ester
      containing Gemini surfactants.
AB  - Two Gemini surfactants with very similar structure but different spacer rigidity,
      namely 1-dodecanaminium,N,N'-[[(2E)-1,4-dioxo-2-butene-1,4-diyl]bis(oxy-2,1
      ethanediyl)]bis[N,N-dimethyl-,bromide] (12-fo-12) and 1-dodecanaminium, N,N'
      [(1,4-dioxo-1,4-butanediyl)bis(oxy-2,1-ethanediyl)] bis[N,N-dimethyl-, bromide]
      (12-su-12), and their monomeric counterpart 1-dodecanaminium, N-[2
      (acetyloxy)ethyl]-N,N-dimethyl-, bromide (DTAAB) were synthesized and their
      aggregation behavior in aqueous solutions was studied by measurements of surface
      tension, conductivity, isothermal titration calorimetry, dynamic light
      scattering, and transmission electron microscopy. It was found that the Krafft
      point of 12-fo-12 was 18.6 degrees C, significantly higher than that of 12-su-12
      (7.6 degrees C) and DTAAB (<0 degrees C). The minimum surface areas per
      surfactant A(min) at the water-air interface of DTAAB, 12-su-12, and 12-fo-12
      were determined. It was found that the value of A(min) of DTAAB was larger than
      half that of 12-su-12 but smaller than half that of 12-fo-12. The values of the
      degree of association beta of the three surfactants were found to be in a
      sequence of DTAAB>12-su-12>12-fo-12, which was in accord with the sequence of the
      entropy of micellization. The enthalpies of micellization of the two Gemini
      surfactants were found to be more negative than double that of DTAAB, and 12-fo
      12 had the most negative standard enthalpy of micellization. It was also found
      that 12-su-12 and DTAAB formed micelles in aqueous solutions, while 12-fo-12
      could form micelles and vesicles dependent on the concentration.

PMID- 22608149
TI  - Aggregation properties of supralong-chain surfactants with double or triple
      quaternary ammonium head groups.
AB  - Double or triple quaternary ammonium head groups were designed to improve the
      solubility of supralong alkyl chain surfactants. In the surfactant head group,
      quaternary ammonium groups are connected by an ethylene spacer. Micellar shapes
      of divalent surfactants [C(n)H(2n)(+1)N(+)(CH(3))(2)-(CH(2))(2)-N(+)(CH(3))(3)
      2Br(-): C(n)-2Am (n=18, 20, and 22)] and trivalent surfactants
      [C(n)H(2n)(+1)N(+)(CH(3))(2)-(CH(2))(2)-N(+)(CH(3))(2)-(CH(2))(2)-N(+)(CH(3))(3)
      3Br(-): C(n)-3Am (n=18, 20, and 22)] were studied in aqueous solutions by means
      of dynamic light scattering (DLS) and transmission electron microscopy (TEM).
      Changes in the surfactant concentration have a small influence on the apparent
      hydrodynamic radii (r(h)) of the molecular aggregates in both surfactant series.
      Average values of r(h) of aggregates are 60-90 nm for C(n)-2Am (n=18, 20, and 22)
      and 2-40 nm for C(n)-3Am (n=18, 20, and 22). TEM micrographs showed that
      aggregates of C(n)-2Am (n=18, 20, and 22) typically formed rod-like micelles. In
      contrast, trivalent surfactants of C(n)-3Am (n=18, 20, and 22) formed spherical
      (C(18)-3Am) or ellipsoidal micelles (C(20)-3Am and C(22)-3Am). Moreover, the
      degree of micellar counterion binding for these surfactants was determined by
      using a bromide ion-selective electrode, which indicated relatively high values
      (0.8-0.9) for C(n)-2Am (n=18, 20, and 22) and more common values (0.5-0.8) for
      C(n)-3Am (n=18, 20, and 22). The size of the aggregates is closely related to the
      degree of counterion binding.

PMID- 22608150
TI  - Study of hierarchical microstructures self-assembled by pi-shaped ABC block
      copolymers in dilute solution using self-consistent field theory.
AB  - Microstructures self-assembled by amphiphilic ABC pi-shaped block copolymers in
      dilute solution have been investigated by self-consistent field theory. The
      effects of architectural parameters and the interaction strength among the three
      blocks have been studied systematically. Our calculation results show that the
      distance of the two graft blocks has stronger effect than the length of graft
      blocks and the position of the first graft point on the phase behavior. The
      interaction strength among the three blocks is another important factor in
      controlling the resulting microstructures. Compound-core, multicompartment, and
      multicore micelles are observed in the case of pi-shaped ABC block copolymers
      with hydrophilic backbone block A and hydrophobic graft blocks B and C. Core
      shell-corona, incomplete skin-layered and hamburger micelles are formed when
      graft block C is hydrophilic and blocks A and B are hydrophobic. The wormlike
      multicore micelles have drawn our attention. We find that the morphology of
      wormlike multicore micelle can be controlled by changing the distance of the two
      graft blocks of the pi-shaped block copolymers. In all of the wormlike multicore
      micelles, the streamline wormlike micelle is more stable than other wormlike
      micelles from the free energy analysis.

PMID- 22608151
TI  - Fixed-bed column studies of pentachlorophenol removal by use of alginate
      encapsulated pillared clay microbeads.
AB  - Columns were packed with two alginate/pillared clays microbeads (aluminium
      pillared clay and surfactant-modified aluminium-pillared clay). Pentachlorophenol
      sorption performance was assessed under variable operating conditions: different
      bed heights, influent pentachlorophenol concentrations and flow rates. These
      conditions greatly influenced the breakthrough time/volume, the saturation
      time/volume and the uptake capacity. Higher values of experimental uptake
      capacities were obtained for the encapsulated surfactant-modified aluminium
      pillared clay compared with the encapsulated aluminium-pillared clay, and the
      values were compared with those obtained with other low-cost sorbents. The
      experimental breakthrough curves were modelled using Bed Depth Service Time
      (BDST), Wolborska and Thomas models. Linear relationship was obtained for the
      BDST model, indicating the suitability of this model; bed capacity increased
      sharply with the introduction of CTAB in the inorgano-pillared clay. Wolborska
      model was applied only to the initial part of the curves. Thomas model was no
      doubt the most suitable description of the adsorption mechanisms for the entire
      breakthrough curves. Experimental and Thomas model-predicted equilibrium uptake
      capacities were in accordance.

PMID- 22608152
TI  - The role of IMiDs alone or in combination in prostate cancer.
AB  - Recent insights into mechanisms by which prostate cancer becomes castration
      resistant have allowed better and more rational therapeutic design. These novel
      therapies have complemented the modest success that chemotherapy has shown in
      recent years changing the landscape of this disease and leading to improved
      outcomes. Angiogenesis and immune deregulation are 2 pathways that have
      increasingly been shown to lead into castration resistant prostate cancer (CRPC).
      Thalidmide and lenalidomide are immunomodulatory agents with antiangiogenesis
      properties that have shown activity in this setting with acceptable safety
      profile. In this review, we discuss briefly the different mechanisms that render
      prostate cancer castration resistant and elaborate on thalidomide and
      lenalidomide data in CRPC after reviewing their theoretic mechanisms of action.
      This timely review coincides with the identification of newer therapies against
      CRPC affirming our steady movement toward better disease control.

PMID- 22608153
TI  - Advocacy for tobacco control in India - a step forward.

PMID- 22608154
TI  - Longitudinal MRI study of the pituitary volume in chronic schizophrenia: a
      preliminary report.
AB  - This longitudinal MRI study investigated the pituitary volume in 17 patients with
      chronic schizophrenia and 17 matched controls. In contrast to previous findings
      of pituitary expansion during the first episode of schizophrenia, the chronic
      patients showed non-significant mild pituitary atrophy, suggesting that the
      pituitary volume changes differently at different illness stages.

PMID- 22608155
TI  - Excessive contralateral motor overflow in schizophrenia measured by fMRI.
AB  - Schizophrenia is characterized by significant problems in control of behavior;
      however, the disturbances in neural systems that control movement remain poorly
      characterized. We used functional magnetic resonance imaging (fMRI) to evaluate
      the origin of motor overflow in schizophrenia. Twenty-seven clinically stable
      medicated outpatients with Diagnostic and Statistical Manual, 4th edition, text
      revision (DSM-IV-TR)-defined schizophrenia (SZ), and 18 healthy control (HC)
      subjects, all right-handed, performed a dominant-handed, single-choice visual
      sensorimotor reaction time paradigm during fMRI. Voxel-wise analyses were
      conducted within sensorimotor cortical and striatal regions on general linear
      model (GLM)-derived measures of blood oxygen level-dependent (BOLD) signal
      change. The SZ group was not different from the HC group in reaction time,
      activation in somatosensory or motor cortices ipsilateral to the active
      (intended) descending corticospinal tract, nor visual cortex. However, in the
      right hemisphere (contralateral to the active M1), the SZ group showed
      significantly higher activation in primary motor cortex and adjacent premotor and
      somatosensory cortices (right Brodmann areas (BA) 1 through 4, and 6), and
      significantly lower activation in bilateral basal ganglia. Right BA 4 activation
      was strongly related to disorganization and poverty symptoms (and unrelated to
      medications) in the patient group. This study provides evidence in SZ of
      excessive neural activity in motor cortex contralateral to the intended primary
      motor cortex, which may form the basis for altered motor laterality and motor
      overflow previously observed, and disorganized behavior. This pathological motor
      overflow may be partly due to altered modulation of intended movement within the
      basal ganglia and premotor cortex.

PMID- 22608156
TI  - Cognitive and volumetric predictors of response to repetitive transcranial
      magnetic stimulation (rTMS) - a prospective follow-up study.
AB  - As the prevalence of treatment resistant depression (TRD) continues to rise, it
      remains a clinically important issue to identify neurobiological-, patient- and
      treatment-related factors that could potentially predict response to treatment.
      Medial temporal lobe (MTL) structures, in particular the hippocampus and amygdala
      have been implicated in inferior treatment response. The role of related
      structures such as the entorhinal cortex and the impact of MTL abnormalities on
      neurocognitive function, however, have not been systematically examined. The
      current study investigated MTL abnormalities and neurocognitive characteristics
      of eventual treatment responders and non-responders to a course of repetitive
      transcranial magnetic stimulation (rTMS) in order to identify potential
      predictors of treatment outcome. Prior to rTMS treatment all patients underwent
      magnetic resonance imaging (MRI) and neuropsychological assessment. MRI analysis
      was conducted using FreeSurfer 5.0. There was a 50% response rate following up to
      a 6-week course of daily rTMS treatments. Treatment response was defined as 50%
      reduction in Hamilton Depression Rating Scale and BDI-II scores from baseline.
      There was no difference in pre-treatment neurocognitive profiles and MTL volumes
      between eventual treatment responders and non-responders. Smaller pre-treatment
      left hippocampus volume showed a trend towards predicting eventual subjective
      improvement in depressive symptomatology. Although preliminary, our findings
      suggest that structural abnormalities may have some potential for predicting
      outcome to rTMS.

PMID- 22608158
TI  - An edge-region force guided active shape approach for automatic lung field
      detection in chest radiographs.
AB  - Automatic and accurate lung field segmentation is an essential step for
      developing an automated computer-aided diagnosis system for chest radiographs.
      Although active shape model (ASM) has been useful in many medical imaging
      applications, lung field segmentation remains a challenge due to the superimposed
      anatomical structures. We propose an automatic lung field segmentation technique
      to address the inadequacy of ASM in lung field extraction. Experimental results
      using both normal and abnormal chest radiographs show that the proposed technique
      provides better performance and can achieve 3-6% improvement on accuracy,
      sensitivity and specificity compared to traditional ASM techniques.

PMID- 22608159
TI  - Association between urine cotinine levels, continuous performance test variables,
      and attention deficit hyperactivity disorder and learning disability symptoms in
      school-aged children.
AB  - BACKGROUND: We examined the cross-sectional relationship between environmental
      tobacco smoke exposure, continuous performance test (CPT) measures, and attention
      deficit hyperactivity disorder (ADHD) or learning disability symptoms in school
      aged children. METHOD: In total, 989 children (526 boys, mean age 9.1 +/- 0.7
      years), recruited from five South Korean cities participated in this study. We
      used urine cotinine as a biomarker for environmental tobacco smoke exposure, and
      obtained the children's scores on a CPT. Parents completed the Korean versions of
      the ADHD rating scale-IV (ADHD-RS) and learning disability evaluation scale
      (LDES). Using generalized linear mixed model (GLMM), we assessed the associations
      between urine cotinine concentrations, neuropsychological variables, and symptoms
      of ADHD and learning disabilities. Additionally, we conducted structural equation
      models to explore the effects' pathways. RESULTS: After adjusting for a range of
      relevant covariates, GLMM showed urinary cotinine levels were significantly and
      positively associated with CPT scores on omission errors, commission errors,
      response time, and response time variability, and with parent- and teacher-rated
      ADHD-RS scores. In addition, urine cotinine levels were negatively associated
      with LDES scores on spelling and mathematical calculations. The structural
      equation model revealed that CPT variables mediated the association between urine
      cotinine levels and parental reports of symptoms of ADHD and learning
      disabilities. CONCLUSIONS: Our data indicate that environmental exposure to
      tobacco smoke is associated with ADHD and learning disabilities in children, and
      that impairments in attention and inhibitory control probably mediate the effect.

PMID- 22608157
TI  - Functional interactions of HIV-infection and methamphetamine dependence during
      motor programming.
AB  - Methamphetamine (METH) dependence is frequently comorbid with HIV infection and
      both have been linked to alterations of brain structure and function. In a
      previous study, we showed that the brain volume loss characteristic of HIV
      infection contrasts with METH-related volume increases in striatum and parietal
      cortex, suggesting distinct neurobiological responses to HIV and METH (Jernigan
      et al., 2005). Functional magnetic resonance imaging (fMRI) has the potential to
      reveal functional interactions between the effects of HIV and METH. In the
      present study, 50 participants were studied in four groups: an HIV+ group, a
      recently METH-dependent group, a dually affected group, and a group of unaffected
      community comparison subjects. An fMRI paradigm consisting of motor sequencing
      tasks of varying levels of complexity was administered to examine blood
      oxygenation level dependent (BOLD) changes. Within all groups, activity increased
      significantly with increasing task complexity in large clusters within
      sensorimotor and parietal cortex, basal ganglia, cerebellum, and cingulate. The
      task complexity effect was regressed on HIV status, METH status, and the HIV*METH
      interaction term in a simultaneous multiple regression. HIV was associated with
      less complexity-related activation in striatum, whereas METH was associated with
      less complexity-related activation in parietal regions. Significant interaction
      effects were observed in both cortical and subcortical regions; and, contrary to
      expectations, the complexity-related activation was less aberrant in dually
      affected than in single risk participants, in spite of comparable levels of
      neurocognitive impairment among the clinical groups. Thus, HIV and METH
      dependence, perhaps through their effects on dopaminergic systems, may have
      opposing functional effects on neural circuits involved in motor programming.

PMID- 22608160
TI  - Does primary androgen-deprivation therapy delay the receipt of secondary cancer
      therapy for localized prostate cancer?
AB  - BACKGROUND: Despite evidence that shows no survival advantage, many older
      patients receive primary androgen-deprivation therapy (PADT) shortly after the
      diagnosis of localized prostate cancer (PCa). OBJECTIVE: This study evaluates
      whether the early use of PADT affects the subsequent receipt of additional
      palliative cancer treatments such as chemotherapy, palliative radiation therapy,
      or intervention for spinal cord compression or bladder outlet obstruction.
      DESIGN, SETTING, AND PARTICIPANTS: This longitudinal population-based cohort
      study consists of Medicare patients aged >= 66 yr diagnosed with localized PCa
      from 1992 to 2006 in areas covered by the Surveillance Epidemiology and End
      Results (SEER) program. SEER-Medicare linked data through 2009 were used to
      identify the use of PADT and palliative cancer therapy. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: Instrumental variable analysis methods were used to
      minimize confounding effects. Confidence intervals were derived from the
      bootstrap estimates. RESULTS AND LIMITATIONS: This study includes 29 775 men who
      did not receive local therapy for T1-T2 PCa within the first year of cancer
      diagnosis. Among low-risk patients (Gleason score 2-7 in 1992-2002 and Gleason
      score 2-6 in 2003-2006) with a median age of 78 yr and a median follow-up of 10.3
      yr, PADT was associated with a 25% higher use of chemotherapy (hazard ratio [HR]:
      1.25; 95% confidence interval [CI], 1.08-1.44) and a borderline higher use of any
      palliative cancer treatment (HR: 1.07; 95% CI, 0.97-1.19) within 10 yr of
      diagnosis in regions with high PADT use compared with regions with low PADT use.
      Because this study was limited to men >65 yr, the results may not be applicable
      to younger patients. CONCLUSIONS: Early treatment of low-risk, localized PCa with
      PADT does not delay the receipt of subsequent palliative therapies and is
      associated with an increased use of chemotherapy.

PMID- 22608161
TI  - Intrafamilial circulation of Tropheryma whipplei, France.
AB  - Tropheryma whipplei, which causes Whipple disease, has been detected in 4% of
      fecal samples from the general adult population of France. To identify T.
      whipplei within families, we conducted serologic and molecular studies, including
      genotyping, on saliva, feces, and serum from 74 relatives of 13 patients with
      classic Whipple disease, 5 with localized chronic T. whipplei infection, and 3
      carriers. Seroprevalence was determined by Western blot and compared with 300
      persons from the general population. We detected T. whipplei in 24 (38%) of 64
      fecal samples and 7 (10%) of 70 saliva samples from relatives but found no
      difference between persons related by genetics and marriage. The same circulating
      genotype occurred significantly more often in families than in other persons.
      Seroprevalence was higher among relatives (23 [77%] of 30) than in the general
      population (143 [48%] of 300). The high prevalence of T. whipplei within families
      suggests intrafamilial circulation.

PMID- 22608162
TI  - The interaction of various liquids with long-term denture soft lining materials.
AB  - OBJECTIVES: To study the uptake of liquids, representative of those encountered
      orally, by long-term denture soft lining materials, and analyze the data in terms
      of appropriate theories. METHODS: Four proprietary and one experimental soft
      lining material were investigated, and the weight change presented as a function
      of time in both aqueous and organic fluids over the course of a year. A separate
      experiment determined the equilibrium swelling in ethanol of poly(ethyl
      methacrylate) and poly(methyl methacrylate). RESULTS: Uptake date for the five
      soft lining materials in various aqueous solution, coconut oil and HB307 are
      reported. The experimental value for the equilibrium swelling of poly(ethyl
      methacrylate) and poly(methyl methacrylate) in ethanol was reported to indicate
      the solubility parameter of the system. SIGNIFICANCE: The results have been
      analyzed by relevant theoretical models, which have been shown to explain the
      experimental data.

PMID- 22608163
TI  - Wear behavior of dental Y-TZP ceramic against natural enamel after different
      finishing procedures.
AB  - OBJECTIVE: The aim of this in vitro study was to evaluate the influence of
      different finishing procedures on the wear behavior of zirconia against natural
      enamel. METHODS: 64 quadratic specimens (10 mm * 10 mm * 2 mm) were cut from a
      commercial hipped dental Y-TZP ceramic. Four different groups with 16 specimens
      each were formed according to the following finishing procedures: PZ (polished),
      RR (fine-grit diamond), GR (coarse-grit diamond), GZ (glazed). Polished specimens
      of a leucite-reinforced glass ceramic (Empress CAD) were used as a control (GC).
      The materials were subjected to the Ivoclar wear method (Willytec chewing
      simulator, 120,000 cycles, 5kg weight) with 80 natural caries-free cusps of first
      upper molars as antagonists. Wear was analyzed for both the enamel cusps and test
      specimens by measurement of the vertical substance loss with a laser scanner.
      Surface roughness was measured by means of a white-light interferometer. RESULTS:
      The surface roughness was significantly different among the polished, diamond
      finished, and glazed ceramic specimens (ANOVA, post hoc Bonferroni p<0.05). The
      results of the one-way ANOVA indicated that the finishing technique significantly
      affected enamel wear (p<0.05). The post hoc test indicated that the specimens
      finished with the coarse diamond caused significantly higher antagonist wear than
      the polished ones. Polished zirconia showed the lowest wear of the antagonist
      enamel, with a mean value of 171.74 (SD = 121.68), and resulted in enamel wear
      that was not significantly different from that of the glass ceramic control
      group. No significant linear correlation could be found between pre-testing
      surface roughness and abrasive wear. SIGNIFICANCE: If zirconia is used without
      veneering material for crowns and fixed dental prostheses (FDPs), the surface
      must be well-polished if occlusal adjustments with coarse diamonds are performed.
      The polishing step reduces the wear of the opposing enamel.

PMID- 22608164
TI  - Recognition and diagnosis of Cryptococcus gattii infections in the United States.

PMID- 22608165
TI  - Influence of pH and carbon to nitrogen ratio on mycotoxin production by
      Alternaria alternata in submerged cultivation.
AB  - Production of the Alternaria mycotoxins alternariol (AOH), alternariol
      monomethylether (AME) and tenuazonic acid (TA) by Alternaria alternata DSM 12633
      was influenced by pH and carbon to nitrogen (C:N) ratio of the growth medium both
      in shaking flasks and bioreactor cultivation. The impact of medium pH on
      mycotoxin production was studied in the range of pH 3.5 - 8. pH values above 5.5
      led to a decreased mycotoxin production or inhibited mycotoxin formation
      completely whereas an acidic pH in the range of 4.0-4.5 was optimal for mycotoxin
      production. The influence of the C:N ratio was evaluated over the range of 24 to
      96. Glucose was used as carbon source and its concentration was altered while
      nitrogen concentration was kept constant. Growth kinetics and mycotoxin
      production parameters were studied depending on different C:N ratios. With
      increasing initial glucose concentration fungal biomass did increase but the
      maximum specific growth rate was not influenced. The optimal initial C:N ratio
      for attaining highest mycotoxin concentrations was 72. A higher C:N ratio did not
      further enhance mycotoxin production.

PMID- 22608166
TI  - Neuroendocrine and mucinous differentiation in signet ring cell carcinoma of the
      stomach: evidence for a common cell of origin in composite tumors.

PMID- 22608167
TI  - CD5(-) diffuse large B-cell lymphoma with peculiar cyclin D1+ phenotype.
      Pathologic and molecular characterization of a single case.

PMID- 22608168
TI  - Effect of subtalar arthroereisis on the tibiotalar contact characteristics in a
      cadaveric flatfoot model.
AB  - Previous studies reported the effect of flatfoot deformity on tibiotalar joint
      contact characteristics. The lateral shift of the load which occurred in flatfeet
      may be responsible for degenerative changes in the ankle joint. The purpose was
      to assess the pattern of joint contact stress of the tibiotalar joint in intact,
      flat, and corrected specimens with subtalar arthroereisis. Seven fresh-frozen
      cadaver specimens were studied in the intact and flat-footed condition after
      transection of ligaments which support the medial arch. Ankle joint contact
      stress and plantar pressure patterns were determined from a capacitive pressure
      sensor inserted in the tibiotalar joint and a pressure distribution platform when
      the specimens were axially loaded in simulated mid-stance. Contact pressure was
      also assessed after subtalar arthroereisis with a 12 mm Kalix implant for
      correction of the flatfoot deformity. A maximum contact pressure of 1414.2+/
      319.2 kPa was recorded in the middle-medial region in intact specimens. Flatfoot
      caused a lateral shift in the pressure distribution (p<0.05). In the flat
      specimens, the maximum contact pressure of 1394.7 8+/-470.5 kPa was in the
      anterior-central region. After subtalar arthroereisis with the Kalix implant for
      correction of the flatfoot deformity a maximum contact pressure of 1323.3+/-497.5
      kPa was observed in the middle-lateral region. In a cadaver model, subtalar
      arthroereisis with Kalix implant failed to restore a normal intraarticular ankle
      joint pressure pattern. Further interventions should be considered to restore a
      normal pressure pattern.

PMID- 22608169
TI  - Analysis of the air/water channels of gastrointestinal endoscopies as a risk
      factor for the transmission of microorganisms among patients.
AB  - BACKGROUND: For the effective reprocessing of gastrointestinal endoscopes,
      contaminants must be removed from the entire surface. However, these devices have
      long and narrow channels that can make this process difficult. METHODS: In this
      cross-sectional study, the staff assigned to reprocess gastroscopes and
      colonoscopes in 37 services located throughout Brazil completed a questionnaire
      regarding reprocessing practices geared toward the channels in these devices. In
      addition, samples from these air/water channels were collected for
      microbiological analysis. RESULTS: Contamination was detected in 71.8% (28/39) of
      the samples obtained from the air/water channels of colonoscopes, and in 70%
      (42/60) of the samples from the air/water channels of gastroscopes. The median
      microbial load was 1,800 colony-forming units (CFU)/mL in the colonoscopes and
      750 CFU/mL in the gastroscopes. The main microorganisms isolated from the
      air/water channels of gastroscopes were Pseudomonas aeruginosa (26.4%),
      Escherichia coli (18.9%), and Acinetobacter baumannii (9.4%), and those isolated
      from the colonoscopes included P aeruginosa (46.4%), A baumannii (14.3%), and
      Klebsiella pneumoniae (10.7%), among others. The possible causes of the
      contamination of these devices included the failure to fill these channels with
      cleaning solution, lack of friction during cleansing, and inadequate rinsing.
      CONCLUSION: The contamination of the air/water channels did in fact represent a
      risk for the transmission of microorganisms during gastrointestinal endoscopy
      exams, possibly related to the inadequate reprocessing of these channels.

PMID- 22608170
TI  - What do physiotherapists consider to be the best sitting spinal posture?
AB  - While sitting is a common aggravating factor in low back pain (LBP), the best
      sitting posture remains unclear. This study investigated the perceptions of 295
      physiotherapists in four different European countries on sitting posture.
      Physiotherapists selected their perceived best sitting posture from a sample of
      nine options that ranged from slumped to upright sitting, as well as completing
      the back beliefs questionnaire (BBQ). 85% of physiotherapists selected one of two
      postures as best, with one posture being selected significantly more frequently
      than the remainder (p < 0.05). Interestingly, these two most frequently selected
      postures were very different from each other. Those who selected the more upright
      sitting posture had more negative LBP beliefs on the BBQ (p < 0.05). The choice
      of best sitting posture also varied between countries (p < 0.05). Overall,
      disagreement remains on what constitutes a neutral spine posture, and what is the
      best sitting posture. Qualitative comments indicated that sitting postures which
      matched the natural shape of the spine, and appeared comfortable and/or relaxed
      without excessive muscle tone were often deemed advantageous. Further research on
      the perceptions of people with LBP on sitting posture are indicated.

PMID- 22608171
TI  - Functional MMP-9 polymorphisms modulate plasma MMP-9 levels in multiple sclerosis
      patients.
AB  - We have described that MMP-9 C(-1562)T and (CA)(n) polymorphisms contribute to
      multiple sclerosis (MS). Here, we evaluate whether plasma MMP-9 levels are
      related to disease severity, drug therapy resistance and polymorphisms. For sub
      study 1, 36 patients with MS and 35 controls were recruited. For sub-study 2, 88
      individuals (53 patients and 35 controls) were included in a cross-sectional
      analysis. MS patients presented higher MMP-9 activity (1.4+/-0.18 versus 0.93+/
      0.18A.U. for control, P<0.05). Drug-therapy resistant individuals exhibited
      increased MMP-9 activity (1.96+/-0.25 versus 1.21+/-0.09A.U. for non-resistant
      patients). EDSS score was also related to MMP-9 levels. The CT+TT and HH
      genotypes had higher MMP-9 levels as compared to patients carrying the CC and LL.
      Drug therapy resistance, disease severity, MMP-9 plasma activity and
      polymorphisms are associated with MS.

PMID- 22608172
TI  - Predicting need for allogeneic transfusion after total knee arthroplasty.
AB  - Total knee arthroplasty (TKA) can lead to substantial blood loss. To avoid the
      high costs of autologous blood predonation programs and efficiently allocate
      limited blood resources, we sought to identify preoperative and intraoperative
      factors associated with allogeneic blood transfusion (AllTx) after primary TKA
      and, subsequently, develop a model to predict patients who will require AllTx. We
      analyzed 31 independent variables in 644 primary unilateral TKAs without
      autologous blood predonation for requirement of AllTx. Seventy-one procedures
      (11.0%) required AllTx. Age, comorbid anemia, preoperative hemoglobin
      concentration, and surgical time were significant predictors for requiring AllTx.
      When applied to an independent cohort, our model for predicting the need for
      AllTx after TKA was 90% sensitive and 52.5% specific.

PMID- 22608173
TI  - From the editor's perspective....: what is emotional intelligence?

PMID- 22608174
TI  - The prevalence of peripheral arterial disease (PAD) and PAD risk factors among
      different ethnic groups in the US population.
AB  - The National Health and Nutrition Examination Survey (NHANES) 2003-2004 data set
      was utilized to examine and compare trends and differences in PAD-related risk
      factor variables among 5 different ethnic/racial groups. The sample included
      individuals 40 years and older with PAD and of the ethnic/racial groups: Mexican
      American, Other Hispanic, Non-Hispanic White, Non-Hispanic Black, and
      Other/Multiracial. Two demographic variables (age and gender) and 4 PAD-risk
      factors (hypertension [HTN], systolic blood pressure [SBP], and diastolic blood
      pressure [DBP]), dyslipidemia, high-density lipoprotein [HDL] and low-density
      lipoprotein [LDL], diabetes, and cigarette smoking) were examined for each group.
      The study design conducted was descriptive using the NHANES 2003-2004 secondary
      data set. Raw data were weighted. Descriptive statistics were measured, Chi
      squares were compared, and Phi-coefficients were measured for association using
      SAS version 9.1 and SUDAAN 10.0. The group with the highest prevalence of PAD are
      females 40-50 years of age, and the ethnic group with PAD who have the highest
      risk for PAD-related risk factors are Non-Hispanic Black. Through Chi-square
      significant differences (P=0.00001-0.03874) between specific ethnic groups for
      all four PAD-related risk factors (i.e., HTN, dyslipidemia, diabetes and
      cigarette smoking). All of the associations between the prevalence of HTN,
      dyslipidemia, diabetes, or cigarette smoking and ethnicity were statistically
      significant (P=<0.0001). Overall differences exist among the different ethnic
      groups.

PMID- 22608175
TI  - Development and implementation of a standardized care plan for carotid
      endarterectomy.
AB  - Carotid endarterectomy (CEA) is a standardized surgical procedure and is the
      third most common vascular surgical procedure in Sweden. To improve the quality
      of pre- and postoperative care for patients undergoing elective CEA, a
      standardized care plan (SCP) was developed and implemented during Spring of 2007
      at a vascular clinic in Sweden. In order to spread light on obstacles and
      possibilities in the implementation-process of this procedure, the aim was to
      evaluate the development and implementation process of the standardized care plan
      for CEA. During the first ten months after the implementation of the SCP for CEA,
      a review of 83 SCPs was performed. Further, fifteen registered nurses and
      fourteen assistant nurses answered a questionnaire aimed at evaluating the use of
      standardized care plans. The review of the used SCP for CEA showed that three out
      of eighty-four patients had not been cared for in accordance to the SCP and that
      some of the documentation was redundant and unnecessary. All 29 nurses (100%)
      reported that they totally or partly agree with the Usability Items. Twenty-four
      of all nurses (82%) reported that their documentation was restricted by using the
      SCP; on the other hand, all nurses (100%) agreed that the documentation was easy,
      saved time, and decreased redundant information. The total sample reported high
      median scores in the areas of Quality of Care and Implementation (32.0,
      respectively 13.0), but sixteen nurses (59%) agreed that they mostly relied on
      their work experience and not the SCP. All nurses generally had a positive
      attitude towards SCP and felt that these procedures do facilitate their work and
      improve quality of care. The introduction of SCPs is one important way of
      implementing evidence-based knowledge and pursuing high quality work.

PMID- 22608176
TI  - Retrospective study of emerging themes in the decision-making process of patients
      considering amputation.
AB  - How patients make decisions about their future treatment has been sparsely study
      and with respect to limb amputation, a particularly difficult decision, not at
      all. An examination of this should furnish nurses vital knowledge about how
      patients come to the decision to give or refuse this consent. To reach as deep
      understanding as possible of how from the patients' point of view they reach the
      decision to consent to the amputation of a lower limb. The research was conducted
      in the qualitative method. Thirty lower-limb amputees (aged 32-88) took part in
      the study. In-depth interviews were held with the participants. The data were
      processed by means of content analysis. The main thematic categories identified
      were, in the chronological order of their appearance: 'The trail of torment
      leading to the decision to amputate', 'The turning point--taking the decision' "I
      just couldn't take any more pain" "We opt for life, we don't want to die". The
      more protracted and pain-filled the 'the trail of torment' the more mentally
      prepared patients were to give consent to amputation. Asked to look back on their
      choice, almost all interviewees had no regrets and even found virtues in it. The
      patients' decisions represented a mix of their grasp of the medical information
      supplied them by their doctors, their own personal values--opting for life
      prevailing over the desire for a whole body, and consideration for their family.
      The patients saw the decision-making process about amputation as a process of
      achieving consensus between themselves, their doctors and their family.

PMID- 22608177
TI  - The effect of obstructive sleep apnea on amputation site healing.
AB  - Obstructive sleep apnea (OSA) is an independent risk for hypertension, cerebral
      artery stenosis, stroke and hypercoagulability.(1) Our research objective was to
      assess whether sleep disordered breathing affects the peripheral circulation,
      decreases perfusion as measured by TcPO2 and decreases the odds that a partial
      foot amputation site will heal. We hypothesized that OSA would be an independent
      risk factor causing delayed healing of partial-foot amputations. We conducted a
      retrospective, observational study on a total of 307 patients who had TcPO2
      measurements and underwent partial-foot amputation. Twenty-five of these patients
      had OSA. In our study, patients with OSA had a 3.7-fold increase in odds of
      healing within 3 months in comparison with patients without OSA. Of note, 16
      patients (64%) with OSA were not treated with continuous positive airway pressure
      (CPAP) and healed within 3 months. Our results do not support our hypothesis that
      the presence of sleep apnea may impair healing of partial foot amputations.
      Further studies are needed to fully determine the effect of OSA and its treatment
      on TcPO2s and healing.

PMID- 22608178
TI  - Review of an article: Statin use and risk of diabetes mellitus in postmenopausal
      women in the Women's Initiative (2012). Culver AL, Ockene IS, Balasubramanian R,
      et al. (Arch Intern Med 2012;172(2):144-52).

PMID- 22608179
TI  - Abiotic and biotic factors associated with the presence of Anopheles arabiensis
      immatures and their abundance in naturally occurring and man-made aquatic
      habitats.
AB  - BACKGROUND: Anopheles arabiensis (Diptera: Culicidae) is a potential malaria
      vector commonly present at low altitudes in remote areas in Reunion Island.
      Little attention has been paid to the environmental conditions driving larval
      development and abundance patterns in potential habitats. Two field surveys were
      designed to determine whether factors that discriminate between aquatic habitats
      with and without An. arabiensis larvae also drive larval abundance, comparatively
      in man-made and naturally occurring habitats. METHODS: In an initial preliminary
      survey, a representative sample of aquatic habitats that would be amenable to an
      intensive long-term study were selected and divided into positive and negative
      sites based on the presence or absence of Anopheles arabiensis larvae.
      Subsequently, a second survey was prompted to gain a better understanding of
      biotic and abiotic drivers of larval abundance, comparatively in man-made and
      naturally occurring habitats in the two studied locations. In both surveys,
      weekly sampling was performed to record mosquito species composition and larval
      density within individual habitats, as well as in situ biological characteristics
      and physico-chemical properties. RESULTS: Whilst virtually any stagnant water
      body could be a potential breeding ground for An. arabiensis, habitats occupied
      by their immatures had different structural and biological characteristics when
      compared to those where larvae were absent. Larval occurrence seemed to be
      influenced by flow velocity, macrofauna diversity and predation pressure.
      Interestingly, the relative abundance of larvae in man-made habitats (average:
      0.55 larvae per dip, 95%CI [0.3-0.7]) was significantly lower than that recorded
      in naturally occurring ones (0.74, 95%CI [0.5-0.8]). Such differences may be
      accounted for in part by varying pressures that could be linked to a specific
      habitat. CONCLUSIONS: If the larval ecology of An. arabiensis is in general very
      complex and factors affecting breeding site productivity sometimes not easy to
      highlight, our results, however, highlight lower populations of An. arabiensis
      immatures compared to those reported in comparable studies conducted in the
      African continent. Overall, this low larval abundance, resulting from both
      abiotic and biotic factors, suggests that vector control measures targeting
      larval habitats are likely to be successful in Reunion, but these could be better
      implemented by taking environmental variability into account.

PMID- 22608180
TI  - Predicting leaf gravimetric water content from foliar reflectance across a range
      of plant species using continuous wavelet analysis.
AB  - Leaf water content is an important variable for understanding plant physiological
      properties. This study evaluates a spectral analysis approach, continuous wavelet
      analysis (CWA), for the spectroscopic estimation of leaf gravimetric water
      content (GWC, %) and determines robust spectral indicators of GWC across a wide
      range of plant species from different ecosystems. CWA is both applied to the Leaf
      Optical Properties Experiment (LOPEX) data set and a synthetic data set
      consisting of leaf reflectance spectra simulated using the leaf optical
      properties spectra (PROSPECT) model. The results for the two data sets, including
      wavelet feature selection and GWC prediction derived using those features, are
      compared to the results obtained from a previous study for leaf samples collected
      in the Republic of Panama (PANAMA), to assess the predictive capabilities and
      robustness of CWA across species. Furthermore, predictive models of GWC using
      wavelet features derived from PROSPECT simulations are examined to assess their
      applicability to measured data. The two measured data sets (LOPEX and PANAMA)
      reveal five common wavelet feature regions that correlate well with leaf GWC. All
      three data sets display common wavelet features in three wavelength regions that
      span 1732-1736 nm at scale 4, 1874-1878 nm at scale 6, and 1338-1341 nm at scale
      7 and produce accurate estimates of leaf GWC. This confirms the applicability of
      the wavelet-based methodology for estimating leaf GWC for leaves representative
      of various ecosystems. The PROSPECT-derived predictive models perform well on the
      LOPEX data set but are less successful on the PANAMA data set. The selection of
      high-scale and low-scale features emphasizes significant changes in both overall
      amplitude over broad spectral regions and local spectral shape over narrower
      regions in response to changes in leaf GWC. The wavelet-based spectral analysis
      tool adds a new dimension to the modeling of plant physiological properties with
      spectroscopy data.

PMID- 22608181
TI  - Changes in calf muscle deoxygenation after foam sclerotherapy in patients with
      superficial venous insufficiency.
AB  - OBJECTIVE: This study assessed changes in the calf muscle deoxygenated hemoglobin
      (HHb) level during light-intensity exercise after ultrasound-guided foam
      sclerotherapy (UGFS) for superficial venous insufficiency. METHODS: UGFS with 1%
      or 3% polidocanol foam (POL-F) was used to treat unilateral great saphenous vein
      reflux in 84 patients. Near-infrared spectroscopy (NIRS) was used to measure calf
      muscle HHb levels before and 3 months after UGFS. The calf venous HHb blood
      filling index was calculated on standing, the calf venous HHb ejection index was
      obtained after one tiptoe movement, and the venous HHb retention index was
      obtained after 10 tiptoe movements. The primary end point was an evident
      improvement in calf muscle deoxygenation after UGFS. The secondary end point was
      obliteration of the great saphenous vein. RESULTS: Treatment consisted of 1% POL
      F in 48 limbs and 3% POL-F in the remaining 36. Ultrasound imaging at the 3-month
      follow-up demonstrated complete occlusion in 56.3% of the patients who received
      injections of 1% POL-F and in 66.7% of those who received injections of 3% POL-F.
      The difference in treatment outcome between the groups was not significant
      (P=.333). Reflux was absent in 39 limbs (81.3%) treated with 1% POL-F and in 34
      limbs (94.4%) treated with 3% POL-F, and no significant difference was observed
      between the two groups (P=.076). Postsclerotherapy NIRS demonstrated significant
      reductions in the levels of the HHb filling index in both treatment groups
      (P=.039, P=.0001, respectively) and significant reductions in the levels of the
      HHb retention index (P<.0001, P=.008, respectively). However, the differences in
      the levels of the HHb ejection index before and after UGFS were not significant
      (P=.250, P=.084, respectively). CONCLUSIONS: Our present findings suggest that
      changes in the values of these parameters may be of potential use for assessing
      the effects of foam sclerotherapy in patients with superficial venous
      insufficiency.

PMID- 22608182
TI  - Wait times among patients with symptomatic carotid artery stenosis requiring
      carotid endarterectomy for stroke prevention.
AB  - BACKGROUND: Current Canadian and international guidelines suggest patients with
      transient ischemic attack (TIA) or nondisabling stroke and ipsilateral internal
      carotid artery stenosis of 50% to 99% should be offered carotid endarterectomy
      (CEA) <= 2 weeks of the incident TIA or stroke. The objective of the study was to
      identify whether these goals are being met and the factors that most influence
      wait times. METHODS: Patients who underwent CEA at the Ottawa Hospital for
      symptomatic carotid artery stenosis from 2008 to 2010 were identified. Time
      intervals based on the dates of initial symptoms, referral to and visit with a
      vascular surgeon, the decision to operate, and the date of surgery were recorded
      for each patient. The influence of various factors on wait times was explored,
      including age, sex, type of index event, referring physician, distance from the
      surgical center, degree of stenosis, and surgeon assigned. RESULTS: Of the 117
      patients who underwent CEA, 92 (78.6%) were symptomatic. The median time from
      onset of symptoms to surgery for all patients was 79 days (interquartile range
      [IQR], 34-161). The shortest wait times were observed in stroke patients (49
      [IQR, 27-81] days) and inpatient referrals (66 [IQR, 25-103] days). Only 7 of the
      92 symptomatic patients (8%) received care within the recommended 2 weeks. The
      median surgical wait time for all patients was 14 days (IQR, 8-25 days). In the
      multivariable analysis, significant predictors of longer wait times included
      retinal TIA (P = .003), outpatient referrals (P = .004), and distance from the
      center (P = .008). Patients who presented to the emergency department had the
      shortest delays in seeing a vascular surgeon and subsequently undergoing CEA (P <
      .0001). There was no difference between surgeons for wait times to be seen in the
      clinic; however, there were significant differences among surgeons once the
      decision was made to proceed with CEA. CONCLUSIONS: Our wait times for CEA
      currently do not fall within the recommended 2-week guideline nor does it appear
      feasible within the current system. Important factors contributing to delays
      include outpatient referrals, living farther from the hospital, and presenting
      with a retinal TIA (amaurosis fugax). Our findings also suggest better scheduling
      practices once a decision is made to operate can modestly improve overall and
      surgical wait times for CEA.

PMID- 22608183
TI  - Altered in-stent hemodynamics may cause erroneous upgrading of moderate carotid
      artery restenosis when evaluated by duplex ultrasound.
AB  - OBJECTIVE: To assess the influence of stent application on in-stent hemodynamics
      under standardized conditions. METHODS: Ovine common carotid arteries before and
      after stent (6 * 40 mm, sinus-Carotid-RXt, combined open-closed cell design;
      Optimed, Ettlingen, Germany) application were used. Plastic tubes, 10 mm in
      length, simulating stenosis were placed in the middle of the applied stent to
      induce different degrees of stenosis (moderate 57.8% and severe 76.4%). Flow
      velocity and dynamic compliance were, respectively, measured with ultrasound and
      laser scan; proximal, in-stent, and distal to the stented arterial segment (1 cm
      proximal and distal) in a pulsatile ex vivo circulation system. RESULTS: Stent
      insertion caused the in-stent peak systolic velocity to increase 22% without
      stenosis, 31% with moderate stenosis, and 23% with severe stenosis. Stent
      insertion without stenosis caused no significant increase in in-stent end
      diastolic velocity (EDV) but a 17% increase with moderate stenosis. In severe
      stenosis, EDV was increased 56% proximal to the stenosis. Compliance was reduced
      threefold in the middle of the stented arterial segment where flow velocity was
      significantly increased. CONCLUSIONS: With or without stenosis, stent
      introduction caused the in-stent peak systolic velocity to become significantly
      elevated compared with a nonstented area. EDV was also increased by stent
      insertion in the case of moderate stenosis. The stent-induced compliance
      reduction may be causal for the increase in flow velocity since the stent-induced
      flow velocity elevation appeared in the stented area with low compliance. Because
      of altered hemodynamics caused by stent introduction when measured by duplex
      ultrasound, caution is prudent in concluding that carotid artery stenting is
      associated with a higher restenosis rate than carotid endarterectomy. Mistakenly
      upgrading moderate to severe restenosis could result in unnecessary
      reintervention. CLINICAL RELEVANCE: Clinical experience and prior studies support
      the supposition that restenosis after carotid artery stenting in carotid lesions
      displays erroneously elevated velocity when evaluated by duplex ultrasound (DUS),
      thus contributing to misleading interpretation of the degree of stenosis. This
      study, in contrast to studies of other groups, employs exactly the same
      conditions to measure flow with DUS in an unstented and then stented section of
      the carotid artery. Since DUS is the first-choice tool for carotid artery
      evaluation, knowledge about inexactness of the method is essential to avoid
      errors in treatment or follow-up decisions.

PMID- 22608184
TI  - Intestinal dysmotility and enteric neurochemical changes in a Parkinson's disease
      rat model.
AB  - Gastrointestinal disorders, constipation in particular, are the most common non
      motor dysfunctions affecting Parkinson's disease (PD) patients. We have
      previously reported that rats bearing unilateral nigrostriatal lesion caused by 6
      hydroxydopamine (6-OHDA) stereotaxic injection develop severe constipation
      together with a region-specific decrease of neuronal nitric oxide synthase (nNOS)
      in enteric neurons of the lower intestinal tract. Here, we extend these
      observations on other enteric neuronal subpopulations, investigating also the
      propulsive activity of isolated colonic specimens. Four weeks post 6-OHDA
      injection, lesioned rats showed a significant increase of vasoactive intestinal
      polypeptide (VIP) concomitant with the reduced expression of nNOS in the
      myenteric plexus of distal ileum and proximal colon; in particular VIP increased
      in a subpopulation of neurons actively expressing nNOS. On the other hand,
      choline acetyltransferase (ChAT) was not modified in any of the intestinal
      segments analyzed. Interestingly, we found a reduced expression of dopamine
      receptor type 2 (D2R) in proximal (-66.8%) and distal (-54.5%) colon, together
      with reduced peristalsis efficiency (decrease in intraluminal pressure and
      frequency of peristaltic events) in the 6-OHDA-lesioned rats. The selective
      depletion of dopaminergic nigrostriatal neurons is associated with changes in the
      expression of enteric inhibitory neurotransmitters, as well as of the D2R in
      intestinal specific regions. Moreover, 6-OHDA-lesioned rats demonstrated altered
      colon propulsive activity referable to the D2R decrease. Our findings unveil
      subtle mechanisms underlying the enteric neurochemical plasticity events evoked
      by disruption of the normal brain-gut cross-talk, giving a peculiar point of view
      on the pathophysiology of the severe constipation that frequently affects PD
      patients.

PMID- 22608185
TI  - [Radiologia: we've come a long way but we're not there yet].

PMID- 22608186
TI  - Hemoglobin level significantly impacts the tumor cell survival fraction in humans
      after internal radiotherapy.
AB  - BACKGROUND: Anemia is usually not taken into account in internal radiotherapy. We
      investigated whether the hemoglobin (Hb) level could have an impact on the tumor
      response, as observed in external beam radiotherapy (EBRT). METHODS: Absorbed
      doses of 25 hepatic metastatic sites in eight patients who underwent a liver
      selective internal radiotherapy (SIRT) were computed by a 3D convolution of a
      dose deposition kernel with the 90Y time-of-flight positron emission tomography
      (TOF-PET) images acquired following therapy. Early tumor response was assessed by
      comparing a follow-up FDG TOF-PET scan with a baseline scan. Hb level was
      measured on the day of the SIRT procedure. RESULTS: All patients displayed early
      tumor response increasing with the tumor-absorbed dose. Significant differences
      between patients were noted, the response slope correlating with the Hb level.
      After applying a global fit on all metastases using a tumor radiosensitivity
      modulated by a Hb enhancement factor (HEF) linearly dependent on the Hb level, a
      strong correlation (R = 0.96) was observed between the early response and the
      absorbed dose. Hb level had a major impact on tumor response by modulating HEF by
      a factor 6. CONCLUSIONS: These results prove the significant impact of Hb level
      on the tumor response and support the study of methods for correcting tumor
      hypoxia, such as intensively performed in EBRT. The quantitative analysis of the
      relationship between tumor doses and early response has the power to allow fast
      screening of such correction methods in limited patient series. Internal
      radiotherapy could be more efficient if performed earlier in the therapy line,
      when the disease- and treatment-related anemia remains limited.

PMID- 22608187
TI  - Water Safety Plan on cruise ships: a promising tool to prevent waterborne
      diseases.
AB  - BACKGROUND: Legionella spp. and other waterborne pathogens have been isolated
      from various water systems on land based premises as well as on ships and cases
      of Legionnaires' disease have been associated with both sites. Peculiarities of
      cruise ships water systems make the risk management a challenging process. The
      World Health Organization suggests a Water Safety Plan (WSP) as the best approach
      to mitigate risks and hazards such as Legionella spp. and others. OBJECTIVES: To
      develop WSP on a cruise ship and discuss challenges, perspectives and key issues
      to success. METHODS: Hazards and hazardous events were identified and risk
      assessment was conducted of the ship water system. Ship company management,
      policies and procedures were reviewed, site visits were conducted, findings and
      observations were recorded and discussed with engineers and key crew members were
      interviewed. RESULTS: A total of 53 hazards and hazardous events were taken into
      consideration for the risk assessment and additional essential barriers were
      established when needed. Most of them concerned control measures for biofilm
      development and Legionella spp. contamination. A total of 29 operational limits
      were defined. Supplementary verification and supportive programs were
      established. CONCLUSIONS: Application of the WSP to ship water systems, including
      potable water, recreational water facilities and decorative water features and
      fountains, is expected to improve water management on ships. The success of a WSP
      depends on support from senior management, commitment of the Captain and crew
      members, correct execution of all steps of a risk assessment and practicality and
      applicability in routine operation. The WSP provides to shipping industry a new
      approach and a move toward evidence based water safety policy.

PMID- 22608188
TI  - Resistance to asbestos-induced apoptosis with continuous exposure to crocidolite
      on a human T cell.
AB  - We have been investigating the immunological effects of asbestos. The
      establishment of a low-dose and continuously exposed human T cell line, HTLV-1
      immortalized MT-2, to chrysotile (CB) revealed reduction of CXCR3 chemokine
      receptor and production of IFN-gamma that caused a decline of tumor immunity.
      These effects were coupled with upregulation of IL-10, TGF-beta, and BCL-2 in
      asbestos-exposed patients. To observe the immunological effects of crocidolite
      (CR) on human T cells, a trial to establish a low-dose and continuously exposed
      model was conducted and compared with a previously reported CB-exposed model (MT
      2CB). Transient exposure of MT-2 original cells to CB or CR induced a similar
      level of apoptosis and growth inhibition. The establishment of a continuously
      exposed subline to CR (MT-2CR) revealed resistance against CR-induced apoptosis
      and upregulation of the BCL-2/BAX ratio similar to that recorded for MT-2CB. Both
      sublines showed reduced production of IFN-gamma, TNF-alpha, and IL-6 with
      increased IL-10. cDNA microarray with network/pathway analyses focusing on
      transcription factors revealed that many similar factors related to cell
      proliferation were involved following continuous exposure to asbestos in both MT
      2CB and MT-2CR. These results indicate that both CB and CR fibers affect human T
      cells with similar degrees even though the carcinogenic activity of these
      substances differs due to their chemical and physical forms. Trials to identify
      early detection markers for asbestos exposure or the occurrence of asbestos
      inducing malignancies using these findings may lead to the development of
      clinical tools for asbestos-related diseases and chemoprevention that modifies
      the reduced tumor immunity.

PMID- 22608189
TI  - Infants use different mechanisms to make small and large number ordinal
      judgments.
AB  - Previous research has shown indirectly that infants may use two different
      mechanisms--an object tracking system and an analog magnitude mechanism--to
      represent small (<4) and large (>=4) numbers of objects, respectively. The
      current study directly tested this hypothesis in an ordinal choice task by
      presenting 10- to 12-month-olds with a choice between different numbers of hidden
      food items. Infants reliably chose the larger amount when choosing between two
      exclusively small (1 vs. 2) or large (4 vs. 8) sets, but they performed at chance
      when one set was small and the other was large (2 vs. 4) even when the ratio
      between the sets was very favorable (2 vs. 8). The current findings support the
      two-mechanism hypothesis and, furthermore, suggest that the representations from
      the object tracking system and the analog magnitude mechanism are
      incommensurable.

PMID- 22608190
TI  - Anchoring in 4- to 6-year-old children relates to predictors of reading.
AB  - Previous studies suggest that anchoring, a short-term dynamic and implicit
      process that allows individuals to benefit from contextual information embedded
      in stimulus sequences, might be causally related to reading acquisition. Here we
      report findings from two experiments in which two previously untested predictions
      derived from this anchoring hypothesis were tested: (a) that anchoring
      facilitates rapid naming and phonological short-term memory in children prior to
      the onset of formal reading instruction and (b) that anchoring makes a unique
      contribution to performance in two early predictors of reading (letter knowledge
      and phonological awareness). In line with those predictions, naming times were
      faster and memory spans were longer under conditions that encouraged the use of
      anchoring processes than under conditions that afforded little anchoring.
      Furthermore, performance in the anchoring-affording condition predicted
      significant amounts of variance in phonological awareness and letter knowledge
      even after controlling for the contribution of the conditions that did not afford
      anchoring. Therefore, we suggest that anchoring might contribute to the
      development of reading-related processes during the preschool years independent
      of the development of specific reading-related skills such as phonological
      processing.

PMID- 22608191
TI  - [Factors associated to dropout of tuberculostatic treatment in the province of
      Granada].
AB  - OBJECTIVES: The factors associated to tuberculosis (TB) treatment drop-out can be
      very specific to the population and the local health care organization. We have
      studied the factors associated to TB treatment drop out in the province of
      Granada. SUBJECTS AND METHODS: A retrospective cohort study of TB cases
      registered in the province of Granada by the Epidemiological Surveillance System
      of Andalusia (SVEA) between 2003 and 2010 was carried out. Incidence was
      calculated in the native and foreign population. An univariate analysis was
      performed to describe the characteristics in both groups and a logistic
      regression model was used to identify factors associated to therapeutic
      abandonment. RESULTS: A decreasing trend in the incidence of TB was observed,
      (20.47 in 2007 to 11 cases per 100,000 inhabitants in 2010, respectively. Mean
      age of foreign patients was lower than that of the natives (30.8 years vs. 46.0
      years, P<.001). The former predominately lived in the Granada district, while the
      natives lived in the Metropolitan district. The percentage of patients who
      abandoned antituberculous treatment was 12.2%, this being somewhat higher in the
      foreign patients than the national ones (14% vs 10%; P=.062). Being male (OR:
      1.65; 95% CI: 1.04-2.60; P=.033), foreigner (OR: 1.72; 95% CI: 1.04-2.83;
      P=.032), resident in the North-east district (OR: 3.64; 95% CI: 1.76-7.52;
      P=.005) and/or having extrapulmonary TB (OR: 1.78; 95% CI: 1.06-3.00; P=.029)
      were associated significantly to therapeutic abandonment. CONCLUSIONS: The
      incidence of TB in the province of Granada has decreased to about 10 cases per
      100,000 inhabitants/year. The percentage of patients who abandon TB treatment is
      significant, it being higher in foreign patients than in the natives. TB
      treatment abandonment was associated to being a man, living in the North-east
      district of Granada and having extrapulmonary TB.

PMID- 22608192
TI  - [A clinical and epidemiological study of the Trypanosoma cruzi infected
      population in the north metropolitan area of Barcelona].
AB  - BACKGROUND: As an inevitable consequence of Latin American immigration to Europe,
      Spain and other European countries, it is necessary to confront the approach to
      cases of Chagas infection/disease for which, epidemiologically, there are more
      questions than answers. This study has aimed to describe all the Chagas-infected
      population in the north metropolitan area of Barcelona (406,000 inhabitants).
      PATIENTS AND METHODS: A prospective and multicentric study was performed in 3
      hospitals and 1 International Health Unit. It included all patients with
      Trypanosoma cruzi positive serology, regardless of the requesting reason.Results
      The 139 diagnosed cases represent an annual incidence of: a) 0.68/10,000
      inhabitants and, b) 73.2/10,000 immigrants coming from endemic zones. Of the
      patients, 80 (57.6%) had alterations in some complementary tests: cardiologic 62
      (44.6%), digestive 38 (27.3%) and 20 (14.4%) both. According to the Brazilian
      Consensus of Chagas cardiomyopathy, they were classified as: 0=84 (60.4%); a=40
      (28.7%); b1=4 (2.9%), b2=10 (7.2%) and c/d=1 (0.7%). Treatment with benznidazole
      (5mg/kg/24h for 60 days) was prescribed in 116 (83.4%) patients, 89 (76.7%) of
      whom completed it. Secondary effects were recorded in 56 (50.9%), which made it
      necessary to withdraw it in 21 (19.1%). CONCLUSIONS: Fewer cases of Chagas
      infection/disease than expected have been diagnosed in the North Metropolitan
      area of Barcelona. The series contains a high number of patients and there may be
      an elevated number of immigrants from endemic zones who have the asymptomatic
      chronic stages of the infection and who were unaware of their condition.

PMID- 22608193
TI  - Antiretroviral prophylaxis for HIV prevention reaches a key milestone.

PMID- 22608194
TI  - Bilateral axillary ectopic breast tissue.

PMID- 22608195
TI  - Human gyrovirus DNA in human blood, Italy.
AB  - Human gyrovirus (HGyV) is a recent addition to the list of agents found in
      humans. Prevalence, biologic properties, and clinical associations of this novel
      virus are still incompletely understood. We used qualitative PCRs to detect HGyV
      in blood samples of 301 persons from Italy. HGyV genome was detected in 3 of 100
      solid organ transplant recipients and in 1 HIV-infected person. The virus was not
      detected in plasma samples from healthy persons. Furthermore, during observation,
      persons for whom longitudinal plasma samples were obtained had transient and
      scattered presence of circulating HGyV. Sequencing of a 138-bp fragment showed
      nucleotide identity among all the HGyV isolates. These results show that HGyV can
      be present in the blood of infected persons. Additional studies are needed to
      investigate possible clinical implications.

PMID- 22608196
TI  - Coccidioidal endophthalmitis in immunocompetent person, California, USA.

PMID- 22608197
TI  - Intraoral curettage without presurgical endovascular embolization: a simple but
      controversial treatment of arteriovenous malformations of the mandible.
AB  - Arteriovenous malformation of the mandible is a rare and life-threatening lesion.
      The gold standard treatment is to extirpate the lesion surgically after
      endovascular embolization. Preoperative endovascular embolization is widely
      accepted, but there are limitations to the treatment. The authors introduce a
      technique in which the lesion is divided into parts and filled with bone wax,
      then curetted step by step. This gradual curettage method is effective and could
      be used instead of the standard treatment especially in hospitals with limited
      facilities for endovascular embolization.

PMID- 22608198
TI  - Coronoid process hyperplasia: a systematic review of the literature from 1995.
AB  - The objective of this study was to review the literature and compare different
      surgical methods for the management of coronoid process hyperplasia. A literature
      search was performed for publications since 1995. Case characteristics were
      extracted (age, sex, duration of symptoms, form, maximal mouth opening and
      treatment) and entered into a database for analysis. The data were split into two
      groups (coronoidectomy and coronoidotomy). Maximal mouth opening measurements
      before and after surgery were analyzed with several statistical tests. 61 cases
      were entered into the database. The mean age was 23 years and mean duration of
      symptoms 7 years. The bilateral form occurred 4.1 times more frequently than the
      unilateral form. The male-female ratio was 3.3 to 1. In 94% of the cases the
      approach was intra-oral. 84% of the cases received a coronoidectomy. Statistical
      analysis showed that the preoperative and postoperative differences between the
      groups were significant. The results were not significant when corrected for the
      preoperative difference. Postoperative therapy was not comparable due to
      heterogeneity. Cases that received a coronoidotomy had slightly better
      postoperative results.

PMID- 22608199
TI  - Early extraction: a silver bullet to avoid nerve injury in lower third molar
      removal?
AB  - This retrospective study evaluated the effects of early extraction of immature
      lower third molar on preventing complications, particularly nerve injury
      following lower third molar removal. Patients were grouped according to age and
      radiographic results: group A (518 patients, <=23 years, immature teeth with
      apical foramen not closed); group B (532 patients, >23 years, mature teeth with
      closed apical foramen). Group A included 230 males and 288 females (average age
      17 years). In group A, 808 lower mandibular third molars were extracted
      bilaterally in 290 and unilaterally in 228 patients; the incidence of
      complications was 2.48% (20/808) (all were temporary), the incidence of nerve
      injury was 0%. Group B included 250 males and 282 females (average age 39 years).
      In group B, 810 lower third molars were extracted bilaterally in 278 and
      unilaterally in 254 patients; the incidence of complications was 10% (81/810),
      the incidence of nerve injury was 1.6% (13/810). All complications were
      temporary, except two removals of permanent inferior alveolar nerve numbness (>6
      months). In this study, early removal of the lower third molar was effective in
      avoiding some postoperative complications, especially nerve injury. Early
      extraction of lower third molar in youngsters is recommended following a team
      consultation.

PMID- 22608200
TI  - Social anxiety disorder and shame cognitions in psychosis.
AB  - BACKGROUND: Social anxiety disorder (SAD) is surprisingly prevalent among people
      with psychosis and exerts significant impact on social disability. The processes
      that underlie its development remain unclear. The aim of this study was to
      investigate the relationship between shame cognitions arising from a stigmatizing
      psychosis illness and perceived loss of social status in co-morbid SAD in
      psychosis. METHOD: This was a cross-sectional study. A sample of individuals with
      SAD (with or without psychosis) was compared with a sample with psychosis only
      and healthy controls on shame proneness, shame cognitions linked to psychosis and
      perceived social status. RESULTS: Shame proneness (p < 0.01) and loss of social
      status (p < 0.01) were significantly elevated in those with SAD (with or without
      psychosis) compared to those with psychosis only and healthy controls.
      Individuals with psychosis and social anxiety expressed significantly greater
      levels of shame (p < 0.05), rejection (p < 0.01) and appraisals of entrapment (p
      < 0.01) linked to their diagnosis and associated stigma, compared to those
      without social anxiety. CONCLUSIONS: These findings suggest that shame cognitions
      arising from a stigmatizing illness play a significant role in social anxiety in
      psychosis. Psychological interventions could be enhanced by taking into
      consideration these idiosyncratic shame appraisals when addressing symptoms of
      social anxiety and associated distress in psychosis. Further investigation into
      the content of shame cognitions and their role in motivating concealment of the
      stigmatized identity of being 'ill' is needed.

PMID- 22608201
TI  - Spectroscopic studies on interactions between cholesterol-end capped polyethylene
      glycol and liposome.
AB  - In order to confirm that the cholesterol end groups of cholesterol-end capped
      polyethylene glycol really insert into the liposome bilayer and investigate how
      the incorporation affects the microenvironment of liposome bilayer, two kinds of
      molecular probes, namely Nile Red and pinacyanol chloride, were used. Their UV
      visible and fluorescence spectrum were recorded before and after the addition of
      the polymer. Shifts of the maximum absorbance (lambda(max)) of Nile Red show that
      the bilayer microenvironment around Nile Red is becoming more polar with
      increasing polymer concentration while shifts of lambda(max) of pinacyanol
      chloride indicate that the surrounding environment of pinacyanol chloride is
      becoming more apolar with addition of polymer. Effect of composition of liposome
      was also studied. With high ratio of dimethyldioctadecylammonium bromide (DODAB)
      fraction in liposome, lambda(max) of Nile Red is more easily affected by the
      addition of Chol-PEG-Chol while liposome with cholesterol shows relatively high
      stability to the addition of Chol-PEG-Chol.

PMID- 22608202
TI  - Serum amyloid A triggers the mosodium urate -mediated mature interleukin-1beta
      production from human synovial fibroblasts.
AB  - BACKGROUND: Monosodium urate (MSU) has been shown to promote inflammasome
      activation and interleukin-1beta (IL-1beta) secretion in monocyte/macrophages,
      but the cellular pathway and nod-like receptor family, pyrin domain containing 3
      (NLRP3) inflammasome activation in synovial tissues, remain elusive. In this
      study, we investigated the effects of MSU on synovial fibroblasts to elucidate
      the process of MSU-mediated synovial inflammation. METHODS: Human synovial
      fibroblasts were stimulated with MSU in the presence or absence of serum amyloid
      A (SAA). The cellular supernatants were analyzed by immunoblotting using anti-IL
      1beta or anti-caspase-1 antibodies. IL-1beta or NLRP3 mRNA expressions were
      analyzed by real-time PCR or reverse transcription-PCR (RT-PCR) method. RESULTS:
      Neither SAA nor MSU stimulation resulted in IL-1beta or interleukin-1alpha (IL
      1alpha) secretions and pro-IL-1beta processing in synovial fibroblasts. However,
      in SAA-primed synovial fibroblasts, MSU stimulation resulted in the activation of
      caspase-1 and production of active IL-1beta and IL-1alpha. The effect of SAA on
      IL-1beta induction was impaired in cells by silencing NLRP3 using siRNA or
      treating with caspase-1 inhibitor. In addition, SAA induced the secretion of
      cathepsin B and NLRP3 mRNA expression in synovial fibroblasts. CONCLUSIONS: Our
      data demonstrate that exposure of human synovial fibroblasts to SAA promotes MSU
      mediated caspase-1 activation and IL-1beta secretion in the absence of microbial
      stimulation. These findings provide insight into the molecular processes
      underlying the synovial inflammatory condition of gout.

PMID- 22608203
TI  - [Nasal intubation with fibre bronchoscopy in a patient with a very large thyroid
      goitre].

PMID- 22608204
TI  - Runner's knowledge of their foot type: do they really know?
AB  - BACKGROUND: The use of correct individually selected running shoes may reduce the
      incidence of running injuries. However, the runner needs to be aware of their
      foot anatomy to ensure the "correct" footwear is chosen. OBJECTIVES: The purpose
      of this study was to compare the individual runner's knowledge of their arch type
      to the arch index derived from a static footprint. METHODS: We examined 92
      recreational runners with a mean age of 35.4+/-11.4 (12-63) years. A
      questionnaire was used to investigate the knowledge of the runners about arch
      height and overpronation. A clinical examination was undertaken using defined
      criteria and the arch index was analysed using weight-bearing footprints.
      RESULTS: Forty-five runners (49%) identified their foot arch correctly. Eighteen
      of the 41 flat-arched runners (44%) identified their arch correctly. Twenty-four
      of the 48 normal-arched athletes (50%) identified their arch correctly. Three
      subjects with a high arch identified their arch correctly. Thirty-eight runners
      assessed themselves as overpronators; only four (11%) of these athletes were
      positively identified. Of the 34 athletes who did not categorize themselves as
      overpronators, four runners (12%) had clinical overpronation. CONCLUSION: The
      findings of this research suggest that runners possess poor knowledge of both
      their foot arch and dynamic pronation.

PMID- 22608205
TI  - Alterations of motor performance and brain cortex mitochondrial function during
      ethanol hangover.
AB  - Ethanol has been known to affect various behavioral parameters in experimental
      animals, even several hours after ethanol (EtOH) is absent from blood
      circulation, in the period known as hangover. The aim of this study was to assess
      the effects of acute ethanol hangover on motor performance in association with
      the brain cortex energetic metabolism. Evaluation of motor performance and brain
      cortex mitochondrial function during alcohol hangover was performed in mice 6
      hours after a high ethanol dose (hangover onset). Animals were injected i.p.
      either with saline (control group) or with ethanol (3.8 g/kg BW) (hangover
      group). Ethanol hangover group showed a bad motor performance compared with
      control animals (p < .05). Oxygen uptake in brain cortex mitochondria from
      hangover animals showed a 34% decrease in the respiratory control rate as
      compared with the control group. Mitochondrial complex activities were decreased
      being the complex I-III the less affected by the hangover condition; complex II
      III was markedly decreased by ethanol hangover showing 50% less activity than
      controls. Complex IV was 42% decreased as compared with control animals. Hydrogen
      peroxide production was 51% increased in brain cortex mitochondria from the
      hangover group, as compared with the control animals. Quantification of the
      mitochondrial transmembrane potential indicated that ethanol injected animals
      presented 17% less ability to maintain the polarized condition as compared with
      controls. These results indicate that a clear decrease in proton motive force
      occurs in brain cortex mitochondria during hangover conditions. We can conclude
      that a decreased motor performance observed in the hangover group of animals
      could be associated with brain cortex mitochondrial dysfunction and the resulting
      impairment of its energetic metabolism.

PMID- 22608206
TI  - Unique mutational profile associated with a loss of TDG expression in the rectal
      cancer of a patient with a constitutional PMS2 deficiency.
AB  - Cells with DNA repair defects have increased genomic instability and are more
      likely to acquire secondary mutations that bring about cellular transformation.
      We describe the frequency and spectrum of somatic mutations involving several
      tumor suppressor genes in the rectal carcinoma of a 13-year-old girl harboring
      biallelic, germline mutations in the DNA mismatch repair gene PMS2. Apart from
      microsatellite instability, the tumor DNA contained a number of C:G->T:A or G:C
      >A:T transitions in CpG dinucleotides, which often result through spontaneous
      deamination of cytosine or 5-methylcytosine. Four DNA glycosylases, UNG2, SMUG1,
      MBD4 and TDG, are involved in the repair of these deamination events. We
      identified a heterozygous missense mutation in TDG, which was associated with TDG
      protein loss in the tumor. The CpGs mutated in this patient's tumor are generally
      methylated in normal colonic mucosa. Thus, it is highly likely that loss of TDG
      contributed to the supermutator phenotype and that most of the point mutations
      were caused by deamination of 5-methylcytosine to thymine, which remained
      uncorrected owing to the TDG deficiency. This case provides the first in vivo
      evidence of the key role of TDG in protecting the human genome against the
      deleterious effects of 5-methylcytosine deamination.

PMID- 22608207
TI  - Clostridium difficile infection, Colorado and the northwestern United States,
      2007.
AB  - To determine the incidence of Clostridium difficile infection during 2007, we
      examined infection in adult inpatient and outpatient members of a managed-care
      organization. Incidence was 14.9 C. difficile infections per 10,000 patient
      years. Extrapolating this rate to US adults, we estimate that 284,875 C.
      difficile infections occurred during 2007.

PMID- 22608208
TI  - A review of chemical, electrochemical and biological methods for aqueous Cr(VI)
      reduction.
AB  - Hexavalent chromium is of particular environmental concern due to its toxicity
      and mobility and is challenging to remove from industrial wastewater. It is a
      strong oxidizing agent that is carcinogenic and mutagenic and diffuses quickly
      through soil and aquatic environments. It does not form insoluble compounds in
      aqueous solutions, so separation by precipitation is not feasible. While Cr(VI)
      oxyanions are very mobile and toxic in the environment, Cr(III) cations are not.
      Like many metal cations, Cr(III) forms insoluble precipitates. Thus, reducing
      Cr(VI) to Cr(III) simplifies its removal from effluent and also reduces its
      toxicity and mobility. In this review, we describe the environmental implications
      of Cr(VI) presence in aqueous solutions, the chemical species that could be
      present and then we describe the technologies available to efficiently reduce
      hexavalent chromium.

PMID- 22608209
TI  - Removal of lead by using Raschig rings manufactured with mixture of cement kiln
      dust, zeolite and bentonite.
AB  - The present investigation is a follow-up of study on manufacturing Raschig ring
      for removal of lead from aqueous solution. The mixtures were formulated using
      cement kiln dust, zeolite, and bentonite, normally used as natural adsorbents in
      the industrial scale, according to mixture design algorithm and response surface
      method. The pastes were prepared by addition of 28.0wt.% de-ionized water,
      containing 0.1wt.% carboxymethyl cellulose, with mixed powders. The adsorbents
      were fabricated by extrusion of the pastes in Raschig ring form and calcination
      at 500 degrees C after drying in oven. The effects of starting materials on the
      mechanical behavior of rings were studied from view point of mixture design
      algorithm to optimize the adsorbent composition. This method demonstrated to
      yield valuable information on the effects of used materials on mechanical
      characteristics. The study concluded that the strength, reliability and sorption
      capacity of ring can be simultaneously optimized by the addition of 47.5wt.%
      cement kiln dust, 32.5wt.% zeolite, and 20.0wt.% bentonite. In the next part of
      work, the sorption kinetics was investigated. The kinetic study indicated that
      the modified model can successfully correlate the sorption data. The equilibrium
      result showed the possibility of lead immobilization by fabricated rings.

PMID- 22608210
TI  - Periodontopathogens induce expression of CD40L on human platelets via TLR2 and
      TLR4.
AB  - INTRODUCTION: The outstanding importance of (soluble) CD40L to cardiovascular
      disease (CVD) is becoming increasingly apparent as CD40L is an important mediator
      of thrombotic and inflammatory processes. Platelets are the main source for CD40
      ligand, linking platelet stimulatory events to inflammation and adverse adaptive
      immune responses. Periodontitis represents a chronic dental infection by distinct
      gram negative bacteria that is associated with an increased risk for CVD.
      However, the effects of periodontopathogens on CD40L expression by platelets have
      not been determined. MATERIAL AND METHODS: Effects of periodontopathogens A.
      actinomycetemcomitans Y and P. gingivalis on the expression of CD40L were
      determined and the underlying receptors and pathways were investigated. 26
      patients with periodontitis and 19 controls were included in the clinical part of
      this study. RESULTS: Periodontopathogens directly induce surface expression of
      CD40L in human platelets. This activation depends on plasma factors like CD14 and
      involves TLR2 and TLR4 but not FcgammaRII. Inhibition of PI3K and PLC completely
      abolishes bacteria-induced surface expression of CD40L. TLR2 and TLR4 agonists,
      for example, are also able to induce expression and release of CD40L in human
      platelets. In patients with periodontitis, plasma levels of soluble CD40L are
      elevated and positivity for P. gingivalis is associated with a statistical
      significant increase of soluble CD40L. CONCLUSIONS: Our data indicate an
      involvement of periodontopathogens in increased plasma levels of soluble CD40L in
      periodontitis and therefore provide a novel link between periodontitis and
      increased risk for CVD.

PMID- 22608211
TI  - Residual platelets are the main determinants of microparticles count in frozen
      thawed plasma.

PMID- 22608212
TI  - Human MRSA isolates with novel genetic homolog, Germany.

PMID- 22608213
TI  - Chondrogenic differentiation of bone marrow-derived mesenchymal stem cells
      induced by acellular cartilage sheets.
AB  - Acellular cartilage sheets (ACSs) have been used as scaffolds for engineering
      cartilage with mature chondrocytes. In this study we investigated whether ACSs
      possess a chondrogenic induction activity that may benefit cartilage engineering
      with multipotent stem cells. Bone marrow-derived mesenchymal stem cells (BMSCs)
      isolated from newborn pigs were expanded in vitro and seeded on ACSs that were
      then stacked layer-by-layer to form BMSC-ACS constructs. Cells seeded on
      polyglycolic acid/polylactic acid (PGA/PLA) scaffolds served as a control. After
      4 weeks of culture with or without additional chondrogenic factors, constructs
      were subcutaneously implanted into nude mice for another 4 weeks. Cartilage-like
      tissues were formed after 4 weeks of culture. However, formation of cartilage
      with a typical lacunar structure was only observed in induced groups. RT-PCR
      showed that aggrecan, COMP, type II collagen and Sox9 were expressed in all
      groups except the non-induced BMSC-PGA/PLA group. At 4 weeks post-implantation,
      cartilage formation was achieved in the induced BMSC-ACS group and partial
      cartilage formation was achieved in the non-induced BMSC-ACS group, confirmed by
      safranin O staining, toluidine blue staining and type II collagen immunostaining.
      In addition, enzyme-linked immunosorbent assay demonstrated the presence of
      transforming growth factor-beta1, insulin-like growth factor-1 and bone
      morphogenic protein-2 in ACSs. These results indicate that ACSs possess a
      chondrogenic induction activity that promotes BMSC differentiation.

PMID- 22608214
TI  - Identification of anti-melanogenic natural compounds from Galega officinalis and
      further drug repositioning.

PMID- 22608215
TI  - New insights into therapy by mathematical analysis: recalcitrant granulated
      improved more than sclerotic venous leg ulcers with amelogenin treatment.
AB  - BACKGROUND: Chronic wounds are both time consuming as well as costly. A new
      therapeutic option for those wounds might be amelogenin, which supplies a
      temporary matrix to the fibroblasts and keratinocytes. OBJECTIVE: To prove the
      hypotheses for a divergent therapeutic outcome, we treated granulated vs.
      sclerotic chronic venous leg ulcers with amelogenin (Xelma(r)) 1*/week for 5-8
      weeks. METHODS: The analysis of the treatment was performed by applying a
      recently published mathematical model. This model can predict and evaluate
      different wound treatment methods by treating only few patients which is even
      more practicable for diseases with different influencing factors within patients
      groups because it is easier to collect only a small homogenous number of patients
      than multiple. RESULTS: We treated 12 granulated vs. 16 sclerotic ulcerations. 5
      (42%) of the granulated ulcerations with a mean initial wound area of 18.3cm(2)
      showed optimal wound healing (>90% epithelization). The average area of new
      epithelia was 11.9cm(2). Nine (56%) of the sclerotic ulcerations showed optimal
      wound healing with an initial wound area of 7.5cm(2) and a total average area of
      4.1cm(2) with new epithelia. For comparison of those groups, we extrapolate to a
      hypothetic mean sclerotic wound area of 18.3cm(2) analogue to the granulated
      ulcerations. This calculates to a mean neoepithel of only 6cm(2) for sclerotic
      ulcerations. Further on, we calculated about 2% of the wound area that
      proliferated in contrast to about 3% in granulated wounds. CONCLUSIONS: Although
      sclerotic ulcerations show higher growth rates, Xelma(r) seems to be more
      effective in granulated ulcerations. For larger sclerotic ulcerations the mean
      maximal covered wound area with neoepithelia is reduced to about 33% in contrast
      to 65% in granulated ulcerations.

PMID- 22608216
TI  - Attachment behaviour of Escherichia coli K12 and Salmonella Typhimurium P6 on
      food contact surfaces for food transportation.
AB  - The role of cargo container lining materials aluminium, a fibre reinforced
      plastic (FRP) and stainless steel in bacterial cross contamination during
      transport was assessed. For this, attachment and detachment of Escherichia coli
      K12 and Salmonella Typhimurium P6 on the three surfaces in the absence or
      presence of residues were evaluated. Observations were correlated with water
      contact angles of the materials (hydrophobicity) and roughness profile (R(a)).
      Attachment of the organisms was negatively correlated to the hydrophobicity of
      the three materials with r = -0.869 and -0.861 for E. coli K12 and S. Typhimurium
      P6 respectively. Correlation with roughness average was poor; r = -0.425 and 
      0.413 respectively for E. coli K12 and S. Typhimurium P6. Presence of residue
      caused significant reduction (p < 0.05) in the levels of bacteria attached to all
      materials, but made attached bacteria significantly more difficult to detach by
      either of two rinsing systems from all three surfaces. Explanation for these
      observations could be made in part from scanning electron micrographs which
      showed significantly more bacteria sitting on patches of residue when it was
      introduced to the surfaces, compared to the bare material sections of the same
      surfaces. We report these observations for the first time for aluminium and the
      FRP material and in part for stainless steel. The S. Typhimurium P6 strain also
      had significantly higher level of attachment than the E. coli K12 strain. Our
      findings show that food residue and soils affect the extent and amount of
      bacteria attaching to abiotic surfaces by altering the surface contact properties
      for the bacteria. Physicochemical properties like hydrophobicity appear to be a
      better basis for material selection for hygienic design of containers, than the
      traditional use of R(a).

PMID- 22608217
TI  - Bayesian inference for quantifying Listeria monocytogenes prevalence and
      concentration in minced pork meat from presence/absence microbiological testing.
AB  - The purpose of this work was to estimate the prevalence and concentration of
      Listeria monocytogenes in minced pork meat by the application of a Bayesian
      modeling approach. Samples (n = 100) collected from local markets were tested for
      L. monocytogenes using in parallel the PALCAM, ALOA and RAPID'L.mono selective
      media. Presence of the pathogen was confirmed through biochemical and molecular
      tests. Independent experiments (n = 10) for validation purposes were performed.
      No L. monocytogenes was enumerated by direct-plating (<10 CFU/g), though the
      pathogen was detected in 22% of the samples. Sensitivity and specificity varied
      depending on the culture method. L. monocytogenes concentration was estimated at
      14-17 CFU/kg. Validation showed good agreement between observed and predicted
      prevalence (error = -2.17%). The use of at least two culture media in parallel
      enhanced the efficiency of L. monocytogenes detection. Bayesian modeling may
      reduce the time needed to draw conclusions regarding L. monocytogenes presence
      and the uncertainty of the results obtained.

PMID- 22608218
TI  - Survey of raw milk cheeses for microbiological quality and prevalence of
      foodborne pathogens.
AB  - Cheese may be manufactured in the United States using raw milk, provided the
      cheese is aged for at least 60 days at temperatures not less than 35 degrees F
      (1.7 degrees C). There is now increased concern among regulators regarding the
      safety of raw milk cheese due to the potential ability of foodborne pathogens to
      survive the manufacturing and aging processes. In this study, 41 raw milk cheeses
      were obtained from retail specialty shops, farmers' markets, and on-line sources.
      The cheeses were then analyzed for the presence of Listeria monocytogenes,
      Salmonella, Escherichia coli O157:H7, Staphylococcus aureus, and Campylobacter.
      Aerobic plate counts (APC), coliform and yeast/mold counts were also performed.
      The results revealed that none of the enteric pathogens were detected in any of
      the samples tested. Five samples contained coliforms; two of those contained E.
      coli at less than 10(2) cfu/g. Three other cheese samples contained S. aureus.
      The APC and yeast-mold counts were within expected ranges. Based on the results
      obtained from these 41 raw milk cheeses, the 60-day aging rule for unpasteurized
      milk cheeses appears adequate for producing microbiologically safe products.

PMID- 22608219
TI  - Diversity of Saccharomyces cerevisiae yeasts associated to spontaneously
      fermenting grapes from an Italian "heroic vine-growing area".
AB  - The main aim of this work was to analyse the diversity of wild Saccharomyces
      cerevisiae isolated from spontaneous fermentations of grapes collected from
      heroic vine-growing area. A first screening based on several technological traits
      was used to select 39 strains among 132 isolates. By using three molecular typing
      techniques (evaluation of cell wall gene polymorphisms, mtDNA restriction
      analysis, inter-delta amplification analysis) a significant genetic variability
      was found. The analysis of principal aromatic compounds produced during
      inoculated fermentation of two grape musts demonstrated the strain impact on wine
      flavour and a significant influence of grape must on strain metabolic behavior.
      One selected strain was used in fermentation at cellar level and the analysis of
      inter-delta region on yeast colonies isolated during the process revealed the
      high-implantation ability of this strain. The obtained results demonstrate the
      usefulness of different molecular and technological markers for the evaluation of
      natural biodiversity among S. cerevisiae strains. This study represents an
      essential step towards the exploitation and the preservation of biodiversity of
      strains isolated from heroic vine-growing area. Selected S. cerevisiae strains
      could represent starter cultures available for winemakers addressed to production
      of quality premium wines maintaining differential properties of their own area.

PMID- 22608220
TI  - Antimicrobial activity of pediocin PA-1 against Oenococcus oeni and other wine
      bacteria.
AB  - Pediocin PA-1 is an antimicrobial peptide produced by lactic acid bacteria (LAB)
      that has been sufficiently well characterised to be used in food industry as a
      biopreservative. Sulphur dioxide is the traditional antimicrobial agent used
      during the winemaking process to control bacterial growth and wine spoilage. In
      this study, we describe the effect of pediocin PA-1 alone and in combination with
      sulphur dioxide and ethanol on the growth of a collection of 53 oenological LAB,
      18 acetic acid bacteria and 16 yeast strains; in addition, production of pediocin
      PA-1 by Pediococcus acidilactici J347-29 in presence of ethanol and grape must is
      also reported. Inhibitory concentrations (IC) and minimal bactericide
      concentrations of pediocin PA-1 were determined against LAB, and revealed a
      bacteriostatic effect. Oenococcus oeni resulted more sensitive to pediocin PA-1
      (IC(50) = 19 ng/ml) than the other LAB species (IC(50) = 312 ng/ml). Cooperative
      inhibitory effects of pediocin PA-1 and either sulphur dioxide or ethanol were
      observed on LAB growth. Moreover, the pediocin PA-1 producing P. acidilactici
      strain J347-29 was able to grow and produce the bacteriocin in presence of
      ethanol (up to 4% ethanol in the fermentation broth) and grape must (up to 80%),
      which indicated that pediocin PA-1 can be considered as a potential
      biopreservative in winemaking.

PMID- 22608221
TI  - Influence of serotype on the growth kinetics and the ability to form biofilms of
      Salmonella isolates from poultry.
AB  - The influence of the serotype on the growth behaviour and the ability to form
      biofilms of Salmonella enterica strains was investigated. The relationships
      between biofilm formation and growth kinetic parameters were also determined. A
      total of 69 strains (61 isolates from poultry and 8 reference strains from
      culture collections) belonging to 10 serotypes (S. enterica serotype Typhimurium,
      S. Newport, S. Paratyphi B, S. Poona, S. Derby, S. Infantis, S. Enteritidis, S.
      Virchow, S. Agona and S. Typhi) were tested. All Salmonella strains produced
      biofilms on polystyrene micro-well plates (crystal violet assay). Isolates were
      classified as weak (35 strains), moderate (22), or strong (12) biofilm producers.
      S. Agona and S. Typhi produced the most substantial (P < 0.001) biofilms. Growth
      curves were performed at 37  degrees C in tryptone soy broth by means of optical
      density (OD(420-580)) measurements from 0 to 48 h. Growth kinetic parameters
      (Gompertz model) varied between serotypes. The maximum growth rate (DeltaOD(420
      580)/h) ranged from 0.030 +/- 0.002 (S. Typhi) to 0.114 +/- 0.011 (S. Agona). The
      ability of Salmonella strains to form biofilms was not related to their growth
      kinetic parameters. The formation of biofilms by Salmonella on polystyrene
      constitutes an issue of concern because plastic materials are frequently used in
      food facilities. The findings suggest that special efforts must be made for the
      effective control of Salmonella in food-processing environments when S. Agona or
      S. Typhi strains are present.

PMID- 22608222
TI  - Evaluation of Fourier transform infrared (FT-IR) spectroscopy and chemometrics as
      a rapid approach for sub-typing Escherichia coli O157:H7 isolates.
AB  - The importance of tracking outbreaks of foodborne illness and the emergence of
      new virulent subtypes of foodborne pathogens have created the need for rapid and
      reliable sub-typing methods for Escherichia coli O157:H7. Fourier transform
      infrared (FT-IR) spectroscopy coupled with multivariate statistical analyses was
      used for sub-typing 30 strains of E. coli O157:H7 that had previously been typed
      by multilocus variable number tandem repeat analysis (MLVA) and pulsed field gel
      electrophoresis (PFGE). Hierarchical cluster analysis (HCA) and canonical variate
      analysis (CVA) of the FT-IR spectra resulted in the clustering of the same or
      similar MLVA types and separation of different MLVA types of E. coli O157:H7. The
      developed FT-IR method showed better discriminatory power than PFGE in sub-typing
      E. coli O157:H7. Results also indicated the spectral relatedness between
      different outbreak strains. However, the grouping of some strains was not in
      complete agreement with the clustering based on PFGE and MLVA. Additionally, HCA
      of the spectra differentiated the strains into 30 sub-clusters, indicating the
      high specificity and suitability of the method for strain level identification.
      Strains were also classified (97% correct) based on the type of Shiga toxin
      present using CVA of the spectra. This study demonstrated that FT-IR spectroscopy
      is suitable for rapid (<=16 h) and economical sub-typing of E. coli O157:H7 with
      comparable accuracy to MLVA typing. This is the first report of using an FT-IR
      based method for sub-typing E. coli O157:H7.

PMID- 22608223
TI  - Prevalence and characterization of antibiotic resistant Enterococcus faecalis in
      French cheeses.
AB  - Prevalence of enterococci and antibiotic resistance profiles of Enterococcus
      faecalis was analyzed in 126 French cheeses from retail stores. Forty-four
      percent of pasteurized or thermised-milk cheeses, and up to 92% of raw-milk
      cheeses contained detectable enterococci. A total of 337 antibiotic resistant
      enterococci were isolated in 29% and 60% of pasteurized-milk and raw-milk
      cheeses, respectively. E. faecalis was the predominant antibiotic resistant
      species recovered (81%), followed by Enterococcus faecium (13%), and Enterococcus
      durans (6%). The most prevalent antibiotic resistances were tetracycline (Tet)
      and minocycline (Min), followed by erythromycin (Ery), kanamycin (Kan) and
      chloramphenicol (Cm). The most common multiple antibiotic resistance phenotype
      was Cm Ery Kan Min Tet. The occurrence of antibiotic genes, as searched by PCR,
      was 100 % for aph3'IIIa, 96 % for ermB, 90 % for tetM and 80 % for catA in
      isolates resistant to Kan, Ery, Tet or Cm, respectively. MLST analysis of 30
      multidrug resistant E. faecalis revealed that ST19, CC21, CC25 and CC55 isolates
      were the most common in cheeses. In conclusion, as in many other European
      countries, French cheeses do contain enterococci with multiple antibiotics
      resistances. However, low occurrence of high-level gentamicin resistant or
      sulfamethoxazole/trimethoprim-resistant enterococci and absence of vancomycin- or
      ampicillin- resistant enterococci indicate that cheeses cannot be considered as a
      major reservoir for nosocomial multi-drug resistant enterococci.

PMID- 22608224
TI  - The evaluation of a PCR-based method for identification of Salmonella enterica
      serotypes from environmental samples and various food matrices.
AB  - The most commonly used method for serotyping Salmonella spp. is based on the
      Kaufmann-White scheme, and is composed of serological reactions using antibodies
      to LPS agglutinins. The multiplex PCR used in this investigation was established
      by Kim et al. to serotype the 30 most common clinical Salmonella serotypes, as
      determined by CDC. The PCR assay consists of two five-plex reactions and a single
      two-plex PCR reaction, based on six genetic loci from Salmonella enterica
      serotype Typhimurium and four loci from S. enterica serotype Typhi. In this
      investigation, we further evaluated the method for serotyping Salmonella spp.
      using a reference collection, environmental samples collected from a Mid-Atlantic
      region tomato farm study, four food matrices spiked with different Salmonella
      serotypes and a proficiency test. The PCR assay was first evaluated using DNA
      isolated from pure cultures of isolates obtained from various clinical and
      environmental samples, and then DNA isolated from broth cultures of food matrices
      of "Red round" and Roma tomatoes, Romaine lettuce, green onions and Serrano
      peppers spiked with serotypes Newport, Typhimurium, Javiana and Saintpaul,
      respectively. The results showed that the PCR assay correctly serotyped
      Salmonella spp. from the clinical, environmental, spiked food matrices, and
      proficiency test samples. These findings are significant because the PCR assay
      was successful in the identification of Salmonella in the spiked samples in a
      broth culture containing other non-salmonella organism. This method may be a
      useful resource for the food safety community.

PMID- 22608225
TI  - Inactivation of feline calicivirus and murine norovirus during Dongchimi
      fermentation.
AB  - Among the traditional fermented vegetables in Korea, Dongchimi is a type of
      kimchi with a large water base. We aimed to investigate the survival of norovirus
      surrogates during Dongchimi fermentation. Dongchimi spiked with feline
      calicivirus (FCV) or murine norovirus (MNV) was prepared following a traditional
      recipe. Dongchimi was initially fermented at room temperature overnight and then
      kept at 4  degrees C. The number of lactic acid bacteria, pH, acidity, and virus
      titer were measured 0, 1, 2, 3, 5, 7, 10, 15, 20 days after fermentation. During
      the fermentation process, lactic acid bacteria and acidity increased. At the end
      of the fermentation, population of FCV and MNV decreased about 4.12 and 1.47 log
      units, respectively. Based on the significant reduction of norovirus surrogate
      during Dongchimi fermentation, we conclude that the risk of norovirus in
      Dongchimi may be low.

PMID- 22608226
TI  - Assessment of the microbial diversity of Brazilian kefir grains by PCR-DGGE and
      pyrosequencing analysis.
AB  - The microbial diversity and community structure of three different kefir grains
      from different parts of Brazil were examined via the combination of two culture
      independent methods: PCR-denaturing gradient gel electrophoresis (PCR-DGGE) and
      pyrosequencing. PCR-DGGE showed Lactobacillus kefiranofaciens and Lactobacillus
      kefiri to be the major bacterial populations in all three grains. The yeast
      community was dominated by Saccharomyces cerevisiae. Pyrosequencing produced a
      total of 14,314 partial 16S rDNA sequence reads from the three grains. Sequence
      analysis grouped the reads into three phyla, of which Firmicutes was dominant.
      Members of the genus Lactobacillus were the most abundant operational taxonomic
      units (OTUs) in all samples, accounting for up to 96% of the sequences. OTUs
      belonging to other lactic and acetic acid bacteria genera, such as Lactococcus,
      Leuconostoc, Streptococcus and Acetobacter, were also identified at low levels.
      Two of the grains showed identical DGGE profiles and a similar number of OTUs,
      while the third sample showed the highest diversity by both techniques.
      Pyrosequencing allowed the identification of bacteria that were present in small
      numbers and rarely associated with the microbial community of this complex
      ecosystem.

PMID- 22608227
TI  - Influence of temperature, pH and NaCl concentration on the maximal growth rate of
      Brochothrix thermosphacta and a bioprotective bacteria Lactococcus piscium CNCM I
      4031.
AB  - The maximum specific growth rate (MU(max)) of Brochothrix thermosphacta, a
      spoilage bacteria of cooked peeled shrimp, and Lactococcus piscium CNCM I-4031, a
      bioprotective strain, was investigated under different conditions of temperature,
      NaCl concentrations and pH. The basic modelling approach used was the Gamma
      concept (gamma-concept) and the model developed was then adapted to shrimp.
      Cardinal growth parameters were quite similar for the two strains, except for
      NaCl. No NaCl was required for growth and the NaCl(max) was three-times higher
      for B. thermosphacta than for L. piscium (62 and 23 g l(-1) respectively).
      However, tolerance to NaCl was higher in seafood than in liquid broth, possibly
      due to presence of osmoltically active molecules. L. piscium and B. thermosphacta
      were psychrotolerant, with T(min) = -4.8 and -3.4  degrees C, T(opt) = 23.4 and
      27.0  degrees C and T(max) = 27.2 and 30.8  degrees C respectively. The optimal
      pH was neutral and growth possible till pH = 4.8 for the two strains, assuming
      possible applications of the bioprotective strain in lightly marinated seafood.
      The MU(max) of B. thermosphacta in shrimp was a little higher than in L. piscium
      whatever the environmental conditions. Validation of the model showed that the
      gamma-concept was suitable for predicting MU(max) of B. thermosphacta in shrimp.
      Data generated in this study can be used to adapt the model to other foods with
      few additional experiments and the effect of different parameters may be added in
      the future. The model was less accurate for the bioprotective strain and the
      effect of NaCl must be studied in more detail directly in the matrix.

PMID- 22608228
TI  - Phylogenetic analyses and toxigenic profiles of Fusarium equiseti and Fusarium
      acuminatum isolated from cereals from Southern Europe.
AB  - Fusarium equiseti and Fusarium acuminatum are toxigenic species that contaminate
      cereal crops from diverse climatic regions. They are common in Spanish cereals.
      The information available on their phylogenetics and toxigenic profiles is,
      however, insufficient to assist risk evaluation. In this work, phylogenetic
      analyses were performed using partial sequences of the translation elongation
      factor gene (EF-1alpha) of F. equiseti and F. acuminatum strains isolated from
      barley and wheat from Spain and other countries. The Northern and Southern
      European F. equiseti strains largely separated into two phylogenetically distinct
      clusters. This suggests the existence of two distinct populations within this
      species, explaining its presence in these regions of markedly different climate.
      Production of type A and B trichothecenes by the Spanish strains, examined in
      wheat cultures using a multitoxin analytical method, indicated that F. equiseti
      could produce deoxynivalenol and nivalenol and other trichothecenes, at
      concentrations that might represent a significant risk of toxin contamination for
      Southern European cereals. F. acuminatum showed low intraspecific genetic
      variability and 58% of the strains could produce deoxynivalenol at low level.
      Neither species was found to produce T-2 or HT-2 toxins. The present results
      provide important phylogenetic and toxigenic information essential for the
      accurate prediction of toxigenic risk.

PMID- 22608229
TI  - RNA fingerprinting analysis of Oenococcus oeni strains under wine conditions.
AB  - Oenococcus oeni is a lactic acid bacterium of economic interest used in
      winemaking. This bacterium is the preferred species for malolactic fermentation
      (MLF) due its adaptability to the chemically harsh wine environment. MLF enhances
      the organoleptic properties and ensures deacidification of wines. The aim of this
      work was the transcriptional characterization of six O. oeni strains, four of
      them selected from distinct winemaking regions of Portugal, as candidates to
      malolactic starters, and two commercial malolactic starters. Using crossed assays
      with wines from different Portuguese winemaking regions, strain characteristic
      transcriptional patterns induced by each wine were analyzed based on Random
      Arbitrarily Primed PCR (RAP-PCR). The obtained results suggest that the starter
      strains showed more constrained and limited transcription profiles, whereas a
      high variation on the distribution of the transcription profiles was observed for
      the regional strains in each wine. According with our results, RAP-PCR is a
      useful technique for a preliminary investigation of strain behavior under
      different wine environmental conditions, which can be applied in field studies to
      monitor differential patterns of global gene expression and to select markers for
      the surveillance of malolactic starters performance in winemaking, as well as for
      quality and safety control.

PMID- 22608230
TI  - Comparison of two extraction methods for the detection of hepatitis A virus in
      semi-dried tomatoes and murine norovirus as a process control by duplex RT-qPCR.
AB  - Enteric viruses are important agents of foodborne diseases. Due to their low
      infectious doses and low concentrations in food samples, an efficient and rapid
      virus concentration method is required for routine control. Because of the
      absence of a reliable cell culture method for most of the enteric viruses
      involved in outbreaks, reverse transcription quantitative real-time PCR (RT-qPCR)
      is now widely used for the detection of RNA viruses in food samples. One of the
      general requirements for viral diagnosis concerns the use of a process control to
      monitor the efficiency of viral particle concentration, nucleic acid extraction
      and the presence of potential inhibitors of the RT-PCR reaction. Recent
      epidemiological studies have linked hepatitis A outbreaks to the consumption of
      semi-dried tomatoes (SDT) in Australia, the Netherlands and France. In this
      study, the virus concentration reference method proposed by the
      CEN/TC275/WG6/TAG4 working group for samples of soft fruit and salad vegetables
      was compared to a method including an ultracentrifugation step to recover
      hepatitis A virus (HAV) in SDT. Murine norovirus (MNV-1) was used as a process
      control and detected simultaneously with HAV in a one-step duplex RT-qPCR in both
      procedures. The LOD of HAV was 10 PFU and 1 PFU of HAV/25 g of SDT in the
      presence or absence of MNV-1 respectively, whatever the method used. We conclude
      that both methods achieved an identical limit of detection and that the MNV-1
      offers a very reliable and simple way to monitor the quality of the extraction
      procedures and the presence of RT-qPCR inhibitors.

PMID- 22608231
TI  - Molecular characterization of lactic acid bacteria and in situ amylase expression
      during traditional fermentation of cereal foods.
AB  - Lactic acid bacteria play an important role in traditional fermented foods
      consumed in different countries. Study of their taxonomic structure and diversity
      is necessary for starter culture selection, improved safety and nutritional
      enhancement. To achieve these objectives, microbial genomic typing methods were
      used to study genetic differences of autochthonous bacteria and their
      distribution in two traditional African fermented cereal foods. A total of 85
      predominant bacterial species were isolated from ogi and kunu-zaki obtained from
      Northern and Southern geographical region of Nigeria. They were identified using
      combination of 16S rRNA gene sequencing, multilocus sequence analysis (MLSA)
      based on rpoA, pheS and atpA genes as well as M13-PCR gel fingerprints. The
      results showed that Lactobacillus fermentum was the most frequently isolated
      species in ogi (71.4%) and kunu-zaki (84.5%). Other species of lactic acid
      bacteria (LAB) identified were Lactobacillus plantarum, Streptococcus
      gallolyticus subsp. macedonicus and Pediococcus pentosaceus. Non lactic acid
      bacteria isolated from these foods were species belonging to the Bacillus and
      Staphylococcus. Non-metric multidimensional scaling (nMDS) analysis of the M13
      PCR fingerprints for LAB strains showed clonal diversity among strains of the
      same species. In vitro and in situ expression of amylase gene during fermentation
      by amylolytic L. plantarum ULAG11 was detected, indicating the potential
      usefulness of such species for development of starter cultures and for controlled
      fermentation processes.

PMID- 22608232
TI  - Prevalence, characterization and sources of Listeria monocytogenes in blue crab
      (Callinectus sapidus) meat and blue crab processing plants.
AB  - Seven blue crab processing plants were sampled to determine the prevalence and
      sources of Listeria spp. and Listeria monocytogenes for two years (2006-2007). A
      total of 488 raw crabs, 624 cooked crab meat (crab meat) and 624 environmental
      samples were tested by standard methods. Presumptive Listeria spp. were isolated
      from 19.5% of raw crabs, 10.8% of crab meat, and 69.5% of environmental samples.
      L. monocytogenes was isolated from 4.5% of raw crabs, 0.2% of crab meat, and 2.1%
      of environmental samples. Ninety-seven percent of the isolates were resistant to
      at least one of the ten antibiotics tested. Eight different serotypes were found
      among 76 L. monocytogenes isolates tested with the most common being 4b, 1/2b and
      1/2a. Automated EcoRI ribotyping differentiated 11 ribotypes among the 106 L.
      monocytogenes isolates. Based on ribotyping analysis, the distribution of the
      ribotypes in each processing plant had a unique contamination pattern. A total of
      92 ApaI and 88 AscI pulsotypes among the 106 L. monocytogenes isolates were found
      and distinct pulsotypes were observed in raw crab, crab meat and environmental
      samples. Ribotypes and serotypes recovered from crab processing plants included
      subtypes that have been associated with listeriosis cases in other food
      outbreaks. Our findings suggest that molecular methods may provide critical
      information about sources of L. monocytogenes in crab processing plants and will
      augment efforts to improve food safety control strategies such as targeting
      specific sources of contamination and use of aggressive detergents prior to
      sanitizing.

PMID- 22608233
TI  - Polyphasic approach for quantitative analysis of obligately heterofermentative
      Lactobacillus species in cheese.
AB  - Obligately heterofermentative lactobacilli (OHL) present in cheese during
      ripening can influence the flavour and texture of the final product. In order to
      better evaluate, follow and control this population, there is a current need for
      easy-to-use tools. In this study, a culture-dependent quantitative method (ABEV
      medium) was set up for direct and selective enumeration of total OHL from cheese,
      and a culture-independent method based on specific real time PCR (qPCR) assays
      was developed to target Lactobacillus fermentum and Lactobacillus parabuchneri
      individual species. These tools were applied for OHL quantification in
      manufactured Emmental and Tomme cheeses. The ABEV medium was well adapted for
      specific enumeration and isolation of OHL species present in milk-derived
      samples, even in the presence of background microbiota. qPCR assays showed 100%
      specificity and could accurately quantify the targeted species in various types
      of cheese. Culture-dependent and -independent techniques evaluated in
      manufactured cheese samples generated similar bacterial counts. The behaviour of
      L. fermentum and L. parabuchneri was characterized from milk samples to the end
      of ripening. In addition, PCR-TTGE was used to confirm the presence of inoculated
      species and to globally analyze the composition of naturally present species.
      This polyphasic approach illustrates the complementarity of the different
      methods.

PMID- 22608234
TI  - Levansucrase and sucrose phoshorylase contribute to raffinose, stachyose, and
      verbascose metabolism by lactobacilli.
AB  - Raffinose family oligosaccharides (RFOs) in food are considered anti-nutritional
      factors. This study elucidated the role of alpha-galactosidase (alpha-Gal),
      levansucrase, and sucrose phosphorylase for conversion of RFOs by lactobacilli.
      Quantification of gene expression by reverse-transcriptase quantitative PCR
      revealed that expression of levansucrase and sucrose phosphorylase by
      Lactobacillus reuteri is increased more than 100 fold when sucrose or raffinose
      are available. Fava bean (Vicia faba) or field pea (Pisum sativum) flours were
      fermented with alpha-Gal positive L. reuteri or alpha-Gal negative Lactobacillus
      sanfranciscensis. Isogenic strains lacking levansucrase activity, a L. reuteri
      ftfA mutant and a L. sanfranciscensis levS mutant, were used for comparison.
      During growth in pulse flours, L. sanfranciscensis accumulated melibiose and
      alpha-galactooligosaccharides (alpha-GOSs); the levansucrase-negative strain did
      not grow. L. reuteri metabolized raffinose, stachyose, and verbascose by
      levansucrase activity and accumulated alpha-GOSs as metabolic intermediates.
      Oligosaccharide metabolism in the levansucrase-negative mutant was slower, and
      accumulation of alpha-GOSs was not observed. The use of sorghum sourdough
      fermented with L. reuteri LTH5448 and bean flour in gluten-free baking converted
      RFOs to alpha-GOSs by levansucrase and invertase activities. In conclusion, the
      elucidation of the role levansucrase in RFO metabolism by lactobacilli allowed
      the conversion or hydrolysis of RFOs in food fermentations.

PMID- 22608235
TI  - Glutathione improves the cold resistance of Lactobacillus sanfranciscensis by
      physiological regulation.
AB  - The microenvironmental manipulation of glutathione (GSH) on improving cold
      resistance of Lactobacillus sanfranciscensis DSM 20451(T) was investigated in
      this study. It was proved that GSH relieves the metabolic disorder of cells under
      cold stress, and prevents the decreased activities of related key enzymes such as
      pyruvate kinase (PK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and
      lactate dehydrogenase (LDH) upon cold challenges. Higher intracellular ATP level
      was also found in cells with GSH under cold stress. Moreover, cells with imported
      GSH had significantly higher intracellular than the control during cold
      treatment. In addition, proteomics analysis showed more exciting findings that
      the protective function of GSH under cold stress was related to metabolic
      regulation and the multi-control against induced cross-stresses. These results
      broaden the knowledge about the physiological function of GSH, and suggest a
      practicable approach to improve the cold resistance of L. sanfranciscensis, a
      starter culture for sourdough, by the addition of GSH.

PMID- 22608236
TI  - Complex microbiota of a Chinese "Fen" liquor fermentation starter (Fen-Daqu),
      revealed by culture-dependent and culture-independent methods.
AB  - Daqu is a traditional fermentation starter that is used for Chinese liquor
      production. Although partly mechanized, its manufacturing process has remained
      traditional. We investigated the microbial diversity of Fen-Daqu, a starter for
      light-flavour liquor, using combined culture-dependent and culture-independent
      approaches (PCR-DGGE). A total of 190 microbial strains, comprising 109 bacteria
      and 81 yeasts and moulds, were isolated and identified on the basis of the
      sequences of their 16S rDNA (bacteria) and 26S rDNA and ITS regions (fungi). DGGE
      of DNA extracted from Daqu was used to complement the culture-dependent method in
      order to include non-culturable microbes. Both approaches revealed that Bacillus
      licheniformis was an abundant bacterial species, and Saccharomycopsis fibuligera,
      Wickerhamomyces anomalus, and Pichia kudriavzevii were the most common yeasts
      encountered in Fen-Daqu. Six genera of moulds (Absidia, Aspergillus, Mucor,
      Rhizopus, Rhizomucor and Penicillium) were found. The potential function of these
      microorganisms in starters for alcoholic fermentation is discussed. In general
      the culture-based findings overlapped with those obtained by DGGE by a large
      extent. However, Weissella cibaria, Weissella confusa, Staphylococcus
      saprophyticus, Enterobacter aerogenes, Lactobacillus sanfranciscensis,
      Lactobacillus lactis, and Bacillus megaterium were only revealed by DGGE.

PMID- 22608237
TI  - Detection and identification of wild yeast in Koumiss.
AB  - Koumiss is a slightly alcoholic fermented mare's milk beverage, originally
      obtained by using a natural mixed starter of lactic acid bacteria and yeasts.
      Yeast is an important component of Koumiss processing which can affect the aroma,
      texture, as well as the nutrients beneficial to human health, but few reports
      have examined the yeast ecology of local ecosystems. The purpose of this study
      was to isolate and identify the yeast present in Koumiss from three
      representative regions of China using a polyphasic method. A total of 655 yeast
      isolates were obtained from 96 Koumiss samples collected from three regions in
      China. Koumiss harbored yeast populations at 5-7 log CFU/ml. Twelve different
      yeast species belonging to nine genera were detected in the Koumiss samples
      tested, including Candida pararugosa, Dekkera anomala, Geotrichum sp.,
      Issatchenkia orientalis, Kazachstania unispora, Kluyveromyces marxianus, Pichia
      deserticola, Pichia fermentans, Pichia manshurica, Pichia membranaefaciens,
      Saccharomyces cerevisiae and Torulaspora delbrueckii. Kluyveromyces marxianus,
      Kazachstania unispora and Saccharomyces cerevisiae were the dominant species
      present in this traditional fermented dairy product. This study is the first to
      identify the yeast communities associated with Koumiss in China. The results
      enrich our knowledge of yeast in Koumiss, give us a more complete picture of the
      microbial diversity in Koumiss and can be used to promote the development of the
      local dairy industry.

PMID- 22608238
TI  - Occurrence of toxigenic Clostridium difficile in edible bivalve molluscs.
AB  - Clostridium difficile is an anaerobic bacterium commonly considered to be
      responsible for antibiotic-associated gastrointestinal diseases, ranging from
      diarrhea of varying severity to pseudomembranous colitis. The aim of this study
      was to assess the occurrence of C. difficile in marine edible bivalve molluscs,
      which, as filter feeding organisms, are able to accumulate particles suspended in
      water, including microorganisms. Samples of Mytilus galloprovincialis, Tapes
      philippinarum, and Venus verrucosa were collected from mussel farms and
      fishmongers in the province of Naples (Southern Italy). C. difficile was found in
      49% of the 53 samples investigated. Sixteen isolates were grouped in 12 known
      different PCR ribotypes (001, 002, 003, 010, 012, 014/020, 018, 045, 070, 078,
      106, and 126), whereas 10 additional isolates were grouped in 8 new PCR
      riboprofiles. Two toxinotypes (0 and V) were found. Fifty eight percent of the
      isolates were toxigenic. These findings indicate that toxigenic C. difficile
      strains can be isolated in bivalve molluscs. Marine filter feeding organisms,
      therefore, may be considered as reservoir of toxigenic strains of C. difficile.
      The ingestion of raw or poorly cooked contaminated seafood and the high
      temperature resistance of the spore-forming C. difficile could represent an
      important source of exposure and pose human health concern.

PMID- 22608239
TI  - Caregiving for elders in first nations communities: social system perspective on
      barriers and challenges.
AB  - This research examined the perspectives and experiences of First Nations
      community members regarding health and social support for elderly people living
      in 13 First Nations communities in northwestern Ontario. Surveys (n = 216) and
      focus groups (n = 70) were conducted in 2005 and 2006 with elderly Aboriginal
      people and their formal and informal caregivers. Results indicated a strong
      preference (69%) for helping people to age and die at home; however, barriers and
      challenges existed at the family, community, health system, and social policy
      levels. Barriers included a lack of family caregivers and shortage of health care
      providers and programs; changing community values; and limited access to
      provincial health services and culturally relevant and safe care, all of which
      hindered social policy and community empowerment. Enabling elderly people to age
      within First Nations communities will require multi-level and multi-sectoral
      system changes.

PMID- 22608240
TI  - Divergent brain network connectivity in amyotrophic lateral sclerosis.
AB  - Using resting state (RS) functional magnetic resonance imaging and independent
      component analysis, the integrity of brain networks related to cognition and
      behavior was investigated in 20 nondemented patients with amyotrophic lateral
      sclerosis (ALS). The association between RS functional connectivity and executive
      functions was assessed in 16 patients with neuropsychological assessment. ALS
      patients compared with control subjects showed a decreased connectivity of the
      right orbitofrontal cortex, and an enhanced connectivity of the left precuneus in
      the default mode network; a decreased connectivity of the left inferior frontal
      cortex, and an increased connectivity of the right angular gyrus in the right
      frontoparietal network; and an increased connectivity of the parietal cortex in
      the left frontoparietal network. The enhanced parietal connectivity was
      associated with the clinical and cognitive deficits of the patients. In ALS, an
      alteration of large-scale functional brain networks associated with cognition
      does occur, even in the absence of overt dementia. The increased parietal
      connectivity may have a role in an attempt to maintain cognitive efficiency in
      the presence of structural frontotemporal injury.

PMID- 22608242
TI  - Conducting an efficient proactive risk assessment prior to CPOE implementation in
      an intensive care unit.
AB  - PURPOSE: To develop, conduct, and evaluate a proactive risk assessment (PRA) of
      the design and implementation of CPOE in an ICU. METHODS: We developed a PRA
      method based on issues identified from documented experience with conventional
      PRA methods and the constraints of an organization about to implement CPOE in an
      intensive care unit. The PRA method consists of three phases: planning (three
      months), team (one five-hour meeting), and evaluation (short- and long-term).
      RESULTS: Sixteen unique relevant vulnerabilities were identified as a result of
      the PRA team's efforts. Negative consequences resulting from the vulnerabilities
      included potential patient safety and quality of care issues, non-compliance with
      regulatory requirements, increases in cognitive burden on CPOE users, and/or
      worker inconvenience or distress. Actions taken to address the vulnerabilities
      included redesign of the technology, process (workflow) redesign, user training,
      and/or ongoing monitoring. Verbal and written evaluation by the team members
      indicated that the PRA method was useful and that participants were willing to
      participate in future PRAs. Long-term evaluation was accomplished by monitoring
      an ongoing "issues list" of CPOE problems identified by or reported to IT staff.
      Vulnerabilities identified by the team were either resolved prior to CPOE
      implementation (n=7) or shortly thereafter (n=9). No other issues were identified
      beside those identified by the team. CONCLUSIONS: Generally positive results from
      the various evaluations including a long-term evaluation demonstrate the value of
      developing an efficient PRA method that meets organizational and contextual
      requirements and constraints.

PMID- 22608243
TI  - Evaluation of Schmorl's nodes using F-18 FDG PET/CT.
AB  - AIM: To evaluate the image findings of Schmorl's nodes on combined 2-[(18)F]
      fluoro-2-deoxy-d-glucose positron-emission tomography/computed tomography (FDG
      PET/CT). MATERIALS AND METHODS: Twelve patients who were diagnosed with Schmorl's
      nodes and had undergone magnetic resonance imaging (MRI) and FDG PET/CT were
      retrospectively recruited for this study. The period between the MRI and the FDG
      PET/CT examinations was within 1 week. The demographic data and clinical history
      were reviewed. The relationship between MRI findings and the values of maximum
      standardized uptake value (SUVmax) on FDG PET/CT was analysed. RESULTS: The mean
      values of early and delayed SUVmax of Schmorl's nodes without MRI enhancement
      were 1.14 +/- 0.28 and 1.09 +/- 0.32. The mean values of early and delayed SUVmax
      of Schmorl's nodes with MRI enhancement were 1.73 +/- 0.49 and 1.75 +/- 0.54.
      There were significant differences in the early and delayed SUVmax between
      Schmorl's nodes with and without perifocal enhancement on MRI with Wilcoxon's
      rank-sum test (p = 0.012; p = 0.006). There was a trend of positive correlation,
      although not statistically significant, between delayed SUVmax on FDG PET/CT and
      age in Schmorl's nodes with Spearman's rank correlation (B = 0.86, p = 0.056).
      CONCLUSIONS: Schmorl's nodes demonstrated low to moderate uptake on FDG PET/CT
      images. Schmorl's nodes with perifocal enhancement on MRI result in higher FDG
      uptake. The possibility of false positives caused by Schmorl's nodes should be
      considered when interpreting FDG PET/CT images of bone metastases, especially in
      the aging population.

PMID- 22608241
TI  - Immunization targeting a minor plaque constituent clears beta-amyloid and rescues
      behavioral deficits in an Alzheimer's disease mouse model.
AB  - Although anti-human beta-amyloid (Abeta) immunotherapy clears brain beta-amyloid
      plaques in Alzheimer's disease (AD), targeting additional brain plaque
      constituents to promote clearance has not been attempted. Endogenous murine Abeta
      is a minor Abeta plaque component in amyloid precursor protein (APP) transgenic
      AD models, which we show is ~3%-8% of the total accumulated Abeta in various
      human APP transgenic mice. Murine Abeta codeposits and colocalizes with human
      Abeta in amyloid plaques, and the two Abeta species coimmunoprecipitate together
      from brain extracts. In the human APP transgenic mouse model Tg2576, passive
      immunization for 8 weeks with a murine-Abeta-specific antibody reduced beta
      amyloid plaque pathology, robustly decreasing both murine and human Abeta levels.
      The immunized mice additionally showed improvements in two behavioral assays,
      odor habituation and nesting behavior. We conclude that passive anti-murine Abeta
      immunization clears Abeta plaque pathology--including the major human Abeta
      component--and decreases behavioral deficits, arguing that targeting minor
      endogenous brain plaque constituents can be beneficial, broadening the range of
      plaque-associated targets for AD therapeutics.

PMID- 22608244
TI  - Changes in spleen volume after resection of hepatic colorectal metastases.
AB  - AIM: To identify and describe changes in spleen volume occurring in patients with
      colorectal metastases to the liver after partial hepatectomy. MATERIALS AND
      METHODS: Forty-one consecutive patients (20 men, 21 women) with histopathology
      proven colorectal liver metastases who underwent partial hepatectomy between
      August 2007 and April 2011 were included. Liver and spleen volumes were measured
      by computed tomography (CT) volumetry on the most recent CT prior to surgery and
      on all CTs obtained within a year after partial hepatectomy. Patients were
      carefully evaluated for and excluded if they had co-morbid conditions known to
      cause splenomegaly or risk factors for portal hypertension such as underlying
      liver disease and portal vein thrombosis. RESULTS: Thirty-two (78%) patients
      demonstrated an increase in spleen volume on the first post-operative CT, with
      more than a double increase in volume amongst five patients. Spleen volume
      increased by an average of 43% within 3 months of partial hepatectomy (p <
      0.0001) and remained increased through 6 months after surgery, returning to near
      baseline thereafter. In the remaining nine (22%) patients, the spleen was
      observed to decrease an average of 11% in volume on first postoperative CT (p <
      0.005). CONCLUSIONS: Splenic enlargement after partial hepatectomy of colorectal
      metastases is a common finding on CT. Increased familiarity amongst radiologists
      of this phenomenon as likely reflecting physiological changes is important in
      order to avoid unnecessary evaluation for underlying conditions causing interval
      enlargement of the spleen.

PMID- 22608245
TI  - Radiology of vocal cord palsy.
AB  - Imaging is frequently carried out for the investigation of vocal cord palsy, and
      cord palsy needs to be considered as a sign of a more sinister underlying
      disease. The reporting radiologist needs to be aware of the relevant anatomy of
      the vagus and recurrent laryngeal nerves so that the responsible disease process
      can be identified. It is also important to recognize situations where a lesion at
      the level of the brainstem or skull base may be responsible, as a different
      imaging strategy often needs to be adopted in these cases. This review will also
      consider the laryngeal signs of cord palsy, as although cord palsy is often
      diagnosed clinically, up to 30% of cases may be asymptomatic and clinically
      unsuspected.

PMID- 22608246
TI  - 3D-FIESTA MRI at 3 T demonstrating branches of the intraparotid facial nerve,
      parotid ducts and relation with benign parotid tumours.
AB  - AIM: To investigate the usefulness of three-dimensional (3D) fast imaging
      employing steady state precession (FIESTA) magnetic resonance imaging (MRI) at 3
      T in evaluating the intraparotid components of the facial nerve and parotid
      ducts, and to compare the MRI images with surgical findings. MATERIALS AND
      METHODS: Thirty-one cases of benign parotid tumours were studied with
      conventional and 3D FIESTA MRI sequences at 3T using a head coil. The most
      clinically useful 3D FIESTA images were acquired at parameters of 4.9 ms
      repetition time (TR); 1.5 effective echo time (TEeff); a flip of 55 degrees , a
      field of view of 18 to 20 cm, a matrix of 512 * 320, an axial plane, no gaps, and
      a section thickness of 1 mm. Post-processed multiplanar images were obtained with
      an Advantage Windows (AW sdc 4.3) workstation. Parotid ducts, facial nerves, and
      tumours were identified on these images. The relationship of the tumours to the
      facial nerves and parotid ducts was confirmed at surgery. RESULTS: The facial
      nerves appeared as linear structures of low intensity. The main trunk of the
      facial nerve was identified bilaterally in 93.5% of the 3D-FIESTA sequence
      images. Parotid ducts appeared as structures of high intensity on multiplanar 3D
      FIESTA images (100%). The relationships of the tumours with the cervicofacial and
      temporofacial divisions of the facial nerve were correctly diagnosed in 26 of 31
      cases (83.9%) using 3D-FIESTA sequence images. CONCLUSION: 3D-FIESTA MRI at 3 T
      depicted the main trunk, cervicofacial and temporofacial divisions of the facial
      nerve, and the main parotid duct. It is useful for preoperative evaluation of
      parotid gland tumours.

PMID- 22608247
TI  - Receiver operating characteristic curve analysis, sensitivity comparison and
      individual difference.

PMID- 22608248
TI  - Cerebral fat embolism syndrome in sickle cell anaemia/beta-thalassemia:
      Importance of susceptibility-weighted MRI.

PMID- 22608249
TI  - Percutaneous endoarterectomy: unusual complication during thoracic endovascular
      repair.

PMID- 22608250
TI  - Histologically benign but clinically malignant neoplasms in the thorax: CT
      pathological overview.
AB  - The purpose of this article is to review the computed tomography (CT) and
      histopathological features of uncommon primary neoplasms of the thorax that can
      manifest clinically malignant features (multiplicity of pulmonary nodules, an
      invasive nature, and metastases or recurrence after surgery) with little evidence
      of histological malignancy.

PMID- 22608251
TI  - Oxidised LDL/LDL-cholesterol ratio and coronary artery calcification in
      haemodialysis patients.
AB  - BACKGROUND AND AIMS: Serum malondialdehyde-modified low-density lipoprotein (MDA
      LDL) and MDA-LDL/LDL-cholesterol (LDL-c) ratio are risk factors for
      arteriosclerosis and cardiovascular disease (CVD). However, no information is
      available on these parameters or their associations with coronary artery
      calcification (CAC) in haemodialysis (HD) patients. METHODS AND RESULTS: Fifty
      seven HD patients and 26 control subjects were included in this cross-sectional
      study. Serum MDA-LDL concentrations and MDA-LDL/LDL-c ratios were examined. HD
      patients had significantly higher MDA-LDL/LDL-c ratios than the controls (105.1
      +/- 27.5 vs. 81.4 +/- 18.9 mU/mg, P < 0.001); however, there was no significant
      difference in serum MDA-LDL levels between the 2 groups. CAC scores were examined
      only in HD patients and their possible associations with the clinical/laboratory
      data were analysed. Analysis of HD patients showed that MDA-LDL/LDL-c ratio has
      an association with presence of CVD, CAC score, HD duration, MDA-LDL, or
      haemoglobin A1C. In addition, the CAC score was positively correlated with serum
      MDA-LDL level (P = 0.048) and MDA-LDL/LDL-c ratio (P = 0.006). Furthermore,
      multivariate logistic regression analysis showed that MDA-LDL/LDL-c ratio (beta =
      0.04, P = 0.003) and HD duration (beta = 0.16, P = 0.007) were independently
      associated with CAC score. CONCLUSION: The MDA-LDL/LDL-c ratio of HD patients was
      significantly higher than that of non-HD subjects and was independently
      associated with the CAC score. Therefore, this ratio could be an important risk
      factor for CAC in HD patients.

PMID- 22608253
TI  - Preclinical and clinical studies of estrogen deprivation support the PDGF/Abl
      pathway as a novel therapeutic target for overcoming endocrine resistance in
      breast cancer.
AB  - INTRODUCTION: The majority of breast tumors at primary diagnosis are estrogen
      receptor positive (ER+). Estrogen (E) mediates its effects by binding to the ER.
      Therapies targeting the estrogenic stimulation of tumor growth reduce mortality
      from ER+ breast cancer. However, resistance remains a major clinical problem.
      METHODS: To identify molecular mechanisms associated with resistance to E
      deprivation, we assessed the temporal changes in global gene expression during
      adaptation to long-term culture of MCF7 human breast cancer cells in the absence
      of estradiol (E2), long term estrogen deprived (LTED), that leads to recovery of
      proliferative status and models resistance to an aromatase inhibitor (AI). The
      expression levels of proteins were determined by western blotting. Proliferation
      assays were carried out using the dual platelet derived growth factor receptor
      (PDGFR)/Abelson tyrosine kinase (Abl) inhibitor nilotinib. Luciferase reporter
      assays were used to determine effects on ER-mediated transactivation. Changes in
      recruitment of cofactors to the gene regulated by estrogen in breast cancer 1
      (GREB1) promoter were determined by chromatin immunoprecipitation (ChIP). Gene
      expression data were derived from 81 postmenopausal women with ER+ BC pre
      treatment and at two-weeks post-treatment with single agent anastrozole in a
      neoadjuvant trial. RESULTS: The PDGF/Abl canonical pathway was significantly
      elevated as early as one week post E-deprivation (P = 1.94 E-04) and this became
      the top adaptive pathway at the point of proliferative recovery (P = 1.15 E-07).
      Both PDGFRbeta and Abl protein levels were elevated in the LTED cells compared to
      wild type (wt)-MCF7 cells. The PDGF/Abl tyrosine kinase inhibitor nilotinib,
      suppressed proliferation in LTED cells in the presence or absence of E. Nilotinib
      also suppressed ER-mediated transcription by destabilizing the ER and reducing
      recruitment of amplified in breast cancer-1 (AIB1) and the CREB binding protein
      (CBP) to the promoter of the E-responsive gene GREB1. High PDGFRbeta in primary
      ER+ breast cancer of 81 patients prior to neoadjuvant treatment with an AI was
      associated with poorer antiproliferative response. Additionally PDGFRbeta
      expression increased after two weeks of AI therapy (1.25 fold, P = 0.003).
      CONCLUSIONS: These preclinical and clinical data indicate that the PDGF/Abl
      signaling pathway merits clinical evaluation as a therapeutic target with
      endocrine therapy in ER+ breast cancer.

PMID- 22608254
TI  - The immunobiology of IL-27.
AB  - Like many cytokines, IL-27 has pleiotropic properties that can limit or enhance
      ongoing immune responses depending on context. Thus, under certain circumstances,
      IL-27 can promote TH1 differentiation and has been linked to the activation of
      CD8(+) T cells and enhanced humoral responses. However, IL-27 also has potent
      inhibitory properties and mice that lack IL-27 mediated signaling develop
      exaggerated inflammatory responses in the context of infection or autoimmunity.
      This chapter reviews in depth the biology of IL-27, including the initial
      discovery, characterization, and signaling mediated by IL-27 as well as more
      recent insights into the molecular and cellular basis for its pleiotropic
      effects. Many of these advances are relevant to human diseases and highlight the
      potential of therapies that harness the regulatory properties of IL-27.

PMID- 22608255
TI  - Autoimmune arthritis: the interface between the immune system and joints.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease, characterized by chronic
      inflammation and synovial hyperplasia in the joints that ultimately lead to
      cartilage and bone destruction. A wealth of research has shown that CD4(+) T
      cells, especially IL-17 producing helper T (Th17) cells, play an important role
      in RA development. However, it still remains to be clarified how the systemic
      immune response results in the local joint disorders. Studies on animal models of
      RA have shed light on the importance of the interaction between immune cells and
      joint-specific mesenchymal cells. In particular, joint-specific mesenchymal cells
      contribute to the Th17-mediated augmentation of the inflammatory phase in RA by
      promoting the migration of Th17 cells to the inflammatory joint and then
      homeostatic proliferation with increase in IL-17 production. In addition, recent
      progress in osteoimmunology has provided new insights into the pathogenesis of
      the bone destruction phase in RA. Of note, Th17 cells have been shown to enhance
      the differentiation of osteoclasts via joint-specific mesenchymal cells. Thus,
      the interaction of CD4(+) T cells and nonhematopoietic mesenchymal cells in
      joints plays a key role in RA pathogenesis during both the inflammatory and bone
      destruction phases. Focusing on this interaction will lead to a better
      understanding of the mechanism by which the systemic immune response results in
      local joint disorders and also helps provide a molecular basis for novel
      therapeutic strategies.

PMID- 22608256
TI  - Immunological tolerance during fetal development: from mouse to man.
AB  - The development of the adaptive immune system has been studied in the mouse
      primarily because it is easier to access fetal tissues and because there exists a
      rich array of probes for analysis of various components of the immune system.
      While much has been learned from this exercise, it is also clear that different
      species show substantial temporal variation in the development of the immune
      system during early life. In mice, for instance, mature alpha/beta T cells first
      appear in the periphery during the final stages of fetal gestation and only
      increase in number after birth (Friedberg and Weissman, 1974); in humans, on the
      other hand, the first mature alpha/beta T cells are seen in peripheral tissues at
      10-12 gestational weeks (g.w.) and are circulating in significant numbers by the
      end of the second trimester (Ceppellini et al., 1971; Haynes et al., 1988;
      Hayward and Ezer, 1974; Kay et al., 1970). Although the functional implications
      of these differences remain unclear, it is likely that there are significant
      biological consequences associated with the relatively early development of the
      peripheral adaptive immune system in humans, for example, with respect to the
      development of peripheral tolerance as well as to the response to antigens that
      might cross the placenta from the mother (e.g., cells bearing noninherited
      maternal alloantigens, infectious agents, food antigens, and the like). Here, we
      will review studies of immune system ontogeny in the mouse and in humans, and
      then focus on the possible functional roles of fetal T cell populations during
      development and later in life in humans.

PMID- 22608257
TI  - Mapping lupus susceptibility genes in the NZM2410 mouse model.
AB  - Considerable efforts have been deployed over the years to decipher the genetic
      basis of systemic lupus erythematosus (SLE). The NZM2410 strain is murine model
      in which the genetic analysis of SLE is the most advanced. NZM2410 studies have
      shown that, as in SLE patients, lupus susceptibility is achieved by the
      coexpression of many susceptibility alleles, each of which with a small
      contribution to the overall disease phenotype. This mouse model has also revealed
      the critical role played by gene-gene interactions, which are believed to be an
      essential contribution to human SLE heritability, although it has been much more
      difficult to characterize. We have now reached a phase in which NZM2410
      susceptibility genes have been identified, all them novel in their association
      with lupus or even with immune functions. Ongoing studies geared at understanding
      how these genes impact immune tolerance and interact with each other in the
      mouse, and their impact on the human immune system or target organs, will
      undoubtedly lead to important discovery for a better understanding on the disease
      and potential identification of therapeutic targets.

PMID- 22608259
TI  - An emerging role of RNA-binding proteins as multifunctional regulators of
      lymphocyte development and function.
AB  - Sequence-specific RNA-binding proteins (RBP) and the regulation of RNA decay have
      long been recognized as important regulators of the inflammatory response. RBP
      influence gene expression throughout the lifespan of the mRNA by regulating
      splicing, polyadenylation, cellular localization, translation, and decay.
      Increasing evidence now indicates that these proteins, together with the RNA
      decay machinery that they recruit, also regulate the development and activation
      of lymphocytes. The activity of RBP is regulated by the same signal transduction
      pathways that govern lymphocyte development and differentiation in response to
      antigen and cytokine receptor engagement. Roles for these proteins in regulating
      the diverse functions of lymphocytes are becoming increasingly apparent.

PMID- 22608260
TI  - Active and passive anticytokine immune therapies: current status and development.
AB  - Anticytokine (AC) immune therapies derived from vaccine procedures aim at
      enhancing natural immune defense mechanisms ineffective to contain abnormally
      produced cytokines and counteract their pathogenic effects. Given their short
      half-life, cytokines, the production of which by effector immune cells (T and B
      lymphocytes, antigen-presenting cells (APCs), natural killer (NK) and endothelial
      cells) is inducible and controlled by negative feedback regulation, (1) exert
      locally their signaling to paracrine/autocrine target responder cells carrying
      high-affinity membrane receptors and (2) are commonly present at minimal
      concentration in the body fluid (lymph, serum). Aberrant signaling triggered by
      cytokines, uncontrolly released by effector immune cells or produced by cancer
      and other pathologic cells, contribute to the pathogenesis of chronic diseases
      including cancer, viral infections, allergy, and autoimmunity. To block these
      ectopic cytokine signaling and prevent their pathogenic effects, AC Abs supplied
      either by injections (passive AC immune therapy) or elicited by immunization with
      cytokine-derived immunogenes called Kinoids (active AC immune therapy) proved to
      be experimentally effective and safe. In this review, we detailed the rationale
      and the requirements for the use of AC immunotherapies in humans, the proof of
      efficacy of these medications in animal disease models, and their current
      clinical development and outcome, including adverse side effects they may
      generate. We particularly show that, to date, the benefit:risk ratio of AC immune
      therapies is highly positive.

PMID- 22608258
TI  - Functional heterogeneity in the basophil cell lineage.
AB  - CD4(+) T-helper type 2 (Th2) cells, characterized by their expression of
      interleukin (IL)-4, IL-5, IL-9, and IL-13, are required for immunity to helminth
      parasites and promote the pathological inflammation associated with asthma and
      allergic diseases. Recent reports from a number of laboratories have indicated
      that basophils can influence the induction and/or effector stages of Th2 cytokine
      mediated inflammation. However, the impact of basophils appears to depend on the
      anatomical location and nature of the infectious or inflammatory stimulus. This
      review highlights the factors that regulate basophil development and activation
      and describes known basophil effector functions. Further, we discuss the recent
      identification of phenotypic and functional heterogeneity within murine and human
      basophil populations and discuss how these findings may explain the context
      dependent influence of basophils on either the propagation, regulation, or
      effector phases of Th2 cytokine-associated inflammation.

PMID- 22608261
TI  - Mature results of a phase II trial on individualised accelerated radiotherapy
      based on normal tissue constraints in concurrent chemo-radiation for stage III
      non-small cell lung cancer.
AB  - BACKGROUND: Sequential chemotherapy and individualised accelerated radiotherapy
      (INDAR) has been shown to be effective in non-small cell lung cancer (NSCLC),
      allowing delivering of high biological doses. We therefore performed a phase II
      trial (clinicaltrials.gov; NCT00572325) investigating the same strategy in
      concurrent chemo-radiation in stage III NSCLC. METHODS: 137 stage III patients
      fit for concurrent chemo-radiation (PS 0-2; FEV(1) and DLCO >= 30%) were included
      from April 2006 till December 2009. An individualised prescribed dose based on
      normal tissue dose constraints was applied: mean lung dose (MLD) 19 Gy, spinal
      cord 54 Gy, brachial plexus 66 Gy, central structures 74 Gy. A total dose between
      51 and 69 Gy was delivered in 1.5 Gy BID up to 45 Gy, followed by 2 Gy QD.
      Radiotherapy was started at the 2nd or 3rd course of chemotherapy. Primary end
      point was overall survival (OS) and secondary end-point toxicity common
      terminology criteria for adverse events v3.0 (CTCAEv3.0). FINDINGS: The median
      tumour volume was 76.4 +/- 94.1 cc; 49.6% of patients had N2 and 32.1% N3
      disease. The median dose was 65.0 +/- 6.0 Gy delivered in 35 +/- 5.7 days. Six
      patients (4.4%) did not complete radiotherapy. With a median follow-up of 30.9
      months, the median OS was 25.0 months (2-year OS 52.4%). Severe acute toxicity
      (>= G3, 35.8%) consisted mainly of G3 dysphagia during radiotherapy (25.5%).
      Severe late toxicity (>= G3) was observed in 10 patients (7.3%). INTERPRETATION:
      INDAR in concurrent chemo-radiation based on normal tissue constraints is
      feasible, even in patients with large tumour volumes and multi-level N2-3
      disease, with acceptable severe late toxicity and promising 2-year survival.

PMID- 22608262
TI  - NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: a
      randomised phase III trial of a novel treatment modality.
AB  - PURPOSE: NovoTTF-100A is a portable device delivering low-intensity, intermediate
      frequency electric fields via non-invasive, transducer arrays. Tumour Treatment
      Fields (TTF), a completely new therapeutic modality in cancer treatment,
      physically interfere with cell division. METHODS: Phase III trial of chemotherapy
      free treatment of NovoTTF (20-24h/day) versus active chemotherapy in the
      treatment of patients with recurrent glioblastoma. Primary end-point was
      improvement of overall survival. RESULTS: Patients (median age 54 years (range 23
      80), Karnofsky performance status 80% (range 50-100) were randomised to TTF alone
      (n=120) or active chemotherapy control (n=117). Number of prior treatments was
      two (range 1-6). Median survival was 6.6 versus 6.0 months (hazard ratio 0.86
      [95% CI 0.66-1.12]; p=0.27), 1-year survival rate was 20% and 20%, progression
      free survival rate at 6 months was 21.4% and 15.1% (p=0.13), respectively in TTF
      and active control patients. Responses were more common in the TTF arm (14%
      versus 9.6%, p=0.19). The TTF-related adverse events were mild (14%) to moderate
      (2%) skin rash beneath the transducer arrays. Severe adverse events occurred in
      6% and 16% (p=0.022) of patients treated with TTF and chemotherapy, respectively.
      Quality of life analyses favoured TTF therapy in most domains. CONCLUSIONS: This
      is the first controlled trial evaluating an entirely novel cancer treatment
      modality delivering electric fields rather than chemotherapy. No improvement in
      overall survival was demonstrated, however efficacy and activity with this
      chemotherapy-free treatment device appears comparable to chemotherapy regimens
      that are commonly used for recurrent glioblastoma. Toxicity and quality of life
      clearly favoured TTF.

PMID- 22608263
TI  - ESBL-positive Enterobacteria isolates in drinking water.

PMID- 22608264
TI  - Severe fever with thrombocytopenia syndrome virus, Shandong Province, China.
AB  - Severe fever with thrombocytopenia syndrome, which results in severe illness and
      has a high case-fatality rate, is caused by a novel bunyavirus, severe fever with
      thrombocytopenia syndrome virus. We found that samples from 2/237 (0.8%) healthy
      persons and 111/134 (83%) goats in Yiyuan County, Shandong Province, China, were
      seropositive for this virus.

PMID- 22608265
TI  - Deterring gun crime materially using forensic coatings.
AB  - Surface coatings that can help deter and solve gun crime are described. These
      nanoengineered coatings have been applied and evaluated on brass cartridge cases,
      where they increase associative forensic evidence through nanotag donation to the
      handler and the retention of handler's DNA. In future we expect this approach to
      be used for other surfaces and conditions.

PMID- 22608266
TI  - First systematic evaluation of the potency of Cannabis sativa plants grown in
      Albania.
AB  - Cannabis products (marijuana, hashish, cannabis oil) are the most frequently
      abused illegal substances worldwide. Delta-9-tetrahydrocannabinol (THC) is the
      main psychoactive component of Cannabis sativa plant, whereas cannabidiol (CBD)
      and cannabinol (CBN) are other major but no psychoactive constituents. Many
      studies have already been carried out on these compounds and chemical research
      was encouraged due to the legal implications concerning the misuse of marijuana.
      The aim of this study was to determine THC, CBD and CBN in a significant number
      of cannabis samples of Albanian origin, where cannabis is the most frequently
      used drug of abuse, in order to evaluate and classify them according to their
      cannabinoid composition. A GC-MS method was used, in order to assay cannabinoid
      content of hemp samples harvested at different maturation degree levels during
      the summer months and grown in different areas of Albania. This method can also
      be used for the determination of plant phenotype, the evaluation of psychoactive
      potency and the control of material quality. The highest cannabinoid
      concentrations were found in the flowers of cannabis. The THC concentrations in
      different locations of Albania ranged from 1.07 to 12.13%. The influence of
      environmental conditions on cannabinoid content is discussed. The cannabinoid
      content of cannabis plants were used for their profiling, and it was used for
      their classification, according to their geographical origin. The determined
      concentrations justify the fact that Albania is an area where cannabis is
      extensively cultivated for illegal purposes.

PMID- 22608267
TI  - Individual differences in drivers' cognitive processing of road safety messages.
AB  - Using Gray and McNaughton's (2000) revised reinforcement sensitivity theory (r
      RST), we examined the influence of personality on processing of words presented
      in gain-framed and loss-framed anti-speeding messages and how the processing
      biases associated with personality influenced message acceptance. The r-RST
      predicts that the nervous system regulates personality and that behaviour is
      dependent upon the activation of the behavioural activation system (BAS),
      activated by reward cues and the fight-flight-freeze system (FFFS), activated by
      punishment cues. According to r-RST, individuals differ in the sensitivities of
      their BAS and FFFS (i.e., weak to strong), which in turn leads to stable patterns
      of behaviour in the presence of rewards and punishments, respectively. It was
      hypothesised that individual differences in personality (i.e., strength of the
      BAS and the FFFS) would influence the degree of both message processing (as
      measured by reaction time to previously viewed message words) and message
      acceptance (measured three ways by perceived message effectiveness, behavioural
      intentions, and attitudes). Specifically, it was anticipated that, individuals
      with a stronger BAS would process the words presented in the gain-frame messages
      faster than those with a weaker BAS and individuals with a stronger FFFS would
      process the words presented in the loss-frame messages faster than those with a
      weaker FFFS. Further, it was expected that greater processing (faster reaction
      times) would be associated with greater acceptance for that message. Driver
      licence holding students (N=108) were recruited to view one of four anti-speeding
      messages (i.e., social gain-frame, social loss-frame, physical gain-frame, and
      physical loss-frame). A computerised lexical decision task assessed participants'
      subsequent reaction times to message words, as an indicator of the extent of
      processing of the previously viewed message. Self-report measures assessed
      personality and the three message acceptance measures. As predicted, the degree
      of initial processing of the content of the social gain-framed message mediated
      the relationship between the reward sensitive trait and message effectiveness.
      Initial processing of the physical loss-framed message partially mediated the
      relationship between the punishment sensitive trait and both message
      effectiveness and behavioural intention ratings. These results show that reward
      sensitivity and punishment sensitivity traits influence cognitive processing of
      gain-framed and loss-framed message content, respectively, and subsequently,
      message effectiveness and behavioural intention ratings. Specifically, a range of
      road safety messages (i.e., gain-frame and loss-frame messages) could be designed
      which align with the processing biases associated with personality and which
      would target those individuals who are sensitive to rewards and those who are
      sensitive to punishments.

PMID- 22608268
TI  - Speeding by young novice drivers: What can personal characteristics and
      psychosocial theory add to our understanding?
AB  - PURPOSE: Young novice drivers continue to be overrepresented in fatalities and
      injuries arising from crashes even with the introduction of countermeasures such
      as graduated driver licensing (GDL). Enhancing countermeasures requires a better
      understanding of the variables influencing risky driving. One of the most common
      risky behaviours performed by drivers of all ages is speeding, which is
      particularly risky for young novice drivers who, due to their driving
      inexperience, have difficulty in identifying and responding appropriately to road
      hazards. Psychosocial theory can improve our understanding of contributors to
      speeding, thereby informing countermeasure development and evaluation. This paper
      reports an application of Akers' social learning theory (SLT), augmented by
      Gerrard and Gibbons' prototype/willingness model (PWM), in addition to personal
      characteristics of age, gender, car ownership, and psychological traits/states of
      anxiety, depression, sensation seeking propensity and reward sensitivity, to
      examine the influences on self-reported speeding of young novice drivers with a
      Provisional (intermediate) licence in Queensland, Australia. METHOD: Young
      drivers (n=378) recruited in 2010 for longitudinal research completed two surveys
      containing the Behaviour of Young Novice Drivers Scale, and reported their
      attitudes and behaviours as pre-Licence/Learner (Survey 1) and Provisional
      (Survey 2) drivers and their sociodemographic characteristics. RESULTS: An Akers'
      measurement model was created. Hierarchical multiple regressions revealed that
      (1) personal characteristics (PC) explained 20.3%; (2) the combination of PC and
      SLT explained 41.1%; (3) the combination of PC, SLT and PWM explained 53.7% of
      variance in self-reported speeding. Whilst there appeared to be considerable
      shared variance, the significant predictors in the final model included gender,
      car ownership, reward sensitivity, depression, personal attitudes, and Learner
      speeding. CONCLUSIONS: These results highlight the capacity for psychosocial
      theory to improve our understanding of speeding by young novice drivers,
      revealing relationships between previous behaviour, attitudes, psychosocial
      characteristics and speeding. The findings suggest multi-faceted countermeasures
      should target the risky behaviour of Learners, and Learner supervisors should be
      encouraged to monitor their Learners' driving speed. Novice drivers should be
      discouraged from developing risky attitudes towards speeding.

PMID- 22608269
TI  - Potential biomarkers for disease activity in Takayasu's arteritis.

PMID- 22608270
TI  - JOBSTRESS study: comparison of heart rate variability in emergency physicians
      working a 24-hour shift or a 14-hour night shift--a randomized trial.

PMID- 22608271
TI  - Interventional cardiologists and risk of radiation-induced cataract: results of a
      French multicenter observational study.
AB  - BACKGROUND: Interventional cardiologists (ICs) are exposed to X-rays and may be
      at risk to develop cataract earlier than common senile cataract. Excess risk of
      posterior subcapsular cataract, known as radiation-induced, was previously
      observed in samples of ICs from Malaysia, and Latin America. The O'CLOC study
      (Occupational Cataracts and Lens Opacities in interventional Cardiology) was
      performed to quantify the risk at the scale of France. METHODS: This cross
      sectional multicenter study included an exposed group of ICs from different
      French centers and an unexposed control group of non-medical workers. Individual
      information was collected about cataract risk factors and past and present
      workload in catheterization laboratory. All participants had a clinical eye
      examination to classify the lens opacities (nuclear, cortical, or posterior
      subcapsular) with the international standard classification LOCS III. RESULTS:
      The study included 106 ICs (mean age = 51 +/- 7 years) and 99 unexposed control
      subjects (mean age = 50 +/- 7 years). The groups did not differ significantly in
      the prevalence of either nuclear or cortical lens opacities (61% vs. 69% and 23%
      vs. 29%, respectively). However, posterior subcapsular lens opacities, were
      significantly more frequent among ICs (17% vs. 5%, p=0.006), for an OR=3.9 [1.3
      11.4]. The risk increased with duration of activity but no clear relationship
      with workload was observed. However, the risk appeared lower for regular users of
      protective lead glasses (OR=2.2 [0.4-12.8]). CONCLUSIONS: ICs, in France as
      elsewhere, are at high risk of posterior subcapsular cataracts. Use of protective
      equipment against X-rays, in particular lead glasses, is strongly recommended to
      limit this risk.

PMID- 22608272
TI  - Aortic balloon valvuloplasty in pregnancy for symptomatic severe aortic stenosis.

PMID- 22608273
TI  - Serum pigment epithelium-derived factor levels are independently associated with
      decreased number of circulating endothelial progenitor cells in healthy non
      smokers.

PMID- 22608274
TI  - 200+ years of a misunderstood drug for treating chronic heart failure: digoxin,
      why and how should we continue using it?

PMID- 22608275
TI  - Thromboembolic stroke with concurrent left atrial appendage and left atrial
      septal pouch thrombus.

PMID- 22608277
TI  - The functional landscape of a presynaptic nerve terminal.
AB  - The neuromuscular junction (NMJ) is the original model synapse, and while others
      have emerged, especially as models of plasticity involving coincidence detectors,
      the NMJ continues to provide useful new information. It remains, for example, one
      of the best understood synapses in terms of the relationship between structure
      and function. In particular, the advent of new tools for fluorescence imaging has
      allowed the processes of vesicle exocytosis, endocytosis, and receptor activation
      to be spatially mapped in considerable detail. Here, we will focus on the spatial
      properties of transmitter release at the presynaptic motor terminal at the mouse
      NMJ. The preparation offers several experimental advantages, such as easy
      accessibility, a nearly planar, unobstructed view of several hundred square
      microns of synaptic membrane, as well as a highly stereotyped, consistent
      structure of a fully differentiated adult mammalian synapse.

PMID- 22608278
TI  - The effect of changes in joint angle on the characteristics of physiological
      tremor.
AB  - INTRODUCTION: Physiological tremor, as a whole, can be influenced by changes in
      muscle activity. However, the origin of low-frequency physiological tremor
      oscillations has yet to be conclusively determined. It is possible that by
      experimentally manipulating muscular activity, a better determination of the
      origin of those low-frequency oscillations can be achieved. It was demonstrated
      that changes in joint angle modify characteristics of muscular activity. As such,
      we hypothesize that changes in wrist-joint angle will alter the characteristics
      of low-frequency physiological tremor oscillations. OBJECTIVE: Assess the
      influence of changes in joint angle of the wrist on characteristics of
      physiological finger tremor. METHODS: Physiological finger tremor was recorded (n
      = 25) using a laser displacement system while the arm and hand were supported.
      The relative angle between the dorsum of the hand and the forearm was altered
      between conditions (135 degrees , 180 degrees , 225 degrees  and 270 degrees ),
      while the hand and the finger remained parallel to the ground. EMG of the
      extensors and flexors were also recorded. RESULTS: Tremor amplitude was
      significantly altered by changes in wrist-joint angle. This was especially the
      case for lower frequency oscillations. In addition, electromyography properties
      of forearm muscles were also significantly modified by changes in wrist-joint
      angles. CONCLUSIONS: This study demonstrates that changes in wrist-joint angle
      modify the characteristics of physiological finger tremor. This should be taken
      into account when interpreting tremor data as well as when developing tools to
      minimize tremor.

PMID- 22608279
TI  - Novel formulation of a double threshold algorithm for the estimation of muscle
      activation intervals designed for variable SNR environments.
AB  - The aim of this work is the development of an improved formulation of the double
      threshold algorithm for sEMG onset-offset detection presented by Bonato and co
      workers. The original formulation, which keeps the threshold fixed, suffers from
      performance degradation whenever the SNR changes during the analysis. The novel
      approach is designed to be adaptive to SNR changes in either burst or inter-burst
      zones of sEMG signals recorded in static and dynamic conditions. The detection
      parameters (i.e. detection and false alarm probabilities) are updated on the
      basis of an on-line estimation of the SNR. The proposed formulation has been
      assessed on both simulated and real sEMG data. For constant SNR the performance
      of the original formulation is confirmed (for SNR > 8 dB, bias and standard
      deviation less than 10 and 15 ms, respectively; detection percentage higher than
      95%), while the novel implementation performs better with time-varying SNR (for
      SNR varying in the range 10-25 dB the standard approach detection percentage
      decreases at 50%). Detection on signals recorded during isometric contractions at
      different force levels confirms the performance on simulated signals (StD = 134
      ms; FP = 22%, and StD = 42 ms; FP = 2%, respectively for standard and novel
      implementation calculated as average on five experimental trials). The pseudo
      real-time detection allowed by this formulation can be profitably exploited by
      biofeedback applications based on myoelectric information.

PMID- 22608276
TI  - Mitochondrial Ca(2+) and neurodegeneration.
AB  - Mitochondria are essential for ensuring numerous fundamental physiological
      processes such as cellular energy, redox balance, modulation of Ca(2+) signaling
      and important biosynthetic pathways. They also govern the cell fate by
      participating in the apoptosis pathway. The mitochondrial shape, volume, number
      and distribution within the cells are strictly controlled. The regulation of
      these parameters has an impact on mitochondrial function, especially in the
      central nervous system, where trafficking of mitochondria is critical to their
      strategic intracellular distribution, presumably according to local energy
      demands. Thus, the maintenance of a healthy mitochondrial population is essential
      to avoid the impairment of the processes they regulate: for this purpose, cells
      have developed mechanisms involving a complex system of quality control to remove
      damaged mitochondria, or to renew them. Defects of these processes impair
      mitochondrial function and lead to disordered cell function, i.e., to a disease
      condition. Given the standard role of mitochondria in all cells, it might be
      expected that their dysfunction would give rise to similar defects in all
      tissues. However, damaged mitochondrial function has pleiotropic effects in
      multicellular organisms, resulting in diverse pathological conditions, ranging
      from cardiac and brain ischemia, to skeletal muscle myopathies to
      neurodegenerative diseases. In this review, we will focus on the relationship
      between mitochondrial (and cellular) derangements and Ca(2+) dysregulation in
      neurodegenerative diseases, emphasizing the evidence obtained in genetic models.
      Common patterns, that recognize the derangement of Ca(2+) and energy control as a
      causative factor, have been identified: advances in the understanding of the
      molecular regulation of Ca(2+) homeostasis, and on the ways in which it could
      become perturbed in neurological disorders, may lead to the development of
      therapeutic strategies that modulate neuronal Ca(2+) signaling.

PMID- 22608280
TI  - HDAg-L variants in covert hepatitis D and HBV occult infection among Amerindians
      of Argentina: new insights.
AB  - BACKGROUND: Guidelines suggest that all HBsAg-positive patients should be tested
      for anti-HDV IgG antibodies and to confirm active hepatitis D virus (HDV)
      infection by detection of HDV RNA by reverse transcriptase (RT) polymerase chain
      reaction (PCR). OBJECTIVES: The aim of this study was to determine the
      serological prevalence and molecular features of HDV within an Amerindian
      community from Argentina exhibiting positivity for HBsAg and/or anti-HBc total
      Ig. STUDY DESIGN: Forty-six plasma samples were tested for the detection of total
      anti-HDV antibodies by ELISA. Concomitantly, a partial RNA region coding for the
      delta antigen (HDAg) was amplified by RT-nested PCR (RT-nPCR). In silica
      translation of DNA sequences into the amino acid (aa) sequence of HDAg-S (aa110
      195) and HDAg-L (aa110-214) was performed. RESULTS: Out of 46 HDV non-reactive
      samples by ELISA, 3 were HDV RNA positive by RT-nPCR. These samples were anti-HBc
      only positive, 2 of them identified as cases of occult hepatitis B infection
      (OBI). The 3 cases were HBeAg-negative and showed normal ALT/AST levels. All
      sequences were ascribed to HDV genotype 1, but exhibited nucleotide differences
      in HDAg-L coding region, among which, mutations at codons 197 and 201 -
      reportedly known to promote in vitro an unsuitable interaction with HBsAg - were
      observed. CONCLUSIONS: These results provide evidence of covert HDV infection
      even among OBI, highlighting the need to reevaluate the currently applied
      guidelines for HDV diagnostic algorithms, as well as to explore if the observed
      mutations promote any effect on HDV pathogenesis.

PMID- 22608281
TI  - Stimulation-induced side effects in the posterior subthalamic area: distribution,
      characteristics and visualization.
AB  - OBJECTIVE: The posterior subthalamic area (PSA) is an emerging but relatively
      unexplored target for DBS treatment of tremor. The aim of the study was to
      explore the area further by evaluating the spatial distribution and the
      characteristics of stimulation-induced side effects in this area. METHODS: Twenty
      eight patients with essential tremor (ET) implanted with 33 DBS electrodes were
      evaluated concerning stimulation-induced side effects by testing each contact
      separately one year after surgery. The location of the side effects were plotted
      on axial slides of the Morel Stereotactic Atlas and a 3-dimensional model of the
      area for visualization was created. RESULTS: Visualization of the contacts
      eliciting stimulation-induced side effects demonstrated that identical responses
      can be elicited from various points in the PSA and its vicinity. The majority of
      contacts inducing muscular affection and cerebellar symptoms, including
      dysarthria, could not be attributed to an effect on the internal capsule.
      Paresthesias, affecting various body parts were elicited throughout the area
      without a clear somatotopic pattern. CONCLUSION: Stimulation-induced side effects
      in the PSA and its vicinity were difficult to attribute to certain anatomical
      areas as the same response was induced from various locations. Therefore, this
      study could not provide a meaningful somatotopic map with regard to stimulation
      induced side effects in the PSA.

PMID- 22608282
TI  - Physical and psychosocial predictors of functional trunk capacity in older adults
      with and without low back pain.
AB  - OBJECTIVE: The purpose of this study was to determine the physical and
      psychosocial predictors of functional trunk capacity in a group of healthy
      elderly individuals and a group of elderly patients with chronic low back pain
      (LBP). METHODS: The study was done in Canada and included 61 community-dwelling
      elderly individuals (29 patients with nonspecific chronic LBP and 32 healthy
      participants) who performed maximal trunk endurance and force tasks. Participants
      completed various psychologic and functional questionnaires. Sequential linear
      regression analyses were performed with functional capacity results (endurance
      and force) as dependent variables and questionnaire scores as independent
      variables. RESULTS: Endurance time and peak force were significantly lower in
      patients compared with healthy elderly individuals (all P values < .001), whereas
      pain-related fear of movement, pain catastrophizing, and depression levels were
      higher in patients than their healthy counterpart (all P values < .001). After
      adjusting for physical activity and disability levels (R(2) = 33.7%-50.5% in
      patients; R(2) = 0.1%-5.7% in healthy individuals), none of the psychologic
      questionnaire could explain variations observed in functional capacity in
      patients (R(2) changes, 4.8%-6.7%) and in healthy participants (R(2) changes,
      5.2%-10.6%). CONCLUSION: Patients showed diminished functional capacity compared
      with healthy participants. Moreover, physical activity levels represent the most
      important predictors of functional capacity in elderly patients with LBP.

PMID- 22608283
TI  - Anatomical association between wrist extensor musculature and topographical pain
      sensitivity maps of the elbow area.
AB  - OBJECTIVE: High-density topographical sensitivity maps have been developed to
      visualize nonuniformity deep tissue pain sensitivity in, for example, lateral
      epicondylitis (LE). The aim of this cadaveric study was to determine the
      anatomical association between the topographical sensitivity maps over the elbow
      area and wrist extensor musculature. METHODS: A topographical pressure
      sensitivity map consisting of 12 points forming a 3 * 4 matrix: 4 points in the
      superior part, 4 points in the middle, and 4 points in the lower part around the
      lateral epicondyle was marker on a 50-year embalmed cadaver. Color marker pins
      were inserted into each point. Pins were removed during the process of
      dissection, but the small holes created by their removal assured accurate
      relocation. RESULTS: Progressive dissection revealed that points 1 to 4 (superior
      line) were placed over the musculotendinous junction and belly of the extensor
      carpi radialis brevis (ECRB) muscle, points 6 to 8 (middle line) were placed over
      the musculotendinous junction and belly of the extensor digitorum communis
      muscle, and points 9 to 12 (inferior line) were located over the musculotendinous
      junction and belly of the extensor carpi ulnaris muscle. It was also observed
      that the superficial branch of the radial nerve runs between the belly of the
      ECRB and extensor digitorum communis muscles. CONCLUSIONS: This study confirmed
      that anatomical location previously assumed supporting the important wrist
      extensor muscles, particularly the ECRB, in patients with LE as depicted by
      pressure pain sensitivity maps. This study also suggests a potential role of the
      superficial branch of the radial nerve in LE.

PMID- 22608284
TI  - Descriptive anatomy of the interscalene triangle and the costoclavicular space
      and their relationship to thoracic outlet syndrome: a study of 60 cadavers.
AB  - OBJECTIVE: Thoracic outlet syndrome classically results from constrictions in 1
      or more of 3 specific anatomical locations: the interscalene triangle,
      costoclavicular space, and coracopectoral tunnel. Magnetic resonance and computed
      tomographic imaging studies suggest that, of the 3 potential locations for
      constriction, the costoclavicular space is the most susceptible to compression.
      This study of human cadavers aims to expand on the descriptive anatomy of the
      interscalene triangle and associated costoclavicular space. METHODS: The
      interscalene angle, interscalene triangle base, and costoclavicular space were
      measured on 120 sides of embalmed human cadavers. Linear distances and angles
      were measured using a caliper and protractor, respectively. The data were
      analyzed by calculating the mean, range, and standard deviation. RESULTS: The
      range for the interscalene base was 0 to 21.0 mm with a mean of 10.7 mm. For the
      interscalene angle, the range was 4 degrees  to 22 degrees  with a mean of 11.3
      degrees . Measurements for the costoclavicular space ranged from 6 to 30.9 mm
      with a mean of 13.5 mm. CONCLUSIONS: No significant differences were observed
      between left and right interscalene triangles or costoclavicular spaces;
      furthermore, there were no differences between the sexes concerning these 2
      locations.

PMID- 22608285
TI  - Association between the side of unilateral shoulder pain and preferred sleeping
      position: a cross-sectional study of 83 Danish patients.
AB  - OBJECTIVE: The purpose of this study was to evaluate if there is an association
      between the side of unilateral shoulder pain and the patient's preferred sleeping
      position and if the preferred sleeping position is related to which side of a
      double bed one lies in. METHODS: In a cross-sectional study, adult patients
      seeking chiropractic care with unilateral shoulder pain were asked about sleeping
      position and, if sleeping with a partner, which side of the bed they slept in. A
      total of 83 participants were included from 10 chiropractic clinics. Associations
      were cross-tabulated and tested by Fisher exact test. RESULTS: The pain was in
      the right shoulder in 55% (95 % confidence interval, 46-66) of the participants
      with unilateral pain. The side of shoulder pain was associated to the side
      patients slept on, with 67% of those sleeping on one side lying on the painful
      shoulder (P = .02). Moreover, patients were more likely to turn away from their
      partner at night, and 76% slept on the side opposite their partner (P < .001).
      CONCLUSIONS: Patients with unilateral shoulder pain were more likely to sleep on
      the side of the painful shoulder than on the pain-free side and reported to turn
      away from their partners in bed. It is unknown whether the observed associations
      are causal, but it is worth investigating whether a change in sleeping position
      has a positive effect on patients with shoulder pain and if this can be achieved
      simply by changing side of sleeping in bed.

PMID- 22608286
TI  - Assessment of the upper trapezius muscle temperature in women with and without
      neck pain.
AB  - OBJECTIVE: The purpose of the study was to analyze the upper trapezius muscle
      temperature using thermography in women with and without neck pain. METHODS:
      Thirty-six female university students were classified through the Neck Disability
      Index (NDI) into 2 groups: the neck pain group comprised 18 volunteers diagnosed
      with mild disability, and the control group, 18 healthy volunteers. All subjects
      were submitted to evaluation by thermography, which registered the skin surface
      temperature of the upper bilateral trapezius muscle. Student t test and Mann
      Whitney U test were used for the comparison between the groups, and the Spearman
      correlation coefficient was used for the appropriate correlations between the NDI
      score and the temperature values. A significance level of 5% was set. RESULTS: No
      significant difference was found between the groups regarding the temperature
      values of the upper left (P = .565) and right (P = .917) trapezius muscles, as
      well as in comparisons of temperature asymmetry (P = .542). In addition, no
      significant association was found between the study variables (P > .05).
      CONCLUSION: Women with neck pain, diagnosed with mild disability by NDI, did not
      present with reduction or asymmetry of upper trapezius muscle temperature when
      compared with a group without neck pain.

PMID- 22608287
TI  - Altered trapezius muscle behavior in individuals with neck pain and clinical
      signs of scapular dysfunction.
AB  - OBJECTIVE: The purpose of this study was to compare the behavior of the trapezius
      muscle in patients with chronic mechanical neck pain (MNP) and clinical signs of
      scapula dysfunction to healthy controls. METHODS: This is a cross-sectional,
      between-participant study of trapezius muscle behavior. Eighteen volunteers with
      chronic MNP and 20 healthy controls participated in the study. Participants
      performed isometric shoulder abduction, external rotation, and flexion at 3
      intensities of effort (maximum voluntary contraction [MVC], 50% MVC, and 20%
      MVC). Electromyographic signals were recorded unilaterally from the upper,
      middle, and lower portions of the trapezius muscle during isometric shoulder
      contractions. RESULTS: Significantly greater levels of lower trapezius
      electromyographic signals were observed in patients with MNP compared with
      controls for the abduction (P < .027) and external rotation (P < .036) conditions
      but not for the flexion condition (P > .392). No differences in activity were
      observed in the upper (P > .248) or middle (P > .052) portions of trapezius
      between groups during any of the isometric shoulder girdle conditions.
      CONCLUSIONS: These findings represent a change in the behavior of the lower
      trapezius muscle in individuals with MNP who exhibit clinical signs of scapular
      dysfunction. Clinicians should consider the potential involvement of the
      axioscapular muscles when assessing patients with chronic neck pain, as
      retraining scapular function may be required for the successful management of
      these patients.

PMID- 22608288
TI  - Spinous process hypertrophy associated with implanted devices in the external
      link model.
AB  - OBJECTIVE: Recent development of a chiropractic subluxation mimic, the external
      link model, uses titanium implants on lumbar vertebrae in the rat. The objective
      of this study was to evaluate potential correlations in the model between linking
      history, bone resorption, exudate formation, and experimentally induced
      intervertebral hypomobility. METHODS: Serial lateral radiographs of 73 male
      Sprague Dawley rats with implanted devices were reviewed. A baseline radiograph
      was obtained after a 6-week surgical recovery period, and a second radiograph was
      exposed after an 8-week hypomobility induction period. Spinous hypertrophy at the
      implant sites (L4, L5, and L6) was measured on the radiographs with a vernier
      caliper. Bone resorption and exudate build-up were assessed and compared with
      intervertebral hypomobility data previously collected. Data trends were described
      using cross-tabulated counts, analysis of variance, and regression analysis.
      RESULTS: Cross-tabulation suggested differences between hypomobility-induced rats
      and control rats. However, correlation analysis showed no predictive role for
      spinous hypertrophy relative to intervertebral mobility. Similarly, exudate level
      did not predict spinous hypertrophy. However, implant presence and vertebral
      level had a significant interaction, with moderate and severe hypertrophy
      occurring more frequently at L4 and L6 in hypomobility-induced rats. Age did not
      materially influence spinous hypertrophy. CONCLUSIONS: Mechanical stresses
      produced at the implant bone interface in rats with induced hypomobility
      contribute to spinous hypertrophy beyond that simply due to the presence of the
      implants. However, spinous hypertrophy does not contribute significantly to
      intervertebral hypomobility in the external link model.

PMID- 22608289
TI  - An evaluation of aerobic and anaerobic composting of banana peels treated with
      different inoculums for soil nutrient replenishment.
AB  - This study sought to evaluate the efficacy of aerobic and anaerobic composting of
      inoculated banana peels, and assess the agronomic value of banana peel-based
      compost. Changes in the chemical composition under aerobic and anaerobic
      conditions were examined for four formulations of banana peel-based wastes over a
      period of 12 weeks. The formulations i.e. plain banana peel (B), and a mixture
      with either cow dung (BC), poultry litter (BP) or earthworm (BE) were separately
      composted under aerobic and anaerobic conditions under laboratory conditions.
      Inoculation with either cow dung or poultry litter significantly facilitated
      mineralization in the order: BP>BC>B. The rate of decomposition was significantly
      faster under aerobic than in anaerobic composting conditions. The final composts
      contained high K (>100 g kg(-1)) and TN (>2%), indicating high potential as a
      source of K and N fertilizer.

PMID- 22608290
TI  - Membrane bioreactor and nanofiltration hybrid system for reclamation of municipal
      wastewater: removal of nutrients, organic matter and micropollutants.
AB  - A membrane bioreactor (MBR) and nanofiltration (NF) hybrid system was
      investigated to demonstrate the performance of treating nitrogen, phosphorus and
      pharmaceuticals and personal care products (PPCPs) in municipal wastewater. With
      the MBR and NF (molecular weight cut off (MWCO): 210 Da), the concentration of
      total nitrogen (TN) and total phosphorus (TP) was effectively reduced by
      nitrification by MBR and negatively charged surface of NF (TN: 8.67 mgN/L and TP:
      0.46 mgP/L). Biosorption and microbial decomposition in MBR seem to be major
      removal mechanisms for the removal of PPCPs. Among various parameters affecting
      the removal of PPCPs by NF, namely, physicochemical properties of the PPCPs
      (charge characteristics, hydrophobicity and M(W)) and membranes (MWCO and surface
      charge), the MWCO effect was found to be the most critical aspect.

PMID- 22608291
TI  - Novel Chlamydiaceae disease in captive salamanders.

PMID- 22608292
TI  - Synthesis, characterization and quantum chemical ab initio calculations of new
      dimeric aminocyclodiphosph(V)azane and its Co(II), Ni(II) and Cu(II) complexes.
AB  - The complexes of type [M(2)LCl(2)] in which M=Co(II), Ni(II) and Cu(II) ions and
      L are 1,3-o-pyridyl-2,4-dioxo-2',4'-bis(3-benzo[d]thiazol-2-yl-2-iminothiophene)
      cyclodiphosph(V)azane, were prepared and their structures were characterized by
      different physical techniques (IR, UV-Vis, (1)H NMR, (31)P NMR, mass, TGA, DTA,
      XRD, SEM, magnetic moment and electrical conductance measurements). Ab initio
      calculations at the level of DFT B3LYP/6-31G(d) were utilized to find the optimum
      geometry of the ligand. Spectral characterization of the ligand was simulated
      using DT-DFT method. Infrared spectra of the complexes indicate deprotonation and
      coordination of the imine NH. It also confirms that nitrogen atoms of the
      pyridine group and thiazole group contribute to the complexation. NBO natural
      charges were computed and discussed in the light of coordination centers.
      Electronic spectra and magnetic susceptibility measurements as well as quantum
      chemical calculations reveal square planar geometry for Cu(II) and Ni(II)
      complexes and tetrahedral geometry for Co(II) complex. The elemental analyses and
      mass spectral data have justified the M(2)LCl(2) composition of complexes.

PMID- 22608293
TI  - Margin convergence anchorage to bone for reconstruction of the anterior
      attachment of the rotator cable.
AB  - PURPOSE: The purpose of this study was to compare the biomechanical
      characteristics of a massive L-shaped retracted rotator cuff tear repaired with
      either soft-tissue side-to-side sutures or margin convergence anchorage to bone.
      METHODS: Eight matched pairs of cadaveric shoulders were used. The supraspinatus
      and infraspinatus were secured in a clamp at 30 degrees  of glenohumeral
      abduction. The subscapularis was secured in a separate clamp, and a constant load
      was applied. A massive L-shaped rotator cuff tear of the supraspinatus and
      infraspinatus tendon was created. In all specimens the posterior aspect of the
      tear was repaired by a transosseous-equivalent technique. In 1 group we placed 2
      margin convergence sutures between the supraspinatus and the rotator interval. In
      the comparison group, a suture anchor was inserted at the anterior attachment of
      the rotator cable. Margin convergence anchorage to bone was then performed
      between the supraspinatus and the rotator interval. Each specimen was tested with
      an Instron machine (Instron, Canton, MA) and a video digitizing system. A paired
      t test was used for statistical analysis. RESULTS: Margin convergence anchorage
      to bone decreased gap formation at cycle 1, cycle 30, and yield load across the
      entire footprint (P < .05). In both constructs the anterior gap was greater than
      the posterior gap at cycle 1, cycle 30, and yield load (P < .05). Margin
      convergence anchorage to bone decreased hysteresis and increased stiffness during
      the first cycle and increased yield load (P < .05). CONCLUSIONS: Using margin
      convergence anchorage to bone to restore the anterior attachment of the rotator
      cable decreased gap formation across the entire footprint and improved
      biomechanical properties for cycle 1 and yield load compared with soft-tissue
      margin convergence for massive rotator cuff repairs. CLINICAL RELEVANCE:
      Repairing the anterior rotator cuff with margin convergence anchorage to bone may
      improve clinical outcomes of an L-shaped massive tear repair.

PMID- 22608294
TI  - Comparative hospital cost-analysis of open and robotic-assisted radical
      prostatectomy.
AB  - OBJECTIVE: To perform a contemporary comparative cost-analysis of robotic
      assisted laparoscopic radical prostatectomy (RARP) and open radical retropubic
      prostatectomy (RRP). METHODS: All patients undergoing RARP (n = 115) or RRP (n =
      358) by 1 of 4 surgeons at a single institution during a 15-month period were
      retrospectively reviewed. The hospital length of stay (LOS), operative time,
      hospital charges, reimbursement, and direct and indirect hospital costs were
      analyzed and compared. RESULTS: The mean LOS between patients undergoing RARP
      (1.2 +/- 0.6 days) and RRP (1.4 +/- 0.8 days) was not significantly different.
      The operating room supply costs per case were almost 7 times greater for RARP
      ($2852 +/- $528) than for RRP ($417 +/- $59; P < .05). The ancillary, cardiology,
      imaging, administrative, laboratory, and pharmacy costs were not significantly
      different between the 2 approaches. The mean total costs per case for RARP
      exceeded the total costs for RRP by 62% ($14 006 +/- $1641 vs $8686 +/- $1989; P
      < .05). Payment to the hospital from all sources was nearly equivalent: $10 011
      for RRP and $9993 for RARP. Therefore, the average profit for each RRP was $1325
      and each RARP lost $4013. CONCLUSION: In the present single-institution analysis,
      the total actual costs associated with RARP were significantly greater than those
      for RRP and were attributable to the robotic equipment and supplies.

PMID- 22608295
TI  - Cimicifuga racemosa and its triterpene-saponins prevent the Metabolic Syndrome
      and deterioration of cartilage in the knee joint of ovariectomized rats by
      similar mechanisms.
AB  - PURPOSE: An unphysiologic accumulation of fat cells in many parts of the body
      including abdomen and joints results in increased production of pro-inflammatory
      cytokines which have adverse effects on serum lipids, glucose and on joint
      cartilage. The special extract of Cimicifuga racemosa CR BNO 1055 was shown to
      reduce the size of the abdominal fat depot. It was therefore tempting to test
      whether this extract, its saponin and its unpolar and polar fractions S- and R
      fraction respectively (no quotation) also reduce fat depots and fat cell
      accumulation in a fat depot located in the lower hind leg (called paratibial fat
      depot = PFD), in joint fat pads (in the knee joint this is called Hoffa's fat
      pad) that occur in response to ovariectomy and whether this was accompanied by
      reduced serum lipids, glucose and improved cartilage features in the knee joint.
      METHODS: Rats (n = 10/group) were ovariectomized (ovx) and fed with CR BNO 1055,
      S- or R-fraction containing food (average intake 8.2, or 2.05 or 7.07
      mg/day/animal) for 4 weeks. Ovx rats kept under no additive-containing food
      served as controls. The sizes of the PFD, of Hoffa's fat pad and of the cartilage
      thickness of the knee joints were determined by quantitative computer tomography
      and histomorphometrically. In the serum cholesterol, leptin and glucose levels
      were measured. RESULTS: High load with fat tissue in the PFD and in the knee
      joints was present in the ovx rats. Treatment with CR BNO 1055 and its S-fraction
      reduced fat load of both, Hoffa's fat pad and of the PFD significantly and this
      resulted in reduced body weight which was significant under CR BNO 1055. Fat load
      in the PFD correlated significantly with the height of serum leptin and
      cholesterol. The fat load in the knee joint correlated inversely with the size of
      knee cartilage tissue. CONCLUSIONS: High fat load of the body increases following
      ovx and this causes increased serum leptin, cholesterol and glucose levels.
      Following ovx the size of Hoffa's fat pad increases also significantly and this
      has adverse effects on knee cartilage tissue. Therefore, increased fat tissue in
      joints appears to belong to the Metabolic Syndrome. This effect can be largely
      prevented by CR BNO 1005 and its S- but not by its R-fraction. Hence, the
      saponins in CR BNO 1055 may be useful in preventing the Metabolic Syndrome and
      osteoarthritis.

PMID- 22608297
TI  - Clozapine resistance--augmentation strategies.

PMID- 22608296
TI  - Blood basophils from cystic fibrosis patients with allergic bronchopulmonary
      aspergillosis are primed and hyper-responsive to stimulation by aspergillus
      allergens.
AB  - INTRODUCTION: Fifteen to sixty percent of cystic fibrosis patients harbor
      Aspergillus fumigatus (Af) in their airways (CF-AC) and some will develop
      allergic bronchopulmonary aspergillosis (CF-ABPA). Since basophils play a key
      role in allergy, we hypothesized that they would display alterations in CF-ABPA
      patients compared to CF-AC or patients without Af colonization (CF). METHODS:
      Using flow cytometry, we measured CD203c, CD63 and CD123 levels on basophils from
      CF-ABPA (N=11), CF-AC (N=14), and CF (N=12) patients before and after ex vivo
      stimulation with Af allergens. RESULTS: Baseline CD203c was increased in
      basophils from CF-ABPA compared to CF-AC and CF patients. Af extract and
      recombinant Aspf1 stimulated basophils from CF-ABPA patients to markedly
      upregulate CD203c, along with modest upregulation of CD63 and a CD123 downward
      trend. Plasma TARC/CCL17 at baseline and post-stimulation cell supernatant
      histamine levels were similar in the three groups. CONCLUSIONS: In CF-ABPA, blood
      basophils are primed and hyperresponsive to Af allergen stimulation.

PMID- 22608298
TI  - Placebo, a historical perspective.
AB  - Substances and interventions with no specific therapeutic effect have been in use
      since the dawn of history. The term placebo has first been mentioned in the
      Scriptures, but it was not until the 19th century that it appeared in a medical
      context. Although lay people like Voltaire, and physicians such as Sir William
      Osler, have raised the possibility that much of what physicians did had no
      specific therapeutic effect, this notion was not shared by the public at large or
      by the medical profession. It was only by the end of the 18th century that a
      placebo-controlled trial has been conducted, repudiating the therapeutic effect
      of mesmerism. The advent, in the late 1940s, of effective treatments, which also
      had serious adverse effects, made the distinction between placebo and putative,
      active drug effects more relevant and urgent, and cleared the way for double
      blind, randomized, placebo-controlled trials. This in turn triggered an ethical
      debate on the use of placebo, both in research and in clinical practice.
      Anthropologists, sociologists, physiologists, and medical researchers are all
      focusing their efforts on understanding the mechanism, role and modulating
      factors of placebo.

PMID- 22608299
TI  - Estimation of the economical effects of Eimeria infections in Estonian dairy
      herds using a stochastic model.
AB  - In this study, a stochastic predictive model stimulating a constant infection
      pressure of Eimeria was used to estimate production outcome, economic, and
      effects of treatment decisions in a dairy herd of 100 cows. The intestinal
      parasite cause problems mainly in calves, and is known to have long term effects
      on the growth rate, and in severe cases can result in mortalities. Due to the
      inconspicuous nature of the parasite, the clinical signs and sub-clinical
      manifestations it may produce can be overlooked. Acquired data from literature
      and Estonian dairy farms were implemented in the SimHerd IV model to simulate
      three scenarios of symptomatic treatment: no calves treated (NT), default
      estimate of the current treatment strategy (DT), and all calves treated (AT).
      Effects of metaphylactic treatment were studied as a lowering of the infection
      pressure. Delay in the age for beginning of insemination of heifers was the
      effect with the largest economic impact on the gross margin, followed by calf
      mortality and reduction in growth rate. Large expenses were associated with the
      introduction of replacement heifers and feeding of heifers as a result of the
      delay in reaching a specific body weight at calving. Compared to the control
      scenarios, with no effects and treatments of Eimeria, dairy farmers were
      estimated to incur annual losses ranging 8-9% in the balanced income. Providing
      metaphylactic drugs resulted in an increased gross margin of 6-7%. Purchase of
      new heifers compensated for some production losses that would otherwise have
      enhanced expenses related to Eimeria. The simulation illustrates how effects of
      Eimeria infections can have long lasting impact on interacting management
      factors. It was concluded that all three simulated symptomatic treatment regimes
      provided only small economic benefits if they were applied alone and not in
      combination with lowering of infection pressure.

PMID- 22608300
TI  - [Pulmonary thromboembolism secondary to intrapulmonary inferior vena cava filter
      migration].

PMID- 22608301
TI  - [Total external ophthalmoplegia due to phenytoin].

PMID- 22608302
TI  - Outcome of tracheotomized patients following reintubation.
AB  - OBJECTIVE: To evaluate the outcome of tracheotomized patients after reintubation.
      METHOD: Secondary analysis from a prospective, multicenter and observational
      study including 36 Intensive Care Units (ICUs) from 8 countries. PATIENTS: A
      total of 180 patients under mechanical ventilation for more than 48 hours,
      extubated and reintubated within 48 hours. INTERVENTIONS: None. OUTCOMES: ICU
      mortality, length of ICU stay, organ failure. RESULTS: Fifty-two patients (29%)
      underwent tracheotomy after reintubation. The median time from reintubation to
      tracheotomy was 2.5 days (interquartile range (IQR) 1-8 days). The length of ICU
      stay was significantly longer in the tracheotomy group compared with the group
      without tracheotomy (median time 25 days, IQR 17-43 versus 16.5 days (IQR 11-25);
      p<0.001). ICU mortality in the tracheotomy group was not significantly different
      (31% versus 27%; p 0.57). CONCLUSIONS: In our cohort of reintubated patients,
      tracheotomy is a common procedure in the ICU. Patients with tracheotomy had an
      outcome similar to those without tracheotomy.

PMID- 22608303
TI  - Withdrawal syndrome in the pediatric intensive care unit. Incidence and risk
      factors.
AB  - OBJECTIVE: To determine the incidence of withdrawal syndrome after prolonged
      infusion of fentanyl and midazolam in children, and the associated risk factors.
      DESIGN: Historic or retrospective cohort study. SETTING: Pediatric Intensive Care
      Unit in an academic center. PATIENTS: Forty-eight pediatric patients who received
      sedation and analgesia only with fentanyl and midazolam through continuous
      infusion for at least 48 hours. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST:
      Collected data included demographic and clinical parameters, dose and duration of
      sedation received, and incidence, severity and treatment of withdrawal syndrome.
      RESULTS: Fifty percent of the patients developed withdrawal syndrome. There were
      significant differences between the patients who developed withdrawal syndrome
      and those who did not, in terms of the duration of infusion and the cumulative
      doses of both drugs. A cumulative fentanyl dose of 0.48 mg/kg, a cumulative
      midazolam dose of 40 mg/kg, and a duration of infusion of both drugs of 5.75 days
      were risk factors for the development of withdrawal syndrome. Most children
      developed mild or moderate disease, beginning about 12-36 hours after weaning
      from infusion. Methadone was used in most cases for treating withdrawal.
      CONCLUSIONS: There is a high incidence of withdrawal syndrome in children
      following the continuous infusion of midazolam and fentanyl. The duration of
      infusion of both drugs and higher cumulative doses are associated with the
      development of withdrawal syndrome.

PMID- 22608304
TI  - Marketing foods to children through product packaging: prolific, unhealthy and
      misleading.
AB  - OBJECTIVE: To investigate marketing techniques used on the packaging of child
      oriented products sold through supermarkets. DESIGN: Food and beverage products
      which met criteria for 'marketed to children' were recorded as child-oriented.
      The products were analysed for food categories, nutritional value, and type and
      extent of marketing techniques used. SETTING: A major supermarket chain in
      Adelaide, South Australia. SUBJECTS: Child-oriented food and beverage products.
      RESULTS: One hundred and fifty-seven discrete products were marketed to children
      via product packaging; most (75.2 %) represented non-core foods, being high in
      fat or sugar. Many marketing techniques (more than sixteen unique marketing
      techniques) were used to promote child-oriented food products. Claims about
      health and nutrition were found on 55.5 % of non-core foods. A median of 6.43
      marketing techniques per product was found. CONCLUSIONS: The high volume and
      power of marketing non-core foods to children via product packaging in
      supermarkets should be of concern to policy makers wanting to improve children's
      diet for their health and to tackle childhood obesity. Claims about health or
      nutrition on non-core foods deserve urgent attention owing to their potential to
      mislead and confuse child and adult consumers.

PMID- 22608305
TI  - A celebration of Franco-Argentinean neuroscience.

PMID- 22608306
TI  - Ultrastructure of the distal retina of the adult zebrafish, Danio rerio.
AB  - The organization, morphological characteristics, and synaptic structure of
      photoreceptors in the adult zebrafish retina were studied using light and
      electron microscopy. Adult photoreceptors show a typical ordered tier arrangement
      with rods easily distinguished from cones based on outer segment (OS) morphology.
      Both rods and cones contain mitochondria within the inner segments (IS),
      including the large, electron-dense megamitochondria previously described (Kim et
      al.) Four major ultrastructural differences were observed between zebrafish rods
      and cones: (1) the membranes of cone lamellar disks showed a wider variety of
      relationships to the plasma membrane than those of rods, (2) cone pedicles
      typically had multiple synaptic ribbons, while rod spherules had 1-2 ribbons, (3)
      synaptic ribbons in rod spherules were ~2 times longer than ribbons in cone
      pedicles, and (4) rod spherules had a more electron-dense cytoplasm than cone
      pedicles. Examination of photoreceptor terminals identified four synaptic
      relationships at cone pedicles: (1) invaginating contacts postsynaptic to cone
      ribbons forming dyad, triad, and quadrad synapses, (2) presumed gap junctions
      connecting adjacent postsynaptic processes invaginating into cone terminals, (3)
      basal junctions away from synaptic ribbons, and (4) gap junctions between
      adjacent photoreceptor terminals. More vitread and slightly farther removed from
      photoreceptor terminals, extracellular microtubule-like structures were
      identified in association with presumed horizontal cell processes in the OPL.
      These findings, the first to document the ultrastructure of the distal retina in
      adult zebrafish, indicate that zebrafish photoreceptors have many characteristics
      similar to other species, further supporting the use of zebrafish as a model for
      the vertebrate visual system.

PMID- 22608307
TI  - Histochemical characterization of the mucins of the alimentary tract of the grass
      snake, Natrix natrix (Colubridae).
AB  - Characterization of mucins in the alimentary tract of the grass snake, Natrix
      natrix was performed by histochemical (PAS, Alcian Blue, pH 2.5 and pH 1.0,
      sialidase-Alcian Blue, pH 2.5, HID-AB pH 2.5) and lectin-histochemical (WGA,
      SWGA, PNA, sialidase-PNA, SBA, sialidase-SBA, DBA, sialidase-DBA, ConA, BSI-B4,
      AAA, UEA-1, LTA) techniques. Oesophageal lining epithelium consisted of ciliated
      and goblet cells, with no pluricellular glands. Mannosylated sialosulfomucins
      were observed. Fundic mucosa of stomach presented surface cells producing
      sialomucins with terminal sialic acid linked to galactose. In gastric glands neck
      and oxynticopeptic cells were found. Neck cells had sialomucins with mannose, N
      acetylglucosamine, galactose, N-acetylgalactosamine and fucose-alpha-(1,2)-linked
      residues. Cytoplasm of oxynticopeptic cells showed N-acetylgalactosamine and
      fucose residues. Secretion of surface cells in pyloric mucosa was similar to that
      of fundic ones, differing in having fucose. Goblet cells in the small intestine
      of N. natrix produced sulfo- and sialomucins, with sialic acid linked to
      galactose and N-acetylgalactosamine residues. Mucins also presented residues of
      mannose. Goblet cells in the large intestine presented sulfomucins only, with
      terminal N-acetylgalactosamine, galactose and N-acetylglucosamine. The
      glycosylation patterns found are probably related to protection against injuries,
      gastric juice and microorganisms, both pathogenic and decomposers, as well as to
      dietary adaptations.

PMID- 22608308
TI  - Existence of serotonin and neuropeptides-immunoreactive endocrine cells in the
      small and large intestines of the mole-rats (Spalax leucodon).
AB  - The present study was conducted to clarify the regional distribution and relative
      frequency of endocrine cells secreting serotonin, substance P (SP),
      cholecystokinin-8 (CCK-8), vasoactive intestinal polypeptide (VIP) and
      neurotensin in the small and large intestine of the mole-rats (Spalax leucodon),
      by specific immunohistochemical methods. In the small and large intestine of mole
      rats (Spalax leucodon), serotonin, SP and VIP were identified with various
      frequencies, but CCK-8 and neurotensin were not observed. Most of the IR cells in
      the small and large intestine were located in the intestinal crypt and epithelium
      however, they were more frequency in the intestinal crypt. Serotonin-IR cells
      were detected throughout the whole intestinal tract, predominantly in the
      duodenum and colon. SP-IR cells were demonstrated throughout the whole intestinal
      tract except for the ileum and rectum with highest frequencies in the cecum. VIP
      IR cells were found in all parts of the small intestine except for the large
      intestine. In conclusion, the general distribution patterns and relative
      frequency of intestinal endocrine cells of the mole-rats (Spalax leucodon) was
      similar to those of some rodent species. However, some species-dependent unique
      distributions and frequencies characteristics of endocrine cells were also
      observed in the present study.

PMID- 22608309
TI  - Changes in the apoptotic gene expression profile in CLL patients treated with
      rituximab combined with cladribine and cyclophosphamide-preliminary results.
AB  - The study was aimed to investigate modifications of apoptotic gene expression
      profile by microarray technique in 10 patients with chronic lymphocytic leukemia
      by treatment with rituximab, cladribine and cyclophosphamide (RCC) according to
      IGHV mutational status. The TaqMan Low Density Array for 96 gene transcripts was
      used. Those modifications followed two distinctive patterns largely overlapping
      the IGHV mutational status. In the IGHV-mutated group, the expression of many
      proapoptotic genes increased after treatment as compared to initial value. Our
      results suggest that RCC drugs may act through influence on the expression of
      some apoptosis-involved genes dependently on the IGVH mutational status.

PMID- 22608310
TI  - Efficacy of hypomethylating agents in therapy-related myelodysplastic syndromes.
AB  - We retrospectively assessed morphologic and cytogenetic responses to 5
      azacytidine and decitabine in a cohort of 42 adult therapy-related
      myelodysplastic syndromes (tMDS) patients treated at Memorial Sloan-Kettering
      Cancer Center and in 2 industry-sponsored decitabine trials (D0007 and DACO-020).
      The overall response rate (complete remission+marrow CR+hematologic improvement)
      was 38%, including 6 patients with complete remission (14%), 6 with marrow CR
      with or without hematologic improvement (14%), and 4 with hematologic improvement
      alone (10%). We conclude that DNA methyltransferase inhibitors showed activity in
      tMDS that is roughly comparable to that seen in de novo MDS.

PMID- 22608311
TI  - Rescue human chorionic gonadotropin for false empty follicle syndrome: optimism
      for successful pregnancy outcome.
AB  - OBJECTIVE: To describe two cases of successful pregnancy after a rescue course of
      hCG in the setting of false empty follicle syndrome. DESIGN: Case report.
      SETTING: Academic medical center. PATIENT(S): Two patients undergoing ultrasound
      guided oocyte retrieval with failure to obtain oocytes during oocyte retrieval.
      INTERVENTION(S): Rescue course of hCG with second oocyte retrieval 35 hours
      later. MAIN OUTCOME MEASURE(S): Live birth. RESULT(S): Two live-birth
      pregnancies. CONCLUSION(S): Live-birth pregnancies are a realistic possibility
      after administration of a rescue course of hCG and repeat oocyte retrieval in the
      setting of false empty follicle syndrome.

PMID- 22608312
TI  - Expression of phosphoinositide-specific phospholipase C enzymes in normal
      endometrium and in endometriosis.
AB  - OBJECTIVE: To delineate the panel of expression of phosphoinositide-specific
      phospholipase C (PI-PLC) signaling enzymes in normal endometrium and in
      endometriosis. DESIGN: Clinical/experimental study. SETTING: University.
      PATIENT(S): Healthy donor woman and endometriosis-affected woman.
      INTERVENTION(S): Normal endometrium and endometriosis surgical biopsies were
      analyzed using gene expression analyses methodology (reverse transcriptase
      polymerase chain reaction [PCR], bioanalyses). MAIN OUTCOME MEASURE(S): Gene
      expression (messenger RNA concentration) measures of 12 PI-PLC enzymes: PI-PLC
      beta1, PI-PLC beta2, PI-PLC beta3, PI-PLC beta4, PI-PLC gamma1, PI-PLC gamma2, PI
      PLC delta1, PI-PLC delta3, PI-PLC delta4, PI-PLC epsilon, PI-PLC eta1, and PI-PLC
      eta2. RESULT(S): PI-PLC beta1, PI-PLC beta3, PI-PLC delta1, and PI-PLC delta3
      enzymes were detected, although differently expressed in normal and endometriosis
      tissues. CONCLUSION(S): The involvement of PI-PLC enzymes in inflammation and the
      consistency of susceptible endometriosis loci with PI-PLC genes mapping
      corroborate the hypothesis that PI signaling might be involved in the
      pathogenesis of endometriosis.

PMID- 22608313
TI  - Inhibitory effects of methotrexate on spontaneous motility and Cajal-like type of
      tubal interstitial cells in rabbit oviduct.
AB  - OBJECTIVE: To study the adverse biomechanical effects of methotrexate (MTX) on
      spontaneous tubal motility and on a widely distributed Cajal-like type of tubal
      interstitial cells (t-ICC) in rabbits. In our previous study, MTX was confirmed
      to cause acute endosalpingitis, and ultrastructural and steroid receptor damage
      in rat's endosalpinx in a dose-dependent manner. DESIGN: Differences in
      spontaneous tubal contractions and cellular distribution of t-ICC in isthmus were
      evaluated in response to MTX. SETTING: Medical school research laboratory.
      ANIMAL(S): Twenty nonpregnant female New Zealand albino rabbits in estrus stage
      were divided equally into four groups. INTERVENTION(S): Rabbits received IM MTX
      (1, 5, 10 mg/kg body weight) and controls received physiological saline. MAIN
      OUTCOME MEASURE(S): On day 7, in vitro motility studies measuring spontaneous
      tubal contractions were performed, and cellular distribution of t-ICC was
      determined by immunohistochemistry. RESULT(S): Methotrexate produced a
      concentration-dependent inhibition of spontaneous isthmus contractions (frequency
      in 5, 10 mg/kg groups, and amplitude in 1, 5, 10 mg/kg MTX groups). It decreased
      significantly compared with the control group. Meanwhile, MTX at 5, 10 mg/kg
      decreased the population of c-kit immunoreactive t-ICC significantly.
      CONCLUSION(S): The decreased t-ICC may contribute to the diminished tubal smooth
      muscle contractility caused by MTX as observed. Tubal interstitial cells might be
      new potential targets for a variety of dysfunctional tubal motility diseases.

PMID- 22608314
TI  - Spermatogonial stem cell preservation in boys with Klinefelter syndrome: to bank
      or not to bank, that's the question.
AB  - Although early development of testis appears normal in boys with Klinefelter
      syndrome (KS), spermatogonial stem cell (SSC) depletion occurs in midpuberty,
      leading to infertility. Therefore, freezing of semen samples or testicular tissue
      sampling could be offered to boys with KS at onset of puberty. However, only in
      about half of patients with KS, adult or prepubertal, spermatozoa or SSCs can be
      observed, and to date, no clinical parameters are available to detect patients
      who might benefit from these techniques. Furthermore, strategies for the further
      use of the cryopreserved material are still under investigation. Retrieval of
      spermatogonial cells in prepubertal boys with KS should therefore still be viewed
      as experimental and patients and their parents must be counseled accordingly.

PMID- 22608315
TI  - Is the zona pellucida thickness of human embryos influenced by women's age and
      hormonal levels?
AB  - OBJECTIVE: To evaluate whether zona pellucida thickness (ZPT) of human embryos is
      correlated with maternal age, patient's hormonal status, embryo quality, and IVF
      outcomes. DESIGN: Prospective study. SETTING: University-affiliated IVF clinic.
      PATIENT(S): Couples undergoing IVF-ET cycles. INTERVENTION(S): Zona measurements,
      clinical data collection. MAIN OUTCOME MEASURE(S): Correlation between the ZPT
      and maternal age, basal FSH and E(2) levels, stimulation protocols, cause of
      infertility, embryo quality, and implantation/pregnancy rates. RESULT(S): The
      measurements of ZPT were collected from 5,184 day 3 human embryos originated from
      744 IVF patients. The overall mean ZPT was 16.18 +/- 2.00 MUm. No significant
      correlation was observed between the ZPT and the patient's age, E(2) values on
      the day of hCG administration, basal concentration of serum FSH, stimulation
      protocol, infertility diagnosis, and implantation/pregnancy rates. The ZPT was
      strongly influenced only by the embryo quality: Embryos with good morphology
      exhibited considerably thinner ZP compared with those of less favorable
      morphology (mean 15.87 +/- 2.48 MUm vs. 16.36 +/- 2.57 MUm, respectively). The
      ZPT had no significant impact on the implantation and pregnancy rates.
      CONCLUSION(S): The thickness of the human ZP of day 3 embryos is not influenced
      by women's age and hormonal levels. The strong correlation between ZPT and embryo
      quality suggests that thickness of ZP depends on inherent embryo properties. The
      overall ZPT is not a good predictive indicator for IVF clinical outcomes.

PMID- 22608317
TI  - Frozen-thawed spermatozoa from oligozoospermic ejaculates are susceptible to in
      situ DNA fragmentation in polyvinylpyrrolidone-based sperm-immobilization medium.
AB  - OBJECTIVE: To elucidate the effect of sperm immobilization media that are and are
      not based on polyvinylpyrrolidone (PVP) on the DNA integrity of fresh and frozen
      thawed spermatozoa during standard intracytoplasmic sperm injection (ICSI)
      conditions. DESIGN: Experimental prospective study. SETTING: Embryology research
      laboratory. PATIENT(S): Forty-six ejaculates from normozoospermic and
      oligozoospermic men. INTERVENTION(S): Assessment of sperm DNA fragmentation by
      single-cell gel electrophoresis assay. MAIN OUTCOME MEASURE(S): DNA integrity of
      fresh and frozen-thawed spermatozoa from normozoospermic and oligozoospermic
      ejaculates exposed to PVP-based and non-PVP-based media. RESULT(S): Exposure of
      fresh and frozen thawed spermatozoa from normozoospermic and oligozoospermic
      ejaculates to PVP-based medium in an ICSI dish for 30 minutes statistically
      significantly increased the DNA fragmentation. In contrast, the extent of DNA
      fragmentation in non-PVP-based medium did not statistically significantly differ
      from control. CONCLUSION(S): A PVP-based medium can induce a statistically
      significant amount of sperm DNA fragmentation in an ICSI dish, and frozen-thawed
      sperm from oligozoospermic ejaculates are more susceptible to in situ DNA
      fragmentation.

PMID- 22608316
TI  - Oocyte vitrification does not increase the risk of embryonic aneuploidy or
      diminish the implantation potential of blastocysts created after intracytoplasmic
      sperm injection: a novel, paired randomized controlled trial using DNA
      fingerprinting.
AB  - OBJECTIVE: To assess the impact of oocyte vitrification on aneuploidy and
      reproductive potential by comparing vitrified and control oocytes from a single
      patient within a single cycle and a single fresh transfer. DESIGN: Paired
      randomized controlled trial in which each patient's cohort of mature oocytes was
      divided into two even groups with half undergoing Cryotop vitrification and rapid
      warming and half serving as controls. SETTING: Academic center for reproductive
      medicine. PATIENT(S): Forty-four patients with a mean age of 29.9 +/- 2.3 years
      and normal ovarian reserve. INTERVENTION(S): Cryotop vitrification of half of
      mature oocytes. Trophectoderm biopsy with single nucleotide polymorphism
      microarray analysis for ploidy and DNA fingerprinting. MAIN OUTCOME MEASURE(S):
      Rate of aneuploidy (primary outcome), fertilization, cleavage, blastulation, and
      implantation in embryos derived from vitrified and control oocytes. RESULT(S): A
      total of 588 mature oocytes were randomized, with 240/294 (81.6%) surviving
      vitrification. Among surviving vitrified oocytes, there was a lower fertilization
      rate with intracytoplasmic sperm injection (77.9% vs. 90.5%; relative risk [RR],
      0.86; 95% confidence interval [CI], 0.80-0.93), a lower cleavage rate (90.9% vs.
      99.2%; RR, 0.92; 95% CI, 0.87-0.96), and a lower usable blastocyst formation rate
      per two pronuclei (34.8% vs. 50.8%; RR, 0.68; 95% CI, 0.54-0.86). There was no
      difference in the rate of embryonic aneuploidy (vitrified, 29.1% vs. control,
      26.4%). In paired blastocyst transfers, the ongoing pregnancy rate per embryo
      transferred was similar (vitrified, 53.9% vs. control, 57.7%). CONCLUSION(S):
      Although the IVF process is less efficient after oocyte vitrification,
      implantation rates are equivalent and there is no increased risk of aneuploidy.
      Given the lack of other viable options, this study provides great reassurance to
      patients and clinicians applying oocyte vitrification for fertility preservation.

PMID- 22608318
TI  - Maternal characteristics and twin gestation outcomes over 10 years: impact of
      conception methods.
AB  - OBJECTIVE: To compare maternal characteristics and obstetric outcomes of
      spontaneously conceived (SC) and after-fertility treatment (FT) twins. DESIGN:
      Retrospective study. SETTING: Single tertiary center (university hospital).
      PATIENT(S): All twin pregnancies (n = 1,239) delivered >= 24 weeks of gestation
      and classified by the mode of conception. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Maternal age, prematurity, preterm rupture of membranes (PROM),
      delivery mode, cervical insufficiency, preeclampsia/HELLP (hemolysis, elevated
      liver enzymes, low platelet count) syndrome, gestational diabetes, and postpartum
      hemorrhage. RESULT(S): Of 1,239 mothers evaluated, 34.4% received FT. We observed
      a continuous 3.2-year mean increase in maternal age over time in the FT
      population. The FT group had statistically significantly higher rates of women >=
      35 years of age versus the SC group (37.6% vs. 22.9%). Mean maternal age (32.5
      vs. 30.1 years) and the rates of cesarean delivery (72.3% vs. 63.9%), dichorionic
      twin prematurity (67.7% vs. 59.6%), postpartum hemorrhage (9.9% vs. 6%), PROM
      (2.3% vs. 0.6%), and cervical insufficiency (17.6% vs. 10%) were statistically
      significantly higher in the FT group. Preeclampsia/HELLP syndrome and gestational
      diabetes showed no significantly significant difference. CONCLUSION(S): Mothers
      of twins after FT were statistically significantly older and had higher rates of
      prematurity, cesarean delivery, and obstetric morbidity.

PMID- 22608320
TI  - Chronic disease management in ageing populations.

PMID- 22608319
TI  - Metformin: direct inhibition of rat ovarian theca-interstitial cell
      proliferation.
AB  - OBJECTIVE: To determine whether metformin has direct effects on ovarian theca
      interstitial (T-I) cell proliferation through activation of adenosine
      monophosphate-activated protein kinase (AMPK). DESIGN: In vitro experimental
      study. SETTING: Academic medical center laboratory. ANIMAL(S): Immature Sprague
      Dawley female rats. INTERVENTION(S): Ovarian T-I cells were isolated, purified,
      and cultured in the absence (control) or presence of insulin (1 MUg/mL) with or
      without metformin or other activators/inhibitors of AMPK (AICAR, compound C).
      MAIN OUTCOME MEASURE(S): Proliferation assessed by determination of expression
      levels of proteins involved in cell cycle progression, cyclin D3, and cyclin
      dependent kinase 4 (CDK4) with Western blot analysis, and determination of DNA
      synthesis with bromodeoxyuridine (BrdU) incorporation assay; activation of AMPK,
      Erk1/2, and S6K1 determined by Western blot analysis with the use of antibodies
      specific for the phosphorylated (activated) forms. RESULT(S): Metformin inhibited
      insulin-induced ovarian T-I cell proliferation and the up-regulation of the cell
      cycle regulatory proteins, cyclin D3 and CDK4. Metformin independently activated
      AMPK in a dose-dependent manner. Treatment with metformin inhibited insulin
      induced activation of Erk1/2 and S6K1. This effect was reversed with the addition
      of compound C, a known AMPK inhibitor. CONCLUSION(S): Metformin directly inhibits
      proliferation of ovarian T-I cells via an AMPK-dependent mechanism. These
      findings further validate the potential benefits of metformin in the treatment of
      conditions associated with hyperinsulinemia and excessive growth of ovarian T-I
      cells (such as polycystic ovary syndrome).

PMID- 22608321
TI  - Genomics and world health: a decade on.

PMID- 22608322
TI  - Extending the reach of BRAF-targeted cancer therapy.

PMID- 22608323
TI  - A first for mental health in Canada.

PMID- 22608325
TI  - Drug regulation in India--the time is ripe for change.

PMID- 22608326
TI  - Lisa Bero: taking the path of most resistance.

PMID- 22608327
TI  - Tackling NCDs: a different approach is needed.

PMID- 22608328
TI  - Tackling NCDs: a different approach is needed.

PMID- 22608330
TI  - Non-specific low back pain.

PMID- 22608332
TI  - Intravenous salbutamol in ARDS and increased mortality.

PMID- 22608334
TI  - BiDil: alive and kicking.

PMID- 22608336
TI  - Educating for the future: another important benefit of data sharing.

PMID- 22608337
TI  - Urgent need for WHO's reform to prioritise core functions.

PMID- 22608338
TI  - Dabrafenib in patients with melanoma, untreated brain metastases, and other solid
      tumours: a phase 1 dose-escalation trial.
AB  - BACKGROUND: Dabrafenib is an inhibitor of BRAF kinase that is selective for
      mutant BRAF. We aimed to assess its safety and tolerability and to establish a
      recommended phase 2 dose in patients with incurable solid tumours, especially
      those with melanoma and untreated, asymptomatic brain metastases. METHODS: We
      undertook a phase 1 trial between May 27, 2009, and March 20, 2012, at eight
      study centres in Australia and the USA. Eligible patients had incurable solid
      tumours, were 18 years or older, and had adequate organ function. BRAF mutations
      were mandatory for inclusion later in the study because of an absence of activity
      in patients with wild-type BRAF. We used an accelerated dose titration method,
      with the first dose cohort receiving 12 mg dabrafenib daily in a 21-day cycle.
      Once doses had been established, we expanded the cohorts to include up to 20
      patients. On the basis of initial data, we chose a recommended phase 2 dose.
      Efficacy at the recommended phase 2 dose was studied in patients with BRAF-mutant
      tumours, including those with non-Val600Glu mutations, in three cohorts:
      metastatic melanoma, melanoma with untreated brain metastases, and non-melanoma
      solid tumours. This study is registered with ClinicalTrials.gov, number
      NCT00880321. FINDINGS: We enrolled 184 patients, of whom 156 had metastatic
      melanoma. The most common treatment-related adverse events of grade 2 or worse
      were cutaneous squamous-cell carcinoma (20 patients, 11%), fatigue (14, 8%), and
      pyrexia (11, 6%). Dose reductions were necessary in 13 (7%) patients. No deaths
      or discontinuations resulted from adverse events, and 140 (76%) patients had no
      treatment-related adverse events worse than grade 2. Doses were increased to 300
      mg twice daily, with no maximum tolerated dose recorded. On the basis of safety,
      pharmacokinetic, and response data, we selected a recommended phase 2 dose of 150
      mg twice daily. At the recommended phase 2 dose in 36 patients with Val600 BRAF
      mutant melanoma, responses were reported in 25 (69%, 95% CI 51.9-83.7) and
      confirmed responses in 18 (50%, 32.9-67.1). 21 (78%, 57.7-91.4) of 27 patients
      with Val600Glu BRAF-mutant melanoma responded and 15 (56%, 35.3-74.5) had a
      confirmed response. In Val600 BRAF-mutant melanoma, responses were durable, with
      17 patients (47%) on treatment for more than 6 months. Responses were recorded in
      patients with non-Val600Glu BRAF mutations. In patients with melanoma and
      untreated brain metastases, nine of ten patients had reductions in size of brain
      lesions. In 28 patients with BRAF-mutant non-melanoma solid tumours, apparent
      antitumour activity was noted in a gastrointestinal stromal tumour, papillary
      thyroid cancers, non-small-cell lung cancer, ovarian cancer, and colorectal
      cancer. INTERPRETATION: Dabrafenib is safe in patients with solid tumours, and an
      active inhibitor of Val600-mutant BRAF with responses noted in patients with
      melanoma, brain metastases, and other solid tumours. FUNDING: GlaxoSmithKline.

PMID- 22608339
TI  - Scaling up interventions to achieve global tuberculosis control: progress and new
      developments.
AB  - Tuberculosis is still one of the most important causes of death worldwide. The
      2010 Lancet tuberculosis series provided a comprehensive overview of global
      control efforts and challenges. In this update we review recent progress. With
      improved control efforts, the world and most regions are on track to achieve the
      Millennium Development Goal of decreasing tuberculosis incidence by 2015, and the
      Stop TB Partnership target of halving 1990 mortality rates by 2015; the exception
      is Africa. Despite these advances, full scale-up of tuberculosis and HIV
      collaborative activities remains challenging and emerging drug-resistant
      tuberculosis is a major threat. Recognition of the effect that non-communicable
      diseases--such as smoking-related lung disease, diet-related diabetes mellitus,
      and alcohol and drug misuse--have on individual vulnerability, as well as the
      contribution of poor living conditions to community vulnerability, shows the need
      for multidisciplinary approaches. Several new diagnostic tests are being
      introduced in endemic countries and for the first time in 40 years a coordinated
      portfolio of promising new tuberculosis drugs exists. However, none of these
      advances offer easy solutions. Achievement of international tuberculosis control
      targets and maintenance of these gains needs optimum national health policies and
      services, with ongoing investment into new approaches and strategies. Despite
      growing funding in recent years, a serious shortfall persists. International and
      national financial uncertainty places gains at serious risk. Perseverance and
      renewed commitment are needed to achieve global control of tuberculosis, and
      ultimately, its elimination.

PMID- 22608340
TI  - A heart without hormones.

PMID- 22608341
TI  - The real McCoy?

PMID- 22608342
TI  - The saga of the Romanian health-care reform.

PMID- 22608343
TI  - Dysphagia due to isoniazid therapy for tuberculosis in a patient with Lewy body
      dementia.
AB  - Dementia with Lewy bodies (DLB) potentially causes dysphagia; however, the
      features and underlying mechanism causing dysphagia have still not been
      clarified. We are the first to report a case of dysphagia resulting from
      isoniazid therapy for tuberculosis in a DLB patient. A 74-year-old woman with DLB
      developed dysphagia during treatment for tuberculous pleurisy. Oral
      videoendoscopic and videofluorographic swallowing examinations showed
      oropharyngeal dysphagia. The increased administration of levodopa successfully
      ameliorated dysphagia. Therefore, dysphagia was ascribed to diminished levodopa
      efficacy due to interaction with isoniazid. Thus, DLB patients receiving anti
      tuberculous therapy should be closely examined for potential changes in
      swallowing and Parkinsonism.

PMID- 22608344
TI  - Intravenous thrombolysis in a stroke patient taking dabigatran.
AB  - We describe the use of intravenous thrombolysis with recombinant tissue
      plasminogen activator (IV-rtPA) in a patient with concomitant dabigatran use. A
      64-year-old man with a history of coronary artery disease, pacemaker placement,
      and atrial fibrillation developed acute right arm/face weakness and dysarthria.
      He was unable to list his home medications. His platelet count was 167 * 10(9)/L
      (normal 150-399 * 10(9)/L), and his activated partial thromboplastin time (aPTT)
      was 37.6 seconds (normal 24.0-33.0 seconds). His international normalized ratio
      (INR) was 1.1. He received IV-rtPA at 3 hours and 25 minutes after the onset of
      symptoms. After IV-rtPA was administered, it was discovered that the patient had
      been taking dabigatran for 2 months. After IV-rtPA, the patient developed severe
      superficial left arm ecchymoses but remained without cerebral complications. On
      poststroke day 1, his fibrinogen level was low at 63 mg % (normal 190-395 mg %),
      his aPTT was normal at 33, and his INR was elevated at 1.72 but decreased to 1.18
      on the following day. Repeat computed tomographic imaging of his brain confirmed
      a left middle cerebral artery ischemic cortical infarct. We report a case of an
      acute stroke patient taking dabigatran who received IV-rtPA. In the acute stroke
      setting, clinicians should be aware of the increasing use of dabigatran in
      patients with atrial fibrillation when considering IV-rtPA. Although aPTT does
      not provide a linear response to dabigatran therapy, the presence of a completely
      normal PTT may exclude therapeutic dabigatran anticoagulation.

PMID- 22608345
TI  - Bow hunter's syndrome after contralateral vertebral artery dissection.
AB  - Bow hunter's syndrome is characterized by transient vertebrobasilar insufficiency
      that is elicited by neck rotation. This syndrome is has various causes, such as
      osteophytes, tumors, fibrous bands, infection, and trauma. We report a unique
      case of bow hunter's syndrome. The patient visited our hospital because of left
      nuchal pain. A magnetic resonance imaging scan revealed left vertebral artery
      (VA) dissection, which was the cause of his nuchal pain. He began to feel
      faintness upon turning his neck to the left after left VA dissection. Digital
      subtraction angiography revealed that the right VA was fully patent in a neutral
      neck position, but focal stenosis appeared at the C2 vertebral level upon turning
      his head 60 degrees  to the left. This stenosis became complete occlusion at
      turning his head to the end of his range of motion. From these findings, a
      diagnosis of bow hunter's syndrome was made. Dissection of the contralateral
      (left) VA caused a failure in compensatory blood flow, resulting in bow hunter's
      syndrome. This represents the first report of bow hunter's syndrome occurring
      after onset of the contralateral VA dissection.

PMID- 22608347
TI  - Medical ultrasound image compression using contextual vector quantization.
AB  - With ever increasing use of medical ultrasound (US) images, a challenge exists to
      deal with storage and transmission of these images while still maintaining high
      diagnostic quality. In this article, a state-of-the-art context based method is
      proposed to overcome this challenge called contextual vector quantization (CVQ).
      In this method, a contextual region is defined as a region containing the most
      important information and must be encoded without considerable quality loss.
      Attempts are made to encode this region with high priority and high resolution
      (low compression ratio and high bit rate) CVQ algorithm; and the background,
      which has a lower priority, is separately encoded with a low resolution (high
      compression ratio and low bit rate) version of the CVQ algorithm. Finally both of
      the encoded contextual region and the encoded background region is merged
      together to reconstruct the output image. As a result, very good diagnostic image
      quality with lower image size and enhanced performance parameters including mean
      square error (MSE), pick signal to noise ratio (PSNR) and coefficient of
      correlation (CoC) are gained. The experimental results show that the proposed CVQ
      methodology is superior as compared to other existing methods (general methods
      such as JPEG and JPEG2K, and ROI based methods such as EBCOT and CSPIHT) in terms
      of measured performance parameters. This makes CVQ compression method a feasible
      technique to overcome storage and transmission limitations.

PMID- 22608346
TI  - Cerebral white matter hyperintensity in African Americans and European Americans
      with type 2 diabetes.
AB  - Previous studies involving inner city populations detected higher cerebral white
      matter hyperintensity (WMH) scores in African Americans (AAs) compared with
      European Americans (EAs). This finding might be attributable to the higher
      prevalence of cardiovascular disease (CVD) risk factors and poorer access to
      healthcare in AAs. Despite racial differences in CVD risk factor profiles, AAs
      have paradoxically lower levels of subclinical CVD. We hypothesized that AAs with
      diabetes and good access to healthcare would have comparable or lower levels of
      WMH as EAs. Racial differences in the distribution of WMH were analyzed in 46 AAs
      and 156 EAs with type 2 diabetes enrolled in the Diabetes Heart Study (DHS)-Mind,
      and replicated in a sample of 113 AAs and 61 EAs patients who had clinically
      indicated cerebral magnetic resonance imaging. Wilcoxon 2-sample tests and linear
      models were used to compare the distribution of WMH in AAs and EAs and to test
      for association between WMH and race. The unadjusted mean WMH score from the
      Diabetes Heart Study-Mind was 1.9 in AAs and 2.3 in EAs (P = .3244). Among those
      with clinically indicated magnetic resonance imaging, the mean WMH score was 2.9
      in AAs and 3.9 in EAs (P = .0503). Adjustment for age and sex produced no
      statistically significant differences in WMH score between AAs and EAs. These
      independent datasets reveal comparable WMH scores in AAs and EAs, suggesting that
      disparities in access to healthcare and environmental exposures likely underlie
      the previously reported excess burden of WMH in AAs. 

PMID- 22608348
TI  - Macrolide-resistant Bordetella pertussis infection in newborn girl, France.
AB  - A macrolide antimicrobial drug was administered to a newborn with cough. On day
      23 of hospitalization, macrolide-resistant Bordetella pertussis was isolated from
      nasopharyngeal aspirates. DNA sequencing and PCR-restriction fragment length
      polymorphism showed a 2047 A-to-G mutation in the 3 copies of the 23S rRNA gene.
      Monitoring for macrolide resistance is essential in infants <6 months of age.

PMID- 22608349
TI  - Effect of Calea serrata Less. n-hexane extract on acetylcholinesterase of larvae
      ticks and brain Wistar rats.
AB  - Acetylcholinesterase (AChE), an enzyme that hydrolyses acetylcholine (ACh) at
      cholinergic synapses, is a target for pesticides and its inhibition by
      organophosphates leads to paralysis and death of arthropods. It has been
      demonstrated that the n-hexane extract of Calea serrata had acaricidal activity
      against larvae of Rhipicephalus (Boophilus) microplus and Rhipicephalus
      sanguineus. The aim of the present study was to understand the mechanism of the
      acaricidal action of C. serrata n-hexane extract are specifically to investigate
      the in vitro anticholinesterase activity on larvae of R. microplus and in brain
      structures of male Wistar rats. The n-hexane extract significantly inhibited in
      vitro acetylcholinesterase activity in R. microplus larvae and rat brain
      structures. The results confirm that inhibition of acetylcholinesterase is a
      possible mechanism of action of hexane extract at C. serrata.

PMID- 22608350
TI  - Fusion of talonavicular and naviculocuneiform joints for the treatment of Muller
      Weiss disease.
AB  - Muller-Weiss disease is a rare spontaneous osteonecrosis of the tarsal and
      navicular bones in adults. From April 2008 to April 2011, we treated 7 patients
      with Muller-Weiss disease by surgical fusion of the talonavicular and
      naviculocuneiform joints with tricortical autologous iliac crest block fixated by
      screws and plate. Preoperative and postoperative clinical outcomes were evaluated
      with the American Orthopaedic Foot and Ankle Society ankle-hindfoot scale. The
      median follow-up time was 22 (range 3 to 38) months. All of the operated feet
      fused solidly. The median time for solid fusion was 13 (range 12 to 16) weeks.
      The median American Orthopaedic Foot and Ankle Society ankle-hindfoot score
      improved from 49 (range 15 to 66) points preoperatively to 82 (range 68 to 87)
      points at last follow-up. The results suggest that this type of fusion is an
      effective surgical treatment for Muller-Weiss disease.

PMID- 22608351
TI  - Idiopathic transient osteoporosis of the talus: a cause for unexplained foot and
      ankle pain.
AB  - A 53-year-old woman was investigated for several neoplastic, inflammatory, and
      infective conditions for her left foot, and ankle pain associated with swelling,
      which she developed unexpectedly without history of trauma or infection. Gross
      osteopenia in the talus raised the possibilities of several differential
      diagnoses, but a magnetic resonance imaging scan showed diffuse bone marrow edema
      in the talus. With negative infective and inflammatory markers, the condition was
      ultimately labeled as "transient osteoporosis." She was reassured and followed up
      regularly. At the end of 12 months, she was completely asymptomatic, and her
      radiograph and magnetic resonance images showed significant improvement, with a
      normal-appearing talus and ankle joint, and there was complete resolution of bone
      marrow edema. Although "transient osteoporosis" of the foot is an uncommon
      condition, clinicians should be aware of this. Unexplained foot pain, with
      osteopenic bone and diffuse bone marrow edema on magnetic resonance imaging scan,
      is a feature of this condition. However, the diagnosis is established once other
      causes are excluded. The condition is self-limiting, and watchful expectancy of a
      normal recovery is the mainstay of treatment.

PMID- 22608352
TI  - Ciliary beating is depressed in nasal cilia from chronic obstructive pulmonary
      disease subjects.
AB  - COPD is characterized by increased cough, mucus production, and airway
      inflammation. Beating epithelial cell cilia contribute to mucociliary clearance
      with ciliary beat frequency (CBF) an important measure of cilia function.
      However, whether CBF varies with COPD severity is unknown. AIMS: 1) to compare
      nasal cilia samples and their CBF from healthy non-smokers (Control), COPD and At
      Risk (cough and sputum production) subjects. 2) to determine the effect of
      pharmacologic agents that modulate mediators implicated in the pathogenesis of
      COPD on nasal CBF. Nasal brushings of ciliated cells were obtained from Control,
      At Risk and COPD subjects. Using high speed digital imaging, we measured baseline
      CBF ex vivo. Then, CBF was re-measured after 30 min perfusion with pharmacologic
      agents that modulate mediators implicated in COPD (salmeterol xinafoate,
      tiotropium bromide, licofelone, luteolin, YM976, Defensin HNP-1) and again after
      30 min washout. CBF was significantly depressed in moderate and severe COPD
      compared to At Risk and Control subjects. There was an evident and persistent
      rise in CBF with all agents tested in COPD cilia except that YM976 effects
      persisted only in severe COPD. Only YM976 and tiotropium caused a persistent
      increase in CBF in At Risk cilia. The reduction of nasal CBF in moderate and
      severe COPD implies that impaired ciliary function may impact mucociliary
      clearance in COPD, potentially contributing to retention of secretions and
      infection. Pharmacologic agents with different mechanisms of action can increase
      CBF of COPD cilia. Further investigation of the signalling pathways influencing
      CBF of COPD cilia is needed.

PMID- 22608353
TI  - Outcome of patients diagnosed with fibrinous pleuritis after medical
      thoracoscopy.
AB  - BACKGROUND: In patients with post- medical thoracoscopy histopathological
      diagnoses of fibrinous pleuritis, confusion can occur concerning subsequent
      procedures. This issue is particularly important in regions where mesothelioma is
      prevalent. We aimed to identify false negatives among patients where mesothelioma
      was common due to asbestos exposure whose histopathological diagnosis following
      thoracoscopy was fibrinous pleuritis. We also determined risk factors associated
      with patients that required additional advanced invasive procedures for
      diagnosis. METHODS: Overall, 287 patients who underwent thoracoscopy were
      included in the study. Patients diagnosed with fibrinous pleuritis as a result of
      thoracoscopy were followed for 2 years regarding this condition. More invasive
      procedures were performed on patients who showed no recuperation or developed
      pleural disease again during the follow-up period. RESULTS: Fibrinous pleuritis
      was observed in 101 (35.2%) patients. Follow-up of these patients revealed that
      the false negative rate was 18% for malignant pleural diseases. The
      thoracoscopist's opinion regarding the pleural space, computed tomography scan
      findings indicating malignancy, pain and female gender were determined to be risk
      factors for malignant pleural diseases. CONCLUSIONS: In regions where
      mesothelioma is prevalent and one of the above-stated risk factors is present,
      patients whose post-thoracoscopy histopathological diagnosis is fibrinous
      pleuritis should be treated with a more advanced invasive diagnosis procedure.

PMID- 22608354
TI  - Novel membrane extraction procedure for the purification of hepatitis B surface
      antigen from Pichia pastoris.
AB  - The recombinant hepatitis B surface antigen (HBsAg) vaccine provides excellent
      protection against hepatitis B virus (HBV). However, high costs of its production
      prevents many underdeveloped and developing nations from implementing HBsAg
      vaccination. This in turn increases the risk of contracting HBV related diseases.
      Majority of the commercial HBV vaccines are derived from purified HBsAg expressed
      in recombinant yeasts. Most of the cost in production of the vaccine is incurred
      during the downstream processing. The costs associated with HBsAg purification
      can be decreased by optimizing the pre-chromatography steps and by reducing the
      impurity burden on chromatography operations. Here in this work we present a
      novel strategy for the enriched extraction of recombinant HBsAg from Pichia
      pastoris membranes. We have also developed a simple, easy to operate process for
      the purification of HBsAg VLPs from the membranes of P. pastoris. This novel
      strategy, while utilizing a single column chromatographic step in the
      purification scheme results in the highest recovery of HBsAg VLPs reported in the
      literature. The yield of HBsAg at the end of purification was nearly 5% (85 MUg/g
      of induced wet cell biomass). The HBsAg purified from this process has shown the
      presence of VLPs. The immunization of these VLPs in BALB/c mice with alhydrogel
      adjuvant has shown good titers of neutralizing antibodies.

PMID- 22608355
TI  - Aortic valve cusp shearing and migration into the left main coronary artery
      during transcatheter aortic valve implantation.
AB  - In inoperable or high-risk patients with severe aortic stenosis, transcatheter
      aortic valve implantation (TAVI) provides an efficacious and safe alternative to
      surgical aortic valve replacement. In this case report, TAVI resulted in aortic
      valve cusp shearing and migration into the left main coronary artery, resulting
      in occlusion of coronary blood flow and cardiac arrest. The patient underwent
      immediate cardiopulmonary support and surgical intervention with a favourable
      outcome. With this case report, we illustrate the etiology and management of this
      complication, which can be recognized nonsurgically only if a high index of
      suspicion exists.

PMID- 22608356
TI  - Coronary artery occlusion as a complication of transcatheter aortic valve
      implantation.

PMID- 22608357
TI  - Acute effects of adaptive servo ventilation on hemodynamics, coronary flow, and
      flow reserve in a patient with idiopathic dilated cardiomyopathy.
AB  - Adaptive servo ventilation (ASV) is reported to be effective for the treatment of
      heart failure. We treated a patient with idiopathic dilated cardiomyopathy using
      ASV and assessed the effects on hemodynamics, coronary flow, and flow reserve
      before and after ASV therapy. This case suggests that ASV might decrease
      myocardial oxygen demand, which was represented by the decreased resting coronary
      flow velocity (the improvement of coronary flow velocity reserve) on ASV.

PMID- 22608358
TI  - Isolated nonspecific ST-segment and T-wave abnormalities in a cross-sectional
      United States population and Mortality (from NHANES III).
AB  - Most clinicians regard isolated, minor, or nonspecific ST-segment and T-wave (NS
      STT) abnormalities to be incidental, often transient, and benign findings in
      asymptomatic patients. We sought to evaluate whether isolated NS-STT
      abnormalities on routine electrocardiograms (ECGs) are associated with increased
      risk of cardiovascular mortality (CM) and all-cause mortality (AM) in a cross
      sectional United States population without known coronary artery disease. We
      included all adults 40 to 90 years of age without known coronary artery disease
      or risk equivalent based on history and laboratory values, enrolled in the NHANES
      III from 1988 to 1994, with electrocardiographic data available, and a total
      follow-up period of 59,781.75 patient-years. NS-STT abnormalities were defined by
      Minnesota Coding. Subjects were excluded if their mortality data were missing or
      if they had major electrocardiographic abnormalities, heart rate >120 beats/min,
      nonsinus rhythm, cardiac infarction/injury score >= 20 on ECG, left ventricular
      hypertrophy by Minnesota Codes 3.1 and 3.3, or patient-reported history coronary
      artery disease, congestive heart failure, stroke, diabetes, or peripheral
      arterial disease. The remaining 4,426 subjects were stratified by presence or
      absence of NS-STT abnormalities. Mortality was judged based on International
      Classification of Diseases, Tenth Revision coding linked to the National Death
      Index. Cox proportional hazard ratio was used for multivariate analysis, showing
      that CM (hazards ratio 1.71, 95% confidence interval 1.04 to 2.83, p = 0.04) and
      AM (hazards ratio 1.37, 95% confidence interval 1.03 to 1.81, p = 0.02) were
      significantly higher in the isolated NS-STT abnormalities group. In conclusion,
      isolated NS-STT abnormalities on ECG were associated with a higher incidence of
      CM and AM in this large nationally representative cross-sectional cohort without
      known coronary artery disease or coronary artery disease risk equivalents.

PMID- 22608359
TI  - Effect of coenzyme Q10 supplementation on statin-induced myalgias.
AB  - Coenzyme Q10 (CoQ10) deficiency has been proposed to be causal in 3-hydroxy-3
      methyl-glutaryl coenzyme A reductase inhibitor (statin)-induced myopathies.
      However, the clinical benefit of supplementation is unproved. The purpose of the
      present study was to assess the effect of CoQ10 supplementation on myalgias
      presumed to be caused by statins. Patients currently receiving a statin who
      developed new-onset myalgias in >= 2 extremities within 60 days of initiation or
      a dosage increase were eligible. Patients continued statin therapy and were
      randomized using a matched design to either CoQ10 60 mg twice daily or matching
      placebo. Double-blind treatment continued for 3 months, and patients completed a
      10-cm visual analog scale (VAS) and the Short-Form McGill Pain Questionnaire at
      baseline and at each monthly visit. The primary end point was the comparison of
      the VAS score at 1 month. A total of 76 patients were enrolled (40 in the CoQ10
      arm and 36 in the placebo arm). The mean VAS score was 6 cm at baseline in both
      groups. At 1 month, no difference was seen in the mean VAS score between the 2
      groups (3.9 cm in the CoQ10 group and 4 cm in the placebo group; p = 0.97).
      However, 5 patients in the CoQ10 group and 3 in the placebo group discontinued
      therapy during the first month because of myalgias. The baseline median score on
      the Sensory Pain Rating Index subscale was 10 in the CoQ10 group and 11.5 in the
      placebo group. At 1 month, these scores had decreased to 6.5 and 7.5,
      respectively, with no statistically significant difference (p = 0.34). In
      conclusion, CoQ10 did not produce a greater response than placebo in the
      treatment of presumed statin-induced myalgias.

PMID- 22608360
TI  - Relation of neutrophil/lymphocyte ratio to coronary flow to in-hospital major
      adverse cardiac events in patients with ST-elevated myocardial infarction
      undergoing primary coronary intervention.
AB  - With the growing understanding of the role of inflammation in patients with
      atherosclerotic disease, studies have focused on high-sensitivity C-reactive
      protein (hs-CRP) and other inflammatory markers in their association with
      outcomes in ST-segment elevation myocardial infarction. The goal of this study
      was to investigate the association of the neutrophil/lymphocyte (N/L) ratio and
      in-hospital major adverse cardiac events (MACEs) in patients with ST-segment
      elevation myocardial infarction undergoing primary percutaneous coronary
      intervention (PCI). The association of hs-CRP and N/L ratio on admission with
      Thrombolysis In Myocardial Infarction (TIMI) flow grade after PCI was assessed in
      418 consecutive primary patients with PCI. The N/L ratio was significantly higher
      in the no-reflow group (TIMI grade 0/1/2 flow, n = 158) compared to that of the
      normal-flow group (TIMI grade 3 flow, n = 260, 4.6 +/- 1.7 vs 3.1 +/- 1.9, p
      <0.001). In-hospital MACEs were significantly higher in patients with no reflow
      (23% vs 7%, p <0.001). There was a significant and positive correlation between
      hs-CRP and N/L ratio (r = 0.657, p <0.001). In receiver operating characteristic
      analysis, N/L ratio >3.3 predicted no reflow with 74% sensitivity and 83%
      specificity. In a multivariate regression model, N/L ratio remained an
      independent correlate of no reflow (odds ratio [OR] 1.54, 95% confidence interval
      [CI] 1.34 to 1.76, p <0.001) and in-hospital MACEs (OR 1.14, 95% CI 0.98 to 1.32,
      p = 0.043). The N/L ratio, an inexpensive and easily measurable laboratory
      variable, is independently associated with the development of no reflow and in
      hospital MACEs in patients with ST-segment elevation myocardial infarction
      undergoing primary PCI.

PMID- 22608361
TI  - Radiation fibrosis--current clinical and therapeutic perspectives.
AB  - Cancer survivors previously treated with curative radiotherapy are at risk of
      developing long-term toxicities due to radiation-induced normal tissue injury.
      Radiation fibrosis is an important component of the spectrum of radiation injury
      and at the present time treatment for this condition is limited. Data from both
      studies of clinical intervention and from preclinical models support the idea
      that fibrosis is a dynamic process and may in part be reversible. Clinical
      therapeutic interventions for radiation fibrosis have included empirical
      treatments, such as antioxidant therapies using superoxide dismutase, or vitamin
      E and pentoxifylline, and although evidence for therapeutic efficacy exists,
      further randomised studies are required. Potential therapeutic strategies that
      have shown promise in preclinical models include targeting pro-fibrotic cytokines
      such as: (1) transforming growth factor beta 1, (2) platelet-derived growth
      factor and its receptor tyrosine kinase and (3) connective tissue growth factor
      and the Rho/ROCK intracellular signalling pathway. Progress in the understanding
      of stem cell biology and the involvement of stem cells in radiation injury has
      led to the investigation of their role as a therapeutic strategy for ameliorating
      this disease process by promoting organ regeneration and repair. In this review
      we discuss the clinical and pathological features of radiation fibrosis and
      present the available clinical data and laboratory data relevant to these
      approaches to therapeutic intervention.

PMID- 22608362
TI  - Cancer care Ontario guideline recommendations for hormone receptor testing in
      breast cancer.
AB  - Hormone receptor testing (oestrogen and progesterone) in breast cancer at the
      time of primary diagnosis is used to guide treatment decisions. Accurate and
      standardised testing methods are critical to ensure the proper classification of
      the patient's hormone receptor status. Recommendations were developed to improve
      the quality and accuracy of hormone receptor testing based on a systematic review
      conducted jointly by the American Society of Clinical Oncology/College of
      American Pathologists and Cancer Care Ontario's Program in Evidence-Based Care.
      Evidence-based recommendations were formulated to set standards for optimising
      immunohistochemistry in assessing hormone receptor status, as well as assuring
      quality and proficiency between and within laboratories. A formal external review
      was conducted to validate the relevance of these recommendations. It is
      anticipated that widespread adoption of these guidelines will further improve the
      accuracy of hormone receptor testing in Canada.

PMID- 22608363
TI  - Human parechovirus infections, Lyon, France, 2008-10: evidence for severe cases.
AB  - BACKGROUND: Although data documenting the frequency and severity of human
      parechovirus type 3 (HPeV-3) infection in infants have been published in Canada,
      the USA, the UK and the Netherlands, no data from France are available.
      OBJECTIVES: To determine the detection frequency of HPeV in cerebrospinal fluid
      (CSF) samples collected from children aged <5 years hospitalized between 2008 and
      2010 in the University Hospital of Lyon and to describe the clinical, virological
      and biological characteristics associated with HPeV infection. STUDY DESIGN: A
      total of 1128 CSF samples were retrospectively tested using the Parechovirus
      RgeneTM real-time RT-PCR assay. Positive samples were typed by sequencing using
      the CDC method. Retrospective analysis of the medical charts was performed.
      RESULTS: Over a 3-year period, 33/1128 (2.9%) CSF samples were found to be HPeV
      positive. In 2010, 9.3% of the children aged <3 months (32% in June) were
      detected HPeV-positive. The median age at diagnosis was 26 days (8-131 days).
      Most patients (86%) presented with fever or a sepsis-like syndrome. Three
      patients (2 with septic shock syndrome, 1 with severe respiratory distress)
      required hospitalization in an intensive care unit. An HPeV-3 acute infection was
      identified in an 11-day-old girl who died from sudden infant death syndrome. Of
      29 patients genotyped, 28 were infected with HPeV-3 and one with HPeV-4.
      CONCLUSIONS: HPeV is a significant cause of sepsis and severe sepsis in children
      <3 months. Routine screening for HPeV in CSF and blood should thus be performed
      more extensively and could improve clinical management.

PMID- 22608364
TI  - Genotype impact on long-term virological outcome of chronic hepatitis B virus
      infection.
AB  - BACKGROUND: The importance of hepatitis B virus (HBV) genotype on the clinical
      course of chronic HBV infection is not yet clarified. OBJECTIVES: To investigate
      genotype impact on long-term virological outcome of chronic HBV infection. STUDY
      DESIGN: HBsAg, HBeAg, ALT and HBV DNA levels were determined after a median of
      9.2 years of follow-up of 124 adults with chronic HBV infection, of whom 33 were
      HBeAg-positive at inclusion. RESULTS: HBV DNA levels decreased significantly in
      patients carrying genotype A (n=28), B (n=21) or D (n=63), but not in those with
      genotype C infection (n=12). Loss of HBeAg was seen in 44% (4/9) of patients with
      genotype C, as compared with 92% (22/24) with non-C genotypes. Loss of HBsAg was
      seen in 36% (10/28) patients with genotype A, 5% (1/21) with B, 0% (0/12) with C,
      and 11% (7/63) with genotype D. CONCLUSIONS: HBV DNA levels decreased over time
      in patients infected with genotypes A, B or D. However, highly active genotype C
      or D infection often remained highly active, implying a risk for progressive
      liver damage.

PMID- 22608365
TI  - Adenovirus infections in Bordeaux University Hospital 2008-2010: clinical and
      virological features.
AB  - BACKGROUND: Transversal epidemiological data on adenovirus infections in a
      hospital setting, including both immuno-competent and transplanted patients, are
      limited and rarely contain the application of molecular virology. OBJECTIVES: To
      describe the clinical characteristics and molecular epidemiology of adenovirus
      infections in Bordeaux University Hospital from 2008 to 2010 (clinical data,
      viral load and adenovirus species distribution). STUDY DESIGN: Adenovirus DNA
      quantification (qPCR) and typing (sequencing of hexon and protein VI genes and
      protein VI polymerase chain reaction (PCR) product analysis) were applied
      retrospectively to 215 clinical samples from 105 adenovirus-infected patients
      (2008-2010, Bordeaux University Hospital). Clinical data were recovered and
      analysed for 73 children and 25 adults. RESULTS: Viral loads were measured in
      stools, upper and lower respiratory fluids, blood, urine and digestive tract
      biopsies; the highest values were observed in stools and respiratory samples.
      Stool viral loads were comparable whatever the immune status. Adenovirus was
      typed in 57 patients: species Human adenovirus (HAdV) C dominated (n=36),
      followed by B (n=15), F (n=5) and D (n=1). We could demonstrate no association
      between HAdV species and load or clinical severity (observed in most patients).
      In the immuno-compromised, in contrast to immuno-competent patients, adenovirus
      infections presented no seasonal variation. Co-infections were frequent: mostly
      bacterial in immuno-competent children (33%) and viral in immuno-compromised
      people (34%). CONCLUSIONS: The species HAdV C dominates the local ecology, in
      both respiratory and digestive tract infections, independently of the patient's
      immune status. Adenovirus infections, often associated with co-infection of
      bacterial or viral agents, frequently lead to severe clinical consequences in
      hospital patients.

PMID- 22608366
TI  - Roles of promoter and 3' untranslated motifs in expression of the human C5a
      receptor.
AB  - The C5a receptor (C5aR) is a 7 transmembrane G-protein coupled receptor (GPCR)
      that mediates the powerful pro-inflammatory effect of the complement activation
      product C5a. Excess C5a generated under pathological conditions has been
      implicated in a variety of conditions including sepsis, asthma and rheumatoid
      arthritis, but very little is known about the regulation of expression of the
      C5aR. The 5' promoter region and 3' untranslated region (UTR) of the C5aR mRNA
      were cloned, generating enhanced green fluorescent protein (EGFP)-reporter
      plasmids, which were transfected into the monocytic cell line U937. Most of the
      cloned 2kb 5' region was dispensable for the expression of the reporter
      constructs and the majority of regulatory sequences are in the first 200 bp.
      Three motifs, a NFkappaB, a CCAAT and a NFAT site, were identified to be of
      importance by site directed mutagenesis for basal expression. Analysis of the
      3'UTR of the C5aR mRNA showed that it contained two AU-rich elements (AREs),
      however site directed mutagenesis showed that these had no effect on basal
      expression. While the phorbol ester PMA and dibutyryl cAMP increased C5aR protein
      expression, these agents had no effect on the regulation of expression via the
      promoter or the 3'UTR. This is the first study to investigate the role of both
      the promoter and 3'UTR in regulating C5aR expression and our results show that
      regulation of the human C5aR is similar but not identical to that of the mouse
      C5aR.

PMID- 22608367
TI  - [Recommendations for breast cancer screening with mammography in the medium risk
      population: update of PAPPS 2012].

PMID- 22608368
TI  - [Short physical performance battery reference values for patients 70 years-old
      and over in primary health care].
AB  - OBJECTIVE: To provide new reference values for the Short Physical Performance
      Battery (SPPB) for patients 70 years-old and over in primary health care (PHC),
      and analyse their relationship with demographic data, physical function, health
      and clinical status. DESIGN: Baseline interviews and observations of a
      longitudinal study on physical function and adverse health results. SETTING: Five
      Primary Care Centres in the provinces of Alicante and Valencia. PARTICIPANTS: A
      total of 593 persons 70 years-old and over. MAIN MEASUREMENTS: The SPPB was
      applied using direct observation, and the rest of the variables by interview.
      Reference values were calculated according to sex and three age groups (70-75, 76
      80, > 80 years), and the validity of the Battery was analysed using association
      statistics with the demographic, clinical, and function data. RESULTS: The
      reference values showed a poor performance in women, and a gradually poorer
      performance through the three age groups. The SPPB was significantly associated
      (P < 0.01) with age, sex, number of drugs taken, morbidity, body mass index,
      dependency in basic activities of daily living (BADL), instrumental activities of
      daily living (IADL) for health reasons, the 10-item Physical Functioning Scale
      (PF-10), depression and health perception. CONCLUSIONS: The reference values of
      the complete SPPB by age and sex are provided, based category scores in Primary
      Care patients 70 years-old and over. The Battery results can give a rapid and
      valid assessment of the functional state of elderly patient in Primary Care.

PMID- 22608369
TI  - [Evolution of burnout and associated factors in primary care physicians].
AB  - PURPOSE: To analyse the course of burnout and develop an explanatory model.
      DESIGN: Prospective cohort dynamics. SITE: All primary health care centres in
      Burgos. SUBJECTS: All physicians except medical emergencies, paediatrics and
      residents. MAIN MEASUREMENTS: Anonymous self-report questionnaire: Maslach
      Burnout Inventory (MBI) and related variables. An analysis was performed using
      the Student-t, X(2) test and logistic regression. RESULTS: The response rate was
      47.76% in 2007, which was lower than that of 2005. There were significant
      differences between 2005 and 2007, for increases in the percentage of physicians
      who smoked, postgraduate training, residency, and those who believe that
      coordination with nursing and specialist care and institutional communication is
      appropriate. There was an increase in the prevalence of burnout by almost one
      point compared with 2005, a decrease in maximum burnout and emotional exhaustion
      (EC), and an increase in depersonalisation (DP) and personal accomplishment (RP).
      The incidence density of burnout was 1/113. 5 primary care physicians per year.
      The existence of burnout is associated with the use of chronic medication and
      inadequate coordination between nursing and EC, and also with the high workload.
      CONCLUSIONS: The increase in the prevalence found is consistent with the idea of
      burnout as a dynamic development and the theoretical model described. Stable and
      quality employment is one way to indirectly mitigate (by encouraging internal
      communication) professional burnout. In the multivariate analysis, the most
      critical variable in the onset of burnout is the inadequate coordination with
      nursing.

PMID- 22608370
TI  - [Immigration and healthy lifestyles in Spain].

PMID- 22608371
TI  - Obesity and severe obesity forecasts through 2030.
AB  - BACKGROUND: Previous efforts to forecast future trends in obesity applied linear
      forecasts assuming that the rise in obesity would continue unabated. However,
      evidence suggests that obesity prevalence may be leveling off. PURPOSE: This
      study presents estimates of adult obesity and severe obesity prevalence through
      2030 based on nonlinear regression models. The forecasted results are then used
      to simulate the savings that could be achieved through modestly successful
      obesity prevention efforts. METHODS: The study was conducted in 2009-2010 and
      used data from the 1990 through 2008 Behavioral Risk Factor Surveillance System
      (BRFSS). The analysis sample included nonpregnant adults aged >= 18 years. The
      individual-level BRFSS variables were supplemented with state-level variables
      from the U.S. Bureau of Labor Statistics, the American Chamber of Commerce
      Research Association, and the Census of Retail Trade. Future obesity and severe
      obesity prevalence were estimated through regression modeling by projecting
      trends in explanatory variables expected to influence obesity prevalence.
      RESULTS: Linear time trend forecasts suggest that by 2030, 51% of the population
      will be obese. The model estimates a much lower obesity prevalence of 42% and
      severe obesity prevalence of 11%. If obesity were to remain at 2010 levels, the
      combined savings in medical expenditures over the next 2 decades would be $549.5
      billion. CONCLUSIONS: The study estimates a 33% increase in obesity prevalence
      and a 130% increase in severe obesity prevalence over the next 2 decades. If
      these forecasts prove accurate, this will further hinder efforts for healthcare
      cost containment.

PMID- 22608372
TI  - Commuting distance, cardiorespiratory fitness, and metabolic risk.
AB  - BACKGROUND: Limited evidence exists on the metabolic and cardiovascular risk
      correlates of commuting by vehicle, a habitual form of sedentary behavior.
      PURPOSE: To examine the association between commuting distance, physical
      activity, cardiorespiratory fitness (CRF), and metabolic risk indicators.
      METHODS: This cross-sectional study included 4297 adults who had a comprehensive
      medical examination between 2000 and 2007 and geocoded home and work addresses in
      12 Texas metropolitan counties. Commuting distance was measured along the road
      network. Outcome variables included weekly MET-minutes of self-reported physical
      activity, CRF, BMI, waist circumference, triglycerides, plasma glucose, high
      density lipoprotein cholesterol, systolic and diastolic blood pressure, and
      continuously measured metabolic syndrome. Outcomes were also dichotomized using
      established cut-points. Linear and logistic regression models were adjusted for
      sociodemographic characteristics, smoking, alcohol intake, family history of
      diabetes, and history of high cholesterol, as well as BMI and weekly MET-minutes
      of physical activity and CRF (for BMI and metabolic risk models). Analyses were
      conducted in 2011. RESULTS: Commuting distance was negatively associated with
      physical activity and CRF and positively associated with BMI, waist
      circumference, systolic and diastolic blood pressure, and continuous metabolic
      score in fully adjusted linear regression models. Logistic regression analyses
      yielded similar associations; however, of the models with metabolic risk
      indicators as outcomes, only the associations with elevated blood pressure
      remained significant after adjustment for physical activity and CRF. CONCLUSIONS:
      Commuting distance was adversely associated with physical activity, CRF,
      adiposity, and indicators of metabolic risk.

PMID- 22608373
TI  - Fast-food environments and family fast-food intake in nonmetropolitan areas.
AB  - BACKGROUND: Little is known about the influence of in-town fast-food availability
      on family-level fast-food intake in nonmetropolitan areas. PURPOSE: The purpose
      of the current study was to determine whether the presence of chain fast-food
      outlets was associated with fast-food intake among adolescents and parents, and
      to assess whether this relationship was moderated by family access to motor
      vehicles. METHODS: Telephone surveys were conducted with 1547 adolescent-parent
      dyads in 32 New Hampshire and Vermont communities between 2007 and 2008. Fast
      food intake in the past week was measured through self-report. In-town fast-food
      outlets were located and enumerated using an onsite audit. Family motor vehicle
      access was categorized based on the number of vehicles per licensed drivers in
      the household. Poisson regression was used to determine unadjusted and adjusted
      risk ratios (RRs). Analyses were conducted in 2011. RESULTS: About half (52.1%)
      of adolescents and 34.7% of parents consumed fast food at least once in the past
      week. Adolescents and parents who lived in towns with five or more fast-food
      outlets were about 30% more likely to eat fast food compared to those in towns
      with no fast-food outlets, even after adjusting for individual, family, and town
      characteristics (RR=1.29, 95% CI= 1.10, 1.51; RR=1.32, 95% CI=1.07, 1.62,
      respectively). Interaction models demonstrated that the influence of in-town fast
      food outlets on fast-food intake was strongest among families with low motor
      vehicle access. CONCLUSIONS: In nonmetropolitan areas, household transportation
      should be considered as an important moderator of the relationship between in
      town fast-food outlets and family intake.

PMID- 22608374
TI  - Medicaid coverage and utilization of covered tobacco-cessation treatments: the
      Arkansas experience.
AB  - BACKGROUND: Although most Medicaid programs have some coverage for tobacco
      cessation treatments, little is known about how well the covered treatments are
      utilized among Medicaid enrollees. PURPOSE: To examine the impact of Arkansas
      Medicaid coverage of tobacco-cessation treatment on utilization of FDA-approved
      tobacco-cessation pharmacotherapies and counseling services by Medicaid
      enrollees. METHODS: This study used Arkansas Medicaid administrative claims data
      from October 1, 2003, to June 30, 2008. Trend changes in the following monthly
      measures were examined: (1) total number of pharmacy claims for each covered
      pharmacotherapy; (2) total number of medical claims for counseling services; and
      (3) total number of unique enrollees who received each type of covered tobacco
      cessation treatment. Average unit of defined daily dose and days with treatment
      stratified by tobacco-cessation products within 180 days after the first tobacco
      cessation treatment were examined for intensity of treatment. Data collection was
      finished in 2009 and analysis was completed in 2011. RESULTS: By June 30, 2008, a
      total of 12,673 enrollees received some tobacco-cessation treatments, and 77% of
      them received pharmacotherapies only. Implementation of the coverage expansion
      generated an initial increase in utilization of tobacco-cessation medications but
      quickly declined after 3 months. Utilization increased again when varenicline was
      added, but also decreased sharply after 6 months. Patterns of monthly claims for
      counseling services appeared to be inconsistent with the policy change.
      CONCLUSIONS: Medicaid coverage alone may have limited sustained effect on
      increasing utilization of the covered tobacco-cessation treatments among Medicaid
      enrollees.

PMID- 22608375
TI  - Healthcare costs around the time of smoking cessation.
AB  - BACKGROUND: The Affordable Care Act mandates that new insurance plans cover
      smoking-cessation therapy without cost-sharing. Previous cost difference
      estimates, which show a spike around the time of cessation, suggest premiums
      might rise as a result of covering these services. PURPOSE: The goal of the study
      was to test (1) whether individuals in an RCT of pharmacotherapy and counseling
      for smoking cessation differed in their healthcare costs around the cessation
      period, and (2) whether the healthcare costs of those in the trial who
      successfully quit were different from a matched sample of smokers in the
      community. METHODS: Generalized linear regression models were used to analyze
      healthcare cost data on individuals enrolled in a comparative effectiveness trial
      of cessation therapies between October 2005 and May 2007 (1346 total
      participants; 1338 with requisite data for further analysis). Cost differences
      for the period preceding and subsequent to the cessation attempt were assessed by
      trial participants' 12-month sustained quit status. Healthcare cost differences
      between sustained quitters and a sample of community-dwelling smokers, matched to
      these quitters on the basis of health services use around the time trial
      participant enrolled and by demographics, were also examined. Data were analyzed
      in 2011. RESULTS: All three groups had a spike in cost associated with the index
      clinic visit. Regression results revealed little difference in healthcare costs
      by quit status for trial participants until the sixth quarter post-quit. By that
      quarter, continuous sustained quitters cost $541 (p<0.001) less than continuing
      smokers. Continuous sustained quitters cost less than their matched community-
      dwelling smokers in almost every quarter observed. The cost difference ranged
      from $270 (p=0.01) during the quarter of quit, to $490 (p<0.01) in the 6th
      quarter after quitting. CONCLUSIONS: The inclusion of smoking-cessation therapy
      does not appear to raise short-term healthcare costs. By the sixth quarter post
      quit, sustained quitters were less costly than trial participants who continued
      smoking.

PMID- 22608376
TI  - Vaccine policy and Arkansas childhood immunization exemptions: a multi-year
      review.
AB  - BACKGROUND: An increase in total vaccine exemptions (medical, philosophic, and
      religious) occurred in Arkansas after a 2003 legislation added a philosophic
      category and used a new process for vaccine exemptions. By legislative
      requirement, the Arkansas Department of Health monitored exemptions through the
      2009-2010 school year. PURPOSE: The goal of the study was to determine the
      prevalence of vaccine exemption in 2003-2010 compared to the number of requests
      prior to the legislation enacted in 2003. METHODS: Exemptions were calculated by
      school-age category using raw numbers of exemptions, total estimates of the
      population by age level, enrollment numbers for students in public and private
      schools, and in enrolled college students born after 1957. Exemptions also were
      analyzed by school district, grade level, type of exemption, and particular
      vaccine exemption requested. RESULTS: Overall exemptions continued to rise each
      year, with an average increase of 23.1% annually. Medical exemptions declined
      from an average of 21.3% of all exemptions before to an average of 4.8%
      thereafter. The greatest increase in number of exemptions was observed among
      college students. The highest total rate of exemptions per precollegiate student
      population was <1.3%. When exemption requests were categorized, most (79%) were
      for exemptions from "all vaccines." The most common single exempted vaccine was
      MMR (measles, mumps, rubella). CONCLUSIONS: Since philosophic exemptions were
      codified in 2003 in Arkansas, the number and rate of vaccine exemptions continue
      to progressively increase. However, vaccine-preventable disease clusters have not
      yet been linked to or identified in any population with a high rate of vaccine
      exemptions.

PMID- 22608377
TI  - Mental illness and use of screening mammography among Medicaid beneficiaries.
AB  - BACKGROUND: Disparities in receipt of preventive services by people with mental
      illness have been documented previously. However, whether these disparities
      extend to screening mammography among individuals experiencing comparable
      barriers to accessing care has not been examined fully. PURPOSE: To determine
      whether disparities exist in receipt of screening mammography between women with
      and without mental illness enrolled in Medicaid, a program with documented
      potential to reduce healthcare disparities. METHODS: Receipt of screening
      mammography was examined among women aged 50-64 years enrolled in Ohio's Medicaid
      program during the years 2002-2008 (n=130,088). Receipt of annual screening
      mammography was examined among those with at least one screening mammography
      during the study period. Mental illness was identified through diagnostic,
      service, and pharmacotherapy codes (n=61,661). RESULTS: Compared to women without
      mental illness, more women with mental illness received at least one screening
      mammography during the study period (31.7% vs 38.1%, p<0.001). However, after
      adjusting for potential confounders, including the presence of comorbid
      conditions and length of enrollment in Medicaid, women with mental illness were
      32% less likely to undergo at least one screening mammography (AOR=0.68, 95%
      CI=0.66, 0.70). Among those who received at least one screening mammography,
      fewer women with mental illness received screening mammography on an annual basis
      (5.9% vs 12.7%, p<0.001; AOR=0.53, 95% CI=0.49, 0.56). For all beneficiaries,
      each year of enrollment in Medicaid increased the likelihood of screening
      mammography use by at least 50%. CONCLUSIONS: Medicaid beneficiaries with mental
      illness constitute a particularly vulnerable population for suboptimal breast
      cancer screening.

PMID- 22608378
TI  - Taking up cycling after residential relocation: built environment factors.
AB  - BACKGROUND: To successfully stimulate cycling, it is necessary to understand the
      factors that facilitate or inhibit cycling. Little is known about how changes in
      the neighborhood environment are related to changes in cycling behavior. PURPOSE:
      This study aimed to identify environmental determinants of the uptake of cycling
      after relocation. METHODS: The RESIDential Environment Project (RESIDE) is a
      longitudinal natural experiment of people moving into new housing developments in
      Perth (Western Australia). Self-reported usual transport and recreational cycling
      behavior, as well as self-reported and objective built environmental factors were
      measured before and after residential relocation. Participants who did not
      usually cycle at baseline in 2003-2004 were included in the study. Logistic
      regression models were used to relate changes in built environmental determinants
      to the probability of taking up cycling after relocation (2005-2006). Analyses
      were carried out in 2010-2011. RESULTS: At baseline, 90% (n=1289) of the
      participants did not cycle for transport and 86% (n=1232) did not cycle for
      recreation. After relocation, 5% of the noncyclists took up transport-related
      cycling, and 7% took up recreational cycling. After full adjustment, the uptake
      of transport-related cycling was determined by an increase in objective
      residential density (OR=1.54, 95% CI=1.04, 2.26) and self-reported better access
      to parks (OR=2.60, 95% CI=1.58, 4.27) and other recreation destinations (OR=1.57,
      95% CI=1.12, 2.22). Commencing recreational cycling mostly was determined by an
      increase in objective street connectivity (OR=1.20, 95% CI=1.06, 1.35).
      CONCLUSIONS: Changes in the built environment may support the uptake of cycling
      among formerly noncycling adults.

PMID- 22608379
TI  - Park improvements and park activity: a natural experiment.
AB  - BACKGROUND: Parks are an important setting for leisure-time physical activity.
      Understanding how to attract residents to parks and encourage park users to be
      physically active is an important public health initiative. Natural experiments
      are a research priority for investigating whether changes to the physical
      environment affect physical activity; however, natural experiments involving
      parks have rarely been conducted. PURPOSE: This natural experiment examined
      whether improvements to a park in Victoria, Australia, increased its use and park
      based physical activity of users. METHODS: Observational data were collected on
      park use and park-based activity among park users at the intervention park and a
      control park at three time points; baseline (T1, August 2009); post-improvement
      (T2, March 2010); and 12 months after baseline (T3, August 2010). At each time
      point, observations were undertaken during three 1.5-hour periods each day on 9
      days. Analyses were conducted in 2011. RESULTS: In the intervention park, there
      were significant increases from pre- to post-improvement in the number of park
      users (T1=235, T3=985) and the number of people observed walking (T1=155, T3=369)
      and being vigorously active (T1=38, T3=257). At the control park, counts of usage
      decreased over the same period and no differences in walking or vigorous activity
      were observed. CONCLUSIONS: Improving the features of a local neighborhood park
      may lead to increased usage and physical activity.

PMID- 22608380
TI  - Step test performance and risk of stress fractures among female army trainees.
AB  - BACKGROUND: Stress fractures and other musculoskeletal injuries are major sources
      of morbidity among female military trainees. Several risk factors have been
      postulated, particularly pre-existing fitness, usually assessed with post-entry
      run time for >= 1.0 mile. PURPOSE: Physical fitness is not formally evaluated
      prior to Army entry. If a valid and simple test that identified women at
      increased risk of stress fracture were available and could be applied prior to
      entry, it would facilitate cost-benefit studies of deferral or interventions.
      These analyses were undertaken to determine if a 5-minute step test conducted
      before entry identified women at increased risk. METHODS: A prospective study was
      conducted of weight-qualified women entering the Army in 2005-2006, with analyses
      completed in 2011. At the pre-entry examination, information was collected on
      age, BMI, smoking, race, and activity level. Everyone took the step test. All
      outpatient medical encounters were captured, and stress fractures and other
      musculoskeletal injuries identified. Women with stress fractures and those with
      other musculoskeletal injuries were evaluated separately. RESULTS: 1568 women
      were included in the study; 109 developed stress fractures and 803 other
      musculoskeletal injury. Women who failed the step test had a 76% higher stress
      fracture incidence and a 35% higher incidence of other musculoskeletal injuries.
      There was effect modification between age and test failure for stress fracture.
      CONCLUSIONS: A step test that can be administered before military entry
      identifies women with increased incidence of stress fracture and other
      musculoskeletal injury. This test could be used pre-entry to defer or target high
      risk recruits for tailored fitness training before or after military entrance.

PMID- 22608381
TI  - Binge drinking intensity: a comparison of two measures.
AB  - BACKGROUND: Binge drinking (>= 4 drinks for women; >= 5 drinks for men, per
      occasion) is responsible for more than half of the estimated 80,000 U.S. deaths
      annually and three-quarters of the $223.5 billion in costs in 2006. Binge
      drinking prevalence is assessed more commonly than binge drinking intensity
      (i.e., number of drinks consumed per binge episode). Risk of binge drinking
      related harm increases with intensity, and thus it is important to monitor. The
      largest number of drinks consumed is assessed in health surveys, but its
      usefulness for assessing binge intensity is unknown. PURPOSE: To assess the
      agreement between two potential measures of binge drinking intensity: the largest
      number of drinks consumed by binge drinkers (maximum-drinks) and the total number
      of drinks consumed during their most recent binge episode (drinks-per-binge).
      METHODS: Data were analyzed from 7909 adult binge drinkers from 14 states
      responding to the 2008 Behavioral Risk Factor Surveillance System (BRFSS) binge
      drinking module. Mean and median drinks-per-binge from that module were compared
      to mean and median maximum-drinks. Analyses were conducted in 2010-2011. RESULTS:
      Mean (8.2) and median (5.9) maximum-drinks were strongly correlated with mean
      (7.4) and median (5.4) drinks-per-binge (r=0.57). These measures were also
      strongly correlated across most sociodemographic and drinking categories overall
      and within states. CONCLUSIONS: The maximum-drinks consumed by binge drinkers is
      a practical method for assessing binge drinking intensity and thus can be used to
      plan and evaluate Community Guide-recommended strategies for preventing binge
      drinking (e.g., increasing the price of alcoholic beverages and regulating
      alcohol outlet density).

PMID- 22608382
TI  - Role of video games in improving health-related outcomes: a systematic review.
AB  - CONTEXT: Video games represent a multibillion-dollar industry in the U.S.
      Although video gaming has been associated with many negative health consequences,
      it also may be useful for therapeutic purposes. The goal of this study was to
      determine whether video games may be useful in improving health outcomes.
      EVIDENCE ACQUISITION: Literature searches were performed in February 2010 in six
      databases: the Center on Media and Child Health Database of Research, MEDLINE,
      CINAHL, PsycINFO, EMBASE, and the Cochrane Central Register of Controlled Trials.
      Reference lists were hand-searched to identify additional studies. Only RCTs that
      tested the effect of video games on a positive, clinically relevant health
      consequence were included. Study selection criteria were strictly defined and
      applied by two researchers working independently. Study background information
      (e.g., location, funding source); sample data (e.g., number of study
      participants, demographics); intervention and control details; outcomes data; and
      quality measures were abstracted independently by two researchers. EVIDENCE
      SYNTHESIS: Of 1452 articles retrieved using the current search strategy, 38 met
      all criteria for inclusion. Eligible studies used video games to provide physical
      therapy, psychological therapy, improved disease self-management, health
      education, distraction from discomfort, increased physical activity, and skills
      training for clinicians. Among the 38 studies, a total of 195 health outcomes
      were examined. Video games improved 69% of psychological therapy outcomes, 59% of
      physical therapy outcomes, 50% of physical activity outcomes, 46% of clinician
      skills outcomes, 42% of health education outcomes, 42% of pain distraction
      outcomes, and 37% of disease self-management outcomes. Study quality was
      generally poor; for example, two thirds (66%) of studies had follow-up periods of
      <12 weeks, and only 11% of studies blinded researchers. CONCLUSIONS: There is
      potential promise for video games to improve health outcomes, particularly in the
      areas of psychological therapy and physical therapy. RCTs with appropriate rigor
      will help build evidence in this emerging area.

PMID- 22608383
TI  - A population approach to precision medicine.
AB  - The term P4 medicine is used to denote an evolving field of medicine that uses
      systems biology approaches and information technologies to enhance wellness
      rather than just treat disease. Its four components include predictive,
      preventive, personalized, and participatory medicine. In the current paper, it is
      argued that in order to fulfill the promise of P4 medicine, a "fifth P" must be
      integrated-the population perspective-into each of the other four components. A
      population perspective integrates predictive medicine into the ecologic model of
      health; applies principles of population screening to preventive medicine; uses
      evidence-based practice to personalize medicine; and grounds participatory
      medicine on the three core functions of public health: assessment, policy
      development, and assurance. Population sciences-including epidemiology;
      behavioral, social, and communication sciences; and health economics,
      implementation science, and outcomes research-are needed to show the value of P4
      medicine. Balanced strategies that implement both population- and individual
      level interventions can best maximize health benefits, minimize harm, and avoid
      unnecessary healthcare costs.

PMID- 22608384
TI  - An evidence integration triangle for aligning science with policy and practice.
AB  - Over-reliance on decontextualized, standardized implementation of efficacy
      evidence has contributed to slow integration of evidence-based interventions into
      health policy and practice. This article describes an "evidence integration
      triangle" (EIT) to guide translation, implementation, prevention efforts,
      comparative effectiveness research, funding, and policymaking. The EIT emphasizes
      interactions among three related components needed for effective evidence
      implementation: (1) practical evidence-based interventions; (2) pragmatic,
      longitudinal measures of progress; and (3) participatory implementation
      processes. At the center of the EIT is active engagement of key stakeholders and
      scientific evidence and attention to the context in which a program is
      implemented. The EIT model is a straightforward framework to guide practice,
      research, and policy toward greater effectiveness and is designed to be
      applicable across multiple levels-from individual-focused and patient-provider
      interventions, to health systems and policy-level change initiatives.

PMID- 22608385
TI  - Efficacy of smoking-cessation interventions for young adults: a meta-analysis.
AB  - CONTEXT: Approximately 22% of U.S. young adults (aged 18-24 years) are smokers.
      Young adults typically display an interest in quitting, but it is unknown whether
      the evidence-based cessation programs designed for adults will be equally
      effective for young adults. This meta-analysis investigated the efficacy of
      smoking-cessation programs for this population. EVIDENCE ACQUISITION: In 2009
      2011, studies published between 2004 and 2008 that investigated smoking cessation
      were first found through the DHHS Clinical Practice Guidelines for Treating
      Tobacco Use and Dependence as well as a PubMed search (2009-2010) and were then
      subjected to a rigorous inclusion process. Authors were contacted to glean raw
      data for young adults. Fourteen studies provided data that were coded for
      descriptive information and aggregated using the Comprehensive Meta-Analysis,
      version 2.0. EVIDENCE SYNTHESIS: Among young adults, any type of intervention was
      more effective in producing successful smoking cessation than the control. This
      was the case for intent-to-treat analyses as well as complete cases. When
      interventions were effective for the larger adult sample, they were also
      effective for the younger adult sample. CONCLUSIONS: Although young adults tend
      to underutilize evidence-based cessation treatments, the current meta-analysis
      showed that these treatments should be as effective for young adults as they are
      for the general adult population. Thus, it may be useful to focus on motivating
      young adults to seek cessation treatment to increase utilization.

PMID- 22608387
TI  - The Jamaican historical experience of the impact of educational interventions on
      sickle cell disease child mortality.

PMID- 22608388
TI  - Newborn screening in Jamaica: inaccurate reference.

PMID- 22608389
TI  - New substituted 4H-chromenes as anticancer agents.
AB  - As a continuation of our efforts to discover and develop small molecules as
      anticancer agents, we identified GRI-394837 as an initial hit from similarity
      search on RGD and its analogs. Based on GRI-394837, we designed and synthesized a
      focused set of novel chromenes (4a-e) in a single step using microwave method.
      All five compounds showed activity in the nanomolar range (IC(50): 7.4-640 nM) in
      two melanoma, three prostate and four glioma cancer cell lines. The chromene 4e
      is active against all the cell lines and particularly against the A172 human
      glioma cell line (IC(50): 7.4 nM). Interestingly, in vitro tubulin polymerization
      assay shows 4e to be a weak tubulin polymerization inhibitor but it shows very
      strong cytotoxicity in cellular assays, therefore there must be additional
      unknown mechanism(s) for the anticancer activity. Additionally, the strong
      antiproliferative activity was verified by one of the selected chromene (4a) by
      the NCI 60 cell line screen. These results strongly suggest that the novel
      chromenes could be further developed as a potential therapeutic agent for a
      variety of aggressive cancers.

PMID- 22608390
TI  - Synthesis and anti-leishmanial activity of 1-aryl-beta-carboline derivatives
      against Leishmania donovani.
AB  - beta-carbolines from various natural and synthetic sources have been known to
      show diverse biological activities. As a part of our current ongoing project to
      search for potent natural product-derived anti-leishmanial compounds, we have
      synthesized a series of substituted 1-aryl-beta-carboline derivatives. A total of
      22 compounds were synthesized and tested in vitro against Leishmania donovani,
      out of which 6 compounds (4, 5, 10, 11, 19 and 22) showed notably more activity
      than the standard miltefosine (IC(50) 12.07+/-0.82 MUM), with compound 4 being
      the most potent (IC(50) 2.16+/-0.26 MUM).

PMID- 22608391
TI  - Towards a KCC2 blocker pharmacophore model.
AB  - A multi-disciplinary approach was used to identify the first pharmacophore model
      for KCC2 blockers: several physico-chemical studies such as XRD and NMR were
      combined to molecular modelling techniques, SAR analysis and synthesis of
      constrained analogues in order to determine a minimal conformational space
      regrouping few potential bioactive conformations. These conformations were
      further compared to the conformational space of a different series of KCC2
      blockers in order to identify the common pharmacophoric features. The synthesis
      of more potent analogues in this second series confirmed the usefulness of this
      KCC2 blocker pharmacophore model.

PMID- 22608392
TI  - Synthesis of chalcone derivatives as potential anti-diabetic agents.
AB  - Chalcones bearing electron donating or electron withdrawing substitutions were
      prepared and their glucose uptake activity was evaluated. Chalcone derivatives
      were synthesized in one step protocol with high purity and yield. Chalcones with
      chloro, bromo, iodo and hydroxy substitutions at position 2 on A-ring exhibited
      the highest activity with glucose medium concentration (210 to 236 mg/dl)
      compared to pioglitazone and rosiglitazone (230 and 263 mg/dl, respectively).
      Also chalcones with iodo substitution at position 3 on A-ring were comparably
      active (<=238 mg/dl). The structure-activity relationship of the tested chalcones
      was studied and the findings were supported statistically.

PMID- 22608393
TI  - Pyrazole and pyrimidine phenylacylsulfonamides as dual Bcl-2/Bcl-xL antagonists.
AB  - 5-Butyl-1,4-diphenyl pyrazole and 2-amino-5-chloro pyrimidine acylsulfonamides
      were developed as potent dual antagonists of Bcl-2 and Bcl-xL. Compounds were
      optimized for binding to the I88, L92, I95, and F99 pockets normally occupied by
      pro-apoptotic protein Bim. An X-ray crystal structure confirmed the proposed
      binding mode. Observation of cytochrome c release from isolated mitochondria in
      MV-411 cells provides further evidence of target inhibition. Compounds
      demonstrated submicromolar antiproliferative activity in Bcl-2/Bcl-xL dependent
      cell lines.

PMID- 22608394
TI  - [How to assess competence of the critical ill patient? Ever closer to the
      answer].

PMID- 22608395
TI  - [Donation following controlled cardiac death (Maastricht type III). Rapid surgery
      without premortem cannulation as an alternative].

PMID- 22608396
TI  - The diagnostic value of dynamic contrast-enhanced MRI for thyroid tumors.
AB  - BACKGROUND AND PURPOSE: The exact place for dynamic contrast-enhanced magnetic
      resonance imaging (DCE-MRI) in the diagnosis and management of thyroid tumors is
      still under debate. We performed the study to analyze and compare the parameters
      generated from DCE-MRI for thyroid lesions. MATERIALS AND METHODS: For each
      thyroid lesion, time intensity curves (TIC), time of peak enhancement (Tpeak),
      maximum enhancement ratio (ERmax) and maximum rise slope (Slopemax) were plotted
      and calculated. Receiver operator characteristics (ROC) analysis was conducted to
      assess the diagnostic ability and appropriate cut-off value. The area under the
      ROC curve (AUC) and the confidence intervals (CIs) were also assessed. RESULTS:
      Forty-two patients were consecutively included. All 21 lesions demonstrated the
      rapid inflow and washout pattern (type-I) were benign. The 12 cases with delayed
      inflow pattern (type-III) were all malignant. When compared with the benign
      lesions, the thyroid carcinoma showed significantly lower Slopemax and higher
      Tpeak (P<0.05). No statistical difference of ERmax was found between malignant
      and benign ones (P=0.15). The AUC of ERmax, Slopemax and Tpeak in differentiating
      benign thyroid lesions from malignant ones were 0.63, 0.93 and 1, respectively.
      The ERmax cut-off value of 73.86 (sensitivity, 71.4%; specificity, 64.3%),
      Slopemax cut-off value of 2.4126 (sensitivity, 92.9%; specificity, 82.1%) and
      Tpeak value of 28 (sensitivity, 100%; specificity, 100%) offered the best
      diagnostic performances. CONCLUSIONS: DCE-MRI, especially the pattern of TIC and
      the value of Slopemax and Tpeak, could be helpful in differentiating thyroid
      carcinoma from benign thyroid lesions.

PMID- 22608397
TI  - Could ultrasonic elastography help the diagnosis of small (<=2 cm) breast cancer
      with the usage of sonographic BI-RADS classification?
AB  - OBJECTIVES: To evaluate the additive value of ultrasound strain elastography
      (USE) to BI-RADS for the differentiation of benign and malignant breast small
      lesions. METHODS: Breast masses (<=2 cm) with histological diagnosis examined by
      ultrasonography and USE in our department from April 2004 to December 2009 were
      reviewed. Conventional B-mode ultrasound findings were classified according to
      the BI-RADS classification. USE findings were classified according to the 5-point
      scale. Histological diagnosis was used as the reference standard. RESULTS: 401
      (246 benign (61.3%), 155 malignant (38.7%)) from 370 consecutive patients were
      included in the study. Sensitivity and specificity were 90.3%, 68.3% for BI-RADS;
      72.3%, 91.9% for USE. The sensitivity of BI-RADS was better than that of USE
      (P<0.05), while the specificity of USE was better than that of BI-RADS (P<0.05).
      A revised BI-RADS combined with USE results was proposed in this study.
      Sensitivity and specificity were 83.9% and 87.8% for revised BI-RADS. The
      diagnostic performance of revised BI-RADS was better than BI-RADS (P<0.05).
      CONCLUSIONS: USE could give BI-RADS some help in the differentiation of benign
      and malignant breast small lesions. The addition of elastography to BI-RADS could
      improve the diagnostic performance in <2 cm lesions.

PMID- 22608398
TI  - "Focal thyroid inferno" on color Doppler ultrasonography: a specific feature of
      focal Hashimoto's thyroiditis.
AB  - PURPOSE: To evaluate color-Doppler features predictive of focal Hashimoto's
      thyroiditis. MATERIALS AND METHODS: A total of 521 patients with 561 thyroid
      nodules that underwent surgeries or gun biopsies were included in this study.
      These nodules were divided into three groups: focal Hashimoto's thyroiditis (104
      nodules in 101 patients), benignity other than focal Hashimoto's thyroiditis (73
      nodules in 70 patients), and malignancy (358 nodules in 350 patients). On color
      Doppler sonography, four vascularity types were determined as: hypovascularity,
      marked internal flow, marked peripheral flow and focal thyroid inferno. The chi2
      test was performed to seek the potential vascularity type with the predictive
      ability of certain thyroid pathology. Furthermore, the gray-scale features of
      each nodule were also studied. RESULTS: The vascularity type I (hypovascularity)
      was more often seen in focal Hashimoto's thyroiditis than other benignity and
      malignancy (46% vs. 20.5% and 19%). While the type II (marked internal flow)
      showed the opposite tendency (26.9% [focal Hashimoto's thyroiditis] vs. 45.2%
      [other benignity] and 52.8% [malignancy]). However, type III (marked peripheral
      flow) was unable to predict any thyroid pathology. Importantly, type IV (focal
      thyroid inferno) was exclusive to focal Hashimoto's thyroiditis. All 8 type IV
      nodules appeared to be solid, hypoechoic, and well-defined. Using "focal thyroid
      inferno" as an indicator of FHT, the diagnostic sensitivity and specificity were
      7.7% and 100% respectively. CONCLUSIONS: The vascularity type of "focal thyroid
      inferno" is specific for focal Hashimoto thyroiditis. Recognition of this
      particular feature may avoid unnecessary interventional procedures for some solid
      hypoechoic thyroid nodules suspicious of malignancy.

PMID- 22608399
TI  - Occurrence of pharmaceutical compounds in wastewater and sludge from wastewater
      treatment plants: removal and ecotoxicological impact of wastewater discharges
      and sludge disposal.
AB  - The occurrence of sixteen pharmaceutically active compounds in influent and
      effluent wastewater and in primary, secondary and digested sludge in one-year
      period has been evaluated. Solid-water partition coefficients (Kd) were
      calculated to evaluate the efficiency of removal of these compounds from
      wastewater by sorption onto sludge. The ecotoxicological risk to aquatic and
      terrestrial ecosystems, due to wastewater discharges to the receiving streams and
      to the application of digested sludge as fertilizer onto soils, was also
      evaluated. Twelve of the pharmaceuticals were detected in wastewater at mean
      concentrations from 0.1 to 32 MUg/L. All the compounds found in wastewater were
      also found in sewage sludge, except diclofenac, at mean concentrations from 8.1
      to 2206 MUg/kg dm. Ibuprofen, salicylic acid, gemfibrozil and caffeine were the
      compounds at the highest concentrations. LogKd values were between 1.17
      (naproxen) and 3.48 (carbamazepine). The highest ecotoxicological risk in
      effluent wastewater and digested sludge is due to ibuprofen (risk quotient (RQ):
      3.2 and 4.4, respectively), 17alpha-ethinylestradiol (RQ: 12 and 22,
      respectively) and 17beta-estradiol (RQ: 12 and 359, respectively).
      Ecotoxicological risk after wastewater discharge and sludge disposal is limited
      to the presence of 17beta-estradiol in digested-sludge amended soil (RQ: 2.7).

PMID- 22608400
TI  - Two-stage bile preparation with acetone for recovery of fluorescent aromatic
      compounds (FACs).
AB  - In this study we sought to optimize recovery of fluorescent aromatic compounds
      (FACs) from the bile of African catfish (Clarias gariepinus) injected with
      10mg/kg benzo[a]pyrene (BaP). Fractions of pooled bile were hydrolyzed, combined
      with ten volumes of methanol, ethanol, acetonitrile, or acetone, centrifuged and
      supernatants were analyzed by high-performance liquid chromatography with
      fluorescent detection (HPLC/FL). As well, to test whether FACs were being lost in
      solids from the centrifugation, pellets were resuspended, hydrolyzed and mixed
      with six volumes of the organic solvent that produced best FAC recovery from the
      supernatant, and subjected to HPLC/FL. Highest FAC concentrations were obtained
      with 2000MUl and 1250MUl acetone for supernatants and resuspended pellets
      respectively. FACs concentrations were negatively correlated with biliary protein
      content but were unaffected by addition of bovine serum albumin (BSA) followed by
      no incubation indicating that the presence of proteins in the biliary mixture
      does not simply interfere with detection of FACs. In another experiment,
      efficiency of acetone addition was compared to two different liquid-liquid
      extractions (L-LEs). Acetone additions provided significantly higher biliary FACs
      than the L-LE methods. The new two-stage bile preparation with acetone is an
      efficient, inexpensive and easily performed method.

PMID- 22608401
TI  - Multimodality therapy offers a chance for cure in patients with pancreatic
      adenocarcinoma deemed unresectable at first operative exploration.
AB  - BACKGROUND: Patients identified at surgical exploration with unresectable
      pancreatic ductal adenocarcinoma receive palliative, noncurative therapy. We
      hypothesized that accurate radiographic restaging, multimodality treatment, and
      advanced surgical technique can offer patients deemed unresectable at previous
      exploration the possibility for curative salvage pancreatectomy. STUDY DESIGN:
      Review of a prospectively maintained pancreatic ductal adenocarcinoma database
      identified all patients (1990 to 2010) evaluated after being deemed unresectable
      at first exploration elsewhere. Referring hospitals were categorized per National
      Cancer Data Base criteria as academic, community, or international. Patients were
      restaged using objective imaging (CT) criteria and classified based on anatomic
      resectability. Clinicopathologic factors and cancer-related outcomes were
      assessed. RESULTS: We evaluated 88 patients who underwent previously unsuccessful
      resection attempts at academic (n = 50), community (n = 25), and international (n
      = 13) centers. Radiographic restaging confirmed that 7 (8%) patient tumors were
      locally advanced and unresectable, but 81 (92%) were resectable (n = 61) or
      borderline resectable (n = 20). Using a surgery first (9%) or preoperative
      chemoradiation (91%) approach, successful reoperative pancreatectomy was
      performed in 66 (81%) patients, with 94% receiving R0 resections. Vascular
      resection/reconstruction was required in 30 (46%) patients and 50 (76%) required
      complex revision of previously created biliary/gastrointestinal bypass. The major
      complication rate was 20% and 3 (4.5%) patients died perioperatively. Median
      overall survival was 29.6 months for successfully resected patients vs 10.6 and
      5.1 months (p < 0.0001) for those patients with locally advanced unresectable
      disease at initial referral or in whom metastatic disease developed before
      resection, respectively. CONCLUSIONS: In this very selected cohort of high-risk
      patients, the majority had anatomically resectable tumors on restaging. Accurate
      radiographic restaging, a multimodality treatment strategy, and advanced surgical
      techniques can provide an opportunity for cure in a substantial proportion of
      select patients who were deemed unresectable at exploration.

PMID- 22608402
TI  - Comparison of outcomes of breast conserving therapy in multifocal and unifocal
      invasive breast cancer.
AB  - BACKGROUND: There is controversy about whether breast conserving therapy (BCT)
      should be contraindicated in multifocal (MF) breast cancer. Few studies have
      reported on the oncologic safety of BCT in MF breast cancer. STUDY DESIGN: We
      reviewed a prospective database of 1,169 women with invasive breast cancer who
      were treated with segmentectomy and whole breast irradiation from 1991 through
      2009 and followed at our institution. Multifocal breast cancer was defined as 2
      or more distinct tumors excised with a single incision or segmentectomy. We
      compared 2 groups, MF and unifocal breast cancer patients, with respect to
      demographics, tumor characteristics, adjuvant systemic therapy, local recurrence
      (LR), disease-free survival (DFS), and overall survival (OS). RESULTS: One
      hundred sixty-four patients with MF and 999 with unifocal invasive breast cancer
      were treated with BCT. Median follow-up was 112 months. Compared with the
      unifocal group, patients in the MF group had higher 10-year LR (0.6% vs 6.1%, p <
      0.001) and lower 10-year DFS (97.7% vs 89.3%, p < 0.001) and OS (98.4% vs 85.8%,
      p < 0.001). On multivariable analysis, multifocality was independently
      significantly associated with local recurrence-free survival (LRFS), DFS, and OS.
      CONCLUSIONS: Our data suggest that BCT in MF breast cancer is oncologically safe
      but may result in a slightly inferior outcome compared with BCT in unifocal
      breast cancer.

PMID- 22608403
TI  - Liver transplantation for hepatocellular carcinoma: long-term results suggest
      excellent outcomes.
AB  - BACKGROUND: Selected 5-year survival results after liver transplantation for
      hepatocellular carcinoma (HCC) have been reported to be 70%. Our hypothesis was
      that liver transplantation is effective for long-term cancer control for HCC.
      STUDY DESIGN: A 20-year retrospective review of a prospectively collected
      database was carried out. Demographic data and patient survival were calculated.
      RESULTS: There were 1,422 liver transplantations performed between January 1990
      and April 2011. Of these, 264 had HCC and 157 (59%) were pretreated with
      transarterial chemoembolization. Recipient age was 55.9 (+/- 7.9) years and 208
      (79%) of patients were male. The underlying disease was hepatitis C virus in 155
      (58.7%), hepatitis B virus in 16 (6%), alcohol in 21 (8%), and miscellaneous in
      the remaining 72 cases. The mean number of tumors was 1.8 (+/- 1.7) and the mean
      largest tumor diameter was 2.3 (+/- 1.3) cm in the explanted liver. One, 5, and
      10-year patient survival was 88.5%, 69.1%, and 40.5%, respectively; disease
      specific survival was 99.1%, 94.4% and 87.9%; and disease-free survival was
      86.0%, 64.6%, and 40.1%. One, 5, and 10-year graft survival was 87.3%, 68.0%, and
      41.8%. Nine (3.4%) patients required retransplantation; 75 patients (28.4%) have
      died, but only 10 of 75 (13.3%) died of recurrent HCC (3.7% of all HCC patients
      receiving a transplant) and 6 (8%) died of recurrent viral hepatitis. An
      additional 9 recipients developed recurrence (total HCC recurrence, n = 19 [7%]),
      4 of whom died of causes other than HCC. The remaining 5 are disease-free post
      treatment (mean 5.5 years after orthotopic liver transplantation). CONCLUSIONS:
      Orthotopic liver transplantation offers an effective treatment strategy for HCC
      in the setting of cirrhosis, even in the setting of hepatitis C virus.
      Hepatocellular carcinoma recurrence is uncommon in properly selected patients and
      disease-specific long-term survival approaches 90%.

PMID- 22608404
TI  - Neural representations of unfamiliar objects are modulated by sensorimotor
      experience.
AB  - Sensory/functional accounts of semantic memory organization emphasize that object
      representations in the brain reflect the modalities involved in object knowledge
      acquisition. The present study aimed to elucidate the impact of different types
      of object-related sensorimotor experience on the neural representations of novel
      objects. Sixteen subjects engaged in an object matching task while their brain
      activity was assessed with functional magnetic resonance imaging (fMRI), before
      and after they acquired knowledge about previously unfamiliar objects. In three
      training sessions subjects learned about object function, actively manipulating
      only one set of objects (manipulation training objects, MTO), and visually
      exploring a second set (visual training objects, VTO). A third object set served
      as control condition and was not part of the training (no training objects, NTO).
      While training-related activation increases were observed in the fronto-parietal
      cortex for both VTO and MTO, post training activity in the left inferior/middle
      frontal gyrus and the left posterior inferior parietal lobule was higher for MTO
      than VTO and NTO. As revealed by Dynamic Causal Modeling of effective
      connectivity between the regions with enhanced post training activity, these
      effects were likely caused, respectively, by a down-regulation of a fronto
      parietal tool use network in response to VTO, and by an increased connectivity
      for MTO. This pattern of findings indicates that the modalities involved in
      sensorimotor experience influence the formation of neural representations of
      objects in semantic memory, with manipulation experience specifically yielding
      higher activity in regions of the fronto-parietal cortex.

PMID- 22608405
TI  - Genome analysis of Rift Valley fever virus, Mayotte.
AB  - As further confirmation of a first human case of Rift Valley fever in 2007 in
      Comoros, we isolated Rift Valley fever virus in suspected human cases. These
      viruses are genetically closely linked to the 2006-2007 isolates from Kenya.

PMID- 22608406
TI  - Links between alcohol and other drug problems and maltreatment among adolescent
      girls: perceived discrimination, ethnic identity, and ethnic orientation as
      moderators.
AB  - OBJECTIVES: This study examined the links between maltreatment, posttraumatic
      stress symptoms, ethnicity-specific factors (i.e., perceived discrimination,
      ethnic identity, and ethnic orientation), and alcohol and/or other drug (AOD)
      problems among adolescent girls. METHODS: These relations were examined using
      archived data from a community sample of 168 Black and Hispanic adolescent girls
      who participated in a school-based substance use intervention. RESULTS: The
      results revealed that maltreatment was linked to AOD problems, but only through
      its relation with posttraumatic stress symptoms; maltreatment was positively
      related to posttraumatic stress symptoms, which were positively related to AOD
      problems. Both perceived discrimination and ethnic orientation were significant
      moderators. Specifically, greater perceived discrimination was associated with an
      increased effect of maltreatment on posttraumatic stress symptoms. Ethnic
      orientation demonstrated protective properties in the relation between
      maltreatment and AOD problem severity, such that the effect of maltreatment on
      AOD problem severity was less for girls with average to high ethnic orientation
      compared to girls with low ethnic orientation. CONCLUSIONS: The findings of this
      study underscore the importance of developing interventions for Black and
      Hispanic girls that target maltreatment and AOD use concurrently and address
      ethnicity-specific factors.

PMID- 22608407
TI  - Stability-indicating capillary zone electrophoresis method for the assessment of
      recombinant human granulocyte-macrophage colony-stimulating factor and its
      correlation with reversed-phase liquid chromatography method and bioassay.
AB  - A stability-indicating capillary zone electrophoresis (CZE) method was validated
      for the analysis of granulocyte-macrophage colony-stimulating factor (rhGM-CSF)
      using leuprorelin acetate (LA), as internal standard (IS). A fused-silica
      capillary (75 MUm i.d.; effective length, 72 cm) was used at 25  degrees C; the
      applied voltage was 12 kV. The background electrolyte solution consisted of 50mM
      di-sodium hydrogen phosphate solution at pH 8.8. Injections were performed using
      a pressure mode at 50 mbar for 9s, with detection by photodiode array detector
      set at 200 nm. Specificity and stability-indicating capability were established
      in degradation studies, which also showed that there was no interference of the
      excipients. The method was linear over the concentration range of 2.5-200 MUg mL(
      1) (r(2)=0.9995) and the limit of detection (LOD) and limit of quantitation (LOQ)
      were 0.79 MUg mL(-1) and 2.5 MUg mL(-1), respectively. The accuracy was 99.14%
      with bias lower than 1.40%. The method was applied to the quantitative analysis
      of biopharmaceutical formulations, and the results were correlated to those of a
      validated reversed-phase LC method (RP-LC), and an in vitro bioassay, showing non
      significant differences (p>0.05).

PMID- 22608408
TI  - On the chemical identification and determination of flavonoids in solid-state.
AB  - The paper presented with qualitative and quantitative analysis of alkaloids in
      solid-state, using the excitations within the THz-spectroscopic region of 300-30
      cm(-1) (9.00-0.9 THz). Series of nine plant flavonoids (FLs) and their mixtures
      were analyzed both qualitatively and quantitatively. For first time in the
      literature was reported the quantitative analysis of alkaloids and their mixtures
      within the THz-region using the solid-state Raman spectroscopy, and matrix
      assisted laser desorption/ionization (MALDI) mass spectrometry (MS). The
      calibration and validation, concentration limit of detection (LOD), limit of
      quantification (LOQ), and linearity limit (LL) were obtained. The chemometric
      nonlinear and linear approaches for analysis and interpretation of the quantities
      were applied. The results obtained were compared with a parallel QA, using the
      calibrated and validated HPLC electrospray ionization (ESI) mass spectrometric
      method, electronic absorption (EAs) and CD spectroscopy. The metrology, including
      accuracy, measurement repeatability (intra-serial precision condition of
      measurement), measurement precision, trueness of the measurement, and
      reproducibility of the measurement, measurement bias and errors of the
      measurements were discussed.

PMID- 22608409
TI  - An LC method for the analysis of phosphatidylcholine hydrolysis products and its
      application to the monitoring of the acyl migration process.
AB  - An assay for quantitative analysis of phosphatidylcholine (1,2-dipalmitoyl-sn
      glycero-3-phosphocholine) and its hydrolysis products: 1-hydroxy-2-palmitoyl-sn
      glycero-3-phosphocholine and 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphocholine,
      sn-glycero-3-phosphocholine and palmitic acid using high-performance liquid
      chromatography with charge aerosol detector (CAD) was developed. The separation
      of the compounds of interest was achieved on a reversed-phase/hydrophilic
      interaction stationary phase with a mobile phase consisting of
      acetonitrile:methanol:10mM ammonium acetate solution. The method was applied to
      control the acyl migration process of LPC regioisomers in the most common
      solvents used in the synthesis or modification of PC.

PMID- 22608410
TI  - A Pt layer/Pt disk electrode configuration to evaluate respiration and alkaline
      phosphatase activities of mouse embryoid bodies.
AB  - A Pt layer/Pt disk electrode configuration was used as a scanning electrochemical
      microscopy (SECM) probe. The glass seal part of the insulator was covered with a
      Pt layer to form an exposed pseudo reference electrode. In a HEPES-based medium
      at pH 7.5, the half-wave potential (E(1/2)) for [Fe(CN)(6)](4-) oxidation and
      O(2) reduction measured versus the internal Pt pseudo reference was shifted by
      about -0.2V, compared with the E(1/2) measured versus the external Ag/AgCl
      reference electrode. The shape and the current of the cyclic voltammograms (CVs)
      did not change notably over time, indicating that the Pt layer is sufficiently
      stable to be used as an integrated pseudo reference for voltammetric
      measurements. To demonstrate the suitability for SECM applications, the Pt/Pt
      probe configuration was used for measuring the oxygen consumption and the
      alkaline phosphatase (ALP) activity of a single mouse embryoid body (mEB). Ten
      individual mEB samples were characterized to monitor the oxygen concentration
      profile. Oxygen reduction currents were monitored at -0.7 V versus the Pt pseudo
      reference and compared with those monitored at -0.5 V versus Ag/AgCl. The
      respiration rate of mEBs becomes greater with increasing cultivation dates. We
      have plotted the oxygen consumption rate (F(O(2))) of each mEB sample, measured
      versus the Pt layer and versus Ag/AgCl. The linearity of the plot was excellent
      (coefficient of determination R(2)=0.90). The slope of the least squares method
      was 1. In a 1.0mM p-aminophenylphospate (PAPP) HEPES buffer (pH 9.5) solution,
      APL activity of mEBs can be characterized, to monitor the p-aminophenol (PAP)
      oxidation current. ALP catalyzes the hydrolysis of PAPP to PAP. The E(1/2) for
      PAP oxidation measured versus the Pt layer was not shifted, compared with the
      E(1/2) versus Ag/AgCl. The mEB samples were characterized to monitor the PAP
      concentration profile. PAP oxidation currents were monitored at +0.3 V versus the
      Pt layer and compared with those monitored at +0.3 V versus Ag/AgCl. We have
      plotted the PAP production rate (F(PAP)) of each mEB sample, measured versus the
      Pt layer and versus Ag/AgCl. In this case, the linearity of the plot became
      slightly scattered, but it was found to be possible to evaluate ALP activities of
      mEB samples utilizing the Pt/Pt probe configuration. This type of probe is very
      useful because it is not necessary to insert a reference electrode into the
      measuring solution to obtain an electrical connection, and thus electrochemical
      measurement in a small volume becomes much easier.

PMID- 22608411
TI  - A simple and selective fluorometric assay for dopamine using a calcein blue-Fe2+
      complex fluorophore.
AB  - A novel fluorimetric assay for dopamine using calcein blue (CB) complexed with
      Fe(2+) ion as a chemical sensor is described. The fluorescence arising from CB of
      the CB-Fe(2+) complex is quenched by the Fe(2+) ion. When dopamine is added to a
      solution of the CB-Fe(2+) complex, a dopamine-Fe(2+) complex is formed as the
      result of a ligand exchange reaction between CB and dopamine which permits the
      fluorescence from CB to be recovered. The fluorescence intensity at the
      wavelength of 440 nm (at the excitation wavelength of 340 nm) was found to be
      proportional to the concentration of the dopamine added to the CB-Fe(2+) complex
      solution, which permits dopamine to be quantitatively determined. The selectivity
      for dopamine in the presence of other catecholamines and related compounds was
      good. The calibration curve for dopamine, determined using experimental data was
      successfully simulated based on the equilibrium of the ligand exchange reaction
      between CB and dopamine. The working range is from 50 MUM to 1mM and the limit of
      detection and limit of quantization are ca 10 MUM and 50 MUM, respectively. The
      assay is simple and economical, compared with conventional methods such as an
      enzyme-linked immunosorbent assay (ELISA).

PMID- 22608412
TI  - Simultaneous analysis of organochlorinated pesticides (OCPs) and polychlorinated
      biphenyls (PCBs) from marine samples using automated pressurized liquid
      extraction (PLE) and Power PrepTM clean-up.
AB  - An automated pressurized liquid extraction (PLE) method followed by Power PrepTM
      clean-up was developed for organochlorinated pesticide (OCP) and polychlorinated
      biphenyl (PCB) analysis in environmental marine samples of fish, squid, bivalves,
      shells, octopus and shrimp. OCPs and PCBs were simultaneously determined in a
      single chromatographic run using gas chromatography-mass spectrometry-negative
      chemical ionization (GC-MS-NCI). About 5 g of each biological marine sample was
      mixed with anhydrous sodium sulphate and placed in the extraction cell of the PLE
      system. PLE is controlled by means of a PC using DMS 6000 software. Purification
      of the extract was accomplished using automated Power PrepTM clean-up with a pre
      packed disposable silica column (6 g) supplied by Fluid Management Systems (FMS).
      All OCPs and PCBs were eluted from the silica column using two types of solvent:
      80 mL of hexane and a 50 mL mixture of hexane and dichloromethane (1:1). A wide
      variety of fish and shellfish were collected from the fish market and analyzed
      using this method. The total PCB concentrations were 2.53, 0.25, 0.24, 0.24, 0.17
      and 1.38 ng g(-1) (w/w) for fish, squid, bivalves, shells, octopus and shrimp,
      respectively, and the corresponding total OCP concentrations were 30.47, 2.86,
      0.92, 10.72, 5.13 and 18.39 ng g(-1) (w/w). Lipids were removed using an SX-3 Bio
      Beads gel permeation chromatography (GPC) column. Analytical criteria such as
      recovery, reproducibility and repeatability were evaluated through a range of
      biological matrices.

PMID- 22608413
TI  - Determination of metal impurities in advanced lead zirconate titanate ceramics by
      axial view mode inductively coupled plasma optical emission spectrometry.
AB  - An inductively coupled plasma optical emission spectrometry quantification method
      for the determination of Al, Ca, Cr Cu, Fe, Mn, Mg, Ni, Zn, Ba, K, In and Co in
      lead zirconate-titanate (PZT) ceramics, modified with strontium and chromium, was
      developed. Total digestion of ceramics was achieved with a HNO(3), H(2)O(2) and
      HF (ac) mixture by using a microwave furnace. The sensitivity of the net signal
      intensity respect to radiofrequency power (P) and nebulizer argon flow (F(N))
      variations was strongly dependent of the total excitation energy of line (TEE).
      For lines with TEE near metastable atoms and ions of argon, an increment of the
      sensitivities to P and F(N) variation was observed. At robust plasma conditions
      the matrix effect was reduced for all matrices and analytes considered. The
      precision of analysis ranged from 3 to 13%, whereas the analytes recoveries in
      the spiked samples varied, mostly, from 90 to 110%. The detection limits of
      studied elements were from 0.004 to 10 mg kg(-1).

PMID- 22608414
TI  - An integrated electrochemical device based on immunochromatographic test strip
      and enzyme labels for sensitive detection of disease-related biomarkers.
AB  - A novel electrochemical biosensing device that integrates an
      immunochromatographic test strip and a screen-printed electrode (SPE) connected
      to a portable electrochemical analyzer was presented for rapid, sensitive, and
      quantitative detection of disease-related biomarker in human blood samples. The
      principle of the sensor is based on sandwich immunoreactions between a biomarker
      and a pair of its antibodies on the test strip, followed by highly sensitive
      square-wave voltammetry (SWV) detection. Horseradish peroxidase (HRP) was used as
      a signal reporter for electrochemical readout. Hepatitis B surface antigen
      (HBsAg) was employed as a model protein biomarker to demonstrate the analytical
      performance of the sensor in this study. Some critical parameters governing the
      performance of the sensor were investigated in detail. Under optimal conditions,
      this sensor was capable of detecting a minimum of 0.3 ng mL(-1) (S/N=3) HBsAg
      with a wide linear concentration range from 1 to 500 ng mL(-1). The sensor was
      further utilized to detect HBsAg spiked in human plasma with an average recovery
      of 91.3%. In comparison, a colorimetric immunochromatographic test strip assay
      (ITSA) was also conducted. The result shows that the SWV detection in the
      electrochemical sensor is much more sensitive for the quantitative determination
      of HBsAg than the colorimetric detection, indicating that such a sensor is a
      promising platform for rapid and sensitive point-of-care testing/screening of
      disease-related biomarkers in a large population.

PMID- 22608415
TI  - A rational route to the development of a competitive capillary electrophoresis
      immunoassay: assessment of the variables affecting the performances of a
      competitive capillary electrophoresis immunoassay for human serum albumin.
AB  - Affinity capillary electrophoresis is a powerful analytical tool to extract
      quantitative information about the binding properties of different interacting
      systems. The use of LIF detection makes the technique suitable for screening
      strong binding interactions. The non-equilibrium electrophoretic separations of
      pre-equilibrated mixtures of ligand and receptor are generally used for such
      strong molecular interactions allowing the assessment of capillary
      electrophoresis immunoassays, mostly in competitive formats. As the analytical
      performances of the assay strongly depend on the preservation of the binding
      properties during the separation, a rational route to assay development has to be
      followed to get the best conditions. The paper describes the steps followed to
      set-up a competitive immunoassay for human serum albumin (HSA) by using a labeled
      protein (HSA-FITC) and an anti-HSA polyclonal antiserum. A labeling degree of
      around 1 of the HSA-FITC conjugates is needed to get narrow electrophoretic peak
      while the titration curve is used to define the optimal antiserum dilution. An
      antiserum-labeled protein affinity constant of 1.34*10(7) M(-1) was measures in
      the selected separation conditions. Furthermore, in order to maximize the assay
      competition between the labeled and unlabelled HSA a short pre-incubation step of
      the antiserum with the unlabelled HSA (the analyte) was introduced to promote a
      sharp increase in assay sensitivity.

PMID- 22608416
TI  - Solidified floating organic drop microextraction combined with ETV-ICP-MS for the
      determination of trace heavy metals in environmental water samples.
AB  - A new method of solidified floating organic drop microextraction (SFODME)
      combined with electrothermal vaporization (ETV)-inductively coupled plasma mass
      spectrometry (ICP-MS) was developed for the determination of trace heavy metals
      in environmental water samples with sodium diethyldithiocarbamate (DDTC) as both
      chelating reagent in SFODME and chemical modifier in ETV. The factors affecting
      the microextraction efficiency were studied in detail and the optimal extraction
      conditions were established. Under the optimal conditions, the limits of
      detection (LODs) for SFODME-ETV-ICP-MS determination of Co, Pd, Cd, Hg, Pb and Bi
      were found to be 0.0060, 0.0091, 0.0020, 0.0041, 0.0170 and 0.0041 ng mL(-1),
      respectively, with the relative standard deviations (RSDs) of 2.8-10.0% (c=0.5 ng
      mL(-1), n=7). The developed method was successfully applied to the analysis of
      six target metals in Yangtze River and East Lake water samples with recoveries
      ranging from 77.7 to 119.1%. To validate the accuracy of the method, a certified
      reference material of Environmental Water (GSBZ50009-88) was analyzed and the
      determined values were in good agreement with the certified values.

PMID- 22608417
TI  - Simultaneous determination of chloropheniramine maleate and dextromethorphan
      hydrobromide in plasma sample by hollow fiber liquid phase microextraction and
      high performance liquid chromatography with the aid of chemometrics.
AB  - A simple and high sensitive technique based on three phase hollow fiber liquid
      phase microextraction (HF-LPME), optimized by using a four-variable experimental
      design and response surface methodology was performed to evaluate
      dextromethorphan hydrobromide (DEX) and chloropheniramine maleate (CLP)
      simultaneously in human plasma. The influence of source phase pH, HCl
      concentration of acceptor phase, time and salt addition were investigated. Under
      the optimized conditions analytes were extracted in their neutral form, pH 12.5
      and salt concentration 2% (w/v), through a supported liquid membrane (SLM) of
      hexadecane into the HCl 0.0005 mol L(-1) located inside the lumen of hollow fiber
      to be back extracted. The mass transfer of the analytes from the donor phase
      through the SLM into acceptor phase was driven by the pH gradient. Determination
      was accomplished by UV-high performance liquid chromatography with recoveries 92%
      and 84% for CLP and DEX, respectively. Linearity was obtained in the range of
      0.01-1000 MUg L(-1) (R(2)>0.994). The obtained enrichment factors (EFs) were 233
      276 for DEX and CLP respectively and limits of detection were 0.003 MUg L(-1)
      with RSDs below 6%. The method proposed acceptable values to determine CLP and
      DEX in plasma samples sensitively and accurately.

PMID- 22608418
TI  - Specific and targeted detection of viable Escherichia coli O157:H7 using a
      sensitive and reusable impedance biosensor with dose and time response studies.
AB  - A gold interdigitated microelectrode (IME) impedance biosensor was fabricated for
      the detection of viable Escherichia coli O157:H7. This sensor was fabricated
      using lithography techniques. The surface of the electrode was immobilized with
      anti-E. coli IgG antibodies. This approach is different from other studies where
      the change in impedance is measured in terms of growth of bacteria on the
      electrode, rather then the antibody/antigen bonding. The impedance values were
      recorded for frequency ranges between 100 Hz and 10 MHz. The working range of the
      dose response for this device was found to be between 2.5*10(4) CFU ml(-1) and
      2.5*10(7) CFU ml(-1). The time response studies indicated that antibody/antigen
      binding is not a function of time, but can decrease if excess times are allowed
      for binding. It was observed that the impedance values for 60 min
      antibody/antigen binding were higher than the impedance values for 120 min
      binding time. The main advantages of the reported device are that, it provides
      for both qualitative and quantitative detection in 3h while other impedance
      sensors reported earlier may take up to 24h for detection. If enrichment steps
      are required then it may take 3-4 days to infer the results. This sensor can be
      used to detect different types of bacteria by immobilizing the antigen specific
      antibody. Most of the sensors are not reusable since they either use enzymes or
      enrichment steps for detection but this device can be reused, following a
      cleaning protocol which is easy to follow. Each device was used at least five
      times. The simplicity of this sensor and the ease of fabrication make this sensor
      a useful alternate to the microfluidics and enzyme based impedance sensors, which
      are relatively more difficult to fabricate, need programmable fluidic injection
      pumps to push the sample through the channel, suffer from limitation of
      coagulation and are difficult to clean.

PMID- 22608419
TI  - Improving methodological aspects of the analysis of five regulated haloacetic
      acids in water samples by solid-phase extraction, ion-pair liquid chromatography
      and electrospray tandem mass spectrometry.
AB  - Haloacetic acids (HAAs) are organic pollutants originated from the drinking water
      disinfection process, which ought to be controlled and minimized. In this work a
      method for monitoring haloacetic acids (HAAs) in water samples is proposed, which
      can be used in quality control laboratories using the techniques most frequently
      available. Among its main advantages we may highlight its automated character,
      including minimal steps of sample preparation, and above all, its improved
      selectivity and sensitivity in the analysis of real samples. Five haloacetic
      acids (HAA5) were analyzed using solid-phase extraction (SPE) combined with ion
      pair liquid chromatography and tandem mass spectrometry. For the optimization of
      the chromatographic separation, two amines (triethylamine, TEA and dibutylamine,
      DBA) as ion pair reagents were compared, and a better selectivity and sensitivity
      was obtained using DBA, especially for monohaloacetic acids. SPE conditions were
      optimized using different polymeric adsorbents. The electrospray source
      parameters were studied for maximum precursor ion accumulation, while the
      collision cell energy of the triple quadrupole mass spectrometer was adjusted for
      optimum fragmentation. Precursor ions detected were deprotonated, dimeric and
      decarboxylated ions. The major product ions formed were: ionized halogen atom
      (chloride and bromide) and decarboxylated ions. After enrichment of the HAAs in
      Lichrolut EN adsorbent, the limits of detection obtained by LC-MS/MS analysis
      (between 0.04 and 0.3 ng mL(-1)) were comparable to those obtained by GC-MS after
      derivatization. Linearity with good correlation coefficients was obtained over
      two orders of magnitude irrespective of the compound. Adequate recoveries were
      achieved (60-102%), and the repeatability and intermediate precision were in the
      range of 2.4-6.6% and 3.8-14.8%, respectively. In order to demonstrate the
      usefulness of the method for routine HAAs monitoring, different types of water
      samples were analyzed. In swimming pool water samples the ?HAAs were determined
      between 76 and 154 ng mL(-1).

PMID- 22608420
TI  - Ion-selective electrodes based on L-tryptophan and L-tyrosine.
AB  - Novel ion-selective electrodes (ISEs) based on amino acids have been developed. L
      Tryptophan and L-tyrosine, which are amino acids, are employed as ionophores for
      solvent polymeric membrane electrodes. The proposed ISEs show rapid Nernstian
      responses for the Cu(2+) ion over the concentration ranges of 3.0*10(-4)-1.0*10(
      1) M. These ISEs exhibit comparatively good selectivity with respect to alkaline,
      alkaline earth, and some transition and heavy metal ions and the ammonium ion.
      The ISE based on tryptophan also indicates the Nernstian response for the
      benzylammonium ion.

PMID- 22608421
TI  - Dynamic layer-by-layer self-assembly of multi-walled carbon nanotubes on quartz
      wool for on-line separation of lysozyme in egg white.
AB  - The multi-walled carbon nanotubes (MWNTs) coated quartz wool (MWNTs/QW) prepared
      by dynamic layer-by-layer self-assembly was used as solid-phase extraction (SPE)
      absorbent for on-line separation and preconcentration of lysozyme in egg white.
      The coating procedures were performed continuously in a flow system operated by a
      set of sequential injection devices. The quartz wool was placed in a microcolumn
      forming a loose packing to guarantee the minimized flow impedance and the
      intimate contact between proteins and absorbent surface. Various parameters
      affecting SPE efficiency including the volume, pH, ionic strength and flow rate
      of sample and eluent were systematically studied. The feasibility of the proposed
      method was validated by successfully applied to the separation of lysozyme in egg
      white.

PMID- 22608422
TI  - A monosegmented flow-batch system for slow reaction kinetics: spectrophotometric
      determination of boron in plants.
AB  - This work introduces the monosegmented flow-batch (MSFB) analysis concept. This
      system combines favourable characteristics of both flow-batch and the
      monosegmented analysers, allowing use of the flow-batch system for slow reaction
      kinetics without impairing sensitivity or sampling throughput. The MSFB was
      evaluated during spectrophotometric determination of boron in plant extracts,
      which is a method that involves a slow reaction between boron and azomethine-H.
      All calibration solutions were prepared in-line, and all analytical processes
      completed by simply changing the operational parameters in the MSFB control
      software. The limit of detection was estimated at 0.008 mg L(-1). The
      measurements could be performed at a rate of 120 samples per hour with
      satisfactory precision. The proposed MSFB was successfully applied to analyse 10
      plant samples and the results are in agreement with the reference method at a 95%
      level of confidence.

PMID- 22608423
TI  - Preconcentration of trace amounts of methadone in human urine, plasma, saliva and
      sweat samples using dispersive liquid-liquid microextraction followed by high
      performance liquid chromatography.
AB  - A simple, rapid and efficient method for the preconcentration of methadone was
      developed using dispersive liquid-liquid microextraction (DLLME) followed by high
      performance liquid chromatography with ultra violet detection (HPLC-UV). The
      extraction method is based on the fast injection of a mixture of extracting and
      disperser solvents into the aqueous solution to form a cloudy ternary component
      solvent (aqueous solution:extracting solvent:disperser solvent) system. The
      extraction parameters such as nature and volume of extracting and disperser
      solvents, pH of sample, and extraction time were studied for optimization. Under
      the optimal conditions (extracting solvent: chloroform, 250 MUL; disperser
      solvent: methanol, 2.5 mL and pH of sample: 10.0) a linear calibration curve was
      obtained in the range of 0.5-5000 ng mL(-1) with r(2)=0.9995. To demonstrate
      analytical performance, figures of merits of the proposed method in four
      different biological matrices (urine, plasma, saliva and sweat) spiked with
      methadone were investigated. The limits of detection and quantification in these
      matrices were ranged from 4.90 to 24.85 ng mL(-1) and 16.32 to 82.75 ng mL(-1),
      respectively. The extraction recoveries were above 97% and the preconcentration
      factors of methadone in distilled water, urine, plasma, saliva, and sweat samples
      were 196.52, 10.03, 9.93, 1.97 and 1.99, respectively. While the precision for
      inter-day was <=6.43 (n=5), it was <=2.26 (n=5) for intra-day assay. Finally, the
      method was successfully applied in the determination of methadone in the human
      urine, plasma, saliva and sweat samples.

PMID- 22608424
TI  - Characterization of disposable optical sensors for heavy metal determination.
AB  - This paper presents the development, characterization and quality control of
      analytical methods based on the use of disposable optical sensors for
      determination of heavy metals. Chromogenic reagents such as 1-(2-pyridylazo)-2
      naphthol, (2-pyridylazo)resorcinol, Zincon, Ferrozine, and Chromazurol S were
      used to develop optical sensors of heavy metal ions found as contaminants in
      pharmaceutical substances and products, such as Zn(II), Cu(II), Ni(II), Fe(II),
      and Fe(III). The chromogenic reagents were immobilized in polymeric membranes by
      spin-coating from cocktails containing all reagents needed. The methods were
      prevalidated using a comprehensive quality control strategy based on a system of
      mathematical/statistical testing and diagnosis of each prevalidation step. This
      system involved characterization of analytical groups; checking of two limiting
      groups; testing of data homogeneity; recognition of outliers; and determination
      of analytical functions, limiting values, precision and accuracy. The
      prevalidation strategy demonstrated the reliability of the proposed method and
      pointed out some limitations. Combining the optical sensors with multicomponent
      linear regression allowed simultaneous determination of multiple metals in
      synthetic mixtures with different compositions. Good agreement between
      experimental and theoretical amounts of heavy metals in the mixtures was obtained
      for the majority of sensors and metals. Even better agreement was obtained
      between the experimental and theoretical total amounts of metals in the mixtures.
      The proposed analytical methods were successfully applied to the determination of
      zinc in pharmaceutical preparations of insulin and the determination of metal
      mixtures in a commercial nasal spray of isotonic seawater. The reliable and
      sensitive individual optical sensors developed in this study may be useful for
      designing a multimembrane optical tongue that with appropriate further
      optimization can be used for screening heavy metals in various matrices.

PMID- 22608425
TI  - Design of molecularly imprinted polymers for diphenylamine sensing.
AB  - A series of the polymers imprinted with diphenylamine (DPA) and respective non
      imprinted polymers were synthesized using precipitation polymerization.
      Synthesized polymers were characterized by Fourier Transform Infra-Red
      spectroscopy with Total Attenuated Reflectance (FTIR-ATR), Scanning Electron
      Microscopy (SEM) and equilibrium batch re-binding experiments. Influence of the
      synthesis conditions, namely monomer/template ratio and reaction duration, on the
      polymer binding capacity and selectivity towards aromatic compounds was
      investigated. Binding behavior of MIP was described using Freundlich isotherm.
      Significance of the effects of the synthesis conditions on the polymer properties
      was evaluated using ANOVA. MIPs synthesized at different conditions, which
      displayed different properties (binding capacity and selectivity), and respective
      non-imprinted polymers were employed for the fabrication of the potentiometric
      sensors. While sensors prepared using imprinted polymers had higher sensitivity
      and selectivity compared to the ones containing non-imprinted polymer, no
      difference was observed between sensors containing different imprinted polymers.
      No correspondence between polymers' characteristics obtained in the equilibrium
      re-binding studies and potentiometric behavior of the sensors based on the same
      polymers was observed. Therefore, equilibrium re-binding studies cannot be used
      for predicting sensor behavior.

PMID- 22608426
TI  - The loss of essential oil components induced by the Purge Time in the Pressurized
      Liquid Extraction (PLE) procedure of Cupressus sempervirens.
AB  - The influence of different Purge Times on the effectiveness of Pressurized Liquid
      Extraction (PLE) of volatile oil components from cypress plant matrix (Cupressus
      sempervirens) was investigated, applying solvents of diverse extraction
      efficiencies. The obtained results show the decrease of the mass yields of
      essential oil components as a result of increased Purge Time. The loss of
      extracted components depends on the extrahent type - the greatest mass yield loss
      occurred in the case of non-polar solvents, whereas the smallest was found in
      polar extracts. Comparisons of the PLE method with Sea Sand Disruption Method
      (SSDM), Matrix Solid-Phase Dispersion Method (MSPD) and Steam Distillation (SD)
      were performed to assess the method's accuracy. Independent of the solvent and
      Purge Time applied in the PLE process, the total mass yield was lower than the
      one obtained for simple, short and relatively cheap low-temperature matrix
      disruption procedures - MSPD and SSDM. Thus, in the case of volatile oils
      analysis, the application of these methods is advisable.

PMID- 22608427
TI  - Microwave-enhanced cold vapor generation for speciation analysis of mercury by
      atomic fluorescence spectrometry.
AB  - A new and simple cold vapor generation technique utilizing microwave irradiation
      coupled with atomic fluorescence spectrometry is developed for the speciation
      analysis of mercury in biological and geological samples. In the presence of
      formic acid, inorganic mercury (Hg(2+)) and total mercury (both Hg(2+) and
      methylmercury (MeHg)) can be converted to mercury cold vapor (Hg(0)) by microwave
      irradiation without and with H(2)O(2), respectively. The cold vapor was
      subsequently released from the liquid phase and rapidly transported to an atomic
      fluorescence spectrometer for the mercury detection. Optimum conditions for vapor
      generation as well as interferences from concomitant ions were carefully
      investigated. The conventionally required evaporation of the remnants of acid or
      oxidants was avoided because no significant interferences from these substances
      were observed, and thus analyte loss and potential contamination were minimized.
      A limit of detection of 0.005 ng mL(-1) for total mercury or inorganic mercury
      was obtained. A precision of less than 3% (RSD) at 2 MUg L(-1) of mercury species
      was typical. The accuracy of the method was validated by determination of mercury
      in geological and biological certified reference materials. The speciation
      analysis of Hg(2+) and MeHg was achieved by controlling the conditions of
      microwave-enhanced cold vapor generation and validated via determination of
      Certified Reference Materials DORM-2, DORM-3 and a real river water sample.

PMID- 22608428
TI  - Determination of polycyclic aromatic hydrocarbons in water samples using online
      microextraction by packed sorbent coupled with gas chromatography-mass
      spectrometry.
AB  - A fully automated microextraction by packed sorbents (MEPS) coupled with large
      volume injection gas chromatography-mass spectrometry (GC-MS) has been developed
      for the determination of eight polycyclic aromatic hydrocarbons (PAHs) in
      environmental water samples. Naphthalene (Nap), pyrene (Pyr), anthracene,
      acenaphthylene, phenanthrene, fluoranthene (Flr), fluorene and acenaphthene were
      the PAHs studied. The performance of the microextraction-GC-MS protocol was
      compared with solid phase extraction (SPE) and GC-MS analysis. Under optimized
      experimental conditions, the methods were linear for all analytes in the
      following ranges: 0.05-2.0 MUg L(-1) (MEPS) and 0.25-10.0 MUg L(-1) (SPE). The
      correlation coefficients (R(2)) were in the range 0.9965-0.9997 (MEPS) and 0.9978
      0.9998 (SPE) for all the analytes. Limits of detection (LODs) for 2 mL samples
      (MEPS) ranged from 0.8 ng L(-1) to 8.2 ng L(-1). LODs for 50 mL samples (SPE)
      were between 4.8 ng L(-1) and 35.9 ng L(-1). The two methods were successfully
      applied to the determination of the 8 PAHs in environmental waters, with
      recoveries in the range of 70-117% (MEPS) and 72-134% (SPE) for a real spiked
      sample. The two sample preparation processes showed good repeatabilities with
      intra-day relative standard deviations below 14.0% (MEPS) and 14.6% (SPE). Nap,
      Flr and Pyr were found in a river water sample.

PMID- 22608429
TI  - An improved methodology for data analysis in accelerated stability studies of
      peptide drugs: practical considerations.
AB  - Although the basic science behind current methods for studying biopharmaceutical
      drug stability has not changed significantly, the techniques available for
      predicting stability have evolved over the years. This paper therefore describes
      and discusses various options of data analysis for accelerated degradation
      studies of peptide and protein drugs based on the Arrhenius equation. Both linear
      and non-linear regression analyses are also discussed. The results indicate that
      the simultaneous treatment of all data, as opposed to determining individual rate
      constants is clearly preferable, combined with the use of the reparameterized
      Arrhenius equation. The estimated shelf-life at 5  degrees C varied between 2.2
      and 4.0 years in function of the temperature range and procedure used, whereas
      the precision of the estimated parameter is reflected in the width of the 95%
      confidence intervals, the classic Arrhenius analysis was maxima. All these
      results were evaluated by the bootstrap approach.

PMID- 22608430
TI  - Preconcentration and speciation of ultra-trace Se (IV) and Se (VI) in
      environmental water samples with nano-sized TiO2 colloid and determination by HG
      AFS.
AB  - A united method for speciation analysis of Se (IV) and Se (VI) in environmental
      water samples was developed using nano-sized TiO(2) colloid as adsorbent and
      hydride generation atomic fluorescence spectrometry (HG-AFS) as determination
      means. When the pH values of bulk solution were between 6.0 and 7.0, successful
      adsorption onto 1 mL nano-sized TiO(2) colloid (0.2%) was achieved for more than
      97.0% of Se (IV) while Se (VI) barely got adsorbed. Therefore, the method made it
      possible to preconcentrate and determine Se (IV) and Se (VI) separately. The
      precipitated TiO(2) with concentrated selenium was directly converted to colloid
      without desorption. Selenium in the resulting colloid was then determined by HG
      AFS. The detection limits (3sigma) and relative standard deviations (R.S.D) of
      this method were 24 ng/L and 42 ng/L, 7.8% (n=6) and 7.0% (n=6) for Se (IV) and
      Se (VI), respectively. This simple, sensitive, and united method was successfully
      applied to the separation and speciation of ultra-trace Se (IV) and Se (VI) in
      environmental water samples.

PMID- 22608431
TI  - Colorimetric and fluorescence sensing of Cu2+ in water using 1,8
      dihydroxyanthraquinone-beta-cyclodextrin complex with the assistance of ammonia.
AB  - 1,8-Dihydroxyanthraquinone (DHAQ) can form an inclusion complex with beta
      cyclodextrin(beta-CD) in aqueous media, which can be employed to solubilize and
      stabilize the DHAQ in water. With the assistance of ammonia, the supramolecular
      DHAQ-beta-CD complex showed a selective chromogenic behavior toward Cu(2+) ions
      by changing the color of the solution from citrus red to purple red, which could
      be easily observed with the naked eye. Moreover, fluorescence emission of the
      system was selectively quenched by Cu(2+) ions. The fluorescence response was
      concentration-dependent and can be well described by the typical Stern-Volmer
      model. An easily applied method for Cu(2+) determination in an aqueous medium was
      thus established. Under the optimum conditions, the method exhibits a dynamic
      response range for Cu(2+) from 8.0*10(-7) to 2.0*10(-5) M, with a detection limit
      of 2.7*10(-7) mol L(-1).

PMID- 22608432
TI  - A highly sensitive electrochemical assay for silver ion detection based on un
      labeled C-rich ssDNA probe and controlled assembly of MWCNTs.
AB  - We report here a highly sensitive electrochemical sensing platform for Ag(+)
      detection based on Ag(+)-induced conformational change of cytosine-rich single
      stranded DNA C-rich ssDNA probe and the controlled assembly of MWCNTs. In the
      protocol, the gold electrode was first modified with a dense 16
      mercaptohexadecanoic acid self-assembled monolayer (MHA/SAM). The hydrophobic
      MHA/SAM isolated the electrode from the electroactive indicator in the aqueous
      solution, which resulted in the electronic transmission blocking. It was eT OFF
      state. In the presence of Ag(+), C-Ag(+)-C coordination induced the
      conformational change of C-rich ssDNA probe from random-coil structure to fold
      into a hairpin structure, which cannot wrap on the surface of the MWCNTs. Then
      the "naked" MWCNTs can be assembled on the MHA/SAM gold electrode, mediating the
      electron transfer between the electrode and the electroactive indicator. It
      generated measurable electrochemical signals (eT ON). The resulting change in
      electron transfer efficiency was readily measured by differential pulse
      voltammetry at target Ag(+) concentrations as low as 1.3 nM. The linear response
      range for Ag(+) detection was from 10 to 500 nM. This method dose not need of
      electroactive molecules labeling on the C-rich ssDNA probe. Moreover, it has good
      selectivity to other environmentally relevant metal ions. Therefore, the
      developed electrochemical assay is an ideal method for Ag(+) detection with some
      advantages including sensitivity, selectivity, simplicity, low-cost, and no
      requirement for probe label preparation. We expect that this strategy could be a
      generalized platform for DNA-based sensing.

PMID- 22608433
TI  - Halogen-free ionic liquid as an additive in zinc(II)-selective electrode: surface
      analyses as correlated to the membrane activity.
AB  - Two conventional Zn(II) polyvinyl chloride (PVC) membrane electrodes have been
      prepared and characterized. They were based on dibenzo-24-crown-8 (DBC) as a
      neutral carrier, dioctyl phthalate (DOP) as a plasticizer, and potassium tetrakis
      (p-chlorophenyl) borate, KTpClPB or the halogen-free ionic liquid,
      tetraoctylammonium dodecylbenzene sulfonate [TOA][DBS] as an additive. The use of
      ionic liquid has been found to enhance the selectivity of the sensor. For each
      electrode, the surfaces of two membranes were investigated using X-ray
      photoelectron, ion-scattering spectroscopy and atomic force microscopy. One of
      the two membranes was conditioned by soaking it for 24 h in a 1.0*10(-3) M
      Zn(NO(3))(2) solution and the second was soaked in bi-distilled water for the
      same interval (24 h). Comparing the two surfaces indicated the following: (a) the
      high selectivity in case of using [TOA][DBS] as an additive is due to the extra
      mediation caused by the ionic liquid and (b) the working mechanism of the
      electrode is based on phase equilibrium at the surface of the membrane associated
      with ion transport through the bulk of the membrane.

PMID- 22608434
TI  - Electrochemistry and electrocatalysis of myoglobin intercalated in Mg2Al-Cl
      layered double hydroxide and ionic liquid composite material.
AB  - A novel biocompatible nanocomposite prepared by Mg(2)Al-Cl layered double
      hydroxide (LDH) and ionic liquid (IL) 1-carboxyl-methyl-3-methylimidazolium
      tetrafluoroborate was used as the matrix for the immobilization of myoglobin
      (Mb). The IL-LDH-Mb composite was characterized by UV-vis adsorption spectroscopy
      and the results indicated that Mb retained its native structure in the IL-LDH
      nanocomposite. The IL-LDH-Mb bionanocomposite was modified on the surface of
      carbon ionic liquid electrode to get an Mb modified electrode. Electrochemical
      experiments showed that direct electrochemistry of Mb in the composite was
      realized with a pair of well-defined redox peaks appeared, which could be
      attributed to the specific microenvironment provided by layer structured LDH and
      high ionic conductive IL present for Mb molecule. The modified electrode
      exhibited good direct electrocatalytic ability to the reduction of
      trichloroacetic acid and hydrogen peroxide with good stability and
      reproducibility. Different kinds of real samples were detected by the modified
      electrode with satisfactory results. So the IL-LDH nanocomposite provided a novel
      and efficient platform for the immobilization of enzymes, which had potential
      applications in the fabrication of third-generation biosensors.

PMID- 22608435
TI  - Determination of monensin in milk samples by front-surface long-wavelength
      fluoroimmunoassay using nile blue-doped silica nanoparticles as labels.
AB  - A heterogeneous immunoassay for monensin determination in milk samples using a
      tracer formed by anti-monensin antibodies bound to nile blue (NB)-doped silica
      nanoparticles (NPs), 96-well microplates as solid supports and long-wavelength
      fluorescence measurements is described for the first time. The assay relies on
      the competition of the monensin present in the samples with a monensin-bovine
      serum albumin conjugate, which was immobilized onto the well surface, for the
      active sites of anti-monensin antibodies. After subsequent incubation and washing
      steps, the fluorescence of the bound tracer fraction is measured onto the dry
      surface of the well. An antigen capture format was also assayed by immobilizing
      anti-sheep IgG previously to the incubation of sheep anti-monensin antibodies and
      using a tracer formed by monensin bound to nile blue-doped silica NPs, which
      competes with the analyte for binding the immobilized antibody. Although the
      fluorescence signal obtained in both formats can be correlated to the analyte
      concentration, better results were obtained using the antibody capture format.
      After the optimization of the system using this format, the method features a
      detection limit of 0.015 MUg L(-1) and a dynamic range from 0.05 to 5 MUg L(-1).
      The precision, assayed at two different analyte concentrations, 0.2 and 1 MUg L(
      1), and expressed as relative standard deviation, gave values of 5.9% and 4.0%,
      respectively. The method was satisfactorily applied to the analysis of milk
      samples, which only required a simple extraction step in order to remove the
      proteins from samples, giving recoveries in the range 83.3-107.5%.

PMID- 22608436
TI  - A nano-structured material for reliable speciation of chromium and manganese in
      drinking waters, surface waters and industrial wastewater effluents.
AB  - A simple solid phase extraction system based on the applying the nickel-aluminum
      layered double hydroxide (Ni-Al LDH) as a nano-sorbent was developed for the
      speciation analysis of chromium and manganese by flame atomic absorption
      spectrometry (FAAS). The method is based on the fact that Cr(VI) and Mn(VII)
      oxyanions could be adsorbed on the Ni-Al(NO(3)(-)) LDH and/or exchanged with LDH
      interlayer NO(3)(-) ions at pH 6.0, whereas Cr(III) and Mn(II) cations pass
      through the LDH-packed column without retention. The determinations of total Cr
      and Mn, and hence indirectly Cr(III) and Mn(II), involve the pre-oxidations of
      Cr(III) and Mn(II) to Cr(VI) and Mn(VII) with H(2)O(2) and acidic solution of
      KIO(4), respectively. Several important factors affecting the retention
      efficiency were investigated and optimized. In the optimum experimental
      conditions, the limits of detection (3S(b)/m) for Cr(VI) and Mn(VII) were 0.51
      and 0.47 ng mL(-1), and the relative standard deviations were 2.5 and 3.2%
      (C=30.0 ng mL(-1), n=6), respectively. The presented method was validated by the
      analysis of a certified reference material, and applied to the speciation of Cr
      and Mn in drinking waters, surface waters and industrial wastewater effluents.

PMID- 22608437
TI  - Evaluation of different extraction procedures for salivary peptide analysis.
AB  - Sample preparation is a critical step for all kind of biological fluids analysis
      with serious implications in data retrieved. In this sense, efforts have been
      made to standardize biofluids' management procedures for diagnosis and research
      purposes. However, no agreement exists regarding saliva preparation. Aiming the
      delineation of an ideal preparation procedure for salivary peptidome analysis,
      the commonly used extraction methods such as selective precipitation with organic
      solvents, acid and addition of chaotropic agents in combination with filtration,
      were evaluated in the present study. Data concerning protein/peptide content,
      Tricine-gel electrophoresis and MALDI-TOF/TOF identification suggest that
      centrifugation, a generally used sample cleanup step, should be critically
      reconsidered based on the hydrophobic peptides that can be loss by aggregation
      with high molecular weight (MW) components. Although no individual method per se
      resulted in the identification of all MS identified peptides, the extraction
      method with bicarbonate/acetonitrile (ACN) followed by filtration resulted in the
      higher number of identified peptides.

PMID- 22608438
TI  - A simple and reusable fluorescent sensor for heme proteins based on a conjugated
      polymer-doped electrospun nanofibrous membrane.
AB  - We reported a simple and reusable fluorescent sensor for heme proteins based on
      the electrospun nanofibrous membrane doped with a fluorescent conjugated polymer
      P. The sensor showed favorable fluorescence sensing performance towards the heme
      proteins, including hemoglobin (Hb), myoglobin (Mb) and cytochrome c (Cyt c). The
      surface wettability and sensing performance of the electrospun nanofibrous
      membrane were investigated in detail using Hb as the model. The nanofibrous
      sensor showed satisfactory reversibility with less than 10% signal loss after
      nine quenching-regeneration cycles, and good batch-to-batch reproducibility with
      a relative standard deviation of 3.4% (n=3). The linear range of the sensor for
      Hb determination was 2.0*10(-8) to 3.0*10(-6) M with a detection limit of 1.2*10(
      8) M. The quenching process is mainly based on the fluorescence resonance energy
      transfer mechanism between the fluorescent conjugated polymer P and the heme
      prosthetic groups, therefore the sensor was selective against most of the common
      interferents. As an example to evaluate the feasibility of the sensor in
      practical application, Hb in human blood samples was determined and the results
      were in good agreement with the data provided by the hospital. To the best of our
      knowledge, this is the first work using fluorescent electrospun nanofibrous
      sensor for protein analysis in real biological sample.

PMID- 22608439
TI  - Optimization of horseradish peroxidase-catalyzed enhanced chemiluminescence
      reaction by full factorial design.
AB  - Using a full factorial design the optimization of experimental conditions of
      enhanced chemiluminescence reaction (ECR) catalyzed by horseradish peroxidase
      (HRP-C) in the presence of 3-(10'-phenothiazinyl)propane-1-sulfonate (SPTZ) and 4
      morpholinopyridine (MORP) as enhancers was performed. The effect of
      concentrations of SPTZ, hydrogen peroxide, MORP, luminol, and Tris on a ratio of
      peroxidase-catalyzed CL to background was studied. The use of the full 2(5)
      factorial design instead of "one-variable-a time" method allowed to increase the
      sensitivity of HRP-C determination 2355 fold without a change of detection limit.
      The obtained results open up very promising perspectives for using HRP-C
      catalyzed ECR to improve the sensitivity of chemiluminescent enzyme immunoassay.

PMID- 22608440
TI  - Development of an automated on-line electrochemical chlorite ion sensor.
AB  - A sensor system for the automatic, in-line, determination of chlorite ion is
      reported. Electroanalytical measurements were performed in electrolyte-free
      liquids by using an electrochemical probe (EC), which enables in-line detection
      in high-resistance media such as disinfected water. Cyclic voltammetry scan rate
      studies suggest that the current arising from the oxidation of chlorite ion at an
      EC probe is mass-transfer limited. By coupling FIA with an EC probe amperometric
      cell, automated analysis was achieved. This sensor is intended to fulfill the
      daily monitoring requirements of the EPA DBP regulations for chlorite ion.
      Detection limits of 0.02-0.13 mg/L were attained, which is about one order of
      magnitude below the MRDL. The sensor showed no faradaic signal for perchlorate,
      chlorate, or nitrate. The lifetime and stability of the sensor were investigated
      by measuring calibration curves over time under constant-flow conditions.
      Detection limits of <0.1 mg/L were repeatedly achieved over a period of three
      weeks.

PMID- 22608442
TI  - Protein-templated gold nanoclusters based sensor for off-on detection of
      ciprofloxacin with a high selectivity.
AB  - In this contribution, bovine serum albumin stabilized gold nanoclusters as novel
      fluorescent probes were successfully utilized for the detection of ciprofloxacin
      for the first time. Our prepared gold nanoclusters exhibited strong emission with
      peak maximum at 635 nm. Cu(2+) was employed to quench the strong fluorescence of
      the gold nanoclusters, whereas the addition of ciprofloxacin caused the
      fluorescence intensity restoration of the Cu(2+)-gold nanoclusters system. The
      increase in fluorescence intensity of Cu(2+)-gold nanoclusters system caused by
      ciprofloxacin allows the sensitive detection of ciprofloxacin in the range of 0.4
      ng mL(-1) to 50 ng mL(-1). The detection limit for ciprofloxacin is 0.3 ng mL(-1)
      at a signal-to-noise ratio of 3. The present sensor for ciprofloxacin detection
      possesses a low detection limit and wide linear range. In addition, the real
      samples were analyzed with satisfactory results.

PMID- 22608441
TI  - Simultaneous determination of caffeic acid phenethyl ester and its metabolite
      caffeic acid in dog plasma using liquid chromatography tandem mass spectrometry.
AB  - A simple, reliable and sensitive method for the simultaneous determination of
      caffeic acid phenethyl ester (CAPE) and its metabolite caffeic acid (CA) in dog
      plasma was developed using liquid chromatography tandem mass spectrometry (LC
      MS/MS). The sample pretreatment generally involved protein precipitation
      treatment (PPT) and direct dilution. CAPE and CA were separated with a C18
      reversed-phase column. Electrospray ionization (ESI) interface operated in
      negative mode was chosen for ionization. Multiple reaction monitoring (MRM) mode
      was selected for data acquisition. The quantification range was 10.0-10,000.0 ng
      mL(-1). The intra- and inter-batch accuracies were within 92.5-107.0% with
      relative standard deviation (RSD, %) no more than 10.5%. CAPE and CA were proved
      to be stable in stabilizer-treated dog blood and PPT-treated plasma during the
      sampling and pretreatment period. The applicability has been evaluated with real
      samples from treated dogs.

PMID- 22608443
TI  - Method development for the determination of fluorine in toothpaste via molecular
      absorption of aluminum mono fluoride using a high-resolution continuum source
      nitrous oxide/acetylene flame atomic absorption spectrophotometer.
AB  - Fluorine was determined via the rotational molecular absorption line of aluminum
      mono fluoride (AlF) generated in C(2)H(2)/N(2)O flame at 227.4613 nm using a high
      resolution continuum source flame atomic absorption spectrophotometer (HR-CS
      FAAS). The effects of AlF wavelength, burner height, fuel rate (C(2)H(2)/N(2)O)
      and amount of Al on the accuracy, precision and sensitivity were investigated and
      optimized. The Al-F absorption band at 227.4613 nm was found to be the most
      suitable analytical line with respect to sensitivity and spectral interferences.
      Maximum sensitivity and a good linearity were obtained in acetylene-nitrous oxide
      flame at a flow rate of 210 L h(-1) and a burner height of 8mm using 3000 mg L(
      1) of Al for 10-1000 mg L(-1)of F. The accuracy and precision of the method were
      tested by analyzing spiked samples and waste water certified reference material.
      The results were in good agreement with the certified and spiked amounts as well
      as the precision of several days during this study was satisfactory (RSD<10%).
      The limit of detection and characteristic concentration of the method were 5.5 mg
      L(-1) and 72.8 mg L(-1), respectively. Finally, the fluorine concentrations in
      several toothpaste samples were determined. The results found and given by the
      producers were not significantly different. The method was simple, fast, accurate
      and sensitive.

PMID- 22608444
TI  - Zincon-immobilized silica-coated magnetic Fe3O4 nanoparticles for solid-phase
      extraction and determination of trace lead in natural and drinking waters by
      graphite furnace atomic absorption spectrometry.
AB  - A new protocol using zincon-immobilized silica-coated magnetic Fe(3)O(4)
      nanoparticles (Zincon-Si-MNPs) as solid-phase extraction (SPE) medium has been
      developed for the separation and preconcentration of trace lead in water. Various
      parameters such as pH, extraction time, concentration and volume of eluent,
      sample volume, and influence of co-existing ions have been investigated in order
      to establish the optimum conditions for the determination of lead in combination
      with graphite furnace atomic absorption spectrometry (GFAAS). The detection limit
      (LOD) of the proposed method for lead based on an enrichment factor of 200 was 10
      ng L(-1). The relative standard deviations (RSDs, n=5) were 8.3%, 7.8% and 9.2%,
      respectively, at 5, 0.5 and 0.05 ng mL(-1) levels. This method has been
      successfully applied to the analysis of trace lead in natural and drinking water
      samples and the recoveries for the spiked samples were in the range of 84-104%.

PMID- 22608445
TI  - A near-infrared-emitting CdTe/CdS core/shell quantum dots-based OFF-ON
      fluorescence sensor for highly selective and sensitive detection of Cd2+.
AB  - A near-infrared-emitting CdTe/CdS core/shell quantum dots (QDs)-based
      photoluminescence (PL) sensor was designed and applied for highly selective and
      sensitive detection of Cd(2+). This sensor was based on a PL "OFF-ON" mode.
      First, the addition of ammonium pyrrolidine dithiocarbamate (APDC) led to
      remarked PL quenching of QDs. Second, PL of APDC surface modified QDs (QDs-APDC)
      was gradually restored with the each increment of Cd(2+) concentration.
      Experimental results showed that PL of QDs-APDC was near proportional upon the
      addition of Cd(2+) in the range from 0.1 to 2 MUM with a good correlation
      coefficient of 0.9989. The limit of detection of this proposed method was 6 nM.
      Interferential experiments confirmed that this sensor of Cd(2+) was highly
      selective over other metal ions. To further investigate perfect analysis
      performance, this sensor was favorably utilized to determine Cd(2+) in tap water,
      river water and liposome solutions.

PMID- 22608446
TI  - Highly-sensitive cholesterol biosensor based on platinum-gold hybrid
      functionalized ZnO nanorods.
AB  - A novel scheme for the fabrication of gold/platinum hybrid functionalized ZnO
      nanorods (Pt-Au@ZnONRs) and multiwalled carbon nanotubes (MWCNTs) modified
      electrode is presented and its application for cholesterol biosensor is
      investigated. Firstly, Pt-Au@ZnONRs was prepared by the method of chemical
      synthesis. Then, the Pt-Au@ZnONRs suspension was dropped on the MWCNTs modified
      glass carbon electrode, and followed with cholesterol oxidase (ChOx)
      immobilization by the adsorbing interaction between the nano-material and ChOx as
      well as the electrostatic interaction between ZnONRs and ChOx molecules. The
      combination of MWCNTs and Pt-Au@ZnONRs provided a favorable environment for ChOx
      and resulted in the enhanced analytical response of the biosensor. The resulted
      biosensor exhibited a linear response to cholesterol in the wide range of 0.1
      759.3 MUM with a low detection limit of 0.03 MUM and a high sensitivity of 26.8
      MUA mM(-1). The calculated apparent Michaelis constant K(M)(app) was 1.84 mM,
      indicating a high affinity between ChOx and cholesterol.

PMID- 22608447
TI  - A rapid and sensitive colorimetric assay method for Co2+ based on the modified Au
      nanoparticles (NPs): understanding the involved interactions from experiments and
      simulations.
AB  - We previously reported a colorimetric assay method for Co(2+) based on the
      thioglycolic acid (TGA) functionalized hexadecyl trimethyl ammonium bromide
      (CTAB) modified Au NPs. However, the detection limit of 3*10(-7) M was still
      higher than that of the sanitary standard for drinking water (6.8*10(-8) M). In
      addition, the interactions between the modifier and Au NPs, and between the
      modifier-Au NPs and Co(2+) remain to be clarified and confirmed. Thus, in the
      present study, the modified Au NPs solution was dialyzed and its detection limit
      was optimized to be 5*10(-10) M. The interactions between the modifier and Au
      NPs, and between the modifier-Au NPs and Co(2+) were investigated in both
      experimental characterizations and theoretical calculations, consistently
      confirming that the Au NPs were modified by the negatively charged anions of
      [SCH(2)CO(2)](2-) through Au-S bonds and Co(2+) was recognized by the modifier-Au
      NPs through Co-O chelate bonds. The results of X-ray photoelectron spectroscopy
      (XPS) suggest that there were no chemical bonds formed between CTAB and Co(2+).
      Moreover, the colorimetric assay of Co(2+) using the modified Au NPs has been
      proved to be a rapid, very sensitive and highly selective method. The validation
      of the method was carried out by analysis of a certified reference material, GSBZ
      50030-94.

PMID- 22608448
TI  - Light-induced pH change and its application to solid phase extraction of trace
      heavy metals by high-magnetization Fe3O4@SiO2@TiO2 nanoparticles followed by
      inductively coupled plasma mass spectrometry detection.
AB  - We report here the preparation of high-magnetization Fe(3)O(4)@SiO(2)@TiO(2)
      nanoparticles for solid phase extraction of trace amounts of Cd(II), Cr(III),
      Mn(II) and Cu(II) from environmental waters. The prepared nanoparticles were
      characterized by scanning electron micrograph (SEM) and transmission electron
      microscopy (TEM). The high-magnetization nanoparticles carrying the target metals
      could be easily and fast separated from the aqueous solution simply by applying
      an external magnetic field while no filtration or centrifugation was necessary. A
      light-induced hydroxide ion emitter, molecular malachite green carbinol base
      (MGCB) was applied to adjust pH value of solution for quantitative adsorption
      instead of the conventional used buffer. In the presence of UV light, MGCB gives
      out OH(-) ions, and this leads to an increase in the pH value without the aid of
      buffer solution. Using high-magnetization Fe(3)O(4)@SiO(2)@TiO(2) nanoparticles
      as the extraction material and the light-induced MGCB for pH adjustment, we
      developed an efficient and convenient two-step method for
      separation/preconcentration trace amounts of Cd(II), Cr(III), Mn(II) and Cu(II)
      in environmental water samples followed by inductively coupled plasma mass
      spectrometry (ICP-MS) detection. The parameters affecting the extraction such as
      MGCB concentration, exposal time, sample volume, eluent condition, and
      interfering ions have been investigated in detail. Under the optimized
      conditions, the limits of detection for Cd(II), Cr(III), Mn(II) and Cu(II) were
      4.0, 2.6, 1.6 and 2.3 ng L(-1), respectively, and the relative standard
      deviations (RSDs, c=1 MUg L(-1), n=7) were 3.6%, 4.5%, 4.0 and 4.1%,
      respectively. The proposed method has been validated using certified reference
      materials, and it has been successfully applied in the determination of trace
      Cd(II), Cr(III), Mn(II) and Cu(II) in environmental water samples.

PMID- 22608449
TI  - Spirally oriented Au microelectrode array sensor for detection of Hg (II).
AB  - A simple and reproducible carbon microelectrode array (CMA), designed to
      eliminate diffusive interference among the microelectrodes, has been fabricated
      and used as a frame to build a gold (Au) microelectrode array (GMA) sensor. To
      prepare the CMA initially, rather than use an uncontrollable large number of
      carbon fibers, only 60 carbon fibers of regular size were used to ensure
      manageable and reproducible arrangement for array construction. In addition, for
      efficient spatial arrangement of the microelectrode and easy sensor preparation,
      carbon fibers were oriented in a spiral fashion by rolling around a Cu wire. The
      distance between carbon fibers was carefully determined to avoid overlap among
      individual diffusion layers, one of the important factors governing steady-state
      current response and sensor-to-sensor reproducibility. After the preparation of a
      spirally arranged CMA, Au was electrochemically deposited on the surface of
      individual carbon electrodes to build a final GMA sensor. Then, the GMA sensor
      was used to measure Hg(2+) in a low concentration range. Simultaneously, multiple
      GMA sensors were independently prepared to examine reproducibility in sensor
      fabrication as well as electrochemical measurement (sensor-to-sensor
      reproducibility). Overall, highly sensitive detection of Hg(2+) was possible
      using the proposed GMA sensor due to efficient arrangement of microelectrodes and
      the sensor-to-sensor reproducibility was superior owing to simplicity in sensor
      fabrication.

PMID- 22608450
TI  - Microemulsion-enhanced electrochemiluminescence of luminol-H2O2 for sensitive
      flow injection analysis of antioxidant compounds.
AB  - A microemulsion enhanced electrochemiluminescence (ECL) of luminol-H(2)O(2) was
      studied with the flow-injection (FI) technique. The results revealed that the
      microemulsion composed with cetyltrimethylammonium bromide (CTAB), n-butanol, n
      heptane and water greatly enhanced the ECL especially in acidic medium. The ECL
      emission increased for 20 to 2 times in this microemulsion medium over the pH
      range of 5.0-8.0 compared to that in aqueous solution. The mechanism of
      enhancement of surfactant and microemulsion for luminol-H(2)O(2) ECL was
      discussed. It is mainly based on the electrostatic interaction between luminol
      anion and the head group of surfactant, which causes the adsorption and promotes
      the dissociation of luminol on the surfaces of the microemulsion droplets, favors
      the oxidation of luminol by the yielded reactive oxygen species (ROSs) during
      electrolysis. This research is very significant for ECL applications because of
      the extended practicable pH range which was suitable for environmental and
      biological systems. As an example, this FI-ECL technique can be applied for
      determination of oligo proanthocyanidin (OPC) because of its antioxidant property
      and to evaluate the total antioxidant activity of the grape skin using OPC as an
      index.

PMID- 22608451
TI  - Rhodamine 6G conjugated-quantum dots used for highly sensitive and selective
      ratiometric fluorescence sensor of glutathione.
AB  - Rhodamine 6G (R6G) and 3-mercaptopropionic acid (MPA) capped-CdTe quantum dots
      (QDs) were conjugated by electrostatic interactions in aqueous solution. The R6G
      QDs conjugate was utilized as a photoluminescence (PL) ratiometric sensor for the
      detection of glutathione (GSH). In this method, intentional introduction of GSH
      destroyed the conjugation of R6G and QDs, and induced regular PL change of R6G
      QDs conjugates due to the competitive chelation between GSH and MPA ligand on the
      surface of QDs. The ratio of PL intensity of R6G (I(R6G)) to that of QDs (I(QDs))
      in this conjugate was near linear toward the concentration of GSH in the range
      from 0.05 to 80 MUM, and corresponding regression equation showed a good linear
      coefficient of 0.9954. The limit of detection of 15 nM in this proposed method
      was about 40-fold lower than that of other QDs-based PL sensors. Interferential
      experiments testified that R6G-QDs conjugates-based ratiometric PL sensor of GSH
      showed high selectivity over other related thiols and amino acids. Real sample
      assays further verified perfect analysis performance of the PL sensor of GSH. In
      comparison with conventional analytical techniques for the measurement of GSH,
      this ratiometric PL sensor was facile, economic, highly sensitive and selective.

PMID- 22608452
TI  - An improved ensemble partial least squares for analysis of near-infrared spectra.
AB  - Traditional ensemble regression algorithms such as BAgging Partial Least Squares
      (BAPLS) and BOosting Partial Least Squares (BOPLS) do not perform very well in
      the data set that is relatively small or contaminated by random noise. To make
      the method robust and improve its prediction ability, inspired from bias-variance
      covariance decomposition, we propose an improved ensemble partial least squares
      method based on the diversity. The new method is applied to quantitative analysis
      of Near InfraRed (NIR) data sets. A comparative study between the proposed method
      and other previous methods including BAPLS and BOPLS on two NIR data sets is
      provided. Experimental results show that the proposed method can achieve better
      performance than other methods.

PMID- 22608453
TI  - Focused microwave-induced combustion for digestion of botanical samples and
      metals determination by ICP OES and ICP-MS.
AB  - The advantages and shortcomings of focused microwave-induced combustion (FMIC)
      for digestion of plant samples were studied. The effects of sample mass,
      absorbing solution, oxygen gas flow-rate, and time of reflux step on recoveries
      of major, minor and trace metals were systematically evaluated. Afterwards, Al,
      Ba, Ca, Co, Cr, Cu, Mg, Mn, Ni, Sr, V, and Zn were determined by inductively
      coupled plasma optical emission spectrometry (ICP OES) and by inductively coupled
      plasma mass spectrometry (ICP-MS). The main advantages of FMIC when compared to
      microwave-assisted wet digestion (MAWD) and focused-microwave-assisted wet
      digestion (FMAWD) are the possibility to digest larger masses of samples (up to
      3g) using shorter heating times and diluted nitric acid solution for absorbing
      all analytes. Using the selected experimental conditions for FMIC, residual
      carbon content was lower than 0.7% for all samples and relative standard
      deviation (RSD) varied from 1.5 to 14.1%. Certified reference materials (NIST
      1515 apple leaves and NIST 1547 peach leaves) were used for checking accuracy and
      determined values for all metals were in agreement with certified values at a 95%
      confidence level. No statistical difference (ANOVA, 95% of confidence level) was
      observed for results obtained by FMIC, FMAWD, and MAWD. Limits of detection were
      lower when using FMIC in the range of 0.02-0.15 MUg g(-1) for ICP OES and 0.001
      0.01 MUg g(-1) for ICP-MS, which were about 3 and 6 times lower than the values
      obtained by FMAWD and MAWD, respectively. It is important to point out that FMIC
      was a suitable sample preparation method for major, minor and trace metals by
      both determination techniques (ICP OES and ICP-MS). Additionally, since it allows
      lower LODs (because up to 3g of sample can be digested) and diluted acid
      solutions are used (without any further dilution), the use of ICP-MS is not
      mandatory.

PMID- 22608454
TI  - Electrochemical immunosensor for multiplexed detection of food-borne pathogens
      using nanocrystal bioconjugates and MWCNT screen-printed electrode.
AB  - Bacterial food poisoning is an ever-present threat that can be prevented with
      proper care and handling of food products. A disposable electrochemical
      immunosensor for the simultaneous measurements of common food pathogenic bacteria
      namely Escherichia coli O157:H7 (E. coli), campylobacter and salmonella were
      developed. The immunosensor was fabricated by immobilizing the mixture of anti-E.
      coli, anti-campylobacter and anti-salmonella antibodies with a ratio of 1:1:1 on
      the surface of the multiwall carbon nanotube-polyallylamine modified screen
      printed electrode (MWCNT-PAH/SPE). Bacteria suspension became attached to the
      immobilized antibodies when the immunosensor was incubated in liquid samples. The
      sandwich immunoassay was performed with three antibodies conjugated with specific
      nanocrystal (alpha-E. coli-CdS, alpha-campylobacter-PbS and alpha-salmonella-CuS)
      which has releasable metal ions for electrochemical measurements. The square wave
      anodic stripping voltammetry (SWASV) was employed to measure released metal ions
      from bound antibody nanocrystal conjugates. The calibration curves for three
      selected bacteria were found in the range of 1*10(3)-5*10(5) cells mL(-1) with
      the limit of detection (LOD) 400 cells mL(-1) for salmonella, 400 cells mL(-1)
      for campylobacter and 800 cells mL(-1) for E. coli. The precision and sensitivity
      of this method show the feasibility of multiplexed determination of bacteria in
      milk samples.

PMID- 22608455
TI  - Predicting feedstock and percent composition for blends of biodiesel with
      conventional diesel using chemometrics and gas chromatography-mass spectrometry.
AB  - The two main goals of the analytical method described herein were to (1) use
      principal component analysis (PCA), hierarchical clustering (HCA) and K-nearest
      neighbors (KNN) to determine the feedstock source of blends of biodiesel and
      conventional diesel (feedstocks were two sources of soy, two strains of jatropha,
      and a local feedstock) and (2) use a partial least squares (PLS) model built
      specifically for each feedstock to determine the percent composition of the
      blend. The chemometric models were built using training sets composed of total
      ion current chromatograms from gas chromatography-quadrupole mass spectrometry
      (GC-qMS) using a polar column. The models were used to semi-automatically
      determine feedstock and blend percent composition of independent test set
      samples. The PLS predictions for jatropha blends had RMSEC=0.6, RMSECV=1.2, and
      RMSEP=1.4. The PLS predictions for soy blends had RMSEC=0.5, RMSECV=0.8, and
      RMSEP=1.2. The average relative error in predicted test set sample compositions
      was 5% for jatropha blends and 4% for soy blends.

PMID- 22608456
TI  - Influence of macroporous gold support and its functionalization on lactate
      oxidase-based biosensors response.
AB  - A general bioanalytical platform for biosensor applications was developed based
      on three-dimensional ordered macroporous (3DOM) gold film modified electrodes
      using lactate oxidase (LOx) as a case study, within the framework of developing
      approaches of broad applicability. The electrode was electrochemically fabricated
      with an inverted opal template, making the surface area of the 3DOM gold
      electrode up to 18 times higher than that of bare flat gold electrodes. These new
      electrochemical transducers were characterized by using Field Emission Scanning
      Electron Microscopy (FE-SEM), Atomic Force Microscopy (AFM) and the X-ray
      diffraction (XRD). The biosensor was developed by immobilization of lactate
      oxidase (LOx), on a 3DOM gold electrode modified with a self-assembled monolayer
      of dithiobis-N-succinimidyl propionate (DTSP). The resulting lactate oxidase
      biosensor was characterized by electrochemical impedance spectroscopy (EIS). The
      3DOM gold electrode not only provides a good biocompatible microenvironment but
      also promotes the increase of conductivity and stability. Thus, the developed
      lactate oxidase bioanalytical platforms showed higher mediated
      bioelectrocatalytic activity compared to others previously described based on
      polycrystalline gold transducers. The response to varying lactate concentrations
      has been obtained in the presence of hydroxymethylferrocene as redox mediator in
      solution. Under these conditions, the bioanalytical platform response for DTSP
      covalently bound enzyme was improved with respect to that obtained in absence of
      DTSP.

PMID- 22608457
TI  - Spectrometric analysis of process etching solutions of the photovoltaic industry-
      determination of HNO3, HF, and H2SiF6 using high-resolution continuum source
      absorption spectrometry of diatomic molecules and atoms.
AB  - The surface of raw multicrystalline silicon wafers is treated with HF-HNO(3)
      mixtures in order to remove the saw damage and to obtain a well-like structured
      surface of low reflectivity, the so-called texture. The industrial production of
      solar cells requires a consistent level of texturization for tens of thousands of
      wafers. Therefore, knowing the actual composition of the etch bath is a key
      element in process control in order to maintain a certain etch rate through
      replenishment of the consumed acids. The present paper describes a novel approach
      to quantify nitric acid (HNO(3)), hydrofluoric acid (HF), and hexafluosilicic
      acid (H(2)SiF(6)) using a high-resolution continuum source graphite furnace
      absorption spectrometer. The concentrations of Si (via Si atom absorption at the
      wavelength 251.611 nm, m(0),(Si)=130 pg), of nitrate (via molecular absorption of
      NO at the wavelength 214.803 nm, [Formula: see text] ), and of total fluoride
      (via molecular absorption of AlF at the wavelength 227.46 nm, m(0,F)=13 pg) were
      measured against aqueous standard solutions. The concentrations of H(2)SiF(6) and
      HNO(3) are directly obtained from the measurements. The HF concentration is
      calculated from the difference between the total fluoride content, and the amount
      of fluoride bound as H(2)SiF(6). H(2)SiF(6) and HNO(3) can be determined with a
      relative uncertainty of less than 5% and recoveries of 97-103% and 96-105%,
      respectively. With regards to HF, acceptable results in terms of recovery and
      uncertainty are obtained for HF concentrations that are typical for the
      photovoltaic industry. The presented procedure has the unique advantage that the
      concentration of both, acids and metal impurities in etch solutions, can be
      routinely determined by a single analytical instrument.

PMID- 22608458
TI  - Deep Raman spectroscopy for the non-invasive standoff detection of concealed
      chemical threat agents.
AB  - Deep Raman spectroscopy has been utilized for the standoff detection of concealed
      chemical threat agents from a distance of 15 m under real life background
      illumination conditions. By using combined time and space resolved measurements,
      various explosive precursors hidden in opaque plastic containers were identified
      non-invasively. Our results confirm that combined time and space resolved Raman
      spectroscopy leads to higher selectivity towards the sub-layer over the surface
      layer as well as enhanced rejection of fluorescence from the container surface
      when compared to standoff spatially offset Raman spectroscopy. Raman spectra that
      have minimal interference from the packaging material and good signal-to-noise
      ratio were acquired within 5 s of measurement time. A new combined time and space
      resolved Raman spectrometer has been designed with nanosecond laser excitation
      and gated detection, making it of lower cost and complexity than picosecond-based
      laboratory systems.

PMID- 22608459
TI  - A new method for the identification and quantification of magnetite-maghemite
      mixture using conventional X-ray diffraction technique.
AB  - The electrical explosion of Fe wire in air produced nanoparticles containing the
      binary mixture of magnetite (Fe(3)O(4)) and maghemite (gamma-Fe(2)O(3)). The
      phase identification of magnetite and maghemite by the conventional X-ray
      diffraction method is not a simple matter because both have the same cubic
      structure and their lattice parameters are almost identical. Here, we propose a
      convenient method to assess the presence of magnetite-maghemite mixture and to
      further quantify its phase composition using the conventional peak deconvolution
      technique. A careful step scan around the high-angle peaks as (511) and (440)
      revealed the clear doublets indicative of the mixture phases. The quantitative
      analysis of the mixture phase was carried out by constructing a calibration curve
      using the pure magnetite and maghemite powders commercially available. The
      correlation coefficients, R(2), for magnetite-maghemite mixture was 0.9941.
      According to the method, the iron oxide nanoparticles prepared by the wire
      explosion in this study was calculated to contain 55.8 wt.% maghemite and 44.2
      wt.% magnetite. We believe that the proposed method would be a convenient tool
      for the study of the magnetite-maghemite mixture which otherwise requires highly
      sophisticated equipments and techniques.

PMID- 22608460
TI  - Contamination of ultrapure water with bisphenol A leached from polysulfone
      ultrafilter.
AB  - Ultrapure water produced by a water purification system is one of the most
      essential and widely used reagents in laboratories. However, its quality is
      usually the least well-characterized and often overlooked. Here we investigate
      the contamination of ultrapure water by bisphenol A (BPA) leached from a
      polysulfone (PS) ultrafilter in a water purification system. To evaluate the
      level of BPA in ultrapure water, we used an offline solid-phase extraction (SPE)
      coupled with liquid chromatography mass spectrometry (LC-MS). Initial BPA level
      leached from a new PS ultrafilter was 0.70+/-0.06 ng/mL. The concentration of BPA
      decreased gradually with continuous dispensation of purified water and was 0.20+/
      0.02 ng/mL at 33.5-L dispensation. The total amount of extractable BPA was 64.4+/
      1.4 MUg per PS ultrafilter. The cumulative amount of BPA leached during
      dispensation of 33.5-L water was 1.2+/-0.1 MUg, which only accounts for 2% of the
      total amount of extractable BPA.

PMID- 22608461
TI  - An electrochemiluminescence sensor based on a Ru(bpy)3(2+)-silica
      chitosan/nanogold composite film.
AB  - Chitosan, a cationic polysaccharide containing amino and hydroxyl groups, was
      used to fabricate an electrochemiluminescence (ECL) sensor. In the sensor
      construction, a glassy carbon electrode (GCE) was first coated by a chitosan film
      which embedded gold nanoparticles, and then the film was modified by introducing
      carboxyl groups on the surface, which were used to immobilize tris(2,2'
      bipyridyl)ruthenium(II) doped amino-functional silica nanoparticles (NH(2)
      RuSiNPs) through amido links. The successful modification was confirmed by
      scanning electronic microscopy and cyclic voltammetry. A binding model between
      the chitosan/nanogold composite film and NH(2)-RuSiNPs was also proposed, in
      which the amido link was the dominant bonding, accompanied with hydrogen bond
      interaction. ECL studies revealed that the sensor had very good response to
      different concentrations of 2-(dibutylamino) ethanol. This sensor was also
      applied in methamphetamine determination.

PMID- 22608462
TI  - Response to comments on "Uncertainty profiles for the validation of analytical
      methods".

PMID- 22608463
TI  - [Renal-appendicular fistula of the renal graft in a transplanted patient: an
      uncommon form of lower gastrointestinal haemorrhage].

PMID- 22608465
TI  - Pharmacologic management of coagulopathy in cardiac surgery: an update.

PMID- 22608464
TI  - Recent insights into pulmonary repair following virus-induced inflammation of the
      respiratory tract.
AB  - A hallmark of infection by respiratory viruses is productive infection of and the
      subsequent destruction of the airway epithelium. These viruses can also target
      other stromal cell types as well as in certain instances, CD45(+) hematopoietic
      cells either resident in the lungs or part of the inflammatory response to
      infection. The mechanisms by which the virus produces injury to these cell types
      include direct infection with cytopathic effects as a consequence of replication.
      Host mediated damage is also a culprit in pulmonary injury as both innate and
      adaptive immune cells produce soluble and cell-associated pro-inflammatory
      mediators. Recently, it has become increasingly clear that in addition to control
      of excess inflammation and virus elimination, the resolution of infection
      requires an active repair process, which is necessary to regain normal
      respiratory function and restore the lungs to homeostasis. The repair response
      must re-establish the epithelial barrier and regenerate the microarchitecture of
      the lung. Emerging areas of research have highlighted the importance of innate
      immune cells, particularly the newly described innate lymphoid cells, as well as
      alternatively activated macrophages and pulmonary stem cells in the repair
      process. The mechanisms by which respiratory viruses may impede or alter the
      repair response will be important areas of research for identifying therapeutic
      targets aimed at limiting virus and host mediated injury and expediting recovery.

PMID- 22608467
TI  - Variability in transfusion practice and effectiveness of strategies to improve
      it.

PMID- 22608466
TI  - Breakthroughs in anticoagulation: advent of the oral direct factor Xa inhibitors.
AB  - The oral direct factor Xa inhibitors include rivaroxaban and apixaban that
      recently have been evaluated comprehensively in multiple randomized clinical
      trials. Based on the efficacy and safety data from these trials, these novel
      anticoagulants are disseminating throughout clinical practice for
      thromboprophylaxis in major lower-extremity joint replacement, acute medical
      illness, atrial fibrillation, and acute coronary syndromes. The advantages of the
      xabans over vitamin K antagonists include no requirement for routine
      anticoagulation monitoring as well as a fast and reliable onset of action. The
      first perioperative limitation of the xabans is the lack of a routine coagulation
      test for monitoring their anticoagulant effect in scenarios, such as the timing
      of surgical procedures, the reversal of xaban-related bleeding, and the conduct
      of regional anesthesia. A second perioperative limitation is the lack of fully
      validated clinical reversal agents although prothrombin complex concentrate,
      recombinant factor VIIa, and factor X concentrate are options for xaban reversal
      in life-threatening bleeding scenarios. Given their clinical efficacy and
      advantages, further xabans are in clinical development, with edoxaban already in
      phase III clinical trials. Although the xabans have ushered in a new paradigm for
      clinical anticoagulation, further clinical trials are indicated to refine their
      clinical indications even further, such as anticoagulation for patients with
      mechanical heart valves.

PMID- 22608469
TI  - Dynamic mitral regurgitation without regional wall motion abnormality.

PMID- 22608470
TI  - How to manage aspirin resistance early after coronary artery bypass grafting.

PMID- 22608471
TI  - Single-walled carbon nanotube behavior in representative mature leachate.
AB  - Escalating production and subsequent incorporation of engineered nanomaterials in
      consumer products increases the likelihood of nanomaterials being discarded in
      landfills. Although direct measurement of particle disposal has not yet occurred,
      life cycle assessments suggest that over 50% of nanomaterials produced will
      eventually reside in landfills. Laboratory-scale experiments were conducted to
      evaluate how organics (humic acid: 20-800 mg/L), ionic strength (100-400 mM
      NaCl), and pH (6-8) typical of mature leachates influence carbon nanotube surface
      charge, relative stability, and mobility through representative solid waste
      environments. Results from the batch experiments suggest that the presence of
      high molecular weight organics, such as humic acid, acts to stabilize carbon
      nanotubes present in leachate, even at high ionic strengths (>100 mM NaCl). These
      results also suggest that in mature landfill leachate, as long as humic acid is
      present, ionic strength (when represented as NaCl) will be a dominant factor
      influencing nanomaterial stability. Column experiment results indicate the carbon
      nanotubes may be mobile through solid waste, suggesting particle placement within
      landfills needs to be examined more closely.

PMID- 22608472
TI  - Porcelain gallbladder and thalassaemia intermedia: association or coincidence?

PMID- 22608473
TI  - Peak-to-peak amplitude in neonatal brain monitoring of premature infants.
AB  - OBJECTIVE: To assess the strength of association between alternative measures of
      electroencephalographic (EEG) signal peak-to-peak amplitude (ppA) and
      postmenstrual age (PMA) among a cohort of extremely premature infants. METHODS:
      177 Two-channel EEG recordings 3-6h long were collected from 26 infants born
      before 29weeks of gestation. The raw EEG was converted into four different
      continuous measures of ppA: amplitude-integrated EEG (aEEG), range-EEG (rEEG),
      Gotman and Gloor's half-wave decomposition (HWD), and root of mean squares (RMS).
      For each ppA-measure EEG indices including mean, median, and 5% margins; indices
      of spread (width, standard deviation, coefficient of variation), and asymmetry
      were calculated for each 1min epoch. The medians of each index for the entire
      recording were tested for association with PMA using linear mixed models.
      RESULTS: The log-transformed values of aEEG and rEEG indices of spread were
      highly associated with PMA (fixed effects R(beta)(2)=0.84-0.89). CONCLUSIONS:
      Indices of spread by aEEG or rEEG can be used as indicators of neonatal brain
      maturation. However, rEEG produces the absolute values that most closely
      approximate the raw EEG amplitudes. SIGNIFICANCE: The indices of spread and rEEG
      as a measure of ppA provide a basis for improvements in neonatal EEG monitoring.

PMID- 22608474
TI  - The segmental palmar test in diagnosing carpal tunnel syndrome reassessed.
AB  - OBJECTIVE: To test our hypothesis that comparing the sensory nerve conduction
      velocity of the median nerve across the wrist with that of the forearm is more
      sensitive than comparing it with that of the palm in the electrodiagnostic
      confirmation of carpal tunnel syndrome (CTS). METHODS: One hundred and fifty
      seven consecutive patients with clinically defined CTS were prospectively
      included and electrophysiologically examined. Antidromic nerve conduction
      velocities were measured in 3 segments of the median nerve: forearm, wrist, and
      palm. Differences and ratios in nerve conduction velocities were computed between
      the forearm and wrist and between the palm and wrist segments. RESULTS: Comparing
      the median nerve conduction velocities of the forearm with the wrist segment
      provides a greater sensitivity (79.6% and 82.8% for the second and third digit,
      respectively) than comparing the palm with the wrist segment (65.6% and 65.0%).
      Applying the ratio leads to slightly higher sensitivities for both comparisons.
      CONCLUSIONS: The modified segmental palmar test is a sensitive, robust and easily
      applicable method in diagnosing CTS. SIGNIFICANCE: We recommend to use the median
      nerve sensory conduction velocity in the forearm as a reference in the segmental
      palmar test instead of that in the palm.

PMID- 22608475
TI  - Validity of multi-fiber muscle velocity recovery cycles recorded at a single site
      using submaximal stimuli.
AB  - OBJECTIVE: To examine the validity of multi-fiber muscle velocity recovery cycles
      (VRCs) recorded by direct muscle stimulation with submaximal stimuli. METHODS:
      VRCs were recorded from tibialis anterior muscle in normal volunteers with 1, 2
      and 5 conditioning stimuli. Recordings were made with 6 different amplitudes of
      conditioning stimuli. Recordings were also made with two recording electrodes, at
      least 15mm apart. RESULTS: Muscle VRCs in 6 subjects were not significantly
      different for conditioning stimuli between 80% and 150% of test stimulus
      amplitude. When recorded at two sites in 9 subjects, VRCs were similar when
      estimated over the shorter distance, the longer distance, and from the conduction
      time between the two electrodes. CONCLUSIONS: Multi-fiber muscle VRCs can be
      reliably recorded with a single recording electrode and with equal amplitude
      conditioning and test stimuli. SIGNIFICANCE: Clinical neurophysiologists can be
      assured that this new method of testing muscle membrane properties provides valid
      and robust measurements on normal muscles.

PMID- 22608476
TI  - Cellular changes of the corneal epithelium and stroma in herpes simplex
      keratitis: an in vivo confocal microscopy study.
AB  - PURPOSE: To analyze the morphologic features of corneal epithelial cells and
      keratocytes by in vivo confocal microscopy in patients with herpes simplex
      keratitis (HSK) as associated with corneal innervation. DESIGN: Prospective,
      cross-sectional, controlled, single-center study. PARTICIPANTS: Thirty-one eyes
      with the diagnosis HSK and their contralateral clinically unaffected eyes were
      studied and compared with normal controls (n = 15). METHODS: In vivo confocal
      microscopy (Confoscan 4; Nidek Technologies, Gamagori, Japan) and corneal
      esthesiometry (Cochet-Bonnet; Luneau Ophthalmologie, Chartres, France) of the
      central cornea were performed bilaterally in all patients and controls. Patients
      were grouped into normal (>5.5 cm), mild (>2.5-5.5 cm), and severe (<2.5 cm) loss
      of sensation. MAIN OUTCOME MEASURES: Changes in morphologic features and density
      of the superficial and basal epithelial cells, as well as stromal keratocytes,
      were assessed by 2 masked observers. Changes were correlated to corneal
      sensation, number of nerves, and total length of nerves. RESULTS: There was a
      significant and gradual decrease in the density of superficial epithelial cells
      in HSK eyes, with 852.50 +/- 24.4 cells/mm(2) in eyes with severe sensation loss
      and 2435.23 +/- 224.3 cells/mm(2) in control eyes (P = 0.008). Superficial
      epithelial cell size was 2.5-fold larger in HSK eyes (835.3 MUm(2)) compared with
      contralateral or normal eyes (407.4 MUm(2); P = 0.003). A significant number of
      hyperreflective desquamating superficial epithelial cells were present in HSK
      eyes with normal (6.4%), mild (29.1%), and severe (52.2%) loss of sensation, but
      were absent in controls. The density of basal epithelial cells, anterior
      keratocytes, and posterior keratocytes did not show statistical significance
      between patients and controls. Changes in superficial epithelial cell density and
      morphologic features correlated strongly with total nerve length, number, and
      corneal sensation. Scans of contralateral eyes did not show any significant
      epithelial or stromal changes compared with controls. CONCLUSIONS: In vivo
      confocal microscopy reveals profound HSK-induced changes in the superficial
      epithelium, as demonstrated by increase in cell size, decrease in cell density,
      and squamous metaplasia. This study demonstrated that these changes correlate
      strongly with changes in corneal innervation.

PMID- 22608477
TI  - Tuberous sclerosis complex: genotype/phenotype correlation of retinal findings.
AB  - OBJECTIVE: To evaluate genotype/phenotype correlations in individuals with
      astrocytic hamartoma (AH) and retinal achromic patch (AP) in the setting of
      tuberous sclerosis complex (TSC). DESIGN: Retrospective consecutive case series.
      PARTICIPANTS: A total of 132 patients enrolled in the Cleveland Clinic Foundation
      Tuberous Sclerosis Program (CCF-TSCP) and 907 patients from the Tuberous
      Sclerosis Alliance (TSC-A). METHODS: Patient gender, age at TSC diagnosis,
      presence of TSC1 or TSC2 mutations, detailed ophthalmic examination findings,
      systemic manifestations, and whether or not the patient had a diagnosis of
      epilepsy or cognitive impairment were analyzed. MAIN OUTCOME MEASURES:
      Genotype/phenotype correlation of retinal findings and systemic disease
      manifestations. RESULTS: No significant difference was found in the prevalence of
      AH or AP in the CCF-TSCP (36.1%) and TSC-A (34.1%) groups (P = 0.743). Astrocytic
      hamartomas were bilateral in 43.3% and 18.1% (P=0.009) and multiple in 40.0% and
      15.3% (P = 0.008) in the CCF-TSCP and TSC-A groups, respectively. In the CCF-TSCP
      group, the average number of AH was 4 (range, 2-7). Average tumor size was 1.0
      disc diameter (range, 0.5-2.5 disc diameters). The most common location was along
      the arcades (41.5%), adjacent to the optic nerve (29.2%), and in the retinal
      periphery (27.7%). In the CCF-TSCP group, AP was observed in 12.0% of patients
      (40.0% bilateral, 50.0% multiple). The presence of retinal features was
      associated with giant cell astrocytoma (37.1% vs. 14.6%; P = 0.018), renal
      angiomyolipoma (60.0% vs. 27.1%; P = 0.003), cognitive impairment (77.1% vs.
      43.8%; P = 0.002), and epilepsy (91.4% vs. 70.8% (P = 0.022) in those with and
      without retinal findings, respectively. In patients with retinal findings in both
      the CCF-TSCP and TSC-A groups, mutations in TSC2 were more frequent than in TSC1,
      3.3 times and 5.8 times, respectively; in those without retinal findings, the
      relative rates were 0.67 times and 2.3 times, respectively. CONCLUSIONS:
      Individuals with retinal findings are more likely to have concomitant
      subependymal giant cell astrocytomas, renal angiomyolipomas, cognitive
      impairment, and epilepsy. TSC2 mutations are more frequent in patients with
      retinal findings than in those without retinal findings.

PMID- 22608478
TI  - Reduction in intraocular pressure after cataract extraction: the Ocular
      Hypertension Treatment Study.
AB  - PURPOSE: To determine the change in intraocular pressure (IOP) after cataract
      extraction in the observation group of the Ocular Hypertension Treatment Study.
      DESIGN: Comparative case series. PARTICIPANTS: Forty-two participants (63 eyes)
      who underwent cataract surgery in at least 1 eye during the study and a control
      group of 743 participants (743 eyes) who did not undergo cataract surgery.
      METHODS: We defined the "split date" as the study visit date at which cataract
      surgery was reported in the cataract surgery group and a corresponding date in
      the control group. Preoperative IOP was defined as the mean IOP of up to 3 visits
      before the split date. Postoperative IOP was the mean IOP of up to 3 visits
      including the split date (0, 6, and 12 months' with "0 months" equaling the split
      date). In both groups, we censored data after initiation of ocular hypotensive
      medication or glaucoma surgery of any kind. MAIN OUTCOME MEASURES: Difference in
      preoperative and postoperative IOP. RESULTS: In the cataract group, postoperative
      IOP was significantly lower than the preoperative IOP (19.8 +/- 3.2 mmHg vs. 23.9
      +/- 3.2 mmHg; P<0.001). The postoperative IOP remained lower than the
      preoperative IOP for at least 36 months. The average decrease in postoperative
      IOP from preoperative IOP was 16.5%, and 39.7% of eyes had postoperative IOP >=
      20% below preoperative IOP. A greater reduction in postoperative IOP occurred in
      the eyes with the highest preoperative IOP. In the control group, the
      corresponding mean IOPs were 23.8 +/- 3.6 before the split date and 23.4 +/- 3.9
      after the split date. CONCLUSIONS: Cataract surgery decreases IOP in patients
      with ocular hypertension over a long period of time.

PMID- 22608479
TI  - Prevalence of age-related macular degeneration in elderly Caucasians: the Tromso
      Eye Study.
AB  - PURPOSE: To describe the sex- and age-specific prevalence of drusen, geographic
      atrophy, and neovascular age-related macular degeneration (AMD). DESIGN:
      Population-based, cross-sectional study. PARTICIPANTS: Caucasian adults aged 65
      to 87 years from the 6th Tromso Study, a population-based study conducted in 2007
      2008 in the municipality of Tromso, Norway. METHODS: Digital color fundus
      photographs were graded for predominant phenotype based on drusen size,
      geographic atrophy, and neovascular AMD. MAIN OUTCOME MEASURES: Age-related
      macular degeneration. RESULTS: A total of 3025 subjects participated; 89% of
      those were invited to the eye examinations. Gradable photographs were available
      for 2631 persons (mean age 72.3 years). Drusen 63-125 MUm as the predominant
      phenotype were found in 34.9% of participants (95% confidence interval [CI], 33.1
      36.8), drusen >125 MUm were found in 24.1% (95% CI, 22.5-25.8), geographic
      atrophy was found in 1.0% of participants (95% CI, 0.6-1.4), and neovascular AMD
      was found in 2.5% of participants (95% CI, 1.9-3.1). Bilateral involvement of
      late AMD was present in 1.1% of the sample. Eyes with late AMD had a
      significantly lower refractive error (spherical equivalent 0.078 vs. 0.99
      diopters, P<0.0001), and 42.5% of eyes had Snellen visual acuity <= 0.32.
      CONCLUSIONS: The prevalence of AMD among the elderly persons in this study was
      similar to rates in other Caucasian populations. Late AMD was present in 10.9% of
      subjects aged 80 years or more. No sex differences in prevalence rates of large
      drusen or late AMD were observed. Lower refractive error was observed in eyes
      with late AMD than in eyes without late AMD.

PMID- 22608480
TI  - Oral administration of fermented red ginseng suppressed ovalbumin-induced
      allergic responses in female BALB/c mice.
AB  - Anti-allergic efficacy of red ginseng (RG) and fermented red ginseng (FRG) was
      evaluated. RG or FRG were administered to ovalbumin (OVA)-sensitized mice for 8
      weeks. Immunoglobulins (Igs), Th1/Th2 type cytokines, and beta-lactoglobulin
      (BLG) in serum, and intestinal barrier-related molecules in jejunum were measured
      using enzyme-linked immunosorbent assay or reverse transcription-polymerase chain
      reaction. Mice sensitized with OVA increased serum IgG1, IgE, OVA-IgG1, and OVA
      IgE. Both RG and FRG decreased serum IgE, OVA-IgE, and pro-inflammatory
      cytokines. Serum BLG, a marker of gut permeability, was significantly higher in
      sensitized animals and was decreased in mice fed RG or FRG. In addition,
      intestinal barrier-related markers such as MMCP-1, IL-4, TNF-alpha, COX-2, and
      iNOS mRNA expressions were decreased by RG or FRG. Our results suggest in vivo
      anti-allergic activities of RG or FRG, which are associated with the regulation
      of Th1/Th2 balance, intestinal inflammation and subsequent the suppression of
      IgE.

PMID- 22608481
TI  - First clinical trial of tomographic neurofeedback in attention
      deficit/hyperactivity disorder: evaluation of voluntary cortical control.
AB  - OBJECTIVE: Tomographic neurofeedback (tNF) training was evaluated as a treatment
      for attention-deficit/hyperactivity disorder (ADHD). To investigate the
      specificity of the treatment, outcomes were related to learning during tNF.
      METHODS: Thirteen children with ADHD trained over 36 lessons to regulate their
      brain activity in the anterior cingulate cortex (ACC) using both theta-beta
      frequency and slow cortical potential (SCP) protocols. Thirty-channel
      electroencephalogram (EEG) was used to calculate low-resolution electromagnetic
      tNF and to assess the course of the training. Pre- and post-assessments included
      questionnaires, tests of attention, EEG recordings, and cognitive event-related
      potentials. RESULTS: Despite behavioural improvement and EEG artefact reduction,
      only partial learning was found for ACC parameters. Successful regulation was
      observed only for a simple feedback variant of SCP training, but with ACC
      specific effects. Over training, resting EEG analysis indicated individual
      frequency normalisation rather than unidirectional changes across subjects.
      CONCLUSIONS: These results indicate that clinical improvement after ACC-tNF
      training can parallel artefact reduction without substantial learning of improved
      cortical control. However, individual normalisation of resting EEG activity and
      partial SCP control proved possible in this specific brain region affected in
      ADHD using tNF. Further studies are needed to clarify which critical aspects
      mediate region-specific learning in neurofeedback. SIGNIFICANCE: This study is
      the first to systematically investigate tNF in children suffering from a
      psychiatric disorder.

PMID- 22608482
TI  - Use of Bayesian MUNE to show differing rate of loss of motor units in subgroups
      of ALS.
AB  - OBJECTIVES: To evaluate differences among patients with different clinical
      features of ALS, we used our Bayesian method of motor unit number estimation
      (MUNE). METHODS: We performed serial MUNE studies on 42 subjects who fulfilled
      the diagnostic criteria for ALS during the course of their illness. Subjects were
      classified into three subgroups according to whether they had typical ALS (with
      upper and lower motor neurone signs) or had predominantly upper motor neurone
      weakness with only minor LMN signs, or predominantly lower motor neurone weakness
      with only minor UMN signs. In all subjects we calculated the half life of MUs,
      defined as the expected time for the number of MUs to halve, in one or more of
      the abductor digiti minimi (ADM), abductor pollicis brevis (APB) and extensor
      digitorum brevis (EDB) muscles. RESULTS: The mean half life of MUs was less in
      subjects who had typical ALS with both upper and lower motor neurone signs than
      in those with predominantly upper motor neurone weakness or predominantly lower
      motor neurone weakness. In 18 subjects we analysed the estimated size of the MUs
      and demonstrated the appearance of large MUs in subjects with upper or lower
      motor neurone predominant weakness. We found that the appearance of large MUs was
      correlated with the half life of MUs. CONCLUSIONS: Patients with different
      clinical features of ALS have different rates of loss and different sizes of MUs.
      SIGNIFICANCE: These findings could indicate differences in disease pathogenesis.

PMID- 22608483
TI  - Slowing of M1 oscillations in brain tumor patients in resting state and during
      movement.
AB  - OBJECTIVE: Brain tumors may severely disrupt the structure and function of the
      brain. While abnormal low-frequency activity can be found around tumor borders,
      disrupted structural connectivity may also impinge on neural activity in distant
      brain regions and other frequency bands. We investigated how glioma in patients
      with normal motor functioning affects activity in primary motor areas (M1).
      METHODS: Using magnetoencephalography in 12 patients with unilateral glioma
      located around the central sulcus, we studied activity in bilateral M1s in
      resting state and during movement with focus on motor-related mu (8-12Hz) and
      beta rhythms (15-30Hz). Principal component analysis served to test for
      differences in spectral content. RESULTS: A shift was found towards lower
      frequencies for M1 in the tumor hemisphere compared to M1 in the healthy
      hemisphere, caused by an increase in mu and decrease in beta power. This pattern
      was observed both in resting state and during movement. CONCLUSIONS: This
      'slowing' of brain oscillations in M1 resembles findings in patients with
      monohemispheric stroke and Parkinson's disease. A loss of intra-cortical
      connectivity may account for these findings, possibly supplemented by tumor
      induced changes in neurotransmitter systems. SIGNIFICANCE: Motor functioning may
      be unaffected by a spectral shift of mu and beta oscillations.

PMID- 22608484
TI  - Monitoring brain maturation in extremely premature infants.

PMID- 22608485
TI  - Dynamic imaging of seizure activity in pediatric epilepsy patients.
AB  - OBJECTIVE: To investigate the feasibility of using noninvasive EEG source imaging
      approach to image continuous seizure activity in pediatric epilepsy patients.
      METHODS: Nine pediatric patients with medically intractable epilepsy were
      included in this study. Eight of the patients had extratemporal lobe epilepsy and
      one had temporal lobe epilepsy. All of the patients underwent resective surgery
      and seven of them underwent intracranial EEG (iEEG) monitoring. The ictal EEG was
      analyzed using a noninvasive dynamic seizure imaging (DSI) approach. The DSI
      approach separates scalp EEGs into independent components and extracts the spatio
      temporal ictal features to achieve dynamic imaging of seizure sources. Surgical
      resection and intracranial recordings were used to validate the noninvasive
      imaging results. RESULTS: The DSI determined seizure onset zones (SOZs) in these
      patients were localized within or in close vicinity to the surgically resected
      region. In the seven patients with intracranial monitoring, the estimated seizure
      onset sources were concordant with the seizure onset zones of iEEG. The DSI also
      localized the multiple foci involved in the later seizure propagation, which were
      confirmed by the iEEG recordings. CONCLUSIONS: Dynamic seizure imaging can
      noninvasively image the seizure activations in pediatric patients with both
      temporal and extratemporal lobe epilepsy. SIGNIFICANCE: EEG seizure imaging can
      potentially be used to noninvasively image the SOZs and aid the pre-surgical
      planning in pediatric epilepsy patients.

PMID- 22608486
TI  - Synchronized finger exercise reduces surround inhibition.
AB  - OBJECTIVE: To investigate whether hand muscle repetitive use reduces surround
      inhibition (SI) as observed in patients with focal hand dystonia, we performed a
      transcranial magnetic stimulation (TMS) study in 15 healthy right-handed
      volunteers. METHODS: TMS was set to be triggered by self-initiated flexion of the
      index finger at 3ms after movement onset. Motor evoked potentials (MEPs) of the
      abductor digiti minimi (ADM) were measured before and at 0, 10, 20 and 30min
      after 'single' (little finger abduction) and 'dual' (both index finger flexion
      and little finger abduction) exercise at 0.5Hz for 30min. SI was calculated as
      (mean control MEP - mean self-triggered MEP)*100/mean control MEP. RESULTS:
      Compared to single exercise, dual exercise produced significantly larger and
      longer-lasting enhancements of self-triggered MEPs, and greater reduction in
      calculated SIs. CONCLUSIONS: This result demonstrates that synchronized finger
      exercise can reduce SI between the involved muscles possibly due either to the
      strengthening of the excitatory connections or to the weakening of the inhibitory
      connections between them, and may illustrate the association between hand muscle
      repetitive use and disturbed SI observed in FHD. SIGNIFICANCE: The operation of
      surround inhibition can be reduced by practicing synchronous movements.

PMID- 22608487
TI  - Paired associative stimulation increases motor cortex excitability more
      effectively than theta-burst stimulation.
AB  - OBJECTIVE: To examine the effects of theta burst stimulation (TBS) and paired
      associative stimulation (PAS) on excitability in the human motor cortex. METHODS:
      Sixteen healthy young participants received intermittent TBS (iTBS) or PAS to the
      primary motor cortex on two testing occasions, at least a week apart. Ten of the
      participants also received iTBS or PAS after conditioning with continuous TBS on
      two other occasions. Cortical excitability was assessed with single TMS pulses to
      the motor cortex. Motor evoked potentials (MEPs) were measured from the first
      dorsal interosseus (FDI) muscle before TBS or PAS stimulation, and every 10min
      for 60min after stimulation. Changes in excitability were compared against the
      potential for motor learning, assessed with the rotor pursuit task. RESULTS:
      After the PAS protocol MEP amplitudes were significantly increased. This increase
      was greater than after intermittent TBS, which did not change MEPs significantly.
      Conditioning with continuous TBS showed no significant effect. Participants'
      responses were not correlated across protocols and were not correlated with rotor
      pursuit learning. CONCLUSIONS: PAS was the only protocol which induced
      significant increases in MEP amplitude. SIGNIFICANCE: PAS is robust in inducing
      excitatory cortical change. This makes it a suitable protocol for testing
      plasticity in healthy and patient groups.

PMID- 22608489
TI  - [Improving the diagnosis of toxigenic Clostridium difficile infection].

PMID- 22608490
TI  - [Hepatitis E: scale of the problem in Spain].
AB  - Hepatitis E virus (HEV) infection is one of the most frequent causes of acute
      hepatitis worldwide. However, in Spain, HEV causes only a tiny number of cases of
      acute hepatitis, the most prevalent cause being hepatitis A. Most cases of HEV in
      Spain are "imported", being acquired through travel to areas where this infection
      is endemic. Nevertheless, in the last few years a growing number of
      "autochthonous cases" have been reported in persons with no history of travelling
      to HEV-endemic areas. The prevalence of IgG antibodies against HEV, indicating
      exposure to this virus, is approximately 0.6-7.3% in the general population in
      Spain and is 19% in persons with risk factors such as exposure to pigs.

PMID- 22608491
TI  - A case of esophageal complication in epidermolysis bulhosa simplex.
AB  - It is well known the involvement of the gastrointestinal tract in Epidermolysis
      Bulhosa (EB) and its consequences on both nutrition and growth. We present a case
      of a young girl with EB diagnosed soon after birth, admitted to our emergency
      room with food impactation. The endoscopy revealed a double barrel esophagus. No
      medical or surgical therapy was started and after 2 months of enteric feeding,
      spontaneous resolution was observed at endoscopy. Skin biopsy was compatible with
      EB Simplex. According to the literature EB Simplex is the subtype the least
      associated with GI tract involvement, presenting with dysphagia in only 2% of the
      patients, and with the lowest cumulative risk of esophageal stricturing.
      CONCLUSION: We present an unusual case of EB simplex involvement of the esophagus
      with spontaneous resolution of a false lumen, with clinical improvement of the
      patient.

PMID- 22608492
TI  - [Octreotide treatment for postoperative chylous ascites in an adult].
AB  - Chylous ascites is infequent after abdominal surgery. We describe the case of a
      43-year-old man with portal cavernomatosis who underwent surgery to insert a
      splenorenal shunt, which was not placed due to the absence of signs of portal
      hypertension. On postoperative day 20, the patient developed abdominal distension
      and mild dyspnea and was diagnosed with chylous ascites, which was related to the
      surgery. The patient was initially treated with diet and diuretics, with no
      clinical response, and consequently octreotide therapy was started. Four days
      later, the ascites was almost resolved and an ultrasound scan at 4 months showed
      its complete disappearance. This article demonstrates the effectiveness of
      octreotide in the treatment of postsurgical chylous ascites.

PMID- 22608493
TI  - [Chronic pancreatitis: beyond alcohol].
AB  - For many years, the classification of chronic pancreatitis has been
      oversimplified according to whether the cause is alcoholic (60-70% of cases
      according to published series) or non-alcoholic (20-40% of the remaining cases).
      Recognition of smoking as an important risk factor and increasing identification
      of factors of genetic susceptibility have placed these percentages in doubt and
      have led to a reconceptualization of the disease as a multifactorial process.
      Mutations in the PRSS1, SPINK1 and CFTR genes have been confirmed as major risk
      factors, while mutations in the CTRC and CASR genes are considered lesser risk
      factors for the development of chronic pancreatitis. These genetic variants are
      expressed in a much higher percentage of patients with chronic pancreatitis than
      could be expected by chance. The trans-heterozygous combination multiplies the
      risk of chronic pancreatitis and demonstrates the degree of complexity of the
      etiopathogenic mechanisms of the disease. Ductal obstruction and autoimmunity are
      other important etiologic factors of chronic pancreatitis that need a specific
      review. The present article reviews the latest studies evaluating the role of
      alcohol and smoking in chronic pancreatitis and the most significant genetic
      factors.

PMID- 22608494
TI  - Antioxidant supplementation attenuates oxidative stress in chronic hepatitis C
      patients.
AB  - Reactive oxygen species (ROS) overgeneration is involved in the pathogenesis of
      hepatitis C. The aim of this study was to evaluate the antioxidant status in the
      blood of HCV infected patients treated or not with standard therapy before and
      after supplementation of vitamins E, C and zinc. Biomarkers of oxidative stress
      were evaluated in the blood of three groups of patients: group 1 - controls;
      group 2 - HCV patients without treatment examined before and after a daily
      antioxidant supplementation (vitamin E 800 mg, C 500 mg and zinc 40 mg) for 6
      months; and group 3 - HCV patients treated with pegylated interferon combined
      with ribavirin, also examined before and after the same antioxidant
      supplementation. Before antiviral treatment HCV patients showed enhanced
      superoxide dismutase, catalase and glutathione peroxidase activities and
      decreased glutathione reductase activity, while lipoperoxidation was increased
      and reduced glutathione showed decreased levels compared to controls. Treatment
      with standard therapy enhanced the activities of catalase and glutathione S
      transferase, increased contents of protein carbonyl and promoted further reduced
      glutathione depletion. After antioxidant supplementation, decreased catalase and
      glutathione S-transferase activities, decreased lipoperoxidation in group 2, and
      increased reduced glutathione contents in both supplemented groups were detected.
      Before antioxidant supplementation, alanine aminotransferase and gamma glutamyl
      transferase contents showed significant increases in group 2. CONCLUSION:
      Untreated HCV patients and also those treated with the standard therapy are
      coping with a systemic oxidative stress. The antioxidant supplementation
      conferred an antioxidant protection to both supplemented groups attenuating
      oxidation processes related to the disease.

PMID- 22608495
TI  - Integrin alpha5beta1 activates the NLRP3 inflammasome by direct interaction with
      a bacterial surface protein.
AB  - Integrins are cell-surface heterodimeric glycoproteins composed of alpha and beta
      subunits that mediate cell-cell, cell-extracellular matrix, and cell-pathogen
      interactions. In this study, we report a specific role of integrin alpha5beta1 in
      NLRP3 inflammasome activation in macrophages stimulated by Td92, a surface
      protein of the periodontopathogen, Treponema denticola. The direct interaction of
      Td92 with the cell membrane integrin alpha5beta1 resulted in ATP release and K(+)
      efflux, which are the main events in NLRP3 activation. This interaction was
      arginine-glycine-aspartate (RGD)-independent, and Td92 internalization was not
      required for the activity. An integrin alpha5beta1 antibody and oxATP, an ATP
      receptor antagonist, inhibited NLRP3 expression, caspase-1 activation,
      interleukin-1beta (IL-1beta) secretion, and proIL-1beta synthesis, all of which
      were regulated by NF-kappaB activation. Therefore, our data has identified the
      integrin alpha5beta1 as a principal cell membrane receptor for both NLRP3
      inflammasome activation and IL-1beta transcription by a bacterial protein, which
      could exaggerate inflammation, a characteristic of periodontitis.

PMID- 22608497
TI  - Disruption of Fnip1 reveals a metabolic checkpoint controlling B lymphocyte
      development.
AB  - The coordination of nutrient and energy availability with cell growth and
      division is essential for proper immune cell development and function. By using a
      chemical mutagenesis strategy in mice, we identified a pedigree that has a
      complete block in B cell development at the pre-B cell stage resulting from a
      deletion in the Fnip1 gene. Enforced expression of an immunoglobulin transgene
      failed to rescue B cell development. Whereas essential pre-B cell signaling
      molecules were activated normally in Fnip1-null pre-B cells, the metabolic
      regulators AMPK and mTOR were dysregulated, resulting in excessive cell growth
      and enhanced sensitivity to apoptosis in response to metabolic stress (pre-B cell
      receptor crosslinking, oncogene activation). These results indicate that
      Folliculin-interacting protein 1 (Fnip1) is vital for B cell development and
      metabolic homeostasis and reveal a metabolic checkpoint that may ensure that pre
      B cells have sufficient metabolic capacity to support division, while limiting
      lymphomagenesis caused by deregulated growth.

PMID- 22608496
TI  - Epithelial cell-specific Act1 adaptor mediates interleukin-25-dependent helminth
      expulsion through expansion of Lin(-)c-Kit(+) innate cell population.
AB  - Interleukin-25 (IL-25 or IL-17E), a member of the structurally related IL-17
      family, functions as an important mediator of T helper 2 cell-type (type 2)
      responses. We examined the cell type-specific role of IL-25-induced Act1-mediated
      signaling in protective immunity against helminth infection. Targeted Act1
      deficiency in epithelial cells resulted in a marked delay in worm expulsion and
      abolished the expansion of the Lin(-)c-Kit(+) innate cell population in the
      mesenteric lymph node, lung, and liver. Th2 cell-inducing cytokine (IL-25 and IL
      33) expression were reduced in the intestinal epithelial cells from the infected
      and IL-25-injected epithelial-specific Act1-deficient mice. Adoptive transfer of
      Lin(-)c-Kit(+) cells or combined injection of IL-25 and IL-33 restored the type 2
      responses in these mice. Taken together, these results suggest that epithelial
      specific Act1 mediates the expansion of the Lin(-)c-Kit(+) innate cell population
      through the positive-feedback loop of IL-25, initiating the type 2 immunity
      against helminth infection.

PMID- 22608498
TI  - Gene deregulation and chronic activation in natural killer cells deficient in the
      transcription factor ETS1.
AB  - Multiple transcription factors guide the development of mature functional natural
      killer (NK) cells, yet little is known about their function. We used global gene
      expression and genome-wide binding analyses combined with developmental and
      functional studies to unveil three roles for the ETS1 transcription factor in NK
      cells. ETS1 functions at the earliest stages of NK cell development to promote
      expression of critical transcriptional regulators including T-BET and ID2, NK
      cell receptors (NKRs) including NKp46, Ly49H, and Ly49D, and signaling molecules
      essential for NKR function. As a consequence, Ets1(-/-) NK cells fail to
      degranulate after stimulation through activating NKRs. Nonetheless, these cells
      are hyperresponsive to cytokines and have characteristics of chronic stimulation
      including increased expression of inhibitory NKRs and multiple activation
      associated genes. Therefore, ETS1 regulates a broad gene expression program in NK
      cells that promotes target cell recognition while limiting cytokine-driven
      activation.

PMID- 22608499
TI  - Mutations of the mitochondrial-tRNA modifier MTO1 cause hypertrophic
      cardiomyopathy and lactic acidosis.
AB  - Dysfunction of mitochondrial respiration is an increasingly recognized cause of
      isolated hypertrophic cardiomyopathy. To gain insight into the genetic origin of
      this condition, we used next-generation exome sequencing to identify mutations in
      MTO1, which encodes mitochondrial translation optimization 1. Two affected
      siblings carried a maternal c.1858dup (p.Arg620Lysfs(*)8) frameshift and a
      paternal c.1282G>A (p.Ala428Thr) missense mutation. A third unrelated individual
      was homozygous for the latter change. In both humans and yeast, MTO1 increases
      the accuracy and efficiency of mtDNA translation by catalyzing the 5
      carboxymethylaminomethylation of the wobble uridine base in three mitochondrial
      tRNAs (mt-tRNAs). Accordingly, mutant muscle and fibroblasts showed variably
      combined reduction in mtDNA-dependent respiratory chain activities. Reduced
      respiration in mutant cells was corrected by expressing a wild-type MTO1 cDNA.
      Conversely, defective respiration of a yeast mto1Delta strain failed to be
      corrected by an Mto1(Pro622*) variant, equivalent to human MTO1(Arg620Lysfs*8),
      whereas incomplete correction was achieved by an Mto1(Ala431Thr) variant,
      corresponding to human MTO1(Ala428Thr). The respiratory yeast phenotype was
      dramatically worsened in stress conditions and in the presence of a paromomycin
      resistant (P(R)) mitochondrial rRNA mutation. Lastly, in vivo mtDNA translation
      was impaired in the mutant yeast strains.

PMID- 22608500
TI  - Evolutionary history of copy-number-variable locus for the low-affinity Fcgamma
      receptor: mutation rate, autoimmune disease, and the legacy of helminth
      infection.
AB  - Both sequence variation and copy-number variation (CNV) of the genes encoding
      receptors for immunoglobulin G (Fcgamma receptors) have been genetically and
      functionally associated with a number of autoimmune diseases. However, the
      molecular nature and evolutionary context of this variation is unknown. Here, we
      describe the structure of the CNV, estimate its mutation rate and diversity, and
      place it in the context of the known functional alloantigen variation of these
      genes. Deletion of Fcgamma receptor IIIB, associated with systemic lupus
      erythematosus, is a result of independent nonallelic homologous recombination
      events with a frequency of approximately 0.1%. We also show that pathogen
      diversity, in particular helminth diversity, has played a critical role in
      shaping the functional variation at these genes both between mammalian species
      and between human populations. Positively selected amino acids are involved in
      the interaction with IgG and include some amino acids that are known polymorphic
      alloantigens in humans. This supports a genetic contribution to the hygiene
      hypothesis, which states that past evolution in the context of helminth diversity
      has left humans with an array of susceptibility alleles for autoimmune disease in
      the context of a helminth-free environment. This approach shows the link between
      pathogens and autoimmune disease at the genetic level and provides a strategy for
      interrogating the genetic variation underlying autoimmune-disease risk and
      infectious-disease susceptibility.

PMID- 22608501
TI  - Strikingly different clinicopathological phenotypes determined by progranulin
      mutation dosage.
AB  - We performed hypothesis-free linkage analysis and exome sequencing in a family
      with two siblings who had neuronal ceroid lipofuscinosis (NCL). Two linkage peaks
      with maximum LOD scores of 3.07 and 2.97 were found on chromosomes 7 and 17,
      respectively. Unexpectedly, we found these siblings to be homozygous for a
      c.813_816del (p.Thr272Serfs*10) mutation in the progranulin gene (GRN, granulin
      precursor) in the latter peak. Heterozygous mutations in GRN are a major cause of
      frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP), the second
      most common early-onset dementia. Reexamination of progranulin-deficient mice
      revealed rectilinear profiles typical of NCL. The age-at-onset and neuropathology
      of FTLD-TDP and NCL are markedly different. Our findings reveal an unanticipated
      link between a rare and a common neurological disorder and illustrate pleiotropic
      effects of a mutation in the heterozygous or homozygous states.

PMID- 22608504
TI  - [Anomalous origin of left coronary artery: a malignant interarterial variant with
      a benign clinical course].
AB  - Anomalous origin of coronary arteries represents a clinical challenge not only
      because of the anatomical variability, but also the possible functional
      consequences, pathophysiological mechanisms involved and the absence of large
      series in the literature that would provide evidence for clinical and therapeutic
      orientation. The authors describe the case of a 55-year-old male patient with a
      long history of atypical chest pain who was considered to have a low to
      intermediate likelihood of coronary artery disease. Therefore, and also bearing
      in mind his physical limitations (congenital left leg atrophy), he was referred
      for cardiac CT to rule out coronary artery disease. The exam showed a left
      coronary artery arising from the right coronary cusp and with an interarterial
      course, between the aorta and pulmonary trunk. Although this is a potentially
      malignant anatomical variant with surgical indication, a conservative approach
      was chosen, considering the late diagnosis and particular risk-benefit profile.

PMID- 22608502
TI  - Deleterious mutations in LRBA are associated with a syndrome of immune deficiency
      and autoimmunity.
AB  - Most autosomal genetic causes of childhood-onset hypogammaglobulinemia are
      currently not well understood. Most affected individuals are simplex cases, but
      both autosomal-dominant and autosomal-recessive inheritance have been described.
      We performed genetic linkage analysis in consanguineous families affected by
      hypogammaglobulinemia. Four consanguineous families with childhood-onset humoral
      immune deficiency and features of autoimmunity shared genotype evidence for a
      linkage interval on chromosome 4q. Sequencing of positional candidate genes
      revealed that in each family, affected individuals had a distinct homozygous
      mutation in LRBA (lipopolysaccharide responsive beige-like anchor protein). All
      LRBA mutations segregated with the disease because homozygous individuals showed
      hypogammaglobulinemia and autoimmunity, whereas heterozygous individuals were
      healthy. These mutations were absent in healthy controls. Individuals with
      homozygous LRBA mutations had no LRBA, had disturbed B cell development,
      defective in vitro B cell activation, plasmablast formation, and immunoglobulin
      secretion, and had low proliferative responses. We conclude that mutations in
      LRBA cause an immune deficiency characterized by defects in B cell activation and
      autophagy and by susceptibility to apoptosis, all of which are associated with a
      clinical phenotype of hypogammaglobulinemia and autoimmunity.

PMID- 22608503
TI  - Cantu syndrome is caused by mutations in ABCC9.
AB  - Cantu syndrome is a rare disorder characterized by congenital hypertrichosis,
      neonatal macrosomia, a distinct osteochondrodysplasia, and cardiomegaly. Using an
      exome-sequencing approach applied to one proband-parent trio and three unrelated
      single cases, we identified heterozygous mutations in ABCC9 in all probands. With
      the inclusion of the remaining cohort of ten individuals with Cantu syndrome, a
      total of eleven mutations in ABCC9 were found. The de novo occurrence in all six
      simplex cases in our cohort substantiates the presence of a dominant disease
      mechanism. All mutations were missense, and several mutations affect Arg1154.
      This mutation hot spot lies within the second type 1 transmembrane region of this
      ATP-binding cassette transporter protein, which may suggest an activating
      mutation. ABCC9 encodes the sulfonylurea receptor (SUR) that forms ATP-sensitive
      potassium channels (K(ATP) channels) originally shown in cardiac, skeletal, and
      smooth muscle. Previously, loss-of-function mutations in this gene have been
      associated with idiopathic dilated cardiomyopathy type 10 (CMD10). These findings
      identify the genetic basis of Cantu syndrome and suggest that this is a new
      member of the potassium channelopathies.

PMID- 22608505
TI  - [Loeffler's endocarditis--a case report].
AB  - Loeffler's endocarditis is an acute form of primary restrictive cardiomyopathy.
      We report the case of a young woman with pleuritic chest pain associated with
      fever and hypereosinophilia. She was hospitalized with suspected acute
      myopericarditis and was treated with aspirin, leading to clinical improvement.
      Ten days after discharge, she was rehospitalized due to recurrence of chest pain.
      The echocardiogram showed what appeared to be a mass filling the apex of the
      right ventricle (RV). She was referred for magnetic resonance imaging, which
      revealed marked myocardial thickening in the apex of the RV. The patient
      underwent an endomyocardial biopsy, resulting in a diagnosis of eosinophilic
      endocarditis. After treatment with prednisolone, all symptoms and the
      eosinophilia disappeared, and there was complete remission of the RV
      abnormalities. After three years of follow-up, the patient remains asymptomatic.
      This case shows that, even without an etiologic diagnosis of eosinophilia, the
      prognosis for Loeffler's endocarditis can be favorable if treatment is initiated
      early.

PMID- 22608506
TI  - Gamete fusion is required to block multiple pollen tubes from entering an
      Arabidopsis ovule.
AB  - In double fertilization, a reproductive system unique to flowering plants, two
      immotile sperm are delivered to an ovule by a pollen tube. One sperm fuses with
      the egg to generate a zygote, the other with the central cell to produce
      endosperm. A mechanism preventing multiple pollen tubes from entering an ovule
      would ensure that only two sperm are delivered to female gametes. We use live
      cell imaging and a novel mixed-pollination assay that can detect multiple pollen
      tubes and multiple sets of sperm within a single ovule to show that Arabidopsis
      efficiently prevents multiple pollen tubes from entering an ovule. However, when
      gamete-fusion defective hap2(gcs1) or duo1 sperm are delivered to ovules, as many
      as three additional pollen tubes are attracted. When gamete fusion fails, one of
      two pollen tube-attracting synergid cells persists, enabling the ovule to attract
      more pollen tubes for successful fertilization. This mechanism prevents the
      delivery of more than one pair of sperm to an ovule, provides a means of
      salvaging fertilization in ovules that have received defective sperm, and ensures
      maximum reproductive success by distributing pollen tubes to all ovules.

PMID- 22608507
TI  - Attention modulates spinal cord responses to pain.
AB  - Reduced pain perception while being distracted from pain is an everyday example
      of how cognitive processes can interfere with pain perception. Previous
      neuroimaging studies showed distraction-related modulations of pain-driven
      activations in various cortical and subcortical brain regions, but the precise
      neuronal mechanism underlying this phenomenon is unclear. Using high-resolution
      functional magnetic resonance imaging of the human cervical spinal cord in
      combination with thermal pain stimulation and a well-established working memory
      task, we demonstrate that this phenomenon relies on an inhibition of incoming
      pain signals in the spinal cord. Neuronal responses to painful stimulation in the
      dorsal horn of the corresponding spinal segment were significantly reduced under
      high working memory load compared to low working memory load. At the individual
      level, reductions of neuronal responses in the spinal cord predicted behavioral
      pain reductions. In a subsequent behavioral experiment, using the opioid
      antagonist naloxone in a double-blind crossover design with the same paradigm, we
      demonstrate a substantial contribution of endogenous opioids to this mechanism.
      Taken together, our results show that the reduced pain experience during mental
      distraction is related to a spinal process and involves opioid neurotransmission.

PMID- 22608508
TI  - The role of a pseudo-response regulator gene in life cycle adaptation and
      domestication of beet.
AB  - Life cycle adaptation to latitudinal and seasonal variation in photoperiod and
      temperature is a major determinant of evolutionary success in flowering plants.
      Whereas the life cycle of the dicotyledonous model species Arabidopsis thaliana
      is controlled by two epistatic genes, FLOWERING LOCUS C and FRIGIDA, three
      unrelated loci (VERNALIZATION) determine the spring and winter habits of
      monocotyledonous plants such as temperate cereals. In the core eudicot species
      Beta vulgaris, whose lineage diverged from that leading to Arabidopsis shortly
      after the monocot-dicot split 140 million years ago, the bolting locus B is a
      master switch distinguishing annuals from biennials. Here, we isolated B and show
      that the pseudo-response regulator gene BOLTING TIME CONTROL 1 (BvBTC1), through
      regulation of the FLOWERING LOCUS T genes, is absolutely necessary for flowering
      and mediates the response to both long days and vernalization. Our results
      suggest that domestication of beets involved the selection of a rare partial loss
      of-function BvBTC1 allele that imparts reduced sensitivity to photoperiod that is
      restored by vernalization, thus conferring bienniality, and illustrate how
      evolutionary plasticity at a key regulatory point can enable new life cycle
      strategies.

PMID- 22608509
TI  - Fertilization recovery after defective sperm cell release in Arabidopsis.
AB  - In animal fertilization, multiple sperms typically arrive at an egg cell to "win
      the race" for fertilization. However, in flowering plants, only one of many
      pollen tubes, conveying plant sperm cells, usually arrives at each ovule that
      harbors an egg cell. Plant fertilization has thus been thought to depend on the
      fertility of a single pollen tube. Here we report a fertilization recovery
      phenomenon in flowering plants that actively rescues the failure of fertilization
      of the first mutant pollen tube by attracting a second, functional pollen tube.
      Wild-type (WT) ovules of Arabidopsis thaliana frequently (~80%) accepted two
      pollen tubes when entered by mutant pollen defective in gamete fertility. In
      typical flowering plants, two synergid cells on the side of the egg cell attract
      pollen tubes, one of which degenerates upon pollen tube discharge. By semi-in
      vitro live-cell imaging we observed that fertilization was rescued when the
      second synergid cell accepted a WT pollen tube. Our results suggest that
      flowering plants precisely control the number of pollen tubes that arrive at each
      ovule and employ a fertilization recovery mechanism to maximize the likelihood of
      successful seed set.

PMID- 22608510
TI  - Mechanism for astral microtubule capture by cortical Bud6p priming spindle
      polarity in S. cerevisiae.
AB  - BACKGROUND: Budding yeast is a unique model to dissect spindle orientation in a
      cell dividing asymmetrically. In yeast, this process begins with the capture of
      pole-derived astral microtubules (MTs) by the polarity determinant Bud6p at the
      cortex of the bud in G(1). Bud6p couples MT growth and shrinkage with spindle
      pole movement relative to the contact site. This activity resides in N-terminal
      sequences away from a domain linked to actin organization. Kip3p (kinesin-8), a
      MT depolymerase, may be implicated, but other molecular details are essentially
      unknown. RESULTS: We show that Bud6p and Kip3p play antagonistic roles in
      controlling the length of MTs contacting the bud. The stabilizing role of Bud6p
      required the plus-end-tracking protein Bim1p (yeast EB1). Bim1p bound Bud6p N
      terminus, an interaction that proved essential for cortical capture of MTs in
      vivo. Moreover, Bud6p influenced Kip3p dynamic distribution through its effect on
      MT stability during cortical contacts via Bim1p. Coupling between Kip3p-driven
      depolymerization and shrinkage at the cell cortex required Bud6p, Bim1p, and
      dynein, a minus-end-directed motor helping tether the receding plus ends to the
      cell cortex. Validating these findings, live imaging of the interplay between
      dynein and Kip3p demonstrated that both motors decorated single astral MTs with
      dynein persisting at the plus end in association with the site of cortical
      contact during shrinkage at the cell cortex. CONCLUSIONS: Astral MT shrinkage
      linked to Bud6p involves its direct interaction with Bim1p and the concerted
      action of two MT motors-Kip3p and dynein.

PMID- 22608511
TI  - Septin-driven coordination of actin and microtubule remodeling regulates the
      collateral branching of axons.
AB  - Axon branching is fundamental to the development of the peripheral and central
      nervous system. Branches that sprout from the axon shaft are termed collateral or
      interstitial branches. Collateral branching of axons requires the formation of
      filopodia from actin microfilaments (F-actin) and their engorgement with
      microtubules (MTs) that splay from the axon shaft. The mechanisms that drive and
      coordinate the remodeling of actin and MTs during branch morphogenesis are poorly
      understood. Septins comprise a family of GTP-binding proteins that oligomerize
      into higher-order structures, which associate with membranes and the actin and
      microtubule cytoskeleton. Here, we show that collateral branching of axons
      requires SEPT6 and SEPT7, two interacting septins. In the axons of sensory
      neurons, both SEPT6 and SEPT7 accumulate at incipient sites of filopodia
      formation. We show that SEPT6 localizes to axonal patches of F-actin and
      increases the recruitment of cortactin, a regulator of Arp2/3-mediated actin
      polymerization, triggering the emergence of filopodia. Conversely, SEPT7 promotes
      the entry of axonal MTs into filopodia, enabling the formation of collateral
      branches. Surprisingly, septins provide a novel mechanism for the collateral
      branching of axons by coordinating the remodeling of the actin and microtubule
      cytoskeleton.

PMID- 22608512
TI  - Aggregative multicellularity evolved independently in the eukaryotic supergroup
      Rhizaria.
AB  - Multicellular forms of life have evolved many times, independently giving rise to
      a diversity of organisms such as animals, plants, and fungi that together
      comprise the visible biosphere. Yet multicellular life is far more widespread
      among eukaryotes than just these three lineages. A particularly common form of
      multicellularity is a social aggregative fruiting lifestyle whereby individual
      cells associate to form a "fungus-like" sorocarp. This complex developmental
      process that requires the interaction of thousands of cells working in concert
      was made famous by the "cellular slime mold"Dictyostelium discoideum, which
      became an important model organism. Although sorocarpic protistan lineages have
      been identified in five of the major eukaryote groups, the ubiquitous and
      globally distributed species Guttulinopsis vulgaris has eluded proper
      classification. Here we demonstrate, by phylogenomic analyses of a 159-protein
      data set, that G. vulgaris is a member of Rhizaria and is thus the first member
      of this eukaryote supergroup known to be capable of aggregative multicellularity.

PMID- 22608513
TI  - FMNL2 drives actin-based protrusion and migration downstream of Cdc42.
AB  - Cell migration entails protrusion of lamellipodia, densely packed networks of
      actin filaments at the cell front. Filaments are generated by nucleation, likely
      mediated by Arp2/3 complex and its activator Scar/WAVE. It is unclear whether
      formins contribute to lamellipodial actin filament nucleation or serve as
      elongators of filaments nucleated by Arp2/3 complex. Here we show that the
      Diaphanous-related formin FMNL2, also known as FRL3 or FHOD2, accumulates at
      lamellipodia and filopodia tips. FMNL2 is cotranslationally modified by
      myristoylation and regulated by interaction with the Rho-guanosine triphosphatase
      Cdc42. Abolition of myristoylation or Cdc42 binding interferes with proper FMNL2
      activation, constituting an essential prerequisite for subcellular targeting. In
      vitro, C-terminal FMNL2 drives elongation rather than nucleation of actin
      filaments in the presence of profilin. In addition, filament ends generated by
      Arp2/3-mediated branching are captured and efficiently elongated by the formin.
      Consistent with these biochemical properties, RNAi-mediated silencing of FMNL2
      expression decreases the rate of lamellipodia protrusion and, accordingly, the
      efficiency of cell migration. Our data establish that the FMNL subfamily member
      FMNL2 is a novel elongation factor of actin filaments that constitutes the first
      Cdc42 effector promoting cell migration and actin polymerization at the tips of
      lamellipodia.

PMID- 22608514
TI  - Genetic mapping and characterization of the globe artichoke (+)-germacrene A
      synthase gene, encoding the first dedicated enzyme for biosynthesis of the bitter
      sesquiterpene lactone cynaropicrin.
AB  - Globe artichoke (Cynara cardunculus var. scolymus L., Asteraceae) is a perennial
      crop traditionally consumed as a vegetable in the Mediterranean countries and
      rich in nutraceutically and pharmaceutically active compounds, including phenolic
      and terpenoid compounds. Its bitter taste is caused by its high content of
      sesquiterpene lactones (STLs), such as cynaropicrin. The biosynthetic pathway
      responsible for STL biosynthesis in globe artichoke is unknown, but likely
      proceeds through germacrene A, as has been shown for other Asteraceae species.
      Here, we investigated the accumulation of cynaropicrin in different tissues of
      globe artichoke, and compared it to accumulation of phenolic compounds.
      Cynaropicrin concentration was highest in old leaves. A putative germacrene A
      synthase (GAS) gene was identified in a set of ~19,000 globe artichoke unigenes.
      When heterologously expressed in Escherichia coli, the putative globe artichoke
      GAS converted farnesyl diphosphate (FPP) into (+)-germacrene A. Among various
      tissues assayed, the level of globe artichoke GAS expression was highest in
      mature (six week old) leaves. A sequence polymorphism within a mapping population
      parent allowed the corresponding GAS gene to be positioned on a genetic map. This
      study reports the isolation, expression and mapping of a key gene involved in STL
      biosynthesis in C. cardunculus. This is a good basis for further investigation of
      this pathway.

PMID- 22608515
TI  - Tetraspanin genes in plants.
AB  - Tetraspanins represent a four-transmembrane protein superfamily with a conserved
      structure and amino acid residues that are present in mammals, insects, fungi and
      plants. Tetraspanins interact with each other or with other membrane proteins to
      form tetraspanin-enriched microdomains that play important roles in development,
      pathogenesis and immune responses via facilitating cell-cell adhesion and fusion,
      ligand binding and intracellular trafficking. Here, we emphasize evolutionary
      aspects within the plant kingdom based on genomic sequence information. A
      phylogenetic tree based on 155 tetraspanin genes of 11 plant species revealed
      ancient and fast evolving clades. Tetraspanins were only present in multicellular
      plants, were often duplicated in the plant genomes and predicted by the
      electronic Fluorescent Pictograph for gene expression analysis to be either
      functionally redundant or divergent. Tetraspanins contain a large extracellular
      loop with conserved cysteines that provide the binding sites for the
      interactions. The Arabidopsis thaliana TETRASPANIN1/TORNADO2/EKEKO has a function
      in leaf and root patterning and TETRASPANIN3 was identified in the plasmodesmatal
      proteome, suggesting a role in cell-cell communication during plant development.

PMID- 22608516
TI  - Differential expression and functional characterization of the NADPH cytochrome
      P450 reductase genes from Nothapodytes foetida.
AB  - Three unique NADPH:cytochrome P450 reductase (CPR) cDNAs have been isolated from
      a Nothapodytes foetida cDNA library and characterized. Phylogenetic analysis
      showed that NfCPR1 is a class I isoform, whereas NfCPR2 and NfCPR3 are class II
      isoforms. Both NfCPR1 and NfCPR2 transcripts were detected in all examined organs
      of N. foetida, with the highest level for NfCPR1 being in the seeds whereas for
      NfCPR2 predominantly in leaves. In contrast, NfCPR3 transcripts were only
      detected in flower buds and seeds at almost equal expression levels. Moreover,
      NfCPR1 expression did not change during wounding treatment, whereas NfCPR2 and
      NfCPR3 were induced in response to wounding. Microsomes isolated from insect
      cells co-expressing NfCPR2 and cytochrome P450 enzyme geraniol 10-hydroxylase
      (G10H) enhanced the production of eriodictyol from naringenin approximately 11
      fold relative to control G10H-only insect cells, indicating the supportive role
      of NfCPR2 for G10H activity in insect cells.

PMID- 22608517
TI  - Iron biofortification in rice: it's a long way to the top.
AB  - Rice and most staple cereals contain low iron (Fe) levels, most of which is lost
      during grain processing. Populations with monotonous diets consisting mainly of
      cereals are especially prone to Fe deficiency, which affects about two billion
      people. Supplementation or food fortification programs have not always been
      successful. Crop Fe fertilization is also not very effective due to Fe soil
      insolubility. An alternative solution is Fe biofortification by generating
      cultivars that efficiently mobilize, uptake and translocate Fe to the edible
      parts. Here, we review the strategies used for the Fe biofortification of rice,
      including conventional breeding and directed genetic modification, which offer
      the most rapid way to develop Fe-rich rice plants. While classical breeding is
      able to modify the contents of inhibitors of Fe absorption, transgenic approaches
      have focused on enhanced Fe uptake from soil, xylem and phloem loading and grain
      sink strength. A comprehensive table is provided in which the percentages of the
      recommended dietary Fe intake reached by independently developed transgenic
      plants are calculated. In this review we also emphasize that the discovery of new
      QTLs and genes related to Fe biofortification is extremely important, but
      interdisciplinary research is needed for future success in this area.

PMID- 22608518
TI  - In vitro shoot organogenesis and hormone response are affected by the altered
      levels of Brassica napus meristem genes.
AB  - Arabidopsis shoot meristem activity is regulated by a molecular network involving
      the participation of several components, including SHOOTMERISTEMLESS (STM),
      CLAVATA1 (CLV1), and ZWILLE (ZLL). In an effort to identify the role of these
      genes during in vitro shoot formation Brassica and Arabidopsis plants were
      transformed with the Brassica napus (Bn) STM, CLV1, ZLL1 and ZLL2 identified in
      previous work [1]. In both systems shoot organogenesis was promoted by the over
      expression of BnSTM, BnZLL1, and BnZLL2, and repressed by the over-expression of
      BnCLV1. This distinct regulation, analogous to that occurring during in vivo
      meristem formation where STM and ZLL encourage stem cell formation while CLV1
      accelerates transition to differentiation, suggests similar regulatory mechanisms
      governing shoot formation in vivo and in vitro. While the BnZLL1 and BnZLL2
      induction of shoot organogenesis correlated only to changes in auxin signaling,
      BnSTM and BnCLV1 evoked major transcriptional alterations in cytokinin response.
      Besides increasing the transcript levels of two cytokinin receptors, ARABIDOPSIS
      HISTIDINE KINASE4 (AHK4) and CYTOKININ INDEPENDENT KINASE (CKI1), ectopic
      expression of BnSTM induced Type-B ARABIDOPSIS RESPONSE REGULATORS (ARRs) and
      repressed Type-A ARRs. Opposite transcriptional patterns occurred in explants
      over-expressing BnCLV1, characterized by a decreased ability to produce shoots.
      The role played by Type-A and Type-B ARRs during shoot organogenesis was further
      examined using a genetic approach which revealed the requirement of ARR12 for the
      BnSTM positive regulation of shoot organogenesis. Collectively these results
      expand our knowledge on the function of meristem genes, and provide new tools for
      enhancing in vitro propagation systems.

PMID- 22608519
TI  - In and out of the plant storage vacuole.
AB  - The plant storage vacuole is involved in a wide variety of metabolic functions a
      great many of which necessitate the transport of substances across the tonoplast.
      Some solutes, depending on the origin, have to cross the plasma membrane as well.
      The cell is equipped with a complex web of transport systems, cellular routes,
      and unique intracellular environments that support their transport and
      accumulation against a concentration gradient. These are capable of processing a
      diverse nature of substances of distinct sizes, chemical properties, and origins.
      In this review we describe the various mechanism involved in solute transport
      into the vacuole of storage cells with special emphasis placed on solutes
      arriving through the apoplast. Transport of solutes from the cytosol to the
      vacuole is carried out by tonoplast-bound ABC transporters, solute/H(+)
      antiporters, and ion channels whereas transport from the apoplast requires
      additional plasma membrane-bound solute/H(+) symporters and fluid-phase
      endocytosis. In addition, and based on new evidence accumulated within the last
      decade, we re-evaluate the current notion of extracellular solute uptake as
      partially based on facilitated diffusion, and offer an alternative interpretation
      that involves membrane bound transporters and fluid-phase endocytosis. Finally,
      we make several assertions in regards to solute export from the vacuole as
      predicted by the limited available data suggesting that both membrane-bound
      carriers and vesicle mediated exocytosis are involved during solute mobilization.

PMID- 22608520
TI  - The comparative chloroplast genomic analysis of photosynthetic orchids and
      developing DNA markers to distinguish Phalaenopsis orchids.
AB  - The chloroplast genome of Phalaenopsis equestris was determined and compared to
      those of Phalaenopsis aphrodite and Oncidium Gower Ramsey in Orchidaceae. The
      chloroplast genome of P. equestris is 148,959 bp, and a pair of inverted repeats
      (25,846 bp) separates the genome into large single-copy (85,967 bp) and small
      single-copy (11,300 bp) regions. The genome encodes 109 genes, including 4 rRNA,
      30 tRNA and 75 protein-coding genes, but loses four ndh genes (ndhA, E, F and H)
      and seven other ndh genes are pseudogenes. The rate of inter-species variation
      between the two moth orchids was 0.74% (1107 sites) for single nucleotide
      substitution and 0.24% for insertions (161 sites; 1388 bp) and deletions (189
      sites; 1393 bp). The IR regions have a lower rate of nucleotide substitution (3.5
      5.8-fold) and indels (4.3-7.1-fold) than single-copy regions. The intergenic
      spacers are the most divergent, and based on the length variation of the three
      intergenic spacers, 11 native Phalaenopsis orchids could be successfully
      distinguished. The coding genes, IR junction and RNA editing sites are relatively
      more conserved between the two moth orchids than between those of Phalaenopsis
      and Oncidium spp.

PMID- 22608521
TI  - The ethylene pathway contributes to root hair elongation induced by the
      beneficial bacteria Phyllobacterium brassicacearum STM196.
AB  - In Arabidopsis roots, some epidermal cells differentiate into root hair cells.
      Auxin regulates root hair positioning, while ethylene controls cell elongation.
      Phyllobacterium brassicacearum STM196, a beneficial strain of plant growth
      promoting rhizobacteria (PGPR) isolated from the roots of field-grown oilseed
      rape, stimulates root hair elongation in Arabidopsis thaliana seedlings. We
      investigated the role of ethylene in the response of root hair cells to STM196
      inoculation. While we could not detect a significant increase in ethylene
      biosynthesis, we could detect a slight activation of the ethylene signalling
      pathway. Consistent with this, an exhaustive survey of the root hair elongation
      response of mutants and transgenic lines affected in the ethylene pathway showed
      contrasting root hair sensitivities to STM196. We propose that local ethylene
      emission contributes to STM196-induceed root hair elongation.

PMID- 22608522
TI  - Getting a grasp on domain III/IV responsible for Auxin Response Factor-IAA
      protein interactions.
AB  - Auxin Response Factors (ARFs) and Indole Acetic Acid (IAA) proteins contain a
      similar carboxyl-terminal domain (domain III/IV) that facilitates interactions
      among these transcription factors as well as other proteins. The specificity of
      these interactions is controversial, and the mechanisms involved in these
      interactions have not been investigated. Here, we review some of the
      controversies about the specificities and requirements for ARF and IAA
      interactions and discuss some of the technical problems that might contribute to
      differences reported for these interactions. We make some preliminary conclusions
      that ARF activator-IAA, ARF activator-ARF activator, and ARF repressor-ARF
      repressor interactions are favored over ARF repressor-IAA and ARF repressor-ARF
      activator interactions, and we suggest that IAA-IAA interactions are largely
      indiscriminant. Based upon the predicted secondary structure of domain III/IV, we
      introduce a model for how ARF and IAA proteins might interact with one another
      through a ubiquitin-like beta-grasp fold.

PMID- 22608523
TI  - Differential contribution of individual dehydrin genes from Physcomitrella patens
      to salt and osmotic stress tolerance.
AB  - The moss Physcomitrella patens can withstand extreme environmental conditions
      including drought and salt stress. Tolerance to dehydration in mosses is thought
      to rely on efficient limitation of stress-induced cell damage and repair of cell
      injury upon stress relief. Dehydrin proteins (DHNs) are part of a conserved cell
      protecting mechanism in plants although their role in stress tolerance is not
      well understood. Four DHNs and two DHN-like proteins were identified in the
      predicted proteome of P. patens. Expression of PpDHNA and PpDHNB was induced by
      salt and osmotic stress and controlled by abscisic acid. Subcellular localization
      of the encoded proteins suggested that these dehydrins are localized in cytosol
      and accumulate near membranes during stress. Comparative analysis of dhnA and
      dhnB targeted knockout mutants of P. patens revealed that both genes play a role
      in cellular protection during salt and osmotic stress, although PpDHNA has a
      higher contribution to stress tolerance. Overexpression of PpDHNA and PpDHNB
      genes in transgenic Arabidopsis improved rosette and root growth in stress
      conditions, although PpDHNA was more efficient in this role. These results
      suggest that specific DHNs contribute considerably to the high stress tolerance
      of mosses and offer novel tools for genetic engineering stress tolerance of
      higher plants.

PMID- 22608524
TI  - Genes of phenylpropanoid pathway are activated in early response to Fusarium
      attack in flax plants.
AB  - Fusarium is the most common flax pathogen causing serious plant diseases and in
      most cases leading to plant death. To protect itself, the plant activates a
      number of genes and metabolic pathways, both to counteract the effects of the
      pathogen, and to eliminate the threat. The identification of the plant genes
      which respond to infection is the approach, that has been used in this study.
      Forty-seven flax genes have been identified by means of cDNA subtraction method
      as those, which respond to pathogen infection. Subtracted genes were classified
      into several classes and the prevalence of the genes involved in the broad
      spectrum of antioxidants biosynthesis has been noticed. By means of semi
      quantitative RT-PCR and metabolite profiling, the involvement of subtracted genes
      controlling phenylpropanoid pathway in flax upon infection was positively
      verified. We identified the key genes of the synthesis of these compounds. At the
      same time we determined the level of the metabolites produced in the
      phenylpropanoid pathway (flavonoids, phenolic acids) in early response to
      Fusarium attack by means of GC-MS technique. To the best of our knowledge this is
      the first report to describe genes and metabolites of early flax response to
      pathogens studied in a comprehensive way.

PMID- 22608525
TI  - OsIAA13-mediated auxin signaling is involved in lateral root initiation in rice.
AB  - The plant hormone auxin is essential for root formation. After auxin perception,
      transmission of the auxin signal progresses through the degradation of Aux/IAA
      proteins. In this study, we newly isolated and characterized a rice gain-of
      function mutant, Osiaa13, containing a single amino acid substitution in the core
      sequence required for the degradation of the OsIAA13 protein. The Osiaa13 mutant
      displayed typical auxin-related phenotypes: the number of lateral roots was
      significantly reduced and the root gravitropic response was defective. Osiaa13
      mutants also exhibited altered GUS staining controlled by the DR5 promoter in
      lateral root initiation sites. Furthermore, expression levels of several genes
      that might be associated with lateral root initiation were altered in Osiaa13.
      Taken together, our results indicate that OsIAA13 is involved in auxin signaling
      and controls the expression of genes that are required for lateral root
      initiation in rice.

PMID- 22608526
TI  - The determination of sulfite levels and its oxidation in plant leaves.
AB  - Sulfur is the sixth most abundant element in life and an important building block
      of proteins and cellular metabolites. Plants like bacteria can synthesize their
      sulfur-containing biomolecules from sulfate, where sulfite is an intermediate of
      the sulfur assimilation pathway. Above a certain threshold SO(2)/sulfite is
      cytotoxic and is rapidly metabolized to avoid damage. However, the existing data
      show considerable differences in basal sulfite levels both between species and
      apparent discrepancies in measured levels in the same species. In order to
      resolve this question we employed a sulfite detection method using chicken
      sulfite oxidase and developed an independent enzymatic assay, based on the
      specific detection of sulfite by sulfite reductase and compared those
      measurements to a modified colorimetric fuchsin-based method, specific for
      sulfite detection. We show here that when properly used the sulfite levels
      detected by the three methods can yield identical results. Furthermore, to
      examine the capacity of the plant to detoxify sulfite we injected sub-lethal
      sulfite solutions (yet, several folds higher than the basal levels) into
      Arabidopsis and tomato leaves and monitored the excess sulfite turnover. Within
      3h of sulfite injection, more than 80% of the injected sulfite in Arabidopsis and
      91% in tomato were oxidized to sulfate, demonstrating the high capacity of the
      sulfite oxidation mechanism/s in plants.

PMID- 22608527
TI  - Frequency of under- and overweight among children and adolescents during the
      economic transition in Poland.
AB  - The aim of this study is to examine the prevalence of underweight, overweight and
      obesity, using International Obesity Task Force (IOTF) criteria, in four cohorts
      of children and adolescents living in Poland in different economic eras:
      communist economy (1977/1978), crisis of the 1980s (1987/1988), political and
      economic transformation (1992/1994) and the free market economy (2002/2004).
      Analysis was conducted on a database including 10,934 records for children of the
      age 7-18 years. In Poland, in the last 26 years of economic and political
      transformations, the epidemic of obesity was not noticed but the growing
      incidence of children and adolescents with body mass deficit was observed
      (p<0.0001) (20.2% of girls in 2002/2004 vs. 11.0% in 1977/1978 and 12.1% of boys
      in 2002/2004 vs. 7.2% in 1977/1978). Lower parental education and a higher number
      of children in a family resulted in a higher prevalence of underweight (odds
      ratio [OR] fluctuated from 1.26 to 1.63). The social effects of the political
      transformation in Poland significantly affected families with low socio-economic
      status (SES), and especially more eco-sensitive boys. This result is opposite to
      the trends observed in Western countries and makes an important contribution to
      the current knowledge of the course of further changes in weight-to-height ratio
      at a global scale.

PMID- 22608528
TI  - The effects of diphenyl diselenide on oxidative stress biomarkers in Cyprinus
      carpio exposed to herbicide quinclorac (Facet(r)).
AB  - The occurrence of pollutants in the aquatic environment can produce severe toxic
      effects on non-target organisms, including fish. These sources of contamination
      are numerous and include herbicides, which represent a large group of toxic
      chemicals. Quinclorac, an herbicide widely applied in agriculture, induces
      oxidative stress due to free radical generation and changes in the antioxidant
      defense system. The aim of this study was to assess if dietary diphenyl
      diselenide (PhSe)2 has a protective effect in tissues of fish species Cyprinus
      carpio exposed to the quinclorac herbicide. The fish were fed with either a
      standard or a diet containing 3.0 mg/Kg of diphenyl diselenide for 60 d. After
      were exposed to 1 mg/L of Facet(r) (quinclorac commercial formulation) for 192 h.
      At the end of the experimental period, parameters as thiobarbituric acid-reactive
      substance levels (TBARS), protein carbonyl, catalase (CAT), superoxide dismutase
      (SOD), glutathione S-transferase (GST), nonprotein thiols (NPSH) and ascorbic
      acid in the liver, gills, brain and muscle were evaluated in Cyprinus carpio. In
      fish exposed to quinclorac and feeding with standard diet TBARS levels increased
      in liver and gills. However, SOD activity decreases in liver whereas no
      alterations were observed in catalase activity in this tissue. Quinclorac also
      decrease GST activity in liver and brain, NPSH in brain and muscle and ascorbic
      acid in muscle. Concerning protein carbonyl exposed to herbicide the fish did not
      show any alterations. The diphenyl diselenide supplemented diet reversed these
      effects, preventing increases in TBARS levels in liver and gills. GST activity
      was recovered to control values in liver. NPSH levels in brain and muscle
      increased remain near to control values. These results indicated that dietary
      diphenyl diselenide protects tissues against quinclorac induced oxidative stress
      ameliorating the antioxidant properties.

PMID- 22608529
TI  - Neutrophil number after interferon-alfa treatment is an independent predictive
      marker of overall survival in metastatic renal cell carcinoma.
AB  - BACKGROUND: The purpose of this study was to assess the outcome in patients
      treated by immunotherapy using interferon-alpha (IFN-alpha) and to evaluate the
      significance of the neutrophil count after IFN-alpha immunotherapy as a
      predictive marker for metastatic renal cell carcinoma (RCC). PATIENTS AND
      METHODS: We identified 84 patients with metastatic RCC who underwent
      immunotherapy with IFN-alpha between 1998 and 2006. The predictive values of the
      neutrophil count before and after IFN-alpha treatment as well as other clinical
      and laboratory parameters were assessed retrospectively. RESULTS: On univariate
      analysis, the significant correlation with overall survival (OS) was recognized
      in the Eastern Cooperative Oncology Group (ECOG) performance score (PS), lactate
      dehydrogenase (LDH) levels, corrected calcium levels, interval from diagnosis to
      treatment, and the ratio of neutrophil number before and after treatment with INF
      alpha. Multivariate analysis showed that ECOG PS, corrected calcium levels,
      interval from diagnosis to treatment and neutrophil number after IFN-alpha
      treatment were independent factors for OS. Using the number of neutrophils after
      IFN-alpha treatment, subgroups were identified using the Memorial Sloan-Kettering
      Cancer Center (MSKCC) model. The 1-year survival rate was 93% vs. 63% in the
      intermediate-risk group and 34% vs. 8% in the poor-risk group. In the favorable
      risk group, all patients had a good decrease in neutrophil number after treatment
      with IFN-alpha. CONCLUSION: Neutrophil number after IFN-alpha treatment can be a
      good predictive marker for OS in metastatic RCC. By combining MSKCC score with
      neutrophil number after treatment with IFN-alpha, we can subdivide each group.

PMID- 22608530
TI  - Glutathione S-transferase pi trapping method for generation and characterization
      of drug-protein adducts in human liver microsomes using liquid chromatography
      tandem mass spectrometry.
AB  - Covalent binding of reactive metabolites (RMs) to proteins is thought to play an
      important role in the processes leading to adverse drug reactions. Therefore,
      there is great interest in methodologies that enable the characterization of
      covalent binding of drugs to proteins. To facilitate the study of drug-protein
      adducts, we have developed a liquid chromatography-tandem mass spectrometry (LC
      MS/MS) method for characterizing RM-modified proteins formed through drug
      bioactivation in human liver microsomes (HLMs), which are commonly used for the
      in vitro drug bioactivation studies. The technique was illustrated by the
      trapping of RMs of acetaminophen (APAP) and raloxifene with human glutathione S
      transferase pi (hGSTP) as a model target protein. After hGSTP-supplemented HLM
      incubations, the modified/unmodified hGSTP fractions were collected by high
      performance liquid chromatography. hGSTP fractions were digested with trypsin,
      and then analyzed by linear ion trap-orbitrap mass spectrometry followed by a
      SEQUEST database search. Characteristic MS/MS fragment ions of RM-modified
      peptides were identified by searching for possible adducted-mass shifts. The
      method successfully revealed that RMs of both drugs adducted to Cys-47 of hGSTP
      and the mass shifts corresponded to modification by the N-acetyl-p-benzoquinone
      imine form of APAP and diquinone methide form of raloxifene, respectively. The
      developed method would be a possible tool for widespread use for the generation
      and characterization of drug-protein adducts in HLMs and has the potential to
      assess the risk of covalent binding of drugs to proteins.

PMID- 22608531
TI  - Different presentations and outcomes between HIV-infected and HIV-uninfected
      patients with Cryptococcal meningitis.
AB  - BACKGROUND AND PURPOSE: Cryptococcus species are the most common causative agents
      of fungal meningitis. Different populations may show different clinical
      manifestations and outcomes. In this retrospective study, we investigated these
      differences in patients with and without HIV infection. METHODS: From 1995 to
      2009, we collected data from HIV-infected or HIV-uninfected patients aged 18
      years or over who had cryptococcal meningitis (CM) in a medical center in Taiwan.
      We reviewed and analyzed their demographic data, clinical manifestations,
      therapeutic strategies and outcomes. RESULTS: Among the 72 patients with CM, 19
      HIV-infected patients were predominantly younger males, and all of them had AIDS
      status when CM was diagnosed. In contrast, the 53 HIV-uninfected patients were
      mostly older males with underlying diseases. The time from initial symptoms to
      diagnosis was shorter in HIV-infected patients (median 10 vs. 18 days, p =
      0.048). The HIV-infected patients presented with less pleocytosis (p = 0.003) and
      lower protein levels in the cerebrospinal fluid (CSF), but a higher proportion
      had positive results for cryptococci in the CSF (90% vs. 60%, p = 0.02) and blood
      (53% vs. 21%, p = 0.009) cultures. Surgical drains and repeated lumbar punctures
      for the management of increased intracranial pressure were performed in 47% of
      the HIV-infected patients and 38% of the HIV-uninfected patients. A lower
      mortality rate was observed in the HIV-infected patients (p = 0.038). On
      multivariate analysis, initial CD4 count <=20/mm(3) was an indicator of death or
      relapse in HIV-infected patients. In the HIV-uninfected group, the initial high
      cryptococcal antigen titer in the CSF (>=1:512) and hydrocephalus were related to
      unsatisfactory outcomes. CONCLUSION: In addition to well-known differences, we
      found a lower mortality in HIV-infected patients than in HIV-uninfected patients.
      Cryptococci and inflammation in the central nervous system may play important
      roles in the pathogenesis of CM. Low intensity of inflammation and effective
      surgical CSF drains for increased intracranial pressure and cryptococci removal
      may contribute to lower mortality in HIV-infected patients.

PMID- 22608532
TI  - O-GlcNAc regulates pluripotency and reprogramming by directly acting on core
      components of the pluripotency network.
AB  - O-linked-N-acetylglucosamine (O-GlcNAc) has emerged as a critical regulator of
      diverse cellular processes, but its role in embryonic stem cells (ESCs) and
      pluripotency has not been investigated. Here we show that O-GlcNAcylation
      directly regulates core components of the pluripotency network. Blocking O
      GlcNAcylation disrupts ESC self-renewal and reprogramming of somatic cells to
      induced pluripotent stem cells. The core reprogramming factors Oct4 and Sox2 are
      O-GlcNAcylated in ESCs, but the O-GlcNAc modification is rapidly removed upon
      differentiation. O-GlcNAc modification of threonine 228 in Oct4 regulates Oct4
      transcriptional activity and is important for inducing many pluripotency-related
      genes, including Klf2, Klf5, Nr5a2, Tbx3, and Tcl1. A T228A point mutation that
      eliminates this O-GlcNAc modification reduces the capacity of Oct4 to maintain
      ESC self-renewal and reprogram somatic cells. Overall, our study makes a direct
      connection between O-GlcNAcylation of key regulatory transcription factors and
      the activity of the pluripotency network.

PMID- 22608533
TI  - Is external memory memory? Biological memory and extended mind.
AB  - Clark and Chalmers (1998) claim that an external resource satisfying the
      following criteria counts as a memory: (1) the agent has constant access to the
      resource; (2) the information in the resource is directly available; (3)
      retrieved information is automatically endorsed; (4) information is stored as a
      consequence of past endorsement. Research on forgetting and metamemory shows that
      most of these criteria are not satisfied by biological memory, so they are
      inadequate. More psychologically realistic criteria generate a similar
      classification of standard putative external memories, but the criteria still do
      not capture the function of memory. An adequate account of memory function,
      compatible with its evolution and its roles in prospection and imagination,
      suggests that external memory performs a function not performed by biological
      memory systems. External memory is thus not memory. This has implications for:
      extended mind theorizing, ecological validity of memory research, the causal
      theory of memory.

PMID- 22608534
TI  - In vivo subcellular localization of Mal de Rio Cuarto virus (MRCV) non-structural
      proteins in insect cells reveals their putative functions.
AB  - The in vivo subcellular localization of Mal de Rio Cuarto virus (MRCV, Fijivirus,
      Reoviridae) non-structural proteins fused to GFP was analyzed by confocal
      microscopy. P5-1 showed a cytoplasmic vesicular-like distribution that was lost
      upon deleting its PDZ binding TKF motif, suggesting that P5-1 interacts with
      cellular PDZ proteins. P5-2 located at the nucleus and its nuclear import was
      affected by the deletion of its basic C-termini. P7-1 and P7-2 also entered the
      nucleus and therefore, along with P5-2, could function as regulators of host gene
      expression. P6 located in the cytoplasm and in perinuclear cloud-like inclusions,
      was driven to P9-1 viroplasm-like structures and co-localized with P7-2, P10 and
      alpha-tubulin, suggesting its involvement in viroplasm formation and viral
      intracellular movement. Finally, P9-2 was N-glycosylated and located at the
      plasma membrane in association with filopodia-like protrusions containing actin,
      suggesting a possible role in virus cell-to-cell movement and spread.

PMID- 22608535
TI  - Pheidippides redux: reducing risk for acute cardiac events during marathon
      running.
AB  - Prolonged strenuous exercise such as marathon running transiently increases the
      absolute and relative risk for sudden cardiac death. A 17-fold increase in the
      latter over resting baseline in previously sedentary middle-aged men is reduced
      due to cardioprotection from training in experienced marathon runners. Exertional
      rhabdomyolysis as a common occurrence during the race is accompanied by
      neutrophilia and elevated biomarkers of inflammation, including interleukin-6 and
      C-reactive protein. A hemostatic imbalance with prothrombotic effects includes in
      vivo platelet activation during the race. Suggesting a pathogenic role for these
      findings, plaque rupture due to atherothrombosis triggers acute exertional
      cardiac events, including sudden death, in low-risk runners as in high-risk
      patients such as those with diabetes mellitus. Strategies including prophylactic
      aspirin are considered to decrease the risk for acute cardiac events.

PMID- 22608536
TI  - Opalski syndrome: a variant of lateral-medullary syndrome.

PMID- 22608537
TI  - Hallucinations and aberrant perceptions are prevalent among the young healthy
      adult population.
AB  - INTRODUCTION: Hallucinations are frequent in clinical practice, with an incidence
      of up to 38.7% in the general population. We aim to determine the prevalence of
      hallucinations among healthy young adults in our environment. SUBJECTS AND
      METHODS: We designed an observational study, using as subjects 3rd to 6th year
      medical students at the Universidad Complutense de Madrid who complete clinical
      rotations in the Hospital Clinico San Carlos. After a screening questionnaire, an
      individual interview was conducted via telephone or e-mail to those students who
      reported hallucinations. We obtained clinical and epidemiological data through a
      semi-structured clinical interview performed by a third year neurology resident.
      RESULTS: N=134 (average age was 22.1 years; 77.6% were women). 74 respondents
      answered affirmatively to one or more screening questions, and 54 completed the
      follow-up interview. 22.2% described visual phenomena and 64.8%, auditory. The
      majority reported sleep-related experiences and auditory perceptions related to
      hyper vigilance, such as hearing the telephone or the doorbell ring when in fact
      it had not (38.8%). All subjects had good insight into their experiences and none
      had psychotic symptoms. Two cases were associated with substance abuse.
      CONCLUSIONS: Hallucinations are frequent among the general population.
      Traditionally, auditory phenomena have been associated with psychotic pathology,
      and other studies show a low population incidence (0.6%). However, in our sample,
      short auditory perceptions with immediate analysis were frequent and not
      pathological.

PMID- 22608539
TI  - Subdural haematoma secondary to epidural anesthesia. A rare complication.

PMID- 22608538
TI  - Validation of a short useful questionnaire in Spanish for the epidemiological
      screening of epilepsy in Spain. EPIBERIA Questionnaire.
AB  - INTRODUCTION: There is a major gap in knowledge about the epidemiology of
      epilepsy in Mediterranean countries. The EPIBERIA group was formed with the aim
      of promoting the conducting of epidemiological studies in this region in order to
      improve this situation. This paper deals with the validation of a brief
      questionnaire for screening patients with epilepsy in the general population.
      METHODS: We selected an English-language questionnaire previously validated by
      the Ottman group. It was translated, modified to suit the characteristics of the
      Spanish population, and administered to a sample of 200 patients (93 epileptics
      and 107 non-epileptic patient controls) sampled consecutively from 5 epilepsy
      units in different cities in Spain. Both groups were homogeneous in demographic
      variables and the control group was representative of the general population.
      RESULTS: We obtained a sensitivity of 100% and a specificity of 74.77% for the
      least rigorous correction model for the questionnaire, with a sensitivity of
      94.62% and a specificity of 99.07% for the most stringent correction model. The
      PPV ranged from 7.48% for the first case to 69.49% in the second, assuming an
      epilepsy prevalence of 2%. CONCLUSIONS: The questionnaire EPIBERIA is a valid
      Spanish tool for epilepsy screening in the general population in Spain.

PMID- 22608540
TI  - Neurological focal signs as a first manifestation of cardiac myxoma.

PMID- 22608541
TI  - Health-related quality of life for men with prostate cancer--an evaluation of
      outcomes 12-24 months after treatment.
AB  - OBJECTIVE: To determine the health-related quality of life (HRQoL) impact of
      prostate cancer interventions at 2 years post-treatment, and between the 12- and
      24-month interval, to better characterize this measure. MATERIALS AND METHODS:
      Patients treated at the Center for Prostate Disease Research between June 2003
      and February 2010 were offered enrollment into a HRQoL study that entailed a
      baseline evaluation before prostate biopsy and at 3, 6, 9, 12, 18, 24, and 30
      months thereafter. The instruments used were the Expanded Prostate Cancer Index
      Composite (EPIC), EPIC Demographic, and Medical Outcomes Study Short-Form 36 (SF
      36). A Student's t-test and ANOVA were used to examine the association between
      HRQoL scores, patient demographic, and disease features. Multivariable regression
      models were used to analyze change over time. Estimates of risk, corresponding
      confidence intervals, and P values are presented for these longitudinal findings.
      RESULTS: The study group was comprised of 595 patients. African Americans (AA)
      had slightly lower baseline raw scores in all EPIC and SF-36 HRQoL domains, but
      on bivariate analysis, there was no statistical difference in change of scores
      over time. Radical prostatectomy (RP) led to the greatest decline in urinary
      function. Bowel function significantly worsened with the addition of hormone
      therapy (HT) to external beam radiation therapy (EBRT). Sexual bother and
      function had a marked decline in all active treatment options. Despite these
      changes, there were no differences in overall satisfaction. SF-36 domains were
      not affected by RP, whereas EBRT and EBRT + HT had universal impact. For the 12-
      to 24-month interval, specifically, patients who underwent EBRT fared worse over
      this time period, showing continued worsening of urinary bother, hormonal
      function, physical role, physical component summary, and overall satisfaction.
      Patients who underwent RP did not show any further decline in the 12- to 24-month
      interval, but instead showed improvement. CONCLUSIONS: Because of the protracted
      nature of recovery after surgery, delayed onset of effects from radiation,
      potential interval decline secondary to age-related symptoms, and longevity of
      patients with prostate cancer, determination of long-term HRQoL outcomes is
      integral. Counseling with regard to these outcomes should be balanced with
      oncologic expectations from treatment.

PMID- 22608542
TI  - Contrasted effects of the multitarget TKi vandetanib on docetaxel-sensitive and
      docetaxel-resistant prostate cancer cell lines.
AB  - OBJECTIVES: Overexpression of epidermal growth factor receptor (EGFR) and
      angiogenic factors is associated with the progression of androgen-independent
      prostate cancer (AIPC). We examined the effects of vandetanib, an inhibitor of
      vascular endothelial growth factor (VEGFR), EGFR, and rearranged during
      transfection (RET) tyrosine-kinase activities, alone or combined with docetaxel,
      on PC3 docetaxel-sensitive (PC3wt) or docetaxel-resistant (PC3R) AIPC cell growth
      in vivo and in vitro. METHODS: Mice bearing PC3wt or PC3R tumors were treated for
      3 weeks with vandetanib (25 or 50 mg/kg/d p.o., 5 d/wk), docetaxel (10 or 30
      mg/kg i.p., 1 d/wk), or their combination (low or high doses). Xenograft tumors
      were analyzed for expression of Ki-67, EGFR, VEGFR2, and production of VEGFA.
      RESULTS: On PC3wt, vandetanib at both doses stimulated tumor growth, whereas
      docetaxel at both doses exerted strong growth-inhibiting effects. The low-dose
      vandetanib-docetaxel combination resulted in tumor growth similar to that of
      control, whereas the high-dose combination induced a significant
      antiproliferative effect. In contrast, on PC3R, the low-dose of vandetanib had no
      effect on tumor growth, whereas the high-dose of vandetanib significantly
      inhibited tumor growth. Docetaxel at both doses exerted moderate and transient
      antitumor effects. The combination of high-dose vandetanib with high-dose
      docetaxel resulted in antiproliferative effects, which were lower than expected
      from the sum of individual drug effects. Importantly, tumor analyses revealed
      overexpression of the EGFR/VEGFR pathways in PC3R relative to PC3wt. CONCLUSION:
      Present results suggest that vandetanib should not be associated with docetaxel
      in treatment-naive or docetaxel-resistant prostate cancer (CaP). The use of high
      dose vandetanib alone may warrant further investigation in patients with
      docetaxel-resistant AIPC overexpressing VEGFR/EGFR pathways.

PMID- 22608543
TI  - Variant (divergent) histologic differentiation in urothelial carcinoma is under
      recognized in community practice: impact of mandatory central pathology review at
      a large referral hospital.
AB  - BACKGROUND AND OBJECTIVE: Urothelial carcinoma (UC) demonstrating variant
      histologic differentiation is associated with poor outcomes, and certain variants
      exhibit differing therapeutic responses compared with pure conventional UC.
      Little is known about the awareness and reporting practices of UC with variant
      histology in community practice. MATERIALS AND METHODS: Patients diagnosed with
      UC based on an outside pathologic review had their pathology centrally reviewed
      before instituting therapy. A discordant diagnosis was defined as the presence of
      variant histologic differentiation not reported by the referring institution.
      Variant histologic differentiation was quantitated as focal (10%-50%) or
      extensive (>50%). RESULTS: Of 589 transurethral biopsies (TURBTs), 115 (19.5%)
      UCs demonstrated variant histologic differentiation. Muscle invasion at TURBT and
      extravesical disease at cystectomy was present in 69% and 52%, respectively. Of
      56 patients with at least 1 year follow-up, recurrence-free survival was 56%. The
      majority (90%) showed a single variant histology, which was extensive in 58% of
      cases. Squamous differentiation (32%) was the most common variant histology
      identified, followed by small cell (16%), glandular (13%), micropapillary (12%),
      nested (8%), sarcomatoid (6%), lymphoepithelial (3%), and plasmacytoid (1%) type.
      Variant histologic differentiation was not documented by the referring
      institution in 44% of cases, of which 47% were extensive. Commonly under
      recognized patterns included lymphoepithelial (2) and plasmacytoid (1) types
      (100%), nested (7, 87%), micropapillary (10, 83%), and small cell (7, 44%).
      CONCLUSIONS: This study emphasizes the importance of central pathology review in
      the management of bladder cancer patients and the need for increased awareness of
      this relatively common phenomenon in UC.

PMID- 22608545
TI  - Extracorporeal shockwave therapy shows time-dependent chondroprotective effects
      in osteoarthritis of the knee in rats.
AB  - BACKGROUND: Recent studies reported that extracorporeal shockwave therapy (ESWT)
      has a chondroprotective effect on the initiation and regression of osteoarthritis
      of the knee in rats. However, the time course effects of ESWT in the
      osteoarthritic knee are not fully understood. The purpose of this study was to
      evaluate the effects of ESWT over time on osteoarthritis of the knee in rats.
      METHODS: We used 72 8-week-old male Sprague-Dawley rats with body weights ranging
      from 245 to 265 g. We randomly divided the rats into three groups, with 24 rats
      in each group. The control group received neither surgery nor ESWT. The anterior
      cruciate ligament transected (ACLT) group underwent anterior cruciate ligament
      transection but received no ESWT. The ACLT plus ESWT group underwent ACL
      transection and received ESWT at 1 wk after surgery. The animals were killed at
      2, 4, 8, and 12 wk, 6 rats from each group at each time course. Evaluation
      parameters included Mankin score, Safranin O stain, and collagen II for the
      articular cartilage; and vascular endothelial growth factor (VEGF), bone
      morphogenetic-2 (BMP-2), and osteocalcin for the subchondral bone using
      histopathological examination and immunohistochemical analysis. RESULTS: The ACLT
      group showed significant increases in Mankin score and Safranin O stain, and a
      decrease in collagen II in the articular cartilage, and significant decreases in
      VEGF, BMP-2, and osteocalcin in the subchondral bone compared with the control (P
      < .05). The ACLT + ESWT group showed significant decreases in Mankin score and
      Safranin O stain and an increase in collagen II in the articular cartilage, and
      significant increases in VEGF, BMP-2, and osteocalcin in the subchondral bone
      compared with the control group. The changes in the ACLT + ESWT group appeared to
      correlate with the time courses of treatment; the most beneficial effects were
      noticed 4 weeks after ESWT. CONCLUSION: Extracorporeal shockwave therapy is
      effective in preventing osteoarthritis of the knee in rats. The beneficial
      effects of ESWT appear to be time-dependent beginning at 4 weeks after treatment.

PMID- 22608544
TI  - Clinical outcome in patients receiving systemic therapy for metastatic
      sarcomatoid renal cell carcinoma: a retrospective analysis.
AB  - OBJECTIVES: Sarcomatoid metastatic renal cell carcinoma (mRCC) represents an
      aggressive subset of disease, and a definitive therapeutic strategy is lacking.
      We seek to define outcomes associated with systemic therapy (including
      immunotherapy, cytotoxic therapy, and targeted agents) for sarcomatoid mRCC, with
      attention to novel prognostic schema. MATERIALS AND METHODS: From an
      institutional database including 270 patients with mRCC, we identified 34
      patients with documented sarcomatoid features. Within this cohort, we assessed 21
      patients who received systemic therapy. Survival was assessed in the overall
      cohort and in subgroups divided by clinicopathologic characteristics, including
      the extent of sarcomatoid features, Memorial Sloan-Kettering Cancer Center
      (MSKCC) risk criteria, Heng criteria, and the nature of systemic therapy
      rendered. RESULTS: Of the 21 patients assessed, 2 patients received chemotherapy,
      7 patients received immunotherapy, and 12 patients received targeted agents as
      their first line treatment. Median overall survival (OS) in the overall cohort
      was 18.0 months (95% CI 6.9-22.0). By MSKCC criteria, patients with poor-risk
      disease had a median OS of 4.7 months, compared with 20.1 months for patients
      with intermediate-risk disease [hazard ratio (HR) 0.02, 95%CI 0.003-0.15; P =
      0.0001]. A similar difference in median OS was seen poor- and intermediate-risk
      groups when stratifying by Heng criteria (HR 0.17, 95%CI 0.001-0.12). There was
      no significant difference in survival in patients with sarcomatoid predominant
      disease vs. nonpredominant disease (HR 0.62, 95%CI 0.23-1.65; P = 0.34), nor was
      there a difference amongst patients who received targeted therapies vs.
      nontargeted therapies (HR 1.0, 95%CI 0.61-1.40; P = 0.36). CONCLUSIONS: Compared
      with previous series and prospective trials assessing patients with sarcomatoid
      mRCC, the observed survival was prolonged. Although both Heng and MSKCC risk
      scores may be useful in determining prognosis, further studies are needed to
      identify relevant biomarkers and define the optimal therapeutic strategy for this
      disease.

PMID- 22608547
TI  - Gut to artery to ureter--robbing Peter to pay Paul.

PMID- 22608546
TI  - Magnesium deficiency promotes secretion of high-mobility group box 1 protein from
      lipopolysaccharide-activated macrophages in vitro.
AB  - BACKGROUND: High-mobility group box 1 (HMGB1) is a critical mediator of sepsis
      that is closely related to sepsis lethality. Magnesium deficiency predisposes to
      worse outcomes from endotoxin challenge by promoting the production of cytokines.
      However, whether magnesium deficiency affects the expression and release of HMGB1
      is not currently known. In the present study, we explored the effect of magnesium
      deficiency on the expression and secretion of HMGB1 in lipopolysaccharide (LPS)
      activated RAW264.7 macrophages. METHODS: RAW264.7 cells were incubated with LPS
      in normal magnesium (1 mmol/L magnesium sulfate) or low magnesium (0.1 mmol/L
      magnesium sulfate) in Roswell Park Memorial Institute 1640 medium. An enzyme
      linked immunosorbent assay was used to detect HMGB1 levels in the culture
      supernatant. Real-time polymerase chain reaction was used to assess the HMGB1
      mRNA levels. A nuclear/cytoplasm extraction kit was used to extract the nuclear
      and cytoplasmic proteins. Western blotting was used to observe the changes in
      translocation of HMGB1 from the nucleus to the cytoplasm. A nuclear factor kappa
      light chain enhancer of activated B cells (NF-kappaB) p50/p65 transcription
      factor assay kit was used to analyze the NF-kappaB activity in nuclear extracts.
      RESULTS: Magnesium deficiency promoted translocation of HMGB1 from the nucleus to
      the cytoplasm and its extracellular secretion in LPS-activated macrophages, while
      enhancing the expression of HMGB1 mRNA. Furthermore, magnesium deficiency
      promoted the translocation of NF-kappaB from the cytoplasm to the nucleus in LPS
      activated macrophages. CONCLUSIONS: Magnesium deficiency promotes the
      translocation of HMGB1 from the nucleus to the cytoplasm and the expression of
      HMGB1 mRNA. Magnesium deficiency also activates the NF-kappaB signaling pathway.

PMID- 22608548
TI  - High and abnormal forms of aggression in rats with extremes in trait anxiety-
      involvement of the dopamine system in the nucleus accumbens.
AB  - A better neurobiological understanding of high and abnormal aggression based on
      adequate animal models is essential for novel therapy and prevention. Selective
      breeding of rats for extremes in anxiety-related behavior resulted in two
      behavioral phenotypes with high and abnormal forms of aggression. Rats bred for
      low anxiety-related behavior (LAB) consistently show highest levels of aggression
      and little social investigation in the resident-intruder (RI) test, compared with
      non-selected low-aggressive (NAB) rats. High anxiety-related (HAB) rats also show
      higher levels of aggression than NAB rats, but to a lesser extent than LAB rats.
      Accordingly, extremes in inborn anxiety in both directions are linked to an
      increased aggression level. Further, both LAB and HAB, but not NAB males, display
      abnormal aggression (attacks towards vulnerable body parts, females or narcotized
      males), which is particularly prominent in LABs. Also, only in LAB rats, the
      nucleus accumbens (NAc) was found to be strongly activated in response to the RI
      test as reflected by increased c-fos and zif268 mRNA expression, and higher local
      dopamine release compared with NAB males, without differences in local dopamine
      receptor binding. Consequently, local pharmacological manipulation by infusion of
      an anesthetic (lidocaine, 20 MUg/MUl) or a dopamine D2 (haloperidol, 10 ng/MUl),
      but not D1 (SCH-23390 10 ng/MUl), receptor antagonist significantly reduced high
      aggression in LAB rats. Thus, LAB rats are an adequate model to study high and
      abnormal aggression. In LAB males, this is likely to be linked to hyper
      activation of the reward system, as found in psychopathic patients. Specifically,
      activation of the accumbal dopamine system is likely to underlie the high
      aggression observed in LAB rats.

PMID- 22608549
TI  - Microorganisms in landfill bioreactors for accelerated stabilization of solid
      wastes.
AB  - Landfill bioreactors (LBRs) with management of leachate and biogas have presented
      numerous advantages such as accelerated stabilization of solid wastes, reduced
      amount of leachate, and in situ leachate treatment. Such advantages have
      minimized environmental risks, have allowed extension of the useful life of the
      landfill site, and have fostered cost reduction. LBRs of three types have been
      developed using both anaerobic and aerobic modes: anaerobic, aerobic, and hybrid.
      Microorganisms in landfills cause various reactions related with organic
      fractions and heavy metals. Such functions have been stimulated in LBRs by
      recirculation of leachate with or without aeration. To date, most studies of
      microorganisms in LBRs have analyzed bacteria and archaea based on 16S rRNA genes
      and have analyzed fungi based on 18S rRNA genes from a taxonomical viewpoint.
      Indicator genes for specific functions in LBRs such as nitrification,
      denitrification, and methane production have also been monitored. The population
      dynamics of microorganisms in LBRs have been partially clarified, but the
      obtained data remain limited because of highly heterogeneous features of solid
      wastes inside LBRs. Systematic monitoring of microorganisms should be established
      to improve LBR performance.

PMID- 22608550
TI  - Increased transcription of NOP15, involved in ribosome biogenesis in
      Saccharomyces cerevisiae, enhances the production yield of RNA as a source of
      nucleotide seasoning.
AB  - Yeast RNA is a good source of nucleotide seasoning, and more than half of yeast
      RNA consists of ribosomal RNA (rRNA). Previously, we reported the development of
      a Saccharomyces cerevisiae strain displaying a 1.4- to 2.3-times higher RNA
      content than the wild-type strain through the isolation of dominant suppressors
      (designated SupA to SupG strains) from a Deltarrn10 disruptant showing decreased
      rRNA transcription. In the present study, the cloning of one of the genes
      responsible for the suppression was attempted using a genomic library from the
      SupD strain. NOP15, a gene involved in ribosome biogenesis, was found to be
      responsible for suppressing the growth defect of the Deltarrn10 disruptant. The
      isolated NOP15 allele (designated NOP15(T-279C)) possessed a single T to C
      substitution at nucleotide position-279 of NOP15. The transcription level of
      NOP15(T-279C) in the originally isolated SupD strain was 2-fold higher than that
      in the Deltarrn10 disruptant. Furthermore, a dose-dependent relationship between
      the transcription level of NOP15 and total amount of RNA in the Deltarrn10
      disruptant was observed: the enhanced transcription due to the NOP15(T-279C)
      allele is involved in the suppression mechanisms in the SupD strain. Introduction
      of the NOP15(T-279C) allele into the wild-type strain increased the total RNA
      content by 1.4-fold. These results indicate that the transcription level of NOP15
      is an important determinant of the productivity of RNA and that its increased
      transcription provides an effective approach to obtain higher RNA yields in
      yeast.

PMID- 22608551
TI  - Indolepyruvate ferredoxin oxidoreductase: An oxygen-sensitive iron-sulfur enzyme
      from the hyperthermophilic archaeon Thermococcus profundus.
AB  - Thermococcus profundus is a strictly anaerobic sulfur-dependent archaeon that
      grows optimally at 80 degrees C by peptide fermentation. Indolepyruvate
      ferredoxin oxidoreductase (IOR), an enzyme involved in the peptide fermentation
      pathway, was purified to homogeneity from the archaeon under strictly anaerobic
      conditions. The maximal activity was obtained above the boiling temperature of
      water (105 degrees C), with a half-life of 62min at 100 degrees C and 20min at
      105 degrees C. IOR was oxygen-sensitive with a half-life of 7h at 25 degrees C
      under aerobic conditions. The specific activity of T. profundus IOR was found to
      be dependent on the number of [4Fe-4S] clusters in the enzyme.

PMID- 22608552
TI  - De novo sequencing and analysis of the termite mushroom (Termitomyces
      albuminosus) transcriptome to discover putative genes involved in bioactive
      component biosynthesis.
AB  - A one-eighth 454 sequencing run produced 82,386 high-quality reads. De novo
      assembly generated 6494 unique sequences. Based on the bioinformatic analysis, we
      found many the known enzymes involved in the biosynthesis of triterpene saponin
      in Termitomyces albuminosus, including 6 cytochrome P450 and 22
      glycosyltransferase unique genes.

PMID- 22608553
TI  - Preferential emergence of cell types expressing markers for primitive endoderm
      lineages in mouse embryonic stem cells expressing exogenous EGAM1 homeoprotein.
AB  - Embryonic stem (ES) cells have been considered as a valuable renewable source of
      materials in regenerative medicine. Recently, we identified the homeoprotein
      EGAM1 both in preimplantation mouse embryos and mouse ES cells. Expression of the
      Egam1 transcript and its encoded protein was detectable in differentiating mouse
      ES cells, while it was almost undetectable in undifferentiated cells. In the
      present study, in order to clarify the effect of forced expression of EGAM1 on
      the differentiation of mouse ES cells in vitro, transfectants expressing
      exogenous EGAM1 were generated. Egam1 transfectants promoted differentiation into
      cell types expressing Gata6, Gata4, Afp, or Plat, genes associated with emergence
      of the extra-embryonic endoderm lineages. On the other hand, Egam1 transfectants
      inhibited the expression of specific genes for the embryonic lineages, including
      Fgf5 (epiblast) and T (mesoderm), in addition to Cdx2, a specific gene for the
      extra-embryonic trophectoderm lineages. Changes in the percentage of cells
      recognizing by antibodies against specific marker proteins closely correlated
      with the expression patterns of their transcripts. Taken together, the results
      obtained in this study suggested that mouse ES cells expressing exogenous EGAM1
      preferentially differentiate into extra-embryonic primitive endoderm lineages,
      rather than embryonic lineages or extra-embryonic trophectoderm lineages.

PMID- 22608554
TI  - Application of computational fluid dynamics in tissue engineering.
AB  - The process of tissue regeneration consists of a set of complex phenomena such as
      hydrodynamics, nutrient transfer, cell growth, and matrix deposition. Traditional
      cell culture and bioreactor design procedure follow trial-and-error analyses to
      understand the effects of varying physical, chemical, and mechanical parameters
      that govern the process of tissue regeneration. This trend has been changing as
      computational fluid dynamics (CFD) analysis can now be used to understand the
      effects of flow, cell proliferation, and consumption kinetics on the dynamics
      involved with in vitro tissue regeneration. Furthermore, CFD analyses enable
      understanding the influence of nutrient transport on cell growth and the effect
      of cell proliferation as the tissue regenerates. This is especially advantageous
      in improving and optimizing the design of bioreactors and tissue culture.
      Influence of parameters such as velocity, oxygen tension, stress, and strain on
      tissue growth can be effectively studied throughout the bioreactor using CFD as
      it becomes impractical and cumbersome to install probes at several locations in
      the bioreactor. Hence, CFD offers several advantages for the advancement of
      tissue engineering.

PMID- 22608555
TI  - Catalytic removal of acetaldehyde in saliva by a Gluconobacter strain.
AB  - Acetaldehyde (AA) accumulates in the oral cavity after alcohol intake and is
      responsible for an increased risk of alcohol-related upper aerodigestive tract
      (UDAT) cancer among aldehyde dehydrogenase 2-inactive heterozygotes in
      particular. Thus, the removal of AA from the saliva to a level below its
      mutagenic concentration (50 MUM) after drinking is a potentially straightforward
      method for reducing the risk of alcohol-related UDAT cancer. Although microbial
      cells with AA-decomposing activity could potentially serve as a useful agent for
      the catalytic removal of AA from the saliva without the supplemental addition of
      cofactors, these cells generally exhibit strong AA-producing activity from
      ethanol, which is present in excess (50mM) over AA (100 MUM) in the saliva after
      drinking. In this study, we observed that Gluconobacter kondonii (GK) cells
      efficiently decomposed salivary AA (100-390 MUM) without the supplemental
      addition of cofactors irrespective of the type of alcoholic beverages consumed,
      even in the presence of an excess of ethanol (63 mM). Hydrogen peroxide, which is
      carcinogenic in animal experiments, was not produced because of the AA removal.
      The GK cells incubated at 45  degrees C and pH 3.5 for 15 h were killed, but they
      retained 80% of their original AA-decomposing activity. The treated cells were
      used as nonviable microcapsules that harbor a membrane-bound AA-decomposing
      activity.

PMID- 22608556
TI  - Synaptic plasticity regulated by protein-protein interactions and
      posttranslational modifications.
AB  - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate
      receptors (AMPARs) mediate the majority of fast excitatory synaptic transmission
      in the brain. AMPARs dynamically cycle in and out of the postsynaptic membrane in
      an activity-dependent manner. Because the number and functional properties of
      AMPARs at the postsynapse determine the efficacy of synaptic transmission,
      molecular mechanisms underlying AMPAR trafficking and gating are considered to
      have a central role in synaptic plasticity, a basic mechanism for learning and
      memory. In this chapter, we review the current knowledge about the regulatory
      mechanisms for AMPAR trafficking and channel gating by protein-protein
      interactions and posttranslational modifications. Especially, we focus on the
      recently established mode of action of the AMPAR auxiliary subunit,
      stargazin/TARPs, and PSD-95 scaffold. Furthermore, we introduce novel players in
      AMPAR regulation, PSD-95 palmitoylating enzymes and epilepsy-related ligand,
      LGI1.

PMID- 22608557
TI  - Potential use of G protein-coupled receptor-blocking monoclonal antibodies as
      therapeutic agents for cancers.
AB  - The therapeutic use of monoclonal antibodies (mAbs) is the fastest growing area
      of pharmaceutical development and has enjoyed significant clinical success since
      approval of the first mAb drug in1984. However, despite significant effort, there
      are still no approved therapeutic mAbs directed against the largest and most
      attractive family of drug targets: G protein-coupled receptors (GPCRs). GPCRs
      regulate essentially all cellular processes, including those that are fundamental
      to cancer pathology, such as proliferation, survival/drug resistance, migration,
      differentiation, tissue invasion, and angiogenesis. Many different GPCR isoforms
      are enhanced or dysregulated in multiple tumor types, and several GPCRs have
      known oncogenic activity. With approximately 350 distinct GPCRs in the genome,
      these receptors provide a rich landscape for the design of effective, targeted
      therapies for cancer, a uniquely heterogeneous disease family. While the
      generation of selective, efficacious mAbs has been problematic for these
      structurally complex integral membrane proteins, progress in the development of
      immunotherapeutics has been made by several independent groups. This chapter
      provides an overview of the roles of GPCRs in cancer and describes the current
      state of the art of GPCR-targeted mAb drugs.

PMID- 22608558
TI  - Fibroblast activation protein-alpha: a key modulator of the microenvironment in
      multiple pathologies.
AB  - Fibroblast activation protein-alpha (FAP) is a serine protease that can provide
      target specificity to therapeutic agents because in adults its expression is
      restricted to pathologic sites, including cancer, fibrosis, arthritis, wounding,
      or inflammation. It is not expressed in most normal tissues. The majority of FAP
      is expressed by activated fibroblasts responding to the pathologic situations.
      FAP is typically found as a type II transmembrane protein physically attached to
      cells and with the bulk of the protein, including the catalytic domain, exposed
      to the extracellular space and accessible to small molecules. In this chapter, we
      review the structure, substrate specificities, signaling functions, and current
      design of FAP inhibitors. Evidence indicating the presence of FAP in multiple
      cancers, arthritis, fibrosis, keloids, and other pathologies is described and
      indicates possible roles for FAP in facilitating cell invasion and growth.
      Separate sections are devoted to the role of FAP in coordinating the stromal
      response to cancer, including a role in angiogenesis and a potential role in
      modulation of the antitumor immune response. Finally studies attempting to
      demonstrate the clinical potential of FAP are discussed, as well as some novel
      applications employing FAP in therapy or diagnosis. Throughout this review,
      effort is made to highlight areas where information is lacking and to highlight
      important questions that require further investigation.

PMID- 22608559
TI  - Barx homeobox family in muscle development and regeneration.
AB  - Homeobox transcription factors are key intrinsic regulators of myogenesis. In
      studies spanning several years, we have characterized the homeobox factor Barx2
      as a novel marker for muscle progenitor cells and an important regulator of
      muscle growth and repair. In this review, we place the expression and function of
      Barx2 and its paralogue Barx1 in context with other muscle-expressed homeobox
      factors in both embryonic and adult myogenesis. We also describe the structure
      and regulation of Barx genes and possible gene/disease associations. The
      functional domains of Barx proteins, their molecular interactions, and cellular
      functions are presented with particular emphasis on control of genes and
      processes involved in myogenic differentiation. Finally, we describe the patterns
      of Barx gene expression in vivo and the phenotypes of various Barx gene
      perturbation models including null mice. We focus on the Barx2 null mouse model,
      which has demonstrated the critical roles of Barx2 in postnatal myogenesis
      including muscle maintenance during aging, and regeneration of acute and chronic
      muscle injury.

PMID- 22608560
TI  - Role of adrenomedullin in the growth and differentiation of stem and progenitor
      cells.
AB  - Stem cells have captured the imagination of the general public by their potential
      as new therapeutic tools in the fight against degenerative diseases. This
      potential is based on their capability for self-renewal and at the same time for
      producing progenitor cells that will eventually provide the building blocks for
      tissue and organ regeneration. These processes are carefully orchestrated in the
      organism by means of a series of molecular cues. An emerging molecule which is
      responsible for some of these physiological responses is adrenomedullin, a 52
      amino acid regulatory peptide which increases proliferation and regulates cell
      fate of stem cells of different origins. Adrenomedullin binds to specific
      membrane receptors in stem cells and induces several intracellular pathways such
      as those involving cAMP, Akt, or MAPK. Regulation of adrenomedullin levels may
      help in directing the growth and differentiation of stem cells for applications
      (e.g., cell therapy) both in vitro and in vivo.

PMID- 22608561
TI  - Cell-cycle control in oocytes and during early embryonic cleavage cycles in
      ascidians.
AB  - The completely transparent eggs and embryos of the ascidian Phallusia mammillata
      are well suited for imaging-based studies of how cell cycle control mechanisms
      have been integrated into the processes of meiosis, fertilization, and embryonic
      development. Several cell cycle-related issues that pertain to reproduction and
      development have been addressed using the ascidian model. For example, how are
      sperm-triggered calcium oscillations controlled by cell cycle kinases? How is
      chromosome segregation during meiosis regulated? What processes does the Mos/MAPK
      signaling cascade control in eggs in addition to CSF-mediated cell cycle arrest?
      Following fertilization ascidians blastomeres display cell cycle asynchrony,
      oriented cell division, and unequal cleavage resulting in the formation of a
      distinctive gastrula composed of precisely 112 cells. Here, we shall summarize
      these topics and where possible show how the mechanisms identified in ascidians
      compare to those identified in other organisms.

PMID- 22608562
TI  - Role of major sperm protein (MSP) in the protrusion and retraction of Ascaris
      sperm.
AB  - Nematode sperm offer a unique perspective for investigating amoeboid cell
      motility. These cells display the hallmark features of amoeboid movement but
      power their locomotion with a cytoskeleton composed of major sperm protein (MSP)
      filaments in place of the familiar actin cytoskeleton found in other crawling
      cells. Thus, properties of sperm can be compared to those of actin-rich cells to
      identify the shared features that are essential to motility. Sperm are simple
      cells in which cytoskeletal dynamics are tightly coupled to protrusion of the
      leading edge and retraction of the cell body. These features have facilitated
      reconstitution of both protrusion and retraction in cell-free extracts and
      enabled identification of accessory components in the motility apparatus as well
      as elucidation of the mechanical basis of movement. Six MSP accessory proteins
      have been isolated including four components of the sperm cytoskeleton and two
      enzymes that play key roles in regulating cytoskeletal dynamics and locomotion.
      Analysis of this versatile in vitro motility system has identified motor
      independent mechanisms for protrusion and retraction that are based on changes in
      filament-packing density. These changes result in expansion and contraction of
      the MSP-filament network that generate the forces for movement. We discuss how
      the mechanisms of motility that operate in nematode sperm may contribute
      generally to the movement of crawling cells.

PMID- 22608564
TI  - New insights into the regulation of sexual reproduction in Closterium.
AB  - The genus Closterium, which is the closest unicellular relative to land plants,
      is the best-characterized charophycean green alga with respect to the process of
      sexual reproduction. In two representative heterothallic species, the steps and
      methods of intercellular communication were fully described. Glycoproteinaceous
      sex pheromones involved in the progress of these processes were physiologically
      and biochemically characterized and the corresponding genes were cloned. These
      pheromones function in most steps of sexual reproduction. For elucidating the
      mechanisms of sexual reproduction in detail, molecular tools such as expressed
      sequence tag, microarray analysis, and genetic transformation systems have been
      established, and whole genome analyses are ongoing. Finally, sexual reproductive
      isolation among mating groups was characterized, and the mechanism involved in
      this isolation was considered with respect to sex pheromones. In homothallic
      Closterium, the presence of a pheromone orthologous to the heterothallic type and
      possible sexual differentiation were also described, through the combination of
      closely related heterothallic cells.

PMID- 22608563
TI  - Role of endoglin in fibrosis and scleroderma.
AB  - Fibrosis plays a role in many pathological conditions, among which is the
      autoimmune disease systemic sclerosis (SSc). SSc is characterized by fibrosis in
      the skin and internal organs, but the etiology remains to be elucidated.
      Transforming growth factor-beta (TGF-beta) is a key player in the fibrotic
      process, also in SSc. TGF-beta induces the production of several components of
      the extracellular matrix and induces differentiation of fibroblasts to
      myofibroblasts, which further worsens fibrosis. Although TGF-beta has been
      extensively investigated in fibrosis, the roles of several components of its
      signaling pathway are still unknown. Endoglin is a coreceptor for TGF-beta and is
      known to modulate TGF-beta signaling. Therefore, endoglin could enhance the
      effects of TGF-beta in fibrosis or act as an inhibitor. Multiple studies have
      been conducted that support either hypothesis. Elucidating the exact role of
      endoglin in TGF-beta signaling during fibrosis is important in understanding the
      process of fibrosis and could lead to the development of better treatments.

PMID- 22608565
TI  - rhAPC reduces the endothelial cell permeability via a decrease of contractile
      tensions induced by endothelial cells.
AB  - All cells generate contractile tension. This strain is crucial for mechanically
      controlling the cell shape, function and survival. In this study, the CellDrum
      technology quantifying cell's (the cellular) mechanical tension on a pico-scale
      was used to investigate the effect of lipopolysaccharide (LPS) on human aortic
      endothelial cell (HAoEC) tension. The LPS effect during gram-negative sepsis on
      endothelial cells is cell contraction causing endothelium permeability increase.
      The aim was to finding out whether recombinant activated protein C (rhAPC) would
      reverse the endothelial cell response in an in-vitro sepsis model. In this study,
      the established in-vitro sepsis model was confirmed by interleukin 6 (IL-6)
      levels at the proteomic and genomic levels by ELISA, real time-PCR and reactive
      oxygen species (ROS) activation by florescence staining. The thrombin cellular
      contraction effect on endothelial cells was used as a positive control when the
      CellDrum technology was applied. Additionally, the Ras homolog gene family,
      member A (RhoA) mRNA expression level was checked by real time-PCR to support
      contractile tension results. According to contractile tension results, the
      mechanical predominance of actin stress fibers was a reason of the increased
      endothelial contractile tension leading to enhanced endothelium contractility and
      thus permeability enhancement. The originality of this data supports firstly the
      basic measurement principles of the CellDrum technology and secondly that rhAPC
      has a beneficial effect on sepsis influenced cellular tension. The technology
      presented here is promising for future high-throughput cellular tension analysis
      that will help identify pathological contractile tension responses of cells and
      prove further cell in-vitro models.

PMID- 22608566
TI  - Incidence and risk factors of AIDS-defining cancers in a cohort of HIV-positive
      adults: Importance of the definition of incident cases.
AB  - BACKGROUND: The aim of this study was to investigate the incidence and risk
      factors for the development of AIDS-defining cancers (ADCs); and to investigate
      the effect of making different assumptions on the definition of incident cases.
      METHODS: A multicentre cohort study was designed. Poisson regression was used to
      assess incidence and risk factors. To account for misclassification, incident
      cases were defined using lag-times of 0, 14 and 30 days after enrolment. RESULTS:
      A total of 6393 HIV-positive subjects were included in the study. The incidences
      of ADCs changed as the lag periods were varied from 0 to 30 days. Different risk
      factors emerged as the definition of incident cases was changed. For a lag time
      of 0, the risk of Kaposi sarcoma [KS] and non-Hodgkin lymphoma [NHL] increased at
      CD4 counts <200/ml. HAART was associated with lower risk of NHL and KS. Men who
      had sex with men had a higher risk of KS. KS and NHL were not associated with
      viral load, gender, or hepatitis B or C. The results were similar for a lag-time
      of 14 and 30 days; however, hepatitis C was significantly associated with NHL.
      CONCLUSIONS: This analysis shows the importance of the definition of incident
      cases in cohort studies. Alternative definitions gave different incidence
      estimates, and may have implications for the analysis of risk factors.

PMID- 22608567
TI  - Alcohol consumption patterns and sexual risk behavior among female sex workers in
      two South Indian communities.
AB  - BACKGROUND: HIV transmission in India is primarily heterosexual and there is a
      concentrated HIV epidemic among female sex workers (FSWs). Earlier reports
      demonstrate that many FSWs consume alcohol regularly before sexual encounters.
      This qualitative study is part of a larger quantitative study designed to assess
      alcohol consumption patterns among female sex workers and their association with
      sexual risk taking. Here we investigate the environmental influence, reasons for
      and consequences of consuming alcohol in the FSW population. METHODS: Trained
      staff from two Non-Governmental Organizations in Andhra Pradesh and Kerala
      conducted semi-structured interviews with 63 FSWs in Chirala, Andhra Pradesh (n =
      35) and Calicut, Kerala (n = 28) following extensive formative research,
      including social mapping and key informant interviews, to assess drinking
      patterns and sexual risk behaviors. RESULTS: FSWs reported consuming alcohol in
      multiple contexts: sexual, social, mental health and self-medication. Alcohol
      consumption during sexual encounters with clients was usually forced, but some
      women drank voluntarily. Social drinking took place in public locations such as
      bars and in private locations including deserted buildings, roads and inside
      autorickshaws (motorcycle taxis). Consequences of alcohol consumption included
      failure to use condoms and to collect payments from clients, violence, legal
      problems, gastrointestinal side effects, economic loss and interference with
      family responsibilities. CONCLUSION: FSWs consume alcohol in multilevel contexts.
      Alcohol consumption during transactional sex is often forced and can lead to
      failure to use condoms. Social drinkers consume alcohol with other trusted FSWs
      for entertainment and to help cope with psychosocial stressors. There are
      multiple reasons for and consequences of alcohol consumption in this population
      and future interventions should target each specific aspect of alcohol use.

PMID- 22608568
TI  - The socioeconomic impact of drug-related crimes in Chile.
AB  - BACKGROUND: Illegal drug use and trafficking are closely connected to crime. This
      article estimates the socioeconomic impact of this connection in Chile. METHODS:
      Goldstein's tripartite model was applied quantifying drug-crime connections and
      then using those estimates to measure the socioeconomic impact of drug-related
      crimes. This was estimated in terms of both the monetary cost of law enforcement,
      and lost productivity due to incarceration. This socioeconomic impact can be
      divided into: (a) the direct costs arising from infractions to Chile's Drug Law,
      and the indirect costs originated by crimes linked only partially to drug
      consumption and trafficking; (b) is measured in productivity losses, as well as
      in costs to the three branches of Chile's criminal justice system (police,
      judiciary, and prisons); and (c) is attributed to the three illicit drugs most
      prevalent in Chile: cannabis, cocaine hydrochloride (CH) and cocaine base paste
      (CBP). RESULTS: The socioeconomic impact of Chile's drug-crime relationship in
      2006 is estimated to be USD 268 million. Out of this amount, 36% is spent on
      national Drug Law enforcement, and the remaining 64% comes from the connection of
      drug use and trafficking with non-Drug-Law-related crimes. The police bear the
      largest share of drug enforcement costs (32%), followed by penitentiaries (25%).
      Productivity losses due to incarceration for drug-related crimes represent 29% of
      the total impact. 53% of the costs are attributable to CBP, 29% to CH, and the
      remaining 18% to cannabis. The impact of CBP is greater when indirect costs are
      taken into account, although direct costs are primarily associated with CH.
      CONCLUSION: The majority of costs is attributed to the trafficking and
      consumption of CBP, a drug with a relatively low prevalence. Based on the
      results, this study suggests reviewing drug enforcement policies to differentiate
      them according to the social and individual harm caused by each drug.

PMID- 22608569
TI  - Effect of bronchodilator treatment on the incidence of postoperative atrial
      fibrillation after cardiac surgery.
AB  - OBJECTIVE: We sought to examine the effects of bronchodilator treatment on the
      incidence of postoperative atrial fibrillation (POAF) after cardiac surgery.
      METHODS: A cross-sectional design using a retrospective chart review was
      performed in patients who underwent cardiac surgery. Those who had previous
      atrial fibrillation or preoperative bronchodilator treatment were excluded from
      the final sample (n = 506). The Statistical Package for the Social Sciences
      (SPSS, Inc., Chicago, IL) was used for statistical analyses. RESULTS: The
      incidence of POAF in this study was 27.9%, and was associated with age (P < .01)
      and type of cardiac surgery (P < .05), indicating that increasing age, and
      combined cardiac surgery were more likely to precipitate POAF. Bronchodilator
      treatment did not increase POAF. However, combined therapy significantly (P <
      .01) precipitated more POAF (48.7%) than did albuterol (21.4%) or levalbuterol
      (18.5%). CONCLUSIONS: Postoperative atrial fibrillation continues to be a common
      complication after cardiac surgery. Bronchodilator treatment with either
      albuterol or levalbuterol did not precipitate POAF, unless both agents were given
      to the same patients postoperatively.

PMID- 22608571
TI  - Aspergillus species recombinant antigens for serodiagnosis of farmer's lung
      disease.

PMID- 22608573
TI  - Adverse reactions to vaccines practice parameter 2012 update.

PMID- 22608574
TI  - Caring for the smoking asthmatic patient.

PMID- 22608572
TI  - Helminth infection is associated with decreased basophil responsiveness in human
      beings.

PMID- 22608575
TI  - Adult-onset systemic mastocytosis in monozygotic twins with KIT D816V and JAK2
      V617F mutations.

PMID- 22608576
TI  - Modulating electron transfer properties of gold nanoparticles for efficient
      biosensing.
AB  - Present study concerns modulating the electron transfer properties of gold
      nanoparticles through amino acid induced coupling among them. In addition to
      conductivity, the amino functionalization of the nanoparticles results in
      enhanced activity and operational stability of the biosensor fabricated using the
      same. Nanoparticles synthesized using amino acid as reducing agent (average
      diameter-20 nm), incorporate the natural coupling property of amino acids and are
      seen to align in a chain-like arrangement. The coupling of the individual
      nanoparticles to form chain like structure was confirmed by both absorption
      spectroscopy as well as transmission electron microscopy. The glucose biosensor
      developed by adsorption of glucose oxidase (GOx) enzyme onto these coupled gold
      nanoparticles showed enhanced efficiency as compared to the one with glucose
      oxidase immobilized onto gold nanoparticles synthesized using the conventional
      method (trisodium citrate as reducing agent). The fabricated biosensor
      demonstrated a wide linear concentration range from 1 MUM-5mM and a high
      sensitivity of 47.2 MUA mM(-1) cm(-2). Also, an enhanced selectivity to glucose
      was observed with negligible interference in the physiological range, from easily
      oxidizable biospecies, e.g. uric acid and ascorbic acid. Furthermore, the
      electrochemical biosensor has excellent long term stability- retaining greater
      than 85% of the biosensor activity up to 60 days.

PMID- 22608577
TI  - Tolerance and opioid-induced hyperalgesia. Is a divorce imminent?

PMID- 22608578
TI  - A standard measure of persistent bodily pain that is quick and easy to use, valid
      and stable over time.

PMID- 22608579
TI  - Intraoperative tidal volume: does it matter?

PMID- 22608570
TI  - Corticosteroid use and bone mineral accretion in children with asthma: effect
      modification by vitamin D.
AB  - BACKGROUND: The adverse effects of corticosteroids on bone mineral accretion
      (BMA) have been well documented. Vitamin D insufficiency, a prevalent condition
      in the pediatric population, has also been associated with decreased bone mineral
      density (BMD). OBJECTIVE: We sought to determine whether children with asthma who
      have lower vitamin D levels are more susceptible to the negative effects of
      corticosteroids on BMD over time. METHODS: Children aged 5 to 12 years with mild
      to-moderate asthma who participated in the Childhood Asthma Management Program
      were followed for a mean of 4.3 years. Total doses of inhaled corticosteroids and
      oral corticosteroids (OCSs) were recorded, serum 25-hydroxyvitamin D3 levels were
      measured at the beginning of the trial, and serial dual-energy x-ray
      absorptiometry scans of the lumbar spine were performed. Annual BMA rates were
      defined as follows: [(BMD at 4 years' follow-up - BMD at baseline)/4 years].
      RESULTS: BMA was calculated for 780 subjects. In boys baseline vitamin D levels
      significantly modified the relationship between OCSs and BMA (vitamin D * OCS
      interaction, P= .023). Stratification by vitamin D levels showed a decrease in
      BMA with increased use of OCSs in vitamin D-insufficient boys only (P< .001).
      Compared with vitamin D-sufficient boys, vitamin D-insufficient boys exposed to
      more than 2 courses of OCSs per year had twice the decrease in BMA rate (relative
      to boys who were OCS unexposed). CONCLUSIONS: Vitamin D levels significantly
      modified the effect of OCSs on BMA in boys. Further research is needed to examine
      whether vitamin D supplementation in children with poorly controlled asthma might
      confer benefits to bone health.

PMID- 22608580
TI  - Reliability of assessment of nasal flow rate for nostril selection during
      nasotracheal intubation.
AB  - STUDY OBJECTIVE: To evaluate the reliability of assessments of nasal flow rate
      for improved nostril selection for nasotracheal intubation. DESIGN: Prospective,
      randomized, double-blinded study. SETTING: Operating room of a university
      affiliated hospital. PATIENTS: 118 ASA physical status 1 and 2 patients, aged 18
      65 years, scheduled for elective maxillofacial and oral surgery requiring
      nasotracheal intubation. INTERVENTIONS: Patients were randomized to the left or
      right nostril groups. Forced vital capacity (FVC) and forced expiratory volume in
      one second (FEV(1)) through the mouth and each nostril were measured before
      anesthesia induction. MEASUREMENTS: The relationship between the rate of airflow
      through the selected nostril and frequency of epistaxis and navigability of the
      nasotracheal tube were evaluated. MAIN RESULTS: There were no significant
      differences in the frequency of epistaxis and degree of navigability of the
      tracheal tube between the left and right nostril groups. In both nostril groups,
      patients who suffered epistaxis showed significantly less FEV(1) and FEV(1)/FVC
      values than did patients without epistaxis (P < 0.05). In addition, in both
      groups patients who passed the tube easily showed significantly higher FEV(1) and
      FEV(1)/FVC values than did patients who passed the tube with resistance or failed
      tube passage (P < 0.05). CONCLUSION: Measurement of nasal flow rate is a useful
      clinical method for choosing a nostril for nasotracheal intubation.

PMID- 22608581
TI  - Comparison of noninvasive cardiac output measurements using the Nexfin monitoring
      device and the esophageal Doppler.
AB  - STUDY OBJECTIVE: To evaluate the validity of cardiac output (CO) measurements
      obtained using the Nexfin device in comparison to those obtained with the
      esophageal Doppler in steady-state conditions and after phenylephrine
      administration. DESIGN: Prospective observational study. SETTING: Operating room
      of a North American academic medical center. PATIENTS: 25 ASA physical status 1,
      2, and 3 patients referred for abdominal or orthopedic surgeries. INTERVENTIONS:
      After endotracheal intubation, patients who presented with a 20% or greater
      decrease in mean arterial pressure (MAP) received an intravenous (IV) bolus of
      100 MUg of phenylephrine. If MAP was still 20% lower than the patient's baseline
      level at least 10 minutes after the first vasopressor treatment, a second bolus
      of 100 MUg of phenylephrine was given. MEASUREMENTS: CO was measured
      simultaneously by esophageal Doppler (CO(ED)) and Nexfin (CO(NXF)) at baseline
      and when blood pressure peaked after an IV 100 MUg phenylephrine bolus.
      Comparisons were then made between the two devices to evaluate the ability of the
      Nexfin device to track changes in CO. MAIN RESULTS: 66 pairs of data were
      obtained. Mean CO(ED) and CO(NXF) were 4.7 +/- 1.8 L/min and 5.6 +/- 2.0 L/min,
      respectively. There was a significant relationship between CO(ED) and CO(NXF)
      (r(2) = 0.82; P < 0.001). The agreement between CO(ED) and CO(NXF) was 0.88 +/-
      0.86 L/min (Bland Altman). The mean percent error (Critchley and Critchley) of
      CO(NXF) versus CO(ED) was 37%. Trending analysis found a 94% concordance between
      changes in CO(ED) and CO(NXF) after phenylephrine administration. CONCLUSIONS:
      Intraoperative CO measurement using the Nexfin device has a strong correlation
      with CO measured by esophageal Doppler.

PMID- 22608582
TI  - Prevention of propofol-induced pain in children: pretreatment with small doses of
      ketamine.
AB  - STUDY OBJECTIVE: To evaluate the efficacy of ketamine in preventing propofol
      injection pain in children. DESIGN: Prospective, randomized, double-blinded,
      placebo-controlled study. SETTING: University-affiliated hospital. PATIENTS: 192
      ASA physical status 1 and 2 pediatric patients. INTERVENTIONS: Patients were
      randomly assigned to 4 groups. Group S (control) received normal saline as a
      placebo; Group K1, Group K3, and Group K5 received 0.1 mg/kg, 0.3 mg/kg, and 0.5
      mg/kg of ketamine, respectively. Fifteen seconds after the ketamine injection,
      patients were injected with propofol at a rate of 12 mL/min until loss-of-eyelash
      reflex. MEASUREMENT: Pain was evaluated blindly at the time of induction using a
      4-point scale: 0 = no pain, 1 = mild pain, 2 = moderate pain, and 3 = severe
      pain. Adverse effects were recorded. Characteristics of induction of anesthesia,
      such as dose of propofol and time from propofol injection to loss of
      consciousness (induction duration), were noted. MAIN RESULTS: 39 (84.8%) Group S
      (control) patients had pain. Pretreatment with ketamine reduced the frequency of
      pain significantly to 56.5%, 17.0%, and 14.9% in Groups K1, K3, and K5,
      respectively. Furthermore, the frequency of moderate and severe pain in Group K1
      (21.8%), Group K3 (6.4%), and Group K5 (4.3%) was significantly (P < 0.001,
      respectively) reduced compared with Group S (76.1%). Moreover, the dose of
      propofol for induction in Group K5 was smaller than in Group S, Group K1, and
      Group K3 (P < 0.05). One patient in Group K5 had emergence agitation. CONCLUSION:
      Pretreatment with a small dose of ketamine (0.3 mg/kg) reduced the frequency and
      intensity of propofol injection pain without severe adverse effects.

PMID- 22608583
TI  - Use of sugammadex in patients with a history of pulmonary disease.
AB  - STUDY OBJECTIVE: To evaluate the safety and efficacy of sugammadex for reversal
      of rocuronium-induced neuromuscular blockade in patients with pulmonary disease.
      DESIGN: Phase III, randomized, multicenter, parallel-group, comparative, safety
      assessor blinded study. SETTING: Nine hospital sites. PATIENTS: 77 ASA physical
      status 2 and 3 patients, aged >= 18 years, with a history of pulmonary disease,
      and scheduled for surgery with general anesthesia requiring neuromuscular
      blockade. INTERVENTIONS: Following anesthesia induction, patients received
      rocuronium 0.6 mg/kg with 0.15 mg/kg maintenance doses as needed. Patients were
      randomized to receive sugammadex 2 mg/kg or 4 mg/kg after the last rocuronium
      dose at reappearance of the second twitch. MEASUREMENTS: Safety evaluations
      included adverse events, laboratory parameters, vital signs, and evidence of
      recurrent or residual neuromuscular blockade. Efficacy was evaluated as the time
      from sugammadex administration to recovery of the train-of-four (TOF) ratio to >=
      0.9. MAIN RESULTS: Safety was comparable between doses, with no evidence of
      residual or recurrent neuromuscular blockade. Two bronchospasm cases were
      reported (4 mg/kg group), both in patients with asthma who received desflurane
      for anesthesia maintenance. Geometric mean (95% confidence interval) times to a
      TOF ratio of >= 0.9 were 2.1 (1.7 - 3.1) min (2 mg/kg) and 1.8 (1.5 - 2.7) min (4
      mg/kg). CONCLUSION: Sugammadex 2 mg/kg and 4 mg/kg were well tolerated and
      effective in patients with a history of pulmonary disease. Bronchospasm is a
      possibility when administering sugammadex to patients with underlying pulmonary
      disease.

PMID- 22608584
TI  - Bilateral multi-injection iliohypogastric-ilioinguinal nerve block in conjunction
      with neuraxial morphine is superior to neuraxial morphine alone for postcesarean
      analgesia.
AB  - STUDY OBJECTIVE: To determine whether bilateral iliohypogastric and ilioinguinal
      (IHII) peripheral nerve blocks, given in conjunction with neuraxial morphine,
      reduce postcesarean analgesic requirements and side effects, resulting in
      improved maternal satisfaction. DESIGN: Randomized, prospective, double-blinded,
      placebo-controlled study. SETTING: Labor and delivery suite at Johns Hopkins
      Hospital. PATIENTS: 34 women scheduled for elective cesarean delivery.
      INTERVENTIONS: Patients were randomized to receive IHII nerve blocks bilaterally,
      with either total 24 mL of 0.5% bupivacaine or normal saline, following cesarean
      delivery via Pfannensteil incision with a standard intrathecal dose of 12 mg of
      0.75% bupivacaine with 10 ug of fentanyl and 200 ug of preservative-free
      morphine. MEASUREMENTS: Patients were assessed at 0, 6, 12, 18, and 24 hours
      postoperatively. Visual analog scale (VAS) pain scores at rest were recorded at
      each time period. Analgesic use, patients' perception of nausea, vomiting,
      pruritus, and their overall satisfaction with their analgesia were recorded for
      the first 24 hours. MAIN RESULTS: Lower VAS pain scores were seen in the
      bupivacaine group at 6, 12, 18, and 24 hours postoperatively (P = 0.01, P < 0.01,
      0.02, and 0.04, respectively). A longer mean time to first rescue dose of
      ketorolac was noted in the bupivacaine group (14.3 +/- 1.8 hrs) than the saline
      group (mean 5.6 +/-1.1 hrs), (P < 0.01). Fewer patients in the bupivacaine group
      made requests for acetaminophen 500 mg/oxycodone 5 mg in the first 24 hours.
      Satisfaction was greater in the bupivacaine group. No difference in side effects
      was noted between groups. CONCLUSIONS: Bilateral multilevel injection IHII nerve
      blocks result in lower resting VAS pain scores, lower analgesic requirements, and
      greater satisfaction following cesarean delivery in patients who received
      neuraxial morphine.

PMID- 22608585
TI  - Comparison of noninvasive continuous arterial waveform analysis (Nexfin) with
      transthoracic Doppler echocardiography for monitoring of cardiac output.
AB  - STUDY OBJECTIVES: To compare the Nexfin cardiac output (CO) with the CO obtained
      from transthoracic Doppler echocardiography (TTE) during routine cardiac function
      screening. DESIGN: Observational clinical study. SETTING: Echocardiography
      laboratory. PATIENTS: 40 ASA physical status 1 and 2 patients scheduled for
      routine TTE examination. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In
      40 patients scheduled for routine TTE examination, we obtained simultaneous CO
      measurements with Doppler ultrasound and derived from Nexfin blood pressure
      measurements. Correlation and level of agreement between Nexfin and TTE were
      analyzed using Pearson correlation coefficient and Bland-Altman plots. The
      Pearson correlation coefficient for Nexfin versus TTE was 0.68 (CI: 0.46 - 0.82,
      P < 0.0001). Bland-Altman analysis showed a bias of 0.51 +/- 1.1 L/min and limits
      of agreement of -1.6 to 2.6 L/min, with a percentage error of 39%. CONCLUSIONS:
      Considering limits of precision of CO measurements with Doppler echocardiography
      (+/- 30%), the agreement between noninvasive CO measurement with the Nexfin and
      TTE is reasonable.

PMID- 22608586
TI  - A profound case of neurally mediated syncope with asystole after septoplasty.
AB  - Vasovagal syncope (VVS) is an alarming yet benign condition that may present
      postoperatively for the first time in otherwise healthy patients. Although VVS is
      associated anecdotally with nasal manipulation, no data have been found to
      quantify this incidence with otolaryngology surgeries. We present a case of
      profound, recurrent syncope and documented asystole with an initial diagnosis of
      glossopharyngeal neuralgia. We conclude with a discussion of neurally mediated
      syncope particular to the perioperative setting. It is essential to recognize
      neurocardiogenic etiology to differentiate it from other more concerning causes
      of syncope and asystole.

PMID- 22608587
TI  - Perioperative retinoic acid syndrome in a patient with acute promyelocytic
      leukemia.
AB  - All-trans retinoic acid (ATRA), a vitamin A derivative, is prescribed for
      induction of chemotherapy in patients with acute promyelocytic leukemia. Like
      other chemotherapy agents, ATRA has an adverse effect known as retinoic acid
      syndrome. The case of a 22 year old woman with acute promyelocytic leukemia, who
      received ATRA and subsequently developed retinoic acid syndrome, is presented.
      The patient's symptoms resolved after administration of dexamethasone, allowing
      the completion of chemotherapy without further complications.

PMID- 22608588
TI  - Treatment of refractory intracranial hypertension with 23.4% saline in children
      with severe traumatic brain injury.
AB  - The safety and efficacy of osmotic therapy with mannitol and 3% saline in the
      pediatric head-injured population has been widely reported; the use of 23.4%
      saline in children for the treatment of refractory intracranial hypertension has
      not. The clinical and physiologic responses of multiple 23.4% saline boluses in
      two children with severe traumatic brain injury (TBI) are presented. No
      complications were associated with the use of 23.4% saline in either patient.

PMID- 22608589
TI  - The response to methylene blue in patients with severe hypotension during liver
      transplantation.
AB  - Methylene blue is a useful therapy for catecholamine-resistant vasoplegic shock.
      Three cases of methylene blue administration for the treatment of catecholamine
      resistant hypotension during orthotopic liver transplantation are presented.

PMID- 22608590
TI  - Perioperative atrial fibrillation and epidural anesthesia: case report and review
      of the literature.
AB  - A case of new-onset atrial fibrillation subsequent to activation of neuraxial
      anesthesia is presented. The development of atrial fibrillation was temporally
      related to placement and dosing of an epidural catheter, and may have been
      triggered by a vagal response to dosing of the anesthetic or the resulting
      treatment with fluid and an adrenergic agent. The literature on the acute
      preoperative management of atrial fibrillation and the implications of atrial
      fibrillation for the patient undergoing regional anesthesia are reviewed.

PMID- 22608591
TI  - Perspectives on transdermal scopolamine for the treatment of postoperative nausea
      and vomiting.
AB  - Transdermal scopolamine, a patch system that delivers 1.5 mg of scopolamine
      gradually over 72 hours following an initial bolus, was approved in the United
      States in 2001 for the prevention of postoperative nausea and vomiting (PONV) in
      adults. Scopolamine (hyoscine) is a selective competitive anatagonist of
      muscarinic cholinergic receptors. Low serum concentrations of scopolamine produce
      an antiemetic effect. Transdermal scopolamine is effective in preventing PONV
      versus placebo [relative risk (RR)=0.77, 95% confidence interval (CI), 0.61-0.98,
      P = 0.03] and a significantly reduced risk for postoperative nausea (RR=0.59, 95%
      CI, 0.48-0.73, P < 0.001), postoperative vomiting (RR=0.68, 95% CI, 0.61-0.76, P
      < 0.001), and PONV (RR 0.73, 95% CI, 0.60-0.88, P = 001) in the first 24 hours
      after the start of anesthesia.

PMID- 22608592
TI  - Out-of-operating room anesthesia: use of the AnaConDa vaporizer with anesthesia.

PMID- 22608593
TI  - Pseudohyperkalemia in the setting of chronic lymphocytic leukemia.

PMID- 22608594
TI  - A novel, simple method of delivering oxygen for endoscopic procedures.

PMID- 22608595
TI  - Perioperative management of a pediatric patient with short-chain acyl-CoA
      dehydrogenase deficiency.

PMID- 22608596
TI  - Noninvasive removal of an entrapped supraclavicular catheter.

PMID- 22608597
TI  - Falsely low pulse oximetry values caused by aortocaval fistula.

PMID- 22608598
TI  - Failure of the Easy Cap II CO2 detector to indicate esophageal intubation.

PMID- 22608599
TI  - [Crohn's disease with positive serological markers for coeliac disease].

PMID- 22608600
TI  - Biomechanical cadaver testing of a fixed-angle plate in comparison to tension
      wiring and screw fixation in transverse patella fractures.
AB  - INTRODUCTION: Operative treatment of patella fractures is frequently associated
      with implant failure and secondary dislocation which can be attributed to the
      employed hardware. Therefore, a 2.7 mm fixed-angle plate designed for the
      treatment of patella fractures was tested biomechanically against the currently
      preferred methods of fixation. It was hypothesized that under simulated cyclic
      loading fixed-angle plating would be superior to modified anterior tension wiring
      or cannulated lag screws with anterior tension wiring. MATERIALS AND METHODS:
      Eighteen human cadaver knees, matched by bone mineral density and age, were
      divided into three groups of six. After setting a transverse patella fracture
      each group received one of the osteosyntheses mentioned above. Repetitive testing
      over 100 cycles was performed at non-destructive loads by simulating knee motion
      from 90 degrees  flexion to full extension. RESULTS: Anterior tension wiring as
      well as lag screws with tension wiring showed significant fracture displacement
      after the initial cycle already. Both constructs, lag screws plus wiring (3.7 +/-
      2.7 mm) as well as tension wiring alone (7.1 +/- 2.2 mm) displayed fracture
      displacement of >2 mm which is clinically regarded as failure. Those patellae
      stabilized with fixed-angle plates showed no significant fracture gap widening
      after completion of 100 cycles (0.7 +/- 0.5 mm). The differences between the
      fixed-angle plate group and the other two groups were statistically significant
      (p<0.05). CONCLUSION: In contrast to modified anterior tension wiring and
      cannulated lag screws with anterior tension wiring the bilateral fixed-angle
      plate was the only fixation device to stabilize transverse patella fractures
      securely and sustainably.

PMID- 22608601
TI  - Focused ultrasound for traumatic ankle pain in the emergency department.

PMID- 22608602
TI  - A case of acute long-head biceps tendon rupture.

PMID- 22608603
TI  - Spontaneous retroperitoneal hemorrhage in a dialysis patient.
AB  - BACKGROUND: Patients with end-stage renal disease (ESRD) often present to the
      Emergency Department with a multitude of complaints. Abnormal vital signs and a
      chief complaint of pain can produce a diagnosis ranging from a cardiac etiology
      to an infectious source. OBJECTIVES: Our goal is to discuss a case in which an
      ESRD dialysis patient presented with a rare, life-threatening emergency. CASE
      REPORT: A 55-year-old man with ESRD presented with acute abdominal pain and
      hypotension caused by a spontaneous retroperitoneal hemorrhage. CONCLUSION: This
      case report demonstrates the necessity of having broad differential diagnoses
      when evaluating patients with ESRD.

PMID- 22608604
TI  - Introduction to the special issue on "Advances in Biomedical Engineering and
      Computing: the MEDICON Conference Case" selected papers from MEDICON 2010.

PMID- 22608605
TI  - Changes associated with lenalidomide treatment in the gene expression profiles of
      patients with del(5q).
AB  - We used microarray profiling to investigate the direct effects of lenalidomide on
      gene expression in isolated CD14(+) monocytes from 6 patients with del(5q). Our
      data demonstrate that changes in genes involved the tumor necrosis factor (TNF)
      signaling pathway and the bone marrow stroma, suggesting that treatment with
      lenalidomide may help restore the damaged niche and suppress the TNF signaling
      pathway. BACKGROUND: Lenalidomide is an effective treatment for patients with
      del(5q) and myelodysplastic syndrome (MDS) The exact mechanism of lenalidomide
      function and its impact on the prognosis of patients is not known exactly.
      MATERIALS AND METHODS: We used gene expression profiling to study the effect of
      lenalidomide therapy in peripheral blood CD14(+) monocytes of 6 patients with
      del(5q) and MDS. RESULTS: After lenalidomide treatment, genes involved in the
      tumor necrosis factor (TNF) signaling pathway that were upregulated in the
      patients before treatment decreased to the healthy control baseline expression
      level. This change in gene expression, in conjunction with increased expression
      of repressed genes that affect the stem cell niche (ie, CXCR4 and CRTAP), may
      exert a positive effect on treated patients. In contrast, we found that increased
      expression of the ARPC1B gene may have a negative impact on the stability of
      patient remission. CONCLUSION: The observed changes in gene expression described
      here may contribute to the identification of pathways that are affected by
      lenalidomide, which may help to explain the effects of this drug.

PMID- 22608606
TI  - Precipitation of arsenic sulphide from acidic water in a fixed-film bioreactor.
AB  - Arsenic (As) is a toxic element frequently present in acid mine waters and
      effluents. Precipitation of trivalent arsenic sulphide in sulphate-reducing
      conditions at low pH has been studied with the aim of removing this hazardous
      element in a waste product with high As content. To achieve this, a 400m L fixed
      film column bioreactor was fed continuously with a synthetic solution containing
      100mg L(-1) As(V), glycerol and/or hydrogen, at pH values between 2.7 and 5. The
      highest global As removal rate obtained during these experiments was close to
      2.5mg L(-1)h(-1). A switch from glycerol to hydrogen when the biofilm was mature
      induced an abrupt increase in the sulphate-reducing activity, resulting in a
      dramatic mobilisation of arsenic due to the formation of soluble thioarsenic
      complexes. A new analytical method, based on ionic chromatography, was used to
      evaluate the proportion of As present as thioarsenic complexes in the bioreactor.
      Profiles of pH, total As and sulphate concentrations suggest that As removal
      efficiency was linked to solubility of orpiment (As(2)S(3)) depending on pH
      conditions. Molecular fingerprints revealed fairly homogeneous bacterial
      colonisation throughout the reactor. The bacterial community was diverse and
      included fermenting bacteria and Desulfosporosinus-like sulphate-reducing
      bacteria. arrA genes, involved in dissimilatory reduction of As(V), were found
      and the retrieved sequences suggested that As(V) was reduced by a
      Desulfosporosinus-like organism. This study was the first to show that As can be
      removed by bioprecipitation of orpiment from acidic solution containing up to
      100mg L(-1) As(V) in a bioreactor.

PMID- 22608607
TI  - Comparison of drinking water treatment process streams for optimal
      bacteriological water quality.
AB  - Four pilot-scale treatment process streams (Stream 1 - Conventional treatment
      (coagulation/flocculation/dual media filtration); Stream 2 - Magnetic ion
      exchange (MIEX)/Conventional treatment; Stream 3 - MIEX/Conventional
      treatment/granular activated carbon (GAC) filtration; Stream 4 -
      Microfiltration/nanofiltration) were commissioned to compare their effectiveness
      in producing high quality potable water prior to disinfection. Despite receiving
      highly variable source water quality throughout the investigation, each stream
      consistently reduced colour and turbidity to below Australian Drinking Water
      Guideline levels, with the exception of Stream 1 which was difficult to manage
      due to the reactive nature of coagulation control. Of particular interest was the
      bacteriological quality of the treated waters where flow cytometry was shown to
      be the superior monitoring tool in comparison to the traditional heterotrophic
      plate count method. Based on removal of total and active bacteria, the treatment
      process streams were ranked in the order: Stream 4 (average log removal of 2.7) >
      Stream 2 (average log removal of 2.3) > Stream 3 (average log removal of 1.5) >
      Stream 1 (average log removal of 1.0). The lower removals in Stream 3 were
      attributed to bacteria detaching from the GAC filter. Bacterial community
      analysis revealed that the treatments affected the bacteria present, with the
      communities in streams incorporating conventional treatment clustering with each
      other, while the community composition of Stream 4 was very different to those of
      Streams 1, 2 and 3. MIEX treatment was shown to enhance removal of bacteria due
      to more efficient flocculation which was validated through the novel application
      of the photometric dispersion analyser.

PMID- 22608608
TI  - Kinetics of UV inactivation of wastewater bioflocs.
AB  - Ultraviolet disinfection is a physical method of disinfecting secondary treated
      wastewaters. Bioflocs formed during secondary treatment harbor and protect
      microbes from exposure to ultraviolet (UV) light, and significantly decrease the
      efficiency of disinfection at high UV doses causing the tailing phenomena.
      However, the exact mechanism of tailing and the role of biofloc properties and
      treatment conditions are not widely understood. It is hypothesized that sludge
      bioflocs are composed of an easily disinfectable loose outer shell, and a
      physically stronger compact core inside that accounts for the tailing phenomena.
      Hydrodynamic shear stress was applied to the bioflocs to peel off the looser
      outer shell to isolate the cores. Biofloc and core samples were fractionated into
      narrow size distributions by sieving and their UV disinfection kinetics were
      determined and compared. The results showed that for bioflocs, the tailing level
      elevates as the biofloc size increases, showing greater resistance to
      disinfection. However, for the cores larger than 45MUm, it was found that the UV
      inactivation curves overlap, and show very close to identical inactivation
      kinetics. Comparing bioflocs and cores of similar size fraction, it was found
      that in all cases cores were harder to disinfect with UV light, and showed a
      higher tailing level. This study suggests that physical structure of bioflocs
      plays a significant role in the UV inactivation kinetics.

PMID- 22608609
TI  - Thiol-functionalised mesoporous silica-coated magnetite nanoparticles for high
      efficiency removal and recovery of Hg from water.
AB  - The preparation and testing of thiol-functionalised silica-coated magnetite
      nanoparticles (TF-SCMNPs) is described. The characteristics of these particles
      are assessed at different stages in the production process using X-ray
      diffraction (XRD), transmission electron microscopy (TEM), Fourier Transform
      Infrared Spectroscopy (FTIR), and a magnetometer. The particles were found to be
      almost spherical with a uniform mesoporous structure with a pore size of ~2.1nm.
      The particles were strongly responsive to an external magnetic field making
      separation from solution possible in less than 1min. The adsorption
      characteristics of the particles were quantified in a series of isotherm
      experiments using Hg(II) solution concentrations between 40 and 1000MUg l(-1) at
      adsorbent concentrations of 4 and 8mg l(-1). The adsorption capacity was higher
      than for other commonly used adsorbents with 90% of Hg(II) removed during the
      first 5min and equilibrium in less than 15min. Both the Langmuir and Freundlich
      isotherm models were applied to the isotherm data and the maximum adsorption
      capacity was achieved when the ratio of adsorbent to adsorbate was low. Both
      temperature and pH had an effect on adsorption but when the TF-SCMNPs were used
      for removal of Hg(II) from tap water and bottled water, which contained other
      ions, there appeared to be no interference. Hg(II) could be successfully desorbed
      using thiourea in a 3M HCl solution; this did not result in the destruction of
      the nanoparticles and they could subsequently be reused without loss of their
      activity in repetitive adsorption tests.

PMID- 22608610
TI  - Degradation pathway of the naphthalene azo dye intermediate 1-diazo-2- naphthol-4
      sulfonic acid using Fenton's reagent.
AB  - Degradation of naphthalene dye intermediate 1-diazo-2- naphthol-4-sulfonic acid
      (1,2,4-Acid) by Fenton process has been studied in depth for the purpose of
      learning more about the reactions involved in the oxidation of 1,2,4-Acid. During
      1,2,4-Acid oxidation, the solution color initially takes on a dark red, then to
      dark black associated with the formation of quinodial-type structures, and then
      goes to dark brown and gradually disappears, indicating a fast degradation of azo
      group. The observed color changes of the solution are a result of main reaction
      intermediates, which can be an indicator of the level of oxidization reached.
      Nevertheless, complete TOC removal is not accomplished, in accordance with the
      presence of resistant carboxylic acids at the end of the reaction. The
      intermediates generated along the reaction time have been identified and
      quantified. UPLC-(ESI)-TOF-HRMS analysis allows the detection of 19 aromatic
      compounds of different size and complexity. Some of them share the same accurate
      mass but appear at different retention time, evidencing their different molecular
      structures. Heteroatom oxidation products like SO(4)(2-) have also been
      quantified and explanations of their release are proposed. Short-chain carboxylic
      acids are detected at long reaction time, as a previous step to complete the
      process of dye mineralization. Finally, considering all the findings of the
      present study and previous related works, the evolution from the original 1,2,4
      Acid to the final products is proposed in a general reaction scheme.

PMID- 22608611
TI  - Musk fragrances, DEHP and heavy metals in a 20 years old sludge treatment reed
      bed system.
AB  - The Sludge Treatment Reed Bed (STRB) technology is a cost-efficient and
      environmentally friendly technology to dewater and mineralize surplus sludge from
      conventional wastewater treatment systems. Primary and secondary liquid sludge is
      loaded onto the surface of the bed over several years, where it is dewatered,
      mineralized and turned into a biosolid with a high dry matter content for use as
      an organic fertilizer on agricultural land. We analysed the concentrations of
      five organic micropollutants (galaxolide, tonalide, cashmeran, celestolide and
      DEHP) and six heavy metals (Pb, Ni, Cu, Cd, Zn and Cr) in the accumulated sludge
      in a 20-year old STRB in Denmark in order to assess the degradation and fate of
      these contaminants in a STRB and the relation to sludge composition. The results
      showed that the deposited sludge was dewatered to reach a dry matter content of
      29%, and that up to a third of the organic content of the sludge was mineralized.
      The concentrations of heavy metals generally increased with depth in the vertical
      sludge profile due to the dewatering and mineralization of organic matter, but in
      all cases the concentrations were below the European Union legal limits for
      agricultural land disposal. The concentrations of fragrances and DEHP ranged from
      10 to 9000 ng g(-1) dry mass. The attenuation of hydrophobic micropollutants from
      the top to the bottom layer of the reed bed ranged from 40 to 98%, except for
      tonalide which increased significantly with sludge depth, and consequently showed
      an unusual depth distribution of the galaxolide/tonalide ratio. This unexpected
      pattern may reflect changes imposed by a long storage time and/or different
      composition of the fresh sludge in the past. The lack of a significant decreasing
      DEHP concentration with sludge age might indicate that this compound is very
      persistent in STRBs. In conclusion the STRB was a feasible technology for sludge
      treatment before its land disposal.

PMID- 22608612
TI  - Psychiatry and neuroscience - history.

PMID- 22608613
TI  - Receptor signaling and the cell biology of synaptic transmission.
AB  - This volume describes a series of psychiatric and neuropsychiatric disorders,
      connects some aspects of somatic and psychiatric medicine, and describes various
      current and emerging therapies. The purpose of this chapter is to set the stage
      for the volume by developing the theoretical basis of synaptic transmission and
      introducing the various neurotransmitters and their receptors involved in the
      process. The intent is to provide not only a historical context through which to
      understand neurotransmitters, but a current contextual basis for understanding
      neuronal signal transduction and applying this knowledge to facilitate treatment
      of maladies of the brain and mind.

PMID- 22608614
TI  - Human genetics of schizophrenia.

PMID- 22608615
TI  - Neurological and psychiatric aspects of emotion.
AB  - Neurological and psychiatric aspects of emotions have been the focus of intense
      research for the past 30 years. Studies in both acute (e.g., stroke, traumatic
      brain injury (TBI)) and chronic (e.g., dementia, Parkinson's disease)
      neurological disorders demonstrated a high frequency of both depression and
      apathy. Studies in stroke and TBI reported a significant association between
      lesion location and depression. Both depression and apathy are significant
      predictors of poor recovery among patients with brain injuries, and of steeper
      cognitive and functional decline among patients with neurodegenerative disorders.
      Poor insight and judgment are frequently found among patients with brain injury
      or degeneration. There is increasing evidence that damage to specific brain
      regions, such as the ventromedial prefrontal cortex, is associated with
      inappropriate emotional reactions in social contexts and diminished anxiety and
      concern for the future. In severe cases, behavioural changes may also include
      poor decision-making in the social realm, deficits in goal-directed behavior, and
      lack of insight into these changes. Future studies will validate specific
      diagnostic criteria for the various cognitive, emotional, and behavioral problems
      reported among patients with neurological disorders, which may result in more
      specific and effective treatments.

PMID- 22608616
TI  - Research methods: cognitive neuropsychological methods.

PMID- 22608617
TI  - Structural imaging in psychiatric disorders.

PMID- 22608618
TI  - Human functional neuroimaging.

PMID- 22608619
TI  - Neurotransmitters and neuropeptides in depression.

PMID- 22608620
TI  - Animal models of psychiatric disorders.

PMID- 22608621
TI  - Psychiatric epidemiology.

PMID- 22608622
TI  - Emerging methods in the molecular biology of neuropsychiatric disorders.

PMID- 22608623
TI  - Clinical psychoneuroimmunology.

PMID- 22608624
TI  - Psychiatric rating scales.

PMID- 22608625
TI  - Unipolar depression.

PMID- 22608626
TI  - Bipolar disorder.
AB  - Bipolar disorder is a serious disorder of mood that is associated with
      considerable psychosocial and economic morbidity. Even though it is more common
      than previously thought, it has until relatively recently been somewhat neglected
      in terms of research when compared to disorders such as schizophrenia and major
      depression. Recent advances in the fields of nosology, epidemiology, and
      molecular genetics in particular have begun to unravel some of the complexity of
      this disorder and the next few years are likely to witness substantial changes to
      the ways in which the broad spectrum of bipolar disorders is diagnosed and
      managed.

PMID- 22608627
TI  - The neurobiology and treatment of late-life depression.

PMID- 22608628
TI  - Seasonal affective disorder.

PMID- 22608629
TI  - Biological and clinical framework for posttraumatic stress disorder.

PMID- 22608630
TI  - Generalized anxiety disorder.

PMID- 22608631
TI  - Panic disorder.

PMID- 22608632
TI  - Obsessive-compulsive disorder.

PMID- 22608633
TI  - Attention-deficit/hyperactivity disorder.

PMID- 22608635
TI  - Substance abuse disorders.

PMID- 22608634
TI  - Autism and related disorders.
AB  - The pervasive developmental disorders are a group of neurodevelopmental disorders
      that include autistic disorder, Asperger's disorder, pervasive developmental
      disorder - not otherwise specified (PDD-NOS), childhood disintegrative disorder
      (CDD), and Rett's disorder. All feature childhood onset with a constellation of
      symptoms spanning social interaction and communication and including atypical
      behavior patterns. The first three disorders (autistic disorder, Asperger's
      disorder, and PDD-NOS) are currently referred to as autism spectrum disorders,
      reflecting divergent phenotypic and etiological characteristics compared to
      Rett's disorder and CDD. This chapter reviews research and clinical information
      to appropriate medical diagnosis and treatment.

PMID- 22608636
TI  - Cognitive impairment in schizophrenia: profile, course, and neurobiological
      determinants.

PMID- 22608637
TI  - Eating disorders: anorexia and bulimia nervosa.

PMID- 22608638
TI  - Personality disorders.

PMID- 22608639
TI  - Psychiatric, nonmotor aspects of Parkinson's disease.

PMID- 22608640
TI  - Stroke.

PMID- 22608641
TI  - Huntington's disease.

PMID- 22608642
TI  - Sleep disorders.

PMID- 22608644
TI  - Psychiatric disorders among cancer patients.

PMID- 22608643
TI  - Depression and cardiovascular disorders.

PMID- 22608645
TI  - Chronic fatigue syndrome.

PMID- 22608646
TI  - Neurocognitive deficits in patients with human immunodeficiency virus infection.

PMID- 22608647
TI  - Gastrointestinal disorders.

PMID- 22608648
TI  - Role of psychotherapy in the management of psychiatric diseases.
AB  - Psychotherapy plays an essential role in the treatment of mental disorders. The
      use and research of psychological treatment strategies increased drastically over
      the past decade. The general efficacy of psychotherapy for the treatment of
      psychiatric diseases is proved and documented in several meta-analyses.
      Psychotherapy re-searchers have found solutions for acceptable study designs
      which account for the special character of these interventions and studied the
      efficacy of psychotherapeutic treatment in more than 1000 intervention
      trials.Meanwhile evidence-based psychotherapy approaches tailored to a specific
      diagnosis are dominating the field and question the basis of psychotherapy
      schools.A new field of research in psychotherapy is the neurobiological basis of
      mental disorders and the demonstration of neurobiological changes with psycho
      therapeutic treatment.

PMID- 22608649
TI  - Pharmacology and neuroimaging of antidepressant action.

PMID- 22608650
TI  - Antipsychotic drugs.

PMID- 22608651
TI  - Anxiolytics.

PMID- 22608652
TI  - Brain stimulation therapies for neuropsychiatric disease.
AB  - ECT is a well-established, effective, and safe treatment for many
      neuropsychiatric conditions, especially major depression. However, ECT is also
      associated with a high relapse rate, notable side-effects, and significant social
      stigma. Additionally, ECT is ineffective in a sizable minority of patients. Based
      on this, several other brain stimulation therapies are currently under active
      investigation. VNS is approved in many countries for the treatment of treatment
      resistant epilepsy and TRD. The available data suggest long-term VNS may have
      clinically significant antidepressant effects, though more data are needed to
      clarify how VNS might optimally be used in the treatment of neuropsychiatric
      disease.TMS offers a noninvasive technique for modulating neural function, and
      preliminary studies support acute efficacy in the treatment of depression and
      several other neuropsychiatric illnesses; results from more definitive studies
      are pending. Although early in development,MST may develop as a form of
      convulsive therapy that minimizes characteristic side-effects of ECT while
      achieving similar efficacy; clearly, more data from larger, controlled trials are
      needed, tDCS is in the early stages of development, but may prove to be an
      effective, noninvasive alternative for treatment-resistant patients with
      psychiatric disorders. DBS is the most invasive of these brain stimulation
      therapies, but may become an effective intervention for patients who have failed
      other available treatments (including ECT). Very preliminary data support the
      efficacy of DBS for specific neuropsychiatric conditions, and more definitive
      data are eagerly awaited. Beyond their potential efficacy for neuropsychiatric
      conditions, these various brain stimulation therapies may help improve our
      understand-ing of the neurobiology of neuropsychiatric disease.

PMID- 22608653
TI  - Chronotherapeutics (light and wake therapy) as a class of interventions for
      affective disorders.

PMID- 22608654
TI  - Pharmacogenetics of antidepressants and mood stabilizers.

PMID- 22608657
TI  - Plant-derived antimicrobials reduce Listeria monocytogenes virulence factors in
      vitro, and down-regulate expression of virulence genes.
AB  - Listeria monocytogenes (LM) is a major foodborne pathogen causing septicemia,
      meningitis and death in humans. LM infection is preceded by its attachment to and
      invasion of human intestinal epithelium followed by systemic spread. The major
      virulence factors in LM include motility, hemolysin and lecithinase production.
      Reducing LM attachment to and invasion of host tissue and production of virulence
      factors could potentially control listeriosis in humans. This study investigated
      the efficacy of sub-inhibitory concentrations (SICs, concentrations not
      inhibiting bacterial growth) of three, generally regarded as safe (GRAS)-status,
      plant-derived antimicrobial compounds in reducing LM attachment to and invasion
      of human colon adenocarcinoma (Caco-2) and human brain microvascular endothelial
      cells (HBMEC). Additionally, the effect of these compounds on the aforementioned
      LM virulence factors was studied. The compounds and their respective SICs used
      relative to their MICs were trans-cinnamaldehyde (TC 0.50mM, 0.75mM with the MIC
      of 0.90mM), carvacrol (CR 0.50mM, 0.65mM with the MIC of 0.75mM), and thymol (TY
      0.33mM, 0.50mM with the MIC of 0.60mM). All three-plant antimicrobials reduced LM
      adhesion to and invasion of Caco-2 and HBMEC (p<0.05). The compounds also
      decreased LM motility, hemolysin production and lecithinase activity (p<0.05).
      Real-time PCR data revealed that TC, CR, and TY down-regulated the expression of
      LM virulence genes by >3.0 folds compared to controls (p<0.05). Results suggest
      that TC, CR, and TY could potentially be used to control LM infection; however,
      in vivo studies are necessary to validate these results.

PMID- 22608658
TI  - A Bifidobacterium-based synbiotic product to reduce the transmission of C. jejuni
      along the poultry food chain.
AB  - With the ban of dietary antimicrobial agents, the use of probiotics, prebiotics
      and synbiotics has attracted a great deal of attention in order to improve
      intestinal health and control food-borne pathogens, which is an important concern
      for the production of safe meat and meat products. Recently, Campylobacter jejuni
      has emerged as a leading bacterial cause of food-borne gastroenteritis in humans,
      and epidemiological evidences indicate poultry and poultry products as the main
      source of human infection. This work aimed at the development of a synbiotic
      mixture capable of modulating the gut microbiota of broiler chickens to obtain an
      increase of the beneficial bacteria (i.e. bifidobacteria, lactobacilli) and a
      competitive reduction of C. jejuni. The prebiotic compound used in the mixture
      was chosen after an in vivo trial: a fructooligosaccharide and a
      galactooligosaccharide were separately administered to broilers mixed with normal
      feed at a concentration of 0.5% and 3%, respectively. Quantitative PCR on DNA
      extracted from fecal samples revealed a significant (p<0.05) increase of
      Bifidobacterium spp. in broilers treated with the galactooligosaccharide, coupled
      to a decrease (p<0.05) of Campylobacter spp. The galactooligosaccharide was then
      combined with a probiotic Bifidobacterium strain (B. longum subsp. longum
      PCB133), possessing in vitro antimicrobial activity against C. jejuni. The strain
      was microencapsulated in a lipid matrix to ensure viability into the feed and
      resistance to stomach transit. Finally, the synbiotic mixture was administered to
      broiler chickens for 14 days mixed with normal feed in order to have an intake of
      10(9)CFU of PCB133/day. Bifidobacterium spp., Lactobacillus spp., Campylobacter
      spp., B. longum subsp. longum and C. jejuni were quantified in fecal samples.
      PCB133 was recovered in feces of all animals. C. jejuni concentration in poultry
      feces was significantly (p<0.05) reduced in chickens administered with the
      synbiotic mixture. This study allowed to highlight the positive effect of the
      synbiotic approach for C. jejuni reduction in broiler chickens, which is of
      fundamental importance for the safety of poultry meat consumers.

PMID- 22608659
TI  - Public health planning for dementia must start now.

PMID- 22608660
TI  - Neurological disorders in the 11th revision of the International Classification
      of Diseases: now open to public feedback.

PMID- 22608661
TI  - Stroke and familial hemiplegic migraine.

PMID- 22608663
TI  - Music therapy's breakthrough act.

PMID- 22608664
TI  - Pierre Gressens: pioneer of perinatal neuroscience.

PMID- 22608666
TI  - Diabetic neuropathy: clinical manifestations and current treatments.
AB  - Diabetic peripheral neuropathy is a prevalent, disabling disorder. The most
      common manifestation is distal symmetrical polyneuropathy (DSP), but many
      patterns of nerve injury can occur. Currently, the only effective treatments are
      glucose control and pain management. While glucose control substantially
      decreases the development of neuropathy in those with type 1 diabetes, the effect
      is probably much smaller in those with type 2 diabetes. Evidence supports the use
      of specific anticonvulsants and antidepressants for pain management in patients
      with diabetic peripheral neuropathy. However, the lack of disease-modifying
      therapies for diabetic DSP makes the identification of new modifiable risk
      factors essential. Growing evidence supports an association between components of
      the metabolic syndrome, including prediabetes, and neuropathy. Studies are needed
      to further explore this association, which has implications for the development
      of new treatments for this common disorder.

PMID- 22608667
TI  - Aquaporin 4 and neuromyelitis optica.
AB  - Neuromyelitis optica is an inflammatory demyelinating disorder of the CNS. The
      discovery of circulating IgG1 antibodies against the astrocyte water channel
      protein aquaporin 4 (AQP4) and the evidence that AQP4-IgG is involved in the
      development of neuromyelitis optica revolutionised our understanding of the
      disease. However, important unanswered questions remain--for example, we do not
      know the cause of AQP4-IgG-negative disease, how astrocyte damage causes
      demyelination, the role of T cells, why peripheral AQP4-expressing organs are
      undamaged, and how circulating AQP4-IgG enters neuromyelitis optica lesions. New
      drug candidates have emerged, such as aquaporumab (non-pathogenic antibody
      blocker of AQP4-IgG binding), sivelestat (neutrophil elastase inhibitor), and
      eculizumab (complement inhibitor). Despite rapid progress, randomised clinical
      trials to test new drugs will be challenging because of the small number of
      individuals with the disorder.

PMID- 22608669
TI  - Tertiary mechanisms of brain damage: a new hope for treatment of cerebral palsy?
AB  - Cerebral palsy is caused by injury or developmental disturbances to the immature
      brain and leads to substantial motor, cognitive, and learning deficits. In
      addition to developmental disruption associated with the initial insult to the
      immature brain, injury processes can persist for many months or years. We suggest
      that these tertiary mechanisms of damage might include persistent inflammation
      and epigenetic changes. We propose that these processes are implicit in
      prevention of endogenous repair and regeneration and predispose patients to
      development of future cognitive dysfunction and sensitisation to further injury.
      We suggest that treatment of tertiary mechanisms of damage might be possible by
      various means, including preventing the repressive effects of microglia and
      astrocyte over-activation, recapitulating developmentally permissive epigenetic
      conditions, and using cell therapies to stimulate repair and regeneration
      Recognition of tertiary mechanisms of damage might be the first step in a complex
      translational task to tailor safe and effective therapies that can be used to
      treat the already developmentally disrupted brain long after an insult.

PMID- 22608670
TI  - Effect of comorbid illness on the long-term outcome of adults suffering major
      traumatic injury: a population-based cohort study.
AB  - BACKGROUND: Few studies have assessed the impact of pre-existing medical
      comorbidities on long-term survival after major trauma. This study investigated
      the influence of comorbidities as measured by the Charlson Comorbidity Index
      (CCI) on the 1-year mortality after major traumatic injury. METHODS: Adult
      patients who survived their initial trauma admission in Calgary, Alberta, Canada,
      between April 1, 2002, and March 31, 2006, defined the study population. Clinical
      and outcome information was obtained from regional electronic databases. RESULTS:
      The study population consisted of 3,080 patients. The median age was 43.3 years
      (interquartile range, 26.9-59.3 y), and the median Injury Severity Score was 20
      (interquartile range, 16-25). A total of 478 patients (15.5%) had at least one
      pre-existing comorbidity. The 1-year mortality rate was 2.7% (83 of 3,080). After
      adjusting for the confounding effects of age, the CCI was independently
      associated with 1-year mortality with an odds ratio of 1.24 (95% confidence
      interval, 1.02-1.51; P = .03) per point on the CCI. A model that included the CCI
      and age accurately predicted 1-year mortality (C-statistic, .83; 95% confidence
      interval, .78-.87; P < .0001). CONCLUSIONS: Comorbid illnesses have an important
      influence on long-term outcomes after major trauma. Whether this represents an
      inherent risk for adverse outcome or an opportunity for enhanced medical co
      management remains to be defined.

PMID- 22608668
TI  - The non-fluent/agrammatic variant of primary progressive aphasia.
AB  - The non-fluent/agrammatic variant of primary progressive aphasia (naPPA) is a
      young-onset neurodegenerative disorder characterised by poor grammatical
      comprehension and expression and a disorder of speech sound production. In an era
      of disease-modifying treatments, the identification of naPPA might be an
      important step in establishing a specific cause of neurodegenerative disease.
      However, difficulties in defining the characteristic language deficits and
      heterogeneity in the anatomical distribution of disease in naPPA have led to
      controversy. Findings from imaging studies have linked an impairment of this
      uniquely human language capacity with disruption of large-scale neural networks
      centred in left inferior frontal and anterior superior temporal regions.
      Accordingly, the pathological burden of disease in naPPA is anatomically focused
      in these regions. Most cases of naPPA are associated with the spectrum of
      pathological changes found in frontotemporal lobar degeneration involving the
      microtubule-associated protein tau. Knowledge of these unique clinical
      pathological associations should advance care for patients with this important
      class of neurodegenerative diseases while supplementing our knowledge of human
      cognitive neuroscience.

PMID- 22608671
TI  - Are residents accurate in their assessments of their own surgical skills?
AB  - BACKGROUND: An appropriate level of awareness of one's own technical skill is
      essential to being an effective self-directed learner. The aim of this study was
      to analyze surgical residents' self-awareness by examining their ability to
      predict and assess their own performance in an objective surgical skills
      examination. METHODS: Surgical residents' (n = 216) pre-examination self
      predicted scores and post-examination self-assessed scores were compared with
      objectively measured scores. Accuracy of score prediction and self-assessment
      were compared with resident demographics (age, gender, year of training, and
      nationality). RESULTS: Post-examination self-assessed scores correlated with
      objectively assessed scores (r = .34; P < .001). Higher year of training, older
      age, and non-European nationality were predictive of accuracy in self-prediction
      and self-assessment. CONCLUSIONS: Demographic variables that predict more
      accurate self-awareness of technical skill have been identified. Surgical
      training programs may use these data to anticipate the trainees who need
      assistance in developing better self-awareness.

PMID- 22608672
TI  - Sleep-disordered breathing in premenopausal women: differences between younger
      (less than 30 years old) and older women.
AB  - OBJECTIVE: To compare clinical manifestations and polysomnographic data of sleep
      disordered breathing (SDB) in younger (less than 30 years old) versus older
      premenopausal women. METHODS: A cohort of 420 premenopausal women diagnosed with
      SDB in a university sleep clinic during a 5-year period underwent systematic
      collection of clinical and polysomnographic variables. RESULTS: One-hundred and
      fifteen (27.4%) women were younger than 30 (mean 24.5 +/- 3.5 years), while 305
      (72.6%) were older than 30 (mean 39.5 +/- 5.7 years). The younger premenopausal
      women had less severe SDB with a trend towards upper-airway resistance syndrome.
      Despite similar daytime consequences, snoring was less common in the younger
      group. Both groups of premenopausal women frequently had insomnia and nasal
      abnormalities or craniofacial-deficiency. CONCLUSION: Recognizing the different
      clinical features and understanding the different polysomnographic presentation
      of SDB in young premenopausal women are crucial to detecting and treating this
      syndrome.

PMID- 22608673
TI  - Protective factors of substance use in youth subcultures.
AB  - Youth subcultures, characterized by a distinctive lifestyle, music preference,
      shared values and behaviors, are associated with substance use. The aim of this
      study was to explore whether protective factors such as parental monitoring,
      parental bonding and parental substance abstinence affect the association between
      subculture affiliation and adolescents' substance use. We used data from 15-year
      old elementary school pupils (N=1380; mean age=15.47; response 79.5%) who
      participated in the Health Behaviour in School Aged Children 2009/2010 study. The
      association between subculture affiliation and substance use (smoking, drinking
      alcohol, drunkenness, and cannabis use) was adjusted for parental monitoring,
      parental bonding and parental substance abstinence for boys and girls separately
      using logistic regression. Adolescents affiliated to one of the selected youth
      subcultures were significantly more likely to use substances than other 15-years
      olds, except for cannabis use in girls. Adjustment for parental monitoring
      reduced the association between subculture affiliation and substance use by 31
      64% in girls and by 10-23% in boys. Adjustment for parental bonding and parental
      substance abstinence led to no changes or minor changes. After adjustments for
      protective factors, subculture affiliation remained significantly associated with
      substance use. The role of protective factors in adolescents with a subculture
      affiliation regarding substance use is rather limited. Our findings imply that
      preventive strategies targeting youth subcultures should take protective factors
      into account and be gender-specific.

PMID- 22608674
TI  - Pyrimidin-2(1H)-ones based inhibitors of Mycobacterium tuberculosis orotate
      phosphoribosyltransferase.
AB  - Tuberculosis (TB) is an ancient human chronic infectious disease caused mainly by
      Mycobacterium tuberculosis. The emergence of strains resistant to first and
      second line anti-TB drugs, associated with the increasing number of TB cases
      among HIV positive subjects, and the large number of individuals infected with
      latent bacilli have urged the development of new strategies to treat TB. Enzymes
      of nucleotide metabolism pathways provide promising molecular targets for the
      development of drugs, aiming at both active and latent TB. The orotate
      phosphoribosyltransferase (OPRT) enzyme catalyzes the synthesis of orotidine 5'
      monophosphate from 5'-phospho-alpha-d-ribose 1'-diphosphate and orotic acid, in
      the de novo pyrimidine synthesis pathway. Based on the kinetic mechanism and
      molecular properties, here we describe the design, selection and synthesis of
      substrate analogs with inhibitory activity of M. tuberculosis OPRT (MtOPRT)
      enzyme. Steady-state kinetic measurements were employed to determine the mode of
      inhibition of commercially available and chemically derived compounds. The 6
      Hydroxy-2-oxo-1,2-dihydropyridine-4-carboxylic acid (6) chemical compound and its
      derivative, 3-Benzylidene-2,6-dioxo-1,2,3,6-tetrahydropyridine-4-carboxylic acid
      (13), showed enzyme inhibition constants in the submicromolar range. Isothermal
      titration calorimetry data indicated that binding of both compounds to MtOPRT
      have negative enthalpy and favorable Gibbs free energy probably due to their high
      complementarity to the enzyme's binding pocket. Improvement of compound 13
      hydrophobic character by addition of an aromatic ring substituent resulted in
      entropic optimization, reflected on a thermodynamic discrimination profile
      characteristic of high affinity ligands. These inhibitors represent lead
      compounds for further development of MtOPRT inhibitors with increased potency,
      which may be tested as anti-TB agents.

PMID- 22608675
TI  - Discovery of a new antileishmanial hit in 8-nitroquinoline series.
AB  - A series of nitrated 2-substituted-quinolines was synthesized and evaluated in
      vitro toward Leishmania donovani promastigotes. In parallel, the in vitro
      cytotoxicity of these molecules was assessed on the murine J774 and human HepG2
      cell lines. Thus, a very promising antileishmanial hit molecule was identified
      (compound 21), displaying an IC(50) value of 6.6 MUM and CC(50) values >= 100
      MUM, conferring quite good selectivity index to this molecule, in comparison with
      3 drug-compounds of reference (amphotericin B, miltefosine and pentamidine).
      Compound 21 also appears as an efficient in vitro antileishmanial molecule
      against both Leishmania infantum promastigotes and the intracellular L. donovani
      amastigotes (respective IC(50) = 7.6 and 6.5 MUM). Moreover, hit quinoline 21
      does not show neither significant antiplasmodial nor antitoxoplasmic in vitro
      activity and though, presents a selective antileishmanial activity. Finally, a
      structure-activity relationships study enabled to define precisely the
      antileishmanial pharmacophore based on this nitroquinoline scaffold: 2-hydroxy-8
      nitroquinoline.

PMID- 22608676
TI  - When the timing is right: Antibiotic timing and infection after cardiac surgery.
AB  - OBJECTIVES: Guidelines recommend antibiotic prophylaxis 60 minutes before skin
      incision; however, it is unclear whether more precise timing would further reduce
      sternal wound infection. Our objectives were to examine the relationship between
      antibiotic timing and infection, test potential efficacy of optimal antibiotic
      timing in preventing infection, and determine whether patient comorbidity is
      related to timing and infection. METHODS: From 1/1/1995-1/1/2008, 28,250 patients
      underwent 28,702 cardiac surgical procedures involving a median sternotomy; 85%
      received only cefuroxime and 15% received only vancomycin prophylaxis.
      Multivariable analysis identified factors associated with infection within each
      phase, and risk-adjusted optimal timing was determined using patient data, risk
      variables, and hypothetical values of antibiotic timing. RESULTS: Prevalence of
      sternal wound infection was 2.0% (489 patients) for cefuroxime and 2.3% (101
      patients) for vancomycin. Minimum prevalence for infection was 1.8% observed when
      cefuroxime was administered 15 minutes before incision; risk increased to 2.2%
      with administration more than 45 minutes before incision and to 2.8% at 60
      minutes before incision. Minimum prevalence of infection in patients who received
      vancomycin was 1.8% observed with initiation 32 minutes before incision; risk
      increased to 2.2% for administration 45 minutes before incision and 3.2% with
      administration 60 minutes before incision. Simulation for optimal timing found
      that it was influenced by phase-specific risk factors. CONCLUSIONS: Refining
      current antibiotic prophylaxis guidelines may lower sternal wound infections.
      Antibiotic administration timing resulting in lowest likelihood for infection
      varied with antibiotic and patient-specific factors. Optimal risk-adjusted timing
      could potentially reduce infections by 9%-31%.

PMID- 22608677
TI  - Redo laparoscopic repair of benign esophageal disease.
AB  - Laparoscopic fundoplication for gastroesophageal reflux disease has been
      associated with excellent symptom control. Compared with medical treatment,
      laparoscopic Nissen fundoplication has shown favorable control of typical reflux
      symptoms. However, in approximately 2% to 17% of patients, surgical treatment
      fails. The role of reoperative repair for reflux disease and the factors that
      contribute to it are examined.

PMID- 22608678
TI  - Sleepiness and fatigue following traumatic brain injury: a clear relationship?

PMID- 22608679
TI  - Diagnostic yield of echocardiography in stroke: should we improve patient
      selection?
AB  - INTRODUCTION: Last year the European Society of Echocardiography published
      recommendations for the use of echocardiography in identifying potential sources
      of embolism as a cause of ischemic stroke in the absence of other cerebrovascular
      diseases. Both transthoracic echocardiography and transesophageal
      echocardiography play a fundamental role in the assessment, diagnosis and
      management of the embolic source. Due in part to the increased longevity of the
      population and improved survival of cardiac patients, we are now seeing a gradual
      increase in the application of echocardiographic studies as a diagnostic test.
      This has led us to critically analyse their performance in detecting various
      pathologies. OBJECTIVE: Our aim was to analyse the diagnostic yield of
      transthoracic echocardiography in patients with cerebrovascular accident in a
      tertiary hospital. MATERIAL AND METHODS: To this end, we retrospectively analysed
      all echocardiographic studies during 2010 requested from the Neurology Department
      with a diagnosis of stroke. We have studied the diagnostic yield of the test and
      its contribution to the etiological diagnosis based on major and minor
      echocardiographic criteria as recommended by the European Society of
      Echocardiography. RESULTS: We found major echocardiographic criteria in 6
      patients (5%) with embolic stroke and in 2 (0.7%) non embolic, P=.005. In view of
      our results, the performance of transthoracic echocardiography in patients with
      embolic stroke has a low diagnostic yield, which leads us to question systematic
      use of this technique.

PMID- 22608680
TI  - [Migraine triggered by laughing as a form of presentation of a Chiari type I
      malformation].

PMID- 22608681
TI  - Assessing methane oxidation under landfill covers and its contribution to the
      above atmospheric CO2 levels: the added value of the isotope (delta13C and
      delta18O CO2; delta13C and deltaD CH4) approach.
AB  - We are presenting here a multi-isotope approach (delta13C and delta18O of CO2;
      delta13C and deltaD of CH4) to assess (i) the level(s) of methane oxidation
      during waste biodegradation and its migration through a landfill cover in Sonzay
      (France), and (ii) its contribution to the atmospheric CO2 levels above the
      surface. The isotope approach is compared to the more conventional mass balance
      approach. Results from the two techniques are comparable and show that the CH4
      oxidation under the landfill cover is heterogenous, with low oxidation
      percentages in samples showing high biogas fluxes, which was expected in clay
      covers presenting fissures, through which CH4 is rapidly transported. At shallow
      depth, more immobile biogas pockets show a higher level of CH4 oxidation by the
      methanotrophic bacteria. delta13C of CO2 samples taken at different heights (from
      below the cover up to 8m above the ground level) were also used to identify and
      assess the relative contributions of its main sources both under the landfill
      cover and in the surrounding atmosphere.

PMID- 22608682
TI  - The costs of household food waste in South Africa.
AB  - Food waste is problematic for a number of reasons, including the loss of a
      potentially valuable food source or resource for use in other processes (e.g.
      energy generation or composting), wasted resources and emissions in the food
      supply chain, and problems associated with the disposal of organic waste to
      landfill. This paper quantifies the household food waste stream in South Africa,
      in order to draw attention to the magnitude of the problem. In addition, it
      estimates the economic (monetary) value of the wasted food, as well as the costs
      associated with disposing putrescible food waste to landfill, in order to
      highlight the associated costs to society. Costs associated with the loss of a
      potentially valuable food source are valued using a weighted average market price
      of the wasted food. Costs associated with the disposal of food waste to landfill
      are quantified based on estimates of the financial and external costs associated
      with landfilling. For household food waste alone, the costs to society associated
      with these two food-waste related problems are estimated at approximately R21.7
      billion (approximately US$2.7 billion) per annum, or 0.82% of South Africa's
      annual GDP. These costs are therefore significant, particularly considering that
      household food waste accounts for less than 4% of total food losses across the
      food supply chain.

PMID- 22608683
TI  - Are metal ion levels a useful trigger for surgical intervention?
AB  - The purpose of this study was to determine if cobalt and chromium ion levels can
      predict soft tissue damage at total hip revision. This study included 90 metal-on
      metal total hip patients with preoperative cobalt and chromium ion levels. Tissue
      damage noted at revision surgery was graded on a 4-point scale. Sensitivity,
      specificity, and predictive values were calculated for various threshold values.
      Receiver operating characteristic analysis was conducted. Using 7 ppb as a
      threshold, cobalt and chromium ion levels had poor sensitivity and specificity
      (Co, 65% and 56%; Cr, 29% and 75%). Positive predictive values for cobalt and
      chromium were only 48% and 26% respectively. The area under the curve was 0.37
      for cobalt and 0.44 for chromium. The length of time to revision significantly
      correlated with tissue damage (P = .001). Ion levels are unreliable predictors of
      periarticular soft tissue damage and should not be used in isolation as surgical
      intervention triggers.

PMID- 22608684
TI  - Highly cross-linked vs conventional polyethylene: no differences in rim notching
      from micromotion on retrieved acetabular liners.
AB  - Previous literature suggested highly cross-linked acetabular liners demonstrated
      notching patterns that may be a point of crack origin and rim failure. We
      examined (1) whether notching patterns and rim cracks existed and demonstrated
      similar morphological properties in retrieved highly cross-linked and non-cross
      linked liners and (2) whether the dimensions of these notches correlated with
      their duration of implantation. We retrieved a series of 14 identical liners out
      to an average of 2.03 years. Liners were microscopically examined and then
      scanned using microcomputed tomography. All liners demonstrated identical
      notching patterns. Microcomputed tomographic scans demonstrated no signs of crack
      initiation or rim failure but were able to accurately quantify the notch
      dimensions. The notching patterns were likely caused by liner-cup micromotion and
      are better characterized as creep deformation because they did not progress
      markedly over longer durations of implantation.

PMID- 22608685
TI  - Is it time to include vancomycin for routine perioperative antibiotic prophylaxis
      in total joint arthroplasty patients?
AB  - In an effort to reduce methicillin-resistant Staphylococcus aureus (MRSA) and
      overall periprosthetic joint infections (PJI), we switched the perioperative
      prophylactic antibiotic during total knee arthroplasty and total hip arthroplasty
      from cefazolin to vancomycin in June 2008. We retrospectively reviewed the total
      and MRSA PJI in 5036 primary total joint arthroplasties, as well as the cure rate
      of PJI from January 2006 to June 2008 (Ancef Period) and June 2008 to December
      2010 (Vanco Period). With vancomycin, total PJI was significantly reduced (1.0%
      0.5%) and MRSA PJI (0.23%-0.07%). Periprosthetic joint infections that occurred
      were more successfully treated with irrigation and debridement only, not
      requiring spacer (76.9% vs 22.2%). The use of vancomycin as the perioperative
      prophylactic antibiotic for primary total joint arthroplasties appeared to be
      effective in decreasing the rate of PJI and may result, when they occur, in
      infections with less virulent organisms.

PMID- 22608686
TI  - Leukocyte esterase reagent strips for the rapid diagnosis of periprosthetic joint
      infection.
AB  - A total of 223 consecutive total hip or total knee arthroplasties were evaluated
      for periprosthetic joint infection (PJI) using leukocyte esterase reagent (LER)
      strips. Fifty-two LER strips were read as positive (23.3%), 106 were read as
      negative (47.5%), and 65 strips (29.2%) were unable to be read secondary to
      debris or blood in the aspiration. Using a synovial fluid white blood cell count
      of greater than 3000 white blood cell per microliter as an indicator of PJI, the
      sensitivity and specificity were 92.9% and 88.8%, respectively. When using
      positive cultures for diagnosis of PJI, sensitivity and specificity were 93.3%
      and 77.0% and 100% and 86.8% for the cases where a reoperation was performed and
      a combination of factors were used to define PJI. Leukocyte esterase reagent
      strips represent a rapid, inexpensive, and sensitive tool for the diagnosis of
      PJI. Their utility is limited, however, by blood or debris in the synovial fluid
      rendering them unreadable in one-third of cases.

PMID- 22608687
TI  - The outcome of sequential repeated tibial tubercle osteotomy performed in 2-stage
      revision arthroplasty for infected total knee arthroplasty.
AB  - Thirteen patients with infected total knee arthroplasty treated by 2-stage
      revision requiring tibial tubercle osteotomy in both stages for extensile
      exposure were retrospectively analyzed. The preoperative mean range of knee
      motion improved from 60 degrees  (range, 30 degrees -90 degrees ) to 94 degrees 
      (range, 70 degrees -120 degrees ) at latest follow-up. The Knee Society knee
      scores and function scores were 39 and 18 preoperatively and 78 and 67 at latest
      follow-up, respectively. Although proximal migration occurred in 3 cases and a
      partial proximal avulsion fracture of the osteotomy segment occurred in 1 case
      after the second-stage reimplantation, radiographic bony union was observed in
      all cases. Sequential repeated tibial tubercle osteotomy can be a useful
      extensile surgical approach in staged revision for infected total knee
      arthroplasty with satisfactory clinical and radiographic outcomes.

PMID- 22608688
TI  - The use of abduction bracing for the prevention of early postoperative
      dislocation after revision total hip arthroplasty.
AB  - One potential strategy to decrease the risk of dislocation after revision total
      hip arthroplasty (THA) is the use of an abduction brace to limit flexion and
      adduction. The purpose of this study was to compare the dislocation rate after
      revision THA between patients treated with or without an abduction brace. Data
      were obtained from 1211 revision THAs performed in 610 women and 518 men who had
      a mean age of 64.7 years (range, 22-95 years) and were followed up for a minimum
      of 90 days. Five hundred two patients were braced, whereas 650 were not. The 90
      day dislocation rate among patients who wore a brace was 5.2% compared with 5.7%
      in the nonbrace group (P = .70). Multivariate regression found no benefit to
      bracing (P = .37), while controlling for factors found to significantly affect
      dislocation rate in this population. Our data do not support the routine use of
      an abduction brace to aid in the prevention of dislocation.

PMID- 22608690
TI  - Serum white blood cell count and differential do not have a role in the diagnosis
      of periprosthetic joint infection.
AB  - Serum white blood cell (WBC) count and neutrophil differential are frequently
      ordered during preoperative workup of suspected cases of periprosthetic joint
      infection (PJI). However, their roles in diagnosis of PJI have remained unclear
      despite previous studies. In this study, preoperative serum WBC and neutrophil
      percentages were retrieved from hospital charts. The diagnostic cutoff point
      determined by receiver operating characteristic curve analysis was 7800 cells/MUL
      with 55% sensitivity and 66% specificity for WBC count, whereas the cutoff value
      for neutrophil percentage was 68% with 52% sensitivity and 75% specificity. Our
      study confirms the long-held belief that serum WBC count and differential has
      minimal role in routine workup of patients with suspected PJI.

PMID- 22608689
TI  - Comparative effectiveness of metal-on-metal and metal-on-polyethylene bearings in
      Medicare total hip arthroplasty patients.
AB  - The purpose of this study was to compare the risk of complication and revision
      total hip arthroplasty (THA) in Medicare THA patients with different bearings.
      Using the 100% Medicare database (2005-2009), the adjusted risk of complication
      and revision THA was calculated for 148,827 THA patients (93,929 metal-on
      polyethylene, 49,646 metal-on-metal, 5252 ceramic-on ceramic). Adjusted risk of
      deep vein thrombosis, dislocation, periprosthetic joint infection (PJI),
      mechanical loosening, periprosthetic fracture, and revision THA at up to 4 years
      postoperatively was compared using Cox regression. After adjusting for patient
      and hospital factors, metal-on-metal bearings were associated with higher risk of
      PJI (P = .001), mechanical loosening (P < .001), and deep vein thrombosis (P =
      .031) than metal-on-polyethylene bearings and higher risk of PJI (P = .014) than
      ceramic-on-ceramic bearings. Overall short-term revision rates did not vary
      significantly across bearing types, consistent with registry data. The benefits
      of hard-on-hard bearings in Medicare patients remain unproven, and further study
      is needed to compare long-term complication and revision rates in Medicare THA
      patients with different bearing types.

PMID- 22608691
TI  - Evidence-based understanding of management perils for metal-on-metal hip
      arthroplasty patients.
AB  - Adverse biological reactions causing failures of metal-on-metal (MoM) hip
      arthroplasty can be local or systemic. Both dose-dependent cytotoxicity of wear
      debris leading to subsequent necrosis of periprosthetic soft tissues and adaptive
      immunity may play an important role in pathogenesis in susceptible patients.
      There appears to be a spectrum of clinical presentations of adverse soft tissue
      reactions, reflecting a complex interplay of implant, surgical, and patient
      factors. A systematic treatment approach is helpful in optimizing evidence-based
      management of MoM patients. Although specialized tests such as metal ion levels
      are a useful diagnostic tool for evaluating MoM hip arthroplasty patients,
      overreliance on any single investigative tool in clinical decision-making process
      should be avoided. Future research focusing on diagnostic tools for detecting
      adverse periprosthetic soft tissue necrosis as well as optimization of MoM
      bearings and modular connections to further diminish wear and corrosion is
      warranted.

PMID- 22608693
TI  - Osteomalacia produced by a hyperphosphaturic tumor.

PMID- 22608692
TI  - Notch signaling and neural connectivity.
AB  - The cell surface receptor Notch contributes to the development of nearly every
      tissue in most metazoans by controlling the fates and differentiation of cells.
      Recent results have now established that Notch also regulates the connectivity of
      the nervous system, and does so at a variety of levels, including specification
      of neuronal identity, division, survival and migration, as well as axon guidance,
      morphogenesis of dendritic arbors and weighting of synapse strength. To these
      ends, Notch engages at least two signal transduction pathways, one that controls
      nuclear gene expression and another that directly targets the cytoskeleton.
      Coordinating the many functions of Notch to produce neural structure is thus a
      pivotal aspect of building and maintaining the nervous system.

PMID- 22608694
TI  - Medical ethics, research and the pharmaceutical industry.

PMID- 22608695
TI  - Epidemiology of canine distemper virus in wild raccoon dogs (Nyctereutes
      procyonoides) from South Korea.
AB  - Raccoon dogs (Nyctereutes procyonoides) are widespread and common in South Korea.
      In 2011, we obtained serum samples from 102 wild raccoon dogs to survey their
      exposure to canine distemper virus (CDV). Forty-five of the 102 animals (44.1%)
      were seropositive. Field cases of canine distemper in wild raccoon dogs from 2010
      to 2011 were investigated. Fourteen cases of CDV infection were identified by a
      commercially available CDV antigen detection kit. These cases were used for virus
      isolation and molecular analysis. Sequence analysis of hemagglutinin genes
      indicated that all viruses isolated belonged to the Asia-2 genotype. H protein
      residues which are related to the receptor and host specificity (residues 530 and
      549) were analyzed. A glutamic acid (E) residue is present at 530 in all
      isolates. At 549, a histidine (H) residue was found in five isolates and tyrosine
      (Y) residue was found in 6 isolates. Our study demonstrated that CDV infection
      was widespread in wild raccoon dogs in South Korea.

PMID- 22608697
TI  - Sighing no longer an option: healthcare professionals and patients help each
      other in a unique learning environment.

PMID- 22608698
TI  - Engaging parents through gaze: speaker selection in three-party interactions in
      maternity clinics.
AB  - OBJECTIVE: Describing and analyzing speaker selection in conversations between
      the health nurse and parents in maternity clinics. METHODS: The data consisted of
      ten video-recorded encounters in maternity clinics. Using conversation analysis,
      we investigated 89 sequences of interaction in which the health nurse asks a
      question that is verbally addressed to both parents. RESULTS: There was an
      observable pattern of selecting mothers as principal respondents by all
      participants of the encounters in maternity clinics. In a few deviant cases,
      fathers were selected as principal respondents. A typical practice of speaker
      selection was the gaze direction of the health nurse towards the recipient
      (usually the mother) at the closure of her question. Various situational elements
      also influenced which one of the parents answered the question. The deviant cases
      in which fathers were selected as principal respondents were mainly explainable
      by the use of the questionnaire designed to facilitate talking about psycho
      social issues connected with the transition to parenthood. CONCLUSION: Particular
      interactional circumstances and practices can break the pattern of selecting
      mothers as respondents to questions addressed to both parents. PRACTICE
      IMPLICATIONS: Fathers could easily be engaged in conversations through gaze. Also
      the questionnaire seems promising in engaging fathers in conversations in
      clinics.

PMID- 22608696
TI  - Decision preparation, satisfaction and regret in a multi-center sample of men
      with newly diagnosed localized prostate cancer.
AB  - OBJECTIVE: To describe relationships between use of the Personal Patient Profile
      Prostate (P3P) decision support system and patient characteristics, and perceived
      preparation for decision making (PrepDM), satisfaction and decisional regret in
      the context of prostate cancer treatment choice. METHODS: 494 men with localized
      prostate cancer (LPC) were randomized to receive the P3P intervention or usual
      care and completed pre-treatment, 1-month and 6-month outcome measures.
      Multivariable linear regression models were fit for each outcome. RESULTS:
      Physician consult visits prior to enrollment, race/ethnicity, and use of clinic
      provided books were significant predictors of perceived PrepDM at 1 month. Prior
      Internet use and PrepDM significantly predicted 6-month decision satisfaction.
      Decisional regret was significantly predicted by demographics, anxiety, PrepDM
      score, and EPIC bowel domain score at 6 months. Use of P3P did not predict any
      outcome. CONCLUSION: While the P3P intervention did not significantly affect the
      outcomes, pre-enrollment information and preparation were strong predictors of
      the 1- and 6-month outcomes. Decision regret was significantly influenced by
      personal characteristics and post-treatment symptoms/side effects. PRACTICE
      IMPLICATIONS: Information received and used between biopsy and the treatment
      options consult visit is likely to make a difference in decision satisfaction.

PMID- 22608699
TI  - Use of blood polymerase chain reaction testing for diagnosis of herpes simplex
      virus infection.
AB  - The use of herpes simplex virus (HSV) polymerase chain reaction for diagnosis of
      HSV disease involving the central nervous system has not translated into
      widespread use for the detection of DNAemia. We report our 6-year experience
      using blood polymerase chain reaction testing for HSV infection in neonates and
      older children with HSV disease.

PMID- 22608700
TI  - Novel ryanodine receptor 2 mutation associated with a severe phenotype of
      catecholaminergic polymorphic ventricular tachycardia.
AB  - An adolescent girl with a history of anxiety associated seizure-like episodes was
      ultimately diagnosed with catecholaminergic polymorphic ventricular tachycardia.
      She tested positive for a novel mutation of the ryanodine receptor. The report
      underscores how genetic arrhythmia syndromes may be mistaken for neurologic
      disorders.

PMID- 22608702
TI  - Retraction: Etiology of rotator cuff tears in paraplegic patients: a case-control
      study.

PMID- 22608701
TI  - Attentional demands of cued walking in healthy young and elderly adults.
AB  - Acoustic and visual cues are frequently used in gait rehabilitation. Attuning the
      steps to the cues is attentionally demanding. We examined the attentional demands
      of walking to two types of cues using a probe reaction time (RT) task. The steps
      were cued by either metronome beeps or visual stepping stones projected on a
      treadmill. The coupling between gait and these cues was assessed using a
      perturbation paradigm. In view of age-related changes in attentional demands of
      motor control, both elderly and young adults were tested. RTs were determined for
      walking to the two types of cues, as well as for three control conditions, viz.
      uncued walking, standing, and sitting. For all conditions, RTs were higher for
      elderly adults. However, the difference between elderly and young adults did not
      vary over conditions. Uncued walking required more attention than did standing
      and sitting. The attentional demands were further elevated during cued walking,
      with larger RTs for walking to visual stepping stones than to metronome beeps.
      Because the coupling to the cues was superior in the stepping stones condition,
      this type of cues seems to aid cued walking by allocating higher levels of
      attention to task-relevant information (viz. future footfall positions). Hence,
      the observed differences between the two cueing types may be associated with the
      natural dependence of gait on visual information.

PMID- 22608703
TI  - Increase in interleukin-8 production from circulating neutrophils upon antibiotic
      therapy in cystic fibrosis patients.
AB  - BACKGROUND: It is not known whether antibiotic therapy for lung disease in cystic
      fibrosis (CF) has an influence on circulating polymorphonuclear neutrophil (PMN)
      function and apoptosis. PATIENTS AND METHODS: Blood PMNs were obtained from 14 CF
      patients before and after antibiotic treatment for an acute exacerbation, and
      from 10 healthy controls. PMNs were evaluated for production of reactive oxygen
      species (ROS) by spectrophotometry, of cytokines in the conditioned medium by
      ELISA, and apoptotic response by cytofluorimetry. RESULTS: ROS and interleukin
      (IL)-8 were produced at higher levels by CF PMNs pre-therapy than control PMNs
      under basal conditions. IL-8 levels further increased after therapy. Early
      apoptotic response was higher in CF PMNs pre-therapy than in control PMNs, and
      this pattern did not change after antibiotic treatment. CONCLUSIONS: Circulating
      PMNs are primed in CF acute patients. Further studies are needed to consider PMN
      produced IL-8 as a biomarker to evaluate response to antibiotic therapy in CF
      patients.

PMID- 22608704
TI  - MRI of congenital and developmental abnormalities of the knee.
AB  - The knee joint is the one of the most common locations for congenital and
      developmental musculoskeletal abnormalities. Initial imaging of the knee joint
      should always begin with conventional radiographs. However, evaluation of the
      bone marrow, cartilaginous, ligamentous, and other soft-tissue components of the
      knee joint are better characterized with magnetic resonance imaging (MRI). We
      present the MRI findings of prevalent congenital and developmental abnormalities
      in the paediatric knee with particular emphasis on the components of the growing
      skeleton.

PMID- 22608705
TI  - Infection level of monogenean gill parasite, Diplozoon kashmirensis (Monogenea,
      Polyopisthocotylea) in the Crucian Carp, Carassius carassius from lake ecosystems
      of an altered water quality: What factors do have an impact on the Diplozoon
      infection?
AB  - Monogeneans are of great interest to the ecologists because of their simple life
      cycle and are considered as one of the important and sensitive parasites to any
      changes in water quality. The monogenean gill parasite, Diplozoon kashmirensis of
      the Carassius carassius was examined with the aim to evaluate the infection level
      and the factors influencing the infection. Our results showed that highest
      prevalence (34.22%) of D. kashmirensis was in the lake having high trophic status
      and least prevalence (10.90%) in the lake having least trophic status. Infection
      levels were significantly higher at the basins/sites having deteriorated water
      quality in comparison to the basins/sites having better water quality. The
      combined effect of pollutants and eutrophication showed decrease in intensity of
      D. kashmirensis in one of the polluted/hypertrophied site in the hypertrophic
      lake (Anchar Lake), while as synergistic effect (i.e. increase) on prevalence and
      intensity was observed in one of the polluted/hypertrophied site in the eutrophic
      lake (Dal Lake). Sex was not an important factor influencing the D. kashmirensis
      in three lakes. The study showed that condition factor was significantly higher
      in the hypertrophic lake and in an uninfected fish. In addition microhabitat
      influenced the Diplozoon infection. Most preferable site for the D. kashmirensis
      was middle sector of the gill. Furthermore, the gill parasite showed
      significantly positive correlation (r(p)=0.6, P<0.05) with water temperature in
      the hypertrophic lake, thus showing the impact of water temperature on this
      parasite. It was concluded that intra lake differences, season, condition factor,
      microhabitat and water temperature influenced the infection of D. kashmirensis.
      It seems from the data that eutrophic and hypertrophic habitats were favourable
      for the D. kashmirensis. The D. kashmirensis showed both antagonistic and
      synergistic response to the combined effect of pollution and eutrophication.

PMID- 22608706
TI  - Introduction to paediatric hepatology.

PMID- 22608707
TI  - An appraisal of soil diffuse contamination in an industrial district in northern
      Italy.
AB  - Soil diffuse contamination is one the major soil threats, especially in regions
      with a high population density and strong industrialization. In this work
      agricultural, natural, and periurban soils of an Italian Province (858 km(2))
      were sampled and analyzed. Overall, 140 samples were taken at two depths and
      analyzed for 10 trace elements, 13 rare earth elements and for organic
      contaminants (PCBs, PCDDs and PAHs). The aim of this work was to obtain an
      appraisal of soil diffuse contamination in a large Italian Province by applying
      and validating available tools to quantify background values and evaluate the
      intensity of contamination. Data were processed, background values estimated, and
      enrichment and contamination factors calculated. For some contaminants the
      results allowed a discrimination between natural or anthropic-derived
      contaminants. Some contaminants revealed clear trends of enrichment in function
      of the land use (in particular for periurban soils). REEs were found to mostly
      derive from parent material. The results obtained in this study show the
      importance of merging the quantification of contaminants with the elaboration of
      indices of contamination. These require an accurate quantification of background
      values to be able to discriminate the anthropic contribution. Enrichment factor
      resulted to be more accurate than contamination factor but it cannot be applied
      to organic contaminants and requires a careful selection of the reference element
      to be adopted. This study revealed that some contaminants - Sb, Sn, Pb, and
      organic contaminants - can be used as tracers of diffuse contamination, and
      should be therefore always included in similar studies.

PMID- 22608709
TI  - The effect of copper ions on the lipid composition of subcellular membranes in
      Hydrilla verticillata.
AB  - The paper studies changes in the content and composition of lipids in the
      membranes of chloroplasts, mitochondria and microsomes of the aquatic plant
      Hydrilla verticillata exposed to copper ions (100 MUM; 1, 3, 6 and 24 h). The
      rate of copper accumulation and the coefficient of its extraction by the plant
      were also determined. The presence of copper in the incubation medium and its
      accumulation in the plant tissues decreased the content of photosynthetic
      pigments, stimulated lipid peroxidation and enhanced membrane permeability. The
      gradual accumulation of copper in the plant tissues was accompanied by specific
      changes in the composition of lipids: the content of sulfolipids (SQDG) in
      chloroplasts declined; the content of monogalactosyl diacylglycerols (MGDG),
      digalactosyl diacylglycerols (DGDG) and phosphatidyl glycerols (PG) in
      chloroplasts and mitochondria grew after an hour of copper exposure; and the
      content of all the lipids except phosphatidic acids (PA) decreased after 3 h of
      exposure. The decline in the content of phosphatidyl cholines (PC) was first
      observed in the membranes of microsomes (after an hour of exposure) and later in
      the membranes of chloroplasts and mitochondria (after 3-6 h of exposure). The
      experiments with incorporation of [2-(14)C]sodium acetate into fatty acids of
      polar lipids showed that in parallel with lipid destruction, there took place an
      intensive and specific renewal of the lipid pool of subcellular membrane
      fractions.

PMID- 22608708
TI  - Nonideal transport of contaminants in heterogeneous porous media: 9 - impact of
      contact time on desorption and elution tailing.
AB  - A series of miscible-displacement experiments was conducted to examine the impact
      of sorption contact time on desorption and elution of trichloroethene from a well
      characterized soil. A large number of contact times were examined, spanning 1h to
      4 years (~2 * 10(6)h). Effluent trichloroethene concentrations were monitored
      over a range of greater than six orders of magnitude, allowing characterization
      of potential asymptotic tailing. The results of the column experiments showed
      that trichloroethene exhibited extensive elution tailing for all experiments.
      Each increase in contact time resulted in a successive increase in the extent of
      tailing. In total, the number of pore volumes of water flushing required to reach
      the analytical detection limit increased from approximately 1000 for the 1-h
      contact time to almost 9000 for the 4-year contact time. These results indicate
      that a contact time of less than 1h produced a sorbed phase that is relatively
      resistant to desorption, and that a progressive increase in resistance to
      desorption occurred with increased contact time. A mathematical model
      incorporating nonlinear, rate-limited sorption/desorption described by a
      continuous-distribution reaction function was used to successfully simulate the
      measured data. The nonlinear sorption, the apparent rapid development of
      desorption resistance, and the progressive increase in resistance with increasing
      contact time are consistent with behavior anticipated for sorbate interactions
      with hard-carbon components of the soil.

PMID- 22608710
TI  - [Reply].

PMID- 22608711
TI  - Paroxysmal supraventricular tachycardia and Wolff-Parkinson-White syndrome in
      ankylosing spondylitis: a large cohort observation study and literature review.
AB  - OBJECTIVES: To investigate the associations of paroxysmal supraventricular
      tachycardia (PSVT) and Wolff-Parkinson-White (WPW) syndrome with ankylosing
      spondylitis (AS). METHODS: We conducted a retrospective cohort study by reviewing
      the medical records of 1503 consecutive AS patients diagnosed at a tertiary
      medical center. The clinical and electrocardiographic (ECG) characteristics of
      641 AS patients having 12-lead ECG available were further analyzed in a precise
      manner. RESULTS: Among the 641 AS patients with 12-lead ECG available for
      detecting cardiac abnormalities, 14 were identified as having PSVT, including 3
      with WPW syndrome and 1 having a WPW (ventricular preexcitation) ECG pattern. A
      higher proportion of AS patients presented with PSVT (21.8/1000) compared with a
      general population-based study (2.25/1000). Also, AS patients demonstrated a
      higher prevalence of WPW syndrome or WPW pattern (6.24/1000) than found in
      general population-based studies (0.9 to 1.5/1000). Ankylosing spondylitis
      patients with PSVT or WPW syndrome had significantly higher rates of peripheral
      arthritis (78.6%; P = 0.002), acute anterior uveitis (64.3%; P = 0.003), bamboo
      spine (64.3%; P = 0.001), and other cardiovascular disorders (85.7%; P < 0.0001)
      than the remaining 627 patients without PSVT. CONCLUSIONS: Ankylosing spondylitis
      patients had a high probability of developing PSVT and WPW syndrome. Detailed ECG
      and electrophysiological examinations are required for early detection of PSVT
      and WPW syndrome for prompt resolution of potentially life-threatening
      complications in all AS patients, especially those presenting with the symptoms
      of palpitation, dizziness, dyspnea, or syncope.

PMID- 22608712
TI  - The contribution of CLIP2 haploinsufficiency to the clinical manifestations of
      the Williams-Beuren syndrome.
AB  - Williams-Beuren syndrome is a rare contiguous gene syndrome, characterized by
      intellectual disability, facial dysmorphisms, connective-tissue abnormalities,
      cardiac defects, structural brain abnormalities, and transient infantile
      hypercalcemia. Genes lying telomeric to RFC2, including CLIP2, GTF2I and
      GTF2IRD1, are currently thought to be the most likely major contributors to the
      typical Williams syndrome cognitive profile, characterized by a better-than
      expected auditory rote-memory ability, a relative sparing of language
      capabilities, and a severe visual-spatial constructive impairment. Atypical
      deletions in the region have helped to establish genotype-phenotype correlations.
      So far, however, hardly any deletions affecting only a single gene in the disease
      region have been described. We present here two healthy siblings with a pure,
      hemizygous deletion of CLIP2. A putative role in the cognitive and behavioral
      abnormalities seen in Williams-Beuren patients has been suggested for this gene
      on the basis of observations in a knock-out mouse model. The presented siblings
      did not show any of the clinical features associated with the syndrome. Cognitive
      testing showed an average IQ for both and no indication of the Williams syndrome
      cognitive profile. This shows that CLIP2 haploinsufficiency by itself does not
      lead to the physical or cognitive characteristics of the Williams-Beuren
      syndrome, nor does it lead to the Williams syndrome cognitive profile. Although
      contribution of CLIP2 to the phenotype cannot be excluded when it is deleted in
      combination with other genes, our results support the hypothesis that GTF2IRD1
      and GTF2I are the main genes causing the cognitive defects associated with
      Williams-Beuren syndrome.

PMID- 22608714
TI  - Characterization of microbial populations associated with natural swimming pools.
AB  - Natural swimming pools are artificially created bodies of water that are intended
      for human recreational bathing and have no chemical disinfection treatment. The
      microbial populations in four private natural swimming pools were analysed to
      assess the typical microbiological parameters, establish the origin of faecal
      contamination in the water, and predict the behaviour of larger systems that are
      open to the public. For this purpose, faecal coliforms, E. coli, enterococci,
      aerobic heterotrophic bacteria and Pseudomonas aeruginosa were enumerated in
      summer and winter. Moreover, faecal coliforms and enterococci populations were
      biochemically phenotyped with the Phene-Plate System, the diversity and
      similarity indexes were calculated and the isolates were identified. Three of the
      four natural pools exceeded the E. coli or enterococci limits stated in the
      recommendations for natural swimming pools. The concentrations of P. aeruginosa
      and aerobic heterotrophic bacteria were acceptable. The results suggest that
      wildlife was an important source of faecal pollution in the pools. Since there is
      a lack of regulations on these systems, and the health risks are higher than in
      conventional swimming pools, further research is needed to establish the
      parameters for ensuring safe bathing in private and public natural swimming
      pools.

PMID- 22608713
TI  - Social stress and depression during pregnancy and in the postnatal period in
      British Pakistani mothers: a cohort study.
AB  - BACKGROUND: Depressive disorders are common and disabling among perinatal women.
      The rates are high in ethnic minority groups. The causes are not known in British
      Pakistani women. The aim of this study was to estimate the rates, correlates and
      maintaining factors of perinatal depression in a Pakistani sample in UK. The
      design used was a cross-sectional two phase population based survey with a
      prospective cohort study. METHODS: All women in 3rd trimester attending antenatal
      clinic were screened with the Edinburgh postnatal depression scale (EPDS). Women
      scoring 12 or more on EPDS and a random sample of low scorers were interviewed
      using the Schedules for Assessment in Neuropsychiatry (SCAN) and the Life Events
      and Difficulties schedule (LEDS). Social support was assessed with the
      Multidimensional Scale for Perceived Social Support (MSPSS). They were reassessed
      6 months after the delivery using the same measures. RESULTS: The weighted
      prevalence of depression was 16.8%. Depressed mothers had more marked non health
      difficulties (housing, financial and marital). They had less social support and
      were socially isolated. Marked social isolation and marked non-health related
      difficulties were independent predictors of depression. Analyses of all the
      possible risk factors, comparing 26 persistent depressed with 27 depression
      resolved group showed significant differences in the MSPSS subscales between the
      two groups. LIMITATIONS: The study lacked inter-rater reliability testing between
      the individuals carrying out diagnostic interviews. The study sample did not
      accurately represent the general population and information about the origins of
      depression in this group of mothers was limited. CONCLUSION: Depression in
      British Pakistani mothers is associated with social isolation, poor social
      support and severe and persistent social difficulties. The findings will have
      implications in planning suitable services for this group.

PMID- 22608715
TI  - Growing single-center experience with lung transplantation using donation after
      cardiac death.
AB  - BACKGROUND: Early experience with lung transplantation (LTx) using organs from
      donors after cardiac death (DCD) has been promising, although widespread adoption
      has been slow because of the perception of diminished organ quality. Some centers
      have even suggested that use of DCD lungs is high risk and have recommended ex
      vivo evaluation before transplantation. We analyzed our growing single-center
      experience with DCD lungs procured and transplanted using protocols established
      for brain-dead donors. METHODS: From August 2004 to July 2011, 605 patients
      underwent LTx, 32 (4.9%) with DCD organs. Standardized donor selection,
      procurement, and preservation protocols established for brain-dead donors were
      applied to DCD organs. Measured outcomes were Kaplan-Meier survival, early graft
      function measured by arterial partial pressure of oxygen/fraction of inspired
      oxygen (PO2/FIO2 ratio [P/F ratio]), airway complications, spirometry, and
      development of bronchiolitis obliterans syndrome (BOS). RESULTS: Survival was 97%
      at 30 days, 91% at 1 year, 91% at 2 years, and 71% at 3 and 4 years. Mean P/F
      ratio at 6 hours and 24 hours was 305 and 332, respectively. One airway
      complication required intervention. Median time to extubation, intensive care
      unit (ICU), and total hospital lengths of stay were 1, 4, and 14 days,
      respectively. At median follow-up of 2.8 years, median forced expiratory volume
      in 1 second, percent of predicted (FEV1%) of the survivors was 59% (range, 27%
      113%), with 16% (5/32) having BOS. CONCLUSIONS: This growing experience suggests
      that recipient survival and early graft function using DCD lungs is excellent and
      has occurred without significant adjustment of procurement, preservation, or
      implantation protocols. Concerns over diminished organ quality are unfounded, and
      use of DCD lungs should be expanded.

PMID- 22608716
TI  - The Society of Thoracic Surgeons General Thoracic Surgery Database: establishing
      generalizability to national lung cancer resection outcomes.
AB  - BACKGROUND: The Society of Thoracic Surgeons General Thoracic Surgery Database
      (GTDB) has demonstrated outstanding results for lung cancer resection. However,
      whether the GTDB results are generalizable nationwide is unknown. The purpose of
      this study was to establish the generalizability of the GTDB by comparing lung
      cancer resection results with those of the Nationwide Inpatient Sample (NIS), the
      largest all-payer inpatient database in the United States. METHODS: From 2002 to
      2008, primary lung cancer resection outcomes were compared between the GTDB (n =
      19,903) and the NIS (n = 246,469). Primary outcomes were the proportion of
      procedures performed nationally that were captured in the GTDB and differences in
      mortality rates and hospital length of stay. Observed differences in patient
      characteristics, operative procedures, and postoperative events were also
      analyzed. RESULTS: Annual GTDB lung cancer resection volume has increased over
      time but only captures an estimated 8% of resections performed nationally. The
      GTDB and NIS databases had similar median patient age (67 vs 68 years) and female
      sex (50% vs 49%), lobectomy was the most common procedure (64.7% vs 79.7%; p <
      0.001), and pneumonectomies were uncommon (6.3% vs 7.2%; p < 0.001). Compared
      with NIS, the GTDB had significantly lower unadjusted discharge mortality rates
      (1.8% vs 3.0%), median length of stay (5.0 vs 7.0 days; p < 0.001), and
      postoperative pulmonary complication rates (18.5% vs 23.6%, p < 0.001).
      CONCLUSIONS: The GTDB represents a small percentage of the lung cancer resections
      performed nationally and reports significantly lower mortality rates and shorter
      hospital length of stay than national results. The GTDB is not broadly
      generalizable. These results establish a benchmark for future GTDB comparisons
      and highlight the importance of increasing participation in the database.

PMID- 22608718
TI  - Measurement of endo-1,4-beta-glucanase.
AB  - Several procedures are available for the measurement of endo-1,4-beta-glucanase
      (EG). Primary methods employ defined oligosaccharides or highly purified
      polysaccharides and measure the rate of hydrolysis of glycosidic bonds using a
      reducing-sugar method. However, these primary methods are not suitable for the
      measurement of EG in crude fermentation broths due to the presence of reducing
      sugars and other enzymes active on these substrates. In such cases, dyed soluble
      or insoluble substrates are preferred as they are specific, sensitive, easy to
      use, and are not affected by other components, such as reducing sugars, in the
      enzyme preparation.

PMID- 22608717
TI  - Cannulation strategy for aortic arch reconstruction using deep hypothermic
      circulatory arrest.
AB  - BACKGROUND: Aortic arch reconstruction in neonates is commonly performed using
      deep hypothermic circulatory arrest. However, concerns have arisen regarding
      potential adverse neurologic outcomes from this complex procedure, raising
      questions about the best arterial cannulation approach for cerebral perfusion and
      effective systemic hypothermia. In this study, we use computational fluid
      dynamics to investigate the effect of different cannulation strategies in
      neonates. METHODS: We used a realistic template of a hypoplastic neonatal aorta
      as the base geometry to investigate four cannulation options: (1) right
      innominate artery, (2) innominate root, (3) patent ductus arteriosus (PDA), or
      (4) innominate root and PDA. Performance was evaluated according to the
      numerically predicted cerebral and systemic flow distributions compared with
      physiologic perfusion under neonatal conditions. RESULTS: The four cannulation
      strategies were associated with different local hemodynamics; however, this did
      not translate into any significant effect on the measured flow distributions. The
      largest difference only represented 0.8% of the cardiac output and was measured
      in the innominate artery, which received 23.2% of the cardiac output in option 3
      vs 24% in option 4. Pulmonary artery snaring benefited all systemic vessels
      uniformly. CONCLUSIONS: Because of the very high vascular resistances in
      neonates, downstream vascular resistances dictated flow distribution to the
      different vascular beds rather than the cannulation strategy, allowing the
      surgical team to choose their method of preference. However, patients with aortic
      coarctation warrant further investigation and will most likely benefit from a 2
      cannulae approach (option 4).

PMID- 22608719
TI  - Biomass conversion determined via fluorescent cellulose decay assay.
AB  - An example of a rapid microtiter plate assay (fluorescence cellulose decay, FCD)
      that determines the conversion of cellulose in a washed biomass substrate is
      reported. The conversion, as verified by HPLC, is shown to correlate to the
      monitored FCD in the assay. The FCD assay activity correlates to the performance
      of multicomponent enzyme mixtures and is thus useful for the biomass industry.
      The development of an optimized setup of the 96-well microtiter plate is
      described, and is used to test a model that shortens the assay incubation time
      from 72 to 24h. A step-by-step procedure of the final assay is described.

PMID- 22608720
TI  - The analysis of saccharification in biomass using an automated high-throughput
      method.
AB  - The recalcitrance of the cell wall to enzymatic hydrolysis represents one of the
      greatest challenges for using biomass to replace the petroleum as a feedstock for
      fuels and chemicals. Cell walls are complex in architecture and composition,
      posing a biochemical challenge for the development of efficient enzymes to
      release the sugars from the polysaccharide components. The complex composition of
      the polymers that constitute the cell wall requires a mixture of enzymes to
      hydrolyze the different glycosidic bonds present in biomass. The improvement of
      the properties of biomass, in turn, requires the screening of large populations
      of plants in order to identify markers associated with saccharification potential
      or pinpoint the genes that regulate recalcitrance. The improvement of both,
      enzymes and biomass together, requires the capacity to deal with large numbers of
      variables in a combinatorial approach. We have developed a high-throughput system
      that allows the determination of cellulolytic activity in a 96-well plate format
      by automatically handling biomass materials, carrying out hydrolytic reactions,
      and determining the release of reducing sugars. This platform consists of a
      purpose-made robot that grinds, formats, and dispenses precise amounts of solids
      into 96-well plates, and a liquid-handling station specifically designed to carry
      out pretreatments, hydrolysis, and the determination of released reducing sugar
      equivalents using a colorimetric assay. These modules can be used individually or
      in combination according to the function needed. Here we show some examples of
      the capabilities of the platforms in terms of enzyme and biomass evaluation, as
      well as combining the robot with off-line analytical tools.

PMID- 22608721
TI  - Studies of enzymatic cleavage of cellulose using polysaccharide analysis by
      carbohydrate gel electrophoresis (PACE).
AB  - With the advent of fast genome analysis, many genes encoding novel putative
      cellulolytic enzymes are being identified in diverse bacterial and fungal
      genomes. The discovery of these genes calls for quick, robust, and reliable
      methods for qualitative and quantitative characterization of the enzymatic
      activities of the encoded proteins. Here, we describe the use of the
      polysaccharide analysis by carbohydrate gel electrophoresis (PACE) method, which
      was previously used, among other applications, to characterize various
      hemicellulose degrading enzymes; for structural elucidation of these
      carbohydrates; and for analysis of products resulting from enzymatic cleavage of
      cellulose. PACE relies on fluorescent labeling of mono-, oligo-, and
      polysaccharides at their reducing end and separation of the labeled carbohydrates
      by polyacrylamide gel electrophoresis. Labeling can be carried out before or
      after enzymatic digestion. PACE is very sensitive and allows analysis of both
      substrate specificities and kinetic properties of cellulolytic enzymes.

PMID- 22608722
TI  - Measuring processivity.
AB  - Natural cellulolytic enzyme systems as well as leading commercial cellulase
      cocktails are dominated by enzymes that degrade cellulose chains in a processive
      manner. Despite the abundance of processivity among natural cellulases, the
      molecular basis as well as the biotechnological implications of this mechanism
      are only partly understood. One of the major limitations lies in the fact that it
      is not straightforward to measure and quantify processivity in what essentially
      are biphasic experimental systems. Here, we describe and discuss both well
      established methods and newer methods for measuring cellulase processivity. In
      addition, we discuss recent insights from studies on chitinases that may help
      direct further studies on processivity in cellulases.

PMID- 22608723
TI  - Distinguishing xyloglucanase activity in endo-beta(1->4)glucanases.
AB  - The ability of beta-glucanases to cleave xyloglucans, a family of highly
      decorated beta-glucans ubiquitous in plant biomass, has traditionally been
      overlooked in functional biochemical studies. An emerging body of data indicates,
      however, that a spectrum of xyloglucan specificity resides in diverse glycoside
      hydrolases from a range of carbohydrate-active enzyme families-including classic
      "cellulase" families. This chapter outlines a series of enzyme kinetic and
      product analysis methods to establish degrees of xyloglucan specificity and modes
      of action of glycosidases emerging from enzyme discovery projects.

PMID- 22608724
TI  - Methods for structural characterization of the products of cellulose- and
      xyloglucan-hydrolyzing enzymes.
AB  - Structural characterization of oligosaccharide products generated by enzymatic
      hydrolysis of plant cell wall polysaccharides provides valuable information about
      the enzyme's activity and substrate specificity. In this chapter, we describe
      some of the chemical, chromatographic, and spectroscopic methods that we
      routinely use to isolate and characterize oligosaccharides formed by enzymatic
      fragmentation of cellulose and xyloglucan. These include techniques to determine
      glycosyl residue and glycosyl linkage compositions by gas chromatography and mass
      spectrometry. We also illustrate the use of electrospray ionization with
      multistage mass spectrometry, matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry, and nuclear magnetic resonance spectroscopy to perform
      detailed structural analysis of these oligosaccharides.

PMID- 22608725
TI  - The crystallization and structural analysis of cellulases (and other glycoside
      hydrolases): strategies and tactics.
AB  - The three-dimensional (3-D) structures of cellulases, and other glycoside
      hydrolases, are a central feature of research in carbohydrate chemistry and
      biochemistry. 3-D structure is used to inform protein engineering campaigns, both
      academic and industrial, which are typically used to improve the stability or
      activity of an enzyme. Examples of classical protein engineering goals include
      higher thermal stability, reduced metal-ion dependency, detergent and protease
      resistance, decreased product inhibition, and altered specificity. 3-D structure
      may also be used to interpret the behavior of enzyme variants that are derived
      from screening or random mutagenesis approaches, with a view to establishing an
      iterative design process. In other areas, 3-D structure is used as one of the
      many tools to probe enzymatic catalysis, typically dovetailing with physical
      organic chemistry approaches to provide complete reaction mechanisms for enzymes
      by visualizing catalytic site interactions at different stages of the reaction.
      Such mechanistic insight is not only fundamentally important, impacting on
      inhibitor and drug design approaches with ramifications way beyond cellulose
      hydrolysis, but also provides the framework for the design of enzyme variants to
      use as biocatalysts for the synthesis of bespoke oligosaccharides. Here we review
      some of the strategies and tactics that may be applied to the X-ray structure
      solution of cellulases (and other carbohydrate-active enzymes). The general
      approach is first to decide why you are doing the work, then to establish correct
      domain boundaries for truncated constructs (typically the catalytic domain only),
      and finally to pursue crystallization of pure, homogeneous, and monodisperse
      protein with appropriate ligand and additive combinations. Cellulase-specific
      strategies are important for the delineation of domain boundaries, while
      glycoside hydrolases generally also present challenges and opportunities for the
      selection and optimization of ligands to both aid crystallization, and also
      provide structural and mechanistic insight. As the many roles for plant cell wall
      degrading enzymes increase, so does the need for rapid high-quality structure
      determination to provide a sound structural foundation for understanding
      mechanism and specificity, and for future protein engineering strategies.

PMID- 22608726
TI  - Visualization of cellobiohydrolase I from Trichoderma reesei moving on
      crystalline cellulose using high-speed atomic force microscopy.
AB  - Cellulases hydrolyze beta-1,4-glucosidic linkages of insoluble cellulose at the
      solid/liquid interface, generating soluble cellooligosaccharides. We describe
      here our method for real-time observation of the behavior of cellulase molecules
      on the substrate, using high-speed atomic force microscopy (HS-AFM). When
      glycoside hydrolase family 7 cellobiohydrolase from Trichoderma reesei (TrCel7A)
      was incubated with crystalline cellulose, many enzyme molecules were observed to
      move unidirectionally on the surface of the substrate by HS-AFM. The velocity of
      the moving molecules of TrCel7A on cellulose I crystals was estimated by means of
      image analysis.

PMID- 22608727
TI  - Small-angle X-ray scattering and crystallography: a winning combination for
      exploring the multimodular organization of cellulolytic macromolecular complexes.
AB  - Small-angle X-ray scattering (SAXS) is an increasingly popular method to obtain
      low-resolution structures of complex macromolecules and their complexes in
      solution, in part due to recent technical and computational advances that make
      this method more and more accessible. However, to obtain unambiguous molecular
      interpretation from SAXS envelopes, the efficient use of and combination with
      additional structural methods are crucial. The multimodular character of
      cellulases and their assemblage in the cellulosome are ideally analyzed by such a
      combination of structural methods. Here, we describe how information from
      different sources can be combined with SAXS to determine the molecular
      organization and we depict the recent advancements and trends that are leading to
      a more comprehensive picture of the molecular architecture of these multimodular
      enzymes and their organization in macro-assemblages such as cellulosomes.

PMID- 22608728
TI  - Quantitative approaches to the analysis of carbohydrate-binding module function.
AB  - Carbohydrate-binding modules (CBMs) are important components of carbohydrate
      active enzymes. Their primary functions are to assist in substrate turnover by
      targeting appended catalytic modules to substrate and concentrating appended
      catalytic modules on the surface of substrate. Presented here are four well
      established methodologies for investigating and quantifying the CBM
      polysaccharide binding relationship. These methods include: (1) the solid state
      depletion assay, (2) affinity gel electrophoresis, (3) UV difference and
      fluorescence spectroscopy, and (4) isothermal titration calorimetry. In addition,
      entropy-driven CBM-crystalline cellulose binding events and differential
      approaches to calculating stoichiometry with polyvalent polysaccharide ligands
      are also discussed.

PMID- 22608729
TI  - In situ detection of cellulose with carbohydrate-binding modules.
AB  - Cellulose is generally found in the context of complex plant cell wall materials
      and mostly in association with other glycans. Cellulose-directed carbohydrate
      binding modules (CBMs) can be readily adapted to a range of methods for the in
      situ imaging of cellulose structures within plant cell walls or other cellulose
      based materials. Protocols for the preparation and selection of plant materials,
      their fixation and processing for preparation of sections for CBM labeling, and
      fluorescence imaging procedures are described. Approaches to direct methods in
      which CBMs are directly coupled to fluorophores and indirect methods in which
      staged incubations with secondary reagents are used for the fluorescence imaging
      of CBM binding to materials are discussed and presented.

PMID- 22608730
TI  - Interactions between family 3 carbohydrate binding modules (CBMs) and
      cellulosomal linker peptides.
AB  - Family 3 carbohydrate-binding modules (CBM3s) are among the most distinctive,
      diverse, and robust. CBM3s, which are numerous components of both free cellulases
      and cellulosomes, bind tightly to crystalline cellulose, and thus play a key role
      in cellulose degradation through their substrate targeting capacity. In addition
      to the accepted cellulose binding surface of the CBM3 molecule, a second type of
      conserved face (the "shallow groove") is retained on the opposite side of the
      molecule in all CBM3 subfamilies, irrespective of the loss or modification of the
      cellulose-binding function. The exact function of this highly conserved shallow
      groove is currently unknown. The cellulosomal system contains many linker
      segments that interconnect the various modules in long polypeptides chains. These
      linkers are varied in length (5-700 residues). The long linkers are commonly
      composed of repeated sequences that are often rich in Ser, Pro, and Thr residues.
      The exact function of the linker segments in the cellulosomal system is currently
      unknown, although they likely play several roles. In this chapter, we document
      the binding interaction between the conserved shallow-groove region of the CBM3s
      with selected cellulosomal linker segments, which may thus induce conformational
      changes in the quaternary structure of the cellulosome. These conformational
      changes would presumably promote changes in the overall arrangement of the
      cellulosomal enzymes, which would in turn serve to enhance cellulosome efficiency
      and degradation of recalcitrant polysaccharide substrates. Here, we describe two
      different methods for determining the interactions between a model CBM3 and
      cellulosomal linker peptides.

PMID- 22608731
TI  - Approaches for improving thermostability characteristics in cellulases.
AB  - Many efforts have been invested to reduce the cost of biofuel production to
      substitute renewable sources of energy for fossil-based fuels. At the forefront
      of these efforts are the initiatives to convert plant-derived cellulosic material
      to biofuels. Although significant improvements have been achieved recently in
      cellulase engineering in both efficiency and cost reduction, complete degradation
      of lignocellulosic material still requires very long periods of time and high
      enzyme loads. Thermostable cellulases offer many advantages in the bioconversion
      process, which include increase in specific activity, higher levels of stability,
      inhibition of microbial growth, increase in mass transfer rate due to lower fluid
      viscosity, and greater flexibility in the bioprocess. Besides rational design
      methods, which require deep understanding of protein structure-function
      relationship, two of the major methods for improvement in specific cellulase
      properties are directed evolution and knowledge-based library design based on
      multiple sequence alignments. In this chapter, we provide protocols for
      constructing and screening of improved thermostable cellulases. Modifications of
      these protocols may also be used for screening for other improved properties of
      cellulases such as pH tolerance, high salt, and more.

PMID- 22608732
TI  - Thermophilic glycosynthases for oligosaccharides synthesis.
AB  - Glycosynthases are engineered glycoside hydrolases that in suitable reaction
      conditions promote the synthesis of oligosaccharides with exquisite
      stereoselectivity and enhanced regioselectivity, if compared to traditional
      chemical methods. This approach was demonstrated to be successful in a number of
      cases including beta-glycosynthases acting at the termini or within an
      oligosaccharide chain (exo- and endo-glycosynthases, respectively) and, more
      recently, alpha-glycosynthases. This led to the production of a vast repertoire
      of products that include poly- and oligosaccharides, glycoconjugates, and
      glycopeptides. These molecules can be used as ligands of glycoside hydrolases,
      for the characterization of therapeutic enzymes, and as leads of drugs for the
      pharmaceutical industry. In this panorama, hyperthermophilic organisms, which
      thrive at temperatures as high as 80 degrees C, which usually impede the growth
      of other living forms, have been used in the development of interesting novel
      glycosynthases. In fact, the extreme stability of these catalysts to extremes of
      pH and high concentrations of organics has allowed the exploration of novel
      reaction conditions, revealing new avenues for enzyme-catalyzed oligosaccharide
      synthesis.

PMID- 22608733
TI  - Engineering cellulase activity into Clostridium acetobutylicum.
AB  - Clostridium acetobutylicum produces substantial amounts of butanol, and an
      engineered cellulolytic strain of the bacterium would be an attractive candidate
      for biofuel production using consolidated bioprocessing. Recent studies have
      shown that this solventogenic bacterium can be used as a host for heterologous
      production and secretion of individual cellulosomal components, termed the
      minicellulosome. Their secretion yields range from 0.3 to 15 mg/L. Nevertheless,
      it appeared that key cellulosomal enzymes such as family GH48 processive enzymes
      and members of the large family of GH9 cellulases probably necessitate specific
      chaperone(s) for translocation and secretion, that is/are absent in the
      solventogenic bacterium. Heterologous secretion of the latter enzymes, however,
      can be obtained by grafting specific combinations of scaffoldin modules at the N
      terminus of these cellulases, which are then used as cargo domains.

PMID- 22608734
TI  - Transformation of Clostridium thermocellum by electroporation.
AB  - In this work, we provide detailed instructions for transformation of Clostridium
      thermocellum by electroporation. In addition, we describe two schemes for genetic
      modification: allelic replacement-where the gene of interest is replaced by an
      antibiotic marker and markerless gene deletion-where the gene of interest is
      removed and the selective markers are recycled. The markerless gene deletion
      technique can also be used for insertion of genes onto the C. thermocellum
      chromosome.

PMID- 22608735
TI  - Genetic and functional genomic approaches for the study of plant cell wall
      degradation in Cellvibrio japonicus.
AB  - Microbial degradation of plant cell walls is a critical contributor to the global
      carbon cycle, and enzymes derived from microbes play a key role in the
      sustainable biofuels industry. Despite its biological and biotechnological
      importance, relatively little is known about how microbes degrade plant cell
      walls. Much of this gap in knowledge has resulted from difficulties in extending
      modern molecular tools to the study of plant cell wall-degrading microbes. The
      bacterium Cellvibrio japonicus has recently emerged as a powerful model system
      for the study of microbial plant cell wall degradation. C. japonicus is unique
      among microbial model systems in that it possesses the ability to carry out the
      complete degradation of plant cell wall polysaccharides. Furthermore, an
      extensive array of genetic and molecular tools exists for functional genomic
      analysis. In this review, we describe progress in the development of methodology
      for the functional genomic study of plant cell wall degradation by this microbe,
      and discuss future directions for research.

PMID- 22608736
TI  - Methods for the isolation of cellulose-degrading microorganisms.
AB  - The biodegradation of lignocellulose, the most abundant organic material in the
      biosphere, is a feature of many aerobic, facultatively anaerobic and obligately
      anaerobic bacteria and fungi. Despite widely recognized difficulties in the
      isolation and cultivation of individual microbial species from complex microbial
      populations and environments, significant progress has been made in recovering
      cellulolytic taxa from a range of ecological niches including the human,
      herbivore, and termite gut, and terrestrial, aquatic, and managed environments.
      Knowledge of cellulose-degrading microbial taxa is of significant importance with
      respect to nutrition, biodegradation, biotechnology, and the carbon-cycle,
      providing insights into the metabolism, physiology, and functional enzyme systems
      of the cellulolytic bacteria and fungi that are responsible for the largest flow
      of carbon in the biosphere. In this chapter, several strategies employed for the
      isolation and cultivation of cellulolytic microorganisms from oxic and anoxic
      environments are described.

PMID- 22608737
TI  - Metagenomic approaches to the discovery of cellulases.
AB  - Most of the microorganisms responsible for nutrient cycling in the environment
      have yet to be cultivated, and this could include those species responsible for
      the degradation of cellulose. Known cellulases are well defined at the protein
      sequence level, but gene variants are difficult to amplify from environmental
      DNA. The identification of novel cellulase genes independent of DNA amplification
      is made possible by adopting a direct metagenome sequencing approach to provide
      genes that can be cloned, expressed, and characterized prior to potential
      exploitation, all in the absence of any information on the species from which
      they originated. In this chapter, emerging strategies and methods that will
      enable the identification of novel cellulase genes and provide an unbiased
      perspective on gene expression in situ are presented.

PMID- 22608738
TI  - Escherichia coli expression, purification, crystallization, and structure
      determination of bacterial cohesin-dockerin complexes.
AB  - Cellulosomes are highly efficient nanomachines that play a fundamental role
      during the anaerobic deconstruction of complex plant cell wall carbohydrates. The
      assembly of these complex nanomachines results from the very tight binding of
      repetitive cohesin modules, located in a noncatalytic molecular scaffold, and
      dockerin domains located at the C-terminus of the enzyme components of the
      cellulosome. The number of enzymes found in a cellulosome varies but may reach
      more than 100 catalytic subunits if cellulosomes are further organized in
      polycellulosomes, through a second type of cohesin-dockerin interaction.
      Structural studies have revealed how the cohesin-dockerin interaction mediates
      cellulosome assembly and cell-surface attachment, while retaining the flexibility
      required to potentiate catalytic synergy within the complex. Methods that might
      be applied for the production, purification, and structure determination of
      cohesin-dockerin complexes are described here.

PMID- 22608739
TI  - Measurements of relative binding of cohesin and dockerin mutants using an
      advanced ELISA technique for high-affinity interactions.
AB  - The cellulosome is a large bacterial extracellular multienzyme complex able to
      degrade crystalline cellulosic substrates. The complex contains catalytic and
      noncatalytic subunits, interconnected by high-affinity cohesin-dockerin
      interactions. In this chapter, we introduce an optimized method for comparative
      binding among different cohesins or cohesin mutants to the dockerin partner. This
      assay offers advantages over other methods (such as ELISA, cELIA, SPR, and ITC)
      for particularly high-affinity binding interactions. In this approach, the high
      affinity interaction of interest occurs in the liquid phase during the
      equilibrated binding step, whereas the interaction with the immobilized phase is
      used only for detection of the unbound dockerins that remain in the solution
      phase. Once equilibrium conditions are reached, the change in free energy of
      binding (DeltaDeltaG(binding)), as well as the affinity constant of mutants, can
      be estimated against the known affinity constant of the wild-type interaction. In
      light of the above, we propose this method as a preferred alternative for the
      relative quantification of high-affinity protein interactions.

PMID- 22608740
TI  - Designer cellulosomes for enhanced hydrolysis of cellulosic substrates.
AB  - During the past several years, major progress has been accomplished in the
      production of "designer cellulosomes," artificial enzymatic complexes that were
      demonstrated to efficiently degrade crystalline cellulose. This progress is part
      of a global attempt to promote biomass waste solutions and biofuel production. In
      designer cellulosomes, each enzyme is equipped with a dockerin module that
      interacts specifically with one of the cohesin modules of the chimeric
      scaffoldin. Artificial scaffoldins serve as docking backbones and contain a
      cellulose-specific carbohydrate-binding module that directs the enzymatic complex
      to the cellulosic substrate, and one or more cohesin modules from different
      natural cellulosomal species, each exhibiting a different specificity, that
      allows the specific incorporation of the desired matching dockerin-bearing
      enzymes. With natural cellulosomal components, the insertion of the enzymes in
      the scaffold would presumably be random, and we would not be able to control the
      contents of the resulting artificial cellulosome. There are an increasing number
      of papers describing the production of designer cellulosomes either in vitro, ex
      vivo, or in vivo. These types of studies are particularly intricate, and a number
      of such publications are less meaningful in the final analysis, as important
      controls are frequently excluded. In this chapter, we hope to give a complete
      overview of the methodologies essential for designing and examining cellulosome
      complexes.

PMID- 22608741
TI  - High-throughput screening of cohesin mutant libraries on cellulose microarrays.
AB  - The specificity of cohesin-dockerin interactions is critically important for the
      assembly of cellulosomal enzymes into the multienzyme cellulolytic complex
      (cellulosome). In order to investigate the origins of the observed specificity, a
      variety of selected amino acid positions at the cohesin-dockerin interface can be
      subjected to mutagenesis, and a library of mutants can be constructed. In this
      chapter, we describe a protein-protein microarray technique based on the high
      affinity of a carbohydrate-binding module (CBM), attached to mutant cohesins.
      Using cellulose-coated glass slides, libraries of mutants can be screened for
      binding to complementary partners. The advantages of this tool are that crude
      cell lysate can be used without additional purification, and the microarray can
      be used for screening both large libraries as initial scanning for "positive"
      plates, and for small libraries, wherein individual colonies are printed on the
      slide. Since the time-consuming step of purifying proteins can be circumvented,
      the approach is also appropriate for providing molecular insight into the
      multicomponent organization of complex cellulosomes.

PMID- 22608742
TI  - Methods in Enzymology. Preface.

PMID- 22608743
TI  - beta-Catenin signaling contributes to platelet derived growth factor elicited
      bladder smooth muscle cell contraction through up-regulation of Cx43 expression.
AB  - PURPOSE: Increased gap junctions contribute to bladder overactivity but the
      factors and mechanisms involved in gap junction regulation in the bladder are not
      well established. We examined whether and how platelet derived growth factor
      regulates connexin43 in bladder smooth muscle cells. MATERIALS AND METHODS:
      Cultured rat bladder smooth muscle cells were treated with growth factors with or
      without agents that interfere with phosphatidylinositol 3-kinase, mitogen
      activated protein kinase and beta-catenin signaling pathways. Connexin43
      expression was examined by Western and Northern blot, and immunochemistry.
      Functional gap junctions were evaluated by scrape-loading dye transfer assay.
      Bladder smooth muscle cell contraction was measured by collagen gel contraction.
      RESULTS: 1) Platelet derived growth factor induced phosphatidylinositol 3-kinase
      and mitogen activated protein kinase dependent accumulation of nuclear beta
      catenin. This was followed by increased connexin43 expression. 2) Down-regulation
      of beta-catenin by specific siRNA abolished the connexin43 increasing effect of
      platelet derived growth factor while beta-catenin stimulation due to glycogen
      synthase kinase inhibition mimicked that effect. 3) Basic fibroblast growth
      factor and epidermal growth factor also induced connexin43 expression. Their
      effects were potentiated by platelet derived growth factor. 4) Gap junction
      inhibition attenuated the bladder smooth muscle cell contraction induced by
      platelet derived growth factor. Consistently fibroblasts from connexin43 knockout
      (Cx43-/-) mice showed a much weaker contractile response to platelet derived
      growth factor than cells from connexin43-wild (Cx43+/+) litter mates.
      CONCLUSIONS: Platelet derived growth factor induces connexin43 expression and
      bladder smooth muscle cell contraction by activating beta-catenin signaling. As a
      convergence point for many signal pathways, beta-catenin may be targeted to treat
      bladder overactivity.

PMID- 22608744
TI  - Gene expression profiles of prostate cancer stem cells isolated by aldehyde
      dehydrogenase activity assay.
AB  - PURPOSE: Prostate cancer cells include a small population of cancer stem
      like/cancer initiating cells, which have roles in cancer initiation and
      progression. Recently aldehyde dehydrogenase activity was used to isolate stem
      cells of various cancer and normal cells. We evaluated the aldehyde dehydrogenase
      activity of the human prostate cancer cell line 22Rv1 (ATCC(r)) with the
      ALDEFLUOR(r) assay and determined its potency as prostate cancer stem-like/cancer
      initiating cells. MATERIALS AND METHODS: The human prostate cancer cell line
      22Rv1 was labeled with ALDEFLUOR reagent and analyzed by flow cytometry.
      ALDH1(high) and ALDH1(low) cells were isolated and tumorigenicity was evaluated
      by xenograft transplantation into NOD/SCID mice. Tumor sphere forming ability was
      evaluated by culturing in a floating condition. Invasion capability was evaluated
      by the MatrigelTM invasion assay. Gene expression profiling was assessed by
      microarrays and reverse transcriptase-polymerase chain reaction. RESULTS:
      ALDH1(high) cells were detected in 6.8% of 22Rv1 cells, which showed
      significantly higher tumorigenicity than ALDH1(low) cells in NOD/SCID mice (p <
      0.05). Gene expression profiling revealed higher expression of the stem cell
      related genes PROM1 and NKX3-1 in ALDH1(high) cells than in ALDH1(low) cells.
      ALDH1(high) cells also showed higher invasive capability and sphere forming
      capability than ALDH1(low) cells. CONCLUSIONS: Results indicate that cancer stem
      like/cancer initiating cells are enriched in the ALDH1(high) population of the
      prostate cancer cell line 22Rv1. This approach may provide a breakthrough to
      further clarify prostate cancer stem-like/cancer initiating cells. To our
      knowledge this is the first report of cancer stem-like/cancer initiating cells of
      22Rv1 using the aldehyde dehydrogenase activity assay.

PMID- 22608745
TI  - Re: Long-term outcomes of percutaneous nephrolithotomy in 177 patients with
      chronic kidney disease: a single center experience: T. Akman,M. Binbay, R. Aslan,
      E. Yuruk, F. Ozgor, E. Tekinarslan, O. Yazici, Y. Berberoglu And A. Y.
      Muslumanoglu J Urol 2012; 187: 173-177.

PMID- 22608746
TI  - G Protein beta3 subunit gene C825T polymorphism and its association with the
      presence and clinicopathological characteristics of prostate cancer.
AB  - PURPOSE: A C825T polymorphism in the GNB3 gene encodes the Gbeta3 subunit of
      heterotrimeric G proteins. Due to increased G protein activation the GNB3 825T
      allele, a truncated form of the G3 protein, is associated with enhanced signal
      transduction capacity. This splice variant is associated with various malignant
      diseases. We investigated the possible association of GNB3 gene polymorphism with
      prostate cancer and its clinicopathological characteristics. MATERIALS AND
      METHODS: Using polymerase chain reaction and restriction fragment length
      polymorphism the allele frequency of the C825T polymorphism was investigated in
      172 patients with prostate cancer. Results were compared with those of 344 age
      matched, healthy blood donors. RESULTS: The frequency of the GNB3 825T allele in
      patients with prostate cancer was significantly higher than in controls (49.1% vs
      42.7%, OR 3.76, p = 0.003). Patients with prostate cancer who had the TT genotype
      were at 2.52 times higher risk for prostate cancer than the CC genotype referent
      group (OR 2.22, 95% CI 1.18-4.22, p = 0.008). Accordingly a significant increased
      risk of advanced disease was observed in men carrying the GNB3 TT genotype
      compared with those homozygous for the wild-type C allele (OR 6.24, 95% CI 4.16
      12.45, p = 0.001). Men lacking the C825 allele were at approximately sevenfold
      higher risk for high grade (Gleason score greater than 7) prostate cancer than
      men with the GNB3 CC genotype. CONCLUSIONS: Our study presents preliminary but
      intriguing data suggesting that GNB3 gene polymorphism influences susceptibility
      to prostate cancer.

PMID- 22608747
TI  - Bladder lymphoma.

PMID- 22608749
TI  - Androgen receptor signaling regulates cell growth and vulnerability to
      doxorubicin in bladder cancer.
AB  - PURPOSE: There are several reports of androgen receptor in bladder cancer cases
      but androgen receptor expression and the function of androgen/androgen receptor
      signaling in bladder cancer remain unclear. We investigated androgen receptor
      expression and the role of androgen/androgen receptor signaling in bladder
      cancer. MATERIALS AND METHODS: We evaluated AR mRNA expression in bladder cancer
      tissue by quantitative real-time polymerase chain reaction. The role of androgen
      receptor in cell growth and drug sensitivity was also evaluated in vitro and in
      vivo in several bladder cancer cell lines. RESULTS: AR mRNA expression inversely
      correlated with bladder cancer grade, stage and spread. Of several bladder cancer
      cell lines UMUC3 and MBT-2 markedly expressed androgen receptor transcript and
      protein. In each cell line androgen/androgen receptor signaling blockade using
      androgen deprivation, blockade knockdown and antiandrogen agents decreased cell
      growth, colony formation and cell viability. Androgen receptor expression was
      implicated in doxorubicin resistance. Inversely androgen receptor deprivation and
      knockdown made UMUC3 cells sensitive to doxorubicin. Finally, castration slightly
      suppressed UMUC3 tumor growth in vivo, although this did not attain statistical
      significance. CONCLUSIONS: AR transcript expression inversely correlates with
      bladder cancer clinicopathological characteristics. Androgen/androgen receptor
      signaling has an important role in the growth and vulnerability to doxorubicin of
      bladder cancer cells that express androgen receptor. Androgen/androgen receptor
      signaling might be a possible prophylactic and therapeutic target for bladder
      cancer that shows androgen receptor expression.

PMID- 22608750
TI  - Methyltransferase inhibitor adenosine dialdehyde suppresses androgen receptor
      expression and prostate cancer growth.
AB  - PURPOSE: Although most prostate cancers regress after androgen deprivation
      therapy is given at diagnosis, they eventually regrow in a castration resistant
      manner, spread systemically and end fatally. Thus, novel therapeutic compounds
      are needed for prostate cancer. We previously reported that methylation at
      histone H3 lysine 9 was increased in prostate cancer. In this study we examined
      the effects of the methyltransferase inhibitor adenosine dialdehyde (Sigma(r)) on
      the methylation state of histone H3 lysine 9 and AR gene expression as well as
      its possible usefulness for prostate cancer. MATERIALS AND METHODS: The effect of
      adenosine dialdehyde on the methylation state of histone H3 lysine 9 and AR gene
      expression was examined by quantitative real-time polymerase chain reaction and
      Western blot. We compared methylation at histone H3 lysine 9 at the AR promoter
      region between androgen dependent and castration resistant prostate cancer by
      chromatin immunoprecipitation assay. The cytotoxic effect of adenosine dialdehyde
      on prostate cancer was also evaluated in vitro and in vivo. RESULTS: Adenosine
      dialdehyde suppressed the monomethylation and dimethylation of histone H3 lysine
      9 and inhibited Twist1 as well as androgen receptor expression, which are
      critical for the survival and growth of androgen dependent, androgen sensitive
      and castration resistant prostate cancer cells in which monomethylated histone H3
      lysine 9 increased at the 5' untranslated region of the AR gene. As a result,
      adenosine dialdehyde had a cytotoxic effect on androgen dependent, androgen
      sensitive and castration resistant prostate cancer cells in vitro. Adenosine
      dialdehyde also suppressed prostate cancer growth in vivo in a mouse xenograft
      model. CONCLUSIONS: Results indicate that the methyltransferase inhibitor
      adenosine dialdehyde is a promising, novel therapeutic compound for prostate
      cancer.

PMID- 22608751
TI  - Impact of biological gender and soluble guanylate cyclase stimulation on renal
      recovery after relief of unilateral ureteral obstruction.
AB  - PURPOSE: Gender difference and nitric oxide deficiency contribute to the
      progression of many chronic kidney diseases. In a model of unilateral ureteral
      obstruction relief we analyzed the impact of biological gender and nitric
      oxide/cyclic guanosine monophosphate signaling stimulation on renal disease
      severity and restoration. MATERIALS AND METHODS: Female and male rats underwent
      sham surgery or unilateral ureteral obstruction. After 5-day unilateral ureteral
      obstruction female and male rats were assigned to obstruction relief alone or
      obstruction relief plus 7-day treatment with the soluble guanylate cyclase
      stimulator BAY 41-8543. RESULTS: Compared to male rats with obstruction relief
      renal disease was less severe in female rats, which had significantly less
      tubulointerstitial matrix accumulation and tubular atrophy. In each gender group
      alpha1 and beta1-soluble guanylate cyclase was comparably and significantly
      increased but female rats produced significantly more cyclic guanosine
      monophosphate after treatment with the soluble guanylate cyclase stimulator. In
      each group BAY 41-8543 treatment was associated with significant amelioration of
      renal matrix protein expansion, macrophage infiltration, tubular apoptosis and
      atrophy. CONCLUSIONS: Female gender is protective for unilateral ureteral
      obstruction relief. This was linked to higher sensitivity of the soluble
      guanylate cyclase enzyme and cyclic guanosine monophosphate production in
      response to BAY 41-8543. In these female and male rats enhancing the signaling of
      nitric oxide/cyclic guanosine monophosphate with BAY 41-8543 significantly
      accelerated the restoration of renal architecture after obstruction relief and
      largely ameliorated the differences in disease severity due to the gender
      disparity.

PMID- 22608753
TI  - Factors predicting improvement of renal function after pyeloplasty in pediatric
      patients: a prospective study.
AB  - PURPOSE: We assessed the specific preoperative sonographic and urinary factors
      that may be important in predicting renal function outcomes after pyeloplasty.
      MATERIALS AND METHODS: We prospectively studied 52 consecutive patients with
      ureteropelvic junction obstruction who underwent pyeloplasty at our tertiary care
      center between September 2009 and January 2011. Mean +/- 2 SD patient age was
      4.26 years (range 3 months to 18 years), and minimum followup was 6 months.
      Preoperative ultrasound findings recorded were pelvic anteroposterior diameter,
      pelvic cortical thickness, pelvic volume and pelvic cortical ratio. Spot urine
      protein-to-creatinine ratio from the renal pelvis and bladder was measured
      intraoperatively. Based on changes in differential renal function on diuretic
      renogram, patients were divided into 3 groups. Group 1 had stable differential
      renal function with less than 5% change, group 2 had improved differential renal
      function greater than 5% and group 3 had deterioration of differential renal
      function greater than 5%. Data were analyzed using SPSS(r), version 17 with cross
      tabulation, nonparametric tests and logistic regression. RESULTS: On ultrasound
      only anteroposterior diameter (p = 0.018) and pelvic cortical ratio (p = 0.038)
      were significantly different among the 3 groups. Difference in bladder sample
      protein-to-creatinine ratio was not significant (p = 0.69), while pelvic urine
      protein-to-creatinine ratio was significant (p = 0.001). Anteroposterior
      diameter, pelvic protein-to-creatinine ratio and pelvic cortical ratio were less
      than 50 mm, 0.5 and 15, respectively, in all patients with improved renal
      function. CONCLUSIONS: Sonographic and urinary biochemical parameters may predict
      improvement in renal function after pyeloplasty. Pelvic anteroposterior diameter,
      pelvic cortical ratio and pelvic urine protein-to-creatinine ratio are the most
      useful parameters.

PMID- 22608754
TI  - Re: Delay of surgery in men with low risk prostate cancer: D. O'Brien, S. Loeb,
      G. F. Carvalhal, B. B. McGuire, D. Kan, M. D. Hofer, J. T. Casey, B. T. Helfand
      and W. J. Catalona J Urol 2011; 185: 2143-2147.

PMID- 22608756
TI  - Re: Automated Renal Stone Volume Measurement by Noncontrast Computerized
      Tomography is More Reproducible than Manual Linear Size Measurement: S. R. Patel,
      P. Stanton, N. Zelinski, E. J. Borman, M. A. Pozniak, S. Y. Nakada and P. J.
      Pickhardt J Urol 2011; 186: 2275-2279.

PMID- 22608757
TI  - Renal lymphoma presenting as an incidental renal mass.

PMID- 22608758
TI  - Re: Laparoscopic partial nephrectomy for completely intraparenchymal tumors: B.
      I. Chung, U. J. Lee, K. Kamoi, D. A. Canes, M. Aron and I. S. Gill J Urol 2011;
      186: 2182-2187.

PMID- 22608759
TI  - Effects of alpha particle radiation on gene expression in human pulmonary
      epithelial cells.
AB  - The general public receives approximately half of its exposure to natural
      radiation through alpha (alpha)-particles from radon ((222)Rn) gas and its decay
      progeny. Epidemiological studies have found a positive correlation between
      exposure to (222)Rn and lung carcinogenesis. An understanding of the
      transcriptional responses involved in these effects remains limited. In this
      study, genomic technology was employed to mine for subtle changes in gene
      expression that may be representative of an altered physiological state. Human
      lung epithelial cells were exposed to 0, 0.03, 0.3 and 0.9Gy of alpha-particle
      radiation. Microarray analysis was employed to determine transcript expression
      levels 4h and 24h after exposure. A total of 590 genes were shown to be
      differentially expressed in the alpha-particle radiated samples (false discovery
      rate (FDR)<=0.05). Sub-set of these transcripts were time-responsive, dose
      responsive and both time- and dose-responsive. Pathway analysis showed functions
      related to cell cycle arrest, and DNA replication, recombination and repair
      (FDR<=0.05). The canonical pathways associated with these genes were in relation
      to pyrimidine metabolism, G2/M damage checkpoint regulation and p53 signaling
      (FDR<=0.05). Overall, this gene expression profile suggests that alpha-particle
      radiation inhibits DNA synthesis and subsequent mitosis, and causes cell cycle
      arrest.

PMID- 22608760
TI  - The sleep phenotypes of attention deficit hyperactivity disorder: the role of
      arousal during sleep and implications for treatment.
AB  - About 25-50% of children and adolescents with attention-deficit hyperactivity
      disorder (ADHD) experience sleep problems. An appropriate assessment and
      treatment of such problems might improve the quality of life in such patients and
      reduce both the severity of ADHD and the impairment it causes. According to data
      in the literature and to the overall complexity of the interaction between ADHD
      and sleep, five sleep phenotypes may be identified in ADHD: (i) a sleep phenotype
      characterized mainly by a hypo-arousal state, resembling narcolepsy, which may be
      considered a "primary" form of ADHD (i.e. without the interference of other sleep
      disorders); (ii) a phenotype associated with delayed sleep onset latency and with
      a higher risk of bipolar disorder; (iii) a phenotype associated with sleep
      disordered breathing (SDB); (iv) another phenotype related to restless legs
      syndrome (RLS) and/or periodic limb movements; (v) lastly, a phenotype related to
      epilepsy/or EEG interictal discharges. Each sleep phenotype is characterized by
      peculiar sleep alterations expressed by either an increased or decreased level of
      arousal during sleep that have important treatment implications. Treatment with
      stimulants is recommended above all in the primary form of ADHD, whereas
      treatment of the main sleep disorders or of co-morbidities (i.e. bipolar
      disorders and epilepsy) is preferred in the other sleep phenotypes. All the sleep
      phenotypes, except the primary form of ADHD and those related to focal benign
      epilepsy or focal EEG discharges, are associated with an increased level of
      arousal during sleep. Recent studies have demonstrated that both an increase and
      a decrease in arousal are ascribable to executive dysfunctions controlled by
      prefrontal cortical regions (the main cortical areas implicated in the
      pathogenesis of ADHD), and that the arousal system, which may be hyperactivated
      or hypoactivated depending on the form of ADHD/sleep phenotype.

PMID- 22608761
TI  - Design, synthesis and antiviral activity of novel pyridazines.
AB  - A series of pyridazines were prepared and evaluated for their anti-HIV activity.
      The new synthetic route involving a novel rearrangement reaction provided a
      practical method for the preparation of 5-hydroxypyridazines. The primary
      bioassay results indicated that most of the pyridazines possess anti-HIV
      activity. It ought to been mentioned that the rearranged compounds 35 and 39
      exhibited relatively higher HIV inhibitory effect. Most of the synthesized
      compounds were also found to possess good anti-TMV activity, of which compound 9
      showed similar in vivo anti-TMV activity to commercial plant virucide Ribavirin.
      This work provides a new and efficient approach to evolve novel multi-functional
      antiviral agents by rational integration and optimization of previously reported
      antiviral agents.

PMID- 22608762
TI  - Synthesis and antidepressant activity of arylalkanol-piperidine derivatives as
      triple reuptake inhibitors.
AB  - A series of arylalkanol-piperidine derivatives was synthesized, and their triple
      reuptake inhibition and in vivo activities have been evaluated. Among them,
      compounds 2a, 2j, 2k, 2m and 2n exhibited high potency for 5-HT, NA and DA
      transporters. Optimized compounds 2j and 2m showed significant reduction of
      immobility time compared to that of vehicle in the mouse tail suspension test
      (TST) test at doses ranging from 10 to 50 mg/kg po, and were not generally motor
      stimulants at 50 mg/kg dose. In addition, compounds 2j and 2m displayed desirable
      pharmacokinetic properties in SD rats.

PMID- 22608763
TI  - Contemporary issues in the training of UK health and social care professionals-
      Looking after people with a learning disability.
AB  - The health and social care of people labelled with 'learning disability' has
      historically been a disputed territory for those individuals working within the
      nursing and allied health professions. In recent times this situation has seen
      public debate as instances of poor care and avoidable deaths have received a high
      profile in the popular and professional presses. Here we report on a local
      initiative where students can study for a joint honours award which allows them
      to practise as a generic social worker and a learning disability nurse. We
      believe that the inter-professional perspective improves their ability to manage
      the increasingly complex aspects of health and social care that this client group
      demands. Furthermore, we suggest that if a similar model were to be applied at a
      foundation module level to the training of ALL health and social care
      professionals, then the results would be a win/win situation for all parties.
      This would also go some way to meeting the recommendations of Sir Jonathan
      Michael's report, Health Care for All (DH, 2008).

PMID- 22608764
TI  - Developing as a scholarly writer: the experience of students enrolled in a PhD in
      nursing program in the United States.
AB  - Graduates of doctoral nursing programs are expected to disseminate knowledge
      through scholarly writing, yet faculty teaching doctoral nursing students in two
      specific programs in western Pennsylvania in the United States noted students
      enter their doctoral programs with varying writing skills. The purpose of this
      hermeneutic phenomenological study was to uncover the lived experience of
      developing as a scholarly writer. Data were collected through the use of a
      demographic questionnaire and personal interviews with 10 students enrolled in
      their first semester of coursework in a traditional, rather than online, 60
      credit PhD in nursing program at a large state university in western
      Pennsylvania. All interviews were recorded and transcribed and served as rich
      data sources. Data were analyzed using a systematic approach consistent with
      hermeneutic phenomenology. Themes uncovered included (a) coming to know about
      scholarly writing, (b) shifting thinking in order to write scholarly, (c) giving
      birth: the pain and the pleasure of scholarly writing, and (d) putting all the
      pieces together into the final product. Findings from this study can help faculty
      to understand the experiences of nursing student scholarly writing development.
      Recommendations based on the findings include a collection of teaching strategies
      that can be used to facilitate scholarly writer development across all levels of
      nursing education.

PMID- 22608766
TI  - Highly-sensitive electrochemical immunosensing method based on dual amplification
      systems.
AB  - In this work, a novel immunosensing method has been developed on the basis of the
      sensitive determination of a product generated by an enzyme reaction with dual
      amplification system combining an electrochemical-redox cycling and coulometric
      signal transduction using a galvanic cell. Analytes were captured on
      microparticles to form sandwich-type immunocomplexes and then labeled with beta
      galactosidase (beta-gal). 4-Aminophenol (PAP) produced by enzyme reaction of beta
      gal was introduced into the anode compartment consisting of a comb type of an
      interdigitated array (IDA) electrode. PAP was oxidized at the IDA electrode by
      the coupled reduction of silver ions at the glassy carbon (GC) electrode of the
      cathode, resulting in the deposition of silver metal on the GC electrode. The
      other comb of the IDA electrode was used to reduce quinoneimine generated by the
      oxidation of PAP, regenerating PAP. The deposited silver was collectively
      converted to a signal by anodic stripping voltammetry. The amount of silver
      deposited corresponded to the degree of PAP oxidation by redox cycling, which
      leads to an enhancement of the stripping signal due to the conversion of the
      product (PAP) and accumulation of the insoluble silver metal. Using
      carcinoembryonic antigen as a model analyte, the present immunosensing method
      showed linear behavior over two orders of magnitude with detection limits down to
      0.01 ng/mL. Dual signal amplification with redox cycling and coulometric signal
      transduction provides a promising, sensitive, and simple method for the
      determination of marker proteins.

PMID- 22608765
TI  - Comparison of sensing strategies in SPR biosensor for rapid and sensitive
      enumeration of bacteria.
AB  - Rapid and sensitive detections of microorganisms are very important for
      biodefence, food safety, medical diagnosis and pharmaceutics. The present study
      aims to find out the most proper bioactive surface preparation method to develop
      rapid, sensitive and selective bacteria biosensor, based on surface plasmon
      resonance (SPR) spectroscopy. Escherichia coli (E. coli) was used as a model
      bacterium and four sensing strategies in SPR were tested. Three of these
      strategies are antibody immobilization methods that are non-specific adsorption,
      specific adsorption via the avidin-biotin interaction, and immobilization of
      antibodies via self-assembled monolayer formation. The fourth strategy is a novel
      method for bacteria enumeration based on the combination of the SPR spectroscopy
      and immunomagnetic separation with using gold-coated magnetic nanoparticles.
      According to results, the most efficient SPR method is the one based on gold
      coated magnetic nanoparticles. This method allows to specifically separate E.
      coli from the environment and to quantify rapidly without any labeling procedure.
      The developed method has a linear range between 30 and 3.0 * 10(4)cfu/ml, and a
      detection limit of 3 cfu/ml. The selectivity of the method was examined with
      Enterobacter aerogenes and Enterobacter dissolvens, which did not produce any
      significant response. The usefulness of the method to detect E. coli in real
      water samples was also investigated, and the results were compared with the
      results from plate-counting method. There was no significant difference between
      the methods (p>0.05).

PMID- 22608767
TI  - Covalent conjugation of avidin with dye-doped silica nanopaticles and preparation
      of high density avidin nanoparticles as photostable bioprobes.
AB  - Progress in biomedical imaging depends on the development of bioprobes with a
      high sensitivity and stability. Fluorescent silica nanoparticles (NPs) covalent
      conjugation of avidin has been proposed for cancer cells imaging by fluorescence
      microscopy. Uniform silica NPs were prepared using water-in-oil (W/O)
      microemulsion methods and primary amine groups were introduced onto the surface
      of the NPs by condensation of tetraethyl orthosilicate (TEOS). Optically stable
      organic dyes, tris(2,2'-bipyridyl) dichlororuthenium(II) hexahydrate (Rubpy),
      were doped inside the silica NPs. The amine functions were transferred to
      carboxyl groups coupled with a linker elongation. Avidin was immobilized at the
      surface of the NPs by covalent binding to the carboxyl linkers. The binding
      capacity of the avidin-covered NPs for ligand biotin was quantified by titration
      with biotin(5-fluorescein) conjugate to 1.25 biotin binding sites/100 nm(2). We
      used biotinylated antibody and cell recognition by fluorescence microscopy
      imaging technique. The lung carcinoma cells were identified easily with high
      efficiency using these antibody-coated NPs. By comparison with fluorescein
      isothiocyanate (FITC), dye-doped silica NPs display dramatically increased
      stability of fluorescence as well as photostability, as compared to the common
      organic dye, when under continuous irradiation.

PMID- 22608768
TI  - Lipopolysaccharides, cytokines, and nitric oxide affect secretion of
      prostaglandins and leukotrienes by bovine mammary gland epithelial cells.
AB  - The aims of this study were to determine the effects of lipopolysaccharides
      (LPS), tumor necrosis factor (TNF), interleukin 1 alpha (IL-1alpha), nitric oxide
      donor (NONOate), or the combination of TNF + IL-1alpha + NONOate on the
      following: (i) secretion of prostaglandin (PG)-F(2alpha), PGE(2), leukotriene
      (LT)-B(4), and LTC(4) by epithelial cells of the teat cavity and lactiferous
      sinus of bovine mammary gland; (ii) messenger RNA (mRNA) transcription of enzymes
      responsible for arachidonic acid (AA) metabolism (prostaglandin-endoperoxide
      synthase 2 [PTGS2], prostaglandin E synthase [PTGES], prostaglandin F synthase
      [PGFS], and arachidonate 5-lipooxygenase [ALOX5]); and (iii) proliferation of the
      cells. The cells were stimulated for 24 h. Prostaglandins and LT were measured by
      enzyme immunoassay, mRNA transcription of enzymes was determined by real-time
      reverse transcription polymerase chain reaction, and the cell viability was
      measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide. All
      factors increased PG secretion, but the highest stimulation was observed after
      TNF and IL-1alpha (P < 0.001). Tumor necrosis factor, NONOate, and TNF + IL
      1alpha + NONOate increased LTB(4) production (P < 0.01), whereas LTC(4) was
      increased by LPS, TNF, and IL-1alpha (P < 0.01). Lipopolysaccharides, TNF, IL
      1alpha, and the reagents combination increased PTGS2, PTGES, and PGFS mRNA
      transcription (P < 0.01), whereas ALOX5 mRNA transcription was increased only by
      TNF (P < 0.001). Lipopolysaccharides, TNF, IL-1alpha, NONOate, and the
      combination of reagents increased the cell number (P < 0.001). Mediators of acute
      clinical Escherichia coli mastitis locally modulate PG and LT secretion by the
      epithelial cells of the teat cavity and lactiferous sinus, which might be a
      useful first line of defense for the bovine mammary gland. Moreover, the
      modulation of PG and LT secretion and the changing ratio of luteotropic (PGE(2),
      LTB(4)) to luteolytic (PGF(2alpha), LTC(4)) metabolites may contribute to
      disorders in reproductive functions.

PMID- 22608769
TI  - Effects of stress on endocrine and metabolic processes and redirection: cross
      talk between subcellular compartments.
AB  - Recent advances in genome analysis and biochemical pathway mapping have advanced
      our understanding of how biological systems have evolved over time. Protein and
      DNA marker comparisons suggest that several of these systems are both ancient in
      origin but highly conserved into today's evolved species. However, remnants of
      some of the more ancient functions of these chemical systems can run in conflict
      with the functions that those same pathways serve in complex organisms and tissue
      systems today. Relevant to the present topic, nitric oxide (NO) and superoxide
      anion (O(2)(*-)), ancient cellular molecules in evolutionary terms, are
      recognized today as both necessary for the well-being and stable health of cells
      but also injurious to cells as elaborated in conjunction with the cellular stress
      response. Why the dichotomy? This question underlies one of the basic issues
      challenging researchers as well as practitioners in their approach to disease
      management. The fundamental proinflammatory response of the innate immune system
      of the host is needed for pathogen control but can be injurious to tissues from
      "collateral damage" from NO- and O(2)(*-)-derived reactive molecules capable of
      affecting protein function via post-translational chemical modification. This
      review highlights newer aspects of the biochemistry of the NO- and O(2)(*-)
      mediated innate proinflammatory response and further show how protein and tissue
      damage via overproduction of reactive nitrogen and oxygen intermediary molecules
      such as peroxynitrite (ONOO(-)) might be targeted to specific epitopes of
      proteins. Changes in the regulation of metabolism in response to proinflammatory
      disease states are discussed for GH signal transduction and tissue specificity.

PMID- 22608770
TI  - The CentriMag ventricular assist device in acute heart failure refractory to
      medical management.
AB  - BACKGROUND: The CentriMag ventricular assist device (VAD) has gained popularity
      in the last several years as rescue support for patients with decompensated heart
      failure. We have used the CentriMag VAD as a bridge to decision device. We
      describe our experience with device placement, use and outcomes. METHODS: This is
      a retrospective study of all patients who underwent CentriMag placement at our
      institution from January 2007 to August 2009. Sixty-three patients had placement
      of a CentriMag device, with 43% (n = 27) of these being placed due to failure of
      medical management. These cases were the focus of our study. RESULTS: Primary
      diagnoses were ischemic cardiomyopathy (n = 17), dilated cardiomyopathy (n = 7)
      or other (n = 3). Mean age was 47.1 (range 7 to 72) years. Prior to implant, 85%
      of patients were on intra-aortic balloon pump (IABP) support, 70% were on
      vasopressors, and 44% were on more than one inotrope. INTERMACS score was 1 in
      67% of patients and 2 in 33% of patients. Six patients were bridged to a long
      term device, 8 to transplantation and 10 to recovery. Eighty-nine percent (24 of
      27) of patients survived to explant and 74% (20 of 27) survived to hospital
      discharge, with a 1-year survival of 68%. Thromboembolic complications occurred
      in 10 patients, including 6 strokes. Compared with patients who survived to
      discharge, those who died had a significantly higher body mass index (30.8 vs
      24.1 kg/m(2), p = 0.003). Survivors to discharge demonstrated significant
      improvements in hepatic and renal function over the course of device support
      while non-survivors did not. CONCLUSIONS: The CentriMag demonstrates promising
      results when used in patients with acute heart failure refractory to medical
      management.

PMID- 22608771
TI  - S262A mutation abolishes protective effects of connexin 43 against hypothermic
      preservation-induced injury in cardiomyocytes.
AB  - BACKGROUND: Alleviation of cold preservation-induced injury is a critical part of
      the heart transplantation process. In this study we investigate the protective
      effect of connexin 43 (Cx43) overexpression against hypothermic preservation
      induced injury in cardiomyocytes. METHODS: Total RNA was prepared from H9c2 cells
      using TRIzol reagent to construct a recombinant vector pEGFP-c1-Cx43, which was
      then transformed into Escherichia coli DH5alpha competent cells. The S262A Cx43
      containing a mutant site was obtained by RT-PCR. The protein expression of total
      Cx43 and p-S262 Cx43 were assessed by Western blot. Cell viability and LDH
      release in the culture medium was measured. RESULTS: Restrictive enzyme reaction
      assay and DNA sequencing confirmed that the recombinant vector pEGFP-c1-Cx43 and
      pEGFP-c1-S262A-Cx43 were constructed correctly. After H9c2 cells were
      hypothermically preserved in Celsior solution for 12 to 48 hours, the cell
      viability decreased and LDH release increased. Compared with empty vector cells,
      overexpression of Cx43 prevented the hypothermic preservation-induced decrease in
      cell viability and increase in LDH release, which was independent of the absence
      of gap junctions. S262A mutation prevented S262 phosphorylation of Cx43 and also
      abolished protection of Cx43 overexpression against cold preservation-induced
      cardiomyocyte injury. CONCLUSIONS: In H9c2 cells hypothermically preserved for up
      to 48 hours, overexpression of Cx43 could protect against cold preservation
      induced injury. Phosphorylation of Cx43 at S262 may play an essential role in the
      preservation of donor hearts.

PMID- 22608773
TI  - Intrinsic motivation and metacognition as predictors of learning potential in
      patients with remitted schizophrenia.
AB  - BACKGROUND: Previous research has suggested that neurocognitive functioning
      predicts best the potential of patients with schizophrenia to acquire newly
      learned material, which, in turn may impact patients' social functioning. Recent
      studies have also shown that intrinsic motivation and metacognitive abilities
      play a decisive role in social functioning in schizophrenia. Accordingly, the
      present study sought to examine the relationship between intelligence,
      motivation, metacognition, and learning during a cognitive remediation
      experimental training. We hypothesized that metacognition and intrinsic
      motivation would have a strong relationship and independently predict learning
      potential. METHOD: Thirty-two patients with schizophrenia who fulfilled the
      criteria of functional remission were recruited. In a pre-training-post
      experimental design, patients' learning potential was assessed using previously
      defined cognitive remediation training for WCST. Intrinsic motivation was
      examined using Intrinsic Motivation Inventory for schizophrenia; mastery, a
      domain of metacognition, was measured using the Metacognitive Assessment Scale.
      RESULTS: Metacognition significantly correlated with subdomains of intrinsic
      motivation. Patients with higher intrinsic motivation and preserved metacognition
      improved more in the learning paradigm compared to poorly motivated patients and
      patients with reduced metacognitive abilities. In particular, "mastery" was
      determined as an independent predictor of learning potential. CONCLUSIONS:
      Motivation and metacognition are important predictors of learning in
      schizophrenia. Psychological interventions in schizophrenia may therefore
      consider incorporating techniques to stimulate metacognitive and motivational
      abilities as well as developing individualized training programs.

PMID- 22608772
TI  - Higher prevalence of sexual dysfunction in colon and rectal cancer survivors
      compared with the normative population: a population-based study.
AB  - BACKGROUND: To compare colorectal cancer survivors with a normative population
      regarding erectile dysfunction, ejaculation problems, dyspareunia, dry vagina,
      sexual functioning (SF) and enjoyment (SE). In addition, the sociodemographic,
      clinical and psychological correlates of (dys)function in survivors are examined.
      PATIENTS AND METHODS: The European Organisation for Research and Treatment of
      Cancer (EORTC) QLQ-CR38 sexuality subscales were completed by survivors (n=1371;
      response rate 82%), of which 1359 received surgical treatment and were included
      in the analysis. The normative population consisted of 400 participants (response
      rate 78%). RESULTS: Erectile problems were more often present in rectal cancer
      (54%) than colon cancer survivors (25%) and the normative population (27%;
      p<.0001). They also had more ejaculation problems (68%) than colon cancer
      survivors (47%; p<.001). Dry vagina was common in colon (28%) and rectal cancer
      survivors (35%), while the normative population scored lower (5%; p=.003). In
      addition, colon (9%) and rectal cancer survivors (30%) experienced more pain
      during intercourse than the normative population (0%; p=.001). SE for men was
      similar across groups, while women with colorectal cancer reported lower scores
      than the normative population. Higher age, being a woman, not having a partner, a
      low educational level, rectal cancer, depressive symptoms and fatigue were
      associated with lower SF. Lower SE was associated with higher age and being a
      woman, depressive symptoms and cardiovascular disease. CONCLUSION: SF was
      deteriorated in both sexes after cancer, which affected women's SE negatively.
      Attention towards sexual (dys)function in colorectal cancer survivors is needed.

PMID- 22608774
TI  - The relationship between psychiatric symptoms and glycemic status in a Chinese
      population.
AB  - With the exception of depression and anxiety, there has been no study designed to
      evaluate the association between other psychiatric symptoms and Type 2 diabetes.
      The aim of this study was to investigate the relationship between different
      psychiatric symptoms and diabetes as well as pre-diabetes (Pre-DM) in a Chinese
      population. Totally, 9561 participants without a history of diabetes, depression,
      psychosis, use of hypnotics, and abnormal thyroid function were enrolled.
      Psychiatric symptoms were measured by Brief Symptoms Rating Scale questionnaire,
      which consists of three global indices [General Severity Index (GSI), Total
      Number of Positive Symptoms (PST), and Positive Symptom Distress Index (PSDI)]
      and ten subscales, including somatization, obsession, interpersonal sensitivity,
      depression, anxiety, hostility, phobia, paranoid ideation, psychoticism and
      additional symptoms. Different glycemic statuses included normal glucose
      tolerance (NGT), Pre-DM, and newly-diagnosed diabetes (NDD) group. GSI,
      somatization, hostility, phobia, psychoticism, and additional symptoms were the
      factors positively associated with NDD as well as pre-DM in an age-adjusted
      model. After adjustments for age, gender, body mass index, educational level,
      hypertension, plasma triglycerides and creatinine, smoking, alcohol use, regular
      exercise, marital status, and family history of diabetes mellitus, the following
      psychiatric symptoms were independently related to both NDD and pre-DM: GSI, PST,
      somatization, obsession, interpersonal sensitivity, depression, anxiety,
      hostility, phobia, psychoticism, and additional symptoms. In addition to
      depression and anxiety, global indices of psychiatric symptoms and other
      subscales, including somatization, obsession, interpersonal sensitivity,
      hostility, phobia, psychoticism and additional symptoms, may have an impact on
      both diabetes and Pre-DM.

PMID- 22608775
TI  - Optimisation of a sensitive method based on ultrasound-assisted emulsification
      microextraction for the simultaneous determination of haloanisoles and volatile
      phenols in wine.
AB  - In this study, an ultrasound-assisted emulsification-microextraction (USAEME) has
      been optimised for the sensitive determination of haloanisoles (2,4,6
      trichloroanisole (TCA), 2,3,4,6-tetrachloroanisole (TeCA), 2,4,6-tribromoanisole
      (TBA) and pentachloroanisole (PCA)) and volatile phenols (4-ethylphenol (4-EP), 4
      ethylguaiacol (4-EG), 4-vinylphenol (4-VP) and 4-vinylguaiacol (4-VG)) in wine
      using gas chromatography coupled to tandem mass spectrometry (GC-MS/MS).
      Optimisation of USAEME method was performed by evaluating the different
      parameters that influence the recovery of the analytes in the extract. Firstly,
      extraction solvent was selected. Subsequently its volume, the ionic strength and
      the time and temperature at which the extraction must be performed were
      simultaneously evaluated by means of experimental design methodology. After
      optimisation step, the analytical characteristics of the method were evaluated.
      Satisfactory linearity (with correlation coefficients over 0.989), repeatability
      (below 11.5%) and inter-day precision (below 11.7%) were obtained for all target
      analytes. For all the studied compounds, detection limits obtained were similar
      or even lower than previously reported. In addition, the developed method was
      successfully applied to the analysis of wine samples. To the best of our
      knowledge, this is the first time that USAEME has been applied to simultaneously
      determine the compounds responsible for cork taint and Brett character in wine.

PMID- 22608776
TI  - Qualitative analysis of algal secretions with multiple mass spectrometric
      platforms.
AB  - Lipid secretions from algae pose a great opportunity for engineering biofueler
      feedstocks. The lipid exudates could be interesting from a process engineering
      perspective because lipids could be collected directly from the medium without
      harvesting and disrupting cells. We here report on the extracellular secretions
      of algal metabolites from the strain UTEX 2341 (Chlorella minutissima) into the
      culture medium. No detailed analysis of these lipid secretions has been performed
      to date. Using multiple mass spectrometric platforms, we observed around 1000
      compounds and were able to annotate 50 lipids by means of liquid chromatography
      coupled to accurate mass quadrupole time-of-flight mass spectrometry (LC-QTOF),
      direct infusion with positive and negative electrospray ion trap mass
      spectrometry and gas chromatography coupled to mass spectrometry (GC-MS). These
      compounds were annotated by tandem mass spectral (MS/MS) database matching and
      retention time range filtering. We observed a series of triacylglycerols (TG),
      sulfoquinovosyldiacylglycerols (SQDG), phosphatidylinositols and
      phosphatidylglycerols, as well as betaine lipids diacylglyceryl-N,N,N
      trimethylhomoserines (DGTS).

PMID- 22608777
TI  - Supercritical fluid extraction of free amino acids from broccoli leaves.
AB  - The extraction of free amino acids (AAs) from broccoli leaves using supercritical
      fluid extraction (SFE) with CO(2) modified with methanol, is presented in this
      work. The effect of the different variables was studied, showing the percentage
      of methanol a strong influence on the extraction. The best results in terms of
      extraction yield were obtained at 250 bar, 70 degrees C, 35% methanol as organic
      modifier, a flow rate of 2 mL/min, and 5 min and 30 min as static and dynamic
      extraction times, respectively. The extraction yield obtained with the SFE method
      was comparable to that obtained employing conventional solvent extraction with
      methanol-water (70:30) and minor than using water, but the relative proportion of
      the AAs in the extracts was very different. For example, the use of SFE allowed
      the enrichment in proline and glutamine of the extracts. The selected conditions
      were applied to obtain SFE extracts of broccoli leaves from different varieties
      (Naxos, Nubia, Marathon, Parthenon and Viola). The highest levels of AAs were
      found in the SFE extracts from the Nubia variety.

PMID- 22608778
TI  - Application of gas chromatography time-of-flight mass spectrometry for target and
      non-target analysis of pesticide residues in fruits and vegetables.
AB  - In this work, the capability of gas chromatography coupled to time-of-flight mass
      spectrometry (GC-TOF MS) for quantitative analysis of pesticide residues has been
      evaluated. A multiclass method for rapid screening of pesticides (insecticides,
      acaricides, herbicides and fungicides) in fruit and vegetable matrices has been
      developed and validated, including detection, identification and quantification
      of the analytes. To this aim, several food matrices were selected: high water
      content (apples, tomatoes and carrots), high acid content (oranges) and high oil
      content (olives) samples. The well known QuEChERS procedure was applied for
      extraction of pesticides, and matrix-matched calibration using relative responses
      versus internal standard was used for quantification. The sample extracts were
      analyzed by GC-TOF MS. Up to five ions using narrow window (0.02 Da)-extracted
      ion chromatograms at the expected retention time were monitored using a target
      processing method. The most abundant ion was used for quantification while the
      remaining ones were used for confirmation of the analyte identity. Method
      validation was carried out for 55 analytes in the five sample matrices tested at
      three concentrations (0.01, 0.05 and 0.5 mg/kg). Most recoveries were between 70%
      and 120% with relative standard deviations (RSDs) lower than 20% at 0.05 and
      0.5mg/kg. At 0.01 mg/kg, roughly half of the pesticides could be satisfactorily
      validated due to sensitivity limitations of GC-TOF MS, which probably affected
      the ion ratios used for confirmation of identity. In the case of olive samples,
      results were not satisfactory due to the high complexity of the matrix. An
      advantage of TOF MS is the possibility to perform a non-target investigation in
      the samples by application of a deconvolution software, without any additional
      injection being required. Accurate-mass full-spectrum acquisition in TOF MS
      provides useful information for analytes identification, and has made feasible in
      this work the discovery of non-target imazalil, fluoranthene and pyrene in some
      of the samples analyzed.

PMID- 22608779
TI  - Second-line therapy after VEGF targeted therapy in metastatic renal cancer: a law
      of diminishing returns.

PMID- 22608780
TI  - Efficacy of GLP-1 receptor agonists and DPP-4 inhibitors: meta-analysis and
      systematic review.
AB  - BACKGROUND: Considerable clinical data on the treatment of type 2 diabetes with
      incretin-based therapies (glucagon-like peptide 1 receptor agonists [GLP-1RAs]
      and dipeptidyl-peptidase IV [DPP-4] inhibitors) are available. OBJECTIVE: This
      meta-analysis was performed to support the understanding of the overall evidence
      by summarizing the findings from studies of the incretin-based therapies.
      METHODS: The MEDLINE, EMBASE, BIOSIS, and BIOSIS trial databases were searched
      for relevant literature published between January 1, 1990, and June 30, 2011.
      Search terms included GLP-1, DPP-4, the names of drugs that have been approved by
      the US Food and Drug Administration for the treatment of diabetes, and the names
      of drugs that have not been approved but are in late-stage research. Studies were
      included if they were randomized controlled trials of 12 to 52 weeks' duration
      and having change from baseline in hemoglobin (Hb) A(1c) as the primary end
      point. The random effects meta-analyses models examined HbA(1c), fasting plasma
      glucose (FPG), and body weight for individual therapies, but did not compare
      effects between therapies. RESULTS: The reviewers identified 362 unique clinical
      studies, of which 80 were eligible for inclusion in the present meta-analysis.
      Mean baseline HbA(1c) values ranged from 7.4% to 10.3% (GLP-1RA studies) and 7.2%
      to 9.3% (DPP-4 inhibitor studies). The highest maintenance doses of the GLP-1RAs
      and the DPP-4 inhibitors were associated with changes from baseline in mean
      HbA(1c) of -1.1% to -1.6% and -0.6% to -1.1%, respectively. Mean reductions in
      FPG with exenatide once weekly (QW) or liraglutide once daily were apparently
      greater than those with exenatide twice daily (BID) and the DPP-4 inhibitors,
      with the exception of vildagliptin. Mean weight losses with the GLP-1RAs and the
      DPP-4 inhibitors were >-2.0 and -0.2 to -0.6 kg, respectively. The limitations of
      the present analysis included a lack of adjustment for placebo use and interstudy
      heterogeneity associated with differences in methodology (eg, management of
      concurrent medications, blinding, criteria for treatment discontinuation).
      CONCLUSIONS: All of the incretin-based therapies in the present meta-analysis
      were associated with significant reductions from baseline in HbA(1c) and FPG.
      Further direct comparative studies between the GLP-1RAs and the DPP-4 inhibitors
      and within the GLP-1RA class are justified.

PMID- 22608781
TI  - Functional independence between numerical and visual space: evidence from right
      brain-damaged patients.
AB  - What is the relationship between numerical and visual space? Here we tried to
      shed new light on this debated issue investigating whether and how the two forms
      of representation are associated or dissociated when co-activated. We carried out
      a series of visual-numerical bisection experiments on a large group of right
      brain-damaged patients (N=32) with and without left neglect. We examined (a) the
      degree of association between the pathological rightward error in the bisection
      of numerical intervals and left neglect (experiment 1); (b) if the size of the
      numerical interval modulates spatial errors in bisection tasks in which numerical
      and visual space representations are co-activated (experiment 2). The results
      showed that (a) numerical bisection error and left spatial neglect are doubly
      dissociated and that, when both are present, they are not correlated; (b) the
      size of the numerical interval did not affect the spatial bisection error but
      influenced the numerical bisection error. These data suggest that attentional
      processes involved in the navigation along visual space and numerical internal
      representations are independent neurocognitive operations. We must emphasize that
      our findings should be taken with caution because they are based mainly on
      negative results.

PMID- 22608782
TI  - Predictive value of loci in VEGF pathway genes in bevacizumab treatment.

PMID- 22608783
TI  - VEGF pathway genetic variants as biomarkers of treatment outcome with
      bevacizumab: an analysis of data from the AViTA and AVOREN randomised trials.
AB  - BACKGROUND: No biomarkers that could guide patient selection for treatment with
      the anti-VEGF monoclonal antibody bevacizumab have been identified. We assessed
      whether genetic variants in the VEGF pathway could act as biomarkers for
      bevacizumab treatment outcome. METHODS: We investigated DNA from white patients
      from two phase 3 randomised studies. In AViTA, patients with metastatic
      pancreatic adenocarcinoma were randomly assigned to receive gemcitabine and
      erlotinib plus either bevacizumab or placebo. In AVOREN, patients with metastatic
      renal-cell carcinoma were randomly assigned to receive interferon alfa-2a plus
      either bevacizumab or placebo. We assessed the correlation of 138 SNPs in the
      VEGF pathway with progression-free survival and overall survival in a
      subpopulation of patients from AViTA. Significant findings were confirmed in a
      subpopulation of patients from AVOREN and functionally studied at the molecular
      level. FINDINGS: We investigated DNA of 154 patients from AViTA, of whom 77
      received bevacizumab, and 110 patients from AVOREN, of whom 59 received
      bevacizumab. Only rs9582036, a SNP in VEGF receptor 1 (VEGFR1 or FLT1), was
      significantly associated with overall survival in the bevacizumab group of AViTA
      after correction for multiplicity (per-allele hazard ratio [HR] 2.1, 95% CI 1.45
      3.06, p=0.00014). This SNP was also associated with progression-free survival
      (per-allele HR 1.89, 1.31-2.71, p=0.00081) in bevacizumab-treated patients from
      AViTA. AC and CC carriers of this SNP exhibited HRs for overall survival of 2.0
      (1.19-3.36; p=0.0091) and 4.72 (2.08-10.68; p=0.0002) relative to AA carriers. No
      effects were seen in placebo-treated patients and a significant genotype by
      treatment interaction (p=0.041) was recorded, indicating that the VEGFR1 locus
      containing this SNP serves as a predictive marker for bevacizumab treatment
      outcome in AViTA. Fine-mapping experiments of this locus identified rs7993418, a
      synonymous SNP affecting tyrosine 1213 in the VEGFR1 tyrosine-kinase domain, as
      the functional variant underlying the association. This SNP causes a shift in
      codon usage, leading to increased VEGFR1 expression and downstream VEGFR1
      signalling. This VEGFR1 locus correlated significantly with progression-free
      survival (HR 1.81, 1.08-3.05; p=0.033) but not overall survival (HR 0.91, 0.45
      1.82, p=0.78) in the bevacizumab group in AVOREN. INTERPRETATION: A locus in
      VEGFR1 correlates with increased VEGFR1 expression and poor outcome of
      bevacizumab treatment. Prospective assessment is underway to validate the
      predictive value of this novel biomarker. FUNDING: F Hoffmann-La Roche.

PMID- 22608784
TI  - [Alcohol consumption in adolescents (12 to 17 years): the point of view of health
      professionals].
AB  - OBJECTIVE: To find out the opinions of health professionals on adolescent alcohol
      drinking and their evaluation of the existing legal regulation measures.
      METHODOLOGY:  DESIGN: Qualitative and exploratory study, based on semi-structured
      interviews. SETTING: Four cities representing four different regions in Spain:
      Palma de Mallorca, Granada, Barcelona and Pamplona. PARTICIPANTS: A total of 36
      physicians and nurses from four Spanish regions, working in Primary Care and
      Emergency Care, selected by intentiones samples. MEASUREMENTS: A total of 36 deep
      interviews, analysed using the software Nudist Vivo 4.0. RESULTS: Health
      professionals accept their important role in preventing and intervening in
      adolescent alcohol drinking. Generally, they consider it as a public health
      problem. Prevention is associated with Primary Care, while the Emergency
      Departments act in specific situations of alohol abuse. Adolescents infrequently
      visit Primary Care, thus prevention must centre on education system and constant
      coordination between health professional and parents. Health personnel do not
      have sufficient knowledge on legal regulations. They consider educational
      measures as more efficient than sanctions. CONCLUSIONS: Specific professional
      training is required in order to guarantee the coordination between the health
      and education systems and the family.

PMID- 22608785
TI  - [Influenza vaccination cover by health care levels in a health department:
      periods 2006-2007 to 2010-2011].

PMID- 22608786
TI  - Was it the zebu?

PMID- 22608787
TI  - Nude photography: abuse, obsession, delusion, and finally depression.

PMID- 22608788
TI  - Intravenous immunoglobulin (IVIg) for refractory and difficult-to-treat
      infections.
AB  - Traditionally, intravenous immunoglobulin (IVIg) has been used as replacement
      therapy for patients with primary or secondary immunoglobulin deficiencies.
      Increasingly, IVIg is being used (in doses higher than for replacement therapy)
      in certain bacterial or viral infectious diseases. A variety of modes of action
      have been attributed to the beneficial effects of IVIg, including its interaction
      with T-cell function, antigen-presenting cell maturation/presentation, combined
      with a general "tune down" effect on inflammatory reactions. More often, IVIg is
      being evaluated in clinical trials for the treatment of refractory and difficult
      to-treat chronic infections. The evidence, molecular mechanisms, and rationale
      for the use of adjunct IVIg therapy in infectious diseases are reviewed, and its
      potential use in the adjunct treatment of difficult-to-treat drug-resistant
      tuberculosis discussed.

PMID- 22608789
TI  - Recent progress in the treatment of proliferative lupus nephritis.
AB  - The recent decades have witnessed significant progress in the treatment of lupus
      nephritis. Existing immunosuppressive regimens have been refined to enhance
      efficacy and reduce adverse effects, resulting in improvements in renal and
      patient survival and patients' quality of life. This review focuses on the new
      treatments that have emerged over the past 2 decades. The data and methodology of
      important clinical trials are discussed to highlight the important findings and
      their limitations. The role of mycophenolate mofetil as induction or maintenance
      immunosuppressive treatment is discussed in detail. Racial variations in
      prognosis and treatment response are evident. With increasing treatment options
      and better appreciation of patient characteristics that impact on response and
      tolerance, the management of lupus nephritis has become more individualized. The
      choice and the dosing regimen of immunosuppressive agents should take into
      account factors such as race, type of lupus nephritis, disease severity, renal
      reserve, and prior disease course, to aim for an optimal balance of benefit and
      risk.

PMID- 22608790
TI  - Mortality and coronary heart disease in euthyroid patients.
AB  - BACKGROUND: Subclinical thyroid dysfunction is associated with increased
      mortality and cardiovascular risk. It is unknown whether this association remains
      within normal thyroid function range. METHODS: The study was conducted using the
      computerized database of the Sharon-Shomron district of Clalit Health services.
      Included were subjects aged >=40 years with normal thyroid function. Patients
      with a history of thyroid or cardiovascular diseases or diabetes were excluded.
      The primary end points were all-cause mortality and the need for coronary
      revascularization with either percutaneous coronary intervention or coronary
      artery bypass grafting. RESULTS: The 42,149 participants were stratified into 3
      groups of equal thyrotropin intervals (0.35-1.6, 1.7-2.9, and 3-4.2 mIU/L).
      During a mean follow-up of 4.5+/-2.1 years, 4239 (10.1%) participants died and
      1575 (3.7%) underwent coronary revascularization. For both women and men, the
      lowest mortality rates were observed in the intermediate thyrotropin group.
      Nevertheless, only for the low thyrotropin group, mortality risk remained
      significantly higher as compared with the intermediate thyrotropin group, even
      following multivariate model adjusted for the conventional cardiovascular risk
      factors, in both women (odds ratio 1.22; 95% confidence interval, 1.09-1.36 for
      the low thyrotropin group, compared with the intermediate group) and men (odds
      ratio 1.14; 95% confidence interval, 1.01-1.3 for the low thyrotropin group,
      compared with the intermediate group). There was no significant difference in the
      need for coronary revascularization among the 3 thyrotropin groups in both men
      and women. CONCLUSIONS: Low thyrotropin level within the reference range is
      associated with increased risk for all-cause mortality.

PMID- 22608791
TI  - Outcome of endovascular treatment of traumatic aortic transection.
AB  - OBJECTIVE: The purpose of this study was to analyze our experience of thoracic
      endovascular aortic repair (TEVAR) in patients with traumatic aortic transection.
      METHODS: This was a single-center consecutive case series that was conducted at
      the Uppsala University Hospital, Tertiary Referral Center. There were a total of
      17 consecutive patients undergoing TEVAR for traumatic thoracic aortic
      transection. All patients undergoing TEVAR for aortic transection were registered
      prospectively and their medical records were reviewed regarding technical
      details, mechanism of injury, and concomitant injuries. Long-term outcome was
      analyzed with respect to need for reintervention and survival. RESULTS: Between
      2001 and 2010, 17 patients underwent TEVAR for traumatic aortic injury. Median
      age was 42 years (range, 18-77 years), and 15 of 17 patients (88%) were men.
      Fourteen patients had been involved in motor vehicle accidents, two had fallen
      from heights, and one fell off a bicycle on a slope. In all cases, the aortic
      injury was located in the proximity of the origin of the left subclavian artery.
      All patients had concomitant injuries. In all patients, a single stent graft was
      sufficient to exclude the injured part of the aorta. The median cover length was
      120 mm (range, 100-200 mm). In-hospital mortality was 24% (4 of 17 patients). One
      patient died perioperatively and three postoperatively, two from brain injuries
      and one from multiorgan failure. After a median follow-up of 36 months (range, 10
      98 months), three patients underwent reintervention (18%), each patient only
      once; one for a type I endoleak, and two for pseudocoarctation secondary to stent
      graft infolding. Two were treated endovascularly, and one had a stent graft
      explantation. CONCLUSIONS: Endovascular repair allows rapid and minimally
      invasive therapy in patients with traumatic aortic injury with good technical
      results. The outcome is highly dependent on the severity of other concurrent
      injuries.

PMID- 22608792
TI  - Treatment of primary infected aortic aneurysm without aortic resection.
AB  - BACKGROUND: We sought to determine the safety and efficacy of two different
      treatment strategies for patients with primary infected aortic aneurysms,
      including antibiotic treatment alone and endovascular aneurysm repair (EVAR) with
      aggressive antibiotic treatment, as alternatives to the established treatment of
      open surgical repair. METHODS: We conducted a retrospective chart review of
      patients who were treated for infected aortic aneurysm without undergoing aortic
      resection from January 2000 to December 2010 at a single institution. RESULTS: A
      total of 40 patients underwent traditional open repair during the study period.
      Sixteen patients with infected aortic aneurysm (11 men; median age, 70; range, 44
      80 years) were identified as not having undergone aortic resection during the 11
      years reviewed in the study. Nine patients received antibiotic treatment only
      (group I) and seven patients underwent EVAR with aggressive antibiotic treatment
      (group II). Salmonella species were isolated from seven patients in group I, and
      oxacillin-resistant Staphylococcus aureus was isolated from the remaining two
      patients. In group II, six patients had blood culture results showing Salmonella
      species and one patient had a blood culture result showing Escherichia coli.
      Group I (7 of 9 patients; 78%) had a higher hospital mortality rate than group II
      (0%; P = .003). Mean follow-up among survivors was 10 +/- 15 months (range, 1-37
      months). One patient in group II developed a reinfection episode (14%). There was
      no significant difference between group I (67%; SE, 27.2%) and group II (86%; SE,
      13.2%) in the 3-month survival rates (log-rank, P = .39). CONCLUSIONS: Our
      results support the premise that EVAR is beneficial for the patients with
      infected aortic aneurysm. Treating an infected aortic aneurysm with antibiotics
      alone could not stop aneurysm expansion and eradicate the aortic infection before
      the aneurysm ruptures. For the patients with infected aortic aneurysms who have
      limited life expectancy and multiple comorbidities, EVAR with aggressive
      antibiotic treatment should be considered preferentially over antibiotic
      treatment alone.

PMID- 22608793
TI  - Treatment and medical follow-up of a boy with urethral triplication.
AB  - A 17-month-old boy presented with a mild abnormal appearance of the foreskin and
      was enrolled into our department. The boy had one normal urethra, one accessory
      urethra originating from the bladder neck and opening into dorsal pennies, and
      one accessory urethra opening into glans penis but not communicating with the
      other two urethras. At surgery, the midshaft epispadias was excised and two
      meatal openings remained untouched. Two weeks after operation, a repeat voiding
      cystourethrogram showed no signs of abnormality. During the past 4-year follow
      up, the patient reported good urethral voiding, with no complications such as
      urodynia or urinary tract infection.

PMID- 22608794
TI  - Editorial comment.

PMID- 22608795
TI  - Editorial comment.

PMID- 22608796
TI  - Novel androgen receptor gene mutation in patient with complete androgen
      insensitivity syndrome.
AB  - To present a rare case of a patient probably with complete androgen insensitivity
      syndrome (CAIS) and studied its potential genetic cause. A 24-year-old woman with
      a normal-appearing vulva and vagina presented to us because of primary
      amenorrhea. Imaging studies showed no uterus or ovary development but inguinal
      cryptorchism. Histopathologic examination revealed normal testicular structures.
      Sequencing the CAIS-associated androgen receptor gene revealed a novel missense
      mutation of T to G (F698L). A novel androgen receptor gene mutation in the ligand
      binding domain was detected in the present patient with CAIS, supporting the
      important role of an androgen receptor defect in the etiology of CAIS.

PMID- 22608797
TI  - Greater percent-free testosterone is associated with high-grade prostate cancer
      in men undergoing prostate biopsy.
AB  - OBJECTIVE: To analyze the serum androgen concentrations in men who underwent an
      initial prostate biopsy, focusing on the percent-free testosterone (%FT) as a
      predictor of low- and high-grade prostate cancer (PCa). Most studies have
      suggested that the absolute serum testosterone and free testosterone levels are
      not related to PCa risk. However, to date, the concurrent effect of free and
      total testosterone levels has not been evaluated. In particular, the association
      of the %FT (free testosterone/total testosterone) with PCa risk has not been
      explored. METHODS: From 2006 to 2010, we collected data on 812 white Italian men
      with no history of PCa who underwent 12-core biopsy. The testosterone, free
      testosterone, and %FT (free testosterone/total testosterone) were examined as
      predictors of low-grade (Gleason score of <= 6) and high-grade (Gleason score >=
      7) PCa using crude and adjusted multinomial logistic regression analysis.
      RESULTS: On multivariate analysis, testosterone (P >= .11) and free testosterone
      (P >= .45) were not significantly associated with low- or high-grade PCa. A
      greater %FT level significantly predicted high-grade PCa on both crude (P = .01)
      and multivariate (P = .02) analysis but not low-grade PCa (P >= .38). When
      examined in tertiles, men in the greatest %FT tertile had a significant twofold
      increased risk of high-grade PCa (odds ratio 2.04, 95% confidence interval 1.23
      3.37, P = .005). CONCLUSION: In white Italian men, a greater %FT level was
      associated with an increased risk of high-grade PCa on initial prostate biopsy.
      These findings suggest that a high %FT level, rather than the absolute androgen
      levels, might be associated with high-grade PCa. Additional studies are needed to
      confirm our findings.

PMID- 22608798
TI  - Psychometric characteristics of a condition-specific, health-related quality-of
      life survey: the FACT-Vanderbilt Cystectomy Index.
AB  - OBJECTIVE: Radical cystectomy (RC) for bladder cancer can be associated with
      significant morbidity and alterations in health-related quality of life (HRQOL).
      The Functional Assessment of Cancer Therapy--Vanderbilt Cystectomy Index (FACT
      VCI) is a condition-specific HRQOL survey for patients undergoing RC and urinary
      diversion (UD) for bladder cancer. This study evaluates the reliability,
      validity, and responsiveness of the Vanderbilt cystectomy index (VCI). METHODS:
      The FACT-VCI was administered to patients with bladder cancer undergoing RC and
      UD (n = 190) at 2 major cancer centers. Statistical methods included principal
      components analysis, Cronbach's coefficient alpha, and nonparametric correlation
      coefficients. The Functional Assessment of Cancer Therapy--General (FACT-G) was
      used to test criterion-related validity and a linear mixed model tested the
      effects of time and diversion type on longitudinal VCI scores. RESULTS: A single
      summary score of 15 gender-neutral items (VCI-15) represented the optimum
      solution for postoperative data, which was internally consistent (alpha = 0.85),
      had strong retest reliability (rho = 0.891), and was associated with all FACT-G
      scales and total score (rho >= 0.38, P <.001). Preoperatively, the VCI-15 was
      internally consistent (alpha = 0.77) and was associated with the FACT-G physical
      and functional scales and total score (rho >= 0.41, P <.001). Although VCI-15
      scores at postoperative year 1 did not differ from preoperative values overall (P
      = .145), they did differ by diversion type (P = .027), with no substantive change
      after orthotopic neobladder (40 +/- 9 vs 39 +/- 10) but with a clinically
      significant improvement after an ileal conduit (39 +/- 11 vs 44 +/- 11).
      CONCLUSION: The VCI-15 is a reliable and valid condition-specific HRQOL survey
      for patients with bladder cancer undergoing RC and UD. Future studies of RC
      patients should measure HRQOL using validated, condition-specific forms, such as
      the FACT-VCI.

PMID- 22608799
TI  - Evaluative care guideline compliance is associated with provision of benign
      prostatic hyperplasia surgery.
AB  - OBJECTIVE: To determine the impact of evaluative care guideline compliance on
      surgical intervention for benign prostatic hyperplasia (BPH). METHODS: From
      Medicare claims data, we developed a cohort of men new to a urologist with a
      diagnosis of BPH. We determined urologists' compliance with guideline recommended
      care (3 months) and their time- and geography-standardized average monthly
      Medicare expenditures (1 year). At the level of the urologist, we assessed the
      impact of these measures on the use of surgical therapy within 1 year of the new
      patient visit. RESULTS: Of 10 248 patients in the cohort, 675 received surgical
      intervention (6.7%). Guideline compliance (2% received surgery in highest
      quintile; 11% lowest quintile) was associated with surgical intervention. The
      results were robust to adjustment for patient and surgeon factors (Guideline
      Compliance, odds ratio = 0.09; 95% confidence interval = 0.06-0.15, highest to
      lowest adherence). CONCLUSION: Urologists who tend to follow the AUA best
      practice guidelines for BPH evaluation perform surgical interventions on their
      BPH patients less frequently than urologists who do not follow these guidelines.

PMID- 22608800
TI  - Safety and efficacy of a novel ureteral occlusion device.
AB  - OBJECTIVE: To evaluate the safety of a novel ureteral occlusion device and
      compare its performance with that of other devices and guidewires. METHODS: The
      XenX (Xenolith Medical) was tested in an ex vivo porcine model to determine the
      percentage of denuded urothelium because of manipulation within the ureter, the
      capacity to prevent stone migration during laser lithotripsy, stent
      compatibility, and the ability to be used for stent placement. Comparative
      evaluations of the insertion forces and maneuverability were conducted in an in
      vitro ureter model with the XenX, Stone Cone (Boston Scientific), NTrap (Cook
      Urological), HiWire (Cook Urological), Roadrunner (Cook Urological), and Sensor
      (Boston Scientific). Stone migration efficacy was measured using a controlled
      distribution of stones in 4- and 10-mm silicone tubing with the XenX, NTrap, and
      Stone Cone. RESULTS: The XenX was safely manipulated within the ureter, prevented
      significant particle migration during laser lithotripsy, and effectively placed
      stents. The NTrap required the greatest force when attempting to navigate past a
      stone (P = .0003), followed by the Stone Cone (P = .009), with little difference
      among the other devices (P > .72). No differences were found for the passing
      forces (P = .061), interval to pass (P = .30), or number of attempts to pass the
      stone (P = .68). The XenX prevented stone migration the most, with more notable
      differences in the 10- than in the 4-mm tubing. CONCLUSION: Ex vivo evaluations
      hold promise for the XenX to be safely and effectively used during ureteroscopic
      procedures. Clinical evaluations are warranted to confirm the safety and
      performance of the XenX relative to the other ureteral occlusion devices.

PMID- 22608801
TI  - Relationship between glomerular filtration rate and 24-hour urine composition in
      patients with nephrolithiasis.
AB  - OBJECTIVE: To examine the relationship between GFR and 24-hour urine composition
      in patients with nephrolithiasis to understand how renal function may affect
      stone risk. Alterations in glomerular filtration rate (GFR) are associated with a
      number of physiological changes. METHODS: A retrospective, institutional review
      board-approved review of patients from 2 metabolic stone clinics was performed.
      One-way analysis of variance and multivariate linear regression models were used
      to evaluate the relationship between GFR quintile and 24-hour urine composition.
      RESULTS: A total of 403 patients (241 male, 162 female) with a mean age of 52.6
      +/- 14.2 years were included in the study. On univariate analysis, decreasing GFR
      by quintile was associated with significant reductions in urine calcium, citrate,
      supersaturation of calcium oxalate, and supersaturation of calcium phosphate (P <
      .05 for each). In multivariate linear regression models, decreasing GFR by
      quintile was associated with significant decreases in urine calcium (beta = 
      11.2, 95% CI = -18.3 to 4.01), urine citrate (beta = -32.4, 95% CI = -54.1 to
      10.8), oxalate (beta = -1.83, 95% CI = -2.85 to 0.81), supersaturation of calcium
      oxalate (beta = -0.58, 95% CI = 0.84 to 0.33) and supersaturation of calcium
      phosphate (beta = -0.09, 95% CI = 0.17 to 0.02), as well as an increase in urine
      magnesium (beta = 3.40, 95% CI = 0.7 to 6.1). CONCLUSION: Reduction in GFR is
      associated with decreased urine calcium, oxalate, and citrate, and increased
      urine magnesium. These findings have implications for treatment of patients with
      stone disease and impaired renal function.

PMID- 22608802
TI  - Effect of socioeconomic status on 24-hour urine composition in patients with
      nephrolithiasis.
AB  - OBJECTIVE: To examine the relationship between the poverty and education levels
      and 24-hour urine composition in patients with nephrolithiasis because little is
      known about the relationship between socioeconomic status and kidney stone risk.
      METHODS: A retrospective review was performed of patients evaluated at 2
      metabolic stone clinics. The poverty level (ie, percentage of those living below
      the poverty level) and education level (ie, percentage of those with a high
      school education or greater) for each postal code were determined from the U.S.
      Census Bureau data. Multivariate linear regression analysis was used to examine
      the relationship between the poverty and education levels and 24-hour urine
      composition. RESULTS: A total of 435 patients were included in the present study.
      Of the 435 patients, 173 were women and 262 were men (40% women), the mean age
      was 52.5 +/- 14.4 years, and the mean body mass index was 28.6 +/- 6.5 kg/m(2).
      The mean percentage of those below the poverty level was 8.2% +/- 6.2%, and the
      mean percentage of those with a high school education or greater was 87.4% +/-
      7.4%. On multivariate linear regression analysis, an increasing local poverty
      level was associated with significant increases in urine calcium (beta = 1.51,
      95% confidence interval [CI] 0.16-2.86). A decreasing local level of education
      (ie, decreasing percentage of those with a high school diploma or greater) was
      associated with significant increases in urine calcium (beta = 1.26, 95% CI 0.10
      2.42), supersaturation of calcium oxalate (beta = 0.04, 95% CI 0.006-0.09), and
      supersaturation of calcium phosphate (beta = 0.013, 95% CI 0.0002-0.03). No other
      associations were found between the poverty and education levels and any urine
      constituents or supersaturations. CONCLUSION: In the present study of patients
      with stone formation, increasing poverty was associated with increased urine
      calcium, and increasing education appeared to be protective by decreasing urine
      calcium and the supersaturation of calcium oxalate and calcium phosphate.
      Additional studies are important to elucidate the mechanisms underlying these
      findings.

PMID- 22608803
TI  - Detection on dynamic changes of endothelial cell specific molecule-1 in acute
      rejection after renal transplantation.
AB  - OBJECTIVE: To investigate the value of dynamic monitoring of endothelial cell
      specific molecule-1 (ESM-1) in diagnosing acute rejection after renal
      transplantation. METHODS: ESM-1 expression was observed in peripheral blood
      circulating endothelial cells and renal allografts after renal transplantation,
      and was compared to the flow cytometry (FCM) results of urine HLA-DR(+)
      lymphocytes. RESULTS: In patients with acute rejection, ESM-1 mRNA and protein
      expression increased significantly (P < .01). Real-time polymerase chain reaction
      detection of ESM-1 mRNA in peripheral blood cells was more sensitive and specific
      than FCM detection of urine HLA-DR(+) lymphocytes. Moreover, real-time PCR
      detection is characterized by convenient sampling and good reproducibility.
      CONCLUSION: ESM-1 is a new marker for endothelial cell activation. However, its
      significance during acute rejection in renal transplantation is still unclear.
      Our study demonstrates that ESM-1 may reflect the degree of endothelial cell
      injury in renal allografts, and that it may serve as a highly sensitive and
      specific marker for acute rejection after renal transplantation.

PMID- 22608804
TI  - Surgical and radiosurgical results of the treatment of cerebral arteriovenous
      malformations.
AB  - Microsurgical resection of a cerebral arteriovenous malformation (AVM) allows for
      an immediate therapeutic cure. Stereotactic radiosurgery (SRS) is a reasonable
      alternative for inoperable or high-risk lesions requiring treatment. Few series
      evaluate overall results that include data from both modalities as they more
      often focus on their treatment method of choice. In this study, we evaluated our
      AVM database of 129 patients seen over the past eight years at our institution:
      73 were treated with microsurgery (57%) while 37 (29%) were treated with SRS. We
      reviewed angiographic obliteration rates, complication rates, and outcome data,
      excluding seven patients treated with SRS as they did not have at least two years
      of angiographic follow-up. Patients undergoing microsurgery had smaller AVM (mean
      2.2 cm compared to 3.5 cm for SRS), a smaller proportion of eloquent AVM (53%
      compared to 83% for SRS), a greater proportion of AVM with superficial drainage
      only (75% compared to 40% for SRS), and more grade 1 and 2 AVM (78% compared to
      17% for SRS). The overall obliteration rate was 80%: 92% for microsurgery and 50%
      for SRS. The latter increased to 92% for AVM <3 cm, but the obliteration rate was
      18% for those AVM >3 cm. Transient complications, including post-SRS hemorrhage,
      were seen in 11% of patients overall (8% after microsurgery, 17% after SRS). At
      follow-up, 53% of patients had improved, 37% remained the same, 7% had become
      worse and 3% had died. As a result of post-SRS hemorrhage, a greater proportion
      of patients was worse or had died after SRS (20%) compared to those who had been
      treated with microsurgery (5%).

PMID- 22608805
TI  - Development of an LC-MS method for determination of three active constituents of
      Shuang-huang-lian injection in rat plasma and its application to the drug
      interaction study of Shuang-huang-lian freeze-dried powder combined with
      levofloxacin injection.
AB  - A sensitive and specific high performance liquid chromatography coupled with mass
      spectrometric (LC-MS) method was developed and validated for the simultaneous
      determination of three main active constituents of Shuang-huang-lian injection
      with and without the combination use of levofloxacin injection in rat plasma.
      After addition of the internal standard rutin, plasma samples were protein
      precipitated with acetonitrile, the chromatographic separation was achieved on a
      Kromasil C18 column (250 mm * 4.6 mm, 5 MUm), using a gradient mobile phase
      system of acetonitrile-water containing 0.05% formic acid. The analytes were
      detected without interference in the selected ion monitoring (SIM) mode with
      positive electrospray ionization. The linear range was 0.04-20 MUg/mL for
      chlorogenic acid, 0.8-400 MUg/mL for baicalin and 0.01-5.0 MUg/mL for phillyrin,
      respectively. The accuracy (relative error, R.E.%) were between -2.7 and 3.4%,
      while the intra-day and inter-day precisions were less than 9.2 and 9.6% for the
      three analytes, respectively. This method was successfully applied to the drug
      interaction study of Shuang-huang-lian freeze-dried powder combined with
      levofloxacin injection after intravenous administration to rats. The results
      indicated that there were obvious differences in the pharmacokinetic behaviors
      after combination compared with only administration of Shuang-huang-lian
      injection.

PMID- 22608806
TI  - Uptake and metabolism of olive oil polyphenols in human breast cancer cells using
      nano-liquid chromatography coupled to electrospray ionization-time of flight-mass
      spectrometry.
AB  - Polyphenols from extra virgin olive oil (EVOO), a main component of the
      Mediterranean diet, have demonstrated repeatedly anti-tumor activity in several
      in vitro and in vivo studies. However, little is known about the efficiency of
      the absorption process and metabolic conversion of these compounds at cellular
      level. In this study, a nano liquid chromatography-electrospray ionization-time
      of flight mass spectrometry (nanoLC-ESI-TOF MS) method was developed to study the
      cellular uptake and metabolism of olive oil phenols in JIMT-1 human breast cancer
      cells. After incubation for different time periods with EVOO-derived phenolic
      extracts, culture media, cytosolic fraction and solid particles fraction were
      separated and analyzed. Most of the free phenols, mainly hydroxytyrosol, its
      secoiridoid derivatives, and the flavonoid luteolin, disappeared in the culture
      media in different ways and at different times. Besides, several metabolites were
      detected in the culture media, fact that may indicate absorption and
      intracellular metabolism followed by rapid cellular export. Low intracellular
      accumulation was observed with only traces of some compounds detected in the
      cytosolic and solid particles fractions. Methylated conjugates were the major
      metabolites detected, suggesting a catalytic action of catechol-O-methyl
      transferase (COMT) in cancer cells.

PMID- 22608807
TI  - A stable-isotope HPLC-MS/MS method to simplify storage of human whole blood
      samples for glutathione assay.
AB  - BACKGROUND: Glutathione is the principal non-protein tripeptide thiol present in
      most mammalian cells and plays an important role in the redox status of
      biological systems. The accurate assessment of reduced glutathione (GSH) status
      as a reliable index of oxidative stress is of research and clinical significance.
      GSH undergoes rapid oxidation after sample collection and this presents a
      challenge. METHODS: Validation of an HPLC-MS/MS assay is reported. Storage
      stability using four variants of a methanolic precipitation with addition of
      stable isotope internal standard at collection is compared to L-serine
      borate/EDTA with perchloric acid precipitation (SBPE). RESULTS: Precipitation
      with methanol and addition of stable isotope on sample collection, combined with
      storage in solution at -70  degrees C showed superior storage stability to SBPE
      and other variants of the methanolic precipitation method up to 99 days.
      CONCLUSIONS: The combination of stable isotope with methanolic precipitation at
      collection, with assay by HPLC-MS/MS provides superior results after storage of
      whole blood samples for at least 99 days.

PMID- 22608808
TI  - Development and validation of a single analytical method for the determination of
      tryptophan, and its kynurenine metabolites in rat plasma.
AB  - It is highly beneficial to monitor the activity of the kynurenine pathway in a
      large series of samples with high accuracy and reliability in a single
      experimental protocol. We have developed a rapid specific solid-phase extraction
      (SPE)-liquid chromatography-electrospray ionization tandem mass spectrometry
      method for assaying tryptophan, kynurenine, kynurenic acid (KYNA), 3
      hydroxyanthranilic acid (3OHAA), anthranilic acid and quinolinic acid (QA) in rat
      plasma. We also evaluated picolinic acid (PA) in this method, but it presented
      with unacceptable validation parameters. The assay involves pre-purification by
      SPE followed by chromatographic separation by C18 reversed phase chromatography.
      Mass spectrometric detection was performed using a mass spectrometer in positive
      and negative electrospray ionization; with a flow rate of 0.2 mL/min and an
      injection volume of 10 MUL. Total run time including sample clean-up was 12 min.
      The assay method was found to be linear (R2 > 0.95) and all the validation
      parameters were within acceptance range. The developed technique also
      demonstrated a significant elevation in plasma tryptophan, kynurenine,
      anthranilic acid and QA, and a significant decrease in KYNA, in rats subjected to
      post-weaning social isolation rearing, a putative animal model of relevance for
      depression and schizophrenia. This method can therefore be applied to measure
      metabolites of the kynurenine pathway in plasma accurately and precisely by LC
      MS/MS, thereby helping to realize new opportunities in pharmacological and
      diagnostic research.

PMID- 22608809
TI  - Intracellular metabolite profiling of platelets: evaluation of extraction
      processes and chromatographic strategies.
AB  - An extraction method for intracellular metabolite profiling should ideally be
      able to recover the broadest possible range of metabolites present in a sample.
      However, the development of such methods is hampered by the diversity of the
      physico-chemical properties of metabolites as well as by the specific
      characteristics of samples and cells. In this study, we report the optimization
      of an UPLC-MS method for the metabolite analysis of platelet samples. The optimal
      analytical protocol was determined by testing seven different extraction methods
      as well as by employing two different LC-MS methods, in which the metabolites
      were separated by using hydrophilic interaction liquid chromatography (HILIC) and
      reversed phase liquid chromatography (RPLC). The optimal conditions were selected
      using the coverage of the platelets' metabolome, the response of the identified
      metabolites, the reproducibility of the analytical method, and the time of the
      analysis as main evaluation criteria. Our results show that methanol-water (7:3)
      extraction coupled with HILIC-MS method provides the best compromise, allowing
      identification of 107 metabolites in a platelet cell extract sample, 91% of them
      with a RSD% lower than 20. A higher number of metabolites could be detected when
      analyzing the platelet samples with two different LC-MS methods or when using
      complementary extraction methods in parallel.

PMID- 22608810
TI  - Nomograms for predicting endometrial cancer recurrence.

PMID- 22608811
TI  - With shortcuts, will quality be cut short?

PMID- 22608812
TI  - Endoscopic visualization of anatomic structures as a support tool in oral surgery
      and implantology.

PMID- 22608814
TI  - Proceedings from the 2011 American Association of Oral and Maxillofacial Surgeons
      research summit.

PMID- 22608815
TI  - Is ultrasonography of the temporomandibular joint ready for prime time? Is there
      a "window" of opportunity?

PMID- 22608816
TI  - Horizontal augmentation of thin maxillary ridge with bovine particulate xenograft
      is stable during 500 days of follow-up: preliminary results of 12 consecutive
      patients.
AB  - PURPOSE: The purpose of our evaluation was to determine the stability of the
      horizontal augmentation of the anterior maxilla using particulate bovine
      xenograft under a membrane. The hypothesis to be tested was that bovine
      particulate graft material is effective for augmenting the narrow ridge of the
      anterior maxilla and can maintain its augmentation dimension within 1 mm over
      time. MATERIALS AND METHODS: A consecutive series of 12 patients who received a
      bovine particulate graft were evaluated in a retrospective manner. Using a
      standardized method, their cone beam scans were measured for width at 3 vertical
      locations preoperatively (T0), immediately after the augmentation (T1), 3 to 6
      months after augmentation and before implant placement (T2), immediately after
      implant placement (T3), and at the longest postoperative point (T4). One
      examiner, who was not involved in the surgical procedures, measured all the
      radiographs. The intraexaminer error approximated 0.2 mm in all areas of
      measurements. A linear mixed effects model was used to determine the stability of
      the augmentation over time. RESULTS: The most coronal aspect of the crest had the
      least width augmentation. The midway region and apical region had the greatest
      width changes (P < .001). Within the sample size, there were no statistically
      significant differences in width changes over time after augmentation was
      performed. CONCLUSIONS: Within the limitations of this sample, horizontal ridge
      augmentation using bovine particulate material under a membrane was stable over
      time in the anterior maxilla.

PMID- 22608817
TI  - Differences in the structure and osteogenesis capacity of the periosteum from
      different parts of minipig mandibles.
AB  - PURPOSE: To compare the structural and cellular differences of the periosteum
      from different parts of the mandible in minipigs by use of histologic and
      immunohistochemical methods to confirm the areas in which periosteal osteogenesis
      in situ can be used to treat mandible defects. MATERIALS AND METHODS: Three
      minipigs were killed, and the left mandible of each was retrieved with the
      periosteum remaining and then fixed, decalcified, and embedded. The specimens
      were cut from the buccal and lingual sides of the ramus, angle, and body of the
      mandible and the mentum. Sections were stained with hematoxylin-eosin and
      antibodies for Stro-1 (stem cell marker) and vWF (endothelial cell marker). For
      each periosteal area, the thickness and number of positive cells for each
      antibody were measured and analyzed. RESULTS: The mentum and mandibular angle
      periostea were thicker than those of the body and ramus. In addition, there were
      more blood vessels in the periostea of the mentum and mandibular body than the
      angle and ramus. There were more Stro-1-positive cells in the ramus periosteum
      than the mentum, body, and angle of the mandibles. CONCLUSIONS: The structure and
      cell populations of the periosteum appear to be site specific. Therefore we
      suggest periosteal osteogenesis in situ to treat mentum and mandibular body
      defects. The periosteum should be preserved as much as possible to guarantee a
      good healing process.

PMID- 22608818
TI  - Why should we start from mandibular fractures in the treatment of panfacial
      fractures?
AB  - PURPOSE: Clinically, the "bottom-up and outside-in" sequence is usually applied
      in the management of panfacial fractures (PFFs). However, findings to prove that
      a sequence initiated from the mandible is reasonable are not available. Our
      objective was to describe the distribution of mandibular fractures in PFFs and
      investigate the basis for initially addressing the mandible when treating PFFs.
      PATIENTS AND METHODS: The data from 107 patients with PFFs from 1998 to 2008 were
      analyzed retrospectively. All cases were treated with the "bottom-up and outside
      in" sequence. RESULTS: The most common sites of mandibular fractures in PFFs were
      the symphysis and condyle. The most common type of fracture was the isolated
      linear fracture. No correlations between fracture type and the incidence of
      mandibular fractures and other fractures in PFFs were observed; however, PFFs
      with simple mandibular fractures had fewer complications and better treatment
      effects than PFFs with complex mandibular fractures. Significant differences
      between mandibular fractures in PFFs and general mandibular fractures were found.
      The type distribution in the former was simpler than that in the latter; the
      severity was also less serious. Most PFF patients treated with the proposed
      sequence presented with satisfactory effects. CONCLUSIONS: Considering the
      important role of the mandible in facial bones, the results have provided
      evidence of the feasibility of the "bottom-up and outside-in" approach in the
      treatment of PFFs. However, some PFFs remain difficult to treat. Thus, additional
      studies are necessary.

PMID- 22608819
TI  - Proposed method for closed reduction of impacted nasal bone fractures using a
      Kirschner wire and a C-arm.
AB  - PURPOSE: Closed reduction is commonly used for the treatment of nasal bone
      fractures. If the fracture is impacted, accurate reduction is difficult.
      Therefore open reduction is often required. MATERIALS AND METHODS: Between
      January 2010 and December 2011, we used a Kirschner wire and a C-arm
      intraoperatively for accurate closed reduction of impacted nasal bone fractures.
      RESULTS: During the follow-up period of 4 weeks to 6 months, all patients had
      satisfactory cosmetic results. CONCLUSIONS: The effectiveness of open reduction
      was obtained without noticeable scarring with our method of closed reduction
      using a Kirschner wire and a C-arm.

PMID- 22608820
TI  - Assessment for treatment of tripod fractures of the zygoma with microcompressive
      screws.
AB  - PURPOSE: The present prospective study sought to evaluate a new rigid internal
      fixation device called a "neck screw," which was applied to patients presenting
      with a tripod fracture of the zygomaticomaxillary complex. PATIENTS AND METHODS:
      Seventeen patients with tripod fractures received surgical treatment from 2007 to
      2010, and had their zygomaticomaxillary complex monofragments fixed using the
      neck screw protocol. The adequacy of fracture reduction, stability of the
      zygomatic monofragment after fixation, cosmetic outcomes, and postoperative
      complications were used to determine the efficacy of this protocol. The stability
      provided by the neck screw was evaluated by computed tomography (CT) scans by
      comparing the immediate postoperative distances between the fractured bone
      segments (control group) with those distances measured on CT scans obtained 5
      weeks later (late group). RESULTS: The average distance observed between the
      fractured ends on the immediate postoperative CT scan was less than 0.58 mm,
      demonstrating adequate fracture reduction. No significant changes were seen in
      these postoperative values after 5 weeks (Wilcoxon test, P = 1.0000),
      demonstrating no displacement of the zygomaticomaxillary complex monofragment
      after fixation using the neck screw. CONCLUSIONS: The proposed surgical treatment
      proved efficient in 17 patients. The fixation stability provided by the neck
      screw was confirmed by subsequent CT scan measurements, statistical analysis, and
      clinical follow-up during the postoperative period, in which patients showed no
      significant associated complications, facial asymmetry, enophthalmos, or
      diplopia.

PMID- 22608821
TI  - Treatment of severe skeletal open bite deformity in patients with Mobius
      syndrome: a report of 3 cases.
AB  - PURPOSE: To investigate the treatment of severe skeletal open bite deformities in
      Mobius syndrome patients. MATERIALS AND METHODS: Three patients aged 17 to 24
      years (2 male patients and 1 female patient) with Mobius syndrome were evaluated
      and treated with preoperative orthodontics, orthognathic surgery, and
      postoperative orthodontic management. One patient was treated by bilateral V
      osteotomies of the mandibular body and one patient with bilateral V osteotomies
      of the mandibular body plus a Le Fort I osteotomy. The third patient had
      bilateral mandibular ramus sagittal split osteotomies in combination with
      maxillary osteotomies. Two of the patients had preoperative electromyographic
      studies on the temporalis and masseter muscles. RESULTS: Postoperative and post
      orthodontic stability was good in 2 cases, whereas a 5-mm anterior open bite
      developed after treatment in 1 case and additional orthodontic management was
      required to re-establish good occlusion. Potential to redevelop anterior open
      bites may likely be related to the functional deficiencies of the muscles of
      mastication and facial paralysis. Two patients who had electromyographic studies
      to evaluate muscle function showed lower-than-normal function of the temporalis
      and masseter muscles. Lower lip ptosis remained a significant esthetic issue in 2
      of 3 patients. CONCLUSIONS: Patients with Mobius syndrome with severe skeletal
      open bite deformities can be treated with combined orthodontic and orthognathic
      surgery; however, there is a tendency for redevelopment of an anterior open bite
      with the surgical and orthodontic techniques used in these cases.

PMID- 22608822
TI  - Dimple creation surgery technique: a review of the literature and technique note.

PMID- 22608823
TI  - A controlled study of a simulated workplace laboratory for adults with attention
      deficit hyperactivity disorder.
AB  - Despite an extant literature documenting that adults with attention
      deficit/hyperactivity disorder (ADHD) are at increased risk for significant
      difficulties in the workplace, there is little documentation of the underlying
      factors associated with these impairments. The main aim of this study was to
      examine specific deficiencies associated with ADHD on workplace performance in a
      simulated workplace laboratory relative to controls. Participants were 56 non
      medicated young adults with DSM-IV ADHD and 63 age- and sex-matched controls
      without ADHD. Participants spent 10h in a workplace simulation laboratory. Areas
      assessed included: (1) simulated tasks documented in a government report (SCANS)
      often required in workplace settings (taxing vigilance; planning; cooperation;
      attention to detail), (2) observer ratings, and (3) self-reports. Robust findings
      were found in the statistically significant differences on self-report of ADHD
      symptoms found between participants with ADHD and controls during all workplace
      tasks and periods of the workday. Task performance was found to be deficient in a
      small number of areas, and there were a few statistically significant differences
      identified by observer ratings. Symptoms reported by participants with ADHD in
      the simulation including internal restlessness, intolerance of boredom and
      difficulty maintaining vigilance were significant and could adversely impact
      workplace performance over the long-term.

PMID- 22608825
TI  - The human genome: a diamond in the rough.

PMID- 22608824
TI  - Intestinal stem cell function in Drosophila and mice.
AB  - Epithelial cells of the digestive tracts of most animals are short-lived, and are
      constantly replenished by the progeny of long-lived, resident intestinal stem
      cells. Proper regulation of intestinal stem cell maintenance, proliferation and
      differentiation is critical for maintaining gut homeostasis. Here we review
      recent genetic studies of stem cell-mediated homeostatic growth in the Drosophila
      midgut and the mouse small intestine, highlighting similarities and differences
      in the mechanisms that control stem cell proliferation and differentiation.

PMID- 22608826
TI  - Measuring nursing competencies in the operating theatre: instrument development
      and psychometric analysis using Item Response Theory.
AB  - BACKGROUND: Concern about the process of identifying underlying competencies that
      contribute to effective nursing performance has been debated with a lack of
      consensus surrounding an approved measurement instrument for assessing clinical
      performance. Although a number of methodologies are noted in the development of
      competency-based assessment measures, these studies are not without criticism.
      RESEARCH AIM: The primary aim of the study was to develop and validate a
      Performance Based Scoring Rubric, which included both analytical and holistic
      scales. The aim included examining the validity and reliability of the rubric,
      which was designed to measure clinical competencies in the operating theatre.
      RESEARCH METHOD: The fieldwork observations of 32 nurse educators and preceptors
      assessing the performance of 95 instrument nurses in the operating theatre were
      used in the calibration of the rubric. The Rasch model, a particular model among
      Item Response Models, was used in the calibration of each item in the rubric in
      an attempt at improving the measurement properties of the scale. This is done by
      establishing the 'fit' of the data to the conditions demanded by the Rasch model.
      RESULTS: Acceptable reliability estimates, specifically a high Cronbach's alpha
      reliability coefficient (0.940), as well as empirical support for construct and
      criterion validity for the rubric were achieved. Calibration of the Performance
      Based Scoring Rubric using Rasch model revealed that the fit statistics for most
      items were acceptable. CONCLUSION: The use of the Rasch model offers a number of
      features in developing and refining healthcare competency-based assessments,
      improving confidence in measuring clinical performance. The Rasch model was shown
      to be useful in developing and validating a competency-based assessment for
      measuring the competence of the instrument nurse in the operating theatre with
      implications for use in other areas of nursing practice.

PMID- 22608827
TI  - Seamless and committed collaboration as an essential factor in effective
      mentorship for nursing students: conceptions of Finnish and British mentors.
AB  - BACKGROUND: The effective mentorship of nursing students requires that mentors
      have a range of personal qualities. However, it is also essential to consider the
      role of other participants, such as colleagues in placement settings and
      educators in educational institutions, as well as the relationship with students.
      OBJECTIVE: This aim of this study was to describe Finnish and British mentors'
      (n=39) conceptions of the factors that affect the provision of effective
      mentorship for pre-registration nursing students in healthcare placements. DESIGN
      AND METHODS: The data in this qualitative study were collected by focus group
      interviews and analysed using a phenomenographical approach. RESULTS: The
      findings highlighted the factors governing seamless and committed collaboration
      with all stakeholders involved in student mentorship. Mentors considered that
      their own advantageous attitude, capabilities and competence, supportive co
      operation with colleagues and lecturers, and enthusiasm and active participation
      of students were all significant factors determining the effectiveness of student
      mentorship. CONCLUSIONS: Nursing organisations and educational units need to
      develop a well-defined and robust partnership strategy for student mentorship,
      which would clarify the roles of all stakeholders. This would help to ensure the
      availability and quality of students' placement learning and mentorship, and
      develop the joint preparation programmes for student mentorship.

PMID- 22608828
TI  - What are the structural conditions of importance to preceptors' performance?
AB  - BACKGROUND: Preceptors play a critical role in the process of developing nursing
      students' knowledge, skills and ability to make independent and critical
      judgments, however relatively little is known about what aspects are associated
      with nurses' performance as preceptors. OBJECTIVES: To investigate structural
      conditions and professional aspects of potential importance to nurses'
      perceptions of their performance as preceptors, and to evaluate the validity and
      reliability of a questionnaire measuring nurses' perceptions of being a
      preceptor. METHODS: The study had a correlational design. Total population
      sampling (N=1720) in a county council district in central Sweden was used to
      screen for nurses with recent preceptor experience, 933 nurses responded
      (response rate 54%), of those 323 nurses fulfilled the inclusion criteria. The
      present findings are based on data from 243 of these subjects. Data were
      collected with a questionnaire and analyzed using multiple regressions analyses,
      exploratory factor analyses and reliability coefficients. RESULTS: The results
      show that aspects such as receiving feedback on the function as a preceptor,
      being able to plan and prepare the clinical education period, receiving support
      from unit managers and having specific supervision education explain 31% of
      nurses' overall view of their performance as preceptors. However, structural
      conditions and professional experiences could not explain preceptors' use of
      reflection and critical thinking when acting as preceptors. These findings are
      discussed within the framework of Kanter's structural theory of power in
      organizations. Further, the psychometric evaluation showed that the questionnaire
      is a valid and reliable instrument for measuring nurses' structural conditions
      for and perceptions of their performance as preceptors. CONCLUSIONS: Structural
      conditions such as feedback and support seemed to strengthen nurses' general view
      of their performance as preceptors but did not seem to facilitate nurses' work
      toward the aim of higher education and helping nursing students develop critical
      thinking.

PMID- 22608829
TI  - Konjac gel as pork backfat replacer in dry fermented sausages: processing and
      quality characteristics.
AB  - The effect of replacing animal fat (0%, 50% and 80% of pork backfat) by an equal
      proportion of konjac gel, on processing and quality characteristics of reduced
      and low-fat dry fermented sausage was studied. Weight loss, pH, and water
      activity of the sausage were affected (P<0.05) by fat reduction and processing
      time. Low lipid oxidation levels were observed during processing time
      irrespective of the dry sausage formulation. The fat content for normal-fat (NF),
      reduced-fat (RF) and low-fat (LF) sausages was 29.96%, 19.69% and 13.79%,
      respectively. This means an energy reduction of about 14.8% for RF and 24.5% for
      LF. As the fat content decreases there is an increase (P<0.05) in hardness and
      chewiness and a decrease (P<0.05) in cohesiveness. No differences were
      appreciated (P>0.05) in the presence of microorganisms as a result of the
      reformulation. The sensory panel considered that NF and RF products had
      acceptable sensory characteristics.

PMID- 22608830
TI  - The effect of iodine salts on lipid oxidation and changes in nutritive value of
      protein in stored processed meats.
AB  - The aim was to assess the effect of iodine salts (KI or KIO(3)) on lipid
      oxidation as well as changes in the availability of lysine and methionine and
      protein digestibility in frozen-stored processed meats. Three types of iodine
      salt carriers were used: table salt, wheat fiber and soy protein isolate. The
      results showed no catalytic effect of iodine salts on lipid oxidation in stored
      processed meats. The application of a protein isolate and wheat fiber resulted in
      the inhibition of lipid oxidation in meatballs. During storage of meat products
      the contents of available lysine and methionine as well as protein digestibility
      were decreased. The utilization of wheat fiber as an iodine salt carrier had a
      significant effect on the reduction of lysine losses. No protective properties
      were found for the wheat fiber or soy protein isolate towards methionine.

PMID- 22608831
TI  - Quality considerations with high pressure processing of fresh and value added
      meat products.
AB  - Pressure can be applied by high hydrostatic pressure, better known as high
      pressure processing (HPP), or by hydrodynamic pressure (HDP) in the form of
      shockwaves to alter quality parameters, such as shelf-life and texture of meat
      and meat products. The aim of this review is to give an overview of the use of
      pressure in the meat industry and to highlight its usage as a method to
      inactivate microorganisms but also a novel strategy to alter the structure and
      the quality parameters of meat and meat products. Benefits and possibilities of
      the technologies are presented, as well as how to overcome undesired product
      changes caused by HPP. The use of hydrodynamic shockwaves is briefly described
      and a promising newly developed industrial prototype for the generation of
      shockwaves by underwater explosion is presented.

PMID- 22608832
TI  - Amino acid sequence of myoglobin from white-tailed deer (Odocoileus virginianus).
AB  - Our objective was to determine the primary structure of white-tailed deer
      myoglobin (Mb). White-tailed deer Mb was isolated from cardiac muscles employing
      ammonium sulfate precipitation and gel-filtration chromatography. The amino acid
      sequence was determined by Edman degradation. Sequence analyses of intact Mb as
      well as tryptic- and cyanogen bromide-peptides yielded the complete primary
      structure of white-tailed deer Mb, which shared 100% similarity with red deer Mb.
      White-tailed deer Mb consists of 153 amino acid residues and shares more than 96%
      sequence similarity with myoglobins from meat-producing ruminants, such as
      cattle, buffalo, sheep, and goat. Similar to sheep and goat myoglobins, white
      tailed deer Mb contains 12 histidine residues. Proximal (position 93) and distal
      (position 64) histidine residues responsible for maintaining the stability of
      heme are conserved in white-tailed deer Mb.

PMID- 22608833
TI  - Road transport of cattle, swine and poultry in North America and its impact on
      animal welfare, carcass and meat quality: a review.
AB  - This paper reviews the effects of road transport on the welfare, carcass and meat
      quality of cattle, swine and poultry in North America (NA). The main effects of
      loading density, trailer microclimate, transport duration, animal size and
      condition, management factors including bedding, ventilation, handling,
      facilities, and vehicle design are summarized by species. The main effects listed
      above all have impacts on welfare (stress, health, injury, fatigue, dehydration,
      core body temperature, mortality and morbidity) and carcass and meat quality
      (shrink, bruising, pH, color defects and water losses) to varying degrees. It is
      clear that the effect of road transport is a multi-factorial problem where a
      combination of stressors rather than a single factor is responsible for the
      animal's well-being and meat quality post transport. Animals least fit for
      transport suffer the greatest losses in terms of welfare and meat quality while
      market ready animals (in particular cattle and pigs) in good condition appear to
      have fewer issues. More research is needed to identify the factors or combination
      of factors with the greatest negative impacts on welfare and meat quality
      relative to the species, and their size, age and condition under extreme
      environmental conditions. Future research needs to focus on controlled scientific
      assessments, under NA conditions, of varying loading densities, trailer design,
      microclimate, and handling quality during the transport process. Achieving
      optimal animal well-being, carcass and meat quality will entirely depend on the
      quality of the animal transport process.

PMID- 22608834
TI  - Recombinant B-type natriuretic peptide nesiritide attenuates vascular remodelling
      by reducing plasma aldosterone in rabbits.
AB  - BACKGROUND: This study was designed to investigate the effect of nesiritide, a
      recombinant B-type natriuretic peptide (BNP), on plasma aldosterone and vascular
      remodelling following balloon-induced endothelial injuries to the iliac arteries.
      METHODS: Twenty-four male New Zealand rabbits were divided into nesiritide
      (0.1mg/kg/day, sc, for 4 weeks, n=12) and saline-treated control group (n=12). A
      balloon catheter was inserted to the right iliac artery to induce endothelia
      injuries. Plasma aldosterone was measured before and 28 days after the treatment
      by radioimmunoassay. RESULTS: The area under internal elastic membrane (657.1+/
      129.6 vs 486.7+/-124.0MUm(2), P=0.02) and the area under external elastic
      membrane (1506.2+/-188.3.9 vs 1185.0+/-202.9MUm(2), P=0.02) in the nesiritide
      group were greater than in the control group. The stenosis ratio in the
      nesiritide group was lower than in the control group (20.1+/-6.2% vs 39.6+/-9.5%,
      P=0.01). The plasma levels of aldosterone (2.03+/-0.31 vs 3.00+/-0.29ng/L,
      P<0.01) in the nesiritide group was lower than in the control group. Pearson's
      correlation analysis showed a positive correlation between the levels of plasma
      aldosterone and the stenosis ratio of the injured right iliac arteries (r=0.622,
      P=0.002). CONCLUSION: Nesiritide treatment reduced stenosis ratio of the rabbit
      iliac artery following balloon-induced endothelial injuries, and the reduced
      stenosis ratio was associated with a reduction in the plasma aldosterone
      concentrations.

PMID- 22608835
TI  - Hemodialysis Reliable Outflow (HeRO) device in end-stage dialysis access: a
      decision analysis model.
AB  - BACKGROUND: The Hemodialysis Reliable Outflow (HeRO) dialysis access device is a
      permanent tunneled dialysis graft connected to a central venous catheter and is
      used in patients with end-stage dialysis access (ESDA) issues secondary to
      central venous stenosis. The safety and effectiveness of the HeRO device has
      previously been proven, but no study thus far has compared the cost of its use
      with tunneled dialysis catheters (TDCs) and thigh grafts in patients with ESDA.
      MATERIALS AND METHODS: A decision analytic model was developed to simulate
      outcomes for patients with ESDA undergoing placement of a HeRO dialysis access
      device, TDC, or thigh graft. Outcomes of interest were infection, thrombosis, and
      ischemic events. Baseline values, ranges, and costs were determined from a
      systematic review of the literature. Total costs were based on 1 year of post
      procedure outcomes. Sensitivity analyses were conducted to test model strength.
      RESULTS: The HeRO dialysis access device is the least costly dialysis access with
      an average 1-year cost of $6521. The 1-year cost for a TDC was $8477. A thigh
      graft accounted for $9567 in a 1-year time period. CONCLUSIONS: The HeRO dialysis
      access device is the least costly method of ESDA. The primary determinants of
      cost in this model are infection in TDCs and leg ischemia necessitating
      amputation in thigh grafts. Further study is necessary to incorporate patient
      preference and quality of life into the model.

PMID- 22608836
TI  - The rising incidence of arthroscopic superior labrum anterior and posterior
      (SLAP) repairs.
AB  - BACKGROUND: Superior labrum anterior-posterior (SLAP) lesions of the shoulder
      that require surgical repair are relatively uncommon. However, recent
      observations suggest that there may be a rise in the incidence of SLAP lesion
      repair. MATERIALS AND METHODS: The Statewide Planning and Research Cooperative
      Systems (SPARCS) database from the New York State Department of Health was used
      to acquire data for all outpatient ambulatory surgery procedures that were
      performed in New York State from 2002 to 2010. The data were reviewed and
      analyzed to compare the incidence of arthroscopic SLAP lesion repairs relative to
      other outpatient surgical procedures. RESULTS: Within New York State, from 2002
      to 2010, the number of all ambulatory surgical procedures increased 55%, from
      1,411,633 to 2,189,991. Correspondingly, the number of ambulatory orthopedic
      procedures increased 135%, from 118,126 to 278,136. In comparison, the number of
      arthroscopic SLAP repairs increased 464%, from 765 to 4,313 (P < .0001). This
      represented a population-based incidence of 4.0/100,000 in 2002 and 22.3/100,000
      in 2010. The mean age of patients undergoing arthroscopic SLAP repair in 2002 was
      37 +/- 14 years. The mean age in 2010 was 40 +/- 14 years (P < .0001).
      CONCLUSIONS: The data suggest a substantial increase in the number of
      arthroscopic SLAP repairs that is significantly more rapid than the rising rate
      of outpatient orthopedic surgical procedures. In addition, there is a significant
      increase in the age of patients who are being treated with arthroscopic SLAP
      repairs.

PMID- 22608837
TI  - Positive life orientation in old age: a 15-year follow-up.
AB  - BACKGROUND: Positive life orientation (PLO) is considered an important dimension
      of successful aging. AIM: To investigate how self-reported PLO changed among home
      dwelling people from age 70 to 80 and 85 years. STUDY DESIGN: A prospective,
      population-based 15-year follow-up study of the age cohort of 70-year-olds living
      in the city of Turku, Finland. SUBJECTS AND METHODS: The data were collected in
      1991 by a postal questionnaire that was sent to all residents of Turku, Finland,
      born in 1920 (N=1530). Follow-ups using the same procedure were conducted in 2001
      and 2006. PLO was assessed with the following items: life satisfaction, feeling
      needed, having plans for the future, having zest for life, feeling depressed, and
      suffering from loneliness. We created a PLO score from the answers to these
      questions, where 1 represented the best PLO and 0 the poorest. RESULTS: At
      baseline, the participants showed rather high levels of positive life orientation
      (PLO total score 0.83). PLO declined markedly after the 70-year-old participants
      reached the age of 80 and 85 years (p<.001). However, depressive feelings
      remained quite stable. The decrease was similar among men and women except for
      the items suffering from loneliness and feeling needed. At age 70 and 80 years
      women suffered more from loneliness than men, while men experienced feeling
      needed more than women. CONCLUSIONS: Positive life orientation declines during
      old age, especially from age 70 to 80 years. Thereafter the decline is less steep
      except for changes in future plans and feeling needed.

PMID- 22608838
TI  - Evaluation and management of oropharyngeal dysphagia in different types of
      dementia: a systematic review.
AB  - INTRODUCTION: Dysphagia, or swallowing impairment, is a growing concern in
      dementia and can lead to malnutrition, dehydration, weight loss, functional
      decline, and fear of eating and drinking as well as a decrease in quality of life
      (QOL). OBJECTIVE: The aim of this article is to do a systematic review of the
      literature to determine the patterns of swallowing deficits in different types of
      dementia and to look at the usefulness of different diagnostic and management
      strategies. METHODS: An electronic literature search was done using five
      electronic databases from 1990 to 2011. One thousand and ten records were
      identified and 19 research articles met the inclusion criteria. These studies
      were heterogeneous in design and methodology, type of assessment and outcomes, so
      only descriptive analysis (narrative reporting) was possible. RESULTS: Prevalence
      of swallowing difficulties in patients with dementia ranged from 13 to 57%.
      Dysphagia developed during the late stages of frontotemporal dementia (FTD), but
      it was seen during the early stage of Alzheimer's dementia (AD). Limited evidence
      was available on the usefulness of diagnostic tests, effect of postural changes,
      modification of fluid and diet consistency, behavioral management and the
      possible use of medications. Use of Percutaneous Endoscopic Gastrostomy (PEG)
      tubes in advanced dementia, did not show benefit with regards to survival,
      improvement in QOL, or reduction in aspiration pneumonia. Significant gaps exist
      regarding the evidence for the evaluation and management of dysphagia in
      dementia.

PMID- 22608839
TI  - Severe community-acquired pneumonia caused by adenovirus type 11 in
      immunocompetent adults in Beijing.
AB  - BACKGROUND: Severe community-acquired pneumonia (CAP) due to human adenoviruses
      (HAdVs) in immunocompetent adults has raised concerns. OBJECTIVE: To describe the
      clinical, laboratorial, and radiological characteristics of adenovirus pneumonia
      and detect the type and diversity of human adenoviruses that caused acute
      respiratory distress syndrome (ARDS) in Beijing. STUDY DESIGN: An etiological
      study of adult community-acquired pneumonia was carried out prospectively at
      Beijing Chao-Yang Hospital. A total of 18 cases with laboratory-confirmed
      adenovirus infections in 487 cases with CAP were observed clinically. The viral
      type and phylogenetic analysis were tested by polymerase chain reaction (PCR).
      RESULTS: Patients with adenovirus pneumonia typically reported flu-like symptoms.
      Some of them developed shortness of breath or severe dyspnea on 6 days after
      disease onset. The patients with ARDS usually present dyspnea, higher level of
      serum muscle enzymes and bilateral, mutilobal consolidation and patchy/ground
      glass opacities. HAdVs type was detected in 17 samples and all of them belonged
      to species B (HAdV-11, 7, 3 and 14). Among them, HAdV-11 was most frequently
      (10/17), followed by HAdV-7 (5/17). Phylogenetic analysis of the partial penton
      nucleotide confirmed a close relationship with stains circulating in the Beijing
      region. CONCLUSIONS: Our identification of severe respiratory illness due to
      adenovirus, especially type 11 may highlight the need for rapid diagnosis and
      improved surveillance, which may assist with targeted development of antiviral
      agents or type-specific vaccines.

PMID- 22608840
TI  - Molecular evidence of St. Louis encephalitis virus infection in patients in
      Buenos Aires, Argentina.
AB  - We report two cases of St. Louis encephalitis where the virus was detected in
      patients' sera directly by molecular techniques allowing subsequent typing.
      Phylogenetic analysis of both samples showed that NS5 sequences clustered with
      viruses previously classified as genotype III.

PMID- 22608841
TI  - Human parvovirus B19 genotype 3 associated with chronic anemia after stem cell
      transplantation, missed by routine PCR testing.

PMID- 22608842
TI  - Prevalence of hepatitis B virus infection among tuberculosis patients with or
      without HIV in Goiania City, Brazil.
AB  - BACKGROUND: Hepatitis B virus (HBV) and tuberculosis (TB) represent major public
      health problems. There is currently little data on HBV infection among TB
      patients with and without human immunodeficiency virus (HIV). OBJECTIVES: To
      assess HBV prevalence among TB patients with and without HIV. STUDY DESIGN: From
      April 2008 to March 2010, a cross-sectional study was conduct among TB patients
      attended at a reference hospital in Goiania City, Brazil. The participants were
      tested for serological markers of HBV infection and HIV antibodies. HBV DNA was
      detected in HBsAg-positive samples, and also in HBsAg-negative/anti-HBc-positive
      samples to look for HBV occult infection. RESULTS: Of 425 patients, 402 (94.6%)
      agreed to participate in the study. The overall prevalence of HBV (HBsAg and/or
      anti-HBc positive) and HIV infections were 25.6% (103/402) and 27.6% (111/402),
      respectively. A higher HBV infection rate was found among HIV-infected patients
      (36.9%; 41/111) compared to patients infected with TB only (20.0%; 57/285). A
      multivariate analysis of risk factors showed that age >= 50 years (p=0.03), non
      injecting (p<0.01) and injecting (p<0.01) drugs use were associated with HBV
      infection. Among the HBsAg-positive samples (n=13), HBV DNA was detected in 10
      (76.9%) samples. Of the 90 anti-HBc-positive samples, 13 were HBV DNA positive
      (with very low levels) resulting in an occult HBV infection rate of 14.4%. PCR
      RFLP was successfully performed in 20 HBV DNA-positive samples: 15 were genotype
      A and 5 were genotype D. CONCLUSIONS: HBV infection was common, particularly
      among this with HIV infection.

PMID- 22608843
TI  - Unusual localizations of sentinel lymph nodes in early stage cervical cancer: a
      review.
AB  - OBJECTIVE: The aim of this study was to systematically determine the frequency of
      unusual localizations of sentinel lymph node in patients with early stage
      cervical cancer. METHODS: We performed a comprehensive computer literature search
      of English and French language studies in human subjects on sentinel node
      procedures in PUBMED database up to December 2010. For each article two reviewers
      independently performed data extraction using a standard form to determine the
      route of unusual lymphatic spread of sentinel procedures in cervical cancer.
      RESULTS: According to our search, 83.7% of detected sentinel lymph nodes in
      patients with cervical cancer were in expected localizations (i.e., external
      iliac, obturator, internal iliac or interiliac). The unusual localizations were:
      6.6% in the common iliac chain, 4.31% parametrial, 1.26% sacral, 2% in the lower
      para-aortic area and 0.07% in the inguinal chain. CONCLUSION: The unusual
      localizations of sentinel lymph nodes impose to the gynecologic surgeons to be
      able to perform lymph node dissection in all the territories potentially
      affected.

PMID- 22608844
TI  - Invasive Brevundimonas vesicularis bacteremia: two case reports and review of the
      literature.
AB  - There are few reports of invasive infections caused by Brevundimonas vesicularis.
      We report two cases of B. vesicularis bacteremia confirmed by culture and 16S
      rRNA sequence analysis with highly variable sensitivity to broad-spectrum
      antibiotics. Initial empiric therapy with anti-pseudomonal antibiotics plus
      trimethoprim-sulfamethoxazole for hospital-acquired B. vesicularis infections
      should be considered.

PMID- 22608845
TI  - Systemic lupus erythematosus with initial presentation of empyematous pleural
      effusion in an elderly male patient: a diagnostic challenge.
AB  - Systemic lupus erythematosus (SLE) poses great difficulty in making an early
      diagnosis in elderly males, often presenting with atypical manifestations. Acute
      onset of empyematous pleural effusion has rarely been seen. Herein, we report a
      66-year-old man with SLE presenting with rapid progression of bilateral pleural
      effusion. Diagnostic thoracocentesis disclosed neutrophil-predominant exudates
      and chest computed tomography revealed multiple loculated pleural effusions.
      Nevertheless, optimal antibiotic therapy plus surgical decortication of the
      pleura did not improve his condition. The diagnosis of SLE was readily
      established after LE cells were accidentally found in the pleural effusion. Large
      amounts of pleural effusion subsided soon after high dose corticosteroid therapy.

PMID- 22608846
TI  - Killed but metabolically active vaccines.
AB  - Beginning in the 20th century and continuing into the new millennia, vaccines
      against numerous diseases have had an unquestioned principal role of both
      enhancing the quality of life and increasing life expectancy (Rappuoli R, Mandl
      CW, Black S, De Gregorio E: Vaccines for the twenty-first century society. Nat
      Rev Immunol 2011, 11:865-872). Despite this success and the development of
      sophisticated new vaccine technologies, there remain multiple infectious diseases
      including tuberculosis, malaria and AIDS that await an effective prophylactic
      vaccine. In addition, there have been recent clinical successes among individuals
      with cancer using vaccine treatment strategies-so-called therapeutic vaccines
      that stimulate tumor specific immunity and increase survival (Kantoff PW, Higano
      CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R,
      Sims RB, et al.: Sipuleucel-T immunotherapy for castration-resistant prostate
      cancer. New Engl J Med 2010, 363:411-422). Here we summarize a new class of
      vaccines termed Killed But Metabolically Active (KBMA). KBMA vaccines are whole
      pathogenic or attenuated organisms killed through photochemical inactivation and
      cannot cause disease, yet retain sufficient metabolic activity to initiate a
      potent immune response. KBMA vaccines have two broad applications. First,
      recombinant KBMA vaccines encoding selected antigens relevant to infectious
      disease or cancer can be used to elicit a desired immune response. In the second
      application, KBMA vaccines can be derived from attenuated forms of a targeted
      pathogen, allowing for the presentation of the entire antigenic repertoire to the
      immune system, of particular importance when the correlates of protection are
      unknown.

PMID- 22608847
TI  - Foam production--ratio between foaminess and rate of foam decay.
AB  - Foams are usually characterized by the foaminess of their surfactant solutions
      and the rate of foam decay. These two properties have been described many times
      separately in the literature. There is a certain correlation between them, which
      can vary depending on the type and the concentration of the surfactants, the
      method of foam generation, etc. We suggest with this work a new parameter
      unifying foaminess and rate of foam decay. The foam production is a parameter,
      which is a ratio between foaminess and rate of foam decay. It was shown an
      example how foaminess, rate of foam decay and foam production depends on C/CMC (C
      - surfactant concentration, CMC - critical micelle concentration) of aqueous
      solutions of sodium octylsulfate (SOS). In addition, it has been stressed that a
      number of scientific problems on transient foams can be solved by means of the
      approach pointed out by this study. An example, for which the foam production
      depends on the way of foam generation, is given. A new criterion for assessing
      the ability of the surfactants to stabilize foams has been suggested. Thus, the
      stronger surfactants do not always produce more stable transient foams than the
      weaker ones, as usually is assumed.

PMID- 22608848
TI  - Ultra-fast method to synthesize mesoporous magnetite nanoclusters as highly
      sensitive magnetic resonance probe.
AB  - An ultra-fast method to synthesize mesoporous magnetite (Fe(3)O(4)) nanoclusters
      is reported. These mesoporous magnetite can be used as a highly sensitive
      magnetic resonance imaging (MRI) probe. The nanoclusters were synthesized by
      reducing iron (III) acetylacetonate with hydrazine in ethylene glycol under
      microwave irradiation and only 5 min was needed in the synthesis. The diameter of
      the nanoclusters could be controlled effectively between 75 nm and 115 nm by
      increasing the amount of iron (III) acetylacetonate. Brunauer-Emmett-Teller (BET)
      results reveal a mesoporous structure and a large surface area of 72.3 m(2) g(
      1). Cytotoxicity test performed in HepG2 cell line indicated that the as-prepared
      nanoclusters were non-cytotoxic. The nanoclusters exhibited an enhanced T(2)
      relaxivity value of 417.4+/-29.9 s(-1) mM(-1). In vitro and in vivo MRI confirmed
      the high sensitivity of the magnetite nanoclusters as MRI probe. The
      biodistribution of the nanoclusters in rat liver and spleen after intravenous
      injection was also investigated.

PMID- 22608849
TI  - The most frequently cited adsorption research articles in the Science Citation
      Index (Expanded).
AB  - The 126 most frequently cited articles published in the adsorption field between
      1900 and 2011 were identified and characterized using the Science Citation Index
      (Expanded). The data analyzed cover a range of publication years, journals, Web
      of Science categories, authors, institutions, countries/territories, life
      citation cycle curves, and characteristics of frequently cited articles. The 126
      most-frequently-cited articles were each cited an average of 1014 times, ranging
      from 502 to 9922 citations per article from 1918 to 2006; 80% of these articles
      were published after 1970. Fifty-five journals were represented, led by the
      Journal of the American Chemical Society, and followed by Science and Nature.
      Three categories out of the 35 Web of Science categories constituted 60% of the
      citations. The three categories were: physical chemistry, multidisciplinary
      chemistry, and multidisciplinary sciences. Thirteen of the authors contributed
      three or more articles. Harvard University, the Massachusetts Institute of
      Technology, and the University of Washington led the list of 107 institutions,
      while the United States led the list of 17 countries/territories, comprising more
      than half of the articles. Collaboration among the top authors was a frequent
      occurrence, while inter-institutional collaboration and national collaboration
      was not obvious among the topmost articles. Moreover, the citation patterns as a
      function of time varied widely among the topmost articles. As evidenced by
      citation life cycles, the well known BET and Langmuir isotherms have received
      considerable attention during the study period, and will probably continue to be
      popular in the adsorption field. Some emerging hotspots are likely to receive
      particular attention in the near future; these include the new family of "M41S"
      materials, pseudo-second-order kinetic models, and the nudged elastic band
      method.

PMID- 22608850
TI  - Aqueous synthesis and characterization of glutathione-stabilized beta-HgS
      nanocrystals with near-infrared photoluminescence.
AB  - A simple, rapid and green aqueous approach to near-infrared (NIR)-emitting beta
      HgS nanocrystals (NCs) was demonstrated for the first time by using glutathione
      (GSH) as the stabilizer at room temperature. The resulting HgS NCs with zinc
      blend structure exhibited strong quantum size effect, and the emission peak could
      be tuned in a wide NIR region from ca. 775 to 1041 nm. As compared with early
      achievements, the emission intensity of GSH-stabilized HgS NCs enhanced, with the
      maximum quantum yield reaching ~2.8%. It was also found that the stability of the
      GSH-HgS NCs was improved noticeably, the PL peak red-shifting only 9 nm and 23 nm
      after stored at 4 degrees C for 4 months and 25 degrees C for 7 days,
      respectively. The better stability of the HgS NCs was elucidated by FT-IR due to
      the multiple coordination of GSH molecule to surface Hg of the NCs. The emission
      range of GSH-stabilized HgS NCs was located between the visible region (500-800
      nm) and IR region (1000-1600 nm) of HgS NCs as reported previously, extending the
      emission region of HgS nanomaterial. Therefore, the continuous emission from
      visible to IR spectral ranges provided HgS material more potential applications.

PMID- 22608851
TI  - The post ACOSOG Z0011 era: does our new understanding of breast cancer really
      change clinical practice?
AB  - BACKGROUND: The ACOSOG Z0011 trial (Z0011) expanded our thinking about breast
      cancer (BC) and showed that limited metastatic disease left behind in the axilla
      did not compromise oncological safety in a selected group of patients. The aim of
      the current study was to assess the potential impact of Z0011 on clinical
      practice by testing the applicability of its criteria to a European patient
      population. METHODS: We reviewed a consecutive series of 389 sentinel lymph node
      biopsies (SLNB) performed for invasive BC at the University Hospital Basel
      between 2003 and 2009 (65.6% of all surgically treated patients, n = 593).
      RESULTS: When compared to the axillary lymph node dissection (ALND) arm of Z0011,
      our patients had significantly less advanced LN involvement (>= 3 LN: 8.5% vs.
      21.0%, p = 0.048). Thirty-five patients (9.0%) met the Z0011 inclusion criteria
      and had 1-2 SLNs with macrometastases (5.9% of all surgically treated BC
      patients). If the inclusion criteria of Z0011 had been applied, a considerable
      number of LNs would have been missed in two cases (0.5% of all SLNBs).
      CONCLUSIONS: The application of the Z0011 led to the omission of completion ALND
      in less than 10% of all SLNB procedures (<6% of all surgically treated BC
      patients); therefore, we do not think that the perception of Z0011 as "practice
      changing" is justified. On the other side, skeptics of the routine implementation
      of the Z0011 protocol may overestimate its potential hazards. When performing a
      thorough preoperative clinical axillary staging, the number of patients who would
      have been undertreated is minimal.

PMID- 22608852
TI  - A prospective randomised study of minimally invasive midvastus total knee
      arthroplasty compared with standard total knee arthroplasty.
AB  - INTRODUCTION: Proposed advantages of minimally invasive surgery include shorter
      hospital stay, less blood loss, and a greater range of motion but potential
      concerns are raised about both prolonged learning curves and a compromise in
      exposure leading to implant malposition. PATIENTS AND METHODS: This powered study
      evaluates the outcomes of 80 patients randomised to have mini-midvastus (MMV)
      approach or standard medial parapatellar (MPP) approach. Rehabilitation protocols
      and discharge criteria were standardised. Patients were discharged home directly,
      capable of safe independent care. Validated outcome measures were recorded post
      operatively at intervals up to 1 year. Independent, blinded review of post
      operative x-rays was obtained. RESULTS: Length of stay was similar in the MMV and
      MPP groups (median 3.73 days vs. 3.75 days). No statistically significant
      differences were detected in either the demographic data or any intra-operative
      variable apart from blood loss and incision length. No statistically significant
      difference in clinical outcome measures (Oxford/Knee Society Scores) or
      radiographic analysis was observed. CONCLUSION: The MMV approach does not appear
      to confer any clinically significant benefit apart from a smaller surgical scar,
      compared to the MPP surgical technique. Level of evidence I: randomised control
      trial. R.E.C. 040301.

PMID- 22608853
TI  - An evidence-based recommendation for the inclusion of specific local intrinsic
      factors in the study of knee osteoarthritis.
AB  - OBJECTIVE: Adequate characterization of the mechanical environment of the knee
      with osteoarthritis (OA) is important. These local intrinsic factors are
      difficult to measure and there is little evidence to guide their selection. This
      study makes an evidence-based recommendation for the inclusion of specific
      factors in the future study of knee OA. METHOD: Forty-six subjects with knee OA
      were examined. Observed function was measured by the Timed Chair Rise (TCR). Self
      reported function was measured by the WOMAC Function Scale and pain was measured
      by the WOMAC Pain Scale. Local intrinsic factors measured included varus/valgus
      alignment, anterior/posterior (A/P) laxity, proprioception, isometric knee
      extension (KE) strength, isometric knee flexion (KF) strength, and knee range of
      motion (ROM). RESULTS: Factors were recommended for inclusion in future research
      if they were significantly correlated with at least one measure of function or
      pain and if the factor made a significant unique contribution to a regression
      model when more than one local intrinsic factor was correlated with the same
      measure of function or pain. Alignment was correlated with pain (r=0.48, p=0.001)
      and WOMAC function (r=0.38, p=0.009). A/P laxity was correlated with pain
      (r=0.30, p=0.04) and WOMAC function (r=0.37, p=0.01). Knee ROM was correlated to
      WOMAC function (r=-0.35, p=0.02). KE strength was correlated with TCR (r=0.32,
      p=0.03). Alignment made a significant contribution to prediction of pain
      (p=0.003). A/P laxity (p=0.004) and ROM (p=0.008) made a significant contribution
      to WOMAC function. CONCLUSION: We recommend future knee OA studies include the
      variables varus/valgus alignment, A/P laxity, ROM, and KE strength.

PMID- 22608854
TI  - Synthesis of benzimidazoles bearing oxadiazole nucleus as anticancer agents.
AB  - Starting from 4-(1H-benzo[d]imidazol-2-yl)-4-oxobutanehydrazide (1), twenty new 1
      (1H-benzo[d]imidazol-2-yl)-3-(1,3,4-oxadiazol-5-substituted derivatives-2
      yl)propan-1-ones (1b-A(7)(-)(26)) were synthesized under microwave irradiation in
      good yields. Further, compound 1b-A(7) was reacted with different secondary
      amines under microwave irradiation to produce five novel 1-(1H-benzo[d]imidazol-2
      yl)-3-(5-(methyl substituted)-1,3,4-oxadiazol-2-yl)propan-1-ones (1b-A(7a)(
      )(e)). The title compounds were screened for their in vitro anticancer activity
      at National Cancer Institute (NCI), USA; at a single dose (10 MUM) in NCI 60 cell
      line panel and results showed significant to good anticancer activity. One
      compound, 1b-A(18) (NSC: 759205), 1-(1H-benzo[d]imidazol-2-yl)-3-(5-(2,4
      dichlorophenyl)-1,3,4-oxadiazol-2-yl)propan-1-one, emerged as lead compound; it
      was selected for five-dose level screening and found to have significant growth
      inhibition activity.

PMID- 22608855
TI  - Iridoid glucosides from Nyctanthes arbortristis result in increased reactive
      oxygen species and cellular redox homeostasis imbalance in Leishmania parasite.
AB  - We report here the effect of iridoid glucosides, isolated from Nyctanthes
      arbortristis, on redox homeostasis of Leishmania parasite. These compounds led to
      an increase in reactive oxygen species by inhibiting a crucial enzyme of redox
      metabolism of the parasite. Our experiments clearly showed that these compounds
      are highly active as antileishmanial agents. The in vitro experiments on intra
      macrophageal amastigotes showed significant killing of parasite even at very low
      concentration. Determination of mechanism of action of iridoid glucosides showed
      that increased ROS level leads to oxidative stress, cell membrane damage and
      apoptosis of Leishmania sp. Our cellular toxicity assays on Human embryonic
      kidney (HEK 293) and mouse macrophage (J774A.1) cell lines showed these compounds
      to be very safe for therapeutics application.

PMID- 22608856
TI  - Photochemical internalisation: the journey from basic scientific concept to the
      threshold of clinical application.
AB  - Efficient delivery of therapeutic agents to subcellular targets is a major
      challenge in pharmacology. Physical properties including size and charge may
      adversely affect the cellular uptake of molecules, and consequently reduce the
      accessibility of intracellular targets. For example macromolecules, which do not
      pass freely through the phospholipid membrane, are internalised via endocytosis
      and subsequently retained in endosomes or lysosomes before enzymatic degradation
      or cell efflux. Photochemical internalisation (PCI) is a novel drug delivery
      technology based on light-activated release of biologically active compounds
      retained within endosomes/lysosomes. PCI is founded upon the principle of
      photodynamic therapy (PDT), which uses light to activate photosensitisers to
      ultimately produce reactive oxygen species (ROS) and cause local damage/cell
      death. In PCI, photosensitisers are selectively localised in endosomal/lysosomal
      membranes. PCI triggers membrane rupture facilitating release and delivery of
      endocytosed molecules to intracellular targets.

PMID- 22608857
TI  - Introducing the Maastricht Acute Stress Test (MAST): a quick and non-invasive
      approach to elicit robust autonomic and glucocorticoid stress responses.
AB  - Stress-related research has employed several procedures to activate the human
      stress system. Two of the most commonly used laboratory paradigms are the Trier
      Social Stress Test (TSST) and the Cold Pressor Test (CPT). We combined their most
      stressful features to create a simple laboratory stress test capable of eliciting
      strong autonomic and glucocorticoid stress responses. In comparison with the CPT
      and its variations, our stress tool (labeled the Maastricht Acute Stress Test;
      MAST) was found to yield superior salivary cortisol responses, while being
      equally effective in eliciting subjective stress reactions and (systolic and
      diastolic) blood pressure increases (study 1; N=80). In study 2 (N=20), we
      directly compared the effectiveness of the MAST and TSST and found that both
      methods elicited similar subjective, salivary alpha-amylase, and salivary
      cortisol stress responses. Finally, we developed and evaluated an appropriate no
      stress control version of the MAST that was similar to the stress version,
      although it did not comprise stressful components (study 3; N=40). Collectively,
      our results confirm the effectiveness of the MAST in terms of subjective,
      autonomic, and--most importantly--glucocorticoid stress responses. Thus, as a
      brief and simple stress protocol, the MAST holds considerable promise for future
      research.

PMID- 22608858
TI  - Solar cycle predicts folate-sensitive neonatal genotypes at discrete phases of
      the first trimester of pregnancy: a novel folate-related human embryo loss
      hypothesis.
AB  - Folate, a key periconceptional nutrient, is ultraviolet light (UV-R) sensitive.
      We therefore hypothesise that a relationship exists between sunspot activity, a
      proxy for total solar irradiance (particularly UV-R) reaching Earth, and the
      occurrence of folate-sensitive, epigenomic-related neonatal genotypes during the
      first trimester of pregnancy. Limited data is provided to support the hypothesis
      that the solar cycle predicts folate-related human embryo loss: 379 neonates born
      at latitude 54 degrees N between 1998 and 2000 were examined for three folate
      sensitive, epigenome-related polymorphisms, with solar activity for trimester one
      accessed via the Royal Greenwich Observatory-US Air force/National Oceanic and
      Atmospheric Administration Sunspot Database (34,110 total observation days).
      Logistic regression showed solar activity predicts C677T
      methylenetetrahydrofolate reductase (C677T-MTHFR) and A66G-methionine synthase
      reductase (A66G-MSR) genotype at discrete phases of trimester one. Total and
      maximal sunspot activity predicts C677T-MTHFR genotype for days 31-60 of
      trimester one (p=0.0181 and 0.0366, respectively) and A66G-MSR genotype for days
      61-90 of trimester one (p=0.0072 and 0.0105, respectively). Loss of UV-R
      sensitive folate associated with the sunspot cycle might therefore interact with
      variant folate genes to perturb DNA methylation and/or elaboration of the primary
      base sequence (thymidylate synthesis), as well as increase embryo-toxic
      homocysteine. We hypothesise that this may influence embryo viability leading to
      677CC-MTHFR and 66GG-MSR embryo loss at times of increased solar activity. This
      provides an interesting and plausible link between well recognised 'folate gene
      originated developmental disorders' and 'solar activity/seasonality modulated
      developmental disorders'.

PMID- 22608859
TI  - Integrating repopulation and regeneration of the auxiliarily transplanted small
      liver graft: the solution for organ shortage and immunosuppression.
AB  - Cirrhosis is a common yet generally irreversible medical condition which would
      cause damaged liver function and regeneration after resection. When the disease
      progressed to end stage, liver transplantation, cadaveric or live donor, would be
      the only way to eliminate the disease. But both have their confinements, such as
      organ shortage, detriments to the donors, and immunosuppression. Now that the
      techniques of auxiliary transplantation are in practice, and the phenomenon of
      graft repopulated by cells of host origin has been observed, and that elevated
      blood inflow would stimulate the regenerative response, the combination of the
      three might give rise to a non-immunogeneic customized liver. We hypotheses that
      it can be achieved through a auxiliary transplantation of a extremely small but
      normal graft combined with progressive portal control on the portal inflow of the
      native liver to induce atrophy of the cirrhotic liver and the regeneration of the
      graft, as well as postoperative administration of bone marrow mobilizing agents
      and reduced administration of immunosuppressants to initiate repopulation. This
      will not only solve the issue of organ shortage as one organ can be shared by
      more, and in case of live donor, less detriments would occur due to reduced size
      needed; but diminish, even eliminate the adverse effect caused by
      immunosuppression as well.

PMID- 22608860
TI  - Are uterine leiomyoma a consequence of a chronically inflammatory immune system?
AB  - The cumulative incidence of uterine leiomyoma at age 50 is ~ 70% in White women
      and >80% in Black women. Although risk factor research is limited, increasing
      age, and being premenopausal, nulliparous or Black are risk factors for
      leiomyomas. Black women tend to have larger leiomyomas and be younger at
      diagnosis. Surprisingly little is known about the etiology or pathogenesis of
      uterine leiomyomas. Women with diagnosed uterine leiomyomas have higher
      healthcare costs - more than 2.5 times that of women without a diagnosis. In the
      United States, leiomyomas are the leading indication for hysterectomy. The
      proposed hypothesis is that leiomyomas are caused in part by a systemic immune
      milieu that is chronically inflammatory - one that predominates in T helper 17
      (Th17) cytokines. Inflammation can be problematic if it is not well regulated.
      Should an inflammatory imbalance be demonstrated to be associated with leiomyoma
      development and growth, this would provide an avenue for development of
      preventative treatments (e.g., focus on anti-inflammatory pathways), which would
      substantially reduce the morbidity costs of these tumors and reduce a known
      health disparity.

PMID- 22608861
TI  - Cardiac MRI assessment of right ventricular function in acquired heart disease:
      factors of variability.
AB  - RATIONALE AND OBJECTIVES: To evaluate intra- and inter-observer variability of
      right ventricular (RV) functional parameters as evaluated by cardiac magnetic
      resonance imaging (MRI) in patients with acquired heart disease (AHD), and to
      identify factors associated with an increased variability. MATERIALS AND METHODS:
      Sixty consecutive patients were enrolled. Right and left ventricular (LV)
      volumes, ejection fraction, and mass were determined from short-axis cine
      sequences. All analyzes were performed twice by three observers with various
      training-degree in cardiac MRI. Intra- and inter-observer variability was
      evaluated. The impact on variability of each of the following parameters was
      assessed: observer's experience, basal and apical slices selection, end-systolic
      phase selection, and delineation. RESULTS: Mean segmentation time ranged 9.8-19.0
      minutes for RV and 6.4-9.2 minutes for LV. Variability of RV functional
      parameters measurement was strongly influenced by previous observer's experience:
      it was two to three times superior to that of LV, even for the most experienced
      observer. High variability in the measurement of RV mass was observed. For both
      ventricles, selection of the basal slice and delineation were major determinants
      of variability. CONCLUSION: As compared to LV, RV function assessment with
      cardiac MRI in AHD patients is much more variable and time-consuming. Observer's
      experience, selection of basal slice, and delineation are determinant.

PMID- 22608862
TI  - Perfusion-weighted MR imaging in cerebral lupus erythematosus.
AB  - RATIONALE AND OBJECTIVE: Neuropsychiatric systemic lupus erythematosus (NPSLE) is
      a diagnostically challenging, severe, and life-threatening condition, which is
      currently lacking a "gold standard." Our aim with this study is to look for
      magnetic resonance (MR) perfusion differences in NPSLE, SLE, and healthy control
      (HC) patients and correlate our findings with clinical parameters. MATERIALS AND
      METHODS: Twenty-four NPSLE patients, 21 SLE patients, and 21 HC underwent dynamic
      susceptibility contrast enhanced MR perfusion using a 3-T scanner. Nine
      prospectively selected intracranial regions of interest were placed in white and
      gray matter and the cerebral blood flow (CBF), cerebral blood volume (CBV), and
      mean transit time (MTT) values were calculated. Subjects underwent clinical
      evaluation with SLEDAI and serum antibodies. RESULTS: The SLE patients had higher
      CBF and CBV compared to the HC overall (P = .01) and in specific areas (P = .03
      .048). SLE patients with signs of active disease (elevated SLEDAI and anti-double
      stranded DNA) had significantly elevated CBV, CBF, and MTT in the posterior
      cingulate gyrus (P = .01-.02). No significant difference was seen in the magnetic
      resonance perfusion measurements of NPSLE patients compared to SLE and HC,
      although the NPSLE patients also showed higher CBV variability compared to the
      SLE (P = .0004) and HC cohort (P < .0001). CONCLUSION: SLE patients have
      increased CBV and CBF compared to healthy controls. The SLE patients with
      clinical markers for active disease have elevated CBV, CBF, and MTT in the
      posterior cingulate gyrus. NPSLE patients show increased variability in perfusion
      measurements, which may explain why susceptibility contrast enhanced MRI has not
      yet provided a specific target for NPSLE.

PMID- 22608864
TI  - Value-based reengineering: twenty-first century chronic care models.
AB  - The need for improved models of chronic care is great and will become critical
      over the next years as the Medicare-aged population doubles. Many promising
      models have been developed by outstanding groups across the country. This article
      reviews key strategies used by successful models in chronic disease management
      and discusses in detail how Geisinger has evolved and organized its cohesive
      delivery model.

PMID- 22608863
TI  - Urban-rural disparities of child health and nutritional status in China from 1989
      to 2006.
AB  - This paper analyzes urban-rural disparities of China's child health and
      nutritional status using the China Health and Nutrition Survey data from 1989 to
      2006. We investigate degrees of health and nutritional disparities between urban
      and rural children in China as well as how such disparities have changed during
      the period 1989-2006. The results show that on average urban children have 0.29
      higher height-for-age z-scores and 0.19 greater weight-for-age z-scores than
      rural children. Urban children are approximately 40% less likely to be stunted
      (OR=0.62; p<0.01) or underweight (OR=0.62; p<0.05) during the period 1989-2006.
      We also find that the urban-rural health and nutritional disparities have been
      declining significantly from 1989 to 2006. Both urban and rural children have
      increased consumption of high protein and fat foods from 1989 to 2006, but the
      urban-rural difference decreased over time. Moreover, the urban-rural gap in
      child preventive health care access was also reduced during this period.

PMID- 22608866
TI  - A "how to" guide to creating a patient-centered medical home.
AB  - The concept of the patient-centered medical home (PCMH) has been widely embraced
      as a foundation for the transformation of health care delivery. Recent
      evaluations of PCMH pilots validate the initial hypothesis that care provided in
      the PCMH has the potential to result in better health outcomes at lower cost.
      However, earning recognition or certification as a PCMH can be a daunting task.
      This article discusses the process of developing the potential to function as a
      PCMH, earning formal recognition, and implementing a system of continuous quality
      improvement to enable the establishment of a mature, sustainable PCMH.

PMID- 22608865
TI  - The changes involved in patient-centered medical home transformation.
AB  - In 2007, the major primary care professional societies collaboratively introduced
      a new model of primary care: the patient-centered medical home (PCMH). The
      published document outlines the basic attributes and expectations of a PCMH but
      not with the specificity needed to help interested clinicians and administrators
      make the necessary changes to their practice. To identify the specific changes
      required to become a medical home, the authors reviewed literature and sought the
      opinions of two multi-stakeholder groups. This article describes the eight
      consensus change concepts and 32 key changes that emerged from this process, and
      the evidence supporting their inclusion.

PMID- 22608867
TI  - Effective strategies for behavior change.
AB  - Strategies that are most effective in both prevention and management of chronic
      disease consider factors such as age, ethnicity, community, and technology. Most
      behavioral change strategies derive their components from application of the
      health belief model, the theory of reasoned action/theory of planned behavior,
      transtheoretical model, and social cognitive theory. Many tools such as the
      readiness ruler and personalized action plan form are available to assist health
      care teams to facilitate healthy behavior change. Primary care providers can
      support behavior changes by providing venues for peer interventions and family
      meetings and by making new partnerships with community organizations.

PMID- 22608868
TI  - Self-management education and support in chronic disease management.
AB  - With the changing health care environment, prevalence of chronic health
      conditions, and burgeoning challenges of health literacy, obesity, and
      homelessness, self-management support provides an opportunity for clinicians to
      enhance effectiveness and, at the same time, to engage patients to participate in
      managing their own personal care. This article reviews the differences between
      patient education and self-management and describes easy-to-use strategies that
      foster patient self-management and can be used by health care providers in the
      medical setting. It also highlights the importance of linking patients to
      nonmedical programs and services in the community.

PMID- 22608869
TI  - Health information technology: transforming chronic disease management and care
      transitions.
AB  - Adoption of health information technology (HIT) is a key effort in improving care
      delivery, reducing costs of health care, and improving the quality of health
      care. Evidence from electronic health record (EHR) use suggests that HIT will
      play a significant role in transforming primary care practices and chronic
      disease management. This article shows that EHRs and HIT can be used effectively
      to manage chronic diseases, that HIT can facilitate communication and reduce
      efforts related to transitions in care, and that HIT can improve patient safety
      by increasing the information available to providers and patients, improving
      disease management and safety.

PMID- 22608870
TI  - Pharmacologic issues in management of chronic disease.
AB  - A significant portion of the adult population uses one or more medications on a
      regular basis to manage chronic conditions. As the number of medications that
      patients are prescribed increases, an increase in pharmacologic-related issues
      and complications may occur, such as polypharmacy, inappropriate prescribing,
      medication nonadherence and nonpersistence, and adverse drug reactions and
      events. Risk factors and consequences of these issues have been identified and
      are discussed in this article. In addition, a review is presented of the numerous
      methods that have been evaluated to help prevent and minimize these pharmacologic
      issues in the management of chronic disease.

PMID- 22608871
TI  - Effective strategies to improve the management of diabetes: case illustration
      from the diabetes health and wellness institute.
AB  - Many patients with diabetes do not have access to clinical care or medications,
      resulting in cases of undiagnosed diabetes or uncontrolled diabetes, especially
      in patients of low socioeconomic status. Given these considerations, new
      strategies are needed to control the rampant growth of diabetes and prevent new
      cases. This article discusses effective strategies for improving the management
      of diabetes in underserved populations, with special reference to the Juanita J.
      Craft Diabetes Health and Wellness Institute, a unique partnership between a
      large, urban integrated health care system, the City of Dallas, and a South
      Dallas community.

PMID- 22608872
TI  - Childhood asthma: considerations for primary care practice and chronic disease
      management in the village of care.
AB  - Childhood asthma is at historically high levels, with significant morbidity and
      mortality. Despite more than two decades of improved understanding of childhood
      asthma care and the evolution of beneficial medications, widespread control
      remains poor, leading to suboptimal patient outcomes and quality of life. This
      lack of control results in excessive emergency department use, hospitalizations,
      and inappropriate and/or unnecessary costs to the health care system. Advanced
      practice models that incorporate community-based approaches and services for
      childhood asthma are needed. Innovative, community-included methods of care to
      address the burden of childhood asthma may provide examples for care of other
      chronic diseases.

PMID- 22608873
TI  - Effective strategies to improve the management of heart failure.
AB  - The purpose of this article is to provide resources for primary care physicians
      to manage heart failure as a chronic disease. We review evidence-based
      interventions that can be adopted in primary care practices to improve adherence
      to available guidelines for medication use, promotion of self-care behaviors,
      transitions of care in acute decompensated heart failure, and end of life care.
      This information will be valuable to primary care providers who care for patients
      with heart failure in all care settings but is focused on the management of heart
      failure in the outpatient setting.

PMID- 22608875
TI  - Community-based partnerships for improving chronic disease management.
AB  - With the growing burden of chronic disease, the medical and public health
      communities are re-examining their roles and opportunities for more effective
      prevention and clinical interventions. The potential to significantly improve
      chronic disease prevention and have an impact on morbidity and mortality from
      chronic conditions is enhanced by adopting strategies that incorporate a social
      ecology perspective, realigning the patient-physician relationship, integrating
      population health perspectives into the Chronic Care Model, and effectively
      engaging communities using established principles of community engagement.

PMID- 22608874
TI  - Strategies to improve the management of depression in primary care.
AB  - Effective management of depression in the primary care setting requires a
      systematic, population-based approach, which entails systematic case finding and
      diagnosis, patient engagement and education, use of evidence-based treatments,
      including medications and/or psychotherapy, close follow-up to ensure patients
      are improving, and a commitment to adjust treatments or consult with mental
      health specialists until depression is significantly improved. Programs in which
      primary care providers and mental health specialists collaborate effectively
      using principles of measurement-based stepped care and treatment to target can
      substantially improve patients' health and functioning while reducing overall
      health care costs.

PMID- 22608876
TI  - Teaching strategies behind the principles.

PMID- 22608877
TI  - Chronic disease management: the changing landscape of primary care.

PMID- 22608878
TI  - Satisfaction with nurse-led telephone follow up for low to intermediate risk
      prostate cancer patients treated with radical radiotherapy. A comparative study.
AB  - PURPOSE OF THE RESEARCH: As the number of men living with prostate cancer is
      increasing worldwide, the requirement for follow up care also grows. This study
      was undertaken to evaluate nurse-led, telephone follow up, for men with low to
      intermediate risk prostate cancer treated with radical radiotherapy when compared
      with medical follow up. METHODS AND SAMPLE: A non-randomized, two-cohort,
      comparative study. 169 men diagnosed with prostate cancer were recruited from
      outpatient clinics at a tertiary cancer centre in Australia. 83 men were
      recruited to cohort 1 (control) (51 low to intermediate risk; 32 high risk) and
      86 to cohort 2 (intervention) (51 low to intermediate risk; 35 high risk). High
      risk patients, regardless of cohort, received medical follow up. Low to
      intermediate risk patients in cohort 2 were triaged to nurse-led review for their
      six month review appointment. Nurse-led follow up consisted of six monthly
      telephone consultations and PSA testing. MEASURES: Participants completed the
      Satisfaction with Consultation Scale, the Brief Distress Thermometer and the
      Expanded Prostate Cancer Index Composite. KEY RESULTS: There was no statistically
      significant difference in patient satisfaction on any of the study measures
      between the nurse-led and standard medical follow up at six months following
      treatment completion. However, where there was a trend towards significance
      (p=0.051), it favoured the nurse-led follow up regimen. CONCLUSIONS: Nurse-led
      telephone consultation provides an acceptable model of follow-up for men
      diagnosed with low to intermediate risk prostate cancer. Multi-centre randomised
      controlled trials are needed to support the efficacy of nurse-led, telephone
      follow up services.

PMID- 22608879
TI  - In vitro supplementation with deoxynucleoside monophosphates rescues
      mitochondrial DNA depletion.
AB  - Mitochondrial DNA depletion syndromes are a genetically heterogeneous group of
      often severe diseases, characterized by reduced cellular mitochondrial DNA
      content. Investigation of potential therapeutic strategies for mitochondrial DNA
      depletion syndromes will be dependent on good model systems. We have previously
      suggested that myotubes may be the optimal model system for such studies. Here we
      firstly validate this technique in a diverse range of cells of patients with
      mitochondrial DNA depletion syndromes, showing contrasting effects in cell lines
      from genetically and phenotypically differing patients. Secondly, we developed a
      putative therapeutic approach using variable combinations of deoxynucleoside
      monophosphates in different types of mitochondrial DNA depletion syndromes,
      showing near normalization of mitochondrial DNA content in many cases.
      Furthermore, we used nucleoside reverse transcriptase inhibitors to precisely
      titrate mtDNA depletion in vitro. In this manner we can unmask a physiological
      defect in mitochondrial depletion syndrome cell lines which is also ameliorated
      by deoxynucleoside monophosphate supplementation. Finally, we have extended this
      model to study fibroblasts after myogenic transdifferentiation by MyoD
      transfection, which similar to primary myotubes also showed deoxynucleoside
      monophosphate responsive mitochondrial DNA depletion in vitro, thus providing a
      more convenient method for deriving future models of mitochondrial DNA depletion.
      Our results suggest that using different combinations of deoxynucleoside
      monophosphates depending on the primary gene defect and molecular mechanism may
      be a possible therapeutic approach for many patients with mitochondrial DNA
      depletion syndromes and is worthy of further clinical investigation.

PMID- 22608880
TI  - Allelic variations in superoxide dismutase-1 (SOD1) gene and renal and
      cardiovascular morbidity and mortality in type 2 diabetic subjects.
AB  - BACKGROUND: Oxidative stress is involved in the pathophysiology of renal and
      cardiovascular complications of diabetes. Superoxide dismutase (SOD) enzymes play
      a major role in detoxification of reactive oxygen species and protection against
      oxidative stress. Associations of SOD1 gene variants with diabetic nephropathy
      were reported in patients with type 1 diabetes. We investigated associations of
      allelic variations in SOD1 gene with nephropathy and cardiovascular complications
      in patients with type 2 diabetes. METHODS: Seven SNPs in SOD1 region were
      analyzed in 3744 type 2 European Caucasian diabetic patients from the DIABHYCAR
      (a 6-year prospective study) and DIABHYCAR_GENE cohorts. Odds ratios or hazard
      ratios for prevalence and incidence of diabetic nephropathy and cardiovascular
      events were estimated. RESULTS: We observed an association of rs1041740 with the
      prevalence of microalbuminuria at baseline (OR 1.51, 95% CI 1.10-2.10, p=0.01).
      No association with the incidence of renal events (doubling of the serum
      creatinine levels or the requirement of hemodialysis or renal transplantation) or
      cardiovascular events (myocardial infarction or stroke) was observed during
      follow-up. However, three variants were associated with increased risk of death
      from cardiovascular causes (sudden death, fatal myocardial infarction or stroke)
      during the follow-up: rs9974610 (HR 0.64, 95% CI 0.46-0.88, p=0.005), rs10432782
      (HR 1.71, 95% CI 1.16-2.48, p=0.007) and rs1041740 (HR 1.78, 95% CI 1.10-2.78,
      p=0.02). CONCLUSIONS: Our results are consistent with a major role for SOD1 in
      the mechanisms of cardiovascular protection against oxidative stress in type 2
      diabetic subjects.

PMID- 22608881
TI  - Single nucleotide polymorphisms in sFRP4 are associated with bone and body
      composition related parameters in Danish but not in Belgian men.
AB  - The senescence accelerated mouse P6 (SAMP6) has a low bone mass and has
      previously shown to be a good model for senile osteoporosis in humans. In
      addition to a reduced bone mass, SAMP6 mice are obese and have hyperlipidemia.
      Using positional cloning and expression studies, an increased expression of sfrp4
      was found in these mice. SFRP4 is a modulator of the Wnt signalling pathway. This
      pathway has been previously shown to be involved in regulating bone mass.
      Additional evidence that sFRP4 has an influence on BMD was delivered by linkage
      and association studies mostly performed in Asian populations. Based on these
      data we decided to perform an association study between common variants in sFRP4,
      BMD, hip geometry parameters and body composition parameters in a population
      consisting of 1383 Danish men (783 aged 20-29 years; 600 aged 60-74 years).
      Afterwards we tried to replicate the significant results in a population of 994
      Belgian men. In the Danish population we found 6 SNPs associated with BMD at the
      hip and/or femoral neck. Furthermore, all 6 SNPs were associated with several hip
      geometry parameters. The homozygous presence of the minor allele resulted for all
      SNPs (except rs4720265) in a decrease in bone density and bone strength. Finally,
      we observed in the Danish population age specific associations with height and
      fat mass. In the Belgian population we tried to replicate the results of three
      SNPs with BMD and body composition parameters. Unfortunately, we were not able to
      replicate the results found in the Danish cohort but we found one SNP (rs2598116)
      associated with height. In conclusion, genetic variation in sFRP4 has an
      influence on hip fracture risk, percentage body fat and height in a Danish male
      population. However, we were unable to replicate these results in an independent
      Belgian population.

PMID- 22608882
TI  - McArdle disease: a novel mutation in Jewish families from the Caucasus region.
AB  - McArdle disease is caused by a myophosphorylase deficiency consequent to defects
      in the PYGM gene. A minority of the over-133 known mutations are associated with
      ethnicity, occurring mainly in patients from western Europe, the United States,
      and Japan. We identified a novel mutation, c.632delG, in three unrelated families
      of Jewish descent originating from the Caucasus region. This possibly ethnicity
      associated mutation can significantly facilitate the diagnosis in Jews of the
      Caucasus and contribute to genetic consultations.

PMID- 22608883
TI  - Effects of interferon-beta therapy on elements in the antiviral immune response
      towards the human herpesviruses EBV, HSV, and VZV, and to the human endogenous
      retroviruses HERV-H and HERV-W in multiple sclerosis.
AB  - Effects of treatment of multiple sclerosis patients with IFN-beta on elements of
      the antiviral immune response to herpesviruses were analysed in a longitudinal
      study. We found significantly increased seroreactivity to EBV EBNA-1, and to VZV,
      in patients who did not respond to IFN-beta therapy. We found no significant
      changes in seroreactivity to EBV EA, or to HSV. For the same patient cohort, we
      have previously demonstrated significant decreases in seroreactivities to
      envelope antigens for the two human endogenous retroviruses HERV-H and HERV-W,
      closely linked to efficacy of therapy. We further searched for correlations
      between seroreactivities to EBV, HSV, and VZV, and levels of mannan-binding
      lectin (MBL), and MBL-associated serine protease 3. We found no such
      correlations. Our results are in accord with recent reports of increased
      seroreactivity to EBV EBNA-1, and to VZV in active MS, and they support that the
      herpesviruses EBV and VZV together with HERV-H/HERV-W and the antiviral immune
      response may play a role in MS development.

PMID- 22608884
TI  - Altered frequency of T regulatory cells is associated with disability status in
      relapsing-remitting multiple sclerosis patients.
AB  - A perturbed immunoregulation may be part of the pathogenesis of relapsing
      remitting multiple sclerosis (RRMS). In this study, we demonstrate a dichotomy
      within the frequency of Treg among newly diagnosed RRMS patients but not in
      healthy controls. A group of RRMS patients was characterized by a significantly
      lower percentage of Treg cells than that of their matched, healthy controls, and
      this was inversely correlated with their score on the expanded disability status
      scale (EDSS). Since the EDSS reflected severity of the last attack, this study
      demonstrates a correlation between low frequency of Treg and severity of clinical
      disease in RRMS.

PMID- 22608885
TI  - A novel long-range PCR sequencing method for genetic analysis of the entire PKD1
      gene.
AB  - Genetic testing of PKD1 and PKD2 is useful for the diagnosis and prognosis of
      autosomal dominant polycystic kidney disease; however, analysis is complicated by
      the large transcript size, the complexity of the gene region, and the high level
      of gene variations. We developed a novel mutation screening assay for PKD1 by
      directly sequencing long-range (LR) PCR products. By using this method, the
      entire PKD1 coding region was amplified by nine reactions, generating product
      sizes from 2 to 6 kb, circumventing the need for specific PCR amplification of
      individual exons. This method was compared with direct sequencing used by a
      reference laboratory and the SURVEYOR-WAVE Nucleic Acid High Sensitivity Fragment
      Analysis System (Transgenomic) screening method for five patients with autosomal
      dominant polycystic kidney disease. A total of 53 heterozygous genetic changes
      were identified by LR PCR sequencing, including 41 (of 42) variations detected by
      SURVEYOR nuclease and all 32 variations reported by the reference laboratory,
      detecting an additional 12 intronic changes not identified by the other two
      methods. Compared with the reference laboratory, LR PCR sequencing had a
      sensitivity of 100%, a specificity of 98.5%, and an accuracy of 98.8%; compared
      with the SURVEYOR-WAVE method, it had a sensitivity of 97.1%, a specificity of
      100%, and an accuracy of 99.4%. In conclusion, LR PCR sequencing was superior to
      the direct sequencing and screening methods for detecting genetic variations,
      achieving high sensitivity and improved intronic coverage with a faster
      turnaround time and lower costs, and providing a reliable tool for complex
      genetic analyses.

PMID- 22608886
TI  - Potential of hybrid computational phantoms for retrospective heart dosimetry
      after breast radiation therapy: a feasibility study.
AB  - PURPOSE: Current retrospective cardiovascular dosimetry studies are based on a
      representative patient or simple mathematic phantoms. Here, a process of patient
      modeling was developed to personalize the anatomy of the thorax and to include a
      heart model with coronary arteries. METHODS AND MATERIALS: The patient models
      were hybrid computational phantoms (HCPs) with an inserted detailed heart model.
      A computed tomography (CT) acquisition (pseudo-CT) was derived from HCP and
      imported into a treatment planning system where treatment conditions were
      reproduced. Six current patients were selected: 3 were modeled from their CT
      images (A patients) and the others were modelled from 2 orthogonal radiographs (B
      patients). The method performance and limitation were investigated by
      quantitative comparison between the initial CT and the pseudo-CT, namely, the
      morphology and the dose calculation were compared. For the B patients, a
      comparison with 2 kinds of representative patients was also conducted. Finally,
      dose assessment was focused on the whole coronary artery tree and the left
      anterior descending coronary. RESULTS: When 3-dimensional anatomic information
      was available, the dose calculations performed on the initial CT and the pseudo
      CT were in good agreement. For the B patients, comparison of doses derived from
      HCP and representative patients showed that the HCP doses were either better or
      equivalent. In the left breast radiation therapy context and for the studied
      cases, coronary mean doses were at least 5-fold higher than heart mean doses.
      CONCLUSIONS: For retrospective dose studies, it is suggested that HCP offers a
      better surrogate, in terms of dose accuracy, than representative patients. The
      use of a detailed heart model eliminates the problem of identifying the
      coronaries on the patient's CT.

PMID- 22608887
TI  - Functional outcome after arthroscopic repair of massive rotator cuff tears in
      individuals with pseudoparalysis.
AB  - PURPOSE: The purpose of this study was to evaluate the functional results after
      arthroscopic rotator cuff repair (ARCR) for patients with preoperative
      pseudoparalysis. METHODS: This retrospective review examined massive rotator cuff
      tears treated with an ARCR over a 10-year period. Pseudoparalysis was defined as
      active forward flexion (FF) less than or equal to 90 degrees  with full passive
      FF. Primary ARCRs (group I) and revision ARCRs (group II) were included.
      Postoperative reversal of pseudoparalysis, functional outcome, and complications
      were self-assessed at a minimum of 2 years postoperatively. RESULTS: In group I
      39 patients with a mean age of 62 years at the time of surgery were available for
      follow-up at a mean of 75 months. Active FF improved from 49 degrees 
      preoperatively to 155 degrees  postoperatively (P < .001), and pseudoparalysis
      was reversed in 90% of patients. In group II 14 patients with a mean age of 63
      years at the time of surgery were available for follow-up at a mean of 72 months.
      Active FF improved from 43 degrees  to 109 degrees  (P < .001), and
      pseudoparalysis was reversed in 43% of patients. The mean American Shoulder and
      Elbow Surgeons score improved in both group I (P < .001) and group II (P = .033).
      Recovery of FF greater than 90 degrees  in group I was associated with a shorter
      interval before repair (P = .021) and a complete repair (P = .026). CONCLUSIONS:
      ARCR of massive rotator cuff tears with advanced mobilization techniques can lead
      to reversal of preoperative pseudoparalysis in 90% of patients who have not had
      previous surgery. In these patients functional improvement can be obtained with a
      low rate of complications. However, in the setting of a revision ARCR and
      pseudoparalysis, only 43% of patients regained FF above 90 degrees . LEVEL OF
      EVIDENCE: Level IV, therapeutic case series.

PMID- 22608888
TI  - Long-term results after SLAP repair: a 5-year follow-up study of 107 patients
      with comparison of patients aged over and under 40 years.
AB  - PURPOSE: The aims of this prospective cohort study were to assess the long-term
      results after isolated superior labral repair and to determine whether the
      results were associated with age. METHODS: One hundred seven patients underwent
      repair of isolated SLAP tears. There were 36 women and 71 men with a mean age of
      43.8 years (range, 20 to 68 years). Mean follow-up was 5.3 years (range, 4 to 8
      years). Of the patients, 62 (57.9%) were aged 40 years or older. Follow-up
      examinations were performed by an independent examiner; 102 patients (95.3%) had
      a 5-year follow-up. RESULTS: The Rowe score improved from 62.8 (SD, 11.4)
      preoperatively to 92.1 (SD, 13.5) at follow-up (P < .001). Satisfaction was rated
      excellent/good for 90 patients (88%) at 5 years. There was no significant
      difference in the results for patients aged 40 years or older and those aged
      under 40 years. Difficulty with postoperative stiffness and pain was reported by
      14 patients (13.1%). CONCLUSIONS: Our results suggest that long-term outcomes
      after isolated labral repair for SLAP lesions are good and independent of age.
      Postoperative stiffness was registered in 13.1% of the patients. LEVEL OF
      EVIDENCE: Level IV, therapeutic case series.

PMID- 22608889
TI  - A comparison of glenoid morphology and glenohumeral range of motion between
      professional baseball pitchers with and without a history of SLAP repair.
AB  - PURPOSE: We sought to examine the relation among glenoid morphology, glenohumeral
      range of motion (ROM), and history of shoulder injury in professional baseball
      pitchers. METHODS: We studied 58 professional baseball pitchers. Internal
      rotation (IR) and external rotation (ER) ROM was measured at 90 degrees  of
      abduction. Horizontal adduction (HAdd) ROM was also measured. Glenoid superior
      inclination and glenoid retroversion (GRV) were then measured radiographically.
      Separate mixed-model analyses of variance were used to compare dependent measures
      between the dominant and nondominant shoulders of pitchers with or without a
      history of SLAP repair. Significant interaction effects were interpreted by use
      of a test for simple main effects (alpha = .05). RESULTS: GRV was significantly
      greater on the dominant side (8.7 degrees  +/- 5.6 degrees ) versus nondominant
      side (5.5 degrees  +/- 5.2 degrees ) (P = .001), whereas glenoid superior
      inclination was equivalent (99.5 degrees  +/- 4.3 degrees  for dominant side v
      99.2 degrees  +/- 4.4 degrees  for nondominant side, P = .853). Post hoc analysis
      indicated that pitchers with a history of SLAP repair did not display an adaptive
      increase in dominant GRV compared with nondominant GRV (P = .016). There were no
      statistical differences between groups for ER (P = .29), IR (P = .39), or HAdd (P
      = .39). The dominant shoulder displayed greater ER (mean increase, 6.2 degrees 
      +/- 12.2 degrees ) with a complementary decrease in IR (mean decrease, 5.8
      degrees  +/- 13.2 degrees ) and HAdd (mean decrease, 8.9 degrees  +/- 13.7
      degrees ) compared with the nondominant side. CONCLUSIONS: Our findings suggest
      that the development of increased GRV in the dominant shoulder of professional
      baseball pitchers may be a protective adaptive change not reflected in
      glenohumeral ROM measures. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 22608890
TI  - High incidence of athletic pubalgia symptoms in professional athletes with
      symptomatic femoroacetabular impingement.
AB  - PURPOSE: The purpose of this study was to identify the incidence of symptoms
      consistent with athletic pubalgia (AP) in athletes requiring surgical treatment
      for femoroacetabular impingement (FAI) and the frequency of surgical treatment of
      both AP and FAI in this group of patients. METHODS: Thirty-eight consecutive
      professional athletes, with a mean age of 31 years, underwent arthroscopic
      surgery for symptomatic FAI that limited their ability to play competitively. In
      all cases a cam and/or focal rim osteoplasty with labral refixation or
      debridement was performed. In 1 case concomitant intramuscular lengthening of the
      psoas was performed. Retrospective data regarding prior AP surgery and return to
      play were collected. RESULTS: Thirty-two percent of patients had previously
      undergone AP surgery, and 1 patient underwent AP surgery concomitantly with
      surgical treatment of FAI. No patient returned to his previous level of
      competition after isolated AP surgery. Thirty-nine percent had AP symptoms that
      resolved with FAI surgery alone. Of the 38 patients, 36 returned to their
      previous level of play; all 12 patients with combined AP and FAI surgery returned
      to professional competition. The mean duration before return to play was 5.9
      months (range, 3 to 9 months) after arthroscopic surgery. CONCLUSIONS: There is a
      high incidence of symptoms of AP in professional athletes with FAI of the hip.
      This study draws attention to the overlap of these 2 diagnoses and highlights the
      importance of exercising caution in diagnosing AP in a patient with FAI. LEVEL OF
      EVIDENCE: Level IV, therapeutic, retrospective case series.

PMID- 22608891
TI  - Efficiency of quantitative longitudinal peak systolic strain values using
      automated function imaging on transthoracic echocardiogram for evaluating left
      ventricular wall motion: new diagnostic criteria and agreement with naked eye
      evaluation by experienced cardiologist.
AB  - PURPOSE: To evaluate the efficiency of automated function imaging (AFI) on
      transthoracic echocardiogram (TTE) for detecting left ventricular (LV) wall
      motion (LVWM) abnormalities, we compared longitudinal peak systolic strain (LPSS)
      measurements using AFI with naked eye TTE evaluations by experienced
      cardiologists and non-experienced residents. MATERIALS AND METHODS: A total of
      352 segments of LV myocardium from 22 consecutive subjects with LVWM
      abnormalities based on American Heart Association classifications (11 male, mean
      age 58 +/- 14 years) on previous TTE (Vivid-7, GE) were evaluated. LPSS was
      measured using stored AFI data. Naked eye evaluation of LVWM was performed by 2
      experienced cardiologists and 2 non-experienced residents. RESULTS: AFI
      successfully tracked 342 (97%) of all segments (mean LPSS -14.8 +/- 8.1%). A
      significant strong negative correlation was observed between LV ejection fraction
      using method of disks and global LPSS (R=-0.8974). Temporary AFI criteria of LPSS
      were normal <-12; hypokinesis -12-2; and akinesis >2. Of 342 segments, 239, 87,
      and 16 segments were diagnosed as normal, hypokinesis, and akinesis,
      respectively. Level of agreement and kappa coefficients between qualitative
      evaluation of LVWM by AFI temporary criteria and qualitative evaluation of LVWM
      by experienced cardiologist 2 (0.784 and 0.479, respectively) were inferior to
      those comparing experienced cardiologists (0.845 and 0.595) but superior
      comparing experienced cardiologist with non-experienced resident (0.696 and
      0.323), and between the 2 non-experienced-residents (0.682 and 0.347).
      CONCLUSION: Qualitative evaluation of LVWM using temporary AFI criteria had a 97%
      success rate and agreed well with findings of an experienced cardiologist. AFI
      can be a useful tool for training residents.

PMID- 22608892
TI  - Intracoronary followed by intravenous administration of the short-acting beta
      blocker landiolol prevents myocardial injury in the face of elective percutaneous
      coronary intervention.
AB  - BACKGROUND: Myocardial injury during elective percutaneous coronary intervention
      (PCI) is associated with higher subsequent cardiac events and mortality. beta
      Blockers have been used to reduce myocardial injury during ischemia and
      reperfusion. We investigated whether intracoronary followed by intravenous
      administration of the short-acting beta-blocker landiolol prevents myocardial
      injury in the face of elective PCI. METHODS AND RESULTS: Patients undergoing
      elective PCI (n=70) were randomly assigned to the landiolol (n=35) or control
      (n=35) group. Landiolol or saline was administered into target vessels through a
      balloon catheter for 1min before and after first balloon inflation followed by
      continuous intravenous administration for 6h after PCI. The incidence of
      myocardial injury defined by cardiac troponin-I (cTnI) >/=0.05 ng/ml was 79% of
      the patients in the control group compared to 56% in the landiolol group
      (p=0.04). The cTnI level at 24h after PCI tended to be lower in the landiolol
      group (0.57 +/- 1.14 versus 1.27 +/- 2.48 ng/ml; p=0.07), while the CK-MB level
      was not significantly different between the landiolol and control groups. The
      incidence of peri-procedural myocardial infarction defined by cTnI >/=0.12 ng/ml
      was significantly (p=0.02) lower in the landiolol group (41%) compared to the
      control group (70%). There was no incidence of coronary spasm, hypotension,
      bradycardia or heart failure during and after PCI in the two groups. CONCLUSIONS:
      Brief intracoronary followed by continuous intravenous administration of
      landiolol is safe and effective for myocardial protection in the face of elective
      PCI.

PMID- 22608894
TI  - Stent implantation for stenotic Blalock-Taussig shunts in a 5.75-year-old boy
      with pulmonary atresia.

PMID- 22608893
TI  - Noninducibility after circumferential pulmonary vein isolation of paroxysmal
      atrial fibrillation improves clinical outcome: evidence from the Atrial
      Fibrillation Clinical Trial (AFCT) in China.

PMID- 22608896
TI  - The effect of exercise training on plasma NT-pro-BNP levels and its correlation
      with improved exercise ventilatory efficiency in patients with heart failure.

PMID- 22608895
TI  - Percutaneous device closure of atrial septal defect results in very early and
      sustained changes of right and left heart function.
AB  - OBJECTIVES: To investigate the echocardiographic effects of percutaneous closure
      of secundum atrial septal defect (ASD) in adults and assess which pre-closure
      parameters predict good response to closure. BACKGROUND: ASD is a common
      congenital heart disease often undiscovered until adulthood. ASD closure has been
      revolutionized by the use of percutaneous devices. The effects of these
      procedures on echocardiographic parameters are not well characterized. METHODS:
      Patients undergoing percutaneous device closure of ASD between June 2007 and June
      2009 had 3 sequential echocardiograms reviewed: pre-procedure, immediate post
      procedure (24 hours) and 6-8 weeks post-procedure. Significant changes from
      baseline were investigated using paired t-test/1-way ANOVA. Pearson correlation
      (2-tailed) tests were used to categorize patients as 'good responders' to closure
      in terms of selected parameters. RESULTS: 129 echocardiograms in 43 consecutive
      patients were included. Remodeling of both ventricles occurred immediately
      following ASD closure and was sustained. Right ventricular (RV) diameter in
      diastole decreased by 13.5% and 19.3% compared to baseline at 24 hours and 6-8
      weeks post-closure, respectively (p<0.05); Left ventricular (LV) diameter in
      diastole increased by 8.5% and 15.6%, respectively (p<0.05). Functional
      parameters of the RV also demonstrated early and sustained decreases (TAPSE
      decreased by 8.3% and 17% compared to baseline at 24 hours and 6-8 weeks post
      closure, respectively (p<0.05)). Smaller RV baseline diameter appeared to predict
      good response to closure. CONCLUSIONS: Percutaneous ASD closure has immediate,
      sustained benefits on multiple echocardiographic parameters. Good responders have
      smaller RV at baseline, suggesting early closure is preferable.

PMID- 22608897
TI  - Symptomatic but not asymptomatic non-sustained ventricular tachycardia is
      associated with appropriate implantable cardioverter therapy in tetralogy of
      Fallot.
AB  - BACKGROUND: A recently developed risk score model aims to predict appropriate
      implantable cardioverter defibrillator (ICD) therapy for primary prevention of
      sudden cardiac death in tetralogy of Fallot (TOF). We assessed the validity of
      the proposed risk score model. METHODS: Patients included in a retrospective
      international cohort were stratified according to the risk score system. Risk
      factors were prior shunt, inducible sustained ventricular tachycardia, QRS >= 180
      ms, ventriculotomy incision, nonsustained ventricular tachycardia (NSVT) and left
      ventricular end-diastolic pressure >= 12 mmHg (LVEDP). Left ventricular ejection
      fraction <= 35% measured by means of echocardiography was used because LVEDP
      values were incomplete in our cohort. RESULTS: Thirty-six adults had TOF and ICD
      for primary prevention (72% male, mean age 37 +/- 12). Seven patients (19%)
      received appropriate shocks during a median follow-up of 5.5 years. Of the
      proposed risk factors only NSVT was associated with appropriate shocks (HR 2.6,
      CI 1.1-6.0, P=0.02). Patients with asymptomatic NSVT did not receive any
      appropriate shocks. The 8-year Kaplan-Meier estimate from the first appropriate
      shock was 86%, 78% and 75% for low, intermediate and high risk patients,
      respectively. In this study, the annual rate of appropriate shocks was 4.1% in
      the high risk group which was considerably lower than that reported by Khairy and
      colleagues (17.5%). CONCLUSIONS: The risk score model of Khairy and colleagues
      was capable of identifying low versus intermediate/high risk patients. However,
      event rates of lethal arrhythmias were lower in our cohort than previously
      reported. Symptomatic but not asymptomatic NSVT was the sole clinical variable
      associated with appropriate ICD therapy in TOF.

PMID- 22608898
TI  - Time-to-treatment and infarct size in STEMI patients undergoing primary
      angioplasty.
AB  - BACKGROUND: Several reports have shown that in patient with ST-segment elevation
      acute myocardial infarction (STEMI) longer ischemia time is associated with
      impaired reperfusion and higher mortality. However, there is still some doubts
      with regards time to reperfusion role in patients treated with primary
      percutaneous coronary intervention (PCI). Therefore, the aim of the current study
      was to evaluate the impact of time-to-treatment on infarct size as evaluated by
      myocardial scintigraphy in a large cohort of STEMI patients undergoing primary
      PCI. METHODS: Our population is represented by 830 STEMI patients undergoing
      primary PCI. Infarct size was evaluated at 30 days by technetium-99m-sestamibi.
      RESULTS: Time-to-treatment was significantly associated with age and
      dyslipidemia. Time-to-treatment linearly affected the rate of postprocedural TIMI
      3 flow (p<0.0001) and scintigraphic infarct size (p<0.001). The impact of time-to
      treatment on infarct size persisted in the analysis restricted to patients with
      postpocedural TIMI 3 flow, and after correction for confounding factors such as
      age, dyslipidemia, postprocedural TIMI 3 flow (OR [95% CI]=1.26 [1.14-1.39],
      p<0.001). CONCLUSIONS: This study shows in a large population of STEMI patients
      undergoing primary PCI that time-to-treatment is linearly associated with infarct
      size.

PMID- 22608899
TI  - The patent ductus arteriosus controversy.

PMID- 22608901
TI  - Multiple brain abscesses in a neonate after blood stream infection with
      methicillin-resistant Staphylococcus aureus.

PMID- 22608903
TI  - Bilateral facial weakness.

PMID- 22608904
TI  - Importance of bladder bowel dysfunction in patients with urinary tract infection.

PMID- 22608905
TI  - White coat adherence over the first year of therapy in pediatric epilepsy.
AB  - OBJECTIVE: To examine white coat adherence over time in children with epilepsy.
      STUDY DESIGN: This was a longitudinal prospective study to examine medication
      adherence prior to and following consecutive clinic visits over a 13-month period
      in 120 children with newly diagnosed epilepsy (M(age) = 7.2 +/- 2.9 years; 38%
      female) and their caregivers. Electronic monitors were used to assess adherence
      and ordinal logistic regression models were employed. RESULTS: Results
      demonstrated white coat adherence, with adherence increasing during the 3 days
      preceding clinic visits. Data also revealed a significant interaction, whereby
      adherence increased following initial clinic visits, but decreased following the
      last clinic visit. CONCLUSIONS: White coat adherence occurs for children with
      newly diagnosed epilepsy. Increased awareness of white coat adherence has
      important implications for clinical decision-making and should be examined in
      other pediatric populations. Increased monitoring of medication patterns can help
      clinicians avoid unnecessary changes to the treatment regimen. Interventions
      targeting improved communication around adherence behaviors are necessary to
      maximize therapy benefits.

PMID- 22608906
TI  - An unusual thyroid mass in a 5-year-old girl.

PMID- 22608907
TI  - Obesity susceptibility loci on body mass index and weight loss in Spanish
      adolescents after a lifestyle intervention.
AB  - OBJECTIVE: To estimate the contribution of 9 obesity-related polymorphisms and a
      genetic predisposition score (GPS) on anthropometric and biochemical variables
      before and after a weight loss intervention program in overweight/obese Spanish
      adolescents. STUDY DESIGN: Overweight/obese adolescents (n = 168; 12-16 years)
      participating in the EVASYON program were genotyped for 9 obesity-related single
      nucleotide polymorphisms in the FTO, MC4R, TMEM18, IL6, PPARG, and ADIPQ genes.
      RESULTS: At baseline, the GPS showed a significant association with body mass
      index-standard deviation score (BMI-SDS) and fat mass. After 3 months of
      intervention, this GPS also showed a relationship with the variation of both
      anthropometric measurements. After adjusting for baseline BMI-SDS, subjects with
      a lower GPS had a greater improvement on metabolic profile, as well as a better
      response to physical activity, compared with those subjects with a higher GPS.
      CONCLUSIONS: The GPS seems to have an important relationship with BMI-SDS and fat
      mass both at baseline and after a 3-month weight loss lifestyle intervention.
      Obese and overweight adolescents with a lower GPS have a greater benefit of
      weight loss after 3 months of a multidisciplinary lifestyle intervention.

PMID- 22608909
TI  - Brugada syndrome unmasked by febrile illness in an asymptomatic child.

PMID- 22608910
TI  - Improving asthma care after an emergency visit: a universal challenge.

PMID- 22608911
TI  - A unique association with persistent truncus arteriosus and partial midline chest
      wall defect.

PMID- 22608912
TI  - [Erythematous-violaceous plaques on the limbs of a patient with rheumatoid
      arthritis and colon cancer].

PMID- 22608913
TI  - [Pacifier sucking habit and associated dental changes. Importance of early
      diagnosis].
AB  - INTRODUCTION: The non-nutritive sucking habits are a physiological activity
      during the first months of life of a child, but if they persist afterwards, these
      habits can affect the development of dental occlusion.The aim of this study was
      to determine the frequency of past pacifier-sucking habits in a sample of school
      children and its role in the genesis of dental malocclusion in primary dentition,
      as well as to follow up these alterations until the next phase of the dentition
      (mixed dentition). MATERIAL AND METHODS: We performed a longitudinal
      epidemiological study on a sample of 225 children from age 2 to 10 years in the
      Basque Autonomous Region.Data were obtained by means of a questionnaire of
      children habits, filled in by parents, and clinical tests carried out on the
      children, recording the presence of alterations in dental occlusion, such as
      anterior open bite and posterior crossbite. RESULTS: We found a significant
      increase of malocclusion in the primary dentition of children who prolonged the
      pacifier-sucking habit. If this habit was abandoned early, anterior open bites
      improved, while posterior crossbites clutch remained or even got worse.
      CONCLUSIONS: The pacifier sucking habit influences the development of the teeth,
      thus, it is necessary to detect early changes in order to prevent the
      establishment of dental malocclusion.

PMID- 22608914
TI  - Gamagrass varieties as potential feedstock for fermentable sugar production.
AB  - To evaluate the potential of gamagrass as a feedstock for biofuels, seven
      gamagrass varieties were analyzed for their chemical composition and subjected to
      pretreatment at 121  degrees C using 1% NaOH/H(2)SO(4) (w/w) for 60 min and
      enzymatic hydrolysis for fermentable sugar production. Based on total sugar
      yield, the varieties Eagle Point Devil Corn and Sun Devil were selected for NaOH
      and H(2)SO(4) pretreatment, respectively. The investigation on pretreatment
      conditions showed that, the conditions applied in gamagrass variety screening
      (121  degrees C, 1% NaOH/H(2)SO(4), 60 min) were sufficient to maximize sugar
      production, such that the total sugar yield of Eagle Point Devil Corn reached
      479.6 mg g(-1) after NaOH pretreatment and that of Sun Devil reached 456.5 mg g(
      1) raw biomass after H(2)SO(4) pretreatment. Compared with other potential energy
      crops including switchgrass and Bermuda grass, gamagrass gave a higher sugar
      yield after NaOH pretreatment and a comparable sugar yield after H(2)SO(4)
      pretreatment.

PMID- 22608915
TI  - Improved performance of the microbial electrolysis desalination and chemical
      production cell using the stack structure.
AB  - The microbial electrolysis desalination and chemical-production cell (MEDCC) is a
      device to desalinate seawater, and produce acid and alkali. The objective of this
      study was to enhance the desalination and chemical-production performance of the
      MEDCC using two types of stack structure. Experiments were conducted with
      different membrane spacings, numbers of desalination chambers and applied
      voltages. Results showed that the stack construction in the MEDCC enhanced the
      desalination and chemical-production rates. The maximal desalination rate of 0.58
      +/- 0.02 mmol/h, which was 43% higher than that in the MEDCC, was achieved in the
      four-desalination-chamber MEDCC with the AEM-CEM stack structure and the membrane
      spacing of 1.5mm. The maximal acid- and alkali-production rates of 0.079 +/-
      0.006 and 0.13 +/- 0.02 mmol/h, which were 46% and 8% higher than that in the
      MEDCC, respectively, were achieved in the two-desalination-chamber MEDCC with the
      BPM-AEM-CEM stack structure and the membrane spacing of 3mm.

PMID- 22608916
TI  - Matrix metalloproteinases in human sclerotic dentine of attrited molars.
AB  - OBJECTIVE: The relationship between the major proteinases in dentine matrix
      metalloproteinases (MMPs) and the formation of collagen-less sclerotic dentine is
      still unknown. This study is to compare the concentrations of dentinal MMP-1, -2,
      -3, -8, and -9 between human sound and sclerotic dentine. DESIGN: Eleven sound
      third molars from young patients and twenty-two attrited molars with sclerotic
      dentine from old patients were collected and three groups of dentine samples were
      obtained: sound dentine of young tooth (SDY), non-sclerotic dentine of attrited
      tooth (NDA) and sclerotic dentine of attrited tooth (SDA). The dentine powder
      from each group was subjected to demineralization and protein extraction in turn.
      Then the contents of MMP-1, -2, -3, -8 and -9 were quantitatively evaluated by
      Fluorescent Microsphere Immunoassay. The occlusal and fractured axial surfaces of
      sound and sclerotic dentine were observed using FEI-SEM. RESULTS: There was no
      significant difference in the concentration of MMP-1 amongst all tested groups
      (p>0.05). The contents of MMP -2 and MMP-3 in SDY were significantly higher than
      those in NDA and SDA (p<0.05). The contents of MMP -8 and MMP -9 in SDA were
      significantly higher than those in SDY and NDA (p<0.05). The surface
      hypermineralised layer and sclerotic casts were all detected in sclerotic dentine
      under SEM. CONCLUSIONS: The morphological characteristics of sclerotic dentine
      from the attrited molars were comparable to that from noncarious cervical
      lesions. Although depended on the type of MMP, the contents of dentinal MMPs
      changed during the formation of sclerotic dentine and long-term ageing.

PMID- 22608917
TI  - L-Carnitine: an adequate supplement for a multi-targeted anti-wasting therapy in
      cancer.
AB  - BACKGROUND & AIMS: Tumour growth is associated with weight loss resulting from
      both adipose and muscle wasting. METHODS: Administration of L-carnitine (1 g/kg
      body weight) to rats bearing the AH-130 Yoshida ascites hepatoma, a highly
      cachectic rat tumour. RESULTS: The treatment results in a significant improvement
      of food intake and in muscle weight (gastrocnemius, EDL and soleus). These
      beneficial effects are directly related to improved physical performance (total
      physical activity, mean movement velocity and total travelled distance).
      Administration of L-carnitine decreases proteasome activity and the expression of
      genes related with this activity, such as ubiquitin, C8 proteasome subunit and
      MuRF-1. Interestingly, L-carnitine treatment also decreases caspase-3 mRNA
      content therefore suggesting a modulation of apoptosis. Moreover, addition of 50
      MUM of L-carnitine to isolated EDL muscles results in a significant decrease in
      the proteolytic rate suggesting a direct effect. CONCLUSIONS: It can be concluded
      that L-carnitine supplementation may be a good approach for a multi-targeted
      therapy for the treatment of cancer-related cachexia.

PMID- 22608918
TI  - Clinical and economic impact of malnutrition per se on the postoperative course
      of colorectal cancer patients.
AB  - BACKGROUND & AIMS: To assess the medico-economic impact of malnutrition in
      patients who underwent surgery for colorectal cancer. METHODS: We performed post
      hoc analyses of data from the Alves et al. prospective study. Using standard
      criteria of malnutrition, 2 groups were created a posteriori: Well-nourished (WN)
      and Mal-nourished (MN) patients. The 2 groups were statistically adjusted for
      age, cancer status, and scheduled surgery. Individual costs were valued using the
      French National Cost Study. Postoperative morbidity, mortality, hospital length
      of-stay (LOS), and discharge setting were compared. We defined 3 scenarios, the
      most accurate estimate and its upper and lower limits, to assess the economic
      impact of malnutrition. RESULTS: 453 patients were included in the analyses.
      Complication and mortality rates were not significantly different between the 2
      groups. MN patients had a mean LOS 3.41 days significantly longer than WN
      patients (p = 0.017). In MN patients, the cost of hospital stay was increased by
      around 3360 ?, creating an annual impact of 10,159,436 ? for French non-profit
      hospitals. CONCLUSIONS: Malnutrition in colorectal cancer surgical patients is
      associated with an increased LOS resulting in significant budget impact. Further
      studies are needed to investigate this impact and the related cost-benefit of
      perioperative specialized nutritional support and implementation of the ERAS
      protocol in this homogeneous category of patients.

PMID- 22608919
TI  - 5-(5-(6-[(11)C]methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)pyridin-2-yl)-1H-indole
      as a potential PET radioligand for imaging cerebral alpha7-nAChR in mice.
AB  - The radiosynthesis and in vivo evaluation of 5-(5-(6-[(11)C]methyl-3,6
      diazabicyclo[3.2.0]heptan-3-yl)pyridin-2-yl)-1H-indole [(11)C]rac-(1), a
      potential PET tracer for alpha7 nicotinic acetylcholine receptors (alpha7-nAChR),
      are described. Syntheses of the nonradioactive standard rac-1 and corresponding
      desmethyl precursor 7 were achieved in several reaction steps. Radiomethylation
      of 7 with [(11)C]CH(3)I afforded [(11)C]rac-1 in an average radiochemical yield
      of 30 +/- 5% (n=5) with high radiochemical purity and an average specific
      radioactivity of 444 +/- 74 GBq/MUmol (n=5). The total synthesis time was 30 min
      from end-of-bombardment. Biodistribution studies in mice showed that [(11)C]rac-1
      penetrates the blood-brain barrier and specifically labels neuronal alpha7
      nAChRs.

PMID- 22608920
TI  - Synthesis and evaluation of 11beta-(4-substituted phenyl) estradiol analogs:
      transition from estrogen receptor agonists to antagonists.
AB  - INTRODUCTION: As part of our program to develop estrogen receptor (ER) targeted
      imaging and therapeutic agents we chose to evaluate 11beta-substituted estradiol
      analogs as a representative scaffold. Previous synthetic studies provided an
      entry into this class of compounds and other work indicated that 11beta
      (substituted aryl) estradiol analogs were potent antagonists of the ER. Little
      information existed about the specific structural features involved in the
      transition from agonism to antagonism for the 11beta-aryl estradiol analogs or
      their potential as scaffolds for drug conjugation. METHODS: We prepared and
      characterized a series of 11beta-(4-Substituted phenyl) estradiol analogs using
      modifications of existing synthetic methods. The new compounds, as well as
      standard steroidal agonists and antagonists, were evaluated as competitive
      ligands for the ERbeta-LBD. Functional assays used the induction of alkaline
      phosphatase in Ishikawa cells to determine potency of the compounds as ER
      agonists or antagonists. RESULTS: The synthetic strategy successfully generated a
      series of compounds in which the 4-substituent was sequentially modified from
      hydroxyl to methoxy to azidoethoxy/N,N-dimethylaminoethoxy and eventually to a
      prototypical 1,4-naphthoquinone-containing moiety. The new compounds all retained
      high relative binding affinity (RBA) for the ERalpha-LBD, ranging from 13-83%
      that of estradiol. No subtype selectivity was observed. More importantly, the
      transition from agonist to antagonist activity occurs at the 4-methoxy stage
      where the compound is a mixed antagonist. More notably, antagonism appeared to be
      more dependent upon the size of the 11beta-substituent than upon the nature of
      the terminal group CONCLUSIONS: We have developed a synthetic strategy that
      provides facile access to potent 11beta-(4-substituted phenyl) estradiol analogs.
      The resultant compounds retain high affinity for the ERalpha-LBD and, more
      importantly, demonstrate potent antagonist activity in cells. Large
      functionalities distal to the 11beta-phenyl ring had little additional effect on
      either affinity or efficacy, suggesting the incorporation of diverse imaging or
      biologically active groups can be attached without significantly compromising the
      ER-binding capacity. Future studies are in progress to exploit the 11beta-aryl
      estradiol analogs as potential drug delivery systems and imaging agents.

PMID- 22608922
TI  - The structures of three metabolites of the algal hepatotoxin okadaic acid
      produced by oxidation with human cytochrome P450.
AB  - Four metabolites of okadaic acid were generated by incubation with human
      recombinant cytochrome P450 3A4. The structures of two of the four metabolites
      have been determined by MS/MS experiments and 1D and 2D NMR methods using 94 and
      133 MUg of each metabolite. The structure of a third metabolite was determined by
      oxidation to a metabolite of known structure. Like okadaic acid, the metabolites
      are inhibitors of protein phosphatase PP2A. Although one of the metabolites does
      have an alpha,beta unsaturated carbonyl with the potential to form adducts with
      an active site cysteine, all of the metabolites are reversible inhibitors of
      PP2A.

PMID- 22608921
TI  - Chemical syntheses and in vitro antibacterial activity of two desferrioxamine B
      ciprofloxacin conjugates with potential esterase and phosphatase triggered drug
      release linkers.
AB  - Two desferrioxamine B-ciprofloxacin conjugates with 'trimethyl-lock' based
      linkers that are designed to release the antibiotic after esterase or phosphatase
      mediated hydrolysis were synthesized. The potential esterase-sensitive conjugate
      13 displayed moderate to good antibacterial activities against selected
      ferrioxamine-utilizing bacteria, although the activities were lower than the
      parent drug ciprofloxacin. However, the potential phophatase-sensitive conjugate
      23 was inactive against the same panel of organisms tested. These properties
      appeared to be related to the activating efficiency of the linker by the enzyme
      and to the outer membrane protein recognition of the chemically modified
      siderophore used in the conjugate.

PMID- 22608925
TI  - China's meat industry revolution: challenges and opportunities for the future.
AB  - From a very limited ration of meat only for urban citizens to the world's largest
      meat-producing country, from a handful of processing facilities in major cities
      to thousands of modern meat packing and processing plants throughout the country,
      the Chinese meat industry has gone through drastic revolutionary changes
      particularly in the last three decades. Before the national economic reform in
      the late 1970s, meat production in China was extremely limited; hence, meat was
      rationed, treated as a highly precious food, and was highly valued. However, new
      processing technology developments, as related to meat animal production,
      slaughtering, processing, and distribution have transformed the inefficient
      Chinese meat industry that prepared only a handful of traditional products into a
      vast enterprise today that is manufacturing a huge variety of fresh and further
      processed items enjoyed by the average Chinese household. Along with this
      evolution, there has been the emergence of mega-scale meat companies and rapid
      advances in meat science and technology that address many aspects of meat. This
      review will highlight some milestone changes of the Chinese meat industry and
      discuss challenges and opportunities ahead in the global market for China.

PMID- 22608924
TI  - Cytoplasmic assembly and selective nuclear import of Arabidopsis Argonaute4/siRNA
      complexes.
AB  - In plants, DNA methylation can be mediated by a class of Argonaute4 (AGO4)
      associated heterochromatic siRNAs (hc-siRNAs), through a pathway termed RNA
      directed DNA methylation (RdDM). It has been thought that RdDM is solely a
      nuclear process, as both the biogenesis and functioning of hc-siRNAs take place
      in the nucleus. In this study, we unexpectedly found that hc-siRNAs are
      predominantly present in the cytoplasm. We demonstrated that AGO4 is loaded with
      hc-siRNAs in the cytoplasm and the formation of mature AGO4/siRNA complexes
      requires HSP90 and the cleavage activity of AGO4. Intriguingly, siRNA binding
      facilitates the redistribution of AGO4 into the nucleus, likely through inducing
      conformational change that leads to the exposure of the nuclear localization
      signal (NLS). Our findings reveal an unsuspected cytoplasmic step in the RdDM
      pathway. We propose that selective nuclear import of mature AGO4/siRNA complexes
      is a key regulatory point prior to the effector stage of RdDM.

PMID- 22608923
TI  - Negative regulation of the stability and tumor suppressor function of Fbw7 by the
      Pin1 prolyl isomerase.
AB  - Fbw7 is the substrate recognition component of the Skp1-Cullin-F-box (SCF)-type
      E3 ligase complex and a well-characterized tumor suppressor that targets numerous
      oncoproteins for destruction. Genomic deletion or mutation of FBW7 has been
      frequently found in various types of human cancers; however, little is known
      about the upstream signaling pathway(s) governing Fbw7 stability and cellular
      functions. Here we report that Fbw7 protein destruction and tumor suppressor
      function are negatively regulated by the prolyl isomerase Pin1. Pin1 interacts
      with Fbw7 in a phoshorylation-dependent manner and promotes Fbw7 self
      ubiquitination and protein degradation by disrupting Fbw7 dimerization.
      Consequently, overexpressing Pin1 reduces Fbw7 abundance and suppresses Fbw7's
      ability to inhibit proliferation and transformation. By contrast, depletion of
      Pin1 in cancer cells leads to elevated Fbw7 expression, which subsequently
      reduces Mcl-1 abundance, sensitizing cancer cells to Taxol. Thus, Pin1-mediated
      inhibition of Fbw7 contributes to oncogenesis, and Pin1 may be a promising drug
      target for anticancer therapy.

PMID- 22608926
TI  - Changing trends in antimicrobial susceptibility of Streptococcus pneumoniae
      isolates in Taiwan, 2006-2007.
AB  - BACKGROUND: Multiple antibiotic-resistant clones of Streptococcus pneumoniae have
      spread throughout the world and continue to evolve under the selective pressure
      of antibiotics and vaccines. The aim of this study is to assess the
      susceptibility of S. pneumoniae isolates and to analyze the resistance trends in
      Taiwan. METHODS: Antimicrobial susceptibility tests were performed on 152
      nonmeningeal isolates of S. pneumoniae that were collected from 13 different
      hospitals around Taiwan from 2006-2007. Tests were performed using the broth
      microdilution method according to recommendations of the Clinical and Laboratory
      Standards Institute. RESULTS: The minimal inhibitory concentrations
      (MIC(50)/MIC(90)) of penicillin, cefotaxime, vancomycin, and moxifloxacin were
      0.5/1.0, 0.25/1.0, 0.25/0.5, and 0.06/0.12 MUg/mL, respectively. The
      susceptibility rates of penicillin, cefotaxime, vancomycin, and moxifloxacin were
      99.3%, 99.3%, 100%, and 98.7%, respectively. However, if the meningitis
      breakpoints were applied to these nonmeningeal isolates, the susceptibility rates
      of penicillin and cefotaxime were reduced to 18.4% and 76.3%, respectively.
      Compared with the findings from previous studies in Taiwan, our results show that
      the percentage of S. pneumoniae isolates with a penicillin MIC of 0.12-1.0 MUg/mL
      increased from 43.3% in 1996-1997 to 73.7% in 2006-2007 (p < 0.001). The
      percentage of S. pneumoniae isolates with a cefotaxime MIC of 1.0 MUg/mL
      increased from 11.3% in 1996-1997 to 23.0% in 2006-2007 (p < 0.001). Regarding
      the serial MIC intervals of the four antimicrobial agents, there was no
      significant difference between bacteremic and nonbacteremic isolates. CONCLUSION:
      Although nonmeningeal S. pneumoniae isolates remained susceptible to penicillin,
      the proportion of isolates with a penicillin MIC of 0.12-1.0 MUg/mL or cefotaxime
      MIC of 1.0 MUg/mL increased during the past decade in Taiwan. The ever-increasing
      resistance of S. pneumoniae has a great impact on the treatment of meningitis.

PMID- 22608927
TI  - Glenohumeral contact pressure in a simulated active compression test using
      cadaveric shoulders.
AB  - BACKGROUND: The active compression test has been described to detect superior
      labrum anterior and posterior (SLAP) lesions. Some have speculated that contact
      between the lesser tuberosity and the superior glenoid in the testing position
      causes a positive test. This study evaluated the location of peak glenohumeral
      contact pressures during a simulated active compression test in a cadaveric model
      with and without SLAP lesions. MATERIALS AND METHODS: Six specimens were tested.
      A pressure sensor was used to record glenohumeral contact, and a motion analysis
      system was used to measure humeral head translation. Contact pressures and
      translations were measured during serial deltoid and biceps loads. These were
      repeated for small and large SLAP lesions. RESULTS: There was a notable shift in
      the location of peak contact pressure from the anterior-inferior glenoid to the
      anterior-superior glenoid with increasing deltoid load. Deltoid loading
      translated the humeral head posteriorly relative to the glenoid. Conversely,
      biceps loads countered the pull of the deltoid only when the biceps load was
      greater than the deltoid load. The SLAP tears did not significantly alter the
      degree of humeral head translation or location of the contact pressures.
      CONCLUSIONS: In the active compression test, the posterior capsule is taut and
      the anterior capsule is lax, which permits the deltoid to translate the humeral
      head posteriorly. This shift in the peak contact pressure to the superior glenoid
      may elicit a positive active compression test. LEVEL OF EVIDENCE: Basic Science
      Study, Biomechanics, Cadaver Model.

PMID- 22608928
TI  - Complications associated with open coracoid transfer procedures for shoulder
      instability.
AB  - BACKGROUND: Interest has been maintained in the use of coracoid transfer
      procedures for recurrent shoulder instability despite the significant potential
      for serious complications. A comprehensive systematic review of the literature
      was performed to quantify and characterize the complication rate associated with
      these procedures to better inform practicing surgeons and their patients.
      MATERIALS AND METHODS: Medline, Excerpta Medica Database (EMBASE), and the
      Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases were
      searched for therapeutic studies published between 1985 and 2011. Data regarding
      complications was extracted from selected articles in a standardized manner.
      Complication rates were determined and expressed as percentages with 95%
      confidence intervals. RESULTS: Included were 30 studies describing the results of
      1658 coracoid transfer procedures. Repeat surgery was documented in 4.9% +/- 1.0%
      of cases. Recurrent instability occurred in 6.0% +/- 1.2%. Hardware complications
      occurred in 6.5% +/- 1.3%. Collectively, the rate of graft nonunion, fibrous
      union, or postoperative graft migration was 10.1% +/- 1.6%; graft osteolysis
      occurred in 1.6% +/- 0.7%. There was a 1.2% +/- 0.8% rate of nerve palsy.
      Surgical site infection occurred in 1.5% +/- 0.7%. Intraoperative fractures
      occurred in 1.1 +/- 0.6%. CONCLUSION: Coracoid transfers for shoulder instability
      can improve shoulder stability with acceptable recurrence rates. They are
      challenging procedures associated with a broad range and significant incidence of
      complications. A detailed appreciation of anatomy and meticulous attention to
      technical detail, particularly graft placement, is key to reducing complications.
      These procedures may be best indicated in the setting of glenoid or humeral bony
      deficiency, although efficacy over open capsular procedures remains equivocal.

PMID- 22608929
TI  - Reconstruction of the sternoclavicular joint in active patients with the figure
      of-eight technique using hamstrings.
AB  - BACKGROUND: Dislocations of the sternoclavicular joint are rare injuries caused
      by massive forces applied to the joint. A high rate of complications has been
      reported following this injury emphasizing the importance of an accurate
      diagnosis and therapy. METHODS: We report a series of patients with chronic
      anterior or posterior sternoclavicular instability treated with figure-of-eight
      gracilis- or semitendinosus-tendon reconstruction. Tendon grafts were collected
      from the patient's ipsilateral knee. Preoperative and postoperative DASH scores
      were compared to evaluate the outcome. RESULTS: Six patients (mean age, 22 years;
      range 15-46; male = 3; female = 3) were included. The patients sustained an
      isolated dislocation of the sternoclavicular joint resulting from a high-energy
      trauma. Anterior instability was observed in 3 patients, posterior instability in
      2 patients and the remaining patient showed multidirectional instability. The
      mean time from injury to operation was 8 months (range, 4-33). The semitendinosus
      tendon was used in 4 patients, the gracilis tendon in 2 patients, respectively.
      Follow-up examination was after 22 months (range, 14-34). The DASH score improved
      from 54.3 points (range, 45.7-68.8) preoperatively to 28.8 points (range, 25.8
      34.5) postoperatively. All patients returned to full activity without limitations
      including competitive contact sports. CONCLUSION: Stabilization of the
      sternoclavicular joint with the figure-of-eight technique seems to be a feasible
      alternative for young and active patients with remaining instability following
      conservative treatment.

PMID- 22608930
TI  - The function of the clavicle on scapular motion: a cadaveric study.
AB  - HYPOTHESIS: The clavicle serves as a strut between the thorax and scapula, and
      lack of this function could affect shoulder mobility. We hypothesized that
      clavicular discontinuity changes shoulder kinematics, particularly affecting
      scapular motion. MATERIALS AND METHODS: The study used 14 cadaveric shoulders.
      Cadavers were stabilized in the sitting position. Manual elevation in the
      sagittal, scapular, and coronal planes was performed in the intact and clavicular
      discontinuity models. The thorax-scapula distance and 3-dimensional scapular
      motion during shoulder elevation were recorded using an electromagnetic tracking
      device. The differences between the 2 experimental models at each position were
      analyzed. RESULTS: Clavicular discontinuity resulted in a decreased thorax
      scapula distance and in reduced external rotation, upward rotation, and posterior
      tilting of the scapula. The kinematic changes were observed during elevations in
      all 3 planes but were greatest in the sagittal plane compared with the scapular
      and coronal planes. CONCLUSIONS: The findings of this study revealed that
      discontinuity of the clavicle affects shoulder kinematics. Because of its
      anatomic shape and position, the clavicle stabilizes the external, upward, and
      posterior rotation of the scapula during arm movement. This function of the
      clavicle may assist glenohumeral joint motion and help prevent subacromial
      impingement. LEVEL OF EVIDENCE: Basic Science Study, Biomechanics, Cadaver Model.

PMID- 22608931
TI  - The anterior deltoid's importance in reverse shoulder arthroplasty: a cadaveric
      biomechanical study.
AB  - BACKGROUND: Frequently, patients who are candidates for reverse shoulder
      arthroplasty have had prior surgery that may compromise the anterior deltoid
      muscle. There have been conflicting reports on the necessity of the anterior
      deltoid thus it is unclear whether a dysfunctional anterior deltoid muscle is a
      contraindication to reverse shoulder arthroplasty. The purpose of this study was
      to determine the 3-dimensional (3D) moment arms for all 6 deltoid segments, and
      determine the biomechanical significance of the anterior deltoid before and after
      reverse shoulder arthroplasty. METHODS: Eight cadaveric shoulders were evaluated
      with a 6-axis force/torque sensor to assess the direction of rotation and 3D
      moment arms for all 6 segments of the deltoid both before and after placement of
      a reverse shoulder prosthesis. The 2 segments of anterior deltoid were unloaded
      sequentially to determine their functional role. RESULTS: The 3D moment arms of
      the deltoid were significantly altered by placement of the reverse shoulder
      prosthesis. The anterior and middle deltoid abduction moment arms significantly
      increased after placement of the reverse prosthesis (P < .05). Furthermore, the
      loss of the anterior deltoid resulted in a significant decrease in both abduction
      and flexion moments (P < .05). CONCLUSION: The anterior deltoid is important
      biomechanically for balanced function after a reverse total shoulder
      arthroplasty. Losing 1 segment of the anterior deltoid may still allow abduction;
      however, losing both segments of the anterior deltoid may disrupt balanced
      abduction. Surgeons should be cautious about performing reverse shoulder
      arthroplasty in patients who do not have a functioning anterior deltoid muscle.

PMID- 22608932
TI  - Sensitivity and positive predictive value of magnetic resonance imaging in the
      diagnosis of elastofibroma dorsi: review of fourteen cases.
AB  - BACKGROUND: Elastofibroma dorsi (ED) is a benign soft tissue tumor that
      classically presents as an ill-defined mass at the inferior pole of the scapula.
      Several studies have indicated the benefits of using magnetic resonance imaging
      (MRI) to identify ED. In this study, we calculate the sensitivity and positive
      predictive value (PPV) of MRI in the diagnosis of ED using histopathology as the
      gold standard diagnostic method. Clinical characteristics of ED and radiologic
      features of MRI as well as treatment options are discussed. MATERIALS AND
      METHODS: A systematic retrospective review was performed of all ED patients
      treated in our center between 1999 and 2009. MRI and histopathology samples were
      performed in all cases. The MRI sensitivity and PPV in the diagnosis of ED were
      calculated. RESULTS: A total of 15 patients who were treated within the study
      period were reviewed; of these, were 14 (3 men, 11 women) true ED cases. MRI scan
      results matched the histopathology in 14 of 15 patients; 1 false-positive patient
      was observed, and no false-negative patients (negative MRI and positive
      histopathology) were noted. The PPV and sensitivity of MRI scan in the diagnosis
      of ED were 93.3% (95% confidence interval, 68.0%-100.0%) and 100% (95% confidence
      interval, 75.2%-100.0%) respectively. CONCLUSIONS: MRI is a useful tool for
      assessment of ED and can potentially help avoid the need for unnecessary biopsy
      and surgery, especially in the asymptomatic patient.

PMID- 22608933
TI  - Sensory innervation of rat contracture shoulder model.
AB  - BACKGROUND: To date, few studies have investigated the cause of pain experienced
      by patients with frozen shoulder. The purposes of this study were to establish a
      rat contracture model and clarify the innervation pattern of the glenohumeral
      (GH) joint and subacromial bursa (SAB) using immunohistochemistry in the dorsal
      root ganglion (DRG) neurons. MATERIALS AND METHODS: The rat contracture models
      were made by tying the animal's humerus and scapula with No. 2-0 FiberWire
      (Arthrex, Naples, FL, USA). Contracture was confirmed on x-ray images taken 8
      weeks after the operation. Subsequently, two kinds of neurotracers, Fluoro-Gold
      (FG) (Fluorochrome, Denver, CO, USA) and 1,1'-dioctadecyl-3,3,3',3'-tetramethyl
      indocarbocyanine perchlorate (DiI) (Molecular Probes, Eugene, OR, USA), were used
      to detect the GH joints and SAB separately. FG tracers were injected into GH
      joints, and DiI tracers were injected into the SAB. At 7 days after injection,
      DRGs were harvested between C1 and T1. Immunohistochemistry by use of calcitonin
      gene-related peptide (CGRP) was performed. CGRP is thought to be one of the
      causes of pain sensation in joint disease. We evaluated the percentages of FG
      labeled CGRP-immunoreactive (CGRP-ir) neurons in the total number of FG-labeled
      neurons and of DiI-labeled CGRP-ir neurons in the total number of DiI-labeled
      neurons. RESULTS: Abduction and total arc of the rotation were statistically
      significantly decreased in the contracture group. Furthermore, the percentage of
      CGRP-ir DRG neurons was significantly higher in the contracture group in both the
      GH joint and SAB. CONCLUSION: These results show that pain sensation in rat
      shoulder contracture may be induced by the up-regulation of CGRP expression in
      DRG neurons.

PMID- 22608934
TI  - Kerlan-Jobe Orthopaedic Clinic overhead athlete scores in asymptomatic
      professional baseball pitchers.
AB  - BACKGROUND: The Kerlan-Jobe Orthopaedic Clinic (KJOC) Shoulder and Elbow score is
      a subjective questionnaire that has been validated and been shown to be more
      specific in overhead athletes than the American Shoulder and Elbow Surgeons
      scale. The purpose of this study was to determine a mean KJOC score and
      reasonable range of KJOC scores within which a healthy asymptomatic professional
      baseball pitcher will fall. It was hypothesized that healthy professional
      baseball pitchers would have very high KJOC scores. MATERIALS AND METHODS: KJOC
      questionnaires were given to all healthy pitchers before the start of the season
      at all levels in 1 professional Minor League system. Pitchers were asked to
      complete the questionnaire upon reporting to their AAA, AA, or A affiliate team.
      Any pitcher starting the season on the disabled list was excluded from the study.
      RESULTS: KJOC scores were returned by 44 pitchers. The mean score for all
      pitchers was 94.82 (95% confidence interval, 92.94-96.70). The mean score for
      each question was greater than 9 of 10. The mean score for the AAA affiliate was
      significantly higher than that for the AA affiliate (P = .015). No other
      significant differences in scores were found between class levels or groups based
      on professional playing experience. CONCLUSION: Only 7 of 44 healthy asymptomatic
      pitchers (16%) had a KJOC score below 90. Therefore, we believe that the KJOC
      score is an accurate assessment for overhead athletes and normal values should be
      greater than 90. Anything below this value could be a potential cause for concern
      for team physicians. LEVEL OF EVIDENCE: Basic Science, Survey Study, Healthy
      Subjects.

PMID- 22608935
TI  - Kinetics and thermodynamics of heavy metal ions sequestration onto novel Nauclea
      diderrichii seed biomass.
AB  - This study reports the sequestration of Cd(II) and Hg(II) using a new biosorbent,
      Nauclea diderrichii seed biomass. Experimental data obtained were fitted into
      kinetic and thermodynamic models. Experimental data fitted best into pseudo
      second order kinetic model among others. Results obtained kinetically revealed
      that the biosorption of Cd(II) and Hg(II) using N. diderrichii seed biosorbent
      increased with increase in temperature. At the highest temperature, which was 333
      K, the highest amount of metal biosorbed, q(e), for Cd(II) and Hg(II) obtained
      were 6.30 and 6.15 mg/g respectively. The biosorption of Cd(II) was kinetically
      faster than that of Hg(II), the highest initial biosorption rates for Cd(II) and
      Hg(II) were 56.19 and 4.39 mg/g min respectively. Thermodynamic parameters
      obtained by Erying equation from this study revealed that the biosorption process
      was spontaneous, feasible, endothermic with a decrease in the degree of chaos in
      the biosorption system.

PMID- 22608936
TI  - Modelling bioprocesses and membrane fouling in membrane bioreactor (MBR): a
      review towards finding an integrated model framework.
AB  - The bioprocesses taking place in activated sludge wastewater treatment system
      itself are characterized by great complexity and yet incomplete understanding of
      some of the phenomena involved. The MBR technology inherent deficiencies for its
      simulation due to additional intrinsic complexities resulting from the
      interaction between concurrently occurring and dynamic biological processes with
      membrane filtration and the straightforward adoption of the activated sludge
      models' (ASM) frameworks or their modified variations. In this backdrop, this
      paper compiles a brief overview of the previous developments to the current state
      of-the-art mathematical modelling approaches of the MBR system. With extended
      discussions on particular topics such as applications of modified ASMs to MBR
      modelling, ASM extensions incorporating soluble microbial products
      (SMP)/extracellular polymeric substances (EPS) concepts, this paper also provides
      a guide for different end-users of mathematical models of MBR systems.

PMID- 22608937
TI  - Perspectives on anaerobic membrane bioreactor treatment of domestic wastewater: a
      critical review.
AB  - Interest in increasing the sustainability of water management is leading to a
      reevaluation of domestic wastewater (DWW) treatment practices. A central goal is
      to reduce energy demands and environmental impacts while recovering resources.
      Anaerobic membrane bioreactors (AnMBRs) have the ability to produce a similar
      quality effluent to aerobic treatment, while generating useful energy and
      producing substantially less residuals. This review focuses on operational
      considerations that require further research to allow implementation of AnMBR DWW
      treatment. Specific topics include membrane fouling, the lower limits of
      hydraulic retention time and temperature allowing for adequate treatment,
      complications with methane recovery, and nutrient removal options. Based on the
      current literature, future research efforts should focus on increasing the
      likelihood of net energy recovery through advancements in fouling control and
      development of efficient methods for dissolved methane recovery. Furthermore,
      assessing the sustainability of AnMBR treatment requires establishment of a
      quantitative environmental and economic evaluation framework.

PMID- 22608938
TI  - A mini-review on membrane fouling.
AB  - During the last decades, the interest of using membrane technology has emerged in
      wastewater treatment as well as drinking water and process water production.
      However, the impediment of the membrane technology is the fouling problem and
      consequently higher operating and membrane replacement cost. Hence, better
      understanding of membrane fouling is not only the key to solve the problems, but
      also is one of the main factors driving membrane technology forward. This mini
      review paper identifies the major foulants and the principal membrane fouling
      mechanisms such as pore blocking, cake formation, concentration polarization,
      organic adsorption, inorganic precipitation and biological fouling. It also gives
      a holistic review about different fouling phenomena during the application of
      membrane separation technologies in water and wastewater treatment, with specific
      references to various problems, membranes, treatment processes and its practical
      applications.

PMID- 22608939
TI  - Effect of S-TE (solubilization by thermophilic enzyme) digestion conditions on
      hydrogen production from waste sludge.
AB  - S-TE (solubilization by thermophilic enzyme) digestion was always used for waste
      sludge solubilization and reduction with the theory of lysis enzyme secreted by
      thermophilic bacteria. The effects of pretreated times, pH and sludge
      concentrations on S-TE digestion were investigated to determine the optimum S-TE
      conditions on hydrogen fermentation from waste sludge. The experimental results
      showed that the protein, carbohydrate and SCOD (soluble chemical oxygen demand)
      were released after S-TE pretreatment, and the optimal conditions on sludge
      solubilization were 12-16 h, pH 7-9 and 4.31 g/L TSS, respectively. The optimal S
      TE conditions on hydrogen yields were 8h, pH 6 and 6.83 g/L TSS (total suspended
      solid), and the maximum hydrogen yields were 30.80 ml/g VSS (volatile suspended
      solid), 33.75 ml/g VSS and 42.90 ml H2/g VSS, respectively. It was concluded that
      the optimal S-TE digestion conditions on sludge solubilization were different
      from that on hydrogen production.

PMID- 22608940
TI  - Considerations on methylmercury (MeHg) treatments in in vitro studies.

PMID- 22608941
TI  - Atypical presentation of geniculate ganglion venous malformation in a child:
      conductive hearing loss without facial weakness.
AB  - We describe an unusual presentation of geniculate ganglion venous malformation, a
      rare facial nerve lesion, emphasizing the importance of the differential
      diagnosis, imaging characteristics, and controversies in management. A child
      presented with moderate right-sided conductive hearing loss and a House-Brackmann
      grade I facial nerve function bilaterally. Computed tomography and magnetic
      resonance imaging showed a mass demonstrating features consistent with a
      geniculate ganglion venous malformation. To our knowledge, this is the first
      pediatric case of geniculate ganglion venous malformation presenting solely with
      conductive hearing loss. Proper management requires differentiating this
      condition from other geniculate and temporal bone lesions.

PMID- 22608942
TI  - S-shaped tracheostoma in pediatric tracheostomy using three-dimensional sigma
      plasty--a novel technique to possibly reduce procedure related complications.
AB  - OBJECTIVES: We have designed a technique of tracheostomy in pediatric patients
      with S-shaped incision on the tracheal wall which we think, provides a larger
      cross-sectional area of stoma and facilitates easier insertion of tracheostomy
      tube and thus helped in reducing early and late complications associated with it
      in our series. TECHNIQUE: The trachea was exposed in midline by a vertical skin
      incision. In order to make S-shaped tracheostoma, second tracheal ring was
      identified. The conventional vertical incision was made in second tracheal ring
      and then extended at both its ends laterally in the inter-cartilaginous space
      parallel to the tracheal cartilage in the opposite direction to make the incision
      S-shaped. The trachea was dilated with tracheal dilator and appropriate size of
      tracheostomy tube was then placed into the trachea. RESULTS: S-shaped
      tracheostomy was performed in 40 children with mean age of 6.36 years (age range
      is 2-12) required for airway maintenance or prolonged ventilatory support. The
      incidence of early complications was quite less in our patients (ranged from 0 to
      5%). There was no incidence of excessive intra-operative bleeding or injury to
      surrounding structures causing subcutaneous emphysema or vocal cord palsy. One
      patient developing pneumothorax after the procedure was managed conservatively.
      There was no incidence of tracheo-esophageal fistula, suprastomal collapse or
      difficulty in decannulation on 9 months of follow up related to our technique.
      However, one of the patients developed early trachietis and cutaneous peristomal
      granulomas and 2 patients developed late trachietis which was treated
      conservatively. CONCLUSION: S-shaped tracheoplasty, a new pediatric tracheotomy
      technique has resulted in a quantifiable reduction in the risk of the early and
      late complications in our series. Hence, we feel that this new technique is a
      better alternative to existing methods but larger randomized controlled studies
      are required before universal adoption of this technique.

PMID- 22608943
TI  - Oral and oropharyngeal impalement injury in pediatric patients--focus on rural
      environment.
AB  - OBJECTIVE: This article describes a case series of oral and oropharyngeal
      impalement injuries in pediatric patients and highlights the peculiar etiological
      role of the rural environment. STUDY DESIGN: The records of nine pediatric
      patients who presented with oropharyngeal impalement injuries were reviewed. The
      patients were all from various rural areas of South Africa. The article focuses
      on the challenges and risk of post-impalement injury infection in the context of
      a rural environment. RESULTS: There were eight boys and one girl. The ages of the
      study participants ranged from 2 to 10 years. Object-to-head injury was the
      predominant etiopathogenic mechanism (six cases) compared with head-to-object
      injury (three cases). Six out of nine lesions were shallow. The hard palate was
      the single most commonly affected site. Two cases (2/9) of post-impalement injury
      infection were recorded. CONCLUSION: Although the risk of infection post
      oropharyngeal impalement injury is reported to be low, it remains, however, a
      legitimate concern in cases occurring in the rural environment. The specific
      challenges in terms of health infrastructures in the rural environment,
      especially in developing countries, may have an impact on the ways oropharyngeal
      impalement injuries are managed.

PMID- 22608944
TI  - Epidemiology of early childhood caries: clinical application.
AB  - Early childhood caries (ECC) is the most communicable and preventable disease
      process in children younger than 5 years. Instead of moving in the direction
      epidemiologists would like to see, incidence rates of ECC are moving upward from
      the targeted 11%, as outlined by Healthy People 2010. The nursing profession can
      address risk factors, treatment options, and the need to increase awareness of
      the transmission of ECC along with prevention efforts. Efforts made by nursing
      students in a service-learning project to increase awareness of ECC are outlined.
      In addition, intervention strategies disseminated by advanced nurse practitioners
      and nurse educators to augment these efforts are summarized. 

PMID- 22608945
TI  - Korean American parental depressive symptoms and children's mental health: the
      mediating role of parental acceptance-rejection.
AB  - This study explored the mediating role of parental acceptance-rejection in the
      relationship between parental depressive symptoms and children's mental health.
      Self-report data were gathered from 95 mothers and 91 fathers of children (ages 5
      10 years) in Korean American families. For mothers and fathers, the relationship
      between parental depressive symptoms and child psychosocial problems was mediated
      by parenting behaviors, with parental rejection being a much stronger mediator
      than parental acceptance. For fathers, the relationship between fathers'
      depressive symptoms and child social competence was mediated by parenting, with
      fathers' parental rejection being a slightly stronger mediator than fathers'
      parental acceptance.

PMID- 22608946
TI  - The occurrence and distribution of pharmaceutical compounds in the effluents of a
      major sewage treatment plant in Northern Taiwan and the receiving coastal waters.
AB  - The pharmaceutical residues in waste water from the largest sewage treatment
      plant (STP) in Northern Taiwan and in seawater around the effluent discharged
      area were determined. An environmental risk assessment for the marine environment
      was conducted based on the environment risk quotient (ERQ). The concentrations of
      the analyzed compounds in STP influent and effluent were generally higher than
      those found in coastal seawater. Relatively higher values were found at the
      estuarine mouth and the discharged area, suggesting that the STP effluent is a
      point source. The removal efficiency and half life of the analyzed compounds were
      6.3-46.8% and 3-18 days, respectively. The ERQ value theoretical calculation was
      generally greater than 1. However, when the measured concentrations replaced the
      predicated concentrations, the ERQ values were considerably lower than 1.
      Therefore, our results call for a re-evaluation of the risks posed by
      pharmaceuticals to coastal marine ecosystems in Northern Taiwan.

PMID- 22608947
TI  - [Aggressive Kaposi's sarcoma related to corticosteroids or immune reconstitution
      syndrome?].

PMID- 22608948
TI  - Pulmonary hypertension complicating sarcoidosis.
AB  - Pulmonary hypertension is a challenging complication of sarcoidosis, which
      reported rates of prevalence largely depend on the advancement of pulmonary
      disease. About 6% of unselected sarcoidosis patients suffer from PH. Although
      destruction of the distal capillary bed and resultant hypoxemia are important,
      the mechanisms of sarcoidosis-PH are multifactorial, including specific
      vasculopathy, local increased vasoreactivity, extrinsic compression of pulmonary
      vessels and portal hypertension. As a result, a proportion of patients exhibit
      "out of proportion" PH, i.e. more severe than expected from functional impairment
      (mean PAP>35-40mmHg). The sarcoidosis vasculopathy prevails in the venous side,
      reflecting the spreading of granulomatous process, and can cause pulmonary veno
      occlusive disease. The responsibility of left-heart dysfunction is probably
      underestimated by echocardiography. There is no validated screening algorithm for
      the detection of sarcoidosis-PH but recent studies have underlined the role of
      right heart catheterisation to exclude post-capillary PH. PH carries a poor
      prognosis in sarcoidosis patients, with a significantly increased morbidity and
      mortality. Management of sarcoidosis-PH mainly relies on supportive therapy
      (supplemental oxygen and diuretics as needed) and lung transplantation in
      otherwise eligible patients. Rare cases of sarcoidosis-PH with nonfibrotic
      pulmonary disease respond to corticosteroids. Data on the efficacy and safety of
      PAH agents are scarce and discrepant. Further controlled trials are warranted and
      should integrate the concept of disproportionate PH in their design.

PMID- 22608949
TI  - Cardiac sarcoidosis.
AB  - The prognosis of sarcoidosis often considered as "benign" is significantly
      changed in the presence of a cardiac localization. An in-depth interview, a
      clinical examination together with ECG are often for most of sarcoidosis. Certain
      conditions (severe multisystemic sarcoidosis, rares localizations in particular
      neurological, renal, gastric) lead to necessary investigations: Holter ECG,
      echocardiography, thallium scintigraphy with dipyridamole test, PET scanner and
      MRI in order to identify infraclinical presentations. Diagnosis relies on
      guidelines of Japansese criteria, but can benefit from MRI and PET scanner even
      though their place is not yet clearly defined in clinical pratice. Diagnosing
      cardiac sarcoidosis means deciding an immunosuppressive treatment. It is highly
      important to gather all criteria to validate a consistent diagnosis or at least a
      high probability. In order to best adapt therapy, a coordinated patient care
      involving the cardiologist and the sarcoidosis specialist is necessary.

PMID- 22608950
TI  - Risk-prediction model for ischemic stroke in patients hospitalized with an acute
      coronary syndrome (from the global registry of acute coronary events [GRACE]).
AB  - The risk of stroke in patients hospitalized with an acute coronary syndrome (ACS)
      ranges from <1% to >= 2.5%. The aim of this study was to develop a simple
      predictive tool for bedside risk estimation of in-hospital ischemic stroke in
      patients with ACS to help guide clinicians in the acute management of these high
      risk patients. Data were obtained from 63,118 patients enrolled from April 1999
      to December 2007 in the Global Registry of Acute Coronary Events (GRACE), a
      multinational registry involving 126 hospitals in 14 countries. A regression
      model was developed to predict the occurrence of in-hospital ischemic stroke in
      patients hospitalized with an ACS. The main study outcome was the development of
      ischemic stroke during the index hospitalization for an ACS. Eight risk factors
      for stroke were identified: older age, atrial fibrillation on index
      electrocardiogram, positive initial cardiac biomarkers, presenting systolic blood
      pressure >= 160 mm Hg, ST-segment change on index electrocardiogram, no history
      of smoking, higher Killip class, and lower body weight (c-statistic 0.7). The
      addition of coronary artery bypass graft surgery and percutaneous coronary
      intervention into the model increased the prediction of stroke risk. In
      conclusion, the GRACE stroke risk score is a simple tool for predicting in
      hospital ischemic stroke risk in patients admitted for the entire spectrum of
      ACS, which is widely applicable to patients in various hospital settings and will
      assist in the management of high-risk patients with ACS.

PMID- 22608951
TI  - Dilation of the ascending aorta after balloon valvuloplasty for aortic stenosis
      during infancy and childhood.
AB  - Dilation of the ascending aorta (AA) is common in patients with a bicuspid aortic
      valve. The natural history of the aortic root and AA and the risk factors for
      dilation have not been characterized in patients with congenital aortic stenosis
      (AS) treated with balloon valvuloplasty during childhood. The present study was
      performed to determine the prevalence of aortic dilation in patients with
      congenital AS before and up to 20 years after balloon valvuloplasty performed
      during childhood. In patients who underwent balloon valvuloplasty for AS at age
      <= 18 years from 1984 to 2005, the aortic diameter measurements before
      intervention and at 5-year intervals afterward were recorded and the Z scores
      calculated. Among 156 patients (median age 1.5 years at valvuloplasty), the AA Z
      scores were significantly larger than normal before intervention (median Z score
      1.5) and at all follow-up points (all p <0.001). Using mixed modeling, with time
      as a categorical variable (before intervention, 5-year window, 10-year window,
      and so forth), the mean AA Z score was greater at all postvalvuloplasty points
      than before the intervention, with mean Z score increases of 1.20 at 5 years and
      2.11 at 20 years (p <0.001). Moderate or greater aortic regurgitation early after
      valvuloplasty was associated with greater AA Z scores than mild or less aortic
      regurgitation, with a progressive difference over time. More significant residual
      AS after valvuloplasty was associated with lower AA Z scores over time. In
      conclusion, AA dilation is common in children with congenital AS and continues to
      progress over many years after balloon valvuloplasty.

PMID- 22608952
TI  - Meta-analysis of cardiovascular outcomes with dronedarone in patients with atrial
      fibrillation or heart failure.
AB  - Dronedarone is a benzofuran derivative approved by the Food and Drug
      Administration to decrease the risk of cardiovascular hospitalization in patients
      with paroxysmal or persistent atrial fibrillation (AF) and associated
      cardiovascular risk factors who are in sinus rhythm or will undergo
      cardioversion. There has been recent evidence to suggest that dronedarone may not
      have a favorable safety profile. We decided to evaluate all available evidence on
      the cardiovascular safety of this drug. A systematic search was made of the
      PubMed, CENTRAL, and EMBASE databases for randomized controlled trials from 1966
      through 2011 comparing dronedarone to comparators in AF/heart failure.
      Intervention was dronedarone for AF for some studies and heart failure for
      others. Comparators included standard medical therapy and/or placebo and
      amiodarone for 1 study. Outcomes assessed were all-cause mortality,
      cardiovascular mortality, ventricular arrhythmias, embolic events, acute coronary
      syndrome, heart failure exacerbations, and hospitalization rates in the
      intervention versus comparator group at the end of >= 3 months of follow up with
      abstraction of data by 1 author. Seven randomized controlled trials were included
      in our analysis. Dronedarone use was associated with a trend toward worse all
      cause and cardiovascular mortalities and increased heart failure exacerbations.
      It also showed numerically higher event rates for all other outcome events except
      acute coronary syndrome. Our pooled analysis showed increased all-cause and
      cardiovascular mortalities and increased heart failure exacerbations with use of
      dronedarone across a wide spectrum of populations. In conclusion, we recommend
      exercising caution using dronedarone, especially in patients with cardiovascular
      risk factors.

PMID- 22608953
TI  - HSPB1 gene polymorphisms predict risk of mortality for US patients after
      radio(chemo)therapy for non-small cell lung cancer.
AB  - PURPOSE: We investigated potential associations between single-nucleotide
      polymorphisms (SNPs) in the heat shock protein beta-1 (HSPB1) gene and overall
      survival in US patients with non-small cell lung cancer (NSCLC). METHODS AND
      MATERIALS: Using available genomic DNA samples from 224 patients with NSCLC
      treated with definitive radio(chemo)therapy, we genotyped 2 SNPs of HSPB1 (NCBI
      SNP nos. rs2868370 and rs2868371). We used both Kaplan-Meier cumulative
      probability and Cox proportional hazards analyses to evaluate the effect of HSPB1
      genotypes on survival. RESULTS: Our cohort consisted of 117 men and 107 women,
      mostly white (79.5%), with a median age of 70 years. The median radiation dose
      was 66 Gy (range, 63-87.5 Gy), and 183 patients (82%) received concurrent
      platinum-based chemotherapy. The most common genotype of the rs2868371 SNP was CC
      (61%). Univariate and multivariate analyses showed that this genotype was
      associated with poorer survival than CG and GG genotypes (univariate hazard ratio
      [HR] = 1.39, 95% confidence interval [CI], 1.02-1.90; P=.037; multivariate HR =
      1.39; 95% CI, 1.01-1.92; P=.045). CONCLUSIONS: Our results showed that the CC
      genotype of HSPB1 rs2868371 was associated with poorer overall survival in
      patients with NSCLC after radio(chemo)therapy, findings that contradict those of
      a previous study of Chinese patients. Validation of our findings with larger
      numbers of similar patients is needed, as are mechanical and clinical studies to
      determine the mechanism underlying these associations.

PMID- 22608954
TI  - International Spine Radiosurgery Consortium consensus guidelines for target
      volume definition in spinal stereotactic radiosurgery.
AB  - PURPOSE: Spinal stereotactic radiosurgery (SRS) is increasingly used to manage
      spinal metastases. However, target volume definition varies considerably and no
      consensus target volume guidelines exist. This study proposes consensus target
      volume definitions using common scenarios in metastatic spine radiosurgery.
      METHODS AND MATERIALS: Seven radiation oncologists and 3 neurological surgeons
      with spinal radiosurgery expertise independently contoured target and critical
      normal structures for 10 cases representing common scenarios in metastatic spine
      radiosurgery. Each set of volumes was imported into the Computational Environment
      for Radiotherapy Research. Quantitative analysis was performed using an
      expectation maximization algorithm for Simultaneous Truth and Performance Level
      Estimation (STAPLE) with kappa statistics calculating agreement between
      physicians. Optimized confidence level consensus contours were identified using
      histogram agreement analysis and characterized to create target volume definition
      guidelines. RESULTS: Mean STAPLE agreement sensitivity and specificity was 0.76
      (range, 0.67-0.84) and 0.97 (range, 0.94-0.99), respectively, for gross tumor
      volume (GTV) and 0.79 (range, 0.66-0.91) and 0.96 (range, 0.92-0.98),
      respectively, for clinical target volume (CTV). Mean kappa agreement was 0.65
      (range, 0.54-0.79) for GTV and 0.64 (range, 0.54-0.82) for CTV (P<.01 for GTV and
      CTV in all cases). STAPLE histogram agreement analysis identified optimal
      consensus contours (80% confidence limit). Consensus recommendations include that
      the CTV should include abnormal marrow signal suspicious for microscopic invasion
      and an adjacent normal bony expansion to account for subclinical tumor spread in
      the marrow space. No epidural CTV expansion is recommended without epidural
      disease, and circumferential CTVs encircling the cord should be used only when
      the vertebral body, bilateral pedicles/lamina, and spinous process are all
      involved or there is extensive metastatic disease along the circumference of the
      epidural space. CONCLUSIONS: This report provides consensus guidelines for target
      volume definition for spinal metastases receiving upfront SRS in common clinical
      situations.

PMID- 22608955
TI  - The activity of a Spanish bone densitometry unit revisited under the point of
      view of FRAX.
AB  - In March 2008, FRAX, developed by Kanis and collaborators in the University of
      Sheffield and supported by the World Health Organization, became available online
      to calculate absolute risk of osteoporotic fracture in the next 10 years.
      OBJECTIVE: To analyze the risk of fracture calculated by FRAX and its
      determinants in the patients sent to a densitometry unit for bone mineral density
      (BMD) testing. METHODS: All the patients submitted by Primary Care to the
      Densitometry Unit for BMD testing underwent a self administered questionnaire to
      assess the clinical risk factors included in FRAX and a bone densitometry of
      lumbar spine and proximal femur with a DXA densitometer Hologic QDR 4500. They
      were classified as having a normal BMD, osteopenia or osteoporosis along with the
      recommendations of the International Society for Clinical Densitometry. As the
      reference population to calculate the T and Z scores, we used the one from the
      NHANES III study for femoral neck and total hip and the one from the Study of the
      Spanish Population for total spine. With the data of the questionnaire, we
      calculated, by FRAX, the absolute risk in the next ten years of having a major
      fracture (MFR) or a hip fracture (HFR). Both risks were calculated with or
      without the inclusion in the algorithm of BMD: MFR+, MFR-, HFR+ and HFR-. The
      results were recorded in an Access 2003 database and analyzed with the
      statistical package SPSS 15.0 for Windows. RESULTS: We analyzed the data from 853
      women with a mean age of 61.9 (8.9) years and a mean body mass index of 27.0
      (4.2)kg/m(2). Mean BMD at lumbar spine was 0.873 (0.127)g/cm(2); at femoral neck,
      0.704 (0.105)g/cm(2); and at total hip, 0.817 (0.107)g/cm(2). Twenty percent of
      the patients had a normal BMD, 55% had osteopenia and 25%, osteoporosis. Yet
      excluding age and body mass index, the number of fracture risk factors seems low:
      31% of the patients had no risk of fracture; 40%, had one; 22%, two; 6%, three;
      1%, four; and one patient had five. Mean MFR+ was 5.4 (4.8)%; mean MFR-, 6.3
      (5.5)%; mean HFR+, 1.5 (2.9)%; and HFR-, 2.1 (3.3)%. When BMD was included in the
      algorithm for the calculation of the risk of fracture, the risk was statistically
      lower (p<0.001), especially in patients with better BMD. CONCLUSIONS: The risk of
      fracture calculated by FRAX in the patients sent to a densitometry unit for bone
      BMD testing seems low and, probably, a better selection of the patients would
      detect a higher risk of fracture population. When the fracture risk is calculated
      with the introduction of BMD in the algorithm, it is lower than without including
      BMD.

PMID- 22608956
TI  - Anterior knee tumor as the form of presentation of a giant synovial cyst.

PMID- 22608958
TI  - Stress relaxation of trithiocarbonate-dimethacrylate-based dental composites.
AB  - OBJECTIVES: To reduce polymerization-induced shrinkage stress while maintaining
      mechanical properties, reversible addition-fragmentation chain transfer (RAFT)
      capable functional groups were incorporated into a photopolymerizable
      dimethacrylate-based dental composite. We hypothesize that the incorporation of
      trithiocarbonate-based RAFT functional groups into conventional dimethacrylate
      dental resins will reduce polymerization stress. METHODS: A trithiocarbonate
      dimethacrylate (TTCDMA) monomer, capable of undergoing radical-mediated RAFT, is
      mixed with 70 wt% BisGMA (bisphenylglycidyl dimethacrylate) and compared to a
      conventional dental resin comprised of TEGDMA (triethylene glycol dimethacrylate)
      and 70 wt% BisGMA. The shrinkage stress and methacrylate conversion were
      simultaneously measured during polymerization. The fracture toughness and elastic
      modulus were measured to evaluate the effect of the TTCDMA monomer on the
      mechanical properties. All the materials used herein were evaluated as a
      composite, including 75 wt% silica fillers. ANOVA (CI 95%) was conducted to
      assess the differences between the means. RESULTS: The TTCDMA composite exhibited
      a 65% stress reduction compared with TEGDMA-BisGMA though the reaction rate was
      slower than the conventional dental composite, owing to the additional RAFT
      reaction. The fracture toughness and elastic modulus of the TTCDMA-based
      composite were not significantly different than in the TEGDMA-based composite,
      while the T(g) was decreased by 30  degrees C to 155 +/- 2  degrees C.
      SIGNIFICANCE: Despite only replacing the reactive-diluent, significant and
      dramatic stress reduction was observed while maintaining the elastic modulus and
      fracture toughness. This new RAFT-capable monomer shows great promise to replace
      the reactive diluent in BisGMA-based dental materials. Formulation optimization
      and further exploration of other RAFT-capable functional groups will provide
      further stress reduction in dental materials.

PMID- 22608959
TI  - Clinical success and survival of indirect resin composite crowns: results of a 3
      year prospective study.
AB  - OBJECTIVES: The aim of this study was to test the new resin composite "NECO" as a
      material for indirect restorations clinically. METHODS: Forty-five patients were
      selected, of which 12 men and 33 women, with a mean age of 53. A total of 91 post
      canine indirect resin composite NECO (Heraeus Kulzer, GmbH) restorations were
      placed, of which 86 full crowns and 5 onlays. Restorations were cemented with
      either resin cement (2bond2) or resin modified glass ionomer cement (Fuji Plus).
      The restorations were evaluated 1-2 weeks (baseline), 6 months, 1, 2, and 3 years
      after placement. At these recalls, success and survival data of the abutment
      teeth were documented. Survival was defined as the restoration being in situ, and
      success as the restoration in situ without complications. RESULTS: After 3 years
      in service, the restorations showed success and survival rates of 84.8 and 91.6%,
      respectively. Cementation with Fuji Plus showed a trend (p=0.054) toward higher
      success (93.1%) and survival (100%) rates compared to cementation with 2bond2
      cement which showed success and survival rates of 81.4 and 87.9% respectively.
      Restorations on vital teeth resulted in success and survival rates of 86.8 and
      95.3% respectively, while restorations on endodontically treated teeth showed
      success and survival rates of 82.6 and 87.5%. This difference was not
      statistically significant (p=0.296). SIGNIFICANCE: Three-year success and
      survival rates of NECO restorations were 84.8 and 91.6%, respectively. The design
      of the preparation and restoration should take the material properties into
      account in order to enhance the clinical performance.

PMID- 22608957
TI  - Management of rheumatoid arthritis in Spain (emAR II). Clinical characteristics
      of the patients.
AB  - BACKGROUND: There is a wide variability in the diagnostic and therapeutic methods
      in rheumatoid arthritis (AR) in Spain, according to prior studies. The quality of
      care could benefit from the application of appropriate clinical practice
      standards; we present a study on the variability of clinical practice. METHODS:
      Descriptive review of clinical records (CR) of patients aged 16 or older
      diagnosed with RA, selected by stratified sampling of the Autonomous Communities
      in two stages per Hospital Center and patient. Collected analysis of
      sociodemographic data, evolution, follow-up, joint count, reactants, function,
      job history, Visual Analogue Scales (VAS) and other. RESULTS: We obtained valid
      information of 1,272 RA patients. The ESR, CRP and rheumatoid factor (RF) were
      regularly used parameters. The percentages of missing data in tender (TJN) and
      swollen (SJN) joint counts were 8.2% and 9.6% respectively; regarding the VAS we
      found 53.6% (patient), 59.1% (pain), and 72% in the physician VAS. CONCLUSIONS:
      Despite having clinical practice guidelines on RA, there still exists a
      significant variability in RA management in our country.

PMID- 22608960
TI  - Biofilm inhibition by an experimental dental resin composite containing
      octenidine dihydrochloride.
AB  - OBJECTIVES: The aim of the present study was to investigate an antimicrobial
      additive containing experimental resin composite with regards to its impact on
      biofilm formation under oral conditions. METHODS: Biofilms were established in
      situ on composite specimens (n=192) which contained octenidine dihydrochloride
      (ODH, 3 wt.% or 6 wt.%). Samples without antimicrobial additive served as control
      (n=96). Composite specimens were fixed on custom made splints and exposed to the
      oral cavity of six healthy volunteers for three or seven days. Biofilm formation
      was assessed by scanning electron microscopy (SEM) and fluorescence microscopy
      (FM). RESULTS: The biofilm formation was significantly reduced on ODH containing
      samples compared to controls after three as well as after seven days in situ. FM
      evaluation additionally showed a lower viability of the reduced biofilms for both
      ODH concentrations. SIGNIFICANCE: During this short term investigation,
      incorporation of ODH into resin based composite materials caused biofilm
      inhibiting effects in situ.

PMID- 22608961
TI  - Identification of a phenylacylsulfonamide series of dual Bcl-2/Bcl-xL
      antagonists.
AB  - A series of phenylacylsulfonamides has been prepared as antagonists of Bcl-2/Bcl
      xL. In addition to potent binding affinities for both Bcl-2 and Bcl-xL, these
      compounds were shown to induce classical markers of apoptosis in isolated
      mitochondria. Overall weak cellular potency was improved by the incorporation of
      polar functionality resulting in compounds with moderate antiproliferative
      activity.

PMID- 22608962
TI  - Identification, optimisation and in vivo evaluation of oxadiazole DGAT-1
      inhibitors for the treatment of obesity and diabetes.
AB  - A novel series of DGAT-1 inhibitors was discovered from an oxadiazole amide high
      throughput screening (HTS) hit. Optimisation of potency and ligand lipophilicity
      efficiency (LLE) resulted in a carboxylic acid containing clinical candidate 53
      (AZD3988), which demonstrated excellent DGAT-1 potency (0.6 nM), good
      pharmacokinetics and pre-clinical in vivo efficacy that could be rationalised
      through a PK/PD relationship.

PMID- 22608963
TI  - The design and synthesis of novel, potent and orally bioavailable N-aryl
      piperazine-1-carboxamide CCR2 antagonists with very high hERG selectivity.
AB  - A novel N-aryl piperazine-1-carboxamide series of human CCR2 chemokine receptor
      antagonists was discovered. Early analogues were potent at CCR2 but also
      inhibited the hERG cardiac ion channel. Structural modifications which decreased
      lipophilicity and basicity resulted in the identification of a sub-series with an
      improved margin over hERG. The pharmacological and pharmacokinetic properties of
      the lead compound from this series, N-(3,4-dichlorophenyl)-4-[(2R)-4
      isopropylpiperazine-2-carbonyl]piperazine-1-carboxamide, are described.

PMID- 22608964
TI  - A novel series of pyrazolylpiperidine N-type calcium channel blockers.
AB  - Selective blockers of the N-type calcium channel have proven to be effective in
      animal models of chronic pain. However, even though intrathecally delivered
      synthetic omega-conotoxin MVIIA from Conus magnus (ziconotide [Prialt(r)]) has
      been approved for the treatment of chronic pain in humans, its mode of delivery
      and narrow therapeutic window have limited its usefulness. Therefore, the
      identification of orally active, small-molecule N-type calcium channel blockers
      would represent a significant advancement in the treatment of chronic pain. A
      novel series of pyrazole-based N-type calcium channel blockers was identified by
      structural modification of a high-throughput screening hit and further optimized
      to improve potency and metabolic stability. In vivo efficacy in rat models of
      inflammatory and neuropathic pain was demonstrated by a representative compound
      from this series.

PMID- 22608965
TI  - The discovery of N-cyclopropyl-4-methyl-3-[6-(4-methylpiperazin-1-yl)-4
      oxoquinazolin-3(4H)-yl]benzamide (AZD6703), a clinical p38alpha MAP kinase
      inhibitor for the treatment of inflammatory diseases.
AB  - A novel, potent and selective quinazolinone series of inhibitors of p38alpha MAP
      kinase has been identified. Modifications designed to address the issues of poor
      aqueous solubility and high plasma protein binding as well as embedded aniline
      functionalities resulted in the identification of a clinical candidate N
      cyclopropyl-4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)
      yl]benzamide (AZD6703). Optimisation was guided by understanding of the binding
      modes from X-ray crystallographic studies which showed a switch from DFG 'out' to
      DFG 'in' as the inhibitor size was reduced to improve overall properties.

PMID- 22608966
TI  - Functional implications from the Cid1 poly(U) polymerase crystal structure.
AB  - In eukaryotes, mRNA degradation begins with poly(A) tail removal, followed by
      decapping, and the mRNA body is degraded by exonucleases. In recent years, the
      major influence of 3'-end uridylation as a regulatory step within several RNA
      degradation pathways has generated significant attention toward the responsible
      enzymes, which are called poly(U) polymerases (PUPs). We determined the atomic
      structure of the Cid1 protein, the founding member of the PUP family, in its UTP
      bound form, allowing unambiguous positioning of the UTP molecule. Our data also
      suggest that the RNA substrate accommodation and product translocation by the
      Cid1 protein rely on local and global movements of the enzyme. Supplemented by
      point mutations, the atomic model is used to propose a catalytic cycle. Our study
      underlines the Cid1 RNA binding properties, a feature with critical implications
      for miRNAs, histone mRNAs, and, more generally, cellular RNA degradation.

PMID- 22608967
TI  - Screening and in situ synthesis using crystals of a NAD kinase lead to a potent
      antistaphylococcal compound.
AB  - Making new ligands for a given protein by in situ ligation of building blocks (or
      fragments) is an attractive method. However, it suffers from inherent
      limitations, such as the limited number of available chemical reactions and the
      low information content of usual chemical library deconvolution. Here, we
      describe a focused screening of adenosine derivatives using X-ray
      crystallography. We discovered an unexpected and biocompatible chemical
      reactivity and have simultaneously identified the mode of binding of the
      resulting products. We observed that the NAD kinase from Listeria monocytogenes
      (LmNADK1) can promote amide formation between 5'-amino-5'-deoxyadenosine and
      carboxylic acid groups. This unexpected reactivity allowed us to bridge in situ
      two adenosine derivatives to fully occupy the active NAD site. This guided the
      design of a close analog showing micromolar inhibition of two human pathogenic
      NAD kinases and potent bactericidal activity against Staphylococcus aureus in
      vitro.

PMID- 22608969
TI  - Bandpass filter settings differentially affect measurement of P50 sensory gating
      in children and adults.
AB  - OBJECTIVE: This study investigated the effect of four different bandpass filter
      settings on measures of the P50 component and the signal-to-noise ratios (SNR) of
      averaged ERPs obtained from a sensory gating paradigm employing paired-click
      stimuli. METHODS: Participants were adults (n=18) 20-55years old and children
      (n=25) 5-10years old who were free of neurological disorders. RESULTS: Results
      show that the filter settings (0.23-75Hz, 10-50Hz, 10-75Hz, and 10-200Hz)
      differentially affected the P50 amplitude, noise power and SNR measures of the
      conditioning and test clicks, and P50 T/C ratios. CONCLUSIONS: The 10-50Hz filter
      setting may be optimal in studies that include only adults as these settings
      resulted in the smallest mean P50 T/C ratio, a reasonable standard deviation (SD)
      for the ratio, and the highest SNRs. The 10-200Hz filter may be the best for
      studying young children as this setting had the smallest mean and SD of P50 T/C
      ratios for these participants. SIGNIFICANCE: In studies that include both adults
      and children investigators are advised to use the 10-200Hz filter setting because
      the smaller variability of sensory gating in the child group helps ensure better
      homogeneity of variance measures between the groups.

PMID- 22608968
TI  - A position-specific distance-dependent statistical potential for protein
      structure and functional study.
AB  - Although studied extensively, designing highly accurate protein energy potential
      is still challenging. A lot of knowledge-based statistical potentials are derived
      from the inverse of the Boltzmann law and consist of two major components:
      observed atomic interacting probability and reference state. These potentials
      mainly distinguish themselves in the reference state and use a similar simple
      counting method to estimate the observed probability, which is usually assumed to
      correlate with only atom types. This article takes a rather different view on the
      observed probability and parameterizes it by the protein sequence profile context
      of the atoms and the radius of the gyration, in addition to atom types.
      Experiments confirm that our position-specific statistical potential outperforms
      currently the popular ones in several decoy discrimination tests. Our results
      imply that, in addition to reference state, the observed probability also makes
      energy potentials different and evolutionary information greatly boost
      performance of energy potentials.

PMID- 22608971
TI  - Compound group I excitatory input is differentially distributed to human soleus
      motoneurons.
AB  - OBJECTIVE: We studied whether the distribution of synaptic input from compound
      group I afferents onto the various-sized motoneurons in the human soleus muscle
      supports the size principle. METHODS: The subject lay prone on a physiotherapy
      table and electrical stimuli were delivered to the tibial nerve. The recordings
      were taken with surface electromyography (SEMG) and single motor unit (SMU)
      potentials. The relative sizes of SMUs were estimated using four different
      methods. After identifying the relative size of each SMU of the pair, normalised
      size of the H-reflex was determined using the extra spike per trigger (ESPT)
      method. RESULTS: In total 33 SMU pairs were studied to compare results obtained
      in each pair. It was found that, although the stimulus intensity was identical
      for each pair, the ESPT values were statistically larger in the bigger SMUs
      compared with the relatively smaller SMUs (p<0.05). CONCLUSIONS: We conclude
      that, within the limits of this study, compound group I excitatory input to
      soleus motoneurons in human subjects does not support the size principle which
      governs the recruitment order of motoneurons in the reduced animal preparations.
      SIGNIFICANCE: This study illustrates the importance of performing human
      experiments to confirm or reject principles obtained using reduced animal
      preparations.

PMID- 22608970
TI  - Disentangling early sensory information processing deficits in schizophrenia.
AB  - OBJECTIVE: The disentangling of early sensory information processing deficits and
      examination of their relationships to demographic and clinical factors are
      important steps for the validation of potential biomarkers and/or endophenotypes
      of schizophrenia. The aims of the present study were to characterize commonly
      used sensory event-related potential deficits, to determine whether they are (1)
      distinct from one another and (2) independently associated with important
      clinical characteristics. METHODS: MMN, P3a and RON event-related potentials
      (ERP) were recorded from schizophrenia patients (SZ; n=429) and nonpsychiatric
      comparison subjects (NCS; n=286). Subgroup analyses on demographic and clinical
      variables were performed. RESULTS: Schizophrenia patients exhibited robust ERP
      deficits at frontocentral electrodes (MMN: d=1.10; P3a: d=0.87; RON: d=0.77),
      consistent with previous studies. Each ERP component uniquely accounted for
      variance in amplitude and schizophrenia deficits. Amplitude reductions occurred
      with increasing age in both NCS and SZ patients. A small subset of patients
      prescribed combinations of 1st and 2nd generation antipsychotics exhibited
      significantly reduced MMN amplitude relative to other medication-defined
      subgroups. CONCLUSIONS: MMN, P3a, and RON are dissociable deficits with distinct
      relationships to age and medication status in schizophrenia patients, potentially
      reflecting divergent pathophysiological processes. Reduced MMN in patients taking
      multiple antipsychotic medications appear to be attributable to greater severity
      of symptoms and functional impairments, rather than a medication effect.
      SIGNIFICANCE: Independent information processing deficits in schizophrenia
      patients may differentially contribute to the commonly observed deficits in
      neurocognitive and psychosocial functioning.

PMID- 22608972
TI  - Pharmacological strategies aimed at reducing complications associated with
      coronary artery bypass graft surgery.

PMID- 22608973
TI  - NEDD8 overexpression results in neddylation of ubiquitin substrates by the
      ubiquitin pathway.
AB  - Ubiquitin and ubiquitin-like proteins use unique E1, E2, and E3 enzymes for
      conjugation to their substrates. We and others have recently reported that
      increases in the relative concentration of the ubiquitin-like protein NEDD8 over
      ubiquitin lead to activation of NEDD8 by the ubiquitin E1 enzyme. We now show
      that this results in erroneous conjugation of NEDD8 to ubiquitin substrates, such
      as p53, Caspase 7, and Hif1alpha, demonstrating that overexpression of NEDD8 is
      not appropriate for identification of substrates of the NEDD8 pathway.

PMID- 22608974
TI  - Long-term outcome and prognosis of patients with emergent periodic lateralized
      epileptiform discharges (ePLEDs).
AB  - PURPOSE: Emergent EEG (eEEG) is an EEG performed on a non-elective basis upon
      request from a clinician for a seemingly emergency indication. Little is known
      about the long-term prognosis of patients with emergent periodic lateralized
      epileptiform discharges (ePLEDs). METHODS: We analyzed the EEG and clinical
      records of patients with ePLEDs from January 2002 to December 2008. RESULTS: Out
      of 1948 eEEGs, 79 (4%) patients had ePLEDs. Sixty-three patients had ePLEDs and
      16 had eBiPLEDs (emergent bilateral periodic lateralized epileptiform
      discharges). The etiology of ePLEDs was CNS infection and inflammation (35.4%),
      stroke (32.9%), and metabolic encephalopathy (11.4%). Of the surviving 52 (65.8%)
      patients with ePLEDs, 34 (65.4%) had persistent seizures during a mean follow-up
      of 28 months (range 12-72 months). Seizure as the initial presentation was more
      commonly seen in children as compared to adults (64% versus 31%, p=0.005). CNS
      infection and inflammation were also seen more frequently in the pediatric age
      group (50% versus 27%, p=0.04). At follow-up, patients with eBiPLEDs had more
      seizures than patients with ePLEDs (87.5% versus 61.3%). CONCLUSION: ePLEDs is
      associated with significant morbidity and mortality. However, the etiology of
      ePLEDs and brain dysfunction will influence the long-term outcome. This
      information is invaluable for prognostication and underscores the importance of
      rigorous management of patients with ePLEDs.

PMID- 22608975
TI  - Using Rasch measurement theory to assess three depression scales among adults
      with epilepsy.
AB  - People with chronic conditions, such as epilepsy, are at a high risk for
      depression; however depression is often under-recognized and undertreated.
      Depression scales, including one specific to people with epilepsy, have been used
      for screening in this population, although none have been assessed with Rasch
      measurement theory. This study used Rasch analyses in order to evaluate and
      compare the psychometric properties of the modified Beck Depression Inventory,
      the Patient Health Questionnaire, and the Neurological Disorders Depression
      Inventory for Epilepsy in a sample of people with epilepsy and depression who
      participated in an intervention designed to reduce depressive symptoms. A
      secondary purpose was to assess item functioning across time. The sample includes
      44 participants in the Project UPLIFT program who completed the assessments
      before and after taking part in the intervention. Results of the Rasch analysis
      indicate that the three depression scales functioned as intended. There was good
      overall targeting between the items and the sample, acceptable model-data fit,
      and good reliability of separation for persons, items, and time. The participants
      experienced a significant decrease in depressive symptoms from pretest to
      posttest. This study illustrates the value of using model-based measurement with
      the Rasch model to combine items across the three depression scales. It also
      demonstrates an approach for analyzing and evaluating the results of small scale
      intervention programs, such as the UPLIFT program.

PMID- 22608976
TI  - Trends in antiepileptic drug utilisation in UK primary care 1993-2008: cohort
      study using the General Practice Research Database.
AB  - PURPOSE: To describe changes in utilisation of antiepileptic drugs (AED) by
      people with epilepsy in the United Kingdom during 1993-2008. METHODS: Cohort
      study of 63,586 participants with epilepsy and prescribed AEDs from 434 UK family
      practices. Prescriptions for different AEDs and AED combinations were evaluated
      by calendar year, gender and age group. RESULTS: Total follow-up was 361,207
      person-years, with 282,080 person-years treated with AEDs and 79,126 person-years
      untreated. AED monotherapy accounted for 72.6% of treated person years of follow
      up. Carbamazepine and valproates were among the most commonly used medications
      throughout 1993-2008. Phenytoin accounted for 39.5% of treated person-years in
      1993 declining to 18.3% by 2008. Use of barbiturates declined from 14.3% in 1993
      to 6.0% in 2008. In contrast between 1993 and 2008 there were substantial
      increases in the use of lamotrigine (2.0% to 17.0%) and to a lesser extent
      levetiracetam (0% to 8.6%). Newer AEDs were more frequently prescribed to younger
      participants, especially women aged 15-44 years, while older adults were more
      likely to be prescribed longer established AEDs. In 1993, 201 different AED
      combinations were prescribed, increasing to 500 different combinations in 2008.
      Combinations of sodium valproate and carbamazepine were frequent throughout,
      while sodium valproate and lamotrigine was frequent in 2008. CONCLUSIONS:
      Utilisation of newer AEDs in UK primary care has increased between 1993 and 2008
      with increasing use of diverse combinations of AEDs. The data quantify exposure
      to AEDs relevant to planning analytical pharmaco-epidemiological studies, as well
      as providing information to inform prescribing policies.

PMID- 22608977
TI  - Translocation of 125I, 75Se and 36Cl to wheat edible parts following wet foliar
      contamination under field conditions.
AB  - Apart from radiocaesium and radiostrontium, there have been few studies on the
      foliar transfer of radionuclides in plants. Consequently, specific translocation
      factor (ftr) values for (129)I, (79)Se and (36)Cl are still missing from the IAEA
      reference databases. The translocation of short - lived isotopes, (125)I and
      (75)Se, and of (36)Cl to wheat grain were measured under field conditions
      following acute and chronic wet foliar contamination at various plant growth
      stages in the absence of leaching caused by rain. The translocation factors
      ranged from 0.02% to 1.1% for (125)I (a value similar to Sr), from 0.1% to 16.5%
      for (75)Se, and from 1% to 14.9% for (36)Cl. Both (36)Cl and (75)Se were as
      mobile as Cs. The phenomenological analysis showed that each element displayed a
      specific behavior. Iodide showed the lowest apparent mobility because of its
      preferential fixation in or on the leaves and a significant amount probably
      volatilized. Selenite internal transfer was significant and possibly utilized the
      sulphur metabolic pathway. However bio - methylation of selenite may have led to
      increased volatilization. Chloride was very mobile and quickly diffused
      throughout the plant. In addition, the analysis underlined the importance of
      plant growth responses to annual variations in weather conditions that can affect
      open field experiments because plant growth stage played a major role in ftr
      values dispersion. The chronic contamination results suggested that a series of
      acute contamination events had an additive effect on translocated elements. The
      highest translocation value obtained for an acute contamination event was shown
      to be a good conservative assessment of chronic contamination if data on chronic
      contamination translocation are lacking. The absence of rain leaching during the
      experiment meant that this investigation avoided potential radionuclide transfer
      by the roots, which also meant that radionuclide retention on or in the leaves
      was maximized. This study was therefore able to obtain accurate translocation
      factors, which are probably among the highest that could be recorded.

PMID- 22608978
TI  - [Misdiagnosed childhood sarcoidosis as non-Langerhans' cell histiocytosis treated
      with tumor necrosis factors-alpha antagonists].
AB  - Sarcoidosis is a chronic multisystemic granulomatous disease of unknown origin.
      Generalised eruptive histiocytosis is a rare, benign, self-healing, non
      Langerhans' cell histiocytosis (non-LCH). We report the case of an 8-year-old
      girl with sarcoidosis who was misdiagnosed as non-LCH. She was treated with oral
      corticosteroids, methotrexate and adalimumab, but there was insufficient control
      of ocular disease. The introduction of infliximab achieved a control of the
      uveitis and enabled the corticosteroid dose to be tapered. In some cases of
      sarcoidosis the lack of well-organised granuloma formation at the beginning of
      the disease, and the presence of prominent giant cells may suggest alternative
      diagnoses, such as non-LCH. Although the experience of tumour necrosis factor
      alpha antagonists use in children with sarcoidosis is limited, these drugs may be
      helpful for those patients experiencing a severe and refractory disease.

PMID- 22608979
TI  - [Bronchiolitis and convulsions: not always due to apnoeas].

PMID- 22608980
TI  - Semiconductor quantum dots for in vitro diagnostics and cellular imaging.
AB  - The need for companion diagnostics, point-of-care testing (POCT) and high
      throughput screening in clinical diagnostics and personalized medicine has pushed
      the need for more biological information from a single sample at extremely low
      concentrations and volumes. Optical biosensors based on semiconductor quantum
      dots (QDs) can answer these requirements because their unique photophysical
      properties are ideally suited for highly sensitive multiplexed detection. Many
      different biological systems have been successfully scrutinized with a large
      variety of QDs over the past decade but their future as widely applied commercial
      biosensors is still open. In this review, we highlight recent in vitro diagnostic
      and cellular imaging applications of QDs and discuss milestones and obstacles on
      their way toward integration into real-life diagnostic and medical applications.

PMID- 22608981
TI  - A review of X-ray explosives detection techniques for checked baggage.
AB  - In recent times, the security focus for civil aviation has shifted from hijacking
      in the 1980s, towards deliberate sabotage. X-ray imaging provides a major tool in
      checked baggage inspection, with various sensitive techniques being brought to
      bear in determining the form, and density of items within luggage as well as
      other material dependent parameters. This review first examines the various
      challenges to X-ray technology in securing a safe system of passenger
      transportation. An overview is then presented of the various conventional and
      less conventional approaches that are available to the airline industry, leading
      to developments in state-of-the-art imaging technology supported by enhanced
      machine and observer-based decision making principles.

PMID- 22608982
TI  - Radiation dose reduction in a neonatal intensive care unit in computed
      radiography.
AB  - The purpose of this study was to evaluate the dose received by chest x-rays in
      neonatal care with thermoluminescent dosimetry and to determine the level of
      exposure where the quantum noise level does not affect the diagnostic image
      quality in order to reduce the dose to neonates. In pediatric radiology,
      especially the prematurely born children are highly sensitive to the radiation
      because of the highly mitotic state of their cells; in general, the sensitivity
      of a tissue to radiation is directly proportional to its rate of proliferation.
      The sample consisted of 208 neonatal chest x-rays of 12 neonates admitted and
      treated in a Neonatal Intensive Care Unit (NICU). All the neonates were preterm
      in the range of 28-34 weeks, with a mean of 30.8 weeks. Entrance Surface Doses
      (ESD) values for chest x-rays are higher than the DRL of 50 MUGy proposed by the
      National Radiological Protection Board (NRPB). In order to reduce the dose to
      neonates, the optimum image quality was achieved by determining the level of ESD
      where level noise does not affect the diagnostic image quality. The optimum ESD
      was estimated for additional 20 chest x-rays increasing kVp and reducing mAs
      until quantum noise affects image quality.

PMID- 22608983
TI  - A comparison of protocols for external beam radiotherapy beam calibrations.
AB  - A number of codes of practice (CoP) for electron and photon radiotherapy beam
      dosimetry are currently in use. Comparison is made of the more widely used of
      these, specifically those of the International Atomic Energy Agency (IAEA TRS
      398), the American Association of Physicists in Medicine (AAPM TG-51) and the
      Institute of Physics and Engineering in Medicine (IPEM 2003). All are based on
      calibration of ionization chambers in terms of absorbed dose to water, each
      seeking to reduce uncertainty in delivered dose, providing an even stronger
      system of primary standards than previous air-kerma based approaches. They also
      provide a firm, traceable and straight-forward formalism (Radiology, 1996).
      Included in making dose assessments for the three CoP are calibration
      coefficients for a range of beam quality indices. Measurements have been
      performed using clinical photon and electron beams, the absorbed dose to water
      being obtained following the recommendations given by each code. Electron beam
      comparisons have been carried out using measurements for electron beams of
      nominal energies 6, 9, 12, 16 and 20 MeV. Comparisons were also carried out for
      photon beams of nominal energies 6 and 18 MV. For photon beams use was made of
      NE2571 cylindrical graphite walled ionization chambers, cross-calibrated against
      an NE2611 Secondary Standard; for electron beams, PTW Markus and NACP-02 plane
      parallel chambers were used. Irradiations were made using Varian 600C/2100C
      linacs, supported by water tanks and Virtual WaterTM phantoms. The absorbed doses
      for photon and electron beams obtained following these CoP are all in good
      agreement, with deviations of less than 2%. A number of studies have been carried
      out by different groups in different countries to examine the consistency of
      dosimetry codes of practice or protocols. The aim of these studies is to confirm
      that the goal of those codes is met, namely uniformity in establishment of
      dosimetry of all radiation beam types used in cancer therapy in the world, and
      this is one of the studies.

PMID- 22608984
TI  - Body image change in obese and overweight women enrolled in a weight-loss
      intervention: the importance of perceived versus actual physical changes.
AB  - Using the exercise and self-esteem model as a guiding framework, this study
      examined variables related to body image change among 88 overweight and obese
      women (M(age)=28.4+/-7.8; M(BMI)=31.6+/-3.5) participating in a 16-week diet and
      exercise weight-loss intervention. Measures of body image and potential
      mechanisms of body image change (actual and perceived physical changes, self
      efficacy) were administered at baseline, Weeks 8 and 16. Body image improved
      significantly over the study time-points (ps<.001). Perceived physical changes
      accounted for most explained variance (12-37%) in body image change (total
      R(2)(adj)=.21-.50). Improved perceptions of body fat were a particularly
      important predictor in each model (ps<=.04). Results support the notion that to
      improve body image, perceived changes to the body are more important than actual
      changes. Such information is integral to developing theories to explain body
      image change and interventions to maximize it.

PMID- 22608985
TI  - Mitochondrial dysfunction accounts for aldosterone-induced epithelial-to
      mesenchymal transition of renal proximal tubular epithelial cells.
AB  - Epithelial-mesenchymal transition (EMT) plays a pivotal role in the pathogenesis
      of renal tubulointerstitial fibrosis. We previously demonstrated that aldosterone
      (Aldo)-induced EMT is dependent on mitochondrial-derived oxidative stress. This
      study investigated whether mitochondrial dysfunction (MtD) is involved in the
      pathogenesis of EMT and whether peroxisome proliferator-activated receptor-gamma
      coactivator-1alpha (PGC-1alpha), a major regulator of oxidative metabolism and
      mitochondrial function, prevents EMT by improving MtD. Aldo decreased PGC-1alpha
      expression while increasing its acetylation and induced MtD, as evidenced by
      oxidative stress, mitochondrial membrane potential collapse, mitochondrial DNA
      damage, and mitochondrial complex activity reduction. Aldo time-dependently
      induced p66Shc phosphorylation and expression. Mineralocorticoid receptor
      antagonist eplerenone and p66Shc short interfering RNA prevented Aldo-induced MtD
      and EMT, as evidenced by downregulation of alpha-smooth muscle actin and
      upregulation of E-cadherin. Mitochondrial DNA depletion by ethidium bromide or
      mitochondrial transcription factor A inhibitory RNA (RNAi) induced MtD, further
      promoting EMT. RNAi-mediated suppression of PGC-1alpha induced MtD and EMT,
      whereas overexpression of PGC-1alpha prevented Aldo-induced MtD and inhibited
      EMT. Similarly, overexpression of silent mating type information regulation 2
      homolog 1 (SIRT1), a gene upstream of PGC-1alpha, or the SIRT1 activator
      resveratrol restored Aldo-induced MtD and EMT by upregulating PGC-1alpha. These
      findings, which implicate a role for MtD in EMT and suggest that SIRT1 and PGC
      1alpha coordinate to improve mitochondrial function and EMT, may guide us in
      therapeutic strategies for renal tubulointerstitial fibrosis.

PMID- 22608986
TI  - Initial management of septic patients with hyperglycemia in the noncritical care
      inpatient setting.
AB  - BACKGROUND: Previous research on the management of hyperglycemia in patients with
      sepsis has focused primarily on those with established organ failure in the
      critical care setting. The impact of hyperglycemia and glycemic control in
      patients with infection before developing severe sepsis or shock remains
      undefined. METHODS: This observational, prospective, cohort study investigated
      the relationship between initial 72-hour time-weighted mean glucose
      concentrations and in-hospital mortality, intensive care unit transfer, and
      hospital length of stay in a cohort of patients with an acute infection who were
      admitted from the emergency department to a non-intensive care unit hospital
      ward. We used multivariate regression models adjusted for age, diabetes, and
      disease severity. RESULTS: A total of 1849 patients were included, of whom 29%
      had diabetes. In the 1310 nondiabetic patients, we observed hyperglycemia using
      time-weighted glucose concentrations: 121 to 150 mg/dL (n=204, 16%), 151 to 180
      mg/dL (n=32, 2.4%), and greater than 180 mg/dL (n=21, 1.6%). Insulin treatment
      was infrequent in nondiabetic patients, with 9%, 13%, and 29% of nondiabetic
      patients in these ranges receiving insulin, respectively. As patient glucose
      values increased, in-hospital mortality increased in nondiabetic patients, with
      odds ratios (ORs) of 4.4 (95% confidence interval [CI], 1.8-11), 10.0 (95% CI,
      2.5-40), and 9.3 (95% CI, 1.9-44.0). Conversely, hyperglycemia did not confer an
      increased risk of adverse outcomes in diabetic patients. Likewise, increased risk
      for unplanned intensive care unit admission from the floor demonstrated ORs of
      2.2 (95% CI, 1.1-4.3), 2.0 (95% CI, 0.45-8.9), and 6.3 (95% CI, 1.9-20.6) in
      nondiabetic patients, whereas no increased risk was found in diabetic patients.
      CONCLUSIONS: In this cohort of acutely infected patients without established
      severe sepsis or shock, higher glucose concentrations within the first 72 hours
      in the nondiabetic population were associated with worse hospital outcomes and
      were less likely to be treated with insulin compared with diabetic patients.

PMID- 22608987
TI  - The Food and Drug Administration decision not to approve the 110 mg dose of
      dabigatran: give us a way out.

PMID- 22608988
TI  - The potential of forgiveness as a response for coping with negative peer
      experiences.
AB  - Coping strategies employed by adolescents in response to negative peer
      experiences are related to their adjustment. This study examines the potential of
      forgiveness as a coping response for negative peer experiences in early
      adolescence. Participants were 616 6th through 8th grade students at a middle
      school (46% girls) who completed self-report measures of bullying and
      victimization experiences, general coping strategies in response to bullying,
      social anxiety, self-esteem, and a measure of forgiveness to a self-identified
      experience of being bullied or hurt by a peer. Forgiveness was positively
      associated with conflict resolution, advice and support seeking strategies, and
      negatively associated with revenge seeking. Forgiveness was also positively
      associated with concurrent self-esteem and negatively associated with social
      anxiety. Further, forgiveness was related to social anxiety and self-esteem after
      accounting for bullying behavior and victimization experiences, general coping
      responses, and gender. Developmental considerations of forgiveness and
      implications for this response are considered.

PMID- 22608989
TI  - [Prevalence of atrial fibrillation in emergency departments].

PMID- 22608990
TI  - Surface characterization of dental Y-TZP ceramic after air abrasion treatment.
AB  - OBJECTIVE: The aim of this study was to characterize the surface of Y-TZP after
      abrasion with various airborne particles. METHODS: The Y-TZP blanks were cut into
      44 discs and sintered according to the manufacturer's instructions. The specimens
      were treated as follows: (a) control specimens, (b) abraded with 50MUm alumina,
      (c) abraded with 110MUm alumina, (d) abraded with 30MUm silica-coated alumina,
      (e) abraded with 110MUm silica-coated alumina, (f) abraded with 110MUm alumina
      followed by 110MUm silica-coated alumina particles. Airborne abrasion was
      performed at a pressure of 2.5bar for 15s/cm(2). The Y-TZP was characterized
      using X-ray photoelectron spectroscopy (XPS), field emission scanning electron
      microscopy (FESEM) and X-ray diffraction analysis (XRD). RESULTS: Surface
      morphology of Y-TZP ceramic was changed after the airborne abrasion process
      compared to the control specimens. The grain boundaries disappeared and part of
      the airborne particles are embedded and/or rested on the ceramic surfaces. The
      elemental composition of the Y-TZP surface after the airborne abrasion process
      depended on the type and size of these particles. The concentration of Si
      resulted higher after the airborne abrasion process with 110MUm alumina followed
      by 110MUm silica-coated alumina particles in comparison to the specimens abraded
      with 110MUm silica-coated alumina particles. The ratio of elements normalized by
      yttrium for these specimens was: [Zr]/[Y]/[Al]/[Si]=15.2/1.0/26.0/73.6,
      respectively. CONCLUSION: The change of grain topography occurred during each
      impact process. Silica nano-particles covered not only loosely the abraded
      ceramic surface after abrasion process, but the release of kinetic energy in form
      of thermal energy resulted in melting of the ceramic surface and in the formation
      of zirconium silicate.

PMID- 22608992
TI  - Biosynthesis of high molecular weight hyaluronic acid by Streptococcus
      zooepidemicus using oxygen vector and optimum impeller tip speed.
AB  - The potential use of n-dodecane and n-hexadecane as oxygen vectors for enhancing
      hyaluronic acid (HA) biosynthesis by Streptococcus zooepidemicus ATCC 39920 was
      investigated using a 2-L stirred-tank bioreactor equipped with helical ribbon or
      Rushton turbine impellers. The volumetric fraction of the oxygen vector
      influenced the gas-liquid volumetric oxygen transfer coefficient (K(L)a)
      positively. Batch HA fermentation with 1% (v/v) n-dodecane or 0.5% (v/v) n
      hexadecane addition was carried out at different impeller tip speeds. Even though
      cell growth was lower in the fermentation with oxygen vector addition, the HA
      productivity and molecular weight were higher when compared to the fermentation
      without oxygen vector at low impeller tip speed. The highest HA concentration
      (4.25 gHA/l) and molecular weight (1.54 * 10(7) Da) were obtained when 0.5% (v/v)
      n-hexadecane and 0.785 m/s impeller tip speed of helical ribbon were used.

PMID- 22608991
TI  - Autophagy proteins in macroendocytic engulfment.
AB  - Eukaryotic cells must constantly degrade both intracellular and extracellular
      material to maintain cellular and organismal homeostasis. Two engulfment
      pathways, autophagy and phagocytosis, contribute to the turnover of intracellular
      and extracellular substrates by delivering material to the lysosome. Historically
      these are thought to be separate pathways, but recent studies have revealed the
      direct participation of autophagy proteins in phagocytosis. Autophagy proteins
      lipidate LC3 onto phagosomes and other macroendocytic vacuole membranes, and are
      required for lysosomal degradation of engulfed cargo, demonstrating an
      autophagosome-independent role for autophagy proteins in mediating the turnover
      of extracellular substrates. This review discusses the biological systems in
      which autophagy proteins have been found to regulate lysosome fusion to non
      autophagic membranes.

PMID- 22608993
TI  - Metabolite profiling of soy sauce using gas chromatography with time-of-flight
      mass spectrometry and analysis of correlation with quantitative descriptive
      analysis.
AB  - Soy sauces, produced from different ingredients and brewing processes, have
      variations in components and quality. Therefore, it is extremely important to
      comprehend the relationship between components and the sensory attributes of soy
      sauces. The current study sought to perform metabolite profiling in order to
      devise a method of assessing the attributes of soy sauces. Quantitative
      descriptive analysis (QDA) data for 24 soy sauce samples were obtained from well
      selected sensory panelists. Metabolite profiles primarily concerning low
      molecular-weight hydrophilic components were based on gas chromatography with
      time-of-flightmass spectrometry (GC/TOFMS). QDA data for soy sauces were
      accurately predicted by projection to latent structure (PLS), with metabolite
      profiles serving as explanatory variables and QDA data set serving as a response
      variable. Moreover, analysis of correlation between matrices of metabolite
      profiles and QDA data indicated contributing compounds that were highly
      correlated with QDA data. Especially, it was indicated that sugars are important
      components of the tastes of soy sauces. This new approach which combines
      metabolite profiling with QDA is applicable to analysis of sensory attributes of
      food as a result of the complex interaction between its components. This approach
      is effective to search important compounds that contribute to the attributes.

PMID- 22608994
TI  - Functional and heterologous expression of human protein O-linked mannose beta-1,2
      N-acetylglucosaminyltransferase 1 in zebrafish.
AB  - Although membrane-associated proteins are related to many diseases and are
      important targets for drug discovery, their expression is often difficult in
      bacterial hosts such as Escherichia coli. To overcome this limitation, here, we
      focused on a novel host-vector system in zebrafish for the expression of human
      protein O-linked mannose beta-1,2-N-acetylglucosaminyltransferase 1 (hPOMGnT1)
      which is related to muscle-eye-brain disease. For the expression of hPOMGnT1, the
      vector pZex-EGFP-pXI-hPOMGnT1 was constructed and injected into fertilized eggs.
      Using this system, we demonstrated that recombinant hPOMGnT1 was successfully
      expressed in the whole bodies of zebrafish embryos.

PMID- 22608995
TI  - High-temperature ethanol fermentation by immobilized coculture of Kluyveromyces
      marxianus and Saccharomyces cerevisiae.
AB  - Suspended and immobilized cocultures of the thermotolerant yeast, Kluyveromyces
      marxianus DMKU 3-1042 and the mesophilic flocculent yeast, Saccharomyces
      cerevisiae M30 were studied for their abilities to improve production and
      stability of ethanol fermentation. Sugarcane juice and blackstrap molasses, at
      initial sugar concentrations of 220 g/L, were used as carbon sources. The results
      indicated that the coculture system could improve ethanol production from both
      sugarcane juice and blackstrap molasses when the operating temperature ranged
      between 33  degrees C and 45  degrees C. High temperature tolerances were
      achieved when the coculture was immobilized. The immobilized coculture was more
      effective in high-temperature ethanol fermentation than the suspended cultures.
      The coculture immobilized on thin-shell silk cocoon and fermented at 37  degrees
      C and 40  degrees C generated maximal ethanol concentrations of 81.4 and 77.3
      g/L, respectively, which were 5.9-8.7% and 16.8-39.0% higher than those of the
      suspended cultures, respectively.

PMID- 22608996
TI  - Protecting a serial killer: pathways for perforin trafficking and self-defence
      ensure sequential target cell death.
AB  - Considerable progress has been made in understanding how cytotoxic lymphocytes
      use the highly toxic pore-forming protein perforin to eliminate dangerous cells,
      while remaining refractory to lysis. At least two mechanisms jointly preserve the
      killer cell: the C-terminal residues of perforin dictate its rapid export from
      the endoplasmic reticulum (ER), whose milieu otherwise favours pore formation;
      perforin is then stored in secretory granules whose acidity prevent its
      oligomerisation. Following exocytosis, perforin delivers the proapoptotic
      protease, granzyme B, into the target cell by disrupting its plasma membrane.
      Although the precise mechanism of perforin/granzyme synergy remains
      controversial, the recently defined crystal structure of the perforin monomer and
      cryo-electron microscopy (EM) of the entire pore suggest that passive
      transmembrane granzyme diffusion is the dominant proapoptotic mechanism.

PMID- 22608997
TI  - Atrial fibrillation: an inflammatory disease or a conformational disorder?

PMID- 22608998
TI  - Closed antegrade intramedullary pinning for reduction and fixation of metatarsal
      fractures.
AB  - The purpose of this study was to present the results of the metatarsal fractures
      treated with a closed antegrade intramedullary pinning technique. The records of
      35 consecutive patients with metatarsal fractures operated on from August 2005 to
      June 2010 by the authors were retrospectively reviewed. Four patients were not
      contactable and 1 patient refused to participate. Accordingly, the study cohort
      was composed of 30 patients (24 male, 6 female) with 46 metatarsal head, neck, or
      shaft fractures. Inclusion criteria were metatarsal head, neck, or shaft
      fractures with a displacement of more than 3 to 4 mm or an angulation of more
      than 10 degrees  in the sagittal plane. Fractures combined with Lisfranc injury
      or metatarsal base fractures were excluded, as were bicortical comminuted
      fractures or long oblique fractures. Times to bone union, limitations of motion
      at affected metatarsophalangeal joints, and residual pain were evaluated at 6
      weeks after surgery and at final follow-up. American Orthropedic Foot and Ankle
      Society scale was evaluated at final follow-up. Fracture union was obtained at an
      average of 7.1 (range 6 to 10) weeks. Two patients had moderate limitation of
      metatarsophalangeal joint at 6 weeks but recovered to full range at final follow
      up. Average American Orthropedic Foot and Ankle Society score at final follow-up
      was 96.7 (range 83 to 100) points. Closed antegrade intramedullary pinning was
      found to be a useful method for treating displaced metatarsal fractures and to
      allow immediate joint motion and partial weightbearing in a stiff-soled shoe.

PMID- 22608999
TI  - Plantar heel reconstruction with a sensate plantar medial artery musculocutaneous
      pedicled island flap after wide excision of melanoma.
AB  - Reconstruction of soft tissue defects in the plantar heel pad presents a surgical
      challenge that requires replacing the lost tissue with another tissue having
      similarly unique physical characteristics. This case report describes a
      reconstruction of the plantar heel pad after wide excision of a heel melanoma,
      using a sensate plantar medial artery musculocutaneous pedicled island flap.

PMID- 22609000
TI  - Clinical Saccharomyces cerevisiae isolates cannot cross the epithelial barrier in
      vitro.
AB  - Saccharomyces cerevisiae is generally considered to be a safe organism and is
      essential to produce many different kinds of foods as well as being widely used
      as a dietary supplement. However, several isolates, which are genetically related
      to brewing and baking yeasts, have shown virulent traits, being able to produce
      human infections in immunodeficient patients. Previously it has been shown that
      the administration of S. cerevisiae clinical isolates can lead to systemic
      infections, reaching several organs in murine systems. In this work, we studied
      S. cerevisiae clinical isolates in an in vitro intestinal epithelial barrier
      model, comparing their behaviour with that of several strains of the related
      pathogens Candida glabrata and Candida albicans. The results showed that, in
      contrast to C. glabrata and C. albicans, S. cerevisiae was not able to cross the
      intestinal barrier. We concluded that S. cerevisiae can only perform
      opportunistic or passive crossings when epithelial barrier integrity is
      previously compromised.

PMID- 22609001
TI  - Ipsilateral second nasolabial flap reconstruction for oral squamous cell
      carcinoma.

PMID- 22609002
TI  - Evaluation of hand function in rheumatic disease. Validation and usefulness of
      the Spanish version AUSCAN, m-SACRAH and Cochin questionnaires.
AB  - INTRODUCTION: Questionnaires to evaluate hand function are variable in the number
      of items, domains and diseases in which they had been previously used.
      OBJECTIVES: a) To translate to Spanish and validate the m-SACRAH and AUSCAN
      questionnaires; b) to do a transcultural adaptation of DASHe, previously
      validated in Spain), and c) to compare them and the Cochin questionnaire
      (previously validated in Mexico), in rheumatic patients with variable impairment
      of hand function. MATERIAL AND METHODS: m-SACRAH, AUSCAN and DASH were
      translated/retro-translated and adapted. The final version was revised to
      determine content validity and them, plus Cochin were applied to 10 healthy
      subjects (pilot study) with a variable educational level and in 16 rheumatic
      patients with variable diagnoses and degrees of hand function impairment; all
      patients answered 4 questionnaires and were evaluated clinically by blinded
      investigators. RESULTS: Seventy six percent were women, mean age 45.7+/-11.4
      years. Cronbachs alpha >0.90; time to answer went from 2.3+/-0.087 (AUSCAN) to
      3.5+/-0.36 minutes (DASH). There was good correlation among them (r=0.0683 AUSCAN
      m-SACRAH to r=0.889 AUSCAN-DASH) and good capability for discrimination between
      patients with mild VS moderate to severe impairment was also demonstrated;
      patients with mild impairment needed less time to answer them and there were no
      significant differences among questionnaire scores. Patients prefered AUSCAN
      (10/16), Cochin (4/16) and m-SACRAH (2/16). CONCLUSION: The 4 questionnaires are
      useful to evaluate hand function in rheumatic patients and have good
      discrimination capability. More patients preferred AUSCAN.

PMID- 22609003
TI  - Tobacco and other environmental risk factors in rheumatoid arthritis.
AB  - Many environmental factors have been associated with an increased risk of
      developing Rheumatoid Arthritis (RA), but so far smoking is the only
      environmental risk factor that has been extensively studied and widely accepted.
      Smoking is associated with an increased risk of developing seropositive RA (RF
      and/or ACPA). Recent studies show that tobacco smoking can influence disease
      phenotype, with the development of more aggressive disease and greater joint
      damage; but other studies show contradictory results. Recent data suggests that
      response to antirheumatic therapy in RA is worse in smokers. In this article we
      review different environmental factors that have been associated with an
      increased risk of developing RA, with a special interest in tobacco smoking.

PMID- 22609004
TI  - Drug prescription strategies in the treatment of patients with fibromyalgia.
AB  - OBJECTIVE: To analyze prescription strategies followed by rheumatologist
      specialized in FM treatment. METHODS: A prospective, multicentric, 3-month follow
      up study with two visits. The drug treatment was started following usual clinical
      practice conditions. Prescription of benzodiazepines, hypnotics, anticonvulsants
      and antidepressants were those mainly studied. Clinical evaluation was performed
      by the ICAF (Combined index of affection in patients with fibromyalgia)
      questionnaire. The most frequent strategies and their size effect were
      calculated. RESULTS: A total of 232 patients attending 15 rheumatology centers
      were included. The introduction of an anticonvulsant or an antidepressant were
      the most common drug strategies followed in 17.7% and 14.7% of patients,
      respectively. Both strategies produced a statistically significant clinical
      improvement. The most effective strategy (with an effect size of nearly 1) was
      the introduction of both drugs (6.5% patients), which increased the
      antidepressants effect size in 50% and 100% for anticonvulsants. The strategy of
      no change in the number of drug prescriptions was the most frequent (35.8%
      patients) but no significant clinical improvement was found in these patients.
      Some other strategies were very uncommon and have not been analyzed in this
      study. CONCLUSION: The introduction of anticonvulsants or antidepressants, in an
      isolated or combined form, produces a significant clinical improvement in FM
      patients. The most effective drug strategy is the introduction of both drugs at
      the same time. The least effective strategy is not to change the number of drug
      prescriptions.

PMID- 22609005
TI  - High plasma thiocyanate levels modulate protein damage induced by myeloperoxidase
      and perturb measurement of 3-chlorotyrosine.
AB  - Smokers have an elevated risk of atherosclerosis but the origin of this elevated
      risk is incompletely defined, though increasing evidence supports a role for the
      oxidant-generating enzyme myeloperoxidase (MPO). In previous studies we have
      demonstrated that smokers have elevated levels of thiocyanate ions (SCN(-)),
      relative to nonsmokers, and increased thiol oxidation, as SCN(-) is a favored
      substrate for MPO, and the resulting hypothiocyanous acid (HOSCN) targets thiol
      groups rapidly and selectively. In this study we show that increased HOSCN
      formation by MPO diminishes damage to nonthiol targets on both model proteins and
      human plasma proteins. Thus high SCN(-) levels protect against HOCl- and MPO
      mediated damage to methionine, tryptophan, lysine, histidine, and tyrosine
      residues on proteins. Furthermore, levels of the HOCl-mediated marker compound 3
      chlorotyrosine and the cross-linked product dityrosine are decreased. Plasma
      protein 3-chlorotyrosine levels induced by HOCl exposure in nonsmokers are
      elevated over the levels detected in smokers when exposed to identical oxidative
      insult (P<0.05), and a strong inverse correlation exists between plasma SCN(-)
      levels and 3-chlorotyrosine concentrations (r=0.6182; P<0.0001). These
      correlations were also significant for smokers (r=0.2724; P<0.05) and nonsmokers
      (r=0.4141; P<0.01) when analyzed as individual groups. These data indicate that
      plasma SCN(-) levels are a key determinant of the extent and type of protein
      oxidation induced by MPO on isolated and plasma proteins and that smoking status
      and resulting high SCN(-) levels can markedly modulate the levels of the widely
      used biomarker compound 3-chlorotyrosine.

PMID- 22609006
TI  - Functional dissection of Nrf2-dependent phase II genes in vascular inflammation
      and endotoxic injury using Keap1 siRNA.
AB  - Keap1 is a cytoplasmic repressor of the transcription factor Nrf2, and its
      degradation induces Nrf2 activation, leading to upregulation of antioxidant phase
      II genes. We investigated the roles of phase II genes in vascular inflammation
      and septic injury using Keap1 siRNA and elucidated its underlying mechanism.
      Selective knockdown of Keap1 with siRNA promoted Nrf2-dependent expression of
      phase II genes in endothelial cells, such as heme oxygenase-1 (HO-1), glutamate
      cysteine ligase (GCL), and peroxiredoxin-1 (Prx1), resulting in the elevation of
      cellular glutathione levels and suppression of tumor necrosis factor (TNF)-alpha
      induced intracellular H(2)O(2) accumulation. Keap1 knockdown inhibited TNF-alpha
      induced expression of intracellular adhesion molecule-1 (ICAM-1) and vascular
      cell adhesion molecule-1 (VCAM-1) by suppressing NF-kappaB activation via
      inhibition of its upstream modulators, Akt, NIK, and IKK, resulting in the
      elevation of monocyte adhesion to endothelial cells. Importantly, these events
      were reversed by HO-1 and GCL inhibitors and Prx1-specific siRNA. Keap1 knockdown
      also inhibited endotoxin-induced expression of inducible nitric oxide synthase
      (iNOS) and TNF-alpha by upregulating HO-1, GCL, and Prx1 expression in
      macrophages. Moreover, in vivo Keap1 knockdown increased the expression of phase
      II genes and suppressed the expression of ICAM-1, VCAM-1, iNOS, and TNF-alpha in
      an endotoxemic mouse model, resulting in significant protection against liver and
      lung injuries and lethality. Our results indicate that Keap1 knockdown prevents
      NF-kappaB-mediated vascular inflammation and endotoxic shock by suppressing NF
      kappaB-mediated inflammatory gene expression via upregulation of Nrf2-mediated
      antioxidant genes. Thus, siRNA targeting Keap1 may provide a new therapeutic
      approach for inflammation-associated vascular diseases and sepsis.

PMID- 22609007
TI  - n Species impulsive migration model with Markovian switching.
AB  - An n species stochastic impulsive migration Lotka-Volterra model with Markovian
      switching in N different patches is presented and studied in this paper. By
      constructing appropriate Lyapunov functions, some sufficient conditions on the
      global positivity, the ultimate boundedness in mean and the extinction in mean
      are established. Real world examples are provided to illustrate the validity of
      our results. A discussion is given in the end.

PMID- 22609008
TI  - "Pulmonary edema induced by scorpion venom: evidence of cardiogenic nature".

PMID- 22609009
TI  - The type of atrial fibrillation is associated with long-term outcome in patients
      with acute ischemic stroke.
AB  - BACKGROUND/OBJECTIVES: We aimed to investigate the association between the type
      of atrial fibrillation (AF) and long-term outcome in terms of mortality and
      stroke recurrence in patients with ischemic stroke and non-valvular AF. METHODS:
      All consecutive patients admitted with acute ischemic stroke to Alexandra
      Hospital between 1993 and 2010 were included in the analysis. Patients were
      categorized in 3 groups according to the type of AF (paroxysmal, persistent, and
      permanent) and were followed up for up to 10 years after the index stroke or
      until death. The endpoints were inhospital, 30-day and 10-year stroke recurrence,
      and 30-day and 10-year all-cause mortality. The Kaplan-Meier product limit method
      was used to estimate the probability of 10-year stroke recurrence and survival.
      Multivariate Cox proportional hazard models were used to identify significant
      predictors of stroke recurrence and all-cause mortality. RESULTS: There were 811
      patients (419 females, 392 males) with non-valvular AF and mean age of 75.8 +/-
      9.4 years. 277 (34.2%) patients had paroxysmal AF, 165 (20.3%) persistent and 369
      (45.5%) permanent. Inhospital stroke recurrence rate was low (1.8%) and similar
      among the 3 patient groups; on the contrary, the probability of 10-year stroke
      recurrence was significantly higher in patients with permanent AF (p<0.01 by log
      rank test). The probability of 10-year survival was significantly higher in
      patients with paroxysmal AF (p<0.001 by log-rank test). The type of AF was a
      significant predictor of 10-year stroke recurrence and mortality. Patients with
      permanent AF had higher risk of stroke recurrence (HR: 1.78, 95%CI: 1.21-2.61)
      and mortality (HR: 1.55, 95%CI: 1.20-1.99) compared to patients with paroxysmal
      AF. CONCLUSIONS: Long-term outcome in stroke patients with AF is associated with
      the type of AF; patients with paroxysmal AF have lower rates of stroke recurrence
      and mortality.

PMID- 22609010
TI  - Uptake of pandemic influenza (H1N1)-2009 vaccines in Brazil, 2010.
AB  - In 2010, the Brazilian Ministry of Health organized a mass vaccination campaign
      of selected priority groups in response to the 2009 H1N1 influenza pandemic. The
      campaign was conducted in six phases from March to July, 2010. Priority groups
      included healthcare professionals, indigenous persons, pregnant women, young
      children, persons with chronic illnesses and otherwise healthy adults 20-39 years
      of age. Over 89 million doses of pandemic influenza vaccines were administered,
      surpassing immunization targets among several priority groups, including
      healthcare professionals. We reviewed strategies used in Brazil to promote
      vaccination against pandemic influenza as well as factors external to the
      campaign that may have contributed to vaccine uptake among priority groups.

PMID- 22609011
TI  - Early-life and contemporaneous nutritional and environmental predictors of
      antibody response to vaccination in young Gambian adults.
AB  - Recent research links nutritional exposures early in life with alterations in
      functional immunity that persist beyond childhood. Here we investigate predictors
      of antibody response to polysaccharide vaccines in a cohort of Gambian adults
      with detailed records from birth and early infancy available. 320 adults were
      given a single dose of a Vi polysaccharide vaccine for Salmonella typhi and a 23
      valent capsular polysaccharide pneumococcal vaccine. Anti-Vi antibody levels and
      antibodies against 4 pneumococcal serotypes (1, 5, 14 and 23F) were measured in
      serum samples collected at baseline and then 14 days following vaccination and
      compared to data available from birth and early infancy. Post-vaccination
      antibody titres to serotype 14 of the pneumococcal vaccine were negatively
      associated with rate of growth from birth to three months of age, infant weight
      at 12 months of age and season of birth, but no other associations were observed
      with early-life exposures. The strongest predictor of antibody levels was pre
      vaccination antibody titres, with adult height and serum neopterin levels at time
      of vaccination also implicated. The current study does not support the hypothesis
      that nutritional exposures early in life consistently compromise antibody
      response to polysaccharide vaccines administered in young adulthood.

PMID- 22609012
TI  - Effects of immunizing school children with 2009 influenza A (H1N1) monovalent
      vaccine on absenteeism among students and teachers in Maine.
AB  - The overall and indirect effects of immunizing school children with influenza A
      (H1N1) 2009 pandemic virus vaccine prior to and during the peak of virus
      circulation were evaluated on student and teacher school absenteeism. We used
      records collected from late 2009 through early 2010 from schools in four Maine
      counties. Mixed logistic regression models were used to estimate the daily
      association between school-level immunization coverage and absenteeism by level
      of influenza activity, after adjusting for the proportion of students receiving
      reduced-cost lunches, student minority status, absences adjacent to weekends and
      Thanksgiving, rural school location, and the circulation of other respiratory
      viruses. Increasing student immunization coverage was associated with reduced
      absenteeism during periods of high influenza activity. For example, as
      immunization coverage during the peak week of pandemic virus circulation
      increased from 38% to 69% (the 10th and 90th percentiles of observed coverage,
      respectively), relative reductions in daily absenteeism among all students,
      unimmunized students, and teachers were 8.2% (95% confidence interval [CI]: 6.5,
      9.9), 5.7% (95% CI: 4.2, 7.3), and 8.7% (95% CI: 1.3, 16), respectively.
      Increased vaccination coverage among school-aged Maine children had modest
      overall and indirect effects on student and teacher absenteeism, despite
      vaccination occurring just prior and during peak pandemic virus circulation.

PMID- 22609013
TI  - Age- and gender-specific effects on NRAMP1 gene polymorphisms and risk of the
      development of active tuberculosis in Tunisian populations.
AB  - BACKGROUND: Studies that have assessed NRAMP1 polymorphisms and their association
      with susceptibility to tuberculosis (TB) in humans have yielded conflicting
      results. In this study, we evaluated the association between NRAMP1 gene
      polymorphisms and the risk of the development of active TB in Tunisian
      populations. METHODS: The distribution of 3'-UTR and D543N polymorphisms in 223
      TB patients (168 patients with pulmonary TB (PTB) and 55 patients with
      extrapulmonary TB (EPTB)) and 150 healthy donors was determined by PCR
      restriction fragment length polymorphism (RFLP) method. RESULTS: We found that AA
      and AG genotypes appeared to be associated with susceptibility to PTB (odds ratio
      (OR) 10.8, 95% confidence interval (CI) 1.37-230.8; p corrected for the number of
      genotypes (pc)=0.018) and EPTB (OR 4.37, 95% CI 1.64-11.82; pc=0.0024),
      respectively, in patients aged less than 30 years. However, wild-type GG genotype
      appeared to be associated with resistance against PTB in females (OR 0.1, 95% CI
      0.01-0.74; pc=0.03). The 3'-UTR del/del genotype appeared to be associated with
      susceptibility to PTB in patients aged less than 30 years (OR 3.75, 95% CI 1.5
      9.52; pc=0.003). In contrast, TGTG+/del might be associated with resistance
      against the development of active PTB (OR 0.23, 95% CI 0.08-0.65; pc=0.003). A
      del haplotype appeared to be associated with susceptibility to PTB (OR 1.79, 95%
      CI 1.11-2.9; pc=0.04). CONCLUSIONS: Collectively, our results suggest an
      association of NRAMP1 3'-UTR and D543N polymorphisms with susceptibility to
      mycobacterial infection in Tunisian populations in relation to age and sex.

PMID- 22609014
TI  - Circulating nucleosomes as a predictor of sepsis and organ dysfunction in
      critically ill patients.
AB  - OBJECTIVES: Sepsis is a leading cause of death in critically ill patients, and
      apoptosis plays a major role in the pathophysiology of sepsis. Elevated levels of
      circulating nucleosomes released by apoptotic cells have been detected in
      patients with severe sepsis and septic shock. The aim of this study was to
      evaluate the diagnostic/prognostic value of circulating nucleosomes in sepsis.
      METHODS: Seventy-four newly admitted patients with an estimated length of stay in
      the intensive care unit of more than 48 h, were prospectively enrolled as cohort
      1. The second independent cohort (cohort 2) consisted of 91 post-surgery
      patients. Patients receiving chemotherapy, those with AIDS, those on steroid
      treatment, and those undergoing transplants were excluded. Levels of circulating
      nucleosomes within 24h of admission in both cohorts, and for cohort 1 also on
      days 3, 5, and 7 and a last time-point of ICU discharge or at imminent death,
      were measured and analyzed for their capacity to predict sepsis. The severity of
      the inflammatory response and organ dysfunction were assessed by cytokine levels
      and sepsis scores. RESULTS: Nucleosome levels on admission in septic patients
      were significantly higher than those in non-septic controls in both of the
      cohorts. The area under the receiver operating characteristic curve for admission
      nucleosome levels to differentiate septic patients from non-septic patients was
      0.70 (95% confidence interval (CI) 0.51-0.88) in cohort 1, 0.66 (95% CI 0.55
      0.79) in cohort 2, and 0.67 (95% CI 0.55-0.79) in all of the subjects. After
      multiple logistic regression analysis, circulating nucleosomes remained as an
      independent predictor of sepsis. Furthermore, the levels of circulating
      nucleosomes on admission were significantly correlated with the inflammatory
      response and organ dysfunction in sepsis. Meanwhile, a trend was observed for
      admission levels of circulating nucleosomes in non-survivors to be higher than
      those in survivors. CONCLUSIONS: The level of circulating nucleosomes in the
      serum has a predictive value for sepsis and organ dysfunction and may serve as a
      candidate biomarker for the diagnosis/prognosis of sepsis. Further studies are
      warranted to confirm the present findings.

PMID- 22609015
TI  - HEXIM1-binding elements on mRNAs identified through transcriptomic SELEX and
      computational screening.
AB  - The positive transcription elongation factor b (P-TEFb) is one of the main
      regulatory factors of the transcription mediated by RNA polymerase II (RNAPII). P
      TEFb promotes transcriptional elongation by phosphorylating its targets, which
      include the C-terminal domain of RNAPII. The activity of P-TEFb is negatively
      regulated by an RNA-binding protein HEXIM1 in association with 7SK snRNA. To
      search for other cellular RNAs that bind to HEXIM1, we used systematic evolution
      of ligands by exponential enrichment (SELEX) with the HeLa cDNA library as the
      initial pool source. We identified cad mRNA as a HEXIM1-binding RNA and confirmed
      their association in HeLa cells. In vitro mutational analysis showed that cad
      mRNA binds to HEXIM1 through its bulged stem structure located in exon 11. In
      addition, a computational search revealed other RNAs with similar stem
      structures, including brd4 and tcf3 mRNAs, both of which were shown to be
      coimmunoprecipitable with anti-HEXIM1 antibody in HeLa cells. Our findings
      suggest a possible role for HEXIM1 in the regulation of specific gene
      expressions.

PMID- 22609016
TI  - Kidins220/ARMS interacts with Pdzrn3, a protein containing multiple binding
      domains.
AB  - We report the identification of a novel partner of Kidins220/ARMS (Kinase D
      interacting substrate of 220 kDa/Ankyrin Repeat-rich Membrane Spanning) an
      adaptor of neurotrophin receptors playing crucial roles during neurogenesis.
      Screening a phage display library of brain cDNA products we found that D. rerio
      Pdzrn3, a protein containing RING-finger and PDZ-domains, interacts with
      Kidins220/ARMS through its first PDZ-domain. Both zebrafish proteins share high
      homology with the corresponding mammalian proteins and both genes are
      developmentally expressed in neural districts where early neurogenesis occurs.
      The interaction was also confirmed by biochemical assays and by co-localization
      at the tips of growing neurites of PC12 cells induced with nerve growth factor.

PMID- 22609017
TI  - Obstetrician-gynecologists, religious institutions, and conflicts regarding
      patient-care policies.
AB  - OBJECTIVE: The purpose of this study was to assess how common it is for
      obstetrician-gynecologists who work in religiously affiliated hospitals or
      practices to experience conflict with those institutions over religiously based
      policies for patient care and to identify the proportion of obstetrician
      gynecologists who report that their hospitals restrict their options for the
      treatment of ectopic pregnancy. STUDY DESIGN: We mailed a survey to a nationally
      representative sample of 1800 practicing obstetrician-gynecologists. RESULTS: The
      response rate was 66%. Among obstetrician-gynecologists who practice in
      religiously affiliated institutions, 37% have had a conflict with their
      institution over religiously based policies. These conflicts are most common in
      Catholic institutions (52%; adjusted odds ratio, 8.7; 95% confidence interval,
      1.7-46.2). Few reported that their options for treating ectopic pregnancy are
      limited by their hospitals (2.5% at non-Catholic institutions vs 5.5% at Catholic
      institutions; P = .07). CONCLUSION: Many obstetrician-gynecologists who practice
      in religiously affiliated institutions have had conflicts over religiously based
      policies. The effects of these conflicts on patient care and outcomes are an
      important area for future research.

PMID- 22609019
TI  - Prevalence of iron deficiency at the first age of the infants hospitalized in
      neonatal period.
AB  - Iron deficiency (ID) is a global health problem. We aimed to determine the
      prevalence of ID at the first year of life in infants who were hospitalized in
      our neonatal intensive care unit (NICU) and investigate the effects of various
      factors on iron status. One year follow-up data of 219 infants who were
      discharged from NICU was retrospectively evaluated. ID anemia and ID without
      anemia were detected in fifteen infants (6.8%) and five (2.3%) infants,
      respectively. We concluded that, due to prophylactic iron treatment and close
      follow-up, hospitalization in neonatal period did not have any adverse effect on
      iron status at first year of life.

PMID- 22609020
TI  - Restless legs syndrome in Czech patients with multiple sclerosis: an
      epidemiological and genetic study.
AB  - BACKGROUND: Restless legs syndrome (RLS) is a frequent neurological disorder
      which is presented in idiopathic and secondary form. Idiopathic RLS is associated
      with common genetic variants in four chromosomal regions. Recently, multiple
      sclerosis (MS) was identified as a common cause for secondary RLS. The aim of our
      study was to evaluate the prevalence of RLS among Czech patients with MS and to
      further analyze the impact of known genetic risk factors for RLS in patients with
      MS. METHODS: Each patient underwent a semi-structured interview. A patient was
      considered to be affected by RLS if all four standard criteria had ever been met
      in their lifetime. The sample was genotyped using 12 single nucleotide
      polymorphisms within the four genomic regions, which were selected according to
      the results of previous genome-wide association studies. RESULTS: A total of 765
      subjects with MS were included in the study and the diagnosis of RLS was
      confirmed in 245 subjects (32.1%, 95%CI 28.7-35.4%). The genetic association
      study included 642 subjects; 203 MS patients with RLS were compared to 438 MS
      patients without RLS. No significant association with MEIS 1, BTBD9, and PTPRD
      gene variants was found despite sufficient statistical power for the first two
      loci. There was a trend for association with the MAP2K5/SCOR1 gene - the best
      model for the risk allele was the recessive one (p nominal=0.0029, p corrected
      for four loci and two models=0.023, odds ratio=1.60). CONCLUSION: We confirmed
      that RLS prevalence was high in patients with multiple sclerosis, but this form
      did not share all genetic risk variants with idiopathic RLS.

PMID- 22609018
TI  - Maternal BMI, glucose tolerance, and adverse pregnancy outcomes.
AB  - OBJECTIVE: The purpose of this study was to estimate the association of pregravid
      body mass index (BMI), independent of 3-hour oral glucose tolerance test (OGTT)
      results, with pregnancy outcome. STUDY DESIGN: In this secondary analysis of a
      cohort of women with untreated mild gestational glucose intolerance, which was
      defined as a 50-g glucose loading test between 135 and 199 mg/dL and fasting
      glucose level of <95 mg/dL, we modeled the association between pregravid BMI,
      OGTT results, and both pregnancy complications and neonatal adiposity. RESULTS:
      Among 1250 participants, both pregravid BMI and glucose at hour 3 of the OGTT
      were associated with increased risk of gestational hypertension. Maternal
      pregravid BMI also was associated positively with large-for-gestational-age
      infants; both maternal BMI and fasting glucose were associated with birthweight z
      score and neonatal fat mass. CONCLUSION: Among women with untreated mild
      gestational glucose intolerance, pregravid BMI is associated with increased
      gestational hypertension, birthweight, and neonatal fat mass, independent of OGTT
      values.

PMID- 22609022
TI  - Sleep in cognitive life-time trajectory.

PMID- 22609021
TI  - The association between sleep problems and perceived health status: a Japanese
      nationwide general population survey.
AB  - OBJECTIVE: Sleep problems in humans have been reported to impact seriously on
      daily function and to have a close association with well-being. To examine the
      effects of individual sleep problems on physical and mental health, we conducted
      a nationwide epidemiological survey and examined the associations between sleep
      problems and perceived health status. METHODS: Cross-sectional surveys with a
      face-to-face interview were conducted in August and September, 2009, as part of
      the Nihon University Sleep and Mental Health Epidemiology Project (NUSMEP). Data
      from 2559 people aged 20 years or older were analyzed (response rate 54.0%).
      Participants completed a questionnaire on perceived physical and mental health
      statuses, and sleep problems including the presence or absence of insomnia
      symptoms (i.e., difficulty initiating sleep [DIS], difficulty maintaining sleep
      [DMS], and early morning awakening [EMA]), excessive daytime sleepiness (EDS),
      poor sleep quality (PSQ), short sleep duration (SSD), and long sleep duration
      (LSD). RESULTS: The prevalence of DIS, DMS, and EMA was 14.9%, 26.6%, and 11.7%,
      respectively, and 32.7% of the sample reported at least one of them. At the
      complaint level, the prevalence of EDS, PSQ, SSD, and LSD was 1.4%, 21.7%, 4.0%,
      and 3.2%, respectively. Multiple logistic regression analyses revealed that DMS,
      PSQ, SSD, and LSD were independently associated with poor perceived physical
      health status; DIS, EDS, and PSQ were independently associated with poor
      perceived mental health status. CONCLUSIONS: This study has demonstrated that
      sleep problems have individual significance with regard to perceived physical or
      mental health status.

PMID- 22609023
TI  - Thalamic contribution to Sleep Slow Oscillation features in humans: a single case
      cross sectional EEG study in Fatal Familial Insomnia.
AB  - OBJECTIVE: Studying the thalamic role in the cortical expression of the Sleep
      Slow Oscillation (SSO) in humans by comparing SSO features in a case of Fatal
      Familial Insomnia (FFI) and a group of controls. METHODS: We characterize SSOs in
      a 51-year-old male with FFI carrying the D178N mutation and the
      methionine/methionine homozygosity at the polymorphic 129 codon of the PRNP gene
      and in eight gender and age-matched healthy controls. Polysomnographic (21 EEG
      electrodes, two consecutive nights) and volumetric- (Diffusion tensor imaging
      Magnetic Resonance Imaging DTI MRI) evaluations were carried out for the patient
      in the middle course of the disease (five months after the onset of insomnia;
      disease duration: 10 months). We measured a set of features describing each SSO
      event: the wave shape, the event-origin location, the number and the location of
      all waves belonging to the event, and the grouping of spindle activity as a
      function of the SSO phase. RESULTS: We found that the FFI individual showed a
      marked reduction of SSO event rate and wave morphological alterations as well as
      a significant reduction in grouping spindle activity, especially in frontal
      areas. These alterations paralleled DTI changes in the thalamus and the cingulate
      cortex. CONCLUSIONS: This work gives a quantitative picture of spontaneous SSO
      activity during the NREM sleep of a FFI individual. The results suggest that a
      thalamic neurodegeneration specifically alters the cortical expression of the
      SSO. This characterization also provides indications about cortico-thalamic
      interplays in SSO activity in humans.

PMID- 22609024
TI  - Comparison of sleep questionnaires in the assessment of sleep disturbances in
      children with autism spectrum disorders.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to compare two parent
      completed questionnaires, the Modified Simonds & Parraga Sleep Questionnaire
      (MSPSQ) and the Children's Sleep Habits Questionnaire (CSHQ), used to
      characterize sleep disturbances in young children with autism spectrum disorders
      (ASD). Both questionnaires have been used in previous work in the assessment and
      treatment of children with ASD and sleep disturbance. PARTICIPANTS AND METHODS:
      Parents/caregivers of a sample of 124 children diagnosed with ASD with an average
      age of six years completed both sleep questionnaires regarding children's sleep
      behaviors. Internal consistency of the items for both measures was evaluated as
      well as the correlation between the two sleep measures. A Receiver Operating
      Characteristics (ROC) curve analysis was also conducted to examine the predictive
      power of the MSPSQ. RESULTS: More than three quarters of the sample (78%) were
      identified as poor sleepers on the CSHQ. Cronbach's alpha for the items on the
      CSHQ was 0.68 and Cronbach's alpha for items on the MSPSQ was 0.67. The total
      scores for MSPSQ and CSHQ were significantly correlated (r=.70, p<.01). After
      first identifying the poor sleepers based on the CSHQ, an area under the curve
      was 0.89 for the MSPSQ. Using a cut off score of 56 on the MSPSQ, sensitivity was
      .86 and specificity was .70. CONCLUSIONS: In this sample of children with ASD,
      sleep disturbances were common across all cognitive levels. Preliminary findings
      suggest that, similar to the CSHQ, the MSPSQ has adequate internal consistency.
      The two measures were also highly correlated. A preliminary cut off of 56 on the
      MSPSQ offers high sensitivity and specificity commensurate with the widely used
      CSHQ.

PMID- 22609025
TI  - Challenging the sleep homeostat: sleep in depression is not premature aging.
AB  - OBJECTIVES: The close relationship between major depression and sleep
      disturbances led to the hypothesis of a deficiency in homeostatic sleep pressure
      in depression (S-deficiency hypothesis). Many observed changes of sleep
      characteristics in depression are also present in healthy aging, leading to the
      premise that sleep in depression resembles premature aging. In this study, we
      aimed at quantifying the homeostatic sleep-wake regulation in young women with
      major depression and healthy young and older controls under high sleep pressure
      conditions. METHODS: After an 8-h baseline night nine depressed women, eight
      healthy young, and eight healthy older women underwent a 40-h sustained
      wakefulness protocol followed by a recovery night under constant routine
      conditions. Polysomnographic recordings were carried out continuously. Sleep
      parameters as well as the time course of EEG slow-wave activity (SWA) (EEG
      spectra range: 0.75-4.5 Hz), as a marker of homeostatic sleep pressure, were
      analyzed during the recovery night. RESULTS: Young depressed women exhibited
      higher absolute mean SWA levels and a stronger response to sleep deprivation,
      particularly in frontal brain regions. In contrast, healthy older women exhibited
      not only attenuated SWA values compared to the other two groups, but also an
      absence of the frontal SWA predominance. CONCLUSIONS: Homeostatic sleep
      regulation and sleep architecture in young depressed women are not equal to
      premature aging. Moreover, our findings demonstrate that young moderately
      depressed women exhibit no deficiency in the sleep homeostatic process S as
      predicted by the S-deficiency hypothesis, but, rather, live on an elevated level
      of homeostatic sleep pressure.

PMID- 22609026
TI  - Long-term protective effects of hepatitis A vaccines. A systematic review.
AB  - OBJECTIVE: Data on duration and long-term protective effects of hepatitis A
      vaccines (HepA) have not been reviewed using a systematic approach. Our objective
      is to provide a comprehensive review of evidence on the duration of protection
      achieved by HepA, which is needed for revising existing vaccine policies.
      Limitations in data availability and implications for future research in this
      area are discussed. METHODS: A systematic literature review was conducted
      including all studies published between 1997 and 2011 reporting on long-term
      protection of HepA. The outcomes considered were hepatitis A virus (HAV)
      infection and sero-protection measured by anti-HAV antibodies after follow-up
      times of over 5 years post-vaccination. RESULTS: 299 studies were identified from
      MEDLINE and 51 studies from EMBASE. 13 manuscripts met our inclusion criteria.
      The maximum observation times and reported persistence levels of sero-protective
      anti-HAV antibodies was 15 years for live attenuated HepA and 14 years for
      inactivated HepA. All data were from observational studies and showed that higher
      number of doses of live attenuated vaccine led to higher seropositivity and GMT,
      but dosage and schedule did not significantly impact the long-term protection
      following inactivated vaccine. Few comparisons were made between the two vaccine
      types indicating highest levels of antibody titers achieved by multiple doses of
      live attenuated vaccines 7 years post-vaccination. CONCLUSION: Available data
      indicate that both inactivated and live attenuated HepA are capable of providing
      protection up to 15 years as defined by currently accepted, conservative
      correlates of protection. Further investigations are needed to continue to
      monitor the long-term protection afforded by these vaccines. Standardized methods
      are required for vaccine-follow-up studies including assessment of co-variables
      potentially affecting long-term protection.

PMID- 22609027
TI  - Skull vault destruction after rhinocerebral mucormycosis.
AB  - BACKGROUND: Mucormycosis is a relatively rare form of fungal infection that can
      be rapidly progressive. Clinical presentation depends on the anatomic area of
      involvement; however, the commonest form is that of rhinocerebral. CASE
      DESCRIPTION: This is the first case of extensive and progressive destruction of
      the skull vault despite antifungal therapy. The patient required aggressive
      surgical resection to arrest the disease progression and complex reconstruction
      using a custom made titanium cranioplasty. CONCLUSIONS: This report highlights
      the need for early aggressive resection for cases of mucormycosis infection where
      there is bony involvement.

PMID- 22609028
TI  - Synthesis, biodistribution and PET studies in rats of (18)F-Labeled bridgehead
      fluoromethyl analogues of WAY-100635.
AB  - INTRODUCTION: In vitro screening of fluoromethyl bridge-fused ring (BFR)
      analogues of WAY-100635 (5a, 5b and 5c) has shown a high binding affinity and a
      good selectivity for the 5-HT(1A) receptor. As these compounds were designed to
      provide PET ligands with high metabolic stability, they are now radiolabeled with
      fluorine-18 and investigated in vivo. METHODS: BFR precursors were synthesized
      and reacted with fluorine-18 in dry MeCN in the presence of 2,2,2-kryptofix and
      K(2)CO(3). In rats, biodistribution and PET studies were performed using
      [(18)F]5a, [(18)F]5b and [(18)F]5c. The binding specificity was determined by
      administration of non-labeled WAY-100635 prior to the radiolabeled ligands.
      RESULTS: [(18)F]5 ligands were synthesized in overall radiochemical yields of 24%
      45%, respectively with a radiochemical purity of >98%. Relatively good
      hippocampus to cerebellum ratios of 5.55, 4.79 and 5.45, respectively were
      reached at 45 min pi. However, PET studies indicated defluorination of the
      radioligands by showing high accumulation of radioactivity in the bones in the
      order of [(18)F]5a~[(18)F]5b>[(18)F]5c. CONCLUSION: Also in vivo, the
      radioligands bind preferentially to the 5-HT(1A) receptor. Unfortunately, no
      metabolic stability with regard to defluorination was observed in rats.

PMID- 22609029
TI  - [Elevated HDL is the main negative risk factor for coronary artery disease in the
      elderly patient with calcific aortic valve disease].
AB  - In spite of high prevalences of hypertension and hypercholesterolemia, the
      majority of elderly patients admitted for aortic valve surgery due to calcific
      aortic valve disease (CAVD) do not have significant coronary artery disease
      (CAD). OBJECTIVE: To evaluate the lipid profile (LP) of patients undergoing
      surgery for CAVD and to correlate this with coronary angiographic data and prior
      cardiovascular risk factor profile. METHODS: This was a prospective observational
      cohort study of 264 consecutive patients aged >59 years (mean 72), 126 men (48%)
      and 138 women (52%). According to the angiographic presence (irregularities,
      moderate or significant lesions) or absence (normal angiogram) of significant CAD
      respectively, patients were divided into two groups: A (n=127, 48%) and B (n=137,
      52%). A mean of 3.5 classical risk factors were identified in men and 2.6 in
      women. LP (obtained on admission, in the fasting state) included total
      cholesterol (TC), HDL, triglycerides (TG), LDL, and lipoprotein(a). RESULTS: With
      the exception of male gender, diabetes and HDL, the other factors studied -
      smoking, hypertension, TC, TG, LDL (in both statin-treated and non-statin-treated
      patients) and lipoprotein(a) - did not show significant differences between
      groups A and B; LDL was 116 +/- 40mg/dl in group A vs. 123 +/- 38mg/dl in group
      B, in non-statin-treated patients; significant CAD was identified in 64% of men
      vs. 26% of women (p < 0.001); 43% of group A had diabetes vs. 27% of group B
      (p<0.01); HDL was 49 +/- 14mg/dl in group A vs. 59 +/- 16mg/dl in group B (p <
      0.001); HDL in group A was 49 +/- 14 mg/dl in men vs. 49 +/- 13 mg/dl in women
      (NS) and 45 +/- 13 mg/dl in diabetic patients vs. 52 +/- 14 mg/dl in non
      diabetics (p <0.02); HDL in group B diabetic patients was 54 +/- 17 mg/dl in men
      vs. 56 +/- 18 mg/dl in women (NS), and HDL in group B non-diabetic patients was
      55 +/- 13mg/dl in men vs. 63 +/- 17 mg/dl in women (p < 0.02). Multivariate
      analysis showed that only low HDL and diabetes (in women) were independent risk
      factors for significant CAD. The effect of male gender as a risk factor appears
      to be exerted mainly through lower HDL levels. CONCLUSIONS: Elevated HDL is the
      main negative risk factor for significant CAD in elderly high-risk but mildly
      dyslipidemic CAVD patients. HDL does not appear to have any protective effect in
      the pathophysiology of CAVD. In terms of long-term intervention, primary
      prevention of significant CAD should in the future be hybrid, focusing mainly on
      improving HDL function, but also on lowering LDL.

PMID- 22609030
TI  - A prospective treatment protocol for outpatient laparoscopic appendectomy for
      acute appendicitis.
AB  - BACKGROUND: Many laparoscopic procedures are currently performed on an outpatient
      basis. Laparoscopic appendectomy, however, continues to require postoperative
      hospitalization at most institutions. A treatment protocol for outpatient
      laparoscopic appendectomy was developed to determine if this could be
      successfully performed without increasing postoperative complications. We
      hypothesized that adopting an outpatient protocol for laparoscopic appendectomy
      will significantly increase the rate of outpatient management for uncomplicated
      appendicitis, without an increase in morbidity or mortality. STUDY DESIGN: We
      initiated a prospective outpatient protocol for laparoscopic appendectomy in July
      2010 at our institution. All patients having laparoscopic appendectomy from July
      2010 to March 2011 were included as protocol patients and were retrospectively
      reviewed. A separate group of patients having laparoscopic appendectomy from
      January to September 2009 were analyzed as historical controls. These 2 groups
      were compared for demographics, preoperative comorbidities, outpatient
      management, and postoperative morbidity by chi-square analysis, with a 0.95
      confidence level for statistical significance. RESULTS: A total of 116 protocol
      patients were compared with 119 historical control patients. There were no
      significant differences in patient demographics, preoperative comorbidities, and
      pathologic findings between protocol patients and historical controls. Ninety
      nine protocol patients (85.3%) had procedures as outpatients compared with 42
      historical control patients (35.3%; p < 0.05). Postoperative morbidity occurred
      in 6 protocol patients (5.2%) and 10 historical controls (8.4%; p = NS). There
      were no readmissions or mortalities in the protocol group. CONCLUSIONS: An
      outpatient protocol for laparoscopic appendectomy significantly increased the
      rate of outpatient management with no increase in morbidity or mortality. This
      practice has now become standard of care at our institution.

PMID- 22609031
TI  - [Management of pregnancies with a previous cesarean].
AB  - The cesarean rate in France has reached 21% in 2010. With a maintained fertility
      rate, management of a pregnant woman with a previous caesarean scar is becoming a
      daily situation for most obstetrical teams. Considering the small rate of vaginal
      birth after cesarean (VBAC), we will try to establish an up-to-date review of the
      benefits and risks of encouraging trial of VBAC. This information can help
      professionals provide adequate counselling women or couples.

PMID- 22609032
TI  - Threat of the thin-ideal body image and body malleability beliefs: effects on
      body image self-discrepancies and behavioral intentions.
AB  - This study examined the effect of the threat aroused by the perception of thin
      ideal images combined with beliefs about the malleability of the body on
      perceived/objective, ideal/objective and ought/objective body image self
      discrepancies. An experimental computer program enabled women (N=82) to
      artificially increase or decrease the shape of their own body (previously
      photographed) in response to questions about their "actual", "ideal" and "ought"
      body self-perceptions. As predicted, results showed that women had greater body
      self-discrepancies when confronted with threatening thin ideals, regardless of
      their body mass index. The size of this trend depended on the way they were made
      to think of their body (malleable vs. fixed). Findings also suggested a possible
      relationship between body self-representations and eating behaviors or
      intentions. The impact of thin-ideal threats and body malleability beliefs on
      body perception is discussed.

PMID- 22609033
TI  - Considering J.Lo and Ugly Betty: a qualitative examination of risk factors and
      prevention targets for body dissatisfaction, eating disorders, and obesity in
      young Latina women.
AB  - Latina women are vulnerable to poor body image, eating disorders, and obesity,
      particularly during the college years. This study sought to identify common
      cultural antecedents of these concerns in order to inform the development of
      prevention programs for this population. Six groups of university students who
      identified as Latina (N=27) discussed cultural aspects of body image, eating
      disorders, and obesity. Thematic analysis identified four main themes: (a)
      cultural disparities in body-ideal, including the influence of the media and
      acculturation issues; (b) messages about body shape and weight received by
      family, peers, and society; (c) difficulties making healthy eating and physical
      activity choices as a function of college life; and (d) the influence of peers
      and potential male partners on body satisfaction and body-ideals. These results
      have implications for the development of programs targeting body dissatisfaction
      and risk for eating disorders and obesity in Latina college women.

PMID- 22609034
TI  - Anorexia nervosa and the kidney.
AB  - Anorexia nervosa is a common psychiatric disorder that disproportionately affects
      adolescents and young adults and is associated with high rates of morbidity and
      mortality. Anorexia nervosa can affect the kidney in numerous ways, including
      increased rates of acute kidney injury and chronic kidney disease, electrolyte
      abnormalities, and nephrolithiasis. Additionally, the diagnosis and treatment of
      anorexia nervosa-associated kidney diseases are challenging, reflecting
      complications such as refeeding syndrome, as well as the limitations of serum
      creatinine level in this population to estimate kidney function and the
      psychosocial challenges inherent with treating systemic manifestations of
      psychiatric conditions. In this review, we discuss kidney diseases and kidney
      associated conditions that occur in individuals with anorexia nervosa,
      summarizing many of the challenges in treating patients with this disease.

PMID- 22609037
TI  - WITHDRAWN: Trends in vaccination coverage disparities among children, United
      States, 2001-2010.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 22609035
TI  - Antigenic and immunogenic properties of recombinant hemagglutinin proteins from
      H1N1 A/Brisbane/59/07 and B/Florida/04/06 when produced in various protein
      expression systems.
AB  - Antibodies directed against the influenza hemagglutinin (HA) protein largely
      mediate virus neutralization and confer protection against infection.
      Consequently, many studies and assays of influenza vaccines are focused on HA
      specific immune responses. Recombinant HA (rHA) proteins can be produced in a
      number of protein expression and cell culture systems. These range from
      baculovirus infection of insect cell cultures, to transient transfection of
      plants, to stably transfected human cell lines. Furthermore, the rHA proteins may
      contain genetic modifications, such as histidine tags or trimerization domains,
      intended to ease purification or enhance protein stability. However, no
      systematic study of these different forms of the HA protein have been conducted.
      It is not clear which, if any, of these different protein expression systems or
      structural modifications improve or diminish the biological behavior of the
      proteins as immunogens or antigens in immune assays. Therefore we set out to
      perform systematic evaluation of rHA produced in different proteins expression
      systems and with varied modifications. Five rHA proteins based on recent strains
      of seasonal influenza A and five based on influenza B HA were kindly provided by
      the Biodefense and Emerging Infections Reagent Repository (BEIR). These proteins
      were evaluated in a combination of biochemical and structural assays, in vitro
      humoral and cellular immune assays, and in an animal vaccination model. Marked
      differences in the behavior of the individual proteins was evident suggesting
      that they are not equal when being used to detect an immune response. They were,
      nevertheless, similar at eliciting neutralizing antibody responses.

PMID- 22609036
TI  - Use of human MonoMac6 cells for development of in vitro assay predictive of
      adjuvant safety in vivo.
AB  - Subunit vaccines composed of recombinant or purified antigens have a good safety
      record but are poorly immunogenic and require adjuvants to activate innate
      immunity and facilitate antigen specific immune response. Of the many adjuvant
      formulations that are under development, very few are licensed mainly due to
      concerns about adverse side effects. The goal of our study was to develop in
      vitro assays that could predict toxicity of adjuvants in vivo. Pro-inflammatory
      cytokines IL-beta, IL-6, TNF-alpha, and IL-8 were measured in human primary
      monocytes and the monocytoid cell line, MonoMac 6 (MM6), activated with a panel
      of TLR agonists or with adjuvants. A 0.5 EU/ml dose of Standard for endotoxin
      (previously shown to provide a margin between pyrogenic and non-pyrogenic
      substances in rabbits) was used as a comparator to establish a "safety
      threshold". FSL-1, Pam3CSK4, flagellin, and R848 TLR agonists but not Alum, MF59,
      Poly I:C, or MPL adjuvants induced cytokines in MM6 cells above the safety
      threshold. To confirm the predictive value of the in vitro assays, FSL-1 and
      flagellin were injected intramuscularly into New Zealand White (NZW) rabbits.
      Both TLR agonists induced fever within 6-8h post-injection followed 24-48 h later
      by increased C reactive protein (CRP). Importantly, an early peak in plasma
      prostaglandin E2 (PGE(2)) levels preceded rise in body temperature. In vitro
      production of PGE(2) in monocytes and MM6 cells was found following treatments
      with various TLR agonists but not with alum, MF59, MPL, or Poly I:C adjuvants.
      Together, our studies demonstrated a strong correlation between production of pro
      inflammatory cytokines above a "safety threshold" and production of PGE(2)in
      vitro and an increase in body temperature in rabbits. The developed human cell
      based assays could provide an important tool for early screening of new molecular
      moieties and adjuvant formulations and may assist in selection of safer products.

PMID- 22609038
TI  - An international opinion research survey of the etiology, diagnosis, therapy and
      outcome of Kienbock's disease (KD).
AB  - OBJECTIVES: Every fourth publication on Kienbock's disease (KD) is based for the
      most part on rather divergent expert opinion. We therefore surveyed expert
      opinion on KD in three European countries: (1) for the suspected aetiologies; (2)
      routinely used diagnostic tools; (3) recommended treatment and (4) expected
      outcome. METHODS: A questionnaire consisting of 16 questions was handed out at
      the national meetings for surgery of the hand in Germany (DE), France (FR) in
      2009 and in the United Kingdom (UK) in 2010. RESULTS: Among the 126 surgeons who
      participated in the survey, 82 had a national diploma for surgery of the hand.
      None of the most commonly discussed etiopathological hypotheses were estimated as
      being very likely. Hand/arm vibration exposure was considered less likely among
      respondents in France and the UK than among respondents in Germany. Treatment
      recommendations are very heterogeneous for stage IIIB according to Lichtman.
      CONCLUSIONS: Expert opinions on diagnostic criteria, the pathogenesis and the
      choice of treatment are not consistent and may vary from one country to another.

PMID- 22609039
TI  - Tuning the rigging before sailing off into the stormy sea of stem cell
      transplants for patients with myelodysplastic syndromes.

PMID- 22609040
TI  - Busulfan, fludarabine, and alemtuzumab as a reduced toxicity regimen for children
      with malignant and nonmalignant diseases improves engraftment and graft-versus
      host disease without delaying immune reconstitution.
AB  - For children receiving allogeneic hematopoietic stem cell transplants (HSCTs),
      the toxicity of the conditioning regimen and graft failure remain challenges. We
      previously reported that targeted i.v. busulfan, fludarabine, and rabbit anti
      thymocyte globulin (rATG) decreased toxicity but had a graft failure rate of 21%.
      To improve the engraftment rate, we replaced ATG with alemtuzumab, a monoclonal
      Ab targeting CD52. Thirty-five children with malignant and nonmalignant diseases
      were enrolled in this phase II prospective study. Twelve children had HLA-matched
      related donors (MRDs), 16 had 10 of 10, and 7 had 9 of 10 HLA allele-matched
      unrelated donors (MUDs). Thirty-one of 34 evaluable patients (91%) achieved a
      durable engraftment. All 3 patients who rejected had a nonmalignant disease and
      received a MUD transplantation (2 mismatched at 1 antigen). Three patients died
      of a transplantation-related complication (9% +/- 5.2%). Seven patients had
      disease relapse or progression, 2 of whom died. At a median follow-up of 35
      months (range, 15-85 months), the event-free survival (EFS) was 61% +/- 9.0% and
      the overall survival (OS) was 78% +/- 7.5%. The median time to neutrophil
      recovery, B cell, and T cell reconstitution were 16 days, 3 months, and 6 months,
      respectively. At 1 year, the median donor chimerism in whole blood, CD3, CD14/15,
      and CD19 subsets were 97%, 87%, 100%, and 99%, respectively. Six patients (17% +/
      6.6%) developed acute graft-versus-host disease (aGVHD), only 2 of which were
      >grade II. Two patients (8% +/- 5.4%) progressed to chronic GVHD (cGVHD). These
      results suggest that replacement of rATG with alemtuzumab may improve engraftment
      as well as decrease cGVHD rates without resulting in delays in immune
      reconstitution.

PMID- 22609041
TI  - Age-related neuromuscular adaptation does not affect the mechanical efficiency of
      lower limbs during walking.
AB  - Ageing involves modifications of the locomotor system which is believed to
      increase energy consumption. This study aimed at verifying whether neuromuscular
      adaptation due to ageing, in conjunction with age-related modifications of the
      muscle-tendon actuators, involves greater muscle-tendon workload. Ten young and 7
      elderly healthy subjects were assessed using gait analysis while walking at
      comparable speed. Planar models of muscle-driven locomotion, accounting for 14
      muscles grouped into 9 equivalent actuators, were developed. Muscle-tendon forces
      were estimated by using the inverse-dynamic based static optimization where cost
      functions were tuned to capture the different muscle co-activation between
      groups. Following this, tendon and muscle shortening/lengthening was computed,
      and muscle-tendon work was estimated and compared between groups. Results showed
      that both groups produced comparable muscle mechanical work, though shared
      differently among muscles. In particular, young subjects showed a greater
      workload of ankle plantaflexor muscles and older subjects used greater eccentric
      energy at the knee extensors during stance phase. Moreover, young people used
      more elastic energy than older people. These findings suggest that the
      combination adaptation due to ageing, in conjunction with age-related
      modifications of the muscle-tendon actuators, do not significantly increase the
      overall energetic output of locomotion. Moreover, the motor control system
      appears to be characterised by a degree of adaptation which allows older
      individuals to achieve biomechanical efficiency comparable to younger subjects.

PMID- 22609042
TI  - Assessment of the postural control strategies used to play two Wii FitTM
      videogames.
AB  - The Nintendo Wii FitTM may provide an affordable alternative to traditional
      biofeedback or virtual reality systems for retraining or improving motor function
      in populations with impaired balance. The purpose of this study was to evaluate
      postural control strategies healthy individuals use to play Wii FitTM videogames.
      Sixteen young adults played 10 trials of Ski Slalom and Soccer Heading
      respectively. Centre of pressure (COP) excursion and three-dimensional movement
      data were acquired to determine variability in medial-lateral COP sway and
      shoulder-pelvic movement. While there was no difference in medial-lateral COP
      variability between games during trial 1, there was a significant difference
      after 10 trials. COP sway increased (59-75 mm) for Soccer Heading while it
      decreased (67-33 mm) for Ski Slalom from trial 1 to trial 10. During Ski Slalom
      participants demonstrated decreased shoulder and pelvic movement combined with
      increased pelvic-shoulder coupling. Conversely, participants demonstrated greater
      initial shoulder tilt when playing Soccer Heading, with no reduction in pelvic
      rotation and tilt. Participants decreased pelvic and trunk movements when skiing,
      suggesting a greater contribution of lower extremity control while they primarily
      used a trunk strategy to play Soccer Heading.

PMID- 22609043
TI  - Evidence for age-related decline in visuomotor function and reactive stepping
      adjustments.
AB  - This study investigated age-related and fall-risk-related differences in the
      ability to make visually guided reactive stepping adjustments during locomotion.
      Participants were asked to walk towards and step accurately onto a visual target
      which, during the step towards it, moved to an unpredictable location at an
      unpredictable time. We measured lower limb kinematics and eye movement
      characteristics of young adults and two groups of older adults deemed to be
      either at a low- or high-risk of falling. High-risk older adults produced
      significant deviations in foot trajectory with latencies of ~300 ms, compared to
      280 ms in low-risk older adults and ~200 ms in young adults. Furthermore, high
      risk older adults were unable to generate adjustments with the same magnitude and
      consistency as low-risk older adults and young adults. Saccadic reaction
      latencies also were doubled in high-risk older adults compared to young. Analysis
      of covariance showed that the significant between group differences in final foot
      placement error could be accounted for by differences in saccadic response times.
      We propose that age-related delays in visuomotor processing times may disrupt the
      timing and magnitude of stepping adjustments, possibly contributing to an
      increased likelihood of falls.

PMID- 22609044
TI  - Waking and dreaming consciousness: neurobiological and functional considerations.
AB  - This paper presents a theoretical review of rapid eye movement sleep with a
      special focus on pontine-geniculate-occipital waves and what they might tell us
      about the functional anatomy of sleep and consciousness. In particular, we review
      established ideas about the nature and purpose of sleep in terms of
      protoconsciousness and free energy minimization. By combining these theoretical
      perspectives, we discover answers to some fundamental questions about sleep: for
      example, why is homeothermy suspended during sleep? Why is sleep necessary? Why
      are we not surprised by our dreams? What is the role of synaptic regression in
      sleep? The imperatives for sleep that emerge also allow us to speculate about the
      functional role of PGO waves and make some empirical predictions that can, in
      principle, be tested using recent advances in the modeling of
      electrophysiological data.

PMID- 22609045
TI  - Pathogenesis and therapy of spinal and bulbar muscular atrophy (SBMA).
AB  - Spinal and bulbar muscular atrophy (SBMA) is a late-onset motor neuron disease
      characterized by slowly progressive muscle weakness and atrophy. During the last
      two decades, basic and clinical research has provided important insights into the
      disease phenotype and pathophysiology. The cause of SBMA is the expansion of a
      trinucleotide CAG repeat encoding a polyglutamine tract within the first exon of
      the androgen receptor (AR) gene. SBMA exclusively affects adult males, whereas
      females homozygous for the AR mutation do not manifest neurological symptoms. The
      ligand-dependent nuclear accumulation of the polyglutamine-expanded AR protein is
      central to the gender-specific pathogenesis of SBMA, although additional steps,
      e.g., DNA binding, inter-domain interactions, and post-translational modification
      of AR, modify toxicity. The interactions with co-regulators are another requisite
      for the toxic properties of the polyglutamine-expanded AR. It is also shown that
      the polyglutamine-expanded AR induces diverse molecular events, such as
      transcriptional dysregulation, axonal transport disruption, and mitochondrial
      dysfunction, which play causative roles in the neurodegeneration in SBMA. The
      pathogenic AR-induced myopathy also contributes to the non-cell autonomous
      degeneration of motor neurons. Pre-clinical studies using animal models show that
      the pathogenic AR-mediated neurodegeneration is suppressed by androgen
      inactivation, the efficacy of which has been tested in clinical trials.
      Pharmacological activation of cellular defense machineries, such as molecular
      chaperones, ubiquitin-proteasome system, and autophagy, also exerts
      neuroprotective effects in experimental models of SBMA.

PMID- 22609046
TI  - Specificity of peripheral nerve regeneration: interactions at the axon level.
AB  - Peripheral nerves injuries result in paralysis, anesthesia and lack of autonomic
      control of the affected body areas. After injury, axons distal to the lesion are
      disconnected from the neuronal body and degenerate, leading to denervation of the
      peripheral organs. Wallerian degeneration creates a microenvironment distal to
      the injury site that supports axonal regrowth, while the neuron body changes in
      phenotype to promote axonal regeneration. The significance of axonal regeneration
      is to replace the degenerated distal nerve segment, and achieve reinnervation of
      target organs and restitution of their functions. However, axonal regeneration
      does not always allows for adequate functional recovery, so that after a
      peripheral nerve injury, patients do not recover normal motor control and fine
      sensibility. The lack of specificity of nerve regeneration, in terms of motor and
      sensory axons regrowth, pathfinding and target reinnervation, is one the main
      shortcomings for recovery. Key factors for successful axonal regeneration include
      the intrinsic changes that neurons suffer to switch their transmitter state to a
      pro-regenerative state and the environment that the axons find distal to the
      lesion site. The molecular mechanisms implicated in axonal regeneration and
      pathfinding after injury are complex, and take into account the cross-talk
      between axons and glial cells, neurotrophic factors, extracellular matrix
      molecules and their receptors. The aim of this review is to look at those
      interactions, trying to understand if some of these molecular factors are
      specific for motor and sensory neuron growth, and provide the basic knowledge for
      potential strategies to enhance and guide axonal regeneration and reinnervation
      of adequate target organs.

PMID- 22609047
TI  - The human sexual response cycle: brain imaging evidence linking sex to other
      pleasures.
AB  - Sexual behavior is critical to species survival, yet comparatively little is
      known about the neural mechanisms in the human brain. Here we systematically
      review the existing human brain imaging literature on sexual behavior and show
      that the functional neuroanatomy of sexual behavior is comparable to that
      involved in processing other rewarding stimuli. Sexual behavior clearly follows
      the established principles and phases for wanting, liking and satiety involved in
      the pleasure cycle of other rewards. The studies have uncovered the brain
      networks involved in sexual wanting or motivation/anticipation, as well as sexual
      liking or arousal/consummation, while there is very little data on sexual satiety
      or post-orgasmic refractory period. Human sexual behavior also interacts with
      other pleasures, most notably social interaction and high arousal states. We
      discuss the changes in the underlying brain networks supporting sexual behavior
      in the context of the pleasure cycle, the changes to this cycle over the
      individual's life-time and the interactions between them. Overall, it is clear
      from the data that the functional neuroanatomy of sex is very similar to that of
      other pleasures and that it is unlikely that there is anything special about the
      brain mechanisms and networks underlying sex.

PMID- 22609049
TI  - Tarsoconjunctival crypts: unrecognized cause of chronic mucopurulent
      conjunctivitis.
AB  - PURPOSE: To describe 3 patients with chronic mucopurulent conjunctivitis found to
      have an unrecognized sequestration of bacteria within tarsoconjunctival crypts of
      the upper eyelid. DESIGN: Review of 3 noncomparative cases. METHODS: settings:
      Institutional. study population: Three consecutive patients with
      tarsoconjunctival crypts. intervention procedure: Marsupialization of the
      individual crypts. main outcome measures: Resolution of chronic discharge and
      resolution of signs and symptoms. RESULTS: One patient with Stevens-Johnson
      syndrome and 2 patients with floppy eyelids had chronic mucopurulent
      conjunctivitis that was refractory to multiple medical and surgical
      interventions. Retention of a yellowish coagulum within the fistulous tracts of
      the tarsal conjunctiva was the site of pathologic features in all patients. The
      diagnosis was confirmed by squeezing out of the coagulum from the fistulous
      tracts by pinching the eyelid horizontally. Pseudomonas aeruginosa was isolated
      in 1 patient and Staphylococcus aureus was isolated in the other 2 patients. A
      Bowman probe could be passed through the fistulous opening to unveil the full
      extent of the conjunctival tunnels on the epitarsal surface. Each tract was
      marsupialized, and no relapse was found during a follow-up period of 12 to 96
      months. CONCLUSIONS: Patients with chronic, relapsing, purulent conjunctivitis
      should have their upper eyelid everted to search for tarsoconjunctival crypts as
      the source of bacteria-laden coagulum. The formation of the crypts is likely the
      result of tarsal conjunctiva trauma with lamellar de-epithelialization, followed
      by re-epithelialization to form an epithelialized tunnel as a potential space for
      harboring bacteria. Marsupialization of the crypts obliterates the potential
      space and is curative.

PMID- 22609048
TI  - Cannabinoid receptors mediate methamphetamine induction of high frequency gamma
      oscillations in the nucleus accumbens.
AB  - Patients suffering from amphetamine-induced psychosis display repetitive
      behaviors, partially alleviated by antipsychotics, which are reminiscent of
      rodent stereotypies. Due to recent evidence implicating endocannabinoid
      involvement in brain disorders, including psychosis, we studied the effects of
      endocannabinoid signaling on neuronal oscillations of rats exhibiting
      methamphetamine stereotypy. Neuronal network oscillations were recorded with
      multiple single electrode arrays aimed at the nucleus accumbens of freely-moving
      rats. During the experiments, animals were dosed intravenously with the CB1
      receptor antagonist rimonabant (0.3 mg/kg) or vehicle followed by an ascending
      dose regimen of methamphetamine (0.01, 0.1, 1, and 3 mg/kg; cumulative dosing).
      The effects of drug administration on stereotypy and local gamma oscillations
      were evaluated. Methamphetamine treatment significantly increased high frequency
      gamma oscillations (~80 Hz). Entrainment of a subpopulation of nucleus accumbens
      neurons to high frequency gamma was associated with stereotypy encoding in
      putative fast-spiking interneurons, but not in putative medium spiny neurons. The
      observed ability of methamphetamine to induce both stereotypy and high frequency
      gamma power was potently disrupted following CB1 receptor blockade. The present
      data suggest that CB1 receptor-dependent mechanisms are recruited by
      methamphetamine to modify striatal interneuron oscillations that accompany
      changes in psychomotor state, further supporting the link between
      endocannabinoids and schizophrenia spectrum disorders.

PMID- 22609050
TI  - Clinical significance of the serum crosslinked N-telopeptide of type I collagen
      as a prognostic marker for non-small-cell lung cancer.
AB  - INTRODUCTION: Lung cancer is the leading cause of cancer-related death. Many
      patients with lung cancer are in its advanced stages at the time of diagnosis.
      The 5-year survival rate for lung cancer is 10% to 20%, and the prognosis for
      patients with lung cancer is still poor. The crosslinked N-terminal telopeptide
      of type I collagen (NTx) is a metabolite of type I collagen, the main constituent
      of bone matrix. PATIENTS AND METHODS: We measured serum NTx levels in patients
      who underwent staging during hospitalization for the initial treatment of lung
      cancer in our department. We examined whether serum NTx levels would be relevant
      to the prognosis of non-small-cell lung cancer (NSCLC). RESULTS: This study
      included 176 patients with lung cancer (125 men and 51 women), including 109 with
      adenocarcinoma, 53 with squamous cell carcinoma, 6 with large-cell carcinoma, and
      8 with other cancer types. Univariate and multivariate analysis using the Cox
      proportional hazards model revealed a particularly close association between sex,
      performance status, disease stage, and serum NTx levels and overall survival
      (OS). A median OS of 368 days was observed for patients with a serum NTx level <
      22 nmol BCE/L, which was significantly longer than the 197 days for patients with
      a serum NTx level >= 22 nmol BCE/L (hazard ratio [HR], 2.02; 95% confidence
      interval [CI], 1.36-2.99; log-rank P = .00037). CONCLUSIONS: We have revealed
      that a high serum NTx level (> 22 nmol BCE/L) appears to be a risk factor for a
      reduction in OS in patients with NSCLC.

PMID- 22609051
TI  - Chemotherapy is beneficial for elderly patients with advanced non-small-cell lung
      cancer: analysis of patients aged 70-74, 75-79, and 80 or older in Japan.
AB  - BACKGROUND: It remains to be determined in elderly patients with advanced non
      small-cell lung cancers (NSCLCs) if there is a benefit of chemotherapy in
      patients aged 80 or older. METHODS: Using a database from the Japan National
      Hospital Organization Study Group for Lung Cancer from 1990 to 2005, 3 cohorts
      based on the age of diagnosis were examined in patients with stage IIIB and IV
      NSCLC. Cohort 1 was for 70- to 74-year-old patients, cohort 2 for 75- to 79-year
      old, and cohort 3 for 80 years and older (80+). Multivariate analysis of survival
      for each cohort was performed using the Cox regression method using the following
      covariates: age, PS, histology, stage, smoking status, and chemotherapy. RESULTS:
      There were 1617 patients in cohort 1, 1349 in cohort 2, and 1010 in cohort 3. The
      number of patients treated with chemotherapy were 991 (61%) in cohort 1, 648
      (48%) in cohort 2, and 286 (28%) in cohort 3. Multivariate analysis for overall
      survival (OS) showed that chemotherapy was a significant prognostic factor among
      cohort 1 (hazard ratio [HR], 0.540; 95% confidence interval [CI], 0.481-0.607; P
      < .0001) and cohort 2 (HR, 0.715; 95% CI, 0.632-0.810; P < .0001) and showed a
      benefit trend among cohort 3 (HR, 0.869; 95% CI, 0.742-1.018; P = .0940).
      CONCLUSIONS: After adjustment for PS, a trend of survival benefit of chemotherapy
      remained in patients aged 80 or older.

PMID- 22609052
TI  - The use of the dual-task paradigm in detecting gait performance deficits
      following a sports-related concussion: a systematic review and meta-analysis.
AB  - OBJECTIVES: The purpose of this systematic review was to determine the viability
      of the dual-task paradigm in the evaluation of a sports-related concussion.
      DESIGN: Systematic review and meta-analysis. METHODS: Eight electronic databases
      were searched from their inception until the 11(th) of April 2011. Studies were
      grouped according to their reported gait performance variables and their time(s)
      of assessment(s). Raw mean differences (MD) and 95% confidence intervals (CI)
      were calculated based on raw means and standard deviations for gait performance
      measures in both single- and dual-task conditions. Dual-task deficits were pooled
      using a random effects model and heterogeneity (I(2)) between studies was
      assessed. RESULTS: Ten studies representing a total sample of 168 concussed and
      167 matched (age and gender) non-concussed participants met the inclusion
      criteria. Meta-analysis demonstrated that dual-task performance deficits were
      detected (p<0.05) in the concussed group for gait velocity (GV) (MD=-0.133; 95%
      CI -0.197, -0.069) and range of motion of the centre of mass in the coronal plane
      (ML-ROM) (MD=0.007; 95% CI 0.002, 0.011), but not in the non-concussed group; GV
      (MD=-0.048; 95% CI -0.101, 0.006), ML-ROM (MD=0.002; 95% CI -0.001, 0.005).
      CONCLUSIONS: The results of this study indicate that GV and ML-ROM are sensitive
      measures of dual-task related changes in concussed patients and should be
      considered as part of a comprehensive assessment for a sports-related concussion.

PMID- 22609054
TI  - Severe insulin allergy successfully treated with continuous subcutaneous insulin
      infusion.
AB  - Insulin allergy is a rare complication of insulin therapy. Proper management,
      though difficult, is critical. Here, we report the case of a patient with type 2
      diabetes and insulin allergy, successfully treated with continuous subcutaneous
      insulin infusion (CSII).

PMID- 22609053
TI  - Role of ceramides in nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a chronic disease with a histological
      spectrum ranging from steatosis alone, to nonalcoholic steatohepatitis (NASH).
      The latter is associated with an increased risk for progression to cirrhosis.
      Ceramides are a lipid species that exert biological effects through cellular
      proliferation, differentiation, and cell death, and interact with several
      pathways involved in insulin resistance, oxidative stress, inflammation, and
      apoptosis, all of which are linked to NAFLD. We propose a mechanism through which
      ceramides contribute to the development of NAFLD and progression to NASH, due in
      part to second messenger effects via tumor necrosis factor (TNF)-alpha. A better
      understanding of the role of ceramides in steatohepatitis has both diagnostic and
      therapeutic implications for the treatment of fatty liver disease.

PMID- 22609055
TI  - Deterioration of cardiac autonomic function over a period of one year in relation
      to cardiovascular and somatic neuropathy complications in type 2 diabetes
      mellitus.
AB  - AIMS: Progression of cardiac autonomic dysfunction (CADF) in relation to severity
      of diabetic autonomic neuropathy is well documented. But its progression while
      coexisting with somatic neuropathy (PNP) and cardiovascular disease (CVD) is less
      described. We monitored CADF over a period of one year in relation to PNP and CVD
      in patients with type 2 diabetes mellitus. METHODS: Cardiac autonomic function
      was assessed in 104 type 2 diabetics. Based on complications study subjects were
      divided into four subgroups: Group A (No complications); Group B (with CVD);
      Group C (with PNP); Group D (with CVD and PNP). The parameters measured were:
      Expiratory:Inspiratory ratio (E:I ratio) and standard deviation of all the N-N
      intervals (SDNN). These parameters were measured at the baseline and at follow
      up. Data analysis was done by employing suitable statistical tests. RESULTS: In
      Group B: SDNN declined (p<0.001); E:I ratio did not change. In Group C: E:I ratio
      declined (p<0.01); SDNN did not change. In Group D: SDNN and E:I ratio declined
      significantly (p<0.001). CONCLUSION: CADF coexisting with PNP and CVD
      deteriorates with time. E:I ratio and SDNN are suitable markers in monitoring
      CADF coexisting with PNP and CVD respectively in type 2 diabetes mellitus.

PMID- 22609056
TI  - Long-term changes of the prevalence and control rate of hypertension among Korean
      adults with diagnosed diabetes: 1998-2008 Korean National Health and Nutrition
      Examination Survey.
AB  - AIMS: We investigated the long-term changes in the prevalence and the control
      rate of hypertension among Korean adults diagnosed with diabetes. METHODS: Using
      data from the Korean National Health and Nutrition Examination Survey (1998
      2008), including 1384 adults diagnosed with diabetes, we analyzed changes in the
      prevalence of hypertension (mean SBP >= 140 mmHg, DBP >= 90 mmHg, or use of
      antihypertensive medication) and the control rate of hypertension (BP < 130/80
      mmHg). RESULTS: The prevalence of hypertension in diabetic adults was 50.9% in
      1998 and 51.7% in 2008 (P = 0.563). The mean blood pressure decreased from 138.1
      +/- 1.1/80.0 +/- 0.6 mmHg to 124.7 +/- 0.8/76.0 +/- 0.5 mmHg (P < 0.001);
      awareness (37.4 to 85.2%, P < 0.001), treatment (37.4 to 81.8%, P < 0.001), and
      the control rate (20.1 to 34.7%, P = 0.001) steadily increased. The prevalence of
      hypertension increased significantly more in the obese group compared with the
      non-obese group (53.3% vs. 49.0% in 1998, P = 0.784; 64.3% vs. 42.0% in 2008, P <
      0.0001, respectively, P for trend = 0.0001). CONCLUSIONS: Although the rates of
      hypertension treatment have significantly improved, the control rate remains
      inadequate, and intensive intervention is urgently needed.

PMID- 22609057
TI  - Impact of diabetes on the presenting features of tuberculosis in hospitalized
      patients.
AB  - INTRODUCTION: Diabetes mellitus (DM) is a risk factor for tuberculosis (TB) and
      may modify its presenting features. The aim of this study was to find out the
      influence of DM on clinical, radiological and treatment features of TB in
      hospitalized patients. MATERIAL AND METHODS: In a retrospective study we reviewed
      the records of 123 patients with TB and DM admitted from 2000 to 2008 and
      compared this group with another one of 123 patients with TB without DM. RESULTS:
      Although in both groups multilobar lung lesions predominated, there were more
      cases of isolated lower lung field (LLF) involvement in diabetics than in
      nondiabetics (10.6% vs 3.3% p=0.03). Cavitary lesions were less frequent (63.4%
      vs 82.1% p=0.01) and extra-pulmonary TB manifestations were more frequent (28.5%
      vs 16.3% p=0.02) in diabetics than in nondiabetics. There were no significant
      differences between groups regarding multidrug resistant - TB (MDR-TB) and
      adverse effects of anti-tuberculosis drugs. The in-hospital mortality was higher
      in diabetics (8.1% vs 0.8% p=0.01), but using a binary logistic regression there
      was significant difference in mortality only in respect to the variable MDR-TB.
      CONCLUSIONS: This study showed that DM affected some clinical and radiological
      presenting features in hospitalized TB patients. LLF involvement and extra
      pulmonary TB manifestations were more frequent in diabetic patients than in
      nondiabetic ones.

PMID- 22609058
TI  - DNMT1: an emerging target in the treatment of invasive urinary bladder cancer.
AB  - OBJECTIVES: More than 14,000 people die from invasive urothelial carcinoma (iUC)
      of the urinary bladder each year in the USA, and more effective therapies are
      needed. Naturally occurring canine iUC very closely resembles the disease in
      humans and serves as a highly relevant translational model for novel therapy of
      human iUC. Work was undertaken to identify new targets for anticancer therapy in
      dogs with the goal of translating successful therapeutic strategies into humans
      with iUC. MATERIALS AND METHODS: Microarray expression analyses were conducted on
      mRNA extracted from canine normal bladder (n = 4) and iUC tissues (n = 4) using
      Genome Array 1.0 and analyzed by GeneSpring GX 11, with the stringency of P <
      0.02 and a >= 2-fold change. The genes thus identified were further analyzed for
      functional and pathway analysis using Protein ANalysis THrough Evolutionary
      Relationships (PANTHER) Classification System. In selecting genes for further
      study, consideration was given for evidence of a role of the gene in human iUC.
      From these analyses, DNA methyltransferase 1 (DNMT1) was selected for further
      study. Immunohistochemistry (IHC) of canine normal bladder and iUC tissues was
      performed to confirm the microarray expression analyses. The effects of targeting
      DNMT1 in vitro was assessed through MTT assay and Western blot of canine iUC
      cells treated with 5-azacitidine (5-azaC) and trichostatin A (TSA). RESULTS:
      DNMT1 was expressed in 0 of 6 normal canine bladder samples and in 10 of 22 (45%)
      canine iUC samples. The proliferation of canine iUC cells was inhibited by 5-azaC
      (at concentrations >= 5 MUm) and by TSA (at concentrations >= 0.1 MUm). Western
      blot results were supportive of DNMT1-related effects having a role in the
      antiproliferative activity. CONCLUSIONS: Microarray expression analyses on canine
      tissues identified DNMT1 as a potentially "targetable" gene. Expression of DNMT1
      in canine iUC was confirmed by IHC, and in vitro studies confirmed that drugs
      that inhibit DNMT1 have antiproliferative effects. These findings are similar to
      those recently reported in human iUC and are also in line with results of a
      preclinical (prehuman) trial of 5-azaC in dogs with naturally occurring iUC.
      DNMT1 has excellent potential as a target for iUC therapy in humans.

PMID- 22609059
TI  - Plasma thymosin-alpha1 level as a potential biomarker in urothelial and renal
      cell carcinoma.
AB  - OBJECTIVES: To determine the plasma levels of thymosin-alpha1 (TA1) and
      prothymosin-alpha (PTMA) proteins in renal cell carcinoma (RCC) or urothelial
      carcinoma (UC) patients, and explore the potential of these 2 molecules as
      biomarkers. MATERIALS AND METHODS: Blood samples were taken from 50 consecutive
      patients with RCC, 97 with UC, and 55 with benign urologic diseases before
      surgery. Their clinical characteristics were obtained from medical record review.
      Plasma TA1 and PTMA levels were measured using enzyme-linked immunosorbent assay
      and their correlation with tumor grade, pathologic stage, and survival were
      explored. RESULTS: Plasma TA1 levels were significantly lower in RCC patients
      than in UC or benign patients, particularly in UC of the renal pelvis patients (P
      < 0.0001). Plasma PTMA levels were also significantly lower in UC patients
      compared with RCC patients and benign patients (P < 0.05). Plasma TA1 levels
      inversely correlated with pathologic stage both in bladder cancer and RCC
      patients (P = 0.03 and 0.02, respectively). Both plasma TA1 and PTMA did not
      correlate with tumor grade. Plasma TA1 was a prognostic indicator for progression
      free and disease-specific overall survival in bladder cancer patients (P = 0.008
      and 0.04, respectively). CONCLUSIONS: Plasma TA1 level may be a biomarker for
      differentiating between UC and RCC. It may also be a prognostic factor for
      disease progression and disease-specific survival in bladder cancer patients.
      These findings warrant more studies for validation.

PMID- 22609060
TI  - Peer substance use as a mediator between early pubertal timing and adolescent
      substance use: longitudinal associations and moderating effect of maltreatment.
AB  - BACKGROUND: Early pubertal timing has received considerable empirical support as
      a risk for adolescent substance use. However, few studies have examined the
      mediators linking these variables. Therefore, the aims of this study were (1) to
      examine peer substance use as a mediator between pubertal timing and adolescent
      substance use longitudinally and (2) to test gender and maltreatment experience
      as moderators of the mediational model. METHODS: Data were obtained from time 1,
      2, and 3 of a longitudinal study of maltreatment and development. At time 1 the
      sample was comprised of 303 maltreated and 151 comparison children aged 9-13
      years (213 females and 241 males). Longitudinal mediation was tested using
      structural equation modeling and moderating effects were tested using multiple
      group analysis. RESULTS: Peer substance use mediated the relationship between
      early pubertal timing and later adolescent substance use for the total sample.
      Moderation analyses indicated this significant indirect effect did not differ for
      males and females. However, it did differ for maltreated versus comparison
      adolescents with the mediational effect only remaining significant for the
      comparison group. CONCLUSIONS: This is one of the first studies to examine peer
      substance use as a mediator of pubertal timing and adolescent substance use using
      a longitudinal design. Early maturing males are at equal risk to early maturing
      females for interacting with peers that may draw them into substance use.
      Additionally, the findings indicate that while peers are mediators for comparison
      adolescents a different mechanism may link early puberty to substance use for
      maltreated adolescents.

PMID- 22609061
TI  - Co-ingestion of prescription opioids and other drugs among high school seniors:
      results from a national study.
AB  - BACKGROUND: The objective of this study was to determine the past-year prevalence
      rates and behavioral correlates of co-ingestion of prescription opioids and other
      drugs among high school seniors in the United States. METHODS: Nationally
      representative probability samples of high school seniors in the United States
      were surveyed as a part of the Monitoring the Future (MTF) study. Data were
      collected in schools via self-administered paper-and-pencil questionnaires during
      the spring of each cohort's senior year. The sample consisted of five cohorts
      (senior years of 2002-2006) made up of 12,441 high school seniors (modal age 18),
      of which 53% were women. RESULTS: The estimated prevalence of any past-year co
      ingestion of prescription opioids and other drugs for these cohorts was 4.4%, and
      69.8% among nonmedical users of prescription opioids. The substances most
      commonly co-ingested with prescription opioids included marijuana (58.5%),
      alcohol (52.1%), cocaine (10.6%), tranquilizers (10.3%), and amphetamines (9.5%).
      Nonmedical users who co-ingested prescription opioids with other drugs were more
      likely to report intranasal administration, recreational motives, oxycodone use,
      and greater subjective high when using prescription opioids than nonmedical users
      who did not co-ingest prescription opioids and other drugs. CONCLUSIONS: Nearly 7
      out of every 10 nonmedical users of prescription opioids reported co-ingestion of
      prescription opioids and other drugs in the past year. The findings indicate that
      the co-ingestion of prescription opioids and other drugs by high school seniors
      in the United States serves as a marker for substance abuse and represents a
      significant public health concern.

PMID- 22609063
TI  - Development and application of a portable manual non-contact-type goniometric
      instrument for measuring human anatomical angular parameters.
AB  - Several manual contact-type goniometric instruments have previously been
      developed to measure joint range of motion (ROM) during physical-therapy
      evaluation. These include the universal goniometer and the gravity-dependent
      goniometer, or inclinometer, which are used to measure the ROM angle of a subject
      in a fully erect posture. Here, we developed a manual non-contact-type portable
      goniometric instrument for the measurement of anatomical angular parameters based
      on the principle of spot irradiation by using laser markers. The accuracy of the
      developed instrument was tested and its performance was compared with that of a
      contact-type instrument by using a skeletal model (14 static angle assessments),
      a free posture manikin (18 static angle assessments), and healthy human bodies (5
      males and 5 females; 11 dynamic angle assessments). Measurement errors were
      examined also. When taking the measurements, a visual landmark-detection method
      was used in place of the conventional palpation method, which is inappropriate
      for a non-contact measuring system. The instrument developed here is applicable
      for practical non-contact goniometry and ROM measurements.

PMID- 22609062
TI  - Tetraspanin-interacting protein IGSF8 is dispensable for mouse fertility.
AB  - OBJECTIVE: To determine the physiological role of IGSF8 for fertility. DESIGN:
      Experimental prospective study. SETTING: Academic basic research laboratory.
      ANIMAL(S): C57BL/6J and hybrid B6D2F1 mice, as well as Cd9 and Igsf8 knockout
      mice (C57BL/6J and 129/SvJ mix background), were used for this study.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): In vitro and in vivo fertility
      tests of Igsf8 knockout mice. RESULT(S): Tetraspanin family member CD9 plays an
      important role in sperm-egg fusion. Recently, some researchers have reported that
      CD9 tightly associates with the immunoglobulin superfamily member IGSF8 on the
      egg surface and that IGSF8 is undetectable on the surface of Cd9-deficient eggs.
      This led us to hypothesize that IGSF8 participates in sperm-egg fusion together
      with CD9. To examine the physiological role of IGSF8 in vivo, we generated Igsf8
      deficient mice by homologous recombination and examined the fertility of the
      females. CONCLUSION(S): The Igsf8-deficient female mice showed no fertilization
      defect in vitro or in vivo. We observed that Igsf8-deficient eggs retained the
      normal level and localization of CD9, resulting in normal microvilli formation,
      which indicates that IGSF8 is dispensable in fertility.

PMID- 22609064
TI  - Transcriptional regulation of human-specific SVAF1 retrotransposons by cis
      regulatory MAST2 sequences.
AB  - SVA elements represent the youngest family of hominid non-LTR retrotransposons.
      Recently, a human-specific subfamily (termed SVA(F1), CpG-SVA, or MAST2-SVA) was
      discovered representing fusion of the CpG island-containing exon 1 of the MAST2
      gene and a 5'-truncated SVA. SVA(F1) includes at least 84 members, which suggests
      exceptionally high retrotransposition level. We investigated if the acquirement
      of the MAST2 CpG-island might play a role in the success of the SVA(F1)
      subfamily. We observed that in 16 samples representing seven human tissues, MAST2
      was cotranscribed with the members of the SVA(F1) subfamily, but not with other
      retrotransposons. We found that the methylation status of the MAST2-derived
      sequences of SVA(F1) elements reversely correlates with the transcriptional
      activity of MAST2. The MAST2 sequence at the 5' end of SVA(F1) acts as a positive
      transcriptional regulator in human germ cells. Finally, in various testicular
      tissue samples we uncovered a transcriptional correlation of MAST2 with the human
      L1, Alu and SVA retrotransposons.

PMID- 22609065
TI  - Depressive symptoms in adolescents with early and continuously treated
      phenylketonuria: associations with phenylalanine and tyrosine levels.
AB  - BACKGROUND: Previous research has suggested an increased risk for individuals
      with phenylketonuria (PKU) of developing depression and other mood disorders. As
      PKU can disrupt neurotransmitter synthesis via biochemical mechanisms, depressive
      symptoms are hypothesised to result from neurotransmitter dysregulation. Whilst
      adherence (or return) to the phenylalanine-restricted diet may resolve or improve
      symptoms of depression, data to demonstrate a direct relationship between
      biochemistry and mood in this population are lacking. METHODS: Thirteen
      adolescents with early and continuously treated PKU and eight sibling controls
      were compared in their total reported depressive symptoms. A general executive
      function assessment was also undertaken in the PKU group. Correlations between
      depressive symptoms and biochemical markers were examined within the PKU group
      only. RESULTS: Correlational analyses within the PKU group demonstrated strong
      and significant associations between depressive symptoms and long term exposure
      to either a high phenylalanine:tyrosine ratio, or low tyrosine. Increasing
      symptoms of depression were also found to be associated with poorer executive
      function in the PKU sample. However, both groups of adolescents scored within the
      normal range in symptoms of depression (p>0.05). CONCLUSIONS: Significant
      associations were observed between biochemical markers indicating poorer dietary
      control and increasing depressive symptoms in a sample of adolescents with early
      and continuously treated PKU, although symptoms of depression remained within the
      normal range. An association between depressive symptoms and poorer EF was also
      demonstrated. Further research is needed to establish whether the depressive
      symptoms observed in this young population represent an emerging (subclinical)
      risk for major depressive disorder as they age.

PMID- 22609066
TI  - AntR-mediated bidirectional activation of antA and antR, anthranilate degradative
      genes in Pseudomonas aeruginosa.
AB  - Bidirectional activation of transcription is a peculiar regulation mode of gene
      expression. In this study, we show that genes involved in the metabolism of
      anthranilate, a precursor of biosynthesis of tryptophan and Pseudomonas quinolone
      signal (PQS) are regulated by this bidirectional activation of transcription.
      Anthranilate is degraded by anthranilate dioxygenase complex encoded by antABC
      operon, and AntR, a LysR-type regulator encoded by antR activates the
      transcription of antABC operon in the presence of anthranilate. In P. aeruginosa,
      antABC and antR are divergently located and AntR binds to the intergenic region
      between antA and antR to activate the antABC transcription. In this study, we
      determined the transcriptional start site of the antA promoter (antA(p)) and AntR
      responsive elements (AREs) in P. aeruginosa. The upstream deletion analysis of
      antA(p) and in vitro gel shift assay with purified AntR showed that there are two
      AREs at -194 to -148 and -88 to -47 regions. We also found that AntR activates
      antR promoter (antR(p)) in the opposite direction and both AREs are important in
      the bidirectional activation of antA(p) and antR(p). Two AREs have different
      binding affinities to AntR and the strength of transcriptional activation was
      dramatically asymmetric depending on the direction. We suggest that the different
      affinities of two AREs may explain the asymmetry of the bidirectional activation
      by AntR.

PMID- 22609068
TI  - Obesity, expiratory flow limitation and asthma symptoms.
AB  - Obesity is associated with poor asthma control, but the reason for this is
      unclear. Reduction in operating lung volume, as occurs in obesity, and
      bronchoconstriction, as occurs in asthma, can increase expiratory flow limitation
      during tidal breathing (EFLt), which may in turn increase respiratory symptoms.
      The aim of this study was to determine the effect of obesity on EFLt at baseline
      and after bronchoconstriction in non-asthmatic and asthmatic subjects, and to
      determine the association between EFLt, and respiratory symptoms. Data from
      previously published studies in non-asthmatic and asthmatic subjects were
      reanalyzed using an index of EFLt derived from respiratory system reactance
      measured by the forced oscillation technique. The analysis showed that during
      bronchoconstriction both non-asthmatic and asthmatic obese individuals were more
      likely to develop EFLt than non-obese subjects, despite similar changes in FEV1.
      Furthermore the index of EFLt was a significant determinant of the severity of
      breathlessness during challenge in non-asthmatic subjects, and of asthma symptom
      control in asthmatic subjects following anti-inflammatory treatment. These
      studies suggest that the combination of bronchoconstriction and low resting lung
      volume increase the risk of EFLt, and that this altered response to
      bronchoconstriction may increase the severity of symptoms and lead to worse
      asthma control.

PMID- 22609067
TI  - Effects of obesity and weight loss on airway physiology and inflammation in
      asthma.
AB  - Obesity is a major risk factor for asthma, but the mechanisms for the development
      of asthma in the setting of obesity are not known. The purpose of this article is
      to review the effects of obesity on airway inflammation in patients with asthma,
      and to discuss the effects of obesity on airway reactivity in patients with
      asthma. Obesity is particularly a risk factor for non-atopic asthma. Airway
      eosinophilic inflammation is not increased in obesity, in fact the preponderance
      of the evidence suggests that airway eosinophilia is decreased in obesity. There
      is some preliminary data suggesting that airway neutrophilia may be increased in
      obesity, and that this may be particularly related to dietary fats. Obesity also
      alters adaptive immunity, and may suppress lymphocyte function typically
      associated with asthmatic airway inflammation. Population based studies are
      somewhat inconsistent on the relationship between airway reactivity and asthma,
      however, recent studies in bariatric surgery show that weight loss surgery in
      severely obese patients decreases airway reactivity. One study suggested that
      this was particularly the case for those with low IgE (a marker of a low TH2
      asthma phenotype), suggesting there may be some heterogeneity in asthma in
      obesity. There are likely to be two phenotypes of asthma in the obese: one group
      with early onset disease and asthma complicated by obesity, and a 2nd group with
      late onset disease with asthma consequent to obesity. Obesity leads to profound
      changes in airway function, and adaptive and innate immune responses which alter
      the nature of pre-existing allergic airway disease, and also cause new onset
      asthmatic disease.

PMID- 22609069
TI  - Altered levels of the Taraxacum kok-saghyz (Russian dandelion) small rubber
      particle protein, TkSRPP3, result in qualitative and quantitative changes in
      rubber metabolism.
AB  - Several proteins have been identified and implicated in natural rubber
      biosynthesis, one of which, the small rubber particle protein (SRPP), was
      originally identified in Hevea brasiliensis as an abundant protein associated
      with cytosolic vesicles known as rubber particles. While previous in vitro
      studies suggest that SRPP plays a role in rubber biosynthesis, in vivo evidence
      is lacking to support this hypothesis. To address this issue, a transgene
      approach was taken in Taraxacum kok-saghyz (Russian dandelion or Tk) to determine
      if altered SRPP levels would influence rubber biosynthesis. Three dandelion SRPPs
      were found to be highly abundant on dandelion rubber particles. The most abundant
      particle associated SRPP, TkSRPP3, showed temporal and spatial patterns of
      expression consistent with patterns of natural rubber accumulation in dandelion.
      To confirm its role in rubber biosynthesis, TkSRPP3 expression was altered in
      Russian dandelion using over-expression and RNAi methods. While TkSRPP3 over
      expressing lines had slightly higher levels of rubber in their roots, relative to
      the control, TkSRPP3 RNAi lines showed significant decreases in root rubber
      content and produced dramatically lower molecular weight rubber than the control
      line. Not only do results here provide in vivo evidence of TkSRPP proteins
      affecting the amount of rubber in dandelion root, but they also suggest a
      function in regulating the molecular weight of the cis-1, 4-polyisoprene polymer.

PMID- 22609070
TI  - Texture and satiation: the role of oro-sensory exposure time.
AB  - One of the characteristics of the current obesogenic food supply is the large
      availability of foods that can be ingested quickly. Controlled nutrition
      intervention studies have shown that the ingestion of simple energy containing
      beverages, which are consumed very quickly, do not lead to a lower compensatory
      intake of other foods. One of the theories behind this observation is that
      calories that are ingested quickly are not well sensed by the sense of taste, and
      do not lead to an adequate satiety response. This idea is confirmed by the
      results of a series of studies, where we have shown that the low
      satiation/satiety response of beverages can be largely attributed to their short
      oral residence time. Prolonging the oro-sensory exposure time to foods leads to
      earlier meal termination and/or a higher satiety response. The low
      satiation/satiety response to simple energy containing beverages is congruent
      with the observation from studies on the cephalic phase response to foods, i.e.
      the physiological response to sensory signals. Energy containing beverages do not
      lead to an adequate cephalic phase response. Various recent studies showed that
      slower eating leads to higher levels of satiety hormones. These results are in
      line with the idea that the sense of taste is a nutrient sensor which informs the
      brain and the gut about the inflow of nutrients. The sense of taste has an
      important contribution to the satiating effect of foods. One of the challenges in
      future research is to see whether or not these proofs of principles can be
      applied in longer term studies with regular commercial foods. This may make our
      obesogenic food supply more satiating, and may lead to a lower energy intake.

PMID- 22609071
TI  - The mosaic flap for single-stage reconstruction of nasal ala defects.

PMID- 22609072
TI  - Physical and psychological maltreatment in childhood and later health problems in
      women: an exploratory investigation of the roles of perceived stress and coping
      strategies.
AB  - OBJECTIVE: This retrospective, cross-sectional study investigated the association
      between childhood physical and psychological maltreatment and self-reported
      physical health concerns in adult women. The mediating roles of perceived stress
      and coping strategies were examined. METHODS: Participants were 235 women (aged
      18-59 years) recruited from the community. Semi-structured interviews and
      questionnaires were used to assess self-reported childhood maltreatment and
      current perceived stress, coping strategies, and health status. Data were
      analyzed using structural equation modeling. RESULTS: After controlling for a
      history of child sexual abuse and relevant demographic variables, child physical
      and psychological maltreatment were significantly associated with greater
      physical health concerns. Support was found for models in which perceived stress
      and emotion-focused coping partially mediate the relation between maltreatment
      and health problems; problem-focused and avoidance coping did not operate as
      mediators. Multi-mediation model testing indicated that emotion-focused coping
      and perceived stress together better explain the relationship between child
      maltreatment and physical health than either variable alone. CONCLUSION: Findings
      suggest that child maltreatment is an important risk factor for adverse health
      outcomes in later life and that current stress and coping strategies may
      influence this relationship. Implications for the physical health of maltreatment
      survivors are discussed. PRACTICE IMPLICATIONS: The management of perceived
      stress and the use of adaptive emotion-focused coping responses in the everyday
      lives of maltreated women may be particularly useful points of intervention in
      order to mitigate physical health concerns in adulthood.

PMID- 22609073
TI  - Termination of the structural confusion between plipastatin A1 and fengycin IX.
AB  - Plipastatin A1 and fengycin IX were experimentally proven to be identical
      compounds, while these had been considered as diastereomers due to the
      permutation of the enantiomeric pair of Tyr in most papers. The (1)H NMR spectrum
      changed to become quite similar to that of plipastatin A1, when the sample which
      provided resembled spectrum of fengycin IX was treated with KOAc followed by LH
      20 gel filtration. Our structural investigations disclosed that the structures of
      these molecules should be settled into that of plipastatin A1 by Umezawa (L-Tyr4
      and D-Tyr10).

PMID- 22609074
TI  - Synthesis and evaluation of N(1)-alkylindole-3-ylalkylammonium compounds as
      nicotinic acetylcholine receptor ligands.
AB  - In this study thirty-three novel indole derivatives were designed and synthesized
      based on the structure of deformylflustrabromine B (1), a metabolite isolated
      from the marine bryozoan Flustra foliacea L. The syntheses were carried out using
      standard methodologies and in good yields. The molecules were tested for their
      affinities for the alpha4beta2(*), alpha3beta4(*), alpha7(*) and
      (alpha1)(2)beta1gammadelta nicotinic acetylcholine receptor (nAChR) subtypes.
      Binding assays showed that, among these ligands, compound 7c exhibited the
      highest affinity with K(i)=136.1, 93.9 and 862.4nM for the alpha4beta2(*),
      alpha3beta4(*), and alpha7(*) nAChRs subtypes, respectively. These results
      indicated that the indole core might be a useful scaffold for the development of
      new potent and selective nAChR ligands.

PMID- 22609075
TI  - Supercooled aqueous nuclear magnetic resonance using agarose gels.
AB  - Low-temperature nuclear magnetic resonance (NMR), especially under supercooled
      conditions, can give critical insight into biomolecular systems via slowed
      dynamics and exchange rates. These conditions can also increase correlation times
      of small molecules, potentially allowing for NMR structural study of small
      molecules at moderate field strengths. Agarose gels allow for supercooled
      conditions and are simple to prepare, invisible to NMR, and noninteractive with
      most biomolecules and organics. Here we demonstrate their use with nucleic acids,
      small organic molecules, and peptides.

PMID- 22609077
TI  - Extracorporeal membrane oxygenation support in a situation of diagnostic dilemma.
AB  - Severe acute respiratory distress syndrome (ARDS) in children carries a high
      morbidity and mortality. High frequency ventilation and extracorporeal membrane
      oxygenation (ECMO) are used as rescue modes of support in difficult situations.
      Malignancy may be considered to be a relative contraindication to ECMO support.
      We report a case where the decision was made to support the patient with ECMO for
      fulminant Epstein-Barr (EBV) infection while investigations were being done to
      exclude an underlying malignancy.

PMID- 22609076
TI  - Analysis of glycosaminoglycan-derived disaccharides by capillary electrophoresis
      using laser-induced fluorescence detection.
AB  - A quantitative and highly sensitive method for the analysis of glycosaminoglycan
      (GAG)-derived disaccharides that relies on capillary electrophoresis (CE) with
      laser-induced fluorescence detection is presented. This method enables complete
      separation of 17 GAG-derived disaccharides in a single run. Unsaturated
      disaccharides were derivatized with 2-aminoacridone to improve sensitivity. The
      limit of detection was at the attomole level and approximately 100-fold more
      sensitive than traditional CE-ultraviolet detection. A CE separation timetable
      was developed to achieve complete resolution and shorten analysis time. The
      relative standard deviations of migration time and peak areas at both low and
      high concentrations of unsaturated disaccharides are all less than 2.7 and 3.2%,
      respectively, demonstrating that this is a reproducible method. This analysis was
      successfully applied to cultured Chinese hamster ovary cell samples for
      determination of GAG disaccharides. The current method simplifies GAG extraction
      steps and reduces inaccuracy in calculating ratios of heparin/heparan sulfate to
      chondroitin sulfate/dermatan sulfate resulting from the separate analyses of a
      single sample.

PMID- 22609078
TI  - The role of cardiac computed tomography in assessment of acute chest pain.

PMID- 22609079
TI  - Ligation of intersphincteric fistula tract compared with advancement flap for
      complex anorectal fistulas requiring initial seton drainage.
AB  - BACKGROUND: The ligation of intersphincteric fistula tract (LIFT) is a relatively
      new surgical technique for treating complex anorectal fistulas. METHODS: LIFT was
      compared with anorectal advancement flap management (ARAF) of complex anorectal
      fistulas requiring previous seton drainage. Crohn's patients were excluded.
      Patients with no confirmed recurrent sepsis after 6 months were randomized to day
      surgery performance of LIFT (25; 17 male) or ARAF (14; 10 male) with removal of
      the seton. Outcome measures included recurrences, surgical time, complications,
      hospital readmissions, and fecal incontinence. RESULTS: LIFT was 32.5 minutes
      shorter than ARAF (P < .001). Complications were similar, with no hospital
      readmissions. Return to normal activities was 1 week for LIFT patients, 2 weeks
      for ARAF patients (P = .016). At 19 months there were 3 recurrences (2 in the
      LIFT group). One ARAF patient had minor incontinence. CONCLUSIONS: The LIFT
      procedure was simple, safe, shorter, and patients returned to work earlier. All
      patients had preliminary seton drainage, possibly contributing to the low
      recurrence rates.

PMID- 22609080
TI  - Proximal femoral diaphyseal cross-sectional geometry in Orrorin tugenensis.
AB  - Functional adaptations in femora attributed to Orrorin tugenensis provide a
      unique opportunity to examine locomotor behavior very early in the hominin
      lineage. This study examines relative cortical thickness, cortical area (CA)
      relative to the polar moment of area (J), and J relative to femoral head
      superoinferior diameter (FHD) in the proximal femur of O. tugenensis (BAR 1002'00
      and BAR 1003'00), and compares patterns in this early hominin with those in a
      sample of modern humans (N=31), Plio-Pleistocene fossil hominins (N=8), Pan
      troglodytes troglodytes (N=13), and Pan paniscus (N=3). Relative cortical
      thickness and CA relative to J in the proximal femur of O. tugenensis are
      comparable to patterns generally found in other fossil hominins. Proximal femoral
      diaphyseal J relative to FHD in BAR 1002'00 is similar to patterns found in
      fossil hominins typically attributed to a non-Homo genus (i.e. SK 82, SK 97, and
      KNM-ER 738). Cross-sectional geometric patterns in the proximal femur of Orrorin
      are not unlike those generally found in australopithecines and fossil Homo. While
      the results of this study cannot confirm unequivocally that Orrorin was an
      obligate biped, a mode of locomotion comparable to that proposed for
      australopithecines cannot be ruled out.

PMID- 22609082
TI  - Traditional neuropsychological correlates and reliability of the automated
      neuropsychological assessment metrics-4 battery for Parkinson's disease.
AB  - BACKGROUND: The automated neuropsychological assessment metrics battery-4 for PD
      offers the promise of a computerized approach to cognitive assessment. METHODS:
      To assess its utility, the ANAM4-PD was administered to 72 PD patients and 24
      controls along with a traditional battery. Reliability was assessed by retesting
      26 patients. RESULTS: The cognitive efficiency score (CES; a global score)
      exhibited high reliability (r = 0.86). Constituent variables exhibited lower
      reliability. The CES correlated strongly with the traditional battery global
      score, but displayed weaker relationships to UPDRS scores than the traditional
      score. Multivariate analysis of variance revealed a significant difference
      between the patient and control groups in ANAM4-PD performance, with three ANAM4
      PD tests, math, tower, and pursuit tracking, displaying sizeable differences. In
      discriminant analyses these variables were as effective as the total ANAM4-PD in
      classifying cases designated as impaired based on traditional variables.
      Principal components analyses uncovered fewer factors in the ANAM4-PD relative to
      the traditional battery. ANAM4-PD variables correlated at higher levels with
      traditional motor and processing speed variables than with untimed executive,
      intellectual or memory variables. CONCLUSIONS: The ANAM4-PD displays high global
      reliability, but variable subtest reliability. The battery assesses a narrower
      range of cognitive functions than traditional tests, and discriminates between
      patients and controls less effectively. Three ANAM4-PD tests, pursuit tracking,
      math, and tower performed as well as the total ANAM4-PD in classifying patients
      as cognitively impaired. These findings could guide the refinement of the ANAM4
      PD as an efficient method of screening for mild to moderate cognitive deficits in
      PD patients.

PMID- 22609083
TI  - Stereopsis and binocular rivalry are based on perceived rather than physical
      orientations.
AB  - Binocular rivalry is an intriguing phenomenon: when different images are
      displayed to the two eyes, perception alternates between these two images. What
      determines whether two monocular images engage in fusion or in rivalry: the
      physical difference between these images or the difference between the percepts
      resulting from the images? We investigated that question by measuring the
      interocular difference of grid orientation needed to produce a transition from
      fusion to rivalry and by changing those transitions by means of a superimposed
      tilt illusion. Fusion was attested by a correct stereoscopic slant perception of
      the grid. The superimposed tilt illusion was achieved in displaying small
      segments on the grids. We found that the illusion can change the fusion-rivalry
      transitions indicating that rivalry and fusion are based on the perceived
      orientations rather than the displayed ones. In a second experiment, we confirmed
      that the absence of binocular rivalry resulted in fusion and stereoscopic slant
      perception. We conclude that the superimposed tilt illusion arises at a level of
      visual processing prior to those stages mediating binocular rivalry and
      stereoscopic depth extraction.

PMID- 22609081
TI  - Bone marrow-CNS connections: implications in the pathogenesis of diabetic
      retinopathy.
AB  - Diabetic retinopathy is the fourth most common cause of blindness in adults.
      Current therapies, including anti-VEGF therapy, have partial efficacy in
      arresting the progression of proliferative diabetic retinopathy and diabetic
      macular edema. This review provides an overview of a novel, innovative approach
      to viewing diabetic retinopathy as the result of an inflammatory cycle that
      affects the bone marrow (BM) and the central and sympathetic nervous systems.
      Diabetes associated inflammation may be the result of BM neuropathy which skews
      haematopoiesis towards generation of increased inflammatory cells but also
      reduces production of endothelial progenitor cells responsible for maintaining
      healthy endothelial function and renewal. The resulting systemic inflammation
      further impacts the hypothalamus, promoting insulin resistance and diabetes, and
      initiates an inflammatory cascade that adversely impacts both macrovascular and
      microvascular complications, including diabetic retinopathy (DR). This review
      examines the idea of using anti-inflammatory agents that cross not only the blood
      retinal barrier to enter the retina but also have the capability to target the
      central nervous system and cross the blood-brain barrier to reduce
      neuroinflammation. This neuroinflammation in key sympathetic centers serves to
      not only perpetuate BM pathology but promote insulin resistance which is
      characteristic of type 2 diabetic patients (T2D) but is also seen in T1D. A case
      series of morbidly obese T2D patients with retinopathy and neuropathy treated
      with minocycline, a well-tolerated antibiotic that crosses both the blood-retina
      and blood-brain barrier is presented. Our results indicates that minocycine shows
      promise for improving visual acuity, reducing pain from peripheral neuropathy,
      promoting weight loss and improving blood pressure control and we postulate that
      these observed beneficial effects are due to a reduction of chronic inflammation.

PMID- 22609084
TI  - Physician density in a two-tiered health care system.
AB  - We investigate the density of non-contract (private) physicians in a two-tiered
      health care system, i.e., one with co-existing public and private health care
      providers. In particular, we analyze how the densities of private and public
      suppliers of outpatient health care (general practitioners and specialists) are
      related to each other. Using a panel of 121 Austrian districts between 2002 and
      2008, we apply a Hausman-Taylor estimator, which allows to treat each of these
      densities as endogenous. We find that the density of non-contract specialists is
      positively associated with the density of non-contract general practitioners, but
      not significantly related to the density of contract general practitioners. We
      also observe a negative relationship between the densities of non-contract and
      contract general practitioners and the ones of non-contract and contract
      specialists, indicating competitive forces between the private and the public
      sector of the outpatient health care provision in Austria. Our results contribute
      to the ongoing debate on the role of non-contract physicians for health care
      provision in Austria.

PMID- 22609085
TI  - Immigrant status and cognitive functioning in late-life: an examination of gender
      variations in the healthy immigrant effect.
AB  - Although some research suggests that the healthy immigrant effect extends to
      cognitive functioning, it is unclear whether this general pattern varies
      according to gender. We use six waves of data collected from the original cohort
      of the Hispanic Established Populations for the Epidemiologic Study of the
      Elderly to estimate a series of linear growth curve models to assess variations
      in cognitive functioning trajectories by nativity status and age at migration to
      the U.S.A. among women and men. Our results show, among women and men, no
      differences in baseline cognitive status (intercepts) between early- (before age
      20) and late-life (50 and older) immigrants and U.S.-born individuals of Mexican
      origin. We also find, among women and men, that middle-life (between the ages of
      20 and 49) immigrants tend to exhibit higher levels of baseline cognitive
      functioning than the U.S.-born. Our growth curve analyses suggest that the
      cognitive functioning trajectories (slopes) of women do not vary according to
      nativity status and age at migration. The cognitive functioning trajectories of
      early- and late-life immigrant men are also similar to those of U.S.-born men;
      however, those men who migrated in middle-life tend to exhibit slower rates of
      cognitive decline. A statistically significant interaction term suggests that the
      pattern for middle-life migration is more pronounced for men (or attenuated for
      women). In other words, although women and men who migrated in middle-life
      exhibit higher levels of baseline cognitive functioning, immigrant men tend to
      maintain this advantage for a longer period of time. Taken together, these
      patterns confirm that gender is an important conditioning factor in the
      association between immigrant status and cognitive functioning.

PMID- 22609086
TI  - Improper disclosure: tobacco packaging and emission labelling regulations.
AB  - OBJECTIVES: Cigarette packets in many countries display emission numbers such as
      tar. These numbers may be misleading as they do not represent the amount of
      toxins delivered to human smokers. This study examined how consumers interpret
      and understand numerical and descriptive emission information. STUDY DESIGN: A
      discrete choice study was conducted among adult smokers (n = 312) and non-smokers
      (n = 291) in Ontario, Canada. METHODS: Participants viewed groups of cigarette
      packets with emission labels from the European Union (EU), Canada and Australia.
      Participants completed ratings on perceived tar delivery, health risks, and
      usefulness and understandability of the information. RESULTS: Participants were
      significantly more likely to believe that Canadian and EU packets with lower
      emission numbers would have lower tar delivery (92.2% and 89.9%, respectively)
      and lower health risks (89.5% and 82.9%, respectively) than packets with higher
      numbers. Approximately 74% of participants rated the numerical Canadian label as
      providing the most useful information; however, 62% also rated this label as most
      difficult to understand. Most participants rated the descriptive Australian label
      as easiest to understand. CONCLUSIONS: Labels featuring quantitative emission
      values are associated with false beliefs regarding lower tar delivery and health
      risks. Descriptive statements about emissions are easier to understand and
      associated with more accurate beliefs.

PMID- 22609087
TI  - Iron metabolism in hepcidin1 knockout mice in response to phenylhydrazine-induced
      hemolysis.
AB  - Hepcidin, an iron regulatory peptide, plays a central role in the maintenance of
      systemic iron homeostasis by inducing the internalization and degradation of the
      iron exporter, ferroportin. Hepcidin expression in the liver is regulated in
      response to several stimuli including iron status, erythropoietic activity,
      hypoxia and inflammation. Hepcidin expression has been shown to be reduced in
      phenylhydrazine-treated mice, a mouse model of acute hemolysis. In this mouse
      model, hepcidin suppression was associated with increased expression of molecules
      involved in iron transport and recycling. The present study aims to explore
      whether the response to phenylhydrazine treatment is affected by hepcidin
      deficiency and/or the subsequently altered iron metabolism. Hepcidin1 knockout
      (Hamp(-/-)) and wild type mice were treated with phenylhydrazine or saline and
      parameters of iron homeostasis were determined 3 days after the treatment. In
      wild type mice, phenylhydrazine administration resulted in significantly reduced
      serum iron, increased tissue non-heme iron levels and suppressed hepcidin
      expression. The treatment was also associated with increases in membrane
      ferroportin protein levels and spleen heme oxygenase 1 mRNA expression. In
      addition, trends toward increased mRNA expression of duodenal iron transporters
      were also observed. In contrast, serum iron and tissue non-heme iron levels in
      Hamp(-/-) mice were unaffected by the treatment. Moreover, the effects of
      phenylhydrazine on the expression of ferroportin and duodenal iron transporters
      were not observed in Hamp(-/-) mice. Interestingly, mRNA levels of molecules
      involved in splenic heme uptake and degradation were significantly induced by
      Hamp disruption. In summary, our study demonstrates that the response to
      phenylhydrazine-induced hemolysis differs between wild type and Hamp(-/-) mice.
      This observation may be caused by the absence of hepcidin per se or the altered
      iron homeostasis induced by the lack of hepcidin in these mice.

PMID- 22609088
TI  - Aortopulmonary window characterized with two- and three-dimensional
      echocardiogram in a dog.
AB  - Aortopulmonary window is a rare congenital anomaly, resulting from incomplete
      septation of the truncus arteriosus into the aorta and the pulmonary artery
      during embryogenesis. The utility of three-dimensional (3D) echocardiogram has
      not been previously reported in dogs with aortopulmonary windows. The authors
      demonstrate the diagnostic potentials of 3D echocardiogram and its ability to
      more completely define the anatomical features of aortopulmonary window in a dog
      when compared to two-dimensional imaging. Ultimately 3D echocardiogram was
      considered to provide information critical to determining the feasibility of
      beating heart surgical correction in this case.

PMID- 22609089
TI  - A cardiac vascular hamartoma in a calf: ultrasonographic and pathologic images.
AB  - A right atrial mass was observed by ultrasound in a 3-month-old red Holstein
      calf. Differential diagnoses included endocarditis or tumor. Due to the poor
      prognosis, the calf was euthanized. On gross examination, there was a marked
      dilation of the right atrium. A round, poorly delineated, 2 cm mass was
      visualized in the right atrium. Microscopic findings were consistent with a
      vascular hamartoma.

PMID- 22609090
TI  - Administration of a vaccine composed of dendritic cells pulsed with premalignant
      oral lesion lysate to mice bearing carcinogen-induced premalignant oral lesions
      stimulates a protective immune response.
AB  - The use of dendritic cell (DC) vaccines as treatment for malignancy is
      complicated by immune evasion tactics often employed by carcinomas such as head
      and neck squamous cell carcinoma (HNSCC). The present study aims to determine if
      an immune response can be elicited by administering a DC vaccine during the
      premalignant stages of HNSCC, prior to development of immune escape. Mice treated
      with the carcinogen 4-nitroquinoline 1-oxide (4NQO) in drinking water develop
      premalignant oral lesions that progress to HNSCC. As previous studies
      demonstrated that premalignant lesions and HNSCC overexpress common tumor
      antigens, bone marrow-derived DCs were pulsed with premalignant lesion lysate
      (DCpm) and administered to 4NQO-treated mice exhibiting premalignant lesions.
      Lesion progression was tracked through endoscopy, which revealed that DCpm
      vaccination and control vaccination with dendritic cells pulsed with normal
      tongue epithelium lysate (DCnt) significantly decreased lesion burden at 8weeks.
      Analysis of lymph node cells revealed that while DCnt vaccination resulted in a
      rapid increase in total lymphocyte count, levels of activated conventional CD4(+)
      T cells and Th1, Tc1, Th17, Tc17, and Th2 cells, DCpm vaccination results in a
      delayed, yet substantial, increase in these immune effector mechanisms. This
      suggests that dendritic cell vaccination may have a beneficial effect on clinical
      outcome regardless of type of antigenic stimulation. Also, pulsing DCs with
      premalignant lysate rather than normal tongue epithelium lysate affects the
      dendritic cells in a way that delays the immune effector response upon
      vaccination of premalignant lesion-bearing mice.

PMID- 22609091
TI  - bFGF inhibits ER stress induced by ischemic oxidative injury via activation of
      the PI3K/Akt and ERK1/2 pathways.
AB  - Extensive research has focused on finding effective strategies to prevent or
      improve recovery from brain ischemia and reperfusion (I/R) injury. The basic
      fibroblast growth factor (bFGF) has been shown to have therapeutic potential in
      some central nervous system (CNS) disorders, including ischemic injury. In this
      study, we demonstrate that bFGF administration can improve locomotor activity and
      inhibit the ER stress induced in the CA1 region of the hippocampus in a mouse
      model of I/R injury. In vitro, bFGF exerts a protective effect by inhibiting the
      ER stress response proteins CHOP, XBP-1, ATF-6 and caspase-12 that are induced by
      H(2)O(2) treatment. Both of these in vivo and in vitro effects are related to the
      activation of two downstream signaling pathways, PI3K/Akt and ERK1/2. Inhibition
      of the PI3K/Akt and ERK1/2 pathways by specific inhibitors, LY294002 and U0126,
      respectively, partially reduce the protective effect of bFGF. Taken together, our
      results indicate that the neuroprotective role of bFGF involves the suppression
      of ER stress in the ischemic oxidative damage models and oxidative stress-induced
      PC12 cell injury, and these effects is underlying the activation of the PI3K/Akt
      and ERK1/2 signal pathway.

PMID- 22609092
TI  - Perfluorooctanoic acid affects the activity of the hepatocyte nuclear factor 4
      alpha (HNF4alpha).
AB  - Perfluorooctanoic acid (PFOA) is an industrial chemical that is a global
      contaminant of water, soil and foodstuff. Numerous animal studies have revealed
      that PFOA has embryotoxic and hepatotoxic effects in rodents. On the molecular
      level, the adverse effects of PFOA have been correlated with the PFOA-mediated
      activation of peroxisome proliferator-activated receptor alpha (PPARalpha),
      however, the toxicological relevance of this mode of action for humans is under
      debate. In this study, a proteomic approach was chosen to screen for molecular
      targets affected by PFOA in human liver cells. Treatment of the human liver cell
      line HepG2 with 25 MUM PFOA resulted in 51 deregulated proteins in a two
      dimensional gel experiment, and 36 of these proteins were identified by mass
      spectrometry. Network analysis revealed that these proteins are primarily
      involved in lipid metabolism and cancer. The hepatocyte nuclear factor 4alpha
      (HNF4alpha), but not PPARalpha, was the key regulator of the network. Indeed,
      subsequent western blot analysis revealed that the amount of HNF4alpha as well as
      of its target HNF1alpha was downregulated in PFOA-treated HepG2 cells. Moreover,
      PFOA was shown to inhibit HNF4alpha-dependent gene transcription. Thus, this
      study provides first experimental evidence that HNF4alpha is negatively affected
      by PFOA.

PMID- 22609094
TI  - Quantitative approaches to cancer stem cells and epithelial-mesenchymal
      transition.
AB  - The last decade has witnessed significant advances in the application of
      mathematical and computational models to biological systems, especially to cancer
      biology. Here, we present stochastic and deterministic models describing tumour
      growth based on the cancer stem cell hypothesis, and discuss the application of
      these models to the epithelial-mesenchymal transition. In particular, we discuss
      how such quantitative approaches can be used to validate different possible
      scenarios that can lead to an increase in stem cell activity following induction
      of epithelial-mesenchymal transition, observed in recent experimental studies on
      human breast cancer and related cell lines. The utility of comparing mammosphere
      data to computational mammosphere simulations in elucidating the growth
      characteristics of mammary (cancer) stem cells is discussed as well.

PMID- 22609093
TI  - Biological evaluation of Fe3O4-poly(L-lactide)-poly(ethylene glycol)-poly(L
      lactide) magnetic microspheres prepared in supercritical CO2.
AB  - The biocompatibility of Fe3O4-poly(L-lactide)-poly(ethylene glycol)-poly(L
      lactide) magnetic microspheres (Fe3O4-PLLA-PEG-PLLA MMPs) prepared in a process
      of suspension-enhanced dispersion by supercritical CO2 (SpEDS) was evaluated at
      various levels: cellular, molecular, and integrated. At the cellular level, the
      investigations of cytotoxicity and intracellular reactive oxygen species (ROS)
      generation indicate that the polymer-coated MMPs (2.0 mg/mL) had a higher
      toxicity than uncoated Fe3O4 nanoparticles, which led to about 20% loss of cell
      viability and an increase (0.2 fold) in ROS generation; the differences were not
      statistically significant (p > 0.05). However, an opposite phenomenon was
      observed in tests of hemolysis, which showed that the MMPs displayed the weakest
      hemolytic activity, namely only about 6% at the highest concentration (20 mg/mL).
      This phenomenon reveals that polymer-coated MMPs created less toxicity in red
      blood cells than uncoated Fe3O4 nanoparticles. At the molecular level, the MMPs
      were shown to be less genotoxic than Fe3O4 nanoparticles by measuring the
      micronucleus (MN) frequency in CHO-K1 cells. Furthermore, the mRNA expression of
      pro-inflammatory cytokines demonstrates that polymer-coated MMPs elicited a less
      intense secretion of pro-inflammatory cytokines than uncoated Fe3O4
      nanoparticles. Acute toxicity tests of MMPs show quite a low toxicity, with an
      LD50 > 1575.00 mg/kg. The evidence of low toxicity presented in the results
      indicates that the Fe3O4-PLLA-PEG-PLLA MMPs from the SpEDS process have great
      potential for use in biomedical applications.

PMID- 22609095
TI  - Orthodromic atrioventricular reciprocating tachycardia conducted with
      intraventricular conduction disturbance mimicking ventricular tachycardia in an
      English Bulldog.
AB  - Electrocardiographic tracings of an English Bulldog referred for cardiogenic
      shock due to an orthodromic atrioventricular reciprocating tachycardia conducted
      with intraventricular conduction disturbance and mimicking ventricular
      tachycardia (VT) are presented. At admission the surface ECG showed a wide QRS
      complex tachycardia (WCT) that was converted to sinus rhythm using manual
      cardioversion (chest thump). This change revealed pre-existing right bundle
      branch block, and a final diagnosis of supraventricular tachycardia (SVT) with
      intraventricular conduction disturbance was made. Electrophysiologic study
      defined the SVT mechanism as an atrioventricular macroreentrant tachycardia
      mediated by a single mid-septal accessory pathway. The differentiation between
      various types of WCT is essential when antiarrhythmic therapy is considered. The
      surface ECG should be systematically evaluated in order to recognize the
      characteristic features of SVT and VT. Moreover chest thump procedure can be very
      helpful in the attempt to convert the rhythm to sinus rhythm and to correctly
      recognize the underlying arrhythmia.

PMID- 22609096
TI  - Predictive value of global longitudinal strain in a surgical population of
      organic mitral regurgitation.
AB  - BACKGROUND: Because of the lack of reliable echocardiographic parameters to
      predict recovery after surgery, the optimal timing of surgery for severe mitral
      regurgitation remains controversial. The aim of this study was to determine
      whether global longitudinal strain (GLS) recorded preoperatively could help in
      predicting left ventricular (LV) ejection fraction (LVEF) postoperatively.
      METHODS: A total of 88 patients (mean age, 63 +/- 13 years; 59 men) with severe
      degenerative mitral regurgitation were included prospectively in this study. Rest
      echocardiography was performed before and 6 +/- 1 months after mitral valve
      surgery. Patients were divided into two groups: group A (postoperative LVEF >=
      50%) and group B (postoperative LVEF < 50%). RESULTS: In group B, patients had
      larger preoperative LV end-systolic diameters (21.6 +/- 2.6 vs 19.2 +/- 3.7
      mm/m(2), P = .02) and impaired preoperative GLS (-17 +/- 2.8% vs -19.6 +/- 3.6%,
      P = .01), whereas there was no difference in preoperative LVEF. Preoperative LV
      end-systolic diameter >= 22 mm/m(2) and GLS < -18% were independent predictors of
      postoperative LV dysfunction. CONCLUSIONS: LV end-systolic diameter is a well
      recognized prognostic marker. In addition, this study demonstrates the additive
      and independent predictive value of preoperative GLS for predicting postoperative
      LV dysfunction.

PMID- 22609097
TI  - Accuracy of fluoroscopic and electrocardiographic criteria for pacemaker lead
      implantation by comparison with three-dimensional echocardiography.
AB  - BACKGROUND: Fluoroscopic and electrocardiographic (ECG) criteria for the
      documentation of pacing lead positioning (apical and alternative sites) have been
      described, but data regarding their accuracy are lacking. METHODS: Fifty patients
      (27 men; mean age, 76 +/- 9 years) with permanent right ventricular (RV) pacing
      leads were included. RV lead position was classified as apical, mid septal, mid
      RV free wall, RV outflow tract (RVOT) septal, or RVOT free wall. Exact anatomic
      lead position was documented using three-dimensional (3D) transthoracic
      echocardiography (TTE). Cohen's kappa coefficient was used to assess agreement
      between fluoroscopic or ECG criteria and 3D TTE. RESULTS: True lead positions
      were as follows: 15 apical, 24 mid septal, three mid RV free wall, and eight RVOT
      septal wall; no leads were implanted into the RVOT free wall. Fluoroscopy (kappa
      = 0.56; 95% confidence interval [CI], 0.37-0.76) and electrocardiography (kappa =
      0.43; 95% CI, 0.25-0.60) had moderate overall agreement with 3D TTE. Fluoroscopy
      had moderate agreement with 3D TTE for apical (kappa = 0.57; 95% CI, 0.32-0.83),
      mid septal (kappa = 0.48; 95% CI, 0.25-0.72), and mid free wall sites (kappa =
      0.54; 95% CI, 0.08-1.00) and moderate to good agreement for the RVOT septal wall
      (kappa = 0.61; 95% CI, 0.30-0.90). Fluoroscopy misclassified as mid septal six of
      the 15 RV apical leads. ECG criteria had moderate agreement with 3D TTE for
      apical positions (kappa = 0.55; 95% CI, 0.34-0.77) and RVOT sites (kappa = 0.47;
      95% CI, 0.21-0.73). Electrocardiography misclassified as apical 10 and as RVOT
      six of the 24 mid septal leads. CONCLUSIONS: Fluoroscopic and ECG criteria are
      only moderately accurate in discriminating between RV apical, mid septal, mid
      free wall, and RVOT pacing sites. These data suggest that both fluoroscopy and
      electrocardiography may not be adequate techniques for the correct documentation
      of RV pacing lead position for routine clinical practice or research purposes.

PMID- 22609098
TI  - Grape seed extract attenuates lung parenchyma pathology in ovalbumin-induced
      mouse asthma model: an ultrastructural study.
AB  - Due to the growing incidence of asthma and because of the non-specificity and
      side effects of the conventional drugs, the development of novel agents for the
      treatment of asthma has become considerably important. Natural plant products
      offer promising alternatives for the development of effective and safe
      treatments. Grape seed extract (GSE) is one such phytochemical supplement that
      has been shown to have potent antioxidant and anti-inflammatory effects. Thus,
      the present study aimed to investigate the effect of GSE to suppress lung
      parenchyma pathology and inflammation in ovalbumin-induced murine asthma model.
      Ovalbumin exposure was associated with many pathological and morphometric
      alterations in the lungs of asthmatic mice. The alterations involved alveolar
      size reduction, alveolar wall thickening, cellular infiltration and blood
      capillary congestion, as well as significant increase in the number of type II
      pneumocytes and lamellar bodies. However, GSE significantly ameliorated of the
      pathological changes of ovalbumin-induced asthma. The results support the
      possibility of GSE as an effective, safe anti-inflammatory dietary supplement to
      attenuate the pathogenicity of asthma. While these preliminary results appear
      promising, further studies are required to elucidate the precise mechanism of the
      modulatory effect of GSE on asthma remodeling.

PMID- 22609099
TI  - Immobilisation and characterisation of the demineralised, fully hydrated organic
      matrix of nacre--an atomic force microscopy study.
AB  - Mimicry of the tough natural composite nacre in future bioengineering requires
      knowledge of the biomineralisation process. The insoluble organic matrix isolated
      from the shell of the gastropod Haliotis laevigata was characterised by protein
      chemistry, topographical and mechanical measurements. Demineralisation of nacre
      in dilute acetic acid or ethylenediaminetetraacetic acid revealed a set of
      soluble proteins and the insoluble matrix. The insoluble matrix contains a chitin
      core and firmly attached proteins, which could be removed by sodium dodecyl
      sulfate and glycerol indicating a hydrophobic interaction. Atomic force
      microscopy images of the native insoluble matrix showed a filamentous network
      with pores or holes, where the filaments showed globular attachments of different
      sizes, possibly the attached protein molecules. During direct observation of
      protein degradation imaged by atomic force microscopy the insoluble matrix gets
      smooth and flat indicating the removal of the attached proteins by proteases. We
      propose a model of protein coated chitin filaments for the insoluble matrix of
      nacre. Mechanical measurements by force mapping revealed a Young's modulus
      depending on the hydration state of the organic layers. The fully hydrated
      organic matrix has an elastic modulus below 1 MPa comparable to some hydrogels.

PMID- 22609100
TI  - Probing the impact of loading rate on the mechanical properties of viral
      nanoparticles.
AB  - The effects of changes in the loading rate during the forced dissociation of
      single bonds have been studied for a wide variety of interactions. Less is known
      on the loading rate dependent behaviour of more complex systems that consist of
      multiple bonds. Here we focus on viral nanoparticles, in particular the protein
      shell (capsid) that protects the viral genome. As model systems we use the well
      studied capsids of the plant virus Cowpea Chlorotic Mottle Virus (CCMV) and of
      the bacteriophages phi29 and HK97. By applying an atomic force microscopy (AFM)
      nanoindentation approach we study the loading rate dependency of their mechanical
      properties. Our AFM results show very diverse behaviour for the different
      systems. In particular, we find that not only the breaking force, but also the
      spring constant of some capsids depend on the loading rate. We describe and
      compare the measured data with simulation results from the literature. The
      unexpected complex loading rate dependencies that we report present a challenge
      for the current theoretical considerations aimed at understanding the molecular
      level interactions of highly ordered protein assemblies.

PMID- 22609102
TI  - Acute exposure of L6 myotubes to cis-9, trans-11 and trans-10, cis-12 conjugated
      linoleic acid isomers stimulates glucose uptake by modulating Ca2+/calmodulin
      dependent protein kinase II.
AB  - Conjugated linoleic acid (CLA), a dietary fat, has been considered beneficial in
      metabolic syndrome. Despite several findings indicating that CLA improves glucose
      clearance, little information is available regarding the cellular dynamics of CLA
      on skeletal muscle. We sought to investigate the role of Ca(2+)/calmodulin
      dependent protein kinase II (CaMKII) in cis-9, trans-11(c9,t11) and trans-10, cis
      12 (t10,c12) CLA isomer-mediated glucose transport by L6 myotubes. t10,c12-CLA
      stimulated both intracellular Ca(2+) release (Ca(i)(2+)) and CaMKII
      phosphorylation, whereas c9,t11-CLA showed only modest effects on both.
      Sequestering Ca(i)(2+) with BAPTA/AM abrogated the effect of both CLA isomers on
      Akt substrate-160 kDa (AS160) phosphorylation and glucose uptake by myotubes.
      Exposing myotubes to KN-93 or autocamtide 2-related inhibitory peptide to block
      CaMKII activity prevented both CLA isomers from inducing AS160 phosphorylation
      and glucose transport. Likewise, genetic knockdown of CaMKII in myotubes using
      siRNA completely abolished CLA isomer-mediated glucose uptake. These results
      indicate that CLA isomers require Ca(i)(2+)-CaMKII to mediate glucose uptake.
      Evidence that CaMKII blockers inhibit t10,c12-CLA-mediated AMP-activated protein
      kinase (AMPK) activation indicated that CaMKII acts upstream of AMPK in response
      to t10,c12-CLA. Lastly, CLA isomers stimulated the formation of reactive oxygen
      species but had no effect on stress-activated protein kinase/c-jun NH(2)-terminal
      kinase. These data establish that t10,c12-CLA acts via Ca(i)(2+)-CaMKII-AMPK
      AS160 to stimulate skeletal muscle glucose transport, whereas the mechanism of
      c9,t11-CLA remains unclear. Given that impairments in muscle glucose utilisation
      are apparent in metabolic syndrome, delineating the molecular mechanisms by which
      CLA isomers mediate muscle glucose uptake may identify new approaches to manage
      this condition.

PMID- 22609101
TI  - Mitochondria: signaling with phosphatidic acid.
AB  - Mitochondria, once viewed as functioning relatively autonomously in the cell,
      have increasingly been recognized to be involved in numerous signaling networks
      that impact on a wide range of cell biological processes. In addition to the many
      types of proteins that mediate these pathways, the importance of signaling
      functions regulated via lipids and lipid second messengers generated on the
      mitochondrial surface is also becoming well appreciated. We focus here on
      phosphatidic acid, a lipid second messenger produced via several different
      pathways that can in turn stimulate the formation of multiple other bioactive
      lipids. Taken together, fascinating roles for phosphatidic acid and the connected
      lipids in mitochondrial function and interaction with other organelles are being
      uncovered. These pathways present new opportunities for the development of
      therapeutic approaches relevant to reproduction, metabolism, and
      neurodegenerative disease.

PMID- 22609103
TI  - Spreading of West Nile virus infection in Croatia.
AB  - West Nile virus (WNV) is an emerging zoonotic pathogen with rapid global
      expansion. The virus circulation is confirmed in many countries of Mediterranean
      Basin and Southern and Central Europe. In our study detection of specific WNV
      antibodies was performed in horses and cattle sera samples collected from October
      2010 to April 2011. Serum samples were randomly taken from different parts of
      Croatia and tested by IgG and IgM ELISA. Positive serological results were
      confirmed by virus neutralization assay (VN-assay) and plaque reduction
      neutralization test (PRNT). Results showed that WNV antibodies were present in 72
      out of 2098 horse sera (3.43%) and 3 of 2695 cattle sera (0.11%). The highest
      seroprevalence was found in Eastern Croatia in counties next to Hungarian,
      Serbian and Bosnia and Herzegovinian state borders. In Adriatic part of Croatia
      positive animals were found only in the westernmost county, near Slovenian and
      Italian borders. Geographic distribution and number of positive horses indicated
      that WNV is highly present in Croatia and spreading from East to West. However,
      positive horses in westernmost part of country indicate possible second origin of
      spreading. Location of serological positive cattle supports the hypothesis that
      seropositive cattle could be indicators of high WNV activity in the respective
      geographic regions.

PMID- 22609104
TI  - Comments on the "PI and fuzzy logic controllers for shunt active power filter--a
      report" [ISA Trans. 51 (2012) 163-169].

PMID- 22609105
TI  - The sterile immune response during hepatic ischemia/reperfusion.
AB  - Hepatic ischemia and reperfusion elicits an immune response that lacks a
      microbial constituent yet poses a potentially lethal threat to the host. In this
      sterile setting, the immune system is alarmed by endogenous danger signals that
      are release by stressed and dying liver cells. The detection of these immunogenic
      messengers by sentinel leukocyte populations constitutes the proximal trigger for
      a self-perpetuating cycle of inflammation, in which consecutive waves of
      cytokines and chemokines orchestrate the influx of various leukocyte subsets that
      ultimately confer tissue destruction. This review focuses on the temporal
      organization of sterile hepatic inflammation, using surgery-induced trauma as a
      template disease state.

PMID- 22609106
TI  - Workshop on Animal free Detection of Pertussis Toxin in Vaccines--Alternatives to
      the Histamine Sensitisation Test.
AB  - The Paul-Ehrlich-Institut (PEI), the Nederlands Vaccin Instituut (NVI) and the
      European Directorate for the Quality of Medicines & HealthCare (EDQM) organised
      the international scientific workshop "Animal free Detection of Pertussis Toxin
      in Vaccines--Alternatives to the Histamine Sensitisation Test" at the PEI in
      Langen (Germany) on 09-10 June 2011. Twenty-seven experts (regulators,
      representatives from national control laboratories, vaccine manufacturers and
      academia) from 7 countries participated in this workshop. The meeting was
      triggered by the lack of satisfaction with the current safety testing for
      acellular pertussis vaccines, the "Histamine Sensitisation Test" (HIST) in mice,
      and the growing attention for the alternatives under development. The workshop
      objectives were: a) to review the current status of available alternative
      methods, b) to discuss the sensitivity that an alternative test needs, c) to plan
      experiments that allow for comparison of the alternative tests. The results of
      the workshop are summarised in this meeting report.

PMID- 22609107
TI  - Improved risk assessment of endometrial cancer by combined analysis of MSI, PI3K
      AKT, Wnt/beta-catenin and P53 pathway activation.
AB  - OBJECTIVE: To investigate if analysis of genetic alterations in the main pathways
      involved in endometrioid type carcinogenesis (PI3K-AKT, Wnt/beta-catenin, P53
      activation and MSI) improves the current risk assessment based on
      clinicopathological factors. METHODS: Formalin fixed paraffin embedded (FFPE)
      primary tumor samples of 65 patients with FIGO-stage I endometrioid type
      endometrial cancer (EEC) were selected from the randomized PORTEC-2 trial. Tumors
      were stained by immunohistochemistry for P53, PTEN and beta-catenin. Tumor DNA
      was isolated for sequence analysis of TP53 (exons 4 to 8), hotspot mutation
      analysis of KRAS (exon 1) and PI3K (exon 9 and 20) and microsatellite-instability
      (MSI) analysis including MLH1 promotor-methylation status. Univariate and
      multivariate analyses for disease-free survival (DFS) using Cox regression models
      were performed. RESULTS: P53 status (HR 6.7, 95%CI 1.75-26.0, p=0.006) and MSI
      were the strongest single genetic prognostic factors for decreased DFS, while
      high PI3K-AKT pathway activation showed a trend and beta-catenin was not
      prognostic. The combination of multiple activated pathways was the most powerful
      prognostic factor for decreased DFS (HR 5.0; 95%CI 1.59-15.6 p=0.006). Multiple
      pathway activation, found in 8% of patients, was strongly associated with
      aggressive clinical course. In contrast, 40% of patients had no alterations in
      the investigated pathways and had a very low risk of disease progression.
      CONCLUSIONS: Activation of multiple oncogenic pathways in EEC was the most
      powerful prognostic factor for decreased DFS, resulting in an individual risk
      assessment superior to the current approach based on clinicopathological factors.

PMID- 22609108
TI  - Phase II trial of paclitaxel and nedaplatin in patients with advanced/recurrent
      uterine cervical cancer: a Kansai Clinical Oncology Group study.
AB  - OBJECTIVE: A multicenter phase II trial was conducted to evaluate the activity
      and toxicity of paclitaxel and nedaplatin (cis-diammineglycolatoplatonum) in
      patients with advanced/recurrent uterine cervical cancer. METHODS: Patients were
      required to have measurable disease. Histologic confirmation of the primary
      diagnosis as uterine cervical cancer was mandatory. The treatment consisted of
      paclitaxel 175 mg/m(2) over 3 hours and nedaplatin 80 mg/m(2) intravenously over
      1 hour on day 1 every 28 days until progressive disease or adverse effects
      prohibited further therapy. RESULTS: Fifty patients were enrolled into the study
      protocol from October 2007 to February 2010. 45 patients(90%) were eligible for
      assessment of response (RECIST version 1.0) to treatment; 31 patients (62%)
      received prior radiotherapy and 23 patients (46%) received prior chemotherapy.
      The overall response rate was 44.4% (11 complete responses and 8 partial
      responses) with 22.2% of patients having stable disease. Grades 3 or 4 adverse
      events (NCI-CTCAE ver 3) included neutropenia (n=16, 32.7%), febrile neutropenia
      (n=1, 2.0%), anemia (n=9, 18.4%), but there was no significant thrombocytopenia.
      Non-hematologic toxicity was generally not serious and without a dominant
      pattern. The median progression-free survival was 7.5 months (95% C.I., 5.7, 9.4)
      and overall survival was 15.7 months (95% C.I., 9.4, 21.9). CONCLUSIONS:
      Paclitaxel 175 mg/m(2) and nedaplatin 80 mg/m(2) intravenously on day 1 every 28
      days in patients with advanced/recurrence uterine cervical cancer demonstrated
      easy administration, favorable antitumor activity, and the toxicity profile of
      this regimen would be decreased compared with cisplatin-containing combinations.
      Evaluation of this regimen in phase III trials is warranted.

PMID- 22609110
TI  - Magnetic resonance imaging performs better than endocervical curettage for
      preoperative prediction of cervical stromal invasion in endometrial carcinomas.
AB  - OBJECTIVE: Preoperative identification of cervical stromal invasion in
      endometrial carcinoma is important to select patients for primary radical
      hysterectomy. The objective of this prospective implementation study was to
      assess if introduction of magnetic resonance imaging (MRI) in addition to the
      standardly applied endocervical curettage (ECC), improved the preoperative
      prediction of cervical stromal invasion. METHODS: Over a six-year period, a total
      of 338 patients were surgically staged after preoperative assessment of the
      uterine cervix by ECC (years 1 through 3), and a combination of MRI and ECC
      (years 4 through 6). Suggested presence of cervical stromal invasion based on ECC
      (n=321) and MRI (n=146) were compared for diagnostic performance applying
      surgical FIGO stage 2009 as reference standard. RESULTS: For assessment of
      cervical stromal invasion sensitivity (specificity) [accuracy] values were 65%
      (79%) [77%] for ECC and 59% (91%) [84%] for MRI. Among patients diagnosed with
      both preoperative tests (n=129), MRI yielded significantly higher specificity
      (p=0.001) and accuracy (p=0.005) than ECC. MRI independently predicted cervical
      stromal invasion with an odds ratio (OR) of 11.2 (p<0.001) compared to OR of 2.7
      (p=0.07) for ECC. CONCLUSIONS: The diagnostic performance of MRI compares
      favorably to that of ECC for preoperative assessment of cervical stromal invasion
      in endometrial carcinoma. Thus, the findings in this prospective implementation
      study support the value of preoperative MRI for assessment of cervical stromal
      invasion before radical hysterectomy.

PMID- 22609111
TI  - Unraveling the two entities of endometrioid ovarian cancer: a single center
      clinical experience.
AB  - OBJECTIVE: Due to the increasing prevalence of the benign condition, ovarian
      carcinoma arising from endometriosis is emerging as a relevant clinical entity
      with an unclear biological signature. We have investigated clinical and
      histologic features of endometriosis-associated endometrioid ovarian cancer using
      an institutional retrospective database. METHODS: Patients diagnosed with
      endometrioid ovarian cancer at our institution were divided into two groups
      according to the fulfillment or not of Sampson's and Scott's criteria for the
      detection of endometriosis-associated ovarian cancer. Clinical and histological
      data were reported and compared. Survival analysis was obtained using the log
      rank test in an unadjusted Kaplan-Meier method. Multivariate analysis was
      performed using the Cox proportional hazards regression model to establish
      independent factors associated with endometriosis-associated endometrioid ovarian
      cancer and to identify predictors of survival. The degree of concordance was
      evaluated by Cohen's Kappa measures. RESULTS: Patients with endometriosis
      associated endometrioid ovarian cancer were significantly younger, had a lower
      disease stage (62% vs 23%; p=0.003), a less prevalent high grade tumor (38% vs
      82%; p=0.002) and a higher prevalence of squamous and mucinous metaplasia. The
      rate of endometrial cancer diagnosis was significantly higher in women with
      endometriosis-associated endometrioid ovarian cancer (33%) than in other patients
      (11%) (p=0.04) with a 92% concordance between ovarian and endometrial histologic
      tumor grade. A significant difference in survival rate could not be demonstrated
      between patients with or without endometriosis. CONCLUSIONS: The analysis of a
      retrospective endometrioid ovarian cancer database may allow to suggest a 40
      molecular, morphological and clinical parallelism between endometrial and
      endometrioid ovarian cancers.

PMID- 22609112
TI  - Rhabdomyosarcoma of the cervix in adult women and younger patients.
AB  - OBJECTIVES: Cervical rhabdomyosarcoma is extremely rare, and there is a paucity
      of literature on the subject. The purpose of this study was to describe the
      clinical and pathologic features of cervical rhabdomyosarcoma. METHODS: We
      retrospectively reviewed all patients with cervical rhabdomyosarcoma who
      presented to our institution from 1980 to 2010. We reviewed pathologic,
      demographic, and clinical information. RESULTS: During the study period, 11
      females presented with cervical rhabdomyosarcoma. The median age at presentation
      was 18.4 years, and 6 patients were <19 years old at diagnosis. Vaginal bleeding
      was the most common presenting symptom, and a vaginal mass was often a co
      presenting symptom. Eight patients (73%) presented with stage IB disease, and 8
      (73%) presented with the embryonal (botryoid) histologic subtype. Nine patients
      (82%) received multimodal therapy consisting of surgery with chemotherapy,
      radiation therapy, or both. All patients were without evidence of disease after
      completion of primary therapy, but 3 patients experienced local recurrence. At a
      median follow-up of 23 months, 6 patients (55%) were without evidence of disease,
      1 (9%) was alive with disease, 1 (9%) had died of disease, and 3 (27%) had died
      of other causes. Three patients (27%) had other primary malignancies in addition
      to rhabdomyosarcoma-1 had a Sertoli-Leydig tumor, 1 had a Sertoli-Leydig tumor
      and a pinealoblastoma, and 1 had thyroid cancer and a parotid adenocarcinoma.
      CONCLUSIONS: With multimodal therapy, cervical rhabdomyosarcoma appears to be
      associated with a good prognosis. Favorable prognostic factors such as early
      stage at diagnosis and a favorable histologic subtype may contribute to the
      excellent observed survival.

PMID- 22609113
TI  - Novel metal-based anticancer drugs: a new challenge in drug delivery.
AB  - Since the serependitous discovery of the cisplatin antiproliferative activity,
      many efforts have focused on the design of potent metal-based drugs for oncology
      therapies. A large number of these complexes have been evaluated in vitro and in
      vivo and some have reached clinical trials. However, while metallodrug chemistry
      has developed to an advanced level, these emerging therapeutics have encountered
      new hurdles including poor water solubility and pharmacological deficiencies.
      Today, solutions to overcome these issues do not lie in synthesizing new
      anticancer drugs but in finding suitable drug delivery strategies. Over the past
      decades, various delivery systems have been developed including prodrug, ligand
      design and nanocarriers aimed at enhancing the performance profile of these novel
      metallodrugs.

PMID- 22609114
TI  - Simultaneous attenuation and scatter corrections from the projections in small
      animal PET imaging.
AB  - Attenuation and scatter corrections are important in quantitative positron
      emission tomography (PET) imaging even in small animals such as mice and rats. In
      this work we describe a simple and efficient model to correct for both scatter
      and attenuation in a single operation. The model aims to solve the equation
      M=(A+F) P for the primaries P, corrected for attenuation and scatter, based on
      the measured coincidences M, the matrix of compensation for attenuation A and on
      the scatter fractions F issued from all emitting sources and contributing to M.
      The scatter functions are analytically calculated using Klein-Nishina formula,
      the scanner geometry and the detection efficiencies. This method was applied in
      measured data of line sources and hot spots phantoms as well as in rat heart and
      tumors and compared to Monte Carlo based simulations and to the single scatter
      simulation model developed by Watson et al. The corrected data showed a
      quantitative contrast and signal to noise ratio enhancement with respect to the
      uncorrected data. In terms of results, our method is comparable to that of Watson
      et al. The Monte Carlo simulations, where the primaries and the scattered events
      were separately registered, confirmed the accuracy of the new approach.

PMID- 22609115
TI  - Overexpression of IFITM1 has clinicopathologic effects on gastric cancer and is
      regulated by an epigenetic mechanism.
AB  - In an effort to identify novel genes related to the prognosis of gastric cancer,
      we performed gene expression profiling and found overexpressed levels of human
      interferon-induced transmembrane protein 1 (IFITM1). We validated the gastric
      cancer-specific up-regulation of IFITM1 and its association with cancer
      progression. We also studied its epigenetic regulation and tumorigenesis-related
      functions. Expression of IFITM1 was evaluated in various human gastric cancer
      cells and in 35 patient tumor tissues by quantitative RT-PCR and Western blot
      analyses. The results showed highly up-regulated IFITM1 in cancer cell lines and
      tissues. Furthermore, IHC studies were performed on 151 patient tissues, and a
      significant correlation was revealed between higher IFITM1 expression and
      Lauren's intestinal type (P = 0.007) and differentiated adenocarcinoma (P =
      0.025). Quantitative studies of DNA methylation for 27 CpG sites in the
      regulatory region showed hypermethylation in cells expressing low levels of
      IFITM1. Methylation-dependent IFITM1 expression was confirmed further by in vitro
      demethylation using 5-aza-2'-deoxycytidine and luciferase assays. The functional
      analysis of IFITM1 by silencing of its expression with small-interfering RNA
      showed decreased migration and invasiveness of cancer cells, whereas its
      overexpression exhibited the opposite results. In this study, we demonstrated
      gastric cancer-specific overexpression of IFITM1 regulated by promoter
      methylation and the role of IFITM1 in cancer prognosis.

PMID- 22609116
TI  - Quantitative proteomics reveals that miR-155 regulates the PI3K-AKT pathway in
      diffuse large B-cell lymphoma.
AB  - The aberrant expression of microRNA-155 (miR-155), which has emerged as having a
      significant impact on the biological characteristics of lymphocytes, plays
      important roles in B-cell malignancies, such as diffuse large B-cell lymphoma
      (DLBCL). DLBCL is the most common non-Hodgkin's lymphoma in the adult population,
      accounting for approximately 40% of newly diagnosed non-Hodgkin's lymphoma cases
      globally. To determine the specific function of miR-155, a quantitative
      proteomics approach was applied to examine the inhibitory effects of miR-155 on
      protein synthesis in DLBCL cells. PIK3R1 (p85alpha), a negative regulator of the
      phosphatidylinositol 3-kinase (PI3K)-AKT pathway, was identified as a direct
      target of miR-155. A luciferase reporter was repressed through the direct
      interaction of miR-155 and the p85alpha 3'-untranslated region, and
      overexpression of miR-155 down-regulated both the transcription and translation
      of p85alpha. The PI3K-AKT signaling pathway was highly activated by the sustained
      overexpression of miR-155 in DHL16 cells, whereas knockdown of miR-155 in OCI-Ly3
      cells diminished AKT activity. Taken together, our results reveal a novel target
      involved in miR-155 biological characteristics and provide a molecular link
      between the overexpression of miR-155 and the activation of PI3K-AKT in DLBCL.

PMID- 22609117
TI  - Effectiveness of a multifactorial intervention program to reduce falls incidence
      among community-living older adults: a randomized controlled trial.
AB  - OBJECTIVE: To determine the effectiveness of a multifactorial intervention
      program to prevent falls among older adults as compared with a brief
      intervention. DESIGN: Randomized controlled trial. SETTING: Eleven health centers
      located in Cordoba, Spain. PARTICIPANTS: People over 70 years old (N=404), who
      are residents in the community. INTERVENTIONS: The centers were randomized to
      either 1 of the 2 groups: intervention group (IG), of a multifactorial nature
      (individual advice, information leaflet, physical exercise workshop, and home
      visits), or control group (CG) (brief individual advice and information leaflet).
      MAIN OUTCOME MEASURES: Fall rates and time until the fall; estimates of the
      relative and absolute risk of falls; and survival analysis and Cox regression.
      RESULTS: Of the patients recruited, 133 were in the IG and 271 were in the CG.
      Around 33% in the IG and 30.25% in the CG had had a fall in the previous year
      (P=.56). After 12 months, the fall incidence rate was 17.29% in the IG and 23.61%
      in the CG (relative risk=0.73; 95% confidence interval [CI], 0.48-1.12; P=.146).
      Around 60% of the IG patients said they had increased the time spent on physical
      activity. In the IG, the incidence of falls at home was 27.5% compared with 49.3%
      in the CG (P=.04). Being a woman (odds ratio [OR]=1.62; 95% CI, 1.03-2.54),
      having a history of falls (OR=1.15; 95% CI, 1.05-1.26), suffering acute health
      problems (OR=2.19; 95% CI, 1.09-4.40), and doing moderate exercise (OR=1.91; 95%
      CI, 1.08-3.38) were found as factors associated with a higher risk of falls.
      CONCLUSIONS: Although the reduction of falls in the IG was nearly halved, and
      after the intervention there was a significant reduction in the number of falls
      at these patients' homes, the multifactorial intervention program is no more
      effective than the brief intervention to reduce the overall risk of falls.

PMID- 22609119
TI  - Predicting energy expenditure of manual wheelchair users with spinal cord injury
      using a multisensor-based activity monitor.
AB  - OBJECTIVE: To develop and evaluate new energy expenditure (EE) prediction models
      for manual wheelchair users (MWUs) with spinal cord injury (SCI) based on a
      commercially available multisensor-based activity monitor. DESIGN: Cross
      sectional. SETTING: Laboratory. PARTICIPANTS: Volunteer sample of MWUs with SCI
      (N=45). INTERVENTION: Subjects were asked to perform 4 activities including
      resting, wheelchair propulsion, arm-ergometer exercise, and deskwork. Criterion
      EE using a metabolic cart and raw sensor data from a multisensor activity monitor
      was collected during each of these activities. MAIN OUTCOME MEASURES: Two new EE
      prediction models including a general model and an activity-specific model were
      developed using enhanced all-possible regressions on 36 MWUs and tested on the
      remaining 9 MWUs. RESULTS: The activity-specific and general EE prediction models
      estimated the EE significantly better than the manufacturer's model. The average
      EE estimation error using the manufacturer's model and the new general and
      activity-specific models for all activities combined was -55.31%
      (overestimation), 2.30% (underestimation), and 4.85%, respectively. The average
      EE estimation error using the manufacturer's model, the new general model, and
      activity-specific models for various activities varied from -19.10% to -89.85%, 
      18.13% to 25.13%, and -4.31% to 9.93%, respectively. CONCLUSIONS: The predictors
      for the new models were based on accelerometer and demographic variables,
      indicating that movement and subject parameters were necessary in estimating the
      EE. The results indicate that the multisensor activity monitor with new
      prediction models can be used to estimate EE in MWUs with SCI during wheelchair
      related activities mentioned in this study.

PMID- 22609118
TI  - Truth be told: evidence of wheelchair users' accuracy in reporting their height
      and weight.
AB  - OBJECTIVES: To examine whether wheelchair users' self-reports of height and
      weight differed significantly from direct measurements and whether weight
      category classifications differed substantially when based on self-reported or
      measured values. DESIGN: Single group, cross-sectional analysis. Analyses
      included paired t tests, chi-square test, analysis of variance, and Bland-Altman
      agreement analyses. SETTING: A university-based exercise lab. PARTICIPANTS:
      Community-dwelling wheelchair users (N=125). INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURE: Participants' self-reported and measured height, weight, and
      body mass index. RESULTS: Paired t tests revealed that there were significant
      differences between wheelchair users' self-reported and measured values for
      height (difference of 3.1+/-7.6cm [1.2+/-3.0in]), weight (-1.7+/-6.5kg [-3.6+/
      14.2lb]), and BMI (-1.6+/-3.3). These discrepancies also led to substantial
      misclassification into weight categories, with reliance on self-reported BMI
      underestimating the weight status of 20% of the sample. CONCLUSIONS: Our findings
      suggest that similar to the general population, wheelchair users are prone to
      errors when reporting their height and weight and that these errors may exceed
      those noted in the general population.

PMID- 22609120
TI  - Primary classical hemangiopericytomas of thorax.
AB  - BACKGROUND: Hemangiopericytoma, an uncommon hypervascular tumor, occurs anywhere
      in the body with capillary vessels originating from the pericyte. These tumors
      most frequently occur in the musculature of the lower extremities and
      retroperitoneum, but are rarely seen in the thoracic cavity. The objective of
      this study is to present primary classical hemangiopericytomas of the thorax
      together with a literature review. METHODS: The postoperative pathologic records
      of 17,165 operations that were performed between January 1990 and December 2010
      in the clinic were retrospectively searched, and the files of 6 cases with the
      diagnosis of primary classical hemangiopericytoma were analyzed for clinical
      characteristics of patients, surgical procedures, histopathologic features,
      treatments after surgery, and morbidity and mortality results. RESULTS: There
      were 4 female and 2 male patients with an average age of 30.3 years (range, 15 to
      60 years). Three patients had thoracic wall lesions, 2 patients had intrathoracic
      extrapulmonary lesions, and 1 patient had mediastinal lesion. Four left and two
      right posterolateral thoracotomies were performed. Chest wall resection was
      performed in 3 patients, intrathoracic extrapulmonary mass excision in 2
      patients, and mediastinal mass excision and left lower lobectomy in 1 patient.
      Postoperative histopathologic diagnoses were primary classical
      hemangiopericytomas in 4 patients and primary classical malignant
      hemangiopericytomas in 2 patients. Four patients underwent reoperation for
      recurrence. In the follow-up period, 2 patients are still alive at 30 months and
      14 years postoperatively; 3 patients died at 7, 8, and 16 years postoperatively.
      One patient was lost to follow-up. All 3 mortalities were related to the
      recurrence or distant metastasis of the tumor. CONCLUSIONS: Although
      hemangiopericytomas are benign or malignant tumors, they generally display
      malignant behaviors. The risk of recurrence and distant metastasis occurs even
      many years after resection, suggesting that the prognosis becomes worse after
      each recurrence.

PMID- 22609121
TI  - Hemoglobin drift after cardiac surgery.
AB  - BACKGROUND: Recent literature suggests that a restrictive approach to red blood
      cell transfusions is associated with improved outcomes in cardiac surgery
      patients. Even in the absence of bleeding, intravascular fluid shifts cause
      hemoglobin levels to drift postoperatively, possibly confounding the decision to
      transfuse. The purpose of this study was to define the natural progression of
      hemoglobin levels in postoperative cardiac surgery patients. METHODS: All cardiac
      surgery patients from October 2010 through March 2011 who did not receive a
      postoperative transfusion were included. Primary stratification was by
      intraoperative transfusion status. Change in hemoglobin was evaluated relative to
      the initial postoperative hemoglobin. Maximal drift was defined as the maximum
      minus the minimum hemoglobin for a given hospitalization. Final drift was defined
      as the difference between initial and discharge hemoglobin. RESULTS: The final
      cohort included 199 patients: 71 (36%) received an intraoperative transfusion,
      whereas 128 (64%) did not. The average initial and final hemoglobin levels for
      all patients were 11.0+/-1.4 g/dL and 9.9+/-1.3 g/dL, respectively, giving a
      final drift of 1.1+/-1.4 g/dL. The maximal drift was 1.8+/-1.1 g/dL and was
      similar regardless of intraoperative transfusion status (p=0.9). Although all
      patients' hemoglobin initially dropped, 79% of patients reached a nadir and
      experienced a mean recovery of 0.7+/-0.7 g/dL by discharge. On multivariable
      analysis, increasing cardiopulmonary bypass time was significantly associated
      with total hemoglobin drift (coefficient/hour, 0.3 [0.1-0.5] g/dL; p=0.02).
      CONCLUSIONS: In this report of hemoglobin drift after cardiac surgery, although
      all postoperative patients experienced downward hemoglobin drift, 79% of patients
      exhibited hemoglobin recovery before discharge. Physicians should consider the
      eventual upward hemoglobin drift before administering red blood cell
      transfusions.

PMID- 22609122
TI  - Who performs complex noncardiac thoracic surgery in United States academic
      medical centers?
AB  - BACKGROUND: We hypothesized that general thoracic surgeons (GTS) predominantly
      perform complex noncardiac thoracic surgery in academic hospitals compared with
      cardiac surgeons (CS), general surgeons, and surgical oncologists. METHODS:
      Fiscal year 2007-2008 to 2009-2010 coding and work relative value unit data from
      the University Health System Consortium and Association of American Medical
      Colleges Faculty Practice Solutions Center database, which includes 86 academic
      institutions, was analyzed. Procedural groups for pneumonectomy, other pulmonary
      resection (including lobectomy, bilobectomy, segmentectomy, sleeve lobectomy, and
      video-assisted thoracoscopic surgery lobectomy-segmentectomy), and esophagectomy
      were evaluated. RESULTS: Of the 1,989,055.3 total work relative value units
      generated for complex noncardiac thoracic surgical procedures during the study
      period, 77.5% were generated by GTS, compared with 9.9% by CS, 8.9% by general
      surgeons, and 3.7% by surgical oncologists (p<0.001). General thoracic surgeons
      averaged 2.1 pneumonectomies, 51.1 other pulmonary resections, and 12.2
      esophagectomies per year compared with 2.1 pneumonectomies, 9.4 other pulmonary
      resections, and less than 1 esophagectomy per year for CS. General surgeons and
      surgical oncologists averaged no more than 1.6 cases per year for all categories
      (all p<0.001, except for pneumonectomy, in which GTS versus CS was not
      significantly different). To determine the use of parenchymal-sparing operations,
      we looked at the ratio of sleeve lobectomy to pneumonectomy and found higher
      usage of parenchymal-sparing techniques by GTS, relative to pneumonectomy,
      compared with all other groups (p<0.001). General thoracic surgeons averaged 16.0
      video-assisted thoracoscopic surgery lobectomies per year compared with
      approximately 1 per year for all other groups (p<0.001). General thoracic
      surgeons had a 47.1% increase in video-assisted thoracoscopic surgery lobectomies
      per year compared with 27.4% for CS. CONCLUSIONS: In academic hospitals,
      noncardiac thoracic surgery is performed mostly by GTS, supporting academic GTS
      as a distinct specialty. These results may help determine hospital referral and
      credentialing policies, and plan general and cardiothoracic surgery residency
      curriculum.

PMID- 22609123
TI  - Interpersonal factors in insomnia: a model for integrating bed partners into
      cognitive behavioral therapy for insomnia.
AB  - Sleep has largely been conceptualized as an individual phenomenon, despite the
      fact that most adults share their bed with a partner at some time in their life.
      Only recently have researchers begun to examine the dyadic nature of sleep, and
      there is growing evidence that bed partners can play a role in the onset and
      maintenance of insomnia. Additionally, emerging evidence suggests that bed
      partners can be powerful agents of social control in terms of promoting adaptive
      health and sleep-related behaviors, and shared social rhythms between partners
      can help foster an environment that is conducive to good sleep. As such, the aim
      of the present article is to review the social context of the sleep environment
      and how best to include bed partners in insomnia treatment. Based on a synthesis
      of relevant literatures, a model for integrating bed partners into cognitive
      behavior therapy for insomnia (CBT-I) is presented and directions for future
      research are discussed.

PMID- 22609124
TI  - Interventions with a sleep outcome for children with cerebral palsy or a post
      traumatic brain injury: a systematic review.
AB  - The purpose of this study was to conduct a systematic literature review on
      interventions for sleep problems in children (aged 0-12 years) with cerebral
      palsy (CP) or traumatic brain injury (TBI). The literature describes sleep
      disorders as common in both conditions. Criteria were expanded to include
      interventions for other medical conditions where sleep was measured as an
      outcome. No interventions specifically designed to improve sleeping in children
      with CP or TBI were found. A literature search was conducted of five databases
      (Ovid MEDLINE, EMBASE, PsychINFO, CINAHL, and the Cochrane Database) from January
      1 1990, to June 2011. The search terms [infant (age 0-23 months) or child,
      preschool (age 2-5 years) or child (age 6-12 years)] were used, with key terms
      related to CP and TBI. The search yielded 491 articles; 19 were relevant for CP,
      one for TBI. For CP, if the intervention improved the symptom/s targeted as
      primary outcome/s, sleep (measured as a secondary outcome) also improved. Few
      studies used objective measures of sleep, so efficacy could not be assessed. Only
      four studies were randomized controlled trials. Interventions were diverse. Where
      melatonin was used for CP patients with sleep problems/disorders, several related
      to phase or sleep maintenance disorders, improvements in sleep latency and night
      waking were consistently found, and in some subjects, improvements in total sleep
      time. No studies using melatonin studied CP patients exclusively. The one study
      where sleep was measured as a secondary outcome for TBI was of limited value. In
      conclusion, more well-designed studies are necessary to advance evidence-based
      treatments in the area of sleep problems for these chronic pediatric conditions.

PMID- 22609125
TI  - Pulmonary delivery of dry powders to rats: tolerability limits of an intra
      tracheal administration model.
AB  - The inhaled route is increasingly developed to deliver locally acting or systemic
      therapies, and rodent models are used to assess tolerance before clinical
      studies. Endotracheal intubation of rats with a probe which generates powder
      aerosols enables controlled administration of drug directly into the respiratory
      tract. However, preliminary observations of intratracheal powder administration
      procedures have raised concerns with regard to pulmonary safety. The aim of the
      present work was to evaluate the safety of intra-tracheal administration of dry
      powder in a rat model. Sixty animals were administered various volumes of air
      alone, lactose or magnesium stearate through a Microsprayer((r)) (Pencentury,
      USA). The mass of powder actually delivered to each animal was calculated. Rats
      were sacrificed immediately after administration, and the lungs, trachea and
      larynx were removed and examined for gross pathology. The mass of powder
      delivered varied, the full dose being rarely delivered. About one third of the
      administration procedures resulted in respiratory failure, and macroscopic
      pulmonary lesions were observed in about 55% of animals. Lung damages were
      observed with air alone, lactose and magnesium stearate. In conclusion, artifacts
      observed with this technique may limit the relevance of the model. These
      observations are particularly important in the context of regulatory toxicity
      studies.

PMID- 22609126
TI  - Direct measurement of the time-dependent mechanical response of HPMC and PEO
      compacts during swelling.
AB  - Mechanical indentation is used to measure the time dependent mechanical
      properties of three model compact formulations during swelling in aqueous media.
      The formulations are based on polyethylene oxide (PEO), hydroxypropyl
      methylcellulose (HPMC) and a PEO/HPMC blend. The technique is sensitive to
      changes in compact thickness and mechanical response and is used to characterize
      changes in the mechanical properties of the model compacts during the swelling
      process. The gel thickness and the effective elastic modulus of the gel layer are
      obtained from the load/displacement relationship during initial indentation. The
      HPMC and hybrid compacts showed significantly more swelling (110%) than the PEO
      compact (67%). Viscoelastic properties of the gel layer are determined throughout
      the swelling process by an oscillatory indentation method. Results show the
      complex modulus of all three compacts decreasing by approximately an order of
      magnitude over the course of swelling for 6h. The measurement techniques
      presented here can easily be extended to more complex systems.

PMID- 22609127
TI  - Polysorbate 80 coated poly (E-caprolactone)-poly (ethylene glycol)-poly (E
      caprolactone) micelles for paclitaxel delivery.
AB  - In this article, polysorbate 80 coated poly (E-caprolactone)-poly (ethylene
      glycol)-poly (E-caprolactone) (PCEC) micelles were successfully prepared for
      paclitaxel (PTX) delivery. The particle size distribution, morphology, drug
      loading, encapsulation efficiency and sustained release profile of the micelles
      were studied in detail. The safety of the micelle formulation was evaluated by
      MTT assay on HEK293 cells. And the encapsulated PTX in the micelles remained
      potent antitumor effect on C6 glioma cells. The pharmacokinetic study showed that
      the PCEC micelles coated with polysorbate 80 altered the biodistribution pattern
      and increased PTX concentration in the brain significantly compared to the
      uncoated micelles and the free drug after intravenous injection. The results
      indicated that polysorbate 80 coated PCEC micelles might be a candidate for PTX
      delivery for brain tumor chemotherapy.

PMID- 22609128
TI  - A preliminary investigation into a simple method for the determination of the
      mean ionisation energy of gas mixtures used in the NPL primary gas counting
      system.
AB  - The activity concentration of gaseous beta-emitting radionuclides such as (3)H,
      (85)Kr and, more recently, (11)C, is measured at NPL using a set of length
      compensated proportional counters. The active gas is mixed with argon-methane (P
      10) and passed to the counters. Adding gases to P-10 changes the mean ionisation
      energy, W, of the gas mixture. Estimation of the counting losses using the Monte
      Carlo model requires a knowledge of W. Unfortunately, only a limited amount of
      published data is available. This paper describes the initial experimental
      studies performed to enable the extension of the MC model based loss correction
      method to gases other than carbon dioxide in P-10. Preliminary measurements have
      been made to determine the W value for a gas mixture containing (85)Kr in
      nitrogen and P-10. The DC current through the counters is measured; the counters
      are also operated in the normal way with pulse amplifiers, discriminators and
      scalers. The value of W is derived from a knowledge of activity, counter current
      and mean beta energy.

PMID- 22609129
TI  - High-resolution melting assay (HRMA) is a simple and sensitive stool-based DNA
      Test for the detection of mutations in colorectal neoplasms.
AB  - BACKGROUND: Stool-based DNA testing for colorectal cancer is becoming a favored
      alternative to existing DNA screening tests. However, current methods of analysis
      often become more complicated and costly with increased sensitivity. The high
      resolution melting assay (HRMA) is a simple and rapid mutation scanning method
      with low cost and superb accuracy. In this study, we verified the accuracy of
      HRMA for screening KRAS/TP53 mutations in stool-isolated DNA from patients with
      colorectal cancer. MATERIALS AND METHODS: Comparing to direct DNA sequencing, the
      accuracy of HRMA was verified by detecting KRAS/TP53 mutations in 2 independent
      stages. In study stage I, both tissue and stool samples from colorectal neoplasm
      patients were analyzed. In study stage II, stool samples from patients with
      colorectal neoplasms, and normal controls in clinical screening settings were
      examined. RESULTS: In study stage I, the HRMA identified 14 of 17 target
      mutations (82.4%) in stools from cancer patients, and 4 of 5 (80.0%) target
      mutations in stools from advanced adenoma patients. The mutation detection rate
      in fecal samples (45.0%; 18/40) and referred tissue samples (55.0%; 22/40) was
      highly consistent (kappa = 0.79). The HRMA detected 1% mutant DNA in a background
      of wild type DNA. In study stage II, the HRMA assay detected 58.8% (20/34)
      mutations in tumor samples, 41.5% (17/41) in advanced adenomas samples, and 3.33%
      (2/60) in age-matched normal control samples. The results from HRMA and DNA
      sequencing revealed 100% sensitivity and specificity in both tissue and stool
      samples. CONCLUSION: HRMA is a simple, reliable, and sensitive method for
      detecting DNA mutations in the stool samples from patients with colorectal
      neoplasms.

PMID- 22609130
TI  - Cardiographic conundrum: adding insult to injury.

PMID- 22609131
TI  - From excess adiposity to insulin resistance: the role of free fatty acids.
AB  - With a positive caloric balance, adipocytes undergo excessive hypertrophy, which
      causes adipocyte dysfunction, as well as adipose tissue endocrine and immune
      responses. A preferential site of fat accumulation is the abdominal-perivisceral
      region, due to peculiar factors of the adipose tissue in such sites, namely an
      excess of glucocorticoid activity, which promotes the accumulation of fat; and
      the greater metabolic activity and sensitivity to lipolysis, due to increased
      number and activity of beta3-adrenoceptors and, partly, to reduced activity of
      alpha2-adrenoceptors. As a consequence, more free fatty acids (FFA) are released
      into the portal system. Hypertrophic adipocytes begin to secrete low levels of
      TNF-alpha, which stimulate preadipocytes and endothelial cells to produce MCP-1,
      in turn responsible for attracting macrophages to the adipose tissue, thus
      developing a state of chronic low-grade inflammation which is causally linked to
      insulin resistance. Excess of circulating FFA, TNF-alpha and other factors
      induces insulin resistance. FFA cause insulin resistance by inhibiting insulin
      signaling through the activation of serin-kinases, i.e. protein kinase C-Theta,
      and the kinases JNK and IKK, which promote a mechanism of serine phosphorylation
      of Insulin Receptor Substrates (IRS), leading to interruption of the downstream
      insulin receptor (IR) signaling. TNF-alpha, secreted by hypertrophic adipocytes
      and adipose tissue macrophages, also inhibits IR signaling by a double mechanism
      of serine-phosphorylation and tyrosine-dephosphorylation of IRS-1, causing
      inactivation and degradation of IRS-1 and a consequent stop of IR signaling. Such
      mechanisms explain the transition from excess adiposity to insulin resistance,
      key to the further development of type 2 diabetes.

PMID- 22609132
TI  - NO and EDHF pathways in pulmonary arteries and veins are impaired in COPD
      patients.
AB  - We investigated endothelial function of both pulmonary arteries and veins in
      patients with chronic obstructive pulmonary disease (COPD) of varying severity in
      regard to the role of nitric oxide (NO) and endothelium-derived hyperpolarizing
      factor (EDHF). Lung tissues were obtained from patients undergoing lobectomy or
      pneumonectomy. Patients were grouped to control, moderate COPD, and severe COPD
      according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD)
      guidelines. Pulmonary arteries and veins were studied for endothelium-dependent
      relaxations. NO concentration was measured by electrochemical method. Protein
      expressions of eNOS and phosphorylated eNOS were determined by Western-blot.
      Endothelium-dependent relaxation was more significant in pulmonary arteries than
      in veins. The vasorelaxation was decreased in patients of moderate COPD and
      further decreased in severe COPD. The severity of endothelial dysfunction in both
      pulmonary arteries and veins correlated with the degree of airflow obstruction.
      COPD patients exhibited reduced endothelial NO production, decreased eNOS protein
      expression and decreased eNOS phosphorylation. The EDHF component was abolished
      in the pulmonary vasculature of patients with severe COPD. NO and EDHF pathways
      are both involved in the regulation of vascular tone in human pulmonary arteries
      and veins. Both pathways are impaired in COPD patients and the severity of the
      impairment increases with the progress of the disease. Downregulation of eNOS
      expression and inhibition of eNOS activation underlie the reduction of NO in COPD
      patients.

PMID- 22609133
TI  - The emerging challenge in diabetes: the "metabolic memory".
AB  - Large randomized studies have established that early intensive glycemic control
      reduces the risk of diabetic complications, both micro and macrovascular.
      However, epidemiological and prospective data support a long-term influence of
      early metabolic control on clinical outcomes. This phenomenon has recently been
      defined as "metabolic memory." Potential mechanisms for propagating this "memory"
      may be the production of reactive species unrelated to the presence of
      hyperglycemia, depending on the previous production of AGEs which can maintain
      RAGE over-expression, on the level of glycation of mitochondrial proteins and on
      the amount of mtDNA produced, all conditions able to induce an altered gene
      expression which may be persistent even when glycemia is normalized. Clinically,
      the emergence of this "metabolic memory" suggests the need for a very early
      aggressive treatment aiming to "normalize" the metabolic control and the addition
      of agents which reduce cellular reactive species and glycation in addition to
      normalizing glucose levels in diabetic patients in order to minimize long-term
      diabetic complications.

PMID- 22609134
TI  - The usefulness of combining traditional sperm assessments with in vitro
      heterospermic insemination to identify bulls of low fertility as estimated in
      vivo.
AB  - To date, no single in vitro assessment can estimate bull fertility. This research
      was aimed at evaluating the ability of a series of laboratory assessments to
      assign 50 Holstein Friesian bulls grouped as low (ER-NRR<-1.5), medium (-0.5<ER
      NRR<+0.5) and high (ER-NRR>=+1.5) fertility based on estimated relative non
      return rates (ER-NRR), to the two categories of low and medium-high fertility.
      Heterospermic insemination with a Piedmontese reference bull was employed to
      define an index of competitive binding ability (CBI) to the zona pellucida using
      fluorochrome-labeled sperm, and a competitive fertility index (CFI) using embryo
      paternal assignment by single nucleotide polymorphism (SNP). Furthermore, kinetic
      parameters, membrane integrity and sperm DNA/chromatin integrity (% DFI) were
      assayed. Low fertility bulls had lesser (P<0.05) values for total motility and
      membrane integrity, and a greater value of % DFI as compared to medium and high
      fertility groups. A modest (P<0.001) correlation was reported among ER-NRR and
      total motility (r=0.30), progressive motility (r=0.26), membrane integrity
      (r=0.43) and % DFI (r=-0.26). While % DFI alone allowed the identification of 70%
      lowly fertile bulls, combining membrane integrity, average path velocity and CBI
      allowed for identification of 78% of the lowly fertile sires. Paternal assignment
      by SNPs resulted in 96% of successful assignments and could provide an
      alternative support to microsatellites for in vivo studies based on heterospermic
      fertilization for estimating fertility.

PMID- 22609135
TI  - Pharmacovigilance of oral bisphosphonates: adverse effects manifesting in the
      soft tissue of the oral cavity.
AB  - PURPOSE: It is well known that oral bisphosphonates can induce necrosis of the
      osseous structures of the jaws. However, there seems to be a limited awareness
      that oral bisphosphonates can also induce adverse effects in the soft tissues of
      the oral cavity, as indicated by the paucity of reported cases in the literature.
      Because oral bisphosphonates are widely used drugs for several skeletal
      conditions, it is reasonable to assume that mucosal adverse effects are more
      common than the small number of published cases indicates. The purpose of this
      study was to investigate whether this adverse effect of bisphosphonates is
      represented as reports from health practitioners in an adverse drug reaction
      database, as well as to gain knowledge about which substances are being
      associated with adverse drug reactions affecting the oral mucosa. MATERIALS AND
      METHODS: The database of the Medical Products Agency-Sweden was searched for
      adverse effects from oral bisphosphonates manifesting in the oral and
      maxillofacial region. Reports of reactions limited to the soft tissues of the
      oral cavity were selected and further analyzed. Only those reports showing
      recovery or improvement after the cessation of bisphosphonate use were included
      in the study. RESULTS: A total of 83 cases of adverse reactions to oral
      bisphosphonates were retrieved from the search. Of these, 12 were included in the
      study. They were associated with the use of alendronate, etidronate and
      risedronate, in descending order. Sixteen percent of the reports comprising the
      oral and maxillofacial region were limited to the oral mucosa and reported
      recovery or improvement after discontinuation of the drug. CONCLUSIONS: Adverse
      effects of oral bisphosphonates with manifestations in the soft tissue of the
      oral cavity seem to be more common than the small number of published cases
      indicates. However, considering that oral bisphosphonates are widely used drugs,
      the incidence is still low. These adverse drug reactions are not limited to
      alendronate and may also be induced by etidronate and risedronate. Still, a
      significant proportion of the cases are associated with alendronate. Regardless
      of the substance used, discontinuing the drug is an effective treatment for the
      mucosal lesions.

PMID- 22609136
TI  - [Renal vein infarction, a complication of paroxysmal nocturnal hemoglobinuria].
AB  - Paroxysmal nocturnal hemoglobinuria (Marchiafava-Micheli disease) is a rare
      acquired clonal disorder of the hematopoietic cell, to a somatic mutation in the
      phosphatidylinositol glycan (PIG-A). The most frequent clinical manifestations
      are hemolytic crisis and venous thrombosis of the mesenteric, hepatic, portal or
      cerebral territories. We report a case of paroxysmal nocturnal hemoglobinuria
      with renal vein thrombosis, a rare complication of this disease.

PMID- 22609137
TI  - Self harm in adult inpatient psychiatric care: a national study of incident
      reports in the UK.
AB  - BACKGROUND: We know little about the nature of self harming behaviour within
      inpatient psychiatric services. The few studies in this area have mainly
      investigated the correlates self harm, or have been restricted to forensic
      services, within single hospitals. OBJECTIVES: To describe the demographic
      characteristics of those who self harm, and the characteristics of self harming
      behaviour within adult psychiatric wards across the UK. METHODS: Analysis of 500
      reports of self harm within inpatient services across England and Wales, randomly
      selected from a total of 14,271 reports collected by the National Patient Safety
      Agency. RESULTS: Most episodes of self harm were by women, and did not put the
      service user's life at risk. The most common form of self harm involved breaking
      the skin. Women were more likely to use methods of restricting their breathing,
      whilst men were more likely to use outwardly aggressive methods. Self harm was
      often a private act, which took place in bedrooms, bathrooms and toilets, and
      during the evening hours. Taking into account the numbers of beds within each
      service nationally, there were more episodes of self harm within forensic
      services. The most common interventions for self harm were verbal de-escalation,
      and manual restraint. The most common antecedents to self harm were a distressing
      psychological state, conflict behaviours (behaviours which threatened staff, or
      service user safety), and conflict with staff. CONCLUSIONS: Self harm within
      inpatient care constitutes a wide range of behaviours, and it may be useful for
      clinicians to discuss the particular meaning of the methods of self harm used
      with service users. In general, self harm is a private act, suggesting that most
      acts of self harm are not intended to have an impact on others. More research
      into the social nature of self harm, and the meaning of different self harming
      behaviours (particularly outwardly aggressive methods of self harm such as
      headbanging), would help to increase our understanding of these acts, and develop
      more appropriate ways of supporting service users. Future research should also
      investigate how staff behaviour may contribute to self harm. The development of a
      reporting system which requires a detailed account of incidents would aid future
      research in these areas.

PMID- 22609138
TI  - Value of information methods for planning and analyzing clinical studies optimize
      decision making and research planning.
AB  - OBJECTIVE: The results of two randomized clinical trials (RCTs) demonstrate the
      clinical effectiveness of alternatives to casting for certain ankle and wrist
      fractures. We illustrate the use of value of information (VOI) methods for
      evaluating the evidence provided by these studies with respect to decision
      making. STUDY DESIGN AND SETTING: Using cost-effectiveness data from these
      studies, the expected value of sample information (EVSI) of a future RCT can be
      determined. If the EVSI exceeds the cost of the future trial for any sample size,
      then the current evidence is considered insufficient for decision making and a
      future trial is considered worthwhile. If, on the other hand, there is no sample
      size for which the EVSI exceeds the cost, then the evidence is considered
      sufficient, and no future trial is required. RESULTS: We found that the evidence
      from the ankle study was insufficient to support the adoption of the removable
      device and determined the optimal sample size for a future trial. Conversely, the
      evidence from the wrist study was sufficient to support the adoption of the
      removable device. CONCLUSIONS: VOI methods provide a decision-analytic
      alternative to the standard hypothesis testing approach for assessing the
      evidence provided by cost-effectiveness studies and for determining sample sizes
      for RCTs.

PMID- 22609139
TI  - Commentary on: the "lost" NNT--Sadatsafavi et al.

PMID- 22609140
TI  - Treatment effects on patient-important outcomes can be small, even with large
      effects on surrogate markers.
AB  - OBJECTIVE: Surrogate markers are often used in clinical trials if too much time
      or expense is involved to observe the effect of treatment on patient-important
      outcomes. We wished to estimate the ultimate effects of treatment when randomized
      trials have addressed only a surrogate marker, and additional, independent
      studies evaluate the association between the surrogate and the final outcome.
      STUDY DESIGN AND SETTING: We show how to calculate the overall effect of
      treatment on a final outcome, together with its standard error and confidence
      interval. The methods are illustrated with data on the effect of therapy on
      hepatitis B seroconversion, a surrogate marker, and its association with patient
      important outcomes (cirrhosis and liver cancer). RESULTS: We find that the effect
      of treatment on the final outcome may be small even if there are strong
      associations between treatment and the surrogate and between the surrogate and
      the patient-important outcome. CONCLUSION: Apparently, robust treatment effects
      on surrogates are likely to lead to small and uncertain effects on patient
      important outcomes. We should be cautious in advising patients to adopt a therapy
      when compelling evidence is restricted to its impact on surrogate outcomes,
      particularly if that therapy may be toxic or otherwise cause harms.

PMID- 22609141
TI  - GRADE guidelines: 12. Preparing summary of findings tables-binary outcomes.
AB  - Summary of Findings (SoF) tables present, for each of the seven (or fewer) most
      important outcomes, the following: the number of studies and number of
      participants; the confidence in effect estimates (quality of evidence); and the
      best estimates of relative and absolute effects. Potentially challenging choices
      in preparing SoF table include using direct evidence (which may have very few
      events) or indirect evidence (from a surrogate) as the best evidence for a
      treatment effect. If a surrogate is chosen, it must be labeled as substituting
      for the corresponding patient-important outcome. Another such choice is
      presenting evidence from low-quality randomized trials or high-quality
      observational studies. When in doubt, a reasonable approach is to present both
      sets of evidence; if the two bodies of evidence have similar quality but
      discrepant results, one would rate down further for inconsistency. For binary
      outcomes, relative risks (RRs) are the preferred measure of relative effect and,
      in most instances, are applied to the baseline or control group risks to generate
      absolute risks. Ideally, the baseline risks come from observational studies
      including representative patients and identifying easily measured prognostic
      factors that define groups at differing risk. In the absence of such studies,
      relevant randomized trials provide estimates of baseline risk. When confidence
      intervals (CIs) around the relative effect include no difference, one may simply
      state in the absolute risk column that results fail to show a difference, omit
      the point estimate and report only the CIs, or add a comment emphasizing the
      uncertainty associated with the point estimate.

PMID- 22609142
TI  - Bringing next-generation therapeutics to the clinic through synthetic biology.
AB  - Recent advances in synthetic biology have created genetic tools with the
      potential to enhance the specificity, dynamic control, efficacy, and safety of
      medical treatments. Interfacing these genetic devices with human patients may
      thus bring about more efficient treatments or entirely new solutions to presently
      intractable maladies. Here we review engineered circuits with clinical potential
      and discuss their design, implementation, and validation.

PMID- 22609143
TI  - Can the modeling of herd immunity help design influenza immunization policy?

PMID- 22609144
TI  - Knowledge of energy balance guidelines and associated clinical care practices:
      the U.S. National Survey of Energy Balance Related Care among Primary Care
      Physicians.
AB  - OBJECTIVE: To assess primary care physicians' (PCPs) knowledge of energy balance
      related guidelines and the association with sociodemographic characteristics and
      clinical care practices. METHOD: As part of the 2008 U.S. nationally
      representative National Survey of Energy Balance Related Care among Primary Care
      Physicians (EB-PCP), 1776 PCPs from four specialties who treated adults (n=1060)
      or children and adolescents (n=716) completed surveys on sociodemographic
      information, knowledge of energy balance guidelines, and clinical care practices.
      RESULTS: EB-PCP response rate was 64.5%. For PCPs treating children, knowledge of
      guidelines for healthy BMI percentile, physical activity, and fruit and
      vegetables intake was 36.5%, 27.0%, and 62.9%, respectively. For PCPs treating
      adults, knowledge of guidelines for overweight, obesity, physical activity, and
      fruit and vegetables intake was 81.4%, 81.3%, 70.9%, and 63.5%, respectively.
      Generally, younger, female physicians were more likely to exhibit correct
      knowledge. Knowledge of weight-related guidelines was associated with assessment
      of body mass index (BMI) and use of BMI-for-age growth charts. CONCLUSION:
      Knowledge of energy balance guidelines among PCPs treating children is low, among
      PCPs treating adults it appeared high for overweight and obesity-related clinical
      guidelines and moderate for physical activity and diet, and was mostly unrelated
      to clinical practices among all PCPs.

PMID- 22609145
TI  - Broadening the phenotype associated with mutations in UPF3B: two further cases
      with renal dysplasia and variable developmental delay.
AB  - We present two brothers with mutations in UPF3B, an X-linked intellectual
      disability gene. Our family consists of two affected brothers and a carrier
      mother. Both affected brothers had renal dysplasia. A maternal uncle died from a
      congenital heart defect at 4 months. The two boys had variable degrees of
      developmental delay. One had macrocephaly, significant expressive speech delay
      and constipation. The other brother had normocephaly, obsessional tendencies and
      was diagnosed with high functioning autism. The phenotypically normal mother had
      100% skewed X-inactivation. Our cases expand the phenotype seen with UPF3B
      mutations and highlight the variability within families.

PMID- 22609146
TI  - Drought-induced modifications of photosynthetic electron transport in intact
      leaves: analysis and use of neural networks as a tool for a rapid non-invasive
      estimation.
AB  - Water deficit is one of the most important environmental factors limiting
      sustainable crop yields and it requires a reliable tool for fast and precise
      quantification. In this work we use simultaneously recorded signals of
      photoinduced prompt fluorescence (PF) and delayed fluorescence (DF) as well as
      modulated reflection (MR) of light at 820nm for analysis of the changes in the
      photosynthetic activity in detached bean leaves during drying. Depending on the
      severity of the water deficit we identify different changes in the primary
      photosynthetic processes. When the relative water content (RWC) is decreased to
      60% there is a parallel decrease in the ratio between the rate of excitation
      trapping in the Photosystem (PS) II reaction center and the rate of reoxidation
      of reduced PSII acceptors. A further decrease of RWC to 20% suppresses the
      electron transfer from the reduced plastoquinone pool to the PSI reaction center.
      At RWC below values 15%, the reoxidation of the photoreduced primary quinone
      acceptor of PSII, Q(A)(-), is inhibited and at less than 5%, the primary
      photochemical reactions in PSI and II are inactivated. Using the collected sets
      of PF, DF and MR signals, we construct and train an artificial neural network,
      capable of recognizing the RWC in a series of "unknown" samples with a
      correlation between calculated and gravimetrically determined RWC values of about
      R(2)~0.98. Our results demonstrate that this is a reliable method for
      determination of RWC in detached leaves and after further development it could be
      used for quantifying of drought stress of crop plants in situ. This article is
      part of a Special Issue entitled: Photosynthesis Research for Sustainability:
      from Natural to Artificial.

PMID- 22609147
TI  - Interleukin-33 and the function of innate lymphoid cells.
AB  - Interleukin (IL)-33 is a member of the IL-1 cytokine family that has been shown
      to play an important role in the induction and effector phases of type 2 immune
      responses. Both innate and adaptive immunity are regulated by IL-33, and many
      studies have shown disease-associated functions for this cytokine. Recently, IL
      33 has been implicated in the function of novel innate lymphocyte populations
      that regulate both protective responses in parasitic infections and allergic
      airway inflammation. Here, we discuss recent data highlighting the dual roles of
      IL-33 in protective and deleterious immune responses.

PMID- 22609149
TI  - Estimating typical, best-case and worst-case life expectancy scenarios for
      patients starting chemotherapy for advanced non-small-cell lung cancer: a
      systematic review of contemporary randomized trials.
AB  - INTRODUCTION: We sought to estimate life expectancy scenarios for patients
      starting chemotherapy for advanced non-small-cell lung cancer (NSCLC). METHODS:
      We searched for randomized first-line chemotherapy trials published from January
      2000 to April 2008. We recorded median time to progression (TTP) and median
      overall survival (OS) and extracted the following percentiles (represented
      scenario) from each OS curve: 90th (worst-case), 75th (lower-typical), 25th
      (upper-typical) and 10th (best-case). For each OS curve we divided these
      percentiles (scenarios) in turn by the median to determine if a simple
      relationship existed between each scenario and the median. RESULTS: From 60
      trials (29,657 patients), the mean for median TTP was 4.8 months (interquartile
      range [IQR] 4.0-5.3), the mean for median OS was 9.2 months (IQR 8.1-10.1) and
      the mean ratio for median OS to median TTP was 2.0 (IQR 1.7-2.2). The mean (IQR)
      in months for each OS scenario was: worst-case, 2.4 (1.9-2.7); lower-typical, 4.8
      (4.2-5.4); upper-typical, 16.3 (14.4-18.1); and best-case, 25 (21.0-28.0). The
      mean values (IQR) for each scenario divided by the median were: worst-case/median
      0.26 (0.21-0.29); lower-typical/median 0.53 (0.5-0.57); upper-typical/median 1.81
      (1.69-1.93) and best-case/median 2.84 (2.57-3.19). These values can be
      approximated by the simple multiples: 0.25, 0.5, 2 and 3. Independent predictors
      of longer OS were ECOG PS<2, adenocarcinoma, and longer TTP; all p-values<0.001.
      CONCLUSION: Simple multiples of an OS curve's median provided accurate estimates
      of typical (half to double the median), best-case (triple the median), and worst
      case (one quarter of the median) life expectancy scenarios for patients starting
      chemotherapy for advanced NSCLC.

PMID- 22609148
TI  - The otherness of self: microchimerism in health and disease.
AB  - Microchimerism (Mc) refers to the harboring of a small number of cells (or DNA)
      that originated in a different individual. Naturally acquired Mc derives
      primarily from maternal cells in her progeny, or cells of fetal origin in women.
      Both maternal and fetal Mc are detected in hematopoietic cells including T and B
      cells, monocyte/macrophages, natural killer (NK) cells and granulocytes. Mc
      appears also to generate cells such as myocytes, hepatocytes, islet beta cells
      and neurons. Here, the detrimental and beneficial potential of Mc is examined.
      The prevalence, diversity and durability of naturally acquired Mc, including in
      healthy individuals, indicates that a shift is needed from the conventional
      paradigm of 'self versus other' to a view of the normal 'self' as constitutively
      chimeric.

PMID- 22609150
TI  - Efficacy of florfenicol injection in the treatment of Mycoplasma hyopneumoniae
      induced respiratory disease in pigs.
AB  - This study investigated the efficacy of a single intramuscular injection of a new
      formulation of florfenicol to treat clinical respiratory disease following
      experimental Mycoplasma hyopneumoniae infection. M. hyopneumoniae-free piglets
      were allocated to three groups, namely, a treatment group (TG) and a positive
      control group (PCG), which were both inoculated endotracheally with a highly
      virulent isolate of M. hyopneumoniae, and a negative control group. At the onset
      of clinical disease, the TG received a single injection of florfenicol (30
      mg/kg). All pigs were euthanased 4 weeks post-infection. Clinical symptoms were
      significantly reduced in the TG in comparison with the PCG. Average daily gain,
      feed conversion ratio, mortality and lung lesions were improved in the TG
      compared to the PCG, but the differences were not statistically significant.

PMID- 22609151
TI  - The use of ciclosporin A in veterinary dermatology.
AB  - Ciclosporin A (CsA) has potent immunosuppressive and immunomodulatory activity
      that has been exploited in human medicine to prevent the rejection of
      transplanted organs and to manage atopic dermatitis and psoriasis. Over the past
      decade, CsA has been employed more frequently in veterinary dermatology and its
      value in the management of several canine and feline dermatoses is now well
      established. CsA inhibits calcineurin phosphatase, suppressing T cell activation
      and the synthesis of T cell cytokines consequently impairing the activity of B
      cells, antigen-presenting cells, mast cells, basophils and eosinophils. The
      pharmacokinetics of CsA are similar in humans, dogs and cats and the drug has a
      wide safety margin in dogs, cats and rabbits. Adverse effects, principally
      transient vomiting and soft faeces/diarrhoea, may be seen shortly after
      instituting treatment but often resolve despite continuing treatment. Gingival
      hyperplasia and cutaneous effects such as hirsutism may occur after prolonged
      treatment.

PMID- 22609152
TI  - Vaccination of pigs reduces Salmonella Typhimurium numbers in a model mimicking
      pre-slaughter stress.
AB  - In pigs, infection with Salmonella Typhimurium often results in the development
      of carriers that re-excrete the organism during periods of stress. Previous
      studies have shown that cortisol plays a significant role in the recrudescence of
      Salmonella Typhimurium and that re-excretion can be induced by injections of
      dexamethasone. This study evaluated whether a commercially available Salmonella
      Typhimurium vaccine was able to reduce Salmonella excretion in a model mimicking
      pre-slaughter stress. Pigs were randomly assigned to either vaccination or a
      control group and, 5 weeks later, were infected with Salmonella Typhimurium.
      Twenty-three days post infection, pigs were injected with dexamethasone to induce
      recrudescence and Salmonella Typhimurium numbers were determined. Salmonella
      loads were significantly lower in the ileum and colon and in the contents of the
      ileum and caecum in vaccinated pigs than in non-vaccinated pigs. In addition,
      significantly more Salmonella positive tonsil and colon samples were found in non
      vaccinated pigs. Vaccination with an attenuated vaccine reduced but did not
      eliminate Salmonella Typhimurium in pigs in conditions mimicking pre-slaughter
      stress.

PMID- 22609153
TI  - Effects of doxapram, prethcamide and lobeline on spirometric, blood gas and acid
      base variables in healthy new-born calves.
AB  - A number of drugs have been used to treat asphyxia in new-born calves and the aim
      of the current study was to investigate the effect of commonly-used stimulant
      drugs on ventilation, arterial blood gas and acid base variables. A group (n=18)
      of new-born (3-15 h old) calves were treated in a randomised sequence with
      doxapram (40 mg, IV), lobeline (5mg, IV) or prethcamide (5 mL, consisting of 375
      mg crotethamide and 375 mg cropropamide, buccally). Blood and spirometric
      measurements, using an ultrasonic spirometer, were collected prior to and 1, 5,
      15, 30, 60, 90 min after administration of each drug. Doxapram caused a
      significant increase in the respiratory rate, peak inspiratory and expiratory
      flow and minute volume (V(min)) during the 90-min post-treatment study period,
      although maximum values occurred 1 min after treatment. The V(min) increased from
      13.8 +/- 5.0 L to 28.5 +/- 12.3 L. Prethcamide, but not lobeline, also caused
      significant increases in inspiratory and expiratory volumes. The effects of
      doxapram on ventilation were accompanied by an increase in arterial partial
      pressure of oxygen (P(a)O(2)) (77.7 +/- 18.8 mm Hg to 93.2 +/- 23.7 mm Hg), a
      decrease in arterial partial pressure of carbon dioxide (P(a)CO(2)) (42.6 +/- 4.9
      mm Hg to 33.1 +/- 6.6mm Hg), a significant increase in pH and a decrease in
      bicarbonate concentration and base excess 1 min after treatment. Prethcamide
      caused a gradual increase in P(a)O(2) and decrease in P(a)CO(2) over 90 min,
      whereas lobeline had no measurable effect on the investigated variables. Of the
      three treatments, only doxapram had a distinct stimulatory effect on respiration
      in healthy neonatal calves and may therefore be useful in the treatment of calf
      asphyxia.

PMID- 22609154
TI  - Assessment of the antidiarrhoeal properties of the aqueous extract, the 80%
      methanol extract and its soluble fractions of the leaves of Alstonia congensis
      Engl. (Apocynaceae) in Wistar rats.
AB  - AIM OF THE STUDY: To evaluate the antidiarrhoeal properties of Alstonia congensis
      leaves claimed to be effective for the treatment of diarrhoea by traditional
      healers during our ethnopharmacological investigation conducted in Kinshasa,
      Democratic Republic of Congo. MATERIALS AND METHODS: The aqueous extract
      (decoction), and the 80% hot methanol extract (Soxhlet extraction) were obtained.
      This last extract was fractionated. The antidiarrhoeal activity was evaluated
      using castor oil and magnesium sulphate-induced diarrhoea in animals. The
      potential antibacterial activity of all samples was also assessed in vitro.
      RESULTS: At all oral doses of 100 and 200 mg/kg body weight, all A. congensis
      samples showed significant and dose-dependent antidiarrhoeal activity in treated
      Wistar rats characterised by significant increase of onset time and decrease of
      all other diarrhoeal parameters at various degrees compared to untreated groups
      in both models. At the highest oral dose of 200 mg/kg bodyweight, the 80% hot
      methanol and aqueous extracts produced 79.8 +/- 2.1% and 78.6 +/- 0.5%, and 75.0
      +/- 2.1% and 71.4 +/- 2.1% inhibition of defecation and diarrhoea respectively
      against castor oil-induced diarrhoea, and 75.0 +/- 1.2% and 73.3+/-1.2%
      inhibition of diarrhoea respectively against magnesium sulphate-induced
      diarrhoea. The 80% hot methanol and aqueous detannified extracts showed low
      activity (42-47% inhibition of defecation and/or diarrhoea in both tests)
      suggesting that tannins may be responsible for the observed activity. At the same
      oral doses, the total alkaloid extract, the chloroform soluble fraction rich in
      alkaloids, the 80% methanol and the alkaline aqueous soluble subfractions
      produced more than 50% inhibition of defecation and/or diarrhoea in both tests.
      From the antibacterial testing in vitro, results indicated that all A. congensis
      samples exhibited an antibacterial activity mainly against bacteria implicated in
      diarrhoea with MIC and MBC values in the range of 15.6-500 MUg/ml. The most
      active samples were the aqueous (decoction) and the 80% hot methanol dried
      extracts, the chloroform subfraction rich in alkaloids and the total alkaloid
      extract (MIC: 15.7-125 MUg/ml, MBC: 31.2-250 MUg/ml). Proteus varibilis was found
      to be the most resistant microorganism. CONCLUSION: These reported results can
      partly support and justify the traditional use of extracts from Alstonia
      congensis leaves for the treatment of diarrhoea in tradittional medicine.

PMID- 22609156
TI  - The obesity paradox: methodological considerations based on epidemiological and
      clinical evidence--new insights.
AB  - Despite the well-known association of obesity with increased mortality and the
      development of chronic diseases, an "obesity paradox" has been reported in
      several patient categories; i.e., overweight and obese patients have a better
      prognosis than normal or low-weight individuals. The present review aims to
      identify potential factors lying beneath the beneficial effect of overweight and
      obesity. In particular, the role of nutritional status, malnutrition and
      catabolic state, as well as intentional vs. unintentional weight loss and the
      possibility of a U-shape relationship between body mass index and survival will
      be examined. Furthermore, methodological considerations framing the obesity
      paradox will be presented and discussed.

PMID- 22609155
TI  - Antiparasitic compounds from Cornus florida L. with activities against Plasmodium
      falciparum and Leishmania tarentolae.
AB  - AIM OF THE STUDY: The objective of this study was to identify the antiplasmodial
      constituents from the bark of Cornus florida L., a plant traditionally used in
      North America for the treatment of malaria. METHODS AND MATERIALS: Dried and
      powdered bark was extracted with 95% ethanol. The resultant extract was subjected
      to in vitro antiplasmodial-guided fractionation against Plasmodium falciparum
      (D10 strain). Antiplasmodial IC(50) values were calculated for pure compounds.
      Compounds were also assayed against Leishmania tarentolae, and rat skeletal
      myoblast L6 cells to assess antileishmanial activity and cytotoxicity,
      respectively. RESULTS: Antiplasmodial-guided fractionation afforded 8 compounds:
      betulinic acid (1), ursolic acid (2), beta-sitosterol (3), ergosta-4,6,8,22
      tetraene-3-one (4), 3beta-O-acetyl betulinic acid (5), 3-epideoxyflindissol (6),
      3beta-O-cis-coumaroyl betulinic acid (7), 3beta-O-trans-coumaroyl betulinic acid
      (8), of which, (6) is for the first time here isolated from a natural product and
      (4), (7) and (8) are reported for the first time from this genus. In vitro IC(50)
      values against P. falciparum for (4) (61.0 MUM) (6) (128.0 MUM), (7) (10.4 MUM),
      (8) (15.3 MUM) are reported for the first time. Antileishmanial IC(50) values are
      reported here for the first time for (4) (11.5 MUM), (6) (1.8 MUM), (7) (8.3 MUM)
      and (8) (2.2 MUM). Cytotoxicity against L6 cells is reported for all compounds.
      CONCLUSIONS: The compounds isolated in this study, while displaying moderate in
      vitro antiplasmodial activity, do not fully support the historical importance of
      C. florida as an antimalarial remedy in North America. The traditional remedy may
      exert its well documented effects by mechanisms unrelated to direct
      antiplasmodial action. While not traditionally used to treat Leishmania, this
      work shows that several constituents of C. florida possess promising in vitro
      antileishmanial activity.

PMID- 22609157
TI  - The effect of whole body vibration on balance, mobility and falls in older
      adults: a systematic review and meta-analysis.
AB  - This systematic review aimed to examine the effect of WBV on balance, mobility
      and falls among older adults. The databases used included MEDLINE, the Excerpta
      Medica database, the Cumulative Index to Nursing and Allied Health Literature,
      the Cochrane Library Databases of Systematic Reviews, Physiotherapy Evidence
      Database (PEDro), PubMed, and Science Citation Index (last search in October
      2011). Randomized controlled trials that investigated the effect of WBV on
      balance, mobility or falls in older adults were included in this review. The
      PEDro score was used to examine the methodological quality of the selected
      studies. The effect of WBV on balance, mobility and fall-related outcomes were
      extracted. The data extraction and rating were performed by a researcher and the
      results were confirmed by the principal investigator. Meta-analysis was done if 3
      or more studies measured the same outcome of interest. Among 920 articles
      screened, fifteen articles (thirteen trials) satisfied the criteria and were
      included in this review. Methodological quality was good for six of the studies
      (PEDro score=6-7). Meta-analysis revealed that WBV has a significant treatment
      effect in Tinetti Total Score (p<0.001), Tinetti Body Balance Score (p=0.010) and
      Timed-Up-and-Go test (p=0.004). No significant improvement was noted in Tinetti
      Gait Score after WBV training (p=0.120). The effect of WBV on other
      balance/mobility outcomes and fall rate remains inconclusive. To conclude, WBV
      may be effective in improving relatively basic balance ability and mobility among
      older adults, particularly frailer ones. More good-quality WBV trials are
      required.

PMID- 22609158
TI  - Beat-to-beat variability of repolarization as a new biomarker for proarrhythmia
      in vivo.
AB  - Pharmacological safety evaluation of (pro) drugs includes cardiac safety
      assessment of proarrhythmic liability in healthy tissue with emphasis on the
      rapid component of the delayed rectifier (I(Kr)). The lack of (1) an arrhythmic
      end point, (2) tests in remodeled, predisposed tissue, and (3) testing chronic
      drug influence on channel trafficking impairs on the drawn conclusions of these
      assays regarding drug safety. Moreover, the currently used human ether-a-go-go
      related gene assays, action potential duration, prolongation in multicellular
      preparations, or the QT interval have significant shortcomings in their
      prediction of an increased risk for drug-induced torsades de pointes arrhythmia.
      In this review, it will be proposed that beat-to-beat variability of
      repolarization quantified as short-term variability can (1) discriminate between
      safe and unsafe drugs even under predisposed and highly arrhythmogenic conditions
      despite accompanying QT prolongation and (2) identify the individual at risk for
      subsequent arrhythmic events.

PMID- 22609159
TI  - A stimulating environment for the atrial kick: spinal cord stimulation can
      inhibit atrial fibrillation.

PMID- 22609160
TI  - Grp1 plays a key role in linking insulin signaling to glut4 recycling.
AB  - The glucose transporter type 4 (glut4) is critical for metabolic homeostasis.
      Insulin regulates glut4 by modulating its expression on the cell surface. This
      regulation is mainly achieved by targeting the endocytic recycling of glut4. We
      identify general receptor for 3-phosphoinositides 1 (Grp1) as a guanine
      nucleotide exchange factor for ADP-ribosylation factor 6 (ARF6) that promotes
      glut4 vesicle formation. Grp1 also promotes the later steps of glut4 recycling
      through ARF6. Insulin signaling regulates Grp1 through phosphorylation by Akt. We
      also find that mutations that mimic constitutive phosphorylation of Grp1 can
      bypass upstream insulin signaling to induce glut4 recycling. Thus, we have
      uncovered a major mechanism by which insulin regulates glut4 recycling. Our
      findings also reveal the complexity by which a single small GTPase in vesicular
      transport can coordinate its multiple steps to accomplish a round of transport.

PMID- 22609162
TI  - Serum biomarker in neurofibromatosis type 1.

PMID- 22609163
TI  - In-line cold column trapping of organic phase in dispersive liquid-liquid
      microextraction: enrichment and determination of curcumin in human serum.
AB  - A new temperature controlled cold column trapping (CCT) system was developed for
      in-line sequestration of organic phase in dispersive liquid-liquid
      microextraction (DLLME) method. In the developed CCT-DLLME method, the dispersed
      organic extraction phase is solidified and trapped in the CCT, packed with glass
      particles. Subsequently, the sequestered phase is washed out in an elevated
      temperature by using an appropriate solvent. The column temperature is controlled
      by a pair of thermal electric cooler (TEC) plates. The new device is simple and
      portable and can eliminate the need for centrifugation in the DLLME method for
      solvents with an appropriate melting point. Some important parameters such as
      types of extraction and disperser solvents and their volumes, minimum and maximum
      column temperatures and extraction time were optimized for the extraction of
      curcumin, as a model compound. Using 1-dodecanol as the organic solvent and
      acetone as the disperser, recoveries exceeding 90% and a relative standard
      deviation of 2.87% were obtained for 5 replicated analyses of curcumin by an HPLC
      method. The detection limit of curcumin (3sigma) extracted by the CCT-DLLME
      system was 28 MUg L-1. The method was successfully applied to the determination
      of curcumin in some human serum samples.

PMID- 22609161
TI  - Transcriptional dominance of Pax7 in adult myogenesis is due to high-affinity
      recognition of homeodomain motifs.
AB  - Pax3 and Pax7 regulate stem cell function in skeletal myogenesis. However,
      molecular insight into their distinct roles has remained elusive. Using gene
      expression data combined with genome-wide binding-site analysis, we show that
      both Pax3 and Pax7 bind identical DNA motifs and jointly activate a large panel
      of genes involved in muscle stem cell function. Surprisingly, in adult myoblasts
      Pax3 binds a subset (6.4%) of Pax7 targets. Despite a significant overlap in
      their transcriptional network, Pax7 regulates distinct panels of genes involved
      in the promotion of proliferation and inhibition of myogenic differentiation. We
      show that Pax7 has a higher binding affinity to the homeodomain-binding motif
      relative to Pax3, suggesting that intrinsic differences in DNA binding contribute
      to the observed functional difference between Pax3 and Pax7 binding in
      myogenesis. Together, our data demonstrate distinct attributes of Pax7 function
      and provide mechanistic insight into the nonredundancy of Pax3 and Pax7 in muscle
      development.

PMID- 22609164
TI  - Enhancing IgG purification from serum albumin containing feedstock with
      hydrophobic charge-induction chromatography.
AB  - Hydrophobic charge-induction chromatography (HCIC) with 4-mercaptoethyl-pyridine
      (MEP) as the ligand is a novel technology for antibody purification, however, the
      separation selectivity still needs to be improved for the applications,
      especially for the impurity of serum albumin. In this study, with bovine serum
      immunoglobulin G (IgG) as the model, the purification of IgG from the serum
      albumin containing feedstock was developed with the commercial HCIC resin MEP
      HyperCel, focusing on the optimization of operation pH and salt addition. The
      adsorption isotherms of IgG and bovine serum albumin (BSA) were investigated at
      different pHs, and the binding and elution behaviors of two proteins in the
      column were also studied at varying pHs. In addition, the protein-ligand
      interactions were investigated with some additives in the buffer. It was found
      that the conditions of pH 6 with 0.1 M NaCl or pH 8 could be used to effectively
      remove BSA from the MEP resin without the influence on IgG adsorption. Two modes
      with control of loading or washing buffer were tested to enhance the purification
      of IgG from BSA containing feedstock, and the purity of IgG was improved to about
      95% compared with 62.9% for the control. The results demonstrated that the
      control of loading pH or the addition of NaCl in the buffer might be an effective
      method to improve the purification of antibody with the HCIC process.

PMID- 22609165
TI  - Effects of selected parameters on the response of the evaporative light
      scattering detector in supercritical fluid chromatography.
AB  - Due to the renewal of the use of supercritical fluid chromatography (SFC), the
      coupling of SFC with evaporative light scattering detection (ELSD) needs to be
      revisited. Indeed, SFC and ELSD apparatus have evolved, while understanding of
      the nebulisation process has improved. This detector, first developed for polymer
      analyses can be used for a lot of compounds that do not display sufficient UV
      absorption. Because the response of ELSD is related to numerous parameters, such
      as mobile phase composition, the velocity difference between the mobile phase and
      the nebulisation gas, or the nebulisation temperature, many additional studies
      are necessary to understand its behaviour in SFC as compared to HPLC. The effects
      of the nature of co-solvent added to carbon dioxide (methanol, ethanol and
      acetonitrile), the injected volume and the flow rate on the ELSD response were
      studied. Certain parameters induce great changes on the nebulisation recovery
      (the proportion of mobile phase entering the drift tube), allowing for a dramatic
      improvement in peak area. Moreover, effects of the particle size in the aerosol
      were also observed, related, as expected, to the modifier nature, but strangely
      also to the injected volume. Specific and positive behaviour of the ELSD
      detection on the apparent peak efficiency was confirmed in SFC, for large
      injected volumes. Finally, a flow rate increase reduces peak area, showing that
      the use of high flow rates, although attractive to shorten analysis duration, is
      not favourable to ELSD response. Numerous parameters acting on detector response
      are modified by the flow rate change, such as the mobile phase velocity.
      Moreover, measurement of the nebulisation chamber temperature shows the strong
      decrease of temperature for high flow rates, due to the supercritical fluid
      depressurisation.

PMID- 22609166
TI  - Multiple headspace-solid-phase microextraction as a powerful tool for the
      quantitative determination of volatile radiolysis products in a multilayer food
      packaging material sterilized with gamma-radiation.
AB  - A method consisting of multiple headspace solid-phase microextraction followed by
      gas chromatography-mass spectrometry analysis was developed and used to determine
      the main volatile radiolysis products formed by gamma-irradiation of flexible
      multilayer food packaging samples. The developed method allows the use of solid
      phase microextraction in the quantification of compounds from plastic solid
      samples. A screening of volatiles in the gamma-irradiated and non-irradiated
      films was performed and 29 compounds were identified in the irradiated packaging,
      17 of which were absent in the non-irradiated samples. The main volatile
      radiolysis products identified were: 1,3-di-tert-butylbenzene; 2,6-di-tert-butyl
      1,4-benzoquinone; 4-tert-butyl-phenol and the off-odor compounds butanoic acid
      and valeric acid. These volatile radiolysis compounds were determined with the
      proposed method and the results are shown and discussed. Solid-liquid extraction
      and headspace solid-phase microextraction methods were also studied for
      comparative purposes. The automated solvent-free multiple HSPME technique here
      presented can be used to quantify the radiolysis compounds in irradiated plastic
      solid samples in a simple way with the advantages of being free from matrix
      influence and environmentally friendly.

PMID- 22609167
TI  - Chromatographic purification and characterization of whey protein-dextran
      glycation products.
AB  - A process for the food-grade preparative-scale production and chromatographic
      purification of whey protein isolate (WPI)-dextran glycates was developed in this
      work. The Maillard reaction was used to produce the glycates in aqueous solution.
      A 5 mL cation exchange column and salt step gradients were utilized to elute the
      glycated protein at low salt and unreacted protein at high salt. The process was
      scaled-up 160-fold to an 800 mL column. Glycated products were analyzed by SDS
      PAGE, BCA protein assay and glycoprotein carbohydrate estimation kit, MALDI-TOF
      and static and dynamic light scattering. Glycated protein was relatively pure,
      containing only traces of beta-lactoglobulin, and it was heterogeneous due to
      oligo-glycation. It had a molecular mass of 26-35 kDa by static light scattering,
      and 22-67 kDa by MALDI-TOF. Mono-glycated protein would have been 23.8 kDa from
      beta-lactoglobulin (18.6 kDa) and dextran (5.2 kDa). This work demonstrated the
      utility of cation exchange chromatography for the large-scale purification of
      glycated proteins using food-grade chemicals and procedures.

PMID- 22609168
TI  - Purification of berry flavonol glycosides by long-bed gel permeation
      chromatography.
AB  - While Sephadex LH-20 gel is frequently employed as a stationary phase during pre
      separations and in open column chromatography systems, its separation power in
      long-bed gel permeation chromatography (GPC) applications is much less prevalent.
      Aimed at the characterization of bioactive constituents, a long-bed GPC protocol
      was established for lingonberry juice concentrate. The method included pre
      fractionation over HP-20 resin to eliminate sugars and organic acids as well as a
      major part of other predominant berry flavonoids (anthocyanins, flavan-3-ols and
      proanthocyanidins), prior to the elution of the fraction containing 10% (w/w) of
      quercetin glycosides (QGs). Subsequently, seven major QGs were purified using a
      10-m Sephadex LH-20 system and isocratic elution with methanol. The total mass
      recovery was 99.3+/-1.4%, after eluting the highly-retained compounds from the
      employed pre-column with 70% acetone. Injecting 1070 mg per run, the yield of
      purified QGs ranged from 2 to 6 mg per collected single fraction. The LC-UV/PDA
      purities of isolated Q-3-O-alpha-rhamnoside and Q-3-O-beta-galactoside were 82
      and 94 area% at 250 nm, while the three Q-pentosides showed purities of 59, 30,
      and 57 area%. By comparison, purity assessment of these isolates by quantitative
      1H NMR (total integral and modified 100% method) led to significantly lower
      purities of 70 and 52% for Q-rha and Q-gal and 38, 25 and 46% for Q-pentosides,
      respectively. This can be explained by the presence of hidden residual complexity
      (RC), which is revealed by the quantitative NMR method. This finding has
      potentially broader implication as it reveals an unexpected degree of RC in GPC
      fractions. Despite remarkable separation power for congeneric flavonoids, long
      bed GPC on Sephadex LH-20 produces materials, which require careful analysis of
      purity before interpreting bioassay results.

PMID- 22609169
TI  - Neutrality without incoherence: a response to Clark.

PMID- 22609170
TI  - Connexins in atherosclerosis.
AB  - Atherosclerosis, a chronic inflammatory disease of the vessel wall, involves
      multiple cell types of different origins, and complex interactions and signaling
      pathways between them. Autocrine and paracrine communication pathways provided by
      cytokines, chemokines, growth factors and lipid mediators are central to
      atherogenesis. However, it is becoming increasingly recognized that a more direct
      communication through both hemichannels and gap junction channels formed by
      connexins also plays an important role in atherosclerosis development. Three main
      connexins are expressed in cells involved in atherosclerosis: Cx37, Cx40 and
      Cx43. Cx37 is found in endothelial cells, monocytes/macrophages and platelets,
      Cx40 is predominantly an endothelial connexin, and Cx43 is found in a large
      variety of cells such as smooth muscle cells, resident and circulating leukocytes
      (neutrophils, dendritic cells, lymphocytes, activated macrophages, mast cells)
      and some endothelial cells. Here, we will systematically review the expression
      and function of connexins in cells and processes underlying atherosclerosis. This
      article is part of a Special Issue entitled: The Communicating junctions, roles
      and dysfunctions.

PMID- 22609171
TI  - Cancer research, a field on the verge of a paradigm shift?
AB  - The theoretical framework for the field of cancer research is based on two main
      principles. The first is that cancer advances in a stepwise manner, with each
      alteration driving cells further toward a malignant state. Second, to cure cancer
      we must target only cancer-specific properties. Here, we analyze the birth and
      propagation of the cancer research paradigm. We believe the current paradigm is
      immersed in crisis and that the field would benefit from integrating theories
      within and outside the normal modes of research to compile a new framework, with
      the hope of faster progress and significantly fewer cancer-related deaths.

PMID- 22609173
TI  - The role of odontogenic genes and proteins in tooth epithelial cells and their
      niche cells during rat tooth root development.
AB  - OBJECTIVES: The rodent incisor cervical loop and molar Hertwig's epithelial root
      sheath (HERS) are common models used for investigating tooth root generation. The
      purpose of the present study was to gain a better understanding of the molecular
      mechanisms mediating root development by determining the distinctive gene and
      protein expression profiles of each during different stages of development.
      METHODS: In this study, we used quantitative real time reverse transcription-PCR
      and immunohistochemistry to analyse the expression levels of high mobility group
      AT-hook 2, ameloblastin, amelogenin, dentine sialoprotein, dentine matrix protein
      1, osteocalcin, and bone sialoprotein in rat epithelial and mesenchymal cells
      isolated at postnatal days 4 and 8. RESULTS: Results showed that the expression
      of these genes and proteins was up-regulated in cervical loop epithelial cells,
      but decreased or unchanged in other cells during development. This increase in
      expression in the incisor cervical loop may be due to the interaction of the
      inner incisor dental papilla cells, which are the niche cells of cervical loop
      epithelial cells and demonstrated up-regulated expression of the corresponding
      proteins, revealing a complex and dynamic interplay of these molecules during
      neonatal tooth development. CONCLUSION: These findings provide novel insights
      into the molecular processes underlying crown development of rodent incisors, and
      contribute to our overall understanding of the pathogenic processes of tooth root
      dysontogenesis.

PMID- 22609172
TI  - Identification of a protein-containing enamel matrix layer which bridges with the
      dentine-enamel junction of adult human teeth.
AB  - OBJECTIVE: To investigate the ultrastructure and chemical composition of the
      dentine-enamel junction and adjacent enamel of minimally processed third molar
      tooth sections. DESIGN: Undecalcified human third molar erupted teeth were
      sectioned and etched with 4% EDTA or 37% phosphoric acid prior to visualization
      by scanning electron microscopy. Confocal Raman spectroscopy was carried out at
      50 MUm and more than 400 MUm away from the dentine-enamel junction before and
      after mild etching. RESULTS: A novel organic protein-containing enamel matrix
      layer was identified for the first time using scanning electron microscopy of
      etched bucco-lingual sections of crowns. This layer resembles a three-dimensional
      fibrous meshwork that is visually distinct from enamel "tufts". Previous studies
      have generally used harsher solvent conditions which likely removed this layer
      and precluded its prior characterization. The shape of the organic enamel layer
      generally reflected that of sheath regions of enamel rods and extended from the
      dentine-enamel junction about 100-400 MUm into the cuspal enamel. This layer
      exhibited a Raman CH stretching peak at ~2931 cm(-1) characteristic of proteins
      and this signal correlated directly with the presence and location of the matrix
      layer as identified by scanning electron microscopy. CONCLUSIONS: The enamel
      protein layer was most prominent close to the dentine-enamel junction and was
      largely absent in cuspal enamel >400 MUm away from the dentine enamel junction.
      We hypothesize that this protein containing matrix layer could provide an
      important biomechanical linkage between the enamel and the dentine-enamel
      junction and by extension, with the dentine, of the adult tooth (246 words).

PMID- 22609174
TI  - Simplified scaphoid reconstruction technique with Zaidemberg's vascularized
      radial graft.
AB  - For more than 10 years, we have been using a simplified reconstruction technique
      for scaphoid non-unions that involves the use of a graft first described by
      Zaidemberg et al. [1]. This approach requires that an island bone graft harvested
      from the radial styloid and pedicled on the 1,2-intercompartmental
      supraretinacular artery be embedded into the site of the non-union. The objective
      of our technical modifications was to simplify the harvesting and handling of the
      graft and the internal fixation. This technique is only used for cases of
      scaphoid non-union with avascular changes in the proximal fragment, repeated non
      union after bone grafting and internal fixation, chronic non-union with
      osteophyte formation in the dorso-radial aspect and fracture secondary to Preiser
      disease.

PMID- 22609175
TI  - Mazabraud's syndrome. A case with multiple myxomas.
AB  - Mazabraud's syndrome is defined as the combination of one or more intramuscular
      myxomas and fibrous dysplasia of bone. The diagnosis is important given the
      increased risk of malignant transformation of the bone lesions. We report a case
      in a 56-year-old patient with a 14-year follow-up during which multiple surgical
      procedures were required to remove myxomas (present at more than 15 sites). The
      resected myxomas were large and progressive. Unique features in this case include
      the long follow-up and the number of myxomas considerably above the average for
      this disease. Eighty other cases of Mazabraud's syndrome have been reported. The
      condition predominantly affects middle-aged women (mean age, 44 years). The bone
      lesions may be monostotic or polyostotic. Mazabraud's syndrome may be difficult
      to distinguish from soft-tissue sarcoma or neurofibromatosis. Identification of
      the underlying genetic abnormality provides diagnostic confirmation, as shown in
      our patient. The management consists in surgery to remove the myxomas and
      magnetic resonance imaging at regular intervals to monitor the lesions.

PMID- 22609177
TI  - The Oxford Knee Score: compared performance before and after knee replacement.
AB  - BACKGROUND: Self-administered quality-of-life questionnaires are now crucial to
      the evaluation of orthopaedic surgical patient-reported outcomes, as they reflect
      patient satisfaction. The Oxford Knee Score (OKS) is a validated instrument that
      is widely used to assess outcomes of knee osteoarthritis surgery. HYPOTHESIS: The
      relevance of the OKS (comprehension and relevance of the items and responses, and
      internal and external validity) and its discriminating performance measured based
      on the ceiling and floor threshold effects are better before than after knee
      replacement surgery. MATERIALS AND METHODS: We included 200 patients (100
      scheduled for knee replacement and 100 having had knee replacement more than 1
      year earlier). The OKS questionnaire was handed to each patient during the first
      surgeon visit or during a follow-up visit. The American Knee Society (AKS) score
      was determined simultaneously. RESULTS: The mean OKS was 43.7 (range, 21-56; SD,
      6.9) before surgery and 20.5 (range, 12-45; SD, 5.6) after surgery. The floor
      effect was absent (0%) before surgery and substantial (33%) after surgery; a weak
      ceiling effect (7%) was noted before surgery and no ceiling effect after surgery.
      Internal consistency of the OKS was excellent. The OKS correlated negatively with
      the AKS knee and functional scores, both before and after surgery. DISCUSSION:
      The OKS is well-suited to the evaluation of knee function both before and after
      knee replacement surgery. Before surgery, the absence of substantial floor and
      ceiling effects lead to excellent discrimination. After surgery, the substantial
      floor effect limits the ability to discriminate among the best results. Efforts
      should be made to develop more demanding scoring systems. LEVEL OF EVIDENCE:
      Level 2. Exploratory cohort study with universally applied reference standards.

PMID- 22609176
TI  - Is it worth fixing proximal humeral fractures at increased vascular risk?
AB  - OBJECTIVE: To evaluate fixation of proximal humeral fractures by anterograde
      nailing, in terms of fracture reduction, bone healing; osteonecrosis; functional
      consequences of osteonecrosis and malunion. DESIGN: Prospective, consecutive,
      multicenter based. SETTING: Academic Trauma Centers; approval was received from
      the ethics committee of the institutions involved in the study. METHODS: Fifty
      one patients were enrolled prospectively, with 31 3-part and 20 4-part displaced
      fractures (head displacement greater than 45 degrees , tuberosity-head gap
      greater than 10mm, diaphyseal gap greater than 10mm). A TelegraphTM nail (FH
      Orthopedics, Heimsbrunn, France) was the fixation device used, introduced through
      a superolateral transdeltoid approach under fluoroscopic guidance. The assessment
      included Simple Shoulder Test, absolute Constant score, X-rays every 3 months and
      CT-scan at final evaluation. Twelve patients died and one was lost to follow-up.
      Immediate complications included secondary displacement in four patients.
      RESULTS: There were no infections, no deltoid muscle or axillary nerve damage,
      and all the fractures united. After a mean follow-up of 24.1 months, malunion was
      observed in 29% of the remaining 38 patients and osteonecrosis in 32%. Both
      complications were more frequent and extensive in patients with 4-part fractures.
      The osteonecrosis area influenced the Constant score, which was 55.8 points when
      the area was less than 30%, 50.6 points between 30 and 50%, and 38 points when
      larger than 50%. Head malunion affected the Simple Shoulder Test and the Constant
      score. CONCLUSION: Nailing may thus be recommended for 3-part fractures, because
      osteonecrosis is less frequent, more focused, and better tolerated in this sub
      group. In contrast, antegrade nailing was not more beneficial than other internal
      fixation techniques for preventing osteonecrosis or head malunion in patients
      with 4-part fractures. LEVEL OF EVIDENCE: Level IV: prospective study.

PMID- 22609178
TI  - Heart-lung interactions and pulmonary buffering: lessons from a computational
      modeling study.
AB  - Our objective was to separate mechanical effects on the circulation that are due
      to increases in pleural pressure (Ppl) from those due to increases in
      transpulmonary pressure (Ptp). We used a computational model of the circulation
      (Magder et al., 2009) which includes four static elastic compartments (systemic
      and pulmonary arteries and veins) and two time-varying elastances to represent
      the ventricles. Changes in Ppl were modeled by increasing pressure in all
      thoracic compartments and changes in Ptp by increasing the pressure around the
      pulmonary venous compliant region. When Ptp was >pulmonary venous pressure (Pvp)
      a switch function created the equivalent of West zone II in pulmonary vessels.
      Cyclic increases in Ppl or Ptp produced systolic arterial pressure variations
      (SPV). However, with Ppl systolic pressure fell during expiration and average
      pulmonary venous pressure (Pvp) decreased, whereas with cyclic Ptp systolic
      pressure fell during inspiration and average Pvp increased. Increases in
      pulmonary vascular volume reduced SPV due to cyclic Ppl, which we call pulmonary
      buffering, but not in those due to cyclic changes in Ptp. In conclusion, cyclic
      increases in Ptp produce volume sensitive SPV whereas cyclic changes in Ptp
      produce non-volume responsive SPV. Cyclic Ppl decrease whereas cyclic Ptp
      increase pulmonary vascular volume.

PMID- 22609179
TI  - The measurement of carboxyhemoglobin and methemoglobin using a non-invasive pulse
      CO-oximeter.
AB  - The pulse CO-oximeter (Rad-57 Masimo Corporation, Irvine, CA) allows non-invasive
      and instantaneous measurement of carboxyhemoglobin (COHb) and methemoglobin
      (MetHb) percentage level using a finger probe. However, the accuracy and
      reliability of the Rad-57 against the gold standard of venous or arterial blood
      samples have not been clearly established. Thus, the objective of this trial is
      to evaluate the accuracy and precision of the Rad-57 pulse CO-oximeter by
      comparing it with venous sampling on the same subjects. Nine healthy subjects
      were subjected to carbon monoxide such that it raised the COHb to 10-14% on two
      different days and pooled together. The COHb and MetHb were measured with a blood
      gas-analyzer and simultaneously with the Rad-57 as the COHb increased from 1.4 to
      14%. Results were compared using linear regression and a Bland and Altman method
      comparison. Mean bias and precision for COHb measured with the Rad-57 was -1% and
      2.5%, respectively. The mean bias and precision for MetHb measured with the Rad
      57 was 0.0% and 0.3%, respectively. The ability to detect a COHb >= 10% occurred
      in 54% of the samples in which COHb was >= 10-14%. In conclusion, the Rad-57
      provides a reading that is between -6% and +4% of the true COHb value for 95% of
      all samples. The Rad-57 seems to be a good substitute as a first screening test
      of COHb when the pulse CO-oximeter reads <15%.

PMID- 22609180
TI  - WITHDRAWN: Development of an RT-PCR-RFLP assay for the detection and
      differentiation of wild-type and vaccine strains of classical swine fever virus.
AB  - This article has been withdrawn at the request of the author(s). The Publisher
      apologizes for any inconvenience this may cause. The full Elsevier Policy on
      Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 22609181
TI  - Importance of the Candida albicans cell wall during commensalism and infection.
AB  - An imbalance of the normal microbial flora, breakage of epithelial barriers or
      dysfunction of the immune system favour the transition of the human pathogenic
      yeast Candida albicans from a commensal to a pathogen. C. albicans has evolved to
      be adapted as a commensal on mucosal surfaces. As a commensal it has also
      acquired attributes, which are necessary to avoid or overcome the host defence
      mechanisms. The human host has also co-evolved to recognize and eliminate
      potential fungal invaders. Many of the fungal genes that have been the focus of
      this co-evolutionary process encode cell wall components. In this review, we will
      discuss the transition from commensalism to pathogenesis, the key players of the
      fungal cell surface that are important for this transition, the role of the
      morphology and the mechanisms of host recognition and response.

PMID- 22609182
TI  - Dual purpose microalgae-bacteria-based systems that treat wastewater and produce
      biodiesel and chemical products within a biorefinery.
AB  - Excess greenhouse gas emissions and the concomitant effect on global warming have
      become significant environmental, social and economic threats. In this context,
      the development of renewable, carbon-neutral and economically feasible biofuels
      is a driving force for innovation worldwide. A lot of effort has been put into
      developing biodiesel from microalgae. However, there are still a number of
      technological, market and policy barriers that are serious obstacles to the
      economic feasibility and competitiveness of such biofuels. Conversely, there are
      also a number of business opportunities if the production of such alternative
      biofuel becomes part of a larger integrated system following the Biorefinery
      strategy. In this case, other biofuels and chemical products of high added value
      are produced, contributing to an overall enhancement of the economic viability of
      the whole integrated system. Additionally, dual purpose microalgae-bacteria-based
      systems for treating wastewater and production of biofuels and chemical products
      significantly contribute to a substantial saving in the overall cost of
      microalgae biomass production. These types of systems could help to improve the
      competitiveness of biodiesel production from microalgae, according to some recent
      Life Cycle Analysis studies. Furthermore, they do not compete for fresh water
      resources for agricultural purposes and add value to treating the wastewater
      itself. This work reviews the most recent and relevant information about these
      types of dual purpose systems. Several aspects related to the treatment of
      municipal and animal wastewater with simultaneous recovery of microalgae with
      potential for biodiesel production are discussed. The use of pre-treated waste or
      anaerobic effluents from digested waste as nutrient additives for weak wastewater
      is reviewed. Isolation and screening of microalgae/cyanobacteria or their
      consortia from various wastewater streams, and studies related to population
      dynamics in mixed cultures, are highlighted as very relevant fields of research.
      The species selection may depend on various factors, such as the biomass and
      lipid productivity of each strain, the characteristics of the wastewater, the
      original habitat of the strain and the climatic conditions in the treatment
      plant, among others. Some alternative technologies aimed at harvesting biomass at
      a low cost, such as cell immobilization, biofilm formation, flocculation and bio
      flocculation, are also reviewed. Finally, a Biorefinery design is presented that
      integrates the treatment of municipal wastewater with the recovery of oleaginous
      microalgae, together with the use of seawater supplemented with anaerobically
      digested piggery waste for cultivating Arthrospira (Spirulina) and producing
      biogas, biodiesel, hydrogen and other high added value products. Such strategies
      offer new opportunities for the cost-effective and competitive production of
      biofuels along with valuable non-fuel products.

PMID- 22609183
TI  - Causality in administrative datasets.

PMID- 22609184
TI  - Usefulness of routine surveillance endomyocardial biopsy 6 months after heart
      transplantation.
AB  - BACKGROUND: Endomyocardial biopsy (EMB) remains the gold standard for detecting
      rejection episodes in orthotopic heart transplant (OTH) patients. Follow-up
      protocols vary widely between transplant centers. At our center, we have
      implemented a conservative strategy protocol and here we report our outcomes.
      METHODS: Patients from 2 cohorts were used for comparison analysis. OHT
      recipients from 1990 to 1995 comprised the standard strategy group, and those
      from 2004 to 2009 comprised the conservative strategy group. Survival outcomes
      and rejection episodes were compared between groups. RESULTS: Mean age at OHT was
      56 +/- 10 years in the standard strategy group and 53 +/- 10 years in the
      conservative strategy group. Both groups were predominantly composed of white
      men. The etiology of congestive heart failure was ischemic cardiomyopathy in more
      than 50% of the patients in both groups. From 6 to 12 months after OHT, we found
      that the number of episodes of rejection/total number of EMBs was 4.9% (8/163) in
      the standard group vs 2.0% (1/50) in the conservative group. From 12 to 24 months
      after transplant, the rate was 2.5% (8/320) in the standard group vs 11.9% (5/42)
      in the conservative group (p < 0.05). CONCLUSIONS: Surveillance EMB after 6
      months post-OHT in patients receiving contemporary immunosuppression is
      associated with a low yield of EMB-confirmed rejection in the absence of a
      clinical indication or echocardiographic findings that support clinical
      rejection. Most episodes of cellular rejection are mild and do not warrant
      treatment or a change in immunosuppression. The frequency of EMBs did not
      correlate with an increased risk of cardiac allograft vasculopathy or death.

PMID- 22609185
TI  - Recovery of right heart function with temporary right ventricular assist using a
      centrifugal pump in patients with severe biventricular failure.
AB  - BACKGROUND: Long-term outcomes of a biventricular assist device (BiVAD) support
      are worse than those of an isolated left ventricular assist device (LVAD)
      support. This study evaluated our strategy for right heart failure using a
      temporary right VAD (RVAD) with an extracorporeal centrifugal pump. METHODS: From
      January 2001 to December 2010, 108 patients underwent LVAD implantation at our
      institution and their clinical outcomes were studied. RESULTS: A temporary
      centrifugal RVAD was implanted in 26 patients. Multivariate logistic regression
      revealed pre-operative extracorporeal life support (odds ratio [OR], 37.0),
      central venous pressure (OR, 1.2), mean pulmonary artery pressure (OR, 0.9), and
      serum total bilirubin (OR, 1.4) were the risk factors for RVAD requirement. RVAD
      off test was conducted, and 11 of the 26 patients showed significant recovery of
      right heart function and were eventually removed from RVAD support. The survival
      of patients with isolated LVAD was significantly better than those with a
      paracorporeal pulsatile BiVAD (80% vs 11% at 1 year, p < 0.001). However, there
      was no significant difference between the survival of patients who underwent
      isolated LVAD support and those who were initially implanted with temporary BiVAD
      but underwent the RVAD removal (80% vs 73% at 1 year, p = 0.827). CONCLUSION: Our
      strategy with temporary RVAD for severe acute right heart failure was effective
      in selecting the patients who could be weaned from RVAD support. Patient survival
      was improved by avoiding the long-term support with a paracorporeal pulsatile
      BiVAD.

PMID- 22609186
TI  - Depletion of protein kinase N3 (PKN3) impairs actin and adherens junctions
      dynamics and attenuates endothelial cell activation.
AB  - Several pathways are involved in the control of endothelial cell morphology,
      endothelial permeability and function in order to maintain vascular homeostasis.
      Here we report that protein kinase N3 (PKN3) appears to play a pivotal role in
      maintaining endothelial cell morphology, cell-cell junctions and motility. An
      RNAi-based cell biological approach in cultured human endothelial cells (HUVEC)
      revealed that knockdown of PKN3 expression gave rise to cells with divergent cell
      morphology, impaired locomotion, disturbed adherens junctions (AJ) integrity and
      irregular actin organization. Notably, knockdown of PKN3 cells led to improper
      stress fiber formation and marked adhesiveness of intercellular adherens
      junctions when cells became stimulated with the pro-inflammatory cytokine TNF
      alpha. Moreover, TNF-alpha-induced ICAM-1 expression on the cell surface was
      reduced in cells with suppressed PKN3 expression. Finally, loss-of-function for
      PKN3 appeared to affect Pyk2 phosphorylation in endothelial cells. These
      observations suggest that PKN3 can be considered a novel protein implicated in
      remodeling the actin-adherens junction, possibly by linking ICAM-1-signaling with
      actin/AJ dynamics. We propose that loss of PKN3 function and concomitant
      aberrations in actin rearrangement may attenuate pro-inflammatory activation of
      endothelial cells.

PMID- 22609187
TI  - EXP-PAC: providing comparative analysis and storage of next generation gene
      expression data.
AB  - Microarrays and more recently RNA sequencing has led to an increase in available
      gene expression data. How to manage and store this data is becoming a key issue.
      In response we have developed EXP-PAC, a web based software package for storage,
      management and analysis of gene expression and sequence data. Unique to this
      package is SQL based querying of gene expression data sets, distributed
      normalization of raw gene expression data and analysis of gene expression data
      across experiments and species. This package has been populated with lactation
      data in the international milk genomic consortium web portal
      (http://milkgenomics.org/). Source code is also available which can be hosted on
      a Windows, Linux or Mac APACHE server connected to a private or public network
      (http://mamsap.it.deakin.edu.au/~pcc/Release/EXP_PAC.html).

PMID- 22609188
TI  - Formation and characterization of natural polysaccharide hollow nanocapsules via
      template layer-by-layer self-assembly.
AB  - With natural polysaccharides carrageenan (Car) and chitosan (Cs) as the polyanion
      and polycation, respectively, multilayer hollow nanocapsules have been fabricated
      via sequential layer-by-layer (LbL) electrostatic self-assembly from the
      sacrificed templates nanospheres (SiO(2)-NH(2)). The LbL assembly process with
      the polysaccharides on SiO(2)-NH(2) core was followed by zeta-potential and size
      analysis. The fabrication of (Car/Cs)(x) nanocapsules and the removing of the
      SiO(2)-NH(2) core templates were confirmed by TGA and EDS analysis. The
      morphology of SiO(2)(Car/Cs)(x) nanospheres and (Car/Cs)(x) nanocapsules were
      observed by TEM analysis. The size analysis of (Car/Cs)(x) nanocapsules indicated
      that the cyst wall thickness and cavity volume of the nanocapsules are pH and
      ionic strength dual responsive. Due to the biocompatibility of the natural
      polysaccharides carrageenan and chitosan and the responsiveness of nanocapsules
      to pH and ionic strength, the (Car/Cs)(x) multilayer nanocapsules are expected to
      be used as nanoreactors or nanocontainers to control the synthesis,
      encapsulation, and releasing behaviors of bioactive molecules.

PMID- 22609189
TI  - Adsorption of sugar surfactants at the air/water interface.
AB  - The adsorption isotherms of n-decyl-beta-D-glucoside (beta-C(10)G(1)) as well as
      various n-alkyl-beta-D-maltosides (beta-C(n)G(2)) with n=8, 10, 12 and 14 were
      determined from surface tension measurements. Based on the analysis of the
      adsorption isotherms, the total free energy change of adsorption was determined
      and a novel method was proposed to determine the maximum adsorbed amount of
      surfactant. It can be concluded that the driving force for adsorption first
      increases with increasing adsorbed amount of the sugar surfactants and then
      levels off in a plateau. This peculiar behaviour is interpreted as formation of a
      thin liquid-like alkane film of overlapping alkyl chains at the air/water
      interface once a certain adsorbed amount is exceeded. The driving force of
      adsorption depends on the alkyl chain length only and is not affected by the type
      of the head group. The hydrophobic contribution to the standard free energy
      change of adsorption was compared with the values of sodium alkylsulfate and
      alkyltrimethylammonium bromide surfactants. This comparison reveals that the
      hydrophobic driving force of adsorption is the largest for the sodium
      alkylsulfates, whereas it is the same for the sugar surfactants and the
      alkyltrimethylammonium bromides.

PMID- 22609190
TI  - Facile synthesis of highly dispersed palladium/polypyrrole nanocapsules for
      catalytic reduction of p-nitrophenol.
AB  - In this study, a facile one-step redox polymerization method for the preparation
      of highly dispersed palladium (Pd)/polypyrrole (PPy) nanocapsules has been
      demonstrated. During the polymerizaion process, the formation of RB-PdCl(4)(2-)
      complex via an electrostatic interaction plays a key role for the preparation of
      Pd/PPy composite nanocapsules. The well-dispersed Pd nanocrystals with small
      sizes of 2-4 nm embedded in PPy nanocapsules exhibited a good catalytic activity
      during the catalytic reduction of p-nitrophenol into p-aminophenol by NaBH(4) in
      aqueous solution. The kinetic apparent rate constant (k(app)) was about 8.87*10(
      3) s(-1). Moreover, the as-prepared Pd/PPy composite nanocapsules exhibited a
      good reusability, which could be repeatedly used for the reduction of p
      nitrophenol with a high catalytic activity for at least 10 successive cycles.

PMID- 22609191
TI  - Proteomic atlas of the human olfactory bulb.
AB  - The olfactory bulb (OB) is the first site for the processing of olfactory
      information in the brain and its deregulation is associated with
      neurodegenerative disorders. Although different efforts have been made to
      characterize the human brain proteome in depth, the protein composition of the
      human OB remains largely unexplored. We have performed a comprehensive analysis
      of the human OB proteome employing protein and peptide fractionation methods
      followed by LC-MS/MS, identifying 1529 protein species, corresponding to 1466
      unique proteins, which represents a 7-fold increase in proteome coverage with
      respect to previous OB proteome descriptions from translational models.
      Bioinformatic analyses revealed that protein components of the OB participated in
      a plethora of biological process highlighting hydrolase and phosphatase
      activities and nucleotide and RNA binding activities. Interestingly, 631 OB
      proteins identified were not previously described in protein datasets derived
      from large-scale Human Brain Proteome Project (HBPP) studies. In particular, a
      subset of these differential proteins was mainly involved in axon guidance,
      opioid signaling, neurotransmitter receptor binding, and synaptic plasticity.
      Taken together, these results increase our knowledge about the molecular
      composition of the human OB and may be useful to understand the molecular basis
      of the olfactory system and the etiology of its disorders.

PMID- 22609192
TI  - Plerixafor use in patients with previous mobilization failure: A multicenter
      experience.
AB  - Plerixafor in conjunction with G-CSF (G-P) is an effective strategy for
      hematopoietic stem cell mobilization in patients with previously failed
      mobilization attempt. Here we report our results with G-P among patients with at
      least one mobilization failure with G-CSF alone (G) or G-CSF plus chemotherapy (G
      C). The study included 20 consecutive patients with lymphoma and myeloma from
      five centers. In 14 (70%) patients, a minimum of 2*10(6)/kg CD34+ stem cells were
      collected and 16 out of 20 patients (80%) were able to proceed to ASCT. Our study
      indicates that plerixafor can safely rescue patients with a history of
      mobilization failure.

PMID- 22609193
TI  - Impact of age and diagnosis on viability during centrifugation and
      cryopreservation of peripheral blood stem cell products.
AB  - BACKGROUND: The viability of the hematopoietic stem cells infused to the patient
      is important for transplant outcome. STUDY DESIGN AND METHODS: We evaluated 31
      peripheral blood stem cell product collected from 15 patients. We aimed to check
      the viabilities of the cells from patients with different age and diagnosis, in
      different stages of the cryopreservation procedure. RESULTS: We showed a markedly
      decreased viability rate after centrifugation and addition of DMSO. Percentages
      of viabilities were similar between young and old patients in each step. Type of
      hematological malignancy did not make a significant influence on the viability.
      CONCLUSION: High speed centrifugation has a negative impact on the viability.

PMID- 22609194
TI  - Local effects and global impact in neurotoxicity and neurodegeneration: the Xi'an
      International Neurotoxicology Conference.

PMID- 22609195
TI  - The use of the Internet by people who die by suicide in England: a cross
      sectional study.
AB  - BACKGROUND: There is widespread concern regarding the possible influence of the
      Internet on suicidal behaviour. The aim of this study was to estimate the
      prevalence and characteristics of Internet-related suicide in England. METHODS:
      Cross sectional study based on detailed review of the inquest reports of suicides
      occurring in the areas served by 12 Coroners in England. Evidence of Internet use
      in relation to the suicide was sought for each death. RESULTS: Altogether inquest
      reports for 593 suicides (all methods) in 2005 and 166 suicides using specific
      methods in 2006-7 were assessed. There was evidence of a direct Internet
      contribution in nine (1.5% 95%CI 0.7 to 2.9%) of the 593 suicides in 2005. In
      seven (77.8%) of the cases the individuals had used the Internet to research the
      methods of suicide they used. Five (55.6%) individuals had used 'unusual' high
      lethality methods, whereas such methods were only used in 1.7% of all suicides
      (p<0.001). There was evidence of Internet involvement in 2.4% (0.7% to 6.1%) of
      the suicides in 2006-2007. None of the Internet-related suicides appeared to
      occur as part of a suicide pact. LIMITATIONS: The contribution of the Internet to
      suicide rates may be under-estimated in this analysis as Coroners are unlikely to
      comprehensively pursue the possibility of Internet involvement in all the deaths
      they investigate. CONCLUSIONS: Easy access to information about suicide methods
      and pro-suicide web sites on the Internet appears to contribute to a small but
      significant proportion of suicides. A key impact of the Internet appears to be in
      relation to information concerning suicide methods.

PMID- 22609196
TI  - Association of chronic hepatitis C with recurrent brief depression.
AB  - BACKGROUND: Depressive syndromes, including recurrent brief depression (RBD),
      have frequently been observed in association with chronic diseases characterized
      by immune activation, such as autoimmune thyroiditis or celiac disease. However,
      the association of RBD with chronic hepatitis C (CHC), a disease with an
      increased incidence of major depressive disorders, is unknown. METHODS:  CASES:
      135 (83 males, 52 females) consecutive treatment-naive patients with CHC.
      EXCLUSION CRITERIA: previous treatment with IFN-alpha, co-infection with
      hepatitis C virus (HCV) and hepatitis B virus, infection with human
      immunodeficiency virus (HIV), drug or alcohol abuse, or malignancy. CONTROLS: 540
      (332 males, 208 females) subjects without evidence of hepatitis, randomly
      extracted from the database of a previous epidemiological study. The psychiatric
      diagnosis was based on the Composite International Diagnostic Interview
      Simplified (CIDI-S), containing a specific section on RBD. RESULTS: A
      significantly higher rate of RBD was observed among both male and female patients
      with CHC (n=21, 15.5%) as compared to controls (n=34, 6.3%) (OR=2.6, CI 95% from
      1.37 to 4.93). CONCLUSION: The present study provides the first evidence of an
      association between CHC and RBD, independent of treatment with IFN-alpha and not
      influenced by substance or alcohol abuse. The results are similar to those found
      in other conditions with immune activation. RBD may be another expression of mood
      disorders in such conditions.

PMID- 22609197
TI  - Do parents know best? Parent-reported vs. child-reported depression symptoms as
      predictors of future child mood disorder in a high-risk sample.
AB  - BACKGROUND: Parents with depression are thought to be unreliable reporters of
      children's depression symptoms, but findings are contradictory and primarily
      focus on discrepancies between parent and child reports rather than on the
      predictive validity of informants. Using a sample of parents with recurrent
      depression, our analyses utilised data from a prospective high-risk longitudinal
      study (the Early Prediction of Adolescent Depression study) to investigate
      whether baseline parental reports of child depression symptoms predicted new
      onset mood disorder (NOMD) in children. METHODS: The sample included 287 parents
      with a history of recurrent depression and their adolescent offspring (aged 9-17
      at baseline). Families were assessed at three time points. The Child and
      Adolescent Psychiatric assessment (parent and child versions) was used to assess
      the number of child depression symptoms (computed separately by informant at
      baseline) and NOMD at follow-up. All DSM-IV diagnoses were confirmed by two child
      psychiatrists. RESULTS: Parent reports of child depression symptoms at baseline
      significantly predicted NOMD in children. Secondary analyses stratifying the
      sample according to child age showed that, for younger children, parent reports
      were significantly better at predicting NOMD compared to child reports. For
      children aged 12 or older, there were no significant differences between parent
      and child reports in predicting NOMD. The pattern of association remained the
      same once we controlled for baseline levels of parental depression. LIMITATIONS:
      Not all parents were currently experiencing an episode of depression at the
      baseline assessments; the sample consisted predominantly of mothers, thus
      findings may not be applicable to fathers or families without a history of
      parental depression. CONCLUSIONS: In this high risk sample, child and parent
      ratings of depression predict new onset child mood disorder to a similar degree.
      Clinicians and researchers should give due consideration to parent ratings of
      their children's depression symptoms, regardless of whether the parent suffers
      with depression.

PMID- 22609198
TI  - Rnf11-like is a novel component of NF-kappaB signaling, governing the posterior
      patterning in the zebrafish embryos.
AB  - RING finger protein 11 (RNF11) is a novel regulator of immunity and cell survival
      via ubiquitination process in mammalian cells whereas its vertebrate embryonic
      roles are undefined. Here, we are reporting the isolation, expression and
      functional roles of an RNF11 orthologue, Rnf11-like in zebrafish embryos.
      Zebrafish Rnf11-like is composed of 154 amino acids containing RING-H2-finger
      domain in the C-terminal region and PY-motif. Spatiotemporal expression patterns
      of rnf11-like indicate that rnf11-like is expressed maternally and zygotically
      throughout embryogenesis. However, rnf11-like transcripts are present
      specifically in the presomatic mesoderm (PSM), and later in the brain and retina.
      Knock-down of Rnf11-like using rnf11-like-specific morpholino causes cell death
      and developmental defects in the posterior somites, elevating transcripts of NF
      kappaB target gene, ikk1, a negative regulator of NF-kappaB signaling. All these
      findings indicate that Rnf11-like is an essential component of NF-kappaB
      signaling pathway for specification of the posterior somites in zebrafish
      embryos.

PMID- 22609199
TI  - The enhancer of zeste homolog 2 (EZH2), a potential therapeutic target, is
      regulated by miR-101 in renal cancer cells.
AB  - We investigated a prognostic significance and the mechanism of aberrant nuclear
      expression of EZH2, a histone methyltransferase, in human renal cell carcinoma
      (RCC). We found nuclear EZH2 in 48 of 100 RCCs and it was significantly
      correlated with worse survival in RCC patients. We detected a decreased
      expression of miR-101 in 15 of 54 RCCs. We found that re-expression of miR-101
      resulted in EZH2 depletion and decreased renal cancer cell proliferation. Our
      results show nuclear EZH2 as a prognostic marker of worse survival in human RCC,
      and identify miR-101 as a negative regulator of EZH2 expression and renal cancer
      cell proliferation.

PMID- 22609200
TI  - Surf4 modulates STIM1-dependent calcium entry.
AB  - Store-operated Ca(2+) entry (SOCE) is crucial for various physiological responses
      in immune cells. Although it is known that STIM1 relocates into discrete puncta
      juxtaposed to the plasma membrane to initiate SOCE, the machinery modulating the
      function of STIM1 remains unclear. We explored to find its modulators using
      affinity purification for STIM1-binding proteins and identified surfeit locus
      protein 4 (Surf4). Surf4 associated with STIM1 in the endoplasmic reticulum.
      Deletion of Surf4 in DT40 B cells resulted in marked increase of SOCE and
      facilitation of STIM1 clustering upon store-depletion. These findings suggest the
      modulatory function of Surf4 for STIM1-mediated SOCE.

PMID- 22609201
TI  - A simple strand-specific RNA-Seq library preparation protocol combining the
      Illumina TruSeq RNA and the dUTP methods.
AB  - Preserving the original RNA orientation information in RNA-Sequencing (RNA-Seq)
      experiment is essential to the analysis and understanding of the complexity of
      mammalian transcriptomes. We describe herein a simple, robust, and time-effective
      protocol for generating strand-specific RNA-seq libraries suited for the Illumina
      sequencing platform. We modified the Illumina TruSeq RNA sample preparation by
      implementing the strand specificity feature using the dUTP method. This protocol
      uses low amounts of starting material and allows a fast processing within two
      days. It can be easily implemented and requires only few additional reagents to
      the original Illumina kit.

PMID- 22609202
TI  - Endoplasmic reticulum stress and the on site function of resident PTP1B.
AB  - Growing evidence links the stress at the endoplasmic reticulum (ER) to
      pathologies such as diabetes mellitus, obesity, liver, heart, renal and
      neurodegenerative diseases, endothelial dysfunction, atherosclerosis, and cancer.
      Therefore, identification of molecular pathways beyond ER stress and their
      appropriate modulation might alleviate the stress, and direct toward novel tools
      to fight this disturbance. An interesting resident of the ER membrane is protein
      tyrosine phosphatase 1B (PTP1B), an enzyme that negatively regulates insulin and
      leptin signaling, contributing to insulin and leptin resistance. Recently, new
      functions of PTP1B have been established linked to ER stress response. This
      review evaluates the novel data on ER stressors, discusses the mechanisms beyond
      PTP1B function in the ER stress response, and emphasizes the potential
      therapeutic exploitation of PTP1B to relieve ER stress.

PMID- 22609203
TI  - Tandem zyxin LIM sequences do not enhance force sensitive accumulation.
AB  - The ability to sense mechanical forces is vital to cell physiology. Yet, the
      molecular basis of mechano-signaling remains unclear. Previous studies have shown
      that zyxin, a focal adhesion protein, is recruited at force-bearing sites on the
      actin cytoskeleton and, therefore, identifying zyxin as a mechano-sensing protein
      candidate. Furthermore, zyxin accumulation at force-bearing sites requires the
      LIM domain located at the C-terminus of zyxin. The zyxin LIM domain consists of
      three LIM motifs, each containing two zinc-binding sites. Since individual LIM
      motifs do not accumulate at focal adhesions or force-bearing sites, we
      hypothesize that multiple zyxin LIM domains increase force sensitivity. Using a
      miniature force sensor and GFP-tagged LIM variants, we quantified the
      relationship between single, tandem dimer and trimer LIM protein localization and
      traction forces. While the presence of extra LIM domains affected VASP
      recruitment to focal adhesions, force sensitivity was not enhanced over the
      single LIM domain. Therefore, zyxin force sensitivity is optimal with a single
      LIM domain, while additional LIM domains fail to enhance force sensitivity.

PMID- 22609204
TI  - Wnt5a signaling is a substantial constituent in bone morphogenetic protein-2
      mediated osteoblastogenesis.
AB  - Wnts are secreted glycoproteins that mediate developmental and post-developmental
      physiology by regulating cellular processes including proliferation,
      differentiation, and apoptosis through beta-catenin-dependent canonical and beta
      catenin-independent noncanonical pathway. It has been reported that Wnt5a
      activates noncanonical Wnt signaling through receptor tyrosine kinase-like orphan
      receptor 2 (Ror2). Although it appears that Wnt5a/Ror2 signaling supports normal
      bone physiology, the biological significance of noncanonical Wnts in osteogenesis
      is essentially unknown. In this study, we identified expression of Wnt5a in
      osteoblasts in the ossification zone of the tibial growth plate as well as bone
      marrow of the rat tibia as assessed by immunohistochemistry. In addition, we show
      that osteoblastic differentiation mediated by BMP-2 is associated with increased
      expression of Wnt5a and Ror2 using cultured pre-osteoblasts, MC3T3-E1 cells.
      Silencing gene expression of Wnt5a and Ror2 in MC3T3-E1 cells results in
      suppression of BMP-2-mediated osteoblastic differentiation, suggesting that Wnt5a
      and Ror2 signaling are of substantial importance for BMP-2-mediated osteoblastic
      differentiation. BMP-2 stimulation induced phosphorylation of Smad1/5/8 in a
      similar fashion in both siWnt5a-treated cells and control cells, suggesting that
      Wnt5a was dispensable for the phosphorylation of Smads by BMP-2. Taken together,
      our results suggest that Wnt5a/Ror2 signaling appears to be involved in BMP-2
      mediated osteoblast differentiation in a Smad independent pathway.

PMID- 22609205
TI  - Blockade of beta-cell K(ATP) channels by the endocannabinoid, 2
      arachidonoylglycerol.
AB  - The endocannabinoid system has been demonstrated to be active in the pancreatic
      beta-cell. However the effects of the endocannabinoids (ECs) on insulin secretion
      are not well defined and may vary depending on the metabolic state of the beta
      cell. Specifically it is not known whether the effects of the ECs occur by
      activation of the cannabinoid receptors or via their direct interaction with the
      ion channels of the beta-cell. To begin to delineate the effects of ECs on beta
      cell function, we examined how the EC, 2-AG influences beta-cell ion channels in
      the absence of glucose stimulation. The mouse insulinoma cell line R7T1 was used
      to survey the effects of 2-AG on the high voltage activated (HVA) calcium, the
      delayed rectifier (K(v)), and the ATP-sensitive K (K(ATP)) channels by whole cell
      patch clamp recording. At 2mM glucose, 2-AG inhibited the HVA calcium (the
      majority of which are L-type channels), K(v), and K(ATP) channels. The channel
      exhibiting the most sensitivity to 2-AG blockade was the K(ATP) channel, where
      the IC(50) for 2-AG was 1 MUM. Pharmacological agents revealed that the blockade
      of all these channels was independent of cannabinoid receptors. Our results
      provide a mechanism for the previous observations that CB1R agonists increase
      insulin secretion at low glucose concentrations through CB1R independent blockade
      of the K(ATP) channel.

PMID- 22609206
TI  - Impairment of the extrusion transporter for asymmetric dimethyl-L-arginine: a
      novel mechanism underlying vasospastic angina.
AB  - A 37-year old male patient presented with frequent angina attacks (up to 40/day)
      largely resistant to classical vasodilator therapy. The patient showed severe
      coronary and peripheral endothelial dysfunction, increased platelet aggregation
      and increased platelet-derived superoxide production. The endothelial nitric
      oxide synthase (eNOS)-inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME)
      reduced superoxide formation in platelets identifying "uncoupled" eNOS as a
      superoxide source. Oral L-arginine normalized coronary and peripheral endothelial
      dysfunction and reduced platelet aggregation and eNOS-derived superoxide
      production. Plasma concentrations of the endogenous NOS inhibitor asymmetric
      dimethyl-L-arginine (ADMA), representing an independent risk factor for
      cardiovascular disease, were normal in the patient. However, immediately after
      oral administration of cationic amino acid (CAA), plasma ADMA levels rose
      markedly, demonstrating increased ADMA efflux from intracellular stores. ADMA
      efflux from mononuclear cells of the patient was accelerated by CAA, but not
      neutral amino acids (NAA) demonstrating impairment of y(+)LAT (whose expression
      was found reduced in these cells). These data suggest that impairment of y(+)LAT
      may cause intracellular (endothelial) ADMA accumulation leading to systemic
      endothelial dysfunction. This may represent a novel mechanism underlying
      vasospastic angina and vascular dysfunction in general. Moreover, these new
      findings contribute to the understanding of the l-arginine paradox, the
      improvement of eNOS activity by oral L-arginine despite sufficient cellular l
      arginine levels to ensure proper function of this enzyme.

PMID- 22609207
TI  - Regulation of the alternative splicing of sarcoplasmic reticulum Ca2+-ATPase1
      (SERCA1) by phorbol 12-myristate 13-acetate (PMA) via a PKC pathway.
AB  - Myotonic dystrophy type 1 (DM1) is a multi-systemic disease with no established
      treatment to date. Small, cell-permeable molecules hold the potential to treat
      DM1. In this study, we investigated the association between protein kinase C
      (PKC) signaling and splicing of sarcoplasmic reticulum Ca(2+)-ATPase1 (SERCA1).
      Our aim was to clarify the mechanisms underlying the regulation of alternative
      splicing, in order to explore new therapeutic strategies for DM1. By assessing
      the splicing pattern of the endogenous SERCA1 gene in HEK293 cells, we found that
      treatment with phorbol 12-myristate 13-acetate (PMA) regulated SERCA1 splicing.
      Interestingly, treatment with PMA for 48 h normalized SERCA1 splicing, while
      treatment for 1.5h promoted aberrant splicing. These two responses showed dose
      dependency and were completely abolished by the PKC inhibitor Ro 31-8220.
      Furthermore, repression of PKCbetaII and PKCtheta by RNAi mimicked prolonged PMA
      treatment. These results indicate that PKC signaling is involved in the splicing
      of SERCA1 and provide new evidence for a link between alternative splicing and
      PKC signaling.

PMID- 22609208
TI  - Improved viability and activity of neutrophils differentiated from HL-60 cells by
      co-culture with adipose tissue-derived mesenchymal stem cells.
AB  - Neutropenia is a principal complication of cancer treatment. We investigated the
      supportive effect of adipose tissue-derived mesenchymal stem cells (AD-MSCs) on
      the viability and function of neutrophils. Neutrophils were derived from HL-60
      cells by dimethylformamide stimulation and cultured with or without AD-MSCs under
      serum-starved conditions to evaluate neutrophil survival, proliferation, and
      function. Serum starvation resulted in the apoptosis of neutrophils and decreased
      cell survival. The co-culture of neutrophils and AD-MSCs resulted in cell
      survival and inhibited neutrophil apoptosis under serum-starved conditions. The
      survival rate of neutrophils was prolonged up to 72 h, and the expression levels
      of interferon (IFN)-alpha, granulocyte colony-stimulating factor (G-CSF),
      granulocyte-macrophage colony-stimulating factor, and transforming growth factor
      (TGF)-beta in AD-MSCs were increased after co-culture with neutrophils. AD-MSCs
      promoted the viability of neutrophils by inhibiting apoptosis as well as
      enhancing respiratory burst, which could potentially be mediated by the increased
      expression of IFN-alpha, G-CSF, and TGF-beta. Thus, we conclude that the use of
      AD-MSCs may be a promising cell-based therapy for increasing immunity by
      accelerating neutrophil function.

PMID- 22609209
TI  - Conjugated linoleic acid supplementation caused reduction of perilipin1 and
      aberrant lipolysis in epididymal adipose tissue.
AB  - Perilipin1, a coat protein of lipid droplet, plays a key role in adipocyte
      lipolysis and fat formation of adipose tissues. However, it is not clear how the
      expression of perilipin1 is affected in the decreased white adipose tissues (WAT)
      of mice treated with dietary supplement of conjugated linoleic acids (CLA). Here
      we obtained lipodystrophic mice by dietary administration of CLA which exhibited
      reduced epididymal (EPI) WAT, aberrant adipocytes and decreased expression of
      leptin in this tissue. We found both transcription and translation of perilipin1
      was suppressed significantly in EPI WAT of CLA-treated mice compared to that of
      control mice. The gene expression of negative regulator tumor necrosis factor
      alpha (TNFalpha) and the positive regulator Peroxisome Proliferator-Activated
      Receptor-gamma (PPARgamma) of perilipin1 was up-regulated and down-regulated,
      respectively. In cultured 3T3-L1 cells the promoter activity of perilipin1 was
      dramatically inhibited in the presence of CLA. Using ex vivo experiment we found
      that the basal lipolysis was elevated but the hormone-stimulated lipolysis
      blunted in adipose explants of CLA-treated mice compared to that of control mice,
      suggesting that the reduction of perilipin1 in white adipose tissues may at least
      in part contribute to CLA-mediated alternation of lipolysis of WAT.

PMID- 22609210
TI  - Inhibition of increased indoleamine 2,3-dioxygenase activity attenuates
      Toxoplasma gondii replication in the lung during acute infection.
AB  - The regulation of local L-tryptophan concentrations by tryptophan-degrading
      enzyme, indoleamine 2,3-dioxygenase (IDO) induced by various stimuli such as
      interferon-gamma (IFN-gamma) is one of the key mechanisms in antimicrobial
      effect. Recently, IDO is also focused on an immunosuppressive mechanism shared by
      several different immune cell types. Here, we show that inhibition of increased
      IDO activity maybe involved in the antiparasitic mechanism during Toxoplasma
      gondii (T. gondii) infection in vivo. In this study, we investigated the role of
      IDO by using IDO-gene-deficient (IDO KO) mice and by administering a competitive
      enzyme inhibitor, 1-methyl-D,L-tryptophan (1MT), to wild-type mice following T.
      gondii infection. Although depletion of lung l-tryptophan did not occur in IDO KO
      mice after T. gondii infection, the increased mRNA expression of T. gondii
      surface antigen gene 2 (SAG2) and the inflammatory cytokines in the lung were
      drastically reduced in the IDO KO mice following infection. We also found that
      complete depletion of lung l-tryptophan was observed in wild-type mice after
      infection, but not in mice treated with 1MT. At the same time, 1MT suppressed the
      increased mRNA expression of SAG2. Taken together, we observed that the
      inflammatory damage was significantly decreased by the administration of 1MT in
      the lung after infection. Inhibition of the IDO activity or the elimination of
      IDO's substrate may be an effective therapy against microbial diseases.

PMID- 22609211
TI  - Lack of association of -251T/A polymorphism in interleukin 8 gene with
      susceptibility to obsessive-compulsive disorder in Chinese Han population.

PMID- 22609212
TI  - Genetic polymorphisms within tumor necrosis factor gene promoter region: a role
      for susceptibility to ventilator-associated pneumonia.
AB  - Debatable findings exist among various studies regarding the impact of single
      nucleotide polymorphisms (SNPs) within the promoter region of the tumor necrosis
      factor (TNF) gene for susceptibility to infections. Their impact was investigated
      in a cohort of mechanically ventilated patients who developed ventilator
      associated pneumonia (VAP). Two-hundred and thirteen mechanically ventilated
      patients who developed VAP were enrolled. Genomic DNA was extracted and SNPs at
      the -376, -308 and -238 position of the promoter region of the TNF gene were
      assessed by restriction fragment length polymorphisms. Monocytes were isolated
      from 47 patients when they developed sepsis and stimulated by bacterial endotoxin
      for the production of TNFalpha and of interleukin-6 (IL-6). Patients were divided
      into two groups; 166 patients bearing only wild-type alleles of all three studied
      polymorphisms; and 47 patients carrying at least one A allele of the three
      studied SNPs. Time between start of mechanical ventilation and advent of VAP was
      significantly shorter in the second group than in the first group (log-rank:
      4.416, p: 0.041). When VAP supervened, disease severity did not differ between
      groups. Stimulation of TNFalpha and of IL-6 was much greater by monocytes for
      patients carrying A alleles. Carriage of at least one A allele of the three
      studied SNPs at the promoter region of the TNF-gene is associated with shorter
      time to development of VAP but it is not associated with disease severity.
      Findings may be related with a role of the studied SNPs in the production of pro
      inflammatory cytokines.

PMID- 22609213
TI  - Genetically determined inflammatory-response related cytokine and chemokine
      transcript profiles between mammary carcinoma resistant and susceptible rat
      strains.
AB  - Multiple human breast and rat mammary carcinoma susceptibility (Mcs) alleles have
      been identified. Wistar Kyoto (WKY) rats are resistant to developing mammary
      carcinomas, while Wistar Furth (WF) females are susceptible. Gene transcripts at
      Mcs5a1, Mcs5a2, and Mcs5c are differentially expressed between resistant WKY and
      susceptible WF alleles in immune-system tissues. We hypothesized that immune
      related gene transcript profiles are genetically determined in mammary carcinoma
      resistant and susceptible mammary glands. Low-density QPCR arrays were used to
      compare inflammation related genes between mammary carcinoma resistant WKY and
      susceptible WF females. Mammary gland gene transcript levels predicted to be
      different based on arrays were tested in independent samples. In total, 20
      females per strain were exposed to 7,12-dimethylbenz(a)anthracene (DMBA) to
      induce mammary carcinogenesis. Twelve age-matched controls per strain without
      DMBA were included to determine main effects of DMBA-exposure. Significant (ANOVA
      P <= 0.01) effects of strain on mammary gland transcript level were observed for
      Cx3cl1, Il11ra, Il4, C3, Ccl20, Ccl11, Itgb2, Cxcl12, and Cxcr7. Significant
      effects of DMBA-exposure were observed for Cx3cl1, Il11ra, Cxcr4, Il4ra, and Il4.
      Strain and DMBA-exposure interaction effects were significant for Cx3cl1.
      Transcript levels of Cxcr7 relative to Cxcr4 were modified differently by DMBA in
      mammary carcinoma resistant and susceptible strains. In conclusion, several
      genetically-determined differences in cytokine, chemokine, and receptor gene
      transcript levels were identified between mammary carcinoma susceptible and
      resistant mammary glands, which may be indicative of cell populations and
      activities that suppress mammary carcinogenesis in resistant genotypes.

PMID- 22609214
TI  - Predictive value of the CHA2DS2-VASc score in atrial fibrillation patients at
      high risk for stroke despite oral anticoagulation.
AB  - INTRODUCTION AND OBJECTIVES: The risk of stroke in atrial fibrillation is
      heterogeneous and depends upon underlying clinical conditions included in current
      risk stratification schemes. Recently, the CHA(2)DS(2)-VASc score has been
      included in guidelines to be more inclusive of common stroke risk factors seen in
      everyday clinical practice, and useful in defining "truly low risk" subjects. We
      aimed to assess the usefulness of CHA(2)DS(2)-VASc score to give us an additional
      prognostic perspective for adverse events and mortality among "real world"
      anticoagulated patients with atrial fibrillation who are often elderly with many
      comorbidities. METHODS: Consecutive outpatients with permanent/paroxysmal
      nonvalvular atrial fibrillation with CHA(2)DS(2)-VASc>=2 and stabilized oral
      anticoagulation (international normalized ratio 2.0-3.0) for at least the
      preceding 6 months were recruited. Patients with CHA(2)DS(2)-VASc>=2 were
      selected. Adverse cardiovascular events including stroke, acute coronary
      syndrome, or heart failure; major bleeds; and mortality were recorded during more
      than 2.5-year-follow-up. RESULTS: Of 933 patients (93.5%) assessed, 432 were
      males, median age 76 (71-81) years. After a follow-up of 946 (782-1068) days, 109
      patients (11.7%) had adverse cardiovascular events, 80 patients (8.6%) had major
      bleeds, 101 patients (10.8%) died, and 230 (24.6%) had major adverse events
      (composite end-point). Increasing CHA(2)DS(2)-VASc score by 1 point had a
      significant impact on the occurrence of cardiovascular events (hazard ratio=1.27;
      95% confidence interval, 1.13-1.44; P<.001), mortality (hazard ratio=1.36; 95%
      confidence interval, 1.19-1.54; P<.001); and major adverse events (hazard
      ratio=1.23; 95% confidence interval, 1.13-1.34; P<.001). CHA(2)DS(2)-VASc score
      was not associated with major bleeding episodes. CONCLUSIONS: Among high risk
      atrial fibrillation patients on oral anticoagulation, CHA(2)DS(2)-VASc
      successfully predicts cardiovascular events and mortality, but not major bleeds.

PMID- 22609216
TI  - Relationship among metabolic syndrome, C358A polymorphism of the endocannabinoid
      degrading enzyme fatty acid amide hydrolase (FAAH) and insulin resistance.
AB  - BACKGROUND: It has been demonstrated that the polymorphism 385 C/A of FAAH (fatty
      acid amide hydrolase) was associated with obesity and metabolic disorders.
      OBJECTIVE: The aim of our study was to investigate the relationship of the
      polymorphism (cDNA 385 C->A) of FAAH gene and insulin resistance in obese
      patients with and without metabolic syndrome. DESIGN: A population of 799 obese
      patients was analyzed in cross-sectional survey. A bioimpedance, blood pressure,
      serial assessment of nutritional intake with 3 days written food records and
      biochemical analysis were performed. Genotype of FAAH gene polymorphism was
      studied. RESULTS: Prevalence of metabolic syndrome (MS) with ATP III definition
      was 49.8% (398 patients) and 50.2% patients without MS (n=401 patients).
      Prevalence of FAAH genotypes was similar in patients with metabolic syndrome
      (69.6% wild genotype and 30.4% mutant genotype) and without metabolic syndrome
      (66.6% wild genotype and 33.4% mutant genotype). In patients without metabolic
      syndrome, insulin and HOMA levels were higher in mutant genotype than wild type
      group. CONCLUSION: The main finding is the lack of association of the FAAH
      genotypes with metabolic syndrome prevalence. Patients with mutant genotype group
      of FAAH gene and without metabolic syndrome have higher insulin and HOMA levels
      than wild type group.

PMID- 22609217
TI  - The effects of Pilates on metabolic control and physical performance in
      adolescents with type 1 diabetes mellitus.
AB  - Physical activity is a substantial method in the management of children and
      adolescents with Type 1 diabetes mellitus but it is not considered as a treatment
      for diabetes. The aim of this study was to investigate the effects of Pilates
      exercises on metabolic control and physical performance in patients with type 1
      diabetes mellitus. Thirty one sedentary patients with type 1 diabetes mellitus,
      ranging in age from 12 to 17 (experimental group, n=17 and control group, n=14)
      were submitted to 12 weeks of Pilates training. Participants underwent tests to
      determine the physical performance and metabolic control before and after 12
      weeks of Pilates session. At the end of study, there were significant alterations
      in physical performance of the study group. Peak power, mean power, vertical jump
      and flexibility of study group increased. There were no alterations for this
      parameters in the control group. There was no significant difference for glycated
      hemoglobin (HbA1c) in both groups. CONCLUSIONS: Physical performance increased
      via Pilates exercises in the patients with type 1 DM. However there were no
      changes in metabolic control. In the present study, the positive effects of
      exercise on metabolic control could not be shown in patients with Type 1 DM.

PMID- 22609218
TI  - Osmotic stress induced oxidative damage: possible mechanism of cataract formation
      in diabetes.
AB  - Chronic hyperglycemia causes increased level of reactive oxygen species which is
      thought to be involved in the pathogenesis of diabetes associated complications
      including cataract. In diabetic cataractous lens, over production of free
      radicals and decreased capacity of antioxidant defense system are the major
      contributors to oxidative damage by polyol pathway and advanced glycation end
      products. The current study focused on analysis of factors associated with
      osmotic imbalance and oxidative stress in aging and diabetic human cataractous
      lenses. We examined activities of polyol pathway enzymes, G6PD and glutathione
      system in lenses from subjects suffering from cataract due to aging and diabetes.
      We observed elevated activities of aldose reductase and sorbitol dehydrogenase
      while G6PD and glutathione system enzyme activities were found to be lower in
      cataractous subjects suffering from diabetes. The findings from the current study
      support the premise that osmotic imbalance, AGEs formation and oxidative stress
      contribute synergistically to the development of lens opacity in hyperglycemia.

PMID- 22609220
TI  - Treatment of pustular psoriasis: from the Medical Board of the National Psoriasis
      Foundation.
AB  - BACKGROUND: A task force of the National Psoriasis Foundation Medical Board was
      convened to evaluate treatment options for pustular psoriasis. Meetings were held
      by teleconference. Consensus on treatment of pustular psoriasis was achieved.
      Pustular psoriasis has been classified into localized and generalized forms.
      There are a number of treatment modalities, but there is little evidence-based
      information to guide the management of this type of psoriasis. OBJECTIVES: The
      purpose of this article was to present treatment recommendations to aid in the
      treatment of patients with pustular psoriasis. METHODS: A literature review was
      conducted to examine treatment options for pustular psoriasis and assess the
      strength of the literature for each option. RESULTS: Overall the quality of the
      literature about the treatment of pustular psoriasis is weak. Treatment should be
      governed by the extent of involvement and severity of disease. Acitretin,
      cyclosporine, methotrexate, and infliximab are considered to be first-line
      therapies for those with generalized pustular psoriasis. Adalimumab, etanercept,
      and psoralen plus ultraviolet A are second-line modalities in this setting.
      Pustular psoriasis in children, in pregnant women, and in localized forms alter
      which agents are first-line modalities as concerns such as teratogenicity need to
      be factored into the decisionmaking for the individual patient. LIMITATIONS:
      There are few high-quality studies examining treatment options for pustular
      psoriasis. CONCLUSIONS: Treatment of patients with pustular psoriasis depends on
      the severity of presentation and patient's underlying risk factors. The data are
      extremely limited for this type of psoriasis and we encourage further
      exploration.

PMID- 22609219
TI  - Diverse cutaneous side effects associated with BRAF inhibitor therapy: a
      clinicopathologic study.
AB  - BACKGROUND: Vemurafenib, a novel selective small molecule inhibitor of BRAF, has
      recently been shown to be effective in the treatment of melanomas harboring the
      BRAF V600E mutation. Similar to the broad-spectrum RAF inhibitor sorafenib,
      vemurafenib induces development of squamous cell carcinomas and keratoacanthomas
      as a side effect of therapy. OBJECTIVE: We sought to detail additional cutaneous
      adverse effects of vemurafenib and a similar BRAF inhibitor, dabrafenib. METHODS:
      We evaluated the clinical and histologic feature of skin side effects developing
      on vemurafenib or dabrafenib therapy in 14 patients. RESULTS: Eight patients
      developed one or more squamous cell carcinomas, and 11 patients formed benign
      verrucous keratoses. Eight patients developed single lesions and/or widespread
      eruptions with histopathologic findings of acantholytic dyskeratosis, consistent
      with warty dyskeratomas and Darier- or Grover-like rashes, respectively. One
      patient developed palmoplantar hyperkeratosis, and darkening of existing nevi and
      new nevi within 2 months of starting vemurafenib. Side effects presented as early
      as 1 week after beginning therapy, with a mean time of onset of 12.6 weeks in our
      cohort. LIMITATIONS: This study was limited by the small number of cases, all
      from a single institution. CONCLUSION: Selective BRAF inhibitor therapy is
      associated with the development of malignant and benign growths, including
      keratoacanthoma-like squamous cell carcinomas, warty dyskeratomas, and verrucous
      keratoses, along with widespread eruptions with histologic features of
      acantholytic dyskeratosis. Given the potential for malignant lesions to develop
      on treatment, awareness of potential adverse effects of these agents is
      necessary, and a low threshold for biopsy of new growths is recommended.

PMID- 22609221
TI  - Difference in the thickness of mouthguards fabricated from step-type polyolefin
      polystyrene copolymer sheets differently arranged v-shaped grooves.
AB  - PURPOSE: The aim of this study was to evaluate the change in thickness of
      different types of step-type mouthguard sheets after suction molding in response
      to heating conditions for more effective use. METHODS: Four types of mouthguard
      sheets (Impact Guard((r))) were compared: a step-type sheet; a step-type sheet
      with a v-shaped groove 30 mm from the anterior end; a step-type sheet with a v
      shaped groove at the inferior margin of the step portion; and a step-type sheet
      with a v-shaped groove at the center of the step portion. The working model was
      trimmed to a height of 20-mm at the incisor and 15-mm at the first molar. The
      thickness of sheet was measured at points defined on the incisor and molar
      portion. The heating condition was defined when the sheet sagged by 15-mm below
      the level of the clamp. Differences in the percent change in thickness from types
      of sheets were analyzed using Scheffe's multiple comparison test. Additionally,
      the sheet type of thickness change with smallest was compared between the 15-mm
      and 20-mm sheet-sagging condition by paired t-test. RESULTS: The sheet with a v
      shaped groove at the center of the step portion showed smallest reduction in
      thickness. With this type of sheet, no significant difference in thickness was
      observed under heating conditions. CONCLUSIONS: The present results demonstrate
      the thickness of the incisor and molar portions of a step-type mouthguard sheet
      can be maintained by creating a v-shaped groove at the center of the step
      portion, regardless of heating condition.

PMID- 22609222
TI  - Characterization of two Ni-Cr dental alloys and the influence of casting mode on
      mechanical properties.
AB  - PURPOSE: The aim of this study was to evaluate the tensile strength, elongation,
      microhardness (MHV), composition and microstructure of two Ni-Cr based alloy,
      cast under different casting conditions. METHODS: Before casting, the alloy
      ingots were evaluated as regards composition (EDX) and microstructure (Optical
      microscopy, SEM and EDX). The casting conditions were as follows: electromagnetic
      induction in an environment controlled with argon (EWA), electromagnetic
      induction in an environment under vacuum (EWV), electromagnetic induction without
      atmosphere control (EWNC) and blowtorch (BT). For each condition, 16 specimens
      were obtained, each measuring 25 mm high and 2.5mm in diameter. The ultimate
      tensile strength (UTS) and elongation (EL) tests were performed in a Kratos
      machine (1.0mm/min). Fractured specimens were embedded in bakelite resin and
      polished for Vickers Microhardness analysis (1000 g/10s) with 4 penetrations in
      each specimen. The UTS, EL and MHV results were evaluated for two-way ANOVA and
      Tukey's test (alpha=0.05). RESULTS: The cross-product interaction was
      statistically significant for all properties evaluated (p<0.0001), lower UTS, VHN
      and high elongation means were observed for the Ni-Cr-Mo-Be alloy tested when
      cast under the induction/argon (p<0.05). Higher UTS means were found for Ni-Cr-Mo
      Ti alloy tested when cast under the induction/vacuum, and induction/air and
      flame/air condition (p<0.05). The two alloys show a microstructure with a
      dendritic formation with the presence of eutectic presence. CONCLUSION: The Ni-Cr
      Mo-Ti alloy showed high UTS, MHV and lowest EL comparaded with the tradicional Ni
      Cr-Mo-Be, that show lowest UTS, MHV and higher EL when cast on induction/argon.

PMID- 22609223
TI  - Fabrication of fixed implant prostheses using function bite impression technique
      (FBI technique).
AB  - PATIENT: The patient was partially edentulous, lacking both the first mandibular
      molars. The FBI and the conventional impression technique were used for the
      fabrication of implant-fixed prosthesis replacing the right and left molars,
      respectively. In the FBI technique, the definitive impression was made under
      occlusal force and functionally generated path (FGP) recording at the same time.
      The right and left occlusal contact areas were compared after completing the
      implant-fixed prosthesis rehabilitation. DISCUSSION: It has been suggested that
      accuracy of the impression and maxillomandibular registration is necessary to
      ensure a satisfactory long-term clinical outcome. The transfer of the exact
      position of the implants to the working cast is even more important because
      implants lack the mobility of natural teeth. There are displacement differences
      between implants and natural teeth under occlusal force. The FBI technique may
      compensate for this difference in accuracy. CONCLUSION: Using the FBI technique,
      a precise prosthesis could be produced by completing simultaneously the
      maxillomandibular registration, impression and FGP.

PMID- 22609224
TI  - Evaluation of the electrocardiogram in identifying and quantifying lateral
      involvement in nonanterior wall infarction using cardiovascular magnetic
      resonance imaging.
AB  - PURPOSE: The objective of this study was to assess the involvement and extent of
      lateral wall myocardial infarction (MI) in patients with a first nonanterior wall
      MI, as reflected by changes in precordial leads. Delayed enhancement cardiac
      magnetic resonance imaging was used as a gold standard to localize and quantify
      myocardial scar tissue. METHODS: Electrocardiogram and cardiac magnetic resonance
      were studied in 56 patients. Areas involved were related to QRS changes in
      precordial leads. RESULTS: Significant correlations were found between lateral
      wall involvement and R waves in V(1) and V(6) (P = 0.009-0.022). For patients
      with circumflex branch occlusions, the MI size of the apical and lateral segments
      correlated strongly with the characteristics of R waves in V(1) and V(2) (P =
      0.001-0.034). CONCLUSIONS: Tall and broad R waves in V(1) reflect lateral wall
      MI, especially in circumflex occlusions.

PMID- 22609225
TI  - Differential effects of busulfan on gonadal development in five divergent anuran
      species.
AB  - The aim of this paper was to investigate the effects of germ cell depletion on
      the sexual differentiation of gonads in five anuran species. We used busulfan to
      eliminate the germ cells. Our results indicate that germ cells are not required
      for gonadal ridge formation or the development of the undifferentiated gonads. We
      observed a gradual degeneration of gonads in studied species and the
      transdifferentiation of the whole gonads into large fat bodies in Xenopus laevis.
      In the latter the sexual differentiation of gonads or seminiferous tubules were
      not impaired in the absence of germ cells. Thus, the X. laevis may serve as a
      model to study the human Del Castillo syndrome. Our study shows that in anuran
      amphibians the germ cells are not necessary for the formation of the testis, but
      they are crucial for development of the ovaries and are required for the
      maintenance of the gonadal structure.

PMID- 22609226
TI  - A multifaceted model for risk assessment of violent behaviour in acutely admitted
      psychiatric patients.
AB  - Violence risk assessment instruments are mainly based on historical and clinical
      risk factors. Biological factors have been related to violent behaviour but
      hardly used in risk assessment. A recent study indicated that both low total
      cholesterol (TC) and the patients' own estimates about their risk of future
      violent behaviour, the Self-report Risk Scale (SRS), significantly predicted
      violent behaviour during hospital stay and the first 3 months after discharge
      from an acute psychiatric department. Our aim was to investigate whether
      combining three methods, a screening instrument for risk of violence (V-RISK-10),
      low TC and the SRS, into one multifaceted risk assessment model may enhance
      predictive validity. This prospective naturalistic study involved 134 of all
      (489) acutely admitted patients to a general psychiatric hospital during 1 year.
      Low TC, SRS and V-RISK-10 at admission were prospectively compared with recorded
      violence during hospital stay and the first 3 months after discharge. The
      multifaceted risk assessment model yielded a significant increase in explained
      variance beyond that of the V-RISK-10. AUC values were higher, but differences
      were not significant. The biopsychosocial approach to violence risk assessment
      seems promising, but further studies are needed to test the feasibility and
      predictive validity of multifaceted models.

PMID- 22609227
TI  - Bone marrow-derived mesenchymal stem cells differentiate to hepatic
      myofibroblasts by transforming growth factor-beta1 via sphingosine
      kinase/sphingosine 1-phosphate (S1P)/S1P receptor axis.
AB  - Sphingosine kinase (SphK) is involved in numerous biological processes, including
      cell growth, proliferation, and differentiation. However, whether SphK
      participates in the differentiation of bone marrow-derived mesenchymal stem cells
      (BMSCs) to myofibroblasts has been unknown. In a carbon tetrachloride-treated
      mouse model, SphK1 was expressed in BMSCs in damaged liver. Furthermore, mRNA
      expression of both SphK1 and transforming growth factor beta1 (TGF-beta1) was
      significantly increased after liver injury, with a positive correlation between
      them. The SphK inhibitor SKI significantly blocked BMSC differentiation to
      myofibroblasts during liver injury (the proportion of BMSC-derived myofibroblasts
      decreased markedly, compared with no SKI treatment) and attenuated the extent of
      liver fibrosis. Using primary mouse BMSCs, we demonstrated that TGF-beta1 induced
      BMSC differentiation to myofibroblasts, accompanied by the up-regulation of SphK1
      and modulation of sphingosine 1-phosphate (S1P) receptor (S1PR) expression.
      Notably, pharmacological or siRNA-mediated inhibition of SphK1 abrogated the
      prodifferentiating effect of TGF-beta1. Moreover, using either S1PR subtype
      specific antagonists or specific siRNAs, we found that the prodifferentiating
      effect of TGF-beta1 was mediated by S1PR(1) and S1PR(3). These data suggest that
      SphK1 activation by TGF-beta1 leads to differentiation of BMSCs to myofibroblasts
      mediated by S1PR(1) and S1PR(3) up-regulation, thus providing new information on
      the mechanisms by which TGF-beta1 gives rise to fibrosis and opening new
      perspectives for pharmacological treatment of liver fibrosis.

PMID- 22609228
TI  - Hypophosphatemic rickets is associated with disruption of mineral orientation at
      the nanoscale in the flat scapula bones of rachitic mice with development.
AB  - Metabolic bone disorders such as rickets are associated with altered in vivo
      muscular force distributions on the skeletal system. During development, these
      altered forces can potentially affect the spatial and temporal dynamics of
      mineralised tissue formation, but the exact mechanisms are not known. Here we
      have used a murine model of hypophosphatemic rickets (Hpr) to study the
      development of the mineralised nanostructure in the intramembranously ossifying
      scapulae (shoulder bone). Using position-resolved scanning small angle X-ray
      scattering (SAXS), we quantified the degree and direction of mineral
      nanocrystallite alignment over the width of the scapulae, from the load bearing
      lateral border (LB) regions to the intermediate infraspinous fossa (IF) tissue.
      These measurements revealed a significant (p<0.05) increase in mineral
      nanocrystallite alignment in the LB when compared to the IF region, with
      increased tissue maturation in wild-type mice; this was absent in mice with
      rickets. The crystallites were more closely aligned to the macroscopic bone
      boundary in the LB when compared to the IF region in both wild type and Hpr mice,
      but the degree of alignment was reduced in Hpr mice. These findings are
      consistent with a correlation between the nanocrystallites within fibrils and in
      vivo muscular forces. Thus our results indicate a relevant mechanism for the
      observed increased macroscopic deformability in rickets, via a significant
      alteration in the mineral particle alignment, which is mediated by an altered
      spatial distribution of muscle forces.

PMID- 22609230
TI  - High detection rate of human papillomavirus in anal brushings from women
      attending a proctology clinic.
AB  - OBJECTIVES: To study human papillomavirus (HPV) anal infection in anal brushings
      from women attending a proctology clinic, and compare results with those obtained
      from paired cervical brushings. METHODS: Women attending a university hospital
      proctology clinic for anal conditions or as part of a screening campaign, were
      enrolled consecutively, excluding those reporting previous HPV-related
      pathologies. HPV genotypes in anal and cervical brushings were determined by
      sequencing and, in most cases, type-specific viral loads were measured. RESULTS:
      HPV DNA was detected in 28.3% of anal brushings, with 47.4% of HPV genotypes
      being high risk. Cervical HPV detection was at almost the same rate but HPV
      status was discordant in about half those women with at least one positive
      specimen. Abnormal cytological findings were more common in anal than in cervical
      samples, in particular in the proctology outpatients. Viral load measurements
      excluded the existence of a multiple infection with genotypes detected in
      discordant anal- and cervical-paired samples and showed a significant correlation
      between anal and cervical paired concordant samples. CONCLUSIONS: The high rate
      of HPV detection in anal brushings that is not usually related to HPV positivity
      in cervical brushings could provide support for offering HPV DNA tests to women
      attending proctology clinics.

PMID- 22609229
TI  - A phase Ib, dose-finding study of erlotinib in combination with a fixed dose of
      pertuzumab in patients with advanced non-small-cell lung cancer.
AB  - BACKGROUND: Pertuzumab, a dimerization inhibitor of human epidermal growth factor
      receptor 2 (HER2), has demonstrated pharmacodynamic activity, with stable disease
      in non-small-cell lung cancer. Combining erlotinib and pertuzumab may enhance
      antitumor activity. This study aimed to establish the recommended dosing of the
      erlotinib and pertuzumab combination; assess safety, preliminary efficacy, and
      pharmacokinetics; and analyze biomarkers. PATIENTS AND METHODS: Fifteen patients
      with stage IIIb/IV non-small-cell lung cancer who failed chemotherapy were
      recruited. The patients received erlotinib (days -8 to -1), then combination
      therapy (21-day cycles for 6 cycles). Pertuzumab was given intravenous at 840 mg,
      then 420 mg once every three weeks, with erlotinib given daily (100 or 150 mg).
      RESULTS: No dose-limiting toxicities were observed. Adverse events were generally
      grade 1/2 and manageable. The objective response rate was 20% (3/15 patients; 2
      responders had mutant HER1, 1 responder had wild-type HER1), median overall
      progression-free survival was 9.3 weeks. High HER1, HER2, and HER3 messenger RNA
      expression correlated with increased progression-free survival. Combination
      therapy did not affect erlotinib's pharmacokinetics; however, pertuzumab mean
      exposures (maximum concentration, 231 mg/L; area under the concentration-time
      curve from 0 to 21 days, 1780 mg*d/L) were slightly higher than in previous
      studies. CONCLUSIONS: Combination therapy was well tolerated in patients with
      good performance status, with encouraging efficacy. A loading dose of pertuzumab
      840 mg followed by 420 mg once every three weeks plus daily erlotinib 150 mg
      appears to be the most appropriate regimen for this combination.

PMID- 22609231
TI  - Flutamide, an androgen receptor antagonist, improves heatstroke outcomes in mice.
AB  - Flutamide has been used as an adjunct for decreasing the mortality from
      subsequent sepsis. Heatstroke resembles septic shock in many aspects. We
      hypothesized that heat-induced multiple organ dysfunction syndromes and lethality
      could be reduced by flutamide therapy. In heatstroke groups, mice were exposed to
      whole body heating (41.2 degrees C, for 1h) in a controlled-environment chamber.
      The heat-stressed mice were returned to normal room temperature (24 degrees C)
      after whole body heating. Mice still alive on day 4 of WBH treatment were
      considered survivors. Physiological and biochemical parameters were monitored for
      2.5h post-WBH. Heatstroke mice were subcutaneously treated with flutamide (12.5
      50mg/kg body weight in 0.05 ml) or vehicle solution (0.05 ml/kg body weight) once
      daily for 3 consecutive days post-WBH. We evaluated the effect of flutamide in
      heatstroke mice and showed that flutamide significantly (i) attenuated
      hypothermia, (ii) reduced the number of apoptotic cells in the hypothalamus, the
      spleen, the liver, and the kidney, (iii) attenuated the plasma index of toxic
      oxidizing radicals (e.g., nitric oxide metabolites and hydroxyl radicals), (iv)
      diminished the plasma index of the organ injury index (e.g., lactate
      dehydrogenase), (v) attenuated plasma systemic inflammation response molecules
      (e.g., tumor necrosis factor-alpha and interleukin-6), (vi) reduced the index of
      infiltration of polymorphonuclear neutrophils in the lung (e.g., myeloperoxidase
      activity), and (vii) allowed three times the fractional survival compared with
      vehicle. Thus, flutamide appears to be a novel agent for the treatment of mice
      with heatstroke or patients in the early stage of heatstroke.

PMID- 22609232
TI  - Mycophenolate mofetil inhibits macrophage infiltration and kidney fibrosis in
      long-term ischemia-reperfusion injury.
AB  - Immunosuppressants have been widely used in renal transplantation, in which
      ischemia-reperfusion injury is inevitable. Mycophenolate mofetil (MMF) is a
      relative novel immunosuppressant and also attenuates ischemia-reperfusion injury
      in the acute phase, but its long-term effects are still obscure. Unilateral renal
      ischemia-reperfusion injury model was established in Sprague-Dawley rats and 30
      mg/kg/day MMF or natural saline was administered a day before the surgery. Renal
      function was monitored, and histological changes and fibrosis in the kidney were
      evaluated in both short and long terms. TGF-beta1 secretion and MCP-1 expression
      were determined by immunohistochemistry and real-time PCR respectively. The
      infiltration of macrophages in renal tissues was also assessed by fluorescence
      activated cell sorting (FACS). MMF treatment significantly improved renal
      function in ischemia-reperfusion injury rats in the short and long-term and also
      effectively prevented interstitial fibrosis. TGF-beta1 secretion and MCP-1
      expression in the renal tissue of MMF-treated rats were much lower than those in
      natural saline-treated rats, with much less macrophage infiltration as well. MMF
      treatment effectively prevented the deterioration of renal function and
      interstitial fibrosis in ischemia-reperfusion injury rats, which may be
      associated with decreased TGF-beta1, MCP-1 and macrophages. These results provide
      evidence for the choice of MMF in the renal transplant patients not only for
      acute renal injury but also for long-term survival of renal allograft.

PMID- 22609233
TI  - [The training bubble].

PMID- 22609234
TI  - Implantation of unmarked regulatory and metabolic modules in Gram-negative
      bacteria with specialised mini-transposon delivery vectors.
AB  - Engineering of robust and safe microbial cell factories requires genetic tools
      somewhat different from those traditionally used for laboratory-adapted
      microorganisms. We took advantage of the properties of broad-host-range mini-Tn5
      vectors and two regulated expression systems (LacI(Q)/P(trc) and XylS/Pm),
      together with FRT-flanked, excisable antibiotic resistance determinants, to
      generate a set of vectors for the delivery of gene(s) into the chromosome of Gram
      negative bacteria. This arrangement of modular elements allows the cloning and
      subsequent markerless insertion of expression cargoes and leaves behind an
      antibiotic-sensitive host upon the action of the yeast Flp recombinase. We
      engineered a Pseudomonas putida KT2440 Pm::gfp strain that displayed strong
      fluorescence upon exposure to 3-methylbenzoate, a XylS effector, and allowed us
      to examine the performance of the Pm promoter at the single cell level. We also
      reconstructed a device for sugar transport and phosphorylation in Escherichia
      coli independent of the native phosphoenolpyruvate-dependent phosphotransferase
      system by the stable implantation of genes derived from the obligate anaerobe
      Zymomonas mobilis. In both cases, the information carried by the implanted genes
      was stably inherited in the absence of any selective pressure. Deliverable
      expression systems such as those described here will enhance the applicability of
      various Gram-negative bacteria in biocatalysis and environmental bioremediation.

PMID- 22609235
TI  - The 3p21.3 tumor suppressor RBM5 resensitizes cisplatin-resistant human non-small
      cell lung cancer cells to cisplatin.
AB  - OBJECTIVE: Increasing RBM5 levels inhibit tumor cell growth and promote
      apoptosis. In this study, we investigated the role of RBM5 in the cisplatin
      resistance observed in human lung non-small cell lung cancer cells and evaluated
      the effect of RBM5 modulation on cell growth inhibition and apoptosis induced by
      cisplatin in the parental non-small cell lung cancer cells A549 and their
      cisplatin resistant counterparts, A549/DDP cells. METHODS: RBM5 mRNA and protein
      expression in the A549 and A549/DDP cells was analyzed by semi-quantitative RT
      PCR and western blot. The A549/DDP cells were then transfected with a pcDNA3-RBM5
      plasmid, and an RBM5-specific siRNA was transfected into A549 cells, prior to
      treatment with cisplatin. Semi-quantitative RT-PCR and western blot analyses were
      performed to confirm the expression of RBM5 mRNA or protein, and knockdown of
      RBM5 mRNA or protein, respectively. MTT assays were used to evaluate
      chemosensitivity to cisplatin. Apoptosis was assessed by DAPI nuclear staining
      and flow cytometric analysis with an Annexin-V-FITC apoptosis kit. Cytosolic
      cytochrome c, cleaved caspase-3 and cleaved caspase-9 were detected by western
      blot. RESULTS: The expression of RBM5 mRNA and protein was significantly reduced
      in the A549/DDP cells compared with the A549 cells. Exogenous expression of RBM5
      by the pcDNA3-RBM5 resensitized the response of A549/DDP to cisplatin, resulting
      in a significant increase in tumor-suppressing activity induced by cisplatin. In
      contrast, downregulation of RBM5 with siRNA in the A549 cells inhibited cisplatin
      induced apoptosis. We also found that the RBM5-enhanced chemosensitivity was
      associated with the release of cytochrome c into the cytosol, activation of
      caspase-9 and the downstream marker caspase-3. CONCLUSION: Our results
      demonstrate that RBM5 may serve as a biomarker with the ability to predict a
      response to cisplatin. It may also act as a prognostic indicator in lung cancer
      patients. Our findings suggest that there may be clinical utility for ectopic
      RBM5 such as enhancing and resensitizing nonresponders to cisplatin.

PMID- 22609236
TI  - Mild hypothermia facilitates the expression of cold-inducible RNA-binding protein
      and heat shock protein 70.1 in mouse brain.
AB  - An appropriate thermal control system is essential for maintaining brain
      homeostasis. Hypothermia is a decrease in core body temperature that occurs when
      the thermoregulatory responses of homeothermic animals are impaired by
      environmental and situational influences, such as cold ambience and anesthesia.
      In recent years, hypothermia has been used for medical treatment, i.e.,
      therapeutic hypothermia, for patients with stroke, traumatic brain injury, and
      heart surgery. However, the target molecules acting during hypothermia have not
      been identified. To understand the molecular mechanisms, we generated a mouse
      model of mild hypothermia (1 degrees C-2 degrees C below normal), and analyzed
      the expression of several genes. After mice were exposed to cold for 24 and 48 h,
      their rectal temperature reached 33 degrees C-35 degrees C. Then, using real-time
      quantitative PCR, we analyzed the mRNA expression levels of c-fos, cold-inducible
      RNA-binding protein (CIRP), heat shock protein (hsp) 70.1, oxytocin, and
      representative inflammatory cytokines, i.e., tumor necrosis factor (TNF)-alpha
      and interleukin (IL)-6 in target organs. Importantly, we found that the
      expression levels of CIRP and hsp70.1 were elevated in the olfactory bulb within
      48 h. In the hypothalamus, CIRP expression levels increased and were followed by
      an increase in hsp70.1 expression. Meanwhile, TNF-alpha and IL-6 expression
      decreased gradually over 24 and 48 h in the olfactory bulb and hypothalamus.
      These specific expression profiles, i.e., enhanced CIRP and hsp70.1 expression
      and depressed cytokine expression, suggest that they could regulate apoptosis
      related to the cytokine signaling.

PMID- 22609237
TI  - Epidemiology and outcome of major postoperative infections following cardiac
      surgery: risk factors and impact of pathogen type.
AB  - BACKGROUND: Major postoperative infections (MPIs) are poorly understood
      complications of cardiac surgery. We examined the epidemiology, microbiology, and
      outcome of MPIs occurring after cardiac surgery. METHODS: The study cohort was
      drawn from the Society of Thoracic Surgeon National Cardiac Database and
      comprised adults who underwent cardiac surgery at 5 tertiary hospitals between
      2000 and 2004. We studied the incidence, microbiology, and risk factors of MPI
      (bloodstream or chest wound infections within 30 days after surgery), as well as
      30-day mortality. We used multivariate regression analyses to evaluate the risk
      of MPI and mortality. RESULTS: MPI was identified in 341 of 10,522 patients
      (3.2%). Staphylococci were found in 52.5% of these patients, gram-negative
      bacilli (GNB) in 24.3%, and other pathogens in 23.2%. High body mass index,
      previous coronary bypass surgery, emergency surgery, renal impairment,
      immunosuppression, cardiac failure, and peripheral/cerebrovascular disease were
      associated with the development of MPI. Median postoperative duration of
      hospitalization (15 days vs 6 days) and mortality (8.5% vs 2.2%) were higher in
      patients with MPIs. Compared with uninfected individuals, odds of mortality were
      higher in patients with S aureus MPIs (adjusted odds ratio, 3.7) and GNB MPIs
      (adjusted odds ratio, 3.0). CONCLUSIONS: Staphylococci accounted for the majority
      of MPIs after cardiac surgery. Mortality was higher in patients with
      Staphylococcus aureus- and GNB-related MPIs than in patients with MPIs caused by
      other pathogens and uninfected patients. Preventive strategies should target
      likely pathogens and high-risk patients undergoing cardiac surgery.

PMID- 22609238
TI  - Cerebellar rTMS stimulation may induce prolonged clinical benefits in essential
      tremor, and subjacent changes in functional connectivity: an open label trial.
AB  - BACKGROUND: Cerebello-thalamo-cortical (CTC) pathways dysfunction is involved in
      pathological oscillations causing tremor in essential tremor (ET). Low-frequency
      (1 Hz) repetitive transcranial magnetic stimulation (rTMS) of the cerebellum can
      effectively modulate the cerebellar output. OBJECTIVE: As one session of rTMS can
      induce a brief improvement, we hypothesized that repeated sessions might have a
      cumulative and potentially long-term therapeutic effect on ET. We assessed, in an
      open label trial, the efficacy of one-week rTMS treatment on tremor and on the
      motor-CTC dysfunction in ET patients. METHODS: Resting-state fMRI functional
      connectivity was used as an indicator of CTC network integrity in 11 ET patients
      and 11 healthy subjects. Resting-state fMRI connectivity was quantified at
      baseline in patients and control subjects between the cerebellum and the motor
      network, and between the cerebellum and the default brain network (DBN) taken as
      control. The fMRI study was repeated in patients after 5 days of bilateral 1 Hz
      rTMS applied to the posterior cerebellar cortex. Tremor was assessed clinically
      (Fahn-Tolosa-Marin scale) and quantified using electromyographic and
      accelerometric recordings at baseline (day 1, before the cerebellar stimulation)
      and after the end of the cerebellar stimulation period at day 5, day 12 and day
      29. RESULTS: Repeated rTMS over the cerebellum significantly improved total and
      specific (tremor, drawing, functional disability) scores, and reduced tremor
      amplitude (P < 0.006). It also re-established the defective information
      processing in the CTC network (P(Delta|y) > 0.909), but not in the DBN. The
      effects persisted for 3 weeks after the last session. CONCLUSION: Cerebellar
      stimulation could be an effective treatment option for patients with severe
      essential tremor.

PMID- 22609239
TI  - What can I do? Recommendations for responding to issues identified by patient
      reported outcomes assessments used in clinical practice.
AB  - There is increased interest in using patient-reported outcome (PRO) measures in
      routine clinical practice to improve patient management. The effectiveness of
      this intervention may be facilitated by providing suggestions to clinicians on
      how to address issues identified by the PROs. We sought to develop
      recommendations for clinicians on how to respond to issues covered by common
      cancer PRO questionnaires, including functional problems (eg, physical, social,
      emotional), symptoms (eg, diarrhea, pain), and needs (eg, patient care and
      support, information). The recommendations would be incorporated into a Web-based
      system for PRO assessment and reporting in use at our large, academic cancer
      center. To develop the recommendations, we conducted a multiphase,
      multidisciplinary, consensus process. We reviewed the literature and conducted
      one-on-one interviews with experts from various disciplines. Experts included
      medical oncologists, radiation oncologists, nurses, an internist, a palliative
      care specialist, an outcomes researcher, a chaplain, a social worker, and patient
      advocates. These interviews elicited the experts' recommendations for addressing
      problems in common PRO domains. Finally, we held a panel meeting attended by all
      the experts to attain consensus on the recommendations. The final consensus
      suggestions recommend further assessment of the problem as a first step.
      Treatment suggestions range from medication adjustments to lifestyle
      modifications to referrals to other disciplines. Further research will test
      whether clinicians find these suggestions useful for patient management.

PMID- 22609240
TI  - Decreased humoral antibody episodes of acute renal allograft rejection in
      recipients expressing the HLA-DQbeta1*0202 allele.
AB  - The present investigation was designed to show the effect of human leukocyte
      antigen (HLA) class II molecular allelic specificities in the recipient on the
      induction of humoral antibody rejection, identified by C4d peritubular capillary
      staining, as well as specific antibody identified by Luminex technology. Major
      histocompatibility complex (MHC) class II molecules are expressed on dendritic
      cells, macrophages, and B lymphocytes and they present antigenic peptides to CD4
      positive T lymphocytes. Human renal peritubular and glomerular capillaries
      express class II MHC molecules upon activation. Expression of class II molecules
      on renal microvascular endothelial cells exposes them to possible interaction
      with specific circulating antibodies. We hypothesize that HLA-DQbeta1*0202
      expression in recipients decreases the likelihood of antibody-mediated renal
      allograft rejection. We found that 80% (=25) of DQ2 positive haplotype recipients
      failed to induce humoral antibody renal allograft rejection and 20% (n=25) of DQ2
      positive haplotype recipients induced humoral antibody renal allograft rejection
      (p=0.008). By contrast, 48% (n=46) of DQ2 negative haplotype recipients failed to
      induce a humoral antibody component of renal allograft rejection and 52% (n=46)
      of DQ2 negative haplotype recipients induced humoral antibody-mediated renal
      allograft rejection. Our results suggest that recipients who express the
      DQbeta1*0202 allele are less likely to induce a humoral antibody component of
      acute renal allograft rejection than are those expressing DQ1, DQ3, or DQ4
      alleles. DQbeta1*0202 allele expression in recipients could possibly be
      protective against acute humoral allograft rejection and might serve as a future
      criterion in recipient selection and in appropriate therapy for acute renal
      rejection episodes.

PMID- 22609241
TI  - High mobility group box chromosomal protein 1 in acute-on-chronic liver failure
      patients and mice with ConA-induced acute liver injury.
AB  - High mobility group box chromosomal protein 1 (HMGB1) is an important
      proinflammatory molecule in many inflammatory disorders, but little is known
      about its role in acute-on-chronic liver failure (ACLF). Here, we investigated
      the relationship between the expression of HMGB1 and the disease onset and
      severity of ACLF patients and mice with acute liver injury/failure induced by
      concanavalin A (ConA). Peripheral blood mononuclear cells (PBMCs) and serum from
      ACLF patients were collected, and a mouse model of acute liver injury/failure was
      induced by ConA. HMGB1 mRNA expression in patient PBMCs or in murine livers and
      serum HMGB1 protein in ACLF patients and mice were assayed by RT-PCR and Western
      blotting, respectively. HMGB1 translocation in hepatocytes of ConA-treated mice
      was assessed by immunohistochemical staining. Up-regulated HMGB1 mRNA levels in
      PBMCs and accumulated protein in serum were both correlated with disease severity
      in ACLF patients. In the animal model, HMGB1 levels increased at 4 h and reached
      its peak value at 8-12 h after challenge with ConA, which suggests that HMGB1 is
      a relatively late proinflammatory cytokine compared with TNF-alpha. Translocation
      of HMGB1 from the nucleus to the cytoplasm in hepatocytes was correlated with the
      severity of liver injury in mice. While specific anti-HMGB1 antibodies and
      nicotine protected mice from acute liver injury/failure by reducing mortality and
      improving liver tissue injury, treatment with recombinant HMGB1 led to an
      increased mortality due to ConA challenge. Thus, the data from the present study
      suggest that HMGB1 plays a critical role in the systemic inflammation of ACLF and
      could be a potential therapeutic target in the treatment of ACLF.

PMID- 22609242
TI  - A model for cardiomyocyte cell death: insights into mechanisms of oncosis.
AB  - It is now known that there are at least two basic patterns of cell injury
      progressing to cell death: cell injury with swelling, known as oncosis, and cell
      injury with shrinkage, known as apoptosis. Both types of cell death are
      "programmed" in the sense that the genetic information and many of the enzymes
      and other factors pre-exist in the cell. Previous investigation has pointed to
      cardiomyocyte ischemic injury evolving as the oncotic pattern of injury, although
      apoptosis has also been implicated. This study was designed, using a unique cell
      model system, to gain insight into the molecular events of anticancer agent
      induced cardiomyocyte injury. Cardiomyocytes exposed for 2 h to 1.5 MUg/ml
      sanguinarine consistently displayed the morphology of apoptosis in over 80% of
      cells, whereas a higher dose of 25 MUg/ml at 2 h yielded the pattern of oncosis
      in over 90% of cells. Microarray analysis revealed altered expression of 2514
      probes in sanguinarine-induced oncosis and 1643 probes in apoptosis at a level of
      significance of p<0.001. Some of the inductions such as perforin were found to be
      higher than 11-fold in oncosis. When perforin was blocked by perforin-specific
      siRNA we found a reduction in oncotic cell death. These results strengthen the
      notion that oncosis is not representative of nonspecific necrosis, but
      constitutes a genetically controlled form of "programmed cell death"; and also
      that oncosis might represent a pathogenetic mechanism of cardiomyocyte injury.
      This is also the first demonstration of the involvement of perforin in
      cardiomyocyte oncosis.

PMID- 22609243
TI  - Ticks and tick-borne pathogens on the rise.

PMID- 22609244
TI  - Preschoolers' fantasy-reality distinctions of emotional events.
AB  - Research suggests that emotions influence children's ability to discern fantasy
      from reality; however, reasons for this association remain unknown. The current
      research sought to better understand the mechanisms underlying children's
      distinctions by examining the roles discrete emotions and context have in 3- to 5
      year-olds' evaluations of fantasy and reality. In Study 1, children's fantasy
      reality distinctions of images depicting happy, frightening, or sad events were
      obtained under two conditions: Children responded freely or were motivated to
      respond accurately. When responding freely, older children reported that happy
      and sad fantastic and real events could occur but frightening events could not.
      When motivated to respond accurately, children's accuracy improved for fantasy
      but not for reality. Study 2 examined real events exclusively and found that
      children may lack the knowledge that frightening, but not happy or sad, real
      events can occur. The findings provide new insight into how emotions affect
      children's fantasy-reality distinctions.

PMID- 22609245
TI  - Dysfunctional HDL: a novel important diagnostic and therapeutic target in
      cardiovascular disease?
AB  - High density lipoprotein (HDL) has many properties, which contribute to its
      atheroprotective role. However, some recent clinical trials have identified
      subjects with the progression of atherosclerosis despite normal levels of HDL
      cholesterol. This raises the question if all subfractions of HDL have the same
      properties. Moreover, recent investigations have shown that both acute and
      chronic inflammation may lead to structural and functional changes of HDL, which
      render the particles proinflammatory. Although therapeutic agents that increase
      HDL levels are now quite well established it is not clear whether they influence
      HDL quality. We review the current state of knowledge on the properties of HDL
      and factors/therapeutic agents which may restrain the transformation of normal
      HDL into dysfunctional HDL.

PMID- 22609246
TI  - Interleukin-10 inhibits lipopolysaccharide-induced upregulation of tissue factor
      in canine peripheral blood monocytes.
AB  - The potentially fatal hemostatic disorder of disseminated intravascular
      coagulation (DIC) is initiated in bacterial sepsis by lipopolysaccharide (LPS)
      induced tissue factor (TF) expression on monocytes. Interleukin-10 (IL-10) is a
      potent inhibitory cytokine that downregulates monocyte inflammatory and
      procoagulant responses. We hypothesized that canine recombinant IL-10 (rIL-10)
      would inhibit LPS-induced TF upregulation on canine monocytes in a dose-dependent
      manner. Canine peripheral blood mononuclear cells (PBMC), obtained by double
      density gradient centrifugation, and monocytes, purified from PBMC by
      immunomagnetic bead separation with an anti-canine CD14 antibody (Ab), were
      stimulated in suspension with LPS (0.1-1000 ng/mL) for various times. Recombinant
      IL-10 (10-5000 pg/mL) was added with LPS or up to 2h later. Tissue factor
      procoagulant activity was measured by cleavage of a chromogenic substrate by
      activated Factor X generated by the TF-factor VII complex. We found that rIL-10,
      when given concurrently or 1h after LPS, strongly inhibited LPS-induced TF
      procoagulant activity in canine PBMC and monocytes. This inhibition was dose
      dependent and blocked by an anti-canine IL-10 Ab. Our results indicate that rIL
      10 effectively inhibits LPS-induced TF upregulation in canine monocytes and could
      potentially be useful in limiting the development of DIC in dogs with
      endotoxemia.

PMID- 22609247
TI  - Negative reinforcement reveals non-evoked ongoing pain in mice with tissue or
      nerve injury.
AB  - Patients with chronic pain experience spontaneous or ongoing pain as well as
      enhanced sensitivity to evoked stimuli. Spontaneous or ongoing pain is rarely
      evaluated in preclinical studies. In fact, it remains controversial whether
      ongoing or spontaneous pain even develops in mice after tissue or nerve injury.
      This study tested a hypothesis that negative reinforcement can be used to unmask
      the presence of pain in mice with tissue or nerve injury. We found that spinal
      administration of clonidine or lidocaine did not elicit conditioned place
      preference (CPP) in uninjured or sham-operated mice. However, these agents
      produced CPP in mice with chronic inflammation induced by complete Freund's
      adjuvant (CFA) or following L5/L6 spinal nerve ligation (SNL). These data
      indicate the presence of non-evoked (ie, stimulus-independent) ongoing pain in
      mice with chronic inflammation (CFA) or following nerve injury (SNL). In
      addition, this study validates the use of negative reinforcement to unmask non
      evoked ongoing pain in mice. Given the existence of a large collection of
      transgenic and knockout mice, our data show the application of this approach to
      elucidate molecular mechanisms underlying non-evoked pain and to contribute to
      drug discovery for pain. PERSPECTIVE: We demonstrated the presence of non-evoked
      ongoing pain in mice with chronic inflammation or following nerve injury. The
      study also validates the use of negative reinforcement to unmask non-evoked pain
      in mice. We propose to apply this approach to identify molecular mechanisms and
      effective drugs for chronic pain.

PMID- 22609249
TI  - Aldosterone, oxidative stress, and NF-kappaB activation in hypertension-related
      cardiovascular and renal diseases.
AB  - The mineralocorticoid aldosterone regulates electrolyte and fluid balance and is
      involved in blood pressure homoeostasis. Classically, it binds to its
      intracellular mineralocorticoid receptor to induce expression of proteins
      influencing the reabsorption of sodium and water in the distal nephron.
      Aldosterone gained special attention when large clinical studies showed that
      blocking its receptor in patients with cardiovascular diseases reduced their
      mortality. These patients present increased plasma aldosterone levels. The exact
      mechanisms of the potential toxic effects of aldosterone leading to
      cardiovascular damage are not known yet. The observation of reduced nitric oxide
      bioavailability in hyperaldosteronism implied the generation of oxidative stress
      by aldosterone. Subsequent studies confirmed the increase of oxidative stress
      markers in patients with chronic heart failure and in animal models of
      hyperaldosteronism. The effects of reactive oxygen species have been related to
      the activation of transcription factors, such as NF-kappaB. This review
      summarizes the present-day knowledge of aldosterone-induced oxidative stress and
      NF-kappaB activation in humans and different experimental models.

PMID- 22609248
TI  - What really happens in the neutrophil phagosome?
AB  - Current viewpoints concerning the bactericidal mechanisms of neutrophils are
      reviewed from a perspective that emphasizes challenges presented by the inability
      to duplicate ex vivo the intracellular milieu. Among the challenges considered
      are the influences of confinement upon substrate availability and reaction
      dynamics, direct and indirect synergistic interactions between individual toxins,
      and bacterial responses to stressors. Approaches to gauging relative
      contributions of various oxidative and nonoxidative toxins within neutrophils
      using bacteria and bacterial mimics as intrinsic probes are also discussed.

PMID- 22609251
TI  - [Musculoskeletal imaging in the SERAM's catalogue of services].

PMID- 22609252
TI  - In vivo electroporation enhances immunogenicity and protection against influenza
      A virus challenge of an M2e-HSP70c DNA vaccine.
AB  - There is a growing concern regarding continuous risk of emerging a new influenza
      pandemic. It is highlighted the need for novel vaccination techniques that
      quickly and effectively employed to respond to such threats. Although, DNA
      vaccine is a simple and effective approach to induce antigen specific immune
      responses, their potency requires further improvement. DNA vaccine encoding
      conserved antigen of influenza virus could provide protection in various animal
      models. Therefore, we constructed a plasmid vector encoding M2e-HSP70c sequences,
      pcDNA/MHc, as a candidate for universal influenza vaccine. The expression of
      newly constructed vectors was verified by transient transfection of mammalian
      cells (HEK293T cell line) and western blot analysis using commercial antibodies.
      Mice were injected subcutaneously (s.c.) by the help of electroporation (IEP) in
      the footpad area and boosted without IEP with 100 MUg of constructed vector.
      Furthermore, the potency of this construct to provoke humoral immune responses
      and its protectivity against lethal dose of viral challenge were evaluated. Based
      on our study, the fusion construct was immunogenic in mice and was able to confer
      both protection against lethal challenge of H1N1 virus and reduce viral load in
      lung homogenates of the infected mice.

PMID- 22609250
TI  - Role of inducible nitric oxide synthase in mitochondrial depolarization and graft
      injury after transplantation of fatty livers.
AB  - This study investigated the role of inducible nitric oxide synthase (iNOS) in
      failure of ethanol-induced fatty liver grafts. Rat livers were explanted 20 h
      after gavaging with ethanol (5 g/kg) and storing in UW solution for 24h before
      implantation. Hepatic oil red O staining-positive areas increased from ~2 to ~33%
      after ethanol treatment, indicating steatosis. iNOS expression increased ~8-fold
      after transplantation of lean grafts (LG) and 25-fold in fatty grafts (FG).
      Alanine aminotransferase release, total bilirubin, hepatic necrosis, TUNEL
      positive cells, and cleaved caspase-3 were higher in FG than LG. A specific iNOS
      inhibitor 1400W (5 MUM in the cold-storage solution) blunted these alterations by
      >42% and increased survival of fatty grafts from 25 to 88%. Serum nitrite/nitrate
      and hepatic nitrotyrosine adducts increased to a greater extent after
      transplantation of FG than LG, indicating reactive nitrogen species (RNS)
      overproduction. Phospho-c-Jun and phospho-c-Jun N-terminal kinase-1/2 (JNK1/2)
      were higher in FG than in LG, indicating more JNK activation in fatty grafts. RNS
      formation and JNK activation were blunted by 1400W. Mitochondrial polarization
      and cell death were visualized by intravital multiphoton microscopy of rhodamine
      123 and propidium iodide, respectively. After implantation, viable cells with
      depolarized mitochondria were 3-fold higher in FG than in LG and 1400W decreased
      mitochondrial depolarization in FG to the levels of LG. Taken together, iNOS is
      upregulated after transplantation of FG, leading to excessive RNS formation, JNK
      activation, mitochondrial dysfunction, and severe graft injury. The iNOS
      inhibitor 1400W could be an effective therapy for primary nonfunction of fatty
      liver grafts.

PMID- 22609253
TI  - What affects human papillomavirus vaccination rates? A qualitative analysis of
      providers' perceptions.
AB  - PURPOSE: To define factors that providers perceive as affecting their
      administration of human papillomavirus (HPV) vaccination in their clinical
      practices. METHODS: We conducted in-depth, qualitative interviews with 34
      pediatric and family medicine providers in four community health centers to
      explore providers' perceptions of factors that either enabled or impeded their
      ability to vaccinate their patients against HPV. RESULTS: Providers' self
      reported vaccination rates ranged from 25 to 95% (median, 75%) of the 11- to 26
      year-old females in their practices. Factors that enabled vaccination included
      providers' beliefs that HPV vaccines were safe and would provide important health
      benefits, structured visits that promoted vaccination, and coadministration of
      HPV with other recommended vaccines. Factors that impeded vaccination included
      safety concerns, a low perceived severity of HPV disease, lack of school
      mandates, and policies against coadministration of HPV and meningococcal
      vaccines. Providers who described more enabling factors than impeding factors
      reported vaccinating more of their patients. CONCLUSIONS: Provider perceptions
      around the ease or difficulty of providing HPV vaccination may influence their
      behavior when offering HPV vaccines to their patients.

PMID- 22609254
TI  - Patient education and emotional support practices in abortion care facilities in
      the United States.
AB  - PURPOSE: Little is known about how patient education and emotional support is
      provided at abortion facilities. This pilot study documents 27 facilities'
      practices in this aspect of abortion care. METHODS: We conducted confidential
      telephone interviews with staff from 27 abortion facilities about their
      practices. MAIN FINDINGS: The majority of facilities reported they rely primarily
      on trained nonclinician staff to educate patients and provide emotional support.
      As part of their informed consent and counseling processes, facilities reported
      that staff always provide patients with information about the procedure (96%),
      assess the certainty of their abortion decisions (92%), assess their feelings and
      provide emotional support (74%), and provide contraceptive health education
      (92%). Time spent providing these components of care varied across facilities and
      patients. When describing their facility's care philosophy, many respondents
      expressed support for "patient-centered," "supportive," "nonjudgmental" care.
      Eighty-two percent agreed that it is the facility's role to provide counseling
      for emotional issues related to abortion. CONCLUSIONS: All facilities valued
      informed consent, patient education, and emotional support. Although the majority
      of facilities considered counseling for emotional issues to be a part of their
      role, some did not. Future research should examine patients' preferences
      regarding abortion care and counseling and how different approaches to care
      affect women's emotional well-being after having an abortion. PRACTICE
      IMPLICATIONS: This information is important in light of current, widespread
      legislative efforts that aim to regulate abortion counseling, which are being
      proposed without an understanding of patient needs or facility practices.

PMID- 22609256
TI  - Ultrasound-promoted tosylation of oligo(ethylene glycols).
AB  - A series of oligo(ethylene glycols) was efficiently tosylated by ultrasound
      procedure within dichloromethane in the presence of triethylamine. Results show
      that sonochemical synthesis of oligo(ethylene glycol) ditosylates has a double
      advantage since it does not use catalysts and it drastically reduces the reaction
      time. This straightforward method represents an eco-friendly alternative to the
      traditional tosylation by pyridine synthesis.

PMID- 22609255
TI  - Reproductive cancer risk factors among Alaska Native women: the Alaska Education
      and Research Towards Health (EARTH) Study.
AB  - BACKGROUND: The purpose of this study was to provide estimates for the prevalence
      of reproductive cancer risk factors among Alaska Native (AN) women who enrolled
      in the Alaska Education and Research Towards Health (EARTH) Study from 2004 to
      2006. METHODS: A total of 2,315 AN women 18 years or older completed reproductive
      health questions as part of a comprehensive health history questionnaire. The
      reproductive health section included menstrual status (age at menarche and
      menopause), pregnancy and live birth history, use of hormonal contraception,
      hormone replacement therapy, and history of hysterectomy and/or oophorectomy.
      RESULTS: A total of 463 (20%) of women experienced menarche before age 12 with a
      decline in mean age at menarche by age cohort. More than 86% had been pregnant
      (mean number of pregnancies, 3.8; mean number of live births, 2.9). More than one
      half of women (58%) had their first live birth between the ages of 18 and 24.
      Almost 28% of participants had completed menopause, of whom 24% completed
      menopause after age 52. Fewer than half (43%) reported ever using hormone
      replacement therapy. Almost two thirds (62%) reported ever using oral
      contraceptives, and fewer reported ever using birth control shots (30%) or
      implants (10%). CONCLUSIONS: This study is unique in reporting reproductive
      health factors among a large group of AN women. These data show that AN women
      have selective protective factors for reproductive cancers, including low
      nulliparity rates, low use of menopausal estrogens, and common use of
      contraceptive hormones. However, analysis by age cohorts indicates decreasing age
      at menarche that might increase the risk for reproductive cancers among AN women
      in the future.

PMID- 22609257
TI  - Quantitative PCR detection for abalone shriveling syndrome-associated virus.
AB  - Haliotis diversicolor (small abalone) is an important seafood found along the
      southern coast of China. Since 1999, the yields of cultured abalone in China have
      been severely affected by an epidemic of continuous outbreaks of a fatal disease.
      A novel double-stranded DNA virus, abalone shriveling syndrome-associated virus
      (AbSV), was proven to be one of the main causative agent. Although the
      pathogenicity and genome of AbSV has been ascertained, the epidemiology of AbSV
      remains to be investigated. In this study, four pairs of AbSV-specific primers
      were designed on the basis of the AbSV genome, and were tested for their
      specificities and sensitivities in quantitative real-time PCRs (qPCRs) after
      optimization of the annealing temperature. The 3F3/3B3 primer pair was finally
      chosen with a good specificity and high efficiency of amplification, with a
      detection limit of about 10 copies of recombinant plasmid containing AbSV genes
      in a 20-MUL reaction mixture. In the detection of AbSV in abalone samples along
      the southern coast of China, most of the diseased samples had more than 80 virus
      copies in 1ng host genome DNA. AbSV was also demonstrated in mature hybrid (LY)
      and juvenile (JH) abalones from assays of healthy animals collected in recent
      years.

PMID- 22609258
TI  - Elevated serum beta2-GPI-Lp(a) complexes levels in children with nephrotic
      syndrome.
AB  - BACKGROUND: The complexes of beta2-glycoprotein I (beta2-GPI) with lipoprotein(a)
      [beta2-GPI-Lp(a)] exist in human circulation and are increased in serum from
      patients with some autoimmune diseases. This study aims to investigate the
      concentration of beta2-GPI-Lp(a) in serum of children with idiopathic nephrotic
      syndrome (NS) and its relationship with serum lipids, oxidized lipoprotein and
      renal function parameters to explore the potential of the complexes as an
      additional marker for evaluating pediatric NS. METHODS: Serum concentrations of
      beta2-GPI-Lp(a) complexes and oxidized Lp(a) [ox-Lp(a)] were measured by
      "Sandwich" ELISAs in 80 NS children and 82 age/sex-matched healthy controls. The
      levels of serum lipids and kidney parameters were also determined. Multivariate
      logistic regression analysis was performed to identify correlate of beta2-GPI
      Lp(a) and NS. RESULTS: The serum concentrations of beta2-GPI-Lp(a) complexes in
      children with NS were significantly higher than those in controls (median 0.95
      U/ml vs 0.28 U/ml, P<0.0001). Ox-Lp(a) levels were also markedly elevated (median
      14.55 mg/l vs 2.60 mg/l, P<0.0001] in NS children. The concentrations of beta2
      GPI-Lp(a) were positively correlated with ox-Lp(a) (r=0.246, P=0.028), but not
      with Lp(a) level, and the concentrations of ox-Lp(a) were positively related with
      Lp(a) (r=0.301, P=0.007) in NS children. Multivariate logistic regression
      analysis identified a positive association between NS and beta2-GPI-Lp(a)
      (OR=13.694, 95% CI 6.400-29.299, P<0.0001), after adjusting for kidney function
      parameters, serum lipids and ox-Lp(a). CONCLUSIONS: Elevated beta2-GPI-Lp(a)
      level was an independent and significant risk factor for pediatric NS and,
      enhanced Lp(a) oxidation partly contributes to the formation of beta2-GPI-Lp(a)
      complexes.

PMID- 22609259
TI  - The levels of circulating and urinary monocyte chemoattractant protein-1 are
      associated with chronic renal injury in obese men.
AB  - BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is a vital inflammatory
      marker of obesity. Whether obesity by itself increases the risk of chronic kidney
      injury and accelerates its progression is unknown. More importantly, it is
      unknown whether obesity could induce kidney injury by MCP-1. METHODS: We enrolled
      40 obese men and 26 healthy volunteers who served as controls. The degree of
      insulin resistance was evaluated by the homeostasis model assessment (HOMA-IR)
      method, and kidney function was determined based on the estimated glomerular
      filtration rate (eGFR), albuminuria, the concentration of serum cystatin C (S
      CysC), and the urinary cystatin C to creatinine ratio (UCCR). RESULTS: The obese
      subjects had significantly higher S-CysC concentration (1114+/-288 vs.962+/-169
      mg/L, p=0.021) and a higher UCCR (3.5+/-1.6 vs. 2.5+/-0.8 MUg/g, p=0.002) than
      those of controls. The concentration of circulating MCP-1 and the urinary MCP-1
      to creatinine ratio (UMCR) were higher in the obese group and were correlated
      with fat mass and HOMA-IR. Using stepwise multiple linear regression analysis,
      circulating MCP-1 concentration was found to be independently associated with the
      amount of S-CysC. In addition, the UMCR was independently associated with the
      UCCR. CONCLUSION: The concentrations of circulating and urinary monocyte
      chemoattractant protein-1 are associated with chronic renal injury in obese men.

PMID- 22609260
TI  - Serum interleukin-6 levels in response to methotrexate treatment in psoriatic
      patients.
AB  - BACKGROUND: Psoriasis is a chronic autoimmune hyperproliferative skin disease. In
      psoriasis, the cutaneous and systemic overexpression of various proinflammatory
      cytokines, such as interleukin-6 (IL-6) has been demonstrated. Methotrexate (MTX)
      has been used in the treatment of psoriasis. The aim of this study is to assess
      the effect of MTX on serum IL-6 levels and also to find the association between
      PASI score and IL-6 levels in psoriatic patients during MTX therapy. METHODS: We
      recruited 20 control subjects and 22 Psoriasis vulgaris patients for this study.
      The patients were treated with 7.5mg of methotrexate per week for 12 weeks. Folic
      acid was given at 5mg once daily except on the day of MTX for 12 weeks. There
      were 2 dropouts, because of increased liver enzyme levels. Blood samples were
      collected at three intervals (i.e., Day 0, 6 weeks, 12 weeks) from psoriatic
      patients and only once from control subjects. PASI score, biochemical and
      hematological parameters were assessed. Serum IL-6 level was analyzed by using
      ELISA. RESULTS: Biochemical and hematological parameters showed no significant
      changes. Serum IL-6 level and PASI score declined significantly (p<0.001) from
      Day 0 to 12 weeks of MTX treatment and also showed positive correlation before
      (r=0.992; p<0.000) and after (r=0.987; p<0.000) treatment with MTX. Out of 4
      clinical indices of PASI, only 2 indices namely Infiltration (I) and Desquamation
      (D) showed positive correlation with IL-6 before and after MTX treatment.
      CONCLUSION: The treatment response with MTX in psoriatic patients can be seen
      both at clinical and molecular levels.

PMID- 22609261
TI  - Ciglitazone inhibits cigarette smoke solution-induced inflammatory responses in
      human middle ear epithelial cells.
AB  - OBJECTIVE: Peroxisome proliferator activated receptor-gamma (PPAR-gamma), a
      member of the nuclear hormone receptor superfamily, plays an important role in
      the regulation of mucosal inflammation. The aim of this study was to investigate
      the anti-inflammatory effect of a PPAR-gamma agonist, ciglitazone, on cigarette
      smoke solution (CSS)-induced inflammation in human middle ear epithelial cell
      lines (HMEECs). DESIGN: HMEECs with or without ciglitazone pre-treatment were
      exposed to CSS in order to induce the inflammatory response. The suppressive
      effect of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha)
      and cyclooxygenase-2(COX-2), were evaluated using real-time polymerase chain
      reaction and Western blotting. RESULTS: Stimulation with CSS at 40 MUg/ml for 6 h
      resulted in a 4.1-fold increase in the expression of TNF-alpha mRNA in the
      HMEECs. CSS-induced up-regulation of TNF-alpha mRNA was decreased by more than
      2.8-fold in cells pre-treated with ciglitazone. The up-regulation of COX-2 mRNA
      and increased COX-2 protein expression induced by CSS were also inhibited by more
      than 3.7-fold with ciglitazone pre-treatment. CONCLUSIONS: These findings suggest
      that the inflammatory response induced by CSS could be inhibited by ciglitazone,
      a PPAR-gamma agonist, in HMEECs. As such, PPAR-gamma agonists may have
      therapeutic potential for the treatment of otitis media.

PMID- 22609262
TI  - Clinical cytogenetics in pediatric acute leukemia: an update.
AB  - Pediatric acute leukemias are generally characterized by recurrent numerical and
      structural chromosomal abnormalities, which are thought to be specifically
      associated with diagnosis and prognosis of both childhood acute lymphoblastic
      leukemia (ALL) and acute myeloid leukemia (AML). The identification of those
      chromosomal aberrations is clinically important because they are considered
      significant risk-stratifying markers. However there have been several instances
      in which they remain undetectable, possibly due to the low resolution of most
      genetic screening tools used. In the present review, the clinical significance of
      most chromosomal aberrations associated with pediatric ALL and AML as well as the
      current technology used for their identification is discussed.

PMID- 22609263
TI  - [Metformin-associated lactic acidosis: incidence, diagnosis, prognostic factors
      and treatment].
AB  - We describe the case of a patient with severe lactic acidosis, as well as
      presenting some data on its incidence, diagnosis, prognostic factors, and the
      most appropriate treatment. A 76 year-old male patient with diabetes on treatment
      with metformin, hypertension, dyslipaemia, and with mild cognitive impairment,
      was admitted to the Intensive Care Unit in a state of circulatory shock,
      requiring aggressive treatment with vasopressors and volume. The patient had
      acute kidney injury with an anuria of 3 days, probably secondary to dehydration
      to vomiting and to NSAIDs. As a result of the acute renal damage, the patient
      suffered a severe metformin-associated lactic acidosis. The rest of the causes of
      metabolic acidosis with an increased anion gap were ruled out, as well as a
      possible sepsis or rhabdomyolysis. Metformin-associated lactic acidosis is an
      uncommon metabolic condition, but with a high mortality. To reduce the mortality
      of these patients, it is important to make an early diagnosis using the clinical
      records, physical examination, and laboratory tests, with an early resuscitation
      with volume, vasopressors, bicarbonate, and renal replacement therapy.

PMID- 22609264
TI  - [Acute abdomen and hyperparathyroidism: a description of a case].
AB  - Hypercalcaemia secondary to primary hyperparathyroidism may present with an
      insidious clinical picture and involve multiple organs, which may lead to a delay
      in its diagnosis and erroneous therapeutic actions, due to its similarity to
      other different conditions. We describe the case of a patient who was admitted to
      our hospital with the diagnosis of acute abdomen. A laparotomy was performed
      which was negative. The slow post-operative progress and the clinical neurology
      of the patient was resolved after checking for the presence of a significant
      hypercalcaemia secondary to a parathyroid lymph node.

PMID- 22609265
TI  - [Sino-auricular block immediately after cataract surgery. Casualty or
      causality?].

PMID- 22609266
TI  - [Mucormycosis with no previous immune compromise in the resuscitation unit].

PMID- 22609267
TI  - [Incidence of accidental dura mater punctures in a university hospital: a
      prospective observational study].
AB  - OBJECTIVE: Accidental dura mater puncture is a potential complication during
      epidural block, and may be associated with multiple factors. Our objective was to
      determine the prevalence and risk factors of accidental dural puncture in a
      university hospital, evaluating the differences in the number of complications
      during different working hours. MATERIAL AND METHODS: A prospective observational
      study was conducted on all women who requested regional anaesthesia in the
      Epidural Analgesia Unit between 1 January 2009 and 1 January 2011, and who
      fulfilled the inclusion criteria. The technique employed to control labour pains
      was epidural analgesia. RESULTS: A total of 12,480 pregnant women were included.
      The prevalence of accidental dura mater puncture was 0.4% (50 patients). Of
      these, 28% were due to medical residents. More accidental dura mater punctures
      were observed during September and in the afternoon shift. CONCLUSIONS: The
      prevalence of accidental dura mater puncture is similar to other patient series.
      In ours, tiredness or lack of sleep did not influence the incidence of
      complications in analgesia for labour pains in a 24 hour care unit. This may be
      due to the distribution of on-call shifts not exceeding more than 6 hours.

PMID- 22609268
TI  - The role of femA regulating gene on methicillin-resistant Staphylococcus aureus
      clinical isolates.
AB  - OBJECTIVE: The authors investigated the role of femA regulating gene on
      methicillin-resistant Staphylococcus aureus (MRSA). METHODS: High-level MRSA, low
      level MRSA, and methicillin-susceptible Staphylococcus aureus (MSSA) were
      determined by agar diffusion methods. beta-lactamase was then detected by
      nitrocefin and the presence of mecA was determined by PCR. Only beta-lactamase
      negative but mecA-positive isolates were included in further studies. The femA
      gene and its 250 bp upstream sequence were amplified by PCR. Expression levels of
      femA were determined by real-time fluorescent quantitative PCR. The 250 bp
      upstream sequence of femA was labeled by BrightStar Psoralen-Biotin and was
      detected by electrophoretic mobility shift assay (EMSA). RESULTS: The expression
      levels of femA in the three different groups (MSSA, low-level MRSA, and high
      level MRSA) ranged from 3.53*10-3% to 29.91%, 5.54*10-3% to 3.1*102%, and 13.88%
      to 5.50*104%, respectively. EMSA could detect the signal shift in 55 high-level
      MRSA isolates but not in four low-level MRSA and four MSSA strains. CONCLUSION:
      The expression levels of femA in high-level MRSA (non-beta-lactamase-producing)
      were higher than in low-level MRSA and MSSA. The femA regulating gene probably
      lies in the 250 bp upstream sequence in MRSA. High-level expression of femA seems
      to be essential for high-level MRSA.

PMID- 22609269
TI  - Bevacizumab therapy may contribute to irradiation deferral in patients with
      breast cancer and with central nervous system metastases: findings of a case
      series.

PMID- 22609270
TI  - Improving quality, service delivery and patient experience in a musculoskeletal
      service.
AB  - The purpose of this quality improvement initiative was to enhance service
      delivery and patient experience in a musculoskeletal out-patient setting. A cross
      sectional survey, with 6 annual stages, evaluated the musculoskeletal outpatient
      physiotherapy service in a large National Health Service hospital in Southern
      England. The population comprised 1095 patients, referred by medical staff to the
      service from rheumatology, orthopaedics, pain clinic and occupational health
      departments. The individual clinician-initiated strategies for quality
      improvement included: cue cards; reminders; reflections and training. The systems
      changes comprised revised documentation and booking systems. The primary outcome
      was patient experience, measured with the Chartered Society of Physiotherapy's
      standardised 'Patients feedback' questionnaire. Attendance data was a secondary
      outcome. This initiative showed that strategies to motivate individual clinicians
      to change their behaviour were unsuccessful, whereas system-changes resulted in
      32/37 improvements (8 statistically significant) in patient experience.
      Furthermore, the revised systems resulted in a 6% decrease in wasted
      appointments. It is essential that clinical services are evaluated through the
      eyes of their users. This initiative demonstrates the value of service
      evaluations (alongside research) and the importance of patient feedback to show
      how it can drive change and positively impact upon health-care experiences.
      Furthermore, this work has shown that active implementation strategies with
      systems-level changes produced greater improvements in service quality and
      patient experience, than simply encouraging and supporting clinicians to change
      their behaviour.

PMID- 22609272
TI  - Xmab21l3 mediates dorsoventral patterning in Xenopus laevis.
AB  - Specification of the dorsoventral (DV) axis is critical for the subsequent
      differentiation of regional fate in the primary germ layers of the vertebrate
      embryo. We have identified a novel factor that is essential for dorsal
      development in embryos of the frog Xenopus laevis. Misexpression of Xenopus mab21
      like 3 (Xmab21l3) dorsalizes gastrula-stage mesoderm and neurula-stage ectoderm,
      while morpholino-mediated knockdown of Xmab21l3 inhibits dorsal differentiation
      of these embryonic germ layers. Xmab21l3 is a member of a chordate-specific
      subclass of a recently characterized gene family, all members of which contain a
      conserved, but as yet ill-defined, Mab21 domain. Our studies suggest that
      Xmab21l3 functions to repress ventralizing activity in the early vertebrate
      embryo, via regulation of BMP/Smad and Ras/ERK signaling.

PMID- 22609273
TI  - fMRI-activation during drawing a naturalistic or sketchy portrait.
AB  - Neural processes for naturalistic drawing might be discerned into object
      recognition and analysis, attention processes guiding eye hand interaction,
      encoding of visual features in an allocentric reference frame, a transfer into
      the motor command and precise motor guidance with tight sensorimotor feedback.
      Cerebral representations in a real life paradigm during naturalistic drawing have
      sparsely been investigated. Using a functional Magnetic Resonance Imaging (fMRI)
      paradigm we measured 20 naive subjects during drawing a portrait from a frontal
      face presented as a photograph. Participants were asked to draw the portrait in
      either a naturalistic or a sketchy characteristic way. Tracing the contours of
      the face with a pencil or passive viewing of the face served as control
      conditions. Compared to passive viewing, naturalistic and sketchy drawing
      recruited predominantly the dorsal visual pathway, somatosensory and motor areas
      and bilateral BA 44. The right occipital lobe, middle temporal (MT) and the
      fusiform face area were increasingly active during drawing compared to passive
      viewing as well. Compared to tracing with a pencil, both drawing tasks
      increasingly involved the bilateral precuneus together with the cuneus and right
      inferior temporal lobe. Overall, our study identified cerebral areas
      characteristic for previously proposed aspects of drawing: face perception and
      analysis (fusiform gyrus and higher visual areas), encoding and retrieval of
      locations in an allocentric reference frame (precuneus), and continuous feedback
      processes during motor output (parietal sulcus, cerebellar hemisphere).

PMID- 22609274
TI  - The influence of triamcinolone on endostatin-like proteins in oxygen-induced
      retinopathy of prematurity.
AB  - In the murine model of oxygen-induced retinopathy of prematurity, early treatment
      (right after oxygen exposure) with triamcinolone reduced neovascularization and
      subsequently endostatin presence. Late treatment (3 days after oxygen exposure)
      limited pathological vascular sprouting, not interfering with normal
      vascularization of the retina. The effects remained unilateral in the treated
      eyes.

PMID- 22609271
TI  - Why do bacteria use so many enzymes to scavenge hydrogen peroxide?
AB  - Hydrogen peroxide (H(2)O(2)) is continuously formed by the autoxidation of redox
      enzymes in aerobic cells, and it also enters from the environment, where it can
      be generated both by chemical processes and by the deliberate actions of
      competing organisms. Because H(2)O(2) is acutely toxic, bacteria elaborate
      scavenging enzymes to keep its intracellular concentration at nanomolar levels.
      Mutants that lack such enzymes grow poorly, suffer from high rates of
      mutagenesis, or even die. In order to understand how bacteria cope with oxidative
      stress, it is important to identify the key enzymes involved in H(2)O(2)
      degradation. Catalases and NADH peroxidase (Ahp) are primary scavengers in many
      bacteria, and their activities and physiological impacts have been unambiguously
      demonstrated through phenotypic analysis and through direct measurements of
      H(2)O(2) clearance in vivo. Yet a wide variety of additional enzymes have been
      proposed to serve similar roles: thiol peroxidase, bacterioferritin comigratory
      protein, glutathione peroxidase, cytochrome c peroxidase, and rubrerythrins. Each
      of these enzymes can degrade H(2)O(2) in vitro, but their contributions in vivo
      remain unclear. In this review we examine the genetic, genomic, regulatory, and
      biochemical evidence that each of these is a bonafide scavenger of H(2)O(2) in
      the cell. We also consider possible reasons that bacteria might require multiple
      enzymes to catalyze this process, including differences in substrate specificity,
      compartmentalization, cofactor requirements, kinetic optima, and enzyme
      stability. It is hoped that the resolution of these issues will lead to an
      understanding of stress resistance that is more accurate and perceptive.

PMID- 22609275
TI  - High levels of gene expression in the hepatocytes of adult mice, neonatal mice
      and tree shrews via retro-orbital sinus hydrodynamic injections of naked plasmid
      DNA.
AB  - Hydrodynamic-based gene delivery has emerged as an efficient and simple method
      for the intracellular transfection of naked plasmid DNA (pDNA) in vivo. In this
      system, a hydrodynamic injection via the tail vein is the most effective non
      viral method of liver-targeted gene delivery. However, this injection is often
      technically challenging when used in animals whose tail veins are difficult to
      visualize or too small to operate on. To overcome this limitation, an alternative
      in vivo gene delivery method, the rapid injection of large volume of pDNA
      solution through retro-orbital sinus, was established. Using this technique, we
      successfully delivered pDNA to the tissue of adult mice, neonatal mice and tree
      shrews. The efficient expression of exogenous genes was specifically detected in
      the liver of test animals treated with this gene delivery method. This study
      demonstrates for the first time that the hydrodynamic gene delivery via the retro
      orbital sinus can not only reach the same transgene efficiency as a tradition
      hydrodynamic-based intravascular injection but also be used in animals that are
      difficult to inject via the tail vein. This method could open up new areas in
      gene function studies and gene therapy disease treatment.

PMID- 22609276
TI  - Beta-eleostearic acid induce apoptosis in T24 human bladder cancer cells through
      reactive oxygen species (ROS)-mediated pathway.
AB  - Beta-eleostearic acid (beta-ESA, 9E11E13E-18:3), a linolenic acid isomer with a
      conjugated triene system, is a natural and biologically active compound. Herein,
      we investigated effects of beta-eleostearic acid on T24 human bladder cancer
      cells. In this study, results showed that beta-eleostearic acid had strong
      cytotoxicity to induce cell apoptosis, which was mediated by reactive oxygen
      species (ROS) in T24 cells. The cell viability assay results showed that
      incubation with beta-eleostearic acid concentrations of 10-80MUmol/L caused a
      dose- and time-dependent decrease of T24 cell viability, and the IC(50) value was
      21.2MUmol/L at 24h and 13.1MUmol/L at 48h. Annexin V/PI double staining was used
      to assess apoptosis with flow cytometry. Treatment with beta-eleostearic acid
      caused massive ROS accumulation and GSH decrease, which lead to activation of
      caspase-3 and down-regulation of Bcl-2 indicating induction of apoptosis.
      Subsequently, N-acetyl-l-cysteine (NAC) and PEG-catalase effectively blocked the
      ROS elevated effect of beta-eleostearic acid, which suggested that beta
      eleostearic acid-induced apoptosis involved ROS generated. Additionally, we found
      that treating T24 cells with beta-eleostearic acid induced activation of
      PPARgamma. A PPARgamma-activated protein kinase inhibitor was able to partially
      abrogate the effects of beta-eleostearic acid. These results suggested that beta
      eleostearic acid can induce T24 cells apoptosis via a ROS-mediated pathway which
      may be involved PPARgamma activation.

PMID- 22609277
TI  - Pregnane X receptor as a target for treatment of inflammatory bowel disorders.
AB  - Pregnane X receptor (PXR; NR1I2), a member of the nuclear receptor superfamily,
      has a major role in the induction of genes involved in drug transport and
      metabolism. Recent studies in mice have provided insight into a novel function
      for PXR in inflammatory bowel disease (IBD). The mechanism of the protective
      effect of PXR activation on IBD is not fully established, but is due in part to
      the attenuation of nuclear factor (NF)-kappaB signaling that results in lower
      expression of proinflammatory cytokines. Recent clinical trials with the
      antibiotic rifaximin, a PXR agonist in the gastrointestinal system, have revealed
      its potential therapeutic value in the treatment of intestinal inflammation in
      humans. Thus, PXR may be a novel target for IBD therapy.

PMID- 22609279
TI  - Sec13 safeguards the integrity of the endoplasmic reticulum and organogenesis of
      the digestive system in zebrafish.
AB  - The Sec13-Sec31 heterotetramer serves as the outer coat in the COPII complex,
      which mediates protein trafficking from the endoplasmic reticulum (ER) to the
      Golgi apparatus. Although it has been studied in depth in yeast and cultured
      cells, the role of COPII in organogenesis in a multicellular organism has not. We
      report here that a zebrafish sec13(sq198) mutant, which exhibits a phenotype of
      hypoplastic digestive organs, has a mutation in the sec13 gene. The mutant gene
      encodes a carboxyl-terminus-truncated Sec13 that loses its affinity to Sec31a,
      which leads to disintegration of the ER structure in various differentiated cells
      in sec13(sq198), including chondrocytes, intestinal epithelial cells and
      hepatocytes. Disruption of the ER structure activates an unfolded protein
      response that eventually causes the cells to undergo cell-cycle arrest and cell
      apoptosis, which arrest the growth of developing digestive organs in the mutant.
      Our data provide the first direct genetic evidence that COPII function is
      essential for the organogenesis of the digestive system.

PMID- 22609280
TI  - A pseudotumoral presentation of pancreatic tuberculosis.

PMID- 22609278
TI  - Pushing the envelope of retinal ganglion cell genesis: context dependent function
      of Math5 (Atoh7).
AB  - The basic-helix-loop helix factor Math5 (Atoh7) is required for retinal ganglion
      cell (RGC) development. However, only 10% of Math5-expressing cells adopt the RGC
      fate, and most become photoreceptors. In principle, Math5 may actively bias
      progenitors towards RGC fate or passively confer competence to respond to
      instructive factors. To distinguish these mechanisms, we misexpressed Math5 in a
      wide population of precursors using a Crx BAC or 2.4 kb promoter, and followed
      cell fates with Cre recombinase. In mice, the Crx cone-rod homeobox gene and
      Math5 are expressed shortly after cell cycle exit, in temporally distinct, but
      overlapping populations of neurogenic cells that give rise to 85% and 3% of the
      adult retina, respectively. The Crx>Math5 transgenes did not stimulate RGC fate
      or alter the timing of RGC births. Likewise, retroviral Math5 overexpression in
      retinal explants did not bias progenitors towards the RGC fate or induce cell
      cycle exit. The Crx>Math5 transgene did reduce the abundance of early-born
      (E15.5) photoreceptors two-fold, suggesting a limited cell fate shift.
      Nonetheless, retinal histology was grossly normal, despite widespread persistent
      Math5 expression. In an RGC-deficient (Math5 knockout) environment, Crx>Math5
      partially rescued RGC and optic nerve development, but the temporal envelope of
      RGC births was not extended. The number of early-born RGCs (before E13) remained
      very low, and this was correlated with axon pathfinding defects and cell death.
      Together, these results suggest that Math5 is not sufficient to stimulate RGC
      fate. Our findings highlight the robust homeostatic mechanisms, and role of
      pioneering neurons in RGC development.

PMID- 22609281
TI  - Inhibition of lipid peroxidation and protein oxidation by endogenous and
      exogenous antioxidants in rat brain microsomes in vitro.
AB  - Reactive oxygen and reactive nitrogen species oxidize and nitrate DNA, lipid and
      proteins thus leading to neuronal death. Both endogenous and dietary antioxidants
      were shown to afford neuroprotection either by scavenging free radicals or
      inducing antioxidant enzymes. That said, the differential contribution of
      endogenous versus nutritional antioxidants to prevent neurodegeneration is still
      debated. In this study the free radical scavenging activity of two endogenous
      antioxidants, such as bilirubin and its precursor biliverdin, was compared with
      that of the dietary antioxidant alpha-tocopherol in rat brain microsomes exposed
      to peroxyl radical or peroxynitrite in vitro. Bilirubin and biliverdin (1-200
      MUM) inhibited both peroxyl radical- and peroxynitrite-dependent lipid
      peroxidation with a greater potency and efficacy than alpha-tocopherol. However,
      both BV and BR displayed greater potency and efficacy in preventing peroxynitrite
      than peroxyl radical-induced lipid peroxidation. The greater antioxidant effect
      of both bilirubin and biliverdin than alpha-tocopherol was also confirmed against
      peroxyl radical- and peroxynitrite-induced protein oxidation. In conclusion, both
      bilirubin and biliverdin exhibited a greater antioxidant activity than alpha
      tocopherol in preventing oxidative stress damage in rat brain.

PMID- 22609282
TI  - DJ-1 deficiency perturbs microtubule dynamics and impairs striatal neurite
      outgrowth.
AB  - Parkinson's disease (PD) is a common neurodegenerative disease characterized by
      the selective loss of the dopaminergic (DA) neurons in substantia nigra. The
      degeneration leads to decreased levels of DA in striatum and causes uncontrolled
      firing of innervated medium spiny neurons (MSNs), thus preventing the patient to
      act smoothly. Gene-specific deficient mouse models for the recessive forms of PD
      were generated in the past decade, although most failed to exhibit degeneration
      of DA neurons or decreased DA level, as evidenced in PD patients. Here by using
      DJ-1-knockdown neuroblastoma SH-SY5Y cells and Neuro-2a cells as well as DJ-1
      deficient mice, we found DJ-1 deficiency could downregulate beta-tubulin III via
      a hypoxia-inducible factor 1alpha (HIF-1alpha) pathway, and, correspondingly, we
      observed reduced microtubule dynamics. With Golgi-Cox impregnation, we also
      observed declined dendritic complexity and the loss of dendritic spines in
      striatal MSNs of DJ-1-deficient mice. Our results revealed a novel role of DJ-1
      in the regulation of microtubule dynamics and suggested that striatal impairments
      may also play an important role as loss of DA neurons in the pathogenesis of PD.

PMID- 22609283
TI  - Phase behavior and oral bioavailability of amorphous Curcumin.
AB  - Amorphous form has been used as a means to improve aqueous solubility and oral
      bioavailability of poorly water soluble drugs. The objective of present study was
      to characterize thermodynamic and kinetic parameters of amorphous form of
      Curcumin (CRM-A). CRM-A was found to be a good glass former with glass transition
      temperature (T(g)) of 342.64K and critical cooling rate below 1K/min. CRM-A had a
      moderate tendency of crystallization and exhibited Kauzmann temperature (T(KS))
      of 294.23 K. CRM-A was found to be fragile in nature as determined by T(m)/T(g)
      (1.32), C(p)(1 iq):C(p)(glass) (1.22), strength parameter (D<10), fragility index
      (m>75), T(K)/T(g) (0.85), and T(g)-T(K) (48.41). Theoretically predicted aqueous
      solubility advantage of 43.15-folds, was reduced to 17-folds under practical
      conditions. This reduction in solubility was attributed to water induced
      devitrification, as evident through PXRD and SEM analysis. Further, oral
      bioavailability study of CRM-A was undertaken to investigate bioavailability
      benefits, if any. C(max) was improved by 1.97-folds (statistically significant
      difference over control). However, oral bioavailability (AUC(0-)(infinity)) was
      improved by 1.45-folds (statistically non significant difference over control).
      These observations pointed towards role of rapid devitrification of CRM-A in GIT
      milieu, thus limiting its oral bioavailability advantage.

PMID- 22609284
TI  - Why biosynthetic genes for chemical defense compounds cluster.
AB  - In plants, the genomic clustering of non-homologous genes for the biosynthesis of
      chemical defense compounds is an emerging theme. Gene clustering is also observed
      for polymorphic sexual traits under balancing selection, and examples in plants
      are self-incompatibility and floral dimorphy. The chemical defense pathways
      organized as gene clusters are self-contained biosynthetic modules under opposing
      selection pressures and adaptive polymorphisms, often the presence or absence of
      a functional pathway, are observed in nature. We propose that these antagonistic
      selection pressures favor closer physical linkage between beneficially
      interacting alleles as the resulting reduction in recombination maintains a
      larger fraction of the fitter genotypes. Gene clusters promote the stable
      inheritance of functional chemical defense pathways in the dynamic ecological
      context of natural populations.

PMID- 22609285
TI  - Molecular evolution and emergence of avian gammacoronaviruses.
AB  - Coronaviruses, which are single stranded, positive sense RNA viruses, are
      responsible for a wide variety of existing and emerging diseases in humans and
      other animals. The gammacoronaviruses primarily infect avian hosts. Within this
      genus of coronaviruses, the avian coronavirus infectious bronchitis virus (IBV)
      causes a highly infectious upper-respiratory tract disease in commercial poultry.
      IBV shows rapid evolution in chickens, frequently producing new antigenic types,
      which adds to the multiple serotypes of the virus that do not cross protect.
      Rapid evolution in IBV is facilitated by strong selection, large population sizes
      and high genetic diversity within hosts, and transmission bottlenecks between
      hosts. Genetic diversity within a host arises primarily by mutation, which
      includes substitutions, insertions and deletions. Mutations are caused both by
      the high error rate, and limited proof reading capability, of the viral RNA
      dependent RNA-polymerase, and by recombination. Recombination also generates new
      haplotype diversity by recombining existing variants. Rapid evolution of avian
      coronavirus IBV makes this virus extremely difficult to diagnose and control, but
      also makes it an excellent model system to study viral genetic diversity and the
      mechanisms behind the emergence of coronaviruses in their natural host.

PMID- 22609286
TI  - Midterm follow-up of transjugular intrahepatic portosystemic shunts using
      polytetrafluoroethylene endografts in children.
AB  - PURPOSE: To report the initial experience of a pediatric center's use of expanded
      polytetrafluoroethylene (ePTFE) endografts for the creation of transjugular
      intrahepatic portosystemic shunts (TIPSs) in children. MATERIALS AND METHODS:
      Twelve consecutive patients had a TIPS created, all with ePTFE endografts. Nine
      were children younger than 18 years of age: one infant (age 18 mo) and eight
      adolescent children with a median age of 14 years, 3 months (range, 10 y, 1 mo,
      to 17 y, 2 mo). All had gastric or esophageal varices. Acute variceal bleeding
      was the primary indication in four of nine cases (44%). Mean follow-up was 20
      months (range, 4 d to 32 mo). RESULTS: Technical success rate was 100%. Seven
      TIPSs (78%) were created with a 10-mm-diameter endograft and two (22%) were
      created with an 8-mm-diameter endograft. Mean portosystemic gradient was reduced
      from 15.9 mm Hg to 5.8 mm Hg after TIPS creation. The devices were not dilated to
      their nominal diameter in seven of nine cases (78%). There were no major
      complications or mortalities associated with TIPS creation. There was one minor
      complication during follow-up in which a child developed progressively increasing
      lethargy. Primary patency rate by ultrasound during follow-up was 100%. There
      were no shunt dysfunctions or repeat interventions required, and no clinical
      recurrences. One child received a liver transplant 4 days after TIPS creation.
      CONCLUSIONS: TIPSs can be created in children with the use of ePTFE endografts
      with an excellent midterm primary patency rate and a low complication rate.

PMID- 22609287
TI  - Pulsed high-intensity-focused US and tissue plasminogen activator (TPA) versus
      TPA alone for thrombolysis of occluded bypass graft in swine.
AB  - PURPOSE: Prosthetic arteriovenous or arterial-arterial bypass grafts can
      thrombose and be resistant to revascularization. A thrombosed bypass graft model
      was created to evaluate the potential therapeutic enhancement and safety profile
      of pulsed high-intensity-focused ultrasound (pHIFU) on pharmaceutical
      thrombolysis. MATERIALS AND METHODS: In swine, a right carotid-carotid expanded
      polytetrafluoroethylene bypass graft was surgically constructed, containing a 40%
      stenosis at its distal end to induce graft thrombosis. The revascularization
      procedure was performed 7 days after surgery. After model development and dose
      response experiments (n = 11), two cohorts were studied: pHIFU with tissue
      plasminogen activator (TPA; n = 4) and sham pHIFU with TPA (n = 3). The
      experiments were identical in both groups except no energy was delivered in the
      sham pHIFU group. Serial angiograms were obtained in all cases. The area of graft
      opacified by contrast medium on angiograms was quantified with digital image
      processing software. A blinded reviewer calculated the change in the graft area
      opacified by contrast medium and expressed it as a percentage, representing
      percentage of thrombolysis. RESULTS: Combining pHIFU with 0.5 mg of TPA resulted
      in a 52% +/- 4% increase in thrombolysis on angiograms obtained at 30 minutes,
      compared with a 9% +/- 14% increase with sham pHIFU and 0.5 mg TPA (P = .003).
      Histopathologic examination demonstrated no differences between the groups.
      CONCLUSIONS: Thrombolysis of occluded bypass grafts was significantly increased
      when combining pHIFU and TPA versus sham pHIFU and TPA. These results suggest
      that application of pHIFU may augment thrombolysis with a reduced time and dose.

PMID- 22609288
TI  - Aortic branch artery pseudoaneurysms accompanying aortic dissection. Part III:
      natural history.
AB  - PURPOSE: To document the natural history of branch artery pseudoaneurysms (BAPs),
      which are sequelae of aortic dissection with false lumen thrombosis that have
      been distinguished anatomically from penetrating ulcers. MATERIALS AND METHODS:
      Serial computed tomography (CT) scans in 50 patients with at least two CT scans
      greater than 1 month apart were retrospectively studied. Mean follow-up was 29
      months, with longitudinal analyses of 119 BAPs. Changes in BAPs, false lumen
      thrombosis, and aortic diameter were assessed. RESULTS: No patient had an aortic
      rupture or other poor outcome. All BAPs eventually disappeared (ie, thrombosed),
      with 50% thrombosed within 18 months. Aortas were ectatic, with a mean diameter
      of 36 mm. There was no statistically significant change in total aortic
      diameters; however, there was a significant increase in true lumen diameters (P <
      .0001) and a significant decrease in false lumen thickness (P < .0001) at the
      level of the BAP over time (mean 50% reduction in maximum thickness of thrombosed
      false lumen). There were no significant associations between BAP thrombosis and
      vertebral level, presence of more than one BAP, presence of branch artery in
      communication with the BAP, history of smoking, diabetes mellitus or
      hypertension, or treatment with beta-blockers, other antihypertensive medication,
      statins, or anticoagulation therapy. After controlling for other variables, BAPs
      were less likely to thrombose if an ulcerlike projection was present (P = .003),
      in men (P = .02), in subjects with hypertension (P = .04), and in older patients
      (P = .05). CONCLUSIONS: Most BAPs spontaneously thrombose, and associated
      intramural hematoma regresses/disappears. Isolated BAPs were not associated with
      poor clinical outcomes.

PMID- 22609289
TI  - Soft tissue bleeding associated with antithrombotic treatment: technical and
      clinical outcomes after transcatheter embolization.
AB  - PURPOSE: To assess retrospectively technical and clinical outcomes after
      transcatheter embolization in patients presenting with soft tissue bleeding
      associated with antithrombotic therapy and to determine factors potentially
      affecting the clinical outcomes after embolization. MATERIALS AND METHODS: There
      were 42 patients who underwent embolization for soft tissue bleeding associated
      with antithrombotic therapy. Principal clinical symptoms were hemodynamic shock
      (n = 21), abdominal pain (n = 9), back pain (n = 7), and buttock or thigh pain (n
      = 5). Ultrasound or computed tomography (CT) or both were performed in 40
      patients (95%); 2 patients (5%) were immediately referred for angiography.
      Several laboratory and radiographic factors were analyzed to determine if any
      influenced the clinical outcome. RESULTS: A hematoma was identified in the
      anterior abdominal wall (n = 18 [43%]), in the retroperitoneum (n = 18 [43%]), or
      in the thigh or gluteal region (n = 6 [14%]). Embolization was successful in all
      patients; early recurrent bleeding with a fatal outcome was recorded in one
      patient (2%). In nine patients (22%), secondary surgical drainage of the hematoma
      was performed to manage a compartment syndrome. During follow-up (mean, 37.9
      months; range, 0.03-85.28 months), 11 patients (26%) died; death was related to
      the bleeding in 6 patients (14%). Both activated partial thromboplastin time
      (aPTT) and prothrombin time (PT) were correlated with hematoma size. Prolonged
      aPTT before embolization was associated with a higher risk of bleeding-related
      mortality (P = .04). CONCLUSIONS: Transcatheter embolization was very effective
      in stopping soft tissue bleeding associated with antithrombotic therapy. However,
      there was still considerable morbidity and mortality after successful
      embolization. aPTT prolongation emerged as a risk factor for bleeding-related
      deaths.

PMID- 22609290
TI  - Efficacy of transarterial chemoembolization for hepatocellular carcinoma in
      interlobar watershed zone of liver: comparison of unilateral and bilateral
      chemoembolization.
AB  - PURPOSE: To evaluate the treatment efficacy of unilateral versus bilateral
      transarterial chemoembolization for hepatocellular carcinoma (HCC) based on
      whether the tumor is located across the Cantlie line within the watershed zone of
      the liver. MATERIALS AND METHODS: Seventy-seven patients with 87 HCCs located in
      the watershed zone who underwent complete chemoembolization (unilateral, n = 57
      [74%]; bilateral, n = 20 [26%]) were included. Tumors located in the watershed
      zone were further divided into two groups: tumors across the Cantlie line (type
      A) and tumors not across the line (type B). Comparison of treatment outcomes of
      unilateral or bilateral chemoembolization for the two groups was performed. The
      tumor viability (ie, presence of viable component or tumor progression) and
      position of the viable component on follow-up computed tomography was recorded.
      RESULTS: Tumor viability rates for type A tumors in the unilateral and bilateral
      chemoembolization groups were 52.2% and 11.1%, respectively; for type B tumors,
      they were 23.7% and 11.8%, respectively. The tumor viability rate of type A
      tumors was significantly higher in the unilateral chemoembolization group than in
      the bilateral chemoembolization group (P = .05), but there was no significant
      difference for type B tumors (P > .05). CONCLUSIONS: The tumor viability rate of
      HCC tumors across the Cantlie line was higher with unilateral chemoembolization
      group than with bilateral chemoembolization. In patients with HCC across the
      Cantlie line, embolization of bilateral hepatic arteries may achieve better
      treatment efficacy.

PMID- 22609291
TI  - Evaluation and treatment of suspected type II endoleaks in patients with
      enlarging abdominal aortic aneurysms.
AB  - PURPOSE: To evaluate angiographic diagnosis and embolotherapy of patients with
      enlarging abdominal aortic aneurysms and computed tomographic (CT) diagnosis of
      type II endoleak. MATERIALS AND METHODS: A retrospective review was performed of
      all patients referred to a single vascular and interventional radiology section
      from January 1, 2003, to June 1, 2011, with a diagnosis of enlarging aneurysm and
      type II endoleak. Twenty-five patients underwent 40 procedures between 12 and 82
      months after endograft insertion (mean, 48 mo) for diagnosis and/or treatment of
      endoleaks. RESULTS: Type II endoleaks were treated with cyanoacrylate, coils, and
      ethylene vinyl alcohol copolymer in 16 patients. Technical success rate was 88%
      (14 of 16 patients) and clinical success rate was 100% (16 of 16 patients).
      Aneurysm growth was arrested in all cases over a mean follow-up of 27.5 months
      (range, 6-88 mo). Endoleaks in nine patients were misclassified on CT; two had
      type I endoleaks and seven had type III endoleaks. Four of the nine patients (two
      type I endoleaks and two type III endoleaks) were correctly classified after
      initial angiography. The other five type III endoleaks were correctly classified
      on CT after coil embolization of the inferior mesenteric artery. Direct
      embolization was performed via sac puncture with ethylene vinyl alcohol copolymer
      in two of the latter five patients and eliminated endoleaks in both. CONCLUSIONS:
      Aneurysm growth caused by type II endoleaks was arrested by embolization. CT
      misclassification occurred relatively commonly; type III endoleaks purported to
      be type II endoleaks were found in 28% of patients (seven of 25).

PMID- 22609292
TI  - Prognostic value of 18f-fluorodeoxyglucose positron emission tomography-computed
      tomography in predicting survival in patients with unresectable metastatic
      melanoma to the liver undergoing yttrium-90 radioembolization.
AB  - PURPOSE: To investigate the prognostic value of (18)F-fluorodeoxyglucose (FDG)
      positron emission tomography-computed tomography (PET-CT) in predicting survival
      in patients with unresectable metastatic melanoma to the liver undergoing yttrium
      90 ((90)Y) radioembolization. MATERIALS AND METHODS: A retrospective review of 12
      patients with unresectable hepatic melanoma metastases (5 patients with cutaneous
      metastases, 7 patients with ocular metastases) who underwent (18)F-FDG PET-CT
      before (90)Y was performed. Metabolically significant tumors, defined as having a
      long-axis diameter >= 1 cm and maximum standardized uptake value (SUV(max)) >=
      2.5, were identified on (18)F-FDG PET-CT. SUV(max), glycolytic activity, and
      volume were determined for each tumor. Overall SUV(max), total tumor glycolytic
      activity (TGA), total metabolic tumor volume (MTV), and metabolic tumor burden
      (MTB) based on percentage of liver involvement (MTV/total liver volume) were
      calculated. Kaplan-Meier method, life-table analysis, and Cox proportional
      hazards model were used for statistical analysis. RESULTS: Median SUV(max) was
      10.9 (range, 4.6-15.3), median TGA was 377.0 SUV/cm(3) (range, 53.6-20,393.4
      SUV/cm(3)), median MTV was 85.4 cm(3) (range, 11.5-2,504.1 cm(3)), and median MTB
      was 5.5% (range, 0.1%-54.0%). MTB was found to be a significant negative
      prognostic marker of survival on univariate (P = .020) and multivariate (P =
      .018) analyses accounting for age and duration from metastatic diagnosis to first
      (90)Y treatment. A 60th percentile MTB of 7.0% (hazard ratio, 5.704; P = .040)
      was a statistically significant cutoff. Median survivals from first (90)Y
      treatment in patients with MTB < 7.0% and >= 7.0% were 10.8 months (95%
      confidence interval [CI], 6.8-14.8) and 4.7 months (95% CI, 1.6-7.8),
      respectively. SUV(max) (P = .422), TGA (P = .064), and MTV (P = .065) were not
      found to be statistically significant. CONCLUSIONS: MTB based on (18)F-FDG PET-CT
      performed before treatment was found to be a negative prognostic factor for
      patient survival after (90)Y radioembolization for unresectable metastatic
      melanoma to liver.

PMID- 22609293
TI  - Pathology: a pictorial review. A selected atlas of paediatric liver pathology.
AB  - Indications for liver biopsy in children are often specific to this age group,
      especially in young children for the diagnosis of cholestasis. Since liver
      biopsies are quite unfrequent in the children population and concern rare but
      various diseases, it is recommended to entrust the analysis to a specialized
      liver pathologist, in a laboratory where cryoconservation, specific immuno
      stainings, enzymatic studies, and electron microscopy can be performed. Histology
      is complementary to other methods for the diagnosis, and is valuable for the
      evaluation of the prognosis, especially the staging of fibrosis and the grading
      of inflammatory diseases. In cases of co-morbidity or difficult differential
      diagnosis, histology can also be of great value. For metabolic disorders, the
      liver tissue can also be used for enzyme detection or evaluation of iron or
      copper overload. Biopsy is also a key element in the management after liver
      transplantation. The microscopic images shown here are representative of the most
      frequent liver diseases in childhood and illustrate the data outlined during the
      conference.

PMID- 22609294
TI  - Neonatal jaundice.
AB  - Neonatal jaundice lasting greater than 2 weeks should be investigated. Pale
      stools and dark or yellow urine are evidence of liver disease, which should be
      urgently investigated. The neonatal hepatitis syndrome has many causes, and a
      structured approach to investigation is mandatory. It should be possible to
      confirm or exclude biliary atresia within one week, so that definitive surgery is
      not delayed unnecessarily. Babies with the neonatal hepatitis syndrome should
      have vigorous fat-soluble vitamin supplementation, including parenteral vitamin K
      if coagulation is abnormal. The prognosis for infants with idiopathic neonatal
      hepatitis and multifactorial cholestasis is excellent.

PMID- 22609295
TI  - Progressive familial intrahepatic cholestasis and inborn errors of bile acid
      synthesis.
AB  - Progressive familial intrahepatic cholestasis (PFIC), types 1, 2 and 3, are due
      to defects in genes involved in bile secretion (FIC1, BSEP, MDR3). PFIC and
      inborn errors of bile acid synthesis (IEBAS) often present in infancy with
      cholestasis. The distinctive feature of PFIC 1 and 2 and IEBAS is a normal level
      of GGT, while IEBAS are suspected in patients with low plasma bile acids
      concentration. Molecular testing, urinary bile acid analysis (IEBAS), liver
      biopsy and immuno-staining are used for the diagnosis. Some patients with PFIC
      can be successfully treated with ursodeoxycholic acid or partial external biliary
      diversion. IEBAS is treated with cholic acid. Liver transplantation is required
      for cirrhosis with liver failure. Hepatocarcinoma has been reported in PFIC2.

PMID- 22609296
TI  - Biliary atresia.
AB  - Biliary atresia is an obliterative cholangiopathy with progressive hepatobiliary
      disease, starting from the perinatal period. With a frequency of 1/15-18,000 live
      births, biliary atresia is the commonest cause of life-threatening liver disease
      in infants, and fatal if untreated. Prognosis is poor, unless early diagnosis is
      followed by surgical treatment. Clinical aspect, liver function tests,
      scintigraphy, histology, and increasingly, ultrasound techniques and endoscopic
      retrograde cholangiography are being used to discriminate other causes of
      neonatal cholestasis. Ten-year survival of children with biliary atresia,
      including those transplanted for end-stage liver disease, is up to 90%. Prognosis
      and outcome are largely dependent on early diagnosis and expert surgical
      management.

PMID- 22609297
TI  - Hepatic fibrosis in paediatric liver disease.
AB  - Liver fibrosis is the common endpoint of chronic liver disease of variable
      aetiology. Liver injury induces excess deposition of extracellular matrix via
      inflammatory pathways, which in turn results in distortion of the vascular liver
      architecture. The two features combine to cause portal hypertension and reduced
      hepatocellular function. Diagnosis of liver fibrosis is made by liver biopsy, but
      non invasive tests like serological markers or elastographic methods are
      increasingly being recognized as useful tools in the diagnosis of fibrosis.
      Treatment options that exceed the treatment of the underlying liver disease are
      still largely experimental.

PMID- 22609298
TI  - Altered synaptic transmission in the hippocampus of transgenic mice with enhanced
      central nervous systems expression of interleukin-6.
AB  - Elevated levels of the inflammatory cytokine interleukin-6 (IL-6) occur in a
      number of CNS disorders. However, little is known about how this condition
      affects CNS neuronal function. Transgenic mice that express elevated levels of IL
      6 in the CNS show cognitive changes, increased propensity for hippocampal
      seizures and reduced number of inhibitory interneurons, suggesting that elevated
      levels of IL-6 can cause neuroadaptive changes that alter hippocampal function.
      To identify these neuroadaptive changes, we measured the levels of protein
      expression using Western blot analysis and synaptic function using field
      potential recordings in hippocampus from IL-6 transgenic mice (IL-6 tg) and their
      non-transgenic (non-tg) littermates. Western blot analysis showed enhanced levels
      of the GFAP and STAT3 in the IL-6 tg hippocampus compared with the non-tg
      hippocampus, but no difference for several other proteins. Field potential
      recordings of synaptic transmission at the Schaffer collateral to CA1 synapse
      showed enhanced dendritic excitatory postsynaptic potentials and somatic
      population spikes in the CA1 region of hippocampal slices from IL-6 tg mice
      compared with slices from non-tg littermate controls. No differences were
      observed for several forms of short-term and long-term synaptic plasticity
      between hippocampal slices from IL-6 tg and non-tg mice. These results
      demonstrate that elevated levels of IL-6 can alter mechanisms involved in the
      excitability of hippocampal neurons and synapses, an effect consistent with
      recent evidence indicating that elevated production of IL-6 plays an important
      role in conditions associated with seizure activity and in other impairments
      observed in CNS disorders with a neuroinflammatory component.

PMID- 22609299
TI  - Spinal cord injury-functional index: item banks to measure physical functioning
      in individuals with spinal cord injury.
AB  - OBJECTIVES: To develop a comprehensive set of patient-reported items to assess
      multiple aspects of physical functioning relevant to the lives of people with
      spinal cord injury (SCI), and to evaluate the underlying structure of physical
      functioning. DESIGN: Cross-sectional. SETTING: Inpatient and community.
      PARTICIPANTS: Item pools of physical functioning were developed, refined, and
      field tested in a large sample of individuals (N=855) with traumatic SCI
      stratified by diagnosis, severity, and time since injury. INTERVENTIONS: None.
      MAIN OUTCOME MEASURE: Spinal Cord Injury-Functional Index (SCI-FI) measurement
      system. RESULTS: Confirmatory factor analysis (CFA) indicated that a 5-factor
      model, including basic mobility, ambulation, wheelchair mobility, self-care, and
      fine motor function, had the best model fit and was most closely aligned
      conceptually with feedback received from individuals with SCI and SCI clinicians.
      When just the items making up basic mobility were tested in CFA, the fit
      statistics indicated strong support for a unidimensional model. Similar results
      were demonstrated for each of the other 4 factors, indicating unidimensional
      models. CONCLUSIONS: Though unidimensional or 2-factor (mobility and upper
      extremity) models of physical functioning make up outcomes measures in the
      general population, the underlying structure of physical function in SCI is more
      complex. A 5-factor solution allows for comprehensive assessment of key domain
      areas of physical functioning. These results informed the structure and
      development of the SCI-FI measurement system of physical functioning.

PMID- 22609300
TI  - Effect of aquatic exercise training on fatigue and health-related quality of life
      in patients with multiple sclerosis.
AB  - OBJECTIVE: To examine the effectiveness of aquatic exercise training on fatigue
      and health-related quality of life (HRQOL) in women with multiple sclerosis (MS).
      DESIGN: Randomized controlled trial, 4-week and 8-week follow-up. SETTING:
      Referral center of a multiple sclerosis society. PARTICIPANTS: Women (N=32)
      diagnosed with relapsing-remitting MS (mean age +/- SD, 32.6+/-8.0y) were
      recruited into this study. After undergoing baseline testing by a neurologist,
      participants were randomly assigned to either an intervention (aquatic exercise)
      or a control group. INTERVENTIONS: The intervention consisted of 8 weeks
      supervised aquatic exercise in a swimming pool (3 times a week, each session
      lasting 60min). MAIN OUTCOME MEASURES: At baseline, 4 weeks, and 8 weeks, fatigue
      and HRQOL were assessed by a blind assessor using the Modified Fatigue Impact
      Scale and the Multiple Sclerosis Quality of Life-54 questionnaire, respectively.
      A mixed-model approach to repeated-measures analysis of variance was used to
      detect within- and between-subject effects. RESULTS: Findings are based on 21
      patients (10 from the exercise group and 11 from the control group) who had data
      available on outcomes. There was no significant difference between the 2 groups
      at the baseline. Patients in the aquatic exercise group showed significant
      improvements in fatigue and subscores of HRQOL after 4 and 8 weeks compared with
      the control group. Results obtained from the intention-to-treat analysis were
      consistent with those of per-protocol analysis. CONCLUSIONS: The findings suggest
      that aquatic exercise training can effectively improve fatigue and HRQOL of
      patients with MS and should be considered in the management of this relatively
      common public health problem.

PMID- 22609301
TI  - The role of mitochondria in cellular iron-sulfur protein biogenesis and iron
      metabolism.
AB  - Mitochondria play a key role in iron metabolism in that they synthesize heme,
      assemble iron-sulfur (Fe/S) proteins, and participate in cellular iron
      regulation. Here, we review the latter two topics and their intimate connection.
      The mitochondrial Fe/S cluster (ISC) assembly machinery consists of 17 proteins
      that operate in three major steps of the maturation process. First, the cysteine
      desulfurase complex Nfs1-Isd11 as the sulfur donor cooperates with ferredoxin
      ferredoxin reductase acting as an electron transfer chain, and frataxin to
      synthesize an [2Fe-2S] cluster on the scaffold protein Isu1. Second, the cluster
      is released from Isu1 and transferred toward apoproteins with the help of a
      dedicated Hsp70 chaperone system and the glutaredoxin Grx5. Finally, various
      specialized ISC components assist in the generation of [4Fe-4S] clusters and
      cluster insertion into specific target apoproteins. Functional defects of the
      core ISC assembly machinery are signaled to cytosolic or nuclear iron regulatory
      systems resulting in increased cellular iron acquisition and mitochondrial iron
      accumulation. In fungi, regulation is achieved by iron-responsive transcription
      factors controlling the expression of genes involved in iron uptake and
      intracellular distribution. They are assisted by cytosolic multidomain
      glutaredoxins which use a bound Fe/S cluster as iron sensor and additionally
      perform an essential role in intracellular iron delivery to target
      metalloproteins. In mammalian cells, the iron regulatory proteins IRP1, an Fe/S
      protein, and IRP2 act in a post-transcriptional fashion to adjust the cellular
      needs for iron. Thus, Fe/S protein biogenesis and cellular iron metabolism are
      tightly linked to coordinate iron supply and utilization. This article is part of
      a Special Issue entitled: Cell Biology of Metals.

PMID- 22609303
TI  - The chloroethylating anticancer drug ACNU induces FRA1 that is involved in drug
      resistance of glioma cells.
AB  - FRA1 belongs, together with c-Fos and FosB, to the family of Fos proteins that
      form with members of the ATF and Jun family the transcription factor AP-1
      (activator protein 1). Previously we showed that c-Fos protects mouse embryonic
      fibroblasts against the cytotoxic effects of ultraviolet (UV) light by induction
      of the endonuclease XPF, leading to enhanced nucleotide excision repair (NER)
      activity. Here, we analyzed the regulation of FRA1 in glioma cells treated with
      the anticancer drug nimustine (ACNU) and its role in ACNU-induced toxicity. We
      show that FRA1 is upregulated in glioblastoma cells following ACNU on mRNA and
      protein levels. Knockdown of FRA1 by either siRNA or shRNA clearly sensitized
      glioma cells towards ACNU-induced cell death. Despite decreased AP-1 binding
      activity upon FRA1 knockdown, this effect is independent on regulation of the AP
      1 target genes fasL, ercc1 and xpf. In addition, FRA1 knockdown does not affect
      DNA repair capacity. However, lack of FRA1 attenuated the ACNU-induced
      phosphorylation of CHK1 and led to a reduced arrest of cells in G2/M and,
      thereby, presumably leads to enhanced cell death in the subsequent cell cycle.

PMID- 22609302
TI  - A role for the vesicle-associated tubulin binding protein ARL6 (BBS3) in
      flagellum extension in Trypanosoma brucei.
AB  - The small GTPase Arl6 is implicated in the ciliopathic human genetic disorder
      Bardet-Biedl syndrome, acting at primary cilia in recruitment of the octomeric
      BBSome complex, which is required for specific trafficking events to and from the
      cilium in eukaryotes. Here we describe functional characterisation of Arl6 in the
      flagellated model eukaryote Trypanosoma brucei, which requires motility for
      viability. Unlike human Arl6 which has a ciliary localisation, TbARL6 is
      associated with electron-dense vesicles throughout the cell body following co
      translational modification by N-myristoylation. Similar to the related protein
      ARL-3A in T. brucei, modulation of expression of ARL6 by RNA interference does
      not prevent motility but causes a significant reduction in flagellum length.
      Tubulin is identified as an ARL6 interacting partner, suggesting that ARL6 may
      act as an anchor between vesicles and cytoplasmic microtubules. We provide
      evidence that the interaction between ARL6 and the BBSome is conserved in
      unicellular eukaryotes. Overexpression of BBS1 leads to translocation of
      endogenous ARL6 to the site of exogenous BBS1 at the flagellar pocket.
      Furthermore, a combination of BBS1 overexpression and ARL6 RNAi has a synergistic
      inhibitory effect on cell growth. Our findings indicate that ARL6 in trypanosomes
      contributes to flagellum biogenesis, most likely through an interaction with the
      BBSome.

PMID- 22609304
TI  - First report on natural infection of the Phlebotomus tobbi by Leishmania infantum
      in northwestern Iran.
AB  - Visceral leishmaniasis (VL) is an important health problem in Ardebil, where it
      borders Azerbaijan in the northwestern Iran. In spite of the presence of both
      cutaneous and visceral leishmaniasis (CL and VL) in northwestern Iran, previous
      researches have consistently revealed the etiologic agent of VL in the region to
      be Leishmania infantum. This is the first report of natural infection of
      Phlebotomus tobbi with L. infantum in Bilesavar district in the northern part of
      Ardebil province bordering Azerbaijan. Polymerase chain reaction (PCR) of kDNA,
      ITS1-rDNA, and CPB genes of the parasite followed by restriction fragment length
      polymorphism (RFLP) and gene sequencing analyses revealed presence of L. infantum
      in six out of 433 tested female sand fly specimens. Although sand flies of P.
      tobbi were infrequent, two out of 32 (6.25%) females captured in the area were
      found infected with the parasite. Phlebotomus perfiliewi transcaucasicus, the
      known vector of VL in the area, were the most dominant species but only four out
      of 273 (1.47%) tested were infected with L. infantum. This study showed that P.
      tobbi similar to P. perfiliewi transcaucasicus could play a significant role in
      the transmission of the L. infantum. However more investigations are needed to
      demonstrate that L. infantum is the only species circulating in the focus.

PMID- 22609305
TI  - Trypanosoma evansi: effects of zinc and copper in experimentally infected rats.
AB  - The aim of this study was to evaluate the effects of a treatment using injectable
      zinc and copper in rats infected with Trypanosoma evansi. 48 rats were divided
      into eight groups of six animals each. Group A was composed of uninfected
      animals. Animals from groups B-H were inoculated at the 5th day of experiment
      with 1.2*10(6) trypanosomes. Group B was used as a positive control. The infected
      groups received prophylactic (C, D and E) and therapeutic (F, G and H) treatments
      with the zinc and copper, both at a dose of 5 mg kg(-1). The effectiveness of
      treatment was confirmed by negative blood smears and Polymerase Chain Reaction
      (PCR) at the end of study. All treated animals had their prepatent period and
      survival prolonged when compared with control group (group B). Treatment efficacy
      was 17% (C: zinc), 33% (D: copper), 50% (E: zinc+copper), 0% (F: zinc), 50% (G:
      copper) and 50% (H: zinc+copper). Thus, we can conclude that treatment with zinc
      and copper are capable of controlling and/or curing T. evansi infection in rats,
      delaying the parasitemia and prolonging their survival.

PMID- 22609306
TI  - Single nucleotide polymorphisms and risk of hepatocellular carcinoma in
      cirrhosis.
AB  - Liver carcinogenesis is a complex and multi-factorial process, in which both
      environmental and genetic features interfere and contribute to malignant
      transformation. Patients with cirrhosis are particularly exposed and justify
      periodical screenings in order to detect the early development of hepatocellular
      carcinoma (HCC). The risk of HCC is, however, not identical from one patient to
      another. The identification of host factors that may also play an important role
      in HCC development may improve our understanding of the implications of the
      various biological pathways involved in liver carcinogenesis; such progress may
      as well help refine the selection of patients who could benefit from specific
      preventative measures or could be given adapted screening policies. Numerous
      candidate-gene studies have reported associations between single nucleotide
      polymorphisms (SNPs) and the presence of HCC. Some of these publications
      unfortunately suffer from major methodological drawbacks because of their case
      control, retrospective and monocentric aspect. Prospective cohort studies
      conducted in large homogeneous populations and comprising a sufficient number of
      events during follow-up may overcome these pitfalls, but require a long time to
      be conducted and are still scarce. More recently, the first Genome Wide
      Association studies (GWAs) have enabled the identification of unsuspected loci
      that may be involved in various steps implicated in liver tumourigenesis. Taken
      together, these studies highlight variants that modulate oxidative stress, iron
      metabolism, inflammatory and immune responses, DNA repair mechanisms or systems
      involved in cell-cycle regulation as genetic traits susceptible to modify the
      natural history of cirrhotic patients and partly explain the observed differences
      in the risk of HCC occurrence. However, large genetic epidemiology studies in the
      field of cancer diseases have suggested the limited ability of polymorphic
      traits, alone, to refine individual prognosis. The integration of various panels
      of genes into clinical scores may in the near future define a "genomic risk
      prediction" specific to liver cancer developed in cirrhotic patients.

PMID- 22609307
TI  - Evolution of indications and results of liver transplantation in Europe. A report
      from the European Liver Transplant Registry (ELTR).

PMID- 22609308
TI  - Gap junctions and non-neoplastic liver disease.
AB  - Because of their critical role as goalkeepers of hepatic homeostasis, gap
      junctions are frequent targets in liver disease. This concept has been
      demonstrated on many occasions in the light of hepatocarcinogenesis. Relatively
      little focus has been put on the fate of gap junctions in other liver
      pathologies, including hepatitis, liver fibrosis and cirrhosis, cholestasis and
      hepatic ischemia and reperfusion injury. The present paper provides an in-depth
      description of the multiple changes in expression, localization and function of
      connexins, the molecular constituents of gap junctions. The use of connexins as
      biomarkers and therapeutic targets in liver disease is also illustrated.

PMID- 22609309
TI  - Successful mutation-specific chaperone therapy with 4-phenylbutyrate in a child
      with progressive familial intrahepatic cholestasis type 2.
AB  - BACKGROUND & AIMS: Progressive familial intrahepatic cholestasis type 2 (PFIC2)
      is due to mutations in ABCB11 encoding the canalicular bile salt export pump
      (BSEP) of hepatocyte. Liver transplantation is usually required. 4-phenylbutyrate
      (4-PB) has been shown in vitro to retarget some selected mutated apical
      transporters. After an in vitro study in a hepatocellular polarized line, we
      tested 4-PB treatment in a child with a homozygous p.T1210P BSEP mutation.
      METHODS: Can 10 cells were transfected with plasmids encoding wild type Bsep
      (Bsep(wt)) and mutated p.T1210P Bsep (Bsep(T1210P)), both tagged with GFP. Then,
      cells were treated with 4-PB at 37 or 27 degrees C, immunostained and analyzed
      using confocal microscopy. The child received 4-PB orally in two divided doses
      and BSEP liver immunostaining was performed before and after 4-PB as well as bile
      analysis. RESULTS: In Can 10 cells, in contrast to Bsep(wt)-GFP, Bsep(T1210P)-GFP
      was not detected at the canalicular membrane but in the endoplasmic reticulum. 4
      PB as well as incubation at 27 degrees C partially corrected Bsep(T1210P)-GFP
      targeting to the canalicular membrane, while combined treatments resulted in
      normal canalicular localization. In the child, we showed that 4-PB improved
      clinical and biological parameters of cholestasis and liver function. Also,
      canalicular expression of p.T1210P BSEP mutant was partially corrected as was
      biliary bile acid excretion. CONCLUSIONS: The results illustrate for the first
      time the therapeutic potential of a clinically approved chaperone drug in a
      selected patient with PFIC2 and support that bile secretion improvement might be
      due to the ability of 4-PB to retarget mutated BSEP.

PMID- 22609310
TI  - Increased density of macrophage migration inhibitory factor (MIF) in tuberculosis
      granuloma.
AB  - Granulomas, the pathologic hallmarks of tuberculosis, are composed of tightly
      numerous immune cells that respond to a variety of persistent stimuli during
      pathogen-host interaction. The granuloma is essential for host containment of
      mycobacterial infection, however, the mechanism of host and pathogen determinants
      to recruit immune cells at the site of inflammation and the formation of
      granulomas remains elusive until now. Macrophage migration inhibitory factor
      (MIF), a cytokine produced by many cell types, modulates cellular and humoral
      immune responses and promote lymphocytes migration to the site of infection. In
      this study, we evaluate the expression of MIF in tuberculous granulomas by three
      different models of diseases: mouse, human tissues and zebrafish. The overall
      results demonstrated that the expression of MIF positive signals markedly
      increased in the tissues which have been infected with mycobacterium, whereas a
      few presence of MIF in the PBS-treated animals (means the control group). In the
      mycobacterial-infected animals, the MIF positives distributed extensively within
      the granuloma especially in the multinucleated giant cells. Thus, three
      independent lines of evidence support the hypothesis that MIF may be an important
      player in aggregate immune cells to the granuloma microenvironments in these
      animal models of tuberculosis.

PMID- 22609311
TI  - Endothelial cell activation promotes foam cell formation by monocytes following
      transendothelial migration in an in vitro model.
AB  - Foam cells are a pathological feature present at all stages of atherosclerosis.
      Foam cells develop from monocytes that enter the nascent atheroma and
      subsequently ingest modified low density lipoproteins (LDL). The regulation of
      this process has previously been studied in vitro using cultured macrophage fed
      modified LDL. We used our existing in vitro model of transendothelial migration
      (TEM) to study this process in a more physiologically relevant setting. In our
      model, monocytes undergo TEM across a primary endothelial monolayer into an
      underlying three-dimensional collagen matrix in the presence of 20% human serum.
      Foam cells were detected by Oil Red O staining for intracellular lipid droplets.
      We demonstrate that sub-endothelial monocytes can develop into foam cells within
      48 h of TEM across TNF-alpha activated endothelium, in the absence of additional
      lipids. Our data indicate a role for both monocyte-endothelial interactions and
      soluble factors in the regulation of foam cell development, including oxidation
      of LDL in situ from lipid present in culture medium following TNF-alpha
      stimulation of the endothelial cells. Our study provides a simple model for
      investigating foam cell development in vitro that mimics cell migration in vivo,
      and demonstrates the critical role of inflammation in regulating early
      atherogenic events.

PMID- 22609313
TI  - Follow-up after surgical treatment of bladder cancer: a critical analysis of the
      literature.
AB  - CONTEXT: Follow-up of patients treated for bladder cancer (BCa) is of great
      importance for both non-muscle-invasive BCa (NMIBC) and muscle-invasive BCa
      (MIBC) because of the high incidence of recurrence and progression. The schedule
      and methods of follow-up should reflect the individual clinical situation.
      OBJECTIVE: To evaluate the existing evidence for intensity and duration of follow
      up recommendations in patients after surgical treatment of BCa. EVIDENCE
      ACQUISITION: We searched the Medline, Embase, and Cochrane databases for
      published data on the follow-up of patients with NMIBC and MIBC after radical
      cystectomy (RC). EVIDENCE SYNTHESIS: Follow-up in patients with NMIBC is
      necessary because of the high probability of tumour recurrence and the risk of
      progression. Cystoscopy plus cytology are the standard methods for follow-up.
      Cystoscopy should be done 3 mo after the transurethral resection in every
      patient, and the frequency after that depends on the individual
      recurrence/progression risk. Cytology should be used as an adjunctive method to
      cystoscopy in intermediate- and high-risk patients. None of the currently
      available urinary markers or imaging methods can substitute for cystoscopy-based
      follow-up. High-risk NMIBC patients require regular lifelong upper urinary tract
      monitoring. Follow-up in MIBC is based on the fact that early detection of
      recurrence after RC allows for timely treatment with the aim of improving
      outcomes. Patients with extravesical and lymph node-positive disease should have
      the most intensive follow-up because of the highest recurrence risk. Routine
      upper urinary tract imaging is advisable for all patients and should continue in
      the long term. Follow-up also allows for early detection of urinary diversion
      related complications, the rate of which increases with time. CONCLUSIONS: Follow
      up in BCa is necessary for diagnosing recurrence and progression, as well as for
      evaluating complications after radical treatment. Since randomised studies
      investigating the most appropriate follow-up schedule are lacking, most
      recommendations are based on only the retrospective experience. Nonetheless,
      reasonable recommendations can be made until further prospective randomised
      studies testing different follow-up schedules have been performed.

PMID- 22609312
TI  - Bmi1 is required for regeneration of the exocrine pancreas in mice.
AB  - BACKGROUND & AIMS: Bmi1 is a member of the Polycomb protein family and represses
      transcription by modifying chromatin organization at specific promoters. Bmi1 is
      implicated in the control of stem cell self-renewal and has been shown to
      regulate cell proliferation, tissue homeostasis, and differentiation. Bmi1 is
      present in a subpopulation of self-renewing pancreatic acinar cells and is
      expressed in response to pancreatic damage. We investigated the role of Bmi1 in
      regeneration of exocrine pancreas. METHODS: Acute pancreatitis was induced in
      Bmi1(-/-) mice with cerulein; pancreatic cell regeneration, differentiation, and
      apoptosis were assessed. Cultured Bmi1(-/-) and wild-type primary acini were
      analyzed in vitro to determine acinar-specific consequences of Bmi1 deletion. To
      investigate cell autonomous versus non-cell autonomous roles for Bmi1 in vivo,
      pancreatitis was induced in Bmi1(-/-) mice reconstituted with a wild-type
      hematopoietic system. RESULTS: Bmi1 expression was up-regulated in the exocrine
      pancreas during regeneration after cerulein-induced pancreatitis. Exocrine
      regeneration was impaired following administration of cerulein to Bmi1(-/-) mice.
      Pancreata of Bmi1(-/-) mice were hypoplastic, and the exocrine pancreas was
      replaced with ductal metaplasia that had increased apoptosis and decreased cell
      proliferation compared with that of wild-type mice. Expression of Cdkn2a and p53
      dependent apoptotic genes was markedly up-regulated in Bmi1(-/-) pancreas
      compared with wild-type mice after injury. Furthermore, after transplantation of
      bone marrow from wild-type to Bmi1(-/-) mice, the chimeric mice had intermediate
      levels of pancreatic hypoplasia and significant but incomplete rescue of impaired
      exocrine regeneration after cerulein injury. CONCLUSIONS: Bmi1 contributes to
      regeneration of the exocrine pancreas after cerulein-induced injury through cell
      autonomous mechanisms, in part by regulating Cdkn2a expression, and non-cell
      autonomous mechanisms.

PMID- 22609314
TI  - Sexual hormones: effects on cardiac and mitochondrial activity after ischemia
      reperfusion in adult rats. Gender difference.
AB  - In this work we studied the influence of sex hormones on heart and mitochondrial
      functions, from adult castrated female and male, and intact rats. Castration was
      performed at their third week of life and on the fourth month animals were
      subjected to heart ischemia and reperfusion. Electrocardiogram and blood pressure
      recordings were made, cytokines levels were measured, histopathological studies
      were performed and thiobarbituric acid reactive species were determined. At the
      mitochondrial level respiratory control, transmembranal potential and calcium
      management were determined; Western blot of some mitochondrial components was
      also performed. Alterations in cardiac function were worst in intact males and
      castrated females as compared with those found in intact females and castrated
      males, cytokine levels were modulated also by hormonal status. Regarding
      mitochondria, in those obtained from hearts from castrated females without
      ischemia-reperfusion, all evaluated parameters were similar to those observed in
      mitochondria after ischemia-reperfusion. The results show hormonal influences on
      the heart at functional and mitochondrial levels.

PMID- 22609316
TI  - Comparison of the long-term consequences of withdrawal from repeated amphetamine
      exposure in adolescence and adulthood on information processing and locomotor
      sensitization in mice.
AB  - Repeated administration of the indirect dopamine receptor agonist amphetamine
      (AMPH) produces robust locomotor sensitization and additional behavioral
      abnormalities. Accumulating evidence suggests that the developmental timing of
      drug exposure can critically influence this effect. The present study compared
      the consequences of withdrawal from repeated AMPH exposure in adolescence and
      adulthood on information processing and locomotor sensitization in C57BL/6 mice.
      Animals were injected daily with AMPH (1 or 2.5 mg/kg) or vehicle on 7
      consecutive days starting either from postnatal day 35 to 42, or from postnatal
      day 70 to 77, following which they were given a 4 week withdrawal period before
      behavioral and pharmacological testing commenced. We found that withdrawal from
      the higher dose of AMPH (2.5 mg/kg/day) given either in adolescence or adulthood
      similarly disrupted selective associative learning as measured by the latent
      inhibition paradigm. None of the AMPH withdrawal groups displayed alterations in
      sensorimotor gating in the form of prepulse inhibition. Withdrawal from adult
      AMPH exposure at both doses induced marked locomotor sensitization, whereas
      adolescent pre-treatment with the higher (2.5 mg/kg/day) but not lower (1
      mg/kg/day) dose of AMPH potentiated the locomotor-enhancing effects of acute AMPH
      re-challenge. Our study suggests that withdrawal from repeated AMPH exposure in
      adolescence and adulthood has similar consequences on selective associative
      learning, but the two manipulations differ with respect to their efficacy to
      induce long-term locomotor sensitization to the drug. The latter finding supports
      the hypothesis that the precise developmental timing determines, at least in
      part, the impact on long-term dopamine-associated sensitization processes.

PMID- 22609317
TI  - Antidepressants act directly on astrocytes: evidences and functional
      consequences.
AB  - Post-mortem histopathological studies report on reduced glial cell numbers in
      various frontolimbic areas of depressed patients implying that glial loss
      together with abnormal functioning could contribute to the pathophysiology of
      mood disorders. Astrocytes are regarded as the most abundant cell type in the
      brain and known for their housekeeping functions, but as recent developments
      suggest, they are also dynamic regulators of synaptogenesis, synaptic strength
      and stability and they control adult hippocampal neurogenesis. The primary aim of
      this review was to summarize the abundant experimental evidences demonstrating
      that antidepressant therapies have profound effect on astrocytes. Antidepressants
      modify astroglial physiology, morphology and by affecting gliogenesis they
      probably even regulate glial cell numbers. Antidepressants affect intracellular
      signaling pathways and gene expression of astrocytes, as well as the expression
      of receptors and the release of various trophic factors. We also assess the
      potential functional consequences of these changes on glutamate and glucose
      homeostasis and on synaptic communication between the neurons. We propose here a
      hypothesis that antidepressant treatment not only affects neurons, but also
      activates astrocytes, triggering them to carry out specific functions that result
      in the reactivation of cortical plasticity and can lead to the readjustment of
      abnormal neuronal networks. We argue here that these astrocyte specific changes
      are likely to contribute to the therapeutic effectiveness of the currently
      available antidepressant treatments and the better understanding of these
      cellular and molecular processes could help us to identify novel targets for the
      development of antidepressant drugs.

PMID- 22609315
TI  - Cognitive contributions of the ventral parietal cortex: an integrative
      theoretical account.
AB  - Although ventral parietal cortex (VPC) activations can be found in a variety of
      cognitive domains, these activations have been typically attributed to cognitive
      operations specific to each domain. In this article, we propose a hypothesis that
      can account for VPC activations across all the cognitive domains reviewed. We
      first review VPC activations in the domains of perceptual and motor reorienting,
      episodic memory retrieval, language and number processing, theory of mind, and
      episodic memory encoding. Then, we consider the localization of VPC activations
      across domains and conclude that they are largely overlapping with some
      differences around the edges. Finally, we assess how well four different
      hypotheses of VPC function can explain findings in various domains and conclude
      that a bottom-up attention hypothesis provides the most complete and parsimonious
      account.

PMID- 22609318
TI  - Seasonal variation and trends in stroke hospitalizations and mortality in a South
      American community hospital.
AB  - Numerous studies have reported the presence of temporal variations in biological
      processes. Seasonal variation (SV) in stroke has been widely studied, but little
      data have been published on this phenomenon in the Southern Hemisphere, and there
      have been no studies reported from Argentina. The goals of the present study were
      to describe the SV of admissions and deaths for stroke and examine trends in
      stroke morbidity and mortality over a 3-year period in a community hospital in
      Argentina. Hospital discharge reports from the electronic database of vital
      statistics between 1999 and 2001 were examined retrospectively. Patients who had
      a main discharge diagnosis of stroke (ischemic or hemorrhagic) or cerebrovascular
      accident (International Classification of Diseases, Ninth Revision codes 431,
      432, 434, and 436) were selected. The study sample included 1382 hospitalizations
      by stroke (3.5% of all admissions). In-hospital mortality demonstrated a winter
      peak (25.5% vs 17% in summer; P = .001). The crude seasonal stroke attack rate
      (ischemic and hemorrhagic) was highest in winter (164 per 100,000 population; 95%
      CI, 159-169 per 100,000) and lowest in summer (124 per 100,000; 95% CI, 120-127
      per 100,000; P = .008). Stroke admissions followed a seasonal pattern, with a
      winter-spring predominance (P = .008). Our data indicate a clear SV in stroke
      deaths and admissions in this region of Argentina. The existence of SV in stroke
      raises a different hypothesis about the rationale of HF admissions and provides
      information for the organization of care and resource allocation. 

PMID- 22609319
TI  - Improving the prediction of stroke or death after transient ischemic attack (TIA)
      by adding diffusion-weighted imaging lesions and TIA etiology to the ABCD2 score.
AB  - The present study investigated the addition of transient ischemic attack (TIA)
      etiology and diffusion-weighted imaging (DWI) to the ABCD2 score, creating the
      ABCDE+ score, to improve the predictive ability of stroke risk or death at 6
      months after TIA. We performed a cohort study of 150 consecutive patients with
      TIA. All patients underwent DWI and all had an etiologic workup and were followed
      up for 6 months. The area under the receiver operating characteristic curve (AUC)
      was used to compare the scores' ability to predict the outcome of stroke or
      death. Multivariate Cox regression analysis was performed to evaluate the
      association between the measured variables and subsequent stroke or death. Thirty
      patients (20%) experienced future stroke, and 12 patients (8%) died within the 6
      month follow-up. A comparison of AUCs demonstrated the superiority of the ABCDE+
      score over the ABCD2 score for predicting stroke (0.64 vs 0.60) and for
      predicting death (0.62 vs 0.56). ABCD2 score >4, ABCDE+ score >6, large-artery
      disease, and lesions detected on DWI were found to be independent predictors of
      future stroke, and ABCDE+ score >6, age, and heart disease were independent
      predictors of death. We conclude that incorporating DWI positivity and etiology
      of TIA into the ABCD2 score can improve the ability to predict stroke and death
      within 6 months after TIA. 

PMID- 22609320
TI  - Elastographic assessment of liver fibrosis in children: A prospective single
      center experience.
AB  - BACKGROUND: The assessment of liver damage in various disease states relies on a
      combination of clinical findings, biochemical parameters and invasive tests such
      as liver biopsy. The ultrasound elastography has emerged as a potential
      alternative test, providing quantifiable information on the elasticity/stiffness
      of the examined-tissues. We assessed the performance of ultrasound elastography
      using real-time Acoustic Radiation Force Imaging (ARFI) technology in evaluating
      the degree of liver fibrosis in children with and without liver disease. METHODS:
      Children aged 0-18 years, hospitalized in the Emergency Clinical County Hospital
      Tg. Mures, Romania, between September 15, 2010 and January 15, 2011, were
      eligible for the study. Four groups were recruited as follow: patients with liver
      disease in the setting of various malignant disorders, children with non
      malignant liver disease, overweight and obese children and healthy controls. The
      liver tissue elasticity was assessed in each individual using Shear Wave Velocity
      (SWV). Biochemical tests included transaminase levels. 19 children with chronic
      liver disease underwent biopsies. SWV was measured globally and separately for
      the liver-segments 1 and 8. Correlations between the SWV and laboratory test were
      established using non-parametric Spearman correlation test. RESULTS: A total of
      103 children underwent liver ultrasound elastographic assessments. Of these, 39
      had malignancies, 19 had various chronic liver diseases, 13 had nonalcoholic
      fatty liver disease (NAFLD), and 32 were healthy controls. The transaminase
      values differed significantly between children with liver diseases and controls.
      In normal controls SWV values in the 1st segment were significantly lower
      compared to those in the in 8th segment of the liver (p=0.0216). In the group
      with hepatic steatosis, the SWV values were statistically higher compared to
      those in healthy controls. Positive statistical correlations have been
      established between AST and SWV in the group of children with NAFLD and those
      with malignancies (p=0.0032, p=0.0045). CONCLUSIONS: Quantification of liver
      fibrosis by ARFI method correlates with the histological fibrosis stage in
      children with chronic liver disease and NAFLD. Clinical applications of this
      method in the diagnosis of pediatric liver disease deserve further study.

PMID- 22609321
TI  - MR determination of neonatal spinal canal depth.
AB  - OBJECTIVES: Lumbar punctures (LPs) are frequently performed in neonates and often
      result in traumatic haemorrhagic taps. Knowledge of the distance from the skin to
      the middle of the spinal canal (mid-spinal canal depth - MSCD) may reduce the
      incidence of traumatic taps, but there is little data in extremely premature or
      low birth weight neonates. Here, we determined the spinal canal depth at post
      mortem in perinatal deaths using magnetic resonance imaging (MRI). PATIENTS AND
      METHODS: Spinal canal depth was measured in 78 post-mortem foetuses and perinatal
      cases (mean gestation 26 weeks; mean weight 1.04kg) at the L3/L4 inter-vertebral
      space at post-mortem MRI. Both anterior (ASCD) and posterior (PSCD) spinal canal
      depth were measured; MSCD was calculated and modelled against weight and
      gestational age. RESULTS: ASCD and PSCD (mm) correlated significantly with weight
      and gestational age (all r>0.8). A simple linear model MSCD (mm)=3*Weight (kg)+5
      was the best fit, identifying an SCD value within the correct range for 87.2%
      (68/78) (95% CI (78.0, 92.9%)) cases. Gestational age did not add significantly
      to the predictive value of the model. CONCLUSION: There is a significant
      correlation between MSCD and body weight at post-mortem MRI in foetuses and
      perinatal deaths. If this association holds in preterm neonates, use of the
      formula MSCD (mm)=3*Weight (kg)+5 could result in fewer traumatic LPs in this
      population.

PMID- 22609322
TI  - Unique mitochondrial DNA in highly inbred feral cattle.
AB  - The Chillingham herd of wild Northumbrian cattle remains viable despite over 300
      years of in-breeding and a near-homozygous nuclear genome. Here we report the
      complete mitochondrial DNA sequence using ultra-deep next generation sequencing.
      Random population sampling of ~10% of the extant herd identified a single mtDNA
      haplotype harbouring a unique bovine variant present in all other higher mammals
      (m.11789C/Y421H) which may contribute to their survival.

PMID- 22609323
TI  - Mitochondrial dynamics and neuronal fate in Parkinson's disease.
AB  - Along with the impairment of mitochondrial respiration both mitochondrial
      fission/fusion and mitophagy have been shown to be altered in Parkinson's disease
      (PD). In both genetic and toxin-induced models of PD an imbalance in
      mitochondrial morphology is evident, as its correction through modulation of the
      fission/fusion proteins has been shown to be protective. From the study of the PD
      associated genes, namely PINK1 and Parkin, compromised mitochondrial clearance
      through mitophagy has been associated with the disease etiopathogenesis. Here we
      propose that an interplay between defective mitochondrial morphology and
      clearance arises as a crucial player in sentencing neuronal fate in PD.

PMID- 22609324
TI  - New perspectives on assembling c-type cytochromes, particularly from sulphate
      reducing bacteria and mitochondria.
AB  - Some recent new developments emerging from studies of the Systems I and III for c
      type cytochrome biogenesis are discussed, particularly in regard to developments
      in studying System I in sulphate reducing bacteria. This article is part of a
      Special Issue entitled: 17th European Bioenergetics Conference (EBEC 2012).

PMID- 22609325
TI  - The Alternative complex III: properties and possible mechanisms for electron
      transfer and energy conservation.
AB  - Alternative complexes III (ACIII) are recently identified membrane-bound enzymes
      that replace functionally the cytochrome bc(1/)b(6)f complexes. In general, ACIII
      are composed of four transmembrane proteins and three peripheral subunits that
      contain iron-sulfur centers and C-type hemes. ACIII are built by a combination of
      modules present in different enzyme families, namely the complex iron-sulfur
      molybdenum containing enzymes. In this article a historical perspective on the
      investigation of ACIII is presented, followed by an overview of the present
      knowledge on these enzymes. Electron transfer pathways within the protein are
      discussed taking into account possible different locations (cytoplasmatic or
      periplasmatic) of the iron-sulfur containing protein and their contribution to
      energy conservation. In this way several hypotheses for energy conservation modes
      are raised including linear and bifurcating electron transfer pathways. This
      article is part of a Special Issue entitled: 17th European Bioenergetics
      Conference (EBEC 2012).

PMID- 22609326
TI  - Pregnancy outcome after paternal exposure to azathioprine/6-mercaptopurine.
AB  - There are only few studies with conflicting results on pregnancy outcome after
      paternal exposure to azathioprine or 6-mercaptopurine. In our study, pregnancy
      outcome of 115 prospectively followed pregnancies after paternal exposure to
      azathioprine or 6-mercaptopurine is compared to a control group of 341
      pregnancies. The rate of major malformations was not increased (3.0% in exposed
      versus 2.2% in the control group). There was no specific pattern of birth defects
      and no indication for chromosomal aberrations in the exposed group. We observed a
      higher rate of elective terminations of pregnancy in the exposed group and a non
      significant increase of spontaneous abortions (cumulative incidence 19% versus
      13%, respectively). Further prospective studies are required to address the
      question of a possibly increased risk for spontaneous abortion.

PMID- 22609327
TI  - A thin-film bulk acoustic resonator and filter with optimal edge shapes for mass
      production.
AB  - The manufacturing conditions of a thin-film bulk acoustic resonator (FBAR) filter
      were investigated to obtain a high Q factor which is stable for mass production.
      The FBAR consist of patterned electrodes and piezoelectric films. In this study,
      the influence of edge shape of the films on the anti-resonance characteristics
      was investigated using a numerical method. Optimized shape was applied to a 2.5
      GHz band resonator and filter. As a result, significant improvement of the Q
      factor and the insertion loss was confirmed.

PMID- 22609328
TI  - Novel 16S rRNA based PCR method targeting Deinococcus spp. and its application to
      assess the diversity of deinococcal populations in environmental samples.
AB  - The members of the genus Deinococcus are extensively studied because of their
      exemplary radiation resistance. Both ionizing and non-ionizing rays are routinely
      employed to select upon the radiation resistant deinococcal population and
      isolate them from the majority of radiation sensitive population. There are no
      studies on the development of molecular tools for the rapid detection and
      identification of deinococci from a mixed population without causing the bias of
      radiation enrichment. Here we present a Deinococcus specific two-step hemi-nested
      PCR for the rapid detection of deinococci from environmental samples. The method
      is sensitive and specific to detect deinococci without radiation exposure of the
      sample. The new protocol was successfully employed to detect deinococci from
      several soil samples from different geographical regions of India. The PCR method
      could be adapted to a three-step protocol to study the diversity of the
      environmental deinococcal population by denaturing gradient gel electrophoresis
      (DGGE). Sequence analysis of the DGGE bands revealed that the samples harbor
      diverse populations of deinococci, many of which were not recovered by culturing
      and may represent novel clades. We demonstrate that the genus specific primers
      are also suitable for the rapid identification of the bacterial isolates that are
      obtained from a typical radiation enrichment isolation technique. Therefore the
      primers and the protocols described in this study can be used to study
      deinococcal diversity from environmental samples and can be employed for the
      rapid detection of deinococci in samples or identifying pure culture isolates as
      Deinococcus species.

PMID- 22609329
TI  - Paramyxean-microsporidian co-infection in amphipods: is the consensus that
      Microsporidia can feminise their hosts presumptive?
AB  - The current consensus is that Microsporidia belong to a select group of parasites
      capable of causing both intersexuality and complete sex reversal in their hosts.
      Indeed, species such as Nosema granulosis and Dictyocoela duebenum, which infect
      amphipod crustaceans, are regularly referred to as 'feminising microsporidians'.
      This categorisation is based on a combination of findings: that these species are
      vertically transmitted and occur at a high prevalence of infection in intersex
      and female amphipods, that infected amphipod populations are female-biased, and
      that infected females have significantly female-biased broods with no concurrent
      increase in mortality. In this study, we report on a population of the amphipod
      Echinogammarus marinus presenting both female bias and high levels of
      intersexuality, which are infected with D. deubenum. In keeping with its
      feminising classification, infection is prevalent in animals presenting female
      and intersex phenotypes. However, a further screen revealed the presence of a
      previously unknown paramyxean parasite related to organisms of the genus
      Marteilia, a group known to cause catastrophic sexual dysfunction in bivalves. We
      found that the paramyxean parasite was also vertically transmitted, with
      infections being more prevalent in females and intersex animals. Critically,
      every animal infected with D. deubenum was also co-infected with the paramyxean,
      with few animals presenting an independent paramyxean infection. In contrast, co
      infection of E. marinus with a paramyxean and the non-feminising microsporidian
      Dictyocoela berillonum rarely occurred. These observations raise a new
      hypothesis, namely, that D. duebenum and other feminising microsporidians are not
      actually capable of host feminisation but instead 'hitch-hike' together with a
      feminising paramyxean parasite.

PMID- 22609330
TI  - Concurrent silent strokes impair motor function by limiting behavioral
      compensation.
AB  - Silent strokes occur more frequently than classic strokes; however, symptoms may
      go unreported in spite of lasting tissue damage. A silent stroke may indicate
      elevated susceptibility to recurrent stroke, which may eventually result in
      apparent and lasting impairments. Here we investigated if multiple silent strokes
      to the motor system challenge the compensatory capacity of the brain to
      cumulatively result in permanent functional deficits. Adult male rats with focal
      ischemia received single focal ischemic mini-lesions in the sensorimotor cortex
      (SMC) or the dorsolateral striatum (DLS), or multiple lesions affecting both SMC
      and DLS. The time course and outcome of motor compensation and recovery were
      determined by quantitative and qualitative assessment of skilled reaching and
      skilled walking. Rats with SMC or DLS lesion alone did not show behavioral
      deficits in either task. However, the combination of focal ischemic lesions in
      SMC and DLS perturbed skilled reaching accuracy and disrupted forelimb placement
      in the ladder rung walking task. These observations suggest that multiple focal
      infarcts, each resembling a silent stroke, gradually compromise the plastic
      capacity of the motor system to cause permanent motor deficits. Moreover, these
      findings support the notion that cortical and subcortical motor systems cooperate
      when adopting beneficial compensatory movement strategies.

PMID- 22609331
TI  - Norepinephrine differentially modulates the innate inflammatory response provoked
      by amyloid-beta peptide via action at beta-adrenoceptors and activation of
      cAMP/PKA pathway in human THP-1 macrophages.
AB  - Evidence indicates that norepinephrine (NE) has antiinflammatory activities and
      plays a neuroprotective role where inflammatory events contribute to Alzheimer's
      disease pathology. Here, we evaluated the effects of NE on amyloid beta 1-42
      (Abeta1-42)-induced cytotoxicity and proinflammatory cytokine/chemokine
      secretion, and determined the mechanisms through which NE exerts its actions in
      human THP-1 macrophages. NE clearly reduced the Abeta1-42-mediated production of
      the proinflammatory chemokine, monocytic chemotactic protein-1 (MCP-1/CCL2). In
      contrast to its ability to reduce MCP-1 secretion, NE enhanced the amounts of the
      proinflammatory cytokine interleukin (IL)-1beta secreted from Abeta1-42 treated
      cells. NE significantly reduced the Abeta1-42-induced cytotoxicity in situations
      where it contributed to the increased IL-1beta and decreased MCP-1 during Abeta1
      42 stimulation. The ability of NE to differentially modulate the Abeta1-42
      induced immune responses was mediated by beta-adrenoceptors, as the
      aforementioned effects were replicated by the beta-adrenoceptor agonist,
      isoproterenol, and blocked by the beta-adrenoceptor antagonist, dl-propranolol.
      Of note, the NE effects on Abeta1-42-induced responses were mimicked by dbcAMP
      and forskolin, but significantly blocked by H89, an inhibitor of PKA. Moreover,
      NE abolished Abeta1-42-mediated decline of CREB phosphorylation. Overall, NE
      suppresses Abeta1-42-mediated cytotoxicity and MCP-1 secretion, but enhances
      Abeta-mediated IL-1beta secretion through action at beta-adrenoceptors,
      accompanied by activation of cAMP/PKA pathway and CREB in human microglia-like
      THP-1 cells.

PMID- 22609332
TI  - DOR activation inhibits anoxic/ischemic Na+ influx through Na+ channels via PKC
      mechanisms in the cortex.
AB  - Activation of delta-opioid receptors (DOR) is neuroprotective against
      hypoxic/ischemic injury in the cortex, which is at least partially related to its
      action against hypoxic/ischemic disruption of ionic homeostasis that triggers
      neuronal injury. Na(+) influx through TTX-sensitive voltage-gated Na(+) channels
      may be a main mechanism for hypoxia-induced disruption of K(+) homeostasis, with
      DOR activation attenuating the disruption of ionic homeostasis by targeting
      voltage-gated Na(+) channels. In the present study we examined the role of DOR in
      the regulation of Na(+) influx in anoxia and simulated ischemia (oxygen-glucose
      deprivation) as well as the effect of DOR activation on the Na(+) influx induced
      by a Na(+) channel opener without anoxic/ischemic stress and explored a potential
      PKC mechanism underlying the DOR action. We directly measured extracellular Na(+)
      activity in mouse cortical slices with Na(+) selective electrodes and found that
      (1) anoxia-induced Na(+) influx occurred mainly through TTX-sensitive Na(+)
      channels; (2) DOR activation inhibited the anoxia/ischemia-induced Na(+) influx;
      (3) veratridine, a Na(+) channel opener, enhanced the anoxia-induced Na(+)
      influx; this could be attenuated by DOR activation; (4) DOR activation did not
      reduce the anoxia-induced Na(+) influx in the presence of chelerythrine, a broad
      spectrum PKC blocker; and (5) DOR effects were blocked by PKCbetaII peptide
      inhibitor, and PKCtheta pseudosubstrate inhibitor, respectively. We conclude that
      DOR activation inhibits anoxia-induced Na(+) influx through Na(+) channels via
      PKC (especially PKCbetaII and PKCtheta isoforms) dependent mechanisms in the
      cortex.

PMID- 22609333
TI  - Self-reported rate of eating is significantly associated with body mass index in
      Japanese patients with type 2 diabetes. Japan Diabetes Clinical Data Management
      Study Group (JDDM26).
AB  - We examined whether the rate of eating was associated with the body mass index
      and glycemic control status in Japanese patients with type 2 diabetes (50% women,
      mean+/-SD age 59.4+/-7.5 years). Rapid eating was significantly associated with
      body mass index (p=0.047). The body mass index of those who reported eating
      quickly was 0.8 kg/m2 higher than in individuals who reported eating at medium
      speed even after adjustment for known confounders. No significant association was
      observed between the rate of eating and HbA(1c). Our findings suggest an
      association between self-reported rapid eating and an elevated body mass index in
      patients with type 2 diabetes.

PMID- 22609334
TI  - The food and weight combat. A problematic fight for the elite combat sports
      athlete.
AB  - Weight reduction in athletes is motivated by optimisation of performance,
      aesthetic reasons or to achieve a pre-designated weight. Previous research has
      shown that dietary restraint and short term weight regulation frequently takes
      place among combat sports athletes such as wrestlers and judokas. The aim of this
      study was to explore negative experiences related to dietary strategies and
      weight-making practises used by elite combat sports athletes. Using semi
      structured interviews, 14 Swedish national team athletes in wrestling, judo and
      taekwondo were asked about their dietary intake and their engagement in both long
      and short-term weight regulation practises. Content analysis of the transcribed
      interviews, display a constant struggle regarding nutritional standpoints. Sport
      demands such as achieving an optimal weight and nutritional intake were
      considered as central in order for excellent performance. Adhering to these
      demands was found to be problematic however, primarily because of; (1) negative
      physiological responses and (2) opposing ideals of a non-sport related nature,
      such as the importance of the athletes to be healthy and social in their everyday
      lives.

PMID- 22609335
TI  - Microfluidic technologies for studying synthetic circuits.
AB  - Advances in synthetic biology have augmented the available toolkit of
      biomolecular modules, allowing engineering and manipulation of signaling in a
      variety of organisms, ranging in complexity from single bacteria and eukaryotic
      cells to multi-cellular systems. The richness of synthetic circuit outputs can be
      dramatically enhanced by sophisticated environmental control systems designed to
      precisely pattern spatial-temporally heterogeneous environmental stimuli
      controlling these circuits. Moreover, the performance of the synthetic modules
      and 'blocks' needed to assemble more complicated networks requires more complete
      characterization as a function of arbitrarily complex environmental inputs.
      Microfluidic technologies are poised to meet these needs through a variety of
      innovative designs capitalizing on the unique benefits of manipulating fluids on
      the micro-scales and nano-scales. This review discusses the utility of
      microfluidics for the study of synthetic circuits and highlights recent work in
      the area.

PMID- 22609336
TI  - Isolation of enriched glial populations from post-mortem human CNS material by
      immuno-laser capture microdissection.
AB  - Isolating individual populations of cells from post-mortem (PM) central nervous
      system (CNS) tissue for transcriptomic analysis will provide important insights
      into the pathogenesis of neurodegenerative diseases. To date, research on
      individual CNS cell populations has been hindered by the availability of suitable
      PM material, unreliable sample preparation and difficulties obtaining individual
      cell populations. In this paper we report how rapid immunohistochemistry combined
      with laser capture microdissection (immuno-LCM) enables the isolation of specific
      cell populations from PM CNS tissue, thereby enabling the RNA profile of these
      individual cell types to be investigated. Specifically, we detail methods for
      isolating enriched glial populations (astrocytes, oligodendrocytes and microglia)
      and confirm this cell enrichment by polymerase chain reaction (PCR). In addition,
      the study details the numbers of each glial population required to obtain 50ng
      RNA, a suitable amount of starting material required to carry out microarray
      analysis that potentially may identify alterations of cell-specific genes and
      pathways associated with a range of neurodegenerative disorders.

PMID- 22609337
TI  - Purification of a Tat leader peptide by co-expression with its chaperone.
AB  - We present a method for the purification of the 45 residue long leader peptide of
      Escherichia coli dimethyl sulfoxide reductase subunit A (DmsA(L)), a substrate of
      the twin arginine translocase, by co-expressing the leader peptide with its
      specific chaperone protein, DmsD. The peptide can be isolated from the soluble
      DmsA(L)/DmsD complex or conveniently from the lysate pellet fraction. The
      recombinant leader peptide is functionally intact as the peptide/chaperone
      complex can be reconstituted from purified DmsA(L) and DmsD. A construct with
      DmsA(L) fused to the N-terminus of DmsD (DmsA(L)-DmsD fusion) was created to
      further explore the properties of the leader peptide-chaperone interactions.
      Analytical size-exclusion chromatography in-line with multi-angle light
      scattering reveals that the DmsA(L)-DmsD fusion construct forms a dimer wherein
      each protomer binds the neighboring leader peptide. A model of this homodimeric
      interaction is presented.

PMID- 22609338
TI  - Cloning, expression, purification, and characterization of a novel single-chain
      variable fragment antibody against the 2-nitrobenzaldehyde derivative of a
      furaltadone metabolite in Escherichia coli.
AB  - Furaltadone is an illicit veterinary drug that shows toxic, carcinogenic, and
      mutagenic effects, as does its metabolite 3-amino-5-morpholinomethyl-2
      oxazolidone (AMOZ)(1). Recombinant antibodies with desirable affinity and
      specificity that can replace polyclonal or monoclonal antibodies are important
      factors for effective AMOZ immunoassays. In the present study, a novel single
      chain variable fragment (scFv) antibody against the 2-nitrobenzaldehyde
      derivative of AMOZ (NPAMOZ) was prepared and characterized. The scFv gene was
      cloned into the pET-22b(+) expression vector, and 6His-tagged scFv antibodies
      expressed as inclusion bodies in Escherichia coli BL21 (DE3), which were then
      purified by nickel nitrilotriacetic acid column chromatography. Characterization
      of the target protein by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE), western blotting, and a novel indirect competitive
      chemiluminescence enzyme immunoassay (icCLEIA) showed that the scFv antibody was
      ~27kDa and exhibited HRP-anti-His-tag antibody-recognized activity. The final
      purity, yield and mg of this scFv antibody after ultrafiltration concentration
      were 97%, 20% and 29.1mg, respectively. The icCLEIA indicated that the antibody
      competitively combined with NPAMOZ, exhibiting an IC(50) value of 1.46+/-0.01
      ng/ml (n=6). Cross-reactivity studies revealed that the antibody showed desirable
      specificity to NPAMOZ and little reactivity to analogs except the parent
      furaltadone. In summary, these findings suggested that the prepared recombinant
      scFv antibody can be used for future immunoassay screening for AMOZ.

PMID- 22609339
TI  - Heightened aggressive behavior in mice with lifelong versus postweaning knockout
      of the oxytocin receptor.
AB  - Previous work implicating the neuropeptide oxytocin (Oxt) in the neural
      regulation of aggression in males has been limited. However, there are reports of
      heightened aggression in Oxt knockout and Oxt receptor (Oxtr) knockout male mice
      when they are born to null mutant mothers; suggesting that intrauterine exposure
      to Oxt may be important to normal aggression in adulthood. To explore this, we
      examined aggression in two lines of Oxtr mice, a total knockout (Oxtr-/-), in
      which the Oxtr gene is absent from the time of conception, and a predominantly
      forebrain specific knockout (Oxtr FB/FB), in which the Oxtr gene is not excised
      until approximately 21-28days postnatally. Aggression was measured in males from
      both lines, as well as control littermates, using a resident-intruder behavioral
      test. Consistent with previous reports, male Oxtr-/- mice had elevated levels of
      aggression relative to controls. Oxtr FB/FB mice on the other hand displayed
      levels of aggression similar to control animals. In addition, following a
      resident-intruder test, Oxtr+/+ mice that displayed aggression had less c-fos
      immunoreactivity in the ventral portion of the lateral septum than those that did
      not. Further, Oxtr-/- mice had increased c-fos immunoreactivity in the medial
      amygdala relative to controls. These data suggest that Oxt may play an important
      role during development in the organization of the neural circuits that underlie
      aggressive behavior in adulthood, with its absence resulting in heightened
      aggression.

PMID- 22609340
TI  - Noninvasive cardiac output monitors: a state-of the-art review.

PMID- 22609341
TI  - A combined cultivation and cultivation-independent approach shows high bacterial
      diversity in water-miscible metalworking fluids.
AB  - Ten metalworking fluids (MWF) and seven water preparation basis samples (WPB)
      were taken from five industrial plants in Germany. Total cells (TCC) and colony
      forming units (CFU) were counted, strains were isolated and their 16S rRNA gene
      was sequenced. Additionally, DNA was extracted directly from the samples, and
      clone libraries of 16S rRNA genes were built and gene sequenced. TCC ranged from
      7.6*10(4) TCC/mL MWF to 1.6*10(8) TCC/mL MWF, and from 4.6*10(2) TCC/mL WPB to
      7.8*10(7) TCC/mL WPB. The CFU showed similar but often lower results. A total of
      70 isolates and 732 clones were 16S rRNA gene sequenced and all isolates, as well
      as 183 of the nearly full length 16S rRNA of these clones, were gene sequenced. A
      total of 98 different genera were detected in all 17 samples. The number of
      genera within each sample varied highly, with 1-22 genera per sample. The
      dominant genera in MWF were Leucobacter, Desemzia, Sphingomonas and Wautersiella.
      From these, only Sphingomonas was detected in WPB as well. This study showed that
      MWF can harbour a high bacterial diversity, which differs significantly from the
      bacterial flora of the corresponding WPB.

PMID- 22609342
TI  - Diazotrophic Burkholderia species isolated from the Amazon region exhibit
      phenotypical, functional and genetic diversity.
AB  - Forty-eight Burkholderia isolates from different land use systems in the Amazon
      region were compared to type strains of Burkholderia species for phenotypic and
      functional characteristics that can be used to promote plant growth. Most of
      these isolates (n=46) were obtained by using siratro (Macroptilium atropurpureum 
      44) and common bean (Phaseolus vulgaris - 2) as the trap plant species; two
      isolates were obtained from nodules collected in the field from Indigofera
      suffruticosa and Pithecellobium sp. The evaluated characteristics were the
      following: colony characterisation on "79" medium, assimilation of different
      carbon sources, enzymatic activities, solubilisation of phosphates, nitrogenase
      activity and antifungal activity against Fusarium oxysporium f. sp. phaseoli.
      Whole cell protein profiles, 16S rRNA, gyrB, and recA gene sequencing and
      multilocus sequence typing were used to identify the isolates. The isolates
      showed different cultural and biochemical characteristics depending on the legume
      species from which they were obtained. Except for one isolate from I.
      suffruticosa, all isolates were able to solubilise calcium phosphate and present
      nitrogenase activity under free-living conditions. Only one isolate from common
      beans, showed antifungal activity. The forty four isolates from siratro nodules
      were identified as B. fungorum; isolates UFLA02-27 and UFLA02-28, obtained from
      common bean plants, were identified as B. contaminans; isolate INPA89A, isolated
      from Indigofera suffruticosa, was a close relative of B. caribensis but could not
      be assigned to an established species; isolate INPA42B, isolated from
      Pithecellobium sp., was identified as B. lata. This is the first report of
      nitrogenase activity in B. fungorum, B. lata and B. contaminans.

PMID- 22609343
TI  - Anterior retropharyngeal approach for ventral perimedullary arteriovenous fistula
      (PMAVF) in upper cervical spine: preliminary report.

PMID- 22609344
TI  - Pannus regression after posterior decompression and occipito-cervical fixation in
      occipito-atlanto-axial instability due to rheumatoid arthritis: case report and
      literature review.
AB  - OBJECTIVES: Several techniques have been proposed for treating cervical spine
      instability due to rheumatoid arthritis. The aim of this study was to screen the
      different treatment options used in this pathology to evaluate the best form of
      treatment when the progression of rheumatoid disease affected the cranio
      vertebral junction (CVJ) stability. The most important purpose of this study was
      to achieve both the efficacy of occipito-cervical fusion (OCF) to stabilize the
      occipitocervical junction and stop pannus progression. The authors describe their
      case example and stress, in the light of a literature review, the hypothesis that
      a stable biomechanical system extended to all the spaces involved, has both
      direct and indirect effects on RA pannus progression and the condition
      responsible for its formation, such as inflammation and articular hypermobility.
      Hence, the aim of this study is to advance this thesis, which may be extended to
      a wider statistical sample, with the same characteristics. METHOD: A systematic
      literature research of case report articles, review articles, original articles,
      and prospective cohort studies, published from 1978 to 2011, was performed using
      PUBMED to analyze the different surgical strategies of RA involving CVJ and the
      role of OCF in these conditions. The key words used for the search the were:
      "inflammatory cervical pannus regression", "rheumatoid arthritis of the cranio
      cervical junction", "occipito-cervical fusion", "treatment option in rheumatoid
      cervical instability", "altanto-axial dislocation", "craniovertebral junction"
      and "surgical technique". In addition, the authors reported their experience in a
      patient affected by erosive rheumatoid arthritis (ERA) with an anterior and
      posterior pannus involving C0-C1-C2. They decided to report this exemplative case
      to emphasize their own assumptions concerning the association between a posterior
      bony fusion, the arrest of anterior pannus progression and the improvement of
      functional outcome, without, however, a direct intervention on the anterior
      pannus. RESULT: Thirty-seven different studies were identified that reflected
      search criteria, five of which were literature reviews. The different surgical
      treatment options in cervical RA disease are described in relation to
      neurological outcome according to the Ranawat grading system, functional outcome
      or quality of life according to the Steinbrocker classification, and progression
      of cervical instability and radiographic index of cranial settling, focusing on
      the role of OCF.

PMID- 22609345
TI  - Prostaglandin transporter modulates wound healing in diabetes by regulating
      prostaglandin-induced angiogenesis.
AB  - Prostaglandin transporter (PGT) mediates prostaglandin (PG) catabolism and PG
      signal termination. The prostanoid PGE(2), which induces angiogenesis and
      vasodilation, is diminished in diabetic skin, suggesting that PGT up-regulation
      could be important in wound healing deficiency, typified by diabetic foot ulcer.
      We hypothesized that up-regulation of PGT in hyperglycemia could contribute to
      weakened PGE(2) signaling, leading to impaired angiogenesis and wound healing. In
      human dermal microvascular endothelial cells (HDMECs), exposure to hyperglycemia
      increased PGT expression and activity up to threefold, accompanied by reduced
      levels of PGE(2). Hyperglycemia reduced HDMEC migration by 50% and abolished tube
      formation. Deficits in PGE(2) expression, HDMEC migration, and tube formation
      could be corrected by treatment with the PGT inhibitor T26A, consistent with the
      idea that PGT hyperactivity is responsible for impairments in angiogenesis
      mediated by PG signaling. In vivo, PGT expression was profoundly induced in
      diabetes and by wounding, correlating with diminished levels of proangiogenic
      factors PGE(2) and VEGF in cutaneous wounds of diabetic mice. Pharmacological
      inhibition of PGT corrected these deficits. PGT inhibition shortened cutaneous
      wound closure time in diabetic mice from 22 to 16 days. This effect was
      associated with increased proliferation, re-epithelialization,
      neovascularization, and blood flow. These data provide evidence that
      hyperglycemia enhances PGT expression and activity, leading to diminished
      angiogenic signaling, a possible key mechanism underlying defective wound healing
      in diabetes.

PMID- 22609346
TI  - Myelopathy secondary to copper deficiency as a complication of treatment of
      Wilson's disease.
AB  - Wilson's Disease (WD) is an autosomal recessive disorder of copper metabolism
      resulting in a pathological accumulation of this metal, initially in the liver
      and later in other organs, mainly brain. Treatment with copper chelating agents
      and zinc salts results in a depletion of copper deposits and prevents or reverses
      the clinical manifestations. Copper deficiency may cause haematological and
      neurological changes, the latter principally being polyneuropathy and myelopathy.
      We report a patient with WD who developed a myelopathy associated with a
      deficiency of copper following prolonged treatment with D-penicillamine and zinc
      salts.

PMID- 22609347
TI  - [Portal vein thrombosis associated with biliary tract infection].
AB  - OBJECTIVE: To describe the etiology, symptoms and management of portal vein
      thrombosis associated with biliary tract infection and to compare our findings
      with classical causes of pylephlebitis. MATERIAL AND METHODS: We performed a
      retrospective descriptive study of 10 patients in a tertiary hospital. RESULTS:
      Portal vein thrombosis was associated with biliary tract infection in seven
      patients and with classical causes of pylephlebitis in three. In both groups,
      symptoms consisted of fever and abdominal pain accompanied by leukocytosis and
      increased liver enzymes. Blood cultures were positive in most patients and the
      main complication was liver abscess. The therapeutic management and outcomes were
      similar in both groups. CONCLUSIONS: Portal vein thrombosis can be associated
      with biliary tract infection. Clinical presentation and outcomes are highly
      similar to those in classical causes of pylephlebitis.

PMID- 22609348
TI  - Membrane adsorption and binding, cellular uptake and cytotoxicity of cell
      penetrating peptidomimetics with alpha-peptide/beta-peptoid backbone: effects of
      hydrogen bonding and alpha-chirality in the beta-peptoid residues.
AB  - Cell-penetrating peptides (CPPs) provide a promising approach for enhancing
      intracellular delivery of therapeutic biomacromolecules by increasing transport
      through membrane barriers. Here, proteolytically stable cell-penetrating
      peptidomimetics with alpha-peptide/beta-peptoid backbone were studied to evaluate
      the effect of alpha-chirality in the beta-peptoid residues and the presence of
      guanidinium groups in the alpha-amino acid residues on membrane interaction. The
      molecular properties of the peptidomimetics in solution (surface and
      intramolecular hydrogen bonding, aqueous diffusion rate and molecular size) were
      studied along with their adsorption to lipid bilayers, cellular uptake, and
      toxicity. The surface hydrogen bonding ability of the peptidomimetics reflected
      their adsorbed amounts onto lipid bilayers as well as with their cellular uptake,
      indicating the importance of hydrogen bonding for their membrane interaction and
      cellular uptake. Ellipsometry studies further demonstrated that the presence of
      chiral centers in the beta-peptoid residues promotes a higher adsorption to
      anionic lipid bilayers, whereas circular dichroism results showed that alpha
      chirality influences their overall mean residue ellipticity. The presence of
      guanidinium groups and alpha-chiral beta-peptoid residues was also found to have
      a significant positive effect on uptake in living cells. Together, the findings
      provide an improved understanding on the behavior of cell-penetrating
      peptidomimetics in the presence of lipid bilayers and live cells.

PMID- 22609349
TI  - Electrospun drug-eluting sutures for local anesthesia.
AB  - We have developed a local anesthetic-eluting suture system which would combine
      the function and ubiquity of the suture for surgical repair with the controlled
      release properties of a biodegradable polymeric matrix. Drug-free and drug-loaded
      poly(lactic-co-glycolic acid) (PLGA) sutures were fabricated by electrospinning,
      with or without the local anesthetic bupivacaine. The tensile strength of the
      electrospun sutures decreased as drug content increased, but strains remained
      relatively similar across all groups. Sutures released their entire drug payload
      over the course of 12 days and maintained approximately 12% of their initial
      tensile strength after 14 days of incubation in vitro. In a rat skin wound model,
      local analgesia was achieved 1 day after surgery and lasted approximately 1 week
      in 90% of treated animals (n=10, p<0.05), and all wounds were able to heal
      normally without the need for further reinforcement. The sutures caused tissue
      reaction in vivo that was comparable to that seen with a commercially available
      suture composed of PLGA. Such sutures may enhance perioperative analgesia and
      mitigate the need for standard postoperative opioid analgesics.

PMID- 22609350
TI  - Challenges in drug delivery to the brain: nature is against us.
AB  - Nanomedicine is a fast evolving field involving nanoparticles or nanostructures
      for medical applications. Especially in the underdeveloped field of drug delivery
      to the brain, there are high expectations for the ability of multifunctional
      nanoparticles (NPs) to cross the blood-brain barrier (BBB). In the present review
      the challenges nanoparticles face after injection into the body will be
      summarized. There is a broad range of biological, chemical and physical hurdles
      for NPs to reach the brain. Perhaps the most challenging task will be to design
      and develop nanoparticles that specifically target that right subset of diseased
      neurons without affecting other healthy neurons. This is of immense importance
      especially in the case of targeting toxic drugs to highly invasive brain tumors.
      Already, without the additional obstacle in the form of the BBB, targeting
      nanoparticles against a small subset of cells in the body is a big challenge.
      While the permeability of the blood vessels in other tissues is comparably higher
      the brain microvasculature is highly restrictive. The reason for this is that
      uncontrolled invasion of nano-objects or molecules may lead to a pathological
      change in neurons responsible for memory, personality, senses and movement. With
      nanomedicine we have for the first time the possibility to design systems to meet
      requirements such as reduced side-effects, controlled release, targeted delivery
      as well as higher drug bioavailability at the target site. If the brain delivery
      of drugs for neurodegenerative disease or cerebral cancer is to be successful, a
      far better understanding of the complex processes taking place on the
      nanoparticles surface, as well as in cell-NP contact with the different transit
      organs and tissues, will be required.

PMID- 22609351
TI  - Defeating Leishmania resistance to miltefosine (hexadecylphosphocholine) by
      peptide-mediated drug smuggling: a proof of mechanism for trypanosomatid
      chemotherapy.
AB  - Miltefosine (hexadecylphosphocholine, HePC), the first orally active drug
      successful against leishmaniasis, is especially active on the visceral form of
      the disease. Resistance mechanisms are almost exclusively associated to
      dysfunction in HePC uptake systems. In order to evade the requirements of its
      cognate receptor/translocator, HePC-resistant Leishmania donovani parasites (R40
      strain) were challenged with constructs consisting of an omega-thiol
      functionalized HePC analogue conjugated to the cell-penetrating peptide (CPP)
      Tat(48-60), either through a disulfide or a thioether bond. The conjugates enter
      and kill both promastigote and intracellular amastigote forms of the R40 strain.
      Intracellular release of HePC by reduction of the disulfide-based conjugate was
      confirmed by means of double tagging at both the CPP (Quasar 670) and HePC
      (BODIPY) moieties. Scission of the conjugate, however, is not mandatory, as the
      metabolically more stable thioether conjugate retained substantial activity. The
      disulfide conjugate is highly active on the bloodstream form of Trypanosoma b.
      brucei, naturally resistant to HePC. Our results provide proof-of-mechanism for
      the use of CPP conjugates to avert drug resistance by faulty drug accumulation in
      parasites, as well as the possibility to extend chemotherapy into other parasites
      intrinsically devoid of membrane translocation systems.

PMID- 22609352
TI  - Endocytic pathway rapidly delivers internalized molecules to lysosomes: an
      analysis of vesicle trafficking, clustering and mass transfer.
AB  - Lysosomes play a critical role in intracellular drug delivery. For enzyme-based
      therapies, they represent a potential target site whereas for nucleic acid or
      many protein drugs, they represent the potential degradation site. Either way,
      understanding the mechanisms and processes involved in routing of materials to
      lysosomes after cellular entry is of high interest to the field of drug delivery.
      Most therapeutic cargoes other than small hydrophobic molecules enter the cells
      through endocytosis. Endocytosed cargoes are routed to lysosomes via microtubule
      based transport and are ultimately shared by various lysosomes via tethering and
      clustering of endocytic vesicles followed by exchange of their contents. Using a
      combined experimental and numerical approach, here we studied the rates of mass
      transfer into and among the endocytic vesicles in a model cell line, 3T3
      fibroblasts. In order to understand the relationship of mass transfer with
      microtubular transport and vesicle clustering, we varied both properties through
      various pharmacological agents. At the same time, microtubular transport and
      vesicle clustering were modeled through diffusion-advection equations and the
      Smoluchowski equations, respectively. Our analysis revealed that the rate of mass
      transfer is optimally related to microtubular transport and clustering properties
      of vesicles. Further, the rate of mass transfer is highest in the innate state of
      the cell. Any perturbation to either microtubular transport or vesicle
      aggregation led to reduced mass transfer to lysosome. These results suggest that
      in the absence of an external intervention the endocytic pathway appears to
      maximize molecular delivery to lysosomes. Strategies are discussed to reduce mass
      transfer to lysosomes so as to extend the residence time of molecules in
      endosomes or late endosomes, thus potentially increasing the likelihood of their
      escape before disposition in the lysosomes.

PMID- 22609353
TI  - Porcine reproductive and respiratory syndrome virus induces CD4+CD8+CD25+Foxp3+
      regulatory T cells (Tregs).
AB  - The aim of this study was to analyze the regulatory T cells (Tregs) induced by
      the porcine reproductive and respiratory syndrome virus (PRRSV) in pigs. Serum,
      blood, tonsil, and mediastinal lymph nodes' samples were obtained at different
      time post-infection (dpi). The frequencies of CD4(+)CD8(-)CD25(+)Foxp3(+),
      CD4(+)CD8(+)CD25(+)Foxp3(+), or CD4(-)CD8(+)CD25(+)Foxp3(+) phenotypes were
      determined in PBMC and lymph node cells, and cells producing IL-10 or TGF-beta
      were analyzed. PRRSV increased the number of CD4(+)CD8(+)CD25(+)Foxp3(+) cells at
      14 dpi, whereas CD4(+)CD8(-)CD25(+)Foxp3(+) remained constant until 28 dpi.
      Positive correlation exists between viremia and induced regulatory cells.
      CD4(+)CD8(+)CD25(+)Foxp3(+)-induced Treg cells were consistently observed in
      lymphoid tissues. Analysis of IL-10- and TGF-beta-producing cell demonstrated
      that in response to PRRSV, CD4(+)CD8(-)Foxp3(low) and CD4(+)CD8(+)Foxp3(high)
      cells increase moderately the proportion of IL-10(+) cells. TGF-beta was only
      observed in the CD4(+)CD8(+)Foxp3(high) population after PRRSV stimulation. In
      conclusion, PRRSV infection increases the frequency of Tregs with the phenotype
      CD4(+)CD8(+)CD25(+)Foxp3(high) and produces TGF-beta.

PMID- 22609354
TI  - Characterization of a recombinant canine coronavirus with a distinct receptor
      binding (S1) domain.
AB  - Canine alphacoronaviruses (CCoV) exist in two serotypes, type I and II, both of
      which can cause severe gastroenteritis. Here, we characterize a canine
      alphacoronavirus, designated CCoV-A76, first isolated in 1976. Serological
      studies show that CCoV-A76 is distinct from other CCoVs, such as the prototype
      CCoV-1-71. Efficient replication of CCoV-A76 is restricted to canine cell lines,
      in contrast to the prototypical type II strain CCoV-1-71 that more efficiently
      replicates in feline cells. CCoV-A76 can use canine aminopeptidase N (cAPN)
      receptor for infection of cells, but was unable to use feline APN (fAPN). In
      contrast, CCoV-1-71 can utilize both. Genomic analysis shows that CCoV-A76
      possesses a distinct spike, which is the result of a recombination between type I
      and type II CCoV, that occurred between the N- and C-terminal domains (NTD and C
      domain) of the S1 subunit. These data suggest that CCoV-A76 represents a
      recombinant coronavirus form, with distinct host cell tropism.

PMID- 22609355
TI  - Microspherule protein 2 associates with ASK1 and acts as a negative regulator of
      stress-induced ASK1 activation.
AB  - Microspherule protein 2 (MCRS2) has been reported to associate with the cellular
      function of telomerase inhibition, transcriptional regulation and cellular
      transformation. Here, we report a novel function of MCRS2 in ASK1 pathway. We
      found that MCRS2 directly binds to ASK1 in vivo and co-localises with ASK1 in the
      cytoplasm. Overexpression of MCRS2 inhibited oxidative stress (H(2)O(2))-induced
      ASK1 activation. Knockdown of MCRS2 expression accelerated p38 and JNK
      phosphorylation and promoted apoptosis in response to H(2)O(2). Finally, H(2)O(2)
      treatment induced proteasomal degradation of MCRS2, which was further enhanced by
      activated ASK1. Our results clearly demonstrate that MCRS2 plays a negative role
      in stress-induced ASK1 activation.

PMID- 22609356
TI  - Identification of an amyloid fibril forming peptide comprising residues 46-59 of
      apolipoprotein A-I.
AB  - Apolipoprotein A-I (apoA-I) is deposited as amyloid within various major organs
      in hereditary apoA-I amyloidosis, and in arterial plaques associated with
      atherosclerosis. We have identified a tryptic fragment of apoA-I, apoA-I(46-59),
      that retains the ability to form amyloid-like fibrils with cross-beta structure.
      ApoA-I(46-59) corresponds closely to a conformationally extended segment in the
      crystal structure of apoA-IDelta(185-243) and is located in the N-terminal region
      of apoA-I, which accumulates in hereditary apoA-I amyloidosis. Our results
      provide direct experimental evidence that this region of apoA-I is amyloidogenic
      and integral to initiation and propagation of amyloid formation by the protein.

PMID- 22609357
TI  - Crosstalk between TGF-beta and hedgehog signaling in cancer.
AB  - Hedgehog (HH) and TGF-beta signals control various aspects of embryonic
      development and cancer progression. While their canonical signal transduction
      cascades have been well characterized, there is increasing evidence that these
      pathways are able to exert overlapping activities that challenge efficient
      therapeutic targeting. We herein review the current knowledge on HH signaling and
      summarize the recent findings on the crosstalks between the HH and TGF-beta
      pathways in cancer.

PMID- 22609358
TI  - Regulatory mechanism of PAC1 gene expression via Sp1 by nerve growth factor in
      PC12 cells.
AB  - In addition to VPAC1 and VPAC2, PAC1 is involved in the pleiotropic action of
      pituitary adenylate cyclase activating polypeptide (PACAP) in the CNS. A
      luciferase reporter assay for the human PAC1 gene (-2160/+268) revealed that NGF
      treatment significantly augments the promoter activity of the PAC1 gene.
      Moreover, the Sp1 site at -282/-273 was shown to be essential for the NGF
      augmented promoter activity of the PAC1 gene. Treatment with U0126, an MEK
      inhibitor, or Mithramycin A, an Sp1 inhibitor, significantly attenuated promoter
      activity. These results indicate that activation of Sp1 by the Ras/MAPK pathway
      might participate in neuron specific expression of the PAC1 gene.

PMID- 22609360
TI  - Cellular redox potential and the biomolecular electrochemical series: a systems
      hypothesis.
AB  - The role of cellular redox potential in the regulation of protein activity is
      becoming increasingly appreciated and characterized. In this paper we put forward
      a new hypothesis relating to redox regulation of cellular physiology. We have
      exemplified our hypothesis using apoptosis since its redox phenomenology is well
      established, but believe that it is equally applicable to several other pathways.
      Our hypothesis is that since multiple proteins in the apoptosis pathway are
      thought to be regulated via oxidation/reduction reactions and since cellular
      redox potentials have been shown to become progressively more oxidative during
      apoptosis, that the proteins could be arranged in an electrochemical series where
      the protein's standard potential correlates with its position in the pathway.
      Since the most stable oxidation state of the protein is determined by its
      standard potential and the redox potential of its environment (in a way
      predictable by the Nernst equation), a quantitative model of the redox regulation
      of the pathway could be developed. We have outlined our hypothesis, illustrating
      it using a pathway map which assembles a selection of the literature on apoptosis
      into a readable graphical format. We have also outlined experimental approaches
      suitable for testing our hypothesis.

PMID- 22609359
TI  - Puerarin inhibits the retinal pericyte apoptosis induced by advanced glycation
      end products in vitro and in vivo by inhibiting NADPH oxidase-related oxidative
      stress.
AB  - Retinal pericyte loss is one of the histopathological hallmarks of early diabetic
      retinopathy. Puerarin (4'-7-dihydroxy-8-beta-d-glucosylisoflavone), which is an
      isoflavone-C-glucoside, causes various pharmacological effects that include
      antihyperglycemic and anti-inflammatory activities. In the present study, we
      determined the efficacy and possible mechanism of puerarin on the advanced
      glycation end product (AGE)-modified bovine serum albumin (BSA)-induced apoptosis
      of cultured bovine retinal pericytes and rat retinal pericytes in intravitreally
      AGE-modified rat serum albumin (RSA)-injected eyes. Puerarin significantly
      inhibited pericyte apoptosis, the generation of reactive oxygen species (ROS),
      and NADPH oxidase activity by inhibiting the phosphorylation of p47phox and Rac1
      which were induced by the AGE-BSA treatment. The puerarin treatment markedly
      suppressed the activation of nuclear factor-kappaB (NF-kappaB). In addition, the
      in vivo apoptosis of the retinal pericyte of rats that was stimulated by the
      intravitreal injection of AGE-RSA was evidently attenuated by the puerarin
      treatment. These results demonstrate that puerarin may exert inhibitory effects
      on AGE-induced pericyte apoptosis by interfering with the NADPH oxidase-related
      ROS pathways and blocking NF-kappaB activation, thereby ameliorating retinal
      microvascular dysfunction.

PMID- 22609361
TI  - Prefrontal serotonin depletion impairs egocentric, but not allocentric working
      memory in rats.
AB  - Working memory is a cognitive ability chiefly organized by the prefrontal cortex.
      Working memory tests may be resolved based on allocentric or egocentric spatial
      strategies. Serotonergic neurotransmission is closely involved in working memory,
      but its role in spatial strategies for working memory performance is unknown. To
      address this issue, prefrontal serotonin depletion was induced to adult male
      rats, and three days after the behavioral expression of both allocentric and
      egocentric strategies were evaluated in the "Y" maze and in a crossed-arm maze,
      respectively. Serotonin depletion caused no effects on allocentric-related
      behavioral performance, but lesioned rats performed deficiently when the
      egocentric working memory was evaluated. These results suggest that serotonin may
      be more closely related with the organization of working memory that uses own
      movement-guided responses than with that involving the use of external
      visuospatial signals. Further neurochemical studies are needed to elucidate
      possible interactions between serotonergic activity and other neurotransmitter
      systems in the organization of working memory-related allocentric and egocentric
      strategies.

PMID- 22609362
TI  - Differential expression of immune genes of adult honey bee (Apis mellifera) after
      inoculated by Nosema ceranae.
AB  - Nosema ceranae is a microsporidium parasite infecting adult honey bees (Apis
      mellifera) and is known to affects at both the individual and colony level. In
      this study, the expression levels were measured for four antimicrobial peptide
      encoding genes that are associated with bee humoral immunity (defensin, abaecin,
      apidaecin, and hymenoptaecin), eater gene which is a transmembrane protein
      involved cellular immunity and gene encoding female-specific protein
      (vitellogenin) in honey bees when inoculated by N. ceranae. The results showed
      that four of these genes, defensin, abaecin, apidaecin and hymenoptaecin were
      significantly down-regulated 3 and 6days after inoculations. Additionally,
      antimicrobial peptide expressions did not significantly differ between control
      and inoculated bees after 12days post inoculation. Moreover, our results revealed
      that the mRNA levels of eater and vitellogenin did not differ significantly
      following N. ceranae inoculation. Therefore, in this study we reaffirmed that N.
      ceranae infection induces host immunosuppression.

PMID- 22609363
TI  - DNA replication events during larval silk gland development in the silkworm,
      Bombyx mori.
AB  - The silk gland is an important organ in silkworm as it synthesizes silk proteins
      and is critical to spinning. The genomic DNA content of silk gland cells
      dramatically increases 200-400 thousand times for the larval life span through
      the process of endomitosis. Using in vitro culture, DNA synthesis was measured
      using BrdU labeling during the larval molt and intermolt periods. We found that
      the cell cycle of endomitosis was activated during the intermolt and was
      inhibited during the molt phase. The anterior silk gland, middle silk gland, and
      posterior silk gland cells asynchronously exit the endomitotic cycle after day 6
      in 5th instar larvae, which correlated with the reduced expression of the cell
      cycle-related cdt1, pcna, cyclin E, cdk2 and cdk1 mRNAs in the wandering phase.
      Additional starvation had no effect on the initiation of silk gland DNA synthesis
      of the freshly ecdysed larvae.

PMID- 22609364
TI  - A new look at the comparative physiology of insect and human hearts.
AB  - Recent electrocardiographic (ECG) studies of insect hearts revealed the presence
      of human-like, involuntary and purely myogenic hearts. Certain insects, like a
      small light-weight species of hoverfly (Episyrphus balteatus), have evolved a
      very efficient cardiac system comprised of a compact heart ventricle and a narrow
      tube of aorta, which evolved as an adaptation to sustained hovering flights.
      Application of thermocardiographic and optocardiographic ECG methods revealed
      that adult flies of this species use the compact muscular heart chamber (heart
      ventricle) for intensive pumping of insect "blood" (haemolymph) into the head and
      thorax which is ringed all over with indirect flight musculature. The recordings
      of these hearts revealed extremely high, record rates of forward-directed,
      anterograde heartbeat (up to 10Hz), associated with extremely enhanced synchronic
      (not peristaltic) propagation of systolic myocardial contractions (32.2mm/s at
      room temperature). The relatively slow, backward-directed or retrograde cardiac
      contractions occurred only sporadically in the form of individual or twinned
      pulses replacing occasionally the resting periods. The compact heart ventricle
      contained bi-directional lateral apertures, whose opening and closure diverted
      the intracardiac anterograde "blood" streams between the abdominal haemocoelic
      cavity and the aortan artery, respectively. The visceral organs of this flying
      machine (crop, midgut) exhibited myogenic, extracardiac peristaltic pulsations
      similar to heartbeat, including the periodically reversed forward and backward
      direction of the peristaltic waves. The tubular crop contracted with a
      periodicity of 1Hz, both forwards and backwards, with propagation of the
      peristaltic waves at 4.4mm/s. The air-inflated and blindly ended midgut
      contracted at 0.2Hz, with a 0.9mm/s propagation of the peristaltic contraction
      waves. The neurogenic system of extracardiac haemocoelic pulsations, widely
      engaged in the regulation of circulatory and respiratory functions in other
      insect species, has been replaced here by a more economic, myogenic pulsation of
      the visceral organs as a light-weight evolutionary adaptation to prolonged
      hovering flight. Striking structural, functional and even genetic similarities
      found between the hearts of Episyrphus, Drosophila and human hearts, have been
      practically utilised for inexpensive testing of new cardioactive or
      cardioinhibitory drugs on insect heart.

PMID- 22609365
TI  - Quantitative assessment of forward and backward second harmonic three dimensional
      images of collagen Type I matrix remodeling in a stimulated cellular environment.
AB  - The structural remodeling of collagens is important in several biological
      processes including wound healing, tendon repair and adaptation, fibrosis and
      morphogenesis. Multiphoton microscopy is efficient in the induction of highly
      specific second harmonic generation (SHG) signal from non-centrosymmetric
      macromolecules such as fibrillar collagens. Although the detectors in the
      reflection geometry have been normally employed for capturing the backward
      scattered SHG considering the wide range of engineered thick tissue applications,
      there are still questions about the generated 3D collagen structures because of
      the directional pattern of SHG signals. The present study dealt with an in vitro
      collagen-fibroblast raft or bioartificial tendon model where the stimulation of
      fibroblast cells induced lateral orientation of collagen Type I fibers. The SHG
      signals originating from 3D collagen matrix were captured simultaneously in both
      forward and backward scattering directions. Our structural analysis indicates
      that collagen fibers formed in such in vitro model systems are predominantly of
      uniform sizes and are aligned preferentially in the lateral direction. The criss
      cross arrangements of laterally oriented fibers are evident in the initial stages
      of contraction but eventually those laterally oriented collagen fibers are found
      to be aligned in parallel to each other as well as to the fibroblasts after an
      extended period of contraction. Our comprehensive quantitative assessment of
      simultaneously captured forward and backward 3D SHG image datasets, which
      includes the SHG signal decay, fiber diameter, cell dimensions, colocalization
      profiles, the 3D voxel volumes and Fourier analysis, indicates strong correlation
      of structural features identified in forward and backward directions.

PMID- 22609366
TI  - Neurotrophic tyrosine kinase polymorphism impacts white matter connections in
      patients with major depressive disorder.
AB  - BACKGROUND: Polymorphisms in the brain-derived neurotrophic factor (BDNF) gene
      and its receptor neurotrophic tyrosine kinase receptor type 2 (NTRK2) have been
      implicated in mood disorders. The aim of this study was to examine whether the
      NTRK2 and BDNF polymorphisms impact brain white matter connections in major
      depressive disorder and whether they may also have an interactive effect with
      environmental stress in the form of early life adversity. METHODS: The study
      group comprised 45 depressed patients and 45 age- and gender-matched control
      subjects. High angular resolution diffusion images were obtained and analyzed
      using tract-based spatial statistics. Analysis of a single nucleotide
      polymorphism in the BDNF (rs6265/Valine66Methionine) and NTRK2 (rs11140714) genes
      was performed. RESULTS: An interactive effect was found between NTRK2 and
      depression diagnosis maximally affecting the cingulum. Depressed patients
      homozygous for the A allele of NTRK2 showed significantly reduced fractional
      anisotropy compared with depressed patients with at least one copy of the G
      allele or control subjects with either the A/A or G carrier genotypes in the left
      and right corona radiata, left uncinate fasciculus, left inferior fronto
      occipital fasciculus, left cerebral peduncle, posterior thalamic radiation, and
      middle cerebral peduncle. Significantly smaller gray matter volume was seen in
      frontal lobe regions in patients homozygous for the A allele. CONCLUSIONS:
      Polymorphisms in NTRK2 gene increase risk of architectural changes in several
      brain regions involved in emotional regulation.

PMID- 22609368
TI  - Progesterone and ovarian stimulation control endometrial pinopode expression
      before implantation in mice.
AB  - Endometrial epithelial pinopodes are considered as markers of endometrial
      receptivity and seem to be directly involved in the adhesion of the blastocysts
      to the endometrial surface. The aim of the study was to assess the effects of
      ovarian stimulation and progesterone injection on pinopode expression, and
      compare morphological characteristics in the preimplantation stage in mice. Adult
      female mice (n=30) were divided into three groups: control, superovulated and
      superovulated-progesterone injected. In experimental groups the mice received
      7.5I.U human menopausal gonadotropin (HMG) and then after 48h 7.5I.U human
      chorionic gonadotropic (HCG) hormone. After that every two females were put with
      one male in one cage for mating. Superovulated-progesterone group were injected
      with progesterone (1mg/mouse) in 24, 48, 72h interval after the HMG injection.
      Animals were sacrificed in 96h after HMG injection, and their uterines (the
      middle one-third) were prepared for transmission electron microscope studies.
      That demonstrated that all groups differed from each other. In most of the
      controls and hyperstimulated-progesterone mice 4 days after HMG injection, long
      and short microvilli were seen, but they had no developed pinopodes, while in
      hyperstimulated mice, well developed pinopodes were expressed 4 days after HMG
      injection. IN CONCLUSION: hyperstimulated mice without progesterone injection may
      be useful for the studies of pinopodes and implantation.

PMID- 22609367
TI  - Distinct age-dependent effects of methylphenidate on developing and adult
      prefrontal neurons.
AB  - BACKGROUND: Methylphenidate (MPH) has long been used to treat attention
      deficit/hyperactivity disorder (ADHD); however, its cellular mechanisms of action
      and potential effects on prefrontal cortical circuitry are not well understood,
      particularly in the developing brain system. A clinically relevant dose range for
      rodents has been established in the adult animal; however, how this range will
      translate to juvenile animals has not been established. METHODS: Juvenile
      (postnatal day [PD] 15) and adult (PD90) Sprague Dawley rats were treated with
      MPH or saline. Whole-cell patch clamp recording was used to examine the neuronal
      excitability and synaptic transmission in pyramidal neurons of prefrontal cortex.
      Recovery from MPH treatment was also examined at 1, 5, and 10 weeks following
      drug cessation. RESULTS: A dose of 1 mg/kg intraperitoneal MPH, either single
      dose or chronic treatment (well within the accepted therapeutic range for
      adults), produced significant depressive effects on pyramidal neurons by
      increasing hyperpolarization-activated currents in juvenile rat prefrontal
      cortex, while exerting excitatory effects in adult rats. Minimum clinically
      relevant doses (.03 to .3 mg/kg) also produced depressive effects in juvenile
      rats, in a linear dose-dependent manner. Function recovered within 1 week from
      chronic 1 mg/kg treatment, chronic treatment with 3 and 9 mg/kg resulted in
      depression of prefrontal neurons lasting 10 weeks and beyond. CONCLUSIONS: These
      results suggest that the juvenile prefrontal cortex is supersensitive to
      methylphenidate, and the accepted therapeutic range for adults is an overshoot.
      Juvenile treatment with MPH may result in long-lasting, potentially permanent,
      changes to excitatory neuron function in the prefrontal cortex of juvenile rats.

PMID- 22609369
TI  - The complexity of virus systems: the case of endosymbionts.
AB  - Host-microbe symbioses involving bacterial endosymbionts comprise some of the
      most intimate and long-lasting interactions on the planet. While restricted gene
      flow might be expected due to their intracellular lifestyle, many endosymbionts,
      especially those that switch hosts, are rampant with mobile DNA and
      bacteriophages. One endosymbiont, Wolbachia pipientis, infects a vast number of
      arthropod and nematode species and often has a significant portion of its genome
      dedicated to prophage sequences of a virus called WO. This phage has challenged
      fundamental theories of bacteriophage and endosymbiont evolution, namely the
      phage Modular Theory and bacterial genome stability in obligate intracellular
      species. WO has also opened up exciting windows into the tripartite interactions
      between viruses, bacteria, and eukaryotes.

PMID- 22609370
TI  - Screening and analyzing potential hepatotoxic compounds in the ethanol extract of
      Asteris Radix by HPLC/DAD/ESI-MS(n) technique.
AB  - A refined toxic fraction, Fr-2, from the ethanol extract of Aster tataricus roots
      was obtained by a toxic tracing isolation. The hepatotoxic effects of Fr-2 were
      proved by the level elevation of alanine aminotransferase (ALT), aspartate
      aminotransferase (AST) and alkaline phosphatase (ALP) in mice serum and further
      confirmed by the histopathological examination on mice liver. A simple method was
      developed for qualitative analysis of constituents in Fr-2 fraction by high
      performance liquid chromatography with diode array detection (HPLC-DAD) and
      electrospray ionization tandem mass spectrometry (ESI-MS(n)). As a result, 35
      compounds were detected and identified in Fr-2. Among them, 28 compounds are
      pentapeptides, including 18 cyclic and 10 linear ones, and the sum of their peak
      area occupied about 87% (71.2% for cyclic and 15.8% for linear) of total area of
      chromatographic peak. Other 7 compounds are phenols, occupied about 5.9% of total
      area of chromatographic peak. Moreover, the structures of 10 cyclic and 2 linear
      peptides were reported for the first time. The results suggested that the
      peptides, especially the cyclic ones, are probably the principal toxic substances
      in Fr-2 also in A. tataricus roots.

PMID- 22609371
TI  - Seawater induces apoptosis in alveolar epithelial cells via the Fas/FasL-mediated
      pathway.
AB  - Our previous study showed that seawater can cause lung tissue cell apoptosis; in
      the present study, the immunohistochemistry and Western blot analysis results
      demonstrated that Fas, FasL, and cleaved caspase-8 and caspase-3 were up
      regulated in the rat lungs exposed to seawater. We found that seawater-induced
      human lung alveolar epithelial A549 cell apoptosis was concentration and time
      dependent. Moreover, seawater increased the expression of Fas, FasL, and cleaved
      caspase-8 and caspase-3 in A549 cells. The incubation of A549 cells in the
      presence of FasL-neutralising antibody (NOK-2) or caspase-8 inhibitor (Z-IETD
      FMK) resulted in a decrease of seawater-induced cell apoptosis. NOK-2 inhibited
      Fas/FasL interaction and reduced the cleavage of caspase-8 and caspase-3, and Z
      IETD-FMK blocked caspase-8 and caspase-3 activation. Seawater similarly produced
      a significant increase in rat alveolar type II cell apoptosis and expression of
      Fas and cleaved caspase-8. In summary, the Fas/FasL pathway involved in alveolar
      epithelial cell (AEC) apoptosis could be important in the pathogenesis of
      seawater-induced acute lung injury (SW-ALI).

PMID- 22609372
TI  - Label-free epitope binning assays of monoclonal antibodies enable the
      identification of antigen heterogeneity.
AB  - Label-free biosensors are often used in the discovery of therapeutic antibodies
      to characterize the epitope binding regions of a panel of monoclonal antibodies
      that target a specific antigen, thus facilitating their organization into epitope
      groups or "bins". When tested in a pairwise combinatorial manner, two antibodies
      that compete with one another for binding to a specific antigen may be grouped
      into the same epitope bin - that is, they recognize similar or overlapping
      epitopes - whereas two antibodies that bind simultaneously to the antigen are
      placed into different epitope bins. However, depending on the assay format used,
      results from such experiments can sometimes contradict one another. Here, we
      provide two examples that illustrate how antigen heterogeneity, either inherent
      in an antigen sample, or induced by the assay conditions, can confound the
      interpretation of epitope binning results and, in some cases, lead to erroneous
      conclusions. We highlight why assays that employ solution antigen are often more
      reliable than those that employ immobilized antigen and, by corroborating our
      binning results with assays that utilize native antigen, we determine which
      subpopulations of our heterogeneous antigen samples are biologically relevant and
      thus improve the correlation between epitope bins and functional activity.
      Furthermore, we provide recommendations for performing definitive binning assays
      and a diagnostic assay procedure that can be followed when antigen heterogeneity
      is suspected.

PMID- 22609373
TI  - miRSeqNovel: an R based workflow for analyzing miRNA sequencing data.
AB  - We present miRSeqNovel, an R based workflow for miRNA sequencing data analysis.
      miRSeqNovel can process both colorspace (SOLiD) and basespace (Illumina/Solexa)
      data by different mapping algorithms. It finds differentially expressed miRNAs
      and gives conservative prediction of novel miRNA candidates with customized
      parameters. miRSeqNovel is freely available at
      http://sourceforge.net/projects/mirseq/files.

PMID- 22609374
TI  - Rosiglitazone treatment reduces hippocampal neuronal damage possibly through
      alleviating oxidative stress in chronic cerebral hypoperfusion.
AB  - Oxygen free radicals and lipid peroxidation may play significant roles in the
      progress of injury induced by chronic cerebral hypoperfusion of the central
      nervous system. Rosiglitazone, a well known activator of PPARgamma, has
      neuroprotective properties in various animal models of acute central nervous
      system damage. In the present study, we evaluate the possible impact of
      rosiglitazone on chronic cerebral hypoperfused-rats in regard to the levels of
      oxidative stress, reduced glutathione, and hippocampal neuronal damage. Chronic
      cerebral hypoperfusion was generated by permanent ligation of both common carotid
      arteries of Wistar rats for one month. Animals in treatment group were given
      rosiglitazone orally at doses of 1.5, 3, or 6mg/kg per day of the 1month
      duration. The treatment significantly lowered the levels of both malondialdehyde
      and neuronal damage, while elevated the reduced glutathione level markedly. These
      findings suggest that the beneficial effect of rosiglitazone on hypoperfusion
      induced hippocampal neuronal damage might be the result of inhibition of
      oxidative insult.

PMID- 22609375
TI  - Renin inhibitor aliskiren exerts neuroprotection against amyloid beta-peptide
      toxicity in rat cortical neurons.
AB  - Accumulation of amyloid beta-peptide (Abeta) in senile plaques, a pathological
      hallmark of Alzheimer's disease (AD), has been implicated in neuronal
      degeneration. Renin-angiotensin system (RAS) blockers, including the renin
      inhibitor aliskiren, are a group of clinically relevant anti-hypertensive agents.
      The present study was initiated to investigate whether aliskiren may modulate
      Abeta neurotoxicity as an additional function aside from its established property
      of lowering blood pressure. We found aliskiren conferred neuronal resistance to
      Abeta toxicity in primary rat cortical cultures. Moreover, both Abeta25-35 and
      Abeta1-42 induced renin expression in cortical neurons; in parallel, a heightened
      expression of renin was detected in the cerebral cortices of 9-month-old AD
      transgenic mice. Notably, aliskiren blocked Abeta-mediated neuronal induction of
      renin. We therefore concluded that aliskiren may carry neuroprotective action
      against Abeta toxicity. Furthermore, the aliskiren effects may involve
      downregulation of renin expression induced by Abeta.

PMID- 22609376
TI  - Eriodictyol protects against H(2)O(2)-induced neuron-like PC12 cell death through
      activation of Nrf2/ARE signaling pathway.
AB  - Eriodictyol, a flavonoid isolated from the Chinese herb Dracocephalum rupestre
      has long been established as an antioxidant. The present study was designed to
      explore the protective effects of eriodictyol against hydrogen peroxide
      (H(2)O(2))-induced neurotoxicity with cultured rat pheochromocytoma cells (PC12
      cells) and the possible mechanisms involved. For this purpose, differentiated
      PC12 cells were cultured and exposed to 200 MUM H(2)O(2) in the absence or
      presence of eriodictyol (20, 40 and 80 MUM). In addition, the potential
      contribution of the Nrf2/ARE neuroprotective pathway in eriodictyol-mediated
      protection against H(2)O(2)-induced neurotoxicity was also investigated. The
      results showed that H(2)O(2)-induced cell death can be inhibited in the presence
      of eriodictyol as measured by assays for MTT and apoptosis. Further study
      revealed that eriodictyol induced the nuclear translocation of Nrf2, enhanced the
      expression of heme oxygenase (HO-1) and gamma-glutamylcysteine synthetase (gamma
      GCS), and increased the levels of intracellular glutathione. Treatment of PC12
      cells with Nrf2 small interference RNA abolished eriodictyol-induced HO-1 and
      gamma-GCS expression and its protective effects. In conclusion, these results
      suggest that eriodictyol upregulates HO-1 and gamma-GCS expression through the
      activation of Nrf2/ARE pathway and protects PC12 cells against H(2)O(2)-induced
      oxidative stress.

PMID- 22609377
TI  - Linkage of N-cadherin to multiple cytoskeletal elements revealed by a proteomic
      approach in hippocampal neurons.
AB  - The CNS synapse is an adhesive junction differentiated for chemical
      neurotransmission and is equipped with presynaptic vesicles and postsynaptic
      neurotransmitter receptors. Cell adhesion molecule cadherins not only maintain
      connections between pre- and postsynaptic membranes but also modulate the
      efficacy of synaptic transmission. Although the components of the cadherin
      mediated adhesive apparatus have been studied extensively in various cell
      systems, the complete picture of these components, particularly at the synaptic
      junction, remains elusive. Here, we describe the proteomic assortment of the N
      cadherin-mediated synaptic adhesion apparatus in cultured hippocampal neurons. N
      cadherin immunoprecipitated from Triton X-100-solubilized neuronal extract
      contained equal amounts of beta- and alpha-catenins, as well as F-actin-related
      membrane anchor proteins such as integrins bridged with alpha-actinin-4, and
      Na(+)/K(+)-ATPase bridged with spectrins. A close relative of beta-catenin,
      plakoglobin, and its binding partner, desmoplakin, were also found, suggesting
      that a subset of the N-cadherin-mediated adhesive apparatus also anchors
      intermediate filaments. Moreover, dynein heavy chain and LEK1/CENPF/mitosin were
      found. This suggests that internalized pools of N-cadherin in trafficking
      vesicles are conveyed by dynein motors on microtubules. In addition, ARVCF and
      NPRAP/neurojungin/delta2-catenin, but not p120ctn/delta1-catenin or plakophilins
      1, -2, -3, -4 (p0071), were found, suggesting other possible bridges to
      microtubules. Finally, synaptic stimulation by membrane depolarization resulted
      in an increased 93-kDa band, which corresponded to proteolytically truncated beta
      catenin. The integration of three different classes of cytoskeletal systems found
      in the synaptic N-cadherin complex may imply a dynamic switching of adhesive
      scaffolds in response to synaptic activity.

PMID- 22609378
TI  - Presynaptic CB(1) cannabinoid receptors control frontocortical serotonin and
      glutamate release--species differences.
AB  - Both the serotonergic and endocannabinoid systems modulate frontocortical
      glutamate release; thus they are well positioned to participate in the
      pathogenesis of psychiatric disorders. With the help of fluorescent and confocal
      microscopy, we localized the CB(1) cannabinoid receptor (CB(1)R) in VGLUT1- and 2
      (i.e. glutamatergic) and serotonin transporter- (i.e. serotonergic) -positive
      fibers and nerve terminals in the mouse and rat frontal cortex. CB(1)R activation
      by the synthetic agonists, WIN55212-2 (1 MUM) and R-methanandamide (1 MUM)
      inhibited the simultaneously measured evoked Ca(2+)-dependent release of
      [(14)C]glutamate and [(3)H]serotonin from frontocortical nerve terminals of
      Wistar rats, in a fashion sensitive to the CB(1)R antagonists, O-2050 (1 MUM) and
      LY320135 (5 MUM). CB(1)R agonists also inhibited the evoked release of
      [(14)C]glutamate in C57BL/6J mice in a reversible fashion upon washout.
      Interestingly, the evoked release of [(14)C]glutamate and [(3)H]serotonin was
      significantly greater in the CB(1)R knockout CD-1 mice. Furthermore, CB(1)R
      binding experiments revealed similar frontocortical CB(1)R density in the rat and
      the CD-1 mouse. Still, the evoked release of [(3)H]serotonin was modulated by
      neither CB(1)R agonists nor antagonists in wild-type CD-1 or C57BL/6J mice.
      Altogether, this is the first study to demonstrate functional presynaptic CB(1)Rs
      in frontocortical glutamatergic and serotonergic terminals, revealing species
      differences.

PMID- 22609380
TI  - Causality methods in cosmetovigilance: comparison of Colipa and PLM versus global
      introspection.
AB  - The European Cosmetics Regulation requires a post-marketing system for detection
      of undesirable effects on human health of cosmetic products. Colipa, the European
      Cosmetic, toiletry and perfumery association, provided guidelines for causality
      assessment of these effects. In addition another causality method originally
      designed for causality rating in Post Launch Monitoring (PLM) of novel foods has
      been employed to assess causality of cosmetic products. In this study these two
      causality schemes for consumer cosmetic products were validated against clinical
      assessment, using the method of global introspection (GI) in 100 reported cases.
      Causality assessments were performed by three experienced assessors in
      pharmacovigilance. In the event of discordance between the assessors, an adapted
      Delphi method was used. The overall Spearman correlation coefficient was 0.74 for
      comparison of Colipa versus GI, whereas this was 0.50 for PLM versus GI.
      According to current guidelines, the sensitivity was 0.95 for both the Colipa and
      PLM method, specificity was 0.84 for Colipa and 0.40 for PLM. From these results
      it can be concluded the performance of the Colipa causality method yielded better
      correlation to GI than PLM causality method. The factor identified from
      comparison of these two schemes as having greatest impact was the course of the
      reaction.

PMID- 22609381
TI  - Neuronal serotonin regulates growth of the intestinal mucosa in mice.
AB  - BACKGROUND & AIMS: The enteric abundance of serotonin (5-HT), its ability to
      promote proliferation of neural precursors, and reports that 5-HT antagonists
      affect crypt epithelial proliferation led us to investigate whether 5-HT affects
      growth and maintenance of the intestinal mucosa in mice. METHODS: cMice that lack
      the serotonin re-uptake transporter (SERTKO mice) and wild-type mice were given
      injections of selective serotonin re-uptake inhibitors (gain-of-function models).
      We also analyzed mice that lack tryptophan hydroxylase-1 (TPH1KO mice, which lack
      mucosal but not neuronal 5-HT) and mice deficient in tryptophan hydroxylase-2
      (TPH2KO mice, which lack neuronal but not mucosal 5-HT) (loss-of-function
      models). Wild-type and SERTKO mice were given ketanserin (an antagonist of the 5
      HT receptor, 5-HT(2A)) or scopolamine (an antagonist of the muscarinic receptor).
      5-HT(2A) receptors and choline acetyltransferase were localized by
      immunocytochemical analysis. RESULTS: Growth of the mucosa and proliferation of
      mucosal cells were significantly greater in SERTKO mice and in mice given
      selective serotonin re-uptake inhibitors than in wild-type mice, but were
      diminished in TPH2KO (but not in TPH1KO) mice. Ketanserin and scopolamine each
      prevented the ability of SERT knockout or inhibition to increase mucosal growth
      and proliferation. Cholinergic submucosal neurons reacted with antibodies against
      5-HT(2A). CONCLUSIONS: 5-HT promotes growth and turnover of the intestinal
      mucosal epithelium. Surprisingly, these processes appear to be mediated by
      neuronal, rather than mucosal, 5-HT. The 5-HT(2A) receptor activates cholinergic
      neurons, which provide a muscarinic innervation to epithelial effectors.

PMID- 22609382
TI  - Incidence and mortality of colorectal adenocarcinoma in persons with inflammatory
      bowel disease from 1998 to 2010.
AB  - BACKGROUND & AIMS: The relationship between inflammatory bowel disease (IBD) and
      the incidence and mortality of colorectal adenocarcinoma (CRC) has not been
      evaluated recently. METHODS: We calculated the incidence and standardized
      incidence and mortality rate ratios of CRC among adult individuals with intact
      colons using Kaiser Permanente of Northern California's database of members with
      IBD and general membership data for the period of 1998 to June 2010 (data through
      2008 were used to calculate mortality). We also evaluated trends in medication
      use and rates of cancer detection over time. RESULTS: We identified 29 cancers
      among persons with Crohn's disease (CD) and 53 among persons with ulcerative
      colitis (UC). Overall, the incidence rates of cancer among individuals with CD,
      UC, or in the general membership were 75.0, 76.0, and 47.1, respectively, per
      100,000 person-years. In the general population, the incidence of CRC was 21%
      higher in 2007-2010 than in 1998-2001 (P for trend, <.0001), coincident with the
      growth of CRC screening programs. The incidence of CRC among individuals with CD
      or UC was 60% higher than in the general population (95% confidence interval [CI]
      for CD, 20%-200%; 95% CI for UC, 30%-200%) and was stable over time (P for trend
      was as follows: CD, .98; UC, .40). During 1998-2008, the standardized mortality
      ratio for CRC in individuals with CD was 2.3 (95% CI, 1.6-3.0) and 2.0 in those
      with UC (95% CI, 1.3-2.7). Over the study period, anti-tumor necrosis factor
      agents replaced other therapies for CD and UC; the rate of colonoscopy increased
      by 33% among patients with CD and decreased by 9% in those with UC. CONCLUSIONS:
      From 1998 to 2010, the incidence of CRC in patients with IBD was 60% higher than
      in the general population and essentially stable over time.

PMID- 22609383
TI  - Validation of a simple classification system for endoscopic diagnosis of small
      colorectal polyps using narrow-band imaging.
AB  - BACKGROUND & AIMS: Almost all colorectal polyps <= 5 mm are benign, yet current
      practice requires costly pathologic analysis. We aimed to develop and evaluate
      the validity of a simple narrow-band imaging (NBI)-based classification system
      for differentiating hyperplastic from adenomatous polyps. METHODS: The study was
      conducted in 4 phases: (1) evaluation of accuracy and reliability of histologic
      prediction by NBI-experienced colonoscopists; (2) development of a classification
      based on color, vessels, and surface pattern criteria, using a modified Delphi
      method; (3) validation of the component criteria by people not experienced in
      endoscopy or NBI analysis (25 medical students, 19 gastroenterology fellows)
      using 118 high-definition colorectal polyp images of known histology; and (4)
      validation of the classification system by NBI-trained gastroenterology fellows,
      using still images. We performed a pilot evaluation during real-time colonoscopy.
      RESULTS: We developed a classification system for the endoscopic diagnosis of
      colorectal polyp histology and established its predictive validity. When all 3
      criteria were used, the specificity ranged from 94.9% to 100% and the combined
      sensitivity ranged from 8.5% to 61.0%. The specificities of the individual
      criteria were lower although the sensitivities were higher. During real-time
      colonoscopy, endoscopists made diagnoses with high confidence for 75% of
      consecutive small colorectal polyps, with 89% accuracy, 98% sensitivity, and 95%
      negative predictive values. CONCLUSIONS: We developed and established the
      validity of an NBI classification system that can be used to diagnose colorectal
      polyps. In preliminary real-time evaluation, the system allowed endoscopic
      diagnoses of colorectal polyp histology.

PMID- 22609384
TI  - Estradiol increases body weight loss and gut-peptide satiation after Roux-en-Y
      gastric bypass in ovariectomized rats.
AB  - Despite the fact that ~85% of bariatric operations are performed in women, the
      effects of the reproductive axis function on outcome of bariatric surgery remain
      to be determined. Here we developed the first published model of Roux-en-Y
      gastric bypass (RYGB) in female rats. We show in ovariectomized rats receiving
      estradiol or control treatment that (1) RYGB-induced body weight loss and (2) the
      satiating efficacy of endogenous glucagon-like peptide-1 and cholecystokinin
      satiation were significantly increased in estradiol-treated rats. These data are
      relevant to the care of obese women, in particular perimenopausal women,
      undergoing bariatric surgery.

PMID- 22609386
TI  - Tantalum (oxy)nitrides nanotube arrays for the degradation of atrazine in vis
      Fenton-like process.
AB  - In order to overcome the limitation of the application of nanoparticles, tantalum
      (oxy)nitrides nanotube arrays on a Ta foil were synthesized and introduced in vis
      (visible light)-Fenton-like system to enhance the degradation of atrazine. At
      first, the anodization of tantalum foil in a mild electrolyte solution containing
      ethylene glycol and water (v:v=2:1) plus 0.5wt.% NH(4)F produced tantala
      nanotubes with an average diameter of 30nm and a length of approximately 1MUm.
      Then the nitridation of tantala nanotube arrays resulted in the replacement of N
      atoms to O atoms to form tantalum (oxy)nitrides (TaON and Ta(3)N(5)), as
      testified by XRD and XPS analyses. The synthesized tantalum (oxy)nitrides
      nanotubes absorb well in the visible region up to 600nm. Under visible light,
      tantalum (oxy)nitrides nanotube arrays were catalytically active for Fe(3+)
      reduction. With tantalum (oxy)nitrides nanotube arrays, the degradation of
      atrazine and the formation of the intermediates in vis/Fe(3+)/H(2)O(2) system
      were significantly accelerated. This was explained by the higher concentration of
      Fe(2+) and thus the faster decomposition of H(2)O(2) with tantalum (oxy)nitrides
      nanotubes. In addition, tantalum (oxy)nitrides nanotubes exhibited stable
      performance during atrazine degradation for three runs. The good performance and
      stability of the tantalum (oxy)nitrides nanotubes film with the convenient
      separation, suggest that this film is a promising catalyst for vis-Fenton-like
      degradation.

PMID- 22609387
TI  - Simultaneous adsorption and dechlorination of 2,4-dichlorophenol by Pd/Fe
      nanoparticles with multi-walled carbon nanotube support.
AB  - Nanoscale Pd/Fe particles were combined with multi-walled carbon nanotubes
      (MWNTs) to prepare supported particles (MWNT-stabilized Pd/Fe), which were used
      to remove 2,4-dichlorophenol (2,4-DCP). The adsorption capacity of MWNTs was
      found to be increased with the increasing amount of chlorine atoms, and the
      removal rates of phenol (P), 2-chlorophenol (2-CP), 4-chlorophenol (4-CP) and 2,4
      DCP reached 19.7%, 60.5%, 72.0% and 95.1% respectively, in 1min by MWNTs due to
      pi-pi interaction. The adsorption kinetics and adsorption isotherm were also
      discussed. MWNTs as a supporter, was effective for avoiding the agglomeration of
      nZVI. Furthermore, the speedy removal efficiency of the initial substances (2,4
      DCP) reached about 50% in 1min, and over the time continued to rise to 100%,
      remaining low concentrations (<1mg L(-1)) of the intermediate substances (o-CP, p
      CP), and gradual release of the final substance (P) from MWNT-stabilized Pd/Fe
      composites during the whole process, proposed a novel method for in situ
      remediation technology.

PMID- 22609385
TI  - Increased risk for persistent intestinal metaplasia in patients with Barrett's
      esophagus and uncontrolled reflux exposure before radiofrequency ablation.
AB  - BACKGROUND & AIMS: Radiofrequency ablation (RFA) is a safe alternative to
      esophagectomy for patients with dysplastic Barrett's esophagus (BE). Although
      some studies have indicated that RFA is effective at eradicating dysplasia, most
      have found that RFA is not as effective in eradicating intestinal metaplasia. We
      investigated whether uncontrolled reflux is associated with persistent intestinal
      metaplasia after RFA. METHODS: Thirty-seven patients with BE underwent RFA, high
      resolution manometry, and 24-hour impedance-pH testing; they received proton pump
      inhibitors twice daily. Patients returned every 2 months for repeat treatment or
      standard surveillance. Patients were classified as complete responders (CRs) if
      all intestinal metaplasia was eradicated in fewer than 3 ablation sessions. We
      analyzed clinical parameters to identify factors associated with a CR or
      incomplete responder (ICR). RESULTS: Among the 37 patients, 22 had a CR and 15
      had an ICR. Mann-Whitney U tests revealed that length of BE, size of hiatal
      hernia, and frequency of reflux, but not acid reflux, differed between CRs and
      ICRs. CRs had fewer weakly acidic events than ICRs (29.5 vs 52; P < .05) and
      total reflux events (33.5 vs 60; P < .05), and a trend toward fewer weakly
      alkaline events (1.0 vs 5.0; P = .06). No other clinical or manometric features
      differed between groups. CONCLUSIONS: Uncontrolled, predominantly weakly acidic
      reflux despite twice-daily proton pump inhibitor therapy before RFA increases the
      incidence of persistent intestinal metaplasia after ablation in patients with BE.
      Length of BE and size of hiatal hernia also were associated with persistent
      intestinal metaplasia after RFA.

PMID- 22609388
TI  - Combined ultrasound/ozone degradation of carbazole in APG1214 surfactant
      solution.
AB  - We examined the effects of power and treatment time on the ultrasonically
      enhanced ozonation of carbazole dissolved in APG(1214) surfactant solutions,
      including an analysis of the mechanism of OH radical formation, the zeta
      potential of the colloidal suspension, the influence of ultrasound on micellar
      morphology, and the degradation kinetics for carbazole and APG(1214). A 30min
      ultrasound treatment at 28kHz and 20W improved the degradation of carbazole by 5
      10%, while power levels of 40W and 80W provided improvements only during the
      first 5min and resulted in reduced degradation after 15min. The OH concentration
      was inversely proportional to ultrasound power, and directly proportional to the
      irradiation time. The absolute value of the APG(1214) micelle zeta potential was
      inversely proportional to power and decreased with increasing irradiation time.
      The relationships of OH radical concentration in APG(1214) micelles, the zeta
      potential, and the micellar dynamic radius (R(h)) to ultrasonic power and time
      are the key factors affecting carbazole degradation in this system.

PMID- 22609389
TI  - Electroreduction of hexavalent chromium using a polypyrrole-modified electrode
      under potentiostatic and potentiodynamic conditions.
AB  - Polypyrrole (ppy)-modified electrode was used for electroreduction of Cr(VI) and
      showed favorable advantage with extremely higher removal percentage and current
      efficiency over stainless steel (SS) electrode. In potentiostatic (PS) process
      and in stagnant solution, ppy electrode achieved a Cr(VI) removal efficiency of
      16% and a current efficiency of 23% compared to 0 for SS electrode at a potential
      of -0.8V. In potentiodynamic (PD) process and in stagnant solutions, ppy
      electrode exhibited a Cr(VI) removal efficiency of 56% at a potential range from 
      0.8 to 0.8V whereas SS electrode presented none at the same conditions. Solution
      stirring promoted mass transportation and dramatically improved Cr(VI) removal
      efficiency, achieving 92% (ppy electrode) and 18% (SS electrode) in PS process
      and 100% (ppy electrode) and 36% (SS electrode) in PD process at 100rpm. ppy
      electrode exhibited an efficient Cr(VI) reduction at a wide potential range from 
      0.8 to 0.8V than the potential ranges of -0.8 to 0V and 0-0.8V. While ppy
      stability under PD condition of -0.8 to 0.8V was not as satisfactory as PS
      condition at -0.8V, but better than PS condition at 0.8V. These results
      demonstrate that ppy-modified electrode in PD process may be a promising
      alternative for Cr(VI) electroreduction.

PMID- 22609390
TI  - Sorption of tetracycline on organo-montmorillonites.
AB  - Tetracycline (TC) is a veterinary antibiotic that is frequently detected as
      pollutant in the environment. Powerful adsorbents are required for removing TC.
      The present paper compares the TC adsorption capacity of Na-montmorillonite (Na
      mont) with six organo-montmorillonites (organo-monts). Three quaternary ammonium
      cations (QACs) with different alkyl-chain lengths were used as modifiers. Powder
      X-ray diffraction indicated that the d(001) values of organo-monts increased with
      increasing the QACs loading and alkyl-chain length. The CECs of the organo-monts
      were substantially lower than that of Na-mont and decreased with QACs chain
      length and increased loading. The modeling of the adsorption kinetics revealed
      that the processes of TC adsorption on the tested samples could be well fitted by
      the pseudo-second-order equation. The maximum adsorption capacities of TC on the
      organo-monts (1000-2000mmol/kg) were considerably higher than that on Na-mont
      (769mmol/kg). Both the Langmuir and Freundlich model could fit the adsorption
      isotherms. The TC adsorption to the organo-monts increase significantly with
      decreasing the pH below 5.5 because of the electrostatic interaction, and a high
      QACs loading performed better than a low loading at around pH 3.

PMID- 22609391
TI  - Road-deposited sediments in an urban environment: A first look at sequentially
      extracted element loads in grain size fractions.
AB  - Sediments stored in urban drainage basins are important environmental archives
      for assessing contamination. Few studies have examined the geochemical
      fractionation of metals in individual grain size classes of solid environmental
      media. This is the first study of road sediments to quantify the mass loading of
      Al, Cu, Pb, and Zn in individual grain size classes (<63MUm to 1000-2000MUm) and
      partition contributions amongst four sequentially extracted fractions (acid
      extractable, reducible, oxidizable, and residual). The optimized BCR sequential
      extraction procedure was applied to road sediments from Palolo Valley, Oahu,
      Hawaii. Road sediments from this non-industrialized drainage basin exhibited
      significant enrichment in Cu, Pb, and Zn. Metal mass loading results indicate
      that the <63MUm grain size class dominated almost all fraction loads for a given
      element. The residual fraction dominated the Al loading for this geogenic
      element. The reducible fraction, associated with Fe and Mn oxides, was the most
      important component for Cu, Pb, and Zn loading. These results have direct
      implications for environmental planners charged with reducing sediment-associated
      contaminant transport in urbanized drainage basins.

PMID- 22609392
TI  - Effect of effluent organic matter on the adsorption of perfluorinated compounds
      onto activated carbon.
AB  - Effect of effluent organic matter (EfOM) on the adsorption of perfluorooctane
      sulfonate (PFOS) and perfluorooctanoate (PFOA) onto powdered activated carbon
      (PAC) was quantitatively investigated at environmentally relevant concentration
      levels. The adsorption of both perfluorinated compounds (PFCs) onto PAC followed
      pseudo-second order kinetics and fitted the Freundlich model well under the given
      conditions. Intraparticle diffusion was found to be the rate-controlling step in
      the PFC adsorption process onto PAC in the absence and presence of EfOM. The
      presence of EfOM, either in PFC-EfOM simultaneous adsorption onto fresh PAC or in
      PFC adsorption onto EfOM-preloaded PAC, significantly reduced the adsorption
      capacities and sorption rates of PFCs. The pH of zero point of charge was found
      to be 7.5 for fresh PAC and 4.2 for EfOM-preloaded PAC, suggesting that the
      adsorbed EfOM imparted a negative charge on PAC surface. The effect of molecular
      weight distribution of EfOM on the adsorption of PFCs was investigated with two
      EfOM fractions obtained by ultrafiltration. The low-molecular-weight compounds
      (<1kDa) were found to be the major contributors to the significant reduction in
      PFC adsorption capacity, while large-molecular-weight compounds (>30kDa) had much
      less effect on PFC adsorption capacity.

PMID- 22609393
TI  - Novel polysiloxane resin functionalized with dicyclohexano-18-crown-6 (DCH18C6):
      Synthesis, characterization and extraction of Sr(II) in high acidity HNO3 medium.
AB  - A novel kind of polysiloxane resin functionalized with dicyclohexano-18-crown-6
      (DCH18C6) was synthesized through a post-modification approach. The DCH18C6
      moieties bearing amino groups were firstly prepared, followed by covalent
      grafting to a silica precursor P-(CH(2))(3)-Cl (Where P represents a 3
      dimentional polymerized silica matrix) based on nucleophilic substitution
      reaction. (29)Si and (13)C solid-state NMR, FT-IR, XPS, TGA, ESEM and elemental
      analysis were employed to systematically characterize the structure, thermal
      property and surface morphology of the functionalized resin. The results
      indicated that the DCH18C6 ligands were successfully bonded to the polysiloxane
      resin with a satisfactory grafting degree (33.6wt.%). Due to the robust
      organosilica framework and the covalent immobilization of the ligands, the
      functionalized resin had excellent thermal stability and acid resistance. Batch
      experiments showed that the resin could effectively separate Sr(II) in high
      acidity mediums. The distribution coefficient (K(d)) of 43.6cm(3)/g could be
      achieved in 5.0mol/L HNO(3) solution. The influences of contact time and acidity
      of HNO(3) on the resin's extraction performance were examined. The reusability
      and the selectivity to Sr(II) over interference ions were investigated. The
      DCH18C6-functionalized resin might be potentially applied for the radiostrontium
      removal in the high level liquid waste (HLLW).

PMID- 22609394
TI  - Total oxidation of propane on Pt/WOx/Al2O3 catalysts by formation of metastable
      Ptdelta+ species interacted with WOx clusters.
AB  - A series of Pt/Al(2)O(3) catalysts with various tungsten oxide loadings were
      prepared by a stepwise wet impregnation method. The catalysts were characterized
      by X-ray diffraction, nitrogen physisorption, Raman, UV-vis diffuse reflectance,
      transmission electron microscopy and infrared spectroscopy of adsorbed probe
      molecules (CO, NH(3) or C(3)H(8)). The propane oxidation activity of Pt/Al(2)O(3)
      catalyst is significantly improved by the addition of tungsten oxide. The
      tungsten oxide overlayer is presented as monomeric/polymeric WO(x) clusters and
      WO(3) crystals depending on the loading amount. The most active catalyst occurs
      at an intermediate surface tungsten density corresponding to the maximum of
      polytungstate species. The electronic interactions between Pt and WO(x) clusters
      lead to the generation of more reducible Pt(delta+) species which are suggested
      to be active sites for propane oxidation. Basically, a simple model is proposed
      involving the initial CH bond activation at the platinum-tungsten oxide
      interface.

PMID- 22609395
TI  - Synthesis of Fe nanoparticles@graphene composites for environmental applications.
AB  - Fe nanoparticles@graphene composites (FGC) are successfully synthesized by using
      graphene oxide (GO) as a supporting matrix. GO is first treated with Fe(3+) to
      form Fe(3+)@GO complexes. Then, by adding NaBH(4) solution, Fe(3+) and GO are
      simultaneously reduced in situ to Fe and graphene respectively, forming FGC
      hybrid composites. The structures, properties and applications of the hybrids
      thus obtained are investigated by X-ray diffraction, Raman spectroscopy, Fourier
      transformed infrared spectroscopy, X-ray photoelectron spectroscopy, transmission
      electron microscopy, energy-dispersive X-ray spectroscopy, thermogravimetric
      analysis and magnetization measurements. The hybrids are also evaluated for
      decolorization of methyl blue solution, a model dye in wastewater of dyeing
      industry. Compared with bare Fe particles, the high removal capacities of FGC are
      due to the increased adsorption sites in the hybrids, which are achieved by
      inhibiting the particle aggregation and reducing the size of Fe nanoparticles.

PMID- 22609396
TI  - Bi2MoO6 microtubes: Controlled fabrication by using electrospun polyacrylonitrile
      microfibers as template and their enhanced visible light photocatalytic activity.
AB  - In this paper, Bi(2)MoO(6) microtubes (BMO-MTs) were obtained by a two-step
      fabrication route. By using the electrospun polyacrylonitrile (PAN) microfibers
      as structure-directing hard template and through ethylene glycol solvothermal
      method, polyacrylonitrile/Bi(2)MoO(6) (PAN/BMO) hybrid microfibers with core
      shell structures were prepared. Through heat treatment of the as-prepared PAN/BMO
      to remove the PAN core, Bi(2)MoO(6) with tubes-structured were obtained. The
      thickness of BMO-MTs was controlled by changing the Bi(2)MoO(6) loading
      percentage of PAN/BMO which could be obtained through ethylene glycol
      solvothermal process with precursor different concentration for the preparation
      of Bi(2)MoO(6). And, the crystal structure and morphology of BMO-MTs strongly
      depended on the calcination temperature when heat-treating the as-prepared
      PAN/BMO. Photocatalytic tests show that the BMO-MTs possess a much higher
      degradation rate of Rhodamine B (RB) than that of Bi(2)MoO(6) prepared by solid
      state reaction and conventional P25. The improved photocatalytic performance
      could be ascribed to the hollow multi channelled structure and large surface
      area. The BMO-MTs could be reclaimed easily by sedimentation from the
      photocatalytic reaction solution due to the large length to diameter ratio of one
      dimensional tubes structures. Moreover, such simple and versatile strategy can
      provide a general way to fabricate other tubes structures of Bi(III)-containing
      oxides, such as Bi(2)WO(6) and BiVO(4) microtubes.

PMID- 22609397
TI  - The relationship between body mass index and unhealthy weight control behaviors
      among adolescents: the role of family and peer social support.
AB  - Adolescents classified as overweight or obese are more likely to use unhealthy
      weight control behaviors such as skipping meals or fasting than their healthy
      weight peers. Adolescents with low perceived social support may be at particular
      risk. Therefore, the purpose of the present study was to investigate the
      association between adolescent overweight and obesity, indices of perceived peer
      and family social support, and their interaction in the use of unhealthy weight
      control behaviors among adolescents. The present study used data from the 2001
      2002 Health Behavior in School-Aged Children collaborative survey. Participants
      included 4598 adolescent girls and boys in the ninth and tenth grades. Results of
      binary logistic regression analyses showed that obese boys and girls were more
      likely to use unhealthy weight control behaviors than their healthy weight peers.
      Boys and girls who endorsed difficult communication with their parents, low
      levels of parent school support, or frequent bullying were more likely to engage
      in unhealthy weight control behaviors than relevant comparison groups. Among
      girls, poor classmate relationships were associated with increased use of
      unhealthy weight control behaviors whereas fewer friendships were associated with
      decreased use. Results suggest that adolescents are at high risk for use of
      unhealthy weight control behaviors and would benefit from interventions to
      increase knowledge and social support for achieving and maintaining a healthy
      weight.

PMID- 22609398
TI  - Chromatin repositioning activity and transcription machinery are both recruited
      by Ace1p in yeast CUP1 activation.
AB  - The relationship among transcriptional activators, nucleosome repositioning
      activity and transcription machinery at the yeast CUP1 gene was addressed. CUP1
      encodes a cysteine-rich, copper-binding metallothionein that protects cells
      against copper toxicity through its ability to sequester copper. The induction of
      CUP1 requires the presence of Ace1p and the binding of Ace1p at the CUP1 promoter
      during activation provides evidence that Ace1p is directly involved in CUP1
      induction. Furthermore, transcriptional activation of CUP1 resulted in nucleosome
      repositioning at the CUP1 promoter and sequences further downstream in the coding
      region, suggesting a gene-wide chromatin remodeling activity. Such remodeling
      activity depends on the presence of transcription activator Ace1p. The
      recruitment of RNA polymerase II also requires the presence of Ace1p. Therefore,
      these observations provide insight into the molecular mechanism of CUP1
      activation.

PMID- 22609399
TI  - Jab1 interacts with brain-specific kinase 2 (BRSK2) and promotes its degradation
      in the ubiquitin-proteasome pathway.
AB  - Brain-specific kinase 2 (BRSK2) was classified as an AMP-activated protein kinase
      (AMPK)-related kinase and one of the substrates of LKB1. Studies on homologs of
      BRSK2 in mice, SADA and SADB, implied that it might be involved in the regulation
      of cell polarity and cell cycle. However, physiological functions and molecular
      regulatory mechanisms of BRSK2 are incompletely understood. In this study, we
      isolated a novel BRSK2-interacting protein, c-Jun activation domain-binding
      protein-1 (Jab1), which was reported to mediate degradation of multiple proteins
      and positively regulate cell cycle progression. GST pull-down and
      immunoprecipitation assays revealed the direct interaction between BRSK2 and Jab1
      in vitro and in vivo, respectively. The co-localization between Jab1 and BRSK2 in
      the perinuclear region was observed. Intriguingly, Jab1 promoted the
      ubiquitination and proteasome-dependent degradation of BRSK2. Silencing of
      endogenous Jab1 increased the cellular BRSK2 protein level. Consistent with this,
      BRSK2-mediated cell cycle arrest at the G2/M phase in mammalian cells was
      reversed by exogenous Jab1. Taken together, our findings provide a novel
      regulatory mechanism of BRSK2 through direct interaction with Jab1.

PMID- 22609400
TI  - miR-21 modulates tumor outgrowth induced by human adipose tissue-derived
      mesenchymal stem cells in vivo.
AB  - Mesenchymal stem cells (MSCs) have generated a great deal of interest in clinical
      situations, due principally to their potential use in regenerative medicine and
      tissue engineering applications. However, the therapeutic application of MSCs
      remains limited, unless the favorable effects of MSCs on tumor growth in vivo,
      and the long-term safety of the clinical applications of MSCs, can be more
      thoroughly understood. In this study, we determined whether microRNAs can
      modulate MSC-induced tumor outgrowth in BALB/c nude mice. Overexpression of miR
      21 in human adipose-derived stem cells (hADSCs) inhibited hADSC-induced tumor
      growth, and inhibition of miR-21 increased it. Downregulation of transforming
      growth factor beta receptor II (TGFBR2), but not of signal transducer and
      activator of transcription 3, in hADSCs showed effects similar to those of miR-21
      overexpression. Downregulation of TGFBR2 and overexpression of miR21 decreased
      tumor vascularity. Inhibition of miR-21 and the addition of TGF-beta increased
      the levels of vascular endothelial growth factor and interleukin-6 in hADSCs.
      Transplantation of miR-21 inhibitor-transfected hADSCs increased blood flow
      recovery in a hind limb ischemia model of nude mice, compared with
      transplantation of control oligo-transfected cells. These findings indicate that
      MSCs might favor tumor growth in vivo. Thus, it is necessary to study the long
      term safety of this technique before MSCs can be used as therapeutic tools in
      regenerative medicine and tissue engineering.

PMID- 22609401
TI  - Molecular basis for the interplay of apoptosis and proliferation mediated by Bcl
      xL:Bim interactions in pancreatic cancer cells.
AB  - A major mechanism through which cancer cells avoid apoptosis is by promoting the
      association of anti-apoptotic members of the pro-survival Bcl-2 protein family
      (like Bcl-2 and Bcl-xL) with BH(3) domain-only proteins (like Bim and Bid).
      Apoptosis and cell proliferation have been shown to be linked for many cancers
      but the molecular basis for this link is far from understood. We have identified
      the Bcl-xL:Bim protein-protein interface as a direct regulator of proliferation
      and apoptosis in pancreatic cancer cells. We were able to predict and
      subsequently verify experimentally the effect of various Bcl-xL single-point
      mutants (at the position A142) on binding to Bim by structural analysis and
      computational modeling of the inter-residue interactions at the Bcl-xL:Bim
      protein-protein interface. The mutants A142N, A142Q, and A142Y decreased binding
      of Bim to Bcl-xL and A142S increased this binding. The Bcl-xL mutants, with
      decreased affinity for Bim, caused an increase in apoptosis and a corresponding
      decrease in cell proliferation. However, we could prevent these effects by
      introducing a small interfering RNA (siRNA) targeted at Bim. These results show a
      novel role played by the Bcl-xL:Bim interaction in regulating proliferation of
      pancreatic cancer cells at the expense of apoptosis. This study presents a
      physiologically relevant model of the Bcl-xL:Bim interface that can be used for
      rational therapeutic design for the inhibition of proliferation and cancer cell
      resistance to apoptosis.

PMID- 22609402
TI  - Cyclophilin A inhibits rotavirus replication by facilitating host IFN-I
      production.
AB  - Rotavirus (RV) infection causes serious dehydrating diarrhoea in infants and
      newborn animals. Our previous study revealed that cyclophilin A (CYPA), a
      peptidyl-prolyl cis-trans isomerase (PPIase), could be temporarily upregulated in
      RV-infected MA104 cells in early stage of infection (unpublished data). To find
      out the possible roles of CYPA in RV infection, we overexpressed and silenced
      CYPA in various cell lines by gene transfection and shRNA. We found that
      transfection of CYPA significantly inhibited RV replication, while silencing the
      expression of CYPA significantly increased RV replication. Accordingly,
      overexpression of CYPA significantly increased IFN-beta production; while
      silencing CYPA significantly reduced IFN-beta production. This effect of CYPA on
      IFN-beta production was independent of its PPIase activity. Moreover, IFN-beta
      secreted by host cells in RV infection had a critical repressive effect on viral
      replication. Finally, we found that inhibiting JNK pathway by SP600125 and JNK
      siRNA abrogated the effect of CYPA on IFN-beta transcription in RV-infected MA104
      cells. Together, our data suggested that CYPA inhibited RV replication by
      facilitating host IFN-beta production, which was independent on the PPIase
      activity of CYPA but dependent on the activation of JNK signaling pathway.

PMID- 22609403
TI  - The 21.5-kDa isoform of myelin basic protein has a non-traditional PY-nuclear
      localization signal.
AB  - The predominant 18.5-kDa classic myelin basic protein (MBP) is mainly responsible
      for compaction of the myelin sheath in the central nervous system, but is
      multifunctional, having numerous interactions with Ca(2+)-calmodulin, actin,
      tubulin, and SH3-domains, and can tether these proteins to a lipid membrane in
      vitro. The full-length 21.5-kDa MBP isoform has an additional 26 residues encoded
      by exon-II of the classic gene, which causes it to be trafficked to the nucleus
      of oligodendrocytes (OLGs). We have performed site-directed mutagenesis of
      selected residues within this segment in red fluorescent protein (RFP)-tagged
      constructs, which were then transfected into the immortalized N19-OLG cell line
      to view protein localization using epifluorescence microscopy. We found that 21.5
      kDa MBP contains two non-traditional PY-nuclear-localization signals, and that
      arginine and lysine residues within these motifs were involved in subcellular
      trafficking of this protein to the nucleus, where it may have functional roles
      during myelinogenesis.

PMID- 22609404
TI  - Role of S100A12 in the pathogenesis of osteoarthritis.
AB  - S100A12 is a member of the S100 protein family, which are intracellular calcium
      binding proteins. Although there are many reports on the involvement of S100A12
      in inflammatory diseases, its presence in osteoarthritic cartilage has not been
      reported. The purpose of this study was to investigate the expression of S100A12
      in human articular cartilage in osteoarthritis (OA) and to evaluate the role of
      S100A12 in human OA chondrocytes. We analyzed S100A12 expression by
      immunohistochemical staining of cartilage samples obtained from OA and non-OA
      patients. In addition, chondrocytes were isolated from knee cartilage of OA
      patients and treated with recombinant human S100A12. Real-time RT-PCR was
      performed to analyze mRNA expression. Protein production of matrix
      metalloproteinase 13 (MMP-13) and vascular endothelial growth factor (VEGF) in
      the culture medium were measured by ELISA. Immunohistochemical analyses revealed
      that S100A12 expression was markedly increased in OA cartilages. Protein
      production and mRNA expression of MMP-13 and VEGF in cultured OA chondrocytes
      were significantly increased by treatment with exogenous S100A12. These increases
      in mRNA expression and protein production were suppressed by administration of
      soluble receptor for advanced glycation end products (RAGE). Both p38 mitogen
      activated protein kinase (MAPK) and nuclear factor-kappaB (NF-kappaB) inhibitors
      also suppressed the increases in mRNA expression and protein production of MMP-13
      and VEGF. We demonstrated marked up-regulation of S100A12 expression in human OA
      cartilages. Exogenous S100A12 increased the production of MMP-13 and VEGF in
      human OA chondrocytes. Our data indicate the possible involvement of S100A12 in
      the development of OA by up-regulating MMP-13 and VEGF via p38 MAPK and NF-kappaB
      pathways.

PMID- 22609405
TI  - Inhibition of cell proliferation and induction of apoptosis by oleanane
      triterpenoid (CDDO-Me) in pancreatic cancer cells is associated with the
      suppression of hTERT gene expression and its telomerase activity.
AB  - Methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) is a
      multifunctional oleanane synthetic triterpenoid with potent anti-inflammatory and
      antitumorigenic properties. The mechanisms of the antisurvival and apoptosis
      inducing activities of CDDO-Me and related derivatives of oleanolic acid have
      been defined; however, to date, no study has been carried out on the effect of
      CDDOs on human telomerase reverse transcriptase (hTERT) gene or telomerase
      activity. Here we report for the first time that inhibition of cell proliferation
      and induction of apoptosis by CDDO-Me in pancreatic cancer cell lines is
      associated with the inhibition of hTERT gene expression, hTERT telomerase
      activity and a number of proteins that regulate hTERT expression and activity.
      Furthermore, abrogation or overexpression of hTERT protein altered the
      susceptibility of tumor cells to CDDO-Me. These findings suggest that telomerase
      (hTERT) is a relevant target of CDDO-Me in pancreatic cancer cells.

PMID- 22609406
TI  - Smooth muscle protein 22 alpha-Cre is expressed in myeloid cells in mice.
AB  - BACKGROUND: Experiments using Cre recombinase to study smooth muscle specific
      functions rely on strict specificity of Cre transgene expression. Therefore,
      accurate determination of Cre activity is critical to the interpretation of
      experiments using smooth muscle specific Cre. METHODS AND RESULTS: Two lines of
      smooth muscle protein 22 alpha-Cre (SM22alpha-Cre) mice were bred to floxed mice
      in order to define Cre transgene expression. Southern blotting demonstrated that
      SM22alpha-Cre was expressed not only in tissues abundant of smooth muscle, but
      also in spleen, which consists largely of immune cells including myeloid and
      lymphoid cells. PCR detected SM22alpha-Cre expression in peripheral blood and
      peritoneal macrophages. Analysis of SM22alpha-Cre mice crossed with a
      recombination detector GFP mouse revealed GFP expression, and hence
      recombination, in circulating neutrophils and monocytes by flow cytometry.
      CONCLUSIONS: SM22alpha-Cre mediates recombination not only in smooth muscle
      cells, but also in myeloid cells including neutrophils, monocytes, and
      macrophages. Given the known contributions of myeloid cells to cardiovascular
      phenotypes, caution should be taken when interpreting data using SM22alpha-Cre
      mice to investigate smooth muscle specific functions. Strategies such as bone
      marrow transplantation may be necessary when SM22alpha-Cre is used to
      differentiate the contribution of smooth muscle cells versus myeloid cells to
      observed phenotypes.

PMID- 22609407
TI  - CK2 regulates ATF4 and CHOP transcription within the cellular stress response
      signalling pathway.
AB  - Protein kinase CK2 is an ubiquitously expressed serine/threonine kinase. The
      protein levels along with CK2 activity are highly elevated in tumour cells where
      it protects cells from apoptosis. Accordingly, inhibition of CK2 is known to
      induce programmed cell death, making it a promising target for cancer therapy.
      Analysis of the different behaviour of hormone sensitive LNCaP cells and hormone
      refractory PC-3 cells after CK2 inhibition revealed CHOP ((C/EBP)-homologous
      protein) induction and therefore probably ER stress as crucial for apoptosis in
      the LNCaP cells. In the present study we investigated which promoter element of
      the CHOP promoter is responsible for its induction. ER stress can be generated by
      the accumulation of unfolded proteins, by depletion of amino acids or by
      oxidative stress. ER stress induces specific signalling pathways. In order to
      analyse which pathway might be activated by CK2 inhibition we started to analyse
      the activation of the different CHOP promoter elements. By using mutated reporter
      constructs of the CHOP promoter, it turned out that the amino acid response
      element (AARE) is the most prominent element for CHOP induction after CK2
      inhibition. The ER stress element, however, proves to be less crucial, and along
      with the AP-1 binding site, they do not seem to play any role. Further we found
      an up-regulation of the transcription factor ATF4 after CK2 inhibition. ATF4 is
      involved in ER stress signalling through the AARE, which further supports our
      finding that CK2 inhibition provokes an amino acid induced response pathway.

PMID- 22609408
TI  - Improved biological phosphorus removal performance driven by the aerobic/extended
      idle regime with propionate as the sole carbon source.
AB  - Our previous studies proved that biological phosphorus removal (BPR) could be
      achieved in an aerobic/extended-idle (AEI) process employing two typical
      substrates of glucose and acetate as the carbon sources. This paper further
      evaluated the feasibility of another important substrate, propionate, serving as
      the carbon source for BPR in the AEI process, and compared the BPR performance
      between the AEI and anaerobic/oxic (A/O) processes. Two sequencing batch reactors
      (SBRs) were operated, respectively, as the AEI and A/O regimes for BPR using
      propionate as the sole substrate. The results showed that the AEI-reactor removed
      2.98 +/- 0.04-4.06 +/- 0.06 mg of phosphorus per g of total suspended solids
      during the course of the steady operational trial, and the phosphorus content of
      the dried sludge was reached 8.0 +/- 0.4% after 56-day operation, demonstrating
      the good performance of phosphorus removal. Then, the efficiencies of BPR and the
      transformations of the intracellular storages were compared between two SBRs. It
      was observed that the phosphorus removal efficiency was maintained around 95% in
      the AEI-reactor, and about 83% in the A/O-reactor, although the latter showed
      much greater transformations of both polyhydroxyalkanoates and glycogen. The
      facts clearly showed that BPR could be enhanced by the AEI regime using
      propionate as the carbon source. Finally, the mechanisms for the propionate fed
      AEI-reactor improving BPR were investigated. It was found that the sludge
      cultured by the AEI regime had more polyphosphate containing cells than that by
      the A/O regime. Further investigation revealed that the residual nitrate
      generated in the last aerobic period was readily deteriorated BPR in the A/O-SBR,
      but a slight deterioration was observed in the AEI-SBR. Moreover, the lower
      glycogen transformation measured in the AEI-SBR indicated that the biomass
      cultured by the AEI regime contained less glycogen accumulating organisms
      activities than that by the A/O regime.

PMID- 22609409
TI  - Detection of Helicosporidium spp. in metagenomic DNA.
AB  - Distinct isolates of the invertebrate pathogenic alga Helicosporidium sp.,
      collected from different insect hosts and different geographic locations, were
      processed to sequence the 18S rDNA and beta-tubulin genes. The sequences were
      analyzed to assess genetic variation within the genus Helicosporidium and to
      design Helicosporidium-specific 18S rDNA primers. The specificity of these
      primers was demonstrated by testing not only on the Helicosporidium sp. isolates,
      but also on two trebouxiophyte algae known to be close Helicosporidium relatives,
      Prototheca wickerhamii and Prototheca zopfii. The genus-specific primers were
      used to develop a culture-independent assay aimed at detecting the presence of
      Helicosporidium spp. in environmental waters. The assay was based on the PCR
      amplification of 18SrDNA gene fragments from metagenomic DNA preparations, and it
      resulted in the amplification of detectable products for all sampled sites.
      Phylogenetic analyses that included the environmental sequences demonstrated that
      all amplification products clustered in a strongly supported, monophyletic
      Helicosporidium clade, thereby validating the metagenomic approach and the
      taxonomic origin of the produced environmental sequences. In addition, the
      phylogenetic analyses established that Helicosporidium spp. isolated from
      coleopteran hosts are more closely related to each other than they are to the
      isolate collected from a dipteran host. Finally, the phylogenetic trees depicted
      intergeneric relationships that supported a Helicosporidium-Prototheca cluster
      but did not support a Helicosporidium-Coccomyxa grouping, suggesting that
      pathogenicity to invertebrates evolved at least twice independently within the
      trebouxiophyte green algae.

PMID- 22609411
TI  - Severe ocular injury after button battery exposure.
AB  - BACKGROUND: Button batteries can cause local tissue necrosis within 2h of
      exposure due to hydrolysis of tissue fluid and generation of hydroxide ions.
      Tissue damage resulting from battery exposure has been associated with acute and
      chronic complications via several routes, however, previous experience with
      ocular battery exposures is predominantly limited to batteries that have exploded
      or penetrated the eye. OBJECTIVES: A case is presented of an intact battery
      causing significant damage after ocular exposure without penetrating the eye.
      CASE REPORT: An 18-year-old woman presented to the Emergency Department after a
      toy balloon propelled a button battery into the patient's eye. The battery did
      not penetrate the orbit and was intact upon removal from the inferior fornix in
      the operating room 4h later. The patient had severe conjunctival ulceration,
      subconjunctival hemorrhage, vitreous opacification, and a partially dilated
      pupil, with the greatest area of injury adjacent to the negative pole of the
      battery. The eye was extensively irrigated and the patient was treated with
      topical antibiotics, steroids, and a daily rodding procedure to prevent
      conjunctival adhesions. The eye ultimately healed over the subsequent 6 months,
      with normal visual acuity on follow-up. CONCLUSION: Prolonged ocular exposure to
      an intact battery can cause significant tissue necrosis, which may threaten
      sight. Early removal is critical to prevent significant ocular damage and visual
      compromise.

PMID- 22609410
TI  - Regulation of the surface expression of alpha4beta2delta GABAA receptors by high
      efficacy states.
AB  - alpha4betadelta GABA(A) receptors (GABARs) have low CNS expression, but their
      expression is increased by 48h exposure to the neurosteroid THP (3alpha-OH
      5alpha[beta]-pregnan-20-one). THP also increases the efficacy of delta-containing
      GABARs acutely, where GABA is a partial agonist. Thus, we examined effects of THP
      (100 nM) and full GABA agonists at alpha4beta2delta (gaboxadol, 10 MUM, and beta
      alanine, 10 MUM-1mM), on surface expression of alpha4beta2delta. To this end, we
      used an alpha4 construct tagged with a 3XFLAG (F) epitope or measured expression
      of native alpha4 and delta. HEK-293 cells or cultured hippocampal neurons were
      transfected with alpha4Fbeta2delta and treated 24h later with GABA agonists, THP,
      GABA plus THP or vehicle (0.01% DMSO) for 0.5 h-48 h. Immunocytochemistry was
      performed under both non-permeabilized and permeabilized conditions to detect
      surface and intracellular labeling, respectively, using confocal microscopy. The
      high efficacy agonists and GABA (1 or 10 MUM) plus THP increased alpha4beta2delta
      surface expression up to 3-fold after 48h, an effect first seen by 0.5h. This
      effect was not dependent upon the polarity of GABAergic current, although
      expression was increased by KCC2. Intracellular labeling was decreased while
      functional expression was confirmed by whole cell patch clamp recordings of
      responses to GABA agonists. GABA plus THP treatment did not alter the rate of
      receptor removal from the surface membrane, suggesting that THP-induced
      alpha4beta2delta expression is likely via receptor insertion. Surface expression
      of alpha4beta2delta was decreased by rottlerin (10 MUM), suggesting a role for
      PKC-delta. These results suggest that trafficking of alpha4beta2delta GABARs is
      regulated by high efficacy states.

PMID- 22609412
TI  - A case of imported severe plasmodium falciparum malaria in the emergency
      department and the current role of exchange transfusion treatment.
AB  - BACKGROUND: The role of exchange transfusion in the management of severe malaria
      is not well documented in Emergency Medicine literature. OBJECTIVES: The goal of
      this article is to review the importance of considering malaria in the
      differential diagnosis of the febrile returned traveler and to discuss the role
      of exchange transfusion in the management of severe Plasmodium falciparum
      malaria. CASE REPORT: A 59-year-old woman presented to the Emergency Department
      (ED) with severe P. falciparum malaria. Her physical examination was remarkable
      for scleral icterus, dry mucous membranes, and tachycardia. Her complete blood
      count revealed a white blood cell count of 6.9 k/uL, with 71% segmented
      neutrophils, 19% bands, a hemoglobin level of 11.9 g/dL, hematocrit of 37.2%, and
      a platelet count of 9 k/uL. Hepatorenal impairment was present and malaria
      parasites with ring form were seen on malaria prep in 18% of red blood cells. The
      patient was treated with fluids, platelets, quinidine gluconate, doxycycline, and
      exchange transfusion with significant improvement in the patient's clinical
      condition. CONCLUSIONS: The high level of parasitemia presenting with acute
      kidney injury, hyperbilirubinemia, and thrombocytopenia supported the use of
      exchange transfusion as adjunct therapy. Exchange transfusion was a reasonable
      consideration in this case and was well tolerated by our patient. Institutions
      that are equipped with apheresis units should evaluate each case individually in
      concert with Centers for Disease Control experts and local consultants and weigh
      the risks and benefits of the use of exchange transfusion as an adjunct in the
      treatment of severe P. falciparum malaria.

PMID- 22609413
TI  - Mycobacterium bovis BCG vaccine induces non-specific immune responses in Japanese
      flounder against Nocardia seriolae.
AB  - Nocardiosis caused by Nocardia seriolae has been causing severe loss of fish
      production, so that an effective vaccine is urgently needed. Mycobacterium bovis
      BCG (BCG) is a live attenuated vaccine for tuberculosis, which is effective
      against various infectious diseases including nocardiosis in mammals. In this
      study, the protective efficacy of BCG against N. seriolae was evaluated in
      Japanese flounder Paralichthys olivaceus and antigen-specific immune responses
      induced in BCG vaccinated fish were investigated. Cumulative mortality of BCG
      vaccinated fish was 21.4% whereas that of PBS-injected fish was 56.7% in N.
      seriolae challenge. However, gene expression level of IFN-gamma was only slightly
      up-regulated in BCG-vaccinated fish after injection of N. seriolae antigen. In
      order to reveal non-specific immune responses induced by BCG vaccination,
      transcriptome of the kidney after BCG vaccination was investigated using oligo
      DNA microarray. Gene expression levels of antimicrobial peptides such as C-type
      and G-type lysozyme were significantly up-regulated after BCG vaccination.
      Consistently, BCG vaccination appeared to increase the bacteriolysis activity of
      the serum against Micrococcus luteus and N. seriolae. These results suggest that
      BCG-vaccinated Japanese flounder fight N. seriolae infection mainly by non
      specific immune responses such as by the production of bacteriolytic lysozymes.

PMID- 22609414
TI  - [Effects on children's cognitive development of chronic exposure to screens].
AB  - During the last few years, the time spent in front of various screens, including
      TV sets, video games, smartphones and computers, has dramatically increased.
      Numerous studies show, with a remarkable consistency, that this trend has a
      strong negative influence on the cognitive development of children and teenagers.
      The affected fields include, in particular, scholastic achievement, language,
      attention, sleep and aggression. We believe that this often disregarded - not to
      say denied - problem should now be considered a major public health issue.
      Primary care physicians should inform parents and children about this issue to
      support efficient prevention.

PMID- 22609415
TI  - Effects of Trx2p and Sec23p expression on stable production of hepatitis B
      surface antigen S domain in recombinant Saccharomyces cerevisiae.
AB  - The S domain of hepatitis B virus surface antigen (sHBsAg) is the primary
      component for vaccine development against virus infection. For stable expression
      of sHBsAg in recombinant Saccharomyces cerevisiae, new accessory genes necessary
      for foreign protein expression were screened by DNA microarray. Among 600 genes
      of interest, genes coding for an activating protein of ATPase in Hsp90 (Aha1p),
      S. cerevisiae DnaJ (Scj1p), thioredoxin 2 (Trx2p) and a GTPase-activator specific
      for Sar1 (Sec23p) as well as Pdi1p were selected in transcriptome analysis, which
      are known to facilitate disulfide bond formation or induce protein transport in
      the secretion pathway. Individual and combinatorial expression of SEC23, TRX2 and
      PDI1 increased total sHBsAg concentration by 1.9-6.5-fold, relative to the
      control strain expressing sHBsAg only. Additionally, moderate expression of Kex2p
      protease able to cut off the signal peptide enhanced the portion of the authentic
      sHBsAg to total sHBsAg. Fed-batch fermentation of the S. cerevisiae 2805 strain
      coexpressing the sHBsAg, SEC23, PDI1 and KEX2 genes resulted in 70.6mg/L final
      sHBsAg concentration which was 5.6 times higher than that of the control.
      Transmission electron microscopic analysis of the yeast cells elucidated the
      effects of the accessory gene coexpression on the intracellular localization of
      sHBsAg. Like PDI1, coexpression of both SEC23 and/or TRX2 newly isolated in this
      study is expected to improve the target protein expression in S. cerevisiae.

PMID- 22609416
TI  - Non-canonical residues of the marginally stable monomeric ubiquitin conjugase
      from goldfish are involved in binding to the C terminus of Ring 1B.
AB  - E2 ubiquitin conjugases are ~20kDa enzymes involved in ubiquitination processes
      in eukaryotes. The E2s are responsible for the transference of ubiquitin (Ub) to
      E3 enzymes, which finally transfer Ub to diverse target proteins, labelling them
      for degradation, localization and regulation. Although their functions are
      relatively well-characterized, their conformational stabilities are poorly known.
      In this work, we have used, as a model for our biophysical and binding studies,
      the E2-C from Carassius auratus (goldfish), a homologue of the human ubiquitin
      conjugase UbcH10. E2-C(ca) was a monomeric protein with an elongated shape;
      moreover, the protein was only marginally stable within a narrow pH range (from
      6.0 to 8.0). We also explored the binding of E2-C(ca) towards non-canonical E3
      ligases. Binding of E2-C(ca) to the C terminus of murine Ring 1B (C-Ring1B),
      which does not contain the RING finger of the whole Ring1B, occurred with an
      affinity of ~400nM, as shown by fluorescence and ITC. Furthermore, binding of E2
      C(ca) to C-Ring1B did not occur at its canonical E2-loops, since residues M43 and
      F53, far away from those loops, were involved in binding. Thus, the C-Ring1B
      interacting region of E2-C(ca) comprises the first beta-strand and nearby
      residues.

PMID- 22609417
TI  - Size, orientation and organization of oligomers that nucleate amyloid fibrils:
      clues from MD simulations of pre-formed aggregates.
AB  - All-atom MD simulations of pre-formed aggregates of GNNQQNY with variable size (5
      to 16 peptides), orientation (parallel or anti-parallel), organization (single or
      double sheet, with or without twist), charge status of termini and temperature
      (300 and 330K) have been performed for 50ns each (68 simulations; total
      time=3.4MUs). Double-layer systems are stable irrespective of whether the
      peptides within the sheet are oriented parallel or anti-parallel. The lifetime of
      single sheet systems is determined by the protonation status, nature of
      association of peptides and the size of the aggregates. For example, single sheet
      8-mers are stable with parallel arrangement and neutral termini, or with anti
      parallel arrangement and charged termini. This suggests that the residues
      flanking the amyloidogenic sequence also play an important role in determining
      the organization of peptides in an aggregate. Twist of the cross-beta sheets is
      found to be intrinsic to the aggregates. Main chain H-bonds are key determinants
      of stability and loss of these H-bonds is followed by disorder and/or
      dissociation of the peptide despite the presence of side chain hydrogen bonds.
      Aggregates are inherently asymmetric along the fiber axis and dissociation from
      the C-edge is observed more often. An aggregate can disintegrate into smaller
      sized oligomers or the edge peptides can dissociate sequentially. A variety of
      dissociation and disintegration events are observed pointing to the existence of
      multiple pathways for association during nucleation. It appears that a
      heterogeneous mixture of oligomers of different sizes exist prior to the
      formation of the critical nucleus.

PMID- 22609418
TI  - Insecticidal activity of wheat Hessian fly responsive proteins HFR-1 and HFR-3
      towards a non-target wheat pest, cereal aphid (Sitobion avenae F.).
AB  - The interaction between Hessian fly (Mayetiola destructor) and wheat (Triticum
      aestivum) involves a gene-for-gene resistance mechanism. The incompatible
      interaction leading to resistance involves up-regulation of several Hfr (Hessian
      fly responsive) genes encoding proteins with potential insecticidal activity. The
      encoded proteins HFR-1, HFR-2 and HFR-3 all possess lectin-like domains. HFR-1
      and HFR-3 were produced as recombinant proteins using Escherichia coli and Pichia
      pastoris, respectively as expression hosts. Purified recombinant proteins were
      assayed for insecticidal effects towards cereal aphid (Sitobion avenae), an
      insect to which wheat shows only tolerance. Both HFR-1 and HFR-3 were found to be
      insecticidal towards S. avenae when fed in artificial diet. Although HFR-3 has
      sequence similarity and similar chitin-binding activity to wheat germ agglutinin
      (WGA), the latter protein was almost non-toxic to S. avenae. HFR-3 binds strongly
      to aphid midguts after ingestion, whereas WGA binds but does not persist over a
      feed-chase period. Quantitative PCR showed that Hfr-3 mRNA does not increase in
      level after cereal aphid infestation. The results suggest that the lack of
      effective resistance to cereal aphid in wheat is not due to an absence of genes
      encoding suitable insecticidal proteins, but results from a failure to up
      regulate gene expression in response to aphid attack.

PMID- 22609419
TI  - Polarotaxis in egg-laying yellow fever mosquitoes Aedes (Stegomyia) aegypti is
      masked due to infochemicals.
AB  - Aquatic and water-associated insects need to locate suitable bodies of water to
      lay their eggs in and allow their aquatic larvae to develop. More than 300
      species are known to solve this task by positive polarotaxis, relying primarily
      on the horizontally polarized light reflected from the water surface. The yellow
      fever mosquito Aedes (Stegomyia) aegypti has been thought to be an exception,
      locating its breeding habitats by chemical cues like odour of conspecifics, their
      eggs, or water vapour. We now demonstrate through dual-choice experiments that
      horizontally polarized light can also attract ovipositing Ae. aegypti females
      when the latter are deprived of chemical cues: water-filled transparent egg-trays
      illuminated by horizontally polarized light from below gained a 94.2% higher
      total number of eggs than trays exposed to unpolarized light, but only when no
      chemical substances capable of functioning as cues were present. Ae. aegypti is
      the first known water-associated insect in which polarotaxis exists, but does not
      play a dominant role in locating water bodies and can be constrained in the
      presence of chemical cues.

PMID- 22609420
TI  - Mass spectral determination of phenylacetonitrile (PAN) levels in body tissues of
      adult desert locust, Schistocerca gregaria.
AB  - Wings and legs of the gregarious desert locust, Schistocerca gregaria have been
      shown to be release sites of phenylacetonitrile (PAN), the major adult male
      produced pheromone. However, there is limited information on the distribution of
      PAN within the locust. Here we show, using gas chromatography-mass spectrometry
      (GC-MS), that PAN occurs in nearly all body parts of both adult males and females
      of the locust in varying amounts. PAN was 20-fold more concentrated in males than
      in females. In females, PAN was concentrated more in the tarsal segments. The
      greatest amounts of PAN were in 2- and 3-week old female and male body parts,
      respectively. No trace of PAN was found in similar ages and sexes of the
      solitarious phase desert locust. Our results show that PAN is distributed in the
      body matrix of both sexes of gregarious phase locusts and suggest that no
      specific tissue is responsible for biosynthesis of the pheromone.

PMID- 22609422
TI  - Targeting nucleic acids into mitochondria: progress and prospects.
AB  - Given the essential functions of these organelles in cell homeostasis, their
      involvement in incurable diseases and their potential in biotechnological
      applications, genetic transformation of mitochondria has been a long pursued goal
      that has only been reached in a couple of unicellular organisms. The challenge
      led scientists to explore a wealth of different strategies for mitochondrial
      delivery of DNA or RNA in living cells. These are the subject of the present
      review. Targeting DNA into the organelles currently shows promise but remarkably
      a number of alternative approaches based on RNA trafficking were also established
      and will bring as well major contributions. 

PMID- 22609421
TI  - Dry season reproductive depression of Anopheles gambiae in the Sahel.
AB  - The African malaria mosquito, Anopheles gambiae, is widespread south of the
      Sahara including in dry savannahs and semi-arid environments where no surface
      water exists for several months a year. Adults of the M form of An. gambiae
      persist through the long dry season, when no surface waters are available, by
      increasing their maximal survival from 4 weeks to 7 months. Dry season diapause
      (aestivation) presumably underlies this extended survival. Diapause in adult
      insects is intrinsically linked to depressed reproduction. To determine if
      reproduction of the Sahelian M form is depressed during the dry season, we
      assessed seasonal changes in oviposition, egg batch size, and egg development, as
      well as insemination rate and blood feeding in wild caught mosquitoes. Results
      from xeric Sahelian and riparian populations were compared. Oviposition response
      in the Sahelian M form dropped from 70% during the wet season to 20% during the
      dry season while the mean egg batch size among those that laid eggs fell from 173
      to 101. Correspondingly, the fraction of females that exhibited gonotrophic
      dissociation increased over the dry season from 5% to 45%, while a similar
      fraction of the population retained developed eggs despite having access to
      water. This depression in reproduction the Sahelian M form was not caused by a
      reduced insemination rate. Seasonal variation in these reproductive parameters of
      the riparian M form population was less extreme and the duration of reproductive
      depression was shorter. Blood feeding responses did not change with the season in
      either population. Depressed reproduction during the dry season in the Sahelian M
      form of An. gambiae provides additional evidence for aestivation and illuminates
      the physiological processes involved. The differences between the Sahelian and
      riparian population suggest an adaptive cline in aestivation phenotypes between
      populations only 130 km apart.

PMID- 22609423
TI  - One year of pomegranate juice intake decreases oxidative stress, inflammation,
      and incidence of infections in hemodialysis patients: a randomized placebo
      controlled trial.
AB  - Increased systemic inflammation and oxidative stress are well established as
      nontraditional key players in the pathogenesis of atherosclerosis and are also
      involved in the innate immunity dysregulation in hemodialysis (HD) patients. The
      study aim was to investigate the effect of 1-year intake of pomegranate juice, an
      antioxidant source, on oxidative stress, inflammation, and long-term clinical
      outcomes. A randomized placebo controlled double-blind trial was designed,
      enrolling 101 chronic HD patients to receive during each dialysis 100 cc of
      pomegranate juice, or matching placebo, three times a week for 1 year. The
      primary endpoints were levels of oxidative stress and inflammation biomarkers.
      Secondary endpoints were hospitalization due to infections and the progression of
      atherosclerotic process based on a composite of variables of the carotid
      arteries: intima media thickness (IMT), number, and structure of plaques.
      Pomegranate juice intake yielded a significant time response reduction in
      polymorphonuclear leukocyte priming, protein oxidation, lipid oxidation, and
      inflammation biomarkers levels. These beneficial effects were abolished 3 months
      postintervention. Pomegranate juice intake resulted in a significantly lower
      incidence rate of the second hospitalization due to infections. Furthermore, 25%
      of the patients in the pomegranate juice group had improvement and only 5%
      progression in the atherosclerotic process, while more than 50% of patients in
      the placebo group showed progression and none showed any improvement. Prolonged
      pomegranate juice intake improves nontraditional CV risk factors, attenuates the
      progression of the atherosclerotic process, strengthens the innate immunity, and
      thus reduces morbidity among HD patients.

PMID- 22609424
TI  - Cardioprotection from oxidative stress in the newborn heart by activation of
      PPARgamma is mediated by catalase.
AB  - Regulation of catalase (CAT) by peroxisome proliferator-activated receptor-gamma
      (PPARgamma) was investigated to determine if PPARgamma activation provides
      cardioprotection from oxidative stress caused by hydrogen peroxide (H(2)O(2)) in
      an age-dependent manner. Left ventricular developed pressure (LVDP) was measured
      in Langendorff perfused newborn or adult rabbit hearts, exposed to 200MUM
      H(2)O(2), with perfusion of rosiglitazone (RGZ) or pioglitazone (PGZ), PPARgamma
      agonists. We found: (1) H(2)O(2) significantly decreased sarcomere shortening in
      newborn ventricular cells but not in adult cells. Lactate dehydrogenase (LDH)
      release occurred earlier in newborn than in adult heart, which may be due, in
      part, to the lower expression of CAT in newborn heart. (2) RGZ increased CAT mRNA
      and protein as well as activity in newborn but not in adult heart. GW9662
      (PPARgamma blocker) eliminated the increased CAT mRNA by RGZ. (3) In newborn
      heart, RGZ and PGZ treatment inhibited release of LDH in response to H(2)O(2)
      compared to H(2)O(2) alone. GW9662 decreased this inhibition. (4) LVDP was
      significantly higher in both RGZ+H(2)O(2) and PGZ+H(2)O(2) groups than in the
      H(2)O(2) group. Block of PPARgamma abolished this effect. In contrast, there was
      no effect of RGZ in adult. (5) The cardioprotective effects of RGZ were abolished
      by inhibition of CAT. In conclusion, PPARgamma activation is cardioprotective to
      H(2)O(2)-induced stress in the newborn heart by upregulation of catalase. These
      data suggest that PPARgamma activation may be an effective therapy for the young
      cardiac patient.

PMID- 22609425
TI  - Development of the dietary fiber functional food and studies on its toxicological
      and physiologic properties.
AB  - Dietary fiber (DF) obtained from wheat bran by microbial fermentation was used as
      a food additive to cookies. The cookies were evaluated sensorally through an
      orthogonal test to gain the optimized production conditions as follows: the
      suitable DF content 8%, leavening agent 1.5%, standing time 5 min, and baking
      time of the cookies is 8 min. A series of toxicological and physiological
      functions of the cookies were studied using KM mice as the experimental animal in
      this paper. No deaths or abnormal behaviors of mice occurred either in acute
      toxicity tests or in short-term feeding tests. Besides, the weight gains, food
      utilization ratios, blood and serum biochemical parameters, organ coefficients
      and the results of organ histopathology tests of all doses groups exhibited no
      significant differences with the control group. This reveals that the dietary
      fiber functional cookies made by this formula have no acute or sub-chronic
      toxicity. In terms of physiological function, compared with the control group,
      the total cholesterol (TC) and triglycerides (TG) were 17.0-21.7% and 18.7-35.0%
      lower in mice serum of all DF cookie doses groups, respectively, but this
      difference was not significant (P>0.05). Compared with positive control group,
      the Cd(2+) and Pb(2+) excretion ratios of DF group were 27.4% and 25.2% higher,
      respectively. Thus, a conclusion has been drawn that dietary fiber functional
      cookies made by this formula have no toxic or harmful actions on animals or
      humans, and the DF food was able to decrease TC and TG concentrations to some
      extent in serum and increase excretion of Cd(2+) and Pb(2+) in Feces.

PMID- 22609426
TI  - Forced and voluntary exercise counteract insulin resistance in rats: the role of
      coping style.
AB  - There are large individual differences in the success rates of exercise
      intervention programs aimed at the prevention and treatment of obesity-related
      disorders. In the present study, we tested the hypothesis that differences in
      coping style may impact the success rates of these intervention programs. We
      tested insulin responses before and after voluntary wheel running in both passive
      (insulin resistant) Roman Low Avoidance (RLA) and proactive (insulin sensitive)
      Roman High Avoidance (RHA) rats using intravenous glucose tolerance tests
      (IVGTTs). To control for a potential difference between voluntary and forced
      exercise, we also included RLA and RHA rats that were subjected to forced
      running. We found the following: 1) when given the opportunity to run voluntarily
      in a running wheel, passive RLA rats run more than proactively than RHA rats; 2)
      voluntary exercise leads to a normalization of insulin responses during an IVGTTs
      in RLA rats; and 3) there were no behavioral and physiological differences in
      efficacy between voluntary and forced running. We conclude that exercise, both
      forced and voluntary, is a successful lifestyle intervention for the treatment of
      hyperinsulinemia, especially in individuals with a passive coping style.

PMID- 22609427
TI  - Targeting tacrolimus to deeper layers of skin with improved safety for treatment
      of atopic dermatitis-Part II: in vivo assessment of dermatopharmacokinetics,
      biodistribution and efficacy.
AB  - The objective of present investigation was to study in vivo behavior of
      tacrolimus-loaded lipid-nanoparticles (T-LN) to understand its targeting
      potential for treatment of atopic-dermatitis-(AD). T-LN have shown significantly
      improved drug penetration to deeper epidermal and dermal skin-layers than
      commercial ointment-Protopic((r)) and effectively reached target dendritic-immune
      cells, responsible for immunopathogenesis of AD. Due to enhanced penetrability of
      T-LN, it became necessary to evaluate the toxicity of the nanocarrier and the
      drug at non-target tissues. This paper evaluates dermatopharmacokinetics (DPK),
      biodistribution, efficacy and safety of T-LN in comparison to Protopic((r)) as
      reference. In vivo DPK in guinea pigs showed 3.02-fold higher bioavailability
      while gamma-scintigraphy in albino-rats demonstrated 1.5-fold rapid penetration
      of radioactivity in skin for T-LN. Biodistribution in albino-rats revealed
      restricted localization at the target-skin-area with no general spreading to
      other body organs suggesting targeting potential of T-LN. In vivo efficacy
      studies in BALB/c mice showed highly efficient suppression of inflammatory AD
      like skin-lesions with T-LN than reference and placebo. Dermal toxicity-studies
      revealed keratosis and collagenous mass-infiltration with repeated application of
      reference however interestingly, T-LN treated group showed no evident toxicity
      demonstrating significantly improved safety. Thus T-LN offered improved
      penetration to the target site without any toxic-effects and would represent an
      efficient and commercially viable alternative for AD treatment.

PMID- 22609429
TI  - Inflammatory pain disrupts the orbitofrontal neuronal activity and risk
      assessment performance in a rodent decision-making task.
AB  - It has been recently described that disruption of the neural mechanisms of
      emotion-based decision making occurs in both chronic pain patients and in animal
      models of pain; moreover, it also has been shown that chronic pain causes
      morphological and functional changes in the prefrontal cortex that may be crucial
      for this decision-making dysfunction. However, it is not known whether pain alone
      is capable of altering the neuronal encoding of decision exhibited by prefrontal
      neurons. We have previously shown that naive animals have risk-averse performance
      in the rodent gambling task, whereas chronic pain animals reverse their choice
      preference and become risk prone. Using this paradigm, we chronically implanted
      arrays of multielectrodes and recorded from neuronal ensembles in the
      orbitofrontal cortex of freely moving animals performing 4 sessions of the rodent
      gambling task: 2 in control conditions and 2 after the onset of inflammatory pain
      induced by complete Freund's adjuvant injection. Our results show that the
      instantaneous neuronal firing rate was correlated with the probability of
      choosing a specific lever in 62.5% of the neurons; however, although in the
      control sessions 61% of the neurons encoded the reward magnitude, after the pain
      onset only 16% of the neurons differentiated small from large rewards. Moreover,
      we found that the fraction of risk-sensitive neurons recorded in each session
      predicted the overall risk bias of the animal. Our data suggest that
      orbitofrontal cortex encoding of risk preference is compromised in chronic pain
      animals.

PMID- 22609430
TI  - EVENDOL, a new behavioral pain scale for children ages 0 to 7 years in the
      emergency department: design and validation.
AB  - Numerous behavioral pain measures have been validated for young children, but
      none is appropriate to assess pain in emergency departments (EDs), where
      caregivers need a simple, easily completed scale. Our objective was to elaborate
      and validate a tool, relevant in any painful situation, with agitation or
      prostration, and for any age under 7 years. Five items (scored 0 to 3) were
      developed by pediatric pain and emergency caregivers. The new scale, called
      EVENDOL, was tested at children's arrival and after analgesics, at rest, and
      during mobilization. The validation study included 291 children from birth to 7
      years old in 4 French EDs, and independent observations by the ED nurse and a
      researcher. The Cronbach coefficient was excellent (0.83 to 0.92). Construct
      validity was demonstrated by a decrease in scores after nalbuphine: 8.14 to 3.62
      of 15 at rest (P<.0001), 11.87 to 6.65 at mobilization (P = .0011); by good
      correlations between EVENDOL and nurse or researcher numerical scores: 0.79 to
      0.92 (P<.0001); by good correlations between children's self-assessment scores
      and EVENDOL in children ages 4 to 7 (0.64 to 0.93). Discriminant validity with
      tiredness, anxiety, and hunger was good. Interrater reliability was excellent
      between nurses and researcher (weighted kappa 0.7 to 0.9), and in a group of 6
      nurses (simultaneous assessment of 122 videos). The treatment threshold was
      determined at 4 of 15. EVENDOL has excellent validity and can be used for all
      children under age 7 in EDs, for any age and any pain, acute as well as more
      prolonged.

PMID- 22609428
TI  - Functional interactions between NMDA receptors and TRPV1 in trigeminal sensory
      neurons mediate mechanical hyperalgesia in the rat masseter muscle.
AB  - The NMDA and TRPV1 receptors that are expressed in sensory neurons have been
      independently demonstrated to play important roles in peripheral pain mechanisms.
      In the present study, we investigated whether the 2 receptor-channel systems form
      a functional complex that provides the basis for the development of mechanical
      hyperalgesia. In the masseter muscle, direct application of NMDA induced a time
      dependent increase in mechanical sensitivity, which was significantly blocked
      when the muscle was pretreated with a specific TRPV1 antagonist, AMG9810. The NR1
      subunit of the NMDA receptor and TRPV1 were coexpressed in 32% of masseter
      afferents in trigeminal ganglia (TG). Furthermore, NR1 and NR2B formed protein
      protein complexes with TRPV1 in TG as demonstrated by coimmunoprecipitation
      experiments. Calcium imaging analyses further corroborated that NMDA and TRPV1
      receptors functionally interact. In TG culture, application of NMDA resulted in
      phosphorylation of serine, but not threonine or tyrosine, residues of TRPV1 in a
      time course similar to that of the development of NMDA-induced mechanical
      hyperalgesia. The NMDA-induced phosphorylation was significantly attenuated by
      CaMKII and PKC inhibitors, but not by a PKA inhibitor. Consistent with the
      biochemical data, the NMDA-induced mechanical hyperalgesia was also effectively
      blocked when the muscle was pretreated with a CaMKII or PKC inhibitor. Thus, NMDA
      receptors and TRPV1 functionally interact via CaMKII and PKC signaling cascades
      and contribute to mechanical hyperalgesia. These data offer novel mechanisms by
      which 2 ligand-gated channels in sensory neurons interact and reinforce the
      notion that TRPV1 functions as a signal integrator under pathological conditions.

PMID- 22609431
TI  - A body-part-specific impairment in the visual recognition of actions in chronic
      pain patients.
AB  - Most people suffer musculoskeletal pain sometime in their lives. Although the
      pain usually disappears with the healing, it may become chronic. Recent evidence
      suggests that high-level cortical representations play a role in chronic pain.
      Here we hypothesized that the sensorimotor representations of the affected body
      parts are specifically inhibited with chronic pain. Thus, if these
      representations are not accessible for the actions performed by one's own body,
      neither should they be for the perception of actions performed by others. Chronic
      pain patients are often focused on possibly painful movements, but visual
      processes are not affected by chronic pain, so we expected that patients should
      have no problems recognizing point-light biological motion displays, but should
      be unable to extract detailed somatosensory and motor information from such
      displays. Indeed, we found that patients had no difficulty perceiving point-light
      biological motion, and were not impaired in judging manipulated weight from
      movements they would be able to perform. However, patients with chronic shoulder
      pain were specifically impaired to judge the weight from observed manual transfer
      movements, whereas chronic low-back pain patients were specifically impaired for
      trunk-rotation movements. This result gives important new insights into chronic
      pain. Also, this new impairment of biological motion perception is unique in that
      it is unrelated to visual deficits.

PMID- 22609433
TI  - Using the random walk model for understanding aging: Comments on "The quadratic
      hazard model for analyzing longitudinal data on aging, health, and the life span"
      by A.I. Yashin et al.

PMID- 22609432
TI  - Protein disulfide isomerase-associated 6 is an ATF6-inducible ER stress response
      protein that protects cardiac myocytes from ischemia/reperfusion-mediated cell
      death.
AB  - Proper folding of secreted and transmembrane proteins made in the rough
      endoplasmic reticulum (ER) requires oxygen for disulfide bond formation.
      Accordingly, ischemia can impair ER protein folding and initiate the ER stress
      response, which we previously showed is activated in the ischemic heart and in
      culture cardiac myocytes subjected to simulated ischemia. ER stress and ischemia
      activate the transcription factor, activating transcription factor 6 (ATF6),
      which induces numerous genes, many of which have not been identified, or examined
      in the heart. Using an ATF6 transgenic mouse model, we previously showed that
      ATF6 protected the heart from ischemic damage; however, the mechanism of this
      protection remains to be determined. In this study, we showed that, in the mouse
      heart, and in cultured cardiac myocytes, ATF6 induced the protein disulfide
      isomerase associated 6 (PDIA6) gene, which encodes an ER enzyme that catalyzes
      protein disulfide bond formation. Moreover, in cultured cardiac myocytes, ER
      stress-mediated PDIA6 promoter activation was ATF6-dependent, and required an ER
      stress response element (ERSE) and a nearby CCAAT box element. Electromobility
      shift assays and chromatin immunoprecipitation showed that ATF6 bound to the ERSE
      in the PDIA6 promoter, in vitro, and in the mouse heart, in vivo. Gain- and loss
      of-function studies showed that PDIA6 protected cardiac myocytes against
      simulated ischemia/reperfusion-induced death in a manner that was dependent on
      the catalytic activity of PDIA6. Thus, by facilitating disulfide bond formation,
      and enhanced ER protein folding, PDIA6 may contribute to the protective effects
      of ATF6 in the ischemic mouse heart.

PMID- 22609434
TI  - What about a theory?: Comment on "Nanopores: A journey towards DNA sequencing" by
      Meni Wanunu.

PMID- 22609435
TI  - The Gompertz law of mortality and longitudinal data: Comment on "The quadratic
      hazard model for analyzing longitudinal data on aging, health, and the life span"
      by Yashin, Arbeev, Akushevich, Kulminski, Ukraintseva, Stallard & Land.

PMID- 22609436
TI  - An innovative method for the non-destructive identification of photodegradation
      products in solid state: 1H-14N NMR-NQR and DFT/QTAIM study of photodegradation
      of nifedipine (anti-hypertensive) to nitrosonifedipine (potential anti
      oxidative).
AB  - Stability of the antihypertensive drug nifedipine (NIF) has been studied
      experimentally in solid state by (1)H-(14)N NMR-NQR double resonance (NQDR) and
      theoretically by the Density Functional Theory (DFT). Photodegradation of NIF to
      its metabolite in vivo nitrosonifedipine, NO-NIF (antioxidative agent) upon long
      term daylight exposure was detected and the changes in the molecular structure of
      NIF were analysed. The photoconversion of NIF to NO-NIF in solid was found to be
      accompanied with the electron density redistribution at nitrogen sites (NH to N
      and NO(2) to NO) and proved to be successfully detected with identification of
      photoproducts by (1)H-(14)N NQDR and DFT methods. The increase in the e(2)qQ/h
      and eta describing EFG tendency towards non-spherical symmetry was significantly
      greater upon the reduction of NO(2) site than upon hydrogen abstraction from NH
      site. The level of sensitivity of detection of the photodegradation product was
      about 1% of the original sample. The Quantum Theory of Atoms in Molecules (QTAIM)
      analysis has been found useful in predicting photoreactive sites in the molecules
      and finding the explanation of differences in reactivity between parent NIF and
      its photoproduct NO-NIF. Using NIF as a model, this study demonstrates the
      suitability of NQDR supported by DFT for non-destructive determination of the
      photodegradation products in solid state.

PMID- 22609437
TI  - Identifying antigenicity-associated sites in highly pathogenic H5N1 influenza
      virus hemagglutinin by using sparse learning.
AB  - Since the isolation of A/goose/Guangdong/1/1996 (H5N1) in farmed geese in
      southern China, highly pathogenic H5N1 avian influenza viruses have posed a
      continuous threat to both public and animal health. The non-synonymous mutation
      of the H5 hemagglutinin (HA) gene has resulted in antigenic drift, leading to
      difficulties in both clinical diagnosis and vaccine strain selection.
      Characterizing H5N1's antigenic profiles would help resolve these problems. In
      this study, a novel sparse learning method was developed to identify antigenicity
      associated sites in influenza A viruses on the basis of immunologic data sets
      (i.e., from hemagglutination inhibition and microneutralization assays) and HA
      protein sequences. Twenty-one potential antigenicity-associated sites were
      identified. A total of 17 H5N1 mutants were used to validate the effects of 11 of
      these predicted sites on H5N1's antigenicity, including 7 newly identified sites
      not located in reported antibody binding sites. The experimental data confirmed
      that mutations of these tested sites lead to changes in viral antigenicity,
      validating our method.

PMID- 22609438
TI  - Crystal structure of rice Rubisco and implications for activation induced by
      positive effectors NADPH and 6-phosphogluconate.
AB  - The key enzyme of plant photosynthesis, D-ribulose 1,5-bisphosphate
      carboxylase/oxygenase (Rubisco), must be activated to become catalytically
      competent via the carbamylation of Lys201 of the large subunit and subsequent
      stabilization by Mg(2+) coordination. Many biochemical studies have reported that
      reduced nicotinamide adenine dinucleotide phosphate (NADPH) and 6
      phosphogluconate (6PG) function as positive effectors to promote activation.
      However, the structural mechanism remains unknown. Here, we have determined the
      crystal structures of activated rice Rubisco in complex with NADPH, 6PG, or 2
      carboxy-D-arabinitol 1,5-bisphosphate (2CABP). The structures of the NADPH and
      6PG complexes adopt open-state conformations, in which loop 6 at the catalytic
      site and some other loops are disordered. The structure of the 2CABP complex is
      in a closed state, similar to the previous 2CABP-bound activated structures from
      other sources. The catalytic sites of the NADPH and 6PG complexes are fully
      activated, despite the fact that bicarbonate (NaHCO(3)) was not added into the
      crystallization solution. In the catalytic site, NADPH does not interact with
      Mg(2+) directly but interacts with Mg(2+)-coordinated water molecules, while 6PG
      interacts with Mg(2+) directly. These observations suggest that the two effectors
      promote Rubisco activation by stabilizing the complex of Mg(2+) and the
      carbamylated Lys201 with unique interactions and preventing its dissociation. The
      structure also reveals that the relaxed complex of the effectors (NADPH or 6PG),
      distinct from the tight-binding mode of 2CABP, would allow rapid exchange of the
      effectors in the catalytic sites by substrate D-ribulose 1,5-bisphosphate for
      catalysis in physiological conditions.

PMID- 22609439
TI  - A cellulolytic Hypocrea strain isolated from South American brave straw produces
      a modular xylanase.
AB  - Cellulase-producing fungi from the Andean regions in Bolivia, an ecosystem
      characterized as an extreme arid highland, were studied. Thirty-two isolates were
      screened for presence of cellulase activity using carboxymethyl cellulose (CMC)
      as carbon source, and activity was confirmed using a filter paper assay. One
      isolate, denoted as BLT1C was selected from this screening, and sequence analysis
      of the internal transcribed spacer (ITS) classified the strain as Hypocrea lixii.
      The secretome of BLT1C showed high xylanase activity (compared to that of two
      reference Trichoderma reesei strains) when cultivated using brave straw, an
      abundant native grass from the area, as carbon source. SDS-PAGE analysis revealed
      three main protein-bands (18, 32 and 65 kDa) and in-gel digestion and mass
      spectrometry combined with activity analysis showed that these proteins were
      active xylanases with molecular masses corresponding to (I) a single glycoside
      hydrolase family 11 catalytic module (18 kDa), and (II, III) modular enzymes,
      with the GH11 catalytic domain connected to a module of unknown function (32 kDa)
      or putatively connected to a GH7 catalytic module (65 kDa). The N-terminal
      sequence of the 65 kDa xylanase did not show significant sequence similarities to
      deposited sequences. The collected data on xylanase activity, molecular mass,
      GH11-sequence conservation, combined with lack of sequence similarities in the N
      terminus show that the 65 kDa band corresponds to a novel modular xylanase.

PMID- 22609440
TI  - Potent inhibition of starch-synthase by Tris-type buffers is responsible for the
      perpetuation of the primer myth for starch biosynthesis.
AB  - Mukerjea and Robyt [Carbohydr. Res. 2012, 352, 137-142] showed that a primer-free
      potato starch-synthase synthesized starch chains de novo, without the addition of
      a primer. A dichotomy arises as to why 61 studies from 1964 to the present have
      had to add a carbohydrate primer to obtain starch-synthase activity. All of these
      studies used 25-100 mM Tris, Bicine, or Tricine buffers. We have found that the
      Tris-type buffers completely inhibit starch-synthase at these concentrations. The
      addition of 10 mg/mL of the putative primers, glycogen and maltotetraose, gave a
      partial reversal of the inhibition, with glycogen being better than
      maltotetraose. It has been found that the Tris-type buffers form a complex with
      the ADPGlc substrate, removing it from the digest, causing the inhibition. The
      addition of the putative primers releases some of the ADPGlc from the complex,
      permitting it to act as a substrate for starch-synthase. The study definitively
      shows that the need for primers for starch-synthase by many investigators from
      1964 to the present has been caused by Tris-type buffer inhibition that was
      partially reversed by putative primers. This has led to the perpetuation of the
      primer myth for the biosynthesis of starch chains by starch-synthase.

PMID- 22609441
TI  - Isolation, characterization and total regioselective synthesis of the novel MUO
      conotoxin MfVIA from Conus magnificus that targets voltage-gated sodium channels.
AB  - The MUO-conotoxins are notable for their unique selectivity for Na(v)1.8 over
      other sodium channel isoforms, making them attractive drug leads for the
      treatment of neuropathic pain. We describe the discovery of a novel MUO
      conotoxin, MfVIA, from the venom of Conus magnificus using high-throughput
      screening approaches. MfVIA was found to be a hydrophobic 32-residue peptide
      (amino acid sequence RDCQEKWEYCIVPILGFVYCCPGLICGPFVCV) with highest sequence
      homology to MUO-conotoxin MrVIB. To overcome the synthetic challenges posed by
      MUO-conotoxins due to their hydrophobic nature and difficult folding, we
      developed a novel regioselective approach for the synthesis of MUO-conotoxins.
      Performing selective oxidative deprotections of the cysteine side-chain
      protecting groups of the fully protected peptide allowed manipulations in organic
      solvents with no chromatography required between steps. Using this approach, we
      obtained correctly folded MfVIA with increased synthetic yields. Biological
      activity of MfVIA was assessed using membrane potential-sensitive dyes and
      electrophysiological recording techniques. MfVIA preferentially inhibits Na(v)1.8
      (IC50 95.9+/-74.3 nM) and Na(v)1.4 (IC50 81+/-16 nM), with significantly lower
      affinity for other Na(v) subtypes (IC50 431-6203 nM;
      Na(v)1.5>1.6~1.7~1.3~1.1~1.2). This improved approach to MUO-conotoxin synthesis
      will facilitate the optimization of MUO-conotoxins as novel analgesic molecules
      to improve pain management.

PMID- 22609442
TI  - Polymorphisms of genes related to endothelial cells are associated with primary
      biliary cirrhosis patients of Cretan origin.
AB  - BACKGROUND: Primary biliary cirrhosis (PBC) is an organ specific autoimmune
      disease of still unidentified genetic etiology. We have shown that endothelins
      (ETs), produced by the liver endothelial cells are increased in PBC and may play
      a major pathogenetic role. AIMS: To study gene polymorphisms related to the
      endothelial cells (eNOS, EDN-1 genes) and, to investigate whether the previously
      reported association of CTLA4 gene polymorphisms is replicated in a genetically
      homogeneous Greek population. PATIENTS AND METHODS: Genomic DNA was extracted
      from 100 PBC patients (83 females, 93% AMA+, 74/100 Ludwig stage I-II) and 158
      healthy controls. eNOS, CTLA4 and ET1 polymorphisms were determined by PCR-RFLPs
      analysis. RESULTS: Both eNOS intron4 VNTR and eNOS exon7 G894T SNP were
      significantly associated with increased risk in PBC. EDN-11 rs2071942 "A" and
      rs5370 "T" alleles appeared a tendency for association with disease progression.
      No association was found between PBC and the CTLA4 SNPs analyzed. CONCLUSIONS: We
      demonstrated that eNOS, a gene related to the liver endothelium function is
      associated with PBC. Contrarily, the important in adaptive immunity gene CTLA4
      was not associated with the disease in the homogeneous population analyzed. These
      results are compatible partially with our previous hypothesis that defects of the
      liver endothelial system, leading to endothelin overproduction, may be a
      fundamental early pathogenetic mechanism in PBC.

PMID- 22609443
TI  - In contrast to HIV, KIR3DS1 does not influence outcome in HTLV-1 retroviral
      infection.
AB  - While most carriers of human T-cell leukemia virus type 1 (HTLV-1) remain
      asymptomatic throughout their lifetime, infection is associated with the
      development of adult T-cell leukemia (ATL) and HTLV-1-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP). The exact parameters that
      determine these outcomes are unknown but are believed to include host genetic
      factors that control the immune response to infection. Host response to fellow
      retroviridae member HIV is influenced by the expression of members of the Killer
      Immunoglobulin Receptor (KIR) family including KIR3DS1. In this study we examined
      the association of KIR3DS1 with the outcome of HTLV-1 infection in three
      geographically distinct cohorts (Jamaican, Japanese and Brazilian). Despite
      increased prevalence of KIR3DS1 in the HAM/TSP patients of the Jamaican cohort,
      we found no evidence for a role of KIR3DS1 in influencing control of proviral
      load or disease outcome. This suggests that unlike HIV, KIR3DS1-mediated
      regulation of HTLV-1 infection does not occur, or is ineffective.

PMID- 22609444
TI  - MICB polymorphism in a southern Chinese Han population: the identification of two
      new MICB alleles, MICB*005:06 and MICB*026.
AB  - In this study, we investigated the major histocompatibility complex (MHC) class I
      chain-related gene B (MICB) allelic variation by sequence-based typing (SBT) in
      201 healthy, unrelated Han subjects from Hunan province, southern China. Eleven
      MICB alleles were observed, among which MICB(*)005:02 predominated with a
      frequency of 64.93%. Significant linkage disequilibrium (LD) was observed for 5
      HLA-B-MICB and 6 MICA-MICB haplotypes. Compared with a northern Chinese Han
      population, several MICB-containing haplotypes appeared to be highly specific to
      this southern Chinese Han population. Two new MICB alleles, MICB(*)005:06 and
      MICB(*)026, were identified. Aligned with MICB(*)005:02, MICB(*)005:06 has a
      synonymous T replacement at nucleotide 762 in exon 4; MICB(*)026 has probably
      arisen from MICB(*)004:01 through a single nucleotide substitution from G to A at
      position 826 in exon 4, leading to an amino acid change from glutamic acid to
      lysine at codon 253. HLA-A(*)02-C(*)01-B(*)46-MICA(*)010-MICB(*)005:02-DRB1(*)09
      was the most prevalent six-locus haplotype with a frequency of 8.49%. HLA-A(*)30
      C(*)06-B(*)13:02-MICA(*)008:01-MICB(*)005:02-DRB1(*)07 appeared to be a conserved
      extended haplotype. Our results provide new information about MICB genetic
      polymorphism in Chinese Han populations, and will inform future studies of the
      potential role of MICB in allogeneic organ transplantation and disease
      susceptibility in related ethnic groups.

PMID- 22609445
TI  - Pathway analysis of genome-wide association studies on uric acid concentrations.
AB  - OBJECTIVE: The aims of this study were to identify the candidate causal single
      nucleotide polymorphisms (SNPs) and candidate causal mechanisms influencing uric
      acid level and to generate hypotheses for the SNP to gene to pathways that
      influence uric acid concentrations. METHODS: Meta-analysis data of 954 SNPs with
      genome-wide significance in 14 genome-wide association studies (GWASs) comprising
      28,141 individuals of European ancestry was subjected to ICSNPathway (Identify
      candidate Causal SNPs and Pathways) analysis to establish associations between
      pathways and uric acid concentrations. RESULTS: ICSNPathway analysis identified
      14 candidate causal SNPs, five genes, and two candidate causal pathways, which
      provided two hypothetical biologic mechanisms: (1) rs2728121 (regulatory region)
      to polycystic kidney disease 2 (PKD2) to ion transmembrane transporter activity;
      (2) rs942377, rs3799346, rs3799344, rs2762353, rs13197601, rs3757131, rs1165215,
      rs1165196 to SLC17A1 to ion transmembrane transporter activity and secondary
      active transmembrane transporter activity. SLC17A1, SLC17A3, SLC17A4, SLC22A11,
      and SLC2A9 were involved in both pathways, and PKD2 and SLC16A9 in one pathway.
      CONCLUSION: By applying ICSNPathway analysis to GWAS data on uric acid levels, 14
      SNPs, five genes, and two pathways involving the PKD2, SLC17A1, SLC17A3, SLC17A4,
      and SLC2A9 genes were identified that might contribute to the condition in
      Europeans.

PMID- 22609446
TI  - The aryl hydrocarbon receptor (AhR) ligand VAF347 selectively acts on monocytes
      and naive CD4(+) Th cells to promote the development of IL-22-secreting Th cells.
AB  - The low molecular weight compound VAF347, and its pro-drug version VAG539,
      interact with the transcription factor aryl hydrocarbon receptor (AhR) on
      monocytes to mediate its anti-inflammatory activity in vitro and in vivo. AhR is
      a crucial factor for IL-22 production, which regulates skin and gut homeostasis.
      Here we investigated whether VAF347 might control the differentiation of naive T
      cells into IL-22-secreting cells and/or regulate IL-22 production by memory T
      cells. Human monocytes exposed to VAF347 differentiated into dendritic cells
      capable of instructing a naive CD4(+) T cell differentiation program that
      promoted IL-22 secretion and concomitantly inhibited IL-17 production. Whilst AhR
      ligation by VAF347 on naive CD4(+) T cells favored the development of single IL
      22-secreting cells (Th22), it suppressed the generation of T cells secreting
      either IL-22 and IFN-gamma or IL-17 and IFN-gamma. In contrast, memory T cells
      were refractory to AhR regulation since VAF347, AhR antagonist or AhR gene
      silencing did not modulate the production of any of these cytokines. Interfering
      with AhR functions using VAF347 may provide an efficient way to intervene with
      autoimmune disease since it would enhance the host protective function mediated
      by IL-22 while preventing the development of Th cells secreting pro-inflammatory
      cytokines.

PMID- 22609447
TI  - Chemometrics and vibrational spectroscopy as green tools for mine
      phytoremediation strategies.
AB  - This study describes the use of near infrared (NIR) spectroscopy in combination
      with chemometrics to characterise Combretum erythrophyllum plant material to
      determine differences in the chemical profiles of samples harvested from mine
      contaminated areas and those of natural populations. The chemometric computation
      of near infrared vibrational spectra was used to generate principal component
      analysis and partial least squares models. These models were used to determine
      seasonal differences in the chemical matrices of samples harvested from the mine
      sites with different levels of contamination. Principal component analysis
      scatter plots illustrated clustering of phenolic profiles of samples depending on
      whether they originated from contaminated or uncontaminated soils. A partial
      least squares model was developed to link the variations in the chemical
      composition and levels of contamination in all samples collected in the same
      season (autumn). The levels of total soluble phenolic compounds in leaf extracts
      of C. erythrophyllum were measured using the Folin-Ciocalteau assay. Data
      analysis of the samples revealed that plants harvested from mine sites,
      particularly in summer, produced a higher level of phenolic compounds than those
      of the natural population, thereby displaying a good correlation with the
      chemometric models.

PMID- 22609449
TI  - Urotensin II protects ischemic reperfusion injury of hearts through ROS and
      antioxidant pathway.
AB  - Urotensin II (UII) is a vasoactive peptide which is bound to a G protein-coupled
      receptor. UII and its receptor are upregulated in ischemic and chronic hypoxic
      myocardium, but the effect of UII on ischemic reperfusion (I/R) injury is still
      controversial. The aim of the present study was to investigate whether UII
      protects heart function against I/R injury. Global ischemia was performed using
      isolated perfused Langendorff hearts of Sprague-Dawley rats. Hearts were perfused
      with Krebs-Henseleit buffer for 20min pre-ischemic period followed by a 20min
      global ischemia and 50min reperfusion. Pretreatment with UII (10nM) for 10min
      increased recovery percentage of the post-ischemic left ventricular developed
      pressure and +/-dp/dt, and decreased post-ischemic left ventricular end-diastolic
      pressure as compared with I/R group. UII decreased infarct size and an increased
      lactate dehydrogenase level during reperfusion. Cardioprotective effects of UII
      were attenuated by pretreatment with UII receptor antagonist. The hydrogen
      peroxide activity was increased in UII-treated heart before ischemia. The Mn-SOD,
      catalase, heme oxygenase-1 and Bcl-2 levels were increased, and the Bax and
      caspase-9 levels were decreased in UII-treated hearts. These results suggest that
      UII has cardioprotective effects against I/R injury partly through activating
      antioxidant enzymes and reactive oxygen species.

PMID- 22609448
TI  - Small peptide functionalized thiol-ene hydrogels as culture substrates for
      understanding valvular interstitial cell activation and de novo tissue
      deposition.
AB  - A thiol-ene polymerization platform was used to synthesize peptide functionalized
      poly(ethylene glycol) hydrogels, which were initially characterized and compared
      to theoretical predictions of Young's modulus via a theoretical crosslinking
      density equation presented herein. After thorough characterization, this material
      system's utility for answering specific biological hypotheses was demonstrated
      with the culture and observation of aortic valvular interstitial cells (VICs).
      Specifically, these materials were used to better understand the role of
      substrate elasticity and biochemical functionality on VIC alpha-smooth muscle
      (alphaSMA) expression and secretory properties (i.e. de novo extracellular matrix
      (ECM)). The Young's moduli of the hydrogels varied from 28kPa (activating, 90%
      myofibroblasts) to 4kPa (non-activating, 15% myofibroblast), and the biochemical
      functionality was tailored by incorporating three small adhesive peptide
      sequences, RGDS, VGVAPG and P15. To promote VIC adhesion, a basal [RGDS] of 0.8mM
      was used in all formulations, while the [VGVAPG] or [P15] were varied to be lower
      than, equal to or higher than 0.8mM. The substrates with 1.2mM VGVAPG and all
      gels with P15 led to significantly higher alphaSMA expression for both stiff and
      soft substrates, as compared to 0.8mM RGDS alone. Importantly, all gel conditions
      alphaSMA expression were significantly lower than tissue culture poly(styrene)
      (TCPS; ~4- to 10-fold difference). The ECM produced decreased significantly as
      the total integrin-binding peptide concentration increased, but was significantly
      higher than that produced on TCPS. This easily tailored material system provides
      a useful culture platform to improve the fundamental understanding of VIC biology
      through isolating specific biological cues and observing VIC function.

PMID- 22609450
TI  - Arresting cancer proliferation by controlling the surface crystallinity of carbon
      materials without generating reactive oxygen species.
AB  - This study demonstrated that the surface crystallinity of carbon nanostructures
      is an additional independent factor that should be considered for the inhibition
      of cancer proliferation without activating reactive oxygen species (ROS). In
      addition, cytotoxic evaluation of both proliferating cancer cells and fully
      differentiated nerve cells (i.e. non-proliferative) showed selective
      cytotoxicity: single-walled and highly crystalline carbon nanostructures
      aggressively inhibited the proliferation of glioma cancer cells, but exhibited no
      notable cytotoxicity effects on differentiated nerve cells. Although single-wall
      carbon nanotubes have been shown to elicit potent proinflammatory responses by
      means of trigger ROS, our results demonstrated that highly crystalline carbon
      structures can be utilized as a selective antiproliferative agent against brain
      tumor cells without increasing the ROS level and without significant cytotoxic
      effects to adjacent nerve cells.

PMID- 22609451
TI  - A prototype tissue engineered blood vessel using amniotic membrane as scaffold.
AB  - In this study, we used amniotic membrane (AM), a natural extracellular matrix, as
      a scaffold for the fabrication of tissue engineered blood vessels (TEBVs). The
      inner surface of the denuded glutaraldehyde cross-linked AM tube was
      endothelialized with porcine vascular endothelial cells (ECs) and subjected to a
      physiological (12 dynecm(-2)) shear stress (SS) for 2 and 4 days. The results
      showed that after applying SS, an intact EC monolayer was maintained in the lumen
      surface of the TEBV. The ECs were aligned with their long axis parallel to the
      blood flow. The immunofluorescent microscopy showed that the intercellular
      junctional proteins, PECAM-1 and VE-cadherin, were surrounding the EC periphery
      and were better developed and more abundant in SS-treated TEBVs than the static
      controls. The Western blot indicated that the expressions of PECAM-1 and VE
      cadherin were increased by 72 +/- 9% and 67 +/- 7%, respectively, after shear
      stress treatment. The distribution pattern of integrin beta1 was mainly at the
      interface of ECs and AM in static TEBVs but it was extended to the cell-cell
      junctions after SS treatment. The SS promoted the expression of integrin
      alpha(v)beta(3) without altering its distribution in TEBV. The results suggest
      that glutaraldehyde cross-linked AM tube can potentially be used as a scaffold
      biomaterial for TEBV fabrication. Most importantly, the use of an AM tube
      shortened the TEBV fabrication.

PMID- 22609452
TI  - Multi-scale classification of disease using structural MRI and wavelet transform.
AB  - Recently, multivariate analysis algorithms have become a popular tool to diagnose
      neurological diseases based on neuroimaging data. Most studies, however, are
      biased for one specific scale, namely the scale given by the spatial resolution
      (i.e. dimension) of the data. In the present study, we propose to use the dual
      tree complex wavelet transform to extract information on different spatial scales
      from structural MRI data and show its relevance for disease classification. Based
      on the magnitude representation of the complex wavelet coefficients calculated
      from the MR images, we identified a new class of features taking scale,
      directionality and potentially local information into account simultaneously. By
      using a linear support vector machine, these features were shown to discriminate
      significantly between spatially normalized MR images of 41 patients suffering
      from multiple sclerosis and 26 healthy controls. Interestingly, the decoding
      accuracies varied strongly among the different scales and it turned out that
      scales containing low frequency information were partly superior to scales
      containing high frequency information. Usually, this type of information is
      neglected since most decoding studies use only the original scale of the data. In
      conclusion, our proposed method has not only a high potential to assist in the
      diagnostic process of multiple sclerosis, but can be applied to other diseases or
      general decoding problems in structural or functional MRI.

PMID- 22609453
TI  - Biological parametric mapping accounting for random regressors with regression
      calibration and model II regression.
AB  - Massively univariate regression and inference in the form of statistical
      parametric mapping have transformed the way in which multi-dimensional imaging
      data are studied. In functional and structural neuroimaging, the de facto
      standard "design matrix"-based general linear regression model and its multi
      level cousins have enabled investigation of the biological basis of the human
      brain. With modern study designs, it is possible to acquire multi-modal three
      dimensional assessments of the same individuals--e.g., structural, functional and
      quantitative magnetic resonance imaging, alongside functional and ligand binding
      maps with positron emission tomography. Largely, current statistical methods in
      the imaging community assume that the regressors are non-random. For more
      realistic multi-parametric assessment (e.g., voxel-wise modeling), distributional
      consideration of all observations is appropriate. Herein, we discuss two unified
      regression and inference approaches, model II regression and regression
      calibration, for use in massively univariate inference with imaging data. These
      methods use the design matrix paradigm and account for both random and non-random
      imaging regressors. We characterize these methods in simulation and illustrate
      their use on an empirical dataset. Both methods have been made readily available
      as a toolbox plug-in for the SPM software.

PMID- 22609454
TI  - Subcellular distribution and toxicity of cadmium in Potamogeton crispus L.
AB  - The submerged macrophyte Potamogeton crispus L. was subjected to varying doses of
      cadmium (0, 20, 40, 60 and 80 MUM) for 7 d, and the plants were analyzed for
      subcellular distribution of Cd, accumulation of mineral nutrients,
      photosynthesis, oxidative stress, protein content, and ultrastructural
      distribution of calcium (Ca). Leaf fractionation by differential centrifugation
      indicated that 48-69% of Cd was accumulated in the cell wall. At all doses of Cd,
      the levels of Ca and B rose and the level of Mn fell; the levels of Fe, Mg, Zn,
      Cu, Mo, and P rose initially only to decline later. Exposure to Cd caused
      oxidative stress as evident by increased content of malondialdehyde and decreased
      contents of chlorophyll and protein. Photosynthetic efficiency, as indicated by
      the quenching of chlorophyll a fluorescence (Fv/Fm, Fo and Fm), decreased
      significantly, the extent of decrease being directly proportional to the
      concentration of Cd. Increased amounts of precipitates of calcium were noticed in
      the treated plants, located either outside the cell membrane or in chloroplasts,
      mitochondria, the nucleus, and the cytoplasm whereas control plants showed small
      deposits of the precipitates around surface of the vacuole membrane and in the
      intercellular space but rarely in the cytoplasm. Photosynthetic efficiency and
      oxidative stress could be used as indicators of physiological end-points in
      determining the extent of Cd phytotoxicity.

PMID- 22609455
TI  - Norcantharidin enhances ABT-737-induced apoptosis in hepatocellular carcinoma
      cells by transcriptional repression of Mcl-1.
AB  - Small-molecule cell-permeable Bcl-2/Bcl-xL antagonist ABT-737 has recently
      emerged as a novel cancer therapeutic agent because it potently induces apoptosis
      in certain cancer cells. However, since ABT-737 binds to Mcl-1 with low affinity,
      ABT-737-mediated apoptosis signaling is inhibited in hepatocellular carcinoma
      (HCC) cells and other solid cancer cells due to the elevated expression of Mcl-1.
      Accordingly, strategies that target Mcl-1 are explored for overcoming ABT-737
      resistance. In this study, we reported that Norcantharidin (NCTD), a small
      molecule anticancer drug derived from Chinese traditional medicine blister beetle
      (Mylabris), induced transcriptional repression of Mcl-1 and considerably enhanced
      ABT-737-triggered cell viability inhibition and apoptosis in multiple HCC cell
      lines. Moreover, we observed that the enhancement of ABT-737-mediated apoptosis
      by NCTD was associated with activation of mitochondrial apoptosis signaling
      pathway, which involved cytosolic release of cytochrome c, cleavage of caspase-9
      and caspase-3. Additionally, knockdown of Bax/Bak, the key effectors
      permeabilizing mitochondrial outer membrane significantly attenuated the
      enhancement, indicating mitochondrial apoptosis pathway played an essential role
      in the execution of the apoptosis. Finally, knockdown of Mcl-1 substantially
      potentiated ABT-737-mediated apoptotic cell death, confirming the potency of Mcl
      1 repression by NCTD in enhancing ABT-737-induced apoptosis. These results
      therefore suggest that combination treatment with NCTD can overcome ABT-737
      resistance and enhance ABT-737 therapeutic efficacy in treating human HCC.

PMID- 22609456
TI  - Catalase plays a key role in salt stress acclimation induced by hydrogen peroxide
      pretreatment in maize.
AB  - Pretreatment in plants is recognized as a valuable strategy to stimulate plant
      defenses, leading to better plant development. This study evaluated the effects
      of H2O2 leaf spraying pretreatment on plant growth and investigated the
      antioxidative mechanisms involved in the response of maize plants to salt stress.
      It was found that salinity reduced maize seedling growth when compared to control
      conditions, and H2O2 foliar spraying was effective in minimizing this effect.
      Analysis of the antioxidative enzymes catalase (EC 1.11.1.6), guaiacol peroxidase
      (EC 1.11.1.7), ascorbate peroxidase (EC 1.11.1.1) and superoxide dismutase (EC
      1.15.1.1) revealed that H2O2 spraying increased antioxidant enzyme activities.
      Catalase (CAT) was the most responsive of these enzymes to H2O2, with higher
      activity early (48 h) in the treatment, while guaiacol peroxidase (GPX) and
      ascorbate peroxidase (APX) were responsive only at later stages (240 h) of
      treatment. Increased CAT activity appears linked to gene expression regulation.
      Lower malondialdehyde levels were detected in plants with higher CAT activity,
      which may result from the protective function of this enzyme. Overall, we can
      conclude that pretreatment with H2O2 leaf spraying was able to reduce the
      deleterious effects of salinity on seedling growth and lipid peroxidation. These
      responses could be attributed to the ability of H2O2 to induce antioxidant
      defenses, especially CAT activity.

PMID- 22609457
TI  - Novel durum wheat genes up-regulated in response to a combination of heat and
      drought stress.
AB  - We report the effect of heat, drought and combined stress on the expression of a
      group of genes that are up-regulated under these conditions in durum wheat
      (Triticum turgidum subsp. durum) plants. Modulation of gene expression was
      studied by cDNA-AFLP performed on RNAs extracted from flag leaves. By this
      approach, we identified several novel durum wheat genes whose expression is
      modulated under different stress conditions. We focused on a group of hitherto
      undescribed up-regulated genes in durum wheat, among these, 7 are up-regulated by
      heat, 8 by drought stress, 15 by combined heat and drought stress, 4 are up
      regulated by both heat and combined stress, and 3 by both drought and combined
      stress. The functional characterization of these genes will provide new data that
      could help the developing of strategies aimed at improving durum wheat tolerance
      to field stress.

PMID- 22609458
TI  - Biochemical dissection of diageotropica and Never ripe tomato mutants to Cd
      stressful conditions.
AB  - In order to further address the modulation of signaling pathways of stress
      responses and their relation to hormones, we used the ethylene-insensitive Never
      ripe (Nr) and the auxin-insensitive diageotropica (dgt) tomato mutants. The two
      mutants and the control Micro-Tom (MT) cultivar were grown over a 40-day period
      in the presence of Cd (0.2 mM CdCl2 and 1 mM CdCl2). Lipid peroxidation, leaf
      chlorophyll, proline content, Cd content and antioxidant enzyme activities in
      roots, leaves and fruits were determined. The overall results indicated that the
      MT genotype had the most pronounced Cd damage effects while Nr and dgt genotypes
      might withstand or avoid stress imposed by Cd. This fact may be attributed, at
      least in part, to the fact that the known auxin-stimulated ethylene production is
      comprised in dgt plants. Conversely, the Nr genotype was more affected by the Cd
      imposed stress than dgt, which may be explained by the fact that Nr retains a
      partial sensitivity to ethylene. These results add further information that
      should help unraveling the relative importance of ethylene in regulating the cell
      responses to stressful conditions.

PMID- 22609459
TI  - Identification of differentially expressed genes in a spontaneous altered leaf
      shape mutant of the navel orange [Citrus sinensis (L.) Osbeck].
AB  - Most of the economically important citrus cultivars have originated from bud
      mutations. Leaf shape and structure are important factors that impact plant
      photosynthesis. We found a spontaneous bud mutant exhibiting a narrow leaf
      phenotype in navel orange [Citrus sinensis (L.) Osbeck]. To identify and
      characterize the genes involved in the formation of this trait, we performed
      suppression subtractive hybridization (SSH) and macroarray analysis. A total of
      221 non-redundant differentially expressed transcripts were obtained. These
      transcripts included cell wall- and microtubule-related genes and two
      transcription factor-encoding genes, yabby and wox, which are crucial for leaf
      morphogenesis. Many highly redundant transcripts were associated with stress
      responses, while others, encoding caffeic acid 3-O-methyltransferase (EC
      2.1.1.68) and a myb-like transcription factor, might be involved in the lignin
      pathway, which produces a component of secondary walls. Furthermore, real-time
      quantitative RT-PCR was performed for selected genes to validate the quality of
      the expressed sequence tags (ESTs) from the SSH libraries. This study represents
      an attempt to investigate the molecular mechanism associated with a leaf shape
      mutation, and its results provide new clues for understanding leaf shape
      mutations in citrus.

PMID- 22609460
TI  - Shikimate pathway modulates the elicitor-stimulated accumulation of fragrant 2
      hydroxy-4-methoxybenzaldehyde in Hemidesmus indicus roots.
AB  - Enzymatic route to fragrant 2-hydroxy-4-methoxybenzaldehyde (MBALD) formation in
      Hemidesmus indicus roots is not known. Earlier studies with H. indicus excised
      roots suggested a possible origin of MBALD via central phenylpropanoid pathway.
      Different elicitors (e.g., chitosan, methyl jasmonate, yeast extract) were tested
      for their relative efficiency in uplifting MBALD accumulation in roots, amongst
      which, treatment with yeast extract for 18 h showed maximum accumulation in
      excised roots. As benzoate pathways originate either directly from shikimate or
      via phenylpropanoid pathway, this study aimed at finding the roles of shikimate
      pathway in uplifting/enhancing MBALD accumulation in H. indicus roots upon
      elicitation. In fact, a sharp increase in shikimate dehydrogenase (SKDH; E.C.
      1.1.1.25) along with phenylalanine ammonia-lyase (PAL; E.C. 4.3.1.24) activities
      was noted on a time-course basis in yeast extract-treated roots as compared to
      the untreated ones. PAL as well as phenylpropanoid C2 side-chain cleavage
      activities (leading to p-hydroxybenzaldehyde, the first benzoate product formed
      in the MBALD pathway) were compared in elicited roots, non-elicited roots and
      glyphosate-treated elicited roots at different concentrations of glyphosate. It
      was observed that glyphosate treatment, in addition to 25% suppressions of
      phenylalanine ammonia-lyase and C2 chain-cleavage enzyme activities as compared
      to elicited one, also resulted in around 40% suppression of MBALD accumulation,
      when used in conjunction with yeast extract treatment; in contrast, shikimic acid
      content was increased as compared to glyphosate untreated ones. These findings
      suggest that shikimate pathway plays an important role in modulating MBALD
      biosynthesis in H. indicus roots.

PMID- 22609461
TI  - Modification of the lipidome in RAW264.7 macrophage subjected to stable silencing
      of oxysterol-binding proteins.
AB  - Oxysterol-binding protein homologs (ORPs) are implicated in lipid metabolism,
      vesicle transport and cell signaling. In this study we generated RAW264.7 cells
      with ORP1L, ORP3, or ORP8 silenced using shRNA lentiviruses. The lipidome of the
      cells under basal serum-free culture conditions or as treated with oxidized LDL
      (oxLDL), enzymatically modified LDL (E-LDL), or lipopolysaccharide (LPS) was
      analyzed by mass spectrometry. Reduction in each ORP resulted in distinct and
      complex effects on macrophage lipidome. Under basal conditions, ORP1L silencing
      had strongest effects on phosphatidylinositols (PI, increase), free cholesterol
      (FC, increase), and cholesteryl esters (CE, increase). ORP3 silencing affected
      most the glucosyl ceramides (GluCer, decrease) and PE-plasmalogens (PE-pl,
      decrease), while ORP8 silencing increased FC and CE, and decreased GluCer and PE
      pl. Upon LPS treatment, the ORP effects were modified: under these conditions
      ORP1L silencing caused increase of Cer, ORP3 silencing decrease of PI, and ORP8
      silencing decrease of PI and increase of PE, not detectable under basal
      conditions. The lipid species data were subjected to multivariate statistical
      analysis of principal components, revealing numerous specific alterations upon
      ORP silencing. The cells cultured in basal conditions or treated with LPS showed
      qualitatively different responses. However, in LPS-stimulated cells silencing of
      any of the three ORPs decreased the relative amount of arachidonic acid
      containing PI species, increased the corresponding PE species, and favored 16
      carbon sphingomyelin (SM) species at the expense of the 24-carbon ones. As a
      conclusion, the present study reveals the distinct and sophisticated roles of
      different ORP proteins as regulators of macrophage lipid composition, with
      implications for inflammatory signaling.

PMID- 22609462
TI  - Caveolae and non-caveolae lipid raft microdomains of human umbilical vein
      endothelial cells contain utrophin-associated protein complexes.
AB  - Several studies have shown the importance of dystrophin-associated protein
      complex in the development of muscular dystrophies and dilated cardiomyopathy
      associated to vascular dysfunction. In vascular endothelium, dystrophin is
      substituted for utrophin (autosomal homolog of dystrophin); however, its role in
      this tissue is unknown. Therefore, it is important to obtain a more extensive
      knowledge of utrophin and its associated proteins in endothelial cells. In a
      previous study, we demonstrated the presence of utrophin-associated protein
      complex (UAPC) in human umbilical vein endothelial cells HUVEC, which interacts
      with caveolin-1 (Cav-1) and endothelial nitric oxide synthase (eNOS). Also, some
      of our observations suggested the presence of this complex in distinct membrane
      domains. Therefore, the aim of this study was to analyze the presence of the UAPC
      in caveolae and non-caveolae lipid rafts domains of HUVEC at baseline and with a
      mechanical stimulus. It was demonstrated, by subcellular fractionation and co
      immunoprecipitation assays, the association of UAPC with Cav-1 and eNOS in
      caveolae domains, as well as its interaction with eNOS in non-caveolae lipid raft
      domains. Additionally, it was also observed that mechanical stress on endothelial
      cells induced activation and release of eNOS from both caveolae and non-caveolae
      lipid raft associated to UAPC. Together these results suggest that UAPC located
      in caveolae and non-caveolae lipid raft domains of HUVECs may have a
      mechanosensory function that could participate in the control of eNOS activity.

PMID- 22609463
TI  - Treatment with lenalidomide and dexamethasone in patients with multiple myeloma
      and renal impairment.
AB  - Renal impairment (RI) is a common complication affecting patients with multiple
      myeloma (MM). Timely identification of MM-related RI and early treatment with
      novel antimyeloma agents can reverse renal damage in a high proportion of
      patients and improve outcomes. The IMiDs(r) immunomodulatory compound
      lenalidomide (Len) in combination with dexamethasone (Dex) is an effective and
      well-tolerated regimen for patients with relapsed or refractory (RR) MM. A
      retrospective analysis of Phase III data has shown that Len/Dex remains effective
      and well-tolerated in patients with moderate or severe RI, albeit with an
      increase in myelosuppression. This analysis demonstrated that in a high
      proportion of patients Len/Dex treatment can reverse MM-related RI and restore
      normal function. Lenalidomide has a predominantly renal route of excretion and in
      patients with RI the plasma concentration and half-life of the drug are
      significantly increased. As a consequence, lower starting doses are required in
      patients with RI to avoid over-exposure and an increased risk of adverse events,
      while maintaining good therapeutic index. A prospective cohort study in 50
      patients with RRMM has reported that when Len/Dex dosing was adjusted according
      to renal function, response rates and survival outcomes were similar in patients
      with and without RI, and there was no increase in adverse events in patients with
      RI. Further clinical studies are required to confirm the efficacy and
      tolerability of Len/Dex regimens in MM patients with RI, and to evaluate the
      impact of reversing renal damage in terms of patient survival.

PMID- 22609464
TI  - Epitope characterization of pre-existing and developing antibodies to an
      aglycosylated monoclonal antibody therapeutic of G1m17,1 allotype.
AB  - Allotypes of IgG1 molecules can influence the immunogenicity of therapeutic
      monoclonal antibodies and may account for the presence of some pre-existing
      antibodies. An electrochemiluminescent (ECL) bridging immunoassay was used to
      characterize the binding epitopes of anti-therapeutic antibodies (ATAs) in a
      Phase 1 single ascending dose clinical trial of a therapeutic aglycosylated
      IgG1monoclonal antibody (mAb). There was no evidence for ATAs specific for a
      possible neo-epitope created due to the lack of glycosylation. ATAs that
      developed post-treatment were specific for the F(ab')2, whereas, pre-existing
      ATAs were specific to the Fc region. Further characterization of the pre-existing
      ATAs identified the specific epitope to be the G1m1 allotype determinant in the
      Fc of the therapeutic. A novel competitive bridging assay was developed to verify
      that serum IgG1 from subjects with pre-existing anti-G1m1 antibodies was
      homozygous for the antithetical allotype (G1m3). The endogenous G1m allotype of
      all subjects was assessed and correlation to ATA incidence and adverse events was
      evaluated. Interestingly, the pre-existing anti-allotype antibody in subjects
      persisted but was not augmented after dosing, indicating the lack of a secondary
      immune response to this epitope. These studies indicate the relationship of the
      therapeutic allotype and the corresponding allotype of subjects is an important
      component to further understand the impact of immunogenicity on the safety and
      efficacy of therapeutic antibodies.

PMID- 22609465
TI  - Peroral endoscopic myotomy (POEM) for oesophageal achalasia: preliminary results
      in humans.
AB  - BACKGROUND: Peroral endoscopic myotomy has been developed to provide a less
      invasive treatment for oesophageal achalasia compared to surgical cardiomyotomy.
      AIMS: To report our initial experience on feasibility, safety and clinical
      efficacy of peroral endoscopic myotomy. METHODS: Eleven patients (eight women,
      mean age 32, range 24-58) underwent an attempt at peroral endoscopic myotomy
      under general anaesthesia. After submucosal injection, a mucosal entry into the
      oesophageal submucosa, and a tunnel extending to the oesophagogastric junction
      and beyond into the stomach were created (total mean length: 15 +/- 1.7 cm).
      Myotomy of the circular oesophageal and gastric muscle bundles was then achieved
      under direct vision (total mean length: 10.2 +/- 2.8 cm). Haemostatic clips were
      used to close the mucosal entry. The Eckardt Score and manometry were used to
      evaluate the results. RESULTS: Peroral endoscopic myotomy could be completed in
      10 out of 11 patients (91%). Mean procedure time was 100.7 min (range 75-140
      min). No major complication occurred. Clinical success was achieved in all
      patients at 1-month follow-up (Eckardt Score 7.1 vs. 1.1, p=0). Lower oesophageal
      sphincter pressure decreased from 45.1 to 16.9 mm Hg (p=0). CONCLUSIONS: This
      initial experience with peroral endoscopic myotomy shows its safety and efficacy
      in the treatment of achalasia. Further studies are warranted to assess the long
      term efficacy and to compare peroral endoscopic myotomy with other treatment
      modalities.

PMID- 22609466
TI  - Effects of deterministic and random refuge in a prey-predator model with parasite
      infection.
AB  - Most natural ecosystem populations suffer from various infectious diseases and
      the resulting host-pathogen dynamics is dependent on host's characteristics. On
      the other hand, empirical evidences show that for most host pathogen systems, a
      part of the host population always forms a refuge. To study the role of refuge on
      the host-pathogen interaction, we study a predator-prey-pathogen model where the
      susceptible and the infected prey can undergo refugia of constant size to evade
      predator attack. The stability aspects of the model system is investigated from a
      local and global perspective. The study reveals that the refuge sizes for the
      susceptible and the infected prey are the key parameters that control possible
      predator extinction as well as species co-existence. Next we perform a global
      study of the model system using Lyapunov functions and show the existence of a
      global attractor. Finally we perform a stochastic extension of the basic model to
      study the phenomenon of random refuge arising from various intrinsic, habitat
      related and environmental factors. The stochastic model is analyzed for
      exponential mean square stability. Numerical study of the stochastic model shows
      that increasing the refuge rates has a stabilizing effect on the stochastic
      dynamics.

PMID- 22609467
TI  - Minimal output sets for identifiability.
AB  - Ordinary differential equation models in biology often contain a large number of
      parameters that must be determined from measurements by parameter estimation. For
      a parameter estimation procedure to be successful, there must be a unique set of
      parameters that can have produced the measured data. This is not the case if a
      model is not uniquely structurally identifiable with the given set of outputs
      selected as measurements. In designing an experiment for the purpose of parameter
      estimation, given a set of feasible but resource-consuming measurements, it is
      useful to know which ones must be included in order to obtain an identifiable
      system, or whether the system is unidentifiable from the feasible measurement
      set. We have developed an algorithm that, from a user-provided set of variables
      and parameters or functions of them assumed to be measurable or known, determines
      all subsets that when used as outputs give a locally structurally identifiable
      system and are such that any output set for which the system is structurally
      identifiable must contain at least one of the calculated subsets. The algorithm
      has been implemented in Mathematica and shown to be feasible and efficient. We
      have successfully applied it in the analysis of large signalling pathway models
      from the literature.

PMID- 22609468
TI  - Cytotoxicity of quinone drugs on highly proliferative human leukemia T cells:
      reactive oxygen species generation and inactive shortened SOD1 isoform
      implications.
AB  - Drugs containing the quinone group were tested on hyperproliferative leukemia T
      cells (HLTC: Jhp and Jws) and parental Jurkat cells. Doxorubicin, menadione and
      adaphostin produced different effects on these cell lines. Rapid doxorubicin
      induced cell death in Jurkat cells was mediated by caspase activation.
      Doxorubicin-induced cell death of HLTCs was delayed due to the absence of caspase
      3 and -8 expression. Delayed HLTC cell death was mediated and triggered by the
      generation of reactive oxygen species (ROS). Other drugs containing quinone
      groups, such as menadione and adaphostin, were also tested on HLTC and both were
      toxic by a caspase-independent mechanism. The toxicity of these drugs correlated
      with the generation of the superoxide anion, which increased and was more
      effective in HLTCs than in parental Jurkat cells. Accordingly, SOD1 activity was
      much lower in HLTCs than in Jurkat cells. This lower SOD1 activity in HLTCs was
      associated not only with the absence of the wild-type (16 kDa) SOD1 monomer but
      also with the presence of a shortened (14 kDa) SOD1 monomer isoform. Moreover,
      the cytotoxicity of drugs containing the quinone group was prevented by
      incubation with manganese(III) tetrakis (4-benzoic acid) porphyrin (MnTBAP), a
      cell-permeable superoxide dismutase mimetic and a potent inhibitor of oxidation.
      These findings could explain the sensitivity of HLTCs to drugs containing the
      quinone group using a mechanism dependent on oxidative stress. These observations
      can also be useful to target hyperproliferative leukemias that are resistant to
      the classical caspase-dependent apoptotic pathway.

PMID- 22609469
TI  - Glycocodon theory--the first table of glycocodons.
AB  - Hydrophobic cellular membranes separate cells from an environment that is
      generally based on water. Therefore, it is not surprising that hydrophilic
      glycans and glycoproteins are exposed on the lipidic surface of membranes and
      that the glycocalyx has evolved in all basic cell types. During the evolution of
      multicellular life, the surface exposed protein-glycan interactions were taken as
      the origin of the language of cell-cell communication. The bioinformatics
      analysis presented here reveals that the amino acid triplets, the glycocodons,
      can be deduced for each glycan letter (monosaccharide). This theory proposes to
      distinguish between the "sugar code" (the sugar sequence) and the "glycocode"
      (evolutionary selected amino acids recognising the mono-sugar). Similarly to
      genetic code, original glycocodons are related to G, A, V, and D amino acids.
      Modern glycocodons can be deduced from GAVD-glycocodons using hydropathic
      similarity. In general, the amino acid triplets can be assembled from one
      dipeptide that is specific to a monosaccharide plus a polar amino acid. This
      theory may shed a different light on the reason for WWD conservation in the
      active sites of oligosaccharyltransferases and for GGQ in the active sites of
      ribosomes.

PMID- 22609470
TI  - Cooperation, behavioural synchrony and status in social networks.
AB  - In this paper we present a new approach to modelling group coordination, based on
      dyadic synchronisation in a non-panmictic, structured network (a problem that
      applies widely to all species that live in medium to large groups). Using this
      approach, we present three models with three new theoretical results. (1) Multi
      layered networks are optimal for groups that face costs associated with
      maintaining relationships among the members, combined with costs associated with
      information flows. (2) The presence of a social hierarchy can be an adaptive
      feature of the community: the steeper the optimal social hierarchy is, the fewer
      relationships group members need to have. (3) Falling communication costs lead to
      a less steep optimal social hierarchy in communities in which socially useful
      information is evenly distributed, but to an even steeper social hierarchy in
      groups in which socially useful information is uneven. Thus we show how, when
      communication is costly, cooperation can give rise to communities that are
      socially highly structured.

PMID- 22609471
TI  - Persistence of anxiety disorders and concomitant changes in cortisol.
AB  - In a clinical sample of 116 children and adolescents we studied the relation
      between the course of an anxiety disorder during treatment and the concomitant
      changes in cortisol levels. Assessments at baseline, after three months, and at
      one-year follow-up were performed with the Anxiety Disorders Interview Schedule.
      When we compared cortisol levels at baseline and one-year follow-up, persistence
      of the anxiety disorder was associated with both increased daytime cortisol
      production (F=3.2, p=0.04) and a trend towards a decreased cortisol morning rise
      (F=2.4, p=0.09). At one-year follow-up daytime cortisol production was lowest in
      the early remitters (109.7+/-29.2 h mmol/l), higher in the late remitters
      (121.0+/-40.0 h mmol/l) and highest in the non-remitters (131.1+/-48.9 h mmol/l).
      Early remitters had the highest cortisol morning rise (1.1+/-1.5 h mmol/l),
      followed by the late remitters (0.8+/-1.8 h mmol/l), the non-remitters had the
      lowest cortisol morning rise (0.07+/-1.7 h mmol/l). Persistence of an anxiety
      disorder may thus lead to changes in HPA-axis functioning, underscoring the
      importance adequate treatment of anxiety disorders.

PMID- 22609472
TI  - Spontaneous behavioral rhythms in the isolated CNS of insects - presenting new
      model systems.
AB  - Three new model systems for the study of rhythm generation in the isolated insect
      central nervous system are presented. Natural behavioral rhythms are produced in
      these cases spontaneously in the isolated CNS. They can be monitored as output of
      motoneurons at peripheral nerves. Recording from the neurons of the pattern
      generating networks during this output gives insight into neural control
      principles of locust respiration, of hemolymph pumping in accessory pumping
      organs of crickets, and of crawling movements in larvae of the weevil
      Rhynchophorus ferrugineus.

PMID- 22609473
TI  - Tumor regulation of myeloid-derived suppressor cell proliferation and
      trafficking.
AB  - A stress response can induce myeloid progenitor cell (MPC) proliferation,
      mobilization, and extramedullary hematopoiesis (EMH) within lymphoid and
      parenchymal organs. Our studies using in vivo BrdU labeling, Ki-67 IHC staining,
      and carboxyfluorescein succinimidyl ester (CFSE) adoptive cell transfer revealed
      that spleens, rather than bone marrow (BM) and peripheral blood (PB), from 4T1
      mammary tumor-bearing (TB) mice were the primary site of MPC proliferation. The
      resultant increase in MPCs was associated with tumor hematopoietic growth factor
      (GF) transcription, decreased apoptosis, as well as, prolonged survival of
      splenic MPCs. In naive mice, i.v. injected CFSE-labeled MDSCs (myeloid-derived
      suppressor cells) initially accumulated in the lungs, while in TB mice, they
      rapidly sequestered in the spleen. In contrast, a few of the injected MDSCs and
      leukocytes arrested, proliferated, or accumulated in the marrow, tumor, or PB of
      TB mice. However, BrdU labeling revealed a significant demargination of
      proliferating splenic MPCs into the PB. In tumors, despite high GF transcript
      levels, we found that a high frequency of MDSCs was apoptotic. In summary, tumor
      growth and cytokines regulate MPC proliferation, trafficking, accumulation,
      apoptosis, and survival.

PMID- 22609474
TI  - Possible impact of ADRB3 Trp64Arg polymorphism on BMI in patients with
      schizophrenia.
AB  - BACKGROUND: The beta3-adrenoceptor (ADRB3) gene Trp64Arg polymorphism has been
      shown to be associated with obesity as well as type 2 diabetes and cardiovascular
      disease. The incidence of overweight and the risks of type 2 diabetes and
      cardiovascular disease are also increased in major depression and schizophrenia.
      We hypothesized that the Trp64Arg polymorphism may be associated with increased
      risk of schizophrenia and depression. METHODS: The Trp64Arg was genotyped in 504
      patients with schizophrenia, 650 with major depressive disorder (MDD), and 1170
      healthy controls. Of these participants, body mass index (BMI) data were
      available for 125 patients with schizophrenia, 219 with MDD, and 261 controls.
      RESULTS: No significant difference in genotype or allele distribution was found
      across the diagnostic groups. No significant difference in BMI was observed
      between the Arg allele carriers and the non-carriers in the MDD and the control
      groups. However, patients with schizophrenia carrying the Arg allele had
      significantly higher BMI (Mean (SD): Arg carriers: 26.5 (6.9), Arg non-carriers:
      23.8 (4.3); P=0.019) and a higher rate of being overweight (BMI of 25 or more)
      compared to their counterparts (Trp/Trp group) (% overweight (SE): Arg carriers:
      52.3 (7.5), Arg non-carriers: 32.1 (5.2); P=0.027). CONCLUSIONS: We obtained no
      evidence for the association of ADRB3 Trp64Arg with the development of MDD or
      schizophrenia. However, the Arg allele was found to be associated with higher BMI
      and being overweight in patients with schizophrenia. This may imply that
      genotyping ADRB3 is of clinical use to detect schizophrenic individuals at risk
      for developing obesity.

PMID- 22609475
TI  - Introduction, availability and role of simulation in surgical education and
      training: review of current evidence and recommendations from the Association of
      Surgeons in Training.
AB  - The utility of simulation in surgical training is now well-established, with
      proven validity and demonstrable transfer of skills to the clinical setting.
      Through a reduction in the technical learning curve, simulation can prepare
      surgeons for actual practice and in doing so it has the potential to improve both
      patient safety and service efficiency. More broadly, multi-disciplinary
      simulation of the theatre environment can aid development of non-technical skills
      and assist in preparing theatre teams for infrequently encountered scenarios such
      as surgical emergencies. The role of simulation in the formal training curriculum
      is less well-established, and availability of facilities for this is currently
      unknown. This paper reviews the contemporary evidence supporting simulation in
      surgical training and reports trainee access to such capabilities. Our national
      surgical trainee survey with 1130 complete responses indicated only 41.2% had
      access to skills simulator facilities. Of those with access, 16.3% had
      availability out-of-hours and only 54.0% had local access (i.e. current work
      place). These results highlight the paucity in current provision of surgical
      skills simulator facilities, and availability (or awareness of availability)
      varies widely between region, grade and specialty. Based on these findings and
      current best-evidence, the Association of Surgeons in Training propose 22 action
      points for the introduction, availability and role of simulation in surgical
      training. Adoption of these should guide trainers, trainees and training bodies
      alike to ensure equitable provision of appropriate equipment, time and resources
      to allow the full integration of simulation into the surgical curriculum.

PMID- 22609476
TI  - Changed phagocytic activity and pattern of Fcgamma and complement receptors on
      blood monocytes in sarcoidosis.
AB  - We have recently revealed that mycobacterial heat shock proteins (Mtb-hsp),
      involved in forming of immune complexes (CIs), can induce immune response in
      sarcoidosis (SA). The complexemia may result from inappropriate phagocytosis and
      clearance of CIs by monocytes with following persistent antigenemia and granuloma
      formation. Because an aberrant expression of receptors for Fc fragment of
      immunoglobulin G (FcgammaR) and complement receptors (CR) on monocytes can be
      involved in this process, we have evaluated the expression of FcgammaRI (CD64),
      FcgammaRII (CD32), FcgammaRIII (CD16) and CR1 (CD35), CR3 (CD11b), CR4 (CD11c)
      receptors on blood CD14(+) monocytes and its phagocytic activity in 24 patients
      with SA and 20 healthy volunteers using flow cytometry. We found significantly
      increased expression of all examined FcgammaR and decreased expression of CD35
      and CD11c on CD14(+) monocytes in SA patients vs controls. Significantly
      increased percentage of CD14(+)CD16(+)CD35(-), CD14(+)CD64(+)CD35(+),
      CD14(+)CD64(+)CD11b(+), CD14(+)CD64(+)CD11c(+) and decreased of CD14(+)CD32(
      )CD35(+), CD14(+)CD32(-)CD11b(+), CD14(+)CD32(-)CD11c(+) monocytes' phenotypes
      was revealed in SA. The total number and percentage of phagocyting monocytes was
      significantly increased in SA as compared with controls. In conclusion, altered
      expression of FcgammaR and CR on CD14(+) monocytes and its increased phagocytic
      activity may be responsible for high antigen load, persistent antigenemia and
      immunocomplexemia in SA patients.

PMID- 22609477
TI  - The intercellular adhesion molecule-1 (ICAM-1) gene polymorphism K469E in end
      stage renal disease patients with cardiovascular disease.
AB  - The intercellular adhesion molecule-1 (ICAM-1) mediates interaction of activated
      endothelial cells with leukocytes. It plays an important role in the pathogenesis
      of atherosclerosis. A functionally important polymorphism of the ICAM-1 gene,
      K469E, has been described. We investigated whether this polymorphism influences
      the risk of CVD in end-stage renal disease (ESRD) patients. The groups of 1016
      ESRD patients and 824 healthy individuals were genotyped by PCR and allele
      specific oligonucleotide technique. The T allele of the K469E polymorphism was
      significantly more frequent in ESRD CVD+ patients than CVD- and controls (OR
      2.26, 95% CI 1.87-2.72 and 1.82, 95% CI 1.55-2.11, respectively). The TT genotype
      was also more frequent in CVD+ patients (OR 9.90, 95% CI 6.17-15.88 vs. CVD-
      subgroup). When patients were stratified according to clinical outcome of CVD,
      there was a tendency towards higher frequencies of the T allele and TT genotype
      in patients with myocardial infarction (OR for T allele 1, 57, 95% CI 1.12-2.18
      vs. patients without MI). In the multivariate regression analysis the carrier
      status of T allele of K469E was an independent risk factor of susceptibility to
      CVD. Our data suggest that the ICAM-1 K469E polymorphism is associated with CVD
      in ESRD patients.

PMID- 22609478
TI  - Identification of signalling pathways triggered by changes in the mechanical
      environment in rat chondrocytes.
AB  - AIM: The aim of this work was to determine the pathways implicated in the
      mechanosensing of chondrocytes. METHODS: Rat chondrocytes were cultured in
      collagen hydrogels of different stiffness (2-20 Pa) in normoxia and hypoxia, in
      monolayer and embedded inside hydrogels. First, chondrocyte were cultured on
      hydrogels in the presence of antibodies to block integrins. Second, custom RT-PCR
      array plates and western blot were used to detect changes in expression of genes
      implicated in downstream signalling pathways. RESULTS: The results allowed us to
      demonstrate the mechanosensing of chondrocytes for changes in stiffness in the
      range of Pascals. We also identified Non-Muscle Myosin II (NMMII) and integrins
      alpha1, beta1 and beta3 as participants in the mechanosensing, since their
      blockade inhibits the sensing of the stiffness, and they are up-regulated in the
      process. RT-PCR arrays and western blot detected up-regulation of Paxillin, RhoA,
      Fos, Jun and Sox9. We detected no expression of Src in the monolayer cultures,
      but we found a role for this protein in 3D. The expression of HIF-1alpha was not
      modified under normoxia but was found to participate under hypoxia. Focal
      Adhesion Kinase (FAK), showed a direct relationship with the expression of
      Aggrecan in hypoxia and an inverse one in normoxia. Finally, immunofluorescence
      analysis located the expression of factors AP-1, Sox-9 and HIF-1alpha inside the
      cell nuclei and RhoA, Src, Paxillin and FAK close to the cytoplasmic membrane.
      CONCLUSIONS: We determined here some of the genes that are up-regulated during
      the process of chondrocyte mechanosensing.

PMID- 22609480
TI  - A novel polydnaviral gene family, BEN, and its immunosuppressive function in
      larvae of Plutella xylostella parasitized by Cotesia plutellae.
AB  - A full genome sequence of the episomal form of Cotesia plutellae bracovirus
      (CpBV) suggests 11 BEN family genes. This study analyzed their expression and
      physiological function in the viral host, Plutella xylostella. All 11 BEN family
      genes were expressed during entire parasitization period of P. xylostella larvae.
      In addition, these BEN family genes were expressed in fat body, gut, epidermis,
      and hemocytes in final larval instar of parasitized P. xylostella. The 11 BEN
      family genes were transiently expressed in nonparasitized larvae by injection of
      each viral segment containing its corresponding BEN family gene. The transient
      expression of BEN family genes significantly suppressed hemocyte nodule formation
      in response to bacterial challenge. Subsequent injection of double-stranded RNA
      specific to each BEN family gene suppressed the expression of the BEN family gene
      and rescued the immunosuppression. These results indicate that 11 BEN family
      genes are expressed in larvae parasitized by C. plutellae and play crucial role
      in inducing immunosuppression. Homologous BEN family genes were found in other
      bracoviral genomes. We propose BEN domain-containing genes as a new functional
      gene family in polydnaviruses.

PMID- 22609479
TI  - Initial application of EPIC-MUCT to assess mouse articular cartilage morphology
      and composition: effects of aging and treadmill running.
AB  - OBJECTIVE: The current study was undertaken to adapt Equilibrium Partitioning of
      an Ionic Contrast agent via microcomputed tomography (EPIC-MUCT) to mouse
      articular cartilage (AC), which presents a particular challenge because it is
      thin (30 MUm) and has a small volume (0.2-0.4 mm(3)), meaning there is only
      approximately 2-4 MUg of chondroitin sulfate (CS) glycosaminoglycan per joint
      surface cartilage. DESIGN: Using 6 MUm isotropic voxels and the negatively
      charged contrast agent ioxaglate (Hexabrix), we optimized contrast agent
      concentration and incubation time, assessed two methods of tissue preservation
      (formalin fixation and freezing), examined the effect of ex vivo chondroitinase
      ABC digestion on X-ray attenuation, assessed accuracy and precision, compared
      young and skeletally mature cartilage, and determined patterns of degradation in
      a murine cartilage damage model induced by treadmill running. RESULTS: The
      optimal concentration of the contrast agent was 15%, formalin fixation was
      preferred to freezing, and 2 h of incubation was needed to reach contrast agent
      equilibrium with formalin-fixed specimens. There was good agreement with
      histologic measurements of cartilage thickness, although MUCT over-estimated
      thickness by 13% (5 MUm) in 6-week-old mice. Enzymatic release of 0.8 MUg of
      chondrotin sulfate (about 40% of the total) increased X-ray attenuation by 17%.
      There was a 15% increase in X-ray attenuation in 14-week-old mice compared to 6
      week-old mice (P < 0.001) and this corresponded to 65% decrease in CS content at
      14 weeks. The older mice also had reductions of 33% in cartilage thickness and
      44% in cartilage volume (P < 0.001). Treadmill running induced a 16% decrease in
      cartilage thickness (P = 0.012) and a 12% increase in X-ray attenuation (P =
      0.006) in 14-week-old mice. CONCLUSION: This technique enables non-destructive
      visualization and quantification of murine femoral AC in three dimensions with
      anatomic specificity and should prove to be a useful new tool in studying
      degeneration of cartilage in mouse models.

PMID- 22609481
TI  - Frizzled-3a and slit2 genetically interact to modulate midline axon crossing in
      the telencephalon.
AB  - The anterior commissure forms the first axon connections between the two sides of
      the embryonic telencephalon. We investigated the role of the transmembrane
      receptor Frizzled-3a in the development of this commissure using zebrafish as an
      experimental model. Knock down of Frizzled-3a resulted in complete loss of the
      anterior commissure. This defect was accompanied by a loss of the glial bridge,
      expansion of the slit2 expression domain and perturbation of the midline
      telencephalic-diencephalic boundary. Blocking Slit2 activity following knock down
      of Frizzled-3a effectively rescued the anterior commissure defect which suggested
      that Frizzled-3a was indirectly controlling the growth of axons across the
      rostral midline. We have shown here that Frizzled-3a is essential for normal
      development of the commissural plate and that loss-of-function causes Slit2
      dependent defects in axon midline crossing in the embryonic vertebrate forebrain.
      These data supports a model whereby Wnt signaling through Frizzled-3a attenuates
      expression of Slit2 in the rostral midline of the forebrain. The absence of Slit2
      facilitates the formation of a midline bridge of glial cells which is used as a
      substrate for commissural axons. In the absence of this platform of glia,
      commissural axons fail to cross the rostral midline of the forebrain.

PMID- 22609482
TI  - The effects of different pre-game motivational interventions on athlete free
      hormonal state and subsequent performance in professional rugby union matches.
AB  - We examined the effect of different pre-match motivational interventions on
      athlete free testosterone (T) and cortisol (C) concentrations and subsequent
      match performance in professional rugby union. Male participants (n=12) playing
      at a senior or academy level in rugby union were recruited and each completed
      three interventions (15 min each) before a competitive game; 1) watching a video
      clip of successful skill execution by the player with positive coach feedback
      [VPCF1]; 2) watching a video clip of successful skill execution by an opposing
      player with cautionary coach feedback [VCCF], 3) the player left alone to self
      motivate [SM1]. The first and last interventions were retested [VPCF2 and SM2].
      Salivary free T and C measures were taken pre-intervention and pre-game. Within
      each game, players were rated by coaching staff on a key performance indicator
      (KPI) from identified skills and an overall performance indicator (OPI), where 1
      = best performance to 5 = worst performance. The VPCF1 and VPCF2 interventions
      both promoted significant T responses (11.8% to 12.5%) before each game and more
      so than SM1, SM2 and VCCF. The VCCF approach produced the largest C response
      (17.6%) and this differed from all other treatments. The VPCF interventions were
      also associated with better game KPI (1.5 to 1.8) and OPI ratings (1.7 to 1.8)
      than SM1, SM2 and/or VCCF. Across all treatments, greater individual T responses
      and lower C responses were associated with better KPI and OPI outcomes. In
      conclusion, the pre-game presentation of motivational strategies to athletes
      involving specific video footage and coach feedback produced different outcomes
      on two indicators of match performance, which were also associated with changes
      in free hormonal state.

PMID- 22609484
TI  - New scenarios for neuronal structural plasticity in non-neurogenic brain
      parenchyma: the case of cortical layer II immature neurons.
AB  - The mammalian central nervous system, due to its interaction with the
      environment, must be endowed with plasticity. Conversely, the nervous tissue must
      be substantially static to ensure connectional invariability. Structural
      plasticity can be viewed as a compromise between these requirements. In adult
      mammals, brain structural plasticity is strongly reduced with respect to other
      animal groups in the phylogenetic tree. It persists under different forms, which
      mainly consist of remodeling of neuronal shape and connectivity, and, to a lesser
      extent, the production of new neurons. Adult neurogenesis is mainly restricted
      within two neurogenic niches, yet some gliogenic and neurogenic processes also
      occur in the so-called non-neurogenic tissue, starting from parenchymal
      progenitors. In this review we focus on a population of immature, non-newly
      generated neurons in layer II of the cerebral cortex, which were previously
      thought to be newly generated since they heavily express the polysialylated form
      of the neural cell adhesion molecule and doublecortin. These unusual neurons
      exhibit characteristics defining an additional type of structural plasticity,
      different from either synaptic plasticity or adult neurogenesis. Evidences
      concerning their morphology, antigenic features, ultrastructure, phenotype,
      origin, fate, and reaction to different kind of stimulations are gathered and
      analyzed. Their possible role is discussed in the context of an enriched
      complexity and heterogeneity of mammalian brain structural plasticity.

PMID- 22609485
TI  - Stopping tamoxifen peri-operatively for VTE risk reduction: a proposed management
      algorithm.
AB  - Tamoxifen is a selective oestrogen receptor modulator used in pre-menopausal
      oestrogen receptor positive breast cancer patients as adjuvant endocrine
      treatment. Increased risk of venous thrombo-embolism with the use of Tamoxifen is
      well known from published literature. This risk further increases in patients
      undergoing surgical procedures of high risk involving prolonged period of
      immobilization, therefore withholding Tamoxifen treatment in the immediate peri
      operative period should be considered as a risk reducing measure. In the absence
      of nationally agreed guidelines on the safe duration for stoppage of treatment in
      the pre and post operative period without worsening cancer prognosis, operating
      surgeons and individual trusts have adopted their own guidelines based on
      individual experience. From the available evidence in the literature on the VTE
      risk assessments based on age, operative procedure and pharmacokinetics of the
      Tamoxifen drug we would like to propose a working algorithm for selecting the
      right patient group and safe treatment stoppage durations. These proposed
      guidelines are formulated taking all the risk factors of VTE, operative risks,
      pharmacokinetics of the drug and chemotherapy risks into consideration. With this
      guidance, we aim to help surgeons across different specialities in the decision
      making process through a structured evidence based approach.

PMID- 22609487
TI  - Interleukin 6 and C-reactive protein in esophageal cancer.
AB  - Esophageal cancer (EC) is one of the most aggressive malignant tumors of the
      gastrointestinal tract. It is well known that cancer initiation and tumor
      development are closely linked with inflammation. C-reactive protein (CRP) and
      interleukin-6 (IL-6) are acute-phase proteins involved in cancer development. It
      was suggested that CRP and IL-6 play potential roles in the growth and
      progression of malignant tumors, including EC. The aim of the study was to
      describe the significance of IL-6 and CRP in the development of esophageal cancer
      and to assess the potential role of their serum levels as prognostic indicators
      of EC patient's survival.

PMID- 22609488
TI  - Progress in high-throughput assays of MGMT and APE1 activities in cell extracts.
AB  - DNA repair activity is of interest as a potential biomarker of individual
      susceptibility to genotoxic agents. In view of the current trend for exploitation
      of large cohorts in molecular epidemiology projects, there is a pressing need for
      the development of phenotypic DNA repair assays that are high-throughput, very
      sensitive, inexpensive and reliable. Towards this goal we have developed and
      validated two phenotypic assays for the measurement of two DNA repair enzymes in
      cell extracts: (1) O(6)-methylguanine-DNA-methyltransferase (MGMT), which repairs
      the O(6)-alkylguanine-type of adducts induced in DNA by alkylating genotoxins;
      and (2) apurinic/apyrimidinic endonuclease 1 (APE 1), which participates in base
      excision repair (BER) by causing a rate-limiting DNA strand cleavage 5' to the
      abasic sites. The MGMT assay makes use of the fact that: (a) the enzyme works by
      irreversibly transferring the alkyl group from the O(6) position of guanine to a
      cystein residue in its active site and thereby becomes inactivated and (b) that
      the free base O(6)-benzylguanine (BG) is a very good substrate for MGMT. In the
      new assay, cell extracts are incubated with BG tagged with biotin and the
      resulting MGMT-BG-biotin complex is immobilized on anti-MGMT-coated microtiter
      plates, followed by quantitation using streptavidin-conjugated alkaline
      phosphatase and a chemiluminescence-producing substrate. A one-step/one-tube
      phenotypic assay for APE1 activity has been developed based on the use of a
      fluorescent molecular beacon (partially self-complementary oligonucleotide with a
      hairpin-loop structure carrying a fluorophore and a quencher at each end). It
      also contains a single tetrahydrofuran residue (THF) which is recognized and
      cleaved by APE1, and the subsequently formed single-stranded oligomer becomes a
      fluorescence signal emitter. Both assays are highly sensitive, require very small
      amounts of protein extracts, are relatively inexpensive and can be easily
      automated. They have been extensively validated and are being used in the context
      of large-scale molecular epidemiology studies.

PMID- 22609483
TI  - How mechanisms of perceptual decision-making affect the psychometric function.
AB  - Psychometric functions are often interpreted in the context of Signal Detection
      Theory, which emphasizes a distinction between sensory processing and non-sensory
      decision rules in the brain. This framework has helped to relate perceptual
      sensitivity to the "neurometric" sensitivity of sensory-driven neural activity.
      However, perceptual sensitivity, as interpreted via Signal Detection Theory, is
      based on not just how the brain represents relevant sensory information, but also
      how that information is read out to form the decision variable to which the
      decision rule is applied. Here we discuss recent advances in our understanding of
      this readout process and describe its effects on the psychometric function. In
      particular, we show that particular aspects of the readout process can have
      specific, identifiable effects on the threshold, slope, upper asymptote, time
      dependence, and choice dependence of psychometric functions. To illustrate these
      points, we emphasize studies of perceptual learning that have identified changes
      in the readout process that can lead to changes in these aspects of the
      psychometric function. We also discuss methods that have been used to distinguish
      contributions of the sensory representation versus its readout to psychophysical
      performance.

PMID- 22609490
TI  - Safety evaluation of Evesse EPC, an apple polyphenol extract rich in flavan-3
      ols.
AB  - The safety of the apple polyphenol extract EvesseEPC, which is rich in flavan-3
      ols, particularly epicatechin, was evaluated. Both in a bacterial reverse
      mutation test and a mouse lymphoma assay, EvesseEPC showed a positive response in
      vitro. In vivo studies (UDS test in hepatocytes, bone marrow micronucleus test
      and comet assay in intestinal cells) were all negative and hence Evesse EPC is
      considered not to have genotoxic properties in vivo. In a 90-day study in rats,
      EvesseEPC was administered at dietary levels of 0%, 1.25%, 2% and 3.25%. Body
      weights were decreased in the high-dose group in both sexes without effects on
      feed or water intake. In the high-dose group, thrombocytes (males) and creatinine
      (both sexes) were decreased, prothrombin time (males) was increased, and liver,
      kidneys and spleen weights were increased (males), without histological
      correlates. Diffuse acinar cell hypertrophy, observed in the parotid salivary
      glands in all treatment groups, was not considered as adverse and presumably
      reflected a local, reversible and adaptive response to direct contact with
      EvesseEPC. The NOAEL for EvesseEPC in rats was 2% in the diet, equivalent to an
      overall average intake of 1.3 and 1.5 g/kg body weight/day for males and females,
      respectively.

PMID- 22609489
TI  - Kv1.1 knock-in ataxic mice exhibit spontaneous myokymic activity exacerbated by
      fatigue, ischemia and low temperature.
AB  - Episodic ataxia type 1 (EA1) is an autosomal dominant neurological disorder
      characterized by myokymia and attacks of ataxic gait often precipitated by
      stress. Several genetic mutations have been identified in the Shaker-like K(+)
      channel Kv1.1 (KCNA1) of EA1 individuals, including V408A, which result in
      remarkable channel dysfunction. By inserting the heterozygous V408A, mutation in
      one Kv1.1 allele, a mouse model of EA1 has been generated (Kv1.1(V408A/+)). Here,
      we investigated the neuromuscular transmission of Kv1.1(V408A/+) ataxic mice and
      their susceptibility to physiologically relevant stressors. By using in vivo
      preparations of lateral gastrocnemius (LG) nerve-muscle from Kv1.1(+/+) and
      Kv1.1(V408A/+) mice, we show that the mutant animals exhibit spontaneous myokymic
      discharges consisting of repeated singlets, duplets or multiplets, despite motor
      nerve axotomy. Two-photon laser scanning microscopy from the motor nerve, ex
      vivo, revealed spontaneous Ca(2+) signals that occurred abnormally only in
      preparations dissected from Kv1.1(V408A/+) mice. Spontaneous bursting activity,
      as well as that evoked by sciatic nerve stimulation, was exacerbated by muscle
      fatigue, ischemia and low temperatures. These stressors also increased the
      amplitude of compound muscle action potential. Such abnormal neuromuscular
      transmission did not alter fiber type composition, neuromuscular junction and
      vascularization of LG muscle, analyzed by light and electron microscopy. Taken
      together these findings provide direct evidence that identifies the motor nerve
      as an important generator of myokymic activity, that dysfunction of Kv1.1
      channels alters Ca(2+) homeostasis in motor axons, and also strongly suggest that
      muscle fatigue contributes more than PNS fatigue to exacerbate the
      myokymia/neuromyotonia phenotype. More broadly, this study points out that
      juxtaparanodal K(+) channels composed of Kv1.1 subunits exert an important role
      in dampening the excitability of motor nerve axons during fatigue or ischemic
      insult.

PMID- 22609491
TI  - Inhibitory effect of Psidium guajava water extract in the development of 2,4
      dinitrochlorobenzene-induced atopic dermatitis in NC/Nga mice.
AB  - Atopic dermatitis (AD) is a chronic, relapsing, and inflammatory skin disease
      associated with eczematous symptoms and IgE hyperproduction. Psidium guajava is
      an important food crop and medicinal plant with anti-oxidant, anti-inflammatory,
      and anti-allergic activities, supporting its traditional uses. Our previous
      studies have shown that P. guajava extract inhibits Th2 chemokine expression by
      suppressing the activation of NF-kappaB and STAT1 co-stimulated with TNF-alpha
      and INF-gamma. In this study, we investigated the inhibitory effect of P. guajava
      water extract (PGW) on 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin
      lesions in NC/Nga mice. Treatment of cream containing PGW onto DNCB-induced AD
      like skin lesions in NC/Nga mice ameliorated lesion intensity scores, levels of
      IgE, thymus and activation-regulated chemokine (TARC), TNF-alpha, and IL-4 in
      serum and ears. In contrast, PGW increased level of the immunosuppressive
      cytokine IL-10. Histological analyses demonstrated decreased thickening of the
      epidermis/dermis as well as dermal infiltration by inflammatory cells. These
      results suggest that cream containing PGW may be a potential therapeutic modality
      for AD and adjunctive agent to control pruritus in AD.

PMID- 22609492
TI  - Osteopontin is involved in estrogen-mediated protection against
      diethylnitrosamine-induced liver injury in mice.
AB  - Diethylnitrosamine (DEN) is a potent hepatotoxin and hepatocarcinogen in animals
      and possible in humans. Estrogen has been reported to play a protective role
      against DEN exposure. Osteopontin (OPN), a downstream molecular of estrogen,
      plays a role in many pathophysiological processes. In this study, we evaluate the
      role of OPN in estrogen-mediated hepatoprotection in DEN-treated mice. DEN was
      administrated intraperitoneally to C57BL/6 and OPN(-/-) mice. Compared to male
      mice, female mice exhibited significantly higher hepatic OPN expression with less
      liver damage 48 h after DEN treatment. Interestingly, enhanced OPN expression was
      predominantly detected in hepatocytes after DEN treatment. OPN deficiency
      enhanced the susceptibility to DEN, which was more apparent in females than
      males. Estrogen-mediated protection against DEN in males was abrogated by OPN
      deficiency. The protective activities of estrogen could be mimicked by exogenous
      OPN. Consistent with liver injury, oxidative stress in liver was enhanced with
      OPN depletion. OPN reduced DEN-induced oxidative stress likely through inhibition
      of CYP2A5 expression. In conclusion, we demonstrate that OPN may be involved in
      estrogen-mediated hepatoprotection in DEN-induced liver injury through
      enhancement of hepatocyte survival and inhibition of DEN biotransformation. Our
      findings may provide new insight into gender differences in chemical-induced
      liver injury and related diseases.

PMID- 22609494
TI  - Endogenous sex steroids and cardio- and cerebro-vascular disease in the
      postmenopausal period.
AB  - OBJECTIVE: Cardio- and cerebro-vascular diseases are two leading causes of death
      and long-term disability in postmenopausal women. The acute fall of estrogen in
      menopause is associated with increased cardiovascular risk. The relative
      contribution of androgen to this risk is also being recognized. The use of more
      sensitive assays for estradiol measurement and the study of receptor and carrier
      protein gene polymorphisms have provided some new information on the clinical
      relevance of endogenous sex steroids. We provide an update on the role of
      endogenous sex steroids on cardio- and cerebro-vascular disease in the
      postmenopausal period. DESIGN AND METHODS: We performed a PubMed search using the
      terms 'endogenous estrogen', 'androgen', 'cardiovascular disease', 'cerebro
      vascular disease', 'stroke', 'carotid artery disease', and 'subclinical
      atherosclerosis'. RESULTS: The majority of studies show a beneficial effect of
      endogenous estrogen on the vasculature; however, there are a few studies
      reporting the contrary. A significant body of literature has reported
      associations of endogenous estrogen and androgen with early markers of
      atherosclerosis and metabolic parameters. Data on the relevance of endogenous sex
      steroids in heart disease and stroke are inconclusive. CONCLUSIONS: Most studies
      support a beneficial role of endogenous estrogens and, probably, an adverse
      effect of androgens in the vasculature in postmenopausal women. However, the
      described associations may not always be considered as causal. It is possible
      that circulating estrogen might represent a marker of general health status or
      alternatively reflect the sum of endogenous androgens aromatized in the
      periphery. Elucidating the role of sex steroids in cardio- and cerebro-vascular
      disease remains an interesting field of future research.

PMID- 22609493
TI  - Protection of L-methionine against H2O2-induced oxidative damage in mitochondria.
AB  - Reactive oxygen species (ROS) is reported to be a critical pathogenic factor and
      mitochondria is one of the susceptible subcellular organs for oxidative damage.
      Methionine sulfoxide reductase A (MsrA) is a key anti-oxidant enzyme associated
      with cytoprotection and previous reports have revealed its importance in
      mitochondrial function. The anti-oxidation of MsrA is due to Met-centered redox
      cycle, suggesting that Met-centered redox cycle may play a critical role in
      mitochondrial protection. L-Methionine (L-Met), a natural amino acid with anti
      oxidation activity, can mimic the effect of Met-centered redox cycle. Here, we
      investigated the protection of L-Met on H(2)O(2)-induced oxidative damage in
      mitochondria. Our study demonstrated that L-Met protected H(2)O(2)-induced injury
      in CHO cells. Cytoprotections of L-Met at low concentrations (1-5mM) were
      abolished by dimethyl sulfoxide (DMSO), a competitive inhibitor of MsrA function,
      suggesting that these effects may involve the participation of MsrA.
      Overexpression of MsrA in CHO cells protected mitochondria from H(2)O(2)-induced
      downtrend of membrane potential and production of mitochondrial superoxide. Pre
      treatment with L-Met (1mM) produced a similar effect on the mitochondrial
      protection against H(2)O(2). Furthermore, it was observed that topical
      application of L-Met can prevent 12-O-tetradecanoyl-phorbol-13-acetate (TPA)
      induced oxidative damage in the skin of mice. These results suggest that anti
      oxidation activity of L-Met may promise a new strategy for the prevention of
      oxidative stress-induced damage.

PMID- 22609495
TI  - Morphogenesis as a macroscopic self-organizing process.
AB  - We start from reviewing different epistemological constructions used for
      explaining morphogenesis. Among them, we explore the explanatory power of a law
      centered approach which includes top-down causation and the basic concepts of a
      self-organization theory. Within such a framework, we discuss the
      morphomechanical models based upon the presumption of feedbacks between
      mechanical stresses imposed onto a given embryo part from outside and those
      generated within the latter as a kind of active response. A number of elementary
      morphogenetic events demonstrating that these feedbacks are directed towards
      hyper-restoration (restoration with an overshoot) of the initial state of
      mechanical stresses are described. Moreover, we show that these reactions are
      bound together into the larger scale feedbacks. That permits to suggest a
      reconstruction of morphogenetic successions in early Metazoan development
      concentrated around two main archetypes distinguished by the blastopores
      geometry. The perspectives of applying the same approach to cell differentiation
      are outlined. By discussing the problem of positional information we suggest that
      the developmental pathway of a given embryo part depends upon its preceded
      deformations and the corresponding mechanical stresses rather than upon its
      static position at any moment of development.

PMID- 22609496
TI  - Is HIV infection associated with an increased risk for cholera? Insights from a
      mathematical model.
AB  - Cholera, a waterborne gastroenteric infection, remains a significant threat to
      public health in sub-Saharan Africa, the region most heavily affected by HIV. It
      is biologically plausible that immune suppression caused by HIV infection
      predisposes to cholera. In this paper, a simple mathematical model is developed
      and comprehensively analyzed to assess whether HIV infection is associated with
      an increased risk for cholera or not. Analytical results of the model show that
      the quantities R(c) and R(h), which represents the reproductive number for
      cholera and HIV infection, respectively, provide threshold conditions that
      determine cumulative new single and dual infection cases. These threshold
      conditions can be used to gain important insights on the epidemiological
      consequences of HIV and cholera coexistence in the community. Numerical results
      are provided to support the analytical findings. The findings suggest that in a
      cholera-endemic area, HIV infection is associated with an increased risk for
      cholera.

PMID- 22609497
TI  - Exchange and correlation effects on density excitation spectra of metallic
      quantum wires at finite temperature.
AB  - We have studied the effect of exchange and correlations on the density excitation
      spectra of metallic quantum wires at finite temperature. The correlations are
      treated by incorporating the first-order self and exchange contributions into the
      random-phase approximation (RPA). Numerical results are presented for the spectra
      of the density response function and the plasmon dispersion for the gold wire on
      Si(557) substrate-a system studied recently by Nagao et al. (2006 Phys. Rev.
      Lett. 97 116802) for plasmons using electron energy loss spectroscopy. Our
      results for plasmons are found to agree with the experimental data. Though the
      first-order correction is small at currently accessible wire parameters, it
      becomes significant with increasing coupling parameter r(s). The effect of
      temperature on plasmons is found to be small for the wire system investigated
      experimentally. However, temperature has a significant effect on the spectra of
      the response function. We have also calculated the static structure factor, the
      pair-correlation function and the correlation energy at zero temperature in the
      first-order theory to check its applicability in dealing with correlations.
      Results are compared directly with the available Monte Carlo simulation data. It
      is found that the static correlation functions improve significantly over the RPA
      with the increase of r(s). On the other hand, the correlation energy shows very
      good agreement for r(s) <= 5 and wire widths b >= a(0). For smaller b, the
      agreement is good up to relatively smaller r(s).

PMID- 22609498
TI  - Suicide: leading cause of death among women in Nepal.

PMID- 22609499
TI  - Pheripheral airway responsiveness to sub-maximal exercise in asymptomatic
      cigarette smokers.
AB  - BACKGROUND: Cigarette smoking is one of the cardinal causes for the development
      of bronchial hyperresponsiveness among the smokers. OBJECTIVES: This study was
      perspectively designed to determine the peripheral bronchial responsiveness to
      sub-maximal exercise challenge in the asymptomatic smokers. METHODS: The subjects
      were between age of 18-25 years without any findings of cardiorespiratory
      diseases. We performed the 5 min step test exercise at intensity of 80 to 90% of
      maximum predicted heart rate in 42 young adult male asymptomatic smokers to
      examine the effect of cigarette smoking on airway responsiveness. Forced
      expiratory spirogram was recorded before and at 0, 5, 10, 15 min after the
      completion of exercise. Pre- to post exercise drop in Forced Expiratory Volume in
      first second >= 15% was considered hyperresponsive to the challenge. RESULT: The
      analysis of data (mean +/- SE) indicated the bronchial hyper-responsiveness in 22
      (52%) smokers. The post exercise recovery time pattern showed drop in forced
      expiratory spirogram from the resting baseline in the responsive smokers and the
      maximum percentage fall in the parameters or increase in airway resistance which
      reflect the peripheral airway integrity such as Forced Expiratory Flow 25% (20.30
      +/- 2.18 Vs 7.88 +/- 3.23, p < 0.01), Forced Expiratory Flow 50% (18.46 +/- 4.40
      Vs 1.93 +/- 2.78, p < 0.01), Forced Expiratory Flow 75% (23.94 +/- 3.68 Vs 0.80
      +/- 4.72, p < 0.001) and Forced Expiratory Flow 25-75% (32.50 +/- 4.79 Vs 3.64 +/
      3.32, p < 0.001) was significantly higher in the responsive than non-responsive
      subgroup of the smokers. CONCLUSION: The occurrence of peripheral airway
      resistance is more in the responsive than nonresponsive subset of smokers to the
      exercise challenge and hence more prone to develop obstructive airway disease in
      the long run.

PMID- 22609500
TI  - Age-related macular degeneration in Nepal.
AB  - BACKGROUND: The Age related Macular Degeneration (AMD) is a common cause of
      visual impairment and blindness worldwide in elderly. OBJECTIVE: This study aimed
      to explore the demographic characteristics, pattern and risk factors for AMD at a
      tertiary referral eye centre in Nepal. METHODS: This is a hospital-based
      prospective study, conducted at Tilganga Institute of Ophthalmology, Nepal from
      September 2008 to May 2009. All the consecutive cases of AMD diagnosed at the
      institute were included. RESULTS: A total of 141 patients (266 eyes) with AMD
      recruited for the study. The mean age was 69.5 years (9.1SD) with three fifth
      males (58.9%). Housewives and occupations like agriculture comprised of 38.3% and
      42.5% respectively. Three fourth (75.6%) of the patients were illiterate. The
      proportion of dry and wet AMD were found in 62.4% and 37.6% respectively.
      Bilateral involvement was seen in 88.7% of the subjects. Three fourth (71.4%) of
      the AMD eyes had presenting visual acuity less than 6/18. History of smoking was
      found in 69.9% of patients. Hypertension was the predominant systemic problem
      (45.4%) followed by diabetes mellitus (12.8%). CONCLUSION: AMD is correlated with
      ageing in our study as well. Dry AMD is more in age groups 45-64 years and wet
      AMD at 65 years and older. Bilateral involvement with one eye dry and fellow eye
      wet AMD is more predominant (44%). Smoking and occupations like agriculture and
      housewife are significant risk factors for AMD. Likewise male sex, illiteracy and
      hypertension are other risk factors for AMD in hospital settings.

PMID- 22609501
TI  - Propofol sedation during spinal anaesthesia- a dose finding study.
AB  - BACKGROUND: It is important to be able to measure and maintain a specific
      sedation level to compare outcomes of different levels of sedation during
      anesthesia and the aims include general patient comfort, freedom from specific
      discomfort, and some amnesia for both the block procedure and the surgical
      operation, in order to meet the patient preference and safety. In this
      prospective randomized clinical study, we compared the three different infusion
      doses of propofol. OBJECTIVE: To find out the appropriate infusion dose of
      propofol for optimal sedation without causing undue side effects in patients
      undergoing spinal anaesthesia. METHOD: One hundred twenty patients ASA PS I-II
      were randomly allocated to three groups 1, 2 and 3 receiving propofol infusion at
      the rate of 25, 50 and 75 microgram/kg/min with concentration of (0.5%), (1%) and
      (1.5%) respectively. They were observed for sedation score, hemodynamic
      parameters and satisfaction level. The adverse effects like respiratory
      depression, nausea and vomiting score were assessed. RESULT: Median sedation
      score increased in a dose dependent manner, with significantly higher scores in
      group 2 and 3 compared with group 1. Hemodynamic parameters were better in group
      1 and 2 as judged by mephentermine requirement. The awakening time after stoppage
      of infusion was significantly delayed in group 3 (p < 0.001). Respiratory
      depression, nausea and vomiting were comparable clinically. Almost three fourth
      of the patients were satisfied with the techniques used. CONCLUSION: Propofol
      infusion at the rate of 50 mcg/kg/min for sedation in spinal anaesthesia provides
      optimal sedation, early awakening and excellent satisfaction level in the
      postoperative period.

PMID- 22609502
TI  - Clinical, MRI and arthroscopic correlation in internal derangement of knee.
AB  - BACKGROUND: The traumatic or degenerative internal derangement of the knee
      requires certain investigations for the establishment of diagnosis, in addition
      to clinical history and a thorough physical examination. The use of arthrography
      and arthroscopy improves the accuracy of the diagnosis. MRI scanning of the knee
      joint has often been regarded as the noninvasive alternative to diagnostic
      arthroscopy. OBJECTIVE: The purpose of the study was to correlate clinical and
      low field MRI findings with arthroscopy in internal derangement of the knee.
      METHODS: Forty one patients with suspected internal derangement of the knee were
      subjected to MR examination followed by arthroscopy. Clinical criteria used were
      history, mode of injury, Mc Murray, Apley grinding, Thessaly test for meniscal
      injury. Drawer test was considered to be essential for clinical diagnosis of
      cruciate ligament injury. MRI of the knee was performed in low field open magnet
      (0.35T, Magnetom C, Seimens). Arthroscopy was done within two months of MR
      examination and was considered gold standard for the internal derangement of the
      knee. RESULTS: The sensitivity, specificity, diagnostic accuracy of clinical
      examination were 96.1%, 33.3% and 73.1% respectively for medial meniscal tear;
      38.4%, 96.4% and 78.1% respectively for lateral meniscal tear. The sensitivity,
      specificity, diagnostic accuracy of MRI were 92.3%,100% and 95.1% for medial
      meniscal tear; 84.6%96.4% and 92.6% respectively for lateral meniscal tear.
      CONCLUSION: Clinical examination showed higher sensitivity for medial meniscal
      tear compared to MRI, however with low specificity and diagnostic accuracy. Low
      field MRI showed high sensitivity, specificity, diagnostic accuracy for meniscal
      and cruciate ligament injury, in addition to associated derangement like
      articular cartilage damage, synovial thickening.

PMID- 22609503
TI  - Practices and perceptions on contraception acceptance among clients availing safe
      abortion services in Nepal.
AB  - BACKGROUND: The Government of Nepal has implemented safe abortion policy since
      2002. There are 245 approved sites providing safe abortion services to women
      across the country. Family planning counselling is one of the components of the
      safe abortion policy, which is important to reduce unwanted pregnancy, maternal
      morbidity and mortality due to the consequences of unsafe abortion and the
      service burden. OBJECTIVES: This study explains the perceptions, practices and
      factors affecting the use of family planning among abortion clients attending
      safe abortion services in Nepal. METHODS: A cross sectional study was carried out
      on September, 2008 enrolling 58 women who were waiting in the dressing room for
      safe abortion services in Paropkar Maternity Hospital, Nepal. All women attending
      hospital clinic for receiving safe abortion services were approached for
      interview till the targeted number was fulfilled. A convenience sampling was
      applied to reach the sample size. RESULTS: Of the 58 respondents, majority of the
      respondents were Hindus (83%), residing in Kathmandu district (76%); of the age
      group 20-29 years (69%); and 98% were married. One fifth (20.68 %) of the
      respondents had previous history of spontaneous or induced abortion. The main
      reason for abortion did not want any more babies/ complete family (45%). The
      knowledge of modern contraception was high (98.27%). The knowledge of emergency
      contraception was low (25.9%). Side effects was the main reason (48%, n=31) for
      discontinuation of contraceptives. Intention to use some modern family planning
      methods after the abortion was expressed by 83% clients. The major enabling
      factor for continued contraceptive use was the absence of side effects. The
      family planning counselling was acceptable for 91% clients. CONCLUSION:
      Knowledge, acceptance of counselling service and intention to use family planning
      measure was high in the study participants. There is need to provide skills on
      adapting with the adverse effect of family planning measure through continuous
      education and reinforcement.

PMID- 22609504
TI  - Pattern of renal cell carcinoma - a single center experience in Nepal.
AB  - BACKGROUND: Renal tumor is the 13th most common malignancy in the world and more
      than 90% of renal tumors are renal cell carcinomas. As there is no data available
      on renal cell carcinoma in Nepal, hence this study was undertaken to analyze the
      patterns of renal cell carcinoma in patients with renal mass at a tertiary level
      hospital in Nepal. OBJECTIVES: To analyze the patterns of renal cell carcinoma in
      patients with renal mass at a tertiary level hospital in Nepal. METHODS: The case
      records of 50 consecutive patients with renal cell carcinoma presenting at the
      Tribhuvan University Teaching Hospital, Kathmandu from July 2006 to June 2011
      were retrospectively evaluated for presenting symptoms, physical finding,
      investigation and histopathology report. RESULTS: Out of 50 patients, 64% were
      male and 36% were female. The age ranged between 11 to 78 years (mean +/- SD: 55
      +/- 15 years). Fifty four percent of patients were smokers. Incidentally tumor
      was detected in 40% cases by ultrasonography and the typical triad was present in
      only 4%. The tumor was occupying upper pole in 40% of cases. The tumor size
      ranged from 3 to 15 cm (mean +/- SD: 7.3 +/- 2.9 cm). Histopathologically, 76% of
      the patient had organ confined renal cell carcinoma (T1- 2 N0 M0). Clear cell was
      the most common type seen in 86%. Fuhrman nuclear grade 2 was found in 50%.
      CONCLUSION: Many of the renal cell carcinoma are detected incidentally, at an
      early stage and are of clear cell subtype.

PMID- 22609505
TI  - Effectiveness of teachers' training in assessment techniques: participants'
      perception.
AB  - BACKGROUND: Medical education has experienced a rapidly changing scenario
      especially during the past three decades. Teachers training programs have emerged
      in recent years as a more in depth and comprehensive mechanisms for strengthening
      instructional skills and formulating assessment techniques among faculty members.
      OBJECTIVE: The present study was carried out with the aim of assessing
      effectiveness of teacher training workshop on assessment techniques at B.P.
      Koirala Institute of Health sciences (BPKIHS), Dharan, Nepal. Methods: In this
      prospective questionnaire based study, the 26 entry level teachers were enrolled.
      They were requested to fill the questionnaire before and after the workshop on
      the assessment techniques at BPKIHS, Dharan. METHODS: Twenty six teachers
      majority of whom were entry level teachers comprising of medical, dental, nursing
      and allied sciences participated in pre- and post test analysis on the various
      components of written and oral examinations. A two and half days long training
      was conducted having 9 hours of teaching interactive sessions, 6 hours of group
      exercises, daily evaluation and 3 hours of presentation by participants. There
      was high degree of agreement with most topics of the assessment training.
      RESULTS: There was a significant gain in knowledge (p < 0.001) by the
      participants. All the participants (100%) agreed upon the training being
      informative and learned new things about assessment. More practice session with
      longer duration with invited resource persons were also suggested for an
      effective session. CONCLUSION: Thereis an immense opportunity for a better and
      comprehensive training in evaluation techniques in medical education..

PMID- 22609506
TI  - Morphometric analysis of clavicle in nepalese population.
AB  - BACKGROUND: Determining the sex of deceased is easy when a complete skeleton is
      available for examination. On the whole, the bones are heavier, larger and
      markings of muscular attachments are more pronounced in the male than in the
      female. OBJECTIVE: The purpose of this study was attempted to evolve an easily
      applied formula to enable the assessment of sex in an unknown clavicles and to
      know about comparative differences between the right and left clavicles, from
      certain metrical parameters. METHODS: The study was an observational, cross
      sectional and descriptive in nature. The present study was conducted on 257 adult
      clavicles out of which, 135 were of the right side and 122 of left side. The
      maximum length of the clavicle (in mm) was taken. RESULTS: The length of the
      right clavicles varies from 108 mm to 178 mm with an average of 143.21 mm +/-
      11.13 mm S.D. The length of the left clavicles varies from 111 mm to 181 mm with
      an average 145.53 mm +/- 11.04 mm S.D. It has been observed that the left
      clavicle was longer than the right clavicle by 2.32 mm. There was no such single
      character which can determine the sex of all clavicles. Depending on the length
      alone, the sex can be decided in 13.33% male and 4.44% female right clavicles and
      16.39% male and 9.83% female bones if the left clavicle is considered.
      CONCLUSION: The left clavicle was longer than the right clavicle. The
      determination of sex from the clavicle has a great medico legal significance to
      the toxicologists. It also helps the anthropologists in their study of evolution
      of mankind and migration of races.

PMID- 22609507
TI  - Intramedullary nailing for paediatric diaphyseal forearm bone fracture.
AB  - BACKGROUND: Though most of the pediatric diaphyseal forearm bone fracture can be
      treated with closed reduction and cast application, indications for operative
      intervention in pediatric both-bone forearm fractures include open fractures,
      irreducible fractures, and unstable fractures. Controversy exists as to what
      amount of angulation, displacement, and rotation constitutes an acceptable
      reduction. OBJECTIVE: To review union time and functional outcome of pediatric
      diaphyseal forearm bone fracture managed with intramedullary rush pin by closed
      or open reduction. METHODS: Fifty patients with both bone fracture of forearm
      were treated with intramedullary rush pin by closed or open reduction were
      included in the study and followed up for minimum six months for radiological and
      functional outcome. RESULTS: Out of 50 patients, 31 underwent closed reduction
      and 19 underwent open reduction. All fractures maintained good alignment post
      operatively. Forty seven patients had excellent results with normal elbow range
      of motion and normal forearm rotation and three patients had good results. In all
      patients good radiological union was seen in three months time. Eight patients
      had minor complications including skin irritation over prominent hardware,
      backing out of ulnar pin, superficial skin break down with exposed hardware.
      Twenty-three (46%) patients had undergone implant removal at an average of 6
      months (range 4-8 months) under regional or general anesthesia. CONCLUSION:
      Fixation with intramedullary rush pin for forearm fracture is an effective,
      simple, cheap, and convenient way for treatment in pediatric age group.

PMID- 22609508
TI  - Drug-receptor interactions.
AB  - In present-day pharmacology and medicine, it is usually taken for granted that
      cells contain a host of highly specific receptors. Drugs act on the cell membrane
      by physical and/or chemical interactions. This is usually through specific drug
      receptor sites known to be located on the membrane. These are defined as proteins
      on or within the cell that bind with specificity to particular drugs, chemical
      messenger substances or hormones and mediate their effects on the body. Today,
      the concept of specific receptors for drugs and transmitters lies at the very
      heart of pharmacology. However, it is only relatively recently that the notion of
      drug-specific receptors has become widely accepted, with considerable doubts
      being expressed about their existence as late as the 1960s.

PMID- 22609509
TI  - Needlesticks injuries in dentistry.
AB  - Needlestick injuries and other sharps-related injuries which expose health care
      professionals to bloodborne pathogens continue to be an important public health
      concern. Dentists are at increased risk of exposure to bloodborne pathogens,
      including Hepatitis B, Hepatitis C, and HIV. This article presents comprehensive
      information on Needlestick injuries (NSI), post exposure prophylaxis, precautions
      and suggestions for prevention of NSI in dentistry. Dentists should remember and
      apply many precautions to prevent the broad spectrum of sharps and splash
      injuries that could occur during the delivery of dental care.

PMID- 22609510
TI  - Preterm gestation along with partial hydatidiform mole and alive foetus.
AB  - Gestational trophoblastic disease encompasses a diverse group of lesion. If molar
      changes in the placenta are known along with an alive fetus then the situation is
      difficult to manage. We present successfully managed case of partial degeneration
      of placenta in molar pregnancy with an alive fetus at second stage of preterm
      labour.

PMID- 22609511
TI  - The journey of a journal.

PMID- 22609513
TI  - CE-MS for proteomics: Advances in interface development and application.
AB  - Capillary electrophoresis-mass spectrometry (CE-MS) has emerged as a powerful
      technique for the analysis of proteins and peptides. Over the past few years,
      significant progress has been made in the development of novel and more effective
      interfaces for hyphenating CE to MS. This review provides an overview of these
      new interfacing techniques for coupling CE to MS, covering the scientific
      literature from January 2007 to December 2011. The potential of these new CE-MS
      interfacing techniques is demonstrated within the field of (clinical) proteomics,
      more specifically "bottom-up" proteomics, by showing examples of the analysis of
      various biological samples. The relevant papers on CE-MS for proteomics are
      comprehensively summarized in tables, including, e.g. information on sample type
      and pretreatment, interfacing and MS detection mode. Finally, general conclusions
      and future perspectives are provided.

PMID- 22609512
TI  - Novel tyrosine phosphorylation sites in rat skeletal muscle revealed by
      phosphopeptide enrichment and HPLC-ESI-MS/MS.
AB  - Tyrosine phosphorylation plays a fundamental role in many cellular processes
      including differentiation, growth and insulin signaling. In insulin resistant
      muscle, aberrant tyrosine phosphorylation of several proteins has been detected.
      However, due to the low abundance of tyrosine phosphorylation (<1% of total
      protein phosphorylation), only a few tyrosine phosphorylation sites have been
      identified in mammalian skeletal muscle to date. Here, we used
      immunoprecipitation of phosphotyrosine peptides prior to HPLC-ESI-MS/MS analysis
      to improve the discovery of tyrosine phosphorylation in relatively small skeletal
      muscle biopsies from rats. This resulted in the identification of 87 distinctly
      localized tyrosine phosphorylation sites in 46 muscle proteins. Among them, 31
      appear to be novel. The tyrosine phosphorylated proteins included major enzymes
      in the glycolytic pathway and glycogen metabolism, sarcomeric proteins, and
      proteins involved in Ca(2+) homeostasis and phosphocreatine resynthesis. Among
      proteins regulated by insulin, we found tyrosine phosphorylation sites in
      glycogen synthase, and two of its inhibitors, GSK-3alpha and DYRK1A. Moreover,
      tyrosine phosphorylation sites were identified in several MAP kinases and a
      protein tyrosine phosphatase, SHPTP2. These results provide the largest catalogue
      of mammalian skeletal muscle tyrosine phosphorylation sites to date and provide
      novel targets for the investigation of human skeletal muscle phosphoproteins in
      various disease states.

PMID- 22609514
TI  - Comparison of diverse affinity based high-abundance protein depletion strategies
      for improved bio-marker discovery in oral fluids.
AB  - Oral fluids (OF) have been suggested as a source of biomarkers for oral and
      systemic health, but as with other bio-fluids, the presence of high-abundance
      proteins interferes with the detection of lower-abundance biomarkers. Here, we
      compared the performance of four depletion treatments: triple depletion (TD) of
      amylases, albumins and immunoglobulin G; multiple depletion (MD) of amylases and
      a panel of 20 proteins, a combination of the two (EMD) and combinatorial peptide
      ligand library based depletion termed CPLL. TD, MD, EMD and CPLL removed 76%,
      83%, 85% and 94% of total proteins, respectively, coupled with increased low
      abundance protein detection and narrowed dynamic range. 2-DE revealed that all
      depletion pretreatments successfully clarified areas hampered by high-abundance
      proteins; however, EMD and CPLL exposed the highest number of proteins.
      Quantitative MS of EMD samples relative to none treated samples indicated that
      most of downregulated proteins (>90%) were EMD target proteins. In conclusion, a
      multiple step EMD and CPLL depletion approaches bring about the highest number of
      protein detection ability and the best hampered-area clearance. As CPLL requires
      at least 10 fold more protein starting material, we suggest EMD pretreatment as a
      new detection tool in instances of low protein starting material.

PMID- 22609515
TI  - Supercooling and vitrification of aqueous glycerol solutions at normal and high
      pressures.
AB  - The supercooling and vitrification of aqueous glycerol solutions was studied at
      high pressures. Homogeneous ice nucleation temperatures (T(H)) were obtained for
      aqueous glycerol solutions of R=50, 30, 20, 12, and 10 (R: moles of water/moles
      of glycerol) up to 300MPa. The R=20 glycerol solution formed a glass above 200MPa
      at a cooling rate of 200 degrees C/min, indicating that pressure enhances glass
      formation of aqueous glycerol solutions. The (dT(g)/dP) values were obtained for
      vitrified aqueous glycerol solutions of R=3, 5, 10, and 20. These data can be
      used for the development of cryo-preservation liquids for living cells at high
      pressures.

PMID- 22609516
TI  - Viscosity of supercooled aqueous glycerol solutions, validity of the Stokes
      Einstein relationship, and implications for cryopreservation.
AB  - The viscosity of supercooled glycerol aqueous solutions, with glycerol mass
      fractions between 0.70 and 0.90, have been determined to confirm that the Avramov
      Milchev equation describes very well the temperature dependence of the viscosity
      of the binary mixtures including the supercooled regime. On the contrary, it is
      shown that the free volume model of viscosity, with the parameters proposed in a
      recent work (He, Fowler, Toner, J. Appl. Phys. 100 (2006) 074702), overestimates
      the viscosity of the glycerol-rich mixtures at low temperatures by several orders
      of magnitude. Moreover, the free volume model for the water diffusion leads to
      predictions of the Stokes-Einstein product, which are incompatible with the
      experimental findings. We conclude that the use of these free volume models, with
      parameters obtained by fitting experimental data far from the supercooled and
      glassy regions, lead to incorrect predictions of the deterioration rates of
      biomolecules, overestimating their life times in these cryopreservation media.

PMID- 22609517
TI  - Developmental cigarette smoke exposure: liver proteome profile alterations in low
      birth weight pups.
AB  - Cigarette smoke is composed of over 4000 chemicals many of which are strong
      oxidizing agents and chemical carcinogens. Chronic cigarette smoke exposure (CSE)
      induces mild alterations in liver histology indicative of toxicity though the
      molecular pathways underlying these alterations remain to be explored. Utilizing
      a mouse model of 'active' developmental CSE (gestational day (GD) 1 through
      postnatal day (PD) 21; cotinine >50ng/mL) characterized by low birth weight
      offspring, the impact of developmental CSE on liver protein abundances was
      determined. On PD21, liver tissue was collected from pups for 2D SDS-PAGE based
      proteome analysis with statistical analysis by Partial Least Squares-Discriminant
      Analysis (PLS-DA). Protein spots of interest were identified by ESI-MS/MS with
      impacted molecular pathways identified by Ingenuity Pathway Analysis.
      Developmental CSE decreased the abundance of proteins associated with the small
      molecule biochemistry (includes glucose metabolism), lipid metabolism, amino acid
      metabolism, and inflammatory response pathways. Decreased gluconeogenic enzyme
      activity and lysophosphatidylcholine availability following developmental CSE
      were found and supports the impact of CSE on these pathways. Proteins with
      increased abundance belonged to the cell death and drug metabolism networks.
      Liver antioxidant enzyme abundances [glutathione-S-transferase (GST) and
      peroxiredoxins] were also altered by CSE, but GST enzymatic activity was
      unchanged. In summary, cigarette smoke exposure spanning pre- and post-natal
      development resulted in persistent decreased offspring weights, decreased
      abundances of liver metabolic proteins, decreased gluconeogenic activity, and
      altered lipid metabolism. The companion paper details the kidney proteome
      alterations in the same offspring.

PMID- 22609518
TI  - Multilocus sequence typing and repetitive-sequence-based PCR (DiversiLab) for
      molecular epidemiological characterization of Propionibacterium acnes isolates of
      heterogeneous origin.
AB  - Propionibacterium acnes is a gram-positive bacillus predominantly found on the
      skin. Although it is considered an opportunistic pathogen it is also been
      associated with severe infections. Some specific P. acnes subtypes are
      hypothesized to be more prone to cause infection than others. Thus, the aim of
      the present study was to investigate the ability to discriminate between P. acnes
      isolates of a refined multilocus sequence typing (MLST) method and a genotyping
      method, DiversiLab, based on repetitive-sequence-PCR technology. The MLST and
      DiversiLab analysis were performed on 29 P. acnes isolates of diverse origins;
      orthopedic implant infections, deep infections following cardiothoracic surgery,
      skin, and isolates from perioperative tissue samples from prostate cancer.
      Subtyping was based on recA, tly, and Tc12S sequences. The MLST analysis
      identified 23 sequence types and displayed a superior ability to discriminate P.
      acnes isolates compared to DiversiLab and the subtyping. The highest
      discriminatory index was found when using seven genes. DiversiLab was better able
      to differentiate the isolates compared to the MLST clonal complexes of sequence
      types. Our results suggest that DiversiLab can be useful as a rapid typing tool
      for initial discrimination of P. acnes isolates. When better discrimination is
      required, such as for investigations of the heterogeneity of P. acnes isolates
      and its involvement in different pathogenic processes, the present MLST protocol
      is valuable.

PMID- 22609519
TI  - Identification and characterization of WhiB-like family proteins of the
      Bifidobacterium genus.
AB  - Bifidobacteria are strictly anaerobic bacteria, that are an important component
      of human microbiote due to their probiotic characteristics. They are frequently
      exposed to a variety of stresses, therefore, identification of genes implicated
      in stress responses in bifidobacteria is critical for biomedicine and maintenance
      of industrial strains. The WhiB-like family proteins unique for Actinobacteria
      are transcriptional regulators involved in major cellular processes, including
      stress responses. The aim of this study was the identification of WhiB-like
      family proteins of the Bifidobacterium genus of the Actinobacteria class and
      functional characterization of conservative whiB-like genes. The DNA sequence
      database of 36 strains revealed a family of WhiB-encoding genes. It were
      identified the wblE orthologs in all Bifidobacteria species and the whiB2
      orthologs in all bifidobacterial strains except of all strains of Bifidobacterium
      animalis subsp. lactis and Bifidobacterium gallicum. Some strains, in particular,
      those of the Bifidobacterium longum group, contain additional whiB-like genes of
      different length and a low degree of similarity in sequences. The wblE and whiB2
      genes of the Bifidobacterium genus are evolutionary conservative and ancient
      genes. The real-time PCR analysis showed that transcription of wblE is induced by
      a variety of stress conditions such as heat shock, osmotic, oxidative stresses,
      by antibiotic tetracycline and bile salt treatment, the nutrient starvation and
      entry into late stationary phase. The wblE gene may play a significant role in
      general stress responses in bifidobacteria.

PMID- 22609520
TI  - Identification of two novel mutations in the SLC4A1 gene in two unrelated Chinese
      families with distal renal tubular acidosis.
AB  - BACKGROUND AND AIMS: Distal renal tubular acidosis (dRTA) is characterized by a
      reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic
      acidosis, nephrocalcinosis, and nephrolithiasis. Mutations in the SLC4A1 gene
      have been found to cause either autosomal dominant (AD) or autosomal recessive
      (AR) dRTA. METHODS: Four affected individuals and nine healthy family members
      from two unrelated Chinese families with dRTA were clinically studied. The SLC4A1
      gene was screened and analyzed, and the mutations were confirmed using molecular
      genetic techniques. RESULTS: In family1, the affected individuals had novel
      compound heterozygous SLC4A1 G494S/G701D mutations inherited from their
      clinically normal heterozygous father and mother, respectively. In family 2, the
      affected individuals exhibited a novel 3-bp duplication (c.2715_2717dupCGA) in
      exon 20 of SLC4A1 that led to the D905dup mutation. The age of presentation was
      younger, hypokalemia was more severe, and growth retardation was more severe in
      recessive patients in family 1 than patients with AD dRTA in family 2.
      CONCLUSIONS: This is the first report of dRTA patients with compound heterozygous
      conditions in mainland China. Two novel SLC4A1 mutations (G494S and D905dup) were
      identified. Our results confirm the importance of the C-terminal residues of the
      SLC4A1 gene product in normal acidification processes and indicate that mutations
      in this region are likely to result in AD dRTA. Our study extends the mutation
      spectrum of dRTA and is helpful in early molecular diagnoses of dRTA.

PMID- 22609522
TI  - Amino acids potentiate insulin signaling in CHO-K1 at high glucose conditions.
AB  - BACKGROUND AND AIMS: Amino acids reportedly increase the glucose uptake under
      high glucose conditions. However, there are controversies in the role of amino
      acids in diabetes mellitus. The present study explores the insulin signaling
      pathway involved in glucose uptake mediated by amino acids in CHO-K1 cells.
      METHODS: CHO-K1 cells were exposed to normal (7 mM) and high glucose (17 and 27
      mM) with 100 nM insulin in the presence and absence of amino acid mixtures (AAM)
      in varying concentration (5 and 20 mM) followed by the assays, insulin receptor
      tyrosine kinase (IRTK) and phosphatidylinositol 3 kinase (PI3K) by
      autoradiography, protein kinase B (Akt) and glucose transporter (GLUT4) by
      Western blot and glycogen synthase (GS) by HPLC. RESULTS: The addition of 5 and
      20 mM AAM significantly increased IRTK and PI3K activity (ANOVA p = 0.025, p =
      0.003, respectively) with increasing glucose concentration. Addition of 5 mM AAM
      in the presence of normal glucose significantly increased the levels of
      phosphorylated Akt Ser473 (p = 0.02) with no significant change at high glucose.
      At 20 mM AAM there was a significant decrease in Akt phosphorylation (p = 0.035)
      that was increased by high glucose concentration. GLUT4 protein levels were
      increased with AAM (5 mM) along with increase in glycogen synthase activity at
      all glucose concentrations (p <0.05). CONCLUSIONS: Amino acids as a mixture is
      beneficial in augmenting insulin signaling pathway via IRTK/PI3K/GLUT4 pathway
      along with activation of GS in CHO-K1 cells, thereby ensuring increased
      intracellular glucose availability.

PMID- 22609524
TI  - Improving the double quantum filtered COSY experiment by "Moving Tube" NMR.
AB  - Most 2D NMR spectra show artifacts that become increasingly more prominent as the
      relaxation delay between transients is decreased. Additionally, "rushing" a 2D
      experiment may lead to reduced sensitivity. It is shown here how to collect a DQF
      COSY spectrum in less time, without artifacts, and with improved sensitivity, by
      a hardware solution we call Moving Tube NMR (MT NMR): the sample volume is
      physically moved out of the receiver coil after each transient and replaced by a
      fresh aliquot that is nearer to the equilibrium magnetization M(0). MT NMR was
      implemented with an automated mechanism that gave accurate and reproducible
      vertical tube movement, and a very long 5mm outer diameter (OD) NMR tube to hold
      a larger sample volume. Comparison of conventional and MT NMR DQF-COSY showed
      increased sensitivity and far reduced artifacts in the latter. The so-called t(1)
      noise in the MT spectrum was no worse than in the conventional spectrum, pointing
      to the excellent specifications of the long 5mm OD tube, and the good mechanical
      handling of the automated drive. Thus, MT NMR could improve throughput for
      routine 2D NMR experiments without reducing sensitivity or adding artifacts, if
      sufficient sample is available. MT NMR could also be useful in cases of limited
      solubility, or for nuclei with long T(1) relaxation times.

PMID- 22609523
TI  - Beta1-adrenergic receptors promote focal adhesion signaling downregulation and
      myocyte apoptosis in acute volume overload.
AB  - Numerous studies demonstrated increased expression of extracellular matrix (ECM)
      proteins and activation of focal adhesion (FA) signaling pathways in models of
      pressure overload-induced cardiac hypertrophy. However, little is known about FA
      signaling in response to volume overload where cardiac hypertrophy is associated
      with ECM loss. This study examines the role of beta1-adrenergic receptors
      (beta(1)-ARs) in FA signaling changes and myocyte apoptosis induced during acute
      hemodynamic stress of volume overload. Rats with eccentric cardiac hypertrophy
      induced after aorto-caval fistula (ACF) develop reduced interstitial collagen
      content and decreased tyrosine phosphorylation of key FA signaling molecules FAK,
      Pyk(2) and paxillin along with an increase in cardiac myocyte apoptosis. ACF also
      increased activation of PTEN, a dual lipid and protein phosphatase, and its
      interaction with FA proteins. beta(1)-AR blockade (extended-release of metoprolol
      succinate, 100mg QD) markedly attenuated PTEN activation, restored FA signaling
      and reduced myocyte apoptosis induced by ACF at 2days, but failed to reduce
      interstitial collagen loss and left ventricular dilatation. Treating cultured
      myocytes with beta(1)-AR agonists or adenoviral expression of beta(1)-ARs caused
      PTEN activation and interaction with FA proteins, thus leading to FA signaling
      downregulation and myocyte apoptosis. Adenoviral-mediated expression of a
      catalytically inactive PTEN mutant or wild-type FAK restored FA signaling
      downregulation and attenuated myocyte apoptosis induced by beta(1)-ARs.
      Collectively, these data show that beta(1)-AR stimulation in response to ACF
      induces FA signaling downregulation through an ECM-independent mechanism. This
      effect involves PTEN activation and may contribute to adverse cardiac remodeling
      and function in the course of volume overload.

PMID- 22609525
TI  - An analysis of NMR sensitivity enhancements obtained using non-uniform weighted
      sampling, and the application to protein NMR.
AB  - Non-uniform weighted sampling (NUWS) is a sampling strategy, related to non
      uniform sampling (NUS) in the limit of long acquisition times, in which each
      indirect increment of a multidimensional spectrum is sampled multiple times
      according to some weighting function. As the spectrum is fully sampled it can be
      processed in a conventional manner by the discrete Fourier transform, making the
      analysis of sensitivity much more straightforward than for NUS data. Previously,
      2-3 fold increases in signal-to-noise ratio (SNR) have been reported using NUWS.
      However, as the sampling schedule acts as a window function, the observed SNR
      must be compared with uniformly sampled data apodized using the same weighting
      function. On doing this, we calculate more modest improvements of 10-20% in SNR,
      and these are verified experimentally for spectra of alpha-synuclein and YFP.
      Nevertheless, we prove that NUWS always improves the sensitivity compared with
      identically processed uniformly sampled data, and when combined with rapid
      recycling experiments such as the SOFAST-HMQC, NUWS methods have the potential to
      make a useful and practical contribution to sensitivity-limited measurements.

PMID- 22609526
TI  - Anti-inflammatory activity and percutaneous absorption of quercetin and its
      polymethoxylated compound and glycosides: the relationships to chemical
      structures.
AB  - The potential of quercetin-related compounds for topical application has not
      previously been systematically investigated. To better elucidate relationships of
      the structure and activity with skin permeation, some quercetin compounds were
      used as permeants, including aglycone, a polymethoxylated compound (quercetin
      3,5,7,3',4'-pentamethylether, QM), and seven glycosides. Quercetin and the
      glycoside with glucopyranuronic acid (Q4) at a dose of 30 MUM completely
      inhibited superoxide anion activated neutrophils. QM also potentially suppressed
      superoxide by 90%. Both quercetin and QM showed inhibitory activity on elastase
      release with respective IC(50) values of 6.25 and 15.76 MUM. Glycosylation
      significantly diminished this activity. Both an infinite concentration and
      saturated solubility in pH 7 buffer were used as permeant doses for the in vitro
      permeation experiments. The flux or permeability coefficient, which is the
      indicator for total absorption of dermal delivery due to the use of nude mouse
      skin, was the greatest for QM, followed by the glycosides and quercetin. QM
      showed 26* greater flux compared to quercetin. No penetration of quercetin
      occurred at the dose of saturated solubility. Rutin generally exhibited the
      highest skin permeation among the glycosides. It was found that the glycoside
      enantiomers (Q2 and Q3) revealed completely different permeation profiles. The
      stratum corneum was the principal penetration barrier for quercetin and its
      glycosides but not QM. Rutin provoked some skin redness and inflammation after a
      5-day administration in nude mouse. QM caused no irritation, suggesting that it
      is a superior candidate for topical delivery.

PMID- 22609527
TI  - Photoinactivation of Staphylococcus epidermidis biofilms and suspensions by the
      hydrophobic photosensitizer curcumin--effect of selected nanocarrier: studies on
      curcumin and curcuminoides XLVII.
AB  - Solubilization and stabilization from rapid degradation by the use of
      nanocarriers are necessary to exploit curcumin's phototoxic potential towards
      pathogenic bacteria. However, maintenance of the phototoxicity requires a careful
      selection of type and amount of nanocarrier. The phototoxicity of an aqueous
      supersaturated curcumin solution without nanocarrier was compared to that of
      curcumin solubilized in polyethylene glycol 400 (PEG 400), Pluronic(r) F 127 (F
      127) and hydroxypropyl-gamma-cyclodextrin (HPgammaCD) on Staphylococcus (S.)
      epidermidis biofilms and suspensions. The nanocarriers stabilized the hydrophobic
      photosensitizer (PS) towards physical precipitation and hydrolytic degradation;
      however, photobleaching was pronounced (46-100% degradation) after irradiation
      with a dose of ~ 9 J/cm(2) blue light depending on selected nanocarrier. Complete
      inactivation of S. epidermidis in suspension was achieved after exposure of ~ 5
      J/cm(2) combined with curcumin in 20% PEG 400 and 0.5% HPgammaCD and less than
      1J/cm(2) light in case of a supersaturated curcumin solution. Curcumin in 1.5% F
      127 induced phototoxicity towards bacterial biofilms; however, it was not
      phototoxic towards planktonic S. epidermidis. All curcumin preparations
      investigated demonstrated significant and similar phototoxicity towards biofilms
      (13-29% bacterial survival). A ~ 9 J/cm(2) light dose was not sufficient to
      eradicate S. epidermidis biofilm completely under the current conditions.

PMID- 22609528
TI  - Emodin induces embryonic toxicity in mouse blastocysts through apoptosis.
AB  - Emodin (1,3,8-trihydroxy-6-methylanthraquinone), a major constituent of rhubarb,
      has a wide range of therapeutic applications. Previous studies have established
      that emodin inhibits cell proliferation and induces caspase 3-dependent
      apoptosis. However, its side-effects, particularly those on embryonic
      development, have not been well characterized as yet. In the current study, we
      examined the cytotoxic effects of emodin on mouse embryos at the blastocyst
      stage, subsequent embryonic attachment and outgrowth in vitro, and in vivo
      implantation by embryo transfer. Blastocysts treated with 25-75 MUM emodin
      exhibited significantly increased apoptosis and a corresponding decrease in total
      cell number. Notably, the implantation success rate of blastocysts pretreated
      with emodin was lower than that of their control counterparts. Moreover, in vitro
      treatment with 25-75 MUM emodin was associated with increased resorption of post
      implantation embryos and decreased fetal weight. With the aid of an in vivo mouse
      model, we showed that consumption of drinking water containing emodin led to
      apoptosis and decreased cell proliferation, and inhibited early embryonic
      development to the blastocyst stage. Our findings support a degree of selective
      inhibition of retinoic acid receptors in blastocysts treated with emodin. In
      addition, emodin appears to induce injury in mouse blastocysts through intrinsic
      apoptotic signaling processes to impair sequent embryonic development. These
      results collectively indicate that emodin has the potential to induce embryonic
      cytotoxicity.

PMID- 22609529
TI  - Analysis of collection systems for sorted household waste in Spain.
AB  - This work analyses the separate collection systems used in Spanish towns with
      between 5000 and 50,000 inhabitants. The study looks at the systems and their
      efficiency by means of the indicators fractioning rate, quality in container rate
      and separation rate. The results obtained are compared with those from a similar
      study conducted earlier that was applied to towns and cities with populations
      over 50,000. It can be concluded that the most widely implemented system in Spain
      involves the collection of mixed waste from kerbside bins and picking up
      paper/cardboard, glass and lightweight packaging from drop-off points. Findings
      show that the best system is the one that collects mixed waste, organic material
      and multiproduct waste door-to-door, and glass from drop-off points. The
      indicator separation rate made it possible to establish beta regression models to
      analyse the influence of the following logistic variables: inhabitants per point
      (people/pt), time (years) and frequency of collection (freq). From these models
      it can be seen that people/pt has a negative effect on all the fractions, while
      freq and years have a positive effect in the case of paper.

PMID- 22609530
TI  - Thermal and thermo-chemical pre-treatment of four waste residues and the effect
      on acetic acid production and methane synthesis.
AB  - In this study four diverse solid waste substrates (coal, Kraft pulp solids,
      chicken feathers and chicken processing waste) were thermally pre-treated (70,
      140 and 200  degrees C), under an inert (nitrogen) or oxidative (oxygen)
      atmosphere, and then anaerobically digested. Membrane inlet mass spectrometry
      during the thermal and thermo-chemical reactions was successfully used to
      establish oxygen and carbon dioxide gas fluxes and product formation (acetic
      acid). There was significant solids hydrolysis pre-treatment at 200  degrees C
      under an oxidative atmosphere, as indicated by a decrease in the volatile
      suspended solids and an increase in dissolved organic carbon. Greater
      concentrations of volatile fatty acids were produced under oxidative conditions
      at higher temperatures. The methane yield more than tripled for feathers after
      pre-treatment at 140  degrees C (under both atmospheres), but decreased after
      oxidative pre-treatment at 200  degrees C, due to the destruction of available
      carbon by the thermo-chemical reaction. Methane yield more than doubled for the
      Kraft pulp solids with the 200  degrees C pre-treatment under oxidative
      conditions. This study illustrated the power of wet oxidation for solids
      destruction and its potential to improve methane yields generated during
      anaerobic digestion.

PMID- 22609531
TI  - Envenomation by spiders of the genus Hololena (Araneae: Agelenidae).
AB  - Three verified bites from Hololena spiders (Family Agelenidae) are presented
      here. Two male victims, each over 100 kg weight (bitten by female spiders),
      experienced headaches and 4-h episodes of vomiting. A female bite victim (bitten
      by a male spider) experienced minor reaction. None sought medical attention;
      symptoms resolved in a few days. Although these incidents were not serious,
      reactions in the male victims were more dynamic than usual generic spider bites
      (minor edema, minor erythema).

PMID- 22609532
TI  - Hybrid proteins of Cobra Venom Factor and cobra C3: tools to identify
      functionally important regions in Cobra Venom Factor.
AB  - Cobra Venom Factor (CVF) is the complement-activating protein in cobra venom. CVF
      is structurally and functionally highly homologous to complement component C3.
      CVF, like C3b, the activated form of C3, forms a bimolecular complex with Factor
      B in serum, called C3/C5 convertase, an enzyme which activates complement
      components C3 and C5. Despite the high degree of homology, the two C3/C5
      convertases exhibit significant functional differences. The most important
      difference is that the convertase formed with CVF (CVF,Bb) is physico-chemically
      far more stable than the convertase formed with C3b (C3b,Bb). In addition, the
      CVF,Bb convertase and CVF are completely resistant to inactivation by the
      complement regulatory proteins Factor H and Factor I. Furthermore, the CVF,Bb
      enzyme shows efficient C5-cleaving activity in fluid phase. In contrast, the
      C3b,Bb enzyme is essentially devoid of fluid-phase C5-cleaving activity. By
      taking advantage of the high degree of sequence identity at both the amino acid
      (85%) and DNA levels (93%) between CVF and cobra C3, we created hybrid proteins
      of CVF and cobra C3 where sections, or only a few amino acids, of the CVF
      sequence were replaced with the homologous amino acid sequence of cobra C3. In a
      first set of experiments, we created five hybrid proteins, termed H1 through H5,
      where the cobra C3 substitutions collectively spanned the entire length of the
      CVF protein. We also created three additional hybrid proteins where only four or
      five amino acid residues in CVF were exchanged with the corresponding amino acid
      residues from cobra C3. Collectively, these hybrid proteins, representing loss-of
      function mutants of CVF, allowed the identification of regions and individual
      amino acid residues important for the CVF-specific functions. The results include
      the observation that the CVF beta-chain is crucially important for forming a
      stable convertase, whereas the CVF alpha-chain appears to harbor no CVF-specific
      functions. Furthermore, the CVF gamma-chain is additionally important for the
      fluid-phase C5-cleaving activity of CVF,Bb. Interestingly, the structural changes
      in the individual hybrid proteins differentially affected the molecular functions
      of the CVF,Bb enzyme such as convertase formation, C3 cleavage, and C5 cleavage.

PMID- 22609533
TI  - Self-organizing high-order cognitive functions in artificial agents: implications
      for possible prefrontal cortex mechanisms.
AB  - In our daily life, we often adapt plans and behaviors according to dynamically
      changing world circumstances, selecting activities that make us feel more
      confident about the future. In this adaptation, the prefrontal cortex (PFC) is
      believed to have an important role, applying executive control on other cognitive
      processes to achieve context switching and confidence monitoring; however, many
      questions remain open regarding the nature of neural processes supporting
      executive control. The current work explores possible mechanisms of this high
      order cognitive function, transferring executing control in the domain of
      artificial cognitive systems. In particular, we study the self-organization of
      artificial neural networks accomplishing a robotic rule-switching task analogous
      to the Wisconsin Card Sorting Test. The obtained results show that behavioral
      rules may be encoded in neuro-dynamic attractors, with their geometric
      arrangements in phase space affecting the shaping of confidence. Analysis of the
      emergent dynamical structures suggests possible explanations of the interactions
      of high-level and low-level processes in the real brain.

PMID- 22609534
TI  - A fast and adaptive automated disease diagnosis method with an innovative neural
      network model.
AB  - Automatic disease diagnosis systems have been used for many years. While these
      systems are constructed, the data used needs to be classified appropriately. For
      this purpose, a variety of methods have been proposed in the literature so far.
      As distinct from the ones in the literature, in this study, a general-purpose,
      fast and adaptive disease diagnosis system is developed. This newly proposed
      method is based on Learning Vector Quantization (LVQ) artificial neural networks
      which are powerful classification algorithms. In this study, the classification
      ability of LVQ networks is developed by embedding a reinforcement mechanism into
      the LVQ network in order to increase the success rate of the disease diagnosis
      method and reduce the decision time. The parameters of the reinforcement learning
      mechanism are updated in an adaptive way in the network. Thus, the loss of time
      due to incorrect selection of the parameters and decrement in the success rate
      are avoided. After the development process mentioned, the newly proposed
      classification technique is named "Adaptive LVQ with Reinforcement Mechanism
      (ALVQ-RM)". The method proposed handles data with missing values. To prove that
      this method did not offer a special solution for a particular disease, because of
      its adaptive structure, it is used both for diagnosis of breast cancer, and for
      diagnosis of thyroid disorders, and a correct diagnosis rate after replacing
      missing values using median method over 99.5% is acquired in average for both
      diseases. In addition, the success rate of determination of the parameters of the
      proposed "LVQ with Reinforcement Mechanism (LVQ-RM)" classifier, and how this
      determination affected the required number of iterations for acquiring that
      success rate are discussed with comparison to the other studies.

PMID- 22609535
TI  - New caged neurotransmitter analogs selective for glutamate receptor sub-types
      based on methoxynitroindoline and nitrophenylethoxycarbonyl caging groups.
AB  - Photolysis is widely used in experimental neuroscience to isolate post-synaptic
      receptor activation from presynaptic processes, to determine receptor mechanisms
      in situ, for pharmacological dissection of signaling pathways, or for
      photostimulation/inhibition in neural networks. We have evaluated new caged
      neuroactive amino acids that use 4-methoxy-7-nitroindolinyl- (MNI) or 1-(2
      nitrophenyl)ethoxycarbonyl (NPEC) photoprotecting groups to make caged ligands
      specific for glutamate receptor sub-types. Each was tested for interference with
      synaptic transmission and excitability and for receptor-specific actions in slice
      preparations. No adverse effects were found at glutamate receptors. At high
      concentration, MNI-caged, but not NPEC-caged ligands, interfered with GABA-ergic
      transmission. MNI-caged amino acids have sub-microsecond release times suitable
      for investigating mechanisms at fast synaptic receptors in situ. MNI-NMDA and MNI
      kainate were synthesized and tested. MNI-NMDA showed stoichiometric release of
      chirally pure NMDA. Wide-field photolysis in cerebellar interneurons produced a
      fast-rising sustained activation of NMDA receptors, and localized laser
      photolysis gave a fast, transient response. Photolysis of MNI-kainate to release
      up to 4 MUM kainate generated large inward currents at resting membrane potential
      in Purkinje neurons. Application of GYKI 53655 indicated that 40% of the current
      was due to AMPA receptor activation by kainate. Signaling via metabotropic
      glutamate receptors (mGluR) does not require fast release rates. NPEC cages are
      simpler to prepare but have slower photorelease. Photolysis of NPEC-ACPD or NPEC
      DHPG in Purkinje neurons generated slow inward currents blocked by the mGluR type
      1 antagonist CPCCOEt similar to the slow sEPSC seen with parallel fiber burst
      stimulation. NPEC-AMPA was also tested in Purkinje neurons and showed large
      sustained inward currents selective for AMPA receptors with little activation of
      kainate receptors. MNI-caged l-glutamate, NMDA and kainate inhibit GABA-A
      receptors with IC50 concentrations close to the maximum concentrations useful in
      receptor signaling experiments.

PMID- 22609536
TI  - Impact of early-life stress, on group III mGlu receptor levels in the rat
      hippocampus: effects of ketamine, electroconvulsive shock therapy and fluoxetine
      treatment.
AB  - The glutamatergic system is increasingly being viewed as a promising target for
      the development of novel treatments for depression. The group III metabotropic
      glutamate (mGlu) receptors (mGlu(4, 7) and (8) receptors) in particular are
      beginning to show promise in this respect. It remains unclear how antidepressant
      medications modulate mGlu receptors. In this study we investigated the effects of
      three antidepressant treatments (fluoxetine, ketamine and electroconvulsive shock
      therapy (ECT)). Ketamine is an NMDA receptor antagonist which possess a rapid
      antidepressant therapeutic profile and moreover is effective in cases of
      treatment-resistant depression. Furthermore, ECT is also a therapeutic strategy
      possessing increased efficacy compared to conventional monoamine based therapies.
      The effect these two highly efficacious treatments have on hippocampal group III
      mGlu receptors remains completely unexplored. To redress this deficit we
      investigated the effects these treatments and the prototypical selective
      serotonin reuptake inhibitor (SSRI) fluoxetine would have on hippocampal group
      III mGlu receptor mRNA levels in naive Sprague-Dawley rats and rats which had
      undergone early-life stress in the form of the maternal separation (MS)
      procedure. We found MS significantly reduced mGlu(4) receptor expression and
      fluoxetine reversed this MS induced change. ECT and ketamine treatment
      significantly reduced mGlu(4) receptor expression in non-separated (NS) animals
      while having no effect in MS animals. Fluoxetine and ECT significantly increased
      mGlu(7) receptor expression in NS animals. This work demonstrates changes to
      mGlu(4) receptor expression may be a lasting molecular change which occurs due to
      early-life stress. Taken together our data shows there are selective changes to
      group III mGlu receptors under basal and early-life stress conditions. This
      article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'.

PMID- 22609538
TI  - You give me the chills: embodied reactions to inappropriate amounts of behavioral
      mimicry.
AB  - In the research reported here, we investigated how suspicious nonverbal cues from
      other people can trigger feelings of physical coldness. There exist implicit
      standards for how much nonverbal behavioral mimicry is appropriate in various
      types of social interactions, and individuals may react negatively when
      interaction partners violate these standards. One such reaction may be feelings
      of physical coldness. Participants in three studies either were or were not
      mimicked by an experimenter in various social contexts. In Study 1, participants
      who interacted with an affiliative experimenter reported feeling colder if they
      were not mimicked than if they were, and participants who interacted with a task
      oriented experimenter reported feeling colder if they were mimicked than if they
      were not. Studies 2 and 3 demonstrated that it was not the amount of mimicry per
      se that moderated felt coldness; rather, felt coldness was moderated by the
      inappropriateness of the mimicry given implicit standards set by individual
      differences (Study 2) and racial differences (Study 3). Implications for everyday
      subjective experience are discussed.

PMID- 22609537
TI  - Age and gender dependent bioavailability of R- and R,S-alpha-lipoic acid: a pilot
      study.
AB  - Lipoic acid (LA) shows promise as a beneficial micronutrient toward improving
      elder health. Studies using old rats show that (R)-alpha-LA (R-LA) significantly
      increases low molecular weight antioxidants that otherwise decline with age.
      Despite this rationale for benefiting human health, little is known about age
      associated alterations in absorption characteristics of LA, or whether the
      commercially available racemic mixture of LA (R,S-LA) is equally as bioavailable
      as the naturally occurring R-enantiomer. To address these discrepancies, a pilot
      study was performed to establish which form of LA is most effectively absorbed in
      older subjects relative to young volunteers. Young adults (average age=32 years)
      and older adults (average age=79 years) each received 500 mg of either R- or R,S
      LA. Blood samples were collected for 3h after supplementation. After a washout
      period they were given the other chiral form of LA not originally ingested.
      Results showed that 2 out of 6 elder males exhibited greater maximal plasma LA
      and area under the curve for the R-form of LA versus the racemic mixture. The
      elder subjects also demonstrated a reduced time to reach maximal plasma LA
      concentration following R-LA supplementation than for the racemic mixture. In
      contrast, young males had a tendency for increased bioavailability of R,S-LA.
      Overall, bioavailability for either LA isoform was much more variable between
      older subjects compared to young adults. Plasma glutathione levels were not
      altered during the sampling period. Thus subject age, and potential for varied
      response, should be considered when determining an LA supplementation regimen.

PMID- 22609539
TI  - Stereotype threat strengthens automatic recall and undermines controlled
      processes in older adults.
AB  - The threat of being judged stereotypically (stereotype threat) may impair memory
      performance in older adults, thereby producing inflated age differences in memory
      tasks. However, the underlying mechanisms of stereotype threat in older adults or
      other stigmatized groups remain poorly understood. Here, we offer evidence that
      stereotype threat consumes working memory resources in older adults. More
      important, using a process-dissociation procedure, we found, for the first time,
      that stereotype threat undermines the controlled use of memory and simultaneously
      intensifies automatic response tendencies. These findings indicate that competing
      models of stereotype threat are actually compatible and offer further reasons for
      researchers and practitioners to pay special attention to age-related stereotypes
      during standardized neuropsychological testing.

PMID- 22609540
TI  - Tinnitus retraining therapy:  mixing point and total masking are equally
      effective.
AB  - OBJECTIVES: Habituation to tinnitus cannot occur with total masking, an argument
      made by proponents of "tinnitus retraining therapy." We also compared the
      effectiveness of retraining therapy with mixing-point masking, total masking, and
      with counseling alone. DESIGN: Forty-eight tinnitus patients were randomly
      assigned to one of three groups: counseling, counseling plus bilateral noise
      generators set to completely mask the tinnitus, or counseling plus bilateral
      noise generators with a focus on the mixing point (partial masking just below
      total masking). A picture-based counseling protocol was used to assist in
      providing similar counseling among all three groups. The Tinnitus Handicap
      Questionnaire was administered before and after about 12 months of treatment.
      RESULTS: After 12 months, in the counseling group, three of 18 patients benefited
      significantly, in the mixing-point group, six of 19 patients benefited, and in
      the total masking group, four of 11 patients benefited from the treatment. The
      average decrease in the questionnaire was 16.7% for the counseling group, 31.6%
      for the retraining group, and 36.4% for the total masking group. No significant
      average differences among groups were observed. CONCLUSIONS: One premise of
      retraining therapy is incorrect; a focus on mixing-point masking is not required
      for habituation.

PMID- 22609544
TI  - Innovation fund supports video game to help stroke patients regain movement.

PMID- 22609542
TI  - Clinical significance of ankle systolic blood pressure following exercise in
      assessing calf muscle tissue ischemia in peripheral artery disease.
AB  - Our primary objective assessed whether a decline in ankle systolic blood pressure
      (SBP) to less than 50 mm Hg after treadmill exercise is associated with lower
      extremity ischemia, as measured by calf muscle hemoglobin oxygen saturation
      (StO(2)). Eighty-four patients with peripheral artery disease (PAD) completed a
      treadmill test. Ankle SBP <50 mm Hg following exercise was observed in only 49%
      (group 1), whereas 51% had ankle SBP >=50 mm Hg (group 2). No group differences
      were observed for the decline in calf muscle StO(2) to a minimum value (group 1:
      18 +/- 21%, group 2: 20 +/- 20%; P = .60) and for the time to reach minimum
      StO(2) (group 1: 224 +/- 251 seconds, group 2: 284 +/- 283 seconds; P = .30).
      Requirement of ankle SBP to decrease below 50 mm Hg after exercise has little
      clinical significance for assessing ischemia in calf muscle of patients with PAD
      limited by intermittent claudication.

PMID- 22609543
TI  - Ldb1 regulates carbonic anhydrase 1 during erythroid differentiation.
AB  - Carbonic anhydrase 1 (Car1), an early specific marker of the erythroid
      differentiation, has been used to distinguish fetal and adult erythroid cells
      since its production closely follows the gamma- to beta-globin transition, but
      the molecular mechanism underlying transcriptional regulation of Car1 is unclear.
      Here, we show that Car1 mRNA decreases significantly when erythroid
      differentiation is induced in MEL cells. The Ldb1 protein complex including
      GATA1/SCL/LMO2 binds to the Car1 promoter in uninduced cells and reduced
      enrichment of the complex during differentiation correlates with loss of Car1
      expression. Knockdown of Ldb1 results in a reduction of Ser2 phosphorylated RNA
      Pol II and Cdk9 at the Car1 promoter region, suggesting that Ldb1 is required for
      recruitment of Pol II as well as the transcription regulator P-TEFb to enhance
      elongation of Car1 transcripts. Taken together, these data show that Ldb1 forms a
      regulatory complex to maintain Car1 expression in erythroid cells.

PMID- 22609541
TI  - FXR signaling in the enterohepatic system.
AB  - Enterohepatic circulation serves to capture bile acids and other steroid
      metabolites produced in the liver and secreted to the intestine, for reabsorption
      back into the circulation and reuptake to the liver. This process is under tight
      regulation by nuclear receptor signaling. Bile acids, produced from cholesterol,
      can alter gene expression in the liver and small intestine via activating the
      nuclear receptors farnesoid X receptor (FXR; NR1H4), pregnane X receptor (PXR;
      NR1I2), vitamin D receptor (VDR; NR1I1), G protein coupled receptor TGR5, and
      other cell signaling pathways (JNK1/2, AKT and ERK1/2). Among these controls, FXR
      is known to be a major bile acid-responsive ligand-activated transcription factor
      and a crucial control element for maintaining bile acid homeostasis. FXR has a
      high affinity for several major endogenous bile acids, notably cholic acid,
      deoxycholic acid, chenodeoxycholic acid, and lithocholic acid. By responding to
      excess bile acids, FXR is a bridge between the liver and small intestine to
      control bile acid levels and regulate bile acid synthesis and enterohepatic flow.
      FXR is highly expressed in the liver and gut, relative to other tissues, and
      contributes to the maintenance of cholesterol/bile acid homeostasis by regulating
      a variety of metabolic enzymes and transporters. FXR activation also affects
      lipid and glucose metabolism, and can influence drug metabolism.

PMID- 22609545
TI  - Patient who received liver after social media campaign reports success.

PMID- 22609546
TI  - Canadian MPs dismiss findings that food policies are leading to hunger and
      obesity.

PMID- 22609547
TI  - Impact of road networks on the distribution of dengue fever cases in Trinidad,
      West Indies.
AB  - This study examined the impact of road networks on the distribution of dengue
      fever cases in Trinidad, West Indies. All confirmed cases of dengue hemorrhagic
      fever (DHF) observed during 1998 were georeferenced and spatially located on a
      road map of Trinidad using Geographic Information Systems software. A new digital
      geographic layer representing these cases was created and the distances from
      these cases to the nearest classified road category (5 classifications based on a
      functional utility system) were examined. The distance from each spatially
      located DHF case to the nearest road in each of the 5 road subsets was determined
      and then subjected to an ANOVA and t-test to determine levels of association
      between minor road networks (especially 3rd and 4th class roads) and DHF cases
      and found DHF cases were located away from forests, especially 5th class roads).
      The frequency of DHF cases to different road classes was: 0% (1st class roads),
      7% (2nd class roads), 32% (3rd class roads), 57% (4th class roads) and 4% (5th
      class road). The data clearly demonstrated that both class 3 and class 4 roads
      account for 89% of nearby dengue cases. These results represent the first
      evidence of dengue cases being found restricted between forested areas and major
      highways and would be useful when planning and implementing control strategies
      for dengue and Aedes aegypti mosquitoes.

PMID- 22609548
TI  - Real-time PCR strategy for parasite quantification in blood and tissue samples of
      experimental Trypanosoma cruzi infection.
AB  - The lack of an accurate diagnosis has been a serious obstacle to the advancement
      of the anti-Trypanosoma cruzi chemotherapy and long-term infection can result in
      different health risks to human. PCRs are alternative methods, more sensitive
      than conventional parasitological techniques, which due to their low
      sensitivities are considered unsuitable for these purposes. The aim of this study
      was to investigate a sensitive diagnostic strategy to quantify blood and cardiac
      tissues parasites based on real-time PCR tools during acute and chronic phases of
      murine Chagas disease, as well as to monitor the evolution of infection in those
      mice under specific treatment. In parallel, fresh blood examination,
      immunological analysis and quantification of cardiac inflammation were also
      performed to confront and improve real-time PCR data. Similar profiles of
      parasitemia curves were observed in both quantification techniques during the
      acute phase of the infection. In contrast, parasites could be quantified only by
      real-time PCR at 60 and 120 days of infection. In cardiac tissue, real-time PCR
      detected T. cruzi DNA in 100% of infected mice, and using this tool a significant
      Pearson correlation between parasite load in peripheral blood and in cardiac
      tissue during acute and chronic phases was observed. Levels of serum CCL2, CCL5
      and nitric oxide were coincident with parasite load but focal and diffuse
      mononuclear infiltrates was observed, even with significant (p<0.05) reduction of
      parasitism after 60 days of infection. Later, this methodology was used to
      monitor the evolution of infection in animals treated with itraconazole (Itz).
      Itz-treatment induced a reduction of parasite load in both blood and cardiac
      muscle at the treatment period, but after the end of chemotherapy an increase of
      parasitism was detected. Interestingly, inflammatory mediators levels and heart
      inflammation intensity had similar evolution to the parasite load, in the group
      of animals treated. Taken together, our data show that real-time PCR strategy
      used was suitable for studies of murine T. cruzi infection and may prove useful
      in investigations involving experimental chemotherapy of the disease and the
      benefits of treatment in relation to parasitism and inflammatory response.

PMID- 22609549
TI  - Insulin/IGF signaling drives cell proliferation in part via Yorkie/YAP.
AB  - The insulin/IGF signaling (IIS) pathway is a potent inducer of cell proliferation
      in normal development and in cancer. The mechanism by which this occurs, however,
      is not completely understood. The Hippo signaling pathway regulates cell
      proliferation via the transcriptional co-activator Yorkie/YAP, however the
      signaling inputs regulating Hippo activity are not fully elucidated. Here we
      present evidence linking these two conserved, oncogenic pathways in Drosophila
      and in mammalian cells. We find that activation of IIS and of Yorkie signaling
      correlate positively in hepatocellular carcinoma. We show that IIS activates
      Yorkie in vivo, and that Yorkie plays an important role in the ability of IIS to
      drive cell proliferation. Interestingly, we also find the converse--that Yorkie
      signaling activates components of the insulin/TOR pathway. In sum, this crosstalk
      between IIS and Yorkie leads to coordinated regulation of these two oncogenic
      pathways.

PMID- 22609551
TI  - The smooth muscle microRNA miR-145 regulates gut epithelial development via a
      paracrine mechanism.
AB  - MicroRNAs are potent modulators of cellular differentiation. miR-145 is expressed
      in, and promotes the differentiation of vascular and visceral smooth muscle cells
      (SMCs). Interestingly, we have observed that miR-145 also promotes
      differentiation of the gut epithelium in the developing zebrafish, a cell type
      where it is not expressed. Here we identify that a paracrine pathway involving
      the morphogens Sonic hedgehog (Shh) in epithelium and bone morphogenic protein 4
      (Bmp4) in SMCs is modulated by miR-145. We show that expression of miR-145 in
      visceral SMCs normally represses the expression of the morphogen bmp4, as loss of
      miR-145 leads to upregulation of bmp4 in SMCs. We show that bmp4 in turn controls
      expression of Shh in the visceral epithelium. Conversely, in miR-145 morphants
      where bmp4 expression is increased, expression of sonic hedgehog a (shha) is
      strongly increased in gut epithelium. We show that expression of bmp4 is
      modulated by the miR-145 direct target gata6 but not a second potential direct
      target, klf5a. Thus although miR-145 is a tissue-restricted microRNA, it plays an
      essential role in promoting the patterning of both gut layers during gut
      development via a paracrine mechanism.

PMID- 22609550
TI  - BMP receptor-activated Smads confer diverse functions during the development of
      the dorsal spinal cord.
AB  - Bone Morphogenetic Proteins (BMPs) have multiple activities in the developing
      spinal cord: they specify the identity of the dorsal-most neuronal populations
      and then direct the trajectories of dorsal interneuron (dI) 1 commissural axons.
      How are these activities decoded by dorsal neurons to result in different
      cellular outcomes? Our previous studies have shown that the diverse functions of
      the BMPs are mediated by the canonical family of BMP receptors and then regulated
      by specific inhibitory (I) Smads, which block the activity of a complex of Smad
      second messengers. However, the extent to which this complex translates the
      different activities of the BMPs in the spinal cord has remained unresolved.
      Here, we demonstrate that the receptor-activated (R) Smads, Smad1 and Smad5 play
      distinct roles mediating the abilities of the BMPs to direct cell fate
      specification and axon outgrowth. Smad1 and Smad5 occupy spatially distinct
      compartments within the spinal cord, with Smad5 primarily associated with neural
      progenitors and Smad1 with differentiated neurons. Consistent with this
      expression profile, loss of function experiments in mouse embryos reveal that
      Smad5 is required for the acquisition of dorsal spinal neuron identities whereas
      Smad1 is critical for the regulation of dI1 axon outgrowth. Thus the R-Smads,
      like the I-Smads, have discrete roles mediating BMP-dependent cellular processes
      during spinal interneuron development.

PMID- 22609552
TI  - Scube activity is necessary for Hedgehog signal transduction in vivo.
AB  - The Hedgehog (HH) signaling pathway is a central regulator of embryonic
      development, controlling the pattern and proliferation of a wide variety of
      organs. Previous studies have implicated the secreted protein, Scube2, in HH
      signal transduction in the zebrafish embryo (Hollway et al., 2006; Kawakami et
      al., 2005; Woods and Talbot, 2005) although the nature of the molecular function
      of Scube2 in this process has remained undefined. This analysis has been
      compounded by the fact that removal of Scube2 activity in the zebrafish embryo
      leads to only subtle defects in HH signal transduction in vivo (Barresi et al.,
      2000; Hollway et al., 2006; Ochi and Westerfield, 2007; van Eeden et al., 1996;
      Wolff et al., 2003). Here we present the discovery of two additional scube genes
      in zebrafish, scube1 and scube3, and demonstrate their roles in facilitating HH
      signal transduction. Knocking down the function of all three scube genes
      simultaneously phenocopies a complete loss of HH signal transduction in the
      embryo, revealing that Scube signaling is essential for HH signal transduction in
      vivo. We further define the molecular role of scube2 in HH signaling.

PMID- 22609553
TI  - Delay of polarization event increases the number of Cdx2-positive blastomeres in
      mouse embryo.
AB  - During preimplantation mouse embryo development expression of Cdx2 is induced in
      outer cells, which are the trophectoderm (TE) precursors. The mechanism of Cdx2
      upregulation in these cells remains unclear. However, it has been suggested that
      the cell position and polarization may play a crucial role in this process. In
      order to elucidate the role of these two parameters in the formation of TE we
      analyzed the expression pattern of Cdx2 in the embryos in which either the
      position of cells and the time of polarization or only the position of cells was
      experimentally disrupted. Such embryos developed from the blastomeres that were
      isolated from 8-cell embryos either before or after the compaction, i.e. before
      or after the cell polarization took place. We found that in the embryos developed
      from polar blastomeres originated from the 8-cell compacted embryo, the
      experimentally imposed outer position was not sufficient to induce the Cdx2 in
      these blastomeres which in the intact embryo would form the inner cells. However,
      when the polarization at the 8-cell stage was disrupted, the embryos developed
      from such an unpolarized blastomeres showed the increased number of cells
      expressing Cdx2. We found that in such experimentally obtained embryos the
      polarization was delayed until the 16-cell stage. These results suggest that the
      main factor responsible for upregulation of Cdx2 expression in outer blastomeres,
      i.e. TE precursors, is their polarity.

PMID- 22609555
TI  - Surface plasmon resonance detection of E. coli and methicillin-resistant S.
      aureus using bacteriophages.
AB  - Early diagnosis and appropriate treatment of Escherichia coli (E. coli) O157:H7
      and methicillin-resistant Staphylococcus aureus (MRSA) are key elements in
      preventing resultant life-threatening illnesses, such as hemorrhagic colitis,
      hemolytic uremic syndrome, and septicemia. In this report, we describe the use of
      surface plasmon resonance (SPR) for the biodetection of pathogenic bacteria,
      using bacteriophages as the recognition elements. T4 bacteriophages were used to
      detect E. coli, while a novel, highly specific phage was used to detect MRSA. We
      found that the system permits label-free, real-time, specific, rapid and cost
      effective detection of pathogens, for concentrations of 10(3) colony forming
      units/milliliter, in less than 20 min. This system promises to become a
      diagnostic tool for bacteria that cause major public concern for food safety,
      bioterrorism, and nosocomial infections.

PMID- 22609554
TI  - Comparison of the direct electrochemistry of glucose oxidase immobilized on the
      surface of Au, CdS and ZnS nanostructures.
AB  - A comparison of the electrochemical and photoelectrochemical behaviors of three
      biosensors, based on the use of Au, CdS, and ZnS nanoparticles-glucose oxidase
      (GOD) system, is discussed. All the nanoparticles were electrodeposited onto the
      indium tin oxide (ITO) thin film coated glass surface. GOD was then immobilized
      on the nanoparticles-modified electrodes surface with the sol-gel technique. The
      deposited nanoparticles on ITO electrodes were characterized by scanning electron
      microscopy, UV-vis spectroscopy and electrochemical impedance spectra. The direct
      electrochemistry of GOD, analytical performance of glucose calibration curves and
      the kinetic parameters of the enzyme reaction were compared for all the
      electrochemical biosensors. Furthermore, the current response of the quantum dots
      GOD system biosensor can be increased after illumination. The electrochemical and
      photoelectrochemical biosensors based on ZnS nanostructures exhibited higher
      sensitivity than that of Au or CdS nanostructures. Considering ZnS is nontoxic to
      human and environment, the results suggest that ZnS nanoparticles-GOD system
      seems to be a promising platform for fabrication of novel electrochemical and
      photoelectrochemical biosensors.

PMID- 22609556
TI  - Flexible glucose sensor using CVD-grown graphene-based field effect transistor.
AB  - A flexible glucose sensor using a CVD-grown graphene-based field-effect
      transistor (FET) is demonstrated. The CVD-grown graphene was functionalized with
      linker molecules in order to immobilize the enzymes that induce the catalytic
      response of glucose. Polyethylene terephthalate (PET) was employed as the
      substrate material to realize a flexible sensor. The fabricated graphene-based
      FET sensor showed ambipolar transfer characteristics. Through measurements of the
      Dirac point shift and differential drain-source current, the fabricated FET
      sensor could detect glucose levels in the range of 3.3-10.9 mM, which mostly
      covers the reference range of medical examination or screen test for diabetes
      diagnostic. This CVD-grown graphene-based FET sensor, which provides excellent
      fitting to a model curve even when deformed, high resolution, and continuous real
      time monitoring, holds great promise, especially for portable, wearable, and
      implantable glucose level monitoring applications.

PMID- 22609557
TI  - Mechanical metamaterials with negative compressibility transitions.
AB  - When tensioned, ordinary materials expand along the direction of the applied
      force. Here, we explore network concepts to design metamaterials exhibiting
      negative compressibility transitions, during which a material undergoes
      contraction when tensioned (or expansion when pressured). Continuous contraction
      of a material in the same direction of an applied tension, and in response to
      this tension, is inherently unstable. The conceptually similar effect we
      demonstrate can be achieved, however, through destabilizations of (meta)stable
      equilibria of the constituents. These destabilizations give rise to a stress
      induced solid-solid phase transition associated with a twisted hysteresis curve
      for the stress-strain relationship. The strain-driven counterpart of negative
      compressibility transitions is a force amplification phenomenon, where an
      increase in deformation induces a discontinuous increase in response force. We
      suggest that the proposed materials could be useful for the design of actuators,
      force amplifiers, micromechanical controls, and protective devices.

PMID- 22609558
TI  - Quantum phase transitions: Emergent inhomogeneity.

PMID- 22609559
TI  - Electrical control of the superconducting-to-insulating transition in graphene
      metal hybrids.
AB  - Graphene is a sturdy and chemically inert material exhibiting an exposed two
      dimensional electron gas of high mobility. These combined properties enable the
      design of graphene composites, based either on covalent or non-covalent coupling
      of adsorbates, or on stacked and multilayered heterostructures. These systems
      have shown tunable electronic properties such as bandgap engineering, reversible
      metal-insulating transition or supramolecular spintronics. Tunable
      superconductivity is expected as well, but experimental realization is lacking.
      Here, we show experiments based on metal-graphene hybrid composites, enabling the
      tunable proximity coupling of an array of superconducting nanoparticles of tin
      onto a macroscopic graphene sheet. This material allows full electrical control
      of the superconductivity down to a strongly insulating state at low temperature.
      The observed gate control of superconductivity results from the combination of a
      proximity-induced superconductivity generated by the metallic nanoparticle array
      with the two-dimensional and tunable metallicity of graphene. The resulting
      hybrid material behaves, as a whole, like a granular superconductor showing
      universal transition threshold and localization of Cooper pairs in the insulating
      phase. This experiment sheds light on the emergence of superconductivity in
      inhomogeneous superconductors, and more generally, it demonstrates the potential
      of graphene as a versatile building block for the realization of superconducting
      materials.

PMID- 22609560
TI  - Light scattering by a medium with a spatially modulated optical conductivity: the
      case of graphene.
AB  - We describe light scattering from a graphene sheet having a modulated optical
      conductivity. We show that such modulation enables the excitation of surface
      plasmon polaritons by an electromagnetic wave impinging at normal incidence. The
      resulting surface plasmon polaritons are responsible for a substantial increase
      of electromagnetic radiation absorption by the graphene sheet. The origin of the
      modulation can be due either to a periodic strain field or to adatoms (or
      absorbed molecules) with a modulated adsorption profile.

PMID- 22609562
TI  - Evaluation of collimators' response: round and hexagonal holes in parallel and
      fan beam.
AB  - With regard to the different requirements, various collimators are widely
      employed within nuclear medicine systems in order to evaluate the metabolism of
      organs as well as improve the contrast of images and better diagnosis. In this
      study, Fan Beam (FB) and Parallel Beam (PB) collimators in the shapes of round
      and hexagonal holes have been investigated and compared based on the Geometric
      Efficiency (G), Geometric Resolution (R(c)), Total Resolution (R(t)), FWHM and
      Scatter and Penetration (S + P) components using the Monte Carlo simulation.
      Calculations demonstrated that the G was improved with the increase in the
      distance between point source and collimator face (z). In contrast, the G was
      reduced with an increase in the angle of slant hole. In the FB collimator, the
      R(c) and R(t) were increased when the increase in the hole angle and/or the
      distance. The simulated results indicated in both collimators with the increase
      in z, a) the FWHM was increased as well as the peak of the PSF curve was
      decreased, and b) the S + P amounts decreased, but in the distinct z, the FWHM of
      the FB collimator is better than that of the PB collimator. It is shown that the
      results were in agreement with the ADAC company data. Also, Benchmark for
      measuring ADAC company demonstrated the calculated and simulated amounts of the
      R(c) and R(t) with round and hexagonal holes shapes had maximum and minimum
      average relative differences equal to -7.6% for PB and 1% for FB, respectively.

PMID- 22609561
TI  - Extracellular matrix and cytoskeletal dynamics during branching morphogenesis.
AB  - Branching morphogenesis is a fundamental developmental process which results in
      amplification of epithelial surface area for exchanging molecules in organs
      including the lung, kidney, mammary gland and salivary gland. These complex tree
      like structures are built by iterative rounds of simple routines of epithelial
      morphogenesis, including bud formation, extension, and bifurcation, that require
      constant remodeling of the extracellular matrix (ECM) and the cytoskeleton. In
      this review, we highlight the current understanding of the role of the ECM and
      cytoskeletal dynamics in branching morphogenesis across these different organs.
      The cellular and molecular mechanisms shared during this morphogenetic process
      provide insight into the development of other branching organs.

PMID- 22609563
TI  - Towards experimental manipulation of stochasticity in gene expression.
AB  - For decades, most of molecular biology was driven by the "central dogma" in which
      the phenotype is defined by the genotype following a fully deterministic point of
      view. However, during the last 10 years, a wealth of studies has demonstrated
      that a given genotype can generate multiple phenotypes in identical environmental
      conditions, mainly because of the inherently probabilistic nature of the
      transcription process. It has also been shown that cells can tune this
      variability at the molecular level. Although previously described as a useless
      "noise", stochastic gene expression has now been shown by many authors to be an
      essential part of diverse biological processes. Chromatin dynamics having a
      central role in higher eukaryotes, we decided to investigate its involvement in
      the generation and control of stochasticity in gene expression (SGE). Our
      experiments reveal that the chromatin environment of a gene plays an important
      role in regulating SGE. Indeed, we find that histone acetylation and DNA
      methylation significantly affect SGE, suggesting that cells are able to adjust
      the variability of the expression of their genes through modification of
      chromatin marks. Given that the alteration of chromatin marks is itself subject
      to the expression of chromatin modifiers, our results shed light on a complex
      circular causality with on the one hand, the effect of gene expression on
      chromatin and on the other hand, the influence of the local chromatin environment
      of a gene on the dynamics of its expression.

PMID- 22609564
TI  - Transition probability in cell proliferation, stochasticity in cell
      differentiation, and the restriction point of the cell cycle in one package.
AB  - Clonal cells are known to display stochastically varying interdivision times
      (IMT) and stochastic choices of cell fates. These features are suggested in the
      present paper to stem from discrete transitions of genes between different modes
      of their engagement in transcription. These transitions are explained by
      stochastic events of assembly/disassembly of huge ensembles of transcription
      factors needed to built-up gene-specific transcription preinitiation complexes
      (PIC). The time required to assemble a PIC at a gene promoter by random
      collisions of numerous proteins may be long enough to be comparable with the cell
      cycle. Independently published findings are reviewed to show that active genes
      may display discontinuous patterns of transcriptional output consistent with
      stochastically varying periods of PIC presence or absence at their promoters, and
      that these periods may reach several hours. This timescale matches the time
      needed for synchronised clonal cells to pass the restriction point (RP) of the
      cell cycle. RP is suggested to correspond to cell state where cell fate is
      determined by competing discrete transcriptional events. Cell fate choice depends
      on the event that, by chance, has outpaced other events able to commit the cell
      to alternative fates. Simple modelling based on these premises is consistent with
      general features of cell kinetics, including RP passage dependance on mitogenic
      stimulation, IMT distributions conformance to exponentially modified Gaussian,
      the limited proliferative potential of untransformed cells, relationships between
      changes in cell proliferation and differentiation, and bimodal distributions of
      cells over expression levels of genes involved in stem cell differentiation.

PMID- 22609565
TI  - Structural and spectroscopic study of Al(III)-3-hydroxyflavone complex:
      determination of the stability constants in water-methanol mixtures.
AB  - Stoichiometry and apparent stability constant (K(C)) of the complex formed
      between Al(III) and 3-hydroxyflavone were determined in methanol and water
      methanol mixtures (% water w/w: 3.11; 6.15; 10.4; 15.2; 19.9 and 25.3) by UV-vis
      spectroscopy at 25.0 degrees C and constant ionic strength (0.05 M, sodium
      chloride). Stoichiometry of the complex (1:2, metal:ligand) is not modified with
      an increase in water percentage in the analyzed interval. The value of K(C) in
      methanol is greater than in the binary solutions. The effects of changing solvent
      composition on K(C) data were explained by linear solvation free energy
      relationships using the solvatochromic parameter of Kamlet and Taft (alpha, beta
      and pi(*)). Multiple linear regression analysis indicates that the hydrogen bond
      donating ability (alpha) of the solvent and non-specific interactions (pi(*))
      play an important role in the degree of occurrence of the reaction. The effect of
      temperature on K(C) was also analyzed by assessing standard entropy and enthalpy
      variations of the reaction in methanol. Finally, the structure of the complex was
      investigated using FTIR spectroscopy and DFT calculations. The ligand exhibits
      small structural changes upon complexation, localized on the chelating site. The
      calculated vibrational frequencies of the complex were successfully compared
      against the experimental values.

PMID- 22609566
TI  - Synthesis, characterization and color performance of novel Co2+-doped
      alumina/titania nanoceramic pigments.
AB  - Blue-green nanoceramic pigments from Co(2+)-doped alumina-titania (xCo(2+)
      Al(2)O(3)/TiO(2)) have been synthesized by alkoxide sol-gel route from a mixture
      of titania and boehmite sols that derived from titanium isopropoxide and aluminum
      nitrate precursors. The composition of the alumina/titania (AT) matrix is 3:1M
      ratio. A series of xCo(2+):3TiO(2):1Al(2)O(3) mixed oxides with different Co(2+)
      dopant ion concentration has been prepared. The molar ratio of the Co(2+)-dopant
      ion in the Al(2)O(3)/TiO(2) matrix is from x=0 to 0.5M ratio relative to the
      titania composition. Characterizations of Co(2+)-doped alumina/titania
      nanocomposites are carried out using reflectance spectroscopy, transmission
      electron microscope (TEM), scanning electron microscopy (SEM-EDS), thermo
      gravimetric analysis (TGA) and X-ray diffractometer (XRD). The experimental
      results demonstrated that the prepared Co(2+)-doped alumina-titania
      nanocomposites fulfill the current technological requirements for ceramic pigment
      applications that exhibit a high physico-chemical and thermal stabilities at high
      firing temperatures.

PMID- 22609567
TI  - Theoretical studies of g factors for V3+ in ZnS, ZnSe and ZnTe crystals.
AB  - In this paper, complete high-order perturbation formulas are established based
      not only on the contributions of the spin-orbit coupling effect of the central
      ion and the ligands, but also on that of the charge-transfer levels. The electron
      paramagnetic resonance g-factors of ZnS:V(3+), ZnSe:V(3+), and ZnTe:V(3+)
      crystals are calculated from the formulas. The calculations of the EPR g-factors
      agree well with the experimental values. The contribution rate of the charge
      transfer levels (|Deltag(T)/Deltag(F)|) are 20.16%, 24.86%, and 24.87% for
      ZnS:V(3+), ZnSe:V(3+), and ZnTe:V(3+) crystals, respectively.

PMID- 22609568
TI  - Determining long-range chromatin interactions for selected genomic sites using 4C
      seq technology: from fixation to computation.
AB  - Chromosome Conformation Capture (3C) and 3C-based technologies are constantly
      evolving in order to probe nuclear organization with higher depth and resolution.
      One such method is 4C-technology that allows the investigation of the nuclear
      environment of a locus of choice. The use of Illumina next generation sequencing
      as a detection platform for the analysis of 4C data has further improved the
      sensitivity and resolution of this method. Here we provide a step-by-step
      protocol for 4C-seq, describing the procedure from the initial template
      preparation until the final data analysis, interchanged with background
      information and considerations.

PMID- 22609569
TI  - Rapid eye movement sleep deprivation modulates synapsinI expression in rat brain.
AB  - Rapid eye movement sleep (REMS) deprivation (REMSD) has been reported to elevate
      neurotransmitter level in the brain; however, intracellular mechanism of its
      increased release was not studied. Phosphorylation of synapsinI, a synaptic
      vesicle-associated protein, is involved in the regulation of neurotransmitter
      release. In this study, rats were REMS deprived by classical flowerpot method;
      free moving control (FMC), large platform control (LPC) and recovery control
      (REC) was carried out. In another set REMS deprived rats were intraperitoneally
      (i.p.) injected with alpha1-adrenoceptor antagonist, prazosin (PRZ). Effects of
      REMSD on Na-K ATPase activity and on the total synapsinI as well as
      phosphorylated synapsinI levels were estimated in synaptosomes prepared from
      whole brain. It was observed that REMSD significantly increased synaptosomal Na-K
      ATPase activity, which was prevented by PRZ. Western blotting of the same samples
      by anti-synapsinI and anti-synapsinI-phosphoSer603 showed that REMSD increased
      both the total as well as phospho-form of synapsinI as compared to respective
      levels in FMC and LPC samples. These findings suggest a functional link between
      REMSD and synaptic vesicular mobilization at the presynaptic terminal, a process
      that is essential for neurotransmitter release. The findings help explaining the
      intracellular mechanism of elevated neurotransmitter release associated to REMSD.

PMID- 22609571
TI  - Functional roles of endogenous D-serine in the chronic pain-induced plasticity of
      NMDAR-mediated synaptic transmission in the central amygdala of mice.
AB  - The amygdala is implicated in chronic pain-induced emotional changes. Chronic
      pain induces plastic changes of the N-methyl-d-aspartate receptor (NMDAR)
      functions in the brain including the amygdala. d-Serine is synthesized
      endogenously by serine racemase and modulates NMDAR-mediated synaptic
      transmission as a coagonist of glycine binding site. To clarify the functional
      roles of endogenous d-serine in chronic pain-induced plasticity of NMDAR mediated
      synaptic transmission, we investigated the NMDAR-mediated excitatory synaptic
      current (EPSC) of neurons in the latero-capsular division of the central amygdala
      (CeLC) using brain slices from serine racemase knockout (SR-KO) mice with chronic
      pain induced by monoarthritis. The decay time of NMDAR-mediated EPSC was
      significantly elongated by monoarthritis in wild type (WT) mice, but not in SR-KO
      mice. The d-serine application-induced increase of NMDAR-mediated EPSC was
      significantly facilitated by monoarthritis in WT mice, but not in SR-KO mice.
      These results suggest that endogenous d-serine facilitates chronic pain-induced
      plastic changes of NMDAR mediated synaptic transmission in CeLC.

PMID- 22609570
TI  - Insulin-like growth factor 1 (IGF1) and its active peptide (1-3)IGF1 enhance the
      expression of synaptic markers in neuronal circuits through different cellular
      mechanisms.
AB  - Insulin-like growth factor-1 (IGF1) and its active peptide (1-3)IGF1 modulate
      brain growth and plasticity and are candidate molecules for treatment of brain
      disorders. IGF1 N-terminal portion is naturally cleaved to generate the tri
      peptide (1-3)IGF1 (glycine-praline-glutamate). IGF1 and (1-3)IGF have been
      proposed as treatment for neuropathologies, yet their effect on nerve cells has
      not been directly compared. In this study we examine the effects of IGF1 and (1
      3)IGF1 in primary cortical cultures and measure the expression levels of markers
      for intracellular pathways and synaptic function. We find that both treatments
      activate the IGF1 receptor and enhance the expression of synaptic markers,
      however, they activate different intracellular pathways. Furthermore, (1-3)IGF1
      administration increases the expression of endogenous IGF1, suggesting a direct
      interaction between the two molecules. The results show that the two molecules
      increase the expression of synaptic proteins through activating different
      cellular mechanisms.

PMID- 22609572
TI  - Formulation design and in vivo antimalarial evaluation of lipid-based drug
      delivery systems for oral delivery of beta-arteether.
AB  - beta-Arteether, an effective artemisinin derivative, is used in the treatment of
      malaria but available only as an intramuscular injection. The objective of this
      work was to develop lipid-based formulations for oral administration of beta
      arteether. Self-emulsifying drug delivery systems (SEDDSs) of low cost and with
      accessible excipients (groundnut or sesame oil, Maisine 35-1, Tween 80 or
      Cremophor EL, and absolute ethanol) were formulated. In 250 ml of simulated
      gastric medium, 1g of these SEDDS solubilized the daily dose of beta-arteether
      and formed lipid droplets of average size 80-250 nm. No toxicity against Caco-2
      intestinal cells was observed. Using a mouse model, the efficacy of these
      arteether lipid formulations against Plasmodium berghei was evaluated. A daily
      dose of 24 mg/kg for 4 days led to complete cure for more than 45 days in 100% of
      treated mice and had an antimalarial efficacy comparable to that of an
      intramuscular oily solution of arteether and significantly higher than that of an
      oily solution of beta-arteether given orally at the same dose. In conclusion,
      lipid-based drug delivery systems constitute a promising approach for the oral
      administration of beta-arteether.

PMID- 22609573
TI  - Emotional reactivity and awareness of task performance in Alzheimer's disease.
AB  - Lack of awareness about performance in tasks is a common feature of Alzheimer's
      disease. Nevertheless, clinical anecdotes have suggested that patients may show
      emotional or behavioural responses to the experience of failure despite reporting
      limited awareness, an aspect which has been little explored experimentally. The
      current study investigated emotional reactions to success or failure in tasks
      despite unawareness of performance in Alzheimer's disease. For this purpose,
      novel computerised tasks which expose participants to systematic success or
      failure were used in a group of Alzheimer's disease patients (n=23) and age
      matched controls (n=21). Two experiments, the first with reaction time tasks and
      the second with memory tasks, were carried out, and in each experiment two
      parallel tasks were used, one in a success condition and one in a failure
      condition. Awareness of performance was measured comparing participant
      estimations of performance with actual performance. Emotional reactivity was
      assessed with a self-report questionnaire and rating of filmed facial
      expressions. In both experiments the results indicated that, relative to
      controls, Alzheimer's disease patients exhibited impaired awareness of
      performance, but comparable differential reactivity to failure relative to
      success tasks, both in terms of self-report and facial expressions. This suggests
      that affective valence of failure experience is processed despite unawareness of
      task performance, which might indicate implicit processing of information in
      neural pathways bypassing awareness.

PMID- 22609575
TI  - Magno and parvo stimuli affect illusory directional hearing in normal and
      dyslexic readers.
AB  - In an experimental paradigm adapted from Hari (1995), forty observers listened
      via headphones to 8 binaural clicks: 4 left-ear leading followed by 4 right-ear
      leading with either 38 or 140 ms interstimulus intervals (ISIs). Concurrently,
      they viewed either foveal or peripheral visual stimuli designed to activate
      either the parvocellular or magnocellular pathway. They then reported the
      perceived location of each click-pair. Our results replicated Hari's finding that
      observers mistake the perceived location of short ISI click-pairs more often than
      long. That is, when ISIs were short, the sounds seemed to play across the inside
      of the head in a phenomenon called illusory directional hearing. However, when
      click-pairs were accompanied by peripheral visual stimuli that activated the
      magnocellular pathway, observers were more accurate than when there were no
      visual stimuli. Conversely, parvocellular-activating foveal visual stimuli
      produced more illusory hearing than when there were no visual stimuli. These
      findings suggest that activating the slow sustained parvocellular system may
      result in a longer processing window. Thirty dyslexic observers who repeated the
      experimental paradigm had an even longer processing window than control observers
      indicating that dyslexics may have a magnocellular system deficit.

PMID- 22609574
TI  - Intact implicit verbal relational memory in medial temporal lobe amnesia.
AB  - To elucidate the role of the hippocampus in unaware relational memory, the
      present study examined the performance of amnesic patients with medial temporal
      lobe (MTL) lesions on a cued category-exemplar generation task. In contrast to a
      prior study in which amnesic patients showed impaired performance (Verfaellie et
      al., Cognitive, Affective, and Behavioral Neuroscience, 2006, 6, 91-101), the
      current study employed a task that required active processing of the context word
      at test. In this version of the task, amnesic patients, like control
      participants, showed enhanced category exemplar priming when the context word
      associated with the target at study was reinstated at test. The finding of intact
      implicit memory for novel associations following hippocampal lesions in a task
      that requires flexible use of retrieval cues is inconsistent with a relational
      memory view that suggests that the hippocampus is critical for all forms of
      relational memory, regardless of awareness. Instead, it suggests that unaware
      memory for within-domain associations does not require MTL mediation.

PMID- 22609576
TI  - Acetylcholinesterase inhibitors reduce spreading activation in dementia.
AB  - Alzheimer's disease is associated with degeneration of the cholinergic system,
      which affects memory and attention functioning. Acetylcholinesterase inhibitors
      (AChEI) have been found to increase attention and given this effect might reduce
      spreading activation of memory nodes in lexical/semantic networks. We sought to
      determine whether this effect of AChEIs existed in a group of patients with
      dementia. A mixed sample of 34 patients with dementia (17 taking AChEIs and 17
      not taking these medications) were administered the Controlled Oral Word
      Association Test and the Animal Naming Test. The average word frequency for their
      responses was obtained and used as a measure of spreading activation. Patients
      taking AChEIs had a significantly higher average word frequency for the COWAT as
      compared to those not taking AChEIs. No difference was found for the average word
      frequencies for the AN test. Administration of AChEIs appears to reduce spreading
      activation, possibly due to cholinergic innervations of the frontal cortex.

PMID- 22609577
TI  - Auditory skills and brain morphology predict individual differences in adaptation
      to degraded speech.
AB  - Noise-vocoded speech is a spectrally highly degraded signal, but it preserves the
      temporal envelope of speech. Listeners vary considerably in their ability to
      adapt to this degraded speech signal. Here, we hypothesised that individual
      differences in adaptation to vocoded speech should be predictable by non-speech
      auditory, cognitive, and neuroanatomical factors. We tested 18 normal-hearing
      participants in a short-term vocoded speech-learning paradigm (listening to 100 4
      band-vocoded sentences). Non-speech auditory skills were assessed using amplitude
      modulation (AM) rate discrimination, where modulation rates were centred on the
      speech-relevant rate of 4 Hz. Working memory capacities were evaluated (digit
      span and nonword repetition), and structural MRI scans were examined for
      anatomical predictors of vocoded speech learning using voxel-based morphometry.
      Listeners who learned faster to understand degraded speech also showed smaller
      thresholds in the AM discrimination task. This ability to adjust to degraded
      speech is furthermore reflected anatomically in increased grey matter volume in
      an area of the left thalamus (pulvinar) that is strongly connected to the
      auditory and prefrontal cortices. Thus, individual non-speech auditory skills and
      left thalamus grey matter volume can predict how quickly a listener adapts to
      degraded speech.

PMID- 22609578
TI  - Motor familiarity: brain activation when watching kinematic displays of one's own
      movements.
AB  - The perception of action is influenced by the observer's familiarity with its
      movement. However, how does motor familiarity with own movement patterns modulate
      the visual perception of action effects? Cortical activation was examined with
      fMRI while 20 observers were watching videotaped point-light displays of markers
      on the shoulders, the right elbow, and wrist of an opposing table tennis player.
      The racket and ball were not displayed. Participants were asked to predict the
      invisible effect of the stroke, that is, the ball flight direction. Different
      table tennis models were used without the observers knowing and being informed in
      advance that some of the presented videos displayed their own movements from
      earlier training sessions. Prediction had to be made irrespective of the identity
      of the player represented by the four moving markers. Results showed that
      participants performed better when observing their "own" strokes. Using a region
      of-interest approach, fMRI data showed that observing own videos was accompanied
      by stronger activation (compared to other videos) in the left angular gyrus of
      the inferior parietal lobe and the anterior rostral medial frontal cortex. Other
      videos elicited stronger activation than own videos in the left intraparietal
      sulcus and right supramarginal gyrus. We suggest that during action observation
      of motorically familiar movements, the compatibility between the observed action
      and the observers' motor representation is already coded in the parietal angular
      gyrus--in addition to the paracingulate gyrus. The activation in angular gyrus is
      presumably part of an action-specific effect retrieval that accompanies actor
      specific prefrontal processing. The intraparietal sulcus seems to be sensitive to
      incongruence between observed kinematics and internal model representations, and
      this also influences processing in the supramarginal gyrus.

PMID- 22609579
TI  - The neuroscience of group membership.
AB  - The present study aimed to uncover the neural activity associated with specific
      in-group and out-group word related stimuli, to examine the neuroanatomical basis
      of group membership concept representation, and investigate to what extent neural
      processes represent 'in-group' differently from 'out-group'. Participants' brain
      activity was measured with functional MRI while they had to categorize social, in
      group and out-group words and non-social, living and non-living words. The
      results showed that a network of brain regions previously identified as the
      'social brain', including the cortical midline structures, tempo-parietal
      junction and the anterior temporal gyrus showed enhanced activation for social
      words versus non-social words. Crucially, the processing of in-group words
      compared to the out-group words activated a specific network including the
      ventral medial prefrontal and anterior and dorsal cingulate cortex. These regions
      correspond to a neural network previously identified as the 'personal self'. Our
      results suggest that the 'social' and 'personal self' are closely related and
      that we derive our self image from the groups we belong to.

PMID- 22609580
TI  - Abrupt and ramped flicker-defined form shows evidence for a large magnocellular
      impairment in dyslexia.
AB  - Controversy still exists over whether there is a magnocellular deficit associated
      with developmental dyslexia. Here we utilised a magnocellular system-biased
      phantom contour form discrimination task defined by high temporal frequency
      contrast reversals to compare contrast sensitivity in a group of children with
      dyslexia and an age- and nonverbal intelligence-matched control group (9-14
      years). Stimuli were either abruptly presented for 4 refresh frames (34 ms), or
      in two reduced transience conditions had contrast progressively ramped on and off
      over either 4 frames or 10 frames (86 ms). Children in the dyslexia group showed
      increased contrast thresholds compared with the control group in all three
      conditions, and thus strong evidence for a magnocellular deficit. Although the
      absolute size of the differences in threshold scores between control and dyslexic
      groups increased dramatically between the abrupt and the 4 and 10 frame ramped
      onset stimuli, the similar effect size across all tasks, and also the similar
      range of contrast change at the first frame of stimulus presentation across all
      tasks between groups suggests that a similar neural mechanism could provide the
      locus of the apparent magnocellular deficit in children with dyslexia for all
      tasks tested. These results suggest that threshold discrimination of stimuli with
      low contrast and high temporal frequencies designed to target the magnocellular
      system, and has great potential for early screening for children at risk of
      visually derived reading difficulties.

PMID- 22609581
TI  - Synthesis of hollow copper oxide by electrospinning and its application as a
      nonenzymatic hydrogen peroxide sensor.
AB  - Cupric acetate/polyacrylonitrile composite nanofibers were prepared by
      electrospinning and hollow copper oxide (CuO) particles were produced after
      subsequent thermal treatment process. The electrospun hollow CuO particles
      modified carbon paste electrode (CPE) was demonstrated for the first time for
      nonenzymatic hydrogen peroxide (H(2)O(2)) sensor. The structures and morphologies
      of hollow CuO particles were characterized by scanning electron microscopy and X
      ray diffraction spectrum. The assay performance of the modified sensor to
      H(2)O(2) was evaluated by cyclic voltammetry and amperometry, revealing high
      sensitivity (1746.50 MUA mM(-1) cm(-2)), low detection limit (0.022 MUM) and wide
      linear response of determination of H(2)O(2) oxidation in the range of 0.05 MUM
      to 1.00 mM.

PMID- 22609582
TI  - Interaction of chlorhexidine with biomembrane models on glass ionomer by using
      the Langmuir-Blodgett technique.
AB  - The antimicrobial property of chlorhexidine is believed to be associated with its
      interaction of bacterium membrane, which calls for research on the identification
      of membranes sites capable of drug binding. In this study, we investigated the
      interaction of chlorhexidine digluconate, a known agent with bactericidal and
      bacteriostatic activities employed in the treatment of periodontal diseases, with
      bacteria cell model systems by using Langmuir monolayers. The insertion of the
      drug caused the surface pressure-area isotherms for a mixed protein-lipid
      monolayer to be shifted to higher lipid molecular areas, which was the first
      indication of the action of chlorhexidine in the membrane model. Surface infrared
      spectroscopy pointed to intrinsic interactions of the drug with the hydrophobic
      part of the lipid, leading to a disruption of the lipid organization at the
      interface. Also, the secondary structure of the polypeptide model employed in
      this work has been changed, as a consequence of the drug interactions. Such
      change in the lipid-protein models could be confirmed when the membrane was
      transferred to glass ionomer cement as a solid support, which can be considered a
      model for dental surfaces. Therefore, chlorhexidine interacts with lipid and
      protein moieties supposed to be present in lipid membranes. This may have
      important implication in understanding how the drug acts on specific sites of the
      bacteria membrane.

PMID- 22609584
TI  - Simple surface treatment using amphiphilic phospholipid polymers to obtain
      wetting and lubricity on polydimethylsiloxane-based substrates.
AB  - Simple surface treatment of polydimethylsiloxane (PDMS) substrates was performed
      using an aqueous-ethanolic solution of amphiphilic phospholipid polymers to
      reduce the hydrophobic and high friction characteristics of PDMS. The
      phospholipid polymers, poly(2-methacryloyloxyethyl phosphorylcholine (MPC)-co-2
      ethylhexyl methacrylate (EHMA)-co-2-(N,N-dimethylamino)ethyl methacrylate) (PMED)
      and poly(MPC-co-EHMA) (PMEH) were synthesized, and the effects of the electric
      charge of the polymer chain on the stability of the attachment to the PDMS
      surface was investigated. The polymers were dissolved in a mixed solvent of
      ethanol and water, and the PDMS samples were treated by a simple dipping method
      using the polymer solution. Pure ethanol as the solvent was ineffective for the
      attachment of the polymers to the PDMS surface. It was considered that the
      hydrophobic interactions and electrostatic attraction forces between the polymer
      chains and the PDMS surface were too weak for efficient interaction in this
      solvent. On the other hand, the surface wettability and lubricity of PDMS could
      be improved by treatment with an aqueous-ethanolic solution of PMED. The static
      contact angle was decreased from 90 degrees  to 20 degrees  by this treatment,
      and the dynamic friction coefficient against a Co-Cr ball was decreased by nearly
      80% compared with that of the untreated PDMS. The hydrophobic interactions and
      electrostatic attraction forces generated by PMED were both essential for the
      stable adsorption of the polymer layer on PDMS. Furthermore, the solubilized
      state of the polymers affected the adsorption of the polymer. We concluded that
      the surface of PDMS could be stably modified using aqueous-ethanolic solutions of
      PMED without the need for pretreatments.

PMID- 22609583
TI  - Adsorption and desorption of doxorubicin on oxidized carbon nanotubes.
AB  - Carbon nanotubes (CNTs) show promise as nano-drug carriers. To develop the CNT
      based drug delivery systems, drug loading and release are two major issues. In
      this study, we systematically evaluated the adsorption and desorption of
      doxorubicin (DOX) on oxidized multi-walled CNTs (O-MWCNTs). Our results indicated
      that O-MWCNTs possessed a huge adsorption capacity for DOX (9.45*10(3) mg/g).
      Although the adsorption process was quite slow, the adsorption capacity kept high
      enough for the therapy while shortening the incubation time to 2h (1.03*10(3)
      mg/g). The desorption of DOX from O-MWCNTs scarcely occurred while incubated in
      buffer solution at both pH 7.4 and pH 5.5, however, the lower pH did benefit the
      desorption. The presence of serum proteins facilitated the desorption of DOX
      significantly, because these proteins bound strongly to O-MWCNTs resulting in the
      partial surface of O-MWNCTs being occupied. Moreover, the adsorption time also
      affected the release of DOX from O-MWCNTs. Shortening the incubation time
      benefited the release of DOX. The implications to the drug loading and
      therapeutics of the CNT-based drug delivery systems are discussed.

PMID- 22609585
TI  - Pluronic-Nanogold hybrids: synthesis and tagging with photosensitizing molecules.
AB  - The design of polymeric-metal hybrid nanocomposites with multiple
      functionalities, i.e. from enabling detection and imaging to assisting diagnosis
      and therapy, is becoming an important research topic in nanomedicine. In this
      work, Pluronic-Nanogold hybrid nanoparticles (Au-PF127) were successfully
      prepared in aqueous solution in a single step reaction using Pluronic F127 block
      copolymer as both reducing and stabilizing agent. The ability of polymer to
      control the nanoparticle formation and stabilization was systematically
      investigated by several characterization techniques: UV-Vis absorption,
      transmission electron microscopy (TEM), dynamic light scattering (DLS) and zeta
      potential measurements. It was found that polymer concentrations higher than
      critical micelle concentration (CMC) provide stable nanoparticles even in high
      molarity NaCl solution. In view of biomedical applications, as prepared Au-PF127
      nanoparticles were modified with Methylene Blue (MB) phenothiazinium based
      photosensitizing drug. Combined surface enhanced Raman scattering (SERS) and
      fluorescence detection of MB embedded within the polymer shell has revealed the
      dual functionality of MB-encoded Pluronic-Nanogold hybrids (Au-PF127-MB) to
      operate under biological conditions as both effective drug carriers and sensitive
      optical probes.

PMID- 22609586
TI  - Enhanced transdermal permeability of estradiol using combination of PLGA
      nanoparticles system and iontophoresis.
AB  - Estradiol is a therapeutic agent for treatment of perimenopausal symptoms and
      osteoporosis. Conventional oral or intravenous administration of estradiol has
      many problems, such as, metabolization in gastrointestinal tract and liver, pain
      by using an injection needle, rapid increase of drug levels in blood and fast
      clearance with unwanted side effects including thrombosis, endometriosis and
      uterus carcinoma. The use of nanocarriers for transdermal delivery has been
      studied because of their ability to deliver therapeutic agents for long time with
      a controlled ratio, escaping from the first pass effect by liver. In this study,
      permeability of estradiol-loaded PLGA nanoparticles through rat skin was studied.
      Higher amount of estradiol was delivered through skin when estradiol was loaded
      in nanoparticles than estradiol was free molecules. Also, iontophoresis was
      applied to enhance the permeability of nanoparticles. When iontophoresis was
      applied, permeability of estradiol-loaded PLGA nanoparticles was much higher than
      that obtained by simple diffusion of them through skin, since they have negative
      surface charges. They were found to penetrate through follicles mainly. Also,
      enhanced permeability effect of estradiol by using nanoparticle system and
      iontophoresis were observed in vivo. The combination of charged nanoparticle
      system with iontophoresis is useful for effective transdermal delivery of
      therapeutic agents.

PMID- 22609588
TI  - Long-term survival and functional maintenance of hepatocytes by using a
      microfabricated cell array.
AB  - We developed a microfabricated cell array of hepatocyte spheroids that showed
      long-term viability and retained the properties of the parent hepatocytes. Fresh
      hepatocytes harvested from 8-week-old Wistar rats were cocultured with feeder
      cells to rapidly form hepatocyte spheroids; these cells retained the spheroidal
      formation for 42 days. We also evaluated the cellular functions of the
      hepatocytes such as albumin secretion and metabolic activity of cytochrome P450
      (CYP). In spheroids in which hepatocytes were cocultured with feeder cells, these
      cellular functions were retained even after 42 days. Therefore, this novel
      coculture will be very useful not only for research on the mechanism and
      treatment of liver diseases but also for early prediction of hepatocyte toxicity
      in the pre-clinical phase of drug development.

PMID- 22609587
TI  - Electrochemical behavior of Azure A/gold nanoclusters modified electrode and its
      application as non-enzymatic hydrogen peroxide sensor.
AB  - A novel non-enzymatic hydrogen peroxide sensor was developed using Azure A/gold
      nanoclusters modified graphite electrode. The method of preparation of Azure
      A/gold nanoclusters was simple and it was characterized by UV-visible
      spectroscopy, field emission scanning electron microscopy (FESEM) and confocal
      Raman microscopy. The electrochemical properties of Azure A/gold nanoclusters
      modified graphite electrode was characterized by cyclic voltammetry. In 0.1M
      H(2)SO(4) the modified electrode showed redox peaks which correspond to the redox
      behavior of gold nanoparticle. In 0.1M PBS the modified electrode exhibited well
      defined redox peaks with the formal potential of -0.253 V which is analogous to
      the redox reaction of Azure A. The results have shown that the gold nanoclusters
      has reduced the formal potential of Azure A and enhanced the current due to the
      fast charge transfer kinetics. Also the modified electrode showed an enhanced
      electrocatalytic activity towards the reduction of H(2)O(2) in the concentration
      range of 3.26*10(-6)M to 3.2*10(-3)M with a detection limit of 1.08*10(-6)M
      (S/N=3). The proposed electrode exhibited good stability and reproducibility, and
      it has the potential application as a sensor for other biologically significant
      compounds.

PMID- 22609589
TI  - Curcumin loaded mixed micelles composed of Pluronic P123 and F68: preparation,
      optimization and in vitro characterization.
AB  - In this study, curcumin (Cur) loaded mixed micelles (Cur-PF), composed of
      Pluronic P123 (P123) and Pluronic F68 (F68), was prepared using the thin-film
      hydration method and evaluated in vitro. The preparation process was optimized
      with a central composite design (CCD). The average size of the mixed micelles was
      68.2 nm, and the encapsulating efficiency for Cur was 86.93%, and 6.996% for drug
      loading. Compared with the Cur propylene glycol solution, the in vitro release of
      Cur from Cur-PF presented the sustained-release property. The in vitro
      cytotoxicity assay showed that the IC(50) values on MCF-7 cells for Cur-PF and
      free Cur in DMSO solution were 5.04 MUg/mL and 8.35 MUg/mL, while 2.52 MUg/mL and
      8.27 MUg/mL on MCF-7/ADR cells. It could be concluded from the results that
      P123/F68 mixed micelles might serve as a potential nanocarrier to improve the
      solubility and biological activity of Cur.

PMID- 22609590
TI  - Formulation and evaluation of Nimodipine-loaded solid lipid nanoparticles
      delivered via lymphatic transport system.
AB  - In an attempt to increase oral bioavailability and to target intestinal lymphatic
      transport system, Nimodipine loaded solid lipid nanoparticles (NMD-SLNs) were
      prepared. Nimodipine (NMD) is highly lipophilic antihypertensive drug having
      (logP 3.41) and 13% oral bioavailability. NMD-SLNs were prepared with palmitic
      acid (PA), poloxamer 188 and soya lecithin as a lipid, surfactant and co
      surfactant respectively using high pressure homogeniser. A (2(3)) factorial
      design was employed; three factors such as lipid, surfactant and co-surfactant
      concentration were used. Parameters investigated includes particle size,
      polydispersity index (PDI), zeta potential, drug entrapment efficiency (EE %),
      drug loading efficiency (LE %), in vitro drug release of the SLNs. Optimised SLNs
      (F8) had particle size of 116+/-21 nm, zeta potential of -10+/-(-4.8) mV, EE of
      93.66+/-9.72% and cumulative drug release of 87.52+/-2.54% in 10 h. The
      pharmacokinetic study of optimised SLNs conducted in male Albino Wistar rats
      showed 2.08-fold increase in relative bioavailability than that of NMD solution,
      when administered orally. Differential scanning calorimetry study revealed
      absence of any chemical interaction between NMD and PA while SEM study confirmed
      the non spherical shape of optimised SLNs. Accelerated stability studies showed
      that there was no significant change in the mean particle size and PDI after
      storage at 25+/-2 degrees C/60+/-5% RH for the period of three months. Due to
      enhanced bioavailability, these NMD-SLNs are considered to be promising vehicles
      for oral delivery.

PMID- 22609591
TI  - PLGA-based nanoparticles: effect of chitosan in the aggregate stabilization. A
      dielectric relaxation spectroscopy study.
AB  - Chitosan-modified polylactic-co-glycolic acid (PLGA) nanoparticles with average
      diameter of 200 nm in PBS buffer solution have been investigated by means of
      dielectric relaxation spectroscopy measurements in the frequency range (1 MHz-2
      GHz) where interfacial polarizations occur. PLGA-based nanoparticles offer
      remarkable advantages in different biotechnological fields, such as their
      biocompatibility, easiness of administration and rather complete biodegradation.
      However, despite the use of these drug delivery systems is increasing, little is
      known about the basic process involved in the formation of complexes and in the
      subsequent release kinetics. In the present work, we have characterized the
      colloidal behavior of PLGA-based nanoparticles in the presence of oppositely
      charged chitosan polyelectrolyte by means of dynamic light scattering,
      electrophoretic mobility and radiowave dielectric relaxation measurements. In
      particular, we have emphasized how the presence of a coating layer at the
      nanoparticle surface could exert a marked slowing-down in the drug release. The
      consequence of this finding is briefly discussed at the light of some biological
      implications.

PMID- 22609592
TI  - Plasma polymer films as an alternative to (PSS-PAH)n or (PSS-PDADMAC)n films to
      retain active enzymes in exponentially growing polyelectrolyte multilayers.
AB  - Compact and linearly growing polyelectrolyte multilayer films have been used to
      suppress desorption of drugs, nanoparticles or proteins from underlying
      polyelectrolyte multilayer films as well as to significantly change their
      mechanical properties. The polyelectrolyte based capping layers are however
      cumbersome to deposit and alternative barrier layers offering enzymatic retention
      in the films as well as permeability to small molecules, for example the
      substrates of the embedded enzymes, are highly desired. In this article we show
      that barrier layers made through atmospheric pressure dielectric barrier
      discharge polymerization of ethylene glycol dimethacrylate offer the opportunity
      to simultaneously suppress enzyme desorption from the underlying polyelectrolyte
      multilayer film and to ensure accessibility of the enzymatic substrate. This
      holds true when the barrier film totally covers the underlying film and as long
      is not too thick. When the plasma deposited barrier becomes 300 nm thick, the
      hydrolysis curve of the enzyme presents a lag phase typical of a diffusion
      limited process.

PMID- 22609593
TI  - In situ formation of chitosan-gold hybrid hydrogel and its application for drug
      delivery.
AB  - A novel chitosan-gold (CS-Au) hybrid hydrogel was developed from chitosan and
      chloroauric acid in aqueous solution. Its physiochemical characteristics,
      including UV absorption, structure, morphology, swelling properties were studied.
      The CS-Au hybrid hydrogel exhibited an excellent water-absorbing property and
      could be applied as a drug delivery system for anticancer drug: doxorubicin (DOX)
      due to its high equilibrium water swelling content. The drug loading and release
      experiments elicited an efficient drug loading content and sustained drug release
      pattern. Moreover, DOX released from hydrogel which itself had no cytotoxicity
      was biological active similar as the free DOX, but lower cytotoxicity due to its
      controllable release. All proved it an ideal local drug delivery system
      indicating a promising potential future in medical or pharmaceutical area.

PMID- 22609594
TI  - Adhesion of nano-sized particles to the surface of bacteria: mechanistic study
      with the extended DLVO theory.
AB  - Due to the increasing production and application of nanoparticles, their release
      into the environment would be inevitable, which requires a better understanding
      of their fate in the environment. When considering their toxic behavior or
      biodegradation as their fate, their adhesion to the cell surface must be the
      first step to be thoroughly studied. In this study, nano-sized polymeric
      particles of urethane acrylate with various hydrophobicity and ionic properties
      were synthesized as model nanoparticles, and their adhesion to Pseudomonas putida
      strains was monitored. The higher hydrophobicity and positive charge density on
      the particle surface exhibited the larger adhesion to the bacteria, whereas
      negative charge density on the particle hindered their adhesion to the bacteria,
      albeit high hydrophobicity of particle. These observations were successfully
      explained with the extended Derjaguin-Landau-Verwey-Overbeek (DLVO) theory.

PMID- 22609595
TI  - A novel and simple approach for synthesis of palladium nanoparticles on carbon
      nanotubes for sensitive hydrogen peroxide detection.
AB  - In this paper, we have demonstrated a new carbon nanotubes (CNTs) composite
      sensor with Pd nanoparticles prepared by seed-mediated growth method, using 3.5
      nm gold nanoparticles as seeds and CNTs as growth scaffold. Their morphological
      characterization was carried out by scanning electron microscopy (SEM) and
      transmission electron microscope (TEM). Cyclic voltammetry and chronoamperometry
      were employed to characterize the performance of the modified electrode
      (PdNPs/AuNPs/CNTs/chitosan (chit) electrode). The results showed that the
      modified electrode had obvious electrochemical activity for electrocatalytic
      reduction of hydrogen peroxide (H(2)O(2)) at -0.2V. Low detection limit of 0.1
      MUM with wide linear range from 0.1 MUM to 6 mM could be obtained. The results of
      the experiment also showed that the sensor exhibits good reproducibility and long
      term stability, as well as high selectivity with no interference from other
      oxidable species.

PMID- 22609596
TI  - Highly sensitive electrochemical impedance sensing of PEP gene based on
      integrated Au-Pt alloy nanoparticles and polytyramine.
AB  - Fabrication of an electrochemical impedimetric DNA biosensor based on the
      integration of Au-Pt alloy nanoparticles (Au-Pt(NPs)) and electropolymerized
      polytyramine (Pty) film for the detection of phosphoenolpyruvate carboxylase
      (PEP) gene is described in this article, where Pty films acted as an ideal
      combination platform for Au-Pt(NPs) via electrostatic adsorption. The
      electrochemical properties of the Au-Pt(NPs)/Pty, the characteristics of the
      immobilization and hybridization of DNA were investigated by cyclic voltammetry,
      differential pulse voltammetry and electrochemical impedance spectroscopy (EIS),
      respectively. Primary study indicated that Au-Pt(NPs)/Pty had a synergistic
      effect on the electrochemical signal of [Fe(CN)(6)](3-/4-), which served as the
      classic redox probe in the most electrochemical impedimetric sensors. DNA
      sequence-specific of PEP transgene existed in some transgenic crops was detected
      by this EIS protocol. The dynamic detection range of this DNA electrochemical
      biosensor to the DNA target sequence was from 1.0*10(-12)M to 1.0*10(-7)M. The
      detection limit was measured to be 3.6*10(-13)M. The DNA biosensor also had good
      selectivity, stability and reproducibility.

PMID- 22609597
TI  - Lipid exchange between membranes: effects of membrane surface charge,
      composition, and curvature.
AB  - Intermembrane lipid exchange is critical to membrane functions and pharmaceutical
      applications. The exchange process is not fully understood and it is explored by
      quartz crystal microbalance with dissipation monitor method in this research. It
      is found that intermembrane lipid exchange is accelerated with the decrease of
      vesicle size and the increase of charge and liquid crystalline lipid composition
      ratio. Vesicle adsorption rate, membrane lateral pressure gradient, and lipid
      lateral diffusion coefficient are inferred to be critical in deciding the lipid
      exchange kinetics between membranes. Besides that, the membrane contact situation
      during lipid exchange is also studied. The maximum total membrane contact area is
      found to increase with the decrease of vesicle size, charged and liquid
      crystalline lipid composition ratio. A competition mechanism between the vesicle
      adsorption rate and the intermembrane lipid exchange rate was proposed to control
      the maximum total membrane contact area.

PMID- 22609598
TI  - Towards the understanding of the behavior of single-chained ether phospholipids
      in model biomembranes: interactions with phosphatidylethanolamines in Langmuir
      monolayers.
AB  - Three single-chained ether lipids of comparable chemical structure but different
      biological activities (namely natural platelet activating factor - PAF, its
      deacetylated precursor - lyso-PAF and synthetic compound - edelfosine - ED) have
      been investigated in mixed Langmuir monolayers with phosphatidylethanolamines,
      PEs (DSPE, SOPE and DOPE), serving as model of inner shell of cellular membrane.
      The aim of undertaken studies was to verify the correlation between minor
      differences in chemical structures of the investigated ether lipids and their
      behavior in membrane-mimicking environment. To reach this goal the interactions
      between particular ether lipids and PEs have been analyzed with DeltaG(Exc)
      values derived from the surface pressure-area isotherms. To get insight into
      miscibility between film components, Brewster angle microscopy, enabling direct
      visualization of monolayers structure, has been applied. The obtained results
      prove significant differences in both mixing properties and the interactions in
      the investigated systems. On one hand, they are related to the structure of polar
      head-groups of the studied ether lipids, which determine their capability of
      hydrogen bond(s) formation with head-groups of PEs. Edelfosine, lacking this
      property, interacts with PEs the most unfavorably among all the investigated
      compounds. Another important parameter in this context is the structure of PEs
      monolayers - the most closely packed DSPE film was found to be most unfavorable
      for incorporation of ether lipid molecules. Our results prove that the analysis
      of the interaction between ether lipids and components of biomembrane in Langmuir
      monolayers is a potent method to explain differences in biological activity of
      the investigated ether lipids.

PMID- 22609599
TI  - Plasma treatment allows water suspending of the natural hydrophobic powder
      (lycopodium).
AB  - Lycopodium particles which are spores of the plant Lycopodium clavatum were
      exposed to cold oxygen and nitrogen plasma irradiation. Wetting properties of the
      particles changed dramatically from hydrophobic to hydrophilic. Plasma treatment
      allowed obtaining stable water suspensions of lycopodium. Plasma treatment did
      not affect the morphology of lycopodium particles. The reported results open the
      way for surfactants-free manufacturing suspensions of hydrophobic particles.

PMID- 22609600
TI  - Synthesis and cellular uptake of scatteredly cyclic RGDfK-conjugated
      superparamagnetic iron oxide nanoparticles.
AB  - We prepared scatteredly cyclic RGDfK-conjugated water-dispersible
      superparamagnetic iron oxide nanoparticles (cRGDfK-WSPIONs) and investigated
      their cellular uptake to MS-1 cells (mouse endothelial cell lines, express
      integrin alpha(v)beta(3)) and MCF-7 cells (human breast cancer cells, express low
      level of integrin alpha(v)beta(3)) using in vitro MRI. The cRGDfK-WSPIONs were
      prepared from oleate-protected SPIONs (SPION-OA) as follows. Some oleates (OAs)
      on the SPION-OA were substituted by mercaptohexadecanoic acids (MHA) and cRGDfKs
      were conjugated to MHAs. Finally, the remaining OAs were substituted by
      mercaptopropionic acids without detaching preexisting cRGDfK-conjugated MHA
      ligands from the SPION surface. The cRGDfK-WSPIONs showed drastically higher
      cellular uptake than its corresponding control WSPIONs to MS-1 cells and also,
      showed higher selectivity to MS-1 cells than to MCF-7 cells, both implicating
      integrin alpha(v)beta(3)-mediated cellular uptake of scatteredly cRGDfK
      conjugated WSPIONs.

PMID- 22609601
TI  - Synthesis, characterization and drug release behavior of poly(1-vinyl 1,2,4
      triazole) hydrogels prepared by gamma irradiation.
AB  - Crosslinked poly(1-vinyl 1,2,4-triazole) (PVTAz) hydrogels in the form of rod and
      hollow cylinder (thin and thick wall) have been prepared by (60)Co gamma
      radiation initiated simultaneous polymerization and crosslinking of 1-vinyl 1,2,4
      triazole in the presence of water. In binary aqueous systems, the degree of
      gelation decreased with the increasing water content. The swelling results
      obtained by using different form of hydrogels showed that the thin wall hollow
      cylinder hydrogels perform better than other hydrogels. Structural, morphological
      and thermal characterizations of the hydrogels were carried out with several
      techniques, including Fourier transform infrared spectroscopy, scanning electron
      microscopy, swelling measurements, thermogravimetry, and differential scanning
      calorimetry. The effects of time, pH, temperature, ionic strength, and salt and
      solvent type on the swelling behavior of thin wall hollow cylinder hydrogels were
      also investigated. Swelling equilibrium was attained in 2 days. Thin wall hollow
      cylinder PVTAz hydrogels originally swelled to 3000% (by volume), and depending
      on the pH value, no sharp change was observed on the swelling curve. Swelling
      values of hydrogels showed that the swelling ratio increase with the increasing
      temperature in the range of 4-20 degrees C. The swelling ratios of the gels
      decreased with increasing ionic strength. Hydrogels have shown the maximum
      contraction in the presence of LiCl. 5-Fluorouracil (5-FU) was loaded on PVTAz
      hydrogels by using incorporation and adsorption methods. Both methods show the
      similar release profiles. Time-dependent release of 5-FU was achieved within 48 h
      by the success of 65%. All these results showed that PVTAz hydrogels are suitable
      for the release of 5-FU in the applications of long-term cancer treatment.

PMID- 22609602
TI  - Poly(L-aspartic acid) derivative soluble in a volatile organic solvent for
      biomedical application.
AB  - In order to develop a novel functional poly(L-amino acid) that can dissolve in
      volatile organic solvents, we prepared poly[L-aspartic acid-g-(3
      diethylaminopropyl)]-b-poly(ethylene glycol) [poly(L-Asp-g-DEAP)-b-PEG] via the
      conjugation of 3-diethylaminopropyl (DEAP) to carboxylate groups of poly(L-Asp)
      (M(n) 4 K)-b-PEG (M(n) 2 K). This poly(L-aspartic acid) derivative evidenced a
      relatively high solubility in volatile organic solvents such as dichloromethane,
      chloroform, and acetone. We fabricated a model nanostructure (i.e., polymeric
      micelle) using poly(L-Asp-g-DEAP)-b-PEG by the film rehydration method, which
      involves the simple removal of the volatile organic solvent (dichloromethane)
      used to dissolve polymer, reducing concerns about organic solvents remaining in a
      nano-sized particle. Interestingly, this micelle showed the pH-stimulated release
      of encapsulated model drug [i.e., doxorubicin (DOX)] due to the protonation of
      DEAP according to the pH of the solution. We expect that this poly(L-aspartic
      acid) derivative promises to provide pharmaceutical potential for constituting a
      new stimuli-sensitive drug carrier for various drug molecules.

PMID- 22609603
TI  - Alkyl triazole glycosides (ATGs)--a new class of bio-related surfactants.
AB  - A series of glucose based surfactants varying in chain length and anomeric
      configuration were synthesized and investigated on their surfactant properties.
      The synthesis applied glycosylation of propargyl alcohol followed by
      cycloaddition with alkyl azides in CLICK chemistry fashion. This approach enables
      a homogeneous coupling of hydrophilic unprotected sugars and hydrophobic paraffin
      components in low molecular weight alcohols without solvent side reactions, as
      commonly found for APGs. The combination of alcohols as inert medium with
      practically quantitative coupling of the surfactant domains avoids particularly
      hydrophobic contaminations of the surfactant, thus providing access to pure
      surfactants. ATGs with chain lengths up to 12 carbons exhibit Krafft points below
      room temperature and no cloud points were detected. The values for the CMC of
      ATGs with 12 carbon alkyl chains and above were in good agreement with those of
      corresponding alkyl glucosides. However, lower homologues exhibited significantly
      smaller CMCs, and the trend of the CMC upon the chain length did not match common
      surfactant behavior. This deviation may be related to the triazole that links the
      two surfactant domains.

PMID- 22609604
TI  - Smart copper oxide nanocrystals: synthesis, characterization, electrochemical and
      potent antibacterial activity.
AB  - We report herein the synthesis and characterization of novel CuO nanocrystals and
      their electrochemical and potent antibacterial activity. The utilized CuO
      nanocrystals were prepared by wet chemical method using copper acetate and
      hexamethylenetetramine (HMTA) as precursors. The physicochemical properties of
      the synthesized CuO nanocrystals having size ~6 nm were determined by X-ray
      diffractometer (XRD), energy dispersive X-ray analysis (EDX), transmission
      electron microscopy (TEM) and ultra violet-visible (UV-Vis) spectroscopy. The
      antibacterial study was carried out by minimum inhibitory concentration (MIC)
      using E. coli as model organism. The MIC of the CuO nanocrystals was found to be
      2.5 MUg/ml and the TEM analysis reveals that CuO nanocrystals caused disturbance
      to the cell wall which led to the irreversible damage to the cell envelope
      eventually leading to cell death. Furthermore, mechanism of bactericidal action
      of novel CuO nanocrystals is discussed in the light of our findings.
      Additionally, the synthesized CuO nanocrystals were applied as electrode material
      for supercapacitor. The specific capacitance of CuO nanocrystals measured at a
      potential scan rate of 5 mV/s was as high as 164.9 F g(-1).

PMID- 22609605
TI  - Phase effect of mixed-phospholipid layer on phospholipase D reaction-induced
      vesicle rupture.
AB  - Spherical phospholipid-bilayers, vesicles, were prepared through layer by layer
      using double emulsion technique, which allows the outer layer of the vesicles to
      be formed with two phospholipids that have different headgroups -
      phosphatidylcholine (PC) and phosphoethanolamine (PE). At the outer layer of the
      vesicles, the phospholipase D (PLD) reacted on the layer to convert
      phosphatidylcholine (PC) to phosphatidic acid (PA). The reaction induced the
      curvature change of the vesicles, which eventually led to the rupture of the
      vesicles. Response time from the PLD injection to the rupture was measured at
      each phase of the layer made with the different-composition lipids, using the
      fluorescence intensity change of pH-sensitive dye encapsulated in the vesicles.
      It was found that the retardation of the response time started at different
      composition up on the phase. At the liquid phase, the composition was 30% PC,
      while the composition at the solid phase was 20% PC. The difference was
      interpreted with the surface density of PC at the layer, which was varied with
      the phase. Furthermore, the difference was also caused by the size of PLD active
      site, not PLD.

PMID- 22609606
TI  - Regulation of the behaviors of mesenchymal stem cells by surface nanostructured
      titanium.
AB  - The study describes the influence of surface nanostructured titanium substrates
      on the growth behaviors of mesenchymal stem cells. Surface nanostructures of
      titanium were produced with surface mechanical attrition treatment (SMAT)
      technique. The morphologies of native titanium and surface nanostructured
      titanium substrates were characterized by field emission scanning electron
      microscopy (FE-SEM), atomic force microscopy (AFM), transmission electron
      microscopy (TEM), X-ray diffraction (XRD) and contact-angle measurements,
      respectively. A thin nanostructured layer was formed onto the surfaces of
      titanium substrates after SMAT treatment. The effects of the surface
      nanostructured titanium substrates on the adhesion, spreading, proliferation and
      differentiation of mesenchymal stem cells (MSCs) was examined at cellular and
      molecular levels in vitro. The results suggest that the surface nanostructured
      substrates were beneficial for the growth of MSCs, including adhesion, filament
      orientation, proliferation and gene expression. This approach for the fabrication
      of surface nanostructured titanium may be exploited in the development of high
      performance titanium-based implants.

PMID- 22609607
TI  - Cytotoxicity evaluation of magnetite (Fe3O4) nanoparticles in mouse embryonic
      stem cells.
AB  - Magnetite nanoparticles are expected to be applied in the medical field because
      of their biocompatibility and high saturated magnetization. In this paper,
      magnetite nanoparticles with a diameter of approximately 40 nm were evaluated for
      their safety by using mouse embryonic stem (mES) cells. First, various doses of
      magnetite nanoparticles were added to mES cells to find an optimal dose and to
      evaluate viability and keeping undifferentiated states of mES. The uptake of
      nanoparticles by mES cells was confirmed by using cytospin and transmission
      electron microscopy. Next, mES cells containing magnetite nanoparticles were
      collected by a magnet column 24h after the addition of magnetite nanoparticles,
      and the change in the ratio of those mES cells to the total mES cells was assayed
      by FACS 0, 4, 8, 12, 16, 24, 48 and 72 h after incubation. The result showed that
      the ratio decreased with time, indicating that the mES cells excreted the
      nanoparticles, for there was no change in the total number of cells. Based on
      these results, it was concluded that magnetite nanoparticles were safe to mES
      cells.

PMID- 22609608
TI  - Synthesis of copolymers using dendronized polyethylene glycol and assay of their
      blood compatibility and antibacterial adhesion activity.
AB  - Thrombus formation and microbial invasion are two major complications that impede
      the widespread application of blood-contacting devices. The development of new
      materials that have blood compatibility and antibacterial adhesion activity has
      gained increased attention. In this study, a new class of polymers composed of
      hydrophilic dendronized polyethylene glycol (PEG) methacrylate and hydrophobic
      octyne monomethyl ether-glycidyl methacrylate was synthesized via click chemistry
      and free radical polymerization. Different polymers were synthesized by changing
      the ratio of the two monomers. The structures of the synthesized polymers were
      characterized by (1)H nuclear magnetic resonance and Fourier-transform infrared
      spectroscopy. Their physical properties such as molecular weight, polydispersity,
      and glass transition temperature were determined using gel permeation
      chromatography and differential scanning calorimetry. The synthesized polymers
      were coated on glass slides to prepare a series of polymeric surfaces. Contact
      angle measurements and attenuated total reflection Fourier-transform infrared
      spectroscopy analysis showed that the polymeric surfaces had long-lasting
      stability. The introduction of the monomer dendronized PEG methacrylate to the
      polymers greatly improved the hydrophilicity of the polymeric surfaces. The blood
      compatibility of the synthesized polymers was evaluated by protein (bovine serum
      albumin and fibrinogen) adsorption and platelet adhesion assays. Their
      antibacterial adhesion ability was investigated using the Gram-negative
      Pseudomonas aeruginosa and the Gram-positive Staphylococcus aureus. The results
      demonstrated that the amount of adsorbed protein, platelets, and bacteria on the
      polymeric surfaces decreased with increased content of the hydrophilic monomer
      dendronized PEG methacrylate in the polymers. However, no obvious difference was
      observed when such content exceeded 50 mol%. The results suggested that the new
      kind of polymer could be developed as a promising blood-contact coating material
      that may have extensive medical applications.

PMID- 22609609
TI  - Synthesis of nanosized porous hydroxyapatite granules in hydrogel by
      electrophoresis.
AB  - Nanosized porous hydroxyapatite (HA) granules are expected to be useful as DNA
      and drug carriers for cells. We attempted to synthesize nanosized HA granules in
      an agarose gel by electrophoresis of calcium and phosphate ions. Wells were
      prepared on an agarose gel, and a CaCl(2) solution was placed in the wells on the
      positive side and a Na(2)HPO(4) solution was placed in the wells on the negative
      side. After a potential was applied, white precipitates appeared in the gel. The
      precipitates were calcium-deficient HA granules of approximately 300-600 nm in
      diameter. These granules were composed of fiber-like particles and had a porous
      structure. The diameters of the granules were decreased by an increase in the gel
      concentration. Hence, we successfully synthesized nanosized porous HA granules to
      be used as DNA and drug carriers.

PMID- 22609611
TI  - Efavirenz is not a known teratogen.

PMID- 22609610
TI  - Acidogenic potential of soy and bovine milk beverages.
AB  - Soy beverages are water extracts of whole soybeans and are often promoted as a
      healthy alternative to bovine milk. Little analysis has been carried out to
      determine the effects of soy beverages on oral health, especially their potential
      acidogenicity. OBJECTIVES: The aim of this study was to determine the potential
      acidogenicity of a range of soy and bovine milk beverages. METHODS: In vitro acid
      production by Streptococcus mutans was measured in soy and milk beverages at a
      constant pH of 6.5 or 5.5, as was the fall in pH over a 10 min period. The acid
      buffering capacity and calcium and phosphate concentrations (total and soluble)
      of the beverages were also determined. RESULTS: The rate of acid production by S.
      mutans in the milk beverages was five to six times lower at pH 6.5 than in the
      soy beverages and three to five times lower at pH 5.5. Whilst the pH fall in the
      presence of S. mutans over 10 min was negligible in the milk beverages there was
      a significant decrease in pH in the soy beverages. This was also reflected in the
      lower buffering capacity of the soy beverages. The levels of soluble calcium in
      the soy beverages were lower than those in the milk beverages although total
      calcium contents were similar. CONCLUSIONS: Soy beverages have a higher potential
      acidogenicity than bovine milk beverages. CLINICAL SIGNIFICANCE STATEMENT:
      Patients consider soy beverages to be a healthy, low cariogenic alternative to
      other beverages, including bovine milk. This study shows that soy beverages have
      a higher potential acidogenicity than bovine milk and therefore may have a
      greater potential cariogenicity.

PMID- 22609615
TI  - Regulation of the ATPase activity of ABCE1 from Pyrococcus abyssi by Fe-S cluster
      status and Mg2+: implication for ribosomal function.
AB  - Ribosomal function is dependent on multiple proteins. The ABCE1 ATPase, a unique
      ABC superfamily member that bears two Fe4S4 clusters, is crucial for ribosomal
      biogenesis and recycling. Here, the ATPase activity of the Pyrococcus abyssi
      ABCE1 (PabABCE1) was studied using both apo- (without reconstituted Fe-S
      clusters) and holo- (with full complement of Fe-S clusters reconstituted post
      purification) forms, and is shown to be jointly regulated by the status of Fe-S
      clusters and Mg2+. Typically ATPases require Mg2+, as is true for PabABCE1, but
      Mg2+ also acts as a negative allosteric effector that modulates ATP affinity of
      PabABCE1. Physiological [Mg2+] inhibits the PabABCE1 ATPase (K(i) of ~1 MUM) for
      both apo- and holo-PabABCE1. Comparative kinetic analysis of Mg2+ inhibition
      shows differences in degree of allosteric regulation between the apo- and holo
      PabABCE1 where the apparent ATP K(m) of apo-PabABCE1 increases >30-fold from ~30
      MUM to over 1 mM with M2+. This effect would significantly convert the ATPase
      activity of PabABCE1 from being independent of cellular energy charge (phi) to
      being dependent on phi with cellular [Mg2+]. These findings uncover intricate
      overlapping effects by both [Mg2+] and the status of Fe-S clusters that regulate
      ABCE1's ATPase activity with implications to ribosomal function.

PMID- 22609616
TI  - Characterization of the Kv1.1 I262T and S342I mutations associated with episodic
      ataxia 1 with distinct phenotypes.
AB  - Episodic ataxia type 1 (EA-1) is an autosomal dominant neurological disorder
      caused by mutations in the potassium channel Kv1.1. Two EA-1 mutations, I262T and
      S342I, have been identified with unique clinical phenotypes, but their functional
      and biochemical properties have not been fully investigated. Here we
      characterized these two mutations in transfected mammalian cells both
      electrophysiologically and biochemically. We found that the I262T mutation
      resulted in a ~7-fold reduction in the K+ current amplitude compared with wild
      type channels, whereas the S342I mutation produced an apparent nonfunctional
      channel when expressed alone. Co-expression of wild type and mutant channels
      showed that both I262T and S342I exerted dominant-negative effects on wild type
      function. The protein expression analysis showed that I262T resulted in ~2-fold
      decrease in surface protein levels of Kv1.1, which partially contributed to the
      decreased surface conductance density, whereas the S342I mutation showed no
      effects on surface protein expression. Conservative amino acid substitution
      experiments suggest that the wild type amino acids at these two positions are
      required for normal channel function. Our results broaden the knowledge of EA-1
      mutations and the underlying mechanisms of the associated disorder.

PMID- 22609617
TI  - Ab initio calculation of strain effect on the magnetic properties of the
      thiogermanate [(CH3)4N]2FeGe4S10.
AB  - The magnetic properties of the thiogermanate TMA(2)FeGe(4)S(10)
      (TMA=[(CH(3))(4)N](+)), and the influence of large strain are investigated by ab
      initio density functional theory calculations. An analysis of the electronic
      structure is provided considering antiferromagnetic (AFM), ferromagnetic (FM) and
      nonmagnetic configurations for the thiogermanate at the equilibrium states. A
      small difference in total energy between the FM and AFM states suggests that the
      thiogermanate TMA(2)FeGe(4)S(10) may possess a low Curie temperature. Changes in
      electronic structure and magnetic moment of the thiogermanate under strain are
      closely related to the distortion of FeS(4) tetrahedral units. With the help of a
      simplified molecule model, we show that, while the origin of the drastic change
      in magnetism under high isotropic compressions mainly originates from the
      decrease in the Fe-S interatomic bond length, the changes in the electronic
      structure between - 10% and + 15% isotropic strains are mainly due to the
      variations of the interatomic bond angles. Little effect of shear strain on the
      magnetic properties is found since the FeS(4) tetrahedral units rotate under
      shear, hence keeping their shape.

PMID- 22609618
TI  - Field match verification during combination proton, photon, and electron therapy
      for oligometastatic inflammatory breast cancer.
AB  - Postmastectomy radiation therapy (PMRT) has been shown in randomized trials to
      improve overall survival for patients with locally advanced breast cancer. The
      standard PMRT clinical target volume (CTV) encompasses the chest wall and
      undissected regional lymphatics. Conformal isodose distributions covering the
      standard CTV with acceptable dose limits to normal tissue can typically be
      achieved with a combination of photon and electron fields. Field borders are
      marked on the patient's skin using a light field projection of each beam and are
      subsequently used to verify daily field matching clinically. Initial imaging of a
      patient with oligometastatic inflammatory breast cancer demonstrated direct
      extension of disease from the involved internal mammary lymph node chain into the
      anterior mediastinum as the only site of metastatic disease. The patient achieved
      a pathologic complete response to neoadjuvant chemotherapy and underwent
      mastectomy. The initial sites of gross disease, including the anterior
      mediastinal node was included in the CTV for PMRT, and treatment planning
      demonstrated a clear advantage to the inclusion of proton fields in this case.
      The absence of a light source on the proton delivery system that accurately
      projects proton field edges onto the patient's skin posed a significant challenge
      for daily verification of proton-to-photon and -electron field matching. Proton
      field-specific radiographic imaging devices were designed and used such that
      proton field edges could be delineated on the patient's skin and used for daily
      matching with photon and electron fields. Manufacture of the imaging devices was
      quick and inexpensive. Weekly verification of proton field alignment with the
      proton field delineation on the skin demonstrated agreement within 3-mm
      tolerance. The patient remains with no evidence of disease 18 months after
      completing radiation. Other patients with similar indications may benefit from
      multimodality radiation therapy.

PMID- 22609619
TI  - Acute dopamine boost has a negative effect on plasticity of the primary motor
      cortex in advanced Parkinson's disease.
AB  - Plasticity of primary motor cortex is severely impaired in Parkinson's disease
      and chronic dopaminergic treatment is reported not to rescue it. The effect of an
      acute dose of levodopa on cortical plasticity reported so far is variable. In
      this study, it was hypothesized that cortical plasticity would be restored in
      Parkinson's disease as a long duration response to treatment in stable responders
      while those with motor complications would have a reduction or loss of plasticity
      similar to the decay of long duration response of motor signs. Patients were
      carefully stratified based on their motor response to levodopa into stable
      responders (n=17), fluctuating non-dyskinetics (n=18) and fluctuating dyskinetics
      (n=20). Theta burst stimulation was applied to the motor cortex to induce long
      term potentiation and long-term depression-like plasticity in both OFF and ON
      conditions. In OFF, stable responders could express both types of plasticity,
      fluctuating non-dyskinetics had long-term potentiation, but no long-term
      depression and both types of plasticity were lost in fluctuating dyskinetics.
      This suggests the presence of a long duration response in early stages of
      levodopa treatment and a gradual loss of chronic treatment benefit on plasticity,
      particularly for long-term depression, when motor complications develop. An acute
      dose of levodopa led to a worsening of long-term potentiation in fluctuating non
      dyskinetic patients, and it did not have any effect on the plasticity that was
      absent in OFF in the fluctuating dyskinetic patients. Acute dosing led to a
      worsening of long-term depression in all the groups. In the fluctuating
      dyskinetic patients, there was a paradoxical potentiation instead of depression.
      Our results suggest that an acute non-physiological dopamine boost has a negative
      effect on cortical plasticity as disease advances. We propose that the loss of
      long duration response and the negative effect of acute doses on cortical
      plasticity with progression of disease may contribute to the pathophysiology of
      motor complications. Repeated non-physiological surges in synaptic dopamine
      during acute levodopa dosing could potentially lead to persistent dysfunction of
      key enzymes of the intracellular signalling cascade that are involved in the
      induction and maintenance of both forms of plasticity.

PMID- 22609620
TI  - Comparison of ERCC1/XPF genetic variation, mRNA and protein levels in women with
      advanced stage ovarian cancer treated with intraperitoneal platinum.
AB  - OBJECTIVE: Approximately 20% of patients receiving platinum-based chemotherapy
      for epithelial ovarian cancer (EOC) are refractory or develop early recurrence.
      Identifying these patients early could reduce treatment-associated morbidity and
      allow quicker transfer to more effective therapies. Much attention has focused on
      ERCC1 as a potential predictor of response to therapy because of its essential
      role in the repair of platinum-induced DNA damage. The purpose of this study was
      to accurately measure protein levels of ERCC1 and its essential binding partner
      XPF from patients with EOC treated with platinum-based therapy and determine if
      protein levels correlate with mRNA levels, patient genotypes or clinical
      outcomes. METHODS: ERCC1 and XPF mRNA and protein levels were measured in frozen
      EOC specimens from 41 patients receiving intraperitoneal platinum-based
      chemotherapy using reverse transcription polymerase chain reaction and western
      blots. Genotypes of common nucleotide polymorphisms were also analyzed. Patient
      outcomes included progression free (PFS) and overall survival (OS). RESULTS:
      Expression of ERCC1 and XPF were tightly correlated with one another at both the
      mRNA and protein level. However, the mRNA and protein levels of ERCC1 were not
      positively correlated. Likewise, none of the SNPs analyzed correlated with ERCC1
      or XPF protein levels. There was an inverse correlation between mRNA levels and
      patient outcomes. CONCLUSION: Neither genotype nor mRNA levels are predictive of
      protein expression. Despite this, low ERCC1 mRNA significantly correlated with
      improved PFS and OS.

PMID- 22609621
TI  - Contribution of microRNA-203 to the isoflurane preconditioning-induced
      neuroprotection.
AB  - A prior exposure to isoflurane, a common volatile anesthetic, provides
      neuroprotection (isoflurane preconditioning). To determine the role of microRNAs
      in this protection, we performed microRNA array assay on cerebral cortex
      harvested from rats exposed to isoflurane or isoflurane-exposed rat B35 neuron
      like cells. We showed that isoflurane significantly increased microRNA-203
      expression in B35 neuron-like cells. The microRNA-203 expression in rat cerebral
      cortex also trended to increase after isoflurane exposure. Over-expression of
      microRNA-203 increased the tolerance of B35 cells to oxygen-glucose deprivation
      and the expression of phospho-Akt, a protein kinase that promotes cell survival.
      Isoflurane preconditioning also reduced the injury of these cells after oxygen
      glucose deprivation. These results suggest that isoflurane preconditioning
      induced neuroprotection may involve increased expression of microRNA-203. This
      finding provides the initial evidence that micoRNA-203 is a target for isoflurane
      in the brain.

PMID- 22609622
TI  - Glucocorticoid receptor antagonism blocks ethanol-induced place preference
      learning in mice and attenuates dopamine D2 receptor adaptation in the frontal
      cortex.
AB  - The glucocorticoid receptor (GR) plays an important role in alcohol (EtOH) self
      administration behaviour by its interaction with the dopaminergic (DA) system in
      the brain. Here we asked whether the GR is also involved in the establishment of
      EtOH-induced conditioned place preference (CPP) by an interaction with the DA
      systems in terminal projection areas. We found that the establishment of an EtOH
      (2 g/kg, i.p.)-induced CPP was paralleled by a decrease in frontal cortex DA D2
      receptor mRNA expression, but not in local D2 gene promoter methylation rate. No
      effect in other brain areas, nor on DA transporter or DA receptor regulating
      factor mRNA was found. The GR antagonist, RU486 (20 mg/kg, i.p.) blocked the
      establishment of EtOH CPP and prevented DA D2 receptor adaptations. These data
      may suggest a role of glucocorticoid receptor mediated D2 adaptations in the
      establishment of the reinforcing effects of EtOH.

PMID- 22609623
TI  - A call to "image gently".

PMID- 22609624
TI  - The imperative for synthesizing evidence for pediatric nursing research and
      practice.

PMID- 22609625
TI  - 2b-RAD: a simple and flexible method for genome-wide genotyping.
AB  - We describe 2b-RAD, a streamlined restriction site-associated DNA (RAD)
      genotyping method based on sequencing the uniform fragments produced by type IIB
      restriction endonucleases. Well-studied accessions of Arabidopsis thaliana were
      genotyped to validate the method's accuracy and to demonstrate fine-tuning of
      marker density as needed. The simplicity of the 2b-RAD protocol makes it
      particularly suitable for high-throughput genotyping as required for linkage
      mapping and profiling genetic variation in natural populations.

PMID- 22609627
TI  - Posttraumatic growth: a psychiatric oddity.

PMID- 22609628
TI  - Post-traumatic stress disorder, associated medical illnesses, and suicidal
      behavior: plenty of room for new research.

PMID- 22609626
TI  - Facile backbone structure determination of human membrane proteins by NMR
      spectroscopy.
AB  - Although nearly half of today's major pharmaceutical drugs target human integral
      membrane proteins (hIMPs), only 30 hIMP structures are currently available in the
      Protein Data Bank, largely owing to inefficiencies in protein production. Here we
      describe a strategy for the rapid structure determination of hIMPs, using
      solution NMR spectroscopy with systematically labeled proteins produced via cell
      free expression. We report new backbone structures of six hIMPs, solved in only
      18 months from 15 initial targets. Application of our protocols to an additional
      135 hIMPs with molecular weight <30 kDa yielded 38 hIMPs suitable for structural
      characterization by solution NMR spectroscopy without additional optimization.

PMID- 22609629
TI  - Somatosensory factors in taste perception: effects of active tasting and solution
      temperature.
AB  - Touch and temperature are recognized as important factors in food perception, but
      much remains to be learned about how they contribute to the perception of flavor.
      The present paper describes human psychophysical studies that investigated two
      recently discovered effects of temperature and mechanical stimulation on taste:
      (1) enhancement of the savory taste of MSG by active tongue and mouth movements,
      and (2) modulation of the rate of adaptation to sucrose sweetness by temperature.
      The first study provides evidence that for MSG but not other taste stimuli,
      movement of the tongue against the palate enhances taste intensity both by
      increasing spatial summation between opposing gustatory surfaces and by a
      hypothesized interaction with touch/kinesthesis. The second study shows that the
      rate of adaptation to sucrose sweetness (but not quinine bitterness) on the
      tongue tip is strongly influenced by temperature. It is hypothesized that warming
      slows adaptation to sucrose by increasing the sensitivity of an early stage of
      taste transduction. Together these results demonstrate that models of flavor
      perception must include somatosensory stimuli both as components of flavor
      perception and as modulators of taste.

PMID- 22609630
TI  - Antiproliferative effect of normal and 13-epi-D-homoestrone and their 3-methyl
      ethers on human reproductive cancer cell lines.
AB  - The possibility of the therapeutic use of estrogens emerged following the
      recognition that certain estradiol analogs, and particularly metabolites (e.g.
      the A-ring metabolite 2-hydroxyestrone, etc.) inhibit the differentiation of
      diverse tumor cell lines. Until recently, despite the investigation of numerous
      synthetic d-ring-substituted estrone derivatives, no analysis had been published
      on the effects of D-ring expansion of estrone on its tumor-suppressing activity.
      The aim of the present study was to characterize the antiproliferative effects of
      normal and 13-epi-D-homoestrone and their 3-methyl ethers (1-4) on human
      reproductive cancer cell lines. The antitumor activities of the two epimer pairs
      on HeLa, MCF-7 and Ishikawa cells were determined. Normal D-homoestrone exerted
      the greatest cytostatic effect on HeLa cells (IC(50)=5.5 MUM) and was subjected
      to further investigations to elucidate its mechanism of action on apoptosis
      induction. Morphological changes detected by Hoechst 33258-propidium iodide
      double staining, the cell cycle arrest at phase G2/M and the subsequent increase
      in the proportion of the subG1 fraction determined by flow cytometric analysis
      and the significant increase in the activity of caspase-3 confirmed the induction
      of apoptosis in HeLa cells treated with D-homoestrone. D-Homoestrone was also
      tested on a non-cancerous human lung fibroblast cell line (MRC-5) to determine
      its selective toxicity. The concentration in which it inhibited cell
      proliferation by 50% was at least six times higher for the fibroblast cells than
      for cervical cancer cells. No significant in vivo estrogenic activity was
      observed as concerns the uterus weight of gonadectomized rats after a 7-day
      treatment with normal D-homoestrone. These results led to the conclusion that
      normal D-homoestrone is a novel antitumor compound with a similar activity on
      HeLa cells as that of the reference agent cisplatin, but its selectivity toward
      non-cancerous cells is significantly higher than that of cisplatin. It may be
      considered to be a basic lead molecule for the preclinical development of
      potential anticancer agents.

PMID- 22609631
TI  - Expression, purification and characterization of recombinant human interleukin-2
      serum albumin (rhIL-2-HSA) fusion protein in Pichia pastoris.
AB  - Interleukin-2 (IL-2) plays important roles in variety of immune functions.
      Recombinant IL-2 has become an important therapeutic protein for therapy of
      melanoma and renal cell carcinoma. Previously, it was proved that the therapeutic
      efficacy of rIL-2 expressed in Saccharomyces cerevisiae was improved by
      prolonging its in vivo half-life through genetic fusion with albumin. In this
      study, a fusion protein composed of hIL-2 genetically fused to HSA was expressed
      as a secretory protein under AOX1 (alcohol oxidase 1) promoter in Pichia
      pastoris. An effective strategy was established to express rhIL-2-HSA fusion
      protein in 5L scale and the optimal purification procedure was investigated. The
      purity of rhIL-2-HSA in final product was about 95%. The purified rhIL-2-HSA
      fusion protein could be recognized by both anti-hIL-2 and anti-human serum
      albumin monoclonal antibody. Bioactivity analysis showed that the purified rhIL-2
      HSA fusion protein displayed high level activity on proliferation in IL-2
      dependent manner in CTLL2-cells. rhIL-2-HSA fusion protein also showed a extended
      half-life in plasma compared with IL-2 when tested in a BALB/c mouse model. This
      study provides an alternative strategy for large-scale production of bioactive
      rhIL-2-HSA fusion protein using P. pastoris as an expression host.

PMID- 22609633
TI  - Journey as destination: a recovery model for families affected by concurrent
      disorders.
AB  - We conducted a study offering peer support and education to members of families
      affected by concurrent disorders (CD). This article is an analysis of the
      qualitative data from a mixed methods study. Using constructivist grounded
      theory, we analyzed semistructured interviews with participants, with half
      attending a 12-week support group and reading weekly workbook assignments, and
      the others receiving the workbook only and being interviewed 3 months later. We
      developed a model that describes family journeys into, through, and beyond CD,
      involving three phases connected by two transitional constructs. Preoccupation
      with the unresolved CD of an ill family member characterized the journey into and
      through illness, the first two phases, whereas renewal characterized the passage
      from illness to journeying on toward recovery. Participants had strong comments
      about health care providers and the service system, and spoke of the need for
      self-care, empowerment, support, and inclusion.

PMID- 22609634
TI  - Immobility, battles, and the journey of feeling alive: women's metaphors of self
      transformation through depression and recovery.
AB  - Australian mental health services have responded to the problem of depression by
      adopting an early intervention and recovery orientation. Using qualitative
      research conducted in Australia with 80 women aged 20 to 75 years, we examine how
      participants invoked particular metaphors to construct meaning about the gendered
      experience of depression and recovery. We argue that women's stories of recovery
      provide a rich source of interpretive material to consider the everyday metaphors
      of recovery beyond clinical notions and linear models of personal change. We
      identified key metaphors women drew on to articulate the struggle of self
      transformation through depression and recovery: the immobilizing effect of
      depression, recovery as a battle to control depression, and recovery as a journey
      of self-knowledge. Our findings might be useful for mental health professionals
      in a range of clinical contexts to reflect on the power of language for shaping
      how women interpret their experiences of recovery from depression.

PMID- 22609635
TI  - Development and initial evaluation of the spinal cord injury-functional index.
AB  - OBJECTIVES: To describe the calibration of the Spinal Cord Injury-Functional
      Index (SCI-FI) and report on the initial psychometric evaluation of the SCI-FI
      scales in each content domain. DESIGN: Cross-sectional survey followed by
      calibration data simulations. SETTING: Inpatient and community settings.
      PARTICIPANTS: A sample of participants (N=855) with traumatic spinal cord injury
      (SCI) recruited from 6 SCI Model Systems and stratified by diagnosis, severity,
      and time since injury. INTERVENTIONS: None. MAIN OUTCOME MEASURE: SCI-FI
      instrument. RESULTS: Item response theory analyses confirmed the
      unidimensionality of 5 SCI-FI scales: basic mobility (54 items), fine motor
      function (36 items), self-care (90 items), ambulation (39 items), and wheelchair
      mobility (56 items). All SCI-FI scales revealed strong psychometric properties.
      High correlations of scores on simulated computer adaptive testing (CAT) with the
      overall SCI-FI domain scores indicated excellent potential for CAT to accurately
      characterize functional profiles of adults with SCI. Overall, there was very
      little loss of measurement reliability or precision using CAT compared with the
      full item bank; however, there was some loss of reliability and precision at the
      lower and upper ranges of each scale, corresponding to regions where there were
      few questions in the item banks. CONCLUSIONS: Initial evaluation revealed that
      the SCI-FI achieved considerable breadth of coverage in each content domain and
      demonstrated acceptable psychometric properties. The use of CAT to administer the
      SCI-FI will minimize assessment burden, while allowing for the comprehensive
      assessment of the functional abilities of adults with SCI.

PMID- 22609632
TI  - Epigenomics of cancer - emerging new concepts.
AB  - The complexity of the mammalian genome is regulated by heritable epigenetic
      mechanisms, which provide the basis for differentiation, development and cellular
      homeostasis. These mechanisms act on the level of chromatin, by modifying DNA,
      histone proteins and nucleosome density/composition. During the last decade it
      became clear that cancer is defined by a variety of epigenetic changes, which
      occur in early stages of disease and parallel genetic mutations. With the advent
      of new technologies we are just starting to unravel the cancer epigenome and
      latest mechanistic findings provide the first clue as to how altered epigenetic
      patterns might occur in different cancers. Here we review latest findings on
      chromatin related mechanisms and hypothesize how their impairment might
      contribute to the altered epigenome of cancer cells.

PMID- 22609638
TI  - (De)localization and the mobility edges in a disordered double chain with long
      range intrachain correlation and short-range interchain correlation.
AB  - Correlation effects and phase transitions are central issues in current studies
      on disordered systems. In this paper, we study the electronic properties of a
      disordered double chain with long-range intrachain correlation and short-range
      interchain correlation. Based on detailed numerical calculations, finite size
      scaling analysis and empirical analytical calculations, we obtain a phase diagram
      containing rich physics due to the interplay among the disorder, short-range and
      long-range correlations. Besides the long-range correlation induced localization
      delocalization transitions, we find both first-order and second-order quantum
      phase transitions on changing the short-range correlation. Interestingly, the
      localization may be suppressed by increasing the disorder strength in some
      parameter regime and the 'anti-correlation' leads to the most delocalized state.
      Our studies shine some light on the mechanism of the charge transport in DNA
      molecules, where both types of correlated disorders are present.

PMID- 22609636
TI  - Increased plasma levels of soluble vascular endothelial growth factor receptor 1
      (sFlt-1) in women by moderate exercise and increased plasma levels of vascular
      endothelial growth factor in overweight/obese women.
AB  - The incidence of breast cancer is increasing worldwide, and this seems to be
      related to an increase in lifestyle risk factors, including physical inactivity
      and overweight/obesity. We have reported previously that exercise induced a
      circulating angiostatic phenotype characterized by increased soluble fms-like
      tyrosine kinase-1 (sFlt-1) and endostatin and decreased unbound vascular
      endothelial growth factor (VEGF) in men. However, there are no data on women. The
      present study determines the following: (a) whether moderate exercise increased
      sFlt-1 and endostatin and decreased unbound VEGF in the circulation of adult
      female volunteers and (b) whether overweight/obese women have a higher plasma
      level of unbound VEGF than lean women. A total of 72 African American and White
      adult women volunteers ranging in age from 18 to 44 years were enrolled in the
      exercise study. All the participants walked on a treadmill for 30 min at a
      moderate intensity (55-59% heart rate reserve), and oxygen consumption (VO(2))
      was quantified utilizing a metabolic cart. We obtained blood samples before and
      immediately after exercise from 63 participants. ELISA assays showed that the
      plasma levels of sFlt-1 were 67.8+/-3.7 pg/ml immediately after exercise (30
      min), significantly higher than the basal levels, 54.5+/-3.3 pg/ml, before
      exercise (P<0.01; n=63). There was no significant difference in the % increase in
      the sFlt-1 levels after exercise between African American and White (P=0.533)
      women or between lean and overweight/obese women (P=0.892). There was no
      significant difference in the plasma levels of unbound VEGF (35.28+/-5.47 vs.
      35.23+/-4.96 pg/ml; P=0.99) or endostatin (111.12+/-5.48 vs. 115.45+/-7.15 ng/ml;
      P=0.63) before and after exercise. The basal plasma levels of unbound VEGF in
      overweight/obese women were 52.26+/-9.6 pg/ml, significantly higher than the
      basal levels of unbound VEGF in lean women, 27.34+/-4.99 pg/ml (P<0.05). The
      results support our hypothesis that exercise-induced plasma levels of sFlt-1
      could be an important clinical biomarker to explore the mechanisms of exercise
      training in reducing the progression of breast cancer and that VEGF is an
      important biomarker in obesity and obesity-related cancer progression.

PMID- 22609637
TI  - Occupational solvent exposure, genetic variation in immune genes, and the risk
      for non-Hodgkin lymphoma.
AB  - Solvent exposure has been inconsistently linked to the risk for non-Hodgkin
      lymphoma (NHL). The aim of this study was to determine whether the association is
      modified by genetic variation in immune genes. A population-based case-control
      study involving 601 incident cases of NHL and 717 controls was carried out in
      1996-2000 among women from Connecticut. Thirty single nucleotide polymorphisms in
      17 immune genes were examined in relation to the associations between exposure to
      various solvents and the risk for NHL. The study found that polymorphism in
      interleukin 10 (IL10; rs1800890) modified the association between occupational
      exposure to organic solvents and the risk for diffuse large B-cell lymphoma
      (P(for interaction)=0.0058). The results remained statistically significant after
      adjustment for false discovery rate. Compared with women who were never
      occupationally exposed to any organic solvents, women who were exposed to organic
      solvents at least once had a significantly increased risk for diffuse large B
      cell lymphoma if they carried the IL10 (rs1800890) TT genotype (odds ratio=3.31,
      95% confidence interval: 1.80-6.08), but not if they carried the AT/AA genotype
      (odds ratio=1.14, 95% confidence interval: 0.72-1.79). No significant
      interactions were observed for other immune gene single nucleotide polymorphisms
      and various solvents in relation to NHL overall and its major subtypes. The study
      provided preliminary evidence supporting a role of immune gene variations in
      modifying the association between occupational solvent exposure and the risk for
      NHL.

PMID- 22609640
TI  - Cytotoxicity of monodispersed chitosan nanoparticles against the Caco-2 cells.
AB  - Published toxicology data on chitosan nanoparticles (NP) often lack direct
      correlation to the in situ size and surface characteristics of the nanoparticles,
      and the repeated NP assaults as experienced in chronic use. The aim of this paper
      was to breach these gaps. Chitosan nanoparticles synthesized by spinning disc
      processing were characterised for size and zeta potential in HBSS and EMEM at pHs
      6.0 and 7.4. Cytotoxicity against the Caco-2 cells was evaluated by measuring the
      changes in intracellular mitochondrial dehydrogenase activity, TEER and sodium
      fluorescein transport data and cell morphology. Cellular uptake of NP was
      observed under the confocal microscope. Contrary to established norms, the
      collective data suggest that the in vitro cytotoxicity of NP against the Caco-2
      cells was less influenced by positive surface charges than by the particle size.
      Particle size was in turn determined by the pH of the medium in which the NP was
      dispersed, with the mean size ranging from 25 to 333 nm. At exposure
      concentration of 0.1%, NP of 25 +/- 7 nm (zeta potential 5.3 +/- 2.8 mV) was
      internalised by the Caco-2 cells, and the particles were observed to inflict
      extensive damage to the intracellular organelles. Concurrently, the transport of
      materials along the paracellular pathway was significantly facilitated. The Caco
      2 cells were, however, capable of recovering from such assaults 5 days following
      NP removal, although a repeat NP exposure was observed to produce similar effects
      to the 1st exposure, with the cells exhibiting comparable resiliency to the 2nd
      assault.

PMID- 22609641
TI  - Evaluation of the sensitizing potential of antibiotics in vitro using the human
      cell lines THP-1 and MUTZ-LC and primary monocyte-derived dendritic cells.
AB  - Since the 7th amendment to the EU cosmetics directive foresees a complete ban on
      animal testing, alternative in vitro methods have been established to evaluate
      the sensitizing potential of small molecular weight compounds. To find out
      whether these novel in vitro assays are also capable to predict the sensitizing
      potential of small molecular weight drugs, model compounds such as beta-lactams
      and sulfonamides - which are the most frequent cause of adverse drug reactions -
      were co-incubated with THP-1, MUTZ-LC, or primary monocyte-derived dendritic
      cells for 48 h and subsequent expression of selected marker genes (IL-8, IL
      1beta, CES1, NQO1, GCLM, PIR and TRIM16) was studied by real time PCR.
      Benzylpenicillin and phenoxymethylpenicillin were recognized as sensitizing
      compounds because they are capable to induce the mRNA expression of these genes
      in moDCs and, except for IL-8, in THP-1 cells but not in MUTZ-LC. Ampicillin
      stimulated the expression of some marker genes in moDCs and THP-1 cells. SMX did
      not affect the expression of these genes in THP-1, however, in moDCs, at least
      PIR was enhanced and there was an increase of the release of IL-8. These data
      reveal that novel in vitro DC based assays might play a role in the evaluation of
      the allergenic potential of novel drug compounds, but these systems seem to lack
      the ability to detect the sensitizing potential of prohaptens that require
      metabolic activation prior to sensitization and moDCs seem to be superior with
      regard to the sensitivity compared with THP-1 and MUTZ-3 cell lines.

PMID- 22609642
TI  - Tai chi and chronic pain.
AB  - In the last 2 decades, a growing body of research aimed at investigating the
      health benefits of Tai Chi in various chronic health conditions has been
      recognized in the literature. This article reviewed the history, the philosophy,
      and the evidence for the role of Tai Chi in a few selected chronic pain
      conditions. The ancient health art of Tai Chi contributes to chronic pain
      management in 3 major areas: adaptive exercise, mind-body interaction, and
      meditation. Trials examining the health benefit of Tai Chi in chronic pain
      conditions are mostly low quality. Only 5 pain conditions were reviewed:
      osteoarthritis, fibromyalgia, rheumatoid arthritis, low back pain, and headache.
      Of these, Tai Chi seems to be an effective intervention in osteoarthritis, low
      back pain, and fibromyalgia. The limitations of the Tai Chi study design and
      suggestions for the direction of future research are also discussed.

PMID- 22609643
TI  - Real-time evaluation of diffusion of the local anesthetic solution during
      peribulbar block using ultrasound imaging and clinical correlates of diffusion.
AB  - BACKGROUND AND OBJECTIVES: The aims of this prospective observational study were
      to assess the incidence of intraconal spread during peribulbar (extraconal)
      anesthesia by real-time ultrasound imaging of the retro-orbital compartment and
      to determine whether a complete sensory and motor block (with akinesia) of the
      eye is directly related to the intraconal spread. METHODS: Ultrasound imaging was
      performed in 100 patients who underwent a surgical procedure on the posterior
      segment of the eye. All patients received a peribulbar block using the
      inferolateral approach. Once the needle was in place, a linear ultrasound
      transducer was placed over the eyelid and the spread of local anesthetics was
      assessed during the injection (real time). Akinesia was assessed by a blinded
      observer 10 minutes after block placement. The incidence of intraconal spread and
      its correlation with a complete akinesia was measured. RESULTS: The overall block
      failure rate was 28% in terms of akinesia, and the rate of rescue blocks was 20%.
      Clear intraconal spread during injection of the local anesthetic mixture could be
      detected with ultrasound imaging in 61 of 100 patients. The positive predictive
      value for successful block when intraconal spread was detected was 98% (95%
      confidence interval, 91%-100%). The association between clear and no evidence of
      intraconal spread and effective block was statistically significant (chi test, P
      < 0.001). CONCLUSIONS: Ultrasound imaging provides information of local
      anesthetic spread within the retro-orbital space, which might assist in the
      prediction of block success.

PMID- 22609644
TI  - Hemodynamic profile of target-controlled spinal anesthesia compared with 2 target
      controlled general anesthesia techniques in elderly patients with cardiac
      comorbidities.
AB  - BACKGROUND AND OBJECTIVES: The impact of anesthesia techniques in patients
      experiencing hip fracture is controversial. This study compares the effects on
      blood pressure of 3 anesthesia techniques that are considered safe for the
      elderly. METHODS: Forty-five patients older than 75 years, with American Society
      of Anesthesiologists physical status III or IV, with cardiac comorbidities, and
      undergoing surgery for hip fracture, were randomized to receive continuous spinal
      anesthesia (CSA), propofol target-controlled infusion (TCI), or sevoflurane
      (SEVO). In CSA patients, a T10 metameric level target was achieved by titration
      of 2.5 mg of bupivacaine boluses. In patients on TCI and SEVO, a bispectral value
      target of around 50 guided the concentration of propofol or sevoflurane.
      Analgesia in the TCI and SEVO groups was provided with remifentanil. Hypotension
      was defined as a 30% decrease in mean arterial pressure and was treated with an
      intravenous bolus of ephedrine. RESULTS: The number of hypotension episodes was
      lower in the CSA group: 0 (range, 0-6) versus 11.5 (range, 1-25) in the TCI group
      and 10 (range, 1-23) in the SEVO group (P < 0.001). Both TCI and SEVO patients
      needed more ephedrine compared with CSA patients (30.5 [15.5], 26 [23], and 1.5
      [2.5] mg, respectively, P < 0.001). The maximal decrease in mean arterial
      pressure was lower in the CSA group (26% [17%]) compared with that in the TCI
      group (47% [8%]) and the SEVO group (46% [12%]; P < 0.001). CONCLUSIONS: In
      elderly patients, spinal anesthesia using titrated doses of bupivacaine provided
      better blood pressure stability than propofol or sevoflurane anesthesia.

PMID- 22609645
TI  - Dose-ranging effects of intrathecal epinephrine on anesthesia/analgesia: a meta
      analysis and metaregression of randomized controlled trials.
AB  - BACKGROUND AND OBJECTIVES: Intrathecal epinephrine has been examined by clinical
      studies, but its effects on analgesia/anesthesia outcomes as well as on
      undesirable adverse effects is not clearly defined. The objective of this study
      was to examine the effects of intrathecal epinephrine on intrathecal
      anesthesia/analgesia. METHODS: We performed a meta-analysis, using a random
      effects model. Effects of intrathecal epinephrine dose were evaluated by pooling
      studies into 3 dosage groups: low (1-100 ug), intermediate (101-200 ug), and high
      (>=200 ug). Metaregression analyses were also performed to examine the presence
      of a linear association between intrathecal epinephrine dose and effect size on
      evaluated outcomes. RESULTS: Twenty-four randomized clinical trials with 1,271
      subjects were included. The mean (95% confidence interval [CI]) combined effects
      favored intrathecal epinephrine over placebo for duration of analgesia, 27.0 mins
      (20.8-33.3 mins); sensory, 35.0 mins (22.8-47.3 mins); and motor block, 32.2 mins
      (26.2-38.2 mins). The incidence of hypotension and postoperative nausea and
      vomiting (PONV) was greater for the low dose (1-100 ug) intrathecal epinephrine
      group compared with placebo (odds ratios [95% CI], 3.0 [1.5-5.9] and 2.7 [1.5
      4.8], respectively). A greater incidence of hypotension and PONV was not detected
      for the intermediate-dose group (101-200 ug): odds ratios (95% CI) of 0.9 (0.5
      1.7) and 1.6 (0.6-4.6), respectively. CONCLUSIONS: Intrathecal epinephrine has
      dose-dependent clinical and adverse effects. Doses of 100 ug or less prolonged
      sensory and motor block duration but were associated with greater incidence of
      hypotension or PONV. Intrathecal epinephrine doses greater than 100 ug prolonged
      sensory and motor block and were not associated with greater incidence of
      hypotension and PONV.

PMID- 22609646
TI  - Injection inside the paraneural sheath of the sciatic nerve: direct comparison
      among ultrasound imaging, macroscopic anatomy, and histologic analysis.
AB  - BACKGROUND AND OBJECTIVES: There exists little anatomic knowledge regarding the
      structure and sonographic features of the sheath enveloping the sciatic nerve in
      the popliteal fossa. We investigated the spread of an injection inside the sheath
      to (1) determine whether the sheath is a structure distinct from the nerve or
      part of the epineurium and (2) to develop an ultrasound-guided injection
      technique. METHODS: Using gross dissection, ultrasound examination, and
      histologic study, we characterized the tissue layer surrounding the sciatic nerve
      in the popliteal fossa of 28 unembalmed cadaver legs. RESULTS: Grossly, we
      identified a thin, transparent, and fragile tissue layer surrounding the
      epineurium. Sonographically, this layer was identified with injectate as a
      hyperechoic layer detaching from the surface of the sciatic nerve.
      Histologically, the sheath was seen as a multilayered circular fascia as part of
      the paraneural tissue. An injection of 10 mL inside the sheath spread 10 to 15 cm
      closely along the nerve, however, not completely circumferential, compared with 5
      to 6 cm if the injection was outside the sheath. Characteristics of the
      ultrasound-guided injection technique are described. CONCLUSIONS: There is a
      distinct tissue layer surrounding the popliteal sciatic nerve as a paraneural
      sheath that has distinct gross anatomic, histologic, and sonographic features.
      This sheath may have implications for regional anesthesia involving the popliteal
      sciatic nerve. We suggest that the ultrasound-guided injection technique
      described here could be used in future clinical studies investigating the
      importance of the paraneural sheath.

PMID- 22609647
TI  - Integrated thermophilic submerged aerobic membrane bioreactor and electrochemical
      oxidation for pulp and paper effluent treatment--towards system closure.
AB  - A novel integrated thermophilic submerged aerobic membrane bioreactor (TSAMBR)
      and electrochemical oxidation (EO) technology was developed for thermomechanical
      pulping pressate treatment with the aim of system closure. The TSAMBR was able to
      achieve a chemical oxygen demand (COD) removal efficiency of 88.6 +/- 1.9-92.3 +/
      0.7% under the organic loading rate of 2.76 +/- 0.13-3.98 +/- 0.23 kg COD/(m(3)
      d). An optimal hydraulic retention time (HRT) of 1.1 +/- 0.1d was identified for
      COD removal. Cake formation was identified as the dominant mechanism of membrane
      fouling. The EO of the TSAMBR permeate was performed using a Ti/SnO(2)-Sb(2)O(5)
      IrO(2) electrode. After 6-h EO, a complete decolourization was achieved and the
      COD removal efficiency was increased to 96.2 +/- 1.2-98.2 +/- 0.3%. The high
      quality effluent produced by the TSAMBR-EO system can be reused as process water
      for system closure in pulp and paper mill.

PMID- 22609648
TI  - Effects of yeast-originating polymeric compounds on ethanol pervaporation.
AB  - During ethanol fermentation with in situ pervaporation, membrane fouling might
      occur due to polymers originating from yeast cell lysis. The aim of this study
      was to evaluate the influence of yeast cellular polymers on pervaporative
      membrane performance. Lipids were identified as the most detrimental components
      among these cellular polymers causing 50% and 33% flux decrease in
      polydimethylsiloxane (PDMS) and polyoctylmethylsiloxane (POMS) membranes,
      respectively. This fouling was irreversible and might be due to hydrophobic
      interactions between lipids and membranes resulting in high lipid adsorption on
      membrane surface. The relatively hydrophobic model protein BSA also contributed
      to flux decrease in PDMS membrane but RNA and the model polysaccharide glycogen
      did not. The PDMS membrane selectivity for ethanol/water remained ~4.5 in all
      cases. All the cellular components decreased the water flux through the POMS
      membrane. However, the ethanol flux through the membrane was not altered very
      much, resulting in increased membrane selectivity.

PMID- 22609649
TI  - A spectroscopic study for understanding the speciation of Cr on palm shell based
      adsorbents and their application for the remediation of chrome plating effluents.
AB  - Palm shell based adsorbents prepared under five different thermochemical
      conditions have been shown to be quite effective for removal of chromium (III and
      VI) from aqueous solutions. X-ray photoelectron spectroscopy (XPS) and Fourier
      Transform Infrared Spectroscopy (FT-IR) have been used to determine information
      about the speciation and binding of chromium on the adsorbents under study. X-ray
      photoelectron spectroscopy (XPS) studies indicate that oxidation of lignin
      moieties takes place concurrently to Cr(VI) reduction and leads to the formation
      of hydroxyl and carboxyl functions. The maximum adsorption capacity for
      hexavalent chromium was found to be about 313 mg/g in an acidic medium using
      PAPSP. This is comparable to other natural substrates and ordinary adsorbents.
      The efficacy of the adsorbents under study to remove chromium from plating waste
      water has been demonstrated.

PMID- 22609650
TI  - Oil recovery from refinery oily sludge using a rhamnolipid biosurfactant
      producing Pseudomonas.
AB  - In this study, a rhamnolipid biosurfactant-producing strain, Pseudomonas
      aeruginosa F-2, was used to recover oil from refinery oily sludge in laboratory
      and pilot-scale experiments. The optimum values of carbon to nitrogen ratio,
      temperature, sludge-water ratio and inoculum size for oil recovery were
      determined as 10, 35  degrees C, 1:4 and 4%, respectively. An oil recovery of up
      to 91.5% was obtained with the equipping of draft tubes during the field pilot
      scale studies. The results showed that strain F-2 has the potential for
      industrial applications and may be used in oil recovery from oily sludge.

PMID- 22609651
TI  - Hydrolysis of organosolv wheat pulp in formic acid at high temperature for
      glucose production.
AB  - Organosolv methods can be used to delignify lignocellulosic crop residues for
      pulp production or to pretreat them prior to enzymatic hydrolysis for bioethanol
      production. In this study, organic solvent was used as an acidic hydrolysis
      catalyst to produce glucose. Hydrolysis experiments were carried out in 5-20%
      formic acid at 180-220  degrees C. Wheat straw pulp delignified with a
      formicodeliTM method was used as a raw material. It was found that glucose yields
      from pulp are significantly higher than yields from microcrystalline cellulose, a
      model component for cellulose hydrolysis. The results indicate that cellulose
      hydrolysis of real fibers takes place more selectively to glucose than hydrolysis
      of microcrystalline cellulose particles does. The effect of the particle size on
      pulp hydrolysis was investigated, the crystallinity of hydrolyzed pulp was
      measured by XRD analysis, and the product distribution and its influence on the
      process was discussed.

PMID- 22609652
TI  - Combined effect of pelleting and pretreatment on enzymatic hydrolysis of
      switchgrass.
AB  - Switchgrass was pelleted to evaluate the effect of densification on acidic and
      alkaline pretreatment efficacy. Bulk density and durability of pellets were 724
      kg/m(3) and 95%, respectively. Ground switchgrass (D(90) = 21.7 mm) was further
      ground to a fine power (D(90) = 0.5mm) in the pellet mill prior to densification.
      This grinding increased enzymatic hydrolyzate glucose yields of non-pretreated
      materials by 210%. Pelleting had no adverse impact on dilute acid pretreatment
      efficacy. Grinding and pelleting increased hydrolyzate glucose yields of
      switchgrass pretreated by soaking in aqueous ammonia (SAA) by 37%. Xylose yields
      from SAA-pretreated switchgrass pellets were 42% higher than those from the
      original biomass. Increases in sugar yields from SAA-pretreated pelleted biomass
      are attributed to grinding and heating of biomass during the pelleting process.
      Potential transportation, storage, and handling benefits of biomass pelleting may
      be achieved without negatively affecting the downstream processing steps of
      pretreatment or enzymatic hydrolysis.

PMID- 22609653
TI  - Methane potential of sterilized solid slaughterhouse wastes.
AB  - The aim of the current study was to determine chemical composition and methane
      potential of Category 2 and 3 solid slaughterhouse wastes rendering products
      (SSHWRP) viz. melt, decanter sludge, meat and bone meal (MBM), technical fat and
      flotation sludge from wastewater treatment. Chemical analyses showed that SSHWRP
      were high in protein and lipids with total solids (TS) content of 96-99%. Methane
      yields of the SSHWRP were between 390 and 978 m(3) CH(4)/t volatile solids
      (VS)(added). Based on batch experiments, anaerobic digestion of SSHWRP from the
      dry rendering process could recover 4.6 times more primary energy than the energy
      required for the rendering process. Estonia has technological capacity to
      sterilize all the produced Category 2 and 3 solid slaughterhouse wastes (SSHW)
      and if separated from Category 1 animal by-products (ABP), it could be further
      utilized as energy rich input material for anaerobic digestion.

PMID- 22609654
TI  - Hydraulic characteristics and their effects on working performance of
      compartmentalized anaerobic reactor.
AB  - The compartmentalized anaerobic reactor (CAR) is a patent novel high-rate reactor
      and shows a great potential for its application. The hydraulic characteristics
      and their effects on the working performance of CAR were investigated. The flow
      pattern tended to plug flow at normal organic loading rate (OLR) and completely
      mixed flow at high OLRs. The relation of hydraulic dead space (HDS or V(h)) with
      hydraulic loading rate (HLR or L) and biogas production rate (BPR or G) was V(h)
      = 3.75 L + 0.19 G-9.47. The hydraulic efficiency of CAR was good or near to good.
      Both HLR and BPR had significant effects on the hydraulic efficiency, but their
      effect became less at super-high OLR. They also had a slight influence on the
      effective volume ratios of CAR, but the influence of BPR almost disappeared at
      super-high OLR. The good working performance of CAR was ascribed to the improved
      reactor configuration.

PMID- 22609655
TI  - Preparation of biodiesel from rice bran fatty acids catalyzed by heterogeneous
      cesium-exchanged 12-tungstophosphoric acids.
AB  - Biodiesel synthesis from rice bran fatty acids (RBFA) was carried out using
      cesium exchanged 12-tungstophosphoric acid (TPA) catalysts. The physico-chemical
      properties of the catalysts were derived from X-ray diffraction (XRD), Fourier
      transform infrared (FTIR), temperature programmed desorption (TPD) of NH(3) and
      scanning electron microscopy (SEM). The characterization techniques revealed that
      the Keggin structure of TPA remained intact as Cs replaced protons. The partial
      exchange of Cs for protons resulted in an increase in acidity and the catalysts
      with one Cs(+) (Cs(1)H(2)PW(12)O(40)) showed highest acidity. Under optimized
      conditions about 92% conversion of RBFA was obtained. The catalyst was reused for
      five times and retained of its original activity. Pseudo-first order model was
      applied to correlate the experimental kinetic data. Modified tungstophosphoric
      acids are efficient solid acid catalysts for the synthesis of biodiesel from the
      oils containing high FFA.

PMID- 22609656
TI  - Optimization of levulinic acid from lignocellulosic biomass using a new hybrid
      catalyst.
AB  - Conversion of glucose, empty fruit bunch (efb) and kenaf to levulinic acid over a
      new hybrid catalyst has been investigated in this study. The characterization and
      catalytic performance results revealed that the physico-chemical properties of
      the new hybrid catalyst comprised of chromium chloride and HY zeolite increased
      the levulinic acid production from glucose compared to the parent catalysts.
      Optimization of the glucose conversion process using two level full factorial
      designs (2(3)) with two center points reported 55.2% of levulinic acid yield at
      145.2  degrees C, 146.7 min and 12.0% of reaction temperature, reaction time and
      catalyst loading, respectively. Subsequently, the potential of efb and kenaf for
      producing levulinic acid at the optimum conditions was established after 53.2%
      and 66.1% of efficiencies were reported. The observation suggests that the hybrid
      catalyst has a potential to be used in biomass conversion to levulinic acid.

PMID- 22609657
TI  - Simultaneous biodegradation of Ni-citrate complexes and removal of nickel from
      solutions by Pseudomonas alcaliphila.
AB  - The objective of this study was to study the simultaneous biodegradation of Ni
      citrate complexes and removal of Ni from solutions by Pseudomonas alcaliphila.
      Adding excess citrate to 1:1 Ni-citrate complexes promoted the degradation of the
      complexes and removal of Ni. The alkaline pH generated by the metabolism of
      excess citrate caused partial dissociation of citrate from the Ni-citrate
      complexes, allowing degradation, and the released Ni was removed through
      bioaccumulation and precipitation. Addition of Fe(3+) enhanced the degradation of
      Ni-citrate complexes and removal of Ni from solutions. The displacement of Ni
      from recalcitrant Ni-citrate complexes by Fe(3+) and subsequent biodegradation of
      the degradable Fe(III)-citrate complex resulted in complete metabolism of
      citrate. The almost complete removal of Ni (>98%) can be attributed to the
      combination of coprecipitation with Fe(3+), bioaccumulation and precipitation. P.
      alcaliphila potentially could be applied in the treatment of effluent containing
      Ni-citrate complexes.

PMID- 22609658
TI  - A modified method for calculating practical ethanol yield at high lignocellulosic
      solids content and high ethanol titer.
AB  - A modified method for calculating practical ethanol yield in the simultaneous
      saccharification and fermentation (SSF) at high lignocellulosic solids content
      and high ethanol titer is proposed considering the liquid volume change caused by
      high titer ethanol generation and the water consumed during cellulose
      degradation. This modified method was applied to determine the practical ethanol
      yields of several practical SSF operations and the results compared to those
      using the conventional method. The results show that the liquid volume increase
      with ethanol formation during SSF was approximately five times greater than the
      volume decrease duo to water consumption during cellulose degradation.
      Furthermore, the practical ethanol yields calculating using traditional method
      were underestimated and the underestimated errors increased with the increasing
      ethanol titer. The present work may provide a convenient and accurate method for
      calculating practical ethanol yield in a high solids and high ethanol titer SSF
      systems.

PMID- 22609659
TI  - Degradation of algal organic matter using microbial fuel cells and its
      association with trihalomethane precursor removal.
AB  - In order to provide an alternative for removal of algal organic matter (AOM)
      produced during algal blooms in aquatic environment, microbial fuel cell (MFC)
      was used to study AOM degradation and its association with THM precursor removal.
      The chemical oxygen demand (COD) removals in MFCs were 81 +/- 6% and 73 +/- 3%
      for AOM from Microcystis aeruginosa (AOM(M)) and Chlorella vulgaris (AOM(C)),
      respectively. THM precursor was also effectively degraded (AOM(M) 85 +/- 2%,
      AOM(C) 72 +/- 4%). The major AOM components (proteins, lipids, and carbohydrates)
      were obviously removed in MFCs. The contribution of each component to the THM
      formation potential (THMFP) was obtained based on calculation. The THMFP produced
      from soluble microbial products was very low. If the energy input during
      operation process was not considered, MFCs treatment could recover electrical
      energy of 0.29 +/- 0.02 kWh/kg COD (AOM(M)) and 0.35 +/- 0.06 kWh/kg COD
      (AOM(C)).

PMID- 22609660
TI  - A terracotta bio-battery.
AB  - Terracotta pots were converted into simple, single chamber, air-cathode bio
      batteries. This bio-battery design used a graphite-felt anode and a conductive
      graphite coating without added catalyst on the exterior as a cathode. Bacteria
      enriched from river sediment served as the anode catalyst. These batteries gave
      an average OCV of 0.56 V +/- 0.02, a Coulombic efficiency of 21 +/- 5%, and a
      peak power of 1.06 mW +/- 0.01(33.13 mW/m(2)). Stable current was also produced
      when the batteries were operated with hay extract in salt solution. The bacterial
      community on the anode of the batteries was tested for air tolerance and
      desiccation resistance over a period ranging from 2 days to 2 weeks. The results
      showed that the anode community could survive complete drying of the electrolyte
      for several days. These data support the further development of this technology
      as a potential power source for LED-based lighting in off-grid, rural
      communities.

PMID- 22609661
TI  - Improving secondary sludge biodegradability using free nitrous acid treatment.
AB  - This study presents a novel strategy based on free nitrous acid (FNA) treatment
      to improve the biodegradability of secondary sludge. Several experiments were
      conducted to demonstrate the biocidal effect of FNA on activated sludge. The
      viable fraction as well as the biological activity of the biomass decreased
      significantly after 8-48 h treatment with FNA. The biodegradability of the FNA
      treated sludge was compared to that of the same sludge without FNA treatment by
      aerobically digesting these sludges with a full-scale activated sludge for 14 and
      6 days respectively. Ninety percent of the FNA treated biomass was consumed
      during the 14-day aerobic digestion compared to 41% achieved with the untreated
      biomass. During the 6-day aerobic digestion, 50% of the FNA-treated sludge was
      degraded. The results indicate that FNA treatment substantially increases sludge
      biodegradability.

PMID- 22609662
TI  - Structural transformation of hemicelluloses and lignin from triploid poplar
      during acid-pretreatment based biorefinery process.
AB  - In order to understand the behaviors of hemicelluloses and lignin under the given
      acidic conditions with increasing severity, the structural characteristics were
      elucidated in detail by both wet chemistry methods and spectroscopic analyses in
      this study. Although acidic pretreatment significantly hydrolyzed the glycosidic
      linkages in xylan backbone and then reduced the molecular weight of xylan from
      89,600 to 19,630 g/mol, a slightly increased amount of glucuronic acid was
      observed, probably attributing to the maintenance of ester bonds. The serious
      structural variation occurred in lignin macromolecule was evidenced by the
      extensive degradation of beta-O-4 ether linkages and resinol substructure,
      together with the changes in the ratios of the three monolignols in ester-bond,
      ether-bond and non-condensed phenolic compounds. At the most severity, obvious
      condensation reactions introduced the clear shift of C(2) and C(5) correlations
      and the absence of C(6) correlation in guaiacyl units by 2D HSQC analysis.

PMID- 22609663
TI  - Influence of a glass wool hot vapour filter on yields and properties of bio-oil
      derived from rapid pyrolysis of paddy residues.
AB  - This article reports experimental results of rapid or fast pyrolysis of rice
      straw (RS) and rice husk (RH) in a fluidised-bed reactor unit incorporated with a
      hot vapour filter. The objective of this research was to investigate the effects
      of pyrolysis temperatures and the use of glass wool hot vapour filtration on
      pyrolysis products. The results showed that the optimum pyrolysis temperatures
      for RS and RH were 405 and 452  degrees C, which gave maximum bio-oil yields of
      54.1 and 57.1 wt.% on dry biomass basis, respectively. The use of the hot filter
      led to a reduction of 4-7 wt.% bio-oil yield. Nevertheless, the glass wool hot
      filtered bio-oils appeared to have better quality in terms of initial viscosity,
      solids content and ash content than the non-filtered ones.

PMID- 22609664
TI  - Characterization of a bio-oil from pyrolysis of rice husk by detailed
      compositional analysis and structural investigation of lignin.
AB  - Detailed compositional analysis of a bio-oil (BO) from pyrolysis of rice husk was
      carried out. The BO was extracted sequentially with n-hexane, CCl(4), CS(2),
      benzene and CH(2)Cl(2). In total, 167 organic species were identified with GC/MS
      in the extracts and classified into alkanes, alcohols, hydroxybenzenes,
      alkoxybenzenes, dioxolanes, aldehydes, ketones, carboxylic acids, esters,
      nitrogen-containing organic compounds and other species. The benzene ring
      containing species (BRCCs) were attributed to the degradation of lignin while
      most of the rests were derived from the degradation of cellulose and
      hemicellulose. Along with guaiacyl and p-hydroxyphenyl units as the main
      components, a new type of linkage was suggested, i.e., C(ar)-CH(2)-C(ar) in 4,4'
      methylenebis(2,6-dimethoxyphenol). Based on the species identified, a possible
      macromolecular structure of the lignin and the mechanism for its pyrolysis are
      proposed. The BO was also extracted with petroleum ether in ca. 17.8% of the
      extract yield and about 82.1% of the extracted components are BRCCs.

PMID- 22609665
TI  - Physical and chemical characteristics of products from the torrefaction of yellow
      poplar (Liriodendron tulipifera).
AB  - We investigated the characteristics of torrefied yellow poplar (Liriodendron
      tulipifera) depending on reaction time (30 min) and temperature (240-280  degrees
      C). The thermogravimetric, grindability and calorific value of torrefied biomass
      were analyzed. As the torrefaction temperature increased, the carbon content of
      torrefied biomass increased from 49.50% to 54.42%, while the hydrogen and oxygen
      contents decreased from 6.09% to 5.65% and 28.71% to 26.61%, respectively. The
      highest calorific value was 1233 kJ/kg when torrefaction was performed at 280 
      degrees C for 30 min. An overall increase in energy density and decrease in mass
      and energy yield was observed with the increase in torrefaction temperature. The
      analysis of thermal decomposition demonstrated that the hemicelluloses contained
      in torrefied biomass decreased with increasing torrefaction temperature, whereas
      cellulose and lignin were only slightly affected. The grindability of torrefied
      biomass was significantly improved when torrefaction was performed at high
      temperature. Torrefaction of yellow poplar improved the chemical and physical
      fuel properties of the biomass.

PMID- 22609666
TI  - Initial-rate based method for estimating the maximum heterotrophic growth rate
      parameter (MUHmax).
AB  - Currently, the method most used for measuring the maximum specific growth rate
      (MU(Hmax)) of heterotrophic biomass is by respirometry, using growth batch tests
      performed at high food/microorganism ratio. No other technique has been
      suggested, although the former approach was criticized for providing kinetic
      constants that could be unrepresentative of the original biomass. An alternative
      method (seed-increments) is proposed, which relies on measuring the initial rates
      of respiration (r(O2)(_ini)) at different seeding levels, in a single batch, and
      in the presence of excess readily biodegradable substrate (S(S)). The ASM1-based
      underlying equations were developed, which showed that MU(Hmax) could be
      estimated through the slope of the linear function of r(O2)(_ini).(V(WW)+v(ML))
      vs v(ML) (volume of mixed liquor inoculum); V(WW) represent the wastewater volume
      added. The procedure was tested, being easy to apply; the postulated linearity
      was constantly observed and the method is claimed to measure the characteristics
      of the biomass of interest.

PMID- 22609667
TI  - Microwave-assisted direct liquefaction of Ulva prolifera for bio-oil production
      by acid catalysis.
AB  - Production of bio-oil by microwave-assisted direct liquefaction (MADL) of Ulva
      prolifera was investigated, and the bio-oil was analyzed by elementary analysis,
      Fourier transform infrared spectroscopic analysis (FT-IR), and gas chromatography
      mass spectrometry (GC-MS). The results indicate that the liquefaction yield is
      influenced by the microwave power, liquefaction temperature, liquefaction time,
      catalyst content, solvent-to-feedstock ratio and moisture content. The maximum
      liquefaction yield of U. prolifera (moisture content of 8%) was 84.81%, which was
      obtained under microwave power of 600 W for 30 min at 180  degrees C with solvent
      to-feedstock ratio of 16:1 and 6% H(2)SO(4). The bio-oil was composed of
      benzenecarboxylic acid, diethyl phthalate, long-chain fatty acids (C(13) to
      C(18)), fatty acid methyl esters and water. The results suggest that U. prolifera
      is a viable eco-friendly, green feedstock substitute for biofuels and chemicals
      production.

PMID- 22609668
TI  - Preparation of a pH-sensitive polyacrylate amphiphilic copolymer and its
      application in cellulase immobilization.
AB  - P(MDB), a pH-sensitive and reversible water-soluble copolymer, was synthesized
      with methacrylic acid (MAA), 2-(dimethylamino) ethyl methacrylate (DMAEMA), and
      butyl methacrylate (BMA) and used as carrier for cellulase. The copolymer is
      insoluble between pH 2.5 and 4.1, and soluble below pH 2.5 or above 4.1. Its
      recovery in aqueous solution was 97.2% by adjusting its isoelectric point (pI) to
      3.1. Cellulase was covalently immobilized on P(MDB) with 1-ethyl-3-(3
      dimethyllaminopropyl) carbodiimide. Under optimized conditions, the activity
      yield of immobilized cellulase was 63.24% and its recovery was 96.8% by adjusting
      the pI to 3.5. Maximum activity of the immobilized cellulase was achieved at 60 
      degrees C (pH 5.0), while free cellulase exhibited maximum activity at 55 
      degrees C (pH 5.0). The immobilized cellulase retained 83.1% of its initial
      activity after repeated five cycles of hydrolysis reaction. P(MDB) is a promising
      carrier for immobilizing enzymes with high and low optimum pH due to its
      dissolving characteristics.

PMID- 22609669
TI  - Lignocellulose modifications by brown rot fungi and their effects, as
      pretreatments, on cellulolysis.
AB  - Brown rot fungi Gloeophyllum trabeum and Postia placenta were used to degrade
      aspen, spruce, or corn stover over 16 weeks. Decayed residues were saccharified
      using commercial cellulases or brown rot fungal extracts, loaded at equal but low
      endoglucanase titers. Saccharification was then repeated for high-yield samples
      using full strength commercial cellulases. Overall, brown rot pretreatments
      enhanced yields up to threefold when using either cellulase preparation. In the
      best case, aspen degraded 2 weeks by G. trabeum yielded 72% glucose-from
      cellulose, a 51% yield relative to original glucan. A follow-up trial with more
      frequent harvests showed similar patterns and demonstrated interplay between
      tissue modifications and saccharification. Hemicellulose and vanillic acid (G6)
      or vanillin (G4) lignin residues were good predictors of saccharification
      potential, the latter notable given lignin's potential active role in brown rot.
      Results show basic relationships over a brown rot time course and lend targets
      for controlling an applied bioconversion process.

PMID- 22609670
TI  - Effect of a milling pre-treatment on the enzymatic hydrolysis of carbohydrates in
      brewer's spent grain.
AB  - Millions of tonnes of brewer's spent grain (BSG) are annually produced worldwide
      as a by-product of the brewing industry. BSG has the potential to be a valuable
      source of food, chemicals and energy if cost-efficient fractionation methods can
      be developed. A 2-fold improvement in carbohydrate solubilisation could be
      achieved through the introduction of a milling step prior to enzymatic
      hydrolysis. Course and fine milled fractions were characterized by particle size
      distribution and light microscopy. Fine milling decreased particle size down to
      the micron level and this in turn improved the carbohydrate solubility yield by a
      multi-enzyme mixture from 23% up to 45%. Carbohydrate solubilisation could be
      further increased through the supplementation of this enzyme preparation with
      additional cellulases. The physical degradation caused by the milling also
      liberated soluble carbohydrates without the requirement of any enzymatic
      treatment.

PMID- 22609671
TI  - Mechanical and hydraulic properties of sludge deposit on sludge drying reed beds
      (SDRBs): influence of sludge characteristics and loading rates.
AB  - This work was designed to study the hydraulic properties of sludge deposit,
      focusing on the impact of operating conditions (i.e. loads and feeding
      frequencies) on air entrance (aerobic mineralization optimization) into the
      sludge deposit. The studied sludge deposits came from six 2m(2) pilot-scale SDRBs
      that had been in operation for 50 months with three different loads of 30, 50,
      and 70 kg of SSm(-2) y(-1). Two influents were assessed (i.e. activated sludge
      and septage) presenting different characteristics (i.e. pollutant contents,
      physical properties...). Two experimental approaches were employed based on
      establishing the water retention curve (capillary pressure versus volumetric
      water content) and the hydrotextural diagram to determine the hydraulic
      properties of sludge deposit. The study obtained valuable information for
      optimizing operating conditions, specifically for efficient management of loading
      frequency to optimize aerobic conditions within the sludge deposit.

PMID- 22609672
TI  - Batch anaerobic co-digestion of proteins and carbohydrates.
AB  - Batch anaerobic studies were conducted using five mixtures (M1-M5) of bovine
      serum albumin (BSA) and starch. The results showed that co-digestion of BSA and
      starch had a positive impact on the methane production. The highest methane
      production of 288 mL, the highest methane yield of 360 mL CH(4)/g COD(added), and
      the highest maximum methane production rate of 62 mL CH(4)/d were achieved for M4
      (20% BSA and 80% starch). Most of the particulate proteins (90%) as well as
      particulate carbohydrates (95%) were degraded in the first 3 days. The hydrolysis
      coefficients of particulate proteins and particulate carbohydrates ranged from
      0.65 to 1.01 d(-1) and from 0.53 to 1.06 d(-1), respectively. The highest methane
      production was achieved at C:N ratio of 12.8 for M4. For BSA only, propionic acid
      was the main volatile fatty acid (VFA), while for the starch only, butyric acid
      was the predominant VFA.

PMID- 22609673
TI  - Effect of carbon and nitrogen sources on photo-fermentative H2 production
      associated with nitrogenase, uptake hydrogenase activity, and PHB accumulation in
      Rhodobacter sphaeroides KD131.
AB  - During photo-fermentative H(2) production, the effects of carbon and nitrogen
      sources on nitrogenase and hydrogenase activity, poly-beta-hydroxybutyrate
      accumulation were investigated. In succinate/ammonium sulfate medium, H(2) was
      not detected for the first 6h because high ammonium concentration considerably
      reduced the nitrogenase activity to below 5 nmol/g-dcw/h. After 24h, 99% of the
      ammonium was consumed, and the nitrogenase activity increased to 296 nmol/g
      dcw/h, accelerating H(2) production. In contrast, the ammonium in
      succinate/glutamate medium was much less, which led to rapid H(2) production in
      the beginning. However, H(2) evolution was repressed over time by increased
      ammonium. In the presence of H(2), hydrogenase activity increased with time
      regardless of the nitrogen source, and consequently, H(2) production was reduced.
      Compared with succinate, H(2) production in acetate media was severely limited
      due to increased pH over 9. During extended cultivation, the PHB accumulated in
      acetate media was 7 times higher than in succinate media.

PMID- 22609674
TI  - A study on fluidized bed combustion characteristics of corncob in three different
      combustion modes.
AB  - This paper presents results obtained from corncob combustion in a pilot scale
      vortexing fluidized bed combustor (VFBC). Three combustion modes including direct
      combustion, staged combustion and flue gas recirculation (FGR) combustion were
      employed, and their combustion and pollutant emission characteristics were
      studied. In addition, the effects of combustion fraction and bed temperature on
      pollutant emission characteristics were investigated. The experimental results
      show that the combustion fractions vary with different combustion modes,
      resulting in different CO and NO emission characteristics. Staged and FGR
      combustions can reduce the NO emission concentration. Under similar working
      condition, NO concentration decreases by 30% in FGR mode, while 15% in staged
      mode compared with direct mode.

PMID- 22609675
TI  - Conversion of glucose into furans in the presence of AlCl3 in an ethanol-water
      solvent system.
AB  - Glucose was converted into furans (5-hydroxymethylfurfural and 5
      ethoxymethylfurfural) in the presence of AlCl(3) in an ethanol-water solvent
      system. The system showed high activity for the conversion of glucose into furans
      but low activity for the subsequent formation of LAs (levulinic acid and ethyl
      levulinate). High furans yield of 57% with low LAs yield of 11% can be obtained
      at 160  degrees C within 15 min. Glucose-based disaccharides (sucrose, maltose
      and cellobiose) and polysaccharides (starch but not cellulose) can also be
      converted to furans effectively under the same condition. AlCl(3) can be used to
      prepare furans from biomass-derived compounds in ethanol-water, a green solvent
      system.

PMID- 22609676
TI  - Zinc and cadmium biosorption by untreated and calcium-treated Macrocystis
      pyrifera in a batch system.
AB  - Zinc and cadmium can be efficiently removed from solutions using the brown algae,
      Macrocystis pyrifera. Treatment with CaCl(2) allowed stabilization of the
      biosorbent. The maximum biosorption capacities in mono-component systems were
      0.91 mmol g(-1) and 0.89 mmol g(-1) and the Langmuir affinity coefficients were
      1.76 L mmol(-1) and 1.25 L mmol(-1) for Zn(II) and Cd(II), respectively. In two
      component systems, Zn(II) and Cd(II) adsorption capacities were reduced by 50%
      and 40%, respectively and the biosorbent showed a preference for Cd(II) over
      Zn(II). HNO(3) (0.1M) and EDTA (0.1M) achieved 90-100% desorption of both ions
      from the loaded biomass. While HNO(3) preserved the biomass structure, EDTA
      destroyed it completely. Fourier transform infrared spectra identified the
      contribution of carboxylic, amine and sulfonate groups on Zn(II) and Cd(II)
      biosorption. These results showed that biosorption using M. pyrifera-treated
      biomass could be an affordable and simple process for cadmium and zinc removal
      from wastewaters.

PMID- 22609677
TI  - Biodegradation of BTEX in a fungal biofilter: influence of operational
      parameters, effect of shock-loads and substrate stratification.
AB  - The effect of relative humidity (RH: 30% to >95%) of a gas-phase mixture composed
      of benzene, toluene, ethylbenzene and para-, meta- and ortho-xylenes (BTEX),
      inlet concentrations (0.2-12.6 g m(-3)), and empty bed residence times (EBRTs)
      (48-144 s) was tested in a fungi-dominant biofilter. A maximum elimination
      capacity (EC(max)) of 244.2 gBTEX m(-3) h(-1) was achieved at a total inlet
      loading rate (ILR(T)) of 371.2 gBTEXm(-3) h(-1) (RH: 65%). The transient-state
      response was tested by increasing the ILR(T), in two steps, from ~50 to 850 gm(
      3) h(-1) and from ~50 to 320 g m(-3) h(-1), at a constant EBRT of 41.7s.
      Increasing the ILR(T) reduced the total BTEX removal efficiency (RE(T)) from >97%
      to 35%, and from >90% to 60% during medium and high shock-load, respectively.
      When subjected to short (4d) and long-term (7d) shut-down periods, the biofilter
      was able to recover high EC(max) of, respectively, 200 and 72 gBTEX m(-)3 h(-1)
      after resuming operation.

PMID- 22609678
TI  - Vermicomposting of milk processing industry sludge spiked with plant wastes.
AB  - This work illustrates the vermistabilization of wastewater sludge from a milk
      processing industry (MPIS) unit spiked with cow dung (CD), sugarcane trash (ST)
      and wheat straw (WS) employing earthworms Eisenia fetida. A total of nine
      experimental vermibeds were established and changes in chemical parameters of
      waste material have been observed for 90 days. Vermistabilization caused
      significant reduction in pH, organic carbon and C:N ratio and substantial
      increase in total N, available P and exchangeable K. The waste mixture containing
      MPIS (60%)+CD (10%)+ST (30%) and MPIS (60%)+CD (10%)+WS (30%) had better waste
      mineralization rate among waste mixtures studied. The earthworm showed better
      biomass and cocoon numbers in all vermibeds during vermicomposting operation.
      Results, thus suggest the suitability of E. fetida for conversion of noxious
      industrial waste into value-added product for land restoration programme.

PMID- 22609679
TI  - Hydrolysis of sweet sorghum bagasse and eucalyptus wood chips with liquid hot
      water.
AB  - The chemical composition, hydrolysis products, and kinetics during liquid hot
      water pretreatment of sweet sorghum bagasse (SSB) and eucalyptus wood chips (EWC)
      were investigated. Under optimal conditions, a total xylose recovery of 79.6% and
      55.6% for SSB and of 74.9% and 84.4% for EWC was achieved after pretreatments in
      a step-change flow rate reactor (184  degrees C, 20 ml/min, 8 min, and 10 ml/min,
      10 min) and batch stirred reactor (184  degrees C, 5%w/v, 18 min), respectively.
      More than 90% of the xylose was recovered as oligomers from SSB, independent of
      the type of reactor employed. The activation energies of xylan decomposition of
      SSB in the step-change flow rate reactor was 6.5-fold greater than that of EWC in
      the batch stirred reactor due to accumulation of acidic products. These findings
      show that sugar recovery is dependent on the reactor configuration for specific
      substrates.

PMID- 22609680
TI  - Halogenated flame retardants in home-produced eggs from an electronic waste
      recycling region in South China: levels, composition profiles, and human dietary
      exposure assessment.
AB  - Three regulated halogenated flame retardants (HFRs), i.e., polybrominated
      diphenyl ethers (PBDEs), polybrominated biphenyls (PBBs) and
      hexabromocyclododecanes (HBCDs), and several alternative HFRs (AHFRs) including
      Dechlorane Plus (DP), decabromodiphenyl ethane (DBDPE), and 1,2-bis(2,4,6
      tribromophenoxy) ethane (BTBPE), were investigated in the home-produced eggs from
      three recycling sites and a reference site in an electronic waste (e-waste)
      recycling region, South China. Mean levels of HFRs in eggs from the recycling
      sites ranged 2640-14100, 700-1620, 44-350, and 720-3920 ng/g lipid weight for
      ?PBDEs, ?PBBs, ?HBCDs, and ?AHFRs, respectively, which were one to two orders of
      magnitude higher than those examined in the reference site. PBDEs were the
      predominant HFR in those eggs, with contributions >50% to the total HFRs;
      followed by PBBs and the AHFRs (contributing 14-22% in average). The alpha-HBCD
      was the predominant diastereoisomers of HBCDs, with preferential enrichment of
      the (-)-enantiomer in most of the eggs; but no significant stereoselective
      enrichment of the DP isomers was observed in these eggs. The average estimated
      daily intakes (EDIs) of PBDEs, PBBs, HBCDs, and the AHFRs via eggs from the
      recycling sites ranged 4200-20000, 1120-2440, 80-490, and 970-4530 ng/day,
      respectively, which were one to two orders of magnitude higher than those
      reported from other parts of the world. The potential adverse effects of these
      HFRs to human health in the e-waste sites should be further investigated. This is
      the first report on the isomer compositions of DP and the chiral signatures of
      HBCDs in hen eggs.

PMID- 22609681
TI  - Preparation of biocompatible chitosan grafted poly(lactic acid) nanoparticles.
AB  - Chitosan grafted poly(lactic acid) (CS-g-PLA) copolymer was synthesized and
      characterized by FT-IR and elemental analysis. The degree of poly(lactic acid)
      substitution on chitosan was 1.90 +/- 0.04%. The critical aggregation
      concentration of CS-g-PLA in distilled water was 0.17 mg/ml. Three methods of
      preparing CS-g-PLA nanoparticles (diafiltration method, ultrasonication method
      and diafiltration combined with ultrasonication method) were investigated and
      their effect was compared. Of the three methods, diafiltration combined with
      ultrasonication method produced nanoparticles with optimal property in terms of
      size and morphology, with size ranging from 133 to 352 nm and zeta potential from
      36 to 43 mV. Also, the hemolytic activity and cytotoxicity of the CS-g-PLA based
      nanoparticles was tested, and results showed low hemolysis rate (<5%) and no
      significant cytotoxicity effect of these nanoparticles.

PMID- 22609682
TI  - Characterization of diadzein-hemoglobin binding using optical spectroscopy and
      molecular dynamics simulations.
AB  - The present study establishes the effectiveness of natural drug delivery
      mechanisms and investigates the interactions between drug and its natural
      carrier. The binding between the isoflavone diadzein (DZN) and the natural
      carrier hemoglobin (HbA) was studied using optical spectroscopy and molecular
      dynamics simulations. The inherent fluorescence emission characteristics of DZN
      along with that of tryptophan (Trp) residues of the protein HbA were exploited to
      elucidate the binding location and other relevant parameters of the drug inside
      its delivery vehicle HbA. Stern-Volmer studies at different temperatures indicate
      that static along with collisional quenching mechanisms are responsible for the
      quenching of protein fluorescence by the drug. Molecular dynamics and docking
      studies supported the hydrophobic interactions between ligand and protein, as was
      observed from spectroscopy. DZN binds between the subunits of HbA, ~15 A away
      from the closest heme group of chain alpha1, emphasizing the fact that the drug
      does not interfere with oxygen binding site of HbA.

PMID- 22609683
TI  - Macromolecular complexes of BSA with gelatin.
AB  - This work studies the effect of the helix-coil transition in gelatin on the
      structure development in the complex forming water-gelatin-BSA system using
      dynamic light scattering, environment scanning electron microscopy, rheometry,
      differential scanning microcalorimetry, circular dichroism, fluorescence, and
      absorption measurements. It was established that the structure of the complexes
      formed and the mechanism of intermacromolecular interaction are different in the
      case of two conformation states of gelatin. Above the temperature of the
      conformational transition (40  degrees C) intermacromolecular interaction leads
      to collapse gelatin macromolecules and formation compact (30 nm in radius) BSA
      gelatin complexes (~6:1, mole/mole), partial stabilization of the secondary
      structure (increase the mean helix content), and stabilization of BSA molecules
      against thermo aggregation. At the same time it does not leads to an appreciable
      change in the thermodynamic parameters of the thermal transitions for BSA and
      gelatin. Below the temperature of the conformation transition (at 18  degrees C)
      the interaction results in formation of the large (600-1000 nm in radius) complex
      particles due to trapping BSA molecules into the meshes of the gelatin network
      and, as consequence, a substantial increase in the storage and loss moduli of the
      system.

PMID- 22609684
TI  - Benzophenone glycosides and epicatechin derivatives from Malania oleifera.
AB  - A new benzophenone C-glycoside, malaferin A (1), and two new epicatechin
      derivatives, malaferin B (2) and malaferin C (3), together with five known
      compounds were isolated from Malania oleifera. In addition, (-)-epicatechin-3-O
      benzoate (6) was isolated for the first time from a natural resource. Structures
      of 1-3 were determined on the basis of their spectroscopic methods, including 1D
      and 2D NMR techniques. All of the compounds were evaluated for anti-HIV
      activities.

PMID- 22609685
TI  - Norditerpenoids from Salvia castanea Diels f. pubescens.
AB  - Three new norditerpenoids, castanol A-C (1-3), along with eighteen known
      diterpenoids, were isolated from Salvia castanea Diels f. pubescens. Their
      structures were elucidated by extensive spectroscopic analysis. All compounds
      were evaluated for their cytotoxic activities against five human cancer cell
      lines. The known compounds neo-tanshinlactone (12) and methyltanshinoate (17)
      exhibited significant cytotoxic activities against some cells.

PMID- 22609686
TI  - Thermodynamic constraints shape the structure of carbon fixation pathways.
AB  - Thermodynamics impose a major constraint on the structure of metabolic pathways.
      Here, we use carbon fixation pathways to demonstrate how thermodynamics shape the
      structure of pathways and determine the cellular resources they consume. We
      analyze the energetic profile of prototypical reactions and show that each
      reaction type displays a characteristic change in Gibbs energy. Specifically,
      although carbon fixation pathways display a considerable structural variability,
      they are all energetically constrained by two types of reactions: carboxylation
      and carboxyl reduction. In fact, all adenosine triphosphate (ATP) molecules
      consumed by carbon fixation pathways - with a single exception - are used,
      directly or indirectly, to power one of these unfavorable reactions. When an
      indirect coupling is employed, the energy released by ATP hydrolysis is used to
      establish another chemical bond with high energy of hydrolysis, e.g. a thioester.
      This bond is cleaved by a downstream enzyme to energize an unfavorable reaction.
      Notably, many pathways exhibit reduced ATP requirement as they couple unfavorable
      carboxylation or carboxyl reduction reactions to exergonic reactions other than
      ATP hydrolysis. In the most extreme example, the reductive acetyl coenzyme A
      (acetyl-CoA) pathway bypasses almost all ATP-consuming reactions. On the other
      hand, the reductive pentose phosphate pathway appears to be the least ATP
      efficient because it is the only carbon fixation pathway that invests ATP in
      metabolic aims other than carboxylation and carboxyl reduction. Altogether, our
      analysis indicates that basic thermodynamic considerations accurately predict the
      resource investment required to support a metabolic pathway and further
      identifies biochemical mechanisms that can decrease this requirement.

PMID- 22609687
TI  - Hydration-layer models for cryo-EM image simulation.
AB  - To compare cryo-EM images and 3D reconstructions with atomic structures in a
      quantitative way it is essential to model the electron scattering by solvent
      (water or ice) that surrounds protein assemblies. The most rigorous method for
      determining the density of solvating water atoms for this purpose has been to
      perform molecular-dynamics (MD) simulations of the protein-water system. In this
      paper we adapt the ideas of bulk-water modeling that are used in the refinement
      of X-ray crystal structures to the cryo-EM solvent-modeling problem. We present a
      continuum model for solvent density which matches MD-based results to within
      sampling errors. However, we also find that the simple binary-mask model of Jiang
      and Brunger (1994) performs nearly as well as the new model. We conclude that
      several methods are now available for rapid and accurate modeling of cryo-EM
      images and maps of solvated proteins.

PMID- 22609688
TI  - Synthesis, characterisation and theoretical study of ruthenium 4,4'-bi-1,2,3
      triazolyl complexes: fundamental switching of the nature of S1 and T1 states from
      MLCT to MC.
AB  - The series of complexes [Ru(bpy)(3-n)(btz)(n)][PF(6)](2) (bpy = 2,2'-bipyridyl,
      btz = 1,1'-dibenzyl-4,4'-bi-1,2,3-triazolyl, 2n = 1, 3n = 2, 4n = 3) have been
      prepared and characterised, and the photophysical and electronic effects imparted
      by the btz ligand were investigated. Complexes 2 and 3 exhibit MLCT absorption
      bands at 425 and 446 nm respectively showing a progressive blue-shift in the
      absorption on increasing the btz ligand content when compared to
      [Ru(bpy)(3)][Cl](2) (1). Complex 4 exhibits a heavily blue-shifted absorption
      spectrum with respect to those of 1-3, indicating that the LUMO of the latter are
      bpy-centred with little or no btz contribution whereas that of 4 is necessarily
      btz-centred. DFT calculations on analogous complexes 1'-4' (in which the benzyl
      substituents are replaced by methyl) show that the HOMO-LUMO gap increases by 0.3
      eV from 1'-3' through destabilisation of the LUMO with respect to the HOMO. The
      HOMO-LUMO gap of 4' increases by 0.98 eV compared to that of 3' due to
      significant destabilisation of the LUMO. Examination of TDDFT data show that the
      S(1) states of 1'-3' are (1)MLCT in character whereas that of 4' is (1)MC. The
      optimisation of the T(1) state of 4' leads to the elongation of two mutually
      trans Ru-N bonds to yield [Ru(kappa(2)-btz)(kappa(1)-btz)(2)](2+), confirming the
      (3)MC character. Thus, replacement of bpy by btz leads to a fundamental change in
      the ordering of excited states such that the nature of the lowest energy excited
      state changes from MLCT in nature to MC.

PMID- 22609689
TI  - Optical self-energy in graphene due to correlations.
AB  - In highly correlated systems one can define an optical self-energy in analogy to
      its quasiparticle (QP) self-energy counterpart. This quantity provides useful
      information on the nature of the excitations involved in inelastic scattering
      processes. Here we calculate the self-energy of the intraband optical transitions
      in graphene originating in the electron-electron interaction (EEI) as well as
      electron-phonon interaction (EPI). Although optics involves an average over all
      momenta (k) of the charge carriers, the structure in the optical self-energy is
      nevertheless found to mirror mainly that of the corresponding quasiparticles for
      k equal to or near the Fermi momentum k(F). Consequently, plasmaronic structures
      which are associated with momenta near the Dirac point at k = 0 are not important
      in the intraband optical response. While the structure of the electron-phonon
      interaction (EPI) reflects the sharp peaks of the phonon density of states, the
      excitation spectrum associated with the electron-electron interaction is in
      comparison structureless and flat and extends over an energy range which scales
      linearly with the value of the chemical potential. We introduce a method whereby
      detailed quantitative information on such excitation spectra can be extracted
      from optical data. Modulations seen on the edge of the interband optical
      conductivity as it rises towards its universal background value are traced to
      structure in the quasiparticle self-energies around k(F) of the lower Dirac cone
      associated with the occupied states.

PMID- 22609690
TI  - Persistence of engineered nanoparticles in a municipal solid-waste incineration
      plant.
AB  - More than 100 million tonnes of municipal solid waste are incinerated worldwide
      every year. However, little is known about the fate of nanomaterials during
      incineration, even though the presence of engineered nanoparticles in waste is
      expected to grow. Here, we show that cerium oxide nanoparticles introduced into a
      full-scale waste incineration plant bind loosely to solid residues from the
      combustion process and can be efficiently removed from flue gas using current
      filter technology. The nanoparticles were introduced either directly onto the
      waste before incineration or into the gas stream exiting the furnace of an
      incinerator that processes 200,000 tonnes of waste per year. Nanoparticles that
      attached to the surface of the solid residues did not become a fixed part of the
      residues and did not demonstrate any physical or chemical changes. Our
      observations show that although it is possible to incinerate waste without
      releasing nanoparticles into the atmosphere, the residues to which they bind
      eventually end up in landfills or recovered raw materials, confirming that there
      is a clear environmental need to develop degradable nanoparticles.

PMID- 22609691
TI  - A pilot study in non-human primates shows no adverse response to intravenous
      injection of quantum dots.
AB  - Quantum dots have been used in biomedical research for imaging, diagnostics and
      sensing purposes. However, concerns over the cytotoxicity of their heavy metal
      constituents and conflicting results from in vitro and small animal toxicity
      studies have limited their translation towards clinical applications. Here, we
      show in a pilot study that rhesus macaques injected with phospholipid micelle
      encapsulated CdSe/CdS/ZnS quantum dots do not exhibit evidence of toxicity. Blood
      and biochemical markers remained within normal ranges following treatment, and
      histology of major organs after 90 days showed no abnormalities. Our results show
      that acute toxicity of these quantum dots in vivo can be minimal. However,
      chemical analysis revealed that most of the initial dose of cadmium remained in
      the liver, spleen and kidneys after 90 days. This means that the breakdown and
      clearance of quantum dots is quite slow, suggesting that longer-term studies will
      be required to determine the ultimate fate of these heavy metals and the impact
      of their persistence in primates.

PMID- 22609693
TI  - Composite materials. Taking a leaf from nature's book.
AB  - Amyloid protein fibrils and graphene sheets can be combined to make a material
      that is biodegradable and has useful shape-memory and enzyme-sensing properties.

PMID- 22609694
TI  - KCC3-dependent chloride extrusion in adult sensory neurons.
AB  - The cation-Cl(-) cotransporters participate to neuronal Cl(-) balance and are
      responsible for the post-natal Cl(-) switch in central neurons. In the adult
      peripheral nervous system, it is not well established whether a Cl(-) transition
      occurs during maturation. We investigated the contribution of cation-Cl(-)
      cotransporters in the Cl(-) handling of sensory neurons derived from the dorsal
      root ganglia (DRG) of neonatal mice (postnatal days 1-6) and adult mice.
      Gramicidin-perforated patch-clamp recordings in wild-type neurons revealed that
      Cl(-) accumulated to very high values in P1-6 sensory neurons and decreased in
      adulthood. In post-natal sensory neurons, quantitative RT-PCR showed that NKCC1,
      KCC1 and KCC3 had a higher transcript expression level compared to KCC2 and KCC4.
      NKCC1 was the main cation-Cl(-) cotransporter controlling Cl(-) accumulation at
      this developmental stage. In adulthood, the KCC3 transcript was produced in
      larger amounts than the other cation-Cl(-) cotransporter transcripts and RT-PCR
      shows larger expression of the shorter KCC3a isoform in adult DRG.
      Pharmacological inhibitors of cation-Cl(-) cotransporters and the use of KCC3(-/
      ) mice demonstrated that NKCC1 sustained Cl(-) accumulation in the majority of
      adult sensory neurons while KCC3 contributed to Cl(-) extrusion in a subset of
      these neurons. Beta-galactosidase detection in adult KCC3(-/-) DRG showed that
      KCC3 transcripts were present in all adult sensory neurons suggesting a KCC3
      isoform specific regulation of Cl(-) handling. The contribution of KCC3 to Cl(-)
      extrusion in a subset of sensory neurons indicates that KCC3 could play a major
      role in GABAergic/glycinergic transmission.

PMID- 22609696
TI  - Managing patient deterioration: assessing teamwork and individual performance.
AB  - OBJECTIVE: To assess the ability of rural Australian nurse teams to manage
      deteriorating patients. METHODS: This quasi-experimental design used pre- and
      post-intervention assessments and observation to evaluate nurses' simulated
      clinical performance. Registered nurses (n=44) from two hospital wards completed
      a formative knowledge assessment and three team-based video recorded scenarios
      (Objective Structured Clinical Examinations (OSCE)). Trained patient actors
      simulated deteriorating patients. Skill performance and situation awareness were
      measured and team performance was rated using the Team Emergency Assessment
      Measure. RESULTS: Knowledge in relation to patient deterioration management
      varied (mean 63%, range 27-100%) with a median score of 64%. Younger nurses with
      a greater number of working hours scored the highest (p=0.001). OSCE performance
      was generally low with a mean performance of 54%, but performance was maintained
      despite the increasing complexity of the scenarios. Situation awareness was
      generally low (median 50%, mean 47%, range 17-83%, SD 14.03) with significantly
      higher levels in younger participants (r=-0.346, p=0.021). Teamwork ratings
      averaged 57% with significant associations between the subscales (Leadership,
      Teamwork and Task Management) (p<0.006), the global rating scale (p<0.001) and
      two of the OSCE measures (p<0.049). Feedback from participants following the
      programme indicated significant improvements in knowledge, confidence and
      competence (p<0.001). CONCLUSION: Despite a satisfactory knowledge base, the
      application of knowledge was low with notable performance deficits in these
      demanding and stressful situations. The identification and management of patient
      deterioration needs to be taught in professional development programmes
      incorporating high fidelity simulation techniques. The Team Emergency assessment
      tool proved to be a valid measure of team performance in patient deterioration
      scenarios.

PMID- 22609697
TI  - The use of recombinant activated factor VII (rFVIIa) in the management of
      patients with major haemorrhage in military hospitals over the last 5 years.
AB  - INTRODUCTION: Recombinant activated factor VII (rFVIIa) has been used in the
      management of traumatic haemorrhage for a decade. Anecdotally, its use is
      decreasing. The aim of this study was to define the use of rFVIIa in UK deployed
      military hospitals over the last 5 years. METHODS: A retrospective database
      review was performed, using the Joint Theatre Trauma Registry, for the period
      January 2006 to June 2011. Data collected included use of rFVIIa, injury severity
      score (ISS), survival and injury pattern. The temporal trend of rFVIIa use,
      taking into account the number of severely injured patients presenting during
      each time period, was then analysed. RESULTS: During the period January 2006 to
      June 2011, 156 injured patients received rFVIIa. 146 of these (94%) had an ISS
      >15; there were 45 fatalities. The median ISS among the group receiving rFVIIa
      was 30, and 20 patients had an ISS in the range 60-75. There was a significant
      reduction in the use of rFVIIa in the second half of 2010 and the first half of
      2011, compared with the previous 12-month period. CONCLUSION: The use of rFVIIa
      in UK deployed military hospitals has declined since 2010, which is likely due to
      a combination of factors, including a change in resuscitation practice in these
      units, and a change in emphasis of manufacturer's guidance.

PMID- 22609695
TI  - Developmental lead effects on behavior and brain gene expression in male and
      female BALB/cAnNTac mice.
AB  - Lead (Pb) was one of the first poisons identified, and the developing nervous
      system is particularly vulnerable to its toxic effects. Relatively low,
      subclinical doses, of Pb that produce no overt signs of encephalopathy can affect
      cognitive, emotional, and motor functions. In the present study, the effects of
      developmental Pb-exposure on behavioral performance and gene expression in
      BALB/cAnNTac mice were evaluated. Pups were exposed to Pb from gestational-day
      (gd) 8 to postnatal-day (pnd) 21 and later evaluated in exploratory behavior,
      rotarod, Morris water maze, and resident-intruder assays as adults. Pb-exposure
      caused significant alterations in exploratory behavior and water maze performance
      during the probe trial, but rotarod performance was not affected. Pb-exposed
      males displayed violent behavior towards their cage mates, but not to a stranger
      in the resident-intruder assay. Gene expression analysis at pnd21 by microarray
      and qRT-PCR was performed to provide a molecular link to the behavior changes
      that were observed. Pb strongly up-regulated gene expression within the signaling
      pathways of mitogen activated protein kinases (MAPKs), extra-cellular matrix
      (ECM) receptor, focal adhesion, and vascular endothelial growth-factor (VEGF),
      but Pb down-regulated gene expression within the pathways for glycan structures
      biosynthesis 1, purine metabolism, and N-glycan biosynthesis. Pb increased
      transcription of genes for major histocompatibility (MHC) proteins, the chemokine
      Ccl28, chemokine receptors, IL-7, IL7R, and proteases. The qRT-PCR analysis
      indicated an increase of gene expression in the whole brain for caspase 1 and
      NOS2. Analysis of IL-1beta, caspase 1, NOS2, Trail, IL-18 and IL-33 gene
      expression of brain regions indicated that Pb perturbed the inter-regional
      expression pattern of pro-inflammatory genes. Brain region protein concentrations
      for IL-10, an anti-inflammatory cytokine, showed a significant decrease only
      within the cortex region. Results indicate that Pb differentially affects the
      behavior of male and female mice in that females did less exploration and the
      males were selectively more aggressive. Gene expression data pointed to evidence
      of neuroinflammation in the brain of both female and male mice. Pb had more of an
      effect in the males on expression of vomeronasal receptor genes associated with
      odor detection and social behavior.

PMID- 22609698
TI  - Adrenal trauma: medical and surgical emergency.
AB  - A 35-year-old man was admitted to hospital in a state of haemorrhagic shock after
      a road traffic accident. A right adrenal gland injury associated with a
      retroperitoneal haematoma was diagnosed by CT scan. Haemostatic surgery (without
      adrenal gland resection) was performed instead of angioembolisation because of an
      associated abdominal compartment syndrome. The outcome was favourable. The
      objective of this case report is to illustrate the importance of the early
      diagnosis of adrenal gland injuries after trauma which, though uncommon and
      frequently overlooked or discovered fortuitously by CT scan, can be life
      threatening. Angioembolisation or surgery may be necessary in cases of
      uncontrolled bleeding or the development of abdominal compartmental syndrome.

PMID- 22609700
TI  - The neurobiology of depression in later-life: clinical, neuropsychological,
      neuroimaging and pathophysiological features.
AB  - As the population ages, the economic and societal impacts of neurodegenerative
      and neuropsychiatric disorders are expected to rise sharply. Like dementia, late
      life depressive disorders are common and are linked to increased disability, high
      healthcare utilisation, cognitive decline and premature mortality. Considerable
      heterogeneity in the clinical presentation of major depression across the life
      cycle may reflect unique pathophysiological pathways to illness; differentiating
      those with earlier onset who have grown older (early-onset depression), from
      those with illness onset after the age of 50 or 60 years (late-onset depression).
      The last two decades have witnessed significant advances in our understanding of
      the neurobiology of early- and late-onset depression, and has shown that
      disturbances of fronto-subcortical functioning are implicated. New biomedical
      models extend well beyond perturbations of traditional monoamine systems to
      include altered neurotrophins, endocrinologic and immunologic system dysfunction,
      inflammatory processes and gene expression alterations. This more recent research
      has highlighted that a range of illness-specific, neurodegenerative and vascular
      factors appear to contribute to the various phenotypic presentations. This review
      highlights the major features of late-life depression, with specific reference to
      its associated aetiological, clinical, cognitive, neuroimaging,
      neuropathological, inflammatory and genetic correlates. Data examining the
      efficacy of pharmacological, non-pharmacological and novel treatments for
      depression are discussed. Ultimately, future research must aim to evaluate
      whether basic biomedical knowledge can be successfully translated into enhanced
      health outcomes via the implementation of early intervention paradigms.

PMID- 22609699
TI  - The outgrowth of micrometastases is enabled by the formation of filopodium-like
      protrusions.
AB  - Disseminated cancer cells that have extravasated into the tissue parenchyma must
      interact productively with its extracellular matrix components to survive,
      proliferate, and form macroscopic metastases. The biochemical and cell biologic
      mechanisms enabling this interaction remain poorly understood. We find that the
      formation of elongated integrin beta(1)-containing adhesion plaques by cancer
      cells that have extravasated into the lung parenchyma enables the proliferation
      of these cells via activation of focal adhesion kinase. These plaques originate
      in and appear only after the formation of filopodium-like protrusions (FLP) that
      harbor integrin beta(1) along their shafts. The cytoskeleton-regulating proteins
      Rif and mDia2 contribute critically to the formation of these protrusions and
      thereby enable the proliferation of extravasated cancer cells. Hence, the
      formation of FLPs represents a critical rate-limiting step for the subsequent
      development of macroscopic metastases. SIGNIFICANCE: Although the mechanisms of
      metastatic dissemination have begun to be uncovered, those involved in the
      establishment of extravasated cancer cells in foreign tissue microenvironments
      remained largely obscure. We have studied the behavior of recently extravasated
      cancer cells in the lungs and identified a series of cell biologic processes
      involving the formation of filopodium-like protrusions and the subsequent
      development of elongated, mature adhesion plaques, which contribute critically to
      the rapid proliferation of the micrometastatic cells and thus are prerequisites
      to the eventual lung colonization by these cells.

PMID- 22609701
TI  - Lymph node metastasis from colon carcinoma at 11 years after the initial
      operation managed by lymph node resection and chemoradiation: A case report and a
      review of the literature.
AB  - INTRODUCTION: Lymph node metastasis from colorectal cancer after a disease-free
      interval (DFI) of >5years is extremely rare, and occurs in <0.6% cases.
      PRESENTATION OF CASE: A 60-year-old man underwent low anterior resection for
      sigmoid colon cancer. The lesion was an adenocarcinoma with no lymph node
      metastasis of Stage II. At 9years after the colectomy, he was diagnosed with
      prostate cancer and was treated with radiation and hormonal therapies; at
      11years, he exhibited suddenly elevated carcinoembryonic antigen levels. Computed
      tomography (CT) and positron emission tomography-CT revealed a 2.0-cm para-aortic
      lymph nodes swelling invading the small intestine. These lymph nodes and the
      affected segment of the small intestine were resected, and histopathology of the
      resected specimen confirmed a metastatic tumor. The patient was administered
      radiation therapy after 22 cycles of 5-fluorouracil, oxaliplatin and leucovorin.
      He however presented with a residual lesion in the para-aortic lymph node, but
      currently, he has been symptom free for 4years. DISCUSSION: A review of the
      literature indicates that the median survival of all previously reported patients
      is 12months, and that colon cancer with a long DFI might be a slow growing. One
      of these patients and our patient both had received radiation and/or hormonal
      therapy for another cancer, which probably impaired their immune systems, thus
      resulting in metastatic tumors. CONCLUSION: We report a case of lymph node
      metastasis after a DFI of >5years and review relevant literature to assess the
      significance and possible reasons for delayed colorectal cancer metastases.

PMID- 22609702
TI  - Giant pancreatic incidentaloma: Report of a case and literature review.
AB  - INTRODUCTION: Asymptomatic lesions of the pancreas, referred to as
      'incidentalomas', have appeared with increased frequency in recent years. Giant
      incidentalomas have rarely been reported in the literature. PRESENTATION OF CASE:
      We report herein a rare case of a giant cystic pancreatic incidentaloma measuring
      12.7cm*8cm, which was found in an otherwise healthy male patient during a routine
      genitourinary imaging work-up. The patient underwent a distal pancreatectomy and
      splenectomy; the pathology report demonstrated a giant serous cystadenoma of the
      body and tail of the pancreas. DISCUSSION: The management of pancreatic
      incidentalomas is challenging. While solid lesions almost always warrant surgery,
      there is ongoing debate concerning the management of cystic lesions that are
      found incidentally in the pancreas and have no clinical manifestations.
      CONCLUSION: We report herein an interesting case of a voluminous incidental
      cystic pancreatic lesion. The appropriate approach and the decision whether to
      operate or not in such cases can be puzzling to the physician.

PMID- 22609703
TI  - A safe treatment option for esophageal bezoars.
AB  - INTRODUCTION: Bezoar in the esophagus is a rare condition and associated with
      structural or functional abnormalities of the esophagus. Endoscopy is the main
      tool for diagnosis and treatment for bezoar in the esophagus. PRESENTATION OF
      CASE: Here we present a case where an endoscopic evacuation of an esophageal
      bezoar was unsuccessful. We treated the bezoar through a nasogastric tube using a
      cocktail composed of pancreatic enzymes dissolved in Coca-Cola. DISCUSSION:
      Endoscopy is regarded as the mainstay for the diagnosis and treatment of
      esophageal bezoars. However, when this approach fails, other treatment options
      include dissolution therapy, and surgical exploration and removal of the bezoar.
      Surgical removal of an esophageal bezoar is associated with a high risk of
      morbidity and mortality. We advocate that dissolving therapy should be the first
      choice of treatment when endoscopic evacuation is not possible. CONCLUSION: This
      is the first report describing a successful treatment of an esophageal bezoar
      with a cocktail of Coca-Cola and pancreatic enzymes. It is an effective,
      inexpensive, and worldwide available treatment and should be considered when
      endoscopic evacuation fails.

PMID- 22609704
TI  - Colonic lymphoma presenting acutely with perforated colo-splenic fistula.
AB  - INTRODUCTION: Primary colonic lymphoma is rare. It comprises less than 1% of
      large bowel malignancies. Affected patients often present with non-specific vague
      symptoms with subsequent delays in diagnosis and management. PRESENTATION OF
      CASE: An immuno-competent 35-year-old male presented with left iliac fossa pain,
      fever and constipation. Clinical examination revealed left-sided abdominal
      peritonism. After the initial radiological and endoscopic investigations, a
      provisional diagnosis of a localized perforation of a splenic flexure
      diverticulum was made and ultrasound-guided percutaneous drainage of the abscess
      was performed. The patient failed to settle on conservative treatment and
      therefore exploratory laparotomy was carried out. An inflammatory phlegmon
      consisting of a left paracolic gutter abscess, the spleen and the splenic flexure
      of the colon was resected en-bloc and a primary colo-colic anastomosis was
      performed. His operative recovery was complicated by wound infection which was
      treated conservatively. The histopathology revealed colo-splenic fistula
      secondary to a perforated colonic non-Hodgkin's lymphoma. The spleen contained
      multiple metastatic lymphomatous deposits. He was started on chemotherapy and
      remained well at 5-year follow up. DISCUSSION: Colon non-Hodgkin's lymphoma may
      present initially with an acute abdomen due to perforation. It mimics any acute
      surgical condition. Perforation and fistulaization into the spleen is very rare.
      CONCLUSION: This case highlights the delay and difficulty in diagnosing primary
      colonic lymphoma without resorting to surgical resection.

PMID- 22609705
TI  - Multimodality treatment of a complex series of parallel pathologies in a 16-year
      old male that ultimately leads to bilateral hip arthroplasty surgery: A case
      report.
AB  - INTRODUCTION: Femoral head osteonecrosis is associated with significant sequelae
      for the patient in the long-term. A combination of factors are thought to
      contribute to the pathophysiology behind this debilitating disease process.
      PRESENTATION OF CASE: We report on a 16-year-old adolescent male requiring staged
      bilateral hybrid hip arthroplasty within 3years of diagnosis of acute
      lymphoblastic leukaemia that ran a complicated course of multimodality treatment.
      DISCUSSION: The case examines the literature on femoral head osteonecrosis in
      this population cohort and the challenge for the orthopaedic surgeon in the
      management of this increasingly prevalent condition. CONCLUSION: In a young
      population cohort, it is important to have arthroplasty surgery as part of the
      management armamentarium, especially when coupled with complex pathology.

PMID- 22609706
TI  - Lipid production of Chlorella vulgaris from lipid-extracted microalgal biomass
      residues through two-step enzymatic hydrolysis.
AB  - Lipid-extracted microalgal biomass residues (LMBRs) were treated using cellulase,
      neutrase and alcalase in a two-step process and the resulting hydrolysates were
      used as a source of nutrients for the cultivation of Chlorella vulgaris under non
      aerated and aerated conditions for lipid production. Aeration was favorable for
      cell growth and lipid accumulation and a biomass of approximately 3.28 g L(-1),
      lipid content of 35% and lipid productivity of 116 mg L(-1) d(-1) were obtained.
      Thus, the tested mode of LMBRs utilization was effective for nutrient recycling
      in microalgal biodiesel production.

PMID- 22609707
TI  - Pseudo-lignin formation and its impact on enzymatic hydrolysis.
AB  - Pseudo-lignin, which can be broadly defined as aromatic material that yields a
      positive Klason lignin value and is not derived from native lignin, has been
      recently reported to form during the dilute acid pretreatment of poplar
      holocellulose. To investigate the chemistry of pseudo-lignin formation, GPC, FT
      IR and 13C NMR were utilized to characterize pseudo-lignin extracted from dilute
      acid pretreated alpha-cellulose and holocellulose. The results showed that pseudo
      lignin consisting of carbonyl, carboxylic, aromatic and aliphatic structures was
      produced from dilute acid pretreated cellulose and hemicellulose. Pseudo-lignin
      extracted from holocellulose pretreated at different conditions had similar
      molecular weights (Mn~1000 g/mol; Mw~5000 g/mol) and structural features
      (carbonyl, carboxylic, aromatic and methoxy structures). These characterizations
      have provided the pseudo-lignin formation mechanisms during pretreatment. The
      presence and structure of pseudo-lignin is important since pseudo-lignin
      decreases the enzymatic conversion.

PMID- 22609708
TI  - Moisture variation associated with water input and evaporation during sewage
      sludge bio-drying.
AB  - The variation of moisture during sewage sludge bio-drying was investigated. In
      situ measurements were conducted to monitor the bulk moisture and water vapor,
      while the moisture content, water generation, water evaporation and aeration
      water input of the bio-drying bulk were calculated based on the water mass
      balance. The moisture in the sewage sludge bio-drying material decreased from 66%
      to 54% in response to control technology for bio-drying. During the temperature
      increasing and thermophilic phases of sewage sludge bio-drying, the moisture
      content, water generation and water evaporation of the bulk initially increased
      and then decreased. The peak water generation and evaporation occurred during the
      thermophilic phase. During the bio-drying, water evaporation was much greater
      than water generation, and aeration facilitated the water evaporation.

PMID- 22609709
TI  - Co-fermentation of cellobiose and xylose by Lipomyces starkeyi for lipid
      production.
AB  - Hydrolysates of lignocellulosic biomass contain glucose, xylose, arabinose,
      cellobiose, among other sugars. Effective utilization of these sugars remains
      challenging for microbial conversion, because most microorganisms consume such
      sugars sequentially with a strong preference for glucose. In the present study,
      the oleaginous yeast, Lipomyces starkeyi, was shown to consume cellobiose and
      xylose simultaneously and to produce intracellular lipids from cellobiose, xylose
      and glucose. In flask cultures with glucose, cellobiose or a mixture of
      cellobiose/xylose as carbon sources, overall substrate consumption rates were
      close to 0.6 g/L/h, and lipid coefficients were 0.19 g lipid/g sugar,
      respectively. This cellobiose/xylose co-fermentation strategy provides an
      opportunity to efficiently utilize lignocellulosic biomass for microbial lipid
      production, which is important for biorefinery and biofuel production.

PMID- 22609710
TI  - Fractionating pretreatment of sugarcane bagasse by aqueous formic acid with
      direct recycle of spent liquor to increase cellulose digestibility--the Formiline
      process.
AB  - A lignocellulose pretreatment process was developed with formic acid
      delignification (FAD) followed by alkaline deformylation (AD), which was termed
      as Formiline process. In FAD, more than 80% of lignin and hemicellulose were
      removed, but cellulose formylation also happened. Formic acid concentration (FAC)
      was the most important factor affecting delignification and cellulose
      formylation. Increasing FAC could enhance degree of delignification but also
      increased cellulose formylation. The presence of formyl group could inhibit the
      enzymatic hydrolysis of cellulose; however, removing formyl group with a small
      loading of alkali well recovered cellulose digestibility. The spent liquor could
      be directly recycled for delignification thus significantly decreasing energy
      consumption in solvent recovery. The Formiline-pretreated substrates showed an
      excellent enzymatic digestibility and could be very well converted to ethanol by
      simultaneous saccharafication and fermentation (SSF). The final ethanol
      concentrations were 55.4 and 80.1g/L respectively at initial solid consistencies
      of 15% and 20%.

PMID- 22609711
TI  - Performance and microbial community analysis of a novel bio-cord carrier during
      treatment of a polluted river.
AB  - The performance and microbial community structure of a novel bio-cord carrier
      during treatment of a polluted river at the laboratory scale was investigated.
      The bio-cord exhibited good filtration performance, with 87.2% SS removal and an
      84.9% reduction in turbidity in 120 min, as well as 19.4-34.4%, 55.2-74.0%, 46.2
      55.9% and 13.1-18.5% reductions in the COD, NH3-N, TN and TP, respectively, under
      three different hydraulic retention times. The bio-cord fibers also provided
      suitable conditions and support media for microbial growth. Additionally, 114
      cloned 16S rDNA sequences were composed of Proteobacteria (57.9%), Bacteroidetes
      (17.5%) and other phyla (24.6%). There were great differences in bacterial
      quantity and composition between the surface and inside of the bio-cord.
      Furthermore, nitrifying and denitrifying bacteria were detected, suggesting that
      simultaneous nitrification and denitrification processes were occurring. Overall,
      the results of this study demonstrated that the carrier could attach
      microorganisms for polluted river treatment.

PMID- 22609712
TI  - Adsorption of anionic dyes from aqueous solutions using chemically modified
      straw.
AB  - The effective disposal of redundant straw is a significant work for environmental
      protection and full utilization of resource. In this work, the wheat straw has
      been modified by etherification to prepare a kind of quaternary ammonium straw
      adsorbents. The adsorption behaviors of the modified straw for methyl orange (MO)
      and acid green 25(AG25) were studied in both batch and column systems. The
      adsorption capacity of the straw for both dyes improved evidently after
      modification. The maximal MO and AG25 uptakes were more than 300 and 950 mg g(
      1), respectively. Furthermore, the adsorption equilibrium, kinetics and column
      studies all indicated that the adsorption behavior was a monolayer chemical
      adsorption with an ion-exchange process. In addition, after adsorption of anionic
      dyes, the used adsorbents were successfully applied to adsorb a cationic dye
      directly at suitable conditions in the secondary adsorption. This was due to the
      altered surface structures of the used adsorbents.

PMID- 22609713
TI  - Effects of chemical additives on filtration and rheological characteristics of
      MBR sludge.
AB  - The main goal of this study was to control the fouling phenomena in MBR using
      chemical additives. In the first phase of the study, SMP removal and bound EPS
      formation capacity of chemical additives were determined. Highest SMP removal
      (72%) was achieved by the Poly-2 additive. In the second phase of the study,
      short term filtration tests were conducted. Poly-1 exhibited highest performance
      based on membrane resistance, permeability and average TMP. According to the
      results obtained from constant shear rate tests in fourth phase, no significant
      change in viscosity with time was observed. Studies for the adaptation of
      rheograms to common flow models showed that chitosan and starch was not able to
      fit to Ostwald de Waele and Bingham models. At a shear rate of 73.4 s(-1)
      viscosities of all samples were close to each other. Chitosan and starch achieved
      highest viscosity values at the shear rate of 0.6 s(-1).

PMID- 22609714
TI  - Performance of a continuous flow microbial electrolysis cell (MEC) fed with
      domestic wastewater.
AB  - In this study, MEC performance was investigated in terms of chemical oxygen
      demand (COD) removal, hydrogen production rate and energy consumption during
      continuous domestic wastewater (dWW) treatment at different organic loading rates
      (OLR) and applied voltages (Vapp). While the COD removal efficiency was improved
      at low OLRs, the electrical energy required to remove 1g of COD was significantly
      increased with decreasing the OLR. Hydrogen production exhibited a Monod-type
      trend as function of the OLR reaching a maximum production rate of 0.30 L/(Lrd).
      Optimal Vapp was found to be highly dependent on the strength of the dWW. The
      results also confirmed the fact that MEC performance can be optimized by setting
      Vapp at the onset potential of the diffusion control region. Although low
      columbic efficiencies and the occurrence of hydrogen recycling limited
      significantly the reactor performance, these results demonstrate that MEC can be
      successfully used for dWW treatment.

PMID- 22609715
TI  - Mixing effect on thermophilic anaerobic digestion of source-sorted organic
      fraction of municipal solid waste.
AB  - This paper examines the effect of mixing on the performance of thermophilic
      anaerobic digestion of source-sorted organic fraction of municipal solid waste
      during the start-up phase and in the absence of an acclimated seed. For this
      purpose, two digesters were used under similar starting conditions and operated
      for 235 days with different mixing schemes. While both digesters exhibited a
      successful startup with comparable specific methane yield of 0.327 and 0.314 l
      CH4/g VS, continuous slow stirring improved stability by reducing average VFA
      accumulation from 2890 to 825 mg HAc/l, propionate content from 2073 to 488 mg/l,
      and VFA-to-alkalinity ratio from 0.32 to 0.07. As a result, the startup with slow
      mixing was faster and smoother accomplishing a higher loading capacity of 2.5 g
      VS/l/d in comparison to 1.9 g VS/l/d for non-mixing. Mixing equally improved
      microbial abundance from 6.6 to 10 g VSS/l and enhanced solids and soluble COD
      removal.

PMID- 22609716
TI  - Microbial community structures in different wastewater treatment plants as
      revealed by 454-pyrosequencing analysis.
AB  - In this study, 454-pyrosequencing technology was employed to investigate the
      microbial communities in 12 municipal wastewater treatment plants (WWPTs) with
      different treatment processes. In total, 202,968 effective sequences of the 16S
      rRNA gene were generated from 16 samples that widely represented the diversity of
      the microbial communities. While Proteobacteria was found to be the dominant
      phylum in some samples, in other samples it was Bacteroidetes. The Simpson's
      diversity index and evenness index were lowest in samples from membrane
      bioreactors (MBRs), possibly due to the long sludge retention time (SRT) and low
      food/microorganism ratio (F/M). For one WWTP which had two disparate treatment
      processes operating in parallel, the structures of microbial communities in the
      two systems were compared. The differences found between the two indicated that
      the treatment process likely had effects on the structure of microbial
      communities.

PMID- 22609717
TI  - Nutrient removal from membrane bioreactor permeate using microalgae and in a
      microalgae membrane photoreactor.
AB  - This paper explores the use of a novel microalgae membrane photoreactor (mMR) to
      polish the effluent from an aerobic membrane bioreactor (MBR) fed with domestic
      wastewater. Four microalgae species Chlorella (Chlorella sp.), Chlorella vulgaris
      (C. vulgaris), Scenedesmus quadricauda (S. quadricauda) and Scenedesmus dimorphus
      (S. dimorphus) were isolated from the environment and tested in batch reactors
      fed with permeate from the aerobic MBR to evaluate the nutrient removal rates for
      each species. All four microalgae species were able to completely remove NH4 in
      the reactor within 3 days. The removal rates of NO3, NO2 and PO4 were between 43
      54%, 83-95% and 70-92%, respectively after 3 days in the batch reactor.
      Subsequently, an MBR-mMR system was operated for 23 days. The mMR was able to
      remove on average 50% of NH4, 75% of NO2, 35% of NO3 and 60% of PO4 consistently
      from the MBR effluent under the conditions tested.

PMID- 22609718
TI  - Bactericidal and ammonia removal activity of silver ion-exchanged zeolite.
AB  - The antimicrobial activity of silver-zeolite against Escherichia coli, Vibrio
      harveyi, Vibrio cholerae and Vibrio parahaemolyticus was examined in liquid
      medium and agar well diffusion assays. The minimum inhibitory concentration for
      silver ion-exchanged zeolite against E. coli and V. harveyi was 40 MUg/ml, and 50
      60 MUg/ml for V. cholerae and V. parahaemolyticus. The diameter of the inhibition
      zones for E. coli, V. harveyi, V. cholerae and V. parahaemolyticus, respectively,
      increased from 0.5 to 2.3 cm, 0.6 to 2.4 cm, 0.3 to 1.65 cm and 0.3 to 1.7 cm
      with increasing concentrations of silver ion-exchanged zeolite from 10 to 400
      MUg. Silver-zeolite removed 20-37% ammonia from aqueous solutions. This study
      suggests that silver ion-exchanged zeolite could impact disease and environmental
      management in shrimp aquaculture.

PMID- 22609719
TI  - A viable method and configuration for fermenting biomass sugars to ethanol using
      native Saccharomyces cerevisiae.
AB  - A system that incorporates a packed bed reactor for isomerization of xylose and a
      hollow fiber membrane fermentor (HFMF) for sugar fermentation by yeast was
      developed for facile recovery of the xylose isomerase enzyme pellets and reuse of
      the cartridge loaded with yeast. Fermentation of pre-isomerized poplar
      hydrolysate produced using ionic liquid pretreatment in HFMF resulted in ethanol
      yields equivalent to that of model sugar mixtures of xylose and glucose. By
      recirculating model sugar mixtures containing partially isomerized xylose through
      the packed bed and the HFMF connected in series, 39 g/l ethanol was produced
      within 10h with 86.4% xylose utilization. The modular nature of this
      configuration has the potential for easy scale-up of the simultaneous
      isomerization and fermentation process without significant capital costs.

PMID- 22609720
TI  - Evolution of process parameters and determination of kinetics for co-composting
      of organic fraction of municipal solid waste with poultry manure.
AB  - This study aimed to monitor the process parameters and to determine kinetics in
      composting of organic fraction of municipal solid waste (OFMSW) and poultry
      manure. The experiments were carried out with three different mixtures. The
      results showed that the mixture 60% OFMSW, 20% poultry manure, 10% mature compost
      and 10% sawdust provided the most appropriate conditions for composting process.
      Using nine kinetic models and nonlinear regression method, kinetic parameters
      were estimated and the models were analyzed with four statistical indicators.
      Kinetic models with four measured variables proved to be better than models with
      less number of measured variables. The number of measured experimental variables
      influences kinetics more than the number of kinetic parameters. Satisfactory
      fittings of proposed kinetic model to the experimental data of OM were achieved.
      The model is more suitable for data obtained from composting of mixtures with
      much higher percentage of OFMSW than percentage of poultry manure.

PMID- 22609721
TI  - TCF bleaching sequence in kraft pulping of olive tree pruning residues.
AB  - The aim of the present work was to find a suitable Kraft cooking process for
      olive tree pruning (OTP), in order to produce pulp of kappa number about 17. The
      Kraft pulp produced under optimized conditions showed a viscosity of 31.5 mPa.s
      and good physical, mechanical, and optical properties, which are suitable for
      paper production. The physical-mechanical and optical properties were measured
      before and after bleaching. Although the OTP pulp was bleached to 90.9% ISO
      brightness (kappa<1), the process demanded a long sequence of stages, OZQPOZQPO.
      The bleached pulp showed a brightness reversion equal to 1.3%. Furthermore, this
      bleached pulp did not need a high intensity of beating due to high drainability
      degree in the unbeaten pulp. So that, OTP is suggested as an interesting raw
      material for cellulosic pulp production because its properties are comparable to
      those of other agricultural residues, currently used in the paper industry.

PMID- 22609722
TI  - Courses in stroke and increase in thrombolysis in Andalusia (Spain):  ecological
      fallacy?

PMID- 22609723
TI  - Tracheal intubation during chest compressions performed by qualified emergency
      physicians unfamiliar with the Pentax-Airwayscope.
AB  - OBJECTIVE: Experienced emergency physicians were recruited and a randomized
      crossover trial was conducted to compare the performance of the Pentax
      Airwayscope (AWS) video-laryngoscope with the Macintosh laryngoscope (McL) for
      tracheal intubation during continuous chest compressions under three different
      scenarios: (1) normal airway, (2) limited neck mobility, and (3) tongue edema.
      METHODS: Thirty-six experienced emergency physicians performed intubations on a
      manikin in each of three scenarios. The sequences of scenarios and intubating
      devices were randomized. Time to complete intubation (primary end point), time to
      visualization of the vocal cords, the overall success rate, percentage of glottic
      opening, dental compression, and ease of intubation were determined. RESULTS: The
      times (median [interquartile range]) to complete tracheal intubation were
      significantly shorter with the AWS than the McL in all three scenarios (11.6 [8.0
      14.7] vs. 15.1 [12.8-17.9] s, 13.5 [10.5-20.9] vs. 17.0 [14.1-19.9] s, and 13.6
      [11.1-20.9] vs. 15.1 [18.6-37.5] s, respectively). The overall success rates were
      higher with the AWS than the McL in the difficult intubation scenario (77.8 vs.
      100%). The AWS was also more effective than the McL with respect to the
      percentage of glottic opening, dental compression, and ease of intubation in all
      three scenarios. CONCLUSION: Although participants were experienced emergency
      physicians familiar with the McL and unfamiliar with the AWS, the AWS proved to
      be a better tool than the McL to perform tracheal intubation during continuous
      chest compressions on a manikin. The AWS should be considered as an initial
      intubating tool to perform tracheal intubation during continuous chest
      compressions rather than the McL.

PMID- 22609725
TI  - The role of probabilities in physics.
AB  - Although modern physics was born in the XVIIth century as a fully deterministic
      theory in the form of Newtonian mechanics, the use of probabilistic arguments
      turned out later on to be unavoidable. Three main situations can be
      distinguished. (1) When the number of degrees of freedom is very large, on the
      order of Avogadro's number, a detailed dynamical description is not possible, and
      in fact not useful: we do not care about the velocity of a particular molecule in
      a gas, all we need is the probability distribution of the velocities. This
      statistical description introduced by Maxwell and Boltzmann allows us to recover
      equilibrium thermodynamics, gives a microscopic interpretation of entropy and
      underlies our understanding of irreversibility. (2) Even when the number of
      degrees of freedom is small (but larger than three) sensitivity to initial
      conditions of chaotic dynamics makes determinism irrelevant in practice, because
      we cannot control the initial conditions with infinite accuracy. Although die
      tossing is in principle predictable, the approach to chaotic dynamics in some
      limit implies that our ignorance of initial conditions is translated into a
      probabilistic description: each face comes up with probability 1/6. (3) As is
      well-known, quantum mechanics is incompatible with determinism. However, quantum
      probabilities differ in an essential way from the probabilities introduced
      previously: it has been shown from the work of John Bell that quantum
      probabilities are intrinsic and cannot be given an ignorance interpretation based
      on a hypothetical deeper level of description.

PMID- 22609726
TI  - The frequency and treatment of dural tears and cerebrospinal fluid leakage in 266
      patients with thoracic myelopathy caused by ossification of the ligamentum
      flavum.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: To perform a single-institution
      analysis of incidence, treatment, and clinical outcome in patients with thoracic
      ossification of the ligamentum flavum (OLF) who experienced dural tears and
      cerebrospinal fluid (CSF) leakage. SUMMARY OF BACKGROUND DATA: There is a paucity
      of clinical reports focusing on dural tears and CSF leakage after thoracic OLF
      surgery. Because dural adhesion and dural ossification are common features of
      thoracic OLF, the incidence of CSF leakage in OLF patients is high and represents
      a significant clinical challenge. METHODS: A total of 266 patients with thoracic
      OLF were admitted to our hospital from 1995 to 2011. Each patient's medical
      records were reviewed to identify cases of dural tears and CSF leakage.
      Information on therapeutic strategy used to repair the dural tears and
      complications related to CSF leakage was extracted. RESULTS: The incidence of
      dural tears and CSF leakage in OLF patients was 32% (85/266). The incidence of
      dural ossification was 25.2%. The dural tears were repaired with a range of
      materials, including gelatin sponge, muscle/fascia, artificial dura, silk suture,
      and fibrin glue. The intraoperative repair procedure did not resolve CSF leakage
      in 65 cases, and 16 of those cases experienced complications related to the
      continued CSF leakage, including CSF pseudocyst, wound dehiscence, and
      meningitis. Fifty-eight patients with CSF leakage were eventually cured by a
      series of comprehensive treatments, which included prone position, continuous
      pressure by sandbag, ultrasound-guided puncture, and aspiration. Only 7 patients
      required reoperation. CONCLUSION: Dural ossification was the main reason for
      dural tears. In all, 78 of the 85 patients with CSF leakage or dural tear were
      successfully cured. The success rate was 91.8%, which indicated that a series of
      comprehensive treatments was an effective strategy to treat these patients.

PMID- 22609728
TI  - Development and validation of the Dutch brief form of the Multidimensional
      Personality Questionnaire (MPQ-BF-NL).
AB  - This study describes the development and psychometric properties of the Dutch
      brief form of the Multidimensional Personality Questionnaire (MPQ-BF-NL).
      Representative samples from the Netherlands (N = 1,055) and the United States (N
      = 1,153) and a Dutch student sample (N = 987) were used for development, cross-
      and external validation, respectively. The authors' strategy for item selection
      and scale validation replicated the development of the U.S. brief form (MPQ-BF).
      Internal consistencies were generally good and comparable to the U.S. version, as
      were correlations with the U.S. full-length scales and higher order structure.
      Moreover, convergent and divergent patterns were consistent with prediction, with
      Positive Emotionality related to social and activating behavior, Negative
      Emotionality to anxiety, and Constraint to reversed impulsivity and externalizing
      behaviors. In sum, the MPQ-BF-NL provides the Dutch-Flemish language area with a
      personality inventory well suited for both psychopathology research and clinical
      practice and offers new opportunities for fundamental and cross-cultural studies
      on personality. 

PMID- 22609727
TI  - Prognostic factors and survival in primary malignant astrocytomas of the spinal
      cord: a population-based analysis from 1973 to 2007.
AB  - STUDY DESIGN: Observational cross-sectional study. OBJECTIVE: Using data from the
      population-based cancer registries of the Surveillance, Epidemiology and End
      Results (SEER) program, we analyzed demographic features, tumor and treatment
      characteristics, as well as survival rates in patients with primary malignant
      astrocytomas of the spinal cord (PMASC). SUMMARY OF BACKGROUND DATA: PMASC is a
      rare neoplasm and is considered to carry the same dismal outcome as their
      cerebral counterparts. Our current knowledge is incomplete, and understanding the
      epidemiology, diagnosis, and optimal treatment still poses challenges. METHODS:
      The SEER data from 1973 to 2007 were reviewed for pathologically confirmed
      primary anaplastic astrocytomas (AA) and glioblastomas of the spinal cord
      (C72.0). We compared the clinical features and outcomes of the cohort in uni- and
      multivariate fashion. Survival was calculated and compared using Kaplan-Meier
      curves and log-rank analysis. RESULTS: Our search criteria retrieved 135 patients
      diagnosed with PMASC. The median survival for PMASC was 13 months with 1-, 2-,
      and 5-year survival rates of 51.8%, 32.2%, and 18.7%. Patient diagnosed with AA
      had a median survival time of 17 months versus 10 months in patients diagnosed
      with glioblastomas. Adult patients observed markedly prolonged survival compared
      with the pediatric group, with a 16-month versus 9-month median survival,
      respectively. Multivariate analysis revealed age at diagnosis, pediatric and
      adult age groups, sex, tumor histology, and extent of resection as significant
      predictors of survival. Interestingly, outcomes did not significantly change
      throughout the last decades or by receiving radiotherapy. CONCLUSION: Outcome for
      patients diagnosed with PMASC remains poor and presents an ongoing challenge for
      professionals in the field of neurospinal medicine and surgery. In our analyses
      of AA, adult patients, males, and patients undergoing radical resections were
      associated with increased survival. However, incidence of these lesions is low;
      hence, building strong collaborative, interdisciplinary, and multi-institutional
      study groups is necessary to define the optimal treatment of PMASC.

PMID- 22609729
TI  - Ovary-specific novel peroxisome proliferator activated receptors-gamma
      transcripts in buffalo.
AB  - In the present study, we describe the isolation and characterization of the
      transcripts encoding peroxisome proliferator-activated receptor gamma (PPARgamma1
      and PPARgamma2) in buffalo ovary. 5' RACE experiments and sequence analysis
      showed that these transcripts (PPARgamma1a, PPARgamma1b and PPARgamma2) were
      transcribed by the different promoter usage and alternative splicing of terminal
      5'-exon. The distribution of these isoforms of PPARgamma transcripts in different
      tissues (ovary, mammary gland, spleen, liver, lung, adipose tissue) was
      investigated using quantitative real time analysis. Tissue- and transcript
      specific expression analyses showed that a transcript, transcribed from distal
      promoter, not only expressed preferentially in ovary but contributes
      predominantly to PPAR gamma expression in ovary. Western blot analysis of both,
      in vivo and in vitro, experiments also supported that PPARgamma1 predominantly
      expressed in ovary. In buffalo granulosa cells culture, the isolated transcripts
      were found to be up-regulated by both natural (CLA) and synthetic (Rosiglitazone)
      ligands and effect was reversed by PPARgamma antagonist GW9662. In conclusion,
      the present study identified an ovary-specific novel transcript, transcribed by
      distal promoter, predominantly expressed in ovary which could have functional
      relevance in buffalo ovary.

PMID- 22609730
TI  - Recombinant interferon-gamma activates immune responses against Edwardsiella
      tarda infection in the olive flounder, Paralichthys olivaceus.
AB  - Interferon gamma (IFN-gamma) is a cytokine that plays a very important role in
      defining Th1 immune response in all vertebrates. In this study, recombinant IFN
      gamma (rIFN-gamma) from the olive flounder (Paralichthys olivaceus) was produced
      in an Escherichia coli system using a pET expression vector. Stimulation of whole
      kidney leukocytes (immune-related cells) in vitro with the resulting rIFN-gamma
      significantly induced the gene expression of interleukin-1beta (IL-1beta), signal
      transducer and activator of transcription 1 (STAT1), CXCL13-like chemokine
      (CXCL13), and IFN-gamma. rIFN-gamma also weakly induced the expression of IL
      1beta, tumor necrosis factor-alpha (TNF-alpha), CXCL13, and IFN-gamma in olive
      flounder-derived HINAE (non-immune) cells. The effects of rIFN-gamma against
      Edwardsiella tarda infection in vivo were assessed by intraperitoneally injecting
      a mixture of rIFN-gamma (100 ng) and E. tarda (1 * 10(5) CFU/ml) into the olive
      flounder. The survival rate in the rIFN-gamma-injected group was 60% compared to
      0% in the group treated with E. tarda only, demonstrating that olive flounder IFN
      gamma is effective in reinforcing immune responses and preventing against
      edwardsiellosis.

PMID- 22609731
TI  - The controlled relay of multiple protons required at the active site of
      nitrogenase.
AB  - The enzyme nitrogenase, when reducing natural and unnatural substrates, requires
      large numbers of protons per chemical catalytic cycle. The active face of the
      catalytic site (the FeMo-cofactor, FeMo-co) is situated in a protein domain which
      is largely hydrophobic and anhydrous, and incapable of serial provision of
      multiple protons. Through detailed analysis of the high quality protein crystal
      structures available the characteristics of a chain of water molecules leading
      from the protein surface to a key sulfur atom (S3B) of FeMo-co are described. The
      first half of the water chain from the surface inwards is branched, slightly
      variable, and able to accommodate exogenous small molecules: this is dubbed the
      proton bay. The second half, from the proton bay to S3B, is comprised of a single
      chain of eight hydrogen bonded water molecules. This section is strictly
      conserved, and is intimately involved in hydrogen bonds with homocitrate, an
      essential component that chelates Mo. This is the proton wire, and a detailed
      Grotthuss mechanism for serial translocation of protons through this proton wire
      to S3B is proposed. This controlled serial proton relay from the protein surface
      to S3B is an essential component of the intramolecular hydrogenation paradigm for
      the complete chemical mechanisms of nitrogenase. Each proton reaching S3B,
      instigated by electron transfer to FeMo-co, becomes a hydrogen atom that migrates
      to other components of the active face of FeMo-co and to bound substrates and
      intermediates, allowing subsequent multiple proton transfers along the proton
      wire. Experiments to test the proposed mechanism of proton supply are suggested.
      The water chain in nitrogenase is comparable with the purported proton pumping
      pathway of cytochrome c oxidase.

PMID- 22609732
TI  - Why is partial-breast irradiation still investigational.
AB  - The investigational nature of partial breast irradiation (PBI) remains an area of
      controversy in the field of breast radiotherapy. While we have a long track
      record of conducting and strongly supporting the research in this area, we have
      chosen the more cautious approach of continuing to offer PBI only as part of a
      trial, open to selected breast cancer patients at low risk of local recurrence.
      This position reflects the fact that existing whole breast radiotherapy has
      revealed very successful in controlling local recurrences and it remains the
      safest choice for the patient. Our thinking has been reinforced by the recent
      data linking the prevention of recurrence to long term breast cancer survival:
      until more is known about PBI safety, its indiscriminate use may deprive some
      women from their best chance of fighting breast cancer. Considerations regarding
      the correct interpretation of the available evidence in view of the still limited
      duration of follow up and of the pattern of local recurrence of breast cancer
      sustain our position that PBI can be offered only in the context of a clinical
      trial. Unfortunately, more time and data are warranted for PBI to be legitimately
      recognized a standard radiotherapy approach in breast conservation therapy.

PMID- 22609733
TI  - ACR Appropriateness Criteria(r) follow-up and retreatment of brain metastases.
AB  - Multiple options for retreatment are available, which include whole-brain
      radiation therapy, stereotactic radiosurgery, surgery, chemotherapy, and
      supportive care. Size, number, timing, location, histology, performance status,
      and extracranial disease status all need to be carefully considered when choosing
      a treatment modality. There are no randomized trials examining the retreatment of
      brain metastases. Repeat whole-brain radiation has been examined in a single
      institution experience, showing the potential for clinical responses in selected
      patients. Local control rates as high as 91% using stereotactic radiosurgery for
      relapses after whole-brain radiation are reported. Surgery can be indicated in
      progressive and/or hemorrhagic lesions causing mass effect. The role of
      chemotherapy in the recurrent setting is limited but some agents may have
      activity on the basis of experiences on a smaller scale. Supportive care
      continues to be an important option, especially in those with a poor prognosis.
      Follow-up for brain metastases patients is discussed, examining the modality,
      frequency of imaging, and imaging options in differentiating treatment effect
      from recurrence. The American College of Radiology Appropriateness Criteria are
      evidence-based guidelines for specific clinical conditions that are reviewed
      every 2 years by a multidisciplinary expert panel. The guideline development and
      review include an extensive analysis of the current medical literature from peer
      reviewed journals and the application of a well-established consensus methodology
      (modified Delphi) to rate the appropriateness of imaging and treatment procedures
      by the panel. In instances where evidence is lacking or not definitive, expert
      opinion may be used to recommend imaging or treatment.

PMID- 22609734
TI  - Do G-CSF schedules make a difference?

PMID- 22609735
TI  - A cluster of Plasmodium vivax malaria in an expedition group to Ethiopia:
      prophylactic efficacy of atovaquone/proguanil on liver stages of P. vivax.
AB  - OBJECTIVES: Complete prevention of malaria especially Plasmodium falciparum is
      the goal of prophylaxis. A survey, designed to ascertain reasons behind the
      choice of malaria prophylaxis, compliance and side effects, and to gather data on
      acquired malaria, identified a cluster of Plasmodium vivax infection in a cohort
      of 33 who travelled to Ethiopia on a scientific expedition. METHODS: A
      questionnaire based survey of travellers who took part in a scientific survey and
      rafting expedition in Ethiopia between October and December 2005 on their return
      from the expedition and two years later. RESULTS: 31 of 33 subjects completed the
      survey fully. Evidence was obtained on factors influencing choice of, and
      adherence to prophylaxis and the incidence and type of malaria related to
      prophylaxis. Over the two year follow up period 32% of travellers developed P.
      vivax malaria. Of those taking Mefloquine and Doxycycline 50% and 66%
      respectively developed malaria, compared to none taking Atovaquone/Proguanil as
      prophylaxis. Awareness and management of malaria was inadequate in several cases.
      Failure to use Primaquine led to second relapses. CONCLUSIONS: Within this
      cluster, prophylaxis against P. falciparum was successful. Widespread failure of
      prophylaxis against P. vivax malaria was documented despite the use of
      recommended regimes of known efficacy against the parasite. Atovaquone/Proguanil
      had the least side effects and afforded the highest protection.
      Atovaquone/Proguanil may provide previously unrecognised protection against liver
      stages of P. vivax.

PMID- 22609736
TI  - Optimization of an extracellular zinc-metalloprotease (SVP2) expression in
      Escherichia coli BL21 (DE3) using response surface methodology.
AB  - In this work, SVP2 from Salinivibrio proteolyticus strain AF-2004, a zinc
      metalloprotease with suitable biotechnological applications, was cloned for
      expression at high levels in Escherichia coli with the intention of changing
      culture conditions to generate a stable extracellular enzyme extract. The
      complete ORF of SVP2 gene was heterologously expressed in E. coli BL21 (DE3) by
      using pQE-80L expression vector system. In initial step, the effect of seven
      factors include: incubation temperature, peptone and yeast extract concentration,
      cell density (OD600) before induction, inducer (IPTG) concentration, induction
      time, and Ca(2+) ion concentrations on extracellular recombinant SVP2 expression
      and stability were investigated. The primary results revealed that the IPTG
      concentration, Ca(2+) ion concentration and induction time are the most important
      effectors on protease secretion by recombinant E. coli BL21. Central composite
      design experiment in the following showed that the maximum protease activity (522
      U/ml) was achieved in 0.0089 mM IPTG for 24h at 30  degrees C, an OD600 of 2,
      0.5% of peptone and yeast extract, and a Ca(2+) ion concentration of 1.3 mM. The
      results exhibited that the minimum level of IPTG concentration along with high
      cell density and medium level of Ca(2+) with prolonged induction time provided
      the best culture condition for maximum extracellular production of heterologous
      protease SVP2 in E. coli expression system.

PMID- 22609737
TI  - Targeting the lateral interactions of transmembrane domain 5 of Epstein-Barr
      virus latent membrane protein 1.
AB  - The lateral transmembrane protein-protein interaction has been regarded as
      "undruggable" despite its importance in many biological processes. The homo
      trimerization of transmembrane domain 5 (TMD-5) of latent membrane protein 1 (LMP
      1) is critical for the constitutive oncogenic activation of the Epstein-Barr
      virus (EBV). Herein, we report a small molecule agent, NSC 259242 (compound 1),
      to be a TMD-5 self-association disruptor. Both the positively charged
      acetimidamide functional groups and the stilbene backbone of compound 1 are
      essential for its inhibitory activity. Furthermore, cell-based assays revealed
      that compound 1 inhibits full-length LMP-1 signaling in EBV infected B cells.
      These studies demonstrated a new strategy for identifying small molecule
      disruptors for investigating transmembrane protein-protein interactions.

PMID- 22609738
TI  - Evaluation of the role of the glutathione redox cycle in Cu(II) toxicity to green
      algae by a chiral perturbation approach.
AB  - The effect of heavy metal toxicity on the environment is usually linked to
      changes in the glutathione redox cycle and oxidative damage as causative events.
      However, it is unknown whether changes in the glutathione redox cycle are a cause
      or result of Cu(II) toxicity. Herein, a new chiral perturbation strategy
      involving a chiral herbicide, dichlorprop (DCPP), as a perturbation factor was
      used. According to the dose-response fitting curve of DCPP and the combination
      with Cu(II), 40 MUM (R)-DCPP and (S)-DCPP, whose toxicities were low enough to
      not significantly perturb the Cu(II) toxicity, were selected as the chiral
      perturbation factor. When Scenedesmus obliquus was incubated with the chiral
      perturbation factor and 10 MUM Cu(II), chiral perturbation was observed in the
      chlorophyll content and the PAM chlorophyll fluorescence. Then, the role of the
      glutathione redox cycle in the toxicity of Cu(II) was evaluated with the chiral
      perturbation approach. The results revealed that the GSH differences in algae
      cells exposed to (R)-DCPP or (S)-DCPP were well correlated with the differences
      in the production of reactive oxygen species (ROS) after exposure to the two
      enantiomers. When (R)-DCPP or (S)-DCPP was added with Cu(II) to the algae
      culture, treatment with (R)-DCPP-Cu resulted in a decrease in the GSH content in
      algae cells compared to the control, whereas treatment with (S)-DCPP-Cu resulted
      in an increase in the GSH. The GSH/GSSG ratio and GR activity also showed similar
      enantioselectivities. The enantioselectivities would not exist if the changes of
      in glutathione redox cycle were the cause. Therefore, these data provide indirect
      evidence that ROS induced cell toxicity of Cu is a causative event, which results
      in the response of the glutathione redox cycle. These results also provided an
      implication that before sustainable detoxification strategies for heavy metal
      pollutants were proposed, it is better that the roles of ROS production and
      glutathione redox cycle are elucidated. In this case, the chiral perturbation
      strategy may be a good choice.

PMID- 22609739
TI  - Recreating the seawater mixture composition of HOCs in toxicity tests with
      Artemia franciscana by passive dosing.
AB  - The toxicity testing of hydrophobic organic compounds (HOCs) in aquatic media is
      generally challenging, and this is even more problematic for mixtures. The
      hydrophobic properties of these compounds make them difficult to dissolve, and
      subsequently to maintain constant exposure concentrations. Evaporative and
      sorptive losses are highly compound-specific, which can alter not only total
      concentrations, but also the proportions between the compounds in the mixture.
      Therefore, the general aim of this study was to explore the potential of passive
      dosing for testing the toxicity of a PAH mixture that recreates the mixture
      composition found in seawater from a coastal area of Spain, the Bay of Algeciras.
      First, solvent spiking and passive dosing were compared for their suitability to
      determine the acute toxicity to Artemia franciscana nauplii of several PAHs at
      their respective solubility limits. Second, passive dosing was applied to
      recreate the seawater mixture composition of PAHs measured in a Spanish
      monitoring program, to test the toxicity of this mixture at different levels.
      HPLC analysis was used to confirm the reproducibility of the dissolved exposure
      concentrations for the individual PAHs and mixtures. This study shows that
      passive dosing has some important benefits in comparison with solvent spiking for
      testing HOCs in aquatic media. These include maintaining constant exposure
      concentrations, leading to higher reproducibility and a relative increase in
      toxicity. Passive dosing is also able to faithfully reproduce real mixtures of
      HOCs such as PAHs, in toxicity tests, reproducing both the levels and proportions
      of the different compounds. This provides a useful approach for studying the
      toxicity of environmental mixtures of HOCs, both with a view to investigating
      their toxicity but also for determining safety factors before such mixtures
      result in detrimental effects.

PMID- 22609740
TI  - BDE-47 disrupts axonal growth and motor behavior in developing zebrafish.
AB  - Polybrominated diphenyl ethers (PBDEs) are ubiquitous environmental pollutants
      detected in a wide variety of environmental matrixes and pose a significant
      public health concern. 2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) is one of the
      most predominant PBDE congeners in environmental media, biota and human tissues.
      However, few studies have explored the BDE-47 developmental neurotoxicity and
      underlying mechanisms. In this study, zebrafish (Danio rerio) embryos were
      waterborne exposed to BDE-47 at 1.25, 5, 20 MUM starting from 6h post
      fertilization (hpf). Motor behavior development and swimming behavior in response
      to light-to-dark photoperiod stimulation were studied at various developmental
      stages. Our data indicate that BDE-47 exposure significantly affected spontaneous
      movement, decreased touch response and free swimming speed, altered larvae
      swimming behavior in response to light stimulation in developing zebrafish.
      Consistent with these motor deficits, BDE-47 significantly inhibited axonal
      growth of primary and secondary motor neurons during the early developmental
      stages, suggesting the functional relevance of structural changes. Our findings
      demonstrate that the altered patterns of neuronal connectivity may contribute to
      motor behavior deficits, indicating the relevance of zebrafish as a model for
      studying toxicant developmental neurotoxicity.

PMID- 22609741
TI  - Craniofacial abnormalities and altered wnt and mmp mRNA expression in zebrafish
      embryos exposed to gasoline oxygenates ETBE and TAME.
AB  - Gasoline additives ethyl tert butyl ether (ETBE) and tertiary amyl methyl ether
      (TAME) are used world wide, but the consequence of developmental exposure to
      these hydrophilic chemicals is unknown for aquatic vertebrates. The effect of
      ETBE and TAME on zebrafish embryos was determined following OECD 212 guidelines,
      and their toxicity was compared to structurally related methyl tert-butyl ether
      (MTBE), which is known to target developing vasculature. LC50s for ETBE and TAME
      were 14 mM [95% CI=10-20] and 10 mM [CI=8-12.5], respectively. Both chemicals
      caused dose dependent developmental lesions (0.625-10 mM), which included
      pericardial edema, abnormal vascular development, whole body edema, and
      craniofacial abnormalities. The lesions were suggestive of a dysregulation of WNT
      ligands and matrix metalloproteinase (MMP) protein families based on their roles
      in development. Exposure to 5 mM ETBE significantly (p<=0.05) decreased relative
      mRNA transcript levels of mmp-9 and wnt3a, while 2.5 and 5 mM TAME significantly
      decreased wnt3a, and wnt8a. TAME also significantly decreased mmp-2 and -9 mRNA
      levels at 5mM. ETBE and TAME were less effective in altering the expression of
      vascular endothelial growth factor-a and -c, which were the only genes tested
      that were significantly decreased by MTBE. This is the first study to
      characterize the aquatic developmental toxicity following embryonic exposure to
      ETBE and TAME. Unlike MTBE, which specifically targets angiogenesis, ETBE and
      TAME disrupt multiple organ systems and significantly alter the mRNA transcript
      levels of genes required for general development.

PMID- 22609742
TI  - Extensive ligand-based modeling and in silico screening reveal nanomolar
      inducible nitric oxide synthase (iNOS) inhibitors.
AB  - Inducible nitric oxide synthase (iNOS) has been implicated in a variety of
      diseases prompting several attempts to discover and optimize new iNOS inhibitors.
      Accordingly, we explored the pharmacophoric space of 143 iNOS inhibitors.
      Subsequently, genetic algorithm and multiple linear regression analysis were
      employed to select an optimal combination of pharmacophoric models and 2D
      physicochemical descriptors to produce self-consistent quantitative structure
      activity relationship (QSAR) of optimal predictive potential (correlation
      coefficient r115=0.83, F=23.92, r2(LOO)=0.61, r2(PRESS) against 28 external test
      inhibitors=0.51). Two orthogonal pharmacophores emerged in the QSAR equation
      suggesting the existence of at least two binding modes accessible to ligands
      within iNOS binding pocket. The pharmacophores were validated by comparison with
      crystallographic complexes of active iNOS inhibitors and receiver operating
      characteristic (ROC) curves analysis. We employed the pharmacophoric models and
      associated QSAR equation to screen the national cancer institute list of
      compounds (NCI). Three low nanomolar inhibitors were identified. The most potent
      hit exhibited irreversible inhibition of iNOS with IC50 value of 1.4 nM.

PMID- 22609743
TI  - Dual inhibition of chaperoning process by taxifolin: molecular dynamics
      simulation study.
AB  - Hsp90 (heat shock protein 90), a molecular chaperone, stabilizes more than 200
      mutated and over expressed oncogenic proteins in cancer development. Cdc37 (cell
      division cycle protein 37), a co-chaperone of Hsp90, has been found to facilitate
      the maturation of protein kinases by acting as an adaptor and load these kinases
      onto the Hsp90 complex. Taxifolin (a natural phytochemical) was found to bind at
      ATP-binding site of Hsp90 and stabilized the inactive "open" or "lid-up"
      conformation as evidenced by molecular dynamic simulation. Furthermore, taxifolin
      was found to bind to interface of Hsp90 and Cdc37 complex and disrupt the
      interaction of residues of both proteins which were essential for the formation
      of active super-chaperone complex. Thus, taxifolin was found to act as an
      inhibitor of chaperoning process and may play a potential role in the cancer
      chemotherapeutics.

PMID- 22609744
TI  - Activation of the unfolded protein response contributed to the selective
      cytotoxicity of oroxylin A in human hepatocellular carcinoma HepG2 cells.
AB  - Hepatocellular carcinoma (HCC) is a refractory malignancy with a high incidence
      and large mortality. Current strategy for the chemotherapy of HCC focuses on
      developing agents with better efficacy and lower toxicity. In this study, we
      demonstrated that the natural flavonoid oroxylin A preferentially inhibited the
      viability of HCC cell line HepG2 but not the normal hepatic cell line L02. In
      HepG2 but not L02 cells, oroxylin A induced substantial production of
      intracellular H2O2 and inordinate activation of the PERK-eIF2alpha-ATF4-CHOP
      branch of the unfolded protein response (UPR) pathway, which resulted in the
      induction of TRB3 and causal reduction of p-AKT1/2/3 (Ser473). Moreover, these
      effects were eliminated by either the stable knockdown of CHOP or the
      pretreatment and then co-incubation with the specific H2O2 scavenger catalase.
      These results indicated that the H2O2-triggered overactivation of the UPR pathway
      and causal inactivation of AKT signaling contributed to the preferential
      cytotoxicity of oroxylin A in malignant HepG2 cells. Therefore, present study
      proposed an underlying molecular mechanism that implicated the selective
      antitumor effect of oroxylin A and recommended oroxylin A as a prospect for
      improving the current chemotherapeutic strategy for the treatment of HCC.

PMID- 22609746
TI  - Topological singularities and symmetry breaking in development.
AB  - The review presents a topological interpretation of some morphogenetic events
      through the use of well-known mathematical concepts and theorems. Spatial
      organization of the biological fields is analyzable in topological terms.
      Topological singularities inevitably emerging in biological morphogenesis are
      retained and transformed during pattern formation. It is the topological language
      that can provide strict and adequate description of various phenomena in
      developmental and evolutionary transformations. The relationship between local
      and global orders in metazoan development, i.e., between local morphogenetic
      processes and integral developmental patterns, is established. A topological
      inevitability of some developmental events through the use of classical
      topological concepts is discussed. This methodology reveals a topological
      imperative as a certain set of topological rules that constrains and directs
      embryogenesis. A breaking of spatial symmetry of preexisting pattern plays a
      critical role in biological morphogenesis in development and evolution.

PMID- 22609747
TI  - Prognostic significance of systematic lymphadenectomy as part of primary
      debulking surgery in patients with advanced ovarian cancer.
AB  - OBJECTIVE: The objective of this study was to evaluate the impact of systematic
      pelvic and para-aortic lymphadenectomy on survival in patients with advanced
      ovarian cancer. METHODS: We retrospectively analyzed the data of 189 consecutive
      patients with FIGO stage IIIC ovarian cancer between 2000 and 2011, who underwent
      primary cytoreductive surgery followed by platinum- and taxane-based
      chemotherapy. All patients were classified into two groups - patients who
      underwent systematic pelvic and para-aortic lymphadenectomy and those who did
      not. Progression-free (PFS) and overall survival (OS) times were analyzed using
      Kaplan-Meier method and Cox proportional hazards model. RESULTS: Patients who
      underwent systematic lymphadenectomy had significantly improved PFS (22 versus 9
      months, p<0.01) and OS (66 versus 40 months, p<0.01). In patients with no gross
      residual disease (NGR) or residual disease 0.1-1cm (GR-1), the median OS time of
      those who had lymphadenectomy was significantly longer than those who did not (86
      versus 46 months, p=0.02). However, in patients with residual disease >1cm (GR
      B), there was no significant difference in OS according to lymphadenectomy (39
      versus 40 months, p=0.50). Among patients with NGR, the median OS time of those
      who underwent systematic lymphadenectomy was significantly longer than those who
      did not undergo lymphadenectomy (not yet reached [>96] and 56 months, p<0.01). No
      significant difference of OS between patients with and without lymphadenectomy
      was observed in the subgroup of patients with GR-1 (50 versus 38 months, p=0.44).
      The performance of lymphadenectomy was a statistically significant and
      independent predictor of improved OS in addition to the status of residual
      disease and the performance of radical cytoreductive procedures (hazard ratio,
      0.34; [95% CI, 0.23-0.52]; p<0.01). CONCLUSIONS: Systematic lymphadenectomy may
      have a therapeutic value and be significantly associated with improved survival
      in stage IIIC ovarian cancer patients with grossly no visible residual disease.

PMID- 22609748
TI  - Private equity ownership and nursing home financial performance.
AB  - BACKGROUND: Private equity has acquired multiple large nursing home chains within
      the last few years; by 2009, it owned nearly 1,900 nursing homes. Private equity
      is said to improve the financial performance of acquired facilities. However, no
      study has yet examined the financial performance of private equity nursing homes,
      ergo this study. PURPOSE: The primary purpose of this study is to understand the
      financial performance of private equity nursing homes and how it compares with
      other investor-owned facilities. It also seeks to understand the approach favored
      by private equity to improve financial performance-for instance, whether they
      prefer to cut costs or maximize revenues or follow a mixed approach.
      METHODOLOGY/APPROACH: Secondary data from Medicare cost reports, the Online
      Survey, Certification and Reporting, Area Resource File, and Brown University's
      Long-term Care Focus data set are combined to construct a longitudinal data set
      for the study period 2000-2007. The final sample is 2,822 observations after
      eliminating all not-for-profit, independent, and hospital-based facilities.
      Dependent financial variables consist of operating revenues and costs, operating
      and total margins, payer mix (census Medicare, census Medicaid, census other),
      and acuity index. Independent variables primarily reflect private equity
      ownership. The study was analyzed using ordinary least squares, gamma
      distribution with log link, logit with binomial family link, and logistic
      regression. FINDINGS: Private equity nursing homes have higher operating margin
      as well as total margin; they also report higher operating revenues and costs. No
      significant differences in payer mix are noted. PRACTICE IMPLICATIONS: Results
      suggest that private equity delivers superior financial performance compared with
      other investor-owned nursing homes. However, causes for concern remain
      particularly with the long-term financial sustainability of these facilities.

PMID- 22609749
TI  - Role of surface proteins SspA and SspB of Streptococcus gordonii in innate
      immunity.
AB  - Streptococcus gordonii, a normal inhabitant of the human oral cavity, is a
      potential live vaccine vehicle. Several pathogen-associated molecular patterns
      from S. gordonii that are recognized by antigen-presenting cells have recently
      been identified. In this study, we have identified that the cell-wall-anchored
      proteins SspA and SspB are immunostimulatory components of S. gordonii. SspA and
      SspB are members of the antigen I/II family of proteins widely expressed by
      viridans oral streptococci. The results showed that the mutant (OB219) lacking
      SspA and SspB had a reduced ability to induce cytokine/chemokine production in
      epithelial cells and bone-marrow-derived dendritic cells as compared with the
      parent strain (DL1). Purified SspA induced interleukin-6 and monocyte chemotatic
      protein-1 production from human lung epithelial A549 cells. The induction could
      be inhibited by a function-blocking anti-beta1 integrin mAb and the purified SspA
      could bind to beta1 integrin precoated on microtitre plates, suggesting that the
      induction was effected by SspA-beta1 integrin interactions. The role of SspA and
      SspB in innate immunity was further demonstrated in a mouse intranasal challenge
      experiment, which showed that the clearance of OB219, the recruitment of
      neutrophils (as indicated by myeloperoxidase activity), and chemokine and
      cytokine production in the lungs of OB219-inoculated mice were delayed or reduced
      as compared with the DL1-inoculated mice. In addition to the above, S. gordonii
      OB219 was more sensitive to polymyxin, nisin and histatin-5 than DL1, suggesting
      that SspA and SspB also play a role in susceptibility to cationic antimicrobial
      peptides. Collectively, the results indicate that SspA and SspB are
      immunostimulatory components of S. gordonii and play an important role in
      modulating the host's innate immunity.

PMID- 22609750
TI  - A luminescent reporter evidences active expression of Ralstonia solanacearum type
      III secretion system genes throughout plant infection.
AB  - Although much is known about the signals that trigger transcription of virulence
      genes in plant pathogens, their prevalence and timing during infection are still
      unknown. In this work, we address these questions by analysing expression of the
      main pathogenicity determinants in the bacterial pathogen Ralstonia solanacearum.
      We set up a quantitative, non-invasive luminescent reporter to monitor in planta
      transcription from single promoters in the bacterial chromosome. We show that the
      new reporter provides a real-time measure of promoter output in vivo - either
      after re-isolation of pathogens from infected plants or directly in situ - and
      confirm that the promoter controlling exopolysaccharide (EPS) synthesis is active
      in bacteria growing in the xylem. We also provide evidence that hrpB, the master
      regulator of type III secretion system (T3SS) genes, is transcribed in
      symptomatic plants. Quantitative RT-PCR assays demonstrate that hrpB and type III
      effector transcripts are abundant at late stages of plant infection, suggesting
      that their function is required throughout disease. Our results challenge the
      widespread view in R. solanacearum pathogenicity that the T3SS, and thus
      injection of effector proteins, is only active to manipulate plant defences at
      the first stages of infection, and that its expression is turned down when
      bacteria reach high cell densities and EPS synthesis starts.

PMID- 22609751
TI  - Cloning and functional analysis of the genes coding for 4-aminobenzenesulfonate
      3,4-dioxygenase from Hydrogenophaga sp. PBC.
AB  - The gene coding for the oxygenase component, sadA, of 4-aminobenzenesulfonate (4
      ABS) 3,4-dioxygenase in Hydrogenophaga sp. PBC was previously identified via
      transposon mutagenesis. Expression of wild-type sadA in trans restored the
      ability of the sadA mutant to grow on 4-ABS. The inclusion of sadB and sadD,
      coding for a putative glutamine-synthetase-like protein and a plant-type
      ferredoxin, respectively, further improved the efficiency of 4-ABS degradation.
      Transcription analysis using the gfp promoter probe plasmid showed that sadABD
      was expressed during growth on 4-ABS and 4-sulfocatechol. Heterologous expression
      of sadABD in Escherichia coli led to the biotransformation of 4-ABS to a
      metabolite which shared a similar retention time and UV/vis profile with 4
      sulfocatechol. The putative reductase gene sadC was isolated via degenerate PCR
      and expression of sadC and sadABD in E. coli led to maximal 4-ABS
      biotransformation. In E. coli, the deletion of sadB completely eliminated
      dioxygenase activity while the deletion of sadC or sadD led to a decrease in
      dioxygenase activity. Phylogenetic analysis of SadB showed that it is closely
      related to the glutamine-synthetase-like proteins involved in the aniline
      degradation pathway. This is the first discovery, to our knowledge, of the
      functional genetic components for 4-ABS aromatic ring hydroxylation in the
      bacterial domain.

PMID- 22609752
TI  - Genetic characterization of a complex locus necessary for the transport and
      catabolism of erythritol, adonitol and L-arabitol in Sinorhizobium meliloti.
AB  - The Sinorhizobium meliloti locus necessary for the utilization of erythritol as a
      sole carbon source, contains 17 genes, including genes that encode an ABC
      transporter necessary for the transport of erythritol, as well as the genes
      encoding EryA, EryB, EryC, TpiB and the regulators EryD and EryR (SMc01615).
      Construction of defined deletions and complementation experiments show that the
      other genes at this locus encode products that are necessary for the catabolism
      of adonitol (ribitol) and l-arabitol, but not d-arabitol. These analyses show
      that aside from one gene that is specific for the catabolism of l-arabitol
      (SMc01619, lalA), the rest of the catabolic genes are necessary for both polyols
      (SMc01617, rbtC; SMc01618, rbtB; SMc01622, rbtA). Genetic and biochemical data
      show that in addition to utilizing erythritol as a substrate, EryA is also
      capable of utilizing adonitol and l-arabitol. Similarly, transport experiments
      using labelled erythritol show that adonitol, l-arabitol and erythritol share a
      common transporter (MptABCDE). Quantitative RT-PCR experiments show that
      transcripts containing genes necessary for adonitol and l-arabitol utilization
      are induced by these sugars in an eryA-dependent manner.

PMID- 22609753
TI  - Three inositol dehydrogenases involved in utilization and interconversion of
      inositol stereoisomers in a thermophile, Geobacillus kaustophilus HTA426.
AB  - Geobacillus kaustophilus HTA426, a thermophilic Bacillus-related species,
      utilizes some inositol stereoisomers, including myo-, d-chiro- and scyllo
      inositols (MI, DCI and SI), as sole carbon sources. Within its genome are three
      paralogous genes that possibly encode inositol dehydrogenase. These genes are
      located in tandem within a large gene cluster containing an almost complete set
      of iol genes homologous to genes involved in inositol catabolism in Bacillus
      subtilis. Each of the three plausible inositol dehydrogenases was purified as a
      His(6)-tag fusion. The enzymes exhibited thermophilic activity, each with its own
      characteristic specificity for the inositol stereoisomers and cofactors. Northern
      blot and primer extension analyses revealed that the three enzymes were encoded
      by the same 5 kb polycistronic transcript and were induced simultaneously in the
      presence of MI. HTA426 was subjected to ethyl methanesulfonate (EMS) mutagenesis
      to isolate a mutant strain, PS8, which was not able to utilize MI. In PS8,
      inositol dehydrogenase activity was abolished along with the 5 kb transcript,
      suggesting that any of the three enzymes supports MI-dependent growth. Analysis
      of metabolites in HTA426 cells grown in the presence of MI revealed that
      substantial amounts of DCI and SI appeared intracellularly during the stationary
      phase, while only MI was present in PS8 cells, suggesting that interconversion of
      inositol stereoisomers may involve these three enzymes.

PMID- 22609754
TI  - Identification of amino acids involved in the hydrolytic activity of lipase LipBL
      from Marinobacter lipolyticus.
AB  - The lipolytic enzyme family VIII currently includes only seven members but
      represents a group of lipolytic enzymes with interesting properties. Recently, we
      identified a gene encoding the family VIII lipase LipBL from the halophilic
      bacterium Marinobacter lipolyticus. This enzyme, like most lipolytic enzymes from
      family VIII, possesses two possible nucleophilic serines located in an S-X-X-K
      beta-lactamase motif and a G-X-S-X-G lipase motif. The serine in the S-X-X-K
      motif is a catalytic residue, but the role of serine within the common lipase
      consensus sequence G-X-S-X-G has not yet been systematically studied. Here, the
      previously reported time-intensive procedure for purification of recombinant
      LipBL was replaced by one-step metal-affinity chromatography purification in the
      presence of ATP. Heterologous co-expression of His(6)-tagged LipBL with the
      cytoplasmic molecular chaperones GroEL/GroES was necessary to obtain
      catalytically active LipBL. Site-directed mutagenesis performed to map the active
      site of LipBL revealed that mutation of serine and lysine in the beta-lactamase
      motif (S(72)-M-T-K(75)) to alanine abolished the enzyme activity of LipBL, in
      contrast to mutation of the serine in the lipase consensus motif (S321A).
      Furthermore, mutagenesis was performed to understand the role of the G-X-S-X-G
      motif and other amino acids that are conserved among family VIII esterases. We
      describe how mutations in the conserved G-X-S-X-G motif altered the biochemical
      properties and substrate specificity of LipBL. Molecular modelling results
      indicate the location of the G-X-S(321)-X-G motif in a loop close to the
      catalytic centre of LipBL, presumably representing a substrate-binding site of
      LipBL.

PMID- 22609755
TI  - RsmA post-transcriptionally controls PhbR expression and polyhydroxybutyrate
      biosynthesis in Azotobacter vinelandii.
AB  - In Azotobacter vinelandii the two-component GacS/GacA system is required for
      synthesis of polyhydroxybutyrate (PHB) and of the exopolysaccharide alginate. The
      RsmA protein was shown to interact with the alginate biosynthetic algD mRNA,
      acting as a translational repressor, and GacA was found to activate transcription
      of the rsmZ1 and rsmZ2 genes that encode small RNAs interacting with RsmA to
      counteract its repressor activity. The phbBAC operon encodes the enzymes of PHB
      synthesis and is activated by the transcriptional regulator PhbR. This study
      shows that GacA is required for transcription of one rsmY and seven rsmZ1-rsmZ7
      genes present in the A. vinelandii genome, and that inactivation of rsmA results
      in increased PHB production. Transcriptional and translational phbR-gusA gene
      fusions were used to show that the gacA mutation negatively affected the
      expression of the phbR gene at the translational level. We also demonstrated an
      in vitro interaction of RsmA with RNAs corresponding to phbB and phbR mRNA
      leaders, and showed that the stability of phbR and phbB mRNAs is increased in the
      rsmA mutant. Taken together these results indicate that in A. vinelandii, RsmA
      post-transcriptionally represses the expression of PhbR.

PMID- 22609756
TI  - Distribution of genes involved in sialic acid utilization in strains of
      Haemophilus parasuis.
AB  - Haemophilus parasuis is a porcine respiratory pathogen, well known as the
      aetiological agent of Glasser's disease. H. parasuis comprises strains of
      different virulence, but the virulence factors of this bacterium are not well
      defined. A neuraminidase activity has been previously detected in H. parasuis,
      but the role of sialylation in the virulence of this bacterium has not been
      studied. To explore the relationship between sialic acid (Neu5Ac) and virulence,
      we assessed the distribution of genes involved in sialic acid metabolism in 21 H.
      parasuis strains from different clinical origins (including nasal and systemic
      isolates). The neuraminidase gene nanH, together with CMP-Neu5Ac synthetase and
      sialyltransferase genes neuA, siaB and lsgB, were included in the study.
      Neuraminidase activity was found to be common in H. parasuis isolates, and the
      nanH gene from 12 isolates was expressed in Escherichia coli and further
      characterized. Sequence analysis showed that the NanH predicted protein contained
      the motifs characteristic of the catalytic site of sialidases. While an
      association between the presence of nanH and the different origins of the strains
      was not detected, the lsgB gene was predominantly present in the systemic
      isolates, and was not amplified from any of the nasal isolates tested. Analysis
      of the lipooligosaccharide (LOS) from reference strains Nagasaki (virulent,
      lsgB(+)) and SW114 (non-virulent, lsgB(-)) showed the presence of sialic acid in
      the LOS from the Nagasaki strain, supporting the role of sialylation in the
      virulence of this bacterial pathogen. Further studies are needed to clarify the
      role of sialic acid in the pathogenicity of H. parasuis.

PMID- 22609757
TI  - Immunosuppression with 4SC-101, a novel inhibitor of dihydroorotate
      dehydrogenase, in a rat model of renal transplantation.
AB  - BACKGROUND: 4SC-101 is a novel dihydroorotate dehydrogenase inhibitor and a
      blocker of interleukin (IL)-17 secretion with beneficial effects in experimental
      lupus and inflammatory bowel disease. Its immunomodulatory effect on acute kidney
      rejection is not known; therefore, in this study, the impact of 4SC-101 was
      examined in a rat model of acute kidney rejection. METHODS: The kidneys of Brown
      Norway rats were orthotopically transplanted into bilaterally nephrectomized
      Lewis recipients. Allograft recipients were administered with 4SC-101 at dosages
      of 4, 20, or 60 mg/kg per day, and survival was assessed. In the second setting,
      the animals were harvested 3 or 5 days after transplantation (Tx), and graft
      histologic diagnosis was determined. The effects of 4SC-101 on impaired renal
      function were examined in a model of 5/6 nephrectomy in Lewis rats. RESULTS: The
      recipients treated with 20-mg/kg 4SC-101 showed prolonged survival compared with
      placebo-treated animals (mean+/-SEM, 24+/-9.3 vs. 5.4+/-3 days), paralleled by
      less severe histologic features of acute kidney rejection such as
      interstitial/perivascular infiltration and tubulitis 3 and 5 days after Tx, and a
      lower level of IL-17 messenger RNA 5 days after Tx compared with the placebo
      treated animals. In the 5/6 nephrectomy model, 20-mg/kg 4SC-101 reduced
      proteinuria, glomerulosclerosis, and fibrosis with decreased IL-17 messenger RNA
      expression. CONCLUSIONS: 4SC-101 prolongs survival after Tx, paralleled by
      amelioration of histologic signs of acute rejection. Furthermore, it showed no
      worsening effects on kidney function in a remnant kidney model and even slowed
      the progression of proteinuria and kidney fibrosis. Therefore, 4SC-101 might be a
      promising pharmaceutical agent in Tx medicine for further investigations.

PMID- 22609758
TI  - Methyllycaconitine: a non-radiolabeled ligand for mapping alpha7 neuronal
      nicotinic acetylcholine receptors - in vivo target localization and
      biodistribution in rat brain.
AB  - INTRODUCTION: Reduction of cerebral cortical and hippocampal alpha7 neuronal
      nicotinic acetylcholine receptor (nAChR) density was observed in the Alzheimer's
      disease (AD) and other neurodegenerative diseases. Mapping the subtypes of nAChRs
      with selective ligand by viable, quick and consistent method in preclinical drug
      discovery may lead to rapid development of more effective therapeutic agents. The
      objective of this study was to evaluate the use of methyllycaconitine (MLA) in
      non-radiolabeled form for mapping alpha7 nAChRs in rat brain. METHODS: MLA
      pharmacokinetic and brain penetration properties were assessed in male Wistar
      rats. The tracer properties of MLA were evaluated in rat brain by dose and time
      dependent differential regional distribution studies. Target specificity was
      validated after blocking with potent alpha7 nAChR agonists ABBF, PNU282987 and
      nicotine. High performance liquid chromatography combined with triple quad mass
      spectral detector (LC-MS/MS) was used to measure the plasma and brain tissue
      concentrations of MLA. RESULTS: MLA has shown rapid brain uptake followed by a 3
      5 fold higher specific binding in regions containing the alpha7 nAChRs
      (hypothalamus - 1.60 ng/g), when compared to non-specific regions (striatum -
      0.53 ng/g, hippocampus - 0.46 ng/g, midbrain - 0.37 ng/g, frontal cortex - 0.35
      ng/g and cerebellum - 0.30 ng/g). Pretreatment with potent alpha7 nAChR agonists
      significantly blocked the MLA uptake in hypothalamus. The non-radiolabeled MLA
      binding to brain region was comparable with the alpha7 mRNA localization and
      receptor distribution reported for [(3)H] MLA in rat brain. DISCUSSION: The rat
      pharmacokinetic, brain penetration and differential brain regional distribution
      features favor that MLA is suitable to use in preclinical stage for mapping
      alpha7 nAChRs. Hence, this approach can be employed as an essential tool for
      quicker development of novel selective ligand to map variation in the alpha7
      receptor densities, as well as to evaluate potential new chemical entities
      targeting neurodegenerative diseases.

PMID- 22609759
TI  - Afrocentric cultural values and beliefs: movement beyond the race and ethnicity
      proxy to understand views of diabetes.
AB  - PURPOSE: The purpose of this study was to estimate the benefit of using a
      cultural characteristics scale to help diabetes educators understand how African
      Americans cope with diabetes. Illness representations are influenced by culture.
      Race and ethnicity as a proxy for culture provides an incomplete understanding of
      the mechanism by which cultural values influence representations of diabetes.
      METHODS: A descriptive correlational design was employed by recruiting
      hospitalized adults with type 2 diabetes at 3 metropolitan northeast coast sites.
      The TRIOS Afrocentric cultural characteristics measure and the Illness perception
      Questionnaire were administered by paper-and-pencil to a diverse sample. Black
      race and African American ethnicity was used as a proxy for culture and compared
      to levels of agreement on an Afrocentric cultural scale to determine the relative
      ability to explain variance in illness representations of diabetes. CONCLUSION:
      The TRIOS measure adapted to diabetes care explained variance in illness
      representations of diabetes, while African American ethnicity/black race was not
      able to explain variance in illness representations. Clinicians would benefit
      from considering the degree to which a patient identifies with particular
      cultural characteristics when tailoring interventions to manipulate illness
      representations that are not concordant with biomedical representations.

PMID- 22609760
TI  - Parenting children living with type 1 diabetes: a qualitative study.
AB  - PURPOSE: The purpose of the study was to explore a parent's sense of meaning in
      relation to the parenting of a child with type 1 diabetes. METHODS: A qualitative
      collective case study design was used and 10 interviews conducted with parents of
      children with type 1 diabetes. Recruitment took place through the Winnipeg
      Diabetes Education and Resource for Children and Adolescents and Juvenile
      Diabetes Research Foundation. Categories were identified using qualitative
      content analysis. FINDINGS: Two major categories identified include being like
      everyone else and protecting the children. IMPLICATIONS: Findings indicate that
      there is a need for greater diabetes education in schools. Diabetes educators can
      play a more proactive role in leading school based discussions with children,
      parents, and school staff.

PMID- 22609761
TI  - Training peers to deliver a church-based diabetes prevention program.
AB  - PURPOSE: The purpose of this study was to examine the feasibility and
      acceptability of training peers to function as lifestyle coaches and to deliver a
      church-based lifestyle modification program. METHODS: We recruited 6 African
      American adults to participate in an 8-hour peer lifestyle coach (PLC) training
      program followed by a subsequent 2-hour booster session. The PLC training program
      addressed several key areas, including: (1) developing empowerment-based
      facilitation, active listening, and behavior change skills; (2) learning self
      management strategies (eg, reading food labels, counting calories); (3)
      practicing session delivery; and (4) interpreting clinical lab results. Training
      evaluation was conducted retrospectively (immediately following the delivery of
      the diabetes prevention intervention rather than after the 8-hour training
      session) and measured program satisfaction and efficacy from the perspective of
      participants. RESULTS: Peer lifestyle coaches' confidence levels for performing
      core skills (eg, asking open-ended questions, 5-step behavioral goal-setting
      process) and advanced skills (eg, addressing resistance, discussing sensitive
      topics) were uniformly high. Similarly, PLCs were very satisfied with the length
      of training, balance between content and skills development, and preparation for
      leading group- and individual-based support activities. CONCLUSIONS: Findings
      suggest that it is feasible to customize a PLC training program that is
      acceptable to participants and that equips participants with the knowledge and
      skills to facilitate a church-based diabetes prevention intervention.

PMID- 22609762
TI  - Relative distribution of folate species is associated with global DNA methylation
      in human colorectal mucosa.
AB  - Folate exists as functionally diverse species within cells. Although folate
      deficiency may contribute to DNA hypomethylation in colorectal cancer, findings
      on the association between total folate concentration and global DNA methylation
      have been inconsistent. This study determined global, LINE-1, and Alu DNA
      methylation in blood and colon of healthy and colorectal cancer patients and
      their relationship to folate distribution. Blood and normal mucosa from 112
      colorectal cancer patients and 114 healthy people were analyzed for global DNA
      methylation and folate species distribution using liquid chromatography tandem
      mass spectrometry. Repeat element methylation was determined using end-specific
      PCR. Colorectal mucosa had lower global and repeat element DNA methylation
      compared with peripheral blood (P < 0.0001). After adjusting for age, sex and
      smoking history, global but not repeat element methylation was marginally higher
      in normal mucosa from colorectal cancer patients compared with healthy
      individuals. Colorectal mucosa from colorectal cancer subjects had lower 5
      methyltetrahydrofolate and higher tetrahydrofolate and formyltetrahydrofolate
      levels than blood from the same individual. Blood folate levels should not be
      used as a surrogate for the levels in colorectal mucosa because there are marked
      differences in folate species distribution between the two tissues. Similarly,
      repeat element methylation is not a good surrogate measure of global DNA
      methylation in both blood and colonic mucosa. There was no evidence that mucosal
      global DNA methylation or folate distribution was related to the presence of
      cancer per se, suggesting that if abnormalities exist, they are confined to
      individual cells rather than the entire colon.

PMID- 22609763
TI  - Obesity and ovarian cancer survival: a systematic review and meta-analysis.
AB  - Studies that have examined the association between obesity and ovarian cancer
      survival have provided conflicting results. We reviewed and quantitatively
      summarized existing evidence, exploring potentially important sources of
      variability, such as the timing of body mass index (BMI) assessment and different
      cutpoints used to categorize BMI. A systematic search of MEDLINE and EMBASE was
      conducted to identify original data evaluating the association between obesity
      and survival in women with ovarian cancer. Adjusted hazard ratios (HR) from
      studies were pooled using a random-effects model. The meta-analysis of 14 studies
      showed slightly poorer survival among obese than in non-obese women [pooled HR,
      1.17; 95% confidence interval (CI), 1.03-1.34]. This estimate did not vary
      appreciably when BMI was measured before diagnosis (1.13; 0.95-1.35), at the time
      of diagnosis (1.13; 0.81-1.57) or at the commencement of chemotherapy (1.12; 0.96
      1.31). We found a slightly stronger association in studies that only included
      women with a BMI >= 30 in their "obese" group (1.20) than in studies that also
      included overweight women (BMI >= 25; 1.14). Women with ovarian cancer who are
      obese appear to have slightly worse survival than non-obese women. However, there
      is a large amount of inter-study variation, which means that no solid conclusions
      can be drawn.

PMID- 22609764
TI  - Using video Social StoriesTM to increase task engagement for middle school
      students with autism spectrum disorders.
AB  - Four middle school students with autism spectrum disorders participated in a
      brief functional analysis and a video Social StoriesTM intervention to remediate
      attention-seeking and task-avoidance behaviors. Results indicated that matching
      video Social StoriesTM to specific functions of behaviors increased task
      engagement behaviors in the general education classroom for all students. In
      addition, special and general education teachers, as well as participating
      students, reported favorable social acceptability of the intervention.

PMID- 22609765
TI  - Tributes to Michel Hersen's contribution to the field. The Mississippi years
      (1969-1974).
AB  - The 4 years that Michel Hersen spent at the University of Mississippi Medical
      Center (1970-1974) are described in this article from the viewpoint of his place
      in the history of the development of behavior analysis and therapy. The
      Department of Psychiatry at the University of Mississippi Medical Center became a
      leader in enhancing the role of psychologists as clinician researchers within
      psychiatry and applying basic findings from psychology to the bedside. A vigorous
      research program involving psychology residents and postdoctoral students, and
      psychology and psychiatry faculty emerged from this integration of science and
      practice. Many of the faculty members, including Michel Hersen, became leaders in
      the field of behavior therapy. Much of what was groundbreaking at the time is now
      commonplace within many medical schools.

PMID- 22609766
TI  - Relationship between cognition, magnetic resonance white matter hyperintensities,
      and cardiovascular autonomic changes in late-life depression.
AB  - OBJECTIVES: To explore the relationship between specific aspects of cognition,
      white matter hyperintensities (WMHs), and cardiovascular autonomic parameters in
      late-life depression (LLD). DESIGN: Cross-sectional analysis. SETTING: Secondary
      care psychiatry. PARTICIPANTS: Forty-one individuals older than 60 years, with
      current or previous history of major depression, and 32 age-matched comparison
      subjects. MEASUREMENTS: Cognition was assessed by a standardized computer battery
      of tasks (Cognitive Drug Research) that measured processing speed, attention,
      episodic memory, and working memory. Cardiovascular autonomic parameters were
      estimated by a noninvasive device that calculated blood pressure, heart rate
      variability, and baroreflex sensitivity (Task Force Monitor). Magnetic resonance
      imaging was performed on a 3-T magnetic resonance imaging system, and WMH volume
      was estimated using an automated validated method. RESULTS: As expected,
      cognitive deficits in all tested domains were present in LLD subjects compared
      with comparison subjects. In the LLD group, processing speed was correlated with
      scores on memory and working memory tasks. Attentional deficits were correlated
      with total and periventricular WMH volume, and episodic memory was associated
      with heart rate variability. There were no associations between cognitive
      variables and traditional vascular risk factors or between cognitive variables
      and any of these parameters in the comparison subjects. CONCLUSIONS: This study
      suggests that processing speed may be an important factor underlying deficits in
      LLD, but it also indicates that other factors, including those related to
      vascular disease, are important and thus provide further support for the vascular
      depression hypothesis.

PMID- 22609767
TI  - Cardiac pathological changes of Atlantic salmon (Salmo salar L.) affected with
      heart and skeletal muscle inflammation (HSMI).
AB  - Heart and skeletal muscle inflammation (HSMI) is a disease of marine farmed
      Atlantic salmon where the pathological changes associated with the disease
      involve necrosis and an infiltration of inflammatory cells into different regions
      of the heart and skeletal muscle. The aim of this work was to characterize
      cardiac changes and inflammatory cell types associated with a clinical HSMI
      outbreak in Atlantic salmon using immunohistochemistry. Different immune cells
      and cardiac tissue responses associated with the disease were identified using
      different markers. The spectrum of inflammatory cells associated with the cardiac
      pathology consisted of mainly CD3(+) T lymphocytes, moderate numbers of
      macrophages and eosinophilic granulocytes. Proliferative cell nuclear antigen
      (PCNA) immuno-reaction identified significantly increased nuclear and cytoplasmic
      staining as well as identifying hypertrophic nuclei. Strong immunostaining was
      observed for major histocompatibility complex (MHC) class II in HSMI hearts.
      Although low in number, a few positive cells in diseased hearts were detected
      using the mature myeloid cell line granulocytes/monocytes antibody indicating
      more positive cells in diseased than non-diseased hearts. The recombinant tumor
      necrosis factor-alpha (TNFalpha) antibody identified stained macrophage-like
      cells and endothelial cells around lesions in addition to eosinophilic granular
      cells (EGCs). These findings suggested that the inflammatory response in diseased
      hearts comprised of mostly CD3(+) T lymphocytes and eosinophilic granular cells
      and hearts exhibited high cell turnover where DNA damage/repair might be the case
      (as identified by PCNA, caspase 3 and terminal deoxynucleotidyl transferase nick
      end labeling (TUNEL) reactivity).

PMID- 22609768
TI  - An iodothyronine deiodinase from Chlamys farreri and its induced mRNA expression
      after LPS stimulation.
AB  - Iodothyronine deiodinase is responsible for the deiodination of thyroxine T4 to
      T3, and involved in the complex neuroendocrine-immune regulatory network to
      optimize the immune response in vertebrate. In this study, the full-length cDNA
      of an iodothyronine deiodinase (designated as CfDx) was cloned from scallop
      Chlamys farreri. The complete cDNA sequence of CfDx was of 1404 bp and contained
      an open reading frame of 900 bp encoding a polypeptide of 299 amino acids. The
      deduced amino acid sequence of CfDx contained an in-frame TGA stop codon probably
      encoding an essential selenocysteine (SeC), and there was a conserved region of
      about 15 amino acids surrounding the SeC residue. The CfDx mRNA transcripts were
      detected in all the tested tissues, including haemocytes, hepatopancreas, kidney,
      adductor muscle, gonad, gill and mantle, with the higher expression level in
      hepatopancreas and kidney. After LPS stimulation, the CfDx mRNA expression level
      in haemocytes increased significantly at 12 h (25.35-fold, P < 0.05) and 24 h
      (7.62-fold, P < 0.05), and the concentration of T3 in haemolymph increased
      significantly at 12 h (3.62 ng dL(-1), P < 0.05) even the concentration of T4 did
      not change significantly. After scallop received an injection of 50 MUg CfDx
      dsRNA, the expression level of CfDx mRNA in haemocytes began to decrease
      significantly at 36 h and maintained the relative low level (about 0.3-fold of
      the PBS control group) from 36 to72 h, but the ratio of T4/T3 in haemolymph began
      to increase at 36 h (2.31-fold, P < 0.05) and kept increasing from 36 to 72 h
      comparing with that in the PBS control group. These results indicated that CfDx
      was a homologue of iodothyronine deiodinase in scallop C. farreri, and it might
      be involved in the immunomodulation via regulating the concentration of thyroid
      hormones T3 and T4 in the haemolymph of scallop.

PMID- 22609769
TI  - Chemical recognition and binding kinetics in a functionalized tunnel junction.
AB  - 4(5)-(2-mercaptoethyl)-1H-imidazole-2-carboxamide is a molecule that has multiple
      hydrogen bonding sites and a short flexible linker. When tethered to a pair of
      electrodes, it traps target molecules in a tunnel junction. Surprisingly large
      recognition-tunneling signals are generated for all naturally occurring DNA bases
      A, C, G, T and 5-methyl-cytosine. Tunnel current spikes are stochastic and
      broadly distributed, but characteristic enough so that individual bases can be
      identified as a tunneling probe is scanned over DNA oligomers. Each base yields a
      recognizable burst of signal, the duration of which is controlled entirely by the
      probe speed, down to speeds of 1 nm s -1, implying a maximum off-rate of 3 s -1
      for the recognition complex. The same measurements yield a lower bound on the on
      rate of 1 M -1 s -1. Despite the stochastic nature of the signals, an optimized
      multiparameter fit allows base calling from a single signal peak with an accuracy
      that can exceed 80% when a single type of nucleotide is present in the junction,
      meaning that recognition-tunneling is capable of true single-molecule analysis.
      The accuracy increases to 95% when multiple spikes in a signal cluster are
      analyzed.

PMID- 22609770
TI  - Synthesis and reactivity of 2-azametallacyclobutanes.
AB  - 2-Azametallacyclobutanes have been reported for a number of metals. This
      Perspective provides a brief overview of 2-azametallacyclobutanes, focusing on
      complexes in which the ring nitrogen is anionic (amido).

PMID- 22609771
TI  - Comparison of umbo velocity in air- and bone-conduction.
AB  - This study investigates the ossicular motion produced by bone-conducted (BC)
      sound in live human ears. Laser Doppler vibrometry was used to measure air
      conduction (AC)- and BC-induced umbo velocity (V(U)) in both ears of 10 subjects,
      20 ears total. Sound pressure in the ear canal (P(EC)) was measured
      simultaneously. For air conduction, V(U) at standard hearing threshold level was
      calculated. For BC, DeltaV was defined as the difference between V(U) and the
      tympanic ring velocity (an estimate of the skull velocity measured in the ear
      canal). DeltaV and P(EC) at BC standard hearing threshold were calculated. DeltaV
      at standard BC threshold was significantly smaller than V(U) at standard AC
      threshold between 500 Hz and 2000 Hz. Ear canal pressure at BC threshold tended
      to be smaller than for AC below 3000 Hz (with significant differences at 1000 Hz
      and 2000 Hz). Our results are most consistent with inertia of the ossicles and
      cochlear fluid driving BC hearing below 500 Hz, but with other mechanisms playing
      a significant role at higher frequencies. Sound radiated into the external ear
      canal might contribute to BC hearing at 3000 Hz and above.

PMID- 22609773
TI  - Effects of randomizing phase on the discrimination between amplitude-modulated
      and quasi-frequency-modulated tones.
AB  - This study investigated the bandwidth of phase sensitivity. Subjects
      discriminated amplitude-modulated tones (AM), and quasi-frequency-modulated tones
      (QFM) in a two-interval, forced-choice task. An adaptive threshold procedure was
      used to estimate the modulation depth needed to discriminate the stimuli as a
      function of carrier and modulation frequency. Non-monotonicities in threshold
      bandwidth functions were often observed at higher modulation frequencies. The
      results are discussed in terms of two potential cues: (1) waveform envelope, (2)
      cubic distortion products. In order to degrade the information obtained from
      auditory distortions, the phase for the carrier frequency was randomly sampled
      from a uniform distribution, which diminished the non-monotonicities with minimal
      effect at lower modulation frequencies. Model simulations demonstrated that phase
      randomization degrades distortion product cues with only a modest effect on
      temporal cues. Final results show that maximum bandwidths for phase sensitivity
      (BW(max)) were not proportional to carrier frequencies.

PMID- 22609772
TI  - Does it take older adults longer than younger adults to perceptually segregate a
      speech target from a background masker?
AB  - Older adults often find it more difficult than younger adults to attend to a
      target talker when there are other people talking. One possible reason for this
      difficulty is that it may take them longer to perceptually segregate the target
      speech from competing speech. This study investigated age-related differences in
      the time it takes to segregate target speech from either a speech spectrum noise
      masker or a babble masker (many people talking simultaneously). Specifically, we
      employed five different delays (0.1 s-1.1 s) between masker onset and target
      speech onset. Four signal-to-masker ratios were employed at each delay to
      determine the 50% thresholds for word recognition accuracy when target words were
      masked by either speech spectrum noise or multi-talker babble. Thresholds for
      word recognition decreased exponentially as a function of the masker-word-onset
      delay, at the same rate for younger and older adults, when the masker was speech
      spectrum noise. When the masker was babble, thresholds for younger adults
      decreased exponentially with delay at the same rate as they did when the masker
      was speech spectrum noise. The word recognition thresholds for older adults,
      however, did not appear to change over the range of delays explored in this
      study. In addition, the average difference between word recognition thresholds
      for younger and older adults (younger adult thresholds < older adult thresholds)
      was significantly larger when the masker was babble than when it was noise. These
      results indicate that older adults are as fast as younger adults at separating
      speech from a steady-state noise masker, but are not as capable as younger adults
      of taking advantage of the delayed onset of the speech target when the masker is
      babble. The potential contributions of age-related sensory and cognitive declines
      to these stream segregation effects are discussed. Finally, we conclude that age
      related differences in the timeline for stream segregation contribute to the
      difficulties older adults experience in listening to speech in a background of
      babble.

PMID- 22609774
TI  - A new technique for multiple re-use of planar patch clamp chips.
AB  - The patch clamp technique is widely used for recording the activity of ion
      channels in single cells and lipid bilayers. Most platforms utilize borosilicate
      glass configured as a pipette, however more recently planar patch clamp chips
      have been developed that require less technical expertise. Planar patch clamp
      chips in systems like the Nanion Port-a-Patch are useful in that they allow more
      rapid throughput in drug screening studies. This technique also has the ability
      to perform rapid solution changes from the intracellular side. A current drawback
      with the planar patch clamp chips is the need to utilize a separate chip for each
      experiment. This increases the cost of each experiment and is due to the fact
      that the ~1MUm aperture used for cell attachment is thought to retain cellular
      debris thereby preventing subsequent cell attachment and formation of GOmega
      seals. In the present study we have for the first time solved the technical
      problem of developing a simple protocol for re-use of Nanion planar patch clamp
      chips. The re-use methodology is demonstrated in whole cell patch clamp studies
      of HEK-293 cells expressing the electrogenic sodium bicarbonate cotransporter
      NBCe1-A in protocols involving external and internal solution changes, and CHO-K1
      cells with incorporated gramicidin channels.

PMID- 22609775
TI  - Sirt3 inhibits hepatocellular carcinoma cell growth through reducing Mdm2
      mediated p53 degradation.
AB  - Sirt3 is a member of the mammalian sirtuin family that is localized to
      mitochondria and plays a role in the control of the metabolic activity. Recently,
      Sirt3 has been reported to be associated with the deregulating metabolism of
      cancer cells. However, the role of Sirt3 in hepatocellular carcinoma (HCC) has
      never been studied. In this study, we found that Sirt3 protein expression was
      downregulated in human HCC tissue. We also showed that overexpression of Sirt3
      using adenovirus inhibited HCC cell growth (two cell lines: HepG2 and HuH-7
      cells) and induced apoptosis, which was evidenced by the increase of LDH leakage,
      enhancement of TUNEL-positive cells number and promotion of AIF translocation to
      nuclei. Sirt3 overexpression reduced the intracellular NAD(+) level, repressed
      the ERK1/2 signaling pathway, and activated the Akt and JNK signaling pathways.
      Furthermore, Sirt3 overexpression upregulated p53 protein level through
      downregulating Mdm2 and thereby slowing p53 degradation. Collectively, our data
      suggests that Sirt3 may play an important role in HCC development and progression
      and may be a promising therapeutic target for HCC.

PMID- 22609776
TI  - Effects of short-hairpin RNA-inhibited beta-catenin expression on the growth of
      human multiple myeloma cells in vitro and in vivo.
AB  - Multiple myeloma (MM) is thrombogenic as a consequence of multiple hemostatic
      effects. Overexpression of beta-catenin has been observed in several types of
      malignant tumors, including MM. However, the relationship between beta-catenin
      expression and MM remains unclear. In the present study, RNA interference was
      used to inhibit beta-catenin expression in RPMI8226 cells. RT-PCR and Western
      blotting analyses showed that beta-catenin mRNA and protein expression were
      markedly down-regulated by CTNNB1 shRNA. Western blotting showed that the protein
      levels of cyclin D1 and glutamine synthetase were downregulated and supported the
      transcriptional regulatory function of beta-catenin. The MTT assay showed that
      CTNNB1 shRNA could have significant inhibitory effects on the proliferation of
      RPMI8226 cells. The TOPflash reporter assay demonstrated significant
      downregulation after CTNNB1 shRNA transfection in RPMI8226 cells. Flow cytometric
      analyses also showed significantly profound apoptosis in CTNNB1 shRNA cells. We
      found CTNNB1 silence led to growth inhibition of MM growth in vivo.
      Immunohistochemical analyses showed that c-myc and beta-catenin were reduced in
      CTNNB1 shRNA tumor tissues, but that expression of cleaved caspase-3 was
      increased. These results show that beta-catenin could be a new therapeutic agent
      that targets the biology of MM cells.

PMID- 22609777
TI  - The anti-tumor effect of cross-reacting material 197, an inhibitor of heparin
      binding EGF-like growth factor, in human resistant ovarian cancer.
AB  - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a
      promising target for ovarian cancer therapy. Cross-reacting material 197
      (CRM197), a specific HB-EGF inhibitor, has been proven to represent possible
      chemotherapeutic agent for ovarian cancer. However, the effect of CRM197 on the
      resistant ovarian carcinoma cells has not been sufficiently elucidated. Here, we
      found that HB-EGF was over-expressed in a paclitaxel-resistant human ovarian
      carcinoma cell line (A2780/Taxol) and a cisplatin-resistant cell line
      (A2780/CDDP), as well as the xenograft mouse tissue samples with these cells. To
      investigate the possible significance of the HB-EGF over-expression in
      A2780/Taxol and A2780/CDDP cells, we inhibited HB-EGF expression by CRM197 to
      investigate the effect of CRM197 treatment on these cells. We observed that
      CRM197 significantly induced anti-proliferative activity in a dose-dependent
      manner with the cell-cycle arrest at the G0/G1 phase and enhanced apoptosis in
      A2780/Taxol and A2780/CDDP cells. The sensitive ovarian carcinoma parental cell
      line (A2780), A2780/Taxol and A2780/CDDP cells formed tumors in nude mice, and
      enhanced tumorigenicity was observed in drug-resistant tumors. Furthermore, we
      observed that CRM197 significantly suppressed the growth of drug-resistant
      ovarian cancer xenografts in vivo (p<0.001). These results suggest that CRM197 as
      an HB-EGF-targeted agent has potent anti-tumor activity in paclitaxel- and
      cisplatin-resistant ovarian cancer which over-express HB-EGF.

PMID- 22609778
TI  - Prevention of gamma-radiation induced cellular genotoxicity by tempol: protection
      of hematopoietic system.
AB  - Tempol (TPL) under in vitro conditions reduced the extent of gamma radiation
      induced membrane lipid peroxidation and disappearance of covalently closed
      circular form of plasmid pBR322. TPL protected cellular DNA from radiation
      induced damage in various tissues under ex vivo and in vivo conditions as
      evidenced by comet assay. TPL also prevented radiation induced micronuclei
      formation (in peripheral blood leucocytes) and chromosomal aberrations (in bone
      marrow cells) in whole body irradiated mice. TPL enhanced the rate of repair of
      cellular DNA (blood leucocytes and bone marrow cells) damage when administered
      immediately after radiation exposure as revealed from the increased Cellular DNA
      Repair Index (CRI). The studies thus provided compelling evidence to reveal the
      effectiveness of TPL to protect hematopoietic system from radiation injury.

PMID- 22609779
TI  - Advanced adipose-derived stem cell protein extracts with antioxidant activity
      modulates matrix metalloproteinases in human dermal fibroblasts.
AB  - Advanced adipose-derived stem cell protein extracts (AAPE) were used instead of
      live stem cells to investigate their effect on oxidative stress and matrix
      metalloproteinases (MMPs) related to tissue repair in human dermal fibroblasts
      (HDFs). In this study, it was observed that AAPE at 2MUg/ml specifically
      exhibited scavenging activity of hydrogen peroxide and reducing power. The
      inhibitory effect of AAPE at 2MUg/ml on MMP-2 activity was increased in the
      presence of phorbol myristate acetate (PMA). In the absence of PMA, AAPE
      significantly enhanced activities of MMP-1 and MMP-2 in HDFs, respectively.
      However, the level of MMP-1 expression was decreased in a dose dependent manner
      by AAPE. In addition, while the level of extracellular signal-regulated kinases 1
      (ERK1) activation was reduced in the presence of AAPE compared to blank, the
      level that of ERK2 activation was not changed. The expression level of c-Fos, a
      part of activator protein-1 (AP-1), was increased in nucleus of HDFs. These
      results reveal that activation of MMPs in the presence of AAPE was increased via
      AP-1 in HDFs, suggesting that AAPE can be a potential candidate for tissue
      repair.

PMID- 22609780
TI  - Occurrence and antimicrobial susceptibility of Porphyromonas spp. and
      Fusobacterium spp. in dogs with and without periodontitis.
AB  - The occurrence of Porphyromonas gulae, Porphyromonas macacae, Fusobacterium
      nucleatum and Fusobacterium canifelinum in subgingival plaque from dogs with and
      without periodontitis as well as their antimicrobial susceptibility were
      evaluated. From 50 dogs with periodontitis were identified 38 P. gulae, 8 P.
      macacae, 26 F. nucleatum and 15 F. canifelinum, and from 50 dogs without
      periodontitis were identified 15 P. gulae, 12 F. nucleatum and 11 F. canifelinum.
      All strains were susceptible to most of the antibiotics tested, however,
      different resistance rates to clarithromycin, erythromycin and metronidazole
      among strains were observed. The role of P. gulae, P. macacae, F. nucleatum and
      F. canifelinum in periodontal disease of household pets needs to be defined to a
      better prevention and treatment of the canine periodontitis.

PMID- 22609781
TI  - Modifications on the basic skeletons of vinblastine and vincristine.
AB  - The synthetic investigation of biologically active natural compounds serves two
      main purposes: (i) the total synthesis of alkaloids and their analogues; (ii)
      modification of the structures for producing more selective, more effective, or
      less toxic derivatives. In the chemistry of dimeric Vinca alkaloids enormous
      efforts have been directed towards synthesizing new derivatives of the antitumor
      agents vinblastine and vincristine so as to obtain novel compounds with improved
      therapeutic properties.

PMID- 22609782
TI  - Tropical plant extracts as potential antihyperglycemic agents.
AB  - Preliminary investigations on 14 plant extracts (obtained by ethanolic and
      aqueous extraction) identified those having high antioxidant and a significant
      total phenolic content. Antihyperglycemic, alpha-amylase and alpha-glucosidase
      inhibition activities were also observed. A correlation between the
      antihyperglycemic activity, total phenolic content and antioxidant (DPPH
      scavenging) activity was established. To further substantiate these findings, the
      possibility of tannins binding non-specifically to enzymes and thus contributing
      to the antihyperglycemic activity was also investigated. Our study clearly
      indicated that the antihyperglycemic activity observed in the plant extracts was
      indeed not due to non-specific tannin absorption.

PMID- 22609783
TI  - Scope and limitations of a novel synthesis of 3-arylazonicotinates.
AB  - The reaction of 3-oxo-3-phenyl-2-phenylhydrazonal with functionally substituted
      and heteroaromatic substituted acetonitrile to yield arylazonicotinic acid
      derivatives and 5-arylsubstituted pyridines was established. In some cases the
      produced nicotinates could not be isolated as they underwent thermally induced
      6pi-electrocyclization yielding polynuclear pyridine derivatives.

PMID- 22609784
TI  - The vasorelaxant mechanisms of a Rho kinase inhibitor DL0805 in rat thoracic
      aorta.
AB  - Rho-kinase has been suggested as a potential therapeutic target in the treatment
      of cardiovascular diseases. The Rho-kinase signaling pathway is substantially
      involved in vascular contraction. The aim of the present study was to evaluate
      the vasorelaxant effects of Rho kinase inhibitor DL0805 in isolated rat aortic
      rings and to investigate its possible mechanism(s). It was found that DL0805
      exerted vasorelaxation in a dose-dependent manner in NE or KCl-induced sustained
      contraction and partial loss of the vasorelaxation under endothelium-denuded
      rings. The DL0805-induced vasorelaxation was significantly reduced by the nitric
      oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester, the guanylate
      cyclase inhibitor methylene blue and the cyclooxygenase inhibitor indomethacin.
      The voltage-dependent K+ channel blocker 4-aminopyridine remarkably attenuated
      DL0805-induced relaxations. However, the ATP-sensitive K+ channel blocker
      glibenclamide and Ca2+-activated K+ channel blocker tetraethylammonium did not
      affect the DL0805-induced relaxation. In the endothelium-denuded rings, DL0805
      also reduced NE-induced transient contraction and inhibited contraction induced
      by increasing external calcium. These findings suggested that DL0805 is a novel
      vasorelaxant compound associated with inhibition of Rho/ROCK signaling pathway.
      The NO-cGMP pathway may be involved in the relaxation of DL0805 in endothelium
      intact aorta. The vasorelaxant effect of DL0805 is partially mediated by the
      opening of the voltage-dependent K+ channels.

PMID- 22609785
TI  - Inhibitory effect and mechanism on antiproliferation of isoatriplicolide tiglate
      (PCAC) from Paulownia Coreana.
AB  - Paulownia coreana has traditionally been used as the medicine and health food in
      the treatment of cancer and infectious diseases. In the present study, a new
      antiproliferation agent, isoatriplicolide tiglate (PCAC) was isolated from the
      chloroform soluble fraction of the leaves of Paulownia coreana. The
      antiproliferation activities of PCAC plant extract was examined in breast and
      cervical cancer cell lines in a time-and dose-dependent manners. Our in vitro
      experiments showed that PCAC suppresses the cell growth and proliferation of
      cancer cells at a relatively low concentration (< 10 ug/mL) and induces apoptosis
      at a high concentration (> 50 ug/mL). Western blot analysis showed that
      concentration higher than 50 ug/mL induces a time-dependent increase in the
      percentage of apoptotic cells. In this case, PCAC uses both extrinsic and
      intrinsic pathways for the apoptosis. PCAC treatment decreased the expression of
      pro-caspase 8, 9, and 3, the main regulators of apoptotic cell death, in MDA-MB
      231 cells, accompanied by the activation of caspase 8, 9, and 3. More
      importantly, PCAC inhibited the in vitro proliferation of six other human breast
      and cervical cancer cell lines. In conclusion, our data strongly suggest that
      PCAC acts as an antiproliferation agents particularly against breast and cervical
      cancers by inducing cell cycle arrest in the S/G2 phase and caspase dependent
      apoptosis at relatively low (< 10 MUg/mL) and high (> 50 ug/mL) concentrations,
      respectively.

PMID- 22609786
TI  - Antibacterial evaluation of some Schiff bases derived from 2-acetylpyridine and
      their metal complexes.
AB  - A series of Schiff bases derived from 2-acetylpyridne and their metal complexes
      were characterized by elemental analysis, NMR, FT-IR and UV-Vis spectral studies.
      The complexes were screened for anti-bacterial activity against Methicillin
      resistant Staphylococcus aureus (MRSA), Acinetobacter baumanni (AC), Klebsiella
      pneumonie (KB) and Pseudomonas aeruginosa (PA) using the disc diffusion and micro
      broth dilution assays. Based on the overall results, the complexes showed the
      highest activities against MRSA while a weak antibacterial activity was observed
      against A. baumanii and P. aeruginosa.

PMID- 22609787
TI  - Preparation of curcumin-loaded liposomes and evaluation of their skin permeation
      and pharmacodynamics.
AB  - This study aimed to investigate the in vitro skin permeation and in vivo
      antineoplastic effect of curcumin by using liposomes as the transdermal drug
      delivery system. Soybean phospholipids (SPC), egg yolk phospholipids (EPC), and
      hydrogenated soybean phospholipids (HSPC) were selected for the preparation of
      different kinds of phospholipids composed of curcumin-loaded liposomes: C-SPC-L
      (curcumin-loaded SPC liposomes), C-EPC-L (curcumin-loaded EPC liposomes), and C
      HSPC-L (curcumin-loaded HSPC liposomes). The physical properties of different
      lipsomes were investigated as follows: photon correlation spectroscopy revealed
      that the average particle sizes of the three types of curcumin-loaded liposomes
      were 82.37 +/- 2.19 nm (C-SPC-L), 83.13 +/- 4.89 nm (C-EPC-L), and 92.42 +/- 4.56
      nm (C-HSPC-L), respectively. The encapsulation efficiency values were found to be
      82.32 +/- 3.91%, 81.59 +/- 2.38%, and 80.77 +/- 4.12%, respectively. An in vitro
      skin penetration study indicated that C-SPC-L most significantly promoted drug
      permeation and deposition followed by C-EPC-L, C-HSPC-L, and curcumin solution.
      Moreover, C-SPC-L displayed the greatest ability of all loaded liposomes to
      inhibit the growth of B16BL6 melanoma cells. Therefore, the C-SPC-L were chosen
      for further pharmacodynamic evaluation. A significant effect on antimelanoma
      activity was observed with C-SPC-L, as compared to treatment with curcumin
      solution in vivo. These results suggest that C-SPC-L would be a promising
      transdermal carrier for curcumin in cancer treatment.

PMID- 22609788
TI  - A sandwich HIV p24 amperometric immunosensor based on a direct gold
      electroplating-modified electrode.
AB  - Acquired immune deficiency syndrome (AIDS) is a severe communicable immune
      deficiency disease caused by the human immune deficiency virus (HIV). The
      analysis laboratory diagnosis of HIV infection is a crucial aspect of controlling
      AIDS. The p24 antigen, the HIV-1 capsid protein, is of considerable diagnostic
      interest because it is detectable several days earlier than host-generated HIV
      antibodies following HIV exposure. We present herein a new sandwich HIV p24
      immunosensor based on directly electroplating an electrode surface with gold
      nanoparticles using chronoamperometry, which greatly increased the conductivity
      and reversibility of the electrode. Under optimum conditions, the electrochemical
      signal showed a linear relationship with the concentration of p24, ranging from
      0.01 ng/mL to 100 ng/mL (R > 0.99), and the detection limit was 0.008 ng/mL.
      Compared with ELISA, this method increased the sensitivity by more than two
      orders of magnitude (the sensitivity of ELISA for p24 is about 1 ng/mL). This
      immunosensor may be broadly applied to clinical samples, being distinguished by
      its ease of use, mild reaction conditions, guaranteed reproducibility, and good
      anti-interference ability.

PMID- 22609789
TI  - Metathesis transformations of natural products: cross-metathesis of natural
      rubber and mandarin oil by Ru-alkylidene catalysts.
AB  - This study reports on the degradation of natural rubber (NR) via crossmetathesis
      with mandarin oil and d-limonene, an abundant compound in essential oils; that
      were used as chain transfer agents (CTAs) and green solvents. Reactions were
      performed in the presence of the ruthenium-alkylidene catalysts
      (PCy3)2(Cl)2Ru=CHPh (I) and (1,3-dimesityl-4,5-dihydroimidazol-2-ylidene)
      (PCy3)Cl2Ru=CHPh (II), respectively. Catalyst II bears an N-heterocyclic carbene
      ligand (NHC) bounded to the ruthenium atom, which has a strong basic character;
      therefore it is more active toward trisubstituted olefins in comparison with
      catalyst I. In both cases, isolated monoterpene-terminated isoprene oligomers
      were obtained as products of the cross-metathesis degradation of NR. In the
      presence of catalyst II molecular weight values around M(n) * 102 and yields of
      80% were obtained; whereas with catalyst I, the molecular weights of products
      were about M(n) * 104 with yields ranging 70 to 74%. The composition and yield of
      NR degradation products were determined by GC/MS (EI) analysis and it was found
      that the oligomers obtained have primarily one vinyl group and one terpene
      monocyclic group at the chain end, with isoprene units A(m) = 2, 3 y 4.

PMID- 22609790
TI  - Green and highly efficient synthesis of 2-arylbenzothiazoles using glycerol
      without catalyst at ambient temperature.
AB  - A one-pot and clean synthesis of 2-arylbenzothiazoles via the ambient temperature
      reaction of 2-aminothiophenols and aromatic aldehydes without catalyst in
      glycerol as a green solvent has been reported.

PMID- 22609792
TI  - Self-reported versus professionally assessed functional limitations in community
      dwelling very old individuals.
AB  - The objective of this study was to examine the relationship between self-reported
      and professionally assessed functional limitations in community-dwelling very old
      individuals. In total, 306 single-living adults aged 81-90 years were included in
      this cross-sectional study. The main outcome measure was the presence and absence
      of self-reported and professionally assessed functional limitations. A
      significant correlation was found between the total number of self-reported and
      professionally assessed functional limitations in the total sample (intraclass
      correlation=0.65) as well as in subgroups with respect to sex, age, and
      depression. When item-wise differences in the two assessments were assessed, the
      results showed significant differences for nine of the 15 functional limitations.
      In general, the participants reported more functional limitations as present than
      the professional did. In conclusion, research on self-reported and professionally
      assessed functional limitations contributes toward the understanding of how
      different modes of data collection influence the results. In this study,
      functional limitations were examined on a broad basis, including physical as well
      as cognitive and perceptual limitations. Once the assessments of self-reporting
      have been refined, we will have a more nuanced picture of functional limitations,
      incorporating self-report as well as professional assessments.

PMID- 22609793
TI  - An implanted 8-channel array coil for high-resolution macaque MRI at 3T.
AB  - An 8-channel receive coil array was constructed and implanted adjacent to the
      skull in a male rhesus monkey in order to improve the sensitivity of (functional)
      brain imaging. The permanent implant was part of an acrylic headpost assembly and
      only the coil element loop wires were implanted. The tuning, matching, and
      preamplifier circuitry was connected via a removable external assembly. Signal-to
      noise ratio (SNR) and noise amplification for parallel imaging were compared to
      single-, 4-, and 8-channel external receive-only coils routinely used for macaque
      fMRI. In vivo measurements showed significantly improved SNR within the brain for
      the implanted versus the external coils. Within a region-of-interest covering the
      cerebral cortex, we observed a 5.4-, 3.6-fold, and 3.4-fold increase in SNR
      compared to the external single-, 4-, and 8-channel coils, respectively. In the
      center of the brain, the implanted array maintained a 2.4*, 2.5*, and 2.1* higher
      SNR, respectively compared to the external coils. The array performance was
      evaluated for anatomical, diffusion tensor and functional brain imaging. This
      study suggests that a stable implanted phased-array coil can be used in macaque
      MRI to substantially increase the spatial resolution for anatomical, diffusion
      tensor, and functional imaging.

PMID- 22609794
TI  - In vivo imaging of inhibitory, GABAergic neurons by MRI.
AB  - The unambiguous detection of specific neuronal subtypes is up to now only
      possible with invasive techniques or optical imaging after genetic modification.
      High field magnetic resonance imaging (MRI) has the ability to visualize the
      brain structure and anatomy noninvasively, with high resolution--but missing the
      cell specific and functional information. Here we present a new tool for
      neuroimaging with MRI, enabling the selective detection of GABAergic neurons
      under in vivo conditions. The specific imaging contrast is achieved by a novel
      paramagnetic contrast agent, which responds to the activity of the enzyme
      glutamic acid decarboxylase--expressed solely by inhibitory neurons. The
      relaxivity of the complex is increased upon decarboxylation of two glutamic acid
      moieties, thus allowing increased water access to the inner and outer
      coordination spheres of the paramagnetic ion. The mechanism and specificity of
      activation were proven with tissue lysates and further applied to a
      differentiation protocol for murine embryonic stem cells. The relaxation
      enhancement was studied quantitatively and revealed decreased longitudinal
      relaxation times in the inhibitory neuron samples compared to the naive stem
      cells in vitro and in vivo. Furthermore, this approach offers not only the
      discrimination of inhibitory, GABAergic neurons in the brain but also may expand
      the usefulness of MRI for functional imaging on a cellular level.

PMID- 22609795
TI  - Electrical neuroimaging of memory discrimination based on single-trial
      multisensory learning.
AB  - Multisensory experiences influence subsequent memory performance and brain
      responses. Studies have thus far concentrated on semantically congruent pairings,
      leaving unresolved the influence of stimulus pairing and memory sub-types. Here,
      we paired images with unique, meaningless sounds during a continuous recognition
      task to determine if purely episodic, single-trial multisensory experiences can
      incidentally impact subsequent visual object discrimination. Psychophysics and
      electrical neuroimaging analyses of visual evoked potentials (VEPs) compared
      responses to repeated images either paired or not with a meaningless sound during
      initial encounters. Recognition accuracy was significantly impaired for images
      initially presented as multisensory pairs and could not be explained in terms of
      differential attention or transfer of effects from encoding to retrieval. VEP
      modulations occurred at 100-130 ms and 270-310 ms and stemmed from topographic
      differences indicative of network configuration changes within the brain.
      Distributed source estimations localized the earlier effect to regions of the
      right posterior temporal gyrus (STG) and the later effect to regions of the
      middle temporal gyrus (MTG). Responses in these regions were stronger for images
      previously encountered as multisensory pairs. Only the later effect correlated
      with performance such that greater MTG activity in response to repeated visual
      stimuli was linked with greater performance decrements. The present findings
      suggest that brain networks involved in this discrimination may critically depend
      on whether multisensory events facilitate or impair later visual memory
      performance. More generally, the data support models whereby effects of
      multisensory interactions persist to incidentally affect subsequent behavior as
      well as visual processing during its initial stages.

PMID- 22609796
TI  - Depressive-like behavior in adrenocorticotropic hormone-treated rats blocked by
      memantine.
AB  - Hyperactivity of the hypothalamic pituitary-adrenal (HPA) axis plays a role in
      the pathophysiology of major depressive disorder (MDD). Recent studies suggest
      the role of the glutamatergic system in the pathophysiology of MDD, and N-methyl
      D-aspartate (NMDA) receptor antagonists have shown antidepressant effects in both
      preclinical and clinical studies. However, little is known about the role of
      adrenocorticotropic hormone (ACTH) specifically in the glutamatergic response to
      HPA axis activation. Glutamate is an NMDA receptor agonist, and glycine and D
      serine act as co-agonists. Here, we measured brain concentrations of these amino
      acids in rats given repeated administration of ACTH (100 MUg/rat/day, sc, for 14
      days). Further, we also evaluated behavioral effects of memantine, a non
      competitive NMDA antagonist, on immobility time in the forced swimming test and
      on locomotor activity in ACTH-treated rats. Compared with control rats,
      glutamine, glycine, L-serine, and D-serine levels were increased in the
      hippocampus of ACTH-treated rats; glutamate, glutamine, glycine, L-serine, and D
      serine were increased in the cerebellum; and glutamine and glycine were increased
      in the frontal cortex and striatum, all with statistical significance.
      Remarkably, these increases in agonists and co-agonists might have led to the
      augmentation of NMDA receptor activity. ACTH treatment increased immobility time
      in the forced swimming test and decreased locomotor activity in rats. On the
      contrary, memantine (10 mg/kg, ip) significantly decreased immobility time in the
      forced swimming test and increased locomotor activity in ACTH-treated rats.
      Furthermore, imipramine (15 mg/kg, ip) did not alter immobility time in the
      forced swimming test whereas this drug significantly decreased locomotor activity
      in ACTH-treated rats. These results suggest that depressive-like behaviors by
      chronic ACTH treatment could be blocked by memantine.

PMID- 22609797
TI  - Characterization of cannabinoid-induced relief of neuropathic pain in rat models
      of type 1 and type 2 diabetes.
AB  - Diabetic neuropathy is a frequent complication of diabetes mellitus with a
      tremendous impact on patients' quality of life, and it remains poorly treated.
      Cannabinoids relieve the signs of diabetic neuropathy in different experimental
      models, including streptozotocin- (STZ-) induced type 1 diabetic rodents, and
      they may also relieve neuropathic signs in type 2 diabetic animals. This study
      compares the effect of the non-selective cannabinoid agonist WIN 55,212-2 (WIN)
      in Zucker Diabetic Fatty (ZDF) rats (type 2 diabetes) and in STZ-injected Wistar
      rats (type 1 diabetes). WIN (or its vehicle) was either systemically administered
      at a non-psychoactive dose or locally injected. Selective CB1 and CB2 cannabinoid
      antagonists were used to characterize WIN antineuropathic effects. Both type 1
      and type 2 diabetic rats showed mechanical allodynia but not thermal
      hyperalgesia. WIN alleviated mechanical allodynia in both models of diabetes. In
      STZ-treated rats, both cannabinoid receptors were involved, whereas in ZDF rats,
      WIN effects seemed to mainly involve the activation of CB1 receptors. Higher
      doses of WIN were needed to significantly relieve mechanical allodynia upon
      intraplantar administration in ZDF vs. STZ-injected rats. Cannabinoids, acting on
      systemic and/or peripheral receptors, may serve as a new therapeutic alternative
      for symptom management in painful neuropathy associated with both type 1 and type
      2 diabetes. Additionally, our results highlight the need for appropriate
      selection of diabetic experimental models because the results from studies in STZ
      induced diabetic rodents might not be applicable in all diabetic situations.

PMID- 22609798
TI  - 5-HT7 receptor activation attenuates thermal hyperalgesia in streptozocin-induced
      diabetic mice.
AB  - The role of 5-HT7 receptors in the nociceptive processing received most attention
      during the last few years. The involvement of 5-HT7 receptors in nerve injury
      induced neuropathic pain states have been reported only recently; however, there
      are no reports on its contribution in diabetic neuropathic pain. We therefore
      planned to investigate the effect of 5-HT7 receptor activation on the changes of
      nociceptive threshold in diabetic mice. Diabetes was induced by a single
      intraperitoneal injection of streptozocin (150 mg/kg, i.p.). The nociceptive
      responses in normal and diabetic animals were tested in the hot-plate and tail
      flick assays. Both hot-plate and tail-flick latencies significantly shortened at
      1-3/4 weeks (thermal hyperalgesia) and prolonged at 6-7 weeks (thermal
      hypoalgesia) after streptozocin administration. At the dose of 10 mg/kg, systemic
      injections of AS-19, a selective 5-HT7 receptor agonist, reduced thermal
      hyperalgesia at early stage of diabetes, but did not influence thermal
      hypoalgesia at late stage. Co-administration of SB-258719, a selective 5-HT7
      receptor antagonist, at a dose that had no effect on its own (10 mg/kg), reversed
      the anti-hyperalgesic effect of AS-19. Our results indicate that systemic
      administration of 5-HT7 receptor agonists may have clinical utility in treating
      diabetic neuropathic pain.

PMID- 22609799
TI  - Human papillomavirus type 16 E6 protein inhibits DNA fragmentation via
      interaction with DNA fragmentation factor 40.
AB  - The E6 oncoprotein of human papillomavirus (HPV) is critical in cervical cancer
      development. Using the yeast two-hybrid assay, we showed that HPV-16 E6 (16E6)
      interacts with one of the DNA fragmentation factors (DFFs), DFF40, which mediates
      DNA degradation during apoptosis. Furthermore, 16E6 interacts with DFF40 through
      its zinc finger motif 2 and a bridge section linking the two zinc finger motifs.
      DNA fragmentation assays disclosed that 16E6 binding to DFF40 leads to blockage
      of DNA cleavage. Our data collectively suggest that suppression of DNA
      fragmentation through 16E6-DFF40 interaction is a central event promoting
      tumorigenesis.

PMID- 22609800
TI  - Proline oxidase promotes tumor cell survival in hypoxic tumor microenvironments.
AB  - Proline is a readily released stress substrate that can be metabolized by proline
      oxidase (POX) to generate either reactive oxygen species (ROS) to induce
      apoptosis or autophagy or ATP during times of nutrient stress. However, the
      contribution of proline metabolism to tumorigenesis in hypoxic microenvironments
      has not been explored. In this study, we investigated the different functions of
      POX under hypoxia and glucose depletion. We found that hypoxia induced POX
      expression in cancer cells in vitro and that POX upregulation colocalized with
      hypoxic tissues in vivo. In addition, the combination of hypoxia and low glucose
      showed additive effects on POX expression. Similar to conditions of low glucose,
      hypoxia-mediated POX induction was dependent on AMP-activated protein kinase
      activation but was independent of HIF-1alpha and HIF-2alpha. Under low-glucose
      and combined low-glucose and hypoxic conditions, proline catabolized by POX was
      used preferentially for ATP production, whereas under hypoxia, POX mediated
      autophagic signaling for survival by generating ROS. Although the specific
      mechanism was different for hypoxia and glucose deprivation, POX consistently
      contributed to tumor cell survival under these conditions. Together, our findings
      offer new insights into the metabolic reprogramming of tumor cells present within
      a hostile microenvironment and suggest that proline metabolism is a potential
      target for cancer therapeutics.

PMID- 22609801
TI  - Expression profiling of Epstein-Barr virus-encoded microRNAs from paraffin
      embedded formalin-fixed primary Epstein-Barr virus-positive B-cell lymphoma
      samples.
AB  - Epstein-Barr virus (EBV) is implicated in a range of B-cell malignancies and
      expresses unique microRNAs (EBV-miRNAs). Due to the requirements for high-quality
      RNA, studies profiling EBV-miRNA in EBV-positive lymphomas have been restricted
      to cell-lines or frozen samples. However, the most commonly available archived
      patient material is paraffin-embedded formalin-fixed (FFPE) tissue. This has
      impeded the widespread profiling of EBV-miRNA expression in clinical samples. The
      requirements for accurate EBV-miRNA real-time RT-PCR quantitation in FFPE tissues
      representing a broad-spectrum of EBV-positive lymphomas were determined
      systematically, including where the neoplastic cells are sparse relative to the
      non-malignant infiltrate. The level of cellular EBV-load correlated strongly with
      the sum of EBV-miRNA expression and the number of EBV-miRNAs detectable. As
      calibrators for cellular EBV-load, the sum EBV-miRNA was optimal to EBV-genome
      copy number and EBER2 expression level, with the added advantage of not requiring
      additional assays. EBV-miRNA was profiled reliably within archival FFPE tissue in
      14/23 patients, but not in tissues with low abundance EBV. This method enabled
      specific and simultaneous detection of numerous EBV-miRNAs in FFPE lymphoma
      samples that contain EBV at high to medium levels, making it as a useful tool for
      studies of EBV-miRNA in the majority of diagnostic biopsies.

PMID- 22609802
TI  - Evaluation of two different swab transport systems in the detection of avian
      influenza virus excretion from infected Pekin ducks (Anas platyrhynchos).
AB  - The role of wild birds in the epidemiology and ecology of influenza A viruses has
      long been recognised (Alexander, 2007a). As a result of the emergence of a H5N1
      highly pathogenic avian influenza (HPAI) virus and the apparent role of wild
      birds in its spread across Asia, Europe and Africa, avian influenza (AI) wild
      bird surveillance has been implemented in many countries including, since
      February 2006, a mandatory programme in the European Union (CEC, 2006a). In the
      present study the detection of virus excreted from Pekin ducks (Anas
      platyrhynchos) infected experimentally with A/mallard/England/2126/07 (H3N6) was
      investigated over a fourteen day period post-infection using cloacal and
      oropharyngeal swabs, with (wet) and without (dry) viral transport medium which
      were collected from each duck in alternating order. For influenza A virus matrix
      gene RNA detection, wet oropharyngeal swabs were significantly more sensitive
      than dry oropharyngeal on days 4-5 after infection. For cloacal samples, dry
      swabs were equivalent or superior to wet swabs throughout the study. Although
      differences in detection between dry and wet swabs were observed, the qualitative
      bird-level results were unaffected, meaning that the infection status of
      individual birds was correctly determined.

PMID- 22609803
TI  - Enhanced photoelectrochemical water-splitting effect with a bent ZnO nanorod
      photo anode decorated with Ag nanoparticles.
AB  - Zinc oxide (ZnO) nanorods coated with silver (Ag) film on a polyethylene
      terephthalate (PET)flexible substrate were used as the photo anode for water
      splitting. The hybrid nanostructures were prepared via low-temperature
      hydrothermal growth and electron beam evaporation. The effects of plasmonic
      enhanced absorption, surface recombination inhibition and improved charge
      transport are investigated by varying the Ag thickness. Light trapping and
      absorption enhancement are further studied by optimizing the curvature of the PET
      substrates. The maximum short circuit current density (JSC, 0.616 mA cm -2) and
      the photoelectron conversion efficiency (PCE, 0.81%) are achieved with an
      optimized Ag film thickness of 10 nm and substrate bending radius of 6.0 mm. The
      maximum JSC and PCE are seven times and ten times, respectively, higher than
      those of the bare ZnO nanorods on flexible substrates without bending. The
      overall PEC performance improvement is attributed to the plasmonic effects
      induced by Ag film and improved charge transport due to inhibition of ZnO surface
      charge recombination. Enhanced light trapping (harvesting) induced by bending the
      PET substrates further improved the overall efficiency.

PMID- 22609804
TI  - Inorganic phosphorus fractionation and its translocation dynamics in a low-P
      soil.
AB  - The translocation of different inorganic phosphorus (Pi) forms in a low-P soil
      (Langfang experimental station, Hebei province, China) over time was investigated
      using P fractionation extraction and a (32)P tracer technique. The L-value and P
      availability of the soil was assessed using 5 different maize genotype (Zea mays
      L.) cultivars. The results showed that the different Pi fractions in the soil
      increased in the order of H(2)SO(4)-extractable P (Ca(10)-P) > Na(3)C(6)H(5)O(7)
      Na(2)S(2)O(4)-extractable P (O-P) > NH(4)Ac-extractable P (Ca(8)-P) > NaHCO(3)
      extractable P (Ca(2)-P), NH(4)F-extractable P (Al-P), NaOH-Na(2)CO(3)-extractable
      P (Fe-P), and the content of plant-unavailable P (Ca(10)-P + O-P) was high, up to
      79.1%, which might be an important reason for P deficiency in this low-P soil.
      The (32)P tracer results showed that after the addition of (32)P-Pi to the soil
      with no P fertilizer applied for 25 d, 29.0% of (32)P was quickly transformed
      into Ca(2)-P (rapidly available P), and 66.1% of (32)P was transformed into Al-P,
      Fe-P and Ca(8)-P (slowly available P). Only 5.0% of (32)P was transformed into O
      P and Ca(10)-P (plant-unavailable P). Moreover, in the soil with P fertilizer
      applied, (32)P transformation into Ca(2)-P increased, and the transformation into
      Ca(8)-P + Fe-P + AL-P and O-P, Ca(10)-P significantly decreased compared to the
      soil with no P fertilizer applied (p < 0.05). This result suggested a higher rate
      for water-soluble P transformation to slowly available and plant-unavailable P in
      P deficient soil than in soil with sufficient P. The results of maize L-value
      determination showed that different genotype maize cultivars had different soil P
      use efficiency and low-P tolerance mechanisms. Low-P tolerant cultivar DSY-32
      regulated soil P-use efficiency and plant P content according to exogenous P
      fertilizer application. However, another low-P tolerant cultivar, DSY-2, used
      soil P more efficiently, regardless of the application of exogenous P.

PMID- 22609805
TI  - Navigating change: second-generation challenges of small-scale fisheries co
      management in the Philippines and Vietnam.
AB  - Early efforts to apply the concept of fisheries co-management in Southeast Asia
      focused primarily on building the effectiveness of local management institutions
      and advocating the merits of the approach so that it would be applied in new
      sites, while gradually learning and adapting to a range of obstacles in practice.
      Today, with co-management widely embraced by the research community and adopted
      as policy by an increasing number of governments, a second-generation perspective
      has emerged. This perspective is distinguished by efforts to navigate and
      influence change in the broader institutional and governance context: (a) a more
      sophisticated appreciation of politics, power relations, and the role of the
      state, (b) efforts to manage resource competition beyond the fisheries sector,
      (c) building institutions for adaptation and learning, and (d) recognizing
      divergent values and goals influencing fisheries management. This paper traces
      the evolution of this second-generation perspective, noting how it has built on
      learning from early practice and how it has been cross-fertilized by theoretical
      innovations in related fields, notably resilience thinking and political ecology.
      We illustrate this evolution through analysis of experience in the Philippines,
      with a relatively long experience of learning and adaptation in fisheries co
      management practice, and Vietnam, where fisheries co-management policies have
      been embraced more recently. Characterizing the second-generation perspective
      helps identify points of convergence in the research and policy community about
      what needs attention, providing a basis for more systematic cross-country and
      cross-regional learning.

PMID- 22609806
TI  - A chain-retrieval model for voluntary task switching.
AB  - To account for the findings obtained in voluntary task switching, this article
      describes and tests the chain-retrieval model. This model postulates that
      voluntary task selection involves retrieval of task information from long-term
      memory, which is then used to guide task selection and task execution. The model
      assumes that the retrieved information consists of acquired sequences (or chains)
      of tasks, that selection may be biased towards chains containing more task
      repetitions and that bottom-up triggered repetitions may overrule the intended
      task. To test this model, four experiments are reported. In Studies 1 and 2,
      sequences of task choices and the corresponding transition sequences (task
      repetitions or switches) were analyzed with the help of dependency statistics.
      The free parameters of the chain-retrieval model were estimated on the observed
      task sequences and these estimates were used to predict autocorrelations of tasks
      and transitions. In Studies 3 and 4, sequences of hand choices and their
      transitions were analyzed similarly. In all studies, the chain-retrieval model
      yielded better fits and predictions than statistical models of event choice. In
      applications to voluntary task switching (Studies 1 and 2), all three parameters
      of the model were needed to account for the data. When no task switching was
      required (Studies 3 and 4), the chain-retrieval model could account for the data
      with one or two parameters clamped to a neutral value. Implications for our
      understanding of voluntary task selection and broader theoretical implications
      are discussed.

PMID- 22609807
TI  - Antiulcerogenic activity of hydroalcoholic fruit extract of Pithecellobium dulce
      in different experimental ulcer models in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The ethnopharmacological importance of
      Pithecellobium dulce is evidenced by its traditional use for gastric
      complications. The aim of the study is to evaluate the gastroprotective activity
      and the mechanism of action of hydroalcoholic fruit extract of P. dulce (HAEPD)
      in rats by using chemical and stress induced ulcer models. MATERIALS AND METHODS:
      Gastric ulcer was induced by administering alcohol (or) acetylsalicylic acid (or)
      hypothermic restraint stress to rats pretreated with HAEPD (200 mg/kgbwt for 30
      day). Volume of gastric fluid, pH, acidity, activities of pepsin, H(+), K(+)
      ATPase, myeloperoxidase, mucin content, nucleic acids, glycoproteins and
      prostaglandin E(2) (PGE(2)) levels were assessed in gastric tissues. RESULTS:
      Ulcer score was significantly minimized in HAEPD administered animals. pH and
      acidity of gastric fluid were significantly minimized and the mucin, PGE(2)
      levels were significantly maintained in drug pre administered animals. The
      activities of H(+), K(+)- ATPase and myeloperoxidase were found to be
      significantly elevated in ulcer control animals and found to be decreased in drug
      pretreated animals. The cell proliferation was found to be enhanced in drug
      received animals. The total protein bound carbohydrate to total protein ratio was
      found to be significantly maintained by HAEPD. The effects were found to be
      comparable with that of standard drug omeprazole. CONCLUSION: It is concluded
      that HAEPD possess a potent antiulcer activity probably by acting as
      cytoprotective and antiacid secretory agent.

PMID- 22609808
TI  - Anti-tumor activity of Annona squamosa seeds extract containing annonaceous
      acetogenin compounds.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Seeds of Annona squamosa L. have been used in the
      south of China as a folk remedy to treat "malignant sores" (cancer). AIM OF THE
      STUDY: To investigate the chemical constituents and the anti-tumor activity of
      the standardized A. squamosa seeds extract in vitro and in vivo. MATERIALS AND
      METHODS: Annonaceous acetogenin profiles of the standardized extract were
      determined by using Fourier transform infrared (FT-IR) and high performance
      liquid chromatography (HPLC) techniques. The anti-tumor activity of the extract
      was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)
      cytotoxicity in vitro and H(22) hepatoma cells transplantation tumor model in
      vivo. RESULTS: The FT-IR spectroscopy showed the presence of annonaceous
      acetogenin compounds in the extract. Two major annonaceous acetogenins: 12, 15
      cis-squamostatin-A and bullatacin were identified and quantified by HPLC. The
      seed extract showed significant anti-tumor activity against four human tumor cell
      lines, especially for MCF-7 (IC(50). 0.25 MUg/ml) and Hep G2 (IC(50). 0.36
      MUg/ml) cells in vitro. The extract inhibited the growth of H(22) tumor cells in
      mice with a maximum inhibitory rate of 69.55% by oral administration. CONCLUSION:
      A. squamosa seed extract showed significant anti-tumor activities against human
      hepatoma cells in vitro and in vivo, indicating a potential for developing the
      extract as a novel anti-liver cancer drug.

PMID- 22609809
TI  - Antinociceptive activity of aqueous extract and isolated compounds of Lithrea
      molleoides.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Lithrea molleoides (Vell.) Engl. (Anacardiaceae)
      is a medicinal plant commonly used in traditional medicine in South America. AIM
      OF THE STUDY: In the present study, the in vivo antinociceptive effect of L.
      molleoides' aqueous extract and its isolated compounds has been investigated.
      MATERIALS AND METHODS: Antinociceptive activity was evaluated through writhing,
      formalin and hot plate tests in mice. The phytochemical analysis was performed.
      RESULTS: The extract produced significant inhibition on nociception induced by
      acetic acid (ED50: 8.7 mg/kg, i.p.) and formalin (ED50: 7.7 mg/kg, i.p.)
      administered intraperitoneally and also orally. Yohimbine diminished the activity
      of the extract in the acetic acid test meanwhile haloperidol enhanced its effect.
      Two majority compounds, shikimic and vanillic acid were active in chemical
      nociceptive models used in this work, producing the highest inhibition of the
      writhing response at a dose of 30 mg/kg i.p. (55.4% and 57.1%, respectively)
      meanwhile at 100 mg/kg p.o. produced a slight response (23.3% and 23.9%,
      respectively). CONCLUSIONS: These results suggest that L. molleoides' aqueous
      extract produced antinociception possibly related to the presence of shikimic and
      vanillic acid. The adrenergic and dopaminergic systems seem to be involved in the
      mechanism of antinociception of the extract.

PMID- 22609811
TI  - Chronic obstructive uropathy due to uretero-inguinal hernia: A case report.
AB  - INTRODUCTION: Inguinal hernia in men is common but uretero-inguinal hernia is
      very rare. PRESENTATION OF CASE: A 85-year-old obese man presented with chronic
      obstructive uropathy with previous renal ultrasound showing bilateral enlarged
      kidneys and hydronephrosis. The medical history revealed a 3-year history of a
      noticeable bilateral partial reducible inguinoscrotal herniae associated with
      urinary symptoms. Progress CT scan showed very large inguinal herniae, which were
      predominantly fat-containing with the ureters herniated, and both kidneys were
      displaced inferiorly. DISCUSSION: Uretero-inguinal hernia in patients with native
      kidneys is rare, but cases of renal failure secondary to uretero-inguinal hernia
      have also been reported previously in the literature with two anatomical
      variations have been reported - paraperitoneal and extraperitoneal types.
      Endourological and surgical procedures are rarely straight-forward because of
      tortuosity of the herniated ureter. CONCLUSION: Although uretero-inguinal hernia
      is rare, it can be the cause of chronic renal impairment.

PMID- 22609810
TI  - Systematic analysis of embryonic stem cell differentiation in hydrodynamic
      environments with controlled embryoid body size.
AB  - The sensitivity of stem cells to environmental perturbations has prompted many
      studies which aim to characterize the influence of mechanical factors on stem
      cell morphogenesis and differentiation. Hydrodynamic cultures, often employed for
      large scale bioprocessing applications, impart complex fluid shear and transport
      profiles, and influence cell fate as a result of changes in media mixing
      conditions. However, previous studies of hydrodynamic cultures have been limited
      in their ability to distinguish confounding factors that may affect
      differentiation, including modulation of embryoid body size in response to
      changes in the hydrodynamic environment. In this study, we demonstrate the
      ability to control and maintain embryoid body (EB) size using a combination of
      forced aggregation formation and rotary orbital suspension culture, in order to
      assess the impact of hydrodynamic cultures on ESC differentiation, independent of
      EB size. Size-controlled EBs maintained at different rotary orbital speeds
      exhibited similar morphological features and gene expression profiles, consistent
      with ESC differentiation. The similar differentiation of ESCs across a range of
      hydrodynamic conditions suggests that controlling EB formation and resultant size
      may be important for scalable bioprocessing applications, in order to standardize
      EB morphogenesis. However, perturbations in the hydrodynamic environment also led
      to subtle changes in differentiation toward certain lineages, including temporal
      modulation of gene expression, as well changes in the relative efficiencies of
      differentiated phenotypes, thereby highlighting important tissue engineering
      principles that should be considered for implementation in bioreactor design, as
      well as for directed ESC differentiation.

PMID- 22609813
TI  - The biology of human breast epithelial progenitors.
AB  - Current evidence suggests that similar to other tissues in the human body mammary
      epithelia cells are being maintained by the unique properties of stem cells,
      undifferentiated as well as lineage-restricted progenitors. Because of their
      longevity, proliferation and differentiation potentials these primitive breast
      epithelial cells are likely targets of transforming mutations that can cause them
      to act as cancer initiating cells. In this context, understanding the molecular
      mechanisms that regulate the normal functions of the human breast epithelial stem
      cells and progenitors and how alterations to these same mechanisms can confer a
      cancer stem cell phenotype on these rare cell populations is crucial to the
      development of new and more effective therapies again breast cancer. This review
      article will examine the current state of knowledge about the isolation and
      characterization of human breast epithelial progenitors and their relevance to
      breast cancer research.

PMID- 22609815
TI  - Sedative load among community-dwelling older individuals:  change over time and
      association with mortality.
AB  - The aim of this study was to investigate the change in sedative load over time
      and the corresponding risk of death among community-dwelling older individuals. A
      random sample of 1000 individuals aged at least 75 years was invited to
      participate in 2004, of whom 700 were community dwelling. Demographic,
      diagnostic, and drug use data were obtained during annual nurse interviews.
      Sedative load was calculated according to a previously published model. The
      prevalence of sedative use increased from 29.3 to 36.1% from 2004 to 2007. In
      unadjusted analyses, sedative load was associated with an increased risk of
      death. After adjusting for clinically important covariates, sedative load was not
      associated with an increased risk of death [sedative load 1-2; hazard ratio 1.12
      (95% confidence interval 0.76-1.64), sedative load of at least 3; hazard ratio
      0.92 (95% confidence interval 0.55-1.56)]. In conclusion, sedative use increased
      during the follow-up but was not associated with an increased risk of death.

PMID- 22609812
TI  - Structures of YAP protein domains reveal promising targets for development of new
      cancer drugs.
AB  - YAP (Yes-associated protein) is a potent oncogene and a major effector of the
      mammalian Hippo tumor suppressor pathway. In this review, our emphasis is on the
      structural basis of how YAP recognizes its various cellular partners. In
      particular, we discuss the role of LATS kinase and AMOTL1 junction protein, two
      key cellular partners of YAP that bind to its WW domain, in mediating cytoplasmic
      localization of YAP and thereby playing a key role in the regulation of its
      transcriptional activity. Importantly, the crystal structure of an amino-terminal
      domain of YAP in complex with the carboxy-terminal domain of TEAD transcription
      factor was only recently solved at atomic resolution, while the structure of WW
      domain of YAP in complex with a peptide containing the PPxY motif has been
      available for more than a decade. We discuss how such structural information may
      be exploited for the rational development of novel anti-cancer therapeutics
      harboring greater efficacy coupled with low toxicity. We also embark on a brief
      discussion of how recent in silico studies led to identification of the cardiac
      glycoside digitoxin as a potential modulator of WW domain-ligand interactions.
      Conversely, dobutamine was identified in a screen of known drugs as a compound
      that promotes cytoplasmic localization of YAP, thereby resulting in growth
      suppressing activity. Finally, we discuss how a recent study on the dynamics of
      WW domain folding on a biologically critical time scale may provide a tool to
      generate repertoires of WW domain variants for regulation of the Hippo pathway
      toward desired, non-oncogenic outputs.

PMID- 22609816
TI  - Sertindole in the long-term treatment of schizophrenia.
AB  - This study assessed the safety and tolerability of sertindole in the long-term
      treatment of schizophrenia. An open-label, noncomparative, flexible-dose study
      was carried out in 11 European countries. Upon completion of an 8-week,
      haloperidol-referenced randomized clinical trial with sertindole, patients were
      offered sertindole maintenance treatment up to 18 months. In total, 294 patients
      were enrolled, of whom 237 (81%) had received sertindole and 57 (19%) had
      received haloperidol in the lead-in trial. The modal dose during the maintenance
      period was 16 mg/day. Patients showed therapeutic improvement indicated by
      significant decreases in the Positive And Negative Syndrome Scale and Clinical
      Global Impression 'severity-of-illness' scores. An adverse event was the primary
      reason for withdrawal in 13% of patients. The most common adverse events were
      fatigue and weight gain, both with incidences of 14%. The incidence of
      extrapyramidal symptoms was 18%, and 11% of the patients required anticholinergic
      medication. No statistically significant changes were observed in laboratory
      values or vital signs, but the mean serum prolactin levels decreased. The mean
      change in weight from baseline to the last assessment was 2.7 kg. The largest
      weight increase was observed in patients who were underweight at baseline. Long
      term treatment with sertindole was safe and well tolerated, and patients showed
      clinical improvement beyond acute treatment.

PMID- 22609817
TI  - Degeneration of axons in spinal white matter in G93A mSOD1 mouse characterized by
      NFL and alpha-internexin immunoreactivity.
AB  - Axonal degeneration is a prominent feature of amyotrophic lateral sclerosis (ALS)
      both in lower motor nerves as well as descending white matter axons in the spinal
      cord of human patients. Although the pathology of lower motor axonal degeneration
      has been described in both human ALS and related transgenic animal models, few
      studies have examined the pathological features of descending axon degeneration,
      particularly in mouse models of ALS. We have examined the degeneration of white
      matter tracts in the G93A mutant superoxide dismutase-1 (mSOD1+) mouse spinal
      cord white matter from 12 weeks of age to end-stage disease. In a G93A mSOD1
      mouse model where green fluorescent protein was expressed in neurons
      (mSOD1+/GFP+), degeneration of white matter tracts was present from the ventral
      to dorsolateral funiculi. This pattern of axonal pathology occurred from 16 weeks
      of age. However, the dorsal funiculus, the site of the major corticospinal tract
      in mice, showed relatively less degeneration. Immunohistochemical analysis
      demonstrated that the neurofilament light chain (NFL) and neuronal intermediate
      filament protein alpha-internexin accumulated in axon swellings in the spinal
      white matter. Increased levels of alpha-internexin protein, in mSOD1+ mouse
      spinal cord tissue, were demonstrated by Western blotting. In contrast,
      degenerating axons did not show obvious accumulations of neurofilament medium and
      heavy chain proteins (NFM and NFH). These data suggest that white matter
      degeneration in this mouse model of ALS is widespread and involves a specific
      molecular signature, particularly the accumulation of NFL and alpha-internexin
      proteins.

PMID- 22609819
TI  - Pharmacological prophylaxis of venous thromboembolism during acute phase of
      spontaneous intracerebral hemorrhage: what do we know about risks and benefits?
AB  - Spontaneous intracerebral hemorrhage (sICH) represents a devastating clinical
      event with high mortality and morbidity rates. Only few patients with sICH are
      treated with neurosurgical evacuation of the hematoma, and the majority of them
      need only a good conservative medical approach. The goal of medical treatment is
      to avoid secondary neurological and systemic complications. Venous
      thromboembolism (VTE) represents one of the most feared complications of sICH,
      and it is a potential cause of death. The balance between the benefit of VTE
      prevention and the risk of hematoma enlargement and/or rebleeding with the use of
      pharmacologic thromboprophylaxis remains controversial because of the lack of
      consistent evidences in the literature. The efficacy of mechanical prophylaxis is
      also uncertain. Consequently, until now there are no clear guidelines and
      scientific evidences available for physicians in this field. The aim of this
      review is to analyze the available literature and guidelines about
      pharmacological VTE prophylaxis in patients with nonsurgical sICH.

PMID- 22609818
TI  - Genetic polymorphisms of HO-1 and COX-1 are associated with aspirin resistance
      defined by light transmittance aggregation in Chinese Han patients.
AB  - BACKGROUND: Cyclooxygenase 1 (COX-1), COX-2, and HO-1 are involved in the process
      of aspirin's effect. The genetic susceptibility of these enzymes to aspirin
      resistance (AR) is unclear. METHODS: A total of 431 patients took aspirin. Using
      arachidonic acid-induced light transmittance aggregation combined with adenosine
      diphosphate-induced light transmittance aggregation, 36 participants served for
      AR, 164 participants for semi-AR, and 231 participants for aspirin sensitivity
      (AS). The AR with 9 single-nucleotide polymorphism in COX-1, COX-2, and HO-1
      genes was investigated. RESULTS: COX-1 rs1330344 (-1676A>G) is associated with
      AR. G-Allele carriers significantly increased the risk of AR. For patients with
      AS as control, P is .02 (odds ratio [OR] = 1.77, confidence interval [CI]: 1.07
      2.92). For patients with semi-AR as control, P is .05. HO-1 rs2071746 (-413A>T)
      is associated with AR. T-Allele carriers significantly increased the risk of AR.
      For patients with AS as control, P is .04 (OR = 1.70, CI: 1.02-2.79). For
      patients with semi-AR as control, P is .05 (OR = 1.68, CI: 1.00-2.80).
      CONCLUSION: rs2071746 in HO-1 gene, rs1330344 in COX-1 gene contribute to AR.

PMID- 22609820
TI  - Chronic stress induces ageing-associated degeneration in rat Leydig cells.
AB  - Several studies have suggested that stress and ageing exert inhibitory effects on
      rat Leydig cells. In a pattern similar to the normal process of Leydig cell
      ageing, stress-mediated increases in glucocorticoid levels inhibit steroidogenic
      enzyme expression that then results in decreased testosterone secretion. We
      hypothesized that chronic stress accelerates the degenerative changes associated
      with ageing in Leydig cells. To test this hypothesis, we established a model of
      chronic stress to evaluate stress-induced morphological and functional
      alterations in Brown Norway rat Leydig cells; additionally, intracellular
      lipofuscin levels, reactive oxygen species (ROS) levels and DNA damage were
      assessed. The results showed that chronic stress accelerated ageing-related
      changes: ultrastructural alterations associated with ageing, cellular lipofuscin
      accumulation, increased ROS levels and more extensive DNA damage were observed.
      Additionally, testosterone levels were decreased. This study sheds new light on
      the idea that chronic stress contributes to the degenerative changes associated
      with ageing in rat Leydig cells in vivo.

PMID- 22609822
TI  - A molecular phylogeny for the Tribe Dacini (Diptera: Tephritidae): systematic and
      biogeographic implications.
AB  - With well over 700 species, the Tribe Dacini is one of the most species-rich
      clades within the dipteran family Tephritidae, the true fruit flies. Nearly all
      Dacini belong to one of two very large genera, Dacus Fabricius and Bactrocera
      Macquart. The distribution of the genera overlap in or around the Indian
      subcontinent, but the greatest diversity of Dacus is in Africa and the greatest
      diversity of Bactrocera is in south-east Asia and the Pacific. The monophyly of
      these two genera has not been rigorously established, with previous phylogenies
      only including a small number of species and always heavily biased to one genus
      over the other. Moreover, the subgeneric taxonomy within both genera is complex
      and the monophyly of many subgenera has not been explicitly tested. Previous
      hypotheses about the biogeography of the Dacini based on morphological reviews
      and current distributions of taxa have invoked an out-of-India hypothesis;
      however this has not been tested in a phylogenetic framework. We attempted to
      resolve these issues with a dated, molecular phylogeny of 125 Dacini species
      generated using 16S, COI, COII and white eye genes. The phylogeny shows that
      Bactrocera is not monophyletic, but rather consists of two major clades:
      Bactrocera s.s. and the 'Zeugodacus group of subgenera' (a recognised, but
      informal taxonomic grouping of 15 Bactrocera subgenera). This 'Zeugodacus' clade
      is the sister group to Dacus, not Bactrocera and, based on current distributions,
      split from Dacus before that genus moved into Africa. We recommend that taxonomic
      consideration be given to raising Zeugodacus to genus level. Supportive of
      predictions following from the out-of-India hypothesis, the first common ancestor
      of the Dacini arose in the mid-Cretaceous approximately 80mya. Major divergence
      events occurred during the Indian rafting period and diversification of
      Bactrocera apparently did not begin until after India docked with Eurasia (50
      35mya). In contrast, diversification in Dacus, at approximately 65mya, apparently
      began much earlier than predicted by the out-of-India hypothesis, suggesting
      that, if the Dacini arose on the Indian plate, then ancestral Dacus may have left
      the plate in the mid to late Cretaceous via the well documented India-Madagascar
      Africa migration route. We conclude that the phylogeny does not disprove the
      predictions of an out-of-India hypothesis for the Dacini, although modification
      of the original hypothesis is required.

PMID- 22609821
TI  - Reduced prostate branching morphogenesis in stromal fibroblast, but not in
      epithelial, estrogen receptor alpha knockout mice.
AB  - Early studies suggested that estrogen receptor alpha (ERalpha) is involved in
      estrogen-mediated imprinting effects in prostate development. We recently
      reported a more complete ERalpha knockout (KO) mouse model via mating beta-actin
      Cre transgenic mice with floxed ERalpha mice. These ACTB-ERalphaKO male mice
      showed defects in prostatic branching morphogenesis, which demonstrates that
      ERalpha is necessary to maintain proliferative events in the prostate. However,
      within which prostate cell type ERalpha exerts those important functions remains
      to be elucidated. To address this, we have bred floxed ERalpha mice with either
      fibroblast-specific protein (FSP)-Cre or probasin-Cre transgenic mice to generate
      a mouse model that has deleted ERalpha gene in either stromal fibroblast (FSP
      ERalphaKO) or epithelial (pes-ERalphaKO) prostate cells. We found that
      circulating testosterone and fertility were not altered in FSP-ERalphaKO and pes
      ERalphaKO male mice. Prostates of FSP-ERalphaKO mice have less branching
      morphogenesis compared to that of wild-type littermates. Further analyses
      indicated that loss of stromal ERalpha leads to increased stromal apoptosis,
      reduced expression of insulin-like growth factor-1 (IGF-1) and FGF10, and
      increased expression of BMP4. Collectively, we have established the first in vivo
      prostate stromal and epithelial selective ERalphaKO mouse models and the results
      from these mice indicated that stromal fibroblast ERalpha plays important roles
      in prostatic branching morphogenesis via a paracrine fashion. Selective deletion
      of the ERalpha gene in mouse prostate epithelial cells by probasin-Cre does not
      affect the regular prostate development and homeostasis.

PMID- 22609823
TI  - Three genome-based phylogeny of Cupressaceae s.l.: further evidence for the
      evolution of gymnosperms and Southern Hemisphere biogeography.
AB  - Phylogenetic information is essential to interpret the evolution of species.
      While DNA sequences from different genomes have been widely utilized in
      phylogenetic reconstruction, it is still difficult to use nuclear genes to
      reconstruct phylogenies of plant groups with large genomes and complex gene
      families, such as gymnosperms. Here, we use two single-copy nuclear genes,
      together with chloroplast and mitochondrial genes, to reconstruct the phylogeny
      of the ecologically-important conifer family Cupressaceae s.l., based on a
      complete sampling of its 32 genera. The different gene trees generated are highly
      congruent in topology, supporting the basal position of Cunninghamia and the
      seven-subfamily classification, and the estimated divergence times based on
      different datasets correspond well with each other and with the oldest fossil
      record. These results imply that we have obtained the species phylogeny of
      Cupressaceae s.l. In addition, possible origins of all three polyploid conifers
      were investigated, and a hybrid origin was suggested for Cupressus, Fitzroya and
      Sequoia. Moreover, we found that the biogeographic history of Cupressaceae s.l.
      is associated with the separation between Laurasia and Gondwana and the further
      break-up of the latter. Our study also provides new evidence for the gymnosperm
      phylogeny.

PMID- 22609825
TI  - Abnormal brain function of the rat neonate in a prenatal 5-bromo-2'-deoxyuridine
      (BrdU)-induced developmental disorder model.
AB  - Neonatal brain function was investigated in a prenatal BrdU-induced developmental
      disorder model, which has been reported to exhibit behavioral abnormalities such
      as locomotor hyperactivity, impaired learning and memory, and lower anxiety in
      offspring. After 1h home cage deprivation we observed an increase in the number
      of c-Fos (neuronal activity marker) immunoreactive cells in several brain regions
      of the olfactory and stress-related areas in normal neonates at 11 days. Next,
      pregnant rats were exposed to 50mg/kg of BrdU from gestation days 9-15, and their
      offspring at 11 days were home-cage deprived. Compared to vehicle control, the
      number of c-Fos immunoreactive cells in BrdU group was found to be decreased in
      the piriform cortex and locus coeruleus, which are known to play an important
      role in neonatal learning and memory. We also analyzed Pearson product-moment
      correlation coefficient of the number of c-Fos immunoreactive cells, focusing on
      the piriform cortex and locus coeruleus versus numerous other brain areas (11
      areas including amygdala). Numerous significant correlations were observed in the
      vehicle control group, however, correlations of the locus coeruleus disappeared
      in the BrdU group. By observing c-Fos immunoreactivity after home cage
      deprivation our study uncovers abnormal brain functions as early as postnatal day
      11 in this disorder model. Based on these results, we propose a new histological
      approach for functional characterization of developmental disorder models.

PMID- 22609826
TI  - Modular design of an ultrahigh-intensity nanoparticle probe for cancer cell
      imaging and rapid visual detection of nucleic acids.
AB  - Based on a modular design, a novel ultrahigh-intensity nanoparticle probe was
      synthesized by orderly assembling supramolecular DNA/CdTe quantum dot nanowires
      and recognition DNA sequences on polystyrene microbeads. The probe was
      successfully applied to cancer cell imaging and visual detection of nucleic
      acids.

PMID- 22609824
TI  - Multi-copy genes that enhance the yield of mammalian G protein-coupled receptors
      in Escherichia coli.
AB  - Low yields of recombinant expression represent a major barrier to the physical
      characterization of membrane proteins. Here, we have identified genes that
      globally enhance the production of properly folded G protein-coupled receptors
      (GPCRs) in Escherichia coli. Libraries of bacterial chromosomal fragments were
      screened using two separate systems that monitor: (i) elevated fluorescence
      conferred by enhanced expression of GPCR-GFP fusions and (ii) increased binding
      of fluorescent ligand in cells producing more active receptor. Three multi-copy
      hits were isolated by both methods: nagD, encoding the ribonucleotide phosphatase
      NagD; a fragment of nlpD, encoding a truncation of the predicted lipoprotein
      NlpD, and the three-gene cluster ptsN-yhbJ-npr, encoding three proteins of the
      nitrogen phosphotransferase system. Expression of these genes resulted in a 3- to
      10-fold increase in the yields of different mammalian GPCRs. Our data is
      consistent with the hypothesis that the expression of these genes may serve to
      maintain the integrity of the bacterial periplasm and to provide a favorable
      environment for proper membrane protein folding, possibly by inducing a fine
      tuned stress response and/or via modifying the composition of the bacterial cell
      envelope.

PMID- 22609827
TI  - Uptake and translocation of 109Cd and stable Cd within tobacco plants (Nicotiana
      sylvestris).
AB  - The availability, uptake, and translocation of recently added ((109)Cd) and
      naturally occurring (stable) soil Cd within tobacco plants were compared. (109)Cd
      was added to soil in two treatments, A (0.25 MBq kg soil(-1) DW) and B (eight
      fold dose): stable Cd was measured in both treatments. Both the added and the
      stable Cd were higher in leaves and reproductive structures of the plant than in
      stalks and roots. The uptake of (109)Cd was 5.3 kBq plant(-1) for treatment A and
      36.7 kBq plant(-1) for treatment B, and about 26 MUg plant(-1) for stable Cd.
      Leaves of the tobacco plants accumulated 40-45% of the total (109)Cd and about
      50% of total stable Cd taken up by the plant. Cadmium concentration in the plant
      was three times higher than in roots and two times higher than the concentration
      in soil: the concentration in roots was lower than in the soil.

PMID- 22609828
TI  - Application of the lithiation-borylation reaction to the rapid and
      enantioselective synthesis of the bisabolane family of sesquiterpenes.
AB  - The expedient enantioselective synthesis of 5 bisabolane sesquiterpenes has been
      achieved using a common, one-pot lithiation-borylation reaction of secondary
      benzylic carbamates and either protodeboronation or oxidation to give the natural
      products in fewer than 5 steps, with high yield and >94 : 6 er.

PMID- 22609829
TI  - Dasatinib therapy results in decreased B cell proliferation, splenomegaly, and
      tumor growth in a murine model of lymphoma expressing Myc and Epstein-Barr virus
      LMP2A.
AB  - Epstein-Barr virus (EBV) infection and latency has been associated with malignant
      diseases including nasopharyngeal carcinoma, Hodgkin lymphoma, Burkitt lymphoma,
      and immune deficiency associated lymphoproliferative diseases. EBV-encoded latent
      membrane protein 2A (LMP2A) recruits Lyn and Syk kinases via its SH2-domain
      binding motifs, and modifies their signaling pathways. LMP2A transgenic mice
      develop hyperproliferative bone marrow B cells and immature peripheral B cells
      through modulation of Lyn kinase signaling. LMP2A/lambda-MYC double transgenic
      mice develop splenomegaly and cervical lymphomas starting at 8 weeks of age. We
      reasoned that targeting Lyn in LMP2A-expressing B cells with dasatinib would
      provide a therapeutic option for EBV-associated malignancies. Here, we show that
      dasatinib inhibits B cell colony formation by LMP2A transgenic bone marrow cells,
      and reverses splenomegaly and tumor growth in both a pre-tumor and a syngeneic
      tumor transfer model of EBV-associated Burkitt lymphoma. Our data support the
      idea that dasatinib may prove to be an effective therapeutic molecule for the
      treatment of EBV-associated malignancies.

PMID- 22609830
TI  - Comparing kidney perfusion using noncontrast arterial spin labeling MRI and
      microsphere methods in an interventional swine model.
AB  - OBJECTIVE: The purpose of this study was to assess the ability of a flow
      sensitive alternating inversion recovery-arterial spin labeling (FAIR-ASL)
      technique to track renal perfusion changes during pharmacologic and physiologic
      alterations in renal blood flow using microspheres as a gold standard. MATERIALS
      AND METHODS: Fluorescent microsphere and FAIR-ASL perfusion were compared in the
      cortex of the kidney for 11 swine across 4 interventional time points: (1) under
      baseline conditions, (2) during an acetylcholine and fluid bolus challenge to
      increase perfusion, (3) initially after switching to isoflurane anesthesia, and
      (4) after 2 hours of isoflurane anesthesia. In 10 of the 11 swine, a bag of ice
      was placed on the hilum of 1 kidney at the beginning of isoflurane administration
      to further reduce perfusion in 1 kidney. RESULTS: Both ASL and microspheres
      tracked the expected cortical perfusion changes (P < 0.02) across the
      interventions, including an increase in perfusion during the acetylcholine
      challenge and decrease during the administration of isoflurane. Both techniques
      also measured lower cortical perfusion in the iced compared with the non-iced
      kidneys (P <= 0.01). The ASL values were systematically lower compared with
      microsphere perfusion. Very good correlation (r = 0.81, P < 0.0001) was observed
      between the techniques, and the relationship appeared linear for perfusion values
      in the expected physiologic range (microsphere perfusion <550 mL/min/100 g)
      although ASL values saturated for perfusion >550 mL/min/100 g. CONCLUSION:
      Cortical perfusion measured with ASL correlated with microspheres and reliably
      detected changes in renal perfusion in response to physiologic challenge.

PMID- 22609831
TI  - Enabling fiber optic serotyping of pathogenic bacteria through improved anti
      fouling functional surfaces.
AB  - Significant research efforts are continually being directed towards the
      development of sensitive and accurate surface plasmon resonance biosensors for
      sequence specific DNA detection. These sensors hold great potential for
      applications in healthcare and diagnostics. However, the performance of these
      sensors in practical usage scenarios is often limited due to interference from
      the sample matrix. This work shows how the co-immobilization of glycol(PEG)
      diluents or 'back filling' of the DNA sensing layer can successfully address
      these problems. A novel SPR based melting assay is used for the analysis of a
      synthetic oligomer target as well as PCR amplified genomic DNA extracted from
      Legionella pneumophila. The benefits of sensing layer back filling on the assay
      performance are first demonstrated through melting analysis of the oligomer
      target and it is shown how back filling enables accurate discrimination of
      Legionella pneumophila serogroups directly from the PCR reaction product with
      complete suppression of sensor fouling.

PMID- 22609832
TI  - Preservation of polyunsaturated fatty acyl glycerides via intramolecular
      antioxidant coupling.
AB  - Ferulic acid and its esters are known to be effective antioxidants. Feruloyl di
      gamma-linolenoylglycerol was assessed for its ability to serve as an antioxidant
      for preventing the oxidation of its gamma-linolenoyl polyunsaturated fatty acyl
      groups in model membrane phospholipid vesicles. The molecule was incorporated
      into single-lamellar vesicles comprised of 1,2-dioleoyl-sn-glycero-3
      phosphocholine. Feruloyl di-gamma-linolenoylglycerol was found to be highly
      resistant to 2,2'-azobis(2-amidinopropane) dihydrochloride-initiated oxidation in
      comparison to di-gamma-linolenoylglycerol. Analysis of the individual fatty acyl
      chains indicated that degradation of gamma-linolenoyl groups from feruloyl di
      gamma-linolenoylglycerol proceeded much more slowly than loss of the entire
      molecule, indicating that the feruloyl moiety was preferentially oxidized. In
      vesicles incorporating di-gamma-linolenoylglycerol and an equal amount (5 mol%
      each) feruloyl dioleoylglycerol, the extent of gamma-linolenoyl protection was
      not as great as when the gamma-linolenoyl groups were molecularly combined with a
      ferulate group. These findings indicate that the ferulate group of feruloyl di
      gamma-linolenoylglycerol expresses intramolecular antioxidant activity. Direct
      coupling of polyunsaturated fatty acids with phenolic antioxidants may improve
      the oxidative stability of sensitive fatty acids in food or topical uses.

PMID- 22609833
TI  - Novel therapeutic strategies in the management of arterial hypertension.
AB  - Essential hypertension is a disease with a major impact on health worldwide, thus
      control of blood pressure seems to be a key component of cardiovascular disease
      prevention. Despite considerable advances in the treatment of hypertension,
      effective management remains poor and new strategies to control high blood
      pressure and cardiovascular risk reduction are required. These seem to be divided
      into two major categories: those seeking to advance blood pressure-lowering
      efficacy of already existing agents, and others related to novel approaches, both
      pharmacological and non-pharmacological. Moreover, numerous clinical trials have
      evaluated the use of nutritional supplements in the prevention of cardiovascular
      diseases and in achievement of optimal blood pressure control. Additionally, the
      advent of interventional techniques, such as carotid baroreceptor stimulation and
      renal ablation of sympathetic nerve activity, seems to be proved effective in
      cases where medical management and lifestyle modifications are insufficient.
      Genetic technology, which has advanced tremendously over the past few years,
      could assist novel treatment options in hypertensive patients, such as RNA
      interference targeting hypertension-related genes. However, continued efforts
      must progress in these areas and the effects of therapeutic strategies in
      hypertensive patients need to be further explored in larger trials over a longer
      period of time.

PMID- 22609834
TI  - 18beta-Glycyrrhetinic acid preferentially blocks late Na current generated by
      DeltaKPQ Nav1.5 channels.
AB  - AIM: To compare the effects of two stereoisomeric forms of glycyrrhetinic acid on
      different components of Na(+) current, HERG and Kv1.5 channel currents. METHODS:
      Wild-type (WT) and long QT syndrome type 3 (LQT-3) mutant DeltaKPQ Nav1.5
      channels, as well as HERG and Kv1.5 channels were expressed in Xenopus oocytes.
      In addition, isolated human atrial myocytes were used. Two-microelectrode voltage
      clamp technique was used to record the voltage-activated currents. RESULTS:
      Superfusion of 18beta-glycyrrhetinic acid (18beta-GA, 1-100 MUmol/L) blocked both
      the peak current (I(Na,P)) and late current (I(Na,L)) generated by WT and
      DeltaKPQ Nav1.5 channels in a concentration-dependent manner, while 18alpha
      glycyrrhetinic acid (18alpha-GA) at the same concentrations had no effects.
      18beta-GA preferentially blocked I(Na,L) (IC(50)=37.2 +/- 14.4 MUmol/L) to
      I(Na,P) (IC(50)=100.4 +/- 11.2 MUmol/L) generated by DeltaKPQ Nav1.5 channels. In
      human atrial myocytes, 18beta-GA (30 MUmol/L) inhibited 47% of I(Na,P) and 87% of
      I(Na,L) induced by Anemonia sulcata toxin (ATX-II, 30 nmol/L). Superfusion of
      18beta-GA (100 MUmol/L) had no effects on HERG and Kv1.5 channel currents.
      CONCLUSION: 18beta-GA preferentially blocked the late Na current without
      affecting HERG and Kv1.5 channels.

PMID- 22609835
TI  - Melatonin reduces acute lung inflammation, edema, and hemorrhage in heatstroke
      rats.
AB  - AIM: To assess the therapeutic effect of melatonin on heat-induced acute lung
      inflammation and injury in rats. METHODS: Heatstroke was induced by exposing
      anesthetized rats to heat stress (36  degrees C, 100 min). Rats were treated with
      vehicle or melatonin (0.2, 1, 5 mg/kg) by intravenous administration 100 min
      after the initiatioin of heatstroke and were allowed to recover at room
      temperature (26  degrees C). The acute lung injury was quantified by
      morphological examination and by determination of the volume of pleural exudates,
      the number of polymorphonuclear (PMN) cells, and the myeloperoxidase (MPO)
      activity. The concentrations of tumor necrosis factor, interleukin (IL)-1beta, IL
      6, and IL-10 in bronchoalveolar fluid (BALF) were measured by ELISA. Nitric oxide
      (NO) level was determined by Griess method. The levels of glutamate and lactate
      to-pyruvate ratio were analyzed by CMA600 microdialysis analyzer. The
      concentrations of hydroxyl radicals were measured by a procedure based on the
      hydroxylation of sodium salicylates leading to the production of 2,3
      dihydroxybenzoic acid (DHBA). RESULTS: Melatonin (1 and 5 mg/kg) significantly
      (i) prolonged the survival time of heartstroke rats (117 and 186 min vs 59 min);
      (ii) attenuated heatstroke-induced hyperthermia and hypotension; (iii) attenuated
      acute lung injury, including edema, neutrophil infiltration, and hemorrhage
      scores; (iv) down-regulated exudate volume, BALF PMN cell number, and MPO
      activity; (v) decreased the BALF levels of lung inflammation response cytokines
      like TNF-alpha, interleukin (IL)-1beta, and IL-6 but further increased the level
      of an anti-inflammatory cytokine IL-10; (vi) reduced BALF levels of glutamate,
      lactate-to-pyruvate ratio, NO, 2,3-DHBA, and lactate dehydrogenase. CONCLUSION:
      Melatonin may improve the outcome of heatstroke in rats by attenuating acute lung
      inflammation and injury.

PMID- 22609836
TI  - Comparison of the effects of DC031050, a class III antiarrhythmic agent, on hERG
      channel and three neuronal potassium channels.
AB  - AIM: This study was conducted to test the selectivity of DC031050 on cardiac and
      neuronal potassium channels. METHODS: Human ether-a-go-go related gene (hERG),
      KCNQ and Kv1.2 channels were expressed in CHO cells. The delayed rectifier
      potassium current (I(K)) was recorded from dissociated hippocampal pyramidal
      neurons of neonatal rats. Whole-cell voltage patch clamp was used to record the
      voltage-activated potassium currents. Drug-containing solution was delivered
      using a RSC-100 Rapid Solution Changer. RESULTS: Both DC031050 and dofetilide
      potently inhibited hERG currents with IC(50) values of 2.3 +/- 1.0 and 17.9 +/-
      1.2 nmol/L, respectively. DC031050 inhibited the I(K) current with an IC(50)
      value of 2.7 +/- 1.5 MUmol/L, which was >1000 times the concentration required to
      inhibit hERG current. DC031050 at 3 MUmol/L did not significantly affect the
      voltage-dependence of the steady activation, steady inactivation of I(K), or the
      rate of I(K) from inactivation. Intracellular application of DC031050 (5 MUmol/L)
      was insufficient to inhibit I(K). DC031050 up to 10 MUmol/L had no effects on
      KCNQ2 and Kv1.2 channel currents. CONCLUSION: DC031050 is a highly selective hERG
      potassium channel blocker with a substantial safety margin of activity over
      neuronal potassium channels, thus holds significant potential for therapeutic
      application as a class III antiarrhythmic agent.

PMID- 22609837
TI  - Efficacy of zoledronic acid in treatment of teoarthritis is dependent on the
      disease progression stage in rat medial meniscal tear model.
AB  - AIM: To investigate whether the stage of osteoarthritis (OA) progression
      influenced the efficacy of the third-generation bisphosphonate zoledronic acid in
      a rat medial meniscal tear model. METHODS: Medial meniscal tear (MMT) was
      surgically induced in adult male Sprague Dawley rats. Zoledronic acid (ZOL, 100
      MUg/kg, sc, twice a week) was administered starting immediately, early (from 4
      weeks) or late (from 8 weeks) after OA induction. The degeneration of articular
      cartilage was evaluated with toluidine blue O staining. Subchondral bone
      remodeling was evaluated with X-ray micro-CT scanning. Joint pain was measured
      with respect to weight-bearing asymmetry. Calcitonin gene-related peptide (CGRP)
      expression in dorsal root ganglia (DRGs) was examined using immunofluorescence
      analysis. The afferent neurons in DRGs innervating the joint were identified by
      retrograde labeling with fluorogold. RESULTS: Progressive cartilage loss was
      observed during 12 weeks after OA induction. Subchondral bone remodeling
      manifested as increased bone resorption at early stage (4 weeks), but as
      increased bone accretion at advanced stages (8 weeks). Immediately and early ZOL
      administration significantly improved subchondral microstructural parameters,
      attenuated cartilage degeneration, reduced weight-bearing asymmetry and CGRP
      expression, whereas the late ZOL administration had no significant effects.
      CONCLUSION: The stage of OA progression influences the efficacy of ZOL in
      treating joint degeneration and pain. To obtain the maximum efficacy,
      bisphosphonate treatment should be initiated in rat with early stages of OA
      pathogenesis.

PMID- 22609840
TI  - Significantly increased pregnancy rates after laparoscopic restorative
      proctocolectomy: a cross-sectional study.
AB  - OBJECTIVE: To assess the impact of a laparoscopic approach on female fecundity in
      ileoanal pouch surgery. BACKGROUND: Restorative proctocolectomy with ileal pouch
      anal anastomosis (IPAA) is associated with tubal factor infertility in female
      patients. Different studies showed less adhesion formation after laparoscopic
      colectomy. The relation between laparoscopic pouch surgery and fertility,
      however, has not been studied so far. METHODS: This cross-sectional study was
      carried out in 3 university hospitals in the Netherlands and in Belgium. Female
      patients older than 18 years that had IPAA under the age of 41 were eligible for
      inclusion (n = 179). We sent them a questionnaire addressing medical and
      fertility history. The primary endpoint was time to first spontaneous pregnancy
      after IPAA. This study has been registered with ISRCTN.org (ISRCTN85421386).
      RESULTS: Of 179 eligible patients, 160 (89%) returned the questionnaire. After
      IPAA, 50 (31%) patients attempted to conceive. Of these, 23 (46%) had undergone
      open and 27 (54%) had undergone laparoscopic IPAA. Patient characteristics were
      similar in both groups. Indications for surgery were ulcerative colitis (UC) in
      37 patients, familial adenomatous polyposis (FAP) in 12 patients, and colonic
      ischemia in 1 patient. A Kaplan-Meier survival function was plotted for time to
      first spontaneous pregnancy and showed a higher pregnancy rate after laparoscopic
      IPAA (log-rank, P = 0.023). Similarly, subsequent survival analysis for all
      patients with UC showed an increased pregnancy rate for the laparoscopic group
      (log-rank, P = 0.033). CONCLUSIONS: Pregnancy rates are significantly higher
      after laparoscopic IPAA. This makes the laparoscopic approach the method of
      choice in young women.

PMID- 22609838
TI  - Anti-CHMP5 single chain variable fragment antibody retrovirus infection induces
      programmed cell death of AML leukemic cells in vitro.
AB  - AIM: Over-expressed CHMP5 was found to act as oncogene that probably participated
      in leukemogenesis. In this study, we constructed the CHMP5 single chain variable
      fragment antibody (CHMP5-scFv) retrovirus and studied the changes of programmed
      cell death (PCD) of AML leukemic cells after infection by the retrovirus.
      METHODS: The anti-CHMP5 KC14 hybridoma cell line was constructed to generate
      monoclonal antibody of CHMP5. The protein expression of CHMP5 was studied using
      immunofluorescence analysis. pMIG-CHMP5 scFv antibody expressible retroviral
      vector was constructed to prepare CHMP5-scFv retrovirus. AML leukemic U937 cells
      were infected with the retrovirus, and programmed cell death was studied using
      confocal microscope, FCM and Western blot. RESULTS: We obtained a monoclonal
      antibody of CHMP5, and found the expression of CHMP5 was up-regulated in the
      leukemic cells. After U937 cells were infected with CHMP5-scFv retrovirus, CHMP5
      protein was neutralized. Moreover, the infection resulted in a significant
      increase in apoptosis and necrosis of U937 cells. In U937 cells infected with
      CHMP5-scFv retrovirus, apoptosis-inducing factor (AIF)-mediated caspase
      independent necrotic PCD was activated, but autophagic programmed cell death was
      not observed. Neither the intrinsic nor extrinsic apoptotic PCD pathway was
      activated. The granzyme B/perforin-mediated caspase-dependent apoptotic PCD
      pathway was not activated. CONCLUSION: CHMP5-scFv retrovirus can neutralize the
      abnormally high levels of the CHMP5 protein in the cytosol of AML leukemic U937
      cells, thereby inducing the programmed cell death of the leukemic cells via AIF
      mediated caspase-independent necrosis and apoptosis.

PMID- 22609841
TI  - Antibacterial efficacy of silver-impregnated polyelectrolyte multilayers
      immobilized on a biological dressing in a murine wound infection model.
AB  - OBJECTIVE: To investigate the antibacterial effect of augmenting a biological
      dressing with polymer films containing silver nanoparticles. BACKGROUND:
      Biological dressings, such as Biobrane, are commonly used for treating partial
      thickness wounds and burn injuries. Biological dressings have several advantages
      over traditional wound dressings. However, as many as 19% of wounds treated with
      Biobrane become infected, and, once infected, the Biobrane must be removed and a
      traditional dressing approach should be employed. Silver is a commonly used
      antimicrobial in wound care products, but current technology uses cytotoxic
      concentrations of silver in these dressings. We have developed a novel and facile
      technology that allows immobilization of bioactive molecules on the surfaces of
      soft materials, demonstrated here by augmentation of Biobrane with
      nanoparticulate silver. Surfaces modified with nanometer-thick polyelectrolyte
      multilayers (PEMs) impregnated with silver nanoparticles have been shown
      previously to result in in vitro antibacterial activity against Staphylococcus
      epidermidis at loadings of silver that are noncytotoxic. METHODS: We demonstrated
      that silver-impregnated PEMs can be nondestructively immobilized onto the surface
      of Biobrane (Biobrane-Ag) and determined the in vitro antibacterial activity of
      Biobrane-Ag with Staphylococcus aureus. In this study, we used an in vivo wound
      infection model in mice induced by topical inoculation of S aureus onto full
      thickness 6-mm diameter wounds. After 72 hours, bacterial quantification was
      performed. RESULTS: Wounds treated with Biobrane-Ag had significantly (P < 0.001)
      fewer colony-forming units than wounds treated with unmodified Biobrane (more
      than 4 log10 difference). CONCLUSIONS: The results of our study indicate that
      immobilizing silver-impregnated PEMs on the wound-contact surface of Biobrane
      significantly reduces bacterial bioburden in full-thickness murine skin wounds.
      Further research will investigate whether this construct can be considered for
      human use.

PMID- 22609842
TI  - A broad assessment of clinical outcomes after laparoscopic antireflux surgery.
AB  - OBJECTIVES: There is considerable discussion regarding "success" rates for
      laparoscopic antireflux surgery (LARS). We hypothesized that, in part, this was a
      reflection of the outcome variables used. We, therefore, defined 8 specific
      variables (within 3 categories) and assessed outcomes for each in a large cohort
      of patients. METHODS: Four hundred patients (208 women; median age 52 years old)
      who underwent LARS at the University of Washington from 1993 to 2008 were given a
      comprehensive questionnaire to assess various aspects of their outcomes from
      LARS. In addition, we analyzed all functional studies and all endoscopies
      performed in these patients in our institution, whether the patients had symptoms
      or not, and compared the findings to all available preoperative values. RESULTS:
      The median follow-up was 92 (6-175) months. CONCLUSIONS: The success or failure
      of LARS cannot be defined in a single domain. A comprehensive analysis of
      outcomes requires categorization that includes symptom response, side-effects,
      patient's perception and objective measurement of acid exposure, mucosal
      integrity, and the need for additional medical or surgical treatment. Only then
      can patients and physicians better understand the role of LARS and make informed
      decisions.

PMID- 22609843
TI  - Sleeve gastrectomy with transit bipartition: a potent intervention for metabolic
      syndrome and obesity.
AB  - OBJECTIVE: To present 5-year results of sleeve gastrectomy (SG) with transit
      bipartition (TB) as a metabolic intervention for obesity. BACKGROUND: Recent data
      suggest that high glycemic index foods may lead to a hormonally hyperactive
      proximal gut and a hypoactivate distal gut, which are linked to metabolic
      syndrome. TB was designed to counterbalance these effects. METHODS: A total of
      1020 obese patients with body mass index (BMI) ranging from 33 to 72 Kg/m
      underwent SG and TB (SG + TB). TB creates a gastroileal anastomosis in the antrum
      after the SG; nutrient transit is maintained in the duodenum, avoiding blind
      loops and minimizing malabsorption. The stomach retains 2 outflow pathways. A
      lateral enteroanastomosis connects both segments at 80 cm proximal to the cecum.
      RESULTS: Adequate follow-up data were collected in 59.1% of patients from 4
      months to 5 years. The average percent of excess BMI loss was 91%, 94%, 85%, 78%,
      and 74% in the first, second, third, fourth, and fifth year, respectively.
      Patients experienced early satiety and major improvement in presurgical
      comorbidities, including diabetes (86% in remission), following surgery. Two
      deaths occurred (0.2%). Other surgical complications occurred in 6% of patients.
      Signs of malabsorption were rare. CONCLUSIONS: SG + TB is a simple procedure that
      results in rapid weight loss and remission or major improvement of comorbidities.
      Strictly aiming at physiological correction, TB avoids prostheses, narrow
      anastomoses, excluded segments, and malabsorption. Weight and comorbidities are
      much improved. Diabetes is improved without duodenal exclusion. TB is an
      excellent complement to an SG.

PMID- 22609844
TI  - Preoperative CT scan helps to predict the occurrence of severe pancreatic fistula
      after pancreaticoduodenectomy.
AB  - OBJECTIVE: To assess the influence of body fat distribution, estimated by a
      preoperative computed tomographic (CT) scan, on pancreatic fistula (PF) risk
      after pancreaticoduodenectomy (PD). BACKGROUND: Pancreatic fatty infiltration is
      a predictive factor of PF, but accurate preoperative assessment is challenging.
      We hypothesized that it could be associated with an increased visceral obesity
      and could be assessed preoperatively. METHODS: Over 18 months, 103 consecutive
      patients with PD and pancreaticogastrostomy were studied. Demographic,
      radiologic, and pathologic data were correlated to PF occurrence. Radiologic data
      included on a nonenhanced CT acquisition: pancreas, spleen, and liver density
      measures (Dpancreas, Dspleen, and Dliver [densities of the pancreas, spleen, and
      liver in hounsfield units], respectively), retro-renal fat thickness, and at the
      level of the umbilicus, total, visceral, and subcutaneous fat area (TFA [total
      fat area], VFA [visceral fat area], and SFA [subcutaneous fat area],
      respectively). Pancreatic fatty infiltration was graded histologically. Logistic
      regression analysis was used to identify independent predictors of PF-graded B
      and C according to the International Study Group on the Pancreatic Fistula.
      RESULTS: Among the 103 patients, 37% (n = 38) developed a PF (47.4% grade A,
      39.5% grade B, and 13.1% grade C). PF risk was correlated with pancreatic fatty
      infiltration (P = 0.017). In univariate analysis, male gender (P = 0.023), body
      mass index (BMI) over 25 kg/m (P = 0.02), retro-renal fat thickness over 15 mm (P
      = 0.006), TFA over the median (>233 cm; P = 0.023), and VFA over the median (>84
      cm; P < 0.0001) were significantly associated with an increased risk of
      symptomatic PF (grade B and C). In multivariate analysis, VFA greater than 84 cm
      (OR = 8.16, P = 0.002) was the only independent predictive factor of grade B or C
      PF. Using the same model, a VFA greater than 84 cm was the only independent
      factor associated with the presence of fatty pancreas on pathologic examination.
      CONCLUSIONS: Preoperative assessment of body fat distribution by a CT scan, as a
      surrogate for fatty pancreas infiltration, can help to predict the occurrence of
      clinically significant PF after PD.

PMID- 22609845
TI  - Striking the right balance: optimizing conditioning regimens for unrelated donor
      bone marrow transplant for severe aplastic anemia.

PMID- 22609846
TI  - Prevalence of intracellular galectin-1-expressing lymphocytes in umbilical cord
      blood in comparison with adult peripheral blood.
AB  - Umbilical cord blood (UCB) is a promising alternative for the treatment of
      hematological malignancies. The lower immune reactivity of UCB lymphocytes is a
      well-known phenomenon; however, immune tolerance mechanisms are not fully
      elucidated. Galectin-1 has strong immunosuppressive properties and plays a key
      role in the regulation of immune reactivity. We aimed to determine the properties
      of intracellular galectin-1 (Gal-1)-producing cells within CD3, CD4, CD8,
      regulatory T (Treg), and natural killer (NK) cells in UCB compared to adult
      peripheral blood (APB). We took peripheral blood samples from 22 healthy adults
      and cord blood samples from 19 healthy, term neonates. Intracellular Gal-1
      expression was determined by flow cytometry in the above subsets. Furthermore, we
      assessed the prevalence of naive and memory T cells that play a role in the
      regulation of immune reactivity. We also performed functional analyses to assess
      the effect of exogenous Gal-1 on the rate of proliferation of T lymphocytes
      isolated from APB and UCB. The prevalence of intracellular Gal-1-expressing CD3,
      CD4, CD8, Treg and NK lymphocytes was lower in UCB than in APB. However, their
      capability to produce Gal-1 reaches the level seen in adults. The prevalence of
      naive cells was higher, whereas that of central and effector memory T cells was
      lower in UCB compared with APB. Lower Gal-1-producing cell proportion might be
      due to the naivety of neonatal lymphocytes, as indicated by the positive
      correlation detected between the number of CD3 lymphocytes expressing
      intracellular Gal-1 and the prevalence of memory T cells. The intracellular
      expression of Gal-1 may be down-regulated in neonatal lymphocytes due to the
      already reduced immune reactivity of UCB. In contrast with previous findings, our
      results indicate that the administration of exogenous Gal-1 failed to decrease
      the rate of proliferation in T lymphocytes isolated from either APB or UCB. This
      suggests that Gal-1-expressing lymphocytes are unlikely to play a major role in
      mitigating the immune reactivity of UCB.

PMID- 22609848
TI  - Lack of association between dopamine receptor D4 variable numbers of tandem
      repeats gene polymorphism and smoking.
AB  - Nicotine addiction, related to cigarette smoking, develops as a product of the
      complex interactions between social, environmental and genetic factors. Genes
      encoding the components of the dopaminergic system are thought to be associated
      with smoking. Literature data showed not only an association, but also a lack of
      association between variable number of tandem repeats (VNTR) polymorphism located
      in the third exon of dopamine D4 receptor (DRD4) gene and smoking. Repetitive
      sequence of DRD4 VNTR is 48 bp long and maximum 11 tandem copies were reported in
      humans. Presence of alleles with 6 and more repeats (i.e. long alleles) was
      associated with greater tendency to novelty seeking and addictive behaviors than
      the presence of 5 and less alleles (short alleles). The aim of this study was to
      determine the association between VNTR in DRD4 gene and present smoking status in
      ethnically homogenous Caucasian population from the Eastern European (Croatian)
      origin. Genotyping was done in 565 healthy subjects, 511 men and 54 women,
      respectively, who were subdivided into 176 smokers and 389 nonsmokers. Logistic
      regression analyses, adjusted for age and sex, revealed the lack of significant
      (p>0.05) effect of the 4/4, 4/7 and 7/7 genotypes, or carriers of the long and
      short allele, or all genotypes of the DRD4 VNTR on smoking status. The results of
      this study failed to confirm the hypothesis that long allele of the DRD4 VNTR is
      associated with smoking status in Caucasian subjects.

PMID- 22609847
TI  - Gene therapy for muscular dystrophy: lessons learned and path forward.
AB  - Our Translational Gene Therapy Center has used small molecules for exon skipping
      and mutation suppression and gene transfer to replace or provide surrogate genes
      as tools for molecular-based approaches for the treatment of muscular
      dystrophies. Exon skipping is targeted at the pre-mRNA level allowing one or more
      exons to be omitted to restore the reading frame. In Duchenne Muscular Dystrophy
      (DMD), clinical trials have been performed with two different oligomers, a 2'O
      methyl-ribo-oligonucleoside-phosphorothioate (2'OMe) and a phosphorodiamidate
      morpholino (PMO). Both have demonstrated early evidence of efficacy. A second
      molecular approach involves suppression of stop codons to promote readthrough of
      the DMD gene. We have been able to establish proof of principle for mutation
      suppression using the aminoglycoside, gentamicin. A safer, orally administered,
      alternative agent referred to as Ataluren (PTC124) has been used in clinical
      trials and is currently under consideration for approval by the FDA. Using a gene
      therapy approach, we have completed two trials and have initiated a third. For
      DMD, we used a mini-dystrophin transferred in adeno-associated virus (AAV). In
      this trial an immune response was seen directed against transgene product, a
      quite unexpected outcome that will help guide further studies. For limb girdle
      muscular dystrophy 2D (alpha-sarcoglycan deficiency), the transgene was again
      transferred using AAV but in this study, a muscle specific creatine kinase
      promoter controlled gene expression that persisted for six months. A third gene
      therapy trial has been initiated with transfer of the follistatin gene in AAV
      directly to the quadriceps muscle. Two diseases with selective quadriceps muscle
      weakness are undergoing gene transfer including sporadic inclusion body myositis
      (sIBM) and Becker muscular dystrophy (BMD). Increasing the size and strength of
      the muscle is the goal of this study. Most importantly, no adverse events have
      been encountered in any of these clinical trials.

PMID- 22609849
TI  - Relax with CouchDB--into the non-relational DBMS era of bioinformatics.
AB  - With the proliferation of high-throughput technologies, genome-level data
      analysis has become common in molecular biology. Bioinformaticians are developing
      extensive resources to annotate and mine biological features from high-throughput
      data. The underlying database management systems for most bioinformatics software
      are based on a relational model. Modern non-relational databases offer an
      alternative that has flexibility, scalability, and a non-rigid design schema.
      Moreover, with an accelerated development pace, non-relational databases like
      CouchDB can be ideal tools to construct bioinformatics utilities. We describe
      CouchDB by presenting three new bioinformatics resources: (a) geneSmash, which
      collates data from bioinformatics resources and provides automated gene-centric
      annotations, (b) drugBase, a database of drug-target interactions with a web
      interface powered by geneSmash, and (c) HapMap-CN, which provides a web interface
      to query copy number variations from three SNP-chip HapMap datasets. In addition
      to the web sites, all three systems can be accessed programmatically via web
      services.

PMID- 22609850
TI  - The meaning of life prognosis disclosure for Japanese cancer patients: a
      qualitative study of patients' narratives.
AB  - OBJECTIVE: Recently, disclosure of cancer diagnosis is common in Japan, but
      significant variability in patient preference of prognostic disclosure poses
      difficult questions for doctors. The aim of this study was to understand the
      reasons for wanting or not wanting to know life prognosis and how the information
      was interpreted and utilized by the patients. METHODS: The study was based on
      narrative interviews with 42 women with breast cancer and 49 men with prostate
      cancer, in varying stages. A qualitative and interpretive approach was taken,
      combining thematic analysis with constant comparison. RESULTS: While some of the
      participants voluntarily asked for prognosis to prepare themselves for the end of
      life, others were shocked by unexpected and unilateral disclosure. Some obtained
      prognostic information from books and websites. Some preferred to remain unaware
      of life prognosis, partly because they feared it would become a self-fulfilling
      prophecy. DISCUSSION: The major problem underlying the practice of prognostic
      disclosure is the absence of mutual understanding of how such information will be
      utilized. These findings affirm that it should be used to empower patients to
      participate in the decision-making process.

PMID- 22609851
TI  - The organochlorine o,p'-DDT plays a role in coactivator-mediated MAPK crosstalk
      in MCF-7 breast cancer cells.
AB  - BACKGROUND: The organochlorine dichlorodiphenyltrichloroethane (DDT), a known
      estrogen mimic and endocrine disruptor, has been linked to animal and human
      disorders. However, the detailed mechanism(s) by which DDT affects cellular
      physiology remains incompletely defined. OBJECTIVES: We and others have shown
      that DDT activates cell-signaling cascades, culminating in the activation of
      estrogen receptor-dependent and -independent gene expression. Here, we identify a
      mechanism by which DDT alters cellular signaling and gene expression, independent
      of the estrogen receptor. METHODS: We performed quantitative polymerase chain
      reaction array analysis of gene expression in MCF-7 breast cancer cells using
      either estradiol (E2) or o,p'-DDT to identify distinct cellular gene expression
      responses. To elucidate the mechanisms by which DDT regulates cell signaling, we
      used molecular and pharmacological techniques. RESULTS: E2 and DDT treatment both
      altered the expression of many of the genes assayed, but up-regulation of
      vascular endothelial growth factor A (VEGFA) was observed only after DDT
      treatment, and this increase was not affected by the pure estrogen receptor alpha
      antagonist ICI 182780. Furthermore, DDT increased activation of the HIF-1
      response element (HRE), a known enhancer of the VEGFA gene. This DDT-mediated
      increase in HRE activity was augmented by the coactivator CBP (CREB-binding
      protein) and was dependent on the p38 pathway. CONCLUSIONS: DDT up-regulated the
      expression of several genes in MCF-7 breast cancer cells that were not altered by
      treatment with E2, including VEGFA. We propose that this DDT-initiated, ER
      independent stimulation of gene expression is due to DDT's ability to initiate
      crosstalk between MAPK (mitogen-activated protein kinase) signaling pathways and
      transcriptional coactivators.

PMID- 22609852
TI  - Micronucleus frequency in human lymphocytes after exposure to diphenylamine in
      vitro.
AB  - Diphenylamine (DPA) is an antioxidant compound that occurs naturally in several
      vegetables. It is widely applied in agriculture for preservation of the quality
      of apples and pears, and used for controlling superficial scald, a disorder that
      renders fruits of a number of apple cultivars unfit for the market. Because of
      its anti-oxidative properties, DPA also has several industrial applications. The
      potential genotoxic effect of DPA on human lymphocytes has previously been
      investigated in only two studies, which focused on detection of chromosome
      aberrations and sister chromatid exchange, respectively. In the present analysis,
      we evaluated micronucleus (MN) formation in freshly isolated human peripheral
      lymphocytes exposed to different concentrations (0.625, 1.25, 2.50, 5.0 and
      10.0MUg/ml) of DPA. Peripheral venous blood was collected from ten healthy
      subjects, and a total of 10,000 bi-nucleated cells were analyzed. Results
      indicated that DPA significantly increased the micronucleus frequency at
      concentrations of 1.25MUg/ml and higher. Significant differences in the MN
      frequency were also found between the lower dose (0.625MUg/ml) and all other
      doses tested, with the exception of 1.25MUg/ml. Our results indicate a potential
      cytogenetic effect of DPA on human cells in vitro and require further in vivo
      studies to clarify the actual genotoxicity of this compound and the consequent
      risks for human health.

PMID- 22609853
TI  - Synthesis of adenosine functionalized metal immobilized magnetic nanoparticles
      for highly selective and sensitive enrichment of phosphopeptides.
AB  - A new type of IMAC material, with ATP as the chelating ligand, was synthesized
      and applied to capture phosphopeptides. For the first time, the approach for
      phosphopeptide enrichment could provide selectivity under 5000-fold dilution by
      nonphosphopeptides, and sensitivity of on-target enrichment at 3 amol.

PMID- 22609854
TI  - MLN0905, a small-molecule plk1 inhibitor, induces antitumor responses in human
      models of diffuse large B-cell lymphoma.
AB  - Diffuse large B-cell lymphoma (DLBCL) is the most common of the non-Hodgkin
      lymphomas, accounting for up to 30% of all newly diagnosed lymphoma cases.
      Current treatment options for this disease are effective, but not always
      curative; therefore, experimental therapies continue to be investigated. We have
      discovered an experimental, potent, and selective small-molecule inhibitor of
      PLK1, MLN0905, which inhibits cell proliferation in a broad range of human tumor
      cells including DLBCL cell lines. In our report, we explored the pharmacokinetic,
      pharmacodynamic, and antitumor properties of MLN0905 in DLBCL xenograft models
      grown in mice. These studies indicate that MLN0905 modulates the pharmacodynamic
      biomarker phosphorylated histone H3 (pHisH3) in tumor tissue. The antitumor
      activity of MLN0905 was evaluated in three human subcutaneous DLBCL xenograft
      models, OCI LY-10, OCI LY-19, and PHTX-22L (primary lymphoma). In each model,
      MLN0905 yielded significant antitumor activity on both a continuous (daily) and
      intermittent dosing schedule, underscoring dosing flexibility. The antitumor
      activity of MLN0905 was also evaluated in a disseminated xenograft (OCI LY-19)
      model to better mimic human DLBCL disease. In the disseminated model, MLN0905
      induced a highly significant survival advantage. Finally, MLN0905 was combined
      with a standard-of-care agent, rituximab, in the disseminated OCI LY-19 xenograft
      model. Combining rituximab and MLN0905 provided both a synergistic antitumor
      effect and a synergistic survival advantage. Our findings indicate that PLK1
      inhibition leads to pharmacodynamic pHisH3 modulation and significant antitumor
      activity in multiple DLBCL models. These data strongly suggest evaluating PLK1
      inhibitors as DLBCL anticancer agents in the clinic.

PMID- 22609855
TI  - Dietary Yucca schidigera supplementation reduces arsenic-induced oxidative stress
      in Swiss albino mice.
AB  - The aim of this study was to clarify the effects of dietary supplementation with
      Yucca schidigera (Ys) on lipid peroxidation (LPO), antioxidant activity, some
      biochemical parameters and histopathological changes in arsenic-exposed mice.
      Forty Swiss albino male mice were divided into five equal groups. Group I
      (control group) was given normal diet and tap water for 28 days. Group II
      (arsenic group) was given normal diet and 100 mg/L arsenic along with drinking
      water for 28 days. Groups III-V were given three different doses of Ys (50, 100
      and 200 mg/kg) in supplemented diet and arsenic (100 mg/L) along with drinking
      water throughout the entire period of 28 days. The arsenic significantly
      increased serum biochemical parameters and malondialdehyde levels in blood and
      tissue. However, arsenic significantly decreased tissue glutathione
      concentration, erythrocyte superoxide dismutase and catalase activities. In
      contrast, dietary supplementation of Ys, in a dose-dependent manner, resulted in
      reversal of arsenic-induced oxidative stress, LPO and activities of antioxidant
      enzymes. Moreover, Ys also exhibited protective action against the arsenic
      induced focal gliosis and hyperemi in brain, necrosis and degeneration in liver,
      degeneration and dilatation in Bowman's capsule of kidney and hyaline
      degeneration in heart tissue of mice. Consequently, our results demonstrate that
      Ys especially high-dose supplementation in diet decreases arsenic-induced
      oxidative stress and enhances the antioxidant defence mechanism and regenerate of
      tissues in Swiss albino mice.

PMID- 22609856
TI  - In vitro biomonitoring of the genotoxic and oxidative potentials of two commonly
      eaten insects in southwestern Nigeria.
AB  - In this study, the cytogenetic and oxidative effects of water soluble extracts of
      two commonly eaten insects, Zonocerus variegatus (Orthoptera: Pyrgomorphidae) and
      Oryctes boas (Solanales: Solanaceae), in southwestern Nigeria were evaluated on
      cultured human blood cells. The extracts were added to the cultures at various
      concentrations (0-2000 ppm). The chromosome aberration and micronucleus tests
      were used to find out the DNA and chromosomal damage potentials in vitro by
      aqueous insect extracts. To assess the oxidative effects of these insect
      extracts, total antioxidant capacity (TAC) and total oxidant status (TOS) levels
      were also measured. Our results indicated that these extracts did not show
      genotoxic effects at the tested concentrations. However, the extracts caused dose
      dependent alterations in both TAC and TOS levels. Based on the findings, it was
      concluded that the studied insects can be consumed safely, but it is necessary to
      consider the cellular damages that are likely to appear depending on the
      oxidative stress. We also suggest that this in vitro approach for oxidative and
      genotoxicity assessments may be useful to compare the potential health risks of
      edible insects.

PMID- 22609857
TI  - Ameliorating effects of curcumin and vitamin E on diazinon-induced oxidative
      damage in rat liver and erythrocytes.
AB  - The aim of this study was to evaluate the protective effects of vitamin E and/or
      curcumin against diazinon (DZN) (an organophosphorus insecticide)-induced
      toxicity of blood, liver and erythrocyte markers of male Wistar rats. The
      exposure of rats to DZN for 21 days provoked significant changes in red blood
      cell counts and hemoglobin. Results showed that lipid peroxidation increased
      significantly in DZN-treated rats, as evidenced by high liver and erythrocyte
      thiobarbituric acid reactive substance levels. Alteration of the antioxidant
      system in DZN-treated rats was confirmed by the significant decrease in the
      activity of catalase, glutathione peroxidase and glutathione-S-transferase,
      accompanied by a decline in reduced glutathione content in both tissues. On the
      other hand, a significant increase in the activities of plasma aspartate
      transaminase, alanine transaminase, lactate dehydrogenase and alkaline
      phosphatase was observed in the rats treated with DZN. However, the
      administration of vitamin E and curcumin has ameliorated the previous markers. In
      conclusion, our results indicate that the natural antioxidants like vitamin E and
      curcumin can effectively lower the erythrocytes and hepatic injuries induced by
      DZN as monitored by lipid peroxides, antioxidant enzyme activities and sensitive
      serum enzyme levels.

PMID- 22609858
TI  - Health hazards among workers in plastic industry.
AB  - Styrene is a basic building block for manufacturing thousands of products
      throughout the world. The present study aimed to (1) detect the presence of
      styrene and/or its metabolites in the workers in one of the Egyptian plastic
      factories; (2) demonstrate some common health effects of styrene exposure among
      the same group by some laboratory investigations and compare them with the
      unexposed healthy individuals; and (3) correlate the duration of styrene exposure
      and its level in the blood with the severity of the demonstrated health effects.
      This study was conducted in one of Egyptian plastic factories. The exposed group
      was 40 male workers, ranging in age from 18 to 33 years (23.20 +/- 4.09), working
      12 h/day with 1 day off, and working without any protective equipment. A control
      group of 50 unexposed healthy males matched with the exposed group for age (21-35
      yrs (23.40 +/- 4.05)), sex, socioeconomic status, and smoking habit is selected.
      Written individual consent is obtained from all participants followed by (a) a
      full medical and occupational history and full clinical examination; (b)
      ventilatory function tests: forced vital capacity (FVC), slow vital capacity,
      forced expiratory volume in the 1st second (FEV1)%, FEV1/FVC%, peak expiratory
      flow, and mid-expiratory flow 25-75%; (c) analyses of beta2 microglobulin; blood
      styrene level; and urinary mandelic acid; and (d) cytogenetic study. The study
      results showed a statistically significant difference between the exposed and the
      control groups as regard the blood styrene level, urinary mandelic acid level,
      beta2 microgloblin in urine, and chromosomal study. The study also showed a
      statistically significant correlation between the duration of styrene exposure
      and ventilatory function parameters, also between the duration of styrene
      exposure and some detectable chromosomal aberrations. Our study recommends the
      implementation of preemployment and periodic medical examinations and health
      education programs using personal protective equipments and following the
      recommended allowable concentrations of styrene exposure.

PMID- 22609860
TI  - Modeling the kinetics of microbial degradation of deicing chemicals in porous
      media under flow conditions.
AB  - A quantitative knowledge of the fate of deicing chemicals in the subsurface can
      be provided by joint analysis of lab experiments with numerical simulation
      models. In the present study, published experimental data of microbial
      degradation of the deicing chemical propylene glycol (PG) under flow conditions
      in soil columns were simulated inversely to receive the parameters of
      degradation. We evaluated different scenarios of an advection-dispersion model
      including different terms for degradation, such as zero order, first order and
      inclusion of a growing and decaying biomass for their ability to explain the
      data. The general break-through behavior of propylene glycol in soil columns can
      be simulated well using a coupled model of solute transport and degradation with
      growth and decay of biomass. The susceptibility of the model to non-unique
      solutions was investigated using systematical forward and inverse simulations. We
      found that the model tends to equifinal solutions under certain conditions.

PMID- 22609861
TI  - Ionizing radiation-induced DNA damage response identified in marine mussels,
      Mytilus sp.
AB  - There is growing concern over the potential detrimental impact of ionizing
      radiation on natural biota. The mechanistic cause-and-effect impact of ionizing
      radiation has yet to be characterized in any aquatic species. Adopting an
      integrated approach, including radiochemical analysis of environmental samples,
      we evaluate molecular responses to ionizing radiation in the marine mussel,
      Mytilus edulis. These responses included analyses of RAD51 mRNA expression, a
      gene involved in the repair of DNA double strand breaks, and induction of DNA
      strand breaks using the comet assay, in samples collected from a site impacted by
      low level ionizing radiation discharges. Based on activities of the radionuclides
      measured in sediment and mussel tissue at the discharge site, external and
      internal dose rates were low, at ca. 0.61 MUGyh(-1) and significantly lower than
      the generic (all species) "no effect" dose rate of 10 uGyh(-1), yet DNA strand
      breakage and RAD51 mRNA expression were both altered.

PMID- 22609859
TI  - Structure of mammalian poly(ADP-ribose) glycohydrolase reveals a flexible
      tyrosine clasp as a substrate-binding element.
AB  - Reversible post-translational modification by poly(ADP-ribose) (PAR) regulates
      chromatin structure, DNA repair and cell fate in response to genotoxic stress.
      PAR glycohydrolase (PARG) removes PAR chains from poly ADP-ribosylated proteins
      to restore protein function and release oligo(ADP-ribose) chains to signal
      damage. Here we report crystal structures of mammalian PARG and its complex with
      a substrate mimic that reveal an open substrate-binding site and a unique
      'tyrosine clasp' enabling endoglycosidic cleavage of branched PAR chains.

PMID- 22609862
TI  - Effects of elevated carbon dioxide and nitrogen addition on foliar stoichiometry
      of nitrogen and phosphorus of five tree species in subtropical model forest
      ecosystems.
AB  - The effects of elevated carbon dioxide (CO2) and nitrogen (N) addition on foliar
      N and phosphorus (P) stoichiometry were investigated in five native tree species
      (four non-N2 fixers and one N2 fixer) in open-top chambers in southern China from
      2005 to 2009. The high foliar N:P ratios induced by high foliar N and low foliar
      P indicate that plants may be more limited by P than by N. The changes in foliar
      N:P ratios were largely determined by P dynamics rather than N under both
      elevated CO2 and N addition. Foliar N:P ratios in the non-N2 fixers showed some
      negative responses to elevated CO2, while N addition reduced foliar N:P ratios in
      the N2 fixer. The results suggest that N addition would facilitate the N2 fixer
      rather than the non-N2 fixers to regulate the stoichiometric balance under
      elevated CO2.

PMID- 22609863
TI  - Effect of different arbuscular mycorrhizal fungal isolates on growth and arsenic
      accumulation in Plantago lanceolata L.
AB  - The role of indigenous and non-indigenous arbuscular mycorrhizal fungi (AMF) on
      As uptake by Plantago lanceolata L. growing on substrate originating from mine
      waste rich in As was assessed in a pot experiment. P. lanceolata inoculated with
      AMF had higher shoot and root biomass and lower concentrations of As in roots
      than the non-inoculated plants. There were significant differences in As
      concentration and uptake between different AMF isolates. Inoculation with the
      indigenous isolate resulted in increased transfer of As from roots to shoots; AMF
      from non-polluted area apparently restricted plants from absorbing As to the
      tissue; and plants inoculated with an AMF isolate from Zn-Pb waste showed strong
      As retainment within the roots. Staining with dithizone indicated that AMF might
      be actively involved in As accumulation. The mycorrhizal colonization affected
      also the concentration of Cd and Zn in roots and Pb concentration, both in shoots
      and roots.

PMID- 22609864
TI  - Immunoassays distinguishing between HNL/NGAL released in urine from kidney
      epithelial cells and neutrophils.
AB  - BACKGROUND: The distinction between monomeric human neutrophil
      lipocalin/neutrophil gelatinase-associated lipocalin (HNL/NGAL), secreted by
      injured kidney tubular cells, and dimeric HNL/NGAL, released by activated
      neutrophils, is important to accurately diagnose acute kidney injury (AKI).
      METHODS: 132 urine samples from 44 intensive care unit (ICU) patients and five
      urine samples from non-ICU patients with urinary tract infections (UTIs) were
      analyzed by two monoclonal enzyme-linked immunosorbent assays (ELISA-1 and ELISA
      2). The presence of monomeric and/or dimeric HNL/NGAL in each sample was
      visualized by Western blotting. RESULTS: The ELISA-1 detected both monomeric and
      dimeric HNL/NGAL whereas the ELISA-2 almost exclusively detected dimeric HNL/NGAL
      with an area under the receiver-operating characteristics curve (AuROC) of 0.90.
      The ELISA-1/ELISA-2 ratio detected the monomeric form with an AuROC of 0.92. In
      32 AKI patients, dimer-specific ELISA-2 levels decreased pre-AKI whereas the
      monomer-specific ELISA-1/ELISA-2 ratio gradually increased beyond AKI diagnosis.
      High ELISA-2 levels and/or low ELISA-1/ELISA-2 ratios detected a predominance of
      dimeric HNL/NGAL in urine from the patients with UTIs. CONCLUSIONS: In
      combination, our two ELISAs distinguish monomeric HNL/NGAL, produced by the
      kidney epithelium, from dimeric HNL/NGAL, released by neutrophils during AKI
      development, as well as reduce the confounding effect of neutrophil involvement
      when bacteriuria is present.

PMID- 22609865
TI  - Control of the axial coordination of a surface-confined manganese (III) porphyrin
      complex.
AB  - The organization and thermal lability of chloro(5,10,15,20-tetraphenyl
      porphyrinato)manganese(III) (Cl-MnTPP) molecules on the Ag(111) surface have been
      investigated under ultra-high vacuum conditions, using scanning tunnelling
      microscopy, low energy electron diffraction and x-ray photoelectron spectroscopy.
      The findings reveal the epitaxial nature of the molecule-substrate interface, and
      moreover, offer a valuable insight into the latent coordination properties of
      surface-confined metalloporphyrins. The Cl-MnTPP molecules are found to self
      assemble on the Ag(111) surface at room temperature, forming an ordered molecular
      overlayer described by a square unit cell. In accordance with the threefold
      symmetry of the Ag(111) surface, three rotationally equivalent domains of the
      molecular overlayer are observed. The primitive lattice vectors of the Cl-MnTPP
      overlayer show an azimuthal rotation of +/-15 degrees  relative to those of the
      Ag(111) surface, while the principal molecular axes of the individual molecules
      are found to be aligned with the substrate (0(-)11) and ((-)211) crystallographic
      directions. The axial chloride (Cl) ligand is found to be orientated away from
      the Ag(111) surface, whereby the average plane of the porphyrin macrocycle lies
      parallel to that of the substrate. When adsorbed on the Ag(111) surface, the Cl
      MnTPP molecules display a latent thermal lability resulting in the dissociation
      of the axial Cl ligand at ~423 K. The thermally induced dissociation of the Cl
      ligand leaves the porphyrin complex otherwise intact, giving rise to the
      coordinatively unsaturated Mn(III) derivative. Consistent with the surface
      conformation of the Cl-MnTPP precursor, the resulting (5,10,15,20-tetraphenyl
      porphyrinato)manganese(III) (MnTPP) molecules display the same lattice structure
      and registry with the Ag(111) surface.

PMID- 22609866
TI  - Surface-structure-regulated penetration of nanoparticles across a cell membrane.
AB  - The cell uptake rate of nanoparticles (NPs) coated with mixed
      hydrophilic/hydrophobic ligands is known to be strongly influenced by the ligand
      pattern on the nanoparticle surface. To help reveal the physical mechanism behind
      this intriguing phenomenon, here we perform dissipative particle dynamics
      simulations to analyze the evolution of free energy as the ligand-coated NPs
      pierce through a lipid bilayer. Four characteristic ligand patterns are
      considered: striated NPs with alternating hydrophilic and hydrophobic groups
      compared to NPs with randomly mixed ligands at the same hydrophilic to
      hydrophobic ratio, as well as NPs coated with homogeneous hydrophilic or
      hydrophobic ligands. The free energy analysis indicates that among the four
      ligand patterns under study, the striated NP encounters the lowest energy barrier
      during translocation across the membrane. Further analysis reveals that the
      translocation of the striated NP is facilitated by the constraint of its
      rotational degree of freedom by the anisotropic ligand pattern, which prevented
      the free energy of the system from sinking to a deeper valley as the NP passes
      through the hydrophobic core of the bilayer. Finally, the critical forces
      required for almost instant penetration of these patterned NPs across the bilayer
      are calculated and shown to be consistent with the free energy analysis. These
      findings provide useful guidelines for the molecular design of patterned NPs for
      controllable cell penetrability.

PMID- 22609867
TI  - High-resolution ex vivo imaging in mouse spinal cord using micro-CT with 11.7T
      MRI and myelin staining validation.
AB  - We investigated the use of micro-CT with contrast agent for the characterization
      of fixed mouse spinal cord as a means to differentiate between gray and white
      matter. The spinal cords were soaked in a concentration of nonionic iodinated
      contrast agent for 14 days. Micro-CT was performed and then compared using 11.7T
      MRI images and myelin staining. Soaking the spinal cords in contrast agent
      resulted in clear differences in signal between the gray and white matter at 3
      planes. Micro-CT provides more relevant information on mouse spinal cord GM and
      WM anatomical structures.

PMID- 22609868
TI  - Aortic insufficiency due to ventricular septal defect (Laubry-Pezzi syndrome).
AB  - A 15-year-old boy showed progressive aortic valve regurgitation during follow-up
      of supracristal ventricular septal defect. This anatomic arrangement is
      consistent with the Laubry-Pezzi syndrome in which prolapse of a non-coronary
      aortic valve cusp due to Venturi's effect results in progressive aortic valve
      insufficiency.

PMID- 22609869
TI  - Focus on cardiac amyloidosis: a single-center experience with a long-term follow
      up.
AB  - AIM: Amyloidosis is a systemic disease, related to different underlying causes,
      with frequent cardiac involvement. Clinical evaluation, echocardiography and
      electrocardiography represent important noninvasive tools in identification of
      cardiac involvement. The aim of this study was to assess the clinical-laboratory
      features of a series of patients affected by cardiac amyloidosis in order to
      evaluate the risk of cardiac mortality. METHODS: We evaluated 48 patients (men
      65%, mean age 63 +/- 11 years) with biopsy-proven diagnosis of amyloidosis and
      heart involvement observed from 1991 to 2009. All patients underwent clinical
      laboratory evaluation at baseline and were followed up. RESULTS: During a median
      follow-up of 9.5 months (first to third interquartile: 3-41.5 months), 24
      patients (50%) died as a result of a cardiac cause. Survival free from cardiac
      death was 69, 50, 48 and 41% at 6, 12, 24 and 60 months from diagnosis,
      respectively. At multivariable Cox regression analysis, the presence of heart
      failure at enrolment [hazard ratio (HR) 4.67, 95% confidence interval (CI) 1.07
      20.27, P = 0.04] and history of recent syncope (HR 3.97, 95% CI 1.28-12.34, P =
      0.017) emerged as independent predictors of cardiac death. By using the equation
      derived from the multivariate analysis, individual survival probability at
      different times of follow-up was calculated. CONCLUSION: We confirm the
      particularly poor outcome of cardiac amyloidosis in the short term. A careful
      clinical evaluation emerges as the most important tool for the prognostic
      stratification and quantification of risk in patients with cardiac amyloidosis.

PMID- 22609870
TI  - Percutaneous closure of patent foramen ovale in a patient with situs viscerum
      inversus.
AB  - We describe the case of a patient with situs viscerum inversus totalis in whom we
      performed percutaneous closure of a patent foramen ovale. This case report may
      represent a further contribution to illustrate instrumental and interventional
      issues to consider in patients with situs viscerum inversus; it is also an
      example in which a background in embryology and congenital heart disease may aid
      cardiologists for the well-tolerated and effective diagnosis and treatment of
      adult patients with cardiac anomalies.

PMID- 22609871
TI  - Effects of atorvastatin on expression of ICAM-1 in atherosclerotic rabbits.
AB  - AIMS: Lipid accumulation and inflammatory response are major events in the
      progression of atherosclerosis. This research was performed to determine if
      atorvastatin could prevent atherosclerosis and its underlying mechanisms.
      METHODS: An atherosclerotic model was established in rabbits. Atorvastatin was
      administrated by gavage. Blood samples were collected to measure plasma total
      cholesterol, total triglyceride and low-density lipoprotein (LDL)-cholesterol.
      After the high-cholesterol diet with or without atorvastatin treatment, the
      morphological changes of the rabbits were examined with hematoxylin and eosin
      staining of tissues, and the expression of intercellular adhesion molecule 1
      (ICAM-1) was determined by immuno-staining and reverse transcriptase-PCR (RT
      PCR). RESULTS: Atorvastatin significantly reduced plasma levels of total
      cholesterol (41.7%) and LDL-cholesterol (34.6%). Neither the hypercholesterol
      diet nor atorvastatin treatment had any significant impact on body weight and
      plasma triglycerides. Treatment with atorvastatin significantly restored 40.9% of
      the widened intima and even down-regulated the ratio of intima/media by 55.5%.
      The inhibitory effects of atorvastatin on the expression of ICAM-1 showed a
      decrease of up to 37.6% (P < 0.01). The diseased rabbits showed a 167.3% increase
      in ICAM-1 mRNA expression (P < 0.01), which was reversed by nearly 46.4% by
      treatment with atorvastatin. CONCLUSION: Atorvastatin significantly prevents
      atherosclerotic changes in rabbits with a high-cholesterol diet, possibly by
      lowering plasma lipids and decreasing over-expressed ICAM-1.

PMID- 22609872
TI  - Targeting phosphatidylinositol 3-kinase-Akt through hepatocyte growth factor for
      cardioprotection.
AB  - Several growth factors have been shown to protect the cardiomyocyte from the
      detrimental effects of acute ischemia-reperfusion injury, through the activation
      of a variety of cell-surface receptors and the subsequent recruitment of a number
      of intracellular signal transduction pathways. Among these growth factors,
      hepatocyte growth factor (HGF), also named as scatter factor, acts by recruiting
      the phosphatidylinositol 3-kinase (PI3K)-Akt signal transduction pathway, linked
      to cardioprotection, at the time of myocardial infarction and myocardial
      reperfusion. HGF has been reported to increase in the early phase of myocardial
      infarction, and has been shown to have mitogenic, angiogenic, antiapoptotic and
      antifibrotic activities in cardiac myocytes and endothelial cells. Also,
      endogenous HGF may play an important role in the regeneration of endothelial
      cells and cardiomyocytes by promoting angiogenesis and inhibiting apoptosis
      during remodeling of the ischemic myocardium. Thus, HGF has the potential to
      emerge as a cardioprotective agent for the treatment of several pathological
      cardiac conditions. Here we review the role of HGF with respect to its ability to
      confer direct myocardial protection in the setting of ischemia-reperfusion
      injury, focusing on the main underlying signaling pathway involved.

PMID- 22609873
TI  - Protective mechanism of nicorandil on rat myocardial ischemia-reperfusion.
AB  - OBJECTIVES: To study the protective mechanism of nicorandil on myocardial
      ischemia-reperfusion injury. METHODS: Fifty rats were randomly divided into five
      groups, four of which were operated on to produce myocardial ischemia
      reperfusion. Nicorandil (5 mg/kg) was administrated by intravenous injection to
      three of the groups. The myocardial ultrastructure was observed by electron
      microscope. The expression levels of the antiapoptotic protein Bcl-2 and the pro
      apoptotic protein Bax were detected by immunohistochemical staining with
      rhodamine 123. The mitochondrial membrane potential was detected by
      spectrophotometry. RESULTS: The activity of lactate dehydrogenase (LDH) and
      malondialdehyde (MDA) content was decreased and the activity of superoxide
      dismutase (SOD) was increased in the three nicorandil groups, compared with those
      in the group without nicorandil (P < 0.01, P < 0.05). The positive staining level
      of the expressed Bcl-2 was increased and the expressed Bax was decreased (P <
      0.01) in the three nicorandil groups, compared with those in the group without
      nicorandil. The mitochondrial inner membrane potential was increased in the three
      nicorandil groups compared with that in the group without nicorandil (P < 0.05).
      CONCLUSION: A suitable level of nicorandil has a protective effect on rats'
      myocardial ischemia-reperfusion injury, and is mainly based on the opening of the
      mitochondrial KATP channel and the lowing of Ca overload.

PMID- 22609874
TI  - The role of cardiac surgery in adult patients with congenital heart disease.
AB  - The number of adults with congenital heart disease (CHD) has constantly increased
      as medical and surgical treatment of CHD - either simple or complex - continues
      to improve. Over the past half century, advances in surgical techniques have
      continued with the evolution of traditional surgical repair and introduction of
      new surgical procedures for complex lesions which were previously considered to
      be irreparable. We sought to analyze the current role of cardiac surgery in the
      treatment of congenital anomalies of the heart in those patients who have reached
      adulthood with or without surgical repair or palliation, with particular
      attention to future directions and perspectives. 

PMID- 22609875
TI  - Potent low toxicity inhibition of human melanogenesis by novel indole-containing
      octapeptides.
AB  - BACKGROUND: Abnormal production and accumulation of melanin are characteristics
      of a number of skin disorders, including postinflammatory hyperpigmentation and
      melasma. Our objective was to develop and validate novel oligopeptides with
      potent inhibitory activity against mushroom and human tyrosinase with minimal
      toxicity toward melanocytes, keratinocytes, and fibroblasts. METHODS: A library
      of short sequence oligopeptides was docked against the crystal structure of
      mushroom tyrosinase to screen for favorable binding free energies and direct
      interaction with the catalytic pocket. The inhibitory activity of the
      octapeptides and hydroquinone (HQ) was assessed using mushroom and human
      tyrosinase and melanin content via human primary melanocytes. Effects on cell
      viability and proliferation were determined using the MTT assay and cytotoxicity
      via trypan blue exclusion. RESULTS: Octapeptides P16-18 outperformed HQ, the
      benchmark of hypopigmenting agents, in all tested categories. Prolonged
      incubation of human keratinocytes, fibroblasts, or melanocytes with 30-3000MUM HQ
      led to 8- to 65-fold greater cell death than with octapeptides. After 6d of
      incubation with 30MUM HQ, we observed 70+/-3% and 60+/-2% cell death in
      melanocytes and fibroblasts, respectively, versus minimal toxicity up to an
      octapeptide concentration of 3mM. CONCLUSION: Octapeptides P16-18 are potent
      competitive tyrosinase inhibitors with minimal toxicity toward the major cell
      types of human skin. GENERAL SIGNIFICANCE: The findings in our study suggest that
      all three novel octapeptides may serve as safe and efficacious replacements of HQ
      for the treatment of pigmentary disorders.

PMID- 22609876
TI  - Polyunsaturated fatty acids cause apoptosis in C. albicans and C. dubliniensis
      biofilms.
AB  - BACKGROUND: Polyunsaturated fatty acids (PUFAs) have antifungal properties, but
      the mode by which they induce their action is not always clear. The aim of the
      study was to investigate apoptosis as a mode of action of antifungal PUFAs
      (stearidonic acid, eicosapentaenoic acid and docosapentaenoic acid) which are
      inhibitory towards biofilm formation of C. albicans and C. dubliniensis. METHODS:
      Candida biofilms were grown in the absence or presence of 1mM PUFAs (linoleic
      acid, stearidonic acid, eicosapentaenoic acid, docosapentaenoic acid) for 48h at
      37 degrees C. The effect of these PUFAs on the membrane fatty acid profile and
      unsaturation index, oxidative stress, mitochondrial transmembrane potential and
      apoptosis was evaluated. RESULTS: When biofilms of C. albicans and C.
      dubliniensis were exposed to certain PUFAs there was an increase in unsaturation
      index of the cellular membranes and accumulation of intracellular reactive oxygen
      species (ROS). This resulted in apoptosis, evidenced by reduced mitochondrial
      membrane potential and nuclear condensation and fragmentation. The most effective
      PUFA was stearidonic acid. CONCLUSIONS: The resultant cell death of both C.
      albicans and C. dubliniensis is due to apoptosis. GENERAL SIGNIFICANCE: Due to
      the increase in drug resistance, alternative antifungal drugs are needed. A group
      of natural antifungal compounds is PUFAs. However, understanding their mechanisms
      of action is important for further use and development of these compounds as
      antifungal drugs. This paper provides insight into a possible mode of action of
      antifungal PUFAs.

PMID- 22609877
TI  - Sulfate uptake in photosynthetic Euglena gracilis. Mechanisms of regulation and
      contribution to cysteine homeostasis.
AB  - BACKGROUND: Sulfate uptake was analyzed in photosynthetic Euglena gracilis grown
      in sulfate sufficient or sulfate deficient media, or under Cd(2+) exposure or Cys
      overload, to determine its regulatory mechanisms and contribution to Cys
      homeostasis. RESULTS: In control and sulfate deficient or Cd(2+)-stressed cells,
      one high affinity and two low affinity sulfate transporters were revealed, which
      were partially inhibited by photophosphorylation and oxidative phosphorylation
      inhibitors and ionophores, as well as by chromate and molybdate; H(+) efflux also
      diminished in presence of sulfate. In both sulfate deficient and Cd(2+)-exposed
      cells, the activity of the sulfate transporters was significantly increased.
      However, the content of thiol-metabolites was lower in sulfate-deficient cells,
      and higher in Cd(2+)-exposed cells, in comparison to control cells. In cells
      incubated with external Cys, sulfate uptake was strongly inhibited correlating
      with 5-times increased intracellular Cys. Re-supply of sulfate to sulfate
      deficient cells increased the Cys, gamma-glutamylcysteine and GSH pools, and to
      Cys-overloaded cells resulted in the consumption of previously accumulated Cys.
      In contrast, in Cd(2+) exposed cells none of the already elevated thiol
      metabolites changed. CONCLUSIONS: (i) Sulfate transport is an energy-dependent
      process; (ii) sulfate transporters are over-expressed under sulfate deficiency or
      Cd(2+) stress and their activity can be inhibited by high internal Cys; and (iii)
      sulfate uptake exerts homeostatic control of the Cys pool.

PMID- 22609878
TI  - Treatment options for malignant pleural effusions: patient preference does
      matter.

PMID- 22609879
TI  - Higher endogenous nitrite levels are associated with superior exercise capacity
      in highly trained athletes.
AB  - Factors improving exercise capacity in highly trained individuals are of major
      interest. Recent studies suggest that the dietary intake of inorganic nitrate may
      enhance athletic performance. This has been related to the stepwise in vivo
      bioactivation of nitrate to nitrite and nitric oxide (NO) with the modulation of
      mitochondrial function. Here we show that higher baseline levels of nitrite are
      associated with a superior exercise capacity in highly trained athletes
      independent of endothelial function. Eleven male athletes were enrolled in this
      investigation and each participant reported twice to the testing facility (total
      of n=22 observations). Venous blood was obtained to determine the levels of
      circulating plasma nitrite and nitrate. Endothelial function was assessed by
      measuring flow-mediated vasodilation (FMD). Hereafter, participants completed a
      stepwise bicycle exercise test until exhaustion. Blood was drawn from the ear
      lope to determine the levels of lactate. Lactate anaerobic thresholds (LAT) in
      relation to heart rate were calculated using non-linear regression models.
      Baseline plasma nitrite levels correlated with LATs (r=0.65; p=0.001, n=22) and
      with endothelial function as assessed by FMD (r=0.71; p=0.0002). Correlation
      coefficients from both testing days did not differ. Multiple linear regressions
      showed that baseline plasma nitrite level but not endothelial function was an
      independent predictor of exercise capacity. No such correlations were determined
      for plasma nitrate levels.

PMID- 22609880
TI  - Irradiated allogeneic cells enhance umbilical cord blood stem cell engraftment in
      immunodeficient mice.
AB  - Umbilical cord blood (UCB) is a readily available source of hematopoietic stem
      cells for transplantation. UCB hematopoietic SCT for average- and large-sized
      patients is often limited by the number of cells available in a single unit. To
      address this limitation, we performed experiments to determine if adjunctive
      therapy with third-party human allogeneic cells enhances the engraftment of human
      UCB in immunodeficient mice. UCB cells with or without sequential infusion of
      irradiated third-party allogeneic cells were used in transplantation studies of
      NOD/SCID and NOD/SCID-IL2Rgamma null mice. We studied the impact of irradiated
      allogeneic cells on colony formation in vitro using long-term culture assays
      also. Our studies demonstrate that short- and long-term UCB engraftment of
      immunodeficient mice is enhanced by irradiated allogeneic cells. Secondary
      transplants demonstrate the durability of engraftment. These preclinical studies
      support the further development of irradiated allogeneic cells as an adjunct to
      single UCB transplantation when limiting numbers of cells are available.

PMID- 22609881
TI  - Extensive chronic GVHD is associated with donor blood CD34+ cell count after G
      CSF mobilization in non-myeloablative allogeneic PBSC transplantation.
AB  - The correlation between the incidence of GVHD and the number of infused CD34(+)
      cells remains controversial for PBSC transplantation after a reduced-intensity
      conditioning (RIC) regimen. We evaluated 99 patients transplanted with an HLA
      identical sibling after the same RIC (2-Gy-TBI/fludarabine). Donor and recipient
      characteristics, donor's blood G-CSF-mobilized CD34(+) cell count, and number of
      infused CD34(+) and CD3(+) cells were analyzed as risk factors for acute and
      chronic GVHD There was a trend for an increased incidence of extensive chronic
      GVHD in the quartile of patients receiving more than 10 * 10(6) CD34(+) cells/kg
      (P = 0.05). Interestingly, the number of donor's blood CD34(+) cells at day 5 of
      G-CSF mobilization was closely associated with the incidence of extensive chronic
      GVHD, that is, 48% (95% CI: 28-68) at 24-months in the quartile of patients whose
      donors had the highest CD34(+) cell counts versus 24.3% (95% CI: 14-34) in the
      other patients (P = 0.007). In multivariate analysis, the only factor correlating
      with extensive chronic GVHD (cGVHD) was the donor's blood CD34(+) cell count
      after G-CSF (HR 2.49; 95% CI: 1.16-5.35, P = 0.019). This study shows that the
      incidence of cGVHD is more strongly associated with the donor's ability to
      mobilize CD34(+) cells than with the number of infused CD34(+) cells.

PMID- 22609882
TI  - Personality influences quality-of-life assessments in adult patients after
      allogeneic hematopoietic SCT: results from a joint evaluation of the prospective
      German Multicenter Validation Trial and the Fred Hutchinson Cancer Research
      Center.
AB  - The influence of personality on health related quality of life (QoL) and physical
      functioning in the setting of allogeneic hematopoietic SCT (alloHSCT) is unknown.
      We conducted a joint evaluation within two independent cohorts of alloHSCT
      recipients to investigate the impact of personality on reported QoL and physical
      functioning. Two-hundred-eight patients (median age 44 years, range 18-72) of
      cohort 1 and 93 patients (median age 55 years, range 19-79) of cohort 2 after
      alloHSCT were evaluated. Personality was assessed using the 24-adjective measure
      (AM), which measures the Big-Five personality domains and the Life Orientation
      Test-Revised (LOT-R), measuring optimism and pessimism. QoL was measured using
      the Functional Assessment of Cancer Therapy with bone marrow transplantation
      subscale (FACT-BMT), Short Form 36 (SF-36), the human activity profile (HAP), as
      well as the NIH criteria-based cGVHD activity assessment form and the Lee cGVHD
      symptom scale. Neuroticism was significantly associated with worse function
      measured by the HAP and FACT-BMT. Optimism significantly improved QoL captured by
      the FACT-BMT. Pessimism significantly impaired physical function captured by the
      HAP and SF-36. Extraversion was significantly associated with reduced depression
      and lower severity of cGVHD symptoms reported by the patient and the physician.
      The results suggest that personality traits and pre-treatment QoL assessments
      should be measured in clinical trials to facilitate the interpretation of QoL
      data.

PMID- 22609883
TI  - Consolidation of first-line therapy with busulphan and melphalan, and autologous
      stem cell rescue in children with Ewing's sarcoma.
AB  - According to the published report on current practice of hematopoietic SCT in
      Europe, high-dose therapy (HDT) with autologous stem cell support is a standard
      of care in paediatric patients with high risk (HR) or relapsed Ewing's sarcoma
      (ES). Randomized trials, however, have not confirmed the value of this procedure
      yet. In this retrospective analysis we intended to evaluate the role of HDT as a
      consolidation therapy in first remission of ES. A total of 102 patients were
      included in the analysis and divided according to the following risk factors:
      metastatic disease at presentation, feasibility of surgery and histological
      response after induction. Forty-one patients were classified as standard risk
      (SR) patients, while the remaining 61 children, with at least one risk factor,
      were classified as HR patients. HR group patients were non-randomized and
      qualified according to the decision of the local clinician to give a conventional
      consolidation (CC) or to perform high-dose chemotherapy and radiotherapy in
      selected patients. Twenty-six children were given CC while 35 patients were
      treated with HDT. The HDT consisted of oral BU 4 mg/kg p.o. in divided doses
      daily for 4 days (total dose 16 mg/kg) followed by melphalan 140 mg/m(2) i.v. on
      day -2. Probability of relapse-free survival (RFS) in median observation time was
      significantly worse in HR patients who were given CC therapy as compared with
      children with HR features receiving high-dose chemotherapy (0.27 vs 0.66 (P =
      0.008); OS 0.31 vs 0.71 (P = 0.007), respectively). Patients from the SR group
      had a probability of RFS of 0.72 and OS of 0.75, and the difference between SR
      and HR patients after HDT was NS (P = 0.37). Our observation confirms that the
      consolidation of the first-line treatment with BU and melphalan improves the
      outcome in ES patients with HR features.

PMID- 22609884
TI  - Mobilization of PBSCs in poor mobilizers with POEMS syndrome using G-CSF with
      plerixafor.

PMID- 22609886
TI  - Folinic acid administration after MTX GVHD prophylaxis in pediatric allo-SCT.
AB  - Cyclosporine (CsA) and MTX are commonly used for GVHD prophylaxis in pediatric
      allo-SCT. Mucositis and hepatic toxicity frequently restrict the delivery of the
      fourth dose of MTX. Folinic acid (FA) may ameliorate MTX toxicity. We conducted a
      retrospective chart review of all pediatric patients who received CsA and MTX for
      GVHD prophylaxis from January 2000 to July 2010. Patients treated before July
      2007 (N=29) did not receive FA and those treated from July 2007 onward did
      receive FA (N=18). Patients who received FA were significantly more likely to
      receive day +11 MTX (odds ratio (OR) 10.42, 95% confidence interval (CI): 1.21
      262.27) but there was no significant difference in Grade III-IV GVHD between the
      two groups (OR 1.15, 95% CI: 0.08-18.14). FA did not impact relapse-free survival
      (RFS) (P=0.82). Increased likelihood of receiving day +11 MTX suggests that FA
      ameliorates MTX toxicity, such as severe mucositis. FA administration for MTX
      GVHD prophylaxis should be studied in a prospective, randomized fashion.

PMID- 22609885
TI  - Pre-transplantation iron chelation in patients with MDS or acute leukemia and
      iron overload undergoing myeloablative allo-SCT.

PMID- 22609887
TI  - Determining Toxoplasma high-risk autologous and allogeneic hematopoietic stem
      cell transplantation patients by systematic pre-transplant PCR screening of stem
      cell originated buffy coat.
AB  - The diagnosis of Toxoplasma infection or disease in hematopoietic stem cell
      transplantation (HSCT) patients is achieved mainly by PCR screening; however
      screening did not find wide field of use in practice due to costly expenditures
      of PCR. This study aimed to determine patients at high risk of Toxoplasma
      infection or disease before transplantation by stem cell originated buffy coat
      PCR and subsequently to screen them. Buffy coats collected from 12 autologous and
      18 allogeneic HSCT patients' donors were investigated by PCR before
      transplantation. After transplantation, blood and sera collected at fixed time
      intervals were screened by two PCR methods and serological assays. Screening
      results first time assessed a toxoplasmosis incidence level as 25% in autologous
      HSCT patients and increased incidence level in allogeneic HSCT patients to 22%.
      Importantly, buffy coat PCR was first time performed before transplantation, to
      determine the risk of toxoplasmosis. Buffy coat PCR results showed that four
      patients were at high risk of toxoplasmosis before transplantation. After
      transplantation, these patients experienced toxoplasmosis. In conclusion, for the
      determination of patients at risk of toxoplasmosis, clinicians should consider
      buffy coat PCR in combination with serology before transplantation. After
      transplantation, PCR screening can be initiated in high risk patients upon
      clinical suspicion.

PMID- 22609888
TI  - Specific detection of all members of the Venezuelan Equine Encephalitis complex:
      development of a RT-Nested PCR.
AB  - Venezuelan Equine Encephalitis (VEE) complex belongs to alphavirus genus in the
      family Togaviridae. Several species of this complex are pathogenic to humans. VEE
      infections can produce severe or mild disease, and many cases remain undiagnosed.
      A specific and sensitive reverse transcriptase nested polymerase chain reaction
      (RT-Nested PCR) method was developed for the detection of all VEE subtypes,
      including Rio Negro Virus (RNV) (subtype VI), which circulates only in Argentina.
      Degenerated primers were designed and thermal cycling parameters were
      standardized. This technique is suitable for rapid and specific detection of
      these viruses, and may be useful for diagnosis and surveillance.

PMID- 22609889
TI  - Large-scale comparison of Roche Cobas AmpliPrep/Cobas TaqMan and Abbott RealTime
      HIV assays.
AB  - Significant underquantitation of HIV RNA has been reported with the Roche Cobas
      AmpliPrep/Cobas TaqMan HIV Test (Version 1) compared to other assays. However,
      these studies have generally involved limited numbers of samples from select
      patient populations or analysis of samples that were undetectable in the TaqMan
      assay. Random plasma samples submitted from throughout the United States for HIV
      RNA quantitation (n=1263) were compared in the Roche TaqMan and Abbott RealTime
      assays. Twenty-four samples (1.9%) were discrepant, with a maximum difference
      between the two assays of 1.9logcopies/mL. These data indicate that both tests
      may be susceptible to underquantitation, but the incidence is low in this large
      cohort of samples from across the United States.

PMID- 22609890
TI  - Development of a real-time RT-PCR assay with TaqMan probe for specific detection
      of acute bee paralysis virus.
AB  - Real-time polymerase chain reaction (real-time PCR) is an accurate, rapid and
      reliable method that can be used for the detection and also for the quantitation
      of specific DNA molecules. It can be non-specific, with intercalating dyes (SYBR
      Green I dye) able to bind to any dsDNA, or specific with a probe (TaqMan),
      whereby the probe is designed to bind within the amplified PCR fragment. A new
      real-time reverse transcription and polymerase chain reaction (real time RT-PCR)
      assay with TaqMan probe for specific detection of acute bee paralysis virus was
      designed. The assay was optimized to be highly sensitive and analytically
      specific and tested with a selection of genetically diverse ABPV strains
      originating from Slovenia, the United Kingdom (UK), Hungary and Germany. The
      detection limit of the assay and sensitivity comparisons with conventional RT-PCR
      were analyzed and this assay can detect a minimum of 44 copies of ABPV/reaction
      and is 230 times more sensitive than conventional RT-PCR. In addition, the assay
      is highly reproducible, with an average slope of standard curve made of ten-fold
      dilutions of standard copies/reaction -3.479+/-0.19 and an average slope of
      standard curve made of ten-fold dilutions of RNA -3.409+/-0.18.

PMID- 22609892
TI  - Calcium and bone.
AB  - OBJECTIVE: Evaluate the role of calcium on bone health. METHODS: Review of
      literatures on calcium and bone development during childhood and bone health in
      adulthood and older age. RESULTS: Calcium intake influences skeletal calcium
      retention during growth and thus affects peak bone mass achieved in early
      adulthood. Increased calcium intake is associated with increased bone mineral
      accretion rate up to a threshold level in all ethnic groups. The minimum intake
      to achieve maximal retention is 1140 mg/day for white boys and 1300 mg/day for
      white girls. Calcium also plays a role in preventing bone loss and osteoporotic
      fractures in later life. Meta-analyses report that calcium supplementation reduce
      bone loss by 0.5-1.2% and the risk of fracture of all types by at least 10% in
      older people. Low calcium intake is a widespread problem across countries and age
      groups. CONCLUSION: Adequate calcium intake throughout lifetime is important for
      bone health and the prevention of osteoporosis and related fractures.

PMID- 22609893
TI  - Determination of calprotectin in gingival crevicular fluid by immunoassay on a
      microchip.
AB  - OBJECTIVES: Gingival crevicular fluid (GCF) contains calprotectin, which appears
      to be a useful biomarker for periodontal diseases because of its high level in
      GCF from periodontally diseased pockets. To determine calprotectin in GCF that
      has a very small volume, sandwich enzyme-linked immunosorbent assay (ELISA) on a
      microchip was performed and its utility was estimated. DESIGN AND METHODS: Anti
      calprotectin primary antibody was discharged on a microchip using a piezoelectric
      inkjet printing system. Calprotectin standard and calprotectin in GCF samples
      from eleven subjects were determined by the ELISA method with the prepared
      microchip and their values were compared with those obtained by conventional
      ELISA. RESULTS: Using the ELISA on a microchip, a reasonable standard curve of
      calprotectin protein (1.56-100 ng/mL) was obtained. Calprotectin in GCF samples
      was quantified and showed reasonable values in accordance with the condition of
      periodontal diseases. The values determined by the microchip method and
      conventional ELISA showed a significant linear relationship (R(2)=0.981).
      CONCLUSIONS: Calprotectin in GCF was determined using the ELISA on a microchip
      with high efficiency and this ELISA method for calprotectin determination may
      become a useful method for diagnosing periodontal diseases.

PMID- 22609894
TI  - Soluble TNFalpha receptor type I and hepcidin as determinants of development of
      anemia in the long-term follow-up of heart failure patients.
AB  - BACKGROUND: Anemia is common in patients with chronic heart failure (CHF) and is
      associated with a worse prognosis. This study aims to identify the biological
      mechanisms which reflect evolutionary changes in the hemoglobin concentrations in
      heart failure patients who are still not anaemic. METHODS: Fifty-nine patients
      (54 +/- 14 years, 83% males) with CHF (LVEF 28 +/- 10%), who did not have anemia,
      and had not received any previous transfusions, were included. The parameters
      studied were: iron metabolism (ferritin, iron, transferrin, soluble transferrin
      receptor (sTfR), hepcidin); inflammation (C-reactive protein, soluble TNFalpha
      receptor I (sTNFRI), interleukin 6); and myocardial stress (NT-proBNP, high
      sensitivity TnT, growth differentiation factor 15). All parameters were measured
      on inclusion and 1 year after inclusion. RESULTS: Baseline hemoglobin (g/dL) was
      14.7 +/- 1.5 and at 1 year of follow-up it showed a significant decrease of -0.4
      (RIC: -0.7 to -0.06) (p=0.02). At baseline, only the sTNFRI was a predictor of a
      decrease in hemoglobin 1 year later (p=0.007). During follow-up, the increase in
      sTNFRI (p=0.002, r=-0.39) and hepcidin (p=0.006, r=-0.35) were both associated
      with a decrease in hemoglobin. Similarly, the patients who became anemic (13%)
      had higher levels of hepcidin (p=0.001) and sTNFRI (p=0.008). The remaining
      parameters did not show any relationship with the evolution in the hemoglobin.
      CONCLUSIONS: In CHF patients without anemia, the increase in the inflammatory
      state (sTNFRI) and the following deterioration in the iron metabolism (hepcidin)
      were the main determinants of a decrease in hemoglobin and the appearance of
      anemia in the long term follow-up period.

PMID- 22609896
TI  - NTproBNP concentrations in healthy children.
AB  - INTRODUCTION: There have been limited studies generating BNP and NT-proBNP
      reference intervals for paediatric populations. We prospectively assessed NT
      proBNP levels in a cohort of 854 healthy school children from the Lifestyle of
      Our Kids (LOOK) prospective longitudinal study. MATERIALS AND METHODS: NT-proBNP
      analysis was performed on 172 girls and 212 boys with average age 8.1 years, 183
      girls and 181 boys, average age 10.1 years and 183 girls and 180 boys with
      average age 11.9 years. Data were stratified according to age and gender with the
      median, range of results and 2.5th and 97.5th percentiles calculated RESULTS:
      There were no significant differences between males and females at any of the 3
      study ages. Significant differences were seen between the 8 and 12 year-olds, 10
      and 12 year-olds and the 8 and 12 year-old boys. DISCUSSION: Our study
      demonstrated that NT-proBNP concentrations in healthy children progressively
      decline between ages 8 and 12 years. Our selection of unambiguously healthy
      children produced similar median but lower 97.5th percentile NT-proBNP
      concentrations to previously published studies.

PMID- 22609891
TI  - Relation between pulmonary function and 10-year risk for cardiovascular disease
      among healthy men and women in Italy: the Moli-sani Project.
AB  - BACKGROUND: Pulmonary dysfunction could influence the onset and the evolution of
      cardiovascular disorders. This study evaluated whether pulmonary dysfunction
      based on spirometry, plethysmography and carbon monoxide diffusion test is
      associated with the estimated risk of cardiovascular disease in 10 years. DESIGN:
      We performed a cross-sectional general population-based cohort study. METHODS:
      The Moli-sani Project is a population-based cohort study of subjects aged >=35
      years, randomly recruited from the general population in Italy. Cardiovascular
      risk in 10 years was predicted by the CUORE score which provides an estimate of
      the probability of a first coronary or cerebrovascular event in the next 10
      years, based on a risk equation derived from Italian cohorts. Out of 12,933
      subjects with high-quality flow/volume manoeuvre, 8,132 subjects had suitable
      plethysmography and 3,422 carbon monoxide diffusion (carbon monoxide alveolar
      diffusion test [DLCO]). RESULTS: In multivariate analyses, reduced pulmonary
      function expressed by forced vital capacity (FVC), forced expiratory volume in
      the first second (FEV1) and total lung capacity (TLC) were inversely associated
      with CUORE score both in men and in women, independently of other risk factors
      such as age, height, smoking habits, total cigarettes exposure (pack-years),
      pulmonary disease, body mass index, social status and physical activity. In
      contrast, there was no association between FEV1/FVC ratio, residual volume, DLCO
      and CUORE risk score. CONCLUSIONS: In both genders from an adult general Italian
      population, pulmonary function decline is associated with increased
      cardiovascular risk. These results suggest that pulmonary monitoring could be
      useful to more accurately predict cardiovascular risk.

PMID- 22609895
TI  - Diagnostic utility of a single-epitope sandwich B-type natriuretic peptide assay
      in stable coronary artery disease: data from the Akershus Cardiac Examination
      (ACE) 1 Study.
AB  - OBJECTIVES: To assess the merit of a novel single-epitope sandwich (SES) assay
      specific to the stable part of BNP in patients with reversible myocardial
      ischemia as post-translational modifications of BNP may influence assay
      performance. DESIGN AND METHODS: We measured BNP concentration by a conventional
      assay and the SES-BNP assay in 198 patients referred for myocardial perfusion
      imaging (MPI). BNP concentration was determined before and immediately after
      exercise stress testing, and 1.5 and 4.5h later. Patients were categorized
      according to MPI results. RESULTS: BNP concentration was higher with both assays
      at all time points in patients with reversible myocardial ischemia (n=19)
      compared to the other patients (n=179). Measuring BNP after stress testing or
      calculating the changes in BNP concentration did not improve diagnostic accuracy
      compared to baseline measurements: SES-BNP: AUC 0.71 (95% CI 0.58-0.84) vs.
      conventional BNP: 0.71 (0.59-0.83), p=0.96. By linear regression analysis,
      reversible myocardial ischemia was significantly associated with baseline SES-BNP
      concentration (p=0.043), but not with measurements by the conventional assay
      (p=0.089). In multivariate logistic regression models, only baseline measurement
      with the SES-BNP assay was significantly associated with reversible myocardial
      ischemia: odds ratio [logarithmical transformed BNP] 2.00 (95% CI 1.16-3.47),
      p=0.013. The SES-BNP assay, but not the conventional BNP assay, reclassified a
      significant proportion of the patients towards their correct category on top of
      the best clinical model of our data set: NRI=0.47, p=0.04. CONCLUSIONS: The SES
      BNP assay was significantly associated with reversible myocardial ischemia as
      assessed by several statistical indices, while a conventional BNP assay was not.

PMID- 22609897
TI  - Analytical evaluation of Sysmex UF-1000i for flow cytometric analysis of
      peritoneal fluid.
AB  - OBJECTIVE: To evaluate analytical performance of Sysmex UF-1000i for peritoneal
      fluid analysis. METHODS: Functional sensitivity, imprecision, linearity and
      comparison studies were performed on peritoneal fluids. RESULTS: Total
      imprecision was 1.6-4.7%, functional sensitivity 27/MUL for white blood cell
      (WBC) and 32/MUL for total nucleated cell (TNC) count. Linearity was excellent up
      to 983 cell/MUL, carry-over <0.2%, correlation with manual microscopy always
      greater than 0.992. CONCLUSION: The instrument exhibited optimal performance at
      the conventional WBC diagnostic thresholds.

PMID- 22609898
TI  - An advanced fabrication method of highly ordered ZnO nanowire arrays on silicon
      substrates by atomic layer deposition.
AB  - In this work, the controlled fabrication of highly ordered ZnO nanowire (NW)
      arrays on silicon substrates is reported. Si NWs fabricated by a combination of
      phase shift lithography and etching are used as a template and are subsequently
      substituted by ZnO NWs with a dry-etching technique and atomic layer deposition.
      This fabrication technique allows the vertical ZnO NWs to be fabricated on 4 in
      Si wafers. Room temperature photoluminescence and micro-photoluminescence are
      used to observe the optical properties of the atomic layer deposition (ALD) based
      ZnO NWs. The sharp UV luminescence observed from the ALD ZnO NWs is unexpected
      for the polycrystalline nanostructure. Surprisingly, the defect related
      luminescence is much decreased compared to an ALD ZnO film deposited at the same
      time ona plane substrate. Electrical characterization was carried out by using
      nanomanipulators. With the p-type Si substrate and the n-type ZnO NWs the
      nanodevices represent p-n NW diodes.The nanowire diodes show a very high
      breakthrough potential which implies that the ALD ZnO NWs can be used for future
      electronic applications.

PMID- 22609900
TI  - Ligand effects on the stability of thiol-stabilized gold nanoclusters:
      Au25(SR)18(-), Au38(SR)24, and Au102(SR)44.
AB  - We have studied the electrochemical and thermodynamic stability of
      Au(25)(SR)(18)(-), Au(38)(SR)(24), and Au(102)(SR)(44), R = CH(3), C(6)H(13),
      CH(2)CH(2)Ph, Ph, PhF, and PhCOOH, in order to examine ligand effects on the
      stability of thiol-stabilized gold nanoclusters, Au(m)(SR)(n). Aliphatic thiols,
      in general, have higher electrochemical and thermodynamic stability than aromatic
      thiols, and the -SCH(2)CH(2)Ph thiol is particularly appealing because of its
      high electrochemical and thermodynamic stability. The stabilization of Au(m) by
      nSR for Au(m)(SR)(n) can be rationalized by the stabilization of an Au atom by an
      SR for the simple molecule AuSR, regardless of interligand interaction and system
      size and shape. Thiol moieties play a strong role in the electron oxidation and
      reduction of Au(m)(SR)(n). Accounting for the characteristics of thiol ligands is
      essential for understanding the electronic and thermodynamic stability of thiol
      stabilized gold nanoclusters.

PMID- 22609899
TI  - The temporal lag structure of short-term associations of fine particulate matter
      chemical constituents and cardiovascular and respiratory hospitalizations.
AB  - BACKGROUND: In air pollution time-series studies, the temporal pattern of the
      association of fine particulate matter (PM2.5; particulate matter <= 2.5 um in
      aerodynamic diameter) and health end points has been observed to vary by disease
      category. The lag pattern of PM2.5 chemical constituents has not been well
      investigated, largely because daily data have not been available. OBJECTIVES: We
      explored the lag structure for hospital admissions using daily PM2.5 chemical
      constituent data for 5 years in the Denver Aerosol Sources and Health (DASH)
      study. METHODS: We measured PM2.5 constituents, including elemental carbon,
      organic carbon, sulfate, and nitrate, at a central residential site from 2003
      through 2007 and linked these daily pollution data to daily hospital admission
      counts in the five-county Denver metropolitan area. Total hospital admissions and
      subcategories of respiratory and cardiovascular admissions were examined. We
      assessed the lag structure of relative risks (RRs) of hospital admissions for
      PM2.5 and four constituents on the same day and from 1 to 14 previous days from a
      constrained distributed lag model; we adjusted for temperature, humidity, longer
      term temporal trends, and day of week using a generalized additive model.
      RESULTS: RRs were generally larger at shorter lags for total cardiovascular
      admissions but at longer lags for total respiratory admissions. The delayed lag
      pattern was particularly prominent for asthma. Elemental and organic carbon
      generally showed more immediate patterns, whereas sulfate and nitrate showed
      delayed patterns. CONCLUSION: In general, PM2.5 chemical constituents were found
      to have more immediate estimated effects on cardiovascular diseases and more
      delayed estimated effects on respiratory diseases, depending somewhat on the
      constituent.

PMID- 22609901
TI  - Disentangling the contributions of grasp and action representations in the
      recognition of manipulable objects.
AB  - There is an increasing evidence that the action properties of manipulable objects
      can play a role in object recognition, as objects with similar action properties
      can facilitate each other's recognition [Helbig et al. Exp Brain Res 174:221-228,
      2006]. However, it is unclear whether this modulation is driven by the actions
      involved in using the object or the grasps afforded by the objects, because these
      factors have been confounded in previous studies. Here, we attempted to
      disentangle the relative contributions of the action and grasp properties by
      using a priming paradigm in which action and grasp similarity between two objects
      were varied orthogonally. We found that target tools with similar grasp
      properties to the prime tool were named more accurately than those with
      dissimilar grasps. However, naming accuracy was not affected by the similarity of
      action properties between the prime and target tools. This suggests that
      knowledge about how an object is used is not automatically accessed when
      identifying a manipulable object. What are automatically accessed are the
      transformations necessary to interact directly with the object--i.e., the manner
      in which one grasps the object.

PMID- 22609903
TI  - Translational bioinformatics: data-driven drug discovery and development.
AB  - Internet-accessible computing power and data-sharing mandates now enable
      researchers to interrogate thousands of publicly available databases containing
      molecular, clinical, and epidemiological data. With emerging new approaches,
      translational bioinformatics can now provide answers to previously untouchable
      questions, ranging from detecting population signals of adverse drug reactions to
      clinical interpretation of the whole genome. There are challenges, including lack
      of access to some data sources and software, but there are also overwhelming
      doses of hopes and expectations.

PMID- 22609906
TI  - Drug research and translational bioinformatics.

PMID- 22609907
TI  - Needs for an expanded ontology-based classification of adverse drug reactions and
      related mechanisms.
AB  - The growing significance of bioinformatics and systems biology in drug safety
      research requires a system of adverse-event classification that goes beyond a
      simple vocabulary. This opinion piece outlines the need for development of an
      ontology-based framework of describing adverse drug reactions (ADRs) and
      describes the potential applications for such a framework.

PMID- 22609908
TI  - Healthy volunteer registries and ethical research principles.
AB  - The dual enrolling of phase I volunteers is a potential risk to subjects. It can
      also distort study results, threaten study validity, and possibly cause harm to
      future patients. Existing subject registries differ in structure, funding, and
      governance. Although the choice of the ideal system is driven by the scope of the
      risk and the funding mechanism, and is ultimately a value judgment of freedom
      versus paternalism, none of the registries significantly impinges on the tenets
      of ethically based research.

PMID- 22609909
TI  - The perils of gene patents.
AB  - I argue here that gene patents, and patented genetic tests based on them, are a
      very bad idea. First, I discuss whether genes can reasonably be the subject of
      patents in the first place; I maintain that the answer is no. Second, I explain
      how gene patents interfere with scientific progress, slowing down the development
      of new cures and treatments for genetic diseases.

PMID- 22609911
TI  - Functional analyses of mycobacterial lipoprotein diacylglyceryl transferase and
      comparative secretome analysis of a mycobacterial lgt mutant.
AB  - Preprolipopoprotein diacylglyceryl transferase (Lgt) is the gating enzyme of
      lipoprotein biosynthesis, and it attaches a lipid structure to the N-terminal
      part of preprolipoproteins. Using Lgt from Escherichia coli in a BLASTp search,
      we identified the corresponding Lgt homologue in Mycobacterium tuberculosis and
      two homologous (MSMEG_3222 and MSMEG_5408) Lgt in Mycobacterium smegmatis. M.
      tuberculosis lgt was shown to be essential, but an M. smegmatis DeltaMSMEG_3222
      mutant could be generated. Using Triton X-114 phase separation and
      [(14)C]palmitic acid incorporation, we demonstrate that MSMEG_3222 is the major
      Lgt in M. smegmatis. Recombinant M. tuberculosis lipoproteins Mpt83 and LppX are
      shown to be localized in the cell envelope of parental M. smegmatis but were
      absent from the cell membrane and cell wall in the M. smegmatis DeltaMSMEG_3222
      strain. In a proteomic study, 106 proteins were identified and quantified in the
      secretome of wild-type M. smegmatis, including 20 lipoproteins. All lipoproteins
      were secreted at higher levels in the DeltaMSMEG_3222 mutant. We identify the
      major Lgt in M. smegmatis, show that lipoproteins lacking the lipid anchor are
      secreted into the culture filtrate, and demonstrate that M. tuberculosis lgt is
      essential and thus a validated drug target.

PMID- 22609913
TI  - Development of competence for genetic transformation of Streptococcus mutans in a
      chemically defined medium.
AB  - Streptococcus mutans develops competence for genetic transformation in response
      to regulatory circuits that sense at least two peptide pheromones. One peptide,
      known as CSP, is sensed by a two-component signal transduction system through a
      membrane receptor, ComD. The other, derived from the primary translation product
      ComS, is thought to be sensed by an intracellular receptor, ComR, after uptake by
      oligopeptide permease. To allow study of this process in a medium that does not
      itself contain peptides, development of competence was examined in the chemically
      defined medium (CDM) described by van de Rijn and Kessler (Infect. Immun. 27:444,
      1980). We confirmed a previous report that in this medium comS mutants of strain
      UA159 respond to a synthetic peptide comprising the seven C-terminal residues of
      ComS (ComS(11-17)) by increasing expression of the alternative sigma factor SigX,
      which in turn allows expression of competence effector genes. This response
      provided the basis for a bioassay for the ComS pheromone in the 100 to 1,000 nM
      range. It was further observed that comS(+) (but not comS mutant) cultures
      developed a high level of competence in the late log and transition phases of
      growth in this CDM without the introduction of any synthetic stimulatory peptide.
      This endogenous competence development was accompanied by extracellular release
      of one or more signals that complemented a comS mutation at levels equivalent to
      1 MUM synthetic ComS(11-17).

PMID- 22609912
TI  - Identification of Ata, a multifunctional trimeric autotransporter of
      Acinetobacter baumannii.
AB  - Acinetobacter baumannii has recently emerged as a highly troublesome nosocomial
      pathogen, especially in patients in intensive care units and in those undergoing
      mechanical ventilation. We have identified a surface protein adhesin of A.
      baumannii, designated the Acinetobacter trimeric autotransporter (Ata), that
      contains all of the typical features of trimeric autotransporters (TA), including
      a long signal peptide followed by an N-terminal, surface-exposed passenger domain
      and a C-terminal domain encoding 4 beta-strands. To demonstrate that Ata encoded
      a TA, we created a fusion protein in which we replaced the entire passenger
      domain of Ata with the epitope tag V5, which can be tracked with specific
      monoclonal antibodies, and demonstrated that the C-terminal 101 amino acids of
      Ata were capable of exporting the heterologous V5 tag to the surface of A.
      baumannii in a trimeric form. We found that Ata played a role in biofilm
      formation and bound to various extracellular matrix/basal membrane (ECM/BM)
      components, including collagen types I, III, IV, and V and laminin. Moreover, Ata
      mediated the adhesion of whole A. baumannii cells to immobilized collagen type IV
      and played a role in the survival of A. baumannii in a lethal model of systemic
      infection in immunocompetent mice. Taken together, these results reveal that Ata
      is a TA of A. baumannii involved in virulence, including biofilm formation,
      binding to ECM/BM proteins, mediating the adhesion of A. baumannii cells to
      collagen type IV, and contributing to the survival of A. baumannii in a mouse
      model of lethal infection.

PMID- 22609914
TI  - Extracellular identification of a processed type II ComR/ComS pheromone of
      Streptococcus mutans.
AB  - The competence-stimulating peptide (CSP) and the sigX-inducing peptide (XIP) are
      known to induce Streptococcus mutans competence for genetic transformation. For
      both pheromones, direct identification of the native peptides has not been
      accomplished. The fact that extracellular XIP activity was recently observed in a
      chemically defined medium devoid of peptides, as mentioned in an accompanying
      paper (K. Desai, L. Mashburn-Warren, M. J. Federle, and D. A. Morrison, J.
      Bacteriol. 194:3774-3780, 2012), provided ideal conditions for native XIP
      identification. To search for the XIP identity, culture supernatants were
      filtered to select for peptides of less than 3 kDa, followed by C(18) extraction.
      One peptide, not detected in the supernatant of a comS deletion mutant, was
      identified by tandem mass spectrometry (MS/MS) fragmentation as identical to the
      ComS C-terminal sequence GLDWWSL. ComS processing did not require Eep, a
      peptidase involved in processing or import of bacterial small hydrophobic
      peptides, since eep deletion had no inhibitory effect on XIP production or on
      synthetic XIP response. We investigated whether extracellular CSP was also
      produced. A reporter assay for CSP activity detection, as well as MS analysis of
      supernatants, revealed that CSP was not present at detectable levels. In
      addition, a mutant with deletion of the CSP-encoding gene comC produced
      endogenous XIP levels similar to those of a nondeletion mutant. The results
      indicate that XIP pheromone production is a natural phenomenon that may occur in
      the absence of natural CSP pheromone activity and that the heptapeptide GLDWWSL
      is an extracellular processed form of ComS, possibly the active XIP pheromone.
      This is the first report of direct identification of a ComR/ComS pheromone.

PMID- 22609915
TI  - Comparative genomic analyses of 17 clinical isolates of Gardnerella vaginalis
      provide evidence of multiple genetically isolated clades consistent with
      subspeciation into genovars.
AB  - Gardnerella vaginalis is associated with a spectrum of clinical conditions,
      suggesting high degrees of genetic heterogeneity among stains. Seventeen G.
      vaginalis isolates were subjected to a battery of comparative genomic analyses to
      determine their level of relatedness. For each measure, the degree of difference
      among the G. vaginalis strains was the highest observed among 23 pathogenic
      bacterial species for which at least eight genomes are available. Genome sizes
      ranged from 1.491 to 1.716 Mb; GC contents ranged from 41.18% to 43.40%; and the
      core genome, consisting of only 746 genes, makes up only 51.6% of each strain's
      genome on average and accounts for only 27% of the species supragenome. Neighbor
      grouping analyses, using both distributed gene possession data and core gene
      allelic data, each identified two major sets of strains, each of which is
      composed of two groups. Each of the four groups has its own characteristic genome
      size, GC ratio, and greatly expanded core gene content, making the genomic
      diversity of each group within the range for other bacterial species. To test
      whether these 4 groups corresponded to genetically isolated clades, we inferred
      the phylogeny of each distributed gene that was present in at least two strains
      and absent in at least two strains; this analysis identified frequent homologous
      recombination within groups but not between groups or sets. G. vaginalis appears
      to include four nonrecombining groups/clades of organisms with distinct gene
      pools and genomic properties, which may confer distinct ecological properties.
      Consequently, it may be appropriate to treat these four groups as separate
      species.

PMID- 22609916
TI  - Ligand-binding properties and conformational dynamics of autolysin repeat domains
      in staphylococcal cell wall recognition.
AB  - The bifunctional major autolysin Atl plays a key role in staphylococcal cell
      separation. Processing of Atl yields catalytically active amidase (AM) and
      glucosaminidase (GL) domains that are each fused to repeating units. The two
      repeats of AM (R1 and R2) target the enzyme to the septum, where it cleaves
      murein between dividing cells. We have determined the crystal structure of R2,
      which reveals that each repeat folds into two half-open beta-barrel subunits. We
      further demonstrate that lipoteichoic acid serves as a receptor for the repeats
      and that this interaction depends on conserved surfaces in each subunit. Small
      angle X-ray scattering of the mature amidase reveals the presence of flexible
      linkers separating the AM, R1, and R2 units. Different levels of flexibility for
      each linker provide mechanistic insights into the conformational dynamics of the
      full-length protein and the roles of its components in cell wall association and
      catalysis. Our analysis supports a model in which the repeats direct the
      catalytic AM domain to the septum, where it can optimally perform the final step
      of cell division.

PMID- 22609917
TI  - Selenium-dependent biogenesis of formate dehydrogenase in Campylobacter jejuni is
      controlled by the fdhTU accessory genes.
AB  - The food-borne bacterial pathogen Campylobacter jejuni efficiently utilizes
      organic acids such as lactate and formate for energy production. Formate is
      rapidly metabolized via the activity of the multisubunit formate dehydrogenase
      (FDH) enzyme, of which the FdhA subunit is predicted to contain a selenocysteine
      (SeC) amino acid. In this study we investigated the function of the cj1500 and
      cj1501 genes of C. jejuni, demonstrate that they are involved in selenium
      controlled production of FDH, and propose the names fdhT and fdhU, respectively.
      Insertional inactivation of fdhT or fdhU in C. jejuni resulted in the absence of
      FdhA and FdhB protein expression, reduced fdhABC RNA levels, the absence of FDH
      enzyme activity, and the lack of formate utilization, as assessed by (1)H nuclear
      magnetic resonance. The fdhABC genes are transcribed from a single promoter
      located two genes upstream of fdhA, and the decrease in fdhABC RNA levels in the
      fdhU mutant is mediated at the posttranscriptional level. FDH activity and the
      ability to utilize formate were restored by genetic complementation with fdhU and
      by supplementation of the growth media with selenium dioxide. Disruption of SeC
      synthesis by inactivation of the selA and selB genes also resulted in the absence
      of FDH activity, which could not be restored by selenium supplementation.
      Comparative genomic analysis suggests a link between the presence of selA and
      fdhTU orthologs and the predicted presence of SeC in FdhA. The fdhTU genes encode
      accessory proteins required for FDH expression and activity in C. jejuni,
      possibly by contributing to acquisition or utilization of selenium.

PMID- 22609918
TI  - Two surfaces of a conserved interdomain linker differentially affect output from
      the RST sensing module of the Bacillus subtilis stressosome.
AB  - The stressosome is a 1.8-MDa cytoplasmic complex that conveys environmental
      signals to the sigma(B) stress factor of Bacillus subtilis. A functionally
      irreducible complex contains multiple copies of three proteins: the RsbRA
      coantagonist, RsbS antagonist, and RsbT serine-threonine kinase. Homologues of
      these proteins are coencoded in different genome contexts in diverse bacteria,
      forming a versatile sensing and transmission module called RST after its common
      constituents. However, the signaling pathway within the stressosome itself is not
      well defined. The N-terminal, nonheme globin domains of RsbRA project from the
      stressosome and are presumed to channel sensory input to the C-terminal STAS
      domains that form the complex core. A conserved, 13-residue alpha-helical linker
      connects these domains. We probed the in vivo role of the linker using alanine
      scanning mutagenesis, assaying stressosome output in B. subtilis via a sigma(B)
      dependent reporter fusion. Substitutions at four conserved residues increased
      output 4- to 30-fold in unstressed cells, whereas substitutions at four
      nonconserved residues significantly decreased output. The periodicity of these
      effects supports a model in which RsbRA functions as a dimer in vivo, with the
      linkers forming parallel paired helices via a conserved interface. The
      periodicity further suggests that the opposite, nonconserved faces make
      additional contacts important for efficient stressosome operation. These results
      establish that the linker influences stressosome output under steady-state
      conditions. However, the stress response phenotypes of representative linker
      substitutions provide less support for the notion that the N-terminal globin
      domain senses acute environmental challenge and transmits this information via
      the linker helix.

PMID- 22609919
TI  - Degradation of 2,3-dihydroxybenzoate by a novel meta-cleavage pathway.
AB  - 2,3-Dihydroxybenzoate is the precursor in the biosynthesis of several
      siderophores and an important plant secondary metabolite that, in bacteria, can
      be degraded via meta-cleavage of the aromatic ring. The dhb cluster of
      Pseudomonas reinekei MT1 encodes a chimeric meta-cleavage pathway involved in the
      catabolism of 2,3-dihydroxybenzoate. While the first two enzymes, DhbA and DhbB,
      are phylogenetically related to those involved in 2,3-dihydroxy-p-cumate
      degradation, the subsequent steps are catalyzed by enzymes related to those
      involved in catechol degradation (DhbCDEFGH). Characterization of kinetic
      properties of DhbA extradiol dioxygenase identified 2,3-dihydroxybenzoate as the
      preferred substrate. Deletion of the encoding gene impedes growth of P. reinekei
      MT1 on 2,3-dihydroxybenzoate. DhbA catalyzes 3,4-dioxygenation with 2-hydroxy-3
      carboxymuconate as the product, which is then decarboxylated by DhbB to 2
      hydroxymuconic semialdehyde. This compound is then subject to dehydrogenation and
      further degraded to citrate cycle intermediates. Transcriptional analysis
      revealed genes of the dhB gene cluster to be highly expressed during growth with
      2,3-dihydroxybenzoate, whereas a downstream-localized gene encoding 2
      hydroxymuconic semialdehyde hydrolase, dispensable for 2,3-dihydroxybenzoate
      metabolism but crucial for 2,3-dihydroxy-p-cumate degradation, was only
      marginally expressed. This is the first report describing a gene cluster encoding
      enzymes for the degradation of 2,3-dihydroxybenzoate.

PMID- 22609920
TI  - Delineation of the caffeine C-8 oxidation pathway in Pseudomonas sp. strain CBB1
      via characterization of a new trimethyluric acid monooxygenase and genes involved
      in trimethyluric acid metabolism.
AB  - The molecular basis of the ability of bacteria to live on caffeine via the C-8
      oxidation pathway is unknown. The first step of this pathway, caffeine to
      trimethyluric acid (TMU), has been attributed to poorly characterized caffeine
      oxidases and a novel quinone-dependent caffeine dehydrogenase. Here, we report
      the detailed characterization of the second enzyme, a novel NADH-dependent
      trimethyluric acid monooxygenase (TmuM), a flavoprotein that catalyzes the
      conversion of TMU to 1,3,7-trimethyl-5-hydroxyisourate (TM-HIU). This product
      spontaneously decomposes to racemic 3,6,8-trimethylallantoin (TMA). TmuM prefers
      trimethyluric acids and, to a lesser extent, dimethyluric acids as substrates,
      but it exhibits no activity on uric acid. Homology models of TmuM against uric
      acid oxidase HpxO (which catalyzes uric acid to 5-hydroxyisourate) reveal a much
      bigger and hydrophobic cavity to accommodate the larger substrates. Genes
      involved in the caffeine C-8 oxidation pathway are located in a 25.2-kb genomic
      DNA fragment of CBB1, including cdhABC (coding for caffeine dehydrogenase) and
      tmuM (coding for TmuM). Comparison of this gene cluster to the uric acid
      metabolizing gene cluster and pathway of Klebsiella pneumoniae revealed two major
      open reading frames coding for the conversion of TM-HIU to S-(+)
      trimethylallantoin [S-(+)-TMA]. The first one, designated tmuH, codes for a
      putative TM-HIU hydrolase, which catalyzes the conversion of TM-HIU to 3,6,8
      trimethyl-2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (TM-OHCU). The second
      one, designated tmuD, codes for a putative TM-OHCU decarboxylase which catalyzes
      the conversion of TM-OHCU to S-(+)-TMA. Based on a combination of enzymology and
      gene-analysis, a new degradative pathway for caffeine has been proposed via TMU,
      TM-HIU, TM-OHCU to S-(+)-TMA.

PMID- 22609921
TI  - Novel role for RNase PH in the degradation of structured RNA.
AB  - Escherichia coli contains multiple 3' to 5' RNases, of which two, RNase PH and
      polynucleotide phosphorylase (PNPase), use inorganic phosphate as a nucleophile
      to catalyze RNA cleavage. It is known that an absence of these two enzymes causes
      growth defects, but the basis for these defects has remained undefined. To
      further an understanding of the function of these enzymes, the degradation
      pattern of different cellular RNAs was analyzed. It was observed that an absence
      of both enzymes results in the appearance of novel mRNA degradation fragments.
      Such fragments were also observed in strains containing mutations in RNase R and
      PNPase, enzymes whose collective absence is known to cause an accumulation of
      structured RNA fragments. Additional experiments indicated that the growth
      defects of strains containing RNase R and PNPase mutations were exacerbated upon
      RNase PH removal. Taken together, these observations suggested that RNase PH
      could play a role in structured RNA degradation. Biochemical experiments with
      RNase PH demonstrated that this enzyme digests through RNA duplexes of moderate
      stability. In addition, mapping and sequence analysis of an mRNA degradation
      fragment that accumulates in the absence of the phosphorolytic enzymes revealed
      the presence of an extended stem-loop motif at the 3' end. Overall, these results
      indicate that RNase PH plays a novel role in the degradation of structured RNAs
      and provides a potential explanation for the growth defects caused by an absence
      of the phosphorolytic RNases.

PMID- 22609922
TI  - Pseudomonas aeruginosa thiol peroxidase protects against hydrogen peroxide
      toxicity and displays atypical patterns of gene regulation.
AB  - The Pseudomonas aeruginosa PAO1 thiol peroxidase homolog (Tpx) belongs to a
      family of enzymes implicated in the removal of toxic peroxides. We have shown the
      expression of tpx to be highly inducible with redox cycling/superoxide generators
      and diamide and weakly inducible with organic hydroperoxides and hydrogen
      peroxide (H(2)O(2)). The PAO1 tpx pattern is unlike the patterns for other
      peroxide-scavenging genes in P. aeruginosa. Analysis of the tpx promoter reveals
      the presence of a putative IscR binding site located near the promoter. The tpx
      expression profiles in PAO1 and the iscR mutant, together with results from gel
      mobility shift assays showing that purified IscR specifically binds the tpx
      promoter, support the role of IscR as a transcriptional repressor of tpx that
      also regulates the oxidant-inducible expression of the gene. Recombinant Tpx has
      been purified and biochemically characterized. The enzyme catalyzes thioredoxin
      dependent peroxidation and can utilize organic hydroperoxides and H(2)O(2) as
      substrates. The Deltatpx mutant demonstrates differential sensitivity to H(2)O(2)
      only at moderate concentrations (0.5 mM) and not at high (20 mM) concentrations,
      suggesting a novel protective role of tpx against H(2)O(2) in P. aeruginosa.
      Altogether, P. aeruginosa tpx is a novel member of the IscR regulon and plays a
      primary role in protecting the bacteria from submillimolar concentrations of
      H(2)O(2).

PMID- 22609923
TI  - DprB facilitates inter- and intragenomic recombination in Helicobacter pylori.
AB  - For naturally competent microorganisms, such as Helicobacter pylori, the steps
      that permit recombination of exogenous DNA are not fully understood. Immediately
      downstream of an H. pylori gene (dprA) that facilitates high-frequency natural
      transformation is HP0334 (dprB), annotated to be a putative Holliday junction
      resolvase (HJR). We showed that the HP0334 (dprB) gene product facilitates high
      frequency natural transformation. We determined the physiologic roles of DprB by
      genetic analyses. DprB controls in vitro growth, survival after exposure to UV or
      fluoroquinolones, and intragenomic recombination. dprB ruvC double deletion
      dramatically decreases both homologous and homeologous transformation and
      survival after exposure to DNA-damaging agents. Moreover, the DprB protein binds
      to synthetic Holliday junction structures rather than double-stranded or single
      stranded DNA. These results demonstrate that the dprB product plays important
      roles affecting inter- and intragenomic recombination. We provide evidence that
      the two putative H. pylori HJRs (DprB and RuvC) have overlapping but distinct
      functions involving intergenomic (primarily DprB) and intragenomic (primarily
      RuvC) recombination.

PMID- 22609924
TI  - Identification of a third osmoprotectant transport system, the osmU system, in
      Salmonella enterica.
AB  - The growth of Salmonella enterica serovar Typhimurium mutants lacking the ProP
      and ProU osmoprotectant transport systems is stimulated by glycine betaine in
      high-osmolarity media, suggesting that this organism has an additional
      osmoprotectant transport system. Bioinformatic analysis revealed that the genome
      of this organism contains a hitherto-unidentified operon, designated osmU,
      consisting of four genes whose products show high similarity to ABC-type
      transport systems for osmoprotectants in other bacteria. The osmU operon was
      inactivated by a site-directed deletion, which abolished the ability of glycine
      betaine to alleviate the inhibitory effect of high osmolarity and eliminated the
      accumulation of [(14)C]glycine betaine and [(14)C]choline-O-sulfate in high
      osmolarity media in a strain lacking the ProP and ProU systems. Although the OsmU
      system can take up glycine betaine and choline-O-sulfate, these two
      osmoprotectants are recognized at low affinity by this transporter, suggesting
      that there might be more efficient substrates that are yet to be discovered. The
      transcription of osmU is induced 23-fold by osmotic stress (0.3 M NaCl). The osmU
      operon is present in the genomes of a number of Enterobacteriaceae, and orthologs
      of the OsmU system can be recognized in a wide variety of Bacteria and Archaea.
      The structure of the periplasmic binding protein component of this transporter,
      OsmX, was modeled on the crystallographic structure of the glycine betaine
      binding protein ProX of Archaeoglobus fulgidus; the resultant model indicated
      that the amino acids that constitute substrate-binding site, including an
      "aromatic cage" made up of four tyrosines, are conserved between these two
      proteins.

PMID- 22609925
TI  - CcpA-dependent carbohydrate catabolite repression regulates galactose metabolism
      in Streptococcus oligofermentans.
AB  - Streptococcus oligofermentans is an oral commensal that inhibits the growth of
      the caries pathogen Streptococcus mutans by producing copious amounts of H(2)O(2)
      and that grows faster than S. mutans on galactose. In this study, we identified a
      novel eight-gene galactose (gal) operon in S. oligofermentans that was comprised
      of lacABCD, lacX, and three genes encoding a galactose-specific transporter.
      Disruption of lacA caused more growth reduction on galactose than mutation of
      galK, a gene in the Leloir pathway, indicating that the principal role of this
      operon is in galactose metabolism. Diauxic growth was observed in cultures
      containing glucose and galactose, and a luciferase reporter fusion to the
      putative gal promoter demonstrated 12-fold repression of the operon expression by
      glucose but was induced by galactose, suggesting a carbon catabolite repression
      (CCR) control in galactose utilization. Interestingly, none of the single-gene
      mutations in the well-known CCR regulators ccpA and manL affected diauxic growth,
      although the operon expression was upregulated in these mutants in glucose. A
      double mutation of ccpA and manL eliminated glucose repression of galactose
      utilization, suggesting that these genes have parallel functions in regulating
      gal operon expression and mediating CCR. Electrophoretic mobility shift assays
      demonstrated binding of CcpA to the putative catabolite response element motif in
      the promoter regions of the gal operon and manL, suggesting that CcpA regulates
      CCR through direct regulation of the transcription of the gal operon and manL.
      This provides the first example of oral streptococci using two parallel CcpA
      dependent CCR pathways in controlling carbohydrate metabolism.

PMID- 22609926
TI  - Secretion genes as determinants of Bacillus anthracis chain length.
AB  - Bacillus anthracis grows in chains of rod-shaped cells, a trait that contributes
      to its escape from phagocytic clearance in host tissues. Using a genetic approach
      to search for determinants of B. anthracis chain length, we identified mutants
      with insertional lesions in secA2. All isolated secA2 mutants exhibited an
      exaggerated chain length, whereas the dimensions of individual cells were not
      changed. Complementation studies revealed that slaP (S-layer assembly protein), a
      gene immediately downstream of secA2 on the B. anthracis chromosome, is also a
      determinant of chain length. Both secA2 and slaP are required for the efficient
      secretion of Sap and EA1 (Eag), the two S-layer proteins of B. anthracis, but not
      for the secretion of S-layer-associated proteins or of other secreted products. S
      layer assembly via secA2 and slaP contributes to the proper positioning of BslO,
      the S-layer-associated protein, and murein hydrolase, which cleaves septal
      peptidoglycan to separate chains of bacilli. SlaP was found to be both soluble in
      the bacterial cytoplasm and associated with the membrane. The purification of
      soluble SlaP from B. anthracis-cleared lysates did not reveal a specific ligand,
      and the membrane association of SlaP was not dependent on SecA2, Sap, or EA1. We
      propose that SecA2 and SlaP promote the efficient secretion of S-layer proteins
      by modifying the general secretory pathway of B. anthracis to transport large
      amounts of Sap and EA1.

PMID- 22609927
TI  - Surface-layer (S-layer) proteins sap and EA1 govern the binding of the S-layer
      associated protein BslO at the cell septa of Bacillus anthracis.
AB  - The Gram-positive pathogen Bacillus anthracis contains 24 genes whose products
      harbor the structurally conserved surface-layer (S-layer) homology (SLH) domain.
      Proteins endowed with the SLH domain associate with the secondary cell wall
      polysaccharide (SCWP) following secretion. Two such proteins, Sap and EA1, have
      the unique ability to self-assemble into a paracrystalline layer on the surface
      of bacilli and form S layers. Other SLH domain proteins can also be found within
      the S layer and have been designated Bacillus S-layer-associated protein (BSLs).
      While both S-layer proteins and BSLs bind the same SCWP, their deposition on the
      cell surface is not random. For example, BslO is targeted to septal peptidoglycan
      zones, where it catalyzes the separation of daughter cells. Here we show that an
      insertional lesion in the sap structural gene results in elongated chains of
      bacilli, as observed with a bslO mutant. The chain length of the sap mutant can
      be reduced by the addition of purified BslO in the culture medium. This
      complementation in trans can be explained by an increased deposition of BslO onto
      the surface of sap mutant bacilli that extends beyond chain septa. Using
      fluorescence microscopy, we observed that the Sap S layer does not overlap the
      EA1 S layer and slowly yields to the EA1 S layer in a growth-phase-dependent
      manner. Although present all over bacilli, Sap S-layer patches are not observed
      at septa. Thus, we propose that the dynamic Sap/EA1 S-layer coverage of the
      envelope restricts the deposition of BslO to the SCWP at septal rings.

PMID- 22609928
TI  - cDNA cloning, characterization and expression of lipopolysaccharide and beta-1,3
      glucan binding protein (LGBP) gene from the Indian white shrimp Fenneropenaeus
      indicus.
AB  - A 1372bp full length cDNA of an LGBP gene was identified from the Indian white
      shrimp, Fenneropenaeus indicus. The open reading frame (ORF) of the F. indicus
      LGBP (Fein-LGBP) was 1164bp long, encoding a polypeptide of 388 amino acids. The
      Fein-LGBP deduced amino acid has conserved potential recognition motif for beta
      1, 3 linkages of polysaccharides and putative RGD (Arg-Gly-Asp) cell adhesion
      sites. Phylogenetic analysis revealed that the Fein-LGBP was grouped together
      with LGBPs of other crustaceans such as F. chinensis (91%, AAZ41363), Penaeus
      monodon (88%, AAM21213) and Litopenaeus vannamei (88%, ABU92557). Quantitative RT
      PCR results showed that Fein-LGBP gene expression was up-regulated in hemocytes
      following a 6h challenge in response to peptidoglycan (PG) and Vibrio
      parahaemolyticus. Messenger RNA transcripts of Fein-LGBP were measured in
      hemocytes of F. indicus from different molting stages. The highest Fein-LGBP mRNA
      expression was observed in pre-molting stages (D0/1) when compared to post-molt
      stages (A and B) and inter-molt stages (C). Fein-LGBP is involved in the
      regulation and activation of the prophenoloxidase cascade.

PMID- 22609929
TI  - Retention of solutes and different-sized particles in the digestive tract of the
      ostrich (Struthio camelus massaicus), and a comparison with mammals and reptiles.
AB  - Ostriches (Struthio camelus) achieve digesta retention times, digesta particle
      size reduction and digestibilities equal to similar-sized herbivorous mammals, in
      contrast to some other avian herbivores. The sequence of digestive processes in
      their gastrointestinal tract, however, is still unexplored. Using two groups of
      four ostriches (mean body mass 75.1 +/- 17.3 kg) kept on fresh alfalfa, we tested
      the effect of two intake levels (17 and 42 g dry matter kg(-0.75)d(-1)) on the
      mean retention time (MRT) of a solute and three different-sized (2, 10, 20 mm)
      particle markers, mean faecal particle size (MPS), and digestibility. Intake
      level did not affect MRT, but MPS (0.74 vs. 1.52 mm) and dry matter digestibility
      (81 vs. 78%). The solute marker (MRT 22-26 h) was excreted faster than the
      particle markers; there was no difference in the MRT of 10 and 20 mm particles
      (MRT 28-32 h), but 2mm particles were retained longer (MRT 39-40 h). Because the
      solute marker was not selectively retained, and wet-sieving of gut contents of
      slaughtered animals did not indicate smaller particles in the caeca, the long MRT
      of small particles is interpreted as intermittent excretion from the gizzard,
      potentially due to entrapment in small grit. The marker excretion pattern also
      showed intermittent peaks for all markers in five of the animals, which indicates
      non-continuous outflow from the gizzard. When adding our data to literature data
      on avian herbivores, a dichotomy is evident, with ostrich and hoatzin
      (Opisthocomus hoazin) displaying long MRTs, high digestibilities, and gut
      capacities similar to mammalian herbivores, and other avian herbivores such as
      grouse, geese or emus with shorter MRTs, lower fibre digestibilities and lower
      gut capacities. In the available data for all avian herbivores where food intake
      and MRTs were measured, this dichotomy and food intake level, but not body mass,
      was related to MRT, adding to the evidence that body mass itself may not be sole
      major determinant of digestive physiology. The most striking difference between
      mammalian and avian herbivores from the literature is the fundamentally lower
      methane production measured in the very few studies in birds including ostriches,
      which appears to be at the level of reptiles, in spite of general food intake
      levels of a magnitude as in mammals. Further studies in ostriches and other avian
      herbivores are required to understand the differences in digestive mechanisms
      between avian and mammalian herbivores.

PMID- 22609930
TI  - Titration of synaptotagmin I expression differentially regulates release of
      norepinephrine and neuropeptide Y.
AB  - Synaptotagmin (syt) I is a Ca(2+) sensor that has been thought to trigger all
      vesicle secretion with similar mechanisms. However, given the calcium and
      stimulation requirements of small clear, and large dense core vesicles, we
      hypothesized that syt I expression differentially regulates vesicle release.
      Therefore, in this study, we generated multiple stable cell lines of PC12 cells
      that each had a different and stable level of syt I expression. We determined the
      functional effects of titrated syt I expression on transmitter release from the
      two vesicle types, and showed that the transmitters, norepinephrine (NE) and
      neuropeptide Y (NPY), each have a threshold level of syt I expression required
      for their release that is different for the two transmitter types. We used carbon
      fiber amperometry to measure release of NE from single vesicles, and found that
      release ranged from 50% to 100% in the syt I-targeted cells compared to release
      from control cells. We used an immunoassay to measure NPY release and found that
      NPY release was abolished in cells that had abolished syt I expression, but cell
      lines that expressed 50-60% of control levels of syt I exhibited NPY release
      levels comparable to release of NPY from control cells. Furthermore, the vesicle
      fusion pore exhibited a reduced open duration when syt I was abolished, but a
      longer open duration time for 50% syt I expression than control cells. Therefore,
      vesicles have a threshold for syt I that is required to control opening of the
      fusion pore, expansion, and full fusion to release large dense core proteins, but
      not for full fusion of the small molecules like NE.

PMID- 22609931
TI  - Individual differences in trait anxiety are associated with white matter tract
      integrity in the left temporal lobe in healthy males but not females.
AB  - The temporal lobe plays a major role in anxiety and depression disorders and is
      also of importance for trait anxiety in the non-pathological range. The present
      study investigates self-report data of personality dimensions linked to trait
      anxiety in the context of white matter tract integrity in the temporal lobes of
      the human brain in a large sample of N=110 healthy participants. The results show
      that especially in men values for fractional anisotropy of several white matter
      tracts in the temporal lobe of the left hemisphere correlate substantially with
      individual differences in trait anxiety (depending on the tract investigated
      between .40 and .49). The present study shows that not only data from functional
      magnetic resonance imaging (fMRI), but also from structural diffusion tensor
      imaging (DTI) provide interesting insights into the biological foundation of
      human personality traits.

PMID- 22609933
TI  - 1H NMR-based metabonomics in brain nucleus accumbens and striatum following
      repeated cocaine treatment in rats.
AB  - Studies have shown a few cerebral metabolites modified by cocaine in brain
      regions; however, endogenous metabolic profiling has been lacking. Ex vivo (1)H
      NMR (hydrogen-1 nuclear magnetic resonance) spectroscopy-based metabonomic
      approach coupled with partial least squares was applied to investigate the
      changes of cerebral metabolites in nucleus accumbens (NAc) and striatum of rats
      subjected to cocaine treatment. Our results showed that both single and repeated
      cocaine treatment can induce significant changes in a couple of cerebral
      metabolites. The increase of neurotransmitters glutamate and gamma-amino butyric
      acid (GABA) were observed in NAc and striatum from the rats repeatedly treated
      with cocaine. Creatine and taurine increased in NAc whereas taurine increased and
      creatine decreased in striatum after repeated cocaine treatment. Elevation of N
      acetylaspartate in NAc and striatum and decrease of lactate in striatum were
      observed, which may reflect the mitochondria dysregulation caused by cocaine;
      moreover, alterations of choline, phosphocholine and glycerol in NAc and striatum
      could be related to membrane disruption. Moreover, groups of rats with and
      without conditioned place preference (CPP) apparatus are presenting difference in
      metabolites. Collectively, our results provide the first evidence of metabonomic
      profiling of NAc and striatum in response to cocaine, exhibiting a regionally
      specific alteration patterns. We find that repeated cocaine administration leads
      to significant metabolite alterations, which are involved in neurotransmitter
      disturbance, oxidative stress, mitochondria dysregulation and membrane disruption
      in brain.

PMID- 22609932
TI  - Role of cerebral endothelial cells in the astrocyte swelling and brain edema
      associated with acute hepatic encephalopathy.
AB  - Brain edema is an important complication of acute hepatic encephalopathy (AHE),
      and astrocyte swelling is largely responsible for its development. Elevated blood
      and brain ammonia levels have been considered as major etiological factors in
      this edema. In addition to ammonia, recent studies have suggested that systemic
      infection, inflammation (and associated cytokines (CKs)), as well as endotoxin
      (lipopolysaccharide (LPS)) are also involved in AHE-associated brain edema. As
      endothelial cells (ECs) are the first resident brain cells exposed to blood-borne
      "noxious agents" (i.e., ammonia, CKs, LPS) that are present in AHE, these cells
      may be in a critical position to react to these agents and trigger a process
      resulting in astrocyte swelling/brain edema. We therefore examined the effect of
      conditioned media (CM) from ammonia, LPS and cytokine-treated cultured brain ECs
      on cell swelling in cultured astrocytes. CM from ammonia-treated ECs when added
      to astrocytes caused significant cell swelling, and such swelling was potentiated
      when astrocytes were exposed to CM from ECs treated with a combination of
      ammonia, LPS and CKs. We also found an additive effect when astrocytes were
      exposed to ammonia along with CM from ammonia-treated ECs. Additionally, ECs
      treated with ammonia showed a significant increase in the production of oxy
      radicals, nitric oxide (NO), as well as evidence of oxidative/nitrative stress
      and activation of the transcription factor nuclear factor kappa B (NF-kappaB). CM
      derived from ECs treated with ammonia, along with antioxidants (AOs) or the NF
      kappaB inhibitor BAY 11-7082, when added to astrocytes resulted in a significant
      reduction in cell swelling, as compared to the effect of CM from ECs-treated only
      with ammonia. We also identified increased nuclear NF-kappaB expression in rat
      brain cortical ECs in the thioacetamide (TAA) model of AHE. These studies suggest
      that ECs significantly contribute to the astrocyte swelling/brain edema in AHE,
      likely as a consequence of oxidative/nitrative stress and activation of NF
      kappaB.

PMID- 22609934
TI  - Sex differences in the expression of vasotocin/isotocin, gonadotropin-releasing
      hormone, and tyrosine and tryptophan hydroxylase family genes in the medaka
      brain.
AB  - In teleost fish, sex differences in several behavioral and physiological traits
      have been assumed to reflect underlying sex differences in the central expression
      of neurotransmitter/neuromodulator-related molecules, including vasotocin
      (VT)/isotocin (IT), gonadotropin-releasing hormone (GnRH), and tyrosine and
      tryptophan hydroxylases (TH and TPH). However, the sex-dependent expression
      patterns of these molecules have not been fully characterized in the teleost
      brain. In the present study, we therefore systematically evaluated sex
      differences in their expression in the medaka (Oryzias latipes) brain. The most
      prominent sex difference was observed in vt expression in the nucleus posterior
      tuberis (NPT) and the posterior part of the nucleus ventral tuberis (NVT) in the
      hypothalamus, where the expression was completely male-specific. Male-biased
      expression of gnrh1, tph1, and tph2 was also evident in the supracommissural and
      posterior nuclei of the ventral telencephalic area (Vs/Vp), medial nucleus of the
      dorsal telencephalic area (Dm), and thalamic dorsal posterior nucleus (DP),
      respectively. In contrast, the overall expression levels of it and gnrh3 were
      higher in the female brain than in the male brain. Equally importantly, no
      conspicuous sex differences were observed in the expression of gnrh2, th1, and
      th2, despite several previous reports of their sex-biased expression in the
      brains of other teleost species. Taken together, these data have uncovered
      previously unidentified sex differences in the expression of VT/IT, GnRH, and TPH
      in the teleost brain, which may possibly be relevant to sexual dimorphism in some
      behavioral and/or physiological traits, and have simultaneously highlighted
      potential species differences in the roles of these molecules.

PMID- 22609936
TI  - Increased perivascular laminin predicts damage to astrocytes in CA3 and piriform
      cortex following chemoconvulsive treatments.
AB  - Status epilepticus (SE) induced by pilocarpine or kainate is associated with yet
      not systemically investigated astrocytic and vascular injuries. To investigate
      their possible association with neuronal damage, the changes in glial fibrillary
      acidic protein (GFAP), laminin and neuron-specific nuclear protein (NeuN)
      immunoreactivities were analyzed in rats treated with pilocarpine (380 mg/kg) or
      kainate (15 mg/kg), and receiving diazepam (20mg/kg) after 10 min of SE. A
      different group of rats was injected with endothelin-1 (ET-1) in the caudate
      putamen to reproduce the changes in GFAP and laminin immunoreactivities
      associated with ischemia. Focal loss of GFAP immunostaining was accompanied by
      increased laminin immunoreactivity in blood vessels, in all the examined groups.
      Regression analysis revealed a significant (P<0.01) relationship between
      astrocytic lesion and increased laminin immunoreactivity in the piriform cortex
      (Pir) of both pilocarpine (R(2)=0.88) and kainate (R(2)=0.94) groups of
      treatment. A significant relationship (P<0.01; R(2)=0.81) was also present in the
      cornu Ammonis 3 (CA3) hippocampal region of pilocarpine-treated rats. At
      variance, neuronal and glial lesions were significantly related (P<0.05,
      R(2)=0.74) only in the substantia nigra of pilocarpine-treated rats. The ratio
      between areas of GFAP and laminin changes of immunoreactivity in the ET-1 group
      was similar to those found in pilocarpine- and kainate-treated rats in specific
      brain regions, such as the hippocampal CA3 subfield, Pir and the anterior
      olfactory nucleus. The amygdala and submedius thalamic nucleus in the pilocarpine
      group, and the perirhinal and entorhinal cortices in the kainate group, also
      presented ischemic-like changes. These results indicate that laminin
      immunoreactivity is upregulated in the basal lamina of blood vessels after SE
      induced by pilocarpine or kainate. This phenomenon is significantly associated
      with lesions involving more glial than neuronal cells, in specific cerebral
      regions.

PMID- 22609935
TI  - Group III metabotropic glutamate receptors and transient receptor potential
      vanilloid 1 co-localize and interact on nociceptors.
AB  - Several lines of evidence indicate group III metabotropic glutamate receptors
      (mGluRs) have systemic anti-hyperalgesic effects. We hypothesized this could
      occur through modulation of transient receptor potential vanilloid 1 (TRPV1)
      receptors on nociceptors. To address this question we performed anatomical
      studies to determine if group III mGluRs were expressed on cutaneous axons and if
      they co-localized with TRPV1. Immunostaining at the electron microscopic level
      demonstrated that 22% of unmyelinated axons labeled for mGluR8. Immunostaining at
      the light microscopic level in lumbar dorsal root ganglia (DRG) demonstrated that
      80% and 28% of neurons labeled for mGluR8 or TRPV1, respectively. Of those
      neurons labeled for mGluR8, 25% labeled for TRPV1; of those labeled for TRPV1,
      71% labeled for mGluR8. In behavior studies intraplantar injection of the group
      III mGluR agonist, L-(+)-2-amino-4-phosphonobutyric acid (L-AP-4: 0.1, 1.0, and
      10.0 MUM) had no effect on paw withdrawal latency (PWL) to heat in naive rats but
      administration of 10 MUM L-AP-4 prior to 0.05% capsaicin (CAP), significantly
      attenuated CAP-induced lifting/licking and reduced flinching behavior. The L-AP-4
      effect was specific since administration of a group III antagonist alpha-methyl-3
      methyl-4-phosphonophenylglycine (UBP1112) (100MUM) blocked the L-AP-4 effect on
      CAP, resulting in behaviors similar to CAP alone. Intraplantar injection of
      UBP1112 alone did not result in nociceptive behaviors, indicating group III
      mGluRs are not tonically active. Finally, the anti-hyperalgesic effect of group
      III in this paradigm was local and not systemic since intraplantar administration
      of L-AP-4 in one hind paw did not attenuate nociceptive behaviors following CAP
      injection in the contralateral hind paw. Adenyl cyclase/cyclic AMP/PKA may be the
      second messenger pathway linking these two receptor families because intraplantar
      injection of forskolin (FSK, 10 MUM) reduced PWL to heat and L-AP-4 reversed this
      FSK effect. Taken together, these results suggest group III mGluRs can negatively
      modulate TRPV1 through inhibition of adenyl cyclase and downstream intracellular
      activity, blocking TRPV1-induced activation of nociceptors.

PMID- 22609937
TI  - Immunohistochemical demonstration of increased prostaglandin F2alpha levels in
      the rat hippocampus following kainic acid-induced seizures.
AB  - Prostaglandin (PG) F(2alpha) is one of the major prostanoids biosynthesized by
      cyclooxygenases (COXs) from arachidonic acid. Although it has been reported that
      there is a selective surge in PGF(2alpha) production in the hippocampus during
      kainic acid (KA)-induced seizure activity, the precise intra-hippocampal
      distribution of PGF(2alpha) has not been elucidated due to the paucity of
      effective histological techniques for detecting PGs in tissues. We investigated
      the tissue distribution of PGF(2alpha) in the rat hippocampus 30 min after KA
      injection by developing fixation and immunohistological-staining methods. To
      detect PGF(2alpha) directly on histological sections, we used systemic perfusion
      fixation with water-soluble carbodiimide fixative, followed by immersion of the
      brains in Zamboni's fixative. We then performed immunofluorescence staining with
      anti-PGF(2alpha) antibody, with negative control experiments used to confirm the
      staining specificity. Definitive immunolabeling for PGF(2alpha) was evident most
      markedly in pyramidal cells of the hippocampal cornu Ammonis (CA) 3 sector and
      neurons of the hilus in KA-treated rats. Immunolabeling for PGF(2alpha) was also
      evident in granule cells of the dentate gyrus. Double immunfluorescence staining
      revealed that PGF(2alpha)-immunopositive neurons expressed cytosolic
      phospholipases A(2), COX-2, and FP receptor. These results suggest that the major
      source of PGF(2alpha) production immediately after KA injection was neurons of
      the hippocampal CA3 sector, hilus and dentate gyrus. These neurons exert
      PGF(2alpha)-mediated functions via FP receptors in an autocrine/paracrine manner
      and may play pathophysiological roles in the acute phase (30 min) of
      excitotoxicity.

PMID- 22609938
TI  - Identification of mRNA for endocannabinoid biosynthetic enzymes within
      hippocampal pyramidal cells and CA1 stratum radiatum interneuron subtypes using
      quantitative real-time polymerase chain reaction.
AB  - The hippocampus is required for short-term memory and contains both excitatory
      pyramidal cells and inhibitory interneurons. These cells exhibit various forms of
      synaptic plasticity, the mechanism underlying learning and memory. More recently,
      endocannabinoids were identified to be involved in synaptic plasticity. Our goal
      was to describe the distribution of endocannabinoid biosynthetic enzymes within
      CA1 stratum radiatum interneurons and CA3/CA1 pyramidal cells. We extracted mRNA
      from single interneurons and pyramidal cells and used real-time quantitative
      polymerase chain reaction (RT-PCR) to detect the presence of 12-lipoxygenase, N
      acyl-phosphatidylethanolamine-specific phospholipase D, diacylglycerol lipase
      alpha, and type I metabotropic glutamate receptors, all known to be involved in
      endocannabinoid production and plasticity. We observed that the expression of
      endocannabinoid biosynthetic enzyme mRNA does occur within interneurons and that
      it is coexpressed with type I metabotropic glutamate receptors, suggesting
      interneurons have the potential to produce endocannabinoids. We also identified
      that CA3 and CA1 pyramidal cells express endocannabinoid biosynthetic enzyme
      mRNA. Our data provide the first molecular biological evidence for putative
      endocannabinoid production in interneurons, suggesting their potential ability to
      regulate endocannabinoid-mediated processes, such as synaptic plasticity.

PMID- 22609939
TI  - Systemic pregabalin attenuates sensorimotor responses and medullary glutamate
      release in inflammatory tooth pain model.
AB  - Our previous studies have demonstrated that application of inflammatory irritant
      mustard oil (MO) to the tooth pulp induces medullary glutamate release and
      central sensitization in the rat medullary dorsal horn (MDH), as well as
      nociceptive sensorimotor responses in craniofacial muscles in rats. There is
      recent evidence that anticonvulsant drugs such as pregabalin that influence
      glutamatergic neurotransmission are effective in several pain states. The aim of
      this study was to examine whether systemic administration of pregabalin
      attenuated glutamate release in the medulla as well as these nociceptive effects
      reflected in increased electromyographic (EMG) activity induced by MO application
      to the tooth pulp. Male adult rats were anesthetized with isofluorane (1.0-1.2%),
      and jaw and tongue muscle EMG activities were recorded by needle electrodes
      inserted bilaterally into masseter and anterior digastric muscles and into the
      genioglossus muscle, and also the medullary release of glutamate was assessed by
      in vivo microdialysis. Pregabalin or vehicle control (isotonic saline) was
      administered 30 min before the pulpal application of MO or vehicle control
      (mineral oil). Application of mineral oil to the maxillary first molar tooth pulp
      produced no change in baseline EMG activity and glutamate release. However,
      application of MO to the pulp significantly increased both the medullary release
      of glutamate and EMG activity in the jaw and tongue muscles for several minutes.
      In contrast, pre-medication with pregabalin, but not vehicle control,
      significantly and dose-dependently attenuated the medullary glutamate release and
      EMG activity in these muscles after MO application to the tooth pulp (analysis of
      variance (ANOVA), p<0.05). These results suggest that pregabalin may attenuate
      the medullary release of glutamate and associated nociceptive sensorimotor
      responses in this acute inflammatory pulpal pain model, and that it may prove
      useful for the treatment of orofacial inflammatory pain states.

PMID- 22609940
TI  - Agmatine selectively improves behavioural function in aged male Sprague-Dawley
      rats.
AB  - L-arginine, a semi-essential amino acid, can be metabolized to form a number of
      bioactive molecules. Nitric oxide (NO), generated by NO synthase (NOS) from L
      arginine, has been strongly implicated in the aging process. Agmatine,
      decarboxylated arginine, regulates the production of NO and other metabolites of
      L-arginine, modulates behavioural function, and has anti-inflammatory and
      neuroprotective effects. The present study investigated whether agmatine
      supplementation could improve behavioural function in aged male Sprague-Dawley
      rats, and could attenuate age-related changes in NOS activity and protein
      expression in memory-related structures. Aged rats treated with saline displayed
      significantly reduced exploratory activity and impaired spatial reference and
      working memory and object recognition memory. Agmatine (40 mg/kg) administered
      intraperitoneally significantly improved spatial working memory and object
      recognition memory in aged rats, suppressed age-related elevation in total NOS
      activity, and restored endothelial NOS protein to the normal level. However,
      agmatine supplementation was unable to improve exploratory activity and spatial
      reference learning and memory in aged rats. These findings suggest that exogenous
      agmatine selectively improves behavioural function in aged rats under the present
      experimental condition, and merit future investigation of its therapeutic
      potential in cognitive decline during aging.

PMID- 22609941
TI  - Selective loss of AMPA receptors at corticothalamic synapses in the epileptic
      stargazer mouse.
AB  - Absence seizures are common in the stargazer mutant mouse. The mutation
      underlying the epileptic phenotype in stargazers is a defect in the gene encoding
      the normal expression of the protein stargazin. Stargazin is involved in the
      membrane trafficking and synaptic targeting of alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid receptors (AMPARs) at excitatory glutamatergic synapses.
      Thus, the genetic defect in the stargazer results in a loss of AMPARs and
      consequently, excitation at glutamatergic synapses. Absence seizures are known to
      arise in thalamocortical networks. In the present study we show for the first
      time, using Western blot analysis and quantitative immunogold cytochemistry, that
      in the epileptic stargazer mouse, there is a global loss of AMPAR protein in
      nucleus reticularis (RTN) and a selective loss of AMPARs at corticothalamic
      synapses in inhibitory neurons of the RTN thalamus. In contrast, there is no
      significant loss of AMPARs at corticothalamic synapses in excitatory relay
      neurons in the thalamic ventral posterior (VP) region. The findings of this study
      thus provide cellular and molecular evidence for a selective regional loss of
      synaptic AMPAR within the RTN that could account for the loss of function at
      these inhibitory neuron synapses, which has previously been reported from
      electrophysiological studies. The specific loss of AMPARs at RTN but not relay
      synapses in the thalamus of the stargazer, could contribute to the absence
      epilepsy phenotype by altering thalamocortical network oscillations. This is
      supported by recent evidence that loss of glutamate receptor subunit 4 (GluA4)
      (the predominant AMPAR-subtype in the thalamus), also leads to a specific
      reduction in strength in the cortico-RTN pathway and enhanced thalamocortical
      oscillations, in the Gria4(-/-) model of absence epilepsy. Thus further study of
      thalamic changes in these models could be important for future development of
      drugs targeted to absence epilepsy.

PMID- 22609942
TI  - Suppression of endothelial cell adhesion by XJP-1, a new phenolic compound
      derived from banana peel.
AB  - The adhesion of monocytes to activated vascular endothelial cells is a critical
      event in the initiation of atherosclerosis. Adhesion is mediated by oxidized low
      density lipoprotein (ox-LDL) which up-regulates inflammatory markers on
      endothelial cells. Here we report that (+/-) 7, 8-dihydroxy-3-methyl
      isochromanone-4 (XJP-1), an inhibitor of ox-LDL-induced adhesion of monocytes to
      endothelial cells blocks cellular functions which are associated with adhesion.
      We show that XJP-1 down-regulates ox-LDL-induced over-expression of adhesion
      molecules (ICAM-1 and VCAM-1) in a dose-dependent manner in human umbilical vein
      endothelial cells (HUVECs), attenuates ox-LDL-induced up-regulation of low
      density lipoprotein receptor (LOX)-1, decreases generation of reactive oxygen
      species (ROS), blocks translocation of nuclear factor-kappa B (NF-kappaB)
      activity, and prevents activation of c-Jun N-terminal kinase (JNK)/p38 pathways
      in endothelial cells. These findings suggest that XJP-1 may attenuate ox-LDL
      induced endothelial adhesion of monocytes by blocking expression of adhesion
      molecules through suppressing ROS/NF-kappaB, JNK and p38 pathways.

PMID- 22609943
TI  - Role of Mos/MEK/ERK cascade and Cdk1 in Ca2+ oscillations in fertilized ascidian
      eggs.
AB  - Intracellular calcium ion concentration ([Ca(2+)](i)) transients are observed in
      the fertilized eggs of all species investigated so far, and are critical for
      initiating several events related to egg activation and cell cycle control. Here,
      we investigated the role of the Mos/MEK/ERK cascade and Cdk1 on Ca(2+)
      oscillations in fertilized ascidian eggs. The egg of the ascidian Phallusia nigra
      shows [Ca(2+)](i) oscillations after fertilization: Ca(2+) waves immediately
      following fertilization (phase I), and [Ca(2+)](i) oscillations between the first
      and second polar body extrusions (phase II). Our results show that in P. nigra
      eggs, ERK activity peaked just before the extrusion of the first polar body, and
      decreased gradually, eventually disappearing at the extrusion of the second polar
      body. Cyclin-dependent protein kinase 1(Cdk1) activity decreased to undetectable
      levels immediately after fertilization, and then periodically increased according
      to the meiotic and mitotic cell cycle. When the unfertilized eggs were incubated
      with U0126, an inhibitor of MEK, before insemination, ERK was immediately
      inactivated, and the phase II [Ca(2+)](i) oscillations disappeared.
      Alternatively, when the constitutively active Mos protein (GST-Mos) was injected
      into the unfertilized eggs, ERK activity was preserved for at least 120 min after
      fertilization, and the phase II [Ca(2+)](i) oscillations lasted for more than 120
      min after the second polar body extrusion. These results suggest that ERK
      activity is necessary for maintaining [Ca(2+)](i) oscillations. GST-DeltaN85
      cyclin, which maintains Cdk1 activity, caused ERK activity in the eggs to persist
      for over 120 min after fertilization, and prolonged [Ca(2+)](i) oscillations.
      Moreover, the effects of GST-DeltaN85-cyclin on the egg were abrogated by the
      application of U0126. Thus, Cdk1-mediated [Ca(2+)](i) oscillations seem to
      require ERK activity. However, GST-Mos triggered [Ca(2+)](i) oscillations after
      the second polar body extrusion, whereas GST-DeltaN85-cyclin did not, although it
      prolongs the duration of [Ca(2+)](i) oscillations. Interestingly, GST-DeltaN85
      cyclin increased the frequency of [Ca(2+)](i) transients in the Mos-induced
      [Ca(2+)](i) oscillations after the extrusion of the second polar body. Thus, Cdk1
      could maintain, but not activate, ERK and [Ca(2+)](i) oscillations. ERK activity
      and [Ca(2+)](i) oscillations seem to form a negative feedback loop which may be
      responsible for maintaining the meiotic period.

PMID- 22609945
TI  - Conformational dynamics of human IAPP monomers.
AB  - We study the conformational dynamics of the human Islet Amyloid Polypeptide
      (hIAPP) molecule - a 37 residue-long peptide associated to type 2 diabetes -
      using molecular dynamics (MD) simulations. We identify partially structured
      conformational states of the hIAPP monomer, categorized by both end-to-end
      distance and secondary structure, as suggested by previous experimental and
      computational studies. The MD trajectories of hIAPP are analyzed using data
      driven methods, in particular principal component analysis, in order to identify
      preferred conformational states of the amylin monomer and to discuss their
      relative stability as compared to corresponding states in the amylin dimer. These
      potential hIAPP conformational states could be further tested and described
      experimentally, or in conjunction with modern computational analysis tools such
      as Markov state-based methods for extracting kinetics and thermodynamics from
      atomistic MD trajectories.

PMID- 22609944
TI  - The FGF8-related signals Pyramus and Thisbe promote pathfinding, substrate
      adhesion, and survival of migrating longitudinal gut muscle founder cells.
AB  - Fibroblast growth factors (FGFs) frequently fulfill prominent roles in the
      regulation of cell migration in various contexts. In Drosophila, the FGF8-like
      ligands Pyramus (Pyr) and Thisbe (Ths), which signal through their receptor
      Heartless (Htl), are known to regulate early mesodermal cell migration after
      gastrulation as well as glial cell migration during eye development. Herein, we
      show that Pyr and Ths also exert key roles during the long-distance migration of
      a specific sub-population of mesodermal cells that migrate from the caudal
      visceral mesoderm within stereotypic bilateral paths along the trunk visceral
      mesoderm toward the anterior. These cells constitute the founder myoblasts of the
      longitudinal midgut muscles. In a forward genetic screen for regulators of this
      morphogenetic process we identified loss of function alleles for pyr. We show
      that pyr and ths are expressed along the paths of migration in the trunk visceral
      mesoderm and endoderm and act largely redundantly to help guide the founder
      myoblasts reliably onto and along their substrate of migration. Ectopically
      provided Pyr and Ths signals can efficiently re-rout the migrating cells, both in
      the presence and absence of endogenous signals. Our data indicate that the
      guidance functions of these FGFs must act in concert with other important
      attractive or adhesive activities of the trunk visceral mesoderm. Apart from
      their guidance functions, the Pyr and Ths signals play an obligatory role for the
      survival of the migrating cells. Without these signals, essentially all of these
      cells enter cell death and detach from the migration substrate during early
      migration. We present experiments that allowed us to dissect the roles of these
      FGFs as guidance cues versus trophic activities during the migration of the
      longitudinal visceral muscle founders.

PMID- 22609946
TI  - Obesity is mediated by differential aryl hydrocarbon receptor signaling in mice
      fed a Western diet.
AB  - BACKGROUND: Obesity is a growing worldwide problem with genetic and environmental
      causes, and it is an underlying basis for many diseases. Studies have shown that
      the toxicant-activated aryl hydrocarbon receptor (AHR) may disrupt fat metabolism
      and contribute to obesity. The AHR is a nuclear receptor/transcription factor
      that is best known for responding to environmental toxicant exposures to induce a
      battery of xenobiotic-metabolizing genes. OBJECTIVES: The intent of the work
      reported here was to test more directly the role of the AHR in obesity and fat
      metabolism in lieu of exogenous toxicants. METHODS: We used two congenic mouse
      models that differ at the Ahr gene and encode AHRs with a 10-fold difference in
      signaling activity. The two mouse strains were fed either a low-fat (regular)
      diet or a high-fat (Western) diet. RESULTS: The Western diet differentially
      affected body size, body fat:body mass ratios, liver size and liver metabolism,
      and liver mRNA and miRNA profiles. The regular diet had no significant
      differential effects. CONCLUSIONS: The results suggest that the AHR plays a large
      and broad role in obesity and associated complications, and importantly, may
      provide a simple and effective therapeutic strategy to combat obesity, heart
      disease, and other obesity-associated illnesses.

PMID- 22609947
TI  - Hierarchical self-assembly of hexagonal single-crystal nanosheets into 3D layered
      superlattices with high conductivity.
AB  - While the number of man-made nano superstructures realized by self-assembly is
      growing in recent years, assemblies of conductive polymer nanocrystals,
      especially for superlattices, are still a significant challenge, not only because
      of the simplicity of the shape of the nanocrystal building blocks and their
      interactions, but also because of the poor control over these parameters in the
      fabrication of more elaborate nanocrystals. Here, we firstly report a facile and
      general route to a new generation of 3D layered superlattices of polyaniline
      doped with CSA (PANI-CSA) and show how PANI crystallize and self-assemble, in a
      suitable single solution environment. In cyclohexane, 1D amorphous nanofibers
      transformed to 1D nanorods as building blocks, and then to 2D single-crystal
      nanosheets with a hexagonal phase, and lastly to 3D ordered layered superlattices
      with the narrowest polydispersity value (M(w)/M(n) = 1.47). Remarkably, all the
      instructions for the hierarchical self-assembly are encoded in the layered shape
      in other non-polar solvents (hexane, octane) and their conductivity in the pi-pi
      stacking direction is improved to about 50 S cm(-1), which is even higher than
      that of the highest previously reported value (16 S cm(-1)). The method used in
      this study is greatly expected to be readily scalable to produce superlattices of
      conductive polymers with high quality and low cost.

PMID- 22609949
TI  - Antimicrobial agent, tetracycline, enhanced upper alimentary tract Candida
      albicans infection and its related mucosal proliferation in alloxan-induced
      diabetic rats.
AB  - Alloxan-induced diabetic rats showed proliferative changes in the forestomach,
      accompanied by chronic inflammation, and one lesion progress to squamous cell
      carcinoma (SCC) without distant metastasis. The authors demonstrated that these
      lesions might be caused by Candida albicans infection. Antimicrobial therapy,
      particularly tetracycline treatment, has been blamed for a reduction in the
      number of competing bacterial organisms, which is frequently mentioned as a cause
      of candidiasis. The objective of this study is to ascertain whether or not
      tetracycline treatment can accelerate early-onset of C. albicans infection and
      the proliferative changes in this diabetic model. Alloxan-induced diabetic rats
      were given chlorinated water (AL group) and tetracycline solution (0.1% during
      week 1 and 0.01% thereafter) as drinking water (AT group). They were sacrificed
      after 25 weeks of drinking the treated water. The infection rate with C. albicans
      in the AT group was significantly higher than in the AL group. The incidence and
      severity of the squamous cell hyperplasia were enhanced in the AT group compared
      to the AL group. The proliferative lesions were consistently accompanied by
      inflammation and C. albicans infection in both groups. SCC was detected in one
      case in the AT group. These findings demonstrate that tetracycline induces C.
      albicans infection and enhances forestomach proliferative lesions in alloxan
      induced diabetic rats.

PMID- 22609948
TI  - Identification of a novel Wnt5a-CK1E-Dvl2-Plk1-mediated primary cilia disassembly
      pathway.
AB  - Non-motile primary cilium is an antenna-like structure whose defect is associated
      with a wide range of pathologies, including developmental disorders and cancer.
      Although mechanisms regulating cilia assembly have been extensively studied, how
      cilia disassembly is regulated remains poorly understood. Here, we report
      unexpected roles of Dishevelled 2 (Dvl2) and interphase polo-like kinase 1 (Plk1)
      in primary cilia disassembly. We demonstrated that Dvl2 is phosphorylated at S143
      and T224 in a manner that requires both non-canonical Wnt5a ligand and casein
      kinase 1 epsilon (CK1E), and that this event is critical to interact with Plk1 in
      early stages of the cell cycle. The resulting Dvl2-Plk1 complex mediated Wnt5a
      CK1E-Dvl2-dependent primary cilia disassembly by stabilizing the HEF1 scaffold
      and activating its associated Aurora-A (AurA), a kinase crucially required for
      primary cilia disassembly. Thus, via the formation of the Dvl2-Plk1 complex, Plk1
      plays an unanticipated role in primary cilia disassembly by linking Wnt5a-induced
      biochemical steps to HEF1/AurA-dependent cilia disassembly. This study may
      provide new insights into the mechanism underlying ciliary disassembly processes
      and various cilia-related disorders.

PMID- 22609950
TI  - Metabolic adaptive ALT isoenzyme response in livers of C57/BL6 mice treated with
      dexamethasone.
AB  - Alanine aminotransferase (ALT) is used as an indicator of hepatocellular injury.
      Since ALT consists of two isoenzymes, a better understanding of ALT isoenzyme
      biology in response to compounds that cause metabolic adaptive versus hepatotoxic
      responses will allow for a more accurate assessment of the significance of an ALT
      increase. The purpose of this study was to characterize the ALT isoenzyme
      response in mice treated with 25 or 75 mg/kg of dexamethasone, which is known to
      induce a progluconeogenic state, for 24 or 72 hr. Those mice treated with 75
      mg/kg for 72 hr showed an increase in total liver ALT activity. Western blot
      showed that there was an increase in ALT2 at both doses and time points and there
      was a concurrent increase in ALT2 ribonucleic acid at 24 and 72 hr. The ALT
      isoenzyme response assessed by an activity assay showed an increase in ALT2. The
      increases in liver ALT were associated with an increase in liver glycogen and
      there was no hepatocellular necrosis. There was an increase in total serum ALT
      activity, although serum isoenzymes were not evaluated. Thus, the authors
      demonstrated that dexamethasone induced increases in hepatic and serum ALT, which
      reflect a hepatocellular progluconeogenic metabolic adaptive response.

PMID- 22609951
TI  - Testicular development in cynomolgus monkeys.
AB  - The testes from 136 male cynomolgus monkeys were examined histopathologically in
      order to investigate the relationship between the development of spermatogenesis
      and testis weight, age, and body weight. At Grade 1 (immature), Sertoli cells and
      spermatogonia were the only cell classes in the testis. At Grade 2 (pre-puberty),
      no elongated spermatids were observed in the testis, although a few round
      spermatids and small lumen formation were observed. At Grade 3 (onset of
      puberty), all classes of germ cells were observed in the testis, although
      seminiferous tubule diameters and numbers of germ cells were small. Slight debris
      in the epididymis was observed in almost all animals. At Grade 4 (puberty),
      almost complete spermatogenesis was observed in the seminiferous tubules and it
      was possible to ascertain the spermatogenesis stage as described by Clermont,
      although tubule diameters and numbers of germ cells were small. There was less
      debris in the epididymis than at Grade 3. At Grade 5 (early adult), complete
      spermatogenesis was observed in the seminiferous tubules. At Grade 6 (adult),
      complete spermatogenesis in the seminiferous tubules and a moderate or large
      number of sperm in the epididymis were observed. Moreover, sperm analysis using
      ejaculated sperm was possible. Logistic regression analysis showed that testis
      weight is a good indicator of testicular maturity.

PMID- 22609952
TI  - Characterization of the biochemical properties of two methionine aminopeptidases
      of Cryptosporidium parvum.
AB  - We identified two methionine aminopeptidases of Cryptosporidium parvum (CpMetAP1
      and CpMetAP2) and characterized the biochemical properties of the recombinant
      enzymes. CpMetAP1 and CpMetAP2 belong to the type I and type II MetAP
      subfamilies, respectively. Both CpMetAPs have typical amino acid residues
      essential for metal binding and substrate binding sites, which are conserved in
      the MetAP family. Bacterially expressed recombinant CpMetAP1 and CpMetAP2 showed
      similar biochemical properties including a broad optimal pH range (pH 7.5-8.5)
      with maximum activity at pH 8.0. The two enzymes were stable under neutral and
      alkaline pHs but were relatively unstable under acidic conditions. The activities
      of CpMetAP1 and CpMetAP2 increased highly in the presence of Mn(2+) and Co(2+).
      CpMetAP1 and CpMetAP2 were effectively inhibited by the metal chelators, EDTA and
      1,10-phenanthroline, and were partially inhibited by the aminopeptidase
      inhibitors, amastatin and bestatin. Fumagillin also showed an inhibitory effect
      on both CpMetAPs.

PMID- 22609953
TI  - The first identification of Nymphicilichus perezae Mironov and Galloway, 2002 in
      cockatiels in Brazil and the first record of Psittophagus sp. Gaud and Atyeo,
      1996 and cf. Dubininia sp. Vassilev, 1958 in cockatiels (Nymphicus hollandicus
      Kerr, 1792).
AB  - Mite infestations were observed in 22 of 36 (61%) of Nymphicus hollandicus Kerr,
      1792 examined at the Wild Animal Sector of the Veterinary Medicine College -
      Universidade Federal Fluminense (UFF), Brazil. We examined 177 feather samples
      from 36 birds for ectosymbiotic arthropods. Nymphicilichus perezae Mironov and
      Galloway, 2002, was the predominant mite detected, followed by cf. Dubininia sp.
      Vassilev, 1958 (21.6%). Genus Psittophagus Gaud and Atyeo, 1996 were present in
      13.5% of samples. Concurrent infestations of N. perezae and cf. Dubininia sp.
      occurred in 22.7% of the cockatiels, of N. perezae and Psittophagus sp. in 9.1%,
      and of N. perezae, cf. Dubininia sp. and Psittophagus sp. in 4.6%. Results were
      analyzed through a descriptive analysis and the non-parametric Kruskal Wallis
      test was used to assess the distribution of mites among different regions of
      birds' bodies. This test showed that remiges primaries (right and left) were the
      feathers most infested. A few birds (9.1%) had feathers missing in some body
      regions. Feather-picking behavior was not observed during the clinical
      examination of the infested cockatiels, and no alterations in feather color were
      detected in the infestation foci. Due to their specificity to particular places
      on their hosts' different mite species, appear to live on the same bird without
      any apparent competition. This work is the first identification of N. perezae in
      the cockatiel N. hollandicus in Brazil. These are the first records of
      Psittophagus sp. and cf. Dubininia sp. in cockatiels.

PMID- 22609954
TI  - Echinococcus granulosus tegumental enzymes as in vitro markers of pharmacological
      damage: a biochemical and molecular approach.
AB  - Cystic echinococcosis is a chronic, complex, and neglected disease. Novel
      therapeutical tools are needed to optimize human treatment. A number of compounds
      have been investigated, either using in vitro cultured parasites and/or applying
      in vivo rodent models. Although some of these compounds showed promising
      activities in vitro, and to some extent also in the rodent models, they have not
      been translated into clinical applications. Membrane enzyme activities in culture
      supernatants of treated protoscoleces with calcium modulator drugs and
      anthelmintic drugs were measured and provided an indication of compound efficacy.
      This work describes for the first time the detection of alkaline phosphatase,
      gamma-glutamyl-transpeptidase and acetylcholinesterase activities in supernatants
      of in vitro treated Echinococcus granulosus protoscoleces. Marked differences on
      the enzymatic activities in supernatants from drug treated cultures were
      detected. We demonstrated that those genes that show the highest degree of
      conservation when compared to orthologs, are constitutively and highly expressed
      in protoscoleces and metacestodes. Due to high sensibility and the lack of
      activity in supernatants of intact protoscoleces, gamma-glutamyl-transpeptidase
      is proposed as the ideal viability marker during in vitro pharmacological studies
      against E. granulosus protoscoleces.

PMID- 22609955
TI  - Molecular identification of human echinococcosis in the Altai region of Russia.
AB  - Mitochondrial haplotypes were determined for Echinococcus species infecting
      individuals diagnosed with alveolar echinococcosis (AE) and cystic echinococcosis
      (CE) at Altai State Medical University Hospital in Barnaul, Russia during 2008 to
      2011. The nucleotide sequence of the mitochondrial cytochrome c oxidase subunit 1
      (cox1) gene was determined for 31 of 34 AE and 8 of 12 CE cases. All of the AE
      cases were confirmed to be caused by Asian type Echinococcus multilocularis,
      while CE cases were caused by Echinococcus granulosus sensu stricto (genotype G1)
      and Echinococcus canadensis (genotype G6).

PMID- 22609956
TI  - Ancestral modal Y-STR haplotype shared among Romani and South Indian populations.
AB  - One of the primary unanswered questions regarding the dispersal of Romani
      populations concerns the geographical region and/or the Indian caste/tribe that
      gave rise to the proto-Romani group. To shed light on this matter, 161 Y
      chromosomes from Roma, residing in two different provinces of Serbia, were
      analyzed. Our results indicate that the paternal gene pool of both groups is
      shaped by several strata, the most prominent of which, H1-M52, comprises almost
      half of each collection's patrilineages. The high frequency of M52 chromosomes in
      the two Roma populations examined may suggest that they descend from a single
      founder that has its origins in the Indian subcontinent. Moreover, when the Y-STR
      profiles of haplogroup H derived individuals in our Roma populations were
      compared to those typed in the South Indian emigrants from Malaysia and groups
      from Madras, Karnataka (Lingayat and Vokkaliga castes) and tribal Soligas,
      sharing of the two most common haplotypes was observed. These similarities
      suggest that South India may have been one of the contributors to the proto
      Romanis. European genetic signatures (i.e., haplogroups E1b1b1a1b-V13, G2a-P15, I
      M258, J2-M172 and R1-M173), on the other hand, were also detected in both groups,
      but at varying frequencies. The divergent European genetic signals in each
      collection are likely the result of differential gene flow and/or admixture with
      the European host populations but may also be attributed to dissimilar endogamous
      practices following the initial founder effect. Our data also support the notion
      that a number of haplogroups including G2a-P15, J2a3b-M67(xM92), I-M258 and
      E1b1b1-M35 were incorporated into the proto-Romani paternal lineages as migrants
      moved from northern India through Southwestern Asia, the Middle East and/or
      Anatolia into the Balkans.

PMID- 22609957
TI  - Reduced O2 concentration during CAM development--its effect on angiogenesis and
      gene expression in the broiler embryo CAM.
AB  - Hypoxia during embryogenesis may induce changes in the development of some
      physiological regulatory systems, thereby causing permanent phenotypic changes in
      the embryo. Various levels of hypoxia at different time points during
      embryogenesis were found to affect both anatomical and physiological
      morphogenesis. These changes and adaptations depended on the timing, intensity,
      and duration of the hypoxic exposure and, moreover, were regulated by
      differential expression of developmentally important genes, mostly expressed in a
      stage- and time-dependent manner. Eggs incubated in a 17%-oxygen atmosphere for
      12 h/d from E5 through E12 exhibited a clear and significant increase in the
      vascular area of the chorioallantoic membrane (CAM); an increase that was already
      significant within 12 h after the end of the 1st hypoxic exposures (E6). We used
      the combination of the genes, beta-actin, RPLP0 and HPRT as a reference for gene
      expression profiling, in studying the expression levels of hypoxia-inducible
      factor 1-alpha (HIF1alpha), vascular endothelial growth factor alpha-2 (VEGF
      alpha 2), vascular endothelial growth factor receptor 2 (KDR), matrix
      metalloproteinase-2 (MMP2), and fibroblast growth factor 2 (FGF2), under normal
      and hypoxic conditions. In general, expression of all five investigated genes
      throughout the embryonic day of development had similar patterns of hypoxia
      induced alterations. In E5.5 embryos, expression of HIF1alpha, MMP2, VEGFalpha2,
      and KDR was significantly higher in hypoxic embryos than in controls. In E6
      embryos expression of HIF1alpha, VEGFalpha2, and FGF2 was significantly higher in
      hypoxic embryos than in controls. From E6.5 onward expression levels of the
      examined genes did not show any differences between hypoxic and control embryos.
      It can be concluded that in this experimental model, exposing broiler embryos to
      17% O(2) from E5 to E7 induced significant angiogenesis, as expressed by the
      above genes. Further studies to examine whether this early exposure to hypoxic
      condition affects the chick's ability to withstand a post-hatch hypoxic
      environment is still required.

PMID- 22609959
TI  - Tracking artificial sweeteners and pharmaceuticals introduced into urban
      groundwater by leaking sewer networks.
AB  - There is little quantitative information on the temporal trends of
      pharmaceuticals and other emerging compounds, including artificial sweeteners, in
      urban groundwater and their suitability as tracers to inform urban water
      management. In this study, pharmaceuticals and artificial sweeteners were
      monitored over 6 years in a shallow urban groundwater body along with a range of
      conventional sewage tracers in a network of observation wells that were
      specifically constructed to assess sewer leakage. Out of the 71 substances
      screened, 24 were detected at above the analytical detection limit. The most
      frequent compounds were the iodinated X-ray contrast medium amidotrizoic acid
      (35.3%), the anticonvulsant carbamazepine (33.3%) and the artificial sweetener
      acesulfame (27.5%), while all other substances occurred in less than 10% of the
      screened wells. The results from the group of specifically constructed focus
      wells within 10 m of defective sewers confirmed sewer leaks as being a major
      entrance pathway into the groundwater. The spatial distribution of
      pharmaceuticals and artificial sweeteners corresponds well with predictions by
      pipeline leakage models, which operate on optical sewer condition monitoring data
      and hydraulic information. Correlations between the concentrations of
      carbamazepine, iodinated X-ray contrast media and artificial sweeteners were weak
      to non-existent. Peak concentrations of up to 4130 ng/l of amidotrizoic acid were
      found in the groundwater downstream of the local hospital. The analysis of 168
      samples for amidotrizoic acid, taken at 5 different occasions, did not show
      significant temporal trends for the years 2002-2008, despite changed
      recommendations in the medical usage of amidotrizoic acid. The detailed results
      show that the current mass balance approaches for urban groundwater bodies must
      be adapted to reflect the spatially distributed leaks and the variable wastewater
      composition in addition to the lateral and horizontal groundwater fluxes.

PMID- 22609958
TI  - Effect of chemical amendments to dairy soiled water and time between application
      and rainfall on phosphorus and sediment losses in runoff.
AB  - Dairy soiled water (DSW) is a dilute, low nutrient effluent produced on Irish
      dairy farms through the regular washing down of milking parlours and holding
      areas. In Ireland, there is no closed period for the land application of DSW
      except where heavy rain is forecast within 48 h. Chemical amendments have the
      potential to decrease phosphorus (P) and suspended sediment (SS) loss from DSW
      applied to land. This study examined the impact of three time intervals (12, 24
      and 48 h) between DSW application and rainfall and five treatments (control,
      unamended DSW, and DSW amended with lime, alum or ferric chloride (FeCl(2))) on P
      and sediment losses from an intact grassland soil in runoff boxes. Rainfall was
      simulated at 10.5 +/- 1 mm h(-1). Phosphorus concentrations (1-1.6 mg L(-1)) in
      runoff from DSW application, while not quantitative measures of P loss to surface
      waters in the field, indicated the importance of incidental P losses and that the
      current 48 h restriction in Ireland is prudent. Unamended DSW application
      increased P loss by, on average, 71%, largely due to an increase in particulate
      phosphorus (PP) loss. All three amendments were effective in decreasing P and SS
      losses in runoff and, apart from the SS results for lime, were significantly
      different (p<0.05) to the control at at least one time point. Lime (a 64%
      reduction in total phosphorus (TP) in comparison with DSW only) was less
      effective than alum or FeCl(2), likely due to the lower solubility of CaCO(3) in
      water. Chemical amendment showed potential to decrease P losses from land
      application of DSW, but the efficacy of such amendments would need to be assessed
      in field trials and a cost-benefit analysis conducted to further examine whether
      they could be practically implemented on farms.

PMID- 22609960
TI  - MMPT as a reactive oxygen species generator induces apoptosis via the depletion
      of intracellular GSH contents in A549 cells.
AB  - MMPT, (5-[(4-methylphenyl)methylene]-2-(phenylamino)-4(5H)-thiazolone), a
      thiazolidin compound, was identified in our laboratory as a novel antineoplastic
      agent with a broad spectrum of antitumor activity against many human cancer
      cells. A previous study showed that MMPT inhibited cell growth, and induced
      apoptosis in H1792 cells. In this study, the antiproliferative activity of MMPT
      was investigated. The results showed that MMPT was able to inhibit A549 cell
      growth in a time- and dose-dependent manner by blocking cell cycle progression in
      the G2 phase and inducing apoptosis. MMPT induced DNA fragmentation and caspase
      activation in A549 cells, both of which are hallmarks of apoptosis. The apoptotic
      process was accompanied by the generation of reactive oxygen species, depletion
      of glutathione (GSH), and reduction the GSH/GSSG ratio, suggesting that MMPT may
      induce apoptosis in A549 cells through a reactive oxygen species dependent
      pathway. Treatment with a thiol antioxidant, NAC, showed the recovery of GSH
      depletion and the reduction of reactive oxygen species levels in MMPT-treated
      cells, which were accompanied by the inhibition of apoptosis. In contrast, L
      buthionine sulfoximine (BSO), a well-known inhibitor of GSH synthesis, aggravated
      GSH depletion and cell death in MMPT-treated cells. In conclusion, we have
      demonstrated that MMPT inhibits the growth of A549 cells by inducing a G2 arrest
      of the cell cycle and by triggering apoptosis accompanied with the depletion of
      GSH.

PMID- 22609961
TI  - A New Mechanism of Stabilization of Large Decahedral Nanoparticles.
AB  - The stability of decahedral shaped nanoparticles depends upon size. Ino and Marks
      introduced new mechanisms for the stabilization of decahedra nanoparticles which
      involves the faceting and the formation of surfaces different of {111}. These
      mechanisms have relevance for small size nanoparticles; however, they do not
      explain, thoroughly, how decahedral particles can grow up to 300 nm or more.
      Here, we report new mechanisms that help stabilize very large decahedral. With
      the use of aberration corrected scanning transmission electron microscopy, we
      observed the formation of high index facets, determined to be of the {511}
      family, on all five sides of the particles. Surface dislocations strings are also
      observed. In addition, surface reconstruction of the {001} surfaces can also be
      observed in two different orientation: with hexagonal strings along the [110] and
      along the [410] directions.

PMID- 22609962
TI  - Controlled synthesis and optical spectroscopy of lanthanide-doped KLaF4
      nanocrystals.
AB  - KLaF(4), as a good host matrix for trivalent lanthanide (Ln(3+)) ions to
      fabricate upconversion (UC) or downconversion (DC) phosphors, has been rarely
      reported. Herein, monodisperse (~10 nm) cubic-phase Ln(3+)-doped KLaF(4)
      nanocrystals (NCs) were synthesized via a facile thermal decomposition method.
      Upon excitation at 980 nm, UC luminescence properties of KLaF(4):Ln(3+)/Yb(3+)
      (Ln = Tm, Ho, Er) NCs were comprehensively surveyed. Particularly, after coating
      an inert KLaF(4) shell, the green and red UC luminescence intensity of
      KLaF(4):Er(3+)/Yb(3+) NCs was enhanced ~35 times, and the corresponding UC
      lifetimes of (4)S(3/2) and (4)F(9/2) levels of Er(3+) were observed significantly
      prolonged from 42 and 68 MUs in core-only NCs to 87 and 136 MUs in core/shell
      counterparts. Furthermore, intense DC luminescence was also achieved in
      Ce(3+)/Tb(3+) and Eu(3+) doped KLaF(4) NCs, with absolute quantum yields of 39.8%
      (Tb(3+)) and 17.3% (Eu(3+)). The luminescence lifetimes of (5)D(0) (Eu(3+)) and
      (5)D(4) (Tb(3+)) were determined to be 4.2 and 4.7 ms, respectively. Water
      soluble Ln(3+)-doped KLaF(4) NCs featuring excellent monodispersion, long
      luminescence lifetime, and high UC/DC efficiency may have versatile and promising
      applications as luminescent nano-biolabels.

PMID- 22609963
TI  - Diacylglycerol stimulates acrosomal exocytosis by feeding into a PKC- and PLD1
      dependent positive loop that continuously supplies phosphatidylinositol 4,5
      bisphosphate.
AB  - Acrosomal exocytosis involves a massive fusion between the outer acrosomal and
      the plasma membranes of the spermatozoon triggered by stimuli that open calcium
      channels at the plasma membrane. Diacylglycerol has been implicated in the
      activation of these calcium channels. Here we report that this lipid promotes the
      efflux of intraacrosomal calcium and triggers exocytosis in permeabilized human
      sperm, implying that diacylglycerol activates events downstream of the opening of
      plasma membrane channels. Furthermore, we show that calcium and diacylglycerol
      converge in a signaling pathway leading to the production of phosphatidylinositol
      4,5-bisphosphate (PIP(2)). Addition of diacylglycerol promotes the PKC-dependent
      activation of PLD1. Rescue experiments adding phosphatidic acid or PIP(2) and
      direct measurement of lipid production suggest that both PKC and PLD1 promote
      PIP(2) synthesis. Inhibition of different steps of the pathway was reverted by
      adenophostin, an agonist of IP(3)-sensitive calcium channels, indicating that
      PIP(2) is necessary to keep these channels opened. However, phosphatidic acid,
      PIP(2), or adenophostin could not trigger exocytosis by themselves, indicating
      that diacylglycerol must also activate another factor. We found that
      diacylglycerol and phorbol ester stimulate the accumulation of the GTP-bound form
      of Rab3A. Together our results indicate that diacylglycerol promotes acrosomal
      exocytosis by i) maintaining high levels of IP(3) - an effect that depends on a
      positive feedback loop leading to the production of PIP(2) - and ii) stimulating
      the activation of Rab3A, which in turn initiates a cascade of protein
      interactions leading to the assembly of SNARE complexes and membrane fusion.

PMID- 22609964
TI  - Testing amendments for remediation of military range contaminated soil.
AB  - Military range soils are often strongly contaminated with metals. Information on
      the effectiveness of remediation of these soils is scarce. We tested the
      effectiveness of compost and mineral treatments for remediation and revegetation
      of military range soil collected in Aberdeen, MD. The soil was barren due to zinc
      (Zn) phytotoxicity while lead (Pb) posed a substantial risk to soil biota,
      wildlife and humans through various pathways. Seven treatments were tested:
      untreated control, agricultural NPK fertilization, high phosphate fertilization
      plus agricultural rates of NK, CaCO(3), "Orgro" biosolid compost, "Orgro" +
      CaCO(3), "Orgro" + CaCO(3) + Mn sulfate. All compost treatments alleviated Zn
      phytotoxicity to tall fescue; however compost combined with liming reduced plant
      Zn content up to 158-162 mg kg(-1). Compost added with lime reduced Pb in-vitro
      bioaccessibility from 32.5 to 20.4% of total Pb and was the most effective among
      the tested treatments. The study revealed the effectiveness of biosolids compost
      and lime mixture in the rapid stabilization of metals and revegetation of
      military range contaminated soils. The persistence of the remediation needs to
      be, however, confirmed in the long-term field study.

PMID- 22609965
TI  - Treatment of wastewater from coffee bean processing in anaerobic fixed bed
      reactors with different support materials: performance and kinetic modeling.
AB  - An evaluation was performed of three upflow anaerobic fixed bed reactors for the
      treatment of wastewater from coffee bean processing (WCP). The supports used
      were: blast furnace cinders, polyurethane foam and crushed stone with porosities
      of 53, 95 and 48%, respectively. The testing of these 139.5 L reactors consisted
      of increasing the COD of the influent (978; 2401 and 4545 mg L(-1)), while
      maintaining the retention time of 1.3 days. For the maximum COD applied, the
      reactor filled with foam presented removals of 80% (non-filtered samples) and 83%
      (filtered samples). The greater performance of the reactor filled with foam is
      attributed to its porosity, which promoted greater collection of biomass. From
      the results, it could be concluded that the reactors presented satisfactory
      performance, especially when using the foam as a support. Furthermore, the
      modified Stover-Kincannon and second order for multicomponent substrate
      degradation models were successfully used to develop a model of the experimental
      data.

PMID- 22609966
TI  - Radio-decontamination efficacy and safety studies on optimized decontamination
      lotion formulation.
AB  - Objective of the present study was to optimize decontamination lotion and to
      evaluate its relative decontamination efficacy using three radio-isotopes
      (Technetium-99m, Iodine-131 and Thallium-201) as contaminants with varying length
      of contaminant exposure (0-1h). Experiments were performed on Sprague Dawley
      rat's intact skin and human tissue equivalent models. Rat's hair was removed by
      using depilator after trimming with scissors. Relative decontamination efficacy
      of the optimized lotion was investigated and compared with water as control.
      Static counts were recorded before and after decontamination using single photon
      emission computed tomography (SPECT). Measured decontamination efficacy (DE)
      values were analyzed using one way ANOVA and Student's t-test (p value<0.05) and
      were found statistically significant. Decontamination efficacy of the lotion was
      observed to be 90 +/- 5%, 80 +/- 2% and 85 +/- 2%, for the (131)I, (201)Tl and
      (99m)Tc radio-contaminants respectively on skin. Reduced contaminant removal was
      recorded for the skin which was cleaned by depilator (50-60%). Skin
      decontamination was found more efficacious for rat skin decontamination than the
      human tissue equivalent model. Decontamination efficacy of the lotion against
      (99m)Tc was recorded 70 +/- 15% at 0-1h on the tissue equivalent model. In vitro
      chelation efficacy of the lotion was also established by using the instant thin
      layer chromatography-slica gel (ITLC-SG) and >95% of (99m)Tc was recorded.
      Neither erythema nor edema was scored in the primary skin irritancy test visually
      observed for two weeks.

PMID- 22609967
TI  - The reliability and validity of radiographic measurements for determining the
      three-dimensional position of the talus in varus and valgus osteoarthritic
      ankles.
AB  - OBJECTIVE: To assess the most accurate radiographic method to determine talar
      three-dimensional position in varus and valgus osteoarthritic ankles, we
      evaluated the reliability and validity of different radiographic measurements.
      MATERIALS AND METHODS: Nine radiographic measurements were performed blindly on
      weight-bearing mortise, sagittal, and horizontal radiographs of 33 varus and 33
      valgus feet (63 patients). Intra- and interobserver reliability was determined
      with the intraclass coefficient (ICC). Discriminant validity of measurements
      between varus and valgus feet was assessed with effect size (ES). Convergent
      validity (Pearson's r) was evaluated by correlating measurements to the
      dichotomized varus and valgus groups. Obtained measurements in both groups were
      finally compared with each other and with 30 control feet. RESULTS: Reliability
      was excellent (ICC > 0.80) in all but two measurements. Whereas frontal plane
      validity was excellent (ES and r > 0.80), horizontal and sagittal measurements
      showed poor to moderate validity (ES and r between 0.00 and 0.60). Four
      measurements were significantly different among all groups (p < 0.05). Talar
      positional tendency was found towards dorsiflexion or endorotation in the varus
      group and towards plantarflexion or exorotation in the valgus group. The frontal
      tibiotalar surface angle, sagittal talocalcaneal inclination angle, and
      horizontal talometatarsal I angle showed the best reliability, validity, and
      difference among the groups. CONCLUSION: The frontal tibiotalar surface angle,
      sagittal talocalcaneal inclination angle, and horizontal talometatarsal I angle
      accurately determine talar three-dimensional radiographic position in weight
      bearing varus and valgus osteoarthritic ankles. Careful radiographic evaluation
      is important, as these deformities affect talar position in all three planes.

PMID- 22609968
TI  - Paleopathological findings in radiographs of ancient and modern Greek skulls.
AB  - OBJECTIVE: The skull, when portrayed radiologically, can be a useful tool in
      detecting signs of systemic diseases and results of pathological growth
      mechanisms. The aim of this study was therefore to examine, compare, and classify
      findings in cranial configuration of pathological origin, in modern and ancient
      skulls. MATERIALS AND METHODS: The material consists of 240 modern and 141
      ancient dry skulls. Three radiographs for each skull (lateral, anteroposterior,
      basilar) provide enough evidence for differential diagnoses. RESULTS: Cases of
      osteoporosis are among the interesting pathological findings. A prevalence of
      female modern skulls in those determined as osteoporotic skulls is noted. Special
      interest is placed on the area of the sella turcica and many variations,
      regarding the shape and texture, are recognized both in ancient and modern
      skulls. Malignancies and important causes of cranial destruction are identified
      in both skull collections. Diploid thickening and osteolytic areas appear
      commonly among ancient remains. Moreover, from the ancient skull collection, one
      case possibly recognizable as fibrous dysplasia is noted while another case with
      an unusual exostosis gives rise to many questions. CONCLUSIONS: Interpreted with
      caution, the results of the present study, which can serve as an approach of
      paleopathology and paleoradiology, indicate similarity trends in cranial
      configuration of pathologic origin in modern and ancient people. Radiography and
      cephalometry were the main diagnostic tools used to gather evidence and are
      evaluated as a quite appropriate method to examine anthropological material and
      assess the internal structure of skeletal remains since they are non-destructive
      techniques.

PMID- 22609969
TI  - Synthesis of micro-sized SnO2@carbon hollow spheres with enhanced lithium storage
      properties.
AB  - Uniform and stable micro-sized SnO(2) hollow spheres are prepared by templating
      against polystyrene microspheres. After being coated with a thin layer of
      amorphous carbon, the as-obtained SnO(2)@carbon hollow microspheres are shown to
      exhibit improved lithium storage properties, delivering a reversible capacity of
      570 mA h g(-1) after 50 cycles at a high current density of 400 mA g(-1).

PMID- 22609970
TI  - Prevalence of Cryptosporidium species in recreational versus non-recreational
      water sources.
AB  - Cryptosporidiosis, caused by the protozoan parasite Cryptosporidium, represents
      the major public health concern of water utilities in developed nations due to
      its small size, resistance to disinfection and ability to be shed in large
      numbers in faeces. In Australia, recreational access is not allowed on direct
      supply sources, however, in Western Australia, limited recreational access to
      drinking water catchments has been allowed, although only in the outer catchment.
      Recreational activities within 2 km of the drinking water body is prohibited. The
      present study compared the amount, prevalence and species of Cryptosporidium in
      recreational versus non-recreational water catchments in the south west of
      Western Australia (WA). Recreational water catchments, which allowed swimming and
      camping had a higher prevalence of Cryptosporidium and the majority of samples
      were the human-associated C. hominis. Non-recreational catchments had a lower
      prevalence and all the samples genotyped were C. parvum. Risk analysis identified
      increasing population as strongly correlated with an increase in the prevalence
      of Cryptosporidium in recreational catchments. This suggests that recreational
      access to drinking water catchments is a serious public health risk and
      government policy limiting activities to the outer catchment should be supported.

PMID- 22609972
TI  - Duplex evaluation following femoropopliteal angioplasty and stenting: criteria
      and utility of surveillance.
AB  - Surveillance following lower extremity bypass, carotid endarterectomy, and
      endovascular aortic aneurysm repair has become the standard of care at most
      institutions. Conversely, surveillance following lower extremity endovascular
      interventions is performed somewhat sporadically in part because the duplex
      criteria for recurrent stenoses have been ill defined. It appears that duplex
      surveillance after peripheral endovascular interventions, as with conventional
      bypass, is beneficial in identifying recurrent lesions which may preclude failure
      and occlusion. In-stent stenosis following superficial femoral artery angioplasty
      and stenting can be predicted by both peak systolic velocity and velocity ratio
      data as measured by duplex ultrasound. Duplex criteria have been defined to
      determine both >=50% in-stent stenosis and >=80% in-stent stenosis. Although not
      yet well studied, it appears that applying these criteria during routine
      surveillance may assist in preventing failure of endovascular interventions.

PMID- 22609971
TI  - Inferring gene regulatory logic from high-throughput measurements of thousands of
      systematically designed promoters.
AB  - Despite extensive research, our understanding of the rules according to which cis
      regulatory sequences are converted into gene expression is limited. We devised a
      method for obtaining parallel, highly accurate gene expression measurements from
      thousands of designed promoters and applied it to measure the effect of
      systematic changes in the location, number, orientation, affinity and
      organization of transcription-factor binding sites and nucleosome-disfavoring
      sequences. Our analyses reveal a clear relationship between expression and
      binding-site multiplicity, as well as dependencies of expression on the distance
      between transcription-factor binding sites and gene starts which are
      transcription-factor specific, including a striking ~10-bp periodic relationship
      between gene expression and binding-site location. We show how this approach can
      measure transcription-factor sequence specificities and the sensitivity of
      transcription-factor sites to the surrounding sequence context, and compare the
      activity of 75 yeast transcription factors. Our method can be used to study both
      cis and trans effects of genotype on transcriptional, post-transcriptional and
      translational control.

PMID- 22609973
TI  - Penetration of the iliac bone as a modified tunneling option for graft infection
      in the groin.
AB  - A graft infection is one of the most fatal complications after surgical treatment
      for arteriosclerosis obliterans. Although both redo arterial revascularization
      for limb salvage and prevention of recurrent infection are necessary for the
      treatment of an infected prosthetic graft, surgical strategy is extremely
      troublesome and challenging. We successfully performed the extra-anatomic bypass
      by penetrating an iliac bone, in 3 cases. The anterior aspect of iliac crest was
      exposed through pararectal retroperitoneal incision. The hole in the iliac bone
      can be easily made by an electric scalpel. In performing redo arterial
      revascularization for the prosthetic vascular graft infection, reconstructing the
      extra-anatomic bypass by penetrating an iliac bone is one of the most
      advantageous treatments. This surgical strategy can help to select the flexible
      bypassed route, isolate the infected site, and completely eradicate its area of
      infection for wound healing.

PMID- 22609974
TI  - Species-specific differences in biomarker responses in two ecologically different
      earthworms exposed to the insecticide dimethoate.
AB  - Earthworms ingest large amounts of soil and therefore are continuously exposed to
      contaminants through their alimentary surfaces. Additionally, several studies
      have shown that earthworm skin is a significant route of contaminant uptake as
      well. In order to determine effects of dimethoate, a broad-spectrum
      organophosphorous insecticide, two ecologically different earthworm species were
      used - Eisenia andrei and Octolasion lacteum. Although several studies used soil
      organisms to investigate the effects of dimethoate, none of these studies
      included investigations of dimethoate effects on biochemical biomarkers in
      earthworms. Earthworms were exposed to 0.001, 0.005, 0.01, 0.5 and 1 MUg/cm(2) of
      dimethoate for 24 h, and the activities of acetylcholinesterase,
      carboxylesterase, catalase and efflux pump were measured. In both earthworm
      species dimethoate caused significant inhibition of acetylcholinesterase and
      carboxylesterase activities, however in E. andrei an hormetic effect was evident.
      Efflux pump activity was inhibited only in E. andrei, and catalase activity was
      significantly inhibited in both earthworm species. Additionally, responses of
      earthworm acetylcholinesterase, carboxylesterase and catalase activity to
      dimethoate were examined through in vitro experiments. Comparison of responses
      between E. andrei and O. lacteum has shown significant differences, and E. andrei
      has proved to be less susceptible to dimethoate exposure.

PMID- 22609975
TI  - Gene expression of ribosomal protein mRNA in Chironomus riparius: effects of
      endocrine disruptor chemicals and antibiotics.
AB  - Ribosomal protein genes are essential for cellular development. To examine the
      effects of ribosomal protein genes under various cellular stress conditions in
      chironomids, ribosomal protein S3 (RpS3) and S6 (RpS6) cDNA from Chironomus
      riparius were characterized and their expression was analyzed during development.
      A comparative and phylogenetic study among different orders of insects was
      carried out by analysis of sequence databases. C. riparius RpS3 was highly
      conserved at the protein level and shared over 85% amino acid identity with
      homologous sequences from other insects. RpS6 also showed approximately 80% amino
      acid identity. The RpS3 and S6 transcripts were present during different
      developmental stages but were most abundant during the embryonic stage.
      Furthermore, expression of the previously reported ribosomal proteins RpL11, L13,
      and L15, as well as RpS3 and S6 was analyzed following exposure to various
      concentrations of three endocrine disruptor chemicals (EDCs), di(2-ethylhexyl)
      phthalate, bisphenol A, and 4-nonylphenol (4NP), and the veterinary antibiotics
      (VAs) fenbendazole, sulfathiazole, and lincomycin. Only RpS3 gene expression was
      up-regulated significantly in response to EDCs and fenbendazole. However, the C.
      riparius ribosomal proteins showed a limited response to cellular stress,
      following exposure to EDCs and VAs.

PMID- 22609976
TI  - Effect of depressive symptoms on perceived disability in patients with chronic
      shoulder pain.
AB  - BACKGROUND: Psychological distress may be an important determinant of perceived
      disability in patients with chronic musculoskeletal disorders. We evaluated the
      relationship between depressive symptoms and perceived disability in patients
      with chronic shoulder pain and quantified the contribution made by depression to
      perceived disability. METHODS: In this prospective study, 109 patients with
      chronic shoulder pain caused by degenerative or inflammatory disorders were
      evaluated using the Disability of Arm, Shoulder and Hand (DASH) questionnaire and
      the Center for Epidemiologic Studies-Depression (CES-D) Scale to determine
      relationships between depressive symptoms and perceived disability in patients
      with chronic shoulder pain. In addition, pain scores were evaluated using a
      visual analog scale (VAS) during activity, and range of motion (ROM) and
      abduction strength (strength) measurements were measured. Multivariate analyses
      of variance and regression modeling were used to assess the relative
      contributions made by depressive symptoms (CES-D) and other clinical parameters
      to patient-perceived disability (DASH). RESULTS: DASH scores were found to be
      moderately correlated (0.3 < r < 0.6) with ROM, strength, pain VAS and CES-D;
      DASH scores were more strongly correlated with CES-D scores than with pain VAS
      scores or range of motion (r = 0.58; p < 0.001, 0.37; p < 0.001, 0.32; p = 0.04
      respectively). Multiple stepwise regression analyses revealed that gender, ROM,
      pain VAS and CES-D scores independently predicted DASH score and accounted for 43
      % of the variance. CES-D score was found to be the strongest predictor of DASH
      score and accounted for 23 % of the variance. CONCLUSIONS: Degrees of depressive
      symptoms were found to be significantly associated with higher symptom scores and
      greater disability in patients with chronic shoulder pain. Although a large
      proportion of perceived disability remains unexplained, perceived disability in
      patients with chronic shoulder pain was found to be strongly influenced by
      depressive symptoms. TYPE OF STUDY/LEVEL OF EVIDENCE: Level 2, prospective cohort
      study, prognostic study.

PMID- 22609977
TI  - Genotoxicity assessment of Garcinia achachairu Rusby (Clusiaceae) extract in
      mammalian cells in vivo.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Garcinia achachairu Rusby (Clusiaceae) is
      popularly known as "achachairu", and is used in Bolivian folk medicine for its
      healing, digestive, and laxative properties, and in the treatment of gastritis,
      rheumatism and inflammation. Despite its widespread therapeutic use, there is a
      lack of data regarding its in vivo genotoxic effects. Therefore, in this study,
      we used the comet assay and the micronucleus test, respectively, to evaluate the
      possible genotoxic and clastogenic effects of Garcinia achachairu seed extract
      (GAE) on different cells of mice. MATERIAL AND METHODS: The GAE was administered
      by oral gavage at doses of 500, 1000 and 2000 mg/kg. For the analysis, the comet
      assay was performed on the leukocytes (collected 4 and 24 h after treatment),
      liver, bone marrow and testicular cells (collected 24 h after treatment), and the
      micronucleus test (MN) on bone marrow cells. Cytotoxicity was assessed by scoring
      200 consecutive polychromatic (PCE) and normochromatic (NCE) erythrocytes
      (PCE/NCE ratio). RESULTS AND CONCLUSION: The results showed that GAE did not
      induce significant DNA damage in leukocytes (4 h and 24 h samples), liver, bone
      marrow and testicular cells (24 h samples). GAE also did not show any significant
      increase in micronucleated polychromatic erythrocytes (MNPCEs) at the three
      tested doses. The PCE/NCE ratio indicated no cytotoxicity. Under our experimental
      conditions, the data obtained suggest that a single oral administration of G.
      achachairu extract does not cause genotoxicity and clastogenicity in different
      cells of mice.

PMID- 22609978
TI  - Investigation of asymmetric alcohol dehydrogenase (ADH) reduction of acetophenone
      derivatives: effect of charge density.
AB  - In an effort to study the effect of substituent groups of the substrate on the
      alcohol dehydrogenase (ADH) reductions of aryl-alkyl ketones, several derivatives
      of acetophenone have been evaluated against ADHs from Lactobacillus brevis (LB)
      and Thermoanaerobacter sp. (T). Interestingly, ketones with non-demanding
      (neutral) para-substituents were reduced to secondary alcohols by these enzymes
      in enantiomerically pure form whereas those with demanding (ionizable)
      substituents could not be reduced. The effect of substrate size, their solubility
      in the reaction medium, electron donating and withdrawing properties of the
      ligand and also the electronic charge density distribution on the substrate
      molecules have been studied and discussed in detail. From the results, it is
      observed that the electronic charge distribution in the substrate molecules is
      influencing the orientation of the substrate in the active site of the enzyme and
      hence the ability to reduce the substrate.

PMID- 22609979
TI  - Thoracoscopic coaxial cutting needle biopsy for clinically suspected lung cancer:
      technical details, diagnostic accuracy, and probable complications.
AB  - BACKGROUND: Little has been described regarding the technical details, diagnostic
      accuracy, and probable complications of thoracoscopic cutting needle biopsy,
      which seems to be preferable to transthoracic needle biopsy for patients
      scheduled to undergo surgery for suspected lung cancer. METHODS: This study was a
      retrospective analysis of a prospective database of patients who underwent
      surgical biopsy for suspected lung cancer (n = 176). Sixty-two patients underwent
      thoracoscopic cutting needle biopsy, which was performed via thoracoport using a
      16 gauge coaxial cutting needle; the remaining 114 patients underwent excisional
      biopsy, followed by curative intent surgery. RESULTS: The sensitivity and
      specificity of diagnosing lung cancer by thoracoscopic needle biopsy were 57/59
      (96.6%) and 1/3 (33.3%), respectively. One false-negative result and one
      undiagnostic result occurred, but both lesions were correctly re-diagnosed by
      backup excisional biopsy during the same operation. When analysis was restricted
      to patients with lung lesions predominantly presenting with ground glass opacity,
      the sensitivity and specificity were 13/14 (92.9%) and 1/1 (100%), respectively.
      The sensitivity, specificity, and accuracy of diagnosing lung cancer by surgical
      biopsy in all patients were 164/165 (99.4%), 9/11 (81.8%), and 173/176 (98.3%),
      respectively. Pleural recurrence was identified in one patient after
      thoracoscopic needle biopsy whose pleural lavage cytology, performed before
      biopsy, was negative. CONCLUSIONS: Thoracoscopic cutting needle biopsy can be
      effectively applied to patients with an indeterminate lung tumor, especially
      those patients with lesions possessing ground glass opacity. However, further
      evaluation is necessary to confirm the risk of pleural dissemination induced by
      this procedure.

PMID- 22609980
TI  - Cryorecanalization: keys to success.
AB  - BACKGROUND: Symptomatic airway obstructions are common with endobronchial
      exophytic tumors and may result in lethal complications. Recently, a
      cryorecanalization procedure has emerged that plays a role in the immediate
      management of airway obstruction. This study was conducted to investigate the
      value of cryorecanalization for the immediate management of endobronchial
      obstructive pathology and to determine the factors that affect the success of the
      procedure. METHODS: We analyzed 40 patients with symptoms of airway obstruction
      who were admitted to our hospital from 2006 to 2010. Patients with exophytic
      stenosis due to primary bronchial or metastatic neoplasms who underwent
      cryorecanalization procedures were included. Patients were excluded if they had
      involvement of a major artery near the site of the intervention. The procedure
      was not performed on patients with coagulation abnormalities or thrombocyte count
      and aggregation problems. The data were collected retrospectively. RESULTS:
      Successful cryorecanalization was achieved in 72.5 % of patients. We found that
      the success rate was mainly related to the presence of the distal involvement and
      the older age of obstruction. Restenosis rate was 17.2 %. [corrected] The mean
      survival time after the cryorecanalization procedure was 11 +/- 12.7 months. No
      complications occurred in 14 patients. No severe bleeding was observed for any
      patients, and moderate hemorrhaging occurred in ten patients, which was stopped
      with an argon plasma coagulator. We experienced no intraoperative mortality.
      CONCLUSIONS: Cryorecanalization is a successful and safe intervention for the
      immediate management of endobronchial stenosis. Appropriate patient selection and
      high success rates should be achieved after careful radiological assessments and
      with early management.

PMID- 22609981
TI  - Outcome and safety of self-expandable metallic stents for malignant colon
      obstruction: a Korean multicenter randomized prospective study.
AB  - BACKGROUND: Newly developed uncovered stents are designed to have varied radial
      force and high conformability to improve clinical outcome and safety. This study
      aimed to determine and compare the clinical outcome and safety of the Taewoong D
      type uncovered stent and the Boston Scientific Wallfex stent. METHODS: Patients
      with acute malignant colonic obstruction were treated with a colonic stent. For
      the purpose of palliation, patients were randomly allocated. For the purpose of
      bridging, the type of stent was determined by the discretion of the individual
      doctors. Technical and clinical success and complication occurrence were measured
      as primary outcomes. RESULTS: From 12 university hospitals, 123 patients with
      malignant colonic obstruction were enrolled. Of these 123 patients, 58 were
      treated with colonic stents for palliative purposes. The technical and clinical
      success rate was 100 % for both stents in the palliative group. Perforation
      occurred for one patient (3.6 %) in the Wallflex stent group (n = 28) on day 5
      and for no patients in the D-type stent group (n = 30). Two cases of migration
      occurred: one with the Wallflex stent and one with the D-type stent. Stent
      restenosis occurred for one patient with the Wallflex stent. Preoperative
      bridging stents were placed in 65 patients. The median time to surgery was 10
      days. The technical success rate was 93.4 %, and clinical success was achieved
      for 86.2 % of the patients. Perforation occurred for five patients: four with the
      Wallflex stent and one with the D-type stent. The efficacy and safety of the two
      stents did not differ statistically. CONCLUSIONS: The D-type colonic uncovered
      stent and the Wallflex colonic uncovered stent are effective and safe for both
      palliative and preoperative bridging therapy used to treat acute malignant
      colonic obstruction.

PMID- 22609982
TI  - Kidney safety during surgical pneumoperitoneum: an experimental study in rats.
AB  - BACKGROUND: Elevations of intraabdominal pressure during laparoscopic procedures
      may lead to oliguria or anuria in mammals. Despite this, previous research has
      not been able to confirm an associated kidney injury. This study aimed to
      investigate the occurrence of an early kidney lesion secondary to surgical
      pneumoperitoneum in a rat model using the expression of neutrophil gelatinase
      associated lipocalin (N-GAL) as a biomarker for early kidney injury. METHODS: In
      this study, 20 male Sprague-Dawley rats under general anesthesia and mechanically
      ventilated were allocated to one of five experimental time-dependent groups:
      group 1 (1-h control), group 2 (1-h pneumoperitoneum), group 3 (2-h control),
      group 4 (2-h pneumoperitoneum), and group 5 (positive kidney injury group induced
      by intravenous administration of cisplatin 7.5 mg/kg). To evaluate the renal
      expression of N-GAL 24 h after the procedure, all the rats underwent a 2-h urine
      output evaluation as well as laparotomy and bilateral nephrectomy performed
      sequentially to investigate the presence of renal injury using immunofluorescence
      qualification and western blotting. RESULTS: Urine output was reduced and N-GAL
      expression was increased in the animals from the cisplatin group. The animals
      undergoing 1- or 2-h pneumoperitoneum displayed urine output and N-GAL expression
      similar to that of the animals from the matching control groups. CONCLUSIONS:
      Under the experimental conditions of this study, the animals with normal
      preoperative renal function did not show any type of acute kidney injury
      associated with the presence of a stabilized surgical pneumoperitoneum.

PMID- 22609983
TI  - Colorectal polyps: when should we tattoo?
AB  - BACKGROUND: Current guidelines recommend tattooing of suspicious-looking lesions
      at colonoscopy without a reference to the size of the polyp. However, the
      endoscopist has to make a judgement as to which lesion may be malignant and
      require future localisation based on the appearance and size of the polyp. The
      aim of this study was to determine the relationship between endoscopic polyp size
      and invasive colorectal cancer so as to inform tattooing practice for patients
      taking part in the national bowel cancer screening programme (BCSP). METHODS:
      Data of BCSP patients who had undergone a polypectomy between October 2008 and
      October 2010 were collected from a prospectively maintained hospital endoscopic
      database. Histology data were obtained from electronic patient records. RESULTS:
      A total of 165 patients had undergone 269 polypectomies. Their median age was 66
      years and 66 % were men. The mean endoscopic polyp size was 10.7 mm (SD = +/- 8
      mm). Histologically, 81 % were neoplastic with 95 % showing low-grade and 5 %
      high-grade dysplasia. Eight patients were found to have invasive malignancy
      within their polyp. The risk of invasive malignancy within a polyp was 0.7 %
      (1/143) when the endoscopic polyp size was <10 mm; the risk increased to 2.4 %
      (2/83) when the polyp size was 10-19 mm and 13 % (5/40) when the polyp was >20
      mm. This trend was statistically significant (p = 0.001). About 23 % of the
      patients had the site of their polyp tattooed; the mean size of the tattooed
      polyps was 21 mm (range = 15-50 mm). Consequently, 25 % of malignant polyps and
      63 % of polyps with high-grade dysplasia were not tattooed. CONCLUSION: The risk
      of polyp cancer among BCSP patients increases significantly when the endoscopic
      polyp size is >= 10 mm. We recommend that all polyps >= 10 mm be tattooed.

PMID- 22609985
TI  - Congested C2-symmetric aryliodanes based on an anti-dimethanoanthracene backbone.
AB  - A family of congested aryliodanes based on an anti-dimethanoanthracene backbone
      has been synthesised and two diaryliodonium salts and the iodyl derivative
      characterised by X-ray analysis. The latter shows a rare water coordination to
      the iodine(V) centre in the solid state. Applications of these reagents in
      functional group transfer reactions are reported.

PMID- 22609984
TI  - Perioperative management and treatment for complications during and after peroral
      endoscopic myotomy (POEM) for esophageal achalasia (EA) (data from 119 cases).
AB  - BACKGROUND: The aim of this study was to investigate the management and treatment
      for complications during and after peroral endoscopic myotomy (POEM) for patients
      suffering from esophageal achalasia (EA). METHODS: The data of 119 cases of EA
      patients who underwent POEM from October 2010 to July 2011 and the complications
      that arose during the operation, after the operation, and during follow-up were
      analyzed. RESULTS: Complications that occurred during the operation included
      cutaneous emphysema (22.7 %, 27/119) and pneumothorax (2.5 %, 3/119).
      Postoperative complications included pneumothorax (25.2 %, 30/119), subcutaneous
      emphysema (55.5 %, 66/119), mediastinal emphysema (29.4 %, 35/119), delayed
      hemorrhage (0.8 %, 1/119), pleural effusion (48.7 %, 58/119), minor inflammation
      or segmental atelectasis of the lungs (49.6 %, 59/119), and gas under diaphragm
      or aeroperitoneum (39.5 %, 47/119). Complications that occurred during follow-up
      included one case of difficulty eating caused by the stricture of mucosa and one
      case of dehiscence at the mouth of the tunnel created during surgery, with food
      retention. No deaths occurred. All complications were resolved through
      traditional treatment. No additional surgery was needed. CONCLUSION:
      Complications arising during and after POEM should be treated quickly and can be
      resolved by using traditional treatment. POEM can be expected to become the
      preferred treatment for EA.

PMID- 22609988
TI  - High-resolution ultrasonography in assessment of nail-related disorders.
AB  - OBJECTIVE: Disorders of the nail can pose a diagnostic challenge, and non
      invasive imaging is frequently required to clarify diagnosis and delineate
      anatomy pre-operatively. We explored the use of high-resolution ultrasonography
      in the assessment of patients with nail disorders attending orthopaedic hand
      clinics. METHODS: A search of a university teaching hospital musculoskeletal
      radiology database identified 36 patients (mean age 54.2 years) where
      ultrasonography was used to assess nail-related disorders between April 2003 and
      January 2007. Clinical, surgical and histological findings were correlated in
      these cases with ultrasound reports. RESULTS: Ultrasound findings correlated with
      the provisional diagnosis in 20 (61%) of 33 patients and provided a diagnosis in
      3 patients where a provisional diagnosis was unavailable. In 7 of the 13 cases
      where the clinical diagnosis differed from ultrasound findings, a lump originally
      diagnosed as cystic in origin was shown to be solid on ultrasound. Different nail
      pathologies showed different characteristics on ultrasonography, including
      differences in vascularity, echogenicity, changes in nail structure/shape and
      extension into the nail bed, matrix, fold or evidence of bony erosion. The
      ultrasound findings correlated with histological analysis and intra-operative
      assessment in 10 of 15 patients who underwent operative treatment. CONCLUSION:
      Ultrasound provides important information on the anatomy of the nail apparatus
      and can differentiate solid and cystic lesions. It can be used as a diagnostic
      tool and can therefore help in pre-operative planning of nail-related disorders.
      In our series ultrasound supported or improved upon the clinical diagnosis in 31
      (86%) out of the 36 patients presenting with nail-related disorders.

PMID- 22609986
TI  - PRR5L degradation promotes mTORC2-mediated PKC-delta phosphorylation and cell
      migration downstream of Galpha12.
AB  - Mammalian target of rapamycin complex 2 (mTORC2) phosphorylates AGC protein
      kinases including protein kinase C (PKC) and regulates cellular functions such as
      cell migration. However, its regulation remains poorly understood. Here we show
      that lysophosphatidic acid (LPA) induces two phases of PKC-delta hydrophobic
      motif phosphorylation. The late phase is mediated by Galpha(12), which
      specifically activates ARAF, leading to upregulation of the RFFL E3 ubiquitin
      ligase and subsequent ubiquitylation and degradation of the PRR5L subunit of
      mTORC2. Destabilization of PRR5L, a suppressor of mTORC2-mediated hydrophobic
      motif phosphorylation of PKC-delta, but not AKT, results in PKC-delta hydrophobic
      motif phosphorylation and activation. This Galpha(12)-mediated signalling pathway
      for mTORC2 regulation is critically important for fibroblast migration and
      pulmonary fibrosis development.

PMID- 22609989
TI  - Ultrasound-guided selective nerve root block versus fluoroscopy-guided
      transforaminal block for the treatment of radicular pain in the lower cervical
      spine: a randomized, blinded, controlled study.
AB  - OBJECTIVES: To compare the short-term effects and advantages of ultrasound-guided
      selective nerve root block with fluoroscopy-guided transforaminal epidural block
      for radicular pain in the lower cervical spine through assessment of pain relief,
      functional improvement, and safety. METHODS: A total of 120 patients with
      radicular pain from cervical spinal stenosis or cervical herniated disc were
      enrolled. All procedures were performed using a fluoroscopy or ultrasound
      apparatus. The subjects were randomly assigned to either the fluoroscopy (FL) or
      ultrasound (US) group. The complication frequencies during the procedures,
      treatment effects, and functional improvement of the nerve root block were
      compared at 2 and 12 weeks after the procedures. RESULTS: Verbal Numeric Pain
      Scale (VNS) improved 2 weeks and 12 weeks after the injections in both groups.
      Statistical differences were not observed in VNS, Neck Disability Index (NDI),
      and effectiveness between the groups. In 21 patients at US, vessels were
      identified at the anterior aspect of the foramen. Eleven patients had a critical
      vessel at the posterior aspect of the foramen and five patients had on artery
      continue medially into the foramen, forming, or joining a segmental feeder
      artery. In both cases, the vessels might well have been in the pathway of the
      needle correctly positioned under fluoroscopic guidance. Five cases of
      intravascular injections were observed only in FL without significant difference
      between the groups. CONCLUSIONS: The US-guided method may facilitate identifying
      critical vessels at unexpected locations relative to the intervertebral foramen
      and avoiding injury to such vessels, which is the leading cause of the reported
      complications from cervical transforaminal injections. On treatment effect, using
      either method of epidural injections to deliver steroids for cervical radicular
      pain, secondary to herniated intervertebral disc or foraminal stenosis,
      significant improvements in function and pain relief were observed in both groups
      after the intervention. However, significant difference was not observed between
      the groups. Therefore, the ultrasound-guided method was shown to be as effective
      as the fluoroscopy-guided method in pain relief and functional improvement, in
      addition to the absence of radiation and avoiding vessel injury at real-time
      imaging.

PMID- 22609990
TI  - Investigation of the antibiotic resistance and biofilm formation of
      Staphylococcus aureus strains isolated from gangrenous mastitis of ewes.
AB  - In this study, Staphylococcus aureus strains (n = 110) isolated from seven ewe
      flocks in Sanliurfa, Turkey were screened for antibiotic resistance and
      biofilmforming ability as well as for genes associated with antibiotic resistance
      and biofilm-forming ability. All isolates were found to be susceptible to
      oxacillin, gentamicin, clindamycin, cefoxitin, tetracycline, vancomycin,
      amoxicillin-clavulanic acid, ciprofloxacin and sulphamethoxazole-trimethoprim.
      The percent proportions of strains resistant to penicillin G, ampicillin and
      erythromycin were 27.2% (n = 30), 25.4% (n = 28) and 6.3% (n = 7), respectively.
      Regarding the antibiotic resistance genes, 32 (29%) isolates carried the blaZ and
      8 (7.2%) the ermC gene. Other resistance genes were not detected in the isolates.
      All isolates showed biofilm-forming ability on Congo red agar (CRA), while 108
      (98.18%) and 101 (91.81%) of them were identified as biofilm producers by the use
      of standard tube (ST) and microplate (MP) methods, respectively. All isolates
      carried the icaA and icaD genes but none of them harboured the bap gene. The
      results demonstrated that S. aureus isolates from gangrenous mastitis were mainly
      resistant to penicillins (which are susceptible to the staphylococcal beta
      lactamase enzyme), and less frequently to erythromycin. Furthermore, all of the
      S. aureus isolates produced biofilm which was considered a potential virulence
      factor in the pathogenesis of staphylococcal mastitis.

PMID- 22609991
TI  - Cholagogue-induced gallbladder emptying in the diagnosis of canine biliary
      obstruction.
AB  - The efficacy of ultrasound-guided cholagogue-induced gallbladder emptying for
      differentiating obstructive from non-obstructive hepatobiliary diseases was
      studied in icteric dogs. In 7 healthy Beagle dogs, Lipofundin 20% infusion (2
      ml/kg orally) evoked a vigorous gallbladder contraction of 44.2% (range: 35.3
      57.6%) and proved to be a useful, well-tolerable meal for routine use. In 24
      icteric dogs, gallbladder contraction was evoked by different cholagogues: the
      maximum reduction in gallbladder volume (%) for the three non-obstructive icteric
      dogs was 43.9% (range, 39.0-46.5%). The average gallbladder contraction of the 21
      dogs with biliary obstruction was less than 5%. In conclusion, the stimulation of
      gallbladder contraction with orally applied magnesium sulphate (MgSO4) or
      Lipofundin can be well demonstrated by ultrasound in dogs. The examination of
      cholagogue-induced gallbladder emptying is a valuable technique in icteric
      patients to indicate surgical intervention.

PMID- 22609992
TI  - Effect of enteral feeding on gallbladder function in dogs.
AB  - Nutritional support in critically ill patients is a fundamental principle of
      patient care. Little is known about gallbladder motility during the
      interdigestive phase and in response to enteral feeding. The objective of this
      study was to investigate the effect of enteral feeding on gallbladder function in
      dogs. The cholagogue meal (Lipofundin infusion) was applied in four anatomical
      positions (jejunum, duodenojejunal junction, descending duodenum, stomach) in
      five healthy Beagle dogs. Gallbladder volume (GBV) was monitored by
      ultrasonography. Lipofundin infusion given through the feeding tube caused a
      maximal gallbladder contraction of 9.2% (range 3.7-13.9%) in the jejunum, 16.5%
      (9.1-22.1%) at the duodenojejunal junction and 26.3% (22.8-29.5%) in the
      descending duodenum. When the cholagogue meal was given through the mouth, it
      caused a mean 33.8% (28.6-46.5%) maximum gallbladder contraction in the same
      animals. In conclusion, we can establish that the ultrasound-guided gallbladder
      emptying method proved to be a useful technique for monitoring the cholagogue
      effect of Lipofundin meal applied in different anatomical positions of the
      intestine. The deeper the position of application, the smaller and shorter
      gallbladder contraction was evoked.

PMID- 22609993
TI  - A rabbit model for studying degeneration and regeneration properties of young
      striated muscle at different distraction rates.
AB  - The present study evaluated the histological changes in the muscle tissue after
      limb lengthening in skeletally immature rabbits and assessed the effect of
      different lengthening rates on the regeneration and degeneration properties of
      striated muscle. Thirteen different lengthening protocols were applied on a total
      of 16 male domestic white rabbits divided into four groups. The histopathological
      changes were analysed by a semiquantitative method according to the scoring
      system of Lee et al. (1993). After evaluation of the five main degenerative
      parameters (muscle atrophy, internalisation of muscle nuclei, degeneration of the
      muscle fibre, perimysial and endomysial fibrosis, haematomas), it is evident that
      rabbits subjected to limb lengthening at a rate of 3.2 mm/day showed more
      degenerative changes than those limb-lengthened at 0.8 or 1.6 mm/day. Our study
      showed that the regenerative mechanisms were not endless. If the daily
      lengthening rate reached the 3.2 mm/day limit, the regenerating ability of the
      muscle decreased, and signs of degeneration increased significantly.

PMID- 22609994
TI  - Variation in the coding region of the prion protein gene in Slovak cattle.
AB  - This study was conducted to investigate the presence of single nucleotide
      polymorphisms (SNPs) in the coding region of the bovine prion protein (PrP) gene
      among healthy and bovine spongiform encephalopathy (BSE-) affected cattle in
      Slovakia. Denaturing gradient gel electrophoresis (DGGE) and single-strand
      conformation polymorphism (SSCP) followed by DNA sequencing were used to identify
      SNPs and variations in octapeptide repeats. Altogether three single nucleotide
      polymorphisms (g234a, c339t and c576t) and variations in the number of
      octapeptide repeat units (5 or 6) were found in the analysed part of the prion
      protein gene. All single nucleotide polymorphisms were silent, causing no amino
      acid changes. Significant differences (P < 0.05) in the genotype distribution of
      g234a polymorphism were observed when the homozygous genotype with a mutated
      allele (caa/caa) was compared to the heterozygous genotype -/cag among healthy
      and BSE-affected cattle. The homozygous genotype caa/caa was characteristic of
      the group of BSE-affected cattle. Additionally, the homozygous genotype caa/caa
      was significant for the group of Simmental crossbreeds among healthy cattle. The
      allele and genotype distribution of the other polymorphisms was not significantly
      different among groups of healthy and BSE-affected cattle. The possible influence
      of a silent mutation on expression of the gene is not clearly determined and
      needs further investigations.

PMID- 22609995
TI  - First report of a malignant collision skin tumour with malignant melanoma and
      anaplastic sarcoma components in a dog.
AB  - This paper describes the occurrence of a rare skin tumour that has been removed
      surgically from the upper lip of a 13-year-old Tibetan spaniel. The tumour was
      0.5 cm in diameter and macroscopically appeared as a single dermal mass, but
      histopathological analysis identified it as a biphasic collision mixed tumour. In
      the anatomically uniform tumour, 70% (4 mm in diameter) of the total parenchyma
      was formed by a high-grade sarcoma (with the presence of giant cells), and about
      30% of it (1 mm in diameter) was a malignant melanoma (again with the presence of
      giant cells). The histologically distinct, but anatomically uniform tumour parts
      were separated by a macroscopically invisible, non-neoplastic epithelial process
      originating from the overlying hyperplastic epidermis. The two malignant
      components did not infiltrate the peritumoural vessels and each other's
      substance. In the sarcoma part, the mitotic and apoptotic indexes were 32 and 8,
      respectively, whereas in the melanoma part the same parameters were 10 and 6,
      respectively. During the immunohistochemical investigations anti-alpha-SMA,
      anticytokeratin AE1-AE3, anti-Melan-A, anti-Ki-67 and anti-claudin-5 antibodies
      were applied. In conclusion, this is the first report of a primary cutaneous
      malignant biphasic collision mixed tumour formed by an anaplastic sarcoma with
      giant cells and a malignant melanoma.

PMID- 22609996
TI  - Mammary invasive micropapillary carcinoma in a male cat: Immunohistochemical
      description and clinical follow-up.
AB  - We describe the case of a 14-year-old Domestic Short Hair male cat that presented
      with a single mammary tumour one centimetre in diameter, classified as invasive
      micropapillary carcinoma. Histology and immunohistochemistry revealed a high
      mitotic index, a KI-67 index of 10%, a lack of reactivity to myoepithelial
      markers, and a dense infiltration with T and B lymphocytes at the periphery of
      the tumour. Micrometastases were detected in the regional lymph node at the time
      of surgery. Overall survival time was 10 months with a disease-free interval of
      7.5 months. Distant metastases in the sublumbar lymph nodes confirmed the
      aggressiveness of this tumour, which has recently been subtyped in female cats.
      This is the first case reported in male cats with a complete follow-up,
      highlighting the importance of prompt and aggressive treatment in the presence of
      mammary tumours in male cats.

PMID- 22609997
TI  - Ligand-induced changes in Oestrogen and thyroid hormone receptor expression in
      the developing rat cerebellum: A comparative quantitative PCR and Western blot
      study.
AB  - Oestrogen (E2) and thyroid hormones (THs) are key regulators of cerebellar
      development. Recent reports implicate a complex mechanism through which E2 and
      THs influence the expression levels of each other's receptors (ERs and TRs) to
      precisely mediate developmental signals and modulate signal strength. We examined
      the modulating effects of E2 and THs on the expression levels of their receptor
      mRNAs and proteins in cultured cerebellar cells obtained from 7-day-old rat pups.
      Cerebellar granule cell cultures were treated with either E2, THs or a
      combination of these hormones, and resulting receptor expression levels were
      determined by quantitative PCR and Western blot techniques. The results were
      compared to non-treated controls and to samples obtained from 14-day-old in situ
      cerebella. Additionally, we determined the glial effects on the regulation of ER
      TR expression levels. The results show that (i) ER and TR expression depends on
      the combined presence of E2 and THs; (ii) glial cells mediate the hormonal
      regulation of neuronal ER-TR expression and (iii) loss of tissue integrity
      results in characteristic changes in ER-TR expression levels. These observations
      suggest that both E2 and THs, in adequate amounts, are required for the precise
      orchestration of cerebellar development and that alterations in the ratio of
      E2/THs may influence signalling mechanisms involved in neurodevelopment.
      Comparison of data from in vitro and in situ samples revealed a shift in receptor
      expression levels after loss of tissue integrity, suggesting that such
      adjusting/regenerative mechanisms may function after cerebellar tissue injury as
      well.

PMID- 22609998
TI  - Are oestrogen receptors and protein tyrosine kinases involved in phytoestrogen
      modulated steroid secretion by porcine adrenocortical cells?
AB  - The phytoestrogens genistein and daidzein had been found to affect the function
      of some tissues via oestrogen receptors (ER). In addition, genistein, but not
      daidzein, is considered to be a protein tyrosine kinase (PTK) inhibitor. Thus,
      the involvement of oestrogen receptors and PTK in phytoestrogen action on
      adrenocortical porcine steroidogenesis was examined in this study. The aims of
      the experiment were to test the effects of (i) ICI 182, 780 (ICI), an ER
      antagonist, on genistein- and daidzein-modulated cortisol and androstenedione
      (A4) secretion by adrenocortical cells isolated during the luteal and follicular
      phases of the porcine oestrous cycle; (ii) tyrphostin AG 957 (TAG), a
      nonsteroidal PTK inhibitor, on cortisol and A4 secretion by the cells and (iii)
      the phase of the porcine oestrous cycle on the mechanism of phytoestrogen action.
      Adrenals were harvested during the luteal (n = 5 animals) and follicular (n = 5
      animals) phases of the oestrous cycle from locally slaughtered crossbred gilts.
      The isolated adrenocortical cells were incubated for 8 h (37  degrees C, 95% air,
      5% CO2) with genistein (5 or 10 MUM) or daidzein (5 or 10 MUM) in the presence or
      absence of ICI (0.5 MUM) or TAG (5 or 10 MUM). Genistein and daidzein inhibited
      cortisol secretion and stimulated A4 secretion by porcine adrenocortical cells
      harvested during both the luteal and follicular phases of the oestrous cycle. The
      ER antagonist ICI did not eliminate phytoestrogen-induced changes in
      steroidogenesis. In contrast to genistein, TAG reduced the secretion of A4 and
      did not affect cortisol secretion. There was no observable effect due to the
      phase of the cycle. It is suggested that the mechanism of genistein and daidzein
      action in the adrenocortical cells of pigs is independent of ER and PTK. It is
      possible that PTK are involved in A4 secretion by porcine adrenocortical cells.

PMID- 22609999
TI  - Accuracy for optical diagnosis of small colorectal polyps in nonacademic
      settings.
AB  - BACKGROUND & AIMS: When small colorectal lesions are accurately characterized,
      adenomas can be removed and discarded without formal histopathology analysis.
      Previous studies in an academic setting showed that many lesions can be managed
      accurately on the basis of their endoscopic image (optical diagnosis). We
      performed a prospective study to assess the accuracy of optical diagnosis of
      small colorectal polyps in a nonacademic setting (the DISCOUNT trial) by using
      high-resolution endoscopy (HRE) and narrow-band imaging (NBI). METHODS: During
      colonoscopy, 1 of 3 nonacademic endoscopists characterized small lesions and
      declared whether this was done with low or high confidence. In cases of high
      confidence, the endoscopists decided whether lesions should be removed and
      discarded or whether they could be left in situ. A surveillance interval was then
      recommended on-site. RESULTS: Of 215 patients in the study, 108 were found to
      have 281 small lesions. Of these lesions, 231 were characterized with high
      confidence by using HRE or NBI; the level of corresponding sensitivity was 77.0%
      (95% confidence interval, 68.4-83.8), and specificity was 78.8% (95% confidence
      interval, 70.6-85.2). Of these lesions, 164 were assigned for removal, and 67
      were assigned to remain in situ, including 9 adenomas. In 54 patients, a
      surveillance interval could be recommended on-site that was in line with Dutch
      guidelines for 44 patients. CONCLUSIONS: Even though many lesions were
      characterized by HRE or NBI with high confidence, optical diagnosis in a
      nonacademic setting proved to be disappointing, with a sensitivity of 77.0% and a
      specificity of 78.8%. Many lesions were accurately assigned to be removed or
      remain in situ, although few adenomas were assigned to remain in situ. Also, 19%
      of on-site recommendations for a surveillance interval proved to be inaccurate.

PMID- 22610001
TI  - Should we illuminate the black box of the small bowel mucosa from above or below?

PMID- 22610000
TI  - Increased bile acid biosynthesis is associated with irritable bowel syndrome with
      diarrhea.
AB  - BACKGROUND & AIMS: Variations in genes that regulate bile acid (BA) synthesis are
      associated with colonic transit in patients with irritable bowel syndrome (IBS).
      We investigated features of BA synthesis and excretion and genetic features of
      patients with different types of IBS. METHODS: In 26 healthy volunteers, 26
      patients with IBS and constipation (IBS-C), and 26 with IBS and diarrhea (IBS-D),
      we measured serum levels of 7alpha-hydroxy-4-cholesten-3-one (C4; a surrogate for
      BA synthesis) and fibroblast growth factor (FGF) 19 (an ileal hormone that
      downregulates BA synthesis). For stool samples, we measured concentration of BA,
      weight, and amount of fat when participants were given high-fat diets. Spearman
      correlations were used to explore relationships among factors. We analyzed 1
      polymorphism in Klotho-beta (KLB) and 3 in fibroblast growth factor receptor-4
      (FGFR4) for all members of each group using analysis of covariance. RESULTS: The
      concentration of BA in stool was associated with group (for a comparison of 3
      groups; P = .057); it was higher in patients with IBS-D than IBS-C (P = .017).
      The serum level of C4 was higher in patients with IBS-D than IBS-C (P = .02) or
      healthy volunteers (P = .01); 38% of patients with IBS-D had increased serum
      levels of C4, compared with healthy volunteers. Serum level of C4 correlated with
      stool concentration of BA (rs = 0.606; P < .001), serum FGF19 (rs = -0.324; P =
      .007), and stool weight (rs = 0.366; P = .003). Stool concentration of BA
      correlated with weight (rs = 0.737; P < .001) and level of fat (rs = 0.528; P <
      .001). Body mass index correlated with serum level of C4 (rs = 0.423, P < .001)
      and stool concentration of BA (rs = 0.507, P < .001), and was higher in patients
      with IBS-D compared with other groups (overall P = .036). FGFR4 rs1966265 was
      associated with stool level of BA (P = .032). CONCLUSIONS: Patients with IBS-D
      have greater body mass index and synthesize and excrete higher levels of BA than
      individuals with IBS-C or healthy volunteers. Serum levels of C4 might be used to
      identify patients with IBS-D who have BA malabsorption; studies are needed to
      determine if some patients have a genetic predisposition to this disorder.

PMID- 22610002
TI  - Prevalence and indicators of portal hypertension in patients with nonalcoholic
      fatty liver disease.
AB  - BACKGROUND & AIMS: Little is known about the prevalence and severity of portal
      hypertension in patients with nonalcoholic fatty liver disease (NAFLD). We
      investigated the prevalence and noninvasive predictors of portal hypertension in
      patients with NAFLD. METHODS: Signs of portal hypertension, including esophageal
      varices, splenomegaly, portosystemic encephalopathy, and ascites, were
      investigated in 354 patients with NAFLD. RESULTS: One hundred patients had portal
      hypertension at the time of NAFLD diagnosis (28.2%), 88 of these patients had
      septal fibrosis or cirrhosis (88%). Fibrosis stage correlated with presence (r =
      0.41, P < .0001) and number of findings (r = 0.48, P = .006) of portal
      hypertension. Of the 204 patients with no or mild fibrosis (stages, 0-2), 12
      patients had portal hypertension (6%); they had a significantly higher grade of
      steatosis, based on biopsy analysis, compared with the 192 patients without
      portal hypertension (94%). Thrombocytopenia, hyperbilirubinemia, cirrhosis, and
      obesity were associated independently with portal hypertension. Esophageal
      varices were found in 57 of the 128 patients undergoing endoscopic screening
      (44.5%) and were associated independently with thrombocytopenia, type 2 diabetes,
      and splenomegaly. CONCLUSIONS: Signs of portal hypertension were present in 25%
      of patients at the time of diagnosis of NAFLD; most had advanced fibrosis or
      cirrhosis. Portal hypertension can occur in a small proportion of patients with
      mild or no fibrosis and is associated with the extent of steatosis. Features of
      advanced liver disease and insulin resistance might identify patients with NAFLD
      and portal hypertension, and those expected to derive the most benefit from
      endoscopic screening for esophageal varices.

PMID- 22610004
TI  - Challenges in calculating the risk for colorectal cancer in patients with
      ulcerative colitis.

PMID- 22610003
TI  - The prevalence and diagnostic utility of endoscopic features of eosinophilic
      esophagitis: a meta-analysis.
AB  - BACKGROUND & AIMS: Endoscopic findings such as esophageal rings, strictures,
      narrow-caliber esophagus, linear furrows, white plaques, and pallor or decreased
      vasculature might indicate the presence of eosinophilic esophagitis (EoE). We
      aimed to determine the prevalence and diagnostic utility of endoscopic features
      of EoE. METHODS: We conducted a systematic review and meta-analysis. PubMed,
      EMBASE, and gastrointestinal meeting abstracts were searched to identify studies
      that included more than 10 patients with EoE and reported endoscopic findings.
      Pooled prevalence, sensitivity, specificity, and predictive values were
      calculated using random- and mixed-effects models. RESULTS: The search yielded
      100 articles and abstracts on 4678 patients with EoE and 2742 without (controls).
      In subjects with EoE, the overall pooled prevalence was as follows: esophageal
      rings, 44%; strictures, 21%; narrow-caliber esophagus, 9%; linear furrows, 48%;
      white plaques, 27%; and pallor/decreased vasculature, 41%. Substantial
      heterogeneity existed among studies. Results from endoscopy examinations were
      normal in 17% of patients, but this number decreased to 7% when the analysis was
      limited to prospective studies (P < .05). Overall levels of sensitivity were
      modest, ranging from 15% to 48%, whereas levels of specificity were greater,
      ranging from 90% to 95%. Positive predictive values ranged from 51% to 73% and
      negative predictive values ranged from 74% to 84%. CONCLUSIONS: There is
      heterogeneity among studies in the reported prevalence of endoscopic findings in
      patients with EoE, but in prospective studies at least 1 abnormality was detected
      by endoscopy in 93% of patients. The operating characteristics of endoscopic
      findings alone are inadequate for diagnosis of EoE. Esophageal biopsy specimens
      should be obtained from all patients with clinical features of EoE, regardless of
      the endoscopic appearance of the esophagus.

PMID- 22610005
TI  - Chronic inflammation, liver stiffness, and clinical decision making: an
      unavoidable partnership.

PMID- 22610006
TI  - Antegrade is more effective than retrograde enteroscopy for evaluation and
      management of suspected small-bowel disease.
AB  - BACKGROUND & AIMS: Antegrade and retrograde enteroscopy are useful for evaluating
      the proximal and distal small bowel, respectively. We compared the diagnostic
      yield, therapeutic yield, and complications of antegrade and retrograde
      enteroscopy. METHODS: We performed a retrospective review of a prospectively
      maintained database of patients who underwent small-bowel enteroscopy at our
      institution from January 2008 to August 2009. All enteroscopies were performed
      using single-balloon enteroscopy (SBE), double-balloon enteroscopy (DBE), or
      spiral enteroscopy (SE). A total of 250 enteroscopies were performed; 182 were
      antegrade (91 SBE, 52 DBE, and 39 SE) and 68 were retrograde (23 SBE, 37 DBE, and
      8 SE). The mean age of the patients was 61.5 +/- 15.8 years. RESULTS: The most
      common indication for small-bowel endoscopy was obscure gastrointestinal bleeding
      (n = 83). The diagnostic yield was significantly higher for antegrade than
      retrograde enteroscopy (63.7% vs 39.7%; P < .001). Antegrade procedures were of
      shorter duration than retrograde enteroscopy (44.3 +/- 22.0 vs 58.9 +/- 29.7 min;
      P < .001), and the mean depth of maximal insertion was significantly greater with
      antegrade endoscopy (231.8 +/- 122.1 vs 103.4 +/- 102.8 cm; P < .001). The
      therapeutic yield also was significantly higher for anterograde enteroscopy than
      retrograde enteroscopy (55.5% vs 44.1%; P < .001). There were no significant
      differences in complications. CONCLUSIONS: Antegrade enteroscopy appears to
      provide a higher diagnostic and therapeutic yield than retrograde enteroscopy in
      patients with suspected small-bowel disease.

PMID- 22610007
TI  - A 48-year-old woman with a new diagnosis of autoimmune hepatitis.

PMID- 22610008
TI  - Treatment of necrotizing pancreatitis.
AB  - Acute pancreatitis is a common and potentially lethal disease. It is associated
      with significant morbidity and consumes enormous health care resources. Over the
      last 2 decades, the treatment of acute pancreatitis has undergone fundamental
      changes based on new conceptual insights and evidence from clinical studies. The
      majority of patients with necrotizing pancreatitis have sterile necrosis, which
      can be successfully treated conservatively. Emphasis of conservative treatment is
      on supportive measures and prevention of infection of necrosis and other
      complications. Patients with infected necrosis generally need to undergo an
      intervention, which has shifted from primary open necrosectomy in an early
      disease stage to a step-up approach, starting with catheter drainage if needed,
      followed by minimally invasive surgical or endoscopic necrosectomy once
      peripancreatic collections have sufficiently demarcated. This review provides an
      overview of current standards for conservative and invasive treatment of
      necrotizing pancreatitis.

PMID- 22610009
TI  - Patients with celiac disease are not followed up adequately.
AB  - BACKGROUND & AIMS: Adherence to a gluten-free diet is the only effective
      treatment for celiac disease. It has been recommended that patients be followed
      up, make regular visits to the clinic, and undergo serologic analysis for markers
      of celiac disease, although a follow-up procedure has not been standardized. We
      determined how many patients with celiac disease are actually followed up.
      METHODS: We collected data on 122 patients with biopsy-proven celiac disease,
      diagnosed between 1996 and 2006 in Olmsted County, Minnesota (70% women; median
      age, 42 y), for whom complete medical records and verification of residency were
      available. We determined the frequency at which patients received follow-up
      examinations, from 6 months to 5 years after diagnosis. The Kaplan-Meier method
      was used to estimate event rates at 1 and 5 years. Patients were classified
      according to categories of follow-up procedures recommended by the American
      Gastroenterological Association (AGA). RESULTS: We estimated that by 1 and 5
      years after diagnosis with celiac disease, 41.0% and 88.7% of the patients had
      follow-up visits, 33.6% and 79.8% were assessed for compliance with a gluten-free
      diet, 3.3% and 15.8% met with a registered dietitian, 2.5% and 18.1% had an
      additional intestinal biopsy, and 22.1% and 65.6% received serologic testing for
      markers of celiac disease, respectively. Among 113 patients (93%) who were
      followed up for more than 4 years, only 35% received follow-up analyses that were
      consistent with AGA recommendations. CONCLUSIONS: Patients with celiac disease
      are not followed up consistently. Follow-up examinations often are inadequate and
      do not follow AGA recommendations. Improving follow-up strategies for patients
      with celiac disease could improve management of this disease.

PMID- 22610010
TI  - Cost utility of inflammation-targeted therapy for patients with ulcerative
      colitis.
AB  - BACKGROUND & AIMS: Oral mesalamine drugs are frequently used to treat patients
      with mild-to-moderate ulcerative colitis (UC). However, these drugs are costly,
      and long-term adherence is poor. We compared the cost utility of inflammation
      targeted, intermittent therapy with that of universal, continuous maintenance
      therapy with mesalamine agents for patients with mild-to-moderate UC. METHODS: We
      developed a Markov cohort model that simulated a population of adult patients
      with newly diagnosed, quiescent UC after induction of remission with mesalamine
      agents. We obtained model inputs from the literature. The perspective taken was
      that of a short-term payer (health insurance provider) during a 5-year time
      period. We modeled 3 treatment strategies: symptom-targeted treatment (treatment
      for symptomatic disease flares only, SYMPT), continuous mesalamine maintenance
      for all patients (CONT, the current standard of care), and inflammation-targeted
      treatment (mesalamine therapy for only patients with a stool sample positive for
      an inflammatory marker, INFLAM). We measured disease flares, quality-adjusted
      life years (QALYs), costs (2009 U.S. dollars), and incremental cost-effectiveness
      ratios. RESULTS: INFLAM was the least costly strategy (cumulative per-patient
      cost of $22,798), compared with $24,378 for the SYMPT and $25,621 for the CONT
      strategies. Despite the lower cost, INFLAM was comparable to SYMPT and CONT in
      effectiveness (4.4986 vs 4.5014 QALYs, respectively), making INFLAM the optimal
      strategy. Several variables were found to be important in sensitivity analysis;
      the CONT strategy was optimal only if the cost of mesalamine drugs was markedly
      reduced. CONCLUSIONS: Inflammation-targeted treatment of patients with UC is
      effective and costs less than continuous treatment of all patients with
      mesalamine, the current standard of care. Prospective trials of inflammation
      targeted treatment are warranted.

PMID- 22610014
TI  - FDA approves new ED remedy.

PMID- 22610013
TI  - Sinonasal outcome under aspirin desensitization following functional endoscopic
      sinus surgery in patients with aspirin triad.
AB  - Recalcitrant forms of recurrent nasal polyposis are problematic for patients as
      for rhinosurgeons. In aspirin-sensitive patients, aspirin desensitization is
      supposed to prevent recurrence by targeting the metabolism of arachidonic acid.
      Aspirin-sensitive patients (n = 65) following aspirin desensitization after
      functional endoscopic sinus surgery (FESS) for recurrent nasal polyposis under
      daily intake of 500-mg aspirin were compared to a post-FESS group (n = 81) of
      aspirin-sensitive individuals using exclusively topical mometasone. Quality of
      life (QoL) scores including sinonasal, pulmonal and general QoL items as well as
      endoscopic endonasal examination findings were evaluated during the postoperative
      follow-up period. After a follow-up period of minimum 18 months, a significant
      improvement in nasal obstruction, rhinorrhea, post nasal drip, sense of smell,
      facial pain, sleep quality and further general QoL items in desensitized patients
      was found compared to aspirin-sensitive controls. Improvement in sinonasal
      symptoms was evident, whereas the severity of asthmatic symptoms showed no
      significant changes. Although the pathophysiology of aspirin sensitivity is still
      not fully understood and the therapy is not sufficiently investigated, aspirin
      desensitization seems to have a positive effect on QoL scores concerning
      sinonasal symptoms and should be regarded as a possible postoperative treatment
      modality for recurrent nasal polyposis in aspirin-sensitive individuals.

PMID- 22610012
TI  - Sinonasal tumors: a clinicopathologic update of selected tumors.
AB  - The sinonasal cavities show a wide variety of neoplasms of epithelial,
      mesenchymal, neural/neuroectodermal or hematopoietic origin. The differential
      diagnosis for these tumors may be difficult due to overlapping morphologies,
      variable patterns in ancillary studies, and potentially confusing terminology. In
      this report, an updated review of the spectrum of neoplasia is provided, using
      the World Health Organization 2005 classification as a guide. Classic tumors that
      are generally limited to the sinonasal tract are described and new information
      regarding molecular pathogenesis is reviewed. Also new entities that have the
      sinonasal tract as a site of predilection, such as sinonasal renal cell-like
      adenocarcinoma and NUT midline carcinoma are highlighted.

PMID- 22610015
TI  - Osteoarthritis guidelines take balanced approach to therapy.

PMID- 22610016
TI  - Upcoming changes to Medicare Part D affect MTM services.

PMID- 22610017
TI  - GPhA to launch drug-shortage management program.

PMID- 22610018
TI  - Effect of standardized medication-order forms on medication errors after liver or
      kidney transplantation.

PMID- 22610019
TI  - Inadequate references in recent article.

PMID- 22610021
TI  - Caution in making inferences from FDA's Adverse Event Reporting System.

PMID- 22610022
TI  - On failures and rejections.

PMID- 22610023
TI  - Trust: an essential element of leaders and managers.

PMID- 22610024
TI  - Fidaxomicin: balancing evidence and economics.

PMID- 22610025
TI  - Fidaxomicin: a novel macrocyclic antibiotic for the treatment of Clostridium
      difficile infection.
AB  - PURPOSE: The pharmacology, clinical efficacy, safety, dosage and administration,
      and place in therapy of fidaxomicin for the treatment of Clostridium difficile
      infection (CDI) are reviewed. SUMMARY: Fidaxomicin, a macrocyclic antibiotic, has
      a narrow spectrum of activity against gram-positive anaerobes and is bactericidal
      against C. difficile. It has no activity against gram-negative bacteria.
      Fidaxomicin has minimal activity against Bacteroides species, which may be
      advantageous in maintaining colonization resistance and protecting the
      gastrointestinal tract from colonization by C. difficile. The minimum inhibitory
      concentration for 90% of organisms for fidaxomicin against C. difficile ranged
      from 0.0078 to 2 MUg/mL in in vitro studies. After oral administration, fecal
      concentrations are detected and are directly proportional to the dose
      administered. Fidaxomicin resistance in vivo has not been reported. In clinical
      trials, fidaxomicin has been shown to be noninferior to vancomycin in the
      management of mild-to-moderately severe CDI. The adverse-effect profile of
      fidaxomicin is comparable to that of vancomycin. The recommended dosage for
      treatment of CDI is fidaxomicin 200 mg orally twice daily for 10 days.
      Fidaxomicin should be considered for patients who previously received treatment
      with metronidazole or vancomycin for CDI and who are diagnosed with recurrent CDI
      in which a non-NAP1/BI/027 strain is isolated. At institutions where strain
      typing is not available, fidaxomicin may be considered in patients with recurrent
      CDI who have not responded to treatment with the regimen used for the first
      episode of CDI. CONCLUSION: Fidaxomicin is a well-tolerated agent for the
      treatment of CDI and has been shown to be noninferior to vancomycin in the
      management of mild-to-moderately severe CDI.

PMID- 22610026
TI  - Performance of a vancomycin dosage regimen developed for obese patients.
AB  - PURPOSE: An original and a revised vancomycin dosing protocol for obese patients
      were compared with respect to attainment of target serum trough vancomycin
      concentrations and the occurrence of nephrotoxicity. METHODS: The attainment of
      target vancomycin trough values (10-20 MUg/mL) and nephrotoxicity were compared
      retrospectively between an original protocol (vancomycin 15 mg/kg i.v. every 8-12
      hours), which had been associated with high troughs, and a revised protocol (10
      mg/kg i.v. every 12 hours or 15 mg/kg every 24 hours). Patients were included if
      they were obese (weight >= 100 kg and total body weight >= 140% of ideal body
      weight), had normal renal function (creatinine clearance >= 60 mL/min), had
      received i.v. vancomycin for at least 48 hours, and had one evaluable vancomycin
      trough value. Nephrotoxicity was defined as an increase in serum creatinine
      concentration of 0.5 mg/dL or of 50% over baseline, whichever was greater.
      RESULTS: Seventy-four and 64 patients were stratified into groups that had been
      treated with the revised and original protocols, respectively. The mean +/- S.D.
      maintenance dose was 19 +/- 2 mg/kg/day with the revised protocol and 34 +/- 7
      mg/kg/day with the original protocol (p < 0.001). Compared with the original
      protocol, the revised protocol resulted in a higher frequency of target troughs
      (59% versus 36%, p = 0.006) and below-target troughs (23% versus 9%, p = 0.033)
      and a lower frequency of above-target troughs (18% versus 55%, p < 0.001).
      Nephrotoxicity occurred in two patients in each group. CONCLUSION: Compared with
      the original vancomycin protocol for obese patients, a revised vancomycin
      protocol using lower total daily doses improved the attainment of target trough
      concentrations, with minimal nephrotoxicity.

PMID- 22610027
TI  - Oncology pharmacy practice as a model for international collaborations.

PMID- 22610028
TI  - Budget impact analysis of insulin therapies and associated delivery systems.
AB  - PURPOSE: A budget impact analysis of insulin therapies and associated delivery
      systems is presented. METHODS: Based on inputted procurement totals, per-item
      costs (based on 2011 average wholesale price), insulin distribution system (floor
      stock or individual patient supply), waste, and treatment protocols for a
      specified time frame, the budget impact model approximated the number of patients
      treated with subcutaneous insulin, costs, utilization, waste, and injection
      mechanism (pen safety needle or syringe) costs. To calculate net changes, results
      of one-year 3-mL vial use were subtracted from one-year 10-mL vial or 3-mL pen
      use. RESULTS: Switching from a 10-mL vial to a 3-mL vial was associated with
      reductions in both costs and waste. The net reductions in costs and waste ranged
      from $15,482 and 120,000 IU, respectively, for floor-stock 10-mL vial to floor
      stock 3-mL vial conversion to $871,548 and 6,750,000 IU, respectively, for
      individual patient supply 10-mL vial to floor-stock 3-mL vial conversion.
      Switching from floor-stock 10-mL vials to individual patient supply 3-mL vials
      increased costs and waste by $164,659 and 1,275,000 IU, respectively. Converting
      from individual patient supply 3-mL pens to individual patient supply 3-mL vials
      reduced costs by $117,236 but did not decrease waste. CONCLUSION: A budget impact
      analysis of the conversion of either 10-mL insulin vials or 3-mL insulin pens to
      3-mL insulin vials found reductions in both cost and waste, except when
      converting from floor-stock 10-mL vials to individual patient supply 3-mL vials.

PMID- 22610029
TI  - Analyzing methods for improved management of workflow in an outpatient pharmacy
      setting.
AB  - PURPOSE: The results of a workflow analysis at a large central outpatient
      pharmacy are reported, with theoretical modeling of potential efficiencies
      attainable through workflow enhancements. SUMMARY: In keeping with concepts of
      "lean health care," a time-motion analysis was conducted at a central outpatient
      pharmacy that dispenses an average of 250 prescriptions per day. Through direct
      observation over an eight-week period, pharmacists' dispensing-oriented
      activities were categorized as either value-added (i.e., centered on direct
      pharmacist-patient contact and, hence, providing increased value to the patient)
      or non-value-added. The workflow analysis suggested opportunities to derive more
      value from pharmacists' time by shifting their efforts away from non-value-added
      activities (i.e., technical dispensing functions) toward value-added activities:
      engagement of patients on entry into the pharmacy, pharmacist order verification,
      and patient counseling. The theoretical application of two models of enhanced
      workflow indicated that model A (expansion of pharmacy technicians' standard
      duties to include prescription preparation, stock-container retrieval, and
      prescription processing) could reduce pharmacists' non-value-added time by about
      55%, or more than six minutes per prescription, with an even greater (74%)
      potential reduction offered by model B (technician performance of checkout
      procedures in addition to expanded standard duties). Although the research site
      was atypical in its high staffing level relative to prescription volume, the
      findings suggest that similar workflow enhancements might be applicable in a
      range of community practice settings. CONCLUSION: Through analysis of existing
      workflow in an outpatient pharmacy, opportunities to optimize the use of value
      added pharmacist time in the dispensing process were identified.

PMID- 22610030
TI  - Health-system pharmacy's imperative for practice model change.

PMID- 22610031
TI  - Evaluation of a daptomycin dose-optimization protocol.
AB  - PURPOSE: The impact of an institutional protocol intended to improve daptomycin
      dosing for vancomycin-resistant enterococci (VRE) infections was investigated.
      SUMMARY: Daptomycin has been reported to have optimal activity against VRE at
      weight-based doses of >=8 mg/kg. As part of an initiative to optimize daptomycin
      dosing for all indications and regimens, a large medical center implemented a
      protocol restricting daptomycin prescribing to infectious-diseases specialists
      and a nomogram recommending elevated daptomycin dosing for all VRE infections,
      with baseline and weekly creatinine phosphokinase (CPK) determinations during
      daptomycin therapy. Protocol implementation was preceded by educational efforts
      targeting medical and pharmacy staff. A retrospective study was conducted to
      compare prescribing behavior and safety monitoring rates during the 12 months
      before and 16 months after protocol implementation; the baseline characteristics
      of the preimplementation cohort (n = 95) and postimplementation cohort (n = 72)
      were similar. The mean daptomycin doses before and after the protocol was
      implemented were 453 mg (6.1 mg/kg) and 576 mg (7.6 mg/kg), respectively. After
      protocol implementation, there were significant increases in the proportion of
      patients who received doses of >=8 mg/kg (52% in the postimplementation period
      versus 4% in the preimplementation period, p < 0.05) and in the rate of baseline
      CPK assessment (64% versus 43%, p < 0.05). CONCLUSION: Implementation of a
      daptomycin dosing protocol by a multidisciplinary antimicrobial stewardship team
      optimized treatment by increasing the mean dose of daptomycin administered to
      hospitalized adults with non-urinary VRE infections and improved the rate of
      safety monitoring.

PMID- 22610032
TI  - Pharyngeal odontoma in an adult walleye (Sander vitreus).
AB  - An adult walleye (Sander vitreus) was submitted to Cornell University for
      evaluation of a hard pale-tan pharyngeal mass attached to the gill arches. Dozens
      of hard white conical structures radiated from the surface. Microscopically,
      conical structures were identified as denticles and rested on plates of
      dysplastic orthodentine, cementum, and acellular bone. A diagnosis of compound
      odontoma was made based upon the presence of proliferative epithelial and
      mesenchymal odontogenic tissues that recapitulated tooth structures normally
      present on gill rakers. Odontomas are classified as hamartomas and typically
      develop in immature diphyodont mammals. The pharyngeal location and lifelong
      regeneration of teeth in fish, however, both qualify the present diagnosis in the
      pharyngeal region of an adult teleost. Ontogenic and morphologic differences
      between mammalian and piscine dentition and differentials for tooth-bearing
      tumors in fish are presented within the context of a developmental anomaly.

PMID- 22610033
TI  - Salient lesions in domestic ruminants infected with the emerging so-called
      Schmallenberg virus in Germany.
AB  - The so-called Schmallenberg virus (SBV), first detected in a German town of the
      same name in October 2011, is a novel emerging orthobunyavirus in Europe causing
      malformations and severe economic loss in ruminants. This report describes
      lesions in 40 sheep, 2 goats, and 16 cattle naturally infected with SBV as
      determined by real-time quantitative reverse transcription polymerase chain
      reaction. The most common macroscopic changes were arthrogryposis, vertebral
      malformations, brachygnathia inferior, and malformations of the central nervous
      system, including hydranencephaly, porencephaly, hydrocephalus, cerebellar
      hypoplasia, and micromyelia. Histologic lesions included lymphohistiocytic
      meningoencephalomyelitis in some cases, glial nodules mainly in the mesencephalon
      and hippocampus of lambs and goats, and neuronal degeneration and necrosis mainly
      in the brain stem of calves. Micromyelia was characterized by a loss of gray and
      white matter, with few neurons remaining in the ventral horn in calves. The
      skeletal muscles had myofibrillar hypoplasia in lambs and calves. The lesions of
      SBV-associated abortion and perinatal death are similar to those attributed to
      Akabane virus and other viruses in the Simbu group of bunyaviruses.

PMID- 22610034
TI  - Design and synthesis of a novel class of CK2 inhibitors: application of copper-
      and gold-catalysed cascade reactions for fused nitrogen heterocycles.
AB  - Two classes of fused nitrogen heterocycles were designed as CK2 inhibitor
      candidates on the basis of previous structure-activity relationship (SAR)
      studies. Various dipyrrolo[3,2-b:2',3'-e]pyridine and benzo[g]indazole
      derivatives were prepared using transition-metal-catalysed cascade and/or
      multicomponent reactions. Biological evaluation of these candidates revealed that
      benzo[g]indazole is a promising scaffold for potent CK2 inhibitors. The
      inhibitory activities on cell proliferation of these potent CK2 inhibitors are
      also presented.

PMID- 22610035
TI  - The identification of cutin synthase: formation of the plant polyester cutin.
AB  - A hydrophobic cuticle consisting of waxes and the polyester cutin covers the
      aerial epidermis of all land plants, providing essential protection from
      desiccation and other stresses. We have determined the enzymatic basis of cutin
      polymerization through characterization of a tomato extracellular
      acyltransferase, CD1, and its substrate, 2-mono(10,16
      dihydroxyhexadecanoyl)glycerol. CD1 has in vitro polyester synthesis activity and
      is required for cutin accumulation in vivo, indicating that it is a cutin
      synthase.

PMID- 22610036
TI  - Accumulation of dioxins and induction of cytochrome P450 1A4/1A5 enzyme
      activities in common cormorants from Lake Biwa, Japan: temporal trends and
      validation of national regulation on dioxins emission.
AB  - To validate the outcome of the national regulation on dioxins emission
      implemented in 1999, this study investigated temporal trends of chlorinated
      dioxins and related compounds (DRCs) in liver of common cormorants (Phalacrocorax
      carbo) collected from Lake Biwa, Japan between 2001 and 2008, as a part of the
      "Survey on the State of Dioxins Accumulation in Wildlife" conducted by the
      Ministry of the Environment, Japan. We also measured a biomarker of DRCs
      exposure, the cytochrome P450 1A (CYP1A)-dependent O-dealkylation activity of
      alkoxyresorufins (AROD), including methoxy-, ethoxy-, pentoxy- and benzyloxy
      resorufins in the samples over 2001-2007. Neither TEQ nor AROD activity showed
      any clear declining trend over the time period, although the emission of DRCs
      during the corresponding period was estimated to be apparently decreasing. Our
      data indicate that the concentration of recalcitrant DRCs in the cormorant during
      2001-2008 was scarcely affected by the national regulation on dioxins emission.

PMID- 22610037
TI  - Sorption mechanisms of perfluorinated compounds on carbon nanotubes.
AB  - Sorption of perfluorinated compounds (PFCs) on carbon nanotubes (CNTs) is
      critical for understanding their subsequent transport and fate in aqueous
      environments, but the sorption mechanisms remain largely unknown. In this study,
      the sorption of six PFCs on CNTs increased with increasing C-F chain length when
      they had a same functional group, and the CNTs with hydroxyl and carboxyl groups
      had much lower adsorbed amount than the pristine CNTs, indicating that
      hydrophobic interaction dominated the sorption of PFCs on the CNTs. Electrostatic
      repulsion suppressed the sorption of PFCs on the CNTs, resulting in the lower
      sorption with increasing pH. Hydrogen bonding interaction was negligible. The
      hydrophobic C-F chains can be closely adsorbed on the CNTs surface in parallel to
      the axis or along the curvature, making it impossible to form micelles on the CNT
      surface, leading to the lower sorption than other adsorbents.

PMID- 22610038
TI  - Biological effects of environmentally relevant concentrations of the
      pharmaceutical Triclosan in the marine mussel Perna perna (Linnaeus, 1758).
AB  - Triclosan (5-Chloro-2-(2,4-dichlorophenoxy) phenol) is an antibacterial compound
      widely employed in pharmaceuticals and personal care products. Although this
      emerging compound has been detected in aquatic environments, scarce information
      is found on the effects of Triclosan to marine organisms. The aim of this study
      was to evaluate the toxicity of a concentration range of Triclosan through
      fertilization assay (reproductive success), embryo-larval development assay
      (early life stage) and physiological stress (Neutral Red Retention Time assay -
      NRRT) (adult stage) in the marine sentinel organism Perna perna. The mean
      inhibition concentrations for fertilization (IC(50) = 0.490 mg L(-1)) and embryo
      larval development (IC(50) = 0.135 mg L(-1)) tests were above environmental
      relevant concentrations (ng L(-1)) given by previous studies. Differently,
      significant reduction on NRRT results was found at 12 ng L(-1), demonstrating the
      current risk of the continuous introduction of Triclosan into aquatic
      environments, and the need of ecotoxicological studies oriented by the mechanism
      of action of the compound.

PMID- 22610039
TI  - Distribution and bioavailability of cadmium in ornithogenic coral-sand sediments
      of the Xisha archipelago, South China Sea.
AB  - Total cadmium (Cd) concentrations in four ornithogenic coral-sand sedimentary
      profiles displayed a strong positive correlation with guano-derived phosphorus,
      but had no correlation with plant-originated organic matter in the top sediments.
      These results indicate that the total Cd distributions were predominantly
      controlled by guano input. Bioavailable Cd and zinc (Zn) had a greater input rate
      in the top sediments with respect to total Cd and total Zn, and a positive
      correlation with total organic carbon (TOC) derived from plant humus. Multi
      regression analysis showed that the total Cd and TOC explained over 80% of the
      variation of bioavailable Cd, suggesting that both guano and plant inputs could
      significantly influence the distribution of bioavailable Cd, and that plant
      biocycling processes contribute more to the recent increase of bioavailable Cd. A
      pollution assessment indicates that the Yongle archipelago is moderately to
      strongly polluted with guano-derived Cd.

PMID- 22610040
TI  - Ambulatory blood pressure monitoring and cardiac hypertrophy in children with
      metabolic syndrome.
AB  - BACKGROUND: The metabolic syndrome (MS), a cluster of potent risk factors for
      cardiovascular disease, is composed of insulin resistance, obesity, hypertension
      and hyperlipidemia. The aim of our study was to investigated the relationships
      between MS and left ventricular mass index (LVMI) in childhood MS. This study
      included 50 children and adolescents with MS aged between 7-18 years. METHODS:
      Thirty age- and sex-matched healthy children served as a control group. The
      diagnosis of MS was made according to the criteria adapted from the World Health
      Organization. They underwent clinical examination with causal blood pressure (BP)
      measurements, 24-hour ambulatory blood pressure monitoring (ABPM) and
      echocardiogram. Patients underwent echocardiography to detect left ventricular
      hypertrophy (LVH). LVMI was calculated as left ventricular mass/height(2.7).
      RESULTS: The mean age of MS group was 12.0 +/- 3.1 years. The mean value of LVMI
      was 46.5 +/- 11.5 g/m(2.7) in the MS group and it was significantly higher than
      those in the healthy children. The prevalence of severe LVH was 12 % using adult
      criteria (LVM > 51 g/m(2.7)) and 44 % using pediatric criteria (LVM > 95th
      percentile). The mean daytime systolic BP load (beta = 0.315, p = 0.003) and HOMA
      IR (beta = 0.368, p = 0.006) were found as the independent predictors of LVMI.
      CONCLUSIONS: In conclusion, LVH occurs commonly in pediatric MS and is associated
      with systolic hypertension and insulin resistance. LVMI should be measured
      routinely for the predicting of cardiovascular risks in these patients.

PMID- 22610041
TI  - Lymphoepithelial cyst of the pancreas: comparison of CT findings with other
      pancreatic cystic lesions.
AB  - OBJECTIVE: To describe the CT findings of lymphoepithelial cysts (LECs) of the
      pancreas and to investigate the differential findings between LECs and other
      pancreatic cystic lesions. MATERIALS AND METHODS: Fifty-eight patients with 8
      LECs (M:F = 7:1; mean age 55.1 years), 30 serous cystadenomas (SCA) (M:F = 11:19;
      52.5 years), 11 mucinous cystadenomas (MCA) (M:F = 0:11; 47.2 years), and 9
      pseudocysts (M:F = 6:3; 50.8 years) were included in this study. Two radiologists
      analyzed all CT images for 3D location, outer shape, appearance, the presence of
      calcification, enhancing nodule, and pancreatic duct dilatation. Size of lesions
      and CT number of cystic portion on precontrast CT were measured. For statistical
      analysis, Mann-Whitney U test and Fisher's exact test were used. RESULTS: 75 %
      (6/8) of LECs showed an extrapancreatic location than all other cystic diseases
      in terms of 3D location (p < 0.0001). LECs showed variable outer shape without a
      significant difference from that of SCAs and pseudocysts (p > 0.05), but LECs
      showed microlobulated surface more frequently than the MCAs (p < 0.05). LECs
      showed a variable appearance from unilocular to multi-microcystic. CT attenuation
      of LECs (21.2 +/- 7.1 HU) was higher than that of SCAs and MCAs (p = 0.005). Size
      of LECs (34.0 +/- 10.8 mm) was smaller than that of MCAs (p = 0.040). There was
      no calcification, pancreatic duct dilatation, or enhancing nodules in LECs.
      CONCLUSION: LECs appear as a highly exophytic medium-sized cystic mass with
      various morphology occurring predominantly in the middle-aged or older male
      patients.

PMID- 22610042
TI  - Intraperitoneal administration of Shiga toxin 2 induced neuronal alterations and
      reduced the expression levels of aquaporin 1 and aquaporin 4 in rat brain.
AB  - Shiga toxin-producing Escherichia coli produces watery and hemorrhagic diarrhea,
      and hemolytic uremic syndrome (HUS) characterized by thrombocytopenia,
      microangiopathic hemolytic anemia, and acute renal failure. Central nervous
      system (CNS) complications are observed in around 30% of infant population with
      HUS. Common signs of severe CNS involvement leading to death include seizures,
      alteration of consciousness, hemiparesis, visual disturbances, and brain stem
      symptoms. The purpose of the present work was to study the effects of Shiga toxin
      2 (Stx2) in the brain of rats intraperitoneally (i.p.) injected with a
      supernatant from recombinant E. coli expressing Stx2 (sStx2). Neurological
      alterations such as postural and motor abnormalities including lethargy, abnormal
      walking, and paralysis of hind legs, were observed in this experimental model of
      HUS in rats. Neuronal damage, as well as significant decrease in aquaporin 1
      (AQP1) and aquaporin 4 (AQP4) expression levels were observed in the brain of
      rats, 2 days after sStx2 injection, compared to controls. Downregulation of
      aquaporin protein levels, and neuronal alterations, observed in brain of rats
      injected with sStx2, may be involved in edema formation and in neurological
      manifestations characteristic of HUS.

PMID- 22610043
TI  - Carbapenem-hydrolyzing oxacillinase in high resistant strains of Acinetobacter
      baumannii isolated from India.
AB  - Acinetobacter baumannii, a Gram negative bacterium causes nosocomial infections
      including bacteremia, secondary meningitis and urinary tract infections.
      Increased resistance of A. baumannii has been global concern. Till recently,
      carbapenems, latest generation of beta-lactams are used for treating infections
      caused by A. baumannii. Emerging resistance to carbapenem class is an immediate
      threat to mankind. The objective of present study is to understand the growing
      carbapenem resistance of A. baumannii. By using iso-electric focusing followed by
      (in-gel) nitrocefin assay of carbapenem resistant strains of A. baumannii, we
      could identify three beta-lactamases with pIs in the range 5.4-9.5. Expression of
      the beta-lactamase with a pI ~ 8.5, was found only in very high carbapenem
      resistant (MIC for imipenem 128 MUg/ml) strains. On PCR analysis and sequencing
      of PCR product, this beta-lactamase was confirmed to be OXA-51. Identification of
      this protein from IEF gel was reconfirmed with the help of Liquid chromatography
      and Tandem mass spectrometry (LC-MS/MS). Based on the amino acid sequence, OXA-51
      found to be a 30 kDa beta-lactamase containing conserved functional motifs of
      class D serine beta-lactamase. In the present study, we have established the
      emergence of OXA-51 in clinical strains of A. baumannii in India which suggests
      its role in carbapenem resistance.

PMID- 22610044
TI  - Selection and evolutionary analysis in the nonstructural protein NSP2 of
      rotavirus A.
AB  - Rotavirus A is the leading cause of acute gastroenteritis in infants and young
      children worldwide. The nonstructural protein 2 (NSP2) plays essential roles in
      the replication cycle of rotavirus and may play a role in protective immunity
      against rotavirus disease. Using a Bayesian approach, we measured the mutation
      rate of genotype N1 NSP2 gene sequences. The N1 genotype is the main NSP2
      genotype associated with rotavirus strains causing severe disease, and was found
      to have a high mutation rate (8.7 * 10(-4) substitutions/site/year) in comparison
      to the rotavirus VP4 gene and rates of mutation in other RNA viruses. NSP2 has
      traditionally been considered as a conserved rotavirus protein and selection
      analysis indicated that the NSP2 protein was under strong negative selection,
      suggesting that most nucleotide substitutions were synonymous. This conservation
      is likely a result of functional constraints of NSP2 in the rotavirus replication
      cycle. Four sites of positive selection were identified; two of these (positions
      249 and 255) were located in a previously characterised antibody binding epitope.
      The remaining sites were not located in known functional regions, and the reason
      for variation at these sites remains to be elucidated.

PMID- 22610048
TI  - One-pass separation of single-wall carbon nanotubes by gel chromatography with a
      gradient of surfactant concentration.
AB  - We have investigated the diameter-selective separation of carbon nanotubes by one
      pass gel chromatography with a gradient of surfactant concentration. The
      formation of surfactant gradient in a column was successfully measured and is
      explained by a simple diffusion process even in the gel. We found that the
      diameter of eluted nanotubes is inversely proportional to the surfactant
      concentration of eluate. The detailed analysis of the movement of the nanotubes
      in the gel revealed that the separation mechanism was qualitatively explained by
      a model based on the trapping and de-trapping events of the nanotube-surfactant
      micelle on the gel surface,where the probability of the trapping and de-trapping
      events is proportional to the product of the diameter of the nanotubes and the
      surfactant concentration.

PMID- 22610045
TI  - Changes in cortical thickness in the frontal lobes in schizophrenia are a result
      of thinning of pyramidal cell layers.
AB  - Decreased cortical thickness and reduced activity as measured by fMRI in the grey
      matter of the subgenual cingulate cortex have been reported in schizophrenia and
      bipolar disorder, and cortical grey matter loss has been reliably reported in the
      frontal and temporal lobes in schizophrenia. The aim of this study was to examine
      the thickness of each of the six cortical layers in the subgenual cingulate
      cortex, five frontal lobe and four temporal lobe gyri. We examined two separate
      cohorts. Cohort 1 examines the subgenual cingulate cortex (SCC) in schizophrenia
      (n = 10), bipolar disorder (n = 15) and major depressive disorder (n = 20)
      against control subjects (n = 19). Cohort two examines frontal and temporal gyri
      in schizophrenia (n = 16), major depressive disorder (n = 6) against matched
      controls (n = 32). The cohorts were selected with identical clinical criteria,
      but underwent different tissue processing to contrast the effect of chemical
      treatment on tissue shrinkage. Measurements of layer I-VI thickness were taken
      from cresyl-violet- and haematoxylin-stained sections in cohort one and from
      cresyl-violet- and H&E-stained sections in cohort two. SCC cortical thickness
      decreased in male subjects with bipolar disorder (p = 0.048), and male
      schizophrenia cases showed a specific decrease in the absolute thickness of layer
      V (p = 0.003). Compared to controls, the relative thickness of layer V in the
      crown of the SCC decreased in schizophrenia (p < 0.001). A significant decrease
      in total cortical thickness was observed across the frontal lobe in schizophrenia
      (p < 0.0001), with specific pyramidal layer thinning in layers III (p = 0.0001)
      and V (p = 0.005). There was no effect of lateralization. No changes were noted
      in temporal lobe cortical thickness. This study demonstrates diminished pyramidal
      layer thickness resulting in decreased frontal lobe thickness in schizophrenia.

PMID- 22610050
TI  - Lesion of the isthmo-optic nucleus impairs target selection for visually guided
      reaching.
AB  - Neurons in the isthmo-optic nucleus (ION) of the avian midbrain receive input
      predominantly from the ipsilateral optic tectum and project to the contralateral
      retina. Therefore, lesion in the ION removes tectal efferent signals to the
      retina in birds. In the present study, we trained Japanese quail to reach a
      target stimulus on a touch-sensor monitor with their beak. ION lesions
      significantly decreased response accuracy when the target was presented
      simultaneously with distractors but not when presented alone. Thus the removal of
      the tectal efferent signals to the retina severely impaired target selection in a
      competitive visual search as if the ION-lesioning caused visual extinction, which
      is a neuropsychological deficit seen in human hemispatial neglect patients. We
      suggest that the avian tectum and its efferent path to the retina improve the
      accuracy of target selection for visual orienting and visually guided reaching
      with beak.

PMID- 22610049
TI  - Cycloheximide impairs and enhances memory depending on dose and footshock
      intensity.
AB  - This experiment examined the effects on memory of interactions of cycloheximide
      dose and training foot shock intensity. Mice received injections of cycloheximide
      (120 mg/kg, s.c.) or saline 30 min prior to inhibitory avoidance training with
      shock intensities of 100, 150, 250 or 300 MUA (1 s duration). Memory was tested
      48 h later. The saline control mice showed increasing memory latencies as a
      function of shock intensity. The ability of cycloheximide to impair memory
      increased as the training shock intensity increased. In a second experiment, mice
      were trained with a 200 MUA (1 s duration) shock and received injections of
      saline or cycloheximide at one of several doses (30, 60 or 120 mg/kg). Under
      these training conditions, cycloheximide enhanced memory in an inverted-U dose
      response manner. These findings are consistent with prior findings suggesting
      that protein synthesis inhibitors act on memory by altering modulators of memory
      formation as a secondary consequence of the inhibition of protein synthesis
      rather than by interfering with training-initiated synthesis of proteins required
      for memory formation.

PMID- 22610051
TI  - The protective effects of voluntary exercise against the behavioral consequences
      of uncontrollable stress persist despite an increase in anxiety following forced
      cessation of exercise.
AB  - Humans who exercise are less likely to suffer from stress-related mood disorders.
      Similarly, rats allowed voluntary access to running wheels have constrained
      corticosterone responses to mild stressors and are protected against several
      behavioral consequences of uncontrollable stress which resemble symptoms of human
      anxiety and depression, including exaggerated fear and deficits in shuttle box
      escape learning. Although exercise conveys clear stress resistance, the duration
      of time the protective effects of exercise against the behavioral consequences of
      uncontrollable stress persist following exercise cessation is unknown. The
      current studies investigated (1) whether exercise-induced stress resistance
      extends to social avoidance, another anxiety-like behavior elicited by
      uncontrollable stressor exposure, and (2) the duration of time the protective
      effects of exercise persist following forced cessation of exercise. Six weeks of
      wheel running constrained the increase in corticosterone elicited by social
      exploration testing, and prevented the reduction in social exploration,
      exaggerated shock-elicited fear, and deficits in escape learning produced by
      uncontrollable stress. The protective effect of voluntary exercise against stress
      induced interference with escape learning persisted for 15 days, but was lost by
      25 days, following cessation of exercise. An anxiogenic effect, as revealed by a
      reduction in social exploration and an increase in fear behavior immerged as a
      function of time following cessation of exercise. Results demonstrate that the
      protective effect of voluntary exercise against the behavioral consequences of
      uncontrollable stress extends to include social avoidance, and can persist for
      several days following exercise cessation despite an increase in anxiety produced
      by forced cessation of exercise.

PMID- 22610052
TI  - Chronic cannabinoid treatment during young adulthood induces sex-specific
      behavioural deficits in maternally separated rats.
AB  - A combination of early neurodevelopmental disruptions and young-adult cannabis
      use may lead to the development of neuropsychiatric disorders. The aim of this
      study was to investigate in adult Wistar rats (12-14 weeks of age) the long-term
      'two hit' behavioural effects of chronic young-adult treatment with the
      cannabinoid receptor agonist, CP55,940 (0.2 mg/kg, 8-10 weeks of age) in
      combination with maternal separation (MS) (3 h every day from postnatal days 2
      14). Two weeks after chronic CP55,940 treatment had ceased, baseline locomotor
      activity was reduced in male, but not female rats and irrespective of MS. In male
      rats only, the combination of MS and cannabinoid exposure, but not either 'hit'
      alone, induced a significant decrease in sucrose preference. In contrast, in male
      rats both MS and CP55,940 treatment reduced time spent on the open arms of the
      plus maze or centre time in the open field and this was most pronounced after a
      combination of these 'hits'. Prepulse inhibition was reduced by MS in both sexes
      but there was no additional effect of CP55,940 treatment. Memory performance in
      the Y-maze and novel object recognition test was not affected by either of the
      two 'hits'. These results indicate that early developmental disruptions and young
      adult cannabis use on their own or in combination can differentially and sex
      specifically affect behaviours related to neuropsychiatric disorders.

PMID- 22610053
TI  - High intake of folic acid or complex of B vitamins provides anti-Parkinsonism
      effect: no role for serum level of homocysteine.
AB  - Several lines of evidence show that homocysteine (Hcy) levels are increased in
      blood and CSF of patients with Parkinson's disease. B vitamins are necessary for
      Hcy metabolism and their deficiencies cause hyperhomocysteinemia and
      neurodegeneration. In present study, effect of B vitamin supplementation on the
      severity of 6-hydroxydopamine (6-OHDA)-induced Parkinsonism was investigated.
      Rats were nourished with B vitamin supplements from 1 month before of stereotaxic
      injection of 6-OHDA to the end of experiments. Total serum Hcy was measured at
      the end of experiments to identify its association with Parkinsonism. Both
      rotational and rotarod tests revealed that supplementation of folic acid, in a
      dose dependent manner, attenuates severity of Parkinsonism. Supplement of B
      complex also had beneficial effect and improved motor performance in rotarod test
      and decreased biased swings in elevated body swing test but had no effect on the
      apomorphine-induced rotational behavior. Supplement of B(6) attenuated rotational
      behavior but had no effect on the rotarod performance and swinging behavior.
      Supplement of B(12) or combination of folic acid with B(6) and B(12) had no
      effect on the behavioral symptoms of Parkinsonism. Except one group, the levels
      of Hcy in other vitamin B treated groups were near to that in control group.
      Surprisingly, Hcy in group of rats that received high intake of folic acid was
      significantly higher than that in control group. Our results indicate that high
      intake of folic acid or B complex provides anti-Parkinsonism effect but it is not
      mediated by lowering plasma Hcy.

PMID- 22610054
TI  - Aerobic fitness relates to learning on a virtual Morris Water Task and
      hippocampal volume in adolescents.
AB  - In rodents, exercise increases hippocampal neurogenesis and allows for better
      learning and memory performance on water maze tasks. While exercise has also been
      shown to be beneficial for the brain and behavior in humans, no study has
      examined how exercise impacts spatial learning using a directly translational
      water maze task, or if these relationships exist during adolescence--a
      developmental period which the animal literature has shown to be especially
      vulnerable to exercise effects. In this study, we investigated the influence of
      aerobic fitness on hippocampal size and subsequent learning and memory, including
      visuospatial memory using a human analogue of the Morris Water Task, in 34
      adolescents. Results showed that higher aerobic fitness predicted better learning
      on the virtual Morris Water Task and larger hippocampal volumes. No relationship
      between virtual Morris Water Task memory recall and aerobic fitness was detected.
      Aerobic fitness, however, did not relate to global brain volume or verbal
      learning, which might suggest some specificity of the influence of aerobic
      fitness on the adolescent brain. This study provides a direct translational
      approach to the existing animal literature on exercise, as well as adds to the
      sparse research that exists on how aerobic exercise impacts the developing human
      brain and memory.

PMID- 22610056
TI  - Monodisperse inorganic supraparticles: formation mechanism, properties and
      applications.
AB  - Monodisperse inorganic supraparticles (SPs) are an emerging and hot research
      topic in the chemistry, physics and materials science communities in the past
      several years. Monodisperse inorganic SPs exhibit unique physiochemical
      properties due to their well-defined shape and distinctive topological structure.
      This review summarizes recent progress in the study of formation mechanism,
      properties and applications of inorganic monodisperse SPs. The future
      developments in this research area are also discussed.

PMID- 22610055
TI  - Genetic polymorphisms influence the steroid treatment of children with idiopathic
      nephrotic syndrome.
AB  - BACKGROUND: Idiopathic nephrotic syndrome (INS) is the most frequent type of
      nephrotic syndrome that occurs in children. Its response to treatment with
      steroids varies. The aim of this study was to analyze the correlation between
      steroid metabolism-related genes and the response to steroid treatment. METHODS:
      The patient cohort comprised 74 children with INS, of whom were 58 steroid
      sensitive (SS) cases and 16 steroid-resistant (SR) cases. The genetic
      polymorphisms analyzed were those of the CYP3A5 gene (A6986G) and ABCB1 gene
      (C1236T, G2677T/A, and C3435T), and the polymorphisms between SS and SR children
      were compared. RESULTS: C1236T in ABCB1 was associated with steroid resistance in
      INS children [odds ratio (OR) 2.65, 95 % confidence interval (CI) 1.01-6.94; p =
      0.042] The frequency of the T allele was significantly higher in SR subjects than
      in SS subjects (0.81 vs. 0.62, respectively). A6986G in CYP3A5 showed a trend of
      association, but this association did not reach statistical significance (OR
      2.63, 95 % CI 0.94-7.37; p = 0.059). No significant correlation was found between
      treatment response and G2677T/A or C3435T in ABCB1. CONCLUSIONS: Our results
      indicate that among our pediatric patients with INS the C1236T polymorphism in
      the ABCB1 gene was associated with steroid resistance, while the A6986G
      polymorphism in the CYP3A5 gene showed a trend of association, but did not reach
      statistical significance, requiring further analysis.

PMID- 22610057
TI  - Hepatic adenomatosis: spectrum of imaging findings.
AB  - OBJECTIVE: This pictorial essay reviews the imaging appearance and differential
      diagnosis of hepatic adenomatosis. CONCLUSION: In addition to such entities as
      multifocal hepatocellular carcinoma, metastases, and multiple focal nodular
      hyperplasia, hepatic adenomatosis should also be considered when confronted with
      multiple hypervascular liver lesions. Certain CT and MRI features can strongly
      suggest the diagnosis of adenomatosis.

PMID- 22610058
TI  - Epithelioid angiomyolipoma of the liver: CT and MRI features.
AB  - The purpose of our study was to retrospectively evaluate the computed tomography
      (CT)/magnetic resonance imaging features of epithelioid angiomyolipoma of the
      liver (Epi-HAML), with pathology as a reference. We reviewed the CT/MRI findings
      of six lesions of Epi-HAML and found absence of adipose tissue in the lesions. In
      addition, recognizing the imaging features of no capsule, and hypervasularity
      with central punctiform or filiform vessels as a characteristic enhancement may
      distinguish Epi-HAML from other hepatic tumors.

PMID- 22610059
TI  - Supramolecular polymerization of oligopyrenotides--control by single, natural
      nucleotides.
AB  - Amphiphilic heptapyrenotides (Py(7)) assemble into supramolecular polymers. Here
      we present a comprehensive spectroscopic study of aggregates and co-aggregates of
      the non-chiral Py(7) and its mono- or di-substituted nucleotide analogs (Py(7)-N
      and N-Py(7)-N'). The data show that the formation of supramolecular polymers from
      oligopyrenotides is highly sensitive to the nature of the attached, chiral
      auxiliary. A single natural nucleotide may be sufficient for the fine tuning of
      the aggregates' properties by changing the mechanism of aggregation from an
      isodesmic to a nucleation-elongation process, which results in a high degree of
      amplification of chirality in the formed supramolecular polymers. Watson-Crick
      complementarity does not play a significant role, since co-aggregates of
      oligomers modified with complementary nucleotides show no signs of supramolecular
      polymerization. Depending on the nucleotide, the helical sense of the polymers is
      shifted to an M-helix or a P-helix. The findings demonstrate the value of
      oligopyrenotides as oligomeric building blocks for the generation of optically
      active supramolecular polymers.

PMID- 22610060
TI  - Ethnic Pride and Cardiovascular Health Among Mexican American Adults Along the
      U.S.-Mexico Border.
AB  - This study addressed the association between items from the General Acculturation
      Index (GAI) and cardiovascular health. Specifically, we assessed whether ethnic
      pride was associated with health outcomes after controlling for items regarding
      language, place where the childhood was spent and ethnic interaction. The study
      was a cross sectional analysis of demographic and clinical data from a border
      population of Mexican American adults (n=316) at risk for cardiovascular disease
      (CVD). Outcomes included smoking and diabetes status, Framingham risk, and
      metabolic syndrome. Ethnic pride was associated with lower diabetes prevalence,
      lower Framingham risk, and fewer risk factors for metabolic syndrome, but was not
      associated with smoking status. Ethnic pride was not associated with the other
      acculturation items of the GAI. Among an at-risk border population, ethnic pride
      functioned independently of other acculturation indicators. Ethnic pride may act
      as a protective factor for diabetes, metabolic syndrome and CVD risk status.

PMID- 22610061
TI  - Low-energy diaphyseal femoral fractures associated with bisphosphonate use and
      severe curved femur: a case series.
AB  - Recent reports have raised concerns about low-energy subtrochanteric and
      diaphyseal femoral fractures after long-term bisphosphonate treatment, which may
      be associated with severely suppressed bone turnover (SSBT). However, diaphyseal
      femoral fractures without bisphosphonate treatment have also been reported in
      patients with severely curved femur, which are commonplace in the elderly. The
      purpose of this study was therefore to investigate associations between
      occurrence of such fractures, bisphosphonate use, and curvature of the femur.
      Nine consecutive elderly patients treated for low-energy diaphyseal femoral
      fractures between 2005 and 2010 were retrospectively reviewed. Three patients
      sustained bilateral fractures. Eight patients were administered bisphosphonates
      and one patient was administered raloxifene. Duration of osteoporosis treatment,
      type of fractures, surgical procedure, cortical thickness and curvature of
      opposite femur were evaluated. The cortical thickness and femoral curvature were
      further compared with those of 24 control subjects without fractures. The mean
      duration of drug administration was 3.6 years. All fractures showed similar X-ray
      patterns of simple transverse fracture with medial spike. Only one femur showed
      thickening of the femoral cortex. One case was treated with locking plate
      fixation, while the other cases were operated with intramedullary nails (9
      antegrade nails, 2 retrograde nails). One femur treated with retrograde nail
      showed delayed bone union. The femoral curvature was significantly higher in the
      low-energy fracture group than the control group (P < 0.01); however, cortical
      thickness did not show a significant difference between the groups. In addition
      to SSBT, increased femoral curvature might be a causative factor for low-energy
      diaphyseal femoral fracture in the elderly.

PMID- 22610062
TI  - Salubrinal promotes healing of surgical wounds in rat femurs.
AB  - Phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha), transiently
      activated by various cellular stresses, is known to alleviate stress-induced
      cellular damage. Here, we addressed a question: does elevation of eIF2alpha
      phosphorylation by salubrinal (a pharmacological inhibitor of eIF2alpha
      dephosphorylation) enhance healing of bone wounds? We hypothesized that
      salubrinal would accelerate a closure of surgically generated bone holes by
      modifying expression of stress-sensitive genes. To examine this hypothesis, we
      employed a rat wound model. Surgical wounds were generated on anterior and
      posterior femoral cortexes, and salubrinal was locally administered on the
      anterior side. The results showed that, compared to a contralateral control, the
      size of surgical wounds was reduced by 10.8 % (day 10) and 18.0 % (day 20) on the
      anterior side (both p < 0.001), and 4.1 % (day 10; p < 0.05) and 11.1 % (day 20;
      p < 0.001) on the posterior side. In addition, salubrinal locally elevated
      cortical thickness and increased BMD and BMC. Pharmacokinetic analysis revealed
      that subcutaneous injection of salubrinal transiently increased its concentration
      in plasma followed by a rapid decrease within 24 h, and its half-life in plasma
      was 1.2 h. Salubrinal altered the phosphorylation level of eIF2alpha as well as
      the mRNA levels of ATF3, ATF4, and CHOP, and suppressed cell death induced by
      stress to the endoplasmic reticulum. In summary, the results herein demonstrate
      that subcutaneous administration of salubrinal accelerates healing of surgically
      generated bone holes through the modulation of eIF2alpha phosphorylation.

PMID- 22610063
TI  - Efficacy of intravenously administered ibandronate in postmenopausal Korean women
      with insufficient response to orally administered bisphosphonates.
AB  - We investigated rates of insufficient and over-responsiveness to orally
      administered bisphosphonates in postmenopausal women, and tested the efficacy of
      intravenous ibandronate in patients with insufficient response to orally
      administered bisphosphonates. Postmenopausal women were treated with either
      alendronate (70 mg/week; n = 88) or risedronate (35 mg/week; n = 84) for 1 year,
      and their response to orally administered bisphosphonates was assessed using
      serum C-telopeptide (CTX) levels. Insufficient responders were changed to once
      quarterly intravenous ibandronate 3 mg injection (n = 13) or maintained on orally
      administered bisphosphonates (n = 19), according to patients' preference, for an
      additional 1 year. There was no significant difference in baseline
      characteristics between two orally administered bisphosphonate groups except the
      bone mineral density values at the lumbar spine. Insufficient rate was higher in
      the risedronate group (19.0 %) than in the alendronate group (8.0 %), using the
      premenopausal serum CTX median as a cut-off (P = 0.043). The over-response rate
      among the alendronate group (59.1 %) was significantly higher than that in the
      risedronate group (38.1 %), based on a serum CTX cut-off value of 0.100 ng/ml (P
      = 0.006). Intravenous ibandronate suppressed serum CTX levels to a significantly
      greater degree at 7 days after the second dosing (0.191 +/- 0.110 ng/mL; P <
      0.001) and 3 months after the fourth dosing (0.274 +/- 0.159 ng/mL; P = 0.004)
      among insufficient responders, compared with post-oral/pre-intravenous levels
      (0.450 +/- 0.134 ng/mL). Rates of insufficient and over-responsiveness to orally
      administered bisphosphonates were considerable, and a change to intravenous
      bisphosphonates may be considered in patients showing an insufficient response to
      orally administered bisphosphonates.

PMID- 22610064
TI  - Comparing portable computers with bedside computers when administering
      medications using bedside medication verification.
AB  - This research examined bedside medication verification administration in 2 adult
      critical care units, using portable computers and permanent bedside computers.
      There were no differences in the number of near-miss errors, the time to
      administer the medications, or nurse perception of ease of medication
      administration, care of patients, or reliability of technology. The percentage of
      medications scanned was significantly higher with the use of permanent bedside
      computers, and nurses using permanent bedside computers were more likely to agree
      that the computer was always available.

PMID- 22610065
TI  - Mapping of lamin A- and progerin-interacting genome regions.
AB  - Mutations in the A-type lamins A and C, two major components of the nuclear
      lamina, cause a large group of phenotypically diverse diseases collectively
      referred to as laminopathies. These conditions often involve defects in chromatin
      organization. However, it is unclear whether A-type lamins interact with
      chromatin in vivo and whether aberrant chromatin-lamin interactions contribute to
      disease. Here, we have used an unbiased approach to comparatively map genome-wide
      interactions of gene promoters with lamin A and progerin, the mutated lamin A
      isoform responsible for the premature aging disorder Hutchinson-Gilford progeria
      syndrome (HGPS) in mouse cardiac myoytes and embryonic fibroblasts. We find that
      lamin A-associated genes are predominantly transcriptionally silent and that loss
      of lamin association leads to the relocation of peripherally localized genes, but
      not necessarily to their activation. We demonstrate that progerin induces global
      changes in chromatin organization by enhancing interactions with a specific
      subset of genes in addition to the identified lamin A-associated genes. These
      observations demonstrate disease-related changes in higher order genome
      organization in HGPS and provide novel insights into the role of lamin-chromatin
      interactions in chromatin organization.

PMID- 22610066
TI  - Effects and potential mechanisms of exercise training on cancer progression: a
      translational perspective.
AB  - Over the past decade there has been increasing research and clinical interest in
      the role of exercise therapy/rehabilitation as an adjunct therapy to improve
      symptom control and management following a cancer diagnosis. More recently, the
      field of 'exercise - oncology' has broadened in scope to investigate whether the
      benefits extend beyond symptom control to modulate cancer-specific outcomes
      (i.e., cancer progression and metastasis). Here we review the extant
      epidemiological evidence examining the association between exercise behavior,
      functional capacity/exercise capacity, and cancer-specific recurrence and
      mortality as well as all-cause mortality individuals following a cancer
      diagnosis. We also evaluate evidence from clinical studies investigating the
      effects of structured exercise on blood-based biomarkers associated with cancer
      progression/metastasis as well findings from preclinical investigations examining
      the effects and molecular mechanisms of exercise in mouse models of cancer.
      Current gaps in knowledge are also discussed.

PMID- 22610067
TI  - Early impact of social isolation and breast tumor progression in mice.
AB  - Evidence from cancer patients and animal models of cancer indicates that exposure
      to psychosocial stress can promote tumor growth and metastasis, but the pathways
      underlying stress-induced cancer pathogenesis are not fully understood. Social
      isolation has been shown to promote tumor progression. We examined the impact of
      social isolation on breast cancer pathogenesis in adult female severe combined
      immunodeficiency (SCID) mice using the human breast cancer cell line, MDA-MB-231,
      a high beta-adrenergic receptor (AR) expressing line. When group-adapted mice
      were transferred into single housing (social isolation) one week prior to MB-231
      tumor cell injection into a mammary fat pad (orthotopic), no alterations in tumor
      growth or metastasis were detected compared to group-housed mice. When social
      isolation was delayed until tumors were palpable, tumor growth was transiently
      increased in singly-housed mice. To determine if sympathetic nervous system
      activation was associated with increased tumor growth, spleen and tumor
      norepinephrine (NE) was measured after social isolation, in conjunction with
      tumor-promoting macrophage populations. Three days after transfer to single
      housing, spleen weight was transiently increased in tumor-bearing and non-tumor
      bearing mice in conjunction with reduced splenic NE concentration and elevated
      CD11b+Gr-1+ macrophages. At day 10 after social isolation, no changes in spleen
      CD11b+ populations or NE were detected in singly-housed mice. In the tumors,
      social isolation increased CD11b+Gr-1+, CD11b+Gr-1-, and F4/80+ macrophage
      populations, with no change in tumor NE. The results indicate that a
      psychological stressor, social isolation, elicits dynamic but transient effects
      on macrophage populations that may facilitate tumor growth. The transiency of the
      changes in peripheral NE suggest that homeostatic mechanisms may mitigate the
      impact of social isolation over time. Studies are underway to define the
      neuroendocrine mechanisms underlying the tumor-promoting effects of social
      isolation, and to determine the contributions of increased tumor macrophages to
      tumor pathogenesis.

PMID- 22610068
TI  - Hepatocyte growth factor mediates mesenchymal stem cell-induced recovery in
      multiple sclerosis models.
AB  - Mesenchymal stem cells (MSCs) have emerged as a potential therapy for a range of
      neural insults. In animal models of multiple sclerosis, an autoimmune disease
      that targets oligodendrocytes and myelin, treatment with human MSCs results in
      functional improvement that reflects both modulation of the immune response and
      myelin repair. Here we demonstrate that conditioned medium from human MSCs (MSC
      CM) reduces functional deficits in mouse MOG35-55-induced experimental autoimmune
      encephalomyelitis (EAE) and promotes the development of oligodendrocytes and
      neurons. Functional assays identified hepatocyte growth factor (HGF) and its
      primary receptor cMet as critical in MSC-stimulated recovery in EAE, neural cell
      development and remyelination. Active MSC-CM contained HGF, and exogenously
      supplied HGF promoted recovery in EAE, whereas cMet and antibodies to HGF blocked
      the functional recovery mediated by HGF and MSC-CM. Systemic treatment with HGF
      markedly accelerated remyelination in lysolecithin-induced rat dorsal spinal cord
      lesions and in slice cultures. Together these data strongly implicate HGF in
      mediating MSC-stimulated functional recovery in animal models of multiple
      sclerosis.

PMID- 22610070
TI  - Preparation and catalytic evaluation of ruthenium-nickel dendrimer encapsulated
      nanoparticles via intradendrimer redox displacement of nickel nanoparticles.
AB  - Ru and Ru(x)Ni(30) dendrimer encapsulated nanoparticles (DENs) were synthesized
      using a redox-displacement method. DEN catalytic activity for the reduction of p
      nitrophenol was evaluated and found to be dependent on the ratio of metals
      present.

PMID- 22610069
TI  - An unconventional role for miRNA: let-7 activates Toll-like receptor 7 and causes
      neurodegeneration.
AB  - Activation of innate immune receptors by host-derived factors exacerbates CNS
      damage, but the identity of these factors remains elusive. We uncovered an
      unconventional role for the microRNA let-7, a highly abundant regulator of gene
      expression in the CNS, in which extracellular let-7 activates the RNA-sensing
      Toll-like receptor (TLR) 7 and induces neurodegeneration through neuronal TLR7.
      Cerebrospinal fluid (CSF) from individuals with Alzheimer's disease contains
      increased amounts of let-7b, and extracellular introduction of let-7b into the
      CSF of wild-type mice by intrathecal injection resulted in neurodegeneration.
      Mice lacking TLR7 were resistant to this neurodegenerative effect, but this
      susceptibility to let-7 was restored in neurons transfected with TLR7 by
      intrauterine electroporation of Tlr7(-/-) fetuses. Our results suggest that
      microRNAs can function as signaling molecules and identify TLR7 as an essential
      element in a pathway that contributes to the spread of CNS damage.

PMID- 22610071
TI  - Polymorphisms in carcinogen metabolism enzymes, fish intake, and risk of prostate
      cancer.
AB  - Cooking fish at high temperature can produce potent carcinogens such as
      heterocyclic amines and polycyclic aromatic hydrocarbons. The effects of these
      carcinogens may undergo modification by the enzymes responsible for their
      detoxification and/or activation. In this study, we investigated genetic
      polymorphisms in nine carcinogen metabolism enzymes and their modifying effects
      on the association between white or dark fish consumption and prostate cancer
      (PCA) risk. We genotyped 497 localized and 936 advanced PCA cases and 760
      controls from the California Collaborative Case-Control Study of Prostate Cancer.
      Three polymorphisms, EPHX1 Tyr113His, CYP1B1 Leu432Val and GSTT1 null/present,
      were associated with localized PCA risk. The PTGS2 765 G/C polymorphism modified
      the association between white fish consumption and advanced PCA risk (interaction
      P 5 0.002), with high white fish consumption being positively associated with
      risk only among carriers of the C allele. This effect modification by PTGS2
      genotype was stronger when restricted to consumption of well-done white fish
      (interaction P 5 0.021). These findings support the hypotheses that changes in
      white fish brought upon by high-temperature cooking methods, such as carcinogen
      accumulation and/or fatty acid composition changes, may contribute to prostate
      carcinogenesis. However, the gene-diet interactions should be interpreted with
      caution given the limited sample size. Thus, our findings require further
      validation with additional studies.

PMID- 22610072
TI  - Release of TGFbetaig-h3 by gastric myofibroblasts slows tumor growth and is
      decreased with cancer progression.
AB  - Tumor progression has been linked to changes in the stromal environment.
      Myofibroblasts are stromal cells that are often increased in tumors but their
      contribution to cancer progression is not well understood. Here, we show that the
      secretomes of myofibroblasts derived from gastric cancers [cancer-associated
      myofibroblasts (CAMs)] differ in a functionally significant manner from those
      derived from adjacent tissue [adjacent tissue myofibroblasts (ATMs)]. CAMs showed
      increased rates of migration and proliferation compared with ATMs or normal
      tissue myofibroblasts (NTMs). Moreover, conditioned medium (CM) from CAMs
      significantly stimulated migration, invasion and proliferation of gastric cancer
      cells compared with CM from ATMs or NTMs. Proteomic analysis of myofibroblast
      secretomes revealed decreased abundance of the extracellular matrix (ECM) adaptor
      protein like transforming growth factor-beta-induced gene-h3 (TGFbetaig-h3) in
      CAMs, which was correlated with lymph node involvement and shorter survival.
      TGFbetaig-h3 inhibited IGF-II-stimulated migration and proliferation of both
      cancer cells and myofibroblasts, and suppressed IGF-II activation of p42/44
      MAPkinase; TGFbetaig-h3 knockdown increased IGF-II- and CM-stimulated migration.
      Furthermore, administration of TGFbetaig-h3 inhibited myofibroblast-stimulated
      growth of gastric cancer xenografts. We conclude that stromal cells exert
      inhibitory as well as stimulatory effects on tumor cells; TGFbetaig-h3 is a
      stromal inhibitory factor that is decreased with progression of gastric cancers.

PMID- 22610074
TI  - Epigenetic alteration of CCDC67 and its tumor suppressor function in gastric
      cancer.
AB  - In this study, the promoter of the gene coiled-coil domain-containing 67 (CCDC67)
      was found to be frequently methylated in gastric cancer cell lines and in primary
      gastric tumors, as examined by restriction landmark genomic scanning. In
      addition, CCDC67 expression was down-regulated in 72.7% of gastric cancer cell
      lines tested. In most cases, gene down-regulation was associated with CpG
      hypermethylation in the CCDC67 promoter. Treatment with 5-aza-2'-deoxycytidine
      and/or trichostatin A restored CCDC67 expression in down-regulated cell lines.
      Pyrosequencing analysis of 150 paired primary gastric cancer samples revealed
      that promoter CpG methylation was increased in 74% of tested tumors compared with
      paired adjacent normal tissues, and this hypermethylation correlated
      significantly with down-regulation of CCDC67. CCDC67 protein was localized to the
      cell membrane by immunocytochemistry. Stable transfection of a CCDC67 gene in one
      gastric cancer cell line inhibited adhesion-dependent and -independent colony
      formation, and CCDC67 expression suppressed tumorigenesis in nude mice. We
      suggest that CCDC67 is a putative tumor suppressor gene that is silenced in
      gastric cancers by promoter CpG methylation and that it may play an important
      role in cell signaling and migration related to tumorigenesis.

PMID- 22610073
TI  - As an independent unfavorable prognostic factor, IL-8 promotes metastasis of
      nasopharyngeal carcinoma through induction of epithelial-mesenchymal transition
      and activation of AKT signaling.
AB  - Nasopharyngeal carcinoma (NPC) has the highest metastatic potential among head
      and neck cancers. Distant metastasis is the major cause of treatment failure. The
      role of interleukin-8 (IL-8) in NPC progression remains unknown. Our multivariate
      survival analyses of 255 patients with NPC revealed that higher IL-8 expression
      in primary NPC tissue was an independent prognostic factor for overall survival,
      disease-free survival, and distant metastasis-free survival of the patients. In
      vitro study revealed that IL-8 was highly expressed in the established high
      metastasis NPC clone S18 relative to the low-metastasis cells. Suppression of IL
      8 by short-hairpin RNA reduced the expression of IL-8 in S18 cells and
      subsequently inhibited migration, invasion, and hepatic metastasis of the cells
      without influencing cellular growth. Overexpression of IL-8 in S26 cells resulted
      in increased migration, invasion, and metastasis capabilities of the cells
      without affecting cellular growth. Exogenous IL-8 enhanced the migration and
      invasion of low-metastasis CNE-2 cells in a dose-dependent manner. An epithelial
      mesenchymal transition (EMT) could be induced by IL-8 in various NPC cell lines.
      The high level of phosphorylated AKT in S18 cells could be suppressed by knocking
      down IL-8 expression. Further, IL-8-promoted migration and invasion could be
      abolished by either the application of the phosphoinositide-3-kinase inhibitor
      LY294002 or the knock down of AKT expression by using small-interfering RNA. In
      summary, IL-8 serves as an independent prognostic indicator of overall survival,
      disease-free survival, and metastasis-free survival for patients with NPC. IL-8
      promotes NPC metastasis via autocrine and paracrine means, involving activation
      of AKT signaling and inducing EMT in NPC cells.

PMID- 22610075
TI  - Single-CpG-resolution methylome analysis identifies clinicopathologically
      aggressive CpG island methylator phenotype clear cell renal cell carcinomas.
AB  - To clarify the significance of DNA methylation alterations during renal
      carcinogenesis, methylome analysis using single-CpG-resolution Infinium array was
      performed on 29 normal renal cortex tissue (C) samples, 107 non-cancerous renal
      cortex tissue (N) samples obtained from patients with clear cell renal cell
      carcinomas (RCCs) and 109 tumorous tissue (T) samples. DNA methylation levels at
      4830 CpG sites were already altered in N samples compared with C samples.
      Unsupervised hierarchical clustering analysis based on DNA methylation levels at
      the 801 CpG sites, where DNA methylation alterations had occurred in N samples
      and were inherited by and strengthened in T samples, clustered clear cell RCCs
      into Cluster A (n = 90) and Cluster B (n = 14). Clinicopathologically aggressive
      tumors were accumulated in Cluster B, and the cancer-free and overall survival
      rates of patients in this cluster were significantly lower than those of patients
      in Cluster A. Clear cell RCCs in Cluster B were characterized by accumulation of
      DNA hypermethylation on CpG islands and considered to be CpG island methylator
      phenotype (CIMP)-positive cancers. DNA hypermethylation of the CpG sites on the
      FAM150A, GRM6, ZNF540, ZFP42, ZNF154, RIMS4, PCDHAC1, KHDRBS2, ASCL2, KCNQ1,
      PRAC, WNT3A, TRH, FAM78A, ZNF671, SLC13A5 and NKX6-2 genes became hallmarks of
      CIMP in RCCs. On the other hand, Cluster A was characterized by genome-wide DNA
      hypomethylation. These data indicated that DNA methylation alterations at
      precancerous stages may determine tumor aggressiveness and patient outcome.
      Accumulation of DNA hypermethylation on CpG islands and genome-wide DNA
      hypomethylation may each underlie distinct pathways of renal carcinogenesis.

PMID- 22610076
TI  - miR-181a/b significantly enhances drug sensitivity in chronic lymphocytic
      leukemia cells via targeting multiple anti-apoptosis genes.
AB  - MicroRNAs (miRNAs) have been shown to play critical roles in regulating the
      progress of leukemia. We performed miRNA expression profile in six Chinese
      patients with chronic lymphocytic leukemia (CLL), and in peripheral B cells from
      pooled 30 healthy donors, using a platform containing 866 human miRNAs. The most
      frequent changes in miRNAs in CLL cells included downregulation of miR-126, miR
      572, miR-494, miR-923, miR-638, miR-130a, miR-181a and miR-181b and up-regulation
      of miR-29a, miR-660, miR-20a, miR-106b, miR-142-5p, miR-101, miR-30b, miR-34a,
      miR-let-7f, miR-21 and miR-155. Among the miRNAs down-regulated in CLL cells, we
      showed that miR-181a/b expression levels were significantly lower in poor
      prognostic subgroups defined by unmutated immunoglobulin heavy chain variable
      status and p53 aberrations. Furthermore, under-expression of miR-181a and miR
      181b was associated with shorter overall survival and treatment-free survival in
      CLL patients. We further evaluated fludarabine-induced apoptosis after
      transfection of primary CLL cells from 40 patients with miR-15a, miR-16-1, miR
      34a, miR-181a and miR-181b mimics. Transfection of miR-34a, miR-181a and miR-181b
      mimics into CLL cells from p53 wild-type patients led to significant increase in
      apoptosis compared with miRNA control. However, enforced expression of these
      miRNAs had no effect on B-CLL cells from p53-attenuated patients. We further
      demonstrated that miR-181a and miR-181b inhibiting BCL-2, MCL-1 and X-linked
      inhibitor of apoptosis protein by direct binding to 3'UTR. Thus, these results
      suggest that miR-181a/b may play important roles in the pathogenesis of CLL and
      may provide a possible therapeutic avenue and a sensitive indicator of the
      activity of the p53 axis in CLL.

PMID- 22610078
TI  - Case of fake acute abdomen by metastatic melanoma.
AB  - Malignant melanoma is the neoplasm with highest probability of cardiac
      metastatization. Cardiac involvement by metastatic melanoma is rarely identified
      ante-mortem (5-30% of cases) for non-specificity of cardiac symptoms. In fact we
      show in this case report that abdominal pain can represent the predominant
      symptom. Furthermore we show the importance of linkage between clinical &
      anamnestic data which if underestimated can lead to an improper management and to
      the patient exitus.

PMID- 22610079
TI  - Factors predicting in-hospital mortality of patients with diffuse peritonitis
      from perforated colonic diverticulitis.
AB  - AIM: Diverticulitis free perforation still remains a major life-threatening
      condition. Herein we evaluate factors influencing prognosis of patients with
      perforated colonic diverticulitis and the current validity of Mannheim
      Peritonitis Index (MPI) in predicting mortality. MATERIAL OF STUDY: From January
      2000 to October 2010, 39 patients were operated on for generalized peritonitis
      from perforated diverticulitis RESULTS: Five postoperative deaths (12.8%) related
      to septic shock occurred. A cross-sectional study between deceased and non
      deceased patients was carried out. Deceased patients were significantly older
      than non-deceased (76.4 vs. 59.1 years,p=0.019); duration of symptoms was longer
      in deceased patients (102 vs. 26.9 hours, p=0.000); MPI was higher in deceased
      patients (31.4 vs. 21.2, p=0.000). Age, duration of symptoms and MPI were
      independent risk factors predicting poor prognosis. The highest sensitivity and
      specificity of MPI in predicting mortality was shown for a score higher than 27.
      CONCLUSIONS: MPI is still effective in predicting postoperative mortality. People
      who nurse older persons must pay higher attention to complaints in order to
      reduce the delay in hospitalization.

PMID- 22610080
TI  - Intestinal occlusion caused by endometriosis of the sigmoid colon.
AB  - Endometriosis (E) is an estrogen-dependent inflammatory disorder that is observed
      in approximately 10% of women in childbearing age, and is the most common benign
      gynecological disorder requiring hospitalization. In 5% of cases, there is an
      involvement of the gastrointestinal tract, for the most part of the sigmoid colon
      and rectum (~ 90%). However intestinal obstruction due to severe stenosis of the
      sigmoid colon, as in the case described by the authors, is rare. The differential
      diagnosis should include cancer, inflammatory diseases and actinic colitis which
      has a similar clinical picture to E. Surgical treatment - resection and
      anastomosis or conservative procedures - provides better results especially when
      a multidisciplinary approach is used (colorectal surgeon, gynecologist,
      urologist). The authors report a case of obstruction of the sigmoid colon due to
      endometriosis and analyze the pathophysiology, diagnosis and surgical management
      of this disorder.

PMID- 22610081
TI  - Cystosarcoma phyllodes with muscular and lymph node metastasis. Our experience
      and review of the literature.
AB  - BACKGROUND: Phyllodes tumors are biphasic fibroepithelial neoplasms of the
      breast. While the surgical management of these relatively uncommon tumors has
      been addressed in the literature, few reports have commented on the surgical
      approach to tumors greater than ten centimeters in diameter - the giant phyllodes
      tumor. CASE REPORT: We report a case of a 45-year-old woman who presented with a
      large lump in her right breast, involvement of multiple ipsilateral axillary
      lymph nodes and pectoralis major muscle. Clinical findings and cytologic
      examination (fine-needle aspiration) were suggestive of cystosarcoma phyllodes
      and we discuss the techniques utilized for pre-operative diagnosis, tumor
      removal, and breast reconstruction. A review of the literature on the surgical
      management of phyllodes tumors was performed. CONCLUSION: Management of the
      phyllodes tumor presents the surgeon with unique challenges. The majority of
      these tumors can be managed by simple mastectomy. In our case clinical findings
      and cytologic examination (fine-needle aspiration) were suggestive of
      cystosarcoma phyllodes, for which the patient underwent a modified radical
      mastectomy. Postoperative radio therapy was given to the loco regional area.
      KEYWORDS: Immediate reconstruction, Phylloides tumors, Post-operative radio
      therapy, Radical surgery.

PMID- 22610082
TI  - The physiologic climate of Nigeria.
AB  - This study describes the spatial and temporal variations in the physiologic
      climate of Nigeria for 1951-2009 in terms of effective temperature (ET),
      temperature-humidity index (THI), relative strain index (RSI) and perception of
      3,600 sampled populations. The main hypotheses are that (i) the existing
      vegetation-based ecological region could adequately elucidate the physiologic
      climate of the country, and (ii) physiologic stress has significantly increased
      over the years (1951-2009). Trends and changes in the selected indices (ET, THI
      and RSI) were examined over two time slices: 1951-1980 and 1981-2009. The results
      show that (1) the montane region was the most comfortable physiologic climate in
      Nigeria, and the regions around the Rivers Niger and Benue troughs were the most
      uncomfortable in most parts of the year, (2) physiologic stress in most parts of
      Nigeria has significantly increased in 1981-2009 over 1951-1980 (p <= 0.05), (3)
      coping strategies to the uncomfortably hot and cold climate in Nigeria are
      limited to dressing mode, clothing materials and use of air conditioners or fan,
      (4) ET, THI and RSI results could be similar, and complementary; but each is with
      its strengths and weaknesses for annual or seasonal representations, which the
      others complemented for the interpretation of the physiologic climate of Nigeria.
      The study concluded that the relationship between the ecological classification
      of Nigeria and physiologic climate is rather complex, and the former could not
      elucidate the latter. The study cited inadequate meteorological data, especially
      on wind chill, and health records as limiting factors of studies on the Nigerian
      physiologic climates and the effect of extreme thermal conditions on the people.

PMID- 22610084
TI  - Ubiquitin-based anticancer therapy: carpet bombing with proteasome inhibitors vs
      surgical strikes with E1, E2, E3, or DUB inhibitors.
AB  - The proteasome inhibitor bortezomib remains the only ubiquitin pathway effector
      to become a drug (VELCADE(r)) and has become a successful treatment for
      hematological malignancies. While producing a global cellular effect, proteasome
      inhibitors have not triggered the catastrophe articulated initially in terms such
      as "buildup of cellular garbage". Proteasome inhibitors, in fact, do have a
      therapeutic window, although in the case of the prototype bortezomib it is small
      owing to peripheral neuropathy, myelosuppression and, as recently reported,
      cardiotoxicity [1]. Currently, several second-generation molecules are undergoing
      clinical evaluation to increase this window. An alternative strategy is to target
      ubiquitin pathway enzymes acting at non-proteasomal sites-E1, E2, and E3,
      associated with ubiquitin conjugation, and deubiquitylating enzymes ("DUBs")-that
      act locally on selected targets rather than on the whole cell. Inhibitors (or
      activators, in some cases) of these enzymes should be developable as selective
      antitumor agents with toxicity profiles superior to that of bortezomib. Various
      therapeutic hypotheses follow from known cellular mechanisms of these target
      enzymes; most hypotheses relate to cancer, reminiscent of the FDA-approved
      protein kinase inhibitors now marketed. Since ubiquitin tagging controls the
      cellular content, activity, or compartmentation of proteins associated with
      disease, inhibitors or activators of ubiquitin conjugation or deconjugation are
      predicted to have an impact on disease. For practical and empirical reasons,
      inhibitors of ubiquitin pathway enzymes have been the favored therapeutic avenue.
      In approximately the time that has elapsed since the approval of bortezomib in
      2003, there has been some progress in developing potential anticancer drugs that
      target various ubiquitin pathway enzymes. An E1 inhibitor and inhibitors of E3
      are now in clinical trial, with some objective responses reported. Appropriate
      assays and/or rational design may uncover improved inhibitors of these enzymes,
      as well as E2 and DUBs, for further development. Presently, it should become
      clear whether one or both of the two general strategies for ubiquitin-based drug
      discovery will lead to truly superior new medicines for cancer and other
      diseases. This article is part of a Special Issue entitled: Ubiquitin Drug
      Discovery and Diagnostics.

PMID- 22610085
TI  - Genetic polymorphisms in the ITPKC gene and cervical squamous cell carcinoma
      risk.
AB  - Cervical cancer is caused primarily by infection with oncogenic types of human
      papillomavirus (HPV). However, HPV infection alone is not sufficient for the
      progression to cervical cancer. Host immunogenetic factors may involve in the
      development of this disease. Inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) is
      recently shown to act as a negative regulator of T-cell activation. We aim to
      study if polymorphisms in the ITPKC gene are associated with the risk of cervical
      cancer in Taiwanese women. ITPKC rs28493229 C/G, rs890934 G/T, rs2303723 C/T, and
      rs10420685 A/G polymorphisms were genotyped in a hospital-based study of 465
      women with cervical squamous cell carcinoma (CSCC) and 800 age-matched healthy
      control women. The presence and genotypes of HPV in CSCC were determined. The
      frequency of G/G genotype and G allele of the ITPKC rs28493229 polymorphism was
      significantly higher in patients with CSCC compared with controls (OR = 1.81, 95
      % CI 1.20-2.73, P = 0.005, P (c) = 0.02; OR = 1.70, 95 % CI 1.14-2.54, P = 0.008,
      P (c) = 0.03, respectively). No significant associations were found for other 3
      polymorphisms. Haplotype analysis revealed the distribution of haplotype CGTA was
      significantly reduced in women with CSCC (OR = 0.59, 95 % CI 0.40-0.89, P = 0.01,
      P (c) = 0.04). In conclusion, we found the G/G genotype and G allele of the ITPKC
      rs28493229 polymorphism may contribute to the risk of CSCC in Taiwanese women.
      This finding provides new insights into the mechanisms of immune activation in
      cervical cancer.

PMID- 22610086
TI  - A crucial role for basic emotion awareness in the development of emotion
      regulation?

PMID- 22610088
TI  - High-throughput identification of informative nuclear loci for shallow-scale
      phylogenetics and phylogeography.
AB  - One of the major challenges for researchers studying phylogeography and shallow
      scale phylogenetics is the identification of highly variable and informative
      nuclear loci for the question of interest. Previous approaches to locus
      identification have generally required extensive testing of anonymous nuclear
      loci developed from genomic libraries of the target taxon, testing of loci of
      unknown utility from other systems, or identification of loci from the nearest
      model organism with genomic resources. Here, we present a fast and economical
      approach to generating thousands of variable, single-copy nuclear loci for any
      system using next-generation sequencing. We performed Illumina paired-end
      sequencing of three reduced-representation libraries (RRLs) in chorus frogs
      (Pseudacris) to identify orthologous, single-copy loci across libraries and to
      estimate sequence divergence at multiple taxonomic levels. We also conducted PCR
      testing of these loci across the genus Pseudacris and outgroups to determine
      whether loci developed for phylogeography can be extended to deeper phylogenetic
      levels. Prior to sequencing, we conducted in silico digestion of the most closely
      related reference genome (Xenopus tropicalis) to generate expectations for the
      number of loci and degree of coverage for a particular experimental design. Using
      the RRL approach, we: (i) identified more than 100,000 single-copy nuclear loci,
      6339 of which were obtained for divergent conspecifics and 904 of which were
      obtained for heterospecifics; (ii) estimated average nuclear sequence divergence
      at 0.1% between alleles within an individual, 1.1% between conspecific
      individuals that represent two different clades, and 1.8% between species; and
      (iii) determined from PCR testing that 53% of the loci successfully amplify
      within-species and also many amplify to the genus-level and deeper in the
      phylogeny (16%). Our study effectively identified nuclear loci present in the
      genome that have levels of sequence divergence on par with mitochondrial loci
      commonly used in phylogeography. Specifically, we estimated that ~7% of loci in
      the chorus frog genome are >3% divergent within species; this translates to a
      prediction of approximately 50,000 single-copy loci in the genome with >3%
      divergence. Moreover, successful amplification of many loci at deeper
      phylogenetic levels indicates that the RRL approach represents an efficient
      method for rapid identification of informative loci for both phylogenetics and
      phylogeography. We conclude by making recommendations for minimizing the cost and
      maximizing the efficiency of locus identification for future studies in this
      field.

PMID- 22610083
TI  - Mammalian iron metabolism and its control by iron regulatory proteins.
AB  - Cellular iron homeostasis is maintained by iron regulatory proteins 1 and 2 (IRP1
      and IRP2). IRPs bind to iron-responsive elements (IREs) located in the
      untranslated regions of mRNAs encoding protein involved in iron uptake, storage,
      utilization and export. Over the past decade, significant progress has been made
      in understanding how IRPs are regulated by iron-dependent and iron-independent
      mechanisms and the pathological consequences of IRP2 deficiency in mice. The
      identification of novel IREs involved in diverse cellular pathways has revealed
      that the IRP-IRE network extends to processes other than iron homeostasis. A
      mechanistic understanding of IRP regulation will likely yield important insights
      into the basis of disorders of iron metabolism. This article is part of a Special
      Issue entitled: Cell Biology of Metals.

PMID- 22610090
TI  - Design, synthesis and binding studies of a novel quadruple ADDA hydrogen-bond
      array.
AB  - The design and synthesis of a novel ADDA hydrogen-bond array is described. The
      ureidodiimidazole motif (UDIM) 2 engages in interactions with complementary
      diamidonaphthyridine (DAN) 3 motifs with an association constant K(a) = 825 +/-
      16 M(-1) in chloroform. (1)H NMR and molecular modelling studies were carried out
      in order to explain the unexpected behaviour of this new supramolecular motif.
      These revealed that a combination of effects including; an energetic bias for the
      folded conformer, subtle differences in shape complementarity between the two
      components and the potential for self-association of UDIM 2 disfavour higher
      affinity interactions between the two components.

PMID- 22610091
TI  - Clinical experience with low-dose continuous infusion of furosemide in acute
      heart failure: assessment of efficacy and safety.
AB  - INTRODUCTION: Clinical data are scarce for furosemide administered as a low-dose
      (<160 mg/24 hours) continuous intravenous infusion in acute heart failure (HF).
      Our purpose was to evaluate the efficacy and safety of low-dose continuous
      infusion of furosemide on diuretic response, renal function, and patient
      outcomes. METHODS: A retrospective study of patients with acute HF who received
      furosemide administered as a continuous infusion after initial therapy with
      intermittent boluses (usually 40-80 mg every 12 hours). End points included mean
      hourly urine output, incidence of acute renal injury, and outcome disparities of
      patients who developed acute renal injury. Comparison of patients with preserved
      and reduced left ventricular ejection fraction (LVEF) was also performed.
      RESULTS: The study included 150 patients (age 57 +/- 13 years, male gender 61%,
      admission weight 87 +/- 32 kg, LVEF 37 +/- 15%, 28% preserved LVEF). Mean initial
      and maximum furosemide doses were 5.1 +/- 1.1 mg/h and 6.2 +/- 2.2 mg/h,
      respectively. Mean duration of therapy was 51.4 +/- 67.5 hours. Continuous
      infusion of furosemide was associated with a significant increase in mean hourly
      urine output compared to baseline (150 +/- 77 mL/h vs 116 +/- 69 mL/h, P < .001).
      Acute renal injury developed in 19% of patients, with 70% of those occurring
      within the first 48 hours of therapy. Mean serum creatinine (baseline 1.55 +/-
      1.50 mg/dL vs at discharge 1.64 +/- 1.61 mg/dL, P = .20) and estimated glomerular
      filtration rate (baseline 67 +/- 39 mL/min vs at discharge 67 +/- 43 mL/min, P =
      .89) did not significantly change over the course of the hospitalization.
      Development of acute renal injury was associated with poorer outcomes, higher
      furosemide dose, and longer duration of furosemide therapy. Diuretic response and
      safety were not different between patients with preserved or reduced LVEF.
      CONCLUSIONS: In patients with acute HF, furosemide administered as a low-dose
      continuous infusion was effective in achieving diuresis and was not associated
      with a detectable effect on renal function. This diuretic approach appeared to be
      similarly effective and safe in patients with preserved LVEF.

PMID- 22610092
TI  - Respiratory health status of US Army personnel potentially exposed to smoke from
      2003 Al-Mishraq Sulfur Plant fire.
AB  - OBJECTIVE: To assess the impact of exposure to a 2003 sulfur plant fire on the
      health of deployed US Army personnel. METHODS: The authors identified a small
      firefighter group known to be at the fire source and a larger, more dispersed
      population. Self-reported health status and respiratory health outcomes for these
      two groups were reviewed compared with two unexposed groups. RESULTS: Self
      reported health concerns, difficulty breathing, and shortness of breath were
      common in the exposed. Rates for chronic respiratory conditions increased in all
      groups from before to after deployment. Postdeployment medical encounters for
      chronic respiratory conditions among the exposed did not differ significantly
      from the unexposed comparison groups. CONCLUSION: Potential exposure to the
      sulfur fire was positively associated with self-reported health concerns and
      symptoms but not with clinical encounters for chronic respiratory health
      conditions.

PMID- 22610093
TI  - The membrane lipid phosphatidylcholine is an unexpected source of triacylglycerol
      in the liver.
AB  - The increased prevalence of obesity and diabetes in human populations can induce
      the deposition of fat (triacylglycerol) in the liver (steatosis). The current
      view is that most hepatic triacylglycerols are derived from fatty acids released
      from adipose tissue. In this study, we show that phosphatidylcholine (PC), an
      important structural component of cell membranes and plasma lipoproteins, can be
      a precursor of ~65% of the triacylglycerols in liver. Mice were injected with
      [(3)H]PC-labeled high density lipoproteins (HDLs). Hepatic uptake of HDL-PC was
      ~10 MUmol/day, similar to the rate of hepatic de novo PC synthesis. Consistent
      with this finding, measurement of the specific radioactivity of PC in plasma and
      liver indicated that 50% of hepatic PC is derived from the circulation. Moreover,
      one-third of HDL-derived PC was converted into triacylglycerols. Importantly,
      ~65% of the total hepatic pool of triacylglycerol appears to be derived from
      hepatic PC, half of which is derived from HDL. Thus, lipoprotein-associated PC
      should be considered a quantitatively significant source of triacylglycerol for
      the etiology of hepatic steatosis.

PMID- 22610094
TI  - Annexin A1 interaction with the FPR2/ALX receptor: identification of distinct
      domains and downstream associated signaling.
AB  - Understanding how proresolving agonists selectively activate FPR2/ALX is a
      crucial step in the clarification of proresolution molecular networks that can be
      harnessed for the design of novel therapeutics for inflammatory disease.
      FPR2/ALX, a G protein-coupled receptor belonging to the formyl peptide receptor
      (FPR) family, conveys the biological functions of a variety of ligands, including
      the proresolution mediators annexin A1 (AnxA1) and lipoxin A(4), as well as the
      activating and proinflammatory protein serum amyloid A. FPR2/ALX is the focus of
      intense screening for novel anti-inflammatory therapeutics, and the small
      molecule compound 43 was identified as a receptor ligand. Here, we used chimeric
      FPR1 and FPR2/ALX clones (stably transfected in HEK293 cells) to identify the N
      terminal region and extracellular loop II as the FPR2/ALX domain required for
      AnxA1-mediated signaling. Genomic responses were also assessed with domain
      specific effects emerging, so the N-terminal region is required for AnxA1
      induction of JAG1 and JAM3, whereas it is dispensable for modulation of SGPP2. By
      comparison, serum amyloid A non-genomic responses were reliant on extracellular
      loops I and II, whereas the small molecule compound 43 activated extracellular
      loop I with downstream signaling dependent on transmembrane region II. In
      desensitization experiments, the N-terminal region was dispensable for AnxA1
      induced FPR2/ALX down-regulation in both the homologous and heterologous
      desensitization modes.

PMID- 22610095
TI  - Engineering an improved IgG4 molecule with reduced disulfide bond heterogeneity
      and increased Fab domain thermal stability.
AB  - The integrity of antibody structure, stability, and biophysical characterization
      are becoming increasingly important as antibodies receive increasing scrutiny
      from regulatory authorities. We altered the disulfide bond arrangement of an IgG4
      molecule by mutation of the Cys at the N terminus of the heavy chain constant
      domain 1 (C(H)1) (Kabat position 127) to a Ser and introduction of a Cys at a
      variety of positions (positions 227-230) at the C terminus of C(H)1. An inter-LC
      C(H)1 disulfide bond is thus formed, which mimics the disulfide bond arrangement
      found in an IgG1 molecule. The antibody species present in the supernatant
      following transient expression in Chinese hamster ovary cells were analyzed by
      immunoblot to investigate product homogeneity, and purified product was analyzed
      by a thermofluor assay to determine thermal stability. We show that the light
      chain can form an inter-LC-C(H)1 disulfide bond with a Cys when present at
      several positions on the upper hinge (positions 227-230) and that such engineered
      disulfide bonds can consequently increase the Fab domain thermal stability
      between 3 and 6.8  degrees C. The IgG4 disulfide mutants displaying the greatest
      increase in Fab thermal stability were also the most homogeneous in terms of
      disulfide bond arrangement and antibody species present. Importantly, mutations
      did not affect the affinity for antigen of the resultant molecules. In
      combination with the previously described S241P mutation, we present an IgG4
      molecule with increased Fab thermal stability and reduced product heterogeneity
      that potentially offers advantages for the production of IgG4 molecules.

PMID- 22610096
TI  - Raf kinase inhibitor protein (RKIP) dimer formation controls its target switch
      from Raf1 to G protein-coupled receptor kinase (GRK) 2.
AB  - Proteins controlling cellular networks have evolved distinct mechanisms to ensure
      specificity in protein-protein interactions. Raf kinase inhibitor protein (RKIP)
      is a multifaceted kinase modulator, but it is not well understood how this small
      protein (21 kDa) can coordinate its diverse signaling functions. Raf1 and G
      protein-coupled receptor kinase (GRK) 2 are direct interaction partners of RKIP
      and thus provide the possibility to untangle the mechanism of its target
      specificity. Here, we identify RKIP dimer formation as an important mechanistic
      feature in the target switch from Raf1 to GRK2. Co-immunoprecipitation and cross
      linking experiments revealed RKIP dimerization upon phosphorylation of RKIP at
      serine 153 utilizing purified proteins as well as in cells overexpressing RKIP. A
      functional phosphomimetic RKIP mutant had a high propensity for dimerization and
      reproduced the switch from Raf1 to GRK2. RKIP dimerization and GRK2 binding, but
      not Raf1 interaction, were prevented by a peptide comprising amino acids 127-146
      of RKIP, which suggests that this region is critical for dimer formation.
      Furthermore, a dimeric RKIP mutant displayed a higher affinity to GRK2, but a
      lower affinity to Raf1. Functional analyses of phosphomimetic as well as dimeric
      RKIP demonstrated that enhanced dimerization of RKIP translates into decreased
      Raf1 and increased GRK2 inhibition. The detection of RKIP dimers in a complex
      with GRK2 in murine hearts implies their physiological relevance. These findings
      represent a novel mechanistic feature how RKIP can discriminate between its
      different interaction partners and thus advances our understanding how specific
      inhibition of kinases can be achieved.

PMID- 22610097
TI  - Coiled coil domain-containing protein 56 (CCDC56) is a novel mitochondrial
      protein essential for cytochrome c oxidase function.
AB  - In Drosophila melanogaster, the mitochondrial transcription factor B1 (d-mtTFB1)
      transcript contains in its 5'-untranslated region a conserved upstream open
      reading frame denoted as CG42630 in FlyBase. We demonstrate that CG42630 encodes
      a novel protein, the coiled coil domain-containing protein 56 (CCDC56), conserved
      in metazoans. We show that Drosophila CCDC56 protein localizes to mitochondria
      and contains 87 amino acids in flies and 106 in humans with the two proteins
      sharing 42% amino acid identity. We show by rapid amplification of cDNA ends and
      Northern blotting that Drosophila CCDC56 protein and mtTFB1 are encoded on a bona
      fide bicistronic transcript. We report the generation and characterization of two
      ccdc56 knock-out lines in Drosophila carrying the ccdc56(D6) and ccdc56(D11)
      alleles. Lack of the CCDC56 protein in flies induces a developmental delay and
      100% lethality by arrest of larval development at the third instar. ccdc56 knock
      out larvae show a significant decrease in the level of fully assembled cytochrome
      c oxidase (COX) and in its activity, suggesting a defect in complex assembly; the
      activity of the other oxidative phosphorylation complexes remained either
      unaffected or increased in the ccdc56 knock-out larvae. The lethal phenotype and
      the decrease in COX were partially rescued by reintroduction of a wild-type UAS
      ccdc56 transgene. These results indicate an important role for CCDC56 in the
      oxidative phosphorylation system and in particular in COX function required for
      proper development in D. melanogaster. We propose CCDC56 as a candidate factor
      required for COX biogenesis/assembly.

PMID- 22610098
TI  - Endoproteolytic cleavage of TUG protein regulates GLUT4 glucose transporter
      translocation.
AB  - To promote glucose uptake into fat and muscle cells, insulin causes the
      translocation of GLUT4 glucose transporters from intracellular vesicles to the
      cell surface. Previous data support a model in which TUG traps GLUT4-containing
      vesicles and tethers them intracellularly in unstimulated cells and in which
      insulin mobilizes this pool of vesicles by releasing this tether. Here we show
      that TUG undergoes site-specific endoproteolytic cleavage, which separates a
      GLUT4-binding, N-terminal region of TUG from a C-terminal region previously
      suggested to bind an intracellular anchor. Cleavage is accelerated by insulin
      stimulation in 3T3-L1 adipocytes and is highly dependent upon adipocyte
      differentiation. The N-terminal TUG cleavage product has properties of a novel 18
      kDa ubiquitin-like modifier, which we call TUGUL. The C-terminal product is
      observed at the expected size of 42 kDa and also as a 54-kDa form that is
      released from membranes into the cytosol. In transfected cells, intact TUG links
      GLUT4 to PIST and also binds Golgin-160 through its C-terminal region. PIST is an
      effector of TC10alpha, a GTPase previously shown to transmit an insulin signal
      required for GLUT4 translocation, and we show using RNAi that TC10alpha is
      required for TUG proteolytic processing. Finally, we demonstrate that a cleavage
      resistant form of TUG does not support highly insulin-responsive GLUT4
      translocation or glucose uptake in 3T3-L1 adipocytes. Together with previous
      results, these data support a model whereby insulin stimulates TUG cleavage to
      liberate GLUT4 storage vesicles from the Golgi matrix, which promotes GLUT4
      translocation to the cell surface and enhances glucose uptake.

PMID- 22610099
TI  - Phosphodiesterase 4B mediates extracellular signal-regulated kinase-dependent up
      regulation of mucin MUC5AC protein by Streptococcus pneumoniae by inhibiting cAMP
      protein kinase A-dependent MKP-1 phosphatase pathway.
AB  - Otitis media (OM) is the most common childhood bacterial infection and the major
      cause of conductive hearing loss in children. Mucus overproduction is a hallmark
      of OM. Streptococcus pneumoniae is the most common gram-positive bacterial
      pathogen causing OM. Among many mucin genes, MUC5AC has been found to be greatly
      up-regulated in the middle ear mucosa of human patients with OM. We previously
      reported that S. pneumoniae up-regulates MUC5AC expression in a MAPK ERK
      dependent manner. We also found that MAPK phosphatase-1 (MKP-1) negatively
      regulates S. pneumoniae-induced ERK-dependent MUC5AC up-regulation. Therapeutic
      strategies for up-regulating the expression of negative regulators such as MKP-1
      may have significant therapeutic potential for treating mucus overproduction in
      OM. However, the underlying molecular mechanism by which MKP-1 expression is
      negatively regulated during S. pneumoniae infection is unknown. In this study we
      show that phosphodiesterase 4B (PDE4B) mediates S. pneumoniae-induced MUC5AC up
      regulation by inhibiting the expression of a negative regulator MKP-1, which in
      turn leads to enhanced MAPK ERK activation and subsequent up-regulation of
      MUC5AC. PDE4B inhibits MKP-1 expression in a cAMP-PKA-dependent manner. PDE4
      specific inhibitor rolipram inhibits S. pneumoniae-induced MUC5AC up-regulation
      both in vitro and in vivo. Moreover, we show that PDE4B plays a critical role in
      MUC5AC induction. Finally, topical and post-infection administration of rolipram
      into the middle ear potently inhibited S. pneumoniae-induced MUC5AC up
      regulation. Collectively, these data demonstrate that PDE4B mediates ERK
      dependent up-regulation of mucin MUC5AC by S. pneumoniae by inhibiting cAMP-PKA
      dependent MKP-1 pathway. This study may lead to novel therapeutic strategy for
      inhibiting mucus overproduction.

PMID- 22610100
TI  - Cleavage of the NR2B subunit amino terminus of N-methyl-D-aspartate (NMDA)
      receptor by tissue plasminogen activator: identification of the cleavage site and
      characterization of ifenprodil and glycine affinities on truncated NMDA receptor.
AB  - Thrombolysis using tissue plasminogen activator (tPA) has been the key treatment
      for patients with acute ischemic stroke for the past decade. Recent studies,
      however, suggest that this clot-busting protease also plays various roles in
      brain physiological and pathophysiological glutamatergic-dependent processes,
      such as synaptic plasticity and neurodegeneration. In addition, increasing
      evidence implicates tPA as an important neuromodulator of the N-methyl-d
      aspartate (NMDA) receptors. Here, we demonstrate that recombinant human tPA
      cleaves the NR2B subunit of NMDA receptor. Analysis of NR2B in rat brain lysates
      and cortical neurons treated with tPA revealed concentration- and time-dependent
      degradation of NR2B proteins. Peptide sequencing studies performed on the cleaved
      off products obtained from the tPA treatment on a recombinant fusion protein of
      the amino-terminal domain of NR2B revealed that tPA-mediated cleavage occurred at
      arginine 67 (Arg(67)). This cleavage is tPA-specific, plasmin-independent, and
      removes a predicted ~4-kDa fragment (Arg(27)-Arg(67)) from the amino-terminal
      domain of the NR2B protein. Site-directed mutagenesis of putative cleavage site
      Arg(67) to Ala(67) impeded tPA-mediated degradation of recombinant protein. This
      analysis revealed that NR2B is a novel substrate of tPA and suggested that an
      Arg(27)-Arg(67)-truncated NR2B-containing NMDA receptor could be formed.
      Heterologous expression of NR2B with Gln(29)-Arg(67) deleted is functional but
      exhibits reduced ifenprodil inhibition and increased glycine EC(50) with no
      change in glutamate EC(50). Our results confirmed NR2B as a novel proteolytic
      substrate of tPA, where tPA may directly interact with NR2B subunits leading to a
      change in pharmacological properties of NR2B-containing NMDA receptors.

PMID- 22610101
TI  - Arrestin scaffolds NHERF1 to the P2Y12 receptor to regulate receptor
      internalization.
AB  - We have recently shown in a patient with mild bleeding that the PDZ-binding motif
      of the platelet G protein-coupled P2Y(12) receptor (P2Y(12)R) is required for
      effective receptor traffic in human platelets. In this study we show for the
      first time that the PDZ motif-binding protein NHERF1 exerts a major role in
      potentiating G protein-coupled receptor (GPCR) internalization. NHERF1 interacts
      with the C-tail of the P2Y(12)R and unlike many other GPCRs, NHERF1 interaction
      is required for effective P2Y(12)R internalization. In vitro and prior to agonist
      stimulation P2Y(12)R/NHERF1 interaction requires the intact PDZ binding motif of
      this receptor. Interestingly on receptor stimulation NHERF1 no longer interacts
      directly with the receptor but instead binds to the receptor via the endocytic
      scaffolding protein arrestin. These findings suggest a novel model by which
      arrestin can serve as an adaptor to promote NHERF1 interaction with a GPCR to
      facilitate effective NHERF1-dependent receptor internalization.

PMID- 22610102
TI  - Biomarkers of teratogenesis: suggestions from animal studies.
AB  - Biomarkers of effect are measurable biochemical, physiological or other
      alterations within an organism that can be recognized as causing an established
      or potential impairment of embryo-fetal development. They may be identified
      studying the mechanisms of action of teratogens. Hyperacetylation of histones,
      oxidative stress, cholesterol and retinoic acid unbalance are some of the
      identified mechanisms of action of some known teratogens. Nevertheless, their use
      is not currently applicable in human pregnancy because of the difficulty of the
      choice of biological material, the time when the material must be obtained, and
      the invasivity of methods. Furthermore, before using them in human pregnancy
      studies, biomarkers should be validated in experimental animals and in
      epidemiologic studies. On the contrary, some biomarkers could be useful in the
      screening of developmental toxicity of chemicals and drugs, comparing molecules
      of the same chemical class or with the similar pharmacologic activity, and using
      adequate in vitro tests, in order to reduce the use of experimental animals.

PMID- 22610103
TI  - Use of a blocking primer allows selective amplification of bacterial DNA from
      microalgae cultures.
AB  - The production of algae is a crucial component of many aquaculture systems and
      the role of bacteria in this process is an important although complex one. We
      report the development of a new blocking primer that allowed PCR amplification of
      bacterial DNA in the presence of algal chloroplast DNA.

PMID- 22610104
TI  - Postherpetic neuralgia: the stealth attacker.

PMID- 22610108
TI  - CMS redesigned Medicare Summary Notices.

PMID- 22610109
TI  - Retrospective analysis of pulsed radiofrequency energy therapy use in the
      treatment of chronic pressure ulcers.
AB  - OBJECTIVE: : The purpose of the study was to evaluate the benefit of using pulsed
      radiofrequency energy (PRFE) therapy in the treatment of chronic pressure ulcers.
      DESIGN: : A retrospective analysis was performed using case series data from the
      Provant Wound Registry, which consists of demographic characteristics and wound
      healing outcomes for patients treated with the Provant Therapy System. SETTING: :
      The analysis subset consisted of data from 39 distinct centers, including both
      residential and ambulatory care facilities. PARTICIPANTS: : The analysis included
      data from 89 patients. The majority of patients (89%) were cared for in
      residential facilities, whereas 11% of patients were cared for in ambulatory care
      facilities. MAIN OUTCOME MEASURES: : Specific outcomes that assessed wound
      healing between the initial time point and at the 4-week follow-up were as
      follows: percent wound surface area reduction (PWAR), proportion of wounds
      achieving 50% reduction or greater in wound surface area (50% PWAR), and the rate
      of wound healing (wound healing trajectory in centimeters squared per day). MAIN
      RESULTS: : Overall, there was a 51% median reduction in wound surface area (PWAR)
      after 4 weeks of PRFE therapy for wounds in the study, with 51% of wounds
      (56/110) achieving 50% reduction or greater in wound surface area (50% PWAR).
      Rate of healing measurements for the overall study group showed a median wound
      healing trajectory of 0.13 cm/d at 4 weeks. CONCLUSION: : Compared with
      historical controls and other studies using similar surrogate wound healing
      markers, these results suggest PRFE therapy is a beneficial adjuvant treatment
      option for healing chronic pressure ulcers.

PMID- 22610110
TI  - Reliability and predictive validity of Inlow's 60-Second Diabetic Foot Screen
      Tool.
AB  - OBJECTIVE: : The purpose of this study was to assess Inlow's 60-Second Diabetic
      Foot Screen Tool to ascertain consistency of risk recognition for development of
      ulceration independent of specific assessor and practice setting. Screening tools
      that assist clinicians in identifying risk require validation. The objectives
      were to determine the intrarater reliability, interrater reliability, and
      predictive validity of Inlow's 60-Second Diabetic Foot Screen Tool in 2
      healthcare settings. DESIGN: : Following ethics board approval, a prospective
      observational study was completed. SETTING AND PARTICIPANTS: : A convenience
      sample of 69 persons with diabetes was recruited: n = 26 from an acute care
      setting (dialysis) and n = 43 from long-term-care (LTC) setting. MAIN OUTCOME
      MEASURES: : The screening tool was administered by 2 assessors independently to
      determine interrater reliability and later the same day by one of the assessors
      to determine intrarater reliability. Occurrence of foot ulcers or amputation was
      noted 1 to 5 months later to determine predictive validity. MAIN RESULTS: :
      Reliability is reported per setting using the intraclass correlation coefficient
      (2.1) and 95% confidence intervals. Intrarater reliability: LTC 0.96 (0.93-0.98)
      right foot, 0.97 (0.95-0.98) left foot; dialysis 1.00 right and 1.00 left foot.
      Interrater reliability: LTC 0.92 (0.86-0.96) right foot, 0.93 (0.87-0.96) left
      foot; dialysis 0.83 (0.65-0.92) right foot and left foot. Predictive validity:
      Two subjects had events-1 ulcer and 1 amputation-that were associated with high
      Inlow's screening tool scores. CONCLUSION: : This study demonstrates excellent
      interrater and intrarater reliability and provides preliminary information about
      predictive validity.

PMID- 22610111
TI  - Role of a point-of-care protease activity diagnostic test in Canadian clinical
      practice: a Canadian expert consensus (c).
AB  - Nonhealing wounds (stalled, healable) challenge affected individuals, wound
      clinicians, and society. Nonhealing may result despite local factors being
      corrected. The interplay between tissue degradation, increased inflammatory
      response, and abundant protease activity is a challenging quandary. A modified
      Delphi process was utilized to investigate a protease activity test and practice
      implications.

PMID- 22610112
TI  - Evidence for interventional procedures as an adjunct therapy in the treatment of
      shingles pain.
AB  - PURPOSE: To enhance the learner's competence with knowledge of interventional
      procedures as an adjunct therapy in the treatment of shingles pain. TARGET
      AUDIENCE: This continuing education activity is intended for physicians and
      nurses with an interest in skin and wound care. OBJECTIVES: After participating
      in this educational activity, the participant should be better able to:1.
      Demonstrate knowledge of active herpes zoster (HZ) symptoms, antiviral therapy
      criteria, non-interventional medication management for HZ-related symptoms, and
      HZ-related complications including post-herpetic neuralgia (PHN).2. Apply
      knowledge of PHN interventional procedures to examples of patient care case
      scenarios. ABSTRACT: Shingles (herpes zoster) is a painful manifestation of
      infection of the dorsal root ganglia of the spine and seen as blisters or
      vesicles in linear formation, usually on the upper torso. Up to one-third of
      those afflicted will experience complications, with the most common complication
      being postherpetic neuralgia (PHN). The risk of PHN increases for each decade of
      life after age 50 years, and the pain associated with this complication has the
      potential to endure for years, be unrelenting, and decrease an individual's
      quality of life. Treatment options, including adjunct interventional procedures,
      are presented to address the common complication of PHN. Although no conclusive
      evidence base is present for the use of any particular interventional procedure
      in the treatment of acute pain or refractory pain of shingles, a number of
      therapies have been indicated to have some level of effectiveness. Standard
      therapy options in the form of oral medications and topical agents should be used
      first. For those situations of refractory pain, a referral to an interventional
      pain management specialist is warranted to explore possible adjunct procedures to
      lessen the pain of PHN. A comprehensive care management approach, incorporating
      interventional pain management procedures as an adjunct therapy, will enable
      patients to have their pain treated as effectively as possible by utilizing
      appropriate methods available.

PMID- 22610114
TI  - Electronic health record wound care checklists.

PMID- 22610115
TI  - Purification and characterization of an acidothermophilic cellulase enzyme
      produced by Bacillus subtilis strain LFS3.
AB  - In the present investigation, a microorganism hydrolyzing carboxymethylcellulose
      (CMC) was isolated and identified as Bacillus subtilis strain LFS3 by 16S rDNA
      sequence analysis. The carboxymethylcellulase (CMCase) enzyme produced by the B.
      subtilis strain LFS3 was purified by (NH4)2SO4 precipitation, ion exchange and
      gel filtration chromatography, with an overall recovery of 15 %. Native-PAGE
      analysis of purified CMCase revealed the molecular weight of enzyme to be about
      185 kDa. The activity profile of CMCase enzyme showed the optimum activity at
      temperature 60  degrees C and pH 4.0, respectively. The enzyme activity was
      induced by Na+, Mg2+, NH4+, and EDTA, whereas strongly inhibited by Hg2+ and
      Fe3+. The purified enzyme hydrolyzed CMC, filter paper, and xylan, but not p
      nitrophenyl beta-D-glucopyranoside and cellulose. Kinetic analysis of purified
      enzyme showed the K(m) value of 2.2 mg/ml. Thus, acidophilic as well as
      thermophilic nature makes this cellulase a suitable candidate for current
      mainstream biomass conversion into fuel and other industrial processes.

PMID- 22610116
TI  - Dominant missense mutations in ABCC9 cause Cantu syndrome.
AB  - Cantu syndrome is characterized by congenital hypertrichosis, distinctive facial
      features, osteochondrodysplasia and cardiac defects. By using family-based exome
      sequencing, we identified a de novo mutation in ABCC9. Subsequently, we
      discovered novel dominant missense mutations in ABCC9 in 14 of the 16 individuals
      with Cantu syndrome examined. The ABCC9 protein is part of an ATP-dependent
      potassium (K(ATP)) channel that couples the metabolic state of a cell with its
      electrical activity. All mutations altered amino acids in or close to the
      transmembrane domains of ABCC9. Using electrophysiological measurements, we show
      that mutations in ABCC9 reduce the ATP-mediated potassium channel inhibition,
      resulting in channel opening. Moreover, similarities between the phenotype of
      individuals with Cantu syndrome and side effects from the K(ATP) channel agonist
      minoxidil indicate that the mutations in ABCC9 result in channel opening. Given
      the availability of ABCC9 antagonists, our findings may have direct implications
      for the treatment of individuals with Cantu syndrome.

PMID- 22610117
TI  - Extremely low-coverage sequencing and imputation increases power for genome-wide
      association studies.
AB  - Genome-wide association studies (GWAS) have proven to be a powerful method to
      identify common genetic variants contributing to susceptibility to common
      diseases. Here, we show that extremely low-coverage sequencing (0.1-0.5*)
      captures almost as much of the common (>5%) and low-frequency (1-5%) variation
      across the genome as SNP arrays. As an empirical demonstration, we show that
      genome-wide SNP genotypes can be inferred at a mean r(2) of 0.71 using off-target
      data (0.24* average coverage) in a whole-exome study of 909 samples. Using both
      simulated and real exome-sequencing data sets, we show that association
      statistics obtained using extremely low-coverage sequencing data attain similar P
      values at known associated variants as data from genotyping arrays, without an
      excess of false positives. Within the context of reductions in sample preparation
      and sequencing costs, funds invested in extremely low-coverage sequencing can
      yield several times the effective sample size of GWAS based on SNP array data and
      a commensurate increase in statistical power.

PMID- 22610118
TI  - A model-based approach for analysis of spatial structure in genetic data.
AB  - Characterizing genetic diversity within and between populations has broad
      applications in studies of human disease and evolution. We propose a new
      approach, spatial ancestry analysis, for the modeling of genotypes in two- or
      three-dimensional space. In spatial ancestry analysis (SPA), we explicitly model
      the spatial distribution of each SNP by assigning an allele frequency as a
      continuous function in geographic space. We show that the explicit modeling of
      the allele frequency allows individuals to be localized on the map on the basis
      of their genetic information alone. We apply our SPA method to a European and a
      worldwide population genetic variation data set and identify SNPs showing large
      gradients in allele frequency, and we suggest these as candidate regions under
      selection. These regions include SNPs in the well-characterized LCT region, as
      well as at loci including FOXP2, OCA2 and LRP1B.

PMID- 22610120
TI  - A comprehensive overview of the spatial and temporal variability of apple bud
      dormancy release and blooming phenology in Western Europe.
AB  - In the current context of global warming, an analysis is required of spatially
      extensive and long-term blooming data in fruit trees to make up for insufficient
      information on regional-scale blooming changes and determinisms that are key to
      the phenological adaptation of these species. We therefore analysed blooming
      dates over long periods at climate-contrasted sites in Western Europe, focusing
      mainly on the Golden Delicious apple that is grown worldwide. On average,
      blooming advances were more pronounced in northern continental (10 days) than in
      western oceanic (6-7 days) regions, while the shortest advance was found on the
      Mediterranean coastline. Temporal trends toward blooming phase shortenings were
      also observed in continental regions. These regional differences in temporal
      variability across Western Europe resulted in a decrease in spatial variability,
      i.e. shorter time intervals between blooming dates in contrasted regions (8-10
      day decrease for full bloom between Mediterranean and continental regions).
      Fitted sequential models were used to reproduce phenological changes. Marked
      trends toward shorter simulated durations of forcing period (bud growth from
      dormancy release to blooming) and high positive correlations between these
      durations and observed blooming dates support the notion that blooming advances
      and shortenings are mainly due to faster satisfaction of the heating requirement.
      However, trends toward later dormancy releases were also noted in oceanic and
      Mediterranean regions. This could tend toward blooming delays and explain the
      shorter advances in these regions despite similar or greater warming. The
      regional differences in simulated chilling and forcing periods were consistent
      with the regional differences in temperature increases.

PMID- 22610119
TI  - Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate
      cancer.
AB  - Prostate cancer is the second most common cancer in men worldwide and causes over
      250,000 deaths each year. Overtreatment of indolent disease also results in
      significant morbidity. Common genetic alterations in prostate cancer include
      losses of NKX3.1 (8p21) and PTEN (10q23), gains of AR (the androgen receptor
      gene) and fusion of ETS family transcription factor genes with androgen
      responsive promoters. Recurrent somatic base-pair substitutions are believed to
      be less contributory in prostate tumorigenesis but have not been systematically
      analyzed in large cohorts. Here, we sequenced the exomes of 112 prostate tumor
      and normal tissue pairs. New recurrent mutations were identified in multiple
      genes, including MED12 and FOXA1. SPOP was the most frequently mutated gene, with
      mutations involving the SPOP substrate-binding cleft in 6-15% of tumors across
      multiple independent cohorts. Prostate cancers with mutant SPOP lacked ETS family
      gene rearrangements and showed a distinct pattern of genomic alterations. Thus,
      SPOP mutations may define a new molecular subtype of prostate cancer.

PMID- 22610121
TI  - NIM vs Neurosign in nerve sparing total thyroidectomy. Multicentric experience.
AB  - INTRODUCTION: Injury to cranial nerve represents 5% of negligence litigation
      against general surgeons and of all malpractice jury verdicts in endocrine
      surgery 60% accounts for recurrent nerve injuries and 15% for anoxic brain
      injuries from RLN injuries, unrecognized post-operatively. During Total
      Thyroidectomy is reported an incidence of failure to find the nerve in 5- 18% of
      cases and if we think that routine identification of the RLN during thyroid
      surgery has reduced the injury rate from 10% to less than 4% and that the
      incidence of nerve paralysis was 3 to 4 times greater in cases where the nerve
      was not exposed than in cases where was routinely exposed, then we understand the
      importance of a clear identification during every thyroid dissection MATERIALS
      AND METHODS: 880 Total Thyroidectomies during the last 4 years, since Jannuary
      2007 until December 2010, (610 F, 270 M; mean age 44,5 years old, range 14-83).
      All patients were examined pre and postoperatively (1-6 months after) by direct
      laryngoscopy or laryngofibroscopy to check vocal cord mobility (medium follow up
      25.5 months range 3-50 months). The Authors reviewed charts from two randomized
      groups, selected by a double blind, statistically designed study and again
      compared in a multivariate analysis (Stat 2004 ltd): 1) 480 total sutureless
      thyroidectomies, performed during the previous year with continuous intra
      operative nerve monitoring using dedicated endotracheal tube with a last
      generation Nerve Integrity Monitor Pulse II (N.I.M. pulse II(r)) 2) 400 total
      sutureless thyroidectomies: performed with continuous intra-operative nerve
      monitoring using dedicated Laryngeal Electrode, a self-adhesive device designed
      to fit onto standard reinforced endotracheal tubes (Neurosign(r) 1040 - 4 Channel
      EMG) RESULTS: There were no statistically significative difference between the
      two groups for distribution of age, sex, epidemiological characteristics, type of
      pathology etc. The incidence of major complications in thyroid surgery in the
      first two groups (total Thyroidectomy performed by NIM and by Neurosign), as well
      as compared with the data of the literature are absolutely overimposable; only
      significative difference is a reduction of the costs in the second group
      (Neurosign). The 1st group (NIM) specificity is 90.2% (433/480). There were 6
      cases of temporary RLN paralysis (temporary paralysis rate: 1.25 % of patients),
      3 true positive and 3 false negative. Finally there were 3 cases of permanent RLN
      paralysis (0.75%), 2 truepositive and 1 false-negative developed after 10 days
      (demyelination by thermal injury). The 2nd group (Neurosign) specificity of 89 %
      (356/400). There were 6 cases of temporary RLN paralysis (rate: 1.5 %, p > 0.5),
      2 true positive, 1 false positive and 4 false negative. Finally 2 cases of
      permanent RLN paralysis (0.5% p > 0.5), 2 true-positive. DISCUSSION AND
      CONCLUSION: Our data confirm a useful application of NIM and Neurosign in thyroid
      dissection nerve prevention. We don't believe that those procedures can be useful
      for learning thyroid gland surgery, because can't preserve from an accurate
      dissection and nerve identification technique, but can only support in nerve-at
      risk thyroidectomy or during dissection can support expert surgeon's decision,
      having a clear pre-operative (post-anesthesiologist) and post-operative
      predictive value. Those procedures are anyway expensive and time consuming (25000
      30000 ? for the E.M.G. system and almost 200-250 ? for each dedicated
      endotracheal tube in NIM group). So Neurosign group has over-imposable results in
      terms of complications specificity and accurancy (no statistically significative
      differences), but it's a much cheaper procedure!

PMID- 22610122
TI  - Risk factors for conversion of laparoscopic cholecystectomy.
AB  - BACKGROUND: Conversion during laparoscopic cholecystectomy has adverse effects on
      operating time, postoperative morbidity and hospital costs. Identifying risk
      factors for conversion is thus important to help surgeons to plan and counsel the
      patient and arranging operating schedules accordingly. This study evaluated
      retrospectively preoperative and intraoperative risk factors for conversion in
      906 laparoscopic cholecystectomies for gallbladder calculosis. METHODS: Examined
      preoperative variables were: age, sex, obesity, arterial hypertension, diabetes,
      previous acute myocardial infarction, chronic obstructive pulmonary disease, non
      ischemic heart disease, chronic hepatitis, hepatic cirrhosis, previous
      pancreatitis, biliary colics, endoscopic retrograde cholangiopancreatography
      (ERCP) and abdominal or cardiac surgery,as well as pain, fever, a high white
      blood cell count, ultrasound signs of cholecystitis at hospitalization.
      Intraoperative variables were: adhesiolysis, associated hepatic biopsy. RESULTS:
      Twenty-five operations were converted (conversion rate: 2.76%). Factors
      significantly associated with conversion were: age over 60 years, diabetes,
      previous supramesocolic abdominal surgery, ultrasound signs of cholecystitis,
      white cell count over 9x10(3)/dl, previous acute myocardial infarction and
      preoperative ERCP, intraoperative adhesiolysis (0.001<p<0.05). CONCLUSION:
      Systematic evaluation of these factors in patients scheduled for laparoscopic
      cholecystectomy may help predict difficulties of the procedure, allow patients to
      be better informed about possible conversion, and optimize the planning of
      interventions for cases at risk.

PMID- 22610123
TI  - Tracheal necrosis, oesophageal fistula: unusual complications of thyroidectomy.
      Report of two case and literature review.
AB  - BACKGROUND: Thyroidectomy is considered a low-risk operation. The authors report
      a case of tracheal necrosis after total thyroidectomy for multinodular goiter
      with bilateral adenomas, and a case of oesophageal fistula after total
      thyroidectomy for papillary cancer. METHODS AND RESULTS: The patient with
      tracheal perforation was treated by a non operative management after clinical
      stabilization. The patient with oesophageal perforation underwent surgical
      treatment consisting of neck drain placement. Both patients are alive after 12
      months of follow-up, although the patient who had surgery for papillary cancer of
      the thyroid gland was found to have multiple diffuse liver and lung metastases.
      CONCLUSIONS: Thyroidectomy is a safe surgical procedure, but in some patients
      major complications may arise. In cases of iatrogenic tracheal or oesophageal
      perforation, conservative non-surgical or conservative surgical treatment, in
      specialized centers, results in a favourable outcome. The authors discuss the
      risk factors and management of these two rare complications.

PMID- 22610125
TI  - Synthesis of the trans-hydrindane core of dictyoxetane.
AB  - A concise, stereoselective synthesis of the trans-hydrindane core of the marine
      natural product dictyoxetane is reported, starting from a Robinson annelation
      derived bicyclic enone. A phosphorane-mediated, pinacol-like rearrangement of a
      cis-diol, via a formal 1,2-hydride shift, is used to establish the requisite
      trans ring junction. (31)P NMR supports the formation of the intermediate
      phosphorane, generated in situ from the reaction of a diol with Ph(3)PCl(2).

PMID- 22610127
TI  - The need for gas-specific "Christmas tree" connections.

PMID- 22610128
TI  - Study of the therapeutic effects of a hippotherapy simulator in children with
      cerebral palsy: a stratified single-blind randomized controlled trial.
AB  - OBJECTIVE: To investigate whether hippotherapy (when applied by a simulator)
      improves postural control and balance in children with cerebral palsy. DESIGN:
      Stratified single-blind randomized controlled trial with an independent assessor.
      Stratification was made by gross motor function classification system levels, and
      allocation was concealed. SUBJECTS: Children between 4 and 18 years old with
      cerebral palsy. INTERVENTIONS: Participants were randomized to an intervention
      (simulator ON) or control (simulator OFF) group after getting informed consent.
      Treatment was provided once a week (15 minutes) for 10 weeks. MAIN MEASURES:
      Gross Motor Function Measure (dimension B for balance and the Total Score) and
      Sitting Assessment Scale were carried out at baseline (prior to randomization),
      end of intervention and 12 weeks after completing the intervention. RESULTS:
      Thirty-eight children participated. The groups were balanced at baseline. Sitting
      balance (measured by dimension B of the Gross Motor Function Measure) improved
      significantly in the treatment group (effect size = 0.36; 95% CI 0.01-0.71) and
      the effect size was greater in the severely disabled group (effect size = 0.80;
      95% CI 0.13-1.47). The improvements in sitting balance were not maintained over
      the follow-up period. Changes in the total score of the Gross Motor Function
      Measure and the Sitting Assessment Scale were not significant. CONCLUSION:
      Hippotherapy with a simulator can improve sitting balance in cerebral palsy
      children who have higher levels of disability. However, this did not lead to a
      change in the overall function of these children (Gross Motor Function
      Classification System level V).

PMID- 22610129
TI  - Evidence for a partial epithelial-mesenchymal transition in postnatal stages of
      rat auditory organ morphogenesis.
AB  - The epithelial-mesenchymal transition (EMT) plays a crucial role in the
      differentiation of many tissues and organs. So far, an EMT was not detected in
      the development of the auditory organ. To determine whether an EMT may play a
      role in the morphogenesis of the auditory organ, we studied the spatial
      localization of several EMT markers, the cell-cell adhesion molecules and
      intermediate filament cytoskeletal proteins, in epithelium of the dorsal cochlea
      during development of the rat Corti organ from E18 (18th embryonic day) until P25
      (25th postnatal day). We examined by confocal microscopy immunolabelings on
      cryosections of whole cochleae with antibodies anti-cytokeratins as well as with
      antibodies anti-vimentin, anti-E-cadherin and anti-beta-catenin. Our results
      showed a partial loss of E-cadherin and beta-catenin and a temporary appearance
      of vimentin in pillar cells and Deiters between P8 and P10. These observations
      suggest that a partial EMT might be involved in the remodelling of the Corti
      organ during the postnatal stages of development in rat.

PMID- 22610130
TI  - Zn tolerance of novel Colocasia esculenta metallothionein and its domains in
      Escherichia coli and tobacco.
AB  - Contrary to extensive researches on the roles of metallothioneins (MTs) in metal
      tolerance of animals, the roles of plant MTs in metal tolerance are largely under
      investigation. In this study, we evaluated the functional role of type 2 MT from
      Colocasia esculenta (CeMT2b) in Zn tolerance of tobacco and E. coli cells. Under
      Zn-stress conditions, transgenic tobacco overexpressing CeMT2b displayed much
      better seedling growth, a significant decrease in the levels of H(2)O(2) and an
      increase in Zn accumulation compared with the wild type. Overexpression of CeMT2b
      in E. coli greatly enhanced Zn tolerance and Zn accumulation under Zn stresses
      compared with control cells. CeMT2b bound 5.38 +/- 0.29 atoms of Zn per protein.
      To identify a structural domain of CeMT2b for Zn binding, we investigated the
      growth of E. coli expressing each of the N-terminal, C-terminal, and central
      linker domains or a CNC motif deletion from the C-terminus of full-length CeMT2b.
      The results showed that the CNC motif is required for Zn tolerance, and the N
      terminal domain is more effective in Zn tolerance than the C-terminal domain.
      Taken together, our results provide direct evidence for functional contributions
      of CeMT2b in Zn tolerance of tobacco and E. coli cells.

PMID- 22610131
TI  - Chiral polymerization in open systems from chiral-selective reaction rates.
AB  - We investigate the possibility that prebiotic homochirality can be achieved
      exclusively through chiral-selective reaction rate parameters without any other
      explicit mechanism for chiral bias. Specifically, we examine an open network of
      polymerization reactions, where the reaction rates can have chiral-selective
      values. The reactions are neither autocatalytic nor do they contain explicit
      enantiomeric cross-inhibition terms. We are thus investigating how rare a set of
      chiral-selective reaction rates needs to be in order to generate a reasonable
      amount of chiral bias. We quantify our results adopting a statistical approach:
      varying both the mean value and the rms dispersion of the relevant reaction
      rates, we show that moderate to high levels of chiral excess can be achieved with
      fairly small chiral bias, below 10%. Considering the various unknowns related to
      prebiotic chemical networks in early Earth and the dependence of reaction rates
      to environmental properties such as temperature and pressure variations, we argue
      that homochirality could have been achieved from moderate amounts of chiral
      selectivity in the reaction rates.

PMID- 22610132
TI  - Evolution of hepatitis C virus hypervariable region 1 in chronically infected
      children.
AB  - Hepatitis C virus (HCV) quasispecies diversification plays an essential role in
      the establishment of chronic infections. Our earlier analysis of HCV population
      structure in children subjected to interferon-ribavirin treatment demonstrated
      that viral quasispecies is homogenous in patients who failed to respond to the
      therapy and heterogeneous in sustained responders. We also showed that certain
      variants of HCV hypervariable region 1 (HVR1) are conserved in non-responders. To
      better elucidate the pathways of HCV evolution, here we examined the changes of
      HVR1 in viral populations isolated from sera of eight treatment-naive pediatric
      patients. We found that HCV evolution in untreated chronically infected children
      occurs according to two pathways and results in the formation of either
      genetically homogenous or variable quasispecies. Variable populations are prone
      to quasispecies shifts. In contrast, homogenous populations are composed of
      closely related variants that undergo only minor changes. In addition, we
      observed that a phenomenon of inter-quasispecies conservation of HVR1 is
      associated with some of the homogenous HCV populations. The collected data
      suggest that there exist HVR1 variants with superior fitness, capable of
      persisting in different hosts.

PMID- 22610133
TI  - Subunit vaccine formulations based on recombinant envelope proteins of
      Chikungunya virus elicit balanced Th1/Th2 response and virus-neutralizing
      antibodies in mice.
AB  - The recent resurgence of Chikungunya virus in India and Indian Ocean Islands with
      unusual clinical severity is a matter of great public health concern. Despite the
      fact that CHIKV resurgence is associated with epidemic of unprecedented
      magnitude, none of the vaccine candidate has been approved so far. The envelope
      protein E1 and E2 being the major immunodominant structural proteins with crucial
      role in virus attachment and entry, can prove to be potential vaccine candidates.
      In the present study, the immunogenic potential of bacterially expressed CHIKE1
      and CHIKE2 recombinant proteins along with various adjuvants is reported.
      Assessment of the protective efficacy of both the vaccine formulations was
      further confirmed by both in vitro and in vivo neutralisation tests. Splenocytes
      from immunized mice, cultured in vitro when stimulated with the vaccine antigens
      revealed induction of very high levels of both pro- and anti- inflammatory
      cytokines indicating a balance of Th1 and Th2 response.

PMID- 22610134
TI  - The role of protein structural analysis in the next generation sequencing era.
AB  - Proteins are macromolecules that serve a cell's myriad processes and functions in
      all living organisms via dynamic interactions with other proteins, small
      molecules and cellular components. Genetic variations in the protein-encoding
      regions of the human genome account for >85% of all known Mendelian diseases, and
      play an influential role in shaping complex polygenic diseases. Proteins also
      serve as the predominant target class for the design of small molecule drugs to
      modulate their activity. Knowledge of the shape and form of proteins, by means of
      their three-dimensional structures, is therefore instrumental to understanding
      their roles in disease and their potentials for drug development. In this chapter
      we outline, with the wide readership of non-structural biologists in mind, the
      various experimental and computational methods available for protein structure
      determination. We summarize how the wealth of structure information, contributed
      to a large extent by the technological advances in structure determination to
      date, serves as a useful tool to decipher the molecular basis of genetic
      variations for disease characterization and diagnosis, particularly in the
      emerging era of genomic medicine, and becomes an integral component in the modern
      day approach towards rational drug development. 

PMID- 22610135
TI  - Emerging applications of single-cell diagnostics.
AB  - The performance of DNA sequencers (next generation sequencing) is rapidly
      enhanced these days, being used for genetic diagnostics. Although many phenomena
      could be elucidated with such massive genome data, it is still a big challenge to
      obtain comprehensive understanding of diseases and the relevant biology at the
      cellular level. In general terms, the data obtained to date are averages of
      ensembles of cells, but it is not certain whether the same features are the same
      inside an individual cell. Accordingly, important information may be masked by
      the averaging process. As the technologies for analyzing bio-molecular components
      in single cells are being developed, single cell analysis seems promising to
      address the current limitations due to averaging problems. Although the
      technologies for single cell analysis are still at the infant stage, the single
      cell approach has the potential to improve the accuracy of diagnosis based on
      knowledge of intra- and inter-cellular networks. In this review several
      technologies and applications (especially medical applications) of genome and
      transcriptome analysis or single cells are described. 

PMID- 22610136
TI  - A longitudinal prospective study of bleeding diathesis in Egyptian pediatric
      patients:  single-center experience.
AB  - Keeping an updated registry of bleeding disorders is crucial for planning care
      and documenting prevalence. We aimed to assess the prevalence of various bleeding
      disorders including rare inherited coagulation and platelet disorders concerning
      their clinico-epidemiological, diagnostic data and bleeding manifestations
      severity. Patients suffering from manifestations of bleeding or coagulation
      disorders presented to Hematology Clinic during 16 years were included and
      prospectively followed up. Demographics, clinical characteristics, complete blood
      count, bleeding, prothrombin and activated partial thromboplastin times, platelet
      aggregation tests and bone marrow aspiration were recorded. Overall 687 patients
      with bleeding disorders from total 2949 patients were identified. Inherited
      coagulation defects were found in 27.2%; hemophilia A (70.6%), hemophilia B
      (13.9%), factor I deficiency (2.3%), factor V deficiency (1.6%), factor X
      deficiency (4.2%), factor VII deficiency (2.6%), factor XIII deficiency (1.1%),
      combined factor deficiency (2.1%) and unclassified coagulation disorders in 1.6%
      of studied patients. Overall 72.7% had diagnosed with platelet disorders; immune
      thrombocytopenia was the commonest (74.8%), and inherited conditions represent
      (25.2%) in the following order: Glanzman's thrombasthenia (11.2%), von Willebrand
      disease (6.6%), Bernard-Soulier syndrome (1%) and Chediak Higashi in 0.4% and
      unclassified in 6%. Median age of diagnosis of coagulation and platelet disorders
      were 33 and 72 months. Presenting symptoms of coagulation disorders were: 25.1%
      post circumcision bleeding, 22.5% ecchymosis, 20.9% hemoarthrosis and 15%
      epistaxis. Symptoms of rare coagulation disorders were postcircumcision bleeding
      (20%), bleeding umbilical stump (20%), epistaxis (12%), hemoarthrosis (8%) and
      hematomas (4%). Presenting symptoms in rare inherited platelet disorders were
      purpura, ecchymosis, epistaxis and bleeding gums, respectively. Analysis of the
      clinico-epidemiological data of patients with bleeding disorders is a useful tool
      for monitoring and improving their quality of care.

PMID- 22610137
TI  - Recurrent pediatric thrombosis:  the effect of underlying and/or coexisting
      factors.
AB  - The objective of this study was to evaluate the underlying diseases, thrombus
      localization, and other risk factors in pediatric patients with recurrent
      thrombosis in order to obtain a sense of early awareness of the possible
      recurrences. We retrospectively evaluated both inherited and acquired
      thrombophilic risk factors in children with recurrent thrombosis that were
      diagnosed and treated at Hacettepe University, School of Medicine, Department of
      Pediatric Hematology, Ankara, Turkey. Both congenital and acquired risk factors
      associated with recurrent thrombosis, and treatment modalities were analyzed in
      detail. Among 569 children with thrombosis, 32 (5.6%) presented with recurrent
      thrombosis. Median age at first presentation in these 32 patients [11 women
      (34.4%) and 21 men (65.6%)] was 132 months. In all, 29 (90.6%) of the 32 patients
      had an underlying chronic disorder: the most common of which was congenital heart
      disease [n = 11 (34.4%)]. At presentation intracardiac localization, including
      the entrance of the inferior and superior vena cava, was observed in 10 of the
      patients (31.2%). Thrombosis recurred at the same location in 15 (47%) patients
      and at a different location in 17 (53%). Median time interval between the first
      and second episode of thrombosis was 6.5 months (range: 1-180 months).
      Considering both acquired and congenital thrombophilic factors, three (9.3%)
      patients, four (12.5%) patients, and 14 (43.8%) patients had five, four, and
      three risk factors, respectively. More than half of the patients had elevated
      plasma FVIII (>150 IU/dl) and D-dimer (>0.5 mg/ml) levels. Thrombectomy was
      performed in three patients with organized, chronic intracardiac thrombus. Tissue
      plasminogen activator (t-PA) was used more frequently to treat recurrence than
      the first event (15.6 vs. 28.1%) and consequently the complete resolution rate
      was higher (40 vs. 77.7%) at the second event. Thrombi partially resolved in 11
      of the patients during the initial episode and in 10 patients during recurrence
      (34 vs. 32%). In all, 29 (87.5%) patients were using prophylaxis at the time of
      recurrence. [coumadin (n = 16), low molecular weight heparin (n = 12) and aspirin
      (n = 1)]. In total, four patients (12.5%) died because of their underlying
      disorders and six (18.7%) developed postthrombotic syndrome during the follow-up.
      Recurrent thrombosis should be expected, especially in cases with congenital
      heart disease, incomplete thrombus resolution, and elevated plasma FVIII/D-dimer
      levels. In the light of this knowledge we suggest aggressive treatment for
      pediatric patients with a high risk of recurrent thrombosis.

PMID- 22610138
TI  - The ultrasound frequency determines the degree of intrinsic coagulation
      activation.
AB  - Diagnostic ultrasound activates intrinsic coagulation. The aim of the present
      work was to quantify the action of different ultrasound frequencies on the
      contact phase of human blood coagulation. Pooled normal citrated platelet-poor
      plasma in 2 ml aliquots in polypropylene monovettes was exposed to diagnostic
      ultrasound, changing the ultrasound frequency from 17 to 15 to 12 to 8 to 7 MHz
      (at an intensity of 1.1 MI). After 0-2 min (23 degrees C), 400 MUl samples were
      withdrawn and placed into polypropylene Eppendorf cups. Forty microliters of
      plasma sample was pipetted into U-wells polystyrene microtiter plates of high
      purity (Brand781600). Immediately thereafter, the recalcified coagulation
      activity assay (RECA) was performed. Seventeen megahertz ultrasound exposure was
      the weakest activator of intrinsic coagulation of all frequencies tested: even 2
      min of exposure at 23 degrees C enhanced F2a generation by only about three-fold.
      The shorter the ultrasound exposure, the better the action against intrinsic
      hemostasis: 0.5 min of ultrasound exposure at 23 degrees C induced less than two
      fold thrombin generation in all frequencies tested. One minute ultrasound
      exposure (23 degrees C) triggered intrinsic coagulation strongest at 8 MHz,
      showing an approximately four-fold increase in F2a generation. A 1.5 min of
      ultrasound exposure (23 degrees C) triggered coagulation strongest at 7 MHz,
      showing an approximately 14-fold increase in F2a generation. Two minute of
      ultrasound exposure (23 degrees C) triggered coagulation strongest at 15 MHz,
      showing an approximately 18-fold increase in F2a generation. Ultrasound has to be
      considered as a potential inducer of pathologic systemic coagulation. Patients at
      risk for increased coagulation activation and/or liver insufficiency should be
      protected with low molecular weight heparin, if a prolonged ultrasound diagnostic
      is planned. Ultrasound frequencies of about 17 MHz are the weakest activators of
      intrinsic coagulation. Ultrasound frequencies of about 7 MHz might be used for
      therapeutic induction of coagulation activation, such as in patients with severe
      cerebral or hepatic hemorrhages.

PMID- 22610139
TI  - TA-2, a thrombin-like enzyme from the Chinese white-lipped green pitviper
      (Trimeresurus albolabris):  isolation, biochemical and biological
      characterization.
AB  - Through three chromatographic steps, a new thrombin-like enzyme (TLE), named TA
      2, from the venom of the Chinese white-lipped green pitviper (Trimeresurus
      albolabris) has been isolated and purified to homogeneity. TA-2 was a single
      chain glycoprotein with about 6% sugar, pI 3.9 and a molecular weight of 38.8 kD.
      Its N-terminal sequence (VVGGDECNIN) showed high sequence conformity with many
      other TLEs. In vitro, it coagulated bovine fibrinogen (108.6 NIH units/mg) and
      cleaved the Aalpha and Bbeta chains of bovine fibrinogen-releasing fibrinopeptide
      A and B, but did not degrade bovine fibrin; displayed high stability at different
      temperature, pH, and presence of several divalent cations and inhibitors; also
      exhibited strong activity towards casein (192.3 units/mg) and high esterase
      activity upon Nalpha-p-tosyl-L-arginine methyl ester (11 units/mg); and behaved
      as a promoter to platelet aggregation induced by ADP or collagen. In vivo, TA-2
      caused dose-dependent prolongation of bleeding time in mice, but had no
      hemorrhagic and edema-inducing activities even at high concentrations.

PMID- 22610140
TI  - Notch-RBP-J signaling regulates the transcription factor IRF8 to promote
      inflammatory macrophage polarization.
AB  - Emerging concepts suggest that the functional phenotype of macrophages is
      regulated by transcription factors that define alternative activation states. We
      found that RBP-J, the main nuclear transducer of signaling via Notch receptors,
      augmented Toll-like receptor 4 (TLR4)-induced expression of key mediators of
      classically activated M1 macrophages and thus of innate immune responses to
      Listeria monocytogenes. Notch-RBP-J signaling controlled expression of the
      transcription factor IRF8 that induced downstream M1 macrophage-associated genes.
      RBP-J promoted the synthesis of IRF8 protein by selectively augmenting kinase
      IRAK2-dependent signaling via TLR4 to the kinase MNK1 and downstream translation
      initiation control through eIF4E. Our results define a signaling network in which
      signaling via Notch-RBP-J and TLRs is integrated at the level of synthesis of
      IRF8 protein and identify a mechanism by which heterologous signaling pathways
      can regulate the TLR-induced inflammatory polarization of macrophages.

PMID- 22610142
TI  - Diagnostic difficulties:  chronic recurrent multifocal osteomyelitis and
      lymphoma. One or two diseases?
AB  - This paper presents a case report of a 15-year-old boy admitted to the hospital
      for persistent right knee pain and limping. The clinical appearance of his
      condition was the basis on which diagnosis of chronic recurrent multifocal
      osteomyelitis was made. Continuous deterioration in the clinical status also led
      to a suspicion of the presence of other pathological processes. A bone biopsy was
      performed and the results of histopathology showed diffused large cell B
      lymphoma. Chemotherapy was initiated; nevertheless, the patient's general state
      worsened gradually and subsequent pancytopenia resulted in septicemia and
      multiorgan failure that led to the patient's death. This paper reports the
      exceptional diagnostic challenges that emerged from the obscure course of the
      disease.

PMID- 22610141
TI  - Cross-interference of RLR and TLR signaling pathways modulates antibacterial T
      cell responses.
AB  - Although the mechanisms by which innate pathogen-recognition receptors enhance
      adaptive immune responses are increasingly well understood, whether signaling
      events from distinct classes of receptors affect each other in modulating
      adaptive immunity remains unclear. We found here that the activation of cytosolic
      RIG-I-like receptors (RLRs) resulted in the selective suppression of
      transcription of the gene encoding the p40 subunit of interleukin 12 (Il12b) that
      was effectively induced by the activation of Toll-like receptors (TLRs). The RLR
      activated transcription factor IRF3 bound dominantly, relative to IRF5, to the
      Il12b promoter, where it interfered with the TLR-induced assembly of a productive
      transcription-factor complex. The activation of RLRs in mice attenuated TLR
      induced responses of the T helper type 1 cell (T(H)1 cell) and interleukin 17
      producing helper T cell (T(H)17 cell) subset types and, consequently, viral
      infection of mice caused death at sublethal doses of bacterial infection. The
      innate immune receptor cross-interference we describe may have implications for
      infection-associated clinical episodes.

PMID- 22610143
TI  - A case of bilateral, acquired, and acute dysfunction of short-wavelength
      sensitive cone systems.
AB  - To report a case of bilateral, acquired, and acute dysfunction of short
      wavelength-sensitive (SWS) cone systems. The case was a healthy 39-year-old man.
      He noticed sudden onset of bilateral abnormal color vision. Ophthalmic
      examinations revealed normal fundi in both eyes. Farnsworth panel D-15 test and
      Farnsworth-Munsell 100-hue test showed tritanopia. White-on-white static
      perimetry showed no abnormality; however, blue-on-yellow static perimetry
      detected remarkably reduced sensitivity at the lower visual field in both eyes.
      ISCEV-standard full-field electroretinograms (ERGs) were normal; however, blue-on
      yellow ERGs showed reduced amplitude of b-wave that was derived from SWS cone
      systems in both eyes. He was observed for 1 year, and no improvement in color
      vision was found during the observation. This is a unique case which showed
      bilateral, acquired, and acute dysfunction of SWS cone systems. The cause of the
      acquired tritanopia remains to be known.

PMID- 22610144
TI  - Analysis of multifocal electroretinograms from a population with type 1 diabetes
      using partial least squares reveals spatial and temporal distribution of changes
      to retinal function.
AB  - Spatial-temporal partial least squares (ST-PLS) is a multivariate statistical
      analysis that has improved the analysis of modern imaging techniques. Multifocal
      electroretinograms (mfERGs) contain a large amount of data, and averaging and
      grouping have been used to reduce the amount of data to levels that can be
      handled using traditional statistical methods. In contrast, using all acquired
      data points, ST-PLS enables statistically rigorous testing of changes in waveform
      shape and in the distributed signal related to retinal function. We hypothesise
      that ST-PLS will improve analysis of the mfERG. Two mfERG protocols, a 103
      hexagon clinical protocol and a slow-flash mfERG (sf-mfERG) protocol, were
      recorded from an adolescent population with type 1 diabetes and an age similar
      control population. The standard mfERGs were analysed using a template-fitting
      algorithm and the sf-mfERG using a signal-to-noise measure. The results of these
      traditional analysis techniques are compared with those of the ST-PLS analysis.
      Traditional analysis of the mfERG recordings revealed changes between groups for
      implicit time but not amplitude; however, the spatial location of these changes
      could not be identified. In contrast, ST-PLS detected significant changes between
      groups and displayed the spatial location of these changes on the retinal map and
      the temporal location within the mfERG waveforms. ST-PLS confirmed that changes
      to diabetic retinal function occur before the onset of clinical pathology. In
      addition, it revealed two distinct patterns of change depending on whether the
      multifocal paradigm was optimised to target outer retinal function
      (photoreceptors) or middle/inner retinal function (collector cells).

PMID- 22610146
TI  - Imidazo[1,5-a]pyridine-1-ylalkylalcohols: synthesis via intramolecular
      cyclization of N-thioacyl 1,2-aminoalcohols and their silyl ethers and molecular
      structures.
AB  - Iodine-mediated cyclization of N-thioacyl 1,2-aminoalcohols derived from aromatic
      aldehydes and ketones mainly produced bis(1-imidazo[1,5-a]pyridyl)arylmethanes,
      whereas the reaction of N-thioacyl 1,2-aminoalcohols derived from aliphatic
      aldehydes and N-thioacyl 1,2-aminoalcohols protected with a silyl group with
      iodine gave imidazo[1,5-a]pyridine-1-ylalkylalcohols as a major product.

PMID- 22610148
TI  - Soil fertility, salinity and nematode diversity influenced by Tamarix ramosissima
      in different habitats in an arid desert oasis.
AB  - The aim of this paper was to assess the influence of tamarisk shrubs on soil
      fertility, salinity and nematode communities in various habitats located in an
      arid desert-oasis region in northwest China. Three habitats were studied: sand
      dune, riparian zone and saline meadow, where tamarisk shrubs have been
      established in recent decades in order to vegetation restoration used as
      desertification control and saline land rehabilitation projects and become the
      dominant plant community. The parameters measured include soil organic carbon
      (SOC), total nitrogen, available phosphorus (P) and potassium (K), pH, salt
      component, and nematode community characteristics. Enrichment ratios (a
      comparison of the soil measurements between soils under canopy and in the open
      interspaces) for soil nutrients and salinity were used to evaluate fertility and
      salinity islands underneath the tamarisk shrubs. The soil nematode community was
      used as a biological indicator of soil condition. SOC and available P and K were
      higher beneath the plant canopy than in the open interspaces outside that canopy.
      The enrichment ratios for SOC and nutrients were highest for the sand dune
      habitat and tamarisk shrubs clearly created islands of greater salinity under the
      canopies. Nematode abundance per 100 g dry soil varied considerably between the
      locations and habitats, with the highest abundance found in sand dune and the
      lowest in saline meadow. A significantly higher nematode abundance and a lower
      trophic diversity were found in soils under the canopy compared to the soils in
      the open interspaces. With the exception of saline meadow, the abundance of
      bacterivores increased and fungivores decreased under the canopy relative to the
      open interspaces, and bacterivores dominated under the canopies in the sand dune
      and riparian habitats. The enrichment ratios for salinity were higher than for
      fertility, suggesting that improved soil fertility can not limit the impact of
      salinization beneath tamarisk shrubs. The adverse effect of salt accumulation on
      the soil environment should be taken into account when using tamarisk as
      restoration plant species, especially in saline meadow and controlling of
      tamarisk density should be considered when undertaking re-vegetation projects in
      the arid desert oasis regions.

PMID- 22610149
TI  - Recombinant human endostatin inhibits adjuvant arthritis by down-regulating VEGF
      expression and suppression of TNF-alpha, IL-1beta production.
AB  - OBJECTIVE: The aim of this study was to examine the effect of recombinant human
      endostatin (rhEndostatin) on adjuvant arthritis (AA) in rats and its possible
      mechanisms. METHODS: RhEndostatin was subcutaneously administrated to AA rats
      after immunization. The progression of AA was assessed by the macroscopic
      arthritis scoring system of paws. Histological examination of the synovial
      tissues was examined by hematoxylin and eosin staining. The expression level of
      vascular endothelial growth factor (VEGF) mRNA and proteins in the synovial
      tissues was evaluated by realtime PCR and immunohistochemistry, respectively.
      Fibroblast-like synoviocytes (FLS) were isolated from synovial tissues. Cell
      proliferation assay was evaluateded with 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyl tetrazolium bromide. The levels of tumour necrosis factor-alpha (TNF
      alpha) and interleukin-1beta (IL-1beta) in culture medium was examined by
      radioimmno assay. RESULTS: RhEndostatin attenuated the severity of arthritis on
      both second hind paw volume and polyarthritis score, as well as improved the
      arthritic status histologically in AA rats. Simultaneously, rhEndostatin can
      inhibit the expression of VEGF in synovial tissues. The proliferation of FLS and
      TNF-alpha, IL-1beta production from culture medium was significantly inhibited by
      rhEndostatin. CONCLUSION: Our data suggest that rhEndostatin inhibits adjuvant
      arthritis by down-regulating VEGF expression and suppression of TNF-alpha, IL
      1beta production.

PMID- 22610151
TI  - Development of automated image stitching system for radiographic images.
AB  - Standard X-ray images using conventional screen-film technique have a limited
      field of view that is insufficient to show the full bone structure of large hands
      on a single frame. To produce images containing the whole hand structure,
      digitized images from the X-ray films can be assembled using image stitching.
      This paper presents a new medical image stitching method that utilizes minimum
      average correlation energy filters to identify and merge pairs of hand X-ray
      medical images. The effectiveness of the proposed method is demonstrated in the
      experiments involving two databases which contain a total of 40 pairs of
      overlapping and non-overlapping hand images. The experimental results are
      compared with that of the normalized cross-correlation (NCC) method. It is found
      that the proposed method outperforms the NCC method in classifying and merging
      the overlapping and non-overlapping medical images. The efficacy of the proposed
      method is further indicated by its average execution time, which is about five
      times shorter than that of the other method.

PMID- 22610150
TI  - Helicobacter pylori promotes apoptosis, activates cyclooxygenase (COX)-2 and
      inhibits heat shock protein HSP70 in gastric cancer epithelial cells.
AB  - OBJECTIVE: Apoptosis plays an important role in the regulation of gastric
      epithelial cell number and gastrointestinal disorders induced by Helicobacter
      pylori (Hp). Heat shock proteins (HSPs) are involved in cell integrity, cell
      growth and in gastric mucosa colonized by Hp. COX-2 was implicated in Hp-induced
      carcinogenesis but the effects of this germ and CagA cytotoxin on HSP70, COX-2,
      Bax and Bcl-2 in gastric cancer epithelial cells have been little studied.
      MATERIAL AND METHODS: We determined the expression for HSP70, Bax and Bcl-2 in
      human gastric epithelial MKN7 cells incubated with live strain Hp (cagA + vacA+)
      with or without co-incubation with exogenous CagA and NS-398, the selective COX-2
      inhibitor. After 3-48 h of incubation, the expression of HSP70, COX-2, Bax and
      Bcl-2 mRNA and proteins were determined by RT-PCR and immunoprecipitation.
      RESULTS: Hp inhibited expression for HSP70 and this was significantly potentiated
      by exogenous CagA. Co-incubation of epithelial cells with Hp, without or with
      CagA increased Bax expression and simultaneously decreased expression for Bcl-2.
      The increase in COX-2 mRNA and Bax expression were significantly inhibited by NS
      398. We conclude that Hp promotes apoptosis in adenocarcinoma gastric epithelial
      cells in vitro and this is associated with activation of COX-2 and inhibition of
      HSP70.

PMID- 22610152
TI  - The physiological stress response to high-intensity sprint exercise following the
      ingestion of sodium bicarbonate.
AB  - The purpose of this study was to investigate the effects of pre-exercise
      alkalosis on the physiological stress response to high-intensity exercise. Seven
      physically active males (age 22 +/- 3 years, height 1.82 +/- 0.06 m, mass 81.3 +/
      8.4 kg and peak power output 300 +/- 22 W) performed a repeated sprint cycle
      exercise following a dose of 0.3 g kg(-1) body mass of sodium bicarbonate
      (NaHCO(3)) (BICARB), or a placebo of 0.045 g kg(-1) body mass of sodium chloride
      (PLAC). Monocyte-expressed heat shock protein 72 (HSP72) and plasma
      thiobarbituric acid reactive substances (TBARS) were significantly attenuated in
      BICARB compared to PLAC (p = 0.04 and p = 0.039, respectively), however total
      anti-oxidant capacity, the ratio of oxidised to total glutathione, cortisol,
      interleukin 6 and interleukin 8 were not significantly induced by the exercise.
      In conclusion, monocyte-expressed HSP72 is significantly increased following high
      intensity anaerobic exercise, and its attenuation following such exercise with
      the ingestion of NaHCO(3) is unlikely to be due to a decreased oxidative stress.

PMID- 22610153
TI  - Extended benefit from sequential administration of docetaxel after standard
      fluorouracil, epirubicin, and cyclophosphamide regimen for node-positive breast
      cancer: the 8-year follow-up results of the UNICANCER-PACS01 trial.
AB  - PURPOSE: The initial report from the Programme Action Concertee Sein (PACS)
      PACS01 trial demonstrated a benefit at 5 years for disease-free survival (DFS)
      and overall survival (OS) rates with the sequential administration of docetaxel
      after FEC100 (fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), and
      cyclophosphamide 500 mg/m(2)) for patients with node-positive, operable breast
      cancer. We evaluate here the impact of this regimen at 8 years. PATIENTS AND
      METHODS: Between June 1997 and March 2000, a total of 1,999 patients (age <65)
      with localized, resectable, non-pretreated, unilateral breast cancer were
      randomly assigned to receive either standard FEC100 for 6 cycles or 3 cycles of
      FEC100 followed by 3 cycles of 100 mg/m(2) docetaxel (FEC-D), both given every 21
      days. Radiotherapy was mandatory after conservative surgery and tamoxifen was
      given for 5 years to hormone receptor (HR)-positive patients. Five-year DFS was
      the trial's main endpoint. Updated 8-year survival data are presented. RESULTS:
      With a median follow-up of 92.8 months, 639 patients experienced at least one
      event. A total number of 383 deaths were registered. Eight-year DFS rates were
      65.8% with FEC alone and 70.2% with FEC-D. OS rates at 8 years were 78% with FEC
      alone and 83.2% with FEC-D. Cox regression analysis adjusted for age and number
      of positive nodes showed a 15% reduction in the relative risk of relapse and a
      25% reduction in the relative risk of death in favor of FEC-D. Significant
      relative risk reductions were observed in the HR-positive, HER2-positive, and
      Ki67 >=20% subpopulations. CONCLUSION: Benefits for DFS and OS rates with the
      sequential FEC-D regimen are fully confirmed at 8 years.

PMID- 22610154
TI  - Modulated chemotherapy according to modified comprehensive geriatric assessment
      in 100 consecutive elderly patients with diffuse large B-cell lymphoma.
AB  - Chemotherapy is associated with toxicity in elderly patients with potentially
      curable malignancies, posing the dilemma of whether to intensify therapy, thereby
      improving the cure rate, or de-escalate therapy, thereby reducing toxicity, with
      consequent risks for under- or overtreatment. Adequate tools to define doses and
      combinations have not been identified for lymphoma patients. We conducted a
      prospective trial aimed to evaluate the feasibility and efficacy of chemotherapy
      modulated according to a modified comprehensive geriatric assessment (CGA) in
      elderly (aged >=70 years) patients with diffuse large B-cell lymphoma (DLBCL). In
      June 2000 to March 2006, 100 patients were stratified using a CGA into three
      groups (fit, unfit, and frail), and they received a rituximab plus
      cyclophosphamide, doxorubicin, vincristine, and prednisone modulated in dose and
      drugs according to comorbidities and activities of daily living (ADL) and
      instrumental ADL scores. Treatment was associated with a complete response rate
      of 81% and mild toxicity: grade 4 neutropenia in 14%, anemia in 1%, and
      neurological and cardiac toxicity in 2% of patients. At a median follow-up of 64
      months, 51 patients were alive, with 5-year disease-free, overall, and cause
      specific survival rates of 80%, 60%, and 74%, respectively. Chemoimmunotherapy
      adjustments based on a CGA are associated with manageable toxicity and excellent
      outcomes in elderly patients with DLBCL. Wide use of this CGA-driven treatment
      may result in better cure rates, especially in fit and unfit patients.

PMID- 22610155
TI  - Primary mediastinal leiomyosarcoma.
AB  - Primary leiomyosarcoma of the mediastinum is a very rare malignant mesenchymal
      tumor, which may arise in the soft tissue of the mediastinum or from the great
      vessels. Due to its rarity and nonspecific clinical symptoms, the correct
      diagnosis and proper management are often delayed and not well established. We
      report a 55-year-old woman with a large right-sided mediastinal leiomyosarcoma
      with adhesion to the pericardium and right middle lobe, which was completely
      removed via right thoracotomy along with pericardial resection and right middle
      lobectomy.

PMID- 22610156
TI  - Surgical resection of primary cardiac lymphoma presenting as a huge mass: report
      of two cases.
AB  - Primary cardiac lymphoma (PCL) is a rare malignancy that is sometimes diagnosed
      at later stages because it is not associated with specific symptoms. Although
      chemotherapy is the standard for treating PCL, the value of surgical resection is
      controversial. We describe two patients who were treated by surgical resection
      and chemotherapy. Case 1 is a 37-year-old man with a history of acute lymphocytic
      leukemia and shortness of breath, and Case 2 is a 70-year-old woman with general
      fatigue. Both of them were presented at hospital. In Case 2, arrhythmic syncope
      occurred and direct current cardioversion was performed. Echocardiography showed
      a massive tumor in the right atrium and disturbed hemodynamics in both cases. The
      restricted venous return was alleviated by emergency surgery. The pathology
      report indicated primary cardiac lymphoma that was regressed by post-operative
      chemotherapy. A massive PCL should be surgically resected to prevent sudden
      death.

PMID- 22610157
TI  - Modified patch repair for bicuspid aortic valve with thickened raphe.
AB  - We report a successful repair of bicuspid aortic valve having thickened raphe
      using pericardial patch. After excising the thickened portion, the patch was sewn
      to the remaining leaflet and root. To note, the height the patch was sewn to the
      root was lowered to the equivalent level of the corresponding portion of the
      other cusp, to create symmetrical bicuspid configuration. Postoperative
      echocardiography revealed trivial aortic regurgitation with improved leaflet
      motion and transvalvular flow.

PMID- 22610158
TI  - Mitral valve repair during acute phase infective endocarditis with extensive
      destruction of the anterior leaflet rough zone and cerebral infarction.
AB  - Some reports suggest that mitral valve repair has good outcomes and may,
      therefore, be the preferred surgical approach in patients with active infective
      endocarditis (Doukas et al. in Heart 92(3):361-363, 2006); Ruttmann et al. in J
      Thorac Cardiovasc Surg 130(3):765-771, 2005; Sternik et al. in J Heart Valve Dis
      11(1):91-97, 2002). However, in cases of active infective endocarditis of the
      mitral valve, extensive destruction of valvular tissue may make reliable valve
      repair difficult. Moreover, the timing of valve repair for active infective
      endocarditis remains controversial, especially in patients having cerebral
      complications. We present a case of a 34-year-old woman who had active infective
      endocarditis of the mitral valve complicated by multiple acute cerebral
      infarctions from septic embolisation. We could successfully carry out mitral
      valve repair 36 h after the diagnosis of active infective endocarditis and
      cerebral infarction was made. Her postoperative course was uneventful, and the
      patient remained in good health without recurrence of infective endocarditis and
      neurological complications.

PMID- 22610159
TI  - Spontaneous hemo-pneumothorax in a patient with Ehlers-Danlos syndrome.
AB  - Spontaneous hemo-pneumothorax is one of the pulmonary complications of connective
      tissue disorders such as Ehlers-Danlos syndrome (EDS). Most thoracic surgeons
      overlook this fact and they consider it as primary. In the following report, we
      describe a unique case of spontaneous recurrent hemo-pneumothorax in a young
      patient with undiagnosed EDS. The aim of this presentation is to raise a high
      index of suspicion of every thoracic surgeon to include in his differential
      diagnosis, the connective tissue disorders in any case of spontaneous hemo
      pneumothorax.

PMID- 22610160
TI  - Anterior chest wall reconstruction with titanium plate sandwiched between two
      polypropylene sheets.
AB  - Extensive sternal resection carries the risk of difficult reconstruction and
      surgical complications. A 79-year-old woman underwent sternal resection and
      reconstruction for sternal chondrosarcoma. However, 18 months after the first
      operation, she developed six metastatic tumors on the anterior chest wall. She
      underwent subtotal sternectomy and rib resection, leaving a defect measuring 17 *
      14 cm. Reconstruction of the anterior chest wall using a titanium plate
      sandwiched between two polypropylene mesh sheets is described. This method is
      potentially applicable to extensive anterior chest resection, and its advantages
      compared with conventional prostheses are rigidity, flexibility, and usability.

PMID- 22610161
TI  - Pseudotumoral hydatid cyst of chest wall.
AB  - Hydatid disease is a zoonotic infection caused by Echinoccosis granulosus and our
      country was an endemic area. Osseous localization is uncommon and can be confused
      with tumor. We present a case of a hydatid cyst with rib involvement in a 57-year
      old man presented with thoracic pain and swelling mimicking chest wall tumor. We
      confirmed diagnosis only by surgical exploration and histopathology exam because
      radiology is not conclusive. Surgery remains the first choice for treatment in
      hydatid cyst disease that can remove the parasite radically. However, in osseous
      localization pre and postoperative course of albendazole for 6 months associated
      with surgery can help in sterilizing the cyst and reduce the recurrence rate.
      Hydatid cyst can involve all the thoracic structures; rib localization is rare
      and needs surgical resection for total eradication.

PMID- 22610162
TI  - Takotsubo cardiomyopathy associated with pulmonary resections after induction
      chemoradiotherapy for non-small cell lung cancer.
AB  - Takotsubo cardiomyopathy (TTC), also known as transient left ventricular (LV)
      apical ballooning syndrome, is characterized by transient LV dysfunction. We
      present the case of a 72-year-old man who was diagnosed as having TTC after
      surgery for two lung tumors. The patient was treated with induction
      chemoradiotherapy (CRT) followed by pulmonary resections for double primary non
      small cell lung cancers (NSCLC): cT4N1M0 disease in the right lung and cT2N0M0 in
      the left lung. Induction CRT was performed. A right upper lobectomy was initially
      performed, and a left upper divisionectomy was subsequently performed. At 3 days
      after the second surgery, he developed dyspnea and general fatigue accompanied by
      a T-wave inversion on electrocardiography (ECG). An echocardiogram revealed
      akinesis at the apex with a 30 % ejection fraction. He was diagnosed as having
      TTC and recovered with supportive care. This case is the first report of TTC
      occurring after tri-modality therapy for NSCLC.

PMID- 22610163
TI  - Primary intrapulmonary thymoma associated with myasthenia gravis.
AB  - Primary intrapulmonary thymomas are very rare. So far, research in the field has
      identified only 31 cases. In all databases, a total of two published articles
      describing primary intrapulmonary thymoma with myasthenia gravis were encountered
      between 1950 and 2010. We admitted a 58-year-old male patient with a mass in the
      right lower lobe of his lung. The tumor was excised, and histological findings
      were found to be consistent with Type AB thymoma. The patient was intubated due
      to respiratory distress during the postoperative period, and his acetylcholine
      receptor antibody was determined positive. He was diagnosed with myasthenia
      gravis. Pyridostigmine therapy and plasmapheresis were scheduled; yet, we could
      not begin therapy because of rapid deterioration of the patient's respiratory
      status due to myasthenia gravis and subsequently resulting in intubation
      associated pneumonia. The patient's health rapidly worsened, and he died.

PMID- 22610164
TI  - Manouguian double-valve replacement in a 6-year-old girl.
AB  - A 6-year-old girl with a diagnosis of aortic regurgitation with stenosis and
      mitral regurgitation because of short chordae was referred to us for surgery.
      Echocardiography revealed that the aortic and the mitral annular diameters were
      16 and 23 mm, respectively. The Ross procedure and mitral valvuloplasty were
      scheduled. During the procedure, we were concerned that aggressive mitral
      valvuloplasty might result in mitral stenosis. We therefore converted the
      procedure to double-valve replacement using the Manouguian technique because it
      was necessary to enlarge both the aortic and mitral annuli. In children, the
      mitral prosthetic valve in Manouguian technique may override aortic annulus
      resulting in left ventricular outflow tract obstruction (LVOTO). Thus, it is
      important to decide the mitral prosthetic valve size. Measurements of both annuli
      showed 15 and 21 mm in aortic and mitral positions, respectively. Size #18 ATS AP
      mechanical valve (ATS Medical, Inc., Minneapolis, MN, USA) and size #23 ATS
      mechanical valve were implanted. We successfully performed two sizes up in the
      aortic position and one size up in the mitral position avoiding complications
      such as coronary orifice obstruction and LVOTO. To our knowledge, this is the
      youngest patient who underwent double-valve replacement by the Manouguian
      technique.

PMID- 22610165
TI  - A case of middle mediastinal thymoma.
AB  - A 56-year-old male was referred to our clinic after an abnormality was found on
      chest X-ray films during regular health examinations. Middle mediastinal tumor
      was detected by computed tomography, he was admitted for surgical treatment. The
      tumor was removed by surgery, and a pathological diagnosis of mixed thymoma (type
      AB, the World Health Organization Classification) was made by examining the
      resected specimen. Because the tumor had invaded to its capsule, it was
      considered to be a stage II thymoma according to the Masaoka staging system.
      Postoperative radiation therapy (50 Gy) was administered to the mediastinum. The
      patient has remained disease-free and without any recurrence as of 9 years and 8
      months after the operation. We herein present our findings because middle
      mediastinal thymoma is incredibly rare.

PMID- 22610167
TI  - Dynamic activation of the key pathways: linking colitis to colorectal cancer in a
      mouse model.
AB  - An association between carcinogenesis and inflammation has long been appreciated.
      Chemically induced colitis-associated cancer (CAC) is a classical mouse model for
      investigating 'inflammation-cancer link' in the intestine. Diverse mechanisms
      behind this non-resolving inflammation model have been reported before, most of
      them were emphasized on key cancer genes, cytokines, and signal transduction
      abnormality based on prior knowledge. In this study, we dynamically and globally
      dissect the alteration of key pathways in the development from colitis to
      colorectal cancer. Striking evidence from gene expression profiling, serum
      cytokines detection, and immunohistochemistry analysis all reveals that different
      key pathways [NF-kappaB, STAT3, p38 mitogen-activated protein kinase (MAPK), and
      Wnt/beta-catenin signaling] and their target genes are hyperactive in different
      phases of the inflammation-cancer link. Nuclear factor-kappaB (NF-kappaB) and
      STAT3 signaling are hyperactive in the whole process, while p38 MAPK and Wnt/beta
      catenin signaling are only hyperactive in the beginning and ending, respectively.
      Through this unbiased system biological approach, we provide strong evidence that
      different key pathways are specifically involved in different phases, which
      bridge the gap between inflammation and cancer.

PMID- 22610166
TI  - S-adenosylmethionine decarboxylase overexpression inhibits mouse skin tumor
      promotion.
AB  - Neoplastic growth is associated with increased polyamine biosynthetic activity
      and content. Tumor promoter treatment induces the rate-limiting enzymes in
      polyamine biosynthesis, ornithine decarboxylase (ODC), and S-adenosylmethionine
      decarboxylase (AdoMetDC), and targeted ODC overexpression is sufficient for tumor
      promotion in initiated mouse skin. We generated a mouse model with doxycycline
      (Dox)-regulated AdoMetDC expression to determine the impact of this second rate
      limiting enzyme on epithelial carcinogenesis. TetO-AdoMetDC (TAMD) transgenic
      founders were crossed with transgenic mice (K5-tTA) that express the tetracycline
      regulated transcriptional activator within basal keratinocytes of the skin.
      Transgene expression in TAMD/K5-tTA mice was restricted to keratin 5 (K5) target
      tissues and silenced upon Dox treatment. AdoMetDC activity and its product,
      decarboxylated AdoMet, both increased approximately 8-fold in the skin. This
      enabled a redistribution of the polyamines that led to reduced putrescine,
      increased spermine, and an elevated spermine:spermidine ratio. Given the positive
      association between polyamine biosynthetic capacity and neoplastic growth, it was
      somewhat surprising to find that TAMD/K5-tTA mice developed significantly fewer
      tumors than controls in response to 7,12-dimethylbenz[a]anthracene/12-O
      tetradecanoylphorbol-13-acetate chemical carcinogenesis. Importantly, tumor
      counts in TAMD/K5-tTA mice rebounded to nearly equal the levels in the control
      group upon Dox-mediated transgene silencing at a late stage of tumor promotion,
      which indicates that latent viable initiated cells remain in AdoMetDC-expressing
      skin. These results underscore the complexity of polyamine modulation of tumor
      development and emphasize the critical role of putrescine in tumor promotion.
      AdoMetDC-expressing mice will enable more refined spatial and temporal
      manipulation of polyamine biosynthesis during tumorigenesis and in other models
      of human disease.

PMID- 22610168
TI  - An adaptive design to bridge the gap between Phase 2b/3 microbicide effectiveness
      trials and evidence required for licensure.
AB  - BACKGROUND: Vaginally and rectally applied microbicides are being developed to
      help prevent sexual acquisition of HIV. Due to the lack of surrogate outcomes,
      the path toward licensure typically moves directly from expanded safety studies
      to expensive Phase 2b/3 trials with rare incident infection outcomes. The need to
      confirm an initial trial's significant finding can lead to serious delays in
      implementing essential programs to reduce the spread of HIV. PURPOSE: To propose
      an adaptive design where a Phase 2b/3 study powered to detect a clinically
      meaningful effect with evidence of one trial (observing one-sided p < 0.025) is
      allowed to expand by a prespecified, feasible amount if interim data suggest the
      chance of further achieving a more robust evidence threshold (p < 0.001,
      potentially sufficient for licensure from a single trial) is promising. METHODS:
      As an example, prespecified conditional power criteria are used to determine
      whether a 90-event trial with 90% power to detect a 50% reduction in risk should
      be expanded to 130 events. Asymptotic results and simulations are used to assess
      false-positive error rates and other operating characteristics of the design.
      RESULTS: False-positive error rates can be controlled at the desired 0.025 and
      0.001 levels with appropriate choice of critical values or expansion criteria.
      The chance of achieving robust evidence can approach that of a 130-event trial
      with traditional stopping boundaries (controlling a = 0.001) but with
      substantially lower expected size for plausible effectiveness levels.
      LIMITATIONS: Conditional power calculations assume the interim estimate of effect
      is an unbiased estimate for the remainder of the trial, an assumption which may
      not hold if product adherence varies over time. Observing a measure of effect
      with p < 0.001 may not be sufficient for licensure. A decision to expand the
      trial would be informative to investigators regarding the interim effect size.
      CONCLUSIONS: A moderate increase in trial size can make the difference between a
      study with good power to detect a clinically meaningful effect and one which may
      reasonably obtain the robust evidence required for regulatory bodies and public
      health programs to consider making a new microbicide available to persons at risk
      of HIV infection. The proposed design allows for this possibility while not
      requiring investigators to make an up-front commitment to a prohibitively large
      trial.

PMID- 22610169
TI  - A brain leptin-renin angiotensin system interaction in the regulation of
      sympathetic nerve activity.
AB  - The sympathetic nervous system, leptin, and renin-angiotensin system (RAS) have
      been implicated in obesity-associated hypertension. There is increasing evidence
      for the presence of both leptin and angiotensin II receptors in several key brain
      cardiovascular and metabolic control regions. We tested the hypothesis that the
      brain RAS plays a facilitatory role in the sympathetic nerve responses to leptin.
      In rats, intracerebroventricular (ICV) administration of losartan (5 MUg)
      selectively inhibited increases in renal and brown adipose tissue (BAT)
      sympathetic nerve activity (SNA) produced by leptin (10 MUg ICV) but did not
      reduce the SNA responses to corticotrophin-releasing factor (CRF) or the
      melanocortin receptor agonist MTII. In mice with deletion of angiotensin II type
      1a receptors (AT(1a)R(-/-)), increases in renal and BAT SNA induced by leptin (2
      MUg ICV) were impaired whereas SNA responses to MTII were preserved. Decreases in
      food intake and body weight with ICV leptin did not differ in AT(1a)R(-/-) vs.
      AT(1a)R(+/+) mice. ICV leptin in rats increased AT(1a)R and angiotensin
      converting enzyme (ACE) mRNA in the subfornical organ and AT(1a)R mRNA in the
      arcuate nucleus, suggesting leptin-induced upregulation of the brain RAS in
      specific brain regions. To evaluate the role of de novo production of brain
      angiotensin II in SNA responses to leptin, we treated rats with captopril (12.5
      MUg ICV). Captopril attenuated leptin effects on renal and BAT SNA. In
      conclusion, these studies provide evidence that the brain RAS selectively
      facilitates renal and BAT sympathetic nerve responses to leptin while sparing
      effects on food intake.

PMID- 22610170
TI  - Effects of the absence of procollagen C-endopeptidase enhancer-2 on myocardial
      collagen accumulation in chronic pressure overload.
AB  - Cardiac interstitial fibrillar collagen accumulation, such as that associated
      with chronic pressure overload (PO), has been shown to impair left ventricular
      diastolic function. Therefore, insight into cellular mechanisms that mediate
      excessive collagen deposition in the myocardium is pivotal to this important area
      of research. Collagen is secreted as a soluble procollagen molecule with NH(2)-
      and COOH (C)-terminal propeptides. Cleavage of these propeptides is required for
      collagen incorporation to insoluble collagen fibrils. The C-procollagen
      proteinase, bone morphogenic protein 1, cleaves the C-propeptide of procollagen.
      Procollagen C-endopeptidase enhancer (PCOLCE) 2, an enhancer of bone morphogenic
      protein-1 activity in vitro, is expressed at high levels in the myocardium.
      However, whether the absence of PCOLCE2 affects collagen content at baseline or
      after PO induced by transverse aortic constriction (TAC) has never been examined.
      Accordingly, in vivo procollagen processing and deposition were examined in wild
      type (WT) and PCOLCE2-null mice. No significant differences in collagen content
      or myocardial stiffness were detected in non-TAC (control) PCOLCE2-null versus WT
      mice. After TAC-induced PO, PCOLCE2-null hearts demonstrated a lesser collagen
      content (PCOLCE2-null TAC collagen volume fraction, 0.41% +/- 0.07 vs. WT TAC,
      1.2% +/- 0.3) and lower muscle stiffness compared with WT PO hearts [PCOLCE2-null
      myocardial stiffness (beta), 0.041 +/- 0.002 vs. WT myocardial stiffness, 0.065
      +/- 0.001]. In addition, in vitro, PCOLCE2-null cardiac fibroblasts exhibited
      reductions in efficiency of C-propeptide cleavage, as demonstrated by increases
      in procollagen alpha1(I) and decreased levels of processed collagen alpha1(I)
      versus WT cardiac fibroblasts. Hence, PCOLCE2 is required for efficient
      procollagen processing and deposition of fibrillar collagen in the PO myocardium.
      These results support a critical role for procollagen processing in the
      regulation of collagen deposition in the heart.

PMID- 22610171
TI  - Disruption of TRPV1-mediated coupling of coronary blood flow to cardiac
      metabolism in diabetic mice: role of nitric oxide and BK channels.
AB  - We have previously shown transient receptor potential vanilloid subtype 1 (TRPV1)
      channel-dependent coronary function is compromised in pigs with metabolic
      syndrome (MetS). However, the mechanisms through which TRPV1 channels couple
      coronary blood flow to metabolism are not fully understood. We employed mice
      lacking TRPV1 [TRPV1((-/-))], db/db diabetic, and control C57BKS/J mice to
      determine the extent to which TRPV1 channels modulate coronary function and
      contribute to vascular dysfunction in diabetic cardiomyopathy. Animals were
      subjected to in vivo infusion of the TRPV1 agonist capsaicin to examine the
      hemodynamic actions of TRPV1 activation. Capsaicin (1-100 MUg.kg(-1).min(-1))
      dose dependently increased coronary blood flow in control mice, which was
      inhibited by the TRPV1 antagonist capsazepine or the nitric oxide synthase (NOS)
      inhibitor N-nitro-l-arginine methyl ester (L-NAME). In addition, the capsaicin
      mediated increase in blood flow was attenuated in db/db mice. TRPV1((-/-)) mice
      exhibited no changes in coronary blood flow in response to capsaicin.
      Vasoreactivity studies in isolated pressurized mouse coronary microvessels
      revealed a capsaicin-dependent relaxation that was inhibited by the TRPV1
      inhibitor SB366791 l-NAME and to the large conductance calcium-sensitive
      potassium channel (BK) inhibitors iberiotoxin and Penetrim A. Similar to in vivo
      responses, capsaicin-mediated relaxation was impaired in db/db mice compared with
      controls. Changes in pH (pH 7.4-6.0) relaxed coronary vessels contracted to the
      thromboxane mimetic U46619 in all three groups of mice; however, pH-mediated
      relaxation was blunted in vessels obtained from TRPV1((-/-)) and db/db mice
      compared with controls. Western blot analysis revealed decreased myocardial TRPV1
      protein expression in db/db mice compared with controls. Our data reveal TRPV1
      channels mediate coupling of myocardial blood flow to cardiac metabolism via a
      nitric oxide-dependent, BK channel-dependent pathway that is corrupted in
      diabetes.

PMID- 22610172
TI  - Dexamethasone blocks the systemic inflammation of alveolar hypoxia at several
      sites in the inflammatory cascade.
AB  - Alveolar hypoxia produces a rapid and widespread systemic inflammation in rats.
      The inflammation is initiated by the release into the circulation of monocyte
      chemoattractant protein-1 (MCP-1) from alveolar macrophages (AMO) activated by
      the low alveolar Po(2). Circulating MCP-1 induces mast cell (MC) degranulation
      with renin release and activation of the local renin-angiotensin system, leading
      to microvascular leukocyte recruitment and increased vascular permeability. We
      investigated the effect of dexamethasone, a synthetic anti-inflammatory
      glucocorticoid, on the development of the systemic inflammation of alveolar
      hypoxia and its site(s) of action in the inflammatory cascade. The inflammatory
      steps investigated were the activation of primary cultures of AMO by hypoxia, the
      degranulation of MCs by MCP-1 in the mesentery microcirculation of rats, and the
      effect of angiotensin II (ANG II) on the leukocyte/endothelial interface of the
      mesentery microcirculation. Dexamethasone prevented the mesentery inflammation in
      conscious rats breathing 10% O(2) for 4 h by acting in all key steps of the
      inflammatory cascade. Dexamethasone: 1) blocked the hypoxia-induced AMO
      activation and the release of MCP-1 and abolished the increase in plasma MCP-1 of
      conscious, hypoxic rats; 2) prevented the MCP-1-induced degranulation of
      mesentery perivascular MCs and reduced the number of peritoneal MCs, and 3)
      blocked the leukocyte-endothelial adherence and the extravasation of albumin
      induced by topical ANG II in the mesentery. The effect at each site was
      sufficient to prevent the AMO-initiated inflammation of hypoxia. These results
      may explain the effectiveness of dexamethasone in the treatment of the systemic
      effects of alveolar hypoxia.

PMID- 22610173
TI  - Nitrite anion stimulates ischemic arteriogenesis involving NO metabolism.
AB  - Nitric oxide (NO) is a potential regulator of ischemic vascular remodeling, and
      as such therapies augmenting its bioavailability may be useful for the treatment
      of ischemic tissue diseases. Here we examine the effect of administering the NO
      prodrug sodium nitrite on arteriogenesis activity during established tissue
      ischemia. Chronic hindlimb ischemia was induced by permanent unilateral femoral
      artery and vein ligation. Five days postligation; animals were randomized to
      control PBS or sodium nitrite (165 MUg/kg) therapy twice daily. In situ vascular
      remodeling was measured longitudinally using SPY angiography and Microfil
      vascular casting. Delayed sodium nitrite therapy rapidly increased ischemic limb
      arterial vessel diameter and branching in a NO-dependent manner. SPY imaging
      angiography over time showed that nitrite therapy enhanced ischemic gracillis
      collateral vessel formation from the profunda femoris to the saphenous artery.
      Immunofluorescent staining of smooth muscle cell actin also confirmed that sodium
      nitrite therapy increased arteriogenesis in a NO-dependent manner. The NO prodrug
      sodium nitrite significantly increases arteriogenesis and reperfusion of
      established severe chronic tissue ischemia.

PMID- 22610174
TI  - Na+/Ca2+ exchanger-1 protects against systolic failure in the Akitains2 model of
      diabetic cardiomyopathy via a CXCR4/NF-kappaB pathway.
AB  - Diabetic cardiomyopathy is characterized, in part, by calcium handling imbalances
      associated with ventricular dysfunction. The cardiac Na(+)/Ca(2+) exchanger 1
      (NCX1) has been implicated as a compensatory mechanism in response to reduced
      contractility in the heart; however, its role in diabetic cardiomyopathy remains
      unknown. We aimed to fully characterize the Akita(ins2) murine model of type 1
      diabetes through assessing cardiac function and NCX1 regulation. The CXCL12/CXCR4
      chemokine axis is well described in its cardioprotective effects via progenitor
      cell recruitment postacute myocardial infarction; however, it also functions in
      regulating calcium dependent processes in the cardiac myocyte. We therefore
      investigated the potential impact of CXCR4 in diabetic cardiomyopathy. Cardiac
      performance in the Akita(ins2) mouse was monitored using echocardiography and in
      vivo pressure-volume analysis. The Akita(ins2) mouse is protected against
      ventricular systolic failure evident at both 5 and 12 mo of age. However, the
      preserved contractility was associated with a decreased sarco(endo)plasmic
      reticulum Ca(2+)-ATPase (SERCA2a)/phospholamban ratio and increased NCX1 content.
      Direct myocardial injection of adenovirus encoding anti-sense NCX1 significantly
      decreased NCX1 expression and induced systolic failure in the Akita(ins2) mouse.
      CXCL12 and CXCR4 were both upregulated in the Akita(ins2) heart, along with an
      increase in IkappaB-alpha and NF-kappaB p65 phosphorylation. We demonstrated that
      CXCR4 activation upregulates NCX1 expression through a NF-kappaB-dependent
      signaling pathway in the cardiac myocyte. In conclusion, the Akita(ins2) type 1
      diabetic model is protected against systolic failure due to increased NCX1
      expression. In addition, our studies reveal a novel role of CXCR4 in the diabetic
      heart by regulating NCX1 expression via a NF-kappaB-dependent mechanism.

PMID- 22610175
TI  - Parameters for pyrethroid insecticide QSAR and PBPK/PD models for human risk
      assessment.
AB  - In this review we have examined the status of parameters required by pyrethroid
      QSAR-PBPK/PD models for assessing health risks. In lieu of the
      chemical,biological, biochemical, and toxicological information developed on the
      pyrethroids since 1968, the finding of suitable parameters for QSAR and PBPK/PD
      model development was a monumental task. The most useful information obtained
      came from rat toxicokinetic studies (i.e., absorption, distribution, and
      excretion), metabolism studies with 14C-cyclopropane- and alcohol-labeled
      pyrethroids, the use of known chiral isomers in the metabolism studies and their
      relation to commercial products. In this review we identify the individual
      chiralisomers that have been used in published studies and the chiral HPLC
      columns available for separating them. Chiral HPLC columns are necessary for
      isomer identification and for developing kinetic values (Vm,, and Kin) for
      pyrethroid hydroxylation. Early investigators synthesized analytical standards
      for key pyrethroid metabolites, and these were used to confirm the identity of
      urinary etabolites, by using TLC. These analytical standards no longer exist, and
      muste resynthesized if further studies on the kinetics of the metabolism of
      pyrethroids are to be undertaken.In an attempt to circumvent the availability of
      analytical standards, several CYP450 studies were carried out using the substrate
      depletion method. This approach does not provide information on the products
      formed downstream, and may be of limited use in developing human environmental
      exposure PBPK/PD models that require extensive urinary metabolite data.
      Hydrolytic standards (i.e., alcohols and acids) were available to investigators
      who studied the carboxylesterase-catalyzed hydrolysis of several pyrethroid
      insecticides. The data generated in these studies are suitable for use in
      developing human exposure PBPK/PD models.Tissue:blood partition coefficients were
      developed for the parent pyrethroids and their metabolites, by using a published
      mechanistic model introduced by Poulin and Thiele (2002a; b) and log DpH 7.4
      values. The estimated coefficients, especially those of adipose tissue, were too
      high and had to be corrected by using a procedure in which the proportion of
      parent or metabolite residues that are unbound to plasma albumin is considered,
      as described in the GastroPlus model (Simulations Plus, Inc.,Lancaster, CA). The
      literature suggested that Km values be adjusted by multiplying Km by the
      substrate (decimal amount) that is unbound to microsomal or CYPprotein.
      Mirfazaelian et al. (2006) used flow- and diffusion-limited compartments in their
      deltamethrin model. The addition of permeability areas (PA) having diffusion
      limits, such as the fat and slowly perfused compartments, enabled the
      investigators to bring model predictions in line with in vivo data.There appears
      to be large differences in the manner and rate of absorption of the pyrethroids
      from the gastrointestinal tract, implying that GI advanced compartmental transit
      models (ACAT) need to be included in PBPK models. This is especially true of the
      absorption of an oral dose of tefluthrin in male rats, in which 3.0-6.9%,41.3
      46.3%, and 5.2-15.5% of the dose is eliminated in urine, feces, and
      bile,respectively (0-48 h after administration). Several percutaneous studies
      with the pyrethroids strongly support the belief that these insecticides are not
      readily absorbed, but remain on the surface of the skin until they are washed
      off. In one articular study (Sidon et al. 1988) the high levels of permethrin
      absorption through the forehead skin (24-28%) of the monkey was reported over a 7
      to 14-days period.Wester et al. (1994) reported an absorption of 1.9% of
      pyrethrin that had been applied to the forearm of human volunteers over a 7-days
      period.SAR models capable of predicting the binding of the pyrethroids to plasma
      and hepatic proteins were developed by Yamazaki and Kanaoka (2004), Saiakhov et
      al. (2000), Colmenarejo et al. (2001), and Colmenarejo (2003).
      QikProp(Schrodinger, LLC) was used to obtain Fu values for calculating partition
      coefficients and for calculating permeation constants (Caco-2, MDCK, and logBBB).
      ADMET Predictor (Simulations Plus Inc.) provided Vm~,x and Km values for the
      hydroxylation of drugs/pyrethroids by human liver recombinant cytochrome P450
      enzymes making the values available for possible use in PBPK/PD models.The Caco-2
      permeability constants and CYP3A4 Vmax and Km values are needed in PBPK/PD models
      with GI ACAT sub models. Modeling work by Chang et al.(2009) produced rate
      constants (kcat) for the hydrolysis of pyrethroids by rat serumcarboxylesterases.
      The skin permeation model of Potts and Guy (1992) was used topredict K, values
      for the dermal absorption of the 15 pyrethroids.The electrophysiological studies
      by Narahashi (1971) and others (Breckenridgeet al. 2009; Shafer et al. 2005;
      Soderlund et al. 2002; Wolansky and Harrill 2008)demonstrated that the mode of
      action of pyrethroids on nerves is to interfere with the changes in sodium and
      potassium ion currents. The pyrethroids, being highly lipid soluble, are bound or
      distributed in lipid bilayers of the nerve cell membrane and exert their action
      on sodium channel proteins. The rising phase of the action potential is caused by
      sodium influx (sodium activation), while the falling phase is caused by sodium
      activation being turned off, and an increase in potassium efflux(potassium
      activation). The action of allethrin and other pyrethroids is caused by an
      inhibition or block of the normal currents. An equation by Tatebayashi and
      Narahashi (1994) that describes the action of pyrethroids on sodium channels was
      found in the literature. This equation, or some variation of it, may be suitable
      for use in the PD portion of pyrethroid PBPK models.

PMID- 22610176
TI  - An evaluation of the diagnostic accuracy of the 1991 American College of Chest
      Physicians/Society of Critical Care Medicine and the 2001 Society of Critical
      Care Medicine/European Society of Intensive Care Medicine/American College of
      Chest Physicians/American Thoracic Society/Surgical Infection Society sepsis
      definition.
AB  - OBJECTIVES: Limited research has been conducted to compare the test
      characteristics of the 1991 and 2001 sepsis consensus definitions. This study
      assessed the accuracy of the two sepsis consensus definitions among adult
      critically ill patients compared to sepsis case adjudication by three senior
      clinicians. DESIGN: Observational study of patients admitted to intensive care
      units. SETTING: Seven intensive care units of an academic medical center.
      PATIENTS: A random sample of 960 patients from all adult intensive care unit
      patients between October 2007 and December 2008. INTERVENTION: None. MEASUREMENTS
      AND MAIN RESULTS: Sensitivity, specificity, and the area under the receiver
      operating characteristic curve for the two consensus definitions were calculated
      by comparing the number of patients who met or did not meet consensus definitions
      vs. the number of patients who were or were not diagnosed with sepsis by
      adjudication. The 1991 sepsis definition had a high sensitivity of 94.6%, but a
      low specificity of 61.0%. The 2001 sepsis definition had a slightly increased
      sensitivity but a decreased specificity, which were 96.9% and 58.3%,
      respectively. The areas under the receiver operating characteristic curve for the
      two definitions were not statistically different (0.778 and 0.776, respectively).
      The sensitivities and areas under the receiver operating characteristic curve of
      both definitions were lower at the 24-hr time window level than those of the
      intensive care unit stay level, though their specificities increased slightly.
      Fever, high white blood cell count or immature forms, low Glasgow coma score,
      edema, positive fluid balance, high cardiac index, low PaO2/FIO2 ratio, and high
      levels of creatinine and lactate were significantly associated with sepsis by
      both definitions and adjudication. CONCLUSIONS: Both the 1991 and the 2001 sepsis
      definition have a high sensitivity but low specificity; the 2001 definition has a
      slightly increased sensitivity but a decreased specificity compared to the 1991
      definition. The diagnostic performances of both definitions were suboptimal. A
      parsimonious set of significant predictors for sepsis diagnosis is likely to
      improve current sepsis case definitions.

PMID- 22610177
TI  - The protective profile of argon, helium, and xenon in a model of neonatal
      asphyxia in rats.
AB  - OBJECTIVE: Xenon provides neuroprotection in multiple animal models; however,
      little is known about the other noble gases. The aim of the current study was to
      compare xenon, argon, and helium neuroprotection in a neonatal asphyxia model in
      rats. DESIGN: Randomized controlled trial. SETTING: Laboratory. SUBJECTS: Seven
      day-old postnatal Sprague-Dawley rats. INTERVENTIONS: Seventy percent argon,
      helium, xenon, or nitrogen balanced with oxygen after hypoxic-ischemic brain
      injury. MEASUREMENTS AND MAIN RESULTS: Control animals undergoing moderate
      hypoxic-ischemia endured reduced neuronal survival at 7 days with impaired
      neurologic function at the juvenile age compared with naive animals. Severe
      hypoxic-ischemic damage produced a large cerebral infarction in controls. After
      moderate hypoxic-ischemia, all three noble gases improved cell survival, brain
      structural integrity, and neurologic function on postnatal day 40 compared with
      nitrogen. Interestingly, argon improved cell survival to naive levels, whereas
      xenon and helium did not. When tested against more severe hypoxic-ischemic injury
      only, argon and xenon reduced infarct volume. Furthermore, postinjury body weight
      in moderate insult was lower in the helium-treated group compared with the naive,
      control, and other noble gas treatment groups, whereas in the severe injurious
      setting, it is lower in both control and helium-treated groups than other groups.
      In the nondirectly injured hemisphere, argon, helium, and xenon increased the
      expression of Bcl-2, whereas helium and xenon increased Bcl-xL. In addition, Bax
      expression was enhanced in the control and helium groups. CONCLUSIONS: These
      studies indicate that argon and xenon provide neuroprotection against both
      moderate and severe hypoxia-ischemic brain injury likely through prosurvival
      proteins synthesis.

PMID- 22610179
TI  - Neurally adjusted ventilatory assist improves patient-ventilator interaction
      during postextubation prophylactic noninvasive ventilation.
AB  - OBJECTIVES: To compare the respective impact of pressure support ventilation and
      naturally adjusted ventilatory assist, with and without a noninvasive mechanical
      ventilation algorithm, on patient-ventilator interaction. DESIGN: Prospective 2
      month study. SETTING: Adult critical care unit in a tertiary university hospital.
      PATIENTS: Seventeen patients receiving a prophylactic postextubation noninvasive
      mechanical ventilation. INTERVENTIONS: Patients were randomly mechanically
      ventilated for 10 mins with: pressure support ventilation without a noninvasive
      mechanical ventilation algorithm (PSV-NIV-), pressure support ventilation with a
      noninvasive mechanical ventilation algorithm (PSV-NIV+), neurally adjusted
      ventilatory assist without a noninvasive mechanical ventilation algorithm (NAVA
      NIV-), and neurally adjusted ventilatory assist with a noninvasive mechanical
      ventilation algorithm (NAVA-NIV+). MEASUREMENTS AND MAIN RESULTS: Breathing
      pattern descriptors, diaphragm electrical activity, leak volume, inspiratory
      trigger delay, inspiratory time in excess, and the five main asynchronies were
      quantified. Asynchrony index and asynchrony index influenced by leaks were
      computed. Peak inspiratory pressure and diaphragm electrical activity were
      similar for each of the four experimental conditions. For both pressure support
      ventilation and neurally adjusted ventilatory assist, the noninvasive mechanical
      ventilation algorithm significantly reduced the level of leakage (p < .01).
      Inspiratory trigger delay was not affected by the noninvasive mechanical
      ventilation algorithm but was shorter in neurally adjusted ventilatory assist
      than in pressure support ventilation (p < .01). Inspiratory time in excess was
      shorter in neurally adjusted ventilatory assist and PSV-NIV+ than in PSV-NIV- (p
      < .05). Asynchrony index was not affected by the noninvasive mechanical
      ventilation algorithm but was significantly lower in neurally adjusted
      ventilatory assist than in pressure support ventilation (p < .05). Asynchrony
      index influenced by leaks was insignificant with neurally adjusted ventilatory
      assist and significantly lower than in pressure support ventilation (p < .05).
      There was more double triggering with neurally adjusted ventilatory assist.
      CONCLUSIONS: Both neurally adjusted ventilatory assist and a noninvasive
      mechanical ventilation algorithm improve patient-ventilator synchrony in
      different manners. NAVA-NIV+ offers the best compromise between a good patient
      ventilator synchrony and a low level of leaks. Clinical studies are required to
      assess the potential clinical benefit of neurally adjusted ventilatory assist in
      patients receiving noninvasive mechanical ventilation. TRIAL REGISTRATION:
      Clinicaltrials.gov Identifier NCT01280760.

PMID- 22610180
TI  - Usefulness of transcranial echography in patients with decompressive craniectomy:
      a comparison with computed tomography scan.
AB  - OBJECTIVE: To assess the agreement between computed tomography and transcranial
      sonography in patients after decompressive craniectomy. DESIGN: Prospective
      study. SETTING: The medical intensive care unit of a university-affiliated
      teaching hospital. PATIENTS: Thirty head-injured patients consecutively admitted
      to the intensive care unit of "A. Gemelli" Hospital who underwent decompressive
      craniectomy were studied. Immediately before brain cranial tomography,
      transcranial ultrasonography was performed. MEASUREMENTS AND MAIN RESULTS: The
      mean difference between computed tomography and echography in measuring the
      dislocation of midline structures was 0.3 +/- 1.6 mm (95% confidence interval 0.2
      0.9 mm; intraclass correlation coefficient, 0.979; p < .01). An excellent
      correlation was found between computed tomography and transcranial sonography in
      assessing volumes of hyperdense lesions (intraclass correlation coefficient,
      0.993; p < .01). Lesions that appear hypodense on computed tomography scan were
      divided in ischemic and late hemorrhagic. No ischemic lesion was localized on
      echography; a poor correlation was found between computed tomography and
      echography in assessing the volume of late hemorrhagic lesions (intraclass
      correlation coefficient, 0.151; p = .53). A quite good correlation between
      transcranial ultrasonography and computed tomography was found in measuring
      lateral ventricles width (intraclass correlation coefficient, 0.967; p < .01).
      Sensitivity and specificity of transcranial ultrasonography in comparison with
      computed tomography to detect the position of intracranial pressure catheter was
      100% and 78%. CONCLUSIONS: Echography may be a valid option to computed
      tomography in patients with decompressive craniectomy to assess the size of acute
      hemorrhagic lesions, to measure midline structures and the width of lateral
      ventricles, and to visualize the tip of the ventricular catheter.

PMID- 22610178
TI  - Plasma angiopoietin-2 in clinical acute lung injury: prognostic and pathogenetic
      significance.
AB  - BACKGROUND: Angiopoietin-2 is a proinflammatory mediator of endothelial injury in
      animal models, and increased plasma angiopoietin-2 levels are associated with
      poor outcomes in patients with sepsis-associated acute lung injury. Whether
      angiopoietin-2 levels are modified by treatment strategies in patients with acute
      lung injury is unknown. OBJECTIVES: To determine whether plasma angiopoietin-2
      levels are associated with clinical outcomes and affected by fluid management
      strategy in a broad cohort of patients with acute lung injury. DESIGN, SETTING,
      AND PARTICIPANTS: Plasma levels of angiopoietin-2 and von Willebrand factor (a
      traditional marker of endothelial injury) were measured in 931 subjects with
      acute lung injury enrolled in a randomized trial of fluid liberal vs. fluid
      conservative management. MEASUREMENTS AND MAIN RESULTS: The presence of infection
      (sepsis or pneumonia) as the primary acute lung injury risk factor significantly
      modified the relationship between baseline angiopoietin-2 levels and mortality (p
      = .01 for interaction). In noninfection-related acute lung injury, higher
      baseline angiopoietin-2 levels were strongly associated with increased mortality
      (odds ratio, 2.43 per 1-log increase in angiopoietin-2; 95% confidence interval,
      1.57-3.75; p < .001). In infection-related acute lung injury, baseline
      angiopoietin-2 levels were similarly elevated in survivors and nonsurvivors;
      however, patients whose plasma angiopoietin-2 levels increased from day 0 to day
      3 had more than double the odds of death compared with patients whose
      angiopoietin-2 levels declined over the same period of time (odds ratio, 2.29;
      95% confidence interval, 1.54-3.43; p < .001). Fluid-conservative therapy led to
      a 15% greater decline in angiopoietin-2 levels from day 0 to day 3 (95%
      confidence interval, 4.6-24.8%; p = .006) compared with fluid-liberal therapy in
      patients with infection-related acute lung injury. In contrast, plasma levels of
      von Willebrand factor were significantly associated with mortality in both
      infection-related and noninfection-related acute lung injury and were not
      affected by fluid therapy. CONCLUSIONS: Unlike von Willebrand factor, plasma
      angiopoietin-2 has differential prognostic value for mortality depending on the
      presence or absence of infection as an acute lung injury risk factor. Fluid
      conservative therapy preferentially lowers plasma angiopoietin-2 levels over time
      and thus may be beneficial in part by decreasing endothelial inflammation.

PMID- 22610182
TI  - Acetyl salicylic acid usage and mortality in critically ill patients with the
      systemic inflammatory response syndrome and sepsis.
AB  - OBJECTIVE: Low doses of acetyl salicylic acid, acting through 15-epi-lipoxin A4,
      have been shown to be anti-inflammatory in human studies. The manifold effects of
      acetyl salicylic acid on human physiology potentially may benefit patients with
      the systemic inflammatory response syndrome after sepsis or tissue trauma. We
      sought to determine whether acetyl salicylic acid administration at the time of
      development of systemic inflammatory response syndrome is associated with reduced
      mortality. DESIGN: Retrospective cohort study of consecutive intensive care unit
      admissions between April 2000 and November 2009. SETTING: Australian tertiary
      referral center. PATIENTS: Seven-thousand nine-hundred forty-five intensive care
      unit admissions examined. MEASUREMENTS AND MAIN RESULTS: The probability of in
      hospital death during admissions in which individuals were identified as having
      systemic inflammatory response syndrome or sepsis was analyzed according to
      whether they were administered acetyl salicylic acid. Propensity analysis that
      matched all patients for their probability of being prescribed acetyl salicylic
      acid was undertaken. Among 5523 patients with a first episode of systemic
      inflammatory response syndrome, 2082 were administered acetyl salicylic acid in a
      24-hr period around the time of systemic inflammatory response syndrome
      recognition. Propensity analysis showed a 10.9% mortality for acetyl salicylic
      acid users and 17.2% mortality in the propensity-matched nonusers (absolute risk
      difference -6.2%; 95% confidence interval -9.5% to -3.5%). Propensity matching
      also found that acetyl salicylic acid administration was associated with
      increased risk of renal injury (6.2% vs. 2.9%; absolute risk difference 13.3%;
      95% confidence interval 2.5% to 5.0%). In the 970 patients with proven sepsis,
      acetyl salicylic acid administration was associated with a lower mortality (27.4%
      vs. 42.2%; absolute risk difference -14.8%; 95% confidence interval -18.9% to 
      8.6%) after propensity matching. This quasi-experimental study cannot establish a
      causal association between acetyl salicylic acid and death from systemic
      inflammatory response syndrome or sepsis. Unrecognized confounders may remain but
      numerous covariates are included in the analyses. CONCLUSIONS: Our study shows a
      strong association between acetyl salicylic acid and survival in intensive care
      unit systemic inflammatory response syndrome and sepsis patients. The effect of
      acetyl salicylic acid treatment on mortality of patients with systemic
      inflammatory response syndrome and sepsis needs to be evaluated with prospective
      randomized intervention studies.

PMID- 22610183
TI  - Relationship between systemic glucose and cerebral glucose is preserved in
      patients with severe traumatic brain injury, but glucose delivery to the brain
      may become limited when oxidative metabolism is impaired: implications for
      glycemic control.
AB  - OBJECTIVE: To clarify the dynamics of glucose delivery to the brain and the
      effects of changes in blood glucose after severe traumatic brain injury. DESIGN:
      Retrospective analysis of a prospective observational cohort study. SETTING:
      Neurosurgical intensive care unit of a university hospital. PATIENTS: Seventeen
      patients with acute traumatic brain injury monitored with cerebral and
      subcutaneous microdialysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      For continuous, accurate systemic monitoring, glucose was measured in the
      interstitial space of subcutaneous adipose tissue using microdialysis, and 39
      specific episodes of spontaneous rises in glucose were identified. During these
      episodes, there was a significant positive linear relationship between systemic
      glucose levels and brain glucose concentrations measured by microdialysis (p <
      .0001). The basal lactate/pyruvate ratio, with a threshold of 25, was adopted to
      distinguish between disturbed and presumably preserved cerebral oxidative
      metabolism. Using normal vs. elevated lactate/pyruvate ratio as variable factor,
      the relationship between brain and systemic glucose during the episodes could be
      described by two significantly distinct parallel lines (p = .0001), which
      indicates a strong additive effect of subcutaneous glucose and lactate/pyruvate
      ratio in determining brain glucose. The line describing the relationship under
      disturbed metabolic conditions was lower than in presumably intact metabolic
      conditions, with a significant difference of 0.648 +/- 0.192 mM (p = .002). This
      let us to accurately predict that in this situation systemic glucose
      concentrations in the lower range of normality would result in critical brain
      glucose levels. CONCLUSIONS: The linear relationship between systemic and brain
      glucose in healthy subjects is preserved in traumatic brain-injured patients. As
      a consequence, in brain tissue where oxidative metabolism is disturbed, brain
      glucose concentrations might possibly drop below the critical threshold of 0.8 mM
      to 1.0 mM when there is a reduction in systemic glucose toward the lower limits
      of the "normal" range.

PMID- 22610184
TI  - Performance of risk-adjusted control charts to monitor in-hospital mortality of
      intensive care unit patients: a simulation study.
AB  - OBJECTIVES: Increases in case-mix adjusted mortality may be indications of
      decreasing quality of care. Risk-adjusted control charts can be used for in
      hospital mortality monitoring in intensive care units by issuing a warning signal
      when there are more deaths than expected. The aim of this study was to
      systematically assess and compare, by computer simulation, expected delay before
      a warning signal was given for an upward shift in mortality rate in intensive
      care mortality data by different risk-adjusted control charts. DESIGN: We
      compared the efficiency of the risk-adjusted P-chart, risk-adjusted Additive P
      chart, risk-adjusted Multiplicative P-chart, monthly Standardized Mortality
      Ratio, risk-adjusted Cumulative Sum, risk-adjusted Resetting Sequential
      Probability Ratio Test, and risk-adjusted Exponentially Weighted Moving Average
      control chart to detect an upward shift in mortality rate in eight different
      scenarios that varied by mortality increase factor and monthly patient volume.
      SETTING: Adult intensive care units in The Netherlands. PATIENTS: Patients
      admitted to 73 intensive care units from the Dutch National Intensive Care
      Evaluation quality registry from the year 2009. INTERVENTIONS: None.
      MEASUREMENTS: We compared the performance of the different risk-adjusted control
      charts by the median time-to-signal and the 6-month detection rate. MAIN RESULTS:
      In all eight scenarios, the risk-adjusted Exponentially Weighted Moving Average
      control chart had the shortest median time-to-signal, and in four, the highest 6
      month detection rate. The median time-to-signal for an average volume intensive
      care unit (i.e., 50 admissions per month) with an increase in mortality rate of R
      = 1.50 on the odds scale was 9 months for the risk-adjusted Exponentially
      Weighted Moving Average control chart. CONCLUSIONS: The risk-adjusted
      Exponentially Weighted Moving Average control chart signaled the fastest in most
      of the simulated scenarios and is therefore superior in detecting increases in in
      hospital mortality of intensive care patients compared to the other types of risk
      adjusted control charts.

PMID- 22610185
TI  - Neuromuscular blocking agent administration for emergent tracheal intubation is
      associated with decreased prevalence of procedure-related complications.
AB  - BACKGROUND: Emergent intubation is associated with a high rate of complications.
      Neuromuscular blocking agents are routinely used in the operating room and
      emergency department to facilitate intubation. However, use of neuromuscular
      blocking agents during emergent airway management outside of the operating room
      and emergency department is controversial. We hypothesized that the use of
      neuromuscular blocking agents is associated with a decreased prevalence of
      hypoxemia and reduced rate of procedure-related complications. METHODS: Five
      hundred sixty-six patients undergoing emergent intubations in two tertiary care
      centers, Massachusetts General Hospital, Boston, MA, and the University of
      California Los Angeles, Ronald Reagan Medical Center, Los Angeles, CA, were
      enrolled in a prospective, observational study. The 112 patients intubated during
      cardiopulmonary resuscitation were excluded, leaving 454 patients for analysis.
      All intubations were supervised by attendings trained in Critical Care Medicine.
      We measured intubating conditions, oxygen saturation during and 5 mins following
      intubation. We assessed the prevalence of procedure-related complications defined
      as esophageal intubation, traumatic intubation, aspiration, dental injury, and
      endobronchial intubation. RESULTS: The use of neuromuscular blocking agents was
      associated with a lower prevalence of hypoxemia (10.1% vs. 17.4%, p = .022) and a
      lower prevalence of procedure-related complications (3.1% vs. 8.3%, p = .012).
      This association persisted in a multivariate analysis, which controlled for
      airway grade, sedation, and institution. Use of neuromuscular blocking agents was
      associated with significantly improved intubating conditions (laryngeal view, p =
      .014; number of intubation attempts, p = .049). After controlling for the number
      of intubation attempts and laryngoscopic view, muscle relaxant use is an
      independent predictor of complications associated with emergency intubation (p =
      .037), and there is a trend towards improvement of oxygenation (p = .07).
      CONCLUSION: The use of neuromuscular blocking agents, when used by intensivists
      with a high level of training and experience, is associated with a decrease in
      procedure-related complications.

PMID- 22610181
TI  - An observational study fluid balance and patient outcomes in the Randomized
      Evaluation of Normal vs. Augmented Level of Replacement Therapy trial.
AB  - OBJECTIVE: To examine associations between mean daily fluid balance during
      intensive care unit study enrollment and clinical outcomes in patients enrolled
      in the Randomized Evaluation of Normal vs. Augmented Level (RENAL) replacement
      therapy study. DESIGN: Statistical analysis of data from multicenter, randomized,
      controlled trials. SETTING: Thirty-five intensive care units in Australia and New
      Zealand. PATIENTS: Cohort of 1453 patients enrolled in the RENAL study.
      INTERVENTIONS: We analyzed the association between daily fluid balance on
      clinical outcomes using multivariable logistic regression, Cox proportional
      hazards, time-dependent analysis, and repeated measure analysis models.
      MEASUREMENTS AND MAIN RESULTS: During intensive care unit stay, mean daily fluid
      balance among survivors was -234 mL/day compared with +560 mL/day among
      nonsurvivors (p < .0001). Mean cumulative fluid balance over the same period was 
      1941 vs. +1755 mL (p = .0003). A negative mean daily fluid balance during study
      treatment was independently associated with a decreased risk of death at 90 days
      (odds ratio 0.318; 95% confidence interval 0.24-0.43; p < .000.1) and with
      increased survival time (p < .0001). In addition, a negative mean daily fluid
      balance was associated with significantly increased renal replacement-free days
      (p = .0017), intensive care unit-free days (p < .0001), and hospital-free days (p
      = .01). These findings were unaltered after the application of different
      statistical models. CONCLUSIONS: In the RENAL study, a negative mean daily fluid
      balance was consistently associated with improved clinical outcomes. Fluid
      balance may be a target for specific manipulation in future interventional trials
      of critically ill patients receiving renal replacement therapy.

PMID- 22610186
TI  - Using standardized family members to teach communication skills and ethical
      principles to critical care trainees.
AB  - OBJECTIVE: We sought to determine the effectiveness of standardized family
      members for improving communication skills and ethical and legal knowledge of
      senior intensive care unit trainees. DESIGN: Multimodal evaluation of mixed
      methods educational intervention. SETTING: Postgraduate critical care medicine
      academic program. SUBJECTS: Postgraduate subspecialty critical care medicine
      trainees. INTERVENTION: Communication workshop featuring a short didactic session
      and four simulated family meetings using trained professionals as standardized
      family members. MEASUREMENTS: Ethical and legal knowledge and comfort with
      communication (before and after the workshop) and communication skill (during the
      workshop). MAIN RESULTS: Fifty-one postgraduate critical care medicine
      subspecialty trainees participated in the workshop over a 5-yr period. Ethical
      and legal knowledge and comfort scores improved significantly among trainees who
      participated in the workshop. Ninety percent of trainees felt that the workshop
      had met or exceeded their expectations and would recommend it to other trainees.
      Ninety-eight percent of trainees felt that the workshop had met the highest
      priority learning objectives they identified. Communication scores showed a trend
      towards improvement over the course of the workshop, although the improvements
      were not significant. Participants reflecting on the workshop >1 yr later
      overwhelmingly felt that it had prepared them for real communication challenges
      in training and practice. CONCLUSIONS: This workshop was effective for improving
      ethical and legal knowledge and comfort with communication among critical care
      medicine trainees. Participants overwhelmingly felt that it had met their
      learning needs and that it was an effective teaching tool that had prepared them
      for real communication challenges in training and practice. It could be used in a
      variety of contexts to address an often-neglected area of education.

PMID- 22610187
TI  - Safety, efficiency, and cost-effectiveness of a multidisciplinary percutaneous
      tracheostomy program.
AB  - OBJECTIVE: The frequency of bedside percutaneous tracheostomies is increasing in
      intensive care medicine, and both safety and efficiency of care are critical
      elements in continuing success of this procedure. Prioritizing patient safety, a
      tracheostomy team was created at our institution to provide bedside expertise in
      surgery, anesthesiology, respiratory, and technical support. This study was
      performed to evaluate the metrics of patient outcome, efficiency of care, and
      cost-benefit analysis of the multidisciplinary Johns Hopkins Percutaneous
      Tracheostomy Program. DESIGN: A review was performed for patients who received
      tracheostomies in 2004, the year before the Johns Hopkins Percutaneous
      Tracheostomy Program was established, and those who received tracheostomies in
      2008, the year following the program's establishment. Comparative outcomes were
      evaluated, including the efficiency of procedure and intensive care unit length
      of stay, complication rate including bleeding, hypoxia, loss of airway, and a
      financial cost-benefit analysis. SETTING: Single-center, major university
      hospital. PATIENTS: The sample consisted of 363 patients who received a
      tracheostomy in the years 2004 and 2008. MEASUREMENTS AND MAIN RESULTS: The
      number of percutaneous procedures increased from 59 of 126 tracheostomy patients
      in 2004, to 183 of 237 in 2008. There were significant decreases in the
      prevalence of procedural complications, particularly in the realm of airway
      injuries and physiologic disturbances. Regarding efficiency, the structured
      program reduced the time to tracheostomy and overall procedural time. The
      intensive care unit length of stay in nonpulmonary patients and improvement in
      intensive care unit and operating room back-fill efficiency contributed to an
      overall institutional financial benefit. CONCLUSIONS: An institutionally
      subsidized, multi-disciplinary percutaneous tracheostomy program can improve the
      quality of care in a cost-effective manner by decreasing the incidence of
      tracheostomy complications and improving both the time to tracheostomy, duration
      of procedure, and postprocedural intensive care unit stay.

PMID- 22610188
TI  - Elderly trauma patients have high circulating noradrenaline levels but attenuated
      release of adrenaline, platelets, and leukocytes in response to increasing injury
      severity.
AB  - OBJECTIVE: High patient age is a strong predictor of poor outcome in trauma
      patients. The present study investigated the effect of age on mortality and
      biomarkers of sympathoadrenal activation, tissue, endothelial, and glycocalyx
      damage, coagulation activation/inhibition, fibrinolysis, and inflammation in
      trauma patients at admission. DESIGN: Prospective observational study. SETTING:
      Single level I trauma center. PATIENTS: Eighty adult trauma patients (>=18 yrs)
      who met criteria for full trauma team activation and had an arterial cannula.
      INTERVENTION: Blood sampling a median of 68 min (interquartile range 48-88) post
      injury. MEASUREMENTS: Data on demography, biochemistry, Injury Severity Score,
      and 30-day mortality were recorded and plasma/serum was analyzed for biomarkers
      reflecting sympathoadrenal activation (adrenaline, noradrenaline),
      tissue/endothelial cell/glycocalyx damage (histone-complexed DNA fragments,
      annexin V, thrombomodulin, syndecan-1), platelet activation (soluble CD40
      ligand), coagulation activation/inhibition (prothrombin fragment 1.2,
      thrombin/antithrombin complex, antithrombin, protein C, activated protein C,
      protein S, soluble endothelial protein C receptor, tissue factor pathway
      inhibitor, von Willebrand factor, fibrinogen, factor XIII), fibrinolysis (D
      dimer, tissue-type plasminogen activator, plasminogen activator inhibitor-1), and
      inflammation (interleukin-6, terminal complement complex). Patients were
      stratified according to the median age (46 yrs) of the full cohort. RESULTS:
      Older trauma patients had markedly higher noradrenaline (p < .001) but an
      attenuated increase in adrenaline with increasing Injury Severity Score and lower
      platelets and leukocytes (both p < .05) compared to the younger patients. Older
      patients displayed a biomarker profile suggestive of enhanced release,
      activation, and consumption of the natural anticoagulants (low antithrombin, high
      activated protein C, protein S, and tissue factor pathway inhibitor) and
      hyperfibrinolysis (high tissue-type plasminogen activator) (all p < .05 vs.
      younger patients). Age was an independent predictor of mortality (hazard ratio
      1.04 [95% confidence interval 1.01-1.07], p = .005) after adjusting for Injury
      Severity Score, prehospital Glasgow Coma Scale, and plasma catecholamines.
      CONCLUSIONS: In trauma patients, the association between age and mortality was
      confirmed. Older patients had high plasma noradrenaline but attenuated adrenaline
      release with higher Injury Severity Score, impaired platelet and leukocyte
      mobilization, enhanced consumption of anticoagulants, and hyperfibrinolysis,
      which may all contribute to the poor outcome in these patients.

PMID- 22610189
TI  - Continuous negative abdominal distension augments recruitment of atelectatic
      lung.
AB  - RATIONALE: In acute lung injury, atelectasis is common and frequently develops in
      the dependent and diaphragmatic regions. Attempts to recruit lung with positive
      pressure constitute a major aim in the management of acute respiratory distress
      syndrome but are associated with overdistension and injury in nonatelectatic
      regions. OBJECTIVE: To test the hypothesis that continuous negative abdominal
      pressure using an iron lung would augment positive end-expiratory pressure in
      recruiting atelectatic lung. METHODS AND MAIN RESULTS: An in vivo rabbit model of
      ventilator-induced lung injury was used in which a recruitment maneuver followed
      by positive end-expiratory pressure (110 cm H2O) had no effect on oxygenation.
      Addition of sustained continuous negative abdominal pressure (-5 cm H2O) to the
      positive end-expiratory pressure significantly increased the end-expired lung
      volume and PaO2 but impaired ventricular preload and cardiac output (suggested by
      echocardiography). Addition of transient (15 mins) continuous negative abdominal
      pressure resulted in comparable and lasting (60 mins) increases in PaO2.
      Sustained, but not transient, continuous negative abdominal pressure was
      associated with hemodynamic depression and lactic acidosis, which appeared
      (illustrative echocardiography, n = 2) to be caused by decreased cardiac preload.
      Computerized tomography (n = 2) suggested that continuous negative abdominal
      pressure was an effective adjunct to positive end-expiratory pressure for
      recruiting atelectasis in dependent and diaphragmatic regions. In surfactant
      depleted but noninjured lungs, sustained continuous negative abdominal pressure
      augmented lung recruitment and oxygenation in the setting of higher (but not
      lower) levels of positive end-expiratory pressure and reduced central venous
      oxygenation. CONCLUSIONS: Continuous negative abdominal pressure may be a
      potential adjunct to positive end-expiratory pressure in the recruitment of
      diaphragmatic atelectasis. The approach ultimately might be useful when ceilings
      exist on the level of desired positive end-expiratory pressure.

PMID- 22610190
TI  - Endotoxemia reduces cerebral perfusion but enhances dynamic cerebrovascular
      autoregulation at reduced arterial carbon dioxide tension.
AB  - OBJECTIVE: The administration of endotoxin to healthy humans reduces cerebral
      blood flow but its influence on dynamic cerebral autoregulation remains unknown.
      We considered that a reduction in arterial carbon dioxide tension would attenuate
      cerebral perfusion and improve dynamic cerebral autoregulation in healthy
      subjects exposed to endotoxemia. DESIGN: Prospective descriptive study. SETTING:
      Hospital research laboratory. SUBJECTS: Ten healthy young subjects (age: 32 +/- 8
      yrs [mean +/- SD]; weight: 84 +/- 10 kg; weight: 184 +/- 5 cm; body mass index:
      25 +/- 2 kg/m2) participated in the study. INTERVENTIONS: Systemic hemodynamics,
      middle cerebral artery mean flow velocity, and dynamic cerebral autoregulation
      evaluated by transfer function analysis in the very low (<0.07 Hz), low (0.07
      0.15 Hz), and high (>0.15 Hz) frequency ranges were monitored in these volunteers
      before and after an endotoxin bolus (2 ng/kg; Escherichia coli). MEASUREMENTS AND
      MAIN RESULTS: Endotoxin increased body temperature of the subjects from 36.8 +/-
      0.4 degrees C to 38.6 +/- 0.5 degrees C (p < .001) and plasma tumor necrosis
      factor-alpha from 5.6 (2.8-6.7) pg/mL to 392 (128-2258) pg/mL (p < .02).
      Endotoxemia had no influence on mean arterial pressure (95 [74-103] mm Hg vs. 92
      [78-104] mm Hg; p = .75), but increased cardiac output (8.3 [6.1-9.5] L.min(-1)
      vs. 6.0 [4.5-8.2] L.min(-1); p = .02) through an elevation in heart rate (82 +/-
      9 beats.min(-1) vs. 63 +/- 10 beats.min(-1); p < .001), whereas arterial carbon
      dioxide tension (37 +/- 5 mm Hg vs. 41 +/- 2 mm Hg; p < .05) and middle cerebral
      artery mean flow velocity (37 +/- 9 cm.sec(-1) vs. 47 +/- 10 cm.sec(-1); p < .01)
      were reduced. In regard to dynamic cerebral autoregulation, endotoxemia was
      associated with lower middle cerebral artery mean flow velocity variability (1.0
      +/- 1.0 [cm.sec(-1)] Hz vs. 2.8 +/- 1.5 [cm.sec(-1)] Hz; p < .001), reduced gain
      (0.52 +/- 0.11 cm.sec(-1) x mm Hg(-1) vs. 0.74 +/- 0.17 cm.sec(-1) x mm Hg(-1); p
      < .05), normalized gain (0.22 +/- 0.05 vs. 0.40 +/- 0.17%.%; p < .05), and higher
      mean arterial pressure-to-middle cerebral artery mean flow velocity phase
      difference (p < .05) in the low frequency range (0.07-0.15 Hz). CONCLUSIONS:
      These data support that the reduction in arterial carbon dioxide tension explains
      the improved dynamic cerebral autoregulation and the reduced cerebral perfusion
      encountered in healthy subjects during endotoxemia.

PMID- 22610191
TI  - Sepsis-induced urinary concentration defect is related to nitric oxide-dependent
      inactivation of TonEBP/NFAT5, which downregulates renal medullary solute
      transport proteins and aquaporin-2.
AB  - OBJECTIVE: Acute kidney injury associated with reduced urinary concentration is a
      frequent and severe complication during sepsis. The present study addressed the
      effect of endotoxemia on the functional and molecular mechanisms that determine
      urinary concentrating ability. Efficient urinary concentration depends on,
      amongst other factors, the expression of the Cl channel kidney-specific chloride
      channel 1 and its subunit Barttin, the urea transporter-A1, and the water channel
      aquaporin 2, all of which are regulated by the transcription factor TonEBP/NFAT5.
      DESIGN: Experimental animal and cell culture model. SETTING: University
      laboratory. SUBJECTS: Wistar rats and Madin-Darby canine kidney cells.
      INTERVENTIONS: Rats were injected with lipopolysaccharide (5 mg/kg bodyweight
      intraperitoneal) or vehicle (phosphate-buffered saline) as control. After 24 hrs,
      urine, blood, and tissue samples from various kidney zones were analyzed for
      parameters that determine urinary concentration ability. Madin-Darby canine
      kidney cells were treated under isotonic or hypertonic conditions with the nitric
      oxide donor S-nitroso-N-acetylpenicillamine. MEASUREMENTS AND MAIN RESULTS: In
      rats injected with lipopolysaccharide, urine osmolality was reduced by ~40%,
      along with medullary induction of inducible nitric oxide synthase and a dramatic
      increase in urinary nitric oxide degradation products nitrite/nitrate.
      Concomitantly, expressions of ClC-K1, Barttin, urea transporter-A1, and aquaporin
      2 were significantly lower. This was associated with the appearance of S
      nitrosylated TonEBP/NFAT5, as monitored by the biotin-switch assay and
      immunoprecipitation, and reduced TonEBP/NFAT5 DNA binding activity in the renal
      inner medulla. These results were confirmed in Madin-Darby canine kidney cells
      transfected with a reporter construct driven by the urea transporter-A promoter,
      in which the nitric oxide donor S-nitroso-N-acetylpenicillamine reduces urea
      transporter-A reporter activity under isotonic and hypertonic conditions.
      CONCLUSIONS: The present data demonstrate that lipopolysaccharide increases
      medullary nitric oxide production by iNOS induction, resulting in impairment of
      the transcriptional activity of TonEBP/NFAT5 by S-nitrosylation. The consequence
      thereof is reduced expression of TonEBP/NFAT5 target genes ClC-K1, Barttin, urea
      transporter-A1, and aquaporin 2 that are required for urinary concentration. Our
      findings may provide further insight into the molecular mechanisms underlying the
      urinary concentration defect in sepsis.

PMID- 22610192
TI  - Salutary effect of resveratrol on sepsis-induced myocardial depression.
AB  - OBJECTIVES: We hypothesized that resveratrol administration would reverse sepsis
      dependent downregulation of peroxisome proliferator activated receptor-gamma
      coactivator 1alpha, preserve mitochondrial integrity, and rescue animals from
      sepsis-induced myocardial failure. SETTING: Teaching hospital research
      laboratory. INTERVENTIONS: Cecal ligation and puncture in mice was performed to
      induce sepsis. Mice that underwent cecal ligation and puncture were randomly
      assigned to receive resveratrol (30 mg/kg or 60 mg/kg) or vehicle 1 mL sodium
      chloride 0.9% subcutaneously in the scruff of the neck directly after surgery and
      at 16, 24, and 40 hrs, respectively. MEASUREMENTS AND RESULTS: Forty-eight hrs
      after cecal ligation and puncture, cardiac performance was established using
      echocardiography. Mitochondrial integrity was evaluated with electron microscopy,
      and changes in gene expression were evaluated with microarray analysis. Survival
      at 48 hrs was just under 50% and comparable between groups. Myocardial
      contractile function significantly improved after resveratrol treatment.
      Resveratrol-treated mice developed focal areas of edema, whereas vehicle-treated
      mice developed significant, diffuse myocardial edema. Electron microscopy
      revealed widespread swollen mitochondria with ruptured outer membranes,
      autophagosomes, and vacuolation of the internal compartment, which were
      significantly attenuated in resveratrol-treated animals. Resveratrol treatment
      significantly increased cardiac expression of peroxisome proliferator-activated
      receptor-gamma coactivator 1a. Microarray analysis revealed that resveratrol
      treatment resulted in upregulation of the peroxisome proliferator-activated
      receptor-gamma coactivator gene set containing genes known to be regulated by
      this transcriptional coactivator. Our data strongly suggest that administration
      of resveratrol modulates bioenergy metabolism, substrate utilization, oxidative
      stress, and detoxification pathways associated with both mitochondrial and
      cardiac pathological conditions, but does not alter mortality from sepsis.
      CONCLUSIONS: The salutary effects of resveratrol on cecal ligation and puncture
      induced myocardial dysfunction are associated with increased peroxisome
      proliferator-activated receptor-gamma coactivator 1a abundance and function.
      Preservation of myocardial energy production capacity, prevention of secondary
      injury, mitigation of inflammation, and reversal of sepsis-induced myocardial
      remodeling are likely to underlie its beneficial effects. This however, does not
      result in improved survival.

PMID- 22610193
TI  - Tight glycemic control increases metabolic distress in traumatic brain injury: a
      randomized controlled within-subjects trial.
AB  - OBJECTIVE: To determine the effects of tight glycemic control on brain metabolism
      after traumatic brain injury using brain positron emission tomography and
      microdialysis. DESIGN: Single-center, randomized controlled within-subject
      crossover observational trial. SETTING: Academic intensive care unit. METHODS: We
      performed a prospective, unblinded randomized controlled within-subject crossover
      trial of tight (80-110 mg/dL) vs. loose (120-150 mg/dL) glycemic control in
      patients with severe traumatic brain injury to determine the effects of glycemic
      control on brain glucose metabolism, as measured by [18F] deoxy-D-glucose brain
      positron emission tomography. Brain microdialysis was done simultaneously.
      MEASUREMENTS AND MAIN RESULTS: Thirteen severely injured traumatic brain injury
      patients underwent the study between 3 and 8 days (mean 4.8 days) after traumatic
      brain injury. In ten of these subjects, global brain and gray matter tissues
      demonstrated higher glucose metabolic rates while glucose was under tight control
      as compared with loose control (3.2 +/- 0.6 vs. 2.4 + 0.4, p = .02 [whole brain]
      and 3.8 +/- 1.4 vs. 2.9 +/- 0.8, p = .05 [gray matter]). However, the responses
      were heterogeneous with pericontusional tissue demonstrating the least state
      dependent change. Cerebral microdialysis demonstrated more frequent critical
      reductions in glucose (p = .02) and elevations of lactate/pyruvate ratio (p =
      .03) during tight glycemic control. CONCLUSION: Tight glycemic control results in
      increased global glucose uptake and an increased cerebral metabolic crisis after
      traumatic brain injury. The mechanisms leading to the enhancement of metabolic
      crisis are unclear, but delivery of more glucose through mild hyperglycemia may
      be necessary after traumatic brain injury.

PMID- 22610194
TI  - Tc-99m-HL91 imaging in the early detection of neuronal injury in a neonatal rat
      model of hypoxic ischemia.
AB  - OBJECTIVE: Hypoxic-ischemic insult in newborns results in progressive neuronal
      loss. For neuroprotective therapy to be effective, it is important to identify
      high-risk neonates soon after birth. 99mTc-labeled imaging agent, Tc-99m-HL91,
      developed as a putative hypoxic reagent, has been reported to demonstrate
      increased uptake in ischemic myocardium. We hypothesized that Tc-99m-HL91 is
      sensitive for the early identification of hypoxic-ischemic injury in neonatal rat
      brains. DESIGN: Laboratory investigation. SETTING: University research
      laboratory. SUBJECTS: Sprague-Dawley rat pups. INTERVENTIONS: Postnatal day-7
      pups were divided into four groups: hypoxic-ischemia, hypoxia-only, ischemia
      only, and controls. In the early (2 hrs), intermediate (20 hrs), and late (44
      hrs) reoxygenation phases, Tc-99m-HL91 in vivo and ex vivo imaging and
      quantitative autoradiography were performed. Regions of interest were drawn to
      calculate the contrast ratio of Tc-99m-HL91 uptake between the ipsilateral and
      contralateral hemispheres. Pathology, cerebral blood flow, and blood-brain
      barrier damage were determined. MEASUREMENTS AND MAIN RESULTS: After hypoxic
      ischemia, there were very few pyknotic neurons in the early phase, many pyknotic
      neurons in the intermediate phase, and extensive neuronal loss in the late phase
      postreoxygenation. Blood-brain barrier damage occurred in the early phase,
      progressed in the intermediate phase, and became extensive in the late phase. The
      hypoxia-only and ischemia-only pups showed no neuronal or blood-brain barrier
      damage and had higher cerebral blood flow postreoxygenation compared with the
      hypoxia-ischemia pups. Regions of interest analysis of in vivo and ex vivo images
      and autoradiography revealed significantly higher Tc-99m-HL91 contrast ratio at
      early and intermediate phases, not late phase of hypoxic-ischemic group. Hypoxic
      ischemia group had significantly higher contrast ratio values in the early and
      intermediate phases than the hypoxia-only and ischemia-only groups. A contrast
      ratio value of 0.15 in the early phase on postnatal day 7 had a sensitivity of
      0.95 and specificity of 0.89 in detecting significant hypoxic-ischemic lesions on
      postnatal day 21. CONCLUSION: Tc-99m-HL91 uptake is sensitive for the early
      detection of hypoxic-ischemic injury in neonatal brains.

PMID- 22610195
TI  - Treatment of acute coronary syndrome: part 2: ST-segment elevation myocardial
      infarction.
AB  - OBJECTIVE: Familiarize clinicians with recent information regarding the diagnosis
      and treatment of ST-segment elevation myocardial infarction. DATA SOURCES: PubMed
      search and review of relevant medical literature. SUMMARY: Definition,
      pathophysiology, clinical presentation, diagnosis, and treatment of ST-segment
      elevation myocardial infarction are reviewed. CONCLUSIONS: Patients with ST
      segment elevation myocardial infarction benefit from prompt reperfusion therapy.
      Adjunctive antianginal, antiplatelet, antithrombotic, beta blocker, angiotensin
      converting enzyme inhibitor, and statin agents minimize ongoing cardiac ischemia,
      prevent thrombus propagation, and reduce the risk of recurrent cardiovascular
      events.

PMID- 22610196
TI  - Delirium screening in critically ill patients: a systematic review and meta
      analysis.
AB  - OBJECTIVE: Despite its frequency and impact, delirium in critically ill patients
      is poorly recognized. Our aim was to systematically review the accuracy of
      delirium screening instruments in critically ill patients. DATA SOURCE:
      Systematic review and meta-analysis of publications between 1966 and 2011. The
      Medline and Embase databases were searched for studies on delirium in critically
      ill patients. STUDY SELECTION: The meta-analysis was limited to studies in
      critically ill patients in intensive care units, surgical wards, or emergency
      rooms. The delirium screening tool had to be feasible in a clinical setting for
      use by a nonexpert. As the gold standard, delirium had to be diagnosed based on
      appropriate criteria by a delirium expert. DATA EXTRACTION: The outcomes assessed
      were sensitivity, specificity, likelihood ratios, and summary receiver operating
      characteristics curves. DATA SYNTHESIS: Sixteen studies covering 1,523
      participants and five screening tools were included in the systematic review. The
      pooled sensitivities and specificities of Confusion Assessment Method for the
      Intensive Care Unit for detection of delirium in critically ill patients were
      75.5% and 95.8%, and for Intensive Care Delirium Screening Checklist 80.1% and
      74.6%, respectively. All but one study was performed in a research setting, and
      that one study suggested that with routine use of the Confusion Assessment Method
      for the Intensive Care Unit, half of the patients with delirium were not
      detected. CONCLUSIONS: The Confusion Assessment Method for the Intensive Care
      Unit was the most specific bedside tool for the assessment of delirium in
      critically ill patients. However, there was significant heterogeneity of the
      results. These findings were largely obtained in research settings, and the low
      sensitivity of the Confusion Assessment Method for the Intensive Care Unit in
      routine, daily practice may limit its use as a screening test.

PMID- 22610197
TI  - Training a hospitalist workforce to address the intensivist shortage in American
      hospitals: a position paper from the Society of Hospital Medicine and the Society
      of Critical Care Medicine.

PMID- 22610198
TI  - Identifying sepsis: definitions, improved definitions, and relevance.

PMID- 22610199
TI  - Room for improvement in central venous catheter postinsertion care.

PMID- 22610200
TI  - Induced hypothermia after cardiac arrest improves cardiogenic shock.

PMID- 22610201
TI  - Argon in the fast lane: noble gases and their neuroprotective effects.

PMID- 22610202
TI  - von Willebrand factor and angiopoietin-2: toward an acute lung injury endothelial
      endophenotype?

PMID- 22610203
TI  - Ventilatory support is not as smooth as power-assisted steering--not yet.

PMID- 22610204
TI  - Bedside transcranial sonography: a promising tool for the neurointensivist.

PMID- 22610205
TI  - Fluid balance and outcome in acute kidney injury: is fluid really the best
      medicine?

PMID- 22610206
TI  - Measuring renal blood flow in acute kidney injury: finally putting the horse
      before the cart.

PMID- 22610207
TI  - How much glucose does the injured brain need?

PMID- 22610208
TI  - Parenteral nutrition: lipid (soybean) versus lipid (olive oil); same... or maybe
      not?

PMID- 22610209
TI  - Control charts: from widgets to critically ill patients.

PMID- 22610210
TI  - Neuromuscular blockade for emergent intubation: know your drugs and you will be
      more successful.

PMID- 22610211
TI  - Using standardized family members to teach end-of-life skills to critical care
      trainees.

PMID- 22610212
TI  - Implementation of a specialized tracheostomy team as a strategy for quality
      improvement.

PMID- 22610213
TI  - Is admission to and surviving the intensive care unit an outcome measure of
      optimal treatment for patients with diabetes?

PMID- 22610214
TI  - Devices that enhance the "squeeze" and "release" of heart and brain during
      cardiac arrest: it takes two to tango!

PMID- 22610215
TI  - Lung recruitment: the combined effect of pressures "North" and "South" of the
      diaphragm.

PMID- 22610216
TI  - How to regulate brain perfusion during sepsis? Breathe rapidly ....

PMID- 22610217
TI  - Mechanical ventilation in the context of a "bag-in-box" respiratory system.

PMID- 22610218
TI  - Polyuria of sepsis: bugging an osmosensor in the kidney.

PMID- 22610219
TI  - In vino veritas? Pliny the Elder.

PMID- 22610220
TI  - Volatile meets versatile: does isoflurane strike a new path to neuroprotection?

PMID- 22610221
TI  - Intracranial pressure monitoring in severe traumatic brain injury: the time for a
      randomized controlled trial is now.

PMID- 22610222
TI  - Glucose control in traumatic brain injury: extra sweetness required.

PMID- 22610223
TI  - "Hot spots" in the brain: tissue to be rescued?

PMID- 22610224
TI  - A rose is a rose is a rose?

PMID- 22610225
TI  - V1a receptor agonists: the search for clean and green alternatives to
      vasopressin.

PMID- 22610226
TI  - A beginning, not the end.

PMID- 22610228
TI  - Wake-up test and stress hormone levels in patients with brain injury: a focus on
      mechanisms involved.

PMID- 22610230
TI  - Supplemental corticosteroids after intubation using etomidate in severe sepsis
      and septic shock.

PMID- 22610232
TI  - Abandoning inhumane terminal withdrawal of ventilatory support and extubation in
      the imminently dying: the role of high-quality palliative care.

PMID- 22610234
TI  - Kynurenine and hypotension: historic perspectives.

PMID- 22610236
TI  - Clinical and economic benefits associated with the management of a nosocomial
      outbreak resulting from multidrug-resistant Klebsiella pneumoniae.

PMID- 22610238
TI  - On supplementary information: Nature Immunology is implementing new editorial
      guidelines for the supplementary material of research articles.

PMID- 22610239
TI  - Immune to addiction: the ethical dimensions of vaccines against substance abuse.
AB  - Promising advances have been made in recent years for a unique class of
      immunotherapies that use vaccination to combat substance-use disorders. Although
      such vaccines are potentially useful for addictions, they raise a variety of
      ethical and social questions.

PMID- 22610240
TI  - DOCKing innate to adaptive signaling for persistent antibody production.

PMID- 22610242
TI  - Death diverted, but to what?

PMID- 22610241
TI  - Don't mess with ERAAP!

PMID- 22610243
TI  - Tespa1: another gatekeeper for positive selection.

PMID- 22610256
TI  - Patient-reported quality of life after stereotactic ablative radiotherapy for
      early-stage lung cancer.
AB  - BACKGROUND: Deterioration in health-related quality of life (HRQOL) is frequently
      observed after surgery for stage I non-small-cell lung cancer. As stereotactic
      ablative radiotherapy (SABR) can result in local control percentages exceeding
      90%, we studied baseline and post-treatment HRQOL in SABR patients. METHODS:
      HRQOL data were collected prospectively using the European Organization for
      Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire in 382 consecutive
      patients treated with SABR. Patients were referred from 68 Dutch centers, with
      86% judged unfit for surgery, and 14% declining surgery. An SABR dose of 60 Gy
      was delivered in three-, five-, or eight treatment fractions, depending on tumor
      diameter and location. HRQOL data were available for 382 patients at baseline
      (pre-SABR), and for 282, 212, 144, 56, and 43 patients at 3, 6, 12, 18, and 24
      months post-SABR, respectively. RESULTS: Median survival was 40 months, with a 2
      year survival of 66%. Local, regional, and distant failure percentages at 2 years
      were 6%, 13%, and 22%, respectively. Mean baseline global HRQOL and physical
      functioning scores were 62.9 +/- 1.1 and 61.7 +/- 1.1, respectively. Baseline
      symptom scores were highest for dyspnea (47.1 +/- 1.7) and fatigue (37.4 +/-
      1.3). Except for a nonsignificant decrease in 2 to 3 points per year in physical
      functioning, no statistically or clinically significant worsening of any of the
      HRQOL functioning or symptom scores at any follow-up time point was observed.
      CONCLUSIONS: Patients referred for SABR have substantially worse baseline HRQOL
      scores than those reported in the surgical literature. Clinically relevant
      deteriorations in HRQOL subscale scores were not observed after SABR.

PMID- 22610250
TI  - Genetic variation in Toll-like receptors and disease susceptibility.
AB  - Toll-like receptors (TLRs) are key initiators of the innate immune response and
      promote adaptive immunity. Much has been learned about the role of TLRs in human
      immunity from studies linking TLR genetic variation with disease. First,
      monogenic disorders associated with complete deficiency in certain TLR pathways,
      such as MyD88-IRAK4 or TLR3-Unc93b-TRIF-TRAF3, have demonstrated the specific
      roles of these pathways in host defense against pyogenic bacteria and
      herpesviruses, respectively. Second, common polymorphisms in genes encoding
      several TLRs and associated genes have been associated with both infectious and
      autoimmune diseases. The study of genetic variation in TLRs in various
      populations combined with information on infection has demonstrated complex
      interaction between genetic variation in TLRs and environmental factors. This
      interaction explains the differences in the effect of TLR polymorphisms on
      susceptibility to infection and autoimmune disease in various populations.

PMID- 22610257
TI  - Postmarketing surveillance study of erlotinib in Japanese patients with non-small
      cell lung cancer (NSCLC): an interim analysis of 3488 patients (POLARSTAR).
AB  - INTRODUCTION: Interstitial lung disease (ILD) is an adverse drug reaction (ADR)
      of concern in Japanese patients with non-small-cell lung cancer (NSCLC) receiving
      erlotinib. To investigate erlotinib safety and efficacy in Japanese patients, a
      large-scale surveillance study was implemented. METHODS: All patients with
      recurrent/advanced NSCLC receiving erlotinib in Japan were enrolled (December
      2007-October 2009). During the 12-month observation period, adverse-event data
      were collected; any adverse event where erlotinib could not be excluded as a
      causative factor was termed an ADR. An independent review committee assessed ILD
      like events. Overall survival and progression-free survival were also assessed.
      Interim data were analyzed for patients registered before June 30, 2008. RESULTS:
      In total, 10,708 patients were enrolled, 3743 by June 30, 2008, with data
      available for 3488 patients. Overall ADR incidence was 81.8% (mostly grade 1/2);
      skin disorders (68.5%) including rash (63.0%) were most common. However, 81.8% of
      patients who experienced rash recovered or improved. ILD-like events, diagnosed
      by local physicians, were reported in 189 patients. The independent review
      committee confirmed ILD (all grades) in 158 patients (4.5% of interim population)
      with a mortality rate of 1.6% (55 patients). Significant ILD risk factors
      included concomitant or previous ILD, smoking history, concomitant or previous
      lung infection, and Eastern Cooperative Oncology Group performance status 2 to 4.
      Median overall survival and progression-free survival were 260 and 64 days,
      respectively. CONCLUSIONS: These interim data support the clinical benefits of
      erlotinib in Japanese NSCLC patients with no new safety signals. The risk/benefit
      balance for erlotinib in recurrent/advanced NSCLC remains favorable.

PMID- 22610258
TI  - Features and prognostic factors of large node-negative non-small-cell lung
      cancers shifted to stage II.
AB  - BACKGROUND: During the period that randomized clinical trials were establishing
      the role of adjuvant therapy in tumors larger than 5 cm without lymph-node
      invasion, which shifted from stage IB (6th TNM) to stage II (7th TNM), we derived
      the rate of shifted patients in our series and analyzed the relationship between
      specific patient- and tumor- characteristics, and clinical outcome, to identify
      putative prognostic factors. METHODS: We retrospectively collected data (age,
      sex, smoking status, type of surgery grading, and histological type) from 467
      patients who underwent radical surgery for primary 6th TNM-T2N0 non-small cell
      lung cancer patients between 1998 and 2009 at our institute. Categorical
      variables were cross-tabulated by tumor staging according to the 7th TNM edition,
      and they were tested both for association with stage and survival. RESULTS: One
      hundred and eighteen patients shifted to stage II, mainly older patients and
      patients with a sarcomatoid or a poorly differentiated carcinoma. Median overall
      survival time was significantly different across stages. Among the factors
      investigated, only the tumor dimension resulted in being statistically
      significant in multivariate analysis. CONCLUSIONS: Nearly a quarter of patients
      shifted from stage I (6th TNM) to stage II (7th TNM), raising a major need for
      information on the effects of adjuvant chemotherapy in this group of patients.
      Our findings suggest that randomized clinical trials aimed at addressing this
      topic should consider only tumor dimensions as principal selection criteria.

PMID- 22610259
TI  - EGFR array: uses in the detection of plasma EGFR mutations in non-small cell lung
      cancer patients.
AB  - INTRODUCTION: We aim to develop a simple and sensitive array-based method for the
      detection of epidermal growth factor receptor (EGFR) gene mutations in the plasma
      of non-small-cell lung cancer patients and determine its use in the follow-up of
      those on tyrosine-kinase inhibitor (TKI) therapy. METHOD: DNA from 100 MUl of
      plasma was amplified in the presence of peptide nucleic acid clamp to provide
      single-stranded template for the allele-specific arrayed primer extension
      reaction, incorporating cyanine-5-deoxycytidine triphosphate in the newly
      synthesized strands. The fluorescent product was visualized by laser at 670 nm.
      RESULTS: Eleven different types of EGFR TKI drug-sensitive mutants (SM) were
      identified in plasma-DNA from 46 of 51 patients. Five patients carried only wild
      type sequence. Plasma-DNA finding was concordant in 36 of 37 cases with tumor
      sequencing data. This method could detect as little as 62.5 copies of mutant
      L858R; 125 copies of E709K + G719A or 625 copies of del 746-750 in the presence
      of 100,000 copies of wild-type EGFR. In 21 patients on longitudinal follow-up for
      up to 18 months, SM was found in all initial plasma samples, except for three
      samples collected after recent chemotherapy. Nine of 16 patients (56%) who
      responded to TKI had undetectable plasma EGFR mutant. SM was present concurrently
      with drug-resistant mutant in 44% of patients with disease progression while on
      TKI, the remaining 56% might have other mechanisms of resistance. CONCLUSION: The
      EGFR array provides a sensitive, inexpensive, and robust method for monitoring
      non-small-cell lung cancer patients' response to TKI, and obviates the need of
      repeated lung biopsy.

PMID- 22610260
TI  - Synthesis, characterization and cation-induced dimerization of new aza-crown
      ether-appended metalloporphyrins.
AB  - New metalloporphyrins bearing one or two aryl-aza-crown ether moieties at meso
      positions have been synthesized using a palladium catalyzed amination reaction
      and fully characterized by spectral techniques. X-Ray structural data have been
      presented for the zinc and copper complexes of mono-substituted aza-crown ether
      appended metalloporphyrins. UV-Vis and (1)H NMR spectroscopic studies showed that
      addition of K(+) cations to a solution of monomeric aza-crowned porphyrins in
      CHCl(3)/MeOH led to cation-induced dimerization of these porphyrins, whereas
      addition of Na(+) cations yielded a monomeric complex. Axial coordination of the
      exobidentate ligand (DABCO) to zinc complexes of aza-crowned porphyrins and
      following binding metal ions led to formation of sandwich complexes with high
      stability constants.

PMID- 22610261
TI  - Cortisol is responsible for positive and negative effects in the ovarian
      maturation induced by the exposure to acute stressors in Nile tilapia,
      Oreochromis niloticus.
AB  - The aim of the present study was to evaluate the effect of acute stress and
      cortisol injection on oocyte final maturation process in female Nile tilapia
      (Oreochromis niloticus). Handling followed by a prophylactic treatment (0.3 mL L(
      1) H(2)O(2), 5 g L(-1) NaCl solution during 30 min) and an environmental change
      (transfer from a 2 m(3) fibreglass square tank to 50 L aquaria) were used as
      acute stressors and compared to a single cortisol injection (0.5 or 5 mg kg(-1)
      body weight). For both acute stress and cortisol injection (0.5 mg kg(-1) body
      weight), serum cortisol level was significantly increased from 2.3 to 134.1 ng
      mL(-1) 1 h post-stress/injection and returned to a resting basal value 24 h after
      the stress/injection. In fish injected with 5 mg kg(-1) body weight cortisol,
      mean serum cortisol level reached a peak up to 2500 ng mL(-1) 1 h after
      injection. 63 % of the females (mean body weight: 242 +/- 4 g) submitted to the
      acute stress ovulated within 72 h after the stress. In the same way, cortisol
      injection (5 mg kg(-1) body weight) at the 10th day of the maturation cycle led
      to a twofold reduction of the time before ovulation compared to vehicle injected
      control fish. Relative and total fecundity were significantly decreased in
      females submitted to an acute stress or cortisol injected at 5 mg kg(-1) body
      weight, but not fertilization or hatching rates. In conclusion, acute stress and
      cortisol induction exert both positive and negative effects on the final
      reproductive process in O. niloticus, and cortisol is the endocrine mediator
      causing these changes.

PMID- 22610262
TI  - Deproto-metallation and computed CH acidity of 2-aryl-1,2,3-triazoles.
AB  - 2-Aryl-1,2,3-triazoles were synthesized by cyclization of the corresponding
      glyoxal arylosazones, generated from commercial arylhydrazines. The deproto
      metallation of 2-phenyl-1,2,3-triazole was attempted using different 2,2,6,6
      tetramethylpiperidino-based mixed lithium-metal (Zn, Cd, Cu, Co, Fe)
      combinations, giving results in the case of Zn, Cd, and Cu. The lithium-zinc
      combination was next selected to apply the deprotonation-iodination sequence to
      all the 2-aryl-1,2,3-triazoles synthesized. The results were analyzed with the
      help of the CH acidities of the substrates, determined in THF solution using the
      DFT B3LYP method.

PMID- 22610264
TI  - Treatment of common bile duct stones in Sweden 1989-2006: an observational
      nationwide study of a paradigm shift.
AB  - BACKGROUND: The preferred strategies for treatment of common bile duct stones
      have changed from choledochotomy with cholecystectomy to sphincterotomy with or
      without cholecystectomy. The aim of the present study was to compare the
      effectiveness of these treatment strategies on a nationwide level in Sweden.
      METHODS: All patients with hospital care for benign biliary diagnoses 1988-2006
      were identified in Swedish registers. Patients with common bile duct stones and a
      first admission with choledochotomy and or endoscopic sphincterotomy from 1989
      through 2006 comprised the study group. These patients were analyzed with respect
      to readmission for biliary diagnoses and acute pancreatitis. RESULTS: Incidence
      of open and laparoscopic choledochotomy decreased from 19.4 to 5.2, whereas
      endoscopic sphincterotomy increased from 5.1 to 26.1 per 100,000 inhabitants per
      year, respectively. Among patients treated for common bile duct stones (n =
      26,815), 60.0 % underwent cholecystectomy during the first hospital admission in
      1989-1994, compared to 30.1 % in 2001-2006. The treatment strategy that included
      endoscopic sphincterotomy was associated with more readmissions for biliary
      diagnoses and increased risk for acute pancreatitis than the treatment strategy
      with choledochotomy. However, patients treated with endoscopic sphincterotomy and
      concurrent cholecystectomy at the index admission had the lowest risk of
      readmission. CONCLUSIONS: Cholecystectomy has been increasingly separated from
      treatment of bile duct stones, and endoscopic sphincterotomy has superseded
      choledochotomy as a first alternative for bile duct clearance in Sweden. In
      patients fit for surgery, clearance of the common bile duct can be combined with
      cholecystectomy, as it probably reduces the need for biliary related
      readmissions.

PMID- 22610265
TI  - Overall distribution of trauma-related deaths in Berlin 2010: advancement or
      stagnation of German trauma management?
AB  - BACKGROUND: Trauma is the leading cause of death among children, adolescents, and
      young adults. The latest data from the German Trauma Registry reveals a constant
      decrease in trauma mortality, indicating that 11.6 % of all trauma patients in
      2010 died in hospital. Notably, trauma casualties dying before admission to
      hospital have not been systematically surveyed and analyzed in Germany. METHODS:
      We conducted a prospective observational study of all traumatic deaths in Berlin,
      recording demographic data, trauma mechanisms, and causes/localization and time
      of death after trauma. Inclusion criteria were all deaths following trauma from 1
      January 2010 to 31 December 2010. RESULTS: A total of 440 trauma fatalities were
      included in this study, with a mortality rate of 13/100,000 inhabitants; 78.6 %
      were blunt injuries, and fall from a height >3 m (32.7 %) was the leading trauma
      mechanism. 32.5 % died immediately, 23.9 % died within 60 min, 7.7 % died within
      1-4 h, 16.8 % died within 4-48 h, 11.1 % died <1 week later, and 8 % died >1 week
      after trauma. The predominant causes of death were polytrauma (45.7 %), sTBI (38
      %), exsanguination (9.5 %), and thoracic trauma (3.2 %). Death occurred on-scene
      in 58.7 % of these cases, in the intensive care unit in 33.2 %, and in 2.7 % of
      the cases, in the emergency department, the operating room, and the ward,
      respectively. CONCLUSIONS: Polytrauma is the leading cause of death, followed by
      severe traumatic brain injury (sTBI). The temporal analysis of traumatic death
      indicates a shift from the classic "trimodal" distribution to a new "bimodal"
      distribution. Besides advances in road safety, prevention programs and
      improvement in trauma management-especially the pre-hospital phase-have the
      potential to significantly improve the survival rate after trauma.

PMID- 22610266
TI  - Severity of complications after gastrectomy in elderly patients with gastric
      cancer.
AB  - BACKGROUND: The risk of surgery for gastric cancer has not been fully evaluated,
      and this study aimed to assess the severity of postoperative complications after
      D2 or modified D2 gastrectomy in elderly patients. METHODS: Eligible patients
      were retrospectively selected from the Kanagawa Cancer Center database between
      1990 and 2009 based on the following criteria: age >=80 years and D2 or modified
      D2 gastrectomy as a primary treatment for gastric cancer. The severity of
      complications was evaluated using the Clavien-Dindo classification. RESULTS: A
      total of 83 patients with a median age of 82 years (range 80-88 years) were
      entered in this study. Sixty (72 %) had at least one co-morbid condition.
      American Society of Anesthesiologists scores were 2 in 66 patients and 3 in 17
      patients. The extent of gastrectomy was distal in 65 (78 %) and total in 18 (22
      %) patients. The procedure used for lymphadenectomy was modified D2 in 38 (46 %)
      and D2 in 45 (54 %) patients. Altogether, 18 complications were observed in 15
      patients. The overall morbidity rate was 18 % [95 % confidence interval (CI) 9.7
      26.2 %], and the mortality rate was 3.6 % (95 % CI 0-7.6 %). Complications were
      classified as grade 2 (n = 9), grade 3a (n = 1), grade 3b (n = 4), grade 4 (n =
      1), and grade 5 (n = 3). Severe complications (>= grade 3) occurred in 8.4 % (95
      % CI 2.4-14.4 %). CONCLUSIONS: The morbidity rate was acceptable, but that of
      severe complications was high, suggesting that surgery for gastric cancer in
      elderly patients is risky and should be limited.

PMID- 22610267
TI  - Prospective evaluation of a single-sided innervated gluteal artery perforator
      flap for reconstruction of extensive and recurrent pilonidal sinus disease:
      functional, aesthetic, and patient-reported long-term outcomes.

PMID- 22610268
TI  - Rationale for the prevention of syncope trial IV: assessment of midodrine.
AB  - BACKGROUND: Vasovagal syncope is a common problem associated with a poor quality
      of life, which improves when the frequency of syncope is reduced. Effective
      pharmacological therapies for vasovagal syncope have been elusive. Midodrine is a
      pro-drug whose primary metabolite is an alpha-1 adrenoreceptor agonist. A few
      studies have suggested that it may be beneficial in syncope, but all have had
      significant methodological limitations. A placebo-controlled clinical trial of
      midodrine for the prevention of vasovagal syncope is needed. STRUCTURE OF STUDY:
      The prevention of syncope trial IV (POST 4) is a multicenter, international,
      randomized, placebo-controlled study of midodrine in the prevention of vasovagal
      syncope. The primary end point is the time to first recurrence of syncope.
      Patients will be randomized 1:1 to receive midodrine 10-30 mg/day or matching
      placebo, and followed for 1 year. Secondary end points include syncope frequency,
      presyncope, and quality of life. Primary analysis will be performed with an
      intention-to-treat approach, with a secondary on-treatment analysis. POWER
      CALCULATIONS: A total sample size of 112, split equally between the two groups,
      achieves 85 % power to detect a 50 % relative risk reduction when the event rates
      are 55 and 27.5 % in the placebo and midodrine arms. Allowing for 20 % dropout,
      we propose to enroll 140 patients. REGISTRATION: POST 4 is registered with
      http://www.clinicaltrials.gov (NCT01456481). IMPLICATIONS: This study will be the
      first adequately powered trial to determine whether midodrine is effective in
      preventing vasovagal syncope. If it is effective, then midodrine may become the
      first-line pharmacological therapy for this condition.

PMID- 22610271
TI  - Differences between mainstream and sidestream tobacco smoke extracts and nicotine
      in the activation and aggregation of platelets subjected to cardiovascular
      conditions in diabetes.
AB  - Mainstream and sidestream tobacco smoke extracts have been shown to increase
      platelet activation directly. Furthermore, advanced glycation end products, which
      are present in the diabetic vasculature, have also been shown to enhance platelet
      activity. However, the combined effects of these two risk factors on platelet
      functions remain unclear. Platelets were exposed to tobacco extracts concurrently
      with advanced glycation end products. Timed samples were removed to assess the
      extent of platelet activity. The presence of smoke extracts enhanced platelet
      activity as compared to control conditions, this was especially prevalent for
      sidestream extracts. With the addition of irreversibly glycated albumin, there
      was an additive effect, further enhancing platelet responses. This was at least
      partially regulated by alpha-granule release and CD41 expression. The combination
      of cardiovascular risk factors can significantly enhance platelet activation and
      aggregation, and therefore it is possible to accelerate cardiovascular diseases
      through the interactions of multiple cardiovascular risk factors.

PMID- 22610269
TI  - The impact of chemotherapy-related nausea on patients' nutritional status,
      psychological distress and quality of life.
AB  - PURPOSE: Nausea is a troublesome and distressing symptom for patients receiving
      chemotherapy. While vomiting is well controlled with current antiemetics, nausea
      is a more difficult symptom to manage. The aim of this study was to assess the
      impact of nausea on nutritional status, quality of life and psychological
      distress. METHODS: This was a prospective observational study over two cycles of
      chemotherapy. Patients completed the Multinational Association of Supportive Care
      in Cancer Antiemesis Tool, a measure of nutritional status (Patient-Generated
      Subjective Global Assessment), the Functional Assessment of Cancer Therapy
      General (FACT-G) quality of life scale and the Hospital Anxiety and Depression
      Scale at the end of each chemotherapy cycle (around day 10 post-chemotherapy).
      RESULTS: The sample consisted of 104 patients, primarily female, receiving
      anthracycline-based chemotherapy. While vomiting was minimal (5.2-14.6 % of the
      patients), high levels of nausea were observed (55.2-72.9 %), and severe nausea
      (>6 on a 0-10 scale) was reported by 20.5-29.2 % of the participants. Severe
      nausea had a borderline significant impact in relation to physical functioning (p
      = 0.025) and a significant impact on nutritional status (severe acute nausea, p =
      0.003; severe delayed nausea, p = 0.017). Clinically meaningful changes were
      observed in relation to the FACT-G total score. CONCLUSION: Chemotherapy-induced
      nausea does have an impact on nutritional status and physical functioning and can
      impair anxiety and quality of life. As a key symptom associated with other
      symptoms, it is imperative that greater attention is given to managing treatment
      related nausea through innovative non-pharmacological and nutritional
      interventions.

PMID- 22610272
TI  - Hydranencephaly, pituitary hypoplasia, and anophthalmia in a male infant.

PMID- 22610270
TI  - Structural basis for modification of flavonol and naphthol glucoconjugates by
      Nicotiana tabacum malonyltransferase (NtMaT1).
AB  - Plant HXXXD acyltransferase-catalyzed malonylation is an important modification
      reaction in elaborating the structural diversity of flavonoids and anthocyanins,
      and a universal adaptive mechanism to detoxify xenobiotics. Nicotiana tabacum
      malonyltransferase 1 (NtMaT1) is a member of anthocyanin acyltransferase
      subfamily that uses malonyl-CoA (MLC) as donor catalyzing transacylation in a
      range of flavonoid and naphthol glucosides. To gain insights into the molecular
      basis underlying its catalytic mechanism and versatile substrate specificity, we
      resolved the X-ray crystal structure of NtMaT1 to 3.1 A resolution. The structure
      comprises two alpha/beta mixed subdomains, as typically found in the HXXXD
      acyltransferases. The partial electron density map of malonyl-CoA allowed us to
      reliably dock the entire molecule into the solvent channel and subsequently
      define the binding sites for both donor and acceptor substrates. MLC bound to the
      NtMaT1 occupies one end of the long solvent channel between two subdomains. On
      superimposing and comparing the structure of NtMaT1 with that of an enzyme from
      anthocyanin acyltransferase subfamily from red chrysanthemum (Dm3Mat3) revealed
      large architectural variation in the binding sites, both for the acyl donor and
      for the acceptor, although their overall protein folds are structurally
      conserved. Consequently, the shape and the interactions of malonyl-CoA with the
      binding sites' amino acid residues differ substantially. These major local
      architectural disparities point to the independent, divergent evolution of plant
      HXXXD acyltransferases in different species. The structural flexibility of the
      enzyme and the amendable binding pattern of the substrates provide a basis for
      the evolution of the distinct, versatile substrate specificity of plant HXXXD
      acyltransferases.

PMID- 22610273
TI  - Hypertelorism, radial ray defects, dextrocardia, hypoplastic ribs and renal
      anomaly:  report of a second case and confirmation of the phenotype.

PMID- 22610274
TI  - Outcome of sentinel lymph node biopsy and prognostic implications of regression
      in thin malignant melanoma.
AB  - Thin melanomas with partial or complete regression may provide clues about
      antitumor immunity, but their management remains controversial. We have
      characterized the management and clinical outcomes of regressed thin (<1 mm) T1a
      melanomas and hypothesized that regression increases the risk of regional
      metastases when compared with nonregressed thin melanomas. A prospectively
      collected clinical database was reviewed, and T1a melanomas with regression were
      identified. Histology, surgical approach, outcome, and survival were evaluated.
      The primary outcome measures were sentinel node positivity, subsequent lymph node
      metastasis, and survival. A total of 75 patients with T1a or in-situ melanomas
      were grouped into three subsets. Group 1: 35 underwent a sentinel node biopsy
      (SNBx), none of which were positive. No patients developed nodal recurrence. The
      5-year survival of this group was 93%, with a median follow-up of 52 months.
      Group 2: 31 were followed up without SNBx; two developed regional nodal disease
      (6.5%), neither of whom died of subsequent distant disease. The 5-year survival
      was 89%, with a median follow-up of 38 months. There was no significant
      difference in the survival between groups 1 and 2. Group 3: nine patients
      presented with metastatic disease concurrent with a regressed thin melanoma.
      These patients had a median survival of 2.3 years and a 4-year survival estimate
      of 22%. Regression should not be used as an indication for SNBx in T1a melanomas;
      we recommend that such patients be managed with wide local excision and a long
      term clinical follow-up. The poor prognosis of thin regressed primary melanoma
      with simultaneous metastatic disease may indicate the existence of immune escape
      phenotypes supporting melanoma progression.

PMID- 22610275
TI  - The multifaceted balance of TNF-alpha and type I/II interferon responses in SLE
      and RA: how monocytes manage the impact of cytokines.
AB  - Many cytokines are involved in the pathogenesis of autoimmune diseases and are
      recognized as relevant therapeutic targets to attenuate inflammation, such as
      tumor necrosis factor (TNF)-alpha in rheumatoid arthritis (RA) and interferon
      (IFN)-alpha/gamma in systemic lupus erythematosus (SLE). To relate the
      transcriptional imprinting of cytokines in a cell type- and disease-specific
      manner, we generated gene expression profiles from peripheral monocytes of SLE
      and RA patients and compared them to in vitro-generated signatures induced by TNF
      alpha, IFN-alpha2a, and IFN-gamma. Monocytes from SLE and RA patients revealed
      disease-specific gene expression profiles. In vitro-generated signatures induced
      by IFN-alpha2a and IFN-gamma showed similar profiles that only partially
      overlapped with those induced by TNF-alpha. Comparisons between disease-specific
      and in vitro-generated signatures identified cytokine-regulated genes in SLE and
      RA with qualitative and quantitative differences. The IFN responses in SLE and RA
      were found to be regulated in a STAT1-dependent and STAT1-independent manner,
      respectively. Similarly, genes recognized as TNF-alpha regulated were clearly
      distinguishable between RA and SLE patients. While the activity of SLE monocytes
      was mainly driven by IFN, the activity from RA monocytes showed a dominance of
      TNF-alpha that was characterized by STAT1 down-regulation. The responses to
      specific cytokines were revealed to be disease-dependent and reflected the
      interplay of cytokines within various inflammatory milieus. This study has
      demonstrated that monocytes from RA and SLE patients exhibit disease-specific
      gene expression profiles, which can be molecularly dissected when compared with
      in vitro-generated cytokine signatures. The results suggest that an assessment of
      cytokine-response status in monocytes may be helpful for improvement of diagnosis
      and selection of the best cytokine target for therapeutic intervention.

PMID- 22610276
TI  - A novel COCH mutation associated with autosomal dominant nonsyndromic hearing
      loss disrupts the structural stability of the vWFA2 domain.
AB  - Mutations in COCH have been associated with autosomal dominant nonsyndromic
      hearing loss (DFNA9) and are frequently accompanied by vestibular hypofunction.
      Here, we report identification of a novel missense mutation, p.F527C, located in
      the vWFA2 domain in members of a Korean family with late-onset and progressive
      hearing loss. To assess the molecular characteristics of this cochlin mutant, we
      constructed both wild-type and mutant cochlin constructs and transfected these
      into mammalian cell lines. Results of immunocytochemistry analysis demonstrated
      localization of the cochlin mutant in the endoplasmic reticulum/Golgi complex,
      whereas western blot analyses of cell lysates revealed that the mutant cochlin
      tends to form covalent complexes that are retained in the cell. Biochemical
      analyses of recombinant vWFA2 domain of cochlin carrying the p.F527C mutation
      revealed that the mutation increases propensity of the protein to form covalent
      disulfide-bonded dimers and affects the structural stability but not the collagen
      affinity of the vWFA2 domain. We suggest that the instability of mutant cochlin
      is the major driving force for cochlin aggregation in the inner ear in DFNA9
      patients carrying the COCH p.F527C mutation.

PMID- 22610277
TI  - beta-catenin confers resistance to PI3K and AKT inhibitors and subverts FOXO3a to
      promote metastasis in colon cancer.
AB  - The Wnt-beta-catenin and PI3K-AKT-FOXO3a pathways have a central role in cancer.
      AKT phosporylates FOXO3a, relocating it from the cell nucleus to the cytoplasm,
      an effect that is reversed by PI3K and AKT inhibitors. Simultaneous
      hyperactivation of the Wnt-beta-catenin pathway and inhibition of PI3K-AKT
      signaling promote nuclear accumulation of beta-catenin and FOXO3a, respectively,
      promoting cell scattering and metastasis by regulating a defined set of target
      genes. Indeed, the anti-tumoral AKT inhibitor API-2 promotes nuclear FOXO3a
      accumulation and metastasis of cells with high nuclear beta-catenin content.
      Nuclear beta-catenin confers resistance to the FOXO3a-mediated apoptosis induced
      by PI3K and AKT inhibitors in patient-derived primary cultures and in
      corresponding xenograft tumors in mice. This resistance is reversed by XAV-939,
      an inhibitor of Wnt-beta-catenin signaling. In the presence of high nuclear beta
      catenin content, activation of FOXO3a by PI3K or AKT inhibitors makes it behave
      as a metastasis inductor rather than a proapoptotic tumor suppressor. We show
      that it is possible to evaluate the beta-catenin status of patients' carcinomas
      and the response of patient-derived cells to target-directed drugs that
      accumulate FOXO3a in the nucleus before deciding on a course of treatment. We
      propose that this evaluation could be essential to the provision of a safer and
      more effective personalized treatment.

PMID- 22610278
TI  - A high-throughput drug screen for Entamoeba histolytica identifies a new lead and
      target.
AB  - Entamoeba histolytica, a protozoan intestinal parasite, is the causative agent of
      human amebiasis. Amebiasis is the fourth leading cause of death and the third
      leading cause of morbidity due to protozoan infections worldwide(1), resulting in
      ~70,000 deaths annually. E. histolytica has been listed by the National
      Institutes of Health as a category B priority biodefense pathogen in the United
      States. Treatment relies on metronidazole(2), which has adverse effects(3), and
      potential resistance of E. histolytica to the drug is an increasing concern(4,5).
      To facilitate drug screening for this anaerobic protozoan, we developed and
      validated an automated, high-throughput screen (HTS). This screen identified
      auranofin, a US Food and Drug Administration (FDA)-approved drug used
      therapeutically for rheumatoid arthritis, as active against E. histolytica in
      culture. Auranofin was ten times more potent against E. histolytica than
      metronidazole. Transcriptional profiling and thioredoxin reductase assays
      suggested that auranofin targets the E. histolytica thioredoxin reductase,
      preventing the reduction of thioredoxin and enhancing sensitivity of trophozoites
      to reactive oxygen-mediated killing. In a mouse model of amebic colitis and a
      hamster model of amebic liver abscess, oral auranofin markedly decreased the
      number of parasites, the detrimental host inflammatory response and hepatic
      damage. This new use of auranofin represents a promising therapy for amebiasis,
      and the drug has been granted orphan-drug status from the FDA.

PMID- 22610279
TI  - Jejunal nutrient sensing is required for duodenal-jejunal bypass surgery to
      rapidly lower glucose concentrations in uncontrolled diabetes.
AB  - Gastrointestinal bypass surgeries restore metabolic homeostasis in patients with
      type 2 diabetes and obesity(1), but the underlying mechanisms remain elusive.
      Duodenal-jejunal bypass surgery (DJB), an experimental surgical technique that
      excludes the duodenum and proximal jejunum from nutrient transit(1,2), lowers
      glucose concentrations in nonobese type 2 diabetic rats(2-5). Given that DJB
      redirects and enhances nutrient flow into the jejunum and that jejunal nutrient
      sensing affects feeding(6,7), the repositioned jejunum after DJB represents a
      junction at which nutrients could regulate glucose homeostasis. Here we found
      that intrajejunal nutrient administration lowered endogenous glucose production
      in normal rats through a gut-brain-liver network in the presence of basal plasma
      insulin concentrations. Inhibition of jejunal glucose uptake or formation of long
      chain fatty acyl-coA negated the metabolic effects of glucose or lipid,
      respectively, in normal rats, and altered the rapid (2 d) glucose-lowering effect
      induced by DJB in streptozotocin (STZ)-induced uncontrolled diabetic rats during
      refeeding. Lastly, in insulin-deficient autoimmune type 1 diabetic rats and STZ
      induced diabetic rats, DJB lowered glucose concentrations in 2 d independently of
      changes in plasma insulin concentrations, food intake and body weight. These data
      unveil a glucoregulatory role of jejunal nutrient sensing and its relevance in
      the early improvement of glycemic control after DJB in rat models of uncontrolled
      diabetes.

PMID- 22610281
TI  - A tris(2-quinolylmethyl)amine scaffold that promotes hydrogen bonding within the
      secondary coordination sphere.
AB  - A new quinolyl-based ligand presents three amide functionalities to act as
      hydrogen-bond accepting groups to a metal-bound substrate at a well-defined
      distance. As a confirmation of the design strategy, CH(3)CN coordinated to
      copper(II) participates in CH-O interactions in the solid state and in solution.

PMID- 22610280
TI  - Peroxiredoxin family proteins are key initiators of post-ischemic inflammation in
      the brain.
AB  - Post-ischemic inflammation is an essential step in the progression of brain
      ischemia-reperfusion injury. However, the mechanism that activates infiltrating
      macrophages in the ischemic brain remains to be clarified. Here we demonstrate
      that peroxiredoxin (Prx) family proteins released extracellularly from necrotic
      brain cells induce expression of inflammatory cytokines including interleukin-23
      in macrophages through activation of Toll-like receptor 2 (TLR2) and TLR4,
      thereby promoting neural cell death, even though intracellular Prxs have been
      shown to be neuroprotective. The extracellular release of Prxs in the ischemic
      core occurred 12 h after stroke onset, and neutralization of extracellular Prxs
      with antibodies suppressed inflammatory cytokine expression and infarct volume
      growth. In contrast, high mobility group box 1 (HMGB1), a well-known damage
      associated molecular pattern molecule, was released before Prx and had a limited
      role in post-ischemic macrophage activation. We thus propose that extracellular
      Prxs are previously unknown danger signals in the ischemic brain and that its
      blocking agents are potent neuroprotective tools.

PMID- 22610282
TI  - A sensitive electrochemical biosensor for detection of DNA methyltransferase
      activity by combining DNA methylation-sensitive cleavage and terminal transferase
      mediated extension.
AB  - A novel electrochemical biosensor was developed for activity assay of DNA
      methyltransferase and its inhibitor based on methylation-sensitive cleavage,
      which activated a primer for terminal transferase-mediated extension of
      biotinylated dUTP followed by sensitive detection via enzymatic amplification.

PMID- 22610284
TI  - Disease caused by non-tuberculous mycobacteria: diagnostic procedures and
      treatment evaluation in the North of Buenos Aires Province.
AB  - Non-tuberculous mycobacteria (NTM) have emerged as pathogens frequently
      associated to HIV co-infection. The aims of this study were to describe the
      clinical importance of NTM in patients from the North of Buenos Aires Province
      and the drug-susceptibility patterns in relation with the therapy used. A total
      of 23,624 clinical specimens were investigated during the period 2004-2010. Ziehl
      Neelsen stain and cultures were used for diagnosis. Molecular and biochemical
      tests were performed to identify the mycobacteria. TB and mycobacterioses cases
      were 2 118 and 108 respectively. Sixteen NTM species were found: Mycobacterium
      avium and Mycobacterium intracellulare as the main causative agents. Infections
      produced by more than one species at the same time were confirmed (4 cases).
      Macrolides and fluoroquinolones were the most active in vitro drugs. Treatment
      evaluation showed that 68.0 % of the cases completed the therapy, 20 % died; and
      12 % were relapses. The cases in which the treatment outcome was evaluated
      received an individual tailor-made therapeutic scheme including those drugs
      showing in vitro activity and presumed in vivo usefulness. More than a quarter of
      the patients had HIV co-infection and the majority of the deaths were associated
      with this co-infection.

PMID- 22610283
TI  - Impact of excipient interactions on drug bioavailability from solid dosage forms.
AB  - Excipients are generally pharmacologically inert, but can interact with drugs in
      the dosage form and the physiological factors at the site of absorption to affect
      the bioavailability of a drug product. A general mechanistic understanding of the
      basis of these interactions is essential to design robust drug products. This
      paper focuses on drug-excipient interactions in solid dosage forms that impact
      drug bioavailability, the drug substance and drug product properties affected by
      excipients, and the impact of excipients on physiologic processes. The extent to
      which drug bioavailability is affected by these interactions would vary on a case
      by-case basis depending upon factors such as the potency and dose of the drug,
      therapeutic window, site of absorption, rate limiting factor in drug absorption
      (e.g., permeability or solubility limited), or whether drug metabolism, efflux,
      complexation, or degradation at the site of absorption play a role in determining
      its bioavailability. Nonetheless, a mechanistic understanding of drug-excipient
      interactions and their impact on drug release and absorption can help develop
      formulations that exhibit optimum drug bioavailability.

PMID- 22610286
TI  - Penicillium species present in Uruguayan salami.
AB  - The surface coverage of certain dry fermented sausages such as Italian salami by
      some species of Penicillium provides their characteristic flavor and other
      beneficial properties. One of them is the protective effect by means of a uniform
      film of white mold against undesirable microorganisms. The aim of this work was
      to identify and to isolate the fungal species present in mature Italian type of
      salami and to evaluate if it is possible to obtain some of them as starters. In
      addition, the effects of temperature (14  degrees C and 25  degrees C), water
      activity (a w) (0.90, 0.95 and 0.995) and 2.5 % sodium chloride (NaCl) on fungal
      growth were determined. Similarly, the proteolytic and lipolytic activity and the
      ability to produce toxic secondary metabolites were evaluated in order to
      characterize some possible starter strain. All species found belong to the genus
      Penicillium, including a performing starter as Penicillium nalgiovense and some
      potentially toxicogenic species. All the strains showed a higher growth rate at
      25  degrees C. The production of extracellular proteases and lipases was
      significantly higher at 25  degrees C than at 14  degrees C with and without
      sodium chloride. Only Penicillium expansum produced patulin. On the other hand,
      Penicillium griseofulvum was the only species that produced ciclopiazonic acid
      but none of the strains produced penicillin. The species present on salami,
      Penicillium nalgiovense, Penicillium minioluteum, Penicillium brevicompactum and
      Penicillium puberulum were unable to produce any of the evaluated toxins. These
      findings suggest that some fungal isolates from the surface of salami such as P.
      nalgiovense are potentially useful as starters in sausage manufacture.

PMID- 22610287
TI  - Selective grazing by protists upon enteric bacteria in an aquatic system.
AB  - It is well known that protozoan grazing can be an important agent of mortality
      for suspended bacteria, both in marine and freshwater environments. Considering
      that the presence of fecal contamination is a frequent phenomenon in triese
      environments, and that Escherichia coli and the genus Enterococcus are indicators
      of microbiological water quality, the effect of protozoan grazing on E. coli and
      Enterococcus faecalis in Los Padres Lagoon waters (Buenos Aires, Argentina, 37
      degrees  56'30" S, 57 degrees  44'30" W) was herein analyzed. Microcosm assays
      were carried out, simulating lacustrine conditions, confronting suspensions of
      autochthonous bacterivorous protozoans with suspensions of autochthonous and
      collection strains of E. coli and E. faecalis, combined and individually. Daily
      counts were made for evaluating bacterial survival and the number of ciliates.
      The results obtained indicate that there is a preferential sequence for bacterial
      removal in the water, where E. faecalis is more grazing-resistant than E. coli.
      Moreover, it was noted that the origin of bacterial strains influenced their
      sensitivity for grazing, at least in the short term (e.g. the collection strains
      were less affected). We conclude that protozoan grazing can modify the relative
      abundance of fecal indicator microorganisms, thus altering the results of water
      quality studies.

PMID- 22610285
TI  - [Resistance to extended-spectrum cephalosporins in non-inducible AmpC
      enterobacteria: evaluation of the new MIC breakpoints].
AB  - The aims of this study were to evaluate the in vitro activity of extended
      spectrum cephalosporins (ESC) in non-inducible AmpC enterobacteria through
      phenotypic and genotypic characterization of the mechanisms of resistance (ESBL,
      plasmid-mediated AmpC and KPC) and to evaluate the interpretation criteria
      proposed by the existing recommendations and the new breakpoints established by
      the CLSI and the EUCAST. Susceptibility tests and PCR multiplex for b/aSHV and
      b/aCTX-M and amplification using specific primers was performed. One hundred
      sixty nine resistant isolates: K/ebsie//a pneumoniae (95), Escherichia co/i (55),
      and Proteus mirabi/is (19) were recovered. ESC resistance was 56.2 %, 32.6%, and
      11.2 %, respectively. ESBL was detected in 152 (90 %) isolates, plasmid-mediated
      AmpC in 12 (7 %) and KPC in 5 (3 %). The CLSI 2009 recommendations and the
      breakpoints suggested by the CLSI 2010 and the EUCAST for ceftriaxone were
      efficacious to detect ESBL, whereas the different breakpoints for ceftazidime
      presented discrepancies. The CLSI 2010 breakpoints only detected 55 % of the ESBL
      producing isolates due to the endemic presence of CTX-M ESBLs in our country.
      Regarding the plasmid-mediated AmpC producers, the recommendations of the CLSI
      2010 and the EUCAST 2010 proved to be more efficient than the old ones.

PMID- 22610288
TI  - Bioprospection of marine microorganisms: biotechnological applications and
      methods.
AB  - Environmental microorganisms constitute an almost inexhaustible reserve of
      genetic and functional diversity, accumulated during millions of years of
      adaptive evolution to various selective pressures. In particular, the extent of
      microbial biodiversity in marine habitats seems to grow larger as new techniques
      emerge to measure it. This has resulted in novel and more complex approaches for
      the screening of molecules and activities of biotechnological interest in these
      environments. In this review, we explore the different partially overlapping
      biotechnological fields that make use of microorganisms and we describe the
      different marine habitats that are particularly attractive for bioprospection. In
      addition, we review the methodological approaches currently used for microbial
      bioprospection, from the traditional cultivation techniques to state of the art
      metagenomic approaches, with emphasis in the marine environment.

PMID- 22610290
TI  - [Salvador Mazza: a rebel with a cause].

PMID- 22610289
TI  - [Vesiculobullous lesions in an immunocompromised cancer patient].

PMID- 22610291
TI  - [Community-acquired bacteremia in adult patients attending the emergency service
      of a teaching hospital].
AB  - Bacteremia is an important cause of morbimortality. This study describes the
      episodes of community-acquired bacteremia in adult patients registered at our
      hospital. Between January 2005, and December 2009, 271 episodes were studied. The
      diagnostic yield of blood cultures was 13.5 %. A total of 52 % of patients were
      male and 48 % female. The mean age was 60. The most frequent comorbidities were:
      diabetes (21 %), neoplasia (18 %), cardiopathy (11 %), and HIV infection (8 %).
      The focus was- respiratory (21 %), urinary (15 %), cutaneous (9 %), and others
      (13 %). Gram-positive bacteria prevailed (51.4%). The most frequent
      microorganisms were Escherichia coli (25 %), Streptococcus pneumoniae (22.9 %),
      and Staphylococcus aureus (12.3 %). Bacteremia was polymicrobial in 7 % of the
      cases. Thirty three percent of E. coli isolates were resistant to ciprofloxacin
      and 6 % to ceftazidime. Fourteen percent of S. aureus strains were resistant to
      oxacillin whereas only 7 % of S. pneumoniae expressed high resistance to
      penicillin with MICs = 2 ug/ml, according to meningitis breakpoints.

PMID- 22610292
TI  - In vitro oxidant effects of D-glucosamine reduce adhesion and biofilm formation
      of Staphylococcus epidermidis.
AB  - Staphylococcus epidermidis is a common pathogen in medical device-associated
      infections. Its major pathogenic factor is the ability to form adherent biofilms.
      In this work, three S. epidermidis strains isolated from infected catheters were
      chosen with the objective of investigating the effect of D-glucosamine (D-Glu) on
      reactive oxygen species (ROS) production, adhesion and biofilm formation. The
      chemiluminescence and nitroblue tetrazolium reduction assays were used to
      determine ROS production by planktonic S. epidermidis and the microtiter plate
      assay to quantify in vitro biofilm formation. D-Glu generated a dose-dependent
      increase in ROS in planktonic cells with maximum stimuli at a concentration of
      0.05 mM, and reduced adhesion and biofilm formation. On the other hand, glucose
      showed an antioxidative stress action and promoted biofilm adhesion and growth.
      This study suggests a potential application of D-Glu against infections
      associated with indwelling medical devices, since the oxidative stress caused by
      this hexosamine in planktonic S. epidermidis contributed to reducing biofilm
      formation.

PMID- 22610293
TI  - [Onychomycoses: epidemiology, causative agents and assessment of diagnostic
      laboratory methods].
AB  - Since March 2007 to March 2011, 414 patients with onychopathies were
      prospectively analyzed. Prevalence of the toenail and fingernail mycoses was 78 %
      and 58 %, respectively. The major etiological agents were Trichophyton rubrum,
      Candida spp. and Trichophyton mentagrophytes. Dermatophytes were more frequently
      cultured from toenails, whereas Candida spp. from fingernails (both, p < 0.05).
      In candidal onychomycosis, species different from C. albicans were prevalent. A
      higher prevalence of toenail and fingernail mycoses, a predominance of T. rubrum
      in toenails (p < 0.05), and greater positivity in the direct examination (DE) and
      in culture (both, p < 0.05) were more frequently observed in men than in women.
      The correlation between DE and culture was 68 %. DE and culture yields were
      associated with a greater size lesion. DE was more effective in onycodystrophies
      with duration of more than 5 years. Culture positivity was independent of nail
      affection chronicity.

PMID- 22610295
TI  - Plastics in the marine environment: the dark side of a modern gift.
AB  - Plastics are cheap, strong, and durable and offer considerable benefits to
      humanity. They potentially can enhance the benefits that both medical and
      scientific technology will bestow to humankind. However, it has now been several
      decades since the use of plastics exploded, and we have evidence that our current
      approach to production, use, transport and disposal of plastic materials has
      caused, and is still causing serious effects on wildlife, and is not sustainable.
      Because of frequent inappropriate waste management practices, or irresponsible
      human behavior, large masses of plastic items have been released into the
      environment, and thereby have entered the world's oceans. Moreover, this process
      continues, and in some places is even increasing. Most plastic debris that now
      exists in the marine environment originated from ocean-based sources such as the
      fishing industry. Plastics accumulate in coastal areas, at the ocean surface and
      on the seabed. Because 70% of all plastics are known to eventually sink, it is
      suspected that ever increasing amounts of plastic items are accumulating in
      seabed sediments. Plastics do not biodegrade, although, under the influence of
      solar UV radiations, plastics do degrade and fragment into small particles,
      termed microplastics. Our oceans eventually serve as a sink for these small
      plastic particles and in one estimate, it is thought that 200,000 microplastics
      per km(2) of the ocean's surface commonly exist. The impact of plastic debris has
      been studied since the beginning of the 1960's. To date, more than 267 species in
      the marine environment are known to have been affected by plastic entanglement or
      ingestion. Marine mammals are among those species that are most affected by
      entanglement in plastic debris. By contrast, marine birds suffer the most from
      ingestion of plastics. Organisms can also be seriously absorbed by floating
      plastic debris, or the contaminants may derive from plastic additives that are
      leached to the environment. Recent studies emphasize the important role of
      microplastics as they are easily ingestible by small organisms, such as plankton
      species, and form a pathway for contaminants to enter the food web. Contaminants
      leached from plastics tend to bioaccumulate in those organisms that absorb them,
      and chemical concentrations are often higher at higher trophic levels. This
      causes a threat to the basis of every food web and can have serious and far
      reaching effects, even on nonmarine species such as polar bears and humans, who
      consume marine-grown food. Therefore, resolving the plastic debris problem is
      important to human kind for two reasons: we are both creator, and victim of the
      plastic pollution problem. Solutions to the plastic debris problem can only be
      achieved through a combination of actions. Such actions include the following:
      Legislation against marine pollution by plastics must be enforced, recycling must
      be accentuated, alternatives (biodegradable) to current plastic products must be
      found, and clean-up of debris must proceed, if the marine plastic pollution
      problem is to eventually be resolved. Governments cannot accomplish this task on
      their own, and will need help and initiative from the public. Moreover, resolving
      this long-standing problem will require time, money, and energy from many
      individuals now living and those of future generations, if a safer and cleaner
      marine environment is to be achieved.

PMID- 22610294
TI  - Performance of a commercial assay for the diagnosis of influenza A (H1N1)
      infection in comparison to the Centers for Disease Control and Prevention
      protocol of real time RT-PCR.
AB  - At the time of influenza A (H1N1) emergency, the WHO responded with remarkable
      speed by releasing guidelines and a protocol for a real-time RT-PCR assay (rRT
      PCR). The aim of the present study was to evaluate the performance of the "Real
      Time Ready Influenza A/H1N1 Detection Set" (June 2009)-Roche kit in comparison to
      the CDC reference rRT-PCR protocol. The overall sensitivity of the Roche assay
      for detection of the Inf A gene in the presence or absence of the H1 gene was
      74.5 %. The sensitivity for detecting samples that were only positive for the Inf
      A gene (absence of the H1 gene) was 53.3 % whereas the sensitivity for H1N1
      positive samples (presence of the Inf A gene and any other swine gene) was 76.4
      %. The specificity of the assay was 97.1 %. A new version of the kit (November
      2009) is now available, and a recent evaluation of its performance showed good
      sensitivity to detect pandemic H1N1 compared to other molecular assays.

PMID- 22610296
TI  - Mercury pollution in Malaysia.
AB  - Although several studies have been published on levels of mercury contamination
      of the environment, and of food and human tissues in Peninsular Malaysia, there
      is a serious dearth of research that has been performed in East Malaysia (Sabah
      and Sarawak). Industry is rapidly developing in East Malaysia, and, hence, there
      is a need for establishing baseline levels of mercury contamination in
      environmental media in that part of the country by performing monitoring studies.
      Residues of total mercury and inorganic in food samples have been determined in
      nearly all previous studies that have been conducted; however, few researchers
      have analyzed samples for the presence of methlymercury residues. Because
      methylmercury is the most toxic form of mercury, and because there is a growing
      public awareness of the risk posed by methylmercury exposure that is associated
      with fish and seafood consumption, further monitoring studies on methylmercury in
      food are also essential. From the results of previous studies, it is obvious that
      the economic development in Malaysia, in recent years, has affected the aquatic
      environment of the country. Primary areas of environmental concern are centered
      on the rivers of the west Peninsular Malaysian coast, and the coastal waters of
      the Straits of Malacca, wherein industrial activities are rapidly expanding. The
      sources of existing mercury input to both of these areas of Malaysia should be
      studied and identified. Considering the high levels of mercury that now exists in
      human tissues, efforts should be continued, and accelerated in the future, if
      possible, to monitor mercury contamination levels in the coastal states, and
      particularly along the west Peninsular Malaysian coast. Most studies that have
      been carried out on mercury residues in environmental samples are dated, having
      been conducted 20-30 years ago; therefore, the need to collect much more and more
      current data is urgent. Furthermore, establishing baseline levels of mercury
      exposure to humans in Malaysia will be useful in establishing the levels at which
      detrimental effects in both humans and marine life may occur, and therefore the
      levels at which warning should be raised or limits established. In particular, we
      believe that two or three monitoring centers should be established in Peninsular
      Malaysia, and one in East Malaysia for the specific purpose of monitoring for the
      presence of hazardous environmental chemicals, and particularly monitoring for
      heavy metals such as mercury that reach food that is subject to consistent human
      consumption.

PMID- 22610297
TI  - Genotoxic and reprotoxic effects of tritium and external gamma irradiation on
      aquatic animals.
AB  - Aquatic ecosystems are chronically exposed to natural radioactivity or to
      artificial radionuclides released by human activities (e.g., nuclear medicine and
      biology,nuclear industry, military applications). Should the nuclear industry
      expand in the future, radioactive environmental releases, under normal operating
      conditions or accidental ones, are expected to increase, which raises public
      concerns about possible consequences on the environment and human health.
      Radionuclide exposures may drive macromolecule alterations, and among
      macromolecules DNA is the major target for ionizing radiations. DNA damage, if
      not correctly repaired, may induce mutations, teratogenesis, and reproductive
      effects. As such, damage at the molecular level may have consequences at the
      population level. In this review, we present an overview of the literature
      dealing with the effects of radionuclides on DNA, development, and reproduction
      of aquatic organisms. The review focuses on the main radionuclides that are
      released by nuclear power plants under normal operating conditions, gamma
      emitters and tritium. Additionally, we fitted nonlinear curves to the dose
      response data provided in the reviewed publications and manuscripts, and thus
      obtained endpoints commonly associated with ecotoxicological studies, such as the
      EDR(10). These were then used as a common metric for comparing the values and
      data published in the literature.The effects of tritium on aquatic organisms were
      reviewed for dose rates that ranged from 29 nGy/day to 29 Gy/day. Although beta
      emission from tritium decay presents a rather special risk of damage to DNA,
      genotoxicity-induced by tritium has been scarcely studied. Most of the effects
      studied have related to reproduction and development. Species sensitivity and the
      form of tritium present are important factors that drive the ecotoxicity of
      tritium. We have concluded from this review that invertebrates are more sensitive
      to the effects of tritium than are vertebrates.Because several calculated EDR10
      values are ten times lower than background levels of gamma irradiation the
      results of some studies either markedly call into question the adequacy of the
      benchmark value of 0.24 mGy/day for aquatic ecosystems that was recommended by
      Garnier-Laplace et al. (2006), or the dose rate estimates made in the original
      research, from which our EDR(10) values were derived, were under estimated, or
      were inadequate. For gamma irradiation, the effects of several different dose
      rates on aquatic organisms were reviewed, and these ranged from 1 mGy/day to 18
      Gy/day. DNA damage from exposure to y irradiation was studied more often than for
      tritium, but the major part of the literature addressed effects on reproduction
      and development. These data sets support the benchmark value of 0.24 mGy/day,
      which is recommended to protect aquatic ecosystems. RBEs, that describe the
      relative effectiveness of different radiation types to produce the same
      biological effect, were calculated using the available datasets. These RBE values
      ranged from 0.06 to 14.9, depending on the biological effect studied, and they
      had a mean of 3.1 +/- 3.7 (standard deviation). This value is similar to the RBE
      factors of 2-3 recommended by international organizations responsible for
      providing guidance on radiation safety. Many knowledge gaps remain relative to
      the biological effects produced from exposure to tritium and y emitters. Among
      these are: Dose calculations: this review highlights several EDR(10) values that
      are below the normal range of background radiation. One explanation for this
      result is that dose rates were underestimated from uncertainties linked to the
      heterogenous distribution of tritium in cells. Therefore, the reliability of the
      concept of average dose to organisms must be addressed. Mechanisms of DNA DBS
      repair: very few studies address the most deleterious form of DNA damage, which
      are DNA DBSs. Future studies should focus on identifying impaired DNA DBS repair
      pathways and kinetics, in combination with developmental and reproductive
      effects. The transmission of genetic damage to offspring, which is of primary
      concern in the human health arena. However, there has been little work undertaken
      to assess the potential risk from germ cell mutagens in aquatic organisms,
      although this is one of the means of extrapolating effects from subcellular
      levels to populations. Reproductive behavior that is linked to alterations of
      endocrine function. Despite the importance of reproduction for population
      dynamics, many key endpoints were scarcely addressed within this topic. Hence,
      there is, to our knowledge,only one study of courtship behavior in fish exposed
      to gamma rays, while no studies of radionuclide effects on fish endocrine
      function exist. Recent technical advances in the field of endocrine disrupters
      can be used to assess the direct or indirect effects of radionuclides on
      endocrine function. Identifying whether resistance to radiation effects in the
      field result from adaptation or acclimation mechanisms. Organisms may develop
      resistance to the toxic effects of high concentrations of radionuclides.
      Adaptation occurs at the population level by genetic selection for more resistant
      organisms. To date, very few field studies exist in which adaptation has been
      addressed, despite the fact that it represents an unknown influence on observed
      biological responses.

PMID- 22610298
TI  - Elastoplasty: first experience in 12 patients.
AB  - PURPOSE: Percutaneous vertebroplasty with polymethylmethacrylate (PMMA) is used
      increasingly for pain relief in symptomatic neoplastic or osteoporotic
      compression fractures. However, restoration of the stiffness of the treated
      vertebrae might propagate secondary fracture of adjacent vertebrae. Elastoplasty
      might prevent these secondary fractures. We assessed retrospectively our
      experience with elastoplasty in 12 patients, focusing on silicone migration.
      METHODS: During the period from July 2011 to January 2012, all patients with an
      indication for vertebroplasty were treated with elastoplasty. The exclusion
      criterion was the presence of posterior wall defects. Chest computed tomography
      (CT) scans were performed to evaluate the presence of perivertebral leakage and
      pulmonary embolism. The prevalence of leakage was compared with the results
      obtained for vertebroplasty with PMMA reported in the literature. Other
      complications during the postprocedural period were recorded. RESULTS: Twenty-one
      vertebral bodies in 12 patients were treated with elastoplasty. Silicone
      pulmonary emboli were detected on the postprocedural chest CT in 60 % (6/10) of
      the patients. Leakage to the perivertebral venous plexus was seen in 67 % (14/21)
      of the treated vertebrae. One major complication occurred: severe, medication
      resistant dyspnea developed in one patient with multiple peripheral silicone
      emboli. CONCLUSIONS: This preliminary evidence suggests that VK100 silicone
      cement should not be used in elastoplasty because of the increased risk of
      silicone pulmonary embolism, when compared with the use of PMMA, which occurs
      worldwide. The major technical disadvantage is that the time taken for the VK100
      silicone material to achieve its final strength is too long for practical
      application.

PMID- 22610299
TI  - Percutaneous extraction of cement leakage after vertebroplasty under CT and
      fluoroscopy guidance: a new technique.
AB  - PURPOSE: We report a new minimally invasive technique of extraction of cement
      leakage following percutaneous vertebroplasty in adults. METHODS: Seven adult
      patients (five women, two men; mean age: 81 years) treated for vertebral
      compression fractures by percutaneous vertebroplasty had cement leakage into
      perivertebral soft tissues along the needle route. Immediately after
      vertebroplasty, the procedure of extraction was performed under computed
      tomography (CT) and fluoroscopy guidance: a Chiba needle was first inserted using
      the same route as the vertebroplasty until contact was obtained with the cement
      fragment. This needle was then used as a guide for an 11-gauge Trocar t'am
      (Thiebaud, France). After needle withdrawal, a 13-gauge endoscopy clamp was
      inserted through the cannula to extract the cement fragments. The whole procedure
      was performed under local anesthesia. RESULTS: In each patient, all cement
      fragments were withdrawn within 10 min, without complication. CONCLUSIONS: This
      report suggests that this CT- and fluoroscopy-guided percutaneous technique of
      extraction could reduce the rate of cement leakage-related complications.

PMID- 22610301
TI  - Spontaneous scapular spine fracture related to rotator cuff pathology: a report
      of two cases.
AB  - Spontaneous fractures of the scapula are rare, especially those involving the
      scapular spine. There are only a few case reports addressing this topic. Two
      cases are presented of spontaneous scapular spine fractures in patients with cuff
      tear arthropathy. Treatment was conservative, resulting in a stiff shoulder in
      both patients. The combination of oral steroids and cuff-tear arthropathy seems
      to have caused a spontaneous scapular spine fracture in these patients.
      Considering the risk of operative intervention in the elderly patient
      conservative treatment seems a reasonable alternative.

PMID- 22610302
TI  - Bilateral Galeazzi fracture-dislocations: a case report of early rehabilitation.
AB  - A 24-year-old man had bilateral Galeazzi fracture-dislocations due to a
      motorcycle accident. The right radius fracture was a simple fracture and was
      fixed with a limited contact dynamic compression plate. The left radius fracture
      was a comminuted fracture and was fixed with a long locking compression plate in
      the bridging plate fashion while maintaining reduction with a temporary external
      fixator. Postoperative computed tomography under passive rotation of both
      forearms showed acceptable congruency of the distal radioulnar joints, and early
      rehabilitation of forearm rotation was started at 2 weeks after the operation. At
      13-month follow-up, bone union of both fractures was achieved, and forearm motion
      was almost restored to normal. Moreover, no subluxation or dislocation of either
      distal radioulnar joint was observed.

PMID- 22610300
TI  - Short-term effects of Ankaferd hemostat for renal artery embolization: an
      experimental study.
AB  - PURPOSE: Renal artery embolization (RAE) is a minimally invasive therapeutic
      technique that is utilized in a number of disorders. Ankaferd is a novel
      hemostatic agent with a new mechanism of action independent of clotting factors.
      We used Ankaferd for RAE in a sheep model. METHODS: Seven adult female sheep were
      included in the study. Selective renal arteriogram using 5-F diagnostic catheter
      was performed to make sure that each kidney was fed by a single renal artery and
      the animal had normal renal vasculature. Coaxial 2.7-F microcatheter was advanced
      to the distal main renal artery. Under fluoroscopic guidance, 2 mL of Ankaferd
      mixed with 2 mL of nonionic iodinated contrast agent was slowly injected.
      Fluoroscopy was used to observe the deceleration of flow and stagnation. Control
      renal angiograms were performed just after embolization. After the procedure, the
      animals were observed for 1 day and then sacrificed with intravenous sodium
      thiopental. RESULTS: The technical success was observed in seven of the seven
      animals.. After embolization procedure, none of the animals died or experienced a
      major systemic adverse event. On macroscopic examination of the embolized
      kidneys, thrombus at the level of main renal artery formed after Ankaferd
      embolization was more compact compared with the thrombi that was not Ankaferd
      associated, which was observed elsewhere. Microscopically, majority of the renal
      tubular cells (80-90 %) were necrotic, and there was epithelial cell damage in a
      small portion of the cells (10-20 %). CONCLUSIONS: RAE was safe and effective in
      the short-term with Ankaferd in studied animals. Further studies should be
      conducted to better delineate the embolizing potential of this novel hemostatic
      agent.

PMID- 22610303
TI  - Eye movements during long-term pictorial recall.
AB  - We investigated eye movements during long-term pictorial recall. Participants
      performed a perceptual encoding task, in which they memorized 16 stimuli that
      were displayed in different areas on a computer screen. After the encoding phase
      the participants had to recall and visualize the images and answer to specific
      questions about visual details of the stimuli. One week later the participants
      repeated the pictorial recall task. Interestingly, not only in the immediate
      recall task but also 1 week later participants looked longer at the areas where
      the stimuli were encoded. The major contribution of this study is that memory for
      pictorial objects, including their spatial location, is stable and robust over
      time.

PMID- 22610308
TI  - Feasibility and short-term outcome of adjuvant FOLFOX after resection of
      colorectal liver metastases.
AB  - BACKGROUND: The role of adjuvant chemotherapy for stage IV colorectal cancer has
      so far been under-investigated. The aim of this study was to assess the
      feasibility and short-term outcome of adjuvant chemotherapy with the FOLFOX
      regimen following liver resection for patients with colorectal liver metastasis
      (CRLM). METHODS: From May 2005 to September 2010, 86 patients with CRLM underwent
      hepatic resection in the Department of Gastroenterological Surgery, Graduate
      School of Medical Sciences, Kumamoto University. Of these patients, 24 received
      FOLFOX4 or modified FOLFOX6 as postoperative adjuvant chemotherapy. RESULTS:
      Nineteen male and 5 female patients received adjuvant chemotherapy following
      liver resection. Twenty-one (87.5 %) of these patients completed 6 cycles of
      adjuvant chemotherapy. Five patients required a dose reduction due to
      neutropenia, and the dose intensities of oxaliplatin and 5-FU were 93.6 and 94.1
      %, respectively. There were no severe adverse events from the treatments. The
      median follow-up period was 48.4 months. Recurrences developed in 12 patients,
      and 3 patients died during the follow-up period. The 3- and 5-year disease-free
      survival and overall survival were 51.6 and 45.1 % and 95.5 and 76.0 %,
      respectively. CONCLUSIONS: Adjuvant FOLFOX is feasible and might provide a good
      prognosis for CRLM patients who undergo liver resection.

PMID- 22610307
TI  - Genetics and mapping of the R11 gene conferring resistance to recently emerged
      rust races, tightly linked to male fertility restoration, in sunflower
      (Helianthus annuus L.).
AB  - Sunflower oil is one of the major sources of edible oil. As the second largest
      hybrid crop in the world, hybrid sunflowers are developed by using the PET1
      cytoplasmic male sterility system that contributes to a 20 % yield advantage over
      the open-pollinated varieties. However, sunflower production in North America has
      recently been threatened by the evolution of new virulent pathotypes of sunflower
      rust caused by the fungus Puccinia helianthi Schwein. Rf ANN-1742, an 'HA 89'
      backcross restorer line derived from wild annual sunflower (Helianthus annuus
      L.), was identified as resistant to the newly emerged rust races. The aim of this
      study was to elucidate the inheritance of rust resistance and male fertility
      restoration and identify the chromosome location of the underlying genes in Rf
      ANN-1742. Chi-squared analysis of the segregation of rust response and male
      fertility in F(2) and F(3) populations revealed that both traits are controlled
      by single dominant genes, and that the rust resistance gene is closely linked to
      the restorer gene in the coupling phase. The two genes were designated as R ( 11
      ) and Rf5, respectively. A set of 723 mapped SSR markers of sunflower was used to
      screen the polymorphism between HA 89 and the resistant plant. Bulked segregant
      analysis subsequently located R ( 11 ) on linkage group (LG) 13 of sunflower.
      Based on the SSR analyses of 192 F(2) individuals, R ( 11 ) and Rf5 both mapped
      to the lower end of LG13 at a genetic distance of 1.6 cM, and shared a common
      marker, ORS728, which was mapped 1.3 cM proximal to Rf5 and 0.3 cM distal to R (
      11 ) (Rf5/ORS728/R ( 11 )). Two additional SSRs were linked to Rf5 and R ( 11 ):
      ORS995 was 4.5 cM distal to Rf5 and ORS45 was 1.0 cM proximal to R ( 11 ). The
      advantage of such an introduced alien segment harboring two genes is its large
      phenotypic effect and simple inheritance, thereby facilitating their rapid
      deployment in sunflower breeding programs. Suppressed recombination was observed
      in LGs 2, 9, and 11 as it was evident that no recombination occurred in the
      introgressed regions of LGs 2, 9, and 11 detected by 5, 9, and 22 SSR markers,
      respectively. R ( 11 ) is genetically independent from the rust R-genes R ( 1 ),
      R ( 2 ), and R ( 5 ), but may be closely linked to the rust R-gene R ( adv )
      derived from wild Helianthus argophyllus, forming a large rust R-gene cluster of
      R ( adv )/R ( 11 )/R ( 4 ) in the lower end of LG13. The relationship of Rf5 with
      Rf1 is discussed based on the marker association analysis.

PMID- 22610309
TI  - PI3Kgamma in hypertension: a novel therapeutic target controlling vascular
      myogenic tone and target organ damage.
AB  - In the past decade, several studies have characterized a number of cellular and
      molecular mechanisms that contribute to the regulation of the vascular myogenic
      response, thus affecting blood pressure regulation. Recently, phosphoinositide 3
      kinase gamma (PI3Kgamma) has been identified as a main regulator of vascular
      myogenic tone and blood pressure, a result further strengthened by a highly
      significant genome-wide association of a single nucleotide polymorphism flanking
      this gene with blood pressure regulation, in a large human population. The goal
      of this review is to summarize the available information regarding the mechanism
      whereby PI3Kgamma exerts blood pressure control, regulating myogenic tone at the
      level of L-type calcium channel in smooth muscle cells. Moreover, an overview of
      the pharmacological approaches available for targeting this signalling pathway
      shows that PI3Kgamma is a suitable candidate for antihypertensive therapy,
      capable of lowering blood pressure. Finally, a survey of the studies dissecting
      the role of PI3Kgamma in pathological conditions that are typically induced by
      hypertension in its target organs provides a more complete picture of the high
      potential of this novel therapeutic approach for fighting hypertension and, at
      the same time, its target organ damage, independently of blood pressure-lowering
      effects.

PMID- 22610311
TI  - Backbone and sidechain (1)H, (13)C and (15)N chemical shift assignments of the
      hydrophobin MPG1 from the rice blast fungus Magnaporthe oryzae.
AB  - Fungal hydrophobins are secreted proteins that self-assemble at
      hydrophobic:hydrophilic interfaces. They are essential for a variety of processes
      in the fungal life cycle, including mediating interactions with surfaces and
      infection of hosts. The fungus Magnaporthe oryzae, the causative agent of rice
      blast, relies on the unique properties of hydrophobins to infect cultivated rice
      as well as over 50 different grass species. The hydrophobin MPG1 is highly
      expressed during rice blast pathogenesis and has been implicated during host
      infection. Here we report the backbone and sidechain assignments for the class I
      hydrophobin MPG1 from the rice blast fungus Magnaporthe oryzae.

PMID- 22610312
TI  - Unexpected evolution of optical properties in Ir-Pt complexes upon repeat unit
      increase: towards an understanding of the photophysical behaviour of
      organometallic polymers.
AB  - The photophysical properties of [Ir]-[Pt]-[Ir]-[Pt]-[Ir] ([Ir] =
      [Ir(ppy)(2)(bpy*)](+) ([Pt] = trans-Pt(PBu(3))(2)(C=C)(2); ppyH = 2
      phenylpyridine); bpy* = bipyridyl;) reveal an unprecedented triplet energy
      transfer from the terminal iridiums to the central Ir subunit.

PMID- 22610313
TI  - Computational modeling of adherent cell growth in a hollow-fiber membrane
      bioreactor for large-scale 3-D bone tissue engineering.
AB  - The use of hollow-fiber membrane bioreactors (HFMBs) has been proposed for three
      dimensional bone tissue growth at the clinical scale. However, to achieve an
      efficient HFMB design, the relationship between cell growth and environmental
      conditions must be determined. Therefore, in this work, a dynamic double-porous
      media model was developed to determine nutrient-dependent cell growth for bone
      tissue formation in a HFMB. The whole hollow-fiber scaffold within the bioreactor
      was treated as a porous domain in this model. The domain consisted of two
      interpenetrating porous regions, including a porous lumen region available for
      fluid flow and a porous extracapillary space filled with a collagen gel that
      contained adherent cells for promoting long-term growth into tissue-like mass.
      The governing equations were solved numerically and the model was validated using
      previously published experimental results. The contributions of several
      bioreactor design and process parameters to the performance of the bioreactor
      were studied. The results demonstrated that the process and design parameters of
      the HFMB significantly affect nutrient transport and thus cell behavior over a
      long period of culture. The approach presented here can be applied to any cell
      type and used to develop tissue engineering hollow-fiber scaffolds.

PMID- 22610314
TI  - Modulation of theta phase synchronization in the human electroencephalogram
      during a recognition memory task.
AB  - To the extent that recognition memory relies on interactions among widely
      distributed neural assemblies across the brain, phase synchronization between
      brain rhythms may play an important role in meditating those interactions. As the
      theta rhythm is known to modulate in power during the recognition memory process,
      we aimed to determine how the phase synchronization of the theta rhythms across
      the brain changes with recognition memory. Fourteen human participants performed
      a visual object recognition task in a virtual reality environment.
      Electroencephalograms were recorded from the scalp of the participants while they
      either recognized objects that had been presented previously or identified new
      objects. From the electroencephalogram recordings, we analyzed the phase-locking
      value of the theta rhythms, which indicates the degree of phase synchronization.
      We found that the overall phase-locking value recorded during the recognition of
      previously viewed objects was greater than that recorded during the
      identification of new objects. Specifically, the theta rhythms became strongly
      synchronized between the frontal and the left parietal areas during the
      recognition of previously viewed objects. These results suggest that the
      recognition memory process may involve an interaction between the frontal and the
      left parietal cortical regions mediated by theta phase synchronization.

PMID- 22610316
TI  - [Effect of experimentally created disordered occlusion on the expression of IL
      1beta, IL-6 and TNF-alpha in condylar cartilage of rats].
AB  - PURPOSE: To investigate the effect of the experimentally created malocclusion
      (ECDO) on the expression of IL-1beta, IL-6 and TNF-alpha in mandibular condylar
      cartilage of Sprague Dawley (SD) rats. METHODS: In the experimental group, the
      malocclusion was created by moving the first and third molars 0.8 mm away. HE and
      immunohistochemical staining were performed on the mandibular condyle at the end
      of the 8th or 12th week. Gene expression was analyzed by real-time PCR. The data
      was processed using SPSS12.0 software package. RESULTS: Degenerative changes were
      found in the experimental group, the level of IL-1beta was not significantly
      different among the groups (P>0.05), while the expression of IL-6 in 8-week ECDO
      subgroup was significantly higher than that in 8-week control subgroup (P=0.009),
      and the expression of TNF-alpha in 8-week ECDO subgroup was significantly higher
      than that in 8-week control subgroup (P=0.001) and 12-week ECDO subgroup
      (P=0.004). CONCLUSIONS: At the early period, IL-6 and TNF-alpha, but not IL
      1beta, play an important role in the degenerative remodeling procedure in rat
      condylar cartilage induced by ECDO.

PMID- 22610317
TI  - [Experimental study on the bonding strength between FCVA film and titanium].
AB  - PURPOSE: To study the bonding strength between the FCVA (filtered cathode vacuum
      arc) film and the titanium substrate. METHODS: According to the Engineer Manual
      of Germany (VDI3198), the indentation test was applied to evaluate the bonding
      strength between the FCVA film and the titanium substrate. The structure of the
      FCVA film and the interface between the film and the substrate were observed by
      means of scanning electron microscope(SEM). RESULTS: The fracture pattern of the
      film was classified as HF3 at the load of 400N, the bonding strength was enough
      between the FCVA film and the titanium substrate. SEM photograph showed the
      thickness of the FCVA film was about 1.2MUm equably and the film bonded to the
      substrate well. CONCLSION: The bonding strength between the FCVA film and the
      titanium substrate was enough to meet clinical demand.

PMID- 22610315
TI  - Carbohydrate to carbohydrate interaction in development process and cancer
      progression.
AB  - Two types of carbohydrate to carbohydrate interaction (CCI) have been known to be
      involved in biological processes. One is the CCI between molecules expressed on
      interfacing cell membranes of different cells to mediate cell to cell adhesion,
      and subsequently induce cell signaling, and is termed trans-CCI. It has been
      indicated that the Le(x) to Le(x) interaction at the morula stage in mouse
      embryos plays an important role in the compaction process in embryonic
      development. GM3 to Gg3 or GM3 to LacCer interaction has been suggested to be
      involved in adhesion of tumor cells to endothelial cells, which is considered a
      crucial step in tumor metastasis. The other is the CCI between molecules
      expressed within the same microdomain of the cell surface membrane, and is termed
      cis-CCI. The interaction between ganglioside GM3, and multi (>3) GlcNAc termini
      of N-linked glycans of epidermal growth factor receptor (EGFR), has been
      indicated as the molecular mechanism for the inhibitory effect of GM3 on EGFR
      activation. Also, the complex with GM3 and GM2 has been shown to inhibit the
      activation of hepatocyte growth factor (HGF) receptor, cMet, through its
      association with tetraspanin CD82, and results in the inhibition of cell
      motility. Since CCI research is still limited, more examples of CCI in biological
      processes in development, and cancer progression will be revealed in the future.

PMID- 22610318
TI  - [Self-cleaning and antimicrobial properties of methacrylic acid coupled
      TiO(2)/PMMA denture base resin].
AB  - PURPOSE: To study the influence of TiO2 and methacrylic acid on self-cleaning and
      antimicrobial properties of denture base resin. METHODS: TiO2 (2%, 4%, 6%) and
      methacrylic acid were respectively added into two makers' denture base resins.
      The self-cleaning property was assayed with measuring the decomposition of
      methylthioninium chloride. The antimicrobial property was tested with the
      pellicle-sticking method. The data were analysed by SPSS 12.0 software package
      for two-way ANOVA. RESULTS: The self-cleaning and antimicrobial properties of
      samples were improved as TiO2 increased. Methacrylic acid had no significant
      influence on self-cleaning and antimicrobial properties of the samples. The
      decomposition ratio and antimicrobial ratio of MTi4% (Rijin) were 53.96% and
      71.42%, respectively. CONCLUSION: Methacrylic acid coupled TiO2/PMMA denture base
      resin enjoys good self-cleaning and antimicrobial properties.

PMID- 22610319
TI  - [Effect of experimental occlusal hypofunction and its recovery on mandibular bone
      mineral density in rats].
AB  - PURPOSE: To examine the effect of experimental occlusal hypofunction and recovery
      on mandibular bone mineral density (BMD). METHODS: Sixty Sprague-Dawley (SD) male
      rats were randomly divided into experimental occlusal hypofunction
      group,experimental occlusal recovery group and control group, with 20 rats in
      each group. They were killed under deep anaesthesia at 0-, 2-, 4-, 6-, and 8
      week, after that the mandibles were immediately removed for measuring the BMD of
      cancellous and cortical bone in the first molar region with micro-CT. SPSS12.0
      software package was used for statistical analysis. RESULTS: At 4-week, the
      cancellous bone density at the bifurcation of the root and the root apex
      decreased in the hypofunction group (P<0.05), whereas the cancellous bone density
      on the buccal and lingual sides became lower at 6-week compared with the control
      group (P<0.01), and they all lasted until the end of the experiment (P<0.01). In
      the recovery group, the density on the buccal side, lingual side and at the root
      apex except for the bifurcation of the root had recovered to normal level
      compared with the control group at 8-week. At 6- and 8-week, cortical bone
      density in the hypofunction group had reduced in the lingual middle and lingual
      basal cortical bone areas (P<0.05). However, there was no difference between the
      buccal side in hypofunction group and control group at all the time-points. The
      same results were observed between the buccal and lingual sides in the recovery
      group compared with control group. CONCLUSIONS: Experimental occlusal
      hypofunction could result in the decrease of BMD in both cancellous and cortical
      bone in rats. Recovery of occlusal hypofunction may restore decreased BMD in
      mandible.

PMID- 22610320
TI  - [Effect of induced-mineralization on the expression of SOST in human periodontal
      ligament cells].
AB  - PURPOSE: To investigate the effect of induced- mineralization on the expression
      of SOST gene in human periodontal ligament cells, and explore the effect of SOST
      on periodontal tissues. METHODS: Human periodontal ligament cells were cultured
      by tissue explant in vitro, the cells were continuously induced by mineralization
      solution for 7,14 and 21days.The mineralized ability, SOST and related osteogenic
      genes(ALP, OCN)expression were detected. The data was analyzed with SPSS 17.0
      software package. RESULTS: Under the condition of mineralization solution in
      culture medium,human periodontal ligament cells had stronger ALP activity and
      Alizarin red staining,SOST and related osteogenic genes(ALP,OCN) expression were
      significantly upregulated in a time-dependent manner(P<0.05). CONCLUSIONS: After
      continuous induced-mineralization culture, human periodontal ligament cells can
      express SOST mRNA and related osteogenic genes in a time-dependent manner, which
      suggests that SOST may play a role in the regeneration of periodontal tissues.

PMID- 22610321
TI  - [Effect of Carisolv on endodontic microleakage].
AB  - PURPOSE: To evaluate the effect of Carisolv on endodontic microleakage by
      establishing a fluid transport model using sodium nitrite as tracer. METHODS:
      Seventy extracted teeth were randomly divided into 5 groups, all the root canals
      were prepared with different chemical reagents, including Carisolv,3% hydrogen
      peroxide+ 2%tosylchloramide sodium,2.5% sodium hypochlorite,5% sodium
      hypochlorite(negative control)and distilled water(positive control),post spaces
      were prepared after cold lateral condensation, the samples were put on the model,
      concentration of sodium nitrite which penetrated from the coronal to the apical
      end was measured by diazo reaction at 1,2,4,7,10,15,20,25,30,35,40,45,50,55 and
      60 day. The data were analyzed by ANOVA using SPSS 11.5 software package.
      RESULTS: Sodium nitrite was not detected in negative control group from 1 day to
      60 days. High concentration of sodium nitrite was detected in positive control
      group at first day, concentration of sodium nitrite was higher than that of other
      four groups from 1day to 60 days(P<0.01). Concentration of sodium nitrite in
      Carisolv group was significantly lower than that of 3%hydrogen peroxide+ 2%
      tosylchloramide sodium group(P<0.01), also lower than that of 2.5% sodium
      hypochlorite group(P<0.05),except at 25,30,35 and 40 days. CONCLUSIONS: Carisolv
      can remove the smear layer, decrease the endodontic microleakage, seal the root
      canal better. The fluid transport model using sodium nitrite as tracer can be
      used to evaluate the endodontic microleakage objectively,sensitively and exactly.

PMID- 22610322
TI  - [Antimicrobial effect of various calcium hydroxide on Porphyromonas endodontalis
      in vitro].
AB  - PURPOSE: To compare the antimicrobial activity of Endocal, calcium hydroxide
      paste, Calxyl, Vitapex on Porphyromonas endodontalis(P.e). METHODS: (1) The
      antimicrobial activity of different calcium hydroxide on P.e was examined at
      different exposure times by dynamic nephelometry. (2) 85 freshly extracted single
      rooted human teeth were selected and cut at the amelocemental junction. All roots
      were randomly divided into five groups. The bacteria were incubated in each canal
      and were sampled and counted before and after enveloping five kinds of intercanal
      medicine seeded. Student's t test, One-way ANOVA were used with SPSS11.0 software
      package for statistical analysis. RESULTS: The bacteria from each group were
      reduced significantly after intracanal medication (P<0.05). The antibacterial
      efficacy of Endocal and calcium hydroxide paste were superior to others under
      dynamic nephelometry test (P<0.05). Endocal, calcium hydroxide paste, Calxyl,
      Vitapex had strong inhibitory effect on P.e from infected root canals, and the
      rate of bacteria clearance was 95%. The antimicrobial activity of Endocal was
      significantly greater than others (P<0.05). CONCLUSIONS: Endocal, calcium
      hydroxide paste, Calxyl and Vitapex were effective for intercanal disinfection.
      The antibacterial activity of Endocal is greater than Vitapex.

PMID- 22610323
TI  - [Evaluation of marginal adaptation of three different copings of metal-ceramic
      crowns].
AB  - PURPOSE: To evaluate the marginal adaptation of three different copings of metal
      ceramic crowns cast in high golden, cobalt-chrome and nickel-chrome alloy.
      METHODS: Thirty working dies were created from a single master die and used to
      fabricate thirty copings in each as the following groups: A(high golden alloy,
      n=10), B(cobalt-chrome alloy, n=10) and C(nickel-chrome alloy, n=10). All the
      metal copings were fabricated using the conventional lost wax casting technique.
      The restorations were seated on the master die, and high-resolution digital
      photographs were made of the marginal area on all four sides. The vertical
      marginal gap was then measured using a calibrated digital software program. One
      way ANOVA and LSD tests were used to determine the differences using SPSS11.5
      software package. RESULTS: The mean marginal gaps were group A:(72.9+/-29.3)MUm;
      group B(85.9+/-33.0)MUm and group C(94.1+/-44.9)MUm. There was significant
      difference among three groups(P(AB)<0.01,P(AC)<0.001,P(BC)<0.05). CONCLUSIONS:
      The marginal gaps of three different metal copings are all clinical acceptable.
      The high golden copings resulted in smaller marginal gaps than either cobalt
      chrome or nickel-chrome copings.

PMID- 22610324
TI  - [The methodological study of improving the detected rate of mandibular central
      incisor with two canals].
AB  - PURPOSE: To investigate the detected rate and modality of multiple canals in
      mandibular central incisor by 5 different methods and to compare the results and
      differences among the methods, in order to provide give theoretical evidence of
      choosing right method and treatment in clinic. METHODS: 176 mandibular central
      incisors were examined by 5 different methods,including radiograph at a
      horizontal angle of 0, macrography 15#K- file, dental operative microscope,
      spiral CT scanning, and dental cross section.  All statistical analysis was
      performed using SAS6.12 software package. Data of detected rate of these 5
      methods were compared using McNemar exact probability test. RESULTS: The result
      of dental cross section was the key standard, the rate in 176 mandibular central
      incisor was 9.66% with two canals, of which 4.55% were type II, 5.11% were type
      v. The detected rate of two-canal teeth was 0.00% by radiograph at a horizontal
      angle of 0, 2.84% by macroscopy15# K- file, 4.76% by dental operative microscope,
      and 9.09% by spiral CT scanning,respectively. The results from 5 methods were
      compared with each other by McNemar test to find out the difference. Validity of
      these 5 methods according to gamma was dental cross section > spiral CT scanning
      > dental operative microscope > macroscopy 15#K- file > radiograph at a
      horizontal angle of 0. CONCLUSIONS: Some mandibular central incisors have two
      canals, the clinicians should pay more attention to avoid missing canals. When
      radiograph at a horizontal angle of 0 and macroscopy 15#K- file can't effectively
      find two canals, we suggest using the other methods such as radiograph with an
      excursion angle, dental operative microscope and spiral CT scanning to make clear
      diagnosis.

PMID- 22610325
TI  - [Study of radiographic method of increasing vertical angle for identifying double
      root in maxillary premolar with cone-beam CT].
AB  - PURPOSE: To explore the feasibility of radiography method of increasing vertical
      angle for identifying double root in maxillary premolar with cone-beam computed
      tomography(CBCT). METHODS: Thirty-one patients with 109 maxillary premolars who
      needed CT scan for maxillary teeth were selected and scanned by CBCT. The
      interested region was chosen to reconstruct the image of maxillary premolar at
      axial, coronal and sagittal section. The actual diameter of root in maxillary
      premolar and the projection diameter at the center vertical angle of 45 degrees 
      and horizontal angle of 38.5 degrees  were measured with CBCT. The data was
      analyzed with SPSS12.0 software package for Student's t test. RESULTS: There were
      no significant differences between the actual diameter of double root tip which
      was (3.74+/-0.22)mm and projection diameter which was (3.69+/-0.16)mm of
      maxillary premolar at the central vertical angle of 45 degrees  and horizontal
      angle of 38.5 degrees  with CBCT (P>0.05); There were also no significant
      difference between the actual diameter of middle 1/3 section of buccal-lingual
      diameter (7.87+/-0.66)mm and projection diameter (7.95+/-0.52)mm of maxillary
      premolar at the center vertical angle of 45 degrees  and horizontal angle of 38.5
      degrees  with CBCT (P>0.05). CONCLUSION: CBCT can provide an evidence for
      radiographic method of increasing vertical angle for identifying double root of
      maxillary premolar.

PMID- 22610326
TI  - [Soft and hard tissue changes after orthodontic and orthognathic treatment in
      patients with skeletal Class III malformation].
AB  - PURPOSE: To investigate soft- and hard-tissue changes and the association of
      these changes after orthodontic and orthognathic treatment in patients with
      skeletal Class III malocclusion. METHODS: The sample consisted of 20 patients
      with skeletal class III malocclusion treated with bilateral sagittal split ramus
      osteotomy (BSSRO). Lateral cephalograms taken before and after treatment were
      analyzed. All data were analyzed with SPSS13.0 software package for paired t
      test. RESULTS: The distances of SNB, B and Pog to Y axis was smaller and ANB was
      larger after treatment. The labiomental angle, the distances of TLL,SB and TC to
      Y axis were smaller(P<0.01). The two pairs of SB-B and TC-Pog had linear
      correlation. The ratio was 1:1 and 0.84, respectively. The coefficient of
      determination R2 value of SB-B was 0.96 and the other was 0.97. CONCLUSIONS: The
      patients with Class III malocclusion treated with orthodontic treatment and BSSRO
      can achieve satisfactory outcome. The single mandibular surgery did not affect
      the maxillary soft tissues. The changes of upper lip and lower lip length were
      not affected. The ratio of SB-B and TC-Pog corresponding soft- and hard-tissue
      ratio was 1:1 and 0.84, respectively. The coefficient of determination R2 values
      was all over 0.9.

PMID- 22610327
TI  - [Study of the appearance difference of lower complete denture between functional
      and anatomic impression techniques].
AB  - PURPOSE: To compare the difference in oblique external ridge, oblique internal
      ridge and alveolar process crest of lower complete denture base made through
      functional impression and anatomic impression techniques. METHODS: Fifteen
      patients were chosen to treat with two kinds of complete dentures through
      functional impression and anatomic impression technique respectively. 3D laser
      scanner was used to scan the three-dimensional model of the denture base and the
      differences of the surface structural between two techniques in alveolar process
      crest, external and internal oblique ridges were analyzed, using paired t test
      with SPSS 12.0 software package. RESULTS: Between the two techniques, there were
      significant differences in the areas of internal and external oblique
      ridge(P<0.01); there was no significant difference in the main support
      areas(P>0.05). CONCLUSIONS: The results explain why there is less tenderness when
      functional impression technique is applied. The differences measured also
      indicate that sufficient buffering should be made in external and internal
      oblique ridge areas in clinic.

PMID- 22610328
TI  - [The reliability of dento-maxillary models created by cone-beam CT and rapid
      prototyping:a comparative study].
AB  - PURPOSE: To analyze the reliability of the dento-maxillary models created by cone
      beam CT and rapid prototyping (RP). METHODS: Plaster models were obtained from 20
      orthodontic patients who had been scanned by cone-beam CT and 3-D models were
      formed after the calculation and reconstruction of software. Then, computerized
      composite models (RP models) were produced by rapid prototyping technique. The
      crown widths, dental arch widths and dental arch lengths on each plaster model, 3
      D model and RP model were measured, followed by statistical analysis with
      SPSS17.0 software package. RESULTS: For crown widths, dental arch lengths and
      crowding, there were significant differences(P<0.05) among the 3 models, but the
      dental arch widths were on the contrary. Measurements on 3-D models were
      significantly smaller than those on other two models(P<0.05). Compared with 3-D
      models, RP models had more numbers which were not significantly different from
      those on plaster models(P>0.05). The regression coefficient among three models
      were significantly different(P<0.01), ranging from 0.8 to 0.9. But between RP and
      plaster models was bigger than that between 3-D and plaster models. CONCLUSIONS:
      There is high consistency within 3 models, while some differences were accepted
      in clinic. Therefore, it is possible to substitute 3-D and RP models for plaster
      models in order to save storage space and improve efficiency.

PMID- 22610329
TI  - [Presurgical alveolar molding using computer aided design in infants with
      unilateral complete cleft lip and palate].
AB  - PURPOSE: To establish a new method of presurgical alveolar molding using computer
      aided design(CAD) in infants with complete unilateral cleft lip and palate
      (UCLP). METHODS: Ten infants with complete UCLP were recruited. A maxillary
      impression was taken at the first examination after birth. The study model was
      scanned by a non-contact three-dimensional laser scanner and a digital model was
      constructed and analyzed to simulate the alveolar molding procedure with reverse
      engineering software (RapidForm 2006). The digital geometrical data were exported
      to produce a scale model using rapid prototyping technology. The whole set of
      appliances was fabricated based on these solid models. RESULTS: The digital model
      could be viewed and measured from any direction by the software. By the end of
      the NAM treatment before surgical lip repair, the cleft was narrowed and the
      malformation of alveolar segments was aligned normally, significantly improving
      nasal symmetry and nostril shape. CONCLUSIONS: Presurgical NAM using CAD could
      simplify the treatment procedure and estimate the treatment objective, which
      enabled precise control of the force and direction of the alveolar segments
      movement.

PMID- 22610330
TI  - [Imaging classification of maxillary impacted central incisors].
AB  - PURPOSE: To investigate the classification of maxillary impacted central incisors
      through three-dimensional images. METHODS: Based on the original Dicom data of
      the spiral computed tomography of 103 patients with maxillary impacted central
      incisors, the three-dimensional images of maxillary impacted central incisors
      were reconstructed by Mimics 10.0 software, and the characteristics were analyzed
      and a classification was proposed. RESULTS: There were 106 teeth included in this
      study, 74 teeth were located labially, including 33 inverted impacted teeth, 28
      horizontally impacted teeth, and 13 inclined teeth. 20 teeth were located in the
      palatal side, including 11 inclined teeth and 9 horizontally impacted teeth. 12
      teeth were within the bone, which can be divided into three categories based on
      the position of the crown and in accordance with the vertical, far to near, and
      horizontal direction. Type I was labially impacted incisor, including 3
      subdivisions: labially inclined impacted, labially horizontal impacted and
      labially inverted impacted. Type II was palatally impacted incisor, including 2
      subdivisions: palatally inclined impacted and palatally horizontal impacted. Type
      III was vertically impacted incisor. CONCLUSIONS: The maxillary impacted incisors
      can be divided into 3 categories based on three-dimensional directions, and
      subdivisions can be created in each group including labially (inclined,
      horizontal, inverted) impacted incisors, palatally (inclined, horizontal)
      impacted incisor and vertically impacted incisors.

PMID- 22610331
TI  - [The application of guided bone regeneration technique in the restoration of
      maxillary lateral incisor with bone defect].
AB  - PURPOSE: To evaluate the clinical effectiveness and the satisfaction on aesthetic
      effectiveness of application of guided bone regeneration (GBR) technique in
      maxillary lateral incisor implant site. METHODS: Ninety patients were selected
      who only lost maxillary lateral incisor and placed with 101 implants(the implant
      systems were 3i, Osstem, ITI, Ankylos, BLB). The final restorations were
      porcelain-fused-to-metal crowns.  Clinical and X-ray examinations were conducted
      and esthetic results were observed at 3, 6,12 months after dental implant
      prosthetics. RESULTS: The follow-up time was 12 months, all patients achieved
      successful implantation and good osseointegration around the implant. The
      esthetic results were perfect .Among the 90 cases, 90.7%, 92.8% and 95.5% of  the
      patients were satisfied with the final outcomes 3,6,12 months after prosthetics.
      CONCLUSIONS: Good clinical effectiveness and satisfaction on aesthetic
      effectiveness can be obtained with GBR technique applied in maxillary lateral
      incisor implant site. Appropriate use of GBR technique is the solution of bone
      defect of maxillary lateral incisor implant site.

PMID- 22610332
TI  - [Three-dimensional finite element analysis of mandibular bilateral sagitta1 split
      ramus osteotomy with rigid internal fixation].
AB  - PURPOSE: To study the biomechanical characteristics of mandibular bilateral
      sagittal split ramus osteotomy(BSSRO) fixed with absorbable plate or titanium
      plate. METHODS: Spiral CT scan and finite element software (Ansys)were used to
      establish the three-dimensional finite element model of BSSRO with absorbable
      plate or titanium plate. The stress distribution of the internal fixation and the
      displacement of splited mandible was calculated under three kinds of occlusion
      position. RESULTS: Under the same occlusion,the maximal displacement of splited
      mandible was basically similar.The maximal stress of fixation system was titanium
      plate > absorbable plate; double plates > single plates; superior plate >
      inferior plate in the double plates. With the same fixation mode, the maximal
      stress of the fixation system and the maximal displacement of splited mandible
      was incisor occlusion<premolar occlusion <molar occlusion. CONCLUSIONS: The
      stress shielding of internal fixation of double plate is greater than single
      plate. Rigid internal fixation materials has certain impaction on stress
      shielding, but titanium plate is greater than the absorbable plate. Incisor
      occlusion had significant harmful effects and should be avoided after surgery.

PMID- 22610333
TI  - [Treatment of infantile hemangiomas with long pulsed 1064nm laser and oral
      corticosteroids].
AB  - PURPOSE: To evaluate the clinical therapeutic efficacy on infantile hemangiomas
      using long pulsed 1064nm laser and oral corticosteroid. METHODS: One hundred and
      two infantile hemangiomas in the proliferating phase state were treated with long
      pulsed 1064nm laser, long pulsed 1064nm laser and oral corticosteroid .Color
      Doppler was used to detect the depth of tumor. Laser treatment  was conducted for
      1 to 3 sessions, and oral corticosteroid was one course for 12 weeks. The results
      were analyzed with SAS6.12 software package for Ridit test. RESULTS: Total
      response treated with long pulsed 1064nm laser, long pulsed 1064nm laser and oral
      corticosteroid were achieved in 12 cases(24.00%) and 14
      cases(26.92%)respectively, good response were achieved in 18 cases(36.00%) and 27
      cases(51.92%). There was significant difference between the two groups(P<0.05).
      Total response in patients with superficial lesions treated with long pulsed
      1064nm laser, long pulsed 1064nm laser and oral corticosteroid were achieved in 8
      cases(34.78%) and 7 cases(33.33%) respectively, while good response were achieved
      in 10 cases(43.48%) and 8 cases(38.10%).There was no significant difference
      between two groups(P>0.05).Total response in patients with deep lesions treated
      with long pulsed 1064nm laser, long pulsed 1064nm laser and oral corticosteroid
      were achieved in 4 cases(14.81%) and 7 cases(22.58%) respectively, good response
      were achieved in 8 cases(29.63%) and 19 cases(61.29%).There was significant
      difference between the two groups(P<0.05). CONCLUSION: Combined therapy with 
      long pulsed 1064nm laser and oral corticosteroid is effective for infantile deep
      seated hemangiomas in the proliferating stage.

PMID- 22610334
TI  - [Clinical effect of two different composite resins in filling Class IV cavity].
AB  - PURPOSE: To compare the clinical effect of Clearfil AP-X(TM) and 3M Filte k(TM)
      Z350 in filling Class IV cavity. METHODS: 200 teeth were divided into two groups
      after class-IV cavity preparation according to composite resin filling technique.
      These teeth were then filled by Clearfil AP-X(TM) (with Clearfil SE Bond) and 3M
      Filtek(TM) Z350 (with 3M Adper Prompt Bond) step by step according to the
      instruction manual. The clinical effect was evaluated and compared after 3
      months, 6 months, 1 year and 2 years respectively. The data were collected and
      analyzed with USPH&Ryge evaluation standard and SPSS13.0 software package.
      RESULTS: The result indicated that there was no significant difference between
      the two group at half a year and 1 year. At 2-year there was significant
      difference in secondary caries occurrence,attrition, marginal discrepancy,
      marginal color and color matching between them, 3M group was better than clearfil
      group, but there was no significant difference in other indexes between them.
      CONCLUSIONS: When filling Class IV cavity, compared to Clearfil AP-X(TM), 3M
      Filtek(TM) Z350 has more advantages, and worthy of wider clinical application.

PMID- 22610336
TI  - [Investigation about particularity of dental clinical digital photography].
AB  - Dental photography is one of the special field in photography because of the
      particularity of the technology and approach. Lack of depth of field is one of
      the most possible problems for new learners. In dental photography, the control
      of depth of field depends on aperture only, deep depth of field can be achieved
      by decreasing the aperture. The parameters of exposure include aperture, shutter
      speed, flash intensity and ISO, which control the exposure together. The area of
      pictures is controlled by proportion, with manual exposure for getting right
      exposure. Manual focusing is suggested instead of auto focusing. The appropriate
      technology, method and right area are the most important factors for dental
      photography, and later treatment has to be avoided.

PMID- 22610335
TI  - [Comparative study of complications among routine method,high speed turbine
      handpiece and piezosurgery device after extraction of impacted wisdom teeth].
AB  - PURPOSE: To investigate complications in extraction of complicated impacted
      wisdom teeth whose root apex near to the inferior alveolar nerve(IAN) by using
      routine method(chisels),high speed turbine handpiece and piezosurgery device
      respectively. METHODS: Three hundred qualified patients with impacted wisdom
      teeth were divided into three groups randomly,one hundred patients in group A
      were extracted by routine method, one hundred patients in group B were extracted
      by high speed turbine handpiece, and one hundred patients in group C were
      extracted by piezosurgery device. The operation time, postoperative pain
      duration,dry socket and IAN injury were compared between each two groups. All
      statistical analysis was performed using SPSS 13.0 software package. Differences
      between groups were compared using a paired t test (quantitative data) or Chi
      square test (qualitative data). RESULTS: The operation time in group A
      was(14.12+/-0.12)min, (7.22+/-0.15)min in group B, (25.23+/-0.32)min in group C;
      Significant difference was found between group A and group B(P<0.05), group B and
      group C(P<0.05),group A and group C(P<0.05).Postoperative pain duration
      was(62.15+/-1.51)h in group A, (48.23+/-1.23)h in group B, (14.34+/-O.80)h in
      group C; Significant difference was found between group A and group B(P<0.05),
      group B and group C(P<0.05),group A and group C(P<0.05).9 patients developed dry
      socket in group A, 2 in group B, and 1 in group C; Significant difference was
      found between group A and group B(P<0.05), group A and group C(P<0.05). Six
      patients had IAN injury in group A, 2 in group B, 0 in group C. Significant
      difference was found between group A and group C. CONCLUSIONS: Compared with
      routine method, high speed turbine is better in extraction of impacted wisdom
      teeth, which can shorten operation time, lessen postoperative complications.
      Although there was longer operation time compared with group A and B,
      piezosurgery device is more effective in reducing postoperative complications.

PMID- 22610337
TI  - [The use of degloving approach in the treatment of nasal-orbital-ethmoid
      fracture].
AB  - PURPOSE: To explore the method and effect of degloving approach in the treatment
      of nasal-orbital-ethmoid(NOE) complex fracture surgery. METHODS: Eleven cases of
      unilateral nasal-orbital-ethmoid fracture(NOE) were selected from Medical Center
      of Stomatology, Foshan Hospital of Traditional Chinese Medicine. 6 were orbital
      fracture, 5 were nasal fracture. All the patients were treated open reduction and
      rigid internal fixation or rhinoplasty via midfacial degloving approach. RESULTS:
      Eleven patients were followed up for 3 to 12 months, all patients had transient
      nasal crusting and bleeding,1 case had traumatic epiphora, 4 cases had
      infraorbital temporary numbness,1 case of crooked nose. CONCLUSIONS: The
      degloving approach can achieve the advantages of a widely exposed field for
      operation,no facial scar,and no complications such as nasal vestibular stenosis.
      It is worthy of wide clinical application.

PMID- 22610338
TI  - Application of cone beam computed tomography in facial imaging science.
AB  - The use of three-dimensional (3D) methods for facial imaging has increased
      significantly over the past years.  Traditional 2D imaging has gradually being
      replaced by 3D images in different disciplines, particularly in the fields of
      orthodontics, maxillofacial surgery, plastic and reconstructive surgery,
      neurosurgery and forensic sciences. In most cases, 3D facial imaging overcomes
      the limitations of traditional 2D methods and provides the clinician with more
      accurate information regarding the soft-tissues and the underlying skeleton. The
      aim of this study was to review the types of imaging methods used for facial
      imaging. It is important to realize the difference between the types of 3D
      imaging methods as application and indications thereof may differ. Since 3D cone
      beam computed tomography (CBCT) imaging will play an increasingly important role
      in orthodontics and orthognathic surgery, special emphasis should be placed on
      discussing CBCT applications in facial evaluations.

PMID- 22610339
TI  - [Review of the impact of orthodontic treatments on soft tissue profile].
AB  - There are some people who have demands on the soft tissue profile among the
      patients who search for even teeth.On the other hand,when drawing up a
      plan,orthodontists will consider the soft tissue analysis.This review is focused
      on the assessment way of soft tissue profile,impact of orthodontic treatments
      such as functional appliances, extraction treatment, etc on the profile.

PMID- 22610340
TI  - [Implant-supported overdenture after pectoralis major myocutaneous flap
      reconstruction of tongue/floor of the mouth cancer:a case report].
AB  - Patients with oral cancer, undergoing ablative surgery, were left with severe
      deformities and dysfunction. Although the defect can be repaired by flap
      transplantation, there were still difficulties to restore normal oral structure
      and function of the oral cavity. In these instances, rehabilitation of
      mastication and occlusion is of the utmost importance. This article described the
      procedure that implants were inserted and bar/clips retained overdenture was
      applied to a patient who underwent reconstruction with pectoralis major
      myocutaneous flap after cancer ablation surgery. The patient's oral structure and
      functions was recovered, and the quality of life was greatly improved.

PMID- 22610341
TI  - Lanthanide(III) 2-naphthoxide complexes stabilized by interligand non-covalent
      interactions.
AB  - Lithium-lanthanide-2-naphthoxide complexes are found to have solvent dependent
      solution structures and related monomeric/dimeric solid state structures. The
      incorporation of tetramethylguanidium cations into lanthanide 2-naphthoxide
      complexes stabilizes a complex structure both in solution and the solid state
      through bridging hydrogen bonds between the 2-naphthoxide ligands.

PMID- 22610342
TI  - Histology-specific therapy for advanced soft tissue sarcoma and benign connective
      tissue tumors.
AB  - Molecularly targeted agents have shown activity in soft tissue sarcoma (STS) and
      benign connective tissue tumors over the past ten years, but response rates
      differ by histologic subtype. The field of molecularly targeted agents in sarcoma
      is increasingly complex. Often, clinicians must rely on phase II data or even
      case series due to the rarity of these diseases. In subtypes with a clear role of
      specific factors in the pathophysiology of disease, such as giant cell tumor of
      the bone and diffuse-type tenosynovial giant cell tumor, it is reasonable to
      treat with newer targeted therapies, when available, in place of chemotherapy
      when systemic treatment is needed to control disease. In diseases without
      documented implication of a pathway in disease pathogenesis (e.g. soft tissue
      sarcoma and vascular endothelial growth factor), clear benefit from drug
      treatment should be established in randomized phase III trials before
      implementation into routine clinical practice. Histologic subtype will continue
      to emerge as a critical factor in treatment selection as we learn more about the
      molecular drivers of tumor growth and survival in different subtypes. Many of the
      drugs that have been recently developed affect tumor growth more than survival,
      therefore progression-free survival may be a more clinically relevant
      intermediate endpoint than objective response rate using Response Evaluation
      Criteria In Solid Tumors (RECIST) in early phase sarcoma trials. Because of the
      rarity of disease and increasing need for multidisciplinary management, patients
      with connective tissue tumors should be evaluated at a center with expertise in
      these diseases. Participation in clinical trials, when available, is highly
      encouraged.

PMID- 22610344
TI  - Evidence of a rudimentary colon in the elasmobranch, Leucoraja erinacea.
AB  - The transition from aquatic to terrestrial life presented tetrapodamorphs with
      the challenge of maintaining water homeostasis and preventing desiccation on
      land. The colon evolved in terrestrial vertebrates to help maintain fluid
      balance. Although marine elasmobranchs lack a colon, their spiral intestine
      contains a subregion that histologically appears to be colon-like, possibly
      representing an evolutionary precursor to terrestrial digestive tracts. The
      distal-most region of the spiral intestine of elasmobranchs has no villi and a
      large number of acid mucins: hallmarks of water absorption in the colons of
      terrestrial animals. To determine if histologically distinct regions of the
      elasmobranch digestive tract correspond to functional differences, we compared
      water absorption in different subregions of the skate, Leucoraja erinacea
      digestive tract. Water absorption in stomach and spiral intestinal sacs was
      linear with time and not hydrostatic pressure-dependent. The histologically
      distinct distal portion of the spiral intestine had a threefold higher rate of
      water absorption than the proximal portion of the spiral intestine. In addition,
      the water-selective, colon-specific aquaporin 4 is expressed strongly in the
      distal spiral intestine epithelia, correlating with the region of the spiral
      intestine exhibiting the greatest rate of water absorption. We demonstrate that
      the distal spiral intestine is histologically and functionally distinct from the
      rest of the spiral intestine and represents a rudimentary colon within the
      vertebrate lineage.

PMID- 22610343
TI  - Genetic variants in antioxidant genes are associated with diisocyanate-induced
      asthma.
AB  - Diisocyanates are a common cause of occupational asthma, but risk factors are not
      well defined. A case-control study was conducted to investigate whether genetic
      variants of antioxidant defense genes, glutathione S-transferases (GSTM1, GSTT1,
      GSTM3, GSTP1), manganese superoxide dismutase (SOD2), and microsomal epoxide
      hydrolase (EPHX1) are associated with increased susceptibility to diisocyanate
      induced asthma (DA). The main study population consisted of 353 Caucasian French
      Canadians from among a larger sample of 410 diisocyanate-exposed workers in three
      groups: workers with specific inhalation challenge (SIC) confirmed DA (DA(+), n =
      95); symptomatic diisocyanate workers with a negative SIC (DA(-), n = 116); and
      asymptomatic exposed workers (AW, n = 142). Genotyping was performed on genomic
      DNA, using a 5'-nuclease PCR assay. The SOD2 rs4880, GSTP1 rs1695, and EPHX1
      rs2740171 variants were significantly associated with DA in both univariate and
      multivariate analyses. In the first logistic regression model comparing DA(+) and
      DA(-) groups, SOD2 rs4880, GSTM1 (null), GSTP1 rs762803, and EPHX1 rs2854450
      variants were associated with DA (p = 0.004, p = 0.047, p = 0.021, p <0.001,
      respectively). Genotype combinations GSTT1*GSTP1 rs762803, GSTM1*EPHX1 rs2854450,
      EPHX1 rs2740168*EPHX1 rs1051741, and GSTP1 rs762803*EPHX1 rs2740168 were also
      associated with DA in this model (p = 0.027, p = 0.002, p = 0.045, p = 0.044, 
      respectively). The GSTP1 rs1695 and EPHX1 rs1051741 and rs2740171 variants showed
      an association with DA in the  second model comparing DA(+) and AW groups (p =
      0.040, p = 0.019, p = 0.002, respectively). The GSTM3 rs110913*EPHX1 rs1051741
      genotype combination was also associated with DA under this model (p = 0.042).
      The results suggest that variations in SOD2, GST, and EPHX1 genes and their
      interactions contribute to DA susceptibility.

PMID- 22610346
TI  - A functional pectin methylesterase inhibitor protein (SolyPMEI) is expressed
      during tomato fruit ripening and interacts with PME-1.
AB  - A pectin methylesterase inhibitor (SolyPMEI) from tomato has been identified and
      characterised by a functional genomics approach. SolyPMEI is a cell wall protein
      sharing high similarity with Actinidia deliciosa PMEI (AdPMEI), the best
      characterised inhibitor from kiwi. It typically affects the activity of plant
      pectin methylesterases (PMEs) and is inactive against a microbial PME. SolyPMEI
      transcripts were mainly expressed in flower, pollen and ripe fruit where the
      protein accumulated at breaker and turning stages of ripening. The expression of
      SolyPMEI correlated during ripening with that of PME-1, the major fruit specific
      PME isoform. The interaction of SolyPMEI with PME-1 was demonstrated in ripe
      fruit by gel filtration and by immunoaffinity chromatography. The analysis of the
      zonal distribution of PME activity and the co-localization of SolyPMEI with high
      esterified pectins suggest that SolyPMEI regulates the spatial patterning of
      distribution of esterified pectins in fruit.

PMID- 22610348
TI  - Investigation of the correlates and effectiveness of a prison-based wellness
      program.
AB  - In 2006, a comprehensive wellness intervention, titled Wellness Works, was
      implemented in an incarcerated male population at a 200-bed facility in LaGrange,
      Kentucky. The purpose of this study was to determine health risk factors and
      benefits of program participation by analyzing data from a pre-/post
      participation health risk assessment (HRA). In total, 448 inmates completed the
      pre- HRA and 177 (40%) completed the post- HRA. Among program completers, two of
      the six measured domains (smoking and depression) showed significant improvement
      at the post- HRA while the other domains (exercise, nutrition, stress, and dental
      hygiene) did not show significant changes. Overall, this study shows positive
      signs of improving the health of the incarcerated population with this wellness
      program, but also points to the need for a controlled study.

PMID- 22610347
TI  - Identification of sense and antisense transcripts regulated by drought in
      sugarcane.
AB  - Sugarcane is an important sugar and energy crop that can be used efficiently for
      biofuels production. The development of sugarcane cultivars tolerant to drought
      could allow for the expansion of plantations to sub-prime regions. Knowledge on
      the mechanisms underlying drought responses and its relationship with carbon
      partition would greatly help to define routes to increase yield. In this work we
      studied sugarcane responses to drought using a custom designed oligonucleotide
      array with 21,901 different probes. The oligoarrays were designed to contain
      probes that detect transcription in both sense and antisense orientation. We
      validated the results obtained using quantitative real-time PCR (qPCR). A total
      of 987 genes were differentially expressed in at least one sample of sugarcane
      plants submitted to drought for 24, 72 and 120 h. Among them, 928 were sense
      transcripts and 59 were antisense transcripts. Genes related to Carbohydrate
      Metabolism, RNA Metabolism and Signal Transduction were selected for gene
      expression validation by qPCR that indicated a validation percentage of 90%. From
      the probes presented on the array, 75% of the sense probes and 11.9% of the
      antisense probes have signal above background and can be classified as expressed
      sequences. Our custom sugarcane oligonucleotide array provides sensitivity and
      good coverage of sugarcane transcripts for the identification of a representative
      proportion of natural antisense transcripts (NATs) and sense-antisense transcript
      pairs (SATs). The antisense transcriptome showed, in most cases, co-expression
      with respective sense transcripts.

PMID- 22610350
TI  - Olprinone and colforsin daropate alleviate septic lung inflammation and apoptosis
      through CREB-independent activation of the Akt pathway.
AB  - Olprinone, a specific phosphodiesterase III inhibitor, and corforsin daropate, a
      direct adenylate cyclase activator, are now being used in critical conditions. We
      investigated whether their therapeutic use provides protection against septic
      acute lung injury (ALI) and mortality. Polymicrobial sepsis was induced by cecal
      ligation and puncture (CLP) in BALB/c mice. Olprinone or colforsin daropate was
      continuously given through an osmotic pump that was implanted into the peritoneal
      cavity immediately following CLP. These treatments prevented the ALI development
      in CLP mice, as indicated by the findings that severe hypoxemia, increased
      pulmonary vascular permeability, and histological lung damage were strikingly
      remedied. Furthermore, continued administration of olprinone or colforsin
      daropate suppressed apoptosis induction in septic lungs and improved the survival
      of CLP mice. Olprinone and corforsin daropate enhanced Akt phosphorylation in
      septic lungs. Wortmannin, which inhibits the Akt upstream regulator
      phosphatidylinositol 3-kinase, abrogated the protective effects of olprinone and
      corforsin daropate on sepsis-associated lung inflammation and apoptosis. In vivo
      transfection of cyclic AMP response element binding protein (CREB) decoy
      oligodeoxynucleotide failed to negate the abilities of these agents to increase
      Akt phosphorylation and to inhibit IkappaBalpha degradation in septic lungs.
      These results demonstrate for the first time that CREB-independent Akt-mediated
      signaling is a critical mechanism contributing to the therapeutic effects of
      olprinone and corforsin daropate on septic ALI. Moreover, our data also suggest
      that these cyclic AMP-related agents, by blocking both nuclear factor-kappaB
      activation and apoptosis induction, may represent an effective therapeutic
      approach to the treatment of the septic syndrome.

PMID- 22610351
TI  - CD40 amplifies Fas-mediated apoptosis: a mechanism contributing to emphysema.
AB  - Excessive apoptosis and prolonged inflammation of alveolar cells are associated
      with the pathogenesis of pulmonary emphysema. We aimed to determine whether CD40
      affects alveolar epithelial cells and endothelial cells, with regard to evoking
      apoptosis and inflammation. Mice were repeatedly treated with agonistic-anti CD40
      antibody (Ab), with or without agonistic-anti Fas Ab, and evaluated for apoptosis
      and inflammation in lungs. Human pulmonary microvascular endothelial cells and
      alveolar epithelial cells were treated with agonistic anti-CD40 Ab and/or anti
      Fas Ab to see their direct effect on apoptosis and secretion of proinflammatory
      molecules in vitro. Furthermore, plasma soluble CD40 ligand (sCD40L) level was
      evaluated in patients with chronic obstructive pulmonary disease (COPD). In mice,
      inhaling agonistic anti-CD40 Ab induced moderate alveolar enlargement. CD40
      stimulation, in combination with anti-Fas Ab, induced significant emphysematous
      changes and increased alveolar cell apoptosis. CD40 stimulation also enhanced IFN
      gamma-mediated emphysematous changes, not via apoptosis induction, but via
      inflammation with lymphocyte accumulation. In vitro, Fas-mediated apoptosis was
      enhanced by CD40 stimulation and IFN-gamma in endothelial cells and by CD40
      stimulation in epithelial cells. CD40 stimulation induced secretion of CCR5
      ligands in endothelial cells, enhanced with IFN-gamma. Plasma sCD40L levels were
      significantly increased in patients with COPD, inversely correlating to the
      percentage of forced expiratory volume in 1 s and positively correlating to low
      attenuation area score by CT scan, regardless of smoking history. Collectively
      CD40 plays a contributing role in the development of pulmonary emphysema by
      sensitizing Fas-mediated apoptosis in alveolar cells and increasing the secretion
      of proinflammatory chemokines.

PMID- 22610349
TI  - Molecular mechanisms of MMP9 overexpression and its role in emphysema
      pathogenesis of Smad3-deficient mice.
AB  - Previous studies have found that inappropriate elevation of matrix
      metalloproteinase-9 (MMP9) expression and activity is coincident with early onset
      of emphysema in Smad3-null mice. Herein, we further investigated the role of
      increased MMP9 in emphysema pathogenesis and the related molecular regulatory
      mechanisms of elevated MMP9 in Smad3-null lung. Genetic blockade of MMP9 in Smad3
      null mice significantly attenuated emphysema pathology but not
      hypoalveolarization during early postnatal lung development. Furthermore, Smad3
      was found to be a transcription factor to positively regulate a protein
      deacetylase sirtuin 1 (SIRT1) by binding to an AP-1 site of SIRT1 promoter. A
      synergistic regulatory effect on SIRT1 expression was also detected between Smad3
      and c-Jun. Consistently, Smad3 knockout lung at P28 had reduced SIRT1 expression,
      which in turn resulted in increased acetylation of histone H3 at the
      transcription factor activator protein 1 (AP-1), NF-kappaB, and Pea3 binding
      sites of MMP9 promoter and increased acetylation of NF-kappaB. In addition,
      increased Pea3 expression and nuclear accumulation was also detected in Smad3
      null lungs at P28. Consistently, bindings of acetylated NF-kappaB and Pea3 to the
      MMP9 promoter were elevated in Smad3-null lung. We thus propose that deficiency
      of Smad3 causes downregulation of SIRT1 and increased Pea3 expression/nuclear
      accumulation, respectively. Decreased SIRT1 activity resulted in increased
      acetylation of histone H3 and NF-kappaB. Subsequently, increased bindings of
      transcription factors including NF-kappaB and Pea3 to MMP9 promoter significantly
      upregulate MMP9 transcription, contributing to emphysema pathogenesis.

PMID- 22610352
TI  - Interfacial stress affects rat alveolar type II cell signaling and gene
      expression.
AB  - Previous work from our group (Ravasio A, Hobi N, Bertocchi C, Jesacher A, Dietl
      P, Haller T. Am J Physiol Cell Physiol 300: C1456-C1465, 2011.) showed that
      contact of alveolar epithelial type II cells with an air-liquid interface (I(AL))
      leads to a paradoxical situation. It is a potential threat that can cause cell
      injury, but also a Ca(2+)-dependent stimulus for surfactant secretion. Both
      events can be explained by the impact of interfacial tensile forces on cellular
      structures. Here, the strength of this mechanical stimulus became also apparent
      in microarray studies by a rapid and significant change on the transcriptional
      level. Cells challenged with an I(AL) in two different ways showed
      activation/inactivation of cellular pathways involved in stress response and
      defense, and a detailed Pubmatrix search identified genes associated with several
      lung diseases and injuries. Altogether, they suggest a close relationship of
      interfacial stress sensation with current models in alveolar micromechanics.
      Further similarities between I(AL) and cell stretch were found with respect to
      the underlying signaling events. The source of Ca(2+) was extracellular, and the
      transmembrane Ca(2+) entry pathway suggests the involvement of a mechanosensitive
      channel. We conclude that alveolar type II cells, due to their location and
      morphology, are specific sensors of the I(AL), but largely protected from
      interfacial stress by surfactant release.

PMID- 22610353
TI  - Phase II and gene expression analysis trial of neoadjuvant capecitabine plus
      irinotecan followed by capecitabine-based chemoradiotherapy for locally advanced
      rectal cancer: Hoosier Oncology Group GI03-53.
AB  - PURPOSE: We designed this study in locally advanced rectal cancer to determine
      the pathological response, toxicity, and disease-free survival (DFS) with
      induction capecitabine plus irinotecan followed by capecitabine-based
      chemoradiotherapy (CRT) and analyze the gene expression of enzymes involved in
      the metabolism of capecitabine and irinotecan for associations with response and
      toxicity. METHODS: Patients with T3/T4 or node positive rectal cancer were
      treated with capecitabine 1,000 mg/m(2) twice daily (BID) days 1-14, and
      irinotecan 200 mg/m(2) on day 1 every 21 days for 2 cycles, followed by
      capecitabine 825 mg/m(2) BID days 1-5 per week with concurrent radiotherapy 50.4
      Gy in 28 fractions. Surgical resection occurred a median of 7.4 weeks after CRT.
      Gene expression levels or sequencing were used to analyze carboxylesterase
      converting enzymes (CES1, CES2), thymidylate synthase (TS), thymidine
      phosphorylase (TP), dehydropyrimidine dehydrogenase (DPD), topoisomerase I (TOPO
      I), and uridine-diphosphate (UDP) glucuronosyl transferase 1A1 in pre- and post
      treatment tumor and normal tissue samples. RESULTS: Twenty-two patients were
      enrolled, and 18 completed neoadjuvant therapy and underwent R0 resection. Two
      patients with UGT1A1 7/7 had grade 3 and 4 neutropenic fever and sepsis.
      Pathological complete response (pCR) occurred in 6 of 18 patients (33 %) and 10
      (56 %) had tumor and/or nodal downstaging. The 3-year DFS was 75.5 % (95 % CI,
      39.7-91.8 %). Locoregional control rate was 100 %. We observed higher TP gene
      expression in pCR patients, but no correlations with toxicity. CONCLUSIONS: This
      neoadjuvant regimen was safe and demonstrated significant antitumor activity.
      High TP tumor gene expression was associated with obtaining pCR.

PMID- 22610354
TI  - Tumor and non-tumor tissues differential oxidative stress response to
      supplemental DHA and chemotherapy in rats.
AB  - PURPOSE: Developing approaches that will increase the selectivity of anticancer
      drugs remains a challenge. Docosahexaenoic acid (DHA) has the potential to
      increase tumor sensitivity to chemotherapy with no sensitization of normal
      tissues. This study was aimed at exploring the mechanism involved in this
      differential sensitization with a focus on oxidative stress, one of the main
      determinants involved in DHA enhancement of anthracycline-based chemotherapy.
      METHODS: In a previously validated model of chemically induced mammary tumors in
      rats where supplemental DHA sensitized tumors to epirubicin, DHA level, lipid
      hydroperoxides (LPO), total antioxidant activity, glutathione peroxidase (GPx),
      and superoxide dismutase (SOD) activities were measured in tumors, intestine,
      liver, and heart in rats treated with DHA+epirubicin and in control rats (palm
      oil, no chemotherapy). RESULTS: At baseline, the level of LPO was similar in
      tumors, liver, heart, and small intestine. The proportion of DHA was higher in
      non-tumor tissues compared to tumors (liver or heart, p < 0.0001; intestine, p =
      0.01). DHA and epirubicin induced a significant increase in LPO in tumors (p =
      0.03), but no increase was detected in liver, heart, or intestine. The difference
      in LPO production between these tissues was associated with differences in their
      antioxidant defenses. In tumors, the adjustment of GPx activity was possible but
      limited, and no adjustment of their total antioxidant and SOD activities was
      observed compared to other tissues. CONCLUSION: Supplementing DHA during an
      anthracycline-based chemotherapy induced a selective increase of LPO in tumors.
      This selectivity might result from a differential handling of oxidative stress
      between tumor and non-tumor tissues.

PMID- 22610355
TI  - Area under the curve calculation of nedaplatin dose used in combination
      chemotherapy with irinotecan in a phase I study of gynecologic malignancies.
AB  - PURPOSE: Although the pharmacokinetic mechanism of nedaplatin (NDP) is similar to
      carboplatin, the dose of NDP is typically determined by body surface area and not
      by the area under the curve (AUC). We conducted a phase I study to determine the
      AUC-calculated optimal dosage of NDP used in combination chemotherapy with
      irinotecan (CPT-11) for gynecologic malignancies. METHODS: A total of 15 patients
      who were to undergo combination chemotherapy consisting of NDP and CPT-11 were
      enrolled in this study. The dose of CPT-11 was administered at a fixed dose of 60
      mg/m(2) and that of NDP was gradually increased from 8 to 12 MUg h/mL (AUC). The
      individual dose of NDP was calculated based on creatinine clearance of the
      patient according following formula: Dose(NDP) = AUC * CL(NDP), where CL(NDP) =
      0.0738 * creatinine clearance + 4.47 (Ishibashi's formula). RESULTS: One patient
      had dose-limiting toxicity (DLT) at level 1, and two patients suffered DLT at
      level 3. The dosage of NDP at AUC 12 was determined to be the maximum tolerated
      dose in combination chemotherapy with CPT-11, even though only two of the six
      patients showed DLT at level 3. CONCLUSIONS: The recommended dosage of NDP
      calculated by AUC with Ishibashi's formula was set to AUC 10 in combination
      chemotherapy with CPT-11.

PMID- 22610356
TI  - Loss of PTEN expression as a predictor of resistance to anti-EGFR monoclonal
      therapy in metastatic colorectal cancer: evidence from retrospective studies.
AB  - PURPOSE: To investigate the predictive value of loss of PTEN expression in
      patients with metastatic colorectal cancer (mCRC) treated with anti-EGFR
      monoclonal therapy. METHODS: Studies were systematically identified to
      investigate the relationship between PTEN expression and clinical outcome in mCRC
      patients treated with anti-EGFR MoAbs. Clinical outcomes included objective
      response rate (ORR), progression-free survival (PFS) and overall survival (OS).
      The pooled relative risk (RR) or hazard ratio (HR) was estimated using a fixed
      effects model or a random-effects model according to the heterogeneity between
      the studies. RESULTS: A total of 852 patients were included in the final meta
      analysis. The rate of loss of PTEN expression was 28.4% (242/852). The overall
      pooled RR for ORR was 0.413 (95% confidence intervals (CI), 0.177-0.965) when
      patients with loss of PTEN expression were compared with those with normal PTEN
      expression. Anti-EGFR monoclonal therapy resulted in improved PFS (HR, 0.466; 95%
      CI, 0.292-0.640) and OS (HR, 0.689 [95% CI, 0.482-0.896]) in patients unselected
      by KRAS mutation with normal PTEN expression over loss of PTEN expression. A
      better prognosis, as reflected by PFS (HR, 0.344; 95% CI, 0.154-0.533) and OS
      (HR, 0.544; 95% CI, 0.285-0.803), was observed in wild-type KRAS patients with
      normal PTEN expression versus loss of expression. CONCLUSIONS: Loss of expression
      of PTEN is a potential biomarker for resistance to anti-EGFR monoclonal therapy,
      particularly in mCRC patients with KRAS wild type.

PMID- 22610357
TI  - Identities: never the same again?
AB  - In response to the suggestion of treating identity as a historically bound notion
      (Matusov and Smith Integrative Psychological and Behavioral Science 46, 2012),
      its genealogy is further explored. First establishing that identity has been
      understood in a particular personal way, and that genealogy might carry beyond
      this conception, as it also carries beyond the notions of class and adolescence
      that are used to contextualize identity. Then opting for treating historically
      bound notions as dynamic, studying them in the continuous interaction between
      conceptualization and practice, as processes and verbs rather than essences and
      substantives. Finally suggesting to dissociate identity from selfhood by looking
      at why, when and to whom we need to identify ourselves and also inverting the
      question: why and when do we ask others to identify themselves? After all,
      sameness and difference are two sides of a coin called identity, and what is
      looked at is a matter of how it is looked at.

PMID- 22610358
TI  - Response time models of delta plots with negative-going slopes.
AB  - Delta plots (DPs) graphically compare reaction time (RT) quantiles obtained under
      two experimental conditions. In some research areas (e.g., Simon effects),
      decreasing delta plots (nDPs) have consistently been found, indicating that the
      experimental effect is largest at low quantiles and decreases for higher
      quantiles. nDPs are unusual and intriguing: They imply that RT in the faster
      condition is more variable, a pattern predicted by few standard RT models. We
      describe and analyze five classes of well-established latency mechanisms that are
      consistent with nDPs--exhaustive processing models, correlated stage models,
      mixture models, cascade models, and parallel channels models--and discuss the
      implications of our analyses for the interpretation of DPs. DPs generally do not
      imply any specific processing model; therefore, it is more fruitful to start from
      a specific quantitative model and to compare the DP it predicts with empirical
      data.

PMID- 22610359
TI  - Obesity cardiomyopathy and systolic function: obesity is not independently
      associated with dilated cardiomyopathy.
AB  - Obesity is a growing worldwide problem and the prevalence of heart failure is
      also on the rise. Obesity itself is an independent risk factor for the
      development of heart failure and the case of obesity-related heart failure is
      thought to be multifactorial. Obesity leads to increased central and total blood
      volumes along with decreased systemic arterial resistance resulting in high
      cardiac output state related adaptations in the cardiac structure. Persistence of
      these hemodynamic changes ultimately results in diastolic dysfunction, however,
      whether these changes progress to significant systolic dysfunction or not is
      doubtful. Some MUGA (Multi Gated Acquisition) scan-based studies had shown mild
      degree of left ventricular systolic dysfunction in the obese, however, these
      findings could not be confirmed with recent echocardiogram-based studies. Using
      extensive literature review, we found no evidence of obesity-related
      cardiomyopathy leading to significant systolic dysfunction fulfilling criterion
      for the diagnosis of dilated cardiomyopathy (LVEF <35 %). Therefore, any obese
      patient presenting with severe LV dysfunction should prompt further
      investigations to evaluate for the underlying etiology.

PMID- 22610360
TI  - Durable resistance to stripe rust is due to three specific resistance genes in
      French bread wheat cultivar Apache.
AB  - Quantitative resistance is postulated to be more durable than qualitative (R-gene
      mediated) resistance, which is usually quickly overcome by the pathogen
      population. Despite its wide use for nearly 10 years in France, the French bread
      wheat cultivar Apache remains resistant to stripe rust. Here, we investigated the
      genetic architecture of cv. Apache resistance to examine whether its durability
      could be explained by quantitative characteristics. We identified quantitative
      trait loci (QTL) by composite interval mapping of disease progress data recorded
      throughout 4 years of field assays. These assays included inoculation with three
      different pathotypes on a segregating population originating from a cross between
      cv. Apache and cv. Taldor, a French cultivar susceptible to stripe rust. Three
      QTLs derived from Apache, QYr.inra-2AS, QYr.inra-2BL and QYr.inra-4B, were
      detected. Each of these QTLs contributed between approximately 15 and 69 % of the
      phenotypic variance and corresponds to a race-specific resistance gene. We showed
      that QYr.inra-2AS and QYr.inra-2BS map to the positions of Yr17 and Yr7,
      respectively, whereas QYr.inra-4B corresponds to an adult plant resistance gene.
      Our results demonstrate that a combination of two or more race-specific
      resistance genes can confer durable resistance provided that it is properly
      managed at a continental level. Race-specific resistance genes should not be
      removed from breeding programs provided that they are properly managed.

PMID- 22610361
TI  - The impact of provider volume on the outcomes after surgery for lumbar spinal
      stenosis.
AB  - BACKGROUND: Investigation into the provider volume-outcomes association for
      patients undergoing spine surgery has been limited. OBJECTIVE: To examine the
      impact of surgeon and hospital volume on the outcomes after decompression with or
      without fusion for lumbar spinal stenosis. METHODS: Data from the Nationwide
      Inpatient Sample (2005-2008) were retrospectively extracted. Multivariate
      logistic regression analyses were performed to calculate the adjusted odds of in
      hospital mortality and the development of a postoperative complication with
      increasing surgeon or hospital volume. Provider volume was evaluated continuously
      and categorically, divided by percentiles into quintiles. Very-low-volume
      surgeons performed < 15 procedures over 4 years. All analyses were adjusted for
      differences in patient age, sex, comorbidities, and primary payer, as well as
      hospital bed size, teaching status, and location (urban vs rural). RESULTS: A
      total of 48,971 admissions were examined. In-hospital mortality did not differ
      significantly with increasing provider volume. When examined continuously,
      greater surgeon volume was associated with a significantly lower adjusted odds of
      developing a complication (odds ratio, 0.72; 95% confidence interval, 0.65-0.78;
      P < .001). Patients who underwent surgery by very-low-volume surgeons (odds
      ratio, 1.38; 95% confidence interval, 1.19-1.60; P = .001), but not those treated
      by low-, medium-, or high-volume surgeons, had a significantly higher
      complication rate compared with those who underwent surgery by very high-volume
      surgeons. After adjustment for surgeon volume, hospital volume was not
      significantly associated with in-hospital mortality or complications. CONCLUSION:
      In this nationwide study, patients treated by very-low-volume surgeons had a
      significantly higher complication rate compared with those treated by very high
      volume surgeons.

PMID- 22610363
TI  - Metabolomic response of human skin tissue to low dose ionizing radiation.
AB  - Understanding how human organs respond to ionizing radiation (IR) at a systems
      biology level and identifying biomarkers for IR exposure at low doses can help
      provide a scientific basis for establishing radiation protection standards.
      Little is known regarding the physiological responses to low dose IR at the
      metabolite level, which represents the end-point of biochemical processes inside
      cells. Using a full thickness human skin tissue model and GC-MS-based metabolomic
      analysis, we examined the metabolic perturbations at three time points (3, 24 and
      48 h) after exposure to 3, 10 and 200 cGy of X-rays. PLS-DA score plots revealed
      dose- and time-dependent clustering between sham and irradiated groups.
      Importantly, delayed metabolic responses were observed at low dose IR. When
      compared with the high dose at 200 cGy, a comparable number of significantly
      changed metabolites were detected 48 h after exposure to low doses (3 and 10 cGy)
      of irradiation. Biochemical pathway analysis showed perturbations to DNA/RNA
      damage and repair, lipid and energy metabolisms, even at low doses of IR.

PMID- 22610362
TI  - Sesame seed food allergy.
AB  - The number of reports regarding sesame seed food allergy (SFA) has increased
      significantly worldwide over the past two decades, either due to a genuine
      increase in SFA or merely an increase in its awareness. Its prevalence is
      difficult to estimate due to the lack of well designed prospective population
      based studies. Based on the available data, we estimate that SFA affects 0.1-0.2
      % of the population, in areas where the food is available. Albeit this prevalence
      appears to be relatively low, it is approximately one-half of that of persistent
      cow's milk allergy. While only one fatality has been reported, the significant
      number of SFA patients presenting as anaphylaxis indicates the potential risk.
      Many reports based the diagnosis of SFA on sensitization criteria alone,
      particularly amongst atopic dermatitis patients. Elimination of sesame from the
      diet of these children utilizing such criteria is not justified, and may even
      increase the risk for developing SFA.

PMID- 22610364
TI  - Do sepsis biomarkers in the emergency room allow transition from bundled sepsis
      care to personalized patient care?
AB  - PURPOSE OF REVIEW: There is convincing evidence linking early start of fluid
      resuscitation and initiation of appropriate antimicrobial therapy to improved
      outcomes in patients with sepsis in the emergency department. Blood biomarkers
      measured on admission and during follow-up have the ability to guide early sepsis
      recognition, severity assessment and therapeutic decisions in individual patients
      and may allow transition from bundled sepsis care to more individualized
      management in single patients. RECENT FINDINGS: Although a large number of
      promising diagnostic and prognostic biomarkers have been put forward in
      observational studies, only few have been evaluated in prospective randomized
      controlled intervention trials. Markers such as lactate for risk stratification
      and guidance of fluid resuscitation, procalcitonin for assessing risk of
      bacterial infections and guiding therapeutic decisions about initiation and
      duration of antimicrobial therapy, and recently proadrenomedullin for early
      mortality prediction and site-of-care decisions in respiratory infections, have
      shown to improve patient management. SUMMARY: For few biomarkers, recent study
      results demonstrate that well defined clinical protocols have the potential to
      guide decisions about the individual risk stratification and treatment of
      patients with suspicion of sepsis ultimately leading to improved patient care and
      outcomes. For other biomarkers, promising observation data have been put forward,
      but their potential needs to be evaluated in large-scale, well designed
      prospective intervention studies before clinical use can be recommended.

PMID- 22610365
TI  - Perioperative morbidity:  lessons from recent clinical trials.
AB  - PURPOSE OF REVIEW: To identify the recent literature supporting the ability of
      anesthesiologists to impact morbidity and mortality outside of the immediate
      intraoperative period. RECENT FINDINGS: Hemodynamic management designed to
      optimize cardiac output and stroke volume can significantly lower the risk of
      perioperative morbidity, and, in some cases, mortality. The implications of the
      POISE trial, which upended the previously accumulating data in support of
      indiscriminate perioperative beta-blockade by demonstrating worsened outcomes,
      were supported by high-quality, propensity-matched, prospectively collected data.
      Data supporting the safety of colloid use has been threatened by the retraction
      of 88 publications of a single author, as well as prospective, nonrandomized
      data, suggesting increased renal morbidity in critically ill patients receiving
      synthetic colloids. Large datasets continue to suggest an association between red
      blood cell transfusion and mortality. Analysis of the operating room strongly
      implicates anesthesia providers as a potential mechanism for bacterial
      contamination. SUMMARY: Anesthesiologists should consider implication of goal
      directed therapy in high-risk surgical patients, adhere to the American College
      of Cardiology/American Heart Association guidelines with regard to perioperative
      beta-blockade, critically assess the data to support their choice of synthetic
      colloids over crystalloids, explore all possible strategies for avoiding
      perioperative transfusion, and be cognizant of their potential contribution to
      perioperative infectious morbidity.

PMID- 22610366
TI  - Corticosterone regulates the expression of neuropeptide Y and reelin in MLO-Y4
      cells.
AB  - Osteocytes that have a dendritic appearance are widely believed to form a complex
      cellular network system and play crucial roles in mechanotransduction as a
      principal bone mechanosensor, which is the basis of their neuronallike biology,
      as previously reported. Neuropeptide Y (NPY) and reelin mRNA, which are brain
      specific neurogenic markers, have been identified in osteocytes. However, changes
      in the production of NPY and reelin in response to specific biochemical
      stimulation are unknown. In this study, we investigated the in vitro effect of
      corticosterone, one of the endogenous glucocorticoids, on the expression of NPY
      and reelin in the MLO-Y4 osteocyte cell line. Cells were treated with
      corticosterone at different concentrations (10(-9) M-10(-5) M) for 1, 3, 6, 12
      and 24 h. As revealed, corticosterone reduced the MLO-Y4 cell viability and
      proliferation in a dose- and time-dependent manner based on an MTT assay and a Vi
      CELL analyzer. The cells were then incubated with corticosterone (10(-6) MUM),
      and the NPY and reelin expression levels were detected at 1, 3, 6, 12 and 24 h
      using real-time PCR and Western blot analysis. These results demonstrated that at
      the gene and the protein levels, corticosterone significantly upregulated the NPY
      and reelin expression in a time-dependent manner. The application of a
      glucocorticoid receptor antagonist, RU486, reversed the reduced cell viability
      and the increased expression of NPY and reelin that were caused by
      corticosterone. To the best of our knowledge, this is the first report to verify
      that corticosterone regulates the NPY and reelin expression in osteocytes.

PMID- 22610368
TI  - Spirometry: an essential tool for screening, case-finding, and diagnosis of COPD.

PMID- 22610367
TI  - Overexpression of Arabidopsis translationally controlled tumor protein gene
      AtTCTP enhances drought tolerance with rapid ABA-induced stomatal closure.
AB  - Translationally controlled tumor protein (TCTP), also termed P23 in human,
      belongs to a family of calcium- and tubulin-binding proteins, and it is generally
      regarded as a growth-regulating protein. Recently, Arabidopsis TCTP (AtTCTP) has
      been reported to function as an important growth regulator in plants. On the
      other hand, plant TCTP has been suggested to be involved in abiotic stress
      signaling such as aluminum, salt, and water deficit by a number of microarray or
      proteomic analyses. In this study, the biological functions of AtTCTP were
      investigated by using transgenic Arabidopsis plants overexpressing AtTCTP.
      Interestingly, AtTCTP overexpression enhanced drought tolerance in plants. The
      expression analysis showed that AtTCTP was expressed in guard cells as well as in
      actively growing tissues. Physiological studies of the overexpression lines
      showed increased ABA- and calcium-induced stomatal closure ratios and faster
      stomatal closing responses to ABA. Furthermore, in vitro protein-protein
      interaction analysis confirmed the interaction between AtTCTP and microtubules,
      and microtubule cosedimentation assays revealed that the microtubule binding of
      AtTCTP increased after calcium treatment. These results demonstrate that the
      overexpression of AtTCTP confers drought tolerance to plants by rapid ABA
      mediated stomatal closure via the interaction with microtubules in which calcium
      binding enhances the interaction. Collectively, the present results suggest that
      the plant TCTP has molecular properties similar to animal TCTPs, such as tubulin-
      and calcium-binding, and that it functions in ABA-mediated stomatal movement, in
      addition to regulating the growth of plants.

PMID- 22610369
TI  - Rates and correlates of HIV and STI infection among homeless women.
AB  - We studied the prevalence of biologically confirmed HIV, Chlamydia, and gonorrhea
      in a randomly selected sample of sheltered homeless women in New York City, and
      explored their association with demographic, homeless history, and clinical risk
      factors. 329 women were randomly selected from 28 family and single adult
      shelters. The estimated prevalence of HIV in the study sample is 0.6 % (+/-0.3
      %); for Chlamydia it is 6.7 % (+/-2.2 %); for gonorrhea it is 0.9 % (+/-0.04 %).
      A history of childhood sexual abuse, arrest history, current psychotic symptoms,
      and substance use disorder placed women at greater risk of infection. We consider
      contextual factors that may yield underestimates of HIV prevalence in our sample
      and discuss how a more comprehensive prevalence estimate might be constructed.
      Findings underscore the importance of offering HIV/STI testing, counseling, and
      HIV risk prevention interventions to homeless women and suggest that
      interventions should be tailored to the needs of specific subgroups of homeless
      women.

PMID- 22610371
TI  - Assessing priorities for combination HIV prevention research for men who have sex
      with men (MSM) in Africa.
AB  - A consultation was hosted in South Africa (March 2011) to assess the combination
      HIV prevention research priorities of academics, implementers and MSM community
      leaders. Sixty-nine participants, representing 17 African countries,
      participated. Interactive strategies were used to present current data on HIV
      interventions and discussions on research possibilities were facilitated with
      research priorities identified using the nominal group technique. Data were
      analysed using directed content analysis. Health worker training, social
      mobilisation, and community engagement were prioritised as structural
      interventions. Comprehensive counselling was identified as the most important
      behavioural intervention, with adherence, mental health, and risk reduction
      counselling identified as key counselling topics. Rectal microbicides, oral pre
      exposure prophylaxis and condom and lubricant distribution were the most
      important biomedical interventions. This consultation resulted in the first
      combination HIV prevention research agenda for MSM in Africa. Outcomes will
      inform future research and be used to advocate for combination approaches to HIV
      prevention for MSM.

PMID- 22610370
TI  - Text messaging reduces HIV risk behaviors among methamphetamine-using men who
      have sex with men.
AB  - Text-messaging interventions present a novel approach for targeting high-risk men
      who have sex with men (MSM) who may not respond to or may be difficult to reach
      for face-to-face or site-based interventions. Project Tech Support (N = 52) was
      an open label pilot study testing the feasibility and utility of a text-messaging
      intervention to reduce methamphetamine use and high-risk sexual behaviors among
      out-of-treatment MSM. Participants in the two-week intervention received social
      support and health education text messages transmitted in real-time. At follow
      up, there were significant decreases in frequency of methamphetamine use and
      unprotected sex while on methamphetamine (both p < 0.01), and a significant
      increase in self-reported abstinence from methamphetamine use (13.3 % vs. 48.9 %;
      p < 0.001). Additionally, participants reported reductions of unprotected anal
      intercourse with HIV-positive partners (p < 0.01); with HIV-negative partners,
      participants reported fewer insertive and receptive episodes (both p < 0.05).
      Findings demonstrate that text messaging is a promising intervention for reaching
      and potentially changing HIV high-risk behaviors among out-of-treatment,
      methamphetamine-using MSM.

PMID- 22610372
TI  - Costs, consequences and feasibility of strategies for achieving the goals of the
      National HIV/AIDS strategy in the United States: a closing window for success?
AB  - Three key policy questions are explored here: Is it still epidemiologically
      feasible to attain the incidence and transmission rate reduction goals of the
      U.S. National HIV/AIDS Strategy (NHAS) by 2015? If so, what costs will be
      incurred in necessary program expansion, and will the investment be cost
      effective? Would substantial expansion of prevention services for persons living
      with HIV (PLWH) augment the other strategies outlined in the NHAS in terms of
      effectiveness and cost-effectiveness? Eight policy scenarios were constructed
      based on three factors (two levels each): expansion (or not) of HIV diagnostic
      services; assumptions regarding levels of effectiveness of HIV treatment in
      achieving suppressed viral load; and possible levels of expansion of prevention
      services for PLWH. All scenarios assumed that the NHAS goal of 85 % linkage to
      HIV care would be fully achieved by 2015. Standard methods of economic evaluation
      and epidemiologic modeling were employed. Each of the eight policy scenarios was
      compared to a flat transmission rate comparison condition; then, key policy dyads
      were compared pairwise. Without expansion of diagnostic services and of
      prevention services for PLWH, scaling up coverage of HIV care and treatment alone
      in the U.S. will not achieve the incidence and transmission rate reduction goals
      of the NHAS. However, timely expansion of testing and prevention services for
      PLWH does allow for the goals to still be achieved by 2015, and does so in a
      highly cost-effective manner.

PMID- 22610373
TI  - "It's important to take your medication everyday okay?" An evaluation of
      counselling by lay counsellors for ARV adherence support in the Western Cape,
      South Africa.
AB  - There is growing interest in standard care programmes for antiretroviral (ARV)
      adherence support. In South Africa, individual counselling following ARV
      initiation is a main strategy for supporting adherence in the public sector.
      Egan's client-centred "Skilled Helper" counselling model is the predominant model
      used in HIV counselling in this context. This study evaluated counselling
      delivered by lay ARV adherence counsellors in Cape Town in terms of adherence to
      Egan's model. Thirty-eight transcripts of counselling sessions with non-adherent
      patients were analysed based on the methods of content analysis. These sessions
      were conducted by 30 counsellors. Generally counsellors' practice adhered neither
      to Egan's model nor a client-centred approach. Inconsistent with evidence-based
      approaches to counselling for ARV adherence support, counsellors mainly used
      information-giving and advice as strategies for addressing clients' non
      adherence. Recommendations for improving practice are made. The question as to
      how appropriate strategies from developed countries are for this setting is also
      raised.

PMID- 22610374
TI  - Formation of reactive impurities in aqueous and neat polyethylene glycol 400 and
      effects of antioxidants and oxidation inducers.
AB  - A 2,4-dinitrophenylhydrazine (DNPH) precolumn derivatization high-performance
      liquid chromatography-ultraviolet detection (HPLC-UV) method was developed to
      quantify levels of formaldehyde and acetaldehyde in polyethylene glycol (PEG)
      solutions. Formic acid and acetic acid were quantified by HPLC-UV. Samples of
      neat and aqueous PEG 400 solutions were monitored at 40 degrees C and 50 degrees
      C to determine effects of excipient source, water content, pH, and trace levels
      of hydrogen peroxide or iron metal on the formation of reactive impurities. The
      effects of antioxidants were also evaluated. Formic acid was the major
      degradation product in nearly all cases. The presence of water increased the rate
      of formation of all impurities, especially formic acid as did the presence of
      hydrogen peroxide and trace metals. Acidic pH increased the formation of
      acetaldehyde and acetic acid. A distribution of unidentified degradation products
      formed in neat PEG 400 disappeared upon addition of HCl with corresponding
      increase of formic acid, indicating they were likely to be PEG-formyl esters.
      Other unidentified degradation products reacted with DNPH to form a distribution
      of derivatized products likely to be PEG aldehydes. Antioxidants butylated
      hydroxyanisole, butylated hydroxytoluene, propyl gallate d-alpha tocopheryl
      polyethylene glycol-1000 succinate, and sodium metabisulfite were effective in
      limiting reactive impurity formation, whereas ascorbic acid and acetic acid were
      not.

PMID- 22610376
TI  - Electronic structure and solution behavior of a tris(N,N'
      diphenylhydrazido)manganese(IV) propeller complex.
AB  - The electronic structure and magnetic properties of the manganese(IV)
      trihydrazide propeller complex, Li(2)Mn(kappa(2)-PhN-NPh)(3)L(2) (1, L =
      tetrahydrofuran, diethyl ether), are explored. EPR and solid-state magnetometry
      studies are indicative of a high spin Mn(IV) with a S = 3/2 spin state. Solution
      phase magnetic measurements result in a measured MU(eff) less than that expected
      for a S = 3/2, indicating a solution-phase equilibrium with a lower-spin species.
      Concentration-dependent magnetic susceptibility measurements identify clustering
      of 1 to an antiferromagnetically coupled multinuclear complex as the most likely
      explanation for the solution behavior. Comparative infrared spectroscopy in
      solution and solid phase are described which support speciation in solution.

PMID- 22610375
TI  - Synergistic effects of streptolysin S and streptococcal pyrogenic exotoxin B on
      the mouse model of group A streptococcal infection.
AB  - Streptococcus pyogenes is a group A streptococcus (GAS) and an important human
      pathogen that causes a variety of diseases. Streptococcal pyrogenic exotoxin B
      (SPE B) and streptolysin S (SLS) are important virulence factors involved in GAS
      infection, but it is not clear which one is more virulent. Using an air pouch
      infection model, the wild-type strain NZ131, its isogenic mutants, and
      complementary mutants were used to examine the effects of SPE B and SLS on GAS
      infection. The results of the skin lesion and mouse mortality assays showed that
      although SPE B and SLS had a synergistic effect on GAS infection, SPE B played a
      more important role in local tissue damage while SLS had a more prominent effect
      on mouse mortality. Surveys of the exudates from the air pouch revealed that the
      expression of inflammatory cytokines was significantly inhibited in the sagB/speB
      double-mutant JM4-infected mice. Furthermore, in vivo and in vitro studies showed
      that the isogenic mutant strains were more susceptible to the immune cell killing
      than the wild-type strain and that the sagB/speB-double-mutant JM4 was the most
      sensitive among these strains. Moreover, infection with the sagB/speB-double
      mutant JM4 strain caused the least amount of macrophage apoptosis compared to
      infection with the wild-type NZ131 and the other complementary strains, which
      express only SPE B or SLS or both. Taken together, these results indicate that
      both SPE B and SLS contributed to GAS evasion from immune cell killing, local
      tissue damage, and mouse mortality.

PMID- 22610377
TI  - Rapid-sequence induction of anesthesia in obstetric women: how safe is it?

PMID- 22610378
TI  - Keep our guard up against general anesthesia for cesarean section!

PMID- 22610379
TI  - Activation of AMP-activated protein kinase stimulates Na+,K+-ATPase activity in
      skeletal muscle cells.
AB  - Contraction stimulates Na(+),K(+)-ATPase and AMP-activated protein kinase (AMPK)
      activity in skeletal muscle. Whether AMPK activation affects Na(+),K(+)-ATPase
      activity in skeletal muscle remains to be determined. Short term stimulation of
      rat L6 myotubes with the AMPK activator 5-aminoimidazole-4-carboxamide-1-beta-d
      ribofuranoside (AICAR), activates AMPK and promotes translocation of the
      Na(+),K(+)-ATPase alpha(1)-subunit to the plasma membrane and increases
      Na(+),K(+)-ATPase activity as assessed by ouabain-sensitive (86)Rb(+) uptake.
      Cyanide-induced artificial anoxia, as well as a direct AMPK activator (A-769662)
      also increase AMPK phosphorylation and Na(+),K(+)-ATPase activity. Thus,
      different stimuli that target AMPK concomitantly increase Na(+),K(+)-ATPase
      activity. The effect of AICAR on Na(+),K(+)-ATPase in L6 myotubes was attenuated
      by Compound C, an AMPK inhibitor, as well as siRNA-mediated AMPK silencing. The
      effects of AICAR on Na(+),K(+)-ATPase were completely abolished in cultured
      primary mouse muscle cells lacking AMPK alpha-subunits. AMPK stimulation leads to
      Na(+),K(+)-ATPase alpha(1)-subunit dephosphorylation at Ser(18), which may
      prevent endocytosis of the sodium pump. AICAR stimulation leads to methylation
      and dephosphorylation of the catalytic subunit of the protein phosphatase (PP) 2A
      in L6 myotubes. Moreover, AICAR-triggered dephosphorylation of the Na(+),K(+)
      ATPase was prevented in L6 myotubes deficient in PP2A-specific protein
      phosphatase methylesterase-1 (PME-1), indicating a role for the PP2A.PME-1
      complex in AMPK-mediated regulation of Na(+),K(+)-ATPase. Thus contrary to the
      common paradigm, we report AMPK-dependent activation of an energy-consuming ion
      pumping process. This activation may be a potential mechanism by which exercise
      and metabolic stress activate the sodium pump in skeletal muscle.

PMID- 22610380
TI  - Caffeic acid phenethyl ester attenuates IgE-induced immediate allergic reaction.
AB  - Caffeic acid phenethyl ester (CAPE) is the active component of honey bee propolis
      extracts. The results of the current study demonstrate that CAPE attenuated
      immunoglobulin (Ig)E-mediated allergic response in mast cells. Oral
      administration of CAPE inhibited IgE-mediated passive cutaneous anaphylaxis. CAPE
      effectively reduced both histamine and serotonin (5-HT)-induced vascular
      permeability in rats. CAPE also reduced histamine and leukotrienes (LTs) release
      from isolated rat peritoneal mast cells. Moreover, CAPE suppressed contraction
      induced by histamine (3 * 10(-8)-3 * 10(-5) M), 5-HT (3 * 10(-9)-10(-6) M) and
      adenosine (3 * 10(-8)-10(-5) M) in guinea pig tracheal zigzag. These findings
      provide evidence that CAPE may serve as an effective therapeutic agent for
      allergic diseases.

PMID- 22610381
TI  - Nanoparticulate silver increases uric acid and allantoin excretion in rats, as
      identified by metabolomics.
AB  - Metabolomic investigation of rat urine was employed to identify mammalian
      metabolites affected by ionic or nanoparticulate silver. Female and male Wistar
      rats were administered silver nanoparticles (2.25, 4.5 or 9.0 mg kg(-1) body
      weight per day) or ionic silver (silver acetate, 9.0 mg silver kg(-1) bw per day)
      by oral gavage for 28 days. On day 18, urine was collected for 24 h and subjected
      to metabolomics with high performance liquid chromatography-quadropole time-of
      flight mass spectrometry (HPLC-QTOF-MS)-based separation and detection. Principal
      component analysis was subsequently applied to the data. Metabolomic differences
      in urine composition were found in female rats but not in male rats. Several
      metabolites were identified by the use of elemental composition calculated from
      the exact mass combined with searches in the Human Metabolome Database.The
      metabolite identities were eventually verified by co-chromatography with
      authentic standards. Differences were found in uric acid and its degradation
      product, allantoin. Administration of nanoparticulate silver increased both
      metabolites, whereas ionic silver only increased allantoin. In conclusion,
      metabolomic investigation of rat urine showed that increased levels of uric acid
      and allantoin were associated with exposure to nanoparticulate silver.

PMID- 22610382
TI  - Professionals' attitudes after a seclusion reduction program: anything changed?
AB  - Changing professionals' attitudes toward seclusion is seen as an important
      condition to reduce its use. The purpose of this study was to determine whether
      professionals from a mental health institute in the Netherlands changed in their
      attitudes toward seclusion after implementation of a multifaceted seclusion
      reduction program. Professionals working on four acute admission wards filled in
      the Professional Attitudes Toward Seclusion Questionnaire (PATS-Q) before and
      after a seclusion reduction program. Changes were analyzed by comparing mean
      scores on the PATS-Q. After the program, professionals scored significantly
      higher on 'ethics' and 'more care'. As expected, no change occurred on 'reasons'
      for the use of seclusion. In addition, no significant changes were found on
      'confidence', 'better care' and 'other care'. Significant changes in professional
      attitudes concerning the ethics of using seclusion and involving issues of more
      care were observed after a seclusion reduction program. Mental health
      professionals moved in the direction of 'transformers', indicating an increased
      criticism of the practice of seclusion and increased willingness to change their
      own use of seclusion.

PMID- 22610383
TI  - Type III hemifacial microsomia in a kitten.
AB  - The case described herein presented with craniofacial malformations resembling
      hemifacial microsomia (HFM), a congenital disorder described in humans. To our
      knowledge, this is the first reported case of HFM in a domestic cat.

PMID- 22610384
TI  - The natural history of cerebral dural arteriovenous fistulae.
AB  - BACKGROUND: Hemorrhage from cerebral dural arteriovenous fistulae (dAVF) is a
      considerable source of neurological morbidity and even mortality. OBJECTIVE: To
      evaluate the natural history of cerebral dAVF. METHODS: We reviewed our own
      cohort of 70 dAVF and incorporated results from the literature, synthesizing
      pooled hemorrhage rates and evaluating risk factors for 395 dAVF in 6 studies.
      RESULTS: No hemorrhages occurred during 409 lesion-years of follow-up of Borden
      type I dAVF; however, cortical venous drainage developed in 1.4%. Like type I
      dAVF, type II dAVF demonstrated a female predilection and were most commonly
      transverse-sigmoid or cavernous. Eighteen percent of type II dAVF presented with
      hemorrhage (95% confidence interval [CI]: 8%-36%), and the annual hemorrhage rate
      was 6% (95% CI: 0.1%-19%). Borden type III dAVF demonstrated a male predilection
      and were most commonly tentorial or petrosal. Thirty-four percent presented with
      hemorrhage (95% CI: 0.4%-49%), with an annual hemorrhage rate of 10% (95% CI: 4%
      20%), increasing to 21% for those with venous ectasia (95% CI: 4%-66%). The
      hemorrhage rate decreased to 2% for asymptomatic or minimally symptomatic type II
      or III dAVF (95% CI: 0.2%-8%), and increased to 10% for those presenting with
      nonhemorrhagic neurological deficits (95% CI: 0.9%-41%) and to 46% for those
      presenting with hemorrhage (95% CI: 11%-130%). CONCLUSION: Venous ectasia is a
      significant risk factor for hemorrhage among dAVF with cortical venous drainage.
      In addition, those with hemorrhagic presentation, even compared with
      nonhemorrhagic neurological deficit presentation, as well as Borden type III dAVF
      compared with type II dAVF demonstrated a trend toward greater hemorrhage rates.

PMID- 22610385
TI  - Management of fear of radiation exposure in carers of outpatients treated with
      iodine-131.
AB  - OBJECTIVE: To characterise potential fear of radiation exposure in a normal
      population of individuals who have volunteered to care for a radioactive family
      member or friend after outpatient radioimmunotherapy (RIT) treatment for cancer,
      and obtain their knowing and willing acceptance of the risk. METHODS: Over 750
      carers of 300 patients confined to their homes for 1 week following outpatient
      iodine-131 rituximab RIT of lymphoma were interviewed by a nuclear medicine
      physicist according to a multi-visit integrated protocol designed to minimise
      radiation exposure, define risk and gain informed consent. RESULTS: Median
      radiation exposure of carers was 0.49 mSv (range 0.01-3.7 mSv) which is below the
      Western Australian regulatory limit of 5 mSv for consenting adult carers of
      radioactive patients. After signing a declaration of consent, only 2 carers of
      750 abrogated their responsibility and none of those who carried out their duties
      expressed residual concerns at the end of the exit interview with respect to
      their radiation exposure. CONCLUSION: Fear of radiation exposure in a normal
      population may be characterised as a normal emotional response. In the special
      case of carers of radioactive patients, this fear may be successfully managed by
      rational, authoritative and empathic explanation to define the risk and gain
      willing acceptance within the context of domiciliary patient care.

PMID- 22610387
TI  - Lung amyloid nodule detected by 99mTc-aprotinin scintigraphy.
AB  - We present a case in which an amyloid lung nodule was diagnosed preoperatively by
      amyloid scintigraphy (99m)Tc-aprotinin. A 65-year-old man complained of marked
      weight loss (9 kg) over a period of 6 months. An abnormal shadow in the middle
      field of the right lung was detected on chest X-ray, corresponding to a 16-mm
      nodule in the right middle lobe on thoracic computed tomography (CT). Total
      protein and immunoglobulin G levels were elevated to 8.3 and 2245 mg/dl,
      respectively, but other blood tests including several tumor marker levels and
      Cryptococcus antibodies were all within normal range. Fluorodeoxyglucose positron
      emission tomography showed no uptake by the lung nodule, so lung amyloidosis was
      considered as differential diagnosis. To avoid risk of bleeding on bronchoscopy,
      noninvasive amyloid scintigraphy using (99m)Tc-aprotinin was first performed. A
      nodular, abnormal accumulation was observed in the right middle lung lobe.
      Diagnostic imaging strongly suggested amyloidosis, so video-assisted thoracic
      surgery was performed rather than bronchoscopy. Pathological samples showed
      positive staining with Congo red, and A-lambda amyloidosis was diagnosed on the
      basis of immunostaining. Scintigraphy using (99m)Tc-aprotinin offers a useful,
      noninvasive method for assessing lung amyloidosis.

PMID- 22610386
TI  - Superior prognostic utility of gross and metabolic tumor volume compared to
      standardized uptake value using PET/CT in head and neck squamous cell carcinoma
      patients treated with intensity-modulated radiotherapy.
AB  - OBJECTIVE: To compare the prognostic utility of the 2-[(18)F] fluoro-2-deoxy-D: 
      glucose (FDG) maximum standardized uptake value (SUV(max)), primary gross tumor
      volume (GTV), and FDG metabolic tumor volume (MTV) for disease control and
      survival in patients with head and neck squamous cell carcinoma (HNSCC)
      undergoing intensity-modulated radiotherapy (IMRT). METHODS: Between 2007 and
      2011, 41 HNSCC patients who underwent a staging positron emission tomography with
      computed tomography and definitive IMRT were identified. Local (LC), nodal (NC),
      distant (DC), and overall (OC) control, overall survival (OS), and disease-free
      survival (DFS) were assessed using the Kaplan-Meier product-limit method.
      RESULTS: With a median follow-up of 24.2 months (range 2.7-56.3 months) local,
      nodal, and distant recurrences were recorded in 10, 5, and 7 patients,
      respectively. The median SUV(max), GTV, and MTV were 15.8, 22.2 cc, and 7.2 cc,
      respectively. SUV(max) did not correlate with LC (p = 0.229) and OS (p = 0.661)
      when analyzed by median threshold. Patients with smaller GTVs (<22.2 cc)
      demonstrated improved 2-year actuarial LC rates of 100 versus 56.4 % (p = 0.001)
      and OS rates of 94.4 versus 65.9 % (p = 0.045). Similarly, a smaller MTV (<7.2
      cc) correlated with improved 2-year actuarial LC rates of 100 versus 54.2 % (p <
      0.001) and OS rates of 94.7 versus 64.2 % (p = 0.04). Smaller GTV and MTV
      correlated with improved NC, DC, OC, and DFS, as well. CONCLUSION: GTV and MTV
      demonstrate superior prognostic utility as compared to SUV(max), with larger
      tumor volumes correlating with inferior local control and overall survival in
      HNSCC patients treated with definitive IMRT.

PMID- 22610388
TI  - F-18 FDG uptake in borderline intraductal papillary neoplasms of the bile duct.
AB  - Intraductal papillary neoplasm of the bile duct (IPN-B) has been recently
      proposed as the biliary counterpart of intraductal papillary mucinous neoplasm of
      the pancreas. Histologically, IPN-B can be classified into adenoma, borderline,
      carcinoma in situ, and invasive carcinoma. Two patients with suspected
      intraductal tumor underwent fluorine-18 fluorodeoxyglucose positron emission
      tomography/computed tomography. One patient showed an FDG-avid tumor in the right
      liver with SUV(max) of 9.4 in early images and 11.3 in delayed images. The
      patient underwent complete tumor resection. Adenoma with high-grade dysplasia was
      confirmed by pathology. The other patient showed an FDG-avid polypoid lesion at
      the distal common bile duct with SUV(max) of 5.4. The lesion was endoscopically
      resected. Histopathologic findings showed adenoma with low-grade dysplasia. These
      two cases highlight that IPN-B should be included in the differential diagnosis
      of abnormal biliary intraductal FDG accumulation along with carcinoma, and
      inflammatory and infectious processes.

PMID- 22610389
TI  - Thallium-201 scintigraphy for the assessment of long-term prognosis in patients
      with osteosarcoma.
AB  - OBJECTIVE: The aim of this study was to confirm the prognostic value of (201)Tl
      scintigraphy in the midcourse of preoperative chemotherapy in patients with
      osteosarcoma. METHODS: The 28 patients with biopsy-proven osteosarcoma were
      enrolled retrospectively in this study. Planar scintigraphy was performed 15 min
      after injection of 111 MBq (201)Tl before preoperative chemotherapy and after
      third course (midcourse) of chemotherapy in all patients. The (201)Tl uptake
      ratio was calculated by dividing the count density of the lesion by that of the
      contralateral normal area. The percentage reduction of the (201)Tl uptake ratio
      calculated by 100 * [(pre-chemotherapy ratio - mid-chemotherapy ratio)/pre
      chemotherapy ratio] was compared with the histopathological response and long
      term survival rate. RESULTS: Good histopathological response was observed in 16
      patients. Mean follow-up period was 58.0 +/- 41 months. Both overall and event
      free survival rates of histopathologically good responders were significantly
      higher than that of poor responders (P = 0.018 and P = 0.0076). There was also
      significant correlation between pre-chemotherapeutic effect evaluated with
      (201)Tl scintigraphy and overall and event-free survival rate in all patients (P
      = 0.045 and P = 0.017, respectively), and in patients without metastasis at
      initial diagnosis (P = 0.043 and P = 0.031, respectively). CONCLUSION: (201)Tl
      scintigraphy performed in the middle of neoadjuvant chemotherapy can predict
      overall survival and event-free survival in patients with osteosarcoma.

PMID- 22610390
TI  - SPSS macros to compare any two fitted values from a regression model.
AB  - In regression models with first-order terms only, the coefficient for a given
      variable is typically interpreted as the change in the fitted value of Y for a
      one-unit increase in that variable, with all other variables held constant.
      Therefore, each regression coefficient represents the difference between two
      fitted values of Y. But the coefficients represent only a fraction of the
      possible fitted value comparisons that might be of interest to researchers. For
      many fitted value comparisons that are not captured by any of the regression
      coefficients, common statistical software packages do not provide the standard
      errors needed to compute confidence intervals or carry out statistical tests
      particularly in more complex models that include interactions, polynomial terms,
      or regression splines. We describe two SPSS macros that implement a matrix
      algebra method for comparing any two fitted values from a regression model. The
      !OLScomp and !MLEcomp macros are for use with models fitted via ordinary least
      squares and maximum likelihood estimation, respectively. The output from the
      macros includes the standard error of the difference between the two fitted
      values, a 95% confidence interval for the difference, and a corresponding
      statistical test with its p-value.

PMID- 22610391
TI  - Sleep-disordered breathing and cancer mortality: results from the Wisconsin Sleep
      Cohort Study.
AB  - RATIONALE: Sleep-disordered breathing (SDB) has been associated with total and
      cardiovascular mortality, but an association with cancer mortality has not been
      studied. Results from in vitro and animal studies suggest that intermittent
      hypoxia promotes cancer tumor growth. OBJECTIVES: The goal of the present study
      was to examine whether SDB is associated with cancer mortality in a community
      based sample. METHODS: We used 22-year mortality follow-up data from the
      Wisconsin Sleep Cohort sample (n = 1,522). SDB was assessed at baseline with full
      polysomnography. SDB was categorized using the apnea-hypopnea index (AHI) and the
      hypoxemia index (percent sleep time below 90% oxyhemoglobin saturation). The
      hazards of cancer mortality across levels of SDB severity were compared using
      crude and multivariate analyses. MEASUREMENTS AND MAIN RESULTS: Adjusting for
      age, sex, body mass index, and smoking, SDB was associated with total and cancer
      mortality in a dose-response fashion. Compared with normal subjects, the adjusted
      relative hazards of cancer mortality were 1.1 (95% confidence interval [CI], 0.5
      2.7) for mild SDB (AHI, 5-14.9), 2.0 (95% CI, 0.7-5.5) for moderate SDB (AHI, 15
      29.9), and 4.8 (95% CI, 1.7-13.2) for severe SDB (AHI >= 30) (P-trend = 0.0052).
      For categories of increasing severity of the hypoxemia index, the corresponding
      relative hazards were 1.6 (95% CI, 0.6-4.4), 2.9 (95% CI, 0.9-9.8), and 8.6 (95%
      CI, 2.6-28.7). CONCLUSIONS: Our study suggests that baseline SDB is associated
      with increased cancer mortality in a community-based sample. Future studies that
      replicate our findings and look at the association between sleep apnea and
      survival after cancer diagnosis are needed.

PMID- 22610392
TI  - The early spatio-temporal correlates and task independence of cerebral voice
      processing studied with MEG.
AB  - Functional magnetic resonance imaging studies have repeatedly provided evidence
      for temporal voice areas (TVAs) with particular sensitivity to human voices along
      bilateral mid/anterior superior temporal sulci and superior temporal gyri
      (STS/STG). In contrast, electrophysiological studies of the spatio-temporal
      correlates of cerebral voice processing have yielded contradictory results,
      finding the earliest correlates either at ~300-400 ms, or earlier at ~200 ms
      ("fronto-temporal positivity to voice", FTPV). These contradictory results are
      likely the consequence of different stimulus sets and attentional demands. Here,
      we recorded magnetoencephalography activity while participants listened to
      diverse types of vocal and non-vocal sounds and performed different tasks varying
      in attentional demands. Our results confirm the existence of an early voice
      preferential magnetic response (FTPVm, the magnetic counterpart of the FTPV)
      peaking at about 220 ms and distinguishing between vocal and non-vocal sounds as
      early as 150 ms after stimulus onset. The sources underlying the FTPVm were
      localized along bilateral mid-STS/STG, largely overlapping with the TVAs. The
      FTPVm was consistently observed across different stimulus subcategories,
      including speech and non-speech vocal sounds, and across different tasks. These
      results demonstrate the early, largely automatic recruitment of focal, voice
      selective cerebral mechanisms with a time-course comparable to that of face
      processing.

PMID- 22610395
TI  - Natural killer cells and hepatitis C: natural killer p46 expression linked to
      antiviral and antifibrotic activity.

PMID- 22610394
TI  - Phase-locked responses to speech in human auditory cortex are enhanced during
      comprehension.
AB  - A growing body of evidence shows that ongoing oscillations in auditory cortex
      modulate their phase to match the rhythm of temporally regular acoustic stimuli,
      increasing sensitivity to relevant environmental cues and improving detection
      accuracy. In the current study, we test the hypothesis that nonsensory
      information provided by linguistic content enhances phase-locked responses to
      intelligible speech in the human brain. Sixteen adults listened to meaningful
      sentences while we recorded neural activity using magnetoencephalography. Stimuli
      were processed using a noise-vocoding technique to vary intelligibility while
      keeping the temporal acoustic envelope consistent. We show that the acoustic
      envelopes of sentences contain most power between 4 and 7 Hz and that it is in
      this frequency band that phase locking between neural activity and envelopes is
      strongest. Bilateral oscillatory neural activity phase-locked to unintelligible
      speech, but this cerebro-acoustic phase locking was enhanced when speech was
      intelligible. This enhanced phase locking was left lateralized and localized to
      left temporal cortex. Together, our results demonstrate that entrainment to
      connected speech does not only depend on acoustic characteristics, but is also
      affected by listeners' ability to extract linguistic information. This suggests a
      biological framework for speech comprehension in which acoustic and linguistic
      cues reciprocally aid in stimulus prediction.

PMID- 22610393
TI  - Two distinct ipsilateral cortical representations for individuated finger
      movements.
AB  - Movements of the upper limb are controlled mostly through the contralateral
      hemisphere. Although overall activity changes in the ipsilateral motor cortex
      have been reported, their functional significance remains unclear. Using human
      functional imaging, we analyzed neural finger representations by studying
      differences in fine-grained activation patterns for single isometric finger
      presses. We demonstrate that cortical motor areas encode ipsilateral movements in
      2 fundamentally different ways. During unimanual ipsilateral finger presses,
      primary sensory and motor cortices show, underneath global suppression, finger
      specific activity patterns that are nearly identical to those elicited by
      contralateral mirror-symmetric action. This component vanishes when both motor
      cortices are functionally engaged during bimanual actions. We suggest that the
      ipsilateral representation present during unimanual presses arises because
      otherwise functionally idle circuits are driven by input from the opposite
      hemisphere. A second type of representation becomes evident in caudal premotor
      and anterior parietal cortices during bimanual actions. In these regions,
      ipsilateral actions are represented as nonlinear modulation of activity patterns
      related to contralateral actions, an encoding scheme that may provide the neural
      substrate for coordinating bimanual movements. We conclude that ipsilateral
      cortical representations change their informational content and functional role,
      depending on the behavioral context.

PMID- 22610396
TI  - Games of age-dependent prevention of chronic infections by social distancing.
AB  - Epidemiological games combine epidemic modelling with game theory to assess
      strategic choices in response to risks from infectious diseases. In most
      epidemiological games studied thus-far, the strategies of an individual are
      represented with a single choice parameter. There are many natural situations
      where strategies can not be represented by a single dimension, including
      situations where individuals can change their behavior as they age. To better
      understand how age-dependent variations in behavior can help individuals deal
      with infection risks, we study an epidemiological game in an SI model with two
      life-history stages where social distancing behaviors that reduce exposure rates
      are age-dependent. When considering a special case of the general model, we show
      that there is a unique Nash equilibrium when the infection pressure is a monotone
      function of aggregate exposure rates, but non-monotone effects can appear even in
      our special case. The non-monotone effects sometimes result in three Nash
      equilibria, two of which have local invasion potential simultaneously. Returning
      to a general case, we also describe a game with continuous age-structure using
      partial-differential equations, numerically identify some Nash equilibria, and
      conjecture about uniqueness.

PMID- 22610397
TI  - Symmetric competition as a general model for single-species adaptive dynamics.
AB  - Adaptive dynamics is a widely used framework for modeling long-term evolution of
      continuous phenotypes. It is based on invasion fitness functions, which determine
      selection gradients and the canonical equation of adaptive dynamics. Even though
      the derivation of the adaptive dynamics from a given invasion fitness function is
      general and model-independent, the derivation of the invasion fitness function
      itself requires specification of an underlying ecological model. Therefore,
      evolutionary insights gained from adaptive dynamics models are generally model
      dependent. Logistic models for symmetric, frequency-dependent competition are
      widely used in this context. Such models have the property that the selection
      gradients derived from them are gradients of scalar functions, which reflects a
      certain gradient property of the corresponding invasion fitness function. We show
      that any adaptive dynamics model that is based on an invasion fitness functions
      with this gradient property can be transformed into a generalized symmetric
      competition model. This provides a precise delineation of the generality of
      results derived from competition models. Roughly speaking, to understand the
      adaptive dynamics of the class of models satisfying a certain gradient condition,
      one only needs a complete understanding of the adaptive dynamics of symmetric,
      frequency-dependent competition. We show how this result can be applied to number
      of basic issues in evolutionary theory. 

PMID- 22610398
TI  - ADVANCE and glycaemia thresholds: a need to clarify the statistical approach.

PMID- 22610400
TI  - Exacerbation of diabetic nephropathy by hyperlipidaemia is mediated by Toll-like
      receptor 4 in mice.
AB  - AIMS/HYPOTHESIS: Hyperlipidaemia is an independent risk factor for the
      progression of diabetic nephropathy, but its molecular mechanism remains elusive.
      We investigated in mice how diabetes and hyperlipidaemia cause renal lesions
      separately and in combination, and the involvement of Toll-like receptor 4 (TLR4)
      in the process. METHODS: Diabetes was induced in wild-type (WT) and Tlr4 knockout
      (KO) mice by intraperitoneal injection of streptozotocin (STZ). At 2 weeks after
      STZ injection, normal diet was substituted with a high-fat diet (HFD). Functional
      and histological analyses were carried out 6 weeks later. RESULTS: Compared with
      treatment with STZ or HFD alone, treatment of WT mice with both STZ and HFD
      markedly aggravated nephropathy, as indicated by an increase in albuminuria,
      mesangial expansion, infiltration of macrophages and upregulation of pro
      inflammatory and extracellular-matrix-associated gene expression in glomeruli. In
      Tlr4 KO mice, the addition of an HFD to STZ had almost no effects on the
      variables measured. Production of protein S100 calcium binding protein A8
      (calgranulin A; S100A8), a potent ligand for TLR4, was observed in abundance in
      macrophages infiltrating STZ-HFD WT glomeruli and in glomeruli of diabetic
      nephropathy patients. High-glucose and fatty acid treatment synergistically
      upregulated S100a8 gene expression in macrophages from WT mice, but not from KO
      mice. As putative downstream targets of TLR4, phosphorylation of interferon
      regulatory factor 3 (IRF3) was enhanced in kidneys of WT mice co-treated with STZ
      and HFD. CONCLUSIONS/INTERPRETATION: Activation of S100A8/TLR4 signalling was
      elucidated in an animal model of diabetic glomerular injury accompanied with
      hyperlipidaemia, which may provide novel therapeutic targets in progressive
      diabetic nephropathy.

PMID- 22610401
TI  - Worth the wait: type 1 diabetes prospective birth cohort studies enter
      adolescence.
AB  - Autoantibodies to islet cell proteins currently provide the only reliable
      indication that the process leading to type 1 diabetes has started. The period
      from the first detection of islet autoantibodies to clinical onset of diabetes
      can last months or years. Longitudinal birth cohort family studies give crucial
      information concerning the natural history of islet autoimmunity and have already
      shown that islet autoantibodies, which precede diabetes development, often appear
      in early infancy. In this issue of Diabetologia, Ziegler et al (DOI:
      10.1007/s00125-012-2472-x ) and Parikka et al (DOI: 10.1007/s00125-012-2523-3 )
      report findings from their birth cohort studies after numerous children have
      entered adolescence, allowing a more complete picture of islet autoimmunity in
      childhood to be revealed. Both groups are in accord that, between 6 months and 3
      years of age, there is an explosion of islet autoimmunity in susceptible children
      and that the great majority (approximately 80%) of genetically at-risk children
      who present with diabetes before adolescence develop islet autoimmunity at this
      young age. These findings emphasise the importance of early life events in
      disease pathogenesis and have major implications for efforts aimed at preventing
      type 1 diabetes.

PMID- 22610402
TI  - Can bridge to recovery help to reveal the secrets of the failing heart?
AB  - Despite several decades of research and clinical experience, the basic mechanisms
      of the failing heart remain largely a secret. While pharmacological therapy can
      induce limited reverse remodeling, left ventricular assist device (LVAD) therapy
      offers the opportunity to induce significant improvements to the structure and
      function of the heart, with major clinical implications. LVAD therapy also
      provides significant insight into which changes have an impact on function and
      which do not, and could therefore reveal some of the secrets of the failing
      heart. In addition, LVAD-induced mechanical unloading may unlock further
      myocardial properties hitherto unknown such as the proliferation of the stem cell
      compartment. It may also serve as an important platform for emerging therapies
      such as gene and cell therapies. In this review, we highlight the most recent
      novel discoveries related to LVAD therapy and bridge to recovery (BTR).
      Discovering the integrated network of events that underlies BTR could unravel the
      secrets of the failing heart.

PMID- 22610403
TI  - PINK1 as a molecular checkpoint in the maintenance of mitochondrial function and
      integrity.
AB  - Parkinson's disease (PD), the most prevalent neurodegenerative movement disorder,
      is characterized by an age-dependent selective loss of dopaminergic (DA) neurons.
      Although most PD cases are sporadic, more than 20 responsible genes in familial
      cases were identified recently. Genetic studies using Drosophila models
      demonstrate that PINK1, a mitochondrial kinase encoded by a PD-linked gene PINK1,
      is critical for maintaining mitochondrial function and integrity. This suggests
      that mitochondrial dysfunction is the main cause of PD pathogenesis. Further
      genetic and cell biological studies revealed that PINK1 recruits Parkin, an E3
      ubiquitin ligase encoded by another PD-linked gene parkin, to mitochondria and
      regulates the mitochondrial remodeling process via the Parkin-mediated
      ubiquitination of various mitochondrial proteins. PINK1 also directly
      phosphorylates the mitochondrial proteins Miro and TRAP1, subsequently inhibiting
      mitochondrial transport and mitochondrial oxidative damage, respectively.
      Moreover, recent Drosophila genetic analyses demonstrate that the neuroprotective
      molecules Sir2 and FOXO specifically complement mitochondrial dysfunction and DA
      neuron loss in PINK1 null mutants, suggesting that Sir2 and FOXO protect
      mitochondria and DA neurons downstream of PINK1. Collectively, these recent
      results suggest that PINK1 plays multiple roles in mitochondrial quality control
      by regulating its mitochondrial, cytosolic, and nuclear targets.

PMID- 22610404
TI  - Differentiated embryo chondrocyte 1 (DEC1) represses PPARgamma2 gene through
      interacting with CCAAT/enhancer binding protein beta (C/EBPbeta).
AB  - DEC1 is a transcription repressor that is induced by Hypoxia-Inducible Factor
      alpha/beta (HIF-alpha/beta). In this study, we found that either hypoxic
      treatment or ectopic expression of DEC1 blocks induction of a master adipogenic
      transactivator, peroxisome proliferative activated receptor-gamma2 (PPARgamma2)
      in 3T3-L1 cells. DEC1 did not prevent C/EBPbeta, which is an upstream
      transactivator for PPARgamma2, from occupying the PPARgamma2 promoter. DEC1
      occupied the PPARgamma2 promoter by interacting with DNA-bound C/EBPbeta. DEC1
      occupancy was accompanied by a reduction of acetylated histones and an increase
      in histone deacetylase 1 (HDAC1) occupancy on the PPARgamma2 promoter. Based on
      the fact that DEC1 interacts with HDAC1, this study suggests that DEC1 blocks
      adipogenesis by reinforcing HDAC1 recruitment to the PPARgamma2 promoter. This
      study implies that DEC1 is one of the mediators that reset the pattern of
      PPARgamma2 expression in response to hypoxia.

PMID- 22610406
TI  - Chromatin loop formation in the beta-globin locus and its role in globin gene
      transcription.
AB  - Although linearly distant along mouse chromosome 7 and human chromosome 11, the
      mammalian beta-globin gene is located in close proximity to the upstream locus
      control region enhancer when it is actively transcribed in the nuclear chromatin
      environment of erythroid cells. This organization is thought to generate a
      chromatin loop between the LCR, a powerful enhancer, and active globin genes by
      extruding intervening regions containing inactive genes. Loop formation in the
      beta-globin locus requires erythroid specific transcriptional activators, co
      factors and insulator-related factors. Chromatin structural features such as
      histone modifications and DNase I hypersensitive site formation as well as
      nuclear localization are all involved in loop formation in the locus through
      diverse mechanisms. Current models envision the formation of the loop as a
      necessary step in globin gene transcription activation, but this has not been
      definitively established and many questions remain about what is necessary to
      achieve globin gene transcription activation.

PMID- 22610405
TI  - Hyaluronic acid promotes angiogenesis by inducing RHAMM-TGFbeta receptor
      interaction via CD44-PKCdelta.
AB  - Hyaluronic acid (HA) has been shown to promote angiogenesis. However, the
      mechanism behind this effect remains largely unknown. Therefore, in this study,
      the mechanism of HA-induced angiogenesis was examined. CD44 and PKCdelta were
      shown to be necessary for induction of the receptor for HA-mediated cell motility
      (RHAMM), a HA-binding protein. RHAMM was necessary for HA-promoted cellular
      invasion and endothelial cell tube formation. Cytokine arrays showed that HA
      induced the expression of plasminogen activator-inhibitor-1 (PAI), a downstream
      target of TGFbeta receptor signaling. The induction of PAI-1 was dependent on
      CD44 and PKCdelta. HA also induced an interaction between RHAMM and TGFbeta
      receptor I, and induction of PAI-1 was dependent on RHAMM and TGFbeta receptor I.
      Histone deacetylase 3 (HDAC3), which is decreased by HA via rac1, reduced
      induction of plasminogen activator inhibitor-1 (PAI-1) by HA. ERK, which
      interacts with RHAMM, was necessary for induction of PAI-1 by HA. Snail, a
      downstream target of TGFbeta signaling, was also necessary for induction of PAI
      1. The down regulation of PAI-1 prevented HA from enhancing endothelial cell tube
      formation and from inducing expression of angiogenic factors, such as ICAM-1,
      VCAM-1 and MMP-2. HDAC3 also exerted reduced expression of MMP-2. In this study,
      we provide a novel mechanism of HA-promoted angiogenesis, which involved RHAMM
      TGFbetaRI signaling necessary for induction of PAI-1.

PMID- 22610421
TI  - Unprotected sex of homeless youth: results from a multilevel dyadic analysis of
      individual, social network, and relationship factors.
AB  - Homeless youth have elevated risk of HIV through sexual behavior. This project
      investigates the multiple levels of influence on unprotected sex among homeless
      youth, including social network, individual, and partner level influences.
      Findings are based on analyses of an exploratory, semi-structured interview (n =
      40) and a structured personal network interview (n = 240) with randomly selected
      homeless youth in Los Angeles. Previous social network studies of risky sex by
      homeless youth have collected limited social network data from non-random samples
      and have not distinguished sex partner influences from other network influences.
      The present analyses have identified significant associations with unprotected
      sex at multiple levels, including individual, partner, and, to a lesser extent,
      the social network. Analyses also distinguished between youth who did or did not
      want to use condoms when they had unprotected sex. Implications for social
      network based HIV risk interventions with homeless youth are discussed.

PMID- 22610422
TI  - Strategies for optimizing clinic efficiency in a community-based antiretroviral
      treatment programme in Uganda.
AB  - We address a critical aspect of antiretroviral therapy (ART) scale-up: poor
      clinic organization leading to long waiting times and reduced patient retention.
      Using a before and after study design, time and motion studies and qualitative
      methods we evaluated the impact of triage and longer clinic appointment intervals
      (triage) on clinic efficiency in a community-based program in Uganda. We compared
      time waiting to see and time spent with providers for various patient categories
      and examined patient and provider satisfaction with the triage. Overall, median
      time spent at the clinic reduced from 206 to 83 min. Total median time waiting to
      see providers for stable-ART patients reduced from 102 to 20 min while that for
      patients undergoing ART preparation reduced 88-37 min. Improved patient flow,
      patient and provider satisfaction and reduced waiting times allowed for service
      delivery to more patients using the same staff following the implementation of
      triage.

PMID- 22610423
TI  - Flexible protein docking refinement using pose-dependent normal mode analysis.
AB  - Modeling conformational changes in protein docking calculations is challenging.
      To make the calculations tractable, most current docking algorithms typically
      treat proteins as rigid bodies and use soft scoring functions that implicitly
      accommodate some degree of flexibility. Alternatively, ensembles of structures
      generated from molecular dynamics (MD) may be cross-docked. However, such
      combinatorial approaches can produce many thousands or even millions of docking
      poses, and require fast and sensitive scoring functions to distinguish them.
      Here, we present a novel approach called "EigenHex," which is based on normal
      mode analyses (NMAs) of a simple elastic network model of protein flexibility. We
      initially assume that the proteins to be docked are rigid, and we begin by
      performing conventional soft docking using the Hex polar Fourier correlation
      algorithm. We then apply a pose-dependent NMA to each of the top 1000 rigid body
      docking solutions, and we sample and re-score multiple perturbed docking
      conformations generated from linear combinations of up to 20 eigenvectors using a
      multi-threaded particle swarm optimization algorithm. When applied to the 63
      "rigid body" targets of the Protein Docking Benchmark version 2.0, our results
      show that sampling and re-scoring from just one to three eigenvectors gives a
      modest but consistent improvement for these targets. Thus, pose-dependent NMA
      avoids the need to sample multiple eigenvectors and it offers a promising
      alternative to combinatorial cross-docking.

PMID- 22610425
TI  - Development of an efficient in vivo system (Pjunc-TpaseIS1223) for random
      transposon mutagenesis of Lactobacillus casei.
AB  - The random transposon mutagenesis system P(junc)-TpaseIS(1223) is composed of
      plasmids pVI129, expressing IS1223 transposase, and pVI110, a suicide transposon
      plasmid carrying the P(junc) sequence, the substrate of the IS1223 transposase.
      This system is particularly efficient in Lactobacillus casei, as more than 10,000
      stable, random mutants were routinely obtained via electroporation.

PMID- 22610424
TI  - Genome sequence of thermotolerant Bacillus methanolicus: features and regulation
      related to methylotrophy and production of L-lysine and L-glutamate from
      methanol.
AB  - Bacillus methanolicus can utilize methanol as its sole carbon and energy source,
      and the scientific interest in this thermotolerant bacterium has focused largely
      on exploring its potential as a biocatalyst for the conversion of methanol into L
      lysine and L-glutamate. We present here the genome sequences of the important B.
      methanolicus model strain MGA3 (ATCC 53907) and the alternative wild-type strain
      PB1 (NCIMB13113). The physiological diversity of these two strains was
      demonstrated by a comparative fed-batch methanol cultivation displaying highly
      different methanol consumption and respiration profiles, as well as major
      differences in their L-glutamate production levels (406 mmol liter(-1) and 11
      mmol liter(-1), respectively). Both genomes are small (ca 3.4 Mbp) compared to
      those of other related bacilli, and MGA3 has two plasmids (pBM19 and pBM69),
      while PB1 has only one (pBM20). In particular, we focus here on genes
      representing biochemical pathways for methanol oxidation and concomitant
      formaldehyde assimilation and dissimilation, the important phosphoenol
      pyruvate/pyruvate anaplerotic node, the tricarboxylic acid cycle including the
      glyoxylate pathway, and the biosynthetic pathways for L-lysine and L-glutamate.
      Several unique findings were made, including the discovery of three different
      methanol dehydrogenase genes in each of the two B. methanolicus strains, and the
      genomic analyses were accompanied by gene expression studies. Our results provide
      new insight into a number of peculiar physiological and metabolic traits of B.
      methanolicus and open up possibilities for system-level metabolic engineering of
      this bacterium for the production of amino acids and other useful compounds from
      methanol.

PMID- 22610426
TI  - Decreased toxicity of Bacillus thuringiensis subsp. israelensis to mosquito
      larvae after contact with leaf litter.
AB  - Bacillus thuringiensis subsp. israelensis is a bacterium producing crystals
      containing Cry and Cyt proteins, which are toxic for mosquito larvae. Nothing is
      known about the interaction between crystal toxins and decaying leaf litter,
      which is a major component of several mosquito breeding sites and represents an
      important food source. In the present work, we investigated the behavior of B.
      thuringiensis subsp. israelensis toxic crystals sprayed on leaf litter. In the
      presence of leaf litter, a 60% decrease in the amount of Cyt toxin detectable by
      immunology (enzyme-linked immunosorbent assays [ELISAs]) was observed, while the
      respective proportions of Cry toxins were not affected. The toxicity of Cry
      toxins toward Aedes aegypti larvae was not affected by leaf litter, while the
      synergistic effect of Cyt toxins on all B. thuringiensis subsp. israelensis Cry
      toxins was decreased by about 20% when mixed with leaf litter. The toxicity of
      two commercial B. thuringiensis subsp. israelensis strains (VectoBac WG and
      VectoBac 12AS) and a laboratory-produced B. thuringiensis subsp. israelensis
      strain decreased by about 70% when mixed with leaf litter. Taken together, these
      results suggest that Cyt toxins interact with leaf litter, resulting in a
      decreased toxicity of B. thuringiensis subsp. israelensis in litter-rich
      environments and thereby dramatically reducing the efficiency of mosquitocidal
      treatments.

PMID- 22610427
TI  - A gain-of-function mutation in gating of Corynebacterium glutamicum NCgl1221
      causes constitutive glutamate secretion.
AB  - The A-to-V mutation at position 111 (A111V) in the mechanosensitive channel
      NCgl1221 (MscCG) causes constitutive glutamate secretion in Corynebacterium
      glutamicum. Patch clamp experiments revealed that NCgl1221 (A111V) had a
      significantly smaller gating threshold than the wild-type counterpart and
      displayed strong hysteresis, suggesting that the gain-of-function mutation in the
      gating of NCgl1221 leads to the oversecretion of glutamate.

PMID- 22610428
TI  - Microbial quality of tropical inland waters and effects of rainfall events.
AB  - Novel markers of fecal pollution in tropical waters are needed since conventional
      methods recommended for other geographical regions may not apply. To address
      this, the prevalence of thermotolerant coliforms, enterococci, coliphages, and
      enterophages was determined by culture methods across a watershed. Additionally,
      human-, chicken-, and cattle-specific PCR assays were used to identify potential
      fecal pollution sources in this watershed. An enterococcus quantitative PCR
      (qPCR) assay was tested and correlated with culture methods at three sites since
      water quality guidelines could incorporate this technique as a rapid detection
      method. Various rainfall events reported before sample collection at three sites
      were considered in the data analyses. Thermotolerant coliforms, enterococci,
      coliphages, and enterophages were detected across the watershed. Human-specific
      Bacteroides bacteria, unlike the cattle- and chicken-specific bacteria, were
      detected mostly at sites with the corresponding fecal impact. Enterococci were
      detected by qPCR as well, but positive correlations with the culture method were
      noted at two sites, suggesting that either technique could be used. However, no
      positive correlations were noted for an inland lake tested, suggesting that qPCR
      may not be suitable for all water bodies. Concentrations of thermotolerant
      coliforms and bacteriophages were consistently lower after rainfall events,
      pointing to a possible dilution effect. Rainfall positively correlated with
      enterococci detected by culturing and qPCR, but this was not the case for the
      inland lake. The toolbox of methods and correlations presented here could be
      potentially applied to assess the microbial quality of various water types.

PMID- 22610429
TI  - Influence of adhesion and bacteriocin production by Lactobacillus salivarius on
      the intestinal epithelial cell transcriptional response.
AB  - Lactobacillus salivarius strain UCC118 is a human intestinal isolate that has
      been extensively studied for its potential probiotic effects in human and animal
      models. The objective of this study was to determine the effect of L. salivarius
      UCC118 on gene expression responses in the Caco-2 cell line to improve
      understanding of how the strain might modulate intestinal epithelial cell
      phenotypes. Exposure of Caco-2 cells to UCC118 led to the induction of several
      human genes (TNFAIP3, NFKBIA, and BIRC3) that are negative regulators of
      inflammatory signaling pathways. Induction of chemokines (CCL20, CXCL-1, and CXCL
      2) with antimicrobial functions was also observed. Disruption of the UCC118
      sortase gene srtA causes reduced bacterial adhesion to epithelial cells.
      Transcription of three mucin genes was reduced significantly when Caco-2 cells
      were stimulated with the DeltasrtA derivative of UCC118 compared to cells
      stimulated with the wild type, but there was no significant change in the
      transcription levels of the anti-inflammatory genes. UCC118 genes that were
      significantly upregulated upon exposure to Caco-2 cells were identified by
      bacterial genome microarray and consisted primarily of two groups of genes
      connected with purine metabolism and the operon for synthesis of the Abp118
      bacteriocin. Following incubation with Caco-2 cells, the bacteriocin synthesis
      genes were transcribed at higher levels in the wild type than in the DeltasrtA
      derivative. These data indicate that L. salivarius UCC118 influences epithelial
      cells both through modulation of the inflammatory response and by modulation of
      intestinal cell mucin production. Sortase-anchored cell surface proteins of L.
      salivarius UCC118 have a central role in promoting the interaction between the
      bacterium and epithelial cells.

PMID- 22610430
TI  - Gene cloning, purification, and characterization of a novel peptidoglutaminase
      asparaginase from Aspergillus sojae.
AB  - Glutaminase is an enzyme that catalyzes the hydrolysis of l-glutamine to l
      glutamate, and it plays an important role in the production of fermented foods by
      enhancing the umami taste. By using the genome sequence and expressed sequence
      tag data available for Aspergillus oryzae RIB40, we cloned a novel glutaminase
      gene (AsgahA) from Aspergillus sojae, which was similar to a previously described
      gene encoding a salt-tolerant, thermostable glutaminase of Cryptococcus nodaensis
      (CnGahA). The structural gene was 1,929 bp in length without introns and encoded
      a glutaminase, AsGahA, which shared 36% identity with CnGahA. The introduction of
      multiple copies of AsgahA into A. oryzae RIB40 resulted in the overexpression of
      glutaminase activity. AsGahA was subsequently purified from the overexpressing
      transformant and characterized. While AsGahA was located at the cell surface in
      submerged culture, it was secreted extracellularly in solid-state culture. The
      molecular mass of AsGahA was estimated to be 67 kDa and 135 kDa by SDS-PAGE and
      gel filtration chromatography, respectively, indicating that the native form of
      AsGahA was a dimer. The optimal pH of the enzyme was 9.5, and its optimal
      temperature was 50 degrees C in sodium phosphate buffer (pH 7.0). Analysis of
      substrate specificity revealed that AsGahA deamidated not only free l-glutamine
      and l-asparagine but also C-terminal glutaminyl or asparaginyl residues in
      peptides. Collectively, our results indicate that AsGahA is a novel
      peptidoglutaminase-asparaginase. Moreover, this is the first report to describe
      the gene cloning and purification of a peptidoglutaminase-asparaginase.

PMID- 22610431
TI  - Development of a tightly regulatable copper-mediated gene switch system in
      dermatophytes.
AB  - Targeted gene deletion is now available for molecular genetic research of
      dermatophytes, and the physiological roles of several genes have been elucidated.
      However, this method cannot be applied to essential genes, which can be potential
      drug targets. To overcome this limitation, we have developed a conditional gene
      knockdown system using a copper-responsive promoter. The promoter sequence of the
      copper transporter gene CTR4 (P(CTR4)) and that of the copper efflux pump gene
      CRP1 (P(CRP1)) derived from Trichophyton rubrum were examined for their response
      to copper in Arthroderma vanbreuseghemii. P(CTR4) was demonstrated to repress
      expression of a reporter gene in the presence of copper, while the activity of
      P(CRP1) was induced by addition of copper. Importantly, P(CTR4) regulated the
      gene expression more tightly. Furthermore, when P(CTR4) was applied to regulate
      the expression of the endogenous genes ERG1 and TRP5, their conditional mutants
      exhibited decreased growth activity under the repressive conditions. These
      results suggest that the P(CTR4)-based gene regulation system represents a
      powerful tool for identification and characterization of a broad range of genes,
      including essential genes, in dermatophytes.

PMID- 22610433
TI  - Relevance of Bacteroidales and F-specific RNA bacteriophages for efficient fecal
      contamination tracking at the level of a catchment in France.
AB  - The relevance of three host-associated Bacteroidales markers (HF183, Rum2Bac, and
      Pig2Bac) and four F-specific RNA bacteriophage genogroups (FRNAPH I to IV) as
      microbial source tracking markers was assessed at the level of a catchment
      (Daoulas, France). They were monitored together with fecal indicators
      (Escherichia coli and enterococci) and chemophysical parameters (rainfall,
      temperature, salinity, pH, and turbidity) by monthly sampling over 2 years (n =
      240 water samples) and one specific sampling following an accidental pig manure
      spillage (n = 5 samples). During the 2-year regular monitoring, levels of E.
      coli, enterococci, total F-specific RNA bacteriophages, and the general
      Bacteroidales marker AllBac were strongly correlated with one another and with
      Rum2Bac (r = 0.37 to 0.50, P < 0.0001). Their correlations with HF183 and FRNAPH
      I and II were lower (r = 0.21 to 0.29, P < 0.001 to P < 0.0001), and HF183 and
      enterococci were associated rather than correlated (Fisher's exact test, P <
      0.01). Rum2Bac and HF183 enabled 73% of water samples that had >= 2.7 log(10)
      most probably number (MPN) of E. coli/100 ml to be classified. FRNAPH I and II
      enabled 33% of samples at this contamination level to be classified. FRNAPH I and
      II complemented the water sample classification obtained with the two
      Bacteroidales markers by an additional 8%. Pig2Bac and FRNAPH III and IV were
      observed in a small number of samples (n = 0 to 4 of 245). The present study
      validates Rum2Bac and HF183 as relevant tools to trace fecal contamination
      originating from ruminant or human waste, respectively, at the level of a whole
      catchment.

PMID- 22610432
TI  - Influence of cofermentation by amylolytic Lactobacillus plantarum and Lactococcus
      lactis strains on the fermentation process and rheology of sorghum porridge.
AB  - Amylolytic lactic acid bacteria (ALAB) can potentially replace malt in reducing
      the viscosity of starchy porridges. However, the drawback of using ALAB is their
      low and delayed amylolytic activity. This necessitates searching for efficient
      ALAB and strategies to improve their amylolytic activity. Two ALAB, Lactobacillus
      plantarum MNC 21 and Lactococcus lactis MNC 24, isolated from Obushera, were used
      to ferment starches in MRS broth: sorghum, millet, sweet potato, and commercial
      soluble starch. The amylolytic activity of MNC 21 was comparable to that of the
      ALAB collection strain Lb. plantarum A6, while that of MNC 24 was extremely low.
      MNC 21, MNC 24, and their coculture were compared to A6 and sorghum malt for
      ability to ferment and reduce the viscosity of sorghum porridge (11.6% dry
      matter). ALAB and the coculture lowered the pH from 6.2 to <4.5 within 12 h,
      while malt as a carrier of wild starter took about 20 h. Coculturing increased
      lactic acid yield by 46% and 76.8% compared to the yields of MNC 21 and MNC 24
      monocultures, respectively. The coculture accumulated significantly larger (P <
      0.05) amounts of maltose and diacetyl than the monocultures. Sorghum malt control
      and the coculture hydrolyzed more starch in sorghum porridge than the
      monocultures. The coculture initiated changes in the rheological parameters
      storage modulus (G'), loss modulus (G"), phase angle (delta), and complex
      viscosity (eta*) earlier than its constituent monocultures. The shear viscosity
      of sorghum porridge was reduced significantly (P < 0.05) from 1950 cP to 110 cP
      (malt), 281 cP (coculture), 382 cP (MNC 21), 713 cP (MNC 24), and 722 cP (A6).
      Coculturing strong ALAB with weak ALAB or non-ALAB can be exploited for
      preparation of nutrient-dense weaning foods and increasing lactic acid yield from
      starchy materials.

PMID- 22610434
TI  - Expression of bacterial GshF in Pichia pastoris for glutathione production.
AB  - Conventionally, two consecutive enzymatic reactions catalyzed by gamma
      glutamylcysteine synthetase and glutathione synthetase are most commonly used for
      glutathione production. Here we demonstrate that bacterial bifunctional GshF can
      be used for glutathione production in a eukaryotic system without accumulation of
      the intermediate gamma-glutamylcysteine.

PMID- 22610435
TI  - Isolation of a gene responsible for the oxidation of trans-anethole to para
      anisaldehyde by Pseudomonas putida JYR-1 and its expression in Escherichia coli.
AB  - A plasmid, pTA163, in Escherichia coli contained an approximately 34-kb gene
      fragment from Pseudomonas putida JYR-1 that included the genes responsible for
      the metabolism of trans-anethole to protocatechuic acid. Three Tn5-disrupted open
      reading frame 10 (ORF 10) mutants of plasmid pTA163 lost their abilities to
      catalyze trans-anethole. Heterologously expressed ORF 10 (1,047 nucleotides [nt])
      under a T7 promoter in E. coli catalyzed oxidative cleavage of a propenyl group
      of trans-anethole to an aldehyde group, resulting in the production of para
      anisaldehyde, and this gene was designated tao (trans-anethole oxygenase). The
      deduced amino acid sequence of TAO had the highest identity (34%) to a
      hypothetical protein of Agrobacterium vitis S4 and likely contained a flavin
      binding site. Preferred incorporation of an oxygen molecule from water into p
      anisaldehyde using (18)O-labeling experiments indicated stereo preference of TAO
      for hydrolysis of the epoxide group. Interestingly, unlike the narrow substrate
      range of isoeugenol monooxygenase from Pseudomonas putida IE27 and Pseudomonas
      nitroreducens Jin1, TAO from P. putida JYR-1 catalyzed isoeugenol, O-methyl
      isoeugenol, and isosafrole, all of which contain the 2-propenyl functional group
      on the aromatic ring structure. Addition of NAD(P)H to the ultrafiltered cell
      extracts of E. coli (pTA163) increased the activity of TAO. Due to the relaxed
      substrate range of TAO, it may be utilized for the production of various
      fragrance compounds from plant phenylpropanoids in the future.

PMID- 22610436
TI  - Thermal inactivation of infectious hepatitis E virus in experimentally
      contaminated food.
AB  - Hepatitis E virus (HEV) infection of zoonotic origin is an emerging concern in
      industrialized countries. In the past few years, several cases of zoonotic
      hepatitis E have been identified and the consumption of food products derived
      from pork liver have been associated with clusters of human cases. More
      specifically, raw or undercooked pork products have been incriminated. Few data
      on the effect of heating on HEV inactivation in food products are available. In
      the present study, the various times and temperatures that are used during
      industrial processing of pork products were applied to experimentally
      contaminated food preparations. After treatment, the presence of residual
      infectious virus particles was investigated using real-time reverse transcription
      PCR and an in vivo experimental model in pigs. Results show that heating the food
      to an internal temperature of 71 degrees C for 20 min is necessary to completely
      inactivate HEV. These results are very important for determining processing
      methods to ensure food safety in regard to food-borne hepatitis E.

PMID- 22610437
TI  - The acyl homoserine lactone receptor, SdiA, of Escherichia coli and Salmonella
      enterica serovar Typhimurium does not respond to indole.
AB  - In this study, we tested the hypothesis that the SdiA proteins of Escherichia
      coli and Salmonella enterica serovar Typhimurium respond to indole. While indole
      was found to have effects on gene expression and biofilm formation, these effects
      were not sdiA dependent. However, high concentrations of indole did inhibit N
      acyl-l-homoserine lactone (AHL) sensing by SdiA. We conclude that SdiA does not
      respond to indole but indole can inhibit SdiA activity in E. coli and Salmonella.

PMID- 22610438
TI  - Enrichment of microbial electrolysis cell biocathodes from sediment microbial
      fuel cell bioanodes.
AB  - Electron-accepting (electrotrophic) biocathodes were produced by first enriching
      graphite fiber brush electrodes as the anodes in sediment-type microbial fuel
      cells (sMFCs) using two different marine sediments and then electrically
      inverting the anodes to function as cathodes in two-chamber bioelectrochemical
      systems (BESs). Electron consumption occurred at set potentials of -439 mV and 
      539 mV (versus the potential of a standard hydrogen electrode) but not at -339 mV
      in minimal media lacking organic sources of energy. Results at these different
      potentials were consistent with separate linear sweep voltammetry (LSV) scans
      that indicated enhanced activity (current consumption) below only ca. -400 mV.
      MFC bioanodes not originally acclimated at a set potential produced electron
      accepting (electrotrophic) biocathodes, but bioanodes operated at a set potential
      (+11 mV) did not. CO(2) was removed from cathode headspace, indicating that the
      electrotrophic biocathodes were autotrophic. Hydrogen gas generation, followed by
      loss of hydrogen gas and methane production in one sample, suggested
      hydrogenotrophic methanogenesis. There was abundant microbial growth in the
      biocathode chamber, as evidenced by an increase in turbidity and the presence of
      microorganisms on the cathode surface. Clone library analysis of 16S rRNA genes
      indicated prominent sequences most similar to those of Eubacterium limosum
      (Butyribacterium methylotrophicum), Desulfovibrio sp. A2, Rhodococcus opacus, and
      Gemmata obscuriglobus. Transfer of the suspension to sterile cathodes made of
      graphite plates, carbon rods, or carbon brushes in new BESs resulted in enhanced
      current after 4 days, demonstrating growth by these microbial communities on a
      variety of cathode substrates. This report provides a simple and effective method
      for enriching autotrophic electrotrophs by the use of sMFCs without the need for
      set potentials, followed by the use of potentials more negative than -400 mV.

PMID- 22610439
TI  - One-step sequence- and ligation-independent cloning as a rapid and versatile
      cloning method for functional genomics studies.
AB  - We developed one-step sequence- and ligation-independent cloning (SLIC) as a
      simple, cost-effective, time-saving, and versatile cloning method. Highly
      efficient and directional cloning can be achieved by direct bacterial
      transformation 2.5 min after mixing any linearized vector, an insert(s) prepared
      by PCR, and T4 DNA polymerase in a tube at room temperature.

PMID- 22610440
TI  - Asymptomatic thoracic Pantopaque cyst mimicking an intradural extramedullary
      lipoma on MR images.
AB  - OBJECTIVE: Oil-based contrast media such as Pantopaque have not used for imaging
      for several decades, but because these contrast media have an extremely low
      clearance rate, the remnant contrast media or residual sequelae of these
      materials may be encountered in the clinical field. CLINICAL PRESENTATION: A 63
      year-old woman presented to our hospital complaining of increasing lower back
      pain and lower extremity paresthesia with incontinence for 2 years. A plain X-ray
      film revealed single droplet-like mass at the lower thoracic T9-T10. A magnetic
      resonance image (MRI) study revealed a dorsally placed extramedullary intradural
      lesion, compressing the thoracic cord and minimally displacing it anteriorly.
      Spinal stenosis was also noted at the L4-5 level. INTERVENTION: The patient was
      performed for two consecutive surgeries. Total laminectomy was performed at T9
      T10 to remove mass. A 0.5 * 0.5 * 4 cm yellowish intradural extramedullary cystic
      mass was removed without any leakage of cystic contents. Partial hemi-laminectomy
      and foraminotomy was then done at L4-5 levels for radiculopathy symptom relief.
      The fluid from the cyst was composed mainly of iodide. CONCLUSION: Intraspinal
      masses showing metal-like density in X-ray or computed tomography but in MRI
      showing only lipoma or cystic lesions, not metallic characteristics, the
      differential diagnosis should include iophendylate (Pantopaque) cyst. Oil-based
      contrast medium is believed to have the potential to make a syrinx formation via
      arachnoiditis, which can lead to severe neurologic deteriorations, so even if the
      patients do not represent with an acute neurologic deficit, surgical total
      removal of remnant material without leaking should be considered.

PMID- 22610441
TI  - Late infections after dynamic stabilization of the lumbar spine with Dynesys.
AB  - INTRODUCTION: Dynamic stabilization of the spine was developed as an alternative
      to rigid fusion in chronic back pain to reduce the risk of adjacent segment
      degeneration. Dynamic neutralization system (Dynesys, Zimmer CH) is one of the
      most popular systems available, but some midterm studies show revision rates as
      high as 30 %. Some late infectious complications in our patients prompted us to
      review them systematically. Propionibacterium recently has been shown to cause
      subtle infections of prosthetic material. MATERIALS AND METHODS: Here, we report
      on a consecutive series of 50 Dynesys implants. In a median follow-up of 51
      months (range 0-91), we identified 12 infectious and 11 non-infectious
      complications necessitating reoperation or removal of the implant in 17 patients.
      RESULTS: Material infections occurred after a median of 52 months (2-77) and were
      due to Propionibacterium alone (n = 4) or in combination (n = 3) in seven out of
      11 patients. Clinical presentation combines new or increasing pain associated
      with signs of screw loosening on conventional X-rays; however, as many as 73.5 %
      of patients present some degree of screw loosening without being at all
      symptomatic of infection. CONCLUSION: The high rate of late infections with low
      grade germs and the frequency of screw loosening signs made us suspect a lack of
      integration at the bone-screw interface. Surgeons should be suspicious if the
      patient presents a combination of new or increasing pain and signs of screw
      loosening, and aggressive revision is recommended in these cases.

PMID- 22610442
TI  - Parameters of lengthened sacroiliac screw fixation: a radiological anatomy study.
AB  - OBJECTIVE: To provide the anatomical basis for the feasibility and clinical
      practice of lengthened sacroiliac screw fixation, by measuring various related
      indicators of the safe insertion regions of S1 and S2 lengthened sacroiliac
      screws. METHODS: A total of 66 healthy pelvises of adults were scanned by 64
      slice spiral CT and the length, width and height of the safe insertion regions
      for S1 and S2 lengthened sacroiliac screw were measured. The safe screw entrance
      point locations were described with a quantitative method. The indicators were
      recorded by descriptive statistics and the statistics of left and right sides,
      segments of S1 and S2, and different layers (including top, middle and bottom
      parts) of S1 and S2 were compared. RESULTS: The lengths of ilium within the safe
      insertion regions for lengthened screws are more than 16 mm. The width and height
      of the safe insertion region of S1 and S2 are almost all more than 7.3 mm.
      Generally, the width and height of S1 are larger than those of S2. The reference
      ranges of the best/safest entrance point locations of lengthened sacroiliac
      screws are as follows-S1: 42.21-63.69 mm in front of posterior superior iliac
      spine, 32.77-53.75 mm above the highest point of the greater sciatic notch; S2:
      22.68-54.28 mm in front of posterior superior iliac spine, 14.06-33.70 mm above
      the highest point of the greater sciatic notch. CONCLUSION: (1) There is
      anatomical feasibility for the placements of S1 and S2 lengthened sacroiliac
      screws. (2) phi 7.3-mm partial thread cannulated screw (thread length 16 mm) and
      phi 6.5-mm partial thread cancellous screw(thread length 16 mm) can be used as
      lengthened sacroiliac lag screw. (3) The safe insertion space of S1 is larger
      than that of S2. (4) There is safe space for placement of at least one piece of
      lengthened sacroiliac screw in both S1 and S2. (5) The best/safest entrance
      points of S1 and S2 can be approximately located with anatomical landmarks.

PMID- 22610443
TI  - Septal localization of the Mycobacterium tuberculosis MtrB sensor kinase promotes
      MtrA regulon expression.
AB  - The mechanisms responsible for activation of the MtrAB two-component regulatory
      signal transduction system, which includes sensor kinase MtrB and response
      regulator MtrA, are unknown. Here, we show that an MtrB-GFP fusion protein
      localized to the cell membrane, the septa, and the poles in Mycobacterium
      tuberculosis and Mycobacterium smegmatis. This localization was independent of
      MtrB phosphorylation status but dependent upon the assembly of FtsZ, the
      initiator of cell division. The M. smegmatis mtrB mutant was filamentous,
      defective for cell division, and contained lysozyme-sensitive cell walls. The
      mtrB phenotype was complemented by either production of MtrB protein competent
      for phosphorylation or overproduction of MtrA(Y102C) and MtrA(D13A) mutant
      proteins exhibiting altered phosphorylation potential, indicating that either
      MtrB phosphorylation or MtrB independent expression of MtrA regulon genes,
      including those involved in cell wall processing, are necessary for regulated
      cell division. In partial support of this observation, we found that the
      essential cell wall hydrolase ripA is an MtrA target and that the expression of
      bona fide MtrA targets ripA, fbpB, and dnaA were compromised in the mtrB mutant
      and partially rescued upon MtrA(Y102C) and MtrA(D13A) overproduction. MtrB septal
      assembly was compromised upon FtsZ depletion and exposure of cells to mitomycin
      C, a DNA damaging agent, which interferes with FtsZ ring assembly. Expression of
      MtrA targets was also compromised under the above conditions, indicating that
      MtrB septal localization and MtrA regulon expression are linked. We propose that
      MtrB septal association is a necessary feature of MtrB activation that promotes
      MtrA phosphorylation and MtrA regulon expression.

PMID- 22610444
TI  - Monitoring bluetongue virus vectors in Andalusia (SW Europe): Culicoides species
      composition and factors affecting capture rates of the biting midge Culicoides
      imicola.
AB  - In this work, we summarize the results of captures of Culicoides species in
      Andalusia (S Spain) during 2007-2008. Four out of the 15 midge species-Culicoides
      imicola, Culicoides obsoletus complex, Culicoides pulicaris complex, and
      Culicoides nubeculosus-accounted for 80.7 % of captures (n = 68,190). Captures
      were seasonal and mostly occurred in May-November. The overall number of
      Culicoides specimens captured and the mean number of caught per trap were higher
      in 2007. We used an information-theoretic approach to analyze whether
      environmental factors (e.g., weather, altitude above the sea level, distance of
      the trap from the ground, distance to animals, and land use) affected C. imicola
      capture probability and success. Mean temperature and rainfall (both integrated
      into the Gaussen index), distance of traps to host animals, and trap height above
      the ground were the main factors explaining variance in capture rates in the
      Bluetongue Entomologic Surveillance Andalusian Program (BESAP). However, all of
      these patterns strongly varied among traps. As previously remarked by other
      authors, standardized capture methods and protocols for trap use are needed to
      ensure that results obtained in different geographical areas and/or periods are
      comparable.

PMID- 22610445
TI  - Central nervous system of Rhipicephalus sanguineus ticks (Acari: Ixodidae): an
      ultrastructural study.
AB  - This study performed the ultrastructural description of the synganglion of
      Rhipicephalus sanguineus males and females, aiming to contribute to the
      understanding of the cellular organization of this organ. The results show that
      the central nervous system of these individuals consists of a mass of fused
      nerves, named synganglion, from where nerves emerge towards several parts of the
      body. It is surrounded by the neural lamella, a uniform and acellular layer,
      constituted by repeated layers of homogeneous and finely granular material. The
      perineurium is just below, composed of glial cells, which extensions invaginate
      throughout the nervous tissue. The synganglion is internally divided into an
      outer cortex, which contains the cellular bodies of the neural cells and an inner
      neuropile. The neural cells can be classified into two types according to cell
      size, cytoplasm-nucleus relation, and neurosecretory activity. Type I cells are
      oval or spherical and present a large nucleus occupying most part of the
      cytoplasm, which contains few organelles. Type 2 cells are polygonal, present a
      great cytoplasm volume, and their nuclei are located in the cell periphery. The
      cytoplasm of these cells contains a well-developed rough endoplasmic reticulum,
      Golgi regions, mitochondria, and several neurosecretory granules. The
      subperineurium and the tracheal ramifications are found between the cortex and
      the neuropile. The latter is formed mainly by neural fibers, tracheal elements,
      and glial cells. The results obtained show that R. sanguineus males' and females'
      nervous tissue present an ultrastructural organization similar to the one
      described in the literature for other tick species.

PMID- 22610446
TI  - The painstaking discovery of the hidden face of the human plasmodia.
AB  - The difficulties encountered in the discovery of the exoerythrocytic stage of
      asexual cycle of human plasmodia are described. These illustrate how deference
      towards scientific orthodoxy and a degree of reluctance to question and to
      criticise can delay advances in knowledge.

PMID- 22610448
TI  - Nutritional status and complications in children with diabetic ketoacidosis.
AB  - OBJECTIVE: Diabetic ketoacidosis in children continues to be an important cause
      of morbidity and mortality, especially in developing economies as a result of
      malnutrition, a high rate of infections, and delay in seeking timely medical
      care. Malnutrition also increases the risk of diabetic ketoacidosis-related
      complications. The objective of this study was to assess the nutritional status
      of patients presenting with diabetic ketoacidosis and correlate it with the
      incidence of complications at presentation and those encountered during the
      course of illness. DESIGN: Prospective study. SETTING: Pediatric emergency and
      intensive care units, Advanced Pediatrics Centre, PGIMER, Chandigarh, India.
      PATIENTS: Thirty-three children between 1 month and 12 yrs of age presenting with
      diabetic ketoacidosis between July 2008 and June 2009 were enrolled consecutively
      and assessed for nutritional status by anthropometric parameters (body weight,
      crown-heel length/height, mid-upper arm circumference, triceps and subscapular
      skin fold thicknesses), biochemical parameters (serum albumin, zinc, magnesium,
      vitamin A levels), and preillness dietary history (by pretested Food Frequency
      Questionnaire). Patients were classified as malnourished or normally nourished
      based on the weight for age criteria matched for Indian standards. The incidence
      of complications (electrolyte imbalances, hypoglycemia, sepsis, cerebral edema,
      etc.) and outcome in terms of survival or death in both the groups were compared
      with Student's t-test for parametric data, Mann-Whitney U test for nonparametric
      data, and chi-square test for categorical variables. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Anthropometric assessment showed that 11 of 33
      (33.3%) were malnourished. Preillness dietary history revealed that 16 (48.5%)
      were calorie- and protein-deficient (known diabetic n = 7; new onset n = 9),
      whereas 11 (33.3%) were only calorie-deficient (known diabetic n = 2).
      Hypoalbuminemia was seen in 21 (63.6%), hypovitaminosis A in eight (24.2%), and
      low zinc levels in three (9%). The malnourished and normally nourished groups
      were similar with respect to demographics, precipitating factors, severity of
      diabetic ketoacidosis, treatment received, and outcome. However, the incidence
      and severity of therapy-related hypokalemia (100% vs. 72.7%; p = .05) and
      hypoglycemia (63.6 vs. 13.6%; p = .004) were significantly higher in the former
      as compared with the latter. The mean +/- SD admission serum potassium levels
      were similar in both the groups (3.4 +/- 0.8 mEq/L in the malnourished vs. 3.5 +/
      0.7 mEq/L in the normally nourished) with the malnourished group showing a
      significant fall at 6 hrs after start the of diabetic ketoacidosis protocol (2.8
      +/- 0.8 mEq/L vs. 3.6 +/- 0.7 mEq/L; p = .033), although the mean rate and dose
      of insulin infusion were similar. The fall in blood glucose (mean +/- SD mg/dL)
      at 12, 24, and 36 hrs after onset of the diabetic ketoacidosis protocol was also
      significantly greater in the malnourished group as compared with the normally
      nourished diabetic ketoacidosis (195 +/- 69.1 and 272.61 +/- 96.3, p = .02; 171
      +/- 58.5 and 257 +/- 96.3, p = .05; and 153.75 +/- 49.6 and 241.71 +/- 76.3, p =
      .04, respectively). The incidence of hypophosphatemia, hypomagnesemia, cerebral
      edema, renal failure, sepsis, and septic shock was similar in both the groups.
      There were two deaths, both resulting from complicating cerebral edema and renal
      failure and unrelated to the nutritional status of the patients. CONCLUSIONS: The
      incidence and severity of therapy-related hypokalemia and hypoglycemia were
      significantly higher in the malnourished as compared to the normally nourished
      diabetic ketoacidosis. Other diabetic ketoacidosis-related complications and
      outcome were similar in both the groups.

PMID- 22610447
TI  - The spectral networks paradigm in high throughput mass spectrometry.
AB  - High-throughput proteomics is made possible by a combination of modern mass
      spectrometry instruments capable of generating many millions of tandem mass
      (MS(2)) spectra on a daily basis and the increasingly sophisticated associated
      software for their automated identification. Despite the growing accumulation of
      collections of identified spectra and the regular generation of MS(2) data from
      related peptides, the mainstream approach for peptide identification is still the
      nearly two decades old approach of matching one MS(2) spectrum at a time against
      a database of protein sequences. Moreover, database search tools overwhelmingly
      continue to require that users guess in advance a small set of 4-6 post
      translational modifications that may be present in their data in order to avoid
      incurring substantial false positive and negative rates. The spectral networks
      paradigm for analysis of MS(2) spectra differs from the mainstream database
      search paradigm in three fundamental ways. First, spectral networks are based on
      matching spectra against other spectra instead of against protein sequences.
      Second, spectral networks find spectra from related peptides even before
      considering their possible identifications. Third, spectral networks determine
      consensus identifications from sets of spectra from related peptides instead of
      separately attempting to identify one spectrum at a time. Even though spectral
      networks algorithms are still in their infancy, they have already delivered the
      longest and most accurate de novo sequences to date, revealed a new route for the
      discovery of unexpected post-translational modifications and highly-modified
      peptides, enabled automated sequencing of cyclic non-ribosomal peptides with
      unknown amino acids and are now defining a novel approach for mapping the entire
      molecular output of biological systems that is suitable for analysis with tandem
      mass spectrometry. Here we review the current state of spectral networks
      algorithms and discuss possible future directions for automated interpretation of
      spectra from any class of molecules.

PMID- 22610449
TI  - Large choroidal melanoma diagnosed after cataract surgery.
AB  - A dense cataract prevents detailed fundus examination which may lead to delayed
      diagnosis of undiscovered intraocular pathology before cataract surgery. We
      report two cases where large choroidal melanomas were diagnosed after cataract
      surgery and/or Nd:Yag laser capsulotomy. In the first case, a dense cataract
      prevented proper examination of the fundus of an 84-year-old female. A brownish
      choroidal lesion was seen after cataract surgery and diagnosed as postoperative
      choroidal detachment. As this lesion persisted over months, the patient was sent
      to our hospital for evaluation where a diagnosis of choroidal melanoma with
      extrascleral growth was made and an enucleation with implantation of a dermis-fat
      graft was performed without complication 10 days later. In the second case, a 58
      year-old female patient had Nd:Yag laser treatment 2 years after cataract surgery
      had been performed. During fundus examination 1 day after treatment, the
      ophthalmologist noticed a choroidal lesion which he suspected to be a reaction to
      the laser treatment and referred the patient to our hospital where a diagnosis of
      a mushroom-shaped choroidal melanoma with serous retinal detachment was made.
      These cases show that preoperative evaluation of the posterior segment prior to
      cataract surgery or other therapeutic interventions is essential in order to
      identify any pathology. In case of a dense cataract, additional imaging such as
      ultrasound sonography is recommended in order to exclude intraocular lesions and
      to visualize the optic disc in suspected glaucoma.

PMID- 22610450
TI  - Pigment epithelium-derived factor is related to macular microcirculation in
      patients with macular edema and branch retinal vein occlusion.
AB  - To investigate the correlation between the perifoveal capillary blood flow
      velocity (BFV) and the vitreous level of pigment epithelium-derived factor (PEDF)
      in patients with branch retinal vein occlusion (BRVO) and macular edema. In a
      retrospective interventional study of patients with BRVO and macular edema,
      undiluted vitreous specimens were obtained from 12 eyes of 12 patients. The level
      of PEDF was then measured in vitreous samples by an enzyme-linked immunosorbent
      assay. Before vitreous fluid sampling, perifoveal capillary BFV was measured by
      fluorescein angiography with a scanning laser ophthalmoscope and the tracing
      method. Subsequently, the relationship between perifoveal capillary BFV and the
      vitreous level of PEDF was investigated. There was a significant positive
      correlation between BFV and the vitreous level of PEDF in the 12 patients (rho =
      0.75, p = 0.013). The vitreous level of PEDF may influence macular
      microcirculation in patients with BRVO and macular edema.

PMID- 22610451
TI  - Late-onset capsular block syndrome.
AB  - We describe two patients with late-onset capsular block syndrome who presented 6
      years and 4 years, respectively, after cataract surgery and were successfully
      treated with Nd:YAG capsulotomy.

PMID- 22610453
TI  - Presence versus absence of hydrogen bond donor Tyr-39 influences interactions of
      cationic trypsin and mesotrypsin with protein protease inhibitors.
AB  - Mesotrypsin displays unusual resistance to inhibition by polypeptide trypsin
      inhibitors and cleaves some such inhibitors as substrates, despite a high degree
      of conservation with other mammalian trypsins. Substitution of Arg for the
      generally conserved Gly-193 has been implicated as a critical determinant of the
      unusual behavior of mesotrypsin toward protein protease inhibitors. Another
      relatively conserved residue near the trypsin active site, Tyr-39, is substituted
      by Ser-39 in mesotrypsin. Tyr-39, but not Ser-39, forms a hydrogen bond with the
      main chain amide nitrogen of the P(4) ' residue of a bound protease inhibitor. To
      investigate the role of the Tyr-39 H-bond in trypsin-inhibitor interactions, we
      reciprocally mutated position 39 in mesotrypsin and human cationic trypsin to Tyr
      39 and Ser-39, respectively. We assessed inhibition constants and cleavage rates
      of canonical protease inhibitors bovine pancreatic trypsin inhibitor (BPTI) and
      the amyloid precursor protein Kunitz protease inhibitor domain by mesotrypsin and
      cationic trypsin variants, finding that the presence of Ser-39 relative to Tyr-39
      results in a 4- to 13-fold poorer binding affinity and a 2- to 18-fold increase
      in cleavage rate. We also report the crystal structure of the mesotrypsin
      S39Y*BPTI complex, in which we observe an H-bond between Tyr-39 OH and BPTI Ile
      19 N. Our results indicate that the presence of Ser-39 in mesotrypsin, and
      corresponding absence of a single H-bond to the inhibitor backbone, makes a small
      but significant functional contribution to the resistance of mesotrypsin to
      inhibition and the ability of mesotrypsin to proteolyze inhibitors.

PMID- 22610452
TI  - Inhaled hypertonic saline in infants and children younger than 6 years with
      cystic fibrosis: the ISIS randomized controlled trial.
AB  - CONTEXT: Inhaled hypertonic saline is recommended as therapy for patients 6 years
      or older with cystic fibrosis (CF), but its efficacy has never been evaluated in
      patients younger than 6 years with CF. OBJECTIVE: To determine if hypertonic
      saline reduces the rate of protocol-defined pulmonary exacerbations in patients
      younger than 6 years with CF. DESIGN, SETTING, AND PARTICIPANTS: The Infant Study
      of Inhaled Saline in Cystic Fibrosis (ISIS), a multicenter, randomized, double
      blind, placebo-controlled trial conducted from April 2009 to October 2011 at 30
      CF care centers in the United States and Canada. Participants were aged 4 to 60
      months and had an established diagnosis of CF. A total of 344 patients were
      assessed for eligibility; 321 participants were randomized; 29 (9%) withdrew
      prematurely. INTERVENTION: The active treatment group (n = 158) received 7%
      hypertonic saline and the control group (n = 163) received 0.9% isotonic saline,
      nebulized twice daily for 48 weeks. Both groups received albuterol or
      levalbuterol prior to each study drug dose. MAIN OUTCOME MEASURES: Rate during
      the 48-week treatment period of protocol-defined pulmonary exacerbations treated
      with oral, inhaled, or intravenous antibiotics. RESULTS: The mean pulmonary
      exacerbation rate (events per person-year) was 2.3 (95% CI, 2.0-2.5) in the
      active treatment group and 2.3 (95% CI, 2.1-2.6) in the control group; the
      adjusted rate ratio was 0.98 (95% CI, 0.84-1.15). Among participants with
      pulmonary exacerbations, the mean number of total antibiotic treatment days for a
      pulmonary exacerbation was 60 (95% CI, 49-70) in the active treatment group and
      52 (95% CI, 43-61) in the control group. There was no significant difference in
      secondary end points including height, weight, respiratory rate, oxygen
      saturation, cough, or respiratory symptom scores. Infant pulmonary function
      testing performed as an exploratory outcome in a subgroup (n = 73, with
      acceptable measurements at 2 visits in 45 participants) did not demonstrate
      significant differences between groups except for the mean change in forced
      expiratory volume in 0.5 seconds, which was 38 mL (95% CI, 1-76) greater in the
      active treatment group. Adherence determined by returned study drug ampoules was
      at least 75% in each group. Adverse event profiles were also similar, with the
      most common adverse event of moderate or severe severity in each group being
      cough (39% of active treatment group, 38% of control group). CONCLUSION: Among
      infants and children younger than 6 years with cystic fibrosis, the use of
      inhaled hypertonic saline compared with isotonic saline did not reduce the rate
      of pulmonary exacerbations over the course of 48 weeks of treatment. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00709280.

PMID- 22610454
TI  - Autochthonous and migratory birds as a dispersion source for Ixodes ricinus in
      southern Italy.
AB  - The present study was carried out in a protected wooded area, which is part of
      the Parco Regionale Gallipoli Cognato Piccole Dolomiti Lucane, one of the most
      important ecological reserves in southern Italy. From April 2010 to April 2011,
      212 birds, comprising 22 species from 12 families, were captured and examined for
      ticks. A total of 75 (35.4 %) birds were found infested by ticks, with 451 ticks
      being collected. All ticks were identified as Ixodes ricinus, of which 241 (53.4
      %) were larvae and 210 nymphs (46.6 %). The highest intensity of infestation was
      found in April 2010, when 117 ticks were retrieved on 25 birds. No ticks were
      found on birds (n = 5) netted in December 2010. High infestation rates were
      recorded on blackbirds (Turdus merula) (90 %; 29 birds examined) and on mistle
      thrushes (Turdus viscivorus) (100 %; 2 birds examined). The highest intensity of
      infestation by larvae was found on wrens (5.6 larvae/bird) and by nymphs on
      mistle thrushes (11.5 nymphs/bird). Temperature and number of hours of light
      showed to influence the activity of larvae and nymphs. These data support the
      notion that birds may be responsible for the heterogeneous distribution of I.
      ricinus in Europe, thus playing a role in the epidemiology of certain tick-borne
      pathogens.

PMID- 22610455
TI  - Rare late mesh complications following inguinal prolene hernia system
      hernioplasty: report of three cases.
AB  - We have treated three patients who developed late mesh infections 7 years after
      inguinal hernioplasty caused by contact of an underlay prolene hernia system
      (PHS) patch with the intestines. In two patients, the cause was the development
      of a fistula between the underlay patch preperitoneally positioned in Bogros
      space and the appendix, and in one, a sigmoid colon fistula that developed as a
      consequence of penetration of the underlay PHS patch into the sigmoid colon. In
      the patients with contact of an underlay PHS patch with the appendix, total PHS
      excision, appendectomy, McVay herniorrhaphy and drainage through a direct
      inguinal approach were applied. In the patient with a sigmoid colon lesion, total
      PHS excision, left hemicastration, suturing of the sigmoid colon fistula, and a
      McVay herniorrhaphy with drainage were performed through a direct inguinal
      approach, followed by midline laparotomy and protective bipolar ileostomy. Late
      mesh infection developing several years after PHS inguinal hernioplasty is
      usually the consequence of intestinal erosions and fistulas due to contact
      between the underlay PHS patch and the intestines.

PMID- 22610456
TI  - Young-onset peri-anorectal leiomyomatosis: report of a case.
AB  - A 23-year-old female was referred with constipation that lasted for 2 years.
      Preoperative examinations revealed multiple submucosal tumors beside the
      anorectum, along with subcutaneous tumors in the left buttock. The pathological
      diagnosis was leiomyoma. Low anterior resection of the rectum with regional lymph
      node dissection, along with the resection of the subcutaneous tumors in the left
      buttock through the transdermal approach, was performed, since multiple tumor
      formation indicated a high malignant potential. The tumors were diagnosed as
      multiple leiomyomas with no malignancy. Disease categories such as intravenous
      leiomyomatosis, leiomyomatosis peritonealis disseminata, Alport syndrome, and
      Currarino syndrome have been reported to be associated with leiomyomatosis;
      however, the current case of "peri-anorectal leiomyomatosis" was not classified
      into any of these. The patient was monitored with careful checkups, and the
      postoperative course was satisfactory for over 5 years without any sign of
      recurrence or metastasis. Although the clinicopathological features of this case
      are quite rare and no therapeutic guidelines for such a disease have yet been
      established, radical resection should be considered, and the elucidation of the
      histogenesis of this disease will help establish future therapeutic guidelines.

PMID- 22610457
TI  - E. coli O157:H7 and other toxigenic strains: the curse of global food
      distribution.
AB  - It is estimated that there are approximately 76 million illnesses, 325,000
      hospitalizations, and 5,200 deaths in the US each year attributed to foodborne
      outbreaks with a total cost of 10-83 billion US dollars a year. While the rates
      of foodborne disease have remained relatively constant over the last few years,
      there have been large outbreaks associated with either a component of
      commercially prepared food or outbreaks that span between states or even
      countries. With the world population expecting fresh produce year round, organic
      produce, and exotic foods, these global outbreaks have the potential to increase
      in number and severity. There needs to be a means to both rapidly identify these
      outbreaks, screen our food supply, as well as prevent these outbreaks. This
      article will discuss the global nature of this problem associated with our food
      and water supply as well as explain potential ways to solve this international
      problem.

PMID- 22610459
TI  - Update on dystonia.
AB  - PURPOSE OF REVIEW: This review considers the recent literature pertaining to the
      clinical features, genetics, neuropathology and treatment of dystonia syndromes.
      RECENT FINDINGS: The term dystonia indicates at the same time a clinical
      phenotype and a collection of neurological syndromes mainly of genetic origin.
      The physical signs contributing to the phenomenology of dystonia have been
      recently assembled into a coherent set. The molecular genetics of primary
      dystonia syndromes (DYT1 and DYT6) have been the object of extensive analysis,
      providing converging views on their causative mechanisms. The relationship
      between genotype, phenotype, and endophenotypes has been explored for hereditary
      and sporadic dystonia syndromes. Neurophysiological studies on DYT1 and DYT6
      patients, as well as on nonmanifesting carriers, have demonstrated the presence
      of altered synaptic plasticity. Several recent data indicate a role of dopamine
      and acetylcholine (ACh) transmission in the pathophysiology of primary dystonia.
      SUMMARY: Recent findings have led to novel, testable hypotheses on cellular
      mechanisms and physiopathological abnormalities underlying dystonia.
      Neurophysiological studies, imaging data and animal models support the view that
      corticostriatal, cerebellar, and dopaminergic dysfunctions converge to produce
      the pathophysiological abnormalities of dystonia.

PMID- 22610458
TI  - Arterial spin labeling MRI:  an emerging biomarker for Alzheimer's disease and
      other neurodegenerative conditions.
AB  - PURPOSE OF REVIEW: The search for biomarkers that detect and track disease
      progression in early Alzheimer's disease has been a major pursuit for two
      decades. Functional measures reflecting alterations of synaptic activity
      associated with neuronal dysfunction have displayed promise for following disease
      course in early stages. Although fluorodeoxyglucose positron emission tomography
      (FDG PET) and blood oxygen level-dependent functional MRI (BOLD fMRI) have been
      studied extensively for this purpose, this review will discuss the emergence and
      potential role of arterial spin labeling (ASL) MRI, which measures cerebral blood
      flow (CBF), in neurodegeneration. RECENT FINDINGS: Several recent studies have
      explored ASL MRI in early and prodromal Alzheimer's disease and have reported
      areas of hypoperfusion that overlap considerably with hypometabolism frequently
      reported with FDG PET. However, some studies have also noted increased regional
      CBF of patients with prodromal and early stage clinical Alzheimer's disease,
      which may have implications for pathophysiology and the role of compensatory
      responses to neurodegeneration. Additionally, a few recent studies have begun to
      use this modality to explore the role of cerebrovascular factors in cognitive
      decline and the relationship to Alzheimer's disease. SUMMARY: ASL MRI is just
      beginning to be applied more widely to various neurodegenerative conditions.
      Initial data suggest that this methodology may provide similar information to FDG
      PET, but with several advantages in the ease of acquisition and expense.
      Additional applications of this modality, including task-related studies and
      testing of pharmacological effects, are underexplored, but are potentially of
      significant value in understanding disease-related functional changes and
      treatment effects.

PMID- 22610460
TI  - Functional (psychogenic) movement disorders.
AB  - PURPOSE OF REVIEW: This review provides an overview of recent developments in
      diagnosis, pathophysiology, neuroimaging and management of functional
      (psychogenic) movement disorders (FMD). RECENT FINDINGS: There has been
      increasing interest to study the underlying pathophysiology of FMD, which has
      resulted in a broadened disease model, taking neurobiologic and psychosocial
      factors equally into account. In this context, the term 'psychogenic' has been
      replaced by 'functional' movement disorders by many authors in the field to
      express the changing focus toward a multifactorial disease model. The need for
      establishing a positive diagnosis of FMD as opposed to providing a diagnosis of
      exclusion is increasingly recognized and reflected by the introduction of
      'laboratory-supported' diagnostic criteria of FMD. Important advances have been
      made through behavioral, electrophysiological and neuroimaging studies, although
      the fundamental cause of FMD remains poorly understood. Of particular interest
      have been several reports on abnormal sensorimotor features and cortical
      inhibition in both organic and functional dystonia, highlighting possible shared
      traits of both conditions. In terms of treatment, recent studies have reported
      benefit from both psychiatric and physical therapy-based interventions. SUMMARY:
      Increasing efforts have been made toward better understanding of FMD, and the
      disease model has been broadened to include neurobiologic and psychosocial
      factors. Laboratory-based diagnostic criteria have been established for many FMD
      to support the clinical diagnosis. To determine the most effective management
      strategies for FMD, a closer collaboration between neurologists and psychiatrists
      and intensified research efforts with prospective treatment trials are needed.

PMID- 22610461
TI  - Independent effects of geometry and landmark in a spontaneous reorientation task:
      a study of two species of fish.
AB  - While disoriented humans and animals use both landmarks and environmental
      geometry to guide their navigation, it is not clear what kinds of cognitive
      mechanisms underlie these behaviors. Because traditional tests of trained
      navigation behavior in environments containing both landmarks and geometric
      information may cloud our insight into the nature of these processes, the present
      study tested the spontaneous use of landmarks and environmental shape by two
      species of fish-Redtail Splitfins (Xenotoca eiseni) and Zebrafish (Danio rerio).
      The results suggest that while geometry is spontaneously used by both species and
      both sexes to compute relative position or direction, the spontaneous use of
      landmarks is limited to direct beaconing and complicated by attraction to
      features and variability across species and sex. These findings support the view
      that while multiple cues may ultimately guide behavior, the computation of
      orientation and relative positions is specified by geometric input and is
      independent from other navigation processes such as beaconing.

PMID- 22610462
TI  - Chromogen-based immunohistochemical method for elucidation of the coexpression of
      two antigens using antibodies from the same species.
AB  - The authors established a chromogen-based, double immunolabeling method using
      antibodies from the same species without any unwanted cross-reactivity. In
      addition, time-consuming staining steps were shortened by using polymer-based
      secondary antibodies. Taking advantage of the nature of the chromogen 3-amino-9
      ethylcarbazole (AEC), which is used as a horseradish peroxidase substrate for
      antibody detection, the AEC-derived signals in the first color development were
      easily eliminated by alcohol treatment. Therefore, the signals from the first
      staining did not interfere with those from the subsequent second staining, which
      used the chromogen 3,3'-diaminobenzidine. The co-localization of antigens within
      the same cell could be confirmed using this method, because cell images of the
      individual dye staining steps could be obtained and developed. The images from
      each step could be expressed in pseudo-colors in a dark field by using a
      computer. As a result, merged images could be constructed that resembled the
      images acquired by the fluorescent immunolabeling technique. The resolution of
      this method enabled analysis of the coexpression of two antigens in the same cell
      in the same section. The authors have named this staining technique the
      elucidation of the coexpression of two antigens in a cell using antibodies from
      the same species (ECSS).

PMID- 22610464
TI  - Comparison of the quick mild cognitive impairment (Qmci) screen and the SMMSE in
      screening for mild cognitive impairment.
AB  - INTRODUCTION: differentiating mild cognitive impairment (MCI) from normal
      cognition (NC) is difficult. The AB Cognitive Screen (ABCS) 135, sensitive in
      differentiating MCI from dementia, was modified to improve sensitivity and
      specificity, producing the quick mild cognitive impairment (Qmci) screen.
      OBJECTIVE: this study compared the sensitivity and specificity of the Qmci with
      the Standardised MMSE and ABCS 135, to differentiate NC, MCI and dementia.
      METHODS: weightings and subtests of the ABCS 135 were changed and a new section
      'logical memory' added, creating the Qmci. From four memory clinics in Ontario,
      Canada, 335 subjects (154 with MCI, 181 with dementia) were recruited and
      underwent comprehensive assessment. Caregivers, attending with the subjects,
      without cognitive symptoms, were recruited as controls (n = 630). RESULTS: the
      Qmci was more sensitive than the SMMSE and ABCS 135, in differentiating MCI from
      NC, with an area under the curve (AUC) of 0.86 compared with 0.67 and 0.83,
      respectively, and in differentiating MCI from mild dementia, AUC of 0.92 versus
      0.91 and 0.91. The ability of the Qmci to identify MCI was better for those over
      75 years. CONCLUSION: the Qmci is more sensitive than the SMMSE in
      differentiating MCI and NC, making it a useful test, for MCI in clinical
      practice, especially for older adults.

PMID- 22610463
TI  - Hyaline cartilage tissue is formed through the co-culture of passaged human
      chondrocytes and primary bovine chondrocytes.
AB  - To circumvent the problem of a sufficient number of cells for cartilage
      engineering, the authors previously developed a two-stage culture system to
      redifferentiate monolayer culture-expanded dedifferentiated human articular
      chondrocytes by co-culture with primary bovine chondrocytes (bP0). The aim of
      this study was to analyze the composition of the cartilage tissue formed in stage
      1 and compare it with bP0 grown alone to determine the optimal length of the co
      culture stage of the system. Biochemical data show that extracellular matrix
      accumulation was evident after 2 weeks of co-culture, which was 1 week behind the
      bP0 control culture. By 3 to 4 weeks, the amounts of accumulated proteoglycans
      and collagens were comparable. Expression of chondrogenic genes, Sox 9, aggrecan,
      and collagen type II, was also at similar levels by week 3 of culture.
      Immunohistochemical staining of both co-culture and control tissues showed
      accumulation of type II collagen, aggrecan, biglycan, decorin, and chondroitin
      sulfate in appropriate zonal distributions. These data indicate that co-cultured
      cells form cartilaginous tissue that starts to resemble that formed by bP0 after
      3 weeks, suggesting that the optimal time to terminate the co-culture stage,
      isolate the now redifferentiated cells, and start stage 2 is just after 3 weeks.

PMID- 22610465
TI  - Multi-spectroscopic methods combined with molecular modeling dissect the
      interaction mechanisms of ractopamine and calf thymus DNA.
AB  - The toxic interaction of ractopamine (RAC) with calf thymus DNA (ct DNA) was
      studied in vitro using multi-spectroscopic methods and molecular modeling
      methods. The hypochromic effect without a noticeable shift in UV-vis absorption
      indicated that the minor groove binding mode existed in the interaction between
      RAC and DNA. The fluorescence quenching of RAC was observed with the increasing
      addition of DNA and was proved to be the static quenching. The binding constant
      and the binding site sizes were 4.13 * 10(3) and 0.97, respectively. The
      thermodynamic calculation demonstrated that the hydrogen bond and van der Waals
      were main acting forces. This result further confirmed the existence of groove
      binding mode. Afterwards, we found another interaction mode, electrostatic
      binding mode through the fluorescence polarization, ionic effects and denatured
      DNA experiments. Circular dichroism spectroscopy (CD) was then employed to
      monitor the conformation changes of DNA. Molecular modeling studies illustrated
      the visual display of the binding mode and the detailed information of the H
      bond.

PMID- 22610466
TI  - The Hunter syndrome-functional outcomes for clinical understanding scale (HS
      FOCUS) questionnaire: evaluation of measurement properties.
AB  - PURPOSE: This study was to conduct the psychometric validation of the patient and
      parent versions of the Hunter syndrome-functional outcomes for clinical
      understanding scale (HS-FOCUS). METHODS: Data collected in a 53-week placebo
      controlled multinational trial were used to evaluate item performance and
      reliability, validity, and ability to detect change of the six HS-FOCUS function
      domains. RESULTS: HS-FOCUS was completed by 49 patients above 12 years old and 84
      parents. Floor effects and high average inter-item correlations suggested that
      some items were less informative or redundant. For both patients and parents, the
      internal consistency and test-retest reliability met the >0.70 criteria for all
      domains except for the breathing, sleeping, and schooling/work in patients.
      Construct validity showed moderate to high correlations with CHAQ, CHQ, and HUI3
      in activity-related concepts. Significant differences in domain scores were found
      in most domains among severity in disability measured by CHAQ DIS. Significant
      differences in HS-FOCUS change scores were found in patients whose CHAQ DIS score
      also changed. CONCLUSIONS: Psychometric validation of the HS-FOCUS demonstrates
      it is a reliable, valid, and responsive instrument that can be applied in
      clinical trials or disease registries. Findings on the individual item
      performance suggest some items could be removed without compromising its
      validity.

PMID- 22610467
TI  - Release behavior of tanshinone IIA sustained-release pellets based on crack
      formation theory.
AB  - The objective of this study was to investigate the drug release mechanism and in
      vivo performance of Tanshinone IIA sustained-release pellets, coated with blends
      of polyvinyl acetate (PVAc) and poly(vinyl alcohol)-poly(ethylene glycol) (PVA
      PEG) graft copolymer. A formulation screening study showed that pellets coated
      with PVAc-PVA-PEG at a ratio of 70:30 (w/w) succeeded in achieving a 24 h
      sustained release, irrespective of the coating weight (from 2% to 10%). Both the
      microscopic observation and mathematical model gave further insight into the
      underlying release mechanism, indicating that diffusion through water-filled
      cracks was dominant for the control of drug release. In vivo test showed that the
      maximum plasma concentration of sustained-release pellets was decreased from
      82.13 +/- 17.05 to 40.50 +/- 11.72 ng mL as that of quick-release pellets. The
      time of maximum concentration, half time, and mean residence time were all
      prolonged from 3.80 +/- 0.40 to 8.02 +/- 0.81 h, 4.28 +/- 1.21 to 8.18 +/- 2.06
      h, and 8.60 +/- 1.59 to 17.50 +/- 2.78 h, compared with uncoated preparations. A
      good in vitro-in vivo correlation was characterized by a high coefficient of
      determination (r = 0.9772). In conclusion, pellets coated with PVAc-PVA-PEG could
      achieve a satisfactory sustained-release behavior based on crack formation
      theory.

PMID- 22610469
TI  - Superior mesenteric artery syndrome in a patient with autism spectrum disorder:
      case report and review of the literature.

PMID- 22610468
TI  - New Drosophila P-like elements and reclassification of Drosophila P-elements
      subfamilies.
AB  - Genomic searches for P-like transposable elements were performed (1) in silico in
      the 12 available Drosophila genomes and (2) by PCR using degenerate primers in 21
      Neotropical Drosophila species. In silico searches revealed P-like sequences only
      in Drosophila persimilis and Drosophila willistoni. Sixteen new P-like elements
      were obtained by PCR. These sequences were added to sequences of previously
      described P-like elements, and a phylogenetic analysis was performed. The
      subfamilies of P-elements described in the literature (Canonical, M, O, T, and K)
      were included in the reconstructed tree, and all were monophyletic. However, we
      suggest that some subfamilies can be enlarged, other subdivided, and some new
      subfamilies may be proposed, totalizing eleven subfamilies, most of which contain
      new P-like sequences. Our analyses support the monophyly of P-like elements in
      Drosophilidae. We suggest that, once these elements need host-specific factors to
      be mobilizable, the horizontal transfer (HT) of P-like elements may be inhibited
      among more distant taxa. Nevertheless, HT among Drosophilidae species appears to
      be a common phenomenon.

PMID- 22610470
TI  - Twin studies in autism: what might they say about genetic and environmental
      influences.
AB  - Genetic and epigenetic differences exist within monozygote twin-pairs and might
      be especially important in the expression of autism. Assuming phenotypic
      differences between monozygotic twins are due to environmental influences may
      lead to mistaken conclusions regarding the relative genetic and environmental
      contribution to autism risk.

PMID- 22610471
TI  - Predictors of leisure time physical activity among people with spinal cord
      injury.
AB  - BACKGROUND: Most studies of physical activity predictors in people with
      disability have lacked a guiding theoretical framework. Identifying theory-based
      predictors is important for developing activity-enhancing strategies. PURPOSE: To
      use the World Health Organization's International Classification of Functioning,
      Disability and Health (ICF) framework to identify predictors of leisure time
      physical activity among people with spinal cord injury (SCI). METHODS: Six
      hundred ninety-five persons with SCI (M age=47; 76% male) completed measures of
      Body Functions and Structures, Activities and Participation, Personal Factors,
      and Environmental Factors at baseline and 6-months. Activity was measured at 6
      and 18 months. Logistic and linear regression models were computed to
      prospectively examine predictors of activity status and activity minutes per day.
      RESULTS: Models explained 19%-25% of variance in leisure time physical activity.
      Activities and Participation and Personal Factors were the strongest, most
      consistent predictors. CONCLUSIONS: The ICF framework shows promise for
      identifying and conceptualizing predictors of leisure time physical activity in
      persons with disability.

PMID- 22610472
TI  - Type D personality and cardiovascular outcomes.

PMID- 22610473
TI  - Doing what feels good (and avoiding what feels bad)--a growing recognition of the
      influence of affect on exercise behavior: a comment on Williams et al.

PMID- 22610474
TI  - Estimating smoking-attributable mortality in the United States.
AB  - Tobacco use is the largest single cause of premature death in the developed
      world. Two methods of estimating the number of deaths attributable to smoking use
      mortality from lung cancer as an indicator of the damage from smoking. We re
      estimate the coefficients of one of these, the Preston/Glei/Wilmoth model, using
      recent data from U.S. states. We calculate smoking-attributable fractions for the
      50 states and the United States as a whole in 2004, and estimate the contribution
      of smoking to the high adult mortality of the southern states. We estimate that
      21% of deaths among men and 17% among women were attributable to smoking in 2004.
      Across states, attributable fractions range from 11% to 30% among men and from 7%
      to 23% among women. Smoking-related mortality also explains as much as 60% of the
      mortality disadvantage of southern states compared with other regions. At the
      national level, our estimates are in close agreement with those of the Centers
      for Disease Control and Prevention and Preston/Glei/Wilmoth, particularly for
      men, although we find greater variability by state than does CDC. We suggest that
      our coefficients are suitable for calculating smoking-attributable mortality in
      contexts with relatively mature epidemics of cigarette smoking.

PMID- 22610475
TI  - Pleiotropic effects of calcium channel blockers.
AB  - Clinical trials have reported reduced cardiovascular events with certain
      antihypertensive agents at a rate that could not be predicted by changes in
      brachial arterial pressure alone. These findings may be explained, in part, by
      pleiotropic effects of these agents and modulation of central blood pressures.
      This review focuses on the mechanisms by which calcium channel blockers exert
      pleiotropic effects, both alone and in combination with statins and inhibitors of
      the renin-angiotensin system. The essential role of nitric oxide (NO) in
      maintaining endothelial function and the relationship between NO and reactive
      oxygen species are discussed in the context of the etiology of hypertension. The
      importance of managing global cardiovascular risk is emphasized, as hypertension
      commonly clusters with dyslipidemia and loss of glucose control. From a
      mechanistic viewpoint, these risk factors contribute to endothelial dysfunction,
      oxidative stress, and inflammation in a synergistic fashion. A greater
      understanding of the mechanisms of actions of these cardiovascular agents may
      lead to more effective drug combinations, to the benefit of individual patients.
      Furthermore, by elucidating the biological mechanisms by which cardiovascular
      risk factors lead to vascular injury, we may highlight common pathways and
      identify novel therapeutic targets.

PMID- 22610476
TI  - Nonsteroidal antiinflammatory drugs, acetaminophen, and hypertension.
AB  - Selective and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) as
      well as acetaminophen belong to the most widely prescribed therapeutic agents
      worldwide. Their efficacy in pain relief notwithstanding, the use of NSAIDs is
      associated with an increased cardiovascular risk, which can be partly attributed
      to their blood pressure raising potential. Adequately powered placebo-controlled
      trials specifically evaluating the cardiovascular safety of NSAIDs vs. selective
      COX inhibitors are currently underway. This review summarizes the current
      knowledge on the cardiovascular effects of NSAIDs and acetaminophen, and their
      potential clinical consequences.

PMID- 22610477
TI  - Inhaled hypertonic saline in infants and young children with cystic fibrosis.

PMID- 22610478
TI  - Effect of prolonged storage of seminal plasma on levels of calcium and magnesium.
AB  - BACKGROUND: In laboratories, the semen or seminal plasma samples are stored
      before estimation of different elements without knowing the adverse effect of
      storing. The present study shows the levels of Ca++ and Mg++ in the seminal
      plasma before and after the storage. METHODS: Atomic absorption spectrophotometry
      (AAS) was used for estimating calcium and magnesium levels in the seminal plasma.
      Samples were stored for one year in different containers such as polyethylene,
      plastic, ordinary glass, and borosil glass. Calcium and magnesium levels were
      estimated after this period by AAS. The total area in contact with containers was
      considered in the final calculation. RESULTS: After 1-year storage, the levels of
      calcium and magnesium had changed. The most suitable container for storage of
      calcium was ordinary glass (P > 0.05) whereas ordinary glass (P > 0.05),
      polyethylene (P > 0.05), and borosil glass (P > 0.05) are the most suitable for
      magnesium. CONCLUSION: In any elemental study, the most suitable containers are
      recommended for storage of the semen/seminal plasma samples.

PMID- 22610479
TI  - Learning-dependent plasticity in human auditory cortex during appetitive operant
      conditioning.
AB  - Animal experiments provide evidence that learning to associate an auditory
      stimulus with a reward causes representational changes in auditory cortex.
      However, most studies did not investigate the temporal formation of learning
      dependent plasticity during the task but rather compared auditory cortex
      receptive fields before and after conditioning. We here present a functional
      magnetic resonance imaging study on learning-related plasticity in the human
      auditory cortex during operant appetitive conditioning. Participants had to learn
      to associate a specific category of frequency-modulated tones with a reward. Only
      participants who learned this association developed learning-dependent plasticity
      in left auditory cortex over the course of the experiment. No differential
      responses to reward predicting and nonreward predicting tones were found in
      auditory cortex in nonlearners. In addition, learners showed similar learning
      induced differential responses to reward-predicting and nonreward-predicting
      tones in the ventral tegmental area and the nucleus accumbens, two core regions
      of the dopaminergic neurotransmitter system. This may indicate a dopaminergic
      influence on the formation of learning-dependent plasticity in auditory cortex,
      as it has been suggested by previous animal studies.

PMID- 22610480
TI  - Apoptosis induced by 1,3,6,7-tetrahydroxyxanthone in Hepatocellular carcinoma and
      proteomic analysis.
AB  - Gamboge is a traditional Chinese medicine and our previous study showed that
      gambogic acid and gambogenic acid suppress the proliferation of HCC cells. In the
      present study, another active component, 1,3,6,7-tetrahydroxyxanthone (TTA), was
      identified to effectively suppress HCC cell growth. In addition, our Hoechst-PI
      staining and flow cytometry analyses indicated that TTA induced apoptosis in HCC
      cells. In order to identify the targets of TTA in HCC cells, a two-dimensional
      gel electrophoresis was performed, and proteins in different expressions were
      identified by MALDA-TOF MS and MS/MS analyses. In summary, eighteen proteins with
      different expressions were identified in which twelve were up-regulated and six
      were down-regulated. Among them, the four most distinctively expressed proteins
      were further studied and validated by western blotting. The beta-tubulin and
      translationally controlled tumor protein were decreased while the 14-3-3sigma and
      P16 protein expressions were up-regulated. In addition, TTA suppressed
      tumorigenesis partially through P16-pRb signaling. 14-3-3sigma silence reversed
      the suppressive effect of cell growth and apoptosis induced by introducing TTA.
      In conclusion, TTA effectively suppressed cell growth through, at least
      partially, up-regulation of P16 and 14-3-3sigma.

PMID- 22610482
TI  - Current world literature.

PMID- 22610481
TI  - TSSC3 overexpression reduces stemness and induces apoptosis of osteosarcoma tumor
      initiating cells.
AB  - Osteosarcoma (OS) is the most common primary bone tumor in children and
      adolescents, typically presenting with poor prognosis. Recent studies suggested
      that tumor initiating cells (T-ICs) drive tumor formation and relapse or
      metastasis and are relatively resistant to cell death induced by conventional
      chemo- and radiotherapies. Therefore, the poor prognosis of OS appears to be
      associated with T-ICs. Here, we enriched T-ICs in OS cell lines and evaluated
      whether the imprinted gene TSSC3 (tumor-suppressing STF cDNA 3) associated with
      apoptosis could affect T-ICs in OS. Sarcosphere selection and serial clone
      forming unit assays were successfully used to enrich T-ICs from OS cell lines.
      Enrichment of T-ICs from a malignantly transformed hFOB1.19 osteoblast cell line
      (MThFOB1.19) indicated that OS T-ICs could originate from differentiated cells,
      and most of these MThFOB1.19 cells showed stem-like features. TSSC3 was expressed
      at a low level in T-ICs, while overexpression of TSSC3 could efficiently
      downregulate the expression of stem cell markers Nanog, Oct4 and Sox2 in T-ICs
      and decrease the clone formation rate, as well as downregulate tumorigenesis in
      MThFOB1.19 cells, supporting a suppressive role for TSSC3 in OS T-ICs.
      Furthermore, overexpression of TSSC3 was found to induce apoptosis of OS T-ICs
      through increasing cleaved caspase-3 (active form), increasing the release of Cyt
      c and decreasing pro-caspase-9 (pro-enzyme form), as well as disruption of the
      mitochondrial membrane potential (DeltaPsi). Taken together, our findings provide
      preliminary evidence that TSSC3 inhibits OS tumorigenicity through reducing
      stemness and promoting apoptosis of T-ICs. Thus, targeting TSSC3 may be a
      promising approach to suppressing tumorigenicity in OS.

PMID- 22610484
TI  - Isolated central nervous system relapses in primary mediastinal large B-cell
      lymphoma after CHOP-like chemotherapy with or without Rituximab.
AB  - Central nervous system (CNS) involvement in patients with primary mediastinal
      large B-cell (PMLBCL) lymphoma is a rare event, occurring in approximately 6% of
      patients, on the basis of the review of the literature prior to induction of
      Rituximab. The aim of this retrospective study was to describe the incidence of
      CNS relapse among 100 consecutive patients with PMLBCL who were treated with R
      CHOP +/- RT in comparison to patients treated with CHOP +/- RT (n = 45) in 11
      hospitals in Greece. Two patients experienced a CNS relapse, representing an
      overall frequency of 2.0% in R-CHOP treated patients and a 2-year actuarial
      incidence of 2.3%. Both patients had isolated CNS relapses. The incidence of CNS
      relapse after CHOP without Rituximab was 2/45 (4.4%) for a 2-year actuarial
      incidence of 7.5% (p = 0.29). Again, both patients had isolated CNS relapses.
      Parenchymal-only localizations accounted for 3/4 cases. Risk factors for CNS
      involvement could include leukocytosis, poor performance status and higher age
      adjusted International Prognostic Index, although their impact was weakened by
      competing risk survival analysis. Both patients relapsing after R-CHOP required
      CNS radiotherapy to achieve a complete remission and be forwarded to high-dose
      therapy and autologous stem cell transplantation: They are both alive and disease
      free 18 and 23 months after CNS relapse. Both cases relapsing after CHOP without
      Rituximab were salvaged by CNS radiotherapy (one also received intrathecal
      chemotherapy) entering long-term remissions. In conclusion, CNS relapses are rare
      in PMLBCL tending to be isolated in the CNS, probably reflecting the persistence
      of latent CNS disease than dissemination of resistant disease. The impact of
      Rituximab in reducing CNS relapses remains unknown. Established risk factors for
      CNS involvement in aggressive lymphomas may not be helpful in assessing the risk
      of CNS recurrence in this disease. Routine CNS prophylaxis is not probably
      required in PMLBCL.

PMID- 22610485
TI  - Functional significance of four successive glycine residues in the pyrophosphate
      binding loop of fungal 6-oxopurine phosphoribosyltransferases.
AB  - Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is a key enzyme of the
      purine recycling pathway that catalyzes the conversion of 5-phospho-ribosyl-alpha
      1-pyrophosphate and guanine or hypoxanthine to guanosine monophosphate (GMP) or
      inosine monophosphate (IMP), respectively, and pyrophosphate (PPi). We report the
      first crystal structure of a fungal 6-oxopurine phosphoribosyltransferase, the
      Saccharomyces cerevisiae HGPRT (Sc-HGPRT) in complex with GMP. The crystal
      structures of full length protein with (WT1) or without (WT2) sulfate that mimics
      the phosphate group in the PPi binding site were solved by molecular replacement
      using the structure of a truncated version (Delta7) solved beforehand by
      multiwavelength anomalous diffusion. Sc-HGPRT is a dimer and adopts the overall
      structure of class I phosphoribosyltransferases (PRTs) with a smaller hood domain
      and a short two-stranded parallel beta-sheet linking the N- to the C-terminal
      end. The catalytic loops in WT1 and WT2 are in an open form while in Delta7, due
      to an inter-subunit disulfide bridge, the catalytic loop is in either an open or
      closed form. The closure is concomitant with a peptide plane flipping in the PPi
      binding loop. Moreover, owing the flexibility of a GGGG motif conserved in fungi,
      all the peptide bonds of the phosphate binding loop are in trans conformation
      whereas in nonfungal 6-oxopurine PRTs, one cis-peptide bond is required for
      phosphate binding. Mutations affecting the enzyme activity or the previously
      characterized feedback inhibition by GMP are located at the nucleotide binding
      site and the dimer interface.

PMID- 22610486
TI  - An evolutionary view of plant tissue culture: somaclonal variation and selection.
AB  - Plants regenerated from in vitro cultures possess an array of genetic and
      epigenetic changes. This phenomenon is known as 'somaclonal variation' and the
      frequency of somaclonal variation (SV) is usually elevated far beyond that
      expected in nature. Initially, the relationship between time in culture and
      detected SV was found to support the widespread belief that SV accumulates with
      culture age. However, a few studies indicated that older cultures yielded
      regenerants with less SV. What leads to this seemed contradiction? In this
      article, we have proposed a novel in vitro callus selection hypothesis,
      differentiation bottleneck (D-bottleneck) and dedifferentiation bottleneck (Dd
      bottleneck), which consider natural selection theory to be fit for cell
      population in vitro. The results of multiplication races between the cells with
      the true-to-type phenotype and the deleterious cells determine the
      increase/decrease of SV frequencies in calli or regenerants as in vitro culture
      time goes on. The possibility of interpreting the complex situation of time
      related SV by the evolutionary theory is discussed in this paper. In addition,
      the SV threshold, space-determined hypothesis and D-bottleneck are proposed to
      interpret the loss of the regenerability through a long period of plant tissue
      culture (PTC).

PMID- 22610488
TI  - How special is sameness for pigeons and people?
AB  - Because of the importance of the sense of sameness for psychological science and
      because of the tenuous support for this notion in pigeons' matching-to-sample
      behavior, we experimentally explored the possibly special status of sameness for
      pigeons. Using photographs from three different natural categories (dogs, fish,
      and flowers) in a three-alternative matching-to-sample design, we obtained a
      reliable sameness advantage for pigeons only when the number of correct sample
      comparison combinations could have contributed to a sameness advantage;
      otherwise, no sameness advantage emerged. However, human participants exhibited
      an immediate and dramatic sameness advantage under essentially the same training
      and testing conditions as had been given to pigeons. At least under these
      experimental circumstances, humans exhibit a sameness advantage that far eclipses
      that of pigeons.

PMID- 22610487
TI  - A maize stress-responsive NAC transcription factor, ZmSNAC1, confers enhanced
      tolerance to dehydration in transgenic Arabidopsis.
AB  - NAC proteins are plant-specific transcription factors that play essential roles
      in stress responses. However, only little information regarding stress-related
      NAC genes is available in maize. In this study, a maize NAC gene, ZmSNAC1, was
      cloned and functionally characterized. Expression analysis revealed that ZmSNAC1
      was strongly induced by low temperature, high-salinity, drought stress, and
      abscisic acid (ABA) treatment, but downregulated by salicylic acid treatment.
      Subcellular localization experiments in Arabidopsis protoplast cells indicated
      that ZmSNAC1 was localized in the nucleus. Transactivation assays demonstrated
      that ZmSNAC1 functioned as a transcriptional activator. Overexpression of ZmSNAC1
      in Arabidopsis led to hypersensitivity to ABA and osmotic stress at the
      germination stage, but enhanced tolerance to dehydration compared to wild-type
      seedlings. These results suggest that ZmSNAC1 functions as a stress-responsive
      transcription factor in positive modulation of abiotic stress tolerance, and may
      have applications in the engineering of drought-tolerant crops. KEY MESSAGE:
      ZmSNAC1 functioned as a stress-responsive transcription factor in response to
      abiotic stresses, and might be useful for crop tolerance improvement.

PMID- 22610489
TI  - Pedunculated hamartomatous polyp of the appendix: report of a case.
AB  - We experienced a rare case of a pedunculated polyp of the appendix, which had
      been incidentally found by preventive appendectomy performed when providing
      surgical treatment for rectal carcinoma. A pathological investigation of this
      polypoid lesion demonstrated branches of fibro-muscular stalks connecting with
      the lamina muscularis covered by a hyperplastic mucosa, which proved to be
      consistent with the features of hamartoma. The patient had no external
      characteristics of Peutz-Jeghers syndrome, including mucocutaneous pigmentation
      and gastrointestinal polyposis, observed by endoscopy. This case is considered to
      be a Peutz-Jeghers type polyp of the appendix with a pedunculated form, which is
      very rare.

PMID- 22610490
TI  - Femoral head-neck offset measurements in 339 subjects: distribution and
      implications for femoroacetabular impingement.
AB  - PURPOSE: The alpha-angle is a frequently used measurement to quantify head-neck
      offset pathology in cam-type femoroacetabular impingement. However, diverging
      norm values and reference intervals have been described, especially in men.
      METHODS: The alpha-angle, the head-neck offset ratio and the triangular index
      were measured on anteroposterior and lateral radiographs of 339 (170 men and 169
      women) subjects without evident underlying hip pathology. RESULTS: For male
      subjects, the mean alpha-angle was 49.4 degrees  (SD 10.5 degrees ) on
      anteroposterior and 49.1 degrees  (SD 10.6 degrees ) on lateral radiographs,
      whereas for female subjects, it was 45.0 degrees  (SD 8.0 degrees ) and 46.1
      degrees  (SD 9.9 degrees ), respectively. Thus, calculated upper limits of
      reference intervals in the population screened were 70 degrees  for both
      radiographic projections in men and 61 degrees  (anteroposterior) and 66 degrees 
      (lateral) in women. CONCLUSION: These data substantiate recent findings that the
      pathological threshold of the alpha-angle in male subjects may be lower than that
      previously assumed. LEVEL OF EVIDENCE: Diagnostic, Level III.

PMID- 22610491
TI  - Dilated and unreactive pupils and burst-suppression on electroencephalography due
      to buproprion overdose.
AB  - Burst-suppression pattern on electroencephalography (EEG) occurs upon
      dissociation of the cortex from underlying brain structures. Unless the pattern
      is a physiologic consequence of administered sedatives, this
      electroencephalographic pattern is indicative of a poor neurologic outcome and
      high mortality. We report a case of a 29-year-old female thought to be brain dead
      based on initial physical examination and EEG findings of burst-suppression, who
      was later found to have supratherapeutic serum levels of bupropion. This is the
      second documented case of burst-suppression pattern on EEG in a patient who
      overdosed on bupropion. We propose that burst-suppression in the setting of
      bupropion toxicity may revert with drug clearance.

PMID- 22610492
TI  - Proposed glucocorticoid-mediated zinc signaling in the hippocampus.
AB  - Corticosteroid hormones are secreted from the adrenal glands in hourly pulses and
      signal the hippocampus for the development and function. In contrast, the stress
      induced rise in corticosteroid concentrations has a profound effect on emotional
      arousal, motivational processes and cognitive performance. This rise is required
      as the stress response to maintain homeostasis in the living body or restore it.
      However, abnormal rise in corticosteroid concentrations is a disadvantage to the
      hippocampus. Corticosteroid-glutamatergic interactions during information
      processing are proposed as a potential model to explain many of the diverse
      actions of corticosteroids in synaptic plasticity such as long-term potentiation
      and cognition. Because zincergic neurons are a subtype of glutamatergic neurons
      and release Zn(2+) and glutamate into the synaptic cleft, it is possible that
      homeostasis of synaptic Zn(2+), in addition to homeostasis of glutamate, is
      modified by glucocorticoids, followed by the changes in cognitive function and
      stress response. Zn(2+) signal participates in cognitive and emotional behavior
      in cooperation with signaling of glucocorticoids and glutamate, while can
      disadvantageously act on the hippocampus under sever stress circumstances. This
      paper analyzes the actions of glucocorticoid-mediated Zn(2+) signal in the
      hippocampus under stressful circumstances and its significance in both
      hippocampal function and dysfunction.

PMID- 22610493
TI  - A supervised framework for resolving coreference in clinical records.
AB  - OBJECTIVE: A method for the automatic resolution of coreference between medical
      concepts in clinical records. MATERIALS AND METHODS: A multiple pass sieve
      approach utilizing support vector machines (SVMs) at each pass was used to
      resolve coreference. Information such as lexical similarity, recency of a concept
      mention, synonymy based on Wikipedia redirects, and local lexical context were
      used to inform the method. Results were evaluated using an unweighted average of
      MUC, CEAF, and B(3) coreference evaluation metrics. The datasets used in these
      research experiments were made available through the 2011 i2b2/VA Shared Task on
      Coreference. RESULTS: The method achieved an average F score of 0.821 on the ODIE
      dataset, with a precision of 0.802 and a recall of 0.845. These results compare
      favorably to the best-performing system with a reported F score of 0.827 on the
      dataset and the median system F score of 0.800 among the eight teams that
      participated in the 2011 i2b2/VA Shared Task on Coreference. On the i2b2 dataset,
      the method achieved an average F score of 0.906, with a precision of 0.895 and a
      recall of 0.918 compared to the best F score of 0.915 and the median of 0.859
      among the 16 participating teams. DISCUSSION: Post hoc analysis revealed
      significant performance degradation on pathology reports. The pathology reports
      were characterized by complex synonymy and very few patient mentions. CONCLUSION:
      The use of several simple lexical matching methods had the most impact on
      achieving competitive performance on the task of coreference resolution.
      Moreover, the ability to detect patients in electronic medical records helped to
      improve coreference resolution more than other linguistic analysis.

PMID- 22610494
TI  - Method of electronic health record documentation and quality of primary care.
AB  - OBJECTIVE: Physicians who more intensively interact with electronic health
      records (EHRs) through their documentation style may pay greater attention to
      coded fields and clinical decision support and thus may deliver higher quality
      care. We measured the quality of care of physicians who used three predominating
      EHR documentation styles: dictation, structured documentation, and free text.
      METHODS: We conducted a retrospective analysis of visits by patients with
      coronary artery disease and diabetes to the Partners Primary Care Practice Based
      Research Network. The main outcome measures were 15 EHR-based coronary artery
      disease and diabetes measures assessed 30 days after primary care visits.
      RESULTS: During the 9-month study period, 7000 coronary artery disease and
      diabetes patients made 18 569 visits to 234 primary care physicians of whom 20
      (9%) predominantly dictated their notes, 68 (29%) predominantly used structured
      documentation, and 146 (62%) predominantly typed free text notes. In
      multivariable modeling adjusted for clustering by patient and physician, quality
      of care appeared significantly worse for dictators than for physicians using the
      other two documentation styles on three of 15 measures (antiplatelet medication,
      tobacco use documentation, and diabetic eye exam); better for structured
      documenters for three measures (blood pressure documentation, body mass index
      documentation, and diabetic foot exam); and better for free text documenters on
      one measure (influenza vaccination). There was no measure for which dictators had
      higher quality of care than physicians using the other two documentation styles.
      CONCLUSIONS: EHR-assessed quality is necessarily documentation-dependent, but
      physicians who dictated their notes appeared to have worse quality of care than
      physicians who used structured EHR documentation. CLINICAL TRIAL REGISTRATION
      NUMBER: ClinicalTrials.gov Identifier: NCT00235040.

PMID- 22610496
TI  - Association of anthropometric measures with SF-36v2 PCS and MCS in a multi-ethnic
      Asian population.
AB  - PURPOSE: Obesity adversely affects health-related quality of life (HRQoL). Most
      studies have used body mass index (BMI) to measure obesity. Other measures of
      obesity, such as waist circumference (WC) or waist-to-hip ratio (WHR), may be
      better predictors of cardiovascular disease and mortality. We, therefore,
      examined the associations between other anthropometric measures and HRQoL in a
      multi-ethnic Asian population. METHODS: In this follow-up study from four
      previous cross-sectional surveys, HRQoL was measured, at follow-up, using the
      Short-Form 36 version 2 (SF-36v2) questionnaire. Linear regression was used to
      assess the relationship between anthropometric measures [BMI, WC, waist residuals
      (WR) (generated by regressing WC on BMI), WHR, waist-to-height ratio (WHtR) and
      height (Ht)] and HRQoL. We compared the models' R2, Akaike's information criteria
      (AIC), and Schwarz Bayesian information criteria (BIC) from the different models.
      RESULTS: Among 4,981 subjects, 47.6% were men aged 50.6 +/- 12.2 and women aged
      49.3 +/- 11.6 years. All gender-specific anthropometric measures were
      significantly correlated with BMI, except WR. After adjusting for known
      determinants of HRQoL, we found significant associations between BMI, WC and WHtR
      with SF-36v2 Physical Component Summary (PCS) scores in women but not men. In
      contrast, after adjusting for known determinants of HRQoL, WR and WHR were
      significantly associated with SF-36v2 Mental component summary (MCS) scores in
      men, but not women. R2, AIC and BIC were similar for all anthropometric measures
      in the final model. CONCLUSIONS: The associations between measures of central
      obesity and HRQoL differed between men and women. In women, associations were
      seen with SF-36v2 PCS, but measures of central obesity did not have significant
      associations with HRQoL after controlling for BMI. In men, an association between
      WC and SF-36v2 MCS was statistically significant independent of BMI. These gender
      differences require further investigation.

PMID- 22610495
TI  - The Diabetes Telemonitoring Study Extension: an exploratory randomized comparison
      of alternative interventions to maintain glycemic control after withdrawal of
      diabetes home telemonitoring.
AB  - BACKGROUND: Telemonitoring interventions featuring transmission of home glucose
      records to healthcare providers have resulted in improved glycemic control in
      patients with diabetes. No research has addressed the intensity or duration of
      telemonitoring required to sustain such improvements. PURPOSE: The DiaTel study
      (10 January 2005 to 1 November 2007) compared active care management (ACM) with
      home telemonitoring (n=73) to monthly care coordination (CC) telephone calls
      (n=77) among veterans with diabetes and suboptimal glycemic control. The purpose
      of the DiaTel Extension was to assess whether initial improvements could be
      sustained with interventions of the same or lower intensity among participants
      who re-enrolled in a 6-month extension of DiaTel. METHODS: DiaTel participants
      receiving ACM were re-assigned randomly to monthly CC calls with continued
      telemonitoring but no active medication management (ACM-to-CCHT, n=23) or monthly
      CC telephone calls (ACM-to-CC, n=21). DiaTel participants receiving CC were re
      assigned randomly to continued CC (CC-to-CC, n=28) or usual care (UC, ie, CC-to
      UC, n=29). Hemaglobin A1c (HbA1c) was assessed at 3 and 6 months following re
      randomization. RESULTS: Marked HbA1c improvements observed in DiaTel ACM
      participants were sustained 6 months after re-randomization in both ACM-to-CCHT
      and ACM-to-CC groups. Lesser HbA1c improvements observed in DiaTel CC
      participants were sustained in both CC-to-CC and CC-to-UC groups. No benefit was
      apparent for continued transmission of glucose data among DiaTel ACM participants
      or continued monthly telephone calls among DiaTel CC participants 6 months after
      re-randomization. CONCLUSION: Significant improvements in HbA1c achieved using
      home telemonitoring and active medication management for 6 months were sustained
      6 months later with interventions of decreased intensity in VA Health System
      qualified veterans.   CLINICAL TRIAL REG. NO:  NCT00245882,
      http://www.clinicaltrials.gov.

PMID- 22610497
TI  - Importance of RNA stabilization: evaluation of ansB, ggt, and rpoA transcripts in
      microaerophilic Campylobacter jejuni 81-176.
AB  - A subset of food-borne Campylobacter jejuni strains utilizes amino acids
      asparagine and glutamine as carbon sources that may enhance the ability of this
      microaerophilic pathogen to colonize specific tissues. In this study, we analyzed
      the transcript sizes of the ansB and ggt genes encoding the periplasmic
      asparaginase and gamma-glutamyltranspeptidase in C. jejuni 81-176, respectively,
      and compared the expression level of mRNAs at different time points during the
      growth in vitro. In addition, we included the housekeeping rpoA gene, encoding
      the alpha-subunit of DNA-directed RNA polymerase, to monitor sample processing as
      it has been described as a stable reference gene in gene expression studies in C.
      jejuni. Our results revealed that both the ansB and ggt genes were expressed in
      the end of the logarithmic growth phase and their corresponding monocistronic
      mRNAs were not affected by sample processing steps. In contrast, the mRNAs of the
      polycistronic operon containing rpoA gene were highly induced at earlier stage of
      the logarithmic growth and were clearly differentially responding to external
      factors during cell harvesting step.

PMID- 22610498
TI  - Effects of Topiramate on afferent visual pathways: controversies and
      uncertainties.

PMID- 22610499
TI  - Discrete progression of migraine-induced focal cerebral infarction.

PMID- 22610500
TI  - Benefits and harms of CT screening for lung cancer: a systematic review.
AB  - CONTEXT: Lung cancer is the leading cause of cancer death. Most patients are
      diagnosed with advanced disease, resulting in a very low 5-year survival.
      Screening may reduce the risk of death from lung cancer. OBJECTIVE: To conduct a
      systematic review of the evidence regarding the benefits and harms of lung cancer
      screening using low-dose computed tomography (LDCT). A multisociety collaborative
      initiative (involving the American Cancer Society, American College of Chest
      Physicians, American Society of Clinical Oncology, and National Comprehensive
      Cancer Network) was undertaken to create the foundation for development of an
      evidence-based clinical guideline. DATA SOURCES: MEDLINE (Ovid: January 1996 to
      April 2012), EMBASE (Ovid: January 1996 to April 2012), and the Cochrane Library
      (April 2012). STUDY SELECTION: Of 591 citations identified and reviewed, 8
      randomized trials and 13 cohort studies of LDCT screening met criteria for
      inclusion. Primary outcomes were lung cancer mortality and all-cause mortality,
      and secondary outcomes included nodule detection, invasive procedures, follow-up
      tests, and smoking cessation. DATA EXTRACTION: Critical appraisal using
      predefined criteria was conducted on individual studies and the overall body of
      evidence. Differences in data extracted by reviewers were adjudicated by
      consensus. RESULTS: Three randomized studies provided evidence on the effect of
      LDCT screening on lung cancer mortality, of which the National Lung Screening
      Trial was the most informative, demonstrating that among 53,454 participants
      enrolled, screening resulted in significantly fewer lung cancer deaths (356 vs
      443 deaths; lung cancer-specific mortality, 274 vs 309 events per 100,000 person
      years for LDCT and control groups, respectively; relative risk, 0.80; 95% CI,
      0.73-0.93; absolute risk reduction, 0.33%; P = .004). The other 2 smaller studies
      showed no such benefit. In terms of potential harms of LDCT screening, across all
      trials and cohorts, approximately 20% of individuals in each round of screening
      had positive results requiring some degree of follow-up, while approximately 1%
      had lung cancer. There was marked heterogeneity in this finding and in the
      frequency of follow-up investigations, biopsies, and percentage of surgical
      procedures performed in patients with benign lesions. Major complications in
      those with benign conditions were rare. CONCLUSION: Low-dose computed tomography
      screening may benefit individuals at an increased risk for lung cancer, but
      uncertainty exists about the potential harms of screening and the
      generalizability of results.

PMID- 22610501
TI  - A functional trinucleotide repeat polymorphism in the 5'-untranslated region of
      the glutathione biosynthetic gene GCLC is associated with increased risk for lung
      and aerodigestive tract cancers.
AB  - Glutathione (GSH), the major intracellular antioxidant, protects against cancer
      development by detoxifying carcinogens and free radicals and strengthening the
      immune system. Recently, a GAG-trinucleotide repeat polymorphism in the 5'
      untranslated region of the gene for the rate-limiting enzyme for GSH
      biosynthesis, gamma-glutamine cysteine ligase (GCL), was shown to be associated
      with lowered GCL activity and GSH levels in vitro and in vivo. We tested the
      hypothesis that this functional polymorphism in GCL is associated with the risk
      for lung and aerodigestive tract cancers. To this end, we conducted a case
      control study that included 375 lung cancer cases, 200 aerodigestive tract cancer
      cases, and 537 controls. GAG repeat genotype (4, 7, 8, 9, and 10 repeat alleles)
      was determined by capillary electrophoresis of PCR products from the repeat
      region of the GCL catalytic subunit (GCLC). Odds ratios (OR) were calculated by
      logistic regression and adjusted for risk factors, including age, sex, body mass
      index, and smoking history. The GAG-7/7 genotype was associated with a 1.9-fold
      increased risk of lung cancer and 2.6-fold increased risk of aerodigestive tract
      cancer compared to the wild-type GAG-9/9 (P < 0.05). Similarly, the GAG-7 allele
      was associated with an increased risk of lung cancer (OR = 1.5, P = 0.01) and
      aerodigestive tract cancer (OR = 2.3, P < 0.001) compared to subjects without GAG
      7 allele. These findings suggest that GSH synthesis affects the risk of lung and
      aerodigestive tract cancers, and further implicates a role for oxidative stress
      in the development of these cancers.

PMID- 22610502
TI  - Genome-wide analysis of polymorphisms associated with cytokine responses in
      smallpox vaccine recipients.
AB  - The role that genetics play in response to infection or disease is becoming
      increasingly clear as we learn more about immunogenetics and host-pathogen
      interactions. Here we report a genome-wide analysis of the effects of host
      genetic variation on cytokine responses to vaccinia virus stimulation in smallpox
      vaccine recipients. Our data show that vaccinia stimulation of immune individuals
      results in secretion of inflammatory and Th1 cytokines. We identified multiple
      SNPs significantly associated with variations in cytokine secretion. These SNPs
      are found in genes with known immune function, as well as in genes encoding for
      proteins involved in signal transduction, cytoskeleton, membrane channels and ion
      transport, as well as others with no previously identified connection to immune
      responses. The large number of significant SNP associations implies that cytokine
      secretion in response to vaccinia virus is a complex process controlled by
      multiple genes and gene families. Follow-up studies to replicate these findings
      and then pursue mechanistic studies will provide a greater understanding of how
      genetic variation influences vaccine responses.

PMID- 22610504
TI  - An efficient and high-throughput protocol for Agrobacterium-mediated
      transformation based on phosphomannose isomerase positive selection in Japonica
      rice (Oryza sativa L.).
AB  - A number of Agrobacterium-mediated rice transformation systems have been
      developed and widely used in numerous laboratories and research institutes.
      However, those systems generally employ antibiotics like kanamycin and
      hygromycin, or herbicide as selectable agents, and are used for the small-scale
      experiments. To address high-throughput production of transgenic rice plants via
      Agrobacterium-mediated transformation, and to eliminate public concern on
      antibiotic markers, we developed a comprehensive efficient protocol, covering
      from explant preparation to the acquisition of low copy events by real-time PCR
      analysis before transplant to field, for high-throughput production of transgenic
      plants of Japonica rice varieties Wanjing97 and Nipponbare using Escherichia coli
      phosphomannose isomerase gene (pmi) as a selectable marker. The transformation
      frequencies (TF) of Wanjing97 and Nipponbare were achieved as high as 54.8 and
      47.5%, respectively, in one round of selection of 7.5 or 12.5 g/L mannose
      appended with 5 g/L sucrose. High-throughput transformation from inoculation to
      transplant of low copy events was accomplished within 55-60 days. Moreover, the
      Taqman assay data from a large number of transformants showed 45.2% in Wanjing97
      and 31.5% in Nipponbare as a low copy rate, and the transformants are fertile and
      follow the Mendelian segregation ratio. This protocol facilitates us to perform
      genome-wide functional annotation of the open reading frames and utilization of
      the agronomically important genes in rice under a reduced public concern on
      selectable markers. KEY MESSAGE: We describe a comprehensive protocol for large
      scale production of transgenic Japonica rice plants using non-antibiotic
      selectable agent, at simplified, cost- and labor-saving manners.

PMID- 22610505
TI  - How to investigate and treat: migraine in patients with temporomandibular
      disorders.
AB  - Migraine and temporomandibular disorders (TMD) are highly prevalent conditions
      that frequently coexist in the same patient. The relationship between migraine
      and TMD is complex. Migraineurs often have pain in the TMD area; TMD sufferers,
      in turn, often experience headaches in addition to the pain in the jaw. Finally,
      migraine and TMD are comorbid, and the final phenotype of patients with the
      comorbidity may represent the aggregated contribution of both. Herein we briefly
      discuss the clinical commonalities of migraine and TMD, and the differential
      diagnosis of these conditions with other causes of facial pain. We close by
      presenting our experience in the treatment of patients with the comorbidity.

PMID- 22610506
TI  - Spinal cord stimulation in the treatment of cancer-related pain: "back to the
      origins".
AB  - Spinal cord stimulation (SCS) has been used in the treatment of chronic pain for
      more than 40 years. The most common indication for SCS in the USA is failed back
      surgery syndrome (FBSS). Interestingly, the first two spinal cord stimulators
      ever implanted were in patients suffering from bronchogenic carcinoma and pelvic
      cancer, respectively. While cancer accounts for millions of deaths each year in
      the USA, pain is often the first sign of malignancy. An increasing number of
      people suffer from cancer-related pain each year and many receive suboptimal
      relief. Given the demonstrated value of spinal cord stimulation in the treatment
      of neuropathic pain, spinal cord stimulation should be considered "earlier" as an
      adjunct to the treatment of cancer-related pain. In addition, with the improving
      survival rates associated with advances in cancer treatment, spinal cord
      stimulation may help reduce the risk of development of chronic neuropathic pain
      in survivors.

PMID- 22610507
TI  - Trigger point needling: techniques and outcome.
AB  - In this review we provide the updates on last years' advancements in basic
      science, imaging methods, efficacy, and safety of dry needling of myofascial
      trigger points (MTrPs). The latest studies confirmed that dry needling is an
      effective and safe method for the treatment of MTrPs when provided by adequately
      trained physicians or physical therapists. Recent basic studies have confirmed
      that at the site of an active MTrP there are elevated levels of inflammatory
      mediators, known to be associated with persistent pain states and myofascial
      tenderness and that this local milieu changes with the occurrence of local twitch
      response. Two new modalities, sonoelastography and magnetic resonance
      elastography, were recently introduced allowing noninvasive imaging of MTrPs.
      MTrP dry needling, at least partially, involves supraspinal pain control via
      midbrain periaqueductal gray matter activation. A recent study demonstrated that
      distal muscle needling reduces proximal pain by means of the diffuse noxious
      inhibitory control. Therefore, in a patient too sensitive to be needled in the
      area of the primary pain source, the treatment can be initiated with distal
      needling.

PMID- 22610508
TI  - A conditional allele of Rspo3 reveals redundant function of R-spondins during
      mouse limb development.
AB  - R-spondins are secreted ligands that bind cell surface receptors and activate
      Wnt/beta-catenin signaling. Human mutations and gene inactivation studies in mice
      have revealed a role for these four proteins (RSPO1-4) in diverse developmental
      processes ranging from sex determination to limb development. Among the genes
      coding for R-spondins, only inactivation of Rspo3 shows early embryonic lethality
      (E10.5 in mice). Therefore, a conditional allele of this gene is necessary to
      understand the function of R-spondins throughout murine development. To address
      this need, we have produced an allele in which loxP sites flank exons 2-4 of
      Rspo3, allowing tissue-specific deletion of these exons in the presence of Cre
      recombinase. We used these mice to investigate the role of Rspo3 during limb
      development and found that limbs ultimately developed normally in the absence of
      Rspo3 function. However, severe hindlimb truncations resulted when Rspo3 and
      Rspo2 mutations were combined, demonstrating redundant function of these genes.

PMID- 22610509
TI  - Post-traumatic transdiaphragmatic intercostal hernia: report of two cases.
AB  - Transdiaphragmatic intercostal hernias (TIH) are rare. Less than 40 cases of TIH
      have so far been reported, with only 8 cases involving herniation of the liver.
      This report presents the case of 2 patients with a right-sided abdominal lump
      following a fall. Thoracoabdominal CT-scan showed a TIH between the 9th and 10th
      ribs with liver and right colonic herniation in both patients. Both patients were
      successfully treated with mesh repair. The presentation, physiopathology and
      management of this rare occurrence are discussed.

PMID- 22610510
TI  - Calcium control of triphasic hippocampal STDP.
AB  - Synaptic plasticity is believed to represent the neural correlate of mammalian
      learning and memory function. It has been demonstrated that changes in synaptic
      conductance can be induced by approximately synchronous pairings of pre- and post
      synaptic action potentials delivered at low frequencies. It has also been
      established that NMDAr-dependent calcium influx into dendritic spines represents
      a critical signal for plasticity induction, and can account for this spike-timing
      dependent plasticity (STDP) as well as experimental data obtained using other
      stimulation protocols. However, subsequent empirical studies have delineated a
      more complex relationship between spike-timing, firing rate, stimulus duration
      and post-synaptic bursting in dictating changes in the conductance of hippocampal
      excitatory synapses. Here, we present a detailed biophysical model of single
      dendritic spines on a CA1 pyramidal neuron, describe the NMDAr-dependent calcium
      influx generated by different stimulation protocols, and construct a parsimonious
      model of calcium driven kinase and phosphatase dynamics that dictate the
      probability of stochastic transitions between binary synaptic weight states in a
      Markov model. We subsequently demonstrate that this approach can account for a
      range of empirical observations regarding the dynamics of synaptic plasticity
      induced by different stimulation protocols, under regimes of pharmacological
      blockade and metaplasticity. Finally, we highlight the strengths and weaknesses
      of this parsimonious, unified computational synaptic plasticity model, discuss
      differences between the properties of cortical and hippocampal plasticity
      highlighted by the experimental literature, and the manner in which further
      empirical and theoretical research might elucidate the cellular basis of
      mammalian learning and memory function.

PMID- 22610511
TI  - Human adipose tissue-derived stem cells protect impaired cardiomyocytes from
      hypoxia/reoxygenation injury through hypoxia-induced paracrine mechanism.
AB  - Growing studies have emerged on adipose-derived stem cells (ADSCs), which hold
      the potential for cell-based therapy in diseased injured hearts. Apart from their
      differentiation pluripotency, such benefits also result from the ability of
      paracrine. The results of this study showed that after a 24-h hypoxia culture,
      ADSCs secreted amplified quantities of hepatocyte growth factor, interleukin-1,
      vascular endothelial growth factor-A, fibroblast growth factor-2, and
      transforming growth factor-beta, all of which increased statistically compared
      with normoxia cultures. Resultantly, conditioned media (CM) from hypoxia-treated
      ADSCs can promptly improve cardiac function in in vivo infarction model as well
      as ameliorate apoptosis of cardiomyocytes subjected to hypoxia/reoxygenation
      conditions, accompanied by changes of JNK signal activation. While SP600125, a
      specific JNK pathway inhibitor, partly decreased cardiac cytoprotection assessed
      by incremental caspase-3 activation and subsequent TUNEL index, which led to no
      significantly different outcome between CM from ADSCs in normoxia culture and
      those in hypoxia culture. These data suggested that, in response to hypoxia,
      ADSCs could amplify expression of several protective soluble factors, which
      mediate direct cytoprotection. Furthermore, the improvement for impaired
      cardiomyocytes treated by hypoxia-induced ADSCs-CM was significant in part
      because of the involvement of the JNK signal pathway.

PMID- 22610512
TI  - Comprehensive therapeutic outcomes of frontline imatinib mesylate in newly
      diagnosed chronic phase chronic myeloid leukemia patients in Korea: feasibility
      assessment of current ELN recommendation.
AB  - Optimal responses during imatinib therapy are commonly defined following the
      European LeukemiaNet (ELN) recommendations. Achievements of these optimal
      responses have not, however, been comprehensively tested as response-related
      prognostic factors using single center data sets. We evaluated the parameters
      using long-term (median 63 months) outcomes from 363 chronic phase chronic
      myeloid leukemia patients treated with imatinib as frontline therapy at our
      center. Intention-to-treat analysis showed comparable rates of complete
      cytogenetic response (86 %), major molecular response (MMR, 54 %), and complete
      molecular response (MR(4.5), 8 %). Estimated overall survival, progression-free
      survival, and event-free survival at 7 years were 94, 88 and 84 %, respectively.
      Achievement of recommended optimal response at 6 months (major cytogenetic
      response) and 12 months (complete cytogenetic response) yielded significantly
      better overall, progression-free, and event-free survival. However, achievement
      of recommended optimal response at 18 months (MMR) provided marginal benefit only
      in event-free survival. Most ELN criteria were predictive of long-term outcomes,
      with the exception of the clinical significance of achieving MMR at 18 months.
      Treatment adherence in the early treatment period was one of the important
      independent predictors of favorable long-term outcome. Durable cytogenetic and
      molecular responses were maintained in a majority of patients treated with
      optimal dose intensity.

PMID- 22610514
TI  - Genetic and environmental etiology of nicotine use in Sri Lankan male twins.
AB  - Little is known about the prevalence and etiology of tobacco use in Asian
      populations. This study aims to test whether the finding of substantial
      heritability for tobacco-related phenotypes in Western populations is
      generalizable to developing countries. The twin method was used to estimate the
      relative contribution of genetic and environmental influences on nicotine-related
      phenotypes. Participants were selected from the population based Sri Lankan Twin
      Registry. The Composite International Diagnostic Interview was administered to
      1,804 male individuals to assess five phenotypes: nicotine use; desire and
      unsuccessful attempts to quit smoking; subjective feeling of being tobacco
      dependent; and two DSM-IV diagnoses; nicotine dependence and nicotine withdrawal.
      Almost one-third of the male twins were life-time smokers. The genetic results
      were consistent with the previously reported findings from Western and Chinese
      populations, in that the nicotine use traits were significantly heritable, with
      environmental influences being of the non-shared nature. The results derived from
      the Causal Contingent Common pathway model (CCC) supported previous findings that
      show that liabilities to regular smoking and subsequent problem smoking have both
      shared and specific genetic influences.

PMID- 22610515
TI  - Strategies for membrane interaction proteomics: no mass spectrometry required.
AB  - Membrane-bound proteins are one of the most important protein types in the cell,
      and are involved in many major cell processes and signaling pathways. Most
      proteins, including those at membranes, must interact with other proteins to form
      complexes, which are essential for their function(s). In this review, we describe
      some of the major non-mass spectrometry-based methods and technologies used for
      the investigation of intracellular membrane protein complexes including Tango,
      fluorescence/bioluminescence resonance energy transfer (F/BRET), luminescence
      based mammalian interactome mapping (LUMIER), protein-fragment complementation
      assay (PCA), and membrane yeast two-hybrid assay (MYTH). We highlight the
      advantages and drawbacks of these methods, describe recent studies utilizing
      these methods, and discuss some of the major findings in the study of membrane
      protein-based cell pathways.

PMID- 22610516
TI  - Curtailment in single-arm two-stage phase II oncology trials.
AB  - Two-stage designs that allow for early stopping if the treatment is ineffective
      are commonly used in phase II oncology trials. A limitation of current designs is
      that early stopping is only allowed at the end of the first stage, even if it
      becomes evident during the trial that a significant result is unlikely. One way
      to overcome this limitation is to implement stochastic curtailment procedures
      that enable stopping the trial whenever the conditional power is below a pre
      specified threshold theta. In this paper, we present the results for implementing
      curtailment rules in either only the second stage or both stages of the designs.
      In total, 102 scenarios with different parameter settings were investigated using
      conditional power thresholds theta between 0 and 1 in steps of 0.01. An increase
      in theta results not only in a decrease of the actual Type I error rate and power
      but also of the expected sample size. Therefore, a reasonable balance has to be
      found when selecting a specific threshold value in the planning phase of a
      curtailed two-stage design. Given that the effect of curtailment highly depends
      on the underlying design parameters, no general recommendation for theta can be
      made. However, up to theta=0.2, the loss in power was less than 5% for all
      investigated scenarios while savings of up to 50% in expected sample size
      occurred. In general, curtailment is most appropriate when the outcome can be
      observed fast or when accrual is slow so that adequate information for making
      early and frequent decisions is available.

PMID- 22610513
TI  - The five factors of personality and regional cortical variability in the
      Baltimore longitudinal study of aging.
AB  - Although personality changes have been associated with brain lesions and atrophy
      caused by neurodegenerative diseases and aging, neuroanatomical correlates of
      personality in healthy individuals and their stability over time have received
      relatively little investigation. In this study, we explored regional gray matter
      (GM) volumetric associations of the five-factor model of personality. Eighty
      seven healthy older adults took the NEO Personality Inventory and had brain MRI
      at two time points 2 years apart. We performed GM segmentation followed by
      regional analysis of volumes examined in normalized space map creation and voxel
      based morphometry-type statistical inference in SPM8. We created a regression
      model including all five factors and important covariates. Next, a conjunction
      analysis identified associations between personality scores and GM volumes that
      were replicable across time, also using cluster-level Family-Wise-Error
      correction. Larger right orbitofrontal and dorsolateral prefrontal cortices and
      rolandic operculum were associated with lower Neuroticism; larger left temporal,
      dorsolateral prefrontal, and anterior cingulate cortices with higher
      Extraversion; larger right frontopolar and smaller orbitofrontal and insular
      cortices with higher Openness; larger right orbitofrontal cortex with higher
      Agreeableness; larger dorsolateral prefrontal and smaller frontopolar cortices
      with higher Conscientiousness. In summary, distinct personality traits were
      associated with stable individual differences in GM volumes. As expected for
      higher-order traits, regions performing a large number of cognitive and affective
      functions were implicated. Our findings highlight personality-related variation
      that may be related to individual differences in brain structure that merit
      additional attention in neuroimaging research.

PMID- 22610517
TI  - Understanding the dehydration of levofloxacin hemihydrate.
AB  - Levofloxacin is a broad-spectrum antibiotic that exists as a hemihydrate under
      ambient conditions. In addition to the hemihydrate, there are three known
      crystalline anhydrate forms, denoted as alpha, beta, and gamma. In this study,
      differential scanning calorimetry (DSC), thermogravimetric analysis, Raman
      spectroscopy, single-crystal and powder X-ray diffraction, and solid-state NMR
      spectroscopy were used to investigate the transitions that occurred upon
      dehydration to the anhydrate as well as additional transitions that occurred to
      the anhydrous material upon heating/cooling. An enantiotropic conversion was
      observed in the DSC around 54 degrees C corresponding to the conversion of the
      gamma form to a new form, denoted as the delta form. Raman spectroscopy, powder X
      ray diffraction, and solid-state NMR spectroscopy confirmed that a new
      crystalline form was being produced.

PMID- 22610518
TI  - Cucurbit[7]uril encapsulated cisplatin overcomes cisplatin resistance via a
      pharmacokinetic effect.
AB  - The cucurbit[n]uril (CB[n]) family of macrocycles has been shown to have
      potential in drug delivery where they are able to provide physical and chemical
      stability to drugs, improve drug solubility, control drug release and mask the
      taste of drugs. Cisplatin is a small molecule platinum-based anticancer drug that
      has severe dose-limiting side-effects. Cisplatin forms a host-guest complex with
      cucurbit[7]uril (cisplatin@CB[7]) with the platinum atom and both chlorido
      ligands located inside the macrocycle, with binding stabilised by four hydrogen
      bonds (2.15-2.44 A). Whilst CB[7] has no effect on the in vitro cytotoxicity of
      cisplatin in the human ovarian carcinoma cell line A2780 and its cisplatin
      resistant sub-lines A2780/cp70 and MCP1, there is a significant effect on in vivo
      cytotoxicity using human tumour xenografts. Cisplatin@CB[7] is just as effective
      on A2780 tumours compared with free cisplatin, and in the cisplatin-resistant
      A2780/cp70 tumours cisplatin@CB[7] markedly slows tumour growth. The ability of
      cisplatin@CB[7] to overcome resistance in vivo appears to be a pharmacokinetic
      effect. Whilst the peak plasma level and tissue distribution are the same for
      cisplatin@CB[7] and free cisplatin, the total concentration of circulating
      cisplatin@CB[7] over a period of 24 hours is significantly higher than for free
      cisplatin when administered at the equivalent dose. The results provide the first
      example of overcoming drug resistance via a purely pharmacokinetic effect rather
      than drug design or better tumour targeting, and demonstrate that in vitro assays
      are no longer as important in screening advanced systems of drug delivery.

PMID- 22610519
TI  - The epidemiology, morbidity, and outcome of soccer-related fractures in a
      standard population.
AB  - BACKGROUND: Soccer is the most common cause of sporting fracture, but little is
      known about patient outcome after such fractures. PURPOSE: To describe the
      epidemiological characteristics of soccer-related fractures, their outcomes, and
      the likelihood of return to soccer after injury in a known United Kingdom
      population at all skill levels. STUDY DESIGN: Descriptive epidemiology study.
      METHODS: All soccer fractures during 2007-2008 in the Lothian population were
      prospectively collected, with the diagnosis confirmed by an orthopaedic surgeon
      when patients attended the only adult orthopaedic service in Lothian. Patients
      living outside the region were excluded from the study. Patients were contacted
      in August 2010 to ascertain their progress in returning to soccer. RESULTS: A
      total of 367 fractures were recorded over the study period in 357 patients; 312
      fractures (85%) in 303 patients (85%) were followed up, with a mean interval of
      30 months (range, 24-36 months). The mean time for return to soccer from injury
      was 15 +/- 17 weeks (range, 0-104 weeks). For patients with lower limb injuries,
      the mean time was 26 +/- 22 weeks (range, 4-104 weeks) compared with 9 +/- 8
      weeks for patients with upper limb injuries (range, 0-64 weeks). Fourteen percent
      of the whole cohort did not return to soccer; 83% returned to soccer at the same
      level or higher. Thirty-nine percent had ongoing related problems; however, only
      8% had impaired soccer ability because of these problems. Fractures with the
      highest morbidity in not returning to soccer were to the clavicle (24%), distal
      radius (21%), and tibial diaphysis (20%). CONCLUSION: Most patients sustaining a
      fracture while playing soccer will return to soccer at a similar level. While
      over one third of them will have persisting symptoms 2 years after injury, for
      the majority, this will not impair their soccer ability.

PMID- 22610520
TI  - Effect of an indwelling pleural catheter vs chest tube and talc pleurodesis for
      relieving dyspnea in patients with malignant pleural effusion: the TIME2
      randomized controlled trial.
AB  - CONTEXT: Malignant pleural effusion causes disabling dyspnea in patients with a
      short life expectancy. Palliation is achieved by fluid drainage, but the most
      effective first-line method has not been determined. OBJECTIVE: To determine
      whether indwelling pleural catheters (IPCs) are more effective than chest tube
      and talc slurry pleurodesis (talc) at relieving dyspnea. DESIGN: Unblinded
      randomized controlled trial (Second Therapeutic Intervention in Malignant
      Effusion Trial [TIME2]) comparing IPC and talc (1:1) for which 106 patients with
      malignant pleural effusion who had not previously undergone pleurodesis were
      recruited from 143 patients who were treated at 7 UK hospitals. Patients were
      screened from April 2007-February 2011 and were followed up for a year.
      INTERVENTION: Indwelling pleural catheters were inserted on an outpatient basis,
      followed by initial large volume drainage, education, and subsequent home
      drainage. The talc group were admitted for chest tube insertion and talc for
      slurry pleurodesis. MAIN OUTCOME MEASURE: Patients completed daily 100-mm line
      visual analog scale (VAS) of dyspnea over 42 days after undergoing the
      intervention (0 mm represents no dyspnea and 100 mm represents maximum dyspnea;
      10 mm represents minimum clinically significant difference). Mean difference was
      analyzed using a mixed-effects linear regression model adjusted for minimization
      variables. RESULTS: Dyspnea improved in both groups, with no significant
      difference in the first 42 days with a mean VAS dyspnea score of 24.7 in the IPC
      group (95% CI, 19.3-30.1 mm) and 24.4 mm (95% CI, 19.4-29.4 mm) in the talc
      group, with a difference of 0.16 mm (95% CI, -6.82 to 7.15; P = .96). There was a
      statistically significant improvement in dyspnea in the IPC group at 6 months,
      with a mean difference in VAS score between the IPC group and the talc group of 
      14.0 mm (95% CI, -25.2 to -2.8 mm; P = .01). Length of initial hospitalization
      was significantly shorter in the IPC group with a median of 0 days (interquartile
      range [IQR], 0-1 day) and 4 days (IQR, 2-6 days) for the talc group, with a
      difference of -3.5 days (95% CI, -4.8 to -1.5 days; P < .001). There was no
      significant difference in quality of life. Twelve patients (22%) in the talc
      group required further pleural procedures compared with 3 (6%) in the IPC group
      (odds ratio [OR], 0.21; 95% CI, 0.04-0.86; P = .03). Twenty-one of the 52
      patients in the catheter group experienced adverse events vs 7 of 54 in the talc
      group (OR, 4.70; 95% CI, 1.75-12.60; P = .002). CONCLUSION: Among patients with
      malignant pleural effusion and no previous pleurodesis, there was no significant
      difference between IPCs and talc pleurodesis at relieving patient-reported
      dyspnea. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN87514420.

PMID- 22610522
TI  - LY2033298, a positive allosteric modulator at muscarinic M4 receptors, enhances
      inhibition by oxotremorine of light-induced phase shifts in hamster circadian
      activity rhythms.
AB  - RATIONALE: Entrainment of circadian rhythms to the light-dark cycle is essential
      for restorative sleep, and abnormal sleep timing is implicated in central nervous
      system (CNS) disorders like depression, schizophrenia, and Alzheimer's disease.
      Many transmitters, including acetylcholine, that exerts its actions via
      muscarinic receptors modulate the suprachiasmatic nucleus, the master pacemaker.
      OBJECTIVES: Since positive allosteric modulators of muscarinic M(4) receptors are
      candidates for treatment of mood and cognitive deficits of CNS disorders, it is
      important to evaluate their circadian actions. MATERIALS AND METHODS: The effects
      of intraperitoneally applied muscarinic agents on circadian wheel-running rhythms
      were measured employing hamsters, a model organism for studying activity rhythms.
      RESULTS: Systemic administration of the muscarinic receptor agonist oxotremorine
      (0.01-0.04 mg/kg) inhibited light-induced phase delays and advances of hamster
      circadian wheel-running rhythms. The M4 positive allosteric modulator, LY2033298
      (10-40 mg/kg), had no effect on light-induced phase shifts when administered
      alone, yet significantly enhanced (at 20 mg/kg) the inhibitory influence of
      oxotremorine on light-induced phase delays. In addition, the muscarinic receptor
      antagonist, scopolamine, which was without effect on light-induced phase shifts
      when administered alone (0.001-0.1 mg/kg), antagonized (at 0.1 mg/kg) the
      inhibitory effect of oxotremorine and LY2033298 on light-induced phase delays.
      CONCLUSIONS: These results are the first to demonstrate that systemically applied
      muscarinic receptor agonists modulate circadian activity rhythms, and they also
      reveal a specific role for M4 receptors. It will be of importance to evaluate
      circadian actions of psychotropic drugs acting via M4 receptors, since they may
      display beneficial properties under pathological conditions.

PMID- 22610521
TI  - Chronic psychosocial stress and citalopram modulate the expression of the glial
      proteins GFAP and NDRG2 in the hippocampus.
AB  - RATIONALE: It has been suggested that there are causal relationships between
      alterations in brain glia and major depression. OBJECTIVES: To investigate
      whether a depressive-like state induces changes in brain astrocytes, we used
      chronic social stress in male rats, an established preclinical model of
      depression. Expression of two astrocytic proteins, the intermediate filament
      component glial fibrillary acidic protein (GFAP) and the cytoplasmic protein N
      myc downregulated gene 2 (NDRG2), was analyzed in the hippocampus. For
      comparison, expression of the neuronal protein syntaxin-1A was also determined.
      METHODS: Adult male rats were subjected to daily social defeat for 5 weeks and
      were concomitantly treated with citalopram (30 mg/kg/day, via the drinking water)
      for 4 weeks. RESULTS: Western blot analysis showed that the chronic stress
      downregulated GFAP but upregulated NDRG2 protein. Citalopram did not prevent
      these stress effects, but the antidepressant per se downregulated GFAP and
      upregulated NDRG2 in nonstressed rats. In contrast, citalopram prevented the
      stress-induced upregulation of the neuronal protein syntaxin-1A. CONCLUSIONS:
      These data suggest that chronic stress and citalopram differentially affect
      expression of astrocytic genes while the antidepressant drug does not prevent the
      stress effects. The inverse regulation of the cytoskeletal protein GFAP and the
      cytoplasmic protein NDRG2 indicates that the cells undergo profound metabolic
      changes during stress and citalopram treatment. Furthermore, the present findings
      indicate that a 4-week treatment with citalopram does not restore normal glial
      function in the hippocampus, although the behavior of the animals was normalized
      within this treatment period, as reported previously.

PMID- 22610523
TI  - A versatile Agrobacterium-mediated transient gene expression system for
      herbaceous plants and trees.
AB  - Plant transient expression is a powerful method used widely for the functional
      characterization of genes and protein production. In comparison with stable
      transformation, it has the advantages of being simple, quick, economical, and
      effective. In the present study, we developed a novel transient gene expression
      system based on Agrobacterium-mediated transformation. This system is simple and
      convenient and allows for high transient expression levels. Hyperosmotic
      pretreatment of plants significantly improved the transient expression in this
      system. Furthermore, other factors, including acetosyringone concentration,
      cocultivation time, and Agrobacterium cell density, significantly influenced
      transient expression efficiency. The results showed that this method is suitable
      for use with herbaceous plants (such as tobacco and Arabidopsis) and trees (such
      as birch, poplar, tamarisk, cork, willow, and aralia), suggesting that it may be
      applied widely in plant transient expression studies.

PMID- 22610524
TI  - Pseudo eye of the tiger sign in atypical parkinsonism.

PMID- 22610525
TI  - U-statistics in genetic association studies.
AB  - Many common human diseases are complex and are expected to be highly
      heterogeneous, with multiple causative loci and multiple rare and common variants
      at some of the causative loci contributing to the risk of these diseases. Data
      from the genome-wide association studies (GWAS) and metadata such as known gene
      functions and pathways provide the possibility of identifying genetic variants,
      genes and pathways that are associated with complex phenotypes. Single-marker
      based tests have been very successful in identifying thousands of genetic
      variants for hundreds of complex phenotypes. However, these variants only explain
      very small percentages of the heritabilities. To account for the locus- and
      allelic-heterogeneity, gene-based and pathway-based tests can be very useful in
      the next stage of the analysis of GWAS data. U-statistics, which summarize the
      genomic similarity between pair of individuals and link the genomic similarity to
      phenotype similarity, have proved to be very useful for testing the associations
      between a set of single nucleotide polymorphisms and the phenotypes. Compared to
      single marker analysis, the advantages afforded by the U-statistics-based methods
      is large when the number of markers involved is large. We review several
      formulations of U-statistics in genetic association studies and point out the
      links of these statistics with other similarity-based tests of genetic
      association. Finally, potential application of U-statistics in analysis of the
      next-generation sequencing data and rare variants association studies are
      discussed.

PMID- 22610526
TI  - Is the infection rate in primary THA increased after steroid injection?
AB  - BACKGROUND: Injection of the hip is performed for diagnostic and therapeutic
      reasons. Articular cartilage deterioration and increased risk of prosthetic
      infection have been reported with steroid injections. However, the literature
      contains contradictory reports on an increased risk of infection after a
      subsequent THA. QUESTIONS/PURPOSES: We asked whether intraarticular steroid
      injection increased the rate of infection of a subsequent THA. METHODS: We
      retrospectively reviewed records of 175 patients in whom intraarticular steroid
      injections were given under strictly aseptic conditions using a lateral approach
      within 1 year before THA. These patients were matched with others from our
      database who had not received an injection for comorbidities, and for American
      Society of Anesthesiologists score, age, BMI, sex, type of implant, and year of
      THA. RESULTS: We found no differences in the rate of deep or superficial
      infection between the two groups. One patient in the injected group and one in
      the control group had a late chronic infection. In three patients in the injected
      group and one in the control group, one of the intraoperative cultures was
      positive. Five patients in the injected group and seven in the control group had
      superficial infections develop. In seven patients in the injected group and five
      in the control group, there was prolonged wound drainage (> 5 days). None of
      these patients had a deep wound infection at latest followup. CONCLUSIONS: When
      used in strictly aseptic conditions, intraarticular steroid injection of the hip
      did not increase the risk of infection in patients subsequently undergoing THA.
      LEVEL OF EVIDENCE: Level III, therapeutic study. See Instructions for Authors for
      a complete description of levels of evidence.

PMID- 22610527
TI  - Does standing affect acetabular component inclination and version after THA?
AB  - BACKGROUND: Avoiding complications after hip arthroplasty with hard-on-hard
      bearings, especially metal-on-metal, correlates with the position of the
      acetabular component. Supine imaging with conventional radiography has
      traditionally been utilized to assess component inclination (abduction), as well
      as anteversion, after THA and surface replacement arthroplasty (SRA). However,
      most adverse events with hard bearings (excessive wear and squeaking) have
      occurred with loading. Standing imaging, therefore, should provide more
      appropriate measurements. QUESTIONS/PURPOSES: We determined whether standing
      changed standard measurements of acetabular component position using a novel
      biplanar imaging system compared to traditional supine imaging. METHODS: We
      performed simultaneous biplanar standing imaging of the lower extremity with a
      novel imaging system using low radiation collimated beam on 46 patients who
      underwent THA (23) or SRA (23). Patients who had previously undergone THA had
      standard CT scans performed. For patients who underwent SRA, we compared
      acetabular inclination in the supine versus double-limb and single-limb standing.
      RESULTS: Standing anteversion differed from supine anteversion by greater than 5
      degrees  for 12 of 23 patients who underwent THA (range, 5 degrees -16 degrees ).
      For patients who underwent SRA, 13 of 23 patients exhibited a difference of
      greater than 3 degrees  in inclination between supine and double-limb standing
      images, and six of 23 patients exhibited a difference of greater than 3 degrees 
      in inclination between supine and single-limb standing images. CONCLUSIONS:
      Standing changed the acetabular inclination and version in a substantial
      percentage of patients undergoing hip arthroplasty.

PMID- 22610528
TI  - Prereferral MRI use in patients with musculoskeletal tumors is not excessive.
AB  - BACKGROUND: Inappropriate MRI use has been targeted as a particular area of
      concern in orthopaedics, but it is unclear whether and to what extent its use is
      inappropriate in musculoskeletal oncology. QUESTIONS/PURPOSES: We therefore
      evaluated the incidence and cost of inappropriate prereferral MRI among patients
      with musculoskeletal tumors. METHODS: We retrospectively identified 920 patients
      treated in a musculoskeletal oncology clinic between 2009 and 2010. We accepted
      as necessary any MRI for a primary bone sarcoma, for biopsy-proven soft tissue
      sarcomas, for soft tissue masses greater than 5 cm in diameter, for soft tissue
      masses deep to the fascia, for painful soft tissue masses, and for growing soft
      tissue masses. Patients without these criteria were reviewed by a team of
      musculoskeletal oncologists to determine the necessity. The criteria for a repeat
      MRI were failure to show the tumor, lack of gadolinium contrast, lack of T1 or T2
      MRI sequence, or poor image quality. Cost was determined using 2010 Medicare
      reimbursement rates. RESULTS: Of 920 patients, 320 (35%) arrived with a
      prereferral MRI study. Eight of the 320 (3%) studies were unnecessary, and 12
      (4%) were necessary but were repeated. The cost was $11,474, which averages to
      $574 per study and $36 of waste per patient referred with an MRI study.
      CONCLUSIONS: Based on our data, we judged MRI use before referral to our tertiary
      center as not excessive. This is likely attributable, in part, to the relatively
      low use of MRI in our referral base. Inappropriate MRI use in patients with
      tumors may not be as widespread as previously reported. LEVEL OF EVIDENCE: Level
      IV, case series. See Guidelines for Authors for a complete description of levels
      of evidence.

PMID- 22610529
TI  - Sagittal cutting error changes femoral anteroposterior sizing in total knee
      arthroplasty.
AB  - BACKGROUND: Prosthetic alignment and size are important factors in achieving a
      long-term survival in TKA. Although two-dimensional and three-dimensional (3-D)
      planning for component sizing has been introduced, it sometimes is difficult to
      cut the bones accurately according to preoperative planning. It is unclear
      whether changing sagittal alignment of the distal femur affects the AP dimension
      and sizing of the prepared bone. QUESTIONS/PURPOSES: We therefore determined
      whether the AP dimension of the prepared distal femur increases if the distal
      femur is cut in extension and decreases if it is cut in flexion. METHODS: One
      hundred knees were evaluated using 3-D imaging software. The AP dimension of the
      cutting surface was measured when the femoral component was aligned perpendicular
      to the anatomic axis. The measurement was repeated when the distal bone cut was
      planned in flexed positions of 3 degrees  and 5 degrees  and extended positions
      of 3 degrees  and 5 degrees . RESULTS: The AP dimension of the prepared femur was
      increased by 2 and 3 mm with 3 degrees  and 5 degrees  extension, respectively.
      The AP dimension of the prepared femur was decreased by 2 and 3 mm with 3 degrees
      and 5 degrees  flexion, respectively. CONCLUSIONS: Our data suggest upsizing or
      downsizing of the femoral component can occur if the femoral osteotomy is
      performed in at least 3 degrees  extension or flexion. LEVEL OF EVIDENCE: Level
      II, diagnostic study. See Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 22610530
TI  - Nonparametric inference for the cumulative incidence function of a competing
      risk, with an emphasis on confidence bands in the presence of left-truncation.
AB  - Motivated by a study on pregnancy outcome, a computationally simple resampling
      procedure for nonparametric analysis of the cumulative incidence function of a
      competing risk is investigated for left-truncated data. We also modify the
      original procedure to producing the more desirable Greenwood-type variance
      estimates. These approaches are used to construct simultaneous confidence bands
      of the cumulative incidence functions which is otherwise hampered by the
      complicated nature of the covariance process. Simulation results and a real data
      example are provided.

PMID- 22610531
TI  - Diffusion tensor imaging in hydrocephalus--findings before and after shunt
      surgery.
AB  - BACKGROUND: To evaluate changes in diffusion tensor imaging (DTI)-derived
      parameters in patients with hydrocephalus (HC) before and several weeks after
      shunt surgery. METHODS: Thirteen HC patients were examined with DTI before and
      after shunt surgery. In a combined region of interest and whole brain voxel-based
      analysis, different DTI parameters were compared with an age-matched control
      group. RESULTS: Alteration of DTI parameters in HC patients and changes after
      shunt surgery are regionally different. HC patients show an increase in
      fractional anisotropy values based on increases in parallel diffusivity in the
      corticospinal tract. On the other hand, reduced fractional anisotropy values are
      found in the corpus callosum of HC patients. Following shunt surgery, all DTI
      parameters showed a trend towards normalization, yet differences to healthy
      control subjects remained. CONCLUSION: Our results show that DTI parameter
      changes are regionally dependent and need a careful interpretation of the
      underlying diffusivities to serve as a diagnostic or follow-up measure in
      patients with hydrocephalus.

PMID- 22610532
TI  - Alpha-lipoic acid reduces peridural fibrosis after laminectomy of lumbar
      vertebrae in rabbits.
AB  - BACKGROUND: Peridural fibrosis is an inevitable healing process causing failed
      back surgery syndrome after lumbar spinal operations. In this study, alpha-lipoic
      acid (ALA), reported to reduce fibrosis in liver, oral mucosa, and peritoneum,
      investigated as a potential candidate for prevention of peridural fibrosis.
      METHOD: Twelve adult New Zealand white male rabbits were divided into control (n
      = 5) and ALA groups (n = 7). Laminectomy of lumbar spine was performed and ALA
      was applied on the exposed dura mater topically in ALA group. RESULTS: According
      to histological peridural grading, the ALA group (median grade 1) showed
      significantly less peridural fibrosis than the control group (median grade 3, p =
      0.005). CONCLUSIONS: ALA is a promising substance in the prevention of peridural
      fibrosis, especially in early preoperative and postoperative period.

PMID- 22610533
TI  - Tissue elasticity estimated by acoustic radiation force impulse quantification
      depends on the applied transducer force: an experimental study in kidney
      transplant patients.
AB  - OBJECTIVES: Acoustic radiation force impulse (ARFI) quantification estimates
      tissue elasticity by measuring shear-wave velocity (SWV) and has been applied to
      various organs. We evaluated the impact of variations in the transducer force
      applied to the skin on the SWV ultrasound measurements in kidney transplant
      cortex and ARFI's ability to detect fibrosis in kidney transplants. METHODS: SWV
      measurements were performed in the cortex of 31 patients with kidney allografts
      referred for surveillance biopsies. A mechanical device held the transducer and
      applied forces were equal to a compression weight of 22, 275, 490, 975, 2,040 and
      2,990 g. RESULTS: SWV group means were significantly different by repeat measures
      ANOVA [F(2.85,85.91) = 84.75, P < 0.0005 for 22, 275, 490, 975 and 2,040 g
      compression weight] and also by pairwise comparisons. Biopsy specimens were
      sufficient for histological evaluation in 29 of 31 patients. Twelve had grade 0,
      11 grade 1, five grade 2 and one grade 3 fibrosis. One-way ANOVA showed no
      difference in SWV performed with any of the applied transducer forces between
      grafts with various degrees of fibrosis. CONCLUSION: SWV measurements in kidney
      transplants are dependent on the applied transducer force and do not differ in
      grafts with different grades of fibrosis. KEY POINTS: * Acoustic radiation force
      impulses (ARFI) can quantify tissue elasticity during ultrasound examinations. *
      Elasticity estimated by ARFI in kidney transplants depends on applied transducer
      force. * ARFI quantification cannot detect renal allograft fibrosis. * ARFI
      elasticity estimates may in general vary with applied transducer force.

PMID- 22610534
TI  - Ventilation imaging of the paranasal sinuses using xenon-enhanced dynamic single
      energy CT and dual-energy CT: a feasibility study in a nasal cast.
AB  - OBJECTIVE: To show the feasibility of dual-energy CT (DECT) and dynamic CT for
      ventilation imaging of the paranasal sinuses in a nasal cast. METHODS: In a first
      trial, xenon gas was administered to a nasal cast with a laminar flow of 7 L/min.
      Dynamic CT acquisitions of the nasal cavity and the sinuses were performed. This
      procedure was repeated with pulsating xenon flow. Local xenon concentrations in
      the different compartments of the model were determined on the basis of the
      enhancement levels. In a second trial, DECT measurements were performed both
      during laminar and pulsating xenon administration and the xenon concentrations
      were quantified directly. RESULTS: Neither with dynamic CT nor DECT could xenon
      related enhancement be detected in the sinuses during laminar airflow. Using
      pulsating flow, dynamic imaging showed a xenon wash-in and wash-out in the
      sinuses that followed a mono-exponential function with time constants of a few
      seconds. Accordingly, DECT revealed xenon enhancement in the sinuses only after
      pulsating xenon administration. CONCLUSION: The feasibility of xenon-enhanced
      DECT for ventilation imaging was proven in a nasal cast. The superiority of
      pulsating gas flow for the administration of gas or aerosolised drugs to the
      paranasal sinuses was demonstrated. KEY POINTS : * Ventilation of the paranasal
      sinuses is poorly understood. * Dual-energy CT ventilation imaging has been
      explored using phantom simulation. * Xenon can be seen in the paranasal sinuses
      using pulsating xenon flow. * Dual-energy CT uses a lower radiation dose compared
      with dynamic ventilation CT.

PMID- 22610535
TI  - The oxysterol receptors LXRalpha and LXRbeta suppress proliferation in the colon.
AB  - The oxysterol receptors LXRalpha and LXRbeta are members of the nuclear receptor
      family and established transcriptional regulators of lipid metabolism with
      additional anti-inflammatory functions. Recent investigations have indicated an
      important role of LXRs in the control of proliferation. Here we further extend
      this knowledge to human colon cancer cells and proliferation in mouse colon. We
      show that activation of LXRs leads to a robust cell cycle arrest in colorectal
      adenocarcinoma cell lines. At the molecular level LXRs control expression of
      several cell cycle genes including Skp2, c-Myc, CDKs, cyclins, and p15.
      Furthermore, activation of LXRs causes hypo-phosphorylation of the retinoblastoma
      (Rb) tumor suppressor protein. Experiments performed in vivo show that the colon
      structure appears to be intact in LXR null mice. However, LXRalphabeta(-/-) mice
      show a significant increase of proliferation markers in colon compared to wild
      type mice and administration of the LXR specific agonist, GW3965 significantly
      reduced expression of proliferation in mouse colon. Taken together, these
      findings point toward a strong anti-proliferative effect of LXRs in colon
      revealing the potential of LXR ligands as possible anti cancer agents.

PMID- 22610536
TI  - Opportunities and challenges for smallholder pig production systems in a
      mountainous region of Xishuangbanna, Yunnan Province, China.
AB  - China's small-scale pig keepers are the largest community of pork producers
      worldwide. About 56 % of the world's pigs originate from such systems, each
      producing 2-5 head per year. This study analyzes pig smallholders in
      Xishuangbanna, a prefecture of Yunnan Province. Categorical principal component
      analysis and two-step cluster analysis were used to identify three main
      production systems: livestock-corn-based (LB; 41 %), rubber based (RB; 39 %), and
      pig based (PB; 20 %) systems. RB farms earn high income from rubber and fatten
      cross-bred pigs, often using purchased feeds. PB farms own similar-sized rubber
      plantations and raise pigs, with fodder mainly being cultivated and collected in
      the forest. LB farms grow corn, rice, and tea while also raising pigs, fed with
      collected and cultivated fodder as well. About one third of pigs were marketed
      (LB, 20 %; RB, 42 %; PB, 25 %), and local pig meat is highly appreciated in the
      nearby town. High mortality, low reproductive performance, and widespread
      malnourishment are the systems' main constraints. Basic training in hygiene and
      reproduction management could significantly increase production; most effective
      measures would be counterbalancing seasonal malnourishment and exploration of
      locally available protein feeds. Through support by external expertise, farmers
      could more effectively trade their pigs at lucrative town markets.

PMID- 22610537
TI  - Influence of socioeconomic factors on production constraints faced by indigenous
      chicken producers in South Africa.
AB  - Individual interviews were conducted in 137 households using semi-structured
      questionnaires to determine the influence of socioeconomic factors on production
      constraints faced by indigenous chicken producers in the rural areas of South
      Africa. The major constraints to village chicken production were mortality (95 %
      of the households) followed by feed shortage (85 %) and low chicken sales (72 %).
      The logistic regression model showed that households that owned
      imported/crossbred chickens practiced extensive production system without housing
      structures and did not have vaccines were more likely to experience high levels
      of chicken mortality. Poor and youth-headed households with no supplements and
      vaccines had high probability of Newcastle disease. The probability of a
      household to experience chicken feed shortage was lower in households that owned
      indigenous chickens than those that owned imported/crossbred chickens (odds
      ratio, 11.68; 95 % confidence interval, 1.19-27.44). Youth-headed households that
      had small flocks and no access to veterinary services were not likely to sell
      chickens. It was concluded that gender, age, wealth status, production system,
      chicken flock size, type of chicken breed owned, accessibility of veterinary
      services, availability of supplements, vaccines and shelter influence village
      chicken farmer's production constraints such as feed availability, chicken
      mortality, prevalence of diseases and chicken sales.

PMID- 22610538
TI  - Molecular and serological characterization of Leptospira interrogans serovar
      Canicola isolated from dogs, swine, and bovine in Brazil.
AB  - The identification of Leptospira clinical isolates through genotyping and
      serotyping, besides the recognition of its reservoirs, are important tools for
      understanding the epidemiology of leptospirosis, and they are also keys for
      identifying new species and serovars. Fourteen clinical isolates from animals
      were characterized by means of single enzyme amplified length polymorphism,
      variable number of tandem repeat analysis, pulsed field gel electrophoresis, and
      serotyping. All isolates were identified as Leptospira interrogans, serovar
      Canicola. Infections by this serovar occur in urban regions, where dogs represent
      the main maintenance hosts, whereas bovine and swine may act as reservoirs of
      serovar Canicola in rural areas. Both urban and rural aspects of leptospirosis,
      and the role of domestic animals as maintenance hosts, cannot be neglected in
      developing and developed countries.

PMID- 22610539
TI  - Size-tunable polymeric nanoreactors for one-pot synthesis and encapsulation of
      quantum dots.
AB  - Hydrophilic polymeric nanoparticles are synthesized through a Bergman cyclization
      mediated intramolecular chain collapse of structurally well-defined linear
      polymers, and then used as size-tunable nanoreactors to fabricate and encapsulate
      quantum dots in a one-pot reaction. Crystalline quantum dots are formed in all of
      these nanoreactors and visualized by transmission electron microscopy. Smaller
      nanoreactors produce one quantum dot each while larger nanoreactors form a
      number, resulting in fluorescence quenching. By controlling the molecular weight
      of the linear polymer precursor, a variable number of nanocrystals are fabricated
      and assembled in a single nanoreactor.

PMID- 22610540
TI  - Primary skeletal muscle anaplastic large cell lymphoma, positive for anaplastic
      lymphoma kinase, exhibiting multiple skeletal muscle lesions.

PMID- 22610541
TI  - Acceptance as a process variable in relation to catastrophizing in
      multidisciplinary pain treatment.
AB  - BACKGROUND: The underlying processes of change that contribute to the
      effectiveness of multidisciplinary pain treatment require clarification. Previous
      research has found support for pain acceptance as a process variable in
      acceptance-based treatment. Preliminary findings indicate that pain acceptance
      may also be a process variable in traditional cognitive behavioural therapy
      (CBT). The aim of this study was to investigate the role of pain acceptance as a
      process variable in CBT relative to two empirically supported process variables,
      namely catastrophizing and pain intensity. METHODS: Patients with chronic pain (n
      = 186) attended a 3-week, multidisciplinary pain programme, which was CBT based.
      Patients completed a measure of pain intensity; the Chronic Pain Acceptance
      Questionnaire; the catastrophizing subscale of the Pain Response Self-Statements
      Scale; the Roland Morris Disability Questionnaire; the Depression Anxiety and
      Stress Scale; and two measures of physical functioning at pretreatment, post
      treatment and 3-month follow-up. RESULTS: Both acceptance and catastrophizing
      showed statistically significant and clinically relevant changes from pre- to
      post-treatment. Changes in both acceptance and catastrophizing showed a
      significant correlation with changes in almost all of the outcome variables.
      Regression analyses demonstrated that change in acceptance was a significant
      predictor of changes in depression, disability, timed walk and sit-to-stand
      performance, after controlling for changes in catastrophizing and pain intensity.
      CONCLUSIONS: Although not specifically targeted in CBT treatment, acceptance of
      pain was an important process variable that contributed to CBT treatment outcomes
      after controlling for changes in pain intensity and catastrophizing. Implications
      for future research and clinical practice are discussed.

PMID- 22610543
TI  - Neutrophil dysfunction induced by hyperglycemia: modulation of myeloperoxidase
      activity.
AB  - Our data suggest that impaired activity of myeloperoxidase (MPO) may play an
      important role in the dysfunction of neutrophils from hyperglycemic rats.
      Neutrophil biochemical pathways include the NADPH oxidase system and the MPO
      enzyme. They both play important role in the killing function of neutrophils. The
      effect of hyperglycemia on the activity of these enzymes and the consequences
      with regard to Candida albicans phagocytosis and the microbicidal property of rat
      peritoneal neutrophils is evaluated here. The NADPH oxidase system activity was
      measured using chemiluminescence and cytochrome C reduction assays. MPO activity
      was measured by monitoring HOCl production, and MPO protein expression was
      analysed using Western blot and immunofluorescence. C. albicans phagocytosis and
      death were evaluated by optical microscopy using the May-Grunwald-Giemsa staining
      method. ROS generation kinetic was slightly delayed in the diabetic group. MPO
      expression levels were higher in diabetic neutrophils; however, MPO activity was
      decreased in these same neutrophils compared with the controls. C. albicans
      phagocytosis and killing were lower in the diabetic neutrophils. Based on our
      experimental model, the phagocytic and killing functions of neutrophil
      phagocytosis are impaired in diabetic rats because of the decreased production of
      HOCl, highlighting the importance of MPO in the microbicidal function of
      neutrophils.

PMID- 22610542
TI  - NMR line shapes and multi-state binding equilibria.
AB  - Biological function of proteins relies on conformational transitions and binding
      of specific ligands. Protein-ligand interactions are thermodynamically and
      kinetically coupled to conformational changes in protein structures as
      conceptualized by the models of pre-existing equilibria and induced fit. NMR
      spectroscopy is particularly sensitive to complex ligand-binding modes-NMR line
      shape analysis can provide for thermodynamic and kinetic constants of ligand
      binding equilibria with the site-specific resolution. However, broad use of line
      shape analysis is hampered by complexity of NMR line shapes in multi-state
      systems. To facilitate interpretation of such spectral patterns, I
      computationally explored systems where isomerization or dimerization of a protein
      (receptor) molecule is coupled to binding of a ligand. Through an extensive
      analysis of multiple exchange regimes for a family of three-state models, I
      identified signature features to guide an NMR experimentalist in recognizing
      specific interaction mechanisms. Results show that distinct multi-state models
      may produce very similar spectral patterns. I also discussed aggregation of a
      receptor as a possible source of spurious three-state line shapes and provided
      specific suggestions for complementary experiments that can ensure reliable
      mechanistic insight.

PMID- 22610544
TI  - Visualization of the interactome: what are we looking at?
AB  - Network visualization of the interactome has been become routine in systems
      biology research. Not only does it serve as an illustration on the cellular
      organization of protein-protein interactions, it also serves as a biological
      context for gaining insights from high-throughput data. However, the challenges
      to produce an effective visualization have been great owing to the fact that the
      scale, biological context and dynamics of any given interactome are too large and
      complex to be captured by a single visualization. Visualization design therefore
      requires a pragmatic trade-off between capturing biological concept and being
      comprehensible. In this review, we focus on the biological interpretation of
      different network visualizations. We will draw on examples predominantly from our
      experiences but elaborate them in the context of the broader field. A rich
      variety of networks will be introduced including interactomes and the complexome
      in 2D, interactomes in 2.5D and 3D and dynamic networks.

PMID- 22610545
TI  - Structural biology of plant sulfur metabolism: from assimilation to biosynthesis.
AB  - Sulfur is an essential element that must be assimilated by all organisms;
      however, the metabolic pathways for this task vary significantly, even among
      individual genera of bacteria, and especially so among eukaryotes. While all
      organisms require sulfurous amino acids, plants require specialized sulfur
      containing metabolites, such as glucosinolates and allylsulfur compounds, for
      protection from herbivory and microbial infection; and the synthesis of
      specialized peptides (i.e., glutathione and phytochelatins) for protection
      against reactive oxygen species and exposure to transition metals, such as
      cadmium. In order to provide the complex array of sulfur-containing metabolites
      essential to plant viability, flux through the sulfur assimilatory pathway must
      be tightly regulated by controlling enzymatic activity. The X-ray crystal
      structures of several primary sulfur assimilatory enzymes, complemented by
      kinetics, have revealed mechanisms of enzymatic regulation (i.e., via redox state
      and protein-protein interaction) in these biosynthetic pathways, in addition to
      the chemical mechanisms of catalysis. This review summarizes the state of our
      structural knowledge of primary and secondary sulfur assimilatory enzymes from
      plants.

PMID- 22610546
TI  - Gill-arch musculature of the quillback Carpiodes cyprinus (Cypriniformes:
      Catostomidae) with a comparison to cyprinids.
AB  - Although the gill-arch osteology of Cypriniformes has been well studied,
      comparable works on gill-arch musculature are scarce. The focus of previous
      studies has been on Cyprinidae while other families have received little or no
      attention. Consequently, generalizations for Cypriniformes have been made from
      the musculature of cyprinid gill-arches. This study describes the gill-arch
      musculature of a catostomid, the quillback Carpiodes cyprinus, and demonstrates
      that there are striking differences in the overall gill-arch musculature of
      catostomids in comparison to cyprinids, especially in the dorsal gill-arch
      region. Of the 23 muscles found in the dorsal gill-arch region of cyprinids, only
      13 were present in C. cyprinus. Muscles that are absent include adductores 1-5,
      levator internus 4, levator ceratobranchialis 5 accessorius, retractor
      ceratobranchialis 5 externus, retractor ceratobranchialis 5 internus, and the
      retractor ceratobranchialis 5 transversus. In the ventral gill-arch region, the
      rectus communis is absent. The derived scrolling shape of the dorsal gill-arch
      skeleton associated with food processing is likely related to the change in
      musculature.

PMID- 22610547
TI  - Structural elucidation of the tetrasaccharide pool in enoxaparin sodium.
AB  - Low-molecular-weight heparins (LMWHs) are produced from heparin by various
      depolymerization strategies, which result in a reduction of the average molecular
      weight of the polysaccharide chains, a reduction of the anti-factor IIa activity
      (and a concomitant increase in the anti-factor Xa/anti-factor IIa ratio), and
      introduction of process-related structural signatures. Numerous techniques have
      been developed to characterize LMWHs and to measure the type and extent of
      structural modifications that are introduced as a function of the
      depolymerization process. We present here an analysis of the tetrasaccharide pool
      of enoxaparin sodium, a LMWH produced by chemical beta-elimination of heparin
      benzyl ester. We identify the predominant sequences present within the
      tetrasaccharide pool and demonstrate that this pool provides a sensitive,
      specific readout of the physicochemical process conditions used to generate
      enoxaparin sodium.

PMID- 22610548
TI  - Advancing formaldehyde cross-linking towards quantitative proteomic applications.
AB  - Formaldehyde is a key fixation reagent. This review explores its application in
      combination with qualitative and quantitative mass spectrometry (MS). Formalin
      fixed and paraffin-embedded (FFPE) tissues form a large reservoir of biologically
      valuable samples and their investigation by MS has only recently started.
      Furthermore, formaldehyde can be used to stabilise protein-protein interactions
      in living cells. Because formaldehyde is able to modify proteins, performing MS
      analysis on these samples can pose a challenge. Here we discuss the chemistry of
      formaldehyde cross-linking, describe the problems of and progress in these two
      applications and their common aspects, and evaluate the potential of these
      methods for the future.

PMID- 22610549
TI  - HPLC method for rapidly following biodiesel fuel transesterification reaction
      progress using a core-shell column.
AB  - There are a wide and growing variety of feedstocks for biodiesel fuel. Most
      commonly, these feedstocks contain triglycerides which are transesterified into
      the fatty acid alkyl esters (FAAEs) which comprise biodiesel fuel. While the
      tranesterification reaction itself is simple, monitoring the reaction progress
      and reaction products is not. Gas chromatography-mass spectrometry is useful for
      assessing the FAAE products, but does not directly address either the tri-, di-,
      or monoglycerides present from incomplete transesterification or the free fatty
      acids which may also be present. Analysis of the biodiesel reaction mixture is
      complicated by the solubility and physical property differences among the
      components of the tranesterification reaction mixture. In this contribution, we
      present a simple, rapid HPLC method which allows for monitoring all of the main
      components in a biodiesel fuel transesterification reaction, with specific
      emphasis on the ability to monitor the reaction as a function of time. The
      utilization of a relatively new, core-shell stationary phase for the HPLC column
      allows for efficient separation of peaks with short elution times, saving both
      time and solvent.

PMID- 22610550
TI  - Current thoughts on the therapeutic potential of stem cell.
AB  - Stem cells are considered as potential therapy for inflammatory disorders, tissue
      repair, and gene delivery, among others. The heterogeneity of a disease and the
      underlying disorder of a patient bring up the question on the method by which
      stem cells should be delivered. This summary discusses potential complex
      interactions among mediators at sites to tissue insults with stem cells. The
      chapter selects mesenchymal stem cells (MSCs) as a model, although the discussion
      is relevant to all stem cells. The review examines how MSCs and their
      differentiated cells can develop cross communication with soluble factors and
      cells within the region of tissue damage. Inflammatory cytokines, IL-1, TNFalpha,
      and TGFbeta are selected to explain how they can affect the responses of MSCs,
      while predisposing the stem cells to oncogenic event. By understanding the varied
      functions of MSCs, one will be able to intervene to form a balance in functions,
      ultimately to achieve safety and efficient application. Cytokines can affect the
      expression of pluripotent genes such as REST and Oct-4. REST is a critical gene
      in the decision of a cell to express or repress neural genes. Since cytokines can
      affect microRNAs, the review incorporates this family of molecules as mediators
      of cytokine effects. IFNgamma, although an inflammatory mediator, is central to
      the expression of MHC-II on MSCs. Therefore, it is included to discuss its role
      in the transplantation of stem cells across allogeneic barrier. In summary, this
      chapter discusses several potential areas that need to be addressed for safe and
      efficient delivery of stem cells, and argue for the incorporation of
      microenvironmental factors in the studies.

PMID- 22610551
TI  - A unique FACS method to isolate stem cells in planarian.
AB  - Fluorescence-activated cell sorting (FACS) is a useful method for stem cell
      biology, which enables us to isolate the living stem cells of interest from
      mixture of a variety of cells. In general, the target cells for FACS need to be
      labeled for various cell surface markers. However, in non-model organisms, we
      usually do not have specific labels for such cell surface markers. Here, we
      describe a method for isolating stem cells from non-model organisms, such as
      planarians, based on physiological and morphological properties of the stem
      cells. This method may also be applicable to other non-model animals.

PMID- 22610552
TI  - Identification of neural stem cells in the Drosophila larval brain.
AB  - The balance between self-renewal and differentiation must be tightly regulated in
      somatic stem cells to ensure proper tissue generation and to prevent tumorlike
      overgrowth. A Drosophila larval brain lobe consists of the central brain and the
      optic lobe and possesses three well-defined neural stem cell lineages that
      generate differentiated cells in a highly reproducible pattern. Unambiguous
      identification of various cell types in these stem cell lineages is pivotal for
      studying the regulation of neural stem cells and progenitor cells at a single
      cell resolution. This chapter will describe the methodology for collection and
      processing of larval brains for examination by fluorescence confocal microscopy.

PMID- 22610553
TI  - Generation and staining of intestinal stem cell lineage in adult midgut.
AB  - Stem cell-mediated tissue repair is a promising approach in regenerative
      medicine. Intestinal epithelium is the most rapidly self-renewing tissue in adult
      mammals. Recently, using lineage tracing and molecular marker labeling,
      intestinal stem cells (ISCs) have been identified in Drosophila adult midgut.
      ISCs reside at the basement membrane and are multipotent as they produce both
      enterocytes and enteroendocrine cells. The adult Drosophila midgut provides an
      excellent in vivo model organ to study ISC behavior during aging, stress,
      regeneration, and infection. It has been demonstrated that Notch, Janus
      kinase/signal transducer and activator of transcription, epidermal growth factor
      receptor/mitogen-activated protein kinase, Hippo, and wingless signaling pathways
      regulate ISCs proliferation and differentiation. There are plenty of genetic
      tools and markers developed in recent years in Drosophila stem cell studies.
      These tools and markers are essential in the precise identification of stem cells
      as well as manipulation of genes in stem cell regulation. Here, we describe the
      details of genetic tools, markers, and immunolabeling techniques used in
      identification and characterization of adult midgut stem cells in Drosophila.

PMID- 22610554
TI  - Developing a quantitative in vivo tissue reconstitution assay to assess the
      relative potency of candidate populations of mouse oesophageal epithelial cells.
AB  - Proliferation in mouse oesophageal epithelial cells is confined to the basal
      layer of the epithelium. Within this population, it is possible to discriminate
      different sub-populations using a combination of cell kinetic studies and
      functional assays. In particular, it is possible to distinguish basal epithelial
      cells, which are post-mitotic and destined to leave the basal layer and
      differentiate compared with those cells that remain in the cycling pool. Within
      the cycling basal population, there appears to be a hierarchy with respect to the
      rate of cell turnover which may reflect a hierarchy of "stemness", although it
      has not been possible to demonstrate functional differences between these
      populations using current in vivo tissue reconstitution assays. The aim of this
      chapter is to describe the development of a quantitative in vivo tissue
      reconstitution assay to assess the potency of candidate stem cell populations
      within the mouse oesophageal epithelium.

PMID- 22610555
TI  - Identification, isolation, and culture of intestinal epithelial stem cells from
      murine intestine.
AB  - The study of adult stem cell populations provides insight into the mechanisms
      that regulate tissue maintenance in normal physiology and many disease states.
      With an impressive rate of epithelial renewal driven by a pool of multipotent
      stem cells, the intestine is a particularly advantageous model system for the
      study of adult stem cells. Until recently, the isolation and in vitro study of
      intestinal epithelial stem cells (IESCs) was not possible due to the lack of
      biomarkers and culture techniques. However, advances in molecular
      characterization and culture of IESCs have made in vitro studies on this cell
      type amenable to most laboratories. The methods described in this chapter will
      allow the investigator to adapt newly established techniques toward downstream
      analysis of IESCs in vitro.

PMID- 22610556
TI  - Isolation and characterization of distal lung progenitor cells.
AB  - The majority of epithelial cells in the distal lung of rodents and humans are
      quiescent in vivo, yet certain cell populations retain an intrinsic capacity to
      proliferate and differentiate in response to lung injury or in appropriate
      culture settings, thus giving them properties of stem/progenitor cells. Here, we
      describe the isolation of two such populations from adult mouse lung: alveolar
      epithelial type 2 cells (AEC2), which can generate alveolar epithelial type 1
      cells, and bronchioalveolar stem cells (BASCs), which in culture can reproduce
      themselves, as well as generate a small number of other distal lung epithelial
      cell types. These primary epithelial cells are typically isolated using enzyme
      digestion, mechanical disruption, and serial filtration. AEC2 and BASCs are
      distinguished from other distal lung cells by expression of specific markers as
      detected by fluorescence-activated cell sorting, immunohistochemistry, or a
      combination of both of these techniques.

PMID- 22610557
TI  - Transplantation of mouse fetal liver cells for analyzing the function of
      hematopoietic stem and progenitor cells.
AB  - Hematopoietic stem cells are defined by their ability to self-renew and
      differentiate through progenitor cell stages into all types of mature blood
      cells. Gene-targeting studies in mice have demonstrated that many genes are
      essential for the generation and function of hematopoietic stem and progenitor
      cells. For definitively analyzing the function of these cells, transplantation
      studies have to be performed. In this chapter, we describe methods to isolate and
      transplant fetal liver cells as well as how to analyze donor cell reconstitution.
      This protocol is tailored toward mouse models where embryonic lethality precludes
      analysis of adult hematopoiesis or where it is suspected that the function of
      fetal liver hematopoietic stem and progenitor cells is compromised.

PMID- 22610558
TI  - Convenient and efficient enrichment of the CD133+ liver cells from rat fetal
      liver as a source of liver stem/progenitor cells.
AB  - Although stem cells are commonly isolated by fluorescence-activated cell sorting
      or magnetic affinity cell sorting, they are very expensive, and they need known
      markers. However, there is no specific marker for liver stem/progenitor cells
      (LSPCs). Here, we describe a convenient and efficient method (three-step method)
      to enrich LSPCs. The fetal liver cells (FLCs) were firstly enriched by Percoll
      discontinuous gradient centrifugation from the rat fetal liver. Then the FLCs in
      culture were purified to be homogeneous in size by differential trypsinization
      and differential adherence. Finally, fetal liver stem/progenitor cells (FLSPCs)
      were enriched from purified FLCs by Percoll continuous gradient centrifugation.
      Flow cytometric analysis combining with marker CD133 was used to detect the
      purity of FLSPCs and evaluate the isolating effects of the three-step method.

PMID- 22610559
TI  - Assessing the potential clinical utility of transplantations of neural and
      mesenchymal stem cells for treating neurodegenerative diseases.
AB  - Treatments for neurodegenerative diseases have little impact on the long-term
      patient health. However, cellular transplants of neuroblasts derived from the
      aborted embryonic brain tissue in animal models of neurodegenerative disorders
      and in patients have demonstrated survival and functionality in the brain.
      However, ethical and functional problems due to the use of this fetal tissue
      stopped most of the clinical trials. Therefore, new cell sources were needed, and
      scientists focused on neural (NSCs) and mesenchymal stem cells (MSCs). When
      transplanted in the brain of animals with Parkinson's or Huntington's disease,
      NSCs and MSCs were able to induce partial functional recovery by promoting
      neuroprotection and immunomodulation. MSCs are more readily accessible than NSCs
      due to sources such as the bone marrow. However, MSCs are not capable of
      differentiating into neurons in vivo where NSCs are. Thus, transplantation of
      NSCs and MSCs is interesting for brain regenerative medicine. In this chapter, we
      detail the methods for NSCs and MSCs isolation as well as the transplantation
      procedures used to treat rodent models of neurodegenerative damage.

PMID- 22610560
TI  - Functional identification of neural stem cell-derived oligodendrocytes.
AB  - Directing neural stem cells (NSCs) differentiation towards oligodendroglial cell
      lineage is a crucial step in the endeavor of developing cell replacement-based
      therapies for demyelinating diseases. Evaluation of NSCs differentiation is
      mostly performed by methodologies that use fixed cells, like immunocytochemistry,
      or lysates, like Western blot. On the other hand, electrophysiology allows
      differentiation studies on living cells, but it is highly time-consuming and
      endowed with important limitations concerning population studies. Herein, we
      describe a functional method, based on single cell calcium imaging, which
      accurately and rapidly distinguishes cell types among NSCs progeny, in living
      cultures prepared from the major reservoir of NSCs in the postnatal mouse brain,
      the subventricular zone (SVZ). Indeed, by applying a rational sequence of three
      stimuli-KCl, histamine, and thrombin-to the heterogeneous SVZ cell population,
      one can identify each cell phenotype according to its unique calcium signature.
      Mature oligodendrocytes, the myelin-forming cells of the central nervous system,
      are the thrombin-responsive cells in SVZ cell culture and display no
      intracellular calcium increase upon KCl or histamine perfusion. On the other
      hand, KCl and histamine stimulate neurons and immature cells, respectively. The
      method described in this chapter is a valuable tool to identify novel pro
      oligodendrogenic compounds, which may play an important role in the design of
      future treatments for demyelinating disorders such as multiple sclerosis.

PMID- 22610562
TI  - A reporter assay to detect transfer and targeting of miRNAs in stem cell-breast
      cancer co-cultures.
AB  - MicroRNAs (miRNAs) are a class of small molecules, which regulate cellular
      function by mediating transient translational repression. Recent studies have
      demonstrated a role for miRNAs as important modulators of stem cell function that
      can be transferred from cell to cell through gap junctional intercellular
      communication. Similar transfer of miRNAs has been implicated in the etiology of
      breast cancer dormancy. To this end, we have developed a miRNA reporter assay to
      assess the ability of miRNAs to be transferred between stem and breast cancer
      cells and target a specific recognition sequence.

PMID- 22610561
TI  - Stem/progenitor cells in murine mammary gland: isolation and functional
      characterization.
AB  - The presence of adult functional mammary epithelial stem/progenitor cells in
      mammary gland and recent identification of enriched fraction of transplantable
      mammary stem cells (MaSCs) through specific cell surface markers have
      revolutionized the study to delineate the role of mammary stem/progenitor
      functions in both mammary gland development and mammary tumorigenesis. In this
      chapter, we have described detailed methods of isolation of mammary epithelial
      cells from murine mammary glands, enrichment of stem/progenitor fractions by
      fluorescence-activated cell sorting (FACS), in vitro mammosphere culture, and
      differentiation assays in two- and three-dimensional culture. We have also
      described the detailed protocol of in vivo cleared mammary fat pad
      transplantation assay for the assessment of the MaSC repopulating activity, which
      indicates their multilineage differentiation and self-renewal potential in vivo
      and is considered the "gold standard" assay of functional stem cells.

PMID- 22610563
TI  - Isolation, culture, and osteogenic/chondrogenic differentiation of bone marrow
      derived mesenchymal stem cells.
AB  - Musculoskeletal disorders, as non-healing fractures and large bone defects,
      articular cartilage and subchondral bone injuries, often result in lifelong
      chronic pain and compromised quality of life. Although generally a natural
      process, failure of large bone defects to heal such as after complex fractures,
      resection of tumours, infections, or revisions of joint replacements remains a
      critical challenge that requires more appropriate solutions as those currently
      available. In addition, regeneration of chondral and osteochondral defects
      continues to be a challenge until to date. A profound understanding of the
      underlying mechanisms of endogenous regeneration is a prerequisite for successful
      bone and cartilage regeneration. Presently, one of the most promising therapeutic
      approaches is cell-based tissue engineering which provides a healthy population
      of cells to the injured site. Use of differentiated cells has severe limitations;
      an excellent alternative would be the application of adult marrow stromal
      cells/mesenchymal stem cells (MSC) which possess extensive proliferation
      potential and proven capability to differentiate along the osteochondral pathway.
      The process of osteo-/chondrogenesis can be mimicked in vitro by inducing osteo
      chondroprogenitor stem cells to undergo osteogenesis and chondrogenesis through
      exposure of osteo-/chondrogenic favourable microenvironmental, mechanical, and
      nutritional conditions. This chapter provides comprehensive protocols for the
      isolation, expansion, and osteo-/chondrogenic differentiation of adult bone
      marrow-derived MSC.

PMID- 22610564
TI  - Obtaining freshly isolated and cultured mesenchymal stem cells from human adipose
      tissue.
AB  - The stromal compartment of adipose tissue harbors mesenchymal stem cells (MSCs)
      (also called stromal stem cells) that display extensive proliferative capacity
      and multilineage differentiation potential. Such cells offer a practical avenue
      of generating patient-matched tissue for use in regenerative medicine. It is
      relatively easy to isolate these cells from adipose tissue in large enough
      quantities (tens of millions) to allow for their clinical use in a native,
      uncultured form. Alternatively, MSCs from adipose tissue can be expanded and
      differentiated into the desired tissue type in vitro using straightforward cell
      culture techniques. In this chapter, we outline procedures for isolating large
      numbers of highly purified MSCs from human adipose tissue in their native,
      uncultured form and methods for their subsequent expansion and differentiation in
      vitro.

PMID- 22610565
TI  - Collection, processing, and banking of umbilical cord blood stem cells for
      transplantation and regenerative medicine.
AB  - Collection and banking of umbilical cord blood can provide a virtually unlimited
      source of ethnically diverse stem cell donors. It can be used in place of bone
      marrow or peripheral blood stem cells for hematologic transplants as well as in a
      variety of regenerative medicine applications. In this study, we review the
      latest developments in cord blood banking. We have banked over 300,000
      collections at our facility, which were processed by either Ficoll or AXP
      methodologies. An average 95-99% processing efficiency was obtained. Processed
      samples can be frozen in either cryovials or bags and banked in the vapor phase
      of a liquid nitrogen dewar for prolonged periods of time. In conclusion, it is
      possible to simply and reproducibly harvest, process, and bank cord blood samples
      using currently available technology.

PMID- 22610566
TI  - Generation of functional islets from human umbilical cord and placenta derived
      mesenchymal stem cells.
AB  - Bone marrow-derived mesenchymal stem cells (BM-MSCs) have been used for
      allogeneic application in tissue engineering but have certain drawbacks.
      Therefore, mesenchymal stem cells (MSCs) derived from other adult tissue sources
      have been considered as an alternative. The human umbilical cord and placenta are
      easily available noncontroversial sources of human tissue, which are often
      discarded as biological waste, and their collection is noninvasive. These sources
      of MSCs are not subjected to ethical constraints, as in the case of embryonic
      stem cells. MSCs derived from umbilical cord and placenta are multipotent and
      have the ability to differentiate into various cell types crossing the lineage
      boundary towards endodermal lineage. The aim of this chapter is to provide a
      detailed reproducible cookbook protocol for the isolation, propagation,
      characterization, and differentiation of MSCs derived from human umbilical cord
      and placenta with special reference to harnessing their potential towards
      pancreatic/islet lineage for utilization as a cell therapy product. We show here
      that mesenchymal stromal cells can be extensively expanded from umbilical cord
      and placenta of human origin retaining their multilineage differentiation
      potential in vitro. Our report indicates that postnatal tissues obtained as
      delivery waste represent a rich source of mesenchymal stromal cells, which can be
      differentiated into functional islets employing three-stage protocol developed by
      our group. These islets could be used as novel in vitro model for screening
      hypoglycemics/insulin secretagogues, thus reducing animal experimentation for
      this purpose and for the future human islet transplantation programs to treat
      diabetes.

PMID- 22610567
TI  - Isolation and characterization of human prostate stem/progenitor cells.
AB  - Isolation of prostate epithelial cells with stem/progenitor characteristics may
      enable further evaluation of the hierarchy of prostate glandular development and
      malignant transformation. Prostate epithelial cells capable of sphere formation
      in semisolid cultures possess stem/progenitor cell characteristics. This is
      demonstrated by self-renewal (via indefinite passaging) and in vivo
      differentiation into prostate tubules with discreet basal and luminal layers.
      Here, we describe a method for isolating prostate stem/progenitor cells from
      human tissues via in vitro prostasphere formation. Prostate tissue regeneration
      using human prostaspheres is also described, enabling the differentiation
      potential of sphere-forming cells to be observed.

PMID- 22610568
TI  - Isolation and expansion of adult cardiac stem/progenitor cells in the form of
      cardiospheres from human cardiac biopsies and murine hearts.
AB  - The successful isolation and ex vivo expansion of resident cardiac
      stem/progenitor cells from human heart biopsies has allowed us to study their
      biological characteristics and their applications in therapeutic approaches for
      the repair of ischemic/infarcted heart, the preparation of tissue-engineered
      cardiac grafts and, possibly, the design of cellular kits for drug screening
      applications. From the first publication of the original method in 2004, several
      adjustments and slight changes have been introduced to optimize and adjust the
      procedure to the evolving experimental and translational needs. Moreover, due to
      the wide applicability of such a method (which is based on the exploitation of
      intrinsic functional properties of cells with regenerative properties that are
      present in most tissues), the key steps of this procedure have been used to
      derive several kinds of tissue-specific adult stem cells for preclinical or
      clinical purposes.In order to define the original procedure, complete with the up
      to-date modifications introduced through the years, an exhaustive description of
      the current protocol is performed in this chapter, with particular attention in
      highlighting critical steps and troubleshoots. The procedure described here
      consists of modular steps, that could be employed to derive cells from any kind
      of tissue biopsy, and needs to be considered the gold standard of all the so
      called "explant methods" or "cardiosphere methods," and it represents a milestone
      in the clinical translation of autologous cell therapy.

PMID- 22610569
TI  - Isolation and differentiation of human cardiomyocyte progenitor cells into
      cardiomyocytes.
AB  - To date, there is no suitable in vitro model to study human adult cardiac cell
      biology. Here, we describe a method for efficient isolation and expansion of
      human cardiomyocyte progenitor cells (CMPCs) from cardiac surgical waste or,
      alternatively, from fetal heart tissue. Additionally, we provide a detailed in
      vitro protocol for efficient differentiation of CMPCs into cardiomyocytes with
      great efficiency (80-90% of differentiation). Once CMPCs are rapidly dividing
      (approximately 1 month after isolation), differentiation can be achieved in 3-4
      weeks.

PMID- 22610570
TI  - Isolation, expansion, and characterization of human islet-derived progenitor
      cells.
AB  - Islet transplantation is a widely accepted and practiced cell replacement therapy
      for treatment of diabetes. However, scarcity of suitable cadaveric pancreas
      donors is a major limitation that restricts the availability of this therapy to
      millions of diabetic individuals worldwide. Research in the field has therefore
      focused on search for an alternate cell source. Various stem/progenitor cells
      have been considered to be suitable for replacement therapy in diabetes since
      they have the potential to proliferate and differentiate. Over last few years, we
      have specifically focused our attention on understanding the potential of
      progenitor cells that are derived from in vitro expansion of human islets. Since
      epigenetic marks that define an "active" insulin promoter region in beta cells
      are inherited during in vitro expansion, we believe that human islet-derived
      progenitor cells (hIPCs) represent a lineage-committed population of islet
      precursor cells. Here, we describe details of the method for isolation,
      expansion, and characterization of human islet-derived progenitor cells (hIPCs).

PMID- 22610571
TI  - Isolation and characterization of resident mesenchymal stem cells in human
      glomeruli.
AB  - We recently found that human glomeruli deprived of the Bowman's capsule contain a
      population of CD133(-)CD146(+) cells that coexpress the typical mesenchymal stem
      cells (MSCs) markers (such as CD29, CD105, and CD73) and renal specific stem cell
      markers (such us CD24 and Pax2). This population exhibited in vitro self-renewal
      capability, clonogenicity, and multipotency. Beside to osteogenic, adipogenic,
      and chondrogenic differentiation, these cells when cultured in appropriate
      culture conditions were able to differentiate into endothelial cells, epithelial
      cells expressing podocytes markers, and mesangial cells. These populations may
      have a role in the physiological cell turnover and/or in the response to renal
      injury. Herein, we present a review of the experimental procedures used for
      isolation and characterize MSCs resident in human adult glomeruli.

PMID- 22610572
TI  - Endothelial colony-forming progenitor cell isolation and expansion.
AB  - Vessel wall-derived somatic endothelial colony-forming progenitor cells (ECFCs)
      are key players in vascular homeostasis and regeneration. Due to their robust
      proliferative potential and profound vessel-forming capacity, ECFCs are
      considered to represent an attractive tool for vascular regenerative medicine and
      a promising target for antiangiogenic tumor therapy. Here, we describe an easily
      applicable method for isolating ECFCs directly from unmanipulated adult human
      blood and an animal protein-free large-scale expansion system to generate more
      than 100 million functional ECFCs.

PMID- 22610573
TI  - Isolation and characterization of stem cell-enriched human and canine hair
      follicle keratinocytes.
AB  - The epithelial (keratinocyte) stem cells locating at the bulge region of hair
      follicles have been reported to possess high proliferative capacity in vitro and
      multipotency to repopulate hair follicles, sebaceous glands, and the epidermis,
      indicating the importance of those cells for the clinical applications including
      gene therapy and regenerative medicine. However, most of previous investigations
      adopted rodent bulge cells. The biological properties of human and rodent bulge
      cells have been reported to be distinct. Accordingly, it is crucial to directly
      isolate and characterize human bulge cells. However, the supply of human hair
      follicles for investigative purposes may be extremely limited in some situation.
      Dogs share analogous hair loss disorders with humans. Recent investigations have
      uncovered the biological similarities between canine bulge cells, suggesting that
      canine bulge cells are valuable substitute for the biological characterization of
      human bulge cells. Here, we provided the protocols for the isolation and
      characterization of human and canine hair follicle stem cell-enriched
      keratinocytes. Manual microdissection still represents the most commonly used
      technique to enrich bulge cells from human and canine hair follicles. Positive
      selection using a cell surface marker, CD200, should enable further enrichment of
      human bulge cells. Confirmation of successful isolation and molecular and
      cellular biological characterization of bulge cells are possible by real-time PCR
      and flow cytometry analyses described here. Colony-forming assay enables not only
      the evaluation of in vitro proliferative capacity but also the subcloning of
      holoclone keratinocytes, putative keratinocyte stem cells. Finally, hair
      reconstitution assay is available for the assessment of multipotency in vivo and
      sets a basis for tissue engineering of hair follicles.

PMID- 22610574
TI  - Human salivary gland stem cells: isolation, propagation, and characterization.
AB  - Stem cells are of outstanding interest for a variety of applications in
      regenerative medicine. The identification and characterization of novel tissue
      sources in order to reduce donor site morbidity and to provide specific cells in
      clinically applicable numbers have led to the detection of stem cells in almost
      all adult tissues. Salivary glands are of specific interest to our lab, as these
      tissues are easily accessible for the head and neck surgeon with low donor site
      morbidity. On the other hand, they possess an endocrine and exocrine function and
      thus play a very specific role in the human body. Stem cell identity however can
      only be demonstrated using a combination of different methods in vitro, as there
      is not a single marker or feature allowing for definite identification of such
      cells. In this chapter, we provide a comprehensive summary of our experimental
      methods for the isolation and characterization of human salivary gland stem cells
      in vitro.

PMID- 22610575
TI  - Identification, isolation, characterization, and banking of human dental pulp
      stem cells.
AB  - Dental pulp stem cells (DPSCs) can be found within the "cell rich zone" of the
      dental pulp. Their embryonic origin, from neural crests, explains their
      multipotency. Up to now, it has been demonstrated that these cells are capable of
      producing bone tissue, both in vitro and in vivo, as well as a simil-dentin
      tissue, in vitro. In addition, it has been reported that these cells
      differentiate into adipocytes, endotheliocytes, melanocytes, neurons, and glial
      cells and can be easily cryopreserved and stored for long periods of time and
      retain their multipotency and bone-producing capacity. Moreover, recent attention
      has been focused on tissue engineering and on the properties of these cells:
      several scaffolds have been used to promote 3D tissue formation and studies have
      demonstrated that DPSCs show good adherence and bone tissue formation on
      microconcavity surface textures. In addition, adult bone tissue with good
      vascularization has been obtained in grafts. Interestingly, they seem to possess
      immunoprivileges as they can be grafted into allogenic tissues and seem to exert
      anti-inflammatory abilities, like many other mesenchymal stem cells. Their recent
      use in clinical trials for bone repair enforces the notion that DPSCs can be used
      successfully in patients. Therefore, their isolation, selection, differentiation,
      and banking are of great importance. The isolation technique used in most
      laboratories is based on the use of flow cytometry with cell sorter termed FACS
      (fluorescent activated cell sorter). It is now important to obtain new
      methods/protocols to select and isolate stem cells without staining by
      fluorescent markers or use of magnetic beads. These new procedures should be
      based on biophysical differences among the different cell populations in order to
      obtain interesting peculiarities for implementation in biomedical/clinical
      laboratories. It is emphasized that the new methods must address simplicity and
      short times of preparation and use of samples, complete sterility of cells, the
      potential disposable, low cost and complete maintenance of the viability, and
      integrity of the cells with real-time response for subsequent applications in the
      biomedical/clinical/surgical fields.

PMID- 22610576
TI  - Isolation and differentiation potential of fibroblast-like stromal cells derived
      from human skin.
AB  - Isolation of progenitor cell population is the first step in performing stem cell
      research. Progenitors isolated using different methods usually exhibit different
      characteristics and varied differentiation potentials. Here, we describe a method
      for isolation of the multipotent stromal cells from human foreskin tissues. The
      isolation rate is high and the obtained cells could be easily maintained in DMEM
      without supplement with specific growth factors.

PMID- 22610577
TI  - Immortalization of human mesenchymal stromal cells with telomerase and red
      fluorescence protein expression.
AB  - Human mesenchymal stromal cells (hMSCs) play a crucial role in tissue engineering
      and regenerative medicine and thus have important clinical potential for cell
      based therapy. However, the limited cell number and the difficulty in detecting
      these cells in vivo have restricted many hMSC studies. Therefore, the development
      of hMSCs immortalized with telomerase and expressing red fluorescence protein
      will facilitate their expansion and detection in vivo, and these cells will be
      important for both to stem cell research and clinical use. In this chapter, we
      describe the protocols used to establish telomerase- and red fluorescence protein
      expressing immortalized hMSCs using a nonviral transfection method. These cells
      will be useful tools for stem cell research and translational studies.

PMID- 22610578
TI  - Genetic modification of mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSC) are currently considered the most promising type of
      adult stem cells for therapeutic applications, because they can be easily
      isolated from the bone marrow and other tissues, and manipulated for different
      applications. The genetic transformation of MSC using genes that enhance their
      homing ability, as well as their proliferation and survival capacities when
      transplanted to sites of injury, is an important alternative to improve MSC
      function, especially for tissue regeneration. This chapter describes protocols
      for the transformation of MSC using plasmid vectors by lipofection and
      electroporation, as well as retroviral vectors representing viral
      transformations.

PMID- 22610579
TI  - Methodology, biology and clinical applications of human mesenchymal stem cells.
AB  - Stem cells are known by their capacity of self-renewal and differentiation into
      at least one specialized cell type. Mesenchymal stem cells (MSCs) were isolated
      initially from bone marrow but are now known to exist in any vascularized organ
      or tissue in adults. MSCs have a great therapeutic potential, due to their
      ability to migrate to sites of tissue injury and secrete trophic factors that
      hasten endogenous repair. They have also been shown to present immunosuppressive
      properties that may be used in the treatment of autoimmune or graft-versus-host
      diseases. Clinical trials employing MSCs show that the therapy is safe, but the
      efficiency needs to be in tested in phase III and IV studies. We describe here
      protocols for the isolation of human MSCs from human bone marrow and adipose
      tissue. The safe use of these cells demand a thorough in vitro characterization,
      as described in protocols of immunophenotyping by flow cytometry and analysis of
      their capacity to differentiate into adipogenic, osteogenic, and chondrogenic
      lineages.

PMID- 22610580
TI  - In vitro production of enucleated red blood cells from hematopoietic stem and
      progenitor cells.
AB  - The hematopoietic stem cells that are present in bone marrow and umbilical cord
      blood are promising materials for in vitro production of red blood cells (RBCs).
      In particular, umbilical cord blood cells are likely to be readily available
      since they are generally discarded after parturition. Provided the mother of the
      neonate consents to the use of the umbilical cord blood, this material can
      provide a useful resource without any further complicating critical or ethical
      concerns. Here, we describe a method that does not require feeder cells but
      provides an efficient approach to the production of enucleated RBCs from the
      hematopoietic stem and progenitor cells in umbilical cord blood.

PMID- 22610581
TI  - Methods for cancer stem cell detection and isolation.
AB  - The study and investigation of cancer stem cells (CSCs) or tumour initiating
      cells (TICs) have received enormous attention over the 10 years. CSCs are rare,
      quiescent and capable of self-renewing and maintaining tumour growth and
      heterogeneity. Better understanding of CSCs will no doubt lead to a new era of
      both basic and clinical cancer research, reclassification of human tumours and
      development of novel therapeutic strategies. Therefore, the biological properties
      of CSCs, the relevance of CSCs to cancer therapy and methodologies to identify
      them are essential in order to address real and efficacious therapeutic
      strategies to eradicate the cancer. Here, we describe the main protocols to
      identify CSCs starting from primary tumours including glioblastoma, sarcoma, lung
      and breast cancers.

PMID- 22610582
TI  - Biocompatible nanoparticle labeling of stem cells and their distribution in
      brain.
AB  - Nanolabeling is an invaluable novel technique in biology to detect and
      characterize different parts of biological systems including microscopic
      entities, viz., cells inside the living systems. Stem cells (SCs) are multipotent
      cells with the potential to differentiate into bone, cartilage, fat, muscle
      cells, and neurons and are being investigated for their utility in cell-based
      transplantation therapy. Yet, adequate methods to track transplanted SCs in vivo
      are limited, precluding functional studies. Nanoparticles (quantum dots) offer an
      alternative to organic dyes and fluorescent proteins to label and track cells in
      vitro and in vivo. These nanoparticles are resistant to chemical and metabolic
      degradation, demonstrating long-term photo stability. Here, we describe the
      technology of labeling the stem cells with silver nitrate nanoparticles in an in
      vitro coculture model. This is followed by defining the procedure of
      administering these cells in vivo and studying the distribution pattern and
      resultant regenerative effects of the "tagged" stem cells.

PMID- 22610583
TI  - Highlights of the issue 3, 2012.

PMID- 22610584
TI  - The bias of "music-infected consciousness": the aesthetics of listening in the
      laboratory and on the city streets of Fin-de-Siecle Berlin and Vienna.
AB  - Shifts in the psychophysical study of sound sensation reinforced the changing
      status of musical expertise in the nineteenth century. The Carl Stumpf-Wilhelm
      Wundt debate about tone-differentiation experimentation narrowed the conception
      of hearing. For Stumpf, "music consciousness" (Musikbewusstsein) granted the
      experimental subjects exceptional insight into sound sensation. This belief
      reflected a cultural reevaluation of listening, exemplified in music critic
      Eduard Hanslick decrying the scourge of the city: the piano playing of the
      neighbors. Stumpf and Hanslick's defenses of subjective musical expertise both
      inside the laboratory and on the city streets reveal the increasingly divergent
      conceptions of hearing and listening. 

PMID- 22610585
TI  - Effects of aurothiomalate and gold(III) complexes on spontaneous motility of
      isolated human oviduct.
AB  - Organic gold complexes have different biological activity, depending on their
      potential for interactions with key functional molecules.The aim of this study
      was to investigate potential of several newly synthesized organic gold complexes
      to influence spontaneous motility of the Fallopian tubes.The effects of
      [Au(bipy)Cl(2)](+) (dichloride(2,2'-bipyridyl)aurate(III)-ion), aurothiomalate,
      [Au(DMSO)(2)Cl(2)]Cl and DMSO on spontaneous motility of Fallopian tubes were
      tested on the isolated tube segments in vitro. Aurothiomalate (from 2.9 * 10(-9)
      to 4.9 * 10(-4) M/l), [Au(bipy)Cl(2)]Cl (from 3.3 * 10(-9) to 4.2 * 10(-5) M/l)
      and DMSO (from 1.9 * 10(-8) to 1.0 * 10(-5) M/l) did not affect spontaneous
      contractions of the isolated Fallopian tube ampulla, while [Au(DMSO)(2)Cl(2)]Cl
      (from 2.9 * 10(-9) to 4.2 * 10(-5) M/l) showed concentration-dependent increase
      (stimulation) of spontaneous contractions of the isolated Fallopian tube isthmus,
      and remained without effect on the isolated ampulla.The drugs designed as organic
      gold complexes with weaker bonds between the gold itself and organic part of a
      molecule could adversely affect motility of the Fallopian tubes, and
      theoretically fertility of women taking such drugs in their reproductive age.

PMID- 22610586
TI  - Resolving protein interactions and complexes by affinity purification followed by
      label-based quantitative mass spectrometry.
AB  - Label-based quantitative mass spectrometry analysis of affinity purified
      complexes, with its built-in negative controls and relative ease of use, is an
      increasingly popular choice for defining protein-protein interactions and
      multiprotein complexes. This approach, which differentially labels
      proteins/peptides from two or more populations and combines them prior to
      analysis, permits direct comparison of a protein pulldown (e.g. affinity purified
      tagged protein) to that of a control pulldown (e.g. affinity purified tag alone)
      in a single mass spectrometry (MS) run, thus avoiding the variability inherent in
      separate runs. The use of quantitative techniques has been driven in large part
      by significant improvements in the resolution and sensitivity of high-end mass
      spectrometers. Importantly, the availability of commercial reagents and open
      source identification/quantification software has made these powerful techniques
      accessible to nonspecialists. Benefits and drawbacks of the most popular labeling
      based approaches are discussed here, and key steps/strategies for the use of
      labeling in quantitative immunoprecipitation experiments detailed.

PMID- 22610587
TI  - Thermal stability of HfO2-on-GaAs nanopatterns.
AB  - We have evaluated the effect of thermal annealing on the morphology, crystalline
      phase and elemental composition of high-k dielectric HfO(2)-on-GaAs nanopatterns
      at 500-620  degrees C by using atomic force microscopy (AFM), high-resolution
      transmission electron microscopy (HRTEM) and energy dispersive X-ray spectroscopy
      (EDS). While the HfO(2)-GaAs interface continues to be atomically abrupt at 620 
      degrees C, we have found a gradual shrinkage in the pattern linewidth and period
      with increasing temperature. Facet formation triggered by a nanoscale-modulated
      sequence of tensile and compressive stresses on the GaAs substrate, observed at
      620  degrees C, has been attributed to a volumetric expansion of the HfO(2)
      nanostructures, caused by the tetragonal/cubic to monoclinic HfO(2) phase
      transformation and, to a lesser extent, by solid-state diffusion of As into
      HfO(2).

PMID- 22610589
TI  - HBV/D1: a major HBV subgenotype circulating in Uyghur patients with chronic HBV
      infection in Xinjiang, China.
AB  - Each hepatitis B virus (HBV) genotype and subgenotype is associated with a
      particular geographic distribution, ethnicity, and anthropological history. The
      present study investigated the genomic characteristics of HBV from Uyghur
      patients with chronic HBV infection in Xinjiang, China. Among the 53 Uyghur
      patients enrolled, HBV/D was found to be the dominant strain, with 64.2 %
      (34/53), 60.4 % (32/53) with HBV/D1 and 3.8 % (2/53) with HBV/D3. In addition to
      these findings, 3.8 % HBV/B (2/53), 5.7 % HBV/C (3/53), 11.3 % C+D (6/53), 7.5 %
      B+D (4/53), 3.8 % B+C (2/53) and 3.8 % B+C+D (2/53) were also detected. The full
      length genome of seven HBV/D1 isolates and 144 reference sequences retrieved from
      GenBank were compared and analyzed by biological information methods. These
      results demonstrate that the D1 isolates from Xinjiang and Central Asia show a
      close genetic proximity (0.013+/-0.0007). Furthermore, four unique amino acid
      substitutions (sp82(Asn), sp89(His), rt129(Leu), rt151(Leu)) representing
      background polymorphisms rather than drug resistance mutations or immune escape
      variants were found in the Uyghur patients of Xinjiang, but these were seldom
      found in HBV/D1 strains from other regions (0 %-14.3 %). This study indicates
      that in Xinjiang, unlike HBV-infected Han patients, HBV/D1 is the predominant
      strain among HBV-infected Uyghur people. Although genetic distance analysis
      suggests that the HBV/D1 isolates from Xinjiang are closely related to those from
      Central Asia, unique amino acid substitutions suggest independent evolution of
      HBV in the Uyghur patients of Xinjiang.

PMID- 22610590
TI  - The effects of transcranial direct current stimulation with visual illusion in
      neuropathic pain due to spinal cord injury: an evoked potentials and quantitative
      thermal testing study.
AB  - BACKGROUND: Neuropathic pain (NP) is common in spinal cord injury (SCI) patients.
      One of its manifestations is a lowering of pain perception threshold in
      quantitative thermal testing (QTT) in dermatomes rostral to the injury level.
      Transcranial direct current stimulation (tDCS) combined with visual illusion (VI)
      improves pain in SCI patients. We studied whether pain relief with tDCS + VI
      intervention is accompanied by a change in contact heat- evoked potentials
      (CHEPs) or in QTT. METHODS: We examined 18 patients with SCI and NP before and
      after 2 weeks of daily tDCS + VI intervention. Twenty SCI patients without NP and
      14 healthy subjects served as controls. We assessed NP intensity using a
      numerical rating scale (NRS) and determined heat and pain thresholds with thermal
      probes. CHEPs were recorded to stimuli applied at C4 level, and subjects rated
      their perception of evoked pain using NRS during CHEPs. RESULTS: Thirteen
      patients reported a mean decrease of 50% in the NRS for NP after tDCS + VI.
      Evoked pain perception was significantly higher than in the other two groups, and
      reduced significantly together with CHEPs amplitude after tDCS + VI with respect
      to baseline. Pain perception threshold was significantly lower than in the other
      two groups before tDCS + VI intervention, and increased significantly afterwards.
      CONCLUSION: Two weeks of tDCS + VI induced significant changes in CHEPs, evoked
      pain and heat pain threshold in SCI patients with NP. These neurophysiological
      tests might be objective biomarkers of treatment effects for NP in patients with
      SCI.

PMID- 22610591
TI  - Transoral robotic surgery: role in the management of upper aerodigestive tract
      tumors.
AB  - The toxicity associated with concomitant chemoradiation for the management of
      laryngeal and pharyngeal carcinoma has been well documented. Minimally invasive
      surgical techniques offer the potential to extirpate the malignancy as a single
      modality therapy and provide essential information that may direct subsequent
      treatment. In selected patients, radiation doses may be reduced and systemic
      chemotherapy may be withheld after tumor extirpation. Transoral laser
      microsurgery has proven effective, although inability to manipulate and suture
      tissue by this modality limits ablation and reconstruction of extensive defects.
      Transoral robotic surgery is a relatively new technique that provides several
      unique advantages, which include a 3-dimensional magnified view, ability to see
      and work around curves or angles, and the availability of 2 or 3 robotic arms
      that can be used to reconstruct extensive defects using either local, regional,
      or free flaps. Preliminary data suggest that transoral robotic surgery may
      provide a technique for ablation and reconstruction of pharyngeal defects that
      may be superior to other transoral techniques. It may also provide a means for
      personalizing therapy for oropharyngeal and supraglottic carcinoma.

PMID- 22610588
TI  - Exosomes: vesicular carriers for intercellular communication in neurodegenerative
      disorders.
AB  - The intercellular transfer of misfolded proteins has received increasing
      attention in various neurodegenerative diseases characterized by the aggregation
      of specific proteins, as observed in Alzheimer's, Parkinson's and Huntington's
      disease. One hypothesis holds that intercellular dissemination of these
      aggregates within the central nervous system results in the seeded assembly of
      the cognate soluble protein in target cells, similar to that proposed for
      transmissible prion diseases. The molecular mechanisms underlying the
      intercellular transfer of these proteinaceous aggregates are poorly understood.
      Various transfer modes of misfolded proteins including continuous cell-cell
      contacts such as nanotubes, unconventional secretion or microvesicle/exosome
      associated dissemination have been suggested. Cells can release proteins, lipids
      and nucleic acids by vesicular exocytosis pathways destined for horizontal
      transfer. Encapsulation into microvesicular/exosomal vehicles not only protects
      these molecules from degradation and dilution in the extracellular space but also
      facilitates delivery over large distances, e.g. within the blood flow or
      interstitial fluid. Specific surface ligands might allow the highly efficient and
      targeted uptake of these vesicles by recipient cells. In this review, we focus on
      the cell biology and function of neuronal microvesicles/exosomes and discuss the
      evidence for pathogenic intercellular protein transfer mediated by vesicular
      carriers.

PMID- 22610593
TI  - TOR: The ancient link between cancer and ageing? Could ageing and cancer be
      unified by TOR via the 'compromise' struck between soma and germline at the dawn
      of multicellular life?

PMID- 22610592
TI  - Low-dose atorvastatin, losartan, and particularly their combination, provide
      cardiovascular protection in isolated rat heart and aorta.
AB  - Statins and angiotensin receptor blockers at therapeutic doses have beneficial
      cardiovascular effects, which can be applied for cardiovascular protection. We
      explored whether low doses of atorvastatin, losartan, and particularly their
      combination, possess important pleiotropic vasodilatory effects. Wistar rats were
      treated daily with low-dose atorvastatin (2 mg/kg, n = 15), low-dose losartan (5
      mg/kg, n = 15), their combination (n = 15), or saline (n = 15). After 4, 6, or 8
      weeks the animals were anesthetized, blood samples taken, and their hearts and
      thoracic aortas isolated. Two kinds of experiments were performed: the
      measurement of coronary flow rate after ischemia/reperfusion myocardial injury
      and endothelium-dependent relaxation of thoracic aorta. In both models, maximal
      vasodilation activity was obtained in rats treated for 6 weeks. In the
      ischemia/reperfusion myocardial injury model, coronary flow increased
      (atorvastatin or losartan 1.9-fold, P < 0.01; combination 2.4-fold, P < 0.001)
      compared with controls. In the thoracic aorta model, endothelium-dependent
      relaxation significantly increased only in the combination group compared with
      the control group (up to 1.4-fold; P < 0.01). Simultaneously, we detected
      increased anti-inflammatory activity and increased nitric oxide concentration,
      but no changes in lipids and blood pressure. In a rat model we showed important
      vasodilatory activity of low-dose atorvastatin, losartan, and particularly their
      combination. The effects of the low-dose combination were accompanied by, and
      probably at least partly achieved by, anti-inflammatory and nitric oxide
      pathways. Overall, these results could be valuable for the development of new
      vascular protective strategies focusing on a low-dose regimen of statins and
      sartans, and particularly their combination.

PMID- 22610597
TI  - Perceived stress and self-esteem mediate the effects of work-related stress on
      depression.
AB  - The aim of the present study was to investigate the impact of perceived stress
      and self-esteem on work-related stress and depression. Two hundred and eighty
      four Korean nurses participated in the study. The participants completed four
      questionnaires, including the Korean short version of the occupational stress
      scale, the perceived stress scale, the Rosenberg self-esteem scale and the Beck
      depression inventory. Structural equation modelling was used to determine the
      relationships among work-related stress, perceived stress, self-esteem, and
      depression. Work-related stress was positively associated with depression.
      Perceived stress was inversely related to self-esteem and positively associated
      with work-related stress and depression, respectively. Self-esteem was negatively
      associated with work-related stress and depression. Structural equation modelling
      revealed that self-esteem and perceived stress fully mediate the relationship
      between work-related stress and depression. Future studies should further
      investigate the effect of psychological characteristics on work-related stress
      and symptoms of depression.

PMID- 22610598
TI  - Structural analysis of mycolic acids from phenol-degrading strain of Rhodococcus
      erythropolis by liquid chromatography-tandem mass spectrometry.
AB  - We used reversed phase liquid chromatography-electrospray ionization tandem mass
      spectrometry for direct analysis of mycolic acids (MAs) from four different
      cultivations of Rhodococcus erythropolis. This technique enabled us to identify
      and quantify the specific molecular species of MAs directly from lipid extracts
      of the bacterium, including the determination of their basic characteristics such
      as retention time and mass spectra. We identified a total of 60 molecular species
      of MAs by means of LC/MS. In collision-induced dissociation tandem mass
      spectrometry, the [M-H](-) ions eliminated two residues, i.e., meroaldehyde and
      carboxylate anions containing alpha-alkyl chains. The structural information from
      these fragment ions affords structural assignment of the mycolic acids, including
      the lengths and number of double bond(s). Two strains, i.e., R. erythropolis CCM
      2595 and genetically modified strain CCM 2595 pSRK 21 phe were cultivated on two
      different substrates (phenol and phenol with addition of humic acids as a sole
      carbon source). The addition of humic acids showed that there is a marked
      increase of unsaturated mycolic acids, mostly in the range of 20-100 %. This
      effect is more pronounced in the R. erythropolis CCM 2595 strain.

PMID- 22610599
TI  - Highly stretchable and highly conductive metal electrode by very long metal
      nanowire percolation network.
AB  - A highly stretchable metal electrode is developed via the solution-processing of
      very long (>100 MUm) metallic nanowires and subsequent percolation network
      formation via low-temperature nanowelding. The stretchable metal electrode from
      very long metal nanowires demonstrated high electrical conductivity (~9 ohm sq(
      1) ) and mechanical compliance (strain > 460%) at the same time. This method is
      expected to overcome the performance limitation of the current stretchable
      electronics such as graphene, carbon nanotubes, and buckled nanoribbons.

PMID- 22610601
TI  - MALDI-mass spectrometry imaging of desalted rat brain sections reveals ischemia
      mediated changes of lipids.
AB  - Ischemia-mediated lipidomic changes in rat brains were explored by matrix
      assisted laser desorption/ionization-mass spectrometry (MALDI-MS) profiling and
      imaging after in situ desalting which drastically simplified the spectral
      presentation of tissue lipids. Removal of interference from the massively changed
      cations in response to tissue damage permitted the revelation of subtle yet
      important lipidomic changes. The identities of the detected lipids were confirmed
      by MALDI tandem mass spectrometry (MALDI-MS/MS). The MALDI-MS imaging (MALDI-MSI)
      result of lysophosphatidylcholine 16:0 (LPC 16:0) in the desalted brain section
      appeared essentially identical to that of sodiated LPC 16:0 in the adjacent
      undesalted section and verified the suitability of the desalting method for the
      MALDI-MSI studies of lipids in tissue. Other than the consistently decreased
      phosphatidylcholine (PC) 16:0/18:1, images of PCs containing all saturated, or
      combined saturated and monounsaturated fatty acyl (MUFA) residues revealed their
      parenchymal increase by ischemia. Images of PCs containing polyunsaturated fatty
      acyl (PUFA) residues in normal cortex showed laminated patterns similar to
      cortical lamina. Ischemia reduced the abundance of PC 16:0/20:4 and PC 16:0/22:6
      and disrupted the laminated distribution of the former. However, ischemia
      increased the subcortical abundance of PUFA-PCs containing stearoyl residue and
      confined their cortical increase within limited areas. Image of parenchymal
      sphingomyelin 18:0 (SM 18:0) showed its consistent decrease by ischemia that
      paralleled the increase of ceramide 18:0-H(2)O in region of moderate to high SM
      abundance. The above results presented the lipidomic changes largely different
      from previous MALDI-MSI results and suggested a window of intervention that may
      benefit the management of cerebrovascular accident and other brain injuries.

PMID- 22610600
TI  - Effect of replacing soybean protein by taro leaf (Colocasia esculenta (L.)
      Schott) protein on growth performance of exotic (Landrace * Yorkshire) and native
      (Moo Lath) Lao pigs.
AB  - The impact of replacing soybean crude protein (CP) with CP from ensiled taro
      leaves (ET) on growth performance, carcass traits, and organ weights in Landrace
      * Yorkshire (LY) and Moo Lath (ML) Lao pigs was studied. Twenty-four castrated
      male pigs, 12 of each breed, were allocated to the treatments according to a
      completely randomized 3 * 2 factorial (three levels of ET * two breeds)
      arrangement with four pigs per treatment. The pigs were kept in individual pens
      and were fed at 4 % dry matter of body weight for 105 days. The control diet
      (ET0) was formulated with soybean meal as the main CP source, and in the other
      two diets, soybean CP was replaced to 25 % (ET25) and 50 % (ET50), respectively,
      with CP from ensiled taro leaves. Calculated metabolizable energy intake
      decreased with increasing replacement of soybean CP in the diet, while dry matter
      intake (DMI), CP intake (CPI), average daily gain (ADG), and feed conversion
      ratio (FCR) were unaffected. Carcass weight, back fat thickness, and dressing
      percentage were unaffected by soybean CP replacement, while organ weights (except
      for spleen) increased (P < 0.001) when soybean CP was replaced by CP from ensiled
      taro leaves in the diet. LY pigs had higher (P < 0.001) DMI, CPI, and ADG and
      better (P < 0.001) FCR than ML pigs. LY pigs had higher carcass weight (P <
      0.001), lower back fat thickness (P < 0.001), and higher organ weights (P < 0.05
      0.001) than the ML pigs. In conclusion, taro leaf silage can replace up to 50 %
      of soybean CP in the diet of growing Lao LY and ML pigs without negative effects
      on performance and carcass traits.

PMID- 22610602
TI  - Simultaneous determination of triazole antifungal drugs in human plasma by
      sweeping-micellar electrokinetic chromatography.
AB  - The number of cases of invasive fungal infections (IFIs) has risen significantly
      in recent years; therefore, this study developed a sensitive and effective
      sweeping-micellar electrokinetic chromatography (MEKC) method for the
      simultaneous determination of the three most frequently used triazole antifungal
      drugs for the treatment of IFIs, which included voriconazole, itraconazole, and
      posaconazole. Due to the diverse lipophilicity of the tested drugs, the
      analytical conditions that resulted in good resolution between itraconazole and
      posaconazole caused the peak for voriconazole to split. The splitting phenomenon
      was resolved by incorporating a high-salt stacking mechanism into the sweeping
      MEKC method. The optimum background electrolyte was composed of 25 mM phosphoric
      acid solution (pH 2.2), 100 mM sodium dodecyl sulfate, 13 % acetonitrile, and 13
      % tetrahydrofuran. The best peak shape of voriconazole was obtained when the
      conductivity ratio between the sample matrix and background electrolyte was 2.3.
      Compared to the conventional MEKC mode, the enhancement factor of the sweeping
      MEKC method was 66 for itraconazole, 55 for posaconazole, and 43 for
      voriconazole. The sweeping-MEKC method was validated in terms of precision,
      accuracy, linearity, specificity, selectivity, and sensitivity. The linearity
      ranges of the method covered the commonly used therapeutic ranges of the three
      drugs. The developed sweeping-MEKC method was successfully applied to the
      analysis of clinical samples, thus demonstrating its applicability for clinical
      use.

PMID- 22610603
TI  - Development of SI-traceable C-peptide certified reference material NMIJ CRM 6901
      a using isotope-dilution mass spectrometry-based amino acid analyses.
AB  - A certified reference material (CRM) is a higher-order calibration material used
      to enable a traceable analysis. This paper describes the development of a C
      peptide CRM (NMIJ CRM 6901-a) by the National Metrology Institute of Japan using
      two independent methods for amino acid analysis based on isotope-dilution mass
      spectrometry. C-peptide is a 31-mer peptide that is utilized for the evaluation
      of beta-cell function in the pancreas in clinical testing. This CRM is a
      lyophilized synthetic peptide having the human C-peptide sequence, and contains
      deamidated and pyroglutamylated forms of C-peptide. By adding water (1.00 +/-
      0.01) g into the vial containing the CRM, the C-peptide solution in 10 mM
      phosphate buffer saline (pH 6.6) is reconstituted. We assigned two certified
      values that represent the concentrations of total C-peptide (mixture of C
      peptide, deamidated C-peptide, and pyroglutamylated C-peptide) and C-peptide. The
      certified concentration of total C-peptide was determined by two amino acid
      analyses using pre-column derivatization liquid chromatography-mass spectrometry
      and hydrophilic chromatography-mass spectrometry following acid hydrolysis. The
      certified concentration of C-peptide was determined by multiplying the
      concentration of total C-peptide by the ratio of the relative area of C-peptide
      to that of the total C-peptide measured by liquid chromatography. The certified
      value of C-peptide (80.7 +/- 5.0) mg/L represents the concentration of the
      specific entity of C-peptide; on the other hand, the certified value of total C
      peptide, (81.7 +/- 5.1) mg/L can be used for analyses that does not differentiate
      deamidated and pyroglutamylated C-peptide from C-peptide itself, such as amino
      acid analyses and immunochemical assays.

PMID- 22610604
TI  - Photomorphogenesis--from one photoreceptor to 14: 40 years of progress.

PMID- 22610606
TI  - The reference dose for subchronic exposure of pigs to cadmium leading to early
      renal damage by benchmark dose method.
AB  - Pigs were exposed to cadmium (Cd) (in the form of CdCl(2)) concentrations ranging
      from 0 to 32mg Cd/kg feed for 100 days. Urinary cadmium (U-Cd) and blood cadmium
      (B-Cd) levels were determined as indicators of Cd exposure. Urinary levels of
      beta(2)-microglobulin (beta(2)-MG), alpha(1)-microglobulin (alpha(1)-MG), N
      acetyl-beta-D-glucosaminidase (NAG), cadmium-metallothionein (Cd-MT), and retinol
      binding protein (RBP) were determined as biomarkers of tubular dysfunction. U-Cd
      concentrations were increased linearly with time and dose, whereas B-Cd reached
      two peaks at 40 days and 100 days in the group exposed to 32mg Cd/kg. Hyper
      metallothionein-urinary (HyperMTuria) and hyper-N-acetyl-beta-D-glucosaminidase
      urinary (hyperNAGuria) emerged from 80 days onwards in the group exposed to 32mg
      Cd/kg feed, followed by hyper-beta2-microglobulin-urinary (hyperbeta2-MGuria) and
      hyper-retinol-binding-protein-urinary (hyperRBPuria) from 100 days onwards. The
      relationships between the Cd exposure dose and biomarkers of exposure (as well as
      the biomarkers of effect) were examined, and significant correlations were found
      between them (except for alpha(1)-MG). Dose-response relationships between Cd
      exposure dose and biomarkers of tubular dysfunction were studied. The critical
      concentration of Cd exposure dose was calculated by the benchmark dose (BMD)
      method. The BMD(10)/BMDL(10) was estimated to be 1.34/0.67, 1.21/0.88, 2.75/1.00,
      and 3.73/3.08mg Cd/kg feed based on urinary RBP, NAG, Cd-MT, and beta(2)-MG,
      respectively. The calculated tolerable weekly intake of Cd for humans was 1.4
      MUg/kg body weight based on a safety factor of 100. This value is lower than the
      currently available values set by several different countries. This indicates a
      need for further studies on the effects of Cd and a re-evaluation of the human
      health risk assessment for the metal.

PMID- 22610607
TI  - Acute acetaminophen intoxication leads to hepatic iron loading by decreased
      hepcidin synthesis.
AB  - Acetaminophen (APAP), a major cause of acute liver injury in the Western world,
      is mediated by metabolism and oxidative stress. Recent studies have suggested a
      role for iron in potentiating APAP-induced liver injury although its regulatory
      mechanism is not completely understood. The current study was designed to unravel
      the iron-regulating pathways in mice after APAP-induced hepatotoxicity. Mice with
      severe injury showed a significant increase in liver iron concentration and
      oxidative stress. Concurrently, the plasma concentration of hepcidin, the key
      regulator in iron metabolism, and hepatic hepcidin antimicrobial peptide (Hamp)
      mRNA expression levels were significantly reduced. We showed that hepcidin
      transcription was inhibited via several hepcidin-regulating factors, including
      the bone morphogenetic protein/small mother against decapentaplegic (BMP/SMAD)
      pathway, CCAAT/enhancer-binding protein alpha (C/EBPalpha), and possibly also via
      erythropoietin (EPO). Downregulation of the BMP/SMAD signaling pathway was most
      likely caused by hypoxia-inducible factor 1alpha (HIF-1alpha), which was
      increased in mice with severe APAP-induced liver injury. HIF-1alpha stimulates
      cleaving of hemojuvelin, the cofactor of the BMP receptor, thereby blocking BMP
      induced signaling. In addition, gene expression levels of C/ebpalpha were
      significantly reduced, and Epo mRNA expression levels were significantly
      increased after APAP intoxication. These factors are regulated through HIF-1alpha
      during oxidative stress and suggest that HIF-1alpha is a key modulator in reduced
      hepcidin transcription after APAP-induced hepatotoxicity. In conclusion, acute
      APAP-induced liver injury leads to activation of HIF-1alpha, which results in a
      downregulation in hepcidin expression through a BMP/SMAD signaling pathway and
      through C/EBPalpha inhibition. Eventually, this leads to hepatic iron loading
      associated with APAP cytotoxicity.

PMID- 22610605
TI  - Cadmium-induced proteome remodeling regulated by Spc1/Sty1 and Zip1 in fission
      yeast.
AB  - Stress-activated protein kinases and transcription factors are crucial for
      surviving exposure to cadmium and other environmental toxicants, but their
      effects on the proteome remain largely unexplored. In this study, isobaric tag
      for relative and absolute quantitation reveals that cadmium stress triggers rapid
      proteome remodeling in the fission yeast Schizosaccharomyces pombe. Spc1/Sty1, a
      mitogen/stress-activated protein kinase homologous to human p38 and Saccharomyces
      cerevisiae Hog1, controls many of these changes, including enzymes of the
      oxidative phase of the pentose phosphate pathway and trehalose metabolism.
      Genetic studies indicate that control of carbohydrate metabolism by Spc1 is
      required for cadmium tolerance. The bZIP transcription factor Zip1, which is
      functionally related to human Nrf2 and S. cerevisiae Met4, has a smaller effect
      on cadmium-induced proteome remodeling, but it is required for production of key
      proteins involved in sulfur metabolism, which are essential for cadmium
      resistance. These studies reveal how Spc1 and Zip1 independently reshape the
      proteome to modulate cellular defense mechanisms against the toxic effects of
      cadmium.

PMID- 22610608
TI  - Chronic exposure to acrylamide induces DNA damage in male germ cells of mice.
AB  - Acrylamide is a reproductive toxicant that has been detected in foods such as
      potato chips and breads. The consequences of chronic exposure to acrylamide in
      the human diet are unknown; however, rodent experiments have shown that acute
      acrylamide exposure in males can lead to decreased fertility and dominant
      lethality. One of the possible mechanisms by which acrylamide elicits these
      effects is thought to be related to its metabolic conversion to glycidamide,
      which can form DNA adducts. To determine whether chronic acrylamide exposure
      produces genetic damage in male germ cells in vivo, male mice were subjected to
      acrylamide through their drinking water. Acrylamide was administered at 0.001,
      0.01, 0.1, 1, and 10 ug/ml for up to 1 year, which was equivalent to 0.0001-2
      mg/kg bodyweight/day. At 1, 3, 6, 9, and 12 months, early male germ cells were
      assessed for DNA damage using a Comet assay modified to detect adducts and
      gammaH2A.X expression, a marker of double-strand breaks. Acrylamide treatment did
      not significantly affect mouse or testis weight, and no gross morphological
      effects were observed in the testis. However, a significant dose-dependent
      increase in DNA damage was observed in germ cells following 6 months of exposure
      in the two highest dosage groups (1 and 10 ug/ml). After 12 months of exposure,
      increases in damage were detected at doses as low as 0.01 ug/ml (0.001 mg/kg
      bodyweight/day). The results of this study are the first to demonstrate that
      chronic exposure to acrylamide, at doses equivalent to human exposures, generates
      DNA damage in male germ cells of mice.

PMID- 22610609
TI  - Subchronic oral exposure to benzo(a)pyrene leads to distinct transcriptomic
      changes in the lungs that are related to carcinogenesis.
AB  - We have previously shown that acute oral exposure to the environmental carcinogen
      benzo(a)pyrene (BaP) elicits comparable levels of DNA adducts, but distinct
      transcriptomic changes, in mouse lungs and livers, the two main BaP bioactivating
      organs. Oral BaP exposure is predominantly associated with lung cancer and not
      hepatic cancer in some animal models, suggesting that gene expression differences
      may provide insight into the drivers of tissue-specific carcinogenesis. In the
      present study, we examine pulmonary DNA adduct formation, lacZ mutant frequency,
      and mRNA profiles in adult male MutaMouse following subchronic (28 day) oral
      exposure to BaP (0, 25, 50, and 75 mg/kg/day) and sacrificed 3 days postexposure.
      The results are compared with those obtained from livers of the same mice
      (previously published). Although there was a 1.8- to 3.3-fold increase in the
      levels of DNA adducts in lung compared with liver, the lacZ transgene mutant
      frequency was similar in both tissues. At the transcriptomic level, a transition
      from activation of the DNA damage response p53 pathway at the low dose to the
      induction of genes involved in angiogenesis, evasion of apoptosis and growth
      signals at the high doses was evident only in the lungs. These results suggest
      that tissue DNA adducts and mutant frequency are sensitive markers of target
      tissue exposure and mode of action, whereas early changes in gene expression may
      provide a better indication of the likelihood of carcinogenic transformation in
      selected tissues. Moreover, the study provides new information on the underlying
      mechanisms that contribute to tissue-specific responses to BaP.

PMID- 22610610
TI  - Metabolism of methyleugenol in liver microsomes and primary hepatocytes: pattern
      of metabolites, cytotoxicity, and DNA-adduct formation.
AB  - Methyleugenol (1) is a constituent of many foods, in particular of herbal spices,
      and is used as flavoring agent in foodstuffs and as fragrance in cosmetics. 1 has
      been found to be carcinogenic in rodents, its metabolite, 1-hydroxymethyleugenol
      (2) acting as proximate DNA-binding carcinogen. We incubated 1 with liver
      microsomes of rat, bovine, and human origin. We found 2, 3
      hydroxymethylisoeugenol (3), and 6-hydroxymethyleugenol (4) as major metabolites,
      and 1-oxomethyleugenol (5), 3-oxomethylisoeugenol (6), eugenol (9), chavibetol
      (11), and (RS)-2,3-dihydroxy-2,3-dihydromethyleugenol (7) as minor metabolites.
      Methyleugenol-2,3-epoxide (8), probably the precursor of 7, could not be
      detected. Incubations with synthetic metabolites were applied in order to uncover
      metabolic pathways. Incubations with primary rat hepatocytes revealed mainly
      nonconjugated 2 and conjugated 4, and minor amounts of partly conjugated 7 and
      conjugated 9 + 11. The "reactive metabolites" 3, 5, 6, and 8 were not detectable,
      possibly due to rapid reaction with cellular macromolecules. The highest
      cytotoxicity (resazurin reduction assay and lactate dehydrogenase leakage assay)
      was observed for the main metabolite 2 and its secondary metabolite 5 with EC(50)
      values of 50 and 10 uM, respectively. Deoxyadenosine or deoxyguanosine adducts
      were formed by incubating 1 or metabolites with rat hepatocytes. The rank order
      of adduct formation was 2 > 1 > 3 > 6, whereas 4, 5, and 8 were inactive. In
      conclusion, we present a virtually complete pattern of microsomal (rat, bovine,
      and human) and hepatocellular (rat) metabolites of 1 suggesting the formation of
      several reactive metabolites possibly involved in carcinogenicity, organ
      toxicity, and immune reactions.

PMID- 22610611
TI  - Endothelial dysfunction in normal and prediabetic rats with metabolic syndrome
      exposed by oral gavage to carbon black nanoparticles.
AB  - Exposure to nanosized particles may increase the risk of cardiovascular diseases
      by endothelial dysfunction, particularly in susceptible subjects with metabolic
      syndrome. We investigated vasomotor dysfunction in aorta from obese and lean
      Zucker rats after oral exposure to nanosized carbon black (CB). Rats were exposed
      to 1 or 10 weekly doses of 0, 0.064, 0.64 or 6.4 mg/kg bodyweight and sacrificed
      24 h or 13 weeks later. The exposure to 10 doses of 0.064 or 0.64 mg/kg reduced
      the acetylcholine-induced vasorelaxation in the lean and obese rats. The half
      maximal effect concentration values increased by twofold (95% CI: 1.1-3.5-fold)
      and fourfold (95% CI: 2.3-6.9-fold) in the rats exposed to 0.064 and 0.64 mg/kg
      compared with the controls, respectively. The rats exposed to 10 doses of 0.64
      mg/kg had also 20% (95% CI: 10-29%) lower maximal effect value compared with the
      controls. However, the nitroglycerin-induced vasorelaxation and phenylephrine
      induced vasocontraction was not affected in rats exposed to CB. The endothelial
      dysfunction was not observed in rats sacrificed 13 weeks after the last CB
      exposure. There was unaltered expression of Chrm3, Nos3, Nos2, Ccl2, and Hmox1 in
      aorta tissue of CB-exposed rats. In conclusion, repeated oral exposure to CB was
      associated with endothelial dysfunction in rats, further aggravating the effect
      of metabolic syndrome.

PMID- 22610612
TI  - Urinary biomarker detection of melamine- and cyanuric acid-induced kidney injury
      in rats.
AB  - Oral coexposure of rats to melamine (MEL) and cyanuric acid (CYA) results in a
      dose-dependent increase in the formation of MEL-CYA crystals in the kidney. The
      aim of this study was to determine if urinary biomarkers of acute kidney injury
      could be used to noninvasively detect renal damage associated with crystal
      formation in the kidneys of MEL- and CYA-exposed rats. Urine was obtained on days
      0 (predose), 2, 4, 14, and 28 from male and female Fischer 344 rats fed a diet
      supplemented with 0, 120, 180, or 240 ppm each of MEL and CYA. A number of
      urinary protein biomarkers (kidney injury molecule-1, neutrophil gelatinase
      associated lipocalin, osteopontin, albumin, alpha-GST, GST-Yb1, renal papillary
      antigen 1 [RPA-1], and clusterin) were measured using a multiplex assay system.
      The results showed that RPA-1 (distal tubule and collecting duct injury
      biomarker) was elevated on day 28 at the 120 ppm dose and higher in male rats and
      at the 180 ppm dose and higher in female rats; however, other urinary protein
      biomarkers were significantly elevated only at the 240 ppm dose. Significant
      elevation in blood urea nitrogen and serum creatinine levels, and severe renal
      damage evidenced by histopathology, were observed after 28 days of exposure to
      the highest dose, despite the fact that MEL-CYA crystals were observable at the
      120 and 180 ppm doses. These data indicate that RPA-1 may serve as a noninvasive
      urinary biomarker for the detection and monitoring of obstructive nephropathy
      associated with MEL-CYA exposure.

PMID- 22610613
TI  - Predicting methicillin resistance among community-onset Staphylococcus aureus
      bacteremia patients with prior healthcare-associated exposure.
AB  - To develop and validate prediction rules to identify the risk of methicillin
      resistant Staphylococcus aureus (MRSA) infection among community patients who
      have healthcare-associated (HA) exposure and S. aureus bacteremia. A total of
      1,166 adults with community-onset S. aureus bacteremia were retrospectively
      enrolled. The background prevalence of community MRSA infection was extrapolated
      from 392 community-associated S. aureus bacteremia (CA-SAB) patients without HA
      exposure. Complete and clinical risk scores were derived and tested using data
      from 774 healthcare-associated S. aureus bacteremia (HA-SAB) patients. The risk
      scores were modeled with and without incorporating previous microbiological data
      as a model predictor and stratified patients to low-, intermediate-, and high
      risk groups for MRSA infection. The clinical risk score included five independent
      predictors and the complete risk score included six independent predictors. The
      clinical and complete risk scores stratified 32.7 % and 42.0 % of HA-SAB patients
      to the low-risk group for MRSA infection respectively. The prevalence of MRSA
      infection in score-stratified low-risk groups ranged from 16.3 % to 23.3 %,
      comparable to that of CA-SAB patients (13.8 %). Simple decision rules allow
      physicians to stratify the risk of MRSA infection when treating community
      patients with prior HA exposure and possible S. aureus infection.

PMID- 22610614
TI  - Sonographic antenatal diagnosis of congenital dacryocystoceles.
AB  - Congenital dacryocystoceles are a relatively rare variant of nasolacrimal duct
      obstruction, accounting for only 0.1% of infants with congenital nasolacrimal
      duct obstruction. We report a new case of bilateral congenital dacrocystoceles
      diagnosed in an otherwise uncomplicated fetal ultrasound examination during the
      33rd week of pregnancy. The diagnosis was confirmed postnatally. The neonate, who
      did not present postpartum respiratory distress, was scheduled for endoscopic
      marsupialization-probing of the cystic structures. Parents must be well informed
      about the risk of respiratory distress, and facial appearance. Complete
      resolution is achieved after surgical intervention.

PMID- 22610615
TI  - An introduction to plant cell culture: the future ahead.
AB  - Plant cell, tissue, and organ culture (PTC) techniques were developed and
      established as an experimental necessity for solving important fundamental
      questions in plant biology, but they currently represent very useful
      biotechnological tools for a series of important applications such as commercial
      micropropagation of different plant species, generation of disease-free plant
      materials, production of haploid and doublehaploid plants, induction of
      epigenetic or genetic variation for the isolation of variant plants, obtention of
      novel hybrid plants through the rescue of hybrid embryos or somatic cell fusion
      from intra- or intergeneric sources, conservation of valuable plant germplasm,
      and is the keystone for genetic engineering of plants to produce disease and pest
      resistant varieties, to engineer metabolic pathways with the aim of producing
      specific secondary metabolites or as an alternative for biopharming. Some other
      miscellaneous applications involve the utilization of in vitro cultures to test
      toxic compounds and the possibilities of removing them (bioremediation),
      interaction of root cultures with nematodes or mycorrhiza, or the use of shoot
      cultures to maintain plant viruses. With the increased worldwide demand for
      biofuels, it seems that PTC will certainly be fundamental for engineering
      different plants species in order to increase the diversity of biofuel options,
      lower the price marketing, and enhance the production efficiency. Several aspects
      and applications of PTC such as those mentioned above are the focus of this
      edition.

PMID- 22610616
TI  - History of plant tissue culture.
AB  - Plant tissue culture, or the aseptic culture of cells, tissues, organs, and their
      components under defined physical and chemical conditions in vitro, is an
      important tool in both basic and applied studies as well as in commercial
      application. It owes its origin to the ideas of the German scientist, Haberlandt,
      at the beginning of the twentieth century. The early studies led to root
      cultures, embryo cultures, and the first true callus/tissue cultures. The period
      between the 1940s and the 1960s was marked by the development of new techniques
      and the improvement of those that were already in use. It was the availability of
      these techniques that led to the application of tissue culture to five broad
      areas, namely, cell behavior (including cytology, nutrition, metabolism,
      morphogenesis, embryogenesis, and pathology), plant modification and improvement,
      pathogen-free plants and germplasm storage, clonal propagation, and product
      (mainly secondary metabolite) formation, starting in the mid-1960s. The 1990s saw
      continued expansion in the application of the in vitro technologies to an
      increasing number of plant species. Cell cultures have remained an important tool
      in the study of basic areas of plant biology and biochemistry and have assumed
      major significance in studies in molecular biology and agricultural biotechnology
      in the twenty-first century. The historical development of these in vitro
      technologies and their applications is the focus of this chapter.

PMID- 22610617
TI  - Callus, suspension culture, and hairy roots. Induction, maintenance and
      characterization.
AB  - The growth is a characteristic of each culture and it is determinate by the
      origin of the species, culture conditions, and type of culture. In this chapter,
      we make a comparison of the different growth parameters among three different
      species and three different types of cultures.

PMID- 22610618
TI  - Growth measurements: estimation of cell division and cell expansion.
AB  - The main parameters for the estimation of growth within in vitro cultures are
      reviewed. Procedures to measure these parameters are described, emphasizing in
      each case their convenience of use, depending on the features of the culture
      evaluated.

PMID- 22610619
TI  - Measurement of cell viability.
AB  - An overview of the methods for assessing cell viability is presented. Different
      protocols of the most commonly used assays are described in detail so that the
      readers may be able to determine which assay is suitable for their own projects
      in plant biotechnology.

PMID- 22610620
TI  - Pathogen and biological contamination management in plant tissue culture:
      phytopathogens, vitro pathogens, and vitro pests.
AB  - The ability to establish and grow plant cell, organ, and tissue cultures has been
      widely exploited for basic and applied research, and for the commercial
      production of plants (micro-propagation). Regardless of whether the application
      is for research or commerce, it is essential that the cultures be established in
      vitro free of biological contamination and be maintained as aseptic cultures
      during manipulation, growth, and storage. The risks from microbial contamination
      are spurious experimental results due to the effects of latent contaminants or
      losses of valuable experimental or commercial cultures. Much of the emphasis in
      culture contamination management historically focussed on the elimination of
      phytopathogens and the maintenance of cultures free from laboratory contamination
      by environmental bacteria, fungi (collectively referred to as "vitro pathogens",
      i.e. pathogens or environmental micro-organisms which cause culture losses), and
      micro-arthropods ("vitro pests"). Microbial contamination of plant tissue
      cultures is due to the high nutrient availability in the almost universally used
      Murashige and Skoog (Physiol Plant 15:473-497, 1962) basal medium or variants of
      it. In recent years, it has been shown that many plants, especially perennials,
      are at least locally endophytically colonized intercellularly by bacteria. The
      latter, and intracellular pathogenic bacteria and viruses/viroids, may pass
      latently into culture and be spread horizontally and vertically in cultures.
      Growth of some potentially cultivable endophytes may be suppressed by the high
      salt and sugar content of the Murashige and Skoog basal medium and suboptimal
      temperatures for their growth in plant tissue growth rooms. The management of
      contamination in tissue culture involves three stages: disease screening (syn.
      disease indexing) of the stock plants with disease and endophyte elimination
      where detected; establishment and pathogen and contaminant screening of
      established initial cultures; observation, random sampling, and culture screening
      for micro-organism in multiplication and stored cultures. The increasing
      accessibility of both broad-spectrum and specific molecular diagnostics has
      resulted in advances in multiple pathogen and latent contaminant detection. The
      hazard analysis critical control point management strategy for tissue culture
      laboratories is underpinned by staff training in aseptic technique and good
      laboratory practice.

PMID- 22610621
TI  - Cryopreservation of embryogenic cell suspensions by encapsulation-vitrification
      and encapsulation-dehydration.
AB  - Encapsulation-vitrification and encapsulation-dehydration are two newly developed
      techniques for cryopreservation of embryogenic cell suspensions. Here, we
      describe the two protocols using grapevine (Vitis) as a model plant. Cell
      suspensions at the exponential growth stage cultured in a cell suspension
      maintenance medium are encapsulated to form beads, each being about 4 mm in
      diameter and containing 25% cells. In the encapsulation-vitrification procedure,
      the beads are stepwise precultured in increasing concentrations of sucrose medium
      up to 0.75 M, with 1 day for each concentration. The precultured beads are
      treated with a loading solution for 60 min and then dehydrated with plant
      vitrification solution 2 at 0 degrees C for 270 min before a direct immersion in
      liquid nitrogen. Following cryostorage, the beads are rapidly rewarmed at 40
      degrees C for 3 min and then unloaded with 1 M sucrose solution for 30 min. In
      the encapsulation-dehydration procedure, the beads are precultured in increasing
      concentrations of sucrose medium up to 1 M, with 1 day for each concentration,
      and then maintained on 1 M sucrose medium for 3 days. The precultured beads are
      dehydrated for 6 h under a sterile air flow, prior to rapid freezing in liquid
      nitrogen. The freezing and rewarming procedures are the same as used in the
      encapsulation-vitrification technique. The unloaded beads from encapsulation
      vitrification and rewarmed beads from encapsulation-dehydration are postcultured
      on a recovery medium for 3 days at 25 degrees C in the dark for survival.
      Surviving cells are transferred to a regrowth medium to induce cell
      proliferation. Embryogenic cell suspensions are reestablished by suspending the
      cells in a cell suspension maintenance medium maintained on a gyratory shaker at
      25 degrees C in the dark. For plant regeneration, surviving cells are transferred
      from the recovery medium to an embryo maturation medium and maintained at 25
      degrees C under light conditions. Embryos at the torpedo stage are cultured on a
      rooting medium until whole plantlet regenerates.

PMID- 22610622
TI  - The study of in vitro development in plants: general approaches and photography.
AB  - Careful examination of how explants react to experimental conditions is the first
      step of a successful research program. Photographing the specimen is an extremely
      important method that can be used to document changes of an explant throughout an
      experiment. This article serves to draw attention to the utility of macroscopic
      and microscopic examinations in the study of in vitro development, and details
      some useful methods in the study of the cultured explants.

PMID- 22610623
TI  - Use of statistics in plant biotechnology.
AB  - Statistics and experimental design are important tools for the plant
      biotechnologist and should be used when planning and conducting experiments as
      well as during the analysis and interpretation of results. This chapter provides
      some basic concepts important to the statistical analysis of data obtained from
      plant tissue culture or biotechnology experiments, and illustrates the
      application of common statistical procedures to analyze binomial, count, and
      continuous data for experiments with different treatment factors as well as
      identifying trends of dosage treatment factors.

PMID- 22610624
TI  - Tissue culture methods for the clonal propagation and genetic improvement of
      Spanish red cedar (Cedrela odorata).
AB  - The choice of a method to culture red cedar tissues depends on the final
      objectives pursued. If homogeneous clonal material is required for experimental
      purposes, the easiest way is to generate the lines through adventitious shoot
      induction from seedlings germinated from seeds. If the objective is to generate
      high yielding material for plantation purposes, the choice will be the same
      method but starting from mature vegetative tissues from selected elite plants.
      Most of the process are the same, but the initial steps are less efficient and
      much more elaborate. If the purpose is to generate lines with new genetic
      characteristics through somaclonal variation, mutagenesis, or genetic
      transformation, somatic embryogenesis will be required. No single method in its
      present form is suitable for all purposes. Eventually, the efficient production
      of somatic embryos from rejuvenated shoots collected from mature selected plants
      is the ideal way to culture this species, but for the time being we have to
      choose one or the other. In this chapter, we present a grafting procedure to
      rejuvenate and maintain mother plants in the greenhouse and the in vitro culture
      systems we have developed for the production of Cedrela odorata propagules using
      explants from both young seedlings and mature tissues from selected old trees.
      Using a modified TY17 medium and the BioMINT((r)) temporary immersion system, we
      obtained high multiplication and ex vitro transplantation rates for efficient
      large-scale propagation of this species.

PMID- 22610625
TI  - Micropropagation of banana.
AB  - Banana (Musa spp. AAA) is propagated vegetatively and can be rapidly and
      efficiently propagated by micropropagation. Conventional micropropagation
      techniques, however, may be too costly for commercial purposes. Our laboratory
      has found that depending on the combination of culture vessel and gelling agent
      more economic methods can be chosen for successfully micropropagating banana.

PMID- 22610626
TI  - Liquid in vitro culture for the propagation of Arundo donax.
AB  - We describe a simple and inexpensive plant micropropagation system for giant reed
      (Arundo donax L.) that uses axillary buds from the lateral stems of elite plants
      selected from field- or nursery-grown plants. The buds, attached to the stems are
      cultured in stationary liquid MS culture medium, supplemented with indole 3
      acetic acid and kinetin. This formulation is the only one required for all the
      stages. Contrary to what happens in semisolid medium where roots are not formed,
      the plants cultured in liquid medium are whole plants with shoots and roots that
      develop at the same time. The survival rate of these plants when transferred to
      soil is close to 100% during acclimatization. A clonal line of 900 plants from a
      single mother plant can be produced in 4 months.

PMID- 22610627
TI  - Production of haploids and doubled haploids in maize.
AB  - The in vivo haploid induction approach offers several advantages compared to the
      in vitro induction approach and recurrent self-pollination. It is currently the
      method of choice for inbred line development in many commercial maize breeding
      programs. Here, we describe the in vivo approach for generation of maternal
      doubled haploids (DHs). It involves four steps: (1) induction of haploidy by
      pollinating source germplasm with pollen of a haploid inducer; (2) identification
      of putative haploid seeds (seeds with a haploid embryo) using a seed coloration
      marker system; (3) doubling of chromosomes of putative haploids by treating
      seedlings with a mitotic inhibitor; and (4) verification of putative doubled
      haploids with a stalk color marker and self-pollination of true doubled haploid
      plants to multiply their seed.

PMID- 22610628
TI  - Maize somatic embryogenesis: recent features to improve plant regeneration.
AB  - Plant regeneration capacity is maintained through the life of a plant by the stem
      cell niche present in the meristems. Stem cells are capable of differentiating
      into any plant organ, allowing propagation of new plants by different techniques.
      Among them, somatic embryogenesis is a widely used technique characterized by a
      complex process that involves coordinated expression of genes, mediated by the
      influence of specific hormones, nutrients, stress, and/or environmental signals.
      This tool is particularly relevant in the propagation of genetically improved
      crops. The intrinsic embryogenic potential of the explant used as starting
      material for plant in vitro cultures varies depending on the genotype of each
      plant species. Particularly in maize, the regeneration capacity is lost during
      the course of tissue maturation, since embryogenic callus (E) is almost
      exclusively obtained from immature zygotic embryos. In this chapter, the latest
      advances in the literature for maize somatic embryogenesis process are reviewed.
      Further, a detailed procedure for maize plant regeneration from E callus is
      described. The callus obtained from immature zygotic embryos is capable to
      generate somatic embryos that germinate and develop into fertile normal plants.

PMID- 22610629
TI  - Improved shoot regeneration from root explants using an abscisic Acid-containing
      medium.
AB  - Arabidopsis thaliana is an excellent experimental system to study various aspects
      of plant biology. An efficient regeneration protocol of the plant is important to
      produce in vitro fertile plants, as well as a fundamental step to study the
      cellular, physiological, and molecular mechanisms of plant development. Here, we
      describe an efficient and fast regeneration system from root explants of A.
      thaliana ecotypes Columbia-0 and Landsberg erecta. Culture conditions and media
      compositions were optimized for the development of higher number of plantlets. We
      demonstrate that the combination of the plant regulators abscisic acid and
      cytokinin in the shoot induction medium increases the formation of shoots as well
      as reduces the proliferation of abnormal tissues.

PMID- 22610630
TI  - Cryopreservation of shoot tips and meristems: an overview of contemporary
      methodologies.
AB  - Cryopreservation is the storage of viable bioresources at ultra-low temperatures
      in liquid nitrogen (LN). This chapter provides an overview of those protocols
      most commonly used to cryopreserve in vitro derived shoot tips and meristems;
      they are described generically, as sequential technical steps, including
      preparative and cryogenic treatments and the morphogenetic assessment of
      recovery. The importance of translating research-generated methods into formal
      Standard Operating Procedures (SOPs) is considered.

PMID- 22610631
TI  - Anther culture of chili pepper (Capsicum spp.).
AB  - Chili pepper (Capsicum spp.) is a very important horticultural crop around the
      world and is especially important for Mexicans because of its impact in the
      culture and the cuisine. Biotechnological tools such as tissue culture techniques
      and specifically anther culture may be applied successfully for plant breeding
      and genetic improvement in order to generate isogenic lines (100% homozygous) in
      a shorter time in comparison with the classic breeding methods. In this chapter,
      a protocol for efficient recovery of chili pepper haploid plants from in vitro
      cultured anthers is described.

PMID- 22610632
TI  - Production of interspecific hybrids in ornamental plants.
AB  - In breeding of ornamental plants, interspecific hybridization and
      polyploidization have successfully been used to produce novel cultivars with
      blended traits of both parents and to introgress useful traits of one species to
      another. Embryo rescue techniques and molecular cytogenetic methods have
      successfully been used to produce and characterize interspecific hybrids in
      various genera. In this paper, recent advances in interspecific hybridization are
      described based on the results obtained in Primula, Cosmos, and Kalanchoe with
      special references to the use of embryo culture techniques for rescuing the
      abortive hybrid embryos. The methods for production and characterization of
      interspecific hybrids are categorized into three steps, i.e., (1) pollination,
      (2) rescue culture of immature embryo, and (3) confirmation of hybridity and
      ploidy level of the plants obtained. For interspecific crosses, emasculation step
      is usually needed to avoid self-pollination even in the genera with self
      incompatibility system, such as Primula and Cosmos, since self-incompatibility is
      not always complete. Since interspecific crosses are usually hindered by various
      cross-incompatibility mechanisms, successful production of interspecific hybrids
      could be achieved only from limited crosses among those using many
      cultivars/strains of both parents, suggesting the importance of the selection of
      the compatible genotypes. Unilateral cross incompatibility is commonly observed
      in interspecific cross combinations, so reciprocal crosses should be conducted as
      an indispensable step. At the rescue culture step, addition of plant hormones,
      e.g., auxin cytokinin and gibberellin, to the culture medium at the appropriate
      concentrations is proved to be effective and necessary. The hybridity of the
      plants is efficiently confirmed at the seedling stage by DNA analysis in addition
      to the observation of morphological characters. The analysis of relative DNA
      contents by flow cytometry is an easy and rapid means to confirm hybridity and to
      estimate ploidy level and genomic combination.

PMID- 22610633
TI  - Plant tissue culture of fast-growing trees for phytoremediation research.
AB  - The ability of plants to remove pollutants from the environment is currently used
      in a simple and low-cost cleaning technology known as phytoremediation.
      Unfortunately, little is known about the metabolic pathways involved in the
      transformation of xenobiotic compounds and the ability of certain plants to
      tolerate, detoxify, and store high concentrations of heavy metals. Plant cell and
      tissue culture is considered an important tool for fundamental studies that
      provide information about the plant-contaminant relationships, help to predict
      plant responses to environmental contaminants, and improve the design of plants
      with enhanced characteristics for phytoremediation. Callus, cell suspensions,
      hairy roots, and shoot multiplication cultures are used to study the interactions
      between plants and pollutants under aseptic conditions. Many plant species have
      an inherent ability to accumulate/metabolize a variety of pollutants, but they
      normally produce little biomass. However, fast-growing trees are excellent
      candidates for phytoremediation because of their rapid growth, extensive root
      system, and high water uptake. This chapter outlines the in vitro plant
      production of both somaclonal variants and transgenic plants of Populus spp. that
      exhibit high tolerance to heavy metals.

PMID- 22610634
TI  - Removing heavy metals by in vitro cultures.
AB  - In vitro roots cultures of Typha latifolia and Scirpus americanus aquatic plants
      have the capacity to remove Pb (II), Mn (II), and Cr (III) from the culture
      medium. Both species remove Cr and Pb by an absorption process, while Mn is
      mainly adsorbed to the root surface. This chapter describes a protocol for the
      establishment of in vitro roots cultures (nontransformed) from T. latifolia and
      S. americanus, and the procedure for the uptake analysis of Pb (II), Mn (II), and
      Cr (III) by roots.

PMID- 22610635
TI  - Establishment of a sanguinarine-producing cell suspension culture of Argemone
      mexicana L (Papaveraceae): induction of alkaloid accumulation.
AB  - A protocol for the induction of a cell suspension culture of Argemone mexicana is
      described. This suspension has been kept for over 3 years producing sanguinarine,
      a benzophenanthridine-type alkaloid. Sanguinarine levels can be increased by
      exposing these cultures to yeast or fungal elicitation.

PMID- 22610636
TI  - Epigenetics, the role of DNA methylation in tree development.
AB  - During development of multicellular organisms, cells become differentiated by
      modulating different programs of gene expression. Cells have their own epigenetic
      signature which reflects genotype, developmental history, and environmental
      influences, and it is ultimately reflected in the phenotype of the cells and the
      organism. However, in normal development or disease situations, such as
      adaptation to climate change or during in vitro culture, some cells undergo major
      epigenetic reprogramming involving the removal of epigenetic marks in the nuclei
      followed by the establishment of a different new set of marks. Compared with
      animal cells, biotech-mediated achievements are reduced in plants despite the
      presence of cell polypotency. In forestry, any sustainable developments using
      biotech tools remain restricted to the lab, without progressing to the field for
      application. Such barriers in the translation between development and
      implementation need to be addressed by organizations that have the power to
      integrate these two fields. However, a lack of understanding of gene regulation
      is also to blame for this barrier. In recent years, great progress has been made
      in unraveling the control of gene expression. These advances are discussed in
      this chapter, including the possibility of applying this knowledge in forestry
      practice.

PMID- 22610637
TI  - The potential roles of microRNAs in molecular breeding.
AB  - microRNAs (miRNAs), a class of small, endogenous, noncoding RNAs, are uncovered
      to play greatly expanded roles in a variety of plant developmental processes by
      gene silencing through inhibiting translation or promoting the degradation of
      target mRNAs. In virtue of their ability to inactivate either specific genes or
      entire gene families, artificial miRNAs function as dominant suppressors of gene
      activity when brought into a plant. Moreover, artificial target mimics are
      applied for the reduction of specific miRNA activity. Consequently, miRNA-based
      manipulations have emerged as promising new approaches for the improvement of
      crop plants. This action includes the development of breeding strategies and the
      genetic modification of agronomic traits. Herein, we describe the current miRNA
      based plant engineering approaches, and their advantages and challenges are also
      stated.

PMID- 22610638
TI  - Determination of histone methylation in mono- and dicotyledonous plants.
AB  - Epigenetics includes DNA methylation and histones posttranslational modifications
      such as methylation, acetylation, phosphorylation among others. One of the most
      abundant modifications in histone tail is the methylation. It has been found that
      the methylation pattern in the histone H3 may provide understanding of the
      process involved in cell differentiation, adaptation, and evolution in plants. In
      this work, we detail a method for isolation of nuclear proteins from small amount
      of sample to identify global changes in different lysines of the histone H3 tail
      by using immunodetection.

PMID- 22610639
TI  - Basic procedures for epigenetic analysis in plant cell and tissue culture.
AB  - In vitro culture is one of the most studied techniques, and it is used to study
      many developmental processes, especially in forestry species, because of growth
      timing and easy manipulation. Epigenetics has been shown as an important
      influence on many research analyses such as cancer in mammals and developmental
      processes in plants such as flowering, but regarding in vitro culture, techniques
      to study DNA methylation or chromatin modifications were mainly limited to
      identify somaclonal variation of the micropropagated material. Because in vitro
      culture is not only a way to generate plant material but also a bunch of
      differentially induced developmental processes, an approach of techniques and
      some research carried out to study the different changes regarding DNA
      methylation and chromatin and translational modifications that take place during
      these processes is reviewed.

PMID- 22610640
TI  - Plant tissue culture and molecular markers.
AB  - Tissue culture can be used to propagate elite material or to generate new
      variability by employing somaclonal variation. Genetic stability of the process
      must be evaluated analyzing DNA profiles by the use of molecular markers. Several
      techniques have been reported for the screening of genetic variation on tissue
      culture derived material; however, a highly informative and good relation among
      the time-cost-information is obtained using Amplified Fragment Length
      Polymorphism (AFLP) in automatic sequencer. This technique involves a double
      digestion of DNA with restriction enzymes, ligation of adapters at both
      extremities of the restriction fragments, and finally, selective polymerase chain
      reaction (PCR) amplification of the fragments. A semiautomatic process for the
      analysis could be used, but several considerations must be taken into account
      before such a use.

PMID- 22610641
TI  - Biolistic- and Agrobacterium-mediated transformation protocols for wheat.
AB  - After rice, wheat is considered to be the most important world food crop, and the
      demand for high-quality wheat flour is increasing. Although there are no GM
      varieties currently grown, wheat is an important target for biotechnology, and we
      anticipate that GM wheat will be commercially available in 10-15 years. In this
      chapter, we summarize the main features and challenges of wheat transformation
      and then describe detailed protocols for the production of transgenic wheat
      plants both by biolistic and Agrobacterium-mediated DNA-delivery. Although these
      methods are used mainly for bread wheat (Triticum aestivum L.), they can also be
      successfully applied, with slight modifications, to tetraploid durum wheat (T.
      turgidum L. var. durum). The appropriate size and developmental stage of explants
      (immature embryo-derived scutella), the conditions to produce embryogenic callus
      tissues, and the methods to regenerate transgenic plants under increasing
      selection pressure are provided in the protocol. To illustrate the application of
      herbicide selection system, we have chosen to describe the use of the plasmid
      pAHC25 for biolistic transformation, while for Agrobacterium-mediated
      transformation the binary vector pAL156 (incorporating both the bar gene and the
      uidA gene) has been chosen. Beside the step-by-step methodology for obtaining
      stably transformed and normal fertile plants, procedures for screening and
      testing transgenic wheat plants are also discussed.

PMID- 22610642
TI  - Improved genetic transformation of cork oak (Quercus suber L.).
AB  - An Agrobacterium-mediated transformation system for selected mature Quercus suber
      L. trees has been established. Leaf-derived somatic embryos in an early stage of
      development are inoculated with an AGL1 strain harboring a kanamycin-selectable
      plasmid carrying the gene of interest. The transformed embryos are induced to
      germinate and the plantlets transferred to soil. This protocol, from adult cork
      oak to transformed plantlet, can be completed in about one and a half years.
      Transformation efficiencies (i.e., percentage of inoculated explants that yield
      independent transgenic embryogenic lines) vary depending on the cork oak
      genotype, reaching up to 43%.

PMID- 22610643
TI  - Organelle transformation.
AB  - The source of genetic information in a plant cell is contained in nucleus,
      plastids, and mitochondria. Organelle transformation is getting a lot of
      attention nowadays because of its superior performance over the conventional and
      most commonly used nuclear transformation for obtaining transgenic lines. Absence
      of gene silencing, strong predictable transgene expression, and its application
      in molecular pharming, both in pharmaceutical and nutraceuticals, are some of
      many advantages. Other important benefits of utilizing this technology include
      the absence of transgene flow, as organelles are maternally inherited. This may
      increase the acceptability of organelle transformation technology in the
      development of transgenic crops in a wider scale all over the globe. As the need
      for crop productivity and therapeutic compounds increases, organelle
      transformation may be able to bridge the gap, thereby having a definite promise
      for the future.

PMID- 22610644
TI  - Appendix A: The components of the culture media.
AB  - The success in the technology and application of plant tissue culture is greatly
      influenced by the nature of the culture medium used. A better understanding of
      the nutritional requirements of cultured cells and tissues can help to choose the
      most appropriate culture medium for the explant used. It is also important to pay
      attention to a number of inaccuracies and errors which have appeared in several
      widely used plant tissue culture basal medium formulations.

PMID- 22610645
TI  - Appendix B: Plant biotechnology and tissue culture resources in the internet.
AB  - This appendix compiles a list of useful Internet sites for cell culture
      scientists. A total of more than 100 sites have been selected, based on the
      quality of the information offered in them, as well as on their users'
      friendliness. We anticipate that some of these sites will be included among the
      reader's favorites (if they are not already).

PMID- 22610646
TI  - Rare oncogenic mutations of predictive markers for targeted therapy in triple
      negative breast cancer.
AB  - Women with triple-negative breast cancer (TNBC) do not benefit from endocrine
      therapy or trastuzumab. Chemotherapy is the only systemic therapy currently
      available. To reduce the elevated risk of disease progression in these patients,
      better treatment options are needed, which are less toxic and more targeted to
      this patient population. We performed a comprehensive analysis of potential
      targetable genetic aberrations affecting the receptor tyrosine kinase/RAS/MAPK
      pathway, which are observed at higher frequencies in adenocarcinomas of other
      organs. Sixty-five individual TNBCs were studied by sequence analysis for HER2
      (exon 18-23), EGFR (exon 18-21), KRAS (exon 2), and BRAF (exon 15) mutations. In
      addition, a tissue microarray was constructed to screen for EGFR gene copy gain
      and EML4-ALK fusion by FISH. Triple-negative status was confirmed by
      immunohistochemistry and FISH on tissue microarray sections. EGFR and CK5/6
      immunohistochemical analyses were performed for identification of the basal-like
      phenotype. In addition, mutation analysis of TP53 (exon 5-8) was included.
      Sequence analysis revealed HER2 gene mutation in only one patient (heterozygous
      missense mutation in exon 19: p.L755S). No mutations were found in EGFR, KRAS,
      and BRAF. High polysomy of EGFR was detected in 5 of the 62 informative cases by
      FISH. True EGFR gene amplification accompanied by strong membranous EGFR protein
      expression was observed in only one case. No rearrangement of the ALK gene was
      detected. Basal-like phenotype was identified in 38 of the 65 TNBCs (58.5 %).
      TP53 gene mutation was found in 36/63 (57.1 %) tumors. We conclude that
      targetable genetic aberrations in the receptor tyrosine kinase/RAS/MAPK pathway
      occur rarely in TNBC.

PMID- 22610647
TI  - Physiochemical and biochemical factors influencing the pharmacokinetics of
      antibody therapeutics.
AB  - Monoclonal antibodies are increasingly being developed to treat multiple disease
      areas, including those related to oncology, immunology, neurology, and
      ophthalmology. There are multiple factors, such as charge, size, neonatal Fc
      receptor (FcRn) binding affinity, target affinity and biology, immunoglobulin G
      (IgG) subclass, degree and type of glycosylation, injection route, and injection
      site, that could affect the pharmacokinetics (PK) of these large macromolecular
      therapeutics, which in turn could have ramifications on their efficacy and
      safety. This minireview examines how characteristics of the antibodies could be
      altered to change their PK profiles. For example, it was observed that a net
      charge modification of at least a 1-unit shift in isoelectric point altered
      antibody clearance. Antibodies with enhanced affinity for FcRn at pH 6.0 display
      longer serum half-lives and slower clearances than wild type. Antibody fragments
      have different clearance rates and tissue distribution profiles than full length
      antibodies. Fc glycosylation is perceived to have a minimal effect on PK while
      that of terminal high mannose remains unclear. More investigation is warranted to
      determine if injection route and/or site impacts PK. Nonetheless, a better
      understanding of the effects of all these variations may allow for the better
      design of antibody therapeutics.

PMID- 22610648
TI  - Cloning and molecular characterization of a putative bZIP transcription factor
      VvbZIP23 from Vitis vinifera.
AB  - The proteins harboring bZIP domains comprise a large family and play key roles in
      many cellular processes, one of them being tolerance to biotic and abiotic
      stresses in plants. In the present study, we characterize a putative bZIP
      transcription factor from Vitis vinifera namely VvbZIP23. Our studies revealed
      that a GFP fusion of VvbZIP23 is localized in the nucleus showing VvbZIP23 codes
      for a nuclear localized protein. VvbZIP23 identified by in silico approaches from
      grapevine DNA databases available in the public domain NCBI is present in a
      single copy in the grapevine genome as shown by Southern blot analysis.
      Expression of VvbZIP23 is induced by a wide spectrum of abiotic stresses,
      including drought, salt, and cold. Exogenous application of signaling chemicals
      like abscisic acid, methyl viologen, salicylic acid, jasmonic acid, and ethephon
      also induced expression of VvbZIP23. This shows that VvbZIP23 is involved in
      regulating a number of stress responses in V. vinifera. The 5' proximal region of
      VvbZIP23 contains many cis-acting elements, which show induction of VvbZIP23
      expression in multiple stress responses. Transcripts of VvbZIP23 were found in
      many parts of the grapevine plant with the highest expression detected in leaves.
      Further in silico analysis shows that the open reading frame of VvbZIP23 is 822
      bp long and codes for a 273 amino acid long protein having a characteristic bZIP
      domain in its N-terminal end. Overexpression of VvbZIP23-GFP fusion protein in
      grapevine callus leads to enhanced transcript levels of genes, homologues of
      which are reported to be important in regulating many stress conditions.

PMID- 22610649
TI  - Transverse testicular ectopia: three additional cases and a review of the
      literature.
AB  - PURPOSE: Transverse testicular ectopia (TTE) is a well described, rare congenital
      abnormality of testicular descent, in which both testes migrate through one
      inguinal canal. The objective of this work was to present three cases of TTE, one
      of them with a common vas deferens. To our knowledge, a fused vas deferens has
      only been reported four times in previously published reports. METHODS: Three
      patients presented with inguinal hernia and contralateral cryptorchidism. In case
      1, the diagnosis of TTE was made preoperatively by palpating two testes in one
      hemiscrotum. The diagnosis of case 2 was made intraoperatively and was found to
      be of a rare form in which the two vasa deferentia fused in the inguinal canal to
      form a common vas deferens. The diagnosis of case 3 was also done
      intraoperatively and a laparoscopy was performed to document the anatomy of TTE
      and to rule out the presence of Mullerian duct remnants. We also performed a
      literature search for other reports of TTE. RESULTS: The three cases were
      operated with trans-septal orchidopexy. In addition, laparoscopy was performed in
      case 3 to clarify the anatomy. Biopsy revealed normal testicular tissue from both
      testes in the first two patients. Follow-up with ultrasound, 6 months after
      operation showed normal size and blood flow of both testes. CONCLUSION:
      Transverse testicular ectopia should be suspected in a boy with an inguinal
      hernia and contralateral non palpable testis. Trans-septal orchidopexy is
      recommended when vasa deferentia are fused. Laparoscopy is useful to document the
      anatomy and to rule out the presence of Mullerian remnants.

PMID- 22610651
TI  - KCNQ1OT1 hypomethylation: a novel disguised genetic predisposition in sporadic
      pediatric adrenocortical tumors?
AB  - Pediatric adrenal tumors, other than neuroblastoma, are rare and can be
      associated with a genetic predisposition. In this report we describe two patients
      with an isolated and apparently sporadic adrenocortical tumor; one girl with a
      carcinoma, the other girl with an adenoma. In both patients genetic screening
      revealed hypomethylation of the KCNQ1OT1 gene, well-known for its association
      with the Beckwith-Wiedemann syndrome. This represents a likely novel genetic
      predisposition in patients with adrenocortical tumors without clear phenotypic
      features of the Beckwith-Wiedemann syndrome.

PMID- 22610652
TI  - Personal genomic testing as part of the complete breast cancer risk assessment: a
      case report.
AB  - Patient access and utilization of personal genomic testing is becoming
      increasingly common. We present a case of a patient's personal genomic screening
      results leading to early detection of infiltrating breast ductal cell carcinoma
      via MRI scan. This case exemplifies the successful integration of personal
      genomic testing into the primary care setting, with the guidance and support of
      genetic counseling services. We discuss the scientific basis of the patient's
      genome scan results and risk assessment, and how this informed her decision
      making and subsequent screening. We also expound upon the role of personal
      genomic testing as compared to other screening tests in the complete breast
      cancer risk assessment.

PMID- 22610653
TI  - The laboratory-clinician team: a professional call to action to improve
      communication and collaboration for optimal patient care in chromosomal
      microarray testing.
AB  - The International Standards for Cytogenomic Arrays (ISCA) Consortium is a
      worldwide collaborative effort dedicated to optimizing patient care by improving
      the quality of chromosomal microarray testing. The primary effort of the ISCA
      Consortium has been the development of a database of copy number variants (CNVs)
      identified during the course of clinical microarray testing. This database is a
      powerful resource for clinicians, laboratories, and researchers, and can be
      utilized for a variety of applications, such as facilitating standardized
      interpretations of certain CNVs across laboratories or providing phenotypic
      information for counseling purposes when published data is sparse. A recognized
      limitation to the clinical utility of this database, however, is the quality of
      clinical information available for each patient. Clinical genetic counselors are
      uniquely suited to facilitate the communication of this information to the
      laboratory by virtue of their existing clinical responsibilities, case management
      skills, and appreciation of the evolving nature of scientific knowledge. We
      intend to highlight the critical role that genetic counselors play in ensuring
      optimal patient care through contributing to the clinical utility of the ISCA
      Consortium's database, as well as the quality of individual patient microarray
      reports provided by contributing laboratories. Current tools, paper and
      electronic forms, created to maximize this collaboration are shared. In addition
      to making a professional commitment to providing complete clinical information,
      genetic counselors are invited to become ISCA members and to become involved in
      the discussions and initiatives within the Consortium.

PMID- 22610654
TI  - Chemical modification of graphene characterized by Raman and transport
      experiments.
AB  - A chemical approach to modify the electronic transport of graphene is
      investigated by detailed transport and Raman spectroscopy measurements on Hall
      bar shaped samples. The functionalization of graphene with nitrobenzene diazonium
      ions results in a strong p-doping of the graphene samples and only slightly lower
      mobilities. Comparing Raman and transport data taken after each functionalization
      step allowed the conclusion that two preferential reactions take place on the
      graphene surface. In the beginning a few nitrobenzene molecules are directly
      attached to the graphene atoms creating defects. Afterwards these act as seeds
      for a polymer like growth not directly connected to the graphene atoms. The
      effects of solvents were excluded by thorough control measurements.

PMID- 22610656
TI  - Shared pollinators and pollen transfer dynamics in two hybridizing species,
      Rhinanthus minor and R. angustifolius.
AB  - Gene flow between hybridizing plant species depends strongly on pollinator
      behaviour, which affects pollen transfer among floral types and reproductive
      isolation. We examined bumblebee behaviour and pollen transfer between two
      hybridizing Rhinanthus species that are very similar in ecology and floral
      traits. The two species, Rhinanthus minor and R. angustifolius, shared similar
      pollinator guilds and assemblages, but pollinator recruitment and flower
      visitation rates were higher in R. angustifolius sites, probably because of its
      higher reward levels and better visibility. When presented with Rhinanthus
      flowers, bumblebees that previously foraged on R. angustifolius were less prone
      to visit R. minor inflorescences, while R. minor foragers accepted both species
      in similar proportions. Although Rhinanthus has been cited as a case of
      mechanical isolation resulting from interactions between bee behaviour and
      differences in stigma and anther placement, we found no support for efficient
      mechanical reproductive isolation. Bumblebees that foraged on R. minor flowers
      carried more pollen, but pollen placement on their bodies was similar to that of
      bees that visited R. angustifolius, and cross-specific stigmatic pollen
      deposition was similar in both directions. However, the asymmetry in pollinator
      handling time between the two species, due to dissimilar pollen rewards, may have
      lowered relative heterospecific pollen receipt on R. angustifolius, suggesting
      that net gene flow resulting from pollen transfer dynamics is more likely towards
      R. minor, although this effect remains weak and will be most likely
      counterbalanced by context-based labile pollinator preference.

PMID- 22610657
TI  - Do we really understand what constitutes an acupuncture point?: commentary on a
      paper by Molsberger et al. (this issue).

PMID- 22610655
TI  - High-throughput analysis of peptide-binding modules.
AB  - Modular protein interaction domains (PIDs) that recognize linear peptide motifs
      are found in hundreds of proteins within the human genome. Some PIDs such as SH2,
      14-3-3, Chromo, and Bromo domains serve to recognize posttranslational
      modification (PTM) of amino acids (such as phosphorylation, acetylation,
      methylation, etc.) and translate these into discrete cellular responses. Other
      modules such as SH3 and PSD-95/Discs-large/ZO-1 (PDZ) domains recognize linear
      peptide epitopes and serve to organize protein complexes based on localization
      and regions of elevated concentration. In both cases, the ability to nucleate
      specific signaling complexes is in large part dependent on the selectivity of a
      given protein module for its cognate peptide ligand. High-throughput (HTP)
      analysis of peptide-binding domains by peptide or protein arrays, phage display,
      mass spectrometry, or other HTP techniques provides new insight into the
      potential protein-protein interactions prescribed by individual or even whole
      families of modules. Systems level analyses have also promoted a deeper
      understanding of the underlying principles that govern selective protein-protein
      interactions and how selectivity evolves. Lastly, there is a growing appreciation
      for the limitations and potential pitfalls associated with HTP analysis of
      protein-peptide interactomes. This review will examine some of the common
      approaches utilized for large-scale studies of PIDs and suggest a set of
      standards for the analysis and validation of datasets from large-scale studies of
      peptide-binding modules. We will also highlight how data from large-scale studies
      of modular interaction domain families can provide insight into systems level
      properties such as the linguistics of selective interactions.

PMID- 22610658
TI  - Impact of disease severity on healthcare costs in patients with chronic hepatitis
      C (CHC) virus infection.
AB  - Hepatitis C virus (HCV) infection increases total healthcare costs but the effect
      of the severity of liver disease associated with chronic hepatitis C (CHC) on
      healthcare costs has not been well studied. We analyzed the demographics,
      healthcare utilization, and healthcare costs of CHC patients in a large U.S.
      private insurance database (January, 2002 to August, 2010), with at least 1 year
      of baseline enrollment and 30 days of continuous follow-up. Patients were
      stratified by liver disease severity: noncirrhotic liver disease (NCD),
      compensated cirrhosis (CC), and endstage liver disease (ESLD), as defined by the
      International Classification of Diseases, 9th Revision, Clinical Modification
      (ICD-9) codes. Mean all-cause and HCV-related healthcare costs per-patient-per
      month (PPPM) during follow-up (mean 634 days) are reported in 2010 U.S.$ from the
      payer's perspective. A total of 53,796 patients with CHC were included (NCD:
      41,858 [78%]; CC: 3,718 [7%]; and ESLD: 8,220 [15%]). Mean all-cause PPPM
      healthcare costs were 32% and 247% higher for patients with CC and ESLD compared
      to those with NCD ($1,870 and $4,931 versus $1,420; P < 0.001) and were
      independent of age or comorbid conditions. Pharmacy, ambulatory, and inpatient
      care collectively accounted for 90% of NCD costs and 93% of CC and ESLD costs.
      The largest cost components were inpatient costs for those with ESLD (56%) and
      ambulatory costs for those with CC and NCD (37% and 36%, respectively). Overall,
      56% of costs were HCV-related and this proportion increased with severity (46%,
      57%, and 71% for patients with NCD, CC, and ESLD, respectively). CONCLUSION: The
      direct healthcare costs associated with CHC are high, increase in association
      with the progression of liver disease, and are highest in those with ESLD.

PMID- 22610659
TI  - Nanoporous peptide particles for encapsulating and releasing neurotrophic factors
      in an animal model of neurodegeneration.
AB  - Neurotrophin-BDNF can be effectively encapsulated in nanoporous poly(L-glutamic
      acid) particles prepared via mesoporous silica templating. The loaded BDNF can be
      released in a sustained manner with retained biological activity. Animal
      experiments demonstrate the released BDNF can efficiently rescue the auditory
      neurons (as indicated by the arrows) in the cochlea of guinea pigs with
      sensorineural hearing loss.

PMID- 22610660
TI  - Development of vascular tissue and stress inducible hybrid-synthetic promoters
      through dof-1 motifs rearrangement.
AB  - A Caulimovirus-based hybrid-promoter, EFCFS, was derived by fusing the distal
      region (-227 to -54, FUAS) of Figwort mosaic virus full-length transcript
      promoter (F20) with the core promoter (-151 to +12, FS3CP) domain of Figwort
      mosaic virus sub-genomic transcript promoter (FS3). The hybrid-promoter (EFCFS)
      showed enhanced activity compared to the CaMV35S, F20 and FS3 promoters; while it
      showed equivalent activity with that of the CAMV35S(2) promoter in both transient
      protoplast (Nicotiana tabacum cv. Xanthi Brad) and transgenic plants (Nicotiana
      tabacum; Samsun NN). Further, we have engineered the EFCFS promoter sequence by
      inserting additional copies of the stress-inducible 'AAAG' cis-motif (Dof-1) to
      generate a set of three hybrid-synthetic promoters namely; EFCFS-HS-1, EFCFS-HS-2
      and EFCFS-HS-3-containing 10, 11 and 13 'AAAG' motif, respectively. Transgenic
      plants expressing these hybrid synthetic promoters coupled to the GUS reporter
      were developed and their transcriptional activities were compared with F20, FS3,
      35S and 35S(2) promoters, respectively. The relative levels of uidA-mRNA
      accumulation in transgenic plants driven by above promoters individually were
      compared by qRT-PCR. Localization of GUS reporter activity in plant tissue was
      assayed by histochemical approach. CLSM-based study revealed that hybrid
      synthetic promoters namely; EFCFS-HS-1, EFCFS-HS-2 and EFCFS-HS-3 showed enhanced
      activity in vascular tissue compared to the CaMV35S promoter. In the presence of
      abiotic stress elicitors, salicylic acid and jasmonic acid, the EFCFS-HS-1
      promoters showed enhanced activity compared to the 35S promoter. Newly derived
      hybrid-synthetic promoter/s with enhanced activity and stress inducibility could
      become efficient tools for advancement of plant biotechnology.

PMID- 22610661
TI  - Structural aspects and chaperone activity of human HspB3: role of the "C-terminal
      extension".
AB  - HspB3, an as yet uncharacterized sHsp, is present in muscle, brain, heart, and in
      fetal tissues. A point mutation correlates with the development of axonal motor
      neuropathy. We purified recombinant human HspB3. Circular dichroism studies
      indicate that it exhibits beta-sheet structure. Gel filtration and sedimentation
      velocity experiments show that HspB3 exhibits polydisperse populations with
      predominantly trimeric species. HspB3 exhibits molecular chaperone-like activity
      in preventing the heat-induced aggregation of alcohol dehydrogenase (ADH). It
      exhibits moderate chaperone-like activity towards heat-induced aggregation of
      citrate synthase. However, it does not prevent the DTT-induced aggregation of
      insulin, indicating that it exhibits target protein-dependent molecular chaperone
      like activity. Unlike other sHsps, it has a very short C-terminal extension.
      Fusion of the C-terminal extension of alphaB-crystallin results in altered
      tertiary and quaternary structure, and increase in polydispersity of the chimeric
      protein, HspB3alphaB-CT. The chimeric protein shows comparable chaperone-like
      activity towards heat-induced aggregation of ADH and citrate synthase. However,
      it shows enhanced activity towards DTT-induced aggregation of insulin. Our study,
      for the first time, provides the structural and chaperone functional
      characterization of HspB3 and also sheds light on the role of the C-terminal
      extension of sHsps.

PMID- 22610662
TI  - Oxidative stress in patients with obstructive sleep apnea syndrome.
AB  - PURPOSE: We aimed to investigate whether systemic oxidative stress is increased
      in patients with obstructive sleep apnea syndrome (OSAS). METHODS: A total of 18
      patients with severe OSAS and 13 controls were included in the study. Inclusion
      criteria for OSAS patients were: snoring and apnea-hypopnea index (AHI) of >30 in
      full polysomnography, no previous treatment for OSAS, non-smoking status, and a
      medical history of being free of comorbidities known to increase oxidative
      stress. Controls were recruited among subjects assessed for snoring in the Sleep
      Laboratory Department if they had AHI<5. At baseline, patients were evaluated by
      the Epworth Sleepiness Scale and underwent spirometry, echocardiography, and full
      polysomnographic study. Blood samples were collected for evaluation of oxidative
      stress biomarkers [protein carbonyls, reduced (GSH) and oxidized (GSSG)
      glutathione, 8-isoprostane, thiobarbituric acid-reactive substances (TBARS),
      catalase activity, Cu-Zn superoxide dysmutase (SOD), total antioxidant capacity
      (TAC)] before and on the morning following polysomnography. RESULTS: The
      overnight (morning-night) change (%) of GSH/GSSG ratio and GSH was significantly
      different between OSAS and controls (p = 0.03 and p = 0.048, respectively).
      Plasma protein carbonyls, erythrocyte catalase activity, 8-isoprostane, SOD,
      TBARS, and TAC plasma values were not different between OSAS and controls (p >
      0.05). No significant correlation was found between changes in the levels of
      biomarkers and AHI, arousal, or desaturation index. CONCLUSION: The present
      prospective investigation in a population free of comorbidities or factors which
      may increase systemic oxidative stress provides evidence that obstructive sleep
      apnea per se might be associated with increased oxidative burden possibly via
      GSH/GSSG pathway.

PMID- 22610663
TI  - Identification of group A streptococcal emm types commonly associated with
      invasive infections and antimicrobial resistance by the use of multiplex PCR and
      high-resolution melting analysis.
AB  - M/emm typing, based either on serotyping of the M protein or on sequencing of the
      emm gene, is a major tool for epidemiological studies of group A streptococci
      (GAS). In order to simplify M/emm typing, we designed two multiplex polymerase
      chain reaction (PCR) formats capable of identifying the most frequent GAS M/emm
      types involved in invasive infections and antimicrobial resistance. A heptaplex
      PCR procedure was first developed in a conventional format coupled with gel
      electrophoresis to identify emm types 1, 3, 4, 6, 12, 28, and 89, based on the
      size of the amplification products. The other method, designed to identify the
      same seven emm types, together with emm11, was based on a real-time PCR format
      coupled with high-resolution melting (HRM) analysis, allowing the rapid typing of
      large strain collections.

PMID- 22610665
TI  - A known and a novel mutation in the glycine decarboxylase gene in a newborn with
      classic nonketotic hyperglycinemia.
AB  - A term neonate displayed typical features of nonketotic hyperglycinemia (NKH).
      Conventional magnetic resonance imaging showed corpus callosum hypoplasia and
      increased signal intensity of the white matter. Magnetic resonance proton
      spectroscopy revealed high cerebral glycine levels. The liquor/plasma glycine
      ratio was increased. Genetic testing detected a known and a novel mutation in the
      glycine decarboxylase gene, leading to the classic form of glycine
      encephalopathy. Prenatal genetic testing in the subsequent pregnancy showed that
      this fetus was not affected. As features of neonatal NKH may not be very
      specific, recognition of the disease may be difficult. An overview of clinical,
      electroencephalography, and neuroimaging findings is given in this article.

PMID- 22610664
TI  - A novel GJC2 mutation associated with hypomyelination and Mullerian agenesis
      syndrome: coincidence or a new entity?
AB  - In recent years, several new white matter diseases have been identified based on
      magnetic resonance imaging and clinical findings. For most newly defined
      disorders the genetic basis has been identified. However, there is still a large
      group of patients without a specific diagnosis. Hypomyelinating leukodystrophies
      are the largest group among them. In some disorders characterized by
      hypomyelination only central nervous system involvement is observed, but in some
      disorders involvement of other organs is observed as well, such as eyes or teeth.
      Pelizaeus-Merzbacher-like disease (PMLD) is an autosomal recessive
      hypomyelinating disorder of the central nervous system characterized by
      nystagmus, ataxia, and progressive spasticity. The disease is caused by mutations
      in GJC2, the gene that encodes the gap junction protein connexin 47. Here we
      describe hypomyelination and Mullerian agenesis syndrome in a girl who is
      homozygous for a novel mutation in the GJC2 gene. It is an open question whether
      this is an association by chance or a feature of PMLD not previously noted.

PMID- 22610666
TI  - Isolated cystic lesion of the callosal genu after traumatic brain injury.
AB  - We report the case of a 17-month-old infant who developed an isolated cystic
      lesion of the callosal genu as a unique lesion of traumatic axonal injury (TAI).
      Although one of the most common sites of TAI is the corpus callosum, there have
      been no reports describing the lesion seen in our patient. Brain computed
      tomography findings were normal on the day of the traffic accident. After 3
      months, brain magnetic resonance imaging showed an isolated cystic lesion of the
      callosal genu that had the appearance of a cystic cavity. This lesion decreased
      in size 16 months later. The neuroimaging findings of this patient suggest that
      an isolated cystic lesion of the callosal genu could appear as a unique form of
      TAI in infants after traumatic brain injury (TBI), but it is nevertheless
      important to attend to such lesions in children with TBI.

PMID- 22610667
TI  - Body mass index and lung cancer risk: results from the ICARE study, a large,
      population-based case-control study.
AB  - BACKGROUND: The association between body mass index (BMI) and lung cancer is
      still disputed because of possible residual confounding by smoking and
      preclinical weight loss in case-control studies. We examined this association
      using data from the multicenter ICARE study in France, a large, population-based
      case-control study. METHODS: A total of 2,625 incident lung cancer cases and
      3,381 controls were included. Weight was collected at interview, 2 years before
      the interview, and at age 30. Lifetime smoking exposure was calculated using the
      comprehensive smoking index (CSI). Adjusted odds ratios (aORs) and 95 %
      confidence intervals were estimated by unconditional logistic regression and
      controlled for age, area, education, CSI, occupational exposure, previous chronic
      bronchitis, and parental history of lung cancer. We also examined the role of
      weight change. Analyses were stratified by smoking status and sex. RESULTS: When
      compared with that of men with normal BMI 2 years before the interview, lung
      cancer aORs (95 % CI) among men with BMIs of <18.5, 25-29.9, 30-32.4, and >=32.5
      kg/m(2) were 2.7 (95 % CI 1.2-6.2), 0.9 (95 % CI 0.7-1.1), 0.8 (95 % CI 0.6-1.1),
      and 0.8 (95 % CI 0.6-1.0), respectively (p(trend) = 0.02). Results were more
      pronounced among current smokers and were similar in men and women. Weight gain
      over time was associated with a significant decreased risk of lung cancer.
      CONCLUSIONS: We found an inverse dose-dependent association between lung cancer
      risk and BMI 2 years prior to interview in current smokers. IMPACT STATEMENT: BMI
      might be an individual factor impacting the risk of lung cancer related to
      smoking's carcinogen-induced DNA damage.

PMID- 22610668
TI  - Contrast-enhanced sonography in the diagnosis of hepatic hemangiomas: atypical
      appearance due to the washout of microbubbles.
AB  - Contrast-enhanced sonography (CEUS) examination permits identification of
      hemangioma of the liver in most cases. This method is particularly useful when
      the ultrasound pattern is atypical on standard grayscale examination. CEUS
      appearances suggestive of hemangioma are peripheral globular enhancement,
      progression of enhancement toward the center of the nodule, and persistence of
      enhancement in the late phase. We present seven cases of hemangioma, which were
      atypical on CEUS examination due to washout during the portal and late phases,
      resulting in a hypoenhanced appearance compared with the adjacent liver
      parenchyma.

PMID- 22610669
TI  - Development and validation of a direct sandwich chemiluminescence immunoassay for
      measuring DNA adducts of benzo[a]pyrene and other polycyclic aromatic
      hydrocarbons.
AB  - We have developed and validated a sandwich chemiluminescence immunoassay (SCIA)
      which measures polycyclic aromatic hydrocarbon (PAH)-DNA adducts combining high
      throughput and adequate sensitivity, appropriate for evaluation of adduct levels
      in human population studies. Fragmented DNA is incubated with rabbit antiserum
      elicited against DNA modified with r7,t8-dihydroxy-t-9,10-epoxy-7,8,9,10
      tetrahydrobenzo[a]pyrene (BPDE) and subsequently trapped by goat anti-rabbit IgG
      bound to a solid surface. Anti-single-stranded (ss) DNA antibodies binds in a
      quantity proportional to the adduct levels and is detected by chemiluminescence.
      The BPDE-DNA SCIA has a limit of detection of 3 adducts per 10(9) nucleotides
      with 5 MUg DNA per well. We have validated the BPDE-DNA SCIA using DNA modified
      in vitro, DNA from benzo[a]pyrene (BP)-exposed cultured cells and mice. The
      levels of adduct measured by SCIA were lower (30-60%) than levels of bulky DNA
      adducts measured in the same samples by (32)P-postlabelling. The BPDE-DNA SCIA
      also detected adducts produced in vivo by PAHs other than BP. When blood DNA
      samples from maternal/infant pairs were assayed by BPDE-DNA SCIA, the adduct
      levels obtained were significantly correlated. However, there was no correlation
      between (32)P-postlabelling and SCIA values for the same samples. The SCIA can be
      extended to any DNA adduct and is expected to provide, when fully automated, a
      valuable high-throughput approach in large-scale population studies.

PMID- 22610671
TI  - 4-Hydroxyisoleucine stimulates glucose uptake by increasing surface GLUT4 level
      in skeletal muscle cells via phosphatidylinositol-3-kinase-dependent pathway.
AB  - PURPOSE: To determine the effect of 4-Hydroxyisoleucine (4-HIL), an unusual amino
      acid isolated from the seeds of Trigonella foenum-graecum, on glucose uptake and
      the translocation of glucose transporter 4 (GLUT4) to plasma membrane in skeletal
      muscle cells and to investigate the underlying mechanisms of action. METHODS: Rat
      skeletal muscle cells (L6-GLUT4myc) were treated with 4-HIL, and the effect on
      glucose uptake was determined by measuring the incorporation of radio-labeled 2
      deoxy-[(3)H]-D-glucose (2-DG) into the cell. Translocation of GLUT4myc to plasma
      membrane was measured by an antibody-coupled colorimetric assay. RESULTS: The
      prolonged exposure (16 h) of L6-GLUT4myc myotubes to 4-HIL caused a substantial
      increase in the 2-DG uptake and GLUT4 translocation to the cell surface, without
      changing the total amount of GLUT4 and GLUT1. Cycloheximide treatment reversed
      the effect of 4-HIL on GLUT4 translocation to the basal level suggesting the
      requirement of new protein synthesis. The 4-HIL-induced increase in GLUT4
      translocation was completely abolished by wortmannin, and 4-HIL significantly
      increased the basal phosphorylation of AKT (Ser-473), but did not change the mRNA
      expression of AKT, IRS-1, GLUT4, and GSK3beta. CONCLUSION: Results suggest that 4
      HIL stimulates glucose uptake in L6-GLUT4myc myotubes by enhancing translocation
      of GLUT4 to the cell surface in a PI-3-kinase/AKT-dependent mechanism.

PMID- 22610672
TI  - Constrained evolutionary algorithm for structure prediction of molecular
      crystals: methodology and applications.
AB  - Evolutionary crystal structure prediction proved to be a powerful approach for
      studying a wide range of materials. Here we present a specifically designed
      algorithm for the prediction of the structure of complex crystals consisting of
      well defined molecular units. The main feature of this new approach is that each
      unit is treated as a whole body, which drastically reduces the search space and
      improves the efficiency, but necessitates the introduction of new variation
      operators described here. To increase the diversity of the population of
      structures, the initial population and part (~20%) of the new generations are
      produced using space-group symmetry combined with random cell parameters, and
      random positions and orientations of molecular units. We illustrate the
      efficiency and reliability of this approach by a number of tests (ice, ammonia,
      carbon dioxide, methane, benzene, glycine and butane-1,4-diammonium dibromide).
      This approach easily predicts the crystal structure of methane A containing 21
      methane molecules (105 atoms) per unit cell. We demonstrate that this new
      approach also has a high potential for the study of complex inorganic crystals as
      shown on examples of a complex hydrogen storage material Mg(BH(4))(2) and
      elemental boron.

PMID- 22610670
TI  - Regulation of the exopolysaccharide from an anamorph of Cordyceps sinensis on
      dendritic cell sarcoma (DCS) cell line.
AB  - PURPOSE: Cordyceps sinensis has been regarded as a precious tonic food and herbal
      medicine in China for thousands of years. The exopolysaccharide (EPS) from an
      anamorph of Cordyceps sinensis was found to have antitumor immunomodulatory
      activity. Mature dendritic cells play a role in initiating antitumor immunity, so
      we try to investigate the effects of EPS on the murine dendritic cell line DCS.
      METHODS: Flow cytometry was used to assay the expression levels of cell surface
      molecules including major histocompatibility complex (MHC)-II, CD40, CD80, and
      CD86 of DCS cells and their ability to take up antigens. The ability of DCS cells
      to activate the proliferation of CTLL-2 T cells was measured by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. IL-12 and
      TNF-alpha levels were detected using ELISA. Western blotting was performed to
      estimate the levels of phosphorylated Janus kinase 2 (p-JAK2), phosphorylated
      signal transducer and activator of transcription 3 (p-STAT3), nuclear factor
      kappaB (NF-kappaB) p65 and p105. RESULTS: EPS increased the expressions of MHC
      II, CD40, CD80, and CD86 of DCS cells and up-regulated their ability to take up
      antigens. EPS also enhanced their ability to activate the proliferation of CTLL-2
      T cells. IL-12 and TNF-alpha secreted from DCS cells were up-regulated after EPS
      treatment. Furthermore, EPS significantly caused the decline of p-JAK2 and p
      STAT3, significantly increased levels of NF-kappaB p65 in the nucleus and
      decreased levels of NF-kappaB p105 in the cytoplasm. CONCLUSIONS: EPS may induce
      DCS cells to exhibit mature characteristics, and the mechanism involved is
      probably related to the inhibition of the JAK2/STAT3 signal pathway and promotion
      of the NF-kappaB signal pathway.

PMID- 22610673
TI  - Structural chemistry of A2MX4 compounds (X = O, F) with isolated tetrahedral
      anions: search for the densest structure types.
AB  - The packing density of various structures is important not only for understanding
      and the prediction of high-pressure phase transitions, but also because of its
      reported correlation with thermodynamic stability. Plotting the cube root of
      formula volume against the cation radii (R) for nine morphotropic series with
      isolated tetrahedral anions, A(2)MO(4) (M = Si, Ge, S, Se, Cr, Mn, Mo, W) and
      A(2)BeF(4), permits the comparison of packing densities for 13 structure types
      (about 80 individual compounds and several solid solutions) stable at (or near)
      ambient temperature. The spinel type is the densest. The next densest types are
      those of K(2)MoO(4), Tl(2)CrO(4), beta-Ca(2)SiO(4), beta-K(2)SO(4), Ag(2)CrO(4)
      and Sr(2)GeO(4). In three series (M = Ge, Mo, W) the densest type comes with
      somewhat intermediate values of R, and not the largest, in contrast to the
      classical homology rule. Another contradiction with traditional views is that
      some of the densest phases have abnormally low overall binding energies. The
      correlation between packing density and coordination number (CN) is better when
      CN of A counts entire MX(4) groups rather than individual X atoms; many, but not
      all, A(2)MX(4) structures have binary A(2)M analogues (of course, A and M are not
      necessarily the same in these structure types). The most frequent arrangement of
      A around M is of the Ni(2)In type: a (distorted) pentacapped trigonal prism.

PMID- 22610674
TI  - Helical screw type magnetic structure of the multiferroic CaMn7O12 with low Cu
      doping.
AB  - The modulated crystal structure and modulated magnetic ordering of the
      multiferroic CaCu(x)Mn(7-x)O(12) is studied by analysing neutron and synchrotron
      radiation (SR) powder diffraction data with a model based on the magnetic
      superspace group R31'(00gamma)ts. Both atomic position modulations and magnetic
      modulations are described with the modulation vector (0, 0, q). The magnetic
      ordering is a screw-type circular helix where the magnetic moments are
      perpendicular to the c direction. The temperature dependence of the modulation
      vector length and the ordered magnetic moments of Mn(3+) and Mn(4+) ions is given
      between T = 50 K and the Neel temperature T(N) is approximately equal to 90 K.
      The atomic position modulation length L(p) and the magnetic modulation length
      L(m) fulfil the relation L(m) = 2L(p) at all temperatures between 50 K and T(N).

PMID- 22610675
TI  - Structure of (Ga2O3)2(ZnO)13 and a unified description of the homologous series
      (Ga2O3)2(ZnO)(2n + 1).
AB  - The structure of (Ga(2)O(3))(2)(ZnO)(13) has been determined by a single-crystal
      X-ray diffraction technique. In the monoclinic structure of the space group C2/m
      with cell parameters a = 19.66 (4), b = 3.2487 (5), c = 27.31 (2) A, and beta =
      105.9 (1) degrees , a unit cell is constructed by combining the halves of the
      unit cell of Ga(2)O(3)(ZnO)(6) and Ga(2)O(3)(ZnO)(7) in the homologous series
      Ga(2)O(3)(ZnO)(m). The homologous series (Ga(2)O(3))(2)(ZnO)(2n + 1) is derived
      and a unified description for structures in the series is presented using the
      (3+1)-dimensional superspace formalism. The phases are treated as compositely
      modulated structures consisting of two subsystems. One is constructed by metal
      ions and another is by O ions. In the (3 + 1)-dimensional model, displacive
      modulations of ions are described by the asymmetric zigzag function with large
      amplitudes, which was replaced by a combination of the sawtooth function in
      refinements. Similarities and differences between the two homologous series
      (Ga(2)O(3))(2)(ZnO)(2n + 1) and Ga(2)O(3)(ZnO)(m) are clarified in (3 + 1)
      dimensional superspace. The validity of the (3 + 1)-dimensional model is
      confirmed by the refinements of (Ga(2)O(3))(2)(ZnO)(13), while a few complex
      phenomena in the real structure are taken into account by modifying the model.

PMID- 22610676
TI  - Parallel stacking interactions in square-planar transition-metal complexes
      containing fused chelate and C6-aromatic rings.
AB  - Stacking interactions in the crystal structures of square-planar transition metal
      complexes from the Cambridge Structural Database with five- and six-membered
      chelate rings fused with C(6-arom) rings (arom = aromatic) were analyzed. The
      distribution of distances between the closest C(6-arom)-C(6-arom) and C(6-arom)
      chelate contacts shows that in a large fraction of the intermolecular
      interactions the C(6-arom) ring of one molecule is closer to the chelate than to
      the C(6-arom) ring of the other molecule. These results indicate a possible
      preference of the C(6-arom) ring to form stacking contacts with the chelate
      rings. The preference is ubiquitous and does not depend on the metal type.

PMID- 22610677
TI  - Phase transition at high pressure in Cu2CO3(OH)2 related to the reduction of the
      Jahn-Teller effect.
AB  - Hydroxycarbonates with the general formula Me(2)(CO(3))(OH)(2) are widely used
      materials in industrial processes and are widespread in nature. The Cu term,
      malachite, Cu(2)CO(3)(OH)(2), is monoclinic, P2(1)/a. Substitution of Cu(2+) with
      other bivalent cations such as Mg, Zn, Fe, Cu or Ni is possible and leads to a
      different structure type, rosasite, P2(1)/a or P2(1)/b11 in the same cell setting
      as malachite. Rosasite structure is topologically similar to malachite, but the
      symmetry elements are oriented differently with respect to structural units. The
      stability of the malachite-like structure (MS) compared with the rosasite-like
      structure (RS) has been suggested to be related to the Jahn-Teller effect in
      CuO(6) coordination polyhedra. For this reason the hypothesis of the phase
      transition of malachite, Cu(2)CO(3)(OH)(2), to a rosasite structure at high
      pressure, as a result of the reduced Jahn-Teller effect, has been tested and
      confirmed by powder and single-crystal diffraction structural studies: above 6
      GPa the malachite structure is no longer stable and transforms to a RS structure.
      RS Cu(2)CO(3)(OH)(2) is 3% more dense than malachite and the bulk modulus is
      remarkably higher, 80 (2) GPa compared with 48 (4) GPa. The longer apical Cu-O
      bonds in the distorted Me1 octahedral site are progressively shortened with
      increasing pressure, revealing a decrease in the Jahn-Teller effect at high
      pressure. The transition has a first-order character, is reversible with a
      significant hysteresis, and there is no evidence of any intermediate phase
      between the two structures. We then have further evidence that in the
      Me(2)(CO(3))(OH)(2) compounds, the two main structural types, MS and RS, are
      closely related. The former structure is stabilized only when Cu is the prevalent
      cation in the octahedral sites, and it can transform directly to the RS as a
      function of thermodynamic changes.

PMID- 22610678
TI  - Effect of pressure on crystalline L- and DL-serine: revisited by a combined
      single-crystal X-ray diffraction at a laboratory source and polarized Raman
      spectroscopy study.
AB  - Information on the effect of pressure on hydrogen bonds, which could be derived
      from single-crystal X-ray diffraction at a laboratory source and polarized Raman
      spectroscopy, has been compared. L-Serine and DL-serine were selected for this
      case study. The role of hydrogen bonds in pressure-induced phase transitions in
      the first system and in the structural stability of the second one are discussed.
      Non-monotonic distortion of selected hydrogen bonds in the pressure range below
      ~1-2 GPa, a change in the compression mechanism at ~2-3 GPa, and the evidence of
      formation of bifurcated N-H...O hydrogen bonds in DL-serine at ~3-4 GPa are
      considered.

PMID- 22610679
TI  - Low-temperature phase transition in glycine-glutaric acid co-crystals studied by
      single-crystal X-ray diffraction, Raman spectroscopy and differential scanning
      calorimetry.
AB  - The occurrence of a first-order reversible phase transition in glycine-glutaric
      acid co-crystals at 220-230 K has been confirmed by three different techniques -
      single-crystal X-ray diffraction, polarized Raman spectroscopy and differential
      scanning calorimetry. The most interesting feature of this phase transition is
      that every second glutaric acid molecule changes its conformation, and this fact
      results in the space-group symmetry change from P2(1)/c to P1. The topology of
      the hydrogen-bonded motifs remains almost the same and hydrogen bonds do not
      switch to other atoms, although the hydrogen bond lengths do change and some of
      the bonds become inequivalent.

PMID- 22610680
TI  - Relation between photochromic properties and molecular structures in
      salicylideneaniline crystals.
AB  - The crystal structures of the salicylideneaniline derivatives N-salicylidene-4
      tert-butyl-aniline (1), N-3,5-di-tert-butyl-salicylidene-3-methoxyaniline (2), N
      3,5-di-tert-butyl-salicylidene-3-bromoaniline (3), N-3,5-di-tert-butyl
      salicylidene-3-chloroaniline (4), N-3,5-di-tert-butyl-salicylidene-4-bromoaniline
      (5), N-3,5-di-tert-butyl-salicylidene-aniline (6), N-3,5-di-tert-butyl
      salicylidene-4-carboxyaniline (7) and N-salicylidene-2-chloroaniline (8) were
      analyzed by X-ray diffraction analysis at ambient temperature to investigate the
      relationship between their photochromic properties and molecular structures. A
      clear correlation between photochromism and the dihedral angle of the two benzene
      rings in the salicylideneaniline derivatives was observed. Crystals with dihedral
      angles less than 20 degrees  were non-photochromic, whereas those with dihedral
      angles greater than 30 degrees  were photochromic. Crystals with dihedral angles
      between 20 and 30 degrees  could be either photochromic or non-photochromic.
      Inhibition of the pedal motion by intra- or intermolecular steric hindrance,
      however, can result in non-photochromic behaviour even if the dihedral angle is
      larger than 30 degrees .

PMID- 22610681
TI  - Voronoi-Dirichlet tesselation as a tool for investigation of polymorphism in
      molecular crystals with CwHxNyOz composition and photochromic properties.
AB  - The non-bonded interactions in five sets of polymorph substances with
      photochromic properties have been investigated within the Voronoi-Dirichlet
      approach. Twenty compounds with the general formula C(w)H(x)N(y)O(z) were
      analyzed. Among ten possible types of non-bonded interactions at least five types
      are observed in the crystal structures of compounds under discussion. For all the
      structures the majority of interactions involve H atoms, namely London forces
      (H...H and H...C) and hydrogen bonds (H...O and H...N). A conformational
      polymorph was stated to be characterized by a unique set of inter- and
      intramolecular non-bonded interactions. It was quantitatively demonstrated that
      molecules in the same conformation can pack in a different way, and, vice versa,
      the change in conformation of a molecule does not prevent a substance from
      realising the same set of intermolecular contacts. In accordance with the data
      obtained for 2,4-dinitrobenzylpyridine derivatives, only conformational
      polymorphs with an intramolecular N...N interaction between a nitro group and a
      pyridine are photochromic.

PMID- 22610682
TI  - Invariom modeling of ceftazidime pentahydrate: molecular properties from a 200
      second synchrotron microcrystal experiment.
AB  - The structure of ceftazidime pentahydrate, a third generation cephalosporin
      antibiotic, is reported. Data collection was carried out in a remarkably short
      time with synchrotron radiation and the latest detector technology, illustrating
      that single-crystal X-ray diffraction can be used as a technique for screening
      hundreds of compounds in a short amount of time. Structure refinement made use of
      invarioms, namely non-spherical scattering factors, which allow more information
      to be derived from a diffraction experiment. Properties that can be screened are
      bond-topological parameters, empirical hydrogen-bond energies, molecular dipole
      moments and electrostatic potentials.

PMID- 22610683
TI  - Exact solution of the bond-valence sum rule for a set of coordination shells.
AB  - The calculation scheme for determining the bond-valence parameters (r(0) and b)
      resulting in the exact solution of the bond-valence sum rule for a given set of
      coordination shells is presented.

PMID- 22610685
TI  - Prognosis and outcome of relapsed acute lymphoblastic leukemia: a Hong Kong
      Pediatric Hematology and Oncology Study Group report.
AB  - BACKGROUND: In 2000, the Hong Kong Pediatric Hematology Oncology Study Group
      started a new relapsed acute lymphoblastic leukemia (ALL) treatment protocol
      based on modified ALL-REZ BFM 96 protocol aiming at improving the treatment
      outcome in Chinese children. PROCEDURE: All patients in Hong Kong with first
      relapse of childhood ALL were included. Patients were stratified into four risk
      groups (S1, S2, S3, and S4) and the treatment consisted of intensive chemotherapy
      followed by allogeneic hematopoietic stem cell transplantation, if indicated.
      RESULTS: Fifty-six patients were recruited and median age at diagnosis of ALL was
      4.6 (range, 0.3-17) years. The median time from initial diagnosis to relapse was
      2.5 (range, 0.3-9.1) years and follow-up time was 2.7 (range, 0-9.9) years. Forty
      nine patients (87.5%) achieved second complete remission (CR2). CR2 rates for S1,
      S2, S3, and S4 groups were 100%, 93%, 90%, and 67%, respectively. Five-year
      overall survival (OS) was 50.5 +/- 6.9% and event-free survival (EFS) was 41.5 +/
      7.1%. There was no significant difference in survival among S1, S2, and S3
      groups but S4 patients performed significantly worse with 5-year OS and EFS of 8%
      and 0%, respectively. CONCLUSION: Children with relapsed ALL of S1-S3 risk groups
      could be successfully treated with intensified treatment protocol. The S4 high
      risk group needs more innovative approach to improve treatment outcome.

PMID- 22610686
TI  - Blood pressure control with angiotensin receptor blocker-based three-drug
      combinations: key trials.
AB  - INTRODUCTION: Most hypertensive patients only achieve blood pressure (BP) control
      with a combination of antihypertensive drugs from different classes and many
      require three or more drugs. Two three-drug, fixed-dose combinations are
      available: (1) the angiotensin receptor blocker (ARB), valsartan (VAL), the
      calcium channel blocker, amlodipine (AML), and the diuretic, hydrochlorothiazide
      (HCTZ); (2) the ARB, olmesartan medoxomil (OLM), AML, and HCTZ. METHODS: This
      article reviews two clinical studies in patients with moderate-to-severe
      hypertension, which compared the efficacy and safety of VAL/AML/HCTZ and
      OLM/AML/HCTZ with the component two-drug combinations. RESULTS: Each triple
      combination produced significantly greater reductions in seated
      systolic/diastolic BP and higher BP control rates than the two-drug combinations.
      Subgroup analyses showed that BP reductions and control rates with the three-drug
      combinations were unaffected by age, gender, race, and hypertension severity
      (VAL/AML/HCTZ and OLM/AML/HCTZ), and that efficacy was maintained for up to 52
      weeks (OLM/AML/HCTZ). OLM/AML/HCTZ and VAL/AML/HCTZ also produced significantly
      larger reductions in ambulatory systolic and diastolic BP over 24 hours, the
      daytime, and nighttime compared with two-drug combinations. Adverse events were
      mainly of mild or moderate intensity and each threedrug combination was well
      tolerated. CONCLUSION: ARB/AML/HCTZ combinations produce BP reductions and
      control rates superior to two-drug combinations and may help difficult-to-treat
      patients to achieve BP control.

PMID- 22610687
TI  - X-ray crystal structure of CMS1MS2: a high proteolytic activity cysteine
      proteinase from Carica candamarcensis.
AB  - CMS1MS2 (CC-Ib) from Carica candamarcensis (Vasconcellea cundinamarcensis) is a
      cysteine proteinase found as a single polypeptide containing 213 residues of
      22,991 Da. The enzyme was purified by three chromatographic steps, two of them
      involving cationic exchange. Crystals of CMS1MS2 complexed with E-64 were
      obtained by the hanging drop vapor-diffusion method at 291 K using ammonium
      sulfate and polyethylene glycol 4000/8000 as precipitant. The complex CMS1MS2-E
      64 crystallized in the tetragonal space group P4(1)2(1)2 with unit-cell
      parameters; a = b = 73.64, c = 118.79 A. The structure was determined by
      Molecular Replacement and refined at 1.87 A resolution to a final R factor of
      16.2 % (R (free) = 19.3 %). Based on the model, the structure of CMS1MS2 (PDB
      3IOQ) ranks as one of the least basic cysteine isoforms from C. candamarcensis,
      is structurally closer to papain, caricain, chymopapain and mexicain than to the
      other cysteine proteinases, while its activity is twice the activity of papain
      towards BAPNA substrate. Two differences, one in the S2 subsite and another in
      the S3 subsite of CMS1MS2 may contribute to the enhanced activity relative to
      papain. In addition, the model provides a structural basis for the sensitivity of
      CMS1MS2 to inhibition by cystatin, not shown by other enzymes of the group, e.g.,
      glycyl endopeptidase and CMS2MS2.

PMID- 22610689
TI  - Immigrant health around the world: evidence from the World Values Survey.
AB  - We describe the relationship between immigrant status and self-rated health
      around the world, both in raw descriptive statistics and in models controlling
      for individual characteristics. Using the World Values Survey (1981-2005), we
      analyze data from 32 different countries worldwide. We estimate four regression
      models per country. The basic model tests mean differences in self-rated health.
      Additional models add demographic and social class controls. Introduction of
      control variables (most particularly, age) changes the results dramatically. In
      the final model, net of controls, only two countries show poorer immigrant health
      and three countries show better immigrant health. The multivariate regression
      models net of controls show few differences in health status between immigrants
      and the native born. The age structure of immigrant populations is an important
      mediator of differences in health status compared to the native-born population.

PMID- 22610688
TI  - In vivo protein complex topologies: sights through a cross-linking lens.
AB  - Proteins are a remarkable class of molecules that exhibit wide diversity of
      shapes or topological features that underpin protein interactions and give rise
      to biological function. In addition to quantitation of abundance levels of
      proteins in biological systems under a variety of conditions, the field of
      proteome research has as a primary mission the assignment of function for
      proteins and if possible, illumination of factors that enable function. For many
      years, chemical cross-linking methods have been used to provide structural data
      on single purified proteins and purified protein complexes. However, these
      methods also offer the alluring possibility to extend capabilities to complex
      biological samples such as cell lysates or intact living cells where proteins may
      exhibit native topological features that do not exist in purified form. Recent
      efforts are beginning to provide glimpses of protein complexes and topologies in
      cells that suggest continued development will yield novel capabilities to view
      functional topological features of many proteins and complexes as they exist in
      cells, tissues, or other complex samples. This review will describe rationale,
      challenges, and a few success stories along the path of development of cross
      linking technologies for measurement of in vivo protein interaction topologies.

PMID- 22610690
TI  - Northwest Latinos' health promotion lifestyle profiles according to diabetes risk
      status.
AB  - A sample of 225 low income and low education, middle aged Latinos with concern
      about diabetes and living in a mid-size Idaho city volunteered for a physical
      assessment for risk status for the disease. The health promoting lifestyles of
      Latino congregants were measured using the Health Promoting Lifestyle Profile II.
      Diabetes risk was measured by clinically standard glycated hemoglobin readings.
      From no risk for the disease to full blown diabetes as determined by glycated
      hemoglobin levels, the respondents reported engaging in basically the same levels
      of physical activity, monitoring of nutrition and use of health care services
      thus evidencing no apparent understanding of the role of lifestyle in disease
      management. The findings point to the imperative of a broad, comprehensive and
      especially culturally attuned educational campaign on basic disease
      pathophysiology, the value of prevention for individual health, and the necessity
      of day-to-day self-care should diabetes be diagnosed.

PMID- 22610691
TI  - Employers' role in helping Latino workers obtain access to health care services:
      results of a community-based pilot demonstration project.
AB  - A coalition of employers in the hotel and restaurant industries collaborated with
      community-based organizations to undertake a unique demonstration project, called
      the Employed Latino Health Initiative, aimed at improving access to basic health
      care services for low-wage Latino workers in Columbus, Ohio. With grant funding
      from the Robert Wood Johnson Foundation, the project developed and tested
      protocols allowing Latino workers from participating companies to obtain basic
      health care screenings, referrals to medical providers, health education
      training, and the services of a qualified community health navigator. Data from
      the pilot project indicated high screening participation rates, extensive
      referrals to providers for follow-up care, and a substantial need for
      facilitation services by community health navigators. The project provides a
      model for how employers can potentially promote their own interests in boosting
      work productivity through facilitating expanded access to basic medical services
      among vulnerable workers, despite the absence of conventional health insurance
      coverage.

PMID- 22610692
TI  - The association between acculturation and health insurance coverage for immigrant
      children from socioeconomically disadvantaged regions of origin.
AB  - Among immigrant children whose parents have historically had lower education, the
      study explored which immigrant children were most likely to have coverage based
      on maternal region of origin. The direct and indirect relationship of
      acculturation on immigrant children's coverage was also assessed. A subsample of
      US-born children with foreign-born mothers from the Early Childhood Longitudinal
      Survey-Kindergarten Cohort was analyzed using multinomial logistic regressions (n
      = 1,686). Children whose mothers emigrated from the Caribbean or Indochina had
      greater odds of being insured compared to children whose mothers emigrated from
      Mexico. Moreover, Latin American children did not statistically differ from
      Mexican children in being uninsured. Maternal citizenship was positively
      associated with children's coverage; while living in a household with a mother
      who migrated as a child was negatively associated with private insurance. To
      increase immigrant children's coverage, Latin American and Mexican families may
      benefit from additional financial assistance, rather than cultural assistance.

PMID- 22610694
TI  - Application of adaptive DO-stat feeding control to Pichia pastoris X33 cultures
      expressing a single chain antibody fragment (scFv).
AB  - In this study, fed-batch cultures of a Pichia pastoris strain constitutively
      expressing a single chain antibody fragment (scFv) under the control of the
      glyceraldehyde-3-phosphate dehydrogenase (GAP) promoter were performed in a pilot
      50 L bioreactor. Due to the very high cell density achieved within the first 75
      h, typically between 140 and 160 g-DCW/L of dry cell weight (DCW), most of the
      scFv is produced under hard oxygen transfer limitation. To improve scFv
      productivity, a direct adaptive dissolved oxygen (DO)-stat feeding controller
      that maximizes glycerol feeding under the constraint of available oxygen transfer
      capacity was developed and applied to this process. The developed adaptive
      controller enabled to maximize glycerol feeding through the regulation of DO
      concentration between 3 and 5 % of saturation, thereby improving process
      productivity. Set-point convergence dynamics are characterized by a fast response
      upon large perturbations to DO, followed by a slower but very robust convergence
      in the vicinity of the boundary with almost imperceptible overshoot. Such control
      performance enabled operating closer to the 0 % boundary for longer periods of
      time when compared to a traditional proportional-integral-derivative algorithm,
      which tends to destabilize with increasing cell density.

PMID- 22610693
TI  - Mexican-American and Puerto Rican breast cancer survivors' perspectives on
      exercise: similarities and differences.
AB  - Qualitative data was collected from Mexican-American (MA) and Puerto Rican (PR)
      breast cancer survivors to gain their perspectives on the relevant issues
      surrounding breast cancer survivorship and exercise. Six focus groups, a total of
      31 participants were convened (three in Puerto Rico and three in Texas).
      Responses were analyzed and compared between the MA and PR groups. Follow-up
      sessions were conducted at the sites to review the initial results and to
      validate a culturally adapted exercise intervention trial. A total of 900
      responses were catalogued into 27 codes. Both groups had similar descriptions of
      exercise and barriers to exercise. Both groups expressed lack of information
      regarding their exercise capabilities. The groups differed in their responses to
      perceived safety in their community and how to deliver a culturally adapted
      exercise intervention in their community. We found important cultural differences
      and similarities in relevant factors of exercise and breast cancer survivorship.

PMID- 22610695
TI  - Hoechst increases adeno-associated virus-mediated transgene expression in airway
      epithelia by inducing the cytomegalovirus promoter.
AB  - BACKGROUND: In airway epithelia, the kinetics of recombinant adeno-associated
      virus (AAV) transgene expression is slow. This has negative practical
      implications for research, as well as for translation into therapy. The DNA minor
      groove-binding agent Hoechst-33342 has been shown to enhance AAV transgene
      expression. In the present study, we investigated the mechanism of Hoechst
      related augmentation of AAV-mediated transgene expression. METHODS: We
      investigated the effect of Hoechst-33342 on HT1080, COS-7, mouse and human airway
      epithelia transduced with different AAV serotypes encoding enhanced green
      fluorescent protein (eGFP). We exposed cells to increasing concentrations of
      Hoechst-33342 at different time points. We evaluated the effect on second-strand
      DNA synthesis using AAV with a self-complementary genome. We also investigated
      the effect on expression from transfected plasmids with and without AAV2 inverted
      terminal repeats (ITRs). RESULTS: We found that Hoechst-33342 significantly
      accelerated AAV transgene expression for all serotypes tested. Hoechst-33342 only
      had an effect when the treatment was given during or after transduction, even 120
      days post-transduction, suggesting an effect on transgene expression regulation.
      Hoechst-33342 increased transgene expression when cells were transduced with a
      self-complementary AAV with the cytomegalovirus promoter, although there was no
      effect on cells transduced with conventional single-stranded AAV encoding the
      Rous sarcoma virus promoter. Finally, Hoechst-33342 increases gene expression
      from transfected plasmids regardless of the presence of AAV2 ITRs. CONCLUSIONS:
      Hoechst dramatically augments and accelerates AAV-mediated transgene expression
      in airway epithelia without altering AAV-mediated gene transfer. Hoechst
      activation of the cytomegalovirus promoter is seen in plasmids, although it is
      drastically enhanced in the context of AAV.

PMID- 22610696
TI  - Boceprevir dosing for late responders and null responders: the role of bridging
      data between treatment-naive and -experienced subjects.

PMID- 22610697
TI  - Molecular characterization of the transition to mid-life in Caenorhabditis
      elegans.
AB  - We present an initial molecular characterization of a morphological transition
      between two early aging states. In previous work, an age score reflecting
      physiological age was developed using a machine classifier trained on images of
      worm populations at fixed chronological ages throughout their lifespan. The
      distribution of age scores identified three stable post-developmental states and
      transitions. The first transition occurs at day 5 post-hatching, where a
      significant percentage of the population exists in both state I and state II. The
      temperature dependence of the timing of this transition (Q 10 ~ 1.17) is too low
      to be explained by a stepwise process with an enzymatic or chemical rate-limiting
      step, potentially implicating a more complex mechanism. Individual animals at day
      5 were sorted into state I and state II groups using the machine classifier and
      analyzed by microarray expression profiling. Despite being isogenic, grown for
      the same amount of time, and indistinguishable by eye, these two morphological
      states were confirmed to be molecularly distinct by hierarchical clustering and
      principal component analysis of the microarray results. These molecular
      differences suggest that pharynx morphology reflects the aging state of the whole
      organism. Our expression profiling yielded a gene set that showed significant
      overlap with those from three previous age-related studies and identified several
      genes not previously implicated in aging. A highly represented group of genes
      unique to this study is involved in targeted ubiquitin-mediated proteolysis,
      including Skp1-related (SKR), F-box-containing, and BTB motif adaptors.

PMID- 22610699
TI  - The APTIMA HPV assay versus the Hybrid Capture 2 test in triage of women with ASC
      US or LSIL cervical cytology: a meta-analysis of the diagnostic accuracy.
AB  - Testing for DNA of 13 high-risk HPV types with the Hybrid Capture 2 (HC2) test
      has consistently been shown to perform better in triage of women with cervical
      cytology results showing atypical squamous cells of undetermined significance
      (ASC-US) but often not in triage of low-grade squamous intraepithelial lesions
      (LSIL) detected in cervical cancer screening. In a meta-analysis, we compared the
      accuracy of the APTIMA HPV test, which identifies RNA of 14 high-risk HPV types,
      to HC2 for the triage of women with ASC-US or LSIL. Literature search-targeted
      studies where the accuracy of APTIMA HPV and HC2 for detection of underlying
      CIN2/3+ was assessed concomitantly including verification of all cases of ASC-US
      and LSIL. HSROC (Hierarchical Summary ROC) curve regression was used to compute
      the pooled absolute and relative sensitivity and specificity. Eight studies,
      comprising 1,839 ASC-US and 1,887 LSIL cases, were retrieved. The pooled
      sensitivity and specificity of APTIMA to triage ASC-US to detect underlying CIN3
      or worse was 96.2% (95% CI = 91.7-98.3%) and 54.9% (95% CI = 43.5-65.9%),
      respectively. APTIMA and HC2 showed similar pooled sensitivity; however, the
      specificity of the former was significantly higher (ratio: 1.19; 95% CI = 1.08
      1.31 for CIN2+). The pooled sensitivity and specificity of APTIMA to triage LSIL
      were 96.7% (95% CI = 91.4-98.9%) and 38.7% (95% CI = 30.5-47.6%) for CIN3+.
      APTIMA was as sensitive as HC2 but more specific (ratio: 1.35; 95% CI = 1.11
      1.66). Results were similar for detection of CIN2 or worse. In both triage of ASC
      US and LSIL, APTIMA is as sensitive but more specific than HC2 for detecting
      cervical precancer.

PMID- 22610701
TI  - Repairing facial injury with refining plastic surgery techniques.
AB  - The purpose of this study was to evaluate the refining plastic surgery techniques
      for repairing facial surface injury. For this purpose, 82 patients with facial
      surface injury were recruited in the study. All wounds were repaired by refining
      plastic surgery techniques. The wounds were processed by fine wound excision and
      plastic surgery repair technique. The deep tissue fracture and dislocation were
      sutured and reduced using 8-0 absorbable suture and the skin wounds were sutured
      using 8-0 cosmetic suture. The facial injuries showed good rates of healing with
      fine debridement and fine recovering. The minimum scarring was observed and good
      cosmetic effect was achieved. We conclude that refining plastic surgery
      techniques including fine debridement and fine recovering are ideal for the
      reconstruction of facial injuries.

PMID- 22610700
TI  - Edible seaweed, Eisenia bicyclis, protects retinal ganglion cells death caused by
      oxidative stress.
AB  - The purpose of the present study was to determine whether edible seaweed, Eisenia
      bicyclis, is effective in blunting the negative influence of N-methyl-D-aspartate
      (NMDA) on rat retinas and of oxidative stress-induced transformed retinal
      ganglion cell (RGC-5 cell line) death. The ethanol extract of E. bicyclis (EEEB)
      significantly attenuated the negative insult of L: -buthionine-(S,R)-sulfoximine
      plus glutamate on RGC-5 cells. Treatment of the RGC-5 cells with EEEB reduced the
      reactive oxygen species and recovered the reduced glutathione level caused by
      various radical species such as H(2)O(2), OH., or O(2).(-). Moreover, EEEB
      inhibited lipid peroxidation on rat brain homogenates caused by sodium
      nitroprusside. Applying NMDA to the retina affected the thickness of the inner
      plexiform layer (IPL) and terminal deoxynucleotidyl transferase-mediated dUTP
      nick-end labeling (TUNEL) produced a positive effect on ganglion cells.
      Importantly, EEEB protected the thinning of IPL and increased TUNEL positive
      cells in the ganglion cell layer (GCL). Five phlorotannin derivatives were
      isolated using chromatographic methods and liquid chromatography-mass
      spectroscopy analysis which has been known as an antioxidant. In conclusion, EEEB
      has a neuroprotective effect in vitro and in vivo. Furthermore, the major
      constituents of this extract, phlorotannins, could possibly be active compounds
      due to their antioxidative potency.

PMID- 22610702
TI  - Development of modified diagnostic criteria for bacterial vaginosis at peripheral
      health centres in developing countries.
AB  - INTRODUCTION: Bacterial vaginosis (BV) is the commonest cause of abnormal vaginal
      discharge in women of child-bearing age and is associated with increased
      susceptibility to HIV-AIDS and sexually transmitted diseases. In obstetrics, BV
      has been implicated in causing various complications. In clinical practice, BV is
      diagnosed using Amsel criteria and Nugent scoring. Using modified Amsel criteria,
      we determined that the fulfilling of any two instead of three criteria can be
      diagnostic of BV. METHODOLOGY: This prospective cross-sectional study involved
      pregnant females complaining of excessive vaginal discharge admitted in a
      tertiary health centre in central India. Four vaginal swabs were collected for
      the diagnosis of BV by Amsel criteria, modified Amsel criteria, and Nugent
      scoring on Gram stain. The sensitivity, specificity, positive predictive value
      (PPV), negative predictive value (NPV), and diagnostic accuracy of each
      individual criterion and combinations of criteria were calculated by using Nugent
      scoring as the gold standard and by chi square test. RESULTS: In the present
      study overall prevalence of BV was 12%. The sensitivity of individual or a
      combination of two criteria was almost same or higher than that of Amsel
      criteria. Specificity of each combination of criteria was comparable to that of
      Amsel criteria. However, a combination of high pH and amine odor test had the
      highest sensitivity (88%) and highest PPV (62%). Diagnostic accuracy of all
      combinations in our study was equal to or slightly higher than that of Amsel
      criteria. CONCLUSION: Diagnostic accuracy of new modified Amsel criteria is as
      reliable as that of Amsel criteria.

PMID- 22610703
TI  - Risk factors for Shiga toxin-producing Escherichia coli infections in
      preadolescent schoolchildren in Buenos Aires, Argentina.
AB  - INTRODUCTION: Shiga toxin-producing Escherichia coli (STEC) infections are the
      leading cause of hemolytic uremic syndrome (HUS). STEC is the most common cause
      of acute kidney disease, responsible for 20% of renal transplants in Argentina.
      METHODOLOGY: In 2007, an epidemiological survey was conducted among 883 students
      from the fifth and sixth years of elementary education in the public schools of
      San Martin City, Buenos Aires, Argentina. Degree of exposure to the known risk
      factors previously detected in the region as primary causes of STEC infections
      was evaluated. Risk factors assessed included consumption of hamburgers, poor
      personal hygiene, and exposure to various types of drinking and recreational
      water. The study was designed to evaluate exposure to risk factors for STEC
      infections among different socioeconomic groups. RESULTS: Ninety-five percent of
      children surveyed reported consumption of hamburgers. Most of these hamburgers
      were precooked. Children of high and medium strata attended private swimming
      pools, while children from the low stratum attended public pools. Only 30.2% of
      students washed their hands after going to the toilet and only 43.5% reported
      hand-washing before eating. CONCLUSIONS: Students demonstrated high levels of
      exposure to identified risk factors for STEC infections. Reduction of these risks
      will require cultural changes aimed at decreasing morbidity caused by food-borne
      infections. Institutional framework must provide the necessary resources to
      implement these changes and emphasize the importance of good personal hygiene.
      Health education must be implemented to increase food safety awareness of the
      consumers.

PMID- 22610704
TI  - A retrospective study of community-acquired Salmonella infections in patients
      attending public hospitals in Lagos, Nigeria.
AB  - INTRODUCTION: A retrospective cohort study on Salmonella-associated diseases
      (SADs) was conducted in 14 public hospitals across Lagos State, Nigeria, between
      1999 and 2008. METHODOLOGY: Medical records of clinically diagnosed patients with
      confirmed Salmonella infections were reviewed for the 10-year period. Laboratory
      diagnosis of typhoid fever cases in all the hospitals were first based on Widal
      agglutination tests then followed by culture, while non-typhoidal Salmonella
      infections were based on culture technique. RESULTS: A total of 85,187 confirmed
      cases of SADs were found, of which 880 deaths were recorded (case-fatality rate =
      1.03% / 10 years). The mean incidence of SADs in Lagos State for the 10-year
      period was estimated at 45 cases per 100,000 persons/year, while that of typhoid
      fever alone was 16 cases per 100,000 persons/year. During the studied period, the
      number of deaths due to typhoid fever was significantly (P < 0.05) higher than
      deaths due to gastroenteritis except in 2003 and 2004. Risk associated with
      typhoidal deaths was 4 to 11 times greater when compared to gastroenteritis
      deaths between 2000 and 2002. Salmonella-associated diseases were most prevalent
      in adults 21 to 30 years of age (49.49%). Cases of patients with invasive
      Salmonella-associated gastroenteritis were observed mainly in children under five
      years of age. CONCLUSION: The current surveillance data indicated high incidence
      of SADs in areas exposed to environmental contaminations. This study revealed
      that infections caused by Salmonella enterica serovars are endemic in our
      environment thus poses a serious threat to public health. Constant public health
      education is essential to avert undue epidemics.

PMID- 22610705
TI  - Comparison of four serological assays for the diagnosis of Chlamydia trachomatis
      in subfertile women.
AB  - INTRODUCTION: Chlamydia antibody testing (CAT) in serum has been introduced as a
      screening method in the infertility workup. We evaluated the test characteristics
      of two ELISA tests compared to micro-immunofluorescence tests (MIFs). MIFs are
      considered the gold standard in the C. trachomatis IgG antibodies detection. We
      also compared the accuracy of all CAT tests in predicting tubal subfertility,
      using laparoscopy as a reference. METHODOLOGY: Four commercial serological
      methods were used to analyse 101 serum samples for the presence of C. trachomatis
      IgG antibodies from patients at the Infertility Clinic of Ghent University
      Hospital. The diagnostic utility for prediction of tubal infertility of
      serological methods was evaluated based on patients' medical records. RESULTS: A
      comparison of the serological assays showed  little difference  in the major
      performance characteristics: the sensitivities of all MIFs and ELISAs were 100%
      for all assays (except the ELISA Vircell, with a sensitivity of 90%), and the
      specificities ranged from 92% for MIF Ani Labsystems to 98% for the MIF Focus and
      ELISA Vircell. As compared to laparoscopy data, CAT positivity in subfertile
      women with tubal damage (n=40) did not significantly differ from that of
      subfertile women without tubal damage (n=61): Positive predictive values (PPV) of
      CAT ranged from 53% to 60% and negative predictive values (NPV) ranged from 62%
      to 64%.  CONCLUSION: evaluated ELISAs are comparable to MIFs in the detection of
      C. trachomatis IgG antibodies and should be preferred for large serological
      studies, especially in resource poor settings.

PMID- 22610706
TI  - Study on biofilm-forming properties of clinical isolates of Staphylococcus
      aureus.
AB  - INTRODUCTION: The purpose of this study was to observe the formation of biofilm,
      an important virulence factor, by isolates of Staphylococcus aureus (S. aureus)
      in Pakistan by different conventional methods and through electron microscopy.
      METHODOLOGY: We screened 115 strains of S. aureus isolated from different
      clinical specimens by tube method (TM), air-liquid interface coverslip assay
      method, Congo red agar (CRA) method, and scanning electron microscopy (SEM).
      RESULTS: Out of 115 S. aureus isolates, 63 (54.78%) showed biofilm formation by
      tube method. Biofilm forming bacteria were further categorized as high producers
      (n = 23, 20%) and moderate producers (n = 40, 34.78%). TM coordinated well with
      the coverslip assay for strong biofilm-producing strains in 19 (16.5%) isolates.
      By coverslip method, weak producers were difficult to differentiate from biofilm
      negative isolates. Screening on CRA showed biofilm formation only in four (3.47%)
      strains. Scanning electron micrographs showed the biofilm-forming strains of S.
      aureus arranged in a matrix on the propylene surface and correlated well with the
      TM. CONCLUSION: Biofilm production is a marker of virulence for clinically
      relevant staphylococcal infections. It can be studied by various methods but
      screening on CRA is not recommended for investigation of biofilm formation in
      Staphylococcus aureus. Electron micrograph images correlate well with the biofilm
      production as observed by TM.

PMID- 22610707
TI  - The prevalence of congenital and perinatal cytomegalovirus infections among
      newborns of seropositive mothers.
AB  - INTRODUCTION: This study aimed to determine the prevalence of congenital and
      perinatal human cytomegalovirus (HCMV) infections among newborns in two major
      neonatal intensive care units (NICU) in Bahrain. METHODOLOGY: One hundred
      newborns comprised of 84 preterm and 16 term babies admitted to the NICUs were
      enrolled in the study. During the first six weeks of life, urine and saliva was
      obtained from the babies weekly and serial breast milk samples were obtained from
      the mothers. Maternal serum HCMV IgG was measured. Virus isolation and detection
      was done by shell vial culture and nested PCR. RESULTS: Maternal HCMV IgG
      seropositivity was 100%. Eight HCMV infections were detected comprising of three
      congenital and five perinatal infections. Congenital HCMV infection was found in
      preterm (2/84; 1.9%) and term (1/16; 6.3%) babies. HCMV DNA was detected in
      breast milk samples obtained during the first 10 days postpartum from all mothers
      whose babies had congenital HCMV. Forty-nine women provided breast milk samples
      between four and six weeks post-partum and HCMV DNA was detected in the breast
      milk of 11 women. Five (45.5%) of these eleven were mothers of babies with
      perinatal HCMV infection. There was no significant difference in the detection of
      HCMV using shell vial culture versus nested PCR method. CONCLUSION: The findings
      indicate occurrence of congenital and perinatal HCMV transmission in this setting
      of high maternal seropositivity. The use of shell vial culture and PCR
      amplification for HCMV screening in the NICU for rapid detection of infection
      during the early postnatal period is recommended. 

PMID- 22610698
TI  - Hybrid nanoparticles for detection and treatment of cancer.
AB  - There is currently considerable effort to incorporate both diagnostic and
      therapeutic functions into a single nanoscale system for the more effective
      treatment of cancer. Nanoparticles have great potential to achieve such dual
      functions, particularly if more than one type of nanostructure can be
      incorporated in a nanoassembly, referred to in this review as a hybrid
      nanoparticle. Here we review recent developments in the synthesis and evaluation
      of such hybrid nanoparticles based on two design strategies (barge vs. tanker),
      in which liposomal, micellar, porous silica, polymeric, viral, noble metal, and
      nanotube systems are incorporated either within (barge) or at the surface of
      (tanker) a nanoparticle. We highlight the design factors that should be
      considered to obtain effective nanodevices for cancer detection and treatment.

PMID- 22610708
TI  - Healthcare-associated infections among pediatric oncology patients in Pakistan:
      risk factors and outcome.
AB  - INTRODUCTION: Pediatric oncology patients are at increased risk of contracting
      healthcare-associated infections (HAIs), which are responsible for increased
      morbidity and mortality rates as well as treatment costs.  This study aimed to
      identify the frequency of HAIs among pediatric oncology patients and their
      outcome. METHODOLOGY: Pediatric oncology patients admitted between January 2009
      and June 2010 in a pediatric ward at Aga Khan University Hospital, Karachi,
      Pakistan, who developed HAIs, were analyzed. RESULTS: A total of 90 HAIs were
      identified in 32 patients in 70 admissions. The HAI rate among pediatric oncology
      patients was 3.1/100 admission episodes. Bloodstream infections (63 episodes,
      90.0%) were the most common, followed by urinary tract infection (two episodes,
      2.9%). Gram-positive infections were seen in 54 (60%) patients, followed by Gram
      negative infection in 34 (37.8%), and fungi in 2 (2.8%) cases. Coagulase negative
      staphylococci was the most common Gram-positive and Escherichia coli and
      Pseudomonas aeruginosa were most common Gram-negative infections. Mortality rate
      among pediatric oncology patients who developed HAIs was 12.5% (4/32). Total
      parental nutrition use and length of stay longer than 30 days were the identified
      risk factors associated with increased mortality among pediatric oncology
      patients who developed HAIs. CONCLUSION: We report an HAI rate among pediatric
      oncology patients of 3.1/100 admission episodes with a mortality rate of 12.5% in
      Pakistan. Further studies should be done, especially in the developing world, to
      identify the risk factors associated with increased mortality among pediatric
      oncology patients so that adequate measures can be taken to reduce the mortality
      among these patients.

PMID- 22610709
TI  - Knowledge, attitudes, perceptions, and practices regarding cutaneous larva
      migrans in deprived communities in Manaus, Brazil.
AB  - INTRODUCTION: Hookworm-related cutaneous larva migrans (HrCLM) is a neglected
      parasitic skin disease commonly found in resource-poor communities in tropical
      countries. It is acquired via skin contact with faeces of cats and dogs, and
      causes intense pruritus and significant morbidity. METHODOLOGY: We investigated
      knowledge, attitudes and practices in caregivers of patients with HrCLM by
      performing focus group discussions (FGDs) with 20 mothers of children with HrCLM
      in two endemic urban communities in Manaus, Brazil. Additionally, socio
      demographic data of 70 actively detected HrCLM patients in both areas were
      obtained by using questionnaires. RESULTS: We found that mainly children who
      lived in large households and habitually walked barefoot were affected. Family
      income was low, housing was poor, and food shortage common. In the FGDs, mothers
      described HrCLM as a severely distressing condition with considerable impact on
      individual and family life. CONCLUSION: Inadequate treatment practices and the
      identification of poverty-related obstacles for practical prevention of HrCLM by
      the mothers of affected children indicate that both health education and
      improvement of living conditions are required jointly.

PMID- 22610711
TI  - Characterisation of novel strains of multiply antibiotic-resistant Salmonella
      recovered from poultry in Southern Senegal.
AB  - INTRODUCTION: Non-typhoidal Salmonella (NTS) contamination in poultry and poultry
      products is a major cause of food-borne disease in humans. This study presents
      the molecular epidemiology of NTS isolated from poultry in Senegal. METHODOLOGY:
      A total of 261 NTS recovered from broiler farms, chicken carcasses and street
      vendors were characterized using random amplification of polymorphic DNA (RAPD)
      and multilocus sequence typing (MLST) techniques. RESULTS: We observed 20
      distinct RAPD profiles corresponding to 18 different serotypes. Strains from each
      of these 20 groups were further analysed using MLST. Consequently, 12 new MLST
      alleles and 17 new sequence types were discovered. Three sequence types (S.
      Kentucky ST198, S. Agona ST13 and S. Istanbul ST33) have previously been
      described in Senegal and other countries, suggesting that these clones are
      geographically widely distributed and are circulating in a wide range of hosts.
      Nine clones showed multi-resistance to the most commonly used antibiotics in both
      humans and animals. However, a novel multi-resistant clone of S. Kentucky ST832
      was found. CONCLUSION: This study gives new insights into the genetic diversity
      of NTS in Senegal. Molecular tools remain essential to improve our understanding
      of the epidemiology of NTS by tracking the sources of infection and/or
      contamination.

PMID- 22610712
TI  - Intra- and inter-laboratory evaluation of an improved multiplex-PCR method for
      detection and typing of Salmonella.
AB  - INTRODUCTION: We developed and evaluated a multiplex-PCR method for rapid
      detection of the most common Salmonella serovars in both developed and developing
      countries. Additionally, the stability of the premixed reagents at high room
      temperature was studied. METHODOLOGY: Fifty-two Salmonella strains belonging to
      the collections of the University of Sassari, Italy, and to the University of the
      Basque Country, Spain, and a collection of a hundred blinded strains, were used
      to evaluate the multiplex-PCR. Primers targeting genes STY1599 and fliC were
      selected, and the method was evaluated both intra and inter-laboratories.
      RESULTS: The inter-laboratory reproducibility was 95.92%, with a kappa index of
      0.757 that indicates a substantial agreement and a high accuracy (80.81%). The
      sensitivity, specificity, accuracy and precision indexes for the Salmonella genus
      and S. Typhi targets were maximum, although the targets for Paratyphi A,
      Typhimurium and Enteritidis showed less accuracy. During a seven-week period, hot
      start multiplex-PCR runs were performed with reagents mixed with wax to test
      their stability at 30oC, and no significant variation in the patterns of
      amplification was observed. CONCLUSIONS: An improved multiplex-PCR for rapid
      detection of the most common serovars of Salmonella operable in both developed
      and developing countries has been designed and tested intra and inter
      laboratories. Following a careful optimization protocol will not only allow the
      confirmation of any suspicious colony by the amplification of the Salmonella
      genus target, but also the preliminary adscription to the prevalent serovars.
      Premixed reagents with wax facilitate the throughput and stability of reagents at
      high room temperatures.

PMID- 22610710
TI  - Plasmodium falciparum and intestinal parasitic co-infections in HIV-infected
      patients in Benin City, Edo State, Nigeria.
AB  - INTRODUCTION: Human co-infection with Plasmodium falciparum and helminthes is
      ubiquitous throughout Africa. This study aimed to determine the co-infections of
      Plasmodium falciparum infection in HIV and intestinal parasitic infections, and
      their immunological distribution, in Benin City, Nigeria. METHODOLOGY: A total of
      2,000 stool specimens from HIV-positive patients and 500 controls (HIV-negative
      individuals) were examined for ova, cysts, or parasites using standard
      procedures. In addition, patients' blood samples were analyzed for CD4 counts by
      flow cytometry and examined for Plasmodium falciparum by microscopy. RESULTS: The
      prevalence of single parasitic infection among HIV patients was 18.1% in males
      and 16.9% among females with no significant difference (p = 0.536) while gender
      was a risk factor in multiple parasitic infections (male versus female: 4.2% and
      1.8% OR = 2.384; 95% CI = 1.371, 4.147) (p = 0.0025). Increasing age was not
      associated with increased risk of both single and multiple parasitic infections
      (p = 0.083; p = 0.248). CD4 + T cell count less than 200 cells/ul was a risk
      factor for acquiring single and multiple parasitic infections among HIV patients
      (OR = 5.565; 95% CI = 4.136, 7.486; p = 0.0001; OR = 4.283; 95% CI = 2.424,
      7.566; p = 0.0001). The most common co-infection observed was between Plasmodium
      falciparum and Ascaris lumbricoides 43% (10) among HIV patients. CONCLUSION: This
      study provides evidence of co-infections between Plasmodium falciparum and
      intestinal parasites. Diagnosis of parasitic infections among HIV patients is
      advocated as this will enhance better management of HIV-infected patients.

PMID- 22610713
TI  - Tigecycline and intravenous fosfomycin zone breakpoints equivalent to the EUCAST
      MIC criteria for Enterobacteriaceae.
AB  - INTRODUCTION: Tigecycline and intravenous (i.v.) fosfomycin could be alternative
      therapeutic options for the treatment of carbapenemase-possessing
      Enterobacteriaceae bacterial infections. However, routine laboratories are forced
      to test these drugs using minimum inhibitory concentration (MIC) methods as zone
      breakpoints are not available for the disc diffusion technique. METHODOLOGY:
      Clinical and Laboratory Standards Institute methods for agar dilution and disc
      diffusion were compared to determine tentative zone breakpoints that best
      correlate to tigecycline and i.v. fosfomycin MIC breakpoints defined by the
      European Committee on Antimicrobial Susceptibility Testing. A total of 195
      Enterobacteriaceae with defined mechanisms of resistance were tested in duplicate
      assays. Half of the strains were characterized as carbapenemase producers (KPC-2,
      OXA-48, OXA-163, VIM-1, VIM-2, IMP-8, NDM-1). RESULTS: Corresponding zone
      diameters of susceptible >= 15 mm, resistant <= 12mm and susceptible >= 17 mm,
      resistant <= 15 mm for the 50 ug fosfomycin plus 50 ug glucose-6-phosphate and
      200 ug fosfomycin plus 50 ug glucose-6-phosphate discs, respectively, allowed
      categorization of the strains with an acceptable level of error (< 10% minor
      errors, < 1.5 % major errors, < 1% very major errors and categorical agreement >
      90%). For the 15 ug tigecycline disc, the best performance was achieved with the
      corresponding zone diameters of susceptible >= 21 mm and resistant <= 16 mm,
      which eliminated the very major and major errors but not the minor errors
      (34.4%). CONCLUSIONS: Based on these results, tigecycline and fosfomycin can be
      included in the routine panel of antibiotics for susceptibility testing by disc
      diffusion to provide fast and reliable information for the selection of treatment
      alternatives, especially for strains with extreme resistance, as carbapenemase
      producers.

PMID- 22610714
TI  - Detection of carbapenem-resistant Escherichia coli and Klebsiella pneumoniae
      producing NDM-1 in Lebanon.
AB  - Carbapenem resistance has been encountered globally with poor outcome of infected
      patients. NDM-1 (New Delhi metallo-beta-lactamase) gene containing organisms have
      emerged and are now spreading in all continents. This is the first report of
      Iraqi patients referred to Lebanon from whom carbapenem resistant
      Enterobacteriaceae were recovered. The genes involved in carbapenem resistance
      were bla-OXA-48 and the novel NDM-1. This report highlights the alarming
      introduction of such resistance among Enterobacteriaecae to this country.

PMID- 22610715
TI  - Plasmid-mediated quinolone resistance determinant qnrB19 in non-typhoidal
      Salmonella enterica strains isolated in Venezuela.

PMID- 22610716
TI  - Radiation dose exposure of patients undergoing 320-row cardiac CT for assessing
      coronary angiography and global left ventricular function.
AB  - A 320-row multidetector CT provides the capability for prospective
      electrocardiogram (ECG)-gated coronary CT angiography (CTA) and tube current
      modulated cardiac function assessment (CFA). We assessed and compared the
      effective radiation dose of these two modes. On a prospective basis, we performed
      ECG-gated cardiac CT on 119 patients (87 were males). For heart rates (HRs) </=65
      beats/min (bpm), we used one-heartbeat acquisition and half-scan reconstruction.
      HRs from 66 to 79 bpm and >/=80 bpm were scanned with either two or three
      heartbeats acquisitions, respectively. We used two types of scans. One type was
      based on a prospective ECG-gated CTA mode and the other using a tube current
      modulated CFA mode covering an entire R-R interval. The mean BMI of patients was
      25.4 (range 18.8-49.3). Fifty-one patients (42.9 %) underwent CFA scanning, while
      the remaining 68 (57.1 %) had CTA. The majority of patients completed the scan in
      a single heartbeat (59.7 %). The mean dose of CTA mode at 65-85 % phase window
      for one and two heartbeats was 3.68 mSv (2.40-7.23) and 8.61 mSv (6.76-10.60),
      respectively. The mean dose of CFA mode for a single heartbeat measurement with
      dose modulation (25 % dose for CFA, and 100 % dose during 65-85 % phase window
      for CTA) was 6.32 mSv (4.69-8.89). CTA with prospective ECG-gating allows for
      acceptable image quality and radiation dose. HR reduction is mandatory to
      minimize radiation exposure. Global left ventricle function can be assessed with
      a single heartbeat within an acceptable radiation dose.

PMID- 22610717
TI  - Spectral domain optical coherence tomography evolutive features in acute macular
      neuroretinopathy.
AB  - PURPOSE: To demonstrate the usefulness of spectral domain optical coherence
      tomography (SD-OCT) in investigating the evolution of the retinal outer lesions
      seen in acute macular neuroretinopathy (AMN). METHODS: A 32-year-old woman
      presented with a 1-day history of paracentral dark spot in the left eye, preceded
      by a flulike illness. A full ophthalmologic examination, color vision, visual
      field examination, and conventional imaging of the retina were done. Scanning
      laser ophthalmoscopic infrared imaging and SD-OCT of the macular region were
      performed. RESULTS: Best-corrected visual acuity was 20/20 in both eyes. Slit
      lamp examination as well as retinal photographs were unrevealing. Scanning laser
      ophthalmoscopic infrared examination showed a dark, sharp, oval area in the
      macular region that corresponded to a rounded patch drawn by the patient on an
      Amsler grid. The SD-OCT showed focal highly reflective lesion of outer plexiform
      layer (OPL) extending to the outer nuclear layer. After recovery of the OPL,
      follow-up SD-OCT showed an associated disruption of the external limiting
      membrane and the retinal pigment epithelium inner band as well as thinning of the
      inner segment/outer segment junction. Retinal inner layers were otherwise normal.
      CONCLUSIONS: Spectral domain optical coherence tomography is of particular
      interest in the diagnosis of AMN. It is also very useful in featuring the
      chronological events happening in the outer retina. As the lesions shown are
      confined to the outer layers, this condition should be called acute macular outer
      retinopathy rather than AMN.

PMID- 22610718
TI  - Causes of IOL explantation in Spain.
AB  - PURPOSE: To study the reasons and the demography of pseudophakic intraocular lens
      (IOL) explantation in Spain. METHODS: In this observational multicenter
      retrospective study, the cases studied correspond to the 15 centers that
      constitute the Nodo Calidad Visual y Cirugia Refractiva of the Red Tematica de
      Investigacion Cooperativa (RETICS) sponsored by the Spanish Ministry of Health.
      Clinical data from all the patients who underwent explantation were assessed. The
      different reasons that caused the decision of explantation were analyzed.
      RESULTS: A total of 257 explanted pseudophakic IOLs have been studied. Patients'
      mean age when explantation occurred was 67.5 years (SD 13.5 [22-99]) and 135 were
      female (52.5%). The main causes for explantation were dislocation/decentration in
      145 cases (56.3%), incorrect lens power in 33 cases (12.8%), IOL opacification in
      29 eyes (11.3%), neuroadaptation failure in 16 cases (6.2%), pseudophakic bullous
      keratopathy in 6 eyes (2.3%), endophthalmitis in 5 cases (1.9%), and "other
      causes" in 23 eyes (8.9%). Treatment after explantation was posterior chamber IOL
      implantation in 149 eyes (58%), anterior chamber IOL implantation in 49 eyes
      (19.1%), aphakia in 39 eyes (15.2%), and missing information in 20 cases (7.8%).
      Mean time from implantation to explantation was 3.97 (SD 4.68 [0.005-21.1])
      years. CONCLUSIONS: Dislocation/decentration (most of the time with lens in the
      bag) is the main cause for explantation in Spain, followed by incorrect lens
      power (which decreased greatly over past years) and IOL opacification. Posterior
      chamber IOL implantation is the most elected treatment after explantation.

PMID- 22610719
TI  - Quantitative analysis of anterior chamber following peripheral laser iridotomy
      using Pentacam in eyes with primary angle closure.
AB  - Purpose. To quantify the effects of laser peripheral iridotomy (LPI) on
      peripheral anterior chamber depth (PACD), central internal anterior chamber depth
      (CACD), and anterior chamber volume (ACV) using Rotating Scheimpflug Imaging
      System, i.e., Pentacam, on Asian Indian eyes. Methods and Materials. This was an
      institutional, prospective, nonrandomized, interventional study. Sixty-eight eyes
      of 68 consecutive patients with primary angle closure were enrolled. Pentacam
      scanned the anterior ocular segment with the 25-image acquisition scan protocol
      and PACD, CACD, and ACV values were obtained. The PACD was measured in nasal,
      temporal, superior, and inferior meridian at 4 mm and 8 mm circles. Nd:YAG laser
      iridotomy was performed. Preiridotomy, immediate postiridotomy, 1 week and 1
      month postiridotomy data for PACD, CACD, and ACV were acquired. The t test and
      repeated-measures analysis of variance (ANOVA) and one-way ANOVA were used for
      statistical significance. Results. Pre-LPI ACV increased immediately after
      iridotomy (28.4 mm3; p=0.001), at 1 week (15.9 mm3; p=0.001), and at 1 month post
      LPI (19.8 mm3; p=0.00). There was no change in CACD (p>0.05). Significant PACD
      deepening was observed at 4 mm and 8 mm in all meridians (p<0.001) at all visits.
      Conclusions. Laser peripheral iridotomy significantly increased the PACD and ACV.
      Extent of the LPI-induced PACD increase was enhanced with increasing distance
      from the optical axis.

PMID- 22610720
TI  - Sulcus implantation of a single-piece foldable acrylic intraocular lens after
      posterior capsular rupture in cataract surgery.
AB  - PURPOSE: To evaluate the safety of a foldable acrylic single-piece intraocular
      lens (IOL) in cases of complicated cataract surgery and sulcus implantation. The
      setting was University and private anterior segment surgery practices. METHODS:
      In this observational case series study, 13 eyes of 13 patients were included
      after complicated phacoemulsification with extensive posterior capsule rupture
      with or without vitreous loss. A foldable acrylic single-piece IOL (Rayner
      Superflex 620H; Rayner Intraocular Lenses Limited, Hove, East Sussex, UK) was
      implanted in the ciliary sulcus in each eye. Postoperative follow-up included
      best-corrected visual acuity, anterior segment biomicroscopy, IOL centration and
      position, intraocular pressure, and fundus biomicroscopy. Optical coherence
      tomography was performed in 2 subjects. Median follow-up time was 12 months
      (range 1-21 months). RESULTS: Visual acuity 12 months after surgery was 6/18 and
      below in 5 eyes (39%), between 6/12 and 6/7.5 in 6 eyes (46%), and 6/6 in 2 eyes
      (15%). All patients experienced vision improvement. Postoperative complications
      included corneal edema (2 eyes), Descemet folds (1 eye), intraocular pressure
      elevations (3 eyes), and pronounced anterior segment inflammation (1 eye). Two
      eyes had minor pupil contour abnormalities. No significant IOL decentration was
      observed. CONCLUSIONS: Sulcus implantation of a foldable acrylic single-piece IOL
      in eyes with complicated cataract surgery maintains the advantages of easy
      insertion and small incision. Postoperatively, all IOLs were centered, visual
      results were good, and complications were manageable and not IOL-related.

PMID- 22610721
TI  - Spontaneous hemorrhagic Descemet membrane detachment causing pupillary block.
AB  - PURPOSE: To present a unique case of a 65-year-old man using warfarin who
      presented with acute unilateral loss of vision due to hemorrhagic Descemet
      membrane detachment (DMD) with pupillary block and elevated intraocular pressure
      and its subsequent treatment and challenges. METHOD: Case report. RESULTS:
      Clinical examination showed a visual acuity of finger counting, central DMD with
      near contact to the iris and premembrane hemorrhage, an intraocular pressure
      (IOP) of 19 mmHg, and normal pupillary reaction. An International Normalized
      Ratio (INR) of 4.9 was treated with dose reduction and vitamin K. Twelve hours
      later the patient re-presented with an acute increase in pain and an IOP of 78
      mmHg with pupillary block and iris bombe. YAG-laser membranotomy, anterior
      chamber paracentesis, and maximal topical and systemic therapy were unsuccessful
      in reducing the IOP. Surgical management, including irrigation and aspiration of
      blood, led to a normalization of the IOP. Descemet stripping automated
      endothelial keratoplasty (DSAEK) resulted in a visual acuity of 0.3. Deep
      stromal/pre-Descemet membrane neovascularization was found bilaterally,
      suspicious for a previous interstitial keratitis. CONCLUSIONS: The previously
      unreported complication of pupillary block following a pre-Descemet membrane
      hemorrhage was treated successfully for the first reported time, in a 2-step
      DSAEK. This indicates that DSAEK could be considered as a treatment option for
      DMD, especially in traumatic circumstances.

PMID- 22610722
TI  - Fertility treatments, congenital malformations, fetal loss, and childhood acute
      leukemia: the ESCALE study (SFCE).
AB  - BACKGROUND: This study investigated the relationships between childhood acute
      leukemia (AL) and selective maternal and birth characteristics, including
      congenital malformations and the use of fertility treatment, for which the
      literature remains scarce. PROCEDURE: The national registry-based case-control
      study ESCALE was carried out in France in 2003-2004. Population controls were
      frequency matched with cases on age and gender. Data were obtained from
      structured telephone questionnaires. Odds ratios (OR) and their 95% confidence
      intervals were estimated using unconditional regression models adjusted for
      potential confounders. RESULTS: In all, 764 cases of AL (648 lymphoblastic AL
      (acute lymphoblastic leukemia, ALL) and 101 myeloblastic AL) and 1,681 controls
      were included. The AL cases' mothers reported congenital malformations more
      frequently than the controls' mothers (OR = 1.5 [1.0-2.4]). ALL was significantly
      associated with the use of fertility treatment for the index pregnancy (OR = 1.9
      [1.3-2.8]). In particular, ALL was associated with ovulation induction only (OR =
      2.6 [1.6-4.3]), but not with in vitro fertilization (IVF, OR = 1.0 [0.4-2.3]) or
      artificial insemination (OR = 1.3 [0.5-3.9]). A positive association was also
      observed for the difficulty of becoming pregnant without fertility treatment (OR
      = 1.5 [1.0-2.1]). AL was positively associated with a history of voluntary
      abortion (OR = 1.4 [1.1-1.8]) but not with a history of spontaneous (OR = 0.8
      [0.7-1.0]) or therapeutic (OR = 0.7 [0.5-1.1]) abortion. CONCLUSION: The results
      suggest that subfertility in itself and ovulation induction may be associated
      with ALL, and support a positive association with congenital malformations. The
      links with the various types of fertility drugs and the underlying causes of
      infertility need to be investigated further.

PMID- 22610723
TI  - Guanfacine extended release as adjunctive therapy to psychostimulants in children
      and adolescents with attention-deficit/hyperactivity disorder.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral
      disorder associated with a wide range of impairments. Psychostimulants are
      generally first-line pharmacotherapy, but symptom improvement is suboptimal in
      some patients. In these patients, clinicians frequently use a combination of
      psychostimulants and nonscheduled medications to manage ADHD, although published
      evidence supporting this practice was relatively scarce until recently.Guanfacine
      extended release (GXR), a selective alpha2A-adrenoceptor agonist, is approved as
      a monotherapy and adjunctive therapy to psychostimulant medications for ADHD in
      patients 6-17 years of age. Drug-drug interaction studies have demonstrated that
      the adjunctive administration of GXR with a long-acting methylphenidate
      preparation or lisdexamfetamine dimesylate did not change exposure to the active
      components of either medication in a clinically meaningful way compared with
      either treatment alone.Data supporting the potential efficacy of GXR adjunctive
      to psychostimulants were preliminarily observed in a 9-week, open-label, dose
      escalation study and subsequent extension study (<= 24 months) in subjects aged 6
      17 years with suboptimal control of ADHD symptoms on psychostimulant monotherapy.
      In a subsequent 9-week, randomized, double-blind, placebocontrolled study of
      subjects aged 6-17 years with suboptimal response to a long-acting,
      extendedrelease, oral psychostimulant, adjunctive GXR (administered in the
      morning or evening) was associated with significantly greater symptom reduction
      than placebo and psychostimulant (ADHD Rating Scale IV [ADHD-RS-IV] total score,
      placebo-adjusted least squares mean reductions: GXR AM, -4.5, P = 0.002; GXR PM, 
      5.3, P < 0.001, based on Dunnett's test). Across multiple studies, the safety and
      tolerability profile of GXR administered adjunctively to psychostimulants has
      been consistent with the known profiles of each medication. Additional studies
      should further explore the role of adjunctive GXR in clinical practice to help
      identify those patients most likely to benefit from such therapy.

PMID- 22610724
TI  - The detection of heterozygous familial hypercholesterolemia in Ireland.
AB  - Heterozygous familial hypercholesterolemia (HeFH) is an autosomal dominant
      condition with a population prevalence of 1 in 500, and is associated with
      significant cardiovascular morbidity and mortality. It may be caused by mutations
      in the low-density lipoprotein (LDL) receptor, apolipoprotein B100 (Apo B100), or
      proprotein convertase subtilisin/kexin type 9 (PCSK9) genes, with over 1,000
      causative mutations described. Statin therapy in HeFH is considered effective and
      safe. Audit data suggest that approximately 80% of the putative HeFH population
      remains unidentified and, therefore, there is a need to develop a strategy for
      the identification of affected individuals so that early lipid-lowering treatment
      may be offered. There is good evidence showing the effectiveness and
      acceptability of HeFH screening programs in Europe. The authors describe a
      protocol for an all island approach to HeFH detection in the Republic of
      Ireland/Northern Ireland. Index cases will be identified by opportunistic
      screening using the Simon Broome, or Make Early Diagnosis to Prevent Early Death
      (MedPed) and World Health Organization (WHO) criteria. Patients identified as
      "definite," "probable," or "possible" HeFH criteria will be offered genetic
      testing. The authors expect causative mutations to be identified in approximately
      80% of patients with "definite" HeFH but in only approximately 20% of patients
      with "possible" HeFH. Cascade screening will be undertaken in first-degree
      relatives of the index case using genetic testing (where a causative mutation has
      been identified), or otherwise using LDL cholesterol concentration. The
      establishment of a HeFH screening program on an all-island basis will require:
      expansion of the existing molecular genetics diagnostic services, the
      establishment of a cohort of nurses/genetic counselors, a HeFH database to
      support cascade testing, the development of a network of lipid clinics (in a
      primary or secondary care setting), and an educational initiative to raise
      awareness of HeFH among healthcare professionals and the general population.

PMID- 22610725
TI  - Tailored poly(2-oxazoline) polymer brushes to control protein adsorption and cell
      adhesion.
AB  - POx bottle-brush brushes (BBBs) are synthesized by SIPGP of 2-isopropenyl-2
      oxazoline and consecutive LCROP of 2-oxazolines on 3-aminopropyltrimethoxysilane
      modified silicon substrates. The side chain hydrophilicity and polarity are
      varied. The impact of the chemical composition and architecture of the BBB upon
      protein (fibronectin) adsorption and endothelial cell adhesion are investigated
      and prove extremely low protein adsorption and cell adhesion on BBBs with
      hydrophilic side chains such as poly(2-methyl-2-oxazoline) and poly(2-ethyl-2
      oxazoline). The influence of the POx side chain terminal function upon adsorption
      and adhesion is minor but the side chain length has a significant effect on
      bioadsorption.

PMID- 22610726
TI  - Biopiracy and the ethics of medical heritage: the case of India's traditional
      knowledge digital library'.
AB  - Medical humanities have a central role to play in combating biopiracy. Medical
      humanities scholars can articulate and communicate the complex structures of
      meaning and significance which human beings have invested in their ways of
      conceiving health and sickness. Such awareness of the moral significance of
      medical heritage is necessary to ongoing legal, political, and ethical debates
      regarding the status and protection of medical heritage. I use the Indian
      Traditional Knowledge Digital Library as a case study of the role of medical
      humanities in challenging biopiracy by deepening our sense of the moral value of
      medical heritage.

PMID- 22610727
TI  - High-resolution esophageal long-term ECG allows detailed atrial wave morphology
      analysis in case of atrial ectopic beats.
AB  - Detection of arrhythmic atrial beats in surface ECGs can be challenging when they
      are masked by the R or T wave, or do not affect the RR-interval. Here, we present
      a solution using a high-resolution esophageal long-term ECG that offers a
      detailed view on the atrial electrical activity. The recorded ECG shows atrial
      ectopic beats with long coupling intervals, which can only be successfully
      classified using additional morphology criteria. Esophageal high-resolution ECGs
      provide this information, whereas surface long-term ECGs show poor atrial signal
      quality. This new method is a promising tool for the long-term rhythm monitoring
      with software-based automatic classification of atrial beats.

PMID- 22610729
TI  - Cancer therapy with genetically-modified T cells for the treatment of melanoma.
AB  - The aim of this review is to acquaint the reader with the concept of T cell
      receptor (TCR) gene therapy for metastatic melanoma. We first review antigen
      choice, followed by gene delivery technology and, finally, we discuss selected
      clinical applications. To be successful, TCR gene therapy must combine multiple
      elements and research disciplines. First, there is a need for an understanding of
      tumor immunology because this is essential in proper antigen choice. Second, gene
      therapy is a technology-driven field and cutting edge knowledge of protein
      engineering and gene delivery methods are indispensable. Finally, a dedicated
      team of physician/scientists and healthcare providers is fundamental to clinical
      success. TCR gene therapy is now a realistic treatment option for metastatic
      melanoma. Both tumor regression and on-target/off-tumor toxicities have been
      observed, which emphasizes the experimental nature of this approach. As with any
      new medical procedure, future large-scale randomized trials will be necessary to
      validate this approach, and these are within reason in the next few years. This
      article is a US Government work and is in the public domain in the USA.

PMID- 22610728
TI  - Oligomerization of glycine and alanine on metal(II) octacynaomolybdate(IV): role
      of double metal cyanides in prebiotic chemistry.
AB  - Condensation reactions of amino acid (glycine and alanine) on the surface of
      metal(II) octacyanomolybdate(IV) (MOCMo) complexes are investigated using high
      performance liquid chromatography (HPLC) and electron spray ionizations-mass
      spectroscopy (ESI-MS). The series of MOCMo have been synthesized and the effect
      of outer sphere metal ions present in the MOCMo on the oligomerization of glycine
      and alanine at different temperature and time found out. Formation of peptides
      was observed to start after 7 days at 60  degrees C. Maximum yield of peptides
      was found after 35 days at 90  degrees C. It has been found that zinc(II)
      octacyanomolybdate(IV) and cobalt(II) were the most effective metal cations
      present in outer sphere of the MOCMo for the production of high yield of
      oligomerized products. Surface area of MOCMo seems to play dominating parameter
      for the oligomerization of alanine and glycine. The results of the present study
      reveal the role of MOCMo in chemical evolution for the oligomerization of
      biomolecules.

PMID- 22610730
TI  - Accumulation of weathered p,p'-DDTs in hybridized Cucurbita pepo cultivars.
AB  - Cucurbita pepo spp pepo (zucchini) is known as an exceptional weathered
      dichlorodiphenyldichloroethylene (DDE) accumulator, whereas Cucurbita pepo ssp
      ovifera (squash) is termed a nonaccumulator. Experiments were conducted with
      hybridized zucchini and squash to assess the inheritance pattern of DDX (the sum
      of p,p'-dichlorodiphenyltrichloroethane [p,p'-DDT], p,p'
      dichlorodiphenyldichloroethane [p,p'-DDD], and p,p'
      dichlorodiphenyldichloroethylene [p,p'-DDE]) accumulation potential in xylem sap
      and tissues of parental, F1 hybrids, and F1 backcross (BC) generations of plants.
      Plants were grown in pots containing soil with weathered DDX at 732 to 1,130 ng/g
      soil or under field conditions in soil with 322 to 2,700 ng/g. The DDX stem
      bioconcentration factors and xylem sap values showed differences between parental
      and hybridized plants of squash and zucchini. For squash grown in greenhouse
      conditions, the DDX flow rate in the xylem sap was 17.3, 121, and 40.8 ng/h in
      parental, F1 hybrids, and F1 BC plants, respectively. Similarly, the stem DDX
      content of parental, F1, and F1 BC squash was 11, 253, and 96 ng/g (dry wt),
      respectively. A similar inheritance pattern for squash was observed when the
      plants were grown under field conditions. The DDX flow rates in the xylem sap of
      pot-grown parental, F1, and F1 BC zucchini cultivars were 100, 8.5, and 26 ng/hr,
      respectively, and the stem DDX content was 191, 102, and 142 ng/g, respectively.
      Again, similar trends in accumulation potential were observed for hybridized
      zucchini grown under field conditions. The DDX concentrations in parental plants
      matched the expected pattern, with hybrids midway between the two species, and
      the backcross being more like the parent again for both species. This inheritance
      pattern of contaminant accumulation and translocation ability follows classical
      Mendelian segregation and suggests single-gene or single-locus control.

PMID- 22610731
TI  - Changing scenario of postgraduate medical education in Nepal.

PMID- 22610732
TI  - Basic science research in medicine.

PMID- 22610733
TI  - Fostering research skills in undergraduate medical  students through mentored
      students projects: example from an Indian medical school.
AB  - BACKGROUND: Healthcare decision-making is largely reliant on evidence-based
      medicine; building skills in scientific reasoning and thinking among medical
      students becomes an important part of medical education. Medical students in
      India have no formal path to becoming physicians, scientists or academicians.
      OBJECTIVES: This study examines students' perceptions regarding research skills
      improvement after participating in the Mentored Student Project programme at
      Melaka Manipal Medical College, Manipal Campus, India. Additionally, this paper
      describes the initiatives taken for the continual improvement of the Mentored
      Student Project programme based on faculty and student perspectives. METHODS: At
      Melaka Manipal Medical College, Mentored Student Project was implemented in the
      curriculum during second year of Bachelor of Medicine and Bachelor of Surgery
      programme with the intention of developing research skills essential to the
      career development of medical students. The study design was cross-sectional. To
      inculcate the spirit of team work students were grouped (n=3 to 5) and each group
      was asked to select a research project. The students' research projects were
      guided by their mentors. A questionnaire (Likert's five point scale) on students'
      perceptions regarding improvement in research skills after undertaking projects
      and guidance received from the mentor was administered to medical students after
      they had completed their Mentored Student Project. The responses of students were
      summarised using percentages. The median grade with inter-quartile range was
      reported for each item in the questionnaire. The median grade for all the items
      related to perceptions regarding improvement in research skills was 4 which
      reflected that the majority of the students felt that Mentored Student Project
      had improved their research skills. The problems encountered by the students
      during Mentored Student Project were related to time management for the Mentored
      Student Project and mentors. RESULTS: This study shows that students acknowledged
      that their research skills were improved after participating in the Mentored
      Student Project programme. CONCLUSIONS: The Mentored Student Project programme
      was successful in fostering positive attitudes among medical students towards
      scientific research. The present study also provides scope for further
      improvement of the Mentored Student Project programme based on students' and
      faculty perspectives.

PMID- 22610734
TI  - Urological complication after kidney transplantation.
AB  - BACKGROUND: Renal transplantation is a regular service at Tribhuvan University
      Teaching Hospital and complications have been known to occur after it. This study
      was conducted to assess complications after transplantation. OBJECTIVES: To
      determine the incidence of urological complications after living related renal
      transplantation at Tribhuvan University Teaching Hospital. METHODS: A clinical
      study was performed (from August 2008 to July 2010) which included 50 living
      related renal transplantations at Tribhuvan University Teaching Hospital. All the
      donors and recipients were evaluated preoperatively with necessary investigations
      and followed up postoperatively with standard hospital transplant protocol. The
      incidence of urological complications were documented and analyzed. RESULTS:
      Fifty living-related, renal transplantations were carried out during the study
      period. Seven doors had minor post operative complications; three had post
      operative fever, two had chest infections and each one had superficial surgical
      site infections and severe pain at incision site. Ureteroneocystostomy was
      performed with double J stent in all recipients. Urological complications were
      noted in 12 (24%) recipients. Clinical significant hematuria occurred in four
      cases. One patient had ureteric necrosis and urinary leak which required re
      exploration post operatively. Two patients developed delayed ureteric stricture
      which were managed by antegrade Double J stenting and ureteric reimplantation.
      Peri-graft abscess occurred in two cases, which were drained percutaneously.
      surgical site infections was seen in one case. CONCLUSIONS: Urological
      complications are inevitable in renal transplantation and our complications rate
      appears similar to that reported in literature.

PMID- 22610735
TI  - The role of the injection botulinum toxin A in cases of blepharospasm syndrome,
      hemifacial spasm and Meige's syndrome.
AB  - BACKGROUND: Benign Essential Blepharospasm Symdrome is a neuropathologic
      disorder. The cause of blepharospasm is multifactorial. It is unlikely that a
      single defect in this elusive control centre is the primary cause of this
      disease. OBJECTIVES: To evaluate the role of botulinum toxin A in treating cases
      of Essential Blepharospasm Symdrome, Hemifacial Spasm and Meige's Syndrome, and
      to assess orbicularis oculi muscle post treatment, in the patients who attended
      neuro-ophthalmology clinic and the general outpatient department of BP Koirala
      Lions Centre for Ophthalmic studies. METHODS: A prospective, interventional study
      was carried out on all the patients of Essential Blepharospasm Symdrome,
      Hemifacial Spasm and Meige's syndrome who underwent treatment with botulinum
      toxin A in BP Koirala Lions Centre for Ophthalmic studies during a study period
      of one and half years. Pre- treatment grading of the spasm was done with Jankovic
      spasm grading and post treatment response was seen with assessment of orbicularis
      oculi muscle and improvement in functional impairment scale. Relevant findings
      were noted. RESULTS: A total of 40 cases were enrolled in the study. The mean
      Jankovic spasm grading in cases of essential blepharospasm, hemifacial spasm and
      Meige's syndrome was 3.61 (+/- Standard deviation 0.50, range 3-4), 3.21 (+/-
      Standard deviation 0.63, range 2-4) and 3.67 (+/- Standard deviation 0.57, range
      3-4) respectively. The mean value for reappearance of significant spasms (in
      months) in cases of essential blepharospasm, hemifacial spasm and Meige's
      syndrome was 4.3 (+/- Standard deviation 1.6, range 2.0-6.5), 5.8 (+/- Standard
      deviation 1.4, range 3-8) and 4.5 (+/- Std.deviation 2.8, range 2.5-6.5)
      respectively. Blepharoptosis was the commonest complication accounting for 66.6%
      of the complications. CONCLUSIONS: The movement disorders like Essential
      Blepharospasm, Hemifacial Hpasm and Meige's syndrome are treated by different
      modalities. An acceptable and effective treatment modality has been a long felt
      need in these cases. Our study has shown that injection of botulinum toxin A has
      been a safe and effective method of treating these cases in Nepal.

PMID- 22610736
TI  - Nerve conduction study in healthy individuals: a preliminary age based study.
AB  - BACKGROUND: Nerve conduction study assesses peripheral nerve functions and has
      clinical implication. OBJECTIVES: To study the effect of age on nerve conduction
      study variables in healthy adults. METHODS: Cross sectional study was done from
      Jan 2006 to Dec 2006 in department of Physiology, BP Koirala Institute of Health
      Sciences, Dharan, Nepal. The study was done in 34 (younger, n= 18, 17 to 29
      years; older, n= 16, 30 to 57 years) consenting healthy adults of either sex. The
      compound muscle action potential and sensory nerve action potential were recorded
      using standard technique. Due to the non-normal distribution of data, the effect
      of age on nerve conduction study variables was analyzed using Mann Whitney U
      test. RESULTS: Younger vs. older individuals: older had lower Compound Muscle
      action potential amplitude (mV) in all motor nerves except radial and left ulnar
      nerves. Compound Muscle action potential duration (ms) was shorter in older (p
      less than 0.05) in ulnar, tibial, right median and left common peroneal motor
      nerves than the younger: right median (6.92+/-1.3 vs. 8.5+/-1.88), right ulnar
      (7.09+/-1.54vs. 8.2+/-1.31), left ulnar (10.56+/-1.44 vs. 12.06+/-1.5), right
      tibial (6.28+/-0.81vs. 7.28+/-1.12), and left tibial (9.58+/-1.52vs.10.78+/
      1.71). Sensory nerve actional potential amplitude (MUV) was smaller in older as
      compared to younger: right median (19.01+/-7.83 vs. 26.97+/-10.63), right ulnar
      (10.9+/-3.44 vs.16.09+/-5.85) and right radial (14.31+/-4.34 vs.19.72+/-6.47).
      SNAP duration (ms) was longer in older: right ulnar (1.34+/-0.17 vs.1.26+/-
      0.18), left ulnar (1.46+/-0.14 vs. 1.29+/-0.26), and left median (1.11+/- 0.14
      vs. 1+/- 0.14). CONCLUSIONS: Age has definite effects on amplitude and duration
      of motor and sensory nerves. Different nerves have different timing of aging.
      Without adjustment for age, the sensitivity and specificity of nerve conduction
      study will decrease whenusing the same reference data in patients with different
      age.

PMID- 22610737
TI  - A study in awareness about eye health care and eye donation among secondary level
      students of North Kolkata, India.
AB  - BACKGROUND: Corneal blindness is one of the important types of blindness that can
      be prevented by proper health care education and conventionally cured by corneal
      transplantation for which awareness regarding eye donation is essential.
      OBJECTIVES: The aim of the study is to assess the awareness of eye health care
      and eye donation among secondary level school students of North Kolkata. METHODS:
      It was a cross-sectional study. SETTINGS: Eight Government aided schools of North
      Kolkata, West Bengal, India. A total of 1525 students of standard VIII, IX and X
      of Government aided schools of North Kolkata participated in this study. A pre
      tested, semi-structured questionnaire was administered on eye health care and eye
      donation. RESULTS: 1284 (84.2%) participants opined that awareness on eye health
      care can prevent most of the blindness and 1206 (79.1%) students knew that
      Vitamin A has important role in prevention of childhood blindness. Majority, 1235
      (81.0%) students were aware of eye donation after death while only 489 (32.1%)
      participants knew that the ideal time for eye donation is within 6 hours of
      death. 802 (52.6%) participants mentioned printed and electronic media (like
      newspaper and television) as the major source of information on eye donation.
      CONCLUSIONS: Media publicity to increase awareness of eye donation and eye health
      care is not enough. Strategies have to be developed to educate the students, so
      that they can act as motivators for enhancing eye donation and increasing eye
      health care awareness in the community.

PMID- 22610738
TI  - Ambispective study on Mac Donald suturing in pregnant ladies with cervical
      incompetence in Dhulikhel Hospital.
AB  - BACKGROUND: Cervical incompetence is one of the main contributors to repeated
      pregnancy loss, accounting for approximately 25% of the cases. Typically it
      results in progressive cervical dilatation, leading to a painless second- or
      early-third-trimester abortion. OBJECTIVES: The main objective of the study was
      to explore the benefit from cervical cerclage in pregnant women with anatomical
      cervical incompetence. METHODS: In a review of the operation and labour registers
      from January 2006 till January 2010, a total of 38 cervical cerclage procedures
      were performed at Dhulikhel Hospital (DH). In the study caste, parity,
      gestational age, diagnostic criteria, postoperative complications and pregnancy
      outcomes of the cases were analyzed. RESULTS: Two of the 38 cases didn't come for
      delivery at Dhulikhel Hospital (Kathmandu University Teaching Hospital). Four
      women haven't delivered at the time of data analysis. So pregnancy outcomes were
      analyzed among 32 cases while rests of the variables were analyzed among 38
      cases. Of them 18 cases (47%) were Brahmin, 22 cases (58%) were between 20-25
      years old and 32 cases (84%) were from Kavre district. All cases were booked
      cases (they had antenatal care in the hospital) and 14 patients (37%) were third
      gravida. Most cases had 2 to 4 antenatal visits prior to suturing. Two cases were
      diagnosed with a bicornuate uterus. 21 cases (55%) had a previous history of at
      least one dilatation and evacuation. 33 cases (87%) were diagnosed with cervical
      incompetence clinically and confirmed by ultrasound. The remaining 13% were
      assessed, in the absence of a history of midtrimester abortion, of having a high
      suspicion of cervical incompetence after midtrimester scan with measurement of
      cervical length. In 18 cases (47%), cervical cerclage were done at 15 to 20 weeks
      of gestation. The postoperative period was uneventful in all 38 cases. All cases
      (32) delivered in DH were assisted by consultant obstetricians. 19 out 32 cases
      (59%) were delivered vaginally at term. CONCLUSIONS: 38 cases were included in
      the study. Pregnancy outcomes were analyzed among 32 cases while rests of the
      variables were analyzed among 38 cases. 31 out 32 cases were delivered with good
      foetal weight. It clearly shows pregnant women with anatomical cervical
      incompetence were benefitted from cervical cerclage. The authors recommend an
      early trans vaginal scan in any patient with a history of mid trimester abortion
      or preterm labour. The cervical cerclage procedure therefore should be available
      more widely to benefit those patients with proven or strongly suspected cervical
      incompetence.

PMID- 22610739
TI  - Determinants of skilled birth attendants for delivery in Nepal.
AB  - This review is to explore the factors affecting the uptake of skilled birth
      attendants for delivery and the issues associated with women's role and choices
      of maternal health care service for delivery in Nepal. Literature was reviewed
      across the globe and discussed in a Nepalese context. Delivery by Skilled Birth
      Attendance serves as an indicator of progress towards reducing maternal mortality
      worldwide, the fifth Millennium Development Goal. Nepal has committed to reducing
      its maternal mortality by 75% by 2015 through ensuring accessibility to the
      availability and utilisation of skilled care at every birth. The literature
      suggests that several socio-economic, cultural and religious factors play a
      significant role in the use of Skilled Birth Attendance for delivery in Nepal.
      Availability of transportation and distance to the health facility; poor
      infrastructure and lack of services; availability and accessibility of the
      services; cost and convenience; staff shortages and attitudes; gender inequality;
      status of women in society; women's involvement in decision making; and women's
      autonomy and place of residence are significant contributing factors for uptake
      of Skilled Birth Attendance for delivery in Nepal. The review found more
      quantitative research studies exploring the determinants of utilisation of the
      maternal health services during pregnancy in Nepal than qualitative studies.
      Findings of quantitative research show that different social demographic,
      economic, socio-cultural and religious factors are responsible for the
      utilisation of maternal health services but very few studies discussed how and
      why these factors are responsible for utilisation of skilled birth attendants in
      pregnancy. It is suggested that there is need for more qualitative research to
      explore the women's role and choice regarding use of skilled birth attendants
      services and to find out how and why these factors are responsible for
      utilisation of skilled birth attendants for delivery. Qualitative research will
      help further exploration of the issues and contribute to improvement of maternal
      health services.

PMID- 22610740
TI  - Metabolic disease in Nepal: a perspective.
AB  - Inborn errors of metabolism or metabolic diseases, are a group of genetically
      determined metabolic disorders that result in mental retardation or early death.
      The prevalence of IEM in various countries shows a prevalence varying between 1
      in 800 to 1 in 5000. As the technology for detecting metabolites has become more
      advanced, studies utilizing more modern methods report a higher prevalence. There
      have been reports of a few Inborn errors of metabolisms in Nepal, but studies to
      gauge the prevalence of these disorders in the Nepalese population are lacking.
      With conflicting statistical numbers from different sources regarding mental
      retardation cases in Nepalese population and a substantial rate of consanguinity
      and inter caste marriages, it would be prudent to initiate some pilot studies to
      estimate the prevalence of a group of disorders that can be diagnosed through
      simple laboratory tests, to be followed by a screening programme depending upon
      the results. The presented review discusses the need for and the possibilities of
      screening for these errors for early intervention in Nepal.

PMID- 22610741
TI  - Revitalizing primary health care--another utopian goal?
AB  - The quest for greater efficiency, fairness and responsiveness to the expectation
      of the people that system serve have brought about three generations of health
      system reforms in the twentieth century. The first generation saw the founding of
      national health care systems and extension to middle income nations of social
      insurance systems in the 1940s and 1950s. By the late 1960s the rising costs of
      hospital based care, its usage by better off, inaccessibility by the poor and
      rural population of even the most basic services heralded second generation
      reforms promoting primary health care as a means of achieving the affordable
      universal coverage. It included the best public health strategy that is
      prevention and the highest ethical principle of public health that is equity. It
      was expected the best system for reaching households with essential and
      affordable care, and the best route towards universal coverage. The primary
      health care approach though adopted universally did not materialize its notion of
      translating ethos of Health for All by 2000. Overall, primary health care
      movement by the end of 20th century became lifeless. Since the Declaration of
      Alma-Ata, fundamental changes have occurred affecting health service delivery,
      such as economic development and financing approaches, globalization of trade and
      knowledge, and the shift to privatization. This is the time to develop a new
      vision, taking into consideration the many changes affecting global health and
      the strategic developments in health of recent years. With this recognition, the
      third generation of reforms now underway in many countries is driven by the idea
      of responding more to demand, assuring access for the poor and emphasizing
      financing rather than just provision within the public sector. The key concern
      is: how to translate ethos of revitalizing in the reality. Otherwise the
      revitalizing concept will turn into utopian goal so like HFA by 2000 strategy.

PMID- 22610742
TI  - Pseudomembranous colitis in a pregnant woman.
AB  - Pseudomembranous colitis in association with pregnancy has not been well
      described in English literature. Recent studies show a drastic increase in the
      incidence and severity of Pseudomembranous colitis in pregnant women, who were
      once thought to be at low risk. We report here a case of Pseudomembranous colitis
      in a young healthy immunocompetent pregnant lady. An early suspicion of this
      entity with the characteristic appearance of pseudomembranes on colonoscopy and
      histology confirmed the diagnosis enabling prompt treatment and complete recovery
      without any serious consequences.

PMID- 22610743
TI  - Schwartz-Jampel syndrome.
AB  - This is a report of a very rare case of Schwartz Jampel syndrome, with few
      unusual findings, in a 13 years girl from Nepal, who concurrently also had
      superotemporal subluxation of the crystalline lens along with blepharophimosis
      syndrome.

PMID- 22610744
TI  - Tubercular scleritis.
AB  - Scleritis is a severe painful inflammatory process centred in the sclera. A
      scleritis may be a harbinger of many systemic diseases so that it is important to
      exclude multisystem disease. We describe a case of unilateral tubercular anterior
      nodular non-necrotizing scleritis. Anterior nodular non-necrotizing scleritis is
      relatively an uncommon manifestation of tuberculosis. It may be difficult to
      diagnose and manage the disease. However, good history, detail clinical
      evaluation, appropriate and timely management shows a good response to the
      disease.

PMID- 22610745
TI  - Liver sinusoidal endothelial cells contribute to CD8 T cell tolerance toward
      circulating carcinoembryonic antigen in mice.
AB  - Immunity against cancer is impeded by local mechanisms promoting development of
      tumor-specific T cell tolerance, such as regulatory T cells, myeloid-derived
      suppressor cells, or immunosuppressive factors in the tumor microenvironment. The
      release of soluble antigens, such as carcinoembryonic antigen (CEA) from
      colorectal carcinoma (CRC) cells, has been investigated for diagnostic purposes,
      but not for its immunological consequences. Here, we address the question of
      whether soluble CEA influences tumor-specific immunity. Mice were injected with
      soluble CEA protein, and CEA-specific CD8 T cells were analyzed for their
      phenotype and functionality by means of restimulation ex vivo or antitumor
      efficacy in vivo. We furthermore characterized the CD8 T cell population in
      peripheral blood mononuclear cell (PBMCs) from healthy donors and colorectal
      carcinoma patients. In mice, circulating CEA was preferentially taken up in a
      mannose receptor-dependent manner and cross-presented by liver sinusoidal
      endothelial cells, but not dendritic cells, to CD8 T cells. Such systemically
      circulating CEA promoted tolerization of CEA-specific CD8 T cells in the
      endogenous T cell repertoire through the coinhibitory molecule B7H1. These CD8 T
      cells were not deleted but were rendered nonresponsive to antigen-specific
      stimulation and failed to control growth of CEA-expressing tumor cells. These
      nonresponsive CD8 T cells were phenotypically similar to central memory T cells
      being CD44(high) CD62L(high) CD25(neg) . We found T cells with a similar
      phenotype in PBMCs of healthy donors and at increased frequency also in patients
      with colorectal carcinoma. CONCLUSION: Our results provide evidence for the
      existence of an unrecognized tumor immune escape involving cross-presentation of
      systemically circulating tumor antigens that may influence immunotherapy of
      cancer.

PMID- 22610746
TI  - Emerging adults' stress and health: the role of parent behaviors and cognitions.
AB  - Although parent behaviors and cognitions are important for stress/health outcomes
      throughout development, little research examines whether cognitions mediate the
      relationship between parent behaviors and stress/health outcomes. As a result,
      the current study examined the reports of 160 emerging adults regarding their
      mothers' and fathers' behaviors (via the Parental Bonding Instrument and Alabama
      Parenting Questionnaire), their cognitions (via the Stress Appraisal Measure,
      Negative Mood Regulation Scale, Life Orientation Test-Revised, General Self
      Efficacy Scale, and Ruminative Response Scale-Abbreviated), and their
      stress/health outcomes (via the Perceived Stress Scale and Short-Form Health
      Survey). Results of this study suggested that emerging adults' cognitions
      partially mediated the relationship between their mothers' behaviors and their
      stress/health outcomes and fully mediated the relationship between their fathers'
      behaviors and their stress/health outcomes. Future research should examine parent
      behaviors as important distal variables in emerging adults' stress/health
      outcomes but should examine cognitions as more salient, immediate predictors of
      their stress/health outcomes.

PMID- 22610747
TI  - Chemerin: a potential endocrine link between obesity and type 2 diabetes.
AB  - Obesity and type 2 diabetes have reached epidemic levels and account for a
      substantial portion of the annual health expenditures of developed nations. While
      there is an abundance of epidemiological evidence demonstrating that obesity is a
      primary risk factor for developing type 2 diabetes, the mechanism(s) underlying
      this linkage are not completely understood. Given the enormous impact of these
      disorders on global health, considerable research effort has been devoted to
      elucidate the pathophysiological relationship between these two disorders. Two
      factors believed to contribute to the causal link between obesity and type 2
      diabetes are chronic inflammation and altered secretion of adipose-derived
      signaling molecules (adipokines). Independent lines of investigation have
      implicated the novel adipokine chemerin as a regulator of adipogenesis,
      inflammation, and glucose metabolism through interactions with the cognate cell
      surface receptor chemokine-like receptor 1. Increased levels of chemerin that
      occur with obesity are hypothesized to be a causal factor in the development of
      type 2 diabetes as a consequence of dysregulation of the key physiological
      processes regulated by this adipokine. This review summarizes current research on
      the biological roles of chemerin and chemokine-like receptor 1, and highlights
      key questions to guide future research on the role of this adipokine in mediating
      obesity and the development of type 2 diabetes.

PMID- 22610750
TI  - The science of opinion: survey methods in research.

PMID- 22610748
TI  - Improvement of liver function in humans using a mixture of schisandra fruit
      extract and sesamin.
AB  - This was a randomized, parallel, and placebo-controlled study. Forty subjects
      were divided into a test group and a placebo group. The study was focused on the
      potential effects of a mixture of Schisandra fruit extract and sesamin
      (hereinafter called 'SCH') in the subjects with borderline high levels (40-60
      U/L) of alanine aminotransferase (ALT) or aspartate aminotransferase (AST).
      Twenty subjects taking SCH (four tablets per day) and 20 subjects taking a
      placebo (four tablets per day) were studied. The effects of SCH on ALT, AST,
      total bilirubin, direct bilirubin, free radical levels, total antioxidant status,
      glutathione peroxidase, glutathione reductase, and the lag time for low-density
      lipoprotein oxidation were determined. The total test period was 5 months.
      Intervention of SCH clearly reduced the levels of ALT and AST, but it made no
      change in the total bilirubin and direct bilirubin. Intake of SCH also greatly
      increased the antioxidant capacity and decreased the values of thiobarbituric
      acid reactive substances, total free radicals, and superoxide anion radicals in
      the plasma. The activities of glutathione peroxidase and reductase in the
      erythrocytes were significantly increased. In addition, the lag time for low
      density lipoprotein oxidation, an inflammatory marker, was evidently increased.
      Fatty liver was found to have been significantly improved in this study. SCH
      proved to have the effects of antioxidation and improving liver function.

PMID- 22610751
TI  - How much esmolol was administered?

PMID- 22610752
TI  - Yesterday's luxury - today's necessity: end-tidal CO(2) monitoring during
      conscious sedation.

PMID- 22610755
TI  - Interleukin-8 (CXCL8) in tumor associated non-vascular extracellular fluids: its
      diagnostic and prognostic values. A review.
AB  - Interleukin-8 (IL-8, CXCL8) was originally discovered as a powerful attractor and
      activator of polymorphonuclear leukocytes. It was soon recognized that IL-8 also
      affects proliferation and migration of cancer cells, tumor angiogenesis and
      metastasis, and that it is expressed in many cancerous cell types. IL-8 protein
      expression is usually increased in serum of cancer patients, but markedly higher
      concentrations are found in cancer-associated non-vascular extracellular fluids,
      such as pleural effusion, ascites and cyst fluid. Elevated concentrations of IL-8
      are indicative of malignant processes also in cerebrospinal fluid, urine, saliva,
      interstitial fluid and cervicovaginal secretions. Higher IL-8 levels are
      typically found in high-grade peritumoral fluids rather than low-grade tumors and
      benign conditions, with the exception of inflammatory processes. In line with
      recent molecular biology investigations, it appears that the local IL-8
      production is related to its malignant origin and to tumor progression. Hence, IL
      8 in peritumoral fluid is to be taken into consideration while assessing tumor
      character and monitoring the tumor progression/remission status. Besides, the
      data here collected justify the attempts to find an IL-8-targeted inhibitory
      therapy

PMID- 22610754
TI  - High preoperative plasma fibrinogen is an independent predictor of distant
      metastasis and poor prognosis in renal cell carcinoma.
AB  - BACKGROUND: We aimed to evaluate the association of preoperative plasma
      fibrinogen levels with the clinicopathological parameters, disease-free survival,
      and overall survival in patients with renal cell carcinoma. METHODS: We
      retrospectively studied 286 patients with renal cell carcinoma who underwent
      radical nephrectomy from 2000 to 2003 at one center. The plasma fibrinogen was
      routinely determined before operation in all patients. The correlation of
      preoperative plasma fibrinogen levels with clinicopathological findings was
      evaluated by t-test or analysis of variance (ANOVA) methods. As well, univariate
      and multivariate analyses were used to determine the association between the
      preoperative level of plasma fibrinogen and survival duration. RESULTS: An
      elevated level of plasma fibrinogen was positively related to the Fuhrman grade
      (P < 0.001), tumor size (P < 0.001), and T stage (P < 0.001), but it was
      negatively related to histologic type (P = 0.266). Univariate analysis showed
      that the Fuhrman grade, tumor size, T stage, hemoglobin, corrected calcium,
      lactate dehydrogenase, and plasma fibrinogen level were significantly correlated
      with disease-free survival (P < 0.001, P < 0.001, P < 0.001, P < 0.001, P =
      0.001, P < 0.001, and P < 0.001, respectively) and overall survival (P < 0.001, P
      = 0.001, P < 0.001, P < 0.001, P = 0.002, P = 0.001, and P < 0.001). Multivariate
      analysis showed that the plasma fibrinogen level remained as an independent
      prognostic factor for disease-free survival (P = 0.021) and overall survival (P <
      0.001). CONCLUSIONS: A high preoperative plasma fibrinogen level is an
      independent predictor of distant metastasis and survival prognosis after radical
      nephrectomy in patients with renal cell carcinoma.

PMID- 22610753
TI  - Meat and fish consumption and risk of pancreatic cancer: results from the
      European Prospective Investigation into Cancer and Nutrition.
AB  - Pancreatic cancer is the fourth most common cause of cancer death worldwide with
      large geographical variation, which implies the contribution of diet and
      lifestyle in its etiology. We examined the association of meat and fish
      consumption with risk of pancreatic cancer in the European Prospective
      Investigation into Cancer and Nutrition (EPIC). A total of 477,202 EPIC
      participants from 10 European countries recruited between 1992 and 2000 were
      included in our analysis. Until 2008, 865 nonendocrine pancreatic cancer cases
      have been observed. Calibrated relative risks (RRs) and 95% confidence intervals
      (CIs) were computed using multivariable-adjusted Cox hazard regression models.
      The consumption of red meat (RR per 50 g increase per day = 1.03, 95% CI = 0.93
      1.14) and processed meat (RR per 50 g increase per day = 0.93, 95% CI = 0.71
      1.23) were not associated with an increased pancreatic cancer risk. Poultry
      consumption tended to be associated with an increased pancreatic cancer risk (RR
      per 50 g increase per day = 1.72, 95% CI = 1.04-2.84); however, there was no
      association with fish consumption (RR per 50 g increase per day = 1.22, 95% CI =
      0.92-1.62). Our results do not support the conclusion of the World Cancer
      Research Fund that red or processed meat consumption may possibly increase the
      risk of pancreatic cancer. The positive association of poultry consumption with
      pancreatic cancer might be a chance finding as it contradicts most previous
      findings.

PMID- 22610756
TI  - Evaluation of plasma annexin V levels in children and young adults with solid
      tumors.

PMID- 22610757
TI  - Asklepian dreaming and the spirit of transformational healing: linking the
      placebo response to therapeutic uses of self.
AB  - Asklepian medicine - as an archetype of healing - was underpinned by therapeutic
      uses of self, which, if understood, could be beneficial to modern healthcare. It
      is being proposed in this article that therapeutic uses of self from
      instrumental, authentic and transpersonal perspectives could support the process
      of endogenous healing. Such therapeutic uses of self could play a pivotal role in
      activating and enhancing the potential for placebo responses, with spiritual
      significance.

PMID- 22610758
TI  - Effects of a brief psychoanalytic intervention for perinatal depression.
AB  - This pilot study explores the effects of a brief individual psychoanalytic
      therapy on perinatal depressive symptoms. This intervention is based on the
      Geneva's mother-infant intervention model. A sample of 129 pregnant women was
      recruited in Geneva (Switzerland) and screened for depressive symptoms with two
      instruments: the 'Edinburgh postnatal depression scale' (EPDS) and the 'Depistage
      antenatal de la depression postnatale'. A group of 40 women presenting depressive
      symptoms (treatment group) participated in a four-session intervention called
      'Psychotherapy centred on parenthood (PCP)'. It consists in two antenatal and two
      postnatal sessions and is focussed on changing problematic representations of
      parenthood. This treatment group was compared to a control group of 88 women
      without depressive symptoms and following the usual obstetrical care. The main
      outcome measure was EPDS at 3 and 6 months after delivery. The 'Global assessment
      functioning scale' was administered at the end of each therapeutic session. The
      'Parent-infant relationship global assessment scale' was administered at the two
      postnatal sessions in order to explore if PCP was also effective in preventing
      the potential negative effects of depression on mother-infant relationship.
      Results show that in the treatment group (N = 31), EPDS scores dropped from 12.8
      to 4.8; none of these women met the EPDS cut-off score of 12 at 3 and 6 months
      postpartum. Mother-infant relationship was well adapted for all 31 dyads at the
      end of the intervention. These results suggest that PCP is a promising
      intervention for treating perinatal depression and helping mothers engaging in
      parenting.

PMID- 22610760
TI  - Childhood obesity, unrecognised public health challenge in Nepal.

PMID- 22610761
TI  - Positive mental health need for holistic approach.

PMID- 22610759
TI  - A latent modeling approach to genotype-phenotype relationships: maternal problem
      behavior clusters, prenatal smoking, and MAOA genotype.
AB  - This study illustrates the application of a latent modeling approach to genotype
      phenotype relationships and gene * environment interactions, using a novel,
      multidimensional model of adult female problem behavior, including maternal
      prenatal smoking. The gene of interest is the monoamine oxidase A (MAOA) gene
      which has been well studied in relation to antisocial behavior. Participants were
      adult women (N = 192) who were sampled from a prospective pregnancy cohort of non
      Hispanic, white individuals recruited from a neighborhood health clinic.
      Structural equation modeling was used to model a female problem behavior
      phenotype, which included conduct problems, substance use, impulsive-sensation
      seeking, interpersonal aggression, and prenatal smoking. All of the female
      problem behavior dimensions clustered together strongly, with the exception of
      prenatal smoking. A main effect of MAOA genotype and a MAOA * physical
      maltreatment interaction were detected with the Conduct Problems factor. Our
      phenotypic model showed that prenatal smoking is not simply a marker of other
      maternal problem behaviors. The risk variant in the MAOA main effect and
      interaction analyses was the high activity MAOA genotype, which is discrepant
      from consensus findings in male samples. This result contributes to an emerging
      literature on sex-specific interaction effects for MAOA.

PMID- 22610762
TI  - Refractive errors and visual anomalies in school children in the Kavrepalanchowk
      District.
AB  - BACKGROUND: Schoolchildren form an important target group for a nation, as any
      ocular morbidity in this age group has huge physical, psychological and socio
      economical implications. Childhood eye disorders can contribute to the burden of
      blindness in any society. This study aims to highlight the prevalence of ocular
      morbidity in governmental schools in a sub-urbanised area of Nepal, in relation
      to ethnic variation. METHODS: A descriptive study, and the study population used
      were schoolchildren who were examined in their schools and afterwards referred to
      the hospital if required. Presenting and best corrected visual acuity,
      refraction, binocularity assessment, anterior and posterior segment evaluation
      was carried out. Data was analysed statistically using SPSS software, version 14.
      RESULTS: We examined 1,802 school children. The mean age was 10.78 +/- 3.61
      years. Ocular abnormality was detected in 11.7%. Low vision and blindness was
      rare (0.11% and 0.05%). Ocular morbidities were more common in Newar communities
      (3.71%) followed by Brahamans (3.38%). Lid abnormalities were the most common
      (3.55%), and morbidities in each ethnicity were followed by refractive errors
      (3%), conjunctival abnormalities (1.10%), strabismus (0.88%) and amblyopia
      (0.33%). Refractive errors were most common among Newar communities (1.16%) at
      almost twice as many Brahamans (0.61%) followed by Mongolians (0.49%).
      Convergence insufficiency was detected in 2.49% (p less than 0.01). CONCLUSIONS:
      Ocular morbidities are common in children in Kavhrepalanchowk District with lid
      abnormalities being the most common issue, probably due to a lack of hygienic
      practice. Ethnic variation of ocular morbidities is an important observation
      mostly for refractive error and strabismus.

PMID- 22610765
TI  - Psychiatric illness in the paediatric population presenting to a psychiatry
      clinic in a tertiary care centre.
AB  - BACKGROUND: A variety of psychiatric manifestations can be seen in children below
      the age of 18 years. Such cases rarely present directly to psychiatric care.
      METHODS: Retrospective study in Tertiary care hospital . The study population
      included all the patients of paediatric age group presenting to Psychiatry
      Outpatient Department of Dhulikhel Hospital directly or referred by a
      paediatrician or other specialists from October 2008 to October 2010. RESULTS:
      Among the paediatric population evaluated in the psychiatry clinic for two years
      from October 2008 to October 2010 (N = 168), 66.7% were in the age group 15-18
      years {mean = 14.77 (+/- 2.99)}, 71.4% were female and 42.3% belonged to Brahmin
      cast. The highest number of (15%) patients was seen during the month of August
      2010. Six months analysis of the psychiatric illnesses of the patients from April
      2010 up to October 2010 (n = 80) showed dissociative disorder (15%), and seizure
      disorder (15%) to be the most common diagnoses, followed by depressive disorder
      and intentional self harm (ISH) (13.8% each). 15% of patients were found to be
      treated by magico-religious means, with the majority of patients (66.7%)
      diagnosed as having dissociative disorder. CONCLUSION: The majority of the
      paediatric population presenting to a psychiatry clinic were in the age group 15
      18 years and of female sex. Dissociative disorder was the most common diagnosis
      followed by depressive disorders. The majority of patients with dissociative
      disorder had previously been treated by magico-religious means.

PMID- 22610764
TI  - Reduced vision and refractive errors, results from a school vision screening
      program in Kanchanpur District of far western Nepal.
AB  - BACKGROUND: At present there is no data available on reduced vision and
      refractive errors in school children of far western Nepal. So, school screening
      records were used to obtain data useful for planning of refractive services.
      METHODS: Data are provided from school screening conducted by Geta Eye Hospital
      during February/March 2008. The cases with complete data sets on visual acuity,
      refractive error and age were included and analyzed using computer software.
      RESULTS: Of 1165 children (mean age 11.6 +/- 2.5 years) examined, 98.8% (n =
      1151) had uncorrected visual acuity of 6/9 and better in at least one eye whereas
      1.2% (n = 14) had acuity 6/12 and worse in both eyes. Among them, either eye of 9
      children improved to 6/9 and better with correction. However, visual acuity was
      6/12 and worse in both eyes of 5 children even after correction. There were 24
      children with refractive errors (myopia, 1.54%; n = 18 and hypermetropia, 0.51%;
      n = 6) in at least one eye. The spherical equivalent refraction was not
      significantly different with age and gender. CONCLUSIONS: The incidence of
      reduced vision and refractive errors among school children of this semi rural
      district were low.

PMID- 22610763
TI  - Laparoscopic cholecystectomy complication and conversion rate.
AB  - BACKGROUND: Laparoscopic cholecystectomy has become standard method for treating
      gallstone. However, different centres have reported different complications and
      conversion rate. The objective of this study was to evaluate complications and
      conversion of laparoscopic cholecystectomy into open cholecystectomy in Dhulikhel
      Hospital, Kathmandu University, Nepal. METHODS: Files of all patients who had
      laparoscopic cholecystectomy from January 2005 to December 2009 were reviewed.
      Out of 119 laparoscopic cholecystectomy cases, 102 were included in the study as
      complete information was lacking in the rest. RESULTS: Out of 102 cases, 80 were
      female. Symptomatic cholelithiasis were 76.47%. The mean hospital stay was 2.48
      days. Postoperative complications occurred in 5.88% patients. Conversion rate to
      open cholecystectomy was 3.92%. CONCLUSIONS: Laparoscopic cholecystectomy is a
      reliable and safe surgery. With growing experience in laparoscopic technique, it
      is possible to bring complications and conversion rate to minimum. However, there
      will be no significant improvements once learning curve is reached. Rather, the
      nature of biliary injury may become more severe.

PMID- 22610766
TI  - Evaluation of lipid peroxidation and antioxidants' status in metabolic syndrome.
AB  - BACKGROUND: Metabolic syndrome is a constellation of physical conditions and
      metabolic abnormalities, commonly occurring together, that increases an
      individual's risk for development of type 2 diabetes mellitus and cardiovascular
      diseases. Oxidative stress is associated with diabetes, hypertension and other
      cardiovascular diseases while the role of oxidative stress in pathogenesis of MS
      is not clearly defined. OBJECTIVES: The study aims to find out the prevalence of
      metabolic syndrome in faculty and staff members at BP Koirala Institute of Health
      Sciences, Dharan, Nepal and to evaluate oxidative stress levels in subjects with
      metabolic syndrome. METHODS: 118 healthy participants working at B. P. Koirala
      Institute of Health Sciences, Dharan, Nepal were selected at random for this
      cross-sectional study and blood samples were collected for the estimation of the
      following biochemical analytes; fasting glucose; triglycerides; total
      cholesterol; high density lipoprotein cholesterol; Albumin; uric acid; Bilirubin;
      Malondialdehyde; Catalase; Glutathione peroxidase; Superoxide Dismutase;
      Glutathione; vitamin C; and lastly vitamin E. Results In this cross-sectional
      study, 39% subjects were diagnosed with metabolic syndrome , particularly in
      sedentary subjects. There was no difference in oxidative stress except
      significant rises in serum uric acid levels and catalase activity in subjects
      diagnosed with metabolic syndrome . CONCLUSION: The prevalence of metabolic
      syndrome is higher without oxidative stress in this study, which suggests that
      oxidative stress does not contribute to the pathogenesis of MS in otherwise
      healthy subjects.

PMID- 22610767
TI  - Comparison of clinical presentation between Chronic Otitis Media Mucosal with
      Squamous.
AB  - BACKGROUND: Chronic otitis media is a chronic inflammatory disease of the middle
      ear cleft which is manifested as deafness and ear discharge. It is a common
      condition affecting 0.5 - 30% of any community worldwide, and most common in
      developing countries. The prevalence mainly depends on age, low socio-economic
      status, overcrowding and limited medical facilities. OBJECTIVE: To compare the
      clinical presentation between chronic otitis media mucosal with squamous types.
      METHODS: A prospective, longitudinal and analytical study performed among 200
      patients who have features of chronic otitis media and were attended to in the
      ear, nose and throat outpatient department of Dhulikhel Hospital - Kathmandu
      University Hospital, Dhulikhel, Nepal from January 2010 to January 2011. Patients
      who had already undergone surgery and came back to the hospital, with inadequate
      information were excluded from the study. RESULTS: The results showed that, out
      of 200 cases, 120 (60%) were chronic otitis media- mucosal and 80 (40%) were
      chronic otitis media - squamous. Patients less than 30 years were affected in
      both groups. The male to female ratio in chronic otitis media mucosal was 1.14:1,
      whereas in chronic otitis media squamous, it was 1.96:1. Similarly in etiological
      factors, oil and water exposure (76%) was the most common cause in chronic otitis
      media mucosal, whereas in chronic otitis media squamous, oil and water exposure
      (62.5%) and recurrent upper respiratory tract infection (62.5%) were the most
      common causes. Of all the clinical features, ear discharge was the leading
      feature in both chronic otitis media mucosal (98%) and squamous (100%) cases. The
      complications were mainly seen in the chronic otitis media squamous and the most
      common complication was mastoid abscess (5%). CONCLUSIONS: The frequency of
      chronic otitis media is higher in the younger age group and those lacking in
      health education. As a result, it is important to disseminate the health
      education regarding the ear disease which will help in decreasing the frequency
      of the disease in developing countries like ours.

PMID- 22610768
TI  - Risk factors of multidrug resistant tuberculosis in central Nepal: a pilot study.
AB  - INTRODUCTION: Tuberculosis is the most widespread infectious disease in Nepal and
      poses a serious threat to the health and development of the country. Incidences
      of drug resistant tuberculosis in Nepal are increasing and this tuberculosis a
      major threat to successfully controlling tuberculosis. OBJECTIVE: The general
      objective of the study was to assess the risk factors of multi-drug resistant
      tuberculosis among the patients attending the National Tuberculosis Centre,
      Bhaktpur Nepal. METHODS: An observational study/ case-control study with a total
      number of 55 multi-drug resistant tuberculosis cases and 55 controls. The study
      was conducted among the patient attending in the National Tuberculosis Centre,
      Bhaktpur Nepal for six months, between May-October 2010. sImulti-drug resistant
      tuberculosis wasThe collected data was analysed in SPSS 11.5 version. The
      association between categorical variables were analysed by chi-square tests, OR
      and their 95% CI were measured. RESULTS: The total number of patients used for
      the study was 110, of which among them 55 were cases and 55 were controls . Our
      study revealed that there were significant associations between history of prior
      TB MDR-TB OR = 2.799 (95 % CI 1.159 to 6.667) (p = 0.020); smoking habit OR =
      2.350 and (95%CI 1.071 to 5.159) (p = 0.032); social stigma social stigma OR
      2.655 (95%CI r 1.071 to 5.159) (p = 0.013); knowledge on MDR-TB OR = 9.643 (95%
      CI 3.339 to 27.846) (p less than 0.001)and knowledge on DOTS Plus OR = 16.714
      (95% CI is ranging from 4.656 to 60.008) (p less than 0.001). However, there was
      no association found between alcohol drinking habits and ventilation in the room.
      CONCLUSION: Our study revealed that there were significant associations between
      history of prior tuberculosis, smoking habit social stigma social stigma,
      knowledge on multi-drug resistant tuberculosis and knowledge on DOTS Plus with
      multi-drug resistant tuberculosis However there was no association between
      alcohol drinking habit and ventilation in room with multi-drug resistant
      tuberculosis.

PMID- 22610769
TI  - Evaluation of non-HDL-c and total cholesterol: HDL-c ratio as cumulative marker
      of cardiovascular risk in diabetes mellitus.
AB  - BACKGROUND: Cardiovascular disease (CVD), is the primary cause of morbidity and
      mortality in patients with diabetes and have approximately--two to four times
      higher CVD rate than adult without diabetes. Low density lipoprotein cholesterol
      (LDL-C) is primarily used as the marker of cardiovascular risk in diabetes
      despite its several limitations. Although several newer markers of CVD are
      emerging, no marker has been established in Nepal. OBJECTIVES: The study was
      designed to evaluate the non-high-density-lipoprotein- cholesterol(Non-HDL-C) and
      Total Cholesterol to High density lipoprotein cholesterol (TC:HDL-C ratio) as CVD
      risk marker in diabetes mellitus. METHODS: The study was conducted in the
      Department of Biochemistry, Kathmandu University School of Medical Sciences. The
      study comprised of 76 diabetic subjects and 60 non-diabetic subjects. The
      anthropometric and biochemical parameters were measured. The Non-HDL-C and TC:HDL
      C ratio were also calculated employing their respective formula. RESULTS: Body
      mass index (BMI), waist circumference (WC), blood pressure and lipid parameters
      were significantly different between diabetic subjects and non-diabetic subjects.
      There was increased non-HDL-C and TC:HDL-C ratio in subjects with diabetes
      mellitus. Furthermore, statistically significant correlations of non-HDL-C and
      TC:HDL-C ratio were obtained with BMI, WC, total cholesterol, HDL-C and LDL-C in
      diabetic subjects. CONCLUSIONS: The present study observation revealed that the
      Non-HDL-C and TC: HDL-C strongly correlate with established independent risk
      factors such as obesity(WC), elevated blood pressure, HDL-C and LDL-C in
      diabetes. Thus, the evaluation of Non-HDL-C and TC: HDL-C ratio can be used as
      the simple, cost-effective and cumulative marker of cardiovascular risk in
      diabetes mellitus.

PMID- 22610770
TI  - Phonatory vocal tract stability in stuttering children before and after fluency-
      enhancing therapy.
AB  - BACKGROUND: Stuttering is a complex disorder. Essentially, it is a neuromuscular
      disorder whose core consists of tiny lags and disruptions in the timing of the
      complicated movements required for speech. OBJECTIVE: The purpose of the current
      study was to collec and comparg jitters and shimmer values in children who
      stutter before and after fluency--enhancing therapy. METHODS: Subjects consisted
      of 15 Iranian preschool girls with stutterg, and 15 Iranial preschool girls
      without afflictions, matched according to age. Vocal jittering and shimmer
      measurements of thesphonation of the children were compared before and after
      therapy. Each subject phonated vowels nine times in a random order. Each
      phonation was sustained for at least five seconds and was recorded. The middle
      three-second portion of each recorded vowel phonation was subjected to jitter and
      shimmer analysis. RESULTS: On shimmer measures between pre-treatment and post
      treatment, significant differences were found in all sustained vowels of persons
      who stutter group and means of shimmer in post therapy were significantly lower
      than pre-treatment. Differences in jitter measurements were not significant
      between pre-treatment and post-treatment statuses and this parameter did not
      change after therapy. CONCLUSION: The findings showed that therapy resulted in
      decreaseg irregularity in the amplitude of vibrations (shimmer). In other words,
      the therapy increases the steady-state of the laryngeal system. Moreover, this
      parameter may be used as an index for the effectiveness of therapy.

PMID- 22610771
TI  - Incidence of simian crease in normal Nepalese children.
AB  - BACKGROUND: Simian crease is usually associated with some chromosomal anomalies
      and syndromes but it is also seen in some populations without any chromosomal
      defects. OBJECTIVE: To see the incidence of simian crease in children without
      chromosomal anomalies and to detect the Ethnic group variations. METHODS: A
      prospective study in children attending the paediatric outpatient department of
      Manipal Teaching Hospital, Pokhara. 2,067 children were screened randomly from
      the 1st June 2007 to the 31st December 2007. Palm crease and axial triradius
      angle were detected in every child. Axial Triradius angle was compared between
      those who have simian crease to those who do not simian crease. Children who were
      found with simian crease underwent IQ testing. The exclusion criteria were
      children with Down syndrome, other chromosomal and minor anomalies, plus or any
      other chronic disease condition. RESULTS: Two thousand sixty seven children
      (1,084 boys and 983 girls) were screened. Among them four were cases of Down
      syndrome so were excluded from the study. Finally total of 2,063 (1,082 boys and
      981 girls) were the study group. There were a total 14 ethnic groups who attended
      the outpatient department of Manipal Hospital during a seven months period. Among
      the seven ethnic groups Brahaman, Gurung, Tamang, Lama, Newar, Chettri and Dalit
      had single palmar crease. The incidence of simian crease was 14.6%.This incidence
      was highly significant (p less than 0001) in Lama population (71.2%). In these
      seven ethnic groups axial triradius angle was compared between those who had
      simian crease and with those who did not have simian crease. Comparisons were
      made statistically and found to be significant. CONCLUSION: Incidence of simian
      crease in Nepalese children was 14.6% and was observed only in certain ethnic
      groups. It was significantly high in the Lama population (71.2%).

PMID- 22610772
TI  - Prevention of hypotension following spinal anaesthesia in caesarean section--then
      and now.
AB  - Hypotension during spinal anaesthesia for caesarean section remains a common
      scenario in our clinical practice. Certain risk factors play a role in altering
      the incidence of hypotension. Aortocaval compression counteraction does not help
      to prevent hypotension. Intravenous crystalloid prehydration has poor efficacy;
      thus, the focus has changed toward co-hydration and use of colloids.
      Phenylephrine is established as a firstline vasopressor, although there are
      limited data from high-risk patients. Ephedrine crosses the placenta more than
      phenylephrine and cause possible alterations in the foetal physiology.

PMID- 22610773
TI  - Unusual site of metastasis of bronchogenic carcinoma.
AB  - Metastasis of bronchogenic carcinoma to the chest wall and axillary lymphnodes is
      a rare occurrence. This study reports the case of a patient presenting with chest
      wall swelling as initial symptom which on evaluation was found to be a lymphnode
      metastasis. The patient also had axillary lymphnode metastasis on the same side
      as the chest swelling with a contralateral pleural effusion. Here, we discuss the
      pathways and possible mechanisms of contra lateral axillary and chest wall
      lymphnode involvement without ispilateral nodal involvement in bronchogenic
      carcinoma.

PMID- 22610774
TI  - Branch retinal arterial occlusion.
AB  - Retinal arterial occlusion is an ocular emergency in which visual prognosis is
      poor mostly due to late presentation of the patient and macular involvement. The
      casee described, in this report is ane incidence of Branch Retinal Arterial
      Occlusion in a 22 year old female with grade II Mitral Regurgitation. The
      patiente presented witha complaint of painless, diminution of vision in the right
      eyn. She also presented with perception of black shadow in the superior visual
      fiel n of the same eye5 for five days. There was no significant systemic ord
      personal history. Her visual acuity at presentation was 6/60 and 6/6 in the right
      and left eyes,y which did not improve with glasses or pin-hole. Anterior segment
      including papillary reaction was normal in both eyes while Fundus examination of
      the right eye revealed retinal whitening inside the inferotemporal vascular
      arcade that was encroaching foveolar avascular zone. Visual field defect was
      detected at superonasally inside arhade but Fundus Fluorescence Angiography was
      normal. An echoycardiograph revealed grade II Mitral Regurgitation. The patient
      was kept on observation and after two2 days of follow-up, vision in the right eye
      was improved to 6/6 unaided but visual field defect was remained same.

PMID- 22610775
TI  - Neonatal abstinence syndrome.
AB  - Intrauterine exposure to drugs by mothers is not an uncommon finding ine our
      society. Due to the mother's suppression of a medical history, the diagnosis of
      neonatal abstinence syndrome is often missed. We report a case of a term, female,
      newborn, who presented with the following features;e restlessness, inconsolable
      crying, along with sweating, vigorous sucking; andadiarrhoea. No conclusion was
      derived from routine investigations. Eventually, with a high degree of suspicion
      regarding maternal drug addiction, her history was reviewed and it was discovered
      that the mother was a heroin addict. The baby was diagnosed as a case of Neonatal
      Abstinence Syndrome. The neonate was successfully managed thereafter and
      discharged.

PMID- 22610776
TI  - Anomalous superior thyroid artery.
AB  - The variations in the pattern of distribution of superior thyroid artery assume
      paramount importance for neck surgeons, in view of its vital topographical
      relationship to the external laryngeal nerve. In this study, we report an unusual
      variation in the arterial supply of the thyroid gland, which was detected during
      a routine dissection of an adult male cadaver. The right superior thyroid artery
      was absent whereas the left superior thyroid artery took origin from the left
      common carotid artery and showed a dominant pattern of distribution supplying the
      superior aspect of both the left and right lobes of the thyroid gland. It
      exhibited a usual relationship with the left external laryngeal nerve. The
      inferior thyroid arteries did not show any unusual distribution. Knowledge of
      such arterial variations related to the thyroid gland is immensely helpful for
      surgeons in order to put ligature on anomalous artery and to avoid damage to
      vital structures in this area, such as the external laryngeal nerve.

PMID- 22610777
TI  - Doubly biomimetic catecholic phosphorylcholine copolymer: a platform strategy for
      fabricating antifouling surfaces.
AB  - A doubly biomimetic PMNC polymer bearing cell antifouling phosphorylcholine and
      mussel adhesive protein catechol groups is synthesized. The polymer can be
      deposited onto a variety of substrates by dip-coating in an aqueous solution,
      adhering to surfaces via the catechol functional group while at the same time
      forming a cell outer membrane mimetic antifouling surface. Contact angle, ATR
      FTIR and XPS measurements confirm polymer coating formation on a variety of
      inorganic and organic substrates. BSA and bovine plasma fibrinogen protein
      adsorption on PMNC coated surfaces are reduced significantly compared to
      unmodified substrates, and platelet adhesion from human serum onto the PMNC
      coated substrate surfaces is highly suppressed in this study.

PMID- 22610778
TI  - Challenges in T cell receptor gene therapy.
AB  - The function of T lymphocytes as orchestrators and effectors of the adaptive
      immune response is directed by the specificity of their T cell receptors (TCRs).
      By transferring into T cells the genes encoding antigen-specific receptors, the
      functional activity of large populations of T cells can be redirected against
      defined targets including virally infected or cancer cells. The potential of
      therapeutic T cells to traffic to sites of disease, to expand and to persist
      after a single treatment remains a major advantage over the currently available
      immunotherapies that use monoclonal antibodies. Here we review recent progress in
      the field of TCR gene therapy, outlining challenges to its successful
      implementation and the strategies being used to overcome them. We detail
      strategies used in the optimization of affinity and surface expression of the
      introduced TCR, the choice of T cell subpopulations for gene transfer, and the
      promotion of persistence of gene-modified T cells in vivo. We review the safety
      concerns surrounding the use of gene-modified T cells in patients, discussing
      emerging solutions to these problems, and describe the increasingly positive
      results from the use of gene-modified T cells in recent clinical trials of
      adoptive cellular immunotherapy. The increasing sophistication of measures to
      ensure the safety of engineered T cells is accompanied by an increasing number of
      clinical trials: these will be essential to guide the effective translation of
      cellular immunotherapy from the laboratory to the bedside.

PMID- 22610779
TI  - A coupled flow-acoustic computational study of bruits from a modeled stenosed
      artery.
AB  - The sound generated by blood flow in stenosed arteries is investigated for a
      model that consists of a channel with a one-sided constriction. The blood flow
      induced arterial "bruits" are computed directly using a hybrid approach wherein
      the hemodynamic flow field is solved by an immersed boundary, incompressible flow
      solver, and the sound generation is modeled by a first-principles approach that
      employs the linearized compressible perturbation equations. The transmission and
      propagation of the sound through the surrounding biological tissues is also
      modeled with a simplified, linear structural wave equation. The flow field inside
      the artery and the bruit sound signal at the epidermal surface are examined to
      delineate the precise source of the arterial bruit and the correlation between
      the bruit and the arterial wall pressure fluctuations. It is found that the
      bruits are related primarily to the time-derivative of the integrated pressure
      force on the post-stenotic segment of arterial wall. The current study provides a
      clear perspective on the generation of bruits from stenosed arteries and enables
      an assessment of the conjectures of previous researchers regarding the source of
      arterial bruits.

PMID- 22610780
TI  - CD44+/CD24- ovarian cancer cells demonstrate cancer stem cell properties and
      correlate to survival.
AB  - Cancer cells with the surface marker profile CD44+/CD24- have previously been
      described to possess cancer stem cell-like properties. This manuscript evaluates
      those properties in ovarian cancer cell lines. The proportion of CD44+/CD24-
      cells corresponded to the clinical aggressiveness of each ovarian cancer cell
      line histologic subtype. CD44+/CD24- cells demonstrated enhanced progressive
      differentiation as well as showing a 60-fold increase in Matrigel invasion in
      both SKOV3 and OV90 cell lines (p < 0.001 each) compared to other phenotypes.
      CD44+/CD24- demonstrated significant resistance to all chemotherapy agents used
      in all cell lines, with a 71-93 % increase in resistance compared with baseline.
      Using a threshold of 25 % CD44+/CD24- ovarian cancer cells found in ascites,
      patients with >25 % CD44+/CD24- were significantly more likely to recur (83 vs.
      14 %, p = 0.003) and had shorter median progression-free survival (6 vs. 18
      months, p = 0.01). In conclusion, the CD44+/CD24- phenotype in ovarian cancer
      cells demonstrate cancer stem cell-like properties of enhanced differentiation,
      invasion, and resistance to chemotherapy. This CD44+/CD24- phenotype correlates
      to clinical endpoints with increased risk of recurrence and shorter progression
      free survival in patients with ovarian cancer.

PMID- 22610781
TI  - Walker 256 tumour cells increase substance P immunoreactivity locally and modify
      the properties of the blood-brain barrier during extravasation and brain
      invasion.
AB  - It is not yet known how tumour cells traverse the blood-brain barrier (BBB) to
      form brain metastases. Substance P (SP) release is a key component of neurogenic
      inflammation which has been recently shown to increase the permeability of the
      BBB following CNS insults, making it a possible candidate as a mediator of tumour
      cell extravasation into the brain. This study investigated the properties of the
      BBB in the early stages of tumour cell invasion into the brain, and the possible
      involvement of SP. Male Wistar rats were injected with Walker 256 breast
      carcinoma cells via the internal carotid artery and euthanised at 1, 3, 6 and 9
      days post tumour inoculation. Culture medium-injected animals served as controls
      at 1 and 9 days. Evidence of tumour cell extravasation across the BBB was first
      observed at 3 days post-inoculation, which corresponded with significantly
      increased albumin (p < 0.05) and SP immunoreactivity (p < 0.01) and significantly
      reduced endothelial barrier antigen labelling of microvessels when compared to
      culture medium control animals (p < 0.001). By day 9 after tumour cell
      inoculation, 100 % of animals developed large intracranial neoplasms that had
      significantly increased albumin in the peri-tumoral area (p < 0.001). The
      increased SP immunoreactivity and altered BBB properties at 3 days post
      inoculation that coincided with early tumour invasion may be indicative of a
      mechanism for tumour cell extravasation into the brain. Thus, extravasation of
      tumour cells into the brain to form cerebral metastases may be a SP-mediated
      process.

PMID- 22610782
TI  - Droxidopa, an oral norepinephrine precursor, improves hemodynamic and renal
      alterations of portal hypertensive rats.
AB  - We aimed to evaluate the effects of droxidopa (an oral synthetic precursor of
      norepinephrine) on the hemodynamic and renal alterations of portal hypertensive
      rats. Sham, portal vein-ligated (PVL), and 4-week biliary duct-ligated (BDL) rats
      received a single oral dose of droxidopa (25-50 mg/kg) or vehicle and hemodynamic
      parameters were monitored for 2 hours. Two groups of BDL and cirrhotic rats
      induced by carbon tetrachloride (CCl(4) ) were treated for 5 days with droxidopa
      (15 mg/kg, twice daily, orally); hemodynamic parameters and blood and urinary
      parameters were assessed. The droxidopa effect on the Rho kinase (RhoK) / protein
      kinase B (AKT) / endothelial nitric oxide synthase (eNOS) pathways was analyzed
      by western blot in superior mesenteric artery (SMA). The acute administration of
      droxidopa in PVL and BDL rats caused a significant and maintained increase in
      arterial pressure and mesenteric arterial resistance, with a significant decrease
      of mesenteric arterial and portal blood flow, without changing portal pressure
      and renal blood flow. Two-hour diuresis greatly increased. Carbidopa (DOPA
      decarboxylase inhibitor) blunted all effects of droxidopa. Chronic droxidopa
      therapy in BDL rats produced the same beneficial hemodynamic effects observed in
      the acute study, did not alter liver function parameters, and caused a 50%
      increase in 24-hour diuresis volume (7.4 +/- 0.9 mL/100g in BDL vehicle versus
      11.8 +/- 2.5 mL/100g in BDL droxidopa; P = 0.01). Droxidopa-treated rats also
      showed a decreased ratio of p-eNOS/eNOS and p-AKT/AKT and increased activity of
      RhoK in SMA. The same chronic treatment in CCl(4) rats caused similar hemodynamic
      effects and produced significant increases in diuresis volume and 24-hour
      natriuresis (0.08 +/- 0.02 mmol/100g in CCl(4) vehicle versus 0.23 +/- 0.03
      mmol/100g in CCl(4) droxidopa; P = 0.014). CONCLUSION: Droxidopa might be an
      effective therapeutic agent for hemodynamic and renal alterations of liver
      cirrhosis and should be tested in cirrhosis patients.

PMID- 22610783
TI  - Conducted electrical weapon incapacitation during a goal-directed task as a
      function of probe spread.
AB  - Despite training and field experience that the location and spread between
      conducted electrical weapon (CEW) probes is important in establishing
      incapacitation, there have been no human studies which have systematically
      examined the relationships between probe spread and incapacitation. We have
      investigated this relationship with the TASER((r)) X26. We have also developed
      and validated methodologies for prospective assessment of the effectiveness of
      CEWs in the incapacitation of highly motivated human subjects. Subjects (n = 30)
      had probes placed on the front or back with randomly varied spreads in accordance
      with recommended targeting zones. Subjects were motivated to complete the task of
      disabling the device or a dummy officer suspended ten feet away during the
      exposure while using a training knife. Subjects were rated on their progress
      toward goal success and on the extent of any incapacitation using two separate
      observer scoring panels: one consisting of experts in physiology and X26
      technology, and another of veteran peace officers. Incapacitation by all measures
      was found to be a function of spread; generally increasing in effectiveness up to
      spreads between 9 and 12 in. There were notable differences between front and
      back exposures, with front exposures not leading to full incapacitation of the
      upper extremities regardless of probe spread. This is the first published study
      on a quantitative methodology for directly assessing the effectiveness of CEWs in
      human incapacitation. We have also validated and quantified for the first time in
      human subjects that establishing a minimal spread between X26 probes correlates
      to the extent of device effectiveness.

PMID- 22610784
TI  - Pharmacokinetic profiling of efavirenz-emtricitabine-tenofovir fixed dose
      combination in pregnant and non-pregnant rats.
AB  - During pregnancy, the disposition of various drugs is altered due to changes in
      physiological condition, maternal gastrointestinal absorption, gastric secretion
      and motility. A fixed dose combination of antiretrovirals is commonly prescribed
      for the treatment of HIV infection. There is a need to understand the
      pharmacokinetics and placental transfer of efavirenz-emtricitabine-tenofovir in
      fixed dose combination during pregnancy. The pharmacokinetics and placental
      transfer of efavirenz-emtricitabine-tenofovir fixed dose combination was
      evaluated in timed pregnant and non-pregnant Sprague-Dawley rats at 30, 10, 15
      mg/kg p.o., respectively. The plasma, placental tissue, amniotic fluid and fetal
      tissue concentrations were measured using high performance liquid chromatography
      combined with tandem mass spectrometric detector (LC-MS/MS). To summarize, the
      pharmacokinetic profile of efavirenz remained similar in the pregnant and non
      pregnant rats. However, a considerable difference in the pharmacokinetics of
      emtricitabine and tenofovir was observed in pregnant and non-pregnant rats.
      Efavirenz and emtricitabine showed appreciable placental, amniotic fluid and
      fetal exposure compared with tenofovir. The present study suggests that a
      profound impact on antiretroviral pharmacokinetics was observed during pregnancy
      and there is a need to monitor the exposure levels of each drug when administered
      as a fixed dose combination during pregnancy. Further studies to explore the
      pharmacokinetic parameters of fixed dose antiretrovirals during the preclinical
      stage in a timed-pregnancy rat model are required. Such studies can help in the
      development of safe and effective medications with a reduced risk of perinatal
      transmission of HIV-1 infection.

PMID- 22610785
TI  - Reciprocal induction between alpha-synuclein and beta-amyloid in adult rat
      neurons.
AB  - In spite of definite roles for beta-amyloid (Abeta) in familial Alzheimer's
      disease (AD), the cause of sporadic AD remains unknown. Amyloid senile plaques
      and Lewy body pathology frequently coexist in neocortical and hippocampal regions
      of AD and Parkinson's diseases. However, the relationship between Abeta and alpha
      synuclein (alpha-Syn), the principle components in the pathological structures,
      in neuronal toxicity and the mechanisms of their interaction are not well
      studied. As Abeta and alpha-Syn accumulate in aging patients, the biological
      functions and toxicity of these polypeptides in the aging brain may be different
      from those in young brain. We examined the neurotoxicity influences of Abeta1-42
      or alpha-Syn on mature neurons and the effects of Abeta1-42 or alpha-Syn on the
      production of endogenous alpha-Syn or Abeta1-40 reciprocally using a model of
      culture enriched with primary neurons from the hippocampus of adult rats.
      Treatment of neurons with high concentrations of Abeta1-42 or alpha-Syn caused
      significant apoptosis of neurons. Following Abeta1-42 treatment at sub apoptotic
      concentrations, both intra- and extra-cellular alpha-Syn levels were
      significantly increased. Reciprocally, the non-toxic levels of alpha-Syn
      treatment also increased intra- and extra-cellular Abeta1-40 levels. The
      phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, suppressed alpha-Syn
      induced Abeta1-40 elevation, as well as Abeta1-42-induced alpha-Syn elevation.
      Thus, high concentrations of Abeta1-42 and alpha-Syn exert toxic effects on
      mature neurons; however, non-toxic concentration treatment of these polypeptides
      induced the production of each other reciprocally with possible involvement of
      PI3K pathway.

PMID- 22610786
TI  - Toxicity of carbon nanotubes to freshwater aquatic invertebrates.
AB  - Carbon nanotubes (CNTs) are hydrophobic in nature and thus tend to accumulate in
      sediments if released into aquatic environments. As part of our overall effort to
      examine the toxicity of carbon-based nanomaterials to sediment-dwelling
      invertebrates, we have evaluated the toxicity of different types of CNTs in 14-d
      water-only exposures to an amphipod (Hyalella azteca), a midge (Chironomus
      dilutus), an oligochaete (Lumbriculus variegatus), and a mussel (Villosa iris) in
      advance of conducting whole-sediment toxicity tests with CNTs. The results of
      these toxicity tests conducted with CNTs added to water showed that 1.00 g/L (dry
      wt) of commercial sources of CNTs significantly reduced the survival or growth of
      the invertebrates. Toxicity was influenced by the type and source of the CNTs, by
      whether the materials were precleaned by acid, by whether sonication was used to
      disperse the materials, and by species of the test organisms. Light and electron
      microscope imaging of the surviving test organisms showed the presence of CNTs in
      the gut as well as on the outer surface of the test organisms, although no
      evidence was observed to show penetration of CNTs through cell membranes. The
      present study demonstrated that both the metals solubilized from CNTs such as
      nickel and the "metal-free" CNTs contributed to the toxicity.

PMID- 22610787
TI  - Clinical significance of monitoring serum adiponectin levels during intravenous
      pulse cyclophosphamide therapy in interstitial lung disease associated with
      systemic sclerosis.
AB  - OBJECTIVE: To investigate the clinical significance of monitoring serum
      adiponectin levels during intravenous pulse cyclophosphamide (IVCY) in systemic
      sclerosis (SSc) patients with interstitial lung disease (ILD). METHODS: Serum
      adiponectin levels were determined by a specific enzyme-linked immunosorbent
      assay in eight SSc patients with active ILD who underwent IVCY and 27 healthy
      controls. In patients, serum samples were drawn the day before each IVCY.
      RESULTS: Serum adiponectin levels were significantly decreased in SSc patients
      with active ILD before the first IVCY compared with healthy controls [median (25
      75 percentile): 3.21 (2.70-4.19) vs. 7.42 (6.06-10.82) MUg/ml; P < 0.01). After
      the completion of whole IVCY, serum adiponectin levels were significantly
      increased [17.55 (6.47-39.45) MUg/ml; P < 0.05] compared with the initial levels,
      and this increase significantly correlated with the decrease in ILD scores.
      Importantly, the dynamics of serum adiponectin levels during the IVCY therapy
      reflected its efficacy against SSc-ILD over the treatment and the follow-up
      period. CONCLUSION: The monitoring of serum adiponectin levels during the IVCY
      treatment may be useful to identify SSc patients with ILD refractory to the
      treatment and at high risk for exacerbations during the follow-up period.

PMID- 22610788
TI  - Sequential chemoradiotherapy with gemcitabine and cisplatin for locoregionally
      advanced nasopharyngeal carcinoma.
AB  - We investigated a new chemoradiotherapy (CRT) regimen for locoregionally advanced
      nasopharyngeal carcinoma (NPC). A total of 240 patients were randomly assigned to
      three different CRT regimens: sequential CRT [1 cycle chemotherapy + Phase I
      radiotherapy (RT) + 1 cycle chemotherapy + Phase II RT + 2 cycles chemotherapy]
      with a cisplatin-gemcitabine (GC) regimen (800 mg/m(2)  gemcitabine on Days 1 and
      8 and 20 mg/m(2)  cisplatin on Days 1-5, every 4 weeks) (sGC-RT); sequential
      chemoradiotherapy with a cisplatin-fluorouracil (PF) regimen (20 mg/m(2)  DDP and
      500 mg/m(2)  5-FU on Days 1-5, every 4 weeks) (sPF-RT) and cisplatin-based
      concurrent chemoradiotherapy plus adjuvant PF chemotherapy (Con-RT + PF). The
      complete response rate was higher in the sGC + RT group than in the other two
      groups (98.75% vs. 92.50%, p < 0.01). The 3-year overall survival (OS), disease
      free survival (DFS) and distant metastasis-free survival (DMFS) rates in the sGC
      RT group were significantly higher than those observed in the Con-RT group (OS,
      95.0% vs. 76.3%, p < 0.001; DFS, 89.9% vs. 67.5%, p < 0.001; DMFS, 92.5% vs.
      76.0%, p = 0.004) and in the sPF + RT group (OS, 95.0% vs. 73.6%, p < 0.001; DFS,
      89.9% vs. 63.3%, p < 0.001; DMFS, 92.5% vs. 74.7%, p = 0.002). There were no
      significant differences in 3-year OS, DFS and MFS rates between the Con-RT and
      the sPF-RT groups. The GC-RT group experienced more hematologic toxicity,
      constipation and rash; however, there were no differences in late RT toxicity
      between the groups. These results demonstrate that a sGC-RT regimen is effective
      and well tolerated in patients with locoregionally advanced NPC.

PMID- 22610789
TI  - Power-injectable ports: safety during placement, therapeutic use, and contrast
      administration during computed tomography procedures.
AB  - PURPOSE: To determine the safety of power-injectable ports during placement,
      therapeutic use, and administration of intravenous contrast material using
      automated mechanical injectors. METHODS: This retrospective, single institution
      study examined all patients undergoing placement of a power-injectable port
      between May 1, 2006 and June 30, 2010, with follow-up data collected through
      October 31, 2010. Electronic records and PACS were searched for patient
      demographics, placement indication, device placed, placement site, attending
      operator, and complications. The number of CECT scans performed for patients with
      indwelling ports, rate of port access for such studies, and contrast
      extravasation or device failure events during power injection of contrast were
      recorded and compared to the results of all other methods of venous access for
      CECT scans. RESULTS: In total, 313 ports were placed in 307 patients. Device
      dwell time ranged from 3 to 1506 days with a mean of 577. A total of 20 (6.5%)
      complications were identified during the study period, all of which were late.
      There was no statistically significant difference in complication rates between
      five attending operators. Patients with ports underwent 676 CECT scans during
      which the port was injected 142 times (20.9%). Neither extravasation nor device
      failure occurred during any scan, yielding no statistically significant
      difference when compared to the results of other venous access methods.
      CONCLUSIONS: Power-injectable tunneled catheters with attached subcutaneous ports
      are safe with low rates of complication during placement and dwell time. Power
      injection of contrast through these ports may be as safe as power injection using
      other venous access methods.

PMID- 22610790
TI  - Successful removal of a malpositioned hemodialysis catheter into the aortic arch.

PMID- 22610791
TI  - In vivo measurements of the contributions of protein synthesis and protein
      degradation in regulating cardiac pressure overload hypertrophy in the mouse.
AB  - Cardiac hypertrophy is generated in response to hemodynamic overload by altering
      steady-state protein metabolism such that the rate of protein synthesis exceeds
      the rate of protein degradation. To determine the relative contributions of
      protein synthesis and degradation in regulating cardiac hypertrophy in mice, a
      continuous infusion strategy was developed to measure myocardial protein
      synthesis rates in vivo. Osmotic mini-pumps were implanted in the abdominal
      cavity to infuse radiolabeled leucine in mice that are conscious and ambulatory.
      Protein synthesis rates were calculated by measuring incorporation of leucine
      into myocardial protein over 24 h prior to each time point and dividing by the
      specific radioactivity of plasma leucine. Compared to sham-operated controls,
      fractional rates of protein synthesis (K(s)) increased significantly at days 1
      and 3 of TAC, but was lower on day 7 and returned to control values by day 14.
      These changes coincided with the curvilinear increase in LV mass that
      characterizes the hypertrophic response. Fractional rates of protein degradation
      (K(d)) were calculated by subtracting the rate of myocardial growth from the
      corresponding K(s) value. K(d) fell at days 1 and 3 of TAC, increased at day 7
      and returned to control on day 14. Thus, the increase in LV mass generated in
      response to pressure overload is caused by acceleration of K(s) and suppression
      of K(d). As the growth rate slows, a new steady-state is achieved once the
      hypertrophic response is completed.

PMID- 22610793
TI  - S-Allylcysteine, a garlic compound, increases ABCA1 expression in human THP-1
      macrophages.
AB  - ATP-binding cassette transporter A1 (ABCA1) is a key mediator of cholesterol
      efflux to apoA-I in lipid-loaded macrophages, which is the first step of reverse
      cholesterol transport in vivo and a critical step in preventing atherosclerosis.
      Enhanced ABCA1 expression may inhibit foam cell formation and consequently reduce
      atherogenic risk. The purpose of this study was to investigate the effect of S
      allylcysteine (SAC), the most abundant organosulfur compound in aged garlic
      extract, on the expression of ATP-binding cassette transporter A1 in human THP-1
      macrophages. The human monocyte THP-1 cells were differentiated to macrophage
      cells in the presence of phorbol 12-myristate13-acetate (PMA). Macrophage cells
      were then treated with different concentrations (10, 20 and 40 mM) of SAC for 24
      h. Total RNA of treated macrophages was extracted and analyzed with real-time RT
      PCR. ABCA1 protein expression was also analyzed with western blotting. Results
      showed that SAC increased the ABCA1 mRNA (1.82-, 2.07- and 2.23-fold) and protein
      (1.37-, 1.55- and 2.08-fold) expression in macrophage THP-1 cells compared with
      control (untreated cells). Results suggested that SAC can increase ABCA1
      expression in macrophages and may be beneficial in promoting reverse cholesterol
      efflux.

PMID- 22610794
TI  - Identification of novel rare mutations of DACT1 in human neural tube defects.
AB  - Neural tube defects (NTDs) constitute the second most frequent cause of human
      congenital abnormalities. Complex multigenetic causes have been suggested to
      contribute to NTDs. The planar cell polarity (PCP) pathway plays a critical role
      in neural tube closure in model organisms and in human. Knockout of Dact1
      (Dapper, Frodo) leads to deregulated PCP signaling with defective neural tube in
      mice. Here, we report that five missense heterozygote mutations of the DACT1 gene
      are specifically identified in 167 stillborn or miscarried Han Chinese fetuses
      with neural tube defects. Our biochemical analyses revealed that among the five
      mutations, N356K and R45W show loss-of-function or reduced activities in inducing
      Dishevelled2 (DVL2) degradation and inhibiting jun-N-terminal kinase (JNK)
      phosphorylation, implicating mutated DACT1 as a risk factor for human NTDs. Our
      findings, together with early reports, suggest that rare mutations of the PCP
      related genes may constitute a great contribution to human NTDs.

PMID- 22610795
TI  - Severe hemolytic anemia associated with transient ischemic attack in a patient
      with HbH disease.

PMID- 22610792
TI  - Guanylyl cyclase/natriuretic peptide receptor-A signaling antagonizes the
      vascular endothelial growth factor-stimulated MAPKs and downstream effectors AP-1
      and CREB in mouse mesangial cells.
AB  - Along with its natriuretic, diuretic, and vasodilatory properties, atrial
      natriuretic peptide (ANP), and its guanylyl cyclase/natriuretic peptide receptor
      A (GC-A/NPRA) exhibit an inhibitory effect on cell growth and proliferation.
      However, the signaling pathways mediating this inhibition are not well
      understood. The objective of this study was to determine the effect of ANP-NPRA
      system on mitogen-activated protein kinases (MAPKs) and the downstream
      proliferative transcription factors involving activating protein-1 (AP-1) and
      cAMP-response element binding protein (CREB) in agonist-stimulated mouse
      mesangial cells (MMCs). We found that ANP inhibited vascular endothelial growth
      factor (VEGF)-stimulated phosphorylation of MAPKs (Erk1, Erk2, JNK, and p38), to
      a greater extent in NPRA-transfected cells (50-60 %) relative to vector
      transfected cells (25-30 %). The analyses of the phosphorylated transcription
      factors revealed that ANP inhibited VEGF-stimulated activation of CREB, and the
      AP-1 subunits (c-jun and c-fos). Gel shift assays demonstrated that ANP inhibited
      VEGF-stimulated AP-1 and CREB DNA-binding ability by 67 and 62 %, respectively.
      The addition of the protein kinase G (PKG) inhibitor, KT-5823, restored the VEGF
      stimulated activation of MAPKs, AP-1, and CREB, demonstrating the integral role
      of cGMP/PKG signaling in NPRA-mediated effects. Our results delineate the
      underlying mechanisms through which ANP-NPRA system exerts an inhibitory effect
      on MAPKs and down-stream effector molecules, AP-1, and CREB, critical for cell
      growth and proliferation.

PMID- 22610796
TI  - Modeling non-inherited antibiotic resistance.
AB  - A mathematical model is presented for the increase and decrease of non-inherited
      antibiotic resistance levels in bacteria. The model is applied to experimental
      data on E. coli exposed to amoxicillin or tetracyclin in different
      concentrations. The parameters of the model are estimated using a Monte Carlo
      Markov Chain method. The model accurately describes build-up and decline of
      antibiotic resistance caused by physiological adaptations as long as no genetic
      changes have occurred. The main conclusion of the analysis is that short time
      periods are sufficient to re-obtain low MIC-values after long-lasting exposure to
      these antibiotics.

PMID- 22610798
TI  - Shifting the paradigm: Nepal as a potential leader in the field of medical
      education.

PMID- 22610797
TI  - Effect of model selection on prediction of periodic behavior in gene regulatory
      networks.
AB  - One of the current challenges for cell biology is understanding of the system
      level cellular behavior from the knowledge of a network of the individual
      subcellular agents. We address a question of how the model selection affects the
      predicted dynamic behavior of a gene network. In particular, for a fixed network
      structure, we compare protein-only models with models in which each
      transcriptional activation is represented both by mRNA and protein
      concentrations. We compare linear behavior near equilibria for both cyclic
      feedback systems and a general system. We show that, in general, explicit
      inclusion of the mRNA in the model weakens the stability of equilibria. We also
      study numerically dynamics of a particular gene network and show significant
      differences in global dynamics between the two types of models.

PMID- 22610799
TI  - Standard setting in health professions education.

PMID- 22610800
TI  - Evolving experience in the management of empyema thoracis.
AB  - BACKGROUND: Empyema thoracis a disease of significant morbidity and mortality,
      especially in the developing world. However, the optimal management of empyema
      thoracis remains controversial. OBJECTIVE: To analyse evolving experience in
      clinical presentation, management, outcome and factors contributing to adverse
      morbidity in empyema thoracis. METHODS: This is hospital based retrospective
      study of patients who were diagnosed with empyema thoracis in cardiothoracic and
      vascular surgery (CTVS) unit, Bir Hospital, Kathmandu, Nepal over a period of one
      year (July 2009 to June 2010). A total of forty-six adult cases were categorized
      into two treatment groups: (i) thoracotomy for decortication (ii) segmentectomy,
      lobectomy and redo-thoracotomy for pneumonectomy. The median duration of illness
      prior to hospital admission was compared. The presence of loculated pleural fluid
      determined the need for thoracotomy. RESULTS: Out of forty-six cases, twenty-
      nine (63.04%) who had early thoracotomy (less than 22 days) had prompt
      symptomatic recovery. Fourteen out of seventeen (82.35%) of the patients who were
      initially treated with thoracocentesis or tube thoracostomy eventually needed
      thoracotomy. There was a positive shift in management towards early thoracotomy
      resulting in prompt symptomatic recovery. Significant complications were noted in
      eight patients who had delayed thoracotomy. Complications included recurrent
      empyema with lung abscess (n = 3), restrictive lung disease (n = 3),
      bronchopleural fistula (n = 1) and scoliosis (n=1). CONCLUSION: Early thoracotomy
      and decortication was found to be an excellent surgical procedure with good
      functional results and high patient satisfaction rate.

PMID- 22610801
TI  - Rectal misoprostol versus intramuscular oxytocin for prevention of post partum
      hemorrhage.
AB  - BACKGROUND: Postpartum hemorrhage (PPH) is an important cause of maternal
      morbidity and mortality especially in the developing countries.,Compared to
      expectant management, active management decreases the incidence of PPH.
      OBJECTIVE: To compare the effectiveness of rectal misoprostol with intramuscular
      oxytocin in the prevention of postpartum hemorrhage. METHODS: This is a
      prospective, randomized and analytical study from 1 st September 2009 to 28th
      February 2010 at Department of Obstetrics and Gynecology, Dhulkhel Hospital -
      Kathmandu University Hospital, Dhulikhel, Nepal. A total of 200 women were
      included to receive either 1000 micrograms rectal misoprostol tablets or 10 units
      of oxytocin intramuscularly. Primary outcome measures were the incidence of
      postpartum hemorrhage or a change in hematocrit or hemoglobin from admission to
      day two post delivery. Secondary outcome measures including severe postpartum
      hemorrhage and the duration of the third stage of labor were noted. Also the side
      effects of both misoprostol and oxytocin were recorded. RESULTS: The frequency of
      postpartum hemorrhage was 4% in the misoprostol subjects and 6% in the control
      subjects (P=0.886) There were no significant difference among the groups in the
      drop of hematocrit (P>0.05). Secondary outcome measures including severe
      postpartum hemorrhage and the duration of the third stage of labor were similar
      in both groups. Similarly, the side effects between the misoprostol and oxytocin
      group within 6 hours was statistically significant (p=0.003) whereas the side
      effects within 24 hours was statistically not significant (p=0.106). CONCLUSION:
      Rectal misoprostol is as effective as intravenous oxytocin in preventing
      postpartum hemorrhage with the similar incidence of side effects and is
      worthwhile to be used as a uterotonic agent for the routine management of third
      stage of labor.

PMID- 22610802
TI  - The prevalence of and risk factors for hypertension in adults living in central
      development region of Nepal.
AB  - BACKGROUND: Hypertension is the commonest cardiovascular disorder and now
      regarded as major public health problem. It is a precursor to major diseases like
      myocardial infarction, stroke, renal failure etc. There are very limited
      community based data on hypertension in Nepal, so, information on the prevalence
      of hypertension in the population is desirable. OBJECTIVES: To estimate the
      prevalence of hypertension and to explore the risk factors associated with
      hypertension. METHODS: In a cross sectional study , a total of 527 subjects
      (males n=214 and females n=313) participated in our study (age =18 years). The
      participants underwent anthropometric measurement and blood pressure and answered
      a pretested questionnaire. Hypertension was defined as per JNC VII criteria.
      RESULTS: Overall prevalence of hypertension was 22.4% (males: 32.7% and female:
      15.3%). Age specific prevalence of hypertension showed significant progressive
      increase in blood pressure ranging from 8% to 35%. Almost 40% of hypertensives
      did not know about their status. Bivariate analysis showed significant
      relationship of hypertension with gender, age, literacy, physical inactivity,
      body mass index (BMI), smoking and alcohol consumption. Multivariate analysis
      excluded literacy but all other risk factors continued to show positive
      association with hypertension. CONCLUSION: Being elderly, less physical activity,
      obese/overweight, smoking and alcohol consumption are significant risk factors of
      hypertension. Therefore, intervention measures are warranted emphasizing on
      modifiable risk factors such as smoking, alcohol consumption, physical activity
      and obesity to prevent hypertension.

PMID- 22610803
TI  - katG (SER 315 THR) gene mutation in isoniazid resistant Mycobacterium
      tuberculosis.
AB  - BACKGROUND Isoniazid (INH) together with Rifampicin (RFP) forms the cornerstone
      of a short chemotherapy course for tuberculosis (TB) treatment. Mutation at codon
      315 of katG gene is most prevalent in isoniazid resistant Mycobacterium
      tuberculosis (MTB) and is high in area with high TB incidence. Polymerase Chain
      Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) has been found to be
      a reliable and effective tool for the identification of the specific gene
      alteration. OBJECTIVE: The objective of this study was to screen Ser315Thr
      mutation of KatG gene of INH resistant MTB strain by PCR-RFLP technique. METHODS:
      Altogether 37 INHr MTB isolates obtained from German Nepal Tuberculosis Project
      (GENETUP) Kathmandu Nepal was included in the study. Deoxyribonucleic Acid (DNA)
      extraction was performed according to protocol of SORPOCLEAN from the culture
      isolates. Amplification of the fragment with katG codon 315 was performed in a
      Biometra Thermocycler using primers. The amplified fragment was cleaved with
      MspI. The restriction fragments obtained were electrophoresed in a 2% agarose gel
      and were visualized using transilluminator. RESULTS: The katG Ser315Thr mutation
      was observed in 23 (62.2%) out of 37 INH resistant isolates. The drug
      susceptibility profile of INHr MTB isolates showed all isolates to be resistant
      to INH and RFP whereas 26 and 27 MTB isolates were resistant to Ethambutol (EMB)
      and Streptomycin (S) respectively. Seventeen (17) patients were harbouring katG
      gene mutated strain among Ethambutol and Streptomycin resistant cases.
      CONCLUSION: The study identified high prevalence of Ser315Thr mutation in katG.
      The isolates harbouring this mutation were also simultaneously resistant to RFP.
      Ser315Th could be a potential genetic marker for predicting MDR-TB.

PMID- 22610804
TI  - Tissue polypeptide specific antigen as a marker used to determine the liver
      diseases.
AB  - BACKGROUND: Tissue polypeptide specific antigen and its specific M3 epitope are
      increased in malignant as well as in some benign diseases. The level of tissue
      polypeptide specific antigen in serum is related mostly to proliferation capacity
      rather than tumor mass and cell necrosis. OBJECTIVE: The aim of this study was to
      evaluate the levels of tissue polypeptide specific antigen and other tumor
      markers in patients with liver cirrhosis, chronic active hepatitis and hepatoma
      to determine if tissue polypeptide specific antigen is important to other tumor
      markers in hepatoma patients. METHODS: Ninety-seven patients and 30 controls were
      included in the study. The patients were divided into three subgroups as
      cirrhosis, hepatoma and chronic active hepatitis. The levels of tissue
      polypeptide specific antigen, carcinoembryonic antigen, CA19.9, alpha-fetoprotein
      and transaminases were determined in all patients. RESULTS: Tissue polypeptide
      specific antigen levels were significantly higher in all patients than in the
      control group (p less than 0.005) According to Kruskal-Wallis test with regard to
      subgroups, the differences in mean values of tissue polypeptide specific antigen
      and alpha-fetoprotein were significant (p less than 0.0001 for both). There was a
      low correlation between tissue polypeptide specific antigen and alpha-fetoprotein
      in the cirrhotic and hepatoma groups, but these were significantly correlated in
      the chronic active hepatitis group. The correlation coefficient between tissue
      polypeptide specific antigen and transaminases in all patients was low.
      CONCLUSIONS: Tissue polypeptide specific antigen is efficient for determining
      primary hepatoma patients and also that this marker is specific for proliferation
      of cells.

PMID- 22610805
TI  - Incidence and risk factor for ventilator-associated pneumonia in Kathmandu
      University Hospital.
AB  - BACKGROUND: Ventilator associated pneumonia is a major cause of morbidity in the
      intensive care unit. Difficulties in identification of the risk factors, in
      diagnosing and in prevention, have intensified the problem. OBJECTIVES: To
      measure the incidence of ventilator associated pneumonia in intensive care unit
      and to identify the risk factors associated. METHODS: A prospective observational
      cohort study was done in which we evaluated 69 patients who were mechanically
      ventilated for more than 48 hours to find out the development of nosocomial
      pneumonia and presence or absence of risk factors. Data were subjected to
      univariate analysis using chi-square and t-test. Level of significance was set at
      0.05. RESULTS: Twenty two (31.88%) out of 69 patients developed ventilator
      associated pneumonia, majority of them between four days to 14 days.
      Reintubation, invasive lines, H2 blockers and low PaO2/FiO2 were identified as
      major risk factors in our study. Enteral feeding via nasogastric tube and use of
      steroids was not associated with development of ventilator associated pneumonia.
      The patients with ventilator associated pneumonia had significantly longer
      duration of mechanical ventilation (18.88+/-7.7 days vs 7.36+/-4.19 days) and
      stay (29+/-17.8 days vs 9.22+/-5.14 days). The morality was similar for both the
      groups with or without ventilator associated pneumonia. CONCLUSION: The incidence
      of ventilator pneumonia is high. Patients requiring prolonged ventilation, re
      intubation, more invasive lines and H2 blockers, are at high risk and need
      special attention towards prevention.

PMID- 22610806
TI  - Trends of rotavirus in Nepal.
AB  - BACKGROUND: Rotavirus gastroenteritis is the major cause of morbidity and
      mortality in infants and young children worldwide. Safe and effective rotavirus
      vaccine is needed to have significant impact on severe rotavirus gastroenteritis.
      Currently, two live oral rotavirus vaccines have been licensed in many countries.
      Knowledge on distribution of human rotavirus of G and P types are essential
      before rotavirus vaccines are introduced in the target populations. OBJECTIVE: To
      observe the trends of rotavirus strains in children below five years of age,
      during the years, 2003-2005 in Nepal. METHODS: Stool specimen collected from
      children with acute diarrhea who were referred to observation unit or
      hospitalized in Kanti Children Hospital between 2003 and 2005 were examined.
      Meteorological data was obtained from Ministry of Environment, Nepal to examine
      the possibility on the impact of weather on rotavirus infection. RESULTS: Of 1250
      stool specimens, 271(22%) were positive for rotavirus by Rotaclone ELISA. G1 was
      the most common serotype in the first year of study, and G2 in the following
      year. G12 serotype emerged and remained predominant in two consecutive years. In
      addition, G9 and G3 emerged in the second year of the study. Children less than
      three years of age were commonly affected. The records reveal that rotavirus
      infection is related to the climate, and is commonly seen in the dry season,
      peaking in January. CONCLUSIONS: Continued surveillance of different regions is
      needed to monitor the trend of rotavirus strains and to establish rotavirus
      disease burden, which will help policy makers to make a decision in introducing
      rotavirus vaccine in Nepal.

PMID- 22610807
TI  - Culture proven bacterial meningitis in children: agents, clinical profile and
      outcome.
AB  - BACKGROUND: Meningitis is a serious infection. Little is known about the
      bacterial agents and their antibacterial sensitivity in Nepalese children.
      OBJECTIVES: To study bacteriological agents, clinical profile and immediate
      outcome in patients admitted to children ward of Patan Hospital with meningitis.
      METHODS: Prospective observational study conducted in paediatric ward of Patan
      Hospital. All the children admitted to the ward, with the diagnosis of culture
      proven bacterial meningitis on discharge were eligible. RESULTS: Out of 7,751
      children, 296 (3.8%) had meningitis. This was a group ranging from neonates to
      adolescents aged 18 years. Only 13 (4.4%) of cerebrospinal fluid samples taken
      from them yielded positive culture reports. The organisms were pneumococcus (6),
      Haemophilus influenza b (3), beta-hemolytic Streptococcus (1), a-hemolytic
      Streptococcus (1), N. meningitides (1) and Pseudomonas (1). Whereas Haemophilus
      influenza b was isolated from young infants, pneumococci were found in the young
      as well as the old. Fever, vomiting, high leukocyte count with left shift were
      all commonly present. All but one had cerebrospinal fluid pleocytosis. Low sugar
      and high protein was found in most specimens. Neuroimaging was done in six
      children of which three were abnormal (all young infants and pneumococci cases).
      Ceftriaxone was given to all but one child. Everybody recovered but three had
      complications, profound hearing loss and cortical atrophy with subdural
      collection in pneumococcal and septic arthritis with persistence of fever in
      Haemophilus influenzae b meningitis. CONCLUSION: The present study corroborates
      most of the epidemiological and clinical features of acute bacterial meningitis
      and sheds light on the causative agents of bacterial meningitis in Nepalese
      children.

PMID- 22610808
TI  - Outcome of pregnancy complicated by threatened abortion.
AB  - BACKGROUND: Threatened abortion is the most common complication in the first half
      of pregnancy. Most of these pregnancies continue to term with or without
      treatment. Spontaneous abortion occurs in less than 30% of these women.
      Threatened abortion had been shown to be associated with increased incidence of
      antepartum haemorrhage, preterm labour and intra uterine growth retardation.
      OBJECTIVE: This study was to asses the outcome of threatened abortion following
      treatment. METHODS: This prospective study was carried out in Dhulikhel Hospital 
      Kathmandu University Hospital from January 2009 till May 2010. Total 70 cases of
      threatened abortion were selected, managed with complete bed rest till 48 hrs of
      cessation of bleeding, folic acid supplementation, uterine sedative, and hormonal
      treatment till 28 weeks of gestation. Ultrasonogram was performed for diagnosis
      and to detect the presence of subchorionic hematoma. Patients were followed up
      until spontaneous abortion or up to delivery of the fetus. The measures used for
      the analysis were maternal age, parity, gestational age at the time of
      presentation, previous abortions, presence of subchorionic hematoma, complete
      abortion, continuation of pregnancy, antepartum hemorrhage, intrauterine growth
      retardation and intrauterine death of fetus. RESULTS: Out of 70 cases
      subchorionic haematoma was found in 30 (42.9%) cases. There were 12 (17.1%)
      patients who spontaneously aborted after diagnosis of threatened abortion during
      hospital stay, 5 (7.1%) aborted on subsequent visits while 53 (75.8%) continued
      pregnancy till term. Among those who continued pregnancy intrauterine growth
      retardation was seen in 7 (13.2%), antepartum hemorrhage in 4 (7.5%), preterm
      premature rupture of membrane in 3 (5.66%) and IUD in 3 (5.66%). Spontaneous
      abortion was found more in cases with subchorionic hematoma of size more than 20
      cm2. CONCLUSION: In cases of threatened abortion with or without the presence of
      subchorionic hematoma, prognostic outcome is better following treatment with bed
      rest, uterine sedatives, folic acid supplementation and hormonal treatment.

PMID- 22610810
TI  - Outcome of adolescent pregnancy at Kathmandu University Hospital, Dhulikhel,
      Kavre.
AB  - BACKGROUND: Adolescence Pregnancy is a social problem worldwide with serious
      implication of maternal and child health. This study purposed to compare the
      maternal and neonatal outcome of the teenage mothers (15- 19 years) with that of
      the young mothers (20-24 years) to determine if adolescent pregnancies have
      increased risk of adverse outcomes. OBJECTIVES: This study aims to find out the
      outcomes of adolescent pregnancy at Kathmandu University Hospital, Dhulikhel
      Hospital, Kavre. METHODS: Descriptive cross sectional study was done. The study
      included all primiparous mothers of age 15-19 (n=168) and 20-24 (n=401) recorded
      in the delivery record book of Dhulikhel Hospital from June 2007 to May 2008. Chi
      square test and relative risk (RR) for subgroups of study population was examined
      using the SPSS version 10.0. RESULTS: The low birth weight baby among teenage
      mothers and young mothers were 28% and 26.7% respectively (p=0.572). The Relative
      risk of low birth weight among adolescent is 1.1 (0.75-1.684) times to that of
      young mothers at 95% confidence interval. Preterm birth was not associated with
      adolescence pregnancy (7% Vs. 11.5%, p=0.141). Normal delivery was the common
      mode of delivery among both groups (77.4% Vs. 74.6%). Among the neonatal
      complication, newborns of adolescents had greater neonatal complications than
      newborns of the young mothers (17.2% Vs 16.7%). Maternal complication like
      antepartum hemorrhage (2.4% Vs. 1.7%) and postpartum hemorrhage (0.6% Vs. 0.2%)
      was higher among adolescents. CONCLUSIONS: Low birth weight, common neonatal
      complication, antepartum hemorrhage and postpartum hemorrhage are found more in
      adolescent group, however statistically insignificant.

PMID- 22610809
TI  - Clinical profile of invasive pneumococcal diseases in Patan Hospital, Nepal.
AB  - BACKGROUND: Pneumococcal infection is one of the leading causes of pneumonia,
      meningitis and septicemia in developing countries. It accounts for one million
      deaths each year in children. OBJECTIVES: The objective of this study is to see
      the clinical profile of invasive pneumococcal disease, antibiotics sensitivity
      pattern and prevalent serotypes in children admitted at Patan Hospital. METHODS:
      This is a retrospective analytical study conducted in the department of
      Paediatrics, Patan hospital. The lab data of those children who grew pneumococci
      in their blood, cerebrospinal fluid or body fluids over a period of 3 years
      (January 2007 to Dec 2009) were collected and the case files were then studied.
      RESULTS: Out of 42 cases of invasive pneumococcal diseases studied admitted
      diagnoses included pneumonia, febrile seizure, bacteremia or septicemia,
      meningitis, acute gastroenteritis and glomerulonephritis. Twenty seven of them
      were children under five. The male to female ratio was 1.7:1. On investigation
      64%, 52% and 5% of the patients had leucocytosis, anaemia, and leucopenia
      respectively. Twenty six of them had radiological changes suggestive of
      pneumonia. Streptococcus pneumoniae grew in 38 blood samples, 5 cerebrospinal
      fluid and 3 pleural fluids. Almost all of these isolates were sensitive to
      penicillin, cefotaxime, amoxycillin, choloramphenicol, erythromycin and ofloxacin
      and resistant to cotrimoxazole and gentamicin. Pneumococcal serotypes found in
      our study were 1, 14, 5, 23B, 6B, 8, 9A, 9V, 10A, 15 and 23F (11 serotypes).
      CONCLUSIONS: Penicillin is still the most effective antibiotic for streptococcal
      infection in our study. Of the pneumococcal serotypes identified; 36% were
      covered by the 7-valent pneumococcal conjugate vaccine, 54% each by PCV-10 and
      PCV-13, and 72% by the e 23 valent vaccines.

PMID- 22610811
TI  - Ocular trauma in patients presenting to Dhulikhel Hospital.
AB  - BACKGROUND: Ocular trauma is an important cause of blindness and ocular morbidity
      throughout the world. Prevalence studies help to define the target group, plan
      strategies and thereby lessen trauma related blindness in the country. OBJECTIVE:
      To identify the risk factors for ocular trauma, those at risk, describe the
      visual acuity at time of clinical presentation, and assess the nature and
      severity of ocular trauma in patients presenting to Dhulikhel Hospital emergency
      department and eye OPD with ocular trauma. METHODS: It is a descriptive and
      prospective study of all the patients with ocular trauma presenting to Dhulikhel
      Hospital from December 2009 to December 2010. A complete history and detailed
      ophthalmologic evaluation was done and noted down. RESULTS: There were 112
      subjects with ocular trauma. Mean age was 28.43+/-16.36 years with a range of one
      year to 74 years. Males predominated with 72.3% frequency (p less than 0.001).
      Incidence peaked in third decade of life (p less than 0.01). Ocular trauma peaked
      in months of September and October. Presenting visual acuity better than 6/12 was
      noted in 83.9% of cases whereas 2.7% of cases had visual acuity of less than
      3/60. Household (56.3%, p less than 0.001) was the commonest place of injury with
      wooden objects (19.6%) being the commonest object of injury. Most of the injuries
      were mechanical (85.7%, p>0.001). CONCLUSION: Blunt injuries were more common in
      young males. Household and workplace were common location of ocular injuries.
      Public awareness and strict legislation to use personal protective devices can
      help to reduce the occurrence of ocular injury.

PMID- 22610812
TI  - Comparison of sniffing position and simple head extension for visualization of
      glottis during direct laryngoscopy.
AB  - BACKGROUND: The ability of good glottis visualization during direct laryngoscopy
      is major determinant of easy tracheal intubation. Sniffing position for
      laryngoscopy is considered as gold standard and ideal position. Several studies
      have questioned the validation of sniffing potion. OBJECTIVES: This study aims to
      compare relative efficacy of sniffing position and simple head extension for
      visualization of glottis during direct laryngoscopy. METHODS: Four hundred
      patients undergoing elective surgery under general anesthesia requiring
      endotracheal intubation were randomized into two groups and study was concluded.
      Glottic visualization was assessed using modified Cormack and Lehane
      classification. After laryngoscopy, tracheal intubation was performed and
      intubation difficulty scale was noted. RESULTS: Both the groups were comparable
      regarding glottis visualization. Both the groups were comparable in demographic
      profiles. All the intubation difficulty scale variables were comparable in both
      the groups except N3. Total Intubation Difficulty Score was better in sniffing
      position than in simple head extension group. CONCLUSION: Glottic visualization
      and intubation difficulty score was better in sniffing position as compared to
      simple head extension.

PMID- 22610813
TI  - Tricuspid valve repair: DeVega's tricuspid annuloplasty in moderate secondary
      tricuspid regurgitation.
AB  - BACKGROUND: Moderate secondary tricuspid incompetence has variable natural
      history if left unattended during mitral valve surgery. Recent data suggest
      progression of the secondary tricuspid incompetence over time.Secondary moderate
      tricuspid regurgitation in rheumatic mitral valve disease may regress after
      mitral valve surgery without direct intervention. OBJECTIVES: The present study
      was done to assess early result of DeVega tricuspid valve annuloplasty amongst
      those with moderate tricuspid regurgitation due to rheumatic mitral valve
      disease. METHODS: Group I(mitral value replacement with tricuspid repair) and
      group II (mitral value replacement only).The two groups were followed up at three
      months post-operatively and evaluated for their functional class and
      echocardiography variables. RESULTS: There were 43 patients who underwent mitral
      valve replacement with moderate tricuspid regurgitation. 23 underwent mitral
      valve replacement with tricuspid repair group (Group 1). Most of the patients
      were women (28/43). The mean age was 31.4 + 14.8 and 25.13 + 9.4 years. Group I
      had 21(91.3%) and Group II had 17 (85%) in NYHA class III and IV. The pre
      operative echocardiographic cardiac left ventricular and left atrial dimensions,
      Left ventricular function and valve lesions were statistically similar for both
      groups, except PASP was higher amongst tricuspid repair (Group 1: 38.60 + 12.75
      mHg, Group 2: 61.52 + 19.76 mmHg; p equals or less than 0.05). At three month
      review after surgery, four patients were in NYHA II amongst those without
      tricuspid repair (Group II), whilst the rest were in NYHA I. Left ventricular
      dimensions, Left Ventricular function and valve prosthetic valve function were
      similar between groups. Eleven (47.8%) patients in Group I and only five (25%) of
      Group II had trace or less TR at the follow-up. This was found to be
      statistically significant on chi square test (p less than 0.05). There were 7
      (16.2%) patients who had persistent moderate TR. Higher PASP and larger LV
      dimensions at three months were predictive of persistent moderate TR. CONCLUSION:
      Mitral valve replacement does decrease the severity of tricuspid regurgitation
      amongst those with secondary moderate tricuspid regurgitation by at least one
      grade, but DeVega's annuloplasty confers a better repair result.

PMID- 22610814
TI  - Drowsy drivers--medical implication of highway traffic safety.
AB  - The estimates of the contribution of drowsiness and fatigue to the number of road
      crashes is often neglected considerably, due both to under-reporting of these
      factors by drivers, and technical difficulty in investigating the problem.
      Preventing and treating the reasons for falling asleep behind the wheel may have
      considerable contribution in traffic safety. Therefore the licensing authorities
      in co-operation with the medical profession should attend more closely to the
      issue of sleep related disorders and their implications for driving in cases with
      notoriously high risk. The police and other enforcement authorities need
      appropriate knowledge and procedures to detect drivers at risk of falling asleep
      while driving. Considering the increasing number of road traffic accidents day
      per day, it is a need of the hour to detect drivers possibly at risk, and to take
      appropriate precautions in terms of education, advice and treatment regimes, as
      well as restrictions on licensing.

PMID- 22610815
TI  - Multiple variations of branches of abdominal aorta.
AB  - The abdominal aorta and its major branches supply oxygenated blood to nearly all
      the organs in the abdominal cavity. During routine dissection (January 2009) of a
      middle aged male cadaver at Dr. PSIMS, Gannavaram, Krishna Dist. (INDIA), the
      following variations of branches of abdominal aorta were found. The coeliac trunk
      gave off three branches. The first branch was left inferior phrenic artery which
      arose directly from coeliac trunk. The second branch bifurcates into left gastric
      artery and accessory hepatic artery for left lobe of liver. The second branch
      gave off splenic artery and common hepatic artery. The right testicular artery
      took its origin from right aberrant renal artery. This variation was associated
      with the presence of bilateral aberrant renal arteries for lower poles of both
      kidneys arising from abdominal aorta and aberrant renal arteries bilateral for
      upper poles originating from the renal arteries. Anatomical variation of
      testicular arteries is reported to be 4.7 %. Apart from creating hazards during
      abdominal surgery, vascular variation can also become a technical problem for
      infusion therapy and chemoembolisation of neoplasm in the liver.

PMID- 22610816
TI  - Giant parathyroid adenoma.
AB  - Primary Hyperparathyroidism is most commonly caused by parathyroid adenoma.
      Parathyroid adenoma is generally suspected by certain symptoms and biochemical
      abnormalities. They rarely attain large size to be evident clinically. We report
      a rare case of giant parathyroid adenoma measuring 5 x 4 x 3 cm and weighing 35
      gm.

PMID- 22610817
TI  - Impalement injury to the heart.
AB  - Cardiac impalement injury is rare and one of the most severe penetrating chest
      injuries, often fatal. The management of penetrating cardiac injuries is a
      challenging one. The success in management of impaling cardiac trauma requires
      stabilization of the impaling object, expeditious transfer to a facility for open
      heart surgery, rapid imaging, access to blood and blood products and a ready
      surgical team. We report a case of impalement injury to the heart by a stick,
      transfixing the right ventricle and its successful treatment.

PMID- 22610818
TI  - Differential effects of vitamin D treatment on inflammatory and non-inflammatory
      breast cancer cell lines.
AB  - Vitamin D is a known regulator of breast cancer cell proliferation, apoptosis,
      migration, invasion and differentiation in vitro. Recent studies have suggested a
      preventative role for vitamin D in breast cancer development and suggested a
      possible therapeutic application of vitamin D for patients with various forms of
      breast cancer. Inflammatory breast cancer (IBC) is a highly aggressive and
      phenotypically unique form of breast cancer that has a very poor prognosis. IBC
      invades the dermal lymphatics of the breast as tumor emboli early in the course
      of the disease. Because of the invasive nature of IBC, novel therapeutics are
      needed desperately. In the current study we examined the effect of the active
      form of vitamin D, calcitriol, treatment on the aggressive IBC phenotype. Herein
      we demonstrate that although the vitamin D receptor (VDR) is present in both IBC
      and non-IBC cell lines, the effect of vitamin D treatment is significant only on
      the IBC cells. SUM149 IBC cells showed increased protein concentration in
      response to 24 h of calcitriol exposure; likely mediated by an increase in
      protein synthesis as opposed to increased cellular proliferation. In addition,
      treatment with 100 nM calcitriol showed a significant decrease in SUM149
      migration (67.8 % decrease, P = 0.030), invasion (43.9 % decrease, P = 0.015),
      and tumor spheroid size (69.4 % decrease, P = 0.018) compared to nontreated
      control groups. Finally, calcitriol treatment of SUM149 cells led to
      significantly fewer IBC experimental metastases as compared to control. Our study
      demonstrates that calcitriol treatment of SUM149 affected several of the
      processes important for IBC metastasis but had little effect on MDA-MB-231 cells.
      Therefore, calcitriol treatment may have the potential to decrease the rate and
      incidence of metastasis in IBC patients.

PMID- 22610820
TI  - Pathogenesis of cholestatic itch: old questions, new answers, and future
      opportunities.

PMID- 22610819
TI  - Rheology and DWS microrheology of concentrated suspensions of the semiflexible
      filamentous fd virus.
AB  - Microrheology measurements were performed on suspensions of bacteriophage fd with
      diffusive wave spectroscopy in the concentrated regime, at different values of
      ionic strength. Viscosity vs. shear rate was also measured, and the effect of
      bacteriophage concentration and salt addition on shear thinning was determined,
      as well as on the peaks in the viscosity vs. shear curves corresponding to a
      transition from tumbling to wagging flow. The influence of concentration and salt
      addition on the mean square displacement of microspheres embedded in the
      suspensions was determined, as well as on their viscoelastic moduli up to high
      angular frequencies. Our results were compared with another microrheology
      technique previously reported where the power spectral density of thermal
      fluctuations of embedded micron-sized particles was evaluated. Although both
      results in general agree, the diffusive wave spectroscopy results are much less
      noisy and can reach larger frequencies. A comparison was made between measured
      and calculated shear modulus. Calculations were made employing the theory for
      highly entangled isotropic solutions of semiflexible polymers using a tube model,
      where various ways of calculating the needed parameters were used. Although some
      features are captured by the model, it is far from the experimental results
      mainly at high frequencies.

PMID- 22610821
TI  - Benzo[a]pyrene modulation of acute immunologic responses in Red Sea bream
      pretreated with lipopolysaccharide.
AB  - The effects of polycyclic aromatic hydrocarbons (PAHs) have been reported to
      modulate the immune response in aquatic animals, but the collected information of
      their effects on fish immunity is so far ambiguous. This study demonstrated that
      Benzo[a]pyrene (BaP) exposure altered the expression pattern of an antimicrobial
      peptide hepcidin (PM-hepc) gene and the activities of some immune-associated
      parameters in the lipopolysaccharide (LPS)-challenged red sea bream (Pagrus
      major). It was observed that LPS could increase respiratory burst, lysozyme and
      antibacterial activity in P. major. However when the P. major was exposed to
      different concentrations of BaP (1, 4, or 8 MUg L(-1) ) for 14 days and then
      challenged with LPS there was no significant change in the lysozyme and
      antibacterial activity. It was further observed that LPS could induce the PM-hepc
      mRNA expression at 3, 6, and 12-h post-LPS challenge. However, when P. major was
      exposed first to BaP for 14 days and then challenged with LPS, the expression of
      PM-hepc mRNA was delayed in the liver until 24 h and not significantly induced
      until 48 and 96 h. The mRNA expression pattern was completely different from that
      only with LPS challenge, showing that BaP exposure changed the PM-hepc mRNA
      expression pattern of fish with LPS challenge. This study demonstrated that BaP
      exposure can weaken or inhibit the induction of lysozyme and antibacterial
      activity in the LPS-challenged P. major; conversely BaP exposure could enhance
      the mRNA expression of PM-hepc gene, indicating that the effect of BaP has
      different modulatory mechanism on hepcidin genes and immune-associated
      parameters.

PMID- 22610822
TI  - Highlights of the Keystone Symposium: sirtuins in metabolism, aging and disease.
AB  - From February 12-16, 2012, leading members of the sirtuin scientific community
      assembled in Tahoe, CA to attend the Keystone Symposium "Sirtuins in Aging,
      Metabolism, and Disease." It was a vibrant and lively meeting, and in the spirit
      of Keystone Symposia, both established sirtuin researchers and those new to the
      field enjoyed a unique opportunity to interact and exchange ideas.

PMID- 22610824
TI  - Metabolic-intermediate complex formation with cytochrome P450: theoretical
      studies in elucidating the reaction pathway for the generation of reactive
      nitroso intermediate.
AB  - Mechanism-based inhibition (MBI) of cytochrome P450 (CYP) can lead to drug-drug
      interactions and often to toxicity. Some aliphatic and aromatic amines can
      undergo biotransformation reactions to form reactive metabolites such as
      nitrosoalkanes, leading to MBI of CYPs. It has been proposed that the
      nitrosoalkanes coordinate with the heme iron, forming metabolic-intermediate
      complex (MIC), resulting in the quasi-irreversible inhibition of CYPs. Limited
      mechanistic details regarding the formation of reactive nitroso intermediate and
      its coordination with heme-iron have been reported. A quantum chemical analysis
      was performed to elucidate potential reaction pathways for the generation of
      nitroso intermediate and the formation of MIC. Elucidation of the energy profile
      along the reaction path, identification of three-dimensional structures of
      reactive intermediates and transition states, as well as charge and spin density
      analyses, were performed using the density functional B3LYP method. The study was
      performed using Cpd I [iron (IV-oxo] heme porphine with SH(-) as the axial
      ligand) to represent the catalytic domain of CYP, simulating the
      biotransformation process. Three pathways: (i) N-oxidation followed by proton
      shuttle, (ii) N-oxidation followed by 1,2-H shift, and (iii) H-abstraction
      followed by rebound mechanism, were studied. It was observed that the proton
      shuttle pathway was more favorable over the whole reaction leading to reactive
      nitroso intermediate. This study revealed that the MIC formation from a primary
      amine is a favorable exothermic process, involving eight different steps and
      preferably takes place on the doublet spin surface of Cpd I. The rate-determining
      step was identified to be the first N-oxidation of primary amine.

PMID- 22610823
TI  - A new technology for detecting cerebral blood flow: a comparative study of
      ultrasound tagged NIRS and 133Xe-SPECT.
AB  - There is a need for real-time non-invasive, continuous monitoring of cerebral
      blood flow (CBF) during surgery, in intensive care units and clinical research.
      We investigated a new non-invasive hybrid technology employing ultrasound tagged
      near infrared spectroscopy (UT-NIRS) that may estimate changes in CBF using a
      cerebral blood flow index (CFI). Changes over time for UT-NIRS CFI and 133Xenon
      single photon emission computer tomography (133Xe-SPECT) CBF data were assessed
      in 10 healthy volunteers after an intravenous bolus of acetazolamide. UT-NIRS CFI
      was measured continuously and SPECT CBF was measured at baseline, 15 and 60 min
      after acetazolamide. We found significant changes over time in CFI by UT-NIRS and
      CBF by SPECT after acetazolamide (P <= 0.001). Post hoc tests showed a
      significant increase in CFI (P = 0.011) and SPECT CBF (P < 0.001) at 15 min after
      acetazolamide injection. There was a significant correlation between CFI and
      SPECT CBF values (r = 0.67 and P <= 0.033) at 15 min, but not at 60 min (P >=
      0.777). UT-NIRS detected an increase in CFI following an acetazolamide bolus,
      which correlated with CBF measured with 133Xe-SPECT. This study demonstrates that
      UT-NIRS technology may be a promising new technique for non-invasive and real
      time bedside CBF monitoring.

PMID- 22610827
TI  - Intimate partner violence and belief systems in Liberia.
AB  - Intimate partner violence is endemic in parts of the African continent. A small
      scale survey (n = 229) was conducted in 2009 in Northern Liberia, West Africa, to
      determine the prevalence and nature of intimate partner violence, and the
      cultural beliefs and gender norms that underpin respondent experiences and views
      towards intimate partner violence. Results show widespread experience of intimate
      partner violence among the respondent group, including physical abuse, sexual and
      verbal, and economic abuse. Acceptance of the situation was identified by most
      respondents as a way of responding to violence, and arises from the lack of
      financial and legal supports for women within the community. Despite the range of
      abuses experienced, beliefs about the power position of men in Liberian society
      provide evidence to reflect the predominance of certain cultural beliefs in
      framing respondents' perceptions of gender relations. The article concludes with
      a discussion on the possible impact of Liberia's recent conflict in contributing
      to the perpetuation and normalization of intimate partner violence. Further large
      scale research in this area is required.

PMID- 22610826
TI  - Body mass index and survival in patients with renal cell carcinoma: a clinical
      based cohort and meta-analysis.
AB  - Growing evidence suggests that obesity, an established cause of renal cell cancer
      (RCC), may also be associated with a better prognosis. To evaluate the
      association between RCC survival and obesity, we analyzed a large cohort of
      patients with RCC and undertook a meta-analysis of the published evidence. We
      collected clinical and pathologic data from 1,543 patients who underwent
      nephrectomy for RCC between 1994 and 2008 with complete follow-up through 2008.
      Patients were grouped according to BMI (kg/m(2) ): underweight <18.5, normal
      weight 18.5 to <23, overweight 23 to <25 and obese >=25. We estimated survival
      using the Kaplan-Meier method and Cox proportional hazard models to examine the
      impact of BMI on overall survival (OS) and cancer-specific survival (CSS) with
      adjustment for covariates. We performed a meta-analysis of BMI and OS, CSS and
      recurrence-free survival (RFS) from all relevant studies using a random-effects
      model. The 5-year CSS increased from 76.1% in the lowest to 92.7% in the highest
      BMI category. A multivariate analysis showed higher OS [hazard ratio (HR) = 0.45;
      95% CI: 0.29-0.68) and CSS (HR = 0.47; 95% CI: 0.29-0.77] in obese patients than
      in normal weight patients. The meta-analysis further corroborated that high BMI
      significantly improved OS (HR = 0.57; 95% CI: 0.43-0.76), CSS (HR = 0.59; 95% CI:
      0.48-0.74) and RFS (HR = 0.49; 95% CI: 0.30-0.81). Our study shows that
      preoperative BMI is an independent prognostic indicator for survival among
      patients with RCC.

PMID- 22610825
TI  - Different effects of omega-3 fatty acids on the cell cycle in C2C12 myoblast
      proliferation.
AB  - Polyunsaturated fatty acids (PUFAs) are important molecules for human health. We
      investigated the effects of three major omega-3 PUFAs on C2C12 myoblast
      proliferation. Both docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids
      decreased cell growth, whereas linolenic (ALA) acid did not, compared with the
      control. Cell cycle analysis showed that G(1) phase duration was increased
      markedly and S-phase duration was decreased by DHA and EPA. In contrast, there
      was no change in the G(1) or S-phase duration when the cells were treated with
      linolenic acid. To determine how DHA and EPA affected the cell cycle, cyclins and
      MAPK proteins were investigated. Western blotting and real-time quantitative PCR
      showed that DHA and EPA decreased cyclin E and CDK2 levels at both the protein
      and mRNA level. Also, MAPK phosphorylation levels were decreased by treatment
      with DHA and EPA. Our results indicated that different kinds of n-3 PUFA
      differentially affected myoblast cell proliferation. DHA and EPA decreased
      skeletal muscle cell proliferation through a mechanism involving MAPK-ERK.

PMID- 22610828
TI  - Social bonds and the role of school-based victimization.
AB  - This study explores the impact of school-based victimization on the adolescent's
      social bond. Previous research has provided empirical support for Hirschi's
      social control theory that the strength of the adolescent's social bond is
      associated with the probability that he or she will engage in criminal offending.
      However, research identifying what factors influence the strength of the
      adolescent's social bond is limited. In addition, research has established that
      school-based victimization is associated with numerous negative outcomes,
      including diminished educational outcomes and criminal offending. Therefore, it
      is plausible that school-based victimization undermines the adolescent's social
      bonds to school. Using a sample of 10th-grade students from the Educational
      Longitudinal Study of 2002, HLM models were developed to explore the relationship
      between school-based victimization and the adolescent's social bond to school.
      The results suggest that school-based victimization has a negative association
      with three elements of the adolescent's social bond to school: attachment,
      commitment, and belief. This study demonstrates the need for further research to
      identify the determinants of the strength of the adolescent's social bond to
      school.

PMID- 22610829
TI  - Suicide risk among violent and sexual criminal offenders.
AB  - Risk of suicide in people who have perpetrated specific forms of violent or
      sexual criminal offenses has not been quantified accurately or precisely. Also,
      gender comparisons have not been possible due to sparse data problems in the
      smaller studies that have been conducted to date. We therefore aimed to estimate
      these effects in the whole Danish population over a 26-year period. By completely
      interlinking national criminal, psychiatric, sociodemographic and cause-specific
      mortality registers, we conducted a nested case-control study of more than 27,000
      adult suicides, during 1981-2006, and more than half a million age and gender
      matched living controls. Elevated suicide risk was found in male sexual
      offenders. Risk was even higher among violent offenders, with greater effect
      sizes seen in females. It was markedly raised with serious violence, reaching a
      peak in relation to homicide or attempted homicide: male odds ratio (OR) 12.0,
      95% confidence interval (CI) [8.3, 17.3]; female OR 30.9, CI [11.9, 80.6].
      Following adjustment for psychiatric and social risk factors, relative risk in
      violent offenders was comparable to that seen among nonviolent offenders. These
      findings underline the importance of understanding why some people are violent
      toward themselves as well as other people, and why suicide risk is so much higher
      in people who have perpetrated serious acts of violence. They also indicate a
      clear need for developing effective multiagency interventions that effectively
      tackle both forms of destructive behavior.

PMID- 22610830
TI  - Personality correlates of aggression: evidence from measures of the five-factor
      model, UPPS model of impulsivity, and BIS/BAS.
AB  - Although many studies of personality and aggression focus on multidimensional
      traits and higher order personality disorders (e.g., psychopathy), lower order,
      unidimensional traits may provide more precision in identifying specific aspects
      of personality that relate to aggression. The current study includes a
      comprehensive measurement of lower order personality traits in relation to three
      forms of aggression: reactive, proactive, and relational. Traits related to
      interpersonal antagonism and impulsivity, especially impulsive behavior in the
      context of negative affect, were consistently related to aggression across
      multiple indices. These findings suggest that certain lower order traits are of
      critical importance to understanding who engages in aggressive behavior and why
      this behavior occurs.

PMID- 22610831
TI  - Men as victims: "victim" identities, gay identities, and masculinities.
AB  - The impact and meanings of homophobic violence on gay men's identities are
      explored with a particular focus on their identities as men and as gay men.
      Homosexuality can pose a challenge to conventional masculinities, and for some
      gay men, being victimized on account of sexual orientation reawakens conflicts
      about their masculinity that they thought they had resolved. Being victimized can
      reinvoke shame that is rooted in failure or unwillingness to uphold masculine
      norms. For some gay men, victimization therefore has connotations of
      nonmasculinity that make being a victim an undesirable status, yet that status
      must be claimed to obtain a response from criminal justice or victim services.
      Men who experience homophobic abuse are helped by accepting a victim identity,
      but only if they can quickly move on from it by reconstructing a masculine gay
      (nonvictim) identity. This process can be facilitated by agencies such as the
      police and victim services, provided they help men exercise agency in "fighting
      back," that is, resisting further victimization and recovering.

PMID- 22610832
TI  - Sexual victimization among Spanish college women and risk factors for sexual
      revictimization.
AB  - Sexual revictimization is frequent among victims of child sexual abuse. Several
      variables, such as sexual experience, substance abuse, and sexual assertiveness,
      have been proposed to explain the link between child sexual abuse and adolescent
      and adult sexual victimization, although they have typically been tested
      separately. The main objective of this study was to analyze which of these
      variables better explains the revictimization phenomenon using a multiple
      mediation analysis. The study also tested the frequency of sexual victimization
      experiences in a Spanish sample of college women. Four hundred and two women were
      interviewed. Results showed that 30.4% of them engaged in undesired sexual
      contact while almost 4% were victims of rape. The most frequent perpetrators were
      partners or ex-partners, acquaintances, or dating partners, but not strangers.
      Finally, the relationship between child sexual abuse and adolescent and adult
      sexual victimization was mediated by number of consensual sexual partners and
      sexual assertiveness. Results reflect some cultural differences from previous
      research.

PMID- 22610833
TI  - Social norms for intimate partner violence in situations involving victim
      infidelity.
AB  - The present study investigated perceived descriptive norms (i.e., perceived
      prevalence) for male-to-female intimate partner violence (IPV) following victim
      infidelity (i.e., girlfriend had sex with another man). While watching a video
      taped vignette of a young, dating couple in an argument that escalated to male-to
      female violence, male participants were asked various questions to assess
      perceived descriptive norms at several time points during the escalating
      argument. Half of the participants were told that the victim in the video was
      unfaithful. Results suggested that while participants did believe that it was
      much more common for their male friends and for typical male students to aggress
      against unfaithful girlfriends compared to faithful girlfriends, these
      differences were less pronounced as the aggression intensified. When testing
      whether perceived norms for IPV were related to participants' purported risk of
      engaging in IPV, a clear pattern appeared: For the no-infidelity condition, IPV
      perceived norms for male friends and perceived norms for typical male students
      were each significantly related to participants' likelihood of engaging in IPV,
      such that the higher the estimated norm, the higher the participants' risk.
      However, for the infidelity condition, only perceived norms for male friends were
      related to the risk of engaging in IPV. Findings have important implications for
      social norms-based intervention and prevention programs for IPV on college
      campuses.

PMID- 22610834
TI  - Relationships between maternal emotion regulation, parenting, and children's
      executive functioning in families exposed to intimate partner violence.
AB  - Recently researchers have begun to explore the extent to which children's
      cognitive development is influenced by experiences in the family environment.
      Assessing mother-child dyads exposed to intimate partner violence (IPV), a
      population at risk for emotional and neurocognitive problems, we examined
      relationships between maternal emotional regulation, parenting, and children's
      executive functioning (including working memory, inhibitory control, cognitve
      flexibility and set shifting, and planning). Positive parenting practices, as
      reported by the children, were correlated with children's planning and problem
      solving performance. Controlling for children's own emotion regulation and
      gender, mothers' self-reported emotion regulation abilities predicted children's
      performance on a task of cognitive flexibility. Girls exhibited superior emotion
      regulation and executive functioning performance compared to boys, and mothers of
      girls reported better emotion regulation abilities compared to mothers of boys.
      These findings add to a nascent literature suggesting that parenting and parental
      emotional functioning may play important roles in children's neurocognitive
      functioning. In addition, they help to explain the mechanisms by which children
      exposed to IPV experience executive functioning deficits.

PMID- 22610835
TI  - Self-protective behaviors and injury in domestic violence situations: does it
      hurt to fight back?
AB  - Research examining the impact of self-protective behaviors on outcomes in
      nonsexual assaults involving intimates has focused solely on one mainstream
      sample (National Crime Victimization Survey) in which violence is a relatively
      rare event. Using the Women's Experience of Violence (WEV) project which collects
      data from a sample of incarcerated women, we explored the phenomenon of self
      protective behaviors to assess whether their use impacts the probability and
      severity of subsequent injury during a domestic violence incident. In addition to
      utilizing a unique sample, we considered an alternative operationalization of
      self-protective behaviors that separates physical and verbal responses to include
      whether the behavior involved an element of force. Results suggest some
      similarities between a mainstream sample and our marginalized sample. Namely, the
      frequency in which they utilize countermeasures and the effect of "fighting back"
      appear to be consistent with previous research. However, the more nuanced
      categorization of self-protective behaviors demonstrates the importance of
      considering whether the strategy was forceful when examining women's responses to
      violence.

PMID- 22610836
TI  - Closing the loop: action research in a multimodal hereditary cancer patient
      conference is an effective tool to assess and address patient needs.
AB  - This paper describes the use of action research in a patient conference to
      provide updated hereditary cancer information, explore patient and family member
      needs and experiences related to genetic cancer risk assessment (GCRA), elicit
      feedback on how to improve the GCRA process, and inform future research efforts.
      Invitees completed GCRA at City of Hope or collaborating facilities and had a
      BRCA mutation or a strong personal or family history of breast cancer. Action
      research activities were facilitated by surveys, round table discussions, and
      reflection time to engage participants, faculty, and researchers in multiple
      cycles of reciprocal feedback. The multimodal action research design effectively
      engaged conference participants to share their experiences, needs, and ideas for
      improvements to the GCRA process. Participants indicated that they highly valued
      the information and resources provided and desired similar future conferences.
      The use of action research in a patient conference is an innovative and effective
      approach to provide health education, elicit experiences, identify and help
      address needs of high-risk patients and their family members, and generate
      research hypotheses. Insights gained yielded valuable feedback to inform clinical
      care, future health services research, and continuing medical education
      activities. These methods may also be effective in other practice settings.

PMID- 22610838
TI  - [Nephron-sparing surgery: our experience].
AB  - OBJECTIVES: To analyze the data of our department with regard to the treatment of
      kidney cancer, with particular attention to nephron-sparing surgery (NSS). Data
      of initial experience on robot-assisted partial nephrectomy (RAPN) were also
      analyzed. METHODS: Between January 2005 and December 2010, at the Urology Clinic
      of Padua, 780 procedures for kidney cancer were performed: 462 radical
      nephrectomies (RN), 289 open partial nephrectomies (OPN), and 29 robot-assisted
      partial nephrectomies (RAPN). Between January 2010 and July 2011 41 RAPN as well
      as 38 OPN were performed. RESULTS: The average volume of tumors treated with RAPN
      was 2.17 cm, 1.98 cm, and 2.78 cm in the first, second, and third half-year,
      respectively. The mean operative time was 220 minutes, 200 minutes, and 180
      minutes in the first, second, and third half-year, respectively. The average warm
      ischemia time was 24 minutes, 22 minutes, and 21 minutes in the first, second,
      and third half-year, respectively. The average estimated blood loss was 170 mL,
      160 mL, and 180 mL in the first, second, and third half-year, respectively. In
      the same period, the average volume of tumors treated with OPN was 3.7 cm, 3.9
      cm, and 5.7 cm respectively in the first, second, and third half-year.
      CONCLUSIONS: We have observed a gradual extension of the indications for NSS. The
      systematic application of robotic surgery has allowed for the treatment of even
      more complex cases with relatively low learning curve. OPN has therefore become a
      technique that should be reserved for more complex cases.

PMID- 22610837
TI  - Sun protection practices among children with a family history of melanoma: a
      pilot study.
AB  - The goal of this pilot study was to assess sun protection practices and
      correlates among children with a family history of melanoma, a high risk and
      understudied group. Sixty-eight melanoma cases, recruited through the Los Angeles
      County cancer registry, completed a survey. Survivors provided data on 110
      children (mean age = 8.11 years). Although most children used sunscreen (79 %),
      half experienced a recent sunburn. The mean sun protection level for the sample
      was similar to levels observed among average risk children. Efforts to reduce
      sunburn frequency and improve sun protection among these vulnerable children
      appear warranted.

PMID- 22610839
TI  - [Impact of preoperative therapy with 5-alpha-reductase inhibitors in the
      treatment of benign prostatic hyperplasia].
AB  - Benign prostatic hyperplasia is considered a progressive disease intimately
      linked with aging. The long-term use of combination therapy with a 5-alpha
      reductase inhibitor, together with an alpha blocker in men with moderate-severe
      symptoms, reduces the risk of clinical progression and BPH-related surgery. It is
      unclear what the impact is of preoperative therapy with 5-ARI in patients that
      undergo surgery. The aim of our study was to evaluate the impact of preoperative
      therapy with 5-alpha-reductase inhibitors on: a) indication on the type of
      surgery; b) surgical and functional outcomes; c) surgical complications. This is
      a prospective observational study. It will include all patients undergoing
      surgery by TURP or Open Prostatectomy in a period of 24 months. We expect results
      that demonstrate significant and favorable influence of pretreatment with 5-alpha
      reductase inhibitors on certain outcomes. Therefore, therapy with 5-ARI could be
      considered as neoadjuvant to surgery, whatever this is.

PMID- 22610840
TI  - [Botulinum toxin type-A toxin activity on prostate cancer cell lines].
AB  - AIM OF THE STUDY: Botulinum toxin A (BoNT/A) has been recently used in the
      treatment of benign prostatic hyperplasia due to its apoptotic activity on
      prostatic epithelium but few data exist on this issue in prostate cancer. Also no
      information exist on the eventual modulation exerted by the neurotoxin on
      Phospholipase A2 (PLA2) expression in prostate cancer. The aim of this study was
      to evaluate the activity of BoNT/A on cell growth and expression of PLA2 in
      prostate cancer lines. MATERIALS AND METHODS: PC-3 and LNCaP cell lines were
      exposed to BoNT/A (Xeomin(r)), different doses and time of exposure. Presence of
      SV2 receptors (SV2-A and SV2-B) for the neurotoxin was also investigated. The
      expression of P-Ser505-cPLA2-alpha (phosphorylated enzyme) was performed
      immunofluorescence. RESULTS: After 96 hours of BoNT/A administration a 20%
      reduction of cell growth in LNCaP and 25% in PC-3 were observed. SV-2 receptors
      were expressed in both cell lines. No cPLA2-alpha total expression was found in
      LnCaP. In PC-3 there was a high expression of cPLA2-alpha total which was not
      modified after BoNT/A treatment. In both LNCap and PC-3 the expression of P
      Ser505-cPLA2-alpha (phosphorylated enzyme) increases significantly after
      treatment with [10 U/ml] of BoNT/A. CONCLUSIONS: LNCaP and PC-3 cell lines are
      sensitive to treatment with BoNT/A which probably enters the cells by SV2
      receptors. The increase in the phosphorylated form of cPLA2-a, induced by BoNT/A
      may represent one mechanism by which the toxin reduces cell growth and
      proliferation.

PMID- 22610841
TI  - [Acetylcholine induces human detrusor muscle cell proliferation: molecular and
      pharmacological characterization].
AB  - INTRODUCTION: The purpose of the study is to understand whether the cholinergic
      stimulation is important, not only in inducing contraction of the detrusor
      muscle, but also in modulating the proliferation of smooth muscle cells. These
      results could help to better understand the role of antimuscarinic drugs, which
      are currently used for the treatment of many urological diseases. PATIENTS AND
      METHODS: Primary cultures were prepared from biopsies of human detrusor muscle of
      subjects >65 years. From the cell culture set-up for each patient, mRNA was
      extracted and both the gene expression and the influence of increasing passages
      on the expression of muscarinic receptor subtypes were evaluated by semi
      quantitative and quantitative PCR (RT-PCR and Q-RT-PCR). The rate of cell
      proliferation induced by cholinergic drugs was assessed by the evaluation of the
      [3H]-thymidine incorporation. RESULTS: The gene expression analysis demonstrated
      that the range of expression of muscarinic subtypes in human detrusor smooth
      muscle cells (HDSMCs) is M2 > M3 > M1 > M4 >> M5. The exposure to the cholinergic
      agonist carbachol induced a concentration-dependent increase in cell
      proliferation rate. The pharmacological characterization indicated that this
      effect was mainly mediated by the receptor subtypes M3 and M2. DISCUSSION: The
      cholinergic stimulation led to an increase in HDSMC proliferation, suggesting
      that this phenomenon might be involved in the pathogenic mechanism through which
      the cervico-urethral obstruction causes a detrusor hypertrophy, followed by a
      loss of function. These results could then provide an indication of the use of
      antimuscarinic drugs in the treatment of lower urinary tract disorders.

PMID- 22610842
TI  - [Relationship between PTH and PSA values in patients with pathological finding of
      benign prostatic hyperplasia].
AB  - The functional relationship between parathyroid glands and prostatic gland is
      commonly very well known. The aim of our study was to investigate the
      relationship between serum levels of PTH and serum levels of PSA in patients with
      pathological finding of BPH. According to 261 transrectal ultrasound-guided
      prostatic biopsies performed from March 2009 to March 2010, 75 patients,
      responding to our inclusion criteria, were selected. 26 patients (34.6%) ended
      the study. All patients with high serum levels of PSA (>4 ng/mL), with
      histological diagnosis of benign prostatic hyperplasia, underwent the assay of
      serum levels of PTH. We observed high levels of PTH (> 66 pg/mL) in 9 patients
      (35.2%).

PMID- 22610843
TI  - The extent of lymphadenectomy does affect cancer specific survival in
      pathologically confirmed T4 renal cell carcinoma.
AB  - BACKGROUND: Controversies exist regarding the effect of lymphadenectomy (LND) in
      renal cell carcinoma (RCC). We hypothesized that patients with locally advanced
      cancer invading beyond Gerota's fascia (pT4 Nany Many RCC) might benefit from an
      extended LND not only for staging but also for survival purposes. MATERIALS AND
      METHODS: Clinical and pathologic data were prospectively gathered in 1.847
      patients treated at a single Academic Center, between 1987 and 2011. Only
      patients with pT4 RCC (TNM 2009, n=44, 2.4%) were included. Univariable (UVA) and
      multivariable (MVA) Cox regression analyses targeted the association between the
      number of lymph nodes removed and cancer specific mortality (CSM). Analyses were
      adjusted for age, Fuhrman grade, symptoms at presentation, metastases at
      diagnosis, ECOG performance status, tumor size, number of positive nodes, and
      presence of necrosis or sarcomatoid features. RESULTS: Mean number of nodes
      removed was 11.8 (median 8, range 1-37). Mean number of positive nodes was 4.8
      (median 2, range 0-36). Cancer-specific survival rates at 1, 2 and 3 years of
      follow-up were 39.3%, 25.0% and 8.6%, respectively. When stratified for nodal
      status, cancer-specific survival rates at 1, 2 and 3 years of follow-up were
      65.0, 36.1, and 9.0% vs. 13.3, 13.0, and 6.7%, for pN0 vs. pN+ cases,
      respectively (p=0.004). At MVA, after adjusting for all the possible confounders,
      the number of positive nodes resulted independently associated with CSM (HR 1.25,
      p=0.001). Interestingly, at MVA, the number of nodes removed achieved the
      independent predictor status, as well (HR 0.84, p=0.007) showing a protective
      effect on survival. The risk of dying increased of 16% every positive node found
      (p<0.001), and decreased of 8% every node removed (p=0.02) (Table II).
      CONCLUSIONS: A more extended retroperitoneal lymphadenectomy at the time of
      nephrectomy statistically significantly decreased CSM in pT4 cases.

PMID- 22610844
TI  - Efficacy of sacral neuromodulation on urological diseases: a multicentric
      research project.
AB  - INTRODUCTION AND AIM OF THE STUDY: Sacral neuromodulation has been used as a
      safe, effective treatment option for patients with lower urinary tract
      dysfunction (LUTD). Several clinical studies demonstrated its positive effects on
      refractory urge incontinence, non-osbstructive urinary retention, urgency
      frequency syndrome, as well as on other non- urological disorders, such as fecal
      incontinence and chronic constipation. The aim of this research project was to
      evaluate the efficacy and safety of sacral neuromodulation on the management of
      LUTD refractory to the standardized first line treatment options. MATERIALS AND
      METHODS: We retrospectively collected and evaluated data from patients undergoing
      sacral neuromodulations between September 2001 and November 2010 in 4 Urological
      Centres of North-East Italy. The patients were affected by Overactive Bladder
      Syndrome (OAB), Urinary Retention (UR), Fecal Incontinence (FI), Constipation
      (CO), Chronic Pelvic Pain (CPP). All the patients were evaluated with voiding
      diaries, before and after implantation.Patients included in the present
      evaluation were followed up in a network of 4 Italian urological centres, which
      participate to in the Italian Clinical Service project - a national urological
      database and medical care project aiming at describing and improving the use of
      implantable urological devices in the Italian clinical practice. Continuous
      normally distributed variables were reported as the mean value +/- standard
      deviation (SD). Continuous non-normally distributed variables were presented as
      the median values and an interquartile range (IQR). The t-test and Wilcoxon test
      were used to compare continuous variables, as appropriate. A two-sided p <0.05
      was considered statistically significant. RESULTS: Overall, 157 patients
      underwent implantation of sacral neuromodulator during the period under review.
      Eighty-three out of 157 (53%) patients complained of OAB; 52 (33%) of UR; 5 (3%)
      of faecal incontinence; 4 (2%) of chronic constipation; 12 (8%) of CPP. The
      median follow- up was 11 months (IQR 1 - 91 months). In patients treated for OAB,
      we documented a statistically significant reduction in the mean number of:
      incontinence episodes/die, pads/die, daily micturitions, nocturnal micturitions
      and global micturitions. In patients treated for UR, we observed a statistically
      significant reduction in the mean post- voiding residual volume and in the number
      of self catheterization. Interpretation of results: It is difficult to translate
      into quantifiable data the subjective perception of improvement of the symptoms
      expressed by the patients, as they are frequently subjective perceptions, not
      always numeric data. This subjective perception makes it difficult to the
      clinician to evaluate the real outcomes of this procedure, and makes it difficult
      to achieve a complete follow-up. CONCLUSIONS: This multicenter research project
      confirmed the midterm safety and effectiveness of sacral neuromodulation in the
      treatment of refractory overactive bladder syndrome and urinary retention,
      showing high cure rates and low complication rates.

PMID- 22610845
TI  - Laparoscopic management of sacral neurinoma causing hydronephrosis.
AB  - We report the case of a sacral neurinoma, which presented with mild
      hydronephrosis, due to compression of the right ureter, in a 71-yr old woman
      admitted to our hospital with recurrent urinary tract infections. CT and MRI
      detected a 4 x 4 cm mass pressing on the right ureter at the sacral level, in
      continuity with the second sacral foramen. Given this finding, the mass was
      thought to be of presumable neurogenic origin. In order to both reach a
      conclusive diagnosis and relieve the compression of the ureter, a laparoscopic
      resection of the mass was performed. Surgery was successful and the pathologic
      examination revealed a sacral Antoni A neurinoma. Neurinomas, also called
      Schwannomas, are uncommon benign nerve sheath tumors arising from Schwann cells.
      Their diagnosis can be extremely difficult due to their aspecific symptoms and
      the lack of pathognomonic characteristics on imaging exams. Therefore,
      histopathologic evaluation is essential in establishing the diagnosis. Surgical
      resection seems to be the best approach, both for diagnostic and therapeutic
      purposes.

PMID- 22610846
TI  - Intraoperative transesophageal echocardiography diagnosis of rare source of right
      ventricular failure after heart transplant.

PMID- 22610847
TI  - A stenotic bioprosthetic valve in the tricuspid position: real-time 3-dimensional
      transesophageal echocardiography as a useful supplement to conventional
      assessment.

PMID- 22610848
TI  - Lack of value of scheduling processes to move cases from a heavily used main
      campus to other facilities within a health care system.
AB  - BACKGROUND: Economically, the most important anesthesia group and operating room
      (OR) management decision is the choice made months before surgery of the
      allocated OR time (duration of the workday) for each service. Consider a health
      system with surgeons who practice at multiple hospitals and ambulatory surgery
      centers. The main campus' ORs are busy, with nearly 8 h of cases, including
      turnovers, per anesthetizing location per workday. The other (regional)
      facilities have substantial underutilized time. A surgeon wants to do one 3-hour
      case at the main campus and have an afternoon start. The anesthesia group's OR
      director could use the health systems' common OR information system to examine
      the surgeons' schedules at all facilities. In this study, we quantify the
      percentage of OR hours that can practically be off-loaded from a main campus with
      long duration workdays. METHODS: One year of cases were evaluated from a health
      system with a busy main campus, multiple (11) regional facilities with low
      workload per OR per day, and a common OR information system. RESULTS: The OR time
      was summed among surgeons meeting the following criteria: no first case start at
      the main campus that day; performing <4 hour of elective cases at the main campus
      that day; and doing at least 1 case at any of the regional facilities within the
      preceding or following week. The OR time potentially moveable was <0.8% (95% CI,
      0.7% to 0.8%) of the total OR time used by all surgeons operating at the main
      campus, considerably less than the managerially important threshold of ">= 5.0%"
      (P < 0.0001). The principal reason for the result was that few (10%) OR hours at
      the main campus were used by surgeons performing <4 hour of cases that day. To
      understand why so little OR time could be moved, we performed secondary analysis
      of different data from 21 facilities nationwide. Larger hours of cases per OR per
      workday (e.g., 7.8 hour at the main facility) were commonly associated with
      larger percentages of workdays for which single surgeons filled an OR for the day
      (r = 0.87 +/- 0.05). CONCLUSIONS: For many health systems, investing in the
      software and personnel to coordinate case scheduling among facilities is unlikely
      to be of benefit, either operationally or financially.

PMID- 22610849
TI  - Measure to quantify the influence of time from end of surgery to tracheal
      extubation on operating room workflow.
AB  - BACKGROUND: The impact of delays in extubation on operating room (OR) workflow
      are challenging to assess because such delays may or may not be a bottleneck to
      the patient leaving the OR. We developed an observational measure that quantifies
      the influence of extubation times on OR workflow. METHODS: The time from dressing
      on the patient (or its functional equivalent) to tracheal extubation was observed
      in ORs, among a cohort of adult patients undergoing elective (scheduled) general
      anesthesia. During the first 36 extubations, the measure was developed using
      qualitative methods. During the subsequent 64 extubations, qualitative
      observation was supplemented with quantitative measurement. Interrater
      reliability was assessed during the final 30 of the 64 extubations. Video 1 (see
      Supplemental Digital Content 1, http://links.lww.com/AA/A396) shows animation of
      a typical observation period. RESULTS: The developed measure was a single value
      for each case: whether at least 1 person was doing no visible physical activity
      potentially related to patient care for at least 1 minute between dressing on the
      patient and tracheal extubation. Assessing reliability, 2 raters' listings of
      cases with no versus 1 or more people idle were identical for 30 of 30 cases (95%
      lower confidence limit >90%). Spearman r = 0.99 (95% lower confidence limit 0.99)
      for time from dressing on patient to extubation. Predictive validity was shown by
      positive correlation between the percentage of cases with at least 1 person idle
      and extubation time (P < 0.0001): 21% for <5 minutes, 42% for 5 to 10 minutes,
      87% for 10 to 15 minutes, and 100% for >15 minutes. DISCUSSION: Longer times to
      extubation are associated with an increased chance of at least 1 person waiting
      in the OR. This measure can be used in observational studies and for lean
      engineering projects to assess conditions when time to extubation affects
      workflow. Observers can combine use of this measure for extubation times with the
      previously developed measure for studying the influence of induction times on OR
      workflow.

PMID- 22610851
TI  - Autosomal recessive lethal congenital contractural syndrome type 4 (LCCS4) caused
      by a mutation in MYBPC1.
AB  - Autosomal recessive lethal congenital contractural syndrome (LCCS) is a severe
      form of neuromuscular arthrogryposis. We previously showed that this phenotype is
      caused in two unrelated inbred Bedouin tribes by different defects in the
      phosphatidylinositol pathway. However, the molecular basis of the same phenotype
      in other tribes remained elusive. Whole exome sequencing identified a novel LCCS
      founder mutation within a minimal shared homozygosity locus of approximately 1 Mb
      in two affected individuals of different tribes: a homozygous premature stop
      producing mutation in MYBPC1, encoding myosin-binding protein C, slow type. A
      dominant missense mutation in MYBPC1 was previously shown to cause mild distal
      arthrogryposis. We now show that a recessive mutation abrogating all functional
      domains in the same gene leads to LCCS.

PMID- 22610850
TI  - Novel small molecule alpha9alpha10 nicotinic receptor antagonist prevents and
      reverses chemotherapy-evoked neuropathic pain in rats.
AB  - BACKGROUND: Peripheral neuropathy is a common dose-limiting side effect of
      chemotherapy. There are no clinically proven analgesics for the treatment of this
      condition. Drugs from different classes have been tested with mixed results.
      Identification of novel molecular targets for analgesic(s) is important.
      Antagonism of the alpha9alpha10 nicotinic acetylcholine receptor (nAChR) subtype
      (absent in brain) is thought to underlie analgesic efficacy of peptide alpha
      conotoxins. We found novel nonpeptide small molecule analogs from a family of
      tetrakis-, tris-, and bis-azaaromatic quaternary ammonium salts (high potency
      with selectivity as antagonists at the alpha9alpha10 nAChRs) to produce dose
      related analgesia in rat models of nerve injury-evoked neuropathy and persistent
      inflammatory pain. No tests were done in a model of neuropathy induced by drug
      administration (ie, chemotherapy). METHODS: In this study, a lead bis-analog, ZZ1
      61c, was characterized in a rat model of vincristine-evoked neuropathy. Male
      Sprague-Dawley rats were repeatedly dosed with the vinca-alkaloid, vincristine
      (100 MUg/kg/day IP, days 1 to 5 and 8 to 12). ZZ1-61c (100 MUg/kg/day IP) was
      given either along with or after completion of vincristine (commencing by day 15
      when neuropathy was maximum). Responsiveness was assessed with von Frey hairs and
      the paw-pressure test. The effects of ZZ1-61c on motor function (rotarod) and
      muscle strength (grip test) were characterized in naive rats. RESULTS: The
      development of neuropathy was demonstrated with repeated dosing of vincristine
      (pain hypersensitivity in response to mechanical stimulation). ZZ1-61c showed
      both preventive and restorative effects on this condition: (1) vincristine-evoked
      sensitivity to pressure was reduced by coadministration of ZZ1-61c; (2)
      established neuropathy was diminished by ZZ1-61c after cessation of chemotherapy.
      ZZ1-61c did not cause motor dysfunction (rotarod) or muscular weakness (the grip
      test). CONCLUSIONS: This study suggests that ZZ1-61c, a novel compound with a
      unique mechanism of antagonistic action at the alpha9alpha10 nAChR, may be a
      potential drug candidate for prevention and attenuation of neuropathic pain
      resulting from chemotherapy. Such a strategy may provide effective treatment that
      circumvents toxicity of centrally acting agonists at nAChR.

PMID- 22610852
TI  - Clinico-genetic aspects of a pediatric non-neurofibromatosis type 1 malignant
      triton tumor with loss of chromosome X.
AB  - Malignant triton tumor (MTT) is an aggressive peripheral nerve sheath tumor with
      rhabdomyoblastic differentiation. Less than 100 cases have been described, being
      mostly male children with type 1 neurofibromatosis. We report a 6-year-old female
      with MTT and no diagnostic criteria for neurofibromatosis type 1. Cytogenetic
      analysis showed a 46,X,-X[4]/46,XX[16] karyotype. She underwent a transfemoral
      amputation and chemotherapy and is free of disease 15 months after diagnosis. The
      few cytogenetic studies of MTT described in the literature have been
      inconclusive. Further cytogenetic analyses are needed to understand the role of
      chromosome X monosomy in the pathogenesis of this rare tumor.

PMID- 22610853
TI  - Effects of supplementation with curcuminoids on dyslipidemia in obese patients: a
      randomized crossover trial.
AB  - Dyslipidemia is a leading risk factor for cardiovascular disease and is also a
      common feature of obesity. Curcumin is a bioactive phytochemical with well-known
      antioxidant, anti-inflammatory, and cardioprotective properties. The present
      study investigated the hypolipidemic activity of curcumin in obese individuals.
      Participants (n = 30) were treated with curcuminoids (1 g/day), or placebo in a
      randomized, double-blind, placebo-controlled, crossover trial. Serum
      concentrations of total cholesterol, triglycerides, low-density lipoprotein
      cholesterol and high-density lipoprotein cholesterol, together with
      anthropometric parameters and high-sensitivity C-reactive protein were measured
      before and after each treatment period. Anthropometric parameters including
      weight, BMI, waist circumference, hip circumference, arm circumference, and body
      fat remained statistically unchanged by the end of trial (p > 0.05). As for the
      lipid profile parameters, serum triglycerides were significantly reduced
      following curcumin supplementation (p = 0.009). However, curcuminoids were not
      found to affect serum levels of total cholesterol, low-density lipoprotein
      cholesterol, high-density lipoprotein cholesterol, and high-sensitivity C
      reactive protein (p > 0.05). In summary, the findings of the present study
      indicated that curcuminoid supplementation (1 g/day for 30 days) leads to a
      significant reduction in serum triglycerides concentrations but do not have a
      significant influence on other lipid profile parameters as well as body mass
      index and body fat.

PMID- 22610854
TI  - Immune epitope database analysis resource.
AB  - The immune epitope database analysis resource (IEDB-AR: http://tools.iedb.org) is
      a collection of tools for prediction and analysis of molecular targets of T- and
      B-cell immune responses (i.e. epitopes). Since its last publication in the NAR
      webserver issue in 2008, a new generation of peptide:MHC binding and T-cell
      epitope predictive tools have been added. As validated by different labs and in
      the first international competition for predicting peptide:MHC-I binding, their
      predictive performances have improved considerably. In addition, a new B-cell
      epitope prediction tool was added, and the homology mapping tool was updated to
      enable mapping of discontinuous epitopes onto 3D structures. Furthermore, to
      serve a wider range of users, the number of ways in which IEDB-AR can be accessed
      has been expanded. Specifically, the predictive tools can be programmatically
      accessed using a web interface and can also be downloaded as software packages.

PMID- 22610856
TI  - GENIES: gene network inference engine based on supervised analysis.
AB  - Gene network inference engine based on supervised analysis (GENIES) is a web
      server to predict unknown part of gene network from various types of genome-wide
      data in the framework of supervised network inference. The originality of GENIES
      lies in the construction of a predictive model using partially known network
      information and in the integration of heterogeneous data with kernel methods. The
      GENIES server accepts any 'profiles' of genes or proteins (e.g. gene expression
      profiles, protein subcellular localization profiles and phylogenetic profiles) or
      pre-calculated gene-gene similarity matrices (or 'kernels') in the tab-delimited
      file format. As a training data set to learn a predictive model, the users can
      choose either known molecular network information in the KEGG PATHWAY database or
      their own gene network data. The user can also select an algorithm of supervised
      network inference, choose various parameters in the method, and control the
      weights of heterogeneous data integration. The server provides the list of newly
      predicted gene pairs, maps the predicted gene pairs onto the associated pathway
      diagrams in KEGG PATHWAY and indicates candidate genes for missing enzymes in
      organism-specific metabolic pathways. GENIES (http://www.genome.jp/tools/genies/)
      is publicly available as one of the genome analysis tools in GenomeNet.

PMID- 22610855
TI  - Inferring direct DNA binding from ChIP-seq.
AB  - Genome-wide binding data from transcription factor ChIP-seq experiments is the
      best source of information for inferring the relative DNA-binding affinity of
      these proteins in vivo. However, standard motif enrichment analysis and motif
      discovery approaches sometimes fail to correctly identify the binding motif for
      the ChIP-ed factor. To overcome this problem, we propose 'central motif
      enrichment analysis' (CMEA), which is based on the observation that the
      positional distribution of binding sites matching the direct-binding motif tends
      to be unimodal, well centered and maximal in the precise center of the ChIP-seq
      peak regions. We describe a novel visualization and statistical analysis tool-
      CentriMo--that identifies the region of maximum central enrichment in a set of
      ChIP-seq peak regions and displays the positional distributions of predicted
      sites. Using CentriMo for motif enrichment analysis, we provide evidence that one
      transcription factor (Nanog) has different binding affinity in vivo than in
      vitro, that another binds DNA cooperatively (E2f1), and confirm the in vivo
      affinity of NFIC, rescuing a difficult ChIP-seq data set. In another data set,
      CentriMo strongly suggests that there is no evidence of direct DNA binding by the
      ChIP-ed factor (Smad1). CentriMo is now part of the MEME Suite software package
      available at http://meme.nbcr.net. All data and output files presented here are
      available at: http://research.imb.uq.edu.au/t.bailey/sd/Bailey2011a.

PMID- 22610858
TI  - Neurocysticercosis in Nepal and it's global perspective.

PMID- 22610859
TI  - Incidence of incidental carcinoma gall bladder in cases of routine
      cholecystectomy.
AB  - BACKGROUND: Carcinoma of gall bladder is the most common malignancy of the
      billiary tract. Most of the cases are diagnosed as an incidental case among
      patients undergoing cholecystectomy. OBJECTIVES: To establish the rate of
      incidental carcinoma of gall bladder in patients undergoing routine
      cholecystectomy to study the demographic profile and prognosis of these patients.
      METHODS: A retrospective study was carried out in Fishtail Hospital and Research
      Center, Pokhara during 1998-2009. The surgical notes, hospital records and
      histopathology reports of 783 patients undergoing routine cholecystectomy were
      studied. RESULTS: Out of 783 cases, gall bladder cancer was detected in 10(1.28%)
      of cases and was more common in females (M:F ratio 1:2.3) and the mean age of
      occurrence was 63.8 years. Most of the cases diagnosed were at their early stages
      and none of them were in T3 and T4 stages. Six of these patients have survived
      till a mean follow up duration of 23.7 months. CONCLUSION: The rate of incidental
      carcinoma of gall bladder is 1.28%.

PMID- 22610857
TI  - Crystal structure and mechanism of action of the N6-methyladenine-dependent type
      IIM restriction endonuclease R.DpnI.
AB  - DNA methylation-dependent restriction enzymes have many applications in genetic
      engineering and in the analysis of the epigenetic state of eukaryotic genomes.
      Nevertheless, high-resolution structures have not yet been reported, and
      therefore mechanisms of DNA methylation-dependent cleavage are not understood.
      Here, we present a biochemical analysis and high-resolution DNA co-crystal
      structure of the N(6)-methyladenine (m6A)-dependent restriction enzyme R.DpnI.
      Our data show that R.DpnI consists of an N-terminal catalytic PD-(D/E)XK domain
      and a C-terminal winged helix (wH) domain. Surprisingly, both domains bind DNA in
      a sequence- and methylation-sensitive manner. The crystal contains R.DpnI with
      fully methylated target DNA bound to the wH domain, but distant from the
      catalytic domain. Independent readout of DNA sequence and methylation by the two
      domains might contribute to R.DpnI specificity or could help the monomeric enzyme
      to cut the second strand after introducing a nick.

PMID- 22610860
TI  - Triiodothyronin, thyroxine and thyrotropin in vitiligo.
AB  - BACKGROUND: Vitiligo is a common pigmentary disorder of the skin, affecting
      individuals globally. Not only is this ailment psychologically incapacitating, it
      also has a high incidence of autoimmunity, signifying that its manifestations may
      be the portrayal of dysfunction of immune system. OBJECTIVE: The aim of this
      study is to find out the situations of abnormal thyroid function test (TFT) in
      vitiligo patients. METHODS: A prospective cross sectional study was conducted at
      the Dhulikhel Hospital, KUTH, Dhulikhel during November 2008 to January 2011 with
      the objective to assess the thyroid function tests in vitiligo patients. RESULTS:
      Total 66 vitiligo patients with male 30 (45%) and female 36 (55%). Total 26
      (39.39%) vitiligo patients have been found to have abnormal thyroid function
      test. Among them 10 had abnormal T3, seven had abnormal T4 and 12 had abnormal
      TSH level. Thyroid function test were normal in other vitiligo patients. Total
      seven vitiligo had high level of T3 than normal value, four male and three
      female. Two had higher level of T4 above 2.0 ng/dl and all were male, while five
      had abnormally low level of T4 with three male and two female. There were seven
      vitiligo patient with increased T3 level and three with decreased T3 level, among
      them six were males and four were females, the age group was ranged from seven to
      68 years old. The T4 level were found abnormal in seven vitiligo patients among
      which five were males and two were females with the age group ranging from 7 to
      51 years. CONCLUSIONS: There has been significant association of thyroid disorder
      in the patient with vitiligo. Therefore, patient with vitiligo need to undergo
      thyroid function test to rule out the thyroid disorder and prevent from long-term
      complications.

PMID- 22610861
TI  - Ipsilateral supracondylar fracture and forearm bone injury in children: a
      retrospective review of thirty one cases.
AB  - BACKGROUND: Pediatric supracondylar fracture and forearm bone fracture is common
      in isolation but combined supracondylar fracture with ipsilateral forearm bone
      fracture, known as floating elbow is not common injury. The incidence of this
      association varies between 3% and 13%. Since the injury is rare and only limited
      literatures are available, choosing best management options for floating elbow is
      challenging. METHOD: In retrospective review of 759 consecutive supracondylar
      fracture managed in between July 2005 to June 2011, children with combined
      supracondylar fracture with forearm bone injuries were identified and their
      demographic profiles, mode of injury, fracture types, treatment procedures,
      outcome and complications were analyzed. RESULT: Thirty one patients (mean age
      8.91 yrs, range 2-14 yrs; male 26; left side 18) had combined supracondylar
      fracture and ipsilateral forearm bone injury including four open fractures. There
      were 20 (64.51%) Gartland type III (13 type IIIA and 7 type III B), seven (22.58
      %) type II, three (9.67 %) type I and one (3.22 %) flexion type supracondylar
      fracture. Nine patients had distal radius fracture, six had distal third both
      bone fracture, three had distal ulna fracture, two had mid shaft both bone injury
      and one with segmental ulna with distal radius fracture. There were Monteggia
      fracture dislocation, proximal ulna fracture, olecranon process fracture,
      undisplaced radial head fracture of one each and two undisplaced coronoid process
      fracture. Displaced forearm fracture required closed reduction and fixation with
      Kirschner wires or intramedullary nailing. Nineteen patients with Gartland type
      III fracture underwent operative intervention. Among them nine had closed
      reduction and K wire fixation for both supracondylar fracture and forearm bone
      injury. There were three radial nerve, one ulnar nerve and one median nerve
      injury and two postoperative ulnar nerve palsy. Three patients had pin tract
      related complications. Among type III, 16 (80%) patients had good to excellent,
      two had fair and one had poor result in terms of Flynn criteria in three months
      follow up. CONCLUSION: Displaced supracondylar fracture with ipsilateral
      displaced forearm bone injuries need early operative management in the form of
      closed reduction and percutaneous pinning which provides not only stable fixation
      but also allows close observation for early sign and symptom of development of
      any compartment syndrome.

PMID- 22610862
TI  - Variability of presentations and CT-scan findings in children with
      neurocysticercosis.
AB  - BACKGROUND: Neurocysticercosis is one of the common neurological morbidities in
      childhood. OBJECTIVES: To find the commonest mode of presentation of this
      disorder in children. The study also aims to find out the age at which it
      commonly occurs, commonest site affected in the brain and the ethnic group and
      region most commonly affected in Western Nepal. METHODS: Retrospective hospital
      based study carried out in the Department of Pediatrics, Manipal Teaching
      Hospital, Pokhara from June 2004 to June 2009. RESULTS: Over the period of five
      years, 678 patients were admitted for seizures; out of which 109 patients were
      diagnosed as having neurocysticercosis (16%). Out of them, 66 (60.5%) were males
      and 43 (39.4%) were females. The age of presentation varied from 18 months to 16
      years, with mean age 9.77 years. The most common age of presentation was between
      6-10 years (n=47; 43.1%) and 11-15 years (n=47; 43.1%). Maximum number of
      patients were from Kaski district (n=41; 37.6%) followed by Syangja (n=34;
      31.1%).The commonest presentation was with seizures (n=85; 77.9 %); generalised
      seizures was present in 45 patients (52%). Psychiatric manifestations were
      present in 3 patients (2.7%). The lesions were found mostly in the parietal
      region (n=65; 59.6 %). Most of the lesions were single (n=89; 81.6%). Out of 109
      patients, 74 patients (67.8%) improved without any recurrence of symptoms on two
      years follow-up. CONCLUSION: Neurocysticercosis is a preventable zoonotic disease
      which results in significant morbidity in children where sanitary measures are
      inadequate. Any child presenting with a first episode, afebrile seizure should be
      screened for neurocysticercosis provided other common causes are ruled out.

PMID- 22610863
TI  - The glucose challenge test for screening of gestational diabetes.
AB  - BACKGROUND: The frequency of gestational diabetes mellitus (GDM) is 0.6% -15% of
      pregnant woman. The modern trend towards the delay starting family is the main
      factor responsible for increase prevalence of GDM. This condition is associated
      with the adverse effect on mother and fetus, so it is important to find out the
      GDM by screening of all the pregnant women. OBJECTIVE: To observe the feasibility
      of using the 50g GCT for all pregnant women attending Dhulikhel Hospital,
      Obstetric OPD. To determine the incidence of gestational diabetes in the
      population and to observe the maternal and fetal outcome among those having an
      elevated GCT level and gestational diabetes. METHODS: A prospective and
      analytical study of 1598 pregnant women booked and delivered between June 2009and
      August 2010. Glucose challenge test (GCT) performed by using 50gm glucose and
      diagnosis of gestational diabetes performed by using the Carpenter Coustan
      Criteria. Pregnancy outcomes were assessed by the gestation and mode of delivery.
      Similarly, neonatal outcomes assessed in terms of birth weights, APGAR scores,
      congenital abnormalities, hyperbilirubinaemia, hypoglycaemia or respiratory
      distress syndrome. RESULTS: The detected incidence of gestational diabetes was
      0.75%. With the threshold plasma glucose level at140 mg/ dl, 198 women needed to
      undergo the 100g oral glucose tolerance test and 12 women had gestational
      diabetes. The diagnostic yield was 6.06%. Perinatal outcome was similar to the
      rest of the women with normal glucose challenge test. CONCLUSIONS: The 50g GCT is
      feasible and also helps to find out GDM. It is easy, user friendly, cheap and
      convenient for screening purpose.

PMID- 22610864
TI  - The burden of injury in terms of economics loss and disability days: a community
      based study form eastern Nepal.
AB  - BACKGROUND: Injuries are already a substantial public Health problem all over the
      world and are expected to increase in the 211st Century. They are major causes of
      deaths and disability in the population and also involve high societal costs.
      OBJECTIVES: This study was designed to assess the economic loss due to the injury
      and the disability days due to different types of injuries. METHODS: A systematic
      random sampling technique was used to select 1388 households from 19 wards. A
      detailed questionnaire was used to collect information related to injuries to the
      persons suffered from injuries including treatment obtained, cost of treatment
      (direct/indirect cost) and length of disability. RESULTS: Among the minor injured
      persons, majority (93.2%) did not spend any indirect cost. 36.7% of the major
      inured persons spent Nepalese rupees 10,001 to NRs 100,000 as direct treatment
      costs. But 50% spent less than 5000 NRs as indirect cost for major injury
      treatment. Maximum number (67.4%) of major injured persons had disability days of
      31 to 90 days. CONCLUSION: The high incidence of injuries, especially road
      traffic injuries, adds a huge economic burden to nation.

PMID- 22610865
TI  - Pattern of organophosphorous poisoning: a retrospective community based study.
AB  - BACKGROUND: Pesticide poisoning is very common in Nepal. Hospital based studies
      from various parts of Nepal have shown that poisoning with organophosphorus
      compounds is the most common type of poisoning. Current study is undertaken to
      see the pattern of organophosphorus poisoning and to identify the common risk
      factors among the cases. If the risk factors are modifiable, attempts in
      addressing the risk factors and decreasing the likelihood of poisoning will
      certainly be fruitful in reducing the morbidity and mortality associated with
      organophosphorus poisoning. OBJECTIVES: To assess the risk factors of
      organophosphorus poisoning which is major public health problem in Nepal.
      METHODS: A community based retrospective study of 75 cases of organophosphate
      poisoning who were brought to the emergency department of Dhulikhel hospital over
      the period of 3 years. Basic information was collected from hospital records and
      home visits were made to study the risk factors. Data were collected through
      interviews of the study population and their family members using a pre-designed
      questionnaire. RESULTS: In this study 75 cases and their families were
      interviewed of which there were 59% males and 42% females (M/F ratio of 1:1.4).
      The majority (40%) of the poisoning cases were in the age group 25-34 years.
      Lower literacy level showed positive association with the incidence of poisoning.
      Occupation wise vast majority (80%) of the cases were engaged in agricultural
      work. Suicidal attempts by ingesting organophosphate compounds were high in
      farmers and females. CONCLUSION: In this study, majority of the poisoning were
      attempts of intentional self harm. Agriculture workers and females are high risk
      groups and may be associated with the fact that they have easy access to the
      poison. Interventions directed towards health education, counseling, and
      enforcement of laws restricting the availability and use of harmful pesticides
      may help in reducing such events in future.

PMID- 22610866
TI  - Haemolytic effects of hypo-osmotic salt solutions on human erythrocytes.
AB  - BACKGROUND: While it is well known that hypotonic solutions of sodium chloride
      induce hemolysis, the effects of other salt solutions on human erythrocytes have
      not been well documented. OBJECTIVE: The study is to compare the effects of other
      salt solutions on human red cells. METHODS: Iso-osmotic and hypo-osmotic
      solutions of various salts were prepared after taking into account their
      molecular weight and osmotic pressure. Five healthy volunteers between the age of
      22-30 years were randomly selected and ten blood samples were collected from
      them. The study was conducted from January 2009 to February 2009. Blood was
      collected from subjects by venepuncture into heparinised tubes. 20 fl of blood
      was pipetted into 1 ml of each solution and incubated for one hour at 37 degrees
      C in a water bath. The solutions were centrifuged and the colour of the
      supernatant was read in a spectrophotometer. Supernatant from blood added to
      distilled water was considered 100% hemolysed. RESULTS: Iso-osmotic salt
      solutions were free of hemolysis. Among chloride salts, sodium chloride showed
      the least hemolysis and potassium chloride and nickel chloride resulted into
      greater hemolysis. Among potassium salts, potassium bromate caused highest amount
      of hemolysis whereas potassium sulphate showed the least. CONCLUSION: The
      significant differences in hemolytic pattern in hypo-osmotic salts solutions
      suggest that the hypo-osmotic stress causes morphological changes in red cells
      that alter their permeability to various ions leading to hemolysis. This probably
      occurs through opening of volume sensitive channels.

PMID- 22610867
TI  - Incidence of hypertension in patients undergoing surgery at Dhulikhel Hospital
      Kathmandu University Hospital.
AB  - BACKGROUND: Hypertension is an important public health challenge worldwide and is
      most important modifiable risk factor for cardiovascular, cerebrovascular and
      renal disease. Blood pressure determination forms an integral part of
      anaesthesiologist evaluation of his patient condition prior to and during
      surgery. Data are not available which indicate changes in blood pressure
      occurring preanaesthetically in hospitalized patients. There are several risks
      from untreated preoperative hypertension in perioperative and postoperative
      phase. OBJECTIVE: To know the incidence of hypertension in preoperative patients
      undergoing major surgery. METHODS: This retrospective observational study was
      based on the data collected from preanaesthetic checkup record book from January
      2010 to December 2010. RESULTS: A total of 955 patients were studied and analyzed
      in terms of hypertension and demographic characteristics. The total incidence of
      hypertension in preoperative phase was 10.16%. Among them 64.9% being male and
      35.1% female. Maximum incidence was found in age group 50-59 years i.e. 26.6%.
      Among the case detected maximum patients i.e. 52% were patients with newly
      diagnosed hypertension and among those under medications 61.1% were using calcium
      channel blockers. CONCLUSION: Knowing the incidence will help in proper
      preoperative optimization of the hypertensive patients and also help in
      decreasing the incidence of postoperative complications.

PMID- 22610868
TI  - Prevalence of sexually transmitted infections in a tertiary care centre.
AB  - BACKGROUND: The burden of sexually transmitted infections is huge and is
      disproportionately affecting developing nations. In Nepal, recent available data
      on sexually transmitted infections are mostly targeted to high risk population. A
      prevalence study was thus done to explore the pattern of sexually transmitted
      infection syndromes among general population of Nepal. OBJECTIVES: To highlight
      the prevalence and changing pattern of sexually transmitted infections among
      general population. METHODS: A retrospective study. The study was conducted among
      145 patients attending Department of Dermatology and Venerology, Dhulikhel
      Hospital Kathmandu University Hospital, for voluntary counseling and testing from
      April 2010 to April 2011. Syndromic case management approach was used for the
      classification and treatment of the patients. RESULTS: 106 patients were
      suffering from Sexually Transmitted Infections and 2 patients were positive for
      Human Immunodeficiency Virus. The most common diagnosis was genital viral
      infections (41.7%). Prevalence was highest among drivers/conductors (26.9%) and
      migrating workers (23.1%). Age group 20 to 24 years was the maximum sufferers
      (37%). Unsafe sexual activity (66.7%) was the most potential exposure and
      majority of the patients were not consistent in using condom. CONCLUSIONS:
      Genital viral infections constitute the major bulk of sexually transmitted
      infections. Majority of the patients suffering from sexually transmitted
      infections were in the age group 20 to 24 years and were mostly drivers,
      conductors or migrating workers by occupation. In the background of few available
      baseline data, the results are expected to assist successful target interventions
      in the near future.

PMID- 22610869
TI  - Sonographic measurement of fetal pinna length in normal pregnancies.
AB  - BACKGROUND: Many studies have emphasized on fetal pinna measurements and
      morphologic features to use this structure as an additional marker for fetal
      chromosomal anomaly. OBJECTIVES: To assess relationship between fetal pinna
      length and gestation age and develop a nomogram. To assess relationship between
      fetal pinna length and head circumference and biparietal diameter. METHODS: Fetal
      pinna measurements from the tip of helix to the end of lobe were obtained
      prospectively in 850 singleton pregnant women between 15 and 40 weeks gestation
      Normal case was defined as normal sonographic findings during examination and
      normal infant examination at birth or both. Final study population was 787. The
      relationship between gestational age in weeks to pinna length in millimeters was
      analyzed by simple linear regression. Correlation of fetal ear length
      measurements with gestational age, biparietal diameter and head circumference
      were also obtained. RESULTS: Linear relationships were found between fetal pinna
      length and gestational age [Pinna Length (mm)=1.044xGestational age (weeks) 
      3.857]. A nomogram of normal pinna length was obtained. High correlation was
      found between pinna length and gestational age (r=0.942; p less than 0.001),
      pinna length and head circumference (r=0.931; p less than 0.001). Significant
      correlation was found between pinna length and biparietal diameter (r=0.934;
      p=0.004) CONCLUSIONS: The results of this study provide a nomogram for fetal
      pinna. The study also provides relationship and good correlation between pinna
      length and other biometric measurements.

PMID- 22610870
TI  - Correlation of calcium, phosphorus, uric acid and magnesium level in serum and 24
      hours urine of patients with urolithiasis.
AB  - BAKCGROUND: Urinary stones disease is common pathology encountered in urological
      practice in Nepal. Supersaturated urine and its stagnation are well known facts
      for the development of urolithiasis. Metabolic disorders like hypercalciuria,
      hyperuricaemia, hypocitraturia are also responsible for formation of
      urolithiasis. OBJECTIVE: The aim of this study was to identify the level of
      calcium, phosphorus, uric acid, and magnesium in the blood and urine of Nepalese
      patients with urinary stones. METHODS: This study was conducted over a period of
      six months (From May to November 2010). It is a descriptive cross sectional study
      and quantitative method was used for analysis. Primary data were collected and
      utilized from 79 cases. RESULTS: The prevalence of urolithiasis in male patients
      was 65.8% and 34.2% in female patients (p less than 0.05). Serum calcium in stone
      former and non-stone former was 8.3+/-1.2 and 7.5+/-1.5 (p less than 0.01)
      respectively. Serum phosphorus and uric acid in both groups were statistically
      not significant (p value 0.269 and 0.597 respectively) though in 24 hours urine
      of stone formers value of phosphorus was 447.9+/-182.4 but in non-stone formers
      it was 186.5+/-118.7 (p less than 0.001). Magnesium level in urine was 48.1+/
      69.7 and 131.4+/-86.9 (p less than 0.001) respectively. CONCLUSION: Higher level
      of calcium in serum was found in patients with urolithiasis in our population.
      Though phosphate level in blood serum was not different in the both groups but in
      urine phosphate and magnesium levels were significantly different.

PMID- 22610871
TI  - Antenatal care practices in Tamang community of hilly area in central Nepal.
AB  - BACKGROUND: Antenatal care is provided during pregnancy to save lives of mother
      and foetus. World Health Organization recommends four focused visits as
      sufficient for normal pregnancy. OBJECTIVE: The objective of the study was to
      find out antenatal care practices in Tamang community of hilly areas of central
      Nepal. METHODS: Descriptive cross-sectional study was conducted in Tamang
      community of Lalitpur district. Systematic random sampling method was used to
      collect data from April to May 2011. Data of 194 women having >= 3 years of
      children was collected and analyzed in descriptive and inferential ways. RESULTS:
      Antenatal visits were made by 78.9% (153) of women but only 46.4% (71) completed
      four antenatal visits. Mean visit was of 3.5 +/- 1.13 times. Ninety four (61.4%)
      of first antenatal visits attainders completed the fourth visit. Age of women and
      antenatal visits, taking tetanus toxoid injection and knowledge on work of iron
      tablets exhibited significant association at 95% level of confidence (p less than
      0.05). There was also significant association between numbers of childbirth and
      antenatal visits at 95% level of confidence (p less than 0.05). CONCLUSIONS:
      There was a high rate of early marriage and early pregnancy in the Tamang
      communities. Women did not place high importance on antenatal visits. A large
      percentage did not complete all four recommended antenatal visits. Use of
      necessary medicine like iron, albendazole tablets and tetanus toxoid injection
      was often incomplete.

PMID- 22610872
TI  - Minimally invasive plate osteosynthesis  with locking compression plate for
      distal diametaphyseal tibia fracture.
AB  - BACKGROUND: Distal diametaphyseal tibia fracture though requires operative
      treatment is difficult to manage. Conventional osteosynthesis is not suitable
      because distal tibia is subcutaneous bone with poor vascularity. Closed reduction
      and minimally invasive plate osteosynthesis (MIPO) with locking compression plate
      (LCP) has emerged as an alternative treatment option because it respects biology
      of distal tibia and fracture hematoma and also provides biomechanicaly stable
      construct. OBJECTIVES: To find out suitability of MIPO with LCP for distal
      diametaphyseal tibia fracture including union time and complicatios and compare
      wih other available management options in literature. METHODS: Twenty patients
      with closed distal diametaphyseal tibia fracture with or without intra articular
      extension (AO classification: 12 type 43A1, 4 type 43A2, 2 type 43A3 and 2 type
      43B1) treated with MIPO with LCP were prospectively followed for average duration
      of 18.45 months (range 5-30 months). RESULTS: Average duration of injury-hospital
      and injury-surgery interval was 12.8 hrs (range 2-44 hrs) and 4.45 days (range 1
      10 days) respectively. All fractures got united with an average duration of 18.5
      weeks (range14-28weeks) except one case of delayed union which was managed with
      percutaneous bone marrow injection. Two patients had union with valgus angulation
      less than 5 degees but no nonunion was found. There were two superficial and one
      deep post operative wound infection. All infections healed with extended period
      of intravenous antibiotics besides repeated debridemet for deep infection.
      Implants were removed in eight patients among whom six (30%) had malleolar skin
      irritation and pain due to prominent hardware. CONCLUSION: The present case
      series shows that MIPO with LCP is an effective treatment method in terms of
      union time and complications rate for distal diametaphyseal tibia fracture.
      Malleolar skin irritation is common problem because of prominent hardware.

PMID- 22610873
TI  - Bacterial conjunctivitis and of antibiotics in Dhulikhel Hospital-Kathmandu
      University Hospital.
AB  - BACKGROUND: Acute Infective Conjunctivitis may be due to viral or bacterial
      infection; though it is usually self limiting, topical antibiotics are often
      prescribed for rapid recovery. OBJECTIVES: This study aims to find out prevalence
      of bacterial infection among cases of acute infective conjunctivitis and to
      determine their in-vitro antibacterial susceptibilities to commonly used
      antibacterial agents and to find out whether the rampant use of topical
      antibiotics are at all necessary or justified. METHODS: A prospective analytical
      study conducted over a period of two years on clinically diagnosed cases of Acute
      Infective Conjunctivitis. Isolation and identification of microorganisms by
      culture and antimicrobial susceptibility test were done on conjunctival swabs
      from 65 patients. RESULTS: A total of 65 patients were included where children
      (one month to 10 years old) accounted for the commonest age group (35.4%).On Gram
      Stain, 90.8% were negative for pus cells or micro organisms. Gram positive cocci
      were found in 6.2% of cases. On culture, bacterial growth was seen in 11 cases
      (18.9%) among which Streptococcus pneumonia was seen in seven cases (10.8%).The
      analysis on in-vitro susceptibility testing showed that Chloramphenicol and
      Gentamicin were the most sensitive (78.6% of samples) drugs for conjunctivitis.
      CONCLUSION: Ophthalmic antibiotics should be prescribed judiciously in acute
      infective conjunctivitis even for suspected bacterial cases; since it is found to
      resolve spontaneously without any serious complications. Chloramphenicol and
      Gentamicin are drugs of choice if at all required.

PMID- 22610874
TI  - Fulminant hepatic failure due to dengue.
AB  - Dengue Fever (DF) is only rarely considered as a cause of acute liver failure
      even globally and only a few case reports of acute hepatic failure and
      encephalopathy occurring in DF in adults are available. We report a case of Acute
      Liver Failure due to Dengue during a major outbreak in 2010 in Chitwan. A 20 year
      old previously healthy female presented to the emergency department of Chitwan
      Medical College with fever, jaundice and altered sensorium. She was tested
      positive for Dengue IgM. Her biochemical and clinical parameters were suggestive
      of acute liver failure with total billirubin of 10.1 mg/dL, direct billirubin of
      5.2 mg/dL, ALT 5760 IU, AST 14100 IU, alkaline phosphatase of 1250 IU, PT INR of
      1.76 and platelet count of 30,000/mm3. Other causes for acute hepatic failure
      like acute viral hepatitis, leptospirosis, malaria, Reyes syndrome were ruled
      out. The patient was admitted and managed in the ICU with supportive care and
      platelet transfusion. With treatment she made a significant clinical and
      biochemical improvement with AST of 105 IU, ALT of 120 IU and platelet count of
      150,000/mm3. She was discharged after 11 days of hospital stay.

PMID- 22610875
TI  - Responses of biomarkers of a standardized (Cyprinus carpio) and a native
      (Pimelodella laticeps) fish species after in situ exposure in a periurban zone of
      Lujan river (Argentina).
AB  - The Lujan River basin, which is located in the northwest area of the province of
      Buenos Aires, Argentina, receives different anthropogenic inputs before reaching
      the Rio de la Plata estuary. The aim of this study was to assess the adverse
      impact of the river in the middle part of the basin. To this end, an in situ cage
      assay was conducted in two sites of the river (S1 and S2) near Lujan city, and
      the responses of hepatic biomarkers of both a standardized (Cyprinus carpio) and
      a native (Pimelodella laticeps) species were evaluated. The biomarkers studied
      were the condition factor and liver somatic indices (LSI), the enzymatic
      activities of catalase (CAT), superoxide dismutase (SOD), and glutathione-S
      transferase (GST), lipid peroxidation levels (thiobarbituric acid reactive
      substances, TBARS) and the induction of hepatic cytochrome P450 1A (CYP1A) and
      vitellogenin (Vtg) proteins. After 14 days, LSI and GST activity increased, and
      TBARS levels decreased in both species exposed at S1 and S2. In addition,
      exposure at both sites promoted an increase in SOD activity and CYP1A induction
      in C. carpio, while Vtg expression was observed only at S1. A shorter exposure
      period (7 days) caused an initial response only at S2 mediated only by CAT in P.
      laticeps. Finally, our results demonstrate that a 14-day period of in situ
      exposure in Lujan River could lead to antioxidant and biotransformation processes
      in C. carpio and to phase II biotransformation responses in P. laticeps.

PMID- 22610876
TI  - Ablative zone size created by radiofrequency ablation with and without
      chemoembolization in small hepatocellular carcinomas.
AB  - PURPOSE: We retrospectively evaluated whether combined use of chemoembolization
      expands ablative zone sizes created by radiofrequency (RF) ablation in patients
      with small hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: Fifty-seven
      patients treated with single RF ablation for solitary HCC measuring <=2 cm were
      assessed. RF ablation alone was done in nine patients and in 48 patients
      following chemoembolization, with an interval of 0 days in 6, 1-14 days in 27, 15
      28 days in 6, and >=4 weeks in 9. Ablative zone sizes, disappearance of tumor
      enhancement, and creation of sufficient ablative margins (>5 mm) were evaluated
      on contrast-enhanced computed tomography (CT) images. RESULTS: Both mean long
      axis (4.2-4.7 vs. 3.6 +/- 0.4 cm, p < 0.04) and short-axis (3.3-3.8 vs. 2.3 +/-
      0.5 cm, p < 0.03) diameters were expanded significantly when RF ablation was done
      until 4 weeks after chemoembolization than with RF ablation alone. Tumor
      enhancement disappeared in all patients. Frequency of achieving sufficient
      ablative margins was significantly higher when RF ablation was done until 4 weeks
      after chemoembolization than with RF ablation alone (74.0-83.3 vs. 22.2 %, p <
      0.05). CONCLUSION: Ablative zones created by RF ablation with chemoembolization
      become larger than RF ablation alone, leading to secure ablative margins.

PMID- 22610877
TI  - Built to bite: feeding kinematics, bite forces, and head shape of a specialized
      durophagous lizard, Dracaena guianensis (teiidae).
AB  - Most lizards feed on a variety of food items that may differ dramatically in
      their physical and behavioral characteristics. Several lizard families are known
      to feed upon hard-shelled prey (durophagy). Yet, specializations toward true
      molluscivory have been documented for only a few species. As snails are hard and
      brittle food items, it has been suggested that a specialized cranial morphology,
      high bite forces, and an adapted feeding strategy are important for such lizards.
      Here we compare head and skull morphology, bite forces, and feeding kinematics of
      a snail-crushing teiid lizard (Dracaena guianensis) with those in a closely
      related omnivorous species (Tupinambis merianae). Our data show that juvenile D.
      guianensis differ from T. merianae in having bigger heads and greater bite
      forces. Adults, however, do not differ in bite force. A comparison of feeding
      kinematics in adult Dracaena and Tupinambis revealed that Dracaena typically use
      more transport cycles, yet are more agile in manipulating snails. During
      transport, the tongue plays an important role in manipulating and expelling shell
      fragments before swallowing. Although Dracaena is slow, these animals are very
      effective in crushing and processing hard-shelled prey.

PMID- 22610878
TI  - Priority setting in health care: trends and models from Scandinavian experiences.
AB  - The Scandinavian welfare states have public health care systems which have
      universal coverage and traditionally low influence of private insurance and
      private provision. Due to raises in costs, elaborate public control of health
      care, and a significant technological development in health care, priority
      setting came on the public agenda comparatively early in the Scandinavian
      countries. The development of health care priority setting has been partly
      homogeneous and appears to follow certain phases. This can be of broader interest
      as it may shed light on alternative models and strategies in health care priority
      setting. Some general trends have been identified: from principles to procedures,
      from closed to open processes, and from experts to participation. Five general
      approaches have been recognized: The moral principles and values based approach,
      the moral principles and economic assessment approach, the procedural approach,
      the expert based practice defining approach, and the participatory practice
      defining approach. There are pros and cons with all of these approaches. For the
      time being the fifth approach appears attractive, but its lack of true
      participation and the lack of clear success criteria may pose significant
      challenges in the future.

PMID- 22610879
TI  - Housing with females increases testosterone and cortisol levels in captive groups
      of black-handed spider monkeys (Ateles geoffroyi).
AB  - The black-handed spider monkey (Ateles geoffroyi) is a seasonal reproducer that
      requires a seclusiveness to copulate and has a fusion-fission social system.
      These features impose important restrictions to achieve reproduction of captive
      animals. We investigated if group composition in captive spider monkeys has any
      endocrine effects. We compared testosterone and cortisol concentrations during
      the mating season in all-male and multifemale-multimale groups to study if the
      former condition impairs reproductive potential and increases stress.
      Concentrations of testosterone and cortisol of males living with females were
      higher than those of all-male groups. In the multifemale-multimale condition,
      dominant males had the highest levels of testosterone, while the youngest males
      showed the highest concentrations of cortisol. Results show that males adjust
      well to isosexual grouping, this being an appropriate condition to keep animals
      when controlled reproduction is sought.

PMID- 22610880
TI  - Rationalization of the behavior of M2(CH3CS2)4I (M = Ni, Pt) chains at room
      temperature from periodic density functional theory and ab initio cluster
      calculations.
AB  - The electrical conductivities and plausible charge-ordering states in the room
      temperature (r.t.) phase for MMX chains [Ni(2)(dta)(4)I](infinity) and
      [Pt(2)(dta)(4)I](infinity) (dta = CH(3)CS(2)(-)) have been analyzed with periodic
      density functional theory (DFT) and correlated ab initio calculations combined
      with the effective Hamiltonian theory. Periodic DFT calculations show a more
      delocalized nature of the ground state in [Pt(2)(dta)(4)I](infinity) compared to
      [Ni(2)(dta)(4)I](infinity), which features a rather large energy gap between the
      occupied and empty bands, and charge polarized dimer units. A larger electrical
      conductivity for the Pt chain can be expected, especially because the Fermi level
      lies within a band with contributions from Pt and I orbitals. Electronic
      structure parameters extracted from ab initio cluster calculations show that the
      large difference between the observed conductivities at 300 K for Ni and Pt
      compounds, of 3 orders of magnitude, cannot be explained from the parameters
      extracted from an embedded M(2)(dta)(4)I(2) dimer fragment alone. When tetramer
      fragments are considered, we observe that the interdimer transfer integral (t)
      between neighboring M(2) units connected by an iodine atom at correlated level is
      comparable in both chains. On the other hand, the energy to transfer an electron
      from a dimer to the neighboring one (Coulomb repulsion U) is three times larger
      in the Ni compound with respect to the Pt chain, in line with the poor
      conductivity of the former. The electronic structure of the M(4)(dta)(8)I(3)
      fragment points to an alternate charge-polarization state for Ni and an average
      valence state for Pt when the r.t. X-ray structure is considered.

PMID- 22610881
TI  - Basosquamous Cell Carcinoma of the Anus.

PMID- 22610882
TI  - IL-1 receptor antagonist blocks the lipopolysaccharide-induced inhibition of
      gastric motility in freely moving conscious rats.
AB  - BACKGROUND AND AIMS: Endotoxin/lipopolysaccharide (LPS) alters gastrointestinal
      functions. However, little is known as to whether LPS could change gastric antral
      contractility in freely moving conscious animals. We tried to clarify this
      problem and the associated mechanisms. METHODS: In this study, we recorded
      intraluminal gastric pressure waves in freely moving conscious rats by manometric
      catheter located in the antrum. Area under the manometric trace was evaluated as
      motor index (MI). RESULTS: Intraperitoneal injection of LPS at doses of 0.2 mg/kg
      or more significantly inhibited MI. The inhibition started immediately after the
      administration of LPS and lasted over 1 h. Intraperitoneal injection of IL-1beta
      potently decreased MI while neither IL-6 nor TNF-alpha inhibited gastric
      motility, suggesting IL-1beta specifically reduced gastric motility. Next, we
      examined the hypothesis that endogenous IL-1 mediates the LPS-induced inhibition
      of gastric motility. To address the speculation, an IL-1 receptor antagonist (IL
      1Ra) was used to block IL-1 signaling. Pretreatment with IL-1Ra at a dose of 20
      mg/kg significantly blocked the inhibition of gastric contractility by LPS at a
      dose of 0.2 mg/kg. CONCLUSIONS: These results suggest for the first time that LPS
      or IL-1beta is capable of inhibiting gastric motility in conscious rats and that
      endogenously released IL-1 may mediate the LPS-evoked inhibition of gastric
      antral motility. This evidence also led us to speculate that IL-1Ra may be a
      therapeutic tool for patients with disturbed gastrointestinal functions under
      septic conditions.

PMID- 22610883
TI  - Pancreaticoduodenectomy for the treatment of groove pancreatitis.
AB  - BACKGROUND AND AIM: Groove pancreatitis is a segmental form of chronic
      pancreatitis that can be treated with pancreaticoduodenectomy (PD), although
      outcome studies for this approach are lacking. We performed an assessment of pain
      symptoms, need for opioids, and weight gain following PD for symptomatic groove
      pancreatitis. METHODS: The study was a retrospective case series describing all
      patients with groove pancreatitis who underwent PD at our medical center. The
      primary outcome was the change in pain level and opioid use following PD.
      RESULTS: Five patients underwent PD for treatment of groove pancreatitis.
      Patients' perception of pain, using a 10-point visual analog scale, improved
      after surgery from 5.0 to 0.2. Opioid analgesics, as measured by oral morphine
      equivalents, dropped from 77.6 to 0 mg daily, with all five patients being
      completely free of opioids post-operatively. Weight loss ceased in all five
      patients, with an overall mean weight gain of 15.4 pounds post-operatively.
      CONCLUSIONS: PD reduces pain and opioid analgesic use in groove pancreatitis.
      This intervention should be considered for patients with this condition.

PMID- 22610885
TI  - Vitamin D binding protein gene polymorphisms and baseline vitamin D levels as
      predictors of antiviral response in chronic hepatitis C.
AB  - Vitamin D deficiency seems to predict the unsuccessful achievement of sustained
      viral response (SVR) after antiviral treatment in hepatitis C virus (HCV)
      difficult-to-treat genotypes. Vitamin D binding protein (GC) gene polymorphisms
      are known to influence vitamin D levels. This study was performed to assess
      whether the interaction between basal circulating vitamin D and the GC
      polymorphism plays a role in influencing the rate of antiviral responses in
      patients affected by chronic hepatitis C. In all, 206 HCV patients treated with a
      combination therapy of pegylated (PEG)-interferon plus ribavirin were
      retrospectively evaluated. GC rs7041 G>T, GC rs4588 C>A, and IL-28B rs12979860
      C>T polymorphisms were genotyped. Frequencies of GC rs7041 G>T and rs4588 C>A
      polymorphisms were: G/G = 64 (31.1%), G/T = 100 (48.5%), T/T = 42 (20.4%) and C/C
      = 108 (52.4%), C/A = 84 (40.8%), A/A = 14 (6.8%). Patients were divided into
      those carrying >=3 major alleles (wildtype [WT]+: G-C/G-C, G-C/T-C, G-C/G-A, N =
      100) and the remaining (WT-: G-C/T-A, T-A/T-C, T-A/T-A, T-C/T-C, N = 106). Four
      groups were identified: vitamin D <=20 ng/mL and WT-, vitamin D <=20 and WT+,
      vitamin D >20 and WT-, vitamin D >20 and WT+. In difficult-to-treat HCV genotypes
      the proportion of patients achieving SVR significantly increased with a linear
      trend from the first to the last group: 6/25 (24.0%), 9/24 (37.5%), 12/29
      (41.4%), 19/29 (65.5%) (P = 0.003). At multivariate analysis, having basal
      vitamin D >20 ng/mL plus the carriage of GC WT+ was found to be an independent
      predictor of SVR (odds ratio 4.52, P = 0.015). CONCLUSION: In difficult-to-treat
      HCV genotypes, simultaneous pretreatment normal serum vitamin D levels and the
      carriage of GC-globulin WT isoform strongly predicts the achievement of SVR after
      PEG-interferon plus ribavirin antiviral therapy.

PMID- 22610884
TI  - Feeding administration of Daikenchuto suppresses colitis induced by naive CD4+ T
      cell transfer into SCID mice.
AB  - BACKGROUND AND AIMS: Daikenchuto, a traditional Japanese herbal medicine,
      suppresses bacterial translocation by improvement of gastrointestinal motility
      and blood flow. As Daikenchuto reportedly reduces gastrointestinal inflammatory
      activity by these mechanisms, we analyzed whether Daikenchuto suppresses
      experimental colitis and reduces inflammatory cytokine expression in a mouse
      model. METHODS: Colitis was induced by transfer of naive CD4(+) T cells of BALB/c
      mice into SCID mice, and mice were given either control or 2.7 % Daikenchuto
      containing feed. We investigated body weight, clinical symptoms, histological
      changes, and Th1- and Th17-cytokine expression. Cytokine mRNA expression was
      analyzed using real-time RT-PCR. The ratio of IL-17(+) and IFN-gamma(+) CD4(+) T
      cells were analyzed by flow cytometry. RESULTS: Daikenchuto delayed the
      development of colitis and significantly reduced the histological inflammation
      scores. Analyses of cytokine mRNA revealed that Th17 cytokines were significantly
      decreased in colons of mice that received Daikenchuto. Absolute numbers of IL
      17(+) or IFN-gamma(+) CD4(+) T cells per colon were less in mice receiving
      Daikenchuto than in mice that received control feed, as both groups received
      naive CD4(+) T cells to induce colitis. CONCLUSIONS: We demonstrated that feeding
      administration of Daikenchuto suppresses colitis induced by naive CD4(+) T cell
      transfer into SCID mice. Daikenchuto may show clinical benefit in the treatment
      of human inflammatory bowel disease and further studies are warranted.

PMID- 22610886
TI  - Therapeutic live vaccines as a potential anticancer strategy.
AB  - The design of efficient cancer treatments is one of the major challenges of
      medical science. Therapeutic vaccines of cancer have been emerged as an
      attractive approach for their capacity of breaking the immune tolerance and
      invoking long-term immune response targeting cancer cells without autoimmunity.
      An efficient antigen delivery system is the key issue of developing an effective
      cancer vaccine. In this regard, live vaccination strategies including various
      live bacterial and viral vectors have attracted a great attention. Several
      bacterial strains such as Salmonella, Listeria monocytogenes and Lactococcus
      lactis effectively colonize solid tumors and act as antitumor therapeutics. On
      the other hand, the use of viruses as vaccine vectors such as Vaccinia,
      Adenovirus, Herpes simplex virus, Paramyxovirus and Retroviruses utilizes
      mechanisms that evolved in these microbes for entering cells and capturing the
      cellular machinery to express viral proteins. Viral/bacterial-vectored vaccines
      induce systemic T-cell responses including polyfunctional cytokine-secreting CD4+
      and CD8+ T-cells. However, there is an urgent need for the development of new
      safe live vaccine vectors that are capable of enhancing antigen presentation and
      eliciting potent immune responses without the risk of development of disease in
      humans. Recently, nonpathogenic parasites including Leishmania tarentolae,
      Toxoplasma gondii and Trypanosoma cruzi have emerged to be a novel candidate for
      gene delivery and heterologous genes expression. In this review, recent
      researches on cancer therapy using genetically modified bacteria and virus are
      summarized. In addition, live parasite-based vectors will be discussed as a novel
      anticancer therapeutic approach.

PMID- 22610889
TI  - Hsien Wu, the founder of Chinese biochemistry and nutriology.

PMID- 22610887
TI  - Two-dimensional gel electrophoresis in bacterial proteomics.
AB  - Two-dimensional gel electrophoresis (2-DE) is a gel-based technique widely used
      for analyzing the protein composition of biological samples. It is capable of
      resolving complex mixtures containing more than a thousand protein components
      into individual protein spots through the coupling of two orthogonal biophysical
      separation techniques: isoelectric focusing (first dimension) and polyacrylamide
      gel electrophoresis (second dimension). 2-DE is ideally suited for analyzing the
      entire expressed protein complement of a bacterial cell: its proteome. Its
      relative simplicity and good reproducibility have led to 2-DE being widely used
      for exploring proteomics within a wide range of environmental and medically
      relevant bacteria. Here we give a broad overview of the basic principles and
      historical development of gel-based proteomics, and how this powerful approach
      can be applied for studying bacterial biology and physiology. We highlight
      specific 2-DE applications that can be used to analyze when, where and how much
      proteins are expressed. The links between proteomics, genomics and mass
      spectrometry are discussed. We explore how proteomics involving tandem mass
      spectrometry can be used to analyze (post-translational) protein modifications or
      to identify proteins of unknown origin by de novo peptide sequencing. The use of
      proteome fractionation techniques and non-gel-based proteomic approaches are also
      discussed. We highlight how the analysis of proteins secreted by bacterial cells
      (secretomes or exoproteomes) can be used to study infection processes or the
      immune response. This review is aimed at non-specialists who wish to gain a
      concise, comprehensive and contemporary overview of the nature and applications
      of bacterial proteomics.

PMID- 22610888
TI  - MiR-122 in hepatic function and liver diseases.
AB  - As the most abundant liver-specific microRNA, microRNA-122 (miR-122) is involved
      in various physiological processes in hepatic function as well as in liver
      pathology. There is now compelling evidence that miR-122, as a regulator of gene
      networks and pathways in hepatocytes, plays a central role in diverse aspects of
      hepatic function and in the progress of liver diseases. This liver-enriched
      transcription factors-regulated miRNA promotes differentiation of hepatocytes and
      regulates lipid metabolism. With regard to liver diseases, miR-122 was shown to
      stimulate hepatitis C virus (HCV) replication through a unique and unusual
      interaction with two binding sites in the 5'-UTR of HCV genome to mediate the
      stability of the viral RNA, whereas inhibit the expression and replication of
      hepatitis B virus (HBV) by a miR-122-cylin G1/p53-HBV enhancer regulatory
      pathway. In addition, miR-122 acts as a suppressor of cell proliferation and
      malignant transformation of hepatocytes with remarkable tumor inhibition
      activity. Notably, a clinical trial targeting miR-122 with the anti-miR-122
      oligonucleotides miravirsen, the first miRNA targeted drug, has been initiated
      for treatment of HCV infection. With further understanding of the comprehensive
      roles of miR-122 in hepatic functions and the mechanisms involved in miR-122 down
      regulation in chronic hepatitis or hepatocellular carcinoma, miR-122 appears to
      be a promising candidate for effective therapeutic approaches against tumor and
      infectious diseases.

PMID- 22610890
TI  - Evaluation of Jeffamine(r)-cored PAMAM dendrimers as an efficient in vitro gene
      delivery system.
AB  - In this study, we investigated gene delivery properties of Jeffamine-cored
      polyamidoamine (PAMAM) dendrimers (JCPDs). The effects of dendrimer
      concentration, generation, and core size on the gene delivery have been analyzed.
      The experimental results showed that the JCPD effectively delivered plasmid DNA
      inside the HeLa cells, and the transfection efficiency improved considerably as
      the number of generation increased. The cytotoxicity of JCPD in different
      concentration was tested for HeLa cell line. JCPD was complexed with a lacZ gene
      carrying plasmid and tested for transfection efficiency using quantitative beta
      galactosidase expression assay. Additionally, confocal microscopy results
      revealed that JCPD effectively delivered green fluorescent protein-expressing
      plasmid into HeLa cells and produced fluorescent signal with satisfactory
      efficiency. The highest transfection efficiency was obtained from JCPDs G4 and
      G5, which mixed with expression plasmid vectors at a 10/1 weight ratio. These
      results indicated that under optimized conditions, JCPD can be considered as an
      efficient transfection reagent and can be effectively used for gene delivery
      applications.

PMID- 22610891
TI  - Primate dental ecology: How teeth respond to the environment.
AB  - Teeth are central for the study of ecology, as teeth are at the direct interface
      between an organism and its environment. Recent years have witnessed a rapid
      growth in the use of teeth to understand a broad range of topics in living and
      fossil primate biology. This in part reflects new techniques for assessing ways
      in which teeth respond to, and interact with, an organism's environment. Long
      term studies of wild primate populations that integrate dental analyses have also
      provided a new context for understanding primate interactions with their
      environments. These new techniques and long-term field studies have allowed the
      development of a new perspective-dental ecology. We define dental ecology as the
      broad study of how teeth respond to, or interact with, the environment. This
      includes identifying patterns of dental pathology and tooth use-wear, as they
      reflect feeding ecology, behavior, and habitat variation, including areas
      impacted by anthropogenic disturbance, and how dental development can reflect
      environmental change and/or stress. The dental ecology approach, built on
      collaboration between dental experts and ecologists, holds the potential to
      provide an important theoretical and practical framework for inferring ecology
      and behavior of fossil forms, for assessing environmental change in living
      populations, and for understanding ways in which habitat impacts primate growth
      and development. This symposium issue brings together experts on dental
      morphology, growth and development, tooth wear and health, primate ecology, and
      paleontology, to explore the broad application of dental ecology to questions of
      how living and fossil primates interact with their environments.

PMID- 22610892
TI  - What is dental ecology?
AB  - Teeth have long been used as indicators of primate ecology. Early work focused on
      the links between dental morphology, diet, and behavior, with more recent years
      emphasizing dental wear, microstructure, development, and biogeochemistry, to
      understand primate ecology. Our study of Lemur catta at the Beza Mahafaly Special
      Reserve, Madagascar, has revealed an unusual pattern of severe tooth wear and
      frequent tooth loss, primarily the result of consuming a fallback food for which
      these primates are not dentally adapted. Interpreting these data was only
      possible by combining our areas of expertise (dental anatomy [FC] and primate
      ecology [MS]). By integrating theoretical, methodological, and applied aspects of
      both areas of research, we adopted the term "dental ecology"-defined as the broad
      study of how teeth respond to the environment. Specifically, we view dental
      ecology as an interpretive framework using teeth as a vehicle for understanding
      an organism's ecology, which builds upon earlier work, but creates a new
      synthesis of anatomy and ecology that is only possible with detailed knowledge of
      living primates. This framework includes (1) identifying patterns of dental
      pathology and tooth use-wear, within the context of feeding ecology, behavior,
      habitat variation, and anthropogenic change, (2) assessing ways in which dental
      development and biogeochemical signals can reflect habitat, environmental change
      and/or stress, and (3) how dental microstructure and macro-morphology are adapted
      to, and reflect feeding ecology. Here we define dental ecology, provide a short
      summary of the development of this perspective, and place our new work into this
      context.

PMID- 22610893
TI  - The role of tooth enamel mechanical properties in primate dietary adaptation.
AB  - Primate teeth adapt to the physical properties of foods in a variety of ways
      including changes in occlusal morphology, enamel thickness, and overall size. We
      conducted a comparative study of extant primates to examine whether their teeth
      also adapt to foods through variation in the mechanical properties of the enamel.
      Nanoindentation techniques were used to map profiles of elastic modulus and
      hardness across tooth sections from the enamel-dentin junction to the outer
      enamel surface in a broad sample of primates including apes, Old World monkeys,
      New World monkeys, and lemurs. The measured data profiles feature considerable
      overlap among species, indicating a high degree of commonality in mechanical
      properties. These results suggest that differences in the load-bearing capacity
      of primate molar teeth are more a function of morphology-particularly tooth size
      and enamel thickness-than of underlying mechanical properties.

PMID- 22610894
TI  - Nanoindentation of lemur enamel: an ecological investigation of mechanical
      property variations within and between sympatric species.
AB  - The common morphological metrics of size, shape, and enamel thickness of teeth
      are believed to reflect the functional requirements of a primate's diet. However,
      the mechanical and material properties of enamel also contribute to tooth
      function, yet are rarely studied. Substantial wear and tooth loss previously
      documented in Lemur catta at the Beza Mahafaly Special Reserve suggests that
      their dental morphology, structure, and possibly their enamel are not adapted for
      their current fallback food (the mechanically challenging tamarind fruit). In
      this study, we investigate the nanomechanical properties, mineralization, and
      microstructure of the enamel of three sympatric lemur species to provide insight
      into their dietary functional adaptations. Mechanical properties measured by
      nanoindentation were compared to measurements of mineral content, prism
      orientation, prism size, and enamel thickness using electron microscopy.
      Mechanical properties of all species were similar near the enamel dentin junction
      and variations correlated with changes in microstructure (e.g., prism size) and
      mineral content. Severe wear and microcracking within L. catta's enamel were
      associated with up to a 43% reduction in nanomechanical properties in regions of
      cracking versus intact enamel. The mechanical and material properties of L.
      catta's enamel are similar to those of sympatric folivores and suggest that they
      are not uniquely mechanically adapted to consume the physically challenging
      tamarind fruit. An understanding of the material and mechanical properties of
      enamel is required to fully elucidate the functional and ecological adaptations
      of primate teeth.

PMID- 22610895
TI  - Linear enamel hypoplasia as an indicator of physiological stress in great apes:
      reviewing the evidence in light of enamel growth variation.
AB  - Physiological stress, such as malnutrition or illness, can disrupt normal enamel
      growth, resulting in linear enamel hypoplasias (LEHs). Although ecological
      factors may contribute to LEH expression, other factors, such as surface abrasion
      and enamel growth variables, are also likely to be involved. Attention to these
      other factors is necessary before we can begin to understand what LEH might
      signify in terms of ecological sources of physiological stress in non-human
      primates. This study focuses on assessing the contribution of these other factors
      to variation in LEH expression within and across great ape taxa. Here, we present
      LEH data from unabraded crown regions in samples of seven great ape species. We
      analyze these data with respect to lateral enamel formation time and the angles
      that striae of Retzius make with the enamel surface, as these variables are
      expected to affect variation in LEH expression. We find that although the
      duration of enamel formation is associated with sex differences in LEH
      expression, it is not clearly related to taxonomic variation in LEH expression,
      and does not explain the low frequency of LEH in mountain gorillas found in this
      and a previous study. Our data on striae of Retzius angles suggest that these
      influence LEH expression along the tooth crown and may contribute to the
      consistently high frequencies of LEH seen in Pongo in this and previous studies.
      We suggest that future work aimed at understanding species variation in these
      angles is crucial to evaluating taxonomic patterns of LEH expression in great
      apes.

PMID- 22610896
TI  - Interpreting food processing through dietary mechanical properties: a Lemur catta
      case study.
AB  - Knowledge of dietary mechanical properties can be informative about physical
      consequences to consumers during ingestion and mastication. In this article, we
      examine how Tamarindus indica fruits can affect dental morphology in a population
      of ring-tailed lemurs (Lemur catta) at Beza Mahafaly special reserve in
      southwestern Madagascar. Ring-tailed lemurs in tamarind dominated gallery forests
      exhibit extreme wear and tooth loss on their postcanine dentition that has been
      related to processing T. indica fruits. We measured and compared mechanical
      properties of individual food parts in the diet of ring-tailed lemurs in
      different seasons in 1999-2000, 2008, and 2010. Fracture toughness, hardness, and
      modulus of foods were measured with a portable mechanical tester. The ripe fruits
      of T. indica are indeed the toughest and hardest foods ingested by the lemurs. In
      addition, they are among the largest foods consumed, require high numbers of
      ingestive bites to process, and are the most frequently eaten by volume. During
      controlled cutting tests of the ripe fruit shell, multiple runaway side cracks
      form alongside the cut. Similarly, the lemurs repeatedly bite the ripe shell
      during feeding and thereby introduce multiple cracks that eventually fragment the
      shell. Studies of enamel microstructure (e.g., Lucas et al.: BioEssays 30 (2008)
      374-385; Campbell et al., 2011) advance the idea that the thin enamel of ring
      tailed lemur teeth is susceptible to substantial micro-cracking that rapidly
      erodes the teeth. We conclude that micro-cracking from repeated loads, in
      combination with the mechanical and physical properties of the fruit, is
      primarily responsible for the observed dental damage.

PMID- 22610897
TI  - Dental topography indicates ecological contraction of lemur communities.
AB  - Understanding the paleoecology of extinct subfossil lemurs requires
      reconstruction of dietary preferences. Tooth morphology is strongly correlated
      with diet in living primates and is appropriate for inferring dietary ecology.
      Recently, dental topographic analysis has shown great promise in reconstructing
      diet from molar tooth form. Compared with traditionally used shearing metrics,
      dental topography is better suited for the extraordinary diversity of tooth form
      among subfossil lemurs and has been shown to be less sensitive to phylogenetic
      sources of shape variation. Specifically, we computed orientation patch counts
      rotated (OPCR) and Dirichlet normal energy (DNE) of molar teeth belonging to 14
      species of subfossil lemurs and compared these values to those of an extant lemur
      sample. The two metrics succeeded in separating species in a manner that provides
      insights into both food processing and diet. We used them to examine the changes
      in lemur community ecology in Southern and Southwestern Madagascar that
      accompanied the extinction of giant lemurs. We show that the poverty of
      Madagascar's frugivore community is a long-standing phenomenon and that
      extinction of large-bodied lemurs in the South and Southwest resulted not merely
      in a loss of guild elements but also, most likely, in changes in the ecology of
      extant lemurs.

PMID- 22610898
TI  - Lemur habitat and dental senescence in Ranomafana National Park, Madagascar.
AB  - Not only can teeth provide clues about diet, but they also can be indicators of
      habitat quality. Conspecific groups living in different habitats with different
      kinds of foods may exhibit different rates of dental attrition because their
      teeth are less well adapted to some foods than to others. Ecological
      disequilibrium describes the situation in which animals live in habitats to which
      they are relatively poorly adapted. We test whether dental senescence, the wear
      related decrease in dental functionality that is associated with decreased
      survival of infants born to older Propithecus edwardsi females, can be explained
      by ecological disequilibrium. Specifically, we compare the rates of dental wear
      in sifaka groups living in nearby habitats that differ in the degree of
      anthropogenically induced disturbance. We hypothesize that sifakas living in
      disturbed areas have an unusual rate of tooth wear compared to those living in a
      more pristine area, and that dental senescence is a consequence of an atypically
      high wear rate in a degraded habitat. To test whether habitat quality affects
      tooth wear more generally, we compare rates of use-wear in two subsets of
      Microcebus rufus living in either relatively undisturbed or disturbed habitats.
      Contrary to our predictions, we did not detect different rates of tooth wear in
      disturbed versus undisturbed habitats for either species and consider that
      reproductively detrimental dental senescence in P. edwardsi females is unlikely
      to be a pathological consequence of ecological disequilibrium.

PMID- 22610899
TI  - The impact of dental impairment on ring-tailed lemur food processing performance.
AB  - During mastication, foods are reduced into particles suitable for swallowing and
      digestion. Smaller particles possess a greater surface area per unit of volume on
      which digestive enzymes and bacteria may work than relatively larger particles,
      and are thus more readily digested. As dental morphology facilitates the
      breakdown of diets with specific mechanical properties, extensive dental wear
      and/or tooth loss may impede an individual's ability to break down and exploit
      foods. We present data demonstrating a relationship between dental impairment and
      particle size in 43 fecal samples from 33 ring-tailed lemurs at the Beza Mahafaly
      Special Reserve (BMSR), Madagascar. All fecal samples were sifted through three
      sieves of decreasing size (11.2 mm, 4.75 mm, and 1.0 mm). The resulting fraction
      in each sieve was then weighed and assessed in relation to individual dental
      impairment status. With increasing wear, the percentage of each sample within the
      1.0 mm sieve decreases, whereas that in the 11.2 mm sieve increases with
      increasing postcanine wear, although these effects are not present when limited
      to individuals without tooth loss. Individuals with tooth loss also demonstrate
      larger proportions of fecal material 1.0-4.75 mm in size. Dental impairment
      results in larger food particles and potentially less efficient utilization of
      foods. When fecal material was examined by leaf vs. fruit content, individuals
      with tooth loss demonstrated reduced proportions of fruit in the 1.0 mm and 11.2
      mm sieves. These data suggest individuals with tooth loss consume less fruit than
      those without loss, potentially reflecting a reduced ability to process tamarind
      fruit, a key fallback resource at BMSR.

PMID- 22610900
TI  - Platyrrhine incisors and diet.
AB  - Despite the relatively large size of anthropoid incisors in relation to the
      remainder of the dental arcade, and their prominent role in the preprocessing of
      food prior to ingestion, comparatively little is known about the functional
      morphology of anthropoid incisor shape and crown curvature. The relationship
      between incisor allometry and diet is well documented for both platyrrhines and
      catarrhines; however, similar relationships between incisor shape and crown
      curvature have to date only been reported for living and fossil members of the
      superfamily Hominoidea. Given the limited taxonomic diversity among the extant
      members of that group, it is difficult to firmly establish the relative influence
      of phylogeny and dietary function in the governance of incisor crown curvature.
      Unlike hominoids, which are represented by only five living genera, extant
      platyrrhines are a more varied group that includes 16 ecologically diverse
      genera. In an effort to clarify the functional relationship between maxillary and
      mandibular incisor crown curvature and diet, this study uses high resolution
      polynomial curve fitting to quantify mesiodistal and cervicoincisal curvature for
      a taxonomically diverse platyrrhine sample (n = 133 individuals representing 18
      taxa) with well documented dietary behavior. Results were consistent with prior
      analyses of hominoid incisor curvature and identify a significant and positive
      correlation between incisor crown curvature and diet such that increasing
      curvature is associated with a proportionate increase in frugivory. These results
      are independent confirmation of the results reported from a previous analysis of
      hominoid incisor curvature and provide new evidence to suggest that diet is the
      primary governing factor influencing anthropoid incisor curvature.

PMID- 22610901
TI  - Relationships between the diet and dentition of Asian leaf monkeys.
AB  - Colobines have been generally described as primates that use the anterior teeth
      minimally, but the posterior teeth extensively, to process leaves and related
      food items. However, variation among leaf monkeys in both anterior and posterior
      dental morphology has been recognized for decades. In this study, we turn to
      Hylander's (Science 189 (1975) 1095-1098) analysis of anterior incisor row length
      and Kay's (Adaptations for foraging in nonhuman primates, 1984) examination of
      relative molar crest length to test hypotheses proposed by them for Asian
      colobines. We present findings based on data from the largest Asian colobine
      sample measured to date. Our findings for incisor row length and molar cresting
      are not amenable to broad generalizations. In those instances when our
      morphological findings concur with those of Hylander (Science 189 (1975) 1095
      1098) and Kay and Hylander (The ecology of arboreal folivores, 1978), the
      ecological evidence seldom supports the morphological predictions. The
      disassociation between diet and dental patterns may be a consequence of
      differential selection by fallback foods, anthropogenic disturbance or climatic
      shifts limiting preferred diets, or the use of food types as opposed to food
      mechanical properties for dietary categorization. We also found that in the case
      of both incisor row length and molar crest length, the patterns for males and
      females differed markedly. The reasons for these differences may in part be
      ascribed to the metabolic challenges faced by females and subsequent niche
      partitioning. We propose integrated analyses of the ingestive and digestive
      systems of our study taxa to clarify relationships among behavior, dental
      morphology, and diet in extant and extinct colobines.

PMID- 22610902
TI  - A dental topographic analysis of chimpanzees.
AB  - Molar tooth morphology is generally said to reflect a compromise between
      phylogenetic and functional influences. Chimpanzee subspecies have been reported
      to exhibit differences in molar dimensions and nonmetric traits, but these have
      not been related to differences in their diets. And in fact, observations to date
      of the diets of chimpanzees have not revealed consistent differences among
      subspecies. This study uses dental topographic analyses shown to reflect diet
      related differences in occlusal morphology among primate species, to assess
      within-species variation among chimpanzee subspecies. High-resolution casts from
      museum collections were examined by laser scanning, and resulting data were
      analyzed using GIS algorithms and a two-factor ANOVA model. Although differences
      were noted between wear stages within subspecies in surface slope, relief, and
      angularity, none were found to distinguish the subspecies from one another in
      these attributes. This might reflect limitations in the ability of this method to
      detect diet-related differences, but is also consistent with a lack of
      differences in functionally relevant aspects of occlusal morphology among
      chimpanzee subspecies.

PMID- 22610903
TI  - Dental microwear and stable isotopes inform the paleoecology of extinct hominins.
AB  - Determining the diet of an extinct species is paramount in any attempt to
      reconstruct its paleoecology. Because the distribution and mechanical properties
      of food items may impact postcranial, cranial, mandibular, and dental
      morphologies related to their procurement, ingestion, and mastication, these
      anatomical attributes have been studied intensively. However, while mechanical
      environments influence skeletal and dental features, it is not clear to what
      extent they dictate particular morphologies. Although biomechanical explanations
      have been widely applied to extinct hominins in attempts to retrodict dietary
      proclivities, morphology may say as much about what they were capable of eating,
      and perhaps more about phylogenetic history, than about the nature of the diet.
      Anatomical attributes may establish boundary limits, but direct evidence left by
      the foods that were actually (rather than hypothetically) consumed is required to
      reconstruct diet. Dental microwear and the stable light isotope chemistry of
      tooth enamel provide such evidence, and are especially powerful when used in
      tandem. We review the foundations for microwear and biogeochemistry in diet
      reconstruction, and discuss this evidence for six early hominin species
      (Ardipithecus ramidus, Australopithecus anamensis, Au. afarensis, Au. africanus,
      Paranthropus robustus, and P. boisei). The dietary signals derived from microwear
      and isotope chemistry are sometimes at odds with inferences from biomechanical
      approaches, a potentially disquieting conundrum that is particularly evident for
      several species.

PMID- 22610904
TI  - Human DNA damage by the synergistic action of 4-aminobiphenyl and nitric oxide:
      an immunochemical study.
AB  - 4-Aminobiphenyl (4-ABP), an aromatic amine is a major environmental carcinogen
      found mainly in cigarette smoke. It has been vastly implicated in mutagenesis and
      cancer development. In this study, commercially available human placental DNA was
      exposed to 4-ABP (1.3 mM) in presence of sodium nitroprusside (SNP; 8 mM) at 37
      degrees C for 3 h. The 4-ABP + SNP-mediated structural changes in human DNA were
      studied by ultraviolet, circular dichroism and fluorescence spectroscopy, thermal
      melting profile, agarose gel electrophoresis, and nuclease S1 digestibility
      assay. Spectroscopical analysis and melting temperature studies suggest
      structural perturbations in the DNA as a result of modification. This might be
      due to generation of single-stranded regions and destabilization of hydrogen
      bonds. Modification was also visualized in agarose gel electrophoresis.
      Furthermore, nuclease S1 digestibility confirmed the generation of single strand
      breaks. Rabbits challenged with 4-ABP-SNP-modified human DNA-induced high-titer
      immunogen-specific antibodies, which showed Cross-reaction with
      modified/unmodified DNA bases and ss-DNA in competitive inhibition assay. The
      immunogen specificity of induced antibodies against 4-ABP-SNP-modified human DNA
      was further confirmed in gel retardation assay. It may be concluded that
      induction of anti-modified DNA antibodies could be due to perturbation in the DNA
      structure and its subsequent recognition by immunoregulatory cells as a foreign
      molecule.

PMID- 22610905
TI  - The interaction between beta1 integrins and ERK1/2 in osteogenic differentiation
      of human mesenchymal stem cells under fluid shear stress modelled by a perfusion
      system.
AB  - Fluid shear stress (FSS) is an important biomechanical factor regulating the
      osteogenic differentiation of human mesenchymal stem cells (hMSCs) and is
      therefore widely used in bone tissue engineering. However, the
      mechanotransduction of FSS in hMSCs remains largely unknown. As beta1 integrins
      are considered to be important mechanoreceptors in other cells, we suspect that
      beta1 integrins should also be important for hMSCs to sense the stimulation of
      FSS. We used a perfusion culture system to produce FSS loading on hMSCs seeded in
      PLGA three-dimensional (3D) scaffolds and investigated the roles of beta1
      integrins, FAK and ERK1/2 in FSS-induced osteogenic differentiation of hMSCs. Our
      results showed that FSS not only markedly increased ALP activity and the
      expression of ALP, OCN, Runx2 and COLIalpha genes but also significantly enhanced
      the phosphorylation of ERK1/2, Runx2 and FAK. FSS-induced activation of ERK1/2
      and FAK was inhibited by blockade of the connection between beta1 integrins and
      ECM with RGDS peptide and integrins beta1 monoclonal antibody. Our study also
      found that FSS could upregulate the expression level of beta1 integrins and that
      this upregulation could be abolished by PD98059. Further investigation indicated
      that FSS-activated ERK1/2 led to the phosphorylation of IkappaBalpha and NFkappaB
      p65. The activation of NFkappaB p65 resulted in the upregulation of beta1
      integrin expression. Therefore, it could be inferred that beta1 integrins should
      sense the stimulation of FSS and thus activate ERK1/2 through activating of FAK,
      and FSS-activated ERK1/2 feedback to upregulate the expression of beta1 integrins
      through activating NFkappaB.

PMID- 22610906
TI  - Incidence of dsRNA mycoviruses in a collection of Aspergillus fumigatus isolates.
AB  - A collection of clinical and environmental isolates of the opportunistic human
      pathogen, Aspergillus fumigatus, were screened for the presence of mycoviruses
      and 6.6 % of 366 isolates contained dsRNA segments ranging in size from ~1.0 to
      4.0 kbp. The dsRNAs were categorised into three different groups comprising
      bipartite dsRNAs, quadripartite dsRNAs, representative isolates of which have
      both been sequenced, and an uncharacterised mycovirus, whose genome apparently
      consists of four dsRNAs 1-2.5 kbp in size. Here, we describe dsRNA incidence in
      the A. fumigatus isolates examined, their provenance and also note that on
      occasion individual isolates were infected with two groups of different dsRNAs.

PMID- 22610907
TI  - Effect of exercise on blood pressure in type 2 diabetes: a randomized controlled
      trial.
AB  - BACKGROUND: Increased blood pressure (BP) in type 2 diabetes (T2DM) markedly
      increases cardiovascular disease morbidity and mortality risk compared to having
      increased BP alone. OBJECTIVE: To investigate whether exercise reduces suboptimal
      levels of untreated suboptimal BP or treated hypertension. DESIGN: Prospective,
      randomized controlled trial for 6 months. SETTING: Single center in Baltimore,
      MD, USA. PATIENTS: 140 participants with T2DM not requiring insulin and untreated
      SBP of 120-159 or DBP of 85-99 mmHg, or, if being treated for hypertension, any
      SBP <159 mmHg or DBP<99 mmHg; 114 completed the study. INTERVENTION: Supervised
      exercise, 3 times per week for 6 months compared with general advice about
      physical activity. MEASUREMENTS: Resting SBP and DBP (primary outcome); diabetes
      status, arterial stiffness assessed as carotid-femoral pulse-wave velocity (PWV),
      body composition and fitness (secondary outcomes). RESULTS: Overall baseline BP
      was 126.8 +/- 13.5 / 71.7 +/- 9.0 mmHg, with no group differences. At 6 months,
      BP was unchanged from baseline in either group, BP 125.8 +/- 13.2 / 70.7 +/- 8.8
      mmHg in controls; and 126.0 +/- 14.2 / 70.3 +/- 9.0 mmHg in exercisers, despite
      attaining a training effects as evidenced by increased aerobic and strength
      fitness and lean mass and reduced fat mass (all p<0.05), Overall baseline PWV was
      959.9 +/- 333.1 cm/s, with no group difference. At 6-months, PWV did not change
      and was not different between group; exercisers, 923.7 +/- 319.8 cm/s, 905.5 +/-
      344.7, controls. LIMITATIONS: A completion rate of 81 %. CONCLUSIONS: Though
      exercisers improve fitness and body composition, there were no reductions in BP.
      The lack of change in arterial stiffness suggests a resistance to exercise
      induced BP reduction in persons with T2DM.

PMID- 22610909
TI  - Cognitive errors and logistical breakdowns contributing to missed and delayed
      diagnoses of breast and colorectal cancers: a process analysis of closed
      malpractice claims.
AB  - PURPOSE: To erform a process analysis of missed and delayed diagnoses of breast
      and colorectal cancers to identify: (1) the cognitive and logistical factors that
      lead to these diagnostic errors, and (2) prevention strategies. METHODS: Using 56
      cases (43 breast, 13 colon) of missed and delayed diagnosis, we performed
      structured analyses to identify specific points in the diagnostic process in
      which errors occurred. Each error was classified as either a cognitive error or
      logistical breakdown. Finally, two physician-investigators identified strategies
      to prevent the errors in each case. RESULTS: Virtually all cases involved one or
      more cognitive errors (53/56, 95 %) and approximately half (31/56, 55 %) involved
      logistical breakdowns. The clinical activity most prone to cognitive error was
      the selection of the diagnostic strategy, both during the office visit (25/56, 45
      %) and during interpretation of test results (22/50, 44 %). Arrangement of follow
      up visits with a primary care physician (8/29, 28 %) or specialist physician
      (7/29, 26 %) were especially prone to logistical breakdowns. Adherence to current
      clinical guidelines could have prevented at least one error in 66 % of cases and
      assistance from a patient advocate could have prevented at least one error in 48
      % of cases. CONCLUSIONS: Cognitive errors and logistical breakdowns are common
      among missed and delayed diagnoses of breast and colorectal cancers. Prevention
      strategies should focus on ensuring improving the effectiveness and use of
      clinical guidelines in the selection of diagnostic strategy, both during office
      visits and when interpreting test results. Tools to facilitate communication and
      to ensure that follow-up visits occur should also be considered.

PMID- 22610910
TI  - Missed opportunities for advance care planning.

PMID- 22610911
TI  - Ferulate protects the epithelial barrier by maintaining tight junction protein
      expression and preventing apoptosis in tert-butyl hydroperoxide-induced Caco-2
      cells.
AB  - Epithelial barrier function is determined by both transcellular and paracellular
      permeability, the latter of which is mainly influenced by tight junctions (TJs)
      and apoptotic leaks within the epithelium. We investigated the protective effects
      of ferulate on epithelial barrier integrity by examining permeability, TJ protein
      expression, and apoptosis in Caco-2 cells treated with tert-butyl hydroperoxide
      (t-BHP), a strong reactive species inducer. Caco-2 cells pretreated with ferulate
      (5 or 15 MUM) were exposed to t-BHP (100 MUM), and ferulate suppressed the t-BHP
      mediated increases in reactive species and epithelial permeability in Caco-2
      cells. Moreover, ferulate inhibited epithelial cell leakage induced by t-BHP,
      which was accompanied by decreased expression of the TJ proteins zonula occludens
      1 and occludin. In addition, pretreatment with ferulate markedly protected cells
      against t-BHP-induced apoptosis, as evidenced by decreased nuclear condensation,
      cytochrome c release, and caspase-3 cleavage and an increased Bax/Bcl-2 ratio.
      These results suggest that ferulate protects the epithelial barrier of Caco-2
      cells against oxidative stress, which results in increased epithelial
      permeability, decreased TJ protein expression, and increased apoptosis. The most
      significant finding of our study is the demonstration of protective, ferulate
      mediated antioxidant effects on barrier integrity, with a particular focus on
      intracellular molecular mechanisms.

PMID- 22610913
TI  - Life-history patterns of Cuban poeciliid fishes (Teleostei: Cyprinodontiformes).
AB  - The following work provides basic information about the life history of 10 Cuban
      species of the family Poeciliidae. Adult fish stocks were captured in their
      natural habitat, and litters obtained from them were raised and maintained in
      captivity for 19 weeks. For each species, we present the mean value of newborn
      length (TLo ), age at sexual maturity (AM), total length at sexual maturity
      (TLM), as well as the patterns of postnatal growth in aquarium conditions, which
      were described using size-age curves and nonlinear regression equations (Richards
      model). There are differences in growth dynamics among species. In general,
      growth rates differ for both sexes in all poeciliids studied, males maturing
      earlier than females, who reach higher values of total length at the 19th week
      (TLf ). Sexual size dimorphism could be explained by the specific roles of each
      sex (fecundity in females and early maturity in males) while differences in
      growth among species could be related to their distribution patterns in the wild.
      The data summarized in this contribution can be useful for the conservation of
      these fish species.

PMID- 22610912
TI  - Is PACAP the major neurotransmitter for stress transduction at the
      adrenomedullary synapse?
AB  - It has been known for more than a decade that the neuropeptide PACAP (pituitary
      adenylate cyclase-activating polypeptide) is co-stored with acetylcholine in the
      splanchnic nerve terminals innervating the adrenal medulla. Both transmitters are
      robust secretagogues for catecholamine release from chromaffin cells. Here, we
      review the unique contribution of PACAP to the functioning of the splanchnic
      adrenal synapse in stress. While acetylcholine is released across a wide range of
      firing frequencies, PACAP is released only at high frequencies of stimulation,
      and its role in the regulation of epinephrine secretion and biosynthesis is
      highly specialized. PACAP is responsible for long-term catecholamine secretion
      using secretory mechanisms different from the rapidly desensitizing
      depolarization evoked by acetylcholine through nicotinic receptor activation.
      PACAP signaling also maintains catecholamine synthesis required for sustained
      secretion during prolonged stress via induction of the enzymes TH and PNMT, and
      enhances transcription of additional secreted molecules found in chromaffin cells
      that alter further secretion through both autocrine and paracrine mechanisms.
      PACAP thus mediates chromaffin cell plasticity via functional encoding of
      cellular experience. These features of PACAP action at the splanchnic-adrenal
      synapse may be paradigmatic for the general actions of neuropeptides as effectors
      of stimulus-secretion-synthesis coupling in stress.

PMID- 22610914
TI  - Computational investigations on covalent dimerization/oligomerization of
      polyacenes: is it relevant to soot formation?
AB  - We have postulated a novel pathway that could assist in the nucleation of soot
      particles through covalent dimerization and oligomerizations of a variety of
      PAHs. DFT calculations were performed with the objective of obtaining the
      relative thermal stabilities and formation probabilities of oligomeric species
      that exploit the facile dimerization that is known to occur in linear
      oligoacenes. We propose that the presence of small stretches of linear
      oligoacence (tetracene or longer) in extended PAH, either embedded or tethered,
      would be adequate for enabling the formation of such dimeric and oligomeric
      adducts; these could then serve as nuclei for the growth of soot particles. Our
      studies also reveal the importance of pi-stacking interactions between extended
      aromatic frameworks in governing the relative stabilities of the oligomeric
      species that are formed.

PMID- 22610915
TI  - Hepatitis C virus-induced up-regulation of microRNA-155 promotes
      hepatocarcinogenesis by activating Wnt signaling.
AB  - Hepatitis C virus (HCV) infection usually induces chronic hepatic inflammation,
      which favors the initiation and progression of hepatocellular carcinoma (HCC).
      Moreover, microRNA-155 (miR-155) plays an important role in regulating both
      inflammation and tumorigenesis. However, little is known about whether and how
      miR-155 provides the link between inflammation and cancer. In this study we found
      that miR-155 levels were markedly increased in patients infected with HCV. MiR
      155 transcription was regulated by nuclear factor kappa B (NF-kappaB), and p300
      increased NF-kappaB-dependent miR-155 expression. The overexpression of miR-155
      significantly inhibited hepatocyte apoptosis and promoted cell proliferation,
      whereas miR-155 inhibition induced G(0) /G(1) arrest. Up-regulated miR-155
      resulted in nuclear accumulation of beta-catenin and a concomitant increase in
      cyclin D1, c-myc, and survivin. Gain-of-function and loss-of-function studies
      demonstrated that miR-155 promoted hepatocyte proliferation and tumorigenesis by
      increasing Wnt signaling in vitro and in vivo, and DKK1 (Wnt pathway inhibitor)
      overexpression inhibited the biological role of miR-155 in hepatocytes. Finally,
      adenomatous polyposis coli (APC), which negatively regulates Wnt signaling, was
      identified as the direct and functional target of miR-155. CONCLUSION: HCV
      induced miR-155 expression promotes hepatocyte proliferation and tumorigenesis by
      activating Wnt signaling. The present study provides a better understanding of
      the relationship between inflammation and tumorigenesis, and thus may be helpful
      in the development of effective diagnosis and treatment strategies against HCV
      HCC.

PMID- 22610916
TI  - The role of angiotensin receptor blockers in reducing the risk of cardiovascular
      disease.
AB  - New approaches to the definition and treatment of hypertension have increased
      emphasis on reducing overall cardiovascular risk and on targeting the underlying
      mechanisms of cardiovascular disease. During the past several decades, renin
      angiotensin-aldosterone system (RAAS) activation has emerged as an important
      factor in the pathophysiology of endothelial dysfunction and cardiovascular
      disease (CVD). Angiotensin-converting enzyme inhibitors (ACEIs) have well
      established efficacy for treating CVD, but their use may be limited by
      intolerable side effects, such as cough and angioedema. Angiotensin II receptor
      blockers (ARBs), a different class of RAAS inhibitors, are considered a viable
      alternative to ACEIs. Clinical trials have further elucidated the role of ARBs in
      CVD. This article reviews the mechanism of action of ARBs and selected clinical
      trials of ARBs in CVD.

PMID- 22610919
TI  - Crystal structure of the ubiquitin-like domain of human TBK1.
AB  - TANK-binding kinase 1 (TBK1) is an important enzyme in the regulation of cellular
      antiviral effects. TBK1 regulates the activity of the interferon regulatory
      factors IRF3 and IRF7, thereby playing a key role in type I interferon (IFN)
      signaling pathways. The structure of TBK1 consists of an N-terminal kinase
      domain, a middle ubiquitin-like domain (ULD), and a C-terminal elongated helical
      domain. It has been reported that the ULD of TBK1 regulates kinase activity,
      playing an important role in signaling and mediating interactions with other
      molecules in the IFN pathway. In this study, we present the crystal structure of
      the ULD of human TBK1 and identify several conserved residues by multiple
      sequence alignment. We found that a hydrophobic patch in TBK1, containing
      residues Leu316, Ile353, and Val382, corresponding to the "Ile44 hydrophobic
      patch" observed in ubiquitin, was conserved in TBK1, IkappaB kinase epsilon
      (IKKE/IKKi), IkappaB kinase alpha (IKKalpha), and IkappaB kinase beta (IKKbeta).
      In comparison with the structure of the IKKbeta ULD domain of Xenopus laevis, we
      speculate that the Ile44 hydrophobic patch of TBK1 is present in an
      intramolecular binding surface between ULD and the C-terminal elongated helices.
      The varying surface charge distributions in the ULD domains of IKK and IKK
      related kinases may be relevant to their specificity for specific partners.

PMID- 22610921
TI  - Identification of putative candidate genes involved in cuticle formation in
      Prunus avium (sweet cherry) fruit.
AB  - BACKGROUND AND AIMS: The cuticular membrane (CM) of Prunus avium (sweet cherry)
      and other fleshy fruit is under stress. Previous research indicates that the
      resultant strain promotes microscopic cuticular cracking. Microcracks impair the
      function of the CM as a barrier against pathogens and uncontrolled water
      loss/uptake. Stress and strain result from a cessation of CM deposition during
      early development, while the fruit surface continues to expand. The cessation of
      CM deposition, in turn, may be related to an early downregulation of CM-related
      genes. The aims of this study were to identify genes potentially involved in CM
      formation in sweet cherry fruit and to quantify their expression levels. METHODS:
      Fruit growth and CM deposition were quantified weekly from anthesis to maturity
      and rates of CM deposition were calculated. Sequences of genes expressed in the
      sweet cherry fruit skin (exocarp) were generated using high-throughput sequencing
      of cDNA and de novo assembly and analysed using bioinformatics tools. Relative
      mRNA levels of selected genes were quantified in the exocarp and fruit flesh
      (mesocarp) weekly using reverse transcriptase-quantitative real-time PCR and
      compared with the calculated CM deposition rate over time. KEY RESULTS: The rate
      of CM deposition peaked at 93 (+/-5) MUg per fruit d(-1) about 19 d after
      anthesis. Based on sequence analyses, 18 genes were selected as potentially
      involved in CM formation. Selected sweet cherry genes shared up to 100 and 98 %
      similarity with the respective Prunus persica (peach) and Arabidopsis thaliana
      genes. Expression of 13 putative CM-related genes was restricted to the exocarp
      and correlated positively with the CM deposition rate. CONCLUSIONS: The results
      support the view that the cessation of CM deposition during early sweet cherry
      fruit development is accounted for by a downregulation of genes involved in CM
      deposition. Genes that merit further investigation include PaWINA, PaWINB,
      PaLipase, PaLTPG1, PaATT1, PaLCR, PaGPAT4/8, PaLACS2, PaLACS1 and PaCER1.

PMID- 22610920
TI  - The brain-derived neurotrophic-factor (BDNF) val66met polymorphism is associated
      with geriatric depression: a meta-analysis.
AB  - Depression has been associated with reduced expression of brain-derived
      neurotrophic factor (BDNF) in the hippocampus. Genetic association studies of the
      BDNF Val66Met polymorphism (rs6265) in geriatric depression have produced
      inconsistent results. A meta-analysis of studies was conducted to compare the
      frequency of the BDNF Val66Met variant between cases with geriatric depression
      and age-matched controls. A total of five studies involving 523 cases with
      geriatric depression and 1,220 psychiatrically healthy controls was included. Met
      allele carriers had an increased risk for geriatric depression when compared to
      Val/Val homozygotes (P = 0.004, OR = 1.48, 95% CI = 1.13-1.93). Our findings
      suggest the BDNF Met allele may confer increased risk for depression as
      individual age.

PMID- 22610922
TI  - Fidaxomicin failures in recurrent Clostridium difficile infection: a problem of
      timing.

PMID- 22610923
TI  - Antiretroviral medication errors remain high but are quickly corrected among
      hospitalized HIV-infected adults.
AB  - BACKGROUND: Antiretroviral therapy (ART) medication errors can lead to drug
      resistance, treatment failure, and death. Prior research suggests that ART
      medication errors are on the rise in US hospitals. This analysis provides a
      current estimate of inpatient antiretroviral prescribing errors. METHODS:
      Retrospective review of medication orders during the first 48 hours of
      hospitalization for patients with human immunodeficiency virus (HIV) infection
      admitted to the Johns Hopkins Hospital between 1 January and 31 December 2009.
      Errors were classified as (1) incomplete regimen, (2) incorrect dosage, (3)
      incorrect schedule, and (4) nonrecommended drug-drug combinations. Multivariable
      regression was used to identify factors associated with errors. RESULTS: A total
      of 702 admissions occurred in 2009. Of these, 380 had ART medications prescribed
      on the first day and 308 on the second day of hospitalization. A total of 145 ART
      medication errors in 110 admissions were identified on the first day (29%), and
      22 errors were identified in 21 admissions on the second day (7%). The most
      common errors were incomplete regimen and incorrect dosage or schedule. Protease
      inhibitors accounted for the majority of dosing and scheduling errors (71%-73%).
      Compared with patients admitted to the HIV/AIDS service, those admitted to
      surgical services were at increased risk of errors (adjusted odds ratio, 3.10;
      95% confidence interval, 1.18-8.18). CONCLUSIONS: ART medication errors are
      common among hospitalized HIV-infected patients on the first day of admission,
      but most are corrected within 48 hours. Interventions are needed to safeguard
      patients and prevent serious complications of ART medication errors especially
      during the first 24 hours of hospitalization.

PMID- 22610924
TI  - Editorial commentary: Antifungal therapeutic drug monitoring progress: getting it
      right the first time.

PMID- 22610925
TI  - Challenging recommended oral and intravenous voriconazole doses for improved
      efficacy and safety: population pharmacokinetics-based analysis of adult patients
      with invasive fungal infections.
AB  - BACKGROUND: Recommended oral voriconazole (VRC) doses are lower than intravenous
      doses. Because plasma concentrations impact efficacy and safety of therapy,
      optimizing individual drug exposure may improve these outcomes. METHODS: A
      population pharmacokinetic analysis (NONMEM) was performed on 505 plasma
      concentration measurements involving 55 patients with invasive mycoses who
      received recommended VRC doses. RESULTS: A 1-compartment model with first-order
      absorption and elimination best fitted the data. VRC clearance was 5.2 L/h, the
      volume of distribution was 92 L, the absorption rate constant was 1.1 hour(-1),
      and oral bioavailability was 0.63. Severe cholestasis decreased VRC elimination
      by 52%. A large interpatient variability was observed on clearance (coefficient
      of variation [CV], 40%) and bioavailability (CV 84%), and an interoccasion
      variability was observed on bioavailability (CV, 93%). Lack of response to
      therapy occurred in 12 of 55 patients (22%), and grade 3 neurotoxicity occurred
      in 5 of 55 patients (9%). A logistic multivariate regression analysis revealed an
      independent association between VRC trough concentrations and probability of
      response or neurotoxicity by identifying a therapeutic range of 1.5 mg/L (>85%
      probability of response) to 4.5 mg/L (<15% probability of neurotoxicity).
      Population-based simulations with the recommended 200 mg oral or 300 mg
      intravenous twice-daily regimens predicted probabilities of 49% and 87%,
      respectively, for achievement of 1.5 mg/L and of 8% and 37%, respectively, for
      achievement of 4.5 mg/L. With 300-400 mg twice-daily oral doses and 200-300 mg
      twice-daily intravenous doses, the predicted probabilities of achieving the lower
      target concentration were 68%-78% for the oral regimen and 70%-87% for the
      intravenous regimen, and the predicted probabilities of achieving the upper
      target concentration were 19%-29% for the oral regimen and 18%-37% for the
      intravenous regimen. CONCLUSIONS: Higher oral than intravenous VRC doses,
      followed by individualized adjustments based on measured plasma concentrations,
      improve achievement of the therapeutic target that maximizes the probability of
      therapeutic response and minimizes the probability of neurotoxicity. These
      findings challenge dose recommendations for VRC.

PMID- 22610926
TI  - Risk and prognosis of hospitalization for pneumonia among individuals with and
      without functioning renal transplants in Denmark: a population-based study.
AB  - BACKGROUND: Pneumonia is commonly diagnosed in immunosuppressed individuals. The
      risk and attributable morbidity of first hospitalization for pneumonia among
      renal transplant candidates and recipients were compared to those of population
      controls. METHODS: This population-based cohort study was conducted from 1
      January 1990 to 31 December 2009. Each member of a Danish population-based,
      nationwide cohort of first-time renal transplant recipients was matched by age
      and sex with up to 19 population controls. Information on hospital discharge
      diagnosis, emigration, and mortality was obtained from nationwide administrative
      databases. Individuals were observed from diagnosis of end-stage renal disease
      until first hospitalization for pneumonia. Risk factors were assessed by Poisson
      regression. RESULTS: The study included 4729 renal transplant candidates and
      recipients and 81 757 controls, providing 25 546 and 704 329 person-years of
      observation, respectively. Compared with population controls, the incidence rate
      ratio of first hospitalization for pneumonia was 10.2 (95% confidence interval
      [CI], 8.74-11.8) for renal transplant candidates, 8.02 (95% CI, 7.29-8.83) for
      renal transplant recipients, and 13.7 (95% CI, 11.5-16.3) for patients with graft
      loss. Among renal transplant recipients, risk factors included male sex, age >=50
      years, diabetes, chronic interstitial nephritis, polycystic kidney disease, and 1
      3 years of prior dialysis. Patients with pneumonia had a 78% (95% CI, 1.52-2.10)
      increased risk of graft loss. Thirty-day mortality of patients was comparable to
      that of the background population. CONCLUSIONS: The risk of first-time
      hospitalization for pneumonia remains high among renal transplant candidates and
      recipients. The attributable morbidity and mortality are of great clinical and
      public health concern and preventive measures are warranted.

PMID- 22610927
TI  - Placental malaria is associated with increased risk of nonmalaria infection
      during the first 18 months of life in a Beninese population.
AB  - BACKGROUND: Several studies have shown that the risk of malaria infection
      increases for children born to a mother with placental malaria infection. An
      immune tolerance phenomenon has been hypothesized. We addressed whether
      Plasmodium falciparum placental infection could additionally be associated with
      the risk of nonmalaria fevers in infants. METHODS: From 2007 to 2009, 553 infants
      were followed up from birth to 18 months in Benin. The occurrence of fever was
      actively screened by trained community workers. Malaria fevers (temperature >37.5
      degrees C with positive results of rapid diagnostic test or thick blood smear)
      were excluded from analysis. The association between placental malaria infection
      and the number of total, gastrointestinal, and respiratory febrile episodes was
      explored using binomial negative regression, with adjustment for maternal age,
      parity, parents' schooling, socioeconomic level, sex, village of birth, season of
      birth, prematurity, Apgar score and nutritional status. RESULTS: The prevalence
      of placental malaria infection was 11.2%. During a median follow-up of 17.8
      months, 624 nonmalaria fevers were registered. Placental malaria infection was
      associated with a higher risk of nonmalaria fever episodes (adjusted incidence
      rate ratio, 1.4; 95% confidence interval, 1.1-1.8) as well as gastrointestinal
      (1.6; 1.1-2.5) and respiratory (1.5; 1.1-2.1) febrile syndromes. The same pattern
      was obtained when considering consultations after the age of 6 months.
      CONCLUSIONS: These results suggest an association between placental malaria
      infection and nonmalaria infections in the first 18 months of life. Immune
      tolerance could lead to impaired immune development not specific to malaria
      infections in infants born to mothers with placental malaria infection, but
      further studies are needed.

PMID- 22610928
TI  - HIV replication and immune status are independent predictors of the risk of
      myocardial infarction in HIV-infected individuals.
AB  - BACKGROUND: Individuals infected by human immunodeficiency virus (HIV) have a
      higher risk of cardiovascular disease than the general population. The specific
      effects of virological and immunological parameters on the risk of myocardial
      infarction (MI) in HIV-infected individuals are debated. METHODS: We conducted a
      nested case-control study within the French Hospital Database on HIV. Case
      patients (n = 289) were patients who, between January 2000 and December 2006, had
      a prospectively recorded and validated first MI. Up to 5 HIV-infected controls (n
      = 884) matched for age, sex, and clinical center were selected, at random with
      replacement, among patients with no history of MI. Conditional logistic
      regression models were used to identify predictors of the risk of MI. RESULTS:
      Plasma HIV-1 RNA levels >50 copies/mL, a low CD4 T-cell nadir, and a high CD8 T
      cell count were independently associated with an increased risk of MI, with
      respective odds ratios of 1.51 (95% confidence interval, 1.09-2.10), 0.90 (.83
      .97) per log(2) unit, and 1.48 (1.01-2.18) for the highest tertile of CD8 T-cell
      counts (>1150 cells/mm(3)) compared with the lowest (<=760 cells/mm(3)).
      CONCLUSIONS: Independently of cardiovascular risk factors and antiretroviral
      therapy, HIV replication, a low CD4 T-cell nadir and a high current CD8 T-cell
      count are associated with an increased risk of MI in HIV-infected individuals.
      This suggests new paths for interventions to diminish the risk of MI in HIV
      infected patients.

PMID- 22610929
TI  - False-positive Aspergillus antigenemia due to blood product conditioning fluids.
AB  - The presence of Aspergillus antigens in blood transfusion components from
      different manufacturers was analyzed. Galacomannans were found in transfused
      patients, pooled platelet concentrates, fresh frozen plasma, and packed red cells
      collected using Fresenius Kabi bags. Galacomannans were also found in blood
      collection anticoagulant and platelet additive solution from this manufacturer.

PMID- 22610930
TI  - Doxycycline improves filarial lymphedema independent of active filarial
      infection: a randomized controlled trial.
AB  - BACKGROUND: The aim of this study was to determine whether improvement of
      filarial lymphedema (LE) by doxycycline is restricted to patients with ongoing
      infection (positive for circulating filarial antigen [CFA]), or whether the
      majority of CFA-negative patients with LE would also show a reduction in LE
      severity. METHODS: One hundred sixty-two Ghanaian participants with LE stage 1-5
      (Dreyer) were randomized blockwise into 2 groups (CFA positive or negative) and
      allocated to 3 treatment arms of 6 weeks: (1) amoxicillin (1000 mg/d), (2)
      doxycycline (200 mg/d), or (3) placebo matching doxycycline. All groups received
      standard hygiene morbidity management. The primary outcome was reduction of LE
      stages. Secondary outcomes included frequency of acute attacks and
      ultrasonographic assessment of skin thickness at the ankles. Parameters were
      assessed before treatment and after 3, 12, and 24 months. RESULTS: Doxycycline
      treated patients with LE stage 2-3 showed significant reductions in LE severity
      after 12 and 24 months, regardless of CFA status. Improvement was observed in
      43.9% of doxycycline-treated patients, compared with only 3.2% and 5.6% in the
      amoxicillin and placebo arms, respectively. Skin thickness was correlated with LE
      stage improvement. Both doxycycline and amoxicillin were able to reduce acute
      dermatolymphangioadenitis attacks. CONCLUSIONS: Doxycycline treatment improves
      mild to moderate LE independent of ongoing infection. This finding expands the
      benefits of doxycycline to the entire population of patients suffering from LE.
      Patients with LE stage 1-3 should benefit from a 6-week course of doxycycline
      every other year or yearly, which should be considered as an improved tool to
      manage morbidity in filarial LE. Clinical Trials Registration. ISRCTN 90861344.

PMID- 22610931
TI  - New treatment schemes for yaws: the path toward eradication.

PMID- 22610932
TI  - Sustained virological response to interferon plus ribavirin reduces non-liver
      related mortality in patients coinfected with HIV and Hepatitis C virus.
AB  - BACKGROUND: Sustained virological response (SVR) after therapy with interferon
      plus ribavirin reduces liver-related complications and mortality in patients
      coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV).
      We assessed the effect of SVR on HIV progression and mortality not related to
      liver disease. METHODS: An observational cohort study including consecutive
      HIV/HCV-coinfected patients treated with interferon plus ribavirin between 2000
      and 2008 in 19 centers in Spain. RESULTS: Of 1599 patients, 626 (39%) had an SVR.
      After a median follow-up of approximately 5 years, we confirmed that failure to
      achieve an SVR was associated with an increased risk of liver-related events and
      liver-related death. We also observed higher rates of the following events in
      nonresponders than in responders: AIDS-defining conditions (rate per 100 person
      years, 0.84 [95% confidence interval (CI), .59-1.10] vs 0.29 [.10-.48]; P= .003),
      non-liver-related deaths (0.65 [.42-.87] vs 0.16 [.02-.30]; P = .002), and non
      liver-related, non-AIDS-related deaths (0.55 [.34-.75] vs 0.16 [.02-.30]; P =
      .002). Cox regression analysis showed that the adjusted hazard ratios of new AIDS
      defining conditions, non-liver-related deaths, and non-liver-related, non-AIDS
      related deaths for nonresponders compared with responders were 1.90 (95% CI, .89
      4.10; P = .095), 3.19 (1.21-8.40; P = .019), and 2.85 (1.07-7.60; P = .036),
      respectively. CONCLUSIONS: Our findings suggest that eradication of HCV after
      therapy with interferon plus ribavirin in HIV/HCV-coinfected patients is
      associated not only with a reduction in liver-related events but also with a
      reduction in HIV progression and mortality not related to liver disease.

PMID- 22610933
TI  - A paradigm shift in drug development for treatment of rare multidrug-resistant
      gram-negative pathogens.
AB  - Multidrug-resistant (MDR) gram-negative pathogens pose a major threat to patients
      worldwide. Although the organisms remain relatively uncommon overall, their
      incidence is steadily increasing with associated increases in mortality and
      pharmacoeconomic impact. As evidenced by the dearth of new products in the
      pipeline or in clinical use, the conventional paradigm for the development of
      drugs against such pathogens is generally ineffectual. We advocate the need for a
      shift in the current paradigm and propose innovative development programs that
      involve implementation of a graduated approval process. The initial phase of the
      proposed regulatory paradigm includes early approval of a new drug based on a
      robust nonrandomized study, buttressed by data from concurrent controls and a
      pharmacokinetic-pharmacodynamic package generated from nonclinical studies. The
      postapproval commitment phase will include a randomized controlled trial, when
      disease prevalence permits, as well as continued assessment of risks and benefits
      under "real world" settings.

PMID- 22610934
TI  - An integrated process for removing the inhibitors of the prehydrolysis liquor of
      kraft-based dissolving pulp process via cationic polymer treatment.
AB  - The prehydrolysis liquor (PHL) of the kraft-based dissolving pulp production
      process contains various amounts of hemicelluloses that can be utilized in the
      production of value-added products. In this work, a new process was proposed for
      removing the inhibitors of PHL via employing a flocculation concept to facilitate
      the utilization of hemicelluloses. Lignin, lignocelluloses/cationic polymer
      complexes, and possibly ethanol are the main products of this process. This
      process has been experimentally evaluated with an industrially produced PHL and
      cationic polymers. The results showed that 16% of lignin, 19% of acetic acid, 43%
      of furfural, and insignificant amount of sugars were removed from PHL via
      pretreating PHL with acid and lime at pH 7. Furthermore, by adding 0.4-0.5 mg g(
      1) polydiallyldimethylammonium chloride (PDADMAC) or chitosan to the pretreated
      PHL, 12-14% acetic acid, 40-50% furfural, 5-6% monomeric sugars, and 25%
      oligomeric sugars were removed from the PHL. The complexes made from these
      components may be applied as organic fillers in various industries.
      Alternatively, by adding 1.2 or 1.4 mg g(-1) PDADMAC or chitosan to the
      pretreated PHL, 30 or 35% of lignin was removed, respectively, which induced
      complexes that could be used as a fuel source. The composition of the complexes
      formed was also determined in this work.

PMID- 22610935
TI  - Variation of bone collagen amino acid delta13C values in archaeological humans
      and fauna with different dietary regimes: developing frameworks of dietary
      discrimination.
AB  - We present bone collagen amino acid (AA) delta(13)C values for a range of
      archaeological samples representing four "benchmark" human diet groups (high
      marine protein consumers, high freshwater protein consumers, terrestrial C(3)
      consumers, and terrestrial C(4) consumers), a human population with an "unknown"
      diet, and ruminants. The aim is to establish an interpretive palaeodietary
      framework for bone collagen AA delta(13)C values, and to assess the extent to
      which AA delta(13)C values can provide additional dietary information to bulk
      collagen stable isotope analysis. Results are analyzed to determine the ability
      of those AAs for which we have a complete set, to discriminate between the diet
      groups. We show that very strong statistical discrimination is obtained for all
      interdiet group comparisons. This is often obvious from suitably chosen bivariate
      plots using delta(113)C values that have been normalized to compensate for
      interdiet group differences in bulk delta(13)C values. Bi-plots of non-normalized
      phenylalanine and valine delta(13)C values are useful for distinguishing aquatic
      diets (marine and freshwater) from terrestrial diets. Our interpretive framework
      uses multivariate statistics (e.g., discriminant analysis) to optimize the
      separation of the AA delta(13)C values of the "benchmark"' diet groups, and is
      capable of accurately assigning external samples to their expected diet groups.
      With a growing body of AA delta(13)C values, this method is likely to enhance
      palaeodietary research by allowing the "unknown" diets of populations under
      investigation to be statistically defined relative to the well-characterized or
      "known" diets of previously investigated populations.

PMID- 22610936
TI  - A self-help, positive goal-focused intervention to increase well-being in people
      with depression.
AB  - Self-help interventions are an accessible, first-step treatment for depression.
      Well-being interventions focus on increasing people's resources and bringing
      about positive feelings and behaviours and could enhance self-help interventions
      for depression by increasing well-being as well as reducing depression. The
      present study tested the effectiveness of a self-help, well-being intervention
      (Goal-setting and Planning, GAP) in both increasing well-being and reducing
      depression within a sample from a depression self-help organization. We used a
      cross-over design, with half of the participants allocated to GAP (n = 26) and
      half to a wait-list control group (n = 29). After 5 weeks, the wait-list control
      group also received GAP. Compared with wait-list controls, those allocated to GAP
      showed an overall positive change, with individual significant decreases in
      negative affect and trends towards significant decreases in depression and
      increases in positive affect and life satisfaction post-intervention. Within a
      cross-over design, the wait-list controls also received GAP. In the whole sample
      that received GAP, there were significant increases in positive affect and life
      satisfaction and significant decreases in negative affect and depression, post
      intervention and at 5-week follow-up, relative to baseline. These findings
      demonstrate that GAP is a useful intervention for people with symptoms of
      depression, influencing both levels of well-being and depressive symptoms.

PMID- 22610937
TI  - Phase II trial of temozolomide for leptomeningeal metastases in patients with
      solid tumors.
AB  - There is a current unmet medical need for treatment of leptomeningeal metastases
      (LMD). To analyze the efficacy and safety of systemic temozolomide (TMZ) for
      first-line treatment of patients with LMD associated with solid tumors, a phase
      II, non-randomized, multicenter, prospective study was conducted. The planned
      duration of treatment was a maximum of six cycles (24 weeks) or until
      unacceptable toxicity was reported. One cycle of oral TMZ (100 mg/m(2) daily)
      consisted of one week on treatment/one week off treatment for four weeks. The
      study was stopped early because of poor accrual. Nineteen patients (median age
      51(33-72); 32 % male) were enrolled. The LMD source was breast cancer (53 %) and
      non-small-cell lung cancer (37 %). Previous treatment was chemotherapy (100 %),
      surgery 74 %, radiotherapy 79 %, and hormone therapy 42 %. The average last dose
      of TMZ received by patients was 171 mg and only one patient required dose
      reduction. Three of 19 patients (15.8 %) had clinical benefit and 16 of 19
      patients (84.2 %) progressed. Of the two patients completing the study (six
      cycles, 24 weeks), one had a partial response and the other stable disease.
      Median survival was 43 days (95 % CI 28.7-57.3); there were 18 deaths. Median TTP
      was 28 days (95 % CI 14-42). The most common adverse event was vomiting (52.6 %);
      nine patients (47.4 %) reported at least one serious adverse event but only one
      episode of thrombocytopenia was drug related. Median Karnofsky score remained at
      or above 70 % throughout the study, and was 75 % at the end of the study. First
      line TMZ was well tolerated, and did not adversely affect the quality of life of
      patients with LMD. Future studies are needed to verify the efficacy results of
      this pilot trial.

PMID- 22610938
TI  - Leptomeningeal seeding in patients with brain metastases treated by gamma knife
      radiosurgery.
AB  - To characterize the development of leptomeningeal seeding (LMS) in patients with
      brain metastases after gamma knife radiosurgery (GKRS). Eight hundred and twenty
      seven patients that underwent GKRS as a part of an initial treatment plan for
      brain metastases between January 2002 and December 2010 were included in the
      study. Six hundred and fifty patients were treated with GKRS alone and 177
      patients received GKRS combined with upfront whole brain radiation therapy
      (WBRT). Actuarial curves for overall survival (OS) and the development of LMS
      were plotted using the Kaplan-Meier method. Median overall survival for all
      patients was 55 weeks (95 % CI, 47.8-62.2), and the overall incidence of LMS was
      5.3 %. The actuarial rates for LMS at 6 and 12 months were 3.1 and 5.8,
      respectively. Uni- and multivariate analysis suggested that breast cancer and a
      large number of metastases (n >= 4) are significant risk factors of LMS (P <
      0.05). Regarding treatment modalities, the addition of WBRT was found to have a
      significant impact on lowering the risk of LMS by multivariate analysis (P =
      0.045). LMS is an important pattern of CNS failure. The risk of LMS following
      GKRS may be associated with multiple lesions, breast cancer, and the omission of
      WBRT. Additional data from large-scale, randomized controlled trials are required
      to identify risk factors associated with the LMS more accurately.

PMID- 22610939
TI  - Primary tumor response to chemoradiotherapy in limited-disease small-cell lung
      cancer correlates with duration of brain-metastasis free survival.
AB  - The brain represents a crucial site of failure in limited-disease (LD) small-cell
      lung cancer (SCLC). However, no data about correlation between response of
      primary tumor to chemoradiotherapy (CRT) and brain metastases (BM)--free survival
      time in LD SCLC are available. A total of 125 LD SCLC patients with initial
      performance score of WHO 2-3 were successfully treated with CRT. Prophylactic
      cranial irradiation (PCI) was applied after complete response. Cranial MRI was
      performed in patients at initial diagnosis, in complete responders before PCI,
      and by individual symptoms. A total of 30 patients (24 %) developed BM after CRT;
      5 of them (17 %) developed BMs after PCI. Ten patients (33 %) show BM after
      complete, 5 (17 %) after partial and 15 (50 %) after non-response of primary
      tumor (p < 0.0001) to applied CRT. BM-free survival time for the entire cohort
      was 298 days (95 CI: 218-377): 567 days (95 CI: 322-811) in complete, 298 days
      (95 CI: 244-351) in partial and 252 days (95 CI: 217-286) in non-responders (p <
      0.0001). PCI prolonged BM-free survival time in complete responders: 640 days (95
      CI: 483-796) with PCI versus 482 days (95CI: 111-926) without PCI (p = 0.047)
      versus 273 days (95 CI: 243-302) for partial and non-responders. The duration of
      BM-free survival was shown to correlate with long-term outcome in the Pearson and
      Spearman's tests (p < 0.0001). The response of primary tumor to CRT strongly
      affects duration of BM-free survival in LD SCLC and should be considered by
      planning of the timing of PCI.

PMID- 22610941
TI  - Multi-zinc-expanded graphene patches: tetraradical versus diradical character.
AB  - Three classes of multi-Zn-expanded graphene patches in different shapes are
      computationally designed through introducing a Zn chain into the corresponding
      middle benzenoid chain. Both density functional theory and complete active space
      self-consistent field calculations predict that molecules of nnn-quasi-linear and
      nnn-slightly bent series have the open-shell broken-symmetry (BS) singlet
      diradical ground states, whereas those of n(n+1)n species possess quintet
      tetraradical as their ground state and become open-shell BS singlet tetraradicals
      when they are in a higher energy state. These results offer the first theoretical
      attempt to introduce multi-Zn into the small graphene patches to form Zn-expanded
      graphene patches, leading them to polyradical structures. This work provides an
      executable strategy to yield molecules which have stable polyradicaloid character
      and enhanced electronic properties of multi-Zn-expanded graphene patches.

PMID- 22610940
TI  - Imatinib mesylate treatment of recurrent meningiomas in preselected patients: a
      retrospective analysis.
AB  - Some unresectable and symptomatic meningiomas recur after conventional radiation
      therapy or stereotactic radiosurgery and are a therapeutic challenge. Evidence
      based data from medical therapy for patients with recurrent meningioma can be
      deemed insufficient. Because of the prevalent expression of PDGF receptors in
      meningiomas, the tyrosine kinase imatinib mesylate has attracted interest as a
      treatment option for this patient group. In this retrospective study we analyzed
      18 patients with recurrent meningiomas who were treated at our institution
      between 1996 and 2008. Nine patients with positive immunohistochemical staining
      of at least one of the PDGF receptors were given a daily oral dose of 400 mg
      imatinib mesylate as first, second, or third-line systemic therapy.
      Immunohistochemical staining was performed on formalin-fixed and paraffin
      embedded tumor tissue with antibodies against PDGFR-alpha and beta, c-Kit, Arg,
      and c-Abl. Imatinib mesylate at a dose of 400-800 mg/day was well tolerated. Of
      nine patients treated with imatinib, seven had stable disease and two had
      progressed at the first scan after three months. We observed no complete or
      partial responses, although prolonged disease stabilization with progression-free
      survival of 66.7 % at six months was observed. Overall median progression-free
      survival was 16 months. We conclude that single-agent imatinib mesylate might be
      a well-tolerated therapeutic option with high achievement of disease
      stabilization for preselected patients with recurrent meningiomas. Because of the
      small cohort, non-randomized design, and highly diverse patient population, we
      propose future prospective studies to validate our results.

PMID- 22610942
TI  - MCAM is a novel metastasis marker and regulates spreading, apoptosis and invasion
      of ovarian cancer cells.
AB  - Melanoma cell adhesion molecule (MCAM) is a cell adhesion molecule that is
      abnormally expressed in a variety of tumours and is closely associated with
      tumour metastasis. The role of MCAM in ovarian cancer development has not been
      fully studied. In this study, through immunohistochemical staining of ovarian
      cancer tissue samples and RNA interference to silence MCAM in ovarian cancer
      cells, we examined the impact of MCAM on the biological functions of ovarian
      cancer cells and attempted to reveal the role of MCAM in ovarian cancer
      development. Our results showed that MCAM expression was particularly high in
      metastatic ovarian cancers compared with other pathological types of ovarian
      epithelial tissues. After MCAM silencing in the MCAM high-expression ovarian
      cancer cell line SKOV-3, the cell apoptosis was increased, whereas the cell
      spreading and invasion were significantly reduced, which may be related with
      dysregulation of small RhoGTPase (RhoA and Cdc42).These results suggest that MCAM
      expression in ovarian cancer is highly correlated with the metastatic potential
      of the cancer. MCAM is likely to participate in the regulation of the Rho
      signalling pathway to protect ovarian cancer cells from apoptosis and promote
      their malignant invasion and metastasis. Therefore, MCAM can be used not only as
      a molecular marker to determine the prognosis of ovarian cancer but also as a
      therapeutic target in metastatic ovarian cancer.

PMID- 22610943
TI  - Burden of cancers in the valley of Kashmir: 5 year epidemiological study reveals
      a different scenario.
AB  - Cancer is a major burden worldwide but there are marked geographical variations
      in frequency and incidence overall. The aim of this study was to find the
      frequency and distribution of commonly occurring cancers in Kashmir, with
      particular emphasis on urinary bladder cancer. A total of 4,407 cases of
      histologically confirmed new cancer cases were registered at the Medical Records
      Department (MRD) of SKIMS from a period between January, 2005 and April 2010.
      Among 4407 cancers, 2,457 (55.7 %) were men and 1,950 (44.3 %) were women.
      Stomach cancer is the leading one with an average frequency of 19.2 % followed by
      esophagus and lung as 16.5 % and 14.6 %, respectively. Stomach (23 %) and lung
      (21 %) are the leading cancers in men while as esophageal cancer tops (18.3 %) in
      women followed by breast cancer (16.6 %). This distribution of cancer types is
      strikingly different from that in the rest of India where oropharyngeal cancer is
      most common form. Among urinogenital cancers, bladder cancer was observed to
      primarily affect Kashmiri population (5.9 %) followed by prostate cancer (2.1 %)
      and renal carcinoma (1.1 %). We conclude that Kashmir is a very high risk area of
      most commonly occurring cancers particularly cancers of gastrointestinal tract
      which comprise more than half the frequency of all the cancers.

PMID- 22610944
TI  - Rare inborn errors associated with chronic hepatitis B virus infection.
AB  - Chronic hepatitis B (CHB) is a major global health issue. The role of rare
      genetic variants in CHB has not been elucidated. We aimed to identify rare
      allelic variants predisposing to CHB. We performed exome sequencing in 50 CHB
      patients who had no identifiable risk factors for CHB and 40 controls who were
      healthy and hepatitis B surface antibody-positive, but had never received
      hepatitis B vaccination. We selected six rare variant alleles and followed up
      their association with disease status by Sanger sequencing in a case-control
      study comprising 1,728 CHB patients and 1,636 healthy controls. The latter had
      either not been immunized with hepatitis B vaccine or had uncertain vaccination
      status. Our results showed that transmembrane protein 2 p.Ser1254Asn, interferon
      alpha 2 p.Ala120Thr, its regulator NLR family member X1 p.Arg707Cys, and
      complement component 2 p.Glu318Asp were associated with CHB, with P values of
      <1.0 * 10(-7) , 2.76 * 10(-5) , 5.08 * 10(-5) , 2.78 * 10(-4) and odds ratios
      (ORs) of 2.45, 4.08, 2.34, and 1.97, respectively. The combined P value was <2.0
      * 10(-16) . As there has been no indication of immunological functions for the
      associated gene, transmembrane protein 2, we further studied its expression by
      immunohistochemistry, real-time polymerase chain reaction, and western blotting.
      Our results showed that it was strongly expressed by healthy hepatocytes, but its
      expression was reduced in liver tissues with CHB, hepatitis B viral (HBV) genome
      containing HepG2.2.15 cells, as compared with healthy liver tissues and non-HBV
      genome-containing HepG2 cells (P = 0.022 and 0.0036, respectively). CONCLUSION:
      We identified four missense mutations associated with CHB, our results providing
      evidence for rare inborn genetic defects that contribute to increased host
      susceptibility to CHB.

PMID- 22610947
TI  - Antipyretic and anticonvulsant activity of Polygonatum verticillatum: comparison
      of rhizomes and aerial parts.
AB  - The current study was undertaken to explore the antipyretic and anticonvulsant
      profile of the Polygonatum verticillatum in established pharmacological
      paradigms. The crude methanol extract of rhizomes (PR) and aerial parts (PA) of
      the plant were tested in Brewer's-yeast-induced pyrexia and pentylenetetrazole
      induced convulsion test. PR and PA both evoked prominent antipyretic activity (p
      < 0.01) in a dose-dependent manner during all assessment times at the dose of 50,
      100, and 200 mg/kg intraperitoneally. The protection elicited by PR (82.20%) at
      200 mg/kg was comparable with aspirin (88.48%) as a standard drug at 100 mg/kg.
      However, PA was less potent, and maximum protection was 64% at 200 mg/kg. Both PR
      and PA were devoid of any anticonvulsant activity. Our results demonstrated
      prominent evidence of antipyretic activity of P. verticillatum that is consistent
      with the folk uses of the plant. In addition from a biodiversity point of view,
      PA of the plant can also be used as an alternate of PR.

PMID- 22610945
TI  - E3 ubiquitin ligases in protein quality control mechanism.
AB  - In living cells, polypeptide chains emerging from ribosomes and preexisting
      polypeptide chains face constant threat of misfolding and aggregation. To prevent
      protein aggregation and to fulfill their biological activity, generally, protein
      must fold into its proper three-dimensional structure throughout their lifetimes.
      Eukaryotic cell possesses a quality control (QC) system to contend the problem of
      protein misfolding and aggregation. Cells achieve this functional QC system with
      the help of molecular chaperones and ubiquitin-proteasome system (UPS). The well
      conserved UPS regulates the stability of various proteins and maintains all
      essential cellular function through intracellular protein degradation. E3
      ubiquitin ligase enzyme determines specificity for degradation of certain
      substrates via UPS. New emerging evidences have provided considerable information
      that various E3 ubiquitin ligases play a major role in cellular QC mechanism and
      principally designated as QC E3 ubiquitin ligases. Nevertheless, very little is
      known about how E3 ubiquitin ligase maintains QC mechanism against abnormal
      proteins under various stress conditions. Here in this review, we highlight and
      discuss the functions of various E3 ubiquitin ligases implicated in protein QC
      mechanism. Improving our knowledge about such processes may provide opportunities
      to modulate protein QC mechanism in age-of-onset diseases that are caused by
      protein aggregation.

PMID- 22610948
TI  - Comparison of several attachment methods for human iPS, embryonic and adipose
      derived stem cells for tissue engineering.
AB  - As actual stem cell application quickly approaches tissue engineering and
      regenerative medicine, aspects such as cell attachment to scaffolds and
      biomaterials become important and are often overlooked. Here, we compare the
      effects of several attachment proteins on the adhesion, proliferation and stem
      cell identity of three promising human stem cell types: human adipose-derived
      stem cells (hASCs), human embryonic stem cells (hESCs) and human induced
      pluripotent stem cells (hiPSCs). Traditional tissue culture polystyrene plates
      (TCPS), Matrigel (Mat), laminin (Lam), fibronectin (FN) and poly-L-lysine (PLL)
      were investigated as attachment protein surfaces. For hASCs typically cultured on
      TCPS, laminin resulted in the greatest cell attachment and proliferation with
      largest cell areas, indicating favourability by cell spreading. However,
      mesenchymal stem cell markers indicative of hASCs were slightly more expressed on
      surfaces with lowest cell attachment, corresponding to increased cell roundness,
      a newly observed attribute in hASCs possibly indicating a more stem cell-like
      character. hESCs preferred Matrigel as a feeder-free culture surface.
      Interestingly, hiPSCs favoured laminin over Matrigel for colony expansion, shown
      by larger cell colony area and perimeter lengths, although cell numbers and stem
      cell marker expression level remained highest on Matrigel. These data provide a
      practical reference guide for selecting a suitable attachment method for using
      human induced pluripotent, embryonic or adipose stem cells in tissue engineering
      and regenerative medicine applications.

PMID- 22610949
TI  - Assessment of the genotoxic effects of organophosphorus insecticides phorate and
      trichlorfon in human lymphocytes.
AB  - In vitro genotoxic effects of organophosphorus insecticides Phorate (PHR) and
      Trichlorfon (TCF) were investigated using four genotoxicity endpoints. Different
      concentration ranges between 0.25-2.00 MUg mL(-1) of PHR and 2.34-37.50 MUg mL(
      1) of TCF were applied to lymphocytes. PHR and TCF significantly increased the
      frequency of chromosomal aberrations (except 2.34 MUg mL(-1) for TCF) and sister
      chromatid exchanges at all treatment times and concentrations. Most of the used
      concentrations induced a significant increase in the frequency of micronuclei.
      Furthermore, PHR and TCF significantly decreased the mitotic index at the higher
      concentrations after 24- and 48-h treatments. In the comet assay, PHR and TCF
      significantly increased the comet tail at all concentrations. However, the comet
      tail intensity was significantly increased at only the highest concentration of
      PHR and at all concentrations of TCF. According to these results, PHR and TCF
      possess clastogenic, mutagenic, and DNA damaging effects in human lymphocytes in
      vitro.

PMID- 22610950
TI  - A pilot study of attention bias subtypes: examining their relation to cognitive
      bias and their change following cognitive behavioral therapy.
AB  - OBJECTIVE: The present investigation examined (a) whether a clinical sample of
      individuals with social anxiety disorder (SAD) comprises two distinct groups
      based on attention bias for social threat (vigilant, avoidant), (b) the relation
      between attention bias and cognitive bias, specifically estimates of the
      probability that negative social events will occur (probability bias), and (c)
      specific changes in attention bias following cognitive behavioral therapy for
      social anxiety. METHOD: Participants were 24 individuals (nfemale = 7, nmale =
      17; mage = 41) who met diagnostic criteria for SAD and sought treatment for fear
      of public speaking. Hypotheses were tested using t tests, linear regression
      analyses, and a mixed design analysis of variance. RESULTS: Results yielded
      evidence of 2 pretreatment groups (vigilant and avoidant). There was a
      significant positive correlation between vigilance for (but not avoidance of)
      threat and probability bias (R = .561, p < .05). After 8 weeks of treatment, the
      direction of change in attention bias differed between groups, such that the
      vigilant group became less vigilant and the avoidant group became less avoidant,
      with the avoidant group showing a significant change in attention bias from
      pretreatment to posttreatment. CONCLUSIONS: These findings provide very
      preliminary support for the idea that individuals with SAD may differ according
      to type attention bias, avoidant or vigilant, as these biases changed in
      different ways following cognitive-behavioral therapy for SAD. Further research
      is needed to replicate and extend these findings in order to evaluate whether SAD
      comprises subgroups of attentional biases.

PMID- 22610946
TI  - Role of dopamine receptors in ADHD: a systematic meta-analysis.
AB  - The dopaminergic system plays a pivotal role in the central nervous system via
      its five diverse receptors (D1-D5). Dysfunction of dopaminergic system is
      implicated in many neuropsychological diseases, including attention deficit
      hyperactivity disorder (ADHD), a common mental disorder that prevalent in
      childhood. Understanding the relationship of five different dopamine (DA)
      receptors with ADHD will help us to elucidate different roles of these receptors
      and to develop therapeutic approaches of ADHD. This review summarized the ongoing
      research of DA receptor genes in ADHD pathogenesis and gathered the past
      published data with meta-analysis and revealed the high risk of DRD5, DRD2, and
      DRD4 polymorphisms in ADHD.

PMID- 22610951
TI  - Survival analysis of stage IV metastatic gastric cancer patients treated with
      HangAm-Plus.
AB  - OBJECTIVE: To evaluate the efficacy of HangAm-Plus (HAP) on stage IV metastatic
      gastric cancer by analyzing the treated patients' overall survival outcome.
      METHODS: Following the study eligibility, overall survival and one year survival
      rate of 44 stage IV metastatic gastric cancer patients who visited East-West
      Cancer Center (EWCC) were analyzed. The study consisted of two arms: HAP
      treatment only (n=18) and combined treatment of concurrent conventional
      chemotherapy and HAP (n=26). Patient characteristics by gender, age, surgical
      intervention, Eastern Cooperative Oncology Group (ECOG) score, treatment duration
      (< 4 weeks or [Symbol: see text]4 weeks), and lines of the chemotherapy received
      were assessed. Treatment related side effects were also assessed. RESULTS: The
      median survival of combined group was longer (10.0 months) than that of HAP group
      (5.1 months). One-year survival rate of combined treatment group and HAP group
      was 38.5%+/-9.5% and 33.3%+/-11.1%, respectively (P>0.05). One-year survival rate
      of those received more and less than 4-week treatment was 57.1%+/-18.7% and
      8.3%+/-8.0%, respectively (P=0.001). CONCLUSIONS: The study supports the safety
      and potential efficacy of HAP treatment in prevention of chemo-related side
      effects for stage IV metastatic gastric cancer treated with conventional
      chemotherapy. Further studies are needed to investigate and confirm the results
      before applying the treatment in clinical settings.

PMID- 22610952
TI  - The use of repeated measures analysis of variance to study the effect of phlegm
      heat syndrome on neurological deficits in patients with stroke.
AB  - OBJECTIVE: To explore the effect of phlegm-heat syndrome on the degree of
      neurological deficit and provide some data support for the correct recognition of
      the relationship between phlegm-heat syndrome and neurological deficits in stroke
      patients. METHODS: Clinical information were collected on 294 patients with acute
      ischemic stroke (AIS) whose syndrome and National Institute of Health stroke
      scale (NIHSS) score were checked at baseline (within the first 3-day admission)
      and at 7, 14, 28, and 90 days after admission to our clinical research centre. We
      explored the effect of phlegm-heat syndrome on the degree of neurological deficit
      following stroke by applying a repeated measures analysis of variance. RESULTS:
      Stroke patients with phlegm-heat syndrome had higher NIHSS score than patients
      without the syndrome (P <0.01), and there appeared to be a decrease in NIHSS
      score over time in all patients (P <0.01). CONCLUSIONS: Phlegm-heat syndrome in
      patients who have suffered stroke has an effect on the degree of neurological
      deficiency. Disappearance of phlegm-heat syndrome may improve the degree of
      neurological deficit observed in stroke patients.

PMID- 22610953
TI  - Relaxant effects of Aike Mixture on isolated bladder and prostatic urethral
      smooth muscle of rabbits.
AB  - OBJECTIVE: To observe the relaxant effect of Aike Mixture (AKM) on isolated
      bladder and prostatic urethral smooth muscle of rabbits. METHODS: The isolated
      bladder and prostatic urethral smooth muscle from male rabbits were placed in a
      Magnus bath and smooth muscle contraction was measured using a biological signal
      acquisition and analysis system. The effects of AKM in combination with
      methoxyamine, carbachol and CaCl2 on the contractile tension of muscle strips
      were determined by cumulative dosing. RESULTS: AKM dose-dependently reduced
      contractile tension of bladder trigone smooth muscle (r=0.831, P<0.05), reduced
      contractile wave amplitude (r=0.837, P<0.05) and decreased contractile frequency
      (r=-0.917, P<0.01). AKM significantly inhibited the increases in smooth muscle
      contraction induced by methoxyamine, carbachol and CaCl2. CONCLUSION: AKM dose
      dependently inhibited the contraction of rabbit isolated bladder and prostatic
      urethral smooth muscle by antagonizing alpha1-adrenergic receptors and M
      cholinergic receptors.

PMID- 22610954
TI  - Wilson's disease: update on integrated Chinese and Western medicine.
AB  - Wilson's disease (WD), or hepatolenticular degeneration, is an autosomal
      recessive inheritance disorder of copper metabolism caused by ATP7B gene
      mutation. As WD is an inherited disease of the nervous system that is not
      curable; early diagnosis with early and life-long treatment leads to better
      prognoses. Currently, the recommended treatment for WD is integrated Chinese and
      Western medicine. A number of studies indicate that treatment of integrative
      medicine can not only enforce the de-copper effect but also improve liver
      function, intelligence, and other factors. This article reviewed in detail the
      advantages of WD treated with Chinese and Western medicine together.

PMID- 22610955
TI  - Study of the distribution patterns of the constituent herbs in classical Chinese
      medicine prescriptions treating respiratory disease by data mining methods.
AB  - OBJECTIVE: To provide the distribution pattern and compatibility laws of the
      constituent herbs in prescriptions, for doctor's convenience to make decision in
      choosing correct herbs and prescriptions for treating respiratory disease.
      METHODS: Classical prescriptions treating respiratory disease were selected from
      authoritative prescription books. Data mining methods (frequent itemsets and
      association rules) were used to analyze the regular patterns and compatibility
      laws of the constituent herbs in the selected prescriptions. RESULTS: A total of
      562 prescriptions were selected to be studied. The result exhibited that, Radix
      glycyrrhizae was the most frequently used in 47.2% prescriptions, other
      frequently used were Semen armeniacae amarum, Fructus schisandrae Chinese, Herba
      ephedrae, and Radix ginseng. Herbal ephedrae was always coupled with Semen
      armeniacae amarum with the confidence of 73.3%, and many herbs were always
      accompanied by Radix glycyrrhizae with high confidence. More over, Fructus
      schisandrae Chinese, Herba ephedrae and Rhizoma pinelliae was most commonly used
      to treat cough, dyspnoea and associated sputum respectively besides Radix
      glycyrrhizae and Semen armeniacae amarum. The prescriptions treating dyspnoea
      often used double herb group of Herba ephedrae & Radix glycyrrhizae, while
      prescriptions treating sputum often used double herb group of Rhizoma pinelliae &
      Radix glycyrrhizae and Rhizoma pinelliae & Semen armeniacae amarum, triple herb
      groups of Rhizoma pinelliae & Semen armeniacae amarum & Radix glycyrrhizae and
      Pericarpium citri reticulatae & Rhizoma pinelliae & Radix glycyrrhizae.
      CONCLUSIONS: The prescriptions treating respiratory disease showed common
      compatibility laws in using herbs and special compatibility laws for treating
      different respiratory symptoms. These principle patterns and special
      compatibility laws reported here could be useful for doctors to choose correct
      herbs and prescriptions in treating respiratory disease.

PMID- 22610956
TI  - Comparative study on effects of Xiaoyao Powder and its modified prescription on
      plasma metabolomics of rats with chronic immobilization stress.
AB  - OBJECTIVE: To determine the changes in the levels of endogenous metabolites in
      rats with chronic immobilization stress (CIS) taking Xiaoyao Powder (XYP) and its
      modified prescription version, which lacks the volatile oils extracted from Herba
      Menthae. METHODS: Twenty-four experimental male SD rats were randomly divided
      into 4 groups of 6 rats each: control, model, XYP-1 (containing volatile oils
      from Herba Menthae), and XYP-2 (lacking volatile oils). All rats except control
      group rats were subjected to CIS 3 h per day for 21 consecutive days. Groups XYP
      1 and XYP-2 were given the extracted XYS with or without volatile oils (3.854
      g/kg; suspended in distilled water) via gavage 1 h before CIS each day for 21
      days. Rats were anesthetized using intraperitoneal injection of pentobarbital
      sodium (40 mg/kg) on the 22nd day. Observations were made using a Varian INOVA
      600 MHz NMR spectrometer at 27  degrees C. Carr-Purcell-Meiboom-Gill (CPMG) and
      longitudinal eddy-delay (LED) were applied, resulting in spectra showing only the
      signals from micro- and macro-metabolites. RESULTS: Compared to controls, rats
      subjected to CIS showed increased levels of plasma metabolites, such as acetic
      acid, choline, N-glycoprotein (NAC), saturated fatty acid, and blood sugars.
      Levels of low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and
      unsaturated fatty acids were decreased. The biochemical effects of XYS were
      characterized by elevated levels of VLDL, LDL, threonine, methionine, and
      glutamic acid in plasma. CONCLUSION: Some common and characteristic metabolites
      on the anti-CIS of XYP and its modified prescription were obtained. The
      metabolomics technology is a valuable tool and may be used to identify the
      specific metabolites and potential biomarkers of therapeutic effect of Chinese
      medicinal prescriptions.

PMID- 22610957
TI  - Influence of high blood glucose fluctuation on endothelial function of type 2
      diabetes mellitus rats and effects of Panax Quinquefolius Saponin of stem and
      leaf.
AB  - OBJECTIVE: To observe the influence of high blood glucose fluctuation on the
      endothelial function of type 2 diabetes mellitus (T2DM) rats and the effects of
      Panax Quinquefolius Saponin (PQS) of stem and leaf. METHODS: The T2DM model was
      induced by intraperitoneal injection of a small dose of streptozotocin (STZ, 35
      mg/kg) plus high fat and high caloric laboratory chow. Then, diabetic rats were
      divided into steady high blood glucose (SHG) group and fluctuant high blood
      glucose (FHG) group according to fasting blood glucose coefficient of variation
      (FBG-CV), and then, the FHG group rats were divided into 4 groups according to
      the level of FBG-CV and fasting blood glucose: PQS 30 mg/(kg.d) group, PQS 60
      mg/(kg.d) group, metformin hydrochloride control (MHC) group, and FHG control
      group, 10 in each group. Meanwhile, 10 rats without any treatment were used as
      normal control (NOR) group. Eight weeks later, the aortic arteries histology,
      plasma hepatocyte growth factor (HGF), and serum nitric oxide (NO), endothelin-1
      (ET-1), tumor necrosis factor alpha (TNF-alpha), and soluble intercellular
      adhesion molecule 1 (sICAM-1) were measured. RESULTS: In comparison with the NOR
      group, the level of plasma HGF and serum NO, ET-1 and TNF-alpha, and sICAM-1 in
      SHG and FHG control groups were all significantly increased (P<0.01); in
      comparison with the SHG group, plasma HGF and serum NO, ET-1, TNF-alpha, and
      sICAM-1 in FHG group were all significantly increased further (P<0.01 or P<0.05);
      meanwhile, in comparison with the FHG control group, the level of plasma HGF and
      serum NO, ET-1, TNF-alpha, and sICAM-1 in PQS and MHC groups were all decreased
      significantly (P<0.01). However, comparison of the aortic arteries histology
      among groups showed no significant differences either before or after treatment.
      CONCLUSION: Blood glucose fluctuation could facilitate the development of
      vascular endothelial dysfunction in T2DM rats, while PQS could improve the
      endothelial function of T2DM rats with high blood glucose fluctuation, which may
      be related to its effects of relieving vessel stress, decreasing vasoconstrictor
      ET-1 production, preventing compensated increase of NO, and reducing inflammatory
      reaction.

PMID- 22610959
TI  - A case study of Malayan tapir (Tapirus indicus) husbandry practice across 10
      zoological collections.
AB  - The Malayan, or Asian, tapir (Tapirus indicus) has a diminishing wild population
      and is becoming more common in captivity as zoos attempt to manage sustainable ex
      situ populations. Tapirs can be relatively easy to maintain and breed, but
      captive animals appear to suffer from reduced activity budgets, obesity, and poor
      public image. A questionnaire-based survey was designed and sent specifically to
      10 collections around the world that exhibit Malayan tapirs, with the aim of
      assessing husbandry regimes to determine prevalence of standardized practices as
      well as highlighting any key differences, and to showcase good practice, thus
      providing information beneficial to those maintaining this species in their zoo.
      Twenty-five animals were included in the survey from collections across four
      continents. The research's major conclusions show differing dietary make-up, with
      a lack of forage provision, contrasting with a diverse array of enrichment
      protocols used. Significant differences were noted between zoos for total amount
      of food offered (P = 0.000) as well as ratios of forage to concentrate pellet
      offered (P = 0.004). Comparing food offered to male and female tapirs with
      published requirements for an "average" of either gender shows not all zoos
      providing the amount suggested in husbandry guidelines. Intelligently designed
      and original enrichment was provided to all animals but differences between zoos
      were noted in the application and "usefulness" of enrichment for individual
      tapir. Overall, animals are benefiting from enrichment but welfare could be
      further improved via consistent feeding of ad libitum forage and regular use of
      browse as a constituent part of daily rations.

PMID- 22610958
TI  - Abnormal Savda syndrome: long-term consequences of emotional and physical stress
      on endocrine and immune activities in an animal model.
AB  - OBJECTIVE: To investigate the relationship between emotional status, cold-dry
      environment and long-term immune responses to the stressors, and the potential
      pathological mechanisms between causative factors of abnormal Savda syndrome
      (ASS) and the susceptibility to disease; thus to clarify the ASS, and secondly to
      identify the optimal ASS animal model for further studies on traditional Uighur
      therapeutical formulations. METHODS: Sixty mice were randomly and equally divided
      into 4 groups: control and 3 stress groups. The cold-dry environment was applied
      by keeping the mice in a climatic chamber. The emotional stress was induced by
      the application of the repeated electric foot-shocks in the electric foot-shock
      apparatus. The mice of the combined stress group underwent the repeated electric
      foot-shock treatment before being housed in the climatic chamber. The
      experimental routine was repeated for 21 days. In order to look into endocrine
      and immune stress responses, ELISA was used to determine the serum levels of the
      hormones corticotropin-releasing hormone (CRH), adrenocorticotropic hormone
      (ACTH), Beta-endorphin (beta-END) and corticosterone (CORT), of the cytokines
      interleukin 2 (IL-2), interleukin 6 (IL-6), interferon-gamma (INF-gamma) and
      tumor necrosis factor-alpha (TNF-alpha), and of the immunoglobulins
      immunoglobulin A (IgA), immunoglobulin M (IgM) and immunoglobulin G (IgG).
      Lymphocyte subsets were analyzed in duplicate in order to determine differences
      in the T cell ratio. RESULTS: In the cold-dry environment group, the serum levels
      of CRH, ACTH and CORT were significantly higher than those of the control group,
      whereas serum beta-END was not found significantly different. In both the
      repeated electric foot-shock group as well as in the combined stress group the
      serum levels of CRH, ACTH, beta-END and CORT were significantly higher. Compared
      to the control animals, the serum concentration of INF-gamma was significantly
      lower in all three different stress groups. The serum level of IL-2 was decreased
      in the combined stress group whereas the serum TNF-alpha level was significantly
      higher. The serum IgG level was significantly higher in all three stress groups,
      whereas the IgA level was lower in both chronic electric foot-shock group and
      combined stress group. The IgM level was found significantly higher in the
      combined stress group only. The percentage of CD4(+) cells in peripheral blood
      was dramatically decreased in mice exposed to colddry environment, chronic
      electric foot-shock and combined stress, whereas the percentage of the CD8(+)
      subset was not significantly different. The CD4(+)/CD8(+) ratios were markedly
      lower in both cold-dry environment group and combined stress group. CONCLUSIONS:
      Combined stress can cause hyperactivity of the HPA axis, and an imbalance in the
      Th1/Th2 cell subset may contribute to illustrate the partial pathological
      mechanisms of ASS. This study identified this animal model of a combination of
      physical and emotional stress as an optimal model for further studies on ASS and
      relative therapies.

PMID- 22610960
TI  - Gene expression of peripheral blood mononuclear cells as a tool in dietary
      intervention studies: What do we know so far?
AB  - Peripheral blood mononuclear cells (PBMCs) generally refer to monocytes and
      lymphocytes, representing cells of the innate and adaptive immune systems. PBMCs
      are a promising target tissue in the field of nutrigenomics because they seem to
      reflect the effects of dietary modifications at the level of gene expression. In
      this review, we describe and discuss the scientific literature concerning the use
      of gene expression at the mRNA level measured from PBMCs in dietary interventions
      studies conducted in humans. A search of literature was undertaken using PubMed
      (last assessed November 24, 2011) and 20 articles were selected for discussion.
      Currently, results from these studies showed that PBMCs seem to reflect liver
      environment and complement adipose tissue findings in transcriptomics. PBMC gene
      expression after dietary intervention studies can be used for studying the
      response of certain genes related to fatty acid and cholesterol metabolism, and
      to explore the response of dietary interventions in relation to inflammation.
      However, PBMC transcriptomics from dietary intervention studies have not resulted
      yet in clear confirmation of candidate genes related to disease risk. Use of
      microarray technology in larger well-designed dietary intervention studies is
      still needed for exploring PBMC potential in the field of nutrigenomics.

PMID- 22610961
TI  - In memoriam: Wylie Vale, Jr., Ph.D. (1941-2012).

PMID- 22610962
TI  - Animal models and the developmental origins of polycystic ovary syndrome:
      increasing evidence for the role of androgens in programming reproductive and
      metabolic dysfunction.

PMID- 22610963
TI  - Animals have a sex, and so should titles and methods sections of articles in
      Endocrinology.

PMID- 22610965
TI  - beta-adrenergic receptor stimulation transactivates protease-activated receptor 1
      via matrix metalloproteinase 13 in cardiac cells.
AB  - BACKGROUND: Chronic beta-adrenergic receptor (beta-AR) overstimulation, a
      hallmark of heart failure, is associated with increased cardiac expression of
      matrix metalloproteinases (MMPs). MMP-1 has been shown to cleave and activate the
      protease-activated receptor 1 (PAR1) in noncardiac cells. In the present study,
      we hypothesized that beta-AR stimulation would result in MMP-dependent PAR1
      transactivation in cardiac cells. METHODS AND RESULTS: beta-AR stimulation of
      neonatal rat ventricular myocytes (NRVMs) or cardiac fibroblasts with
      isoproterenol transduced with an alkaline phosphatase-tagged PAR1 elicited a
      significant increase in alkaline phosphatase-PAR1 cleavage. This isoproterenol
      dependent cleavage was significantly reduced by the broad-spectrum MMP inhibitor
      GM6001. Importantly, specific MMP-13 inhibitors also decreased alkaline
      phosphatase-PAR1 cleavage in isoproterenol-stimulated NRVMs, as well as in NRVMs
      stimulated with conditioned medium from isoproterenol-stimulated cardiac
      fibroblasts. Moreover, we found that recombinant MMP-13 stimulation cleaved
      alkaline phosphatase-PAR1 in NRVMs at DPRS(42)?(43)FLLRN. This also led to the
      activation of the ERK1/2 pathway through Galphaq in NRVMs and via the
      Galphaq/ErbB receptor pathways in cardiac fibroblasts. MMP-13 elicited similar
      levels of ERK1/2 activation but lower levels of generation of inositol phosphates
      in comparison to thrombin. Finally, we demonstrated that either PAR1 genetic
      ablation or pharmacological inhibition of MMP-13 prevented isoproterenol
      dependent cardiac dysfunction in mice. CONCLUSIONS: In this study, we demonstrate
      that beta-AR stimulation leads to MMP-13 transactivation of PAR1 in both cardiac
      fibroblasts and cardiomyocytes and that this likely contributes to pathological
      activation of Galphaq and ErbB receptor-dependent pathways in the heart. We
      propose that this mechanism may underlie the development of beta-AR
      overstimulation-dependent cardiac dysfunction.

PMID- 22610966
TI  - Middle Paleolithic human remains from the Gruta Da Oliveira (Torres Novas),
      Portugal.
AB  - Additional Middle Paleolithic human remains from layers 17, 18, and 22 of the
      Gruta da Oliveira, Portugal consist of a proximal manual phalanx 2 (Oliveira 5),
      a partial postcanine tooth (Oliveira 6), a humeral diaphysis (Oliveira 7), a
      distal mandibular molar (Oliveira 8), and a mandibular premolar (P(3) ) (Oliveira
      9). Oliveira 5, 6, and 8 are unremarkable for Late Pleistocene humans. The
      Oliveira 7 right humerus is moderately robust or the individual had the stocky
      body proportions of other European (including Iberian) Neandertals. The Oliveira
      9 P(3) has a large and symmetrical crown and lacks a distal accessory ridge and
      accessory lingual cusps, overlapping both Neandertal and recent human ranges of
      variation. It contrasts with at least recent human P(3) s in having relatively
      thin enamel. These join the Oliveira 1 to 4 remains in further documenting early
      MIS 3 Neandertal morphology in western Iberia.

PMID- 22610967
TI  - Absent ductus venosus--outcomes and implications from a tertiary centre.
AB  - BACKGROUND: Absent ductus venosus (ADV) has been reported as case reports and
      series with suggestions that the outcome is variable. The prognosis depended on
      the associated abnormalities with ADV and the type of umbilical venous drainage.
      METHODOLOGY: We performed a retrospective audit of all cases with ADV in our
      centre from 2004 to 2008 and prospectively collected cases from 2008 and analysed
      the associations and outcomes. To our 22 cases, we added 67 cases extracted from
      all the reported case series with isolated ADV in the English literature and
      analysed them together. RESULTS: Eight of the 22 cases in our centre had isolated
      ADV and all eight fetuses were live born with no adverse outcomes. This was
      similar when compiled with the 67 extracted cases. Of the 89 cases; 19 with
      isolated ADV had 100% survival. This was independent of the umbilical venous
      drainage in contrast to previous reports. The overall survival is 57% and 45%
      when there is an associated abnormality in the fetus. CONCLUSION: Isolated ADV
      has a favourable outcome regardless of the umbilical venous drainage.

PMID- 22610968
TI  - The role of diallyl sulfides and dipropyl sulfides in the in vitro antimicrobial
      activity of the essential oil of garlic, Allium sativum L., and leek, Allium
      porrum L.
AB  - The in vitro antibacterial activity of essential oils (EOs) obtained from fresh
      bulbs of garlic, Allium sativum L., and leek, Allium porrum L. ( Alliaceae), was
      studied. A. sativum (garlic) EO showed a good antimicrobial activity against
      Staphylococcus aureus (inhibition zone 14.8 mm), Pseudomonas aeruginosa
      (inhibition zone 21.1 mm), and Escherichia coli (inhibition zone 11.0 mm),
      whereas the EO of A. porrum (leek) had no antimicrobial activity. The main
      constituents of the garlic EO were diallyl monosulfide, diallyl disulfide (DADS),
      diallyl trisulfide, and diallyl tetrasulfide. The EO of A. porrum was
      characterized by the presence of dipropyl disulfide (DPDS), dipropyl trisulfide,
      and dipropyl tetrasulfide. The antimicrobial activities of the DADS and DPDS were
      also studied. The results obtained suggest that the presence of the allyl group
      is fundamental for the antimicrobial activity of these sulfide derivatives when
      they are present in Allium or in other species (DADS inhibition zone on S. aureus
      15.9 mm, P. aeruginosa 21.9 mm, E. coli 11.4 mm).

PMID- 22610969
TI  - Fluoride decreased osteoclastic bone resorption through the inhibition of NFATc1
      gene expression.
AB  - Over the past two decades, fluoride effects on osteoclasts have been evaluated;
      however, its molecular mechanisms remain unclear. In this study, we investigated
      the effect of fluoride on osteoclast formation, function, and regulation using
      osteoclasts formed from mice bone marrow macrophages treated with the receptor
      activator of NF-kappaB ligand and macrophage colony-stimulating factor. Our data
      showed that fluoride levels <= 8 mg/L had no effect on osteoclast formation;
      however, it significantly reduced osteoclast resorption at 0.5 mg/L. Fluoride
      activity on bone resorption occurred through the inhibition of nuclear factor of
      active T cells (NFAT) c1 expression. Furthermore, the expression of its
      downstream genes, including the dendritic cell-specific transmembrane protein, c
      Src, the d2 isoform of vacuolar (H+) ATPase v0 domain, matrix metalloproteinase
      9, and cathepsin K were decreased, leading to impaired osteoclast acidification,
      reduced secretion of proteolytic enzymes, and decreased bone resorption. In
      summary, our results suggested that fluoride has different roles in osteoclast
      formation and function. Fluoride <= 8 mg/L did not impact osteoclast formation;
      however, it significantly decreased the resorption activity of newly formed
      osteoclasts. The molecular mechanism of fluoride action may involve inhibition of
      NFATc1 and its downstream genes.

PMID- 22610970
TI  - Increasing access to your research published in AMBIO.

PMID- 22610971
TI  - Two-week joint mobilization intervention improves self-reported function, range
      of motion, and dynamic balance in those with chronic ankle instability.
AB  - We examined the effect of a 2-week anterior-to-posterior ankle joint mobilization
      intervention on weight-bearing dorsiflexion range of motion (ROM), dynamic
      balance, and self-reported function in subjects with chronic ankle instability
      (CAI). In this prospective cohort study, subjects received six Maitland Grade III
      anterior-to-posterior joint mobilization treatments over 2 weeks. Weight-bearing
      dorsiflexion ROM, the anterior, posteromedial, and posterolateral reach
      directions of the Star Excursion Balance Test (SEBT), and self-reported function
      on the Foot and Ankle Ability Measure (FAAM) were assessed 1 week before the
      intervention (baseline), prior to the first treatment (pre-intervention), 24-48 h
      following the final treatment (post-intervention), and 1 week later (1-week
      follow-up) in 12 adults (6 males and 6 females) with CAI. The results indicate
      that dorsiflexion ROM, reach distance in all directions of the SEBT, and the FAAM
      improved (p < 0.05 for all) in all measures following the intervention compared
      to those prior to the intervention. No differences were observed in any
      assessments between the baseline and pre-intervention measures or between the
      post-intervention and 1-week follow-up measures (p > 0.05). These results
      indicate that the joint mobilization intervention that targeted posterior talar
      glide was able to improve measures of function in adults with CAI for at least 1
      week.

PMID- 22610972
TI  - The centrosomal protein Tax1 binding protein 2 is a novel tumor suppressor in
      hepatocellular carcinoma regulated by cyclin-dependent kinase 2.
AB  - Deregulation of cellular-signaling pathways by the inactivation of tumor
      suppressor genes is one of the major causes of hepatocellular carcinoma (HCC). In
      this study, we identified Tax1 binding protein 2 (TAX1BP2) as a novel tumor
      suppressor gene in HCC. TAX1BP2 transcript was frequently underexpressed (42.2%
      with T/NT <0.5; P < 0.03) in HCCs, and underexpression of TAX1BP2 was associated
      with poorer overall survival rates in patients after surgical resection. An
      effector domain (ED) for TAX1BP2 tumor-suppressor activity was mapped to the
      amino-acid residues 267-756. Transient or stable expression of either full-length
      or ED of TAX1BP2 significantly suppressed HCC cell tumorigenicity through the
      activation of the p38/p53/p21 pathway. In contrast, silencing of TAX1BP2 by short
      interfering RNA remarkably suppressed the activation of the p38/p53/p21 pathway.
      Finally, phosphorylation of TAX1BP2 at serine-763 by cyclin-dependent kinase
      (CDK)2 abolished the TAX1BP2-mediated p38 activation and tumor-suppressive
      activity, indicating that TAX1BP2 can adapt CDK2 signaling to the p38/p53/p21
      pathway. CONCLUSION: Taken together, our data provide the first evidence that
      TAX1BP2 is a CDK2-regulated tumor-suppressor gene in HCC and is a novel activator
      of the p38/p53/p21 pathway.

PMID- 22610973
TI  - The role of self-construals in the link between anger regulation and
      externalizing problems in Korean American adolescents: testing a moderated
      mediation model.
AB  - OBJECTIVES: The present study had two primary aims: (a) to test the mediating
      role of anger regulation in the relation between family processes and
      externalizing problems; (b) to test the moderating role of culture (specifically,
      independent and interdependent self-construals) in the relation between anger
      regulation and symptomatology via a moderated mediation model. DESIGN: The sample
      comprised 166 Korean American adolescents (54.2% male), who were recruited from
      the Midwestern region of the United States. Adolescents' ages ranged from 11-15
      years old (M = 13.0 years; SD = 1.2). Cross-sectional data were collected via
      adolescent self-report questionnaires. RESULTS: Results indicated that the anger
      regulation variables (either individually or collectively) mediated the influence
      of family processes (i.e., family conflict, family cohesion, and father
      adolescent communication) on externalizing problems. Moreover, 2 indirect effects
      on externalizing problems were conditional upon adolescents' independent self
      construal. CONCLUSIONS: These findings suggest that clinical intervention efforts
      for addressing externalizing problems may benefit from targeting anger regulation
      strategies. However, such interventions should be tailored to consider cultural
      context, since mediation effects may be moderated by cultural factors such as
      self-construal.

PMID- 22610974
TI  - Engineered extracellular matrix components do not alter the immunomodulatory
      properties of mesenchymal stromal cells in vitro.
AB  - Mesenchymal stromal cells (MSCs) have emerged as promising candidates for
      regenerative therapies, including tissue engineering. Recently it has been
      reported that engineered extracellular matrix (ECM) components support the
      differentiation of MSCs into osteocytes and chondrocytes, indicating that ECM
      components may represent attractive carriers for MSC transplants to repair
      damaged tissues. However, little is known about the impact of engineered ECM
      components on the immunosuppressive properties of MSCs, which may essentially
      contribute to the prevention of allogeneic MSC transplant rejection. In the
      present study, we explored the potential of fibronectin, fibrillar collagen I,
      tropocollagen and collagen I/heparin to influence the immunosuppressive
      capacities of MSCs. We found that these ECM components do not modulate the
      capability of MSCs to inhibit the proliferation of anti-CD3/anti-CD28 antibody
      stimulated CD4+ and CD8+ T cells and of lymphocytes in a mixed lymphocyte
      reaction. In addition, the potential of MSCs to impair the production of
      immunostimulatory IL-12 and to improve the release of immunosuppressive IL-10 by
      6-sulpho LacNAc+ (slan) dendritic cells (DCs), representing a pro-inflammatory
      subset of human blood DCs, was not altered by the ECM components. Furthermore,
      ECM components do not influence the ability of MSCs to inhibit the slanDC-induced
      proliferation of CD4+ T cells. In conclusion, the used engineered ECMs maintain
      important immunosuppressive properties of MSCs, which support their suitablility
      as carriers for MSC transplants in tissue engineering.

PMID- 22610975
TI  - Occurrence and relative risk of stroke in incident and prevalent contemporary
      rheumatoid arthritis.
AB  - OBJECTIVE: In contrast with the wealth of data on ischaemic heart disease in
      rheumatoid arthritis (RA), data on stroke are scarce and contradictory. Despite
      the high clinical and aetiological relevance, there is no data regarding when (if
      ever) after RA diagnosis there is an increased risk. Our objective was to assess
      the risk of stroke (by subtype) in contemporary patients with RA, particularly in
      relation to time since RA diagnosis. METHODS: One incident RA cohort diagnosed
      between 1997 and 2009 (n=8077) and one nationwide prevalent RA cohort followed at
      Swedish rheumatology clinics between 2005 and 2009 ((n=39 065) were assembled).
      Each cohort member was matched to a general population comparator. Information on
      first-time hospitalisations for stroke up to 2009 was retrieved from the Swedish
      Patient Register. HR and 95% CI were estimated using Cox models. RESULTS: In
      prevalent unselected RA, the HR of ischaemic stroke was 1.29 (95% CI 1.18 to
      1.41). In the incident RA cohort, the overall risk increase was small and non
      significant (overall HR 1.11, 95% CI 0.95 to 1.30). When stratified by RA disease
      duration, an increased risk of ischaemic stroke was indeed detectable but only
      after 10 or more years since RA diagnosis (HR>10 years: 2.33, 95% CI 1.25 to
      4.34). Risk of haemorrhagic stroke was increased in prevalent but not in incident
      RA. CONCLUSION: The magnitude of stroke risk is lower than for ischaemic heart
      disease in RA, and the evolvement of this risk from RA diagnosis may be slower.
      This suggests different driving forces behind these two RA co-morbidities and has
      implications for the clinical follow-up of patients with RA.

PMID- 22610976
TI  - Phylogenetic origin and transcriptional regulation at the post-diauxic phase of
      SPI1, in Saccharomyces cerevisiae.
AB  - The gene SPI1, of Saccharomyces cerevisiae, encodes a cell wall protein that is
      induced in several stress conditions, particularly in the postdiauxic and
      stationary phases of growth. It has a paralogue, SED1, which shows some common
      features in expression regulation and in the null mutant phenotype. In this work
      we have identified homologues in other species of yeasts and filamentous fungi,
      and we have also elucidated some aspects of the origin of SPI1, by duplication
      and diversification of SED1. In terms of regulation, we have found that the
      expression in the post-diauxic phase is regulated by genes related to the PKA
      pathway and stress response (MSN2/4, YAK1, POP2, SOK2, PHD1, and PHO84) and by
      genes involved in the PKC pathway (WSC2, PKC1, and MPK1).

PMID- 22610977
TI  - Synergistic effects of amyloid peptides and lead on human neuroblastoma cells.
AB  - Aggregated amyloid peptides (AP), major components of senile plaques, have been
      considered to play a very important and crucial role in the development and neuro
      pathogenesis of Alzheimer's disease (AD). In the present in vitro, study the
      synergistic effects of Pb(2+), a heavy metal, and AP on the human neuroblastoma
      SH-SY5Y cells were investigated. The cells treated with Pb(2+) (0.01-10 MUM)
      alone exhibited a significant decrease in viability and IC(50) was 5 MUM. A
      similar decrease in viability was also observed when the cells were exposed to
      AP, Abeta1-40 (20-120 MUM) and Abeta25-35 (2.5-15 MUM) for 48 hrs. The IC(50)
      values were 60 MUM and 7.5 MUM for Abeta1-40 and Abeta25-35 respectively. To
      assess the synergistic effects the cells were exposed to IC(50) of both AP and
      Pb(2+), which resulted in further reduction of the viability. The study was
      extended to determine the lactate dehydrogenase (LDH) release to assess the
      cytotoxic effects, 8-isoprostane for extent of oxidative damage, COX 1 and 2 for
      inflammation related changes, p53 protein for DNA damage and protein kinases A
      and C for signal transduction. The data suggest that the toxic effects of AP were
      most potent in the presence of Pb(2+), resulting in an aggravated clinical
      pathological condition. This could be attributed to the oxidative stress,
      inflammation neuronal apoptosis and an alteration in the activities of the
      signaling enzymes.

PMID- 22610978
TI  - Copper levels in cholestatic infants on parenteral nutrition.
AB  - BACKGROUND: Copper levels are primarily regulated by biliary excretion. In
      cholestatic patients, there is a concern that the standard dose of copper in
      parenteral nutrition (PN) will result in excessive copper levels. This study
      looked retrospectively at cholestatic infants receiving PN with measured copper
      levels to ascertain if this is an actual clinical concern. METHODS: All infants
      from the previous 10 years receiving PN who had a copper level checked and were
      cholestatic were reviewed. Children with metabolic or liver structural anomalies
      were excluded from the review. Of the 28 patients found, 26 had gastrointestinal
      disorders, and 82% of these infants were on the standard PN copper dose (20
      ug/kg/d). RESULTS: Only one elevated copper level was found in a child with
      congenital heart disease, but 13 low levels were found. A smaller number of
      follow-up copper levels demonstrated that despite cholestasis, some patients
      require copper supplementation above standard recommendations. CONCLUSION:
      Cholestasis does not appear to impair copper excretion enough to result in
      elevated levels. In fact, infants with gastrointestinal disorders may require
      higher than standard dosing. Monitoring copper levels appears to be necessary to
      appropriately regulate copper dosing for cholestatic infants receiving PN.

PMID- 22610979
TI  - A rare case of hyperammonemia complication of high-protein parenteral nutrition.
AB  - Hyperammonemia is a metabolic derangement that can be potentially fatal. Primary
      hyperammonemia due to urea cycle enzyme deficiency is usually discovered in
      neonates but rarely can present in adulthood. Late-onset manifestations of urea
      cycle disorders can go unnoticed, until they become life threatening. The authors
      report a 28-year-old man who developed hyperammonemia in the hospital following
      parenteral nutrition (PN), leading to cerebral edema, which was fatal despite
      resolution of the hyperammonemia with cessation of PN and the use of continuous
      renal replacement therapy.

PMID- 22610980
TI  - Micronutrient, antioxidant, and oxidative stress status in children with severe
      cerebral palsy.
AB  - BACKGROUND: Markers indicative of micronutrient and antioxidant status in
      children with cerebral palsy (CP) were explored due to these children's well
      documented issues with food intake and the limited biochemical literature.
      MATERIALS AND METHODS: Children aged 4 to 12 years with marked CP (n = 24) and
      controls (n = 24) were recruited. The CP group represented orally (O) or
      enterally fed (E) children. Concentrations of red cell folate (RCF), magnesium,
      superoxide dismutase (SOD), glutathione reductase, and peroxidase were measured,
      as well as serum methylmalonic acid and vitamin C. Plasma hemoglobin, C-reactive
      protein, alpha-tocopherol, cholesterol, zinc, protein carbonyls, and total
      antioxidant capacity were also quantified. RESULTS: Data are reported as mean
      (SD) and z scores where values differ with age. Many similarities existed, but
      zinc z scores were reduced in O (-1.10 [0.83]) vs controls (-0.54 [0.54]) (P <
      .05), as well as for glutathione reductase in O (10.15 [1.69]) vs E (12.22
      [2.41]) and controls (11.51 [1.67]) (P < .05). RCF was greatly increased in E
      (1422 [70]) vs O (843 [80]) and controls (820 [43]) (P < .001). SOD was decreased
      in E (24.3 [1.4]) vs controls (27.0 [2.8]) (P < .05). CONCLUSION: Considering
      their vast impact on physiology, micronutrients should be routinely monitored in
      orally fed children with swallowing disorders and dietary limitations. Excessive
      intakes, particularly long term in enterally fed children, should also be
      monitored in view of their potential for competitive inhibition, particularly at
      high levels.

PMID- 22610981
TI  - An affective-cognitive processing model of post-traumatic growth.
AB  - A topic that has begun to attract interest from clinical psychologists and
      psychotherapists is post-traumatic growth. First, we provide a general overview
      of the field, setting out the historical development, main concepts, measurement
      issues and research findings. Second, we review evidence showing that the
      relationship between post-traumatic stress and post-traumatic growth is likely
      curvilinear. Third, a new affective-cognitive processing model of post-traumatic
      growth will be introduced in which post-traumatic stress is understood to be the
      engine of post-traumatic growth. Fourth, points of clinical intervention are
      described showing the ways in which therapists can facilitate post-traumatic
      growth.

PMID- 22610982
TI  - Nutritional B vitamin deficiency disrupts lipid metabolism causing accumulation
      of proatherogenic lipoproteins in the aorta adventitia of ApoE null mice.
AB  - SCOPE: Cardiovascular disease is the major cause of death in the world. Low
      dietary folate, elevated homocysteine, and high circulating cholesterol are risk
      factors. METHODS AND RESULTS: We investigated whether folate and/or B vitamin
      deficiency would change lipoprotein and fatty acid metabolism and lipid
      accumulation in the aorta adventitia of ApoE null mice. Mice (n = 10 per group)
      were fed a control (C; 4%) or high saturated fat (HF; 21%), and high cholesterol
      (0.15%) diet for 16 weeks. Folate (F-) or folate, B6 and B12 deficiency (F-B-)
      were imposed on these diets. Feeding a HF diet increased plasma and liver total
      cholesterol and HDL cholesterol (two- to threefold; p < 0.05). Total cholesterol
      increased (twofold; p < 0.05) in aorta adventitial lipid in response to HF.
      Feeding a diet depleted of folate and B vitamins (F-B-) significantly increased
      cholesterol accumulation in both liver and aorta adventitial lipid (approximately
      50-70%; p < 0.05). Moreover, the proportions of fatty acids in hepatic and
      adventitial lipid was significantly changed by B vitamin depletion, measured as
      an increase in saturated fatty acids (approximately 15%) and a decrease
      (approximately 11%) in monounsaturated fatty acids (p < 0.05). CONCLUSION: B
      vitamin deficiency perturbs lipid metabolism in ApoE null mice, causing
      accumulation of proatherogenic cholesterol and fatty acids in the aorta
      adventitia.

PMID- 22610983
TI  - Different profiles of hepatic alkoxyresorufin O-dealkylase activities in small
      rodents.
AB  - The aims of the present study were to determine cytochrome P450 enzyme activity
      in six strains of experimental rodents (n = 5/sex/species): ICR, C57BL/6 and
      DBA/2 mice; Sprague Dawley and Wistar rats; and Dunkin Hartley guinea pigs. After
      animals were treated with the typical inducers beta-naphthoflavone (BNF),
      dexamethasone (DEX) and phenobarbital (PB), the levels of O-dealkylation of
      ethoxyresorufin (EROD), methoxyresorufin (MROD), pentoxyresorufin (PROD) and
      benzyloxyresorufin (BROD) activity were determined using responsive catalytic
      reactions to study CYP1A1, CYP1A2 and CYP2B, respectively. A maximal induction of
      EROD and MROD was found in BNF-treated animals from all strains (2.4- to 15.1
      fold) except DBA/2 (0.9- to 1.8-fold). C57BL/6 mice had the strongest BNF-induced
      EROD (15.1-fold) and MROD (8.3-fold) activities. No differences in BNF-induced
      EROD and MROD activities were observed between males and females. However, the
      EROD activity of Wistar rats and the MROD activity of Sprague Dawley rats were
      higher in males than females. DEX induced PROD activity only in mice (1.3- to 7.1
      fold), but not in rats and guinea pigs (0.2- to 1.1-fold). However, induction of
      BROD activity was found in DEX-treated mice and rats (1.5 to 12.5-fold), but not
      in guinea pigs (0.3 to 0.4-fold). PB caused a significant elevation of PROD (1.7-
      to 10.4-fold) and BROD (31- to 13.2-fold) activities in all the animals. PB
      induced BROD activity was higher in females than males in Sprague Dawley rats.
      These observations strongly suggest that the choice of experimental animal
      strain, species and inducer is of critical importance for studies of drug
      metabolism and interaction.

PMID- 22610984
TI  - p-Cresol sulfate and indoxyl sulfate induce similar cellular inflammatory gene
      expressions in cultured proximal renal tubular cells.
AB  - BACKGROUND: p-Cresol sulfate (PCS) and indoxyl sulfate (IS) have important roles
      in the kidney injury. The aim of this study was to determine the inflammatory
      response to PCS and IS. METHODS: Cultured mouse proximal renal tubular cells were
      treated with PCS or IS and analyzed by polymerase chain reaction array with an
      inflammation and immune panel. Gene annotation enrichment and functional
      annotation clustering were analyzed with the Database for Annotation,
      Visualization, and Integrated Discovery (DAVID). Functional networks of the
      target genes were analyzed with the algorithm GeneMANIA. RESULTS: PCS and IS
      increased the expression of inflammation associated genes. Sixteen upregulated
      gene clusters of cells treated with PCS or IS were found. The major cytokines in
      the functional networks generated by PCS or IS treatment were Tgfb1, Fasl,
      Il6/15, Il15, Csf1/3 and Cxcl10. The major intracellular signal triggered by PCS
      or IS included Stats, Smads, Nfkb2, Ikbkb, Bcl2 and Bax. In both PCS- and IS
      treated cells, Col4a5, Cxc10, Fasl, Stat1 and Ikbkb were the target genes in the
      predicted molecular functional networks connected to Tgfb1. CONCLUSIONS: PCS and
      IS stimulate significant cellular inflammation. Similar immune and cellular
      inflammatory responses were induced by PCS or IS on cultured proximal renal
      tubular cells.

PMID- 22610985
TI  - The clinical significance of hyperkalaemia-associated repolarization
      abnormalities in end-stage renal disease.
AB  - BACKGROUND: Hyperkalaemia is a common potentially fatal complication of chronic
      kidney disease (CKD). It may manifest as electrocardiogram (ECG) changes, the
      earliest of which is T-wave 'tenting'. However, this occurs in less than half of
      episodes of hyperkalaemia. The aim of this study was to determine what other
      clinical features relate to the probability of T-wave tenting; and if there is a
      longer-term survival difference between patients who develop tenting and those
      who do not. METHOD: One hundred and forty-five patients with end-stage renal
      disease who had standard 12-lead ECG and concurrent serum potassium measurement
      were enrolled. The presence of tenting and the ratio of the amplitude of the
      tallest precordial T-wave and R-wave were determined (T:R). RESULTS: Tenting was
      as common in normal range serum potassium as hyperkalaemia (33 versus 31%) and
      less common than in left ventricular hypertrophy (44%). T:R was less sensitive
      (24 versus 33%) but more specific (85 versus 67%) than tenting at correctly
      identifying hyperkalaemia >= 6.0 mmol/L. Tenting became less common with
      increasing age. Dialysis patients were more likely to show increased T:R that pre
      dialysis Stage 5 CKD. Elevated T:R was not associated with worse cardiovascular
      outcome but was associated with increased risk of sudden death over a mean follow
      up of 3.8 years (hazard ratio = 8.3, P = 0.021). CONCLUSIONS: The reason for the
      variability in T-wave changes is not clear. The ratio of precordial T-wave to R
      wave amplitude is a more specific measure than tenting but both are poorly
      sensitive at detecting hyperkalaemia. The greater risk for sudden death may
      represent a susceptibility to cardiac arrhythmia during repolarization.

PMID- 22610986
TI  - Human proximal tubule epithelial cells modulate autologous dendritic cell
      function.
AB  - BACKGROUND: We have previously demonstrated that human kidney proximal tubule
      epithelial cells (PTEC) are able to modulate autologous T and B lymphocyte
      responses. It is well established that dendritic cells (DC) are responsible for
      the initiation and direction of adaptive immune responses and that these cells
      occur in the renal interstitium in close apposition to PTEC under inflammatory
      disease settings. However, there is no information regarding the interaction of
      PTEC with DC in an autologous human context. METHODS: Human monocytes were
      differentiated into monocyte-derived DC (MoDC) in the absence or presence of
      primary autologous activated PTEC and matured with polyinosinic:polycytidylic
      acid [poly(I:C)], while purified, pre-formed myeloid blood DC (CD1c(+) BDC) were
      cultured with autologous activated PTEC in the absence or presence of poly(I:C)
      stimulation. DC responses were monitored by surface antigen expression, cytokine
      secretion, antigen uptake capacity and allogeneic T-cell-stimulatory ability.
      RESULTS: The presence of autologous activated PTEC inhibited the differentiation
      of monocytes to MoDC. Furthermore, MoDC differentiated in the presence of PTEC
      displayed an immature surface phenotype, efficient phagocytic capacity and, upon
      poly(I:C) stimulation, secreted low levels of pro-inflammatory cytokine
      interleukin (IL)-12p70, high levels of anti-inflammatory cytokine IL-10 and
      induced weak Th1 responses. Similarly, pre-formed CD1c(+) BDC matured in the
      presence of PTEC exhibited an immature tolerogenic surface phenotype, strong
      endocytic and phagocytic ability and stimulated significantly attenuated T-cell
      proliferative responses. CONCLUSIONS: Our data suggest that activated PTEC
      regulate human autologous immunity via complex interactions with DC. The ability
      of PTEC to modulate autologous DC function has important implications for the
      dampening of pro-inflammatory immune responses within the tubulointerstitium in
      renal injuries. Further dissection of the mechanisms of PTEC modulation of
      autologous immune responses may offer targets for therapeutic intervention in
      renal medicine.

PMID- 22610987
TI  - Hypomagnesaemia, the kidney and the vessels.

PMID- 22610988
TI  - Could Pentoxifylline (PTX) be a promising agent to reduce the systemic
      inflammation in hemodialysis patients?

PMID- 22610989
TI  - Outcome of patients with membranous lupus nephritis in Cape Town South Africa.
AB  - BACKGROUND: The kidney is one of the major target organs affected by systemic
      lupus erythematosus. Although proliferative forms of lupus nephritis (LN) occur
      more frequently than membranous LN (MLN), the latter appears to have a more
      favourable outcome. Only a few studies have reported the outcome of patients with
      MLN. METHODS: A retrospective analysis of patients with biopsy-confirmed MLN from
      a single centre in South Africa treated from 1st January 2000 to 31st December
      2009. RESULTS: The mean age of the patients (n = 42) at onset of LN was 35.0 +/-
      12.8 years with 73.8% of the patients being of mixed ancestry (coloureds). Eleven
      patients (26.2%) reached the composite end point of death or end-stage renal
      disease or persistent doubling of serum creatinine. The overall median survival
      and median renal survival times were 82.3 +/- 15.5 months (95% confidence
      interval 52.0-112.6) and 84.5 +/- 15.0 months (55.1-113.8), respectively. Also, 5
      year event-free survival and renal survival were 64 and 71%, respectively. On
      multivariate analysis, systolic blood pressure (BP) during follow-up (P = 0.029),
      diastolic BP during follow-up (P = 0.020) and attainment of complete remission at
      6 months (P = 0.033) were factors associated with the composite end points.
      Although treatment with chloroquine was not significantly associated with the
      composite end points (P = 0.05), we found that patients who received chloroquine
      had better renal survival compared with those who did not (P = 0.007).
      CONCLUSIONS: The outcome of patients with MLN in Cape Town is poorer than for
      similar patients reported from other centres across the world. Better BP control
      may significantly influence outcome of disease in these patients.

PMID- 22610990
TI  - Sonographic assessment of normal and abnormal patterns of fetal cerebral
      lamination.
AB  - OBJECTIVES: Prenatal development of the brain is characterized by gestational age
      specific changes in the laminar structure of the brain parenchyma before 30
      gestational weeks. Cerebral lamination patterns of normal fetal brain development
      have been described histologically, by postmortem in-vitro magnetic resonance
      imaging (MRI) and by in-vivo fetal MRI. The purpose of this study was to evaluate
      the sonographic appearance of laminar organization of the cerebral wall in normal
      and abnormal brain development. METHODS: This was a retrospective study of
      ultrasound findings in 92 normal fetuses and 68 fetuses with abnormal cerebral
      lamination patterns for gestational age, at 17-38 weeks' gestation. We
      investigated the visibility of the subplate zone relative to the intermediate
      zone and correlated characteristic sonographic findings of cerebral lamination
      with gestational age in order to evaluate transient structures. RESULTS: In the
      normal cohort, the subplate zone-intermediate zone interface was identified as
      early as 17 weeks, and in all 57 fetuses examined up to 28 weeks. In all of these
      fetuses, the subplate zone appeared anechoic and the intermediate zone appeared
      homogeneously more echogenic than did the subplate zone. In the 22 fetuses
      between 28 and 34 weeks, there was a transition period when lamination
      disappeared in a variable fashion. The subplate zone-intermediate zone interface
      was not identified in any fetus after 34 weeks (n=13). There were three patterns
      of abnormal cerebral lamination: (1) no normal laminar pattern before 28 weeks
      (n=32), in association with severe ventriculomegaly, diffuse ischemia,
      microcephaly, teratogen exposure or lissencephaly; (2) focal disruption of
      lamination before 28 weeks (n=24), associated with hemorrhage, porencephaly,
      stroke, migrational abnormalities, thanatophoric dysplasia, meningomyelocele or
      encephalocele; (3) increased prominence and echogenicity of the intermediate zone
      before 28 weeks and/or persistence of a laminar pattern beyond 33 weeks (n=10),
      associated with Type 1 lissencephaly or CMV infection. There was a mixed
      focal/diffuse pattern in two fetuses. In CMV infection, the earliest indication
      of the infection was focal heterogeneity and increased echogenicity of the
      intermediate zone, which predated the development of microcephaly,
      ventriculomegaly and intracranial calcification. CONCLUSIONS: The fetal subplate
      and intermediate zones can be demonstrated reliably on routine sonography before
      28 weeks and disappear after 34 weeks. These findings represent normal
      gestational age-dependent transient laminar patterns of cerebral development and
      are consistent with histological studies. Abnormal fetal cerebral lamination
      patterns for gestational age are also visible on sonography, and may indicate
      abnormal brain development.

PMID- 22610991
TI  - Arterial input function measurements for bolus tracking perfusion imaging in the
      brain.
AB  - Imaging of cerebral perfusion by tracking the first passage of an exogenous
      paramagnetic contrast agent (termed dynamic susceptibility contrast, MRI) has
      been used in the clinical practice for about a decade. However, the primary goal
      of dynamic susceptibility contrast MRI to directly quantify the local cerebral
      blood flow remains elusive. The major challenge of dynamic susceptibility
      contrast MRI is to measure the contrast inflow to the brain, i.e., the arterial
      input function. The measurement is complicated by the limited dynamic range of
      MRI pulse sequences that are optimized for a good contrast in brain tissue but
      are suboptimal for a much higher tracer concentration in arterial blood. In this
      work, we suggest a novel method for direct arterial input function
      quantification. The arterial input function is measured in the carotid arteries
      with a dedicated plug-in to the conventional pulse sequence to enable resolution
      of T(2) on the order of a millisecond. The new technique is compatible with the
      clinical measurement protocols. Applied to the pig model (N = 13), the method
      demonstrates robustness of the arterial input function measurement. The cardiac
      output and cerebral blood volume, obtained without adjustable parameters, agree
      well with positron emission tomography measurements and values found in the
      literature.

PMID- 22610992
TI  - Perinatal exposure to Di-(2-ethylhexyl)-Phthalate leads to cognitive dysfunction
      and phospho-tau level increase in aged rats.
AB  - Di-(2-ethylhexyl)-Phthalate (DEHP) can affect glucose and insulin homeostasis in
      periphery and lead to insulin resistance, especially exposure of DEHP during
      critical developmental period. Given the potential relationship between insulin
      resistance and pathogenesis of Alzheimer's disease (AD) in elderly life, we
      investigated the relationship between perinatal DEHP exposure and AD
      pathogenesis. Our results suggested that perinatal exposure to DEHP can affect
      the expression of insulin and insulin-Akt- GSK-3beta signal pathway in
      hippocampus. Furthermore, impaired cognitive ability and increased level of
      phospho-Tau was observed in DEHP-exposed rat offspring (1.25 +/- 0.11 vs. 0.47 +/
      0.07, P < 0.05). The present study demonstrates that perinatal exposure to DEHP
      may be a potential risk factor for AD pathogenesis associated with insulin
      resistance and insulin metabolism disorder in the hippocampus.

PMID- 22610993
TI  - Resolvins E1 and D1 inhibit interstitial fibrosis in the obstructed kidney via
      inhibition of local fibroblast proliferation.
AB  - Resolvin E1 (RvE1) is a naturally occurring lipid-derived mediator generated
      during the resolution of inflammation. The anti-inflammatory effects of RvE1 have
      been demonstrated in a variety of disease settings; however, it is not known
      whether RvE1 may also exert direct anti-fibrotic effects. We examined the
      potential anti-fibrotic actions of RvE1 in the mouse obstructed kidney-a model in
      which tissue fibrosis is driven by unilateral ureteric obstruction (UUO), an
      irreversible, non-immune insult. Administration of RvE1 (300 ng/day) to mice
      significantly reduced accumulation of alpha-smooth muscle actin (SMA)(+)
      myofibroblasts and the deposition of collagen IV on day 6 after UUO. This
      protective effect was associated with a marked reduction of myofibroblast
      proliferation on days 2, 4 and 6 after UUO. RvE1 treatment also inhibited
      production of the major fibroblast mitogen, platelet-derived growth factor-BB
      (PDGF-BB), in the obstructed kidney. Acute resolvin treatment over days 2-4 after
      UUO also had a profound inhibitory effect upon myofibroblast proliferation
      without affecting the PDGF expression, suggesting a direct effect upon fibroblast
      proliferation. In vitro studies established that RvE1 can directly inhibit PDGF
      BB-induced proliferation in primary mouse fibroblasts. RvE1 induced transient,
      but not sustained, activation of the pro-proliferative ERK and AKT signalling
      pathways. Of note, RvE1 inhibited the sustained activation of ERK and AKT
      pathways seen in response to PDGF stimulation, thereby preventing up-regulation
      of molecules required for progression through the cell cycle (c-Myc, cyclin D)
      and down-regulation of inhibitors of cell cycle progression (p21, cip1). Finally,
      siRNA-based knock-down studies showed that the RvE1 receptor, ChemR23, is
      required for the anti-proliferative actions of RvE1 in cultured fibroblasts. In
      conclusion, this study demonstrates that RvE1 can inhibit fibroblast
      proliferation in vivo and in vitro, identifying RvE1 as a novel anti-fibrotic
      therapy.

PMID- 22610994
TI  - Charge state coalescence during electrospray ionization improves peptide
      identification by tandem mass spectrometry.
AB  - We report the effects of supercharging reagents dimethyl sulphoxide (DMSO) and m
      nitrobenzyl alcohol (m-NBA) applied to untargeted peptide identification, with
      special emphasis on non-tryptic peptides. Peptides generated from a mixture of
      five standard proteins digested with trypsin, elastase, or pepsin were separated
      with nanoflow liquid chromatography using mobile phases modified with either 5%
      DMSO or 0.1%m-NBA. Eluting peptides were ionized by online electrospray and
      sequenced by both CID and ETD using data-dependent MS/MS. Statistically
      significant improvements in peptide identifications were observed with DMSO co
      solvent. In order to understand this observation, we assessed the effects of
      supercharging reagents on the chromatographic separation and the electrospray
      quality. The increase in identifications was not due to supercharging, which was
      greater for the 0.1%m-NBA co-solvent and not observed for the 5.0% DMSO co
      solvent. The improved MS/MS efficiency using the DMSO modified mobile phase
      appeared to result from charge state coalescence.

PMID- 22610995
TI  - Impact of weight-loss surgery and diabetes status on serum ALT levels.
AB  - BACKGROUND: Alanine aminotransferase (ALT) is used to detect non-alcoholic fatty
      liver disease and has been associated with increased risk of metabolic syndrome
      and type II diabetes mellitus (T2DM). Bariatric procedures result in significant
      weight loss and a rapid resolution of T2DM. We aimed to study the impact of
      bariatric interventions on ALT levels in patients with or without T2DM and
      compare this effect between different types of weight-loss procedures. METHODS:
      We reviewed 756 patients undergoing bariatric surgery. Demographics, co
      morbidities, baseline and post-operative ALT and HbA1C levels, weight-loss data,
      and diabetes status were recorded. ALT levels were compared between different
      procedures and between diabetic and non-diabetic patients. Chi-square test,
      ANOVA, and t test were used to evaluate outcomes. RESULTS: Males and diabetics
      had significantly higher ALT at baseline. Both Roux-en-Y gastric bypass surgery
      (RYGB) and laparoscopic adjustable gastric banding (LAGB) resulted in significant
      reduction in ALT levels beginning at the third post-operative month (20 and 17 %,
      respectively, compared to baseline, p < 0.001). ALT remained at the new low level
      up to year 3 after surgery. The degree of reduction was similar for both
      procedures and was independent of the degree of weight loss. In diabetics, ALT
      reduction was associated with improvement in disease; but in T2DM patients who
      remained on insulin, ALT remained elevated. CONCLUSIONS: RYGB and LAGB decrease
      ALT levels to the same degree and independent of weight loss. Our data confirm
      higher ALT in diabetics and demonstrate a rapid normalization after bariatric
      surgery with a simultaneous decrease in HbA1C. These results suggest that ALT may
      be used as a marker of metabolic improvement after bariatric surgery.

PMID- 22610996
TI  - Tracing hepatitis B virus to the 16th century in a Korean mummy.
AB  - A rare find of a mummified child from the 16th century AD, in Korea, with
      relatively preserved organs, enabled a search for ancient hepatitis B virus
      (aHBV) DNA sequences from laparoscopic-derived liver biopsies. Analysis of the
      complete aHBV genome (3,215 base pairs) revealed a unique HBV genotype C2
      (HBV/C2) sequence commonly spread in Southeast Asia, which probably represents an
      HBV that infected the Joseon Dynasty population in Korea. Comparison of the aHBV
      sequences with contemporary HBV/C2 DNA sequences revealed distinctive differences
      along four open reading frames. Genetic diversity between contemporary and
      recovered aHBV/C2 DNA may be the result of immunologic, environmental, and/or
      pharmacologic pressures. The calculated time of most recent common ancestor
      suggests that the Korean HBV sequence origin dates back at least 3,000 years and
      possibly as long as 100,000 years. This isolate most likely represents the
      earliest human HBV sequence that colonized Southeast Asia by human migration.
      CONCLUSION: This study describes the complete sequence of the oldest HBV isolate
      and the most ancient full viral genome known so far.

PMID- 22610998
TI  - Inflammatory response of intervertebral disc cells is reduced by fibrin sealant
      scaffold in vitro.
AB  - Intervertebral disc (IVD) degeneration is a complex process characterized by
      elevated concentrations of proinflammatory cytokines and proteolytic enzymes.
      Because of pro-healing constituents, we hypothesized that fibrin sealant (FS) can
      reduce inflammation and augment soft tissue healing within the damaged or
      degenerative IVD. To test this, human and porcine nucleus pulposus (NP) and
      annulus fibrosus (AF) cells were extracted from tissues and encapsulated into
      alginate beads (NP cells) and type I collagen sponges (AF cells). Half of the
      alginate and collagen scaffolds were embedded in FS. To provoke inflammatory
      behaviours, the constructs were cultured with and without continuous IL-1alpha
      (10 ng/ml) for 4, 7 and 14 days. ELISA was used to quantify the cellular
      synthesis (ng/ug DNA) of clinically relevant cytokines, proteolytic enzymes and
      growth factors. In NP cell constructs with IL-1alpha, the syntheses of TNFalpha,
      IL-1beta, IL-6, IL-8 was elevated at all culture durations. In the presence of
      FS, secretion of several pro-inflammatory cytokines were significantly reduced
      [IL-6 and IL-8 (porcine); and TNFalpha, IL-1beta, IL-6, IL-8 (human)]. Consistent
      with these reductions, human NP cultures exposed to FS and FS + IL-1alpha
      synthesized significantly reduced amounts of MMP-1 and -3 compared to constructs
      with IL-1alpha. For porcine and human AF cells, there were no significant
      differences in the synthesis of the inflammatory or proteolytic cytokines
      relative to controls (without IL-1alpha) at any culture duration. However, the
      porcine AF cells exposed to FS synthesized elevated amounts of the anti
      inflammatory cytokine IL-4. The results suggest that FS may have beneficial
      effects for patients with degenerated intervertebral discs.

PMID- 22610997
TI  - Dioxins: diagnostic and prognostic challenges arising from complex mechanisms.
AB  - Dioxins are ubiquitous environmental challenges to humans, with a pervasiveness
      that arises from 200 years of rapid industrialization and mechanization of
      Western societies and which is now extending into the developing world. In spite
      of their penetrance of the human biota, these compounds are poorly understood in
      terms of their true physiological potential for harm, and the mechanisms by which
      they impact cellular and organ level function are only recently becoming clear.
      Emerging awareness that chronic exposures to toxins may have generational and
      subtle effects on the outcomes of diseases such as cancer and diabetes, which are
      already multifactorial and highly complex, creates the context for the current
      review paper. Here, we summarize dioxin exposure paradigms and the resulting
      physiological effects that have been documented in animals and humans. Novel
      insights into potential endogenous end exogenous ligands, as well as the
      mechanisms by which these ligands impact acute and chronic cellular processes,
      are discussed. We develop the idea that the diagnosis of dioxin exposure, the
      subtleties of the cellular effects of the compounds and prognosis of the long
      term effects of exposure are problems requiring that researchers leverage the
      power of genomics and epigenetics. However, the continuation of longitudinal
      epidemiological studies and the development of a firmer basis from which to
      extrapolate animal studies will be critical in ensuring optimal insight from
      these resource-intensive techniques.

PMID- 22611000
TI  - Assessment of bias in experimentally measured diffusion tensor imaging parameters
      using SIMEX.
AB  - Diffusion tensor imaging enables in vivo investigation of tissue cytoarchitecture
      through parameter contrasts sensitive to water diffusion barriers at the
      micrometer level. Parameters are derived through an estimation process that is
      susceptible to noise and artifacts. Estimated parameters (e.g., fractional
      anisotropy) exhibit both variability and bias relative to the true parameter
      value estimated from a hypothetical noise-free acquisition. Herein, we present
      the use of the simulation and extrapolation (SIMEX) approach for post hoc
      assessment of bias in a massively univariate imaging setting and evaluate the
      potential of a SIMEX-based bias correction. Using simulated data with known truth
      models, spatially varying fractional anisotropy bias error maps are evaluated on
      two independent and highly differentiated case studies. The stability of SIMEX
      and its distributional properties are further evaluated on 42 empirical diffusion
      tensor imaging datasets. Using gradient subsampling, an empirical experiment with
      a known true outcome is designed and SIMEX performance is compared to the
      original estimator. With this approach, we find SIMEX bias estimates to be highly
      accurate offering significant reductions in parameter bias for individual
      datasets and greater accuracy in averaged population-based estimates.

PMID- 22610999
TI  - The double-edged sword of goal engagement: consequences of goal pursuit in
      bipolar disorder.
AB  - A series of studies suggest that bipolar disorder is related to high sensitivity
      to incentives and that incentive sensitivity (or sensitivity of the approach
      system) can predict the course of mania. Incentive sensitivity in bipolar
      disorder seems to be related to two processes: a tendency to invest in difficult
      to-attain goals and an over-reactivity to cues of goal progress versus thwarting.
      Both of those processes appear relevant to symptom generation. Hence, bipolar
      disorder seems related to a greater emphasis on reaching goals and also a
      problematic reactivity to reaching those highly desired goals. We suggest
      directions for treatment development focused on these issues in goal regulation.

PMID- 22611001
TI  - Lesion size affects diagnostic performance of IOTA logistic regression models,
      IOTA simple rules and risk of malignancy index in discriminating between benign
      and malignant adnexal masses.
AB  - OBJECTIVES: To estimate the ability to discriminate between benign and malignant
      adnexal masses of different size using: subjective assessment, two International
      Ovarian Tumor Analysis (IOTA) logistic regression models (LR1 and LR2), the IOTA
      simple rules and the risk of malignancy index (RMI). METHODS: We used a
      multicenter IOTA database of 2445 patients with at least one adnexal mass, i.e.
      the database previously used to prospectively validate the diagnostic performance
      of LR1 and LR2. The masses were categorized into three subgroups according to
      their largest diameter: small tumors (diameter < 4 cm; n = 396), medium-sized
      tumors (diameter, 4-9.9 cm; n = 1457) and large tumors (diameter >= 10 cm, n =
      592). Subjective assessment, LR1 and LR2, IOTA simple rules and the RMI were
      applied to each of the three groups. Sensitivity, specificity, positive and
      negative likelihood ratio (LR+, LR-), diagnostic odds ratio (DOR) and area under
      the receiver-operating characteristics curve (AUC) were used to describe
      diagnostic performance. A moving window technique was applied to estimate the
      effect of tumor size as a continuous variable on the AUC. The reference standard
      was the histological diagnosis of the surgically removed adnexal mass. RESULTS:
      The frequency of invasive malignancy was 10% in small tumors, 19% in medium-sized
      tumors and 40% in large tumors; 11% of the large tumors were borderline tumors vs
      3% and 4%, respectively, of the small and medium-sized tumors. The type of benign
      histology also differed among the three subgroups. For all methods, sensitivity
      with regard to malignancy was lowest in small tumors (56-84% vs 67-93% in medium
      sized tumors and 74-95% in large tumors) while specificity was lowest in large
      tumors (60-87%vs 83-95% in medium-sized tumors and 83-96% in small tumors ). The
      DOR and the AUC value were highest in medium-sized tumors and the AUC was largest
      in tumors with a largest diameter of 7-11 cm. CONCLUSION: Tumor size affects the
      performance of subjective assessment, LR1 and LR2, the IOTA simple rules and the
      RMI in discriminating correctly between benign and malignant adnexal masses. The
      likely explanation, at least in part, is the difference in histology among tumors
      of different size.

PMID- 22611002
TI  - Arachidonic acid/docosahexaenoic acid-supplemented diet in early life reduces
      body weight gain, plasma lipids, and adiposity in later life in ApoE*3Leiden
      mice.
AB  - SCOPE: This study addresses whether early life arachidonic acid
      (ARA)/docosahexaenoic acid (DHA) supplementation or eicosapentaenoic acid
      (EPA)/DHA (Omacor) supplementation affects body weight gain, lipid metabolism,
      and adipose tissue quantity and quality in later life in ApoE*3Leiden-transgenic
      mice, a humanized model for hyperlipidemia and mild obesity. METHODS AND RESULTS:
      Four-week-old male ApoE*3Leiden mice were fed chow diet with or without a mixture
      of ARA (0.129 wt%) and DHA (0.088 wt%) or Omacor (0.30 wt% EPA, 0.25 wt% DHA). At
      age 12 weeks, mice were fed high-fat/high-carbohydrate (HFHC) diet without above
      supplements until age 20 weeks. Control mice received chow diet throughout the
      study. Mice receiving ARA/DHA gained less body weight compared to control and
      this effect was sustained when fed HFHC. Omacor had no significant effect on body
      weight gain. Plasma cholesterol and triglycerides were significantly lowered by
      both supplementations. At 20 weeks, epididymal fat mass was less in ARA/DHA
      supplemented mice, while Omacor had no significant effect on fat mass. Both
      ARA/DHA and Omacor reduced inguinal adipocyte cell size; only ARA/DHA
      significantly reduced epididymal macrophage infiltration. CONCLUSION: This study
      shows that early life ARA/DHA, but not Omacor supplementation improves body
      weight gain later in life. ARA/DHA and to a lesser extent Omacor both improved
      adipose tissue quality.

PMID- 22611003
TI  - Live imaging in zebrafish reveals neu(trophil) insight into the metastatic niche.
AB  - Non-cancerous immune cells can significantly contribute to tumour progression and
      metastases. Neutrophils associated with tumours can both promote and inhibit
      tumour progression, but less is known about how non-associated immune cells
      contribute to cancer biology. In a recent issue of the Journal of Pathology, He
      and colleagues use non-invasive, high-resolution imaging of the whole living
      animal to provide a compelling glimpse at how physiological migration of
      neutrophils can prepare a metastatic niche and how their activities can be
      altered by the unintended consequences of targeted therapeutics.

PMID- 22611004
TI  - Dynamic hysteresis between gradient echo and spin echo attenuations in dynamic
      susceptibility contrast imaging.
AB  - Perfusion measurements using dynamic susceptibility contrast imaging provide
      additional information about the mean vessel size of microvasculature when
      supplemented with a dual gradient echo (GE) - spin echo (SE) contrast. Dynamic
      increase in the corresponding transverse relaxation rate constant changes,
      DeltaR2GE and DeltaR2SE , forms a loop on the (Delta R2SE3/2, DeltaR2GE ) plane,
      rather than a reversible line. The shape of the loop and the direction of its
      passage differentiate between healthy brain and pathological tissue, such as
      tumour and ischemic tissue. By considering a tree model of microvasculature, the
      direction of the loop is found to be influenced mainly by the relative arterial
      and venous blood volume, as well as the tracer bolus dispersion. A parameter
      Lambda is proposed to characterize the direction and shape of the loop, which
      might be considered as a novel imaging marker for describing the pathology of
      cerebrovascular network.

PMID- 22611005
TI  - First-trimester combined screening for trisomy 21 with different combinations of
      placental growth factor, free beta-human chorionic gonadotropin and pregnancy
      associated plasma protein-A.
AB  - OBJECTIVE: To examine placental growth factor (PlGF) in euploid and trisomy 21
      pregnancies at 11-13 weeks' gestation and to model the impact on first-trimester
      combined screening. METHODS: PlGF was measured in 509 (409 euploid and 100
      trisomic) fetal serum samples derived from prospective first-trimester combined
      screening for trisomy 21 at 11-13 weeks' gestation. The serum samples were stored
      at -80 degrees C, following the measurement of free beta-human chorionic
      gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A)
      levels, for median time spans of 0.9 and 4.1 years in the euploid and trisomy 21
      pregnancies, respectively. The effect of additional PlGF measurement at the time
      of combined screening was investigated by simulating fetal nuchal translucency
      (NT) measurements and multiples of the median (MoM) values for PAPP-A, free beta
      hCG and PlGF for 20,000 euploid and 20,000 trisomy 21 pregnancies. Patient
      specific combined risks were calculated based on maternal age and fetal NT in
      addition to free beta-hCG, PAPP-A and PlGF, PAPP-A and PlGF or free beta-hCG and
      PlGF, and detection and false-positive rates were calculated. RESULTS: Median
      PlGF-MoM was 1.0 (95% confidence interval (CI), 0.96-1.04) in euploid fetuses and
      significantly lower, at 0.73 (95% CI, 0.70-0.76), in trisomy-21 fetuses (P <
      0.0001). There was no significant dependency between PlGF-MoM and either
      gestational age at the time of blood sampling (r = 0.087, P = 0.392) or sample
      storage time (r = 0.028, P = 0.785). Modeled detection and false-positive rates
      for first-trimester combined screening (based on maternal and gestational age,
      fetal NT and maternal serum biochemistry) without PlGF were 85% and 2.7% for a
      fixed risk cut-off of 1:100. The addition of PlGF increased the detection rate to
      87% and reduced the false-positive rate to 2.6%. Screening by maternal age and
      fetal NT in combination with PlGF and PAPP-A or in combination with PlGF and free
      beta-hCG provided detection rates of 82% and 79%, with false-positive rates of
      2.7% and 3.0%, respectively. CONCLUSION: In pregnancies with trisomy 21 PlGF is
      reduced. The impact on the overall screening performance for trisomy 21 is low
      and does not justify the measurement of PlGF solely for trisomy 21 screening.
      However, as PlGF is measured with the aim of assessing the risk for pre
      eclampsia, further improvement in screening for trisomy 21 can be considered as
      an added benefit.

PMID- 22611006
TI  - Mechanism studies on the superior optical limiting observed in graphene oxide
      covalently functionalized with upconversion NaYF4 :Yb3+/Er3+ nanoparticles.

PMID- 22611007
TI  - A stitch in time saves none: "large caliber venous hemostasis in pediatric
      practice".

PMID- 22611008
TI  - Megakaryocytes promote hepatoepithelial liver cell development in E11.5 mouse
      embryos by cell-to-cell contact and by vascular endothelial growth factor A
      signaling.
AB  - In the mouse embryo, hematopoietic progenitor cells migrate to the fetal liver
      (FL) between gestational days (E) 9.5 and 10.5, where they rapidly expand to form
      the main fetal reservoir of hematopoietic cells. The embryonic megakaryocyte
      progenitors (MKPs) in the E11.5 FL were identified as CD49f(H) CD41(H) (and c
      Kit(D)KDR(+)CD42(+)CD9(++)CD31(+)) cells, expressing several hepato-specific
      proteins. Unlike adult bone marrow megakaryocytes (MKs), embryonic MKPs were
      CD45(-) and represent an abundant population in the FL. The CD49f(H)CD41(H) MKPs
      purified by cytometry differentiated in vitro to produce proplatelets,
      independent of thrombopoietin stimulation, and they responded to stimulation with
      adenosine diphosphate, thrombin, and the PAR4 thrombin receptor-activating
      peptide. Moreover, after removing CD49f(H)CD41(H) MKPs from purified E11.5 FL
      hepatoepithelial-enriched cell preparations (c-Kit(D)CD45(-)Ter119(-)), the
      remaining CD49f(D) cells neither differentiated nor survived in vitro. Indeed,
      direct cell-to-cell contact between the CD49f(H) CD41(H) and CD49f(D) populations
      was required to promote the hepatocyte differentiation of CD49f(D) cells. The
      addition of vascular endothelial growth factor A (VEGF-A) and medium conditioned
      by E11.5 CD49f(H)CD41(H) MKPs produced a partial effect on CD49f(D) cells,
      inducing the formation of hepatoepithelial layers. This effect was abolished by
      anti-VEGF-A antibodies. Together, these findings strongly suggest that
      CD49f(H)CD41(H) MKPs are fundamental to promote FL development, as proposed in
      adult liver regeneration. CONCLUSION: The cells of the MK lineage present in the
      developing mouse embryo liver promote the growth of hepatoepithelial cells in
      vitro through VEGF-A signaling and may play a role in liver development in vivo.

PMID- 22611009
TI  - Thrombolysis in hemiballism: is it a rational choice?

PMID- 22611010
TI  - Scientists seek new ways to prevent cancer: presenters at the American Society of
      Preventive Oncology annual meeting discuss biomarkers and trial design.

PMID- 22611011
TI  - New findings presented on metastatic breast cancer and bilateral oophorectomy.

PMID- 22611013
TI  - Active intrathecal herpes simplex virus type 1 (HSV-1) and human herpesvirus-6
      (HHV-6) infection at onset of multiple sclerosis.

PMID- 22611014
TI  - Three-dimensional growth matrix for human embryonic stem cell-derived neuronal
      cells.
AB  - The future of tissue engineering applications for neuronal cells will require a
      supportive 3D matrix. This particular matrix should be soft, elastic and
      supportive for cell growth. In this study, we characterized the suitability of a
      3D synthetic hydrogel matrix, PuraMatrixTM, as a growth platform for human
      embryonic stem cell (hESC)-derived neural cells. The viability of the cells grown
      on top of, inside and under the hydrogel was monitored. The maturation and
      electrical activity of the neuronal networks inside the hydrogel were further
      characterized. We showed that cells stayed viable on the top of the PuraMatrixTM
      surface and growth of the neural cells and neural processes was good. Further,
      hESC-derived neurons, astrocytes and oligodendrocytes all grew, matured and
      migrated when cultured inside the hydrogel. Importantly, neuronal cells were able
      to form electrically active connections that were verified using microelectrode
      array. Thus, PuraMatrix is a good supportive growth matrix for human neural cells
      and may serve as a matrix for neuronal scaffolds in neural tissue engineering.

PMID- 22611015
TI  - The equivalence of linear Gaussian connectivity techniques.
AB  - The theoretical basis of linear Gaussian connectivity methods for the analysis of
      fMRI data is examined in this article, resulting in a clarification of
      methodological dependencies between techniques. In particular, Granger causality
      connectivity procedures, which describe instantaneous and directed influence
      between sets of voxel timeseries, are shown to be remappings of correlation-based
      metrics. Furthermore, the statistical inference tests applied to pairwise Granger
      causality measures are theoretically shown to be equivalent to inference tests
      applied to correlation-based metrics. These results are demonstrated empirically
      using receiver operating characteristic curves derived from vector autoregressive
      models of various lags, sample size, and noise covariance values. The equivalence
      of linear Granger causality and correlation-based methods, in both metric and
      test statistic, renders linear Granger causality a restatement of traditional
      data-driven methodologies in the context of brain connectivity studies.
      Furthermore, the equivalence highlights the centrality of partial correlation and
      partial variance in linear connectivity analyses and bridges the gap between
      functional and effective connectivity techniques. Consequently, rather than a
      distinction rooted in methodological difference, the dichotomy between functional
      and effective connectivity methods is ultimately a function of model
      configuration realized in choices such as the selection of nodes, the choice to
      model instantaneous and/or directed influence, and the choice to employ many
      bivariate models or a single multivariate model. While these theoretical results
      may be unsurprising to the reader with advanced statistical knowledge, they
      highlight the importance of a clear understanding of the theoretical basis of
      connectivity analysis methods for human brain mapping researchers.

PMID- 22611016
TI  - Usefulness of administration of non-organophosphate cholinesterase inhibitors
      before acute exposure to organophosphates: assessment using paraoxon.
AB  - Reversible acetylcholinesterase (AChE) inhibitors can protect against the lethal
      effects of irreversible organophosphorus AChE inhibitors (OPCs), when
      administered before OPC exposure. We have assessed in vivo the mortality-reducing
      efficacy of a group of known AChE inhibitors, when given in equitoxic dosage
      before exposure to the OPC paraoxon. Protection was quantified in rats by
      determining the relative risk (RR) of death. Best in vivo protection from
      paraoxon-induced mortality was observed after prophylactic administration of
      physostigmine (RR = 0.30) or the oxime K-27 (RR = 0.34); both treatments were
      significantly superior to the pre-treatment with all other tested compounds,
      including the established substance pyridostigmine. Tacrine (RR = 0.67),
      ranitidine (RR = 0.72), pyridostigmine (RR = 0.76), tiapride (RR = 0.80) and 7
      MEOTA (RR = 0.86) also significantly reduced the relative risk of paraoxon
      induced death, but to a lesser degree. Methylene blue, amiloride and
      metoclopramide had an unfavorable effect (RR >= 1), significantly increasing
      mortality. When CNS penetration by prophylactic is undesirable K-27 is a
      promising alternative to pyridostigmine.

PMID- 22611017
TI  - Differential drug class-specific metastatic effects following treatment with a
      panel of angiogenesis inhibitors.
AB  - Inhibiting angiogenesis has become an important therapeutic strategy for cancer
      treatment but, like other current targeted therapies, benefits experienced for
      late-stage cancers can be curtailed by inherent refractoriness or by acquired
      drug resistance, requiring a need for better mechanistic understanding of such
      effects. Numerous preclinical studies have demonstrated that VEGF pathway
      inhibitors suppress primary tumour growth and metastasis. However, it has been
      recently reported that short-term VEGF and VEGFR inhibition can paradoxically
      accelerate tumour invasiveness and metastasis in certain models. Here we
      comprehensively compare the effects of both antibody and small molecule receptor
      tyrosine kinase (RTK) inhibitors targeting the VEGF-VEGFR pathway, using short
      term therapy in various mouse models of metastasis. Our findings demonstrate that
      antibody inhibition of VEGF pathway molecules does not promote metastasis, in
      contrast to selected small molecule RTK inhibitors at elevated-therapeutic drug
      dosages. In particular, a multi-targeted RTK inhibitor, sunitinib, which most
      profoundly potentiated metastasis, also increased lung vascular permeability and
      promoted tumour cell extravasation. Mechanistically, sunitinib, but not anti-VEGF
      treatment, attenuated endothelial barrier function in culture and caused a global
      inhibition of protein tyrosine phosphorylation, including molecules important for
      maintaining endothelial cell-cell junctions. Together these findings indicate
      that, rather than a specific consequence of inhibiting the VEGF signalling
      pathway, pharmacological inhibitors of the VEGF pathway can have dose- and drug
      class-dependent side-effects on the host vasculature. These findings also
      advocate for the continued identification of mechanisms of resistance to anti
      angiogenics and for therapy development to overcome it.

PMID- 22611018
TI  - SAR simulations for high-field MRI: how much detail, effort, and accuracy is
      needed?
AB  - Accurate prediction of specific absorption rate (SAR) for high field MRI is
      necessary to best exploit its potential and guarantee safe operation. To reduce
      the effort (time, complexity) of SAR simulations while maintaining robust
      results, the minimum requirements for the creation (segmentation, labeling) of
      human models and methods to reduce the time for SAR calculations for 7 Tesla MR
      imaging are evaluated. The geometric extent of the model required for realistic
      head-simulations and the number of tissue types sufficient to form a reliable but
      simplified model of the human body are studied. Two models (male and female) of
      the virtual family are analyzed. Additionally, their position within the head
      coil is taken into account. Furthermore, the effects of retuning the coils to
      different load conditions and the influence of a large bore radiofrequency-shield
      have been examined. The calculation time for SAR simulations in the head can be
      reduced by 50% without significant error for smaller model extent and simplified
      tissue structure outside the coil. Likewise, the model generation can be
      accelerated by reducing the number of tissue types. Local SAR can vary up to 14%
      due to position alone. This must be considered and sets a limit for SAR
      prediction accuracy. All these results are comparable between the two body models
      tested.

PMID- 22611019
TI  - Mapping physical interactions within chromatin by proteomic approaches.
AB  - Our ability to study protein-protein interactions has grown by leaps and bounds
      in recent years, enabling numerous large-scale studies to be performed in a
      variety of organisms. Despite this success, some classes of proteins, including
      those bound to chromatin, remain difficult to characterize through proteomic
      approaches. Some of the problems faced by researchers studying chromatin-bound
      proteins include low complex solubility, heterogeneous sample composition, and
      numerous transient interactions, which can be further complicated by the presence
      of DNA itself. To tackle these issues, a number of innovative protocols have been
      developed to better study the various facets of chromatin biology. In this
      review, we will discuss novel approaches to study protein-DNA interactions as
      well as protein complexes affecting chromatin.

PMID- 22611020
TI  - Plasmid vectors for proteomic analyses in Giardia: purification of virulence
      factors and analysis of the proteasome.
AB  - In recent years, proteomics has come of age with the development of efficient
      tools for purification, identification, and characterization of gene products
      predicted by genome projects. The intestinal protozoan Giardia intestinalis can
      be transfected, but there is only a limited set of vectors available, and most of
      them are not user friendly. This work delineates the construction of a suite of
      cassette-based expression vectors for use in Giardia. Expression is provided by
      the strong constitutive ornithine carbamoyltransferase (OCT) promoter, and
      tagging is possible in both N- and C-terminal configurations. Taken together, the
      vectors are capable of providing protein localization and production of
      recombinant proteins, followed by efficient purification by a novel affinity tag
      combination, streptavidin binding peptide-glutathione S-transferase (SBP-GST).
      The option of removing the tags from purified proteins was provided by the
      inclusion of a PreScission protease site. The efficiency and feasibility of
      producing and purifying endogenous recombinant Giardia proteins with the
      developed vectors was demonstrated by the purification of active recombinant
      arginine deiminase (ADI) and OCT from stably transfected trophozoites. Moreover,
      we describe the tagging, purification by StrepTactin affinity chromatography, and
      compositional analysis by mass spectrometry of the G. intestinalis 26S proteasome
      by employing the Strep II-FLAG-tandem affinity purification (SF-TAP) tag. This is
      the first report of efficient production and purification of recombinant proteins
      in and from Giardia, which will allow the study of specific parasite proteins and
      protein complexes.

PMID- 22611021
TI  - The HU protein is important for apicoplast genome maintenance and inheritance in
      Toxoplasma gondii.
AB  - The apicoplast, a chloroplast-like organelle, is an essential cellular component
      of most apicomplexan parasites, including Plasmodium and Toxoplasma. The
      apicoplast maintains its own genome, a 35-kb DNA molecule that largely encodes
      proteins required for organellar transcription and translation. Interference with
      apicoplast genome maintenance and function is a validated target for drug therapy
      for malaria and toxoplasmosis. However, the many proteins required for genome
      maintenance and inheritance remain largely unstudied. Here we genetically
      characterize a nucleus-encoded homolog to the bacterial HU protein in Toxoplasma
      gondii. In bacteria, HU is a DNA-binding structural protein with fundamental
      roles in transcription, replication initiation, and DNA repair.
      Immunofluorescence assays reveal that in T. gondii this protein localizes to the
      apicoplast. We have found that the HU protein from Toxoplasma can successfully
      complement bacterial DeltahupA mutants, supporting a similar function. We were
      able to construct a genetic knockout of HU in Toxoplasma. This Deltahu mutant is
      barely viable and exhibits significant growth retardation. Upon further analysis
      of the mutant phenotype, we find that this mutant has a dramatically reduced
      apicoplast genome copy number and, furthermore, suffers defects in the
      segregation of the apicoplast organelle. Our findings not only show that the HU
      protein is important for Toxoplasma cell biology but also demonstrate the
      importance of the apicoplast genome in the biogenesis of the organelle.

PMID- 22611023
TI  - Perinatal outcome in women treated with progesterone for the prevention of
      preterm birth: a meta-analysis.
AB  - OBJECTIVE: To quantify the effect on perinatal outcome in women treated with
      progesterone for the prevention of preterm birth. METHODS: MEDLINE and SCOPUS
      searches, including references of the retrieved articles and additional automated
      search using the 'search for related articles' PubMed function, were used.
      Randomized controlled trials assigning women at risk for preterm birth to
      progesterone or placebo were included (both singleton and multiple pregnancies).
      Outcomes were neonatal and perinatal death, respiratory distress syndrome (RDS),
      retinopathy, necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH)
      Grade 3-4, sepsis, admission to the neonatal intensive care unit (NICU) and
      composite adverse outcome. RESULTS: Sixteen studies (singletons, n = 7; twins, n
      = 7; triplets, n = 2) were included in the meta-analysis. For singleton
      pregnancies, progesterone reduced the rates of neonatal death (risk ratio (RR)
      0.487 (95% CI, 0.290-0.818)), RDS (RR 0.677 (95% CI, 0.490-0.935)), NICU
      admission (RR 0.410 (95% CI, 0.204-0.823)) and composite adverse outcome (RR
      0.576 (95% CI, 0.373-0.891)). No favorable effect was observed in twins; in fact,
      progesterone was associated with increased rates of perinatal death (RR 1.551
      (95% CI, 1.014-2.372)), RDS (RR 1.218 (95% CI, 1.038-1.428)) and composite
      adverse outcome (RR 1.211 (95% CI, 1.029-1.425)). No significant effect was
      observed in triplet pregnancies. CONCLUSION: Progesterone administration in
      singleton pregnancies at risk for preterm birth improves perinatal outcomes, but
      may actually have adverse effects in multiple pregnancies.

PMID- 22611022
TI  - SPO71 mediates prospore membrane size and maturation in Saccharomyces cerevisiae.
AB  - The mechanisms that control the size and shape of membranes are not well
      understood, despite the importance of these structures in determining organelle
      and cell morphology. The prospore membrane, a double lipid bilayer that is
      synthesized de novo during sporulation in S. cerevisiae, grows to surround the
      four meiotic products. This membrane determines the shape of the newly formed
      spores and serves as the template for spore wall deposition. Ultimately, the
      inner leaflet of the prospore membrane will become the new plasma membrane of the
      cell upon germination. Here we show that Spo71, a pleckstrin homology domain
      protein whose expression is induced during sporulation, is critical for the
      appropriate growth of the prospore membrane. Without SPO71, prospore membranes
      surround the nuclei but are abnormally small, and spore wall deposition is
      disrupted. Sporulating spo71Delta cells have prospore membranes that properly
      localize components to their growing leading edges yet cannot properly localize
      septin structures. We also found that SPO71 genetically interacts with SPO1, a
      gene with homology to the phospholipase B gene that has been previously
      implicated in determining the shape of the prospore membrane. Together, these
      results show that SPO71 plays a critical role in prospore membrane development.

PMID- 22611024
TI  - Interaction between intestinal dendritic cells and bacteria translocated from the
      gut in rats with cirrhosis.
AB  - Cirrhosis with ascites is associated with a high rate of gut bacterial
      translocation (GBT) and spontaneous bacterial infections of enteric origin. We
      addressed the activation state and role of intestinal dendritic cells (DCs) in
      experimental ascitic cirrhosis and their relationship with GBT. Cirrhosis with
      ascites was CCl(4) induced in rats. To examine their activation state and
      functions, DCs (CD103(+) RT1B(+) CD3(-) CD45RA(-) ) were isolated from the
      intestinal lamina propria and mesenteric lymph nodes (MLNs), and the following
      parameters were determined by flow cytometry: surface antigen expression;
      spontaneous or lipopolysaccharide-stimulated tumor necrosis factor alpha (TNF
      alpha) production; and in vitro capacity to phagocytose latex beads and to
      migrate toward the chemokine (C-C motif) ligand 21. GBT was defined as the growth
      of bacteria in MLNs culture. Bacterial DNA (Bact-DNA) in MLNs was identified by
      polymerase chain reaction. In rats with Bact-DNA in MLNs without GBT, intestinal
      and MLNs CD103(+) -DCs showed features of activation, expansion of the
      proinflammatory CD4(+) -DC subpopulation, augmented TNF-alpha production, and
      increased phagocytic and migratory capacities. In contrast, in rats with GBT,
      CD103(+) -DCs showed the absence of an activated phenotype, lowered TNF-alpha
      production, and relatively deficient phagocytosis and migration capacities. The
      CD103(+) -DC of rats without Bact-DNA in MLNs or GBT were similar to controls. In
      cirrhotic rats, bowel decontamination with antibiotics eliminated Bact-DNA in
      MLNs and GBT, normalized the activation state and functions of CD103(+) -DCs, and
      increased their TNF-alpha production. CONCLUSION: In experimental cirrhosis with
      ascites, continuous pressure of gut bacteria shapes the phenotypic and functional
      profile of intestinal DCs to produce effects that range from their activation and
      enhanced functions to their exhaustion and tolerance.

PMID- 22611025
TI  - Early changes in cerebral oxidative stress and apoptotic neuronal injury after
      various flows for selective cerebral perfusion in piglets.
AB  - BACKGROUND: The impact of various flows for selective cerebral perfusion (SCP) on
      cerebral oxidative stress in the immature brain is unknown. We examined early
      changes in cerebral markers of oxidative damage, apoptotic protein activation and
      histological outcome after different flows for SCP in a piglet model of deep
      hypothermic circulatory arrest (DHCA). METHODS: Twenty piglets, randomly divided
      into four groups (each n = 5), were placed on cardiopulmonary bypass (CPB) at 20
      degrees C, then underwent DHCA for 60 minutes. SCP was conducted at flow rates of
      0, 25, 50 and 80 ml.kg(-1).min(-1) through the innominate artery in the DHCA, SCP
      25, SCP 50, and SCP 80 groups, respectively. The animals were killed at 2 hours
      off CPB. Brain tissues were examined for the activity of SOD, MDA and caspase-3,
      and histological damage was quantitatively assayed by light microscopic
      examinations. RESULTS: There were no significant differences in the activities of
      SOD, MDA and the SOD/MDA index between the groups. Caspase-3 activity
      significantly decreased in the SCP 25, SCP 50 and SCP 80 groups compared with the
      DHCA group. However, the caspase-3 level was higher in the SCP 80 group than in
      the SCP 25 and SCP 50 group. There were no significant correlations between MDA,
      SOD, SOD/MDA index and caspase-3. CONCLUSIONS: In this acute model, under
      different flows for SCP, cerebral MDA and SOD activities show no change, whereas
      activated caspase-3 has a marked change. There was no relationship between
      oxidative stress, indicated by MDA and SOD, and apoptotic protein activation in
      the early phase after DHCA.

PMID- 22611026
TI  - Evolution of cerebral perfusion techniques in type a aortic dissection surgery: a
      single center experience.
AB  - BACKGROUND: The purpose of this study was to investigate the effect of using
      antegrade selective cerebral perfusion (ASCP) with moderate hypothermia on
      hospital mortality after surgery for acute type A aortic dissection (AAAD).
      METHODS: Between January 1998 and December 2008, 142 consecutive patients were
      operated on for AAAD. Patients were divided into two subgroups: the cohort of
      patients operated on from January 1998 until December 2003 (without ASCP) (P1998
      2003, n=64) and the cohort operated on from January 2004 until December 2008
      (with ASCP)(P2004-2008, n=78). RESULTS: The difference in hospital mortality was
      statistically significant (P1998-2003: 42.2%; P2004-2008: 14.1%, p<0.0005).
      Survival rates were 51.6+/-6.2% vs. 75.1+/-5.5% and 45.9+/-6.2% vs. 69.7+/-7.3%
      for one and four years, respectively (p=0.001). Multivariate logistic regression
      analysis revealed that ASCP was the only independent protective factor of
      hospital mortality (p=0.047). CONCLUSION: In patients operated on for AAAD,
      antegrade selective cerebral perfusion with moderate hypothermia is a significant
      factor in decreasing hospital mortality.

PMID- 22611027
TI  - Vandetanib, an inhibitor of VEGF receptor-2 and EGF receptor, suppresses tumor
      development and improves prognosis of liver cancer in mice.
AB  - PURPOSE: VEGF, EGF, and TGF-alpha are expressed in hepatocellular carcinomas
      (HCC) and play a role in its growth. Vandetanib, a multikinase inhibitor,
      suppresses the phosphorylation of VEGF receptor 2 (VEGFR-2) and EGF receptor
      (EGFR). The aim of this study was to clarify the antitumor effect of vandetanib
      in mouse HCCs. EXPERIMENTAL DESIGN: We evaluated the effects of vandetanib on
      proliferation of human umbilical vein endothelial cells (HUVEC) and three
      hepatoma cell lines, as well as the phosphorylation of VEGFR-2 and EGFR in these
      cells. Mice were implanted with hepatoma cells subcutaneously or orthotopically
      in the liver and treated with 50 or 75 mg/kg vandetanib. We analyzed the effects
      of treatment on tumor cell proliferation and apoptosis, vessel density,
      phosphorylation of VEGFR-2 and EGFR, and production of VEGF, TGF-alpha, and EGF
      in tumor tissues. Adverse events on vandetanib administration were also
      investigated. RESULTS: Vandetanib suppressed phosphorylation of VEGFR-2 in HUVECs
      and EGFR in hepatoma cells and inhibited cell proliferation. In tumor-bearing
      mice, vandetanib suppressed phosphorylation of VEGFR-2 and EGFR in tumor tissues,
      significantly reduced tumor vessel density, enhanced tumor cell apoptosis,
      suppressed tumor growth, improved survival, reduced number of intrahepatic
      metastases, and upregulated VEGF, TGF-alpha, and EGF in tumor tissues. Treatment
      with vandetanib was not associated with serious adverse events, including alanine
      aminotransferase abnormality, bone marrow suppression, or body weight loss.
      CONCLUSIONS: The antitumor effects of vandetanib in mice suggest that it is a
      potentially suitable and safe chemotherapeutic agent for HCCs.

PMID- 22611029
TI  - Introduction to the special issue on neural stem cells: regulation and function.

PMID- 22611028
TI  - Brachyury, a driver of the epithelial-mesenchymal transition, is overexpressed in
      human lung tumors: an opportunity for novel interventions against lung cancer.
AB  - PURPOSE: The epithelial-mesenchymal transition (EMT) is emerging as a critical
      factor for the progression and metastasis of carcinomas, as well as drug
      resistance. The T-box transcription factor Brachyury has been recently
      characterized as a driver of EMT in human carcinoma cells. The purpose of this
      study was to characterize Brachyury as a potential target for lung cancer
      therapy. EXPERIMENTAL DESIGN: The expression of Brachyury was evaluated by PCR
      and by immunohistochemistry in human lung tumors and adult normal tissues.
      Brachyury gene copy number and promoter methylation status were analyzed in tumor
      tissues with various levels of Brachyury expression. Lung carcinoma cells'
      susceptibility to T-cell lysis and EGF receptor (EGFR) kinase inhibition were
      also evaluated relative to the levels of Brachyury. RESULTS: Our results showed
      Brachyury protein expression in 41% of primary lung carcinomas, including 48% of
      adenocarcinomas and 25% of squamous cell carcinomas. With the exception of normal
      testis and some thyroid tissues, the majority of normal tissues evaluated in this
      study were negative for the expression of Brachyury protein. Brachyury-specific T
      cells could lyse Brachyury-positive tumors and the level of Brachyury
      corresponded to resistance of tumor cells to EGFR kinase inhibition. CONCLUSION:
      We hypothesize that the elimination of Brachyury-positive tumor cells may be able
      to prevent and/or diminish tumor dissemination and the establishment of
      metastases. The ability of Brachyury-specific T-cell lines to lyse Brachyury
      positive tumor cells, in vitro, supports the development of Brachyury-based
      immunotherapeutic approaches for the treatment of lung cancer.

PMID- 22611030
TI  - Performing label-fusion-based segmentation using multiple automatically generated
      templates.
AB  - Classically, model-based segmentation procedures match magnetic resonance imaging
      (MRI) volumes to an expertly labeled atlas using nonlinear registration. The
      accuracy of these techniques are limited due to atlas biases, misregistration,
      and resampling error. Multi-atlas-based approaches are used as a remedy and
      involve matching each subject to a number of manually labeled templates. This
      approach yields numerous independent segmentations that are fused using a voxel
      by-voxel label-voting procedure. In this article, we demonstrate how the multi
      atlas approach can be extended to work with input atlases that are unique and
      extremely time consuming to construct by generating a library of multiple
      automatically generated templates of different brains (MAGeT Brain). We
      demonstrate the efficacy of our method for the mouse and human using two
      different nonlinear registration algorithms (ANIMAL and ANTs). The input atlases
      consist a high-resolution mouse brain atlas and an atlas of the human basal
      ganglia and thalamus derived from serial histological data. MAGeT Brain
      segmentation improves the identification of the mouse anterior commissure (mean
      Dice Kappa values (kappa = 0.801), but may be encountering a ceiling effect for
      hippocampal segmentations. Applying MAGeT Brain to human subcortical structures
      improves segmentation accuracy for all structures compared to regular model-based
      techniques (kappa = 0.845, 0.752, and 0.861 for the striatum, globus pallidus,
      and thalamus, respectively). Experiments performed with three manually derived
      input templates suggest that MAGeT Brain can approach or exceed the accuracy of
      multi-atlas label-fusion segmentation (kappa = 0.894, 0.815, and 0.895 for the
      striatum, globus pallidus, and thalamus, respectively).

PMID- 22611031
TI  - Estimated clinical benefit of protecting neurogenesis in the developing brain
      during radiation therapy for pediatric medulloblastoma.
AB  - We sought to assess the feasibility and estimate the benefit of sparing the
      neurogenic niches when irradiating the brain of pediatric patients with
      medulloblastoma (MB) based on clinical outcome data. Pediatric MB survivors
      experience a high risk of neurocognitive adverse effects, often attributed to the
      whole-brain irradiation that is part of standard management. Neurogenesis is very
      sensitive to radiation, and limiting the radiation dose to the hippocampus and
      the subventricular zone (SVZ) may preserve neurocognitive function. Radiotherapy
      plans were created using 4 techniques: standard opposing fields, intensity
      modulated radiotherapy (IMRT), intensity-modulated arc therapy (IMAT), and
      intensity-modulated proton therapy (IMPT). Mean dose to the hippocampus and SVZ
      (mean for both sites) could be limited to 88.3% (range, 83.6%-91.0%), 77.1%
      (range, 71.5%-81.3%), and 42.3% (range, 26.6%-51.2%) with IMAT, IMRT, and IMPT,
      respectively, while maintaining at least 95% of the prescribed dose in 95% of the
      whole-brain target volume. Estimated risks for developing memory impairment after
      a prescribed dose of 23.4 Gy were 47% (95% confidence interval [CI], 21%-69%),
      44% (95% CI, 21%-65%), 41% (95% CI, 22%-60%), and 33% (95% CI, 23%-44%) with
      opposing fields, IMAT, IMRT, and IMPT, respectively. Neurogenic niche sparing
      during cranial irradiation of pediatric patients with MB is feasible and is
      estimated to lower the risks of long-term neurocognitive sequelae. Greatest
      sparing is achieved with intensity-modulated proton therapy, thus making this an
      attractive option to be tested in a prospective clinical trial.

PMID- 22611032
TI  - Importance of interaction between nerve growth factor and alpha9beta1 integrin in
      glial tumor angiogenesis.
AB  - NGF is a growth factor for which the role in the promotion of angiogenesis is
      still not completely understood. We found that NGF promotes the pathological
      neovascularization process in glioma through a direct interaction with
      alpha9beta1 integrin, which is up-regulated on microvascular endothelial cells in
      cancer tissue. We propagated gHMVEC primary cells using a new method of immune
      selection, and these cells demonstrated alpha9beta1 integrin-dependent binding of
      NGF in a cell adhesion assay. Moreover, NGF induced gHMVEC proliferation and
      chemotaxis inhibited by specific blockers of alpha9beta1 integrin, such as MLD
      disintegrins and monoclonal antibody Y9A2. A Matrigel tube formation assay
      revealed that NGF significantly increased capillary-like growth from gHMVEC to a
      level comparable to treatment with VEGF. The snake venom disintegrin, VLO5,
      inhibited the agonistic effect of both growth factors, whereas the effect of Y9A2
      was not statistically significant. Angiogenesis exogenously induced by NGF  was
      also alpha9beta1-integrin dependent in an embryonic quail CAM system. However,
      angiogenesis pathologically induced by developing glioma in this system was only
      sensitive for inhibition with MLD-disintegrin, suggesting a more complex effect
      of cancer cells on the neovascularization process. The anti-angiogenic effect of
      MLD-disintegrins is probably related to their pro-apoptotic ability induced in
      activated tumoral endothelial cells. Therefore, the molecular basis of these
      disintegrins may be useful for developing new angiostatic pharmaceuticals for
      application in cancer therapy.

PMID- 22611033
TI  - Transient alterations of the blood-brain barrier tight junction and receptor
      potential channel gene expression by chlorpyrifos.
AB  - The blood-brain barrier (BBB) is formed by specialized endothelial cells lining
      capillaries in the central nervous system (CNS). We previously demonstrated that
      exposure to very low concentrations of the organophosphorus insecticide
      chlorpyrifos (CPF) decreased electrical resistance across the BBB in vitro,
      indicating a loss of BBB integrity. The present study examined the transient
      effects of CPF on expression of genes contributing to tight junctions of the BBB.
      Rat brain endothelial cells (RBE4) were co-cultured with rat astrocytes on
      membrane inserts to form an in vitro BBB. The RBE4 cells in the BBB were then
      exposed to CPF for 2, 4 and 12 h. Total RNA was extracted from RBE4 cells and
      quantitative real-time PCR (qRT-PCR) was used to quantify levels of gene
      expression of tight junction proteins claudin5, scaffold proteins zona occludens
      (ZO1) and transient receptor potential (canonical) channels (TRPC4). Gene
      expression decreased 2 h after exposure to CPF, especially TRPC4, but the effects
      were reversed 12 h later. CPF exposure for only 15 min caused less effect than
      longer exposures, with TRPC4 gene expression above the control at 4 h. These
      results suggest that altering gene expression for claudin5, TRPC4 and ZO1 by CPF
      may directly contribute to BBB disruption, and that the alteration is reversible
      upon removal of CPF.

PMID- 22611035
TI  - Investigating the prevalence of complex fiber configurations in white matter
      tissue with diffusion magnetic resonance imaging.
AB  - It has long been recognized that the diffusion tensor model is inappropriate to
      characterize complex fiber architecture, causing tensor-derived measures such as
      the primary eigenvector and fractional anisotropy to be unreliable or misleading
      in these regions. There is however still debate about the impact of this problem
      in practice. A recent study using a Bayesian automatic relevance detection (ARD)
      multicompartment model suggested that a third of white matter (WM) voxels contain
      crossing fibers, a value that, whilst already significant, is likely to be an
      underestimate. The aim of this study is to provide more robust estimates of the
      proportion of affected voxels, the number of fiber orientations within each WM
      voxel, and the impact on tensor-derived analyses, using large, high-quality
      diffusion-weighted data sets, with reconstruction parameters optimized
      specifically for this task. Two reconstruction algorithms were used: constrained
      spherical deconvolution (CSD), and the ARD method used in the previous study. We
      estimate the proportion of WM voxels containing crossing fibers to be ~90% (using
      CSD) and 63% (using ARD). Both these values are much higher than previously
      reported, strongly suggesting that the diffusion tensor model is inadequate in
      the vast majority of WM regions. This has serious implications for downstream
      processing applications that depend on this model, particularly tractography, and
      the interpretation of anisotropy and radial/axial diffusivity measures.

PMID- 22611034
TI  - Solution structure and small angle scattering analysis of TraI (381-569).
AB  - TraI, the F plasmid-encoded nickase, is a 1756 amino acid protein essential for
      conjugative transfer of plasmid DNA from one bacterium to another. Although
      crystal structures of N- and C-terminal domains of F TraI have been determined,
      central domains of the protein are structurally unexplored. The central region
      (between residues 306 and 1520) is known to both bind single-stranded DNA (ssDNA)
      and unwind DNA through a highly processive helicase activity. Here, we show that
      the ssDNA binding site is located between residues 381 and 858, and we also
      present the high-resolution solution structure of the N-terminus of this region
      (residues 381-569). This fragment folds into a four-strand parallel beta sheet
      surrounded by alpha helices, and it resembles the structure of the N-terminus of
      helicases such as RecD and RecQ despite little sequence similarity. The structure
      supports the model that F TraI resulted from duplication of a RecD-like domain
      and subsequent specialization of domains into the more N-terminal ssDNA binding
      domain and the more C-terminal domain containing helicase motifs. In addition, we
      provide evidence that the nickase and ssDNA binding domains of TraI are held
      close together by an 80-residue linker sequence that connects the two domains.
      These results suggest a possible physical explanation for the apparent negative
      cooperativity between the nickase and ssDNA binding domain.

PMID- 22611036
TI  - Anti-VEGF antibody therapy does not promote metastasis in genetically engineered
      mouse tumour models.
AB  - Resistance to anti-angiogenic therapy can occur via several potential mechanisms.
      Unexpectedly, recent studies showed that short-term inhibition of either VEGF or
      VEGFR enhanced tumour invasiveness and metastatic spread in preclinical models.
      In an effort to evaluate the translational relevance of these findings, we
      examined the consequences of long-term anti-VEGF monoclonal antibody therapy in
      several well-validated genetically engineered mouse tumour models of either
      neuroendocrine or epithelial origin. Anti-VEGF therapy decreased tumour burden
      and increased overall survival, either as a single agent or in combination with
      chemotherapy, in all four models examined. Importantly, neither short- nor long
      term exposure to anti-VEGF therapy altered the incidence of metastasis in any of
      these autochthonous models, consistent with retrospective analyses of clinical
      trials. In contrast, we observed that sunitinib treatment recapitulated
      previously reported effects on tumour invasiveness and metastasis in a pancreatic
      neuroendocrine tumour (PNET) model. Consistent with these results, sunitinib
      treatment resulted in an up-regulation of the hypoxia marker GLUT1 in PNETs,
      whereas anti-VEGF did not. These results indicate that anti-VEGF mediates anti
      tumour effects and therapeutic benefits without a paradoxical increase in
      metastasis. Moreover, these data underscore the concept that drugs targeting VEGF
      ligands and receptors may affect tumour metastasis in a context-dependent manner
      and are mechanistically distinct from one another.

PMID- 22611038
TI  - Modulation of aryl hydrocarbon receptor-regulated genes by acute administration
      of ammonium metavanadate in kidney, lung and heart of C57BL/6 mice.
AB  - We recently reported that vanadium (V(5+) ) was able to decrease the 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD)-mediated induction of Cyp1a1 and Nqo1 at mRNA,
      protein and catalytic activity levels in mouse hepatoma Hepa 1c1c7 and human
      hepatoma HepG2 cells. However, little is known regarding the in vivo effects.
      Thus, the objective of this study was to investigate whether similar effects
      would occur at the in vivo level. Therefore, we examined the effect of exposure
      to V(5+) (5 mg kg(-1) ) with or without TCDD (15 ug kg(-1) ) on the AhR-regulated
      genes in kidney, lung and heart of C57BL/6 J mice. Our results demonstrated that
      V(5+) alone significantly decreased Cyp1b1 protein and catalytic activity levels
      in kidney at 24 h. Moreover, it significantly potentiated Nqo1 and Gsta1 gene
      expression in the heart, and only Gsta1 gene expression in the lung. Upon co
      exposure, we found that V(5+) significantly inhibited the TCDD-mediated induction
      of Cyp1a1, Cyp1a2 and Cyp1b1 mRNA, protein and catalytic activity levels in the
      kidney at 24 h. On the other hand, V(5+) significantly potentiated the TCDD
      mediated induction of Nqo1 and Gsta1 protein and activity levels in the kidney.
      Cyp1a1, Cyp1b1, Nqo1 mRNA, protein and catalytic activity levels in the lung were
      significantly potentiated at 6 h. Interestingly, all tested genes in the heart
      were significantly decreased at 6 h with the exception of Gsta1 mRNA. The present
      study demonstrates that V(5+) modulates TCDD-induced AhR-regulated genes.
      Furthermore, the effect on one of these enzymes could not be generalized to other
      enzymes even if it was in the same organ.

PMID- 22611039
TI  - False-positive phencyclidine immunoassay results caused by 3,4
      methylenedioxypyrovalerone (MDPV).

PMID- 22611040
TI  - Patients transplanted for nonalcoholic steatohepatitis are at increased risk for
      postoperative cardiovascular events.
AB  - Nonalcoholic steatohepatitis (NASH) is an independent predictor of coronary
      artery disease (CAD). Our aim was to compare the incidence of cardiovascular (CV)
      events between patients transplanted for NASH and alcohol (ETOH)-induced
      cirrhosis. This is a retrospective cohort study (August 1993 to March 2010) of
      242 patients (115 NASH and 127 ETOH) with >=12 months follow-up after liver
      transplantation (LT). Those with hepatocellular carcinoma or coexisting liver
      diseases were excluded. Kaplan-Meier's and Cox's proportional hazard analyses
      were conducted to compare survival. Logistic regression was used to calculate the
      likelihood of CV events, defined as death from any cardiac cause, myocardial
      infarction, acute heart failure, cardiac arrest, arrhythmia, complete heart
      block, and/or stroke requiring hospitalization <1 year after LT. Patients in the
      NASH group were older (58.4 versus 53.3 years) and were more likely to be female
      (45% versus 18%; P < 0.001). They were more likely to be morbidly obese (32%
      versus 9%), have dyslipidemia (25% versus 6%), or have hypertension (53% versus
      38%; P < 0.01). On multivariate analysis, NASH patients were more likely to have
      a CV event <1 year after LT, compared to ETOH patients, even after controlling
      for recipient age, sex, smoking status, pretransplant diabetes, CV disease, and
      the presence of metabolic syndrome (26% versus 8%; odds ratio = 4.12; 95%
      confidence interval = 1.91-8.90). The majority (70%) of events occurred in the
      perioperative period, and the occurrence of a CV event was associated with a 50%
      overall mortality. However, there were no differences in patient, graft, or CV
      mortality between groups. CONCLUSIONS: CV complications are common after LT, and
      NASH patients are at increased risk independent of traditional cardiac risk
      factors, though this did not affect overall mortality.

PMID- 22611037
TI  - Integrating mass spectrometry of intact protein complexes into structural
      proteomics.
AB  - MS analysis of intact protein complexes has emerged as an established technology
      for assessing the composition and connectivity within dynamic, heterogeneous
      multiprotein complexes at low concentrations and in the context of mixtures. As
      this technology continues to move forward, one of the main challenges is to
      integrate the information content of such intact protein complex measurements
      with other MS approaches in structural biology. Methods such as H/D exchange,
      oxidative foot-printing, chemical cross-linking, affinity purification, and ion
      mobility separation add complementary information that allows access to every
      level of protein structure and organization. Here, we survey the structural
      information that can be retrieved by such experiments, demonstrate the
      applicability of integrative MS approaches in structural proteomics, and look to
      the future to explore upcoming innovations in this rapidly advancing area.

PMID- 22611041
TI  - Mechanical flutter stimulation induces a lasting response in the sensorimotor
      cortex as revealed with BOLD fMRI.
AB  - It has been recently shown that 20 min of mechanical flutter stimulation induces
      lasting motor cortical excitability changes, as assessed by transcranial magnetic
      stimulation in relaxed hand muscles. The present functional magnetic resonance
      imaging (fMRI) study aims to examine if such neuromodulatory changes are
      reflected in the BOLD signal during a motor test. Therefore, two groups were
      recruited: one group receiving whole-hand flutter stimulation with a frequency of
      25 Hz (FSTIM group, n = 22) and a second group receiving no stimulation (NOSTIM
      group, n = 22). As motor test finger-to-thumb tapping was performed to activate a
      wide sensorimotor network during the fMRI measurements. Three fMRI measurements
      were obtained with this test: before stimulation (PRE), after stimulation
      (POST1), and 1 h after stimulation (POST2). Three regions of interest (ROIs) were
      defined: primary motor area (M1), primary somatosensory area (S1), and
      supplementary motor area. In the absence of baseline differences between both
      groups, the FSTIM group showed increased movement-related brain activations
      compared with the NOSTIM group, both at POST1 and POST2. ROI analysis revealed
      increased blood-oxygenation-level-dependent (BOLD) responses within contralateral
      S1 (+20%) and M1 (+25%) at POST1, which lasted until POST2. These poststimulatory
      effects within S1 and M1 obviously reflect neuroplastic changes associated with
      augmented cortical excitability. These findings are of high clinical relevance,
      for example, to improve the treatment of stroke patients.

PMID- 22611042
TI  - Stereoselective evasion of P-glycoprotein, cytochrome P450 3A, and hydrolases by
      peptide prodrug modification of saquinavir.
AB  - In an approach to overcome biological barriers mediated by P-glycoprotein (P-gp)
      and cytochrome P450 3A (CYP3A), a series of stereoisomeric valine-valine prodrugs
      of saquinavir (SQV) were synthesized and investigated with respect to affinity
      for efflux pump P-gp, and resistance to oxidative and hydrolytic enzymes.
      Cellular uptake and bidirectional transport in Caco-2 cells indicated that all
      peptide SQV conjugates can bypass P-gp-mediated efflux significantly, regardless
      of stereochemistry in promoieties. In comparison with D-configuration, L
      configuration was favored for the interaction between prodrugs and rat hepatic
      CYP3A enzymes, and resulted in a relatively rapid clearance by CYP3A. Elimination
      half-life of SQV in rat liver microsomes was prolonged dramatically by sevenfold
      to 40-fold because of the prodrug modification with the rank order of D-valine-D
      valine-SQV > D-valine-L-valine-SQV > L-valine-D-valine-SQV > L-valine-L-valine
      SQV > D-valine-SQV > L-valine-SQV > SQV. Results of hydrolysis studies performed
      in rat intestinal homogenates and plasma indicated that prodrugs attached with D
      valine exhibited significantly reduced biodegradation. In conclusion, the
      enhanced transepithelial accumulation and enzymatic stability observed by SQV
      peptide prodrug modification are found to be stereoselective. Specific
      stereoisomeric dipeptide prodrugs with optimized metabolic stability can be
      employed to improve oral bioavailability of SQV.

PMID- 22611044
TI  - In vivo protective effect of Copaifera langsdorffii hydroalcoholic extract on
      micronuclei induction by doxorubicin.
AB  - Copaifera lansdorffii Desf. is known as 'copaiba', 'copaiva' or 'pau-de-oleo',
      and is found in part of Brazil. The present study was undertaken to evaluate the
      genotoxic potential of C. langsdorffii leaf hydroalcoholic extract (CLE) and its
      influence on the genotoxicity induced by the chemotherapeutic agent doxorubicin
      (DXR) using the Swiss mouse peripheral blood micronucleus test. HPLC analysis of
      CLE using two monolithic columns linked in series allowed quantification of two
      major flavonoid heterosides, quercitrin and afzelin. Animals were treated with
      CLE by gavage at doses of 10, 20, 40 and 80 mg kg(-1) body weight per day, each
      for 20 days. Peripheral blood samples were collected at 24 and 48 h, and 7, 15
      and 21 days after the beginning of the treatment. For the antigenotoxicity
      evaluation, the animals treated with different concentrations of CLE received DXR
      (15 mg kg(-1) body weight, intraperitoneal) at day 20. The peripheral blood
      samples were collected 24 and 48 h after the treatment with DXR. The results
      demonstrated that CLE itself was not genotoxic in the mouse micronucleus assay.
      In animals treated with CLE and DXR, the number of micronucleus was significantly
      decreased compared with animals receiving DXR alone. The putative antioxidant
      activity of one or more of the active compounds of CLE may explain the effect of
      this plant on DXR genotoxicity.

PMID- 22611045
TI  - Implementation of a patient selection protocol for intra-arterial therapy
      increases treatment rates in patients with acute ischemic stroke.
AB  - BACKGROUND: Strategies for patient selection for intra-arterial therapy (IAT) in
      acute ischemic stroke (AIS) are highly variable. The degree of protocol adoption
      and treatment rates associated with implementation of a service-wide patient
      selection IAT protocol were assessed. METHODS: All patients with AIS
      prospectively recorded in our stroke database from January 2007 to June 2009 were
      reviewed. The IAT patient selection protocol was implemented in March 2008.
      Patients were defined as likely to benefit (LTB) from IAT if they had brain
      imaging completed within 6 h from last known well time, NIH Stroke Scale score >=
      8, infarct volume <= 100 ml and evidence of proximal artery occlusion. RESULTS:
      Of 1348 subjects identified, 118 (8.7%) met the criteria for LTB and 62 (52%)
      underwent IAT. There was a significant increase in rates of IAT among LTB
      patients after protocol implementation (61% vs 40%, p<0.02). In LTB patients,
      factors associated with IAT were stroke duration (OR 0.78, 95% CI 0.6 to 0.9 per
      hour), arrival within later calendar months during study period (OR 1.1, 95% CI
      1.02 to 1.2 per month), intravenous tissue plasminogen activator (OR 0.6, 95% CI
      0.4 to 0.9) and age (OR 0.98, 95% CI 0.95 to 1.02 per year). After multivariable
      adjustment, only stroke duration (OR 0.65, 95% CI 0.5 to 0.8 per hour) remained
      an independent predictor of IAT. CONCLUSIONS: Most patients with AIS did not meet
      our criteria for LTB and only 52% of those defined as LTB received IAT. Protocol
      adoption increased the use of IAT over time; however, further exploration of
      factors associated with the reasons for non-treatment and the impact of IAT on
      outcomes is necessary.

PMID- 22611043
TI  - Computational and informatics strategies for identification of specific protein
      interaction partners in affinity purification mass spectrometry experiments.
AB  - Analysis of protein interaction networks and protein complexes using affinity
      purification and mass spectrometry (AP/MS) is among most commonly used and
      successful applications of proteomics technologies. One of the foremost
      challenges of AP/MS data is a large number of false-positive protein interactions
      present in unfiltered data sets. Here we review computational and informatics
      strategies for detecting specific protein interaction partners in AP/MS
      experiments, with a focus on incomplete (as opposite to genome wide) interactome
      mapping studies. These strategies range from standard statistical approaches, to
      empirical scoring schemes optimized for a particular type of data, to advanced
      computational frameworks. The common denominator among these methods is the use
      of label-free quantitative information such as spectral counts or integrated
      peptide intensities that can be extracted from AP/MS data. We also discuss
      related issues such as combining multiple biological or technical replicates, and
      dealing with data generated using different tagging strategies. Computational
      approaches for benchmarking of scoring methods are discussed, and the need for
      generation of reference AP/MS data sets is highlighted. Finally, we discuss the
      possibility of more extended modeling of experimental AP/MS data, including
      integration with external information such as protein interaction predictions
      based on functional genomics data.

PMID- 22611046
TI  - Thrombo-embolism and antithrombotic therapy for heart failure in sinus rhythm. A
      joint consensus document from the ESC Heart Failure Association and the ESC
      Working Group on Thrombosis.
AB  - Chronic heart failure (HF) with either reduced or preserved ejection fraction is
      common and remains an extremely serious disorder with a high mortality and
      morbidity. Many complications related to HF can be related to thrombosis.
      Epidemiological and pathophysiological data also link HF to an increased risk of
      thrombosis, leading to the clinical consequences of sudden death, stroke,
      systemic thrombo-embolism, and/or venous thrombo-embolism. This consensus
      document of the Heart Failure Association (EHFA) of the European Society of
      Cardiology (ESC) and the ESC Working Group on Thrombosis reviews the published
      evidence and summarizes 'best practice', and puts forward consensus statements
      that may help to define evidence gaps and assist management decisions in everyday
      clinical practice. In HF patients with atrial fibrillation, oral anticoagulation
      is recommended, and the CHA(2)DS(2)-VASc and HAS-BLED scores should be used to
      determine the likely risk-benefit ratio (thrombo-embolism prevention vs. risk of
      bleeding) of oral anticoagulation. In HF patients with reduced left ventricular
      ejection fraction who are in sinus rhythm there is no evidence of an overall
      benefit of vitamin K antagonists (e.g. warfarin) on mortality, with risk of major
      bleeding. Despite the potential for a reduction in ischaemic stroke, there is
      currently no compelling reason to use warfarin routinely for these patients. Risk
      factors associated with increased risk of thrombo-embolic events should be
      identified and decisions regarding use of anticoagulation individualized. Patient
      values and preferences are important determinants when balancing the risk of
      thrombo-embolism against bleeding risk. New oral anticoagulants that offer a
      different risk-benefit profile compared with warfarin may appear as an attractive
      therapeutic option, but this would need to be confirmed in clinical trials.

PMID- 22611047
TI  - Eplerenone and new-onset diabetes in patients with mild heart failure: results
      from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart
      Failure (EMPHASIS-HF).
AB  - AIMS: No studies have examined the effect of mineralocorticoid receptor
      antagonist therapy on new-onset diabetes. In addition, though the combination of
      diabetes and chronic heart failure (CHF) carries a poor prognosis, few studies
      have examined predictors of new-onset diabetes in those with CHF. METHODS AND
      RESULTS: In patients with symptomatically mild CHF who participated in the
      placebo-controlled Eplerenone in Mild Patients Hospitalization and Survival Study
      in Heart Failure, we examined the effect of the aldosterone antagonist,
      eplerenone, on physician-diagnosed diabetes using univariate Cox proportional
      hazard analysis. To identify predictors of new-onset diabetes (measures of
      glycaemia were not available), data from trial arms were combined and
      multivariate Cox proportional hazard analyses and receiver operating
      characteristic curve analyses were conducted. At baseline, the mean age of 1846
      initially non-diabetic patients was 69 years and mean left ventricular ejection
      fraction was 26%. Over 21 months, 69 (3.7%) developed diabetes (33 on eplerenone,
      36 on placebo). Eplerenone had no effect on new-onset diabetes [hazard ratio (HR)
      0.94, 95% confidence interval (CI) 0.59-1.52] and no effect on the composite of
      new-onset diabetes or mortality (HR 0.80, 95% CI 0.64-1.01). Independent
      predictors of new-onset diabetes included digoxin therapy, higher serum alanine
      aminotransferase, longer duration of heart failure, current or previous smoker,
      higher waist circumference, lower age, and higher systolic blood pressure with a
      combined c-statistic of 0.74. CONCLUSIONS: Eplerenone had no effect on new-onset
      diabetes in patients with CHF, but further large-scale studies are required to
      address this question comprehensively. Commonly recorded parameters provided
      useful information for predicting new-onset diabetes.

PMID- 22611048
TI  - Immunohistochemical detection of estrogen receptor, progesterone receptor and
      human epidermal growth factor receptor 2 in formalin-fixed breast carcinoma cell
      block preparations: correlation of results to corresponding tissue block (needle
      core and excision) samples.
AB  - Evaluation of ER, PR and Her 2 are routinely performed on breast carcinomas. For
      accurate detection of these markers, compliance with the ASCO/CAP guidelines is
      recommended. Our previous study showed that alcohol fixation did not affect ER
      results when alcohol-fixed cell block (CB) sections were compared to formalin
      fixed tissue sections, while PR and Her2 showed less concordance. The aim of this
      study was to evaluate and to compare ER, PR and Her2 IHC results on formalin
      fixed CB sections to those observed on subsequent surgical (needle core or
      resection) specimens (SS). Fifty cases of formalin fixed CB samples obtained from
      primary (18%) and metastatic (82%) breast carcinomas were studied, all of which
      had subsequent SS available. ER, PR, and Her2 IHC studies were done on all
      samples and results were compared. ER results on formalin-fixed CB samples showed
      excellent correlation with SS (correlation coefficient cc = 0.82). While there
      was minimal improvement in PR results (cc = 0.433), Her2 detection did not
      improve by formalin fixation (cc = 0.439). Formalin fixation for CB preparations
      does not significantly improve the already good detection of ER positive breast
      tumors. The concordance rate in PR and IHC results between formalin-fixed CB and
      SS samples showed improvement as compared with the alcohol-fixed CB results.
      However, there was no improvement in detection of Her2 overexpression by using
      formalin fixation on cytology specimens.

PMID- 22611051
TI  - Affinity-purification coupled to mass spectrometry: basic principles and
      strategies.
AB  - Identifying the interactions established by a protein of interest can be a
      critical step in understanding its function. This is especially true when an
      unknown protein of interest is demonstrated to physically interact with proteins
      of known function. While many techniques have been developed to characterize
      protein-protein interactions, one strategy that has gained considerable momentum
      over the past decade for identification and quantification of protein-protein
      interactions, is affinity-purification followed by mass spectrometry (AP-MS).
      Here, we briefly review the basic principles used in affinity-purification
      coupled to mass spectrometry, with an emphasis on tools (both biochemical and
      computational), which enable the discovery and reporting of high quality protein
      protein interactions.

PMID- 22611050
TI  - A pair of transmembrane receptors essential for the retention and pigmentation of
      hair.
AB  - Hair follicles are simple, accessible models for many developmental processes.
      Here, using mutant mice, we show that Bmpr2, a known receptor for bone
      morphogenetic proteins (Bmps), and Acvr2a, a known receptor for Bmps and
      activins, are individually redundant but together essential for multiple
      follicular traits. When Bmpr2/Acvr2a function is reduced in cutaneous epithelium,
      hair follicles undergo rapid cycles of hair generation and loss. Alopecia results
      from a failure to terminate hair development properly, as hair clubs never form,
      and follicular retraction is slowed. Hair regeneration is rapid due to premature
      activation of new hair-production programs. Hair shafts differentiate aberrantly
      due to impaired arrest of medullary-cell proliferation. When Bmpr2/Acvr2a
      function is reduced in melanocytes, gray hair develops, as melanosomes
      differentiate but fail to grow, resulting in organelle miniaturization. We
      conclude that Bmpr2 and Acvr2a normally play cell-type-specific, necessary roles
      in organelle biogenesis and the shutdown of developmental programs and cell
      division.

PMID- 22611052
TI  - Approach to improve compound recovery in a high-throughput Caco-2 permeability
      assay supported by liquid chromatography-tandem mass spectrometry.
AB  - The Caco-2 cell culture system is widely employed as an in vitro model for
      prediction of intestinal absorption of test compounds in early drug discovery.
      Poor recovery is a commonly encountered issue in Caco-2 assay, which can lead to
      difficulty in data interpretation and underestimation of the apparent
      permeability of affected compounds. In this study, we systematically investigated
      the potential sources of compound loss in our automated, high-throughput Caco-2
      assay, sample storage, and analysis processes, and as a result found the
      nonspecific binding to various plastic surfaces to be the major cause of poor
      compound recovery. To minimize the nonspecific binding, we implemented a simple
      and practical approach in our assay automation by preloading collection plates
      with organic solvent containing internal standard prior to transferring
      incubations samples. The implementation of this new method has been shown to
      significantly increase recovery in many compounds previously identified as having
      poor recovery in the Caco-2 permeability assay. With improved recovery,
      permeability results were obtained for many compounds that were previously not
      detected in the basolateral samples. In addition to recovery improvement, this
      new approach also simplified sample preparation for liquid chromatography-tandem
      mass spectrometric analysis and therefore achieved time and cost savings for the
      bioanalyst.

PMID- 22611053
TI  - (Implicitly) judging a book by its cover: the power of pride and shame
      expressions in shaping judgments of social status.
AB  - How do we decide who merits social status? According to functionalist theories of
      emotion, the nonverbal expressions of pride and shame play a key role,
      functioning as automatically perceived status signals. In this view, observers
      automatically make status inferences about expressers on the basis of these
      expressions, even when contradictory contextual information about the expressers'
      status is available. In four studies, the authors tested whether implicit and
      explicit status perceptions are influenced by pride and shame expressions even
      when these expressions' status-related messages are contradicted by contextual
      information. Results indicate that emotion expressions powerfully influence
      implicit and explicit status inferences, at times neutralizing or even overriding
      situational knowledge. These findings demonstrate the irrepressible communicative
      power of emotion displays and indicate that status judgments can be informed as
      much (and often more) by automatic responses to nonverbal expressions of emotion
      as by rational, contextually bound knowledge.

PMID- 22611054
TI  - When a threat to the brand is a threat to the self: the importance of brand
      identification and implicit self-esteem in predicting defensiveness.
AB  - This research examines how people respond when a commercial brand they identify
      with is threatened. Across four studies, the authors found that among
      participants who identified with a brand, a threat to the brand elicited the same
      responses as a threat to the self. Specifically, participants with low implicit
      self-esteem defended the brand when the self was activated, unlike their high
      implicit self-esteem counterparts. In addition, brand defense was reduced when
      individuals had the opportunity to affirm a valued aspect of their self-concept.
      These findings suggest that when a brand that people identify with is threatened,
      they may defend the brand to preserve the integrity of the self. More broadly,
      these findings are consistent with the notion that brands may be included into
      the extended self-concept, which supports William James's original ideas
      concerning the breadth and heterogeneity of the self.

PMID- 22611055
TI  - Reporting intentional rating of the primes predicts priming effects in the
      affective misattribution procedure.
AB  - In the affective misattribution procedure (AMP), pairs of prime and target
      stimuli appear rapidly in succession. Attitudes toward the prime influence the
      evaluation of the target despite instructions to avoid this influence. Because
      this priming effect presumably happens without people's knowledge, the AMP is
      used to study automatic evaluation. Participants in four studies performed the
      AMP and reported their perception of the priming effect. The authors found that
      the priming reflected reliable and valid attitudes toward the primes mostly among
      participants who reported that the priming occurred and that they intentionally
      rated the primes instead of the targets. The authors conclude that the AMP hardly
      captures attitude effects that escape people's knowledge. The AMP's good
      psychometric qualities as an attitude measure rely mainly on a small subset of
      participants who believe that they intentionally caused the attitude effect.

PMID- 22611056
TI  - Synchronous hepatocellular carcinoma and Castleman's disease: the role of the
      interleukin-6-signaling pathway.

PMID- 22611049
TI  - Lower serum hepcidin and greater parenchymal iron in nonalcoholic fatty liver
      disease patients with C282Y HFE mutations.
AB  - Hepcidin regulation is linked to both iron and inflammatory signals and may
      influence iron loading in nonalcoholic steatohepatitis (NASH). The aim of this
      study was to examine the relationships among HFE genotype, serum hepcidin level,
      hepatic iron deposition, and histology in nonalcoholic fatty liver disease
      (NAFLD). Single-nucleotide polymorphism genotyping for C282Y (rs1800562) and H63D
      (rs1799945) HFE mutations was performed in 786 adult subjects in the NASH
      Clinical Research Network (CRN). Clinical, histologic, and laboratory data were
      compared using nonparametric statistics and multivariate logistic regression.
      NAFLD patients with C282Y, but not H63D mutations, had lower median serum
      hepcidin levels (57 versus 65 ng/mL; P = 0.01) and higher mean hepatocellular
      (HC) iron grades (0.59 versus 0.28; P < 0.001), compared to wild-type (WT)
      subjects. Subjects with hepatic iron deposition had higher serum hepcidin levels
      than subjects without iron for all HFE genotypes (P < 0.0001). Hepcidin levels
      were highest among patients with mixed HC/reticuloendothelial system cell (RES)
      iron deposition. H63D mutations were associated with higher steatosis grades and
      NAFLD activity scores (odds ratio [OR], >=1.4; 95% confidence interval [CI]:
      >1.0, <=2.5; P <= 0.041), compared to WT, but not with either HC or RES iron.
      NAFLD patients with C282Y mutations had less ballooning or NASH (OR, <=0.62; 95%
      CI: >0.39, <0.94; P <= 0.024), compared to WT subjects. CONCLUSIONS: The presence
      of C282Y mutations in patients with NAFLD is associated with greater HC iron
      deposition and decreased serum hepcidin levels, and there is a positive
      relationship between hepatic iron stores and serum hepcidin level across all HFE
      genotypes. These data suggest that body iron stores are the major determinant of
      hepcidin regulation in NAFLD, regardless of HFE genotype. A potential role for
      H63D mutations in NAFLD pathogenesis is possible through iron-independent
      mechanisms.

PMID- 22611057
TI  - Molecular interaction databases.
AB  - Molecular interaction databases are playing an ever more important role in our
      understanding of the biology of the cell. An increasing number of resources exist
      to provide these data and many of these have adopted the controlled vocabularies
      and agreed-upon standardised data formats produced by the Molecular Interaction
      workgroup of the Human Proteome Organization Proteomics Standards Initiative
      (HUPO PSI-MI). Use of these standards allows each resource to establish PSI
      Common QUery InterfaCe (PSICQUIC) service, making data from multiple resources
      available to the user in response to a single query. This cooperation between
      databases has been taken a stage further, with the establishment of the
      International Molecular Exchange (IMEx) consortium which aims to maximise the
      curation power of numerous data resources, and provide the user with a non
      redundant, consistently annotated set of interaction data.

PMID- 22611058
TI  - Independent predictors of mortality in patients with advanced heart failure
      treated by cardiac resynchronization therapy.
AB  - AIMS: The current study includes all consecutive patients with advanced heart
      failure and cardiac resynchronization therapy (CRT) with an implantable
      cardioverter defibrillator (ICD) over a 10-year period in a tertiary referral
      centre. It aims at identifying independent risk factors for mortality during CRT
      defibrillator (CRT-D) treatment. METHODS AND RESULTS: This study includes 239
      consecutive patients who had undergone implantation of a CRT-D system (ejection
      fraction 25.9 +/- 8%; 139 patients with ischaemic, 100 patients with non
      ischaemic cardiomyopathy). Enrolment took place between 2001 and 2010, resulting
      in a median follow-up of 43 +/- 30 months. During follow-up, 59 patients (25%)
      died. An impaired baseline kidney function [hazard ratio (HR) 1.98; 95%
      confidence interval (CI) 1.7-3; P< 0.0001], appropriate ICD therapy during follow
      up (HR 2.1; CI 1.1-3.4; P= 0.001), lack of beta-blocker therapy (HR 2.3; CI 1.6
      3.8; P= 0.004), and intake of amiodarone (HR 2; CI 1.8-4.1; P< 0.0001) were
      identified as predictors of overall mortality. CONCLUSION: This study
      demonstrates the benefit of beta-blocker therapy also in patients on long-term
      CRT-D treatment. It confirms the prognostic significance of impaired renal
      function and the occurrence of appropriate ICD therapies also in CRT-D patients.
      It argues for an intensified follow-up regimen and adjustment of heart failure
      treatment whenever these prognostic markers are identified in a patient treated
      with CRT-D.

PMID- 22611059
TI  - The promise of immunisation against rotavirus.
AB  - Infectious diarrhoea is a common disease of childhood. It is estimated to be
      responsible for over 1.3 million deaths per year, predominantly in resource-poor
      countries. In wealthy nations, it causes significant morbidity, healthcare burden
      and associated cost. In both scenarios, the most common cause is rotavirus. This
      article reviews the experience of primary prevention of rotavirus disease through
      immunisation and considers the case for extending vaccine use further in Europe
      and globally.

PMID- 22611060
TI  - The natural history and predictors of persistent problem behaviours in cystic
      fibrosis: a multicentre, prospective study.
AB  - BACKGROUND: In cystic fibrosis (CF), problems with sleep, eating/mealtime
      behaviours, physiotherapy adherence and parental mental health issues are common,
      yet their natural history and the extent of service use to address them are
      unknown. OBJECTIVE: Follow up the 2007 cohort to determine: (1) prevalence of
      child sleep, eating/mealtime behaviours, physiotherapy adherence, and
      externalising/internalising problem behaviours and primary caregiver mental
      health status after a 3-year period; (2) natural history of child behaviours; (3)
      potentially modifiable predictors of persistent problems; and (4) service use for
      behaviours. DESIGN: Prospective cohort. SETTING: Royal Children's Hospital,
      Monash Medical Centre and Sydney Children's Hospital (Australia) CF clinics.
      PARTICIPANTS: Caregivers, of children aged 3-8 years, who completed the baseline
      questionnaire. MAIN OUTCOME MEASURES: Child sleep, eating/mealtime behaviours,
      adherence with therapy and externalising and internalising behaviours.
      PREDICTORS: parenting style (low warmth), caregiver mental health status and
      sleep quality at baseline. RESULTS: 102 of 116 (88%) families participated. The
      prevalence of sleep and eating/mealtime problems at follow-up was similar to
      baseline. The prevalence of caregiver mental health symptoms remained higher than
      the community data. 71 out of 102 (70%) of the children experienced at least one
      persistent behaviour problem. Caregiver mental health difficulties predicted
      persistent child moderate to severe sleep problems (adjusted OR 6.5, 95% CI 1.2
      to 36.2, p=0.03) and their persistently poor adherence to the physiotherapy
      regimen (adjusted OR 3.5, 95% CI 1.3 to 9.2, p=0.01). CONCLUSIONS: Child problem
      behaviours are common in children with CF, persist and are often predicted by the
      mental health of the parent. Routine surveillance for and management of child
      problem behaviours are recommended.

PMID- 22611061
TI  - Consent to tissue banking for research: qualitative study and recommendations.
AB  - OBJECTIVE: To explore how families of children with cancer experience giving
      consent for tissue banking and to produce recommendations on good practice.
      DESIGN: 79 participants from 42 families (41 mothers, 18 fathers, 20 children and
      young people with cancer) took part in semistructured interviews to explore their
      experiences of being approached for consent to tissue banking. SETTING: Tertiary
      care facilities for childhood cancer. RESULTS: Families are generally supportive
      of tissue banking, although they report that it may be difficult for them to
      consider all the implications when asked for consent. They typically do not want
      detailed information when consent is sought close to diagnosis, preferring to see
      tissue banking as part of routine practice. Families often recognise that their
      consent may not be fully informed, but are content to give consent based on their
      understanding at the time. Some may want a chance to go over the information and
      revisit their decision when things have settled. CONCLUSIONS: Families' views can
      inform practical recommendations for optimising the experience of consent for
      tissue banking. Current guidelines for obtaining consent should be revisited to
      take account of families' preferences.

PMID- 22611062
TI  - Neonatal hearing screening and intervention in resource-limited settings: an
      overview.
AB  - From a developmental perspective, optimal speech and language outcome is
      indisputably the primary motivation for neonatal hearing screening of infants
      with congenital or early-onset hearing loss (PCHL). This paper additionally
      outlines more broadly the potential value of early hearing detection and
      intervention in resource-poor countries against the backdrop of limitations of
      primary prevention of PCHL based on a review of literature from low-income and
      middle-income countries with per capita incomes of approximately US$6000 or less.
      It establishes the scientific and developmental foundation for priority
      consideration for neonatal hearing screening and intervention in any global
      initiatives for effective early childhood development programmes in resource
      limited countries. It also highlights approaches to addressing the various
      challenges to implementing effective early hearing detection and intervention
      programmes, and concludes with a discussion on the pivotal role of paediatricians
      in facilitating timely referral for requisite tests and (re)habilitative services
      especially for infants with established risk factors.

PMID- 22611063
TI  - Insights into the pathogenicity of rare missense GCK variants from the
      identification and functional characterization of compound heterozygous and
      double mutations inherited in cis.
AB  - OBJECTIVE: To demonstrate the importance of using a combined genetic and
      functional approach to correctly interpret a genetic test for monogenic diabetes.
      RESEARCH DESIGN AND METHODS: We identified three probands with a phenotype
      consistent with maturity-onset diabetes of the young (MODY) subtype GCK-MODY, in
      whom two potential pathogenic mutations were identified: [R43H/G68D], [E248
      K/I225M], or [G261R/D217N]. Allele-specific PCR and cosegregation were used to
      determine phase. Single and double mutations were kinetically characterized.
      RESULTS: The mutations occurred in cis (double mutants) in two probands and in
      trans in one proband. Functional studies of all double mutants revealed
      inactivating kinetics. The previously reported GCK-MODY mutations R43H and G68D
      were inherited from an affected father and unaffected mother, respectively. Both
      our functional and genetic studies support R43H as the cause of GCK-MODY and G68D
      as a neutral rare variant. CONCLUSIONS: These data highlight the need for
      family/functional studies, even for previously reported pathogenic mutations.

PMID- 22611064
TI  - Autonomic cardiac regulation during spontaneous nocturnal hypoglycemia in
      patients with type 1 diabetes.
AB  - OBJECTIVE: Experimental clamp studies have suggested that hypoglycemia evokes a
      reduction of cardiac vagal control in patients with type 1 diabetes. However,
      there are limited data on the influence of spontaneous nocturnal hypoglycemia on
      cardiac autonomic regulation. RESEARCH DESIGN AND METHODS: Adults with type 1
      diabetes (n = 37) underwent continuous glucose monitoring via a subcutaneous
      sensor as well as recording of R-R interval or electrocardiogram for 3 nights.
      Heart rate (HR) variability was analyzed during periods of hypoglycemia (glucose
      <3.5 mmol/L) (minimum length of 20 min) and a control nonhypoglycemic period
      (glucose >3.9 mmol/L) of equal duration and at the same time of night. RESULTS:
      The duration of hypoglycemic and control episodes (n = 18) ranged from 20 to 190
      min (mean 71 min). HR (62 +/- 7 vs. 63 +/- 9 beats per min; P = 0.30) or the high
      frequency component of HR power spectrum (2,002 +/- 1,965 vs. 1,336 +/- 1,506
      ms(2); P = 0.26) did not change during hypoglycemia. Hypoglycemia resulted in a
      significant decrease in the low-frequency component of HR variability (2,134 +/-
      1,635 vs. 1,169 +/- 1,029 ms(2), respectively; P = 0.006). The decline in the
      glucose concentration displayed a significant positive correlation with the
      decrease of the low-frequency component of HR variability (r = 0.48; P = 0.04).
      The latter was closely related to an increase in muscle sympathetic nerve
      activity recorded in 10 subjects during controlled sympathetic activation.
      CONCLUSIONS: Spontaneous nocturnal hypoglycemia in patients with type 1 diabetes
      results in a reduction of the low-frequency component of HR, which is best
      explained by excessive sympathetic activation without a concomitant withdrawal of
      vagal outflow.

PMID- 22611065
TI  - Health-related quality of life among German youths with early-onset and long
      duration type 1 diabetes.
AB  - OBJECTIVE: To evaluate self- and parent reports of general health status and
      health-related quality of life (QoL) in children and adolescents with early-onset
      and long-lasting type 1 diabetes compared with the general population in Germany.
      RESEARCH DESIGN AND METHODS: A total of 629 subjects aged 11 to 17 years, with a
      type 1 diabetes onset occurring from age 0 to 4 years during the years 1993-1999,
      and their parents, completed questionnaires, including the generic KINDL-R
      Questionnaire for Measuring Health-Related Quality of Life in Children and
      Adolescents, revised version, to assess QoL. The comparison group (n = 6,813) was
      a representative sample from the German Health Interview and Examination Survey
      for Children and Adolescents (KiGGS) study. Regression analyses were conducted
      using sociodemographic and health-related covariates. RESULTS: Intensified
      insulin therapy was used to treat 93% of children and adolescents with type 1
      diabetes. They reported "excellent" general health as often as peers (adjusted OR
      0.83 [95% CI 0.66-1.04] for an "excellent" rating), but the parent-rated general
      health was worse than that in the general population (OR 0.60 [0.48-0.74]). The
      patients reported increased self-esteem (adjusted difference beta = 4.39 [SE
      0.82]; P < 0.001) and well-being at school (beta = 3.41 [0.77]; P < 0.001) but
      lower well-being within their families (beta = -2.42 [0.80]; P = 0.002). The self
      and parent-reported total QoL did not differ between the patient group and the
      general population. The adjusted difference (SE) between the two samples in total
      QoL was beta = 0.89 (0.52; P = 0.087) in the self-reports and beta = -0.98 (0.53;
      P = 0.066) in the parent-reports. CONCLUSIONS: Compared with the general
      population, the QoL and general health status were not impaired among those aged
      11-17 years with early-onset type 1 diabetes, despite the challenges of modern
      therapy.

PMID- 22611066
TI  - Diabetes differentially affects depression and self-rated health by age in the
      U.S.
AB  - OBJECTIVE: To determine whether the relationship between age and physical and
      mental health varies by diabetes status in older U.S. adults. RESEARCH DESIGN AND
      METHODS: Using data from the National Social Life, Health, and Aging Project, a
      national sample of 3,005 adults aged 57-85 years, we tested the significance of
      the interaction between age and diabetes in association with health states.
      RESULTS: Respondents with diabetes in the youngest age cohort had more medical
      conditions than those without diabetes, a difference that narrowed with age (P
      for interaction <0.01). The youngest cohort with diabetes had a higher rate of
      depression compared to those without diabetes (14 vs. 8%). Depression declined
      with age and did not differ by diabetes status in the oldest respondents (P =
      0.01 for age-diabetes interaction). CONCLUSIONS: Diabetes differentially affects
      self-rated overall health and depression by age, with convergence in the oldest
      age-group with and without diabetes.

PMID- 22611068
TI  - A novel method for the determination of the site of glucuronidation by ion
      mobility spectrometry-mass spectrometry.
AB  - Glucuronidation not only plays a detoxifying role in living body, but it also can
      complicate pharmacological and toxicological profiles of new drug candidates by
      forming active and reactive conjugated metabolites. The opportunity to elucidate
      structure of conjugated metabolites has increased in drug metabolism studies at
      the early development stage. General methodologies for the structure elucidation
      of glucuronide conjugate(s) include liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) and NMR spectroscopy. In many cases, LC-MS/MS alone
      cannot unequivocally identify the site(s) of conjugation in isomeric
      glucuronidations. In the present study, we established a new strategy for the
      structure elucidation of glucuronide conjugates using ion mobility spectrometry
      (IMS)-mass spectrometry. Linear correlation between calculated collision cross
      sections (CCS) and actual drift times from IMS was found for each set of parent
      compound (raloxifene, losartan, telmisartan, and estradiol) and the corresponding
      MS/MS product ions. Thus, obtained regression lines accurately and selectively
      projected the actual drift times of authentic standards of glucuronide conjugate
      based on the theoretical CCS values. The established method was used for the
      accurate assignment of predominant formation of phenolic glucuronide conjugate
      (SCH 60663) in the isomeric (phenolic and benzylic) glucuronidations of ezetimibe
      in the incubated sample with cryopreserved human hepatocytes. This application
      demonstrates the potential to facilitate the structure identification of
      glucuronide conjugates at the early development stage of new drug candidates.

PMID- 22611067
TI  - Brain distribution and bioavailability of elacridar after different routes of
      administration in the mouse.
AB  - The objective of this study was to determine the bioavailability and disposition
      of elacridar (GF120918; N-(4-(2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2
      isoquinolinyl)ethyl)phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide)
      in plasma and brain after various routes of administration in the mouse.
      Elacridar is a potent inhibitor of P-glycoprotein and breast cancer resistance
      protein and has been used to examine the influence of these efflux transporters
      on drug distribution to brain. Friend leukemia virus strain B mice were
      administered 100 mg/kg elacridar either orally or intraperitoneally. The absolute
      bioavailability of elacridar after oral or intraperitoneal dosing was determined
      with respect to an intravenous dose of 2.5 mg/kg. At these doses, the absolute
      bioavailability was 0.22 for oral administration and 0.01 for intraperitoneal
      administration. The terminal half-life of elacridar was approximately 4 h after
      intraperitoneal and intravenous administration and nearly 20 h after oral dosing.
      The brain-to-plasma partition coefficient (Kp,brain) of elacridar increased as
      plasma exposure increased, suggesting saturation of the efflux transporters at
      the blood-brain barrier. The Kp,brain after intravenous, intraperitoneal, and
      oral dosing was 0.82, 0.43, and 4.31, respectively. The low aqueous solubility
      and high lipophilicity of elacridar result in poor oral absorption, most likely
      dissolution-rate-limited. These results illustrate the importance of the route of
      administration and the resultant plasma exposure in achieving effective plasma
      and brain concentrations of elacridar and can be used as a guide for future
      studies involving elacridar administration and in developing formulation
      strategies to overcome the poor absorption.

PMID- 22611069
TI  - Review: psychological and educational interventions may reduce risk of depressive
      disorders in children and adolescents.

PMID- 22611070
TI  - Review: exposure to premigration violence, gender and settlement location are
      associated with psychological problems among forcibly displaced children.

PMID- 22611071
TI  - Review: major depression affects about 7% of adults aged 75 and above.

PMID- 22611074
TI  - Novel, cyclic heat dissipation method for the correction of natural temperature
      gradients in sap flow measurements. Part 1. Theory and application.
AB  - Natural temperature gradient (NTG) can be a significant problem in thermal sap
      flow measurements, particularly in dry environments with sparse vegetation. To
      resolve this problem, we propose a novel correction method called cyclic heat
      dissipation (CHD) in its thermal dissipation probe (TDP) application. The CHD
      method is based on cyclic, switching ON/OFF power schema measurements and a three
      exponential model, extrapolating measured signal to steady state thermal
      equilibrium. The extrapolated signal OFF represents NTG, whereas the extrapolated
      signal ON represents standard TDP signal, biased by NTG. Therefore, subtraction
      of the OFF signal from the ON signal allows defining the unbiased TDP signal,
      finally processed according to standard Granier calibration. The in vivo Kalahari
      measurements were carried out in three steps on four different tree species,
      first as NTG, then as standard TDP and finally in CHD mode, each step for ~1-2
      days. Afterwards, each tree was separated from its stem following modified
      Roberts' (1977) procedure, and CHD verification was applied. The typical NTG
      varying from ~0.5  degrees C during night-time to -1  degrees C during day-time,
      after CHD correction, resulted in significant reduction of sap flux densities
      (J(p)) as compared with the standard TDP, particularly distinct for low J(p). The
      verification of the CHD method indicated ~20% agreement with the reference
      method, largely dependent on the sapwood area estimate. The proposed CHD method
      offers the following advantages: (i) in contrast to any other NTG correction
      method, it removes NTG bias from the measured signal by using in situ,
      extrapolated to thermal equilibrium signal; (ii) it does not need any specific
      calibration making use of the standard Granier calibration; (iii) it provides a
      physical background to the proposed NTG correction; (iv) it allows for power
      savings; (v) it is not tied to TDP, and so can be adapted to other thermal
      methods. In its current state, the CHD data processing is not yet fully
      automated.

PMID- 22611075
TI  - Left ventricular lead deployment using a transfemoral approach with subcutaneous
      tunnelling to a prepectoral pocket: a novel approach for upgrading to cardiac
      resynchronization therapy.

PMID- 22611076
TI  - An electrocardiographic proof of substrate modification during ablation of
      tetralogy of Fallot associated right ventricular tachycardia.

PMID- 22611077
TI  - Mediterranean diet and risk of hemorrhagic stroke: yes or no?

PMID- 22611078
TI  - Absorption and metabolism of red wine polyphenols and their potential health
      benefits in cardiovascular function.

PMID- 22611079
TI  - Protein requirements and the indicator amino acid oxidation method.

PMID- 22611080
TI  - Case of palm olein compared with lard and olive oil.

PMID- 22611081
TI  - Which additional factors may influence the maintenance of vitamin D status?

PMID- 22611083
TI  - Insulin resistance improves metabolic and contractile efficiency in stressed rat
      heart.
AB  - Insulin resistance is a prominent feature in heart failure, while hyperglycemia
      impairs cardiac contraction. We propose that decreased insulin-mediated glucose
      uptake by the heart preserves cardiac function in response to metabolic and
      hemodynamic stress. To test this hypothesis, we fed rats a high-sucrose diet
      (HSD). Energy substrate metabolism and cardiac work were determined ex vivo in a
      sequential protocol simulating metabolic and hemodynamic stress. Compared to chow
      fed, control rats, HSD impaired myocardial insulin responsiveness and induced
      profound metabolic changes in the heart, characterized by reduced rates of
      glucose uptake (7.91 +/- 0.30 vs. 10.73 +/- 0.67 MUmol/min/g dry weight; P<0.001)
      but increased rates of glucose oxidation (2.38 +/- 0.17 vs. 1.50 +/- 0.15
      MUmol/min/g dry weight; P<0.001) and oleate oxidation (2.29 +/- 0.11 vs. 1.96 +/-
      0.12 MUmol/min/g dry weight; P<0.05). Tight coupling of glucose uptake and
      oxidation and improved cardiac efficiency were associated with a reduction in
      glucose 6-phosphate and oleoyl-CoA levels, as well as a reduction in the content
      of uncoupling protein 3. Our results suggest that insulin resistance lessens fuel
      toxicity in the stressed heart. This calls for a new exploration of the
      mechanisms regulating substrate uptake and oxidation in the insulin-resistant
      heart.

PMID- 22611084
TI  - A multicomponent sugar phosphate sensor system specifically induced in Bacillus
      cereus during infection of the insect gut.
AB  - Using a previously developed Bacillus cereus in vivo expression technology (IVET)
      promoter trap system, we showed that spsA, a gene of unknown function, was
      specifically expressed in the larval gut during infection. Search for gut-related
      compounds inducing spsA transcription identified glucose-6-phosphate (G6P) as an
      activation signal. Analysis of the spsA-related 5-gene cluster indicated that
      SpsA is part of a new sugar phosphate sensor system composed of a 2-component
      system (TCS) encoded by spsR and spsK, and 2 additional downstream genes, spsB
      and spsC. In B. cereus, American Type Culture Collection (ATCC) 14579, spsRK, and
      spsABC are separate transcriptional units, of which only spsABC was activated by
      extracellular G6P. lacZ transcriptional fusions tested in mutant and complemented
      strains showed that SpsRK, SpsA, and SpsB are essential for the transcription of
      spsABC. Deletion mutant analysis showed that SpsC is essential for the G6P
      uptake. gfp-transcriptional fusions showed that these genes are required for host
      activated expression, as well. This sugar phosphate sensor and transport system
      is found in pathogenic Bacillus group and Clostridia bacteria and may be
      important for host adaptation. Our findings provide new insights into the
      function of 2-component sensor systems in host-pathogen interactions,
      specifically in the gut.

PMID- 22611085
TI  - CCN2/CTGF regulates neovessel formation via targeting structurally conserved
      cystine knot motifs in multiple angiogenic regulators.
AB  - Blood vessels are formed during development and tissue repair through a plethora
      of modifiers that coordinate efficient vessel assembly in various cellular
      settings. Here we used the yeast 2-hybrid approach and demonstrated a broad
      affinity of connective tissue growth factor (CCN2/CTGF) to C-terminal cystine
      knot motifs present in key angiogenic regulators Slit3, von Willebrand factor,
      platelet-derived growth factor-B, and VEGF-A. Biochemical characterization and
      histological analysis showed close association of CCN2/CTGF with these regulators
      in murine angiogenesis models: normal retinal development, oxygen-induced
      retinopathy (OIR), and Lewis lung carcinomas. CCN2/CTGF and Slit3 proteins worked
      in concert to promote in vitro angiogenesis and downstream Cdc42 activation. A
      fragment corresponding to the first three modules of CCN2/CTGF retained this
      broad binding ability and gained a dominant-negative function. Intravitreal
      injection of this mutant caused a significant reduction in vascular obliteration
      and retinal neovascularization vs. saline injection in the OIR model. Knocking
      down CCN2/CTGF expression by short-hairpin RNA or ectopic expression of this
      mutant greatly decreased tumorigenesis and angiogenesis. These results provided
      mechanistic insight into the angiogenic action of CCN2/CTGF and demonstrated the
      therapeutic potential of dominant-negative CCN2/CTGF mutants for
      antiangiogenesis.

PMID- 22611087
TI  - Using ortholog sequence data to predict the functional relevance of mutations in
      G-protein-coupled receptors.
AB  - Evaluating the functional relevance of naturally occurring gene variants usually
      requires experimental testing or is even impossible because of the lack of
      appropriate functional assays. Here we have analyzed whether comparative sequence
      data from orthologs are suitable to predict the functional relevance of mutations
      in a model protein, a G-protein-coupled receptor for ADP (P2Y(12)). The
      functional effect of every possible substitution at each amino acid position
      within a portion of P2Y(12) (1254 mutants) was individually determined. Sequence
      analysis of >70 P2Y(12) vertebrate orthologs revealed that this amino acid
      variability ensuring proper receptor function in vivo highly correlates (>90%)
      with the in vitro experimental data. Therefore, ortholog sequence data are
      helpful to predict the functional relevance of individual positions and mutations
      for P2Y(12). It is likely that similar conclusions may be extended for other
      GPCRs and conserved proteins as well.

PMID- 22611086
TI  - The clock gene, brain and muscle Arnt-like 1, regulates adipogenesis via Wnt
      signaling pathway.
AB  - Circadian clocks in adipose tissue are known to regulate adipocyte biology.
      Although circadian dysregulation is associated with development of obesity, the
      underlying mechanism has not been established. Here we report that disruption of
      the clock gene, brain and muscle Arnt-like 1 (Bmal1), in mice led to increased
      adipogenesis, adipocyte hypertrophy, and obesity, compared to wild-type (WT)
      mice. This is due to its cell-autonomous effect, as Bmal1 deficiency in embryonic
      fibroblasts, as well as stable shRNA knockdown (KD) in 3T3-L1 preadipocyte and
      C3H10T1/2 mesenchymal stem cells, promoted adipogenic differentiation. We
      demonstrate that attenuation of Bmal1 function resulted in down-regulation of
      genes in the canonical Wnt pathway, known to suppress adipogenesis. Promoters of
      these genes (Wnt10a, beta-catenin, Dishevelled2, TCF3) displayed Bmal1 occupancy,
      indicating direct circadian regulation by Bmal1. As a result, Wnt signaling
      activity was attenuated by Bmal1 KD and augmented by its overexpression.
      Furthermore, stabilizing beta-catenin through Wnt ligand or GSK-3beta inhibition
      achieved partial restoration of blunted Wnt activity and suppression of increased
      adipogenesis induced by Bmal1 KD. Taken together, our study demonstrates that
      Bmal1 is a critical negative regulator of adipocyte development through
      transcriptional control of components of the canonical Wnt signaling cascade, and
      provides a mechanistic link between circadian disruption and obesity.

PMID- 22611088
TI  - The relationship of antidepressant prescribing concentration to treatment
      duration and cost.
AB  - BACKGROUND: Widely accepted treatment guidelines and performance measures
      encourage patients to stay on antidepressant medication beyond the acute phase of
      treatment in order to achieve full remission and reduce risk of relapse. However,
      many patients discontinue antidepressant medication treatment prematurely for
      various reasons, including side-effects or nonresponse to the initial medication
      prescribed. Customization of medications to differing patient profiles could
      potentially improve medication treatment duration, but for many diseases
      physicians tend to concentrate on a limited subset of available medications.
      Little is known about the effects of concentration in prescribing on medication
      treatment duration and expenditures. AIMS OF THE STUDY: To determine the extent
      to which prescribing for treatment of depression is concentrated, using data from
      a privately insured population. To evaluate the relationship between prescribing
      concentration and subsequent duration of medication treatment, expenditure on
      medications, and the number of distinct medications used. STUDY POPULATION:
      Individuals receiving antidepressant treatment paid for by a large private
      managed behavioral health organization, in the US. METHODS: The study uses
      psychotropic pharmacy claims data for 2003-06 for plan members who received a
      depression diagnosis and had an antidepressant claim. The resulting sample
      includes 9,017 patients seen by 543 prescribers. For each prescriber, we compute
      prescribing concentration, using the Herfindahl index and the share for the three
      most-used medications. Treatment expenditure is computed as the sum of payments
      by plan and by patients. Regression analysis is used to identify the association
      of prescribing concentration with medication treatment duration, expenditures and
      other utilization measures. RESULTS: For these physicians, the mean share of the
      physician's total antidepressant prescribing accounted for by their three most
      used regimens was 72%. The mean value of the Herfindahl index was 0.27. Over the
      180-day follow-up period, the average patient had 103 days covered by
      antidepressant prescriptions, resulting in mean expenditures of $286, or $2.25
      per day of medication supplied. Regression analysis indicates that higher
      concentration in a physician's prescribing was associated with fewer days of
      antidepressant coverage, lower medication expenditures, and subsequent use of
      fewer distinct medications. DISCUSSION: Higher concentration in prescribing is
      associated with shorter observed duration of medication treatment and lower
      expenditures on medications. The lower expenditures appear to be due to earlier
      discontinuation and fewer different medications, not to a lower cost per day
      supplied. Limitations of this study include lack of data on medical visits or on
      reasons for medication discontinuation, as the study is based on pharmacy claims
      data, not medical claims or surveys. In addition, it is not known whether the
      patient's antidepressant use represents a new episode. Finally, lack of
      randomization implies that the associations identified may not be causal.
      IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: Concentration of physicians on
      certain medications may run counter to the increasing calls for customization of
      medication selection. IMPLICATIONS FOR HEALTH POLICY: Insurer policies which
      limit physicians' choice of medications may be lowering expenditures in part by
      reducing patients' medication treatment duration. IMPLICATIONS FOR FURTHER
      RESEARCH: Additional studies are needed to understand what mechanisms may link
      concentration in prescribing to medication treatment duration and expenditures.

PMID- 22611089
TI  - The cost-effectiveness of short-term psychodynamic psychotherapy and solution
      focused therapy in the treatment of depressive and anxiety disorders during a one
      year follow-up.
AB  - BACKGROUND: Mood and anxiety disorders are characterized by a high and increasing
      prevalence, they cause a lot of costs and human suffering and there are many
      treatment options with differing costs. The benefits of identifying the
      treatments with the most favourable cost-effectiveness ratios can be substantial.
      However, the number of randomized trials where psychological treatments are
      compared with each other and where economic aspects, too, are taken into account
      is still relatively small. AIM: To compare the cost-effectiveness of two short
      term psychotherapies in the treatment of depressive and anxiety disorders during
      a one-year follow-up. METHODS: In the Helsinki Psychotherapy Study, 198 patients,
      who were 20--45 years of age and met DSM-IV criteria for anxiety or mood
      disorder, were randomized to short-term psychodynamic psychotherapy (SPP) or
      solution-focused therapy (SFT). Psychiatric symptoms were assessed at baseline
      and 4 times during the one-year follow-up from the start of therapy using the
      Beck Depression Inventory and the Symptom Check List Anxiety Scale, and 2 times
      using the Hamilton Depression Rating Scales and Hamilton Anxiety Rating Scales.
      Both direct costs (therapy sessions, outpatient visits, medication, inpatient
      care) and indirect costs (production losses due to work absenteeism, value of
      neglected household work, lost leisure time and unpaid help received) due to
      mental disorders were measured. Mean total costs were compared and incremental
      cost-effectiveness ratios analyzed. RESULTS: According to all 4 psychiatric
      outcome measures, symptoms of depression and anxiety were reduced statistically
      significantly in both therapy groups during the one-year follow-up. The relative
      changes were about the same size according to all four outcome measures. In both
      groups the reductions took place mainly in the first half of the follow-up. The
      reductions were somewhat greater with SPP, but the differences between the two
      groups were small and not statistically significant at any measurement point. The
      mean total direct costs were 1791 euros in the SPP group, being 346 euros (16%)
      lower than those of the SFT group, but this difference was not statistically
      significant either. Also the incremental cost-effectiveness ratio points
      calculated by 500 bootstrap iterations favoured SPP. The total indirect costs in
      the SPP group were, in contrast to direct costs, higher than those in the SFT
      group, but, again, the difference was not statistically significant. LIMITATIONS:
      The generalization of our results may be weakened by the fact that the patients
      included in our study were relatively young, and the follow-up period was
      restricted to one year. IMPLICATIONS: This study suggests that there are no
      notable differences in cost-effectiveness between SPP and SFT. If one were
      obliged to choose between these two therapies our results would support the
      choice of SPP. However, more research with extensive data about both costs and
      effectiveness, compiled over a period longer than one year, are needed before any
      firm conclusions can be drawn about the cost-effectiveness of the two therapies
      compared in this study.

PMID- 22611090
TI  - Economic burden of schizophrenia: empirical analyses from a survey in Thailand.
AB  - BACKGROUND: Evidence consistently indicates that schizophrenia is a costly
      disease although it is not a high prevalence disorder. There are a few studies in
      developing countries but no study in Thailand reporting the cost of schizophrenia
      from a societal perspective. Health policy makers need to be aware of the cost of
      health care for people with schizophrenia as well as the economic burden on
      patients and families. AIMS OF THE STUDY: This study aims to provide a detailed
      breakdown of the costs attributed to schizophrenia including the consumption of
      public health care resources by people with schizophrenia and the negative
      consequences on patients and families due to productivity losses. METHODS: Data
      from a survey conducted in 2008 among people in treatment for schizophrenia were
      used to estimate annual medical costs for treatment including outpatient
      services, hospitalization and patient travel. Indirect costs were estimated for
      reported productivity losses of patients and families. Uncertainty analysis was
      performed using Monte Carlo simulation methods. We tested the sensitivity of
      varying assumptions about market wages to estimate productivity losses. All cost
      estimates are adjusted to 2008 using the Consumer Price Index and reported in
      Thai baht (THB). The average annual exchange rate of Thai baths to one US dollar
      was 33.5 in 2008. RESULTS: The annual overall cost of schizophrenia was estimated
      to be THB 87 000 (USD 2600) (95% CI: 83 000, 92 000) per person or THB 31 000
      million (USD 925 million) (95% CI: 26 000, 37 000) for the entire population with
      schizophrenia in Thailand. Indirect costs due to high unemployment, absenteeism
      and presenteeism of patients and families accounted for 61% of the total economic
      burden of schizophrenia. The largest component of direct medical cost was for
      hospitalizations (50%), followed by outpatient services and drug costs.
      Sensitivity analyses suggest that using labor force survey and socioeconomic
      status survey provided similar results, while lost productivity when the minimum
      wage was used was significantly less. DISCUSSION: Productivity loss due to
      unemployment is the major contributor to the cost of schizophrenia. Due to data
      unavailability we did not include intangible costs (e.g. costs associated with
      pain and suffering or impact on quality of life) and direct non-health care costs
      (e.g. costs related to law enforcement and the criminal justice system). The
      survey sample is representative of only people who were in contact with mental
      health services and is not necessarily representative of all people with
      schizophrenia. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: In priority
      setting it is important that policy makers are aware of the high direct and
      indirect costs of schizophrenia. Providing optimal treatment (e.g. medication in
      combination with psychosocial interventions) could reduce some costs such has
      hospitalization but this may require increased investment in mental health care
      and time spent by patients and caregivers.

PMID- 22611091
TI  - Mood and sleep problems in adolescents and young adults: an econometric analysis.
AB  - BACKGROUND: Sleep related problems affect approximately 25-40% of children and
      adolescents. The acquisition of sleep patterns characterised by later bedtimes,
      insomnia and excessive daytime sleepiness is related to poorer school
      performance, daytime drowsiness, physical tiredness and a higher rate of
      psychiatric illnesses. Many studies have investigated the correlation between
      sleep and mood in children and adolescents and overall, show a positive
      association between sleep problems and psychiatric disorders. However, little is
      known about adolescents' personal perception of their psychological status as it
      is linked with the occurrence of mood changes and sleep-related problems. AIMS OF
      THE STUDY: The aim of the study is to explore the impact of variables such as
      age, gender, education and the perception of their own psychological status
      (evaluated through suitable questionnaires) on the simultaneous presence of sleep
      disturbances and affective symptoms in a sample of adolescents. A positive
      correlation between these two dependent variables signals the need to intervene
      with proper support programs. METHODS: A recursive bivariate probit model has
      been employed. This method allows us to take into account two dependent dummy
      variables and to consider the relationship between the two, presuming that one
      may also influence the other. The analysis has been carried out on a sample of
      2,005 adolescents out of a total of 4,000 who declared their willingness to be
      telephonically interviewed using a questionnaire in two parts designed to obtain
      information about the participants sleep habits and affective symptoms. RESULTS:
      There is a positive correlation between sadness and daytime drowsiness. The
      estimated joint probability ranging from 5.5% to 9% in girls demonstrates a
      greater tendency for girls to experience both depression and altered sleep
      patterns.  DISCUSSION AND LIMITATIONS OF THE STUDY: Just as sadness is a key
      symptom of affective disorders, daytime drowsiness indicates the presence of
      sleep disorders caused by sleep habits that are likely to evolve into affective
      symptoms. This assumption is confirmed by the results of this analysis. However,
      since the interviews were conducted during the years 2003 and 2004, a replication
      of the analysis would outline whether this evidence is still the same or whether
      changes in habits and behaviours have intervened to modify substantially this
      pattern in recent years. As the analysis considers a sample of adolescents living
      in two southern Italian regions, the study should be replicated in other
      geographical areas. IMPLICATIONS FOR HEALTH CARE PROVISIONS AND USE: The early
      detection of affective symptoms in adolescents may presumably lead to a
      diminished use of antidepressants and an improvement in learning abilities and
      school results along with strengthening of personal motivations. IMPLICATIONS FOR
      HEALTH POLICIES: Counselling and educational programs directed towards those
      adolescents demonstrating poor sleep habits should be planned and implemented to
      avoid further complications and impact on their mental health.

PMID- 22611092
TI  - Sustained virological response after 14-day treatment with danoprevir and 48-week
      treatment with pegylated interferon-alpha2a (40 KD) plus ribavirin.
AB  - BACKGROUND: Danoprevir (RG7227) is an inhibitor of the HCV NS3/4A protease. In
      two Phase Ib studies of treatment-naive patients with chronic HCV genotype 1
      infection, danoprevir administration for 14 days was associated with HCV RNA
      median reduction reaching 3.8 log(10) in monotherapy and 5.7 log(10) in
      combination therapy with pegylated interferon (PEG-IFN)-alpha2a (40 KD) plus
      ribavirin (RBV). After the protocol-defined phase, patients were free to continue
      with PEG-IFN/RBV. Sustained virological response (SVR) was evaluated in patients
      who continued treatment with PEG-IFN/RBV. METHODS: Retrospective analysis of the
      patients who received a 14-day monotherapy regimen with danoprevir (100 or 200 mg
      every 8 or 12 h), or 14-day triple therapy with danoprevir (100, 200 or 300 mg
      every 8 h, or 400, 600 or 900 mg every 12 h) with PEG-IFN-alpha2a (40 KD; 180
      MUg/week subcutaneously) and RBV (1,000-1,200 mg/day) followed by PEG-IFN-alpha2a
      (40 KD; 180 MUg/week subcutaneously) and RBV (1,000-1,200 mg/day) for 46 weeks
      (triple therapy group) for a total of 48 weeks (monotherapy group). RESULTS: Data
      were collected from 15 patients with danoprevir monotherapy and 24 patients with
      danoprevir-based triple therapy. Virological results are expressed using an
      intention-to-treat principle. Premature treatment discontinuation occurred in
      five patients. Rapid virological response (RVR; week 4) rate was 50% and 69.6%
      and SVR rate was 60% and 70.8% in the monotherapy and triple therapy groups,
      respectively. RVR was highly predictive of SVR (>90%; HCV RNA<15 IU/ml).
      CONCLUSIONS: The addition of danoprevir for 14 days to PEG-IFN/RBV treatment
      results in a high SVR rate in HCV genotype 1 treatment-naive patients.

PMID- 22611093
TI  - Deformation experiments in the diamond-anvil cell: texture in copper to 30 GPa.
AB  - The combination of the diamond-anvil cell, synchrotron x-ray diffraction in
      radial geometry and simultaneous Rietveld refinement with texture analysis allows
      us to quantitatively investigate the plastic deformation behaviour of materials
      at very high pressures. Our study of copper to 30 GPa shows in ideal experimental
      geometry a [110] fibre texture component, as is typical for axial compression of
      soft face centred cubic metals. Locally a plane strain texture develops which is
      energetically favoured (curling). A transition from compressional to plane
      strain/pure shear texture can be monitored by analysing individual images taken
      at different positions in the diamond cell.

PMID- 22611094
TI  - Numerical study of pressure relationships between sample and calibrant inside the
      diamond anvil cell.
AB  - We present isotropic, elastic-plastic finite element calculations detailing the
      pressure relationship between an inclusion and its surrounding matrix, subject to
      an externally imposed hydrostatic strain. In general, the inclusion and the
      matrix have different values of hydrostatic pressure, depending on their absolute
      and relative values of Young's modulus and Poisson's ratio. A series of finite
      element models was used to explore the parameter space of the elastic and plastic
      properties of an inclusion within a matrix. In all cases where there is
      insufficient relaxation of the nonhydrostatic stress, the material with the
      higher bulk modulus will also have a higher pressure, regardless of the shear
      moduli. The complete data set was subjected to a Pareto analysis to determine the
      main and secondary effects which influence the final result, expressed as the
      ratio of the pressure of the matrix to that of the inclusion. The four most
      important factors which determine the pressure ratio of an inclusion and matrix
      are the Young's modulus of the matrix, the interaction of the Young's modulus and
      the yield strength of the matrix material, the Young's modulus of the inclusion,
      and the interaction of the Young's modulus of the inclusion with the yield
      strength of the matrix material. The yield strength of the inclusion has a
      statistically insignificant effect on the results. This information provides
      guidelines for designing the most effective combinations of unknowns and material
      standards to minimize pressure errors in equation of state measurements.

PMID- 22611095
TI  - Do Reuss and Voigt bounds really bound in high-pressure rheology experiments?
AB  - Energy dispersive synchrotron x-ray diffraction is carried out to measure
      differential lattice strains in polycrystalline Fe(2)SiO(4)  (fayalite) and MgO
      samples using a multi-element solid state detector during high-pressure
      deformation. The theory of elastic modelling with Reuss (iso-stress) and Voigt
      (iso-strain) bounds is used to evaluate the aggregate stress and weight
      parameter, alpha  (0<=alpha<=1), of the two bounds. Results under the elastic
      assumption quantitatively demonstrate that a highly stressed sample in high
      pressure experiments reasonably approximates to an iso-stress state. However,
      when the sample is plastically deformed, the Reuss and Voigt bounds are no longer
      valid (alpha  becomes beyond 1). Instead, if plastic slip systems of the sample
      are known (e.g. in the case of MgO), the aggregate property can be modelled using
      a visco-plastic self-consistent theory.

PMID- 22611096
TI  - Measurement of stress using synchrotron x-rays.
AB  - Stress analysis in polycrystalline materials reveals that stress can vary
      considerably among different subpopulations of grains. Samples of MgO and
      mixtures of MgO and spinel have been studied. After the onset of plastic flow,
      stronger grains or orientations will support more stress than the weaker grains.
      A grain to grain fabric develops that enables this stress partitioning. The
      stress partitioning and the resulting fabric can invalidate static measurements
      of elastic moduli. However, high temperature flow mechanisms reveal a more
      isotropic strength behaviour resulting in a more uniform variation of stress with
      orientation.

PMID- 22611097
TI  - Ultrahigh-pressure experiment with a motor-driven diamond anvil cell.
AB  - A Pt sample was compressed to ultrahigh pressures in a diamond anvil cell (DAC)
      using a motorized gearbox to change pressure remotely from outside the
      synchrotron x-ray hutch. In situ angle-dispersive x-ray diffraction (XRD) was
      used to determine pressure from known equations of state (EOS). The sample
      position was unperturbed during motor-driven pressure changes. By eliminating the
      need to realign the sample to the x-ray position after each pressure increment,
      142 XRD patterns could be collected continuously over the course of three hours,
      and the maximum pressure of 230 GPa was reached before diamond failure ended the
      experiment. We demonstrate the advantages of this motor-driven assembly for
      smooth and efficient pressure change, and the possibility for fine pressure and
      temporal resolution.

PMID- 22611098
TI  - Effect of shear strain on the alpha-epsilon  phase transition of iron: a new
      approach in the rotational diamond anvil cell.
AB  - The effect of shear strain on the iron alpha-epsilon  phase transformation has
      been studied using a rotational diamond anvil cell (RDAC). The initial transition
      is observed to take place at the reduced pressure of 10.8 GPa under pressure and
      shear operation. Complete phase transformation was observed at 15.4 GPa. The
      rotation of an anvil causes limited pressure elevation and makes the pressure
      distribution symmetric in the sample chamber before the phase transition.
      However, it causes a significant pressure increase at the centre of the sample
      and brings about a large pressure gradient during the phase transformation. The
      resistance to the phase interface motion is enhanced due to strain hardening
      during the pressure and shear operations on iron and this further increases the
      transition pressure. The work of macroscopic shear stress and the work of the
      pressure and shear stress at the defect tips account for the pressure reduction
      of the iron phase transition.

PMID- 22611099
TI  - Diamond-anvil cell for radial x-ray diffraction.
AB  - We have designed a new diamond-anvil cell capable of radial x-ray diffraction to
      pressures of a few hundred GPa. The diffraction geometry allows access to
      multiple angles of Psi, which is the angle between each reciprocal lattice vector
      g(hkl)  and the compression axis of the cell. At the 'magic angle', Psi~54.7
      degrees , the effects of deviatoric stresses on the interplanar spacings, d(hkl),
      are significantly reduced. Because the systematic errors, which are different for
      each d(hkl), are significantly reduced, the crystal structures and the derived
      equations of state can be determined reliably. At other values of Psi, the
      effects of deviatoric stresses on the diffraction pattern could eventually be
      used to determine elastic constants.

PMID- 22611100
TI  - Diamond anvil cell radial x-ray diffraction program at the National Synchrotron
      Light Source.
AB  - During the past decade, the radial x-ray diffraction method using a diamond anvil
      cell (DAC) has been developed at the X17C beamline of the National Synchrotron
      Light Source. The detailed experimental procedure used with energy dispersive x
      ray diffraction is described. The advantages and limitations of using the energy
      dispersive method for DAC radial diffraction studies are also discussed. The
      results for FeO at 135 GPa and other radial diffraction experiments performed at
      X17C are discussed in this report.

PMID- 22611101
TI  - Double-sided laser heating system at HPCAT for in situ x-ray diffraction at high
      pressures and high temperatures.
AB  - An overview of a YLF:Nd laser heating system at the undulator x-ray diffraction
      station (16ID-B) of the high-pressure collaborative access team (HPCAT) of the
      Advanced Photon Source is presented. Based on the double-sided laser heating
      technique, the system is designed with considerable effort on the mechanical and
      optical stabilities, features for user-friendly operation, and the capability of
      accommodating diamond anvil cells of various heights up to 68 mm. This system has
      been used for x-ray diffraction studies of a wide range of materials to over 150
      GPa and above 3000 K. Applying the laser heating technique to radial x-ray
      diffraction studies at simultaneous high-pressure and high-temperature (PT)
      conditions requires heating to be conducted at variable angles relative to the x
      ray direction. A rotation laser heating design is discussed.

PMID- 22611102
TI  - Deviatoric stress: a nuisance or a gold mine?
AB  - Both synchrotron radiation and deviatoric stress were once considered to be
      nuisances. Now synchrotron radiation is one of the most important tools available
      to scientists of all disciplines and deviatoric stress is one of the most useful
      aspects of x-ray diffraction at extreme conditions. Samples in high-pressure
      devices are under true hydrostatic pressure only when surrounded by a fluid, thus
      limiting true hydrostatic pressure studies at ambient temperatures to pressures
      below about 11 GPa. Elevated temperature is able to extend this limit but has
      rarely been used for this purpose. Instead, noble gases have been used as
      pressure media as their solids are especially soft. Deviatoric stress and
      resultant anisotropic elastic strain in solid samples and solid media have led to
      many subtle errors in determinations of elastic properties and crystal
      structures, especially in the days before it was realized that they could be
      measured and were potentially a valuable source of information. In recent years,
      measuring anisotropic elastic strain by x-ray diffraction has provided new
      insights into materials strength, elastic properties, crystal structures,
      mechanisms of phase transitions, slip systems, lattice preferred orientation,
      and, of course, ways to make corrections when deviatoric stress is indeed a
      nuisance.

PMID- 22611103
TI  - Deformation textures produced in diamond anvil experiments, analysed in radial
      diffraction geometry.
AB  - Diamond anvil cells may not only impose pressure upon a sample but also a
      compressive stress that produces elastic and plastic deformation of
      polycrystalline samples. The plastic deformation may result in texture
      development if the material deforms by slip or mechanical twinning, or if grains
      have a non-equiaxed shape. In radial diffraction geometry, texture is revealed by
      variation of intensity along Debye rings relative to the compression direction.
      Diffraction images (obtained by CCD or image plate) can be used to extract
      quantitative texture information. Currently the most elegant and powerful method
      is a modified Rietveld technique as implemented in the software package MAUD.
      From texture data one can evaluate the homogeneity of strain in a diamond anvil
      cell, the strain magnitude and deformation mechanisms, the latter by comparing
      observed texture patterns with results from polycrystal plasticity simulations.
      Some examples such as olivine, magnesiowuestite, MgSiO(3) perovskite and epsilon
      iron are discussed.

PMID- 22611104
TI  - X-ray diffraction evaluation of stress in high pressure deformation experiments.
AB  - This paper explores the applicability of x-ray diffraction measurements of stress
      to high pressure deformation experiments. We model measurements of elastic
      lattice strains in various geometries for both axial and rotational deformation
      apparatus. We then show that, for most cases, stresses can be inverted from the
      diffraction data. A comparison between the results of our models and actual
      experimental data also indicates that plastic deformation can have an influence
      that is not addressed properly in the elastic models of lattice strains and
      should therefore be treated with caution.

PMID- 22611105
TI  - Strength, anisotropy, and preferred orientation of solid argon at high pressures.
AB  - The elasticity and plasticity of materials at high pressure are of great
      importance for the fundamental insight they provide on bonding properties in
      dense matter and for applications ranging from geophysics to materials
      technology. We studied pressure-solidified argon with a boron-epoxy-beryllium
      composite gasket in a diamond anvil cell (DAC). Employing monochromatic
      synchrotron x-radiation and imaging plates in a radial diffraction geometry
      (Singh et al 1998 Phys. Rev. Lett. 80 2157; Mao et al 1998 Nature 396 741), we
      observed low strength in solid argon below 20 GPa, but the strength increases
      drastically with applied pressure, such that at 55 GPa, the shear strength
      exceeded 2.7 GPa. The elastic anisotropy at 55 GPa was four times higher than the
      extrapolated value from 30 GPa. Extensive (111) slip develops under uniaxial
      compression, as manifested by the preferred crystallographic orientation of (220)
      in the compression direction. These macroscopic properties reflect basic changes
      in van der Waals bondings under ultrahigh pressures.

PMID- 22611106
TI  - Nonhydrostatic compression of gold powder to 60 GPa in a diamond anvil cell:
      estimation of compressive strength from x-ray diffraction data.
AB  - Two gold powder samples, one with average crystallite size of ~30 nm (n-Au) and
      another with ~120 nm (c-Au), were compressed under nonhydrostatic conditions in a
      diamond anvil cell to different pressures up to ~60 GPa and the x-ray diffraction
      patterns recorded. The difference between the axial and radial stress components
      (a measure of the compressive strength) was estimated from the shifts of the
      diffraction lines. The maximum micro-stress in the crystallites (another measure
      of the compressive strength) and grain size (crystallite size) were obtained from
      analysis of the line-width data. The strengths obtained by the two methods agreed
      well and increased with increasing pressure. Over the entire pressure range, the
      strength of n-Au was found to be significantly higher than that of c-Au. The
      grain sizes of both n-Au and c-Au decreased under pressure. This decrease was
      much larger than expected from the compressibility effect and was found to be
      reversible. An equation derived from the dislocation theory that predicts the
      dependence of strength on the grain size and the shear modulus was used to
      interpret the strength data. The strength derived from the published grain size
      versus hardness data agreed well with the present results.

PMID- 22611107
TI  - Simultaneous determination of mean pressure and deviatoric stress based on
      numerical tensor analysis: a case study for polycrystalline x-ray diffraction of
      gold enclosed in a methanol-ethanol mixture.
AB  - It is known that the {100} and {111} planes of cubic crystals subjected to
      uniaxial deviatoric stress conditions have strain responses that are free from
      the effect of lattice preferred orientation. By utilizing this special character,
      one can unambiguously and simultaneously determine the mean pressure and
      deviatoric stress from polycrystalline diffraction data of the cubic sample. Here
      we introduce a numerical tensor calculation method based on the generalized
      Hooke's law to simultaneously determine the hydrostatic component of the stress
      (mean pressure) and deviatoric stress in the sample. The feasibility of this
      method has been tested by examining the experimental data of the Au pressure
      marker enclosed in a diamond anvil cell using a pressure medium of methanol
      ethanol mixture. The results demonstrated that the magnitude of the deviatoric
      stress is ~0.07 GPa at the mean pressure of 10.5 GPa, which is consistent with
      previous results of Au strength under high pressure. Our results also showed that
      even a small deviatoric stress (~0.07 GPa) could yield a ~0.3 GPa mean pressure
      error at ~10 GPa.

PMID- 22611108
TI  - Quantitative Rietveld texture analysis of CaSiO(3)  perovskite deformed in a
      diamond anvil cell.
AB  - The Rietveld method is used to extract quantitative texture information from a
      single synchrotron diffraction image of a CaSiO(3)  perovskite sample deformed in
      axial compression in a diamond anvil cell. The image used for analysis was taken
      in radial geometry at 49 GPa and room temperature. We obtain a preferred
      orientation of {100} lattice planes oriented perpendicular to the compression
      direction and this is compatible with [Formula: see text] slip.

PMID- 22611109
TI  - Advances in data reduction of high-pressure x-ray powder diffraction data from
      two-dimensional detectors: a case study of schafarzikite (FeSb(2)O(4)).
AB  - Methods have been developed to facilitate the data analysis of multiple two
      dimensional powder diffraction images. These include, among others, automatic
      detection and calibration of Debye-Scherrer ellipses using pattern recognition
      techniques, and signal filtering employing established statistical procedures
      like fractile statistics.All algorithms are implemented in the freely available
      program package Powder3D developed for the evaluation and graphical presentation
      of large powder diffraction data sets.As a case study, we report the pressure
      dependence of the crystal structure of iron antimony oxide FeSb(2)O(4) (p<=21
      GPa, T = 298 K) using high-resolution angle dispersive x-ray powder diffraction.
      FeSb(2)O(4) shows two phase transitions in the measured pressure range. The
      crystal structures of all modifications consist of frameworks of Fe(2+)O(6)
      octahedra and irregular Sb(3+)O(4) polyhedra. At ambient conditions, FeSb(2)O(4)
      crystallizes in space group P4(2)/mbc (phase I). Between p = 3.2 GPa and 4.1 GPa
      it exhibits a displacive second order phase transition to a structure of space
      group P 2(1)/c (phase II, a = 5.7792(4) A, b = 8.3134(9) A, c = 8.4545(11) A,
      beta = 91.879(10) degrees , at p = 4.2 GPa). A second phase transition occurs
      between p = 6.4 GPa and 7.4 GPa to a structure of space group P4(2)/m (phase III,
      a = 7.8498(4) A, c = 5.7452(5) A, at p = 10.5 GPa). A nonlinear compression
      behaviour over the entire pressure range is observed, which can be described by
      three Vinet equations in the ranges from p = 0.52 GPa to p = 3.12 GPa, p = 4.2
      GPa to p = 6.3 GPa and from p = 7.5 GPa to p = 19.8 GPa. The extrapolated bulk
      moduli of the high-pressure phases were determined to K(0) = 49(2) GPa for phase
      I, K(0) = 27(3) GPa for phase II and K(0) = 45(2) GPa for phase III. The crystal
      structures of all phases are refined against x-ray powder data measured at
      several pressures between p = 0.52 GPa, and 10.5 GPa. 

PMID- 22611110
TI  - Geometry and temperature effects of the interfacial thermal conductance in copper
      and nickel-graphene nanocomposites.
AB  - Graphene has excellent mechanical, electrical and thermal properties. Recently,
      graphene-metal composites have been proposed as a means to combine the properties
      of metals with those of graphene, leading to mechanically, electrically and
      thermally functional materials. The understanding of metal-graphene
      nanocomposites is of critical importance in developing next-generation
      electrical, thermal and energy devices, but we currently lack a fundamental
      understanding of how their geometry and composition control their thermal
      properties. Here we report a series of atomistic simulations, aimed at assessing
      the geometry and temperature effects of the thermal interface conductance for
      copper- and nickel-graphene nanocomposites. We find that copper-graphene and
      nickel-graphene nanocomposites have similar thermal interface conductances, but
      that both cases show a strong performance dependence on the number of graphene
      layers between metal phases. Single-graphene-layer nanocomposites have the
      highest thermal interface conductance, approaching ~500 MW m(-2) K(-1). The
      thermal interface conductance reduces to half this value in metal-bilayer
      graphene nanocomposites, and for more than three layers of graphene the thermal
      interface conductances further reduces to ~100 MW m(-2) K(-1) and becomes
      independent with respect to the number of layers of graphene. This dependence is
      attributed to the relatively stronger bonding between the metal and graphene
      layer, and relatively weaker bonding between graphene layers. Our results suggest
      that designs combining metal with single graphene layers provide the best thermal
      properties.

PMID- 22611111
TI  - Safety in numbers: anaphylaxis risk in childhood immunisation.

PMID- 22611112
TI  - Tocolysis with the beta-2-sympathomimetic hexoprenaline increases occurrence of
      infantile haemangioma in preterm infants.
AB  - BACKGROUND: Infantile haemangioma (IH) is the most commonly observed tumour in
      children. Off-label pharmacological treatment of IH with the beta-blocker
      propranolol induces regression of IH. Based on the fact that IH are more
      frequently observed in premature babies than in mature babies and the evidence
      that beta-blocker therapy leads to regression of IH, the authors generated the
      hypothesis that the use of beta-2-sympathomimetics during pregnancy for
      inhibiting premature labour might increase occurrence of IH in preterm infants.
      METHODS: For group comparison t test, Mann-Whitney U test and Fisher's exact test
      were used. Logistic regression was carried out by the forward stepwise method
      with Wald statistics. RESULTS: Data of 328 preterm infants (<32 gestational
      weeks) or with a birth weight of less than 1500 g (<36 gestational weeks) born
      between January 2006 and December 2008 were analysed. A total of 15 were excluded
      due do death within the 1st month of life, 38 because of lost to follow-up and
      six due to incomplete data. Complete data of 269 preterm infants were
      retrospectively analysed. During the follow-up period of median 1.6 years, 50
      infants developed one or more IH within their first 6 months of life. IH occurred
      in 40/181 patients with intrauterine exposure to the beta-2-sympathomimetic
      hexoprenaline and in 10/88 without exposure (OR=4.3; 95% CI 1.4 to 13.8).
      Furthermore, the influence of antenatal exposure to glucocorticosteroids for
      induction of lung development was analysed. Prenatally exposed subjects showed
      reduced occurrence of IH (OR=0.2; 95% CI 0.05 to 0.8). CONCLUSION: Intrauterine
      exposure to the beta-2-sympathomimetic hexoprenaline might increase the
      occurrence of IH in preterm infants.

PMID- 22611113
TI  - Pulse oximetry screening for congenital heart defects in newborn infants: an
      evaluation of acceptability to mothers.
AB  - BACKGROUND: Introducing neonatal screening procedures may not be readily accepted
      by parents and may increase anxiety. The acceptability of pulse oximetry
      screening to parents has not been previously reported. OBJECTIVE: To assess
      maternal acceptability of pulse oximetry screening for congenital heart defects
      and to identify factors predictive of participation in screening. DESIGN AND
      SETTING: A questionnaire was completed by a cross-sectional sample of mothers
      whose babies were recruited into the PulseOx Study which investigated the test
      accuracy of pulse oximetry screening. PARTICIPANTS: A total of 119 mothers of
      babies with false-positive (FP) results, 15 with true-positive and 679 with true
      negative results following screening. MAIN OUTCOME MEASURES: Questionnaires
      included measures of satisfaction with screening, anxiety, depression and
      perceptions of test results. RESULTS: Participants were predominantly satisfied
      with screening. The anxiety of mothers given FP results was not significantly
      higher than that of mothers given true-negative results (median score 32.7 vs
      30.0, p=0.09). White British/Irish mothers were more likely to participate in
      screening, with a decline rate of 5%; other ethnic groups were more likely to
      decline with the largest increase in declining being for Black African mothers
      (21%, OR 4.6, 95% CI 3.8 to 5.5). White British mothers were also less anxious
      (p<0.001) and more satisfied (p<0.001) than those of other ethnicities
      CONCLUSIONS: Pulse oximetry screening was acceptable to mothers and FP results
      were not found to increase anxiety. Factors leading to differences in
      participation and satisfaction across ethnic groups need to be identified so that
      staff can support parents appropriately.

PMID- 22611114
TI  - Aggressive posterior retinopathy of prematurity in large preterm babies in South
      India.
AB  - OBJECTIVE: To describe aggressive posterior retinopathy of prematurity (APROP) in
      a subset of premature babies, having gestational age (GA) of >=28 weeks and birth
      weight (BW) of >=1000 g. DESIGN: Retrospective observational case series. SETTING
      AND PATIENTS: Case records of 99 babies, who were diagnosed to have APROP between
      July 2002 and October 2010 were reviewed. Fundus fluorescein angiography (FFA)
      was carried out in 19 babies. RESULTS: The mean GA was 31.7 weeks (range 28-35
      weeks) and mean BW was 1572 g (range 1000-2310 g). All these babies received
      supplemental unblended oxygen 3 days or longer after birth. Of the 52 babies who
      had an eye exam in the neonatal intensive care unit prior to discharge, 35 babies
      had loss of vascularised retina from zone II to zone I and four babies from zone
      III to zone I, when examined as an outpatient. FFA revealed large geographic
      areas of vaso-obliteration (more than 30 disc areas) posterior to the shunt
      vessels within vascularised retina. CONCLUSIONS: Features of severe capillary bed
      loss in the vascularised retina were seen in our cases. Oxygen could be a
      precipitating factor in causing this retinopathy of prematurity in large babies.

PMID- 22611115
TI  - High variability and low irradiance of phototherapy devices in Dutch NICUs.
AB  - OBJECTIVE: To evaluate phototherapy practices by measuring the irradiance levels
      of phototherapy (PT) devices. DESIGN: Prospective study. SETTING: Tertiary
      neonatal intensive care units. PATIENTS: None. INTERVENTIONS: Irradiance levels
      of PT devices used in the 10 Dutch Neonatal Intensive Care Units (NICUs) were
      measured according to the local PT practice patterns. The irradiance levels of
      all overhead and fibre-optic PT devices were measured with a radiometer using an
      infant silhouette model. RESULTS: Eight different PT devices were used in the 10
      NICUs; five were overhead devices and three fibre-optic pads. The median (range)
      irradiance level for overhead PT devices was 9.7 (4.3-32.6) uW/cm(2)/nm and for
      fibre-optic pads 6.8 (0.8-15.6) uW/cm(2)/nm. Approximately 50% of PT devices
      failed to meet the minimal recommended irradiance level of 10 uW/cm(2)/nm.
      Maximal irradiance levels for overhead PT spot lights were inversely related to
      the distance between device and infant model (R2=0.33). The distances ranged from
      37 cm to 65 cm. CONCLUSIONS: PT devices in the Dutch NICUs show considerable
      variability with often too low irradiance levels. These results indicate that
      suboptimal PT is frequently applied and may even be ineffective towards reducing
      total serum bilirubin levels. These results underline the need for greater
      awareness among all healthcare workers towards the requirements for effective PT
      including measurements of irradiance and distance.

PMID- 22611117
TI  - An alternative drug (paracetamol) in the management of patent ductus arteriosus
      in ibuprofen-resistant or contraindicated preterm infants.

PMID- 22611116
TI  - Methods of weaning preterm babies <30 weeks gestation off CPAP: a multicentre
      randomised controlled trial.
AB  - BACKGROUND: Controversy exists whether different continuous positive airway
      pressure (CPAP) weaning methods influence time to wean off CPAP, CPAP duration,
      oxygen duration, Bronchopulmonary Dysplasia (BPD) or length of admission. AIMS:
      In a multicentre randomised controlled trial, the authors have primarily compared
      CPAP weaning methods impact on time to wean off CPAP and CPAP duration and
      secondarily their effect on oxygen duration, BPD and time of admission. METHODS:
      Between April 2006 and October 2009, 177 infants <30 weeks gestational age (GA)
      who fulfilled stability criteria on CPAP were randomised to one of the three CPAP
      weaning methods (M). M1: Taken 'OFF' CPAP with the view to stay 'OFF'. M2: Cycled
      on and off CPAP with incremental time 'OFF'. M3: As with m(2), cycled on and off
      CPAP but during 'OFF' periods were supported by 2 mm nasal cannula at a flow of
      0.5 l/min. RESULTS: Based on intention to treat analysis, there was no
      significant difference in mean GA or birthweight between the groups (27.1 +/-
      1.4, 26.9 +/- 1.6 and 27.3 +/- 1.5 (weeks +/- 1SD) and 988 +/- 247, 987 +/- 249
      and 1015 +/- 257 (grams +/- 1SD), respectively). Primary outcomes showed M1
      produced a significantly shorter time to wean from CPAP (11.3 +/- 0.8, 16.8 +/-
      1.0, 19.4 +/- 1.3 (days +/- 1SE) p<0.0001, respectively) and CPAP duration (24.4
      +/- 0.1, 38.6 +/- 0.1, 30.5 +/- 0.1 (days +/- 1SE) p<0.0001, respectively). All
      the secondary outcomes were significantly shorter with M1, (oxygen duration: 24.1
      +/- 1.5, 45.8 +/- 2.2, 34.1 +/- 2.0 (days +/- 1SE) p<0.0001, BPD: 7/56 (12.5%),
      29/69 (42%), 10/52 (19%) p=0.011 and length of admission: 58.5 +/- 0.1, 73.8 +/-
      0.1 69.5 +/- 0.1 (days +/- 1SE) p<0.0001, respectively). CONCLUSION: Method 1
      significantly shortens CPAP weaning time, CPAP duration, oxygen duration, BPD and
      admission time.

PMID- 22611118
TI  - Fetal surgery for neural tube defects.

PMID- 22611119
TI  - Machine learning approaches for the discovery of gene-gene interactions in
      disease data.
AB  - Because of the complexity of gene-phenotype relationships machine learning
      approaches have considerable appeal as a strategy for modelling interactions. A
      number of such methods have been developed and applied in recent years with some
      modest success. Progress is hampered by the challenges presented by the
      complexity of the disease genetic data, including phenotypic and genetic
      heterogeneity, polygenic forms of inheritance and variable penetrance, combined
      with the analytical and computational issues arising from the enormous number of
      potential interactions. We review here recent and current approaches focusing,
      wherever possible, on applications to real data (particularly in the context of
      genome-wide association studies) and looking ahead to the further challenges
      posed by next generation sequencing data.

PMID- 22611120
TI  - Mass spectrometry of apolipoprotein C-III, a simple analytical method for mucin
      type O-glycosylation and its application to an autosomal recessive cutis laxa
      type-2 (ARCL2) patient.
AB  - Apolipoprotein C-III (apoCIII) is a small glycoprotein with a single mucin-type
      core-1 oligosaccharide and is analyzed by isoelectric focusing (IEF) for the
      diagnosis of genetic defects in O-glycan biosynthesis such as congenital
      disorders of glycosylation. In the present study, mass spectrometry of apoCIII,
      after a simple procedure for sample preparation using a small amount of serum,
      was demonstrated to be a reliable alternative to IEF. It allows reproducible
      glycan profiling and detection of unglycosylated species. This method was applied
      to an autosomal recessive cutis laxa type-2 patient and demonstrated decreased
      site occupancy by O-glycosylation.

PMID- 22611122
TI  - What I've learned from BMJ case reports: pains in the neck.

PMID- 22611123
TI  - Improving communication with adolescents.
AB  - Communication with young people (YP) can be problematic. However, effective
      communication can improve health outcomes and there is randomised clinical trial
      level evidence that communication skills can be learnt. Key issues when
      communicating with YP: (1) The young person should be central in the
      communication, with discussions primarily focused on him/her; (2) The young
      person should be offered time alone with the clinician; (3) Conditional
      confidentiality should be discussed, and does not reduce rates of disclosure; (4)
      Ambivalence is normal--techniques can be learnt to help the young person resolve
      ambivalence and change behaviour; (5) A psychosocial history is a key part of the
      adolescent consultation, and should include resilience factors as well as risk.
      We also discuss pragmatic techniques to use in busy consultations to improve
      communication and promote behaviour change in YP.

PMID- 22611124
TI  - Assessment of childhood obesity in secondary care: OSCA consensus statement.
AB  - This expert opinion provides detailed guidance on assessing obesity in secondary
      paediatric practice. This guidance builds on existing recommendations from
      National Institute of Health and Clinical Excellence in the UK, and is evidence
      based where possible. Guidance is provided on which obese children and young
      people are appropriate to be seen in secondary care and relevant history and
      investigations, and guidance on when further investigation of causes and obesity
      related comorbidity is appropriate.

PMID- 22611125
TI  - From menorrhagia to manometers.
AB  - We present a case that illustrates the challenges in making a unifying diagnosis
      and bringing together symptoms which, at first, seem unrelated. We aim to
      illustrate the process of decision-making and the practice of working along
      several parallel processes to reach a single explanation for a child to present
      unwell.

PMID- 22611126
TI  - What I learned from DTB: acute infective conjunctivitis?

PMID- 22611128
TI  - Mucin 21 in esophageal squamous epithelia and carcinomas: analysis with glycoform
      specific monoclonal antibodies.
AB  - Monoclonal antibodies (mAbs) against mucin 21 (MUC21), a human counterpart of
      mouse epiglycanin/Muc21, were prepared using human embryonic kidney 293 cells
      transfected with MUC21 as the immunogen. The specificity of these mAbs was
      examined by flow cytometry, immunoprecipitation and western blotting focusing on
      the differential glycosylation of MUC21 expressed in variant Chinese hamster
      ovary (CHO) cells (ldlD cells and Lec2 cells) and CHO-K1 cells. One of these
      mAbs, heM21D, bound to both the unmodified core polypeptide of MUC21 and MUC21
      attached with N-acetylgalactosamine (Tn-MUC21). Six antibodies, including mAb
      heM21C, bound to MUC21 with Tn, T or sialyl-T epitopes but not the unmodified
      core polypeptide of MUC21. Esophageal squamous carcinomas and adjacent squamous
      epithelia were immunohistochemically examined for the binding of these mAbs.
      MUC21 was expressed in esophageal squamous epithelial cells, and its O-glycan
      extended forms were observed in the luminal portions of squamous epithelia. As
      revealed by the binding of mAb heM21D and the absence of reactivity with mAb
      heM21C, esophageal squamous carcinoma cells produce MUC21 without the attachment
      of O-glycans. This is the first report to show that there is a change in the
      glycoform of MUC21 that can be used to differentiate between squamous epithelia
      and squamous carcinoma of the esophagus. Thus, these antibodies represent a
      useful tool to characterize squamous epithelial differentiation and
      carcinogenesis.

PMID- 22611129
TI  - Efficient RNA pairwise structure comparison by SETTER method.
AB  - MOTIVATION: Understanding the architecture and function of RNA molecules requires
      methods for comparing and analyzing their 3D structures. Although a structural
      alignment of short RNAs is achievable in a reasonable amount of time, large
      structures represent much bigger challenge. However, the growth of the number of
      large RNAs deposited in the PDB database calls for the development of fast and
      accurate methods for analyzing their structures, as well as for rapid similarity
      searches in databases. RESULTS: In this article a novel algorithm for an RNA
      structural comparison SETTER (SEcondary sTructure-based TERtiary Structure
      Similarity Algorithm) is introduced. SETTER uses a pairwise comparison method
      based on 3D similarity of the so-called generalized secondary structure units.
      For each pair of structures, SETTER produces a distance score and an indication
      of its statistical significance. SETTER can be used both for the structural
      alignments of structures that are already known to be homologous, as well as for
      3D structure similarity searches and functional annotation. The algorithm
      presented is both accurate and fast and does not impose limits on the size of
      aligned RNA structures. AVAILABILITY: The SETTER program, as well as all
      datasets, is freely available from http://siret.cz/hoksza/projects/setter/.

PMID- 22611131
TI  - Gossamer--a resource-efficient de novo assembler.
AB  - MOTIVATION: The de novo assembly of short read high-throughput sequencing data
      poses significant computational challenges. The volume of data is huge; the reads
      are tiny compared to the underlying sequence, and there are significant numbers
      of sequencing errors. There are numerous software packages that allow users to
      assemble short reads, but most are either limited to relatively small genomes
      (e.g. bacteria) or require large computing infrastructure or employ greedy
      algorithms and thus often do not yield high-quality results. RESULTS: We have
      developed Gossamer, an implementation of the de Bruijn approach to assembly that
      requires close to the theoretical minimum of memory, but still allows efficient
      processing. Our results show that it is space efficient and produces high-quality
      assemblies. AVAILABILITY: Gossamer is available for non-commercial use from
      http://www.genomics.csse.unimelb.edu.au/product-gossamer.php.

PMID- 22611130
TI  - regSNPs: a strategy for prioritizing regulatory single nucleotide substitutions.
AB  - MOTIVATION: One of the fundamental questions in genetics study is to identify
      functional DNA variants that are responsible to a disease or phenotype of
      interest. Results from large-scale genetics studies, such as genome-wide
      association studies (GWAS), and the availability of high-throughput sequencing
      technologies provide opportunities in identifying causal variants. Despite the
      technical advances, informatics methodologies need to be developed to prioritize
      thousands of variants for potential causative effects. RESULTS: We present
      regSNPs, an informatics strategy that integrates several established
      bioinformatics tools, for prioritizing regulatory SNPs, i.e. the SNPs in the
      promoter regions that potentially affect phenotype through changing transcription
      of downstream genes. Comparing to existing tools, regSNPs has two distinct
      features. It considers degenerative features of binding motifs by calculating the
      differences on the binding affinity caused by the candidate variants and
      integrates potential phenotypic effects of various transcription factors. When
      tested by using the disease-causing variants documented in the Human Gene
      Mutation Database, regSNPs showed mixed performance on various diseases. regSNPs
      predicted three SNPs that can potentially affect bone density in a region
      detected in an earlier linkage study. Potential effects of one of the variants
      were validated using luciferase reporter assay.

PMID- 22611132
TI  - PyKnot: a PyMOL tool for the discovery and analysis of knots in proteins.
AB  - SUMMARY: Understanding the differences between knotted and unknotted protein
      structures may offer insights into how proteins fold. To characterize the type of
      knot in a protein, we have developed PyKnot, a plugin that works seamlessly
      within the PyMOL molecular viewer and gives quick results including the knot's
      invariants, crossing numbers and simplified knot projections and backbones.
      PyKnot may be useful to researchers interested in classifying knots in
      macromolecules and provides tools for students of biology and chemistry with
      which to learn topology and macromolecular visualization. AVAILABILITY: PyMOL is
      available at http://www.pymol.org. The PyKnot module and tutorial videos are
      available at http://youtu.be/p95aif6xqcM. CONTACT: rhonald.lua@gmail.com.

PMID- 22611133
TI  - Tailored therapy for heart failure: the role of biomarkers.

PMID- 22611134
TI  - Completely occluded aorta associated with coronary heart disease.

PMID- 22611135
TI  - Cholesterol pericarditis with massive pericardial cholesterol cyst.

PMID- 22611137
TI  - A comparison of several methods of macular hole measurement using optical
      coherence tomography, and their value in predicting anatomical and visual
      outcomes.
AB  - BACKGROUND/AIMS: To compare several methods of macular hole measurement using
      optical coherence tomography (OCT), and to assess their predictive capability
      against anatomical and visual outcomes in a single cohort of patients. METHODS: A
      retrospective study of 50 eyes undergoing standardised macular hole surgery. All
      patients underwent preoperative OCT scanning with measurement of macular hole
      inner opening diameter, minimum linear diameter, base diameter and macular hole
      height. Values were calculated for the macular hole index and the tractional hole
      index. RESULTS: Logistic regression analyses indicated that the preoperative base
      diameter, macular hole inner opening and minimum linear diameter were associated
      with both anatomical and visual success. Derived parameters as alternatives to
      these basic ophthalmic parameters add little to the modelling of either
      anatomical or visual success. CONCLUSION: Base diameter, macular hole inner
      opening and minimum linear diameter can each be used to predict anatomical and/or
      functional success in macular hole surgery. Preoperative base diameter is the
      most useful variable in this regard, as it holds the strongest association with
      anatomical and visual outcome and is easily measured on a OCT scan.

PMID- 22611138
TI  - Experience of intra-arterial chemosurgery with single agent carboplatin for
      retinoblastoma.

PMID- 22611136
TI  - ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure
      2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart
      Failure 2012 of the European Society of Cardiology. Developed in collaboration
      with the Heart Failure Association (HFA) of the ESC.

PMID- 22611139
TI  - The effect of gravitational force on limbal stem cell growth.
AB  - AIM: To evaluate the effect of gravity on corneal epithelial cell migration in
      vitro. METHODS: Fourteen donor peripheral corneoscleral rims were used. Twenty
      explants were chosen of which 10 were placed vertically and 10 were placed
      horizontally during culture. Analyses were performed to investigate the effect of
      gravity on epithelial growth by measuring the extent of epithelial cell growth
      above and below the horizontal meridian and counting the total number of cells
      using a haemocytometer. RESULTS: There was no statistically significant
      difference in cell growth between the explants that were placed horizontally and
      vertically. However, in the vertical explant group the cells grew preferentially
      towards the 6 o'clock direction, possibly as a result of gravity. CONCLUSIONS:
      Gravitational forces may influence cell migration in vitro. This could be of
      significance in the planning of limbal transplantation, because a superior graft
      may be more likely to succeed than a gravitationally challenged inferior graft.

PMID- 22611140
TI  - Sports injuries and illnesses during the second Asian Beach Games.
AB  - BACKGROUND: Prevention of sport injuries and illnesses is a focus for
      epidemiological surveillance. OBJECTIVES: To record and analyse all sports
      injuries and illnesses registered during the second Asian Beach Games. DESIGN: A
      descriptive epidemiological study using the International Olympic Committee
      Surveillance system to register injuries and illnesses during the second Asian
      Beach Games. METHODS: The second Asian Beach Games hosted 1132 athletes from 43
      countries competing in 14 beach sports. All National Olympic Committees'
      physicians of the participating teams were invited to report all injuries and
      illnesses. In addition, medical officers at the different Olympic venues and the
      main Olympic village reported injuries and illnesses treated at the clinics on a
      daily basis. RESULTS: A total of 177 injuries were reported equating to an
      incidence rate of 156.4 per 1000 registered athletes. Tent pegging recorded the
      highest incidence of injuries with 357 per 1000 registered athletes. The most
      prevalent injuries were in the foot/toe with 14.1% of all reported injuries. The
      majority of injuries were incurred during competition (75.4%). In addition, the
      most common mechanism of injury was contact with another athlete (n=42, 23.7%)
      and combined sudden and gradual overuse contributed to 30% of the total injury
      burden. Furthermore, 118 illnesses were reported resulting in an incidence rate
      of 104.2 illnesses per 1000 registered athletes. The most affected system was the
      respiratory tract (39.1%) with infection being the most common cause (n=33,
      38.0%). The incidence of injury and illness differed significantly among the 14
      sports. CONCLUSION: The data indicate that the risk of injury from beach games is
      sport dependant. This means that any preventive measures have to be tailored for
      each discipline. Furthermore, the study showed that respiratory infections are
      the commonest illness in beach sports and therefore, event organisers should
      focus improving public health measures and hygiene awareness.

PMID- 22611141
TI  - A giant coronary aneurysm associated with a fractured cobalt-chromium stent.

PMID- 22611143
TI  - Pneumonectomy for benign disease: analysis of the early and late outcomes.
AB  - OBJECTIVES: To analyse the indications, operative techniques, postoperative
      morbidity, mortality and long-term outcomes of patients who underwent
      pneumonectomy for benign lung disease. METHODS: We retrospectively reviewed our
      institutional database for patients who underwent a pneumonectomy for benign lung
      disease from January 1991 to June 2010. The data were queried for the indications
      for surgery, details of operative technique, development of perioperative
      complications, mortality and long-term survival. RESULTS: There were 32 patients,
      19 men (59%) and 13 women, with a mean age of 48 years (17-78). Indications for
      pneumonectomy included pulmonary tuberculosis in 10 patients (31%), chronic
      septic lung disease in seven (22%), invasive opportunistic infections in five
      (16%), fibrosing mediastinitis in four (12%) and other in six (19%).
      Pneumonectomies were left-sided in 17 (53%) and right-sided in 15 patients; nine
      (28%) were completion pneumonectomies. Intraoperatively, intrapericardial
      isolation was performed in 21 (66%) patients and extrapleural dissection in seven
      (22%); bronchial reinforcement was performed in 25 (78%). Operative mortality
      occurred in two (6%) patients. Major complications occurred in 12 (38%) patients;
      no patient developed bronchopleural fistula or postpneumonectomy empyema
      requiring intervention. Overall 5-year survival was 75% (95% CI 56.2-87.9), with
      a mean follow-up of 99 months. CONCLUSIONS: Pneumonectomy for benign disease is a
      high-risk procedure performed for a variety of indications. A detailed operative
      technique is of the utmost importance to minimize postoperative morbidity and
      mortality. Despite an increased perioperative risk, the long-term outcomes can be
      especially satisfactory. Pneumonectomy for benign disease should continue to be a
      treatment option for carefully selected patients.

PMID- 22611144
TI  - Which management strategy should be chosen for calcified masses of the mitral
      annulus?

PMID- 22611145
TI  - Minimally invasive mitral valve surgery is a very safe procedure with very low
      rates of conversion to full sternotomy.
AB  - OBJECTIVES: Over the past 10 years, minimally invasive mitral valve surgery (MI
      MVS) has become the standard approach for treatment of atrio-ventricular valve
      disease in specialized centres. This approach uses a right lateral mini
      thoracotomy and femoral cannulation for cardiopulmonary bypass. In a very low
      number of patients, conversion to full sternotomy may be necessary. METHODS: A
      total of 3125 patients underwent MI-MVS between 1999 and 2010 at our institution.
      Conversion to full sternotomy was required in 1.0% (n=34) of all patients.
      Patient data, including intraoperative course and postoperative outcome, were
      collected. Follow-up data were collected in a prospective database and analysed
      retrospectively. RESULTS: A total of 34 patients underwent conversion to full
      sternotomy during MI-MVS. The mean age of patients was 67.9+/-9.5 years, and 17
      patients were female (50%). The main reasons for conversion were as follows:
      major bleeding in 18 patients (52.9%); severe pulmonary adhesions in six patients
      (17.6%); and aortic dissection in five patients (14.7%). The clinical outcome of
      these patients was impaired, with the development of acute renal failure in 13
      patients (38.2%) and respiratory failure in 10 patients (29.4%). Operative
      mortality (30 days) was 23.5% (eight patients). The reason for death in all these
      patients was low cardiac output syndrome with subsequent multi-organ failure.
      CONCLUSIONS: This large series shows that MI-MVS can be performed with very low
      complication rates. In the experience of this large single-centre study,
      conversion to full sternotomy was necessary in only 1% of all patients. If
      conversion is indicated, however, it is associated with a high operative
      mortality.

PMID- 22611146
TI  - Sickle cell trait: what's a sports medicine clinician to think?

PMID- 22611147
TI  - BokSmart - implementing a National Rugby Safety Programme.

PMID- 22611148
TI  - Pathophysiology of exertional death associated with sickle cell trait: can we
      make a parallel with vaso-occlusion mechanisms in sickle cell disease?

PMID- 22611150
TI  - Long-term outcomes after autologous stem cell transplantation for patients with
      POEMS syndrome (osteosclerotic myeloma): a single-center experience.
AB  - The POEMS syndrome (polyradiculoneuropathy, organomegaly, multiple
      endocrinopathies, monoclonal protein, skin changes) is a rare disease associated
      with a plasma cell dyscrasia. Patients with disseminated POEMS can be treated
      with high-dose therapy and autologous stem cell transplantation (ASCT). While
      clinical improvement is nearly universal in these patients, the long-term
      outcomes after transplantation are unclear. We therefore assessed the long-term
      clinical outcomes of 59 POEMS patients treated with ASCT at our institution. With
      a median follow-up of 45 months, 14 patients have progressed with a progression
      free survival of 98% and 75% at 1 and 5 years, respectively. Factors associated
      with progression have included an IgG-lambda monoclonal component (hazard ratio
      [HR] 7.5; 95% confidence interval [CI], 2.3-28.3; P = .0008), fluorodeoxyglucose
      avid lesions on baseline positron emission tomography (HR 6.4; 95% CI, 1.2-120; P
      = .03), lack of complete hematologic response (HR 5.4; 95% CI, 1.8-16.7; P =
      .003), and patients aged 50 years or younger at transplantation (HR 4.4; 95% CI,
      1.3-20; P = .01). The most common progression events have been radiologic
      followed by rising VEGF. Symptomatic progression has been rare. Most patients
      could be salvaged with immunomodulatory drugs or radiation. The 5-year survival
      is 94%. Herein, we describe a system of monitoring response and progression among
      patients with POEMS after ASCT.

PMID- 22611152
TI  - Pivotal role of plasmacytoid dendritic cells in inflammation and NK-cell
      responses after TLR9 triggering in mice.
AB  - The physiologic role played by plasmacytoid dendritic cells (pDCs) in the
      induction of innate responses and inflammation in response to pathogen signaling
      is not well understood. Here, we describe a new mouse model lacking pDCs and
      establish that pDCs are essential for the in vivo induction of NK-cell activity
      in response to Toll-like receptor 9 (TLR9) triggering. Furthermore, we provide
      the first evidence that pDCs are critical for the systemic production of a wide
      variety of chemokines in response to TLR9 activation. Consequently, we observed a
      profound alteration in monocyte, macrophage, neutrophil, and NK-cell recruitment
      at the site of inflammation in the absence of pDCs in response to CpG-Dotap and
      stimulation by microbial pathogens, such as Leishmania major, Escherichia coli,
      and Mycobacterium bovis. This study, which is based on the development of a
      constitutively pDC-deficient mouse model, highlights the pivotal role played by
      pDCs in the induction of innate immune responses and inflammation after TLR9
      triggering.

PMID- 22611151
TI  - Critical role of P1-Runx1 in mouse basophil development.
AB  - Runx1(P1N/P1N) mice are deficient in the transcription factor distal promoter
      derived Runt-related transcription factor 1 (P1-Runx1) and have a > 90% reduction
      in the numbers of basophils in the BM, spleen, and blood. In contrast,
      Runx1(P1N/P1N) mice have normal numbers of the other granulocytes (neutrophils
      and eosinophils). Although basophils and mast cells share some common features,
      Runx1(P1N/P1N) mice have normal numbers of mast cells in multiple tissues.
      Runx1(P1N/P1N) mice fail to develop a basophil-dependent reaction, IgE-mediated
      chronic allergic inflammation of the skin, but respond normally when tested for
      IgE- and mast cell-dependent passive cutaneous anaphylaxis in vivo or IgE
      dependent mast cell degranulation in vitro. These results demonstrate that
      Runx1(P1N/P1N) mice exhibit markedly impaired function of basophils, but not mast
      cells. Infection with the parasite Strongyloides venezuelensis and injections of
      IL-3, each of which induces marked basophilia in wild-type mice, also induce
      modest expansions of the very small populations of basophils in Runx1(P1N/P1N)
      mice. Finally, Runx1(P1N/P1N) mice have normal numbers of the granulocyte
      progenitor cells, SN-Flk2(+/-), which can give rise to all granulocytes, but
      exhibit a > 95% reduction in basophil progenitors. The results of the present
      study suggest that P1-Runx1 is critical for a stage of basophil development
      between SN-Flk2(+/-) cells and basophil progenitors.

PMID- 22611154
TI  - Circulating DNA and myeloperoxidase indicate disease activity in patients with
      thrombotic microangiopathies.
AB  - Thrombotic microangiopathies (TMAs) are a group of life-threatening disorders
      characterized by thrombocytopenia, fragmentation of erythrocytes, and ischemic
      organ damage. Genetic disorders, autoimmune disease, and cancer are risk factors
      for TMAs, but an additional, unknown trigger is needed to bring about acute
      disease. Recent studies suggest that DNA and histones are released during
      inflammation or infection and stimulate coagulation, thrombosis,
      thrombocytopenia, and organ damage in mice. We show that extracellular DNA and
      histones as well as markers of neutrophils are present in acute TMAs. Analysis of
      plasma from TMA patients of different clinical categories revealed elevated
      levels of DNA-histone complexes and myeloperoxidase (MPO) from neutrophil
      granules as well as S100A8/A9, a heterocomplex abundant in neutrophil cytosol.
      During therapy of thrombotic thrombocytopenic purpura, a subtype of TMAs often
      associated with severe ADAMTS13 (a disintegrin and metalloproteinase with
      thrombospondin type 1 motifs, member 13) deficiency, plasma DNA and MPO were
      inversely correlated with platelet counts, and their levels indicated
      amelioration or exacerbation of the disease. ADAMTS13 deficiency together with
      increased levels of plasma DNA and MPO were characteristic for acute thrombotic
      thrombocytopenic purpura. A minor infection often precedes acute TMA and
      extracellular DNA and histones released during the inflammatory response could
      provide the second hit, which precipitates acute TMA in patients with pre
      existing risk factors.

PMID- 22611153
TI  - SLC35D3 delivery from megakaryocyte early endosomes is required for platelet
      dense granule biogenesis and is differentially defective in Hermansky-Pudlak
      syndrome models.
AB  - Platelet dense granules are members of a family of tissue-specific, lysosome
      related organelles that also includes melanosomes in melanocytes. Contents
      released from dense granules after platelet activation promote coagulation and
      hemostasis, and dense granule defects such as those seen in Hermansky-Pudlak
      syndrome (HPS) cause excessive bleeding, but little is known about how dense
      granules form in megakaryocytes (MKs). In the present study, we used SLC35D3,
      mutation of which causes a dense granule defect in mice, to show that early
      endosomes play a direct role in dense granule biogenesis. We show that SLC35D3
      expression is up-regulated during mouse MK differentiation and is enriched in
      platelets. Using immunofluorescence and immunoelectron microscopy and subcellular
      fractionation in megakaryocytoid cells, we show that epitope-tagged and
      endogenous SLC35D3 localize predominantly to early endosomes but not to dense
      granule precursors. Nevertheless, SLC35D3 is depleted in mouse platelets from 2
      of 3 HPS models and, when expressed ectopically in melanocytes, SLC35D3 localizes
      to melanosomes in a manner requiring a HPS-associated protein complex that
      functions from early endosomal transport intermediates. We conclude that SLC35D3
      is either delivered to nascent dense granules from contiguous early endosomes as
      MKs mature or functions in dense granule biogenesis directly from early
      endosomes, suggesting that dense granules originate from early endosomes in MKs.

PMID- 22611155
TI  - How I treat polycythemia vera.
AB  - Polycythemia vera (PV) is a clonal disorder characterized by unwarranted
      production of red blood cells. In the majority of cases, PV is driven by
      oncogenic mutations that constitutively activate the JAK-STAT signal transduction
      pathway, such as JAK2 V617F, or exon 12 mutations or LNK mutations. Diagnosis of
      PV is based on the WHO criteria. Diagnosis of post-PV myelofibrosis is
      established according to the International Working Group for Myeloproliferative
      Neoplasms Research and Treatment criteria. Different clinical presentations of PV
      are discussed. Prognostication of PV is tailored to the most frequent
      complication during follow-up, namely, thrombosis. Age older than 60 years and
      prior history of thrombosis are the 2 main risk factors for disease
      stratification. Correlations are emerging between leukocytosis, JAK2(V617F)
      mutation, BM fibrosis, and different outcomes of PV, which need to be confirmed
      in prospective studies. In my practice, hydroxyurea is still the "gold standard"
      when cytoreduction is needed, even though pegylated IFN-alfa-2a and ruxolitinib
      might be useful in particular settings. Results of phase 1 or 2 studies
      concerning these latter agents should however be confirmed by the ongoing
      randomized phase 3 clinical trials. In this paper, I discuss the main problems
      encountered in daily clinical practice with PV patients regarding diagnosis,
      prognostication, and therapy.

PMID- 22611156
TI  - Treatment of erythropoietin deficiency in mice with systemically administered
      siRNA.
AB  - Anemia linked to a relative deficiency of renal erythropoietin production is a
      significant cause of morbidity and medical expenditures in the developed world.
      Recombinant erythropoietin is expensive and has been linked to excess
      cardiovascular events. Moreover, some patients become refractory to
      erythropoietin because of increased production of factors such as hepcidin.
      During fetal life, the liver, rather than the kidney, is the major source of
      erythropoietin. In the present study, we show that it is feasible to reactivate
      hepatic erythropoietin production and suppress hepcidin levels using systemically
      delivered siRNAs targeting the EglN prolyl hydroxylases specifically in the
      liver, leading to improved RBC production in models of anemia caused by either
      renal insufficiency or chronic inflammation with enhanced hepcidin production.

PMID- 22611157
TI  - Induction of activin B by inflammatory stimuli up-regulates expression of the
      iron-regulatory peptide hepcidin through Smad1/5/8 signaling.
AB  - Anemia is very common in patients suffering from infections or chronic
      inflammation and can add substantially to the morbidity of the underlying
      disease. It is mediated by excessive production of the iron-regulatory peptide
      hepcidin, but the signaling pathway responsible for hepcidin up-regulation in the
      inflammatory context is still not understood completely. In the present study, we
      show that activin B has an unexpected but crucial role in the induction of
      hepcidin by inflammation. There is a dramatic induction of Inhbb mRNA, encoding
      the activin beta(B)-subunit, in the livers of mice challenged with
      lipopolysaccharide, slightly preceding an increase in Smad1/5/8 phosphorylation
      and Hamp mRNA. Activin B also induces Smad1/5/8 phosphorylation in human hepatoma
      derived cells and, synergistically with IL-6 and STAT-3 signaling, up-regulates
      hepcidin expression markedly, an observation confirmed in mouse primary
      hepatocytes. Pretreatment with a bone morphogenic protein type I receptor
      inhibitor showed that the effect of activin B on hepcidin expression is entirely
      attributable to its effect on bone morphogenetic protein signaling, most likely
      via activin receptor-like kinase 3. Activin B is therefore a novel and specific
      target for the treatment of anemia of inflammation.

PMID- 22611158
TI  - APELIN promotes hematopoiesis from human embryonic stem cells.
AB  - Transcriptional profiling of differentiating human embryonic stem cells (hESCs)
      revealed that MIXL1-positive mesodermal precursors were enriched for transcripts
      encoding the G-protein-coupled APELIN receptor (APLNR). APLNR-positive cells,
      identified by binding of the fluoresceinated peptide ligand, APELIN (APLN), or an
      anti-APLNR mAb, were found in both posterior mesoderm and anterior mesendoderm
      populations and were enriched in hemangioblast colony-forming cells (Bl-CFC). The
      addition of APLN peptide to the media enhanced the growth of embryoid bodies
      (EBs), increased the expression of hematoendothelial genes in differentiating
      hESCs, and increased the frequency of Bl-CFCs by up to 10-fold. Furthermore, APLN
      peptide also synergized with VEGF to promote the growth of hESC-derived
      endothelial cells. These studies identified APLN as a novel growth factor for
      hESC-derived hematopoietic and endothelial cells.

PMID- 22611159
TI  - NFAT control of innate immunity.
AB  - The calcineurin/nuclear factor of activated T cells (NFAT) signaling pathway
      mediates multiple adaptive T-cell functions, but recent studies have shown that
      calcineurin/NFAT signaling also contributes to innate immunity and regulates the
      homeostasis of innate cells. Myeloid cells, including granulocytes and dendritic
      cells, can promote inflammation, regulate adaptive immunity, and are essential
      mediators of early responses to pathogens. Microbial ligation of pattern
      recognition receptors, such as TLR4, CD14, and dectin 1, is now known to induce
      the activation of calcineurin/NFAT signaling in myeloid cells, a finding that has
      provided new insights into the molecular pathways that regulate host protection.
      Inhibitors of calcineurin/NFAT binding, such as cyclosporine A and FK506, are
      broadly used in organ transplantation and can act as potent immunosuppressive
      drugs in a variety of different disorders. There is increasing evidence that
      these agents influence innate responses as well as inhibiting adaptive T-cell
      functions. This review focuses on the role of calcineurin/NFAT signaling in
      myeloid cells, which may contribute to the various unexplained effects of
      immunosuppressive drugs already being used in the clinic.

PMID- 22611160
TI  - Brentuximab vedotin enables successful reduced-intensity allogeneic hematopoietic
      cell transplantation in patients with relapsed or refractory Hodgkin lymphoma.
AB  - Brentuximab vedotin induces an overall response rate of 75% in patients with
      relapsed/refractory Hodgkin lymphoma, but its impact on future allogeneic
      transplantation (allo-HCT) is not known. We retrospectively examined the records
      of 18 patients with relapsed/refractory Hodgkin lymphoma who were treated on
      brentuximab vedotin clinical trials to evaluate the efficacy and safety of
      subsequent reduced-intensity allo-HCT. Seventeen patients had previous autologous
      transplant; 6 were in complete remission, and 8 were in partial remission before
      allo-HCT with 12 grafts from unrelated or mismatched donors. The 1-year overall
      survival was 100%, progression-free survival was 92.3%, and nonrelapse mortality
      was 0% (median follow-up, 14 months). The incidence of acute GVHD was 27.8% and
      chronic GVHD was 56.3%. Brentuximab vedotin before reduced-intensity allo-HCT
      does not appear to adversely affect engraftment, GVHD, or survival and may
      provide sufficient disease control to enable reduced-intensity allo-HCT.

PMID- 22611161
TI  - On the role of FAN1 in Fanconi anemia.
AB  - Fanconi anemia (FA) is a rare bone marrow failure disorder with defective DNA
      interstrand crosslink repair. Still, there are FA patients without mutations in
      any of the 15 genes individually underlying the disease. A candidate protein for
      those patients, FA nuclease 1 (FAN1), whose gene is located at chromosome
      15q13.3, is recruited to stalled replication forks by binding to
      monoubiquitinated FANCD2 and is required for interstrand crosslink repair,
      suggesting that mutation of FAN1 may cause FA. Here we studied clinical,
      cellular, and genetic features in 4 patients carrying a homozygous 15q13.3 micro
      deletion, including FAN1 and 6 additional genes. Biallelic deletion of the entire
      FAN1 gene was confirmed by failure of 3'- and 5'-PCR amplification. Western blot
      analysis failed to show FAN1 protein in the patients' cell lines. Chromosome
      fragility was normal in all 4 FAN1-deficient patients, although their cells
      showed mild sensitivity to mitomycin C in terms of cell survival and G(2) phase
      arrest, dissimilar in degree to FA cells. Clinically, there were no symptoms
      pointing the way to FA. Our results suggest that FAN1 has a minor role in
      interstrand crosslink repair compared with true FA genes and exclude FAN1 as a
      novel FA gene.

PMID- 22611162
TI  - Inhibition of tau aggregation in a novel Caenorhabditis elegans model of
      tauopathy mitigates proteotoxicity.
AB  - Increased Tau protein amyloidogenicity has been causatively implicated in several
      neurodegenerative diseases, collectively called tauopathies. In pathological
      conditions, Tau becomes hyperphosphorylated and forms intracellular aggregates.
      The deletion of K280, which is a mutation that commonly appears in patients with
      frontotemporal dementia with Parkinsonism linked to chromosome 17, enhances Tau
      aggregation propensity (pro-aggregation). In contrast, introduction of the I277P
      and I308P mutations prevents beta-sheet formation and subsequent aggregation
      (anti-aggregation). In this study, we created a tauopathy model by expressing pro
      or anti-aggregant Tau species in the nervous system of Caenorhabditis elegans.
      Animals expressing the highly amyloidogenic Tau species showed accelerated Tau
      aggregation and pathology manifested by severely impaired motility and evident
      neuronal dysfunction. In addition, we observed that the axonal transport of
      mitochondria was perturbed in these animals. Control animals expressing the anti
      aggregant combination had rather mild phenotype. We subsequently tested several
      Tau aggregation inhibitor compounds and observed a mitigation of Tau
      proteotoxicity. In particular, a novel compound that crosses the blood-brain
      barrier of mammals proved effective in ameliorating the motility as well as
      delaying the accumulation of neuronal defects. Our study establishes a new C.
      elegans model of Tau aggregation-mediated toxicity and supports the emerging
      notion that inhibiting the nucleation of Tau aggregation can be neuroprotective.

PMID- 22611163
TI  - Molecular mechanisms of riboflavin responsiveness in patients with ETF-QO
      variations and multiple acyl-CoA dehydrogenation deficiency.
AB  - Riboflavin-responsive forms of multiple acyl-CoA dehydrogenation deficiency (RR
      MADD) have been known for years, but with presumed defects in the formation of
      the flavin adenine dinucleotide (FAD) co-factor rather than genetic defects of
      electron transfer flavoprotein (ETF) or electron transfer flavoprotein-ubiquinone
      oxidoreductase (ETF-QO). It was only recently established that a number of RR
      MADD patients carry genetic defects in ETF-QO and that the well-documented
      clinical efficacy of riboflavin treatment may be based on a chaperone effect that
      can compensate for inherited folding defects of ETF-QO. In the present study, we
      investigate the molecular mechanisms and the genotype-phenotype relationships for
      the riboflavin responsiveness in MADD, using a human HEK-293 cell expression
      system. We studied the influence of riboflavin and temperature on the steady
      state level and the activity of variant ETF-QO proteins identified in patients
      with RR-MADD, or non- and partially responsive MADD. Our results showed that
      variant ETF-QO proteins associated with non- and partially responsive MADD caused
      severe misfolding of ETF-QO variant proteins when cultured in media with
      supplemented concentrations of riboflavin. In contrast, variant ETF-QO proteins
      associated with RR-MADD caused milder folding defects when cultured at the same
      conditions. Decreased thermal stability of the variants showed that FAD does not
      completely correct the structural defects induced by the variation. This may
      cause leakage of electrons and increased reactive oxygen species, as reflected by
      increased amounts of cellular peroxide production in HEK-293 cells expressing the
      variant ETF-QO proteins. Finally, we found indications of prolonged association
      of variant ETF-QO protein with the Hsp60 chaperonin in the mitochondrial matrix,
      supporting indications of folding defects in the variant ETF-QO proteins.

PMID- 22611165
TI  - Epidermal growth factor regulates connexin 43 in the human epididymis: role of
      gap junctions in azoospermia.
AB  - BACKGROUND: Gap junctions (GJs) allow for direct communication between adjacent
      cells. They are composed of connexons consisting of transmembrane proteins,
      connexins (Cxs). The objectives of this study were to determine if GJ proteins
      GJA1 (Cx43), GJB1 (Cx32) and GJB2 (Cx26) are present in the epididymis of men
      with a normal epididymis, to assess whether or not Cx expression and localization
      are altered in azoospermic patients, and to determine if epidermal growth factor
      (EGF) regulates GJA1 expression. METHODS: Epididymides were obtained from men
      with localized testis cancer with active spermatogenesis and histologically
      normal epididymal tubule (group 1), men with non-obstructive azoospermia
      secondary to Sertoli-cell only syndrome (group 2) and from azoospermic men with
      normal spermatogenesis and epididymal obstruction (group 3). Epididymides were
      subdivided into three segments: caput, corpus and cauda. Quantitative real-time
      RT-PCR was performed to assess GJA1, GJB1, GJB2 and EGF receptor (EGFR) mRNA
      levels in epididymides from patients from each group (all n=3, except n=1 for
      caput blockage). A human caput epididymal cell line was then used to determine
      the role of EGFR signaling on the regulation of human epididymal GJA1. RESULTS:
      Real-time RT-PCR analysis revealed that GJA1, GJB1, GJB2 and EGFR were expressed
      along the human epididymis. In the cauda epididymidis of group 2 and 3 men, we
      observed a significant decrease in GJA1 (P=0.0456 and P=0.0465, respectively) and
      GJB1 (P=0.0450 and P=0.0497, respectively) mRNA levels when compared with group 1
      men. We also observed a decrease in EGFR mRNA levels (P=0.0358) in the cauda
      epididymidis of group 3 men when compared with group 1. Immunocytochemistry
      revealed that in the epididymis, GJA1 and EGFR were localized between basal and
      principal cells and between adjacent principal cells. In group 2 and 3 patients,
      however, we noted a dramatic increase in cytosolic immunostaining for both GJA1
      and EGFR in both principal and basal cells. Using a human caput epididymal cell
      line derived from fertile men, we demonstrated that changes in GJA1
      phosphorylation could be regulated by EGF (P=0.015) and the extracellular
      regulated kinase 1/2 signaling pathway (P=0.03). Furthermore, while the
      phosphoinositide-3-kinase (PI3K)/AKT signaling pathway did not alter GJA1
      phosphorylation, treatment with PI3K/AKT inhibitor LY294002 significantly
      (P=0.024) inhibited the EGF-stimulated increase in GJA1 total protein levels at
      24 h. Immunolocalization indicated that loss of PI3K/AKT signaling was associated
      with increased cytosolic localization of Cx43 in this cell line. CONCLUSIONS:
      Together, these data suggest that in azoospermic men decreased expression of EGFR
      may be responsible for decreasing GJA1 levels and increasing its cytosolic
      localization via the PI3K/AKT signaling pathway.

PMID- 22611166
TI  - The impact of IVF/ICSI on parental well-being and anxiety 1 year after
      childbirth.
AB  - BACKGROUND: More couples are delaying childbirth resulting in an increase of age
      related subfertility in women. Subfertility and assisted reproductive technology
      (ART) treatments may affect couples' psychological well-being. The aim of the
      present study was to investigate whether factors related to IVF/ICSI affect
      anxiety and mental health in couples 1 year after childbirth. METHOD: In this
      cohort study, we included couples with a singleton pregnancy following IVF/ICSI
      treatment (n=113) and subfertile couples who naturally conceived (NC; n=83).
      Parental trait anxiety (Dutch version of the Spielberger State-Trait Anxiety
      Inventory) and mental health (Dutch version of General Health Questionnaire) were
      assessed 1 year after childbirth. The influence of fertility-related factors was
      analyzed with logistic regression analyses. RESULTS: One hundred and ninety-six
      couples participated, 93% of those eligible. Trait anxiety and mental health were
      similar in IVF/ICSI and NC groups. However, NC fathers had more often mental
      health scores in the clinical range (21%) than fathers in the IVF/ICSI group
      (9%). The risk of having a trait anxiety or mental health score in the clinical
      range was reduced by the presence of one of the following factors: for females a
      higher number of IVF/ICSI treatment cycles, and a maternal cause of subfertility,
      for males having been treated by IVF/ICSI and a longer time to pregnancy.
      CONCLUSIONS: The present study indicates (i) that IVF/ICSI treatment is not
      associated with an increase in clinically relevant Spielberger State-Trait
      Anxiety Inventory and General Health Questionnaire scores in parents 1 year after
      childbirth and (ii) a higher number of IVF/ICSI treatment cycles and a longer
      time to pregnancy were associated with less trait anxiety and better mental
      health. A limitation of the study is the absence of mental health and trait
      anxiety data at baseline.

PMID- 22611164
TI  - Effect of tranexamic acid on surgical bleeding: systematic review and cumulative
      meta-analysis.
AB  - OBJECTIVE: To assess the effect of tranexamic acid on blood transfusion,
      thromboembolic events, and mortality in surgical patients. DESIGN: Systematic
      review and meta-analysis. DATA SOURCES: Cochrane central register of controlled
      trials, Medline, and Embase, from inception to September 2011, the World Health
      Organization International Clinical Trials Registry Platform, and the reference
      lists of relevant articles. STUDY SELECTION: Randomised controlled trials
      comparing tranexamic acid with no tranexamic acid or placebo in surgical
      patients. Outcome measures of interest were the number of patients receiving a
      blood transfusion; the number of patients with a thromboembolic event (myocardial
      infarction, stroke, deep vein thrombosis, and pulmonary embolism); and the number
      of deaths. Trials were included irrespective of language or publication status.
      RESULTS: 129 trials, totalling 10,488 patients, carried out between 1972 and 2011
      were included. Tranexamic acid reduced the probability of receiving a blood
      transfusion by a third (risk ratio 0.62, 95% confidence interval 0.58 to 0.65;
      P<0.001). This effect remained when the analysis was restricted to trials using
      adequate allocation concealment (0.68, 0.62 to 0.74; P<0.001). The effect of
      tranexamic acid on myocardial infarction (0.68, 0.43 to 1.09; P = 0.11), stroke
      (1.14, 0.65 to 2.00; P = 0.65), deep vein thrombosis (0.86, 0.53 to 1.39; P =
      0.54), and pulmonary embolism (0.61, 0.25 to 1.47; P=0.27) was uncertain. Fewer
      deaths occurred in the tranexamic acid group (0.61, 0.38 to 0.98; P = 0.04),
      although when the analysis was restricted to trials using adequate concealment
      there was considerable uncertainty (0.67, 0.33 to 1.34; P = 0.25). Cumulative
      meta-analysis showed that reliable evidence that tranexamic acid reduces the need
      for transfusion has been available for over 10 years. CONCLUSIONS: Strong
      evidence that tranexamic acid reduces blood transfusion in surgery has been
      available for many years. Further trials on the effect of tranexamic acid on
      blood transfusion are unlikely to add useful new information. However, the effect
      of tranexamic acid on thromboembolic events and mortality remains uncertain.
      Surgical patients should be made aware of this evidence so that they can make an
      informed choice.

PMID- 22611167
TI  - Potential impact on estimated treatment effects of information lost to follow-up
      in randomised controlled trials (LOST-IT): systematic review.
AB  - OBJECTIVE: To assess the reporting, extent, and handling of loss to follow-up and
      its potential impact on the estimates of the effect of treatment in randomised
      controlled trials. DESIGN: Systematic review. We calculated the percentage of
      trials for which the relative risk would no longer be significant under a number
      of assumptions about the outcomes of participants lost to follow-up. DATA
      SOURCES: Medline search of five top general medical journals, 2005-07.
      ELIGIBILITY CRITERIA: Randomised controlled trials that reported a significant
      binary primary patient important outcome. RESULTS: Of the 235 eligible reports
      identified, 31 (13%) did not report whether or not loss to follow-up occurred. In
      reports that did give the relevant information, the median percentage of
      participants lost to follow-up was 6% (interquartile range 2-14%). The method by
      which loss to follow-up was handled was unclear in 37 studies (19%); the most
      commonly used method was survival analysis (66, 35%). When we varied assumptions
      about loss to follow-up, results of 19% of trials were no longer significant if
      we assumed no participants lost to follow-up had the event of interest, 17% if we
      assumed that all participants lost to follow-up had the event, and 58% if we
      assumed a worst case scenario (all participants lost to follow-up in the
      treatment group and none of those in the control group had the event). Under more
      plausible assumptions, in which the incidence of events in those lost to follow
      up relative to those followed-up is higher in the intervention than control
      group, results of 0% to 33% trials were no longer significant. CONCLUSION:
      Plausible assumptions regarding outcomes of patients lost to follow-up could
      change the interpretation of results of randomised controlled trials published in
      top medical journals.

PMID- 22611168
TI  - Prophylaxis rates for venous thromboembolism and gastrointestinal bleeding in
      general medical patients: too low or too high?

PMID- 22611169
TI  - NICE recommends abiraterone for prostate cancer after manufacturer reduces price.

PMID- 22611173
TI  - Lung cancer incidence among Norwegian silicon carbide industry workers:
      associations with particulate exposure factors.
AB  - OBJECTIVES: An increased lung cancer risk associated with total dust exposure in
      the silicon carbide (SiC) industry has previously been reported. The aim of the
      present study was to examine the relative importance of specific exposure factors
      by using a comprehensive, historic job exposure matrix based on about 8000
      measurements. METHODS: Cumulative exposure to total and respirable dust,
      respirable quartz, cristobalite, and SiC particles and SiC fibres was assessed
      for 1687 long-term workers employed during 1913-2003 in the Norwegian SiC
      industry. Standardised incidence ratios for lung cancer, with follow-up during
      1953-2008, were calculated stratified by cumulative exposure categories. Poisson
      regression analyses were performed using both categorised and log-transformed
      cumulative exposure variables. RESULTS: The lung cancer incidence was about
      twofold increased at the highest level of exposure to each of the exposure
      factors (standardised incidence ratios 1.9-2.3 for all agents). Internal analyses
      showed associations between exposure level and lung cancer incidence for all
      investigated factors, but a significant trend only for total dust and
      cristobalite. In multivariate analyses, cristobalite showed the most consistent
      associations, followed by SiC fibres. CONCLUSIONS: The results indicated that
      crystalline silica in the form of cristobalite was the most important
      occupational exposure factor responsible for lung cancer excess in the Norwegian
      SiC industry. SiC fibres seemed to have an additional effect.

PMID- 22611174
TI  - Obstetric and perinatal outcomes in singleton pregnancies resulting from
      IVF/ICSI: a systematic review and meta-analysis.
AB  - BACKGROUND: Earlier reviews have suggested that IVF/ICSI pregnancies are
      associated with higher risks. However, there have been recent advances in the way
      IVF/ICSI is done, leading to some controversy as to whether IVF/ICSI singletons
      are associated with higher perinatal risks. The objective of this systematic
      review was to provide an up-to-date comparison of obstetric and perinatal
      outcomes of the singletons born after IVF/ICSI and compare them with those of
      spontaneous conceptions. METHODS: Extensive searches were done by two authors.
      The protocol was agreed a priori. PRISMA guidance was followed. The data were
      extracted in 2 * 2 tables. Risk ratio and risk difference were calculated on
      pooled data using Rev Man 5.1. Quality assessment of studies was performed using
      Critical Appraisal Skills programme. Sensitivity analysis was performed when the
      heterogeneity was high (I(2) > 50%). RESULTS: There were 20 matched cohort
      studies and 10 unmatched cohort studies included in this review. IVF/ICSI
      singleton pregnancies were associated with a higher risk (95% confidence
      interval) of ante-partum haemorrhage (2.49, 2.30-2.69), congenital anomalies
      (1.67, 1.33-2.09), hypertensive disorders of pregnancy (1.49, 1.39-1.59), preterm
      rupture of membranes (1.16, 1.07-1.26), Caesarean section (1.56, 1.51-1.60), low
      birthweight (1.65, 1.56-1.75), perinatal mortality (1.87, 1.48-2.37), preterm
      delivery (1.54, 1.47-1.62), gestational diabetes (1.48, 1.33-1.66), induction of
      labour (1.18, 1.10-1.28) and small for gestational age (1.39, 1.27-1.53).
      CONCLUSIONS: Singletons pregnancies after IVF/ICSI are associated with higher
      risks of obstetric and perinatal complications when compared with spontaneous
      conception. Further research is needed to determine which aspect of assisted
      reproduction technology poses most risk and how this risk can be minimized.

PMID- 22611175
TI  - Health and fertility in World Health Organization group 2 anovulatory women.
AB  - BACKGROUND: Disruption of ovulation occurs in different types of clinical
      infertility. The World Health Organization (WHO) has provided a classification of
      ovulation disorders. This review focuses on WHO group 2 anovulation. METHODS:
      Searches were performed in Medline/PubMed and EMBASE. Each subject summary was
      presented to the European Society of Human Reproduction and Embryology (ESHRE)
      Workshop Group, where omissions or disagreements were resolved by discussion.
      RESULTS: Disorders resulting in ovulatory disturbances are a relatively common
      cause of infertility. They occur most frequently in the context of WHO group 2
      anovulation as reflected, for example, in the polycystic ovary syndrome (PCOS).
      The aetiology of PCOS remains unclear but evidence exists for a multifactorial
      origin with a genetic predisposition. Women with PCOS show an increased time to
      pregnancy but their eventual family size is not necessarily reduced. Also their
      frequency of miscarriage does not appear increased. Clomiphene citrate is still
      the first-line treatment in subfertile anovulatory patients with PCOS, with
      gonadotrophins and laparoscopic ovarian surgery as second-line options. Aromatase
      inhibitors show promising results. CONCLUSIONS: Long-term health risks in
      patients with WHO group 2 anovulation demand their general health be monitored,
      even after their reproductive needs have been fulfilled. Metabolic and
      cardiovascular risk prevention in women with PCOS should start as early as
      possible. It is not easy to analyse the possible role of PCOS, independent of
      obesity, metabolic syndrome, insulin resistance and diabetes, on long-term
      health.

PMID- 22611176
TI  - Loss of XRN4 function can trigger cosuppression in a sequence-dependent manner.
AB  - OLE1 encodes an oleosin isoprotein, a major membrane protein of the lipid-reserve
      organelle in seeds known as the oil body. Transgenic Arabidopsis were generated
      to contain an artificial chimeric transgene composed of OLE1 and green
      fluorescent protein (GFP). Overexpression of the fusion protein allowed
      visualization of the oil body size and structure in living cells using
      fluorescence microscopy. Two mutants, xrn4-8(OleG) and xrn4-9(OleG), accumulating
      enlarged oil bodies with reduced GFP fluorescence were isolated from the
      mutagenized progeny of a transgenic plant. Both mutants contained a defect in
      EXORIBONUCLEASE4 (XRN4), a gene known to encode a ribonuclease that specifically
      degrades uncapped mRNAs. Transgene expression was silenced in these mutants, as
      demonstrated by the reduced levels of the transgene mRNA and its product, OLE1
      GFP. XRN4 loss of function also triggered cosuppression, i.e. simultaneous
      reduction in expression of the transgene and an endogenous OLE1 gene that shared
      a region of identical sequence. The enlarged oil bodies exhibiting reduced GFP
      fluorescence were formed in the xrn4-8(OleG) and xrn4-9(OleG) mutants due to the
      reduction of the endogenous OLE1 and the transgene product, OLE1-GFP,
      respectively. Cosuppression triggered by the xrn4 mutation also occurs for other
      genes such as PYK10, which encodes an endoplasmic reticulum (ER) body-resident
      beta-glucosidase. The overall results indicate that a loss of XRN4 function can
      potentially trigger the cosuppression in a sequence-dependent manner.

PMID- 22611177
TI  - Characterization of target site of aluminum phytotoxicity in photosynthetic
      electron transport by fluorescence techniques in tobacco leaves.
AB  - Aluminum (Al) toxicity limits crop yield in acidic soil through affecting diverse
      metabolic processes, especially photosynthesis. The aim of this work was to
      examine the effect of Al on photosynthetic electron transport in vivo as
      determined by chlorophyll fluorescence and delayed fluorescence of tobacco
      leaves. Results showed that Al treatment inhibited the photosynthetic rate and
      electron transfer, and decreased photosystem (PS) II photochemical activity in a
      time- and concentration-dependent manner, which could not be obviously alleviated
      by the addition of the reactive oxygen species (ROS) scavenger ascorbic acid
      (AsA). These results suggested that photosynthetic electron transfer chain
      components, especially PSII, might be directly damaged by Al instead of in an ROS
      dependent manner. Furthermore, the fluorescence imaging and biochemical analysis
      exhibited that Al, after entering the cells, could accumulate in the
      chloroplasts, which paralleled the decreased content of Fe in the chloroplast.
      The changes in the chlorophyll fluorescence decay curve, the delayed fluorescence
      decay curve and the chlorophyll fluorescence parameters indicated that Al,
      through interacting with or replacing the non-heme iron between Q(A) and Q(B),
      caused the inhibition of electron transfer between Q(A) and Q(B), resulting in
      PSII photochemical damage and inhibition of the photosynthetic rate. In summary,
      our results characterized the target site of Al phytotoxicity in photosynthetic
      electron transport, providing new insight into the mechanism of Al phytotoxicity
      induced chloroplast dysfunction and photosynthetic damage.

PMID- 22611179
TI  - Pharmacology and therapeutics of bronchodilators.
AB  - Bronchodilators are central in the treatment of of airways disorders. They are
      the mainstay of the current management of chronic obstructive pulmonary disease
      (COPD) and are critical in the symptomatic management of asthma, although
      controversies around the use of these drugs remain. Bronchodilators work through
      their direct relaxation effect on airway smooth muscle cells. at present, three
      major classes of bronchodilators, beta(2)-adrenoceptor (AR) agonists, muscarinic
      receptor antagonists, and xanthines are available and can be used individually or
      in combination. The use of the inhaled route is currently preferred to minimize
      systemic effects. Fast- and short-acting agents are best used for rescue of
      symptoms, whereas long-acting agents are best used for maintenance therapy. It
      has proven difficult to discover novel classes of bronchodilator drugs, although
      potential new targets are emerging. Consequently, the logical approach has been
      to improve the existing bronchodilators, although several novel broncholytic
      classes are under development. An important step in simplifying asthma and COPD
      management and improving adherence with prescribed therapy is to reduce the dose
      frequency to the minimum necessary to maintain disease control. Therefore, the
      incorporation of once-daily dose administration is an important strategy to
      improve adherence. Several once-daily beta(2)-AR agonists or ultra-long-acting
      beta(2)-AR-agonists (LABAs), such as indacaterol, olodaterol, and vilanterol, are
      already in the market or under development for the treatment of COPD and asthma,
      but current recommendations suggest the use of LABAs only in combination with an
      inhaled corticosteroid. In addition, some new potentially long-acting
      antimuscarinic agents, such as glycopyrronium bromide (NVA-237), aclidinium
      bromide, and umeclidinium bromide (GSK573719), are under development, as well as
      combinations of several classes of long-acting bronchodilator drugs, in an
      attempt to simplify treatment regimens as much as possible. This review will
      describe the pharmacology and therapeutics of old, new, and emerging classes of
      bronchodilator.

PMID- 22611180
TI  - The Sg-1 glycosyltransferase locus regulates structural diversity of triterpenoid
      saponins of soybean.
AB  - Triterpene saponins are a diverse group of biologically functional products in
      plants. Saponins usually are glycosylated, which gives rise to a wide diversity
      of structures and functions. In the group A saponins of soybean (Glycine max),
      differences in the terminal sugar species located on the C-22 sugar chain of an
      aglycone core, soyasapogenol A, were observed to be under genetic control.
      Further genetic analyses and mapping revealed that the structural diversity of
      glycosylation was determined by multiple alleles of a single locus, Sg-1, and led
      to identification of a UDP-sugar-dependent glycosyltransferase gene
      (Glyma07g38460). Although their sequences are highly similar and both glycosylate
      the nonacetylated saponin A0-alphag, the Sg-1(a) allele encodes the
      xylosyltransferase UGT73F4, whereas Sg-1(b) encodes the glucosyltransferase
      UGT73F2. Homology models and site-directed mutagenesis analyses showed that Ser
      138 in Sg-1(a) and Gly-138 in Sg-1(b) proteins are crucial residues for their
      respective sugar donor specificities. Transgenic complementation tests followed
      by recombinant enzyme assays in vitro demonstrated that sg-1(0) is a loss-of
      function allele of Sg-1. Considering that the terminal sugar species in the group
      A saponins are responsible for the strong bitterness and astringent aftertastes
      of soybean seeds, our findings herein provide useful tools to improve commercial
      properties of soybean products.

PMID- 22611181
TI  - Does the number of wires used to close a sternotomy have an impact on deep
      sternal wound infection?
AB  - OBJECTIVES: We studied the influence of the number of sternotomy mechanical
      fixation points on deep sternal wound infection (DSWI). METHODS: Between
      September 2007 and February 2011, 2672 patients underwent a standard peri-sternal
      wire closure following a median sternotomy for a first-time cardiac surgery. Data
      were collected during the study period. RESULTS: The mean age of the patients was
      66 +/- 11 and 1978 (74.0%) were male. The mean body mass index (BMI) was 28.9 +/-
      9.3 and the median of the logistic EuroSCORE was 3.14, with a range of 0.88-54.1.
      Postoperatively, 40 (1.5%) patients developed DSWI after 14 +/- 6 days, of whom
      39 (92.5%) had positive deep sternal wound specimen cultures, predominantly
      Staphylococci (62.5%). The risk of DSWI was significantly increased in patients
      in whom eight or fewer paired points of sternal wire fixation were used when
      compared with patients in whom nine or more paired points of fixation were used
      (P = 0.002). Preoperative myocardial infarction (P = 0.001), elevated BMI (P =
      0.046), bilateral internal mammary artery harvest (P < 0.0001), postoperative
      hypoxia (P < 0.0001), sepsis (P = 0.019) and postoperative inotrope use (P =
      0.007) significantly increased the risk of DSWI. CONCLUSIONS: DSWI is associated
      with hypoxia, ischaemia, sepsis and mechanical sternal instability. DSWI may be
      prevented by using nine or more paired fixation points when closing with standard
      peri-sternal wires.

PMID- 22611182
TI  - A randomized study comparing three groups of vein harvesting methods for coronary
      artery bypass grafting: endoscopic harvest versus standard bridging and open
      techniques.
AB  - OBJECTIVES: The use of an open vein harvesting (OVH) technique for saphenous vein
      harvesting (SVH) is associated with wound complications and delayed patient
      mobilization. This has led to the development of minimally invasive vein
      harvesting (MIVH) techniques, such as standard bridging and endoscopic SVH (EVH).
      This randomized trial was established to assess immediate clinical outcome and
      patient satisfaction in our centre. METHODS: A total of 150 consecutive patients
      were prospectively randomized into three groups. Group 1 consisted of 50 patients
      who underwent OVH, Group 2 consisted of 50 patients who underwent a standard
      bridging technique (SBT) and Group 3 consisted of 50 patients who underwent EVH.
      Each group was assessed for the incidence of wound infection, postoperative pain
      and satisfaction and the number of vein repairs using previously validated
      scoring systems. RESULTS: The MIVH techniques reduced the pain at hospital (P <
      0.001) and at 6 weeks (P < 0.001), and improved cosmesis (P < 0.001), compared
      with the OVH group. Patient satisfaction was greatest in the EVH group followed
      by the SBT and then the OVH group. The clinical markers of inflammation were
      reduced with an MIVHt. There were more vein repairs in the EVH compared with the
      OVH (P < 0.001) and the SBT (P = 0.04) groups. CONCLUSIONS: This study
      demonstrates that MIVH reduces wound morbidity. We believe that each technique
      has advantages and disadvantages, which should be considered during the selection
      of a harvesting procedure by both the patient and the surgeon.

PMID- 22611183
TI  - Intrathoracic gastric perforation: a late complication of an unknown postpartum
      recurrent hiatal hernia.
AB  - Diaphragmatic hernias occurring during pregnancy are an uncommon event. In very
      rare occasions, the clinical situation can suddenly worsen due to obstruction,
      torsion or infarction of the herniated viscera. Here, we describe a challenging
      case of a post-partum diaphragmatic hiatus hernia complicated by intrathoracic
      gastric perforation. A 23-year old woman was admitted at our hospital with a
      syndrome characterized by epigastralgy, dyspnoea and fever. She had previously
      undergone a laparoscopic antireflux surgery for hiatus hernia (6 years before)
      and a recent (4 months) unremarkable vaginal delivery. Due to the persistence of
      a pelvic pain after the delivery, she had been taking pain-killers as a self
      administered medication. A CT scan showed a massive left pleural effusion and a
      complete herniation of the stomach into the left hemithorax. After placing a
      chest drainage and removing up to 3000 ml of brownish purulent fluid, a repeat CT
      scan (with water soluble contrast swallow) showed a leak at the level of the
      stomach. At surgery, we observed a complete intrathoracic herniation through a
      large diaphragmatic hiatal defect and a small well-defined gastric ulcer. A
      primary repair of both the stomach and the diaphragm was performed. We take the
      opportunity presented by this report to briefly discuss the patho-physiological
      mechanisms underlying this unusual complication.

PMID- 22611184
TI  - Is fine-needle aspiration diagnosis of malignancy adequate prior to major lung
      resections including pneumonectomy?
AB  - A best evidence topic in thoracic surgery was written according to a structured
      protocol. The question addressed was whether a fine-needle aspiration (FNA)
      diagnosis is of sufficient reliability for the diagnosis of lung cancer prior to
      a major lung resection. Altogether, 112 papers were found using the reported
      search, of which 13 papers presented the best evidence to answer the clinical
      question. The author, journal, date and country of publication, patient group
      studied, study type, relevant outcomes, results and study weaknesses of these
      papers are tabulated. The tabulated studies include two meta-analyses, one
      systematic review, one randomized controlled trial (RCT) and nine cohort studies.
      The specificity reported for FNA in the diagnosis and staging of lung cancer
      ranged from 96.2 to 100%. One meta-analysis reported a specificity of 97%.
      Another meta-analysis reported a specificity of 98.8%. A systematic review
      reported a specificity of 97%. An RCT reported a specificity of 96.2-100%. We
      conclude that the FNA for lung cancer is reported to be highly specific prior to
      major lung resection with a very low false positive rate. However, although a
      false positive may occasionally be acceptable in lobectomies, where the lobes are
      often removed without histology, all steps should be taken to avoid a false
      positive result in pneumonectomy considering the serious consequences of
      embarking upon such an operation in the small number of patients with a false
      positive result, and we recommend that a positive FNA result should be confirmed
      by means of alternative sampling methods. We also acknowledge that obtaining an
      additional biopsy specimen would add to the risk of morbidity and costs;
      therefore, any benefits should be weighed against risks and additional costs.

PMID- 22611185
TI  - Percutaneous dilatation of right inferior pulmonary vein stenosis following
      single-lung transplant.
AB  - We present a 62-year old male who underwent right single-lung transplantation. An
      autologous pericardial rim was constructed at implantation, as there was
      insufficient donor atrial cuff. The patient was discharged home but deteriorated
      over 12 months resulting in oxygen dependency. Computed tomography scan showed
      stenosis of the right inferior pulmonary vein. The patient underwent pulmonary
      vein angioplasty under general anaesthesia in September 2007, which was
      successful and resulted in significant improvement in clinical status. However,
      his symptoms recurred 2 months later and a second attempt at angioplasty failed.
      He died 6 weeks later.

PMID- 22611186
TI  - Primary mucoepidermoid carcinoma of the trachea in a child.
AB  - Mucoepidermoid carcinoma of the trachea is a rare tumour, especially in the
      paediatric population. We report the case of a 9-year-old boy with mucoepidermoid
      carcinoma of the trachea that was preoperatively diagnosed as an intraluminal
      polypoid mass arising from the trachea and extending into the right main
      bronchus. A complete resection of the tumour with reconstruction and end-to-end
      anastomosis of the trachea was performed. The patient is now, 24 months after
      surgery, free of disease.

PMID- 22611187
TI  - Assessment of ground-based atmospheric observations for verification of
      greenhouse gas emissions from an urban region.
AB  - International agreements to limit greenhouse gas emissions require verification
      to ensure that they are effective and fair. Verification based on direct
      observation of atmospheric greenhouse gas concentrations will be necessary to
      demonstrate that estimated emission reductions have been actualized in the
      atmosphere. Here we assess the capability of ground-based observations and a high
      resolution (1.3 km) mesoscale atmospheric transport model to determine a change
      in greenhouse gas emissions over time from a metropolitan region. We test the
      method with observations from a network of CO(2) surface monitors in Salt Lake
      City. Many features of the CO(2) data were simulated with excellent fidelity,
      although data-model mismatches occurred on hourly timescales due to inadequate
      simulation of shallow circulations and the precise timing of boundary-layer
      stratification and destratification. Using two optimization procedures, monthly
      regional fluxes were constrained to sufficient precision to detect an increase or
      decrease in emissions of approximately 15% at the 95% confidence level. We argue
      that integrated column measurements of the urban dome of CO(2) from the ground
      and/or space are less sensitive than surface point measurements to the
      redistribution of emitted CO(2) by small-scale processes and thus may allow for
      more precise trend detection of emissions from urban regions.

PMID- 22611188
TI  - Demonstration of Al:ZnO as a plasmonic component for near-infrared metamaterials.
AB  - Noble metals such as gold and silver are conventionally used as the primary
      plasmonic building blocks of optical metamaterials. Making subwavelength-scale
      structural elements from these metals not only seriously limits the optical
      performance of a device due to high absorption, it also substantially complicates
      the manufacturing process of nearly all metamaterial devices in the optical
      wavelength range. As an alternative to noble metals, we propose to use heavily
      doped oxide semiconductors that offer both functional and fabrication advantages
      in the near-infrared wavelength range. In this letter, we replace a metal with
      aluminum-doped zinc oxide as a new plasmonic material and experimentally
      demonstrate negative refraction in an Al:ZnO/ZnO metamaterial in the near
      infrared range.

PMID- 22611178
TI  - G-protein-coupled receptors in adult neurogenesis.
AB  - The importance of adult neurogenesis has only recently been accepted, resulting
      in a completely new field of investigation within stem cell biology. The
      regulation and functional significance of adult neurogenesis is currently an area
      of highly active research. G-protein-coupled receptors (GPCRs) have emerged as
      potential modulators of adult neurogenesis. GPCRs represent a class of proteins
      with significant clinical importance, because approximately 30% of all modern
      therapeutic treatments target these receptors. GPCRs bind to a large class of
      neurotransmitters and neuromodulators such as norepinephrine, dopamine, and
      serotonin. Besides their typical role in cellular communication, GPCRs are
      expressed on adult neural stem cells and their progenitors that relay specific
      signals to regulate the neurogenic process. This review summarizes the field of
      adult neurogenesis and its methods and specifies the roles of various GPCRs and
      their signal transduction pathways that are involved in the regulation of adult
      neural stem cells and their progenitors. Current evidence supporting adult
      neurogenesis as a model for self-repair in neuropathologic conditions, adult
      neural stem cell therapeutic strategies, and potential avenues for GPCR-based
      therapeutics are also discussed.

PMID- 22611189
TI  - Allee effect promotes diversity in traveling waves of colonization.
AB  - Most mathematical studies on expanding populations have focused on the rate of
      range expansion of a population. However, the genetic consequences of population
      expansion remain an understudied body of theory. Describing an expanding
      population as a traveling wave solution derived from a classical reaction
      diffusion model, we analyze the spatio-temporal evolution of its genetic
      structure. We show that the presence of an Allee effect (i.e., a lower per capita
      growth rate at low densities) drastically modifies genetic diversity, both in the
      colonization front and behind it. With an Allee effect (i.e., pushed colonization
      waves), all of the genetic diversity of a population is conserved in the
      colonization front. In the absence of an Allee effect (i.e., pulled waves), only
      the furthest forward members of the initial population persist in the
      colonization front, indicating a strong erosion of the diversity in this
      population. These results counteract commonly held notions that the Allee effect
      generally has adverse consequences. Our study contributes new knowledge to the
      surfing phenomenon in continuous models without random genetic drift. It also
      provides insight into the dynamics of traveling wave solutions and leads to a new
      interpretation of the mathematical notions of pulled and pushed waves.

PMID- 22611190
TI  - Structure of the phage TP901-1 1.8 MDa baseplate suggests an alternative host
      adhesion mechanism.
AB  - Phages of the Caudovirales order possess a tail that recognizes the host and
      ensures genome delivery upon infection. The X-ray structure of the approximately
      1.8 MDa host adsorption device (baseplate) from the lactococcal phage TP901-1
      shows that the receptor-binding proteins are pointing in the direction of the
      host, suggesting that this organelle is in a conformation ready for host
      adhesion. This result is in marked contrast with the lactococcal phage p2
      situation, whose baseplate is known to undergo huge conformational changes in the
      presence of Ca(2+) to reach its active state. In vivo infection experiments
      confirmed these structural observations by demonstrating that Ca(2+) ions are
      required for host adhesion among p2-like phages (936-species) but have no
      influence on TP901-1-like phages (P335-species). These data suggest that these
      two families rely on diverse adhesion strategies which may lead to different
      signaling for genome release.

PMID- 22611191
TI  - Topographical and electrochemical nanoscale imaging of living cells using voltage
      switching mode scanning electrochemical microscopy.
AB  - We describe voltage-switching mode scanning electrochemical microscopy (VSM
      SECM), in which a single SECM tip electrode was used to acquire high-quality
      topographical and electrochemical images of living cells simultaneously. This was
      achieved by switching the applied voltage so as to change the faradaic current
      from a hindered diffusion feedback signal (for distance control and topographical
      imaging) to the electrochemical flux measurement of interest. This imaging method
      is robust, and a single nanoscale SECM electrode, which is simple to produce, is
      used for both topography and activity measurements. In order to minimize the
      delay at voltage switching, we used pyrolytic carbon nanoelectrodes with 6.5-100
      nm radii that rapidly reached a steady-state current, typically in less than 20
      ms for the largest electrodes and faster for smaller electrodes. In addition,
      these carbon nanoelectrodes are suitable for convoluted cell topography imaging
      because the RG value (ratio of overall probe diameter to active electrode
      diameter) is typically in the range of 1.5-3.0. We first evaluated the resolution
      of constant-current mode topography imaging using carbon nanoelectrodes. Next, we
      performed VSM-SECM measurements to visualize membrane proteins on A431 cells and
      to detect neurotransmitters from a PC12 cells. We also combined VSM-SECM with
      surface confocal microscopy to allow simultaneous fluorescence and topographical
      imaging. VSM-SECM opens up new opportunities in nanoscale chemical mapping at
      interfaces, and should find wide application in the physical and biological
      sciences.

PMID- 22611192
TI  - Aurora B kinase phosphorylates and instigates degradation of p53.
AB  - Aurora B is a mitotic checkpoint kinase that plays a pivotal role in the cell
      cycle, ensuring correct chromosome segregation and normal progression through
      mitosis. Aurora B is overexpressed in many types of human cancers, which has made
      it an attractive target for cancer therapies. Tumor suppressor p53 is a genome
      guardian and important negative regulator of the cell cycle. Whether Aurora B and
      p53 are coordinately regulated during the cell cycle is not known. We report that
      Aurora B directly interacts with p53 at different subcellular localizations and
      during different phases of the cell cycle (for instance, at the nucleus in
      interphase and the centromeres in prometaphase of mitosis). We show that Aurora B
      phosphorylates p53 at S183, T211, and S215 to accelerate the degradation of p53
      through the polyubiquitination-proteasome pathway, thus functionally suppressing
      the expression of p53 target genes involved in cell cycle inhibition and
      apoptosis (e.g., p21 and PUMA). Pharmacologic inhibition of Aurora B in cancer
      cells with WT p53 increased p53 protein level and expression of p53 target genes
      to inhibit tumor growth. Together, these results define a mechanism of p53
      inactivation during the cell cycle and imply that oncogenic hyperactivation or
      overexpression of Aurora B may compromise the tumor suppressor function of p53.
      We have elucidated the antineoplastic mechanism for Aurora B kinase inhibitors in
      cancer cells with WT p53.

PMID- 22611193
TI  - Connexin-43 prevents hematopoietic stem cell senescence through transfer of
      reactive oxygen species to bone marrow stromal cells.
AB  - Hematopoietic stem cell (HSC) aging has become a concern in chemotherapy of older
      patients. Humoral and paracrine signals from the bone marrow (BM) hematopoietic
      microenvironment (HM) control HSC activity during regenerative hematopoiesis.
      Connexin-43 (Cx43), a connexin constituent of gap junctions (GJs) is expressed in
      HSCs, down-regulated during differentiation, and postulated to be a self-renewal
      gene. Our studies, however, reveal that hematopoietic-specific Cx43 deficiency
      does not result in significant long-term competitive repopulation deficiency.
      Instead, hematopoietic Cx43 (H-Cx43) deficiency delays hematopoietic recovery
      after myeloablation with 5-fluorouracil (5-FU). 5-FU-treated H-Cx43-deficient HSC
      and progenitors (HSC/P) cells display decreased survival and fail to enter the
      cell cycle to proliferate. Cell cycle quiescence is associated with down
      regulation of cyclin D1, up-regulation of the cyclin-dependent kinase inhibitors,
      p21(cip1.) and p16(INK4a), and Forkhead transcriptional factor 1 (Foxo1), and
      activation of p38 mitogen-activated protein kinase (MAPK), indicating that H-Cx43
      deficient HSCs are prone to senescence. The mechanism of increased senescence in
      H-Cx43-deficient HSC/P cells depends on their inability to transfer reactive
      oxygen species (ROS) to the HM, leading to accumulation of ROS within HSCs. In
      vivo antioxidant administration prevents the defective hematopoietic
      regeneration, as well as exogenous expression of Cx43 in HSC/P cells.
      Furthermore, ROS transfer from HSC/P cells to BM stromal cells is also rescued by
      reexpression of Cx43 in HSC/P. Finally, the deficiency of Cx43 in the HM
      phenocopies the hematopoietic defect in vivo. These results indicate that Cx43
      exerts a protective role and regulates the HSC/P ROS content through ROS transfer
      to the HM, resulting in HSC protection during stress hematopoietic regeneration.

PMID- 22611194
TI  - Cleavage of Toll-like receptor 3 by cathepsins B and H is essential for
      signaling.
AB  - Toll-like receptor (TLR) 3 is an endosomal TLR that mediates immune responses
      against viral infections upon activation by its ligand double-stranded RNA, a
      replication intermediate of most viruses. TLR3 is expressed widely in the body
      and activates both the innate and adaptive immune systems. However, little is
      known about how TLR3 intracellular trafficking and maturation are regulated. Here
      we show that newly synthesized endogenous TLR3 is transported through the ER and
      Golgi apparatus to endosomes, where it is rapidly cleaved. TLR3 protein
      expression is up-regulated by its own ligand, leading to the accumulation of its
      cleaved form. In agreement with its proposed role as a transporter, UNC93B1
      expression is required for TLR3 cleavage and signaling. Furthermore, TLR3
      signaling and cleavage are sensitive to cathepsin inhibition. Cleavage occurs
      between aa 252 and 346, and results in a functional receptor that signals upon
      activation. A truncated form of TLR3 lacking the N-terminal 345 aa also signals
      from acidic compartments in response to ligand activation. Screening of the human
      cathepsin family by RNA interference identified cathepsins B and H as key
      mediators of TLR3 processing. Taken together, our data indicate that TLR3
      proteolytic processing is essential for its function, and suggest a mechanism of
      tight control of TLR3 signaling and thus immunity.

PMID- 22611196
TI  - Sphingobacterium hotanense sp. nov., isolated from soil of a Populus euphratica
      forest, and emended descriptions of Sphingobacterium daejeonense and
      Sphingobacterium shayense.
AB  - A novel Gram-staining-negative bacterial strain, designated XH4(T), was isolated
      from soil of a Populus euphratica forest in the Hotan River valley, Xinjiang
      Uyghur autonomous region, PR China. The cells were strictly aerobic, non-motile,
      short rods. The isolate grew optimally at 37  degrees C and at pH 7.0-8.0. Based
      on 16S rRNA gene sequence analysis, strain XH4(T) belonged to the genus
      Sphingobacterium and was closely related to Sphingobacterium mizutaii ATCC
      33299(T) (96.1 % sequence similarity). The DNA G+C content was 41.2 mol%. The
      major polar lipid of strain XH4(T) was phosphatidylethanolamine, and several
      unidentified polar lipids were also present. Strain XH4(T) showed the typical
      chemotaxonomic features of the genus Sphingobacterium, with the presence of
      ceramide phosphorylethanolamine 2 (CerPE-2) as the major ceramide. The major
      cellular fatty acids of strain XH4(T) were iso-C15 : 0 (34.0 %), summed feature 3
      (C16 : 1omega7c and/or C16 : 1omega6c; 20.7 %) and iso-C17 : 0 3-OH (14.7 %). The
      predominant isoprenoid quinone was MK-7. On the basis of phenotypic data and
      phylogenetic inference, strain XH4(T) represents a novel species of the genus
      Sphingobacterium, for which the name Sphingobacterium hotanense sp. nov. is
      proposed. The type strain is XH4(T) ( = NRRL B-59204(T)  = CCTCC AB 209007(T)).
      Emended descriptions of Sphingobacterium daejeonense and Sphingobacterium
      shayense are also given.

PMID- 22611195
TI  - Distinct perturbation of the translatome by the antidiabetic drug metformin.
AB  - Metformin has been reported to lower cancer incidence among type II diabetics.
      Metformin exhibits antiproliferative and antineoplastic effects associated with
      inhibition of mammalian target of rapamycin complex 1 (mTORC1), but the
      mechanisms are poorly understood. We provide a unique genome-wide analysis of
      translational targets of canonical mTOR inhibitors (rapamycin and PP242) compared
      with metformin, revealing that metformin controls gene expression at the level of
      mRNA translation to an extent comparable to that of canonical mTOR inhibitors.
      Importantly, metformin's antiproliferative activity can be explained by selective
      translational suppression of mRNAs encoding cell-cycle regulators via the
      mTORC1/eukaryotic translation initiation factor 4E-binding protein pathway. Thus,
      metformin selectively inhibits translation of mRNAs encoding proteins that
      promote neoplastic proliferation, which should facilitate studies on metformin
      and related biguanides in cancer prevention and treatment.

PMID- 22611197
TI  - Phyllobacterium endophyticum sp. nov., isolated from nodules of Phaseolus
      vulgaris.
AB  - A strain, PEPV15(T), was isolated from a nodule on Phaseolus vulgaris grown in
      soil in northern Spain. Phylogenetic analyses of 16S rRNA and atpD genes showed
      that this strain belongs to the genus Phyllobacterium. The most closely related
      species were, in both cases, Phyllobacterium brassicacearum, Phyllobacterium
      bourgognense and Phyllobacterium trifolii, the type strains of which gave
      sequence similarities of 98.9, 98.6 and 98.4 %, respectively, in the 16S rRNA
      gene and 88.1, 87.5 and 88.7 %, respectively, in the atpD gene. PEPV15(T)
      contained Q-10 as the major quinone (88 %) and low amounts of Q-9 (12 %). It
      differed from its closest relatives in its growth in diverse culture conditions
      and in the assimilation of several carbon sources. The strain was not able to
      produce nodules in Phaseolus vulgaris. The results of DNA-DNA hybridization,
      phenotypic tests and fatty acid analyses confirmed that this strain represents a
      novel species of the genus Phyllobacterium for which the name Phyllobacterium
      endophyticum sp. nov. is proposed; the type strain is PEPV15(T) ( = LMG 26470(T)
      = CECT 7949(T)). An emended description of the genus Phyllobacterium is also
      provided.

PMID- 22611198
TI  - Flavobacterium tilapiae sp. nov., isolated from a freshwater pond, and emended
      descriptions of Flavobacterium defluvii and Flavobacterium johnsoniae.
AB  - A bacterial strain, designated Ruye-71(T), was isolated from a freshwater
      tilapiine cichlid fish culture pond in Taiwan and characterized in a taxonomic
      study using a polyphasic approach. Cells of strain Ruye-71(T) were Gram-stain
      negative, strictly aerobic, yellow-pigmented rods that were motile by gliding.
      Growth occurred at 10-30  degrees C (optimum, 15-30  degrees C), at pH 7.0-8.0
      (optimum, pH 8.0) and with 0-2 % NaCl (optimum, 0-1 %). Phylogenetic analyses
      based on 16S rRNA gene sequences showed that strain Ruye-71(T) belonged to the
      genus Flavobacterium and was most closely related to Flavobacterium defluvii
      EMB117(T), with a 16S rRNA gene sequence similarity of 97.7 %. Strain Ruye-71(T)
      contained iso-C15 : 0, summed feature 3 (comprising C16 : 1omega6c and/or C16 :
      1omega7c), C16 : 0, C16 : 0 3-OH, iso-C15 : 0 3-OH and iso-C17 : 0 3-OH as major
      fatty acids. The major isoprenoid quinone was MK-6. The polar lipid profile
      consisted of phosphatidylethanolamine and several unidentified polar lipids. The
      DNA G+C content of the genomic DNA of strain Ruye-71(T) was 39.2 mol%. The mean
      level of DNA-DNA relatedness between strain Ruye-71(T) and Flavobacterium
      defluvii DSM 17963(T) was 39.9+/-1.2 %. On the basis of phylogenetic inference
      and phenotypic data, strain Ruye-71(T) should be classified as representing a
      novel species, for which the name Flavobacterium tilapiae sp. nov. is proposed.
      The type strain is Ruye-71(T) ( = BCRC 80262(T) = KCTC 23312(T)). Emended
      descriptions of Flavobacterium defluvii and Flavobacterium johnsoniae are also
      proposed.

PMID- 22611199
TI  - Pelagimonas varians gen. nov., sp. nov., isolated from the southern North Sea.
AB  - A heterotrophic, Gram-stain-negative, aerobic bacterium, designated strain SH4
      1(T), was obtained from a seawater sample collected from the southern North Sea
      during a phytoplankton bloom. The 16S rRNA gene sequence comparison revealed
      affiliation to the Roseobacter clade (class Alphaproteobacteria) with
      Sulfitobacter marinus SW-265(T) as the most closely related characterized strain,
      showing 97.2 % 16S rRNA gene sequence similarity. Calculation of phylogenetic
      trees based on 16S rRNA gene sequences indicated, however, that members of the
      genus Roseobacter, Roseobacter denitrificans Och 114(T) and Roseobacter litoralis
      Och 149(T) (95 % and 96 % sequence similarity, respectively) fall between strain
      SH4-1(T) and the Sulfitobacter cluster including Oceanibulbus indolifex HEL-45(T)
      (>=95.4 % sequence similarity). Cells of strain SH4-1(T) are irregular rods with
      at least one flagellum. Optimal growth occurred between 28 and 32  degrees C and
      at a pH between 7.0 and 8.5. Cells require the vitamin nicotinic acid amide as
      well as sodium ions for growth. The DNA G+C content was 55.1 mol%. The fatty
      acids (>1 %) comprised C10 : 0 3-OH, C12 : 1, C14 : 1 3-OH, C16 : 0, C18 : 0, C18
      : 2, C18 : 1omega7c and 11-methyl C18 : 1omega7c. The polar lipid pattern
      indicated the presence of phosphatidylcholine, phosphatidylglycerol,
      phosphatidylethanolamine, diphosphatidylglycerol,
      phosphatidylmonomethylethanolamine, an unidentified aminolipid, one unidentified
      phospholipid and one other unidentified lipid. On the basis of phenotypic,
      chemotaxonomic and phylogenetic differences, strain SH4-1(T) represents a novel
      species in a new genus within the family Rhodobacteraceae, for which we propose
      the name Pelagimonas varians gen. nov., sp. nov. The type strain of the type
      species is SH4-1(T) ( = DSM 23678(T) = LMG 26343(T) = CIP 110297(T)).

PMID- 22611200
TI  - Ornithinibacillus halophilus sp. nov., a moderately halophilic, Gram-stain
      positive, endospore-forming bacterium from a hypersaline lake.
AB  - A novel Gram-stain-positive, moderately halophilic bacterium, designated strain
      G8B(T), was isolated from water of the hypersaline lake Aran-Bidgol in Iran and
      characterized taxonomically using a polyphasic approach. Cells of strain G8B(T)
      were rod-shaped, motile and produced oval endospores at a terminal position in
      swollen sporangia. Strain G8B(T) was strictly aerobic, catalase-positive and
      oxidase-negative. The strain was able to grow at NaCl concentrations of 0.5-12.5
      % (w/v), with optimum growth occurring at 5-7.5 % (w/v) NaCl. The optimum
      temperature and pH for growth were 35-40  degrees C and pH 7.5-8.0, respectively.
      On the basis of 16S rRNA gene sequence analysis, strain G8B(T) was shown to
      belong to the genus Ornithinibacillus within the phylum Firmicutes and showed
      closest phylogenetic similarity with Ornithinibacillus bavariensis WSBC 24001(T)
      (97.6 %). The DNA G+C content of strain G8B(T) was 36.9 mol%. The major cellular
      fatty acids of strain G8B(T) were anteiso-C15 : 0, anteiso-C17 : 0, iso-C15 : 0
      and iso-C16 : 0, and its polar lipid pattern consisted of phosphatidylglycerol,
      diphosphatidylglycerol, four unknown phospholipids and an unknown aminolipid. The
      isoprenoid quinones were MK-7 (98 %) and MK-8 (2 %). Strain G8B(T) contained a
      peptidoglycan of type A4beta, l-Orn-d-Asp. All these features confirmed the
      placement of isolate G8B(T) within the genus Ornithinibacillus. DNA-DNA
      hybridization experiments revealed a low level of relatedness (6 %) between
      strain G8B(T) and Ornithinibacillus bavariensis DSM 15681(T). On the basis of
      evidence from this study, a novel species of the genus Ornithinibacillus,
      Ornithinibacillus halophilus sp. nov., is proposed, with strain G8B(T) ( = IBRC-M
      10683(T) = KCTC 13822(T)) as the type strain.

PMID- 22611201
TI  - Pseudorhodobacter antarcticus sp. nov., isolated from Antarctic intertidal sandy
      sediment, and emended description of the genus Pseudorhodobacter Uchino et al.
      2002 emend. Jung et al. 2012.
AB  - A Gram-negative, aerobic, non-motile, pink-pigmented and rod-shaped strain,
      designated ZS3-33(T), was isolated from Antarctic intertidal sandy sediment. The
      strain grew optimally at 15  degrees C and with 1.0 % (w/v) NaCl. It reduced
      nitrate to nitrite and hydrolysed Tween 20. It could not produce
      bacteriochlorophyll a. The predominant cellular fatty acid was C18 : 1omega7c and
      the predominant respiratory quinone was Q-10. The major polar lipids were
      phosphatidylglycerol, phosphatidylcholine, two unidentified aminophospholipids
      and an unidentified aminolipid. Analyses of 16S rRNA gene sequences revealed that
      strain ZS3-33(T) belonged to the genus Pseudorhodobacter, showing 97.4 %
      similarity to the type strain of Pseudorhodobacter ferrugineus and 95.3 %
      similarity to the type strain of Pseudorhodobacter aquimaris. Levels of gyrB gene
      sequence similarity between strain ZS3-33(T) and the type strains of P.
      ferrugineus and P. aquimaris were 87.6 and 81.7 %, respectively. DNA-DNA
      relatedness between strain ZS3-33(T) and P. ferrugineus DSM 5888(T) was 56.6 %.
      The genomic DNA G+C content of strain ZS3-33(T) was 57.1 mol%. Based on data from
      this polyphasic study, strain ZS3-33(T) represents a novel species of the genus
      Pseudorhodobacter, for which the name Pseudorhodobacter antarcticus sp. nov. is
      proposed. The type strain is ZS3-33(T) ( = CGMCC 1.10836(T) = KCTC 23700(T)). An
      emended description of the genus Pseudorhodobacter Uchino et al. 2002 emend. Jung
      et al. 2012 is also proposed.

PMID- 22611202
TI  - Bacillus ginsengisoli sp. nov., isolated from soil of a ginseng field.
AB  - A novel bacterial strain DCY53(T) was isolated from a soil sample from a ginseng
      field and was characterized using a polyphasic approach. Cells were Gram-reaction
      positive, rod-shaped, endospore-forming and motile with flagella. The strain was
      aerobic, catalase- and oxidase-positive, optimum growth temperature and pH were
      30-37  degrees C and 6.0-7.5, respectively. On the basis of 16S rRNA gene
      sequence analysis, strain DCY53(T) was shown to belong to the genus Bacillus and
      the closest phylogenetic relatives were Bacillus pocheonensis KCTC 13943(T) (98.3
      %), Bacillus bataviensis LMG 21833(T) (98.0 %), Bacillus soli LMG 21838(T) (97.9
      %), Bacillus drentensis LMG 21831(T) (97.8 %), Bacillus niacini DSM 2923(T) (97.8
      %), Bacillus novalis LMG 21837(T) (97.7 %), Bacillus vireti LMG 21834(T) (97.6 %)
      and Bacillus fumarioli LMG 17489(T) (97.3 %). The DNA G+C content was 43.6 mol%
      and the predominant respiratory quinone was MK-7. The major fatty acids were iso
      C14 : 0, iso-C15 : 0, iso-C16 : 0 and anteiso-C15 : 0. The DNA-DNA relatedness
      with closest relatives was below 55 %. The results of the genotypic analysis in
      combination with chemotaxonomic and physiological data demonstrated that DCY53(T)
      represented a novel species within the genus Bacillus, for which we propose the
      name Bacillus ginsengisoli. The type strain is DCY53(T) ( = KCTC 13945(T) = JCM
      17335(T)).

PMID- 22611203
TI  - Halobaculum magnesiiphilum sp. nov., a magnesium-dependent haloarchaeon isolated
      from commercial salt.
AB  - Two extremely halophilic archaea, strains MGY-184(T) and MGY-205, were isolated
      from sea salt produced in Japan and rock salt imported from Bolivia,
      respectively. Both strains were pleomorphic, non-motile, Gram-negative and
      required more than 5 % (w/v) NaCl for growth, with optimum at 9-12 %, in the
      presence of 2 % (w/v) MgCl2 . 6H2O. In the presence of 18 % (w/v) MgCl2 . 6H2O,
      however, both strains showed growth even at 1.0 % (w/v) NaCl. Both strains
      possessed two 16S rRNA genes (rrnA and rrnB), and they revealed closest
      similarity to Halobaculum gomorrense JCM 9908(T), the single species with a
      validly published name of the genus Halobaculum, with similarity of 97.8 %. The
      rrnA and rrnB genes of both strains were 100 % similar. The rrnA genes were 97.6
      % similar to the rrnB genes in both strains. DNA G+C contents of strains MGY
      184(T) and MGY-205 were 67.0 and 67.4 mol%, respectively. Polar lipid analysis
      revealed that the two strains contained phosphatidylglycerol and
      phosphatidylglycerol phosphate methyl ester derived from C20C20 archaeol. The DNA
      DNA hybridization value between the two strains was 70 % and both strains showed
      low levels of DNA-DNA relatedness (48-50 %) with Halobaculum gomorrense JCM
      9908(T). Physiological and biochemical characteristics allowed differentiation of
      strains MGY-184(T) and MGY-205 from Halobaculum gomorrense JCM 9908(T).
      Therefore, strains MGY-184(T) and MGY-205 represent a novel species of the genus
      Halobaculum, for which the name Halobaculum magnesiiphilum sp. nov. is proposed;
      the type strain is MGY-184(T) ( = JCM 17821(T) = KCTC 4100(T)).

PMID- 22611204
TI  - Radiation exposure in interventional procedures.
AB  - The aim of this study was to estimate radiation doses patients and staff are
      exposed to during interventional procedures (IPs), compare them with the
      international diagnostic reference levels and to develop initial National
      Diagnostic Reference Levels. The IP survey was undertaken as the initial task of
      which, retrospective data were collected from the only four Kenyan hospitals
      carrying out interventional radiology and cardiology procedures at the time of
      the study. Real-time measurement of radiation dose to patients and staff during
      these procedures was done. To the patients, kerma-area product (KAP) and
      fluoroscopy time measurements were done using an in-built KAP meter, while peak
      skin dose (PSD) was measured using slow Extended Dose Range (EDR2((r)))
      radiographic films. The staff occupational doses were measured using individual
      thermoluminescence dosemeters. The maximum and minimum KAP values were found to
      be 137.1 and 4.2 Gy cm(2), while the measured PSD values were 740 and 52 mGy,
      respectively. The fluoroscopic time range was between 3.3 and 70 min. The staff
      doses per procedure ranged between 0.05 and 1.41 mSv for medical doctors, 0.03
      and 1.16 mSv for nurses, 0.04 and 0.78 mSv for radiographers and 0.04 and 0.88
      mSv for clinical staff. The measured patient PSDs were within the threshold limit
      for skin injuries. However, with the current few IP specialists, an annual
      increase in workload as determined in the study will result in the International
      Commission on Radiation Protection annual eye lens dose limit being exceeded by
      10 %. A concerted effort is required to contain these dose levels through use of
      protective gear, optimisation of practice and justification.

PMID- 22611205
TI  - Gamma radiation measurements and Monte Carlo computations following myocardial
      perfusion imaging with 201Tl.
AB  - In the current study, the time-dependent retention of (201)Tl-thallous chloride
      (111 MBq) was measured in a 56-y-old man undergoing myocardial perfusion imaging.
      For 23 d following the (201)Tl injection, total-body retained activity was
      measured by (i) in situ gamma spectrometry using a portable high-purity germanium
      (HPGe) detector and (ii) ex vivo urine radioassay using a shielded HPGe detector.
      The time-dependent decrease in total-body activity followed a monoexponential
      function, exp(-0.011 t), with an excellent correlation (R(2)=0.9988) between the
      experimental data and the fitted values. The effective half-life, Teff, of
      (201)Tl (physical half-life, Tph: 72.9 h) was therefore 63 h and the biological
      half-life, Tb, 463 h=19.3 d, identical to those measured in the same patient in
      1997 (i.e. 14 y ago). The time-dependent decrease in the urine activity
      concentration, which followed a monoexponential function, exp(-0.0115 t),
      corroborated the foregoing results. The correlation (R(2)=0.9939) between the
      experimental data and the fitted values was again excellent. The effective half
      life, Teff, was 60.26 h and the biological half-life, Tb, 348 h=14.5 d. Monte
      Carlo simulation using a simple model of the patient as a unit-density cylinder
      filled with water and containing a uniform distribution of (201)Tl yielded photon
      flux results in reasonable agreement with the measured data.

PMID- 22611206
TI  - Personal dose analysis of TLD glow curve data from individual monitoring records.
AB  - Radiation exposure of workers in Ghana have been estimated on the basis of
      personal dose records of the occupationally exposed in medical, industrial and
      research/teaching practices for the period 2008-09. The estimated effective doses
      for 2008 are 0.400, 0.495 and 0.426 mSv for medical, industrial and
      research/teaching practices, respectively. The corresponding collective effective
      doses are 0.128, 0.044 and 0.017 person-Sv, respectively. Similarly, the
      effective doses recorded in 2009 are 0.448, 0.545 and 0.388 mSv, respectively
      with corresponding collective effective doses of 0.108, 0.032 and 0.012 person
      Sv, respectively. The study shows that occupational exposure in Ghana is skewed
      to the lower doses (between 0.001 and 0.500 mSv). A statistical analysis of the
      effective doses showed no significant difference at p < 0.05 among the means of
      the effective doses recorded in various practices.

PMID- 22611207
TI  - Thermoluminescence and photoluminescence in the NaCaPO4:Dy3+ phosphor.
AB  - Dy(3+)-doped NaCaPO(4) phosphor was synthesised at an initiating combustion
      temperature of 600 degrees C, using urea as the fuel. The crystallinity of the
      phosphor was investigated by using X-ray diffraction. The photoluminescence and
      thermoluminescence (TL) behaviours of NaCaPO(4):Dy(3+) phosphor was also studied.
      It has a simple TL glow curve structure, which does not change when exposed to
      gamma-rays. A TL glow peak is observed at 230 degrees C and TL intensity is
      around 1.15 times more compared with commercial CaSO(4):Dy TLD phosphor. The TL
      characteristics of the phosphor prepared show that it has good sensitivity,
      linear response with gamma-rays exposure, emission in the blue-yellow regions of
      the spectrum, negligible fading and excellent reusability. These results make
      Dy(3+)-doped NaCaPO(4) phosphor attractive for TLD applications.

PMID- 22611208
TI  - Clinical signs of cardiovascular effects secondary to suspected pimobendan
      toxicosis in five dogs.
AB  - The purpose of this study was to review the medical records of dogs that were
      either suspected or known to have ingested large doses of pimobendan and to
      describe the clinical signs associated with pimobendan toxicosis. The database of
      Pet Poison Helpline, an animal poison control center located in Minneapolis, MN,
      was searched for cases involving pimobendan toxicosis from Nov 2004 to Apr 2010.
      In total, 98 cases were identified. Of those, seven dogs that ingested between
      2.6 mg/kg and 21.3 mg/kg were selected for further evaluation. Clinical signs
      consisted of cardiovascular abnormalities, including severe tachycardia (4/7),
      hypotension (2/7), and hypertension (2/7). In two dogs, no clinical signs were
      seen. Despite a wide safety profile, large overdoses of pimobendan may present
      risks for individual pets. Prompt decontamination, including emesis induction and
      the administration of activated charcoal, is advised in the asymptomatic patient.
      Symptomatic and supportive care should include the use of IV fluid therapy to
      treat hypotension and address hydration requirements and blood pressure and
      electrocardiogram monitoring with high-dose toxicosis. Practitioners should be
      aware of the clinical signs associated with high-dose pimobendan toxicosis. Of
      the dogs reported herein, all were hospitalized, responded to supportive care,
      and survived to discharge within 24 hr of exposure.

PMID- 22611209
TI  - The use of IV lipid emulsion for lipophilic drug toxicities.
AB  - IV lipid emulsion (ILE) therapy is emerging as a potential antidote for
      lipophilic drug toxicities in both human and veterinary medicine. ILE has already
      gained acceptance in human medicine as a treatment of local anesthetic systemic
      toxicity, but its mechanism of action, safety margins, and standardized dosing
      information remains undetermined at this time. Experimental and anecdotal use of
      ILE in the human and veterinary literature, theorized mechanisms of action,
      current dosing recommendations, potential adverse effects, and indications for
      use in human and veterinary emergency medicine are reviewed herein.

PMID- 22611210
TI  - Bilateral ventriculocordectomy via ventral laryngotomy for idiopathic laryngeal
      paralysis in 88 dogs.
AB  - Bilateral ventriculocordectomy through a ventral median laryngotomy was performed
      for the treatment of idiopathic laryngeal paralysis in 88 dogs. The purpose of
      this retrospective analysis was to provide long-term follow-up for a large number
      of dogs surgically managed with this technique. A combination of medical record
      and completed client questionnaire information provided short-term (14 days)
      follow-up for 88 dogs and long-term (>6 mo) follow-up for 42 dogs. Major short
      term postoperative complications were identified in 3 of 88 (3.4%) patients.
      Major long-term complications were identified in 3 of 42 (7.1%) patients. The
      results of surgery were considered to be very satisfactory in 93% and
      unsatisfactory in 7%. Three dogs in this series developed aspiration pneumonia.
      Bilateral ventriculocordectomy through a ventral median laryngotomy is associated
      with a low incidence of both short- and long-term complications. Due to the ease
      of this procedure, the minimal surgical trauma to the patient, and the
      satisfactory results, this surgery should be considered an option for the
      treatment of idiopathic laryngeal paralysis in the dog.

PMID- 22611211
TI  - Novel cutaneous use of implantable loop recorders in two dogs with unexplained
      episodes of collapse.
AB  - Determining the cause of episodes of collapse can be difficult. Even in patients
      with frequent collapsing episodes due to cardiac causes, diagnostic surface
      electrocardiogram and 24 hr ambulatory electrocardiographic (Holter) monitoring
      are sometimes inconclusive. Event monitors with multiple leads can be challenging
      to use in veterinary medicine over long periods of time due to lead dislodgment.
      Implantable leadless loop recorders (ILRs) are useful, but owners are sometimes
      unwilling to have an ILR implanted due to the associated risks and/or costs. In
      this case report, the authors describe the use of cutaneously placed ILRs in two
      dogs with unexplained episodes of collapse/exercise intolerance. Data recorded
      provided clinically useful information. Cutaneously placed ILRs can be used
      effectively in veterinary medicine to evaluate patients with unexplained episodes
      of collapse.

PMID- 22611212
TI  - Pharmaceutical evaluation of compounded trilostane products.
AB  - Compounded trilostane capsules (15 mg, 45 mg, or 100 mg) were purchased from
      eight pharmacies and assayed for content and dissolution characteristics.
      Capsules made in-house containing either inert material or 15 mg of the licensed
      product and proprietary capsules (30 mg and 60 mg) served as controls. Findings
      were compared with regulatory specifications for the licensed product.
      Altogether, 96 batches of compounded trilostane and 16 control batches underwent
      analysis. In total, 36 of 96 (38%) compounded batches were below the acceptance
      criteria for content. The average percentage label claim (% LC) for each batch
      ranged from 39% to 152.6% (mean, 97.0%). The range of average % LC for the
      controls was 96.1-99.6% (mean, 97.7%). The variance in content of the purchased
      compounded products was substantially greater than for the controls (234.65
      versus 1.27; P<0.0001). All control batches exceeded the acceptance criteria for
      dissolution, but 19 of 96 batches (20%) of purchased compounded products did not.
      Mean percent dissolution for the purchased compounded products was lower than for
      controls (75.96% versus 85.12%; P=0.013). These findings indicate that trilostane
      content of compounded capsules may vary from the prescribed strength, and
      dissolution characteristics may not match those of the licensed product. The use
      of compounded trilostane products may therefore negatively impact the management
      of dogs with hyperadrenocorticism.

PMID- 22611213
TI  - Diagnosis and treatment of tracheal basal cell carcinoma in a Maine coon and long
      term outcome.
AB  - A 6 yr old castrated male Maine coon presented with a 2 wk history of progressive
      dyspnea. Thoracic radiographs revealed a 2 cm diameter intratracheal mass at the
      level of the fourth rib. The tracheal mass was marginally excised via a
      combination of resection and anastomosis. Infiltrative basal cell carcinoma (BCC)
      with nodular osseous metaplasia was diagnosed. The thoracic trachea was then
      irradiated postoperatively for definitive treatment. The cat remained
      asymptomatic following surgical excision and radiation therapy for 32 mo when
      this report was written. The purpose of this report is to describe the treatment
      and long-term outcome of a Maine coon diagnosed with, and treated for, tracheal
      BCC.

PMID- 22611214
TI  - Anatomic distribution and clinical findings of intermuscular lipomas in 17 dogs
      (2005-2010).
AB  - Intermuscular lipomas (IML) in dogs can be associated with ominous clinical
      signs, especially in the thoracic limb. However, the prognosis is excellent
      following surgical excision. There is a paucity of information in the veterinary
      literature regarding IML. Our objective was to describe the anatomical location,
      imaging techniques, and clinical findings in a series of dogs that were diagnosed
      and treated for IML. The prevalence of thoracic versus pelvic limb IML was not
      different. Most IML of the thoracic limb were located in the axilla. Operative
      time for IML of the thoracic and pelvic limb averaged 60 minutes. Complications
      were rare after marginal surgical excision and recurrence was not seen in any of
      the cases in this report. Intermuscular lipomas of the axilla are as common as
      IML of the caudal thigh. Surgical treatment of both axillary and caudal-thigh IML
      is associated with an excellent prognosis in dogs.

PMID- 22611215
TI  - Goiter with vascular anomalies in a litter of Polish Lowland sheepdogs.
AB  - At approximately 4-5 mo of age, three Polish Lowland sheepdog puppies from a
      single litter of eight puppies presented to their respective primary
      veterinarians with bilateral subcutaneous masses in their ventral cervical
      regions. Evaluation, including thyroid function testing, surgical exploration
      with resection, computed tomography, and angiography, identified the masses as
      enlarged thyroid glands with severely dilated and abnormal vasculature in the
      regions of the glands. The dogs were also found to have serum concentrations of
      thyroid hormones that were below the reference ranges. None of the three dogs
      showed clinical signs of hypothyroidism, except for the presence of goiter. One
      dog also had a patent ductus arteriosus that was surgically repaired. All dogs
      were clinically normal at 2 yr of age. This is the first report of major vascular
      anomalies associated with goiter in any species. The mechanism is unknown.

PMID- 22611216
TI  - Cholesteatoma after lateral bulla osteotomy in two brachycephalic dogs.
AB  - This report describes a French bulldog and a pug that presented to the authors'
      hospital following total ear canal ablation (TECA) and lateral bulla osteotomy
      (LBO), with signs of recurring otitis media and difficulty opening their mouths.
      The bulldog also had unilateral facial paralysis and sensory deficits of the
      trigeminal nerve on the ipsilateral side. Computed tomography and MRI scans
      suggested cholesteatoma in the bulldog, but showed only slight enlargement of the
      bulla in the pug. Histopathologic examination of samples yielded cholesteatoma in
      both cases. The authors suspect that development of the cholesteatomas was linked
      to the TECA/LBO surgery in both cases. Cholesteatomas may occur more frequently
      than currently thought. Even if only slight changes of the bulla wall are
      detected on CT, early-stage cholesteatoma should be considered. The narrow
      anatomic conditions in brachycephalic dogs possibly predispose such breeds to
      develop cholesteatoma after middle ear surgery because complete removal of all
      inflammatory and epithelial tissue can be more difficult than in other breeds. To
      the authors' knowledge, this is the first report of an aural cholesteatoma
      causing sensory deficits of the trigeminal nerve.

PMID- 22611217
TI  - Clinical leptospirosis in three cats (2001-2009).
AB  - Based on previous research, cats were thought to have been resistant to the
      development of clinical signs following infection with Leptospira spp. This case
      report presents three confirmed, naturally infected clinical cases of feline
      leptospirosis. The cases presented were all indoor/outdoor cats that were known
      to hunt. They were also all presented at different stages of renal insufficiency;
      however, they did not show any liver involvement. The authors suggest that there
      may be a longer incubation period in cats than dogs and recommend further
      research in the form of a large, clinical study.

PMID- 22611219
TI  - Premenstrual syndrome.

PMID- 22611220
TI  - Classification of premenstrual disorders as proposed by the International Society
      for Premenstrual Disorders.
AB  - Premenstrual disorders have been recognized as affecting innumerable women for
      decades but unlike most other medical conditions universally accepted criteria
      for definition and diagnosis are not established. Although premenstrual syndrome
      (PMS) occurs throughout reproductive life, there are some women who become
      particularly troubled. Those approaching the menopause may also have a mixture of
      PMS and menopause symptoms, not to mention heavy periods. Furthermore, some of
      the symptoms are similar in nature and so it is a challenge to identify which set
      of symptoms belongs to which spectrum. This is an area that has not been explored
      well. Various classifications have been proposed over the last few decades. A
      further effort towards the classification was made by an international
      multidisciplinary group of experts established as the International Society for
      Premenstrual Disorders (ISPMD) in Montreal in September 2008. Their deliberations
      resulted in a unified diagnosis, classification of premenstrual disorders (PMD)
      along with their quantification and guidelines on clinical trial design. This
      classification of PMS is far more comprehensive and inclusive than previous
      attempts. PMD in the ISPMD Montreal consensus are divided into two categories:
      Core and Variant PMD. Core PMD are typical, pure or reference disorders
      associated with spontaneous ovulatory menstrual cycles while Variant PMD exist
      where more complex features are present. Further, the consensus group considered
      that PMD may be subdivided into three subgroups predominantly physical,
      predominantly psychological and mixed. Variant PMD encompass primarily four
      different types; premenstrual exacerbation, PMD with anovulatory ovarian
      activity, PMD with absent menstruation and progestogen-induced PMD.

PMID- 22611221
TI  - Epidemiology of premenstrual symptoms and disorders.
AB  - The aim of this paper is to review published literature on the types and
      prevalences of premenstrual disorders and symptoms, and effects of these on
      activities of daily life and other parameters of burden of illness. The method
      involved review of the pertinent published literature. Premenstrual disorders
      vary in prevalence according to the definition or categorization. The most severe
      disorder being premenstrual dysphoric disorder (PMDD) affects 3-8% of women of
      reproductive age. This disorder focuses on psychological symptoms whereas global
      studies show that the most prevalent premenstrual symptoms are physical. Both
      psychological and physical symptoms affect women's activities of daily life. A
      considerable burden of illness has been shown to be associated with moderate to
      severe premenstrual disorders. In conclusion, premenstrual symptoms are a
      frequent source of concern to women during their reproductive lives and moderate
      to severe symptoms impact on their quality of lives.

PMID- 22611222
TI  - Pathophysiology of premenstrual syndrome and premenstrual dysphoric disorder.
AB  - Premenstrual syndrome (PMS) and premenstrual dysphoric disorder are triggered by
      hormonal events ensuing after ovulation. The symptoms can begin in the early, mid
      or late luteal phase and are not associated with defined concentrations of any
      specific gonadal or non-gonadal hormone. Although evidence for a hormonal
      abnormality has not been established, the symptoms of the premenstrual disorders
      are related to the production of progesterone by the ovary. The two best-studied
      and relevant neurotransmitter systems implicated in the genesis of the symptoms
      are the GABArgic and the serotonergic systems. Metabolites of progesterone formed
      by the corpus luteum of the ovary and in the brain bind to a neurosteroid-binding
      site on the membrane of the gamma-aminobutyric acid (GABA) receptor, changing its
      configuration, rendering it resistant to further activation and finally
      decreasing central GABA-mediated inhibition. By a similar mechanism, the
      progestogens in some hormonal contraceptives are also thought to adversely affect
      the GABAergic system. The lowering of serotonin can give rise to PMS-like
      symptoms and serotonergic functioning seems to be deficient by some methods of
      estimating serotonergic activity in the brain; agents that augment serotonin are
      efficacious and are as effective even if administered only in the luteal phase.
      However, similar to the affective disorders, PMS is ultimately not likely to be
      related to the dysregulation of individual neurotransmitters. Brain imaging
      studies have begun to shed light on the complex brain circuitry underlying affect
      and behaviour and may help to explicate the intricate neurophysiological
      foundation of the syndrome.

PMID- 22611223
TI  - Psychotropic medications and other non-hormonal treatments for premenstrual
      disorders.
AB  - Selective serotonin re-uptake inhibitors have well-established efficacy for
      severe premenstrual syndrome and premenstrual dysphoric disorder. Efficacy has
      been reported with both continuous dosing (all cycle) and intermittent or luteal
      phase dosing (from ovulation to menses). Efficacy may be less with intermittent
      dosing, particularly for premenstrual physical symptoms. The efficacy of symptom
      onset dosing (medication taken only on luteal days when symptoms occur) needs
      further systematic study. Women going through the menopausal transition may need
      to adjust their antidepressant dosing regimen due to the change in frequency of
      menstruation. Anxiolytics, calcium, chasteberry and cognitive-behaviour therapy
      may also have a role in the treatment of premenstrual symptoms.

PMID- 22611224
TI  - Treatment of premenstrual disorders by suppression of ovulation by transdermal
      estrogens.
AB  - The understanding of the cause and treatment of premenstrual disorders is
      confused but it is essentially the result of cyclical ovarian activity, usually
      ovulation, and an effective treatment should be by suppressing ovulation. This
      can be done by an oral contraceptive but as these women are progestogen
      intolerant the symptoms may persist becoming constant rather than cyclical.
      Alternatively, transdermal estradiol by patch, gel or implant effectively removes
      the cyclical hormonal changes, which produce the cyclical symptoms. A shortened
      seven-day course of a progestogen is required each month for endometrial
      protection but it can reproduce premenstrual syndrome-type symptoms in these
      women. Gonadotropin-releasing hormone with 'add-back' is effective in the short
      term. Laparoscopic hysterectomy and bilateral oophorectomy with adequate
      replacement of estrogen and testosterone should be considered in the severe cases
      with progestogenic side-effects.

PMID- 22611225
TI  - Gonadotrophin receptor hormone analogues in combination with add-back therapy: an
      update.
AB  - Gonadotrophin receptor hormone analogues (GnRHa) have been used in a range of sex
      hormone-dependent disorders. In the management of premenstrual syndrome, they can
      completely abolish symptoms. The success of GnRHa in the treatment of
      endometriosis and adjuvant therapy in the management of fibroids is proven. This
      efficacy does not come without a cost and the side-effects of the hypo-estrogenic
      state have limited their application. The use of add-back therapy to counter
      these effects has enabled wider application, longer durations of treatment and an
      increase in compliance. This review article is an update on the evidence
      supporting gonadotrophin receptor hormone analogues in combination with add-back
      therapy.

PMID- 22611226
TI  - Potential strategies to avoid progestogen-induced premenstrual disorders.
AB  - Non-hormonal approaches to premenstrual syndrome (PMS) treatment such as
      selective serotonin reuptake inhibitors are by no means effective for all women
      and frequently we must resort to endocrine therapy. During many of the hormonal
      approaches, PMS-like symptoms can be introduced or re-introduced during the
      necessary cyclical or continuous progestogen component of the therapy. This is
      seen with combined oral contraception, progestogen only contraception,
      progestogen therapy for heavy menstrual bleeding and endometriosis, sequential
      hormone replacement therapy and any therapeutic strategy for premenstrual
      syndrome where it is necessary to provide endometrial protection, including
      estrogen suppression of ovulation or add-back during gonadotrophin releasing
      hormone suppression. The link to progestogen is very often missed by health
      professionals. When the pattern of symptoms mimics the cyclicity of PMS, it is
      termed progestogen-induced premenstrual disorder. The need to use progestogen to
      protect the endometrium from the proliferative actions of estrogen can pose
      insurmountable difficulties in managing premenstrual disorders. In the absence of
      any really useful evidence, nearly all practice in this area depends on clinician
      experience. We cannot afford to wait for adequate research evidence to be
      produced - it never will - and so we must rely on empirical findings, clinical
      experience, theoretical strategies and common sense.

PMID- 22611227
TI  - When should surgical treatment be considered for premenstrual dysphoric disorder?
AB  - Premenstrual mood disorders afflict a substantial number of women of reproductive
      age. Medical treatments provide excellent symptomatic relief to many women but at
      times a poor therapeutic response or adverse effects attributable to these
      therapies lead women to seek alternative solutions. Oophorectomy (with
      concomitant hysterectomy) followed by low-dose estrogen therapy has been shown to
      be an effective alternative for such cases of menstrual-cycle-related mood
      disorder.

PMID- 22611228
TI  - Severe premenstrual syndrome and bipolar disorder: a tragic confusion.
AB  - Bipolar disorder and severe premenstrual syndrome (PMS) have many symptoms in
      common, but it is important to establish the correct diagnosis between a severe
      psychiatric disorder and an endocrine disorder appropriately treatable with
      hormones. The measurement of hormone levels is not helpful in making this
      distinction, as they are all premenopausal women with normal follicle-stimulating
      hormone and estradiol levels. The diagnosis of PMS should come from the history
      relating the occurrence of cyclical mood and behaviour changes with menstruation,
      the improvement during pregnancy, postnatal depression and the presence of runs
      of many good days a month and the somatic symptoms of mastalgia, bloating and
      headaches. Young women with severe PMS do not respond to the antidepressants and
      mood-stabilizing drugs typically used for bipolar disorder.

PMID- 22611229
TI  - Menstruation and mental health: what's the chance of talking about that?

PMID- 22611230
TI  - Treatment of premenstrual syndrome: a decision-making algorithm.
AB  - The aim of this short paper will be to guide the clinician through the plethora
      of possible interventions to help them to individualize treatment for their
      patients with PMS. The discussion will highlight management principles rather
      than evidence per se. It uses as its basis an updated version of the treatment
      algorithm published by the RCOG in its Green Top Guideline no. 48 on the
      management of PMS.

PMID- 22611231
TI  - AhNRAMP1 iron transporter is involved in iron acquisition in peanut.
AB  - Peanut/maize intercropping is a sustainable and effective agroecosystem to
      alleviate iron-deficiency chlorosis. Using suppression subtractive hybridization
      from the roots of intercropped and monocropped peanut which show different iron
      nutrition levels, a peanut gene, AhNRAMP1, which belongs to divalent metal
      transporters of the natural resistance-associated macrophage protein (NRAMP) gene
      family was isolated. Yeast complementation assays suggested that AhNRAMP1 encodes
      a functional iron transporter. Moreover, the mRNA level of AhNRAMP1 was obviously
      induced by iron deficiency in both roots and leaves. Transient expression, laser
      microdissection, and in situ hybridization analyses revealed that AhNRAMP1 was
      mainly localized on the plasma membrane of the epidermis of peanut roots. Induced
      expression of AhNRAMP1 in tobacco conferred enhanced tolerance to iron
      deprivation. These results suggest that the AhNRAMP1 is possibly involved in iron
      acquisition in peanut plants.

PMID- 22611232
TI  - Early carbon mobilization and radicle protrusion in maize germination.
AB  - Considerable amounts of information is available on the complex carbohydrates
      that are mobilized and utilized by the seed to support early seedling
      development. These events occur after radicle has protruded from the seed.
      However, scarce information is available on the role of the endogenous soluble
      carbohydrates from the embryo in the first hours of germination. The present work
      analysed how the soluble carbohydrate reserves in isolated maize embryos are
      mobilized during 6-24 h of water imbibition, an interval that exclusively
      embraces the first two phases of the germination process. It was found that
      sucrose constitutes a very significant reserve in the scutellum and that it is
      efficiently consumed during the time in which the adjacent embryo axis is engaged
      in an active metabolism. Sucrose transporter was immunolocalized in the scutellum
      and in vascular elements. In parallel, a cell-wall invertase activity, which
      hydrolyses sucrose, developed in the embryo axis, which favoured higher glucose
      uptake. Sucrose and hexose transporters were active in the embryo tissues,
      together with the plasma membrane H(+)-ATPase, which was localized in all embryo
      regions involved in both nutrient transport and active cell elongation to support
      radicle extension. It is proposed that, during the initial maize germination
      phases, a net flow of sucrose takes place from the scutellum towards the embryo
      axis and regions that undergo elongation. During radicle extension, sucrose and
      hexose transporters, as well as H(+)-ATPase, become the fundamental proteins that
      orchestrate the transport of nutrients required for successful germination.

PMID- 22611234
TI  - Macrolide resistance testing and molecular subtyping of Treponema pallidum
      strains from southern Africa.
AB  - OBJECTIVES: To determine whether the 23S ribosomal RNA (rRNA) A2058G and A2059G
      mutations that confer macrolide resistance are present among southern African
      strains of Treponema pallidum and to determine their subtype distribution.
      METHODS: 117 genital ulcer specimens, collected between March 2005 and April 2010
      in South Africa and Lesotho and previously determined to be positive for T
      pallidum DNA by molecular testing, were retested using a commercial real-time PCR
      assay. Those specimens that were still positive for T pallidum DNA were screened
      for the macrolide resistance-encoding point mutations in the 23S rRNA gene using
      rapid PCR-based restriction digest assays. Molecular characterisation of two
      variable treponemal genes, arp and tpr, was used to subtype the T pallidum
      strains. RESULTS: 1 of 100 T pallidum-positive specimens, collected in Lesotho,
      contained the A2058G macrolide resistance-encoding 23S rRNA gene mutation,
      whereas the A2059G mutation was absent. It was possible to fully type 97/100 of
      all T pallidum DNA-positive samples. A total of nine arp repeat sizes, nine tpr
      patterns and a combined total of 20 subtypes were identified. Overall, the most
      common subtypes were 14d (32%), followed by 17d (12%), 14a (10%), 14b (8%), 22b
      (6%) and 14i (5%). Subtypes 14d and 14a were the predominant subtypes in samples
      from South Africa (43%) and Lesotho (22%), respectively. CONCLUSIONS: Macrolide
      resistance among T pallidum strains appears to be uncommon in southern Africa.
      Although a high degree of genetic heterogeneity was observed among the strains
      tested, T pallidum subtype 14d appears to be the predominant circulating strain.

PMID- 22611235
TI  - End-of-life vignette. Death by neurologic criteria.

PMID- 22611233
TI  - Comprehending crystalline beta-carotene accumulation by comparing engineered cell
      models and the natural carotenoid-rich system of citrus.
AB  - Genetic manipulation of carotenoid biosynthesis has become a recent focus for the
      alleviation of vitamin A deficiency. However, the genetically modified phenotypes
      often challenge the expectation, suggesting the incomplete comprehension of
      carotenogenesis. Here, embryogenic calli were engineered from four citrus
      genotypes as engineered cell models (ECMs) by over-expressing a bacterial
      phytoene synthase gene (CrtB). Ripe flavedos (the coloured outer layer of citrus
      fruits), which exhibit diverse natural carotenoid patterns, were offered as a
      comparative system to the ECMs. In the ECMs, carotenoid patterns showed diversity
      depending on the genotypes and produced additional carotenoids, such as lycopene,
      that were absent from the wild-type lines. Especially in the ECMs from dark-grown
      culture, there emerged a favoured beta,beta-pathway characterized by a striking
      accumulation of beta-carotene, which was dramatically different from those in the
      wild-type calli and ripe flavedos. Unlike flavedos that contained a typical
      chromoplast development, the ECMs sequestered most carotenoids in the amyloplasts
      in crystal form, which led the amyloplast morphology to show a chromoplast-like
      profile. Transcriptional analysis revealed a markedly flavedo-specific expression
      of the beta-carotene hydroxylase gene (HYD), which was suppressed in the calli.
      Co-expression of CrtB and HYD in the ECMs confirmed that HYD predominantly
      mediated the preferred carotenoid patterns between the ECMs and flavedos, and
      also revealed that the carotenoid crystals in the ECMs were mainly composed of
      beta-carotene. In addition, a model is proposed to interpret the common
      appearance of a favoured beta,beta-pathway and the likelihood of carotenoid
      degradation potentially mediated by photo-oxidation and vacuolar phagocytosis in
      the ECMs is discussed.

PMID- 22611236
TI  - Grief experiences of 3 caregiving wives of veterans with dementia.
AB  - Three wives share their experiences of caregiving for husbands with dementia. The
      3 husbands, aged 51, 71, and 84, developed dementia following years of devoted
      military service. To present lived experiences of caregiving wives', meanings
      attributed to caregiving are investigated, variations in caregiving and grieving
      experiences are explored, and therapeutic implications are offered. Through case
      study approach and with issues of caregiver grief considered, we introduce life
      course and ambiguous loss theoretical perspectives. Emergent qualitative themes
      and quantitative inventory ratings indicate significant differences in caregiver
      grief response depend on care-recipient age. Practice implications and directions
      for future care recipient, age-related research are presented.

PMID- 22611238
TI  - Innate IFNs and plasmacytoid dendritic cells constrain Th2 cytokine responses to
      rhinovirus: a regulatory mechanism with relevance to asthma.
AB  - Human rhinoviruses (RV) cause only minor illness in healthy individuals, but can
      have deleterious consequences in people with asthma. This study sought to examine
      normal homeostatic mechanisms regulating adaptive immunity to RV in healthy
      humans, focusing on effects of IFN-alphabeta and plasmacytoid dendritic cells
      (pDC) on Th2 immune responses. PBMC were isolated from 27 healthy individuals and
      cultured with RV16 for up to 5 d. In some experiments, IFN-alphabeta was
      neutralized using a decoy receptor that blocks IFN signaling, whereas specific
      dendritic cell subsets were depleted from cultures with immune-magnetic beads.
      RV16 induced robust expression of IFN-alpha, IFN-beta, multiple IFN-stimulated
      genes, and T cell-polarizing factors within the first 24 h. At 5 d, the
      production of memory T cell-derived IFN-gamma, IL-10, and IL-13, but not IL-17A,
      was significantly elevated. Neutralizing the effects of type-I IFN with the decoy
      receptor B18R led to a significant increase in IL-13 synthesis, but had no effect
      on IFN-gamma synthesis. Depletion of pDC from RV-stimulated cultures markedly
      inhibited IFN-alpha secretion, and led to a significant increase in expression
      and production of the Th2 cytokines IL-5 (p = 0.02), IL-9 (p < 0.01), and IL-13
      (p < 0.01), but had no effect on IFN-gamma synthesis. Depletion of CD1c(+)
      dendritic cells did not alter cytokine synthesis. In healthy humans, pDC and the
      IFN-alphabeta they secrete selectively constrain Th2 cytokine synthesis following
      RV exposure in vitro. This important regulatory mechanism may be lost in asthma;
      deficient IFN-alphabeta synthesis and/or pDC dysfunction have the potential to
      contribute to asthma exacerbations during RV infections.

PMID- 22611237
TI  - A p53 axis regulates B cell receptor-triggered, innate immune system-driven B
      cell clonal expansion.
AB  - Resting mature human B cells undergo a dynamic process of clonal expansion,
      followed by clonal contraction, during an in vitro response to surrogate C3d
      coated Ag and innate immune system cytokines, IL-4 and BAFF. In this study, we
      explore the mechanism for clonal contraction through following the time- and
      division-influenced expression of several pro- and anti-apoptotic proteins within
      CFSE-labeled cultures. Several findings, involving both human and mouse B cells,
      show that a mitochondria-dependent apoptotic pathway involving p53 contributes to
      the high activation-induced cell death (AICD) susceptibility of replicating
      blasts. Activated B cell clones exhibit elevated p53 protein and elevated
      mRNA/protein of proapoptotic molecules known to be under direct p53
      transcriptional control, Bax, Bad, Puma, Bid, and procaspase 6, accompanied by
      reduced anti-apoptotic Bcl-2. Under these conditions, Bim levels were not
      increased. The finding that full-length Bid protein significantly declines in
      AICD-susceptible replicating blasts, whereas Bid mRNA does not, suggests that Bid
      is actively cleaved to short-lived, proapoptotic truncated Bid. AICD was
      diminished, albeit not eliminated, by p53 small interfering RNA transfection,
      genetic deletion of p53, or Bcl-2 overexpression. DNA damage is a likely trigger
      for p53-dependent AICD because susceptible lymphoblasts expressed significantly
      elevated levels of both phosphorylated ataxia telangiectasia mutated-Ser(1980)
      and phospho-H2AX-Ser(139). Deficiency in activation-induced cytosine deaminase
      diminishes but does not ablate murine B cell AICD, indicating that activation
      induced cytosine deaminase-induced DNA damage is only in part responsible.
      Evidence for p53-influenced AICD during this route of T cell-independent clonal
      expansion raises the possibility that progeny bearing p53 mutations might undergo
      positive selection in peripherally inflamed tissues with elevated levels of IL-4
      and BAFF.

PMID- 22611239
TI  - CXCL17 is a mucosal chemokine elevated in idiopathic pulmonary fibrosis that
      exhibits broad antimicrobial activity.
AB  - The mucosal immune network is a crucial barrier preventing pathogens from
      entering the body. The network of immune cells that mediates the defensive
      mechanisms in the mucosa is likely shaped by chemokines, which attract a wide
      range of immune cells to specific sites of the body. Chemokines have been divided
      into homeostatic or inflammatory depending upon their expression patterns.
      Additionally, several chemokines mediate direct killing of invading pathogens, as
      exemplified by CCL28, a mucosa-associated chemokine that exhibits antimicrobial
      activity against a range of pathogens. CXCL17 was the last chemokine ligand to be
      described and is the 17th member of the CXC chemokine family. Its expression
      pattern in 105 human tissues and cells indicates that CXCL17 is a homeostatic,
      mucosa-associated chemokine. Its strategic expression in mucosal tissues suggests
      that it is involved in innate immunity and/or sterility of the mucosa. To test
      the latter hypothesis, we tested CXCL17 for possible antibacterial activity
      against a panel of pathogenic and opportunistic bacteria. Our results indicate
      that CXCL17 has potent antimicrobial activities and that its mechanism of
      antimicrobial action involves peptide-mediated bacterial membrane disruption.
      Because CXCL17 is strongly expressed in bronchi, we measured it in
      bronchoalveolar lavage fluids and observed that it is strongly upregulated in
      idiopathic pulmonary fibrosis. We conclude that CXCL17 is an antimicrobial
      mucosal chemokine that may play a role in the pathogenesis of interstitial lung
      diseases.

PMID- 22611240
TI  - Magnesium decreases inflammatory cytokine production: a novel innate
      immunomodulatory mechanism.
AB  - MgSO(4) exposure before preterm birth is neuroprotective, reducing the risk of
      cerebral palsy and major motor dysfunction. Neonatal inflammatory cytokine levels
      correlate with neurologic outcome, leading us to assess the effect of MgSO(4) on
      cytokine production in humans. We found reduced maternal TNF-alpha and IL-6
      production following in vivo MgSO(4) treatment. Short-term exposure to a
      clinically effective MgSO(4) concentration in vitro substantially reduced the
      frequency of neonatal monocytes producing TNF-alpha and IL-6 under constitutive
      and TLR-stimulated conditions, decreasing cytokine gene and protein expression,
      without influencing cell viability or phagocytic function. In summary, MgSO(4)
      reduced cytokine production in intrapartum women, term and preterm neonates,
      demonstrating effectiveness in those at risk for inflammation-associated adverse
      perinatal outcomes. By probing the mechanism of decreased cytokine production, we
      found that the immunomodulatory effect was mediated by magnesium and not the
      sulfate moiety, and it was reversible. Cellular magnesium content increased
      rapidly upon MgSO(4) exposure, and reduced cytokine production occurred following
      stimulation with different TLR ligands as well as when magnesium was added after
      TLR stimulation, strongly suggesting that magnesium acts intracellularly.
      Magnesium increased basal IKBalpha levels, and upon TLR stimulation was
      associated with reduced NF-kappaB activation and nuclear localization. These
      findings establish a new paradigm for innate immunoregulation, whereby magnesium
      plays a critical regulatory role in NF-kappaB activation, cytokine production,
      and disease pathogenesis.

PMID- 22611242
TI  - Cutting edge: Evidence for a dynamically driven T cell signaling mechanism.
AB  - T cells use the alphabeta TCR to bind peptides presented by MHC proteins (pMHC)
      on APCs. Formation of a TCR-pMHC complex initiates T cell signaling via a poorly
      understood process, potentially involving changes in oligomeric state, altered
      interactions with CD3 subunits, and mechanical stress. These mechanisms could be
      facilitated by binding-induced changes in the TCR, but the nature and extent of
      any such alterations are unclear. Using hydrogen/deuterium exchange, we
      demonstrate that ligation globally rigidifies the TCR, which via entropic and
      packing effects will promote associations with neighboring proteins and enhance
      the stability of existing complexes. TCR regions implicated in lateral
      associations and signaling are particularly affected. Computational modeling
      demonstrated a high degree of dynamic coupling between the TCR constant and
      variable domains that is dampened upon ligation. These results raise the
      possibility that TCR triggering could involve a dynamically driven, allosteric
      mechanism.

PMID- 22611241
TI  - Pten loss in CD4 T cells enhances their helper function but does not lead to
      autoimmunity or lymphoma.
AB  - PTEN, one of the most commonly mutated or lost tumor suppressors in human
      cancers, antagonizes signaling by the PI3K pathway. Mice with thymocyte-specific
      deletion of Pten rapidly develop peripheral lymphomas and autoimmunity, which may
      be caused by failed negative selection of thymocytes or from dysregulation of
      postthymic T cells. We induced conditional deletion of Pten from CD4 Th cells
      using a Cre knocked into the Tnfrsf4 (OX40) locus to generate OX40(Cre)Pten(f)
      mice. Pten-deficient Th cells proliferated more and produced greater
      concentrations of cytokines. The OX40(Cre)Pten(f) mice had a general increase in
      the number of lymphocytes in the lymph nodes, but not in the spleen. When
      transferred into wild-type (WT) mice, Pten-deficient Th cells enhanced anti
      Listeria responses and the clearance of tumors under conditions in which WT T
      cells had no effect. Moreover, inflammatory responses were exaggerated and
      resolved later in OX40(Cre)Pten(f) mice than in WT mice. However, in contrast
      with models of thymocyte-specific Pten deletion, lymphomas and autoimmunity were
      not observed, even in older OX40(Cre)Pten(f) mice. Hence loss of Pten enhances Th
      cell function without obvious deleterious effects.

PMID- 22611243
TI  - Signal-transducing adaptor protein-2 modulates Fas-mediated T cell apoptosis by
      interacting with caspase-8.
AB  - We found that an adaptor protein, signal-transducing adaptor protein (STAP)-2, is
      a new member of the Fas-death-inducing signaling complex and participates in
      activation-induced cell death in T cells. STAP-2 enhanced Fas-mediated apoptosis
      and caspase-8 aggregation and activation in Jurkat T cells. Importantly, STAP-2
      directly interacted with caspase-8 and Fas, resulting in enhanced interactions
      between caspase-8 and FADD in the Fas-death-inducing signaling complex. Moreover,
      STAP-2 protein has a consensus caspase-8 cleavage sequence, VEAD, in its C
      terminal domain, and processing of STAP-2 by caspase-8 was crucial for Fas
      induced apoptosis. Physiologic roles of STAP-2 were confirmed by observations
      that STAP-2-deficient mice displayed impaired activation-induced cell death and
      superantigen-induced T cell depletion. Therefore, STAP-2 is a novel participant
      in the regulation of T cell apoptosis after stimulation.

PMID- 22611244
TI  - Development of mature and functional human myeloid subsets in hematopoietic stem
      cell-engrafted NOD/SCID/IL2rgammaKO mice.
AB  - Although physiological development of human lymphoid subsets has become well
      documented in humanized mice, in vivo development of human myeloid subsets in a
      xenotransplantation setting has remained unevaluated. Therefore, we investigated
      in vivo differentiation and function of human myeloid subsets in
      NOD/SCID/IL2rgamma(null) (NSG) mouse recipients transplanted with purified
      lineage(-)CD34(+)CD38(-) cord blood hematopoietic stem cells. At 4-6 mo
      posttransplantation, we identified the development of human neutrophils,
      basophils, mast cells, monocytes, and conventional and plasmacytoid dendritic
      cells in the recipient hematopoietic organs. The tissue distribution and
      morphology of these human myeloid cells were similar to those identified in
      humans. After cytokine stimulation in vitro, phosphorylation of STAT molecules
      was observed in neutrophils and monocytes. In vivo administration of human G-CSF
      resulted in the recruitment of human myeloid cells into the recipient
      circulation. Flow cytometry and confocal imaging demonstrated that human bone
      marrow monocytes and alveolar macrophages in the recipients displayed intact
      phagocytic function. Human bone marrow-derived monocytes/macrophages were further
      confirmed to exhibit phagocytosis and killing of Salmonella typhimurium upon IFN
      gamma stimulation. These findings demonstrate the development of mature and
      functionally intact human myeloid subsets in vivo in the NSG recipients. In vivo
      human myelopoiesis established in the NSG humanized mouse system may facilitate
      the investigation of human myeloid cell biology including in vivo analyses of
      infectious diseases and therapeutic interventions.

PMID- 22611245
TI  - Comment on "Cutting edge: regulatory T cells do not mediate suppression via
      programmed cell death pathways".

PMID- 22611246
TI  - Comment on "Frequency of epitope-specific naive CD4+ T cells correlates with
      immunodominance in the human memory repertoire".

PMID- 22611247
TI  - How discovery of Toll-mediated innate immunity in Drosophila impacted our
      understanding of TLR signaling (and vice versa).

PMID- 22611248
TI  - Pillars article: the dorsoventral regulatory gene cassette spatzle/Toll/cactus
      controls the potent antifungal response in Drosophila adults. Cell. 1996. 86: 973
      983.
AB  - The cytokine-induced activation cascade of NF-kappaB in mammals and the
      activation of the morphogen dorsal in Drosophila embryos show striking structural
      and functional similarities (Toll/IL-1, Cactus/I-kappaB, and dorsal/NF-kappaB).
      Here we demonstrate that these parallels extend to the immune response of
      Drosophila. In particular, the intracellular components of the dorsoventral
      signaling pathway (except for dorsal) and the extracellular Toll ligand, spatzle
      regulatory gene cassette, control expression of the antifungal peptide gene
      drosomycin in adults. We also show that mutations in the Toll signaling pathway
      dramatically reduce survival after fungal infection. Antibacterial genes are
      induced either by a distinct pathway involving the immune deficiency gene (imd)
      or by combined activation of both imd and dorsoventral pathways.

PMID- 22611249
TI  - Retraction: CD226 expression deficiency causes high sensitivity to apoptosis in
      NK T cells from patients with systemic lupus erythematosus.

PMID- 22611250
TI  - Retraction: Valpha24-invariant NKT cells from patients with allergic asthma
      express CCR9 at high frequency and induce Th2 bias of CD3+ T cells upon CD226
      engagement.

PMID- 22611251
TI  - Immunization against proprotein convertase subtilisin-like/kexin type 9 lowers
      plasma LDL-cholesterol levels in mice.
AB  - Successful development of drugs against novel targets crucially depends on
      reliable identification of the activity of the target gene product in vivo and a
      clear demonstration of its specific functional role for disease development.
      Here, we describe an immunological knockdown (IKD) method, a novel approach for
      the in vivo validation and functional study of endogenous gene products. This
      method relies on the ability to elicit a transient humoral response against the
      selected endogenous target protein. Anti-target antibodies specifically bind to
      the target protein and a fraction of them effectively neutralize its activity. We
      applied the IKD method to the in vivo validation of plasma PCSK9 as a potential
      target for the treatment of elevated levels of plasma LDL-cholesterol. We show
      that immunization with human-PCSK9 in mice is able to raise antibodies that cross
      react and neutralize circulating mouse-PCSK9 protein thus resulting in increased
      liver LDL receptor levels and plasma cholesterol uptake. These findings closely
      resemble those described in PCSK9 knockout mice or in mice treated with
      antibodies that inhibit PCSK9 by preventing the PCSK9/LDLR interaction. Our data
      support the IKD approach as an effective method to the rapid validation of new
      target proteins.

PMID- 22611252
TI  - USP2a negatively regulates IL-1beta- and virus-induced NF-kappaB activation by
      deubiquitinating TRAF6.
AB  - The transcription factor NF-kappaB plays critical roles in many biological
      processes, especially immunity. The signaling to NF-kappaB activation is subtly
      regulated to avoid harmful immune effects. In this report, we identified
      ubiquitin-specific protease 2 isoform a (USP2a) as a novel negative regulator in
      Toll-like receptors/IL-1beta- and Sendai virus (SeV)-induced NF-kappaB
      activation. Overexpression of USP2a inhibited IL-1beta- and SeV-induced NF-kappaB
      activation and transcription of inflammatory cytokines, whereas the knockdown or
      knockout of USP2a had opposite effects. USP2a-deficient cells exhibited
      potentiated ubiquitination of tumor necrosis factor receptor-associated factor 6
      (TRAF6) upon stimulation by IL-1beta and SeV. Furthermore, USP2a was
      constitutively associated with TRAF6, and removed K63-linked polyubiquitin chains
      of TRAF6 induced by IL-1beta and SeV stimulation. The residues of USP2a important
      for their role were also identified. Because of the importance of TRAF6 in
      multiple pathways leading to NF-kappaB activation, these findings provide a
      general regulatory mechanism for NF-kappaB activation triggered by different
      stimuli.

PMID- 22611253
TI  - Age- and diet-dependent requirement of DJ-1 for glucose homeostasis in mice with
      implications for human type 2 diabetes.
AB  - Elderly patients often suffer from multiple age-related diseases. Here we show
      that the expression of DJ-1, an antioxidant protein with reduced expression in
      the central nervous system of patients with Parkinson's disease, is reduced in
      pancreatic islets of patients with type 2 diabetes mellitus (T2DM). In contrast,
      under non-diabetic conditions, DJ-1 expression increases in mouse and human
      islets during aging. In mouse islets, we show that DJ-1 prevents an increase in
      reactive oxygen species levels as the mice age. This antioxidant function
      preserves mitochondrial integrity and physiology, prerequisites for glucose
      stimulated insulin secretion. Accordingly, DJ-1-deficient mice develop glucose
      intolerance and reduced beta cell area as they age or gain weight. Our data
      suggest that DJ-1 is more generally involved in age- and lifestyle-related human
      diseases and show for the first time that DJ-1 plays a key role in glucose
      homeostasis and might serve as a novel drug target for T2DM.

PMID- 22611254
TI  - Evidence-based assessment of PET in Germany.

PMID- 22611255
TI  - Coronary calcium score as an adjunct to nuclear myocardial perfusion imaging for
      risk stratification before noncardiac surgery.
AB  - The purpose of this study was to evaluate the added value of coronary artery
      calcium score (CACS) as an adjunct to myocardial perfusion imaging (MPI) with
      SPECT for cardiac risk stratification before noncardiac surgery. SPECT MPI is a
      well-established and widely used tool for preoperative risk stratification before
      noncardiac surgery. The potential added value of combining SPECT MPI with CACS is
      unknown. METHODS: We included 326 consecutive patients who were referred for
      SPECT MPI for preoperative cardiac risk assessment before elective noncardiac
      surgery. All patients underwent an additional low-dose CT scan for CACS and SPECT
      MPI. Patients were followed up for 40 d after their index surgical procedure, and
      the occurrence of major adverse cardiovascular events (MACE), including death,
      myocardial infarction, revascularization, stroke, and sudden cardiac death, was
      registered. RESULTS: Postoperative MACE occurred in 30 patients (9%). Cumulative
      MACE rate was highest in patients with abnormal SPECT and high CACS (22%),
      defined by a cutoff value CACS of 1,314 or more, and lowest in patients with
      normal SPECT MPI findings and low CACS (5%) (CACS < 1,314). A CACS score of 1,314
      or more was independently associated with a higher MACE rate in patients with
      normal (12% vs. 5%) or abnormal perfusion (22% vs. 12%, P < 0.05 for all
      intergroup comparisons). CONCLUSION: SPECT MPI findings and CACS are strong
      preoperative risk predictors. CACS allows further risk stratification, indicating
      very low risk when CACS less than 1,314 is associated with normal SPECT MPI
      findings. Conversely, in patients with abnormal SPECT MPI findings, a CACS of
      1,314 or more confers an added value for predicting adverse outcomes.

PMID- 22611256
TI  - Evidence-based assessment of PET in Germany.

PMID- 22611258
TI  - Restructured endoplasmic reticulum generated by mutant amyotrophic lateral
      sclerosis-linked VAPB is cleared by the proteasome.
AB  - VAPB (vesicle-associated membrane protein-associated protein B) is a ubiquitously
      expressed, ER-resident tail-anchored protein that functions as adaptor for lipid
      exchange proteins. Its mutant form, P56S-VAPB, is linked to a dominantly
      inherited form of amyotrophic lateral sclerosis (ALS8). P56S-VAPB forms
      intracellular inclusions, whose role in ALS pathogenesis has not yet been
      elucidated. We recently demonstrated that these inclusions are formed by
      profoundly remodelled stacked ER cisternae. Here, we used stable HeLa-TetOff cell
      lines inducibly expressing wild-type VAPB and P56S-VAPB, as well as
      microinjection protocols in non-transfected cells, to investigate the dynamics of
      inclusion generation and degradation. Shortly after synthesis, the mutant protein
      forms small, polyubiquitinated clusters, which then congregate in the
      juxtanuclear region independently of the integrity of the microtubule
      cytoskeleton. The rate of degradation of the aggregated mutant is higher than
      that of the wild-type protein, so that the inclusions are cleared only a few
      hours after cessation of P56S-VAPB synthesis. At variance with other inclusion
      bodies linked to neurodegenerative diseases, clearance of P56S-VAPB inclusions
      involves the proteasome, with no apparent participation of macro-autophagy.
      Transfection of a dominant-negative form of the AAA ATPase p97/VCP stabilizes
      mutant VAPB, suggesting a role for this ATPase in extracting the aggregated
      protein from the inclusions. Our results demonstrate that the structures induced
      by P56S-VAPB stand apart from other inclusion bodies, both in the mechanism of
      their genesis and of their clearance from the cell, with possible implications
      for the pathogenic mechanism of the mutant protein.

PMID- 22611259
TI  - Arf6 negatively controls the rapid recycling of the beta2 adrenergic receptor.
AB  - beta2-adrenergic receptor (beta2AR), a member of the GPCR (G-protein coupled
      receptor) family, is internalized in a ligand- and beta-arrestin-dependent manner
      into early endosomes, and subsequently recycled back to the plasma membrane.
      Here, we report that beta-arrestin promotes the activation of the small G protein
      Arf6, which regulates the recycling and degradation of beta2AR. We demonstrate in
      vitro that the C-terminal region of beta-arrestin1 interacts directly and
      simultaneously with Arf6GDP and its specific exchange factor EFA6, to promote
      Arf6 activation. Similarly, the ligand-mediated activation of beta2AR leads to
      the formation of Arf6GTP in vivo in a beta-arrestin-dependent manner. Expression
      of either EFA6 or an activated Arf6 mutant caused accumulation of beta2AR in the
      degradation pathway. This phenotype could be rescued by the expression of an
      activated mutant of Rab4, suggesting that Arf6 acts upstream of Rab4. We propose
      a model in which Arf6 plays an essential role in beta2AR desensitization. The
      ligand-mediated stimulation of beta2AR relocates beta-arrestin to the plasma
      membrane, and triggers the activation of Arf6 by EFA6. The activation of Arf6
      leads to accumulation of beta2AR in the degradation pathway, and negatively
      controls Rab4-dependent fast recycling to prevent the re-sensitization of
      beta2AR.

PMID- 22611261
TI  - The effect of a vaccination program on child anthropometry: evidence from India's
      Universal Immunization Program.
AB  - BACKGROUND: Childhood vaccination may protect children's nutritional status and
      lead to improved child growth in developing countries. This study evaluates the
      effect of India's childhood vaccination program Universal Immunization Program
      (UIP) on the growth of children <4 years of age. METHODS: Regression models were
      estimated to examine the effect of UIP on vaccination status and children's
      anthropometric outcomes, as well as to test whether UIP's effect was uniform
      across various subpopulations of Indian children. RESULTS: UIP increased height
      for-age and weight-for-age among children. This effect constituted a 22-25%
      reduction in the height-for-age deficit and a 15% reduction in the weight-for-age
      deficit of the average child. The program appears to have had no effect on other
      anthropometric indicators or vaccination status. UIP also led to differential
      changes in anthropometry and vaccination status, based on differences in wealth,
      maternal education and scheduled-caste status. CONCLUSIONS: UIP led to improved
      child growth. This suggests that vaccination programs-in addition to being a
      major intervention for reducing child mortality-might be considered a tool for
      mitigating undernutrition in developing countries. This study also adds to the
      growing evidence that childhood vaccination programs are high-return investments
      because they produce long-term health benefits for children.

PMID- 22611262
TI  - 'McDonalds and KFC, it's never going to happen': the challenges of working with
      food outlets to tackle the obesogenic environment.
AB  - BACKGROUND: Food outlets may make an important contribution to an obesogenic
      environment. This study investigated barriers and facilitators to public health
      work with food outlets in disadvantaged areas. METHODS: In-depth qualitative
      interviews with 36 directors, managers and public health service delivery staff
      in a coterminous primary care trust and local authority in northwest England.
      Data were analysed using the constant comparative method. RESULTS: Three
      interventions were available to engage with businesses; awards for premises that
      welcomed breastfeeding mothers or offered healthy menu options and local
      authority planning powers. Sensitivity to the potential conflict between
      activities that generate profit and those that promote health, led to
      compromises, such as awards for cafes that offer only one healthy option on an
      otherwise unhealthy menu. An absence of existing relationships with businesses
      and limited time were powerful disincentives to action, leading to greater
      engagement with public rather than private sector organizations. Hiring staff
      with commercial experience and incentives for businesses were identified as
      useful strategies, but seldom used. CONCLUSIONS: Encouraging food outlets to
      contribute to tackling the obesogenic environment is a major challenge for local
      public health teams that requires supportive national policies. Commitment to
      engage with the local public health service should be part of any national
      voluntary agreements with industry.

PMID- 22611263
TI  - Weight loss from three commercial providers of NHS primary care slimming on
      referral in North Somerset: service evaluation.
AB  - BACKGROUND: The aim of this study was to analyse the effect of provider, gender
      and obesity class on outcomes of National Health Service (NHS) slimming on
      referral. METHODS: Service evaluation in 12 UK general practices. Obese patients
      aged >=16 were referred for 12 sessions to one of three commercial providers.
      Outcomes at 12 weeks were attendance, BMI, total and percentage weight loss, 5%
      and 5 kg weight loss and comparison across providers. Linear and multiple
      regression analyses were used, adjusting for confounders. RESULTS: One thousand
      four hundred and forty patients were referred; 1047 receiving vouchers and 880
      attending at least one session. The mean weight change was -4.8 kg (95% CI: -5.1
      to -4.5) and the percentage bodyweight loss was -4.6% (standard deviation: 3.7).
      Weight Watchers patients lost more weight [-1.15 kg (95% confidence interval, CI:
      -1.25, -1.04), P < 0.001] and were more likely to lose 5% bodyweight [odds ratio:
      1.81 (95% CI: 1.78, 1.83), P < 0.001] than those attending the provider with the
      least weight loss. CONCLUSIONS: NHS slimming on referral can successfully achieve
      short-term weight loss. Patients attending Weight Watchers were most likely to
      lose weight than those attendingother providers.

PMID- 22611264
TI  - Comment on Richardson's Investing in public health: barriers and possible
      solutions.

PMID- 22611265
TI  - Needs-based education in the context of globalization.

PMID- 22611266
TI  - Immunization training: right or privilege?

PMID- 22611267
TI  - Building a multi-institutional community of practice to foster assessment.
AB  - This paper discusses the development of a multi-institutional community of
      practice that formed over 5 years. This community of practice was intentionally
      designed to support the evolution of student learning and programmatic assessment
      within member colleges and schools. Critical phases to the community's
      development are outlined, as well as its mission and goals. In addition, the
      community's contributions to faculty development and the scholarship of
      assessment are detailed. Success factors are discussed to assist others who may
      wish to initiate assessment-related collaborations across institutional borders.
      The community's vision for the future is also outlined.

PMID- 22611268
TI  - Pharmacy practice department chairs' perspectives on part-time faculty members.
AB  - OBJECTIVE: To identify the benefits and consequences of having part-time faculty
      members in departments of pharmacy practice from the department chair's
      perspective. METHODS: A stratified purposive sample of 12 pharmacy practice
      department chairs was selected. Eleven telephone interviews were conducted. Two
      investigators independently read interview notes and categorized and enumerated
      responses to determine major themes using content analysis. The investigators
      jointly reviewed the data and came to consensus on major themes. RESULTS:
      Benefits of allowing full-time faculty members to reduce their position to part
      time included faculty retention and improved individual faculty work/life
      balance. Consequences of allowing part-time faculty positions included the
      challenges of managing individual and departmental workloads, the risk of
      marginalizing part-time faculty members, and the challenges of promotion and
      tenure issues. All requests to switch to part-time status were faculty-driven and
      most were approved. CONCLUSIONS: There are a variety of benefits and consequences
      of having part-time faculty in pharmacy practice departments from the chair's
      perspective. Clear faculty and departmental expectations of part-time faculty
      members need to be established to ensure optimal success of this working
      arrangement.

PMID- 22611269
TI  - A summer pharmacy camp for high school students as a pharmacy student recruitment
      tool.
AB  - OBJECTIVE: To determine the effectiveness of a summer pharmacy camp on
      participants' pursuit of enrollment in doctor of pharmacy degree programs.
      METHODS: All participants (n = 135) in a pharmacy camp at the University of
      Arkansas for Medical Sciences (UAMS) College of Pharmacy from 2007-2010 were
      invited to complete an anonymous online survey instrument. RESULTS: Seventy-three
      students completed the survey instrument (54% response rate). Ninety-six percent
      of pharmacy camp participants said that they would recommend pharmacy camp to a
      friend, and 76% planned to apply or had applied to doctor of pharmacy degree
      program. Seven of the camp participants had enrolled in the UAMS College of
      Pharmacy. CONCLUSIONS: The pharmacy summer camp at UAMS is effective in
      maintaining high school students' interest in the profession of pharmacy.
      Continued use of the pharmacy camp program as a recruitment tool is warranted;
      however, additional research on this topic is needed.

PMID- 22611270
TI  - Follow-up assessment of a faculty peer observation and evaluation program.
AB  - OBJECTIVE: To assess a previously described peer observation and evaluation
      program 2 years after implementation. METHODS: An pre-implementation survey
      assessed faculty needs and attitudes related to peer evaluation. Two years after
      implementation, the survey was repeated and additional questions asked regarding
      adherence to peer observation and evaluation policies and procedures, feedback
      received, and impact on teaching. RESULTS: Faculty attitudes towards peer
      evaluation stayed the same or improved post-implementation. Adherence to the
      initial 3 steps of the process was high (100%, 100%, and 94%, respectively);
      however, step 4, which required a final discussion after student assessments were
      finished, was completed by only 47% of the respondents. All faculty members
      reported receiving a balance of positive and constructive feedback; 78% agreed
      that peer observation and evaluation gave them concrete suggestions for improving
      their teaching; and 89% felt that the benefits of peer observation and evaluation
      outweighed the effort of participating. CONCLUSIONS: Faculty members adhered to
      the policies and procedures of peer observation and evaluation and found peer
      feedback was beneficial.

PMID- 22611271
TI  - Pharmacy students' perceptions of and attitudes towards peer assessment within a
      drug literature evaluation course.
AB  - OBJECTIVE: To assess pharmacy students' perceptions of and attitudes towards the
      use of peer assessment within a drug literature evaluation course. METHODS: A 15
      item, electronic survey instrument was sent to 158 second-year pharmacy students
      enrolled in a 2-credit required literature evaluation course at the Purdue
      University College of Pharmacy. RESULTS: One hundred fifty-two (96.2%) responses
      were received. Approximately 95% of students agreed that they had the necessary
      skills to assess their peers and 91.8% agreed that their peers possessed these
      skills as well. More students agreed they were comfortable receiving feedback
      from peers (95.7%) than agreed they were comfortable providing feedback to peers
      (80%). The majority of students (91.9%) agreed that peer assessment was a skill
      they will use in their career as a pharmacist. CONCLUSION: Students were more
      comfortable receiving feedback from peers than providing peer assessment. This
      skill is used by pharmacists throughout their career; therefore, students should
      become familiar and comfortable with the peer assessment process.

PMID- 22611272
TI  - Comparison of pharmacy students' perceived and actual knowledge using the
      Pharmacy Curricular Outcomes Assessment.
AB  - OBJECTIVE: To determine whether a correlation exists between third-year PharmD
      students' perceived pharmacy knowledge and actual pharmacy knowledge as assessed
      by the Pharmacy Curricular Outcomes Assessment (PCOA). METHODS: In 2010 and 2011,
      the PCOA was administered in a low-stakes environment to third-year pharmacy
      students at North Dakota State University College of Pharmacy, Nursing, and
      Allied Sciences (COPNAS). A survey instrument was also administered on which
      students self-assessed their perceived competencies in each of the core areas
      covered by the PCOA examination. RESULTS: The pharmacy students rated their
      competencies slightly higher than average. Performance on the PCOA was similar to
      but slightly higher than national averages. Correlations between each of the 4
      content areas (basic biomedical sciences, pharmaceutical sciences,
      social/administrative sciences, and clinical sciences) mirrored those reported
      nationally by the National Association of Boards of Pharmacy (NABP). Student
      performance on the basic biomedical sciences portion of the PCOA was
      significantly correlated with students' perceived competencies in the biomedical
      sciences. No other correlations between actual and perceived competencies were
      significant. CONCLUSION: A lack of correlation exists between what students
      perceive they know and what they actually know in the areas of pharmaceutical
      science; social, behavioral, and administrative science; and clinical science.
      Therefore, additional standardized measures are needed to assess curricular
      effectiveness and provide comparisons among pharmacy programs.

PMID- 22611273
TI  - Availability and perceived value of masters of business administration degree
      programs in pharmaceutical marketing and management.
AB  - OBJECTIVES: To examine pharmacist-targeted master of business administration
      (MBA) degree programs and investigate pharmacists' perceptions regarding them.
      METHODS: Specialized MBA programs in pharmaceutical marketing and management
      offered at US colleges and schools of pharmacy were identified in the literature
      and compared. Pharmacists' perceptions of MBA programs were evaluated through a
      survey of clinical preceptors affiliated with a school of pharmacy. RESULTS:
      Seven US universities that offer an MBA program in pharmaceutical marketing and
      management were identified. Thirty-three percent of the 57 pharmacist preceptors
      who responded to the survey reported plans to pursue an MBA degree program.
      Respondents preferred MBA programs related to healthcare or pharmacy (66%) over
      general MBA programs (33%). CONCLUSION: An MBA in pharmaceutical marketing and
      management could provide pharmacists with advanced knowledge of the operational
      and strategic business aspects of pharmacy practice and give pharmacy graduates
      an advantage in an increasingly competitive job market.

PMID- 22611274
TI  - Achievement goal orientation and situational motivation for a low-stakes test of
      content knowledge.
AB  - OBJECTIVE: To determine the extent of the relationship between students' inherent
      motivation to achieve in a doctor of pharmacy program and their motivation to
      achieve on a single low-stakes test of content knowledge. METHOD: The Attitude
      Toward Learning Questionnaire (ATL) was administered to 66 third-year pharmacy
      students at the beginning of the spring 2011 semester, and the Student Opinion
      Scale (SOS) was administered to the same group immediately following completion
      of the Pharmacy Curricular Outcomes Assessment (PCOA). RESULTS: Significant
      differences were found in performance approach and work avoidance based on
      situational motivation scores. Situational motivation was also found to be
      directly correlated with performance and mastery approaches and inversely
      correlated with work avoidance. Criteria were met for predicting importance and
      effort from performance and mastery approaches and work avoidance scores of
      pharmacy students. CONCLUSIONS: The ability to predict pharmacy students'
      motivation to perform on a low-stakes standardized test of content knowledge
      increases the test's usefulness as a measure of curricular effectiveness.

PMID- 22611275
TI  - Use of high-fidelity simulation to teach end-of-life care to pharmacy students in
      an interdisciplinary course.
AB  - OBJECTIVE: To assess the effect of high-fidelity simulation on pharmacy students'
      attitudes and perceived competencies in providing end-of-life care in an
      interdisciplinary palliative care course. DESIGN: Thirty pharmacy students
      participated in a high-fidelity simulation of the 15 minutes before and 15
      minutes after the death of a patient with end-stage renal disease. ASSESSMENT:
      Students completed the Attitudes Toward Death Survey and the End of Life
      Competency Survey prior to and after experiencing the simulation. A reflections
      journal exercise was used to capture post-simulation subjective reactions, and a
      course evaluation was used to assess students' satisfaction with the simulation
      experience. Students' post-simulation attitudes toward death significantly
      improved compared to pre-simulation attitudes and they felt significantly more
      competent to take care of dying patients. Students were satisfied with this
      teaching method. CONCLUSION: High-fidelity simulation is an innovative way to
      challenge pharmacy students' attitudes and help them with knowledge acquisition
      about end-of-life care.

PMID- 22611276
TI  - Evaluation of pharmacotherapy laboratory revisions implemented to reduce cost.
AB  - OBJECTIVES: To revise a pharmacotherapy-laboratory curriculum to decrease course
      expenditures while maintaining a quality educational experience. DESIGN: Course
      mapping identified laboratory activities that achieved the defined learning
      outcomes. Redundant activities were eliminated, and remaining activities not
      requiring active in-laboratory participation were converted into prelaboratory
      assignments and simulations. An online course-management system provided a
      platform for simulations and automated grading. ASSESSMENT: An evaluation of
      economic data showed a 64% and 43% decrease in total course expenditures for
      Pharmacotherapy Laboratory III and IV, respectively. Although a comparison of
      examination and course grades before and after redesign revealed a small decrease
      in grades for the Pharmacotherapy III and IV course, the reasons for this
      decrease were unclear and could not be directly attributed to the redesign.
      Comparison of students' evaluation scores before and after the redesign showed
      continued high satisfaction with the course. CONCLUSIONS: Revisions made to the
      curriculum for a pharmacotherapy laboratory decreased course expenditures while
      maintaining the quality of education. The successful redesign was related to
      several key components including course mapping and enhanced use of technology. A
      similar revision process can be considered by other colleges and schools of
      pharmacy facing budgetary reductions.

PMID- 22611277
TI  - Use of SMART learning objectives to introduce continuing professional development
      into the pharmacy curriculum.
AB  - OBJECTIVE: To determine whether a 2-year continuing professional development
      (CPD) training program improved first-year (P1) and second-year (P2) pharmacy
      students' ability to write SMART (specific, measurable, achievable, relevant, and
      timed) learning objectives. DESIGN: First-year students completed live or online
      CPD training, including creating portfolios and writing SMART objectives prior to
      their summer introductory pharmacy practice experience (IPPE). In year 2, P1 and
      P2 students were included. SMART learning objectives were graded and analyzed.
      ASSESSMENT: On several objectives, the 2011 P1 students (n = 130) scored higher
      than did the P2 cohort (n = 105). In 2011, P2 students outscored their own
      performance in 2010. In 2011, P1 students who had been trained in online modules
      performed the same as did live-session trainees with respect to SMART objectives.
      CONCLUSION: With focused online or live training, students are capable of
      incorporating principles of CPD by writing SMART learning objectives.

PMID- 22611278
TI  - Use of online modules to enhance knowledge and skills application during an
      introductory pharmacy practice experience.
AB  - OBJECTIVES: To implement and assess the effectiveness of online instructional
      modules to increase the consistency of learning outcomes related to students'
      patient-care practice knowledge and their skills application and confidence
      across introductory pharmacy practice experience (IPPE) sites. DESIGN: Twenty
      online modules were created to provide uniform delivery of instructional content
      that complemented classroom instruction and to introduce students to common
      pharmacy-practice skills in the patient-care arena. ASSESSMENT: Quantitative data
      were collected by means of a survey and pre- and post-module quizzes, which were
      completed by students to assess knowledge. More than 85% of students applied the
      IPPE skills. During the course, students' confidence increased significantly in
      all areas. For all but 1 of the 13 competencies, more than 70% of students agreed
      or strongly agreed that the competencies were met. CONCLUSIONS: Online
      instructional modules in patient care can effectively increase students'
      knowledge, skills application, and confidence, and improve the consistency of
      achieving outcomes for instructional content and activities across diverse
      practice settings.

PMID- 22611279
TI  - A Spanish language module in a first-year pharmaceutical care laboratory course.
AB  - OBJECTIVE: To assess the impact of incorporating Spanish language lectures and
      activities in a required Pharmaceutical Care Laboratory course on first-year
      doctor of pharmacy (PharmD) students' perceptions of and comfort level with
      Spanish-speaking patients and basic knowledge of Spanish pharmacy terms. DESIGN:
      The 6-week module consisted of attendance at a 1-hour lecture on medical Spanish
      and Hispanic culture, and completion of 4 small-group activities: drug and
      product information, patient information, counseling and side effects, and a
      written scenario that involved filling a prescription for and counseling a
      Spanish-speaking patient. ASSESSMENT: All students enrolled in the Pharmaceutical
      Care Laboratory course in fall 2008 (153) and fall 2009 (152) completed a pre-
      and post-intervention questionnaire (100% response rate). Less than 4% of
      students considered themselves fluent in Spanish prior to participating in the
      Spanish language module. Students agreed or strongly agreed that it was important
      for pharmacists to be able to translate common pharmacy label instructions from
      English to Spanish (89.8%) and Spanish to English (73.8%). Student-reported
      confidence in their ability to pronounce common pharmacy and medical terms in
      Spanish significantly increased, as did their ability to correctly interpret
      pharmacy label instructions. CONCLUSIONS: While incorporation of a Spanish
      language module in a first-year Pharmaceutical Care Laboratory course did not
      result in students achieving fluency in Spanish, it was a beneficial method of
      exposing students to Spanish language and culture.

PMID- 22611280
TI  - An interprofessional course using human patient simulation to teach patient
      safety and teamwork skills.
AB  - OBJECTIVES: To assess the effectiveness of human patient simulation to teach
      patient safety, team-building skills, and the value of interprofessional
      collaboration to pharmacy students. DESIGN: Five scenarios simulating semi-urgent
      situations that required interprofessional collaboration were developed. Groups
      of 10 to 12 health professions students that included 1 to 2 pharmacy students
      evaluated patients while addressing patient safety hazards. ASSESSMENT: Pharmacy
      students' scores on 8 of 30 items on a post-simulation survey of knowledge,
      skills, and attitudes improved over pre-simulation scores. Students' scores on 3
      of 10 items on a team building and interprofessional communications survey also
      improved after participating in the simulation exercise. Over 90% of students
      reported that simulation increased their understanding of professional roles and
      the importance of interprofessional communication. CONCLUSIONS: Simulation
      training provided an opportunity to improve pharmacy students' ability to
      recognize and react to patient safety concerns and enhanced their
      interprofessional collaboration and communication skills.

PMID- 22611281
TI  - Professionalism in pharmacy: a continual societal and intellectual challenge.

PMID- 22611282
TI  - The art of student facilitation: does patient counseling technique have a role?

PMID- 22611283
TI  - The Effect of Education on Old Age Cognitive Abilities: Evidence from a
      Regression Discontinuity Design.
AB  - In this paper we exploit the 1947 change to the minimum school-leaving age in
      England from 14 to 15, to evaluate the causal effect of a year of education on
      cognitive abilities at older ages. We use a regression discontinuity design
      analysis and find a large and significant effect of the reform on males' memory
      and executive functioning at older ages, using simple cognitive tests from the
      English Longitudinal Survey on Ageing (ELSA) as our outcome measures. This result
      is particularly remarkable since the reform had a powerful and immediate effect
      on about half the population of 14-year-olds. We investigate and discuss the
      potential channels by which this reform may have had its effects, as well as
      carrying out a full set of sensitivity analyses and robustness checks.

PMID- 22611284
TI  - Modeling and numerical simulation of blood flow using the Theory of Interacting
      Continua.
AB  - In this paper we use a modified form of the mixture theory developed by Massoudi
      and Rajagopal to study the blood flow in a simple geometry, namely flow between
      two plates. The blood is assumed to behave as a two-component mixture comprised
      of plasma and red blood cells (RBCs). The plasma is assumed to behave as a
      viscous fluid whereas the RBCs are given a granular-like structure where the
      viscosity also depends on the shear-rate.

PMID- 22611285
TI  - Re-Examining the Case for Marriage: Union Formation and Changes in Well-Being.
AB  - This article addresses open questions about the nature and meaning of the
      positive association between marriage and well-being, namely, the extent to which
      it is causal, shared with cohabitation, and stable over time. We relied on data
      from the National Survey of Families and Households (N = 2,737) and a modeling
      approach that controls for fixed differences between individuals by relating
      union transitions to changes in well-being. This study is unique in examining the
      persistence of changes in well-being as marriages and cohabitations progress (and
      potentially dissolve) over time. The effects of marriage and cohabitation are
      found to be similar across a range of measures tapping psychological well-being,
      health, and social ties. Where there are statistically significant differences,
      marriage is not always more advantageous. Overall, differences tend to be small
      and appear to dissipate over time, even when the greater instability of
      cohabitation is taken into account.

PMID- 22611286
TI  - Fitting In: The Roles of Social Acceptance and Discrimination in Shaping the
      Academic Motivations of Latino Youth in the U.S. Southeast.
AB  - Using data on 459 Latino 9(th) graders from the LA-SIAA and the NC-SIAA studies,
      we evaluate the specific educational values and beliefs that motivate the
      academic achievement of Latino youth and contrast the school experiences of
      Latino youth in an emerging Latino community, North Carolina, with the school
      experiences of youth living in a traditional settlement community, Los Angeles.
      Despite their greater fears of discrimination, we find that Latino youth in North
      Carolina are more academically motivated than their peers in Los Angeles. This is
      partially because they are more likely to be immigrants. Being an immigrant,
      having a stronger sense of ethnic identification, and having a stronger sense of
      family obligation were each linked to a more positive view of school
      environments. Therefore, these factors each partially explained the immigrant
      advantage in academic motivation and helped to counter the harmful effects of
      discrimination on academic motivation.

PMID- 22611288
TI  - Globe to globe: whither (local) public health?

PMID- 22611287
TI  - Ancestral Plasticity and Allometry in Threespine Stickleback Fish Reveal
      Phenotypes Associated with Derived, Freshwater Ecotypes.
AB  - For over a century, evolutionary biologists have debated whether and how
      phenotypic plasticity impacts the processes of adaptation and diversification.
      The empirical tests required to resolve these issues have proven elusive, mainly
      because it requires documentation of ancestral reaction norms, a difficult
      prospect where many ancestors are either extinct or have evolved. The threespine
      stickleback radiation is not limited in this regard, making it an ideal system in
      which to address general questions regarding the role of plasticity in adaptive
      evolution. As retreating ice sheets have exposed new habitats, oceanic
      stickleback founded innumerable freshwater populations, many of which have
      evolved parallel adaptations to their new environments. Because the founding
      oceanic population is extant, we can directly evaluate whether specific patterns
      of ancestral phenotypic expression in the context of novel environments
      (plasticity), or over ontogeny, predisposed the repeated evolution of "benthic"
      and "limnetic" ecotypes in shallow and deep lakes, respectively. Consistent with
      this hypothesis, we found that oceanic stickleback raised in a complex habitat
      and fed a macroinvertebrate diet expressed traits resembling derived, benthic
      fish. Alternatively, when reared in a simple environment on a diet of
      zooplankton, oceanic stickleback developed phenotypes resembling derived,
      limnetic fish. As fish in both treatments grew, their body depths increased
      allometrically, as did the size of their mouths, while their eyes became
      relatively smaller. Allometric trajectories were subtly but significantly
      impacted by rearing environment. Thus, both environmental and allometric
      influences on development, along with their interactive effects, produced
      variation in phenotypes consistent with derived benthic and limnetic fish, which
      may have predisposed the repeated genetic accommodation of this specific suite of
      traits. We also found significant shape differences between marine and anadromous
      stickleback, which has implications for evaluating the ancestral state of
      stickleback traits.

PMID- 22611289
TI  - Tracking and understanding the utility of Cochrane reviews for public health
      decision-making.

PMID- 22611290
TI  - NICE public health guidance update.

PMID- 22611291
TI  - Competitive Food Sales in Schools and Childhood Obesity: A Longitudinal Study.
AB  - The vast majority of American middle schools and high schools sell what is known
      as "competitive foods", such as soft drinks, candy bars, and chips, to children.
      The relationship between consumption of sugar-sweetened drinks and snacks and
      childhood obesity is well established but it remains unknown whether competitive
      food sales in schools are related to unhealthy weight gain among children. We
      examined this association using data from the Early Childhood Longitudinal Study
      Kindergarten Cohort. Employing fixed effects models and a natural experimental
      approach, we found that children's weight gain between 5(th) and 8(th) grades was
      not associated with the introduction or the duration of exposure to competitive
      food sales in middle school. Also, the relationship between competitive foods and
      weight gain did not vary significantly by gender, race/ethnicity, or family SES,
      and remained weak and insignificant across several alternative model
      specifications. One possible explanation is that children's food preferences and
      dietary patterns are firmly established before adolescence. Also, middle school
      environments may dampen the effects of competitive food sales because they so
      highly structure children's time and eating opportunities.

PMID- 22611292
TI  - Cyclization of peptoids by formation of boronate esters.
AB  - Introduction of conformational constraints into peptoids (N-substituted
      oligoglycines) will enable new applications in molecular recognition and self
      assembly. Peptoids that contain both a phenylboronic acid side chain and a
      vicinal diol cyclize by intramolecular condensation to form boronate esters. A
      fluorescent indicator of free boronic acid was used to assay esterification. A
      galactose moiety 2 to 5 monomer units away from a boronic acid side chain in a
      peptoid reacts with the boronic acid in competition with the indicator. The
      intramolecular reaction predominates in each case, with 80-90% of the peptoid
      cyclized. When the diol is a simple 2,3-dihydroxypropyl group, esterification is
      less favored but still appreciable.

PMID- 22611293
TI  - The production and phonetic representation of fake geminates in English.
AB  - The current study focused on the production of non-contrastive geminates across
      different boundary types in English to investigate the hypothesis that word
      internal heteromorphemic geminates may differ from those that arise across a word
      boundary. In this study, word-internal geminates arising from affixation, and
      described as either assimilated or concatenated, were matched to heteromorphemic
      geminates arising from sequences of identical consonants that spanned a word
      boundary and to word-internal singletons. Word-internal geminates were found to
      be longer than matched singletons in absolute and relative terms. By contrast,
      heteromorphemic geminates that occurred at word boundaries were only longer than
      matched singletons in absolute terms. In addition, heteromorphemic geminates in
      two word phrases were typically "pulled apart" in careful speech; that is,
      speakers marked the boundaries between free morphemes with pitch changes and
      pauses. Morpheme boundaries in words with bound affixes were very rarely
      highlighted in this way. These results are taken to indicate that most word
      internal heteromorphemic geminates are represented as a single long consonant in
      the speech plan rather than as a consonant sequence. Only those geminates that
      arise in two word phrases exhibit phonetic characteristics that are fully
      consistent with the representation of two identical consonants crossing a
      morpheme boundary.

PMID- 22611294
TI  - On the age-independent publication index.
AB  - It is shown that the age-independent index based on h-type index per decade,
      called hereafter an alpha index instead of the a index, suggested by Kosmulski
      (Journal of Informetrics 3, 341-347, 2009) and Abt (Scientometrics 2012) is
      related to the square-root of the ratio of citation acceleration a to the Hirsch
      constant A.

PMID- 22611295
TI  - What compound words mean to children with specific language impairment.
AB  - Sixteen children (17 age mates, 17 vocabulary mates) with specific language
      impairment (SLI) participated in two studies. In the first, they named fantasy
      objects. All groups coined novel noun-noun compounds on a majority of trials but
      only the SLI group had difficulty ordering the nouns as dictated by semantic
      context. In the second study, the children described the meaning of conventional
      noun-noun compounds. The SLI and AM groups did not differ in parsing the nouns,
      but the SLI group was poorer at explaining the semantic relationships between
      them. Compared to vocabulary mates, a larger proportion of the SLI group
      successfully parsed the compounds but a smaller proportion could explain them.
      These difficulties may reflect problems in the development of links within the
      semantic lexicon.

PMID- 22611296
TI  - A mass spectrometry proteomics data management platform.
AB  - Mass spectrometry-based proteomics is increasingly being used in biomedical
      research. These experiments typically generate a large volume of highly complex
      data, and the volume and complexity are only increasing with time. There exist
      many software pipelines for analyzing these data (each typically with its own
      file formats), and as technology improves, these file formats change and new
      formats are developed. Files produced from these myriad software programs may
      accumulate on hard disks or tape drives over time, with older files being
      rendered progressively more obsolete and unusable with each successive technical
      advancement and data format change. Although initiatives exist to standardize the
      file formats used in proteomics, they do not address the core failings of a file
      based data management system: (1) files are typically poorly annotated
      experimentally, (2) files are "organically" distributed across laboratory file
      systems in an ad hoc manner, (3) files formats become obsolete, and (4) searching
      the data and comparing and contrasting results across separate experiments is
      very inefficient (if possible at all). Here we present a relational database
      architecture and accompanying web application dubbed Mass Spectrometry Data
      Platform that is designed to address the failings of the file-based mass
      spectrometry data management approach. The database is designed such that the
      output of disparate software pipelines may be imported into a core set of unified
      tables, with these core tables being extended to support data generated by
      specific pipelines. Because the data are unified, they may be queried, viewed,
      and compared across multiple experiments using a common web interface. Mass
      Spectrometry Data Platform is open source and freely available at
      http://code.google.com/p/msdapl/.

PMID- 22611297
TI  - High-throughput DNA methylation datasets for evaluating false discovery rate
      methodologies.
AB  - When analyzing high-throughput genomic data, the multiple comparison problem is
      most often addressed through estimation of the false discovery rate (FDR), using
      methods such as the Benjamini & Hochberg, Benjamini & Yekutieli, the q-value
      method, or in controlling the family-wise error rate (FWER) using Holm's step
      down method. To date, research studies that have compared various FDR/FWER
      methodologies have made use of limited simulation studies and/or have applied the
      methods to one or more microarray gene expression dataset(s). However, for
      microarray datasets the veracity of each null hypothesis tested is unknown so
      that an objective evaluation of performance cannot be rendered for application
      data. Due to the role of methylation in X-chromosome inactivation, we postulate
      that high-throughput methylation datasets may provide an appropriate forum for
      assessing the performance of commonly used FDR methodologies. These datasets
      preserve the complex correlation structure between probes, offering an advantage
      over simulated datasets. Using several methylation datasets, commonly used FDR
      methods including the q-value, Benjamini & Hochberg, and Benjamini & Yekutieli
      procedures as well as Holm's step down method were applied to identify CpG sites
      that are differentially methylated when comparing healthy males to healthy
      females. The methods were compared with respect to their ability to identify CpG
      sites located on sex chromosomes as significant, by reporting the sensitivity,
      specificity, and observed FDR. These datasets are useful for characterizing the
      performance of multiple comparison procedures, and may find further utility in
      other tasks such as comparing variable selection capabilities of classification
      methods and evaluating the performance of meta-analytic methods for microarray
      data.

PMID- 22611298
TI  - A Longitudinal Study of the Relation Between Depressive Symptomatology and
      Parenting Practices.
AB  - This longitudinal study examined whether mothers' depressive symptomatology
      predicted parenting practices in a sample of 199 mothers of 3-year-old children
      with behavior problems who were assessed yearly until age 6. Higher maternal
      depressive symptoms were associated with higher overreactivity and laxness and
      lower warmth when children were 6 years old. Higher maternal depressive symptoms
      were also related to increases in overreactivity across the preschool years.
      Moreover, depression and parenting practices (overreactivity and laxness)
      covaried over time within mothers. These results provide evidence of a strong
      link between maternal depression and parenting during the preschool years.

PMID- 22611299
TI  - Psychological Well-being in Fathers of Adolescents and Young Adults with Down
      Syndrome, Fragile X Syndrome, and Autism.
AB  - The psychological well-being of fathers of children with developmental
      disabilities remains poorly understood. The present study examined depressive
      symptoms, pessimism, and coping in fathers of adolescents and young adults with
      Down syndrome (DS; n = 59), autism spectrum disorders (ASDs; n = 135), and
      fragile X syndrome (FXS; n = 46) Fathers of sons/daughters with ASDs reported a
      higher level of depressive symptoms than the other groups of fathers. Fathers of
      sons/daughters with DS reported a lower level of pessimism than the other groups
      of fathers. There were no group differences in paternal coping style. Group
      differences in paternal depressive symptoms and pessimism were, in part, related
      to differences in paternal age, the child's behavior problems, risk of having
      additional children with a disability, and maternal depressive symptoms. Findings
      from this study can be used to educate providers and design services for fathers
      during the later parenting years.

PMID- 22611300
TI  - Correlates of Quality of Life in New Migrants to Hong Kong from Mainland China.
AB  - The concept of Quality of life (QOL) has received considerable attention from
      different disciplines. The aim of this study was to identify what are the
      correlates of QOL among Chinese new immigrants in Hong Kong. Data were collected
      through a cross-sectional survey among 449 Hong Kong new immigrants from Mainland
      China. Bivariate and multiple regression analyses were performed to examine the
      association between immigrants' QOL and their demographic characteristics, socio
      economic factors, optimism, sense of control, perceived social support, perceived
      neighborhood disorder, collective efficacy, pre-migration planning, depressive
      symptoms and acculturation stress. Our findings demonstrated that depressive
      symptom is the most prominent factor in reducing immigrants' level of QOL,
      perceived social support and optimism are the two important factors that enhance
      the QOL of these depressed immigrants. Our results indicate that preventive
      measures must be developed, and professional counseling and psychological support
      services must be provided to new immigrants in Hong Kong, especially those who
      have depressive symptoms.

PMID- 22611301
TI  - Preferences for Professional Assistance for Distress in a Diverse Sample of Older
      Adults.
AB  - Older adults (N=140; 68.6% minority) participating in community health screenings
      reported their use and preferences for various professionals and services to deal
      with distress. Race/ethnicity was recorded based on self-report. A third of
      participants had discussed distress with some professional within the past year.
      Compared to Whites, Asian and Black elders were less likely to see a mental
      health professional or receive counseling in the past year. Almost all
      participants (89.3%) were willing to discuss distress with some professional;
      most preferred medical (37.9%) or religious professionals (21.4%). Fewer Asians
      expressed willingness across most professionals and services. Findings support
      efforts to integrate mental health with other services, and suggest the need for
      additional strategies to enhance willingness to use mental health services,
      especially for Asian elders.

PMID- 22611302
TI  - Disengagement and Engagement Coping with HIV/AIDS Stigma and Psychological Well
      Being of People with HIV/AIDS.
AB  - The stigma associated with HIV/AIDS poses a psychological challenge to people
      living with HIV/AIDS. We hypothesized that that the consequences of stigma
      related stressors on psychological well-being would depend on how people cope
      with the stress of HIV/AIDS stigma. Two hundred participants with HIV/AIDS
      completed a self-report measure of enacted stigma and felt stigma, a measure of
      how they coped with HIV/AIDS stigma, and measures of depression and anxiety, and
      self-esteem. In general, increases in felt stigma (concerns with public
      attitudes, negative self-image, and disclosure concerns) coupled with how
      participants reported coping with stigma (by disengaging from or engaging with
      the stigma stressor) predicted self-reported depression, anxiety, and self
      esteem. Increases in felt stigma were associated with increases in anxiety and
      depression among participants who reported relatively high levels of
      disengagement coping compared to participants who reported relatively low levels
      of disengagement coping. Increases in felt stigma were associated with decreased
      self-esteem, but this association was attenuated among participants who reported
      relatively high levels of engagement control coping. The data also suggested a
      trend that increases in enacted stigma predicted increases in anxiety, but not
      depression, among participants who reported using more disengagement coping.
      Mental health professionals working with people who are HIV positive should
      consider how their clients cope with HIV/AIDS stigma and consider tailoring
      current therapies to address the relationship between stigma, coping, and
      psychological well-being.

PMID- 22611303
TI  - A structured vocabulary for indexing dietary supplements in databases in the
      United States.
AB  - Food composition databases are critical to assess and plan dietary intakes.
      Dietary supplement databases are also needed because dietary supplements make
      significant contributions to total nutrient intakes. However, no uniform system
      exists for classifying dietary supplement products and indexing their ingredients
      in such databases. Differing approaches to classifying these products make it
      difficult to retrieve or link information effectively. A consistent approach to
      classifying information within food composition databases led to the development
      of LanguaLTM, a structured vocabulary. LanguaLTM is being adapted as an interface
      tool for classifying and retrieving product information in dietary supplement
      databases. This paper outlines proposed changes to the LanguaLTM thesaurus for
      indexing dietary supplement products and ingredients in databases. The choice of
      12 of the original 14 LanguaLTM facets pertinent to dietary supplements,
      modifications to their scopes, and applications are described. The 12 chosen
      facets are: Product Type; Source; Part of Source; Physical State, Shape or Form;
      Ingredients; Preservation Method, Packing Medium, Container or Wrapping; Contact
      Surface; Consumer Group/Dietary Use/Label Claim; Geographic Places and Regions;
      and Adjunct Characteristics of food.

PMID- 22611304
TI  - Trait Self-esteem Moderates Decreases in Self-control Following Rejection: An
      Information-processing Account.
AB  - In the current paper, the authors posit that trait self-esteem moderates the
      relationship between social rejection and decrements in self-control, propose an
      information-processing account of trait self-esteem's moderating influence and
      discuss three tests of this theory. The authors measured trait self-esteem,
      experimentally manipulated social rejection and assessed subsequent self-control
      in Studies 1 and 2. Additionally, Study 3 framed a self-control task as
      diagnostic of social skills to examine motivational influences. Together, the
      results reveal that rejection impairs self-control, but only among low self
      esteem individuals. Moreover, this decrement in self-control only emerged when
      the task had no social implications-suggesting that low self-esteem individuals
      exert effort on tasks of social value and are otherwise preoccupied with
      belonging needs when completing nonsocial tasks.

PMID- 22611305
TI  - In situ Synthesis of Oligonucleotide Arrays on Surfaces Coated with Crosslinked
      Polymer Multilayers.
AB  - We report an approach to the in situ synthesis of oligonucleotide arrays on
      surfaces coated with crosslinked polymer multilayers. Our approach makes use of
      methods for the 'reactive' layer-by-layer assembly of thin, amine-reactive
      multilayers using branched polyethyleneimine (PEI) and the azlactone
      functionalized polymer poly(2-vinyl-4,4'-dimethylazlactone) (PVDMA). Post
      fabrication treatment of film-coated glass substrates with d-glucamine or 4-amino
      1-butanol yielded hydroxyl-functionalized films suitable for the Maskless Array
      Synthesis (MAS) of oligonucleotide arrays. Glucamine-functionalized films yielded
      arrays of oligonucleotides with fluorescence intensities and signal-to-noise
      ratios (after hybridization with fluorescently labeled complementary strands)
      comparable to those of arrays fabricated on conventional silanized glass
      substrates. These arrays could be exposed to multiple hybridization
      dehybridization cycles with only moderate loss of hybridization density. The
      versatility of the layer-by-layer approach also permitted synthesis directly on
      thin sheets of film-coated poly(ethylene terephthalate) (PET) to yield flexible
      oligonucleotide arrays that could be readily manipulated (e.g., bent) and cut
      into smaller arrays. To our knowledge, this work presents the first use of
      polymer multilayers as a substrate for the multi-step synthesis of complex
      molecules. Our results demonstrate that these films are robust and able to
      withstand the ~450 individual chemical processing steps associated with MAS (as
      well as manipulations required to hybridize, image, and dehybridize the arrays)
      without large-scale cracking, peeling, or delamination of the thin films. The
      combination of layer-by-layer assembly and MAS provides a means of fabricating
      functional oligonucleotide arrays on a range of different materials and
      substrates. This approach may also prove useful for the fabrication of supports
      for the solid-phase synthesis and screening of other macromolecular or small
      molecule agents.

PMID- 22611306
TI  - Dissonance-Based Interventions for Substance Using Alternative High-School Youth.
AB  - This article describes an innovative new intervention tailored to older youth who
      are already abusing drugs, but who are not diagnostically ready for treatment.
      The basic tenet of this intervention is to utilize adolescents engaged in drug
      use as "experts" in the prevention curriculum adaptation activity. This activity
      then serves as a mechanism for their dissonance-based change. This process is
      designed to intervene with drug abusing youth prior to their development of
      substance dependence. The community-based design grew from a United States
      federally funded NIDA project (National Institute of Drug Abuse Mentored Research
      Scientist Award) which found that the youth who conduct program adaptations were
      effectively engaged, animatedly discussing the payoffs and downsides of drug and
      alcohol abuse. It is maintained through this research that dissonance between
      their role of "Preventionist" and their own substance abuse behaviors lead to
      shifts in attitudes and behaviors. Dissonance-based interventions (DBIs) have
      been successfully utilized for positive behavioral change with a variety of
      disorders, but have not yet been implemented with substance abusing youth.
      Findings of pilot research are shared along with implications for future research
      and interventions.

PMID- 22611307
TI  - Pathogenesis of NSAID-induced gastric damage: importance of cyclooxygenase
      inhibition and gastric hypermotility.
AB  - This article reviews the pathogenic mechanism of non-steroidal anti-inflammatory
      drug (NSAID)-induced gastric damage, focusing on the relation between
      cyclooxygenase (COX) inhibition and various functional events. NSAIDs, such as
      indomethacin, at a dose that inhibits prostaglandin (PG) production, enhance
      gastric motility, resulting in an increase in mucosal permeability, neutrophil
      infiltration and oxyradical production, and eventually producing gastric lesions.
      These lesions are prevented by pretreatment with PGE2 and antisecretory drugs,
      and also via an atropine-sensitive mechanism, not related to antisecretory
      action. Although neither rofecoxib (a selective COX-2 inhibitor) nor SC-560 (a
      selective COX-1 inhibitor) alone damages the stomach, the combined administration
      of these drugs provokes gastric lesions. SC-560, but not rofecoxib, decreases
      prostaglandin E2 (PGE2) production and causes gastric hypermotility and an
      increase in mucosal permeability. COX-2 mRNA is expressed in the stomach after
      administration of indomethacin and SC-560 but not rofecoxib. The up-regulation of
      indomethacin-induced COX-2 expression is prevented by atropine at a dose that
      inhibits gastric hypermotility. In addition, selective COX-2 inhibitors have
      deleterious influences on the stomach when COX-2 is overexpressed under various
      conditions, including adrenalectomy, arthritis, and Helicobacter pylori
      infection. In summary, gastric hypermotility plays a primary role in the
      pathogenesis of NSAID-induced gastric damage, and the response, causally related
      with PG deficiency due to COX-1 inhibition, occurs prior to other pathogenic
      events such as increased mucosal permeability; and the ulcerogenic properties of
      NSAIDs require the inhibition of both COX-1 and COX-2, the inhibition of COX-1
      upregulates COX-2 expression in association with gastric hypermotility, and PGs
      produced by COX-2 counteract the deleterious effect of COX-1 inhibition.

PMID- 22611308
TI  - Clopidogrel and proton pump inhibitors--where do we stand in 2012?
AB  - Clopidogrel in association with aspirine is considered state of the art of
      medical treatment for acute coronary syndrome by reducing the risk of new
      ischemic events. Concomitant treatment with proton pump inhibitors in order to
      prevent gastrointestinal side effects is recommended by clinical guidelines.
      Clopidogrel needs metabolic activation predominantly by the hepatic cytochrome
      P450 isoenzyme Cytochrome 2C19 (CYP2C19) and proton pump inhibitors (PPIs) are
      extensively metabolized by the CYP2C19 isoenzyme as well. Several pharmacodynamic
      studies investigating a potential clopidogrel-PPI interaction found a significant
      decrease of the clopidogrel platelet antiaggregation effect for omeprazole, but
      not for pantoprazole. Initial clinical cohort studies in 2009 reported an
      increased risk for adverse cardiovascular events, when under clopidogrel and PPI
      treatment at the same time. These observations led the United States Food and
      Drug Administration and the European Medecines Agency to discourage the
      combination of clopidogrel and PPI (especially omeprazole) in the same year. In
      contrast, more recent retrospective cohort studies including propensity score
      matching and the only existing randomized trial have not shown any difference
      concerning adverse cardiovascular events when concomitantly on clopidogrel and
      PPI or only on clopidogrel. Three meta-analyses report an inverse correlation
      between clopidogrel-PPI interaction and study quality, with high and moderate
      quality studies not reporting any association, rising concern about unmeasured
      confounders biasing the low quality studies. Thus, no definite evidence exists
      for an effect on mortality. Because PPI induced risk reduction clearly overweighs
      the possible adverse cardiovascular risk in patients with high risk of
      gastrointestinal bleeding, combination of clopidogrel with the less CYP2C19
      inhibiting pantoprazole should be recommended.

PMID- 22611309
TI  - Enhanced apoptosis in post-liver transplant hepatitis C: effects of virus and
      immunosuppressants.
AB  - Hepatitis C (HCV)-infected patients have a poorer survival post-liver
      transplantation compared to patients transplanted for other indications, since
      HCV recurrence post-transplant is universal and commonly follows an aggressive
      course. There is increasing evidence that in the non-transplant setting,
      induction of hepatocyte apoptosis is one of the main mechanisms by which HCV
      drives liver inflammation and fibrosis, and that HCV proteins directly promote
      apoptosis. Recent studies have shown that post-liver transplant, there is a link
      between high levels of HCV replication, enhanced hepatocyte apoptosis and the
      subsequent development of rapidly progressive liver fibrosis. Although the
      responsible mechanisms remain unclear, it is likely that immunosuppressive drugs
      play an important role. It is well known that immunosuppressants impair immune
      control of HCV, thereby allowing increased viral replication. However there is
      also evidence that immunosuppressants may directly induce apoptosis and this may
      be facilitated by the presence of high levels of HCV replication. Thus HCV and
      immunosuppressants may synergistically interact to further enhance apoptosis and
      drive more rapid fibrosis. These findings suggest that modulation of apoptosis
      within the liver either by changing immunosuppressive therapy or the use of
      apoptosis inhibitors may help prevent fibrosis progression in patients with post
      transplant HCV disease.

PMID- 22611310
TI  - Side-stream smoking reduces intestinal inflammation and increases expression of
      tight junction proteins.
AB  - AIM: To investigate the effect of side-stream smoking on gut microflora
      composition, intestinal inflammation and expression of tight junction proteins.
      METHODS: C57BL/6 mice were exposed to side-stream cigarette smoking for one hour
      daily over eight weeks. Cecal contents were collected for microbial composition
      analysis. Large intestine was collected for immunoblotting and quantitative
      reverse transcriptase polymerase chain reaction analyses of the inflammatory
      pathway and tight junction proteins. RESULTS: Side-stream smoking induced
      significant changes in the gut microbiota with increased mouse intestinal
      bacteria, Clostridium but decreased Fermicutes (Lactoccoci and Ruminococcus),
      Enterobacteriaceae family and Segmented filamentous baceteria compared to the
      control mice. Meanwhile, side-stream smoking inhibited the nuclear factor-kappaB
      pathway with reduced phosphorylation of p65 and IkappaBalpha, accompanied with
      unchanged mRNA expression of tumor necrosis factor-alpha or interleukin-6. The
      contents of tight junction proteins, claudin3 and ZO2 were up-regulated in the
      large intestine of mice exposed side-stream smoking. In addition, side-stream
      smoking increased c-Jun N-terminal kinase and p38 MAPK kinase signaling, while
      inhibiting AMP-activated protein kinase in the large intestine. CONCLUSION: Side
      stream smoking altered gut microflora composition and reduced the inflammatory
      response, which was associated with increased expression of tight junction
      proteins.

PMID- 22611311
TI  - Agmatine induces gastric protection against ischemic injury by reducing vascular
      permeability in rats.
AB  - AIM: To investigate the effect of administration of agmatine (AGM) on gastric
      protection against ischemia reperfusion (I/R) injury. METHODS: Three groups of
      rats (6/group); sham, gastric I/R injury, and gastric I/R + AGM (100 mg/kg, i.p.
      given 15 min prior to gastric ischemia) were recruited. Gastric injury was
      conducted by ligating celiac artery for 30 min and reperfusion for another 30
      min. Gastric tissues were histologically studied and immunostained with
      angiopoietin 1 (Ang-1) and Ang-2. Vascular endothelial growth factor (VEGF) and
      monocyte chemoattractant protein-1 (MCP-1) were measured in gastric tissue
      homogenate. To assess whether AKt/phosphatidyl inositol-3-kinase (PI3K) mediated
      the effect of AGM, an additional group was pretreated with Wortmannin (WM)
      (inhibitor of Akt/PI3K, 15 MUg/kg, i.p.), prior to ischemic injury and AGM
      treatment, and examined histologically and immunostained. Another set of
      experiments was run to study vascular permeability of the stomach using Evan's
      blue dye. RESULTS: AGM markedly reduced Evan's blue dye extravasation (3.58 +/-
      0.975 MUg/stomach vs 1.175 +/- 0.374 MUg/stomach, P < 0.05), VEGF (36.87 +/- 2.71
      pg/100 mg protein vs 48.4 +/- 6.53 pg/100 mg protein, P < 0.05) and MCP-1 tissue
      level (29.5 +/- 7 pg/100 mg protein vs 41.17 +/- 10.4 pg/100 mg protein, P <
      0.01). It preserved gastric histology and reduced congestion. Ang-1 and Ang-2
      immunostaining were reduced in stomach sections of AGM-treated animals. The
      administration of WM abolished the protective effects of AGM and extensive
      hemorrhage and ulcerations were seen. CONCLUSION: AGM protects the stomach
      against I/R injury by reducing vascular permeability and inflammation. This
      protection is possibly mediated by Akt/PI3K.

PMID- 22611312
TI  - Protective effects of 5-methoxypsoralen against acetaminophen-induced
      hepatotoxicity in mice.
AB  - AIM: To investigate the hepatic protective effects of 5-methoxypsoralen (5-MOP)
      and to learn if 5-MOP causes hepatotoxicity at protective doses. METHODS:
      C57BL/6J mice were administrated orally with 5-MOP at doses of 12.5, 25 and 50
      mg/kg body weight respectively every morning for 4 d before given acetaminophen
      (APAP) subcutaneously at a dose of 500 mg/kg. The 5-MOP alone group was treated
      with 5-MOP orally at a dose of 50 mg/kg body weight for 4 d without APAP. Twenty
      four hours after APAP administration, blood samples of mice were analyzed for
      serum enzyme alanine transaminase (ALT), aspartate transaminase (AST), lactate
      dehydrogenase (LDH) levels, and malondialdehyde (MDA), reduced glutathione (GSH)
      and oxidized glutathione (GSSG) of liver tissues were measured and
      histopathologic changes of the liver were observed. RESULTS: Compared with the
      vehicle control group, the serum levels (IU/L) of ALT, AST and LDH were all
      increased significantly in APAP group (8355 +/- 3940 vs 30 +/- 21, P < 0.05; 6482
      +/- 4018 vs 146 +/- 58, P < 0.05; 24627 +/- 10975 vs 1504 +/- 410, P < 0.05).
      Compared with APAP group, the serum ALT levels (IU/L) (1674 +/- 1810 vs 8355 +/-
      3940, P < 0.05; 54 +/- 39 vs 8355 +/- 3940, P < 0.05; 19 +/- 9 vs 8355 +/- 3940,
      P < 0.05), AST levels (IU/L) (729 +/- 685 vs 6482 +/- 4108, P < 0.05; 187 +/- 149
      vs 6482 +/- 4108, P < 0.05; 141 +/- 12 vs 6482 +/- 4108, P < 0.05) and LDH levels
      (IU/L) (7220 +/- 6317 vs 24 627 +/- 10 975, P < 0.05; 1618 +/- 719 vs 24 627 +/-
      10 975, P < 0.05; 1394 +/- 469 vs 24 627 +/- 10 975, P < 0.05) were all decreased
      drastically in the three-dosage 5-MOP pretreatment groups. Pretreatment of 5-MOP
      could attenuate histopathologic changes induced by APAP, including hepatocellular
      necrosis and infiltration of inflammatory cells, and the effect was dose
      dependent. MDA levels (nmol/mg) were decreased by 5-MOP in a dose-dependent
      manner (0.98 +/- 0.45 vs 2.15 +/- 1.07, P > 0.05; 0.59 +/- 0.07 vs 2.15 +/- 1.07,
      P < 0.05; 0.47 +/- 0.06 vs 2.15 +/- 1.07, P < 0.05). The pretreatment of 5-MOP
      could also increase the GSH/GSSG ratio (3.834 +/- 0.340 vs 3.306 +/- 0.282, P >
      0.05; 5.330 +/- 0.421 vs 3.306 +/- 0.282, P < 0.05; 6.180 +/- 0.212 vs 3.306 +/-
      0.282, P < 0.05). In the group treated with 5-MOP but without APAP, the serum
      enzyme levels, the liver histopathologic manifestation, and the values of MDA and
      GSH/GSSG ratio were all normal. CONCLUSION: 5-MOP can effectively protect
      C57BL/6J mice from APAP-induced hepatotoxicity and possesses an antioxidative
      activity, and does not cause liver injury at the protective doses.

PMID- 22611314
TI  - Satisfaction with patient-doctor relationships in inflammatory bowel diseases:
      examining patient-initiated change of specialist.
AB  - AIM: To assess the reasons for, and factors associated with, patient-initiated
      changes in treating specialist in inflammatory bowel diseases (IBD). METHODS:
      Prospectively identified IBD patients (n = 256) with >= 1 encounter at a
      metropolitan hospital were surveyed, including whether they had changed treating
      specialist and why. Negative reasons included loss of confidence, disagreement,
      and/or personality clash with the specialist. RESULTS: Of 162 respondents, 70
      (43%) had ever changed specialists; 30/70 (43%) for negative reasons, 52/70 (74%)
      in the preceding year. Patients with negative reasons for changing (n = 30) were
      younger (median, 35.2 years vs 45.3 years), had higher IBD knowledge (median, 5.0
      years vs 4.0 years), yet had lower medication adherence and satisfaction scores
      (median, 19.0 years vs 22.0 years, 14.0 years vs 16.0 years respectively, Mann
      Whitney tests, all P < 0.05), compared to all other responders (n = 132).
      Patients with a recent change (for any reason) were more likely to have Crohn's
      disease, currently active disease, previous bowel resection and recent
      hospitalization [OR 2.6, 95% CI (1.3-5.4), 2.2 (1.0-4.7), 5.56 (1.92-16.67), 2.0
      (1.3-3.0), each P < 0.05]. CONCLUSION: Changing specialist appears associated
      with patient- related (age, nonadherence) and contemporaneous disease-related
      factors (recent relapse) which, where modifiable, may enhance patient-doctor
      relationships and therefore quality of care.

PMID- 22611313
TI  - Effect of soy protein supplementation in patients with chronic hepatitis C: a
      randomized clinical trial.
AB  - AIM: To evaluate the effects of soy supplementation on insulin resistance, fatty
      liver and alanine aminotransferase (ALT) levels in non-diabetic patients with
      chronic hepatitis C (CHC). METHODS: In a prospective, randomized and single
      blinded clinical trial, we compared patients with CHC who had casein as a
      supplement (n = 80) (control group), with patients who consumed a soy supplement
      diet (n = 80) [intervention group (IG)]. Both groups received 32 g/d of protein
      for 12 wk. RESULTS: Patients' baseline features showed that 48.1% were
      overweight, 43.7% had abdominal fat accumulation, 34.7% had hepatic steatosis and
      36.3% had an homeostasis model assessment index of insulin resistance (HOMA-IR)
      >= 3.0. Descriptive analysis showed that protein supplementation diet reduced
      hepatic steatosis in both groups; however, significant reductions in ALT levels
      occurred in the soy group. Multiple regression modeling indicated that in the
      presence of severe fibrosis (F3/F4), gamma glutamyl transferase elevation and
      high density lipoprotein (HDL) reduction, the intervention group had 75% less
      chance of developing hepatic steatosis (OR= 0.25; 95% CI: 0.06-0.82) and 55% less
      chance of presenting with an ALT level >= 1.5 * the upper limit of normal (ULN)
      (OR = 0.45, 95% CI: 0.22-0.89). Soy treatment did not have any effect on insulin
      resistance (OR = 1.92; 95% CI: 0.80-4.83), which might be attributed to the fact
      that the HOMA-IR values at baseline in most of our patients were in the normal
      range. Advanced hepatic fibrosis, an ALT level > 1.5 * ULN and visceral fat were
      predictors of an HOMA-IR >= 3. The IG group had a reduced risk of an ALT level >
      1.5 * ULN. An HOMA-IR >= 3.0 and HDL < 35 mg/dL were also risk factors for
      increased ALT. CONCLUSION: Soy supplementation decreased ALT levels and thus may
      improve liver inflammation in hepatitis C virus (HCV) patients; it also reduced
      hepatic steatosis in a subgroup of patients but did not change insulin
      resistance. It should be considered in the nutritional care of HCV patients.

PMID- 22611315
TI  - Endoclips vs large or small-volume epinephrine in peptic ulcer recurrent
      bleeding.
AB  - AIM: To compare the recurrent bleeding after endoscopic injection of different
      epinephrine volumes with hemoclips in patients with bleeding peptic ulcer.
      METHODS: Between January 2005 and December 2009, 150 patients with gastric or
      duodenal bleeding ulcer with major stigmata of hemorrhage and nonbleeding visible
      vessel in an ulcer bed (Forrest IIa) were included in the study. Patients were
      randomized to receive a small-volume epinephrine group (15 to 25 mL injection
      group; Group 1, n = 50), a large-volume epinephrine group (30 to 40 mL injection
      group; Group 2, n = 50) and a hemoclip group (Group 3, n = 50). The rate of
      recurrent bleeding, as the primary outcome, was compared between the groups of
      patients included in the study. Secondary outcomes compared between the groups
      were primary hemostasis rate, permanent hemostasis, need for emergency surgery,
      30 d mortality, bleeding-related deaths, length of hospital stay and transfusion
      requirements. RESULTS: Initial hemostasis was obtained in all patients. The rate
      of early recurrent bleeding was 30% (15/50) in the small-volume epinephrine group
      (Group 1) and 16% (8/50) in the large-volume epinephrine group (Group 2) (P =
      0.09). The rate of recurrent bleeding was 4% (2/50) in the hemoclip group (Group
      3); the difference was statistically significant with regard to patients treated
      with either small-volume or large-volume epinephrine solution (P = 0.0005 and P =
      0.045, respectively). Duration of hospital stay was significantly shorter among
      patients treated with hemoclips than among patients treated with epinephrine
      whereas there were no differences in transfusion requirement or even 30 d
      mortality between the groups. CONCLUSION: Endoclip is superior to both small and
      large volume injection of epinephrine in the prevention of recurrent bleeding in
      patients with peptic ulcer.

PMID- 22611316
TI  - Beneficial effects of fucoidan in patients with chronic hepatitis C virus
      infection.
AB  - AIM: To evaluate the effects of fucoidan, a complex sulfated polysaccharide
      extract from marine seaweed, on hepatitis C virus (HCV) RNA load both in vitro
      and in vivo. METHODS: HCV-1b replicon-expressing cells were cultured in the
      presence of fucoidan obtained from Cladosiphon okamuranus Tokida cultivated in
      Okinawa, Japan, and quantified the level of HCV replication. In an open-label
      uncontrolled study, 15 patients with chronic hepatitis C, and HCV-related
      cirrhosis and hepatocellular carcinoma were treated with fucoidan (0.83 g/d) for
      12 mo. The clinical symptoms, biochemical tests, and HCV RNA levels were assessed
      before, during, and after treatment. RESULTS: Fucoidan dose-dependently inhibited
      the expression of HCV replicon. At 8-10 mo of treatment with fucoidan, HCV RNA
      levels were significantly lower relative to the baseline. The same treatment also
      tended to lower serum alanine aminotransferase levels, and the latter correlated
      with HCV RNA levels. However, the improved laboratory tests did not translate
      into significant clinical improvement. Fucoidan had no serious adverse effects.
      CONCLUSION: Our findings suggest that fucoidan is safe and useful in the
      treatment of patients with HCV-related chronic liver diseases. Further controlled
      clinical trials are needed to confirm the present findings.

PMID- 22611317
TI  - Plasma levels of acylated ghrelin in patients with functional dyspepsia.
AB  - AIM: To investigate the relationship between plasma acylated ghrelin levels and
      the pathophysiology of functional dyspepsia. METHODS: Twenty-two female patients
      with functional dyspepsia and twelve healthy volunteers were recruited for the
      study. The functional dyspepsia patients were each diagnosed based on the Rome
      III criteria. Eligible patients completed a questionnaire concerning the severity
      of 10 symptoms. Plasma acylated ghrelin levels before and after a meal were
      determined in the study participants using a commercial human acylated enzyme
      immunoassay kit; electrogastrograms were performed for 50 min before and after a
      standardized 10-min meal containing 265 kcal. RESULTS: There were no significant
      differences in plasma acylated ghrelin levels between healthy volunteers and
      patients with functional dyspepsia. However, in patients with functional
      dyspepsia, there was a negative correlation between fasting plasma acylated
      ghrelin levels and the sum score of epigastric pain (r = -0.427, P = 0.047) and a
      positive correlation between the postprandial/fasting plasma acylated ghrelin
      ratio and the sum score of early satiety (r = 0.428, P =0.047). Additionally,
      there was a negative correlation between fasting acylated ghrelin plasma levels
      and fasting normogastria (%) (r = -0.522, P = 0.013). Interestingly, two
      functional dyspepsia patients showed paradoxically elevated plasma acylated
      ghrelin levels after the meal. CONCLUSION: Abnormal plasma acylated ghrelin
      levels before or after a meal may be related to several of the dyspeptic symptoms
      seen in patients with functional dyspepsia.

PMID- 22611318
TI  - Knowledge levels and attitudes of health care professionals toward patients with
      hepatitis C infection.
AB  - AIM: To study knowledge levels and attitudes of health care providers toward
      patients with hepatitis C virus infection in Guilan, a northern province of Iran.
      METHODS: This cross-sectional study was performed on 239 health care
      professionals from the Razi Hospital, including doctors, nurses, and operating
      room technicians. The questionnaires consisted of questions on demographic
      characteristics, knowledge levels, and attitudes toward hepatitis C patients. The
      questionnaire was tested in a pilot study and validated by Cronbach's alpha
      coefficient. Data were analyzed using SPSS16 software. RESULTS: The mean +/- SD
      knowledge score was 17.43 +/- 2.65 (from a total of 22). 51.9% of the
      participants achieved scores higher than the mean. There was a significant
      relationship between knowledge score and age (P = 0.001), gender (P = 0.0001),
      occupational history (P = 0.0001), and educational history (P = 0.027). There was
      also a significant relationship between attitude level and age (P = 0.002),
      gender (P = 0.0001), occupational history (P = 0.0001), and educational history
      (P = 0.035). Physicians were significantly more knowledgeable and showed more
      positive attitudes. There was a positive correlation between knowledge and
      attitude scores (P = 0.02). CONCLUSION: Discriminatory attitudes are common among
      health care providers toward hepatitis C patients. It is therefore necessary to
      improve their knowledge level and attitude toward this disease.

PMID- 22611319
TI  - Antibiotic resistance and cagA gene correlation: a looming crisis of Helicobacter
      pylori.
AB  - AIM: To determine antibiotic resistance of Helicobacter pylori (H. pylori) in
      Pakistan and its correlation with host and pathogen associated factors. METHODS:
      A total of 178 strains of H. pylori were isolated from gastric biopsies of
      dyspeptic patients. Susceptibility patterns against first and second-line
      antibiotics were determined and trends of resistance were analyzed in relation to
      the sampling period, gastric conditions and cagA gene carriage. The effect of
      cagA gene on the acquisition of resistance was investigated by mutant selection
      assay. RESULTS: The observations showed that monoresistant strains were prevalent
      with rates of 89% for metronidazole, 36% for clarithromycin, 37% for amoxicillin,
      18.5% for ofloxacin and 12% for tetracycline. Furthermore, clarithromycin
      resistance was on the rise from 2005 to 2008 (32% vs 38%, P = 0.004) and it is
      significantly observed in non ulcerative dyspeptic patients compared to
      gastritis, gastric ulcer and duodenal ulcer cases (53% vs 20%, 18% and 19%, P =
      0.000). On the contrary, metronidazole and ofloxacin resistance were more common
      in gastritis and gastric ulcer cases. Distribution analysis and frequencies of
      resistant mutants in vitro correlated with the absence of cagA gene with
      metronidazole and ofloxacin resistance. CONCLUSION: The study confirms the
      alarming levels of antibiotic resistance associated with the degree of gastric
      inflammation and cagA gene carriage in H. pylori strains.

PMID- 22611320
TI  - CD74 and macrophage migration inhibitory factor as therapeutic targets in gastric
      cancer.
AB  - AIM: To investigate the relationship and molecular features of CD74/macrophage
      migration inhibitory factor (MIF)/Toll-like receptor 4 (TLR4) in gastric cancer.
      METHODS: CD74, MIF and TLR4 expression in the paraffin-embedded sections of
      gastric cancer from 120 patients were detected by immunohistochemical staining.
      Knock down of CD74 expression in gastric cancer cell line MKN-45 was performed by
      lentivirus transduction and detected by Western blotting. MKN-45 cell
      proliferation assay under the stimulants was measured by the cell counting kit 8
      (CCK8) assay and MIF concentration in the culture medium was detected by enzyme
      linked immunosorbent assay. Surface staining of CD74 in the MKN-45 cell line
      under the stimulation of lipopolysaccharide (LPS) was measured by flow cytometry.
      MIF, CD74 and TLR4 co-localization in the MKN-45 cell line was performed by the
      immunoprecipitation. RESULTS: CD74, MIF and TLR4 were found to be expressed in
      gastric cancer and increased significantly in the advanced stage, and were also
      associated with lymph node metastasis. Correlation analysis revealed that CD74
      was positively correlated with MIF (r = 0.2367, P < 0.01) and both proteins were
      also associated with TLR4 (r = 0.4414, r = 0.5001, respectively, P < 0.01). LPS
      can significantly promote MKN-45 cell proliferation (3.027 +/- 0.388 vs 4.201 +/-
      0.092, P < 0.05), induce MIF production (54.333 +/- 2.906 pg/mL vs 29.667 +/-
      3.180 pg/mL, P < 0.01) and cell surface expression of CD74 (75.6% +/- 4.046% vs
      9.4% +/- 0.964%, P < 0.01) at LPS concentration of 1 MUg/mL compared to medium
      control. Knockdown of CD74 or using anti-CD74 and MIF antagonist ISO-1
      significantly reduced LPS-induced MKN-45 cell proliferation (4.201 +/- 0.092 vs
      3.337 +/- 0.087, 4.534 +/- 0.222 vs 3.368 +/- 0.290, 4.058 +/- 0.292 vs 2.934 +/-
      0.197, respectively, P < 0.01). MIF, CD74 and TLR4 could co-localize in the MKN
      45 cell line. CONCLUSION: Upregulation of MIF, CD74 and TLR4 are associated with
      increasing clinical stage and provide an opportunity as novel gastric cancer
      chemoprevention and/or treatment strategy.

PMID- 22611321
TI  - Preventive effects of geranylgeranylacetone on rat ethanol-induced gastritis.
AB  - AIM: To establish a rat ethanol gastritis model, we evaluated the effects of
      ethanol on gastric mucosa and studied the preventive effects of
      geranylgeranylacetone on ethanol-induced chronic gastritis. METHODS: One hundred
      male Sprague-Dawley rats were randomly divided into 4 equal groups: normal
      control group, undergoing gastric perfusion of normal saline (NS) by
      gastrogavage; model control group and 2 model therapy groups that underwent
      gastric perfusion with ethanol (distillate spirits with 56% ethanol content) by
      gastrogavage for 4 wk. Low or high doses of geranylgeranylacetone were added 1 h
      before ethanol perfusion in the 2 model therapy groups, while the same amount of
      NS, instead of geranylgeranylacetone was used in that model control group. The
      rats were then sacrificed and stomachs were removed. The injury level of the
      gastric mucosa was observed by light and electron microscopy, and the levels of
      prostaglandin 2 (PGE2), endothelin-1 (ET-1) and nitric oxide (NO) were measured
      by radioimmunoassay and the Griess method. RESULTS: The gastric mucosal epidermal
      damage score (EDS; 4.5) and ulcer index (UI; 12.0) of the model control group
      were significantly higher than that of the normal control group (0 and 0
      respectively, all P = 0.000). The gastric mucosal EDS and UI of the 2 model
      therapy groups (EDS: 2.5 and 2.0; UI: 3.5 and 3.0) were significantly lower than
      that of the model control group (all P < 0.01). There was no statistically
      significant difference between the low-dose and high-dose model therapy groups.
      The expression value of plasma ET-1 of the model control group was higher than
      that of the normal control group (P < 0.01) and the 2 model therapy groups (all P
      < 0.01). The expression values of gastric mucosal PGE2 and serum NO of the model
      control group were lower than those of the normal control group (all P < 0.05)
      and the 2 model therapy groups (all P < 0.05). The thickness of the gastric
      mucous layerand the hexosamine content in the model control group were
      significantly lower than that in the normal control group (all P < 0.01) and the
      2 model therapy groups (all P < 0.05). Scanning and transmission electron
      microscopy observation showed that in the model control group, the epithelial
      junctions were vague, the intercellular joints disappeared and damage of the
      intracellular organelles were significantly worse than those in the normal
      control group. However, in the 2 model therapy groups, damage to the
      intercellular joints and organelles was ameliorate relative to the model control
      group. CONCLUSION: Administration of geranylgeranylacetone was correlated with a
      more favorable pattern of gastric mucosa damage after ethanol perfusion. The
      mechanism could be related to regulation of ET-1, NO and PGE2.

PMID- 22611322
TI  - Role of bone marrow-derived mesenchymal stem cells in a rat model of severe acute
      pancreatitis.
AB  - AIM: To investigate the role and potential mechanisms of bone marrow mesenchymal
      stem cells (MSCs) in severe acute peritonitis (SAP). METHODS: Pancreatic acinar
      cells from Sprague Dawley rats were randomly divided into three groups: non
      sodium deoxycholate (SDOC) group (non-SODC group), SDOC group, and a MSCs
      intervention group (i.e., a co-culture system of MSCs and pancreatic acinar cells
      + SDOC). The cell survival rate, the concentration of malonaldehyde (MDA), the
      density of superoxide dismutase (SOD), serum amylase (AMS) secretion rate and
      lactate dehydrogenase (LDH) leakage rate were detected at various time points. In
      a separate study, Sprague Dawley rats were randomly divided into either an SAP
      group or an SAP + MSCs group. Serum AMS, MDA and SOD, interleukin (IL)-6, IL-10,
      and tumor necrosis factor (TNF)-alpha levels, intestinal mucosa injury scores and
      proliferating cells of small intestinal mucosa were measured at various time
      points after injecting either MSCs or saline into rats. In both studies, the
      protective effect of MSCs was evaluated. RESULTS: In vitro, The cell survival
      rate of pancreatic acinar cells and the density of SOD were significantly
      reduced, and the concentration of MDA, AMS secretion rate and LDH leakage rate
      were significantly increased in the SDOC group compared with the MSCs
      intervention group and the Non-SDOC group at each time point. In vivo, Serum AMS,
      IL-6, TNF-alpha and MAD level in the SAP + MSCs group were lower than the SAP
      group; however serum IL-10 level was higher than the SAP group. Serum SOD level
      was higher than the SAP group at each time point, whereas a significant between
      group difference in SOD level was only noted after 24 h. Intestinal mucosa injury
      scores was significantly reduced and the proliferating cells of small intestinal
      mucosa became obvious after injecting MSCs. CONCLUSION: MSCs can effectively
      relieve injury to pancreatic acinar cells and small intestinal epithelium,
      promote the proliferation of enteric epithelium and repair of the mucosa,
      attenuate systemic inflammation in rats with SAP.

PMID- 22611323
TI  - Clinical significance of connective tissue growth factor in hepatitis B virus
      induced hepatic fibrosis.
AB  - AIM: To determine the utility of connective tissue growth factor (CCN2/CTGF) for
      assessing hepatic fibrosis in hepatitis B virus (HBV)-induced chronic liver
      diseases (CLD-B). METHODS: Enzyme-linked immunosorbent assay was used to measure
      CCN2 in sera from 107 patients with chronic hepatitis B (CHB) and 39 patients
      with HBV-induced active liver cirrhosis and 30 healthy individuals. Liver samples
      from 31 patients with CHB, 8 patients with HBV-induced liver cirrhosis and 8 HBV
      carriers with normal liver histology were examined for transforming growth factor
      beta-1 (TGF-beta1) or CCN2 mRNA levels by in situ hybridization, and computer
      image analysis was performed to measure integrated optimal density (IOD) of CCN2
      mRNA-positive cells in liver tissues. Histological inflammation grading and
      fibrosis staging were evaluated by H and E staining and Van Gieson's method.
      RESULTS: Serum CCN2 concentrations were, respectively, 4.0- or 4.9-fold higher in
      patients with CHB or active liver cirrhosis as compared to healthy individuals (P
      < 0.01). There was good consistency between the levels of CCN2 in sera and CCN2
      mRNA expression in liver tissues (r = 0.87, P < 0.01). The levels of CCN2 in sera
      were increased with the enhancement of histological fibrosis staging in patients
      with CLD-B (r = 0.85, P < 0.01). Serum CCN2 was a reliable marker for the
      assessment of liver fibrosis, with areas under the receiver operating
      characteristic (ROC) curves (AUC) of 0.94 or 0.85 for, respectively,
      distinguishing normal liver controls from patients with F1 stage liver fibrosis
      or discriminating between mild and significant fibrosis. CONCLUSION: Detection of
      serum CCN2 in patients with CLD-B may have clinical significance for assessment
      of severity of hepatic fibrosis.

PMID- 22611324
TI  - Mycophenolate mofetil for maintenance of remission in steroid-dependent
      autoimmune pancreatitis.
AB  - Systemic corticosteroids represent the standard treatment for autoimmune
      pancreatitis with IgG4-associated cholangitis. For steroid-dependent disease,
      azathioprine has been used for maintenance of remission. Mycophenolate mofetil
      has been used for transplant immunosuppression and more recently for autoimmune
      hepatitis; however, there are no case reports to date on the use of mycophenolate
      mofetil in adult patients with autoimmune pancreatitis. A patient with IgG4
      mediated autoimmune pancreatitis and IgG4-associated cholangitis refractory to
      steroids and intolerant of azathioprine was treated with mycophenolate mofetil,
      which inhibits de novo guanosine synthesis and blockade of both B and T
      lymphocyte production. Introduction of mycophenolate mofetil and uptitration to
      1000 mg by mouth twice daily over a treatment period of 4 mo was associated with
      improvement in the patient's energy level and blood glucose control and was not
      associated with any adverse events. The patient was managed without a biliary
      stent. However, there was a return of symptoms, jaundice, increase in
      transaminases, and hyperbilirubinemia when the prednisone dose reached 11 mg per
      day. In the first report of mycophenolate mofetil use in an adult patient with
      IgG4-associated autoimmune pancreatitis and IgG4-associated cholangitis, the
      introduction of mycophenolate mofetil was safe and well-tolerated without adverse
      events, but it did not enable discontinuation of the steroids. Mycophenolate
      mofetil and other immunomodulatory therapies should continue to be studied for
      maintenance of remission in the large subset of patients with refractory or
      recurrent autoimmune pancreatitis.

PMID- 22611325
TI  - Hepatic artery pseudoaneurysm caused by acute idiopathic pancreatitis.
AB  - Hepatic artery pseudoaneurysm (HAP) is a very rare disease but in cases of
      complication, there is a very high mortality. The most common cause of HAP is
      iatrogenic trauma such as liver biopsy, transhepatic biliary drainage,
      cholecystectomy and hepatectomy. HAP may also occur with complications such as
      infections or inflammation associated with septic emboli. HAP has been reported
      rarely in patients with acute pancreatitis. As far as we are aware, there is no
      report of a case caused by acute idiopathic pancreatitis, particularly. We report
      a case of HAP caused by acute idiopathic pancreatitis which developed in a 61
      year-old woman. The woman initially presented with acute pancreatitis due to
      unknown cause. After conservative management, her symptoms seemed to have
      improved. But eight days after admission, abdominal pain abruptly became worse
      again. Abdominal computed tomography (CT) was rechecked and it detected a new HAP
      that was not seen in a previous abdominal CT. Endoscopic retrograde
      cholangiopancreatography (ERCP) was performed because of a suspicion of hemobilia
      as a cause of aggravated abdominal pain. ERCP confirmed hemobilia by observing
      fresh blood clots at the opening of the ampulla and several filling defects in
      the distal common bile duct on cholangiogram. Without any particular treatment
      such as embolization or surgical ligation, HAP thrombosed spontaneously. Three
      months after discharge, abdominal CT demonstrated that HAP in the left lateral
      segment had disappeared.

PMID- 22611326
TI  - Learning Motivation Mediates Gene-by-Socioeconomic Status Interaction on
      Mathematics Achievement in Early Childhood.
AB  - There is accumulating evidence that genetic influences on achievement are more
      pronounced among children living in higher socioeconomic status homes, and that
      these gene-by-environment interactions occur prior to children's entry into
      formal schooling. We hypothesized that one pathway through which socioeconomic
      status promotes genetic influences on early achievement is by facilitating the
      processes by which children select, evoke, and attend to learning experiences
      that are consistent with genetically influenced individual differences in their
      motivation to learn. We examined this hypothesis in a nationally representative
      sample of approximately 650 pairs of four-year old identical and fraternal twins
      who were administered a measure of math achievement, and rated by their parents
      on a broad set of items assessing learning motivation. Results indicated a
      genetic link between learning motivation and math achievement that varied
      positively with family socioeconomic status: Genetic differences in learning
      motivation contributed to math achievement more strongly in more advantaged
      homes. Once this effect of learning motivation was controlled for, gene-by
      socioeconomic status interaction on math achievement was reduced from previously
      significant levels, to nonsignificant levels.

PMID- 22611327
TI  - Securing the Downside Up: Client and Care Factors Associated with Outcomes of
      Secure Residential Youth Care.
AB  - BACKGROUND: Although secure residential care has the potential of reducing young
      people's behavioral problems, it is often difficult to achieve positive outcomes.
      Research suggests that there are several common success factors of treatment, of
      which the client's motivation for treatment and the quality of the therapeutic
      relationship between clients and therapists might be especially relevant and
      important in the context of secure residential care.  OBJECTIVE: The objective of
      the present study was to explore the association of these potential success
      factors with secure residential care outcomes.  METHODS: A repeated measures
      research design was applied in the study, including a group of adolescents in a
      secure residential care center that was followed up on three measurements in
      time. Interviews and questionnaires concerning care outcomes in terms of
      adolescents' behavior change during care were administered to 22 adolescents and
      27 group care workers. Outcomes in terms of adolescents' treatment satisfaction
      were assessed by the use of questionnaires, which were completed by 51
      adolescents.  RESULTS: Adolescents reported some positive changes in their
      treatment motivation, but those who were more likely to be motivated at admission
      were also more likely to deteriorate in treatment motivation from admission to
      departure. Treatment satisfaction was associated with better treatment motivation
      at admission and with a positive adolescent-group care worker relationship. 
      CONCLUSIONS: The results suggest that outcomes can be improved by a more explicit
      treatment focus on improving the adolescent's treatment motivation and the
      quality of the adolescent-care worker relationship during secure residential
      care.

PMID- 22611328
TI  - The Influence of Education and Socialization on Radicalization: An Exploration of
      Theoretical Presumptions and Empirical Research.
AB  - BACKGROUND AND OBJECTIVE: Research into radicalization does not pay much
      attention to education. This is remarkable and possibly misses an important
      influence on the process of radicalization. Therefore this article sets out to
      explore the relation between education on the one hand and the onset or
      prevention of radicalization on the other hand.  METHOD: This article is a
      theoretical literature review. It has analyzed empirical studies-mainly from
      European countries-about the educational aims, content and style of Muslim
      parents and parents with (extreme) right-wing sympathies.  RESULTS: Research
      examining similarity in right-wing sympathies between parents and children yields
      mixed results, but studies among adolescents point to a significant concordance.
      Research also showed that authoritarian parenting may play a significant role.
      Similar research among Muslim families was not found. While raising children with
      distrust and an authoritarian style are prevalent, the impact on adolescents has
      not been investigated. The empirical literature we reviewed does not give
      sufficient evidence to conclude that democratic ideal in and an authoritative
      style of education are conducive to the development of a democratic attitude. 
      CONCLUSION: There is a knowledge gap with regard to the influence of education on
      the onset or the prevention of radicalization. Schools and families are
      underappreciated sources of informal social control and social capital and
      therefore the gap should be closed. If there is a better understanding of the
      effect of education, policy as well as interventions can be developed to assist
      parents and teachers in preventing radicalization.

PMID- 22611329
TI  - The effect of seating preferences of the medical students on educational
      achievement.
AB  - BACKGROUND: The seat selection and classroom dynamics may have mutual influence
      on the student performance and participation in both assigned and random seating
      arrangement. PURPOSE: The aim of the study was to understand the influence of
      seat selection on educational achievement. METHODS: The seating positions of the
      medical students were recorded on an architectural plan during each class session
      and the means and standard deviations of the students' locations were calculated
      in X and Y orientations. The locations of the students in the class were analyzed
      based on three architectural classifications: interactional zone, distance from
      the board, and access to the aisles. Final exam scores were used to measure the
      students' educational achievement. RESULTS: Our results demonstrate that there is
      a statistically significant relationship between the student's locations in the
      class and their attendance and educational achievements. CONCLUSION: two factors
      may effect on educational achievement: student seating in the high interactional
      zone and minimal changes in seating location. Seating in the high interaction
      zone was directly associated with higher performance and inversely correlated
      with the percentage of absences. This observation is consistent with the view
      that students in the front of the classroom are likely more motivated and
      interact with the lecturer more than their classmates.

PMID- 22611330
TI  - An innovative quality improvement curriculum for third-year medical students.
AB  - BACKGROUND: Competence in quality improvement (QI) is a priority for medical
      students. We describe a self-directed QI skills curriculum for medical students
      in a 1-year longitudinal integrated third-year clerkship: an ideal context to
      learn and practice QI. METHODS: Two groups of four students identified a quality
      gap, described existing efforts to address the gap, made quantifying measures,
      and proposed a QI intervention. The program was assessed with knowledge and
      attitude surveys and a validated tool for rating trainee QI proposals. Reaction
      to the curriculum was assessed by survey and focus group. RESULTS: Knowledge of
      QI concepts did not improve (mean knowledge score+/-SD): pre: 5.9+/-1.5 vs. post:
      6.6+/-1.3, p=0.20. There were significant improvements in attitudes (mean topic
      attitude score+/-SD) toward the value of QI (pre: 9.9+/-1.8 vs. post: 12.6+/-1.9,
      p=0.03) and confidence in QI skills (pre: 13.4+/-2.8 vs. post: 16.1+/-3.0,
      p=0.05). Proposals lacked sufficient analysis of interventions and evaluation
      plans. Reaction was mixed, including appreciation for the experience and
      frustration with finding appropriate mentorship. CONCLUSION: Clinical-year
      students were able to conduct a self-directed QI project. Lack of improvement in
      QI knowledge suggests that self-directed learning in this domain may be
      insufficient without targeted didactics. Higher order skills such as developing
      measurement plans would benefit from explicit instruction and mentorship. Lessons
      from this experience will allow educators to better target QI curricula to
      medical students in the clinical years.

PMID- 22611331
TI  - Detection of Propensity for Aggression based on Facial Structure Irrespective of
      Face Race.
AB  - The human face provides a wealth of information pertaining to the internal state
      and life-stage history of an individual. Facial width-to-height ratio is a size
      independent sexually dimorphic trait, and estimates of aggression made by
      untrained adults judging own-race faces were positively associated with both
      facial width-to-height ratio and actual aggressive behavior. Given the
      significant adaptive value of accurately detecting aggressiveness based on facial
      appearance, we hypothesized that aggression estimates made by adults and 8-year
      olds would be highly correlated with male facial width-to-height ratio even for a
      face category with which they had minimal experience-other-race faces. For each
      of the four race and age groups, estimates of aggression were positively
      correlated with facial width-to-height ratio irrespective of rating own-or other
      race faces. Overall, the correlations between facial width-to-height ratio and
      ratings of aggression were stronger for adults than for children. Sensitivity to
      facial width-to-height ratio appears to be part of an evolved mechanism designed
      to detect threats in the external environment. This mechanism is likely broadly
      tuned and functions independently of experience.

PMID- 22611332
TI  - Review of the Eustrophinae (Coleoptera, Tetratomidae) of America north of Mexico.
AB  - The Nearctic fauna (north of Mexico) of Eustrophinae is reviewed, and consists of
      the following five genera and 12 species: Pseudoholostrophus (Pseudoholostrophus)
      impressicollis (LeConte), Pseudoholostrophus (Holostrophinus) discolor (Horn),
      Holostrophus bifasciatus (Say), Eustrophus tomentosus Say, Eustrophopsis confinis
      (LeConte), Eustrophopsis bicolor (Fabricius), Eustrophopsis brunneimarginatus
      (Dury), Eustrophopsis indistinctus (LeConte), Eustrophopsis arizonensis (Horn),
      Eustrophopsis ornatus (Van Dyke), Eustrophopsis crowdyisp. n., and Synstrophus
      repandus (Horn). A lectotype is designated for Eustrophus brunneimarginatus Dury.
      A key is given to separate genera and species, supplemented with illustrations of
      relevant features, including aedeagi of all Nearctic species of Eustrophopsis.
      Detailed distribution (including Mexican records) and natural history data are
      provided.

PMID- 22611333
TI  - Codeswitching in Bilingual Children with Specific Language Impairment.
AB  - Children with specific language impairment (SLI) exhibit limited grammatical
      skills compared to their peers with typical language. These difficulties may be
      revealed when alternating their two languages (i.e., codeswitching) within
      sentences. Fifty-eight Spanish-English speaking children with and without SLI
      produced narratives using wordless picture books and conversational samples. The
      results indicated no significant differences in the proportion of utterances with
      codeswitching (CS) across age groups or contexts of elicitation. There were
      significant effects for language dominance, language of testing, and a
      significant dominance by language of testing interaction. The English-dominant
      children demonstrated more CS when tested in their nondominant language (Spanish)
      compared to the Spanish-dominant children tested in their weaker English. The
      children with SLI did not display more CS or more instances of atypical CS
      patterns compared to their typical peers. The findings indicate that children
      with SLI are capable of using grammatical CS, in spite of their language
      difficulties. In addition, the analyses suggest that CS is sensitive to
      sociolinguistic variables such as when the home language is not socially
      supported in the larger sociocultural context. In these cases, children may
      refrain from switching to the home language, even if that is their dominant
      language.

PMID- 22611334
TI  - Family-Centered Care of the Surgical Neonate.

PMID- 22611336
TI  - The eIF4F and eIFiso4F Complexes of Plants: An Evolutionary Perspective.
AB  - Translation initiation in eukaryotes requires a number of initiation factors to
      recruit the assembled ribosome to mRNA. The eIF4F complex plays a key role in
      initiation and is a common target point for regulation of protein synthesis. Most
      work on the translation machinery of plants to date has focused on flowering
      plants, which have both the eIF4F complex (eIF4E and eIF4G) as well as the plant
      specific eIFiso4F complex (eIFiso4E and eIFiso4G). The increasing availability of
      plant genome sequence data has made it possible to trace the evolutionary history
      of these two complexes in plants, leading to several interesting discoveries.
      eIFiso4G is conserved throughout plants, while eIFiso4E only appears with the
      evolution of flowering plants. The eIF4G N-terminus, which has been difficult to
      annotate, appears to be well conserved throughout the plant lineage and contains
      two motifs of unknown function. Comparison of eIFiso4G and eIF4G sequence data
      suggests conserved features unique to eIFiso4G and eIF4G proteins. These findings
      have answered some questions about the evolutionary history of the two eIF4F
      complexes of plants, while raising new ones.

PMID- 22611335
TI  - The Bic-C family of developmental translational regulators.
AB  - Regulation of mRNA translation is especially important during cellular and
      developmental processes. Many evolutionarily conserved proteins act in the
      context of multiprotein complexes and modulate protein translation both at the
      spatial and the temporal levels. Among these, Bicaudal C constitutes a family of
      RNA binding proteins whose founding member was first identified in Drosophila and
      contains orthologs in vertebrates. We discuss recent advances towards
      understanding the functions of these proteins in the context of the cellular and
      developmental biology of many model organisms and their connection to human
      disease.

PMID- 22611337
TI  - Pseudogenes.
AB  - Pseudogenes are ubiquitous and abundant in genomes. Pseudogenes were once called
      "genomic fossils" and treated as "junk DNA" several years. Nevertheless, it has
      been recognized that some pseudogenes play essential roles in gene regulation of
      their parent genes, and many pseudogenes are transcribed into RNA. Pseudogene
      transcripts may also form small interfering RNA or decrease cellular miRNA
      concentration. Thus, pseudogenes regulate tumor suppressors and oncogenes. Their
      essential functions draw the attention of our research group in my current work
      on heat shock protein 90: a chaperone of oncogenes. The paper reviews our current
      knowledge on pseudogenes and evaluates preliminary results of the chaperone data.
      Current efforts to understand pseudogenes interactions help to understand the
      functions of a genome.

PMID- 22611338
TI  - Modeling Pressure-Driven Transport of Proteins through a Nanochannel.
AB  - Reducing the size of a nanofluidic channel not only creates new opportunities for
      high-precision manipulation of biological macromolecules, but also makes the
      performance of the entire nanofluidic system more susceptible to undesirable
      interactions between the transported biomolecules and the walls of the channel.
      In this manuscript, we report molecular dynamics simulations of a pressure-driven
      flow through a silica nanochannel that characterized, with atomic resolution,
      adsorption of a model protein to its surface. Although the simulated adsorption
      of the proteins was found to be nonspecific, it had a dramatic effect on the rate
      of the protein transport. To determine the relative strength of the protein
      silica interactions in different adsorbed states, we simulated flow-induced
      desorption of the proteins from the silica surface. Our analysis of the protein
      conformations in the adsorbed states did not reveal any simple dependence of the
      adsorption strength on the size and composition of the protein-silica contact,
      suggesting that the heterogeneity of the silica surface may be a important
      factor.

PMID- 22611339
TI  - Impact of environmental thermal stimulation on activation of hypothalamic
      neuronal nitric oxide synthase during the prenatal ontogenesis in Muscovy ducks.
AB  - The aim of the study is to investigate the influence of prenatal temperature
      stimulation on neuronal NO synthase (nNOS) expression in the anterior
      hypothalamus of Muscovy duck embryos. Experiments were performed on embryonic day
      (E) E20, E23, E28, and E33 using histochemistry for identification of the
      nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) as marker of NOS
      containing neurons. Until the experiments, all duck embryos were incubated under
      standard temperature conditions (37.5 degrees C). During 3 hours before the start
      of the experiments, one group was incubated at 37.5 degrees C (control group),
      the second was warm-experienced at 39 degrees C, and the third was cold
      experienced at 34 degrees C. In normal and warm-incubated duck embryos, nNOS
      activity could be first detected on E23. Particularly, after cold stimulation, a
      significant increase in nNOS activity was found in all embryos investigated even
      on day 20. Warm stimulation obviously induces the opposite effect, but at later
      embryonic age (E33). It can be concluded that probably in late-term bird embryos
      NO acts as a mediator of the neuronal cold pathway in the anterior hypothalamus,
      which might be improved by prenatal cold stimulation.

PMID- 22611340
TI  - Quadrature RF Coil for In Vivo Brain MRI of a Macaque Monkey in a Stereotaxic
      Head Frame.
AB  - We present a quadrature volume coil designed for brain imaging of a macaque
      monkey fixed in a sphinx position (facing down the bore) within a stereotactic
      frame at 3 T, where the position of the monkey and presence of the frame preclude
      use of existing coils. Requirements include the ability to position and remove
      the coil without disturbing the position of the monkey in the frame. A saddle
      coil and a solenoid were combined on a modified cylindrical former and connected
      in quadrature as to produce a homogeneous circularly polarized field throughout
      the brain. To allow the loops of the saddle coil to encompass the ear posts,
      partial disassembly and reassembly were facilitated by embedding pin and socket
      contacts into separate pieces of the former. Coil design included simulation of
      the electromagnetic fields for the coil containing a 3D model of a monkey's head.
      The resulting coil produced adequate homogeneity and signal-to-noise ratio
      throughout the brain.

PMID- 22611341
TI  - What is the Best Way to Produce Consensus and Buy in to Guidelines for Rectal
      Cancer?
AB  - Evidence-based guidelines are important tools and common pathways for translating
      evidence into clinical practice. It is most urgently needed when significant
      heterogeneity in practice exist. Actively engaging opinion leaders in the process
      of evidence-based guidelines development is important for several reasons. These
      include allowing the collective views of the practice communities to be
      represented, resolving heterogeneity in practice through discussion, and allowing
      credible recommendations to be formulated. Most importantly, the process itself
      is a tool for facilitating dissemination and implementation. Recognizing the gap
      between practice pattern and guideline recommendations, and devising strategies
      to address it represent an important step toward maximizing concordance between
      guideline and practice. Evidence-based recommendations serve as important
      reference points, against which we can measure, debate, and innovate from.

PMID- 22611342
TI  - The Importance of the Pathologist's Role in Assessment of the Quality of the
      Mesorectum.
AB  - Total mesorectal excision (TME) is considered standard of care for rectal cancer
      treatment. Failure to remove the mesorectal fat envelope entirely may explain
      part of observed local and distant recurrences. Several studies suggest quality
      of the mesorectum after TME surgery as determined by pathological evaluation may
      influence prognosis. We aimed to determine the prognostic value of the plane of
      surgery as well as factors influencing the likelihood of a high-quality specimen
      by reviewing the literature. A pooled meta-analysis of relevant outcome data was
      performed where appropriate. A muscularis propria resection plane was found to
      increase the risk of local recurrence (RR 2.72 [95 % CI 1.36 to 5.44]) and
      overall recurrence (RR 2.00 [95 % CI 1.17 to 3.42]) compared to an
      (intra)mesorectal plane. Plane of surgery is an important factor in rectal cancer
      treatment and the documentation by pathologists is essential for the improvement
      of TME quality and patient outcome.

PMID- 22611344
TI  - Brain-Spleen Inflammatory Coupling: A Literature Review.
AB  - Recent evidence suggests a link between brain injury and the autonomic release of
      pro-inflammatory cytokines by resident macrophages in the spleen. This
      phenomenon, termed "brain-spleen inflammatory coupling," has garnered attention
      from scientific and medical communities interested in developing novel treatments
      for traumatic brain injury (TBI). Cholinergic stimulation of the alpha7-subunit
      nicotinic acetylcholine receptor (alpha7NAchR) on splenic macrophages has been
      shown to inhibit their release of pro-inflammatory cytokines. This inhibition,
      mediated by the parasympathetic nervous system, has been shown to improve
      outcomes in animal models of sepsis, stroke, and TBI. As evidence of a beneficial
      role of splenic inhibition grows, new treatment strategies might be applied to
      many medical conditions involving neuroinflammation, a process that contributes
      to further neurological deterioration.

PMID- 22611343
TI  - Does Radiofrequency Ablation Add to Chemotherapy for Unresectable Liver
      Metastases?
AB  - In patients with unresectable colorectal liver metastases (CRLM), radiofrequency
      ablation (RFA) might be a good alternative, whenever possible. In contrast to
      systemic therapy, the aim of RFA is to achieve complete local tumor control in an
      attempt to provide long-term survival. In this article we discuss the available
      evidence regarding the treatment of patients with unresectable CRLM, focusing on
      RFA in conjunction with modern systemic therapies. We observed that the available
      evidence in the existing literature is limited, and often consists of level 2 and
      3 evidence, thereby hampering any firm conclusions. Nonetheless, RFA seems
      superior to chemotherapy alone in patients with liver-only disease amenable for
      RFA. However, the combination of RFA and chemotherapy has been demonstrated to be
      feasible and safe, lending support to the concept of RFA followed by
      chemotherapy, in order to reduce local recurrence rates and prolong survival.

PMID- 22611345
TI  - Melanin-based coatings as lead-binding agents.
AB  - Interactions between metal ions and different forms of melanin play significant
      roles in melanin biochemistry. The binding properties of natural melanin and
      related synthetic materials can be exploited for nonbiological applications,
      potentially including water purification. A method for investigating metal ion
      melanin interactions on solid support is described, with lead as the initial
      target. 2.5 cm discs of the hydrophobic polymer PVDF were coated with synthetic
      eumelanin from the tyrosinase-catalyzed polymerization of L-dopa, and with
      melanin extracted from human hair. Lead (Pb(2+)) binding was quantified by atomic
      absorption spectroscopy (flame mode), and the data was well fit by the Langmuir
      model. Langmuir affinities ranged from 3.4 . 10(3) to 2.2 . 10(4) M(-1). At the
      maximum capacity observed, the synthetic eumelanin coating bound ~9% of its mass
      in lead. Binding of copper (Cu(2+)), zinc (Zn(2+)), and cadmium (Cd(2+)) to the
      synthetic-eumelanin-coated discs was also investigated. Under the conditions
      tested, the Langmuir affinities for Zn(2+), Cd(2+), and Cu(2+) were 35%, 53%, and
      77%, respectively, of the Langmuir affinity for Pb(2+). The synthetic-eumelanin
      coated discs have a slightly higher capacity for Cu(2+) on a per mole basis than
      for Pb(2+), and lower capacities for Cd(2+) and Zn(2+). The system described can
      be used to address biological questions and potentially be applied toward melanin
      based water purification.

PMID- 22611346
TI  - Binuclear Cu(II) and Co(II) Complexes of Tridentate Heterocyclic Shiff Base
      Derived from Salicylaldehyde with 4-Aminoantipyrine.
AB  - New binuclear Co(II) and Co(II) complexes of ONO tridentate heterocyclic Schiff
      base derived from 4-aminoantipyrine with salicylaldehyde have been synthesized
      and characterized on the bases of elemental analysis, UV-Vis., FT-IR, and also by
      aid of molar conductivity measurements, magnetic measurements, and melting
      points. It has been found that the Schiff bases with Cu(II) or Co(II) ion forming
      binuclear complexes on (1 : 1) "metal : ligand" stoichiometry. The molar
      conductance measurements of the complexes in DMSO correspond to be
      nonelectrolytic nature for all prepared complexes. Distorted octahedral
      environment is suggested for metal complexes. A theoretical treatment of the
      formation of complexes in the gas phase was studied, and this was done by using
      the HyperChem-6 program for the molecular mechanics and semi-empirical
      calculations. The free ligand and its complexes have been tested for their
      antibacterial activities against two types of human pathogenic bacteria: the
      first type (Staphylococcus aureus) is Gram positive and the second type
      (Escherichia coli) is Gram negative (by using agar well diffusion method).
      Finally, it was found that compounds show different activity of inhibition on
      growth of the bacteria.

PMID- 22611347
TI  - Synthesis, Characterization and In Vitro Antibacterial Studies of Organotin(IV)
      Complexes with 2-Hydroxyacetophenone-2-methylphenylthiosemicarbazone (H(2)dampt).
AB  - Five new organotin(IV) complexes of 2-hydroxyacetophenone-2
      methylphenylthiosemicarbazone [H(2)dampt, (1)] with formula [RSnCl(n-1)(dampt)]
      (where R = Me, n = 2 (2); R = Bu, n = 2 (3); R = Ph, n = 2 (4); R = Me(2), n = 1
      (5); R = Ph(2), n = 1 (6)) have been synthesized by direct reaction of H(2)dampt
      (1) with organotin(IV) chloride(s) in absolute methanol. The ligand (1) and its
      organotin(IV) complexes (2-6) were characterized by CHN analyses, molar
      conductivity, UV-Vis, FT-IR, (1)H, (13)C, and (119)Sn NMR spectral studies.
      H(2)dampt (1) is newly synthesized and has been structurally characterized by X
      ray crystallography. Spectroscopic data suggested that H(2)dampt (1) is
      coordinated to the tin(IV) atom through the thiolate-S, azomethine-N, and
      phenoxide-O atoms; the coordination number of tin is five. The in vitro
      antibacterial activity has been evaluated against Staphylococcus aureus,
      Enterobacter aerogenes, Escherichia coli, and Salmonella typhi. The screening
      results have shown that the organotin(IV) complexes (2-6) have better
      antibacterial activities and have potential as drugs. Furthermore, it has been
      shown that diphenyltin(IV) derivative (6) exhibits significantly better activity
      than the other organotin(IV) derivatives (2-5).

PMID- 22611348
TI  - Clinical approach for the classification of congenital uterine malformations.
AB  - A more objective, accurate and non-invasive estimation of uterine morphology is
      nowadays feasible based on the use of modern imaging techniques. The validity of
      the current classification systems in effective categorization of the female
      genital malformations has been already challenged. A new clinical approach for
      the classification of uterine anomalies is proposed. Deviation from normal
      uterine anatomy is the basic characteristic used in analogy to the American
      Fertility Society classification. The embryological origin of the anomalies is
      used as a secondary parameter. Uterine anomalies are classified into the
      following classes: 0, normal uterus; I, dysmorphic uterus; II, septate uterus
      (absorption defect); III, dysfused uterus (fusion defect); IV, unilateral formed
      uterus (formation defect); V, aplastic or dysplastic uterus (formation defect);
      VI, for still unclassified cases. A subdivision of these main classes to further
      anatomical varieties with clinical significance is also presented. The new
      proposal has been designed taking into account the experience gained from the use
      of the currently available classification systems and intending to be as simple
      as possible, clear enough and accurate as well as open for further development.
      This proposal could be used as a starting point for a working group of experts in
      the field.

PMID- 22611349
TI  - Is adenomyosis the neglected phenotype of an endomyometrial dysfunction syndrome?
AB  - Since the dissociation between adenomyoma and endometriosis in the 1920s and the
      laparoscopic progress in the diagnosis and surgery of endometriosis, the
      literature has been greatly focused on the disease endometriosis. The study of
      adenomyosis, on the other hand, has been neglected as the diagnosis remained
      based on hysterectomy specimens. However, since the introduction of magnetic
      resonance and sonographic imaging techniques in the 1980s, the myometrial
      junctional zone has been identified as a third uterine zone and interest in
      adenomyosis was renewed. This has also been the start for the interest in the
      role of the myometrial junctional zone dysfunction and adenomyosis in
      reproductive and obstetrical disorders.

PMID- 22611350
TI  - Current practice in the removal of benign endometrial polyps: a Dutch survey.
AB  - The purpose of this study is to evaluate the current practice of Dutch
      gynecologists in the removal of benign endometrial polyps and compare these
      results with the results of a previous study from 2003. In 2009 Dutch
      gynecologists were surveyed by a mailed questionnaire about polypectomy.
      Gynecologists answered questions about their individual performance of
      polypectomy: setting, form of anesthesia, method, and instrument use. The results
      were compared with the results from the previous survey. The response rate was
      70% (585 of 837 gynecologists). Among the respondents, 455 (78%) stated to remove
      endometrial polyps themselves. Polyps were mostly removed in an inpatient setting
      (337; 74%) under general or regional anesthesia (247; 54%) and under direct
      hysteroscopic vision (411; 91%). Gynecologists working in a teaching hospital
      removed polyps more often in an outpatient setting compared with gynecologists
      working in a nonteaching hospital [118 (43%) vs. 35 (19%) p < 0.001]. These
      results are in accordance with the results from 2003. Compared to 2003 there was
      an increase in the number of gynecologists performing polypectomies with local or
      no anesthesia [211 (46%) vs. 98 (22%), p < 0.001]. An increase was also noted in
      the number of gynecologists using direct hysteroscopic vision [411 (91%) vs. 290
      (64%), p < 0.001] and 5 Fr electrosurgical instruments [181 (44%) vs. 56 (19%), p
      < 0.001]. Compared to the situation in 2003, there is an increase in removal
      under direct hysteroscopic vision, with 5 Fr electrosurgical instruments, using
      local or no anesthesia. This implies there is progress in outpatient
      hysteroscopic polypectomy in the Netherlands.

PMID- 22611351
TI  - Antiviral activities and putative identification of compounds in microbial
      extracts from the Hawaiian coastal waters.
AB  - Marine environments are a rich source of significant bioactive compounds. The
      Hawaiian archipelago, located in the middle of the Pacific Ocean, hosts diverse
      microorganisms, including many endemic species. Thirty-eight microbial extracts
      from Hawaiian coastal waters were evaluated for their antiviral activity against
      four mammalian viruses including herpes simplex virus type one (HSV-1), vesicular
      stomatitis virus (VSV), vaccinia virus and poliovirus type one (poliovirus-1)
      using in vitro cell culture assay. Nine of the 38 microbial crude extracts showed
      antiviral potencies and three of these nine microbial extracts exhibited
      significant activity against the enveloped viruses. A secosteroid,
      5alpha(H),17alpha(H),(20R)-beta-acetoxyergost-8(14)-ene was putatively identified
      and confirmed to be the active compound in these marine microbial extracts. These
      results warrant future in-depth tests on the isolation of these active elements
      in order to explore and validate their antiviral potential as important
      therapeutic remedies.

PMID- 22611352
TI  - Scopararanes C-G: new oxygenated pimarane diterpenes from the marine sediment
      derived fungus Eutypella scoparia FS26.
AB  - Five new oxygenated pimarane diterpenes, named scopararanes C-G (1-5) were
      isolated from the culture of a marine sediment-derived fungus Eutypella scoparia
      FS26 obtained from the South China Sea. The structures of these compounds were
      established on the basis of extensive spectroscopic analysis. The absolute
      configurations of compounds 1-5, were determined by CD spectroscopic analysis and
      comparison with literature data. All isolated compounds (1-5) were evaluated for
      their cytotoxic activities against MCF-7, NCI-H460, and SF-268 tumor cell lines
      by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT)
      method.

PMID- 22611353
TI  - Kiamycin, a unique cytotoxic angucyclinone derivative from a marine Streptomyces
      sp.
AB  - Kiamycin (1), a new angucyclinone derivative possessing an 1,12
      epoxybenz[a]anthracene ring system, was isolated from the marine Streptomyces sp.
      strain M268 along with the known compounds 8-O-methyltetrangomycin (3) and 8-O
      methylrabelomycin (4). Their structures were elucidated by detailed spectroscopic
      analysis and comparison with literature data. The new angucyclinone derivative
      showed inhibitory activities against the human cell lines HL-60 (leukemia), A549
      (lung adenocarcinoma), and BEL-7402 (hepatoma) with inhibition rates of 68.2%,
      55.9%, and 31.7%, respectively, at 100 uM. It appears to have potential as an
      anticancer agent with selective activity.

PMID- 22611354
TI  - Activation of the dormant secondary metabolite production by introducing
      gentamicin-resistance in a marine-derived Penicillium purpurogenum G59.
AB  - A new approach to activate silent gene clusters for dormant secondary metabolite
      production has been developed by introducing gentamicin-resistance to an
      originally inactive, marine-derived fungal strain Penicillium purpurogenum G59.
      Upon treatment of the G59 spores with a high concentration of gentamicin in
      aqueous DMSO, a total of 181 mutants were obtained by single colony isolation. In
      contrast to the strain G59, the EtOAc extracts of nine mutant cultures showed
      inhibitory effects on K562 cells, indicating that the nine mutants had acquired
      capability to produce antitumor metabolites. This was evidenced by TLC and HPLC
      analysis of EtOAc extracts of G59 and the nine mutants. Further isolation and
      characterization demonstrated that four antitumor secondary metabolites,
      janthinone (1), fructigenine A (2), aspterric acid methyl ester (3) and citrinin
      (4), were newly produced by mutant 5-1-4 compared to the parent strain G59, and
      which were also not found in the secondary metabolites of other Penicillium
      purpurogenum strains. However, Compounds 1-4 inhibited the proliferation of K562
      cells with inhibition rates of 34.6% (1), 60.8% (2), 31.7% (3) and 67.1% (4) at
      100 MUg/mL, respectively. The present study demonstrated the effectiveness of a
      simple, yet practical approach to activate the production of dormant fungal
      secondary metabolites by introducing acquired resistance to aminoglycoside
      antibiotics, which could be applied to the studies for eliciting dormant
      metabolic potential of fungi to obtain cryptic secondary metabolites.

PMID- 22611355
TI  - Cellular and transcriptional responses of Crassostrea gigas hemocytes exposed in
      vitro to brevetoxin (PbTx-2).
AB  - Hemocytes mediate a series of immune reactions essential for bivalve survival in
      the environment, however, the impact of harmful algal species and their
      associated phycotoxins upon bivalve immune system is under debate. To better
      understand the possible toxic effects of these toxins, Crassostrea gigas
      hemocytes were exposed to brevetoxin (PbTx-2). Hemocyte viability, monitored
      through the neutral red retention and MTT reduction assays, and apoptosis
      (Hoechst staining) remained unchanged during 12 h of exposure to PbTx-2 in
      concentrations up to 1000 ug/L. Despite cell viability and apoptosis remained
      stable, hemocytes incubated for 4 h with 1000 ug/L of PbTx-2 revealed higher
      expression levels of Hsp70 (p < 0.01) and CYP356A1 (p < 0.05) transcripts and a
      tendency to increase FABP expression, as evaluated by Real-Time quantitative PCR.
      The expression of other studied genes (BPI, IL-17, GSTO, EcSOD, Prx6, SOD and
      GPx) remained unchanged. The results suggest that the absence of cytotoxic
      effects of PbTx-2 in Crassostrea gigas hemocytes, even at high concentrations,
      allow early defense responses to be produced by activating protective mechanisms
      associated to detoxification (CYP356A1 and possibly FABP) and stress (Hsp70), but
      not to immune or to antioxidant (BPI, IL-17, EcSOD, Prx6, GPx and SOD) related
      genes.

PMID- 22611356
TI  - A fatty acid glycoside from a marine-derived fungus isolated from mangrove plant
      Scyphiphora hydrophyllacea.
AB  - To study the antimicrobial components from the endophytic fungus A1 of mangrove
      plant Scyphiphora hydrophyllacea Gaertn. F., a new fatty acid glucoside was
      isolated by column chromatography from the broth of A1, and its structure was
      identified as R-3-hydroxyundecanoic acid methylester-3-O-alpha-l-rhamnopyranoside
      (1) by spectroscopic methods including 1D and 2D NMR (HMQC, (1)H-(1)H COSY and
      HMBC) and chemical methods. Antimicrobial assay showed compound 1 possessed
      modest inhibitory effect on Saphylococcus aureus and methicillin-resistant S.
      aureus (MRSA) using the filter paper disc agar diffusion method.

PMID- 22611357
TI  - Fucoxantin: a treasure from the sea.
AB  - The World Health Organization (WHO) estimates that 2.3 billion people will be
      overweight and 700 million obese in 2015. The reasons for this disastrous trend
      are attributed to the global tendency toward the reduced magnitude of exercise
      and physical activity and the increased dietary intake of fats, sugars and
      calories with reduced amount of vitamins and minerals. To prevent life-style
      related diseases, like Metabolic Syndrome (MS), researchers' attention is
      increasingly focusing on some of the so called "functional foods" which may be
      useful for their prevention and treatment. One of these functional ingredients is
      fucoxanthin (FX), a characteristic carotenoid present in edible brown seaweeds,
      such as Undaria pinnatifida (Wakame), Hijikia fusiformis (Hijiki), Laminaria
      japonica (Ma-Kombu) and Sargassum fulvellum. The increasing popularity of this
      molecule is certainly due to its anti-obesity effect, primarily detected by
      murine studies. These works revealed FX mediated induction of uncoupling protein
      1 (UCP-1) in abdominal white adipose tissue (WAT) mitochondria, leading to the
      oxidation of fatty acids and heat production in WAT. Beyond this important role,
      in recent studies FX has shown a great antioxidant activity, anti-cancer, anti
      diabetic and anti-photoaging properties. The aim of this review is to highlight
      the main effects of FX on human health.

PMID- 22611358
TI  - Sarcocrassocolides M-O, bioactive cembranoids from the Dongsha Atoll soft coral
      Sarcophyton crassocaule.
AB  - Three new cembranoids, sarcocrassocolides M-O (1-3), have been isolated from the
      soft coral Sarcophyton crassocaule. The structures of the metabolites were
      determined by extensive spectroscopic analysis. Compounds 1-3 were shown to
      exhibit moderate cytotoxicity toward a limited panel of cancer cell lines and
      display significant in vitro anti-inflammatory activity in LPS-stimulated
      RAW264.7 macrophage cells by inhibiting the expression of the iNOS protein.

PMID- 22611359
TI  - Chondrosterins A-E, triquinane-type sesquiterpenoids from soft coral-associated
      fungus Chondrostereum sp.
AB  - The marine fungus Chondrostereum sp. was collected from a soft coral Sarcophyton
      tortuosum from the South China Sea. This fungus was cultured in potato dextrose
      broth medium and the culture broth was extracted with EtOAc. Five new triquinane
      type sesquiterpenoids, chondrosterins A-E (1-5), and the known sesquiterpenoid
      hirsutanol C (6), were isolated. The structures were elucidated mainly on the
      basis of NMR, MS, and X-ray single-crystal diffraction data. Chondrosterin A (1)
      showed significant cytotoxic activities against cancer lines A549, CNE2, and LoVo
      with IC(50) values of 2.45, 4.95, and 5.47 MUM, respectively.

PMID- 22611360
TI  - Identification and characterization of an anti-fibrotic benzopyran compound
      isolated from mangrove-derived Streptomyces xiamenensis.
AB  - An anti-fibrotic compound produced by Streptomycesn xiamenensis, found in
      mangrove sediments, was investigated for possible therapeutic effects against
      fibrosis. The compound, N-[[3,4-dihydro-3S-hydroxy-2S-methyl-2-(4'R-methyl-3'S
      pentenyl)-2H-1-benzopyran-6-yl]carbonyl]-threonine (1), was isolated from crude
      extracts and its structure, including the absolute configuration was determined
      by extensive spectroscopic data analyses, Mosher's method, Marfey's reagent and
      quantum mechanical calculations. In terms of biological effects, this compound
      inhibits the proliferation of human lung fibroblasts (WI26), blocks adhesion of
      human acute monocytic leukemia cells (THP-1) to a monolayer of WI26 cells, and
      reduces the contractile capacity of WI26 cells in three-dimensional free-floating
      collagen gels. Altogether, these data indicate that we have identified a
      bioactive alkaloid (1) with multiple inhibitory biological effects on lung
      excessive fibrotic characteristics, that are likely involved in fibrosis,
      suggesting that this molecule might indeed have therapeutic potential against
      fibrosis.

PMID- 22611361
TI  - Isolation and structural determination of the first 8-epi-type tetrodotoxin
      analogs from the newt, Cynops ensicauda popei, and comparison of tetrodotoxin
      analogs profiles of this newt and the puffer fish, Fugu poecilonotus.
AB  - Identification of new tetrodotoxin (TTX) analogs from TTX-possessing animals
      might provide insight into its biosynthesis and metabolism. In this study, four
      new analogs, 8-epi-5,6,11-trideoxyTTX, 4,9-anhydro-8-epi-5,6,11-trideoxyTTX, 1
      hydroxy-8-epi-5,6,11-trideoxyTTX, and 1-hydroxy-4,4a-anhydro-8-epi-5,6,11
      trideoxyTTX, were isolated from the newt, Cynops ensicauda popei, and their
      structures were determined using spectroscopic methods. These are the first 8-epi
      type analogs of TTX that have been found in a natural source. Furthermore, we
      examined the composition of the TTX analogs in this newt and in the ovary of the
      puffer fish, Fugu poecilonotus, using LC/MS. The results indicate that TTX and 11
      deoxyTTX were present in both sources. However, 6-epiTTX and 8-epi-type analogs
      were detected only in the newt, while 5,6,11-trideoxyTTX was a specific and major
      analog in the puffer fish. Such considerable differences among analog
      compositions might reflect differences in the biosynthesis or metabolism of TTX
      between these animals.

PMID- 22611362
TI  - Two antimycin A analogues from marine-derived actinomycete Streptomyces
      lusitanus.
AB  - Two new antimycin A analogues, antimycin B1 and B2 (1-2), were isolated from a
      spent broth of a marine-derived bacterium, Streptomyces lusitanus. The structures
      of 1 and 2 were established on the basis of spectroscopic analyses and chemical
      methods. The isolated compounds were tested for their anti-bacterial potency.
      Compound 1 was found to be inactive against the bacteria Bacillus subtilis,
      Staphyloccocus aureus, and Loktanella hongkongensis. Compound 2 showed
      antibacterial activities against S. aureus and L. hongkongensis with MIC values
      of 32.0 and 8.0 MUg/mL, respectively.

PMID- 22611364
TI  - Invasive ductal carcinoma arising from an ectopic pancreas in the gastric wall: a
      long-term survival case.
AB  - A case of invasive ductal carcinoma of an ectopic pancreas in the stomach in a 74
      year-old woman is presented. A 4.0 cm gastric submucosal tumor (SMT) was resected
      surgically. Histologically, the tumor showed cystic tissue consisting of an
      ectopic pancreas with foci of a moderately differentiated tubular adenocarcinoma.
      In this tumor, small pancreatic tissues, acini, Langerhans islets, and ductular
      cells were detected in the gastric SMT. The patient has experienced long-term
      survival. The incidence of pancreatic cancer of an ectopic pancreas is rare, and
      the etiology of this disease is discussed in the literature.

PMID- 22611363
TI  - Severe antiretroviral therapy-induced toxic epidermal necrolysis in a child.
AB  - Toxic epidermal necrolysis (TEN) is a rare and life-threatening condition
      characterised by extensive epidermal detachment and mucosal erosion. Adverse drug
      reaction is a strongly correlated causative factor and TEN is currently
      considered the most severe end of a spectrum of drug-induced mucocutaneous
      diseases, including Stevens-Johnson syndrome. Attaining an accurate and detailed
      patient history is critical for identifying potential causative agents, which can
      prove challenging; particularly in cultures such as that of Malawi. TEN lacks
      definitive management and the use of immunomodulation, such as with
      corticosteroids and intravenous immunoglobulin, remains controversial. We report
      a fascinating case of TEN associated with antiretroviral therapy. A 10-year-old
      female was given a combination of antiretroviral drugs (lamivudine, nevirapine
      and stavudine) as postexposure prophylaxis, having been raped. The child
      subsequently developed TEN and presented to our remote hospital in Malawi, where
      she was treated entirely with supportive therapy. This is an excellent example of
      difficult disease management in a limited-resource setting and provides
      reassuring evidence to clinicians of similar circumstance. To our knowledge, this
      is the first case report of antiretroviral therapy-induced TEN in a child.

PMID- 22611365
TI  - A pleomorphic rhabdomyosarcoma mimicking an inguinal hernia: a case report and
      review of the literature.
AB  - A 59-year-old male presented with a painful right inguinal swelling and deep vein
      thrombosis at the ipsilateral leg. An inguinal hernia was initially diagnosed,
      but during surgery a large mass was found anteriorly to the peritoneal sheaths.
      Histology revealed a high-grade pleomorphic rhabdomyosarcoma. The mass advanced
      rapidly, occupying the whole right iliac fossa and metastasizing to the lung.
      Despite first- and second-line chemotherapy, the patient deteriorated rapidly and
      died. Rhabdomyosarcomas should be managed in specialized centres as they have
      prognostic factors and histologic features still controversial and poorly
      clarified.

PMID- 22611366
TI  - Presacral teratocarcinoma presenting as anal fistula and rectal adenocarcinoma: a
      unique case presentation and literature review.
AB  - Somatic malignancy arising from presacral or retroperitoneal primary teratoma is
      extremely rare. We report the case of a 37-year-old male patient with
      adenocarcinoma of respiratory type arising from primary presacral teratoma, but
      which first presented as anal fistula and rectal adenocarcinoma. The two tumors
      show the same morphology and immunophenotype (CK7-CK20+CDx2+). Malignant
      adenocarcinoma transformations from the normal respiratory epithelium are also
      found. To the best of our knowledge, this is the second case of respiratory type
      adenocarcinoma arising from primary presacral mature cystic teratoma.

PMID- 22611367
TI  - Post-Ganglionic Horner's Syndrome: An Unusual Presentation of Non-Hodgkin
      Lymphoma.
AB  - In this paper, we present the rare case of a patient with cervical
      lymphadenopathy diagnosed as a T-cell-rich B-cell non-Hodgkin lymphoma that
      manifested Horner's syndrome due to a post-ganglionic sympathetic neuron lesion
      caused by the tumor.

PMID- 22611368
TI  - Orbital aspergillosis: voriconazole - the new standard treatment?
AB  - BACKGROUND/AIM: To describe a case of invasive orbital aspergillosis and evaluate
      treatments and outcomes. METHODS: A case report and review of orbital
      aspergillosis treatment with voriconazole in the English language literature.
      CONCLUSION: Amphotericin B with debridement is the current standard of care for
      orbital aspergillosis; however, its prognosis is unfavorable. When compared to
      amphotericin B, voriconazole demonstrates a survival benefit, has less systemic
      toxicity, and is better tolerated by patients. While a prospective trial
      comparing amphotericin B to voriconazole in orbital aspergillosis is not
      feasible, there is evidence to support the use of voriconazole as primary
      therapy.

PMID- 22611369
TI  - Necrotizing keratitis after laser refractive surgery in patients with inactive
      inflammatory bowel disease.
AB  - Two cases of necrotizing keratitis following laser refractive corneal surgery,
      with stable and controlled Crohn's disease are described. A 40-year-old woman
      developed bilateral stromal inflammation and inferior thinning in the right eye
      along the flap edge within 1 day of uneventful bilateral IntraLase laser-assisted
      in situ keratomileusis. The other case is a 30-year-old man who also developed
      bilateral inferior stromal infiltrates 2 days following photorefractive
      keratectomy. Both cases were aggressively treated with systemic and topical
      corticosteroids. The infiltrates in both patients gradually resolved, with one
      relapse during the 7 months period of follow-up in the first case. These cases
      highlight the importance of taking precautions considering this and similar
      autoimmune conditions as a relative contraindication to refractive surgery.

PMID- 22611370
TI  - Tissue-based MRI intensity standardization: application to multicentric datasets.
AB  - Intensity standardization in MRI aims at correcting scanner-dependent intensity
      variations. Existing simple and robust techniques aim at matching the input image
      histogram onto a standard, while we think that standardization should aim at
      matching spatially corresponding tissue intensities. In this study, we present a
      novel automatic technique, called STI for STandardization of Intensities, which
      not only shares the simplicity and robustness of histogram-matching techniques,
      but also incorporates tissue spatial intensity information. STI uses joint
      intensity histograms to determine intensity correspondence in each tissue between
      the input and standard images. We compared STI to an existing histogram-matching
      technique on two multicentric datasets, Pilot E-ADNI and ADNI, by measuring the
      intensity error with respect to the standard image after performing nonlinear
      registration. The Pilot E-ADNI dataset consisted in 3 subjects each scanned in 7
      different sites. The ADNI dataset consisted in 795 subjects scanned in more than
      50 different sites. STI was superior to the histogram-matching technique, showing
      significantly better intensity matching for the brain white matter with respect
      to the standard image.

PMID- 22611371
TI  - On the forward scattering of microwave breast imaging.
AB  - Microwave imaging for breast cancer detection has been of significant interest
      for the last two decades. Recent studies focus on solving the imaging problem
      using an inverse scattering approach. Efforts have mainly been focused on the
      development of the inverse scattering algorithms, experimental setup, antenna
      design and clinical trials. However, the success of microwave breast imaging also
      heavily relies on the quality of the forward data such that the tumor inside the
      breast volume is well illuminated. In this work, a numerical study of the forward
      scattering data is conducted. The scattering behavior of simple breast models
      under different polarization states and aspect angles of illumination are
      considered. Numerical results have demonstrated that better data contrast could
      be obtained when the breast volume is illuminated using cross-polarized
      components in linear polarization basis or the copolarized components in the
      circular polarization basis.

PMID- 22611372
TI  - A prototype system for measuring microwave frequency reflections from the breast.
AB  - Microwave imaging of the breast is of interest for monitoring breast health, and
      approaches to active microwave imaging include tomography and radar-based
      methods. While the literature contains a growing body of work related to
      microwave breast imaging, there are only a few prototype systems that have been
      used to collect data from humans. In this paper, a prototype system for
      monostatic radar-based imaging that has been used in an initial study measuring
      reflections from volunteers is discussed. The performance of the system is
      explored by examining the mechanical positioning of sensor, as well as microwave
      measurement sensitivity. To gain insight into the measurement of reflected
      signals, simulations and measurements of a simple phantom are compared and
      discussed in relation to system sensitivity. Finally, a successful scan of a
      volunteer is described.

PMID- 22611373
TI  - Increased caspase-3 immunoreactivity of erythrocytes in STZ diabetic rats.
AB  - Eryptosis is a term to define apoptosis of erythrocytes. Oxidative stress and
      hyperglycemia, both of which exist in the diabetic intravascular environment, can
      trigger eryptosis of erythrocytes. In this experimental study, it is presented
      that the majority of erythrocytes shows caspase-3 immunoreactivity in
      streptozocin- (STZ)-induced diabetic rats. Besides that, caspase-3 positive
      erythrocytes are aggregated and attached to vascular endothelium. In conclusion,
      these results may start a debate that eryptosis could have a role in the diabetic
      complications.

PMID- 22611374
TI  - Spontaneous periodontitis development in diabetic rats involves an unrestricted
      expression of inflammatory cytokines and tissue destructive factors in the
      absence of major changes in commensal oral microbiota.
AB  - Diabetes mellitus is a heterogeneous group of disorders, in which hyperglycemia
      is a main feature. The objective was to evaluate the involvement of RAGE,
      inflammatory cytokines, and metalloproteinases in spontaneous periodontitis
      triggered by diabetes induction. Immunohistochemical procedures for MMP-2, MMP-9,
      TNF-alpha, IL-1beta, IL-6, RANKL, and RAGE were performed in rats after 1, 3, 6,
      9, and 12 months of diabetes induction. Total DNA was extracted from paraffin
      embedded tissues and evaluated by Real-TimePCR for 16S total bacterial load and
      specific periodontopathogens. Our data did not demonstrate differences in
      microbiological patterns between groups. In diabetic groups, an increase in RAGE
      positive cells was detected at 6, 9, and 12 months, while TNF-alpha-stained cells
      were more prevalent at 6 and 12 months. In experimental groups, IL-beta-positive
      cells were increased after 12 months, IL-6 stained cells were increased at 9 and
      12 months, and RANKL-positive cells at 9 months. Diabetes resulted in widespread
      expression of RAGE, followed by expression of proinflammatory mediators, without
      major alterations in oral microbial profile. The pervasive expression of
      cytokines suggests that spontaneous periodontitis development may be independent
      of microbial stimulation and may be triggered by diabetes-driven imbalance of
      homeostasis.

PMID- 22611375
TI  - Small molecule drug discovery at the glucagon-like peptide-1 receptor.
AB  - The therapeutic success of peptide glucagon-like peptide-1 (GLP-1) receptor
      agonists for the treatment of type 2 diabetes mellitus has inspired discovery
      efforts aimed at developing orally available small molecule GLP-1 receptor
      agonists. Although the GLP-1 receptor is a member of the structurally complex
      class B1 family of GPCRs, in recent years, a diverse array of orthosteric and
      allosteric nonpeptide ligands has been reported. These compounds include
      antagonists, agonists, and positive allosteric modulators with intrinsic
      efficacy. In this paper, a comprehensive review of currently disclosed small
      molecule GLP-1 receptor ligands is presented. In addition, examples of "ligand
      bias" and "probe dependency" for the GLP-1 receptor are discussed; these emerging
      concepts may influence further optimization of known molecules or persuade
      designs of expanded screening strategies to identify novel chemical starting
      points for GLP-1 receptor drug discovery.

PMID- 22611376
TI  - Cholesterol-lowering probiotics as potential biotherapeutics for metabolic
      diseases.
AB  - Cardiovascular diseases are one of the major causes of deaths in adults in the
      western world. Elevated levels of certain blood lipids have been reported to be
      the principal cause of cardiovascular disease and other disabilities in developed
      countries. Several animal and clinical trials have shown a positive association
      between cholesterol levels and the risks of coronary heart disease. Current
      dietary strategies for the prevention of cardiovascular disease advocate
      adherence to low-fat/low-saturated-fat diets. Although there is no doubt that, in
      experimental conditions, low-fat diets offer an effective means of reducing blood
      cholesterol concentrations on a population basis, these appear to be less
      effective, largely due to poor compliance, attributed to low palatability and
      acceptability of these diets to the consumers. Due to the low consumer
      compliance, attempts have been made to identify other dietary components that can
      reduce blood cholesterol levels. Supplementation of diet with fermented dairy
      products or lactic acid bacteria containing dairy products has shown the
      potential to reduce serum cholesterol levels. Various approaches have been used
      to alleviate this issue, including the use of probiotics, especially
      Bifidobacterium spp. and Lactobacillus spp.. Probiotics, the living
      microorganisms that confer health benefits on the host when administered in
      adequate amounts, have received much attention on their proclaimed health
      benefits which include improvement in lactose intolerance, increase in natural
      resistance to infectious disease in gastrointestinal tract, suppression of
      cancer, antidiabetic, reduction in serum cholesterol level, and improved
      digestion. In addition, there are numerous reports on cholesterol removal ability
      of probiotics and their hypocholesterolemic effects. Several possible mechanisms
      for cholesterol removal by probiotics are assimilation of cholesterol by growing
      cells, binding of cholesterol to cellular surface, incorporation of cholesterol
      into the cellular membrane, deconjugation of bile via bile salt hydrolase,
      coprecipitation of cholesterol with deconjugated bile, binding action of bile by
      fibre, and production of short-chain fatty acids by oligosaccharides. The present
      paper reviews the mechanisms of action of anti-cholesterolemic potential of
      probiotic microorganisms and probiotic food products, with the aim of lowering
      the risks of cardiovascular and coronary heart diseases.

PMID- 22611378
TI  - Effect of ursodeoxycholic Acid alone and ursodeoxycholic Acid plus domperidone on
      radiolucent gallstones and gallbladder contractility in humans.
AB  - Background/Aims. The aim of this study was to compare the effects of
      ursodeoxycholic acid (UDCA) alone and UDCA plus domperidone on dissolution of
      solitary or multiple gallstones. Methods. Fifty-three patients with cholesterol
      gallstones were randomized into three treatment groups: group I (n = 22) was
      given UDCA (15 mg/kg/day) alone and group II (n = 18) was treated with
      domperidone (30 mg/day) in addition to UDCA. The control group (n = 13) was
      followed without a medical treatment. Gallbladder volumes and ejection fractions
      were measured sonographically in all patients before and after treatment.
      Results. After 12 months of treatment, stone dissolution was found in 9 (40.9%)
      of the patients in group I and 7 (38.8%) of the patients in group II. The
      difference was statistically significant compared to controls in both treatment
      groups (P < 0.05) but the two groups did not show a difference between each other
      (P > 0.05). All the patients that achieved dissolution had multiple gallstones
      except for one patient with a solitary stone in group I. Neither monotherapy of
      UDCA nor the combination with domperidone affected the ejection fraction of
      gallbladder. Conclusions. Combination with domperidone did not potentiate the
      efficacy of UDCA. It has been observed that both UDCA alone and UDCA plus
      domperidone treatment did not affect ejection fraction of gallbladder.

PMID- 22611377
TI  - Evolutionary history of LTR retrotransposon chromodomains in plants.
AB  - Chromodomain-containing LTR retrotransposons are one of the most successful
      groups of mobile elements in plant genomes. Previously, we demonstrated that two
      types of chromodomains (CHDs) are carried by plant LTR retrotransposons.
      Chromodomains from group I (CHD_I) were detected only in Tcn1-like LTR
      retrotransposons from nonseed plants such as mosses (including the model moss
      species Physcomitrella) and lycophytes (the Selaginella species). LTR
      retrotransposon chromodomains from group II (CHD_II) have been described from a
      wide range of higher plants. In the present study, we performed computer-based
      mining of plant LTR retrotransposon CHDs from diverse plants with an emphasis on
      spike-moss Selaginella. Our extended comparative and phylogenetic analysis
      demonstrated that two types of CHDs are present only in the Selaginella genome,
      which puts this species in a unique position among plants. It appears that a
      transition from CHD_I to CHD_II and further diversification occurred in the
      evolutionary history of plant LTR retrotransposons at approximately 400 MYA and
      most probably was associated with the evolution of chromatin organization.

PMID- 22611379
TI  - TREM-1 Promotes Pancreatitis-Associated Intestinal Barrier Dysfunction.
AB  - Severe acute pancreatitis (SAP) can cause intestinal barrier dysfunction (IBD),
      which significantly increases the disease severity and risk of mortality. We
      hypothesized that the innate immunity- and inflammatory-related protein
      triggering receptor expressed on myeloid cells-1 (TREM-1) contributes to this
      complication of SAP. Thus, we investigated the effect of TREM-1 pathway
      modulation on a rat model of pancreatitis-associated IBD. In this study we sought
      to clarify the role of TREM-1 in the pathophysiology of intestinal barrier
      dysfunction in SAP. Specifically, we evaluated levels of serum TREM-1 and
      membrane-bound TREM-1 in the intestine and pancreas from an animal model of
      experimentally induced SAP. TREM-1 pathway blockade by LP17 treatment may
      suppress pancreatitis-associated IBD and ameliorate the damage to the intestinal
      mucosa barrier.

PMID- 22611380
TI  - Biomarkers of oxidative stress and personalized treatment of pulmonary
      tuberculosis: emerging role of gamma-glutamyltransferase.
AB  - Background. The objectives were (i) to evaluate the impact of acute pulmonary
      tuberculosis (PTB) and anti-TB therapy on the relationship between AST, ALT, and
      GGT levels in absence of conditions related to hepatotoxicity; (ii) to evaluate
      the rate and the time of alterations of AST, ALT, and GGT. Design and Methods. A
      prospective followup of 40 adults (21 males; mean age of 34.7 +/- 5.8 years) with
      active PTB on initial phase and continuation phase anti-TB. Results. Only 3% (n =
      1) developed a transient and benign ADR at day 30 without interruption of anti-TB
      treatment. Within normal ranges, GGT decreased significantly from day 0 to day
      60, while AST and ALT increased significantly and respectively. During day 0-day
      60, there was a significant, negative, and independent association between GGT
      and AST. Conclusion. The initial two months led to significant improvement of
      oxidative stress. Values of oxidative markers in normal ranges might predict low
      rate of ADR.

PMID- 22611382
TI  - Post-radical-prostatectomy urinary incontinence: the management of concomitant
      bladder neck contracture.
AB  - Urinary incontinence postradical prostatectomy is a common problem which
      adversely affects quality of life. Concomitant bladder neck contracture in the
      setting of postprostatectomy incontinence represents a challenging clinical
      problem. Postprostatectomy bladder neck contracture is frequently recurrent and
      makes surgical management of incontinence difficult. The aetiology of bladder
      neck contracture and what constitutes the optimum management strategy are
      controversial. Here we review the literature and also present our approach.

PMID- 22611381
TI  - The Anti-Inflammatory, Phytoestrogenic, and Antioxidative Role of Labisia pumila
      in Prevention of Postmenopausal Osteoporosis.
AB  - Osteoporosis is characterized by skeletal degeneration with low bone mass and
      destruction of microarchitecture of bone tissue which is attributed to various
      factors including inflammation. Women are more likely to develop osteoporosis
      than men due to reduction in estrogen during menopause which leads to decline in
      bone-formation and increase in bone-resorption activity. Estrogen is able to
      suppress production of proinflammatory cytokines such as IL-1, IL-6, IL-7, and
      TNF-alpha. This is why these cytokines are elevated in postmenopausal women.
      Studies have shown that estrogen reduction is able to stimulate focal
      inflammation in bone. Labisia pumila (LP) which is known to exert phytoestrogenic
      effect can be used as an alternative to ERT which can produce positive effects on
      bone without causing side effects. LP contains antioxidant as well as exerting
      anti-inflammatory effect which can act as free radical scavenger, thus inhibiting
      TNF-alpha production and COX-2 expression which leads to decline in RANKL
      expression, resulting in reduction in osteoclast activity which consequently
      reduces bone loss. Hence, it is the phytoestrogenic, anti-inflammatory, and
      antioxidative properties that make LP an effective agent against osteoporosis.

PMID- 22611383
TI  - Port-site metastasis after laparoscopic surgery for urological malignancy:
      forgotten or missed.
AB  - Purpose. Port-site metastasis has been a concern with the common use of
      laparoscopy in urologic oncology. We conducted this study to provide a review of
      port-site metastases reported after the laparoscopy in managing urologic
      malignancies, possible contributing factors and preventative measures. Materials
      and Methods. An electronic search of MEDLINE using the combined MESH key words
      "port-site metastasis" and "Urology". Results. 51 articles addressing port-site
      metastasis after laparoscopic surgery for urolo!gical malignancy were identified.
      Conclusion. Port-site metastasis after laparoscopic surgery for urolo!gical
      malignancy is rare. The incidence is comparable to the rate for surgical wound
      metastases.

PMID- 22611384
TI  - Interactive tele-radiological segmentation systems for treatment and diagnosis.
AB  - Telehealth is the exchange of health information and the provision of health care
      services through electronic information and communications technology, where
      participants are separated by geographic, time, social and cultural barriers. The
      shift of telemedicine from desktop platforms to wireless and mobile technologies
      is likely to have a significant impact on healthcare in the future. It is
      therefore crucial to develop a general information exchange e-medical system to
      enables its users to perform online and offline medical consultations through
      diagnosis. During the medical diagnosis, image analysis techniques combined with
      doctor's opinions could be useful for final medical decisions. Quantitative
      analysis of digital images requires detection and segmentation of the borders of
      the object of interest. In medical images, segmentation has traditionally been
      done by human experts. Even with the aid of image processing software (computer
      assisted segmentation tools), manual segmentation of 2D and 3D CT images is
      tedious, time-consuming, and thus impractical, especially in cases where a large
      number of objects must be specified. Substantial computational and storage
      requirements become especially acute when object orientation and scale have to be
      considered. Therefore automated or semi-automated segmentation techniques are
      essential if these software applications are ever to gain widespread clinical
      use. The main purpose of this work is to analyze segmentation techniques for the
      definition of anatomical structures under telemedical systems.

PMID- 22611385
TI  - Lung physiology and obesity: anesthetic implications for thoracic procedures.
AB  - Obesity is a worldwide health problem affecting 34% of the American population.
      As a result, more patients requiring anesthesia for thoracic surgery will be
      overweight or obese. Changes in static and dynamic respiratory mechanics, upper
      airway anatomy, as well as multiple preoperative comorbidities and altered drug
      metabolism, characterize obese patients and affect the anesthetic plan at
      multiple levels. During the preoperative evaluation, patients should be assessed
      to identify who is at risk for difficult ventilation and intubation, and
      postoperative complications. The analgesia plan should be executed starting in
      the preoperative area, to increase the success of extubation at the end of the
      case and prevent reintubation. Intraoperative ventilatory settings should be
      customized to the changes in respiratory mechanics for the specific patient and
      procedure, to minimize the risk of lung damage. Several non invasive ventilatory
      modalities are available to increase the success rate of extubation at the end of
      the case and to prevent reintubation. The goal of this review is to evaluate the
      physiological and anatomical changes associated with obesity and how they affect
      the multiple components of the anesthetic management for thoracic procedures.

PMID- 22611386
TI  - Evaluation of fluid responsiveness: is photoplethysmography a noninvasive
      alternative?
AB  - Background. Goal-directed fluid therapy reduces morbidity and mortality in
      various clinical settings. Respiratory variations in photoplethysmography are
      proposed as a noninvasive alternative to predict fluid responsiveness during
      mechanical ventilation. This paper aims to critically evaluate current data on
      the ability of photoplethysmography to predict fluid responsiveness. Method.
      Primary searches were performed in PubMed, Medline, and Embase on November 10,
      2011. Results. 14 papers evaluating photoplethysmography and fluid responsiveness
      were found. Nine studies calculated areas under the receiver operating
      characteristic curves for DeltaPOP (>0.85 in four, 0.75-0.85 in one, and <0.75 in
      four studies) and seven for PVI (values ranging from 0.54 to 0.98). Correlations
      between DeltaPOP/PVI and DeltaPP/other dynamic variables vary substantially.
      Conclusion. Although photoplethysmography is a promising technique, predictive
      values and correlations with other hemodynamic variables indicating fluid
      responsiveness vary substantially. Presently, it is not documented that
      photoplethysmography is adequately valid and reliable to be included in clinical
      practice for evaluation of fluid responsiveness.

PMID- 22611387
TI  - Oxidative Stress and Mitochondrial Dysfunction in Down's Syndrome: Relevance to
      Aging and Dementia.
AB  - Genome-wide gene deregulation and oxidative stress appear to be critical factors
      determining the high variability of phenotypes in Down's syndrome (DS). Even
      though individuals with trisomy 21 exhibit a higher survival rate compared to
      other aneuploidies, most of them die in utero or early during postnatal life.
      While the survivors are currently predicted to live past 60 years, they suffer
      higher incidence of age-related conditions including Alzheimer's disease (AD).
      This paper is centered on the mechanisms by which mitochondrial factors and
      oxidative stress may orchestrate an adaptive response directed to maintain basic
      cellular functions and survival in DS. In this context, the timing of therapeutic
      interventions should be carefully considered for the successful treatment of
      chronic disorders in the DS population.

PMID- 22611388
TI  - Sarcopenic obesity and cognitive functioning: the mediating roles of insulin
      resistance and inflammation?
AB  - This study examined the influence of insulin resistance and inflammation on the
      association between body composition and cognitive performance in older adults,
      aged 60-69 and aged 70 and older. Subjects included 1127 adults from NHANES 1999
      2002. Body composition was categorized based on measurements of muscle mass and
      waist circumference as sarcopenic nonobese, nonsarcopenic obese, sarcopenic
      obese, and normal. Using OLS regression models, our findings suggest body
      composition is not associated with cognitive functioning in adults ages 60-69;
      however, for adults aged 70 and over, sarcopenia and obesity, either
      independently or concurrently, were associated with worse cognitive functioning
      relative to non-sarcopenic non-obese older adults. Furthermore, insulin
      resistance accounted for a significant proportion of the relationship between
      cognitive performance and obesity, with or without sarcopenia. Additionally,
      although high CRP was significantly associated with poorer cognitive functioning
      in adults ages 60-69, it did not influence the association between body
      composition and cognitive performance. This study provides evidence that age
      related physiological maladaptations, such as metabolic deregulation, which are
      associated with abdominal fat, may simultaneously contribute to lower cognition
      and muscle mass, reflecting a degradation of multiple physiological systems.

PMID- 22611389
TI  - Factors Associated with Late Presentation of HIV and Estimation of Antiretroviral
      Treatment Need according to CD4 Lymphocyte Count in a Resource-Limited Setting:
      Data from an HIV Cohort Study in India.
AB  - We describe the CD4 lymphocyte count at HIV presentation in an HIV cohort from a
      rural district of India. The majority of patients were diagnosed for their HIV
      related symptoms, although a sizeable proportion of women were diagnosed because
      of antenatal screening or for having an HIV-positive partner. Patients diagnosed
      of HIV for antenatal screening or having an HIV-positive sexual partner had
      higher CD4 lymphocyte count than patients having tuberculosis or HIV-related
      symptoms. The proportion of patients diagnosed with CD4 count <200 and <350
      cells/mm(3) were 46% and 68.7%, respectively, and these figures did not change
      during the five years of the study. Factors associated with late presentations
      were male sex, older age, not having a permanent house, and, in women, lower
      education and being a widow or separated. With the implementation of 2010 WHO
      guidelines, the number of newly diagnosed patients who will require HIV treatment
      will increase 13.8%. If the CD4 count threshold for initiating HIV treatment is
      increased from 350 to 500 cells/mm(3), the number of patients in need of
      treatment would increase 15.7%. Therefore, new strategies for avoiding HIV late
      presentation are urgently needed in developing countries.

PMID- 22611390
TI  - In memoriam: Wylie Vale, Jr., Ph.D. (1941-2012).

PMID- 22611391
TI  - Editorial: molecular endocrinology articles in the spotlight for June 2012.

PMID- 22611393
TI  - Generation of transplantable Beta cells for patient-specific cell therapy.
AB  - Islet cell transplantation offers a potential cure for type 1 diabetes, but it is
      challenged by insufficient donor tissue and side effects of current
      immunosuppressive drugs. Therefore, alternative sources of insulin-producing
      cells and isletfriendly immunosuppression are required to increase the efficiency
      and safety of this procedure. Beta cells can be transdifferentiated from
      precursors or another heterologous (non-beta-cell) source. Recent advances in
      beta cell regeneration from somatic cells such as fibroblasts could circumvent
      the usage of immunosuppressive drugs. Therefore, generation of patient-specific
      beta cells provides the potential of an evolutionary treatment for patients with
      diabetes.

PMID- 22611394
TI  - Quality of Life, Wishes, and Needs in Women with Gestational Diabetes: Italian
      DAWN Pregnancy Study.
AB  - The DAWN (Diabetes Attitudes, Wishes and Needs) study is a survey promoted by the
      International Diabetes Federation to recognize the perceptions and attitudes of
      people suffering from diabetes mellitus. In this context, we evaluated the
      quality of life of Italian and immigrant women with gestational diabetes mellitus
      (GDM). Information was gathered using a structured questionnaire for patients'
      self-compilation. In a 3-month period, a 51-item questionnaire was submitted to
      198 Italians and 88 immigrants (from 27 different foreign nationalities). Italian
      women were older and had higher education than the immigrants. 60% of the
      Italians and 38% of the immigrants had a family history of diabetes mellitus. In
      both groups, the diagnosis of GDM caused anxiety; one-third of women feared their
      child could contract diabetes at delivery and/or have congenital malformations.
      Some women had trouble in following treatment regimens: the major concern being
      dietary advice and blood glucose testing. Most women were satisfied (34%) or
      highly satisfied (60%) with the quality of care, although the degree of
      cooperation between diabetes specialists and gynaecologists was considered
      sometimes unsatisfactory. In order to optimize maternal and foetal outcomes,
      educational projects and improved communication between patients and the
      healthcare provider team are recommended.

PMID- 22611395
TI  - Antibody-Dependent Cellular Cytotoxicity and NK Cell-Driven Immune Escape in HIV
      Infection: Implications for HIV Vaccine Development.
AB  - The HIV-1 genome is malleable and a difficult target tot vaccinate against. It
      has long been recognised that cytotoxic T lymphocytes and neutralising antibodies
      readily select for immune escape HIV variants. It is now also clear that NK cells
      can also select for immune escape. NK cells force immune escape through both
      direct Killer-immunoglobulin-like receptor (KIR)-mediated killing as well as
      through facilitating antibody-dependent cellular cytotoxicity (ADCC). These newer
      finding suggest NK cells and ADCC responses apply significant pressure to the
      virus. There is an opportunity to harness these immune responses in the design of
      more effective HIV vaccines.

PMID- 22611397
TI  - Electrospray ionization mass spectrometry: a technique to access the information
      beyond the molecular weight of the analyte.
AB  - The Electrospray Ionization (ESI) is a soft ionization technique extensively used
      for production of gas phase ions (without fragmentation) of thermally labile
      large supramolecules. In the present review we have described the development of
      Electrospray Ionization mass spectrometry (ESI-MS) during the last 25 years in
      the study of various properties of different types of biological molecules. There
      have been extensive studies on the mechanism of formation of charged gaseous
      species by the ESI. Several groups have investigated the origin and implications
      of the multiple charge states of proteins observed in the ESI-mass spectra of the
      proteins. The charged analytes produced by ESI can be fragmented by activating
      them in the gas-phase, and thus tandem mass spectrometry has been developed,
      which provides very important insights on the structural properties of the
      molecule. The review will highlight recent developments and emerging directions
      in this fascinating area of research.

PMID- 22611398
TI  - Potential role of drebrin a, an f-actin binding protein, in reactive synaptic
      plasticity after pilocarpine-induced seizures: functional implications in
      epilepsy.
AB  - Several neurological disorders characterized by cognitive deficits, including
      Alzheimer's disease, down syndrome, and epilepsy exhibit abnormal spine density
      and/or morphology. Actin-based cytoskeleton network dynamics is critical for the
      regulation of spine morphology and synaptic function. In this paper, I consider
      the functions of drebrin A in cell shaping, spine plasticity, and synaptic
      function. Developmentally regulated brain protein (drebrin A) is one of the most
      abundant neuron-specific binding proteins of F-actin and its expression is
      increased in parallel with synapse formation. Drebrin A is particularly
      concentrated in dendritic spines receiving excitatory inputs. Our recent findings
      point to a critical role of DA in dendritic spine structural integrity and
      stabilization, likely via regulation of actin cytoskeleton dynamics, and
      glutamatergic synaptic function that underlies the development of spontaneous
      recurrent seizures in pilocarpine-treated animals. Further research into this
      area may provide useful insights into the pathology of status epilepticus and
      epileptogenic mechanisms and ultimately may provide the basis for future
      treatment options.

PMID- 22611400
TI  - A Micro-RNA Connection in BRaf(V600E)-Mediated Premature Senescence of Human
      Melanocytes.
AB  - Recent high-throughput-sequencing of the cancer genome has identified oncogenic
      mutations in BRaf genetic locus as one of the critical events in melanomagenesis.
      In normal cells, the activity of BRaf is tightly regulated. Gain-of-function
      mutations like those identified in melanoma frequently lead to enhanced cell
      survival and unrestrained growth. The activating mutation of BRaf will also
      induce the cells to senesce. However, the mechanism by which the oncogenic BRaf
      induces the senescent barrier remains poorly defined. microRNAs have regulatory
      functions toward the expression of genes that are important in carcinogenesis.
      Here we show that expression of several microRNAs is altered when the oncogenic
      version of BRaf is introduced in cultured primary melanocytes and these cells
      undergo premature cellular senescence. These include eight microRNAs whose
      expression rates are significantly stimulated and three that are repressed. While
      most of the induced microRNAs have documented negative effects on cell cycle
      progression, one of the repressed microRNAs has proven oncogenic functions.
      Ectopic expression of some of these induced microRNAs increased the expression of
      senescence markers and induced growth arrest and senescence in primary
      melanocytes. Taken together, our results suggest that the change in microRNA
      expression rates may play a vital role in senescence induced by the oncogenic
      BRaf.

PMID- 22611401
TI  - Aggressive B-cell lymphomas.

PMID- 22611402
TI  - Relationship between the Presence of the nalC Mutation and Multidrug Resistance
      in Pseudomonas aeruginosa.
AB  - Objectives. The current study was conducted to determine the relationship between
      the presences of significant multidrug resistance in Pseudomonas aeruginosa (P.
      aeruginosa) having intact mexR genes (nalC) to different antibiotics. Methods. In
      order to identify nalC, fifty strains of P. aeruginosa were obtained. All
      isolates were found in urinary tract infections. They were evaluated against
      different antibiotics. The nalC mutant was identified by PCR. Results. The 50
      clinical isolates of P. aeruginosa originated from two hospitals in Iran, in
      which 32 isolates were found in Milad hospital, and 18 isolates were collected in
      the Ilam Hospital. The results in Milad hospital of nalC revealed that all P.
      aeruginosa resistant to oxacillin showed the presence of nalC. In Ilam hospital
      only three (16.6%) isolates were resistant to oxacilin and aztreonam, and among
      these three isolates only one isolate revealed resistance to ceftazidime and
      amikacin. The resistant isolates showed the presence of both OXA-10 and nalC.
      Conclusion. Our results showed that the presence of nalC was observed among P.
      aeruginosa resistance to oxacilin. Thus, the finding suggested relationship
      between oxacilin resistance and presence of nalC and consequently overproduction
      of the MexABOprM efflux system.

PMID- 22611403
TI  - Cystic Fibrosis: Brazilian ENT Experience.
AB  - Most published studies about Cystic Fibrosis (CF) are European or North American.
      There are still few publications about the characteristics of fibrocystic
      populations in developing countries. The incidence of cystic fibrosis (CF) in
      Brazil varies among different regions (1 : 10,000 in Minas Gerais, 1 : 9,500 in
      Parana, 1 : 8,700 in Santa Catarina, and 1 : 1600 in Rio Grande do Sul). The
      prevalence of the DF508 mutation also varies according to population: 33% in Sao
      Paulo, 49% in Rio Grande do Sul, 27% in Santa Catarina, and 52% in Minas Gerais.
      Cough and nasal obstruction are the most common symptoms. The variation in nasal
      polyposis prevalence may be explained by population genotypic characteristics in
      a country that spans a continent. Findings on nasal endoscopy and computed
      tomography (CT) have better correlation than do this information compared with
      surgical and clinical history. Microbiologic studies suggest a high level of
      early contamination of the airways. Sensorineural hearing loss (SNHL) occurs in
      these patients as a result of ototoxic antibiotics. The data compiled in this
      paper is useful, but also lead to the general agreement that more research would
      be welcome due to the unique characteristics of this country.

PMID- 22611404
TI  - Assessment of Single-Word Production for Children under Three Years of Age:
      Comparison of Children with and without Cleft Palate.
AB  - Background. This study reports comparative phonological assessment results for
      children with cleft lip and/or palate (CLP) to typically developing peers using
      an evaluation tool for early phonological skills. Methods. Children without
      clefts (NC = noncleft) and 24 children with CLP, ages of 18-36 months, were
      evaluated using the Profile of Early Expressive Phonological Skills (PEEPSs) [1].
      Children interacted with toy manipulatives to elicit a representative sample of
      target English consonants and syllable structures that are typically acquired by
      children between 18 and 27 months of age. Results. Results revealed significant
      differences between the two groups with regard to measures of consonant
      inventory, place of articulation, manner of production, accuracy, and error
      patterns. Syllable structure did not indicate differences, with the exception of
      initial consonant clusters. Conclusions. findings provide support for PEEPS as a
      viable option for single-word assessment of children with CLP prior to 3 years of
      age.

PMID- 22611399
TI  - Untethering the nuclear envelope and cytoskeleton: biologically distinct
      dystonias arising from a common cellular dysfunction.
AB  - Most cases of early onset DYT1 dystonia in humans are caused by a GAG deletion in
      the TOR1A gene leading to loss of a glutamic acid (DeltaE) in the torsinA
      protein, which underlies a movement disorder associated with neuronal dysfunction
      without apparent neurodegeneration. Mutation/deletion of the gene (Dst) encoding
      dystonin in mice results in a dystonic movement disorder termed dystonia
      musculorum, which resembles aspects of dystonia in humans. While torsinA and
      dystonin proteins do not share modular domain architecture, they participate in a
      similar function by modulating a structural link between the nuclear envelope and
      the cytoskeleton in neuronal cells. We suggest that through a shared interaction
      with the nuclear envelope protein nesprin-3alpha, torsinA and the neuronal
      dystonin-a2 isoform comprise a bridge complex between the outer nuclear membrane
      and the cytoskeleton, which is critical for some aspects of neuronal development
      and function. Elucidation of the overlapping roles of torsinA and dystonin-a2 in
      nuclear/endoplasmic reticulum dynamics should provide insights into the cellular
      mechanisms underlying the dystonic phenotype.

PMID- 22611405
TI  - Effects of xinfeng capsules on expression of platelet granule membrane protein
      140 and platelet cluster of differentiation 40 ligand in peripheral blood of
      adjuvant arthritis rats.
AB  - Platelet GMP-140 and CD40L as specific markers of platelet activation play an
      important role in the morbidity and development of rheumatoid arthritis. The
      expression of GMP-140, CD40L increases in peripheral blood of AA rats. And they
      have correlation with voix pedis' swelling, AI. XFC could inhibit the
      inflammatory response through inhibiting platelet activation of AA rats, which
      means decreasing the expression of GMP-140, CD40L in peripheral blood. So, the
      voix pedis' swelling and AI were decreased as the result.

PMID- 22611406
TI  - Development of an IgG4-RD Responder Index.
AB  - IgG4-related disease (IgG4-RD) is a multiorgan inflammatory disease in which
      diverse organ manifestations are linked by common histopathological and
      immunohistochemical features. Prospective studies of IgG4-RD patients are
      required to clarify the natural history, long-term prognosis, and treatment
      approaches in this recently recognized condition. Patients with IgG4-RD have
      different organ manifestations and are followed by multiple specialties.
      Divergent approaches to the assessment of patients can complicate the
      interpretation of studies, emphasizing the critical need for validated outcome
      measures, particularly assessments of disease activity and response to treatment.
      We developed a prototype IgG4-RD Responder Index (IgG4-RD RI) based on the
      approach used in the development of the Birmingham Vasculitis Activity Score for
      Wegener's granulomatosis (BVAS/WG). The IgG4-RD RI was refined by members of the
      International IgG4-RD Symposium Organizing Committee in a paper case exercise.
      The revised instrument was applied retrospectively to fifteen IgG4-RD patients at
      our institution. Those scores were compared to physician's global assessment
      scale for the same visits. This paper describes the philosophy and goals of the
      IgG4-RD RI, the steps in the development of this instrument to date, and future
      plans for validation of this instrument as an outcome measure.

PMID- 22611407
TI  - A Report of Nausea and Vomiting with Discontinuation of Chronic Use of Salvia
      divinorum.
AB  - Introduction. This is the first reported case of gastrointestinal symptoms
      associated with withdrawal after chronic use of this substance. Case
      Presentation. A 51-year-old Caucasian woman was referred to a hospital with a 3
      day history of nausea, vomiting, diarrhea, and abdominal discomfort. She reported
      no sick family members or contact with anyone who was ill. She did report smoking
      3-5 cigarettes of the herb "Salvia" consistently for 3-4 months and quit
      approximately 48 hours before symptoms appeared. Her use of the herb had been
      consistent; she smoked several cigarettes each day. Laboratory results were
      essentially normal including the white blood cell count. She received symptomatic
      treatment and was released after one day. Discussion. Salvinorin A, a kappa
      opioid receptor agonist, is the major active ingredient of S. divinorum. The
      unique opioid properties of this herb may explain its ability to cause changes in
      intestinal transit time. Conclusion. A 51-year-old woman possibly developed
      gastrointestinal manifestations suggestive of withdrawal from Salvia divinorum
      after smoking the substance consistently for 3 to 4 months. The widespread use of
      this herb will make the potential for withdrawal syndromes more commonplace.

PMID- 22611408
TI  - Staged, open, no-ischemia nephron-sparing surgery for bilateral-multiple kidney
      tumors in a patient with birt-hogg-dube syndrome.
AB  - Hereditary kidney cancer patients with bilateral multiple kidney tumors represent
      challenges in the era of rapidly growing minimal invasive treatment techniques.
      Birt-Hogg-Dube Syndrome (BHDS) is an autosomal dominant genodermatosis
      characterized by a triad of benign skin tumors (fibrofolliculomas,
      trichodiscomas, acrochordons) together with an increased risk of developing
      malignant renal tumors and pulmonary disease such as pneumothoraces and multiple
      lung cysts. The morbidity and mortality of the affected patients is determined by
      the presence of the kidney tumors, which tend to be multifocal and bilateral, as
      observed in other hereditary kidney cancer syndromes like von Hippel-Lindau
      disease, familial leiomyomatosis, and hereditary papillary renal cell carcinoma.
      Herein, a patient with BHDS, presenting with synchronous bilateral multiple
      kidney tumors, is reported. The report describes the management of kidney tumors
      with two-stage open nephron-sparing surgery in which the nonvascular clamping
      technique was utilized.

PMID- 22611409
TI  - Complete remission of human parvovirus b19 associated symptoms by loxoprofen in
      patients with atopic predispositions.
AB  - Two cases of women in their thirties with past histories of atopic dermatitis and
      allergic rhinitis developed a low grade fever, followed by a butterfly-shaped
      erythema, swelling of their fingers, and polyarthralgia. Despite such symptoms
      that overlap with those of systemic lupus erythematosus (SLE), the diagnostic
      criteria for SLE were not fulfilled. Due to positive results for human parvovirus
      B19 (HPV-B19) IgM antibodies in the serum, diagnoses of HPV-B19 infection were
      made in both cases. Although acetaminophen failed to improve their deteriorating
      symptoms, a nonsteroidal anti-inflammatory drug (NSAID), loxoprofen, completely
      removed the symptoms immediately after the administration. In those cases, since
      the patients were predisposed to atopic disorders, an increased immunological
      response based on the lymphocyte hypersensitivity was likely to be involved in
      the pathogenesis. The immunomodulatory property of NSAID was thought to repress
      such lymphocyte activity and thus provided a rapid and sustained remission of the
      disease.

PMID- 22611410
TI  - Participation in physical activity for children with neurodevelopmental
      disorders.
AB  - The purpose of this study was to compare rates of participation for children (4-9
      years of age) with neurodevelopmental disorders (NDDs) with and without
      externalizing behavior problems (EBPs) with children without disability and to
      examine mediators of the relation between disability and physical activity
      participation. Data for this study were drawn from Cycle 7 (2006-07) of the
      Canadian National Longitudinal Survey of Children and Youth (NLSCY). The
      frequency of children's participation in organized sports or physical activities
      varied depending on the child's health condition with children with NDDs and both
      NDDs and EBPs participating least in organized sports or physical activities
      followed by children with EBPs only. In contrast, there were no statistically
      significant differences by health group for children's participation in
      unorganized sports or physical activities. These differences remained even after
      controlling for the effects of other child and family sociodemographic
      characteristics, except for children with EBPs only. These findings highlight the
      importance of considering children's primary and other existing health conditions
      as well as family sociodemographic characteristics in order to better understand
      the factors that influence participation in organized physical activities for
      children with disabilities.

PMID- 22611411
TI  - Factors influencing physical activity in children and youth with special health
      care needs: a pilot study.
AB  - Background. Evidence suggests that children and youth with special health care
      needs (CYSHCN) have decreased physical activity compared to peers. This study
      describes weight status and physical activity in CYSHCN and identifies factors
      associated with physical activity and community resources to promote physical
      activity. Methods. Parents (n = 21) and CYSHCN (n = 23) were recruited from a
      pediatric clinic. The most prevalent diagnoses were autism (n = 7, 30%) and
      cerebral palsy (n = 3, 13%). Interviews were conducted with parents for
      information on physical activity and community resources. Children's height and
      weight were measured to calculate body mass index (BMI). Results. The majority of
      CYSHCN (n = 13, 59%) were obese. CYSHCN did not meet recommended levels of 60
      minutes of daily physical activity and engaged in more screen time than
      recommended. More children with cognitive/behavioral/emotional diagnoses were
      obese compared to children with physical/medical diagnoses. A majority of parents
      (n = 16, 73%) indicated their CYSHCN need more supervision to participate in
      physical activity in community programs. Conclusion. The majority of CYSHCN in
      this study were obese and sedentary. Resources to promote physical activity are
      needed for this population.

PMID- 22611413
TI  - Postnatal acute famine and risk of overweight: the dutch hungerwinter study.
AB  - Objective. To examine the association between undernutrition during postnatal
      periods of development and the risk of overweight in adulthood. Methods. We
      studied 8,091 women from Prospect-EPIC, exposed to the Dutch famine at ages
      between 0 and 21 years, recruited at ages between 49 and 70 years. We used linear
      and logistic regression models to explore the effect of famine on BMI, waist
      circumference, and the risk of overweight. Results. Overall, postnatal famine
      exposure was associated with increased BMI and waist circumference in a dose
      dependent manner (P  for trend < 0.01). Furthermore, risk of overweight was
      increased following famine exposure (P  for trend = 0.01), with those severely
      exposed at ages 0-9 years having 25% (95% CI 1.05 to 1.50) higher risk compared
      to unexposed women. Conclusions. This study is the first to directly show a
      positive association between short and transient undernutrition during postnatal
      development and BMI, waist circumference, and overweight in adulthood.

PMID- 22611412
TI  - Hemangiomas and vascular malformations: current theory and management.
AB  - Vascular anomalies are a heterogeneous group of congenital blood vessel disorders
      more typically referred to as birthmarks. Subcategorized into vascular tumors and
      malformations, each anomaly is characterized by specific morphology,
      pathophysiology, clinical behavior, and management approach. Hemangiomas are the
      most common vascular tumor. Lymphatic, capillary, venous, and arteriovenous
      malformations make up the majority of vascular malformations. This paper reviews
      current theory and practice in the etiology, diagnosis, and treatment of these
      more common vascular anomalies.

PMID- 22611414
TI  - Diverse Effects of Glutathione and UPF Peptides on Antioxidant Defense System in
      Human Erythroleukemia Cells K562.
AB  - The main goal of the present paper was to examine the influence of the
      replacement of gamma-Glu moiety to alpha-Glu in glutathione and in its
      antioxidative tetrapeptidic analogue UPF1 (Tyr(Me)-gamma-Glu-Cys-Gly), resulting
      in alpha-GSH and UPF17 (Tyr(Me)-Glu-Cys-Gly), on the antioxidative defense system
      in K562 cells. UPF1 and GSH increased while UPF17 and alpha-GSH decreased the
      activity of CuZnSOD in K562 cells, at peptide concentration of 10 MUM by 42% and
      38% or 35% and 24%, respectively. After three-hour incubation, UPF1 increased and
      UPF17 decreased the intracellular level of total GSH. Additionally, it was shown
      that UPF1 is not degraded by gamma-glutamyltranspeptidase, which performs
      glutathione breakdown. These results indicate that effective antioxidative
      character of peptides does not depend only on the reactivity of the thiol group,
      but also of the other functional groups, and on the spatial structure of
      peptides.

PMID- 22611415
TI  - Amyloid Beta Peptide slows down sensory-induced hippocampal oscillations.
AB  - Alzheimer's disease (AD) progresses with a deterioration of hippocampal function
      that is likely induced by amyloid beta (Abeta) oligomers. Hippocampal function is
      strongly dependent on theta rhythm, and disruptions in this rhythm have been
      related to the reduction of cognitive performance in AD. Accordingly, both AD
      patients and AD-transgenic mice show an increase in theta rhythm at rest but a
      reduction in cognitive-induced theta rhythm. We have previously found that
      monomers of the short sequence of Abeta (peptide 25-35) reduce sensory-induced
      theta oscillations. However, considering on the one hand that different Abeta
      sequences differentially affect hippocampal oscillations and on the other hand
      that Abeta oligomers seem to be responsible for the cognitive decline observed in
      AD, here we aimed to explore the effect of Abeta oligomers on sensory-induced
      theta rhythm. Our results show that intracisternal injection of Abeta1-42
      oligomers, which has no significant effect on spontaneous hippocampal activity,
      disrupts the induction of theta rhythm upon sensory stimulation. Instead of
      increasing the power in the theta band, the hippocampus of Abeta-treated animals
      responds to sensory stimulation (tail pinch) with an increase in lower
      frequencies. These findings demonstrate that Abeta alters induced theta rhythm,
      providing an in vivo model to test for therapeutic approaches to overcome Abeta
      induced hippocampal and cognitive dysfunctions.

PMID- 22611416
TI  - Characterization of selective antibacterial peptides by polarity index.
AB  - In the recent decades, antibacterial peptides have occupied a strategic position
      for pharmaceutical drug applications and became subject of intense research
      activities since they are used to strengthen the immune system of all living
      organisms by protecting them from pathogenic bacteria. This work proposes a
      simple and easy statistical/computational method through a peptide polarity index
      measure by which an antibacterial peptide subgroup can be efficiently identified,
      that is, characterized by a high toxicity to bacterial membranes but presents a
      low toxicity to mammal cells. These peptides also have the feature not to adopt
      to an alpha-helicoidal structure in aqueous solution. The double-blind test
      carried out to the whole Antimicrobial Peptide Database (November 2011) showed an
      accuracy of 90% applying the polarity index method for the identification of such
      antibacterial peptide groups.

PMID- 22611417
TI  - Pyrazinamide Effects on Cartilage Type II Collagen Amino Acid Composition.
AB  - Introduction. Current therapeutic regimens with first-line antitubercular agents
      are associated to a high rate of adverse effects which could cause pronounced
      changes in collagen's contents and structure. Investigation of these changes is
      very important for optimization of antitubercular therapy and minimization of
      treatment-caused harm. The aim of present paper was to investigate potential
      effect of pyrazinamide on male rats' cartilage type II collagen amino acid
      composition. Materials and Methods. Wistar albino male rats (160-200 g b.w.) were
      divided into three groups: I-received pyrazinamide per os at a dose of 1000 mg/kg
      b.w./day; II-at a dose of 2000 mg/kg b.w./day, in both groups it was given for 60
      days; III-control. After 60 days of the experiment, rats of the experimental
      (groups I and II) and control groups were sacrificed and the amino acids contents
      of male rat cartilage type II collagens were determined using amino acid
      analyzer. Results and Discussion. The study of pyrazinamide effects (administered
      in different doses) on rat cartilage type II collagen amino acid contents
      demonstrated presence of dose-dependent pyrazinamide-mediated quantitative and
      qualitative changes in these rat extracellular matrix proteins in comparison with
      control.

PMID- 22611418
TI  - Mechanisms behind functional avidity maturation in T cells.
AB  - During an immune response antigen-primed B-cells increase their antigen
      responsiveness by affinity maturation mediated by somatic hypermutation of the
      genes encoding the antigen-specific B-cell receptor (BCR) and by selection of
      higher-affinity B cell clones. Unlike the BCR, the T-cell receptor (TCR) cannot
      undergo affinity maturation. Nevertheless, antigen-primed T cells significantly
      increase their antigen responsiveness compared to antigen-inexperienced (naive) T
      cells in a process called functional avidity maturation. This paper covers
      studies that describe differences in T-cell antigen responsiveness during T-cell
      differentiation along with examples of the mechanisms behind functional avidity
      maturation in T cells.

PMID- 22611419
TI  - Cytokines and HCV-related disorders.
AB  - Cytokines are intercellular mediators involved in viral control and liver damage
      being induced by infection with hepatitis C virus (HCV). The complex cytokine
      network operating during initial infection allows a coordinated, effective
      development of both innate and adaptive immune responses. However, HCV interferes
      with cytokines at various levels and escapes immune response by inducing a T
      helper (Th)2/T cytotoxic 2 cytokine profile. Inability to control infection leads
      to the recruitment of inflammatory infiltrates into the liver parenchyma by
      interferon (IFN)-gamma-inducible CXC chemokine ligand (CXCL)-9, -10, and -11
      chemokines, which results in sustained liver damage and eventually in liver
      cirrhosis. The most important systemic HCV-related extrahepatic diseases--mixed
      cryoglobulinemia, lymphoproliferative disorders, thyroid autoimmune disorders,
      and type 2 diabetes--are associated with a complex dysregulation of the
      cytokine/chemokine network, involving proinflammatory and Th1 chemokines. The
      therapeutical administration of cytokines such as IFN-alpha may result in viral
      clearance during persistent infection and reverts this process.

PMID- 22611420
TI  - Chronic gastritis in dermatitis herpetiformis: a controlled study.
AB  - BACKGROUND AND OBJECTIVE: Previous small studies suggest that chronic atrophic
      gastritis is common in dermatitis herpetiformis (DH). We here examined the
      frequency and topography of chronic gastritis in 93 untreated DH subjects and in
      186 controls with dyspepsia. METHODS: Specimens were drawn from the gastric
      corpus and antrum and examined for atrophy, intestinal metaplasia, and
      Helicobacter pylori. Duodenal biopsies were taken. RESULTS: Atrophic corpus
      gastritis was more frequent in DH than in controls (16.0% and 2.7%, resp., P <
      0.001); atrophy in the antrum was rare in both groups (3.2% and 1.1%, P = 0.34).
      Intestinal metaplasia was present in 13 (14.0%) DH and 12 (6.5%) control patients
      (P = 0.038) and H. pylori in 17 (18.3%) and 17 (9.3%) (P = 0.028), respectively.
      Small-bowel villous atrophy was seen in 76% of the DH patients, equally in
      patients with and without chronic gastritis. One DH patient with atrophic
      gastritis developed gastric cancer. CONCLUSION: In DH, chronic atrophic gastritis
      was common in the corpus, but not in the antrum. H. pylori will partly explain
      this, but corpus atrophy is suggestive of an autoimmune etiology. Atrophic
      gastritis may increase the risk of gastric cancer. We advocate performing upper
      endoscopy with sufficient histologic samples in DH.

PMID- 22611421
TI  - Programmed death ligand 2 in cancer-induced immune suppression.
AB  - Inhibitory molecules of the B7/CD28 family play a key role in the induction of
      immune tolerance in the tumor microenvironment. The programmed death-1 receptor
      (PD-1), with its ligands PD-L1 and PD-L2, constitutes an important member of
      these inhibitory pathways. The relevance of the PD-1/PD-L1 pathway in cancer has
      been extensively studied and therapeutic approaches targeting PD-1 and PD-L1 have
      been developed and are undergoing human clinical testing. However, PD-L2 has not
      received as much attention and its role in modulating tumor immunity is less
      clear. Here, we review the literature on the immunobiology of PD-L2, particularly
      on its possible roles in cancer-induced immune suppression and we discuss the
      results of recent studies targeting PD-L2 in cancer.

PMID- 22611422
TI  - Immunogenic targets for specific immunotherapy in multiple myeloma.
AB  - Multiple myeloma remains an incurable disease although the prognosis has been
      improved by novel therapeutics and agents recently. Relapse occurs in the
      majority of patients and becomes fatal finally. Immunotherapy might be a powerful
      intervention to maintain a long-lasting control of minimal residual disease or to
      even eradicate disseminated tumor cells. Several tumor-associated antigens have
      been identified in patients with multiple myeloma. These antigens are expressed
      in a tumor-specific or tumor-restricted pattern, are able to elicit immune
      response, and thus could serve as targets for immunotherapy. This review
      discusses immunogenic antigens with therapeutic potential for multiple myeloma.

PMID- 22611423
TI  - Nonprotein structures from mycobacteria: emerging actors for tuberculosis
      control.
AB  - Immune response to Mycobacterium tuberculosis, the causal agent of tuberculosis,
      is critical for protection. For many decades, consistent to classical
      biochemistry, most studies regarding immunity to the tubercle bacilli focused
      mainly on protein structures. But the atypical, highly impermeable and waxy coat
      of mycobacteria captured the interest of structural biologists very early,
      allowing the description of amazing molecules, such as previously unknown
      carbohydrates or fatty acids of astonishing lengths. From their discovery, cell
      wall components were identified as important structural pillars, but also as
      molecular motifs able to alter the human immune response. Recently, as new
      developments have emerged, classical conceptions of mycobacterial immune
      modulators have been giving place to unexpected discoveries that, at the turn of
      the last century, completely changed our perception of immunity vis-a-vis fat
      compounds. In this paper, current knowledge about chemical and ultrastructural
      features of mycobacterial cell-wall is overviewed, with an emphasis on the
      relationships between cell-wall nonpeptide molecules and immune response. Remarks
      regarding the potential of these molecules for the development of new tools
      against tuberculosis are finally discussed.

PMID- 22611424
TI  - Modulation of gastrointestinal inflammation and colorectal tumorigenesis by
      peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta).
AB  - Critical physiological roles of peroxisome proliferator-activated receptor
      beta/delta (PPARbeta/delta) include the regulation glucose and lipid homeostasis,
      cellular differentiation, and modulation of inflammation. The potential for
      targeting PPARbeta/delta for the prevention and treatment of metabolic diseases
      or cancer, is compromised because of major inconsistencies in the literature.
      This is due primarily to uncertainty regarding the effect of PPARbeta/delta and
      its activation on cell proliferation, apoptosis and cell survival. This review
      summarizes both the confirmed and conflicting mechanisms that have been described
      for PPARbeta/delta and the potential for targeting this nuclear receptor for the
      prevention and treatment of colon cancer.

PMID- 22611425
TI  - Electroacupuncture Pretreatment as a Novel Avenue to Protect Brain against
      Ischemia and Reperfusion Injury.
AB  - Electroacupuncture (EA) pretreatment is a recent observation which has been shown
      to induce ischemic tolerance mimicking the ischemic pretreatment, suggesting that
      EA pretreatment may be a promising preventive strategy for the patients with high
      risk of acute ischemia/reperfusion injury. It was first described in the brain,
      then in the heart where EA stimulation at acupoint prior to ischemia led to
      neuroprotection and myocardial protection and induced rapid and delayed ischemic
      tolerance. Then the optimal parameters and acupoint specificity of EA
      pretreatment to induce protective effect were proved. Many studies have shown
      that protective mechanisms of EA pretreatment may involve a series of regulatory
      molecular pathways including activity enhancement of antioxidant, regulation of
      the endocannabinoid system, involvement of beta-adrenergic receptor, and
      postreceptor signaling pathway, inhibition of apoptosis. Recently, the
      neuroprotective and cardioprotective effect of EA pretreatment had been
      demonstrated in patients undergoing craniocerebral tumor resection or heart valve
      replacement surgery. Thus, the purpose of this paper is to collect the evidence
      for the neuroprotective effect of EA pretreatment, to summarize the proposed
      protective mechanisms of EA pretreatment, and to discuss the possibility of EA
      pretreatment as a new preventive strategy for patients with high risk of ischemia
      in clinic.

PMID- 22611426
TI  - Solanum lyratum Extracts Induce Extrinsic and Intrinsic Pathways of Apoptosis in
      WEHI-3 Murine Leukemia Cells and Inhibit Allograft Tumor.
AB  - We investigated the molecular mechanisms of cell cycle arrest and apoptotic death
      induced by Solanum lyratum extracts (SLE) or diosgenin in WEHI-3 murine leukemia
      cells in vitro and antitumor activity in vivo. Diosgenin is one of the components
      of SLE. Our study showed that SLE and diosgenin decreased the viable WEHI-3 cells
      and induced G(0)/G(1) phase arrest and apoptosis in concentration- or time
      dependent manners. Both reagents increased the levels of ROS production and
      decreased the mitochondrial membrane potential (DeltaPsi(m)). SLE- and diosgenin
      triggered apoptosis is mediated through modulating the extrinsic and intrinsic
      signaling pathways. Intriguingly, the p53 inhibitor (pifithrin-alpha), anti-Fas
      ligand (FasL) mAb, and specific inhibitors of caspase-8 (z-IETD-fmk), caspase-9
      (z-LEHD-fmk), and caspase-3 (z-DEVD-fmk) blocked SLE- and diosgenin-reduced cell
      viability of WEHI-3 cells. The in vivo study demonstrated that SLE has marked
      antitumor efficacy against tumors in the WEHI-3 cell allograft model. In
      conclusion, SLE- and diosgenin-induced G(0)/G(1) phase arrest and triggered
      extrinsic and intrinsic apoptotic pathways via p53 activation in WEHI-3 cells.
      SLE also exhibited antitumor activity in vivo. Our findings showed that SLE may
      be potentially efficacious in the treatment of leukemia in the future.

PMID- 22611427
TI  - Quality of life and functional health status of long-term meditators.
AB  - Background. There is very little data describing the long-term health impacts of
      meditation. Aim. To compare the quality of life and functional health of long
      term meditators to that of the normative population in Australia. Method. Using
      the SF-36 questionnaire and a Meditation Lifestyle Survey, we sampled 343 long
      term Australian Sahaja Yoga meditation practitioners and compared their scores to
      those of the normative Australian population. Results. Six SF-36 subscales
      (bodily pain, general health, mental health, role limitation-emotional, social
      functioning, and vitality) were significantly better in meditators compared to
      the national norms whereas two of the subscales (role limitation-physical,
      physical functioning) were not significantly different. A substantial correlation
      between frequency of mental silence experience and the vitality, general health,
      and especially mental health subscales (P < 0.005) was found. Conclusion. Long
      term practitioners of Sahaja yoga meditation experience better functional health,
      especially mental health, compared to the general population. A relationship
      between functional health, especially mental health, and the frequency of
      meditative experience (mental silence) exists that may be causal. Evidence for
      the potential role of this definition of meditation in enhancing quality of life,
      functional health and wellbeing is growing. Implications for primary mental
      health prevention are discussed.

PMID- 22611428
TI  - The Relationship between Plants Used to Sustain Finches (Fringillidae) and Uses
      for Human Medicine in Southeast Spain.
AB  - We analyzed plants that are traditionally used by wild bird hunters and breeders
      to capture and promote captive breeding of Fringillidae (finches or songbirds) in
      the province of Alicante, Spain. The majority of plants used in songbird breeding
      have medicinal properties in traditional human medicine (48 different uses);
      thus, another main goal was to show their relationships with human medical uses.
      We compiled a list of 97 plant species from 31 botanical families that are used
      to attract finches and identified 11 different use categories for these plants in
      finch keeping. The most common uses were for trapping birds and as a source of
      food for birds in captivity. Cannabis sativa has the greatest cultural importance
      index (CI = 1.158), and Phalaris canariensis (annual canary grass or alpist) was
      the most common species used to attract Fringillidae and was used by all
      informants (n = 158). Most of the 97 species are wild plants and mainly belong to
      the families Compositae, Gramineae, Cruciferae, and Rosaceae and also have
      medicinal properties for humans. In the study area, the intensification of
      agriculture and abandonment of traditional management practices have caused the
      population of many songbirds to decline, as well as the loss of popular
      ethnographic knowledge.

PMID- 22611429
TI  - Melanogenesis and antityrosinase activity of selected South african plants.
AB  - Melanin is the pigment that is responsible for the colour of eyes, hair, and skin
      in humans. Tyrosinase is known to be the key enzyme in melanin biosynthesis.
      Overactivity of this enzyme leads to dermatological disorders such as age spots,
      melanoma and sites of actinic damage. Ten plants belonging to four families
      (Asphodelaceae, Anacardiaceae, Oleaceae, and Rutaceae) were investigated for
      their effect on tyrosinase using both L-tyrosine and L-DOPA as substrates.
      Ethanol leaf extracts (500 MUg/mL) of Aloe ferox, Aloe aculeata, Aloe
      pretoriensis, and Aloe sessiliflora showed 60%, 31%, 17%, and 13% inhibition of
      tyrosinase activity respectively, when L-tyrosine was used as a substrate.
      Harpephyllum caffrum (leaves) at a concentration of 500 MUg/mL had an inhibitory
      effect of 70% on tyrosinase when L-DOPA was used as a substrate. The IC(50) of
      Harpephyllum caffrum (leaves and bark) were found to be 51 +/- 0.002 and 40 +/-
      0.035 MUg/mL, respectively. Following the results obtained from the tyrosinase
      assay, extracts from Harpephyllum caffrum were selected for further testing on
      their effect on melanin production and their cytotoxicity on melanocytes in
      vitro. The IC(50) of both extracts was found to be 6.25 MUg/mL for melanocyte
      cells. Bark extract of Harpephyllum caffrum showed 26% reduction in melanin
      content of melanocyte cells at a concentration of 6.25 MUg/mL. The leaf extract
      of this plant showed some toxicity on melanocyte cells. Therefore, the bark
      extract of Harpephyllum caffrum could be considered as an antityrosinase agent
      for dermatological disorders such as age spots and melasoma.

PMID- 22611430
TI  - Chinese medicine shenfu injection for heart failure: a systematic review and meta
      analysis.
AB  - Objective. Heart failure (HF) is a global public health problem. Early literature
      studies manifested that Shenfu injection (SFI) is one of the most commonly used
      traditional Chinese patent medicine for HF in China. This article intended to
      systematically evaluate the efficacy and safety of SFI for HF. Methods. An
      extensive search was performed within 6 English and Chinese electronic database
      up to November 2011. Ninety-nine randomized controlled trails (RCTs) were
      collected, irrespective of languages. Two authors extracted data and assessed the
      trial quality independently. RevMan 5.0.2 was used for data analysis. Results.
      Compared with routine treatment and/or device support, SFI combined with routine
      treatment and/or device support showed better effect on clinical effect rate,
      mortality, heart rate, NT-proBNP and 6-minute walk distance. Results in
      ultrasonic cardiography also showed that SFI combined with routine treatment
      improved heart function of HF patients. There were no significant difference in
      blood pressure between SFI and routine treatment groups. Adverse events were
      reported in thirteen trails with thirteen specific symptoms, while no serious
      adverse effect was reported. Conclusion. SFI appear to be effective for treating
      HF. However, further rigorously designed RCTs are warranted because of
      insufficient methodological rigor in the majority of included trials.

PMID- 22611431
TI  - Transcutaneous Electrical Nerve Stimulation on the PC-5 and PC-6 Points
      Alleviated Hypotension after Epidural Anaesthesia, Depending on the Stimulus
      Frequency.
AB  - Neuraxial blockade causes arterial hypotension. Transcutaneous electrical nerve
      stimulation (TENS) at the Neiguan (PC-6) and Jianshi (PC-5) reduces the severity
      of hypotension after spinal anaesthesia, but did not clarify the optimal stimulus
      frequency. We hypothesized that the stimulus frequency of TENS at the PC-6 and PC
      5 points would influence the severity of hypotension after epidural anaesthesia.
      65 ASA I or II male patients presenting for inguinal hernia repair were
      randomized to five groups: the control group received no treatment; the 2 Hz, 10
      Hz, 20 Hz, and 40 Hz groups received TENS at a frequency of 2 Hz, 10 Hz, 20 Hz,
      and 40 Hz, respectively. The lowest SBP was significantly higher in the 40 Hz
      group [the control, 84 (74-110) mmHg; the 2 Hz, 96 (62-116) mmHg; the 10 Hz, 100
      (68-110) mmHg; the 20 Hz, 96 (64-115) mmHg; the 40 Hz, 104 (75-140) mmHg: P =
      0.004]. Significantly less patients experienced hypotension in the 40 Hz group
      [the control, 78%; the 2 Hz, 43%; the 10 Hz, 38%; the 20 Hz, 38%; the 40 Hz, 8%:
      P = 0.008]. TENS on the PC-6 and PC-5 points reduced the severity and incidence
      of hypotension after epidural anaesthesia, depending on the stimulus frequency.

PMID- 22611432
TI  - Influence of fructooligosaccharide on pharmacokinetics of isoflavones in
      postmenopausal women.
AB  - The objective of the present paper was to determine the influence of
      fructooligosaccharide (FOS) on the pharmacokinetics of isoflavones in healthy
      postmenopausal women. The study was a fixed-sequence, two-phase, crossover study.
      Twelve subjects received a single oral dose of 300 mL of a soy beverage. Blood
      samples were collected before the dose and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, and
      32 h after the administration of the soy beverage. After a washout period of at
      least 1 week, subjects were assigned to receive oral doses of FOS, 5 g each time,
      twice a day (after breakfast and dinner) for 14 days, followed by a single oral
      dose of the same soy beverage on the next day. Blood samples were then collected
      at the same time points mentioned previously. Plasma isoflavone concentrations
      were determined by HPLC. Continuous oral administrations of FOS followed by a
      single oral administration of soy beverage caused significant increases in
      C(max), AUC(0-32), and AUC(0-infinity) of genistein and AUC(0-32) of daidzein,
      comparing to those obtained following a single oral dose of soy beverage alone.
      Other pharmacokinetic parameters (T(max) and t(1/2) of both aglycones and AUC(0
      infinity) of daidzein) between both regimens were not significantly different.

PMID- 22611433
TI  - Synergistic Antimycobacterial Actions of Knowltonia vesicatoria (L.f) Sims.
AB  - Euclea natalensis A.DC., Knowltonia vesicatoria (L.f) Sims, and Pelargonium
      sidoides DC. are South African plants traditionally used to treat tuberculosis.
      Extracts from these plants were used in combination with isoniazid (INH) to
      investigate the possibility of synergy with respect to antimycobacterial
      activity. The ethanol extract of K. vesicatoria was subjected to fractionation to
      identify the active compounds. The activity of the Knowltonia extract remained
      superior to the fractions with a minimum inhibitory concentration (MIC) of 625.0
      MUg/mL against Mycobacterium smegmatis and an MIC of 50.00 MUg/mL against M.
      tuberculosis. The K. vesicatoria extract was tested against two different drug
      resistant strains of M. tuberculosis, which resulted in an MIC of 50.00 MUg/mL on
      both strains. The combination of K. vesicatoria with INH exhibited the best
      synergistic antimycobacterial activity with a fractional inhibitory concentration
      index of 0.25 (a combined concentration of 6.28 MUg/mL). A fifty percent
      inhibitory concentration of this combination against U937 cells was 121.0 MUg/mL.
      Two compounds, stigmasta-5,23-dien-3-ol (1) and 5-(hydroxymethyl)furan-2(5H)-one
      (2), were isolated from K. vesicatoria as the first report of isolation for both
      compounds from this plant and the first report of antimycobacterial activity.
      Compound (1) was active against drug-sensitive M. tuberculosis with an MIC of
      50.00 MUg/mL.

PMID- 22611434
TI  - The Effects of Velvet Antler of Deer on Cardiac Functions of Rats with Heart
      Failure following Myocardial Infarction.
AB  - Velvet antler of deer (VAD) is a commonly-used kidney-Yang supplementing
      traditional Chinese medication. According to the heart-kidney-related theory,
      heart Yang originates in kidney Yang and heart failure due to heart Yang
      deficiency can be treated by tonifying kidney Yang. In this study, we
      investigated therapeutic effects of VAD on cardiac functions in rats with heart
      failure following myocardial infarction. Forty-eight male Wistar rats were
      subjected either to left coronary artery ligation (N = 36) or to sham operation
      (N = 12). One week after the surgery, rats with heart failure received daily
      treatment of double-distilled water, captopril or VAD by gavage for consecutively
      four weeks, while sham-operated animals were given double-distilled water.
      Ultrasonic echocardiography was adopted to examine cardiac structural and
      functional parameters and serum brain natriuretic peptide (BNP) concentration was
      measured using radioimmunoassay. We found that VAD partially reversed changes in
      cardiac functional parameters and serum BNP levels in rats with heart failure.
      These results provide further evidence for the heart-kidney-related theory and
      suggest that VAD might be a potentially alternative and complementary medicine
      for the treatment of heart failure.

PMID- 22611435
TI  - Regulation of Proinflammatory Mediators via NF-kappaB and p38 MAPK-Dependent
      Mechanisms in RAW 264.7 Macrophages by Polyphenol Components Isolated from Korea
      Lonicera japonica THUNB.
AB  - Lonicera japonica THUNB., which abundantly contains polyphenols, has been used as
      a traditional medicine for thousands of years in East Asian countries because of
      the anti-inflammation properties. This study aimed to investigate the anti
      inflammatory mechanism of polyphenol components isolated from Korea L. japonica
      T. by nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein kinases
      (MAPKs) pathway. Polyphenols significantly decreased lipopolysaccharide- (LPS-)
      induced mRNA and protein expression of inducible nitric oxide synthase and
      cyclooxygenase-2, as well as mRNA expression of tumor necrosis factor-alpha,
      interleukin- (IL-) 1beta, and IL-6. Moreover, polyphenols inhibited nuclear
      translocation of NF-kappaB p65, phosphorylation/degradation of the inhibitor of
      kappaB, and phosphorylation of p38 MAPK, whereas the extracellular signal
      regulated kinase and Janus N-terminal kinase were not affected. These results
      indicate that polyphenol components isolated from Korea L. japonica T. should
      have anti-inflammatory effect on LPS-stimulated RAW 264.7 cells through the
      decrease of proinflammatory mediators expression by suppressing NF-kappaB and p38
      MAPK activity.

PMID- 22611436
TI  - Xanthohumol, a Prenylated Flavonoid from Hops (Humulus lupulus), Prevents
      Platelet Activation in Human Platelets.
AB  - Xanthohumol is the principal prenylated flavonoid in the hop plant (Humulus
      lupulus L.). Xanthohumol was found to be a very potent cancer chemopreventive
      agent through regulation of diverse mechanisms. However, no data are available
      concerning the effects of xanthohumol on platelet activation. The aim of this
      paper was to examine the antiplatelet effect of xanthohumol in washed human
      platelets. In the present paper, xanthohumol exhibited more-potent activity in
      inhibiting platelet aggregation stimulated by collagen. Xanthohumol inhibited
      platelet activation accompanied by relative [Ca(2+)](i) mobilization, thromboxane
      A(2) formation, hydroxyl radical (OH(?)) formation, and phospholipase C
      (PLC)gamma2, protein kinase C (PKC), mitogen-activated protein kinase (MAPK), and
      Akt phosphorylation. Neither SQ22536, an inhibitor of adenylate cyclase, nor ODQ,
      an inhibitor of guanylate cyclase, reversed the xanthohumol-mediated inhibitory
      effect on platelet aggregation. Furthermore, xanthohumol did not significantly
      increase nitrate formation in platelets. This study demonstrates for the first
      time that xanthohumol possesses potent antiplatelet activity which may initially
      inhibit the PI3-kinase/Akt, p38 MAPK, and PLCgamma2-PKC cascades, followed by
      inhibition of the thromboxane A(2) formation, thereby leading to inhibition of
      [Ca(2+)](i) and finally inhibition of platelet aggregation. Therefore, this novel
      role of xanthohumol may represent a high therapeutic potential for treatment or
      prevention of cardiovascular diseases.

PMID- 22611437
TI  - Antinociceptive Activity of Methanol Extract of Muntingia calabura Leaves and the
      Mechanisms of Action Involved.
AB  - Muntingia calabura L. (family Elaeocarpaceae) has been traditionally used to
      relieve various pain-related ailments. The present study aimed to determine the
      antinociceptive activity of methanol extract of M. calabura leaves (MEMC) and to
      elucidate the possible mechanism of antinociception involved. The in vivo
      chemicals (acetic acid-induced abdominal constriction and formalin-, capsaicin-,
      glutamate-, serotonin-induced paw licking test) and thermal (hot plate test)
      models of nociception were used to evaluate the extract antinociceptive activity.
      The extract (100, 250, and 500 mg/kg) was administered orally 60 min prior to
      subjection to the respective test. The results obtained demonstrated that MEMC
      produced significant (P < 0.05) antinociceptive response in all the chemical- and
      thermal-induced nociception models, which was reversed after pretreatment with 5
      mg/kg naloxone, a non-selective opioid antagonist. Furthermore, pretreatment with
      L-arginine (a nitric oxide (NO) donor), N(G)-nitro-L-arginine methyl esters (L
      NAME; an inhibitor of NO synthase (NOS)), methylene blue (MB; an inhibitor of
      cyclic-guanosine monophosphate (cGMP) pathway), or their combination also caused
      significant (P < 0.05) change in the intensity of the MEMC antinociception. In
      conclusion, the MEMC antinociceptive activity involves activation of the
      peripheral and central mechanisms, and modulation via, partly, the opioid
      receptors and NO/cGMP pathway.

PMID- 22611439
TI  - Source activity correlation effects on LCMV beamformers in a realistic
      measurement environment.
AB  - In EEG and MEG studies on brain functional connectivity and source interactions
      can be performed at sensor or source level. Beamformers are well-established
      source-localization tools for MEG/EEG signals, being employed in source
      connectivity studies both in time and frequency domain. However, it has been
      demonstrated that beamformers suffer from a localization bias due to correlation
      between source time courses. This phenomenon has been ascertained by means of
      theoretical proofs and simulations. Nonetheless, the impact of correlated sources
      on localization outputs with real data has been disputed for a long time. In this
      paper, by means of a phantom, we address the correlation issue in a realistic MEG
      environment. Localization performances in the presence of simultaneously active
      sources are studied as a function of correlation degree and distance between
      sources. A linear constrained minimum variance (LCMV) beamformer is applied to
      the oscillating signals generated by the current dipoles within the phantom.
      Results show that high correlation affects mostly dipoles placed at small
      distances (1, 5 centimeters). In this case the sources merge. If the dipoles lie
      3 centimeters apart, the beamformer localization detects attenuated power
      amplitudes and blurred sources as the correlation level raises.

PMID- 22611438
TI  - Lipid-regulating effect of traditional chinese medicine: mechanisms of actions.
AB  - Traditional Chinese medicine (TCM) has been increasingly used for the treatment
      of dyslipidemia and cardiovascular disease. Recently, much progress has been made
      in studies on the mechanisms of action of the lipid-regulating effect of TCM in
      animal experiments. Current researches showed that the lipid-regulating effect of
      TCM may be related to the following actions: (1) inhibiting intestinal absorption
      of lipids; (2) reducing the biosynthesis of endogenous lipids; (3) increasing the
      catabolism of lipid, sterol substances in live system; (4) increasing the
      secretion of sterol substances in live system; (5) regulating transcription
      factors related to lipid metabolism. This paper provides an overview of the
      recent advances and discusses their implications in future development of lipid
      lowering drugs from TCM.

PMID- 22611440
TI  - Theorems and application of local activity of CNN with five state variables and
      one port.
AB  - Coupled nonlinear dynamical systems have been widely studied recently. However,
      the dynamical properties of these systems are difficult to deal with. The local
      activity of cellular neural network (CNN) has provided a powerful tool for
      studying the emergence of complex patterns in a homogeneous lattice, which is
      composed of coupled cells. In this paper, the analytical criteria for the local
      activity in reaction-diffusion CNN with five state variables and one port are
      presented, which consists of four theorems, including a serial of inequalities
      involving CNN parameters. These theorems can be used for calculating the
      bifurcation diagram to determine or analyze the emergence of complex dynamic
      patterns, such as chaos. As a case study, a reaction-diffusion CNN of hepatitis B
      Virus (HBV) mutation-selection model is analyzed and simulated, the bifurcation
      diagram is calculated. Using the diagram, numerical simulations of this CNN model
      provide reasonable explanations of complex mutant phenomena during therapy.
      Therefore, it is demonstrated that the local activity of CNN provides a practical
      tool for the complex dynamics study of some coupled nonlinear systems.

PMID- 22611441
TI  - Update on diagnosis, pathogenesis and management of ketosis-prone Type 2 diabetes
      mellitus.
AB  - Diabetic ketoacidosis (DKA) has been considered a key clinical feature of Type 1
      diabetes mellitus; however, increasing evidence indicates that DKA is also a
      common feature of Type 2 diabetes (T2DM). Many cases of DKA develop under
      stressful conditions such as trauma or infection but an increasing number of
      cases without precipitating cause have been reported in children and adults with
      T2DM. Such patients present with severe hyperglycemia and ketosis as in Type 1
      diabetes mellitus but can discontinue insulin after a few months and maintain
      acceptable glycemic control on diet or oral agents. This subtype of diabetes has
      been referred to as ketosis-prone T2DM. In this article, we reviewed the
      literature on ketosis-prone T2DM and summarized the epidemiology, putative
      pathophysiology and approaches to management.

PMID- 22611442
TI  - Results of the femur fractures treated with the new selfdynamisable internal
      fixator (SIF).
AB  - PURPOSE: As axial dynamisation is a recognised method, many authors using
      interlocking femoral nail perform an additional small operation two months after
      the primary operation in order to remove one screw so as to provide axial
      dynamisation. According to the literature, dynamisation happens in about 15-25%
      of cases, but it cannot be predicted which patient or fracture will need
      dynamisation. The aim of this study is to present a new selfdynamisable implant
      and a minimally invasive method for the internal fixation of different femoral
      fractures. MATERIALS AND METHODS: The study was conducted between 2000 and 2008
      and included 849 patients with 871 fractures receiving the selfdynamisable
      internal fixator (SIF) for proximal, diaphyseal and distal femur fractures.
      RESULTS: The average operative time was 44 min (23-119 min) and the average
      fluoroscopy time was 12 s (6-92 s), while the average blood loss was 90 ml (60
      250 ml) when a minimally invasive technique was used. None of the patients
      developed complications during the intra-operative period. Complete follow-up was
      available in 726 patients with 738 fractures. The healing time was 3.9 months (3
      9 months). Healing was achieved in 99.1% of patients. Superficial infection
      developed in seven fixations (0.9%), while deep infection developed in four
      patients (0.5%). Screw-breaking occurred within 6-18 weeks in 19 fixations
      (2.6%). Cut-out phenomenon happened in 24 cases. Spontaneous axial dynamisation
      was observed in 71 (23.8%) out of 738 fractures, being 5 mm on average (2-12 mm).
      CONCLUSION: The SIF is an effective method for the treatment of femoral
      fractures. This method is particularly valuable in the treatment of comminuted
      fractures with regard to minimally invasive surgery. ELECTRONIC SUPPLEMENTARY
      MATERIAL: The online version of this article (doi:10.1007/s00068-011-0157-7)
      contains supplementary material, which is available to authorized users.

PMID- 22611443
TI  - Trends in cardiovascular risk factors among patients with coronary heart disease:
      results from the EUROASPIRE I, II, and III surveys in the Munster region.
AB  - BACKGROUND: Target values for cardiovascular risk factors in patients with
      coronary heart disease (CHD) are stated in guidelines for the prevention of
      cardiovascular disease. We studied secular trends in risk factors over a 12-year
      period among CHD patients in the region of Munster, Germany. METHODS: The cross
      sectional EUROASPIRE I, II and III surveys were performed in multiple centers
      across Europe. For all three, the Munster region was the participating German
      region. In the three periods 1995/96, 1999/2000, and 2006/07, the surveys
      included (respectively) 392, 402 and 457 <= 70-year-old patients with CHD in
      Munster who had sustained a coronary event at least 6 months earlier. RESULTS:
      The prevalence of smoking remained unchanged, with 16.8% in EUROASPIRE I and II
      and 18.4% in EUROASPIRE III (p=0.898). On the other hand, high blood pressure and
      high cholesterol both became less common across the three EUROASPIRE studies
      (60.7% to 69.4% to 55.3%, and 94.3% to 83.4% to 48.1%, respectively; p<0.001 for
      both). Obesity became more common (23.0% to 30.6% to 43.1%, p<0.001), as did
      treatment with antihypertensive and lipid-lowering drugs (80.4% to 88.6% to
      94.3%, and 35.0% to 67.4% to 87.0%, respectively; p<0.001 for both). CONCLUSION:
      The observed trends in cardiovascular risk factors under-score the vital need for
      better preventive strategies in patients with CHD.

PMID- 22611444
TI  - A pseudo-quality assurance fig leaf.

PMID- 22611445
TI  - Anxiety as an important factor.

PMID- 22611446
TI  - An experimental procedure paid for by the general public.

PMID- 22611447
TI  - Stress: aspects of endocrine hypertension.

PMID- 22611448
TI  - Biased reasoning.

PMID- 22611449
TI  - A new procedure, but for whom?

PMID- 22611451
TI  - Ejaculate in differential diagnosis.

PMID- 22611453
TI  - The treatment of climacteric symptoms.
AB  - BACKGROUND: Peri- and postmenopausal women commonly suffer from climacteric
      symptoms. In this article, we provide information to help physicians recognize
      climacteric symptoms and treat them appropriately. METHODS: The information
      presented here is based on a selective search of the literature for pertinent
      articles that appeared from 2008 to early 2011, including the German S3 guideline
      on hormone therapy (HT) during and after menopause, which was published in 2009.
      RESULTS: Perimenopausal women often suffer from climacteric symptoms. Typically,
      women undergoing menopause complain of heat waves and vaginal dryness. According
      to randomized controlled trials as well as national and international guidelines,
      HT is the most effective treatment for vasomotor symptoms and also improves
      vulvovaginal atrophy; for the latter indication, HT is preferably administered
      locally. Vaginal estrogen therapy lowers the frequency of recurrent urinary tract
      infections. However, HT is associated with an increased risk for a number of
      diseases, including stroke, thromboembolic events, gall-bladder diseases, and
      breast cancer. Alternative treatments for climacteric symptoms have little or no
      efficacy. CONCLUSION: HT should only be used to treat climacteric symptoms after
      extensive patient education about its benefits and risks. Participatory decision
      making is desirable. The generalized use of HT by all women with climacteric
      symptoms cannot be recommended.

PMID- 22611454
TI  - Antagonistic Action of Lactobacilli and Bifidobacteria in Relation to
      Staphylococcus aureus and Their Influence on the Immune Response in Cases of
      Intravaginal Staphylococcosis in Mice.
AB  - The antibacterial activity of Lactobacillus casei IMV B-7280, Lact. acidophilus
      IMV B-7279, Bifidobacterium longum VK1, and B. bifidum VK2 strains or their
      various compositions in relation to Staphylococcus aureus in vitro and on models
      of experimental intravaginal staphylococcosis of mice was determined. It was
      found that under the influence of these strains and their various compositions,
      the in vitro growth of Staph. aureus was inhibited, and the number of colonies of
      Staph. aureus plated from the vagina of infected mice was significantly reduced.
      The antibacterial activity of these strains separately and in compositions
      correlated with their ability to improve the performance of the immune response.
      These strains were the most effective in the following compositions: Lact. casei
      IMV B-7280-B. longum VK1-B. bifidum VK2. Strains of Lact. casei IMV B-7280, Lact.
      acidophilus IMV B-7279, B. bifidum VK2, and B. longum VK1 are prospective
      components of future probiotic drugs efficient in treating staphylococcosis and
      for immunity correction. 

PMID- 22611455
TI  - Cadmium and lead accumulate in the deciduous teeth of children with celiac
      disease or food allergies.

PMID- 22611456
TI  - Current trends in the surgical management of Dupuytren's disease in Europe: the
      surgeon's perspective.
AB  - INTRODUCTION: Dupuytren's disease (DD), commonly affecting European men, is
      generally treated with surgery.  METHODS: Orthopaedic and plastic surgeons who
      had been practicing for >3 and <30 years and operated on >=5 patients with DD
      between September and December 2008 were surveyed in 12 European countries (Czech
      Republic, Denmark, Finland, France, Germany, Hungary, Italy, The Netherlands,
      Poland, Spain, Sweden and UK). The survey assessed procedures performed, factors
      influencing choice of procedure, use of physical therapy and recurrence.
      Descriptive statistics are reported.  RESULTS: A total of 687 surgeons
      participated, including 579 orthopaedic and 108 plastic surgeons; 383 (56%) were
      hand surgeons. About 37% of surgeons performed percutaneous needle fasciotomy
      (PNF), 77% fasciotomy, 95% fasciectomy and 40% dermofasciectomy (DF). Surgeons'
      choice of procedure was influenced by patient preferences, age, degree of
      contracture and recurrent disease. The percentage of surgeons prescribing
      physical therapy and the mean (standard deviation [SD]) duration of therapy
      increased with procedure complexity: PNF = 82%, 5.2 (3.9) weeks; fasciotomy =
      94%, 5.3 (3.6); fasciectomy = 97%, 6.7 (5.1); and DF = 99%, 8.5 (6.4). Using
      survey responses, mean (SD) estimated recurrence rates decreased and estimated
      time to recurrence increased with procedure complexity-PNF = 44% (27%), 17 (15)
      months; fasciotomy = 30% (24%), 20 (18); fasciectomy = 20% (17%), 29 (23); and DF
      = 20% (19%), 33 (27).  CONCLUSIONS: Across Europe, patient and surgical factors
      influence the intention to use a surgical procedure. Fasciectomy was the most
      commonly performed procedure type and was associated with lower recurrence than
      PNF or fasciotomy.  ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this
      article (doi:10.1007/s12570-012-0091-0) contains supplementary material, which is
      available to authorized users.

PMID- 22611457
TI  - Current trends in the surgical management of Dupuytren's disease in Europe: an
      analysis of patient charts.
AB  - INTRODUCTION: Dupuytren's disease (DD) causes progressive digital flexion
      contracture and is more common in men of European descent.  METHODS: Orthopaedic
      and plastic surgeons in 12 European countries (the Czech Republic, Denmark,
      Finland, France, Germany, Hungary, Italy, The Netherlands, Poland, Spain, Sweden
      and the UK) with >3 and <30 years experience reviewed the medical charts of five
      consecutive patients they had treated surgically for DD in 2008. Descriptive
      statistics are reported.  RESULTS: In total, 3,357 patient charts were reviewed.
      Mean (standard deviation) patient age was 61.9 (10.2) years; 81% were men. At the
      time of the procedure, 11% of patients were at Tubiana stage Ia (0-20 degrees 
      total flexion); 30%, stage Ib (21-45 degrees ); 34%, stage II (46-90 degrees );
      17%, stage III (91-135 degrees ); and 5%, stage IV (>135 degrees ). Percutaneous
      needle fasciotomy was performed in 10%, fasciotomy in 13%, fasciectomy in 69% and
      dermofasciectomy (DF) in 6% of patients. After surgery, fingers improved a mean
      of 1.9 Tubiana stages, and 54% of patients had no nodules or contracture. The
      rate of reported complications during the procedure was 4% overall (11% in
      patients undergoing DF). The most common postoperative complications reported
      were haematoma (8%), wound healing complications (6%) and pain (6%). No
      postoperative complications were reported in 77% of patients.  CONCLUSIONS: In
      this European study of more than 3,000 patients with DD, most patients were
      diagnosed at Tubiana stage I or II, the majority received fasciectomy and more
      than half had no nodules or contracture remaining after surgery.  ELECTRONIC
      SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12570
      012-0092-z) contains supplementary material, which is available to authorized
      users.

PMID- 22611458
TI  - Do new Ethical Issues Arise at Each Stage of Nanotechnological Development?
AB  - The literature concerning ethical issues associated with nanotechnologies has
      become prolific. However, it has been claimed that ethical problems are only at
      stake with rather sophisticated nanotechnologies such as active nanostructures,
      integrated nanosystems and heterogeneous molecular nanosystems, whereas more
      basic nanotechnologies such as passive nanostructures mainly pose technical
      difficulties. In this paper I argue that fundamental ethical issues are already
      at stake with this more basic kind of nanotechnologies and that ethics impacts
      every kind of nanotechnologies, already from the simplest kind of engineered
      nanoproducts. These ethical issues are mainly associated with the social
      desirability of nanotechnologies, with the difficulties to define
      nanotechnologies properly, with the important uncertainties surrounding
      nanotechnologies, with the threat of 'nano-divide', and with nanotechnology as
      'dual-use technology'.

PMID- 22611459
TI  - A Pneumococcal Carriage Study in Danish Pre-school Children before the
      Introduction of Pneumococcal Conjugate Vaccination.
AB  - We present data on pneumococcal carriage before the introduction of the
      heptavalent-pneumococcal conjugated vaccine (PCV7) in Denmark. In the pre-PCV7
      period, the incidence of invasive pneumococcal disease (IPD) among children
      younger than 5 years was approximately 25 per 100.000 population, with the
      highest incidence rates observed in children younger than 2 years of age. The
      study included 437 children aged 12-72 months attending day care centres (DCC)
      and was conducted during 48 months. In total, 56% (n=247) of children were
      pneumococcal carriers with the highest prevalence in children aged 12-23 months
      (69%), the proportion significantly declining with increasing age. PCV7 serotypes
      accounted for 33%, PCV10 for 34%, and PCV13 for 57% of all carried isolates. The
      proportion of serotypes included in the three conjugate vaccines was higher among
      IPD isolates compared to carrier isolates (range 35- 90%). We found that the
      frequency of carriage was high among Danish pre-school children attending DCC and
      serotypes were not frequently covered by PCV7 in the pre-PCV7 period.

PMID- 22611460
TI  - The association of septic thrombophlebitis with septic pulmonary embolism in
      adults.
AB  - BACKGROUND: There have been an increasing number of pediatric reports of septic
      pulmonary embolism in the setting of septic thrombophlebitis adjacent to a
      primary infectious source. METHODS: Retrospective review at an urban hospital. A
      total of five adults with a documented primary infectious source, adjacent septic
      thrombophlebitis and septic pulmonary embolism were identified between 2000 and
      2011. RESULTS: The predominant symptoms on presentation were fever and pleuritic
      chest pain, followed by chills and cough. S. aureus was the pathogen in 4
      patients. Only one case had echocardiographic evidence of endocarditis. All
      patients received IV antibiotics and anticoagulation therapy. No new embolic
      events or central nervous system complications were noted. CONCLUSIONS: The triad
      of extrapulmonary infection, contiguous septic thrombophlebitis and septic
      pulmonary embolism is present in adult as well as pediatric populations. The use
      of systemic anticoagulation with appropriate antibiotics resulted in clinical and
      radiologic improvement but no significant complications.

PMID- 22611461
TI  - Pilot Evaluation of RT-PCR/Electrospray Ionization Mass Spectrometry (PLEX-ID/Flu
      assay) on Influenza-Positive Specimens.
AB  - The PLEX-ID/Flu assay has been recently developed to enable the detection and
      typing of influenza viruses based on the RT-PCR/electrospray ionization mass
      spectrometry technology.This novel assay was evaluated for typing performance on
      201 positive influenza A or B nasopharyngeal swab specimens (NPS) detected by
      real-time RT-PCR during the 2010-2011 season. The PLEX-ID/Flu assay detected and
      characterized 91.3% and 95.3% of all influenza A and B samples, respectively. All
      non-typeable influenza A and B specimens by the assay showed low viral loads with
      threshold cycle values >= 33. Taken together, and although our results need to be
      confirmed by further prospective studies, the PLEX-ID/Flu assay detected
      positively and gave a typing result for 93% of all NPS detected positively by
      real-time RT-PCR, thus suggesting a potential role for influenza virus
      surveillance among other techniques.

PMID- 22611462
TI  - Late onset retinoblastoma presenting with vitreous haemorrhage.
AB  - Our work describes the management of young patients who presents with vitreous
      haemorrhage. It is important to note that the causes differ significantly from
      adults with vitreous haemorrhage.A 16-year old patient presented with vitreous
      haemorrhage. B-scan ultrasonography showed hypodense elements in the retina. A
      vascularized gelatinous mass was revealed after vitrectomy. Later the patient
      developed white cysts in the anterior chamber and histological findings were
      indicative of a retinoblastoma. The patient was enucleated and the diagnosis of
      retinoblastoma was confirmed. Intraocular surgery in young people with unknown
      retinoblastoma enhances the risk of metastasis development, orbital recurrence
      and death. Unexplained vitreous haemorrhage can obscure the view of a tumour but
      ultrasonic findings of a retinal mass calls for further imaging e.g. through MRI.
      The case illustrates the importance of excluding intraocular malignancy and
      advises a limited use of surgery in the initial examination of vitreous
      haemorrhage in young people.

PMID- 22611463
TI  - Pharmacogenomics in Primary Care: A Crucial Entry Point for Global Personalized
      Medicine?

PMID- 22611464
TI  - Microbe-specific C3b deposition in the horseshoe crab complement system in a
      C2/factor B-dependent or -independent manner.
AB  - Complement C3 plays an essential role in the opsonization of pathogens in the
      mammalian complement system, whereas the molecular mechanism underlying C3
      activation in invertebrates remains unknown. To understand the molecular
      mechanism of C3b deposition on microbes, we characterized two types of C2/factor
      B homologs (designated TtC2/Bf-1 and TtC2/Bf-2) identified from the horseshoe
      crab Tachypleus tridentatus. Although the domain architectures of TtC2/Bf-1 and
      TtC2/Bf-2 were identical to those of mammalian homologs, they contained five
      repeated and seven-repeated complement control protein domains at their N
      terminal regions, respectively. TtC2/Bf-1 and TtC2/Bf-2 were synthesized and
      glycosylated in hemocytes and secreted to hemolymph plasma, which existed in a
      complex with C3 (TtC3), and their activation by microbes was absolutely Mg(2+)
      dependent. Flow cytometric analysis revealed that TtC3b deposition was Mg(2+)
      dependent on Gram-positive bacteria or fungi, but not on Gram-negative bacteria.
      Moreover, this analysis demonstrated that Ca(2+)-dependent lectins (C-reactive
      protein-1 and tachylectin-5A) were required for TtC3b deposition on Gram-positive
      bacteria, and that a Ca(2+)-independent lectin (Tachypleus plasma lectin-1) was
      definitely indispensable for TtC3b deposition on fungi. In contrast, a horseshoe
      crab lipopolysaccharide-sensitive protease factor C was necessary and sufficient
      to deposit TtC3b on Gram-negative bacteria. We conclude that plasma lectins and
      factor C play key roles in microbe-specific TtC3b deposition in a C2/factor B
      dependent or -independent manner.

PMID- 22611465
TI  - BRITER: a BMP responsive osteoblast reporter cell line.
AB  - BACKGROUND: BMP signaling pathway is critical for vertebrate development and
      tissue homeostasis. High-throughput molecular genetic screening may reveal novel
      players regulating BMP signaling response while chemical genetic screening of BMP
      signaling modifiers may have clinical significance. It is therefore important to
      generate a cell-based tool to execute such screens. METHODOLOGY/PRINCIPAL
      FINDINGS: We have established a BMP responsive reporter cell line by stably
      integrating a BMP responsive dual luciferase reporter construct in the
      immortalized calvarial osteoblast cells isolated from tamoxifen inducible Bmp2;
      Bmp4 double conditional knockout mouse strain. This cell line, named BRITER (BMP
      Responsive Immortalized Reporter cell line), responds robustly, promptly and
      specifically to exogenously added BMP2 protein. The sensitivity to added BMP may
      be further increased by depleting the endogenous BMP2 and BMP4 proteins.
      CONCLUSION: As the dynamic range of the assay (for BMP responsiveness) is very
      high for BRITER and as it responds specifically and promptly to exogenously added
      BMP2 protein, BRITER may be used effectively for chemical or molecular genetic
      screening for BMP signaling modifiers. Identification of novel molecular players
      capable of influencing BMP signaling pathway may have clinical significance.

PMID- 22611466
TI  - Taste Enhancement by Pulsatile Stimulation Is Receptor Based But Independent of
      Receptor Type.
AB  - Effects of subjects' taste sensitivity (expressed as taste detection threshold),
      tastant quality and taste transduction mechanism on pulsation-induced taste
      enhancement were tested. Taste intensities of pulsatile MSG and NaCl stimuli at
      pulsation periods below, at and above individual taste fusion periods (TFP in
      seconds) were compared to taste intensities of a continuous reference of the same
      net tastant concentration and quality. In line with results previously reported
      for sucrose, pulsation-induced taste enhancement peaked around TFP for both MSG
      and NaCl and did not require perception of tastant pulsation. TFP and pulsation
      effects were independent of the taste transduction mechanism (G-protein-coupled
      receptor for MSG versus ion-channel for NaCl). The absence of a relation between
      TFP and taste sensitivity suggests that temporal gustatory resolution and taste
      sensitivity are not necessarily influenced by the same factors. The results
      support earlier findings that early stages of taste transduction are involved in
      pulsation-induced taste enhancement. Pulsation-induced taste enhancement is
      determined by the pulsation rate (i.e. TFP) which is longer for MSG than NaCl.
      This is probably due to the tastant-specific interaction with the receptor rather
      than the taste transduction mechanism (G-protein-coupled receptor versus ion
      channel) involved.

PMID- 22611468
TI  - Angiotensin II-inhibition: effect on Alzheimer's pathology in the aged triple
      transgenic mouse.
AB  - Reducing excessive accumulation of amyloid-beta (Abeta) in Alzheimer's disease
      (AD) is a key objective of most AD therapies, and inhibition of angiotensin
      converting enzyme (ACE) may delay onset or progression of AD. The effects of an
      ACE-inhibitor (ACE-I) and an angiotensin II receptor blocker (ARB) on Abeta and
      tau pathology in a triple transgenic (3xTGAD) mouse model of AD were
      investigated. 9-10month 3xTGAD mice were treated with ARB, ACE-I or vehicle for 6
      months. Mean arterial blood pressure (MABP) was measured periodically and mice
      were assessed behaviourally. Abeta, phospho-tau, amyloid precursor protein (APP)
      and ACE activity were analysed. MABP was significantly reduced at 2 weeks and 3
      months in the ACE-I group and at 3 months in the ARB group, compared to vehicle.
      Neither drug altered performance of 3xTGAD mice in Morris Water Maze or T-maze,
      nor were Abeta, tau immunolabelling or APP levels altered. ACE-I significantly
      reduced ACE activity in kidney. Prolonged treatment with ACE-I or ARB does not
      affect Abeta or phospho-tau accumulation in brains of aged 3xTGAD mice.

PMID- 22611467
TI  - Long non-coding RNAs: versatile master regulators of gene expression and crucial
      players in cancer.
AB  - With rapid development of sequencing technologies such as deep sequencing and
      whole genome high-density tiling array, we now know that most of the "junk"
      genomic sequences are transcribed as non-coding RNAs (ncRNAs). A large number of
      long ncRNA transcripts (> 200bp) have been identified, and these long ncRNAs
      (LncRNAs) are found to be crucial regulators for epigenetic modulation,
      transcription, and translation. In this review, we briefly summarize the
      regulatory function of LncRNAs with a particular focus on the underlying
      mechanisms of LncRNAs in oncogenesis, tumor metastasis and suppression.

PMID- 22611469
TI  - alpha(V)beta(6) integrin expression is induced in the POET and Pten(pc-/-) mouse
      models of prostatic inflammation and prostatic adenocarcinoma.
AB  - Chronic inflammation is proposed to prime the development of prostate cancer.
      However, the mechanisms of prostate cancer initiation and development are not
      completely understood. The alpha(v)beta(6) integrin has been shown to play a role
      in epithelial development, wound healing and some epithelial cancers [1, 2].
      Here, we investigate the expression of alpha(v)beta(6) in mouse models of
      prostatic inflammation and prostate cancer to establish a possible relationship
      between inflammation of the prostate, alpha(v)beta(6) expression and the
      progression of prostate cancer. Using immunohistochemical techniques, we show
      expression of alpha(v)beta(6) in two in vivo mouse models; the Pten(pc)-/- model
      containing a prostate- specific Pten tumor suppressor deletion that causes
      cancer, and the prostate ovalbumin-expressing transgenic (POET) inflammation
      mouse model. We show that the alpha(v)beta(6) integrin is induced in prostate
      cancer and inflammation in vivo in these two mouse models. alpha(v)beta(6) is
      expressed in all the mice with cancer in the Pten(pc-/-) model but not in age
      matched wild-type mice. In the POET inflammation model, alpha(v)beta(6) is
      expressed in mice injected with activated T-cells, but in none of the control
      mice. In the POET model, we also used real time PCR to assess the expression of
      Transforming Growth Factor Beta 1 (TGFbeta1), a factor in inflammation that is
      activated by alpha(v)beta(6). In conclusion, through in vivo evidence, we
      conclude that alpha(v)beta(6) integrin may be a crucial link between prostatic
      inflammation and prostatic adenocarcinoma.

PMID- 22611470
TI  - Akt blocks the tumor suppressor activity of LKB1 by promoting phosphorylation
      dependent nuclear retention through 14-3-3 proteins.
AB  - The survival kinase Akt and the tumor suppressor LKB1 elicit opposite effects on
      cell proliferation and tumorigenesis. The present study demonstrates that Akt
      acts as an upstream kinase of LKB1 to promote the phosphorylation at Ser334 and
      facilitate its binding to 14-3-3 proteins, resulting in a decreased interaction
      with STE20-related adaptor protein alpha (STRADalpha) and an enhanced nuclear
      accumulation of LKB1. The S334A mutant of LKB1 exhibits impaired binding with 14
      3-3 proteins and is localized predominantly in the cytoplasm, whereas the
      phosphorylation-mimic mutant, S334D, is sequestrated in the nuclei and unable to
      elicit the tumor suppressor function. On the other hand, S334A exerts more potent
      activity than wild type LKB1 in inhibiting the breast cancer cell proliferation
      and tumor growth in mice. These findings suggest that Akt blocks the anti-growth
      signal of LKB1 by triggering a phosphorylation-dependent nuclear sequestration of
      LKB1 through 14-3-3 proteins.

PMID- 22611471
TI  - Cytokines and Toll-like receptor signaling pathways in the terminal ileum of
      hypoxic/hyperoxic neonatal rats: benefits of probiotics supplementation.
AB  - BACKGROUND: Oxidative stress and inflammation are associated with the development
      of inflammatory bowel diseases such as necrotizing enterocolitis. We tested the
      hypothesis that probiotics, prebiotics or synbiotics (a combination of pre- and
      probiotics) is effective for prevention of inflammatory responses to formula
      feeding in the terminal ileum of neonatal rats. METHODS: Neonatal rats were
      exposed to hyperoxia/hypoxia during which they were either maternally-fed or hand
      fed with formula supplemented with probiotics, prebiotics or synbiotics. A non
      supplemented formula group served as controls. Cytokines and genes associated
      with oxidative stress and toll-like receptor signaling were determined in the
      terminal ileum. Data were compared to room air littermates. RESULTS: Exposure to
      hyperoxia/ hypoxia reduced growth accretion in maternally-fed pups. NEC-like
      symptoms and intestinal inflammatory markers were induced with formula feeding.
      Supplementation with probiotics, prebiotics or synbiotics decreased
      proinflammatory cytokines and downregulated genes involved in oxidative stress
      and toll-like receptor pathways, however, the effect was attenuated in
      hyperoxia/hypoxia. CONCLUSIONS: The combination of suboptimal nutrition due to
      removal of breast milk and formula feeding with hyperoxia/hypoxia may increase
      susceptibility to oxidative stress, inflammation, and NEC. Probiotics, prebiotics
      and synbiotics are protective against oxidative stress and inflammation, but
      their efficacy may be reduced when administered during hyperoxia/hypoxia insults.

PMID- 22611472
TI  - High quality DNA obtained with an automated DNA extraction method with 70+ year
      old formalin-fixed celloidin-embedded (FFCE) blocks from the indiana medical
      history museum.
AB  - DNA and RNA have been used as markers of tissue quality and integrity throughout
      the last few decades. In this research study, genomic quality DNA of kidney,
      liver, heart, lung, spleen, and brain were analyzed in tissues from post-mortem
      patients and surgical cancer cases spanning the past century. DNA extraction was
      performed on over 180 samples from: 70+ year old formalin-fixed celloidin
      embedded (FFCE) tissues, formalin-fixed paraffin-embedded (FFPE) tissue samples
      from surgical cases and post-mortem cases from the 1970's, 1980's, 1990's, and
      2000's, tissues fixed in 10% neutral buffered formalin/stored in 70% ethanol from
      the 1990's, 70+ year old tissues fixed in unbuffered formalin of various
      concentrations, and fresh tissue as a control. To extract DNA from FFCE samples
      and ethanol-soaked samples, a modified standard operating procedure was used in
      which all tissues were homogenized, digested with a proteinase K solution for a
      long period of time (24-48 hours), and DNA was extracted using the Autogen
      Flexstar automated extraction machine. To extract DNA from FFPE, all tissues were
      soaked in xylene to remove the paraffin from the tissue prior to digestion, and
      FFPE tissues were not homogenized. The results were as follows: celloidin
      embedded and paraffin-embedded tissues yielded the highest DNA concentration and
      greatest DNA quality, while the formalin in various concentrations, and long term
      formalin/ethanol-stored tissue yielded both the lowest DNA concentration and
      quality of the tissues tested. The average DNA yield for the various fixatives
      was: 367.77 MUg/ mL FFCE, 590.7 MUg/mL FFPE, 53.74 MUg/mL formalin-fixed/70%
      ethanol-stored and 33.2 MUg/mL unbuffered formalin tissues. The average OD
      readings for FFCE, FFPE, formalin-fixed/70% ethanol-stored tissues, and tissues
      fixed in unbuffered formalin were 1.86, 1.87, 1.43, and 1.48 respectively. The
      results show that usable DNA can be extracted from tissue fixed in formalin and
      embedded in celloidin or paraffin from the early 1900's to present, and may be
      amplified through PCR and used for clinical and experimental studies.

PMID- 22611473
TI  - Characterization of surgical models of postoperative tumor recurrence for
      preclinical adjuvant therapy assessment.
AB  - PURPOSE: Nearly 30% of cancer patients undergoing curative surgery succumb to
      distant recurrent disease. Despite large implications and known differences
      between primary and recurrent tumors, preclinical adjuvant therapy evaluation
      frequently occurs only in primary tumors and not recurrent tumors. We
      hypothesized that well characterized and reproducible models of postoperative
      systemic recurrences should be used for preclinical evaluation of adjuvant
      approaches. EXPERIMENTAL DESIGN: We examined traditional animal models of cancer
      surgery that generate systemic cancer recurrences. We also investigated models of
      systemic cancer recurrences that incorporate spontaneously metastatic cell lines
      and surgical resection. For each model, we critiqued feasibility, reproducibility
      and similarity to human recurrence biology. Using our novel model, we then tested
      the adjuvant use of a novel systemic inhibitor of TGF-beta, 1D11. RESULTS:
      Traditional surgical models are confounded by immunologic factors including
      concomitant immunity and perioperative immunosuppression. A superior preclinical
      model of postoperative systemic recurrences incorporates spontaneously metastatic
      cell lines and primary tumor excision. This approach is biologically relevant and
      readily feasible. Using this model, we discovered that "perioperative" TGF-beta
      blockade has strong anti-tumor effects in the setting of advanced disease that
      would not be appreciated in primary tumor cell lines or other surgical models.
      CONCLUSIONS: There are multiple immunologic effects that rendered previous models
      of postoperative cancer recurrences inadequate. Use of spontaneously metastatic
      cell lines followed by surgical resection eliminates these confounders, and best
      resembles the clinical scenario. This preclinical model provides more reliable
      preclinical information when evaluating new adjuvant therapies.

PMID- 22611474
TI  - Identification of an interleukin 13-induced epigenetic signature in allergic
      airway inflammation.
AB  - Epigenetic changes have been implicated in the pathogenesis of asthma. We sought
      to determine if IL13, a key cytokine in airway inflammation and remodeling,
      induced epigenetic DNA methylation and miRNAs expression changes in the airways
      in conjunction with its transcriptional gene regulation. Inducible expression of
      an IL13 transgene in the airways resulted in significant changes in DNA
      methylation in 177 genes, most of which were associated with the IL13
      transcriptional signature in the airways. A large number of genes whose
      expression was induced by IL13 were found to have decreased methylation,
      including those involved in tissue remodeling (Olr1), leukocyte influx (Cxcl3,
      Cxcl5, CSFr2b), and the Th2 response (C3ar1, Chi3l4). Reciprocally, some genes
      whose expression was suppressed were found to have increased methylation (e.g.
      Itga8). In addition, miRNAs were identified with targets for lung development and
      Wnt signaling, amongst others. These results indicate that IL13 confers an
      epigenetic methylation and miRNA signature that accompanies its transcriptional
      program in the airways, which may play a critical role in airway inflammation and
      remodeling.

PMID- 22611475
TI  - Biomarkers of the Hedgehog/Smoothened pathway in healthy volunteers.
AB  - The Hedgehog (Hh) pathway is involved in oncogenic transformation and tumor
      maintenance. The primary objective of this study was to select surrogate tissue
      to measure messenger ribonucleic acid (mRNA) levels of Hh pathway genes for
      measurement of pharmacodynamic effect. Expression of Hh pathway specific genes
      was measured by quantitative real time polymerase chain reaction (qRT-PCR) and
      global gene expression using Affymetrix U133 microarrays. Correlations were made
      between the expression of specific genes determined by qRT-PCR and normalized
      microarray data. Gene ontology analysis using microarray data for a broader set
      of Hh pathway genes was performed to identify additional Hh pathway-related
      markers in the surrogate tissue. RNA extracted from blood, hair follicle, and
      skin obtained from healthy subjects was analyzed by qRT-PCR for 31 genes, whereas
      8 samples were analyzed for a 7-gene subset. Twelve sample sets, each with <=500
      ng total RNA derived from hair, skin, and blood, were analyzed using Affymetrix
      U133 microarrays. Transcripts for several Hh pathway genes were undetectable in
      blood using qRT-PCR. Skin was the most desirable matrix, followed by hair
      follicle. Whether processed by robust multiarray average or microarray suite 5
      (MAS5), expression patterns of individual samples showed co-clustered signals;
      both normalization methods were equally effective for unsupervised analysis. The
      MAS5- normalized probe sets appeared better suited for supervised analysis. This
      work provides the basis for selection of a surrogate tissue and an expression
      analysis-based approach to evaluate pathway-related genes as markers of
      pharmacodynamic effect with novel inhibitors of the Hh pathway.

PMID- 22611476
TI  - Validation of transcatheter left ventricular electromechanical mapping for
      assessment of cardiac function and targeted transendocardial injection in a
      porcine ischemia-reperfusion model.
AB  - Ischemic heart disease, despite advances in treatment, remains the major cause of
      mortality worldwide. NOGA 3D left ventricular electromechanical mapping allows
      accurate determination of cardiac function and precise identification of sites of
      injury. In a porcine model of ischemia-reperfusion injury, we validate the use of
      the NOGA mapping system for assessment of cardiac function along with the Myostar
      injection catheter for directed delivery of therapeutics to localized target
      sites in the setting of acute myocardial injury.

PMID- 22611477
TI  - Pyrrole-Based Antitubulin Agents: Two Distinct Binding Modalities are Predicted
      for C-2 Analogs in the Colchicine Site.
AB  - 3,5-dibromo-4-(3,4-dimethoxyphenyl)-1H-pyrrole-2-carboxylic acid ethyl ester is a
      promising antitubulin lead agent that targets the colchicine site of tubulin. C-2
      analogs were synthesized and tested for microtubule depolymerizing and
      antiproliferative activity. Molecular modeling studies using both GOLD docking
      and HINT (Hydropathic INTeraction) scoring revealed two distinct binding modes
      that explain the structural-activity relationships and are in accord with the
      structural basis of colchicine binding to tubulin. The binding mode of higher
      activity compounds is buried deeper in the site and overlaps well with rings A
      and C of colchicine, while the lower activity binding mode shows fewer critical
      contacts with tubulin. The model distinguishes highly active compounds from those
      with weaker activities and provides novel insights into the colchicine site and
      compound design.

PMID- 22611478
TI  - Ribonuclease-Activated Cancer Prodrug.
AB  - Cancer chemotherapeutic agents often have a narrow therapeutic index that
      challenges the maintenance of a safe and effective dose. Consistent plasma
      concentrations of a drug can be obtained by using a timed-release prodrug
      strategy. We reasoned that a ribonucleoside 3'-phosphate could serve as a pro
      moiety that also increases the hydrophilicity of a cancer chemotherapeutic agent.
      Herein, we report an efficient route for the synthesis of the prodrug uridine 3'
      (4-hydroxytamoxifen phosphate) (UpHT). UpHT demonstrates timed-released
      activation kinetics with a half-life of approximately 4 h at the approximate
      plasma concentration of human pancreatic ribonuclease (RNase 1). MCF-7 breast
      cancer cells treated with UpHT showed decreased proliferation upon co-incubation
      with RNase 1, consistent with the release of the active drug-4-hydroxytamoxifen.
      These data demonstrate the utility of a human plasma enzyme as a useful activator
      of a prodrug.

PMID- 22611479
TI  - Microscopic Perspective on the Adsorption Isotherm of a Heterogeneous Surface.
AB  - Adsorption of dissolved molecules onto solid surfaces can be extremely sensitive
      to the atomic-scale properties of the solute and surface, causing difficulties
      for the design of fluidic systems in industrial, medical and technological
      applications. In this communication, we show that the Langmuir isotherm for
      adsorption of a small molecule to a realistic, heterogeneous surface can be
      predicted from atomic structures of the molecule and surface through molecular
      dynamics (MD) simulations. We highlight the method by studying the adsorption of
      dimethyl-methylphosphonate (DMMP) to amorphous silica substrates and show that
      subtle differences in the atomic-scale surface properties can have drastic
      effects on the Langmuir isotherm. The sensitivity of the method presented is
      sufficient to permit the optimization of fluidic devices and to determine
      fundamental design rules for controlling adsorption at the nanoscale.

PMID- 22611481
TI  - Automatic online spectral calibration of Fourier-domain OCT for robotic surgery.
AB  - We present a new automatic spectral calibration (ASC) method for spectral Domain
      optical coherence tomography (SD-OCT). Our ASC method calibrates the spectral
      mapping of the spectrometer in SD-OCT, and does not require external calibrating
      light source or a commercial spectral analyzer. The ASC method simultaneously
      calibrates the physical pixel spacing of the A-scan in static and dynamic
      environments. Experimental results show that the proposed ASC method can provide
      satisfactory calibration for SD-OCT to achieve high axial resolution and high
      ranging accuracy, without increasing hardware complexity.

PMID- 22611480
TI  - Socio-Technical Systems Analysis in Health Care: A Research Agenda.
AB  - Given the complexity of health care and the 'people' nature of healthcare work
      and delivery, STSA (Sociotechnical Systems Analysis) research is needed to
      address the numerous quality of care problems observed across the world. This
      paper describes open STSA research areas, including workload management,
      physical, cognitive and macroergonomic issues of medical devices and health
      information technologies, STSA in transitions of care, STSA of patient-centered
      care, risk management and patient safety management, resilience, and feedback
      loops between event detection, reporting and analysis and system redesign.

PMID- 22611482
TI  - Sparse OCT: Optimizing compressed sensing in spectral domain optical coherence
      tomography.
AB  - We applied compressed sensing (CS) to spectral domain optical coherence
      tomography (SD-OCT). Namely, CS was applied to the spectral data in
      reconstructing A-mode images. This would eliminate the need for a large amount of
      spectral data for image reconstruction and processing. We tested the CS method by
      randomly undersampling k-space SD-OCT signal. OCT images are reconstructed by
      solving an optimization problem that minimizes the l1 norm to enforce sparsity,
      subject to data consistency constraints. Variable density random sampling and
      uniform density random sampling were studied and compared, which shows the former
      undersampling scheme can achieve accurate signal recovery using less data.

PMID- 22611483
TI  - The Intramolecular Diels-Alder Reaction of Tryptamine-Derived Zincke Aldehydes Is
      a Stepwise Process.
AB  - Computational studies show that the base-mediated intramolecular Diels-Alder of
      tryptamine-derived Zincke aldehydes, used as a key step in the synthesis of the
      Strychnos alkaloids norfluorocurarine and strychnine, proceeds via a stepwise
      pathway. The experimentally determined importance of a potassium counterion in
      the base is explained by its ability to preorganize the Zincke aldehyde diene in
      an s-cis conformation suitable to bicyclization. Computation also supports the
      thermodynamic importance of the generation of a stable enolate in the final
      reaction step. The thermal cycloreversion reaction of the Diels-Alder products is
      also found to proceed in a stepwise manner.

PMID- 22611485
TI  - Achieving universal access for human immunodeficiency virus and tuberculosis:
      potential prevention impact of an integrated multi-disease prevention campaign in
      kenya.
AB  - In 2009, Government of Kenya with key stakeholders implemented an integrated
      multi-disease prevention campaign for water-borne diseases, malaria and HIV in
      Kisii District, Nyanza Province. The three day campaign, targeting 5000 people,
      included testing and counseling (HTC), condoms, long-lasting insecticide-treated
      bednets, and water filters. People with HIV were offered on-site CD4 cell counts,
      condoms, co-trimoxazole, and HIV clinic referral. We analysed the CD4
      distributions from a district hospital cohort, campaign participants and from the
      2007 Kenya Aids Indicator Survey (KAIS). Of the 5198 individuals participating in
      the campaign, all received HTC, 329 (6.3%) tested positive, and 255 (5%) were
      newly diagnosed (median CD4 cell count 536 cells/MUL). The hospital cohort and
      KAIS results included 1,284 initial CD4 counts (median 348/L) and 306 initial CD4
      counts (median 550/MUL), respectively (campaign and KAIS CD4 distributions P =
      0.346; hospital cohort distribution was lower P < 0.001 and P < 0.001). A Nyanza
      Province campaign strategy including ART <350 CD4 cell count could avert
      approximately 35,000 HIV infections and 1,240 TB cases annually. Community-based
      integrated public health campaigns could be a potential solution to reach
      universal access and Millennium Development Goals.

PMID- 22611484
TI  - Trends in Decline of Antiretroviral Resistance among ARV-Experienced Patients in
      the HIV Outpatient Study: 1999-2008.
AB  - Background. Little is known about temporal trends in frequencies of clinically
      relevant ARV resistance mutations in HIV strains from U.S. patients undergoing
      genotypic testing (GT) in routine HIV care. Methods. We analyzed cumulative
      frequency of HIV resistance among patients in the HIV Outpatient Study (HOPS)
      who, during 1999-2008 and while prescribed antiretrovirals, underwent GT with
      plasma HIV RNA >1,000 copies/mL. Exposure >=4 months to each of three major
      antiretroviral classes (NRTI, NNRTI and PI) was defined as triple-class exposure
      (TCE). Results. 906 patients contributed 1,570 GT results. The annual frequency
      of any major resistance mutations decreased during 1999-2008 (88% to 79%, P =
      0.05). Resistance to PIs decreased among PI-exposed patients (71% to 46%, P =
      0.010) as exposure to ritonavir-boosted PIs increased (6% to 81%, P < 0.001). Non
      significant declines were observed in resistance to NRTIs among NRTI-exposed (82%
      to 67%), and triple-class-resistance among TCE patients (66% to 41%), but not to
      NNRTIs among NNRTI-exposed. Conclusions. HIV resistance was common but declined
      in HIV isolates from subgroups of ARV-experienced HOPS patients during 1999-2008.
      Resistance to PIs among PI-exposed patients decreased, possibly due to increased
      representation of patients whose only PI exposures were to boosted PIs.

PMID- 22611486
TI  - Prevalence of Anaemia and Evaluation of Transferrin Receptor (sTfR) in the
      Diagnosis of Iron Deficiency in the Hospitalized Elderly Patients: Anaemia
      Clinical Studies in Chile.
AB  - Iron constitutes the most prevalent nutritional deficiency worldwide. In Chile,
      anaemia epidemiological data is scarce, evaluating mainly children and women. Our
      objective was to determine prevalence of anaemia in an inpatient elderly
      population (>=60 years) and assess the usefulness of sTfR levels analyzed by
      other authors as a good predictor in the differential diagnosis of iron
      deficiency anaemia and anaemia of chronic disease. Method. We studied medical
      patients admitted at Hospital of Valdivia (HV), Chile, in a 2month period. World
      Health Organization criteria were used for anaemia. Results. 391 patients were
      hospitalized, average age 62.5 years, 247 elderly and 99 of which had anaemia.
      Anaemia was normocytic in 88.8%, and we observed: low serum iron in 46.3%, low
      ferritin 10.1%, high TIBC 2%, low % transferrin saturation (Tsat) 40%, and high
      sTfR 25%. Conclusions. As a first figure known in Chile, the prevalence of
      anaemia in the elderly inpatient was 40.1%. Our findings encourage us to promote
      the implementation of sTfR determination in the clinical setting to analyze the
      state of erythropoiesis in patients with chronic diseases wich commonly occurs in
      elderly.

PMID- 22611487
TI  - In Vivo Inflammation Does Not Impair ABCA1-Mediated Cholesterol Efflux Capacity
      of HDL.
AB  - HDL provides atheroprotection by facilitating cholesterol efflex from lipid-laden
      macrophages in the vessel wall. In vitro studies have suggested impaired efflux
      capacity of HDL following inflammatory changes. We assessed the impact of acute
      severe sepsis and mild chronic inflammatory disease on the efflux capacity of
      HDL. We hypothesize that a more severe inflammatory state leads to stronger
      impaired cholesterol efflux capacity. Using lipid-laden THP1 cells and
      fibroblasts we were able to show that efflux capacity of HDL from both patients
      with severe sepsis or with Crohn's disease (active or in remission), either
      isolated using density gradient ultracentrifugation or using apoB precipitation,
      was not impaired. Yet plasma levels of HDL cholesterol and apoA-I were markedly
      lower in patients with sepsis. Based on the current observations we conclude that
      inflammatory disease does not interfere with the capacity of HDL to mediate
      cholesterol efflux. Our findings do not lend support to the biological relevance
      of HDL function changes in vitro.

PMID- 22611488
TI  - Left ventricular longitudinal function assessed by speckle tracking ultrasound
      from a single apical imaging plane.
AB  - Background. Transthoracic ultrasonography of the heart is valuable in monitoring
      and treatment of critically ill patients. Speckle tracking ultrasound (STU) has
      proven valid in estimating left ventricular systolic deformation. The aims of the
      study were to compare conventional and automated STU and to determine whether
      left ventricular systolic deformation could be estimated from one single imaging
      plane. Methods. 2D-echocardiography cine-loops were obtained from 20 patients for
      off-line speckle tracking analysis, consisting of manually tracing of the
      endocardial border (conventional method) or automatically drawn boundaries
      (automated method). Results. We found a bias of 0,6 (95% CI -2.2-3.3) for global
      peak systolic strain comparing the automated and the conventional method.
      Comparing global peak systolic strain of apical 4-chamber cine-loops with
      averaged Global Peak Strain obtained from apical 4, 2 and long axis cine-loops,
      showed a bias of 0.1 (95% CI -3.9-4.0). The agreement between subcostal 4-chamber
      and apical 4-chamber global peak systolic strain was 4.4 (95% CI -3.7-12.5).
      Conclusion. We found good agreement between the conventional and the automated
      method. STU applied to single apical 4-chamber cine-loops is in excellent
      agreement with overall averaged global peak systolic strain, while subcostal 4
      chamber cine-loops proved less compliant with speckle tracking ultrasound.

PMID- 22611489
TI  - Comparison of goal-directed hemodynamic optimization using pulmonary artery
      catheter and transpulmonary thermodilution in combined valve repair: a randomized
      clinical trial.
AB  - Our aim was to compare the effects of goal-directed therapy guided either by
      pulmonary artery catheter (PAC) or by transpulmonary thermodilution (TTD)
      combined with monitoring of oxygen transport on perioperative hemodynamics and
      outcome after complex elective valve surgery. Measurements and Main Results.
      Forty patients were randomized into two equal groups: a PAC group and a TTD
      group. In the PAC group, therapy was guided by mean arterial pressure (MAP),
      cardiac index (CI) and pulmonary artery occlusion pressure (PAOP), whereas in the
      TTD group we additionally used global end-diastolic volume index (GEDVI),
      extravascular lung water index (EVLWI), and oxygen delivery index (DO(2)I). We
      observed a gradual increase in GEDVI, whereas EVLWI and PAOP decreased by 20-30%
      postoperatively (P < 0.05). The TTD group received 20% more fluid accompanied by
      increased stroke volume index and DO(2)I by 15-20% compared to the PAC group (P <
      0.05). Duration of mechanical ventilation was increased by 5.2 hrs in the PAC
      group (P = 0.04). Conclusions. As compared to the PAC-guided algorithm, goal
      directed therapy based on transpulmonary thermodilution and oxygen transport
      increases the volume of fluid therapy, improves hemodynamics and DO(2)I, and
      reduces the duration of respiratory support after complex valve surgery.

PMID- 22611490
TI  - A Pilot Study of Mifepristone in Combat-Related PTSD.
AB  - Background. We obtained pilot data to examine the clinical and neuroendocrine
      effects of short-term mifepristone treatment in male veterans with PTSD. Methods.
      Eight male veterans with military-related PTSD completed a randomized, double
      blind trial of one week of treatment with mifepristone (600 mg/day) or placebo.
      The primary clinical outcome measures were improvement in PTSD symptoms and
      dichotomously defined clinical responder status as measured by the CAPS at one
      month follow-up. Additional outcome measures included self-reported measures of
      PTSD symptom severity, CAPS-2 symptom subscale scores, and morning plasma
      cortisol and ACTH levels. Results. Mifepristone was associated with significant
      improvements in total CAPS-2 score. At one-month follow-up, all four veterans in
      the mifepristone group and one of four veterans in the placebo group achieved
      clinical response; three of four veterans in the mifepristone group and one of
      four veterans in the mifepristone group remitted. Mifepristone treatment was
      associated with acute increases in cortisol and ACTH levels and decreases in
      cytosolic glucocorticoid receptor number in lymphocytes. Conclusions. Further
      controlled trials of the effects of mifepristone and their durability are
      indicated in PTSD. If effective, a short-term pharmacological treatment in PTSD
      could have myriad uses.

PMID- 22611491
TI  - Which depressive symptoms and medication side effects are perceived by patients
      as interfering most with occupational functioning?
AB  - Background. Major depressive disorder (MDD) is associated with significant
      impairment in occupational functioning. This study sought to determine which
      depressive symptoms and medication side effects were perceived by patients with
      MDD to have the greatest interference on work functioning. Methods. 164
      consecutive patients with MDD by DSM-IV criteria completed a standard assessment
      that included a self-rated questionnaire about the degree to which symptoms and
      side effects interfered with work functioning. Results. The symptoms perceived by
      patients as interfering most with work functioning were fatigue and low energy,
      insomnia, concentration and memory problems, anxiety, and irritability. The
      medication side effects rated as interfering most with work functioning were
      daytime sedation, insomnia, headache, and agitation/anxiety. There were no
      differences between men and women in symptoms or side effects that were perceived
      as interfering with work functioning. Limitations. This was a cross-sectional
      study; only subjective assessments of work functioning were obtained; the fact
      that patients were using varied medications acts as a potential confound.
      Conclusions. Specific depressive symptoms and medication side effects were
      perceived by patients as interfering more with occupational functioning than
      others. These factors should be considered in treatment selection (e.g., in the
      choice of antidepressant) in working patients with MDD.

PMID- 22611492
TI  - Basal cell carcinoma of the head and neck region in ethnic chinese.
AB  - Objectives. This study aims to report our experience in the management of HNBCC
      in ethnic Chinese over a 10-year period. Methods. A retrospective review of all
      ethnic Chinese patients with HNBCC treated in a tertiary centre from 1999 to
      2009. Results. From 1999 to 2009, 225 patients underwent surgical excision for
      HNBCC. Majority were elderly female patients. Commonest presentation was a
      pigmented (76.2%) ulcer (64.8%) over the nose (31.6%). Median skin margin taken
      on tumour excision was 2.0 mm; primary skin closure was achieved in 51.8%.
      Postresection skin margin was clear in 75.4%. Of those with inadequate skin
      margins, 56.7% opted for further treatment, 43.4% for observation. Recurrence
      rates were 2.6% and 13.8%, respectively (P = 0.106). Overall recurrence rate was
      5.5%. Conclusions. HNBCC commonly presented as pigmented ulcers over the nose of
      elderly female patients in our locality. Adequate tumour excision +/-
      reconstruction offered the best chance of cure. Reexcision of those with
      inadequate skin margins improved local tumour control.

PMID- 22611493
TI  - Abdominoperineal resection for rectal cancer: is the pelvic drain externalization
      site an independent risk factor for perineal wound healing?
AB  - Aim. The aim of this paper is to investigate if the insertion of the pelvic
      drainage tube via the perineal wound could be considered as an independent risk
      factor for perineal healing disorders, after abdominoperineal resection for
      rectal malignancy. Patients and Methods. The last two decades, 75 patients
      underwent elective abdominoperineal resection for malignancy. In 42 patients
      (56%), the pelvic drain catheter was inserted through the perineal wound (PW
      group), while in the remaining 33 (44%) through a puncture skin wound of the
      perineum (SW group). Patients' data with respect to age (P = 0.136), stage (P >
      0.05), sex (P = 0.188) and comorbidity (P = 0.128) were similar in both groups.
      25 patients (PW versus SW: 8 versus 17, P = 0.0026) underwent neoadjuvant
      radio/chemotherapy. Results. The overall morbidity rate was 36%, but a
      significant increase was revealed in PW group (52.4% versus 9%, P = 0.0007). In
      33.3% of the patients in the PW group, perineal healing was delayed, while in the
      SW group, no delay was noted. Perineal healing disorders were revealed as the
      main source of increased morbidity in this group. Conclusion. The insertion of
      the pelvic drain tube through the perineal wound should be considered as an
      independent risk factor predisposing to perineal healing disorders.

PMID- 22611494
TI  - Pancreatic fistula after pancreatectomy: definitions, risk factors, preventive
      measures, and management-review.
AB  - Resection of pancreas, in particular pancreaticoduodenectomy, is a complex
      procedure, commonly performed in appropriately selected patients with benign and
      malignant disease of the pancreas and periampullary region. Despite significant
      improvements in the safety and efficacy of pancreatic surgery, pancreaticoenteric
      anastomosis continues to be the "Achilles heel" of pancreaticoduodenectomy, due
      to its association with a measurable risk of leakage or failure of healing,
      leading to pancreatic fistula. The morbidity rate after pancreaticoduodenectomy
      remains high in the range of 30% to 65%, although the mortality has significantly
      dropped to below 5%. Most of these complications are related to pancreatic
      fistula, with serious complications of intra-abdominal abscess, postoperative
      bleeding, and multiorgan failure. Several pharmacological and technical
      interventions have been suggested to decrease the pancreatic fistula rate, but
      the results have been controversial. This paper considers definition and
      classification of pancreatic fistula, risk factors, and preventive approach and
      offers management strategy when they do occur.

PMID- 22611496
TI  - The jaw adductor resultant and estimated bite force in primates.
AB  - We reconstructed the jaw adductor resultant in 34 primate species using new data
      on muscle physiological cross-sectional area (PCSA) and data on skull landmarks.
      Based on predictions by Greaves, the resultant should (1) cross the jaw at 30% of
      its length, (2) lie directly posterior to the last molar, and (3) incline more
      anteriorly in primates that need not resist large anteriorly-directed forces. We
      found that the resultant lies significantly posterior to its predicted location,
      is significantly posterior to the last molar, and is significantly more
      anteriorly inclined in folivores than in frugivores. Perhaps primates emphasize
      avoiding temporomandibular joint distraction and/or wide gapes at the expense of
      bite force. Our exploration of trends in the data revealed that estimated bite
      force varies with body mass (but not diet) and is significantly greater in
      strepsirrhines than in anthropoids. This might be related to greater contribution
      from the balancing-side jaw adductors in anthropoids.

PMID- 22611497
TI  - Morphometric analysis of cranial shape in fossil and recent euprimates.
AB  - Quantitative analysis of morphology allows for identification of subtle
      evolutionary patterns or convergences in anatomy that can aid ecological
      reconstructions of extinct taxa. This study explores diversity and convergence in
      cranial morphology across living and fossil primates using geometric
      morphometrics. 33 3D landmarks were gathered from 34 genera of euprimates (382
      specimens), including the Eocene adapiforms Adapis and Leptadapis and Quaternary
      lemurs Archaeolemur, Palaeopropithecus, and Megaladapis. Landmark data was
      treated with Procrustes superimposition to remove all nonshape differences and
      then subjected to principal components analysis and linear discriminant function
      analysis. Haplorhines and strepsirrhines were well separated in morphospace along
      the major components of variation, largely reflecting differences in relative
      skull length and width and facial depth. Most adapiforms fell within or close to
      strepsirrhine space, while Quaternary lemurs deviated from extant strepsirrhines,
      either exploring new regions of morphospace or converging on haplorhines. Fossil
      taxa significantly increased the area of morphospace occupied by strepsirrhines.
      However, recent haplorhines showed significantly greater cranial disparity than
      strepsirrhines, even with the inclusion of the unusual Quaternary lemurs,
      demonstrating that differences in primate cranial disparity are likely real and
      not simply an artefact of recent megafaunal extinctions.

PMID- 22611495
TI  - Implication of mitochondrial cytoprotection in human islet isolation and
      transplantation.
AB  - Islet transplantation is a promising therapy for type 1 diabetes mellitus;
      however, success rates in achieving both short- and long-term insulin
      independence are not consistent, due in part to inconsistent islet quality and
      quantity caused by the complex nature and multistep process of islet isolation
      and transplantation. Since the introduction of the Edmonton Protocol in 2000,
      more attention has been placed on preserving mitochondrial function as increasing
      evidences suggest that impaired mitochondrial integrity can adversely affect
      clinical outcomes. Some recent studies have demonstrated that it is possible to
      achieve islet cytoprotection by maintaining mitochondrial function and
      subsequently to improve islet transplantation outcomes. However, the benefits of
      mitoprotection in many cases are controversial and the underlying mechanisms are
      unclear. This article summarizes the recent progress associated with
      mitochondrial cytoprotection in each step of the islet isolation and
      transplantation process, as well as islet potency and viability assays based on
      the measurement of mitochondrial integrity. In addition, we briefly discuss
      immunosuppression side effects on islet graft function and how transplant site
      selection affects islet engraftment and clinical outcomes.

PMID- 22611499
TI  - Biotechnological tools for environmental sustainability: prospects and challenges
      for environments in Nigeria-a standard review.
AB  - The environment is a very important component necessary for the existence of both
      man and other biotic organisms. The degree of sustainability of the physical
      environment is an index of the survival and well-being of the entire components
      in it. Additionally, it is not sufficient to try disposing toxic/deleterious
      substances with any known method. The best method of sustaining the environment
      is such that returns back all the components (wastes) in a recyclable way so that
      the waste becomes useful and helps the biotic and abiotic relationship to
      maintain an aesthetic and healthy equilibrium that characterizes an ideal
      environment. In this study, the method investigated includes biological method of
      environmental sustainability which seeks to investigate the various
      biotechnological tools (biotools) in current use and those undergoing
      investigations for future use.

PMID- 22611500
TI  - Chitosan-hyaluronate hybrid gel intraarticular injection delays osteoarthritis
      progression and reduces pain in a rat meniscectomy model as compared to saline
      and hyaluronate treatment.
AB  - Chitosan-Hyaluronate hybrid gel (CHHG) is a self-forming thermo-responsive
      hydrogel. The current study was undertaken in order to assess the effect of CHHG
      on rat's surgically induced osteoarthritis. Methods. Thirteen rats were included
      in the study. In all rats weight-bearing was assessed using a Linton
      Incapacitance tester. All rats underwent bilateral medial partial meniscectomy.
      Four rats received a saline injection in the control knee and a 200-microliter
      injection of CHHG in the experimental knee. Five rats received a high-molecular
      weight hyaluronate injection to the control knee and a 200-microliter injection
      of CHHG in the experimental knee. Four rats underwent the same surgical
      procedure, allowed to recuperate for seven days and then CHHG and hyaluronate
      were injected. The animals were followed for 6 weeks. Two weeks after injection
      of a therapeutic substance the amount of weight-bearing on each knee was
      evaluated using a Linton Incapacitance meter. Results. Two weeks after induction
      of osteoarthritis there is less pain in the CHHG-treated knee than in the control
      treated knee, as determined using a Lintron Incapacitance meter. After six-weeks
      the histological appearance of the CHHG-treated knee was superior to that of the
      controls. This is indicated by thicker cartilage remaining on the medial femoral
      condyle as well as less cyst formation in the CHHG-treated knee. Discussion. CHHG
      appears to delay progression of osteoarthritis and lessen pain in a rat
      surgically-induced knee osteoarthritis model. These results support other
      published results, indicating that there is an ameliorative effect of chitosan on
      human and rabbit osteoarthritis.

PMID- 22611501
TI  - Marginal sealing durability of two contemporary self-etch adhesives.
AB  - Introduction. Sealing abilities of two self-etch adhesives were evaluated after
      two aging processes: storage in water and thermocycling. Materials and Methods.
      Cl V cavities were prepared on the buccal and lingual aspects of 48 human
      premolars, with cervical margins 1 mm below the CEJ. Clearfil Protect Bond (CPB)
      and BeautiBond (BB) (two-step and one-step self-etch adhesives, resp.) were
      applied, each to half of the cavities and restored with composite resin. Each
      group was randomly subdivided into 4 subgroups (n = 12) and evaluated for dye
      penetration after 24 hours, after 3000 thermocycling rounds, after a 6-month
      water storage, and after 3000 thermocycling rounds plus 6-month water storage,
      respectively. Data was analyzed using SPSS 11.5 and Kruskal-Wallis and Mann
      Whitney U tests (alpha = 0.05). Results. There were no significant differences in
      enamel and dentin microleakage between the adhesives (P = 0.683; P = 0.154).
      Furthermore, no significant differences were observed in enamel microleakage of
      each one of CPB and BB (P = 0.061 and P = 0.318, resp.). However, significant
      decrease was observed in subgroups 3 and 4 (P = 0.001) for CPB dentinal margins.
      Conclusion. In this study, limited aging procedures had no influence on marginal
      integrity of composite resin restorations bonded with self-etch adhesives of CPB
      and BB. Furthermore, CPB dentinal sealing improved after aging.

PMID- 22611502
TI  - Failure to diagnose phaeochromocytoma preoperatively: a case report and review of
      diagnostic criteria.
AB  - We present a case in which phaeochromocytoma was not diagnosed preoperatively
      despite extensive investigation. There was significant haemodynamic instability
      during surgery. We review current diagnostic criteria with a view to reducing
      such a risk in future.

PMID- 22611503
TI  - Primary breast angiosarcoma: avoiding a common trap.
AB  - Background. Primary breast angiosarcoma is a rare entity. Case. Initial diagnosis
      was a benign hemangioma at core biopsy. Wide local excision was performed, with
      positive margins. Pathology after surgery reported a moderately differentiated
      angiosarcoma. Tumor was finally treated using mastectomy and radiations. She
      developed a second angiosarcoma in contralateral breast, with an initial
      diagnosis on core biopsy of an atypical vascular lesion and was again treated
      using mastectomy and radiations. She developed bones and lung metastases.
      Conclusion. Primary breast angiosarcoma is a rare entity often difficult to
      diagnose on core biopsy, and a benign differential diagnosis is frequent. A
      highly vascular breast mass should always be considered malignant until proven
      otherwise. Surgical treatment seems to be the best course of action. There is a
      lack of data proving efficacy of adjuvant chemotherapy and radiation therapy.

PMID- 22611504
TI  - Multiple Conjunctival Papillomas of Eyelid Margins in Pemphigus vulgaris.
AB  - Ocular involvement in pemphigus vulgaris (PV) ranges from mild conjuctivits to
      conjunctival blisters and rarely prominent erosions of the bulbar and palpebral
      conjunctiva which may be found at the eyelid margin. We report two unusual cases
      of PV patients presenting with multiple conjunctival papillomatous lesions of the
      eyelids margins.

PMID- 22611498
TI  - Endothelial dysfunction and diabetes: effects on angiogenesis, vascular
      remodeling, and wound healing.
AB  - Diabetes mellitus (DM) is a chronic metabolic disorder characterized by
      inappropriate hyperglycemia due to lack of or resistance to insulin. Patients
      with DM are frequently afflicted with ischemic vascular disease or wound healing
      defect. It is well known that type 2 DM causes amplification of the
      atherosclerotic process, endothelial cell dysfunction, glycosylation of
      extracellular matrix proteins, and vascular denervation. These complications
      ultimately lead to impairment of neovascularization and diabetic wound healing.
      Therapeutic angiogenesis remains an attractive treatment modality for chronic
      ischemic disorders including PAD and/or diabetic wound healing. Many experimental
      studies have identified better approaches for diabetic cardiovascular
      complications, however, successful clinical translation has been limited possibly
      due to the narrow therapeutic targets of these agents or the lack of rigorous
      evaluation of pathology and therapeutic mechanisms in experimental models of
      disease. This paper discusses the current body of evidence identifying
      endothelial dysfunction and impaired angiogenesis during diabetes.

PMID- 22611505
TI  - Late-onset endophthalmitis secondary to exposed glaucoma tube implant in a rare
      case of paediatric glaucoma.
AB  - Glaucoma drainage implants (GDIs) are used to treat paediatric glaucoma resistant
      to conventional medical and surgical treatment, achieving good intraocular
      pressure (IOP) control and long-term success. Late endophthalmitis is a rare
      complication that may develop following GDI surgery. A 17-year-old male presented
      with acute endophthalmitis 2 years after Ahmed glaucoma valve implantation with
      pericardial patch graft for management of refractory glaucoma secondary to
      congenital ectropion uveae. The glaucoma tube was exposed due to erosion of the
      overlying conjunctiva with no visible pericardial graft. After control of active
      infection, he underwent tube revision surgery whereby the exposed tube was
      retained and repatched with a double-thickness pericardial patch graft. He did
      well following surgery with good control of IOP and restoration of vision.
      Conjunctival dehiscence with graft melting over the GDI tube presented a major
      risk factor for endophthalmitis. Prompt surgical revision of an exposed tube is
      highly recommended to avoid ocular morbidity.

PMID- 22611506
TI  - Bilateral optic neuritis associated with the use of infliximab.
AB  - A 40 year old man was admitted with a 2 weeks history of headache, blurred vision
      and bilateral optic neuritis. During the 6 months period prior to admission he
      had treated with infliximab infusions for prsoriasis arthritis. He had 0.2 vision
      in right eye and 0.5 in left Fundoscopy showed moderate disc swelling more on the
      right than on the left side and right-sided splinter heamorrhages at the disc
      margin. The intracranial pressure was normal. He was treated with oral
      methylprednisolone, 100 mg daily for 1 week. His vision improved gradually and
      when seen 10 weeks later his visual acuity was 1.0 in both eyes and he had normal
      visual fields. Optic neuritis is a rare but well recognized serious adverse
      effect of treatments with tumor necrosis factor (TNF) antagonists. This case
      report illustrates a rare but typical side effect of a TNF alpha inhibitors used
      for treating a number of inflammatory diseases. These reactions usually appear
      during first year of treatments and never after the first one or two infusions.
      Both genders and all ages are affected. In some patients the visual defects are
      irreversible.

PMID- 22611507
TI  - Nodular fasciitis of the orbit: a case report and brief review of the literature.
AB  - Nodular fasciitis is a benign, reactive, fibroblastic proliferation in which
      nodules most commonly develop in the subcutaneous or superficial fascia of the
      extremities. The occurrence of these growths in the orbital region is relatively
      rare. Our intent is to report another orbital case of this benign
      fibroproliferative tumor and to provide a brief review of the pertinent medical
      literature. The salient pathologic features of nodular fasciitis are summarized.
      The potential for the misdiagnosis of these benign mesenchymal tumors as a
      malignant sarcomatous neoplasm is discussed. It is important for ophthalmologists
      to be aware of this pathologic entity and its pseudosarcomatous appearance.

PMID- 22611508
TI  - Decompression Retinopathy after ExPRESS Shunt Implantation for Steroid-Induced
      Ocular Hypertension: A Case Report.
AB  - Purpose. To present a unique case of decompression retinopathy after the
      implantation of ExPRESS drainage device. Method. A 25-year-old female patient
      underwent implantation of ExPRESS drainage device in the left eye for the
      management of steroid-induced ocular hypertension. Results. On the postoperative
      day one, best-corrected visual acuity in the left eye was 20/50. Fundus
      examination revealed diffuse intraretinal hemorrhages, some white-centered,
      throughout the retina. There was also marked tortuosity to the retinal
      vasculature and no evidence of choroidal effusion. Intravenous fluorescein
      angiography and indocyanine green did not contribute to the aetiopathogenesis.
      Conclusion. Decompression retinopathy can occur following the implantation of
      ExPRESS drainage device. It is very important to be aware of this complication in
      patients with relatively high intraocular pressure who is planned for filtration
      surgery, including the ExPRESS implant.

PMID- 22611509
TI  - Masquerade syndrome of multicentre primary central nervous system lymphoma.
AB  - Purpose. In Italy we say that the most unlucky things can happen to physicians
      when they get sick, despite the attention of colleagues. To confirm this rumor,
      we report the sad story of a surgeon with bilateral vitreitis and glaucoma
      unresponsive to traditional therapies. Methods/Design. Case report. Results.
      After one year of steroidal and immunosuppressive therapy, a vitrectomy, and a
      trabeculectomy for unresponsive bilateral vitreitis and glaucoma, MRI showed a
      multicentre primary central nervous system lymphoma, which was the underlying
      cause of the masquerade syndrome. Conclusions. All ophthalmologists and
      clinicians must be aware of masquerade syndromes, in order to avoid delays in
      diagnosis.

PMID- 22611510
TI  - Combined anterior sclera staphylectomy and vitrectomy with anterior sclera
      staphyloma and vitreous hemorrhage occurring 38 years after cataract surgery.
AB  - Introduction. To report a case of anterior sclera staphyloma and vitreous
      hemorrhage occurring over 38 years after bilateral cataract surgery. Methods. A
      58-year-old man presented with anterior sclera staphyloma and vitreous hemorrhage
      in the right eye, after bilateral cataract surgery, over 38 years ago. We
      performed combined anterior sclera staphylectomy and vitrectomy of right eye for
      anterior sclera staphyloma and vitreous hemorrhage. Results. Forty-eight months
      after the combined surgery, best-corrected visual acuity was 0.3 (+10.00/-4.50 *
      60) with eutopic stitches of the corneoscleral junction on the superior nasal
      quadrant and a stable ocular surface. Conclusions. This is the first reported
      case of anterior sclera staphyloma with vitreous hemorrhage successfully managed
      by combined surgery.

PMID- 22611511
TI  - Ocular tuberculosis with multiple cerebral abscesses.
AB  - A 23-year-old Malay man presented with headache for one-month duration. It was
      associated with painless blurring of vision of the right eye. He had loss of
      appetite and reduced weight but no night sweats or hemoptysis. His visual acuity
      on the right eye was 6/45 and improved to 6/15 with pinhole. Right fundus
      examination revealed a choroidal tuberculoma located at one disc diameter away
      from optic disc superiorly with mild vitritis. Systemic examinations revealed no
      significant finding. Mantoux test reading was 22 mm with erythrocyte
      sedimentation rate that was 14 mm/h. Other blood investigations were negative
      with normal chest radiography. The computerized tomography scan of the brain
      revealed multiple cerebral abscesses. A clinical diagnosis of right ocular
      tuberculosis with multiple cerebral abscesses was made. He was treated with
      antituberculosis chemotherapy for one year which divided into intensive phase for
      three months and maintenance phase for nine months. Cerebral abscesses resolved
      after three months of antituberculosis drugs and at one-year follow-up, and the
      choroidal tuberculoma resolved completely with scar formation and significant
      macular striae.

PMID- 22611512
TI  - Mesalamine-induced myocarditis and coronary vasculitis in a pediatric ulcerative
      colitis patient: a case report.
AB  - Mesalamine-containing products are often a first-line treatment for ulcerative
      colitis. Severe adverse reactions to these products, including cardiovascular
      toxicity, are rarely seen in pediatric patients. We present a case of a 16-year
      old boy with ulcerative colitis treated with Asacol, a mesalamine-containing
      product, who developed sudden onset chest pain after four weeks on therapy.
      Serial electrocardiograms showed nonspecific ST segment changes, an
      echocardiogram showed mildly decreased left ventricular systolic function with
      mild to moderate left ventricular dilation and coronary ectasia, and his
      troponins were elevated. Following Asacol discontinuation, his chest pain
      resolved, troponins were trending towards normal, left ventricular systolic
      function normalized, and coronary ectasia improved within 24 hours suggesting an
      Asacol-associated severe drug reaction. Mesalamine-induced cardiovascular
      toxicity, although rare, may represent a life-threatening disorder. Therefore,
      every patient presenting with acute chest pain should receive a workup to rule
      out this rare drug-induced disorder.

PMID- 22611513
TI  - Psychosis and silent celiac disease in a down syndrome adolescent: a case report.
AB  - Celiac disease is an autoimmune systemic disorder. It presents gastrointestinal
      and nongastrointestinal manifestations as well as associated conditions. We
      report a 16-year-old Down syndrome girl who presented psychosis symptomatology,
      and she was diagnosed as having silent celiac disease. Olanzapine treatment and
      gluten-free diet were satisfactory. It is necessary to consider celiac disease in
      Down syndrome patients with psychiatric symptoms, mainly psychotic
      symptomatology.

PMID- 22611514
TI  - Transoesophageal echocardiography for monitoring liver surgery: data from a pilot
      study.
AB  - A pilot study aimed to introduce intraoperative monitoring of liver surgery using
      transoesophageal echocardiography (TEE) is described. A set of TEE measurements
      was established as a protocol, consisting of left atrial (LA) dimension at the
      aortic valve plane; mitral velocity flow integral, calculation of stroke volume
      and cardiac output (CO); mitral annular plane systolic excursion; finally, right
      atrial area. A total of 165 measurements (on 21 patients) were performed, 31
      occurring during hypotension. The conclusions reached were during acute blood
      loss LA dimension changed earlier than CVP, and, in one patient, a dynamic left
      ventricular (LV) obstruction was observed; in 3 patients a transient LV systolic
      dysfunction was documented. The comparison between 39 CO paired measurements
      obtained by TEE and PiCCO2 revealed a statistically significant correlation (P <
      0.001, r = 0.83). In this pilot study TEE successfully answered the questions
      raised by the anesthesiologists. Larger cohort studies are needed to address this
      issue.

PMID- 22611515
TI  - Anti-Interleukin-1 Agents in Adult Onset Still's Disease.
AB  - Interleukin 1beta (IL-1beta) is emerging as a master mediator of adult onset
      Still's disease (AOSD) pathogenesis. This pleiotropic cytokine, whose expression
      is under the control of the inflammasome pathway, has a wide type of effects. As
      a key mediator of innate immunity is a potent pyrogen and facilitates
      neutrophilic proliferation and diapedesis into the inflamed tissues, which are
      key AOSD manifestations. The study of proinflammatory cytokines profiles in sera
      and pathological tissues of AOSD patients has shown elevated levels of IL-1beta,
      these levels being highly correlated with disease activity and severity. These
      experimental evidences and the analogy with other autoinflammatory diseases that
      share with AOSD clinical and biological characteristics have suggested the
      blockade of IL-1beta as a possible new therapeutic option for the AOSD,
      especially in conventional therapy resistant cases. Anakinra, the first anti-IL-1
      agent put on the market, has demonstrated capable to induce a rapid response
      sustained over time, especially in systemic forms, where anti-TNFalpha failed to
      control symptoms. While a growing number of evidences supports the utilisation of
      anakinra in AOSD, a new generation of anti-IL1beta antagonists is developing.
      Canakinumab and rilonacept, thanks to their higher affinity and longer half-life,
      could improve the management of this invalidating disease.

PMID- 22611516
TI  - Is Still's Disease an Autoinflammatory Syndrome?
AB  - Systemic juvenile idiopathic arthritis (sJIA), formerly called Still's disease,
      is officially classified as a subset of juvenile idiopathic arthritis (JIA).
      Beside arthritis, it is characterized by prominent systemic features and a marked
      inflammatory response. Even if it is still included in the group of juvenile
      arthritides, sJIA is set apart from all the other forms of JIA. This disorder has
      markedly distinct clinical and laboratory features suggesting a different
      pathogenesis. sJIA does not show any association with HLA genes or with
      autoantibodies and is characterised by an uncontrolled activation of phagocytes
      with hypersecretion of IL-1 and IL-6. Based on clinical and laboratory features,
      as well as on new acquisitions on the pathogenesis, it seems evident that sJIA is
      an autoinflammatory disease related to abnormality in innate immune system. The
      new insights on the pathogenesis of sJIA have therefore dramatically changed the
      approach to treatment, with the development of targeted treatments (anti-IL-1 and
      anti-IL-6 agents) more effective and safer than earlier medications.

PMID- 22611517
TI  - Patterns of pathomorphological changes in acute necrotizing pancreatitis.
AB  - Acinar necrosis is the basic microscopic sign of acute necrotizing pancreatitis
      (ANP). Microcirculation disorder is one of the major factors in the pathogenesis
      and morphogenesis of ANP besides free radicals and damage of enzymatic origin.
      This study is dedicated to the description of microscopic changes in the
      pancreatic stroma in ANP, which leads to destruction of the exocrine pancreas
      with a putative mechanism of endocrine function preservation. This study has been
      carried out on histological samples of pancreas from 224 patients with ANP.
      Histological staining was performed with hematoxylin-eosin (H&E), Masson, Gomori
      methods, and PAS. Microscopy was performed with magnifications of 40*, 100*, and
      400*. Vascular endothelial desquamation, stasis, and sludge are typical changes
      in microcirculation observed in early stages of ANP. Initially, parietal circular
      intravascular microthrombosis accompanied by endothelial desquamation as early as
      stromal swelling occurs with no detectable necrosis. Residual stroma appears
      between areas of necrosis and intact pancreatic tissue. Mucoid swelling is first
      seen in the perivascular spaces extending to the parenchyma and changing into
      fibrinoid imbibition causing further necrosis. Reticulin argyrophilic backbone
      surrounding the pancreatic acini and small ducts decompose. Pancreatic
      structures, which may be preserved in necrotic tissue, include nerves, major
      ducts, and Langerhans islets.

PMID- 22611518
TI  - Socioeconomic and employment status of patients with rheumatoid arthritis in
      Korea.
AB  - OBJECTIVES: This study investigates the prevalence of rheumatoid arthritis (RA)
      by gender and socio-economic characteristics. It also explores the differences in
      the employment status between RA patients and the general population without RA
      in Korea. METHODS: We analyzed data from the Fourth Korea National Health and
      Nutrition Examination Survey (KNHANES IV) conducted from 2007 to 2009. Prevalence
      rates were estimated for female and male patients with RA in terms of age,
      residence, education, income level, and occupation type. The female respondents
      aged 45 to 64 were divided into the RA population and the non-RA population in
      order to compare the employment status between the two groups. RESULTS: The
      annual physician-diagnosed RA prevalence rate was 1.45%. The prevalence rate was
      2.27% for women and 0.62% for men. Individuals with RA had a significantly lower
      employment rate than individuals without RA (41.7 vs. 68.1%). The main reason for
      non-employment among RA patients was health-related problems (47.1%). There was
      statistically significant difference in employment type among the two groups. The
      experience rates for sick leave and sick-in-bed due to RA were 1.7 and 3.9%,
      respectively. CONCLUSION: Middle- and old-aged women accounted for the majority
      of the Korean RA population, which had a significant lower employment rate
      compared to the population without RA for both sexes. RA resulted in considerable
      productivity loss in Korea.

PMID- 22611519
TI  - Associations of religious behavior and experiences with extent of regional
      atrophy in the orbitofrontal cortex during older adulthood.
AB  - The orbitofrontal cortex (OFC) is a region of the brain that has been empirically
      linked with religious or spiritual activity, and atrophy in this region has been
      shown to contribute to serious mental illness in late life. This study used
      structural magnetic resonance imaging to examine the association between
      religious or spiritual factors and volume of the orbitalfrontal cortex (OFC).
      Change in the volume of participants' left and right OFC was measured
      longitudinally over a period of two to eight years. Multiple linear regression
      analyses showed that religious or spiritual factors were related to extent of
      atrophy in the left OFC. Significantly less atrophy of the left OFC was observed
      in participants who reported a life-changing religious or spiritual experience
      during the course of the study, and in members of Protestant religious groups who
      reported being born-again when entering the study. Significantly greater atrophy
      of the left OFC was also associated with more frequent participation in public
      religious worship. No significant relationship was observed between religious or
      spiritual factors and extent of atrophy in the right OFC. These results support
      the presence of a long-term relationship between religious or spiritual
      experience and brain structure, which may have clinical implications.

PMID- 22611520
TI  - Degradation of naturally occurring and engineered antimicrobial peptides by
      proteases.
AB  - We hypothesized that current antimicrobial peptides should be susceptible to
      proteolytic digestion. The antimicrobial peptides: Griffithinsin, RC-101, LL-37,
      LSA-5, PSC-RANTES and DJ007 were degraded by commercially available proteases.
      Two different species of anaerobic vaginal flora, Prevotella bivia and
      Porphyromonas asaccharolytica also degraded the materials. Griffithsin was
      resistant to digestion by 8 of the 9 proteases and the bacteria while LL-37 was
      the most sensitive to protease digestion. These data suggests most of the
      molecules may not survive for very long in the proteolytic rich environments in
      which they are intended to function.

PMID- 22611521
TI  - Is There a Place for Dietary Fiber Supplements in Weight Management?
AB  - Inadequate dietary fiber intake is common in modern diets, especially in
      children. Epidemiological and experimental evidence point to a significant
      association between a lack of fiber intake and ischemic heart disease, stroke
      atherosclerosis, type 2 diabetes, overweight and obesity, insulin resistance,
      hypertension, dyslipidemia, as well as gastrointestinal disorders such as
      diverticulosis, irritable bowel disease, colon cancer, and cholelithiasis. The
      physiological effects of fiber relate to the physical properties of volume,
      viscosity, and water-holding capacity that the fiber imparts to food leading to
      important influences over the energy density of food. Beyond these physical
      properties, fiber directly impacts a complex array of microbiological,
      biochemical, and neurohormonal effects directly through modification of the
      kinetics of digestion and through its metabolism into constituents such as short
      chain fatty acids, which are both energy substrates and important enteroendocrine
      ligands. Of particular interest to clinicians is the important role dietary fiber
      plays in glucoregulation, appetite, and satiety. Supplementation of the diet with
      highly functional fibers may prove to play an important role in long-term obesity
      management.

PMID- 22611522
TI  - Goal Priming in Dieters: Recent Insights and Applications.
AB  - What are the psychological mechanisms that make dieting so challenging in our
      food-rich living environment? Social psychological research on goal priming
      provides a useful framework for answering this question, as well as implications
      for how to enhance dieting success. This review presents and discusses recent
      research which shows that attractive food cues prime the hedonic eating goal in
      dieters, and thus facilitate overeating. However, external cues priming the goal
      of weight control can be used to offset these effects and thus to facilitate
      dieting success, as is demonstrated in both field and laboratory experiments. In
      addition, recent strategies to prevent hedonic effects of attractive food, such
      as mindful attention, can facilitate self-regulation. These recent advances in
      our understanding of dieting behavior have theoretical and practical implications
      for how successful dieting can be facilitated, both by means of individual
      strategies, as well as by environmental changes.

PMID- 22611523
TI  - Attentional Processing of Food Cues in Overweight and Obese Individuals.
AB  - The incentive sensitization model of obesity hypothesizes that obese individuals
      in the western world have acquired an enhanced attention bias to food cues,
      because of the overwhelming exposure to food. This article gives an overview of
      recent studies regarding attention to food and obesity. In general, an
      interesting approach-avoidance pattern in food-related attention has been found
      in overweight/obese individuals in a number of studies. However, it should be
      noted that study results are contradictory. This might be due to methodological
      issues, such as the choice of attention measurements, possibly tapping different
      underlying components of information processing. Although attention research is
      challenging, researchers are encouraged to further explore important issues, such
      as the exact circumstances in which obese persons demonstrate enhanced attention
      to food, the directional relationship between food-related attention bias,
      overeating and weight gain, and the underlying involvement of the reward system.
      Knowledge on these issues could help improve treatment programs.

PMID- 22611525
TI  - Desulfotomaculum varum sp. nov., a moderately thermophilic sulfate-reducing
      bacterium isolated from a microbial mat colonizing a Great Artesian Basin bore
      well runoff channel.
AB  - A strictly anaerobic moderately thermophilic bacterium, designated strain RH04
      3(T) (T = type strain), was isolated from a red colored microbial mat that
      colonizes a Great Artesian Basin (GAB) bore well (Registered Number 17263) runoff
      channel at 66  degrees C. The cells of strain RH04-3(T) were straight to slightly
      curved, sporulating, Gram-positive rods (2.0-5.0 * 1.0 MUm) that grew optimally
      at 50  degrees C (temperature growth range between 37 and 55  degrees C) and at
      pH 7 (pH growth range of 5.0 and 8.5). Growth was inhibited by NaCl
      concentrations >=1.5% (w/v), and by chloramphenicol, streptomycin, tetracycline,
      penicillin and ampicillin. The strain utilized fructose, mannose, glycerol,
      lactate, pyruvate and H(2) in the presence of sulfate, and fermented pyruvate in
      the absence of sulfate. Strain RH04-3(T) reduced sulfate, sulfite, thiosulfate
      and elemental sulfur, but not nitrate, nitrite, iron(III), arsenate(V),
      vanadium(V) or cobalt(III) as terminal electron acceptors. The G + C content of
      DNA was 52.4 +/- 0.8 mol % as determined by the thermal denaturation (Tm) method.
      16S rRNA sequence analysis indicated that strain RH04-3(T) was a member of the
      genus Desulfotomaculum and was most closely related to Desulfotomaculum putei
      (similarity value of 95.2%) and Desulfotomaculum hydrothermale (similarity value
      of 93.6%). On the basis of phylogenetic and phenotypic characteristics, strain
      RH04-3(T) is considered to represent a novel species of the genus
      Desulfotomaculum, for which the name Desulfotomaculum varum sp. nov. is proposed.
      The type strain RH04-3(T) = JCM 16158(T) = KCTC 5794(T).

PMID- 22611526
TI  - Lime pretreatment of sugar beet pulp and evaluation of synergy between ArfA, ManA
      and XynA from Clostridium cellulovorans on the pretreated substrate.
AB  - Sugar beet pulp (SBP) is a waste product from the sugar beet industry and could
      be used as a potential biomass feedstock for second generation biofuel
      technology. Pretreatment of SBP with 'slake lime' (calcium hydroxide) was
      investigated using a 2(3) factorial design and the factors examined included lime
      loading, temperature and time. The pretreatment was evaluated for its ability to
      enhance enzymatic degradation using a combination of three hemicellulases, namely
      ArfA (an arabinofuranosidase), ManA (an endo-mannanase) and XynA (an endo
      xylanase) from C. cellulovorans to determine the conditions under which optimal
      activity was facilitated. Optimal pretreatment conditions were found to be 0.4 g
      lime/g SBP, with 36 h digestion at 40  degrees C. The synergistic interactions
      between ArfA, ManA and XynA from C. cellulovorans were subsequently investigated
      on the pretreated SBP. The highest degree of synergy was observed at a protein
      ratio of 75% ArfA to 25% ManA, with a specific activity of 2.9 U/g protein.
      However, the highest activity was observed at 4.2 U/g protein at 100% ArfA. This
      study demonstrated that lime treatment enhanced enzymatic hydrolysis of SBP. The
      ArfA was the most effective hemicellulase for release of sugars from pretreated
      SBP, but the synergy with the ManA indicated that low levels of mannan in SBP
      were probably masking the access of the ArfA to its substrate. XynA displayed no
      synergy with the other two hemicellulases, indicating that the xylan in the SBP
      was not hampering the access of ArfA or ManA to their substrates and was not
      closely associated with the mannan and arabinan in the SBP.

PMID- 22611524
TI  - Monitoring of microbial hydrocarbon remediation in the soil.
AB  - Bioremediation of hydrocarbon pollutants is advantageous owing to the cost
      effectiveness of the technology and the ubiquity of hydrocarbon-degrading
      microorganisms in the soil. Soil microbial diversity is affected by hydrocarbon
      perturbation, thus selective enrichment of hydrocarbon utilizers occurs.
      Hydrocarbons interact with the soil matrix and soil microorganisms determining
      the fate of the contaminants relative to their chemical nature and microbial
      degradative capabilities, respectively. Provided the polluted soil has requisite
      values for environmental factors that influence microbial activities and there
      are no inhibitors of microbial metabolism, there is a good chance that there will
      be a viable and active population of hydrocarbon-utilizing microorganisms in the
      soil. Microbial methods for monitoring bioremediation of hydrocarbons include
      chemical, biochemical and microbiological molecular indices that measure rates of
      microbial activities to show that in the end the target goal of pollutant
      reduction to a safe and permissible level has been achieved. Enumeration and
      characterization of hydrocarbon degraders, use of micro titer plate-based most
      probable number technique, community level physiological profiling, phospholipid
      fatty acid analysis, 16S rRNA- and other nucleic acid-based molecular
      fingerprinting techniques, metagenomics, microarray analysis, respirometry and
      gas chromatography are some of the methods employed in bio-monitoring of
      hydrocarbon remediation as presented in this review.

PMID- 22611527
TI  - Studies on an alkali-thermostable xylanase from Aspergillus fumigatus MA28.
AB  - An alkalitolerant fungus, Aspergillus fumigatus strain MA28 produced significant
      amounts of cellulase-free xylanase when grown on a variety of agro-wastes. Wheat
      bran as the sole carbon source supported higher xylanase production (8,450 U/L)
      than xylan (7,500 U/L). Soybean meal was observed to be the best nitrogen source
      for xylanase production (9,000 U/L). Optimum medium pH for xylanase production
      was 8 (9,800 U/L), though, significant quantities of the enzyme was also produced
      at pH 7 (8,500 U/L), 9 (8,200 U/L) and 10 (4,600 U/L). The xylanase was purified
      by ammonium sulphate precipitation and carboxymethyl cellulose chromatography,
      and was found to have a molecular weight of 14.4 kDa with a V(max) of 980
      MUmol/min/mg of protein and a K(m) of approximately 4.9 mg/mL. The optimum
      temperature and pH for enzyme activity was 50  degrees C and pH 8, respectively.
      However, the enzyme also showed substantial residual activity at 60-70  degrees C
      (53-75%) and at alkaline pH 8-9 (56-88%).

PMID- 22611528
TI  - Nanocrystalline hydroxyapatite and zinc-doped hydroxyapatite as carrier material
      for controlled delivery of ciprofloxacin.
AB  - In bone disorders infections are common. The concentration of majority of
      antibiotics is very low in the bone tissue. A high local dose can be obtained
      from the ciprofloxacin-loaded hydroxyapatite nanoparticles. The present study is
      aimed at developing the use of hydroxyapatite and zinc-doped hydroxyapatite
      nanoparticles as a carrier for ciprofloxacin drug delivery system. The
      ciprofloxacin-loaded hydroxyapatite and zinc-doped hydroxyapatite have a good
      antibacterial activity against Pseudomonas aeruginosa and Staphylococcus aureus.
      Hydroxyapatite and zinc-doped hydroxyapatite were prepared and characterized
      using X-ray diffraction, Transmission electron microscopy and inductively coupled
      plasma optical emission spectrometry. They were loaded with ciprofloxacin using
      optimized drug loading parameters. Drug loading, in vitro drug release and
      antimicrobial activity were analyzed. The influence of zinc on the controlled
      release of ciprofloxacin was analyzed. The results show that the presence of zinc
      increases the drug release percentage and that the drug was released in a
      controlled manner.

PMID- 22611529
TI  - Pinellia ternata agglutinin produced in Bombyx mori cells exhibits bioactivity.
AB  - Pinellia ternata agglutinin (PTA) is highly homologous to many other monocot
      mannose-binding lectins which reportedly possess antitumor activities. Its
      production in silkworm cells has great application potential because the
      baculovirus expression system can produce post-translationally modified proteins
      at low cost. In the current study, the pta gene was cloned and expressed in
      silkworm cells, and the expressed protein was analyzed using a hemagglutination
      assay. A preliminary in vitro study on its anti-proliferative activity was
      performed. The results show that the recombinant PTA with an apparent molecular
      mass of 29 kDa can hemagglutinate rabbit erythrocytes and this activity can be
      inhibited by D-mannan at a low concentration. In addition, the recombinant
      hemagglutinin exhibited a dose-dependent anti-proliferative activity on hepatoma
      cells. The results of the current study suggest that PTA and other important
      bioactive proteins could be produced by silkworm bioreactor for biomedicine
      research and application.

PMID- 22611530
TI  - [Contemporary Scientific Societies: union or fragmentation?].

PMID- 22611531
TI  - [Perioperative myocardial infarction in coronary bypass surgery: characterization
      of risk factors, clinical pictures and prognosis].
AB  - Perioperative myocardial infarction ( POMI ) in cardiac surgery is an issue that
      deserves to be revisited. OBJECTIVE: To evaluate the risk factors, clinical
      characteristics and prognosis of POMI in high-risk patients ( pts ) undergoing
      coronary bypass surgery ( CABG ). MATERIAL AND METHODS: Retrospective study of
      694 pts undergoing isolated CABG - 252 pts with conventional CABG and 442 pts
      with off-pump CABG - and operated on by 4 surgeons largely experienced in both
      CABG modalities. POMI diagnosis: biochemical criteria - 1 ) late ( at or after 24
      hrs of postoperative period ) troponin ( > 7 ng/mL ) and/or CKMBm ( > 40 ng/mL )
      peak values, with inverted V-shaped curves; 2 ) prolonged troponin release ( ? 48
      hrs ), with a plateau-like curve ( without a well defined peak ) and a
      normal/abnormal CKMBm curve. POMI was diagnosed in 116 pts ( 20.6 % of
      conventional CABG pts and 14.5 % of off-pump CABG pts, p < 0.05 ), that
      constituted Group ( Gr ) A. GrA pts were compared with GrB pts ( without POMI ).
      RESULTS: 1 ) Risk factors ( GrA vs GrB ): female gender 30 % vs 21 % (NS ) ;
      logistic Euroscore 5.6 % vs 5.9 % ( NS ); pre-operative clinical instability 17 %
      vs 23 % ( NS ); incomplete revascularization 39 % vs 38 % ( NS ); multi
      territorial vascular disease 42 % vs 32 % ( p < 0.05 ); diffuse coronary artery
      disease 46 % vs 33 % ( p < 0.025 ); betablocker treatment 58 % vs 70 % ( p <
      0.025 ); statin therapy for > 3 months 56 % vs 81 % ( p < 0.0001 ). 2 ) POMI
      clinical characteristics: asymptomatic/oligosymptomatic 70 %; severe 18 %;
      extensive 15 %. 3 ) Dysrhythmic profile ( GrA vs GrB ): sinus tachycardia > 115
      bpm 9.6 % vs 2.9 % ( p < 0.01 ); atrial pacing for > 4 hrs 5.2 % vs 17.6 % ( p <
      0.01 ); very early ( up to 2 hrs of postoperative period ) atrial tachyarrhythmia
      4.3 % vs 0.9 % ( p < 0.025 ). 4 ) Hospital mortality ( GrA vs GrB ); global 9.6 %
      vs 2.1 % ( p < 0.001 ); cardiovascular 6.1 % vs 0.7 % ( p < 0.001 ). CONCLUSIONS:
      1 ) POMI is more frequent in conventional CABG. 2 ) Although frequently
      asymptomatic or oligosymptomatic, POMI shows adrenergic hyperactivity that
      significantly influences the postoperative dysrhythmic profile. 3 ) POMI is a
      marker of potentially ominous prognosis. 4 ) Instability of multiple coronary
      lesions seems to be the main non-technical POMI risk factor, and an intensive pre
      operative treatment with statins may eventually exert an important role in POMI
      prevention.

PMID- 22611532
TI  - [Aortic valve replacement and concomitant coronary artery bypass: assessing the
      morbi-mortality and recent outcomes].
AB  - Combined coronary artery bypass and aortic valve replacement ( AVR-CABG ) carries
      increased perioperative risk, and tends to have higher-risk patients. The impact
      of pre-operative comorbidities on outcomes after AVR-CABG has not been
      sufficiently evaluated. The purpose of the present study was to analyze risk
      factors, concomitant diseases, postoperative complications and mortality rate in
      patients undergoing AVR-CABG. We retrospectively reviewed all patients who
      underwent AVR-CABG ( n=115, 8.2 % ) at our institution between June 2008 and June
      2011 ( total=1399 ). The average age was 72.8+/-0.7 years-old and 66.1 % were
      male. Preoperative risk factors were: arterial hypertension ( 80.0 % ), diabetes
      ( 34.8 % ), dyslipidemia ( 74.8 % ), smoking ( 19.1 % ), renal failure ( 10.4 %
      ), chronic obstructive pulmonary disease ( 6.1 %) and arterial disease ( 17.4 %
      ). Presenting diagnosis was severe aortic stenosis in 73.9 % and acute coronary
      syndrome in the remaining.Biological valves were implanted in 90.4 % patients and
      69.6 %patients received only one aorto-coronary bypass. The stay in hospital was
      9,4+/-0,6 days. The most important complications were: postoperative bleeding (
      6.1 % ), mediastinitis ( 5.2 % ), heart failure ( 5.2 % ), pulmonary
      insufficiency  ( 5.2 % ) and acute renal failure ( 7.0 % ). Operative mortality
      was 2.6 %.Our results suggest that AVR-CABG is an effective treatment associated
      with low rates of morbimortality, although presented to higher-risk patients.

PMID- 22611533
TI  - [Left ventricle free wall rupture - a 10-year experience].
AB  - The left ventricle free wall rupture is one of the most serious and lethal
      complications associated to myocardial infarction.The most common treatment in
      our days consists in direct closure of the rupture with pericardium or synthetic
      material, applied with the help of histoacryl glue, without extracorporeal
      circulation.Between January 2000 and September 2010, 35 consecutive patients
      underwent operation for left ventricle free wall rupture at our hospital.The mean
      age was 69,5 years and most of the patients were male ( 65,7 % ). 2,9 days was
      the mean time for rupture after infarction and the anterior and lateral wall were
      most frequently involved. 94,7 % of the patients were in shock. Surgery was
      performed without extracorporeal circulation using a patch of pericardium and/or
      Dacron Sauvage, with histoacryl glue in 85,7 % of cases.Mean time of ICU stay was
      7,9 days, in-hospital global mortality 28,6 %. At 2,5 years follow-up, 86 % of
      the patients were alive.Despite the high morbidity and mortality associated to
      surgery, the procedure is now safer, simpler and quick allowing the treatment of
      a situation that conducted to a most certain death without management.

PMID- 22611534
TI  - [Sinister cor triatriatum in an asymptomatic child].
AB  - Cor triatriatum is a very rare congenital abnormality, usually symptomatic during
      childhood. The authors report the case of an asymptomatic 4-years old boy with
      two orifices in the cor triatriatum membrane. Surgical correction, with total
      removal of the membrane, was successfully accomplished.

PMID- 22611535
TI  - ["Straight back" syndrome].
AB  - The authors report the clinical case of a 21-year-old man, with " straight back "
      syndrome, admitted due to prostration and fever. He developed acute pulmonary
      oedema and shock, caused by chordae tendineae rupture of a mixomatous and
      prolapsing mitral valve, with endocarditis. He had also a mixomatous tricuspid
      valve, reduced calibre distal thoracic aorta and celiac trunk stenosis. Mitral
      valve replacement and Vega annuloplasty were performed.  This case illustrates
      the association between " straight back " syndrome and valvular and vascular
      disease and emphasizes that structural heart and vascular abnormalities may be
      present more often in these patients than previously anticipated.

PMID- 22611536
TI  - [Open surgery of infra-renal abdominal aortic aneurysm in octogenarians:
      Redefining the concept of high-risk patient].
AB  - OBJECTIVES: Evaluation of the results of open surgery for infra-renal abdominal
      aortic aneurysm in octogenarians, characterizing the population, risk factors and
      fitness for surgery. Correlation of risk factors and morbidity/mortality.
      METHODS: Review of all octogenarian patients submitted to elective surgery for
      infra-renal abdominal aortic aneurysm between January 2005 and July 2011, in this
      department. Patient demographics and risk factors were analyzed. Kaplan Meier
      survival estimates were performed to assess time-dependent prognosis of the
      surgical procedure. Fitness for surgery was assessed based on Customized
      Probability Index ( CPI ) and quality of life after discharge according to the SF
      8 questionnaire from IQOLATM. Software: IBM(r)SPSS(r)19. RESULTS: A total of 28
      patients were treated during this period ( 82.1 % male, mean age 81.9 +/- 2.3
      years ). Mean follow-up was 29.3 +/- 19.9 months. 17 patients presented with
      abdominal aortic aneurysm and 11 with aorto-iliac aneurysm. There were no cases
      of 30-day mortality and global morbidity was 21.4 %. Mortality was 3.6 % at 1
      year, 17.9 % at 3 years and 21.4 % at 5 years. There was no aneurysm related
      mortality at 5 years. Average length of stay was 13.2 +/- 10.3 days and 7.2 +/-
      7.5 days on ICU. 71.4 % of patients were considered ASA 3 and the average CPI was
      6.2. Average quality of life 30 days post-operatory was 41.8 ( SF-8 ).
      CONCLUSIONS: Elective open repair of infra-renal abdominal aortic aneurysm has
      excellent results in octogenarians, even when comparing with the results of the
      most relevant studies for EVAR. Age is not a contra-indication for surgery and
      fitness for surgery was acceptable in the vast majority of patients. Durability
      of the procedure should not be discarded in this group, as the majority of
      patients are alive 3 years after surgery.

PMID- 22611537
TI  - [Some reflections on the Klippel Trenaunay syndrome: A single entity or an
      association of vascular malformations].
AB  - The author started in the year 2000, in the St Marta Hospital, a consultation for
      congenital vascular malformations, that was extrapolated to the Pulido Valente
      Hospital - CHLN where he continues to see multiple patients with this type of
      pathology, mainly located to the extremities.The Klippel Trenaunay syndrome,
      which was described as a set of anomalies constituted by the presence of a
      cutaneous angiomatous malformation ( port wine stain ), varicose veins and
      gigantism of the limbs, is undoubtedly the most common malformations that he is
      asked to treat. So he thought that it would be interesting to undertake an actual
      review of this pathology.After analyzing the various components in question he 
      concludes that the condition  is undoubtedly a set of malformations ranging from
      a cutaneous component, to the venous and lymphatic malformations and clear the
      osseous component,  that causes the bone dysmorphic appearance, and that  is
      essential a multidisciplinary approach to achieve a final satisfactory
      therapeutic result.

PMID- 22611538
TI  - [Microbiological profile and antibiotic susceptibility patterns of organisms
      isolated from diabetic foot ulcers in a Portuguese hospital].
AB  - OBJECTIVES: To determine the microbiological profile and antibiotic
      susceptibility patterns of organisms isolated from diabetic foot ulcers in a
      Portuguese hospital. METHODS: Microbiological data from ambulatory and
      hospitalized patients with diabetic foot infection during the year 2010 were
      retrospectively analysed. The profile of the isolated organisms was identified,
      regarding their prevalence both in the outpatient and inpatient settings.
      Multidrug-resistant organisms ( MDRO ) under surveillance program at the hospital
      and their antibiotic susceptibility tests were analysed. RESULTS: Gram-positive
      aerobes were most frequently isolated ( 59.6 % ) from outpatient diabetic foot
      ulcers. Staphylococcus was the main genus identified ( 49.8 % ), of which 70.0 %
      were methicillin-sensitive Staphylococcus aureus. Considering samples obtained
      from hospitalized patients, Gram-negative aerobes were dominant ( 63.3 % ),
      mainly Pseudomonas aeruginosa  ( 35.5 % ). Staphylococcus aureus represented 22.2
      % of all isolates, with 60.0 % methicillin-resistance. Extended spectrum beta
      lactamase production and methicillin resistance was noted in 35.0 % and 38.0 % of
      all bacterial isolates, respectively. High levels of resistance were also
      documented for Pseudomonas aeruginosa and Acinetobacter baumannii complex.
      CONCLUSIONS: Epidemiological differences seem to exist between the outpatient and
      inpatient settings concerning the microbiological profile of clinically infected
      diabetic foot ulcers. MDRO are prevalent in this study. Other studies are needed
      in order to adapt empirical therapy to the portuguese reality.

PMID- 22611539
TI  - [Images in medicine: varfarin - induced skin necrosis].

PMID- 22611540
TI  - [Does the Hipocratic Medicine will survive to the contemporaneous technico
      scientific development].

PMID- 22611541
TI  - [The right ventricle in cardiac surgery: the surgeon perspective].
AB  - Right ventricular function is acknowledged as an important prognostic element in
      cardiovascular diseases and cardiac surgery. Although recent years have seen
      significant advances in the exploration of cardiac function, assessing right
      ventricular performance still remains a challenge for the daily practice. The
      right ventricle is a complex structure that cannot be approximated by a simple
      geometric form. It functions in a low impedance system therefore it is sensitive
      to pressure overload. Along with contractility and loading conditions,
      ventricular interactions play an important part in right ventricular function and
      failure. The aims of our review are to describe the main characteristics of RV
      anatomy, function and failure and also to present a perioperative perspective on
      right ventricular dysfunction assessment, its clinical significance and its
      urgent management. Moreover, the advantages of an early diagnosis and preventive
      approach will be discussed. An improved understanding of pathophysiology and
      technologic progress provides us with new pathways in the diagnosis and
      hemodynamic support of these often critically ill patients.

PMID- 22611542
TI  - [Advantages of off-pump coronary bypass  surgery over conventional coronary
      bypass surgery].
AB  - Comparison between off-pump coronary bypass surgery ( OP-CABG )and conventional
      CABG ( C-CABG ) remains a controversial issue. OBJECTIVE: To compare short and
      long term OP-CABG and C-CABG results in high-risk patients ( pts ), in absence of
      usual  bias. MATERIAL AND METHODS: A prospective observational study of 752 pts (
      252 pts with C-CABG and 500 with OP-CABG ) consecutively operated throughout 23
      months by 4 surgeons largely experienced in both CABG modalities. For comparison
      of results, two groups ( Gr ) of pts were constituted - GrA, with 252 C-CABG pts,
      and GrB, with 252 OP-CABG pts - being the pts blindly matched for gender ( female
      sex - 51 pts ), age ( mean of 65 vs 64 yrs ), angiographic data ( 3 - VD / left
      main - 92 % vs 90 % ), additive Euroscore ( mean of 4.6 vs 4.6 ), prior
      myocardial infarction ( 58 % vs 59 % ), history of diabetes ( 48 % vs 49 % ) or
      hypertension ( 83 % vs 83 % ). Other clinical data ( GrA vs GrB ): left
      ventricular dysfunction - 39 % vs 34 % ( NS ); logistic Euroscore - mean of 5.4 %
      vs 5.9 % ( NS ). Surgical results, in-hospital clinical evolution, in-hospital
      costs ( intra-operative and major post-operative costs ), and short-term ( mean
      of 50 days ) and long-term ( mean of 5 years ) follow-up were object of
      evaluation. Results ( GrA vs GrB ): 1 ) Nr of bypasses / pt 2.9 vs 2.4 ( p < 0.01
      ); nr of arterial conduits / pt 1.2 vs 1.2; complete revascularization 60 % vs 60
      %; surgical total time 155 +/- 49 vs 136 +/- 42 min ( p < 0.001 ); surgical total
      time in pts with 3 bypasses 157 +/- 41 vs 156 +/- 37 min ( NS ). 2 ) In-hospital
      post-operative evolution: inotropic support ( IS ) 46 % vs 29 % ( p < 0.001 );
      heavy IS 14 % vs 6 % ( p < 0.025 ) ; uncomplicated post-operative course 18 % vs
      26 % ( p < 0.025 ); significant CV events ( excluding atrial tachyarrhythmias )
      33 % vs 20 % ( p < 0.01 ); infection 22 % vs 14 % ( p < 0.05 ); severe
      complications 22 % vs 9.5 % ( p < 0.001 ); mean intensive care length of stay 4
      vs 3 days ( p < 0.01 ); surgery-to-discharge length of stay 11.3 vs 9.8 days ( p
      ? 0.05 ); in-hospital mortality  ( HM ) 4.4 % vs 2.0 % ( NS ); HM + disabling
      chronic morbidity 7.5 % vs 3.2 % ( p < 0.05 ) . 3 ) In-hospital costs:  intra
      operative  - superposable; post-operative - excess of about  900  euro / pt in
      GrA. 4 ) Short-term follow-up: asymptomatic pts - 75 % vs 85 % ( p < 0.025 );
      post-discharge complications - 8.3 % vs 7.7 % ( NS ); probability of being alive
      and asymptomatic + 17 % in GrB ( p < 0.01 ); mortality 0 % vs 0 %. 5 ) Long-term
      follow-up ( 87 % vs 90 % pts ), at 5 years: pts alive with no clinical evidence
      of active coronary artery disease 72 % vs 75 % ( NS ); significant / severe
      cardiac events of coronary origin 18.8 % vs 9.3 % ( p < 0.025 ); elective PTCA
      4.8 % vs 2.3 % ( NS ); all-cause mortality 11.8 % vs 11.9 %; coronary mortality
      6.9 % vs 4.4 % ( NS ). CONCLUSIONS: In experienced hands and before high-risk
      pts, OP-CABG offers lesser post-operative risks than C-CABG, with clear and
      positive consequences on in-hospital costs and short-term follow-up. During long
      term follow-up, the revascularization benefits obtained by OP-CABG are not
      inferior to those conferred by C-CABG, and a significant reduction of the
      incidence of severe cardiac events can even be seen in a particular subset of
      pts.

PMID- 22611543
TI  - [Prothrombotic events after percutaneous closure of an atrial septal defect].
AB  - We describe the case of a 66 years-old patient, submitted to percutaneous closure
      of an ostium secundum atrial septal defect ( ASD ), with an " Amplatzer ASO 20 mm
      " ( Medical AGA Corp., MN (. There were no immediate complications and no
      residual leak. Eleven days after the procedure, atrial fibrillation ( AF )
      ensued, followed by an acute myocardial infarction ( distal occlusion of the
      circumflex artery ). Three days later, this patient had also a transitory
      ischemic accident. Percutaneous closure of ASD is a procedure that can be
      associated with a few complications, namely AF and thromboembolic events.
      Although common, the use of dual antiplatelet therapy doesn't have an established
      efficacy to prevent these cases.

PMID- 22611544
TI  - [Surgery of bronchiectasis: what have changed in the last ten years?].
AB  - Bronchiectasis is defined as chronic abnormal dilatation and distortion of the
      bronchi. Surgery continues to be play an important role in the treatment of this
      disease especially in focal disease which is both curative.    The objective of
      this study is to characterize the patients who underwent surgical resection of
      bronchiectasis in 10 years and compare them with patients operated by the same
      pathology in the previous 10 years.  We conducted a review of cases of 78
      patients operated in the 2000 ' s and the results were compared with those
      obtained in the study by the same professional service, referring to the previous
      decade.  We assessed sex, age, symptoms, number of years with symptoms,
      complementary exams performed prior to surgery, indications for surgery, previous
      pulmonary diseases, location of bronchiectasis, type of surgical approach, number
      of hospitalization days and complications of surgery.  In the last decade a
      smaller number of patients with bronchiectasis ( 78 versus 119 ) were submitted
      to thoracic surgery. In both groups the right lung and the lower lobes were the
      most affected and the majority of patients was submitted to lobectomy. In the
      last decade a lower percentage of complications was registed ( 6.4 %, versus 15.0
      % (.  The surgery was considered to be curative in 94.9 % and only 91 % in the 90
      ' s.  This study would support the idea that the surgery of bronchiectasis
      continues to be an excellent alternative to the treatment of localized forms of
      the disease and its complications.

PMID- 22611545
TI  - [Nutritional status of patients with critical ischemia of the lower extremities].
AB  - INTRODUCTION: Critical limb ischemia is a manifestation of peripheral arterial
      disease and in Portugal the profile of these patients is yet unknown as well as
      the frequency of hospital malnutrition. The present study aims to contribute to
      the updating of knowledge on the nutritional status of patients with this
      condition. AIM: To evaluate the frequency of malnutrition in hospitalized
      patients with critical lower limb ischemia. METHODOLOGY: A prospective
      longitudinal study was conducted in the University Clinic of Vascular Surgery of
      Hospital Santa Maria between November 2010 and February 2011. Data were collected
      using PG-SGA ( Patient Generated-Subjective Global Assessment ) to assess
      nutritional status. RESULTS: 71 patients were evaluated of whom 21 % ( 22 ) were
      identified as malnourished, 40.8 % ( 29 ) at risk of malnutrition and 28.2 % ( 20
      ) with normal nutritional status.  According to the data, the risk of
      malnutrition is higher in people aged over 75 years ( OR: 5.12, 95 % CI: 3.03
      51.47 ) and diabetic ( OR: 2.73, 95 % CI: 0.88-8.46 ). Concerning to education
      and occupation, the retired individuals ( OR: 3.85, CI: 0.86-17.15 ) and with an
      education level between 1 and 4 years ( OR: 2.64, 95 %CI: 0.78-8.90 ), had an
      increased risk of malnutrition. CONCLUSION: The frequency of malnutrition in
      patients with critical lower limb ischemia was quite high. Data have revealed
      that factors associated with malnutrition in these patients are age, low level of
      education ( less than 4 years ), diabetes and hypertension. To assess nutritional
      status of these patients the most suitable protocol was NRS-2002.

PMID- 22611546
TI  - The need for reintervention is not higher after EVAR: an eight years single
      center experience.
AB  - OBJECTIVE: To evaluate and compare the effectiveness and clinical outcomes of
      abdominal aortic aneurysm treatments. METHODS: The medical records of all
      patients who underwent elective open or endovascular repair of nonruptured infra
      renal abdominal aortic aneurysm from January 2001 to April 2009 were
      retrospectively reviewed. The assessed outcomes were all-cause mortality,
      aneurysm-related mortality, incidence of perioperative complications and
      reinterventions. Patient demographics and procedure characteristics were also
      analysed. RESULTS: One hundred and eighty four consecutive patients were
      included: 107 ( 58 % ) had open surgery and 77 ( 42 % ) had endovascular repair (
      EVAR ). Medical complications were more frequent after open surgery ( 24 % vs 10
      %; p=0.025 ).  There was no perioperative mortality in the EVAR group, whereas in
      open surgery 9 deaths occurred ( 8.4 % in-hospital mortality; p=0.011 ). At 7
      years, all cause mortality was similar in the two groups ( 27 vs 30 %; p=0.34 ).
      There was, however, a persistent difference in aneurysm-related mortality (
      Kaplan-Meier estimates were 9.5 % in the open repair group and 1.5 % in the EVAR
      group; p=0.023 ). Reintervention rates for EVAR were not higher than those for
      open surgery ( at 5 years, 21.2 % vs 21.4 %; p=0.70 ). CONCLUSIONS: In our
      institution, EVAR is associated with lower early mortality and morbidity compared
      to open repair. Despite equivalent late overall survival, endoluminal repair
      offers an aneurysm-related mortality 6 times inferior to open repair. The need
      for reintervention was similar after EVAR or open surgery. In this study setting,
      our findings support endovascular management of large AAAs, even in patients fit
      for open repair.

PMID- 22611547
TI  - [Prosthetic revascularization of the midpopliteal artery through a posterior
      approach: a clinical experience].
AB  - Bypass grafting to the proximal or distal popliteal artery through a lateral
      approach is the most commum surgical technique used to treat patients with femoro
      popliteal obstructive disease. We report all the patients who underwent a bypass
      graft to the midpopliteal artery through a posterior approach, in whom an
      autologous vein was not avalaiable, thus avoiding the use of a prosthetic graft
      implantation in to the infragenicular popliteal artery.  Ten bypass grafts to the
      midpopliteal artery through a posterior approach were performed, for the last 6
      years, in patients with critical limb ischaemia.  Polytetrafluoroethylene ( PTFE
      ) grafts were used in all patients. With a mean follow-up of 16,1 months, the 1
      year primary patency rate was 85,7 % and the 2-year primary patency rate was 66,7
      %.  Bypass grafting to the midpopliteal artery through a posterior approach seems
      to be a safe and sustainable procedure and is an alternative techinique to be
      considered in patients without autologus vein avalaiable, when an above-knee
      bypass grafting is not feasible or when a below-knee prothesis should be avoided.

PMID- 22611548
TI  - [Varicose veins of lower limbs: progress in the surgical management].
AB  - Varicose veins are part of the spectrum of Chronic Venous Disease. They are very
      prevalent, especially among women and involve mainly the great saphenous
      vein.Pathogenesis of varicose veins is complex and multifactorial. There is a
      valvular incompetence as well as a dilation in the vein wall. However, the
      sequence in which these mechanisms occur is unknown. Probably the valves become
      incompetent secondary to vein wall abnormalities.The first description of the
      surgical technique used today came in the transition from the nineteenth to the
      twentieth century. In the last decade, the great debate evolved around the new
      techniques of endovascular radiofrequency and laser ablation. These follow the
      global trend of Medicine to use less invasive techniques.This study, besides
      performing a contextualization and review of concepts about varicose veins,
      especially intends to launch the latest data on the state-of-the-art regarding
      the treatment of this disease, and stands on data collected from Pubmed.It gets
      clear that endovascular techniques are safe and effective, besides revealing
      better results in terms of postoperative morbidity when compared with classic
      surgery. However, the last decade was marked by constant improvements in
      techniques, creating difficulties in interpreting data presented in trials.
      Furthermore, there is progressively greater difficulty in randomizing patients,
      given their preference for less invasive procedures over traditional surgery. New
      trials on the long-term efficacy in addition to detailed analysis of costs will
      also be crucial for the implementation of these new methods.

PMID- 22611549
TI  - [Images in medicine: large right atrial myxoma].

PMID- 22611550
TI  - Archaeal abundance in relation to root and fungal exudation rates.
AB  - Archaea are ubiquitous in forest soils, but little is known about the factors
      regulating their abundance and distribution. Low molecular weight organic
      compounds represent an important energy source for archaea in marine
      environments, and it is reasonable to suspect that archaeal abundance is
      dependent on such compounds in soils as well, represented by, for example, plant
      and fungal exudates. To test this hypothesis, we designed a microcosm experiment
      in which we grew ponderosa pine, sitka spruce, and western hemlock in forest
      soil. Root and mycorrhizal exudation rates were estimated in a 13C pulse-chase
      experiment, and the number of archaeal and bacterial 16S rRNA genes was
      determined by qPCR. Archaeal abundance differed among plant species, and the
      number of archaeal 16S rRNA genes was generally lower in soil receiving high
      concentration of exudates. The mycorrhizal fungi of ponderosa pine seemed to
      favor archaea, while no such effect was found for mycorrhized sitka spruce or
      western hemlock. The low abundance of archaea in the proximity of roots and
      mycorrhiza may be a result of slow growth rates and poor competitive ability of
      archaea vs. bacteria and does not necessarily reflect a lack of heterotrophic
      abilities of the archaeal community.

PMID- 22611552
TI  - Abundance of ammonia-oxidizing bacteria and archaea in industrial and domestic
      wastewater treatment systems.
AB  - Nitrification plays a significant role in the global nitrogen cycle. Ammonia
      oxidation, the first step of nitrification, is performed in wastewater treatment
      by both ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA).
      Most previous studies focused on their distribution in natural environments. In
      this study we qualified and quantified AOB, AOA, total bacteria, and total
      archaea in six different wastewater treatment systems (WTSs) using clone library
      and real-time PCR techniques. The results revealed that wastewater quality was an
      essential factor for the distribution of AOB and AOA in aerobic reactors.
      Although both AOB and AOA were present in all samples and contributed to
      nitrification simultaneously, AOB were the dominant nitrifiers in the three
      industrial WTSs, whereas AOA were dominant in the three domestic WTSs. This
      indicates AOA may be more sensitive to some toxic compounds than AOB. In
      addition, the dominant groups of AOB in the industrial WTSs were Nitrosomonas and
      Nitrosospira; the composition of AOA in the domestic WTSs was very similar,
      possibly due to the same source of raw sewage.

PMID- 22611553
TI  - Centimetre-scale vertical variability of phenoxy acid herbicide mineralization
      potential in aquifer sediment relates to the abundance of tfdA genes.
AB  - Centimetre-scale vertical distribution of mineralization potential was determined
      for 2,4-dichlorophenoxyacetic acid (2,4-D), 4-chloro-2-methylphenoxyacetic acid
      (MCPA) and 2-(4-chloro-2-methylphenoxy)propanoic acid (MCPP) by 96-well
      microplate radiorespirometric analysis in aquifer sediment sampled just below the
      groundwater table. Mineralization of 2,4-D and MCPA was fastest in sediment
      samples taken close to the groundwater table, whereas only minor mineralization
      of MCPP was seen. Considerable variability was exhibited at increasing aquifer
      depth, more so with 2,4-D than with MCPA. This suggests that the abundance of
      MCPA degraders was greater than that of 2,4-D degraders, possibly due to the fact
      that the overlying agricultural soil had long been treated with MCPA.
      Mineralization of 2,4-D and MCPA was followed by increased abundance of tfdA
      class I and class III catabolic genes, which are known to be involved in the
      metabolism of phenoxy acid herbicides. tfdA class III gene copy number was
      approximately 100-fold greater in samples able to mineralize MCPA than in samples
      able to mineralize 2,4-D, suggesting that tfdA class III gene plays a greater
      role in the metabolism of MCPA than of 2,4-D. Degradation rate was found to
      correlate positively with tfdA gene copy number, as well as with the total
      organic carbon content of the sediment.

PMID- 22611555
TI  - [Report - rehabilitation: in search of evidence].

PMID- 22611554
TI  - Gas phase basicities of polyfunctional molecules. Part 3: Amino acids.
AB  - The present article is the third part of a general overview of the gas-phase
      protonation thermochemistry of polyfunctional molecules (first part: Mass
      Spectrom. Rev., 2007, 26:775-835, second part: Mass Spectrom. Rev., 2011, in
      press). This review is devoted to the 20 proteinogenic amino acids and is divided
      in two parts. In the first one, the experimental data obtained during the last 30
      years using the equilibrium, thermokinetic and kinetic methods are presented. A
      general re-assignment of the values originating from these various experiments
      has been done on the basis of the commonly accepted Hunter & Lias 1998 gas-phase
      basicity scale in order to provide an homogeneous set of data. In the second
      part, theoretical investigations on gaseous neutral and protonated amino acids
      are reviewed. Conformational landscapes of both types of species were examined in
      order to provide theoretical protonation thermochemistry based on the truly
      identified most stable conformers. Proton affinities computed at the presently
      highest levels of theory (i.e. composite methods such as Gn procedures) are
      presented. Estimates of thermochemical parameters calculated using a Boltzmann
      distribution of conformers at 298K are also included. Finally, comparison between
      experiment and theory is discussed and a set of evaluated proton affinities, gas
      phase basicities and protonation entropies is proposed.

PMID- 22611551
TI  - Cyanobacterial diversity in the phyllosphere of a mangrove forest.
AB  - The cyanobacterial community colonizing phyllosphere in a well-preserved
      Brazilian mangrove ecosystem was assessed using cultivation-independent molecular
      approaches. Leaves of trees that occupy this environment (Rhizophora
      mangle,Avicennia schaueriana and Laguncularia racemosa) were collected along a
      transect beginning at the margin of the bay and extending upland. The results
      demonstrated that the phyllosphere of R. mangle and L. racemosa harbor similar
      assemblages of cyanobacteria at each point along the transect. A. schaueriana,
      found only in the coastal portions of the transect, was colonized by assemblages
      with lower richness than the other trees. However, the results indicated that
      spatial location was a stronger driver of cyanobacterial community composition
      than plant species. Distinct cyanobacterial communities were observed at each
      location along the coast-to-upland transect. Clone library analysis allowed
      identification of 19 genera of cyanobacteria and demonstrated the presence of
      several uncultivated taxa. A predominance of sequences affiliated with the orders
      Nostocales and Oscillatoriales was observed, with a remarkable number of
      sequences similar to genera Symphyonemopsis/Brasilonema (order Nostocales). The
      results demonstrated that phyllosphere cyanobacteria in this mangrove forest
      ecosystem are influenced by environmental conditions as the primary driver at the
      ecosystem scale, with tree species exerting some effect on community structure at
      the local scale.

PMID- 22611556
TI  - [Prospective multicenter comparison - Orhthopedics: dumb and strong?].

PMID- 22611557
TI  - [Hip fractures - transfusion management after hip surgery].

PMID- 22611558
TI  - [Hip fractures - surgical experience reduces the infection rate].

PMID- 22611559
TI  - [Femoracetabular impingement - easy recording of a complex problem?].

PMID- 22611560
TI  - Shared loci for migraine and epilepsy on chromosomes 14q12-q23 and 12q24.2-q24.3.

PMID- 22611562
TI  - The search for life on Earth and other planets.
AB  - As the NASA rover Curiosity approaches Mars on its quest to look for signs of
      past or present life there and sophisticated instruments like the space
      telescopes Kepler and CoRoT keep discovering additional, more Earth-like planets
      orbiting distant stars, science faces the question of how to spot life on other
      planets. Even here on Earth biotopes remain to be discovered and explored.

PMID- 22611563
TI  - James Franklin Crow (1916-2012).

PMID- 22611564
TI  - Eric Davidson.

PMID- 22611565
TI  - Successful treatment of epidermolysis bullosa acquisita with rituximab therapy.

PMID- 22611566
TI  - Relapsed lymphoma preceded by cold  agglutinin disease.

PMID- 22611567
TI  - Angiotensin II receptor blocker partially ameliorated intrarenal hypoxia in
      chronic kidney disease patients: a pre-/post-study.
AB  - Chronic intrarenal hypoxia has been regarded as a pathogenic factor of
      progressive renal damage. However, the lack of available human data has impeded
      the progress in this field. In this work, blood oxygen level-dependent magnetic
      resonance imaging was used to determine intrarenal oxygen status pre- and post
      angiotensin receptor blockade (olmesartan) treatment in normal subjects, diabetic
      chronic kidney disease (CKD) patients and non-diabetic CKD patients. The mean
      R2*, which represents intrarenal oxygenation, was significantly lower in the
      control group than in the CKD group (12.42 +/- 0.53 /s vs 18.89 +/- 3.15 /s, P <
      0.01), indicating the presence of intrarenal hypoxia in the CKD patients. The
      olmesartan treatment induced a 16.2 +/- 7.7% decrement of the mean R2* in CKD
      patients, suggesting that this drug had an intrarenal hypoxia ameliorating
      effect.

PMID- 22611569
TI  - Retraction. Cardiovascular intubation responses with the Airway Scope(r) and the
      Macintosh laryngoscope.

PMID- 22611568
TI  - Going digital.

PMID- 22611570
TI  - Cooking Bolshevik: Anastas Mikoian and the making of the "Book about Delicious
      and Healthy Food".
AB  - Both one of the most iconic cookbooks of all time and one of the strangest, the
      "Kniga o vkusnoi i zdorovoi pishche" became the culinary bible of the Soviet
      household during the mid-twentieth century. The logical culmination of a decade
      of Soviet culinary evolution under the leadership of Anastas Mikoian, the
      original "Book about Delicious and Healthy Food" is a microcosm of Stalinist
      civilization that exemplifies the contradictory trends making up Soviet politics
      and culture in the late 1930s. Drawing on previously unexamined documents from
      the State Archive of the Russian Federation, Anastas Mikoian's personal papers
      retained in the Russian State Archive of Socio-Political History, as well as
      published primary sources, this article seeks to contextualize the complex tale
      of the cookbook's origins in a broader narrative of the construction of the
      Soviet Union's official food culture under Mikoian's leadership during the 1930s.

PMID- 22611571
TI  - Care workers, care drain, and care chains: reflections on care, migration, and
      citizenship.
AB  - In this article, we discuss a case study that deals with the care chain
      phenomenon and focuses on the question of how Poland and the Ukraine as sending
      countries and Poland as a receiving country are affected and deal with female
      migrant domestic workers. We look at the ways in which these women organize care
      replacement for their families left behind and at those families' care
      strategies. As public discourse in both countries is reacting to the feminization
      of migration in a form that specifically questions the social citizenship
      obligations of these women, we also look at the media portrayal of the situation
      of nonmigrating children. Finally, we explore how different aspects of
      citizenship matter in transnational care work migration movements.

PMID- 22611572
TI  - Hierarchization and segmentation of informal care markets in Slovenia.
AB  - The article is the result of qualitative research of informal care markets in
      Slovenia in the field of childcare, elder care, and cleaning. The author assesses
      Slovenia's position in the "global care chain" and finds that "local care chains"
      prevail in the field of childcare and elder care, while a co-occurrence of female
      gender, "other" ethnicity, and poverty is typical in the field of household
      cleaning. The main emphasis of the article is on the analysis of hierarchization
      of the informal market of care work according to following two criteria: social
      reputation of individual type of care work and citizenship status of care
      workers.

PMID- 22611573
TI  - Transnational spaces of care: migrant nurses in Norway.
AB  - This article argues that international nurse recruitment from Latvia to Norway is
      not a win-win situation. The gains and losses of nurse migration are unevenly
      distributed between sender and receiver countries. On the basis of empirical
      research and interviews with Latvian nurses and families they left behind, this
      article argues that nurse migration transforms families and communities and that
      national health services now become global workplaces. Some decades ago feminist
      research pointed to the fact that the welfare state was based on a male
      breadwinner family and women's unpaid production of care work at home. Today this
      production of unpaid care is "outsourced" from richer to poorer countries and is
      related to an emergence of transnational spaces of care. International nurse
      recruitment and global nurse care chains in Norway increasingly provide the labor
      that prevents the new adult worker model and gender equality politics from being
      disrupted in times where families are overloaded with elder care loads.

PMID- 22611574
TI  - Negotiating user preferences, discrimination, and demand for migrant labour in
      long-term care.
AB  - The restructuring of long-term care for older people has been marked both by the
      role of the market and by the role of migrant labor. This article develops the
      analysis of these processes at the microlevel of the provision of care. It draws
      on data collected as part of a cross-national comparative study on the employment
      of migrant care workers in residential care homes and home care services for
      older people in England and Ireland. The article examines, first, the ways in
      which divisions of race, ethnicity, and citizenship shape the preferences of
      service providers/employers and some service users as regards who provides care.
      Second, it examines how the institutional context of quasi-markets in long-term
      care shapes the negotiation of demand for migrant labor, the racialized
      preferences of individual users, alongside the rights of care workers to non
      discrimination. It is argued that market-oriented policies for personalization,
      as well as for cost containment, raise implications for divisions of race,
      ethnicity, and citizenship in the provision of long-term care. At the same time,
      those divisions point to the limits of framing care in terms of the preferences
      of the individual as opposed to the social relations in which care is embedded.

PMID- 22611575
TI  - Transnational aging careers: on transformation of kinship and citizenship in the
      context of migration among Bulgarian Muslims in Spain.
AB  - This article focuses on "transnational aging careers," a group of elderly
      migrants who are in constant movement between social contexts, families, and
      states. Drawing on a case of Bulgarian Muslim migrants in Spain, I look into the
      ruptures in the structure of care arrangements, kin expectations, and family
      relations, which migration triggers. I suggest that these transformations, albeit
      subtle, lead to reformulation of the fabric of the family. In this way,
      transnational care-motivated mobility affects future security based on kin
      reciprocity. At the same time, migration disrupts aging careers' social
      citizenship both in Bulgaria and in Spain by limiting or even excluding them from
      state welfare support. I argue that these two lines of transformation, kinship
      and citizenship, result in new forms of gender and intergenerational
      inequalities. Furthermore, their intersection leads to a move from welfare to
      kinfare, which not only affects present arrangements between migrants, but also
      entails future insecurities.

PMID- 22611576
TI  - Care of older people in migration contexts: local and transnational arrangements
      between Peru and Spain.
AB  - Care arrangements for the elderly are becoming a main social process in
      contemporary societies due to socio-political and lifestyle changes over the last
      few decades. The family and the State play a basic role in the construction of
      care systems and in the establishment of strategies to access care resources. In
      the present context of migration, these resources interact at a transnational
      level, challenging family and State migratory regimes. These new realities need
      the recognition of basic international social rights, as the experiences of
      Peruvians living in a migration context in Spain show.

PMID- 22611577
TI  - Rethinking care through social reproduction: articulating circuits of migration.
AB  - Care has come to dominate much feminist research on globalized migrations and the
      transfer of labor from the South to the North, while the older concept of
      reproduction had been pushed into the background but is now becoming the subject
      of debates on the commodification of care in the household and changes in welfare
      state policies. This article argues that we could achieve a better understanding
      of the different modalities and trajectories of care in the reproduction of
      individuals, families, and communities, both of migrant and nonmigrant
      populations by articulating the diverse circuits of migration, in particular that
      of labor and the family. In doing this, I go back to the earlier North American
      writing on racialized minorities and migrants and stratified social reproduction.
      I also explore insights from current Asian studies of gendered circuits of
      migration connecting labor and marriage migrations as well as the notion of
      global householding that highlights the gender politics of social reproduction
      operating within and beyond households in institutional and welfare
      architectures. In contrast to Asia, there has relatively been little exploration
      in European studies of the articulation of labor and family migrations through
      the lens of social reproduction. However, connecting the different types of
      migration enables us to achieve a more complex understanding of care trajectories
      and their contribution to social reproduction.

PMID- 22611578
TI  - "To rid oneself of the uninvited guest": Robert Koch, Sergei Winogradsky and
      competing styles of practice in medical microbiology.
AB  - Does an infectious disease have one, singular pathogenic cause, or many
      interacting causes? In the discipline of medical microbiology, there is no
      definitive theoretical answer to this question: there, the conditions of
      aetiological possibility exist in a curious tension. Ever since the late 19th
      century, the "germ theory of disease"-"one disease, one cause"- has co-existed
      with a much less well known theory of "multifactorality"-"one disease, many
      interacting causes". And yet, in practice, it is always a singular and never a
      multifactorial aetiology that emerges once the pathogenic world is brought into
      the field of medical perception. This paper seeks to understand why. Performing a
      detailed, genealogical reading of the 2003 severe acute respiratory syndrome
      (SARS) outbreak, it foregrounds a set of links that connect the practical
      diagnostic tools at work within contemporary, 21st century laboratories to the
      philosophical assumptions at work within late-19th century understandings of the
      "germ theory of disease".

PMID- 22611579
TI  - The medicalization of sunlight in the early twentieth century.
AB  - This paper traces the emergence of the therapeutic use of sunlight in medicine
      during the first half of the twentieth century. This was a period of considerable
      flux in medicine with various strands of practice and theory competing. Drawing
      on two case studies of sunlight therapy, both artificial (actinotherapy) and
      natural (heliotherapy), in the treatment of rickets and tuberculosis this paper
      will explore how medicine was constituted within these regimes. The paper will
      argue that therapeutic and clinical applications of sunlight helped establish an
      association between sunlight and health but also defined a particular and
      specific performance of medicine.

PMID- 22611580
TI  - A special kind of married man: notions of marriage and married men in the Swedish
      gay press, 1954-1986.
AB  - There has long been ambivalence in the LGBT movement and related research as to
      the meaning of gay identity in relation to marriage. The article explores
      changing homonormative discourses of marriage and married men within the Swedish
      gay press from the mid 1950s to the mid 1980s. Expressions of the changes are a
      shift in language and in views of extramarital relationships, openness, and gay
      male identity. As a result of the shift, "married men," including both "married
      homosexuals" and "bisexuals," came to be distinguished from "gays."

PMID- 22611581
TI  - Outdoor brothel culture: the un/making of a transsexual stroll in Vancouver's
      West End, 1975-1984.
AB  - In the mid-1970s, following a series of police raids on prostitution inside
      downtown nightclubs, a community of approximately 200 sex workers moved into
      Vancouver's West End neighborhood, where a small stroll had operated since the
      early 1970s. This paper examines the contributions made by three male-to-female
      (MTF) transsexuals of color to the culture of on-street prostitution in the West
      End. The trans women's stories address themes of fashion, working conditions,
      money, community formation, violence, and resistance to well-organized anti
      prostitution forces. These recollections enable me to bridge and enrich trans
      history and prostitution history - two fields of inquiry that have under
      represented the participation of trans women in the sex industry across the urban
      West. Acutely familiar with the hazards inherent in a criminalized, stigmatized
      trade, trans sex workers in the West End manufactured efficacious strategies of
      harm reduction, income generation, safety planning, and community building.
      Eschewing the label of "victim", they leveraged their physical size and style,
      charisma, contempt towards pimps, earning capacity, and seniority as the first
      workers on the stroll to assume leadership within the broader constituency of
      "hookers on Davie Street". I discover that their short-lived outdoor brothel
      culture offered only a temporary bulwark against the inevitability of eviction
      via legal injunction in July 1984, and the subsequent rise in lethal violence
      against all prostitutes in Vancouver, including MTF transsexuals.

PMID- 22611582
TI  - The plague under Commodus as an unintended consequence of Roman grain market
      regulation.
AB  - This paper begins with a review of Roman grain market policies. It is argued that
      policies such as forced sales and maximum prices made urban consumers hesitant to
      rely on the market for secure access to grain. Consequently, consumers hoarded
      grain in their homes. The hoarded grain formed a volatile fuel ready to be
      ignited by the arrival of the bubonic plague bacillus. This scenario fits events
      in the city of Rome under Commodus. Attested grain market interventions were
      followed by a severe epidemic, arguably bubonic plague, which decimated the
      city's population.

PMID- 22611583
TI  - Self-sale and voluntary entry into unfreedom, 300-1100.
AB  - Voluntary entry into unfreedom in late antiquity and the early middle ages has
      tended to be interpreted as anything but voluntary: instead, self-sales and
      autodeditions have been seen mostly in terms of coercion, whether by force or by
      necessity, and associated with particular moments of social crisis. This article
      argues that the sensitive nature of the topic resulted in an exceptionally
      misleading representation of self-sales in the legal and literary sources, albeit
      in divergent ways. Roman and Byzantine law treated self-sale as illegal, while at
      the same time leaving room for manoeuvre in practice, and took a very judgmental
      view of self-sellers. Early Christian sources, on the contrary, took them as
      emblematic of the oppression of the poor, and harnessed them for political
      admonishment, presenting self-sellers as passive victims of rapacious buyers and
      bad governance. While diametrically different in their presentation of the moral
      significance of self-sales, law and literary sources both therefore contribute to
      the impression that the distinction between free and unfree was the most
      important social divide. Documentary sources, by contrast, present a very
      different picture, suggesting a higher degree of continuity (and perhaps
      frequency) in this practice, but also that it could be the object of active and
      careful negotiation and bargaining, with people in different social and economic
      circumstances using free status as an asset for a variety of purposes and in a
      very instrumental way, far removed in its concerns from the elite discourse which
      took freedom as an essential value.

PMID- 22611584
TI  - "The law has no feeling for poor folks like us!" Everyday responses to legal
      compulsion in England's working-class communities, 1871-1904.
AB  - During the late Victorian period, the role of the state increased dramatically in
      England's working-class urban communities. New laws on labor, health, and
      education, enforced by a growing bureaucracy of elected and appointed officials,
      extended the reach of public authority into daily life on an unprecedented scale.
      Everyday negotiations between these officials and working-class men and women, I
      argue, were key moments for determining the practical impact of new social
      welfare policies. This was particularly true in the contestation over children's
      compulsory school attendance, as I demonstrate through a close examination of the
      daily encounters between parents and education officials. Despite the growing
      size and authority of the Victorian state, working-class parents effectively
      mitigated the impact of the compulsory education laws on their families. They
      were able to do so because the categories that governed the level of enforcement
      age, household economic status, health, and labor-were themselves determined
      through daily dialogues between parents and education officials. Parents'
      familiarity with the law and with the dynamics of the public education
      bureaucracy were key factors in these negotiations, as were internal fractures
      within the Victorian state itself. Working-class parents, and mothers in
      particular, also countered officials' moral policy justifications with their own
      discourse of right and wrong, which focused on the legitimacy of parental
      authority, an insistence on just treatment, and the elevation of household needs
      over the laws' requirements.

PMID- 22611585
TI  - The "Quadroon-Placage" myth of antebellum New Orleans: Anglo-American
      (mis)interpretations of a French-Caribbean phenomenon.
AB  - The intimate relationships between white men and women of color in antebellum New
      Orleans, commonly known by the term placage, are a large part of the romanticized
      lore of the city and its history. This article exposes the common understanding
      of placage as myth. First, it reveals the source of the myth in a collection of
      accounts by travelers to the city in the decades leading up to the Civil War.
      Next, it uses a database of information on hundreds of white male-colored female
      relationships during the period to provide a more accurate account of the people
      in and nature of these relationships. Finally, it explains the purpose served by
      the myth by identifying three traditions that shaped its development: the culture
      of Southern Honor, the Anti-Slavery movement, and the bon-ton tradition of
      Georgian England. In a broader sense, this paper shows how myths are created and
      perpetuated, the temptations and dangers of uncritically accepting them, and the
      value to understanding their creation.

PMID- 22611586
TI  - Tourism and the Hispanicization of race in Jim Crow Miami, 1945-1965.
AB  - This article examines how Miami's significant presence of Anglo Caribbean blacks
      and Spanish-speaking tourists critically influenced the evolution of race
      relations before and after the watershed 1959 Cuban Revolution. The convergence
      of people from the American South and North, the Caribbean, and Latin America
      created a border culture in a city where the influx of Bahamian blacks and
      Spanish-speakers, especially tourists, had begun to alter the racial landscape.
      To be sure, Miami had many parallels with other parts of the South in regard to
      how blackness was understood and enforced by whites during the first half of the
      twentieth century. However, I argue that the city's post-WWII meteoric tourist
      growth, along with its emergence as a burgeoning Pan-American metropolis,
      complicated the traditional southern black-white dichotomy. The purchasing power
      of Spanish-speaking visitors during the postwar era transformed a tourist economy
      that had traditionally catered to primarily wealthy white transplanted
      Northerners. This significant change to the city's tourist industry significantly
      influenced white civic leaders' decision to occasionally modify Jim Crow
      practices for Latin American vacationers. In effect, Miami's early Latinization
      had a profound impact on the established racial order as speaking Spanish became
      a form of currency that benefited Spanish-speaking tourists-even those of African
      descent. Paradoxically, this ostensibly peculiar racial climate aided the local
      struggle by highlighting the idiosyncrasies of Jim Crow while perpetuating the
      second-class status of native-born blacks.

PMID- 22611587
TI  - Shutt up: bubonic plague and quarantine in early modern England.
AB  - The outbreak of bubonic plague that struck London and Westminster in 1636
      provoked the usual frenzied response to epidemics, including popular flight and
      government-mandated quarantine. The government asserted that plague control
      measures were acts of public health for the benefit of all. However, contrary to
      this government narrative of disease prevention there was a popular account that
      portrayed quarantine and isolation as personal punishment rather than prudent
      policy. In examining the 1636 outbreak on the parish as well as the individual
      level, reasons for this inconsistency between official and unofficial
      perspectives emerge. Quarantine and its effects were not classless, and its
      implementation was not always strictly in the name of public health. Government
      application of quarantine was remarkably effective, but it could never be
      uncontroversial both because of circumstances and because of misuse. The flight
      of the wealthiest from London and Westminster left only the more socially
      vulnerable to be quarantined. Though plague policy was financially sensitive to
      the poorest, it was costly to the middling sort. Another cause of controversy was
      the government's use of quarantine as a punishment to control individuals found
      breaking other laws. Though not widely publicized, popular narratives continually
      included grievances about the cruelty and inequity of quarantine and the
      militaristic nature of its implementation. Despite these objections, quarantine
      remained a staple of the government response to plague outbreaks throughout the
      seventeenth century.

PMID- 22611588
TI  - 55% of hospitals are affiliated with a health care system.

PMID- 22611589
TI  - The lead time distribution when lifetime is subject to competing risks in cancer
      screening.
AB  - This paper extends the previous probability model for the distribution of lead
      time in periodic cancer screening exams, namely, in that the lifetime T is
      treated as a random variable, instead of a fixed value. Hence the number of
      screens for a given individual is a random variable as well. We use the actuarial
      life table from the Social Security Administration to obtain the lifetime
      distribution, and then use this information to project the lead time distribution
      for someone with a future screening schedule. Simulation studies using the HIP
      study group data provide estimates of the lead time under different screening
      frequencies. The projected lead time has two components: a point mass at zero
      (corresponding to interval cases detected between screening exams) and a
      continuous probability density. We present estimates of the projected lead time
      for participants in a breast cancer screening program. The model is more
      realistic and can inform optimal screening frequency. This study focuses on
      breast cancer screening, but is applicable to other kinds of cancer screening
      also.

PMID- 22611590
TI  - A smooth ROC curve estimator based on log-concave density estimates.
AB  - We introduce a new smooth estimator of the ROC curve based on log-concave density
      estimates of the constituent distributions. We show that our estimate is
      asymptotically equivalent to the empirical ROC curve if the underlying densities
      are in fact log-concave. In addition, we empirically show that our proposed
      estimator exhibits an efficiency gain for finite sample sizes with respect to the
      standard empirical estimate in various scenarios and that it is only slightly
      less efficient, if at all, compared to the fully parametric binormal estimate in
      case the underlying distributions are normal. The estimator is also quite robust
      against modest deviations from the logconcavity assumption. We show that
      bootstrap confidence intervals for the value of the ROC curve at a fixed false
      positive fraction based on the new estimate are on average shorter compared to
      the approach by Zhou and Qin (2005), while maintaining coverage probability.
      Computation of our proposed estimate uses the R package logcondens that
      implements univariate log-concave density estimation and can be done very
      efficiently using only one line of code. These obtained results lead us to
      advocate our estimate for a wide range of scenarios.

PMID- 22611591
TI  - Targeted minimum loss based estimation of causal effects of multiple time point
      interventions.
AB  - We consider estimation of the effect of a multiple time point intervention on an
      outcome of interest, where the intervention nodes are subject to time-dependent
      confounding by intermediate covariates. In previous work van der Laan (2010) and
      Stitelman and van der Laan (2011a) developed and implemented a closed form
      targeted maximum likelihood estimator (TMLE) relying on the log-likelihood loss
      function, and demonstrated important gains relative to inverse probability of
      treatment weighted estimators and estimating equation based estimators. This TMLE
      relies on an initial estimator of the entire probability distribution of the
      longitudinal data structure. To enhance the finite sample performance of the TMLE
      of the target parameter it is of interest to select the smallest possible
      relevant part of the data generating distribution, which is estimated and updated
      by TMLE. Inspired by this goal, we develop a new closed form TMLE of an
      intervention specific mean outcome based on general longitudinal data structures.
      The target parameter is represented as an iterative sequence of conditional
      expectations of the outcome of interest. This collection of conditional means
      represents the relevant part, which is estimated and updated using the general
      TMLE algorithm. We also develop this new TMLE for other causal parameters, such
      as parameters defined by working marginal structural models. The theoretical
      properties of the TMLE are also practically demonstrated with a small scale
      simulation study.The proposed TMLE is building upon a previously proposed
      estimator Bang and Robins (2005) by integrating some of its key and innovative
      ideas into the TMLE framework.

PMID- 22611592
TI  - A refreshing account of principal stratification.
AB  - Pearl (2011) invites researchers to contribute to a discussion on the logic and
      utility of principal stratification in causal inference, raising some thought
      provoking questions. In our commentary, we discuss the role of principal
      stratification in causal inference, describing why we view the principal
      stratification framework as useful for addressing causal inference problems where
      causal estimands are defined in terms of intermediate outcomes. We focus on
      mediation analysis and principal stratification analysis, showing that they
      generally involve different causal estimands and answer different questions. We
      argue that even when principal stratification may not answer the causal questions
      of primary interest, it can be a preliminary analysis of the data to assess the
      plausibility of identifying assumptions. We also discuss the use of principal
      stratification to address issues of surrogate outcomes. Our discussion stresses
      that a principal stratification analysis should account for all the principal
      strata and evaluate the distributions of potential outcomes in each of the
      principal strata. To this end, we view a Bayesian analysis particularly suited
      for drawing inference on principal strata membership and principal strata
      effects.

PMID- 22611593
TI  - Exploring multicollinearity using a random matrix theory approach.
AB  - Clustering of gene expression data is often done with the latent aim of dimension
      reduction, by finding groups of genes that have a common response to potentially
      unknown stimuli. However, what is poorly understood to date is the behaviour of a
      low dimensional signal embedded in high dimensions. This paper introduces a
      multicollinear model which is based on random matrix theory results, and shows
      potential for the characterisation of a gene cluster's correlation matrix. This
      model projects a one dimensional signal into many dimensions and is based on the
      spiked covariance model, but rather characterises the behaviour of the
      corresponding correlation matrix. The eigenspectrum of the correlation matrix is
      empirically examined by simulation, under the addition of noise to the original
      signal. The simulation results are then used to propose a dimension estimation
      procedure of clusters from data. Moreover, the simulation results warn against
      considering pairwise correlations in isolation, as the model provides a mechanism
      whereby a pair of genes with 'low' correlation may simply be due to the
      interaction of high dimension and noise. Instead, collective information about
      all the variables is given by the eigenspectrum.

PMID- 22611594
TI  - The Beta-Binomial SGoF method for multiple  dependent tests.
AB  - In this paper a correction of SGoF multitesting method for dependent tests is
      introduced. The correction is based in the beta-binomial model, and therefore the
      new method is called Beta- Binomial SGoF (or BB-SGoF). Main properties of the new
      method are established, and its practical implementation is discussed. BB-SGoF is
      illustrated through the analysis of two different real data sets on gene/protein
      expression levels. The performance of the method is investigated through
      simulations too. One of the main conclusions of the paper is that SGoF strategy
      may have much power even in the presence of possible dependences among the tests.

PMID- 22611595
TI  - Detecting sample misidentifications in genetic association studies.
AB  - Genetic association studies require that the genotype data from a given person
      can be correctly linked to the phenotype data from the same person. However,
      sample misidentification errors sometimes happen, whereby the link becomes
      invalid for some of the subjects in a study. This can have substantial
      consequences in terms of power to detect truly associated variants. In family
      based studies, Mendelian inconsistencies can be used to detect sample
      misidentification. Genome-wide association studies (GWAS), however, typically use
      unrelated individuals, making error detection more problematic. Here we present a
      method for identifying potential sample misidentifications in GWAS and other
      genetic association studies building on ideas from forensic sciences. A widely
      used ad-hoc method for error detection is to check if the sex of an individual
      matches its X-linked genotype. We generalize this idea to less stringent
      associations between known genotypes and phenotypes, and show that if several
      known associations are combined, the power to detect misidentifications increases
      substantially. Individuals with an unlikely set of phenotypes given their
      genotypes are flagged as potential errors. We provide analytical and simulation
      results comparing the odds that the genotype and phenotype are both from the same
      individual for different numbers of available genotype-p henotype associations
      and for different information content of the associations. Our method has good
      sensitivity and specificity with as few as ten moderately informative genotype
      phenotype associations. We apply the method to GWAS data from the Danish National
      Birth Cohort.

PMID- 22611596
TI  - Achieving better quality of care for low-income populations: the roles of health
      insurance and the medical home in reducing health inequities.
AB  - In the United States, uninsured and low-income adults experience substantial
      health and health care inequities when compared with insured and higher-income
      individuals. A new analysis of the Commonwealth Fund 2010 Biennial Health
      Insurance Survey demonstrates that when low-income adults have both health
      insurance and a medical home, they are less likely to report cost-related access
      problems, more likely to be up-to-date with preventive screenings, and report
      greater satisfaction with the quality of their care. Moreover, the gaps in health
      care between them and higher-income populations are significantly reduced. The
      Affordable Care Act includes numerous provisions that will significantly expand
      health insurance coverage, especially to low-income patients, as well as
      provisions to promote medical homes. Along with supporting the full
      implementation of coverage expansions, it will be important for public and
      private stakeholders to create opportunities that enhance access to medical homes
      for vulnerable populations.

PMID- 22611597
TI  - Borrowing information across genes and experiments for improved error variance
      estimation in microarray data analysis.
AB  - Statistical inference for microarray experiments usually involves the estimation
      of error variance for each gene. Because the sample size available for each gene
      is often low, the usual unbiased estimator of the error variance can be
      unreliable. Shrinkage methods, including empirical Bayes approaches that borrow
      information across genes to produce more stable estimates, have been developed in
      recent years. Because the same microarray platform is often used for at least
      several experiments to study similar biological systems, there is an opportunity
      to improve variance estimation further by borrowing information not only across
      genes but also across experiments. We propose a lognormal model for error
      variances that involves random gene effects and random experiment effects. Based
      on the model, we develop an empirical Bayes estimator of the error variance for
      each combination of gene and experiment and call this estimator BAGE because
      information is Borrowed Across Genes and Experiments. A permutation strategy is
      used to make inference about the differential expression status of each gene.
      Simulation studies with data generated from different probability models and real
      microarray data show that our method outperforms existing approaches.

PMID- 22611598
TI  - Hierarchical Bayes model for predicting effectiveness of HIV combination
      therapies.
AB  - HIV patients are treated by administration of combinations of antiretroviral
      drugs. The very large number of such combinations makes the manual search for an
      effective therapy practically impossible, especially in advanced stages of the
      disease. Therapy selection can be supported by statistical methods that predict
      the outcomes of candidate therapies. However, these methods are based on clinical
      data sets that have highly unbalanced therapy representation. This paper presents
      a novel approach that considers each drug belonging to a target combination
      therapy as a separate task in a multi-task hierarchical Bayes setting. The drug
      specific models take into account information on all therapies containing the
      drug, not just the target therapy. In this way, we can circumvent the problem of
      data sparseness pertaining to some target therapies. The computational validation
      shows that compared to the most commonly used approach that provides therapy
      information in the form of input features, our model has significantly higher
      predictive power for therapies with very few training samples and is at least as
      powerful for abundant therapies.

PMID- 22611599
TI  - The practical effect of batch on genomic  prediction.
AB  - Measurements from microarrays and other high-throughput technologies are
      susceptible to non-biological artifacts like batch effects. It is known that
      batch effects can alter or obscure the set of significant results and biological
      conclusions in high-throughput studies. Here we examine the impact of batch
      effects on predictors built from genomic technologies. To investigate batch
      effects, we collected publicly available gene expression measurements with known
      outcomes, and estimated batches using date. Using these data we show (1) the
      impact of batch effects on prediction depends on the correlation between outcome
      and batch in the training data, and (2) removing expression measurements most
      affected by batch before building predictors may improve the accuracy of those
      predictors. These results suggest that (1) training sets should be designed to
      minimize correlation between batches and outcome, and (2) methods for identifying
      batch-affected probes should be developed to improve prediction results for
      studies with high correlation between batches and outcome.

PMID- 22611600
TI  - Abstracts of the TERMIS EU 2011 Annual Meeting, Tissue Engineering & Regenerative
      Medicine International Society, 7-11 June, 2011, Granada, Spain.

PMID- 22611601
TI  - [Musculoskeletal tumor].

PMID- 22611602
TI  - Searching for hope.

PMID- 22611603
TI  - Stem cell tourism and Canadian family physicians.

PMID- 22611604
TI  - Controlling pain and reducing misuse of opioids:  ethical considerations.
AB  - OBJECTIVE: To help family physicians achieve an ethical balance in their opioid
      prescribing practices. QUALITY OF EVIDENCE: MEDLINE was searched for English
      language articles published between 1985 and 2011. Most available evidence was
      level III. MAIN MESSAGE: It is essential to follow practice guidelines when
      prescribing opioids, except when another course of action is demonstrably
      justified. In addition, when considering the appropriateness of an opioid
      prescription, with its many ethical implications, the decision can be usefully
      guided by the application of the ethical principles of beneficence,
      nonmaleficence, respect for autonomy, and justice. As well, it is essential to
      keep current about legal and regulatory changes and provincial electronic
      registries of opioid prescriptions. CONCLUSION: Physicians need to ensure that
      their patients' pain is properly assessed and managed. Reaching optimal pain
      control might necessitate prescribing opioids. But the obligation to provide pain
      relief needs to be balanced with an equally important responsibility not to
      expose patients to risk of addiction and not to create opportunities for drug
      diversion, trafficking, and the addiction of others. Basic ethical principles can
      provide a framework to help physicians make ethically appropriate decisions about
      opioid prescribing.

PMID- 22611605
TI  - Managing cardiometabolic risk in primary care: summary of the 2011 consensus
      statement.

PMID- 22611606
TI  - Can nicotine use alleviate symptoms of psoriasis?

PMID- 22611607
TI  - Training in interprofessional collaboration:  pedagogic innovation in family
      medicine units.
AB  - PROBLEM ADDRESSED: A number of agencies that accredit university health sciences
      programs recently added standards for the acquisition of knowledge and skills
      with respect to interprofessional collaboration. Within primary care settings
      there are no practical training programs that allow students from different
      disciplines to develop competencies in this area. OBJECTIVE OF THE PROGRAM: The
      training program was developed within family medicine units affiliated with
      Universite Laval in Quebec for family medicine residents and trainees from
      various disciplines to develop competencies in patient-centred, interprofessional
      collaborative practice in primary care. PROGRAM DESCRIPTION: Based on adult
      learning theories, the program was divided into 3 phases--preparing family
      medicine unit professionals, training preceptors, and training the residents and
      trainees. The program's pedagogic strategies allowed participants to learn with,
      from, and about one another while preparing them to engage in contemporary
      primary care practices. A combination of quantitative and qualitative methods was
      used to evaluate the implementation process and the immediate results of the
      training program. CONCLUSION: The training program had a positive effect on both
      the clinical settings and the students. Preparation of clinical settings is an
      important issue that must be considered when planning practical interprofessional
      training.

PMID- 22611608
TI  - Prescription opioid use and misuse: piloting an educational strategy for rural
      primary care physicians.
AB  - OBJECTIVE: To evaluate the feasibility and effectiveness of a multifaceted
      educational intervention to improve the opioid prescribing practices of rural
      family physicians in a remote First Nations community. DESIGN: Prospective cohort
      study. SETTING: Sioux Lookout, Ont. PARTICIPANTS: Family physicians.
      INTERVENTIONS: Eighteen family physicians participated in a 1-year study of a
      series of educational interventions on safe opioid prescribing. Interventions
      included a main workshop with a lecture and interactive case discussions, an
      online chat room, video case conferencing, and consultant support. MAIN OUTCOME
      MEASURES: Responses to questionnaires at baseline and after 1 year on knowledge,
      attitudes, and practices related to opioid prescribing. RESULTS: The main
      workshop was feasible and was well received by primary care physicians in remote
      communities. At 1 year, physicians were less concerned about getting patients
      addicted to opioids and more comfortable with opioid dosing. CONCLUSION:
      Multifaceted education and consultant support might play an important role in
      improving family physician comfort with opioid prescribing, and could improve the
      treatment of chronic pain while minimizing the risk of addiction.

PMID- 22611609
TI  - Why are response rates in  clinician surveys declining?
AB  - OBJECTIVE: To understand why response rates in clinician surveys are declining.
      DESIGN: Cross-sectional fax-back survey. SETTING: British Columbia. PARTICIPANTS:
      Random sample of family physicians and all gynecologists in the College of
      Physicians and Surgeons of British Columbia's registry. MAIN OUTCOME MEASURES:
      Accuracy of the College of Physicians and Surgeons of British Columbia's
      registry, and the prevalence and characteristics of physicians with policies not
      to participate in any surveys. RESULTS: Of 542 physicians who received surveys,
      76 (14.0%) responded. On follow-up we found the following: the College of
      Physicians and Surgeons of British Columbia's registry was inaccurate for 94
      (17.3%) listings; 14 (2.6%) physicians were away; 100 (18.5%) were not eligible;
      and 197 (36.3%) had an office policy not to participate in any surveys. Compared
      with the respondents, physicians with an office policy not to participate in any
      surveys were more likely to be men, less likely to be white, more likely to have
      urban-based practices, and more likely to have been in practice for more than 15
      years. CONCLUSION: Many physicians have an office policy not to participate in
      any surveys. Owing to the trend of lower response rates, recommendations of
      minimum response rates for clinician surveys by many journals might need to be
      reassessed.

PMID- 22611610
TI  - Awareness of do-not-resuscitate orders: what do patients know and want?
AB  - OBJECTIVE: To assess outpatient understanding of and previous experiences with do
      not-resuscitate (DNR) orders and to gauge patient preferences with respect to DNR
      discussions. DESIGN: Cross-sectional, self-administered survey. SETTING: Four
      urban primary care physician offices in Vancouver, BC. PARTICIPANTS: A total of
      429 consecutive patients 40 years of age and older presenting for routine primary
      care between March and May 2009. MAIN OUTCOME MEASURES: Awareness of, knowledge
      about, and experiences with DNR decisions; when, where, and with whom patients
      wished to discuss DNR decisions; and differences in responses by sex, age, and
      ethnicity, assessed using chi2 tests of independence. RESULTS: The response rate
      was 90%, with 386 of 429 patients completing the surveys. Most (84%) respondents
      had heard of the terms do not resuscitate or DNR. Eighty-six percent chose family
      physicians as among the people they most preferred to discuss DNR decisions with;
      56% believed that initial DNR discussions should occur while they were healthy;
      and 46% thought the discussion should take place in the office setting. Of those
      who were previously aware of DNR orders, 70% had contemplated DNR for their own
      care, with those older than 60 years more likely to have done so (P = .02);
      however, only 8% of respondents who were aware of DNR orders had ever discussed
      the subject with a health care provider. Few patients (16%) found this topic
      stressful. CONCLUSION: Most respondents were well informed about the meaning of
      DNR, thought DNR discussions should take place when patients were still healthy,
      preferred to discuss DNR decisions with family physicians, and did not consider
      the topic stressful. Yet few respondents reported having had a conversation about
      DNR decisions with any health care provider. Disparity between patient
      preferences and experiences suggests that family physicians can and should
      initiate DNR discussions with younger and healthier patients.

PMID- 22611611
TI  - Estimating patient demographic profiles from practice location.
AB  - OBJECTIVE: To test the accuracy of imputing a practice population's average
      socioeconomic characteristics (such as average education levels and average
      income) using census data centred on the location of the practice. DESIGN:
      Comparison of census data with survey data collected in primary care offices.
      SETTING: Ontario. PARTICIPANTS: A cross-sectional sample of patients from 116
      urban practices. MAIN OUTCOME MEASURES: Patient data were compared with census
      data at different levels of aggregation using mean absolute relative error (ARE),
      median ARE, and Spearman rank correlations. RESULTS: A total of 4413 patient
      surveys were collected. Differences between patient profiles and census data were
      large. Most mean AREs were clustered between 0.70 and 0.80, and median AREs were
      as high as 1.67. Correlations were low (rho = 0.02) to moderate (rho = 0.48).
      These results held across both levels of aggregation. CONCLUSION: The use of
      imputation techniques based on practice location is inadvisable, given the large
      differences that were observed.

PMID- 22611612
TI  - Rural Rx: a program developed in New Mexico may change how health care is
      delivered in rural America.

PMID- 22611613
TI  - A medical neighborhood: accountable care organizations could solve some of health
      care's biggest problems, but they're largely untested.

PMID- 22611614
TI  - [Theoretical and practical considerations in rational polytherapy for epilepsy].
AB  - Author analyses the consideration of rational polytherapy for epilepsy. Among the
      theoretical aspects he points the different effect of seizure inhibitory drugs on
      the epilepsy models but didn't find data enough for the basis of any successful
      combination. Combinations of compounds having different way of action are more
      promising. Rational polytherapy can serve also the epileptic patients' tailored
      therapy in the daily routine. There have already been some proved synergisms
      concerning drug interactions. Based on detailed analysis of side effects a
      possibility occurs for neutralization of side effects when anticonvulsants with
      side effects of opposite nature are combined. Considering both the side effect
      profiles and the different (somatic and psychic) habits of the patients we can
      create a special list of favourable combinations. Co-morbid states and their
      treatments play a significant role in the application of rational polytherapy.
      Combination of anticonvulsants of lower potential but without drug-interactions
      can be the choice in these cases. The non-epileptic indications of the
      anticonvulsants can also be utilized in polymorbid patients. Based on the
      theoretical and practical considerations the author defines the ten-step
      cognitive-preparation-process in planning the optimal (poly)therapy. On
      speculative basis he suggests eight beneficial versions of seizure inhibitory
      rational polytherapy.

PMID- 22611615
TI  - [The carrier model of neurology in Hungary: a proposal for the solution until
      2020].
AB  - Based on our previous survey on the capacities of neurological services and on
      the predictable changes in the neurologist workforce in Hungary, we present a
      proposal for the organization of the structure of neurological services in the
      future. We discuss the diagnostic groups treated by neurologists, the
      neurological services and their progressive organization. Using the current
      capacities as baseline, we propose patient groups to be treated by neurologists
      in the future, and the levels of services. Based on the tendencies seen in the
      last years we suggest to consider to allocate acute stroke services exclusively
      to stroke units in neurological departments, and we identify a few other
      diagnostic groups where neurology should have a larger share in patient care. We
      define three levels for inpatient care: university departments, regional/county
      hospitals, city hospitals. Instead of minimum criteria we assign outpatient and
      inpatient standards that are functional from the economic point of view as well.
      University departments cover all areas of neurological services, have a function
      in graduate and postgraduate training, and on a regional basis they participate
      in professional quality assurance activities at the county and city hospital
      levels, and would have a more independent role in residency training. As far as
      patient care is concerned, the task of the regional/county hospitals would be
      similar to that of university departments - without the exclusively university
      functions. A general neurological service would be offered at the city hospital
      level - the representation of all subspecialties of neurology is not required.
      Neurorehabilitation would be organized at special units of neurological wards at
      the city hospital level, at independent neurorehabilitation wards in
      regional/county hospitals, and also as an outpatient service offered at the
      patients' home. The most significant organizational change would affect the
      outpatient neurological services. In addition to the special outpatient units
      associated with university departments and regional/county hospitals, the general
      neurological outpatient services would be organized as private practices,
      similarly to the current system of general practitioners, where the individual
      practices contract independently with the health insurance fund. Their task would
      be a general neurological service offered 30 hours per week, and also basic,
      screening neurophysiological and neurosonological examinations, with proper
      equipment and trained assistance. A transformation in residency training and a
      change in financing is needed for this plan to fulfill.

PMID- 22611616
TI  - [Vascular or "lower body Parkinsonism": rise and fall of a diagnosis].
AB  - The "arteriosclerotic parkinsonism", which is called vascular parkinsonism (VP),
      was first described by Critchley'. The broad based slow gait, reduced stride
      lenght, start hesitation, freezing and paratonia was mentioned as "lower body
      parkinsonism" (LBP) which can be associated by slow speech, dysexecutive
      syndrome, and hand tremor of predominantly postural character. In VP the DAT-scan
      proved normal dopamine content of the striatum in contrast with Parkinson's
      disease (PD). Additionally, Lewy bodies of brainstem type were not found in VR
      Probability of VP increases if central type pathologic gait is prominent; the
      hands are slightly involved, the MRI indicates transparent periventricular white
      substance and/or brain atrophy. In some cases differentiation of gait apraxia and
      parkinsonism could be challenging. There is no rigor of the lower limbs at rest
      in neither of them, the disturbance of movement is evoked by the gait itself.
      Three subtypes of "gait ignition failure" has been recently described: (1)
      ignition apraxia, (2) equilibrium apraxia and (3) mixed gait apraxia. The primary
      progressive freesing gait was considered as a Parkinson-plus syndrome. Freesing
      occurs more frequently in diseases with pakinsonism than in PD. The grade of
      ventricle dilatation and the frontal leukoaraiosis was similar in LBP and gait
      apraxia. In cases of normal pressure hydrocephalus the impaired gait may mimic
      PD. Pathologic gait in VP can be explained by the lesions of the senso-motor
      association pathways in dorsal paramedian white substance within the vulnerable
      borderzone region. These may be colocalized with the representation of the lower
      extremities in the posterior third of the supplementer motor area. Rektor2
      proposed to change the name of LBP to "cerebrovascular gait disorder".
      Notwithstandig central type gait disorder develops also in many degenerative
      diseases other than cerebro-vascular origin. The neuronal net controling the
      regulation of movement is widespread, therefore several cortical and subcortical
      lesions could elicit large variations of pathologic gait, ie.: ataxia, apraxia,
      ignition failure, akinesis etc. IN CONCLUSION: most of the central gait disorders
      regarding the pathology and their appearance can not be called "parkinsonism";
      these are much closer related to the localization of lesions rather than to the
      diagnostic categories.

PMID- 22611617
TI  - [Subarachnoid hemorrhage in Hungary: analysis based on the 2009 hospital
      reports].
AB  - BACKGROUND AND PURPOSE: We analyzed the statistical characteristics of
      subarachnoid hemorrhage (SAH) in Hungary in 2009. METHODS: Using data supplied by
      the hospitals about their inpatient services to the National Health Insurance
      Fund with ICD-10 code 160. RESULTS: 1403 SAH hospital cases were recorded in 1028
      patients. That is much more than we expected from previous data. 63.6% were
      women, hospital case fatality was 12.2%. The average hospital stay was 6.47 days.
      763 CT examinations were done (74.2% of the patients). Hypertension was recorded
      in 61.3% of the patients. The incidence was increasing with age till the age
      group of 51-60 years, and decreased beyond that. In 531 patients the source of
      bleeding could be verified. Aneurysm of the anterior communicating artery was
      more frequent in men, aneurysm of the middle cerebral artery (MCA) and internal
      carotid artery in women. In total MCA aneurysm was the most frequent.
      Arteriovenous malformation was present in 7.6% of the patients. SAH was most
      frequent in January and February, rarest in April and August. CONCLUSION: SAH is
      more frequent in Hungary than previously thought.

PMID- 22611618
TI  - A8344G mutation of the mitochondrial DNA with typical mitochondrial
      encephalomyopathy with lactic acidosis and stroke-like episodes syndrome.
AB  - We report an unusual case of juvenile ischaemic stroke syndrome associated with
      the A8344G mutation in tRNA(Lys) gene of mitochondrial DNA. The clinical
      phenotype of patient was typical for MELAS (mitochondrial ecephalomyapathy with
      lactate acidosis and stroke like episodes). The MELAS has been related to
      mutation A3243G in most cases, but some other mitochondrial DNA mutations were
      described in the background of this syndrome as well. A 22-years-old man and his
      family were investigated. Throughout clinical investigation as well as Doppler
      sonography, neuroradiological, and immunserological examinations were performed.
      Molecular studies included the analysis of the Leiden, prothrombin G20210A and
      the most common mitochondrial DNA mutations. The DNA analysis of the proband
      revealed a heteroplasmic A8344G substitution in the T-loop of the tRNALYS gene.
      The mutation could not been detected in her mother blood. We can conclude that
      A8344G mutation of the mitochondrial DNA resulted in juvenile ischemic stroke,
      which is associated only rarely to this genetic alteration. In young age onset of
      a stroke-like episode with undetermined etiology the mtDNA alterations always
      have to be excluded.

PMID- 22611619
TI  - Common variable immunodeficiency with coexisting central nervous system
      sarcoidosis: case report and literature review with implications for diagnosis
      and pathogenesis.
AB  - We describe a patient with a history of longstanding primary generalised
      epilepsy, on anticonvulsant therapy, who presented with fever, headache,
      worsening seizures and hallucinations. Among various investigations, the patient
      had high CSF protein and ACE levels, leptomeningeal nodular enhancement on MRI
      brain and non-caseating granulomas in the brain and meninges on the biopsy. The
      patient was diagnosed with neurosarcoidosis. Subsequently, he was found to be
      panhypogammaglobulinaemic and was diagnosed with probable common variable
      immunodeficiency (CVID). The coexistence of common variable immunodeficiency and
      neurosarcoidosis is rare. Typically, non-caseating granulomas in CVID patients
      are localised in the lymphatic tissue and solid organs. To our knowledge, there
      are only five reports of the granulomas of the central nervous system (CNS) in
      CVID. We discuss the diagnostic difficulties in this case and review the
      literature.

PMID- 22611620
TI  - [Complementary therapies--based on principles of evidence based medicine].

PMID- 22611621
TI  - [Report from the 2011 scientific meeting of the Kornyey Society. Part 1].

PMID- 22611622
TI  - [Intestinal microbiome, gastroenteritis caused by Escherichia coli and resistant
      enterobacteriaceae or the Art of living with our intestines].

PMID- 22611623
TI  - [Uncomplicated urinary tract infections: impact of increasing antibiotic
      resistance in the community].
AB  - Uncomplicated urinary tract infections are commonly encountered in primary care
      and frequently lead to empirical antibiotic prescriptions. The development of
      antibiotic resistance in the community explains treatment failures observed with
      commonly-prescribed drugs such as quinolones and co-trimoxazole. This article
      describes the epidemiology of antibiotic resistance among pathogens causing
      uncomplicated urinary tract infections and the consequences in terms of
      recommendations for empirical antibiotic therapy.

PMID- 22611624
TI  - [Epidemiology and clinical implications of carbapenemase-producing bacteria in
      Switzerland].
AB  - The emergence and global dissemination of carbapenemases represents a major
      threat to public health. Switzerland has not been spared; we report a case-series
      of four patients hospitalised in our institution colonised with carbapenemase
      producing bacteria. Infections caused by carbapenemase-producing
      Enterobacteriaceae limit therapeutic options and increase mortality. Detection of
      carbapenemases is also a challenge for laboratories. It is imperative to
      implement stringent infection control measures in order to prevent epidemics at
      the hospital level.

PMID- 22611625
TI  - [Measures against surgical site infections in orthopaedic surgery].
AB  - Orthopaedic surgery has low healthcare-associated infection incidences compared
      to other surgical disciplines. However, whenever they occur, these infections are
      associated with substantial morbidity, prolonged hospital stay, high costs, and
      difficulties of eradication with life-long recurrence risks. Among the many
      measures to prevent orthopaedic surgical site infections, only few are based on
      strong evidence, and there is insufficient evidence to ascertain which element is
      superior to any other. This highlights the need for multimodal approaches
      involving active post-discharge surveillance, as well as measures at every step
      of the care process; from the individual patient to department-wide interventions
      targeting all infections, and including antibiotic stewardship.

PMID- 22611626
TI  - [Antimicrobial agents and renal elimination: towards individual dosage
      adjustment?].
AB  - The efficacy and safety of anti-infective treatments are associated with the drug
      blood concentration profile, which is directly correlated with a dosing
      adjustment to the individual patient's condition. Dosing adjustments to the renal
      function recommended in reference books are often imprecise and infrequently
      applied in clinical practice. The recent generalisation of the KDOQI (Kidney
      Disease Outcome Quality Initiative) staging of chronically impaired renal
      function represents an opportunity to review and refine the dosing
      recommendations in patients with renal insufficiency. The literature has been
      reviewed and compared to a predictive model of the fraction of drug cleared by
      the kidney based on the Dettli's principle. Revised drug dosing recommendations
      integrating these predictive parameters are proposed.

PMID- 22611627
TI  - [Hepatitis B immunization in the neonate and the immunocompromised: time to
      resort to dedicated teams?].
AB  - The hepatitis B virus is likely to induce a severe disease when the infection
      occurs in vulnerable individuals. For that reason, clear recommendations are
      issued that vaccine prevention be offered to the immunocompromised and to the
      infant newly born to a chronically infected mother. However, the vaccine coverage
      is definitely suboptimal among these patients and a fair proportion of them are
      only partially vaccinated. An increase in vaccine coverage is demonstrated in
      several studies involving dedicated nursing or medical teams. The prevention of
      hepatitis B infection in vulnerable patients requires a systemic and punctilious
      approach to such a point that one should consider letting the management of these
      preventive measures to dedicated nursing or medical teams.

PMID- 22611628
TI  - [The challenges of HIV-HCV co-infection].
AB  - HIV and HCV share transmission routes and, for this reason, 25% of HIV patients
      are also infected by HCV, and up to 80% of HIV-positive iv drug users. AIDS
      incidence and mortality are not higher in HCV positive patients, but liver
      morbidity and mortality are increased. Spontaneous clearance of HCV after
      infection is less frequent among HIV positive patients. Liver fibrosis progresses
      faster in HIV-HCV co-infected patients compared to HCV mono-infected, but this
      can be partially slowed down with effective antiretroviral therapy and immune
      restoration. Response to HCV treatment is also weaker among co-infected patients.
      Pharmacological interactions and increased toxicity of antiretroviral drugs and
      anti-HCV drugs are challenging for clinicians, especially if the recently
      approved anti-HCV proteases are used.

PMID- 22611629
TI  - [ST segment elevation-acute myocardial infarction management at the office:
      clopidogrel or aspirin?].

PMID- 22611630
TI  - [FMH, patient care meetings and optimism towards AI].

PMID- 22611631
TI  - [What will you do with your Life expectancy?].

PMID- 22611632
TI  - [Psychiatry according to "late" Felix Gattari].

PMID- 22611633
TI  - [Eradication of persons suffering from trisomies, although they are sweet
      people].

PMID- 22611634
TI  - [Of Age].

PMID- 22611635
TI  - Clinical imaging findings in a girl with Hutchinson-Gilford progeria syndrome.
AB  - We report an 82-year-old girl with premature aging, a karyotype of 46,XX and a de
      novo c.1824C>T mutation encoding p.G608G in the lamin A gene. The clinical
      features of accelerated aging and the molecular finding were consistent with the
      diagnosis of Hutchinson-Gilford progeria syndrome (HGPS). In this presentation,
      we demonstrate the radiological imaging findings of skeletal, oral and
      craniofacial phenotypes of abnormalities associated with HGPS. The oral and
      craniofacial abnormalities caused dental caries, severe malocclusion, and
      swallowing, feeding and speech problems. Dural calcification, and granulation in
      the ear drum and external ear canal were additionally observed.

PMID- 22611636
TI  - A mutation of aspartoacylase gene in a Turkish patient with Canavan disease.
AB  - Canavan disease (CD) is an autosomal recessive inherited disorder characterized
      by spongy degeneration of the brain. The deficiency of aspartoacylase (ASPA),
      resulting in the accumulation of N-acetyl aspartic acid (NAA) in the brain, plays
      an important role in the pathogenesis of the disease. The cardinal features of
      this neurodegenerative disease are macrocephaly, mental retardation, and
      hypotonia. Magnetic resonance imaging (MRI) of the brain generally shows diffuse
      white matter degeneration and also elevated excretion of urinary NAA is usually
      seen. A large number of mutations were identified to date. We report here a 9
      months old girl with Canavan Disease and a homozygous c.79G>A mutation in the
      ASPA gene, detected for the first time in Turkish population.

PMID- 22611637
TI  - A new syndrome: multiple congenital abnormalities and mental retardation in two
      brothers.
AB  - In this report we present two brothers with abnormal neurological development,
      hypotonia, short stature, pylorus stenosis, pectus excavatum, brachycephaly due
      to craniosynostosis, frontal bossing, depressed nasal bridge, high arched-wide
      palate, downslant palpebral fissures, low-set, large ears, thin upper lip and
      bilateral cryptorchidism. The brothers were born to a couple of second cousins
      and were the third and fourth pregnancies of the mother. The father, the mother
      and the eldest sibling were phenotypically and chromosomally normal. The clinical
      findings of the brothers were found to be similar. These clinical findings were
      compared with syndromes showing some of the symptoms, namely Apert, FG, Floating
      Harbor, Shprintzen-Goldberg and Rett Syndromes. However, when the findings were
      detailed, we observed that they did not match completely any of the syndromes in
      a discernable way. The MECP2 gene mutation was analysed because of mental
      retardation, poor neurological evolution and large ears, but no mutation was
      found. So these cases are presented as a new syndrome with apparent autosomal
      recessive inheritance.

PMID- 22611638
TI  - A case of fetal carbamazepine syndrome with right hemihypoplasia of the entire
      body.
AB  - Anticonvulsant drugs taken by pregnant women to prevent seizures are among the
      most common causes of potential harm to the fetus. It has been suggested that
      carbamazepine was less teratogenic than the other drugs. Here, we report a case
      of fetal carbamazepine syndrome presenting with facial dysmorphism, congenital
      heart defect, skeletal abnormalities, renal agenesis, ambiguous genitalia, anal
      atresia, and right hemihypoplasia of the entire body. To the best of our
      knowledge this is the most severe case of fetal carbamazepine syndrome in the
      literature. This case can provide useful data about teratogenicity of
      carbamazepine therapy during the pregnancy.

PMID- 22611639
TI  - A case of Keutel syndrome diagnosed in the neonatal period: associated with
      Binder phenotype.
AB  - Keutel syndrome is a rare autosomal recessive disorder, characterized by
      brachytelephalangia (short, broad distal phalanges), midfacial hypoplasia,
      abnormal cartilage calcifications, peripheral pulmonary stenosis and hearing
      loss. Binder profile is a well known maxillonasal dysplasia composed of midfacial
      hypoplasia with absence of anterior nasal spine and facial dysmophism (short
      nose, flat nasal bridge, perialar flatness, convex upper lip). Here we report a
      Keutel syndrome presenting with Binder phenotype, abnormal calcifications,
      hearing loss and respiratory insufficiency in the newborn period. Keutel syndrome
      should be considered in the differential diagnosis of children with
      tracheobronchial calcifications, midfacial hypoplasia and stippled epiphysis.

PMID- 22611640
TI  - Short-term memory deficits in carrier females with KDM5C mutations.
AB  - We present the cognitive abilities of females from five families who carry a
      mutation in a gene (KDM5C, formerly JARIDIC or SMCX) in Xp 11.2 that encodes a
      transcriptional regulator with histone demethylase activity that is specific for
      dimethylated and trimethylated H3K4. In this report, the cognitive abilities of
      females who carry KDMSC mutations are compared to females who carry mutations in
      other genes known to cause X-linked intellectual and developmental disability
      (XLIDD) conditions. The KDM5C mutation carriers had higher mean scores on the
      abstract/visual and quantitative sections of the Stanford-Binet Intelligence
      Scale: Fourth Edition and lower mean short term memory scores. Implications for
      counseling are presented.

PMID- 22611641
TI  - Clinical and cytogenetic study of a case with familial chromosomal translocation
      presenting with facial dysmorphism and axial neuropathy.
AB  - We report on a 9-year-old female patient presenting with muscle weakness, facial
      dysmorphism and mild mental retardation. She had low birth weight, developmental
      delay, hypotonia and hyporeflexia and difficulties in climbing the stairs. EMG
      revealed axonal polyneuropathy affecting both upper and lower limbs. She was the
      child of non-consanguineous parents, her cytogenetic findings revealed
      46,XX,t(12;14)(q14;q23). The mother's karyotype was normal 46,XX while the
      father's karyotype was 46,XY,t(12;14)(q14;q23) the same as his daughter. Her
      normal sister's karyotype was also 46,XX,t(12; 14) (q14;q23). Fluorescence in
      situ hybridization (FISH) was used to elucidate the breakpoints and Array-CGH was
      done for the patient to confirm the balanced translocation. This observation is
      of interest because it represents a rare case of a balanced translocation with
      abnormal phenotype. Mutant genes causing axonal neuropathy have been located on
      various chromosomes other than 12q14 or 14q24. This report shows the importance
      of molecular cytogenetics and its correlation with abnormal phenotype and the
      possibility of another gene locus at the presently studied chromosomal
      breakpoints. Detailed correlations between chromosome aberrations and their
      phenotypes are of invaluable help in localising genes for axonal polyneuropathy.

PMID- 22611642
TI  - Faciocardiorenal syndrome: a wide clinical spectrum?
AB  - Faciocardiorenal syndrome (FCRS), also named Eastman-Bixler syndrome, is an
      apparent autosomal recessive entity, characterized by endocardial fibroelastosis,
      unusual facial appearance, renal defects and mental retardation. We report a 7
      months male patient, with the diagnosis of endocardial fibroelastosis, an
      abnormal facial appearance (arched eyebrows, broad nasal root, long philtrum and
      microretrognathia) and psychomotor delay. Associated anomalies were:
      plagiocephaly, broad halluces, nail hypoplasia, cryptorchidism, diastasis recti,
      and adducted thumbs. Focal seizures in the mouth were also observed. The
      radiographs revealed advanced bone age and metaphyseal widening of femur and
      tibia. FCRS has an unknown etiology with only three reported cases so far (since
      1977). We report a patient with the main features of FCRS but without the renal
      component, suggesting that this entity can present a wide clinical spectrum.
      Based on these findings and on the few previously reported cases with a highly
      variable phenotype when compared with the original report, we suggest that FCRS
      should be further clinical delineated according to the following leading
      anomalies: endocardial fibroelastosis, unusual facial appearance and mental
      retardation, in order to find more cases that allow a wider clinical description
      and the identification of the genetic defect(s).

PMID- 22611643
TI  - Incontinentia pigmenti with ocular involvement: two cases.
AB  - Incontinentia pigmenti (IP) is a rare, X-linked dominant disorder that presents
      at or soon after birth and presents with cutaneous signs and symptoms. Besides
      its typical skin signs presenting in all patients, central nervous system (CNS),
      ophthalmologic and dental involvement are encountered as well. In this report, we
      present two patients at the verrucous stage of IP and review the literature
      concerning the diagnosis and course of IP.

PMID- 22611644
TI  - Thrombophilia gene mutations in oculoauriculovertebral spectrum.
AB  - Oculoauriculovertebral spectrum or Goldenhar syndrome is a phenotypically and
      probably genetically heterogeneous disorder characterized by hemifacial
      microsomia (unilateral ear abnormalities and ipsilateral mandibular hypoplasia)
      as well as vertebral anomalies and epibulbar dermoid/lipodermoids. Although most
      cases of the Goldenhar syndrome are sporadic, both autosomal recessive and
      dominant inheritance have been reported so far. In this report, we describe the
      clinical aspects of two familial cases with evidence of autosomal dominant
      inheritance and a non-familial case, and compare them with the reports in the
      literature. One of our familial cases was a ten day old female infant of a mother
      with left hemifacial microsomia. She had multiple bilateral preauricular tags and
      a "fleshy masse" on her right cheek. The other familial case was a two months old
      male infant whose father had hemifacial asymmetry. He had unilateral microtia,
      and abnormal antihelix, a skin tag in the contralateral ear associated with
      bilateral sensorineural hearing loss. The third case was a sporadic case who was
      2 years old boy with preauricular skin tag, right hemifacial microsomia and
      limbal dermoid at the temporal limbus of the right eye. As there were no other
      associated defects, the cases we presented here were thought to be mild
      variations of the Goldenhar spectrum. The most commonly encountered mutations of
      thrombophilia genes were studied. We believe that the interfamilial and
      intrafamilial clinical variabilities observed in these cases reinforce the
      necessity of a careful examination for the whole family with regards to the
      stigmata of Goldenhar syndrome.

PMID- 22611645
TI  - Oesophageal atresia in a neonate with a familial translocation t(1;13)(p8;q12).

PMID- 22611646
TI  - Mosaic trisomy 8 syndrome with a novel finding of ectopic kidney.

PMID- 22611647
TI  - The very rare aglossia adactylia syndrome with a novel finding of mental
      retardation.

PMID- 22611648
TI  - Report from the United States: the U.S. health crisis deepens amid rising
      inequality--a review of data, fall 2011.
AB  - This report presents information on the state of the U.S. health system in late
      2011. The authors include data on the uninsured and the underinsured and their
      access to health care, socioeconomic inequality in care, the rising costs of the
      U.S. health system, and the role of corporate money in health care, with special
      reference to the pharmaceutical industry and the hospice industry. They also
      provide updates on Medicaid and Medicare and on the new federal health care law.
      Some information on health care systems elsewhere in the world is also included.

PMID- 22611649
TI  - Report from China: health insurance in China--evolution, current status, and
      challenges.
AB  - The authors review the evolution of health insurance in China and analyze how it
      has been shaped to its current form by political and economic dynamics. They
      summarize the current status of health insurance in terms of population coverage,
      benefit design, scope of service, and its interaction with providers; address
      challenges regarding future health insurance reform; and propose policy
      recommendations. Although the recent health insurance reform has made major
      breakthroughs in population coverage, it is still too early to judge whether the
      political willingness to appease social unrest can be translated into concrete
      health care protections for the population.

PMID- 22611650
TI  - Report on Honduras: ripples in the pond--the financial crisis and remittances to
      chronically ill patients in Honduras.
AB  - The U.S. financial crisis has affected employment opportunities for Latino
      immigrants, and this could affect their ability to send financial assistance, or
      "remittances", to chronically ill family members in their home country. In a
      cross-sectional survey of 624 chronically ill adults conducted in Honduras
      between June and August 2009, respondents reported their receipt of remittances,
      health service use, and cost-related access barriers. Fifty-four percent of
      respondents reported relatives living outside the country, and of this group, 66
      percent (37% of the overall sample) received remittances. Seventy-four percent of
      respondents receiving remittances reported a decrease over the prior year, mostly
      due to job losses among their relatives abroad. Respondents reporting reductions
      in remittances received significantly less per month, on average, than those
      without a reduction (US $170 vs. $234; p = 0.01). In multivariate models,
      respondents experiencing a reduction in remittances used fewer health services
      and medications due to cost concerns. Remittance payments from relatives resident
      in the United States are a major source of income for chronically ill individuals
      in Latin America. Most recipients of remittances reported a reduction during the
      financial downturn that affected their access to care.

PMID- 22611651
TI  - Competition-based reform of the National Health Service in England: a one-way
      street?
AB  - The Conservative-led government in the United Kingdom is embarking on massive
      changes to the National Health Service in England. These changes will create a
      competitive market in both purchasing and provision. Although the opposition
      Labour Party has stated its intention to repeal the legislation when it regains
      power, this may be difficult because of provisions of competition law derived
      from international treaties. Yet there is an alternative, illustrated by the
      decision of the devolved Scottish government to reject competitive markets in
      health care.

PMID- 22611652
TI  - Ecuador's silent health reform.
AB  - Health sector reform was implemented in many Latin American countries in the
      1980s and 1990s, leading to reduced public expenditure on health, limitations on
      public provision for disease control, and a minimum package of services, with
      concomitant growth of the private sector. At first sight, Ecuador appeared to
      follow a different pattern: no formal reform was implemented, despite many plans
      to reform the Ministry of Health and social health insurance. The authors
      conducted an in-depth review and analysis of published and gray literature on the
      Ecuadorian health sector from 1990 onward. They found that although neoliberal
      reform of the health sector was not openly implemented, many of its typical
      elements are present: severe reduction of public budgets, "universal" health
      insurance with limited coverage for targeted groups, and contracting out to
      private providers. The health sector remains segmented and fragmented, explaining
      the population's poor health status. The leftist Correa government has prepared
      an excellent long-term plan to unite services of the Ministry of Health and
      social security, but implementation is extremely slow. In conclusion, the health
      sector in Ecuador suffered a "silent" neoliberal reform. President Correa's
      progressive government intends to reverse this, increasing public budgets for
      health, but hesitates to introduce needed radical changes.

PMID- 22611653
TI  - Social inequalities in "sickness": does welfare state regime type make a
      difference? A multilevel analysis of men and women in 26 European countries.
AB  - In comparative studies of health inequalities, public health researchers have
      usually studied only disease and illness. Recent studies have also examined the
      sickness dimension of health, that is, the extent to which ill health is
      accompanied by joblessness, and how this association varies by education within
      different welfare contexts. This research has used either a limited number of
      countries or quantitative welfare state measures in studies of many countries. In
      this study, the authors expand on this knowledge by investigating whether a
      regime approach to the welfare state produces consistent results. They analyze
      data from the European Union Statistics on Income and Living Conditions (EU
      SILC); health was measured by limiting longstanding illness (LLSI). Results show
      that for both men and women reporting LLSI in combination with low educational
      level, the probabilities of non-employment were particularly high in the Anglo
      Saxon and Eastern welfare regimes, and lowest in the Scandinavian regime. For
      men, absolute and relative social inequalities in sickness were lowest in the
      Southern regime; for women, inequalities were lowest in the Scandinavian regime.
      The authors conclude that the Scandinavian welfare regime is more able than other
      regimes to protect against non-employment in the face of illness, especially for
      individuals with low educational level.

PMID- 22611654
TI  - Decreasing inequality under Latin America's "social democratic" and "populist"
      governments: is the difference real?
AB  - The article addresses the claim that the "left populist" governments of
      Argentina, Bolivia, Ecuador, and Venezuela failed to effectively reduce
      inequality in the 2000s. The author examines the econometric evidence presented
      by McLeod and Lustig (2011) that the "social democratic" governments of Brazil,
      Chile, and Uruguay were more successful and shows that McLeod and Lustig's
      results are highly sensitive to their use of data from the Socioeconomic Database
      for Latin America and the Caribbean (SEDLAC). Conducting the same analysis using
      inequality data from the Economic Commission for Latin America and the Caribbean
      (ECLAC) suggests the exactly opposite conclusion. The contrast between the
      results obtained using SEDLAC and ECLAC data suggests that the choice of
      inequality data source is not immaterial and that the difference is probably
      driven by how the two sources handle the underreporting of income in household
      surveys. The key difference between SEDLAC and ECLAC data is that the latter
      correct for the underreporting of income while the former do not. Absent
      reasonable criteria for choosing between the two datasets, the author suggests
      that any econometric results pertaining to Latin American income inequality
      should prove robust to both data sources.

PMID- 22611655
TI  - Capital relations and health: mediating and moderating effects of cultural,
      economic, and social capitals on mortality in Alameda County, California.
AB  - Inspired by Bourdieu's theories on various forms of capital, conversions among
      them, and the fields (social spaces) delineated by possession of them, the
      authors investigate distinct and interconnected effects of cultural, economic,
      and social capitals on risk of mortality. Using 35 years of longitudinal data
      from the Alameda County Study (n = 6,157), they created discrete-time hazard
      models to predict all-cause mortality from educational attainment
      (institutionalized cultural capital), household income (economic capital), and
      different forms of personal ties (social capital). The results show that
      education, income, having three or more close friends, regularity of church
      attendance, and participation in social/recreational groups were all negatively
      and significantly associated with risk of mortality. Income mediated a
      significant portion of the education effect. None of the personal ties variables
      mediated the effects of education or income. Relative composition of the sum
      total of education and income did not have an effect. Lastly, examination of
      statistical interactions between capitals determined that protective effects of
      church attendance and participation in community betterment groups applied only
      to non-wealthy people. These findings speak to the structure of the U.S. social
      space within which health-delimiting relationally defined social classes may be
      made manifest.

PMID- 22611656
TI  - Not just smoking and high-tech medicine: socioeconomic inequities in U.S.
      mortality rates, overall and by race/ethnicity, 1960-2006.
AB  - Recent research on the post-1980 widening of U.S. socioeconomic inequalities in
      mortality has emphasized the contribution of smoking and high-tech medicine, with
      some studies treating the growing inequalities as effectively inevitable. No
      studies, however, have analyzed long-term trends in U.S. mortality rates and
      inequities unrelated to smoking or due to lack of basic medical care, even as a
      handful have shown that U.S. socioeconomic inequalities in overall mortality
      shrank between the mid-1960s and 1980. The authors accordingly analyzed U.S.
      mortality data for 1960-2006, stratified by county income quintile and
      race/ethnicity, for mortality unrelated to smoking and preventable by 1960s'
      standards of medical care. Key findings are that relative and absolute
      socioeconomic inequalities in U.S. mortality unrelated to smoking and preventable
      by 1960s' medical care standards shrank between the 1960s and 1980 and then
      increased and stagnated, with absolute rates on a par with several leading causes
      of death, and with the burden greatest for U.S. populations of color. None of
      these findings can be attributed to trends in smoking-related deaths and access
      to high-tech medicine, and they also demonstrate that socioeconomic inequities in
      mortality can shrink and need not inevitably rise.

PMID- 22611657
TI  - "Dualities of interest": the inter-organizational relationships between disease
      specific nonprofits and the pharmaceutical industry.
AB  - Health care and biomedical research environments in the United States are largely
      characterized by strategic relational practices conducted beyond the public gaze.
      The very nature of health care has been widely reconceptualized from a response
      to physical/biological imperatives regulated by health promotion and the
      epidemiological distribution of diseases to profit/market imperatives regulated
      by "product/brand" promotion and market dynamics. At critical decision points
      throughout the system, we find the multinational pharmaceutical industry wielding
      the influence that its wealth and power have bought. This study contributes to
      the growing body of work that seeks to illuminate the relationships between the
      pharmaceutical industry and the various entities that constitute the U.S. health
      and research systems. Through the use of case studies, it examines the
      relationships between the multinational pharmaceutical industry and the large
      disease-specific public and professional nonprofit organizations. It explores
      several questions, including: Is the concept of what constitutes a conflict of
      interest being purposefully manipulated? Is the public benevolence afforded to
      nonprofits extended to their corporate partners in ways that preclude critical
      oversight of relational dynamics? And are public donations, solicited by and
      given in good faith to these organizations, inevitably serving the economic
      interests and profits of donor pharmaceutical companies?

PMID- 22611658
TI  - The World Health Organization and public health research and practice in
      tuberculosis in India.
AB  - Two major research studies carried out in India fundamentally affected
      tuberculosis treatment practices worldwide. One study demonstrated that home
      treatment of the disease is as efficacious as sanatorium treatment. The other
      showed that BCG vaccination is of little protective value from a public health
      viewpoint. India had brought together an interdisciplinary team at the National
      Tuberculosis Institute (NTI) with a mandate to formulate a nationally applicable,
      socially acceptable, and epidemiologically sound National Tuberculosis Programme
      (NTP). Work at the NTI laid the foundation for developing an operational research
      approach to dealing with tuberculosis as a public health problem. The starting
      point for this was not operational research as enunciated by experts in this
      field; rather, the NTI achieved operational research by starting from the people.
      This approach was enthusiastically welcomed by the World Health Organization's
      Expert Committee on Tuberculosis of 1964. The NTP was designed to "sink or sail
      with the general health services of the country." The program was dealt a major
      blow when, starting in 1967, a virtual hysteria was worked up to mobilize most of
      the health services for imposing birth control on the people. Another blow to the
      general health services occurred when the WHO joined the rich countries in
      instituting a number of vertical programs called "Global Initiatives". An ill
      conceived, ill-designed, and ill-managed Global Programme for Tuberculosis was
      one outcome. The WHO has shown rank public health incompetence in taking a very
      casual approach to operational research and has been downright quixotic in its
      thinking on controlling tuberculosis worldwide.

PMID- 22611659
TI  - Plunging into the pool of death: imagining a dangerous outcome influences
      distance perception.
AB  - We examined whether manipulating the imagined consequences of falling would
      influence the perception of height, distance, and size. In experiment 1, height
      and size perception were measured when participants stood at a short height (0.89
      m) or a medium height (1.91 m) above either an empty pool or a pool filled with a
      bed of nails. Participants who viewed the bed of nails and imagined falling into
      it estimated both the height as taller and the size of the bed of nails as larger
      than participants who imagined falling into an empty pool. In a second
      experiment, participants overestimated the horizontal ground distance to and
      across the bed of nails after being told to imagine jumping over it. Overall,
      these experiments suggest that costs associated with imagined actions can
      influence the perception of both vertical and horizontal extents that are not
      inherently dangerous.

PMID- 22611660
TI  - Contrast polarity preservation's role in perception: explained and unexplained
      stimuli.
AB  - Roncato and Casco (2003, Perception & psychophysics 65 1252-1272) had shown that
      in situations where the Gestalt principle of good continuity is put into conflict
      with preservation of contrast polarity (CP) the perception that preserves CP
      prevails. Parlangeli and Roncato (2010, Perception 39 255-259) have studied this
      question of preservation of CP more closely and have added an addendum to the
      rule. They have used stimuli consisting of a checkerboard of perpendicularly
      arranged rectangular bricks (white, gray, or black) and draughtsmen white, gray,
      or black disks placed at the corners of the bricks. This study has caused them to
      add an addendum to the rule of CP-preserved path-conjunction binding: if there
      are two contour completions that preserve the CP, the one with the higher
      contrast will prevail. Parlangeli and Roncato find that, for certain shades of
      the disks and bricks, the perpendicular lines of the checkerboard appear
      strikingly to be slanted or undulating. Here we consider all possible
      arrangements of relative magnitudes of checkerboards consisting of bricks of two
      different shades and disks of two shades as well, as such arrangements with
      widely varying differences in the magnitude of brightness. We have found a number
      of cases where the perception is not explained by the rule and addendum of
      Roncato and Casco, and Parlangeli and Roncato, and a case where preservation of
      "distant" as well as local CP plays a role in perception. The previously known
      cases, and the new exceptional unexplained stimuli we have found, warrant further
      study.

PMID- 22611661
TI  - Spatial judgments in the horizontal and vertical planes from different vantage
      points.
AB  - Todorovic (2008 Perception 37 106-125) reported that there are systematic errors
      in the perception of 3-D space when viewing 2-D linear perspective drawings
      depending on the observer's vantage point. Because these findings were restricted
      to the horizontal plane, the current study was designed to determine the nature
      of these errors in the vertical plane. Participants viewed an image containing
      multiple colonnades aligned on parallel converging lines receding to a vanishing
      point. They were asked to judge where, in the physical room, the next column
      should be placed. The results support Todorovic in that systematic deviations in
      the spatial judgments depended on vantage point for both the horizontal and
      vertical planes. However, there are also marked differences between the two
      planes. While judgments in both planes failed to compensate adequately for the
      vantage-point shift, the vertical plane induced greater distortions of the
      stimulus image itself within each vantage point.

PMID- 22611662
TI  - Sequential effects in face-attractiveness judgment.
AB  - A number of studies have shown that current-trial responses are biased toward the
      response of the preceding trial in perceptual decisionmaking tasks (the
      sequential effect-Holland and Lockhead, 1968 Perception & Psychophysics 3 409
      414). The sequential effect has been widely observed in evaluation of the
      physical properties of stimuli as well as more complex properties. However, it is
      unclear whether subjective decisions (e.g., attractiveness judgments) are also
      susceptible to the sequential effect. Here, we examined whether the sequential
      effect would occur in face-attractiveness judgments. Forty-eight pictures of male
      and female faces were presented successively. Participants rated the
      attractiveness of each face on a 7-point scale. The results showed that the
      attractiveness rating of a given face assimilated toward the rating of the
      preceding trial. In a separate experiment, we provided the average attractiveness
      rating by others for each trial as feedback. The feedback weakened the sequential
      effect. These findings suggest that attractiveness judgment is also biased toward
      the preceding judgment, and hence the sequential effect can be extended into the
      domain of subjective decisionmaking.

PMID- 22611663
TI  - Perceptual filling-in of negative coloured afterimages.
AB  - Filling-in of brightness, colour, and texture refers to the perceptual spreading
      of surround features onto the target area. This phenomenon has been extensively
      investigated in real images. Here, we study colour spreading in afterimages of
      disk-ring patterns, using a variety of colour combinations. We show that colour
      filling-in and filling-out in afterimages follow rules different from those found
      for real images, suggesting that the brain treats afterimages as genuine
      'stimuli'.

PMID- 22611664
TI  - The 'double face' illusion.
AB  - We report three experiments intended to characterise aspects of the 'double face'
      illusion, formed by replicating the eyes and mouth below the originals. Such
      doubled faces are disturbing to look at. We find there are wide individual
      differences in the ability to detect that a face has been doubled when presented
      briefly and masked. These differences appear to relate to perceptual speed, since
      they correlate with the ability to identify a briefly presented famous face.
      Doubling has a significant effect on identification, though much less than
      inversion. In a reaction-time study, participants are faster to decide that a
      face has been doubled as it is rotated away from upright. The final study shows
      that normal and doubled faces do not pop out from each other, but reveals a
      processing overhead of 40-60 ms per doubled face. We offer some speculations as
      to the cause of the perceptual effects.

PMID- 22611665
TI  - Mapping the tip of the tongue--deprivation, sensory sensitisation, and oral
      haptics.
AB  - We investigated the impact of food deprivation on oral and manual haptic size
      perception of food and non-food objects. From relevant theories (need
      proportional perception, motivated perception, frustrative nonreward, perceptual
      defence, and sensory sensitisation) at least four completely different competing
      predictions can be derived. Testing these predictions, we found across four
      experiments that participants estimated the length of both non-food and food
      objects to be larger when hungry than when satiated, which was true only for oral
      haptic perception, while manual haptic perception was not influenced by hunger
      state. Subjectively reported hunger correlated positively with estimated object
      size in oral, but not in manual, haptic perception. The impact of food
      deprivation on oral perception vanished after oral stimulations even for hungry
      individuals. These results favour a sensory sensitisation account maintaining
      that hunger itself does not alter oral perception but the accompanying lack of
      sensory stimulation of the oral mucosa. Both oral and manual haptic perception
      tended to underestimate actual object size. Finally, an enhancing effect of
      domain-target matching was found, ie food objects were perceived larger by oral
      than by manual haptics, while non-food objects were perceived larger by manual
      than by oral haptics.

PMID- 22611666
TI  - Geometric specification of dynamics: learning to visually perceive kinetic
      quantities from static images.
AB  - In a single experiment, perceivers viewed computer-generated hammer-like objects
      and estimated a kinetic property. Each hammer comprised a cylinder of some
      diameter and height, attached to a handle-a second cylinder of fixed diameter and
      variable length. On 5 blocks of trials, three groups of perceivers reported a
      property reflecting mass, torque, or moment of inertia. Blocks 2-4 were training
      blocks on which numerical feedback was given. On blocks 6 and 7, perceivers were
      asked to report the kinetic properties not reported on blocks 1-5. We were
      interested in how geometrical object properties affected the perception of
      kinetic properties, and how that perception changed with experience. To determine
      how geometrical object properties informed reports of kinetics, a continuous
      information space of head diameter and height, and handle length was created, and
      perceivers' loci within that space were determined. Perceivers began at various
      distances from the optimum for the to-be-reported property and were closer to the
      optimum after training. On blocks 6 and 7, performance did not reflect transfer
      from training on another property. The results were interpreted in the context of
      the theory of direct learning.

PMID- 22611667
TI  - New twists for an old turning illusion.
AB  - A Vernier-offset illusion induced by rotating lines, introduced by Matin et al
      (1976 Perception & psychophysics 20 138-142) was re-examined using onset, offset,
      and reverse trajectories inspired by flash-lag illusion research, with both
      Vernier and alignment-with-vertical judgments being recorded. The pattern of
      illusions found was generally in agreement with a differential latency of
      stimulus ends account described by those authors, although certain variants of
      modern spatial projection theories, and a differential latency of attribute
      account, could also accommodate much of the data.

PMID- 22611668
TI  - Still motion? Motion illusions and luminance contrast.
AB  - The influence of different luminance contrasts and equiluminance on illusory
      motion in four inducing patterns was studied: enigma, rotating snakes, pinna, and
      rotating-tilted-lines. At high luminance contrast the Pinna and the rotating
      tilted-lines illusions are significantly stronger than at low luminance contrast,
      whereas the Enigma and Rotating Snakes illusions are stronger at low luminance
      contrast. At equiluminance along the L-M axis the strength of all illusions is
      greatly reduced. Data suggest that luminance contrast constitutes one important
      factor for their occurrence.

PMID- 22611669
TI  - A new "fat face" illusion.
AB  - We report a novel fat face illusion that when two identical images of the same
      face are aligned vertically, the face at the bottom appears 'fatter'. This
      illusion emerged when the faces were shown upright, but not inverted, with the
      size of the illusion being 4%. When the faces were presented upside down, the
      illusion did not emerge. Also, when upright clocks were shown in the same
      vertically aligned fashion, we did not observe the illusion, indicating that the
      fat illusion does not generalize to every category of canonically upright objects
      with similar geometric shape as a face.

PMID- 22611670
TI  - Judging body weight from faces: the height-weight illusion.
AB  - Being able to exploit features of the human face to predict health and fitness
      can serve as an evolutionary advantage. Surface features such as facial symmetry,
      averageness, and skin colour are known to influence attractiveness. We sought to
      determine whether observers are able to extract more complex features, namely
      body weight. If possible, it could be used as a predictor for health and fitness.
      For instance, facial adiposity could be taken to indicate a cardiovascular
      challenge or proneness to infections. Observers seem to be able to glean body
      weight information from frontal views of a face. Is weight estimation robust
      across different viewing angles? We showed that participants strongly
      overestimated body weight for faces photographed from a lower vantage point while
      underestimating it for faces photographed from a higher vantage point. The
      perspective distortions of simple facial measures (e.g., width-to-height ratio)
      that accompany changes in vantage point do not suffice to predict body weight.
      Instead, more complex patterns must be involved in the height-weight illusion.

PMID- 22611671
TI  - [Prediction of outcomes of moderate and severe brain injury and cerebral trauma
      in victims evacuated from the warfare].
AB  - The aim was to estimate predictors and prognostic models of the nearest outcomes
      in moderate and severe traumatic brain injury. Authors have analyzed 75 medical
      histories of patients with moderate and severe traumatic brain injury. Methods of
      multiple linear regression and treelike classification were used for the
      construction of prognostic models. The most significant predictors as a part of
      prognostic models of the present study were: scores of the Glasgow coma scale and
      its elements, condition of corneal reflex, expression of pyramidal insufficiency,
      level of leukocytosis, levels of blood urea, urination disturbance, average heart
      rate. The results obtained confirm the prognostic value of the Glasgow coma
      scale. The additional account of the indicators characterizing the expression of
      inflammatory processes and organ insufficiency allows to significantly improve
      the prognostic models of outcomes in patients with traumatic brain injury.

PMID- 22611672
TI  - [Psychological aspects of systemic approach to diagnostics of mental and
      immunological disorders in diffuse-nodular form of Hashimoto's thyroiditis].
AB  - Authors have studied 162 patients with the diffuse-nodular form of chronic
      autoimmune thyroiditis (AIT). Alexithymic personality type was found to be
      prevalent in patients in the euthyroid phase (51.9%). In autoimmune thyroiditis,
      alexithymia and certain cytokine parameters were correlated with
      psychopathological symptoms as asthenia, anxiety and depression which might be
      caused by their participation in the pathogenesis of non-psychotic mental
      disorders during the euthyroid phase. The linkage of alexithymia with certain
      emotional-personal parameters allows to regard it as one of the components of the
      integral personality characteristics. These findings show that alexithymia is not
      only an indirect risk factor of the autoimmune thyroiditis development but also a
      predictor of the disease course.

PMID- 22611673
TI  - [Idiopathic focal epilepsies of infancy and childhood].
AB  - We studied 1036 children with epileptic seizures, aged from 1 to 18 years, during
      2004-2008. One hundred and six patients were diagnosed with idiopathic focal
      epilepsy (IFE). The following forms of IFE were singled out: benign seizures of
      infancy (familial and non-familial) - Watanabe--Vigevano syndrome - 5,7%,
      occipital epilepsy of childhood with early manifestation (Panayiotopoulos
      syndrome) -26,4%, occipital epilepsy of childhood with late manifestation
      (Gastaut syndrome) - 12,3%, benign epilepsy of childhood with central-temporal
      spikes (rolandic epilepsy) - 51%, benign focal epilepsy with affective symptoms -
      4,7%. The efficacy of the first monotherapy was significantly worse in rolandic
      epilepsy compared to the other IFE forms. Prescription of valproate or the
      combination of valproate, ethosuximidum and levetiracetam, in case of resistant
      course, as a starting therapy was found optimal.

PMID- 22611674
TI  - [Clinical experience in using agomelatin (valdoxan) in the neurological
      practice].
AB  - The author presents the own clinical experience of the use of agomelatin
      (valdoxan) in the complex treatment of patients with ischemic stroke, migraine,
      fibromyalgia and during "drug holidays" after the withdrawal of benzodiazepines.
      In all cases of comorbid neurological diseases and clinically diagnosed insomnia
      and depression, valdoxan demonstrated its efficacy and safety.

PMID- 22611675
TI  - [Mexiprim in the complex treatment of patients with cervical dorsopathy and the
      vertebral artery syndrome].
AB  - Fifty patients with cervical dorsopathy with the vertebral artery syndrome were
      studied using clinical scales (neurological deficit, psychoemotional
      disturbances) and laboratory methods (parameters of oxidant stress). The
      correlations between the oxidant stress and the dynamics of neurological
      syndromes and psychoemotional disturbances as well as the efficacy and safety of
      their treatment with antioxidants (mexiprim) were determined.

PMID- 22611676
TI  - [The assessment of the clinical efficacy, vasoactive and metabolic effects of
      mexidol in elderly patients with discirculatory encephalopathy].
AB  - Forty patients, aged from 55 to 74 years, with chronic cerebral ischemia -
      discirculatory encephalopathy, stages I--II, against the background of arterial
      hypertension and atherosclerosis were studied. Patients were randomized into 2
      equal groups. Patients of the main group received the antioxidant mexidol
      intramuscular in dose 100 mg during the first 10 days and then perorally in dose
      125 mg three times a day during 20 days in the combination with the regular
      treatment (diroton in dose 5-20 mg daily, cardiomagnyl in dose 75 mg daily).
      Patients of the control group received regular treatment during 30 days. The
      efficacy was evaluated at baseline, on the 10th and 30th days after the treatment
      using clinical scales (the number of complaints, neurological deficit, cognitive
      and emotional disorders), parameters of cerebral hemodynamics measured with
      transcranial duplex scanning, laboratory indices of the state of oxidant and
      antioxidant systems (the content of malonic dialdehyde and superoxide dismutase
      in the blood plasma as well as the plasma total antioxidant activity). The
      statistically significant (p<0.05-0.01) reduction in the severity of asthenic and
      anxiety disorders, the improvement of static-locomotor and cognitive functions as
      well as of parameters of cerebral hemodynamics due to the decrease in the
      peripheral vascular resistance and the normalization of venous outflow from the
      cavity of scull was seen in patients treated with mexidol compared to the
      baseline and the control group. Mexidol significantly reduced the intensity of
      lipid peroxidation and increase the total antioxidant activity of the blood. The
      results obtained in the study allow to consider mexidol as the effective drug in
      the complex treatment of discirculatory encephalopathy in elderly patients.

PMID- 22611677
TI  - [Differential diagnosis of spasm and hypoplasia of the vertebral artery with
      ultrasound methods].
AB  - The aim of the study was to establish ultrasound criteria of the differentiation
      between functional and morphological vasoconstriction of the vertebral artery
      (VA) using hypercapnia test in patients with signs of vertebral-basilar
      insufficiency. The inclusion criteria were the presence of clinical symptoms of
      vertebral-basilar disturbances of circulation and small diameter of VA (< or =2.9
      mm). Fifty patients, aged from 17 to 57 years, were studied. Based on the form of
      Doppler 's spectrum of the blood flow in the small VA, patients were stratified
      into three groups: normal (N spectrum), peak-like split (PS spectrum) and high
      resistance low-speed (HL spectrum). The increment of diameter by 0.2 mm and more,
      i.e. the functional vasoconstriction (spasm) during hypercapnia, was
      characteristic of patients with PS and N spectrum. The ROC-analysis revealed that
      the absence of VA increment during hypercapnia is a highly specific (90.9%)
      predictor of morphological vasoconstriction of VA. Quantitative criteria of VA
      hypoplasia were specified as well. Ultrasound angioscanning in the combination
      with hypercapnia test allows differentiation with a high probability between
      functional (spasm) and morphological (hypoplasia) vasoconstriction of VA.

PMID- 22611678
TI  - [Prognostic value of hemorheologic and morphodensitometric parameters of blood
      cells for the progression of cerebrovascular insufficiency].
AB  - Authors have studied 484 patients, aged from 35 to 55 years (mean - 41.0+/-1.4
      years), in the early stages of cerebrovascular insufficiency. Computed
      morphodensitometry of erythrocytes, the study of their deformation and
      aggregation capacity have been used. It have studied the subpopulation content of
      erythrocytes and determined their morphometric parameters. The
      morphodensitometric changes in erythrocytes were correlated with disturbances of
      their functions (aggregation properties, deformation, gas transfer ability) that
      had the most impact on the hemodynamics of the microcirculation stream. Clinical
      and laboratory studies revealed that the morphofunctional changes in erythrocytes
      appeared earlier and played a key pathogenetic role in the formation and
      progression of cerebral ischemic hypoxia.

PMID- 22611679
TI  - [Adhesion molecule in the cerebrospinal fluid in multiple sclerosis].
AB  - Levels of adhesion molecules were measured in 24 patients with multiple sclerosis
      during the 3-years prospective study. The high level of adhesion molecules sPECAM
      in the cerebrospinal fluid was associated with the appearance of new foci
      according to the magnetic resonance imaging data as well as with quick
      disability.

PMID- 22611680
TI  - [Problems of the advancement of psychiatric care and the development of public
      health care].

PMID- 22611681
TI  - [The origins of the formation of the Kraepelin's concept of dementia praecox and
      Bleuler's concept of schizophrenia].

PMID- 22611682
TI  - [Potentials of the neuroprotective treatment of polymodal action in acute and
      early rehabilitation period of stroke].

PMID- 22611683
TI  - [Cognitive disturbances in children with anxiety-phobic disorders].

PMID- 22611684
TI  - [Cytokines in male patients with the serious brain injury].

PMID- 22611685
TI  - [Some clinical features of the malignant neuroleptic syndrome].

PMID- 22611686
TI  - [International experience in studying effects of omega-3 polyunsaturated fatty
      acids: the influence on cognitive abilities and some mental disorders].

PMID- 22611687
TI  - [The antithrombotic treatment in the secondary prevention of ischemic stroke:
      strategy and tactic issues].

PMID- 22611688
TI  - [Psychogenic trauma, its consequences and predisposing factors].

PMID- 22611689
TI  - [Physiologic foundations and some perspectives of the further development of
      antiepileptic drugs].

PMID- 22611690
TI  - [Epidemiology, medical and social features of the addiction to beer and strong
      alcogol].
AB  - The comparative study of the addiction to beer and hard liquor was carried out.
      Despite of the dramatic increase in the beer consumption in the Russian
      Federation between 1999 and 2009, the incidence and prevalence of alcohol
      dependence and alcohol psychoses had decreased. The analysis of preference in
      alcohol consumption revealed that 90.7% of study participants consumed different
      types of alcohol beverages: beer and hard liquor. Alcohol addiction caused by the
      consumption of beer or spirits and wine alone was 1.2% and 8.1%, respectively.
      Our study of case histories demonstrated that alcohol addiction related
      predominantly to the beer use was associated with the consumption of smaller
      doses of pure ethanol, less pronounced abstinent syndrome, less frequent
      complications, such as the convulsive syndrome and alcoholic psychosis, compared
      to the addiction to hard liquor. The examination of 106 outpatients with alcohol
      addiction revealed that patients who preferred hard liquor during the last month
      consumed more alcohol in terms of pure ethanol. Also, the period of hard drinking
      was longer and patients had more social, legal, and psychological problems as
      well as somatic and psychopathological disorders. The higher was the consumption
      of hard liquor, the severe was the course of alcohol addiction. The least number
      of biopsychosocial problems was noted in patients who consumed only beer.

PMID- 22611691
TI  - [Clinical and psychological characteristics of patients with personality
      disorders complicated by alcohol dependence].
AB  - The goal of the current study was to compare the course of relapse of alcohol
      dependence in patients with and without personality disorders. We studied 68
      patients with alcohol dependence in the stage of decompensation and comorbid
      personality disorder, and 43 patients with lucid alcohol dependence. The patients
      were studied using a clinical examination and a battery of psychological tests.
      The group of patients with alcohol dependence and personality disorder was found
      to have better prognosis than the group with lucid alcoholism, with the exception
      of patients with histrionic personality disorder who had the lower self-esteem,
      primitive psychological defense mechanisms, lack of insight, poor social
      functioning, low stress tolerance, and a dysphoric variant of affective
      disorders.

PMID- 22611692
TI  - [Current peculiarities of alcoholic psychosis].
AB  - The follow-up study of alcoholic psychoses in male patients admitted to a
      clinical department of a psychiatric hospital in 2005-2007 was carried out.
      Patients with alcoholic psychoses made up from 15 to 30% of all patients. The
      number of psychosis had seasonal variations with the elevations in spring and
      autumn, peaks in January, lune and October. Alcoholic delirium morbidity made up
      from 69 to 82% of the total number of alcoholic psychoses, alcoholic hallucinosis
      varied from 14 to 27%. Other forms were presented by single cases. In alcoholic
      delirium hallucinations had brighter, sated character. The most specific were
      visual hallucinations in the form of zoohallucinations, hallucinations of an oral
      cavity ("sensation of threads, hair etc"). The most often observable characters
      were "extraneous people, animal, demons". In alcoholic hallucinosis, verbal
      contrast hallucinations, making comment hallucinations, visual illusions were
      most frequent. The family history of mental disorders and alcoholism was noted in
      30% of patients with alcoholic psychosis. The probability of occurrence of
      alcoholic psychoses depended on the quality of consumed drinks. The presence of a
      cranial-brain injury in the anamnesis considerably aggravated the disease
      forecast and increased the risk of seizure syndrome.

PMID- 22611693
TI  - [Mental disorders following delirium tremens].
AB  - Twenty-four patients, aged between 29-62 years (average age - 44+/-11 years), at
      the post-psychosis period of delirium tremens were observed. In 19 patients, this
      period was characterized by a triad of mental disorders including cognitive
      dysfunction, affective disturbances and alcohol anosognosia. Memantine was
      recommended for all patients with mental disorders. These disorders are reduced
      during 11-28 (in average - 18+/-4) days after the recovery of psychosis. The
      hypothesis on the close relationship of three types of described disorsers with
      mild forms of Korsakoff disease and the expediency of memantine therapy after the
      delirium tremens was expressed.

PMID- 22611694
TI  - [The questionnaire "alcohol anosognosia" is a new tool for assessment of
      anosognosia in patients with alcohol dependence].
AB  - The aim of this study was to develop and validate a patient-rated questionnaire
      for the complex express-assessment of alcohol anosognosia. The questionnaire was
      tested in 106 inpatients diagnosed with alcohol dependence (ICD-10, item F10.2).
      The age of the study participants (M+/-SD) was 42.1+/-8.8 years, duration of
      alcohol dependence 11.3+/-7.0 years. The questionnaire consisted of 7 subscales:
      Not being in the know, Non-recognition of disease symptoms, Non-recognition of
      disease in whole, Non-recognition of disease consequences, Emotional rejection of
      disease, Disagreement with treatment, Non-acceptance of temperance. Psychometric
      characteristics (external-criterion validity, test-retest validity, internal
      consistency) were studied and the standardization of the questionnaire was
      performed. Mean empiric values of subscales were determined. The questionnaire
      allows to get the complex assessment of anosognosia level by separate components
      and to present the profile of alcohol anosognosia as well.

PMID- 22611695
TI  - [Psychotherapy of alcoholics based on personality traits].
AB  - The article describes results of the development of the differentiated
      application of psychotherapeutic methods to the treatment of 120 patients with
      alcoholism basing on their personality characteristics. Psychotherapeutic
      programs oriented towards the characterologic features of patients are presented.
      These programs allowed to single out 4 groups of patients. The differentiated
      application of psychotherapy in these groups increased the effectiveness of
      treatment. As a result, the remission was achieved in 94 patients.

PMID- 22611696
TI  - [The risk of sudden cardiac death in patients with alcohol addiction: how urgent
      is a problem?].
AB  - Features and variants of cardiovascular pathology among patients with alcohol
      addiction were analyzed in 251 patients with II-III degrees of alcohol addiction
      during 3 years. Treatment and compliancy of patients were taken into account.
      Based on the results of the primary clinical and instrumental examination,
      patients were divided into two groups depending on the presence (181 patients) or
      the absence (70 patients) of cardiovascular pathology. Mortality rates, including
      sudden death, and cardiac complications were significantly higher in patients
      with cardiovascular pathology. The impact of patient's compliance on these
      indices has been revealed.

PMID- 22611697
TI  - [Alcohol-induced liver injury].

PMID- 22611698
TI  - [Peculiarities of erectile dysfunction in men with alcohol dependence].
AB  - To verify the etiopathogenic structure of erectile dysfunction in alcohol
      dependence, we have investigated 80 men with erectile dysfunction and alcohol
      dependence (the main group) and 40 men with erectile dysfunction without alcohol
      dependence (the control group). Endocrine and vasculogenic forms of erectile
      dysfunction were more frequent in men with alcohol dependence as compared to men
      without alcohol dependence, and the presentation of sexual disorder was
      complicated due to the increase in the number of accompanying syndromes. At the
      same time, as alcohol dependence progresses, the part of organic forms of
      erectile dysfunction and the number of syndromes which accompany erectile
      dysfunction increase.

PMID- 22611699
TI  - [Suicidal and personality characteristics of women married to men with alcohol
      dependence and suicidal activity].
AB  - The effect of the suicidal activity in men with alcohol dependence on suicidal
      indexes, personal-codependency and psychological specifics of their wives has
      been studied. It has been found that women married to suicidal men with alcohol
      dependence significantly more frequently demonstrate suicidal activity (a
      phenomenon of suicidal matrimonial comorbidity) compared to wives of "non
      suicidal" men. They also reveal non-suicidal behavioral patterns more frequently
      and prosuicidal predictors are quite common in them. This contingent of women has
      high suicidal potential that needs special attention during the therapeutic work.

PMID- 22611700
TI  - [The comparative analysis of patients with co-morbid psychiatric and substance
      abuse pathologies in follow-up outpatients].
AB  - The findings of the comparative analysis of patients with alcohol dependence and
      psychopathology are presented. The main group (active follow-up) comprised 33
      patients who had committed socially dangerous actions and the control follow-up
      group comprised 75 patients. Between-group differences in personality changes,
      specifics of the alcohol-use component of the comorbid disorder and
      responsiveness to psychotherapy are shown.

PMID- 22611701
TI  - [The use of different forms of naltrexone in the treatment of opioid dependence].
AB  - The authors compared the results of own studies and foreign publications on the
      use of different formulations of naltrexone (peroral, implantable, injectable)
      for the remission stabilization and relapse prevention in patients with opioid
      dependence. Opioid antagonists, in particular naltrexone, are the unique
      medication for the specific pharmacotherapy of opioid dependence currently
      approved in the Russian Federation. The main problem that considerably reduces
      the efficacy and restricts the use of naltrexone in the treatment of opioid
      dependence is the problem of compliance. Nevertheless, in the double blind
      randomized placebo-controlled trials, we have demonstrated the higher efficacy of
      peroral naltrexone for the remission stabilization compared to analogous foreign
      publications. It might be explained by the cultural specifics of the family in
      the Russia Federation, in particular, by the possibility to control the treatment
      by relatives of the patient. However the possibilities of this control are
      significantly reduced as the patient gets older. Long-acting depot formulations
      of naltrexone (implantable and injectable) are more effective than peroral ones
      that allows to solve the problem of compliance and opens new perspectives in the
      treatment of opiate dependence.

PMID- 22611702
TI  - [Methodological principles of the psychological study of patients with alcohol
      dependence].

PMID- 22611703
TI  - Good things come in small packages.

PMID- 22611704
TI  - 2011 JCO orthodontic practice study. Part 4 additional breakdowns.

PMID- 22611705
TI  - The G-chain and miniscrew anchorage: simple mechanics for molar uprighting.

PMID- 22611706
TI  - A modified plier for crimping a double-back bend.

PMID- 22611707
TI  - A space maintainer for growing patients with avulsed central incisors.

PMID- 22611708
TI  - Simple reactivation of a Haas expansion screw.

PMID- 22611709
TI  - The readers' corner. Dental trauma. Hobbies.

PMID- 22611710
TI  - Micro-implant positioning guide.

PMID- 22611711
TI  - Color-coded elastomeric modules for elastics placement.

PMID- 22611712
TI  - Palatal clips for canine retraction.

PMID- 22611713
TI  - Securing a lingual retainer wire with orthodontic separators.

PMID- 22611714
TI  - Distalization of an ectopic molar in the early mixed dentition.

PMID- 22611715
TI  - Eruption control of maxillary second molars with a segmental overlay wire.

PMID- 22611716
TI  - Maxillary molar intrusion with a single miniscrew and a transpalatal arch.

PMID- 22611717
TI  - Ultrasound-assisted catheter-directed thrombolytic therapy for management of
      acute pulmonary embolism.
AB  - Acute pulmonary embolism (PE) is a common and potentially lethal condition.
      Anticoagulation is considered the mainstay therapy while systemic thrombolytic
      therapy is reserved only for patients who are hemodynamically unstable. However,
      therapy for PE with evidence of right ventricular strain is not well-defined. We
      report a case of PE treated successfully with an ultrasound-assisted catheter
      directed thrombolytic therapy.

PMID- 22611718
TI  - Pancreaticopleural fistula: an unusual cause of pleural effusion.
AB  - Pleural effusions are commonly seen in pancreatitis. They usually arise from the
      transdiaphragmatic transfer of exudative fluid during an episode of acute
      pancreatitis and resolve spontaneously. Rarely, in patients with chronic
      pancreatitis, pleural effusions can result from the development of a fistulous
      connection between the pancreas and pleural space; that is, a pancreaticopleural
      fistula. The authors present a case of a patient with a pancreaticopleural
      fistula and then review this rare but important entity.

PMID- 22611719
TI  - Major adverse cardiac events among postpercutaneous coronary intervention
      patients on clopidogrel and proton pump inhibitors.
AB  - OBJECTIVE: To determine if concomitant use of proton pump inhibitors (PPIs) and
      clopidogrel is associated with adverse events among postpercutaneous coronary
      intervention (PCI) patients. METHODS: This is a single-center, retrospective case
      control study of 3,287 consecutive patients on clopidogrel who underwent PCI.
      Univariate and multivariate analyses determined if concomitant PPI and
      clopidogrel use was associated with major adverse cardiac events (MACE). RESULTS:
      There were significantly more deaths (3.0% vs 1.1%; P < 0.001), repeat
      revascularizations (3.8% vs 2.1%; P = 0.005) and MACE (7.1% vs 3.5%; P < 0.001)
      in the clopidogrel and PPI group. Cox regression revealed that PPI is an
      independent predictor of MACE (HR 1.70, 95% CI of 1.20-2.41; P = 0.003),
      mortality (HR 1.79; 95% CI 1.03-3.12, P = 0.038), and target-vessel
      revascularization (HR 1.75; 95% CI 1.12-2.72, P = 0.014). CONCLUSIONS:
      Concomitant use of PPIs and clopidogrel among post PCI patients was associated
      with increased rates of all-cause mortality, target vessel revascularization, and
      combined MACE at nine months follow-up.

PMID- 22611720
TI  - Effect of early enteral tube feeding on patient outcome following
      pancreaticoduodenectomy.
AB  - OBJECTIVE: Morbidity after pancreaticoduodenectomy (PD) is nearly 50%. In this
      study we analyzed if early enteral nutrition via feeding tube (FT) contributes to
      better patient outcomes. MATERIALS AND METHODS: Patients undergoing PD from 2003
      2010. FTs were placed routinely before August 2006, and omitted thereafter. Short
      term outcome measures included: time to start of oral diet, need for total
      parenteral nutrition (TPN), morbidity and mortality, pancreatic fistula,
      complications from FT, hospital length of stay, and disposition. Long-term
      outcome measures included time to start adjuvant therapy, and survival. RESULTS:
      N = 59 (25 had FT, 34 did not). Adenocarcinoma was found in 88%. Early
      institution of tube feeding had no positive impact on any of the outcome
      measures. There were three FT-related complications. CONCLUSIONS: Our results
      demonstrate that FT placement does not improve short-term or long-term outcomes
      after PD. Moreover, major complications can result from FT placement. We do not
      advocate the routine use of FT after PD.

PMID- 22611721
TI  - Starting your own recertification business.

PMID- 22611722
TI  - Evaluation of leadership skills during the simulation education course for the
      initial management of blunt trauma.
AB  - Leadership skills of senior residents, trauma fellows, and a nurse practitioner
      were assessed during simulation training for the initial management of blunt
      trauma. This was a pilot, observational study, that in addition to skill
      development and assessment also sought to determine the need for a dedicated
      leadership training course for surgical residents. The study evaluated the
      leadership skills and adherence to Advance Trauma Life Support (ATLS) guidelines
      of the team leaders during simulation training. The team leaders' performances on
      criteria regarding prearrival planning, critical actions based on ATLS, injury
      identification, patient management, and communication were evaluated for each of
      five blunt-trauma scenarios. Although there was a statistically significant
      increase in leadership skills for performing ATLS critical actions, P < 0.05,
      there were 10 adverse events. A structured simulation program dedicated to
      developing skills for team leadership willbe a worthwhile endeavor at our
      institution.

PMID- 22611723
TI  - The ObGyn clerkship: are students denied the opportunity to provide patient care
      and what is the role of gender?
AB  - OBJECTIVE: We sought to study the frequency, and reasons that third-year medical
      students on an ObGyn clerkship are denied the opportunity to be involved in
      patient care. METHODS: Students from four hospitals affiliated with the
      University of Connecticut Medical School completed an anonymous postclerkship
      survey. RESULTS: Among the 157 students studied (66 males and 91 females), 51% (n
      = 80) were denied the opportunity to participate in a gynecologic examination and
      47% (n = 73) were denied the opportunity for routine ObGyn care by patients.
      Among these students, 55% (n = 44) and 38% (n = 28) stated that being male was
      the reason they were excluded from gynecologic and routine care, respectively. Of
      the 80 students who were denied involvement in a gynecologic examination, 81% (n
      = 65) were denied involvement by clinic patients. Of the 44 males who stated they
      were denied the opportunity to be involved in a gynecologic examination due to
      their gender, 89% (n = 39) were refused by clinic patients. Compared with female
      students, male students are statistically more likely to be denied the
      opportunity to be involved in gynecologic examinations (RR = 1.69 [1.24-2.29]),
      especially by clinic patients (RR = 2.07 [1.41-3.03]). CONCLUSION: A significant
      number of students were denied the opportunity to be involved in ObGyn care
      experiences. More frequently male students were denied involvement in care, with
      a higher incidence among clinic patients. We hypothesize that being denied
      involvement provides a negative perception of the ObGyn specialty, especially to
      male students, possibly affecting their decision to choose ObGyn training.
      PRECIS: A significant number of medical students, particularly males, were denied
      involvement in patient care, primarily by clinic patients, during the ObGyn
      clerkships.

PMID- 22611724
TI  - The president's page. 1962.

PMID- 22611725
TI  - CEPAC and comparative effectiveness research.

PMID- 22611726
TI  - Connecticut Medicine roundtable: Comparative Effectiveness Public Advisory
      Council (CEPAC).

PMID- 22611728
TI  - Attitude and gratitude.

PMID- 22611727
TI  - Top docs.

PMID- 22611729
TI  - Advocacy starts at home, not under the golden dome.

PMID- 22611730
TI  - "Doctors still face harsh medical liability realities".

PMID- 22611731
TI  - The next stage. How to cope when your young adult leaves home.

PMID- 22611732
TI  - Bon voyage. How to prep smart, pack light, and stay safe.

PMID- 22611733
TI  - Happy campers. ADA Diabetes Camps create bonds that last a lifetime.

PMID- 22611734
TI  - Doctor is in. Ask this endo about his A1C--he just might tell you.

PMID- 22611735
TI  - Insurances. A guide to health plan lingo.

PMID- 22611736
TI  - Crunch!

PMID- 22611737
TI  - Portions perfected. How to rightsize what you eat in a supersize world.

PMID- 22611738
TI  - Nail cosmetics.

PMID- 22611739
TI  - What is your diagnosis? Angiosarcoma arising in the eyelid.

PMID- 22611740
TI  - What's eating you? The sticktight flea (Echidnophaga gallinacea).

PMID- 22611741
TI  - Premature hair graying.
AB  - Hair pigmentation and graying are important topics for the understanding of the
      physiology of aging; the differentiation of stem cells; and the mechanisms
      underlying disease processes such as progeroid syndromes, vitiligo, and
      hypothyroidism. Although hair graying, or canities, is a common process occurring
      in people as they age, an unknown percentage of individuals experience premature
      graying from familial inheritance or pathologic conditions. We review the
      physiology of hair pigmentation and the mechanism underlying physiologic graying,
      and we explore the etiology of pathologic causes of premature graying,
      pathologies associated with premature graying, and the limited available
      treatment options for hair graying.

PMID- 22611742
TI  - Cutaneous mucormycosis: a case report.
AB  - Cutaneous mucormycosis is a rare opportunistic fungal infection. It usually is
      benign in immunocompetent patients, but it can lead to devastating consequences
      in immunocompromised patients. Immediate diagnosis and treatment are crucial in
      preventing fatality. We describe a case of cutaneous mucormycosis in a man with a
      history of non-Hodgkin lymphoma in an effort to raise diagnostic suspicion of
      this life-threatening infection and prevent a fatal outcome.

PMID- 22611743
TI  - Gianotti-Crosti syndrome: a case report in an adult.
AB  - Gianotti-Crosti syndrome (GCS) is a viral-associated eruption that most commonly
      occurs in children aged 15 months to 2 years. It consists of monomorphic red
      brown to pink papules and vesicles distributed symmetrically on the cheeks,
      extensor surface of the extremities, and buttocks. The eruption usually
      spontaneously resolves over the course of 10 to 60 days. We report the rare case
      of GCS in an adult. An otherwise healthy 20-year-old woman presented with a
      pruritic eruption of 2 weeks' duration on the dorsal aspect of her hands and
      feet, elbows, and knees. The patient received oral corticosteroids prior to
      presentation to our clinic with some improvement. A biopsy revealed
      histopathologic findings consistent with a diagnosis of GCS. The patient's
      aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were
      elevated. Over the course of the next 2 months, the patient's skin findings
      completely resolved with normalization of liver function tests. The clinical and
      histologic correlation was consistent with GCS in an adult. This condition may
      not be as rare in adults as previously thought. Clinicians should keep GCS in
      their differential diagnosis when examining adult patients.

PMID- 22611744
TI  - Drug hypersensitivity reactions presenting as a morbilliform eruption with
      islands of sparing.

PMID- 22611745
TI  - Primary cutaneous infection by Mycobacterium avium: a case report and literature
      review.
AB  - Nontuberculous mycobacteria (NTM) are becoming increasingly important cutaneous
      pathogens as the number of susceptible patients increases. Nevertheless, primary
      cutaneous infection by one particular species, Mycobacterium avium complex (MAC),
      remains relatively unusual, particularly in immunocompetent patients. We review
      the English-language literature on primary cutaneous MAC in patients who were
      neither immunocompromised nor pharmacologically immunosuppressed. We offer an
      additional report of a healthy patient who presented to our clinic with primary
      cutaneous MAC following seemingly innocuous trauma to the leg.

PMID- 22611746
TI  - Drug rash with eosinophilia and systemic symptoms (DRESS syndrome).

PMID- 22611747
TI  - Subacute cutaneous lupus erythematosus: a case report of Polypodium leucotomos as
      an adjuvant therapy.
AB  - Subacute cutaneous lupus erythematosus (SCLE) is an uncommon autoimmune disease
      that results in substantial photosensitivity of affected patients. Eruptions
      often are triggered or exacerbated by UV light (UVL) exposure. We present a case
      of a patient with SCLE who was moderately controlled with hydroxychloroquine
      sulfate but achieved near total remission of disease after the addition of oral
      Polypodium leucotomos supplement which has photoprotective effects on human
      keratinocytes. We report sustained clinical response with the use of P leucotomos
      in lupus and suggest that it may have future application in photosensitizing
      dermatoses.

PMID- 22611748
TI  - Combination therapy with infliximab and methotrexate in recalcitrant
      mucocutaneous Behcet disease.
AB  - Behcet disease is a multisystem inflammatory disease with features of vasculitis.
      It undergoes periods of spontaneous remission and relapse. It often affects the
      skin, blood vessels, central nervous system, joints, gastrointestinal system,
      eyes, mucous membrane, and other systems, and it can cause substantial morbidity
      and mortality. The etiology of Behcet disease remains unknown. Current treatment
      of Behcet disease involves symptomatic relief with prevention of relapse. We
      describe the treatment of a recalcitrant case of Behcet disease with infliximab
      and methotrexate. The patient is a 40-year-old Korean woman with tender lesions
      on the lower extremities of 1.5 years' duration and intermittent oral and genital
      ulcerations that failed multiple conventional therapies. The patient was placed
      on a trial of infliximab. She reported resolution of the tender lower extremity
      lesions and the oral and vaginal ulcerations shortly after the initiation of the
      anti-tumor necrosis factor agent. The patient was symptom free for 2 years
      following the initiation of infliximab. She subsequently reported mild
      breakthrough oral ulcers and joint pain. The treatment regimen was modified by
      adding methotrexate 7.5 mg weekly, prednisone 5 mg daily, and a shortened
      treatment interval of infliximab infusion that resulted in resolution of her
      symptoms.

PMID- 22611749
TI  - Eosinophilic cellulitis (Wells syndrome) in a pediatric patient: a case report
      and review of the literature.
AB  - We report a 4-year-old boy who presented with multiple pruritic, annular,
      erythematous plaques on the lower extremities of 1 week's duration.
      Histopathology of an affected area revealed a dense dermal infiltrate of
      eosinophils and flame figures without evidence of vasculitis. A diagnosis of
      eosinophilic cellulitis (EC), or Wells syndrome, was made. The patient had an
      excellent response to topical and systemic steroids following 1 week of
      treatment. This case appeared to be idiopathic, as there was no cause identified
      such as arthropod bites or tinea infection. The patient's EC cleared and has not
      had a recurrence.

PMID- 22611750
TI  - Survey of demographic and educational factors among dermatology chairs and
      chiefs.
AB  - We surveyed 107 chairs and chiefs of US dermatology programs regarding
      demographic and educational factors. Of the 69 (64%) participants who returned
      completed surveys, 59 (86%) were men and 10 (14%) were women. We compared our
      data from chairs and chiefs to the US dermatology workforce and found that the
      chairs and chiefs were significantly more likely to be older men who were board
      certified in other fields, trained in dermatopathology and specialized in Mohs
      micrographic surgery (P < .001). Many chairs and chiefs also actively
      participated in research and held advanced degrees in addition to doctor of
      medicine.

PMID- 22611751
TI  - Quantitative microscopy in murine models of lung inflammation.
AB  - OBJECTIVE: To develop a quantitative means to measure lung inflammation using the
      murine models of chronic asthma and cystic fibrosis (CF). STUDY DESIGN:
      Translational-based medicine often utilizes animal models to study new and
      innovative therapeutics. In asthma and CF, the animal models focus on airway
      inflammation and remodeling. The asthma model is based on hypersensitivity
      induced airway disease, whereas the CF model focuses on the inflammatory response
      to infection with Pseudomonas aeruginosa. Qualitative measures of inflammation
      and lung pathophysiology introduce significant variability and difficulty in
      interpreting interventional outcomes. The highly sensitive and reproducible
      quantitative computational program interfaced with Image Pro Microscopy to
      monitor changes in lung inflammation and lung pathophysiology. The software
      interfaces with image microscopy and automates the lung section review process.
      RESULTS: Results from this program recapitulated data obtained by manual point
      counting of inflammation, bronchoalveolar lavage differential, and histology. The
      data show a low coefficient of variation and high reproducibility between slides
      and sections. CONCLUSION: Utilization of this new microscopy program will enhance
      the quantitative means of establishing changes in lung structure and inflammation
      as a measure of therapeutic intervention with the ability of refining
      interpretation of in vivo models potentially short-circuiting translation into
      the clinical setting.

PMID- 22611752
TI  - Differential diagnosis of follicular cancer and follicular adenoma using an
      expert system based on a set of qualitative signs of cell atypia.
AB  - OBJECTIVE: To determine the efficiency of the developed expert system based on a
      set of qualitative signs of cell atypia and their weighting coefficients in the
      differential diagnosis of follicular cancer and follicular adenoma of the thyroid
      gland. STUDY DESIGN: Sixty cytologic preparations of patients with histologic
      diagnosis of a follicular cancer and follicular adenoma were investigated.
      RESULTS: Weighting coefficients for each sign of atypia for both forms of
      pathology have been calculated with the help of the deduced equation. This
      allowed creating an expert system by which the function of transforming
      qualitative signs of cell atypia to a quantitative form was realized. "Strength
      reserve" according to the diagnostic index value, coincidence of the verified
      diagnosis with the histologic conclusion, and its invariability for all 12
      iterations testified to the reliability of an expert system. Preliminary trials
      showed the efficiency of an expert system for differentiating the nature of a
      thyroid follicular tumor to be 97.5%. CONCLUSION: The developed expert system
      allows high efficiency in making a differential diagnosis of thyroid follicular
      cancer and follicular adenoma.

PMID- 22611753
TI  - Discrimination between benign and malignant prostate biopsies using three
      dimensional chromatin texture analysis by confocal laser scanning microscopy.
AB  - OBJECTIVE: To evaluate the clinical usefulness of computing three-dimensional (3
      D) nuclear texture features on prostate biopsy specimens to discriminate among
      benign, prostatic intraepithelial neoplasia (PIN), and malignant specimens. STUDY
      DESIGN: Twelve prostate cancer biopsy specimens were selected, diagnosed as
      either benign (N = 4), PIN (N = 4), or malignant (N = 4). Sections 14 microm
      thick were stained. 3-D image stacks of selected benign and malignant areas were
      obtained by confocal laser scanning microscopy (CLSM) and analyzed off-line using
      in-house-developed software for 3-D semiautomated segmentation and calculation of
      texture features. The power of the 3-D texture features to discriminate among the
      pooled benign (N = 1,507), PIN (N = 673), and malignant nuclei (N = 1,251) was
      established by multivariate linear discriminant analysis. RESULTS: A total of
      68.8% of the benign nuclei, 77.2% of the PIN nuclei, and 78.5% of the malignant
      nuclei could be classified correctly after cross validation. CONCLUSION:
      Quantification of changes in the distribution of nuclear chromatin by means of 3
      D texture feature computation on CLSM images allows discriminating most benign
      and malignant prostate nuclei, which could be useful in cases that are difficult
      to diagnose morphologically.

PMID- 22611754
TI  - Cytogenetic abnormalities in exfoliated oral mucosal cells and their association
      with oral cancer.
AB  - OBJECTIVE: To assess cytogenetic abnormalities through quantification of
      micronuclei, broken eggs, and karyorrhexis, in cells from normal oral mucosa of
      individuals exposed to carcinogens (alcohol and tobacco) and adjacent to
      leukoplakias and squamous cell carcinomas. STUDY DESIGN: The sample was composed
      of 40 subjects aged > 30 years, divided into four groups: control,
      alcohol/tobacco, leukoplakia, and squamous cell carcinoma. For control and
      alcohol/tobacco groups, cells were collected from lower lip, tongue border, and
      floor of the mouth. For leukoplakia and squamous cell carcinoma groups, mucosa
      contralateral and adjacent to the lesions were analyzed. Cytologic smears were
      stained with the Feulgen reaction. A blind observer analyzed 1,000 cells per
      slide to quantify micronuclei, broken eggs, and karyorrhexis. RESULTS: The
      leukoplakia group showed an increased number of micronuclei compared to controls
      (p = 0.0016) and the alcohol/tobacco group (p = 0.0048) and also increased broken
      eggs compared to the alcohol/tobacco group (p = 0.0172). Similarly, the carcinoma
      group presented more micronuclei compared to controls (p = 0.0462) and more
      broken eggs compared to the alcohol/tobacco group (p = 0.0104). CONCLUSION: The
      assessment of cytogenetic abnormalities micronuclei and broken eggs may be useful
      for monitoring individuals exposed to risk factors for developing oral cancer.

PMID- 22611755
TI  - Expression of MUC1 (Ma695) in noninvasive papillary urothelial neoplasm according
      to the 2004 World Health Organization classification of the noninvasive
      urothelial neoplasm. An immunologic tool for the pathologist?
AB  - OBJECTIVE: To examine the association between MUC1 (Ma695) and noninvasive
      papillary urothelial neoplasm according to the 2004 World Health Organization
      classification. STUDY DESIGN: Histologic evaluation was performed in 46 patients
      with nontumoral benign bladder urothelium (n = 11), papillary urothelial neoplasm
      of low malignant potential (PUNLMP) (n = 14), low-grade papillary urothelial
      carcinoma (LgPUC) (n = 11), and noninvasive high-grade papillary urothelial
      carcinoma (HgPUC) (n = 10). Classical morphologic description and
      semiquantitative digital measurement were performed from immunohistochemical
      stained slides using an anti-MUC1 antibody (Ma695). RESULTS: Measures showed an
      obvious statistical difference between benign urothelium and LgPUC (p = 0.0004)
      or HgPUC (p = 0.0041). MUC1 is expressed less in PUNLMP than in LgPUC (p = 0.04).
      Benign urothelium and PUNLMP more often showed apical and superficial MUC1
      expression. Basal cells with cytoplasmic and/or circumferential membrane
      positivity were more often observed in LgPUC and HgPUC (p < 0.001). CONCLUSION:
      MUC1 could be an interesting tool for the pathologist to differentiate between
      PUNLMP and LgPUC or HgPUC.

PMID- 22611756
TI  - Combined expression of p161NK4a and p27Kip1, but not p21WAF1, differentiates
      endocervical from endometrial adenocarcinoma.
AB  - OBJECTIVE: To differentiate endocervical adenocarcinoma (ECA) from endometrial
      adenocarcinoma (EMA) using p16INK4a, p21WAF1 and p27Kip1. STUDY DESIGN: The
      distinction between ECA and EMA can be problematic on small biopsies or in
      advanced tumor stage. Immunohistochemistry was done on paraffin-embedded tissue
      sections of hysterectomy specimens of all types of ECA and EMA. Protein
      expression was scored as 0 to 3 depending on percentage of positive tumor cells.
      RESULTS: A total of 40 ECA and 92 EMA cases were examined. For ECA, 32 of 40
      (80.0%) cases had score of 3 with p16INK4a expressions; 23 of 92 (25.0%) cases of
      EMA had similar scores. For p21WAF1 expressions, 28 of 40 (70.0%) ECA cases
      scored 3 and 72 of 82 (78.2%) of EMA had a similar score. p27Kip1 scored 3 in 17
      of 40 (42.5%) ECA cases; only 14 of 92 (15.2%) cases of EMA cases had such a
      score. We observed significant higher expressions of p16INK4a (p < 0.001) and
      p27Kip1 (p = 0.001) in ECA than in EMA. Combined positive expression and combined
      negative expression of p16INK4a and p27Kip1 strongly differentiates ECA from EMA
      (< 0.0001). CONCLUSION: ECA could be strongly differentiated from EMA based on
      the expressions of combined p16INK4a and p27Kip1.

PMID- 22611757
TI  - Simple flow cytometric protocol of CD4+/CD8+ lymphocyte ratio assessment in
      bronchoalveolar lavage fluids from patients with interstitial lung diseases.
AB  - OBJECTIVE: To validate the fast and accurate flow cytometric (FCM) protocol using
      blood-standardized antibodies for alveolar lymphocyte subtyping with respect to
      standard immunocytochemistry (IC). STUDY DESIGN: FCM and IC were applied to
      immunophenotype T cell subsets in bronchoalveolar lavage (BAL) fluids from
      patients with interstitial lung diseases. Diagnostic BAL specimens from 50
      patients with suspected sarcoidosis, idiopathic pulmonary fibrosis, and
      hypersensitivity pneumonitis were evaluated by both IC and FCM. In FCM, CD4+ and
      CD8+ T cells were identified by light scatter gating with CD3 selection using
      basic tricolor cytometer. RESULTS: Relative amounts of CD4+, CD8+ T cells, and
      CD4+/CD8+ ratios demonstrated by the FCM showed excellent, significant
      correlations with IC results. FCM values did not differ significantly from IC
      results. However, the sensitivity and specificity of conventional IC staining
      were not sufficient to assess CD4+/ CD8+ ratio in most idiopathic pulmonary
      fibrosis cases. Additionally, performing IC immunophenotyping in BAL samples with
      low lymphocyte content introduced a remarkable error into CD4+/CD8+ ratio
      assessment. CONCLUSION: FCM allowed reliable, precise, and fast T-cell subset
      measurement in all BAL samples, overcoming the IC disadvantages. Our validated
      FCM protocol provides diagnostically relevant CD4+/CD8+ ratio determination by
      simple light scatter gating strategy with CD3 selection.

PMID- 22611758
TI  - Nasopharyngeal nonkeratinizing (undifferentiated) monstrous cell carcinoma. A
      case report.
AB  - BACKGROUND: The histologic type of nasopharyngeal carcinoma can be an important
      factor in the prognosis. The effects, if any, of the degree of cellular
      pleomorphism is uncertain. CASE: In this report, we present a case of
      nonkeratinizing, undifferentiated nasopharyngeal carcinoma with monstrous tumor
      giant cells. An extremely high level of aneuploidy and dense cytoplasmic
      accumulation of Epstein-Barr virus capsid antigen were found in tumor cells. The
      patient was treated with concomitant chemoradiotherapy. CONCLUSION: Nine years of
      follow-up with no recurrences suggests that this extreme morphologic variation
      may impart no adverse prognostic effect.

PMID- 22611759
TI  - Epigenetic therapy in cancer: perspective and paradoxes.

PMID- 22611760
TI  - Cell proliferation and apoptosis in prostate needle biopsies with adenocarcinoma
      Gleason score 6 or 7.
AB  - OBJECTIVE: To analyze whether cell proliferation and apoptotic indexes in needle
      biopsies with prostate cancer Gleason 6 or 7 can identify more objectively
      Gleason score 6 or 7 in needle biopsy samples. STUDY DESIGN: Seventy patients
      diagnosed by needle biopsy and treated by radical prostatectomy were included.
      Fifty cases were Gleason score 6 and 20 were Gleason 7. Twenty-two cases were
      organ-confined and 48 nonorgan-confined. Histologic sections from needle biopsies
      were stained for cell proliferation using the MIB 1 (Ki67) antibody and in situ
      end-labeling technique for apoptosis and recorded as the percentage of positive
      cells. Statistical analysis included Student's t-test, Pearson's test, and
      logistic regression analysis. RESULTS: We found increased apoptotic and
      proliferation indexes from Gleason 6 to 7, and from organ-confined to non-organ
      confined. Apoptotic index was not associated to stage or Gleason score. We
      identified an association between cell proliferation and Gleason score indicating
      that higher proliferation index is associated with a higher probability of
      presenting a Gleason score 7. There was no association between pathologic stage
      and cell proliferation. CONCLUSION: Cell proliferation and apoptosis can
      distinguish a subset of aggressive lesions in needle biopsies with Gleason 6 or 7
      prostate adenocarcinoma.

PMID- 22611761
TI  - Quantitative image analysis of gamma-H2AX foci induced by ionizing radiation
      applying open source programs.
AB  - OBJECTIVE: To test a CellProfiler pipeline for automated counting and
      characterization of gamma-H2AX foci in color images of human cultured cells.
      STUDY DESIGN: A431 cells were irradiated and stained for gamma-H2AX foci
      detection. Sets of color images were analyzed visually, and findings were
      compared with those using FociCounter and CellProfiler software. RESULTS: The
      CellProfiler pipeline includes some proprieties not present in FociCounter, such
      as the automatic detection of nuclei, the detection of touching nuclei and the
      rejection of nuclei that touch the border of the image. The time required for
      manual operation is associated with the number of images analyzed visually or by
      FociCounter but not for the CellProfiler program. CellProfiler reduced manual
      operation time and is about 4 times faster than semiautomatic detection using
      FociCounter and 10 times faster than visual counting. CONCLUSION: We conclude
      that CellProfiler and FociCounter are reliable tools for measuring gamma-H2AX
      foci. However, CellProfiler overcomes the limitations of the FociCounter program
      and is able to detect nuclei automatically, saving considerable manual operation.

PMID- 22611762
TI  - Maspin expression is a favorable prognostic factor in non-small cell lung cancer.
AB  - OBJECTIVE: To evaluate prognostic impact of maspin expression in patients with
      resected non-small cell lung cancer (NSCLC). STUDY DESIGN: From 1996 to 2001, 439
      patients underwent radical surgery for NSCLC at the Polytechnic University of the
      Marche Region. Maspin expression was detected as cytoplasmic and nuclear staining
      of neoplastic cells. For cytoplasmic staining, cases were classified as negative,
      low positive, and high positive. In positive cases, intensity of staining was
      also considered and scored. A similar classification was used for nuclear
      staining, but intensity was not considered. RESULTS: The analysis showed that
      smoking history, pathologic stage of disease, N status, histologic grading, sex,
      and Eastern Cooperative Oncology Group performance status had a prognostic impact
      on overall survival (OS). Expression of maspin was also found to be an
      independent prognostic factor. A statistically significant longer OS was seen in
      patients with higher compared with lower expression of nuclear maspin, and poorer
      OS was present in patients with a higher intensity of cytoplasmic staining.
      Nuclear expression of maspin was also found to be an independent prognostic
      factor at multivariate analysis. CONCLUSION: Results suggest that overexpression
      of maspin correlates with favorable prognosis in NSCLC. and may be a useful
      clinical marker.

PMID- 22611763
TI  - Osteopontin expression in chronic plaque psoriasis: an association with the
      severity of disease.
AB  - OBJECTIVE: To explore the possible role of osteopontin (OPN) in chronic plaque
      psoriasis and understand the role of inflammation in psoriasis. STUDY DESIGN: We
      investigated 36 patients with chronic plaque psoriasis using immunohistochemical
      technique for evaluation of OPN immunolocalization compared to normal skin
      biopsies of 10 normal subjects representing the control group. RESULTS: OPN was
      expressed in the epidermis of all specimens, both in the psoriasis group and the
      control group without any significant differences except for the tendency of
      psoriatic lesions to show more cytoplasmic and nuclear pattern of OPN staining
      (55.56%) compared to normal skin (20%). Epidermal strong and diffuse
      immunostaining of OPN was associated with the severity of psoriasis, and there
      was a correlation of the intensity of OPN expression with the density of the
      dermal inflammatory infiltrate. CONCLUSION: Our study suggests that OPN is
      involved in the pathophysiology of psoriasis, and a possible association with
      disease severity. OPN acts by different mechanisms through its expression by
      lesional keratinocytes, inflammatory cells, and endothelial cells. Nuclear
      localization of OPN may have a more significant role in the pathogenesis of
      psoriasis.

PMID- 22611764
TI  - Differential diagnosis of follicular tumor by expert systems based on a set of
      quantitative features of thyrocyte nuclei and aggregates.
AB  - OBJECTIVE: To develop expert systems for classification of follicular thyroid
      tumor at a preoperative stage. STUDY DESIGN: Fine needle aspiration biopsy of the
      thyroid gland with a histologic conclusion of follicular cancer and follicular
      adenoma were the object of the morphometric study. General sample size was 4500
      nuclei and 3000 aggregates. RESULTS: Quantitative regularities of pathologic
      changes in thyrocyte nuclei and aggregates in follicular cancer and follicular
      adenoma were revealed. Threshold values and weighting coefficients of
      quantitative features of thyrocyte nuclei and aggregates characterizing cancer
      made the basis of the two expert systems. Expert systems included standard 2-D S
      matrix containing threshold values of nuclei and aggregates in cancer and their
      weighting coefficients as well as 1-D scientific X-matrix designed for filling
      with quantitative features of the studied object. The diagnosis was verified by
      the value of a diagnostic index by means of comparing feature values in the
      corresponding elements of S- and X-matrices. After that, a diagnostic index was
      calculated taking into account the features' weighting coefficient. CONCLUSION:
      The developed expert systems based on a set of quantitative features of thyrocyte
      nuclei and aggregates will allow assessing the malignant potential of a
      follicular thyroid tumor at a preoperative stage.

PMID- 22611765
TI  - Prostate cancer gene 3 urine assay cutoff in diagnosis of prostate cancer: a
      validation study on an Italian patient population undergoing first and repeat
      biopsy.
AB  - OBJECTIVE: To determine an optimal prostate cancer gene 3 (PCA3) cutoff in
      predicting prostate cancer in Italian patients undergoing first or repeat biopsy.
      STUDY DESIGN: In this observational multicenter study 1246 men with elevated
      prostate specific antigen (PSA) and negative digital rectal examination, with
      prostate biopsy after PCA3 assessment, were divided into two groups submitted to
      PCA3 testing before or after previous negative biopsies. Ideal PCA3 cutoff was
      identified using area under the curve of the receiver operating characteristic
      analysis. Various cutoff values were used to determine the best predictive score.
      Univariate and multivariate logistic regression models compared age, PSA, free
      PSA, and PCA3 score to predict prostate cancer. RESULTS: PCA3 cutoff 39-50 had
      the highest accuracy in the repeat biopsy group in which cutoff of 39 could have
      avoided 51.9% negative repeat biopsies, eventually missing 7.8% of cancers (all
      low risk); cutoff of 50 would have prevented 56.5% of negative repeat biopsies,
      missing 29 tumors (10.3%), 5 potentially aggressive. The PCA3 test performed
      poorly in the first biopsy group. CONCLUSION: We confirm the usefulness of PCA3
      in Italian men with a previous negative biopsy. We achieved the best performance
      at a cutoff of 39. PCA3 did not perform better than PSA in non-biopsy-selected
      men.

PMID- 22611766
TI  - Multifractal spectrum differentiation of well-differentiated adenocarcinoma from
      complex atypical hyperplasia of the uterus.
AB  - OBJECTIVE: To introduce a new field of multifractal spectrum in distinguishing
      between endometrial well-differentiated adenocarcinoma (WDAC) and complex
      atypical hyperplasia (CAH). STUDY DESIGN: Thirteen cases of CAH and 16 of WDAC
      were selected from radical hysterectomy specimens, and multifractal spectrum was
      measured from at least 4-5 representative digitized images of each case. The data
      were collected from f(alpha) vs. alpha curves. The values of alpha max, alpha
      min, and their difference delta alpha (alpha max-alpha min) were recorded and the
      data compared. RESULTS: The mean +/- SD of alpha max, alpha min, and delta alpha
      of CAH were 2.36357 +/- 0.111623, 1.71357 +/- 0.032160, and 0.64214 +/- 0.094248,
      respectively. The mean +/- SD of alpha max, alpha min, and delta of WDAC were
      2.50640 +/- 0.104545, 1.72100 +/- 0.036436, and 0.77620 +/- 0.108268,
      respectively. The mean of alpha max, alpha min, and delta alpha of WDAC were
      higher than in CAH. Mann-Whitney U test showed significant difference (p <
      0.0001) of alpha max and delta alpja of WDAC and CAH. CONCLUSION: Multifractal
      dimension is significantly different in WDAC and CAH. The multifractal dimension
      is a new area in pathology. This study demonstrates the potential usefulness of
      multifractal analysis in histopathology.

PMID- 22611767
TI  - From biopsy to active surveillance in small renal masses: is it feasible?

PMID- 22611768
TI  - Protect our jobs! Protect our voice! Workers stand up against attacks on our
      collective bargaining rights.

PMID- 22611769
TI  - As I see it.

PMID- 22611770
TI  - Safe patient care.

PMID- 22611771
TI  - Safe patient care--it's time!

PMID- 22611772
TI  - A move toward the future for Michigan's health.

PMID- 22611773
TI  - Thoughts on transparency--and a few final words.

PMID- 22611774
TI  - Medicine and the media, both incredible and frightening.

PMID- 22611775
TI  - Medicine and the media.

PMID- 22611776
TI  - PHP: outreach to physicians broadens.

PMID- 22611777
TI  - TMA: the view from 40,000 feet (40 years), Part I.

PMID- 22611778
TI  - Patient portals: improving outcomes, increasing efficiencies.

PMID- 22611779
TI  - Efficiency and freedom through mobile devices.

PMID- 22611780
TI  - Coexistence of systemic lupus erythematosus and thrombotic thrombocytopenic
      purpura: a case report.
AB  - Systemic Lupus Erythematosus (SLE) and Thrombotic Thrombocytopenic Purpura (TTP)
      are two different clinical entities that can have overlapping features. Early
      recognition of either disease is vital since therapy differs. The exact incidence
      of coexistence of SLE and TTP is unclear. Rituximab has recently been used in the
      treatment of plasmapheresis-resistant TTP and is effective when SLE and TTP
      present together. We report a case of a 52-year-old female who presented with
      both SLE and TTP, years after she had initially presented with TTP alone. During
      this episode she did not respond to the conventional treatment with
      plasmapheresis and steroids. She was subsequently started on rituximab and
      responded well.

PMID- 22611781
TI  - A young male with coexisting astrocytoma and renal cell carcinoma.
AB  - Familial cancer syndrome is a genetic condition that causes an individual to be
      at increased risk for specific types of cancers. There are different familial
      cancer syndromes, each of which is associated with a specific set of
      characteristic cancers. Atypical presentations such as the combination of two
      types of cancers involving the same primary site with a slightly different
      pathology are not uncommon. The reason for such a high degree of phenotypic
      variation could be due to somatic mosaicisms which, although rare, have been
      reported in association with some of the familial cancer syndromes. We report a
      case of a 44-year-old Caucasian male with coexisting astrocytoma and Renal Cell
      Carcinoma (RCC), in whom the diagnosis of Von Hippel-Lindau (VHL) syndrome was
      considered. Although the patient tested negative for the classic VHL gene, the
      possibility of somatic mosaicism could not be ruled out. This case reflects the
      importance of having a high index of suspicion to screen the patients with more
      than one type of malignancies for familial cancer syndrome, as it may present
      with atypical features and the diagnosis of familial cancer syndrome has
      important implications in genetic counseling.

PMID- 22611782
TI  - Atypical presentation of pericarditis.

PMID- 22611783
TI  - The robust exchanges of views in the letters section of the February/March 2012
      (Volume 58, Number 1) edition of the Journal of the Irish Dental Association.

PMID- 22611784
TI  - Quiz. Orthodontic facemask/protraction face mark used for early treatment of
      skeletal Class III malocclusion with protraction therapy.

PMID- 22611785
TI  - Change needed.

PMID- 22611786
TI  - IDA seeks to end confusion on fruit juice advice.

PMID- 22611787
TI  - Who can inspect your dental practice?
AB  - There are several government agencies that may inspect your dental practice. The
      majority of inspections are carried out by the National Employment Rights
      Authority, the Health and Safety Authority, the Revenue Commissioners and the
      Radiological Protection Institute of Ireland. Below is a summary of the minimum
      requirements that should be in place to ensure compliance with the relevant
      legislation. You should always seek appropriate advice for your own particular
      circumstances.

PMID- 22611788
TI  - Mouth cancer awareness: what's at stake?

PMID- 22611789
TI  - RPII inspections in the dental sector.

PMID- 22611790
TI  - Endodontic-periodontal management of a maxillary lateral incisor with an
      associated radicular lingual groove and severe periapical osseous destruction--a
      case report.
AB  - Radicular lingual grooves are morphological defects, which are found most
      frequently in maxillary anterior teeth and are a predisposing factor for
      periodontal disease. They are easily overlooked as aetiologic factors, as these
      grooves are covered by periodontal tissues. This case report presents a
      successful management of a case of a maxillary lateral incisor with an associated
      radicular lingual groove and severe periapical osseous destruction in a 30-year
      old female patient. A combination of endodontic treatment, radiculoplasty to
      eliminate the radicular lingual groove, and periapical surgery to eliminate the
      periapical osseous defect was used. At two-year follow-up, the patient was
      comfortable and complete resolution of the periapical pathology was evident.

PMID- 22611791
TI  - Outcomes from the first mouth cancer awareness and clinical check-up day in the
      Dublin Dental University Hospital.
AB  - PURPOSE OF THE STUDY: To increase public awareness about mouth cancer, the Dublin
      Dental University Hospital (DDUH) hosted an awareness day and free mouth check-up
      in September 2010. The messages of information, self-examination and risk
      management, and the importance of early detection, were available to all
      attendees. The role of general dental and medical practitioners in examination of
      the mouth was stressed. MATERIAL AND METHODS: A questionnaire regarding knowledge
      about the causes of and risk factors for mouth cancer, and a clinical check-up,
      were completed. RESULTS: A total of 1,661 individuals (675 male, 986 female) were
      examined. The mean age was 59.6 years. Just over one-third (36.5%) of those
      examined required no action, and slightly less (30%) were advised to return to
      their general dental or medical practitioner (GDP/GMP). Some 21% were advised
      about self-examination of the mouth, and 8% about smoking cessation. Of the
      remainder, 52 people (3.5%) were sent for a second opinion. Of these, 30
      individuals were referred for further investigation, including biopsy in 27
      cases. Following biopsy, five individuals were diagnosed with carcinoma in situ
      or carcinoma. CONCLUSIONS: The diagnosis of five people with mouth cancers, who
      may not otherwise have been identified for early treatment, highlights the need
      for regular mouth examination. It is inappropriate that such an exercise would
      remain the preserve of the dental teaching hospitals, and it is vital that all
      dentists take on the responsibility for regular mouth checks for all of their
      patients. More should be done to encourage those identified as high risk to visit
      their dentist. There is a need for recognition of the additional resources
      required for the detection and timely management of such cancers.

PMID- 22611793
TI  - But I've always done it that way!

PMID- 22611792
TI  - The development of mouth, head and neck cancer awareness in Ireland and results
      of Mouth Cancer Awareness Day 2011.

PMID- 22611794
TI  - Locking the screw after rapid palatal expansion: A superfluous procedure?

PMID- 22611795
TI  - Class II treatment of an adolescent patient with a history of acute lymphocytic
      leukemia.

PMID- 22611796
TI  - A modified Theroux Phase I retainer design.

PMID- 22611797
TI  - 2011 JCO orthodontic practice study. Part 3 Practice growth and staff data.

PMID- 22611798
TI  - Non-surgical uprighting of mesially impacted lower molars.

PMID- 22611799
TI  - A new self-ligating lingual bracket with square slots.

PMID- 22611800
TI  - ADA must challenge false claims of dental therapist advocates.

PMID- 22611801
TI  - Learn a lesson from the veterinarian profession.

PMID- 22611802
TI  - The 12 points of the dental law.

PMID- 22611803
TI  - Ready for an office makeover?

PMID- 22611804
TI  - Community leaders work to solve lack of access to oral healthcare.

PMID- 22611805
TI  - Does your office have a personality?

PMID- 22611806
TI  - Learn lessons from dental malpractice cases.

PMID- 22611807
TI  - Barry Booth creates a smile for a lifetime.

PMID- 22611808
TI  - Top five tips for caring for an infant's primary teeth.

PMID- 22611809
TI  - Labor reforms.

PMID- 22611810
TI  - A home for births.

PMID- 22611811
TI  - Delivery specialists.

PMID- 22611812
TI  - Women's work?

PMID- 22611813
TI  - Risk and reward.

PMID- 22611814
TI  - Bringing home baby.

PMID- 22611815
TI  - Through a different lens.

PMID- 22611816
TI  - Hard choices that living requires.

PMID- 22611817
TI  - Twenty-first century women's health care.

PMID- 22611818
TI  - Reassessing hysterectomy.
AB  - Hysterectomy is widely used for treating a variety of gynecologic conditions.
      Most hysterectomies are elective and are performed to treat benign indications
      for which there are other effective alternatives. Observational studies are
      increasingly highlighting the effects of hysterectomy and concomitant
      oophorectomy on a variety of long-term health outcomes including fracture risk,
      pelvic floor dysfunction, all-cause mortality, cardiovascular disease, and
      neurologic function. Individualizing therapy and discussing appropriate
      alternatives to hysterectomy is an important responsibility for all health care
      providers.

PMID- 22611819
TI  - Recognizing and treating ovarian cancer.
AB  - Ovarian cancer is the fifth-leading cause of cancer-related death among women and
      is the deadliest gynecologic cancer. The mortality rate associated with this
      disease is attributed in part to the fact that it is often not diagnosed until
      its later stages. Although no definitive screening test for this form of cancer
      yet exists, a recent consensus statement offers guidance to help physicians
      identify women who may have the disease. This article describes the importance of
      and means for early diagnosis of ovarian cancer, reviews treatments, and
      discusses the role of both the primary care physician and the gynecologic
      oncologist with regard to this disease.

PMID- 22611820
TI  - The evolution of minimally invasive gynecologic surgery.
AB  - Since the 1980s, minimally invasive procedures have made inroads into gynecologic
      surgery. This article describes the progression of technological developments
      that have led gynecologists to attempt and master more and more minimally
      invasive surgical techniques over the last 30 years. It describes the minimally
      invasive gynecologic surgeries that are done today and reviews evidence that
      shows these procedures lead to faster recovery, fewer complications, and better
      outcomes.

PMID- 22611821
TI  - Safe and individualized labor analgesia: A review of the current options.
AB  - Although some women want to experience childbirth without medications, most women
      in the United States labor with an epidural or spinal analgesic. Epidurals
      provide relatively consistent pain relief, are long-lasting, can be titrated
      according to the analgesic needs of the mother, and can be bolused for procedures
      such as forceps, vacuum, or cesarean delivery. But they can have undesirable side
      effects including lower-extremity motor block, hypotension, urinary retention,
      and pruritus, and they may increase the risk for a slightly prolonged labor, a
      forceps or vacuum delivery, and fever during labor. This article describes the
      current thinking regarding labor analgesia and how anesthesiologists and
      obstetricians can help women have a birth experience that is both safe and
      satisfying.

PMID- 22611822
TI  - Cost effectiveness in obstetrics and gynecology: The levonorgestrel intrauterine
      system.
AB  - Use of evidence-based practices that are both cost-effective and acceptable to
      patients is now a focus in health care. Considerable cost savings can be realized
      by reducing unintended pregnancies and improving control of menstrual-related
      morbidity. The levonorgestrel intrauterine system (LNG-IUS), often referred to by
      its brand name Mirena, has been approved by the Food and Drug Administration both
      for contraception and fortreating abnormal uterine bleeding. The device has been
      available in the United States since 2000 and has been used in Europe since 1990.
      Despite the fact that several evidence-based guidelines include use of the LNG
      IUS, it remains underutilized in this country. This article reviews the benefits
      of the LNG-IUS as they pertain to women's health and to the cost of health care.

PMID- 22611823
TI  - Reducing liability in obstetric care.

PMID- 22611824
TI  - [Image of the month: Voluntary ingestion of foreign bodies: Psychiatric aspects].

PMID- 22611825
TI  - [Constrictive pericarditis: case report and review].
AB  - Constrictive pericarditis (CP) is a common disease with difficult diagnosis. We
      report a well-documented case of CP with extended pericardial calcification
      treated by total pericardiectomy. A brief review of symptoms and signs of CP is
      presented, as well as additional examination allowing the diagnosis to be
      confirmed. The differential diagnosis with restictive cardiomyopathy is also
      discussed.

PMID- 22611826
TI  - [Contrast-enhanced ultrasound in hepatic focal nodular hyperplasia].
AB  - The ultrasound contrast agent is composed by microbubbles of sulfur hexafluoride.
      It is now recognized to the characterization of liver lesions. Focal nodular
      hyperplasia (FNH) is a benign lesion of the liver. It is found in the majority of
      cases among women with a sex ratio 1M/8F, no typical clinical presentation or
      malignancy is described. When the liver lesion was found in B-mode ultrasound,
      injection of contrast can be realized immediately by the radiologist. The study
      of the lesion during the arterial, portal and late phases with the contrast
      enhanced ultrasound allows the diagnosis of FNH with a specificity of 97%. In
      arterial phase, the prescence of a central artery and scarring, centrifugal
      progression of enhancement, a transient unenhanced zone and in portal and late
      phases, isoechogenicity compared to adjacent parenchyma are the main features of
      FNH described in the literature.

PMID- 22611827
TI  - [New European guidelines for the management of dyslipidaemia in cardiovascular
      prevention].
AB  - The new guidelines from the European Atherosclerosis Society and the European
      Society of Cardiology include a number of updated items. In this paper, we
      summarize 4 of these changes that we consider to be the most pertinent. Firstly,
      cardiovascular risk is now stratified according to 4 (previously 2) categories:
      "very high risk" (patients with cardiovascular disease, patients with diabetes >
      40 years old who have at least one other risk factor, patients with kidney
      failure, or patients in primary prevention with a SCORE value > or = 10%); "high
      risk" (patients in primary prevention with a SCORE value > or = 5% and < 10% or
      patients with a particularly serious risk factor such as familial
      hypercholesterolaemia or patients with diabetes < 40 years old without any other
      risk factor); "moderate risk" (primary prevention with SCORE > or = 1% and < 5%);
      and "low risk" (primary prevention with SCORE < 1%). The SCORE value for patients
      in primary prevention is estimated using the SCORE table (calibrated for
      Belgium). Risk in this table may now be corrected according to HDL cholesterol
      level. Secondly, the therapeutic targets for each category are now more
      stringent: LDL cholesterol < 70 mg/dl (or reduced by at least 50%) if the risk is
      "very high"; < 100 mg/dl if the risk is "high"; and < 115 mg/dl if the risk is
      "moderate". Thirdly, for patients at "high" or "very high" risk, particularly in
      patients with combined dyslipidaemia, two further therapeutic targets should be
      considered: non-HDL cholesterol and apolipoprotein B levels. Fourthly, the follow
      up of efficacy (lipid profile) and tolerance (hepatic and muscular enzymes) is
      described in more details so as to harmonize case management in clinical
      practice.

PMID- 22611828
TI  - [Does Radiotherapy have a role in end-of-life care?].
AB  - Up to 50% of cancer patients will receive radiation therapy as a part of their
      treatment. Radiation may be delivered with curative or palliative intent,
      according to the extent of disease, the patient's performance status and his
      wishes. The aim of palliative radiotherapy is to locally control primary tumor or
      metastasis and, thus, to slow down the disease. Another purpose is to decrease
      symptoms as part of the supportive care in the end of life. The total dose, the
      dose per fraction and the technique of irradiation used vary with the treatment
      aim. Indications of radiotherapy in the end of life are reviewed in this paper

PMID- 22611829
TI  - [Hypertension and diabetes: about a common but complex association].
AB  - Both diabetes mellitus and arterial hypertension are commonly observed in a
      single patient. However, the relationship between these two entities is rather
      complex and there is a great heterogeneity regarding the underlying
      pathophysiological mechanisms and the clinical presentations. These
      particularities may have important consequences from a therapeutic point of view,
      as far as blood pressure targets or even pharmacological strategies are
      concerned. The present article will discuss the various causes of hypertension in
      the different types of diabetes, the different forms of hypertension in the
      diabetic patient, the modalities of treating hypertension in presence of various
      specific complications (metabolic syndrome, coronary heart disease or renal
      impairment), and the specificities when hypertension is associated with diabetic
      cardiovascular autonomic neuropathy.

PMID- 22611830
TI  - [Drug-related psoriasis].
AB  - Psoriasis is a common genetic disorder that may be initiated (drug-induced
      psoriasis) or exacerbated (drug-triggered psoriasis) by some drug intakes. Beta
      blockers, lithium, some antimelarial drugs, non steroidal anti-inflammatory
      agents and tetracyclines are recognized to influence the clinical course of
      psoriasis. Other drugs are likely or possibly involved in this process.

PMID- 22611831
TI  - [The thousand and one facets of skin stem cells. The future has found new roots].
AB  - Multipotent stem cells of adult skin are found in distinct biological locations
      identified as niches. These stem cell populations are defined by specific
      molecular and functional attributes. The epidermal stem cells are found in the
      interfollicular areas and in the bulge and isthmus of the hair follicles. Dermal
      stem cells are harbored in the peripilar connective tissue sheaths and in the
      hair papilla. Some skin stem cells are found in extracutaneous sites. Other stem
      cells are involved in pathology, such as neoplastic stem cells identified in
      malignant melanomas.

PMID- 22611832
TI  - [Interferons and thyroid abnormalities: literature review].
AB  - Interferons are a large family of glycoproteins known as cytokines or substances
      released by lymphocytes that interfere with viral replication within host cells
      and activate the immune system. Nowadays, interferons are used as
      immunomodulators to treat many diseases, especially hepatitis. Among their side
      effects thyroidopathies are the most important. Their frequency varies from a
      study to another, and may reach 20%. Thyroid disorders may be an increase in
      thyroid antibodies or an abnormal function. Interferons can reveal or induce
      thyroid diseases whose mechanisms are still not understood. It seems that
      cytokines modify the immune system leading to an increase in stimulating or
      inhibiting antibodies production. A direct thyroid cells cytolysis is also
      possible. When stimulating antibodies are prevailing, hyperthyroidism is the
      resulting disease. This last situation is rarer than hypothyroidism resulting
      from an increase in inhibiting antibodies and/or thyroid cells cytolysis. When
      thyroid disease occurs under interferon therapy, overt hyper or hypothyroidism
      should be treated symptomatically without stopping interferons prescribed for a
      severe disease. However, after stopping interferons, control of thyroid function
      should be done to check if there is an ad integrum thyroid recovery.

PMID- 22611833
TI  - [Zoely, a combined oral contraceptive, monophasic pill containing estradiol and
      nomegestrol acetate].
AB  - A new combined oral contraceptive called Zoely has just been marketed in Belgium.
      It contains nomegestrol acetate, a progestin known for its high contraceptive
      reliability based on its antigonadotropic power and long half-life. This
      progestin is associated with estradiol and Zoely is devoid of ethinyl estradiol,
      which is the usual component of the majority of combined oral contraceptives and
      is primarily responsible for thrombotic side effects of the pill. The compositon
      and type of regimen of this new oral contraceptive contribute to its efficacy and
      excellent clinical tolerance.

PMID- 22611834
TI  - [Structured differential diagnosis of a transient impairment of consciousness].
AB  - Transient impairment of consciousness frequently prompts the patient to consult a
      neurologist or a cardiologist. Detailed medical history and physical examination
      allow to distinguish fainting from epileptic seizure, metabolic or psychogenic
      events. We report the history of an 83-year-old woman who presented a transient
      loss of consciousness.The vascular, investigation demonstrated a subocclusive
      stenosis of one of the internal carotid arteries. We shall consider the
      differential diagnosis of transient impairment of consciousness and discuss the
      relationship between fainting and carotid artery disease.

PMID- 22611835
TI  - Health care and cultural needs of client populations.

PMID- 22611836
TI  - Diabetes symptoms, health literacy, and health care use in adult Latinos with
      diabetes risk factors.
AB  - PURPOSE: This study examined the extent of undetected and untreated type 2
      diabetes in a sample of recent Latino immigrants, and looked at the relationships
      among diabetes symptoms, blood glucose level, diabetes knowledge, health literacy
      level, and health care use. METHODS: Using a descriptive and correlational
      design, 144 Latino adults were interviewed. RESULTS: Many participants had
      diabetes and reported symptoms, but they were not aware of the disease and were
      not receiving adequate health care. Lack of diabetes knowledge, low health
      literacy, and barriers to health care prevented appropriate symptom responses.
      CONCLUSIONS: Interventions that teach health literacy skills and diabetes symptom
      interpretation may improve health care use.

PMID- 22611837
TI  - An innovative approach to diabetes education for a Hispanic population utilizing
      community health workers.
AB  - Type 2 diabetes disproportionately affects the Hispanic population. New
      approaches are needed to provide effective education to this population. This
      evidence-based project utilized community health workers (CHWs) to deliver a
      culturally relevant diabetes education program to a Hispanic population at a
      migrant clinic. The program emphasized culturally relevant interventions to
      improve self-efficacy. Formative evaluation was used to develop and improve the
      program. Participants showed improvement in diabetes knowledge and diabetes
      related self-efficacy scores. Outcomes also included improvement in CHWs'
      diabetes knowledge and development of an educational program that could be
      utilized in other settings serving Hispanic populations with type 2 diabetes.

PMID- 22611838
TI  - Relationship between diabetes self-management education and self-care behaviors
      among African American women with type 2 diabetes.
AB  - The purpose of this study was to explore the extent to which African American
      women participate in diabetes self-management education (DSME) and the impact of
      participation on self-care behaviors. Results from the Behavioral Risk Factor
      Surveillance Survey (2007) revealed, approximately, 53.6% of participants
      reported having had DSME, less than the 62.5% participation rate suggested by
      Healthy People 2020. Those who received DSME were significantly more likely to
      check their own blood sugar and feet regularly; to participate in moderate
      physical activity; and to have received healthcare provider foot examinations,
      glycosolated hemoglobin measurements, and dilated eye examinations in the past
      year. These results indicate the importance of DSME and the need for health care
      providers to develop strategies and policies to improve participation among this
      ethnic group of women. Thereby, decreasing complications related to Type 2
      diabetes and improving the quality of life for these Women.

PMID- 22611839
TI  - Exploring the world outside to increase cultural competence of the educator
      within.
AB  - As nursing educators strive to increase cultural competence among students, it is
      important to consider professional development in the process. There are
      resources available to faculty in the form of small grants, and conference
      attendance/presentation monies. The author shares experiences related to travel
      to the 6th National Nursing Congress "with International participation" to
      Cappadocia Turkey. Discussion will include practical aspects of securing monies
      for travel opportunities, and post journey reflections that have been integrated
      into improving teaching of cultural content.

PMID- 22611840
TI  - English-as-a-Second Language (ESL) nursing student success: a critical review of
      the literature.
AB  - Many English-as-a-Second Language (ESL) nursing students struggle in nursing
      school for a multitude of reasons. The purpose of this critical review of the
      literature is to identify barriers and discover bridges to ESL nursing student
      success. Twenty-five articles were identified for the review. Language barriers
      were identified as the single most significant obstacle facing the ESL nursing
      student. Bridges to ESL nursing student success include enhancing language
      development and acculturation into the American mainstream culture. A broad range
      of strategies to promote student success are outlined and the role of the nurse
      educator in ESL nursing student success is also addressed.

PMID- 22611841
TI  - Evaluating the performance of methods for estimating the abundance of rapidly
      declining coastal shark populations.
AB  - Accurately surveying shark populations is critical to monitoring precipitous
      ongoing declines in shark abundance and interpreting the effects that these
      reductions are having on ecosystems. To evaluate the effectiveness of existing
      survey tools, we used field trials and computer simulations to critically examine
      the operation of four common methods for counting coastal sharks: stationary
      point counts, belt transects, video surveys, and mark and recapture abundance
      estimators. Empirical and theoretical results suggest that (1) survey method
      selection has a strong impact on the estimates of shark density that are
      produced, (2) standardizations by survey duration are needed to properly
      interpret and compare survey outputs, (3) increasing survey size does not
      necessarily increase survey precision, and (4) methods that yield the highest
      density estimates are not always the most accurate. These findings challenge some
      of the assumptions traditionally associated with surveying mobile marine animals.
      Of the methods we trialed, 8 x 50 m belt transects and a 20 m radius point count
      produced the most accurate estimates of shark density. These findings can help to
      improve the ways we monitor, manage, and understand the ecology of globally
      imperiled coastal shark populations.

PMID- 22611842
TI  - Global assessment of the non-equilibrium concept in rangelands.
AB  - The non-equilibrium concept of rangeland dynamics predicts that the potential for
      grazing-induced degradation is low in rangelands with relatively variable
      precipitation. To date, evidence in support of the non-equilibrium concept has
      been inconsistent. Using a standardized protocol, including a newly developed
      global map of rainfall variability, we reviewed the incidence of degradation in
      relation to rainfall variability across 58 published studies. We distinguished
      between (1) zonal degradation (i.e., degradation independent of water and key
      resources), (2) degradation in the presence of key resources, and (3) degradation
      in the presence of water. For studies not affected by proximity to permanent
      water or key resources, we found strong support for the non-equilibrium concept
      for rangelands. Zonal degradation was absent at CV (coefficient of variation)
      values above 33%, which has been proposed as a critical threshold. Grazing
      degradation was almost entirely restricted to areas with relatively stable annual
      precipitation as expressed by a low CV, or to rangelands with key resources or
      water points nearby. To better understand rangeland dynamics, we recommend that
      future studies use globally comparable measures of degradation and rainfall
      variability. Our work underlines that rangelands with relatively stable rainfall
      patterns, and those with access to water or key resources, are potentially
      vulnerable to degradation. Grazing management in such areas should incorporate
      strategic rest periods. Such rest periods effectively mimic natural fluctuations
      in herbivore populations, which are a defining characteristic of non-degraded
      rangelands occurring under highly variable precipitation regimes.

PMID- 22611843
TI  - Empirical assessment of state-and-transition models with a long-term vegetation
      record from the Sonoran Desert.
AB  - Resilience-based frameworks, including state-and-transition models (STM), are
      being increasingly called upon to inform policy and guide ecosystem management,
      particularly in rangelands. Yet, multiple challenges impede their effective
      implementation: (1) paucity of empirical tests of resilience concepts, such as
      alternative states and thresholds, and (2) heavy reliance on expert models, which
      are seldom tested against empirical data. We developed an analytical protocol to
      identify unique plant communities and their transitions, and applied it to a long
      term vegetation record from the Sonoran Desert (1953-2009). We assessed whether
      empirical trends were consistent with resilience concepts, and evaluated how they
      may inform the construction and interpretation of expert STMs. Seven
      statistically distinct plant communities were identified based on the cover of 22
      plant species in 68 permanent transects. We recorded 253 instances of community
      transitions, associated with changes in species composition between successive
      samplings. Expectedly, transitions were more frequent among proximate communities
      with similar species pools than among distant communities. But unexpectedly,
      communities and transitions were not strongly constrained by soil type and
      topography. Only 18 transitions featured disproportionately large compositional
      turnover (species dissimilarity ranged between 0.54 and 0.68), and these were
      closely associated with communities that were dominated by the common shrub
      (burroweed, Haplopappus tenuisecta); indicating that only some, and not all,
      communities may be prone to large compositional change. Temporal dynamics in
      individual transects illustrated four general trajectories: stability,
      nondirectional drift, reversibility, and directional shifts that were not
      reversed even after 2-3 decades. The frequency of transitions and the
      accompanying species dissimilarity were both positively correlated with
      fluctuation in precipitation, indicating that climatic drivers require more
      attention in STMs. Many features of the expert models, including the number of
      communities and participant species, were consistent with empirical trends, but
      expert models underrepresented recent increases in cacti while overemphasizing
      the introduced Lehmann's lovegrass (Eragrostis lehmanniana). Quantification of
      communities and transitions within long-term vegetation records presents several
      quantitative metrics such as transition frequency, magnitude of accompanying
      compositional change, presence of unidirectional trajectories, and lack of
      reversibility within various timescales, which can clarify resilience concepts
      and inform the construction and interpretation of STMs.

PMID- 22611844
TI  - The impact of the invasive shrub Lonicera maackii on the decomposition dynamics
      of a native plant community.
AB  - Invasive plants may have variable effects within a given environment depending on
      their interactions with the dominant native species, yet little research has
      examined such species-species interactions within a site. Savanna trees with
      nonoverlapping canopies offer an ideal opportunity to assess associated changes
      in the ecosystem processes that result from interactions between an invasive
      species and different native tree species. We examined the influence of the
      exotic invasive shrub Lonicera maackii on decomposition dynamics under three
      native tree species: Fraxinus quadrangulata, Quercus muehlenbergii, and Carya
      ovata. Litter decomposition rates and litter C and N were evaluated over two
      years using single- and mixed-species litterbags (L. maackii and individual tree
      species litter); microarthropod abundance was measured at 6 weeks using Tulgren
      funnels. Litter from the invasive L. maackii decomposed and lost N more rapidly
      than the litter of the three native tree species. The rate at which L. maackii
      decomposed depended on its location, with L. maackii litter decomposing and
      losing N more rapidly under C. ovata than under the other two native tree
      species. Mixing L. maackii with the native species' litter did not accelerate
      litter mass loss overall but did result in synergistic N losses at variable times
      throughout the experiment, further highlighting the variable interaction between
      native species and L. maackii. Nitrogen loss was significantly higher than
      expected in mixtures of C. ovata + L. maackii litter at 6 weeks, in F.
      quadrangulata + L. maackii litter at 12 weeks, and in Q. muehlenbergii + L.
      maackii litter at 24 weeks. If the effects of invasive species on certain
      ecosystem processes, such as litter decomposition, are strongly influenced by
      their association with native species, this could suggest the need for a more
      nuanced understanding of the vulnerability of ecosystem processes to invasions of
      L. maackii and potentially other invasive species.

PMID- 22611845
TI  - Grassland restoration with and without fire: evidence from a tree-removal
      experiment.
AB  - Forest encroachment threatens the biological diversity of grasslands globally.
      Positive feedbacks can reinforce the process, affecting soils and ground
      vegetation, ultimately leading to replacement of grassland by forest species. We
      tested whether restoration treatments (tree removal, with or without fire)
      reversed effects of nearly two centuries of encroachment by Abies grandis and
      Pinus contorta into dry, montane meadows in the Cascade Range, Oregon, USA. In
      nine, 1-ha plots containing a patchy mosaic of meadow openings and forests of
      varying age (20 to > 140 yr), we compared three treatments affecting the ground
      vegetation: control (no trees removed), unburned (trees removed, slash burned in
      piles leaving 90% of the area unburned), and burned (trees removed, slash
      broadcast burned). We quantified changes over 3-4 years in soils, abundance and
      richness of species with differing habitat associations (meadow, forest, and
      ruderal), and recruitment of conifers. Except for a transient increase in
      available N (especially in burn scars), effects of burning on soils were minimal
      due, in part, to mixing by gophers. Tree removal greatly benefited meadow species
      at the expense of forest herbs. Cover and richness of meadow species increased by
      47% and 38% of initial values in unburned plots, but changed minimally in burned
      plots. In contrast, cover and richness of forest herbs declined by 44% and 26% in
      unburned plots and by 79% and 58% in burned plots. Ruderal species and conifer
      seedlings were uncommon in both treatments. Although vegetation was consumed
      beneath burn piles, meadow species recovered significantly after three years.
      Long-term tree presence did not preclude recovery of meadow species; in fact,
      colonization was greater in older than in younger forests. In sum, temporal
      trends were positive for most indicators, suggesting strong potential for
      restoration. Contrary to conventional wisdom, tree removal without fire may be
      sufficient to shift the balance from forest to meadow species. In meadows
      characterized by historically infrequent fire, small-scale disturbances and
      competitive interactions may be more critical to ecosystem maintenance and
      restoration. Managers facing the worldwide phenomenon of tree invasion should
      critically evaluate the ecological vs. operational need for fire in ecosystem
      restoration.

PMID- 22611846
TI  - Do natural disturbances or the forestry practices that follow them convert
      forests to early-successional communities?
AB  - Stand-replacing natural disturbances in mature forests are traditionally seen as
      events that cause forests to revert to early stages of succession and maintain
      species diversity. In some cases, however, such transitions could be an artifact
      of salvage logging and may increase biotic homogenization. We present initial
      (two-year) results of a study of the effects of tornado damage and the combined
      effects of tornado damage and salvage logging on environmental conditions and
      ground cover plant communities in mixed oak-pine forests in north central
      Mississippi. Plots were established in salvage-logged areas, adjacent to plots
      established before the storm in unlogged areas, spanning a gradient of storm
      damage intensity. Vegetation change directly attributable to tornado damage was
      driven primarily by a reduction in canopy cover but was not consistent with a
      transition to an early stage of succession. Although we observed post-storm
      increases of several disturbance indicators (ruderals), we also observed
      significant increases in the abundance of a few species indicative of upland
      forests. Increases in flowering were just as likely to occur in species
      indicative of forests as in species indicative of open woodlands. Few species
      declined as a result of the tornado, resulting in a net increase in species
      richness. Ruderals were very abundant in salvage-logged areas, which contained
      significantly higher amounts of bare ground and greater variance in soil
      penetrability than did damaged areas that were not logged. In contrast to
      unlogged areas severely damaged by the tornado, most upland forest indicators
      were not abundant in logged areas. Several of the forest and open-woodland
      indicators that showed increased flowering in damaged areas were absent or sparse
      in logged areas. Species richness was lower in salvage-logged areas than in
      adjacent damaged areas but similar to that in undamaged areas. These results
      suggest that salvage logging prevented positive responses of several forest and
      open-woodland species to tornado damage. Anthropogenic disturbances such as
      salvage logging appear to differ fundamentally from stand-level canopy-reducing
      disturbances in their effects on ground cover vegetation in the forests studied
      here and are perhaps more appropriately viewed as contributing to biotic
      homogenization than as events that maintain diversity.

PMID- 22611847
TI  - A comparison of land-sharing and land-sparing strategies for plant richness
      conservation in agricultural landscapes.
AB  - Strategies for conserving plant diversity in agroecosystems generally focus on
      either expanding land area in non-crop habitat or enhancing diversity within crop
      fields through changes in within-field management practices. In this study, we
      compare effects on landscape-scale species richness from such land-sharing or
      land-sparing strategies. We collected data in arable field, grassland, pasture,
      and forest habitat types (1.6 ha sampled per habitat type) across a 100-km2
      region of farmland in Lancaster County, Pennsylvania, USA. We fitted species-area
      relationships (SARs) for each habitat type and then combined extrapolations from
      the curves with estimates of community overlap to estimate richness in a 314.5-ha
      landscape. We then modified these baseline estimates by adjusting parameters in
      the SAR models to compare potential effects of land-sharing and land-sparing
      conservation practices on landscape richness. We found that species richness of
      the habitat types showed a strong inverse relationship to the relative land area
      of each type in the region, with 89 species in arable fields (66.5% of total land
      area), 153 in pastures (6.7%), 196 in forests (5.2%), and 213 in grasslands
      (2.9%). Relative to the baseline scenario, major changes in the richness of
      arable fields produced gains in landscape-scale richness comparable to a
      conversion of 3.1% of arable field area into grassland habitat. Sensitivity
      analysis of our model indicated that relative gains from land sparing would be
      greatest in landscapes with a low amount of non-crop habitat in the baseline
      scenario, but that in more complex landscapes land sharing would provide greater
      gains. These results indicate that the majority of plant species in
      agroecosystems are found in small fragments of non-crop habitat and suggest that,
      especially in landscapes with little non-crop habitat, richness can be more
      readily conserved through land-sparing approaches.

PMID- 22611848
TI  - Modeling range dynamics in heterogeneous landscapes: invasion of the hemlock
      woolly adelgid in eastern North America.
AB  - Range expansion by native and exotic species will continue to be a major
      component of global change. Anticipating the potential effects of changes in
      species distributions requires models capable of forecasting population spread
      across realistic, heterogeneous landscapes and subject to spatiotemporal
      variability in habitat suitability. Several decades of theory and model
      development, as well as increased computing power and availability of fine
      resolution GIS data, now make such models possible. Still unanswered, however, is
      the question of how well this new generation of dynamic models will anticipate
      range expansion. Here we develop a spatially explicit stochastic model that
      combines dynamic dispersal and population processes with fine-resolution maps
      characterizing spatiotemporal heterogeneity in climate and habitat to model range
      expansion of the hemlock woolly adelgid (HWA; Adelges tsugae). We parameterize
      this model using multiyear data sets describing population and dispersal dynamics
      of HWA and apply it to eastern North America over a 57-year period (1951-2008).
      To evaluate the model, the observed pattern of spread of HWA during this same
      period was compared to model predictions. Our model predicts considerable
      heterogeneity in the risk of HWA invasion across space and through time, and it
      suggests that spatiotemporal variation in winter temperature, rather than hemlock
      abundance, exerts a primary control on the spread of HWA. Although the
      simulations generally matched the observed current extent of the invasion of HWA
      and patterns of anisotropic spread, it did not correctly predict when HWA was
      observed to arrive in different geographic regions. We attribute differences
      between the modeled and observed dynamics to an inability to capture the timing
      and direction of long-distance dispersal events that substantially affected the
      ensuing pattern of spread.

PMID- 22611849
TI  - Development and application of multi-proxy indices of land use change for
      riparian soils in southern New England, USA.
AB  - Understanding the effects of land use on riparian systems is dependent upon the
      development of methodologies to recognize changes in sedimentation related to
      shifts in land use. Land use trends in southern New England consist of shifts
      from forested precolonial conditions, to colonial and agrarian land uses, and
      toward modern industrial-urban landscapes. The goals of this study were to
      develop a set of stratigraphic indices that reflect these land use periods and to
      illustrate their applications. Twenty-four riparian sites from first- and second
      order watersheds were chosen for study. Soil morphological features, such as
      buried surface horizons (layers), were useful to identify periods of watershed
      instability. The presence of human artifacts and increases in heavy metal
      concentration above background levels, were also effective indicators of
      industrial-urban land use periods. Increases and peak abundance of non-arboreal
      weed pollen (Ambrosia) were identified as stratigraphic markers indicative of
      agricultural land uses. Twelve 14C dates from riparian soils indicated that the
      rise in non-arboreal pollen corresponds to the start of regional deforestation
      (AD 1749 +/- 56 cal yr; mean +/- 2 SD) and peak non-arboreal pollen concentration
      corresponds to maximum agricultural land use (AD 1820 +/- 51 cal yr). These
      indices were applied to elucidate the impact of land use on riparian
      sedimentation and soil carbon (C) dynamics. This analysis indicated that the
      majority of sediment and soil organic carbon (SOC) stored in regional riparian
      soils is of postcolonial origins. Mean net sedimentation rates increased -100
      fold during postcolonial time periods, and net SOC sequestration rates showed an
      approximate 200-fold increase since precolonial times. These results suggest that
      headwater riparian zones have acted as an effective sink for alluvial sediment
      and SOC associated with postcolonial land use.

PMID- 22611850
TI  - Compositional stability and diversity of vascular plant communities following
      logging disturbance in Appalachian forests.
AB  - Human-caused changes in disturbance regimes and introductions of nonnative
      species have the potential to result in widespread, directional changes in forest
      community structure. The degree that plant community composition persists or
      changes following disturbances depends on the balance between local extirpation
      and colonization by new species, including nonnatives. In this study, we examined
      species losses and gains, and entry of native vs. exotic species to determine how
      oak forests in the Appalachian Mountains might shift in species composition
      following a gradient of pulse disturbances (timber harvesting). We asked (1) how
      compositional stability of the plant community (resistance and resilience) was
      influenced by disturbance intensity, (2) whether community responses were driven
      by extirpation or colonization of species, and (3) how disturbance intensity
      influenced total and functional group diversity, including the nonnative
      proportion of the flora through time. We collected data at three spatial scales
      and three times, including just before, one year post-disturbance, and 10 years
      post-disturbance. Resistance was estimated using community distance measures
      between pre- and one year post-disturbance, and resilience using community
      distance between pre- and 10-year post-disturbance conditions. The number of
      colonizing and extirpated species between sampling times was analyzed for all
      species combined and for six functional groups. Resistance and resilience
      decreased with increasing timber-harvesting disturbance; compositional stability
      was lower in the most disturbed plots, which was driven by colonization, but not
      extirpation, of species. Colonization of species also led to increases in
      diversity after disturbance that was typically maintained after 10 years
      following disturbance. Most of the community-level responses were driven by post
      disturbance colonization of native forbs and graminoids. The nonnative proportion
      of plant species tended to increase following disturbance, especially at large
      spatial scales in the most disturbed treatments, but tended to decrease through
      time following disturbance due to canopy development. The results of this study
      are consistent with the theory that resources released by disturbance have strong
      influences on species colonization and community composition. The effects of
      management activities tested in this study, which span a gradient of timber
      harvesting disturbance, shift species composition largely via an increase in
      species colonization and diversity.

PMID- 22611851
TI  - Trends over time in tree and seedling phylogenetic diversity indicate regional
      differences in forest biodiversity change.
AB  - Changing climate conditions may impact the short-term ability of forest tree
      species to regenerate in many locations. In the longer term, tree species may be
      unable to persist in some locations while they become established in new places.
      Over both time frames, forest tree biodiversity may change in unexpected ways.
      Using repeated inventory measurements five years apart from more than 7000
      forested plots in the eastern United States, we tested three hypotheses:
      phylogenetic diversity is substantially different from species richness as a
      measure of biodiversity; forest communities have undergone recent changes in
      phylogenetic diversity that differ by size class, region, and seed dispersal
      strategy; and these patterns are consistent with expected early effects of
      climate change. Specifically, the magnitude of diversity change across broad
      regions should be greater among seedlings than in trees, should be associated
      with latitude and elevation, and should be greater among species with high
      dispersal capacity. Our analyses demonstrated that phylogenetic diversity and
      species richness are decoupled at small and medium scales and are imperfectly
      associated at large scales. This suggests that it is appropriate to apply
      indicators of biodiversity change based on phylogenetic diversity, which account
      for evolutionary relationships among species and may better represent community
      functional diversity. Our results also detected broadscale patterns of forest
      biodiversity change that are consistent with expected early effects of climate
      change. First, the statistically significant increase over time in seedling
      diversity in the South suggests that conditions there have become more favorable
      for the reproduction and dispersal of a wider variety of species, whereas the
      significant decrease in northern seedling diversity indicates that northern
      conditions have become less favorable. Second, we found weak correlations between
      seedling diversity change and latitude in both zones, with stronger relationships
      apparent in some ecoregions. Finally, we detected broadscale seedling diversity
      increases among species with longer-distance dispersal capacity, even in the
      northern zone, where overall seedling diversity declined. The statistical power
      and geographic extent of such analyses will increase as data become available
      over larger areas and as plot measurements are repeated at regular intervals over
      a longer period of time.

PMID- 22611852
TI  - Disrupting mycorrhizal mutualisms: a potential mechanism by which exotic tamarisk
      outcompetes native cottonwoods.
AB  - The disruption of mutualisms between plants and mycorrhizal fungi is a
      potentially powerful mechanism by which invasives can negatively impact native
      species, yet our understanding of this mechanism's role in exotic species
      invasion is still in its infancy. Here, we provide several lines of evidence
      indicating that invasive tamarisk (Tamarix sp.) negatively affects native
      cottonwoods (Populus fremontii) by disrupting their associations with arbuscular
      mycorrhizal (AM) and ectomycorrhizal (EM) fungi. At a field site in the early
      stages of tamarisk invasion, cottonwoods with tamarisk neighbors had reduced EM
      colonization and altered EM fungal community composition relative to cottonwoods
      with native neighbors, leading to reductions in EM propagule abundance in the
      soil beneath tamarisk. Similarly, AM colonization of cottonwoods was reduced with
      a tamarisk neighbor, but there were no significant changes in AM fungal spore
      communities or propagule abundance. Root colonization by nonmycorrhizal fungi,
      including potential pathogens, was higher in cottonwoods with tamarisk neighbors.
      A greenhouse experiment in which AM and EM inoculation and plant neighbor were
      manipulated in a fully factorial design showed that cottonwoods benefited from
      mycorrhizas, especially EM, in terms of shoot biomass when grown with a
      conspecific, but shoot biomass was similar to that of nonmycorrhizal controls
      when cottonwoods were grown with a tamarisk neighbor. These results are partially
      explained by a reduction in EM but not AM colonization of cottonwoods by a
      tamarisk neighbor. Tamarisk neighbors negatively affected cottonwood specific
      leaf area, but not chlorophyll content, in the field. To pinpoint a mechanism for
      these changes, we measured soil chemistry in the field and the growth response of
      an EM fungus (Hebeloma crustuliniforme) to salt-amended media in the laboratory.
      Tamarisk increased both NO3- concentrations and electrical conductivity 2.5-fold
      beneath neighboring cottonwoods in the field. Salt-amended media did not affect
      the growth of H. crustuliniforme. Our findings demonstrate that a nonnative
      species, even in the early stages of invasion, can negatively affect a native
      species by disrupting its mycorrhizal symbioses. Some of these changes in
      mycorrhizal fungal communities may remain as legacy effects of invasives, even
      after their removal, and should be considered in management and restoration
      efforts.

PMID- 22611853
TI  - Divergence in ectomycorrhizal communities with foreign Douglas-fir populations
      and implications for assisted migration.
AB  - Assisted migration of forest trees has been widely proposed as a climate change
      adaptation strategy, but moving tree populations to match anticipated future
      climates may disrupt the geographically based, coevolved association suggested to
      exist between host trees and ectomycorrhizal fungal (EMF) communities. We
      explored this issue by examining the consistency of EMF communities among
      populations of 40 year-old Douglas-fir (Pseudotsuga menziesii var. menziesii)
      trees in a common-garden field trial using four provenances from contrasting
      coastal climates in southwestern British Columbia. Considerable variation in EMF
      community composition within test sites was found, ranging from 0.38 to 0.65 in
      the mean similarity index, and the divergence in EMF communities from local
      populations increased with site productivity. Clinal patterns in colonization
      success were detected for generalist and specialist EMF species on only the two
      productive test sites. Host population effects were limited to EMF species
      abundance rather than species loss, as richness per site averaged 15.0 among
      provenances and did not differ by transfer extent (up to 450 km), while Shannon's
      diversity index declined slightly. Large differences in colonization rates of
      specialist fungi, such as Tomentella stuposa and Clavulina cristata, raise the
      possibility that EMF communities maladapted to soil conditions contributed to the
      inferior growth of some host populations on productive sites. The results of the
      study suggest locally based specificity in host-fungal communities is likely a
      contributing factor in the outcome of provenance trials, and should be a
      consideration in analyzing seed-transfer effects and developing strategies for
      assisted migration.

PMID- 22611854
TI  - Reduced-impact logging and biodiversity conservation: a case study from Borneo.
AB  - A key driver of rain forest degradation is rampant commercial logging. Reduced
      impact logging (RIL) techniques dramatically reduce residual damage to vegetation
      and soils, and they enhance the long-term economic viability of timber operations
      when compared to conventionally managed logging enterprises. Consequently, the
      application of RIL is increasing across the tropics, yet our knowledge of the
      potential for RIL also to reduce the negative impacts of logging on biodiversity
      is minimal. We compare the impacts of RIL on birds, leaf-litter ants, and dung
      beetles during a second logging rotation in Sabah, Borneo, with the impacts of
      conventional logging (CL) as well as with primary (unlogged) forest. Our study
      took place 1-8 years after the cessation of logging. The species richness and
      composition of RIL vs. CL forests were very similar for each taxonomic group.
      Both RIL and CL differed significantly from unlogged forests in terms of bird and
      ant species composition (although both retained a large number of the species
      found in unlogged forests), whereas the composition of dung beetle communities
      did not differ significantly among forest types. Our results show little
      difference in biodiversity between RIL and CL over the short-term. However,
      biodiversity benefits from RIL may accrue over longer time periods after the
      cessation of logging. We highlight a severe lack of studies investigating this
      possibility. Moreover, if RIL increases the economic value of selectively logged
      forests (e.g., via REDD+, a United Nations program: Reducing Emissions from
      Deforestation and Forest Degradation in Developing Countries), it could help
      prevent them from being converted to agricultural plantations, which results in a
      tremendous loss of biodiversity.

PMID- 22611855
TI  - A universal approach to estimate biomass and carbon stock in tropical forests
      using generic allometric models.
AB  - Allometric equations allow aboveground tree biomass and carbon stock to be
      estimated from tree size. The allometric scaling theory suggests the existence of
      a universal power-law relationship between tree biomass and tree diameter with a
      fixed scaling exponent close to 8/3. In addition, generic empirical models, like
      Chave's or Brown's models, have been proposed for tropical forests in America and
      Asia. These generic models have been used to estimate forest biomass and carbon
      worldwide. However, tree allometry depends on environmental and genetic factors
      that vary from region to region. Consequently, theoretical models that include
      too few ecological explicative variables or empirical generic models that have
      been calibrated at particular sites are unlikely to yield accurate tree biomass
      estimates at other sites. In this study, we based our analysis on a destructive
      sample of 481 trees in Madagascar spiny dry and moist forests characterized by a
      high rate of endemism (> 95%). We show that, among the available generic
      allometric models, Chave's model including diameter, height, and wood specific
      gravity as explicative variables for a particular forest type (dry, moist, or wet
      tropical forest) was the only one that gave accurate tree biomass estimates for
      Madagascar (R2 > 83%, bias < 6%), with estimates comparable to those obtained
      with regional allometric models. When biomass allometric models are not available
      for a given forest site, this result shows that a simple height-diameter
      allometry is needed to accurately estimate biomass and carbon stock from plot
      inventories.

PMID- 22611856
TI  - Landscape context and scale differentially impact coffee leaf rust, coffee berry
      borer, and coffee root-knot nematodes.
AB  - Crop pest and disease incidences at plot scale vary as a result of landscape
      effects. Two main effects can be distinguished. First, landscape context provides
      habitats of variable quality for pests, pathogens, and beneficial and vector
      organisms. Second, the movements of these organisms are dependent on the
      connectivity status of the landscape. Most of the studies focus on indirect
      effects of landscape context on pest abundance through their predators and
      parasitoids, and only a few on direct effects on pests and pathogens. Here we
      studied three coffee pests and pathogens, with limited or no pressure from host
      specific natural enemies, and with widely varying life histories, to test their
      relationships with landscape context: a fungus, Hemileia vastatrix, causal agent
      of coffee leaf rust; an insect, the coffee berry borer, Hypothenemus hampei
      (Coleoptera: Curculionidae); and root-knot nematodes, Meloidogyne spp. Their
      incidence was assessed in 29 coffee plots from Turrialba, Costa Rica. In
      addition, we characterized the landscape context around these coffee plots in 12
      nested circular sectors ranging from 50 to 1500 m in radius. We then performed
      correlation analysis between proportions of different land uses at different
      scales and coffee pest and disease incidences. We obtained significant positive
      correlations, peaking at the 150 m radius, between coffee berry borer abundance
      and proportion of coffee in the landscape. We also found significant positive
      correlations between coffee leaf rust incidence and proportion of pasture,
      peaking at the 200 m radius. Even after accounting for plot level predictors of
      coffee leaf rust and coffee berry borer through covariance analysis, the
      significance of landscape structure was maintained. We hypothesized that
      connected coffee plots favored coffee berry borer movements and improved its
      survival. We also hypothesized that wind turbulence, produced by low-wind
      resistance land uses such as pasture, favored removal of coffee leaf rust spore
      clusters from host surfaces, resulting in increased epidemics. In contrast, root
      knot nematode population density was not correlated to landscape context,
      possibly because nematodes are almost immobile in the soil. We propose
      fragmenting coffee plots with forest corridors to control coffee berry borer
      movements between coffee plots without favoring coffee leaf rust dispersal.

PMID- 22611857
TI  - Implementation of a marine reserve has a rapid but short-lived effect on
      recreational angler use.
AB  - Changes in human behavior are a precursor to measurable impacts of no-take marine
      reserves. We investigated changes in recreational fishing site selection in
      response to the 2005 announcement of enforcement in a marine reserve in the Gulf
      of California, Mexico. We used a novel data set of daily self-reported boating
      destinations from emergency rescue logbooks for a recreational angling community
      from 2000 to 2008. Because the reserve system has no experimental control, we
      modeled the data two ways to test for robustness to model specification. We
      tested for changes in human fishing behavior with regression and fit a fleet
      level discrete choice model to project a. counterfactual scenario. The
      counterfactual is the statistically constructed ex post expectation of the human
      behavior we would have observed if the reserve never existed. We included month
      and year fixed effects in our models to account for seasonal and interannual
      fluctuations in fishing behavior and catch rates. We detected a decrease in
      reserve use compared to the counterfactual, indicating that the reserve rapidly
      experienced a decrease in visitation. However, the reserve's effect to reduce
      trips diminished with time. These results indicate that the reserve is unlikely
      to meet its ecological goals without institutional changes that enhance
      compliance. This illustrates the value of human use data to understanding the
      processes underlying marine reserve function. We suggest that managers should
      consider human use with the same frequency, rigor, and tools as they do fishery
      stocks. Marine reserves directly affect people, and understanding human
      behavioral responses to marine reserves is an important step in marine reserve
      management.

PMID- 22611858
TI  - Mercury bioaccumulation in estuarine food webs.
AB  - We tested for unintended mercury contamination problems associated with estuarine
      floodplain restoration projects of the Louisiana coastal zone, USA. Barataria Bay
      and Breton Sound are two neighboring deltaic estuaries that were isolated by
      levees from the Mississippi River about 100 years ago. These estuaries recently
      have been reconnected to the nutrient-rich Mississippi River, starting major
      river diversion (input) flows in 1991 for Breton Sound and in 2004 for Barataria
      Bay. We collected > 2100 fish over five years from 20 stations in these estuaries
      to test two hypotheses about Hg bioaccumulation: (H1) Background Hg
      bioaccumulation in fish would be highest in low-salinity upper reaches of
      estuaries, and (H2) recent river inputs to these upper estuarine areas would
      increase Hg bioaccumulation in fish food webs. For H1, we surveyed fish Hg
      concentrations at several stations along a salinity gradient in Barataria Bay in
      2003-2004, a time when this estuary lacked strong river inputs. Results showed
      that average Hg concentrations in fish communities were lowest (150 ng/g dry
      mass) in higher salinity areas and -2.4x higher (350 ng/g) in low-salinity
      oligohaline and freshwater upper reaches of the estuary. For H2, we tested for
      enhanced Hg bioaccumulation following diversion onset in both estuaries. Fish
      communities from Breton Sound that had long-term (> 10 years) diversion inputs
      had -1.7x higher average Hg contents of 610 ng/g Hg vs. 350 ng/g background
      values. Shorter-term diversion inputs over 2-3 years in upper Barataria Bay did
      not result in strong Hg enrichments or stable C isotope increases seen in Breton
      Sound, even though N and S stable-isotope values indicated strong river inputs in
      both estuaries. It may be that epiphyte communities on abundant submerged aquatic
      vegetation (SAV) are important hotspots for Hg cycling in these estuaries, and
      observed lesser development of these epiphyte communities in upper Barataria Bay
      during the first years of diversion inputs may account for the lessened Hg
      bioaccumulation in fish. A management consideration from this study is that river
      restoration projects may unintentionally fertilize SAV and epiphyte-based food
      webs, leading to higher Hg bioaccumulation in river-impacted floodplains and
      their food webs.

PMID- 22611859
TI  - Is catchment productivity a useful predictor of taxa richness in lake plankton
      communities?
AB  - The influence of catchment variables on lake organisms is understudied. The
      terrestrial zone in the vicinity of lakes is, however, probably highly important
      for biota due to the effects on water chemistry and to various processes
      operating across ecosystem boundaries. We examined the relative importance of
      lake and catchment variables, as well as large-scale geographical factors, on the
      taxa richness of phyto- and zooplankton in 100 small lakes in Finland. In
      variation partitioning, the variability of phytoplankton richness was most
      strongly related to the effects of lake variables, the joint effects of lake and
      catchment variables, and the joint effects of all three groups of variables.
      Zooplankton richness, in turn, was most strongly related to the effects of lake
      and catchment variables and the joint effect of lake and catchment variables. The
      exact results of the variation partitioning depended on the catchment sizes
      considered in the regression models. Among lake variables, planktonic richness
      was strongly related to variables indicating productivity. Among catchment
      variables, the normalized difference vegetation index (NDVI), indicating
      catchment productivity, showed a relatively strong association with planktonic
      richness. These results provide evidence that catchment variables such as the
      NDVI may be efficient predictors of planktonic richness in small lakes. It is
      possible that individual lakes embedded in a highly productive landscape have
      higher taxa richness than solitary, potentially productive lakes because of the
      high influx of dispersing propagules from the regional pool. We also suggest that
      catchment variables may respond to environmental changes at different scales than
      the lake variables, and explicit consideration of catchment productivity would
      therefore be useful when planning research and monitoring programs for freshwater
      organisms.

PMID- 22611860
TI  - New effects of Roundup on amphibians: predators reduce herbicide mortality;
      herbicides induce antipredator morphology.
AB  - The use of pesticides is important for growing crops and protecting human health
      by reducing the prevalence of targeted pest species. However, less attention is
      given to the potential unintended effects on nontarget species, including
      taxonomic groups that are of current conservation concern. One issue raised in
      recent years is the potential for pesticides to become more lethal in the
      presence of predatory cues, a phenomenon observed thus far only in the
      laboratory. A second issue is whether pesticides can induce unintended trait
      changes in nontarget species, particularly trait changes that might mimic
      adaptive responses to natural environmental stressors. Using outdoor mesocosms, I
      created simple wetland communities containing leaf litter, algae, zooplankton,
      and three species of tadpoles (wood frogs [Rana sylvatica or Lithobates
      sylvaticus], leopard frogs [R. pipiens or L. pipiens], and American toads [Bufo
      americanus or Anaxyrus americanus]). I exposed the communities to a factorial
      combination of environmentally relevant herbicide concentrations (0, 1, 2, or 3
      mg acid equivalents [a.e.]/L of Roundup Original MAX) crossed with three predator
      cue treatments (no predators, adult newts [Notophthalmus viridescens], or larval
      dragonflies [Anax junius]). Without predator cues, mortality rates from Roundup
      were consistent with past studies. Combined with cues from the most risky
      predator (i.e., dragonflies), Roundup became less lethal (in direct contrast to
      past laboratory studies). This reduction in mortality was likely caused by the
      herbicide stratifying in the water column and predator cues scaring the tadpoles
      down to the benthos where herbicide concentrations were lower. Even more striking
      was the discovery that Roundup induced morphological changes in the tadpoles. In
      wood frog and leopard frog tadpoles, Roundup induced relatively deeper tails in
      the same direction and of the same magnitude as the adaptive changes induced by
      dragonfly cues. To my knowledge, this is the first study to show that a pesticide
      can induce morphological changes in a vertebrate. Moreover, the data suggest that
      the herbicide might be activating the tadpoles' developmental pathways used for
      antipredator responses. Collectively, these discoveries suggest that the world's
      most widely applied herbicide may have much further-reaching effects on nontarget
      species than previous considered.

PMID- 22611861
TI  - Predator-prey spatial game as a tool to understand the effects of protected areas
      on harvester-wildlife interactions.
AB  - No-take reserves are sometimes implemented for sustainable population harvesting
      because they offer opportunities for animals to spatially avoid harvesters,
      whereas harvesters can benefit in return from the reserve spillover. Here, we
      used the framework of predator-prey spatial games to understand how protected
      areas shape spatial interactions between harvesters and target species and
      determine animal mortality. In these spatial games, the "predator" searches for
      "prey" and matches their habitat use, unless it meets spatial constraints
      offering the opportunity for prey to avoid the mortality source. However, such
      prey refuges could attract predators in the surroundings, which questions the
      potential benefits for prey. We located, in the Geneva Basin (France), hunting
      dogs and wild boar Sus scrofa L. during hunting seasons with global positioning
      systems and very-high-frequency collars. We quantified how the proximity of the
      reserve shaped the matching between both habitat uses using multivariate analyses
      and linked these patterns to animals' mortality with a Cox regression analysis.
      Results showed that habitat uses by both protagonists disassociated only when
      hunters were spatially constrained by the reserve. In response, hunters increased
      hunting efforts near the reserve boundary, which induced a higher risk exposure
      for animals settled over the reserve. The mortality of adult wild boar decreased
      near the reserve as the mismatch between both habitat uses increased. However the
      opposite pattern was determined for younger individuals that suffered from the
      high level of hunting close to the reserve. The predator-prey analogy was an
      accurate prediction of how the protected area modified spatial relationships
      between harvesters and target species. Prey-searching strategies adopted by
      hunters around reserves strongly impacted animal mortality and the efficiency of
      the protected area for this harvested species. Increasing reserve sizes and/or
      implementing buffer areas with harvesting limitations can dampen this edge effect
      and helps harvesters to benefit durably from source populations of reserves.
      Predator-prey spatial games therefore provide a powerful theoretical background
      for understanding wildlife-harvester spatial interactions and developing
      substantial application for sustainable harvesting.

PMID- 22611863
TI  - A Bayesian hierarchical model of Antarctic fur seal foraging and pup growth
      related to sea ice and prey abundance.
AB  - We created a Bayesian hierarchical model (BHM) to investigate ecosystem
      relationships between the physical ecosystem (sea ice extent), a prey measure
      (krill density), predator behaviors (diving and foraging effort of female
      Antarctic fur seals, Arctocephalus gazella, with pups) and predator
      characteristics (mass of maternal fur seals and pups). We collected data on
      Antarctic fur seals from 1987/1988 to 1994/1995 at Seal Island, Antarctica. The
      BHM allowed us to link together predators and prey into a model that uses all the
      data efficiently and accounts for major sources of uncertainty. Based on the
      literature, we made hypotheses about the relationships in the model, which we
      compared with the model outcome after fitting the BHM. For each BHM parameter, we
      calculated the mean of the posterior density and the 95% credible interval. Our
      model confirmed others' findings that increased sea ice was related to increased
      krill density. Higher krill density led to reduced dive intensity of maternal fur
      seals, as measured by dive depth and duration, and to less time spent foraging by
      maternal fur seals. Heavier maternal fur seals and lower maternal foraging effort
      resulted in heavier pups at 22 d. No relationship was found between krill density
      and maternal mass, or between maternal mass and foraging effort on pup growth
      rates between 22 and 85 days of age. Maternal mass may have reflected
      environmental conditions prior to the pup provisioning season, rather than summer
      prey densities. Maternal mass and foraging effort were not related to pup growth
      rates between 22 and 85 d, possibly indicating that food was not limiting, food
      sources other than krill were being used, or differences occurred before pups
      reached age 22 d.

PMID- 22611862
TI  - The effect of deer management on the abundance of Ixodes ricinus in Scotland.
AB  - The management of wildlife hosts for controlling parasites and disease has a
      history of mixed success. Deer can be important hosts for ticks, such as Ixodes
      ricinus, which is the primary vector of disease-causing zoonotic pathogens in
      Europe. Deer are generally managed by culling and fencing for forestry
      protection, habitat conservation, and commercial hunting, and in this study we
      test whether these deer management methods can be useful for controlling ticks,
      with implications for tick-borne pathogens. At different spatial scales and
      habitats we tested the hypotheses that tick abundance is reduced by (1) culling
      deer and (2) deer exclusion using fencing. We compared abundance indices of hosts
      and questing I. ricinus nymphs using a combination of small-scale fencing
      experiments on moorland, a large-scale natural experiment of fenced and unfenced
      pairs of forests, and cross-sectional surveys of forest and moorland areas with
      varying deer densities. As predicted, areas with fewer deer had fewer ticks, and
      fenced exclosures had dramatically fewer ticks in both large-scale forest and
      small-scale moorland plots. Fencing and reducing deer density were also
      associated with higher ground vegetation. The implications of these results on
      other hosts, pathogen prevalence, and disease risk are discussed. This study
      provides evidence of how traditional management methods of a keystone species can
      reduce a generalist parasite, with implications for disease risk mitigation.

PMID- 22611864
TI  - Effects of time since fire on birds: how informative are generalized fire
      response curves for conservation management?
AB  - Fire is both a widespread natural disturbance that affects the distribution of
      species and a tool that can be used to manage habitats for species. Knowledge of
      temporal changes in the occurrence of species after fire is essential for
      conservation management in fire-prone environments. Two key issues are: whether
      postfire responses of species are idiosyncratic or if multiple species show a
      limited number of similar responses; and whether such responses to time since
      fire can predict the occurrence of species across broad spatial scales. We
      examined the response of bird species to time since fire in semiarid shrubland in
      southeastern Australia using data from surveys at 499 sites representing a 100
      year chronosequence. We used nonlinear regression to model the probability of
      occurrence of 30 species with time since fire in two vegetation types, and
      compared species' responses with generalized response shapes from the literature.
      The occurrence of 16 species was significantly influenced by time since fire:
      they displayed six main responses consistent with generalized response shapes. Of
      these 16 species, 15 occurred more frequently in mid- or later-successional
      vegetation (> 20 years since fire), and only one species occurred more often in
      early succession (< 5 years since fire). The models had reasonable predictive
      ability for eight species, some predictive ability for seven species, and were
      little better than random for one species. Bird species displayed a limited range
      of responses to time since fire; thus a small set of fire ages should allow the
      provision of habitat for most species. Postfire successional changes extend for
      decades and management of the age class distribution of vegetation will need to
      reflect this timescale. Response curves revealed important seral stages for
      species and highlighted the importance of mid- to late-successional vegetation (>
      20 years). Although time since fire clearly influences the distribution of
      numerous bird species, predictive models of the spatial distribution of species
      in fire-prone landscapes need to incorporate other factors in addition to time
      since fire.

PMID- 22611865
TI  - Choosing ecosystem service investments that are robust to uncertainty across
      multiple parameters.
AB  - Info-gap decision theory facilitates decision making for problems in which
      uncertainty is large and probability distributions of uncertain variables are
      unknown. The info-gap framework allows the decision maker to maximize robustness
      to failure in the presence of uncertainty, where uncertainty is in the parameters
      of the model and failure is defined as the model output falling below some
      minimally acceptable performance threshold. Info-gap theory has found particular
      application to problems in conservation biology and ecological economics. In this
      study, we applied info-gap theory to an ecosystem services tradeoff case study in
      which a decision maker aiming to maximize ecosystem service investment returns
      must choose between two alternative land uses: native vegetation conservation or
      the establishment of an exotic timber plantation. The uncertain variables are the
      carbon price and the water price. With a "no-information" uncertainty model that
      assumes equal relative uncertainty across both variables, info-gap theory
      identifies a minimally acceptable reward threshold above which conservation is
      preferred, but below which plantation establishment is preferred. However, with
      an uncertainty model that allows the carbon price to be substantially more
      uncertain than the water price, conservation of native vegetation becomes an
      economically more robust investment option than establishing alien pine
      plantations. We explored the sensitivity of the results to the use of alternative
      uncertainty models, including asymmetric uncertainty in individual variables. We
      emphasize the general finding that the results of info-gap analyses can be
      sensitive to the choice of uncertainty model and that, therefore, future
      applications to ecological problems should be careful to incorporate all
      available qualitative and quantitative information relating to uncertainties or
      should at least justify the no-information uncertainty model.

PMID- 22611866
TI  - Phosphorus in Phoenix: a budget and spatial representation of phosphorus in an
      urban ecosystem.
AB  - As urban environments dominate the landscape, we need to examine how limiting
      nutrients such as phosphorus (P) cycle in these novel ecosystems. Sustainable
      management of P resources is necessary to ensure global food security and to
      minimize freshwater pollution. We used a spatially explicit budget to quantify
      the pools and fluxes of P in the Greater Phoenix Area in Arizona, USA, using the
      boundaries of the Central Arizona-Phoenix Long-Term Ecological Research site.
      Inputs were dominated by direct imports of food and fertilizer for local
      agriculture, while most outputs were small, including water, crops, and material
      destined for recycling. Internally, fluxes were dominated by transfers of food
      and feed from local agriculture and the recycling of human and animal excretion.
      Spatial correction of P dynamics across the city showed that human density and
      associated infrastructure, especially asphalt, dominated the distribution of P
      pools across the landscape. Phosphorus fluxes were dominated by agricultural
      production, with agricultural soils accumulating P. Human features
      (infrastructure, technology, and waste management decisions) and biophysical
      characteristics (soil properties, water fluxes, and storage) mediated P dynamics
      in Phoenix. P cycling was most notably affected by water management practices
      that conserve and recycle water, preventing the loss of waterborne P from the
      ecosystem. P is not intentionally managed, and as a result, changes in land use
      and demographics, particularly increased urbanization and declining agriculture,
      may lead to increased losses of P from this system. We suggest that city managers
      should minimize cross-boundary fluxes of P to the city. Reduced P fluxes may be
      accomplished through more efficient recycling of waste, therefore decreasing
      dependence on external nonrenewable P resources and minimizing aquatic pollution.
      Our spatial approach and consideration of both pools and fluxes across a
      heterogeneous urban ecosystem increases the utility of nutrient budgets for city
      managers. Our budget explicitly links processes that affect P cycling across
      space with the management of other resources (e.g., water). A holistic management
      strategy that deliberately couples the management of P and other resources should
      be a priority for cities in achieving urban sustainability.

PMID- 22611867
TI  - The width of riparian habitats for understory birds in an Amazonian forest.
AB  - Riparian habitats are important for the maintenance of regional biodiversity.
      Many studies have compared bird distributions between riparian and non-riparian
      habitats but have not established how wide riparian habitats used by birds are,
      as measured by distance from the nearest stream. We investigated the distribution
      of understory birds along gradients of distance from streams, soil clay content,
      and slope in a central Amazonian forest, by mist-netting birds three times in 45
      plots. We used nonmetric multidimensional scaling (NMDS) to reduce the
      dimensionality of species quantitative (abundance) and qualitative (presence
      absence) composition to one multivariate axis. Estimates of the width of riparian
      habitats as indicated by understory birds depended on the community attribute
      considered, measuring 90 m for species quantitative composition and 140 m for
      species qualitative composition. Species distributions were correlated with clay
      content but were independent of slope, while distance from streams was positively
      correlated with clay content but independent of slope. Clay content affects plant
      species composition, which in turn, may influence bird species composition.
      However, distribution patterns of birds in relation to distance from streams are
      consistent among studies carried out in many different temperate and tropical
      regions, indicating an effect of distance from streams itself. Protection of
      riparian habitats is one of the most widely used conservation strategies, and
      Brazilian environmental legislation mandates the protection of a 30 m wide strip
      of riparian vegetation on either side of small streams. We show that the
      protected strip should be much wider and recommend strategies to place other
      forms of land protection contiguous with riparian areas so that Brazilian
      environmental legislation better fulfills its role of protecting biodiversity
      associated with riparian habitats.

PMID- 22611868
TI  - Biomechanical assessment of surgical repair of the mitral valve.
AB  - Repair of the mitral valve is defined (loosely) as a procedure that alters the
      valve structure, without replacement, enabling the natural valve itself to
      continue to perform under the physical conditions to which it is exposed. As the
      mitral valve is driven by flow and pressure, it should be feasible to analyse and
      assess its function, failure and repair as a mechanical system. This article
      reviews the current state of mechanical evaluation of surgical repairs of the
      failed mitral valve of the heart. This review describes the anatomy and
      physiology of the mitral valve, followed by the failure of the mitral valve from
      a mechanical point of view. The surgical methods used to repair failed valves are
      introduced, while the use of engineering analysis to aid understanding of mitral
      valve repair is also reviewed. Finally, a section on recommendations for
      development and future uses of engineering techniques to surgical repair are
      presented.

PMID- 22611869
TI  - Fluid, solid and fluid-structure interaction simulations on patient-based
      abdominal aortic aneurysm models.
AB  - This article describes the use of fluid, solid and fluid-structure interaction
      simulations on three patient-based abdominal aortic aneurysm geometries. All
      simulations were carried out using OpenFOAM, which uses the finite volume method
      to solve both fluid and solid equations. Initially a fluid-only simulation was
      carried out on a single patient-based geometry and results from this simulation
      were compared with experimental results. There was good qualitative and
      quantitative agreement between the experimental and numerical results, suggesting
      that OpenFOAM is capable of predicting the main features of unsteady flow through
      a complex patient-based abdominal aortic aneurysm geometry. The intraluminal
      thrombus and arterial wall were then included, and solid stress and fluid
      structure interaction simulations were performed on this, and two other patient
      based abdominal aortic aneurysm geometries. It was found that the solid stress
      simulations resulted in an under-estimation of the maximum stress by up to 5.9%
      when compared with the fluid-structure interaction simulations. In the fluid
      structure interaction simulations, flow induced pressure within the aneurysm was
      found to be up to 4.8% higher than the value of peak systolic pressure imposed in
      the solid stress simulations, which is likely to be the cause of the variation in
      the stress results. In comparing the results from the initial fluid-only
      simulation with results from the fluid-structure interaction simulation on the
      same patient, it was found that wall shear stress values varied by up to 35%
      between the two simulation methods. It was concluded that solid stress
      simulations are adequate to predict the maximum stress in an aneurysm wall, while
      fluid-structure interaction simulations should be performed if accurate
      prediction of the fluid wall shear stress is necessary. Therefore, the decision
      to perform fluid-structure interaction simulations should be based on the
      particular variables of interest in a given study.

PMID- 22611870
TI  - Association of limited joint mobility and increased plantar hardness in diabetic
      foot ulceration in north Asian Indian: a preliminary study.
AB  - The aim of this article is to investigate the association of limited joint
      mobility and foot sole hardness in north Asian Indian type 2 diabetic patients.
      Limited joint mobility and hardness of the foot sole were measured for 39
      subjects attending the AIIMS Endocrinology & Metabolism Clinic. The total subject
      divided into three groups: 13 control subjects (nondiabetic), 13 diabetic
      patients without neuropathy and 13 diabetic neuropathy patients. Neuropathy
      status was assessed using 10 gm Semen's Weinstein monofilament. Joint mobility
      parameters, such as ankle dorsiflexion/plantar flexion and metatarsophalangeal-1
      dorsiflexion/plantar flexion, are measured using a goniometer. Foot sole hardness
      was measured using a durometer or shore meter. We found that diabetic patients
      with a neuropathic foot had significantly reduced joint mobility and increased
      foot sole hardness, placing them at risk for subsequent ulceration.
      Metatarsophalangeal-1 dorsiflexion/plantar flexion of both feet of diabetic
      patients had significant correlation (at p < 0.05, p < 0.001, p < 0.001 level)
      over age and body mass index. Also ankle plantar flexion/dorsiflexion and
      metatarsophalangeal-1 dorsiflexion/plantar flexion has a significant correlations
      (at p < 0.01, p < 0.05, p < 0.001, p < 0.001 level) with foot sole hardness in
      both feet of diabetic neuropathy subjects. Also linear regression analysis showed
      that duration of diabetes was significantly associated with the joint mobility
      parameters. In this study we conclude that joint mobility had reduced further if
      neuropathy and increased foot sole hardness coexisted owing to high plantar
      pressures. Hence, both limited joint mobility and increased foot sole hardness
      appears to be important determinants of foot sole ulceration in diabetic
      neuropathic subject.

PMID- 22611871
TI  - An intelligent method for identifying otological drill slippage.
AB  - An otological drill is a fundamental apparatus used for bone-milling in ear
      surgery. A common problem in bone-milling is that the drill bit slips on the bone
      surface. To improve the operational safety of such a surgery, this article
      presents a new apparatus combined with an intelligent method for identifying
      drill slippage. A two-axis force sensor is installed on a modified drill, and it
      detects the force of the bone's reaction to the drill bit. By integrating the
      unit reaction forces of the bone and the drill bit on the contact area, the
      functions of the force signals are deduced, which can reflect changes in the
      milling parameters. Based upon these functions, the slippage force, which is an
      important factor in drill slippage, is then extracted. An adaptive filter is
      specially designed to suppress interference in the slippage force. Drill slippage
      can be identified by calculating the variations in the filtering results. Five
      surgeons were invited to carry out an experiment in which they used this method
      on calvarian bones. Their average recognition rate of drill slippage was 86%, and
      only 1% of normal millings were identified as milling faults.

PMID- 22611872
TI  - Biomechanical measurements of axial crush injury to the distal condyles of human
      and synthetic femurs.
AB  - Few studies have evaluated the 'bulk' mechanical properties of human longbones
      and even fewer have compared human tissue to the synthetic longbones increasingly
      being used by researchers. Distal femur fractures, for example, comprise about 6%
      of all femur fractures, but the mechanical properties of the distal condyles of
      intact human and synthetic femurs have not been well quantified in the
      literature. To this end, the distal portions of a series of 16 human fresh-frozen
      femurs and six synthetic femurs were prepared identically for mechanical testing.
      Using a flat metal plate, an axial 'crush' force was applied in-line with the
      long axis of the femurs. The two femur groups were statistically compared and
      values correlated to age, size, and bone quality. Results yielded the following:
      crush stiffness (human, 1545 +/- 728 N/mm; synthetic, 3063 +/- 1243 N/mm; p =
      0.002); crush strength (human, 10.3 +/- 3.1 kN; synthetic, 12.9 < or = 1.7 kN; p
      = 0.074); crush displacement (human, 6.1 +/- 1.8 mm; synthetic, 2.8 +/- 0.3 mm; p
      = 0.000); and crush energy (human, 34.8 +/- 15.9J; synthetic, 18.1 +/- 5.7J; p =
      0.023). For the human femurs, there were poor correlations between mechanical
      properties versus age, size, and bone quality (R2 < or = 0.18), with the
      exception of crush strength versus bone mineral density (R2 = 0.33) and T-score
      (R2 = 0.25). Human femurs failed mostly by condyle 'roll back' buckling (15 of 16
      cases) and/or unicondylar or bicondylar fracture (7 of 16 cases), while synthetic
      femurs all failed by wedging apart of the condyles resulting in either fully or
      partially displaced condylar fractures (6 of 6 cases). These findings have
      practical implications on the use of a flat plate load applicator to reproduce
      real-life clinical failure modes of human femurs and the appropriate use of
      synthetic femurs. To the authors' knowledge, this is the first study to have done
      such an assessment on human and synthetic femurs.

PMID- 22611873
TI  - Development of an interlocked nail for segmental defects in the rabbit tibia.
AB  - Previous animal models have been developed to study intramedullary nailing for
      challenging segmental defects in the tibia. In large animals, interlocked nail
      fixation created a stable environment suitable to study new bone growth
      technologies placed in the defect. To our knowledge, there are no comparable
      interlocked tibial defect models for the rabbit in which new technologies could
      be evaluated. Such a model would be helpful since the rabbit is a popular initial
      model for orthopedic research studies owing to its wide availability and low
      cost. While numerous studies have nailed the rabbit tibia, all were non-locked
      implants that allowed some degree of instability between the fracture fragments.
      In addition, the non-locked nails were constructed of stainless steel, whereas
      human nails are increasingly made from titanium alloy. In the current study, an
      interlocked titanium nail was developed for the rabbit tibia. It was implanted in
      cadaver tibiae and subjected to fatigue cycling in combined compression and
      bending at physiologic levels to 21,061 cycles. This duration is estimated to
      represent 12 weeks of gait by the animal. Before and after fatigue cycling,
      monotonic testing was performed in compression and bending at physiologic levels.
      The intact contralateral limbs served as controls. All limbs completed the
      cycling; the instrumented limbs exhibited interfragmentary cyclic strain
      amplitudes during fatigue (616 +/- 139 micro-strain), which was significantly
      greater than the control limbs (136 +/- 35 microstrain). Monotonic strain
      amplitudes for the test limbs in bending and compression were 4839 +/- 1028 and
      542 +/- 122 microstrain, respectively; corresponding values for the control bones
      were 407 +/- 118 and 95 +/- 38 microstrain, respectively. These data are similar
      to those presented in prior studies in larger bone models. The current study
      presents one method for interlocked nail fixation for this complex tibial shaft
      fracture in a small animal.

PMID- 22611874
TI  - Computational analysis of blood clot dissolution using a vibrating catheter tip.
AB  - We developed a novel concept of endovascular thrombolysis that employs a
      vibrating electroactive polymer actuator. In order to predict the efficacy of
      thrombolysis using the developed vibrating actuator, enzyme (plasminogen
      activator) perfusion into a clot was analyzed by solving flow fields and species
      transport equations considering the fluid structure interaction. In vitro
      thrombolysis experiments were also performed. Computational results showed that
      plasminogen activator perfusion into a clot was enhanced by actuator vibration at
      frequencies of 1 and 5 Hz. Plasminogen activator perfusion was affected by the
      actuator oscillation frequencies and amplitudes that were determined by
      electromechanical characteristics of a polymer actuator. Computed plasminogen
      activator perfused volumes were compared with experimentally measured dissolved
      clot volumes. The computed plasminogen activator perfusion volumes with threshold
      concentrations of 16% of the initial plasminogen activator concentration agreed
      well with the in vitro experimental data. This study showed the effectiveness of
      actuator oscillation on thrombolysis and the validity of the computational
      plasminogen activator perfusion model for predicting thrombolysis in complex flow
      fields induced by an oscillating actuator.

PMID- 22611875
TI  - Investigation of the compressive stiffness of spinal cages in various
      experimental conditions based on finite element analysis.
AB  - Recently, novel polymers, including polyetheretherketone and carbon fibre
      reinforced polymer, have been used for spinal implants. Because the in vitro
      experimental test uses metal blocks with different material properties from those
      of polymer cages in standard test protocols for prediction of the mechanical
      performance, it is necessary to analyse the influence of various experimental
      conditions, such as the material of the blocks. In this study, the compressive
      stiffness of spinal cages was investigated for different materials
      (polyetheretherketone, carbon fibre reinforced polymer, and titanium) under
      simulations of the mechanical experimental tests and the in vivo situation based
      on finite element analysis. The stiffness was affected by shapes of cage as well
      as experimental conditions, such as the load application method or fixation
      block. In the open cages, the polymer cages showed a greater dependence on the
      experimental situation than the metal cages. Hence, it may be necessary to
      consider the experimental conditions during in vitro mechanical tests for the
      stiffness evaluation of spinal cages made of novel polymers to obtain results
      relevant for an in vivo situation.

PMID- 22611876
TI  - [No to "avoidable hospitalization" as performance compensation].

PMID- 22611877
TI  - [Cheaper drugs without environmental considerations can cost us dearly. Sweden
      proposes tightening of international regulations to reduce emissions].

PMID- 22611878
TI  - [Mapping of protective factors in type 1 diabetes has begun. Some patients appear
      to be protected against late complications--Several studies are underway].

PMID- 22611879
TI  - [Emissions from the pharmaceutical industry affects the environment. Antibiotic
      emissions also jeopardizes our own health].

PMID- 22611880
TI  - [Transfusions of older blood products may pose a risk. Knowledge of storage and
      transfusion-related injuries is unclear].

PMID- 22611881
TI  - [Upper airway obstruction caused by ACE inhibitor-induced angioedema].

PMID- 22611882
TI  - [Drugs and the environment in practice. What can counties and regions to do?].

PMID- 22611884
TI  - [Understanding the silence].

PMID- 22611883
TI  - [Beautiful writing--without hands].

PMID- 22611885
TI  - [A memory outpatient clinic in Martinique].
AB  - The ageing of the population is resulting in a growth in chronic physical and/or
      psychological pathologies, including Alzheimer's disease which progresses
      relentlessly with age. Lamentin hospital in Martinique has created a memory
      outpatient clinic in order to accelerate awareness raising, training and
      diagnosis.

PMID- 22611886
TI  - [Snoezelen and animal-assisted therapy in dementia patients].
AB  - A number of non medication-based methods of nursing care for geriatric patients
      have been developed over recent decades to treat non cognitive symptoms
      associated with dementia. Among these, Snoezelen rooms for multisensory
      behavioural therapy and animal-assisted therapy emerge as innovative strategies
      which could potentially complement other more frequently developed methods such
      as physical activity.

PMID- 22611887
TI  - [Example of frailty scores in a mobile geriatrics team].
AB  - The mobile geriatrics team of Espalion-Saint-Laurent-d'OIt inter-municipal
      hospital works with frail elderly people in order to optimise their care. It is
      with this objective in mind that the mobile team decided to create a tool to
      assess the degree of frailty of the people being monitored.A study of the frailty
      scores recorded during 2010 and an analysis of the results could thereby be
      carried out.

PMID- 22611888
TI  - [Social isolation in the elderly dementia patient].

PMID- 22611889
TI  - [Landscaper of hospital property. Interview by Elisabeth Rogez].

PMID- 22611890
TI  - [A family confronted with aging].

PMID- 22611891
TI  - [Family help for frail elderly: challenges and perspectives].
AB  - The current support available for frail elderly people, meaning those facing a
      number of physical and psychological dependencies, is the fruit of relatively
      recent and diverse transformations. The reconstitution of social relations over
      the last fifty years, the development of social policies and those relating to
      risk prevention, notably in the area of public health, and the enactment of new
      lifestyle standards have resulted in a significant increase in life expectancy.

PMID- 22611892
TI  - [Family carers, dependent elderly people and access to care].
AB  - The issue of carers of dependent elderly people is of significant importance in
      our present day society. Mobilised and committed, they are responsible for the
      elderly person's dignity and care sometimes risking burnout or a tendency to
      inappropriate treatment. This informal help must be adapted to avoid such
      potential problems. The delegation of tasks must remain the responsibility of
      qualified professionals.

PMID- 22611893
TI  - [The residents and relatives committee in nursing homes].
AB  - The residents and relatives committee is an area for exchange and expression
      concerning the running of the facility or unit caring for a resident. It is an
      important body which places the user at its centre but which can however reveal
      disparities in the way it operates.

PMID- 22611894
TI  - [The role of families when a relative enters a nursing home].
AB  - The role of the family is essential in the process of admitting someone to a
      nursing home in order to prevent the future resident from feeling abandoned.
      Elderly people are more likelyto adapt to their new environment when the family
      is involved in this choice and has guided them through the process.

PMID- 22611895
TI  - ["When Christiane arrived at my house..."].

PMID- 22611896
TI  - [Family ties and maintenance obligation].
AB  - Maintenance obligation is a question frequently addressed in gerontology as an
      elderly person prepares to enter an institution. Its implementation is a source
      of conflict within families as well as with professionals involved in these
      situations. This administrative process, generally long and complex, can shatter
      family ties and lengthen the time required to obtain support thereby delaying
      admission to the institution. To tackle these issues, professionals from the
      Paris Saint-Joseph hospital group have set up meetings bringing together social
      services, medical services and management representatives. These multi
      disciplinary consultations have highlighted the need for management to work with
      the families of hospitalised patients to remind them of the maintenance
      obligation in a framework of mediation.

PMID- 22611897
TI  - [Bibliography - family and the elderly].

PMID- 22611898
TI  - [Nail diseases in the elderly].

PMID- 22611899
TI  - Long-term dental implant success and survival--a clinical study after an
      observation period up to 6 years.
AB  - The aim of the present work was to evaluate the long-term results of dental
      implants and the risk factors associated with implant survival and success rates.
      108 patients were examined and the control consisted of medical history taking,
      clinical and radiographic examinations. The survival rate of dental implants was
      96.0% and the success rate was 94.3%. Mucositis was found to be related to
      patients' age and the number of implant units placed. Peri-implantitis was often
      found in patients showing low standards of oral hygiene as well as in those who
      were not coming on regular dental visits. Mucositis was in every 5th implant site
      and was mostly seen in patients with prosthetic constructions consisting of 3 or
      more units as well as in older patients. Oral hygiene and dental control visits
      are important to maintain good oral health.

PMID- 22611900
TI  - Patient attitudes and expectations of dental implant treatment--a questionnaire
      study.
AB  - The aim of the present study was to evaluate patient attitudes and expectations
      relative to dental implant treatment. A questionnaire was mailed to all 400
      patients that had received dental implant treatment at a large multi-specialist
      clinic during 2008. The questionnaire included questions relative to the reasons
      for dental implant treatment, if the patient earlier had considered dental
      implants, expectations of the treatment, discomfort during and after surgery, and
      how the patient perceived the esthetic outcome. The response rate was 61% (114
      men/130 women). The stated reason for tooth loss was in 50% of the patients
      periodontitis,19% caries, 8% accidents,13% other reasons, and 10% no stated
      reason. Almost all patients (96%) were satisfied with the esthetic appearance and
      also regarding the information of the treatment (94%). Regarding the time between
      surgery and completion of prosthetic work, 79% (n = 192) found it to be
      reasonable. 71% (n = 170) thought the cost was what they had expected. 47% of the
      patients experienced the implant surgery better than expected and 48% as
      expected. In conclusion, the present study revealed that almost all patients were
      satisfied with the function and esthetics of the dental implant reconstruction
      and most patients were also satisfied regarding the costs and treatment duration.

PMID- 22611901
TI  - Clinical routines and management of suspected child abuse or neglect in public
      dental service in Sweden.
AB  - Mandatory reporting to the social services is required by dental professionals
      when suspicion of child abuse or neglect occurs. The objective of this study was
      to analyze the recommendations previously made by the Ombudsman for Children in
      Sweden. The aim was to study the association between having guidelines and the
      inclination to report to the social services and also the association between
      management of multiple missed appointmens and reports to the social service. A
      web-based questionnaire was sent to the clinical department heads (CDH) of all
      PDS in Sweden, distributed and authorized by The Ombudsman for Children in
      Sweden. The response frequency was 95% and all county councils of Sweden were
      represented. The results showed regional differences regarding management of
      suspected child abuse, neglect and dental neglect. Clinical department heads that
      had reported to the social services more often had guidelines on child abuse and
      neglect (p < 0.000). Management of repeated missed appointments varied between
      clinics. Those who never had made a report to the social services more often
      stated that the reason for missed appointments was parental negligence (p =
      0.004) and less often thought it was an actual maltreatment (p = 0.003), and they
      more often rescheduled when a child repeatedly missed an appointment (p = 0.013).
      Sixty-four percent of the clinical department heads requested additional support
      in this matter. In conclusion, public dental service clinics in Sweden are
      significantly more likely to report to the social services if guidelines
      regarding child abuse and neglect are available.

PMID- 22611902
TI  - Comparing patients with Apert and Crouzon syndromes--clinical features and cranio
      maxillofacial surgical reconstruction.
AB  - Cranio-maxillofacial malformations, as seen in Crouzon and Apert syndromes, may
      impose an immense distress on both function and aesthetics of the person
      affected. The aims of this study were to describe and compare the main facial and
      intraoral features of patients with Apert and Crouzon syndromes, the clinical
      manifestations that may be present, additionally to the main syndromic traits, as
      well as the cranio-maxillofacial surgical treatment protocols followed.Twenty
      three patients with Apert syndrome (6 males, 17 females), and 28 patients with
      Crouzon syndrome (20 males, 8 females) were evaluated for general medical
      aspects, craniofacial characteristics, dentoalveolar traits before and after the
      final orthognathic surgery, and types and timing of cranio-maxillofacial
      operations. Mental retardation, associated additional malformations, cleft
      palate, and extensive lateral palatal soft tissue swellings were more common in
      children with Apert syndrome. In both syndromes, clinical findings included
      concave profile, negative overjet, posterior crossbites, anterior openbite, and
      dental midline deviation, which were corrected in almost all cases with the final
      orthognathic surgery, with the exception of the lateral crossbites, including
      more than one tooth pair, which were persisting in about half of the cases.
      Cranial vault decompression and/or reshaping, midfacial and orbital advancement
      procedures, often in conjunction with a mandibular setback, were the most
      frequent cranio-maxillofacial operations performed. In conclusion, Apert syndrome
      is more asymmetric in nature and a more severe clinical entity than Crouzon
      syndrome. The syndromic dentofacial features of both conditions could be
      significantly improved after a series of surgical procedures in almost all cases
      with the exception of the posterior crossbites, with haIf of them persisting post
      surgically.

PMID- 22611903
TI  - Bed partners' and patients' experiences after treatment of obstructive sleep
      apnoea with an oral appliance.
AB  - The purpose of the study was to evaluate bed-partners' and patients' self-reports
      of general well-being, physical strength and mental energy after treatment for
      obstructive sleep apnoea (OSA) with a mandibular advancement oral appliance (OA).
      Patients (N = 134) referred from medical physicians diagnosed with true OSA, i.e.
      an apnoea-hypopnoea index of > 10, were treated with an OA for more than one
      year. The somnographic evaluations were undertaken in a patient's home before the
      start of, and six months after, treatment. An individually designed monobloc OA
      was manufactured by a dental technician for nightly use. After one year of
      treatment, a follow-up questionnaire was sent to patients whose sleep disorder
      was reduced > 50% from baseline values and to their bed partners. The
      questionnaire consisted of 15 questions or statements with multi-answer
      alternatives concerning well-being, physical strength, mental energy, sleep, day
      and night symptoms, and the Epworth Sleepiness Scale (ESS: eight questions). The
      questionnaire was answered by 82% (110/134) of the patients and 85 bed partners.
      Both patients and bed partners reported improvement in general well-being,
      physical strength and mental energy, between 70-80% for patients and 55-68% for
      bed partners sharing the same bed-room. Similar results were found for
      concentration ability, joyfulness and strength of effort in social intercourse,
      as well as decreased daytime sleepiness, improvement in the feeling of getting
      enough sleep and reduced nocturia. CONCLUSIONS: In all dimensions, the treatment
      effect had a great influence, not only on patients but on bed partners as well.

PMID- 22611904
TI  - Tobacco cessation interventions by Swedish dental hygienists--a questionnaire
      study.
AB  - The aim of the study was to investigate tobacco cessation interventions by
      Swedish dental hygienists and their perception of the importance of tobacco
      cessation to oral health. A questionnaire was mailed to 400 randomly selected
      dental hygienists (DH) in Sweden. The questions covered such topics as tobacco
      cessation interventions, perceived barriers, and their perception of the
      importance of tobacco cessation in relation to caries, gingivitis, periodontitis
      and dental implants. The response rate was 57%. Tobacco habits were routinely
      recorded by 94% of the respondents. 52% of the dental hygienists reported time
      constraints, 50% reported insufficient competence and 43% answered that they had
      lack of experience to work with tobacco cessation. All respondents perceived
      tobacco cessation to be an important determinant of treatment outcomes in
      patients with dental implants and periodontitis. Bivariate analysis showed an
      association between training courses in tobacco cessation and tobacco cessation
      interventions (OR 3.25, CI 95% 1.80-5.85). A logistic multivariate regression
      model disclosed two other factors significantly correlated with tobacco cessation
      interventions: competence (OR 2.4, 95% CI 1.16-4.85), and experience (OR 2.1, 95%
      CI 1.06-4.28). The analyses were adjusted for age, length of undergraduate
      training course, and dental care organization. The dental hygienists considered
      tobacco cessation to be very important in patients with periodontitis and in
      those with dental implants. Most of the DH in this study undertook some tobacco
      cessation interventions, though not extensive; the main barriers reported were
      lack of time, competence and experience.

PMID- 22611905
TI  - Use of different mouthrinses in an adult Swedish population.
AB  - The purpose of this study was to evaluate the use of mouthrinse products in a
      Swedish adult population and the factors that influence their use. A
      questionnaire, comprising semi-closed questions focusing on mouthrinses for oral
      health, was distributed to randomly selected 700 individuals aged 17-94 years
      (final response rate of 60%). The data revealed that 47% of the individuals use a
      mouthrinse product on a regular basis and that it does not differ significantly
      due to age. Women use such products to a greater extent than men. Individuals who
      brush their teeth and who use approximal cleaning aids frequently appear to use
      mouthrinse products to a greater degree. Rinsing is primarily performed once a
      day or more (45%), in the evening (57%) and after brushing (87%). Those
      individuals that have been recommended to use the products by dentists and dental
      hygienists use them to a greater degree (78%) than those who have not received
      any recommendations (27%). Apart from dental personnel, advertising also plays a
      significant role in product selection. Of the different products available on the
      market, pure fluoride products constitute 46%. To summarise, this study indicates
      that a Swedish adult population, especially women, uses mouthrinse products to a
      relatively large extent, mainly as a supplement to other oral hygiene procedures
      such as brushing with a fluoride toothpaste twice daily. To select the most
      suitable product, the dental personnell should play a more active role in
      recommendations to the patients who need or want to use mouthrinses.

PMID- 22611906
TI  - [Reform of forensic autopsy in the German Code of Criminal Procedure].
AB  - The Federal Ministry of Justice has presented another proposal to rephrase the
      wording of Section 87 of the German Code of Criminal Procedure (StPO). The new
      version of Section 87 StPO is to be rejected as it would lead to a loss of
      institutional and professional standards. The bill is clearly influenced by a
      tendency towards privatisation for the benefit of a small group of specialists in
      forensic medicine mostly organised in limited liability companies and thus at the
      expense of institutes of legal medicine affiliated to universities or physicians
      working in the forensic service of regional courts. In the long run, this reform
      would not only jeopardize medicolegal research and teaching but also medical
      education and specialist medical training. For future severe negative
      consequences would have to be expected on the rule of law and legal certainty.

PMID- 22611907
TI  - [Fatal crossbow injury in an adolescent].
AB  - The authors present the case of a 14-year-old boy who died while handling a
      crossbow, which was a gift from a friend's mother. The bolt passed through the
      right nostril, penetrated the sinus sphenoidalis, the brain stem, the left
      occipital lobe and the occipital calvaria. Immediately after the accident, the
      victim was taken to a maximum care hospital. In spite of neurosurgical treatment
      and intensive care the victim died 4 days later. The case presented demonstrates
      that crossbows are not suitable as toys for underage persons, as they are deadly
      weapons which can cause serious penetrating injuries. In Germany, no license is
      required to buy and/or possess crossbows. In the authors' opinion, legal
      restrictions on the sale of crossbows and a special training of the users would
      be reasonable measures to reduce such accidents.

PMID- 22611908
TI  - ["Natural" death of a person under the care of a custodian].
AB  - An ambulance service doctor was called to the death of a 76-year-old woman and
      attested cardiac arrest and psycho-organic brain syndrome as the cause of death
      on the death certificate. At the second external examination mandatory before
      cremation, extensive hematomas were detected on the right thorax and multiple
      haematomas in the face and on the forehead. The autopsy initially ordered by the
      public health officer revealed serial rib fractures and a fractured skull. After
      notifying the prosecutor, a forensic autopsy was ordered and death was found to
      have been caused by fat embolism following massive blunt force to the thorax with
      serial rib fractures and haematopneumothorax. After that, the adopted son, who
      had been appointed care custodian for the woman, and his wife were suspected,
      because they had given contradictory explanations for the injuries. At first,
      they were only suspected of failure to render assistance, but in the end they
      were both charged with murder. Only because of the second external examination
      prescribed by the law still in force could the errors of the improper first
      external examination be corrected.

PMID- 22611909
TI  - [Informed consent to postmortem tissue donation: a catamnestic survey within a
      year of the donor's death].
AB  - The authors present data from 36 musculoskeletal donors. Talking to the next of
      kin plays a key role in the consenting process for tissue donation. We give an
      overview of our fundamental thoughts and the guidelines developed for the contact
      with the family and present the results of a catamnestic review. METHODS: One
      year after procurement, we contacted the consenting persons by telephone for an
      interview using a semi-standardized questionnaire to evaluate the information
      given on tissue donation and the emotional processing of the death. RESULTS: 8-18
      months after the donation, 26 (72.2 %) consenting persons could be reached and
      gave a positive feedback with regard to the information and support provided and
      the consent given by them at that time. DISCUSSION: The telephone contact of
      physicians from an Institute of Legal Medicine with the family of a deceased is
      perceived as being helpful in an acute stress situation caused by a sudden death
      and as an accepted way to ascertain the deceased's last will with regard to a
      potential musculoskeletal donation. According to the German Transplantation Act
      asking for musculoskeletal donations is the duty of every physician. Our data
      show that this does not constitute an additional burden for the relatives, if the
      question is asked in an appropriate way.

PMID- 22611910
TI  - [Sexual assaults in Geneva between 2006 and 2010].
AB  - In Geneva, all sexual assault victims are examined both by a gynaecologist and a
      forensic pathologist with special training in clinical forensic medicine. Between
      2006 and 2010, 473 victims were examined following such an assault. Over the
      years, the number of sexual assaults rose steadily. Most victims were aged
      between 15 and 30 years. The majority of the assaults occurred at night and on
      the weekend and often happened at the place where the perpetrator or the victim
      lived. Usually, the offender acted alone and was known to the victim. Many
      victims hesitate to present for an examination, which makes it difficult to
      collect evidence. Penetration was usually vaginal and without the use of a
      condom. Injuries on the body or genitals were seen in only half of the cases for
      the first ones and in less than one third for the second ones. Quite often (at
      least in 42 % of the cases), the victim consumed alcohol before the assault and
      the use of drugs--especially cannabis--was not uncommon either.

PMID- 22611911
TI  - [Criminology and superstition at the turn of the 19th century].
AB  - Criminology, which institutionalised at university level at the turn of the 19th
      century, was intensively engaged in the exploration of superstition.
      Criminologists investigated the various phenomena of superstition and the
      criminal behaviour resulting from it. They discovered bizarre (real or imagined)
      worlds of thought and mentalities, which they subjected to a rationalistic regime
      of interpretation in order to arrive at a better understanding of offences and
      crimes related to superstition. However, they sometimes also considered the use
      of occultist practices such as telepathy and clairvoyance to solve criminal
      cases. As a motive for committing homicide superstition gradually became less
      relevant in the course of the 19th century. Around 1900, superstition was
      accepted as a plausible explanation in this context only if a psychopathic form
      of superstition was involved. In the 20th century, superstition was no longer
      regarded as an explanans but an explanandum.

PMID- 22611912
TI  - Quinazolinone exposure induces apoptosis and changes expressions of Fas/FasL and
      C-Flip in embryonic mice testicles.
AB  - Quinazolinones represent a class of sedative and anticancer drugs. Quinazolinones
      based compounds have ability to suppress prostate tumor growth via apoptosis.
      Apoptosis is very common in embryos and adults of normal and injured mammalian
      testes. Effects a new derivative of quinazolinone (4(3H) quinazolinone-2-ethyl-2
      phenyl ethyl (QEPE)), on the testis of Balb/C mice embryos were investigated.
      QEPE was able to reduce number of germ cells and diameter of seminiferous
      tubules. TUNEL assay analysis indicated that reduction correlated with an
      increase in the number of apoptotic cell. Furthermore, electron microscope
      observations confirmed typical apoptotic morphologies characterized by chromatin
      fragmentation. Finally, RT-PCR analysis showed QEPE increases the levels of
      Fas/Fasl and decreases C-Flip mRNAs in the testis of exposed embryos.

PMID- 22611913
TI  - Purification of recombinant antigen BmSXP used in panLF rapid kit for lymphatic
      filariasis.
AB  - A rapid antibody detection test is very useful for the detection of lymphatic
      filariasis, especially for certification and surveillance of post-mass drug
      administration. panLF Rapid kit is suitable for this purpose since it can detect
      all species of lymphatic filaria. It is based on the detection of anti-filarial
      IgG4 antibodies that react with recombinant B. malayi antigens, BmR1 and BmSXP.
      There is an increase demand for the test due to its attributes of being rapid,
      sensitive and specific results, as well as its field-applicability. The main aim
      of this paper is to obtain high recovery and purity of recombinant antigen BmSXP
      via a modified method of immobilized metal affinity chromatography (IMAC). The
      highest product yield of 11.82 mg/g dry cell weight (DCW) was obtained when IMAC
      was performed using the optimized protocol of 10 mM imidazole concentration in
      lysis buffer, 30 mM imidazole concentration in wash buffer, and 10 column volume
      wash buffer containing 300 mM salt concentration. This gave a 54% protein
      recovery improvement over the manufacturer's protocol which recorded a product
      yield of only 7.68 mg/g DCW. The recovered BmSXP recombinant antigen showed good
      western blot reactivity, high sensitivity (31/32, 97%) and specificity (32/32,
      100%) in ELISA, thus attesting to its good purity and quality.

PMID- 22611914
TI  - Mosquito cell line C6/36 shows resistance to Cyt1Aa6.
AB  - This study aimed to investigate the resistance mechanism of C6/36 cells to
      Cyt1Aa6 protein under selection pressure. Receptor binding properties of Cyt1Aa6
      toward sensitive and resistant C6/36 cells were investigated. More sensitive
      cells were detected with goat-anti-rabbit-FITC-labeled antibody, and the quantity
      of in vitro activated Cyt1Aa6 toxin bound to resistant cells was greatly reduced.
      Ligand western blot assays showed that disappearance of the 26 kDa protein and
      weakness of the positive bands of 68 kDa from resistant cells might lead to the
      resistance of C6/36 cells to Cyt1Aa6 toxin. The resistance of C6/36 cells was
      detected under selection in vitro-activated Cytl1Aa6 toxin. Receptor binding
      demonstrated that reduced Cyt1Aa6 bound to resistant cells, which might be
      closely related to the disappearance and weakness of some proteins. The results
      presented here are the first to demonstrate that Cyt1Aa protein, a uniquely
      characteristic toxin, induced resistance at the cellular level. It might be
      attributed to the change of receptors.

PMID- 22611915
TI  - Immunomodulatory effects of alcbholic and hydroalcoholic extracts of Moringa
      olifera Lam leaves.
AB  - Effects of 50, 100 and 200 mg/kg body weight of the alcoholic and hydro-alcoholic
      extract of leaves of M. olifera were studied on various immune paradigms like
      delayed type hypersensitivity reaction using SRBC as an antigen, determination of
      antibody titer, neutrophil adhesion test as an indicator for neutrophil index,
      total leucocyte count in cyclophosphamide induced immunosuppressed animals and
      carbon clearance assay as a measure of phagocytic activity. Hydro-alcoholic
      extract of M. olifera substantially enhanced cellular immune response, humoral
      immune response, neutrophil index and phagoctic activity in doses of 100 and 200
      mg/kg body weight. The ethanolic extract (200 mg/kg body weight) was efficient in
      improving immune response. The results suggest that M. olifera has a significant
      role to play as an immune stimulator.

PMID- 22611916
TI  - Wound healing activity of ethanolic extract of Shorea robusta Gaertn. f. resin.
AB  - The ethanolic extract of S. robusta resin (10 and 30 % w/w applied locally in
      excised and incised wounds) produced a dose-dependent acceleration in wound
      contraction and increased hydroxyproline content and tensile strength of wounds
      in rats. The results demonstrate wound healing activity of ethanolic extract of
      S. robusta resin.

PMID- 22611917
TI  - Rapid screening and cultivation of oleaginous microorganisms.
AB  - Oleaginous microbial strains were cultivated to identify the best oil-producing
      strain amongst Yarrowia lipolytica (CGMCC 2.1398), Lipomyces starkeyi (CGMCC
      2.1608), Rhodosporidium toruloides (CGMCC 2.1389), Mortierella isabellina (CGMCC
      3.3410), Cunninghamella blakeleana (CGMCC 3.970), and Mycobacterium QJ311. A
      method for rapid determination of oil content and fatty acid composition was
      established to identify the optimum oil-producing strains. This method had a
      relative standard deviation of 4.09%, an average recovery ratio of 97.09% and a
      detection limit of 0.1-1.0 g. Mortierella isabellina CGMCC 3.3410 was identified
      as the best oil-producing strain amongst the six strains tested, with a total
      biomass of 75 g/10 L and a lipid content of 35%. A rapid screening method of
      oleaginous microorganisms is discussed for the first time.

PMID- 22611918
TI  - Decolourization and degradation of C.I.Reactive Red 195 by Georgenia sp.CC-NMPT
      T3.
AB  - Azo dye Reactive Red 195 was selected for decolourization and degradation studies
      by Georgenia sp.CC-NMPT-T3. Optimization of parameters for dye decolourization
      was studied under static anoxic condition. Under optimized condition
      decolourization of Reactive Red 195 by Georgenia sp.CC-NMPT-T3 was found to be
      95.93 % at 50 mg/L within five hours in static anoxic condition. The optimum pH
      and temperature for the decolourization was 7.0 and 40 degrees C respectively.
      The biodegradation was monitored by UV-Vis, and TLC and HPLC. Toxicity study
      demonstrated no toxicity of the biodegraded product. The results suggest that the
      isolated organism Georgenia sp.CC-NMPT-T3 as a useful tool to treat wastewater
      containing reactive dyes.

PMID- 22611919
TI  - Cadmium tolerance and antibiotic resistance in Escherichia coli isolated from
      waste stabilization ponds.
AB  - The incidence pattern of cadmium tolerance and antibiotics resistance by
      Escherichia coli was examined periodically from the samples of water, sludge and
      intestine of fish raised in waste stabilization ponds in a sewage treatment
      plant. Samples of water and sludge were collected from all the selected ponds and
      were monitored for total counts of fecal coliform (FC), total coliform (TC) and
      the population of Escherichia coli, which was also obtained from the intestine of
      fishes. Total counts of both FC and TC as well as counts of E. coli were markedly
      reduced from the facultative pond to the last maturation pond. Tolerance limit to
      cadmium by E. coli tended to decline as the distance of the sewage effluent from
      the source increased; the effective lethal concentration of cadmium ranged from
      0.1 mM in split chamber to 0.05 mM in first maturation pond. E. coli isolated
      from water, sludge and fish gut were sensitive to seven out of ten antibiotics
      tested. It appears that holistic functions mediated through the mutualistic
      growth of micro algae and heterotrophic bacteria in the waste stabilization ponds
      were responsible for the promotion of water quality and significant reduction of
      coliform along the sewage effluent gradient.

PMID- 22611920
TI  - [Effect of PARP-1 inhibitor 4-amino-1 ,8-naphthalimide on the on the sensitivity
      of adriamycin].
AB  - OBJECTIVE: To explore the effect of inhibition of poly (ADP-ribose) polymerase-1
      (PARP-1) on the sensitivity of cells to adriamycin (ADM). METHODS: Mouse
      embryonic fibroblasts (MEFs) were divided into two groups according to whether
      they were treated with 4-amino-1,8-naphthalimide (4-AN) or not. And then the
      differences of cell viability and genotoxicity between the 4-AN treatment group
      and the non-treated group were compared after exposure to ADM. RESULTS: The half
      inhibitory concentrations of ADM (IC50) in the 4-AN treatment group was
      significantly lower than the non-treated group (P < 0.05). At 0.025-0.2 microg/ml
      concentration of ADM, the cell viability of the treatment group was significantly
      lower than that of the non-treated group (P < 0.05). Moreover, the population
      doubling time and the colony formation rate were significant longer or higher (P
      < 0.05) at 0.05-0.2 microg/ml concentration of ADM. Results from the comet assay
      and micronucleus assay showed that the doses of ADM increased, the comet rate,
      tail length, Olive tail moment, frequency of micronucleated cells and frequency
      of micronucleus formation of the both groups increased. At 0.02-1 microg/ml
      concentration of ADM, the comet rate, tail length, Olive tail moment of the
      treatment group were significant higher than those of controls (P < 0.05), and at
      0.01-0.2 microg/ml concentration of ADM, both the frequency of micronucleated
      cells and the frequency of micronucleus formation were significantly increased (P
      < 0.05). CONCLUSION: Inhibition of PARP-1 can significantly increase the
      sensitivity of cells to adriamycin, and DNA damage and repair may be a potential
      mechanism for this effect.

PMID- 22611921
TI  - [Effects of polychlorinated biphenyl on the expression of c-fos and c-jun in
      mesenchymal cells of rats].
AB  - OBJECTIVE: To study the effects of polychlorinated biphenyl (PCB126) on the
      expression of c-fos and c-jun in mesenchymal cells (MSCs) of rats. METHODS: MSCs
      were separated by percoll cell separating medium (density 1.073 g/cm3). After
      being cultured and transferred, the cells were divided into a control group, a
      low-dose group (10(-7) mol/L PCB126) and a high-dose group (10(-6) mol/L PCB126).
      The cellular growth rate and the expression of c-fos and c-jun protein were
      analyzed by MTT, immunofluorescence chemical assay, RT-PCR and Western blot.
      RESULTS: The cellular growth rate in the low-and high-dose group were 13.8% and
      19.1% at 12 h, 31.5% and 36.1% at 24 h, 42.5% and 43.6% at 48 h, respectively (P
      < 0.01). The positive rates of c-fos expression in the low-and high-dose groups
      were 54.6% and 51.3% at 12 h, and 83.2% and 73.0% at 24 h. The expression of c
      fos mRNA detected by RT-PCR was upregulated at 30 min and 1h in PCB126 groups.
      The expression of c-jun mRNA were much higher in PCB126 groups than that in the
      control group. The expression of c-fos and c-jun protein was upregulated in the
      low-and high-dose groups at 12 h and 24 h. CONCLUSION: PCB126 could promote the
      proliferation of MSCs and upregulate the expression of cancer associated gene c
      fos and c-jun. The effect of PCB126 on the function of MSCs might be associated
      with the abnormal expression of c-fos and c-jun gene.

PMID- 22611922
TI  - [Effects of selenium and zinc on the proliferation of human esophageal cancer
      cell line studied by serophysiology].
AB  - OBJECTIVE: The effect of serum from rats supplemented with selenium and zinc on
      the proliferation of human esophageal cancer cell line Eca109 was observed by
      serophysiology. METHODS: Rats were randomly divided into seven groups. Eight rats
      in each group were fed with basic feeds (deprived of both selenium and zinc). The
      experimental rat groups were supplemented with selenium or zinc at low or high
      dosage intragastrically for 30 days Serum selenium and zinc content of rats was
      measured by Graphite Furnace Atomic Absorption Spectrometry (GFAAS) and Flame
      Atomic Absorption Spectrophotometry (FAAS). MTT assay,3H-TDR incorporation and
      flow cytometry were used to explore the effect of serum from different rat groups
      on the growth and proliferation of cancer cell line Ecal09 cells. RESULTS: (1)
      The content of serum zinc in the high zinc group was the highest and the content
      of serum zinc was the lowest in basic diet group. The content of serum selenium
      in high selenium and high zinc group was the highest and the content of serum
      selenium was the lowest in the basic diet group. (2) In comparing the growth of
      control cancer cell group cultured with calf serum, the growth of cancer cells
      cultured with the serum from high selenium and high zinc rats was inhibited in
      culturing for 72 h, but the growth of normal liver cells were also inhibited. The
      growth of cancer cells were promoted by serum from other groups. (3) Both MTT
      assay and 3H-TDR incorporation test showed that the DNA synthesis in cancer cells
      was inhibited by the serum from high selenium and high zinc group, but the DNA
      synthesis of normal liver cells was also inhibited by this type of serum. The
      result of DNA synthesis in other cell groups was closed to the control group.
      CONCLUSIONS: Low serum selenium and zinc might promote the growth of EC cell.
      Elevating the content of serum selenium and zinc by increasing selenium and zinc
      intake might inhibit EC cell proliferation.

PMID- 22611923
TI  - [Protective effect of ALA on high glucose induced cellular injury of LLC-PK1
      cell].
AB  - OBJECTIVE: Made LLC-PK1 damage model induced by high glucose and observing the
      protection effect and its mechanisms of LLC-PK1 injury induced by high glucose.
      METHODS: The proliferation of LLC-PK1 induced by high glucose was tested by CCK-8
      and the apoptosis rat and the contents of reactive oxygen species (ROS) of LLC
      PK1 damaged by high glucose was observed by flow cytometry after administration
      of different concentration alpha-linolenic acid (ALA). RESULT: High glucose could
      obviously inhibit the proliferation of LLC-PK1 The apoptotic rates of LLC-PK1
      intervened by ALA (50-100 micromol/L) in the preconditioning group and the
      persistent intervention group were lower than those in the positive control group
      (P < 0.05). The contents of ROS of LLC-PK1 in the persistent intervention group
      were lower than those in the positive control group when the concentration of ALA
      were from 10 micromol/L to 100 micromol/L (P < 0.05, P < 0.01). The contents of
      ROS of LLC-PK1 in the preconditioning group were lower than those in the positive
      control group when the concentration of ALA was 50 micromol/L (P < 0.05).
      CONCLUSION: The model of LLC-PK1 induced by high glucose provided fine chances
      for the intervention of renal tubular epithelial cells in DN. ALA were expected
      to be a protectant to prevent high glucose damage of renal tubulars. Decreasing
      the active oxygen generation may be one of the mechanism of the protective
      effects on LLC-PK1 by ALA.

PMID- 22611925
TI  - [Oxidative damage and immunotoxicity effect of people who exposed to electronic
      waste].
AB  - OBJECTIVE: To investigate the relationship between risk factors and the effects
      of antioxidation and immune function in adults who exposed to electronic waste( e
      waste). METHODS: The exposed group was chosen from the people who lived in the e
      waste disposing areas of Zhejiang province. The control group was chosen from
      people who lived in unpolluted area. Anticoagulation and coagulation peripheral
      venous blood samples were collected from 40 exposed persons (22 employees, 18 non
      employees) and 36 exposed persons respectively. The oxidative, immune, Cd, Pb,
      Cr, Hg, and PCB indexes were detected. RESULTS: The contents of Cd, total PCB,
      MDA statistically increased in exposed group comparing with the control group (P
      < 0.05). The activity of SOD, GSH-Px, the percentage of helper/inducer T
      lymphocytes (CD4+) and the content of Cr in exposed group were less than those in
      the controlgroup (P < 0.05). CONCLUSION: Oxidative damage and immunotoxicity were
      observed in the group that lived in e-waste disposing areas. These effects were
      mainly related to the increase of Cd content or Cd and Pb contents in peripheral
      venous blood.

PMID- 22611926
TI  - [Overview and analysis of food chemical contaminant monitoring in 2000-2009 in
      China].
AB  - OBJECTIVE: To know about food safety situation and provide scientific data for
      the development of food safety policies and laws. METHOD: Monitoring task was
      carried out in some areas of China by some measures and steps such as formulating
      plan, compiling SOP, holding technical training, having quality controls, data
      collection, checking and statistics of food chemical contaminant monitoring.
      RESULTS: 14 categories of foods and 129 chemicals were cumulatively surveyed in
      16 provincial areas for ten years. A database with more than 1.05 million
      monitoring data was established. Monitoring results showed that food safety
      situation in China was generally stable and gradually good, but also problems of
      some food safety were found. Monitoring data had been used for alerts,
      supervision, risk assessment and standard setting of food safety. CONCLUSION: The
      monitoring for 10 years knew about the contamination levels and dynamic trend of
      contaminants in food, provided scientific data for the development of food safety
      policies and laws, and laid the foundation for national food contamination
      monitoring.

PMID- 22611924
TI  - [Effects of citreoviridin on the expression of MCP-1 and ILs induced by TNF-alpha
      in vein endothelial cells].
AB  - OBJECTIVE: To investigate the effects of citreoviridin (CIT) on the expression of
      MCP-1, IL-1beta, IL-6 and IL-8 induced by TNF-alpha in human umbilical vein
      endothelial cells (HUVECs). METHODS: HUVECs isolated from the umbilical cord of
      neonates within 1 hour after birth (informed with consent form) were cultured in
      DMEM/ F12 media. After 80% of HUVECs were confluent, the cells were divided into
      four groups and treated with CIT (2 micromol/L) and/or TNF-alpha (10 microg/L).
      The levels of MCP-1, IL-1beta, IL-6 and IL-8 in the supernatant of cell culture
      media were measured by ELISA, the activation of NF-kappaB in HUVECs was detected
      by immunofluorescence staining, and the expression of MCP-1 mRNA was determinated
      by RT-PCR assay. RESULT: The levels of MCP-1, IL-1beta, IL-6 and IL-8 in the
      supernatant and the expression of NF-kappaB P65 and MCP-1 mRNA of HUVECs were
      higher in TNF-alpha group and TNF-alpha + CIT group than those in the control
      group (P < 0.05), and those of TNF-alpha + CIT group was higher than TNF-alpha
      group (P < 0.05). CONCLUSION: The expression of NF-kappaB, MCP-1, IL-1beta, IL-6
      and IL-8 in HUVECs up-regulated by TNF-alpha was promoted by CIT.

PMID- 22611928
TI  - [Physical activity and bone mineral density in postmenopausal women].
AB  - OBJECTIVE: To test the association of total and physical activity (PA) intensity
      levels with bone mineral density (BMD) and bone mineral content (BMC) in
      postmenopausal women. METHODS: 315 postmenopausal women (50-70 y) were recruited
      for this cross-sectional study from community residents in Guangzhou, China. PA
      and related covariates including general characteristics and dietary intakes were
      assessed using a face-to-face interview. BMD and BMC were determined by a dual
      energy x-ray absorptiometry, at the whole body, lumbar spine (L1-AL4), total hip
      and its sub-sites. RESULTS: The participants were tertiled according to metabolic
      equivalent (MET) of PA. Analysis of covariance showed that greater PA tended to
      correlated to better BMD and BMC at various sites. Mean (S) BMDs at the whole
      body were (1.045 +/- 0.008), (1.043 +/- 0.008), (1.068 +/- 0.008) g/cm2 in the
      tertile I, II and III of total PA. BMD was significantly higher in the tertile
      III than those in the tertile I (P = 0. 049) and II (P = 0.028). No significant
      difference was observed at other sites. Mean BMC was significantly higher in the
      of highest total PA group than those in the other two groups at total femur,
      femoral neck, shaft femur and ward's triangle (P = 0. 004-0. 042). The
      association was differed by PA intensity levels. BMD tended to be increased with
      less light-intensity PA, more moderate-intensity PA and moderate vigorous
      intensity PA. CONCLUSION: Greater total PA and moderate-intensity PA, and
      moderate vigorous-intensity PA might improve bone mass in postmenopausal women.

PMID- 22611927
TI  - [Methodology of infant and young child feeding index for children aged 6-24
      months in China].
AB  - OBJECTIVE: To establish a infant and young child feeding index (ICFI) in China to
      comprehensive evaluate the feeding of children aged 6-24 months. METHODS: Based
      on the feed index concept defined by Ruel and Menon in 2002, and according to the
      feeding principle by WHO and Chinese dietary guidelines for children aged 0-6
      years, the feed index for infants and young children was built and the variables
      were scored. Then using WAZ, HAZ and WHZ, the correlation between ICFI and Z
      score for children in urban and rural of three provinces (Sichuan, Hebei and
      Heilongjiang) was evaluated. RESULTS: The ICFI was constituted by 7 parts:
      continued breast-eeding, bottle-feeding, dietary diversity for the past 24 h,
      frequency of feeding solids/semisolids for the past 24 h, food frequency for the
      past 7d, the supplementary time of the formula milk and other foods. The
      difference of ICFI score between urban and rural group was significant (P <
      0.05). In urban, the ICFI score of children aged 6-8 months was lower than that
      of children aged 9-24 months. In urban, the negatively correlation between ICFI
      and WAZ WHZ was significant (P < 0.05). In rural, the negatively correlation
      between ICFI and WHZ was significant (P < 0.05), while the positively correlation
      between ICFI and HAZ was significant (P < 0.05). CONCLUSION: ICFI is effective to
      evaluate the infant feeding in China.

PMID- 22611929
TI  - [Study on effects of eating behaviors intervention for 3-5 years old children in
      Beijing and Shanghai].
AB  - OBJECTIVE: To improve the unhealthy eating behaviors in 3-5 years old children
      and enrich the nutrition knowledge of their parents by the multi-channel health
      education intervention, and evaluate the effects of intervention. METHODS: By
      random multi-stage cluster sampling, 810 children (3-5 years old) and their
      parents were selected from Beijing and Shanghai respectively. The period of
      intervention was 6 months. Questionnaire surveys about children's eating behavior
      and the knowledge of their parents were conducted before and after the
      intervention. RESULTS: After the intervention, the proportion of partial eclipse
      and drinking beverage declined from 44.5% and 70.4% to 35.5% and 31.7%
      respectively. The proportion of having regular meal time, fixed dining place,
      eating by oneself, fix quantify diet and concentrating on food elevate from
      80.0%, 87.3%, 73.4%, 32.1% and 27.1% to 92.1%, 90.2%, 83.7%, 44.3% and 40.1%. The
      awareness about nutrition in parents increased and the attitude to the children's
      eating behaviors improved after the intervention. CONCLUSION: The intervention
      has some effects on the improvement of the children' s unhealthy eating behaviors
      and their parents' nutrition knowledge and attitude.

PMID- 22611930
TI  - [Study on change characters and correlations of iron, zinc and calcium in milk
      and blood of mother and infant at different stages].
AB  - OBJECTIVE: To assess the change characters of mineral status in breast milk and
      blood of lactating mothers and infants at different postpartum stages, and to
      analyze the clinic significance of these changes in breastfeeding. METHODS: 50
      mother-infant pairs at 6 weeks postpartum and 50 mother-infant pairs at 3 months
      postpartum were randomly selected, and the concentration of iron, zinc and
      calcium in milk and blood of mothers and infants were measured according to flame
      atomic absorption spectrometry. Compared the disparity of these minerals at
      different stages, and analyze the correlations of the ones among milk, blood of
      mothers and infants. RESULTS: the level of iron and zinc declined through
      lactation(Fe 0.102 mg/100 g vs 0.0605 mg/100 g, P < 0.05; Zn 0.257 mg/100 g vs
      0.171 mg/100 g, P < 0.05). The level of iron ion in blood of infants declined
      with increasing age (392.45 mg/L vs 356.80 mg/L, P < 0.05). The level of iron,
      zinc and calcium ion in maternal blood was not associated with these minerals of
      milk, and separately positively associated with these minerals in blood of infan
      (r = 0.591, 0.362 and 0.435, P = 0.000, 0.013 and 0.001). CONCLUSION: The mammary
      mineral transport is likely an active process, and not apparently associated with
      maternal mineral status. The decline of milk iron through lactation may be one of
      the reasons for high prevalence of breast-fed infants' physiologic anemia.
      Maternal mineral status during pregnancy may have an influence on the mineral
      levels of infants in early period.

PMID- 22611931
TI  - [Status of knowledge and behaviors about chronic diseases prevention for Chinese
      residents in 2008].
AB  - OBJECTIVE: To learn the status of knowledge and behaviors about chronic diseases
      prevention for Chinese residents, and to provide basis for developing health
      education strategy. METHODS: Using multi-stage stratified random cluster
      sampling, 79 542 residents aged 15-69 years old from 31 provinces (municipalities
      and autonomous regions) and Xinjiang Production and Construction Corps in
      Mainland China were investigated with the questionnaire of chronic diseases
      prevention. RESULTS: There were 78 429 valid questionnaires recovered. The
      effective questionnaire return rate reached 98.60%. For some questions such as
      how to face second hand smoking, diseases types caused by second hand smoking,
      milk daily intake, drink daily intake for adult and the correct cognition to
      weight control, the correct rates were all below 30%. There were only 3.87%
      respondents possessed knowledge and behaviors about chronic diseases prevention.
      The proportion possessed knowledge and behavior about chronic diseases prevention
      of the urban population was higher than that of the rural population. The
      proportion of respondents aged from 35 to 45 was higher than that of other
      respondents. The higher were educational levels, the higher was the proportion.
      These differences had all statistical significance (P < 0.01). CONCLUSION: The
      proportion possessed knowledge and behavior about chronic diseases prevention of
      respondents was low, especially to some specific prevention measurement such as
      how to control salt daily intake. In future, different health education
      strategies about chronic diseases prevention should be developed for different
      population.

PMID- 22611932
TI  - [Influence of short-term weight intervention on glycolipid metabolism of patients
      with type II diabetes].
AB  - OBJECTIVE: To explore how health management of short-term weight intervention
      affects glycolipid metabolism of patients with type II diabetes. METHODS:
      Overweight or obese type II diabetes mellitus patients were under weight
      intervention for 45 days with health management model and the epidemiologic
      method of self control. RESULTS: Compared with before intervention, the levels of
      both fasting blood-glucose (FBG) and blood-glucose 2 hours after meal, weight,
      BMI, waistline, hip circumference and upper arm circumference of the patients
      after intervention lowered significantly (P < 0.05), levels of serum TC, HDL-C,
      LDL-C increased obviously (P < 0.05), and TG levels did not change significantly.
      CONCLUSIONS: Due to the particularity of their blood lipid metabolism mentioned
      above, when carrying out health management of short-term weight intervention on
      patients with type II diabetes.

PMID- 22611933
TI  - [Determination of pesticide residues and microcystin in drinking water using on
      line SPE liquid chromatography-mass spectrometry].
AB  - OBJECTIVE: To develop a method based on on-line solid phase extraction followed
      liquid chromatography mass spectrometry for determination of 9 pesticides and
      microcystin-LR in drinking water. METHOD: Drinking water samples were
      concentrated by a HRP-SPE cartridge and separated on a HSS T3 column with a
      gradient mobile phase of acetonitrile and aqueous 0.1% formic acid, then analyzed
      by triple quadrupole mass spectrometry (TQ-MS) and time of flight mass
      spectrometry (TOF-MS), respectively. Mass acquisition was conducted under
      positive electrospray ionization mode. Quantification was performed by external
      standard calibration. RESULTS: The quantification limits (LOQs) of 10 target
      compounds were far below the limits set by the National Standards for Drinking
      Water Quality. The LOQs of TOF-MS was 0.01-0.40 microg/L and the LOQs of TQ-MS
      was 0.01-0.19 microg/L. Recoveries of 10 target compounds were 66.5%-130.3% with
      relative standard deviation between 0.8% and 14.5%. CONCLUSION: Due to its
      rapidness, simpleness, and high sensitivity, the method is suitable for the
      determination of pesticides and microcystin-LR in drinking water.

PMID- 22611934
TI  - [Analysis of 20 sulfonamides in sewage sludge by high performance liquid
      chromatography tandem mass spectrometry].
AB  - OBJECTIVE: To develop a comprehensive method for simultaneous analysis of 20
      sulfonamides in sewage sludge by liquid chromatography tandem mass spectrometry
      (LC-MS/MS). METHODS: Ultrasonic extraction and accelerated solvent extraction was
      compared with respect to the recovery of target drugs from sludge. Cleanup
      procedure was optimized during the test. The sludge samples were ultrasonicly
      extracted and purified by a mix mode anion-ion exchange solid-phase extraction,
      following determination using LC-MS/MS. 20 sulfonamides were separated by a C18
      column and analyzed under positive ion mode with multi-reaction monitoring.
      Isotopic internal standards calibration was used for quantification. RESULTS: The
      method quantification limits for 20 analytes were 0.25-10.0 microg/kg with
      overall recoveries of 50.1%-120.0%, and the relative standard deviations less
      than 30%. The method was finally used to analyze sulfonamides in sludge from
      sewage treatment plants in Beijing, and 3 target compounds (sulfadiazine,
      sulfapyridine and sulfamethoxazole) were detected at a concentration range of 2.1
      153.1 microg/kg. CONCLUSION: This method could be applied in simultaneous
      analysis of 20 sulfonamides in municipal sludge samples.

PMID- 22611935
TI  - [Hypermethylation and downregulation of tumor suppressor gene p16 in benzene
      poisoning].
AB  - OBJECTIVE: To investigate whether benzene negatively affects the expression of
      p16 through DNA methylation. METHODS: We carried out a case-control study in
      Chinese occupational benzene poisoning patients. Eleven cases of BP and 8
      controls who were matched for age (+/- 5 years), sex, working duration and job
      title with BP were recruited. Expression level was examined by quantitative real
      time PCR. Bisulfite-PCR pyrosequencing was used to quantitate the level of DNA
      methylation. RESULTS: The expression levels of p16 are down-regulated in BP
      patients compared to the control group (0.53 versus 2.06, P = 0.064). The average
      percentage of methylated cytosines of p16 was higher in BP group than in controls
      (12.4%, 11.3%, respectively, P > 0.05). p16 mRNA level decreased with increasing
      methylation (Pearson r = -0.64, P > 0.05). The fourth CpG site in p16 promoter is
      located within the consensus binding sequence for olfactory neuron-specific
      transcription factor. A significant negative correlation between mRNA level and
      the fourth CpG site was exhibited (Pearson r = - 0.88, P < 0.05). CONCLUSION: Our
      report demonstrated that mRNA expression of p16 is significantly downregulated in
      BP patients. Hypermethylation in promoter CpG islands is likely to contribute to
      the downregulation of p16. Further in-depth studies, utilizing large number of
      samples, are needed to fully understand the molecular mechanism involved in the
      tumor-suppressor gene inactivation in benzene-related diseases.

PMID- 22611936
TI  - [Association between genetic polymorphism of metabolizing enzymes and DNA
      repairing enzymes and the susceptibility of lung cancer in Henan population].
AB  - OBJECTIVE: To investigate the association between genetic polymorphism of
      metabolizing enzymes and DNA repairing enzymes and the susceptibility of
      pulmonary cancer in Henan population. METHODS: A case-control study of 209 lung
      cancer patients and 256 healthy control subjects was conducted in Henan
      population to investigate the role of CYP1A1-Msp1, CYP1A1-exon7, GSTM1, GSTT1,
      mEH-exon3, mEH-exon4 and XRCC1 in lung cancer. Genotyping was performed by using
      PCR based restriction fragment length polymorhphism techniques. RESULTS: The
      frequency of GSTM1-null, CYP1A1-exon7 mt/mt, mEH-exon3 mt/mt, XRCC1-194 Trp/Trp,
      XRCC1-280 His/His genotype in the lung cancer case group was significantly higher
      than that in control group (P < 0.05). The risk of lung cancer was higher in
      individuals carrying genotypes of GSTM1 (ORadj = 1.76, 95% CI 1.21-2.56, P =
      0.005), CYP1A1-exon7 Ile/val + val/val (ORadj = 1.65, 95% CI 1.16-2.39, P =
      0.009), mEH-exon3 wt/mt + mt/mt (ORadj = 1.77, 95% CI 1.18-2.64, P = 0.007),
      XRCC1-194 Arg/Trp + Trp/Trp (ORadj = 1.55, 95% CI 1.07-2.27, P = 0.016) and XRCC1
      280 His/His (ORadj = 2.21, 95% CI 1.05-4.52, P = 0.026) than those carrying
      genotypes of GSTM1 null, CYP1A1-exon7 Ile/Ile, mEH-exon3 wt/wt, XRCC1-194 Arg/Arg
      and XRCC1-280 Arg/ Arg + Arg/His; There was no significant difference for CYP1A1
      Msp1, GSTT1, mEH-exon4, XRCC1-399 genotype between the two groups (P > 0.05).
      CONCLUSION: The genetic polymorphisms of CYP1A1-exon7, GSTM1, mEH-exon3, XRCC1
      194 and XRCC1-280 might contribute to the risk of developing lung cancer in Henan
      population.

PMID- 22611937
TI  - [Effect of L-arabinose on glucose and lipid metabolism in type 2 diabetic rats].
AB  - OBJECTIVE: To investigate the effect of L-arabinose on glucose and Organ and
      islet in type 2 diabetic rats. METHODS: Male Wistar rats were fed high-sugar and
      high-fat diet after 8 weeks, then inject streptozotocin intraperitoneally
      according to 25 mg/kgbw dose to establish animal models of type 2 diabetes, and
      fed L-arabinose according to a low dose (50 mg/kgbw ), medium dose (150 mg/kgbw)
      and high dose (500 mg/kgbw) ,the animal be fed acarbose (20 mg/kgbw) as a
      positive control, the use of L-arabinose and acarbose were prepared in the
      dextrin (0.36 g/ml) and sucrose (0.04 g/ml) of the suspension, free to eat water.
      OGTT after 4 weeks, After animal death, rat liver, epididymal fat and cecum were
      weighed and calculate the ratio of organ weight. Results compared with model
      group, low, animals with L-arabinose-intervention those blood glucose response
      had a significant impact, 30 min, 60 min, 120 min blood glucose values and AUC
      were significantly lower than the model group (P < 0.05), of which medium dose is
      most significant (P < 0.01). L-arabinose intervention increased cecal weight and
      showed protective effect on beta-cell. CONCLUSION: L-arabinose long-term
      intervention can improve glucose tolerance in type 2 diabetic rats, this effect
      may be related to L-arabinose inhibition of digestive enzymes and the protective
      effect on beta-cell.

PMID- 22611938
TI  - [Effects of magnesium intake on expression of insulin receptor in type 2 diabetes
      rats].
AB  - OBJECTIVE: To investigate the effects of magnesium intake on expression of
      insulin receptor in type 2 diabetes rats. METHODS: The models of type 2 diabetes
      rats were established by feeding with high-fat-diet and injecting streptozotocin
      (STZ). Rats were randomly assigned to four groups. The high-fat-diets were
      administrated magnesium at a dose of 2000 (high magnesium group), 1000 (medium
      magnesium group) and 200 (low magnesium group). Model control group was only fed
      with high-fat-diet. Normal control group was fed with common diet. Rats ate
      freely for four weeks. Fasting blood glucose was detected by glucose oxidase
      method.. Insulin was detected by radio-immunity method. The expression levels of
      IR of pancreas and skeletal muscle were detected by immunohistochemistry method.
      RESULTS: The immunohistochemistry pictures were analyzed by Image-Pro Plus.
      Compared with model control group, the expression levels of IR of pancreas and
      skeletal muscle were 0.341 +/- 0.001 and 0.346 +/- 0.002, increased and fasting
      blood glucose decreased significantly in high magnesium group (P < 0.05 ).
      CONCLUSION: Magnesium intake may increase the expression levels of IR of pancreas
      and skeletal muscle, and decrease fasting blood glucose in type 2 diabetes rats.

PMID- 22611939
TI  - [Folic acid prevents Bcl-2 hypomethylation in rats with hyperhomocysteinemia].
AB  - OBJECTIVE: To investigate the effects of folic acid on Bcl-2 gene methylation
      status in rats with hyperhomocystinemia induced by ingestion of excess
      methionine. METHODS: 36 healthy 6-week-old wistar male rats, weighing (160 +/-
      10) g, after being fed adaptable for one week, were randomly divided into control
      group (n = 12), hyperhomocysteinemia group (n = 12), folic acid treatment group
      (n = 12). The control group was fed with AIN-93G diet. The hyperhomocysteinemia
      group was fed with high-methionion diet, consisting of AIN-93G diet plus 1.7%
      methionion. The folic acid treatment group was fed with high-methionion plus
      folic acid-rich diet, consisting of AIN-93G diet plus 1.7% methionion and 0.008%
      folic acid. After be maintained for 18 weeks on the previously described diets,
      the concentrations in the plasma Hcy and folic acid and Vit B12 were measured
      with the IMX assays. The thoracic aorta was harvested for immunohist Chemical
      analysis. The methylation status of Bcl-2 gene was determined by nest touch-down
      PCR combined MSP(methylation specific PCR). Real-time RT PCR was used to detect
      mRNA expression of arotic Bcl-2. RESULTS: The study showed the following: (a) A
      high methionine diet for 18 weeks is sufficient to induce hyperhom degree
      Cystinemia; Folic acid supplementation to the rats fed the high-methionine diet
      prevented an elevation homocysteine (Hcy) levels in the plasma (P < 0.01 ). (b)
      Compared with the control group, the Hhcy group had a elevating Bcl-2 expression
      by immunohistochemical analysis in aorta, along with Bcl-2 hypomethylation (P <
      0.05) and increased Bcl-2 mRNA expression (P < 0.05 ). (c) Most important, after
      folic acid supplementation, the lowering of Hcy levels was accompanied by a
      marked decreased Bcl-2 expression by immunohistochemical analysis and Bcl-2
      hypermethylation (P < 0.05) and reduced Bcl-2 mRNA expression (P < 0.05).
      CONCLUSIONS: Folic acid supplementation can prevents Bcl-2 hypomethylation in
      rats with hyperhomocysteinemia, resulting in a decreased Bcl-2 expression.

PMID- 22611940
TI  - [Simultaneous determination of bromate and perchlorate in vegetable by ion
      chromatography tandem mass spectrometry].
AB  - OBJECTIVE: To develop a method for simultaneous determination of bromate and
      perchiorate in vegetable using ion chromatography tandem mass spectrometry.
      METHODS: Target ions in vegetable matrix were extracted by water and purified
      using a GCB cartridge. With the hydrophilic Ion Pac AS19 column and linear
      gradient potassium hydroxide used as eluent, bromate and perchlorate were
      analyzed by a triple quadrupole mass spectrometer under negative electronspray
      ionization mode and multiple reaction monitoring (MRM). Internal standard
      calibration was used for quantification. RESULTS: Good linearity was achieved for
      bromate and perchlorate over the range of 0.1- 50 microg/L and 0.05-50 microg/L,
      respectively, with correlation coefficients R2 > 0.998. The quantification limits
      of the method were 2.5 microg/kg and 0.7 microg/kg for bromate and perchlorate,
      respectively. Mean recoveries of two target analytes (spiked at three
      concentration levels in 5 kinds of vegetables) ranged from 80.3% to 124%, with
      within-day precisions no more than 21.4% and intraday precisions no more than
      12.2%. CONCLUSION: This method could be applied in the simultaneous detection of
      bromate and perchlorate in vegetable.

PMID- 22611941
TI  - [Research on the isolation of denitrifying bacteria from domestic wastewater and
      its capability of removing nutrient salt from eutrophic water body].
AB  - OBJECTIVE: A kind of bacteria associated with highly denitrifying capability was
      isolated, and investigated about its growth and degradation characteristics.
      METHODS: By using an enrichment culture and plate dilution method, one strain of
      bacteria was isolated from domestic wastewater and their denitrifying capability
      on the river water received domestic wastewater was determined. RESULTS: The
      isolated bacteria strain had some nitrogen and phosphorous removal ability, its
      denitrifying intensity was 63.2%. The efficiencies of removing TN (total
      nitrogen) and TP (total phosphorus) (76.2% and 93.8%, respectively) were the
      highest when the consortium was added at the dosing amount of 100 mg/L after
      treatment for 10 days. CONCLUSIONS: One strain of denitrifying bacteria was
      successfully isolated from sewage sediments; its removal capacity of nitrogen and
      phosphorus from eutrophic water was good, which provided a basic biological
      method for nitrogen and phosphorus removal associated with eutrophic sewage
      treatment.

PMID- 22611942
TI  - [Simultaneous determination of six antibiotics in disinfection products by high
      performance liquid chromatography tandem mass spectrometry].
AB  - OBJECTIVE: To develop a method for determination of the Metronidazole,
      Chlortetracycline hydrochloride, Oxytetracycline dihydrate, Minocycline
      hydrochloride, Erythromycin and Tetracycline hydrochloride in disinfection
      products by high performance liquid chromatography tandem mass spectrometry(LC
      MS/MS). METHODS: Samples were extracted by methanol and filtered through 0.45
      microm PTFE membrane filter, then analyzed by LC-MS/MS using Waters Symmetry C18
      (2.1 mm x 150 mm, 3.5 microm) column in positive ion scan mode. The mobile phase
      was 5 mmol/L ammonium acetate, methanol and acetonitrile. RESULTS: The linear
      range was 0-2000 ng/ml and the correlation coefficients were more than 0.998, the
      average recoveries ranged from 74.7% to 114% with the relative standard
      deviations between 1.6%-20.2%. The method was successfully used to detect the
      content of antibiotics in 115 disinfection products. CONCLUSION: The method is
      simple, sensitive, selective and suitable for the analysis of residual content of
      antibiotics in cream formulations of disinfection products.

PMID- 22611943
TI  - [Determination of 47 organophosphorus pesticide residues in drinking water by
      membrane extraction-gas chromatography-PFPD].
AB  - OBJECTIVE: To establish a method for the rapid determination of organophosphorus
      pesticide residues in drinking water by membrane extraction-gas chromatography.
      METHODS: The pesticides were extracted from 1000 ml water sample with the
      activation of the C18 solid disk membrane. Then the extract was eluted by ethyl
      acetate, dehydrated by anhydrous sodium sulfate, nitrogen at least in 1 ml, set
      the volume to 1 ml. The volume was 2 microl for injection by gas chromatography.
      RESULTS: The spiked recoveries were between 81.8%-122.8%, the RSD were 2.67%-24%,
      the detection limits of different organophosphorus pesticides were 0.006-0.35
      microg/L and the LLOQ were 0.022-1.2 microg/L. CONCLUSION: The method is simple,
      rapid, sensitive, repeatable, reliable and suitable for determination of trace
      organophosphorus pesticide in water.

PMID- 22611944
TI  - [Comparison of different magnetic beads for adsorption of pathogenic bacteria].
AB  - OBJECTIVE: To establish a rapid enrichment method of pathogenic bacteria by
      comparing the adsorption capacity of the bare magnetic beads and immunomagnetic
      beads. METHODS: With the precipitation method, the Fe3O4 magnetic beads were
      coated with silica and modified with the amino, which could immobilize antibody
      by cross-linking reaction. The adsorption capacity of different magnetic beads
      for pathogenic bacteria were compared. RESULTS: The bare magnetic beads and
      Fe3O4/SiO2 immunomagnetic beads were prepared by chemical synthesis and chemical
      modification. There were significant differences in adsorption rates between
      immunomagnetic beads and magnetic beads (t = 7. 55, P < 0.05), the average
      adsorption rates were 96.62% and 80.89% respectively. Optimizing the washing
      condition, the adsorption rates of immunomagnetic beads for target and non-target
      bacteria were decreased from 97.03% to 93.67% and from 53.33% to 16.67%
      respectively. The adsorption rates of bare magnetic beads was reduced to 13.33%
      from 81%. No significant association was found in the adsorption rates of the
      immunomagnetic beads coating with single antibody and mixed antibody (P = 0.427).
      CONCLUSION: The target bacteria were specifically captured by the immunomagnetic
      beads coationg with single antibody and mixed antibody, and it could achieve good
      adsorption effect based on the enrichment iptimization.

PMID- 22611945
TI  - [Measurement of purines and uric acid simultaneous in meat with high performance
      liquid chromatographys].
AB  - OBJECTIVE: To determinate adenine, guanine, hypoxanthine, xanthine and uric acid
      simultaneously in meat, a reversed-phase high performance liquid chromatography
      (HPLC) was developed. METHODS: The meat were hydrolyzed with perchloric acid 10%
      (v/v) in boiling water for 60 mm. After the hydrolysate was adjusted to pH 4,
      centrifuge , and filtrated with a 0.45 mirom membrane, the supernatants were
      separated on an Agilent ZORBAX Eclipse XDB-C18 column (250 mm x 4.6 mm i.d., 5
      microm) at 25 degrees C with a mobile phase of 7 x 10(-3) mol/L KH2PO4-H3P04(pH
      4.0) ,a flow rate of 1.0 ml/ mm, and UV detection at 254 nm. RESULTS: Each
      component in the corresponding concentration range showed a good linear relation
      with its peak area, correlation coefficient r > 0.9999, recovery was 90.0%-107.
      5%, RSD was 1.7%-13.3%. In addition to containing four kinds of purines, there
      was quite amount of uric acid (about 133.7 -86.2 pug/g) in the mentioned meat.
      The ratio of uric acid to total purine and uric acid was about 7%. The content of
      total purine in chicken was (1759.3 +/- 64.6) microg/g higher than in rabbit,
      mutton, pork and beef (1440-1000 microg/g). CONCLUSION: The validated method is
      simple, rapid, accurate and reliable to the determination of purines and uric
      acid in meat.

PMID- 22611946
TI  - [Synergistic effect of diabetes family history and abnormal waist-to-hip ratio on
      the incidence of type 2 diabetes].
AB  - OBJECTIVE: To explore the synergistic effect between diabetes family history and
      abnormal waist-to-hip ratio (WHR) on the incidence of type 2 diabetes. METHODS:
      Population-based case-control study was conducted. The interaction between
      diabetes family history and abnormal WHR was analysed by an additive model.
      RESULTS: After adjusting confounding factors by multiple logistic regression
      analysis, the synergy index was 5.63, the attributable risk was 1.49, and the
      attributable interaction percent was 52.9%. CONCLUSION: There was a synergistic
      effect between diabetes family history and abnormal WHR on the incidence of type
      2 diabetes.

PMID- 22611947
TI  - [An investigation on vitamin D levels in peripheral blood in rheumatoid
      arthritis].
AB  - OBJECTIVE: To study the association between vitamin D levels and RA. METHODS:
      Seventy-two postmenopausal female patients with RA (group RA) and fifty-eight
      healthy volunteers (group control) were included in this study. 25-hydroxyvitamin
      D3 (25-(OH) D3) levels were determined by ELISA method and disease activity of RA
      was assessed according to the Disease Activity Score in 28 joints (DAS28). The
      difference of 25-(OH) D3 levels between two groups and the relationship between
      25-(OH) D3 levels and DAS28 were assessed. RESULTS: 25-(OH) D3 levels in
      peripheral blood in group RA were significantly lower than that in group control
      (P < 0.05), and 25-(OH)D3 levels were negatively correlated with DAS28.
      CONCLUSION: Vitamin D may have double actions of prevention, treatment and
      evaluation during the diagnosis and treatment process with RA disease.

PMID- 22611948
TI  - Misconceptions about routine colposcopy.
AB  - Colposcopy is practised in two ways: (1) to assess women with abnormal screening
      findings and/or clinically suspicious cervix (called referral colposcopy), and
      (2) as part of a routine gynaecological examination (referred to as routine
      colposcopy). There are several misconceptions about routine colposcopy probably
      reflecting the lack of experience in using routine colposcopy. Misconceptions
      include: routine colposcopy is screening colposcopy, it is time-consuming,
      expensive, a waste of time, and the training and maintaining of colposcopic
      expertise is probably not sufficient in this setting. Routine colposcopy,
      however, is not a screening tool, it is not screening colposcopy, but capable of
      identifying cervical precursors and cancer, and thereby reducing the false rates
      of cervical cancer screening (mainly cytology). Unlike referral colposcopy,
      routine colposcopy is an inexpensive and rapid procedure conducted as a part of a
      pelvic examination and has no, or minimal, discomfort that certainly does not
      exceed that of smear taking, neither is it associated with any psychological
      burden. Routine colposcopy allows gynaecologists to be convincingly sure in their
      findings; ensure women having normal epithelium; evaluate abnormalities in
      details (without biopsy) and counsel patients immediately to alleviate the
      psychological effects and prepare them for a possible abnormal smear; as well as
      help make a diagnosis of obscure lesions.

PMID- 22611949
TI  - Repeat conisation or HPV test? What should be done if histology of the primary
      conisation requires a second conisation?
AB  - OBJECTIVE: In our retrospective study we focused on the sensitivity of HPV DNA
      testing towards reducing the number of repeat (re)conisations. Is the second HPV
      test (pre repeat conisation) an appropriate method to reduce the number of
      interventions in histologically positive cases? STUDY: 438 cervical conisations-
      loop electrosurgical excision procedure (LEEP)--were performed between March 2008
      and August 2010 at our Gynaecology Department. Samples for high-risk HPV testing
      (Genoid, Hungary) were taken from the surface of the cervix and from the cervical
      canal before the LEEP procedure, and histopathological examinations were
      performed. Margin positivity was the indication for re-conisation (re-LEEP).
      RESULTS: 119 (27.2%) out of 438 cases were re-conisations. In cases of
      histologically proven residual dysplasia (29 of 119) high-risk HPV infection was
      also detected by HPV testing. In 90 cases of 119 residual dysplasia was not seen
      by histological examination. In this high-risk group HPV infection had not been
      detected in 77 cases (85.5%) by the time the second HPV test was performed. HPV
      tests for high-risk types were positive only in 13 of 90 (14.5%) without residual
      dysplasia. Furthermore the same HPV type was detected only in three cases taken
      before the first and second conisation procedure. CONCLUSION: Pre re-conisation
      HPV testing might be useful in reducing the number of re-conisations where the
      high-risk HPV test is either negative or does not confirm the previously proven
      HPV type.

PMID- 22611950
TI  - Clinical significance of serum growth-regulated oncogene alpha (GROalpha) in
      patients with gynecological cancer.
AB  - PURPOSE OF INVESTIGATION: To assess the clinical relevance of serum growth
      regulated oncogene alpha (GROalpha) levels in gynecological cancer, we
      investigated its concentration in distinguishing patients with cervical cancer,
      endometrial cancer, ovarian cancer, benign ovarian tumor and control. METHODS:
      Preoperative serum GROalpha levels were measured in women with cervical cancer
      (n=46), endometrial cancer (n=39), ovarian cancer (n=124), benign ovarian tumors
      (n=52), and normal controls (n=38) using an enzyme-linked immunosorbent assay.
      RESULTS: Statistical analyses showed that the serum GROalpha concentration was
      significantly elevated in the cervical cancer, endometrial cancer and ovarian
      cancer patients compared with controls. Using GROalpha levels, the receiver
      operating characteristic (ROC) of cervical cancer (AUC approximately 0.775),
      endometrial cancer (AUC approximately 0.799), ovarian cancer (AUC approximately
      0.749) and benign ovarian tumors (AUC approximately 0.568) vs. controls were
      identified. CONCLUSION: Our findings suggest that serum GROalpha measurement as a
      molecular marker might contribute to detection and diagnosis of gynecological
      cancer.

PMID- 22611951
TI  - Correlation between preoperative endometrial sampling and final endometrial
      cancer histology.
AB  - OBJECTIVE: We conducted a study to evaluate the correlation between pre-operative
      endometrial sampling to the final endometrial cancer histology, in particular the
      non-endometrioid subtypes. METHODS: This involved 191 hysterectomy specimens of
      patients undergoing treatment at the Pan-Birmingham Gynaecological Regional
      Cancer Centre (BGCC) over a two-year period (2006-2007). RESULTS: The majority of
      the patients in this study were found to have endometrioid histology subtype
      (140/191, 73%). However, the non-endometrioid histologic subtypes were well
      presented in our population (51/191, 27%). We found good correlation for
      endometriod histology subtype (78%) and certain types of the non-endometrioid
      cell types (carcinosarcoma 90%, uterine papillary serous carcinoma 67%, clear
      cell carcinoma 67%) but poor in sarcomas (40%). Our results also demonstrated
      that both pre-operative endometrial sampling methods (curettage and pipelle
      biopsy) were reliable in identifying endometrioid and non-endometrioid cancer
      cell types, with sensitivities of 96.5% and 86.5%, respectively. CONCLUSION: We
      concluded that preoperative endometrial sampling had good overall histological
      correlation to hysterectomised corpus specimen. This is especially so for the
      endometrioid and certain subtypes of the non-endometrioid endometrial cancer
      cells.

PMID- 22611952
TI  - The association between polymorphisms of the RAD51-G135C, XRCC2-Arg188His and
      XRCC3-Thr241Met genes and clinico-pathologic features in breast cancer in Poland.
AB  - BACKGROUND: XRCC2 and XRCC3 genes are structurally and functionally related to
      RAD51 which plays an important role in homologous recombination, the process
      frequently involved in cancer transformation. MATERIAL AND METHODS: In the
      present work the distribution of genotypes and frequency of alleles of the RAD51
      G135C polymorphism, XRCC2 Arg 188His and XRCC3 Thr241Met polymorphism in 790
      cases of breast cancer were investigated. The control group consisted of 798
      cancer-free blood donors (age +/- 5 years) who were sex and ethnicity-matched.
      The polymorphisms were determined by PCR-RFLP methods. We also correlated
      genotypes with the clinical characteristics of breast cancer patients. RESULTS:
      Our results obtained for the 135G>C polymorphism of the RAD51 gene indicated that
      both the C/C genotype and the C allele are strongly associated with breast
      cancer. The Arg/His genotype of XRCC2 (OR = 2.16, 95% CI = 1.48-3.16) and Thr/Met
      of XRCC3 increased the risk of type I breast cancer occurrence (OR = 2.33, 95% CI
      = 1.60-3.41). We did not find any association with the RAD51, XRCC2/3 gene
      polymorphism and estrogen and progesterone receptor status. CONCLUSION: The
      results support the hypothesis that the polymorphism of RAD51 and XRCC2/3 gene
      may be associated with the incidence of sporadic breast cancer in Polish women.

PMID- 22611953
TI  - Sentinel node disection in the treatment of early stages of vulvar cancer.
AB  - OBJECTIVES: To assess the results of sentinel lymph node (SLN) detection in the
      initial stages of vulvar cancer and the recurrences that may appear. STUDY
      DESIGN: 76 patients with vulvar carcinoma, Stage I and II. Between 2000 and 2010,
      identification of the SLN was performed with a perilesional injection of Tc99m
      and vital dye. Ninety sentinel lymph nodes were found. They were removed
      separately, and lymphadenectomy was performed depending on the involved areas.
      Vulvar tumour was also removed. RESULTS: 76 patients were included in the study;
      20 (22.22%) out of 90 SLNs presented metastases and 70 (77.77%) did not. There
      were no false negatives, and the sensitivity and negative predictive value
      reached 100%. Thirty-six months after treatment, one patient presented recurrence
      with a negative SLN, and two with positive SLNs. CONCLUSION: Biopsy of the SLN is
      a reasonable alternative to lymphadenectomy in patients with vulvar cancer Stage
      I and II.

PMID- 22611954
TI  - Minimally invasive mastectomy: minimal incisions for better aesthetic quality of
      breast reconstruction.
AB  - BACKGROUND: Women with a family history of breast cancer who develop this disease
      are confronted with important situations regarding the increased risk for
      development of a second cancer in the contralateral breast. Prophylactic
      contralateral mastectomy (PCM) reduces by approximately 95% the risk for
      contralateral breast cancer. In spite of an increase in indications for PCM, the
      technical difficulties are many regarding the accomplishment of these procedures.
      The aim of this study is to describe the technique of mastectomy with
      preservation of the nipple-areola complex and a small incision, reducing surgical
      difficulties and complications attributed to this technique, thus allowing better
      aesthetic results in breast reconstruction. METHODS: Forty-six patients with
      indications for PCM (28 bilateral) were submitted to minimally invasive
      mastectomy from March 2005 to November 2007. A small incision in the superior
      pole of the areola, sufficient to pass a liposuction 4 mm cannula is made. With
      the help of this cannula, detachment of the skin from the gland tissue is
      performed. Then a 3.5 to 4.5-cm long incision in the inframammary fold is made.
      Glandular detachment is completed using cautery in the subglandular portion and
      scissors in the upper breast portion cutting the restraints left by the cannula.
      The mammary gland tissue is removed through this incision. RESULTS: Seventy-four
      breasts were operated on. The resected breast mass ranged from 285 g to 475 g.
      All 43 patients were reconstructed with prostheses. There was no necrosis of the
      nipple-areola complex or of the skin. CONCLUSIONS: This technique is an option
      for cases of patients with indications for PCM.

PMID- 22611955
TI  - Prognostic importance of selected molecular immunohistochemical markers and DNA
      ploidy in endometrial cancer.
AB  - The aim of the study was the analysis of the new molecular genetic immunomarkers
      (p53, c-erbB-2, Ki 67, bcl-2) hormonal receptors (ER, PR) and ploidy disturbances
      and their relation to the most important prognostic factors for endometrial
      cancer. The study group consisted of 135 endometrial cancer patients. Biopsies of
      the tumours obtained at operations were routinely histopathologically examined.
      Subsequenly, the immunohistochemical tumour markers were determined. The same
      biopsies were examined by microdissection and flow cytometric ploidy analysis and
      karyotyping. The findings were compared with the most important prognostic
      factors for endometrial cancer, mainly with clinical stage of the disease and
      grade. RESULTS: High expression of p53, Ki 67, c-erbB-2 and low rate of
      progesterone receptors was found in the prognostically unfavourable group (G 3).
      Aneuploidy was found in 72% in the group of poorly differentiated endometrial
      cancers (G 3) in contrast to 27% in the group of G1 and G2 tumours, but this
      difference was not statistically significant. CONCLUSIONS: Identification of p53,
      Ki 67, c-erbB-2, PR and determination of DNA ploidy is a useful tool to specify a
      group of prognostically unfavourable patients.

PMID- 22611956
TI  - Evaluation of E6 and E7 mRNA expression in HPV DNA positive breast cancer.
AB  - Several studies have suggested a possible role for HPV in the pathogenesis of the
      breast cancer. We investigated the presence of the HPV DNA in breast cancers and
      non malignant disease breast tissues by the use of a standard HPV detection
      method (INNO-Lipa HPV), in order to detect HPV DNA in metastatic nodes, to
      investigate a possible cervical HPV co-infection, and to evaluate the E6/E7 mRNA
      expression in HPV DNA positive breast cancer tissues. The rate of HPV infection
      was significantly higher in the cancer group than in controls (9/31 vs. 0/12, p =
      0.04). One out of eight metastatic axillary nodes was positive for HPV infection;
      2/3 of the positive HPV breast cancer patients were co-infected at the cervical
      site. The role of the virus in breast oncogenesis is still unclear, since our
      analysis failed in demonstrating the expression of viral E6 and E7 in positive
      HPV positive breast tumor tissues.

PMID- 22611957
TI  - Comparison of risk of malignancy indices; RMI 1-4 in borderline ovarian tumor.
AB  - PURPOSE: The aim of this study was to evaluate prognostic values of the risk of
      malignancy index (RMI)/1-4 in patients with borderline ovarian tumors (BOTs).
      METHODS: The study consisted of 50 patients with BOT diagnosed and treated
      between 2005-2010 and 50 patients with benign adnexal massses between 2009-2010
      as a control comparison group in the retropsective study. Preoperative serum
      CA125, U score, tumor size (S), and menopausal status were recorded. The RMI 1-3
      was calculated according to the formula; UxMxCA125 and RMI4 formulation was;
      UxMxCA125xS. S equaled 1 for tumor size <7 cm and was 2 when size a 7 cm. The RMI
      1-4 indices were calculated for all patients together with the sensitivity,
      specificity, positive predictive value (PPV), negative predictive value (NPV),
      and diagnostic accuracy (DA). The performances of RMI indices were evaluated by
      McNemar's test and determined the best score cutoff value by the receiver
      operating characteristic (ROC) curve. RESULTS: The mean age, median value of
      CA125, ultrasound score, menopausal status, median values of RMI 1-4 of BOTs were
      statistically higher than benign adnexal masses. The sensitivity of RMI 1-4 was
      26, 36, 62, and 60% at cutoff 200 level, respectively. The areas under curve of
      RMI 1-4 were found to be 0.676, 0.665, 0.668 and 0.734, respectively. DA of RMI 1
      4 was found to be 56, 59, 50, and 71, respectively. When RMI 1-4 indices were
      compared with each other RMI 4 was the best RMI for BOTs. CONCLUSION: RMI 4 was
      the best predictive RMI for preoperative discrimination of BOT at a cutoff level
      of 200.

PMID- 22611958
TI  - Laparoscopic management of unexpected borderline ovarian tumors in women of
      reproductive age.
AB  - PURPOSE OF INVESTIGATION: The aim of this study was to review the clinical
      features of women with unexpected borderline ovarian tumours. METHODS: Between
      October 1992 and December 2010, 1332 out of 4016 laparoscopies were performed for
      adnexal masses in women of reproductive age and 1838 cysts were removed. When
      ultrasonographic findings did not meet the criteria for low risk malignancy,
      tumour markers, colour Doppler and MRI/CT were applied. At laparoscopy any solid
      component or papilla was sent for rapid frozen section. RESULTS: Borderline
      ovarian tumours were found in eight (0.6%) out of 1332 patients, two of which
      were bilateral. The mean age was 28.75 +/- 9.27 years and the mean diameter of
      the cysts was 5.1 +/- 1.7 cm. In two cases unexpected malignancy was discovered
      during the diagnostic and in six cases during the operative phase of the
      intervention. CONCLUSION(S): Risk of failure to diagnose cancer could be
      minimised with careful patient selection preoperatively. Adequate training on
      laparoscopic oncology is the necessary prerequisite for a safe laparoscopic
      approach.

PMID- 22611959
TI  - Expression of survivin and VEGF-C in breast cancer tissue and its relation to
      lymphatic metastasis.
AB  - PURPOSE: To study the expression of survivin and VEGF-C in breast cancer tissue
      and its relation to lymphatic metastasis. METHODS: The expression level of
      survivin and VEGF-C in breast cancer tissue is determined by immunohistochemistry
      and reverse transcriptase polymerase chain reaction (Rt-PCR). RESULTS: Among the
      60 breast cancer tissues, the percentage of positive expression of survivin or
      VEGF-C was 85.0% and 78.3%, respectively. The expression rate of VEGF-C was 84.3%
      (43/51), 44.4% (4/9) in the survivin positive and negative expression group,
      respectively. Linear correlation analysis showed a correlation coefficient of
      survivin and VEGF-C in breast cancer was 0.80 (p = 0.035), which indicates a
      positive correlation between the two biomarkers. CONCLUSIONS: Survivin and VEGF-C
      are highly expressed in breast cancer tissues with a positive correlation. The
      regulation of survivin expression can cause excessive expression of VEGF-C,
      leading to the generation of breast cancer lymphangiogenesis, thus causing
      lymphatic metastasis of breast cancer.

PMID- 22611960
TI  - Accuracy of physician and nurse practitioner colposcopy to effect improved
      surveillance of cervical cancer.
AB  - PURPOSE: To compare physician and nurse practitioner accuracy in recognizing
      cervical dysplasia during colposcopy. MATERIALS AND METHODS: A retrospective
      review was performed of cervical excisional biopsies from 2007 to 2009 performed
      by gynecologists and nurse practitioners in the same patient population. Cervical
      cone biopsy and loop electrosurgical excision procedure (LEEP) pathology were
      used as a gold standard compared to the previous colposcopy biopsies. RESULTS:
      Four hundred fifty-five patients qualified for the study. Patients were
      stratified according to age: under 30 years, 30-39, and 40 and above. For
      physicians, 77% of high-grade colposcopy biopsy results agreed with high-grade
      pathology on cone biopsy or LEEP. This was statistically similar to nurse
      practitioner results (p = 0.12). Likewise, there was no significant difference
      between physician and nurse practitioner accuracy within the various patient age
      strata. CONCLUSION: Colposcopy biopsy results compared to cone biopsy or LEEP
      results were statistically similar between gynecologists and nurse practitioners.

PMID- 22611961
TI  - Impact of sampling origin on molecular detection of high-risk human
      papillomavirus and oncogene expression.
AB  - PURPOSE OF INVESTIGATION: The recognition of high-risk human papillomavirus (HR
      HPV) as an etiological agent of cervical cancer has increased the importance of
      testing for HPV, and this might contribute to better risk stratification.
      METHODS: Eighty-eight randomly selected cervical cancer specimens including
      biopsies and their respective smears were used in this study. Control scrapings
      were obtained from ten healthy women. The presence of HPV16 and HPV18 was
      investigated using the technique of polymerase chain reaction (PCR) with the
      specific primers for the L1 region, while mRNA expression of HPV16 E6-E7 was
      evaluated by a reverse transcription PCR method (RT-PCR). RESULTS: The positivity
      for the viral genotype was influenced by the quantity of amplified DNA used. In
      tumor biopsies the higher positivity for HPV16 (54.5%) and HPV18 (15.9%) was
      obtained using 687.4 ng of DNA. At smears level solely 31.8% of HPV16 was
      detected using an average DNA quantity of about 157.2 ng. The revelation of HPV
      types depends on clinicopathologic data; HPV16 was detected more in advanced
      stages of squamous carcinoma (SC) samples (20% stage I, 62% Stage II and 80%
      stage III), while HPV18 and double infection were found exclusively at advanced
      stages of SC and in adenocarcinoma (AC), respectively (60%, 40% stage III SC and
      80%, 20% Stage II A and C). The prevalence of HPV16 E6-E7 transcripts was
      evaluated at tumor biopsy with frequencies of 50%. CONCLUSION: Our data provide
      prospective evidence that HPV16/18L1 revelation at biopsy toward pathological
      types is efficient and correlates well with oncogenic transcript findings. Subtle
      changes in viral oncogene dynamics highlight the presence of other regulating
      proteins serving as additional biomarkers.

PMID- 22611962
TI  - The impact of presurgical magnetic resonance in early breast cancer: an
      observational study.
AB  - The aim of this study was to evaluate the impact of presurgical breast magnetic
      resonance imaging (MRI) on the surgical management of selected patients with
      early-stage breast cancer who were candidates for BCT. The sample was built up
      according to the EUSOMA (European Society of Breast Cancer Specialists)
      recommendations enrolling women with unifocal unilateral early-stage breast
      carcinoma diagnosed by mammography, ultrasound (US) examination and in some cases
      also by histological analysis; all were scheduled for wider local excision. All
      eligible patients underwent presurgical breast MRI and findings were classified
      according to the BI-RADS system. In the presence of additional foci classified as
      BI-RADS 3-4, a targeted second-look US study was performed. If second-look US
      confirmed the presence of foci, needle biopsy was performed. Possible changes in
      the therapeutic approach resulting from preoperative MRI findings were decided
      upon by a multidisciplinary team. Outcome of histological examination of the
      surgical specimen and particularly analysis of tumor infiltration of the
      resection margins was the standard for determining the appropriateness of
      surgical strategy. A total of 123 patients underwent presurgical breast MRI.
      Additional foci were detected in 41.6% of patients, a greater local extension of
      the index lesion in 6.4%, whereas MRI confirmed local staging established by
      conventional imaging in 52%. However, 13.8% of additional foci were not confirmed
      by second-look and needle biopsy. More extensive surgery as a result of MRI
      findings was performed in 34.2%. This decision proved to be appropriate in 29.3%
      thus resulting in an over-treatment rate of 4.9%. Presurgical breast MRI resulted
      in confirmation of planned surgical strategy in 65.8% with an appropriateness
      rate of 54.5%. Surgical resection margins were positive for malignancy in 11.3%
      and repeated surgery was therefore required. Therapeutic strategy established on
      the basis of MRI was appropriate in 83.8% of cases. This study confirms the
      utility of MRI in presurgical workup of selected breast cancer patients. The
      results obtained suggest the importance of a sensitive tool such as MRI in the
      local staging of breast cancer before treatment planning.

PMID- 22611963
TI  - Radical abdominal trachelectomy is a safe and fertility preserving option for
      women with early stage cervical cancer.
AB  - PURPOSE OF INVESTIGATION: To present the surgical, oncological and obstetrical
      outcomes gained from patients who underwent radical abdominal trachelectomy (RAT)
      in Zeynep Kamil Women and Children Diseases Education and Research Hospital and
      radical Yeditepe University Hospital. METHODS: A total of eight RATs were
      performed between 2003-2010. Data were obtained from medical and pathological
      records of the patients. RESULTS: The mean age of the patients was 27.37 +/- 6.39
      years. The mean follow-up time of the patients was 33.62 +/- 27.47 months. Three
      (37.5%) patients had a tumor size smaller than 2 cm, and five (62.5%) patients
      had a tumor size larger than 2 cm. Seven (87.5%) patients had stage IB1 and one
      (12.5%) patient had stage IIA tumor. Three (37.5%) patients had late
      postoperative complications: uterotubal abscess, severe lymphedema and
      lymphocyst. There were no recurrences. Three patients became pregnant which
      resulted in two live births and one abortus. The spontaneous pregnancy rate was
      50%. CONCLUSION: We think that RAT is a reliable surgical option for a patient
      with early stage cervical cancer who wants to preserve fertility.

PMID- 22611964
TI  - Distribution of human papillomavirus types in Turkish women.
AB  - PURPOSE OF INVESTIGATION: Since oncogenic types of human papillomavirus (HPV) are
      associated with a higher risk of cervical cancer and certain types can be
      controlled by a vaccine, a study has been performed to determine the HPV genotype
      distribution among Turkish women. METHODS: The study included patients with
      abnormal cytology or in the follow-up for cervical intraepithelial neoplasia
      between 2002 and 2009 at Hacettepe University Hospital. The results of 1797
      consecutive cervical samples were analyzed retrospectively. INNO-LiPA HPV
      genotyping, HPV-Typing and Seeplex HPV 18-plex genotyping tests were used to
      determine the types of HPV. RESULTS: HPV was detected in 404 (22.4%) of 1797
      samples studied. HPV DNA was identified in 194 cases by using HPV-Typing test but
      the specific genotype was not available. The most frequent genotype was HPV 16
      which was observed in 103 cases (49.0%). CONCLUSION: HPV 16 was the most common
      genotype observed among Turkish women with abnormal cytology. It suggests that
      HPV vaccination may be useful for prevention of cervical cancer in this
      population.

PMID- 22611965
TI  - Do high levels of CA 19-9 in women with mature cystic teratomas of the ovary
      warrant further evaluation?
AB  - PURPOSE: To evaluate the serum levels of tumor markers (particularly CA 19-9) in
      patients with ovarian mature cystic teratomas (MCT) with respect to age, size,
      bilaterality, menopause, presence of adhesions, complications and the
      postoperative levels. METHODS: We evaluated clinical characteristics and tumor
      markers of 157 patients with MCT of the ovary operated at our clinic. RESULTS:
      CA19-9 was the only tumor marker with a mean serum level (46.95 +/- 101.11 U/ml)
      above the cut-off value and the elevated rate was 33.1%. Tumor size, presence of
      adhesions and CA 125 levels were significantly higher in patients with elevated
      CA 19-9. Bilaterality rate was 10.8%. The most common complication was torsion
      (6.4%). CONCLUSION: We suggest that elevated levels of CA 19-9 may be expected in
      MCTs of the ovary and that they will probably be decreased postoperatively.
      Therefore, postponing evaluation of other possible sources of CA 19-9 elevation
      in asymptomatic and young patients is more common sense.

PMID- 22611967
TI  - Peritonitis due to iatrogenic colpotomy after large loop excision of the
      transformation zone (LLETZ) in a patient with cervical intraepithelial neoplasia
      III: our experience of a rare case with review of the literature.
AB  - A case of peritonitis as an unusual complication of LLETZ (large loop excision of
      the transformation zone) for the treatment of CIN III associated with
      unrecognized iatrogenic posterior colpotomy is presented. After the procedure,
      the patient developed fever 38.3 degrees C and diffused severe pelvic pain. The
      contributing factors, prevention and management of this complication are
      discussed. Also, the complications of cold knife cervical conization and LLETZ
      procedure are reviewed.

PMID- 22611966
TI  - The role of surgery in patients with advanced gynaecological cancers
      participating in phase I clinical trials.
AB  - OBJECTIVE: While gynaecological cancer patients who participate in Phase I
      clinical trials are not routinely considered for elective surgery because of a
      short life expectancy, this should not be overlooked in carefully selected
      responding patients. METHODS/RESULTS: We describe two cases of patients with
      different gynaecological cancers, who received treatment within separate phase I
      trials, and who then proceeded to surgical resection of their cancers, resulting
      in complete remission. CONCLUSION: Surgery, when feasible, should be taken into
      consideration as a potential management option, even when patients are receiving
      treatment within a phase I trial.

PMID- 22611968
TI  - Bilateral androblastoma (Sertoli-stromal cell tumor) of the ovary: a rare cause
      of virilization in a teenager.
AB  - A case of a 17-year-old patient diagnosed with bilateral androblastoma of the
      ovary is presented. The patient was admitted because of secondary amenorrhea,
      hirsutism and acne. After clinical, ultrasonographic and hormonal examinations an
      androgen-producing ovarian tumor was suspected and consequently laparotomy with
      right ovarian tumor excision and left ovary exploration was carried out. During
      surgery the right ovarian tumor was excised and exploration of the left ovary
      revealed an ovarian tumor with a diameter of 10 mm, which was then also excised.
      The pathologic diagnosis was a bilateral androblastoma of the ovary measuring 40
      mm x 30 mm x 20 mm in the right ovary and 10 mm in diameter in the left ovary. We
      concluded that androblastomas, in spite of their low incidence, are a possibility
      that should always be considered in women of all ages presenting with signs of
      virilization.

PMID- 22611969
TI  - Malignant lymphoma of the vagina successfully treated with rituximab, adryamicin,
      cyclophosphamide, vincristine sulfate, and prednisolone.
AB  - PURPOSE: Primary malignant lymphoma of the vagina is extremely rare. The most
      common histologic subtype is diffuse large B-cell lymphoma (DLBCL). We report a
      case of vaginal DLBCL successfully treated with chemotherapy consisting of
      rituximab, adryamicin, cyclophosphamide, vincristine sulfate, and prednisolone (R
      CHOP), followed by pelvic irradiation. CASE: A 44-year-old Japanese woman was
      admitted complaining of atypical genital bleeding and puruloid vaginal discharge.
      Gynecological examination showed an ulceration of the vaginal wall and a hard
      mass the size of a goose egg beneath the left vaginal wall, which had infiltrated
      to the left pelvic wall. The pathological diagnosis based on a punch biopsy taken
      from the vaginal tumor was non-Hodgkin's lymphoma. Based on immunohistochemical
      study, the tumor was subclassified as activated B-cell type DLBCL. The patient
      was diagnosed with Ann Arbor Stage IEA DLBCL and Stage III vaginal cancer,
      according to the International Federation of Gynecologists and Obstetricians
      (FIGO) classification system. She was successfully treated by six courses of R
      CHOP, followed by radiation therapy. The patient is well without evidence of
      disease 13 months following the initial treatment. CONCLUSION: Little attention
      has been paid to the use of rituximab in addition to conventional chemotherapy
      and the importance of clinical and morphological subgrouping of DLBCL arising in
      the vagina. The present case indicates that the effects of rituximab on the
      prognosis of vaginal DLBCL must be evaluated, and that clinical use of
      immunophenotypic subgrouping should be considered for vaginal DLBCL.

PMID- 22611970
TI  - Malignant mixed Mullerian tumor of the fallopian tube: a case report.
AB  - Malignant mixed Mullerian tumor (MMMT) of the female genital tract is uncommon
      and extremely rare in the Fallopian tube. We describe a case of primary MMMT of
      the Fallopian tube with carcinomatous and heterologous mesenchymal components in
      a 60-year-old woman. The patient underwent total abdominal hysterectomy,
      bilateral salpingo-oophorectomy, infracolic omentectomy, pelvic and paraaortic
      lymph node dissection, and resection of intrapelvic metastases. The tumor formed
      a large polypoid mass within the right Fallopian tube and had penetrated the wall
      to the paraovarian space. Microscopic examination revealed two components of
      poorly differentiated adenocarcinoma and high-grade sarcoma with chondromatous
      differentiation. The patient received six courses of adjuvant chemotherapy with
      ifomide and cisplatin and is currently in remission. Although MMMT in the
      Fallopian tube shows poor prognosis, primary cytoreductive surgery with platinum
      based combination chemotherapy may improve survival.

PMID- 22611971
TI  - Pseudomyxoma peritonei--case report.
AB  - The syndrome pseudomyxoma peritonei is rare, present in only 2/10,000
      laparotomies. We report the case of a 58-year-old woman with a primary tumor of
      the appendix, and secondary involvement of other structures and organs of the
      abdominal cavity. In our case, we performed maximal surgical reduction of the
      tumor, with remaining implants on diaphragmatic domes and liver, as we did not
      have technical conditions to safely perform prolonged surgery which would have
      included a surgical procedure on the liver and administration of intraoperative
      chemotherapy. The patient underwent six series of parenteral chemotherapy, but
      refused the second-look surgery. Even though our patient did not receive
      intraperitoneal chemotherapy, maximal surgical tumor reduction, and refused
      second-look surgery, she is still alive and without any major complaints two
      years after the surgery.

PMID- 22611972
TI  - Borderline clear cell adenofibroma of the ovary associated with ovarian
      endometriosis: a case report.
AB  - Clear cell tumours of the ovary are relatively uncommon. Most of them are clear
      cell carcinomas. Benign and borderline clear cell tumours are extremely rare and
      almost always fibromatous. We report a case of a 34-year-old woman. Ultrasound
      and computed tomography showed a right ovarian mass 8 cm in diameter. The patient
      underwent right salpingo-oophorectomy. Microscopic examination revealed glands
      and cysts different in size and shape within an abundant stromal component
      without evidence of stromal invasion. Many cysts and glands were lined by a
      single layer of flattened, cuboidal or hobnail cells with mild to moderate
      cytologic atypia and prominent nucleoli. Psammomatous calcifications were
      occasionally indentified. Features of endometriosis were also present adjacent to
      the tumour. Lesional cells were positive for Ker 7 and CA125. Staining for p53
      was focally positive. Based on the above characteristic morphologic and
      immunohistochemical findings a diagnosis of borderline clear cell adenofibroma
      was made. The patient was free of recurrence four years after surgery.

PMID- 22611973
TI  - Tumor of the mesosalpinx: case report of a female adnexal tumor of probable
      Wolffian origin.
AB  - We report a rare case of a 45-year-old woman who underwent laparoscopy for a
      right mesosalpinx mass. Pathologic examination showed a female adnexal tumor of
      probable Wolffian origin (FATWO). FATWO represents a rare gynecologic tumor and
      its clinical and pathological features are often ignored. Immunohistochemistry
      plays the most part in the diagnosis of FATWO. Through this report, we aimed to
      call attention to this disease in order to better understand the correct
      treatment and surgical possibilities, and to evaluate and perform the prognosis
      properly.

PMID- 22611974
TI  - Malignant fibrous histiocytoma of the ovary: a case report.
AB  - Malignant fibrous histiocytoma (MFH) is the most common soft-tissue sarcoma of
      late adult life occurring predominantly in the extremities and the
      retroperitoneum. MFH of the ovary is very rare, with only six cases previously
      reported. A 67-year-old woman with a right pelvic tumor highly suspicious of
      ovarian carcinoma was submitted to exploratory laparotomy. Total abdominal
      hysterectomy, bilateral salpingo-oophorectomy, total omentectomy, pelvic and
      paraaortic lymphadenectomy with right hemicolectomy along with permanent
      cutaneous ileostomy were performed. Since a storiform-pleomorphic type of MHF was
      diagnosed from histopathological and immunohistochemical findings, chemotherapy
      was proposed as the postoperative treatment. Despite extensive surgery with
      negative surgical margins, the patient had recurrence of the tumor within four
      months, and was submitted to secondary surgery. A combination of chemo- and
      radiotherapy was performed postoperatively, but the patient developed respiratory
      problems and died one year later from the primary diagnosis.

PMID- 22611975
TI  - [The symptoms, signs and deviations revealed during clinical and laboratory
      studies].
AB  - The standardized indicators of mortality of population in Russia exceed the
      corresponding indicators in Europe in three groups of pathology: external causes
      (4.7 times), cardiovascular diseases (3.1 times), symptoms, signs and deviations
      (3.2 times). In 2010, the morbidity of children aged 0-14 years and 15-17 years
      included 2.2% of symptoms, among adult population 0.3% in totumn; in 2007-2.6% in
      children and 0.4% in adults; in various territories in children 6% (Stavropolsky
      kray Nenetsky natsionalny okrug), 11% (Voroniejskaya oblast) and even 14%
      (Nijegorodskaya oblast). The symptoms, signs and deviations are to be taken into
      account and to be monitored because they can be first signals about disease in
      process of formation and final diagnosis is yet to be done. According to the data
      of international study "The global ageing an adult health" the role of symptoms
      as a cause of turning to medical care will only to increase paralleling the
      ageing of population.

PMID- 22611976
TI  - [The morbidity of population on the territories of the Sibirsky federal okrug].
AB  - The comparative analysis of morbidity of population of the Sibirsky federal okrug
      was implemented on the territories with presence/absence of the regional
      diagnostic center The sampling of eleven statistical materials was used. It is
      established that higher level of the diagnostics using special examination
      techniques in the diagnostic centers permits to increase the detect of pathology
      (oncologic included) in population and to assess adequately the need in important
      curative rehabilitating technologies.

PMID- 22611977
TI  - [The characteristics of medical demographic situation in Kalujskaya oblast].
AB  - The study found out the last decade dynamics in size, birthrate, mortality and
      natural increase/decrease of population depending on residence, age structure and
      gender The assessment of trends in development of medical demographic process in
      Kalujsky region is given.

PMID- 22611978
TI  - [The medical social aspects of primary disability in the population of able
      bodied age].
AB  - The article represents the main results of comparative analysis of dynamics and
      causes of primary disability among population of able-bodied age of Stavropolsky
      Kray and the Republic of Ingrushetia. The authors focus their attention namely on
      primary disability as a variation of higher risk of development of preventable
      disability. The presented data can be applied in decision making concerning the
      activities decreasing the level of primary disability on the regional level.

PMID- 22611979
TI  - [The rate and dynamics of prevalence of diseases of digestive system in north
      Caucasus federal okrug and Stavropolsky kray].
AB  - The article presents the results of analysis of digestive system morbidity during
      last decade among adult population of Stavropolsky kray as compared with North
      Caucasus federal okrug and Russia in general. The analysis according classes of
      diseases established that in the structure ofgeneral morbidity according the
      appealability data first place is for diseases of respiratory organs, second
      place is for diseases of circulatory system, third place is for diseases of
      urogenital system, fourth place is for diseases of musculoskeletal system, fifth
      place is for traumas, intoxications and other aftermath of external causes, sixth
      place is for diseases of digestive system and also pregnancy, delivery and
      puerperal period In Stavropolsky kray, gastritis and duodenitis are registered
      much more infrequently as compared with corresponding morbidity increase among
      adult population of Russia from 2001 to 2010.

PMID- 22611980
TI  - [The characteristics of epidemiology of acute exogenous intoxications].
AB  - The article pays attention to the actuality of issue of steady increase of
      numbers of acute chemical intoxications. The data is presented concerning the
      characteristics of epidemiology of acute chemical intoxications. The need to
      develop and enhance the specialized toxicological service is emphasized

PMID- 22611981
TI  - [The medical social aspects of thermic trauma among children of Tyumen].
AB  - The analysis of clinical statistical data concerning the thermic trauma among
      1950 children revealed that boys less frequently than girls got burned. The
      children aged 1-3 years made the most part of hospitalized children. Depending on
      the season the most numbers of burns are registered in summer and autumn and on
      Mondays and Fridays. The major factors impacting the lethality among children
      with burns are established.

PMID- 22611982
TI  - [The principles of strategic development of public health in modern conditions].
AB  - The results of analysis of the concept of strategic development of public health
      is presented concerning prerequisites, priorities, principles, purposes, targets
      and main parameters of the development of health sector: The conceptual
      characteristics are analyzed concerning the structural alterations in public
      health system, i.e., the structural transformations of managerial and production
      factors of industry.

PMID- 22611983
TI  - [The analysis and forecast of the demographic situation tendencies in the
      Republic of Udmurtiya].
AB  - The unfavorable demographic situation tendencies in the Republic of Udmurtiya are
      characterized by the decrease of population size and incidentally the regressive
      type of age structure is supported. The evolution of demographic processes
      (natality, mortality, life expectancy) affected the age gender structure of
      population of the republic. The reproduction of population and generations
      replacement decelerated in the region with low population density

PMID- 22611984
TI  - [On the issue of enhancement of public health normative legal base of
      Voronejskaya oblast].
AB  - The data is discussed concerning the public health normative legal base of in
      Voronejskaya oblast as related to the processes sector development following the
      public policy and current legislation. It is emphasized that the adoption of
      normative legal acts and their implementation permitted not only to legitimate
      and define concretely the activities of all executive authorities in public
      health and ambulatory polyclinic institutions but also to achieve factual
      positive results in decreasing morbidity of managed and feral nidal infection on
      the territory of Voronejskaya oblast.

PMID- 22611985
TI  - [The organization of quality control of medical care on the territory of Orenburg
      oblast].
AB  - The article characterizes the functioning of the model of quality control of
      medical care of population in Orenburg oblast. The model comprises five levels of
      control: head of department, institution deputy head doctor institution quality
      control council, oblast public health ministry, territorial Roszdravnadzor body.
      The summing up is made concerning the implementation of standard" of medical care
      provision in oblast and municipal medical institutions. The results of work with
      citizen appeals concerning medical care quality enhancement and medical care
      accessibility.

PMID- 22611986
TI  - [The organization of prevention of tuberculosis among medical university
      students].
AB  - The article deals with the analysis of 94 cases of tuberculosis among students of
      Krasnoyarsk state medical university in 1987-2010. The characteristics of disease
      structure and the outcomes of treatment are established The importance of
      mandatoty annual fluorography of students as a group with higher risk of
      tuberculosis infection is proved The tuberculin sensitivity and tuberculosis
      mycobacteria contamination of students of curative and pediatric faculties are
      examined. It is demonstrated that teaching in medical university is to be
      considered as a risk factor of primary tuberculosis infection with consequent
      development of disease. The proposal was made to organize a specific prevention
      (BCG revaccination) for medical universities students especially during the
      period of epidemiologic troubles.

PMID- 22611987
TI  - [On the routing of patients with suspicion of and at the detection of malignant
      neoplasm in the health institutions as exemplified in Tchelyabinsk oblast].
AB  - The routing of patients plays a key role in early detection of oncologic
      diseases. The clear conception of this technique still is not adequately formed
      in many regions. In Tchelyabinsk oblast the developed scheme of routing of
      patients in case of suspicion on malignant neoplasm is an integral part of
      organizational complex of preventive activities. From 2005, this approach
      resulted in the increase of detection rate of tumors of I-II stages and in the
      decrease of indicators of identified primary neglected processes one-year and
      lethality.

PMID- 22611988
TI  - [The characteristics of functioning of hospice in the conditions of megapolis].
AB  - The article deals with the analysis of volume and structure of specific care
      exemplified by the field service of hospice of Nijny Novgorod and compared with
      specialized hospital department. The priority nosology and patients age
      categories are established as included into the care services of hospice field
      team.

PMID- 22611989
TI  - [The formation of social professional skills of students with limited
      possibilities].
AB  - The education of children and adolescents with limited possibilities is a system
      of economic, public, legal and individual personal measures supporting the
      optimal conditions to overcome this defect up to a degree of participation in
      public life on par with other citizen. In the Nijny Novgorod academic boarding
      school for the disabled the organization of activities forming the social
      professional skills are differentiated on terms and targets of education. The
      students of first course need the optimization of communication, enhancement of
      self-consciousness, formation of educational information perception, reasoning,
      involuntary memory voluntary logical memory attention, will, educational general
      intellectual expertise. The students of second course need more attention to
      making and optimization of various types of activity, activation of labor
      activity, forming of labor attitudes, communicative skills and enhancement of
      emotional and motivational sphere. The students of third course need to develop
      the skills of self-reliant work, motoric activity, dexterity labor skills,
      working discipline skills, rational attitude to group work, professional
      knowledge.

PMID- 22611990
TI  - [The ethical and legal aspects of professional activities of obstetrician
      gynecologist].
AB  - The article demonstrates that both highly developed bioethical consciousness and
      legal awareness and high level of bioethical and legal culture among obstetrician
      gynecologists are important factors of enhancement of medical care quality. This
      postulate is discussed on the example of issues related to the induced abortion.
      The approaches to this issues applied in various countries are considered.

PMID- 22611991
TI  - [The experience of application of sociological techniques to the patients of
      oncologic dispensary].
AB  - The issues accumulated in national out-patient care of oncologic patients demand
      a permanent assessment of the organization and effectiveness of this sector of
      medical care. The opinions of patients of Moscow oncologic dispensary No2 were
      analyzed to evaluate the actual condition of oncologic care. The questionnaire
      was developed to organize a survey of 535 oncological patients.

PMID- 22611992
TI  - [S. S. Andreyevsky a scientist and reformer of medical work in Russia].
AB  - The article deals with the activities of S. S. Andreyevsky--a heroic researcher
      of anthrax, known public health organizer and public figure. He played an
      important role in the development of Russian medical education.

PMID- 22611993
TI  - [A. L. Polenov--a prominent traumatologist and surgeon (to the 140th
      anniversary)].
AB  - The article presents the course of life and creative development of Andrey
      Lvovitch Polenov--a prominent Russian traumatologist and neurosurgeon, talented
      public health organizer public figure, pedagogue, academician of USSR AMS.
      honored scholar of the Russian Federation, USSR State Prize laureate.

PMID- 22611994
TI  - [The traditional obstetrics, puerperal rites and child nursing among Vainakhs].
AB  - Already in the beginning of XX century the traditional healing among Vainakhs
      consisted ofsynthesis of rational and religious magic methods, especially in
      obstetrics and healing of children. Some of these methods survived in time and
      even nowadays keep their medical hygienic significance. Nevertheless, a lot in
      traditional healing of Vainakhs, the rite side in particular has today only a
      historical value.

PMID- 22611995
TI  - [The work of Moscow communities of Sisters of Charity in own medical
      institutions].
AB  - The article analyses the medical activities of Moscow communities of Sisters of
      Charity in curative and educational institutions organized by the communities
      themselves. The social ministration of communities on the territory of Moscow is
      considered.

PMID- 22611996
TI  - [The training of Zemstvo low-grade medical workers in Middle Volga Gubernia].
AB  - The article deals with the input of zemstvo self-management into establishment
      and development of secondary professional medical education in the Middle Volga
      region in second half of XIX-early XX centuries. The activities of zenmstvo is
      discussed concerning the organization and support of the infrastructure of
      feldsher schools, midwifes schools, the admission rules, the requirements to
      feldsher school graduates being the zemstvo scholarship grant holders. The
      activity of feldsher schools is reflected concerning the advanced training of low
      grade medical workers.

PMID- 22611997
TI  - [The state of obstetrics in the national republics of North Caucasus during the
      first half of XX century].
AB  - In Caucasus, during the first half of XX century the organization of obstetric
      gynecological care of women accompanied by significant problems to be resolved in
      the conditions of burning deficiency of material and manpower resources. In the
      early 1950s the functioning of the system of obstetrics in the North Caucasus
      region needed more intensive organizational efforts and highest possible
      involvement of medical science achievements.

PMID- 22611998
TI  - Intraperitoneal lidocaine for decreasing intra-operative pain during postpartum
      tubal resection in Srinagarind Hospital.
AB  - OBJECTIVE: To evaluate the effectiveness and determine the minimal dosage of
      intraperitoneal lidocaine for pain relief during postpartum tubal resection in
      Srinagarind Hospital. MATERIAL AND METHOD: Sixty postpartum women, undergoing
      postpartum tubal resection performed by residents at the Department of obstetrics
      and gynecologic, were included in this randomized, double-blinded, placebo
      controlled study. They were randomly assigned to one of three groups. They all
      received 20 ml solution intraperitoneally. Group one received it as isotonic
      normal saline; group 2 received it with 100 mg of lidocaine; and group 3 received
      it with 200 mg of lidocaine. The intra-operative and post-operative pain was
      measured by using a numerical rating score (NRS, from 0-10). RESULTS: The mean of
      intra-operative NRS in the lidocaine groups (100 and 200 mg) were significantly
      lower than the isotonic normal saline group (3.40, 3.50 vs. 6.55, p-value 0.019
      and 0.024). No significant difference was found in the intra-operative NRS
      between 100 and 200 mg lidocaine (NRS 3.40 vs. 3.50, respectively, mean
      difference 95% CI -2.41 to 2.21). There was no significant difference in the
      immediate post-operative pain among these three groups (p-value 0.613).
      CONCLUSION: Intraperitoneal lidocaine instillation provides effective intra
      operative pain relief in postpartum tubal resection under local anesthesia. 100
      mg of lidocaine is effective in pain relief This technique was not effective for
      relief of immediate post-operative pain.

PMID- 22611999
TI  - The efficacy of rapid biophysical profile in predicting poor pregnancy outcomes
      in suspected intrauterine growth restriction fetuses: preliminary study.
AB  - OBJECTIVE: To determine the efficacy of the rapid biophysical profile (rBPP),
      which includes sound-provoked fetal movement detected by ultrasonography, and
      amniotic fluid index for antepartum fetal well-being assessment in suspected
      intrauterine growth restriction (IUGR) fetuses. MATERIAL AND METHOD: One hundred
      seven tests of rBPP were antenatally performed in 30 IUGR fetuses who attended
      the ANC unit at Maharaj Nakorn Chiang Mai Hospital between October 2009 and July
      2010. Pregnancy outcomes were prospectively recorded for subsequent analysis. The
      accuracy of rBPP was based on poor outcomes including fetal distress, low Apgar
      score, admission to the neonatal intensive care unit, and perinatal death.
      RESULTS: In 107 tests, the incidences of negative, equivocal, and positive rBPP
      were 88.8%, 10.3%, and 0.9%, respectively. There was one adverse pregnancy
      outcome of intrapartum fetal distress. The rBPP had a sensitivity of 100.0%, a
      specificity of 89.7%, a positive predictive value of 25%, and a negative
      predictive value of 100.0%. CONCLUSION: The rBPP may probably be an effective
      predictor of poor pregnancy outcome in IUGR fetuses. With its high specificity
      and rapidity, the rBPP may be used as a back-up test to confirm fetal well-being
      in pregnancies complicated by IUGR at the antenatal care clinic.

PMID- 22612000
TI  - Validate of clinical risk index for osteoporosis in Thai women at Phramongkutklao
      Hospital.
AB  - BACKGROUND: Osteoporosis is a common problem found in elderly people and the cost
      of treatment with its complications is much higher than the cost of diagnosis and
      prevention. However diagnosis of osteoporosis is hindered by an unavailability of
      dual energy x-ray absorptiometry (DXA). Many clinical risk index-scoring systems
      were developed to help prediction of osteoporosis such as Khon Kaen Osteoporosis
      Study (KKOS). The KKOS is one among those scoring systems based on the Thai
      population database. The objectives of the present study were to validate KKOS
      for prediction of osteoporosis in Thai women at Gynecologic Clinic of
      Phramongkutklao Hospital and to study the prevalence of women with osteoporosis
      diagnosed with KKOS. MATERIAL AND METHOD: Four hundred forty six Thai women, aged
      40 years or more attending the Gynecologic Clinic of Phramongkutklao Hospital,
      and had Bone mineral density (BMD) result were enrolled in the present study. The
      results of BMD were measured at the lumbar spine and femoral neck by DXA and
      KKOS. The score was evaluated and compared. RESULTS: Sensitivity and specificity
      of KKOS for prediction of osteoporosis were 48.6% and 68.1%, respectively.
      Prevalence of osteoporosis using KKOS was 23% while 32% were diagnosed with DXA.
      CONCLUSION: KKOS had low sensitivity and specificity for diagnosed osteoporosis
      in Thai women at Gynecologic Clinic of Phramongkutklao Hospital.

PMID- 22612001
TI  - Delay in pulmonary tuberculosis suspicion and isolation among hospitalized
      patients: Songklanagarind Hospital perspective.
AB  - OBJECTIVE: To study the factors influencing delayed pulmonary tuberculosis
      suspicion and isolation among hospitalized patients in Songklanagarind Hospital.
      MATERIAL AND METHOD: A prospective study examining the microbiologically
      confirmed pulmonary tuberculosis patients who were admitted in the hospital. The
      data collected included demographic data, HIV status, initial symptoms, and chest
      radiographs. RESULTS: Sixty inpatients were identified. Forty-five percent and
      30% of patients were admitted. There was delay in suspicion of pulmonary
      tuberculosis and delay in isolation in 18 (30%) and 24 (40%) patients,
      respectively. There was no statistical significance among delayed and non-delayed
      groups of pulmonary tuberculosis suspicion and isolation. CONCLUSION: The
      pulmonary tuberculosis suspicion and isolation should concern patients for whom
      TB is an etiologic implication.

PMID- 22612002
TI  - Skin manifestation of Thai HIV infected patients in HAART era.
AB  - BACKGROUND: Skin and mucocutaneous disease changed its spectrum after Highly
      Active Antiretroviral Therapy (HAART) had been introduced. Previous publication
      showed opportunistic infections (OIs) related skin disease was a major
      presentation in pre-HAART era, whereas non-infected skin disease became emerging
      in HAART era. There is no report describing skin disease in HAART era among Thai
      HIV-infected patients. OBJECTIVE: To describe the prevalence of skin and
      mucocutaneous disease in Thai HIV-infected patients after using HAART MATERIAL
      AND METHOD: A cross-sectional retrospective study analyzed skin diseases of 237
      HIV-infected patients who were currently on HAART who attended the out-patient
      skin clinic at Bamrasnaradura Infectious Diseases Institute between September 1,
      and October 31, 2010. There were 312 lesions. The skin diseases were diagnosed by
      dermatologists and grouped into four groups as infectious skin disease, non
      infectious inflammatory skin disease, tumor and miscellaneous group. Percentage
      was calculated in each of skin disease prevalence. RESULTS: The results showed
      155 (65%) were men, and mean (SD) of age was 41 (8.8). Median (IQR) of CD4 count
      was 330 (178, 527) cell/mm3. The regimens of HAART in the population were 79% for
      NNRTI based, 20% for PI based, and 1% for tripled NRTI. The time between initial
      HAART and date of diagnosis of most patients (52%) was more than three years. Non
      infected skin disease (61%) was the most common skin disorder prevalence,
      followed by infectious disease (31%), tumor (0.96%), miscellaneous (6.09),
      respectively. The most common skin disease was eczema (21%). Four subjects
      developed drug eruption, all from Efavirenz. Atypical presentation specifically
      to HIV patients as chronic hypertrophic erosive herpes genitalis (one of IRIS)
      was found in four patients (20% of all HSV infectious prevalence). CONCLUSION:
      Non-infectious inflammatory skin disease is the most common skin prevalence in
      HIV-infected patients after receiving HAART Eczema was the most diagnosed skin
      disease. There were skin diseases related to immune restoration after using HAART
      and from HAART itself but in low prevalence.

PMID- 22612003
TI  - Tenckhoff catheter malfunction corrected by gastric channel-cleaning brush
      without fluoroscopy.
AB  - OBJECTIVE: To review the modified gastric channel-cleaning brush without
      fluoroscopy technique, which is easier, faster and safer than the original
      technique for correcting catheter malfunction in Nongkhai hospital. MATERIAL AND
      METHOD: Clinical records of CAPD patients with catheter malfunction in our
      facility between November 1, 2009 and April 30, 2011 were reviewed. RESULTS: The
      present study included 34 patients and 36 episodes of Tenckhoff catheter
      malfunction. Mean age was 58.26 years, male to female ratio 14:20. Causes of ESRD
      include 22 diabetes mellitus, five hypertension, four renal calculi, one
      nonsteroidal anti-inflammatory drugs used, and two unknown etiology. Mean time
      from Tenckhoff catheter placement to develop catheter malfunction was 2.47
      months. Using the brush technique, 25 episodes were successfully corrected
      without any complications. Ten cases were corrected by surgical correction, of
      which seven were successful, and three were shifted to HD. By the way, one
      patient chose supportive treatment. CONCLUSION: The gastric channel-cleaning
      brush without fluoroscopy technique should be considered for correcting Tenckhoff
      catheter malfunction to reduce the rate of catheter removal and keep the patients
      longer in CAPD therapy since it is effective and safe.

PMID- 22612004
TI  - Thai Registry in Acute Coronary Syndrome (TRACS)--an extension of Thai Acute
      Coronary Syndrome registry (TACS) group: lower in-hospital but still high
      mortality at one-year.
AB  - BACKGROUND: The Thai Registry of Acute Coronary Syndrome (TRACS) registry was
      conducted five years after the first Thai Acute Coronary Syndrome (ACS) registry.
      OBJECTIVE: To describe demographics, management practices, and in-hospital
      outcomes of current Thai ACS patients and to seek for any significant changes in
      this registry from the earlier first Thai ACS registry. MATERIAL AND METHOD: The
      TRACS is a multi-centers, prospective, nation-wide registration with 39
      participating medical centers. Web-based data entry was used and the data were
      centrally managed and analyzed. RESULTS: Between October 007 and December 2008,
      2,007 patients were enrolled. Fifty-five percent had ST elevation myocardial
      infarction (STEMI), 33% had non-ST-elevation myocardial infarction (NSTEMI), and
      12% had unstable angina (UA). Overall prevalence of diabetes was 50.7%. The STEMI
      group was younger predominantly male, with less diabetes than NSTEMI. At
      presentation, lower percent of cardiogenic shock (7.9%) and cardiac arrest (2.8%)
      were noted. Sixty seven percent of the STEMI received reperfusion therapy.
      Thrombolysis was given in 42.6% and primary percutaneous coronary intervention
      (PCI) was performed in 24.7% of all STEMl patients. Median door-to-needle and
      door-to-balloon time were 65 and 127 minutes. The median time-to-treatment was
      285 min in the thrombolysis group and 324 min in the primary PCI group. Regarding
      NSTE-ACS, coronary angiography was performed in 38.4% and about one-fourth
      received revascularization either by PCI or bypass surgery during index
      admission. In-hospital mortality was 5.3% for STEMI, 5.1% for NSTEMI, and 1.7%
      for UA. When following the patients up to 12 months, the mortality was 14.1%,
      25.0%, and 13.8% respectively. CONCLUSION: The TRACS registry showed differences
      in demographic, management practices and in-hospital outcomes of the Thai ACS
      patients. Although mortality rate in this registry decreased significantly as
      compared to the first Thai ACS registry, the results had to be interpreted with
      caution because of the difference in characteristics and severity of the enrolled
      patients. At 12-month follow-up, the mortality rate was significantly higher in
      NSTEMI than STEMI or UA patients. Practice management should be considered
      particularly for the invasive strategy for these groups of patients.

PMID- 22612005
TI  - The effect of introducing inpatient mandatory generic drug substitution at
      Ramathobodi Hospital.
AB  - BACKGROUND: Generic substitution is a mechanism for reducing drug expenditure in
      many healthcare settings. Ramathibodi, a teaching hospital, has introduced
      mandatory generic drug substitution (228 items) for health schemes in inpatient
      service since September 1, 2009. OBJECTIVE: Explore prescribing patterns in
      overall and by patients' health schemes between Thai fiscal year 2009 and 2010,
      and estimate possible saving if this policy was extended to the outpatient
      service. MATERIAL AND METHOD: Prescribing data and registered populations between
      October 1, 2008 and September 30, 2010 were retrieved from the database and
      analyzed. RESULT: Original and generic expenditure rose 8.42 and 8.61%from 2009
      to 2010 respectively. Among 228 mandatory items, more original was switched to
      generic drugs, both in terms of value (6.5 to 7.2%) and in terms of volume (32.5
      to 33.8%). Some inpatients, mainly civil servants and self-pay patients,
      requested the original from the outpatient service where the mandatory
      substitution was not applied. If the policy were extended through all services,
      the government would save approximately 306.5 million Baht (US$ 10.1 million) per
      year However the hospital would reduce its profit by 53.1 million Baht (US$ 1.7
      million). CONCLUSION: After the policy was launched, more original mandatory
      drugs were switched to generic. To gain more saving, the policy may be expanded
      to outpatient service, and/or mandatory drug list should be reviewed
      periodically.

PMID- 22612006
TI  - Axial radiography of the normal distal femur for assessment of rotational
      alignment in Thai.
AB  - BACKGROUND: It is crucial to recognize and understand anatomical features of the
      distal femoral condyles especially for orthopedists that take care of the elderly
      patient with leg deformity. OBJECTIVE: Evaluate the rotational alignment of the
      distal femur by using axial radiographic technique. MATERIAL AND METHOD: Thirty
      six normal volunteers (72 knees) were enrolled in the present study. Mean age was
      39.47 years (range 20 to 57). Axes for rotational alignment of distal femur were
      outlined including posterior condylar (PC), anteroposterior (AP), anatomical
      epicondylar line (AEpi), and then angle between each pair of the axes were
      measured in the medial side including anteroposterior/posterior condylar (AP-PC)
      angle, anteroposterior/anatomical epicondylar (AP-AEpi) angle, and anatomical
      epicondylar/posterior condylar (AEpi-PC) angle. Gender and side were compared to
      each other Pearson correlation was calculated between age and all angles.
      RESULTS: Average AP-PC angle was 95.75 +/- 1.79 degrees. Average AEpi-PC angle
      was 6.77 +/- 1.97 degrees. Average AP-AEpi angle was 89.81 +/- 1.86 degrees.
      Results showed no statistically significant difference between side, gender and
      age. Intraobserver ICC were 0.6 to 0.92 and interobserver ICC were 0.68 to 0.87.
      CONCLUSION: The axial radiographic technique is reliable. The results of the
      present study are comparable with a previous study using the computerized
      tomography (CT) technique.

PMID- 22612007
TI  - The comparison between limited open carpal tunnel release using direct vision and
      tunneling technique and standard open carpal tunnel release: a randomized
      controlled trial study.
AB  - OBJECTIVE: To compare the operative outcome of carpal tunnel release between
      limited open carpal tunnel release using direct vision and tunneling technique
      (group A) with standard open carpal tunnel release (group B). MATERIAL AND
      METHOD: Twenty-eight patients were enrolled in the present study. A single blind
      randomized control trial study was conducted to compare the postoperative results
      between group A and B. The study parameters were Levine's symptom severity and
      functional score, grip and pinch strength, and average two-point discrimination.
      RESULTS: The postoperative results between two groups were comparable with no
      statistical significance. Only grip strength at three months follow up was
      significantly greater in group A than in group B. CONCLUSION: The limited open
      carpal tunnel release in the present study is effective comparable to the
      standard open carpal tunnel release. The others advantage of this technique are
      better cosmesis and improvement in grip strength at the three months
      postoperative period.

PMID- 22612008
TI  - The efficiency of the patient care team on 3-day protocol for early ambulation
      after MIS-TKA.
AB  - OBJECTIVE: To evaluate the efficiency of the patient care team on the 3-day
      protocol for early ambulation after minimally invasive surgery-total knee
      arthroplasty (MIS-TKA) MATERIAL AND METHOD: A consecutive series of 120 episodes
      of patient's admission for MIS-TKA in 103 patients, who were taken care of by a
      single patient care team, was included in the present study. A uniform multimodal
      pain management and a 3-day rehabilitation protocol were applied. Patient's
      demographic data, co-morbidities, pre- and postoperative pain, and patient's
      voluntary early ambulation following the 3-day protocol were evaluated. Patients
      who accomplished the 3-day protocol were defined as having progress in
      postoperative ambulation, ability to do basic activities of daily living (ADL)
      and able to comfortably walk on postoperative day 3 (POD 3). RESULTS: Patient's
      mean age was 67.5 years and 68% (70/103) of patients had medical co-morbidities.
      After surgery, serial mean pain scores from six hours to the day of discharge in
      the studied group were < 3. The 3-day protocol had an overall success rate of 89%
      (107/120) regardless of medical co-morbidities. However 32% of cases that had
      accomplished this protocol extended hospital stay due to non-medical reasons.
      Among 13 patients who were unable to accomplish the 3-day protocol, higher rate
      was found in patients who had > 1 medical co-morbidities. Comparing between
      unsuccessful and successful groups, there was a significantly increasing rate of
      unsuccessful protocol in patients who had > 1 medical comorbidities (69.2% vs.
      31.8%; p, < 0.05). There was no complication or readmission related to the early
      discharge program. CONCLUSION: The result of 3-day protocol handled by the
      patient care team for MIS-TKA was highly efficient without complications related
      to early ambulation. However, this early ambulation protocol may not be
      appropriate for patients who have multiple medical co-morbidities. Besides the
      role of the patient care team, the efficiency of postoperative ambulation
      protocol was additionally relied on surgeon's experience in the surgical
      technique and effective multimodal postoperative pain control.

PMID- 22612009
TI  - Comparison of age-based and height-based formula for tracheal tube size in
      cardiac children.
AB  - OBJECTIVE: To compare the effectiveness of age-based formula (ABF) and height
      based formula (HBF) for pediatric cardiac patients, including patients with
      failure to thrive (FTT). MATERIAL AND METHOD: In a retrospective study of 260
      cardiac patients that included those with failure to thrive, aged 2 to 7 years
      was done. The actual uncuffed endotracheal tube (ETT) size was compared with the
      predicted one, using both the ABF [ID (mm) = age (years)/4 + 4] and the HBF [ID
      (mm) = height (cm)/30 + 2]. RESULTS: ABF and HBF correctly predicted 50.8% and
      50.4% of ETT sizes (p = 1.0), whereas three sizes of tubes (one above and one
      below the predicted size) cover 95.8% and 93.5% of the patients, respectively (p
      = 0.24). In patients with FTT, both the ABF and HBF correctly predicted 56.6% of
      ETT sizes. CONCLUSION: Age- and height-based formula for estimating tube size in
      cardio-surgical children is equivalent and independent of physical development.
      Age-based formula as the simple method can be recommended. The availability of
      three tube sizes (one smaller one larger than estimated) should be ensured.

PMID- 22612010
TI  - Using blood loss pictogram for visual blood loss estimation in cesarean section.
AB  - OBJECTIVE: To determine whether using pictogram can improve visual estimation of
      blood loss in a mock cesarean setting and whether profession and clinical
      experience influence the accuracy of blood loss estimation. MATERIAL AND METHOD:
      Photographs of measured blood volume absorbed in different percentage of surface
      area of common surgical materials were taken and arranged in the table of
      pictogram. Pictures of seven cesarean scenarios were set with known blood volumes
      (20, 35, 60, 100, 350, 400, and 1200 ml) in different surgical materials. Forty
      nine participants from four professions had to view all seven pictures and
      quantitatively estimate blood volume pre-post using the pictogram. Percent error
      of estimated blood loss was analyzed. RESULTS: Before using the pictogram,
      tendency of underestimation, overestimation and accurate assessment in lower and
      higher blood loss volumes were 43.4%, 25.7%, and 30.9% respectively. There was a
      trend in overestimating blood loss at the lower volumes and underestimating or
      accurate estimating blood loss at higher volumes. Profession affected the
      accuracy in estimation of some small blood loss volumes but clinical experience
      had no influence. After using the pictogram, accurate estimation increased
      significantly from 30.9% to 61.8%. No difference in ability to determine blood
      loss in allprofessions and clinical experience. CONCLUSION: Estimated blood loss
      pictogram is a simple tool, easy to use for initial evaluation of blood loss in
      cesareans and can improve the accuracy of visual blood loss assessment
      significantly.

PMID- 22612011
TI  - Effects of phacoemulsification and intraocular lens implantation on intraocular
      pressure in primary angle closure glaucoma (PACG) patients.
AB  - OBJECTIVE: To investigate the effect of cataract surgery by phacoemulsification
      on the intraocular pressure (IOP) in primary angle closure glaucoma (PACG)
      patients. MATERIAL AND METHOD: Sixty PACG patients who underwent
      phacoemulsification between January 2004 and May 2009 were retrospectively
      reviewed. Pre- and post-operative visual acuity, IOP and number of anti-glaucoma
      medications were recorded. Lens thickness and anterior chamber depth (ACD) of pre
      operative were also recorded. Patients who had previous intraocular surgeries or
      complicated cataract surgeries were excluded. RESULTS: Visual acuity logMAR
      improved significantly (0.17, p < 0.01). Mean IOP after cataract surgery
      decreased significantly (4.50 mmHg, p < 0.01). There was no significant
      relationship between the decrease in IOP and lens thickness or ACD. Twenty
      percent of PACG patients were free of antiglaucoma medication after cataract
      surgery. CONCLUSION: Phacoemulsification not only improves the visual acuity in
      PACG patients but also reduces IOP and number of anti-glaucoma medications
      required significantly. The change in IOP does not significantly correlate with
      lens thickness or ACD.

PMID- 22612012
TI  - Anatomical considerations of the Thai fibula used as a fibula osteocutaneous free
      flap in mandibular reconstruction and dental implant placement.
AB  - OBJECTIVE: Although the fibula osteocutaneous free flap has many proven
      advantages in restoring mandibular defects, the dimension of available fibula is
      one of its limitations. The present study aimed to investigate the suitability of
      dimensions and the quality of harvested fibulae for mandibular reconstruction and
      dental implant placement in Thais. MATERIAL AND METHOD: One hundred fourteen
      fibulae of 57 adult Thai cadavers were dissected. Total fibular length and the
      length of harvested fibula were measured. Dimensions of the fibula cross sections
      available for dental implant placement were recorded. Additionally, the cortical
      bone thickness and densities of cortical and spongy bones of 60 fibulae were
      assayed using cone beam computed tomography scan images. RESULTS: Mean total
      fibular length and mean length of harvested fibulae were 34.2 +/- 2.3 cm and 18.2
      +/- 2.3 cm, respectively. A dental implant length of 7 to 10 mm could be placed
      in the fibula. The mean cortical bone thickness was 2.2 +/- 0.6 mm. The mean
      densities of the cortical and spongy bones were 614.4 +/- 148.8 HU and -600.6 +/-
      228.7 HU, respectively. CONCLUSION: The present study suggests that, in Thais, a
      harvested fibula of 16 to 20 cm in length is sufficient to provide bone for
      reconstructing defected mandible and the dental implant placement is 7 to 10 mm
      in length. The mean cortical and spongy bone densities of fibula are less than
      that of the mandible in previous reports. The result supports the clinical
      experience using the fibula as donor site for the mandibular reconstruction and
      dental implant placement.

PMID- 22612013
TI  - Anatomical variations of the V2 vertebral artery study by measuring the width of
      transverse foramen.
AB  - OBJECTIVE: To evaluate the incidence of anatomical variations of the V2 segment
      of the vertebral artery (VA) using dry bones. MATERIAL AND METHOD: The sample
      group was 181 cervical spines (equal 362 courses of VA), male 111 and female 70,
      average age 68 years old (range 26 to 95 years). The width of transverse foramens
      (TF) was visually inspected, starting at C7, looking upward to find the greatest
      width of TF meaning the beginning of V2. Then, measurements were taken of the TF
      width (AP, ML) followed by measurements of those of one level below and above.
      RESULTS: The VA entered the C6 TF in 89.0% (322 out of 362 courses). The
      variations level of entrance was observed in 11.0% of specimens (40 courses),
      with the level of C4, C5, and C7 TF in 1.1% (4 courses), 4.4% (16 courses), and
      5.5% (20 courses), respectively. Nineteen out of 40 VA (47.5%) of variations were
      on the left side and twenty-one (52.5%) were on the right side. Twenty-three out
      of 40 VA (57.5%) of variations were men and seventeen (42.5%) were women. The
      areas of TF filled with VA were significantly larger than before and after the
      entrance level (p < 0.0001). CONCLUSION: Anatomical variations of the V2 segment
      of the VA do exist at C4, C5, and C7. The awareness of this abnormality may
      reduce the risk of catastrophic intraoperative VA injury.

PMID- 22612014
TI  - Distinguishing small primary lung cancer from pulmonary tuberculoma using 64
      slices multidetector CT.
AB  - OBJECTIVE: To evaluate which CT findings help in distinguishing small primary
      lung cancer from tuberculoma. MATERIAL AND METHOD: Forty-two chest CT studies
      with pathological diagnosis of primary lung cancer (n = 27) and tuberculoma (n =
      15) were retrospectively reviewed by two radiologists who were blind to the
      pathological results. The CT findings of number; size, shape, border and location
      of the nodules, the presence or absence of satellite nodule, contrast
      enhancement, internal air bronchogram, internal calcification, internal
      cavitation, bronchovascular invasion, and bony destruction were evaluated.
      RESULTS: About 96% of primary lung cancer had a solitary lesion compared to only
      60% among tuberculoma (p < 0.05). The nodule size > 2-3 cm is more likely to be
      primary lung cancer compared with tuberculoma (p = 0.058). Both primary lung
      cancer and tuberculoma can occur in all lobes of both lungs but more frequently
      in the upper lobe, which has no statistically significant difference between
      these two groups. Tuberculoma seems to be round or polygonal shape and primary
      lung cancer is more likely to be lobulated shape. The smooth border nodule is
      found only in tuberculoma (27%) whereas 93% of primary lung cancer had spiculated
      border compared to 73% among tuberculoma (p < 0.05). Tuberculoma seems to have
      more satellite nodule than primary lung cancer (47% vs. 22%, p = 0.163). The
      enhancement of nodule and air bronchogram are significantly found in primary lung
      cancer compared with tuberculoma (p < 0.05). Tuberculoma seems to have dense
      central calcification and primary lung cancer seems to have punctate
      calcification (p < 0.05). Most of the primary lung cancer and tuberculoma do not
      have internal cavity. The presence of bronchovascular invasion was significantly
      found in primary lung cancer compared with tuberculoma (p < 0.05). No evidence of
      bony destruction was observed in both pulmonary tuberculoma and primary lung
      cancer groups. CONCLUSION: The solitary lesion size < 3 cm in diameter with
      spiculated border contrast enhancement, presence of air bronchogram, punctate
      calcification and bronchovascular invasion are useful CT findings for diagnosis
      of primary lung cancer However, the lesions with inconclusive findings, tissue
      diagnosis may be necessary.

PMID- 22612015
TI  - Pharmacokinetic of gabapentin 600 mg tablet in Thai healthy subjects.
AB  - BACKGROUND: Gabapentin is an antiepileptic drug. It is structurally similar to
      yaminobutyric acid (GABA), which crosses the blood-brain barrier. Gabapentin is
      absorbed into the blood by the L-amino acid transport system. The oral
      bioavailability of gabapentin displays dose-dependence. Plasma concentrations
      ofgabapentin are not directly proportional to dose. Therefore, pharmacokinetic of
      gabapentin is essential for patients who have to receive gabapentin 600 mg.
      OBJECTIVE: To investigate the pharmacokinetic of gabapentin 600 mg in Thai
      healthy subjects. MATERIAL AND METHOD: The present study was performed on 24
      healthy Thai male subjects who received a single oral dose of 600 mg gabapentin
      tablet. Serial blood samples were collected before and to 48 hours after drug
      administration. Plasma gabapentin concentrations were determined by automated
      High Performance Liquid Chromatography (HPLC) with UV detector after
      deproteinized with acetonitrile followed by derivatization with 1-fluoro-2,4
      dinitrobenzene. The relevant pharmacokinetic parameters were determined. RESULTS:
      The mean values of pharmacokinetic parameters (mean +/- SD) were 3.17 +/- 0.80
      hour (1.5 to 5.0 hour) for T; 4,853.58 +/- 1,369.67 ng/ml for Cm; 0.11 +/- 0.02
      hour for Kel, 6.62 +/- 1.87 hour (4.89 to 11.41 hour) for T1/2; 47,712.88 +/-
      12,853.61 ng.hour/ml for AUC0-t, 48,713.20 +/- 12,909.78 ng.hour/ml for AUC0-inf,
      5.24 +/- 1.32 L/hour for CI, and 49.28 +/- 15.98 L for Vd. CONCLUSION: The data
      show the pharmacokinetic parameters of gabapentin 600 mg. These data should be
      used to support the assignment of therapeutic purposes for patients who have to
      receive gabapentin 600 mg.

PMID- 22612016
TI  - Correlation between the action research arm test and the box and block test of
      upper extremity function in stroke patients.
AB  - OBJECTIVE: The objective of the present study was to determine the correlation
      between the scores of the Action Research Arm Test (ARAT) and the Box and Block
      Test (BBT), commonly used tests of upper extremity (UE)function. MATERIAL AND
      METHOD: Forty first-time subacute stroke patients without severe cognitive,
      language, or motion impairment were administered the ARAT and BBT before and
      after participating in a 4-week rehabilitation program. Their scores were
      analyzed by Wilcoxon sign-rank testing and by Spearman's rank correlation,
      standardized response mean, and scatter-plot analysis. RESULTS: The ARAT and the
      BBT scores have a high level of responsiveness to change and are highly
      correlated. The BBThas afloor effect compared with the ARAT while the ARAT has a
      small ceiling effect compared with the BBT CONCLUSION: The ARAT and the BBT
      scores have excellent concurrent validity and are highly responsive to change,
      indicating that the BBT can effectively assess UE function.

PMID- 22612017
TI  - The effects of lavender oil inhalation on emotional states, autonomic nervous
      system, and brain electrical activity.
AB  - OBJECTIVE: Investigate the effects of lavender oil on the central nervous system,
      autonomic nervous system, and mood responses in humans after inhalation. MATERIAL
      AND METHOD: Twenty healthy volunteers participated in the experiments. The
      present study assessed autonomic parameters such as blood pressure, heart rate,
      respiratory rate, and skin temperature to determine the arousal level of the
      autonomic nervous system. In addition, subjects were asked to estimate their mood
      responses such as feeling pleasant or unpleasant, uncomfortable, sensuality,
      relaxation, or refreshing in order to assess subjective behavioral arousal.
      Finally, electroencephalogram (EEG) was recorded from 31 electrodes on the scalp
      according to the international 10 to 20 system, and EEG power spectra were
      calculated by Fast Fourier Transform (FFT). Data was analyzed by comparing the
      effects of lavender oil on physiological and mood states with sweet almond oil.
      These assessments were measured before and after using paired t-test statistical
      procedure. RESULTS: The results revealed that lavender oil caused significant
      decreases of blood pressure, heart rate, and skin temperature, which indicated a
      decrease of autonomic arousal. In terms of mood responses, the subjects in the
      lavender oil group categorized themselves as more active, fresher relaxed than
      subjects just inhaling base oil. Compared with base oil, lavender oil increased
      the power of theta (4-8 Hz) and alpha (8-13 Hz) brain activities. The topographic
      map showed obviously more scattering power in alpha range waves particularly in
      bilateral temporal and central area. CONCLUSION: The findings provided evidence
      the relaxing effect of inhaling lavender oil.

PMID- 22612018
TI  - Laparoendoscopic single-site nephrectomy for patients with dialysis-dependent end
      stage renal disease.
AB  - OBJECTIVE: Assess the feasibility, safety, and outcome of laparoendoscpic single
      site (LESS) nephrectomy in high-risk patients with end-stage renal disease
      (ESRD), who have undergone continuous ambulatory peritoneal dialysis (CAPD) and
      hemodialysis (HD) treatment. MATERIAL AND METHOD: Between October 2009 and
      January 2010, a 62-year-old female and a 36-year-old male that had undergone CAPD
      and HD, respectively, consecutively underwent LESS nephrectomies. The medical
      records of the two patients were retrospectively reviewed. The indications for
      nephrectomy were that the non-functioning kidney was associated with a ureteric
      stone and distal ureteric stricture, respectively. Parameters examined were
      patient demographics, medical co-morbidities, operative outcomes, and
      complications. RESULTS: All procedures were completed successfully via
      transumbilical LESS laparoscopy. The operative times were 160 and 200 minutes,
      blood loss 200 and 50 mL, and postoperative hospital stay 6 and 14 days,
      respectively. No intraoperative complications were reported. The first patient
      who used CAPD before LESS nephrectomy for whom CAPD was successfully reinstated
      within two weeks postoperatively. No other catheter-related complications
      occurred. The second patient required a reoperation to evaluate the active
      bleeding on the fifth post-operative day, but could not find any blood vessel
      injuries. The bleeding was stopped from the platelet replacement. Pathological
      evaluation revealed chronic glomerulonephritis in each case. CONCLUSION: Less
      nephrectomy is a feasible technique with the advantages of less pain, shortened
      convalescence, improved cosmesis, and absence of wound complications.

PMID- 22612019
TI  - HELLP syndrome in pregnancy as a cause of sudden unexpected death and spontaneous
      hepatic rupture: A medico-legal autopsy case report.
AB  - This is the first reported medico-legal autopsy case in Thailand. It is a case of
      a 26-year-old Thai female with primigravida and 34 weeks gestational age that had
      sudden unexpected death. The laboratory investigations before death revealed
      evidence of hemolysis, which is decreased hematocrit, elevated lactate
      dehydrogenase (865 U/L), and low platelet count (8.7 x 10(9) cells/L). These
      findings were compatible with HELLP (Hemolysis, Elevated Liver enzymes, and Low
      Platelets) syndrome. The autopsy findings showed two ruptures of the right lobe
      of the liver hepatic subcapsular hematoma, rupture of Glisson's capsule, and
      massive hemoperitoneum with abruptio placentae. Histological features of liver
      and kidneys revealed specific characteristics that can assist the forensic
      pathologist to diagnose HELLP syndrome when laboratory examinations are not
      available.

PMID- 22612020
TI  - [Gene tests in cardiac rhythm disturbances--new international expert
      recommendations].
AB  - Gene testing is important in the diagnosis of prolonged QT syndrome and
      hypertrophic cardiomyopathy, which should be diagnosed already at an asymptomatic
      stage. An international expert group has recently given recommendations
      concerning the use of gene tests in the clinical diagnostics of cardiac rhythm
      disturbances and cardiomyopathies. In these patients diagnostics is demanding and
      time consuming due to familial aggregation of the diseases. Thus, to facilitate
      appropriate use of gene testing, the diagnostics should be centralized.

PMID- 22612021
TI  - [New antithrombotic drugs].
AB  - Platelet inhibitors and anticoagulants are called antithrombotic drugs. New
      platelet inhibitors prasugrel and ticagrelor are more effective than the
      traditional clopidogrel, but their use is also accompanied by more frequent
      bleeding complications. Varfarin has gained true competitors; new oral
      anticoagulants include dabigatran, rivaroxaban and apixaban. New anticoagulants
      are easier to use but clearly more expensive. The use of new anticoagulants is
      also accompanied by several potential problems that the clinician should be aware
      of.

PMID- 22612023
TI  - [Fabry disease].
AB  - Fabry disease is an X-linked inherited condition with the absence or reduction of
      alpha-galactosidase A- activity in lysosomes leading to accumulation of
      globotriaosylceramide and related neutral glycosphingolipids. Manifestations of
      Fabry disease include progressive renal and cardiac insufficiency, neuropathic
      pain, gastrointestinal symptoms, cerebral infarction and skin and pulmonary
      symptoms. First symptoms of Fabry disease usually appear in childhood. The
      symptoms in females may be as severe as in males. Early diagnosis of Fabry
      disease is important because enzyme replacement therapy can stabilize the
      condition and prevent progression of the disease.

PMID- 22612022
TI  - [Stable coronary artery disease--invasive treatment does not replace secondary
      prevention].
AB  - Secondary prevention, i.e. nonsmoking, exercise, weight control, correct
      nutrition and drugs affecting the prognosis, constitute the basis for the
      treatment of stable coronary artery disease. The most important drug affecting
      the prognosis is acetylsalicylic acid. Statin medication can be reduced on the
      basis of adverse effects only. Angiotensin convertase inhibitor medication is
      often forgotten in coronary artery disease patients who have undergone cardiac
      infarction or a temporary stage of cardiac insufficiency. Long-acting nitrate is
      not the first-line antianginal treatment, beta-blockers and calcium channel
      blockers being recommended instead.

PMID- 22612024
TI  - [Internet addiction].
AB  - Internet addiction is defined as uncontrolled and harmful use of Internet, which
      manifests in three forms: gaming, various sexual activities and excessive use of
      emails, chats or SMS messaging. Several studies have found that abuse of alcohol
      and other substances, depression and other health problems are associated with
      Internet addiction. In boys and men depression may be more a consequence of the
      addiction than a cause for it. ADHD seems to be a significant background factor
      for developing the condition. Because it is almost impossible to lead a life
      without Internet and computers nowadays, it is unrealistic to aim towards full
      abstinence. Treatment has generally followed the guidelines adapted for
      pathological gambling.

PMID- 22612025
TI  - [Superior semicircular canal dehiscence as a cause of hearing loss].
AB  - Superior semicircular canal dehiscence can be the cause of hearing loss and
      vertigo. Typical findings are conductive hearing loss and hyperacusis to bone
      conducted sounds. Also acute pressure- and sound-evoked vestibular symptoms may
      occur. We describe a middle-aged patient with a conductive hearing loss. A few
      basic examinations led to suspicion of superior canal dehiscence. Computerized
      tomographic (CT) scan revealed a pathologic third window in the superior
      semicircular canal.

PMID- 22612026
TI  - [Dabigatran and emergency operation on a peritonitis patient].
AB  - Dabigatran has been introduced into the prevention of stroke in patients with
      atrial fibrillation. Monitoring of the effect and reversing the action of
      dabigatran as well as management of an emergency operation and bleeding in a
      patient who is using the drug is demanding. In such patients, clinical guidelines
      for the treatment of acute bleeding are based on expert opinions. There is no
      antidote for dabigatran, but its effect can possibly be partly reversed with
      recombinant coagulation factor VIIa and dialysis. With increasing use of
      dabigatran, more frequent severe bleeding complications and problems in emergency
      operations are to be expected.

PMID- 22612027
TI  - [Update on current care guidelines: oral cancer].
AB  - Most oral malignancies are squamous cell carcinomas (OSCC). Incidence of OSCC is
      increasing in both genders, and survival rates remain poor. OSCC is frequently
      preceded by potentially malignant disorders (OPMD), which include leukoplakia,
      erythroplakia and lichen planus. OSCC is preventable because the risk factors are
      known: smoking and alcohol consumption, snuff and human papillomavirus
      infections. Fresh vegetables, fruit and fish provide protection from OSCC.
      Regular systematic examination is essential to the early detection of OSCC and
      OPMD. Treatment of oral cancers comprises either surgery alone, or combined with
      radiotherapy and chemotherapy. Management of patients with OPMD and treated OSCC
      include careful life-long follow-up.

PMID- 22612028
TI  - A single file system: the science of simplicity.

PMID- 22612029
TI  - Focus on: endodontics.

PMID- 22612030
TI  - Keeping dentistry in the hands of dentists.

PMID- 22612031
TI  - Dental organizations respond to Pew report.

PMID- 22612033
TI  - Reciprocating relieved reamers. The future of endodontic instrumentation.

PMID- 22612032
TI  - Methicillin-resistant Staphylococcus aureus. A continuing infection control
      challenge.
AB  - The ability of MRSA and other staphylococci to colonize, persist, and adapt to
      multiple environmental and tissue conditions has allowed for these bacteria to be
      virtually ubiquitous in their distribution. The effectiveness of commonly used
      antibiotics, such as penicillin, has continued to decline against infections
      caused by MRSA and increasingly resistant strains. The challenge for both dental
      and medical health professionals is to routinely apply proven, evidence-based
      infection control precautions. As mentioned earlier in this discussion, when
      compliance with effective aseptic technique practices improves, the patients and
      environments. Ensure that reusable equipment is not used for the care of another
      patient until it has been appropriately cleaned and reprocessed and that single
      use items are properly discarded. Clean and disinfect clinical contact surfaces
      that are not barrier-protected by using an environmental protection agency
      registered hospital disinfectant with a low- (ie, HIV and HBV label claims) to
      intermediate-level (ie, tuberculocidal claim) activity after each patient. When
      the surface is visibly contaminated with blood, an intermediate-incidence of
      detectable infections can be reduced. Microorganisms will continue to evolve and
      adapt in order to survive and thrive, sometimes at the expense of susceptible
      human hosts. The struggle is to constantly remain aware of impending infectious
      threats which may challenge current precautions, and maintain and improve the
      quality of infection control to minimize the potential for disease.

PMID- 22612034
TI  - Redesigning the macrostructure of dental implants.

PMID- 22612035
TI  - Small-diameter implants.

PMID- 22612036
TI  - Efficient core buildups. Sonic-activated composite resin in endodontically
      treated teeth.

PMID- 22612037
TI  - GP orthodontics: making a difference.

PMID- 22612038
TI  - Composite over-mold of the worn lower incisor.

PMID- 22612039
TI  - The creation of an emergence profile, Part I. Using an interim restoration as an
      aid to implant positioning.

PMID- 22612040
TI  - CAD/CAM restorative principles.

PMID- 22612041
TI  - A novel approach for a single-tooth provisional.

PMID- 22612042
TI  - Local antibiograms can reduce inappropriate antibiotic prescribing.

PMID- 22612045
TI  - Do electronic health records improve processes and outcomes  of preventive care?

PMID- 22612047
TI  - Information from your family doctor. What men should know about staying healthy.

PMID- 22612046
TI  - The adult well male examination.
AB  - The adult well male examination should incorporate evidence-based guidance toward
      the promotion of optimal health and well-being, including screening tests shown
      to improve health outcomes. Nearly one-third of men report not having a primary
      care physician. The medical history should include substance use; risk factors
      for sexually transmitted infections; diet and exercise habits; and symptoms of
      depression. Physical examination should include blood pressure and body mass
      index screening. Men with sustained blood pressures greater than 135/80 mm Hg
      should be screened for diabetes mellitus. Lipid screening is warranted in all men
      35 years and older, and in men 20 to 34 years of age who have cardiovascular risk
      factors. Ultrasound screening for abdominal aortic aneurysm should occur between
      65 and 75 years of age in men who have ever smoked. There is insufficient
      evidence to recommend screening men for osteoporosis or skin cancer. The U.S.
      Preventive Services Task Force has provisionally recommended against prostate
      specific antigen-based screening for prostate cancer because the harms of testing
      and overtreatment outweigh potential benefits. Screening for colorectal cancer
      should begin at 50 years of age in men of average risk and continue until at
      least 75 years of age. Screening should be performed by high-sensitivity fecal
      occult blood testing every year, flexible sigmoidoscopy every five years combined
      with [corrected] fecal occult blood testing every three years. [corrected]. The
      U.S. Preventive Services Task Force recommends against screening for testicular
      cancer and chronic obstructive pulmonary disease. Immunizations should be
      recommended according to guidelines from the Advisory Committee on Immunization
      Practices of the Centers for Disease Control and Prevention.

PMID- 22612048
TI  - Prevention of malaria in travelers.
AB  - There are approximately 300 million cases of malaria each year, resulting in 1
      million deaths worldwide. Family physicians often encounter patients preparing to
      travel to malaria-endemic regions. Physicians should have basic knowledge of
      parasite transmission and malaria prevention. The risk of malaria acquisition is
      based largely on geographic location and travel season. Most cases occur in sub
      Saharan Africa, the Indian subcontinent, and Southeast Asia between the months of
      May and December. Key elements in prevention include barrier protection and
      chemoprophylaxis. Travelers to malaria-endemic areas should be advised to use
      mosquito repellent at all times and bed netting at night. Prophylactic medication
      should be initiated before travel and continued after return. Travelers should be
      warned that malaria symptoms can present up to one year after a mosquito bite.
      Symptoms are vague, and may include fever, chills, arthralgias, and headaches.
      Travelers experiencing symptoms should seek prompt medical attention.

PMID- 22612049
TI  - Information from your family doctor. Preventing malaria during travel.

PMID- 22612050
TI  - Infectious endocarditis: diagnosis and treatment.
AB  - Infectious endocarditis results from bacterial or fungal infection of the
      endocardial surface of the heart and is associated with significant morbidity and
      mortality. Risk factors include the presence of a prosthetic heart valve,
      structural or congenital heart disease, intravenous drug use, and a recent
      history of invasive procedures. Endocarditis should be suspected in patients with
      unexplained fevers, night sweats, or signs of systemic illness. Diagnosis is made
      using the Duke criteria, which include clinical, laboratory, and
      echocardiographic findings. Antibiotic treatment of infectious endocarditis
      depends on whether the involved valve is native or prosthetic, as well as the
      causative microorganism and its antibiotic susceptibilities. Common blood culture
      isolates include Staphylococcus aureus, viridans Streptococcus, enterococci, and
      coagulase-negative staphylococci. Valvular structural and functional integrity
      may be adversely affected in infectious endocarditis, and surgical consultation
      is warranted in patients with aggressive or persistent infections, emboli, and
      valvular compromise or rupture. After completion of antibiotic therapy, patients
      should be educated about the importance of daily dental hygiene, regular visits
      to the dentist, and the need for antibiotic prophylaxis before certain
      procedures.

PMID- 22612051
TI  - Chronic rash in a middle-aged woman.

PMID- 22612052
TI  - Evaluation of newborns with preauricular skin lesions.

PMID- 22612053
TI  - ACCF/AHA update peripheral artery disease management guideline.

PMID- 22612054
TI  - Acupuncture may be helpful for patients with plantar fasciitis.

PMID- 22612056
TI  - The embodiment of focus: investigating the impact of leaning behavior on our
      cognitive state and other's perception of our cognitive state.
AB  - The emerging literature on embodied cognition highlights the role that the body
      plays in cognitive and affective processes. We investigated whether different
      body postures, specifically leaning postures thought to reflect different states
      of cognitive focus, can impact cognitive focus and task performance. In three
      experiments we confirmed that different postures are perceived reliably by others
      to convey distinct and different states of cognitive focus. However, the
      individuals who actually adopted the postures did not experience any subjective
      change in cognitive focus nor demonstrate any influence of leaning posture on
      performance across a range of tasks that varied in their naturalness and
      complexity. Only by instructing participants to adopt a posture associated with a
      focused or unfocused cognitive state did an association between performance and
      posture emerge. These data indicate that changes in one's body do not necessarily
      yield a reliable change in one's cognitive state, even when (a) those changes in
      body are reliably perceived by others as inducing a change in cognitive state,
      and (b) changes in cognitive state lead to robust changes in the body. In light
      of these findings, we propose two related accounts that point to leaning behavior
      as being the result of one's increasing need to focus. Thus, rather than
      influencing cognitive state, leaning behavior may instead reflect the embodiment
      of one's cognitive state of focus.

PMID- 22612055
TI  - Stability and spectroscopic properties of singly and doubly charged anions.
AB  - Using density functional theory and hybrid B3LYP exchange-correlation energy
      functional we have studied the structure, stability, and spectroscopic properties
      of singly and doubly charged anions composed of simple metal atoms (Na, Mg, Al)
      decorated with halogens such as Cl and pseudohalogens such as CN. Since
      pseudohalogens mimic the chemistry of halogen atoms, our objective is to see if
      pseudohalogens can also form superhalogens much as halogens do and if the
      critical size for a doubly charged anion depends upon the ligand. The electron
      affinities of MCl(n) (M = Na, Mg, Al) exceed the value of Cl for n >= (k + 1),
      where k is the normal valence of the metal atom. However, for M(CN)(n) complexes
      this is only true when n = k + 1. In addition, while the electron affinities and
      vertical detachment energies of MCl(n) complexes are close to each other, they
      are markedly different when Cl is replaced by pseudohalogen, CN. The origin of
      these anomalous results is found to be due to the large binding energy of
      cyanogen, (NCCN) molecule. Because of the tendency of CN molecules to dimerize,
      the ground state geometries of the neutral and anionic M(CN)(n) complexes are
      very different when their number exceed the normal valence of the metal atom.
      While our calculations support the conclusion of Skurski and co-workers that
      pseudohalogens can form the building blocks of superhalogens, we show that there
      is a limitation on the number of CN moieties where this is true. Equally
      important, we find large differences between the ground state geometries of the
      neutral and anionic M(CN)(n) complexes for n >= (k + 2) which could play an
      important role in interpreting future experimental data on M(CN)(n) complexes.
      This is because the electron affinity defined as the energy difference between
      the ground states of the anion and neutral can be very different from the
      adiabatic detachment energy defined as the energy difference between the ground
      state of the anion and its structurally similar neutral isomer.

PMID- 22612057
TI  - How visual and semantic information influence learning in familiar contexts.
AB  - Previous research using the contextual cuing paradigm has revealed both
      quantitative and qualitative differences in learning depending on whether
      repeated contexts are defined by letter arrays or real-world scenes. To clarify
      the relative contributions of visual features and semantic information likely to
      account for such differences, the typical contextual cuing procedure was adapted
      to use meaningless but nevertheless visually complex images. The data in reaction
      time and in eye movements show that, like scenes, such repeated contexts can
      trigger large, stable, and explicit cuing effects, and that those effects result
      from facilitated attentional guidance. Like simpler stimulus arrays, however,
      those effects were impaired by a sudden change of a repeating image's color
      scheme at the end of the learning phase (Experiment 1), or when the repeated
      images were presented in a different and unique color scheme across each
      presentation (Experiment 2). In both cases, search was driven by explicit memory.
      Collectively, these results suggest that semantic information is not required for
      conscious awareness of context-target covariation, but it plays a primary role in
      overcoming variability in specific features within familiar displays.

PMID- 22612058
TI  - The social perceptual salience effect.
AB  - Affective processes appraise the salience of external stimuli preparing the agent
      for action. So far, the relationship between stimuli, affect, and action has been
      mainly studied in highly controlled laboratory conditions. In order to find the
      generalization of this relationship to social interaction, we assess the
      influence of the salience of social stimuli on human interaction. We constructed
      reality ball game in a mixed reality space where pairs of people collaborated in
      order to compete with an opposing team. We coupled the players with team members
      with varying social salience by using both physical and virtual representations
      of remote players (i.e., avatars). We observe that, irrespective of the team
      composition, winners and losers display significantly different inter- and
      intrateam spatial behaviors. We show that subjects regulate their interpersonal
      distance to both virtual and physical team members in similar ways, but in
      proportion to the vividness of the stimulus. As an independent validation of this
      social salience effect, we show that this behavioral effect is also displayed in
      physiological correlates of arousal. In addition, we found a strong correlation
      between performance, physiology, and the subjective reports of the subjects. Our
      results show that proxemics is consistent with affective responses, confirming
      the existence of a social salience effect. This provides further support for the
      so-called law of apparent reality, and it generalizes it to the social realm,
      where it can be used to design more efficient social artifacts.

PMID- 22612059
TI  - Memory of gender and gait direction from biological motion: gender fades away but
      directions stay.
AB  - The delayed discrimination methodology has been used to demonstrate a high
      fidelity nondecaying visual short-term memory (VSTM) for so-called preattentive
      basic features. In the current Study, I show that the nondecaying high VSTM
      precision is not restricted to basic features by using the same method to measure
      memory precision for gait direction and gender-stereotypical gait patterns from
      high-level point-light walkers. Nondecaying VSTM of direction was found for
      delays up to 9 s whereas memory for gender decayed. For both tasks, reaction
      times (RTs) increased with the delay, but only gender RT took longer when the two
      walkers faced different directions to the line of sight as compared to when they
      faced the same direction. The results may reflect differences between local and
      global processes, or an ecologically valid strategy where VSTM resources focus on
      variables that change, such as tracking people's movements, rather than variables
      that are constant during short timescales, such as gender.

PMID- 22612061
TI  - Perioperative prophylaxis for percutaneous nephrolithotomy: randomized study
      concerning the drug and dosage.
AB  - PURPOSE: To compare sulbactam-ampicillin and cefuroxime antibiotics for
      prophylaxis of percutaneous nephrolithotomy (PCNL) and to find out the optimal
      regimen for antibiotic maintenance to prevent systemic inflammatory response
      syndrome (SIRS). PATIENTS AND METHODS: Between February 2010 and March 2011, a
      total of 198 patients in whom PCNL was performed were prospectively randomized
      into two main groups regarding the type of prophylactic antibiotic (group1:
      sulbactam-ampicillin, group 2: cefuroxime). Each group was further randomized
      according to duration of antibiotic maintenance (a: single dose prophylaxis, b:
      additional dose 12 hours after prophylaxis, c: beginning with prophylactic dose
      until the nephrostomy tube removal). Seven patients in whom purulent urine was
      obtained through the access needle were excluded from the study. Groups were
      compared in terms of stone- and operation-related factors as well as preoperative
      urine cultures, access cultures, stone cultures, postoperative urine cultures,
      and presence of SIRS. RESULTS: A total of 191 patients (group 1: 95, group 2: 96)
      were evaluated. Mean patient age, body mass index, stone size, and perioperative
      outcomes were similar. Positive culture rates did not differ between groups. SIRS
      was observed in 13 (43.3%) patients in group 1 and 17 patients (56.7%) in group 2
      (P=0.44). The relation between duration of antibiotic maintenance and SIRS
      development was not different in each group (P=0.95 for group 1, P: 0.39 for
      group 2). Urosepsis was observed in two patients, and one patient died because of
      septic shock. CONCLUSIONS: Sulbactam-ampicillin and cefuroxime antibiotics can be
      used safely for prophylaxis of PCNL. Single dose administration is sufficient.

PMID- 22612060
TI  - Conformational properties of nine purified cystathionine beta-synthase mutants.
AB  - Protein misfolding due to missense mutations is a common pathogenic mechanism in
      cystathionine beta-synthase (CBS) deficiency. In our previous studies, we
      successfully expressed, purified, and characterized nine CBS mutant enzymes
      containing the following patient mutations: P49L, P78R, A114V, R125Q, E176K,
      R266K, P422L, I435T, and S466L. These purified mutants exhibited full heme
      saturation, normal tetrameric assembly, and high catalytic activity. In this
      work, we used several spectroscopic and proteolytic techniques to provide a more
      thorough insight into the conformation of these mutant enzymes. Far-UV circular
      dichroism, fluorescence, and second-derivative UV spectroscopy revealed that the
      spatial arrangement of these CBS mutants is similar to that of the wild type,
      although the microenvironment of the chromophores may be slightly altered. Using
      proteolysis with thermolysin under native conditions, we found that the majority
      of the studied mutants is more susceptible to cleavage, suggesting their
      increased local flexibility or propensity for local unfolding. Interestingly, the
      presence of the CBS allosteric activator, S-adenosylmethionine (AdoMet),
      increased the rate of cleavage of the wild type and the AdoMet-responsive
      mutants, while the proteolytic rate of the AdoMet-unresponsive mutants was not
      significantly changed. Pulse proteolysis analysis suggested that the protein
      structure of the R125Q and E176K mutants is significantly less stable than that
      of the wild type and the other mutants. Taken together, the proteolytic data
      shows that the conformation of the pathogenic mutants is altered despite retained
      catalytic activity and normal tetrameric assembly. This study demonstrates that
      the proteolytic techniques are useful tools for the assessment of the biochemical
      penalty of missense mutations in CBS.

PMID- 22612063
TI  - The use of 'real-time' complement analysis to differentiate atypical haemolytic
      uraemic syndrome from other forms of thrombotic microangiopathies.

PMID- 22612062
TI  - Solution speciation controls mercury isotope fractionation of Hg(II) sorption to
      goethite.
AB  - The application of Hg isotope signatures as tracers for environmental Hg cycling
      requires the determination of isotope fractionation factors and mechanisms for
      individual processes. Here, we investigated Hg isotope fractionation of Hg(II)
      sorption to goethite in batch systems under different experimental conditions. We
      observed a mass-dependent enrichment of light Hg isotopes on the goethite surface
      relative to dissolved Hg (epsilon(202)Hg of -0.300/00 to -0.440/00) which was
      independent of the pH, chloride and sulfate concentration, type of surface
      complex, and equilibration time. Based on previous theoretical equilibrium
      fractionation factors, we propose that Hg isotope fractionation of Hg(II)
      sorption to goethite is controlled by an equilibrium isotope effect between
      Hg(II) solution species, expressed on the mineral surface by the adsorption of
      the cationic solution species. In contrast, the formation of outer-sphere
      complexes and subsequent conformation changes to different inner-sphere complexes
      appeared to have insignificant effects on the observed isotope fractionation. Our
      findings emphasize the importance of solution speciation in metal isotope
      sorption studies and suggest that the dissolved Hg(II) pool in soils and
      sediments, which is the most mobile and bioavailable, should be isotopically
      heavy, as light Hg isotopes are preferentially sequestered during binding to both
      mineral phases and natural organic matter.

PMID- 22612064
TI  - Scanning tunneling microscopy study and nanomanipulation of graphene-coated water
      on mica.
AB  - We study interfacial water trapped between a sheet of graphene and a muscovite
      (mica) surface using Raman spectroscopy and ultrahigh vacuum scanning tunneling
      microscopy (UHV-STM) at room temperature. We are able to image the graphene-water
      interface with atomic resolution, revealing a layered network of water trapped
      underneath the graphene. We identify water layer numbers with a carbon nanotube
      height reference. Under normal scanning conditions, the water structures remain
      stable. However, at greater electron energies, we are able to locally manipulate
      the water using the STM tip.

PMID- 22612066
TI  - Diagnostic imaging and pathogenesis of the traumatic intratumoural haemorrhage of
      schwannoma causing acute high radial nerve palsy: case report.
AB  - We describe the first report of haemorrhaged schwannoma presenting with acute
      high radial nerve palsy after traumatic injury of the upper arm. Anticoagulant
      therapy may induce intratumoural haemorrhage, resulting in symptomatic increases
      in size within the limited space of the upper arm. The radiological, surgical and
      pathological findings are discussed.

PMID- 22612065
TI  - Quantitative trait locus on distal chromosome 1 regulates the occurrence of
      spontaneous spike-wave discharges in DBA/2 mice.
AB  - PURPOSE: Most common forms of human epilepsy result from a complex combination of
      polygenetic and environmental factors. Quantitative trait locus (QTL) mapping is
      a first step toward the nonbiased discovery of epilepsy-related candidate genes.
      QTL studies of susceptibility to induced seizures in mouse strains have
      consistently converged on a distal region of chromosome 1 as a major phenotypic
      determinant; however, its influence on spontaneous epilepsy remains unclear. In
      the present study we characterized the influence of allelic variations within
      this QTL, termed Szs1, on the occurrence of spontaneous spike-wave discharges
      (SWDs) characteristic of absence seizures in DBA/2 (D2) mice. METHODS: We
      analyzed SWD occurrence and patterns in freely behaving D2, C57BL/6 (B6) and the
      congenic strains D2.B6-Szs1 and B6.D2-Szs1. KEY FINDINGS: We showed that congenic
      manipulation of the Szs1 locus drastically reduced the number and the duration of
      SWDs in D2.B6-Szs1 mice, which are homozygous for Szs1 from B6 strain on a D2
      strain background. However, it failed to induce the full expression of SWDs in
      the reverse congenic animals B6.D2-Szs1. SIGNIFICANCE: Our results demonstrate
      that the occurrence of SWDs in D2 animals is under polygenic control and,
      therefore, the D2 and B6 strains might be a useful model to dissect the genetic
      determinants of polygenic SWDs characteristic of typical absence seizures.
      Furthermore, we point to the existence of epistatic interactions between at least
      one modifier gene within Szs1 and genes within unlinked QTLs in regulating the
      occurrence of spontaneous nonconvulsive forms of epilepsies.

PMID- 22612067
TI  - Lesson learnt following diagnostic failure of a case of acute abdomen in
      pregnancy.

PMID- 22612068
TI  - Infantile osteoma cutis as a presentation of a GNAS mutation.
AB  - We report a case of osteoma cutis associated with a GNAS mutation in a 7-month
      old boy. The patient displayed no other laboratory or physical abnormalities to
      suggest other GNAS-associated disorders of cutaneous ossification, including
      Albright's hereditary osteodystrophy or pseudohypoparathyroidism 1A, although a
      history of intrauterine growth restriction was troubling for progressive osseous
      heteroplasia. A review of the clinical and laboratory manifestations of these
      disorders is discussed, as well as differentiating features.

PMID- 22612069
TI  - Optimizing megakaryocyte polyploidization by targeting multiple pathways of
      cytokinesis.
AB  - BACKGROUND: Large-scale in vitro production of platelets (PLTs) from cord blood
      stem cells is one goal of stem cell research. One step toward this goal will be
      to produce polyploid megakaryocytes capable of releasing high numbers of PLTs.
      Megakaryocyte polyploidization requires distinct cytoskeletal and cellular
      mechanisms, including actin polymerization, myosin activation, microtubule
      formation, and increased DNA production. In this study we variably combined
      inhibition of these principal mechanisms of cytokinesis with the goal of driving
      polyploidization in megakaryocytes. STUDY DESIGN AND METHODS: Megakaryocytes were
      derived from umbilical cord blood and cultured with reagents that inhibit
      distinct mechanisms of cytokinesis: Rho-Rock inhibitor (RRI), Src inhibitor (SI),
      nicotinamide (NIC), aurora B inhibitor (ABI), and myosin light chain kinase
      inhibitor (MLCKI). Combinations of reagents were used to determine their
      interactions and to maximize megakaryocyte ploidy. RESULTS: Treatment with RRI,
      NIC, SI, and ABI, but not with MLCKI, increased the final ploidy and RRI was the
      most effective single reagent. RRI and MLCKI, both inhibitors of MLC activation,
      resulted in opposite ploidy outcomes. Combinations of reagents also increased
      ploidy and the use of NIC, SI, and ABI was as effective as RRI alone. Addition of
      MLCKI to NIC, SI, and ABI reached the highest level of polyploidization.
      CONCLUSION: Megakaryocyte polyploidization results from modulation of a
      combination of distinct cytokinesis pathways. Reagents targeting distinct
      cytoskeletal pathways produced additive effects in final megakaryocyte ploidy.
      The RRI, however, showed no additive effect but produced a high final ploidy due
      to overlapping inhibition of multiple cytokinesis pathways.

PMID- 22612070
TI  - Liquid chromatography-mass spectrometry based metabolomics study of cloned versus
      normal pigs fed either restricted or ad libitum high-energy diets.
AB  - Genetically identical cloned pigs should in principle eliminate biological
      variation and provide more pronounced effects when subjected to, e.g., dietary
      interventions, but little is known about how phenotype and phenotypic variation
      is affected by cloning. Therefore, an investigation of the metabolome of cloned
      pigs compared to normal control pigs was performed to elucidate the variation and
      possible differences in the metabolic phenotypes during a dietary intervention. A
      total of 19 control pigs and 17 cloned pigs were given the same high-energy dense
      diet either ad libitum or in a restricted manner (60% of ad libitum) for ~6
      months, and plasma was subjected to liquid chromatography-mass spectrometry
      nontargeted metabolomics and biochemical analyses. Low systemic levels of IGF-1
      could indicate altered growth conditions and energy metabolism in cloned pigs. In
      response to ad libitum feeding, clones had a decreased energy intake and lower
      weight gain compared to controls, and plasma lipid profiles were changed
      accordingly. Elevated lactate and decreased creatine levels implied an increased
      anaerobic metabolism in ad libitum fed clones. Less interindividual variation
      between cloned pigs was however not established, suggesting a strong role for
      epigenetics and/or the gut microbiota to develop variation.

PMID- 22612071
TI  - Effectiveness of theophylline in preventing contrast-induced nephropathy after
      coronary angiographic procedures.
AB  - BACKGROUND: Contrast-induced nephropathy (CIN) is the third most common cause of
      hospital acquired acute renal failure and is associated with increased morbidity
      and mortality. The use of theophylline for prevention of CIN has yielded
      conflicting results. This study aimed at examining the effectiveness of
      theophylline in prevention of CIN when added to IV hydration and N-acetylcysteine
      (NAC). METHODS: Patients with stable serum creatinine and at least moderate risk
      for CIN according to Mehran's risk score were included in this parallel group,
      1:1, single-blind, randomized controlled trial. All patients received IV
      hydration (1 mL/kg per hour for 24 hours) and NAC (600 mg bid for 2 days).
      Patients were randomized to placebo (group P) or theophylline (200 mg in 100 mL
      0.9% saline, as IV infusion 30 minutes before contrast medium (CM)
      administration; group T). Patients underwent standard coronary angiography +/-
      angioplasty. Serum creatinine (SCr) was assessed just before and 72 hours after
      contrast administration and estimated glomerular filtration rate (eGFR) was
      calculated. RESULTS: This study included 60 patients with mean SCr 1.44 +/- 0.7
      mg/dL and eGFR 60.2 +/- 29.2 mL/min. Mean SCr among group T was 1.54 +/- 0.7
      mg/dL with eGFR 58.6 +/- 28.6 mL/min, while group P showed mean SCr of 1.34 +/-
      0.7 mg/dL and eGFR of 61.8 +/- 30.1 mL/min. Among group P, 6 (20%) patients
      developed CIN while none of the patients in group T developed CIN. In comparison
      to placebo, theophylline significantly decreased SCr (P = 0.0001) and increased
      eGFR (P = 0.001) at 72 hours. Multivariate regression analysis showed that
      receiving placebo instead of theophylline, anemia, congestive heart failure,
      chronic renal impairment, and high-contrast load are all independent predictors
      for deteriorating renal function after CM administration. CONCLUSION:
      Theophylline seems to be an effective prophylaxis against CIN for moderate- and
      high-risk patients undergoing coronary angiography or angioplasty. It offers
      additive protection when added to IV hydration and NAC.

PMID- 22612072
TI  - Adeno-associated virus-mediated gene delivery of the human ND4 complex I subunit
      in rabbit eyes.
AB  - BACKGROUND: To assess intravitreal injection dose and safety of recombinant adeno
      associated virus-mediated gene delivery of human NADH dehydrogenase subunit 4
      (ND4) in rabbit eyes. METHODS: An open reading frame for human ND4 or adeno
      associated virus-green fluorescent protein were fused to the mitochondrial
      targeting sequence and packed into separate adeno-associated virus capsids.
      Rabbits of three treatment groups were administered 0.1 mL adeno-associated virus
      ND4, 0.1 mL adeno-associated virus-green fluorescent protein or 0.1 mL vehicle
      via intravitreal injection, respectively. The safety of recombinant
      adenoassociated virus-mediated gene delivery of human ND4 in rabbit eyes was
      assessed with a slit-lamp microscope and direct ophthalmoscope, measurements of
      intraocular pressure and flash visual evoked potential, and optical coherence
      tomography. The mRNA and protein expressions of human ND4 in the retina of
      rabbits were determined with real-time polymer chain reaction (PCR),
      immunofluorescence and Western blot. RESULTS: No complications occurred in any of
      the three treatment groups after the intravitreal injection. At 1-month post
      injection, no significant difference in the mean thickness of retinal nerve fibre
      layer was found among the three groups. Results of the visual evoked potential
      test showed that there was no difference in the latency of the visual P100 wave
      among the three groups. Real-time PCR, immunofluorescence and Western blot
      analyses verified the expressions of ND4 and green fluorescent protein in the
      retinal nerve fibre layer. CONCLUSIONS: Intravitreal injection of adeno
      associated virus-ND4 expression vectors was effectively and safely performed in
      our study. The data on the dose and method of intravitreal injection from our
      study will provide a valuable reference for clinical intravitreal injection of
      adeno-associated virus-ND4 for the treatment of Leber's hereditary optic
      neuropathy.

PMID- 22612074
TI  - Replica exchange with nonequilibrium switches: enhancing equilibrium sampling by
      increasing replica overlap.
AB  - We describe a replica exchange strategy where trial swap configurations are
      generated by nonequilibrium switching simulations. By devoting simulation time to
      the switching simulations, one can systematically increase an effective overlap
      between replicas, which leads to an increased exchange acceptance rate and less
      correlated equilibrium samples. In this paper, we derive our method for a general
      class of stochastic dynamics, and discuss various strategies for enhancing
      replica overlap through novel dynamical schemes and prudent choices of switching
      protocols. We then demonstrate our method on a model system of alanine dipeptide
      in implicit solvent, characterizing decreases in data correlations and gains in
      sampling efficiency.

PMID- 22612073
TI  - Communication: a minimal model for the diffusion-relaxation backbone dynamics of
      proteins.
AB  - We present a model for the local diffusion-relaxation dynamics of the C(alpha)
      atoms in proteins describing both the diffusive short-time dynamics and the
      asymptotic long-time relaxation of the position autocorrelation functions. The
      relaxation rate spectra of the latter are represented by shifted gamma
      distributions, where the standard gamma distribution describes anomalous slow
      relaxation in macromolecular systems of infinite size and the shift accounts for
      a smallest local relaxation rate in macromolecules of finite size. The resulting
      autocorrelation functions are analytic for any time t >= 0. Using results from a
      molecular dynamics simulation of lysozyme, we demonstrate that the model fits the
      position autocorrelation functions of the C(alpha)-atoms exceptionally well and
      reveals moreover a strong correlation between the residue's solvent-accessible
      surface and the fitted model parameters.

PMID- 22612075
TI  - A new multiscale modeling method for simulating the loss processes in polymer
      solar cell nanodevices.
AB  - The photoelectric power conversion efficiency of polymer solar cells is till now,
      compared to conventional inorganic solar cells, still relatively low with maximum
      values ranging from 7% to 8%. This essentially relates to the existence of
      exciton and charge carrier loss phenomena, reducing the performance of polymer
      solar cells significantly. In this paper we introduce a new computer simulation
      technique, which permits to explore the causes of the occurrence of such
      phenomena at the nanoscale and to design new photovoltaic materials with
      optimized opto-electronic properties. Our approach consists in coupling a
      mesoscopic field-theoretic method with a suitable dynamic Monte Carlo algorithm,
      to model the elementary photovoltaic processes. Using this algorithm, we
      investigate the influence of structural characteristics and different device
      conditions on the exciton generation and charge transport efficiencies in case of
      a novel nanostructured polymer blend. More specifically, we find that the
      disjunction of continuous percolation paths leads to the creation of dead ends,
      resulting in charge carrier losses through charge recombination. Moreover, we
      observe that defects are characterized by a low exciton dissociation efficiency
      due to a high charge accumulation, counteracting the charge generation process.
      From these observations, we conclude that both the charge carrier loss and the
      exciton loss phenomena lead to a dramatic decrease in the internal quantum
      efficiency. Finally, by analyzing the photovoltaic behavior of the nanostructures
      under different circuit conditions, we demonstrate that charge injection
      significantly determines the impact of the defects on the solar cell performance.

PMID- 22612076
TI  - Equation of state of charged colloidal suspensions and its dependence on the
      thermodynamic route.
AB  - The thermodynamic properties of highly charged colloidal suspensions in contact
      with a salt reservoir are investigated in the framework of the renormalized
      Jellium model (RJM). It is found that the equation of state is very sensitive to
      the particular thermodynamic route used to obtain it. Specifically, the osmotic
      pressure calculated within the RJM using the contact value theorem can be very
      different from the pressure calculated using the Kirkwood-Buff fluctuation
      relations. On the other hand, Monte Carlo simulations show that both the
      effective pair potentials and the correlation functions are accurately predicted
      by the RJM. It is suggested that the lack of self-consistency in the
      thermodynamics of the RJM is a result of neglected electrostatic correlations
      between the counterions and coions.

PMID- 22612077
TI  - Spin densities from subsystem density-functional theory: assessment and
      application to a photosynthetic reaction center complex model.
AB  - Subsystem density-functional theory (DFT) is a powerful and efficient alternative
      to Kohn-Sham DFT for large systems composed of several weakly interacting
      subunits. Here, we provide a systematic investigation of the spin-density
      distributions obtained in subsystem DFT calculations for radicals in explicit
      environments. This includes a small radical in a solvent shell, a pi-stacked
      guanine-thymine radical cation, and a benchmark application to a model for the
      special pair radical cation, which is a dimer of bacteriochlorophyll pigments,
      from the photosynthetic reaction center of purple bacteria. We investigate the
      differences in the spin densities resulting from subsystem DFT and Kohn-Sham DFT
      calculations. In these comparisons, we focus on the problem of overdelocalization
      of spin densities due to the self-interaction error in DFT. It is demonstrated
      that subsystem DFT can reduce this problem, while it still allows to describe
      spin-polarization effects crossing the boundaries of the subsystems. In practical
      calculations of spin densities for radicals in a given environment, it may thus
      be a pragmatic alternative to Kohn-Sham DFT calculations. In our calculation on
      the special pair radical cation, we show that the coordinating histidine residues
      reduce the spin-density asymmetry between the two halves of this system, while
      inclusion of a larger binding pocket model increases this asymmetry. The
      unidirectional energy transfer in photosynthetic reaction centers is related to
      the asymmetry introduced by the protein environment.

PMID- 22612078
TI  - Hybrid coupled cluster methods: combining active space coupled cluster methods
      with coupled cluster singles, doubles, and perturbative triples.
AB  - Based on the coupled-cluster singles, doubles, and a hybrid treatment of triples
      (CCSD(T)-h) method developed by us [J. Shen, E. Xu, Z. Kou, and S. Li, J. Chem.
      Phys. 132, 114115 (2010); and ibid. 133, 234106 (2010); and ibid. 134, 044134
      (2011)], we developed and implemented a new hybrid coupled cluster (CC) method,
      named CCSD(T)q-h, by combining CC singles and doubles, and active triples and
      quadruples (CCSDtq) with CCSD(T) to deal with the electronic structures of
      molecules with significant multireference character. These two hybrid CC methods
      can be solved with non-canonical and canonical MOs. With canonical MOs, the
      CCSD(T)-like equations in these two methods can be solved directly without
      iteration so that the storage of all triple excitation amplitudes can be avoided.
      A practical procedure to divide canonical MOs into active and inactive subsets is
      proposed. Numerical calculations demonstrated that CCSD(T)-h with canonical MOs
      can well reproduce the corresponding results obtained with non-canonical MOs. For
      three atom exchange reactions, we found that CCSD(T)-h can offer a significant
      improvement over the popular CCSD(T) method in describing the reaction barriers.
      For the bond-breaking processes in F(2) and H(2)O, our calculations demonstrated
      that CCSD(T)q-h is a good approximation to CCSDTQ over the entire bond
      dissociation processes.

PMID- 22612079
TI  - Trapping photon-dressed Dirac electrons in a quantum dot studied by coherent two
      dimensional photon echo spectroscopy.
AB  - We study the localization of dressed Dirac electrons in a cylindrical quantum dot
      (QD) formed on monolayer and bilayer graphene by spatially different potential
      profiles. Short lived excitonic states which are too broad to be resolved in
      linear spectroscopy are revealed by cross peaks in the photon-echo nonlinear
      technique. Signatures of the dynamic gap in the two-dimensional spectra are
      discussed. The effect of the Coulomb induced exciton-exciton scattering and the
      formation of biexciton molecules are demonstrated.

PMID- 22612080
TI  - Ionization energy of atoms obtained from GW self-energy or from random phase
      approximation total energies.
AB  - A systematic evaluation of the ionization energy within the GW approximation is
      carried out for the first row atoms, from H to Ar. We describe a Gaussian basis
      implementation of the GW approximation, which does not resort to any further
      technical approximation, besides the choice of the basis set for the electronic
      wavefunctions. Different approaches to the GW approximation have been implemented
      and tested, for example, the standard perturbative approach based on a prior mean
      field calculation (Hartree-Fock GW@HF or density-functional theory GW@DFT) or the
      recently developed quasiparticle self-consistent method (QSGW). The highest
      occupied molecular orbital energies of atoms obtained from both GW@HF and QSGW
      are in excellent agreement with the experimental ionization energy. The lowest
      unoccupied molecular orbital energies of the singly charged cation yield a
      noticeably worse estimate of the ionization energy. The best agreement with
      respect to experiment is obtained from the total energy differences within the
      random phase approximation functional, which is the total energy corresponding to
      the GW self-energy. We conclude with a discussion about the slight concave
      behavior upon number electron change of the GW approximation and its consequences
      upon the quality of the orbital energies.

PMID- 22612081
TI  - Potential flux landscapes determine the global stability of a Lorenz chaotic
      attractor under intrinsic fluctuations.
AB  - We developed a potential flux landscape theory to investigate the dynamics and
      the global stability of a chemical Lorenz chaotic strange attractor under
      intrinsic fluctuations. Landscape was uncovered to have a butterfly shape. For
      chaotic systems, both landscape and probabilistic flux are crucial to the
      dynamics of chaotic oscillations. Landscape attracts the system down to the
      chaotic attractor, while flux drives the coherent motions along the chaotic
      attractors. Barrier heights from the landscape topography provide a quantitative
      measure for the robustness of chaotic attractor. We also found that the entropy
      production rate and phase coherence increase as the molecular numbers increase.
      Power spectrum analysis of autocorrelation function provides another way to
      quantify the global stability of chaotic attractor. We further found that limit
      cycle requires more flux and energy to sustain than the chaotic strange
      attractor. Finally, by detailed analysis we found that the curl probabilistic
      flux may provide the origin of the chaotic attractor.

PMID- 22612082
TI  - Ab initio quantum dynamics using coupled-cluster.
AB  - The curse of dimensionality (COD) limits the current state-of-the-art ab initio
      propagation methods for non-relativistic quantum mechanics to relatively few
      particles. For stationary structure calculations, the coupled-cluster (CC) method
      overcomes the COD in the sense that the method scales polynomially with the
      number of particles while still being size-consistent and extensive. We
      generalize the CC method to the time domain while allowing the single-particle
      functions to vary in an adaptive fashion as well, thereby creating a highly
      flexible, polynomially scaling approximation to the time-dependent Schrodinger
      equation. The method inherits size-consistency and extensivity from the CC
      method. The method is dubbed orbital-adaptive time-dependent coupled-cluster, and
      is a hierarchy of approximations to the now standard multi-configurational time
      dependent Hartree method for fermions. A numerical experiment is also given.

PMID- 22612083
TI  - Generalized Gibbs state with modified Redfield solution: exact agreement up to
      second order.
AB  - A novel scheme for the steady state solution of the standard Redfield quantum
      master equation is developed which yields agreement with the exact result for the
      corresponding reduced density matrix up to second order in the system-bath
      coupling strength. We achieve this objective by use of an analytic continuation
      of the off-diagonal matrix elements of the Redfield solution towards its diagonal
      limit. Notably, our scheme does not require the provision of yet higher order
      relaxation tensors. Testing this modified method for a heat bath consisting of a
      collection of harmonic oscillators we assess that the system relaxes towards its
      correct coupling-dependent, generalized quantum Gibbs state in second order. We
      numerically compare our formulation for a damped quantum harmonic system with the
      nonequilibrium Green's function formalism: we find good agreement at low
      temperatures for coupling strengths that are even larger than expected from the
      very regime of validity of the second-order Redfield quantum master equation. Yet
      another advantage of our method is that it markedly reduces the numerical
      complexity of the problem; thus, allowing to study efficiently large-sized system
      Hilbert spaces.

PMID- 22612084
TI  - Construction of high-dimensional neural network potentials using environment
      dependent atom pairs.
AB  - An accurate determination of the potential energy is the crucial step in computer
      simulations of chemical processes, but using electronic structure methods on-the
      fly in molecular dynamics (MD) is computationally too demanding for many systems.
      Constructing more efficient interatomic potentials becomes intricate with
      increasing dimensionality of the potential-energy surface (PES), and for numerous
      systems the accuracy that can be achieved is still not satisfying and far from
      the reliability of first-principles calculations. Feed-forward neural networks
      (NNs) have a very flexible functional form, and in recent years they have been
      shown to be an accurate tool to construct efficient PESs. High-dimensional NN
      potentials based on environment-dependent atomic energy contributions have been
      presented for a number of materials. Still, these potentials may be improved by a
      more detailed structural description, e.g., in form of atom pairs, which directly
      reflect the atomic interactions and take the chemical environment into account.
      We present an implementation of an NN method based on atom pairs, and its
      accuracy and performance are compared to the atom-based NN approach using two
      very different systems, the methanol molecule and metallic copper. We find that
      both types of NN potentials provide an excellent description of both PESs, with
      the pair-based method yielding a slightly higher accuracy making it a competitive
      alternative for addressing complex systems in MD simulations.

PMID- 22612085
TI  - The three-electron harmonium atom: the lowest-energy doublet and quadruplet
      states.
AB  - Calculations of sub-MUhartree accuracy employing explicitly correlated Gaussian
      lobe functions produce comprehensive data on the energy E(omega), its components,
      and the one-electron properties of the two lowest-energy states of the three
      electron harmonium atom. The energy computations at 19 values of the confinement
      strength omega ranging from 0.001 to 1000.0, used in conjunction with a recently
      proposed robust interpolation scheme, yield explicit approximants capable of
      estimating E(omega) and the potential energy of the harmonic confinement within a
      few tenths of MUhartree for any omega >= 0.001, the respective errors for the
      kinetic energy and the potential energy of the electron-electron repulsion not
      exceeding 2 MUhartrees. Thanks to the correct omega -> 0 asymptotics incorporated
      into the approximants, comparable accuracy is expected for values of omega
      smaller than 0.001. Occupation numbers of the dominant natural spinorbitals and
      two different measures of electron correlation are also computed.

PMID- 22612086
TI  - The multiscale coarse-graining method. VIII. Multiresolution hierarchical basis
      functions and basis function selection in the construction of coarse-grained
      force fields.
AB  - The multiscale coarse-graining (MS-CG) method is a method for determining the
      effective potential energy function for a coarse-grained (CG) model of a
      molecular system using data obtained from molecular dynamics simulation of the
      corresponding atomically detailed model. The coarse-grained potential obtained
      using the MS-CG method is a variational approximation for the exact many-body
      potential of mean force for the coarse-grained sites. Here we propose a new
      numerical algorithm with noise suppression capabilities and enhanced numerical
      stability for the solution of the MS-CG variational problem. The new method,
      which is a variant of the elastic net method [Friedman et al., Ann. Appl. Stat.
      1, 302 (2007)], allows us to construct a large basis set, and for each value of a
      so-called "penalty parameter" the method automatically chooses a subset of the
      basis that is most important for representing the MS-CG potential. The size of
      the subset increases as the penalty parameter is decreased. The appropriate value
      to choose for the penalty parameter is the one that gives a basis set that is
      large enough to fit the data in the simulation data set without fitting the
      noise. This procedure provides regularization to mitigate potential numerical
      problems in the associated linear least squares calculation, and it provides a
      way to avoid fitting statistical error. We also develop new basis functions that
      are similar to multiresolution Haar functions and that have the differentiability
      properties that are appropriate for representing CG potentials. We demonstrate
      the feasibility of the combined use of the elastic net method and the
      multiresolution basis functions by performing a variational calculation of the CG
      potential for a relatively simple system. We develop a method to choose the
      appropriate value of the penalty parameter to give the optimal basis set. The
      combined effect of the new basis functions and the regularization provided by the
      elastic net method opens the possibility of using very large basis sets for
      complicated CG systems with many interaction potentials without encountering
      numerical problems in the variational calculation.

PMID- 22612087
TI  - The multiscale coarse-graining method. IX. A general method for construction of
      three body coarse-grained force fields.
AB  - The multiscale coarse-graining (MS-CG) method is a method for constructing a
      coarse-grained (CG) model of a system using data obtained from molecular dynamics
      simulations of the corresponding atomically detailed model. The formal
      statistical mechanical derivation of the method shows that the potential energy
      function extracted from an MS-CG calculation is a variational approximation for
      the true potential of mean force of the CG sites, one that becomes exact in the
      limit that a complete basis set is used in the variational calculation if enough
      data are obtained from the atomistic simulations. Most applications of the MS-CG
      method have employed a representation for the nonbonded part of the CG potential
      that is a sum of all possible pair interactions. This approach, despite being
      quite successful for some CG models, is inadequate for some others. Here we
      propose a systematic method for including three body terms as well as two body
      terms in the nonbonded part of the CG potential energy. The current method is
      more general than a previous version presented in a recent paper of this series
      [L. Larini, L. Lu, and G. A. Voth, J. Chem. Phys. 132, 164107 (2010)], in the
      sense that it does not make any restrictive choices for the functional form of
      the three body potential. We use hierarchical multiresolution functions that are
      similar to wavelets to develop very flexible basis function expansions with both
      two and three body basis functions. The variational problem is solved by a
      numerical technique that is capable of automatically selecting an appropriate
      subset of basis functions from a large initial set. We apply the method to two
      very different coarse-grained models: a solvent free model of a two component
      solution made of identical Lennard-Jones particles and a one site model of SPC/E
      water where a site is placed at the center of mass of each water molecule. These
      calculations show that the inclusion of three body terms in the nonbonded CG
      potential can lead to significant improvement in the accuracy of CG potentials
      and hence of CG simulations.

PMID- 22612088
TI  - The multiscale coarse-graining method. X. Improved algorithms for constructing
      coarse-grained potentials for molecular systems.
AB  - The multiscale coarse-graining (MS-CG) method uses simulation data for an
      atomistic model of a system to construct a coarse-grained (CG) potential for a
      coarse-grained model of the system. The CG potential is a variational
      approximation for the true potential of mean force of the degrees of freedom
      retained in the CG model. The variational calculation uses information about the
      atomistic positions and forces in the simulation data. In principle, the
      resulting MS-CG potential will be an accurate representation of the true CG
      potential if the basis set for the variational calculation is complete enough and
      the canonical distribution of atomistic states is well sampled by the data set.
      In practice, atomistic configurations that have very high potential energy are
      not sampled. As a result there usually is a region of CG configuration space that
      is not sampled and about which the data set contains no information regarding the
      gradient of the true potential. The MS-CG potential obtained from a variational
      calculation will not necessarily be accurate in this unsampled region. A priori
      considerations make it clear that the true CG potential of mean force must be
      very large and positive in that region. To obtain an MS-CG potential whose
      behavior in the sampled region is determined by the atomistic data set, and whose
      behavior in the unsampled region is large and positive, it is necessary to
      intervene in the variational calculation in some way. In this paper, we discuss
      and compare two such methods of intervention, which have been used in previous MS
      CG calculations for dealing with nonbonded interactions. For the test systems
      studied, the two methods give similar results and yield MS-CG potentials that are
      limited in accuracy only by the incompleteness of the basis set and the
      statistical error of associated with the set of atomistic configurations used.
      The use of such methods is important for obtaining accurate CG potentials.

PMID- 22612089
TI  - Full-dimensional quantum dynamics study of exchange processes for the D + H2O and
      D + HOD reactions.
AB  - The exchange processes of D + H(2)O and D + HOD reactions are studied using
      initial state-selected time-dependent wave packet approach in full dimension. The
      total reaction probabilities for different partial waves, together with the
      integral cross sections, are obtained both by the centrifugal sudden (CS)
      approximation and exact coupled-channel (CC) calculations, for the H(2)O(HOD)
      reactant initially in the ground rovibrational state. In the CC calculations,
      small resonance peaks in the reaction probabilities and quick diminishing of the
      resonance peaks with the increase of total angular momenta J do not lead to clear
      step-like features just above the threshold in the cross sections for the title
      reactions, which are different in other isotopically substituted reactions where
      the hydrogen atom was included as the reactant instead of the deuterium atom [B.
      Fu, Y. Zhou, and D. H. Zhang, Chem. Sci. 3, 270 (2012); B. Fu and D. H. Zhang, J.
      Phys. Chem. A 116, 820 (2012)]. It is interesting that the shape resonance
      induced features resulting from the reaction tunneling are significantly
      diminished accordingly in the reactions of the deuterium atom and H(2)O or HOD,
      owing to the weaker tunneling capability of the reagent deuterium atom in the
      title reactions than the reagent hydrogen atom in other reactions. In the CS
      calculations, the resonance peaks persist in many partial waves but cannot
      survive the partial-wave summations. The cross sections for the D(') + H(2)O ->
      D(')OH + H and D(') + HOD -> D(')OD + H reactions are substantially larger than
      those for the D(') + HOD -> HOD(') + D reaction, indicating that the D(')/H
      exchange reactions are much more favored than the D(')/D exchange.

PMID- 22612090
TI  - A molecular H2 potential for heterogeneous simulations including polarization and
      many-body van der Waals interactions.
AB  - A highly accurate aniostropic intermolecular potential for diatomic hydrogen has
      been developed that is transferable for molecular modeling in heterogeneous
      systems. The potential surface is designed to be efficacious in modeling mixed
      sorbates in metal-organic materials that include sorption interactions with
      charged interfaces and open metal sites. The potential parameters are compatible
      for mixed simulations but still maintain high accuracy while deriving dispersion
      parameters from a proven polarizability model. The potential includes essential
      physical interactions including: short-range repulsions, dispersion, and
      permanent and induced electrostatics. Many-body polarization is introduced via a
      point-atomic polarizability model that is also extended to account for many-body
      van der Waals interactions in a consistent fashion. Permanent electrostatics are
      incorporated using point partial charges on atomic sites. However, contrary to
      expectation, the best potentials are obtained by permitting the charges to take
      on values that do not reproduce the first non-vanishing moment of the
      electrostatic potential surface, i.e., the quadrupole moment. Potential
      parameters are fit to match ab initio energies for a representative range of
      dimer geometries. The resulting potential is shown to be highly effective by
      comparing to electronic structure calculations for a thermal distribution of
      trimer geometries, and by reproducing experimental bulk pressure-density
      isotherms. The surface is shown to be superior to other similarly portable
      potential choices even in tests on homogeneous systems without strong polarizing
      fields. The present streamlined approach to developing such potentials allows for
      a simple adaptation to other molecules amenable to investigation by high-level
      electronic structure methods.

PMID- 22612091
TI  - Multielectron effects in high harmonic generation in N2 and benzene: simulation
      using a non-adiabatic quantum molecular dynamics approach for laser-molecule
      interactions.
AB  - A mixed quantum-classical approach is introduced which allows the dynamical
      response of molecules driven far from equilibrium to be modeled. This method is
      applied to the interaction of molecules with intense, short-duration laser
      pulses. The electronic response of the molecule is described using time-dependent
      density functional theory (TDDFT) and the resulting Kohn-Sham equations are
      solved numerically using finite difference techniques in conjunction with local
      and global adaptations of an underlying grid in curvilinear coordinates. Using
      this approach, simulations can be carried out for a wide range of molecules and
      both all-electron and pseudopotential calculations are possible. The approach is
      applied to the study of high harmonic generation in N(2) and benzene using
      linearly polarized laser pulses and, to the best of our knowledge, the results
      for benzene represent the first TDDFT calculations of high harmonic generation in
      benzene using linearly polarized laser pulses. For N(2) an enhancement of the cut
      off harmonics is observed whenever the laser polarization is aligned
      perpendicular to the molecular axis. This enhancement is attributed to the
      symmetry properties of the Kohn-Sham orbital that responds predominantly to the
      pulse. In benzene we predict that a suppression in the cut-off harmonics occurs
      whenever the laser polarization is aligned parallel to the molecular plane. We
      attribute this suppression to the symmetry-induced response of the highest
      occupied molecular orbital.

PMID- 22612092
TI  - Photoelectron spectroscopy and theoretical studies of UF5(-) and UF6(-).
AB  - The UF(5)(-) and UF(6)(-) anions are produced using electrospray ionization and
      investigated by photoelectron spectroscopy and relativistic quantum chemistry. An
      extensive vibrational progression is observed in the spectra of UF(5)(-),
      indicating significant geometry changes between the anion and neutral ground
      state. Franck-Condon factor simulations of the observed vibrational progression
      yield an adiabatic electron detachment energy of 3.82 +/- 0.05 eV for UF(5)(-).
      Relativistic quantum calculations using density functional and ab initio theories
      are performed on UF(5)(-) and UF(6)(-) and their neutrals. The ground states of
      UF(5)(-) and UF(5) are found to have C(4v) symmetry, but with a large U-F bond
      length change. The ground state of UF(5)(-) is a triplet state ((3)B(2)) with the
      two 5f electrons occupying a 5f(z3)-based 8a(1) highest occupied molecular
      orbital (HOMO) and the 5f(xyz)-based 2b(2) HOMO-1 orbital. The detachment cross
      section from the 5f(xyz) orbital is observed to be extremely small and the
      detachment transition from the 2b(2) orbital is more than ten times weaker than
      that from the 8a(1) orbital at the photon energies available. The UF(6)(-) anion
      is found to be octahedral, similar to neutral UF(6) with the extra electron
      occupying the 5f(xyz)-based a(2u) orbital. Surprisingly, no photoelectron
      spectrum could be observed for UF(6)(-) due to the extremely low detachment cross
      section from the 5f(xyz)-based HOMO of UF(6)(-).

PMID- 22612093
TI  - Evolution of superhalogen properties in PtCl(n) clusters.
AB  - We have systematically calculated the ground state geometries, relative
      stability, electronic structure, and spectroscopic properties of PtCl(n) (n = 1
      7) clusters. The bonding in these clusters is dominated by covalent interaction.
      In neutral clusters, chlorine atoms are chemically bound to Pt up to n = 5.
      However, in neutral PtCl(6) and PtCl(7) clusters, two of the chlorine atoms bind
      molecularly while the remaining bind as individual atoms. In the negative ions,
      this happens only in the case of PtCl(7) cluster. The geometries of both neutral
      and anionic clusters can be considered as fragments of an octahedron and are
      attributed to the stabilization associated with splitting of partially filled d
      orbitals under the chloride ligand field. The electron affinity of PtCl(n)
      clusters rises steadily with n, reaching a maximum value of 5.81 eV in PtCl(5).
      PtCl(n) clusters with n >= 3 are all superhalogens with electron affinities
      larger than that of chlorine. The accuracy of our results has been verified by
      carrying out photoelectron spectroscopy experiments on PtCl(n)(-) anion clusters.

PMID- 22612094
TI  - Rovibrational dynamics of the strontium molecule in the A(1)Sigma(u)+, c(3)Pi(u),
      and a(3)Sigma(u)+ manifold from state-of-the-art ab initio calculations.
AB  - State-of-the-art ab initio techniques have been applied to compute the potential
      energy curves for the electronic states in the A(1)Sigma(u)(+), c(3)Pi(u), and
      a(3)Sigma(u)(+) manifold of the strontium dimer, the spin-orbit and nonadiabatic
      coupling matrix elements between the states in the manifold, and the electric
      transition dipole moment from the ground X(1)Sigma(g)(+) to the nonrelativistic
      and relativistic states in the A+c+a manifold. The potential energy curves and
      transition moments were obtained with the linear response (equation of motion)
      coupled cluster method limited to single, double, and linear triple excitations
      for the potentials and limited to single and double excitations for the
      transition moments. The spin-orbit and nonadiabatic coupling matrix elements were
      computed with the multireference configuration interaction method limited to
      single and double excitations. Our results for the nonrelativistic and
      relativistic (spin-orbit coupled) potentials deviate substantially from recent ab
      initio calculations. The potential energy curve for the spectroscopically active
      (1)0(u)(+) state is in quantitative agreement with the empirical potential fitted
      to high-resolution Fourier transform spectra [A. Stein, H. Knockel, and E.
      Tiemann, Eur. Phys. J. D 64, 227 (2011)]. The computed ab initio points were
      fitted to physically sound analytical expressions, and used in converged coupled
      channel calculations of the rovibrational energy levels in the A+c+a manifold and
      line strengths for the A(1)Sigma(u)(+)<-X(1)Sigma(g (+) transitions. Positions
      and lifetimes of quasi-bound Feshbach resonances lying above the (1)S(0) +
      (3)P(1) dissociation limit were also obtained. Our results reproduce
      (semi)quantitatively the experimental data observed thus far. Predictions for on
      going and future experiments are also reported.

PMID- 22612095
TI  - The electronic spectrum of Si3 I: triplet D(3h) system.
AB  - We report the measurement of a jet-cooled electronic spectrum of the silicon
      trimer. Si(3) was produced in a pulsed discharge of silane in argon, and the
      excitation spectrum examined in the 18 000-20 800 cm(-1) region. A combination of
      resonant two-color two-photon ionization (R2C2PI) time-of-flight mass
      spectroscopy, laser-induced fluorescence/dispersed fluorescence, and equation-of
      motion coupled-cluster calculations have been used to establish that the observed
      spectrum is dominated by the 1(3)A(1)" - a (3)A(2)' transition of the D(3h)
      isomer. The spectrum has an origin transition at 18,600 +/- 4 cm(-1) and a short
      progression in the symmetric stretch with a frequency of ~445 cm(-1), in good
      agreement with a predicted vertical transition energy of 2.34 eV for excitation
      to the 1(3)A(1)" state, which has a calculated symmetric stretching frequency of
      480 cm(-1). In addition, a ~505 cm(-1) ground state vibrational frequency
      determined from sequence bands and dispersed fluorescence is in agreement with an
      earlier zero-electron kinetic energy study of the lowest D(3h) state and with
      theory. A weaker, overlapping band system with a ~360 cm(-1) progression,
      observed in the same mass channel (m/z = 84) by R2C2PI but under different
      discharge conditions, is thought to be due to transitions from the (more
      complicated) singlet C(2v) ground state ((1)A(1)) state of Si(3). Evidence of
      emission to this latter state in the triplet dispersed fluorescence spectra
      suggests extensive mixing in the excited triplet and singlet manifolds. Prospects
      for further spectroscopic characterization of the singlet system and direct
      measurement of the energy separation between the lowest singlet and triplet
      states are discussed.

PMID- 22612096
TI  - Laser-induced enhancement of tunneling in NHD2.
AB  - We apply and explore techniques aiming at enhancing the tunneling by laser
      fields, originally developed for a one-dimensional model, to a complete six
      dimensional vibrational model of the inversion motion in NHD(2). The
      computational study is performed with the multi-configuration time-dependent
      Hartree method. Assuming an ideal three-dimensional alignment we obtain a driven
      tunneling time twenty times smaller than the natural one, in rather good
      agreement with an oversimplified three-state model. In the case of one
      dimensional alignment, a linearly polarized field leads to a poor enhancement of
      the tunneling probability, after averaging over the rotation about the alignment
      axis, whereas a circularly polarized field improves the rotationally averaged
      tunneling probability at the end of the pulse.

PMID- 22612097
TI  - Resonant inelastic x-ray scattering of CeB6 at the Ce L(1)- and L(3)-edges.
AB  - We report a resonant inelastic x-ray scattering (RIXS) study of crystalline
      CeB(6). Ce L(alpha1,2) RIXS was measured with excitation energies resonant with
      the Ce L(3)-edge. A lifetime-broadening suppressed x-ray absorption near-edge
      structure (LBS-XANES), which successfully reproduced the L(alpha1,2) RIXS spectra
      over wide ranges of excitation and emission energies, was simulated using the SIM
      RIXS program. A pre-edge structure in the LBS-XANES can be resolved, and many
      body effects were suggested in the L(alpha1,2) RIXS around the Ce L(3)-edge
      energy. No convincing signs of Ce (II) or Ce (IV) states were observed in the LBS
      XANES. Ce L(gamma4) RIXS was measured at 302 K and 28 K with excitation energies
      across the Ce L(1)-edge. The interactions of p-valence electrons between Ce and
      B(6) were found to be considerably small, regardless of temperature. Thus, the
      electronic state of CeB(6) was concluded to be suitably described as a nominally
      Ce(4f(1))(3+)(e(-))(B(6))(2-) system with some hybridization among all valence
      orbitals of Ce and B.

PMID- 22612098
TI  - Theory and simulation of anisotropic pair correlations in ferrofluids in magnetic
      fields.
AB  - Anisotropic pair correlations in ferrofluids exposed to magnetic fields are
      studied using a combination of statistical-mechanical theory and computer
      simulations. A simple dipolar hard-sphere model of the magnetic colloidal
      particles is studied in detail. A virial-expansion theory is constructed for the
      pair distribution function (PDF) which depends not only on the length of the pair
      separation vector, but also on its orientation with respect to the field. A
      detailed comparison is made between the theoretical predictions and accurate
      simulation data, and it is found that the theory works well for realistic values
      of the dipolar coupling constant (lambda = 1), volume fraction (phi <= 0.1), and
      magnetic field strength. The structure factor is computed for wavevectors either
      parallel or perpendicular to the field. The comparison between theory and
      simulation is generally very good with realistic ferrofluid parameters. For both
      the PDF and the structure factor, there are some deviations between theory and
      simulation at uncommonly high dipolar coupling constants, and with very strong
      magnetic fields. In particular, the theory is less successful at predicting the
      behavior of the structure factors at very low wavevectors, and perpendicular
      Gaussian density fluctuations arising from strongly correlated pairs of magnetic
      particles. Overall, though, the theory provides reliable predictions for the
      nature and degree of pair correlations in ferrofluids in magnetic fields, and
      hence should be of use in the design of functional magnetic materials.

PMID- 22612099
TI  - Excess protons in water-acetone mixtures.
AB  - Using molecular dynamics experiments, we analyze equilibrium and dynamical
      characteristics related to the solvation of excess protons in water-acetone
      mixtures. Our approach is based on the implementation of an extended valence-bond
      Hamiltonian, which incorporates translocation of the excess charge between
      neighboring water molecules. Different mixtures have been analyzed, starting from
      the pure water case down to solutions with a water molar fraction x(w) = 0.25. In
      all cases, we have verified that the structure of the first solvation shell of
      the H(3)O(+) moiety remains practically unchanged, compared to the one observed
      in pure water. This shell is composed by three water molecules acting as hydrogen
      bond acceptors, with no evidence of hydrogen bond donor-like connectivity.
      Moreover, the increment in the acetone concentration leads to a gradual
      stabilization of Eigen-like [H(3)O[middle dot](H(2)O)(3)](+) configurations, in
      detriment of Zundel-like [H[middle dot](H(2)O)(2)](+) ones. Rates of proton
      transfer and proton diffusion coefficients have been recorded at various water
      acetone relative concentrations. In both cases, we have found a transition
      region, in the vicinity of x(w) ~ 0.8, where the concentration dependences of the
      two magnitudes change at a quantitative level. A crude estimate shows that, at
      this tagged concentration, the volumes "occupied" by the two solvents become
      comparable. The origins of this transition separating water-rich from acetone
      rich realms is rationalized in terms of modifications operated in the nearby,
      second solvation shell, which in the latter solutions, normally includes at
      least, one acetone molecule. Our results would suggest that one possible
      mechanism controlling the proton transfer in acetone-rich solutions is the
      exchange of one of these tagged acetone molecules, by nearby water ones. This
      exchange would give rise to Zundel-like structures, exhibiting a symmetric, first
      solvation shell composed exclusively by water molecules, and would facilitate the
      transfer between neighboring water molecules along the resonant complex.

PMID- 22612100
TI  - Influence of anion on the quadratic nonlinearity and depolarization ratios of
      scattered second harmonic light from cation-pi complexes.
AB  - We have investigated quadratic nonlinearity (beta(HRS)) and linear and circular
      depolarization ratios (D and D('), respectively) of a series of 1:1 complexes of
      tropyliumtetrafluoroborate as a cation and methyl-substituted benzenes as pi
      donors by making polarization resolved hyper-Rayleigh scattering measurements in
      solution. The measured D and D(') values are much lower than the values expected
      from a typical sandwich or a T-shaped geometry of a complex. In the cation-pi
      complexes studied here, the D value varies from 1.36 to 1.46 and D(') from 1.62
      to 1.72 depending on the number of methyl substitutions on the benzene ring. In
      order to probe it further, beta, D and D(') were computed using the Zerner
      intermediate neglect of differential overlap-correction vector self-consistent
      reaction field technique including single and double configuration interactions
      in the absence and presence of BF(4) (-) anion. In the absence of the anion, the
      calculated value of D varies from 4.20 to 4.60 and that of D(') from 2.45 to 2.72
      which disagree with experimental values. However, by arranging three cation-pi
      BF(4)(-) complexes in a trigonal symmetry, the computed values are brought to
      agreement with experiments. When such an arrangement was not considered, the
      calculated beta values were lower than the experimental values by more than a
      factor of two. This unprecedented influence of the otherwise "unimportant" anion
      in solution on the beta value and depolarization ratios of these cation-pi
      complexes is highlighted and emphasized in this paper.

PMID- 22612101
TI  - Molecular dynamics of excited state intramolecular proton transfer: 3
      hydroxyflavone in solution.
AB  - The ultrafast enol-keto photoisomerization in the lowest singlet excited state of
      3-hydroxyflavone is investigated using classical molecular dynamics in
      conjunction with empirical valence bond (EVB) potentials for the description of
      intramolecular interactions, and a molecular mechanics and variable partial
      charge model, dependent on transferring proton position, for the description of
      solute-solvent interactions. A parallel multi-level genetic program was used to
      accurately fit the EVB potential energy surfaces to high level ab initio data. We
      have studied the excited state intramolecular proton transfer (ESIPT) reaction in
      three different solvent environments: methylcyclohexane, acetonitrile, and
      methanol. The effects of the environment on the proton transfer time and the
      underlying mechanisms responsible for the varied time scales of the ESIPT
      reaction rates are analyzed. We find that simulations with our EVB potential
      energy surfaces accurately reproduce experimentally determined reaction rates,
      fluorescence spectra, and vibrational frequency spectra in all three solvents.
      Furthermore, we find that the ultrafast ESIPT process results from a combination
      of ballistic transfer, and intramolecular vibrational redistribution, which leads
      to the excitation of a set of low frequency promoting vibrational modes. From
      this set of promoting modes, we find that an O-O in plane bend and a C-H out of
      plane bend are present in all three solvents, indicating that they are
      fundamental to the ultrafast proton transfer. Analysis of the slow proton
      transfer trajectories reveals a solvent mediated proton transfer mechanism, which
      is diffusion limited.

PMID- 22612102
TI  - Molecular dynamics simulation studies of the influence of imidazolium structure
      on the properties of imidazolium/azide ionic liquids.
AB  - Atomistic molecular dynamics simulations were performed on 1-butyl-3-methyl
      imidazolium azide [bmim][N(3)], 1-butyl-2,3-dimethylimidazolium azide
      [bmmim][N(3)], and 1-butynyl-3-methyl-imidazolium azide [bumim][N(3)] ionic
      liquids. The many-body polarizable APPLE&P force field was augmented with
      parameters for the azide anion and the bumim cation. Good agreement between the
      experimentally determined and simulated crystal structure of [bumim][N(3)] as
      well as the liquid-state density and ionic conductivity of [bmmim][N(3)] were
      found. Methylation of bmim (yielding bmmim) resulted in dramatic changes in ion
      structuring in the liquid and slowing of ion motion. Conversely, replacing the
      butyl group of bmim with the smaller 2-butynyl group resulted in an increase of
      ion dynamics.

PMID- 22612103
TI  - Relaxation and jump dynamics of water at the mica interface.
AB  - The orientational relaxation dynamics of water confined between mica surfaces is
      investigated using molecular dynamics simulations. The study illustrates the wide
      heterogeneity that exists in the dynamics of water adjacent to a strongly
      hydrophilic surface such as mica. Analysis of the survival probabilities in
      different layers is carried out by normalizing the corresponding relaxation times
      with bulk water layers of similar thickness. A 10-fold increase in the survival
      times is observed for water directly in contact with the mica surface and a non
      monotonic variation in the survival times is observed moving away from the mica
      surface to the bulk-like interior. The orientational relaxation time is highest
      for water in the contact layer, decreasing monotonically away from the surface.
      In all cases the ratio of the relaxation times of the 1st and 2nd rank Legendre
      polynomials of the HH bond vector is found to lie between 1.5 and 1.9 indicating
      that the reorientational relaxation in the different water layers is governed by
      jump dynamics. The orientational dynamics of water in the contact layer is
      particularly novel and is found to undergo distinct two-dimensional hydrogen bond
      jump reorientational dynamics with an average waiting time of 4.97 ps. The
      waiting time distribution is found to possess a long tail extending beyond 15 ps.
      Unlike previously observed jump dynamics in bulk water and other surfaces, jump
      events in the mica contact layer occur between hydrogen bonds formed by the water
      molecule and acceptor oxygens on the mica surface. Despite slowing down of the
      water orientational relaxation near the surface, life-times of water in the
      hydration shell of the K(+) ion are comparable to that observed in bulk salt
      solutions.

PMID- 22612104
TI  - Molecular modification of coumarin dyes for more efficient dye sensitized solar
      cells.
AB  - In this work, new coumarin based dyes for dye sensitized solar cells (DSSC) have
      been designed by introducing several substituent groups in different positions of
      the NKX-2311 structure. Two types of substitutions have been considered: the
      introduction of three electron-donating groups (-OH, -NH(2), and -OCH(3)) and two
      different substituents with steric effect: -CH(2)-CH(2)-CH(2)- and -CH(2)-HC=CH-.
      The electronic absorption spectra (position and width of the first band and
      absorption threshold) and the position of the LUMO level related to the
      conduction band have been used as theoretical criteria to evaluate the efficiency
      of the new dyes. The introduction of a -NH(2) group produces a redshift of the
      absorption maximum position and the absorption threshold, which could improve the
      cell efficiency. In contrast, the introduction of -CH(2)-CH(2)-CH(2)- does not
      modify significantly the electronic structure of NKX-2311, but it might prevent
      aggregation. Finally, -CH(2)-HC=CH- produces important changes both in the
      electronic spectrum and in the electronic structure of the dye, and it would be
      expected as an improvement of cell efficiency for these dyes.

PMID- 22612105
TI  - Defect topologies in a nematic liquid crystal near a patchy colloid.
AB  - Using isothermal-isobaric Monte Carlo simulations we investigate defect
      topologies due to a spherical colloidal particle immersed in a nematic liquid
      crystal. Defects arise because of the competition between the preferential
      orientation at the colloid's surface and the far-field director n(0). Considering
      a chemically homogeneous colloid as a special case we observe the well-known
      surface and saturn ring defect topologies for weak and strong perpendicular
      anchoring, respectively; for homogeneous, strong parallel anchoring we find a
      boojum defect topology that has been seen experimentally [see P. Poulin and D. A.
      Weitz, Phys. Rev. E 57, 626 (1998)] but not in computer simulations. We also
      consider a heterogeneous, patchy colloid where the liquid-crystal molecules
      anchor either preferentially planar or perpendicular at the surface of the
      colloid. For a patchy colloid we observe a boojum ring defect topology in
      agreement with recent experimental studies [see M. Conradi, M. Ravnik, M. Bele,
      M. Zorko, S. Zumer, and I. Musevic, Soft Matter 5, 3905 (2009)]. We also observe
      two other novel defect topologies that have not been reported thus far neither
      experimentally nor theoretically.

PMID- 22612106
TI  - A surface enhanced Raman spectroscopy study of aminothiophenol and
      aminothiophenol-C60 self-assembled monolayers: evolution of Raman modes with
      experimental parameters.
AB  - P-aminothiophenol (PATP) is a well-known molecule for the preparation of self
      assembled monolayers on gold via its thiol functional group. After adsorption, it
      has been demonstrated that this molecule is anchored to gold through its thiol
      group, and standing nearly upright at the surface with the amino functional group
      on top. This molecule has been extensively studied by surface enhanced Raman
      spectroscopy but its exact SERS spectrum remains unclear. Here, we demonstrate
      that it can be strongly affected by at least two experimental parameters: laser
      power and layer density. Those features are discussed in terms of a dimerization
      of the PATP molecules. The free amino group affords the adsorption of other
      molecules such as C(60). In this case, a complex multilayer system is formed and
      the question of its precise characterisation remains a key point. In this
      article, we demonstrate that surface enhanced Raman spectroscopy combined with x
      ray photoelectron spectroscopy can bring very important information about the
      organization of such a self-assembled multilayer on gold. In our study, the
      strong evolution of Raman modes after C(60) adsorption suggests a change in the
      organization of aminothiophenol molecules during C(60) adsorption. These changes,
      also observed when the aminothiophenol layer is annealed in toluene, do not
      prevent the adsorption of C(60) molecules.

PMID- 22612107
TI  - Ab initio-based double many-body expansion potential energy surface for the first
      excited triplet state of the ammonia molecule.
AB  - A global single-sheeted double many-body expansion potential energy surface is
      reported for the first excited triplet state of NH(3). It employs an approximate
      cluster expansion of the molecular potential that utilizes previously reported
      functions of the same family for the triatomic fragments. Four-body energy terms
      have been calibrated from extensive accurate ab initio data so as to reproduce
      the main features of the title system. A new switching function formalism has
      been reported to approximate the true multisheeted nature of NH(3)((3)A(2) (''))
      potential energy surface, thus allowing the correct behavior at the
      NH(2)((2)A(")) + H((2)S) and NH(2)((4)A(")) + H((2)S) dissociation limits. The
      resulting fully six-dimensional potential energy function reproduces the correct
      symmetry under the permutation of identical atoms, and predicts the correct
      behavior at all dissociation channels while providing a realistic representation
      at all interatomic separations. The major attributes of the NH(3) double many
      body expansion potential energy surface have also been characterized, and found
      to be in good agreement, both with the calculated ones from the raw ab initio
      energies and the theoretical results available in the literature.

PMID- 22612108
TI  - Anisotropic flow in striped superhydrophobic channels.
AB  - We report results of dissipative particle dynamics simulations and develop a semi
      analytical theory of an anisotropic flow in a parallel-plate channel with two
      superhydrophobic striped walls. Our approach is valid for any local slip at the
      gas sectors and an arbitrary distance between the plates, ranging from a thick to
      a thin channel. It allows us to optimize area fractions, slip lengths, channel
      thickness, and texture orientation to maximize a transverse flow. Our results may
      be useful for extracting effective slip tensors from global measurements, such as
      the permeability of a channel, in experiments or simulations, and may also find
      applications in passive microfluidic mixing.

PMID- 22612109
TI  - Effects of the covalent linker groups on the spin transport properties of single
      nickelocene molecules attached to single-walled carbon nanotubes.
AB  - The understanding of how the spin moment of a magnetic molecule transfers to a
      carbon nanotube, when the molecule is attached to it, is crucial for designing
      novel supramolecular spin devices. Here we explore such an issue by modeling the
      spin transport of a single-walled carbon nanotube grafted with one nickelocene
      molecule. In particular we investigate how the electron transport becomes spin
      polarized depending on the specific linking group bonding nickelocene to the
      nanotube. We consider as linkers both aziridine and pyrrolidine rings and the
      amide group. Our calculations show that, at variance with aziridine, both
      pyrrolidine and amide, do alter the sp(2) character of the binding site of the
      nanotube and thus affect the transmission around the Fermi level. However, only
      aziridine allows transferring the spin polarization of the nickelocene to the
      nanotube, whose conductance at the Fermi level becomes spin-polarized. This
      suggests the superiority of aziridine as a linker for grafting magnetic molecules
      onto carbon nanotubes with efficient spin filtering functionality.

PMID- 22612110
TI  - Semiflexible polymers grafted to a solid planar substrate: changing the structure
      from polymer brush to "polymer bristle".
AB  - Monte Carlo simulations are presented for a coarse-grained model of polymer
      brushes with polymers having a varying degree of stiffness. Both linear chains
      and ring polymers grafted to a flat structureless non-adsorbing substrate surface
      are considered. Applying good solvent conditions, it is shown that with growing
      polymer stiffness the brush height increases significantly. The monomer density
      profiles for the case of ring polymers (chain length N(R) = 64) are very similar
      to the case of corresponding linear chains (N(L) = 32, grafting density larger by
      a factor of two) in the case of flexible polymers, while slight differences
      appear with increasing stiffness. Evidence is obtained that the chain dynamics in
      brushes is slowed down dramatically with increasing stiffness. Very short stiff
      rings (N(R) <= 16) behave like disks, grafted to the substrate such that the
      vector, perpendicular to the disk plane, is oriented parallel to the substrate
      surface. It is suggested that such systems can undergo phase transitions to
      states with liquid crystalline order.

PMID- 22612111
TI  - Lattice cluster theory of associating telechelic polymers. III. Order parameter
      and average degree of self-assembly, transition temperature, and specific heat.
AB  - The lattice cluster theory of strongly interacting, structured polymer fluids is
      applied to determine the thermodynamic properties of solutions of telechelic
      polymers that may associate through bifunctional end groups. Hence, this model
      represents a significant albeit natural extension of a diverse array of prior
      popular equilibrium polymerization models in which structureless "bead" monomers
      associate into chain-like clusters under equilibrium conditions. In particular,
      the thermodynamic description of the self-assembly of linear telechelic chains in
      small molecule solvents (initiated in Paper II) is systematically extended
      through calculations of the order parameter Phi and average degree <N> of self
      assembly, the self-assembly transition temperature T(p), and the specific heat
      C(V) of solutions of telechelic molecules. Special focus is placed on examining
      how molecular and thermodynamic parameters, such as the solution composition phi,
      temperature T, microscopic interaction energies (epsilon(s) and epsilon), and
      length M of individual telechelic chains, influence the computed thermodynamic
      quantities that are commonly used to characterize self-assembling systems.

PMID- 22612112
TI  - Lattice cluster theory of associating polymers. IV. Phase behavior of telechelic
      polymer solutions.
AB  - The newly developed lattice cluster theory (in Paper I) for the thermodynamics of
      solutions of telechelic polymers is used to examine the phase behavior of these
      complex fluids when effective polymer-solvent interactions are unfavorable. The
      telechelics are modeled as linear, fully flexible, polymer chains with mono
      functional stickers at the two chain ends, and these chains are assumed to self
      assemble upon cooling. Phase separation is generated through the interplay of
      self-assembly and polymer/solvent interactions that leads to an upper critical
      solution temperature phase separation. The variations of the boundaries for phase
      stability and the critical temperature and composition are analyzed in detail as
      functions of the number M of united atom groups in a telechelic chain and the
      microscopic nearest neighbor interaction energy epsilon(s) driving the self
      assembly. The coupling between self-assembly and unfavorable polymer/solvent
      interactions produces a wide variety of nontrivial patterns of phase behavior,
      including an enhancement of miscibility accompanying the increase of the molar
      mass of the telechelics under certain circumstances. Special attention is devoted
      to understanding this unusual trend in miscibility.

PMID- 22612114
TI  - Comment on "Revised electron affinity of SF6 from kinetic data" [J. Chem. Phys.
      136, 121102 (2012)].
AB  - The adiabatic electron affinity (AEA) of SF(6) has been calculated near the
      relativistic CCSDT(Q) basis set limit. Our best theoretical value (1.0340 +/-
      0.03 eV) is in excellent agreement with the recently revised experimental value
      of 1.03 +/- 0.05 eV reported by Troe et al. [J. Chem. Phys. 136, 121102 (2012)].
      While our best nonrelativistic, clamped-nuclei, valence CCSD(T) basis set limit
      value of 0.9058 eV is in good accord with the previously reported CCSD(T)/CBS
      values, to obtain an accurate AEA, several additional contributions need to be
      taken into account. The most important one is scalar-relativistic effects (0.0839
      eV), followed by inner-shell correlation (0.0216 eV) and post-CCSD(T) correlation
      effects (0.0248 eV), the latter almost entirely due to connected quadruple
      excitations. The diagonal Born-Oppenheimer correction is an order of magnitude
      less important at -0.0022 eV.

PMID- 22612115
TI  - Retraction: "Low energy collisions of CN(X2)Sigma+) with He in magnetic fields"
      [J. Chem. Phys. 136, 054302 (2012)].

PMID- 22612113
TI  - Elastic network normal modes provide a basis for protein structure refinement.
AB  - It is well recognized that thermal motions of atoms in the protein native state,
      the fluctuations about the minimum of the global free energy, are well reproduced
      by the simple elastic network models (ENMs) such as the anisotropic network model
      (ANM). Elastic network models represent protein dynamics as vibrations of a
      network of nodes (usually represented by positions of the heavy atoms or by the
      C(alpha) atoms only for coarse-grained representations) in which the spatially
      close nodes are connected by harmonic springs. These models provide a reliable
      representation of the fluctuational dynamics of proteins and RNA, and explain
      various conformational changes in protein structures including those important
      for ligand binding. In the present paper, we study the problem of protein
      structure refinement by analyzing thermal motions of proteins in non-native
      states. We represent the conformational space close to the native state by a set
      of decoys generated by the I-TASSER protein structure prediction server utilizing
      template-free modeling. The protein substates are selected by hierarchical
      structure clustering. The main finding is that thermal motions for some
      substates, overlap significantly with the deformations necessary to reach the
      native state. Additionally, more mobile residues yield higher overlaps with the
      required deformations than do the less mobile ones. These findings suggest that
      structural refinement of poorly resolved protein models can be significantly
      enhanced by reduction of the conformational space to the motions imposed by the
      dominant normal modes.

PMID- 22612116
TI  - Potential clinical impact of three-dimensional visualization for fluorescent in
      situ hybridization image analysis.
AB  - Chromosomal translocation is strong indication of cancers. Fluorescent in situ
      hybridization (FISH) can effectively detect this translocation and achieve high
      accuracy in disease diagnosis and prognosis assessment. For this purpose, whole
      chromosome paint probes are utilized to image the configuration of DNA fragments.
      Although two-dimensional (2-D) microscopic images are typically used in FISH
      signal analysis, we present a case where the translocation occurs in the depth
      direction where two probed FISH signals are overlapped in the projected image
      plane. Thus, the translocation cannot be identified. However, when imaging the
      whole specimen with a confocal microscope at 27 focal planes with 0.5-MUm step
      interval, the translocation can be clearly identified due to the free rotation
      capability by the three-dimensional (3-D) visualization. Such a translocation
      detection error of using 2-D images might be critical in detecting and diagnosing
      early or subtle disease cases where detecting a small number of abnormal cells
      can make diagnostic difference. Hence, the underlying implication of this report
      suggests that utilizing 3-D visualization may improve the overall accuracy of
      FISH analysis for some clinical cases. However, the clinical efficiency and cost
      of using 3-D versus 2-D imaging methods are also to be assessed carefully.

PMID- 22612118
TI  - Real time processing of Fourier domain optical coherence tomography with fixed
      pattern noise removal by partial median subtraction using a graphics processing
      unit.
AB  - The author presents a graphics processing unit (GPU) programming for real-time
      Fourier domain optical coherence tomography (FD-OCT) with fixed-pattern noise
      removal by subtracting mean and median. In general, the fixed-pattern noise can
      be removed by the averaged spectrum from the many spectra of an actual
      measurement. However, a mean-spectrum results in artifacts as residual lateral
      lines caused by a small number of high-reflective points on a sample surface.
      These artifacts can be eliminated from OCT images by using medians instead of
      means. However, median calculations that are based on a sorting algorithm can
      generate a large amount of computation time. With the developed GPU programming,
      highly reflective surface regions were obtained by calculating the standard
      deviation of the Fourier transformed data in the lateral direction. The medians
      and means were then subtracted at the observed regions and other regions, such as
      backgrounds. When the median calculation was less than 256 positions out of a
      total 512 depths in an OCT image with 1024 A-lines, the GPU processing rate was
      faster than that of the line scan camera (46.9 kHz). Therefore, processed OCT
      images can be displayed in real-time using partial medians.

PMID- 22612119
TI  - Optical vortex behavior in dynamic speckle fields.
AB  - The dynamic behavior of phase singularities, or optical vortices, in the pseudo
      phase representation of dynamic speckle patterns is investigated. Sequences of
      band-limited, dynamic speckle patterns with predetermined Gaussian decorrelation
      behavior were generated, and the pseudo-phase realizations of the individual
      speckle patterns were calculated via a two-dimensional Hilbert transform
      algorithm. Singular points in the pseudo-phase representation are identified by
      calculating the local topological charge as determined by convolution of the
      pseudo-phase representations with a series of 2*2 nabla filters. The spatial
      locations of the phase singularities are tracked over all frames of the speckle
      sequences, and recorded in three-dimensional space (x,y,f), where f is frame
      number in the sequence. The behavior of the phase singularities traces 'vortex
      trails' which are representative of the speckle dynamics. Slowly decorrelating
      speckle patterns results in long, relatively straight vortex trails, while
      rapidly decorrelating speckle patterns results in tortuous, relatively short
      vortex trails. Optical vortex analysis such as described herein can be used as a
      descriptor of biological activity, flow, and motion.

PMID- 22612117
TI  - Label free in vivo laser speckle imaging of blood and lymph vessels.
AB  - The peripheral lymphatic vascular system is a part of the immune body system
      comprising a complex network of lymph vessels and nodes that are flowing lymph
      toward the heart. Traditionally the imaging of lymphatic vessels is based on the
      conventional imaging modalities utilizing contrast fluorescence materials. Given
      the important role of the lymphatic system there is a critical need for the
      development of noninvasive imaging technologies for functional quantitative
      diagnosis of the lymph vessels and lymph flow without using foreign chemicals. We
      report a label free methodology for noninvasive in vivo imaging of blood and
      lymph vessels, using long-exposure laser speckle imaging approach. This approach
      entails great promise in the noninvasive studies of tissues blood and lymph
      vessels distribution in vivo.

PMID- 22612120
TI  - Simultaneous imaging of multiple focal planes for three-dimensional microscopy
      using ultra-high-speed adaptive optics.
AB  - Traditional white-light and fluorescent imaging techniques provide powerful
      methods to extract high-resolution information from two-dimensional (2-D)
      sections, but to retrieve information from a three-dimensional (3-D) volume they
      require relatively slow scanning methods that result in increased acquisition
      time. Using an ultra-high speed liquid lens, we circumvent this problem by
      simultaneously acquiring images from multiple focal planes. We demonstrate this
      method by imaging microparticles and cells flowing in 3-D microfluidic channels.

PMID- 22612121
TI  - Whole-body ring-shaped confocal photoacoustic computed tomography of small
      animals in vivo.
AB  - We report a novel small-animal whole-body imaging system called ring-shaped
      confocal photoacoustic computed tomography (RC-PACT). RC-PACT is based on a
      confocal design of free-space ring-shaped light illumination and 512-element full
      ring ultrasonic array signal detection. The free-space light illumination
      maximizes the light delivery efficiency, and the full-ring signal detection
      ensures a full two-dimensional view aperture for accurate image reconstruction.
      Using cylindrically focused array elements, RC-PACT can image a thin cross
      section with 0.10 to 0.25 mm in-plane resolutions and 1.6  s/frame acquisition
      time. By translating the mouse along the elevational direction, RC-PACT provides
      a series of cross-sectional images of the brain, liver, kidneys, and bladder.

PMID- 22612122
TI  - Geometry-invariant gradient refractive index lens: analytical ray tracing.
AB  - A new class of gradient refractive index (GRIN) lens is introduced and analyzed.
      The interior iso-indicial contours mimic the external shape of the lens, which
      leads to an invariant geometry of the GRIN structure. The lens model employs a
      conventional surface representation using a coincoid of revolution with a higher
      order aspheric term. This model has a unique feature, namely, it allows
      analytical paraxial ray tracing. The height and the angle of an arbitrary
      incident ray can be found inside the lens in a closed-form expression, which is
      used to calculate the main optical characteristics of the lens, including the
      optical power and third-order monochromatic aberration coefficients. Moreover,
      due to strong coupling of the external surface shape to the GRIN structure, the
      proposed GRIN lens is well suited for studying accommodation mechanism in the
      eye. To show the power of the model, several examples are given emphasizing the
      usefulness of the analytical solution. The presented geometry-invariant GRIN lens
      can be used for modeling and reconstructing the crystalline lens of the human eye
      and other types of eyes featuring a GRIN lens.

PMID- 22612123
TI  - Validity of a theoretical model to examine blood oxygenation dependent
      optoacoustics.
AB  - A theoretical model investigating the dependence of optoacoustic (OA) signal on
      blood oxygen saturation (SO(2)) is discussed. The derivations for the
      nonbandlimited and bandlimited OA signals from many red blood cells (RBCs) are
      presented. The OA field generated by many RBCs was obtained by summing the OA
      field emitted by each RBC approximated as a fluid sphere. A Monte Carlo technique
      was employed generating the spatial organizations of RBCs in two-dimensional. The
      RBCs were assumed to have the same SO(2) level in a simulated configuration. The
      fractional number of oxyhemoglobin molecules, confined in a cell, determined the
      cellular SO(2) and also defined the blood SO(2). For the nonbandlimited case, the
      OA signal amplitude decreased and increased linearly with blood SO(2) when
      illuminated by 700 and 1000 nm radiations, respectively. The power spectra
      exhibited similar trends over the entire frequency range (MHz to GHz). For the
      bandlimited case, three acoustic receivers with 2, 10, and 50 MHz as the center
      frequencies were considered. The linear variations of the OA amplitude with blood
      SO(2) were also observed for each receiver at those laser sources. The good
      agreement between simulated and published experimental results validates the
      model qualitatively.

PMID- 22612124
TI  - In vivo fluorescence lifetime detection of an activatable probe in infarcted
      myocardium.
AB  - Activatable fluorescent molecular probes are predominantly nonfluorescent in
      their inactivated state due to intramolecular quenching, but increase
      fluorescence yield significantly after enzyme-mediated hydrolysis of peptides.
      Continuous wave in vivo detection of these protease-activatable fluorophores in
      the heart, however, is limited by the inability to differentiate between
      activated and nonactivated fractions of the probe and is frequently complicated
      by large background signal from probe accumulation in the liver. Using a
      cathepsin-activatable near-infrared probe (PGC-800), we demonstrate here that
      fluorescence lifetime (FL) significantly increases in infarcted murine myocardial
      tissue (0.67 ns) when compared with healthy myocardium (0.59 ns) after 24 h.
      Furthermore, we show that lifetime contrast can be used to distinguish in vivo
      cardiac fluorescence from background nonspecific liver signal. The results of
      this study show that lifetime contrast is a helpful addition to preclinical
      imaging of activatable fluorophores in the myocardium by reporting molecular
      activity in vivo due to changes in intramolecular quenching. This
      characterization of FL from activatable molecular probes will be helpful for
      advancing in vivo imaging of enzyme activity.

PMID- 22612125
TI  - Changes in diffusion path length with old age in diffuse optical tomography.
AB  - Diffuse, optical near infrared imaging is increasingly being used in various
      neurocognitive contexts where changes in optical signals are interpreted through
      activation maps. Statistical population comparison of different age or clinical
      groups rely on the relative homogeneous distribution of measurements across
      subjects in order to infer changes in brain function. In the context of an
      increasing use of diffuse optical imaging with older adult populations, changes
      in tissue properties and anatomy with age adds additional confounds. Few studies
      investigated these changes with age. Duncan et al. measured the so-called
      diffusion path length factor (DPF) in a large population but did not explore
      beyond the age of 51 after which physiological and anatomical changes are
      expected to occur [Pediatr. Res. 39(5), 889-894 (1996)]. With increasing interest
      in studying the geriatric population with optical imaging, we studied changes in
      tissue properties in young and old subjects using both magnetic resonance imaging
      (MRI)-guided Monte-Carlo simulations and time-domain diffuse optical imaging. Our
      results, measured in the frontal cortex, show changes in DPF that are smaller
      than previously measured by Duncan et al. in a younger population. The origin of
      these changes are studied using simulations and experimental measures.

PMID- 22612126
TI  - Comprehensive data visualization for high resolution endovascular carotid
      arterial wall imaging.
AB  - Carotid angioplasty and stenting is a minimally invasive endovascular procedure
      that may benefit from in vivo high resolution imaging for monitoring the physical
      placement of the stent and potential complications. The purpose of this pilot
      study was to evaluate the ability of optical coherence tomography to construct
      high resolution 2D and 3D images of stenting in porcine carotid artery. Four
      Yorkshire pigs were anaesthetized and catheterized. A state-of-the-art optical
      coherence tomography (OCT) system and an automated injector were used to obtain
      both healthy and stented porcine carotid artery images. Data obtained were then
      processed for visualization. The state-of-the-art OCT system was able to capture
      high resolution images of both healthy and stented carotid arteries. High quality
      3D images of healthy and stented carotid arteries were constructed, clearly
      depicting vessel wall morphological features, stent apposition and thrombus
      formation over the inserted stent. The results demonstrate that OCT can be used
      to generate high quality 3D images of carotid arterial stents for accurate
      diagnosis of stent apposition and complications under appropriate imaging
      conditions.

PMID- 22612127
TI  - Optimal ultraviolet wavelength for in vivo photoacoustic imaging of cell nuclei.
AB  - In order to image noninvasively cell nuclei in vivo without staining, we have
      developed ultraviolet photoacoustic microscopy (UV-PAM), in which ultraviolet
      light excites nucleic acids in cell nuclei to produce photoacoustic waves.
      Equipped with a tunable laser system, the UV-PAM was applied to in vivo imaging
      of cell nuclei in small animals. We found that 250 nm was the optimal wavelength
      for in vivo photoacoustic imaging of cell nuclei. The optimal wavelength enables
      UV-PAM to image cell nuclei using as little as 2 nJ laser pulse energy. Besides
      the optimal wavelength, application of a wavelength between 245 and 275 nm can
      produce in vivo images of cell nuclei with specific, positive, and high optical
      contrast.

PMID- 22612128
TI  - Load-dependent brain activation assessed by time-domain functional near-infrared
      spectroscopy during a working memory task with graded levels of difficulty.
AB  - We evaluated frontal brain activation during a mixed attentional/working memory
      task with graded levels of difficulty in a group of 19 healthy subjects, by means
      of time-domain functional near-infrared spectroscopy (fNIRS). Brain activation
      was assessed, and load-related oxy- and deoxy-hemoglobin changes were studied.
      Generalized linear model (GLM) was applied to the data to explore the metabolic
      processes occurring during the mental effort and, possibly, their involvement in
      short-term memorization. GLM was applied to the data twice: for modeling the task
      as a whole and for specifically investigating brain activation at each cognitive
      load. This twofold employment of GLM allowed (1) the extraction and isolation of
      different information from the same signals, obtained through the modeling of
      different cognitive categories (sustained attention and working memory), and (2)
      the evaluation of model fitness, by inspection and comparison of residuals (i.e.,
      unmodeled part of the signal) obtained in the two different cases. Results attest
      to the presence of a persistent attentional-related metabolic activity,
      superimposed to a task-related mnemonic contribution. Some hemispherical
      differences have also been highlighted frontally: deoxy-hemoglobin changes
      manifested a strong right lateralization, whereas modifications in oxy- and total
      hemoglobin showed a medial localization. The present work successfully explored
      the capability of fNIRS to detect the two neurophysiological categories under
      investigation and distinguish their activation patterns.

PMID- 22612129
TI  - Optimized off-axis cylindrical mirror-focused line-scanning system for optical
      coherence tomography imaging applications.
AB  - The parameters of an off-axis cylindrical mirror-focused line-scanning system
      were studied to optimize the flatness of the 2 mm scan field. The scanning system
      parameters included the beam size, the distance between the scanning and the
      focusing mirror, the angle between the incident beam and the reflected beam, the
      optical scan angle, and the effective focal length of the cylindrical mirror.
      Because of the off-axis line-scanning system configuration, the scanning could be
      carried out either in the tangential (Y-scan) or in the sagittal (X-scan) plane.
      A 53 nm spectral bandwidth light source was used to evaluate the imaging
      performance of the scanning system. Since reflective optics is employed in this
      work for focusing, the scanning system could be used with a higher spectral
      bandwidth light source for optical coherence tomography applications. The effect
      of the angle between of the incident and reflected beams, the distance between
      the mirrors, the focal length of the cylindrical mirror and the scanning
      directions, on the flatness of the scan field were studied. It was proved that
      the sagittal scanning is least sensitive to variations in scanning system
      parameters and thus provides maximum flexibility in design.

PMID- 22612130
TI  - Temperature-modulated fluorescence tomography based on both concentration and
      lifetime contrast.
AB  - It is challenging to image fluorescence objects with high spatial resolution in a
      highly scattering medium. Recently reported temperature-sensitive indocyanine
      green-loaded pluronic nanocapsules can potentially alleviate this problem. Here
      we demonstrate a frequency-domain temperature-modulated fluorescence tomography
      system that could acquire images at high intensity-focused ultrasound resolution
      with use of these nanocapsules. The system is experimentally verified with a
      phantom study, where a 3-mm fluorescence object embedded 2 cm deep in a turbid
      medium is successfully recovered based on both intensity and lifetime contrast.

PMID- 22612131
TI  - Spatial frequency domain tomography of protoporphyrin IX fluorescence in
      preclinical glioma models.
AB  - Multifrequency (0 to 0.3  mm(-1)), multiwavelength (633, 680, 720, 800, and 820
      nm) spatial frequency domain imaging (SFDI) of 5-aminolevulinic acid-induced
      protoporphyrin IX (PpIX) was used to recover absorption, scattering, and
      fluorescence properties of glioblastoma multiforme spheroids in tissue-simulating
      phantoms and in vivo in a mouse model. Three-dimensional tomographic
      reconstructions of the frequency-dependent remitted light localized the depths of
      the spheroids within 500 MUm, and the total amount of PpIX in the reconstructed
      images was constant to within 30% when spheroid depth was varied. In vivo tumor
      to-normal contrast was greater than ~1.5 in reduced scattering coefficient for
      all wavelengths and was ~1.3 for the tissue concentration of deoxyhemoglobin
      (ctHb). The study demonstrates the feasibility of SFDI for providing enhanced
      image guidance during surgical resection of brain tumors.

PMID- 22612132
TI  - Toward real-time virtual biopsy of oral lesions using confocal laser
      endomicroscopy interfaced with embedded computing.
AB  - Oral lesions are conventionally diagnosed using white light endoscopy and
      histopathology. This can pose a challenge because the lesions may be difficult to
      visualise under white light illumination. Confocal laser endomicroscopy can be
      used for confocal fluorescence imaging of surface and subsurface cellular and
      tissue structures. To move toward real-time "virtual" biopsy of oral lesions, we
      interfaced an embedded computing system to a confocal laser endomicroscope to
      achieve a prototype three-dimensional (3-D) fluorescence imaging system. A field
      programmable gated array computing platform was programmed to enable
      synchronization of cross-sectional image grabbing and Z-depth scanning, automate
      the acquisition of confocal image stacks and perform volume rendering.
      Fluorescence imaging of the human and murine oral cavities was carried out using
      the fluorescent dyes fluorescein sodium and hypericin. Volume rendering of
      cellular and tissue structures from the oral cavity demonstrate the potential of
      the system for 3-D fluorescence visualization of the oral cavity in real-time. We
      aim toward achieving a real-time virtual biopsy technique that can complement
      current diagnostic techniques and aid in targeted biopsy for better clinical
      outcomes.

PMID- 22612133
TI  - Performance characterization of an integrated ultrasound, photoacoustic, and
      thermoacoustic imaging system.
AB  - We developed a novel trimodality system for human breast imaging by integrating
      photoacoustic (PA) and thermoacoustic (TA) imaging techniques into a modified
      commercial ultrasound scanner. Because light was delivered with an optical
      assembly placed within the microwave antenna, no mechanical switching between the
      microwave and laser sources was needed. Laser and microwave excitation pulses
      were interleaved to enable PA and TA data acquisition in parallel at a rate of 10
      frames per second. A tube (7 mm inner diameter) filled with oxygenated bovine
      blood or 30 mM methylene blue dye was successfully detected in PA images in
      chicken breast tissue at depths of 6.6 and 8.4 cm, respectively, for the first
      time. The SNRs at these depths reached ~24 and ~15 dB, respectively, by averaging
      200 signal acquisitions. Similarly, a tube (13 mm inner diameter) filled with
      saline solution (0.9%) at a depth of 4.4 cm in porcine fat tissue was
      successfully detected in TA images. The PA axial, lateral, and elevational
      resolutions were 640 MUm, 720 MUm, and 3.5 mm, respectively, suitable for breast
      cancer imaging. A PA noise-equivalent sensitivity to methylene blue solution of
      260 nM was achieved in chicken tissue at a depth of 3.4 cm.

PMID- 22612134
TI  - Discrimination of motile bacteria from filamentous fungi using dynamic speckle.
AB  - We present a dynamic laser speckle method to easily discriminate filamentous
      fungi from motile bacteria in soft surfaces, such as agar plate. The method
      allows the detection and discrimination between fungi and bacteria faster than
      with conventional techniques. The new procedure could be straightforwardly
      extended to different micro-organisms, as well as applied to biological and
      biomedical research, infected tissues analysis, and hospital water and
      wastewaters studies.

PMID- 22612135
TI  - Extracting structural features of rat sciatic nerve using polarization-sensitive
      spectral domain optical coherence tomography.
AB  - We present spectral domain polarization-sensitive optical coherence tomography
      (SD PS-OCT) imaging of peripheral nerves. Structural and polarization-sensitive
      OCT imaging of uninjured rat sciatic nerves was evaluated both qualitatively and
      quantitatively. OCT and its functional extension, PS-OCT, were used to image
      sciatic nerve structure with clear delineation of the nerve boundaries to muscle
      and adipose tissues. A long-known optical effect, bands of Fontana, was also
      observed. Postprocessing analysis of these images provided significant
      quantitative information, such as epineurium thickness, estimates of extinction
      coefficient and birefringence of nerve and muscle tissue, frequency of bands of
      Fontana at different stretch levels of nerve, and change in average birefringence
      of nerve under stretched condition. We demonstrate that PS-OCT combined with
      regular-intensity OCT (compared with OCT alone) allows for a clearer
      determination of the inner and outer boundaries of the epineurium and distinction
      of nerve and muscle based on their birefringence pattern. PS-OCT measurements on
      normal nerves show that the technique is promising for studies on peripheral
      nerve injury.

PMID- 22612136
TI  - Digital simulation of staining in histopathology multispectral images:
      enhancement and linear transformation of spectral transmittance.
AB  - Hematoxylin and eosin (H&E) stain is currently the most popular for routine
      histopathology staining. Special and/or immuno-histochemical (IHC) staining is
      often requested to further corroborate the initial diagnosis on H&E stained
      tissue sections. Digital simulation of staining (or digital staining) can be a
      very valuable tool to produce the desired stained images from the H&E stained
      tissue sections instantaneously. We present an approach to digital staining of
      histopathology multispectral images by combining the effects of spectral
      enhancement and spectral transformation. Spectral enhancement is accomplished by
      shifting the N-band original spectrum of the multispectral pixel with the
      weighted difference between the pixel's original and estimated spectrum; the
      spectrum is estimated using M < N principal component (PC) vectors. The pixel's
      enhanced spectrum is transformed to the spectral configuration associated to its
      reaction to a specific stain by utilizing an N * N transformation matrix, which
      is derived through application of least mean squares method to the enhanced and
      target spectral transmittance samples of the different tissue components found in
      the image. Results of our experiments on the digital conversion of an H&E stained
      multispectral image to its Masson's trichrome stained equivalent show the
      viability of the method.

PMID- 22612137
TI  - Fourier transform infrared spectroscopic imaging of cardiac tissue to detect
      collagen deposition after myocardial infarction.
AB  - Myocardial infarction often leads to an increase in deposition of fibrillar
      collagen. Detection and characterization of this cardiac fibrosis is of great
      interest to investigators and clinicians. Motivated by the significant
      limitations of conventional staining techniques to visualize collagen deposition
      in cardiac tissue sections, we have developed a Fourier transform infrared
      imaging spectroscopy (FT-IRIS) methodology for collagen assessment. The infrared
      absorbance band centered at 1338  cm(-1), which arises from collagen amino acid
      side chain vibrations, was used to map collagen deposition across heart tissue
      sections of a rat model of myocardial infarction, and was compared to
      conventional staining techniques. Comparison of the size of the collagen scar in
      heart tissue sections as measured with this methodology and that of trichrome
      staining showed a strong correlation (R=0.93). A Pearson correlation model
      between local intensity values in FT-IRIS and immuno-histochemical staining of
      collagen type I also showed a strong correlation (R=0.86). We demonstrate that FT
      IRIS methodology can be utilized to visualize cardiac collagen deposition. In
      addition, given that vibrational spectroscopic data on proteins reflect molecular
      features, it also has the potential to provide additional information about the
      molecular structure of cardiac extracellular matrix proteins and their
      alterations.

PMID- 22612138
TI  - Automatic recognition of surface landmarks of anatomical structures of back and
      posture.
AB  - Faulty postures, scoliosis and sagittal plane deformities should be detected as
      early as possible to apply preventive and treatment measures against major
      clinical consequences. To support documentation of the severity of deformity and
      diminish x-ray exposures, several solutions utilizing analysis of back surface
      topography data were introduced. A novel approach to automatic recognition and
      localization of anatomical landmarks of the human back is presented that may
      provide more repeatable results and speed up the whole procedure. The algorithm
      was designed as a two-step process involving a statistical model built upon
      expert knowledge and analysis of three-dimensional back surface shape data.
      Voronoi diagram is used to connect mean geometric relations, which provide a
      first approximation of the positions, with surface curvature distribution, which
      further guides the recognition process and gives final locations of landmarks.
      Positions obtained using the developed algorithms are validated with respect to
      accuracy of manual landmark indication by experts. Preliminary validation proved
      that the landmarks were localized correctly, with accuracy depending mostly on
      the characteristics of a given structure. It was concluded that recognition
      should mainly take into account the shape of the back surface, putting as little
      emphasis on the statistical approximation as possible.

PMID- 22612139
TI  - In vivo preclinical photoacoustic imaging of tumor vasculature development and
      therapy.
AB  - The use of a novel all-optical photoacoustic scanner for imaging the development
      of tumor vasculature and its response to a therapeutic vascular disrupting agent
      is described. The scanner employs a Fabry-Perot polymer film ultrasound sensor
      for mapping the photoacoustic waves and an image reconstruction algorithm based
      upon attenuation-compensated acoustic time reversal. The system was used to
      noninvasively image human colorectal tumor xenografts implanted subcutaneously in
      mice. Label-free three-dimensional in vivo images of whole tumors to depths of
      almost 10 mm with sub-100-micron spatial resolution were acquired in a
      longitudinal manner. This enabled the development of tumor-related vascular
      features, such as vessel tortuosity, feeding vessel recruitment, and necrosis to
      be visualized over time. The system was also used to study the temporal evolution
      of the response of the tumor vasculature following the administration of a
      therapeutic vascular disrupting agent (OXi4503). This revealed the well-known
      destruction and recovery phases associated with this agent. These studies
      illustrate the broader potential of this technology as an imaging tool for the
      preclinical and clinical study of tumors and other pathologies characterized by
      changes in the vasculature.

PMID- 22612140
TI  - Performance of a lookup table-based approach for measuring tissue optical
      properties with diffuse optical spectroscopy.
AB  - Diffuse optical spectroscopy (DOS) provides a powerful tool for fast and
      noninvasive disease diagnosis. The ability to leverage DOS to accurately quantify
      tissue optical parameters hinges on the model used to estimate light-tissue
      interaction. We describe the accuracy of a lookup table (LUT)-based inverse model
      for measuring optical properties under different conditions relevant to
      biological tissue. The LUT is a matrix of reflectance values acquired
      experimentally from calibration standards of varying scattering and absorption
      properties. Because it is based on experimental values, the LUT inherently
      accounts for system response and probe geometry. We tested our approach in tissue
      phantoms containing multiple absorbers, different sizes of scatterers, and
      varying oxygen saturation of hemoglobin. The LUT-based model was able to extract
      scattering and absorption properties under most conditions with errors of less
      than 5 percent. We demonstrate the validity of the lookup table over a range of
      source-detector separations from 0.25 to 1.48 mm. Finally, we describe the rapid
      fabrication of a lookup table using only six calibration standards. This
      optimized LUT was able to extract scattering and absorption properties with
      average RMS errors of 2.5 and 4 percent, respectively.

PMID- 22612141
TI  - Evaluating elastic properties of heterogeneous soft tissue by surface acoustic
      waves detected by phase-sensitive optical coherence tomography.
AB  - The combined use of surface acoustic wave (SAW) and phase-sensitive optical
      coherence tomography (PhS-OCT) is useful to evaluate the elasticity of layered
      biological tissues, such as normal skin. However, the pathological tissue is
      often originated locally, leading to the alternation of mechanical properties
      along both axial and lateral directions. We present a feasibility study on
      whether the SAW technique is sensitive to detect the alternation of mechanical
      property along the lateral direction within tissue, which is important for
      clinical utility of this technique to localize diseased tissue. Experiments are
      carried out on purposely designed tissue phantoms and ex vivo chicken breast
      samples, simulating the localized change of elasticity. A PhS-OCT system is
      employed not only to provide the ultra-high sensitive measurement of the
      generated surface waves on the tissue surface, but also to provide the real time
      imaging of the tissue to assist the elasticity evaluation of the heterogeneous
      tissue. The experimental results demonstrate that with PhS-OCT used as a pressure
      sensor, the SAW is highly sensitive to the elasticity change of the specimen in
      both vertical and lateral directions with a sensing depth of ~5 mm with our
      current system setup, thus promising its useful clinical applications where the
      quantitative elasticity of localized skin diseases is needed to aid in diagnosis
      and treatment.

PMID- 22612142
TI  - Separation of indocyanine green boluses in the human brain and scalp based on
      time-resolved in-vivo fluorescence measurements.
AB  - Non-invasive detection of fluorescence from the optical tracer indocyanine green
      is feasible in the adult human brain when employing a time-domain technique with
      picosecond resolution. A fluorescence-based assessment may offer higher signal-to
      noise ratio when compared to bolus tracking relying on changes in time-resolved
      diffuse reflectance. The essential challenge is to discriminate the fluorescence
      originating from the brain from contamination by extracerebral fluorescence and
      hence to reconstruct the bolus kinetics; however, a method to reliably perform
      the necessary separation is missing. We present a novel approach for the
      decomposition of the fluorescence contributions from the two tissue compartments.
      The corresponding sensitivity functions pertaining to the brain and to the
      extracerebral compartment are directly derived from the in-vivo measurement. This
      is achieved by assuming that during the initial and the late phase of bolus
      transit the fluorescence signal originates largely from one of the compartments.
      Solving the system of linear equations allows one to approximate time courses of
      a bolus for each compartment. We applied this method to repetitive measurements
      on two healthy subjects with an overall 34 boluses. A reconstruction of the bolus
      kinetics was possible in 62% of all cases.

PMID- 22612143
TI  - Lifetime-based photoacoustic oxygen sensing in vivo.
AB  - The determination of oxygen levels in blood and other tissues in vivo is critical
      for ensuring proper body functioning, for monitoring the status of many diseases,
      such as cancer, and for predicting the efficacy of therapy. Here we demonstrate,
      for the first time, a lifetime-based photoacoustic technique for the measurement
      of oxygen in vivo, using an oxygen sensitive dye, enabling real time
      quantification of blood oxygenation. The results from the main artery in the rat
      tail indicated that the lifetime of the dye, quantified by the photoacoustic
      technique, showed a linear relationship with the blood oxygenation levels in the
      targeted artery.

PMID- 22612144
TI  - Determination of absorption changes from moments of distributions of times of
      flight of photons: optimization of measurement conditions for a two-layered
      tissue model.
AB  - Time-resolved near-infrared spectroscopy allows for depth-selective determination
      of absorption changes in the adult human head that facilitates separation between
      cerebral and extra-cerebral responses to brain activation. The aim of the present
      work is to analyze which combinations of moments of measured distributions of
      times of flight (DTOF) of photons and source-detector separations are optimal for
      the reconstruction of absorption changes in a two-layered tissue model
      corresponding to extra- and intra-cerebral compartments. To this end we
      calculated the standard deviations of the derived absorption changes in both
      layers by considering photon noise and a linear relation between the absorption
      changes and the DTOF moments. The results show that the standard deviation of the
      absorption change in the deeper (superficial) layer increases (decreases) with
      the thickness of the superficial layer. It is confirmed that for the deeper layer
      the use of higher moments, in particular the variance of the DTOF, leads to an
      improvement. For example, when measurements at four different source-detector
      separations between 8 and 35 mm are available and a realistic thickness of the
      upper layer of 12 mm is assumed, the inclusion of the change in mean time of
      flight, in addition to the change in attenuation, leads to a reduction of the
      standard deviation of the absorption change in the deeper tissue layer by a
      factor of 2.5. A reduction by another 4% can be achieved by additionally
      including the change in variance.

PMID- 22612145
TI  - Light-scattering flow cytometry for identification and characterization of blood
      microparticles.
AB  - We describe a novel approach to study blood microparticles using the scanning
      flow cytometer, which measures light scattering patterns (LSPs) of individual
      particles. Starting from platelet-rich plasma, we separated spherical
      microparticles from non-spherical plasma constituents, such as platelets and cell
      debris, based on similarity of their LSP to that of sphere. This provides a label
      free method for identification (detection) of microparticles, including those
      larger than 1 MUm. Next, we rigorously characterized each measured particle,
      determining its size and refractive index including errors of these estimates.
      Finally, we employed a deconvolution algorithm to determine size and refractive
      index distributions of the whole population of microparticles, accounting for
      largely different reliability of individual measurements. Developed methods were
      tested on a blood sample of a healthy donor, resulting in good agreement with
      literature data. The only limitation of this approach is size detection limit,
      which is currently about 0.5 MUm due to used laser wavelength of 0.66 MUm.

PMID- 22612146
TI  - Quantitative analysis of optical properties of flowing blood using a photon-cell
      interactive Monte Carlo code: effects of red blood cells' orientation on light
      scattering.
AB  - Optical properties of flowing blood were analyzed using a photon-cell interactive
      Monte Carlo (pciMC) model with the physical properties of the flowing red blood
      cells (RBCs) such as cell size, shape, refractive index, distribution, and
      orientation as the parameters. The scattering of light by flowing blood at the He
      Ne laser wavelength of 632.8 nm was significantly affected by the shear rate. The
      light was scattered more in the direction of flow as the flow rate increased.
      Therefore, the light intensity transmitted forward in the direction perpendicular
      to flow axis decreased. The pciMC model can duplicate the changes in the photon
      propagation due to moving RBCs with various orientations. The resulting RBC's
      orientation that best simulated the experimental results was with their long axis
      perpendicular to the direction of blood flow. Moreover, the scattering
      probability was dependent on the orientation of the RBCs. Finally, the pciMC code
      was used to predict the hematocrit of flowing blood with accuracy of
      approximately 1.0 HCT%. The photon-cell interactive Monte Carlo (pciMC) model can
      provide optical properties of flowing blood and will facilitate the development
      of the non-invasive monitoring of blood in extra corporeal circulatory systems.

PMID- 22612147
TI  - Noninvasive in vivo optical assessment of blood brain barrier permeability and
      brain tissue drug deposition in rabbits.
AB  - Osmotic disruption of the blood brain barrier (BBB) by intraarterial mannitol
      injection is sometimes the key step for the delivery of chemotherapeutic drugs to
      brain tissue. BBB disruption (BBBD) with mannitol, however, can be highly
      variable and could impact local drug deposition. We use optical pharmacokinetics,
      which is based on diffuse reflectance spectroscopy, to track in vivo brain tissue
      concentrations of indocyanine green (ICG), an optical reporter used to monitor
      BBBD, and mitoxantrone (MTX), a chemotherapy agent that does not deposit in brain
      tissue without BBBD, in anesthetized New Zealand white rabbits. Results show a
      significant increase in the tissue ICG concentrations with BBBD, and our method
      is able to track the animal-to-animal variation in tissue ICG and MTX
      concentrations after BBBD. The tissue concentrations of MTX increase with barrier
      disruption and are found to be correlated to the degree of disruption, as
      assessed by the ICG prior to the injection of the drug. These findings should
      encourage the development of tracers and optical methods capable of quantifying
      the degree of BBBD, with the goal of improving drug delivery.

PMID- 22612148
TI  - Photochemical internalization of bleomycin for glioma treatment.
AB  - We study the use of photochemical internalization (PCI) for enhancing
      chemotherapeutic response to malignant glioma cells in vitro. Two models are
      studied: monolayers consisting of F98 rat glioma cells and human glioma spheroids
      established from biopsy-derived glioma cells. In both cases, the cytotoxicity of
      aluminum phthalocyanine disulfonate (AlPcS2a)-based PCI of bleomycin was compared
      to AlPcS(2a)-photodynamic therapy (PDT) and chemotherapy alone. Monolayers and
      spheroids were incubated with AlPcS(2a) (PDT effect), bleomycin (chemotherapy
      effect), or AlPcS(2a)+bleomycin (PCI effect) and were illuminated (670 nm).
      Toxicity was evaluated using colony formation assays or spheroid growth kinetics.
      F98 cells in monolayer/spheroids were not particularly sensitive to the effects
      of low radiant exposure (1.5  J/cm(2) @ 5 mW/cm(2)) AlPcS(2a)-PDT. Bleomycin was
      moderately toxic to F98 cells in monolayer at relatively low concentrations
      incubation of F98 cells in 0.1 MUg/ml for 4 h resulted in 80% survival, but less
      toxic in human glioma spheroids respectively. In both in vitro systems
      investigated, a significant PCI effect is seen. PCI using 1.5 J/cm(2) together
      with 0.25 MUg/ml bleomycin resulted in approximately 20% and 18% survival of F98
      rat glioma cells and human glioma spheroids, respectively. These results show
      that AlPcS(2a)-mediated PCI can be used to enhance the efficacy of
      chemotherapeutic agents such as bleomycin in malignant gliomas.

PMID- 22612149
TI  - Fat tissue histological study at indocyanine green-mediated
      photothermal/photodynamic treatment of the skin in vivo.
AB  - Histological slices of skin samples with the subcutaneous adipose tissue after
      photothermal/photodynamic treatment are analyzed. In the case of subcutaneous
      indocyanine green injection and 808-nm diode laser exposure of the rat skin site
      in vivo, the greatest changes in tissue condition were observed. Processes were
      characterized by dystrophy, necrosis, and desquamation of the epithelial cells,
      swelling and necrosis of the connective tissue, and widespread necrosis of the
      subcutaneous adipose tissue. The obtained data are useful for safe layer-by-layer
      dosimetry of laser illumination of ICG-stained adipose tissue for treatment of
      obesity and cellulite.

PMID- 22612150
TI  - Bleaching of plasmon-resonance absorption of gold nanorods decreases efficiency
      of cell destruction.
AB  - When irradiated with nanosecond laser pulses, gold nanoparticles allow for
      manipulation or destruction of cells and proteins with high spatial and temporal
      precision. Gold nanorods are especially attractive, because they have an up-to-20
      fold stronger absorption than a sphere of equal volume, which is shifted to the
      optical window of tissue. Thus, an increased efficiency of cell killing is
      expected with laser pulses tuned to the near infrared absorption peak of the
      nanorods. In contrast to the higher-absorption, experiments showed a reduced
      efficacy of cell killing. In order to explain this discrepancy, transient
      absorption of irradiated nanorods was measured and the observed change of
      particle absorption was theoretically analyzed. During pulsed irradiation a
      strong transient and permanent bleaching of the near-infrared absorption band
      occurred. Both effects limit the ability of nanorods to destroy cells by
      nanocavitation. The existence of nanocavitation and transient bleaching was
      corroborated by optoacoustic measurements.

PMID- 22612154
TI  - Dorsal metacarpal artery flaps with extensor indices tendons for reconstruction
      of digital defects.
AB  - INTRODUCTION: Distally based dorsal metacarpal artery (DMCA) flaps are an
      established technique for the reconstruction of extensive finger defects. In many
      cases, such defects also include an injury of the extension tendon over the
      proximal and distal finger joint, which can lead to a reduced range of motion or
      finger deformation such as boutonniere deformity. To prevent this, operative
      techniques are necessary that allow complete defect coverage while simultaneously
      stabilizing the extension apparatus. METHODS: In two cases, DMCA flaps were
      combined with vascularized extensor indices tendons for the reconstruction of
      extensive dorsal finger skin and soft tissue defects, particularly when tendon
      and bone are exposed. RESULTS: After three weeks of postoperative immobilization,
      physiotherapy could be intensified. In a six months' follow-up, the results
      obtained from the standpoint of both function and appearance were excellent, the
      flaps remained viable at all times and full-finger length and sensory function
      were maintained. Regarding operation time, pain and finger appearance, both
      patients stated satisfaction. CONCLUSION: The vascularized tendon incorporated in
      DMCA flaps provides a sufficient method to restore a satisfactory finger function
      and prevent finger deformity, arthrodesis, or amputation, especially in cases
      with severe injuries of the extension apparatus.

PMID- 22612155
TI  - Evaluation of a 13-hexyl-berberine hydrochloride topical gel formulation.
AB  - 13-hexyl-berberine hydrochloride (HB-13) is a derivative from berberine which
      finds widespread applications in the treatment of infectious pathogens including
      fungi, bacteria, parasites and viruses. As our continuing efforts for treatment
      of herpes simplex virus (HSV), we studied the topical delivery and safety of HB
      13 in a gel formulation (0.5%) in a pig model. Our studies demonstrated the
      maximal HB-13 concentration was 2.51 ug/mL, which was more than the half maximal
      inhibitory concentration (IC50) as we previously reported. In addition, there was
      no sign of irritation or histological aberrance for stripped skin continuously
      applied with 0.5% HB-13 gel for 21 days. In conclusion, 0.5% HB-13 gel can
      achieve effective anti-HSV concentration in the dermis and it is safe to use.

PMID- 22612156
TI  - MRS in early and presymptomatic carriers of a novel octapeptide repeat insertion
      in the prion protein gene.
AB  - To evaluate the proton magnetic resonance (MR) spectroscopy ((1) H MRS) changes
      in carriers of a novel octapeptide repeat insertion in the prion protein gene
      (PRNP) and family history of frontotemporal dementia with ataxia. Four at-risk
      mutation carriers and 13 controls were compared using single voxel, short TE, (1)
      H MRS from the posterior cingulate gyrus. The mutation carriers had an increased
      choline/creatine, P = .003 and increased myoinositol/creatine ratio, P = .003.
      (1) H MRS identified differences in markers of glial activity and choline
      metabolism in pre- and early-symptomatic carriers of a novel PRNP gene
      octapeptide insertion. These findings expand the possible diagnostic utility of
      (1) H MRS in familial prion disorders.

PMID- 22612157
TI  - Buckwheat trypsin inhibitor with helical hairpin structure belongs to a new
      family of plant defence peptides.
AB  - A new peptide trypsin inhibitor named BWI-2c was obtained from buckwheat
      (Fagopyrum esculentum) seeds by sequential affinity, ion exchange and reversed
      phase chromatography. The peptide was sequenced and found to contain 41 amino
      acid residues, with four cysteine residues involved in two intramolecular
      disulfide bonds. Recombinant BWI-2c identical to the natural peptide was produced
      in Escherichia coli in a form of a cleavable fusion with thioredoxin. The 3D
      (three-dimensional) structure of the peptide in solution was determined by NMR
      spectroscopy, revealing two antiparallel alpha-helices stapled by disulfide
      bonds. Together with VhTI, a trypsin inhibitor from veronica (Veronica
      hederifolia), BWI-2c represents a new family of protease inhibitors with an
      unusual alpha-helical hairpin fold. The linker sequence between the helices
      represents the so-called trypsin inhibitory loop responsible for direct binding
      to the active site of the enzyme that cleaves BWI-2c at the functionally
      important residue Arg(19). The inhibition constant was determined for BWI-2c
      against trypsin (1.7*10(-1)0 M), and the peptide was tested on other enzymes,
      including those from various insect digestive systems, revealing high selectivity
      to trypsin-like proteases. Structural similarity shared by BWI-2c, VhTI and
      several other plant defence peptides leads to the acknowledgement of a new
      widespread family of plant peptides termed alpha-hairpinins.

PMID- 22612158
TI  - Myxoid variant of anaplastic large cell lymphoma involving the skin: a case
      report.
AB  - We report the case of a 62-year-old white male who presented with a 2.6-cm
      ulcerating mass on the skin of the left buttock and ipsilateral inguinal
      lymphadenopathy. Microscopic sections of the skin lesion showed a nodular and
      plaque-like growth pattern of a mixed cellular infiltrate throughout the dermis
      and subcutaneous tissue with prominent myxoid change. There was a dominant
      population of medium-sized mitotically active atypical cells that expressed CD30,
      CD4 and EMA. These atypical cells were mixed with eosinophils, neutrophils,
      mature lymphocytes and histiocytes. Tissue from the inguinal lymphadenopathy
      showed similar pathologic features, although no residual lymph node tissue was
      present. A diagnosis of secondary anaplastic large cell lymphoma, myxoid variant,
      with skin and lymph node/perinodal soft tissue involvement was rendered at the
      time of complete excision of the buttock mass. The patient received five cycles
      of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy
      with complete resolution of lymphadenopathy and no residual cutaneous disease. He
      was disease-free by PET/CT scan and physical examination at 16 months after
      chemotherapy. We present this case to highlight the histopathologic and
      immunophenotypic features of this entity with a discussion of the differential
      diagnosis and a review of the literature.

PMID- 22612160
TI  - Excessive response-repetition costs under task switching: how response inhibition
      amplifies response conflict.
AB  - The size of response-repetition (RR) costs, which are usually observed on task
      switch trials, strongly varies between conditions with univalent and bivalent
      stimuli. To test whether top-down or bottom-up processes can account for this
      effect, we assessed in Experiment 1 baselines for univalent and bivalent stimulus
      conditions (i.e., for stimuli that are associated with either 1 or 2 tasks).
      Experiment 2 examined whether the proportion of these stimulus types affects RR
      costs. As the size of RR costs was independent of proportion, a top-down
      explanation could be excluded. However, there was an increase in RR costs if the
      current stimulus induced a response conflict. To account for this effect, we
      proposed an amplification of response conflict account. It assumes that the basic
      mechanism that leads to RR costs amplifies response conflict, which, in turn,
      increases RR costs. Experiment 3 confirmed this bottom-up explanation by showing
      that the increase in RR costs varies with previous-trial congruency, which is
      known to affect RR costs. Experiment 4 showed that the increase can also be found
      with univalent stimuli that induce response conflict. Altogether, the results are
      in line with a response inhibition account of RR costs. Implications for
      alternative accounts are also discussed. (PsycINFO Database Record (c) 2013 APA,
      all rights reserved).

PMID- 22612159
TI  - A one dose experimental cholera vaccine.
AB  - The number of cholera vaccine doses required for immunity is a constraint during
      epidemic cholera. Protective immunity following one dose of multiple Vibrio
      cholerae (Vc) colonization factors (Inaba LPS El Tor, TcpA, TcpF, and CBP-A) has
      not been directly tested even though individual Vc colonization factors are the
      protective antigens. Inaba LPS consistently induced vibriocidal and protective
      antibodies at low doses. A LPS booster, regardless of dose, induced highly
      protective secondary sera. Vc protein immunogens emulsified in adjuvant were
      variably immunogenic. CBP-A was proficient at inducing high IgG serum titers
      compared with TcpA or TcpF. After one immunization, TcpA or TcpF antisera
      protected only when the toxin co-regulated pilus operon of the challenge Vc was
      induced by AKI culture conditions. CBP-A was not consistently able to induce
      protection independent of the challenge Vc culture conditions. These results
      reveal the need to understand how best to leverage the 'right' Vc immunogens to
      obtain durable immunity after one dose of a cholera subunit vaccine. The
      dominance of the protective anti-LPS antibody response over other Vc antigen
      antibody response needs to be controlled to find other protective antigens that
      can add to anti-LPS antibody-based immunity.

PMID- 22612161
TI  - Habituation of the irrelevant sound effect: evidence for an attentional theory of
      short-term memory disruption.
AB  - Immediate serial recall is seriously disrupted by to-be-ignored sound. According
      to the embedded-processes model, auditory distractors elicit attentional
      orienting that draws processing resources away from the recall task. The model
      predicts that interference should be attenuated after repeated exposure to the
      auditory distractors. Previous failures to observe evidence for habituation can
      be explained by assuming that habituation to complex distractor features depends
      on the availability of working memory resources. Here we demonstrate that the
      irrelevant sound effect is attenuated after passive listening to the auditory
      distractors during a preexposure phase prior to the serial recall task.
      Experiment 1 shows that the irrelevant sound effect is abolished after 20 min of
      passive listening to the distractor speech. Experiments 2-4 show that irrelevant
      sound interference is significantly reduced after listening to distractors for 45
      s. As predicted by the habituation hypothesis, an attenuation of interference
      occurs only when the distractor material matches the material played in the
      preexposure phase (Experiment 5). The results support an attentional
      conceptualization of the irrelevant sound effect.

PMID- 22612162
TI  - The effects of prior knowledge on incidental category learning.
AB  - This article describes 5 experiments investigating the role of prior knowledge in
      incidental category learning. Experiments 1 to 3 showed that prior knowledge
      improved learning only if the categories in a given set were related to
      contrasting themes; there was no consistent knowledge effect if the categories
      were related to the same theme. Experiments 4 and 5 showed that diagnostic verbal
      labels facilitated the learning of non-thematic categories but provided no
      additional benefit when the categories were already related to contrasting
      themes. In terms of the category invention framework proposed by Clapper (2007),
      these results imply that prior knowledge provides an effective cue for
      discovering separate categories, as well as helping people segregate the features
      of those different categories in memory and so improving their recall. The
      relevance of these results to other types of category learning tasks is
      discussed.

PMID- 22612163
TI  - Parallel object activation and attentional gating of information: evidence from
      eye movements in the multiple object naming paradigm.
AB  - Do we access information from any object we can see, or do we access information
      only from objects that we intend to name? In 3 experiments using a modified
      multiple object naming paradigm, subjects were required to name several objects
      in succession when previews appeared briefly and simultaneously in the same
      location as the target as well as at another location. In Experiment 1, preview
      benefit-faster processing of the target when the preview was related (a mirror
      image of the target) compared to unrelated (semantically and phonologically)-was
      found for the preview in the target location but not a location that was never to
      be named. In Experiment 2, preview benefit was found if a related preview
      appeared in either the target location or the third-to-be-named location.
      Experiment 3 showed the difference between results from the first 2 experiments
      was not due to the number of objects on the screen. These data suggest that
      attention serves to gate visual input about objects based on the intention to
      name them and that information from one intended-to-be-named object can
      facilitate processing of an object in another location.

PMID- 22612164
TI  - On the specificity of sequential congruency effects in implicit learning of motor
      and perceptual sequences.
AB  - Individuals experience less interference from conflicting information following
      events that contain conflicting information. Recently, Jimenez, Lupianez, and
      Vaquero (2009) demonstrated that such adaptations to conflict occur even when the
      source of conflict arises from implicit knowledge of sequences. There is
      accumulating evidence that momentary changes in adaptations made in response to
      conflicting information are conflict-type specific (e.g., Funes, Lupianez, &
      Humphreys, 2010a), suggesting that there are multiple modes of control. The
      current study examined whether conflict-specific sequential congruency effects
      occur when the 2 sources of conflict are implicitly learned. Participants
      implicitly learned a motor sequence while simultaneously learning a perceptual
      sequence. In a first experiment, after learning the 2 orthogonal sequences,
      participants expressed knowledge of the 2 sequences independently of each other
      in a transfer phase. In Experiments 2 and 3, within each sequence, the presence
      of a single control trial disrupted the expression of this specific type of
      learning on the following trial. There was no evidence of cross-conflict
      modulations in the expression of sequence learning. The results suggest that the
      mechanisms involved in transient shifts in conflict-specific control, as
      reflected in sequential congruency effects, are also engaged when the source of
      conflict is implicit.

PMID- 22612165
TI  - Interference within the focus of attention: working memory tasks reflect more
      than temporary maintenance.
AB  - One approach to understanding working memory (WM) holds that individual
      differences in WM capacity arise from the amount of information a person can
      store in WM over short periods of time. This view is especially prevalent in WM
      research conducted with the visual arrays task. Within this tradition, many
      researchers have concluded that the average person can maintain approximately 4
      items in WM. The present study challenges this interpretation by demonstrating
      that performance on the visual arrays task is subject to time-related factors
      that are associated with retrieval from long-term memory. Experiment 1
      demonstrates that memory for an array does not decay as a product of absolute
      time, which is consistent with both maintenance- and retrieval-based explanations
      of visual arrays performance. Experiment 2 introduced a manipulation of temporal
      discriminability by varying the relative spacing of trials in time. We found that
      memory for a target array was significantly influenced by its temporal
      compression with, or isolation from, a preceding trial. Subsequent experiments
      extend these effects to sub-capacity set sizes and demonstrate that changes in
      the size of k are meaningful to prediction of performance on other measures of WM
      capacity as well as general fluid intelligence. We conclude that performance on
      the visual arrays task does not reflect a multi-item storage system but instead
      measures a person's ability to accurately retrieve information in the face of
      proactive interference.

PMID- 22612167
TI  - Stress assignment in reading Italian polysyllabic pseudowords.
AB  - In 4 naming experiments we investigated how Italian readers assign stress to
      pseudowords. We assessed whether participants assign stress following
      distributional information such as stress neighborhood (the proportion and number
      of existent words sharing orthographic ending and stress pattern) and whether
      such distributional information affects naming speed. Experiments 1 and 2 tested
      how readers assign stress to pseudowords. The results showed that participants
      assign stress on the basis of the pseudowords' stress neighborhood, but only when
      this orthographic/phonological information is widely represented in the lexicon.
      Experiments 3 and 4 tested the naming speed of pseudowords with different stress
      patterns. Participants were faster in reading pseudowords with antepenultimate
      than with penultimate stress. The effect was not driven by distributional
      information, but it was related to the stage of articulation planning. Overall,
      the experiments showed that, under certain conditions, readers assign stress
      using orthographic/phonological distributional information. However, the
      distributional information does not speed up pseudoword naming, which is affected
      by stress computation at the level of the articulation planning of the stimulus.
      It is claimed that models of reading aloud and speech production should be merged
      at the level of phonological encoding, when segmental and metrical information
      are assembled and articulation is planned.

PMID- 22612166
TI  - Effects of emotional valence and arousal on recollective and nonrecollective
      recall.
AB  - The authors investigated the effects of valence and arousal on memory using a
      dual-process model that quantifies recollective and nonrecollective components of
      recall without relying on metacognitive judgments to separate them. The results
      showed that valenced words increased reconstruction (a component of
      nonrecollective retrieval) relative to neutral words. In addition, the authors
      found that positive valence increased recollective retrieval in comparison to
      negative valence, whereas negative valence increased nonrecollective retrieval
      relative to positive valence. The latter effect, however, depended on arousal: It
      was reliable only when arousal was high. The present findings supported the
      notion that emotional valence is a conceptual gist because it affected
      nonrecollective retrieval and because subjects' recall protocols were clustered
      by valence. The results challenge the hypothesis that valence affects only
      recollection, and they clarify previous inconsistent findings about the effects
      of emotion on memory accuracy and brain activity.

PMID- 22612168
TI  - Evidence for a limited-cascading account of written word naming.
AB  - We address the issue of how information flows within the written word production
      system by examining written object-naming latencies. We report 4 experiments in
      which we manipulate variables assumed to have their primary impact at the level
      of object recognition (e.g., quality of visual presentation of pictured objects),
      at the level of semantic processing (contextual constraint), and at the level of
      the lexical retrieval of orthographic word forms (e.g., word frequency). In
      Experiment 1, pictures were presented either in color or in black and white and
      had names with either high-to-low or low-to-high frequency trajectories. Both
      factors had reliable but entirely additive effects on written naming times. In
      Experiment 2, pictures were presented clearly, in visual noise or blurred, and
      had names of either high or low word frequency. Again, both factors had reliable
      but additive effects on written naming latencies. In Experiments 3 and 4,
      pictures were preceded by a sentence that provided either strong or weak
      contextual constraint and had names of either high or low word frequency. These 2
      variables interacted: The advantage for high-frequency words was observed only
      with low contextual constraint. We argue that, in combination, these findings
      support a limited-cascading account of written word production.

PMID- 22612169
TI  - Additive and interactive effects in semantic priming: Isolating lexical and
      decision processes in the lexical decision task.
AB  - The present study sheds light on the interplay between lexical and decision
      processes in the lexical decision task by exploring the effects of lexical
      decision difficulty on semantic priming effects. In 2 experiments, we increased
      lexical decision difficulty by either using transposed letter wordlike nonword
      distracters (e.g., JUGDE; Experiment 1) or by visually degrading targets
      (Experiment 2). Although target latencies were considerably slowed by both
      difficulty manipulations, stimulus quality-but not nonword type-moderated priming
      effects, consistent with recent work by Lupker and Pexman (2010). To characterize
      these results in a more fine-grained manner, data were also analyzed at the level
      of response time (RT) distributions, using a combination of ex-Gaussian,
      quantile, and diffusion model analyses. The results indicate that for clear
      targets, priming was reflected by distributional shifting of comparable magnitude
      across different nonword types. In contrast, priming of degraded targets was
      reflected by shifting and an increase in the tail of the distribution. We discuss
      how these findings, along with others, can be accommodated by an embellished
      multistage activation model that incorporates retrospective prime retrieval and
      decision-based mechanisms.

PMID- 22612170
TI  - The contribution of working memory to fluid reasoning: capacity, control, or
      both?
AB  - Fluid reasoning shares a large part of its variance with working memory capacity
      (WMC). The literature on working memory (WM) suggests that the capacity of the
      focus of attention responsible for simultaneous maintenance and integration of
      information within WM, as well as the effectiveness of executive control exerted
      over WM, determines individual variation in both WMC and reasoning. In 6
      experiments, we used a modified n-back task to test the amount of variance in
      reasoning that is accounted for by each of these 2 theoretical constructs. The
      capacity of the focus accounted for up to 62% of variance in fluid reasoning,
      while the recognition of stimuli encoded outside of the focus was not related to
      reasoning ability. Executive control, measured as the ability to reject
      distractors identical to targets but presented in improper contexts, accounted
      for up to 13% of reasoning variance. Multiple analyses indicated that capacity
      and control predicted non-overlapping amounts of variance in reasoning.

PMID- 22612171
TI  - No role for motor affordances in visual working memory.
AB  - Motor affordances have been shown to play a role in visual object identification
      and categorization. The present study explored whether working memory is likewise
      supported by motor affordances. Use of motor affordances should be disrupted by
      motor interference, and this effect should be larger for objects that have motor
      affordances than for objects that do not. In 5 experiments participants performed
      a working memory task on photographs of manipulable and nonmanipulable objects.
      Concurrent motor, verbal, or visual tasks interfered with memory performance in
      general but did not interact with object manipulability. Thus, there was no
      evidence that motor affordances support visual working memory.

PMID- 22612172
TI  - Auditory memory distortion for spoken prose.
AB  - Observers often remember a scene as containing information that was not presented
      but that would have likely been located just beyond the observed boundaries of
      the scene. This effect is called boundary extension (BE; e.g., Intraub &
      Richardson, 1989). Previous studies have observed BE in memory for visual and
      haptic stimuli, and the present experiments examined whether BE occurred in
      memory for auditory stimuli (prose, music). Experiments 1 and 2 varied the amount
      of auditory content to be remembered. BE was not observed, but when auditory
      targets contained more content, boundary restriction (BR) occurred. Experiment 3
      presented auditory stimuli with less content and BR also occurred. In Experiment
      4, white noise was added to stimuli with less content to equalize the durations
      of auditory stimuli, and BR still occurred. Experiments 5 and 6 presented trained
      stories and popular music, and BR still occurred. This latter finding ruled out
      the hypothesis that the lack of BE in Experiments 1-4 reflected a lack of
      familiarity with the stimuli. Overall, memory for auditory content exhibited BR
      rather than BE, and this pattern was stronger if auditory stimuli contained more
      content. Implications for the understanding of general perceptual processing and
      directions for future research are discussed.

PMID- 22612173
TI  - Plausibility effects when reading one- and two-character words in Chinese:
      evidence from eye movements.
AB  - Eye movements of Chinese readers were monitored as they read sentences containing
      a critical character that was either a 1-character word or the initial character
      of a 2-character word. Due to manipulation of the verb prior to the target word,
      the 1-character target word (or the first character of the 2-character target
      word) was either plausible or implausible, as an independent word, at the point
      at which it appeared, whereas the 2-character word was always plausible. The eye
      movement data showed that the plausibility manipulation did not exert an
      influence on the reading of the 2-character word or its component characters.
      However, plausibility significantly influenced reading of the 1-character target
      word. These results suggest that processes of semantic integration in reading
      Chinese are performed at a word level, instead of a character level, and that
      word segmentation must take place very early in the course of processing.

PMID- 22612174
TI  - The dynamics of access to groups in working memory.
AB  - The finding that participants leave a pause between groups when attempting serial
      recall of temporally grouped lists has been taken to indicate access to a
      hierarchical representation of the list in working memory. An alternative
      explanation is that the dynamics of serial recall solely reflect output (rather
      than memorial) processes, with the temporal pattern at input merely suggesting a
      basis for the pattern of output buffering. Three experiments are presented here
      that disentangle input structure from output buffering in serial recall. In
      Experiment 1, participants were asked to recall a subset of visually presented
      digits from a temporally grouped list in their original order, where either
      within-group position or group position was kept constant. In Experiment 2,
      participants performed more standard serial recall of spoken digits, and input
      and output position were dissociated by asking participants to initiate recall
      from a post-cued position in the list. In Experiment 3, participants were asked
      to serially recall temporally grouped lists of visually presented digits where
      the grouping structure was unpredictable, under either articulatory suppression
      or silent conditions. The 3 experiments point to a tight linkage between implied
      memorial structures (i.e., the pattern of grouping at encoding) and the output
      structure implied by retrieval times and call into question a purely motoric
      account of the dynamics of recall.

PMID- 22612175
TI  - Clarification regarding epidemiologic concepts.

PMID- 22612177
TI  - Synthetic cannabinoids and "bath salts"  should be considered drugs of abuse.

PMID- 22612179
TI  - New feature to help physicians implement AHRQ effective health care reviews.

PMID- 22612180
TI  - Mind over body: hypnosis during childbirth.

PMID- 22612181
TI  - Self-monitoring of blood glucose in patients with type 2 diabetics not using
      insulin.

PMID- 22612182
TI  - Therapies for children with autism spectrum disorders.

PMID- 22612183
TI  - Diabetic nephropathy--the family physician's role.
AB  - Nearly one-half of persons with chronic kidney disease have diabetes mellitus.
      Diabetes accounted for 44 percent of new cases of kidney failure in 2008.
      Diabetic nephropathy, also called diabetic kidney disease, is associated with
      significant macrovascular risk, and is the leading cause of kidney failure in the
      United States. Diabetic nephropathy usually manifests after 10 years' duration of
      type 1 diabetes, but may be present at diagnosis of type 2 diabetes. Screening
      for microalbuminuria should be initiated five years after diagnosis of type 1
      diabetes and at diagnosis of type 2 diabetes. Screening for microalbuminuria with
      a spot urine albumin/creatinine ratio identifies the early stages of nephropathy.
      Positive results on two of three tests (30 to 300 mg of albumin per g of
      creatinine) in a six-month period meet the diagnostic criteria for diabetic
      nephropathy. Because diabetic nephropathy may also manifest as a decreased
      glomerular filtration rate or an increased serum creatinine level, these tests
      should be included in annual monitoring. Preventive measures include using an
      angiotensin- converting enzyme inhibitor or angiotensin II receptor blocker in
      normotensive persons. Optimizing glycemic control and using an angiotensin
      converting enzyme inhibitor or angiotensin II receptor blocker to control blood
      pressure slow the progression of diabetic nephropathy, but implementing intensive
      glycemic and blood pressure control is associated with more adverse outcomes. Low
      protein diets may also decrease adverse renal outcomes and mortality in persons
      with diabetic nephropathy.

PMID- 22612184
TI  - Diagnosis and management of adult attention-deficit/hyperactivity disorder.
AB  - Attention-deficit/hyperactivity disorder in childhood can persist into adulthood
      in at least 30 percent of patients, with 3 to 4 percent of adults meeting the
      Diagnostic and Statistical Manual of Mental Disorders, 4th ed., diagnostic
      criteria. A number of conditions, such as thyroid disease, mood disorders, and
      substance use disorders, have symptoms similar to those of attention
      deficit/hyperactivity disorder and should be considered in the differential
      diagnosis. Steroids, antihistamines, anticonvulsants, caffeine, and nicotine also
      can have adverse effects that mimic attention-deficit/hyperactivity disorder
      symptoms. Proper diagnosis and treatment can improve daily functioning. Diagnosis
      relies on a thorough clinical history, supported by a number of rating scales
      that take five to 20 minutes to complete, depending on the scale. Clinical
      guidelines recommend stimulants and the nonstimulant atomoxetine as first-line
      treatments, followed by antidepressants. Cognitive behavior therapy has also been
      shown to be helpful as adjunctive treatment with medication. For adults with
      coexisting depression, the combination of an antidepressant and stimulants has
      been shown to be safe and effective. To monitor for misuse or diversion of
      stimulants, family physicians should consider using a controlled substances
      agreement and random urine drug screening in addition to regular follow-up
      visits.

PMID- 22612185
TI  - Managing adverse birth outcomes: helping parents and families cope.
AB  - Unexpected adverse fetal and neonatal outcomes (e.g., stillbirth, birth trauma,
      congenital anomalies) present a crisis for the family and the medical care team.
      In cases of stillbirth, the family physician should be flexible in supporting the
      parents' choices, validate the loss, and work as a team with the nursing staff.
      Psychosocial support includes offering counseling services, assessing women for
      postpartum depression and anxiety, and considering the effect of the loss on the
      entire family. Although infants with birth asphyxia or major anomalies may
      require transfer to facilities with a neonatal intensive care unit, the physician
      will usually provide ongoing care for the mother in the postpartum period. A
      comprehensive assessment can determine the etiology of fetal demise in most
      cases, which may guide future preconception and maternity care. Women with a
      previous adverse pregnancy outcome may have increased psychological stress in a
      subsequent pregnancy. Knowledge of community resources will facilitate care for
      the mother and her partner or family. Physicians may need to seek peer support to
      cope with their own feelings of loss.

PMID- 22612186
TI  - Information from your doctor. pregnancy loss.

PMID- 22612187
TI  - Reddish-violet, reticular discoloration on the legs.

PMID- 22612188
TI  - Tapentadol (nucynta) for treatment of pain.

PMID- 22612190
TI  - Responses to article regarding a diagnostic approach to pruritus.

PMID- 22612191
TI  - Responses to article regarding a diagnostic approach to pruritus.

PMID- 22612192
TI  - The ethical aspects of medical research.

PMID- 22612193
TI  - Reaching target hemoglobin level and having a functioning arteriovenous fistula
      significantly improve one year survival in twice weekly hemodialysis.
AB  - INTRODUCTION: This is a prospective study of a cohort of 1011 patients maintained
      on regular hemodialysis (HD) in Khartoum, Sudan, studied in the year 2009 and
      reevaluated one year later. Their survival rates in November 2010 were related to
      their baseline characteristics. METHODS: Demographic and clinical data of studied
      patients was collected by direct patient interviews and dialysis records
      revision. Survival rates were calculated using the Kaplan Meier method. RESULTS:
      Patients had a median age of 45 years and a median duration on dialysis of 25
      months. Two thirds of patients were males and 4.2% were children. Studied
      patients had a one-year survival rate of 86%. Most patients (74.8%) received
      twice weekly HD, and their survival rate was lower than patients receiving thrice
      weekly HD (85% versus 89%, P = 0.06). The strongest independent predictors of
      mortality were lack of a documented measure of dialysis adequacy (HR = 2.7, P =
      0.00), poor functional capacity (HR = 2.4, P = 0.00), lack of a functioning AV
      fistula (HR = 2.0, P = 0.00), age >= 65 years (HR = 1.6, P = 0.02) and
      cardiovascular disease (HR = 1.5, P = 0.04). Patients with hemoglobin level < 10
      g/dl had significantly lower survival rates (81% versus 92%, P = 0.00) compared
      to other patients. HD patients' perception of their own general health was also
      significantly correlated to their survival rates (P = 0.00). CONCLUSION: Patients
      on thrice weekly HD did marginally better than those on twice weekly HD. In the
      latter group, however, having an AV fistula and a hemoglobin level of > 10 g/dl
      appeared to have a positive effect on their survival. Twice weekly HD could be
      acceptable for many patients provided other aspects of renal care are cared for
      adequately.

PMID- 22612194
TI  - Clinical course of acute pancreatitis in chronic kidney disease patients in a
      single kidney center (PGTi) in Karachi.
AB  - INTRODUCTION: The aim of this study was to assess the clinical course, etiology
      and complications of acute pancreatitis among chronic kidney disease (CKD)
      patients in a tertiary care renal center in Karachi. METHODS: We retrospectively
      evaluated the clinical course of CKD patients who presented to our emergency room
      with signs and symptoms of acute pancreatitis over a period of two years.
      RESULTS: During the study period, 247 CKD patients presented to our emergency
      room with symptoms suggestive of acute pancreatitis. Only 43 patients (17.4%) had
      more than a threefold increase in serum amylase and/or lipase levels fulfilling
      the diagnostic criteria of acute pancreatitis. They included 25 pre-dialysis CKD
      patients (58.13%) and 18 end stage renal failure patients (41.86%) on regular
      hemodialysis (HD). Among the 25 pre-dialysis CKD patients, 17 patients developed
      acute kidney injury (AKI), ten of whom required temporary HD. Twelve of those
      patients (70%) returned back to their baseline renal functions after 3-4 weeks.
      Gallstones were the cause of pancreatitis in seven patients (16.3%) while no
      cause was identified in 29 patients (67.4%). Nine patients (20.9%) developed
      multi-organ failure and 12 patients (27.9%) required admission to the intensive
      care unit (ICU). All patients survived except for one patient (2.3%) who died in
      the ICU. patients with less than threefold increase in serum amylase and lipase
      levels responded well to conservative management and had a favorable clinical
      course. CONCLUSION: In severe acute pancreatitis the mortality rate can be as
      high as 40-58% especially in association with comorbid conditions. In this series
      of CKD patients however, the overall mortality rate was 2.3%, probably due to the
      predominance of milder forms of pancreatitis.

PMID- 22612195
TI  - The pattern of histologically-proven acute post-infectious glomerulonephritis in
      Tunisian adults seen in 1976-2004.
AB  - INTRODUCTION: Acute post-infectious glomerulonephritis (APIGN) is uncommon in
      adults. It is widely recognized that the prognosis of APIGN is good in children.
      There is however little information about its long-term prognosis in adults.
      METHODS: Between December 1976 and October 2004, 148 adult cases of APIGN were
      managed in our center. We retrospectively reviewed these patients' records and
      evaluated their clinical course and outcome. RESULTS: The mean age of studied
      patients was 36 +/- 15 years, and the male to female ratio was 2.3. The most
      common site of preceding infection was the respiratory tract (68.8%). At
      presentation, 89.2% had nephritic syndrome and 9.4% had rapidly progressive
      glomerulonephritis. Proteinuria was observed in 99.3%, hematuria in 95.3%,
      peripheral edema in 89.2% and hypertension in 81.8%. Most patients (60.7%) had
      acute kidney injury and four patients (2.7%) required dialysis. Renal biopsy
      showed diffuse endocapillary proliferative glomerulonephritis in 88.8% of
      patients, associated with extracapillary proliferation in 12%. After a median
      follow-up of 2.5 year, only two patients died and 16.12% of patients had
      persistent clinical and/or biological abnormality. Chronic kidney disease was
      noted in 10 patients (6.75%) including four patients (2.7%) who progressed to end
      stage renal disease. Poor prognostic factors included nephrotic range
      proteinuria, extracapillary proliferation in renal biopsy, acute kidney injury
      and the need for dialysis. CONCLUSION: In this cohort of patients, APIGN
      progressed to chronic kidney disease in less than 10% of patients.

PMID- 22612196
TI  - Informed consent for inclusion into clinical trials: a serious subject to note in
      the developing world.
AB  - INTRODUCTION: Informed consent is a critical issue especially in conducting
      clinical trials that expose human life to medical or surgical interventions. It
      necessitates a long and complex process through which the participant is
      presented with all potential favorable and non-favorable consequences upon
      getting enrolled in the study. REVIEW: The process of taking informed consent is
      well-understood in developed countries, with every effort taken to enhance and
      maintain the autonomy of patients and their right to make an informed choice of
      whether to participate or not. This may not be the case in the developing
      world.The information given to patients before the trial might not be properly
      developed and presented, an issue that can result in serious threat to the
      decision-making process. On the other hand, investigators should remember that
      enrolling people into a trial with no potential benefit for themselves cannot be
      considered ethical. In the current debate, we aim to address the issue of how
      respectfully and ethically clinical research trials can be done on human subjects
      and what we can do to enhance the practice in an ethical context. CONCLUSION:
      Development of a system through which we could warrant all rights of study
      participants in all cases around the world seems far from view. However, if we
      are in doubt about the ethics of a clinical trial, we can ask ourselves: "what
      would we do, if we were in the same position our patients are in now?"

PMID- 22612197
TI  - Thrombotic thrombocytopenic purpura and systemic lupus erythematosus: a rare and
      life-threatening association.
AB  - INTRODUCTION: The association between thrombotic thrombocytopenic purpura (TTP)
      and systemic lupus erythematosus (SLE) is uncommon. Diagnosis is often difficult
      because of their clinical and biological similarities. The presence of TTP in SLE
      worsens the prognosis and causes high mortality in the absence of early
      therapeutic interventions. CASE REPORT: We report the case of a 20 year-old man,
      admitted with nephrotic range proteinuria, hematuria and rapidly progressive
      renal failure. He also had anemia, thrombocytopenia and pericardial effusion. The
      diagnosis of SLE was made based on these clinical findings along with positive
      antinuclear and anti dsDNA antibodies. Renal biopsy revealed class IV/ V lupus
      nephritis (LN) with active lesions of thrombotic microangiopathy. The evolution
      of neurological deficit, persistent thrombocytopenia and active microangiopathic
      changes suggested the diagnosis of associated TTP. The patient was treated
      initially with corticosteroids and cyclophosphamide. Plasmapheresis could only be
      started 16 days later. Mycophenolate mofetil and rituximab were successively
      tried in the absence of improvement in renal function and persistent
      thrombocytopenia. The patient's neurological condition deteriorated necessitating
      transfer to the intensive care unit and mechanical ventilation. There he
      developed pneumonia and died of septic shock two months after presentation.
      CONCLUSION: The coexistence of TTP and SLE needs to be considered early in SLE
      patients with complicated course. It may not respond to the conventional
      immunosuppressive treatment of SLE.

PMID- 22612198
TI  - Crossed renal ectopia coexisting with nephrolithiasis in a young Nigerian man.
AB  - INTRODUCTION: Renal ectopia or ectopic kidney is a congenital anomaly in which
      one or both kidneys are located in an unusual position. It results from the
      kidney failing to ascend properly from its origin in the true pelvis. In some
      cases, one kidney may cross over (crossed renal ectopia) so that both kidneys are
      on the same side of the body. When a crossover occurs, the two kidneys may grow
      together and become fused (crossed fused renal ectopia). Renal ectopia is
      generally uncommon; its coexistence with nephrolithiasis is even rarer. Due to
      its variable presentations, it is usually discovered incidentally, especially
      when investigating patients for abdominal pain. Treatment may be conservative
      when renal function is preserved and no complication is associated. CASE REPORT:
      we highlight the unusual occurrence of renal ectopia with nephrolithiasis in a 34
      year-old Nigerian businessman who presented to the renal clinic of our hospital
      with a three-month history of intermittent dull right flank pain radiating to the
      right groin. Physical examination revealed right lumbar tenderness without
      guarding. The rest of the examination was unremarkable. An abdominal ultrasound
      scan done revealed a linear calculus in the right renal collecting system but the
      left kidney was not visualised. An intravenous urogram (IVU) showed a crossed
      ectopic kidney with nephrolithiasis. The patient was treated conservatively and
      his kidney function has remained stable. CONCLUSION: This case report describes
      the relatively uncommon finding of crossed renal ectopia associated with
      nephrolithiasis.

PMID- 22612199
TI  - Attentional biases for threat in at-risk daughters and mothers with lifetime
      panic disorder.
AB  - Children of parents with panic disorder (PD) have high risk for developing
      anxiety disorders. However, the mechanisms involved in transmission of risk are
      uncertain. Cognitive models of anxiety propose that information-processing biases
      underlie anxiety vulnerability; in particular, attentional biases for threat.
      Consequently, this study examined attentional biases in mothers with lifetime PD
      and their daughters (aged 9-14 years). Sixty mother-daughter dyads (n = 120) were
      recruited to the study; half the mothers had lifetime PD (i.e., either a current
      or past history of PD), and half had no psychiatric history. Attentional biases
      were assessed using a visual-probe task with pictorial and word stimuli related
      to physical-health threat. Stimulus duration was varied to examine the time
      course of attentional biases (initial orienting and maintained attention).
      Results showed an attentional bias for threat in daughters of mothers with
      lifetime PD, compared with daughters of mothers with no PD history. Specifically,
      at-risk daughters had an attentional bias for physical-health threat cues (words
      and pictures) at the longer stimulus duration of 1250 ms (but not at 500 ms). In
      addition, attentional bias for threat in girls was associated with increased
      physical-health threat worries. Mothers with lifetime PD did not significantly
      differ from mothers with no PD history on the indices of attentional bias. The
      findings are discussed in terms of an attentional threat-monitoring strategy in
      at-risk girls and argue against the view that there is simple transmission of an
      anxiety-related attentional processing style across generations.

PMID- 22612203
TI  - When is a team not a team?

PMID- 22612200
TI  - Validity of DSM-IV attention deficit/hyperactivity disorder symptom dimensions
      and subtypes.
AB  - Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV)
      criteria for attention deficit/hyperactivity disorder (ADHD) specify two
      dimensions of inattention and hyperactivity-impulsivity symptoms that are used to
      define three nominal subtypes: predominantly hyperactive-impulsive type (ADHD-H),
      predominantly inattentive type (ADHD-I), and combined type (ADHD-C). To aid
      decision making for DSM-5 and other future diagnostic systems, a comprehensive
      literature review and meta-analysis of 546 studies was completed to evaluate the
      validity of the DSM-IV model of ADHD. Results indicated that DSM-IV criteria
      identify individuals with significant and persistent impairment in social,
      academic, occupational, and adaptive functioning when intelligence, demographic
      factors, and concurrent psychopathology are controlled. Available data
      overwhelmingly support the concurrent, predictive, and discriminant validity of
      the distinction between inattention and hyperactivity-impulsivity symptoms, and
      indicate that nearly all differences among the nominal subtypes are consistent
      with the relative levels of inattention and hyperactivity-impulsivity symptoms
      that define the subtypes. In contrast, the DSM-IV subtype model is compromised by
      weak evidence for the validity of ADHD-H after first grade, minimal support for
      the distinction between ADHD-I and ADHD-C in studies of etiological influences,
      academic and cognitive functioning, and treatment response, and the marked
      longitudinal instability of all three subtypes. Overall, we conclude that the DSM
      IV ADHD subtypes provide a convenient clinical shorthand to describe the
      functional and behavioral correlates of current levels of inattention and
      hyperactivity-impulsivity symptoms, but do not identify discrete subgroups with
      sufficient long-term stability to justify the classification of distinct forms of
      the disorder. Empirical support is stronger for an alternative model that would
      replace the subtypes with dimensional modifiers that reflect the number of
      inattention and hyperactivity-impulsivity symptoms at the time of assessment.
      (PsycINFO Database Record (c) 2012 APA, all rights reserved).

PMID- 22612204
TI  - Back to the future: the way forward in health care reform.

PMID- 22612205
TI  - The state of family medicine.

PMID- 22612206
TI  - Family physicians need to think outside the box.

PMID- 22612207
TI  - Private practice is at a crossroads.

PMID- 22612208
TI  - Annual wellness visits don't provide added value.

PMID- 22612210
TI  - Medical apps: making your mobile device a medical device.

PMID- 22612211
TI  - Preparing for and recovering from a natural disaster.

PMID- 22612213
TI  - Nine practice sale pitfalls to avoid.

PMID- 22612214
TI  - Six characteristics of effective practice teams.

PMID- 22612222
TI  - The problem with multitasking.

PMID- 22612224
TI  - Drug tolerability in assisted reproduction techniques: a longitudinal study.
AB  - A longitudinal, observational prospective panel cohort study of 61 patients
      lasting one year was undertaken. Explanatory variables included sociodemographic
      factors along with factors related to the underlying pathology as well as the
      protocol used and the type of treatment received. These variables were analyzed
      both individually and in combination to account for confounding effects and model
      interactions. A generalized estimating equation (GEE) model was constructed for
      each adverse effect. Associations were calculated as odds ratios (OR).
      Confounding variables related to drug tolerability were identified. Follitropin
      alpha and cetrorelix exhibited the poorest safety profile. With respect to local
      adverse drug reactions (ADEs), the results obtained in our study point to
      statistically significant tolerability improvements for menotropin when
      administered in insemination. For gastrointestinal ADEs, ganirelix was the drug
      that showed the highest tolerability in in vitro treatments whereas follitropin
      alpha showed the lowest tolerability in insemination treatments. Diverse factors
      related to assisted reproduction techniques (ART) influence the incidence of
      adverse effects. Each drug has a different safety profile with possible
      interactions depending on the type of assisted reproduction therapy used.

PMID- 22612223
TI  - The G2385R variant of leucine-rich repeat kinase 2 associated with Parkinson's
      disease is a partial loss-of-function mutation.
AB  - Autosomal-dominant missense mutations in LRRK2 (leucine-rich repeat kinase 2) are
      a common genetic cause of PD (Parkinson's disease). LRRK2 is a multidomain
      protein with kinase and GTPase activities. Dominant mutations are found in the
      domains that have these two enzyme activities, including the common G2019S
      mutation that increases kinase activity 2-3-fold. However, there is also a
      genetic variant in some populations, G2385R, that lies in a C-terminal WD40
      domain of LRRK2 and acts as a risk factor for PD. In the present study we show
      that the G2385R mutation causes a partial loss of the kinase function of LRRK2
      and deletion of the C-terminus completely abolishes kinase activity. This effect
      is strong enough to overcome the kinase-activating effects of the G2019S mutation
      in the kinase domain. Hsp90 (heat-shock protein of 90 kDa) has an increased
      affinity for the G2385R variant compared with WT (wild-type) LRRK2, and
      inhibition of the chaperone binding combined with proteasome inhibition leads to
      association of mutant LRRK2 with high molecular mass native fractions that
      probably represent proteasome degradation pathways. The loss-of-function of
      G2385R correlates with several cellular phenotypes that have been proposed to be
      kinase-dependent. These results suggest that the C-terminus of LRRK2 plays an
      important role in maintaining enzymatic function of the protein and that G2385R
      may be associated with PD in a way that is different from kinase-activating
      mutations. These results may be important in understanding the differing
      mechanism(s) by which mutations in LRRK2 act and may also have implications for
      therapeutic strategies for PD.

PMID- 22612225
TI  - Nitric oxide-dependent CYP2B degradation is potentiated by a cytokine-regulated
      pathway and utilizes the immunoproteasome subunit LMP2.
AB  - CYP2B proteins in rat hepatocytes undergo NO-dependent proteolytic degradation,
      but the mechanisms and the reasons for the specificity towards only certain P450
      (cytochrome P450) enzymes are yet unknown. In the present study we found that
      down-regulation of CYP2B proteins by the NO donor NOC-18 is accelerated by
      pretreatment of the hepatocytes with IL-1 (interleukin-1beta) in the presence of
      an NO synthase inhibitor, suggesting that an NO-independent action of IL-1
      contributes to the lability of CYP2B proteins. The immunoproteasome subunit LMP2
      (large multifunctional peptidase 2) was significantly expressed in hepatocytes
      under basal conditions, and IL-1 induced LMP2 within 6-12 h of treatment. CYP2B
      protein degradation in response to IL-1 was attenuated by the selective LMP2
      inhibitor UK-101, but not by the LMP7 inhibitor IPSI. The results show that LMP2
      contributes to the NO-dependent degradation of CYP2B proteins, and suggest that
      induction of LMP2 may be involved in the potentiation of this degradation by IL
      1.

PMID- 22612226
TI  - Inhibition of mammalian target of rapamycin reduces epileptogenesis and blood
      brain barrier leakage but not microglia activation.
AB  - PURPOSE: Previous studies have shown that inhibition of the mammalian target of
      rapamycin (mTOR) pathway with rapamycin prevents epileptogenesis after
      pharmacologically induced status epilepticus (SE) in rat models of temporal lobe
      epilepsy. Because rapamycin is also known for its immunosuppressant properties we
      hypothesized that one of the mechanisms by which it exerts this effect could be
      via suppression of brain inflammation, a process that has been suggested to play
      a major role in the development and progression of epilepsy. METHODS: Rats were
      treated with rapamycin or vehicle once daily for 7 days (6 mg/kg/day, i.p.)
      starting 4 h after the induction of SE, which was evoked by electrical
      stimulation of the angular bundle. Hereafter rapamycin was administered every
      other day until rats were sacrificed, 6 weeks after SE. Video
      electroencephalography was used to monitor the occurrence of seizures. Neuronal
      death, synaptic reorganization, and microglia and astrocyte activation were
      assessed by immunohistologic staining. Fluorescein was administered to quantify
      blood-brain barrier leakage. KEY FINDINGS: Rapamycin treatment did not alter SE
      severity and duration compared to vehicle treatment rats. Rapamycin-treated rats
      developed hardly (n = 9) or no (n = 3) seizures during the 6-week treatment,
      whereas vehicle-treated rats showed a progressive increase of seizures starting 1
      week after SE (mean 8 +/- 2 seizures per day during the sixth week). Cell loss
      and sprouting that normally occur after SE were prominent but on average
      significantly less in rapamycin-treated rats versus vehicle-treated rats.
      Nevertheless, various inflammation markers (CD11b/c and CD68) were dramatically
      upregulated and not significantly different between post-SE groups. Of interest,
      blood-brain barrier leakage was barely detected in the rapamycin-treated group,
      whereas it was prominent in the vehicle-treated group. SIGNIFICANCE: mTOR
      inhibition led to strong reduction of seizure development despite the presence of
      microglia activation, suggesting that effects of rapamycin on seizure development
      are not due to a control of inflammation. Whether the effects on blood-brain
      barrier leakage in rapamycin-treated rats are a consequence of seizure
      suppressing properties of the drug, or contribute to a real antiepileptogenic
      effect still needs to be determined.

PMID- 22612227
TI  - Probing the interactions of macrolide antibiotics with membrane-mimetics by NMR
      spectroscopy.
AB  - Interactions of macrolide antibiotics with biological membranes contribute to
      their bioavailability but are also involved in the formation of phospholipidosis,
      which is caused by the inhibition of phospholipase A(1) activity. We determined
      the interaction strength and localization of macrolide antibiotics with membrane
      mimetics. Macrolides bind to membrane-mimetics with the positively charged amino
      groups being close to the micelle surface and thereby protect the lipids from
      being degraded by phospholipase A(1) rather than inhibiting the enzyme.

PMID- 22612228
TI  - Confusion over antibiotic resistance: ecological correlation is not evidence of
      causation.

PMID- 22612229
TI  - Listeria monocytogenes growth dynamics on produce: a review of the available data
      for predictive modeling.
AB  - Several listeriosis outbreaks have been linked to the consumption of fresh or
      processed produce in recent years. One major determinant of the listeriosis risk
      is the ability of a food to support growth of Listeria monocytogenes during
      storage. However, data regarding the ability to support growth of L.
      monocytogenes are scarce or nonexisting for many produce commodities. Here we
      synthesize the available data regarding growth behavior of L. monocytogenes on
      produce, compare the growth data with listeriosis outbreak data, and evaluate the
      adequacy of the data for predictive modeling. Growth rates and maximum L.
      monocytogenes population densities differed markedly among produce commodities,
      and post-harvest processing had a considerable effect on growth dynamics for
      certain commodities such as tomatoes. However, data scarcity prevented reliable
      estimation of growth rates for many commodities. Produce outbreaks seemed
      frequently associated with processed produce and often involved storage under
      suboptimal conditions (e.g., at room temperature for several hours or for several
      months in the refrigerator) or environmental cross-contamination after
      processing. However, no clear associations between high growth rates of L.
      monocytogenes on fresh produce and outbreaks were detected. In conclusion,
      produce commodities differ in the supported growth rate of L. monocytogenes, the
      maximum attainable L. monocytogenes population density, and possibly in the
      impact of post-harvest processing, but data are currently insufficient to predict
      growth behavior, and the listeriosis risk appears to be also governed by
      additional factors.

PMID- 22612230
TI  - Distal extremity necrosis as a manifestation of cutaneous polyarteritis nodosa:
      case report and review of the acute management of a pediatric patient.
AB  - We present the case of an 8-year-old girl who presented with distal extremity
      necrosis of the hands, feet, nose, and ears as an acute manifestation of
      cutaneous polyarteritis nodosa (CPAN). She was emergently managed with
      intravenous steroids, nifedipine, sildenafil, pentoxifylline, nitroglycerin
      paste, aspirin, low-molecular-weight heparin, and intravenous gamma globulin. The
      necrosis was controlled, and reperfusion was attained to salvage the extremities.
      It is important for clinicians to be aware that acute distal extremity necrosis
      can be a manifestation of CPAN in children. Etiology is often not clear on
      presentation, but once infection is excluded, acute management with systemic
      steroids and systemic vasodilators is indicated regardless of the cause. Iloprost
      and bosentan may represent options for adjunctive vasodilators. More studies are
      needed to create guidelines for the acute and long-term management of these
      children. Close follow-up of children with CPAN, especially with a history of
      vaso-occlusive symptoms, is important to allow prompt intervention in the event
      of distal extremity infarction.

PMID- 22612231
TI  - Discovery and biochemical characterization of Plasmodium thioredoxin reductase
      inhibitors from an antimalarial set.
AB  - Plasmodium falciparum is the most prevalent and deadly species of the human
      malaria parasites, and thioredoxin reductase (TrxR) is an enzyme involved in the
      redox response to oxidative stress. Essential for P. falciparum survival, the
      enzyme has been highlighted as a promising target for novel antimalarial drugs.
      Here we report the discovery and characterization of seven molecules from an
      antimalarial set of 13533 compounds through single-target TrxR biochemical
      screens. We have produced high-purity, full-length, recombinant native enzyme
      from four Plasmodium species, and thioredoxin substrates from P. falciparum and
      Rattus norvegicus. The enzymes were screened using a unique, high-throughput, in
      vitro native substrate assay, and we have observed selectivity between the
      Plasmodium species and the mammalian form of the enzyme. This has indicated
      differences in their biomolecular profiles and has provided valuable insights
      into the biochemical mechanisms of action of compounds with proven antimalarial
      activity.

PMID- 22612232
TI  - A novel nanovesicular carrier system to deliver drug topically.
AB  - CONTEXT: Ketoconazole, a lipophilic drug with a large molecular weight of 531.44
      Da and a limiting aqueous solubility of 0.04 mg/ml is expected to show a poor
      transport across the skin. OBJECTIVE: The work describes usefulness of a novel,
      surfactant based elastic vesicular drug carrier system (SEVs), for enhanced
      dermal delivery. MATERIALS AND METHODS: The system constitutes Span 60 and an
      edge activator (Tween 80) and was characterized and monitored for safety and
      potential to target deeper mice skin layers. RESULTS: Nanosized (126 nm), elastic
      vesicles showed significantly high skin penetration and retention as compared to
      free drug suspension. Incorporation into different bases especially a hydrogel
      showed a significant retention which was even more than the market formulation
      (Nizral((r))). Safety was confirmed as cytotoxicity and acute dermal
      irritation/corrosion. Topically applied fluorescent vesicles labeled with 6
      carboxyfluorescein, on mice skin, were observed intact in dermal layer 6 h post
      application. CONCLUSION: The results of the present study indicate that SEVs can
      be used to enhance skin delivery of the model high molecular weight and poorly
      water-soluble drug ketoconazole. The developed nanorange system is an effective
      system for targeting deeper mice skin layers which may be translated to human
      skin with suitable modifications, if required.

PMID- 22612233
TI  - Infrared-optical double resonance spectroscopic investigation of
      trifluoromethylphenols and their water complexes.
AB  - The hydrogen bonding behavior of trifluoromethylphenols and their water complexes
      were investigated using IR-UV double resonance spectroscopy. Both ortho- and meta
      trifluoromethylphenols exist in the syn conformer, which is the global minimum in
      both the cases. The IR spectrum in the O-H stretching region reveals the absence
      of an intramolecular O-H...F hydrogen bond in the syn-o-trifluoromethylphenol,
      which is in contrast to the results reported in the literature. The water
      complexes of both o-trifluoromethylphenol and m-trifluoromethylphenol are
      characterized by formation of O-H...O hydrogen bonds between the donor phenolic
      OH group and the acceptor water molecule. In addition, the o
      trifluoromethylphenol-(water)(2) complex was also observed.

PMID- 22612234
TI  - Multimetallic alloy nanotubes with nanoporous framework.
AB  - One-dimensional nanotubes (NTs) that consist of multiple metallic components are
      promising platforms for potential applications, whereas only a few synthetic
      methods of multimetallic NTs have been reported to date. In the present work, we
      developed a general synthesis route for the production of uniform multicomponent
      one-dimensional tubular nanostructures with various combinations of Pt, Pd, and
      Ag by using ZnO nanowires (NWs) as sacrificial templates. The ZnO NWs serve not
      only as physical templates but also as nucleation sites for the reduction of
      metal precursors, and thereby several metal precursors could be reduced
      simultaneously to produce multimetallic NTs. By using this approach, Pt-Pd, Pt
      Ag, and Pd-Ag binary alloy NTs, and even Pt-Pd-Ag ternary alloy NTs could be
      successfully prepared. The prepared Pt-Pd binary alloy NTs exhibited improved
      electrocatalytic activity and stability toward ethanol oxidation due to their
      characteristic tubular morphology with well-interconnected nanoporous framework
      and synergism between two constituent metals. Furthermore, our approach can
      facilitate the fabrication of patterned multimetallic NT arrays on solid and
      flexible substrates with strong mechanical robustness. The present templating
      method does not require any extra steps to remove templates or additional
      surfactants which are often required to control the shape of nanostructures. This
      strategy offers a convenient, versatile, low-cost, and highly valuable approach
      to the fabrication of multimetallic nanostructures with various components and
      compositions.

PMID- 22612235
TI  - Molecular-scale structure of uranium(VI) immobilized with goethite and phosphate.
AB  - The molecular-scale immobilization mechanisms of uranium uptake in the presence
      of phosphate and goethite were examined by extended X-ray absorption fine
      structure (EXAFS) spectroscopy. Wet chemistry data from U(VI)-equilibrated
      goethite suspensions at pH 4-7 in the presence of ~100 MUM total phosphate
      indicated changes in U(VI) uptake mechanisms from adsorption to precipitation
      with increasing total uranium concentrations and with increasing pH. EXAFS
      analysis revealed that the precipitated U(VI) had a structure consistent with the
      meta-autunite group of solids. The adsorbed U(VI), in the absence of phosphate at
      pH 4-7, formed bidentate edge-sharing, = Fe(OH)(2)UO(2), and bidentate corner
      sharing, (= FeOH)(2)UO(2), surface complexes with respective U-Fe coordination
      distances of ~3.45 and ~4.3 A. In the presence of phosphate and goethite, the
      relative amounts of precipitated and adsorbed U(VI) were quantified using linear
      combinations of the EXAFS spectra of precipitated U(VI) and phosphate-free
      adsorbed U(VI). A U(VI)-phosphate-Fe(III) oxide ternary surface complex is
      suggested as the dominant species at pH 4 and total U(VI) of 10 MUM or less on
      the basis of the linear combination fitting, a P shell indicated by EXAFS, and
      the simultaneous enhancement of U(VI) and phosphate uptake on goethite. A
      structural model for the ternary surface complex was proposed that included a
      single phosphate shell at ~3.6 A (U-P) and a single iron shell at ~4.3 A (U-Fe).
      While the data can be explained by a U-bridging ternary surface complex, (=
      FeO)(2)UO(2)PO(4), it is not possible to statistically distinguish this scenario
      from one with P-bridging complexes also present.

PMID- 22612236
TI  - Early-mid term follow-up results of percutaneous closure of the interatrial
      septal defects with occlutech figulla devices: a single center experience.
AB  - BACKGROUND: Percutaneous closure of secundum type atrial septal defect (ASD) and
      patent foramen ovale (PFO) has gained widespread use in recent years. Herein, we
      evaluated the safety and efficacy of the Occlutech(r) Figulla devices for PFO and
      ASD closure in a reference tertiary center. METHODS: All 143 patients (46.9%
      male, mean age 39.3 +/- 12.2 years) who underwent transcatheter PFO (n = 85) and
      ASD (n = 58) closure with Occlutech(r) Figulla devices between February 2009 and
      October 2011 were included in this study. An echocardiographic follow-up
      examination was performed at the 1st, 6th, and 12th month visits. RESULTS: The
      devices were successfully implanted in all 143 patients (100%). In-hospital
      periprocedural complications were device embolization (0.7%; 1 ASD patient),
      atrial fibrillation (1.4%; 1 ASD and 1 PFO patients), supraventricular
      tachycardia (0.7%; 1 PFO patient), and vascular access hematoma (0.7%; 1 ASD
      patient). Among ASD patients, 2 patients had trivial (jet width <1 mm in
      diameter) and 1 patient had small (1-2 mm) residual shunts before hospital
      discharge, which disappeared after the 6-month visit. During the mean 15.4 +/-
      9.6 months follow-up, all patients were asymptomatic and no ischemic stroke,
      cardiac perforation, device erosion, embolization, thrombus formation, or
      malposition of the device was observed. CONCLUSIONS: Percutaneous PFO and
      secundum type ASD closure with the novel Occlutech(r) Figulla Occluder devices
      without left atrial central pin and with significantly reduced meshwork was safe,
      feasible, and effective.

PMID- 22612237
TI  - Identification and characterization of the mammalian association and actin
      nucleating domains in the Rickettsia conorii autotransporter protein, Sca2.
AB  - Establishment of infection by spotted fever group rickettsial species is
      dependent on the ability of these bacteria to adhere to and invade the host
      endothelium. Recent studies have attributed these processes to a handful of
      rickettsial surface proteins from the surface cell antigen (sca) family of
      autotransporters. A rickettsial autotransporter from Rickettsia conorii, Sca2,
      has been shown to be sufficient to mediate both adherence and invasion of human
      endothelial cells and to participate in intracellular actin-based motility. Here
      we identify a region of Sca2 capable of interacting with the mammalian cell
      surface and show that this function of Sca2 is independent and separable from its
      actin nucleation activity. Furthermore, pre-incubation of mammalian cells with
      the Sca2 mammalian association region prior to R. conorii infection can
      competitively inhibit rickettsial invasion, suggesting that Sca2 plays an
      important role in the initial interaction with mammalian cells. Together, our
      results demonstrate that the Sca2 autotransporter protein in R. conorii contains
      distinct functional domains that likely are involved in mediating cellular
      interactions at the plasma membrane and the host cytosol.

PMID- 22612238
TI  - Primary human hepatocytes from metabolic-disordered children recreate highly
      differentiated liver-tissue-like spheroids on alginate scaffolds.
AB  - Human hepatocyte transplantation has not been routinely established as an
      alternative to liver transplantation in liver disease due to low cell engraftment
      rates. Preimplantation in vitro engineering of liver tissue using primary human
      hepatocytes on three-dimensional scaffolds could be an alternative model.
      Alginate bioscaffolds were seeded with 1*10(6) hepatocytes freshly isolated from
      the livers of three children suffering from different metabolic disorders. During
      a culture period of 14 days only a marginal loss of hepatocytes was observed via
      measurement of DNA content per scaffold. Formation of hepatocyte spheroids was
      detected from day 3 onward using transmission light microscopy. Biochemical
      assays for albumin, alpha1-antitrypsin, and urea revealed excellent metabolic
      function with its maximum at day 7. Low lactate dehydrogenase enzyme release
      demonstrated minor cellular membrane damage. Hematoxylin and eosin and periodic
      acid Schiff staining displayed high cell viability and well-preserved glycogen
      storage until day 7. Immunofluorescent staining of hepatocyte nuclear factor 4,
      zonula occludens protein 1, and cytokeratin 18 revealed highly differentiated
      hepatocytes in spheroids with a tissue-like structure on scaffolds. Fluorescent
      labeling of cytochrome P450 and bile canaliculi demonstrated detoxification
      ability as well as a well-shaped bile canaliculi network. Almost constant
      expression levels in most target genes were detected by quantitative real-time
      polymerase chain reaction. The results of TUNEL reaction implicated a safe
      scaffold-dissolving procedure. Our results indicate that alginate scaffolds
      provide a favorable microenvironment for liver neo-tissue recreation and
      regeneration. Further, we demonstrate that livers from children with inherited
      metabolic disorders could serve as an alternative cell source for in vitro
      experiments.

PMID- 22612239
TI  - Rituximab before splenectomy in adults with primary idiopathic thrombocytopenic
      purpura: a meta-analysis.
AB  - Primary immune thrombocytopenia (ITP) is an acquired immune-mediated disorder
      with absence of any underlying cause. Corticosteroids are the standard initial
      treatment. Splenectomy is the main second-line treatment. A trend to delay or
      avoid splenectomy has developed thanks to new agents like rituximab. Few studies
      have assessed the response rate to rituximab in chronic ITP. We performed the
      first meta-analysis of randomized clinical trials and observational studies on
      rituximab as an effective splenectomy-avoiding option in adult chronic ITP.
      Overall methods were adapted from published guidelines for meta-analysis (meta
      analysis of observational studies in epidemiology and preferred reporting items
      for systematic reviews and meta-analyses). Two haematologist investigators
      carried out study selection and data extraction independently, recording overall
      response rate (ORR) and complete response (CR) as primary assessment criteria. Of
      364 records were identified through electronic databases. Of 19 retrospective or
      prospective observational studies were retained after removing duplicate studies
      and full-text analyses. The ORR was 57% (95% confidence interval [CI]: 48-65),
      for 368 non-splenectomized patients after rituximab; CR was 41% (95% CI: 0.33
      0.51) for 346 patients. Results were stable for ORR and CR in all sub-analyses.
      In univariate or multivariate mixed-effect meta-regression, age was the most
      relevant effect. According to our results, rituximab should be used in earlier in
      non-splenectomized patients.

PMID- 22612240
TI  - Apocrine adenomyoepithelioma--a rare but distinctive primary sweat gland
      neoplasm.
AB  - Adenomyoepithelioma is a rare, microscopically distinctive tumor of the skin.
      This article explores an example that presented in the inguinal area in a 29-year
      old woman, mimicking adenopathy. Histopathologically, the tumor included two
      different areas: a cystic area consisting of tubules and glands in hyalinized
      stroma and a solid area showing marked myoepithelial proliferation. The diagnosis
      of adenomyoepithelioma was confirmed by the presence of a biphasic immunoprofile,
      with expression of cytokeratins and epithelial membrane antigen in the glandular
      epithelium and with expression of vimentin and smooth muscle actin in the
      myoepithelial cells. An interesting novel finding was the expression of claudin
      10 by myoepithelial cells, which to date has not been reported in the literature.
      The absence of metaplastic changes in the tumor stroma is crucial in the
      differential diagnosis with apocrine mixed tumor. Given that soft tissue
      adenomyoepithelioma is a benign tumor believed to originate from conventional
      sweat glands, its classification as a cutaneous myoepithelial neoplasm seems
      reasonable.

PMID- 22612241
TI  - Margin-free, en bloc resection of a multilevel cervical chordoma with C-2
      involvement: case report with 2-year follow-up and description of operative
      technique.
AB  - The purpose of this technical/case report is to demonstrate that the appropriate
      oncological principle of margin-free, tumour en bloc removal can be successfully
      achieved in a large multilevel chordoma with C-2 involvement, with limited
      morbidity. Although technically challenging, such an approach offers the
      patient's best chance for cure.

PMID- 22612242
TI  - Long-term clinical and angiographic outcomes in patients with spontaneous cervico
      cranial arterial dissections treated with stent placement.
AB  - BACKGROUND: Limited data exist regarding the long-term clinical and angiographic
      outcomes of patients with spontaneous cervico-cranial arterial dissection treated
      with stent placement. OBJECTIVE: To report the immediate and long-term clinical
      and angiographic outcomes of patients who received stent placement for
      spontaneous cervico-cranial arterial dissection. METHODS: We reviewed clinical
      and angiographic data of consecutive patients with spontaneous, cervico-cranial
      arterial dissection treated with stent placement. Patients with recurrent
      ischemic symptoms or severe hemodynamic compromise despite maximal medical
      therapy, or those with compressive symptoms due to expanding pseudoaneurysms were
      considered for stent placement. Follow-up angiography and intravascular
      ultrasound (in select patients) was performed to detect in-stent restenosis,
      intimal flap, thrombus, or persistent pseudoaneurysm. RESULTS: A total of 14
      patients were identified, with complete resolution of stenosis achieved in 10
      patients immediately post-procedure. Clinical follow-up ranged from 26-900 days,
      during which there was 1 (7%) TIA, 1 (7%) minor ischemic stroke, and 1 (7%) in
      hospital death (unrelated to stent placement). Stroke-free survival was 93% at
      both 1 month and 6 months after the procedure. Follow-up angiography did not
      reveal any in-stent restenosis. CONCLUSIONS: This study demonstrates the
      feasibility, safety, and intermediate term effectiveness of endovascular stent
      reconstruction of spontaneous, cervico-cranial arterial dissection.

PMID- 22612243
TI  - Efficacy of systematic pelvic lymphadenectomy in patients with non-endometrioid
      endometrial cancers: a retrospective, multicenter study in Korea.
AB  - AIM: Non-endometrioid endometrial cancer is a clinically and pathologically
      distinct subtype of endometrial cancer. The aim of this study was to determine
      whether systematic pelvic lymphadenectomy improves overall survival compared to
      no lymphadenectomy in non-endometrioid endometrial cancer. MATERIAL AND METHODS:
      The authors retrospectively reviewed the medical records and pathological
      findings of 112 patients who underwent surgical staging for non-endometrioid
      endometrial cancer from 2000 to 2006 in Korea. RESULTS: Systematic pelvic
      lymphadenectomy was performed in 71 patients. Pelvic lymph node metastases were
      identified in 31% and 14.6% patients who underwent systematic pelvic
      lymphadenectomy and no lymphadenectomy, respectively. After adjusting for risk
      factors, there was no significant difference in overall survival (odds ratio =
      0.69; 95% confidence interval, 0.29-1.67) between patients who did or did not
      undergo systematic pelvic lymphadenectomy. On multivariate analysis, patients
      with lymph node metastasis had higher risk of death (odds ratio = 3.11; 95%
      confidence interval, 0.97-10.00) than the patients with no lymph node metastasis.
      CONCLUSION: Although systematic pelvic lymphadenectomy did not affect overall
      survival in patients with the non-endometrioid subtype, it has the potential
      benefit of providing prognostic information and acting as a guide for further
      adjuvant treatment.

PMID- 22612244
TI  - Open reduction and internal fixation better than percutaneous plate
      osteosynthesis in distal tibial fractures.
AB  - Minimally invasive percutaneous plate osteosynthesis (MIPPO) was compared with
      traditional open reduction and internal fixation (ORIF) in treating distal tibial
      fractures. Patients diagnosed with displaced extraarticular distal tibial
      fractures during October 2005-June 2007 were randomly assigned to a closed
      (treated using MIPPO) and an open (treated using ORIF) group. Ninety-four
      patients with fractures were treated and followed up, of which 42 and 52 patients
      were enrolled in the open and closed groups, respectively. The 94 fracture cases
      were classified into three types: Type A, 52 (55.3%); Type B, 24 (25.5%); and
      Type C, 18 (19.1%). The average follow-up time was 15.6 and 16.2 months for the
      open and closed groups, respectively. In the open group, 35 fractures healed
      within six months. Delayed union was observed in three fractures and nonunion in
      four fractures. Two cases had superficial wound infection after operation. No
      malunion was observed. In the closed group, 47 fractures healed within six
      months. Delayed union was observed in four fractures. Locking plate was broken
      nine months after operation in one case. Malunion was observed in five cases: two
      rotational and three posterior angular deformities. No statistically significant
      differences were observed in the healing time of Types A and B between the open
      and closed groups (p > .05). The healing time of Type C in the open group was
      longer than that in the closed group (p < .05). The first choice for Type C
      fractures is MIPPO, whereas that for Type A is open reduction.

PMID- 22612245
TI  - Atmospheric freeze drying for the reduction of powder electrostatics of
      amorphous, low density, high surface area pharmaceutical powders.
AB  - Amorphous itraconazole (ITZ) was prepared by Thin Film Freezing (TFF) utilizing
      1,4-dioxane as the solvent with subsequent solvent removal via conventional tray
      lyophilization (ITZ LYO) or atmospheric freeze drying (ITZ AFD). ITZ AFD was
      prepared under various drying conditions to assess the influence of drying
      parameters on powder properties. XRD analysis confirmed all products were
      amorphous and DSC analysis revealed both drying processes resulted in the
      formation of the nematic mesophase of ITZ. SEM revealed a larger pore size and
      agglomerate size with fewer fine particles (i.e. less than 10 microns in
      diameter) for ITZ AFD compared to ITZ LYO. Residual solvent analysis revealed a
      primary drying temperature of -10 degrees C resulted in residual solvent levels
      above the acceptable limits set by the International Conference on Harmonization
      as a result of microcollapse. Primary drying temperatures of less than -10
      degrees C resulted in acceptable residual solvent levels. The extent of
      microcollapse did not alter the macrostructure of the resulting powder. Powder
      flowability was determined to be similar for ITZ AFD and ITZ LYO based on Carr's
      index and the Hausner ratio, as well as by dynamic angle of repose. All powders
      displayed poor flowability. Chargeability measurements demonstrated a lower
      charge transfer for ITZ AFD powders compared to ITZ LYO due to a combination of
      factors including differences in residual solvent level, particle size, pore
      size, surface area, and fine particles content. The reduction in chargeability as
      a result of AFD is highly desirable because it allows for improved powder
      handling and use post-production.

PMID- 22612246
TI  - Delicate analysis of post-translational modifications on Dishevelled 3.
AB  - The Wnt/beta-catenin signaling pathway plays a critical role in multiple
      developmental events during embryogenesis and adult tissue homeostasis.
      Dishevelled (Dvl) is an important component of Wnt/beta-catenin signaling
      pathway, although the modification, especially phosphorylation, seems closely
      related to the activity and stability of Dvl, the overall modification status of
      Dvl is still poorly understood. In this study, we focused on low abundant Dvl3,
      one of the three Dvl isoforms. Using affinity purification of different sources
      of Dvl3, followed by digestion with both trypsin and chymotrypsin, we
      systematically analyzed the overall modification status of Dvl3 with liquid
      chromatography coupled LTQ-Orbitrap. Altogether, we confidently identified Dvl3
      with more than 50% sequence coverage, including 6 phosphorylation, 4 methylation,
      and 1 dimethylation sites. Most of the identified modification sites were novel
      and located in the linker region between different motifs. Subsequently, the
      validity of modified peptides was confirmed by synthetic modified peptides.
      Finally, SRM analysis was performed to verify and quantify the successive change
      of one dimethylation site on Dvl3 in vivo during Wnt signaling. Taken together,
      our study elucidated the existence of a novel post-translational modification on
      Dvl3 and provided a delicate experimental procedure for analysis of modification
      on low abundant proteins.

PMID- 22612247
TI  - Anomalous size dependence of the thermal conductivity of graphene ribbons.
AB  - We investigated the thermal conductivity K of graphene ribbons and graphite slabs
      as the function of their lateral dimensions. Our theoretical model considered the
      anharmonic three-phonon processes to the second-order and included the angle
      dependent phonon scattering from the ribbon edges. It was found that the long
      mean free path of the long-wavelength acoustic phonons in graphene can lead to an
      unusual nonmonotonic dependence of the thermal conductivity on the length L of a
      ribbon. The effect is pronounced for the ribbons with the smooth edges
      (specularity parameter p > 0.5). Our results also suggest that, contrary to what
      was previously thought, the bulk-like three-dimensional phonons in graphite make
      a rather substantial contribution to its in-plane thermal conductivity. The
      Umklapp-limited thermal conductivity of graphite slabs scales, for L below ~30
      MUm, as log(L), while for larger L, the thermal conductivity approaches a finite
      value following the dependence K(0) - A * L(-1/2), where K(0) and A are
      parameters independent of the length. Our theoretical results clarify the scaling
      of the phonon thermal conductivity with the lateral sizes in graphene and
      graphite. The revealed anomalous dependence K(L) for the micrometer-size graphene
      ribbons can account for some of the discrepancy in reported experimental data for
      graphene.

PMID- 22612248
TI  - Analysis of stored and transplanted cord blood units from KoreaCORD: reappraisal
      of banking guidelines and selection strategy.
AB  - BACKGROUND: We analyzed the characteristics of stored and transplanted cord blood
      (CB) units from the Korean network for public CB donation (KoreaCORD) to reassess
      the banking guidelines and optimize CB selection based on cell dose and human
      leukocyte antigen (HLA) mismatching. STUDY DESIGN AND METHODS: We retrospectively
      reviewed data, with regard to total nucleated cell (TNC) count and HLA match in
      the KoreaCORD registry from August 2001 to December 2010. RESULTS: A total of
      21,914 CB units have been registered, of which 904 units (4.1%) contained less
      than 5 * 10(8)  TNCs, which did not meet the present storage criteria for public
      CB banking in Korea. Although the proportion of stored CBs providing TNC of 5 *
      10(8)  to 7.9 * 10(8)  was 45.7%, only 22.0% of all transplanted CBs were derived
      from these stored CBs. In the single CB transplantation setting, 79% (85/108) of
      CB units provided 4 * 10(7)  TNCs/kg or more in the transplanted one-mismatch (1
      MM) CB units and 51% (19/37) of CBs provided 6 * 10(7)  TNCs/kg or more in the
      transplanted 2-MM CB units. CONCLUSIONS: The minimal requirement of TNCs for
      banking of CB units for public banking should be evaluated and increased to
      support the selection of CB units with higher cell doses, especially for use in
      the 1- and 2-MM transplant settings.

PMID- 22612249
TI  - The combinatorial effect of different Equex STM paste concentrations,
      cryoprotectants and the straw-freezing methods on the post-thaw boar semen
      quality.
AB  - This study was to evaluate the combinatorial effect (14 treatments, A-N) of
      different Equex STM paste concentrations, cryoprotectants and the straw-freezing
      method on the post-thaw boar semen quality. Two ejaculates were collected from
      each of nine boars (three boars from each of three breeds). Semen was diluted in
      extenders with different concentrations of Equex STM paste and different
      cryoprotectants [glycerol or dimethylacetamide (DMA)] before cryopreserving via
      liquid nitrogen or dry ice. Motility, viability, percentage of spermatozoa with
      intense acrosomal staining and with normal morphology of post-thaw sperm were
      evaluated. The qualities of thawed semen were best preserved in treatment H
      (extender with 0.5% Equex STM paste and 5% glycerol and freezing by dry ice) and
      were worst in treatment B (extender with 0% Equex STM paste and 5% DMA and
      freezing by dry ice). Significant difference (p < 0.05) was present in post
      thawed sperm motility (63% vs 27%), sperm viability (70% vs 33%) and sperm
      acrosomal integrity rate (68% vs 29%) between treatments H and B. However, sperm
      proportion with normal morphology showed no significant difference among
      treatments (66% vs 66%; p > 0.05). Moreover, statistical analysis suggests that
      no significant difference was present in semen quality among breed or individual
      donors (p > 0.05). These findings suggest that Equex STM paste improved the
      cryosurvival efficiency of boar sperm, and the favourable straw-freezing method
      changes between glycerol and DMA.

PMID- 22612250
TI  - Transient apical ballooning accompanying respiratory infection.
AB  - We report the case of a 75-year-old man, referred for worsening dyspnea and
      fever. The electrocardiography (ECG) showed mild ST-elevation in anterior leads,
      while cardiac echography severe left ventricular (LV) systolic dysfunction with
      apical ballooning. Later on, ECG showed negative T-waves and QT-prolongation in
      the same anterior leads and T-waves positivization during fever peak. Ten days
      later, LV ejection fraction completely recovered, apical ballooning and fever
      disappeared. We, therefore, hypothesize that transient apical ballooning found in
      our patient may have been induced by a respiratory infection, not detectable at
      seriate blood cultures.

PMID- 22612251
TI  - Controllable fabrication of patterned ZnO nanorod arrays: investigations into the
      impacts on their morphology.
AB  - Fabricating ZnO nanorod arrays with precisely controlled morphology, alignment,
      and density is highly desirable but rather challenging. On the other hand,
      understanding the parameters that affect their final morphology and the growth
      mechanisms is significant to integrate such patterned ZnO nanorod arrays in
      various applications. Therefore, ZnO nanorod arrays with different density and
      morphology were fabricated by electron beam lithography (EBL) combined with the
      hydrothermal methods in this work. The influences of prepatterned geometry and
      the growth parameters such as seed layer, the precursor concentration, and the
      growth time on their final morphology were investigated. Under the coactions of
      EBL and the subsequent hydrothermal growth, ZnO nanorod arrays with precisely
      controlled density, position and morphology were achieved. The growth mechanism
      was also discussed in detail for the ZnO nanorod arrays which confined by the
      aperture with different size. 

PMID- 22612252
TI  - Prospective changes in alcohol use among hazardous drinkers in the absence of
      treatment.
AB  - Gaining a better understanding of the natural course of hazardous alcohol
      consumption could inform the development of brief interventions to encourage self
      change. In the current study, hazardous drinkers (based on Alcohol Use Disorders
      Identification Test score) were recruited using advertisements to participate in
      a 2-year multiwave prospective study. Participants (n = 206) provided self
      reports every six months during the study, including reports of daily alcohol
      consumption. The current investigation focuses on self-initiated change in
      participants' frequency of heavy drinking days (i.e., >= 5/4 drinks per day for
      men/women), as predicted by a number of demographic (e.g., age) and psychosocial
      (e.g., guilt-proneness) variables. Latent growth curve models of the change in
      percent heavy drinking days over the 2-year period provided an excellent fit to
      the observed data and indicated a significant decline in percent heavy drinking
      days over time. Reductions in heavy drinking frequency were predicted by younger
      age and higher guilt-proneness. The identification of these predictors of
      reductions in heavy drinking frequency provides information to guide future work
      investigating self-change among hazardous drinkers.

PMID- 22612253
TI  - The influence of marijuana and alcohol use on condom use behavior: findings from
      a sample of young adult female bar drinkers.
AB  - Prevalence data indicate that alcohol and marijuana are frequently used
      intoxicants among young adults in the United States. In a number of studies, both
      alcohol use and marijuana use have been associated with failure to use condoms, a
      high-risk sexual behavior. The purpose of the current study was to assess the
      individual and additive effects of alcohol and marijuana use on this risky sexual
      behavior among 251 young adult, female bar drinkers. Multilevel modeling was used
      to assess the likelihood of condom use during sexual events that occurred as a
      function of substance use (none, only alcohol, only marijuana, or both) prior to
      and partner type (known or casual) during the event, as well as individual
      differences in sexual assertiveness. Initial model testing (Levels 1 and 2)
      revealed that there were significant main effects for partner type (known),
      substance use (alcohol and marijuana) and sexual assertiveness (refusal,
      pregnancy/STI prevention) on risky sex. Final model testing indicated that sexual
      assertiveness interacted with substance use to influence risky sex. Women who
      were low in sexual assertiveness refusal were more likely to engage in risky sex
      on days when they had consumed both alcohol and marijuana prior to the sexual
      activity. These findings highlight the complex nature of the relationship between
      substance use and risky sex.

PMID- 22612254
TI  - Brief motivational intervention for college drinking: the synergistic impact of
      social anxiety and perceived drinking norms.
AB  - Despite the efficacy of Brief Alcohol Screening and Intervention for College
      Students (BASICS), students with higher social anxiety appear vulnerable to
      poorer outcomes. A possible explanation for these outcomes is that corrective
      normative feedback (an active component of BASICS) may be less effective for
      socially anxious students if their beliefs about others' drinking are less
      malleable because of intense fear of negative evaluation for deviating from
      perceived drinking norms. This study evaluated whether socially anxious students
      demonstrated less change in perceived norms during BASICS. We also examined
      whether change in norm endorsement moderated the relation between social anxiety
      and BASICS outcomes. Undergraduates (n = 52) who underwent BASICS completed
      measures of drinking, social anxiety, and perceived norms at baseline and 4 weeks
      post-BASICS. Higher social anxiety was related to less change in norm endorsement
      after receiving BASICS. Change in perceived norms during treatment moderated the
      relation between social anxiety and follow-up drinking. Among students with
      smaller change in norm endorsement after BASICS, higher social anxiety was
      related to heavier follow-up drinking. Among students with greater changes to
      norm endorsement during BASICS, the effect of social anxiety was nonsignificant.
      Results suggest that corrective perceived norms interventions may be less
      effective among socially anxious students, contributing to continued heavy
      drinking. Development of social anxiety-specific BASICS components warrants
      attention.

PMID- 22612255
TI  - The assessment of protective behavioral strategies: comparing prediction and
      factor structures across measures.
AB  - Protective behavioral strategies (PBS), or drinking control strategies, are
      specific behaviors one can utilize to minimize the harmful consequences of
      alcohol consumption. As there is not currently a standard measure of PBS, the
      goal of the present study was to examine the factor structure and concurrent
      validity of three scales designed to assess PBS: Protective Behavioral Strategies
      Scale (PBSS; Martens, M. P., Ferrier, A. G., Sheehy, M. J., Corbett, K.,
      Anderson, D. A., & Simmons, A., 2005 Development of the Protective Behavioral
      Strategies Survey. Journal of Studies on Alcohol, 66, 698-705), Protective
      Behavioral Strategies Measure (Novik, M. G., & Boekeloo, B. O., 2011,
      Dimensionality and psychometric analysis of an alcohol protective behavioral
      strategies scale. Journal of Drug Education, 41, 65-78. doi:10.2190/DE.41.1.d),
      and the Strategy Questionnaire (SQ); (Sugarman, D. E., & Carey, K. B., 2007), The
      relationship between drinking control strategies and college student alcohol use.
      Psychology of Addictive Behaviors, 21, 338-345. doi:10.1037/0893-164X.21.3.338).
      In a sample of college students (n=291), we used confirmatory factor analysis to
      examine the proposed factor structures of each scale. Although the theorized
      three-factor structure fit the data moderately well for the PBSS, the theorized
      factor structures for the Protective Behavioral Strategies Measure and SQ did not
      fit the data well. Further, the composite scores from the PBSS were all
      significantly negatively correlated with alcohol-related problems, whereas the
      composites of the SQ were not significantly correlated with alcohol-related
      problems. Although we have evidence in favor of 1 PBS measure over others, we
      discuss broader issues related to assessment of PBS. We consider the different
      instructions, response scales, and time intervals for various PBS measures in
      terms of how they relate to the advancement of PBS research.

PMID- 22612256
TI  - Cell-selective gene silencing in prostate cancer LNCap cells using prostate
      specific membrane antigen promoter and enhancer in vitro and in vivo.
AB  - RNAi (RNA interference) has been widely used to silence specific genes. However,
      RNAi may also cause off-target silencing and elicit non-specific side effects. To
      achieve cell-specific gene silencing, a cell-selective promoter has to be used to
      drive RNAi expression. Furthermore, different terminators of cell-selective
      promoters may cause different silencing efficacies. In order to explore the best
      promoter and terminator combination and prove the cell-selective gene silencing
      effect of PSMAe/p (prostate-specific membrane antigen enhancer/promoter), we
      first constructed three plasmids by using PSMAe/p and three different terminators
      [poly(A), minipoly(A) and poly(U)] to explore the cell-selective driving ability
      of PSMAe/p by targeting EGFP (enhanced green fluorescent protein) in LNCaP, PC-3,
      EJ and HEK-293 (human embryonic kidney) cells. Then we chose NS (nucleostemin),
      an important endogenous gene of prostate cancer, and constructed the NS-targeting
      shRNA (small-hairpin RNA) expression plasmid by using PSMAe/p-poly(A)
      combination. Cell proliferation, cell cycle and early apoptosis in vitro and
      xenograft tumour growth in BALB/c nude mice in vivo were detected after NS
      knockdown. Results showed that PSMAe/p can drive EGFP silencing in LNCaP, not in
      PC-3, EJ and HEK-293 cells and PSMAe/p-poly(A) combination achieved the best
      silencing efficacy. Then PSMAe/p-shNS-poly(A) drives NS knockdown in LNCaP cells,
      not in PC-3, EJ and HEK-293 cells. Furthermore, RNAi-mediated NS knockdown not
      only reduces cell proliferation rate, reduces the percentage of S-stage cells and
      increases the percentage of G1-stage cells and increases the early apoptosis
      ratio in LNCaP cells in vitro, but also inhibited the LNCaP xenograft tumour
      growth in BALB/c nude mice in vivo by intratumoural injection. In conclusion, we
      have demonstrated that PSMAe/p-poly(A) combination is a promising delivery system
      for targeted RNAi gene therapy of prostate cancer. We showed one effective
      antitumour strategy by targeting NS protein, an important target in prostate
      cancer, with PSMAe/p-shNS-poly(A). These results serve as an important step for
      developing novel strategies to treat prostate cancer.

PMID- 22612257
TI  - Targeted next generation sequencing as a diagnostic tool in epileptic disorders.
AB  - PURPOSE: Epilepsies have a highly heterogeneous background with a strong genetic
      contribution. The variety of unspecific and overlapping syndromic and
      nonsyndromic phenotypes often hampers a clear clinical diagnosis and prevents
      straightforward genetic testing. Knowing the genetic basis of a patient's
      epilepsy can be valuable not only for diagnosis but also for guiding treatment
      and estimating recurrence risks. METHODS: To overcome these diagnostic
      restrictions, we composed a panel of genes for Next Generation Sequencing
      containing the most relevant epilepsy genes and covering the most relevant
      epilepsy phenotypes known so far. With this method, 265 genes were analyzed per
      patient in a single step. We evaluated this panel on a pilot cohort of 33 index
      patients with concise epilepsy phenotypes or with a severe but unspecific seizure
      disorder covering both sporadic and familial cases. KEY FINDINGS: We identified
      presumed disease-causing mutations in 16 of 33 patients comprising sequence
      alterations in frequently as well as in less commonly affected genes. The
      detected aberrations encompassed known and unknown point mutations (SCN1A
      p.R222X, p. E289V, p.379R, p.R393H; SCN2A p.V208E; STXBP1 p.R122X; KCNJ10 p.L68P,
      p.I129V; KCTD7 p.L108M; KCNQ3 p.P574S; ARHGEF9 p.R290H; SMS p.F58L; TPP1 p.Q278R,
      p.Q422H; MFSD8 p.T294K), a putative splice site mutation (SCN1A c.693A>
      p.T/P231P) and small deletions (SCN1A p.F1330Lfs3X [1 bp]; MFSD8 p.A138Dfs10X [7
      bp]). All mutations have been confirmed by conventional Sanger sequencing and,
      where possible, validated by parental testing and segregation analysis. In three
      patients with either Dravet syndrome or myoclonic epilepsy, we detected SCN1A
      mutations (p.R222X, p.P231P, p.R393H), even though other laboratories had
      previously excluded aberrations of this gene by Sanger sequencing or high
      resolution melting analysis. SIGNIFICANCE: We have developed a fast and cost
      efficient diagnostic screening method to analyze the genetic basis of epilepsies.
      We were able to detect mutations in patients with clear and with unspecific
      epilepsy phenotypes, to uncover the genetic basis of many so far unresolved cases
      with epilepsy including mutation detection in cases in which previous
      conventional methods yielded falsely negative results. Our approach thus proved
      to be a powerful diagnostic tool that may contribute to collecting information on
      both common and unknown epileptic disorders and in delineating associated
      phenotypes of less frequently mutated genes.

PMID- 22612258
TI  - Treatment of hypergranulation tissue with high potency topical corticosteroids in
      children.
AB  - Hypergranulation is having more granulation tissue than needed to fill a wound
      defect. Some pediatric dermatologists and most dermatologic surgeons will
      encounter this complication during their careers. Associated factors include
      wound site, prolonged inflammation, an imbalance in matrix metalloproteinases,
      and excessive angiogenesis. Reported treatments have included silver nitrate,
      excision, laser ablation, and topical corticosteroids. Our case series supports
      the use of medium- to high-potency topical corticosteroids in the treatment of
      hypergranulation tissue.

PMID- 22612259
TI  - Diagnostic and therapeutic endoscopy in children and adolescents with cancer.
AB  - Chemotherapy regimes in children with cancer often cause gastrointestinal side
      effects. Only limited data exist on the use of endoscopy in this group of
      patients. METHODS: Retrospective review over a time period of 8.5 years
      identified 57 endoscopies (49 upper endoscopies, four colonoscopies, three
      sigmoidoscopies, one rectoscopy) in 38 patients (mean age 12.8 years). Seventeen
      children (45%) had hematological malignancies and 21 (55%) had solid tumors. In
      12 children, platelet count was <50 * 10(9)/L and 10 children were neutropenic
      (ANC < 1 * 10(9)/L; absolute neutrophil count). RESULTS: Forty diagnostic
      endoscopies, seven follow-up endoscopies, and 10 therapeutic endoscopies were
      performed. Biopsies were taken in 30 (75%) of 40 diagnostic endoscopies and
      microbiology samples in 17 (42.5%). Pathological findings identified in 33
      (82.5%) diagnostic endoscopies: esophagitis 15 (37.5%)-two of them infections: 1
      candida, 1 HSV (herpes simplex virus); Mallory-Weiss tears 5 (12.5%); gastritis
      18 (45%; four Helicobacter pylori positive); ulcer 1 (2.5%); duodenitis 11
      (27.5%); neoplasia 3 (7.5%); and colitis 5 (12.5%). Therapeutic endoscopies: Four
      PEG (percutaneous endoscopic gastrostomy) tube placements, one tube removal, two
      sclerotherapies for esophageal varices, three nasojejunal tubes for enteral
      nutrition (EN), and three additional tubes in primary diagnostic endoscopies.
      COMPLICATIONS: One episode of fever (>38.5 degrees C) after colonoscopy, one
      localized infection after PEG tube placement, and two episodes of temporary
      desaturation. No association of neutropenia with more infections was observed. No
      bleeding in thrombocytopenic patients was observed. CONCLUSION: The data show
      that endoscopy in high-risk pediatric patients with malignant diseases is a safe
      procedure. Endoscopy reveals relevant information and have therapeutic impact
      with high probability. Tube placement techniques can help to maintain EN.

PMID- 22612260
TI  - Water flows in the Spanish economy: agri-food sectors, trade and households diets
      in an input-output framework.
AB  - Seeking to advance our knowledge of water flows and footprints and the factors
      underlying them, we apply, on the basis of an extended 2004 Social Accounting
      Matrix for Spain, an open Leontief model in which households and foreign trade
      are the exogenous accounts. The model shows the water embodied in products bought
      by consumers (which we identify with the Water Footprint) and in trade
      (identified with virtual water trade). Activities with relevant water inflows and
      outflows such as the agrarian sector, textiles, and the agri-food industry are
      examined in detail using breakdowns of the relevant accounts. The data reflect
      only physical consumption, differentiating between green and blue water. The
      results reveal that Spain is a net importer of water. Flows are then related to
      key trading partners to show the large quantities involved. The focus on embodied
      (or virtual) water by activity is helpful to distinguish indirect from direct
      consumption as embodied water can be more than 300 times direct consumption in
      some food industry activities. Finally, a sensitivity analysis applied to changes
      in diets shows the possibility of reducing water uses by modifying households'
      behavior to encourage healthier eating.

PMID- 22612262
TI  - In response.

PMID- 22612261
TI  - Economic modeling of new stent platforms to evaluate cost effectiveness: analysis
      of the TAXUS Liberte versus TAXUS express stents.
AB  - BACKGROUND: With the changing health care environment, cost effectiveness is an
      important adjunct to clinical investigation when assessing new medical devices.
      This study presents an economic model to evaluate cost effectiveness of coronary
      stents. METHODS: Markov modeling was developed comparing total costs (Medicare
      payer perspective) between TAXUS Liberte and TAXUS Express based on 3-year
      clinical outcomes from the TAXUS ATLAS Small Vessel and Long Lesion trials.
      RESULTS: The TAXUS Liberte 2.25-mm stent provided cost savings relative to TAXUS
      Express from a payer perspective ($17,605 vs. $20,281), driven by reduced target
      vessel revascularization (0.16 events/patient vs. 0.33 events/patient). In
      probabilistic sensitivity analyses, TAXUS Liberte was less costly with fewer
      major adverse cardiac events in over 99% of parameter sets. The TAXUS Liberte
      Long (38 mm) stent was cost neutral relative to TAXUS Express from a payer
      perspective ($18,545 vs. $18,551) with fewer myocardial infarctions and cardiac
      deaths. Accounting for angiography-driven revascularizations, TAXUS Liberte 2.25
      mm still provided cost savings relative to TAXUS Express ($16,822 vs. $19,139),
      although TAXUS Liberte Long was more expensive than TAXUS Express ($17,886 vs.
      $17,652). From a hospital perspective, TAXUS Liberte Long provided cost savings
      up to a price premium of $671/stent, driven by fewer stents employed per patient.
      CONCLUSIONS: This analysis confirms the utility of economic modeling in assessing
      new stent platforms. TAXUS Liberte 2.25 mm is economically dominant relative to
      TAXUS Express when treating small vessels. TAXUS Liberte Long is cost neutral to
      modestly more costly than TAXUS Express 2.25 mm from a payer perspective.

PMID- 22612265
TI  - Kinetics of the C-C bond beta scission reactions in alkyl radical reaction class.
AB  - Kinetics of the beta-scission in alkyl radical reaction class was studied using
      the reaction class transition state theory (RC-TST) combined with the linear
      energy relationship (LER) and the barrier height grouping (BHG) approach. All
      necessary parameters were derived from first-principle density functional
      calculations for a representative set of 21 reactions. Different error analyses
      and comparisons with available literature data were made. Direct comparison with
      available experimental data indicates that the RC-TST/LER, where only reaction
      energy is needed, can predict rate constants for any reaction in this reaction
      class with excellent accuracy. Specifically for this reaction class, the RC
      TST/LER method has less than 60% systematic errors on average in the predicted
      rate constants when compared to explicit rate calculations.

PMID- 22612264
TI  - Catalytic asymmetric synthesis of secondary nitriles via stereoconvergent Negishi
      arylations and alkenylations of racemic alpha-bromonitriles.
AB  - The first method for the stereoconvergent cross-coupling of racemic alpha
      halonitriles is described, specifically, nickel-catalyzed Negishi arylations and
      alkenylations that furnish an array of enantioenriched alpha-arylnitriles and
      allylic nitriles, respectively. Noteworthy features of this investigation
      include: the highly enantioselective synthesis of alpha-alkyl-alpha-aryl nitriles
      that bear secondary alpha-alkyl substituents; the first examples of the use of
      alkenylzinc reagents in stereoconvergent Negishi reactions of alkyl
      electrophiles; demonstration of the utility of a new family of ligands for
      asymmetric Negishi cross-couplings (a bidentate bis(oxazoline), rather than a
      tridentate pybox); in the case of arylzinc reagents, carbon-carbon bond formation
      at a remarkably low temperature (-78  degrees C), the lowest reported to date for
      an enantioselective cross-coupling of an alkyl electrophile; a mechanistic
      dichotomy between Negishi reactions of an unactivated versus an activated
      secondary alkyl bromide.

PMID- 22612266
TI  - Antioxidant capacities of phlorotannins extracted from the brown algae Fucus
      vesiculosus.
AB  - A process for the effective extraction and fractionation of phlorotannins from
      Fucus vesiculosus with high antioxidant potentials was investigated. The
      antioxidant activity of F. vesiculosus extract/fractions was assessed by 2,2
      diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, reducing power, and ferrous
      ion-chelating assays. Among the crude extract and different polarity fractions,
      the phlorotannin-enriched ethyl acetate fraction possessed the highest DPPH
      scavenging activity and reducing power. This fraction was further fractionated by
      Sephadex LH-20 column chromatography or ultrafiltration. The antioxidant
      properties were evaluated by both the above chemical antioxidant tests and a
      mononuclear cell-based bioassay. Sephadex subfractions LH-2 and LH-3 with high
      total phlorotannin content exhibited strong DPPH quenching activity, comparable
      to those of ascorbic acid and butylated hydroxytoluene and significantly higher
      than that of alpha-tocopherol. Polyphenols in F. vesiculosus were found to
      consist mainly of high molecular weight phlorotannin polymers. There were no
      clear relationships between the degree of polymerization, molecular size, and
      antioxidant activity. All the subfractions separated by Sephadex LH-20 column
      chromatography and ultrafiltration showed a high ability to scavenge reactive
      oxygen species generated by mononuclear cells. Further characterization of the
      phlorotannin compounds was performed on six Sephadex subfractions. Several
      phlorotannin oligomers were tentatively identified on the basis of HPLC-ESI-MS(n)
      analyses. 

PMID- 22612267
TI  - Effective management of severe traumatic brain injury in a district hospital.
AB  - The authors investigated how effectively adults with severe traumatic brain
      injury (TBI) can be managed in a district general hospital intensive care unit
      offering intracranial pressure monitoring (ICPM) receiving advice from a
      neurosurgical unit. A single-centre case series with retrospective review of
      prospectively collected information was undertaken of 44 consecutive patients
      presenting over seven years from January 2003 to January 2010 with severe
      traumatic brain injury to a single district general hospital intensive care unit
      serving a population of 500,000 adults. A prospectively entered clinical database
      was used to obtain information including patient demographics, Glasgow Coma Score
      (GCS) on admission, ICPM insertion, ICPM-related complications, inpatient
      mortality and neurosurgical advice. Case notes were used to ratify information
      and obtain neurorehabilitation clinic functional outcome scores. Forty-four
      patients were identified (40 male, age range 16-77 years). Mortality in intensive
      care was 30%. Twenty-eight patients received frontal twist drill ICPM following
      neurosurgical advice. ICPM had 2 (7%) device malfunctions but no other
      complications. Twelve additional patients were transferred to tertiary centres.
      Patients (23 of 31) who survived ICU stay (74%) were referred to
      neurorehabilitation. Mean clinic follow-up was 14 months. All patients had a
      Glasgow Outcome Score (GOS) of 3 or 4 at initial clinic assessment. Twenty-two
      improved to GOS to 4 or 5 at clinic discharge. One patient died prior to clinic
      discharge. Carefully selected patients with severe TBI can be managed safely and
      effectively in a district general hospital offering ICPM insertion if transfer to
      a neurosurgical centre is not possible. Neurosurgical advice regarding patient
      selection and on-going management is fundamental to provide a good service.
      Protocol driven therapies provide a useful systematic approach to doctors who do
      not deal with severe TBI on a routine basis.

PMID- 22612268
TI  - Ligand binding stepwise disrupts water network in thrombin: enthalpic and
      entropic changes reveal classical hydrophobic effect.
AB  - Well-ordered water molecules are displaced from thrombin's hydrophobic S3/4
      pocket by P3-varied ligands (Gly, d-Ala, d-Val, d-Leu to d-Cha with increased
      hydrophobicity and steric requirement). Two series with 2-(aminomethyl)-5
      chlorobenzylamide and 4-amidinobenzylamide at P1 were examined by ITC and
      crystallography. Although experiencing different interactions in S1, they display
      almost equal potency. For both scaffolds the terminal benzylsulfonyl substituent
      differs in binding, whereas the increasingly bulky P3-groups address S3/4 pocket
      similarly. Small substituents leave the solvation pattern unperturbed as found in
      the uncomplexed enzyme while increasingly larger ones stepwise displace the
      waters. Medium-sized groups show patterns with partially occupied waters. The
      overall 40-fold affinity enhancement correlates with water displacement and
      growing number of van der Waals contacts and is mainly attributed to favorable
      entropy. Both Gly derivatives deviate from the series and adopt different binding
      modes. Nonetheless, their thermodynamic signatures are virtually identical with
      the homologous d-Ala derivatives. Accordingly, unchanged thermodynamic profiles
      are no reliable indicator for conserved binding modes.

PMID- 22612270
TI  - Myeloma crystal tubulopathy and Fanconi syndrome: a rare histological finding.

PMID- 22612269
TI  - Comparison of abdominal computed tomography and abdominal ultrasound in sedated
      dogs.
AB  - Abdominal ultrasound (US) is used frequently as a first-line screening tool for
      abdominal disease. Although computed tomography (CT) is superior to US in the
      diagnosis of some abdominal diseases, a major impediment is the requirement of
      general anesthesia to prevent motion and for safe restraint. With multidetector
      helical CT, faster examinations allow general anesthesia to be avoided, while
      producing diagnostic-quality images. Abdominal US and CT were compared for lesion
      detection in 27 sedated dogs, divided into three even groups based on body
      weight. Lesions were categorized further as to subjective clinical relevance. In
      dogs less than 25 kg, there is no significant difference in lesion detection
      between CT and US. In dogs weighing greater than 25 kg, more lesions were
      detected with CT than with US (P = 0.0001), including clinically relevant lesions
      (P = 0.0277). From these results, it appears that CT has an advantage in lesion
      detection in dogs greater than 25 kg, making it a better screening test for
      abdominal disease in these patients.

PMID- 22612271
TI  - Vaginal evisceration 3 years after abdominal hysterectomy and bilateral salpingo
      oophorectomy.
AB  - Vaginal evisceration after a pelvic operation is a rare gynecological emergency.
      When intercourse is the cause, most cases occur within 1 year of surgery. A 53
      year-old woman presented to the emergency room for vaginal evisceration half a
      day after the first postoperative occurrence of intercourse 3 years after an
      abdominal hysterectomy and bilateral salpingo-oophorectomy. In an emergency
      laparotomy, the protruding small bowel was replaced within the abdominal cavity.
      The avulsed vaginal cuff, which measured 6 cm in length and had atrophic but non
      necrotic margins, was sutured. Women who go for long periods without intercourse
      after a hysterectomy, especially post-menopausal women, should be made aware of
      unrecognized vaginal atrophy that could, in some cases, lead to rupture and
      evisceration during the next occurrence of intercourse.

PMID- 22612272
TI  - Long noncoding RNA: its physiological and pathological roles.
AB  - Long noncoding RNAs (lncRNAs) are transcribed RNA molecules >200 nucleotides in
      length. They comprise a diverse class of transcripts that structurally resemble
      mRNAs, but do not encode proteins. The characterization of lncRNAs and their
      acceptance as crucial regulators of numerous developmental and biological
      pathways have suggested that the lncRNA study has gradually become one of the hot
      topics in the field of RNA biology. In this article, we will highlight recent
      progress regarding lncRNAs studies, including their classification, biological
      functional characterization, and their potential roles in disease development.

PMID- 22612273
TI  - Indolent CD8-positive T-cell lymphoid proliferation of the ear: a report of two
      cases.
AB  - The current classification of primary cutaneous T-cell lymphoma (CTCL) of the
      World Health Organization (WHO) includes primary cutaneous CD8-positive
      aggressive epidermotropic cytotoxic T-cell lymphoma as a provisional entity
      awaiting cumulative data. Recent reports identify CD3/CD8-positive clonal T-cell
      lymphoid proliferations arising in the ear and nose that behave indolently and
      therefore defy currently established subclassification. Here, we report two cases
      of clonal CD8-positive/granzyme-B-negative T-cell lymphoid proliferations that
      arose in the ear and behaved indolently. Collectively, these cases suggest that
      an additional category of cutaneous indolent CD8-positive T-cell lymphoma may be
      necessary among the existing classification schemes.

PMID- 22612274
TI  - Small deletions within the RHD coding sequence: a report of two novel mutational
      events and a survey of the underlying pathophysiologic mechanisms.
AB  - BACKGROUND: Some 270 variants in the RHD gene have so far been identified. Of
      these, approximately 6% (n = 17) are small (<=20 bp) deletions occurring within
      the gene's coding sequence. Fourteen of these small deletions disrupted the
      reading frame of the RHD gene, resulting almost invariably in a D- phenotype.
      STUDY DESIGN AND METHODS: Two subjects who displayed D phenotype ambiguity or a
      genotype-phenotype discrepancy were referred to our laboratory for RHD genetic
      analysis. Hemizygosity for the most common 70-kb RHD deletion was first
      determined in both subjects by long-range polymerase chain reaction (PCR)
      followed by PCR amplification and sequencing of all 10 exons of the RHD gene in
      the nondeleted allele individually. RESULTS: Two novel lesions in the RHD gene
      were identified on the nondeleted alleles, a 14-bp frameshifting deletion within
      Exon 1 (i.e., c.29_42delGGCGCTGCCTGCCC) and an 11-bp frameshifting deletion
      within Exon 3 (i.e., c.361_371delTTGTCGGTGCT), in Subjects 1 and 2, respectively.
      CONCLUSION: By reference to previously reported small deletions in the RHD gene,
      the 11-bp deletion in Exon 3 may be safely regarded as a bona fide D- variant.
      Although the association of the 14-bp deletion in Exon 1 with a weak D phenotype
      appears to be genuine, the underlying molecular mechanism still remains to be
      clarified. Evaluation of all known small RHD deletions points to slippage
      mutagenesis as the major underlying mutational mechanism. [Correction statement
      added after online publication 21-May2012: The spelling of bona has been
      updated.].

PMID- 22612275
TI  - Endothelial progenitor cell capture stent: safety and effectiveness.
AB  - The endothelial progenitor cell (EPC) capture stent is an innovative device that
      makes use of the ability of bone marrow-derived EPCs to migrate to injured
      arterial segments to facilitate healing. The EPC antibody surface, consisting of
      a covalently coupled polysaccharide intermediate coating with anti-human CD34
      antibodies, is attached to a stainless steel stent. Upon stent placement, the
      anti-human CD34 antibodies will attract circulating EPCs, which are expected to
      develop into mature functional endothelium. This accelerated healing strategy
      aims to lower the risk of restenosis and stent thrombosis, as well as obviate
      prolonged dual antiplatelet therapy. Since the first-in-man study in 2003, a
      number of small-to-medium size registry and postmarketing studies that confirmed
      the good safety profile of the EPC capture stent have been published. However,
      due to lack of large-scale randomized trials, its effectiveness, compared with
      bare metal stents and drug-eluting stents, cannot be ascertained. Based on
      restudy angiographic data, instent late loss was approximately 0.7-0.9 mm, which
      compares unfavorably with that of drug-eluting stents. In order to improve the
      effectiveness of the EPC capture stent in reducing restenosis--while maintaining
      its pro-healing property--a bioengineered sirolimus-eluting stent known as the
      Combo stent was recently designed to combine the EPC capture technology with the
      abluminal elution of sirolimus. Data from animal studies have been encouraging.
      The first-in-man study of the Combo stent has been completed and results were
      presented.

PMID- 22612276
TI  - Magnesium fluctuations modulate RNA dynamics in the SAM-I riboswitch.
AB  - Experiments demonstrate that Mg(2+) is crucial for structure and function of RNA
      systems, yet the detailed molecular mechanism of Mg(2+) action on RNA is not well
      understood. We investigate the interplay between RNA and Mg(2+) at atomic
      resolution through ten 2-MUs explicit solvent molecular dynamics simulations of
      the SAM-I riboswitch with varying ion concentrations. The structure, including
      three stemloops, is very stable on this time scale. Simulations reveal that outer
      sphere coordinated Mg(2+) ions fluctuate on the same time scale as the RNA, and
      that their dynamics couple. Locally, Mg(2+) association affects RNA conformation
      through tertiary bridging interactions; globally, increasing Mg(2+) concentration
      slows RNA fluctuations. Outer-sphere Mg(2+) ions responsible for these effects
      account for 80% of Mg(2+) in our simulations. These ions are transiently bound to
      the RNA, maintaining interactions, but shuttled from site to site. Outer-sphere
      Mg(2+) are separated from the RNA by a single hydration shell, occupying a thin
      layer 3-5 A from the RNA. Distribution functions reveal that outer-sphere Mg(2+)
      are positioned by electronegative atoms, hydration layers, and a preference for
      the major groove. Diffusion analysis suggests transient outer-sphere Mg(2+)
      dynamics are glassy. Since outer-sphere Mg(2+) ions account for most of the
      Mg(2+) in our simulations, these ions may change the paradigm of Mg(2+)-RNA
      interactions. Rather than a few inner-sphere ions anchoring the RNA structure
      surrounded by a continuum of diffuse ions, we observe a layer of outer-sphere
      coordinated Mg(2+) that is transiently bound but strongly coupled to the RNA.

PMID- 22612277
TI  - Microphthalmia with linear skin defects syndrome.
AB  - Microphthalmia with linear skin defects (MLS) or microcornea, dermal aplasia and
      sclerocornea (MIDAS) syndrome is a rare X-linked-dominant disorder. We present a
      patient with agenesis of corpus callosum, ocular abnormalities, and multiple skin
      defects. The cytogenetic studies of the MLS critical region (Xp22.2) were normal,
      but a skewed X-chromosome inactivation pattern (85:15) was observed. 

PMID- 22612278
TI  - Aquatic photochemistry of isoflavone phytoestrogens: degradation kinetics and
      pathways.
AB  - Isoflavones are plant-derived chemicals that are potential endocrine disruptors.
      Although some recent studies have detected isoflavones in natural waters, little
      is known about their aquatic fates. The photochemical behaviors of the
      isoflavones daidzein, formononetin, biochanin A, genistein, and equol were
      studied under simulated solar light and natural sunlight. All of these
      phytoestrogens were found to be photolabile under certain conditions. Daidzein
      and formononetin degraded primarily by direct photolysis. Their expected near
      surface summer half-lives in pH 7 water at 47 degrees  latitude are expected to
      be 10 and 4.6 h, respectively. Biochanin A, genistein, and equol degraded
      relatively slowly by direct photolysis at environmentally realistic pH values,
      though they showed significant degradation rate enhancements in the presence of
      natural organic matter (NOM). The indirect photolysis rates for these compounds
      scaled with NOM concentration, and NOM from microbial origin was found to be a
      more potent photosensitizer than NOM from terrestrial sources. Mechanistic
      studies were performed to determine the indirect photolysis pathways responsible
      for the rate enhancements. Results of these studies implicate reaction with both
      singlet oxygen and excited state triplet NOM. Environmental half-lives for
      biochanin A, genistein, and equol are expected to vary on the basis of pH as well
      as NOM source and concentration.

PMID- 22612279
TI  - Development of pyridine-containing macrocyclic copper(II) complexes: potential
      role in the redox modulation of oxaliplatin toxicity in human breast cells.
AB  - The unique redox and catalytic chemistry of Cu has justified the development of
      novel Cu complexes for different therapeutic uses including cancer therapy. In
      this work, four pyridine-containing aza-macrocyclic copper(II) complexes were
      prepared (CuL1-CuL4) varying in ring size and/or substituents and their
      superoxide scavenging activity evaluated. CuL3, the most active superoxide
      scavenger, was further studied as a modulator of the cytotoxicity of oxaliplatin
      in epithelial breast MCF10A cells and in MCF7 breast cancer cells. Our results
      show that CuL3 enhances the therapeutic window of oxaliplatin, by both protecting
      non-tumour cells and increasing its cytotoxic effect in breast carcinoma cells.
      CuL3 is thus a promising complex to be further studied and to be used as a lead
      compound for the optimization of novel chemotherapy sensitizers.

PMID- 22612280
TI  - Mechanisms of intentional binding and sensory attenuation: the role of temporal
      prediction, temporal control, identity prediction, and motor prediction.
AB  - Sensory processing of action effects has been shown to differ from that of
      externally triggered stimuli, with respect both to the perceived timing of their
      occurrence (intentional binding) and to their intensity (sensory attenuation).
      These phenomena are normally attributed to forward action models, such that when
      action prediction is consistent with changes in our environment, our experience
      of these effects is altered. Although much progress has been made in recent years
      in understanding sensory attenuation and intentional binding, a number of
      important questions regarding the precise nature of the predictive mechanisms
      involved remain unanswered. Moreover, these mechanisms are often not discussed in
      empirical papers, and a comprehensive review of these issues is yet to appear.
      This review attempts to fill this void. We systematically investigated the role
      of temporal prediction, temporal control, identity prediction, and motor
      prediction in previous published reports of sensory attenuation and intentional
      binding. By isolating the individual processes that have previously been
      contrasted and incorporating these experiments with research in the related
      fields of temporal attention and stimulus expectation, we assessed the degree to
      which existing data provide evidence for the role of forward action models in
      these phenomena. We further propose a number of avenues for future research,
      which may help to better determine the role of motor prediction in processing of
      voluntary action effects, as well as to improve understanding of how these
      phenomena might fit within a general predictive processing framework.
      Furthermore, our analysis has important implications for understanding disorders
      of agency in schizophrenia.

PMID- 22612281
TI  - Auditory, tactile, and audiotactile information processing following visual
      deprivation.
AB  - We highlight the results of those studies that have investigated the plastic
      reorganization processes that occur within the human brain as a consequence of
      visual deprivation, as well as how these processes give rise to behaviorally
      observable changes in the perceptual processing of auditory and tactile
      information. We review the evidence showing that visual deprivation affects the
      establishment of the spatial coordinate systems involved in the processing of
      auditory and tactile inputs within the peripersonal space around an individual.
      In blind individuals, the absence of a conjoint activation of external coordinate
      systems across modalities co-occurs with a higher capacity to direct auditory and
      tactile attentional resources to different spatial locations and to ignore
      irrelevant distractors. Both processes could thus contribute to the reduced
      spatial multisensory binding that has been observed in those who are blind. The
      interplay between auditory and tactile information in visually deprived
      individuals is modulated by attentional factors. Blind individuals typically
      outperform sighted people in those tasks where the target is presented in one
      sensory modality (and the other modality acts as a distractor). By contrast, they
      are less efficient in tasks explicitly requiring the combination of information
      across sensory modalities. The review highlights how these behavioral effects are
      subserved by extensive plastic changes at the neural level, with brain areas
      traditionally involved in visual functioning switching and being recruited for
      the processing of stimuli within the intact residual senses. We also discuss the
      roles played by other intervening factors with regard to compensatory mechanisms,
      such as previous visual experience, age at onset of blindness, and learning
      effects.

PMID- 22612283
TI  - Nature of chemical bonding and metalloaromaticity of Na2[(MArx')3] (M = B, Al,
      Ga; Arx' = C6H3-2,6-(C6H5)2).
AB  - The nature of chemical bonding and metalloaromaticity of Na(2)[(MArx')(3)] (M =
      B, Al, Ga) have been studied within the framework of the atoms in molecules (AIM)
      theory and using electron localization function (ELF) analysis. The pi electrons
      of the studied systems were separated from the total electron density and
      analyzed. The calculated results indicate that there are closed-shell weak
      interactions between the sodium atom and the M(3) (M = B, Al, Ga) ring, between
      the sodium atom and the terminal phenyl group on each Arx', and between the
      terminal phenyl groups on Arx' in Na(2)[(MArx')(3)]. The Na(2)[(MArx')(3)] has
      metalloaromatic nature, and the sodium atoms have an active role in determining
      the computed aromatic properties of the three-numbered cycle.

PMID- 22612282
TI  - Optimization of contrast-enhanced multidetector abdominal computed tomography in
      sedated canine patients.
AB  - A major disadvantage of computed tomography for abdominal screening in dogs has
      been the need for general anesthesia to prevent motion artifacts. With
      multidetector helical CT, it is possible to decrease examination time, allowing
      patients to be scanned under sedation. It is also desirable to decrease tube
      loading to prolong x-ray tube life. To develop a protocol that will allow for
      examination of sedated patients with minimal image artifacts, milliamperage (mA)
      and helical pitch were varied, providing 16 experimental scan protocols. A
      standard clinical protocol was also tested, providing 17 protocols for
      evaluation. These protocols were tested, using a standard CT phantom, canine
      tissues in a water bath, and a canine cadaver. The cadaver images were scored
      semiquantitatively by three reviewers to determine the protocol with the best
      combination of speed and minimal image artifact. The optimized protocol was then
      applied to 27 sedated canine patients of three body weight categories. The images
      obtained were compared to the standard protocol by two reviewers for presence of
      motion, streak, and quantum mottle artifacts. There was significantly more streak
      artifact noted by one observer using the optimized study protocol, but no
      significant difference in any other category. Scanning under sedation was well
      tolerated in all patients, and sedated CT examination is a promising tool for
      screening abdominal disease in dogs.

PMID- 22612284
TI  - Trajectories for frontal external ventricular drain placement: virtual
      cannulation of adults with acute hydrocephalus.
AB  - OBJECTIVES: External ventricular drains (EVDs) are commonly placed freehand using
      targeting landmarks unchanged since the pre-CT era; it is known to be an
      inaccurate procedure. To our knowledge, this is the first study to assess the
      geometric reliability of specific trajectories in a three-dimensional model.
      DESIGN: Three-dimensional volume reconstruction of EVD trajectories in a Stealth
      Station S7. SUBJECTS: Adults with a primary EVD sited for acute hydrocephalus
      secondary to spontaneous subarachnoid haemorrhage with CT angiography less than
      24 hours previously. METHODS: CT angiograms from 10 consecutive patients meeting
      the inclusion criteria were reconstructed. The surgical planning tool was used to
      construct three trajectories from Kocher's point: i) perpendicular to the skull
      (PTS) ii) towards the ipsilateral medial canthus coronally and the external
      auditory meatus sagitally (IMC) iii) towards the contralateral medial canthus
      coronally and the external auditory meatus sagitally (CMC). Their engagement with
      the frontal horn of the ipsilateral lateral ventricle (FILV) and distance from
      the ventricular wall and foramen of Monro were measured. RESULTS: Mean
      supratentorial ventricular volume was 55.8 cc (range 35.2-83.4 cc). The IMC met
      the FILV in only one patient, on average missing the ventricular wall by 5.5+/
      2.3 degrees (95% confidence interval). CMC and PTS met the FILV in 9 and 10
      cases, respectively. Mean engagement was 16.3+/-5.1 mm (95% confidence interval)
      for PTS and 20.0+/-7.1 mm (95% confidence interval) for CMC. CMC and PTS gave
      significantly better engagement and aiming error margins than the IMC trajectory.
      CONCLUSIONS: Despite its widespread use, the IMC trajectory performed poorly; PTS
      and CMC trajectories are more reliable ways of targeting the FILV when placing an
      EVD.

PMID- 22612285
TI  - P450-aromatase mRNA is expressed in the corpus luteum (CL) of the non-pregnant
      sheep and goat: the expression of the enzyme is present throughout pregnancy in
      the goat CL.
AB  - In most mammals, the corpus luteum (CL) and placenta are the major sources of
      progesterone. The goat pregnancy depends on the presence of CL after mid
      gestation, while sheep pregnancy does not. The expression and distribution of
      P450-aromatase (P450-Aro) mRNA throughout gestation has not been investigated in
      the goat CL and partially in the sheep CL. The present research was designed to
      characterize the expression of P450-Aro mRNA in small ruminant CL with emphasis
      in the goat. For this purpose, ovaries from Criollo goats and Pelibuey sheeps
      were analysed using in situ reverse transcription-polymerase chain reaction (RT
      PCR) for the histological detection of P450-Aro transcripts. In addition, P450
      Aro expression was determined by in vitro RT-PCR. In situ RT-PCR studies showed
      that the goat and sheep CL were rich in cells positive for P450-Aro mRNA. We have
      also found in vitro RT-PCR expression of P450-Aro mRNA in goat CL at 1, 3 and 4
      months of gestation. This study shows that the goat CL expresses P450-Aro mRNA
      along gestation, suggesting that this structure is capable to produce oestrogens
      up to the end of gestation.

PMID- 22612286
TI  - Granulosa cell tumor of the ovary after long-term use of tamoxifen and
      toremifene.
AB  - The relation between the use of tamoxifen and gynecologic tumors has been
      documented. In this case, a 58-year-old postmenopausal woman had been treated
      with tamoxifen for 5 years followed by toremifene for 1.5 years due to the
      presence of stage II estrogen receptor-positive breast cancer. The patient was
      found to have a stage Ic granulosa cell tumor of the ovary despite undergoing
      annual gynecologic examinations. This report presents a case of granulosa cell
      tumor of the ovary after the long-term use of tamoxifen and toremifene.

PMID- 22612287
TI  - Possible role of exosomes containing RNA in mediating nontargeted effect of
      ionizing radiation.
AB  - Communication between irradiated and un-irradiated (bystander) cells can cause
      damage in cells that are not directly targeted by ionizing radiation, a process
      known as the bystander effect. Bystander effects can also lead to
      chromosomal/genomic instability within the progeny of bystander cells, similar to
      the progeny of directly irradiated cells. The factors that mediate this cellular
      communication can be transferred between cells via gap junctions or released into
      the extracellular media following irradiation, but their nature has not been
      fully characterized. In this study we tested the hypothesis that the bystander
      effect mediator contains an RNA molecule that may be carried by exosomes. MCF7
      cells were irradiated with 2 Gy of X rays and the extracellular media was
      harvested. RNase treatment abrogated the ability of the media to induce early and
      late chromosomal damage in bystander cells. Furthermore, treatment of bystander
      cells with exosomes isolated from this media increased the levels of genomic
      damage. These results suggest that the bystander effect, and genomic instability,
      are at least in part mediated by exosomes and implicate a role for RNA.

PMID- 22612288
TI  - Antivirals targeting influenza A virus.

PMID- 22612289
TI  - Toll-like receptor 4 knockout protects against anthrax lethal toxin-induced
      cardiac contractile dysfunction: role of autophagy.
AB  - BACKGROUND AND PURPOSE: Anthrax lethal toxin (LeTx) is known to induce
      circulatory shock and death, although the underlying mechanisms have not been
      elucidated. This study was designed to evaluate the role of toll-like receptor 4
      (TLR4) in anthrax lethal toxin-induced cardiac contractile dysfunction.
      EXPERIMENTAL APPROACH: Wild-type (WT) and TLR4 knockout (TLR-/-) mice were
      challenged with lethal toxin (2 ug.g-1, i.p.), and cardiac function was assessed
      18 h later using echocardiography and edge detection. Small interfering RNA
      (siRNA) was employed to knockdown TLR4 receptor or class III PI3K in H9C2
      myoblasts. GFP-LC3 puncta was used to assess autophagosome formation. Western
      blot analysis was performed to evaluate autophagy (LC3, Becline-1, Agt5 and Agt7)
      and endoplasmic reticulum (ER) stress (BiP, eIF2alpha and calreticulin). KEY
      RESULTS: In WT mice, lethal toxin exposure induced cardiac contractile
      dysfunction, as evidenced by reduced fractional shortening, peak shortening,
      maximal velocity of shortening/re-lengthening, prolonged re-lengthening duration
      and intracellular Ca2+ derangement. These effects were significantly attenuated
      or absent in the TLR4 knockout mice. In addition, lethal toxin elicited autophagy
      in the absence of change in ER stress. Knockdown of TLR4 or class III PI3 kinase
      using siRNA but not the autophagy inhibitor 3-methyladenine significantly
      attenuated or inhibited lethal toxin-induced autophagy in H9C2 cells. CONCLUSION
      AND IMPLICATIONS: Our results suggest that TLR4 may be pivotal in mediating the
      lethal cardiac toxicity induced by anthrax possibly through induction of
      autophagy. These findings suggest that compounds that negatively modulate TLR4
      signalling and autophagy could be used to treat anthrax infection-induced
      cardiovascular complications.

PMID- 22612290
TI  - Pharmacokinetics and drug interactions of eslicarbazepine acetate.
AB  - Eslicarbazepine acetate (ESL) is a novel once-daily antiepileptic drug (AED)
      approved in Europe since 2009 that was found to be efficacious and well tolerated
      in a phase III clinical program in adult patients with partial onset seizures
      previously not controlled with treatment with one to three AEDs, including
      carbamazepine (CBZ). ESL shares with CBZ and oxcarbazepine (OXC) the
      dibenzazepine nucleus bearing the 5-carboxamide substitute, but is structurally
      different at the 10,11 position. This molecular variation results in differences
      in metabolism, preventing the formation of toxic epoxide metabolites such as
      carbamazepine-10,11-epoxide. Unlike OXC, which is metabolized to both
      eslicarbazepine and (R)-licarbazepine, ESL is extensively converted to
      eslicarbazepine. The systemic exposure to eslicarbazepine after ESL oral
      administration is approximately 94% of the parent dose, with minimal exposure to
      (R)-licarbazepine and OXC. After ESL oral administration, the effective half-life
      (t(1/2,eff) ) of eslicarbazepine was 20-24 h, which is approximately two times
      longer than its terminal half-life (t(1/2)). At clinically relevant doses (400
      1,600 mg/day) ESL has linear pharmacokinetics (PK) with no effects of gender or
      moderate liver impairment. However, because eslicarbazepine is eliminated
      primarily (66%) by renal excretion, dose adjustment is recommended for patients
      with renal impairment. Eslicarbazepine clearance is induced by phenobarbital,
      phenytoin, and CBZ and it dose-dependently decreases plasma exposure of oral
      contraceptive and simvastatin.

PMID- 22612291
TI  - Improved synthesis of C4alpha- and C4beta-methyl analogues of 2
      aminobicyclo[3.1.0]hexane-2,6-dicarboxylate.
AB  - An efficient and divergent synthesis of C4alpha- and C4beta-methyl-substituted
      analogues of 2-aminobicyclo[3.1.0]hexane 2,6-dicarboxylate, which are important
      tools in the study of metabotropic glutamate receptor function, has been
      achieved. By taking advantage of an unanticipated facial selectivity of the
      bicyclo[3.1.0]hexane ring system, either the C4alpha- or C4beta-methyl
      substituent was introduced in a highly stereoselective and high-yielding manner.

PMID- 22612292
TI  - Bone morphogenetic protein 2 inhibits neurite outgrowth of motor neuron-like NSC
      34 cells and up-regulates its type II receptor.
AB  - Bone morphogenetic proteins (BMPs) regulate several aspects of neuronal behavior.
      For instance, BMP-2 has the ability to modulate, either positively or negatively,
      the outgrowth of neuronal processes in diverse cell types. In Drosophila motor
      neurons, the BMP type II receptor (BMPRII) homolog wishful thinking plays crucial
      roles on neuromuscular synaptogenesis signaling through Smad-dependent and Smad
      independent pathways. However, a role for BMP signaling at the vertebrate
      neuromuscular junction has not been addressed. Herein, we have analyzed the
      expression of BMPRII and the effect of BMP-2 during the morphological
      differentiation of motor neuron-like NSC-34 cells. Our data indicate that BMPRII
      is up-regulated and becomes accumulated in somas and growth cones upon motor
      neuronal differentiation. BMP-2 inhibits the differentiation of NSC-34 cells, an
      effect that correlates with activation of a Smad-dependent pathway, induction of
      the inhibitory Id1 transcription factor, and down-regulation of the neurogenic
      factor Mash1. BMP-2 also activates effectors of Smad-independent pathways.
      Remarkably, BMP-2 treatment significantly increases the expression of BMPRII. Our
      findings provide the first evidence to suggest a role for BMP pathways on the
      differentiation of motor neurons leading to successful assembly and/or
      regeneration of the vertebrate neuromuscular synapse.

PMID- 22612293
TI  - Association of polymorphisms in MCP-1, CCR2, and CCR5 genes with the risk and
      clinicopathological characteristics of prostate cancer.
AB  - The aim of our study was to determine the effect of monocyte chemotactic protein
      1 (MCP-1), CC chemokine receptor 2 (CCR2), and CC chemokine receptor 5 (CCR5)
      gene polymorphisms on the susceptibility and clinicopathological characteristics
      of prostate cancer. Genotyping was performed by polymerase chain reaction (PCR)
      restriction fragment length polymorphism (RFLP) method in 156 histopathologically
      confirmed prostate cancer patients and 152 healthy subjects. Individuals with AA
      genotype or at least one A allele of CCR2 V64I gene polymorphism had a higher
      risk for prostate cancer as compared with those with GG genotype (p=0.010 and
      p=0.028, respectively). CCR5 Delta32/wt genotype and CCR5 Delta32 allele were
      also found to be involved in the susceptibility to prostate cancer (p=0.028 and
      p=0.030, respectively). However, there was no significant association between MCP
      1-2518 A/G gene polymorphism and prostate cancer risk. Prostate cancer patients
      carrying AA genotype or at least one A allele of CCR2 V64I had significantly
      increased risk for high stage disease (p=0.002 and p=0.039, respectively) and
      metastasis (p=0.004 and p=0.022, respectively). The CCR2 A allele (64I allele)
      was significantly associated with high T stage (p=0.001) and metastasis (p=0.005)
      as compared with CCR2 G allele (64V allele). Our data indicate that gene
      polymorphism of CCR2 V64I may influence the susceptibility and
      clinicopathological characteristics of prostate cancer and CCR5 Delta32 allele
      may also be an important risk factor for prostate cancer in Turkish men
      population.

PMID- 22612295
TI  - Efficacy and safety of mixed oriental herbal medicines for treating human
      obesity: a systematic review of randomized clinical trials.
AB  - The objective of this systematic review was to assess the evidence from rigorous
      clinical trials evaluating the efficacy of mixed herbal medicine formulations
      used in traditional Oriental medicines for the treatment of obesity and to
      describe the safety and types of adverse events reported in such trials. To
      accomplish this, 14 databases were searched from inception to July 31, 2009. The
      search terms used were "obesity" or "obese" and "herb," "herbal," or "herbal
      medicine" without language restriction. All randomized clinical trials using
      mixed herbal medicines on obese or overweight subjects were considered for
      inclusion. Of the publications in the identified databases, 1144 results were
      searched and reviewed, and in total 12 studies were included. Their
      methodological quality was assessed using the Jadad score. The results of our
      review provide evidence suggesting that mixed Oriental herbal medicines may be
      safe and effective for the treatment of obesity when compared with conventional
      medicine, placebos, or lifestyle control. Many trials also reported improved
      concomitant conditions including impaired glucose tolerance, hypertension, and
      inflammation. Small numbers of adverse events were reported, but most were mild
      or not related to the intervention in itself. No significant mortality was
      observed in any of the trials. However, the evidence provided by the trials
      reviewed is not fully convincing because of their poor methodological quality.
      Therefore, more research and well-designed clinical trials are necessary to
      address these issues, as well as to assess the safety of mixed Oriental herbal
      medicines used to treat obesity.

PMID- 22612294
TI  - Neuroprotection against oxidative injury by a nucleic acid-based health product
      (Squina DNA) through enhancing mitochondrial antioxidant status and functional
      capacity.
AB  - High levels of reactive oxygen species inflict oxidative damage on various
      cellular components that eventually culminate in a variety of diseases. This
      study investigated the cytoprotective effects of a nucleic acid-based health
      product (Squina [Hong Kong, China] DNA) against oxidative stress, particularly in
      neuronal cells. Adult female Sprague-Dawley rats were treated with Squina DNA,
      and changes in mitochondrial antioxidant status and functional capacity were
      assessed by the activities of antioxidant enzymes and ATP generation capacity in
      brain, heart ventricular, kidney, skeletal muscle, and liver tissues of control
      and Squina DNA-treated rats. The effects of Squina DNA pretreatment on
      brain/neuronal cell injury were investigated in a rat model of cerebral
      ischemia/reperfusion (I/R) injury and a neuroblastoma SH-SY5Y cell model of beta
      amyloid (Abeta) protein fragment 25-35-induced toxicity. Long-term Squina DNA
      treatment caused dose-dependent increases in mitochondrial antioxidant status and
      functional capacity in rat brain, heart ventricular, kidney, skeletal muscle, and
      liver tissues. Squina DNA pretreatment significantly prevented I/R injury in
      brain tissue. The cerebroprotection was associated with a reversal of I/R-induced
      impairment in mitochondrial antioxidant status and disruption in membrane
      integrity. Squina DNA ethanol extract also significantly inhibited the Abeta
      induced apoptosis in SH-SY5Y neuronal cells, as evidenced by less caspase 3 and
      caspase 9 activation as well as mitochondrial cytochrome c release in Abeta
      challenged cells. Squina DNA may enhance the resistance of tissues and cells to
      oxidative stress, particularly in pathological conditions such as stroke and
      aging-related neurodegenerative diseases.

PMID- 22612296
TI  - Velamo do campo: its volatile constituents, secretory elements, and biological
      activity.
AB  - The volatile components from Croton campestris root bark were localized by an
      anatomical study and analyzed by gas chromatography-mass spectrometry for the
      first time. The roots of this plant showed secretory cells. These volatile
      constituents, isolated from the dichloromethane extract by hydrodistillation,
      were analyzed by gas chromatography-mass spectrometry. We found 69 components.
      They were characterized, and the major constituents of crude oil root barks were
      spathulenol (23.3%) and borneol (18.7%). Growth inhibitory activity of the active
      compounds in solution was evaluated by measuring minimal inhibitory
      concentrations using a broth micromethod. The minimal inhibitory concentration of
      root bark volatile constituents was 1.56 MUg/mL for Staphylococcus aureus, 3.125
      MUg/mL for Candida albicans, and 6.25 MUg/mL for Aspergillusniger.

PMID- 22612298
TI  - Iridocorneal angle measurements in mammalian species: normative data by optical
      coherence tomography.
AB  - Objective  Gonioscopy provides limited quantitative information to compare the
      iridocorneal anatomy across different species. In addition, the anatomic
      relationships by histologic examination are altered during processing. As a
      result, the comparative anatomy of the iridocorneal angle across several
      mammalian species was evaluated by Optical Coherence Tomography (OCT). Methods 
      Cats, beagle dogs, minipigs, owl monkeys, cynomolgus monkeys, and rhesus monkeys
      (n = 6 or 7 per species) were evaluated. Imaging was performed using the OCT. The
      anterior chamber angle (ACA), angle opening distance (AOD), and the angle recess
      area (ARA) were evaluated. Results  AC angle: cat (63 +/- 6 degrees ) > owl
      monkey (54 +/- 4 degrees ) > beagle dog (42 +/- 4 degrees ) > minipig (40 +/- 3
      degrees ) > rhesus monkey (36 +/- 1 degrees ) > cynomolgus monkey (34 +/- 2
      degrees ). AOD: cat (3.3 +/- 0.5 mm) > owl monkey (2.05 +/- 0.2 mm) > beagle dog
      (1.08 +/- 0.1 mm) > rhesus monkey (0.92 +/- 0.06 mm) > minipig (0.64 +/- 0.04 mm)
      > cynomolgus monkey (0.43 +/- 0.03 mm). ARA: cat (3.5 +/- 0.1 mm(2) ) > owl
      monkey (1.41 +/- 0.2 mm(2) ) > dog (0.88 +/- 0.1 mm(2) ) > rhesus monkey (0.62 +/
      0.06 mm(2) ) > minipig (0.21 +/- 0.05 mm(2) ) > cynomolgus monkey (0.15 +/- 0.01
      mm(2) ). Conclusions  This study benchmarks the normative iridocorneal angle
      measurements across different mammalian species by OCT. These data can be useful
      to compare iridocorneal angle measurements in disease states as OCT evolves as a
      common diagnostic tool in veterinary ophthalmic research and practice.

PMID- 22612297
TI  - Korean mistletoe (Viscum album coloratum) extract improves endurance capacity in
      mice by stimulating mitochondrial activity.
AB  - The beneficial effects of exercise on overall health make it desirable to
      identify the orally active agents that enhance the effects of exercise in an
      effort to cure metabolic diseases. Natural compounds such as resveratrol (RSV)
      are known to increase endurance by potentiating mitochondrial function. Korean
      mistletoe (Viscum album coloratum) extract (KME) has characteristics similar to
      those of RSV. In the present study, we determined whether KME could increase
      mitochondrial activity and exert an anti-fatigue effect. We found that KME
      treatment significantly increased the mitochondrial oxygen consumption rate (OCR)
      in L6 cells and increased the expression of peroxisome proliferator-activated
      receptor gamma coactivator (PGC)-1alpha and silent mating type information
      regulation 2 homolog 1 (SIRT1), two major regulators of mitochondria function, in
      C2C12 cells. In the treadmill test, KME-treated mice could run 2.5-times longer
      than chow-fed control mice. Additionally, plasma lactate levels of exhausted mice
      were significantly lower in the KME-treated group. In addition, the swimming time
      to exhaustion of mice treated with KME was prolonged by as much as 212% in the
      forced-swim test. Liver and kidney histology was similar between the KME-treated
      and phosphate-buffered saline-treated animals, indicating that KME was nontoxic.
      Taken together, our data show that KME induces mitochondrial activity, possibly
      by activating PGC-1alpha and SIRT1, and improves the endurance of mice, strongly
      suggesting that KME has great potential as a novel mitochondria-activating agent.

PMID- 22612299
TI  - Medication noncompliance and patient satisfaction following percutaneous coronary
      intervention.
AB  - OBJECTIVES: This study evaluated the relationship between medication
      noncompliance and patient satisfaction in patients with drug-eluting stent
      revascularization in Armenia. BACKGROUND: Reasons for medication noncompliance
      are multifactorial--often related to health system, patient, condition, therapy,
      and socioeconomic factors. METHODS: The analytical cross-sectional survey used a
      simple random sample of patients aged 18 and over who had undergone percutaneous
      coronary artery intervention with drug-eluting stent from 2006 to 2008 (n = 271)
      at Nork Marash Medical Center, Yerevan, Armenia. Medication noncompliance was
      assessed using the Morisky Adherence Scale. Patient satisfaction items were
      selected from the Patient Satisfaction Questionnaire (PSQ-18). RESULTS:
      Respondents' mean age was 57.5 +/- 9.8 years. Most (87.8%) were male. Nearly one
      third of patients (31.0%) were noncompliant. Most reported good health (91.9%).
      Respondents most often cited out-of-pocket costs as a reason for noncompliance
      (19.2%). Age, gender, health status, smoking status, and cost were associated
      with medication noncompliance (P < 0.05). Noncompliance was not associated with
      elapsed time after the intervention or satisfaction (P > 0.05). Medication
      noncompliance was positively related to cost (odds ratio [OR]= 2.57, 95% CI =
      1.33-4.97) and inversely related to health status (OR = 0.46, 95% CI = 0.25-0.85)
      and age (OR = 0.94, 95% CI = 0.91-0.97). CONCLUSION: Medication noncompliance is
      a multifactorial problem. Strategies reducing the economic burden on patients
      should improve compliance and, thus, treatment outcomes. These findings further
      efforts to benchmark performance in Armenia and other post-Soviet countries
      against western standards and experiences.

PMID- 22612300
TI  - Exceptional inheritance of plastids via pollen in Nicotiana sylvestris with no
      detectable paternal mitochondrial DNA in the progeny.
AB  - Plastids and mitochondria, the DNA-containing cytoplasmic organelles, are
      maternally inherited in the majority of angiosperm species. Even in plants with
      strict maternal inheritance, exceptional paternal transmission of plastids has
      been observed. Our objective was to detect rare leakage of plastids via pollen in
      Nicotiana sylvestris and to determine if pollen transmission of plastids results
      in co-transmission of paternal mitochondria. As father plants, we used N.
      sylvestris plants with transgenic, selectable plastids and wild-type
      mitochondria. As mother plants, we used N. sylvestris plants with Nicotiana
      undulata cytoplasm, including the CMS-92 mitochondria that cause cytoplasmic male
      sterility (CMS) by homeotic transformation of the stamens. We report here
      exceptional paternal plastid DNA in approximately 0.002% of N. sylvestris
      seedlings. However, we did not detect paternal mitochondrial DNA in any of the
      six plastid-transmission lines, suggesting independent transmission of the
      cytoplasmic organelles via pollen. When we used fertile N. sylvestris as mothers,
      we obtained eight fertile plastid transmission lines, which did not transmit
      their plastids via pollen at higher frequencies than their fathers. We discuss
      the implications for transgene containment and plant evolutionary histories
      inferred from cytoplasmic phylogenies.

PMID- 22612301
TI  - Strategy for stable and high-level expression of recombinant trehalose synthase
      in Escherichia coli.
AB  - Trehalose is a nonreducing disaccharide and has a wide range of applications in
      food and biorelated industry. This sugar can be synthesized from maltose in one
      step by trehalose synthase. In this study, we attempted to overproduce trehalose
      synthase from Picrophilus torridus (PTTS), a thermoacidophilic archaea, in
      Escherichia coli . However, overproduction of PTTS was hampered when the T7
      promoter-driven PTTS gene (PT7-PTTS) on a multicopy plasmid was employed in E.
      coli . The factors limiting PTTS production were identified in a systematic way,
      including the codon bias, plasmid instability, a redundant gene copy, a high
      basal level of PTTS, and metabolic burden resulting from the mutlicopy plasmid
      DNA and antibiotics. To overcome these difficulties, an E. coli strain was
      developed with insertion of PT7-PTTS into the chromosome and enhanced expression
      of genomic argU tRNA and ileX tRNA genes. Without the selective pressure, the
      constructed producer strain was able to produce a stable and high-level
      production of recombinant PTTS. Overall, we proposed a simple and effective
      method to address the issue that is most commonly raised in overproduction of
      heterologous proteins by E. coli . 

PMID- 22612302
TI  - Donor safety in triple plateletpheresis: results from the German and Austrian
      Plateletpheresis Study Group multicenter trial.
AB  - BACKGROUND: The objective was to investigate potential risks for apheresis donors
      associated with a triple-plateletpheresis (TP) program. STUDY DESIGN AND METHODS:
      Eleven hemapheresis centers randomly assigned 411 repeat donors (ratio, 1:1.2) to
      either double plateletpheresis (DP; 185 donors) or TP (226 donors) with a
      platelet (PLT) target content of at least 5.0*10(11) PLTs/DP and at least
      7.5*10(11) PLTs/TP. The primary endpoint was procedure-related postapheresis PLT
      count of at least 150*10(9) /L (probability, >=98%). Secondary endpoints were
      apheresis characteristics and donor adverse reactions. RESULTS: In 6 of 1133 DPs
      (0.5%) in 4 of 185 donors (2.2%) and in 20 of 1020 TPs (2.0%) in 14 of 226 donors
      (6.2%), postapheresis PLT counts were below 150*10(9) /L. There were marginal but
      significant differences in collection efficiency (DP, 69.2+/-9.1%; TP, 70.9+/
      9.0%; p<=0.0001) and collection rate (DP, 10.4*10(9) +/-2.3*10(9) PLTs/min; TP,
      10.8*10(9) +/-2.3*10(9) PLTs/min; p<=0.005). The PLT yields were 5.9*10(11) +/
      0.8*10(11) PLTs for DP and 8.3*10(11) +/-0.9*10(11) PLT for TP (p<=0.0001) at
      processing times of 59+/-13 minutes (DP) versus 80+/-16 minutes (TP; p<=0.0001).
      Significant PLT recruitment (1.10+/-0.14 vs. 1.20+/-0.23; p<0.0001) was seen for
      both DP and TP. DP and TP did not differ with regard to venous access problems
      (VAPs) without discontinuation (3.8% for both), but DP induced fewer VAPs with
      discontinuation (1.1% vs. 3.0%; p<0.01). Mild citrate toxicity (1.7% vs. 3.9%;
      p<0.01) and circulatory reactions (0.4% vs. 2.2%; p<0.01) were more often noticed
      in TP, but caused no increase in discontinuations. CONCLUSIONS: TP results in an
      increase in mild donor reactions but does not significantly impair donor safety
      or product quality.

PMID- 22612304
TI  - Forsterite [Mg2SiO4)] carbonation in wet supercritical CO2: an in situ high
      pressure X-ray diffraction study.
AB  - Mechanisms controlling mineral stabilities in contact with injected supercritical
      fluids containing water are relatively unknown. In this paper, we discuss
      carbonation reactions occurring with forsterite (Mg(2)SiO(4)) exposed to variably
      wet supercritical CO(2) (scCO(2)). Transformation reactions were tracked by in
      situ high-pressure X-ray diffraction in the presence of scCO(2) containing
      dissolved water. Under modest pressures (90 bar) and temperatures (50  degrees
      C), scCO(2) saturated with water converted >70 wt % forsterite to a hydrated
      magnesium carbonate, nesquehonite (MgCO(3) . 3H(2)O), and magnesite (MgCO(3))
      after 72 h. However, comparable tests with scCO(2) at only partial water
      saturation showed a faster carbonation rate but significantly less nesquehonite
      formation and no evidence of the anhydrous form (MgCO(3)). The presence and
      properties of a thin water film, observed by in situ infrared (IR) spectroscopy
      and with isotopically labeled oxygen ((18)O), appears to be critical for this
      silicate mineral to carbonate in low water environments. The carbonation products
      formed demonstrated by temperature and water-content dependence highlights the
      importance of these kinds of studies to enable better predictions of the long
      term fate of geologically stored CO(2).

PMID- 22612303
TI  - Meta-analysis: IL-28B genotype and sustained viral clearance in HCV genotype 1
      patients.
AB  - BACKGROUND: Polymorphisms in the IL-28B region are a strong predictor of
      sustained virologic response (SVR) in individual studies of HCV genotype 1
      patients receiving peginterferon (pegIFN) and ribavirin. AIM: To obtain a pooled
      odds ratio (OR) of SVR in patients of varying race with the favourable IL-28B
      genotype compared to those with the unfavourable genotype. METHODS: A literature
      search was conducted using online databases and a review of conference abstracts.
      A random effects meta-analysis was performed and study heterogeneity and
      publication bias were assessed. RESULTS: There were 21 individual studies of HCV
      genotype 1 patients of varying ethnicity treated with pegIFN and ribavirin. The
      pooled prevalence of the favourable IL-28B genotype varied by race (73% vs. 41%
      vs. 13% in 2612 Asians, 3110 Caucasians and 452 African-Americans, respectively,
      P < 0.001). However, the strength of association of the IL-28B genotype with SVR
      was similar in all three racial groups (Caucasians: odds ratio (OR) 3.88, 2.75
      5.49, African-Americans: OR 4.63, 2.52-8.50 and Asians OR 5.66, 3.99-8.02, all P
      < 0.001). The IL-28B genotype was also associated with SVR in 263 HIV/HCV co
      infected Caucasians (OR 5.49, 3.02-9.96, P < 0.001). Study quality score and anti
      viral treatment regimen did not impact the strength of the association in patient
      subgroups nor in the pooled population. CONCLUSIONS: IL-28B genotype is
      significantly associated with SVR in HCV genotype 1 patients of varying race, as
      well as in HIV co-infected patients, receiving pegIFN and ribavirin. IL-28B
      testing in conjunction with other pre-treatment parameters may prove useful in
      counselling HCV patients.

PMID- 22612305
TI  - Gemcitabine-associated livedoid thrombotic microangiopathy with associated
      sclerema neonatorum-like microscopic changes.
AB  - Gemcitabine is a deoxycytidine analog antimetabolite that is now accepted as
      first-line treatment for advanced and metastatic pancreatic carcinoma.
      Gemcitabine-related thrombotic microangiopathy associated with systemic hemolytic
      uremic syndrome or thrombotic thrombocytopenia purpura has rarely been described.
      Herein, we report a patient who developed a livedoid thrombotic microangiopathy
      with no signs of associated hemolytic-uremic syndrome. Cutaneous thrombotic
      microangiopathy occurred after the administration of his 17th cycle and a
      cumulative dose of 53.65 g/m(2) of gemcitabine. Some authors have suggested that
      this toxicity may be dose-related, and a 10th cycle or a cumulative dose of 9-56
      g/m(2) have been proposed as the prothrombotic threshold. Interestingly,
      dermatopathologic findings were limited to the subcutis and they consisted of
      small-vessel occlusion by intravascular fibrin and leukocytes, vessel wall
      thickening and endothelial cell swelling. Surprisingly, we observed some
      structures arranged radially with needle-shaped clefts resembling those of
      sclerema neonatorum. Awareness of this potential cutaneous toxicity by
      dermatologists and dermatopathologists is extremely important.

PMID- 22612306
TI  - A randomized clinical trial of naltrexone and behavioral therapy for problem
      drinking men who have sex with men.
AB  - OBJECTIVE: This study tested the comparative effectiveness of modified behavioral
      self-control therapy (MBSCT) and naltrexone (NTX), as well as the added benefit
      of combining the 2, in problem drinking men who have sex with men (MSM) seeking
      to reduce but not quit drinking. METHOD: Participants (N = 200) were recruited
      and urn randomized to 1 of 2 medication conditions, NTX or placebo (PBO), and
      either MSBCT or no behavioral intervention, yielding 4 conditions: PBO, NTX,
      MSBCT, and NTX + MSBCT. In addition, all participants received a brief medication
      compliance intervention. Participants were treated for 12 weeks and assessed 1
      week after treatment completion. Two primary outcomes-sum of standard drinks and
      number of heavy drinking days-and 1 secondary outcome-percentage of those
      drinking in a nonhazardous manner (NoH)-were selected a priori. RESULTS: There
      was a significant main effect for MBSCT (all ps < .01) but not NTX on all 3
      outcomes. In addition, the combination of NTX and MBSCT was not more effective
      than either MSCBT or PBO. There was a significant interaction effect on NoH, such
      that NTX significantly increased the likelihood (odds ratio = 3.3) of achieving a
      nonhazardous drinking outcome relative to PBO. In addition, NTX was significantly
      more effective than PBO on a descriptive outcome: negative consequences of
      drinking. CONCLUSIONS: There was no advantage to adding NTX to MBSCT. In
      addition, MBSCT showed stronger evidence of efficacy than NTX. At the same time,
      NTX delivered in the context of a minimal medication compliance intervention was
      significantly more effective than PBO on an important clinical indicator. Results
      provide new information to guide the treatment of problem drinking, including in
      primary care settings.

PMID- 22612307
TI  - The click triazolium peptoid side chain: a strong cis-amide inducer enabling
      chemical diversity.
AB  - Access to homogeneous and discrete folded peptoid structures primarily depends on
      control of the cis/trans isomerism of backbone tertiary amides. This can be
      achieved by designing specific side chains capable of forming local interactions
      with the backbone. This is often undertaken at the expense of side-chain
      diversity, which is a key advantage of peptoids over other families of
      peptidomimetics. We report for the first time a positively charged triazolium
      type side chain that does not compromise diversity and exhibits the best ability
      reported to date for inducing the cis conformation. The cis-directing effect was
      studied in N-acetamide dipeptoid model systems and evaluated in terms of
      K(cis/trans) using NMR spectroscopy in aprotic and protic solvents. Computational
      geometry optimization and natural bond orbital analysis in combination with NOESY
      experiments were consistent with a model in which n -> pi*(Ar) electronic
      delocalization [from carbonyl (O(i-1)) to the antibonding orbital (pi*) of the
      triazolium motif on residue i] may be operative. In the computational model (gas
      phase) and experimentally in CDCl(3), H-bonding between the triazolium C-H proton
      and the C(i)?O(i) oxygen was also identified and may act cooperatively with the n
      -> pi*(Ar) delocalization, resulting in the absence of the trans rotamers in
      CDCl(3).

PMID- 22612308
TI  - Deciduosis can cause remarkable leukocytosis and obscure abdominal pain.
AB  - Remarkable leukocytosis with obscure abdominal pain during pregnancy is
      clinically challenging for obstetricians. A 31-year-old pregnant woman developed
      persistently elevated white blood cell (approximately 30 000/uL) and C-reactive
      protein (3.0 mg/dL) with occasional moderate abdominal pain. At 29 gestational
      weeks, she underwent emergency cesarean section due to suspected abruptio
      placentae. Hemoperitoneum was observed with extensive hemorrhagic nodules on the
      peritoneal and omental surfaces. White blood cells rose 87200/uL, and C-reactive
      protein peaked at 44.9mg/dL after surgery. Pathologically, biopsies showed
      deciduosis, and decidual cells on the omental surface showed immunohistochemical
      staining for granulocyte colony-stimulating factor (G-CSF). Serum G-CSF
      concentration was 339 pg/mL at 28 weeks, and that of ascites was 312 000 pg/mL at
      cesarean section. G-CSF-producing deciduosis can induce leukocytosis as well as
      abdominal pain during pregnancy and postpartum.

PMID- 22612309
TI  - Combining multinuclear high-resolution solid-state MAS NMR and computational
      methods for resonance assignment of glutathione tripeptide.
AB  - We present a complete set of experimental approaches for the NMR assignment of
      powdered tripeptide glutathione at natural isotopic abundance, based on J
      coupling and dipolar NMR techniques combined with (1)H CRAMPS decoupling. To
      fully assign the spectra, two-dimensional (2D) high-resolution methods, such as
      (1)H-(13)C INEPT-HSQC/PRESTO heteronuclear correlations (HETCOR), (1)H-(1)H
      double-quantum (DQ), and (1)H-(14)N D-HMQC correlation experiments, have been
      used. To support the interpretation of the experimental data, periodic density
      functional theory calculations together with the GIPAW approach have been used to
      calculate the (1)H and (13)C chemical shifts. It is found that the shifts
      calculated with two popular plane wave codes (CASTEP and Quantum ESPRESSO) are in
      excellent agreement with the experimental results.

PMID- 22612310
TI  - Interplay between viscoelastic and chemical tunings in fatty-acid-based polyester
      adhesives: engineering biomass toward functionalized step-growth polymers and
      soft networks.
AB  - This Article describes the synthesis and characterization of renewable self
      adhesive coatings with tunable viscoelastic properties and equipped with well
      defined amounts of carboxylic acid "sticker" groups with adhesion promoting
      characteristics. Hydroxyl-ended polyesters with various architectures (linear,
      branched) were synthesized by melt polycondensation of dimerized fatty acids and
      fatty diols and then cured with maleic anhydride-modified triglycerides (such as
      maleinized soybean oil) in the presence of the amidine catalyst 1,8
      diazabicyclo[5.4.0]undec-7-ene. The curing reaction of alcoholysis has the dual
      effect of chain extending/cross-linking the base polymers via creation of
      polymeric half-esters linkages while introducing carboxylic acid functions within
      the gel structure. We demonstrated how the adhesion properties can be finely
      tuned from molecular design and formulation of the network precursors and how the
      rheology and functionality of the coatings influence the adhesive bond formation
      and development. These renewable polyester adhesives proved to be suitable
      materials for pressure-sensitive adhesives applications with respect to adhesion
      strength, viscoelasticity, and functionality. In addition, the environmental
      benefits of such materials are briefly discussed.

PMID- 22612311
TI  - Understanding the edge effect in wetting: a thermodynamic approach.
AB  - Edge effect is known to hinder spreading of a sessile drop. However, the
      underlying thermodynamic mechanisms responsible for the edge effect still is not
      well-understood. In this study, a free energy model has been developed to
      investigate the energetic state of drops on a single pillar (from upright frustum
      to inverted frustum geometries). An analysis of drop free energy levels before
      and after crossing the edge allows us to understand the thermodynamic origin of
      the edge effect. In particular, four wetting cases for a drop on a single pillar
      with different edge angles have been determined by understanding the
      characteristics of FE plots. A wetting map describing the four wetting cases is
      given in terms of edge angle and intrinsic contact angle. The results show that
      the free energy barrier observed near the edge plays an important role in
      determining the drop states, i.e., (1) stable or metastable drop states at the
      pillar's edge, and (2) drop collapse by liquid spilling over the edge completely
      or staying at an intermediate sidewall position of the pillar. This thermodynamic
      model presents an energetic framework to describe the functioning of the so
      called "re-entrant" structures. Results show good consistency with the literature
      and expand the current understanding of Gibbs' inequality condition.

PMID- 22612312
TI  - Preliminary study of thyroid and colon cancers-associated antigens and their
      cognate autoantibodies as potential cancer biomarkers.
AB  - BACKGROUND: Autoantibodies, which are produced against tumor-associated antigens,
      are potential tumor markers and attract a growing interest for cancer detection,
      differential diagnostics and prognosis. OBJECTIVE: To evaluate the diagnostic
      significance of 40 antigens identified by immunoscreening of cDNA libraries from
      thyroid and colon cancers by allogenic screening with different tumor types
      patients' sera. METHOD: Plaque-spot serological assay. RESULTS: Increased
      frequency of antibody response in sera of cancer patients compared with that of
      healthy donors was shown toward 14 antigens, 8 of which (CG016, BTN3A3, FKBP4,
      XRCC4, TSGA2, ACTR1A, FXYD3 and CTSH) have revealed exclusively cancer-related
      serological profile. CONCLUSION: Allogenic screening of 40 SEREX-antigens with
      sera from cancer patients and healthy donors allowed us to reveal 14 antigens
      with potential diagnostic significance. These antigens and their cognate
      autoantibodies could be considered as valuable targets for further analysis as
      potential cancer biomarkers.

PMID- 22612313
TI  - Asymmetric crying face in a newborn with isotretinoin embryopathy.
AB  - We report a newborn with asymmetric crying face and other anomalies whose mother
      had taken isotretinoin during the first month of pregnancy. We hypothesize that
      asymmetric crying face is a finding of retinoic acid embryopathy and results from
      the intrauterine effects of retinoic acid on the development of the depressor
      anguli oris muscle or the mandibular branch of the facial nerve. 

PMID- 22612314
TI  - Glycogen accumulation and degradation by the trichomonads Trichomonas vaginalis
      and Trichomonas tenax.
AB  - Several species of trichomonad have been shown to accumulate significant
      quantities of glycogen during growth, suggesting an important role for this
      compound in cell physiology. We provide the first analysis of the changes in
      glycogen content and glycogen phosphorylase activity that occur during in vitro
      growth of two trichomonad species: Trichomonas vaginalis and Trichomonas tenax.
      Both species accumulated glycogen following inoculation into fresh medium and
      utilized this compound during logarithmic growth. Glycogen phosphorylase activity
      also varied during growth in a species-specific manner. The expression of
      phosphorylase genes in T. vaginalis remained constant during growth and thus
      transcriptional control did not explain the observed fluctuations in
      phosphorylase activity. After cloning, expression, and purification, two
      recombinant glycogen phosphorylases from T. vaginalis and one recombinant
      glycogen phosphorylase from T. tenax had robust activity and, in contrast to many
      other eukaryotic glycogen phosphorylases, did not appear to be regulated by
      reversible protein phosphorylation. Furthermore, allosteric regulation, if
      present, was not mediated by compounds known to impact the activity of better
      characterized phosphorylases.

PMID- 22612316
TI  - Novel genetic markers of the carbonic anhydrase II gene associated with egg
      production and reproduction traits in Tsaiya ducks.
AB  - In our previous cDNA microarray study, we found that the carbonic anhydrase II
      (CA2) gene is one of the differentially expressed transcripts in the duck isthmus
      epithelium during egg formation period. The aim of this study was to identify the
      single-nucleotide polymorphisms (SNPs) in the CA2 gene of Tsaiya ducks. The
      relationship of SNP genotype with egg production and reproduction traits was also
      investigated. A total of 317 ducks from two lines, a control line with no
      selection and a selected line, were employed for testing. Three SNPs (C37T, A62G
      and A65G) in the 3'-untranslated region of the CA2 gene were found. SNP-trait
      association analysis showed that SNP C37T and A62G were associated with duck egg
      weight besides fertility. The ducks with the CT and AG genotypes had a 1.46 and
      1.62 g/egg lower egg weight as compared with ducks with the CC and AA genotypes,
      respectively (p < 0.05). But the ducks with CT and AG genotypes had 5.20% and
      4.22% higher fertility than those with CC and AA genotypes, respectively (p <
      0.05). Diplotype constructed on these three SNPs was associated with duck
      fertility, and the diplotype H1H4 was dominant for duck fertility. These findings
      might provide the basis for balanced selection and may be used in marker-assisted
      selection to improve egg weight and fertility simultaneously in the Tsaiya ducks.

PMID- 22612315
TI  - Pseudohalide anions reveal a novel extracellular site for potentiators to
      increase CFTR function.
AB  - BACKGROUND AND PURPOSE: There is great interest in the development of potentiator
      drugs to increase the activity of the cystic fibrosis transmembrane conductance
      regulator (CFTR) in cystic fibrosis. We tested the ability of several anions to
      potentiate CFTR activity by a novel mechanism. EXPERIMENTAL APPROACH: Patch clamp
      recordings were used to investigate the ability of extracellular pseudohalide
      anions (Co(CN)(6) (3-) , Co(NO(2) )(6) (3-) , Fe(CN)(6) (3-) , IrCl(6) (3-) ,
      Fe(CN)(6) (4-) ) to increase the macroscopic conductance of mutant CFTR in intact
      cells via interactions with cytoplasmic blocking anions. Mutagenesis of CFTR was
      used to identify a possible molecular mechanism of action. Transepithelial short
      circuit current recordings from human airway epithelial cells were used to
      determine effects on net anion secretion. KEY RESULTS: Extracellular pseudohalide
      anions were able to increase CFTR conductance in intact cells, as well as
      increase anion secretion in airway epithelial cells. This effect appears to
      reflect the interaction of these substances with a site on the extracellular face
      of the CFTR protein. CONCLUSIONS AND IMPLICATIONS: Our results identify
      pseudohalide anions as increasing CFTR function by a previously undescribed
      molecular mechanism that involves an interaction with an extracellular site on
      the CFTR protein. Future drugs could utilize this mechanism to increase CFTR
      activity in cystic fibrosis, possibly in conjunction with known intracellularly
      active potentiators.

PMID- 22612318
TI  - Rational synthesis of A2B-type meso-triarylsubporphyrins.
AB  - Rational synthesis of A(2)B-type meso-arylsubporphyrins has been accomplished by
      the condensation of triethylamine-tri-N-tripyrromethene-borane with acid
      chlorides. These subporphyrins are useful for evaluations of the intrinsic
      substituent effects and the influences of substitution patterns, A(3)-type versus
      A(2)B-type substitution.

PMID- 22612317
TI  - Derivation of stromal (skeletal and mesenchymal) stem-like cells from human
      embryonic stem cells.
AB  - Derivation of bone forming cells (osteoblasts) from human embryonic stem cells
      (hESCs) is a prerequisite for their use in clinical applications. However, there
      is no standard protocol for differentiating hESCs into osteoblastic cells. The
      aim of this study was to identify the emergence of a human stromal (mesenchymal
      and skeletal) stem cell (hMSC)-like population, known to be osteoblastic cell
      precursors and to test their osteoblastic differentiation capacity in ex vivo
      cultures and in vivo. We cultured hESCs in a feeder-free environment using serum
      replacement and as suspension aggregates (embryoid bodies; hEBs). Over a 20 day
      developmental period, the hEBs demonstrated increasing enrichment for cells
      expressing hMSC markers: CD29, CD44, CD63, CD56, CD71, CD73, CD105, CD106, and
      CD166 as revealed by immunohistochemical staining and flow cytometry
      (fluorescence-activated cell sorting) analysis. Ex vivo differentiation of hEBs
      using bone morphogenic protein 2 (BMP2) combined with standard osteoblast
      induction medium led to weak osteoblastic induction. Conversely, subcutaneous in
      vivo implantation of day 20 hEBs in immune deficient mice, mixed with
      hydroxyapatite/tricalcium phosphate (HA/TCP) as an osteoconductive scaffold,
      revealed bone and cartilage, and fibrous tissue elements after 8 weeks. These
      tissues were of human origin and there was no evidence of differentiation to
      nonmesodermal tissues. hEBs implanted in the absence of HA/TCP formed vacuolated
      tissue containing glandular, fibrous and muscle-like tissue elements. Conversely,
      implantation of undifferentiated hESCs resulted in the formation of a teratoma
      containing a mixture of endodermal, mesodermal, and ectodermal tissues. Our study
      demonstrates that hMSC-like cells can be obtained from hESCs and they can be
      induced to form skeletal tissues in vivo when combined with HA/TCP. These
      findings are relevant for tissue engineering and suggest that differentiated hEBs
      can provide an unlimited source for functional osteogenic cells.

PMID- 22612319
TI  - Association of interleukin-10-1082 promoter polymorphism with gastric cancer:
      appraisal of a recent meta-analysis.

PMID- 22612321
TI  - Clustering of temperamental and cognitive risk factors for anxiety in a college
      sample of late adolescents.
AB  - Temperamental vulnerabilities (e.g., behavioral inhibition, anxiety sensitivity)
      and cognitive biases (e.g., interpretive and judgment biases) may exacerbate
      feelings of stress and anxiety, particularly among late adolescents during the
      early years of college. The goal of the present study was to apply person
      centered analyses to explore possible heterogeneity in the patterns of these four
      risk factors in late adolescence, and to examine associations with several
      anxiety outcomes (i.e., worry, anxiety symptoms, and trait anxiety). Cluster
      analyses in a college sample of 855 late adolescents revealed a Low-Risk group,
      along with four reliable clusters with distinct profiles of risk factors and
      anxiety outcomes (Inhibited, Sensitive, Cognitively-Biased, and Multi-Risk). Of
      the risk profiles, Multi-Risk youth experienced the highest levels of anxiety
      outcomes, whereas Inhibited youth experienced the lowest levels of anxiety
      outcomes. Sensitive and Cognitively-Biased youth experienced comparable levels of
      anxiety-related outcomes, despite different constellations of risk factors.
      Implications for interventions and future research are discussed.

PMID- 22612322
TI  - Subcellular localization and transcription regulatory potency of
      KCNIP/Calsenilin/DREAM/KChIP proteins in cultured primary cortical neurons do not
      provide support for their role in CRE-dependent gene expression.
AB  - KCNIP3/KChIP3 (voltage-dependent K+ channel interacting protein 3), alias
      Calsenilin and downstream regulatory element antagonist modulator (DREAM), is a
      multifunctional protein that modulates A-type potassium channels, affects
      processing of amyloid precursor protein and regulates transcription. KCNIP3 has
      been described to negatively influence the activity of CREB (cAMP/Ca(2+)-response
      element binding protein), an essential factor in neuronal activity-dependent gene
      expression regulation. However, reports on intracellular localization of KCNIP3
      in neurons are diverse and necessitate additional analyses of distribution of
      KCNIPs in cells to clarify the potential of KCNIP3 to fulfill its functions in
      different cell compartments. Here, we examined localization of the entire family
      of highly similar KCNIP proteins in neuronal cells and show that over-expressed
      isoforms of KCNIP1/KChIP1, KCNIP2/KChIP2, KCNIP3/KChIP3, and KCNIP4/KChIP4 had
      varied, yet partially overlapping subcellular localization. In addition, although
      some of the over-expressed KCNIP isoforms localized to the nucleus, endogenous
      KCNIPs were not detected in nuclei of rat primary cortical neurons. Moreover, we
      analyzed the role of KCNIP proteins in cAMP/Ca(2+)-response element (CRE)
      dependent transcription by luciferase reporter assay and electrophoretic mobility
      shift assay and report that our results do not support the role for KCNIPs,
      including DREAM/Calsenilin/KChIP3, in modulation of CREB-mediated transcription
      in neurons.

PMID- 22612323
TI  - Oxidative damage to pre-eclamptic placenta: immunohistochemical expression of
      VEGF, nitrotyrosine residues and von Willebrand factor.
AB  - OBJECTIVE: To determine the relationship of biomarkers of placental damage by
      oxidative stress in pre-eclamptic placenta. METHODS: A case-control study was
      performed on a population of 14 pregnant women with PE and 12 women with normal
      pregnancies. Immunohistochemical expressions of VEGF, vWF distribution, (Na + K)
      ATPase activity, and abundance of nitrotyrosine residues, were assessed in the
      placental tissue. RESULTS: Women with pre-eclampsia showed increased VEGF
      expression and abundance of nitrotyrosine residues in placental villous, and
      plasma vWF levels (p < 0.05), whereas placental (Na + K)-ATPase activity were
      significantly reduced. The syncytiotrophoblast and the maternal space of pre
      eclamptic placenta showed diminished and increased vWF expression, respectively,
      but no significant differences in its expression were found in the placental
      endothelium and stroma (p < 0.05). CONCLUSIONS: It could be suggested that
      increased oxidative stress and VEGF contribute to enhance the impairment of
      placental perfusion by increasing peroxynitrite formation, product of the NO and
      superoxide reaction, thereby partly contributing to account for the
      pathophysiology of this disease. The presence of vWF in the maternal space and
      its diminished expression in syncytiotrophoblast of pre-eclamptic placenta also
      might have pathogenic implications.

PMID- 22612324
TI  - Vitamin D receptor, CYP27B1 and CYP24A1 genes polymorphisms association with oral
      cancer risk and survival.
AB  - BACKGROUND: Genetic polymorphisms of vitamin D receptor gene (VDR) and genes
      involved in vitamin D metabolism pathway, CYP27B1 and CYP24B1, may affect
      individual susceptibility to oral squamous cell carcinoma. The purpose of this
      study was to evaluate the associations between VDR, CYP27B1 and CYP24A1 gene
      polymorphisms with oral cancer risk and survival. METHODS: Study cohort consisted
      of 110 patients with oral cancer and 122 healthy controls. The genotypes of the
      analysed genes were determined by PCR-RFLP or real-time PCR method. RESULTS: The
      significant decrease of oral cancer risk was observed in individuals with
      heterozygote genotype of CYP24A1 gene (rs2296241) (odds ratio 0.281, P = 0.000)
      in comparison with wild type. Patients with VDR FokI ff wild type genotype had
      significantly worse overall survival (P = 0.012, log rank) compared with
      heterozygous and mutated genotype combined. A stratified analysis by the lymph
      node involvement and tumour stage showed that ff is associated with poor survival
      in groups with and without lymph node involvement (P = 0.025, P = 0.040,
      respectively) and in stage III tumours (P = 0.026). Multivariate Cox's regression
      analysis revealed that VDR FokI could be considered an independent prognostic
      factor. CONCLUSION: Our findings indicate that CYP24A1 gene polymorphism might
      have an influence on the susceptibility to oral cancer. VDR FokI polymorphism was
      associated with worse survival and could be considered as an independent
      prognostic marker.

PMID- 22612325
TI  - Music and epilepsy: a critical review.
AB  - The effect of music on patients with epileptic seizures is complex and at present
      poorly understood. Clinical studies suggest that the processing of music within
      the human brain involves numerous cortical areas, extending beyond Heschl's gyrus
      and working within connected networks. These networks could be recruited during a
      seizure manifesting as musical phenomena. Similarly, if certain areas within the
      network are hyperexcitable, then there is a potential that particular sounds or
      certain music could act as epileptogenic triggers. This occurs in the case of
      musicogenic epilepsy, whereby seizures are triggered by music. Although it
      appears that this condition is rare, the exact prevalence is unknown, as often
      patients do not implicate music as an epileptogenic trigger and routine
      electroencephalography does not use sound in seizure provocation. Music therapy
      for refractory epilepsy remains controversial, and further research is needed to
      explore the potential anticonvulsant role of music. Dopaminergic system
      modulation and the ambivalent action of cognitive and sensory input in
      ictogenesis may provide possible theories for the dichotomous proconvulsant and
      anticonvulsant role of music in epilepsy. The effect of antiepileptic drugs and
      surgery on musicality should not be underestimated. Altered pitch perception in
      relation to carbamazepine is rare, but health care professionals should discuss
      this risk or consider alternative medication particularly if the patient is a
      professional musician or native-born Japanese. Studies observing the effect of
      epilepsy surgery on musicality suggest a risk with right temporal lobectomy,
      although the extent of this risk and correlation to size and area of resection
      need further delineation. This potential risk may bring into question whether
      tests on musical perception and memory should form part of the preoperative
      neuropsychological workup for patients embarking on surgery, particularly that of
      the right temporal lobe.

PMID- 22612326
TI  - Endoscopic dilation is an efficacious and safe treatment of intestinal strictures
      in Crohn's disease.
AB  - BACKGROUND: Bowel strictures are a major cause of morbidity, hospitalisation and
      surgery in Crohn's disease. AIM: We report short- and long-term efficacy and
      safety of endoscopic balloon dilation of strictures due to Crohn's disease.
      METHODS: Retrospective study of patients who underwent endoscopic balloon
      dilation between 1987 and 2009. RESULTS: We performed 776 dilations, of which 621
      (80%) were on anastomotic strictures, in 178 patients (94 women) with Crohn's
      disease. At first dilation, median (IQR) age of patients was 45 (37-56) years and
      disease duration 16 (8-22) years. Technical success rate was 689/776 (89%). A
      subset of 75 patients from the primary catchment area, with >5-year follow-up,
      underwent a total of 246 dilations. At 1-year follow-up, 60/75 (80%) patients had
      undergone no further intervention or one additional dilation only. At 3 and 5
      years, corresponding figures were 43/75 (57%) and 39/75 (52%). Cumulative
      proportions of patients undergoing surgery at 1, 3 and 5 years were 13%, 28% and
      36%. Complication rate per procedure for all 178 patients was 41/776 (5.3%),
      bowel perforation (n = 11, 1.4%), major bleeding requiring blood transfusion (n =
      8, 1.0%), minor bleeding (n = 10, 1.3%) and abdominal pain or fever (n = 12,
      1.5%). Ten patients underwent surgery due to complications (perforation n = 8,
      bleeding n = 2). There was no procedure-related mortality. CONCLUSIONS:
      Endoscopic balloon dilation is an efficacious and safe alternative to surgical
      resection of intestinal strictures in Crohn's disease. At 5-year follow-up, 52%
      of patients required no further or one additional dilation only, whereas 36% had
      undergone surgical resection. Complication frequency was low.

PMID- 22612327
TI  - Treatment of whole blood with riboflavin plus ultraviolet light, an alternative
      to gamma irradiation in the prevention of transfusion-associated graft-versus
      host disease?
AB  - BACKGROUND: Exposure of blood products to gamma irradiation is currently the
      standard of care in the prevention of transfusion-associated graft-versus-host
      disease (TA-GVHD). Regulatory, technical, and clinical challenges associated with
      the use of gamma irradiators are driving efforts to develop alternatives.
      Pathogen reduction methods were initially developed to reduce the risk of
      microbial transmission by blood components. Through modifications of nucleic
      acids, these technologies interfere with the replication of both pathogens and
      white blood cells (WBCs). To date, systems for pathogen and WBC inactivation of
      products containing red blood cells are less well established than those for
      platelets and plasma. STUDY DESIGN AND METHODS: In this study, the in vitro and
      in vivo function of WBCs present in whole blood after exposure to riboflavin plus
      ultraviolet light (Rb-UV) was examined and compared to responses of WBCs obtained
      from untreated or gamma-irradiated blood by measuring proliferation, cytokine
      production, activation, and antigen presentation and xenogeneic (X-)GVHD
      responses in an in vivo mouse model. RESULTS: In vitro studies demonstrated that
      treatment of whole blood with Rb-UV was as effective as gamma irradiation in
      preventing WBC proliferation, but was more effective in preventing antigen
      presentation, cytokine production, and T-cell activation. Consistent with in
      vitro findings, treatment with Rb-UV was as effective as gamma irradiation in
      preventing X-GVHD, a mouse model for TA-GVHD. CONCLUSION: The ability to
      effectively inactivate WBCs in fresh whole blood using Rb-UV, prior to separation
      into components, provides the transfusion medicine community with a potential
      alternative to gamma irradiation.

PMID- 22612328
TI  - Moderators of the feature-positive effect in abstract hypothesis-evaluation
      tasks.
AB  - Three studies using abstract materials tested possible moderators of the feature
      positive effect in hypothesis evaluation whereby people use the presence of
      features more than their absence to judge which of 2 competing hypotheses is more
      likely. Drawing on a distinction made in visual perception research, we tested
      whether the feature-positive effect emerges both when using nonsubstitutive
      features, which can be removed without replacement by other features, and
      substitutive features, the absence of which implies the presence of other
      features (e.g., the colour red, the absence of which entails the presence of
      another colour). Furthermore, we tested whether presenting to participants both
      the clue occurrence probabilities (which are needed to consider clue presence)
      and their complements (which are needed to gauge the impact of the absent clues)
      decreased the feature-positive effect. The results showed that regardless of the
      type of feature (i.e., nonsubstitutive vs. substitutive), participants provided
      more responses consistent with an evaluation of the subset of present clues
      compared to all other kinds of responses. However, the use of substitutive
      features combined with an explicit presentation format of probabilistic
      information had a debiasing effect. Furthermore, the use of substitutive features
      negated participant sensitivity to the rarity of clues, whereby the feature
      positive effect decreased when there was one absent clue and two present clues
      for problems in which the exclusive consideration of the presence of features did
      not suggest the correct response.

PMID- 22612329
TI  - Direct binding assay for the detection of type IV allosteric inhibitors of Abl.
AB  - Abelson (Abl) tyrosine kinase is an important cellular enzyme that is rendered
      constitutively active in the breakpoint cluster region (BCR)-Abl fusion protein,
      contributing to several forms of leukemia. Although inhibiting BCR-Abl activity
      with imatinib shows great clinical success, many patients acquire secondary
      mutations that result in resistance to imatinib. Second-generation inhibitors
      such as dasatinib and nilotinib can overcome the majority of these mutations but
      fail to treat patients with an especially prevalent T315I mutation at the
      gatekeeper position of the kinase domain. However, a combination of nilotinib
      with an allosteric type IV inhibitor was recently shown to overcome this
      clinically relevant point mutation. In this study, we present the development of
      a direct binding assay that enables the straightforward detection of allosteric
      inhibitors which bind within the myristate pocket of Abl. The assay is amenable
      to high-throughput screening and exclusively detects the binding of ligands to
      this unique allosteric site.

PMID- 22612330
TI  - Oriented surface immobilization of antibodies at the conserved nucleotide binding
      site for enhanced antigen detection.
AB  - The conserved nucleotide binding site (NBS), found on the Fab variable domain of
      all antibody isotypes, remains a not-so-widely known and unutilized site. Here,
      we describe a UV photo-cross-linking method (UV-NBS) that utilizes the NBS for
      oriented immobilization of antibodies onto surfaces, such that the antigen
      binding activity remains unaffected. Indole-3-butyric acid (IBA) has an affinity
      for the NBS with a K(d) ranging from 1 to 8 MUM for different antibody isotypes
      and can be covalently photo-cross-linked to the antibody at the NBS upon exposure
      to UV light. Using the UV-NBS method, antibody was successfully immobilized on
      synthetic surfaces displaying IBA via UV photo-cross-linking at the NBS. An
      optimal UV exposure of 2 J/cm(2) yielded significant antibody immobilization on
      the surface with maximal relative antibody activity per immobilized antibody
      without any detectable damage to antigen binding activity. Comparison of the UV
      NBS method with two other commonly used methods, epsilon-NH(3)(+) conjugation and
      physical adsorption, demonstrated that the UV-NBS method yields surfaces with
      significantly enhanced antigen detection efficiency, higher relative antibody
      activity, and improved antigen detection sensitivity. Taken together, the UV-NBS
      method provides a practical, site-specific surface immobilization method, with
      significant implications in the development of a large array of platforms with
      diverse sensor and diagnostic applications.

PMID- 22612331
TI  - Development of polarizable models for molecular mechanical calculations. 4. van
      der Waals parametrization.
AB  - In the previous publications of this series, we presented a set of Thole induced
      dipole interaction models using four types of screening functions. In this work,
      we document our effort to refine the van der Waals parameters for the Thole
      polarizable models. Following the philosophy of AMBER force field development,
      the van der Waals (vdW) parameters were tuned for the Thole model with linear
      screening function to reproduce both the ab initio interaction energies and the
      experimental densities of pure liquids. An in-house genetic algorithm was applied
      to maximize the fitness of "chromosomes" which is a function of the root-mean
      square errors (RMSE) of interaction energy and liquid density. To efficiently
      explore the vdW parameter space, a novel approach was developed to estimate the
      liquid densities for a given vdW parameter set using the mean residue-residue
      interaction energies through interpolation/extrapolation. This approach allowed
      the costly molecular dynamics simulations be performed at the end of each
      optimization cycle only and eliminated the simulations during the cycle. Test
      results show notable improvements over the original AMBER FF99 vdW parameter set,
      as indicated by the reduction in errors of the calculated pure liquid densities
      (d), heats of vaporization (H(vap)), and hydration energies. The average percent
      error (APE) of the densities of 59 pure liquids was reduced from 5.33 to 2.97%;
      the RMSE of H(vap) was reduced from 1.98 to 1.38 kcal/mol; the RMSE of solvation
      free energies of 15 compounds was reduced from 1.56 to 1.38 kcal/mol. For the
      interaction energies of 1639 dimers, the overall performance of the optimized vdW
      set is slightly better than the original FF99 vdW set (RMSE of 1.56 versus 1.63
      kcal/mol). The optimized vdW parameter set was also evaluated for the exponential
      screening function used in the Amoeba force field to assess its applicability for
      different types of screening functions. Encouragingly, comparable performance was
      observed when the optimized vdW set was combined with the Thole Amoeba-like
      polarizable model, particularly for the interaction energy and liquid density
      calculations. Thus, the optimized vdW set is applicable to both types of Thole
      models with either linear or Amoeba-like screening functions.

PMID- 22612333
TI  - Low proliferative potential and impaired angiogenesis of cultured rat kidney
      endothelial cells.
AB  - OBJECTIVE: CKD is histologically characterized by interstitial fibrosis, which
      may be driven by peritubular capillary dropout and hypoxia. Surprisingly,
      peritubular capillaries have little repair capacity. We sought to establish long
      term cultures of rat kidney endothelial cells to investigate their growth
      regulatory properties. METHODS: AKEC or YKEC were isolated using CD31-based
      isolation techniques and sustained in long-term cultures. RESULTS: Although YKEC
      grew slightly better than AKEC, both performed poorly compared with endothelial
      cells of the rat adult PMVEC, PAEC, or HUVEC cells. PMVEC and PAEC contained a
      large percentage of cells with high colony-forming potential. In contrast, KECs
      were incapable of forming large colonies and most remained as single nondividing
      cells. KEC expressed high levels of mRNA for VEGF receptors, but were
      surprisingly insensitive to VEGF stimulation. KEC did not form branching
      structures on Matrigel when cultured alone, but in mixed cultures, KEC
      incorporated into branching structures with PMVEC. CONCLUSIONS: These data
      suggest that the intrinsic growth of rat kidney endothelial cells is limited by
      unknown mechanisms. The low growth rate may be related to the minimal intrinsic
      regenerative capacity of renal capillaries.

PMID- 22612334
TI  - Characterization of crude glycerol from biodiesel plants.
AB  - Characterization of crude glycerol is very important to its value-added
      conversion. In this study, the physical and chemical properties of five biodiesel
      derived crude glycerol samples were determined. Three methods, including
      iodometric-periodic acid method, high performance liquid chromatography (HPLC),
      and gas chromatography (GC), were shown to be suitable for the determination of
      glycerol content in crude glycerol. The compositional analysis of crude glycerol
      was successfully achieved by crude glycerol fractionation and characterization of
      the obtained fractions (aqueous and organic) using titrimetric, HPLC, and GC
      analyses. The aqueous fraction consisted mainly of glycerol, methanol, and water,
      while the organic fraction contained fatty acid methyl esters (FAMEs), free fatty
      acids (FFAs), and glycerides. Despite the wide variations in the proportion of
      their components, all raw crude glycerol samples were shown to contain glycerol,
      soap, methanol, FAMEs, water, glycerides, FFAs, and ash. 

PMID- 22612332
TI  - Targeting cannabinoid receptor CB(2)  in cardiovascular disorders: promises and
      controversies.
AB  - Cardiovascular disease is the leading cause of death and disability worldwide,
      which can be largely attributed to atherosclerosis, a chronic inflammation of the
      arteries characterized by lesions containing immune and smooth muscle cells,
      lipids and extracellular matrix. In recent years, the lipid endocannabinoid
      system has emerged as a new therapeutic target in variety of disorders associated
      with inflammation and tissue injury, including those of the cardiovascular
      system. The discovery that Delta-9-tetrahydrocannabinol (Delta9-THC), the main
      active constituent of marijuana, inhibited atherosclerotic plaque progression via
      a cannabinoid 2 (CB(2) ) receptor-dependent anti-inflammatory mechanism, and that
      certain natural and synthetic cannabinoid ligands could modulate the myocardial
      or cerebral ischaemia-reperfusion-induced tissue damage, have stimulated impetus
      for a growing number of studies investigating the implication of CB(2)  receptors
      in atherosclerosis, restenosis, stroke, myocardial infarction and heart failure.
      The aim of this review is to update on recent findings and controversies on the
      role of CB(2)  receptors in cardiovascular disease. Particular emphasis will be
      placed on novel insights in the potential cellular targets of CB(2)  stimulation
      in cardiovascular system (e.g. endothelial and vascular smooth muscle cells,
      cardiomyocytes, infiltrating and/or resident monocytes/macrophages and
      leukocytes, etc.), their interplay and intracellular signalling mechanisms
      identified, as well as on experimental and clinical studies.

PMID- 22612335
TI  - PHO1 expression in guard cells mediates the stomatal response to abscisic acid in
      Arabidopsis.
AB  - Stomatal opening and closing are driven by ion fluxes that cause changes in guard
      cell turgor and volume. This process is, in turn, regulated by environmental and
      hormonal signals, including light and the phytohormone abscisic acid (ABA). Here,
      we present genetic evidence that expression of PHO1 in guard cells of Arabidopsis
      thaliana is required for full stomatal responses to ABA. PHO1 is involved in the
      export of phosphate into the root xylem vessels and, as a result, the pho1 mutant
      is characterized by low shoot phosphate levels. In leaves, PHO1 was found
      expressed in guard cells and up-regulated following treatment with ABA. The pho1
      mutant was unaffected in production of reactive oxygen species following ABA
      treatment, and in stomatal movements in response to light cues, high
      extracellular calcium, auxin, and fusicoccin. However, stomatal movements in
      response to ABA treatment were severely impaired, both in terms of induction of
      closure and inhibition of opening. Micro-grafting a pho1 shoot scion onto wild
      type rootstock resulted in plants with normal shoot growth and phosphate content,
      but failed to restore normal stomatal response to ABA treatment. PHO1 knockdown
      using RNA interference specifically in guard cells of wild-type plants caused a
      reduced stomatal response to ABA. In agreement, specific expression of PHO1 in
      guard cells of pho1 plants complemented the mutant guard cell phenotype and re
      established ABA sensitivity, although full functional complementation was
      dependent on shoot phosphate sufficiency. Together, these data reveal an
      important role for phosphate and the action of PHO1 in the stomatal response to
      ABA.

PMID- 22612336
TI  - A modified surgical approach to the Al-Ghorab shunt - an anatomical basis.

PMID- 22612337
TI  - Critical assessment of the European Association of Urology guideline indications
      for pelvic lymph node dissection at radical prostatectomy.

PMID- 22612339
TI  - Mesh social networking: a patient-driven process.

PMID- 22612343
TI  - Sensitive electrochemiluminescence detection of c-Myc mRNA in breast cancer cells
      on a wireless bipolar electrode.
AB  - We report an ultrasensitive wireless electrochemiluminescence (ECL) protocol for
      the detection of a nucleic acid target in tumor cells on an indium tin oxide
      bipolar electrode (BPE) in a poly(dimethylsiloxane) microchannel. The approach is
      based on the modification of the anodic pole of the BPE with antisense DNA as the
      recognition element, Ru(bpy)(3)(2+)-conjugated silica nanoparticles
      (RuSi@Ru(bpy)(3)(2+)) as the signal amplification tag, and reporter DNA as a
      reference standard. It employs the hybridization-induced changes of
      RuSi@Ru(bpy)(3)(2+) ECL efficiency for the specific detection of reporter DNA
      released from tumor cells. Prior to ECL detection, tumor cells are transfected
      with CdSe@ZnS quantum dot (QD)-antisense DNA/reporter DNA conjugates. Upon the
      selective binding of antisense DNA probes to intracellular target mRNA, reporter
      DNA will be released from the QDs, which indicates the amount of the target mRNA.
      The proof of concept is demonstrated using a proto-oncogene c-Myc mRNA in MCF-7
      cells (breast cancer cell line) as a model target. The wireless ECL biosensor
      exhibited excellent ECL signals which showed a good linear range over 2 * 10(-16)
      to 1 * 10(-11) M toward the reporter DNA detection and could accurately quantify
      c-Myc mRNA copy numbers in living cells. C-Myc mRNA in each MCF-7 cell and LO2
      cell was estimated to be 2203 and 13 copies, respectively. This wireless ECL
      strategy provides great promise in a miniaturized device and may facilitate the
      achievement of point of care testing.

PMID- 22612344
TI  - Saliva proteome research: current status and future outlook.
AB  - Human saliva harbours proteins of clinical relevance and about 30% of blood
      proteins are also present in saliva. This highlights that saliva can be used for
      clinical applications just as urine or blood. However, the translation of
      salivary biomarker discoveries into clinical settings is hampered by the dynamics
      and complexity of the salivary proteome. This review focuses on the current
      status of technological developments and achievements relating to approaches for
      unravelling the human salivary proteome. We discuss the dynamics of the salivary
      proteome, as well as the importance of sample preparation and processing
      techniques and their influence on downstream protein applications; post
      translational modifications of salivary proteome and protein: protein
      interactions. In addition, we describe possible enrichment strategies for
      discerning post-translational modifications of salivary proteins, the potential
      utility of selected-reaction-monitoring techniques for biomarker discovery and
      validation, limitations to proteomics and the biomarker challenge and future
      perspectives. In summary, we provide recommendations for practical saliva
      sampling, processing and storage conditions to increase the quality of future
      studies in an emerging field of saliva clinical proteomics. We propose that the
      advent of technologies allowing sensitive and high throughput proteome-wide
      analyses, coupled to well-controlled study design, will allow saliva to enter
      clinical practice as an alternative to blood-based methods due to its simplistic
      nature of sampling, non-invasiveness, easy of collection and multiple collections
      by untrained professionals and cost-effective advantages. 

PMID- 22612345
TI  - Maternal hypoxia and caffeine exposure depress fetal cardiovascular function
      during primary organogenesis.
AB  - AIMS: Hypoxia is known to influence cardiovascular (CV) function, in part,
      through adenosine receptor activation. We have shown in a mouse model that during
      primary cardiac morphogenesis, acute maternal hypoxia negatively affects fetal
      heart rate, and recurrent maternal caffeine exposure reduces fetal cardiac output
      (CO) and downregulates fetal adenosine A(2A) receptor gene expression. In the
      present study, we investigated whether maternal caffeine dosing exacerbates the
      fetal CV response to acute maternal hypoxia during the primary morphogenesis
      period. MATERIAL AND METHODS: Gestational-day-11.5 pregnant mice were exposed to
      hypoxia (45 s duration followed by 10 min of recovery and repeated 3 times) while
      simultaneously monitoring maternal and fetal CO using high-resolution
      echocardiography. RESULTS:   Following maternal hypoxia exposure, maternal CO
      transiently decreased and then returned to pre-hypoxia baseline values. In
      contrast to a uniform maternal cardiac response to each exposure to hypoxia, the
      fetal CO recovery time to the baseline decreased, and CO rebounded above baseline
      following the second and third episodes of maternal hypoxia. Maternal caffeine
      treatment inhibited the fetal CO recovery to maternal hypoxia by lengthening the
      time to CO recovery and eliminating the CO rebound post-recovery. Selective
      treatment with an adenosine A(2A) receptor antagonist, but not an adenosine A(1)
      receptor antagonist, reproduced the altered fetal CO response to maternal hypoxia
      created by caffeine exposure. CONCLUSIONS:   Results suggest an additive negative
      effect of maternal caffeine on the fetal CV response to acute maternal hypoxia,
      potentially mediated via adenosine A(2A) receptor inhibition during primary
      cardiovascular morphogenesis.

PMID- 22612346
TI  - Superficial epidermolytic ichthyosis: a report of two families.
AB  - Superficial epidermolytic ichthyosis (SEI), previously known as ichthyosis
      bullosa of Siemens, is a rare genetic skin condition, characterized by blisters
      and hyperkeratosis. It can be easily confused with epidermolytic hyperkeratosis,
      known now as epidermolytic ichthyosis, and genetic testing can be helpful in
      differentiating between the two conditions. We describe two children with SEI
      confirmed by genetic testing, including one with a novel mutation. We also
      describe other affected family members with SEI. 

PMID- 22612347
TI  - Detection of neurotrophin-4 (NT-4) in ejaculated bull spermatozoa and its effect
      on spermatozoa mitochondrial activity.
AB  - Recently, we demonstrated that two members of neurotrophins, nerve growth factor
      and brain-derived neurotrophic factor, and two types of receptor, tyrosine kinase
      A (TrkA) and tyrosine kinase (TrkB), exist in ejaculated bull spermatozoa, and
      play a crucial role in the normal function of spermatozoa. Neurotrophin-4 (NT-4)
      is another neurotrophic factor that signals predominantly through the TrkB
      receptor tyrosine kinase, and no reports of detection of NT-4 in spermatozoa have
      been published. In the present study, the presence of NT-4 in mature bull
      spermatozoa was investigated using RT-PCR, immunofluorescence and Western
      blotting. The result shows that there was no RT-PCR evidence for NT-4 transcripts
      in bovine spermatozoa. However, the NT-4 protein was present in bovine
      spermatozoa, and the NT-4 immunoreactivity was localized to the equatorial
      segment and midpiece of bovine spermatozoa. In addition, effects of NT-4 on
      function of spermatozoa were studied. Significant increased mitochondria activity
      of mature bovine spermatozoa was observed in response to 300 or 500 ng/ml
      exogenous NT-4 (p < 0.05), in comparison with the control, while addition of
      inhibitors (40 ng/ml k252alpha) specific for tyrosine protein kinase
      significantly blocked the increase of mitochondria activity. However, NT-4 had no
      effects on the viability or acrosome reaction of spermatozoa (p > 0.05).
      Consequently, this study provided evidence that NT-4 protein was presented in the
      mature bull spermatozoa and can influence the mitochondrial activity of bovine
      spermatozoa through TrkB tyrosine kinase-dependent pathways.

PMID- 22612348
TI  - Manual microdissection technique in a case of subcutaneous panniculitis-like T
      cell lymphoma: a case report and review.
AB  - Demonstration of T-cell receptor gene monoclonality often plays an important role
      in the diagnosis of T-cell lymphoma. When a test to detect monoclonality is
      performed on whole tissue sections, the presence of a reactive lymphocyte
      population may reduce sensitivity. This may be especially true for early or
      borderline cases of lymphoma. Microdissection techniques may be utilized to more
      readily identify a clonal population of lymphocytes. Subcutaneous panniculitis
      like T-cell lymphoma represents a cutaneous lymphoid neoplasm whose clinical
      course may vary from an indolent, waxing and waning course to an aggressive
      course resulting in death. We report the first case of a microdissection
      technique used to facilitate diagnosing a case of subcutaneous panniculitis-like
      T-cell lympoma.

PMID- 22612349
TI  - Total synthesis of (-)-galanthamine and (-)-lycoramine via catalytic asymmetric
      hydrogenation and intramolecular reductive Heck cyclization.
AB  - A synthetic strategy featuring efficient ruthenium-catalyzed asymmetric
      hydrogenation of racemic alpha-aryloxy cyclic ketone via dynamic kinetic
      resolution and palladium-catalyzed intramolecular reductive Heck cyclization has
      been developed for the asymmetric total synthesis of (-)-galanthamine (20.1%, 12
      steps) and (-)-lycoramine (40.2%, 10 steps).

PMID- 22612350
TI  - Preface for the proceedings of the 13th Biannual Meeting of the Child Vision
      Research Society, June 2011 at Royal Visio, Huizen, the Netherlands.

PMID- 22612351
TI  - Effects of magnifier training: evidence from a camera built in the magnifier.
AB  - PURPOSE: This study evaluated the effect of an evidence-based magnifier training
      on viewing behavior in visually impaired children aged 3 to 61/2 years. METHODS:
      Effects of a training with a stand magnifier were evaluated by analyzing
      recordings of 21 visually impaired children, obtained from a miniature camera
      mounted in the magnifier. In a pre-test, post-test design, 11 of the children
      trained without magnifier and 10 children trained with magnifier. Three measures
      were compared from pre- to post-test assessment: 1) observation time in seconds
      through the magnifier during task performance; 2) the eye that was used during
      task performance with the magnifier (right eye/left eye as recorded by the
      camera); and 3) the self-chosen eye-to-chart distance (in cm) in near visual
      acuity measurement. RESULTS: Three important changes were found by analyzing the
      eye-camera recordings: (1) There was a significant shift in average observation
      time (i.e., the duration of looking through the magnifier in a single glance),
      before and after training. In the pre-test children used less than 10 s for a
      glance through the magnifier, whereas in the post-test this was 10-30 s. (2) In 5
      children there was no preference with respect to the number of glances through
      the magnifier with right or left eye during pre-test measurement. However, such a
      task-specific dominance was clearly observed in this subgroup after training
      (post-test measurement). (3) The eye-to-chart distance, as measured during near
      vision testing with LH-single and LH-line test, decreased significantly over the
      training period (from 9.5 cm to 7.9 cm, pre- to post-test). There were no
      differences in the outcome measures between the with-magnifier and without
      magnifier training groups. We can conclude that (1) the magnifier training had a
      positive effect on viewing behavior and the development of dominance, and (2)
      camera observations provide valuable data on children's viewing behavior.

PMID- 22612352
TI  - Crowding ratio in young normally sighted children.
AB  - PURPOSE: To determine normal values of the crowding ratio (CR) in children.
      METHODS: Of 62 normally sighted primary school children aged 4-12 years old the
      CR was determined both for distance and near vision. The examinations were
      performed using commonly available test charts based on the LEA symbols. RESULTS:
      At near, the CR was significantly better than at distance and for all ages <2.0.
      The upper limit of the CR at distance was <2.0 from age six. CONCLUSION: With
      commonly available tests the CR can easily be determined in school age children.
      For children >6 years of age, a CR > 2.0 (i.e. at least 3 lines difference
      between the result of a single optotype acuity test and a line acuity test) is
      suspicious and warrants further investigation. It may, for example, be a sign of
      cerebral visual impairment (CVI).

PMID- 22612353
TI  - Crowding in central vision in normally sighted and visually impaired [corrected]
      children aged 4 to 8 years: the influence of age and test design.
AB  - BACKGROUND/AIMS: To investigate crowding ratios in children with a visual
      impairment due to ocular disease (n = 58) and normally sighted children (n = 75)
      aged 4 to 8 years using several variants of two clinically available tests with
      different optotype spacing (fixed or proportional to the optotype size). METHODS:
      Crowding ratios, calculated by dividing the single acuity by the linear acuity,
      were measured binocularly with the C-test and the LH line chart. Ratios >1.00
      indicate crowding. RESULTS: The charts with fixed spacing revealed significantly
      higher crowding ratios for visually impaired children than normally sighted
      children (both for measurements at 40 cm and 5 m). The age-related reduction of
      the crowding ratios seen in normally sighted children when tested with near
      vision charts with fixed spacing was not present in the visually impaired group.
      Visually impaired children with nystagmus showed higher crowding ratios than
      visually impaired children without nystagmus. The chart with proportional
      intersymbol spacing (ISS) did not reveal differences between the normally sighted
      and visually impaired children; nor did it show group, age, or nystagmus effects.
      CONCLUSION: Visually impaired children showed higher crowding ratios than
      normally sighted children when measured with charts with fixed ISS. This study
      illustrates that test design and target/flanker interference as a manifestation
      of crowding are critical issues to bear in mind when assessing crowding ratios in
      children.

PMID- 22612354
TI  - Profile of visual functioning as a bridge between education and medicine in the
      assessment of impaired vision.
AB  - PURPOSE: To report on the development of the Profile of Visual Functioning as a
      framework for information exchange between schools and medical specialists
      involved in the education or care of children with impaired vision due to brain
      damage. METHODS: The role of vision loss in a child's functioning can be in part
      assessed by medical services, but in order to meet the needs of early
      intervention and education, numerous activities and tasks need to be observed
      during therapies, early intervention activities, and at local and special
      schools. RESULT: Information on vision loss can be gathered effectively and
      shared between medicine and education using well-structured lists of the most
      important functions, the Profile of Visual Functioning. We describe a common type
      of list of vision-related functions and activities. DISCUSSION: Cooperation
      between education and medicine requires development of a common language and
      agreements on how the large amount of information is collected. A basic list of
      measurements and observations covers functions of most children and thus gives a
      firm structure to the information exchange. CONCLUSIONS: Lists of functions to be
      examined and activities to be observed, if used by all stakeholders, may improve
      the quality of assessments for early intervention and special education. At the
      same time, schools and hospitals need to jointly arrange further education so
      that the names of activities start to make sense to doctors and the medical terms
      to teachers.

PMID- 22612355
TI  - The dynamic landscape of exceptional language development.
AB  - Developmental neurocognitive studies have shown that the brain systems supporting
      the emergence of sensory and cognitive abilities display different profiles of
      neuroplasticity. The research question posed here is to what extent sensory
      deprivation influences the dynamics of language development. The findings
      reported are grounded in studies with vision-impaired children with sighted peers
      featured as controls (age range 18 months to 3 years). Their data are matched
      against findings on advanced language development in blind children (age range:
      from 6 to 10 years; N = 12) and hearing-impaired and deaf children (age range:
      from 5 to 11 years; N = 20). The data give evidence that language acquisition in
      sensory-impaired children follows the same overall developmental path with
      respect to macrostructural changes and the succession of phase-shifts. System
      specific temporal discrepancies expressed in protracted phase-shifts and delayed
      increases of variability are most evident in the early phases. Self-organizing
      maps (SOMs) help to visualize individual and group-specific variation. The
      dynamic framework used (1) shows a higher sensibility to system-specific changes,
      (2) enhances the informative value of the data assessed, and (3) facilitates
      reliable prognoses concerning the child's cognitive and linguistic future.

PMID- 22612356
TI  - Ocular abnormalities and systemic disease in Down syndrome.
AB  - INTRODUCTION: Ocular problems as refractive errors, strabismus, accommodation,
      and cataract are well known in children with Down syndrome (DS). However, there
      is little information on the possible correlation of eye problems with systemic
      diseases such as heart defect (with or without surgery), hypotony,
      hypothyroidism, hearing loss, and others. METHODS: Ophthalmic problems versus
      certain systemic diseases were studied in 65 children with DS, aged 2 months to
      13 years, referred to the University Eye Hospital Ljubljana, Slovenia from 2008
      to 2010. Standard ophthalmic examination methods were used, and physical data
      were taken from pediatric records. RESULTS: Ocular findings included nystagmus
      (29.2%), esotropia (26.1%), epiphora (21.5%), Brushfield spots (16.9%), lens
      opacities (12.3%), abnormalities of the retinal vessels, foveal hypoplasia, or
      retinal pigment epithelium hyperplasia (32.2%), and optic disc pallor (7.6%).
      Hyperopia (36.9%) was the most frequent refractive error in the group, followed
      by astigmatism (29.2%) and myopia (24.6%). No diagnosed systemic abnormalities
      were found in 18.3% of the children, while 30.7% had congenital heart defect.
      Hypothyroidism, hypotony, hearing loss, gastrointestinal tract malformations, and
      leukemia were less common. Nystagmus was related to myopia and esotropia, and to
      heart disease and heart operations. CONCLUSIONS: Comorbidities are common in DS
      and complicate diagnosis, development, and therapy.

PMID- 22612357
TI  - Diagnosing cerebral visual impairment in children with good visual acuity.
AB  - PURPOSE: To identify elements that could facilitate the diagnosis of cerebral
      visual impairment (CVI) in children with good visual acuity in the general
      ophthalmic clinic. METHODS: We retrospectively investigated the clinical
      characteristics of 30 children with good visual acuity and CVI and compared them
      with those of 23 children who were referred with a suspicion of CVI, but proved
      to have a different diagnosis. Clinical characteristics included medical history,
      MRI findings, visual acuity, crowding ratio (CR), visual field assessment, and
      the results of ophthalmologic and orthoptic examination. We also evaluated the
      additional value of a short CVI questionnaire. RESULTS: Eighty-three percent of
      the children with an abnormal medical history (mainly prematurity and perinatal
      hypoxia) had CVI, in contrast with none of the children with a normal medical
      history. Cerebral palsy, visual field defects, and partial optic atrophy only
      occurred in the CVI group. 41% of the children with CVI had a CR >=2.0, which may
      be related to dorsal stream dysfunction. All children with CVI, but also 91% of
      the children without CVI gave >=3 affirmative answers on the CVI questionnaire.
      CONCLUSION: An abnormal pre- or perinatal medical history is the most important
      risk factor for CVI in children, and therefore in deciding which children should
      be referred for further multidisciplinary assessment. Additional symptoms of
      cerebral damage, i.e., cerebral palsy, visual field defects, partial optic
      atrophy, and a CR >=2 may support the diagnosis. CVI questionnaires should not be
      used for screening purposes as they yield too many false positives.

PMID- 22612358
TI  - The contents of the opticorum libri sex.

PMID- 22612359
TI  - Groundwater remediation: the next 30 years.
AB  - Groundwater remediation technologies are designed, installed, and operated based
      on the conceptual models of contaminant hydrogeology that are accepted at that
      time. However, conceptual models of remediation can change as new research, new
      technologies, and new performance data become available. Over the past few years,
      results from multiple-site remediation performance studies have shown that
      achieving drinking water standards (i.e., Maximum Contaminant Levels, MCLs) at
      contaminated groundwater sites is very difficult. Recent groundwater research has
      shown that the process of matrix diffusion is one key constraint. New
      developments, such as mass discharge, orders of magnitude (OoMs), and SMART
      objectives are now being discussed more frequently by the groundwater remediation
      community. In this paper, the authors provide their perspectives on the existing
      "reach MCLs" approach that has historically guided groundwater remediation
      projects, and advocate a new approach built around the concepts of OoMs and mass
      discharge.

PMID- 22612361
TI  - Is live high-train low altitude training relevant for elite athletes with already
      high total hemoglobin mass?

PMID- 22612360
TI  - Validity and variability of the 5-repetition sit-to-stand test in patients with
      multiple sclerosis.
AB  - PURPOSE: To investigate; (i) the relationship between the 5STS-test and lower
      extremity muscle strength and balance, and (ii) the variability of the 5STS-test
      in multiple sclerosis (MS) patients. METHOD: 22 MS patients were divided into two
      groups (Group A and Group B) who completed one 5STS familiarization test session
      and two testing sessions. In Group A, session 1 also included assessment of lower
      extremity muscle strength. Session 2 and 3 involved completion of two 5STS-tests
      and assessment of balance. In Group B, session 2 and 3 involved completion of two
      rounds of two 5STS-tests separated by a 30 min break. RESULTS: Significant
      correlations were found between the 5STS-test and isometric and isokinetic knee
      flexor and extensor muscle strength of the most affected leg (R = -0.60 to 
      0.77), and between the 5STS-test and balance performance (R = 0.69). Intra
      assessor day-to-day variability, intra-assessor test-retest variability and intra
      assessor variability within test were 25.5, 22.3, and 23.1%, respectively. Inter
      assessor variability within test and inter-assessor variability were 23.4 and
      5.9%, respectively. CONCLUSIONS: The 5STS-test is related to lower extremity
      muscle strength and to balance performance in MS patients. For interventional
      purposes, a change of >25% can be regarded as a real change.

PMID- 22612362
TI  - Reduction in plasma leucine after sprint exercise is greater in males than in
      females.
AB  - There is a pronounced gender difference in the accumulation of plasma ammonia
      after sprint exercise. Ammonia is a key intermediate in amino acid metabolism,
      which implies that gender-related differences in plasma and muscle amino acid
      concentrations after sprint exercise exist. To study this, three bouts of 30-s
      sprint exercise were performed by healthy females (n=8) and males (n=6). Blood
      leucine and muscle leucine were collected over the exercise period. Basal
      arterial plasma and skeletal muscle leucine were 40% higher in males than females
      (P<0.010 and P<0.020). Plasma, but not muscle, leucine decreased by sprint
      exercise and more so in males than females (g * t: P=0.025). Increase in ammonia
      was higher in males than females in both plasma and muscle (g * t: P<0.001 and
      P=0.003). An opposite pattern was shown for plasma glutamine, where an increase
      was found in females (P<0.001), but not in males. In conclusion, the lower plasma
      ammonia after sprint exercise in females seems to be explained by a lower
      accumulation of ammonia in skeletal muscle and by a buffering of ammonia in the
      form of glutamine in females. The greater reduction in plasma leucine in males
      seems to be related to their greater increase in muscle ammonia after sprint
      exercise.

PMID- 22612363
TI  - Boosting mitochondrial biogenesis or protein synthesis in human skeletal muscle:
      Novel insights.

PMID- 22612365
TI  - Role of space provision in regeneration of localized two-wall intrabony defects
      using periosteal pedicle graft as an autogenous guided tissue membrane.
AB  - BACKGROUND: Marginal pedicle periosteum (MPP) has been used as a rigid membrane
      in guided tissue regeneration (GTR) for osseous defects. The present study aims
      to study the effect of space provision by an alloplastic graft material in bone
      defect area (BDA) reduction of 2-wall defects. METHODS: Twenty interproximal
      intrabony 2-wall defects in healthy non-smoking patients with chronic
      periodontitis were randomly divided in control (group 1, periosteum alone) and
      experimental (group 2, periosteum with alloplastic graft material) groups.
      Measurements of probing depth (PD), clinical attachment level (CAL), and
      radiographic BDA were done at the baseline and 6-month postoperative evaluations.
      RESULTS: The 6-month postoperative assessment showed clinical and radiographic
      improvements with PD reduction, CAL gain, and changes in BDA in both groups,
      which was statistically significant compared with baseline (P <0.05). However,
      BDA reduction was statistically greater in group 2 (48.88% +/- 18.61%) compared
      with group 1 (14.08% +/- 12.97%) at the 6-month follow-up (P = 0.009).
      CONCLUSION: Within the limitations of this study, it can be concluded that space
      provision by an alloplastic graft material increases the regenerative potential
      of MPP as a GTR membrane and results in increased defect fill.

PMID- 22612364
TI  - Platelet-derived growth factor promotes periodontal regeneration in localized
      osseous defects: 36-month extension results from a randomized, controlled, double
      masked clinical trial.
AB  - BACKGROUND: Recombinant human platelet-derived growth factor (rhPDGF) is safe and
      effective for the treatment of periodontal defects in short-term studies up to 6
      months in duration. We now provide results from a 36-month extension study of a
      multicenter, randomized, controlled clinical trial evaluating the effect and long
      term stability of PDGF-BB treatment in patients with localized severe periodontal
      osseous defects. METHODS: A total of 135 participants were enrolled from six
      clinical centers for an extension trial. Eighty-three individuals completed the
      study at 36 months and were included in the analysis. The study investigated the
      local application of beta-tricalcium phosphate scaffold matrix with or without
      two different dose levels of PDGF (0.3 or 1.0 mg/mL PDGF-BB) in patients
      possessing one localized periodontal osseous defect. Composite analysis for
      clinical and radiographic evidence of treatment success was defined as percentage
      of cases with clinical attachment level (CAL) >=2.7 mm and linear bone growth
      (LBG) >=1.1 mm. RESULTS: The participants exceeding this composite outcome
      benchmark in the 0.3 mg/mL rhPDGF-BB group went from 62.2% at 12 months, 75.9% at
      24 months, to 87.0% at 36 months compared with 39.5%, 48.3%, and 53.8%,
      respectively, in the scaffold control group at these same time points (P <0.05).
      Although there were no significant increases in CAL and LBG at 36 months among
      all groups, there were continued increases in CAL gain, LBG, and percentage bone
      fill over time, suggesting overall stability of the regenerative response.
      CONCLUSION: PDGF-BB in a synthetic scaffold matrix promotes long-term stable
      clinical and radiographic improvements as measured by composite outcomes for CAL
      gain and LBG for patients possessing localized periodontal defects (
      ClinicalTrials.gov no. CT01530126).

PMID- 22612366
TI  - Elevated levels of a disintegrin and metalloproteinase 8 in gingival crevicular
      fluid of patients with periodontal diseases.
AB  - BACKGROUND: A disintegrin and metalloproteinase 8 (ADAM8) is involved in
      inflammation and is essential for osteoclastogenesis. Elevated ADAM8 levels are
      detected in human serum and other body fluids in several inflammatory conditions.
      Therefore, we hypothesized that ADAM8 levels are also raised in gingival
      crevicular fluid (GCF) of patients with periodontal diseases. METHODS: Forty-five
      patients with periodontal diseases (n = 15 for each group: the group of patients
      with gingivitis, the group with aggressive periodontitis [AgP], and the group
      with chronic periodontitis [CP]) and 15 volunteers who exhibited healthy gingiva
      were recruited. Four periodontal parameters, gingival index, plaque index,
      probing depth, and clinical attachment level, were recorded before GCF
      collection. The presence of ADAM8 in GCF was shown by immunoblotting using anti
      human ADAM8 polyclonal antibody against its prodomain, and the ADAM8 levels were
      measured by an enzyme-linked immunosorbent assay. RESULTS: Four immunoreactive
      bands at 120, 70, 50, and <30 kDa were detected in the groups of patients with
      periodontitis, whose intensities were stronger than those in the group of
      patients with gingivitis, consistent with significantly greater ADAM8 levels in
      both groups of patients, with either CP or AgP, than those in the group of
      patients with gingivitis and in the group that was healthy (P <0.001). Moreover,
      the ADAM8 levels correlated significantly with the four periodontal parameters (P
      <0.001), indicating that ADAM8 levels are positively associated with the degree
      of periodontal tissue inflammation and destruction. CONCLUSIONS: The ADAM8 levels
      are elevated in the GCF of patients with periodontal diseases, including
      gingivitis, CP, and AgP, in comparison to control participants who are healthy,
      and they correlate with four clinical parameters that reflect the degree of
      disease severity.

PMID- 22612367
TI  - Stimulation of periodontal ligament stem cells by dentin matrix protein 1
      activates mitogen-activated protein kinase and osteoblast differentiation.
AB  - BACKGROUND: Periodontitis can ultimately result in tooth loss. Many natural and
      synthetic materials have been tried to achieve periodontal regeneration, but the
      results remain variable and unpredictable. We hypothesized that exogenous
      treatment with dentin matrix protein 1 (DMP1) activates specific genes and
      results in phenotypic and functional changes in human periodontal ligament stem
      cells (hPDLSCs). METHODS: hPDLSCs were isolated from extracted teeth and cultured
      in the presence or absence of DMP1. Quantitative polymerase chain reactions were
      performed to analyze the expression of several genes involved in periodontal
      regeneration. hPDLSCs were also processed for immunocytochemical and Western blot
      analysis using phosphorylated extracellular signal-regulated kinase (pERK) and
      ERK antibodies. Alkaline phosphatase and von Kossa staining were performed to
      characterize the differentiation of hPDLSCs into osteoblasts. Field emission
      scanning electron microscopic analysis of the treated and control cell cultures
      were also performed. RESULTS: Treatment with DMP1 resulted in the upregulation of
      genes, such as matrix metalloproteinase-2, alkaline phosphatase, and transforming
      growth factor beta1. Activation of ERK mitogen-activated protein kinase signaling
      pathway and translocation of pERK from the cytoplasm to the nucleus was observed.
      Overall, DMP1-treated cells showed increased expression of alkaline phosphatase,
      increased matrix, and mineralized nodule formation when compared with untreated
      controls. CONCLUSION: DMP1 can orchestrate a coordinated expression of genes and
      phenotypic changes in hPDLSCs by activation of the ERK signaling pathway, which
      may provide a valuable strategy for tissue engineering approaches in periodontal
      regeneration.

PMID- 22612368
TI  - Comparative study of Chinese hamster ovary cell versus Escherichia coli-derived
      bone morphogenetic protein-2 using the critical-size supraalveolar peri-implant
      defect model.
AB  - BACKGROUND: Chinese hamster ovary (CHO) cell-derived recombinant human bone
      morphogenetic protein-2 (rhBMP-2) has been introduced for spine, long bone, and
      craniofacial indications. Escherichia coli- (E. coli) derived rhBMP-2 displays
      comparable efficacy to CHO cell-derived rhBMP-2 in vitro and in small-animal
      models. The objective of this study is to evaluate the efficacy of E. coli
      derived rhBMP-2 compared to the benchmark CHO cell-derived rhBMP-2 using an
      established large-animal model. METHODS: Contralateral, critical-size
      supraalveolar peri-implant defects in six adult male Hound Labrador mongrel dogs
      received CHO cell- or E. coli-derived rhBMP-2 (0.2 mg/mL) in an absorbable
      collagen sponge (ACS) carrier. In each quadrant, three dental implants were
      placed. A titanium mesh device was used to support space provision. The animals
      received fluorescent bone markers for qualitative evaluations. Animals were
      euthanized at 8 weeks for histopathologic and histometric evaluation. RESULTS:
      Clinical healing included significant swelling, but none of the animals
      experienced wound dehiscences. CHO cell- and E. coli-derived rhBMP-2 supported
      comparable bone formation (new bone area, 35.8 +/- 3.6 versus 30.1 +/- 2.2 mm(2);
      bone density, 31.8% +/- 1.6% versus 35.6% +/- 2.5%; and osseointegration, 32.9%
      +/- 7.4% versus 33.7% +/- 8.1%) without statistically significant differences
      between treatments. Newly formed immature delicate trabecular bone in
      fibrovascular marrow filled the space underneath the titanium mesh and extended
      coronally above the mesh. Seroma formation was frequently observed. There were no
      discernable qualitative histologic differences between treatments. CONCLUSION:
      CHO cell- and E. coli-derived rhBMP-2 in an ACS carrier appear equally effective
      at inducing local bone formation in support of dental implant osseointegration.

PMID- 22612369
TI  - The clinical effect of scaling and root planing and the concomitant
      administration of systemic amoxicillin and metronidazole: a systematic review.
AB  - BACKGROUND: The treatment of periodontitis frequently begins with a non-surgical
      phase that includes scaling and root planing (SRP) and, on occasion, the use of
      systemic antibiotics. The goal of this review is to systematically evaluate the
      data concerning the effect of the concomitant administration of amoxicillin and
      metronidazole adjunctive to SRP in adults who are otherwise healthy. METHODS: The
      PubMed-MEDLINE, Cochrane-Central, and EMBASE databases were searched to April 1,
      2012, to identify appropriate studies. Probing depth (PD), clinical attachment
      level (CAL), bleeding on probing, and plaque index were selected as outcome
      variables. Based on the extracted mean values and number of individuals, changes
      in weighted means were calculated and a meta-analysis conducted. RESULTS: The
      search yielded 526 unique titles and abstracts. Ultimately, 35 studies were
      selected, describing 28 clinical trials meeting the eligibility criteria. The
      full-mouth weighted mean change for PD showed an improvement of 1.41 mm. The full
      mouth weighted mean change for CAL showed a gain of 0.94 mm. CONCLUSION: Systemic
      antimicrobial therapy using a combination of amoxicillin and metronidazole as an
      adjunct to SRP can enhance the clinical benefits of non-surgical periodontal
      therapy in adults who are otherwise healthy.

PMID- 22612370
TI  - A systematic review of the use of growth factors in human periodontal
      regeneration.
AB  - BACKGROUND: There is a large body of evidence using cells and animal models
      demonstrating the effectiveness of growth factors in periodontal regeneration.
      However, there appears to be minimal literature comparing the efficacy of growth
      factors in human periodontal regeneration compared to other techniques and
      procedures. Therefore, the aim of this study is to perform a systematic review of
      human studies using growth factors for periodontal regeneration and to compare
      the efficacy of these growth factors to other accepted techniques for periodontal
      regeneration. METHODS: An electronic and manual search based on agreed search
      phrases between the primary investigator and a secondary investigator was
      performed to identify the use of growth factors in periodontics for the
      literature review. The articles that were identified by this systematic review
      were analyzed in detail, which included the study of their inclusion and
      exclusion criteria, outcome measures determination and analysis, risk of bias,
      adverse events, and conclusions or inference of the efficacy of growth factors to
      the general population. RESULTS: Five papers fulfilled the inclusion criteria.
      Two papers were identified that had sufficiently similar study design that a meta
      analysis of their outcomes was possible. Most of the reported outcomes from the
      selected papers were descriptive. The articles demonstrated periodontal
      regeneration at least comparable to their respective positive controls, with only
      a couple of articles demonstrating significantly greater outcomes compared to
      their respective positive controls. Histologic evidence demonstrated greater
      periodontal regeneration when using growth factors compared to other regenerative
      techniques and an increased healing and bone maturation rate compared to other
      regenerative and bone augmentation techniques in these human studies.
      CONCLUSIONS: Within the limits of this systematic review, the use of recombinant
      human platelet-derived growth factor-BB (rhPDGF-BB) led to greater clinical
      attachment level gain of ~1 mm compared to an osteoconductive control, beta
      tricalcium phosphate (beta-TCP). The use of rhPDGF-BB led to greater percentage
      bone fill of ~40% compared to the osseoconductive control, beta-TCP. Last, the
      use of rhPDGF-BB led to an increased rate of bone growth of ~2 mm compared to the
      osseoconductive control, beta-TCP.

PMID- 22612371
TI  - Enamel matrix derivative, alone or associated with a synthetic bone substitute,
      in the treatment of 1- to 2-wall periodontal defects.
AB  - BACKGROUND: In this study, we compare the effects of enamel matrix derivative
      (EMD) associated with a hydroxyapatite and beta-tricalcium phosphate (HA/beta
      TCP) implant to EMD alone and to open-flap debridement (OFD) when surgically
      treating 1- to 2-wall intrabony defects. METHODS: Thirty-four patients,
      exhibiting >=3 intraosseous defects in different quadrants, were each treated by
      OFD, EMD, or EMD + HA/beta-TCP in each defect. At baseline and 12 and 24 months,
      a complete clinical and radiographic examination was done. Pre-therapy and post
      therapy clinical (probing depth [PD], clinical attachment level [CAL], and
      gingival recession [GR]) and radiographic (defect bone level [DBL] and
      radiographic bone gain [RBG]) parameters for the different treatments were
      compared. RESULTS: After 12 and 24 months, almost all the clinical and
      radiographic parameters showed significant changes from baseline within each
      group (P <0.001). Differences in PD, CAL, and DBL scores were also seen among the
      three groups at the 12- and 24-month visits (P <0.001). At 12 and 24 months after
      treatment, the EMD + HA/beta-TCP group showed significantly greater PD reduction
      (4.00 +/- 0.42 mm; 4.25 +/- 0.63 mm), CAL gain (3.47 +/- 0.65 mm; 3.63 +/- 0.91
      mm), and RBG (3.17 +/- 0.69 mm; 3.35 +/- 0.80 mm) and less GR increase (0.56 +/-
      0.37 mm; 0.63 +/- 0.42 mm) compared with the OFD and EMD groups (P <0.05).
      CONCLUSION: Our data support the hypothesis that the adjunct of an HA/beta-TCP
      composite implant with EMD may improve the clinical and radiographic outcomes of
      the surgical treatment of unfavorable intrabony defects.

PMID- 22612372
TI  - Social learning in humans and nonhuman animals: theoretical and empirical
      dissections.
AB  - The past decade has seen a resurgent, concerted interest in social learning
      research comparing human and nonhuman animals. In this special issue, we present
      a synthesis of work that consolidates what is currently known and provides a
      platform for future research. Consequently, we include both new empirical studies
      and novel theoretical proposals describing work with both human children and
      adults and a range of nonhuman animals. In this introduction, we describe the
      background of this special issue and provide a context for each of the eight
      articles it contains. We hope such introduction will not only help the reader
      synthesize the interdisciplinary views that characterize this broad field, but
      also stimulate development of new methods, concepts, and data.

PMID- 22612376
TI  - Prior varicella zoster virus exposure in IBD patients treated by anti-TNFs and
      other immunomodulators: implications for serological testing and vaccination
      guidelines.
AB  - BACKGROUND: Varicella zoster virus (VZV) is a severe and preventable infection in
      immunosuppressed IBD patients. ECCO guidelines recommend VZV immunisation in
      patients with negative VZV exposure history. The value of patient-reported VZV
      exposure history for prediction of seropositivity in IBD patients remains
      unknown. Moreover, data on VZV immunity in adult IBD patients or accuracy of VZV
      serological testing under immunomodulator treatment is sparse. AIMS: The primary
      aim was to determine the prevalence of seropositivity for VZV-IgG in
      immunomodulator-treated IBD patients. A secondary aim was to establish the value
      of patient-reported history of past VZV infection for prediction of immunity, to
      validate the current vaccination strategy. METHODS: History of VZV-related
      illness was accessed by epidemiological questionnaire, and serological testing
      for VZV-IgG was performed. Serum anti-TNF medications levels were measured when
      applicable. RESULTS: One hundred twenty one IBD (86% Crohn's disease, mean age 37
      +/- 12.8) patients were included in the study. Immunomodulator therapy was
      received by 87% (anti-TNFs- 71%) of the patients. Previous exposure to VZV was
      reported by 104 patients, and 97/104 (93%) were VZV-IgG seropositive. Seventeen
      patients, all seropositive, reported negative exposure history. The calculated
      positive and negative predictive values for the reported history of VZV exposure
      were 93% and 0% respectively. CONCLUSIONS: Negative history of VZV exposure is a
      poor predictor of seronegativity. History-positive patients may still be
      seronegative and exposed to VZV infection. We suggest serological testing of all
      IBD patients with subsequent immunisation of the seronegative patients before
      initiation of immunosuppressive therapy.

PMID- 22612377
TI  - Locally released small (non-protein) ninhydrin-reacting molecules underlie
      developmental differences of cultured medullary versus spinal dorsal horn
      neurons.
AB  - Neurons located in the trigeminal subnucleus caudalis (Vc) play crucial roles in
      pain and sensorimotor functions in the orofacial region. Because of many
      anatomical and functional similarities with the spinal dorsal horn (SDH), Vc has
      been termed the medullary dorsal horn--analogous to the SDH. Here, we report that
      when compared with embryonic SDH neurons in culture, neurons isolated from the Vc
      region showed significantly slower growth, lower glutamate receptor activity, and
      more cells undergoing cell death. SDH neuron development was inhibited in co
      cultures of SDH and Vc tissues while Vc neuron development was promoted by co
      culture with SDH tissues. Furthermore, we identified that small (non-protein)
      ninhydrin-reacting molecules purified from either embryonic or post-natal Vc
      conditioned medium inhibited neuronal growth whereas ninhydrin-reacting molecules
      from SDH-conditioned medium promoted neuronal growth. These findings suggest the
      involvement of locally released factors in the region-specific regulation of
      neuronal development in Vc and SDH, central nervous system regions playing
      critical roles in pain, and point to novel avenues for investigating central
      nervous system regionalization and for designing therapeutic approaches to manage
      neurodegenerative diseases and pain.

PMID- 22612378
TI  - A concept of thrombolysis as a corrosion-erosion process verified by optical
      microscopy.
AB  - OBJECTIVE: Outcome of the thrombolytic treatment is dependent on biochemical
      reactions of the fibrinolytic system as well as on hemodynamic conditions.
      However, understanding of the interaction between these two processes is still
      deficient. METHODS: Model blood clot thrombolysis in an artificial perfusion
      system was studied by stroboscopic optical microscopy. The obtained images were
      analyzed by particle-tracking software for clot size distributions of removed
      clot fragments, and for non-lysed blood clot areas as function of time. Based on
      the experimental results, a probabilistic phenomenological model of blood clot
      dissolution was developed, in which mechanical forces of streaming plasma are in
      balance with binding forces of blood cells to the remaining clot. RESULTS: The
      clot dissolution rate and maximum size of removed clot fragments were increased
      with greater flow rate. A 3.3-fold flow rate increase resulted in a two-fold clot
      dissolution rate increase, while sizes of the removed fragments were in the range
      of single blood cells, up to thousand-cell clusters. Our phenomenological
      microscale model of clot dissolution suggests that thrombolysis is a corrosion
      erosion-like process. CONCLUSIONS: The findings of this study provide a possible
      explanation for the origin of clot fragment formation in the blood clot
      dissolution process.

PMID- 22612380
TI  - Superoleophobic surfaces through control of sprayed-on stochastic topography.
AB  - The liquid repellency and surface topography characteristics of coatings
      comprising a sprayed-on mixture of fluoroalkyl-functional precipitated silica and
      a fluoropolymer binder were examined using contact and sliding angle analysis,
      electron microscopy, and image analysis for determination of fractal
      dimensionality. The coatings proved to be an especially useful class of liquid
      repellent materials due to their combination of simple and scalable deposition
      process, low surface energy, and the roughness characteristics of the aggregates.
      These characteristics interact in a unique way to prevent the buildup of binder
      in interstitial regions, preserving re-entrant curvature across multiple length
      scales, thereby enabling a wide range of liquid repellency, including
      superoleophobicity. In addition, rather than accumulating in the interstices, the
      binder becomes widely distributed across the surface of the aggregates, enabling
      a mechanism in which a simple shortage or excess of binder controls the extent of
      coating roughness at very small length scales, thereby controlling the extent of
      liquid repellence.

PMID- 22612379
TI  - Role of the blood-brain barrier in the evolution of feeding and cognition.
AB  - The blood-brain barrier (BBB) regulates the blood-to-brain passage of
      gastrointestinal hormones, thus informing the brain about feeding and nutritional
      status. Disruption of this communication results in dysregulation of feeding and
      body weight control. Leptin, which crosses the BBB to inform the CNS about
      adiposity, provides an example. Impaired leptin transport, especially coupled
      with central resistance, results in obesity. Various substances/conditions
      regulate leptin BBB transport. For example, triglycerides inhibit leptin
      transport. This may represent an evolutionary adaptation in that
      hypertriglyceridemia occurs during starvation. Inhibition of leptin, an
      anorectic, during starvation could have survival advantages. The large number of
      other substances that influence feeding is explained by the complexity of
      feeding. This complexity includes cognitive aspects; animals in the wild are
      faced with cost/benefit analyses to feed in the safest, most economical way. This
      cognitive aspect partially explains why so many feeding substances affect
      neurogenesis, neuroprotection, and cognition. The relation between triglycerides
      and cognition may be partially mediated through triglyceride's ability to
      regulate the BBB transport of cognitively active gastrointestinal hormones such
      as leptin, insulin, and ghrelin.

PMID- 22612381
TI  - Effects of ergot alkaloids on liver function of piglets can be detected by the
      [(13)C]methacetin breath test irrespective of oral or intramuscular route of
      tracer administration.
AB  - Ergot alkaloids (sum=total alkaloids, TA) originate from the phyto-pathogenic
      fungus Claviceps purpurea and might exert feed intake depressing and hepatotoxic
      effects on animals. The aim of the study was to evaluate TA effects on
      performance and liver function of piglets with the [(13)C]methacetin breath test
      and two routes of tracer administration (orally, p.o.; intramuscularly, i.m.).
      Two ergot batches were mixed into piglet diets resulting in 21 and 17 mg TA kg(
      1) (Ergot-5 and -12, respectively) and compared with an ergot-free control diet.
      Feed intake was significantly depressed after feeding the ergot containing diets
      (p=<0.001). The time at maximum (13)CO(2) exhalation (t (max)) and the half-life
      (t (0.5)) were not influenced by treatments and varied between 25 and 68 min
      after the p.o., and 28 and 62 min after the i.m. administration of
      [(13)C]methacetin, respectively. The cumulative (13)C recovery (cPDR(30)) was
      significantly lower due to feeding the diet Ergot-5 (6.6 %) compared with the
      Ergot-12 (8.8 %) and the control diet (9.7 %) irrespective of the route of tracer
      administration (p=0.044). As a discrimination of the diet effects through both
      tracer administration routes is possible, the i.m. application should be
      preferred in piglets as this causes less stress than the oral forced
      administration.

PMID- 22612382
TI  - Oligonucleotide and polymer functionalized nanoparticles for amplification-free
      detection of DNA.
AB  - Sensitive and quantitative nucleic acid testing from complex biological samples
      is now an important component of clinical diagnostics. Whereas nucleic acid
      amplification represents the gold standard, its utility in resource-limited and
      point-of-care settings can be problematic due to assay interferants, assay time,
      engineering constraints, and costs associated with both wetware and hardware. In
      contrast, amplification-free nucleic acid testing can circumvent these
      limitations by enabling direct target hybridization within complex sample
      matrices. In this work, we grew random copolymer brushes from the surface of
      silica-coated magnetic nanoparticles using azide-modified and hydroxyl oligo
      ethylene glycol methacrylate (OEGMA) monomers. The azide-functionalized polymer
      brush was first conjugated, via copper-catalyzed azide/alkyne cycloaddition
      (CuAAC), with herpes simplex virus (HSV)-specific oligonucleotides and then with
      alkyne-substituted polyethylene glycol to eliminate all residual azide groups.
      Our methodology enabled control over brush thickness and probe density and
      enabled multiple consecutive coupling reactions on the particle grafted brush.
      Brush- and probe-modified particles were then combined in a 20 min hybridization
      with fluorescent polystyrene nanoparticles modified with HSV-specific reporter
      probes. Following magnetic capture and washing, the particles were analyzed with
      an aggregate fluorescence measurement, which yielded a limit of detection of 6 pM
      in buffer and 60 pM in 50% fetal bovine serum. Adoption of brush- and probe
      modified particles into a particle counting assay will result in the development
      of diagnostic assays with significant improvements in sensitivity.

PMID- 22612383
TI  - Metabolite identification using automated comparison of high-resolution
      multistage mass spectral trees.
AB  - Multistage mass spectrometry (MS(n)) generating so-called spectral trees is a
      powerful tool in the annotation and structural elucidation of metabolites and is
      increasingly used in the area of accurate mass LC/MS-based metabolomics to
      identify unknown, but biologically relevant, compounds. As a consequence, there
      is a growing need for computational tools specifically designed for the
      processing and interpretation of MS(n) data. Here, we present a novel approach to
      represent and calculate the similarity between high-resolution mass spectral
      fragmentation trees. This approach can be used to query multiple-stage mass
      spectra in MS spectral libraries. Additionally the method can be used to
      calculate structure-spectrum correlations and potentially deduce substructures
      from spectra of unknown compounds. The approach was tested using two different
      spectral libraries composed of either human or plant metabolites which currently
      contain 872 MS(n) spectra acquired from 549 metabolites using Orbitrap FTMS(n).
      For validation purposes, for 282 of these 549 metabolites, 765 additional
      replicate MS(n) spectra acquired with the same instrument were used. Both the
      dereplication and de novo identification functionalities of the comparison
      approach are discussed. This novel MS(n) spectral processing and comparison
      approach increases the probability to assign the correct identity to an
      experimentally obtained fragmentation tree. Ultimately, this tool may pave the
      way for constructing and populating large MS(n) spectral libraries that can be
      used for searching and matching experimental MS(n) spectra for annotation and
      structural elucidation of unknown metabolites detected in untargeted metabolomics
      studies.

PMID- 22612384
TI  - Crystal structure of YbCu6In6 and mixed valence behavior of Yb in YbCu(6
      x)In(6+x) (x = 0, 1, and 2) solid solution.
AB  - High quality single crystals of YbCu(6)In(6) have been grown using the flux
      method and characterized by means of single crystal X-ray diffraction data.
      YbCu(6)In(6) crystallizes in the CeMn(4)Al(8) structure type, tetragonal space
      group I4/mmm, and the lattice constants are a = b = 9.2200(13) A and c =
      5.3976(11) A. The crystal structure of YbCu(6)In(6) is composed of pseudo-Frank
      Kasper cages filled with one ytterbium atom in each ring. The neighboring cages
      share corners along [100] and [010] to build the three-dimensional network.
      YbCu(6-x)In(6+x) (x = 0, 1, and 2) solid solution compounds were obtained from
      high frequency induction heating and characterized using powder X-ray
      diffraction. The magnetic susceptibilities of YbCu(6-x)In(6+x) (x = 0, 1, and 2)
      were investigated in the temperature range 2-300 K and showed Curie-Weiss law
      behavior above 50 K, and the experimentally measured magnetic moment indicates
      mixed valent ytterbium. A deviation in inverse susceptibility data at 200 K
      suggests a valence transition from Yb(2+) to Yb(3+) as the temperature decreases.
      An increase in doping of Cu at the Al2 position enhances the disorder in the
      system and enhancement in the trivalent nature of Yb. Electrical conductivity
      measurements show that all compounds are of a metallic nature.

PMID- 22612385
TI  - The orphan receptor GPR3 modulates the early phases of cocaine reinforcement.
AB  - BACKGROUND AND PURPOSE: The modulatory activity of the orphan receptor GPR3 in
      the brain has been related to the control of emotional behaviours. Limbic
      structures that express GPR3 have been associated with the effects of drug abuse.
      EXPERIMENTAL APPROACH: The role of GPR3 in different cocaine-elicited behaviours
      including locomotor activity, behavioural sensitization, conditioned place
      preference (CPP) and intravenous self-administration was evaluated in Gpr3-/-
      mice and their Gpr3+/+ littermates. Cocaine-induced dopamine release in the
      nucleus accumbens was also evaluated to elucidate the effect of Gpr3 deletion on
      extracellular levels of dopamine. KEY RESULTS: Gpr3-/- mice exhibited higher
      rewarding responses in the CPP paradigm. Gpr3-/- mice self-administered more
      cocaine, especially during the first days of training. No differences were found
      between genotypes regarding behavioural sensitization and the maximal effort
      required to obtain a cocaine infusion. Non-contingent priming injections of
      cocaine before operant training eliminated enhanced cocaine self-administration
      in Gpr3-/- mice. Extracellular levels of dopamine in the nucleus accumbens
      induced by cocaine did not differ between genotypes. CONCLUSIONS AND
      IMPLICATIONS: The increased responsiveness of Gpr3-/- mice to the acute locomotor
      effects of cocaine and the inconsistency to further increase this effect
      reflected an 'already maximally sensitized' basal state. Enhanced responsiveness
      of Gpr3-/- mice to cocaine reward and to early phases of reinforcement suggests
      that an initial alteration increased vulnerability to this type of drug abuse.
      Overall, altered signalling pathways of GPR3 could contribute to the
      neurobiological substrate involved in developing addiction to cocaine.

PMID- 22612386
TI  - Analysis of enantioselective biochemical, physiological, and transcriptional
      effects of the chiral herbicide diclofop methyl on rice seedlings.
AB  - Diclofop methyl (DM) is a chiral herbicide that is widely used as a racemic
      mixture. This study analyzed the enantioselective effects of R- and S-DM on rice
      at the physiological and molecular levels. DM exerts an enantioselective effect
      on rice growth, reactive oxygen substance (ROS) formation, and antioxidant gene
      expression, with R-DM acting as a more potent stressor than S-DM. An analysis of
      chlorophyll fluorescence demonstrated that photosynthesis process was more
      strongly inhibited by R-DM than by S-DM. Microarray results showed that many
      metabolic pathways, including starch and sucrose metabolism, oxidative
      phosphorylation, and amino acid biosynthesis and metabolism, were affected by DM
      in an enantioselective manner. These results suggest that R-DM is more active to
      plant growth than S-DM and that this activity is induced not only by repression
      of fatty acid synthesis but also by R-DM affecting the transcription of genes in
      other metabolic pathways in an enantioselective manner.

PMID- 22612387
TI  - Who benefits from clinical supervision and how? The association between clinical
      supervision and the work-related well-being of female hospital nurses.
AB  - AIM AND OBJECTIVES: The aims of this study were (1) to identify which nurses
      benefitted most from clinical supervision and (2) to explore whether they were
      healthier and more satisfied with their work than their peers who did not attend
      clinical supervision. BACKGROUND: To maintain quality nursing, there is currently
      a social call to improve the well-being of nurses at work. Restoring nurses' well
      being is one of the main purposes of clinical supervision. However, research
      evidence on the effects of clinical supervision is scarce. DESIGN: Survey.
      METHODS: Questionnaires were distributed to female hospital nurses (n=304), about
      a half of whom (48.7%) had attended clinical supervision. Perceptions of work and
      health among the nurses who gave the best evaluations of clinical supervision
      (n=74) were compared with those of their peers who gave the worst evaluations
      (n=74) or who had not attended clinical supervision (n=156). RESULTS: The nurses
      who received efficient clinical supervision reported more job and personal
      resources and were more motivated and committed to the organisation than their
      peers. However, professional inefficacy was the only burnout dimension on which
      they scored lower than other nurses. CONCLUSIONS: Clinical supervision can be
      conceptualised as an additional job resource associated with other job and
      personal resources, which mutually reinforce each other, promoting well-being at
      work. Efficient clinical supervision is probably both an antecedent as well as a
      consequence of well-being at work. RELEVANCE TO CLINICAL PRACTICE: The results of
      this study advocate management planning to provide formal support for health care
      providers. Medical-surgical nurses are interested in clinical supervision.
      Reflecting on practice in clinical supervision generates new ideas about how to
      improve the quality of care and the psychosocial work environment. However,
      clinical supervision may be viewed as a preventive method rather than a treatment
      for burnout.

PMID- 22612389
TI  - Malocclusion and oral health-related quality of life in Brazilian school
      children.
AB  - OBJECTIVE: To test the hypothesis that malocclusion and its impact on quality of
      life has no effect on 8- to 10-year-old Brazilian schoolchildren as measured by
      an oral health-related quality of life (OHRQoL) instrument. MATERIALS AND
      METHODS: A cross-sectional study was carried out with a population-based sample
      of 1204 8- to 10-year-old children attending elementary schools in Belo
      Horizonte, Brazil. Dental examinations were carried out by two calibrated
      examiners. OHRQoL was assessed using the Brazilian version of the Child
      Perceptions Questionnaire. The Dental Aesthetic Index was used for the clinical
      assessment of malocclusion. Dental caries and socioeconomic factors were used as
      controlling variables. Bivariate analysis involved the chi-square test and the
      Fisher exact test. A Poisson regression model was employed for the multivariate
      analysis (P < .05). RESULTS: Anterior segment spacing and anterior mandibular
      overjet were significantly associated with impact on OHRQoL (P < .05).
      Schoolchildren with malocclusion were 1.30-fold (95% CI: 1.15-1.46; P < 0.001)
      more likely to experience a negative impact on OHRQoL than those without
      malocclusion. Children belonging to families with an income less than or equal to
      two times the minimum wage were 1.59-fold (95% CI: 1.35-1.88; P < 0.001) more
      likely to experience a negative impact on OHRQoL than those belonging to families
      with the highest income. CONCLUSIONS: Schoolchildren with malocclusion from lower
      income families experience a greater negative impact on OHRQoL.

PMID- 22612390
TI  - Measurement accuracy with a new dental panoramic radiographic technique based on
      tomosynthesis.
AB  - OBJECTIVE: To investigate measurement errors and head positioning effects on
      radiographs made with new dental panoramic radiograph equipment that uses
      tomosynthesis. MATERIALS AND METHODS: Radiographic images of a simulated human
      head or phantom were made at standard head positions using the new dental
      panoramic radiograph equipment. Measurement errors were evaluated by comparing
      with the true values. The phantom was also radiographed at various alternative
      head positions. Significant differences between measurement values at standard
      and alternative head positions were evaluated. Magnification ratios of the
      dimensions at standard and alternative head positions were calculated. RESULTS:
      The measurement errors were small for all dimensions. On the measurements at 4-mm
      displacement positions, no dimension was significantly different from the
      standard value, and all dimensions were within +/-5% of the standard values. At
      12-mm displacement positions, the magnification ratios for tooth length and
      mandibular ramus height were within +/-5% of the standard values, but those for
      dental arch width, mandibular width, and mandibular body length were beyond +/-5%
      of the standard values. CONCLUSIONS: Measurement errors on radiographs made using
      the new panoramic radiograph equipment were small in any direction. At 4-mm head
      displacement positions, no head positioning effect on the measurements was found.
      At 12-mm head displacement positions, the measurements for vertical dimensions
      were little affected by head positioning, while those for lateral and
      anteroposterior dimensions were strongly affected.

PMID- 22612388
TI  - Optimising an escalating shockwave amplitude treatment strategy to protect the
      kidney from injury during shockwave lithotripsy.
AB  - Study Type--Therapy (case series) Level of Evidence 4. What's known on the
      subject? and What does the study add? Animal studies have shown that one approach
      to reduce SWL-induced renal injury is to pause treatment for 3-4 min early in the
      SWL-treatment protocol. However, there is typically no pause in treatment during
      clinical lithotripsy. We show in a porcine model that a pause in SWL treatment is
      unnecessary to achieve a reduction in renal injury if treatment is begun at a low
      power setting that generates low-amplitude SWs, and given continuously for ~ 4
      min before applying higher-amplitude SWs. OBJECTIVE: * To test the idea that a
      pause (~ 3 min) in the delivery of shockwaves (SWs) soon after the initiation of
      SW lithotripsy (SWL) is unnecessary for achieving a reduction in renal injury, if
      treatment is begun at a low power setting that generates low-amplitude SWs.
      MATERIALS AND METHODS: * Anaesthetised female pigs were assigned to one of three
      SWL treatment protocols that did not involve a pause in SW delivery of >10 s
      (2000 SWs at 24 kV; 100 SWs at 12 kV + ~ 10-s pause + 2000 SWs at 24 kV; 500 SWs
      at 12 kV + ~ 10-s pause + 2000 SWs at 24 kV). * All SWs were delivered at 120
      SWs/min using an unmodified Dornier HM3 lithotripter. * Renal function was
      measured before and after SWL. * The kidneys were then processed for
      quantification of the SWL-induced haemorrhagic lesion. Values for lesion size
      were compared to previous data collected from pigs in which treatment included a
      3-min pause in SW delivery. RESULTS: * All SWL treatment protocols produced a
      similar degree of vasoconstriction (23-41% reduction in glomerular filtration
      rate and effective renal plasma flow) in the SW-treated kidney. * The mean renal
      lesion in pigs treated with 100 low-amplitude SWs delivered before the main dose
      of 2000 high-amplitude SWs (2.27% functional renal volume [FRV]) was
      statistically similar to that measured for pigs treated with 2000 SWs all at high
      amplitude (3.29% FRV). * However, pigs treated with 500 low-amplitude SWs before
      the main SW dose had a significantly smaller lesion (0.44% FRV) that was
      comparable with the lesion in pigs from a previous study in which there was a 3
      min pause in treatment separating a smaller initial dose of 100 low-amplitude SWs
      from the main dose of 2000 high-amplitude SWs (0.46% FRV). The time between the
      initiation of the low - and high-amplitude SWs was ~ 4 min for these latter two
      groups compared with ~ 1 min when there was negligible pause after the initial
      100 low-amplitude SWs in the protocol. CONCLUSIONS: * Pig kidneys treated by SWL
      using a two-step low-to-high power ramping protocol were protected from injury
      with negligible pause between steps, provided the time between the initiation of
      low-amplitude SWs and switching to high-amplitude SWs was ~ 4 min. * Comparison
      with results from previous studies shows that protection can be achieved using
      various step-wise treatment scenarios in which either the initial dose of SWs is
      delivered at low-amplitude for ~ 4 min, or there is a definitive pause before
      resuming SW treatment at higher amplitude. * Thus, we conclude that renal
      protection can be achieved without instituting a pause in SWL treatment. It
      remains prudent to consider that renal protection depends on the acoustic and
      temporal properties of SWs administered at the beginning stages of a SWL ramping
      protocol, and that this may differ according to the lithotripter being used.

PMID- 22612391
TI  - Dihydroergotamine (DHE) use during gestation and the risk of adverse pregnancy
      outcomes.
AB  - BACKGROUND: Dihydroergotamine (DHE) is perceived to be associated with a higher
      risk of adverse pregnancy events, but it has significantly less vasoconstrictive
      and uterotonic effects compared with ergotamine, and has demonstrated no
      teratogenic effect in animals. The objectives of this study were to quantify the
      risk of major congenital malformations (MCMs), prematurity, low birth weight
      (LBW), and spontaneous abortions (SAs) associated with gestational use of DHE,
      triptans, and nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: Four
      independent case-control analyses were conducted within the Quebec Pregnancy
      Registry: (1) MCM; (2) prematurity (<37 weeks of gestation); (3) LBW (birth
      weight <2500 g); (4) clinically detected SA. Exposure was defined dichotomously
      as use of DHE, triptan, and NSAIDs during pregnancy. RESULTS: Overall, 59,707
      pregnant women met the eligibility criteria and were considered (53 [0.08%] used
      DHE, 139 [0.23%] triptans, and 2990 [5.01%] NSAIDs). Adjusting for potential
      confounders, gestational use of DHE was not significantly associated with the
      risk of MCM (odds ratio [OR]: 0.97; 95% confidence interval [CI]: 0.22-4.28), LBW
      (OR: 1.41; 95%CI: 0.25-7.80), or SA (OR: 1.97; 95% CI: 0.21-18.57). DHE use was,
      however, increasing the risk of prematurity (OR: 4.18; 95% CI: 1.34-12.99). In
      users of triptans, the OR for MCM was 1.49 (95% CI: 0.89-2.52), prematurity 0.76
      (95% CI: 0.34-1.66), LBW 0.83 (95% CI: 0.31-2.25), and SA 2.65 (95% CI: 1.57
      4.48). In users of NSAIDs, the OR for MCM was 1.20 (95% CI: 1.06-1.36),
      prematurity 1.10 (95% CI: 0.95-1.26), LBW 1.29 (95% CI: 1.08-1.54), and SA 2.97
      (95% CI: 2.63-3.36). CONCLUSIONS: This study showed that other than for
      prematurity, DHE use during pregnancy was similar to that of triptan use and was
      smaller than the risk associated with NSAID use.

PMID- 22612392
TI  - Sucrose-rich feeding during rat pregnancy-lactation and/or after weaning alters
      glucose and lipid metabolism in adult offspring.
AB  - 1. Adverse fetal and early life environments predispose to the development of
      metabolic disorders in adulthood. The present study examined whether offspring of
      normal Wistar dams fed a high-sucrose diet (SRD) developed impaired lipid and
      glucose homeostasis when fed a control diet (CD) after weaning. In addition, we
      investigated whether there were more pronounced derangements in lipid and glucose
      homeostasis when offspring of SRD-fed Wistar were fed an SRD after weaning
      compared with those in offspring of CD-fed dams weaned on an SRD. 2. During
      pregnancy and lactation, female rats were fed either an SRD or CD. After weaning,
      half the male offspring from both groups were fed a CD or SRD, up to 100 days of
      age (CD-CD, CD-SRD, SRD-SRD and SRD-CD groups). 3. Final bodyweight was similar
      between all groups, although offspring of SRD-fed dams had lighter bodyweight at
      birth. Plasma lipid and glucose levels were significantly higher (P < 0.05)
      without changes in insulin levels in the CD-SRD, SRD-SRD and SRD-CD groups
      compared with the CD-CD group. Dyslipidaemia in the CD-SRD and SRD-SRD groups
      resulted from increased secretion of very low-density lipoprotein
      triacylglycerol, as well as decreased triacylglycerol (TAG) clearance that was
      associated with increased liver TAG content (P < 0.05) compared with the CD-CD
      group. The hypertriglyceridaemia observed in the SRD-CD group was mostly
      associated with decreased TAG clearance. Altered glucose and insulin tolerance
      were observed when the SRD was fed during any period of life. 4. These data
      support the hypothesis that early life exposure to SRD is associated with changes
      in lipid and glucose metabolism, leading to an unfavourable profile in adulthood,
      regardless of whether offspring consumed an SRD after weaning.

PMID- 22612393
TI  - Epidermal growth factor receptor signaling pathway involved in progestin
      resistance of human endometrial carcinoma: In a mouse model.
AB  - AIM: The aim of these investigations was to study the role of gefitinib (a
      specific oral epidermal growth factor receptor-tyrosine kinase inhibitor) on
      reversing progestin-resistance in a human endometrial carcinoma xenograft model.
      MATERIAL AND METHODS: To study the effect of gefitinib and epidermal growth
      factor receptor (EGFR) overexpression on tumor progestin resistance, the Ishikawa
      endometrial carcinoma cell line was transfected to stably express a high level of
      EGFR, which resulted in the progestin-resistant Ishikawa-pLWERNL subcell line.
      BALB/c nude mice were injected subcutaneously with the parental Ishikawa cell
      line and the Ishikawa-pLWERNL cell line. Therapy experiments with gefitinib alone
      or in combination with medroxyprogesterone acetate (MPA) were done and samples
      were analyzed for EGFR and progesterone receptor isoform B (PR-B) expression by
      Western blot and immumohistochemistry analyses. Role in blocking EGFR
      autophosphorylation and its downstream signaling pathway and antagonizing
      progestin resistance by gefitinib was investigated by Western blot analysis.
      RESULTS: EGFR expression was higher in progestin-resistant Ishikawa-pLWERNL
      endometrial cancer (EC) xenografts than in progestin-sensitive Ishikawa EC
      xenografts; in contrast, PR-B was higher in Ishikawa xenografts than in Ishikawa
      pLWERNL xenografts. Higher EGFR expression reduced sensitivity to progestin and
      decreased PR-B expression in Ishikawa xenografts; it also abnormally activated
      EGFR autophosphorylation and its downstream signaling pathway. Gefitinib
      effectively inhibited the proliferation of EC xenografts that overexpressed EGFR,
      and reversed hormone resistance in progestin-resistant EC xenografts. DISCUSSION:
      The present study describes an in vivo model that can provide a valuable tool in
      studying the interaction of overexpressed EGFR and progestin resistance in EC.
      Gefitinib may be useful in the treatment of progestin-resistant EC.

PMID- 22612394
TI  - Localized secondary erythromelalgia in an 11-year-old boy.
AB  - We report an 11-year-old boy with localized secondary erythromelalgia on his left
      medial thigh. The episodes responded well to indomethacin and prednisone but
      recurred after the medications were stopped. The disease was stable after being
      treated for 5 months.

PMID- 22612395
TI  - Zn(2+)-ligation DNAzyme-driven enzymatic and nonenzymatic cascades for the
      amplified detection of DNA.
AB  - A generic fluorescence sensing platform for analyzing DNA by the Zn(2+)-dependent
      ligation DNAzyme as amplifying biocatalyst is presented. The platform is based on
      the target DNA induced ligation of two substrate subunits and the subsequent
      opening of a beacon hairpin probe by the ligated product. The strand displacement
      of the ligated product by the beacon hairpin is, however, of limited efficiency.
      Two strategies are implemented to overcome this limitation. By one method, a
      "helper" nucleic acid sequence is introduced into the system, and this hybridizes
      with the DNAzyme components and releases the ligated product for opening of the
      hairpin. By the second method, a nicking enzyme (Nt.BspQI) is added to the
      system, and this nicks the duplex between the beacon and ligated product while
      recycling the free ligation product. By combining the two coadded components
      ("helper" sequence and nicking enzyme), the sensitive detection of the analyte is
      demonstrated (detection limit, 20 pM). The enzyme-free amplified fluorescence
      detection of the target DNA is further presented by the Zn(2+)-dependent ligation
      DNAzyme-driven activation of the Mg(2+)-dependent DNAzyme. According to this
      method, the Mg(2+)-dependent DNAzyme subunits displace the ligated product, and
      the resulting assembled DNAzyme cleaves a fluorophore/quencher-modified substrate
      to yield fluorescence. The method enabled the detection of the target DNA with a
      detection limit corresponding to 10 pM. The different sensing platforms are
      implemented to detect the Tay-Sachs genetic disorder mutant.

PMID- 22612396
TI  - Controlled synthesis of carbon-coated cobalt sulfide nanostructures in oil phase
      with enhanced li storage performances.
AB  - A novel solvothermal process was developed for the synthesis of carbon-coated
      Co9S8 nanodandelions using 1-dodecanethiol as the sulfur source and the soft
      template. Replacing 1-dodecanethiol with sulfur powder as the sulfur source leads
      to the formation of 20 nm Co9S8 nanoparticles without carbon coating. When tested
      as LIB anode, the C@Co9S8 dandelion delivers a specific capacity of 520 mA h g(
      1) at a current density of 1 A g(-1) (1.8 C) during the 50th cycle, which is much
      higher than that of Co9S8 nanoparticles (e.g. 338 mA h g(-1)). Furthermore, the
      C@Co9S8 dandelion also exhibits excellent high C-rate performance, e.g., depicts
      a 10th-cycle capacity of 373 mA h g(-1) at a current density of 6 A g(-1) (10.9
      C), which is better than that of many reported anode materials. Such synthesis
      approach is attractive for the preparation of sulfide anode materials with high
      Li storage properties. 

PMID- 22612399
TI  - Applicability of a new cell culture device for cooled-storage of stallion semen.
AB  - A new device for storage and shipping of cell cultures--the Petaka G3 cell
      management device--was tested for its applicability for cooled-storage of equine
      semen. Semen from three stallions was processed with EquiPro extender either
      without antibiotics (three ejaculates per stallion) or with gentamicin (250 mg/l;
      three ejaculates per stallion). Semen was either stored at five (anaerobic
      conditions) or 15  degrees C (aerobic conditions) in syringes or cell culture
      devices. Total and progressive motility, as well as membrane integrity of
      spermatozoa, were evaluated from days 1 to 7 after collection with computer
      assisted semen analysis. In experiment 1 (extender without antibiotics), total
      motility, progressive motility and viability of spermatozoa significantly
      decreased over time (p < 0.05). The decrease was significantly faster at 15 
      degrees C than at 5  degrees C (p < 0.05). In the presence of gentamicin
      (experiment 2), this difference was no longer present. It can be concluded that
      cooled-storage of equine semen in sophisticated devices for cell culture is not
      advantageous to syringes for successful maintenance of semen longevity.

PMID- 22612397
TI  - The feasibility of QR-code prescription in Taiwan.
AB  - WHAT IS KNOWN AND OBJECTIVE: An ideal Health Care Service is a service system
      that focuses on patients. Patients in Taiwan have the freedom to fill their
      prescriptions at any pharmacies contracted with National Health Insurance. Each
      of these pharmacies uses its own computer system. So far, there are at least ten
      different systems on the market in Taiwan. To transmit the prescription
      information from the hospital to the pharmacy accurately and efficiently presents
      a great issue. METHODS: This study consisted of two-dimensional applications
      using a QR-code to capture Patient's identification and prescription information
      from the hospitals as well as using a webcam to read the QR-code and transfer all
      data to the pharmacy computer system. Two hospitals and 85 community pharmacies
      participated in the study. RESULTS AND DISCUSSION: During the trial, all
      participant pharmacies appraised highly of the accurate transmission of the
      prescription information. The contents in QR-code prescriptions from Taipei area
      were picked up efficiently and accurately in pharmacies at Taichung area (middle
      Taiwan) without software system limit and area limitation. The QR-code device
      received a patent (No. M376844, March 2010) from Intellectual Property Office
      Ministry of Economic Affair, China. WHAT IS NEW AND CONCLUSION: Our trial has
      proven that QR-code prescription can provide community pharmacists an efficient,
      accurate and inexpensive device to digitalize the prescription contents.
      Consequently, pharmacists can offer better quality of pharmacy service to
      patients.

PMID- 22612401
TI  - Paradoxical gas embolism after SCUBA diving: hemodynamic changes studied by
      echocardiography.
AB  - Hemodynamic changes induced by self-contained underwater breathing apparatus
      diving were investigated using Doppler echocardiography. We detected circulating
      bubbles in both right and left cavities of the heart and in the cerebral
      circulation in two divers with a large patent foramen ovale. A reduction in the
      left ventricular preload was suggested by echocardiographic measurements. The
      decreased cardiac preload was paralleled to a lower stroke volume and cardiac
      output. These findings were also observed in divers with no evidence of
      circulating bubbles. In these subjects, pulmonary vascular resistances remained
      unchanged while an increase was observed in the two divers with arterial bubbles.
      This increase could promote right-to-left shunting. 

PMID- 22612400
TI  - Solid-phase synthesis of lysobactin (katanosin B): insights into structure and
      function.
AB  - The solid phase synthesis of the cyclic depsipeptide antibiotic lysobactin is
      described. The natural product was synthesized via a linear approach using mostly
      an Fmoc-strategy solid phase peptide synthesis (SPPS) with a single purification.
      A lysobactin analog has also been synthesized displaying nanomolar membrane
      disruption activity not seen with the natural product.

PMID- 22612402
TI  - Silver nanovoid arrays for surface-enhanced Raman scattering.
AB  - Highly ordered silver nanovoid arrays are fabricated on porous anodic alumina
      membranes to produce robust and cost-efficient surface-enhanced Raman scattering
      (SERS) substrates. Plasmonic tunability can be accomplished by adjusting the
      topography with different anode voltages. Evenly distributed plasmonic fields,
      high average enhancement factor, and excellent ambient stability due to the
      natural protective layer are some of the unique advantages, and the silver
      nanovoid arrays are applicable to sensing devices.

PMID- 22612403
TI  - A review of expression profiling of circulating microRNAs in men with prostate
      cancer.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that are involved in gene regulation
      and expression. These molecules have been implicated in the pathogenesis of
      several malignancies. MiRNAs have the potential to be both a tissue- and blood
      based biomarker for cancer diagnosis, classification, prognosis and response to
      treatment. The levels of dysregulated miRNAs in the circulation of individuals
      make miRNAs an ideal biomarker for the detection of prostate cancer. The present
      study provides a comprehensive review of the expression profiling of miRNAs in
      the circulation of men with prostate cancer. Further research is necessary to
      identify if circulating miRNAs have the potential to be a biomarker for prostate
      cancer in clinical practice.

PMID- 22612404
TI  - Associations between factors affecting access to care and health-related quality
      of life: results of a statewide HIV/AIDS cross-sectional study.
AB  - The objective of this cross-sectional study was to describe the relationship
      between access to care and health-related quality of life (HRQOL) for persons
      living with HIV/AIDS (PLWHA) in Mississippi by administering a statewide survey.
      A random probability sample of PLWHA was derived from the Mississippi State
      Department of Health's communicable disease tracking system. Interviews were
      conducted with 220 PLWHA to collect data on access to care, demographic and
      social characteristics, and HRQOL. Overall, most participants had access to care
      and reasonable HRQOL. Multivariate and univariate analyses were performed to
      measure associations between access to care and HRQOL. Univariate analyses showed
      that age, income, social networks, severity of disease, having been prescribed
      medications, and having experienced problems accessing care to be significantly
      associated with HRQOL scales. Multivariate analysis of variance models further
      demonstrated low-income level, having experienced problems accessing care, and
      having been prescribed antiretroviral medications to be significantly associated
      with HRQOL. Reducing barriers is a major factor in improving quality of life.
      This study provides needed insight into the relationship between access to care
      and HRQOL among PLWHA in Mississippi, which could be valuable to public health
      planners to help them better understand how to make the greatest impact on HRQOL.

PMID- 22612406
TI  - Explaining variation in perceived team effectiveness: results from eleven quality
      improvement collaboratives.
AB  - AIMS AND OBJECTIVES: Explore effectiveness of 11 collaboratives focusing on 11
      different topics, as perceived by local improvement teams and to explore
      associations with collaborative-, organisational- and team-level factors.
      BACKGROUND: Evidence underlying the effectiveness of quality improvement
      collaboratives is inconclusive and few studies investigated determinants of
      implementation success. Moreover, most evaluation studies on quality improvement
      collaboratives are based on one specific topic or quality problem, making it hard
      to compare across collaboratives addressing different topics. DESIGN: A multiple
      case cross-sectional study. METHODS: Quality improvement teams in 11 quality
      improvement collaboratives focusing on 11 different topics. Team members received
      a postal questionnaire at the end of each collaborative. Of the 283 improvement
      teams, 151 project leaders and 362 team members returned the questionnaire.
      RESULTS: Analysis of variance revealed that teams varied widely on perceived
      effectiveness. Especially, members in the Prevention of Malnutrition and
      Prevention of Medication Errors collaboratives perceived a higher effectiveness
      than other groups. Multilevel regression analyses showed that educational level
      of professionals, innovation attributes, organisational support, innovative
      culture and commitment to change were all significant predictors of perceived
      effectiveness. In total, 27.9% of the individual-level variance, 57.6% of the
      team-level variance and 80% of the collaborative-level variance could be
      explained. CONCLUSION: The innovation's attributes, organisational support, an
      innovative team culture and professionals' commitment to change are instrumental
      to perceived effectiveness. The results support the notion that a layered
      approach is necessary to achieve improvements in quality of care and provides
      further insight in the determinants of success of quality improvement
      collaboratives. RELEVANCE TO CLINICAL PRACTICE: Understanding which factors
      enhance the impact of quality improvement initiatives can help professionals to
      achieve breakthrough improvement in care delivery to patients on a wide variety
      of quality problems.

PMID- 22612405
TI  - Levels of Selenomonas species in generalized aggressive periodontitis.
AB  - BACKGROUND AND OBJECTIVE: To compare the levels of Selenomonas sputigena and
      uncultivated/unrecognized Selenomonas species in subgingival biofilms from
      periodontally healthy subjects and from subjects with generalized aggressive
      periodontitis. MATERIAL AND METHODS: Fifteen periodontally healthy subjects and
      15 subjects with generalized aggressive periodontitis were recruited and their
      clinical periodontal parameters were evaluated. Nine subgingival plaque samples
      were collected from each subject and all were individually analyzed for the
      levels of 10 bacterial taxa, including cultured and uncultivated/unrecognized
      microorganisms, using the RNA-oligonucleotide quantification technique. Between
      group differences in the levels of the test taxa were determined using the Mann
      Whitney U-test. RESULTS:   Subjects with generalized aggressive periodontitis
      showed significantly higher mean counts of Porphyromonas gingivalis, S. sputigena
      and the Mitsuokella sp. Human Oral Taxon (HOT) 131 (previously described as
      Selenomonas sp. oral clone CS002), while higher mean counts of Actinomyces
      gerencseriae and Streptococcus sanguinis were found in periodontally healthy
      subjects (p < 0.01). Selenomonas sp. HOT 146 was only detected in the generalized
      aggressive periodontitis group. In the generalized aggressive periodontitis
      group, the levels of P. gingivalis and S. sputigena were higher in deep sites
      (probing depth >= 5 mm) than in shallow sites (probing depth <= 3 mm) (p < 0.01).
      Furthermore, in subjects with generalized aggressive periodontitis, sites with
      probing depth of <= 3 mm harbored higher levels of these two species than sites
      with the same probing depth in periodontally healthy subjects. There were
      positive correlations between probing depth and the levels of P. gingivalis (r =
      0.77; p < 0.01), S. sputigena (r = 0.60; p < 0.01) and Selenomonas dianae
      (previously described as Selenomonas sp. oral clone EW076) (r = 0.42, p < 0.05).
      CONCLUSION: S. sputigena and Mitsuokella sp. HOT 131 may be associated with the
      pathogenesis of generalized aggressive periodontitis, and their role in the onset
      and progression of this infection should be investigated further.

PMID- 22612408
TI  - Correlates of fatigue phenomenon in palliative care patients with advance cancers
      in Taiwan.
AB  - BACKGROUND: Fatigue is a multidimensional phenomenon that has different meanings
      according to different societal and cultural settings. This study aims to
      decipher fatigue in Taiwanese patients with cancer. METHODS: We recruited 440
      patients with advanced cancer admitted consecutively to the palliative care unit
      of a major medical center in Taiwan. The data were collected at admission, 1 and
      2 weeks after admission, and 2 days before death. RESULTS: The subject group
      consisted of 51.8% males and 48.2% females with a median age of 67 years (ranging
      from 27 to 93 years). The leading primary tumor sites among these patients were
      lung (20.2%), liver (18.0%), and colon-rectum (10.7%), and the median survival
      was 15 days, with a range of 1 to 418 days. All symptoms improved 1 week after
      admission, but most of them significantly worsened 2 days before death. In
      general, the physical signs manifested variation patterns similar to those of
      symptoms. The severity of psychosocial distress and death fear was lower after
      admission and retained the same level at 2 days before death, defying the
      consistent patterns found in other symptoms and signs. In the correlation
      analysis, most symptoms were correlated with fatigue during admission, with
      weakness being the most significant one. Although self-efficacy and emotion were
      correlated with fatigue both on admission and 1 week after admission, social
      support and death fear were not correlated with fatigue at all times. CONCLUSION:
      The meaning of fatigue is mainly associated with physical factors among these
      patients. Education of complexities in fatigue in tandem with psychosocial and
      spiritual care may help alleviate this symptom, and promote quality of life.

PMID- 22612407
TI  - Cancer family caregivers: a new direction for interventions.
AB  - BACKGROUND: Descriptive studies of cancer family caregivers demonstrate role
      related psychosocial and physical burden; however, little is known about which
      factors contribute to or obviate burden. Systematic reviews of caregiver
      intervention studies demonstrate mixed results, perhaps because some caregiver
      needs are still unknown and not adequately addressed. The purpose of our study
      was to explore the lived experience of being a caregiver for an adult with lung
      or colon cancer, so as to guide the development of future intervention studies.
      METHOD: Using phenomenologic methods, open-ended interviews were conducted at a
      chemotherapy clinic, New Haven, CT with 135 caregivers to adults with lung or
      colon cancer. Interviews were audio-recorded and transcribed. Thematic analysis
      was conducted with transcripts coded, reviewed, and recoded multiple times. The
      final 69 codes were reduced to 13 code clusters (thematic categories) distributed
      among 4 themes. RESULTS: Four inter-related themes emerged: 1) becoming a
      caregiver; 2) new and altered relationships; 3) personal responses to caregiving
      and 4) antecedents and social context. Caregivers describe hearing the cancer
      diagnosis as "life-changing". The cancer creates the context for the caregiver's
      relationships (with the patient, self, others, and the healthcare system), and
      cognitive, behavioral, affective, and spiritual responses. The caregiver's
      antecedent experiences and social support network form the foundation for their
      perceptions of the diagnosis, relationships, and personal responses. CONCLUSION:
      This study implicates several intervention components to be developed and tested
      as favorably supporting caregivers, namely, reinforcing positive aspects of
      caregiving, cultivating open communication, and acknowledging the prior
      experiences and social foundation of the caregiver's life that can be supportive
      or burdensome.

PMID- 22612410
TI  - Bioassay-directed isolation and identification of phytotoxic and fungitoxic
      acetylenes from Conyza canadensis.
AB  - Conyza canadensis (L.) Cronquist syn. (horseweed) is a problematic and invasive
      weed with reported allelopathic properties. To identify the phytotoxic
      constituents of the aerial parts, a systematic bioactivity-guided fractionation
      of the dichloromethane extract was performed. Three active enyne derivatives,
      (2Z,8Z)-matricaria acid methyl ester, (4Z,8Z)-matricaria lactone, and (4Z)
      lachnophyllum lactone, were identified. The lactones inhibited growth of the
      monocot Agrostis stolonifera (bentgrass) and the dicot Lactuca sativa (lettuce)
      at 1 mg mL(-1), while the (2Z,8Z)-matricaria acid methyl ester was less active.
      In a dose-response screening of the lactones for growth inhibitory activity
      against Lemna paucicostata , (4Z)-lachnophyllum lactone was the most active with
      an IC50 of 104 MUM, while the (4Z,8Z)-matricaria lactone was less active (IC50 of
      220 MUM). In a fungal direct bioautography assay, the two lactones at 10 and 100
      MUg/spot inhibited growth of the plant pathogenic fungi Colletotrichum acutatum ,
      Colletotrichum fragariae , and Colletotrichum gloeosporioides . In a dose
      response screening of the lactones against six different plant pathogenic fungi,
      (4Z,8Z)-matricaria lactone was more active than the commercial fungicide
      azoxystrobin on Col. acutatum , Col. fragariae , and Col. gloeosporioides at 30
      MUM and about as active as the commercial fungicide captan against Col.
      gloeosporioides , while (4Z)-lachnophyllum lactone was less active. 

PMID- 22612411
TI  - Novel real-time feedback and integrated simulation model for teaching and
      evaluating ultrasound-guided regional anesthesia skills in pediatric anesthesia
      trainees.
AB  - OBJECTIVES: To assess, teach, and improve core competencies and skills sets
      associated with ultrasound-guided regional anesthesia (UGRA) of pediatric
      anesthesia trainees. AIM: To effectively assess and improve UGRA-associated
      cognitive and technical skills and proficiency of pediatric anesthesia trainees
      using simulators and real-time feedback. BACKGROUND: Ultrasound usage has been
      increasingly adopted by anesthesiologists to perform regional anesthesia.
      Pediatric UGRA performance significantly lags behind adult UGRA practice. Lack of
      effective UGRA training is the major reason for this unfortunate lag. Integration
      of ultrasound imaging, target location, and needling skills are crucial in safely
      performing UGRA. However, there are no standards to ensure proficiency in
      practice, nor in training. METHODS: We implemented an UGRA instructional program
      for all trainees, in two parts. First, we used a unique training model for
      initial assessment and training of technical skills. Second, we used an
      instructional program that encompasses UGRA and equipment-associated cognitive
      skills. After baseline assessment at 0 months, we retested these trainees at 6
      and 12 months to identify progression of proficiency over time. RESULTS:
      Cognitive and technical UGRA skills of trainees improved significantly over the
      course of time. UGRA performance average accuracy improved to 79% at 12 months
      from the baseline accuracy of 57%. Cognitive UGRA-related skills of trainees
      improved from baseline results of 52.5-79.2% at 12 months. CONCLUSIONS:
      Implementing a multifaceted assessment and real-time feedback-based training has
      significantly improved UGRA-related cognitive and technical skills and
      proficiency of pediatric anesthesia trainees.

PMID- 22612412
TI  - Increased sensitivity in proton transfer reaction mass spectrometry by
      incorporation of a radio frequency ion funnel.
AB  - A drift tube capable of simultaneously functioning as an ion funnel is
      demonstrated in proton transfer reaction mass spectrometry (PTR-MS) for the first
      time. The ion funnel enables a much higher proportion of ions to exit the drift
      tube and enter the mass spectrometer than would otherwise be the case. An
      increase in the detection sensitivity for volatile organic compounds of between 1
      and 2 orders of magnitude is delivered, as demonstrated using several compounds.
      Other aspects of analytical performance explored in this study include the
      effective E/N (ratio of electric field to number density of the gas) and dynamic
      range over which the drift tube is operated. The dual-purpose drift tube/ion
      funnel can be coupled to various types of mass spectrometers to increase the
      detection sensitivity and may therefore offer considerable benefits in PTR-MS
      work.

PMID- 22612409
TI  - The hypothalamic-pituitary-adrenal axis and sex hormones in chronic stress and
      obesity: pathophysiological and clinical aspects.
AB  - Obesity, particularly the abdominal phenotype, has been ascribed to an individual
      maladaptation to chronic environmental stress exposure mediated by a
      dysregulation of related neuroendocrine axes. Alterations in the control and
      action of the hypothalamic-pituitary-adrenal axis play a major role in this
      context, with the participation of the sympathetic nervous system. The ability to
      adapt to chronic stress may differ according to sex, with specific
      pathophysiological events leading to the development of stress-related chronic
      diseases. This seems to be influenced by the regulatory effects of sex hormones,
      particularly androgens. Stress may also disrupt the control of feeding, with some
      differences according to sex. Finally, the amount of experimental data in both
      animals and humans may help to shed more light on specific phenotypes of obesity,
      strictly related to the chronic exposure to stress. This challenge may
      potentially imply a different pathophysiological perspective and, possibly, a
      specific treatment.

PMID- 22612414
TI  - Severe group a streptococcus surgical site infection after thyroid lobectomy.
AB  - BACKGROUND: Thyroidectomy is rarely complicated by a surgical site infection
      (SSI). Despite its low incidence, post-thyroidectomy SSI is especially concerning
      because of its proximity to vital head and neck structures and the very real
      potential for airway compromise and death. Severe SSIs frequently are caused by
      Group A Streptococcus (GAS) because of its potential for developing into
      necrotizing fascitis. No description of the surgical approach to a necrotizing
      soft-tissue infection after thyroid resection is available in the current
      literature. METHODS: Case report and review of the pertinent English-language
      literature. RESULTS: A 47-year-old male underwent a right thyroid lobectomy and
      isthmusectomy for a follicular neoplasm. On post-operative day 2, the patient
      presented to the emergency department with persistent pain, rapid onset of
      swelling, and airway compromise shown on computed tomography scan. Emergency
      incision and drainage revealed a severe soft tissue infection. Because of
      subsequent worsening erythema and soft-tissue swelling, the patient had to be re
      explored. The infection, later identified as caused by GAS, might have been
      transmitted from the patient's daughter. CONCLUSION: To our knowledge, this is
      the first case reported of exposure to a family member with GAS pharyngitis.
      Successful treatment requires an appropriately high level of suspicion followed
      by emergent operative debridement and systemic antibiotics.

PMID- 22612413
TI  - Frequency and genetic characterization of V(DD)J recombinants in the human
      peripheral blood antibody repertoire.
AB  - Antibody heavy-chain recombination that results in the incorporation of multiple
      diversity (D) genes, although uncommon, contributes substantially to the
      diversity of the human antibody repertoire. Such recombination allows the
      generation of heavy chain complementarity determining region 3 (HCDR3) regions of
      extreme length and enables junctional regions that, because of the nucleotide
      bias of N-addition regions, are difficult to produce through normal V(D)J
      recombination. Although this non-classical recombination process has been
      observed infrequently, comprehensive analysis of the frequency and genetic
      characteristics of such events in the human peripheral blood antibody repertoire
      has not been possible because of the rarity of such recombinants and the
      limitations of traditional sequencing technologies. Here, through the use of high
      throughput sequencing of the normal human peripheral blood antibody repertoire,
      we analysed the frequency and genetic characteristics of V(DD)J recombinants. We
      found that these recombinations were present in approximately 1 in 800
      circulating B cells, and that the frequency was severely reduced in memory cell
      subsets. We also found that V(DD)J recombination can occur across the spectrum of
      diversity genes, indicating that virtually all recombination signal sequences
      that flank diversity genes are amenable to V(DD)J recombination. Finally, we
      observed a repertoire bias in the diversity gene repertoire at the upstream (5')
      position, and discovered that this bias was primarily attributable to the order
      of diversity genes in the genomic locus.

PMID- 22612415
TI  - Is missing maxillary lateral incisor in complete cleft lip and palate a product
      of genetics or local environment?
AB  - OBJECTIVE: To test the null hypothesis: Subjects with isolated complete
      unilateral cleft lip and palate (UCLP) show no differences in overall frequency
      of tooth agenesis (hypodontia), comparing a subsample with cleft-side maxillary
      lateral incisor (MxI2) agenesis to a subsample without cleft-side MxI2 agenesis.
      Findings could clarify the origins of cleft-side MxI2 agenesis. MATERIALS AND
      METHODS: Tooth agenesis was identified from dental radiographs of 141 subjects
      with UCLP. The UCLP cohort was segregated into four categories according to the
      status and location of MxI2 in the region of the unilateral cleft: group M:
      subjects with one tooth, located on the mesial side of the alveolar cleft; group
      D: subjects with one tooth, located on the distal side of the alveolar cleft;
      group MD: subjects with two teeth present, one mesial and one distal to the
      cleft; and group ABS: subjects with lateral incisor absent (agenesis) in the
      cleft area. RESULTS: The null hypothesis was rejected. Among UCLP subjects, there
      was a twofold increase (P < .0008) in overall frequency of tooth agenesis outside
      the cleft region in a subsample with cleft-side MxI2 agenesis (ABS), compared to
      a subsample presenting with no agenesis of the cleft-side MxI2 (M+D+MD).
      CONCLUSIONS: Cleft-side MxI2 agenesis in CLP subjects appears to be largely a
      genetically controlled anomaly associated with cleft development, rather than a
      collateral environmental consequence of the adjacent cleft defect, since
      increased hypodontia involving multiple missing teeth observed remote from a
      cleft clearly has a significant genetic basis.

PMID- 22612417
TI  - The effect of solvent additives on morphology and excited-state dynamics in
      PCPDTBT:PCBM photovoltaic blends.
AB  - The dependence of the thin film morphology and excited-state dynamics for the low
      bandgap donor-acceptor copolymer poly[2,6-(4,4-bis-(2-ethylhexyl)-4H
      cyclopenta[2,1-b;3,4-b']-dithiophene)-alt-4,7-(2,1,3-benzothiadiazole)] (PCPDTBT)
      in pristine films and in blends (1:2) with [6,6]-phenyl-C(61)-butyric acid methyl
      ester (PCBM) on the use of the solvent additive 1,8-octanedithiol (ODT) is
      studied by solid-state nuclear magnetic resonance (NMR) spectroscopy and
      broadband visible and near-infrared pump-probe transient absorption spectroscopy
      (TAS) covering a spectral range from 500-2000 nm. The latter allows monitoring of
      the dynamics of excitons, bound interfacial charge-transfer (CT) states, and free
      charge carriers over a time range from femto- to microseconds. The broadband pump
      probe experiments reveal that excitons are not only generated in the polymer but
      also in PCBM-rich domains. Depending on the morphology controlled by the use of
      solvent additives, polymer excitons undergo mainly ultrafast dissociation (<100
      fs) in blends prepared without ODT or diffusion-limited dissociation in samples
      prepared with ODT. Excitons generated in PCBM diffuse slowly to the interface in
      both samples and undergo dissociation on a time scale of several tens of
      picoseconds up to hundreds of picoseconds. In both samples a significant fraction
      of the excitons creates strongly bound interfacial CT states, which exhibit
      subnanosecond geminate recombination. The total internal quantum efficiency loss
      due to geminate recombination is estimated to be 50% in samples prepared without
      ODT and is found to be reduced to 30% with ODT, indicating that more free charges
      are generated in samples prepared with solvent additives. In samples prepared
      with ODT, the free charges exhibit clear intensity-dependent recombination
      dynamics, which can be modeled by Langevin-type recombination with a bimolecular
      recombination coefficient of 6.3 * 10(-11) cm(3) s(-1). In samples prepared
      without ODT, an additional nanosecond recombination of polaron pairs is observed
      in conjunction with an increased intensity-independent trap-assisted nongeminate
      recombination of charges. Furthermore, a comparison of the triplet-induced
      absorption spectra of PCPDTBT with the charge-induced absorption in PCPDTBT:PCBM
      blends reveals that triplets have a very similar excited-state absorption
      spectrum compared to the free charge carriers, however, in contrast have a
      distinct intensity-independent lifetime. Overall, our results suggest that
      whether free charges or strongly bound CT states are created upon dissociation of
      excitons at the PCPDTBT:PCBM interface is determined instantaneously upon exciton
      dissociation and that once formed strongly bound CT states rapidly recombine and
      thus are unlikely to dissociate into free charges. The observation of a
      significantly larger bimolecular recombination coefficient than previously
      determined for poly(3-hexylthiophen-2,5-diyl):PCBM (P3HT:PCBM) and PCDTBT:PCBM
      samples indicates that nongeminate recombination of free charges considerably
      competes with charge extraction in PCPDTBT:PCBM photovoltaic devices.

PMID- 22612416
TI  - The oligopeptide DT-2 is a specific PKG I inhibitor only in vitro, not in living
      cells.
AB  - BACKGROUND AND PURPOSE: cGMP is involved in the regulation of many cellular
      processes including cardiac and smooth muscle contractility, aldosterone
      synthesis and inhibition of platelet activation. Intracellular effects cGMP are
      mediated by cGMP-dependent PKs, cGMP-regulated PDEs and cGMP-gated ion channels.
      PKG inhibitors are widely used to discriminate PKG-specific effects. They can be
      divided into cyclic nucleotide-binding site inhibitors such as Rp
      phosphorothioate analogues (Rp-cGMPS), ATP-binding site inhibitors such as
      KT5823, and substrate binding site inhibitors represented by the recently
      described DT-oligopeptides. As it has been shown that Rp-cGMPS and KT5823 have
      numerous non-specific effects, we analysed the pharmacological properties of the
      oligopeptide (D)-DT-2 described as a highly specific, membrane-permeable, PKG
      inhibitor. EXPERIMENTAL APPROACH: Specificity and potency of (D)-DT-2 to inhibit
      PKG activity was evaluated using biochemical assays in vitro and by substrate
      phosphorylation analysis in various cell types including human platelets, rat
      mesangial cells and rat neonatal cardiomyocytes. KEY RESULTS: Despite potent
      inhibition of PKGI in vitro, (D)-DT-2 lost specificity for PKG in cell
      homogenates and particularly in living cells, as demonstrated by phosphorylation
      of different substrates. Instead, (D)-DT-2 modulated activity of other kinases
      including ERK, p38, PKB and PKC, thereby inducing unpredicted and often opposing
      functional effects. CONCLUSIONS AND IMPLICATIONS: We conclude that DT
      oligopeptides, as other inhibitors, cannot be used to specifically inhibit PKG in
      intact cells. Therefore, no specific pharmacological PKG inhibitors are
      available, and reliable studies of PKG signalling can only be made by using RNA
      knockdown or genetic deletion methods.

PMID- 22612418
TI  - FT23, an orally active antifibrotic compound, attenuates structural and
      functional abnormalities in an experimental model of diabetic cardiomyopathy.
AB  - Diabetic cardiomyopathy is characterized by early diastolic dysfunction and
      structural changes, such as interstitial fibrosis and cardiac hypertrophy. Using
      the Ren-2 rat model, we sought to investigate the effect of FT23 on the
      structural and functional changes associated with diabetic cardiomyopathy.
      Heterozygous Ren-2 rats were rendered diabetic with streptozotocin by tail vein
      injection. Rats were then treated with FT23 (200 mg/kg per day by gavage twice
      daily) or vehicle from Week 8 to Week 16 after the onset of diabetes.
      Echocardiography was performed to assess heart function before the rats were
      killed and their hearts collected for histological and molecular biological
      assessment. The antifibrotic effect of FT23 was compared with that of tranilast
      in neonatal cardiac fibroblasts when stimulated with transforming growth factor
      (TGF)-beta (5 ng/mL) at 30, 50 and 100 umol/L. FT23 exhibited greater inhibition
      of TGF-beta-induced collagen production in neonatal cardiac fibroblasts, as
      measured by a [(3) H]-proline incorporation assay, compared with its parental
      compound tranilast. In the in vivo study, FT23 significantly attenuated the
      increased heart weight : bodyweight ratio in FT23-treated diabetic Ren-2 rats.
      Diastolic dysfunction, as measured by mitral valve (MV) E/A ratio and MV
      deceleration time, was also significantly attenuated by FT23. Picrosirius red
      stained heart sections revealed that cardiac fibrosis in the diabetic rats was
      reduced by FT23 compared with that in vehicle-treated rats, with a concomitant
      reduction in collagen I immunostaining and infiltration of macrophages, as
      demonstrated by ED1 immunostaining. The results of the present study suggest that
      FT23 inhibits the activity of TGF-beta and attenuates structural and functional
      manifestations of diastolic dysfunction observed in a model of diabetic
      cardiomyopathy.

PMID- 22612419
TI  - Serum interleukin-9 levels are associated with clinical severity in children with
      atopic dermatitis.
AB  - Atopic dermatitis (AD) is an inflammatory disorder of the skin characterized by
      impaired immune response. Th9 cells are a sub-population of T cells that release
      interleukin (IL)-9. No study has investigated the role of IL-9 in AD. This study
      compared 64 children with AD with 45 healthy children. Serum IL-9 levels were
      measured and clinical symptoms were assessed. Children with AD had higher serum
      IL-9 levels than controls (p = 0.01). Clinical severity was significantly related
      to IL-9 level, indicating that IL-9 might exert a pathogenic role in symptom
      occurrence in individuals with AD. Children with AD may have higher serum IL-9
      levels than healthy children, and IL-9 levels are significantly related to
      symptom severity.

PMID- 22612420
TI  - Human love--the inner essence of nursing ethics according to Estrid Rodhe. A
      study using the approach of history of ideas.
AB  - The aim of this study is to describe the idea pattern of nursing ethics in the
      textbook written by the Swedish nurse Estrid Rodhe (1911). The purpose is to
      increase understanding of the ideas in early written history of nursing ethics by
      using the method of history of ideas. A theoretical premise, but also a
      fascinating factor in this study, is that the ethics of one profession is always
      contextual in relation to current period. The historical context of Rodhe's time
      was a time of difficult societal circumstances in Europe. Nurses' work was
      demanding, but a distinctive feature was enthusiasm to develop nursing.
      Discussion of the moral issues of nursing was intense, and the characteristics of
      a good nurse consisted of being as altruistic and unselfish woman. Based on our
      analysis, the inner essence of Rodhe's idea pattern consists of human love. It is
      reflected in her ideas of calling-based altruism, virtuous woman as a personal
      reason for being a nurse and nurses' ethical duty to implementation and
      subservience. Rodhe's thinking reflects the conventions of her time. The role of
      personal moral characteristics of nurses was highlighted and not viewed as
      separable from the professional. Her textbook represented nursing knowledge of
      ethics written by a nurse and making her a pioneer of the early written history
      of nursing in general. Understanding the past helps us comprehend current issues
      in nursing and makes visible cultural values that form the basis for today and
      tomorrow. It also provides a possibility to observe the same fundamental features
      in spite of temporal distance. Here, the history of ideas is a beneficial and
      fruitful method to increase our understanding of nursing ethics.

PMID- 22612422
TI  - Plutonium fractionation in southern Baltic Sea sediments.
AB  - In this study, different chemical plutonium fractions (dissolved in water,
      connected to carbonates, connected to oxides, complexed with organic matter,
      mineral acids soluble and the rest) in sediments from the Vistula River estuary,
      the Gdansk Basin and the Bornholm Deep were determined. The distribution of
      (239+240)Pu in analysed sediments samples was not uniform but dependent on its
      chemical form, depth and the sediment geomorphology. The highest amount of
      plutonium exists in middle parts of sediments and comes from the global
      atmospheric fallout from nuclear tests in 1958-1961. According to all analysed
      fractions, the biggest amount of (239+240)Pu was in the mobile form, connected to
      carbonate fractions from the Vistula River estuary, the Gulf of Gdansk and the
      Bornholm Deep sediments.

PMID- 22612423
TI  - Dosing issues in Parkinson's disease--patient preferences and their influence on
      compliance.

PMID- 22612424
TI  - Tyrosine kinase inhibitors as potential drugs for B-cell lymphoid malignancies
      and autoimmune disorders.
AB  - INTRODUCTION: In the last few years, several tyrosine kinase inhibitors (TKIs)
      have been synthesized and become available for preclinical studies and clinical
      trials. This article summarizes recent achievements in the mechanism of action,
      pharmacological properties, and clinical activity and toxicity, as well as the
      emerging role of TKIs in lymphoid malignancies, allergic diseases, and autoimmune
      disorders. AREAS COVERED: A literature review was conducted of the MEDLINE
      database PubMed for articles in English. Publications from 2000 through January
      2012 were scrutinized. The search terms used were Bruton's tyrosine kinase (Btk)
      inhibitors, PCI-32765, GDC-0834, LFM-A13, AVL-101, AVL-292, spleen tyrosine
      kinase (Syk) inhibitors, R343, R406, R112, R788, fostamatinib, BAY-61-3606, C-61,
      piceatannol, Lyn, imatinib, nilotinib, bafetinib, dasatinib, GDC-0834, PP2,
      SU6656 in conjunction with lymphoid malignancy, NHL, CLL, autoimmune disease,
      allergic disease, asthma, and rheumatoid arthritis. Conference proceedings from
      the previous 5 years of the American Society of Hematology, European Hematology
      Association, American Society of Clinical Oncology, and ACR/ARHP Annual
      Scientific Meetings were searched manually. Additional relevant publications were
      obtained by reviewing the references from the chosen articles. EXPERT OPINION:
      The use of TKIs, especially inhibitors of Btk, Syk, and Lyn, is a promising new
      strategy for targeted treatment of B-cell lymphoid malignancies, autoimmune
      disorders and allergic diseases. However, definitive data from ongoing and future
      clinical trials will aid in better defining the status of TKIs in the treatment
      of these disorders.

PMID- 22612425
TI  - Effect of cooling during inter-exercise periods on subsequent intramuscular water
      movement and muscle performance.
AB  - To evaluate the effects of cooling between exercise sessions on intramuscular
      water movement and muscle performance, the lower extremities of nine untrained
      men were assigned to either a cooling protocol (20-min water immersion, 15 
      degrees C) or a noncooling protocol. Each subject performed two exercise sessions
      involving maximal concentric knee extension and flexion (three repetitions, 60
      degrees /s; followed by 50 repetitions, 180 degrees /s). The peak torque at 60
      degrees /s and total work, mean power, and decrease rate of torque value at 180
      degrees /s were evaluated. Axial magnetic resonance diffusion-weighted images of
      the mid-thigh were obtained before and after each exercise session. Apparent
      diffusion coefficient (ADC) values for the quadriceps and hamstrings were
      calculated for evaluating intramuscular water movement. Both groups exhibited
      significantly increased ADC values for the quadriceps and hamstrings after each
      exercise session. These ADC values returned to the pre-exercise level after water
      immersion. No significant difference was observed in muscle performance from
      first exercise session to the next in either group, except for increased total
      work and mean power in knee flexion in the cooled group. Cooling intervention
      between exercise sessions decreased exercise-induced elevation of intramuscular
      water movement and had some beneficial effects on muscle endurance of knee
      flexors, but not knee extensors. 

PMID- 22612427
TI  - Orthostatic hypotension and subjective sleep quality in older people.
AB  - Poor sleep quality and orthostatic hypotension are common complaints in an older
      population, and both are related to factors such as polypharmacy and depression.
      However, it is not known whether there is a direct association between the two.
      Our objective is to investigate a potential association between orthostatic blood
      pressure response and subjective sleep quality in older people. A within
      subjects, cross-sectional design embedded in a larger longitudinal study design.
      Participants were recruited from the community to visit the TRIL clinic at St
      James's Hospital, where they underwent a structured medical and psychosocial
      assessment. A total of 505 community dwelling adults aged 60+ (321 females, mean
      age 72.44) were participated in this study. Orthostatic blood pressure responses
      were recorded during an active stand using Finometer equipment, and health
      related factors such as pain ratings, co-morbidities, polypharmacy, timed up and
      go, Mini-Mental State Examination score, body mass index, as well as depression,
      anxiety, age and gender, were also recorded. Self-reported sleep quality was also
      assessed using the Pittsburgh Sleep Quality Index. The results showed that timed
      up and go, polypharmacy, depression, anxiety, gender and delayed recovery of
      blood pressure at orthostasis were associated with subjective poor sleep quality.
      There is an association between subjective sleep quality and delayed recovery of
      blood pressure at orthostasis, independent of mental health or polypharmacy
      effects, in older adults. This link may have implications for the management of
      sleep disorders in older people.

PMID- 22612428
TI  - Effect of aspect ratio and deformability on nanoparticle extravasation through
      nanopores.
AB  - We describe the fabrication of filamentous hydrogel nanoparticles using a unique
      soft lithography based particle molding process referred to as PRINT (particle
      replication in nonwetting templates). The nanoparticles possess a constant width
      of 80 nm, and we varied their lengths ranging from 180 to 5000 nm. In addition to
      varying the aspect ratio of the particles, the deformability of the particles was
      tuned by varying the cross-link density within the particle matrix. Size
      characteristics such as hydrodynamic diameter and persistence length of the
      particles were analyzed using dynamic light scattering and electron microscopy
      techniques, respectively, while particle deformability was assessed by atomic
      force microscopy. Additionally, the ability of the particles to pass through
      membranes containing 0.2 MUm pores was assessed by means of a simple filtration
      technique, and particle recovery was determined using fluorescence spectroscopy.
      The results show that particle recovery is mostly independent of aspect ratio at
      all cross-linker concentrations utilized, with the exception of 96 wt % PEG
      diacrylate 80 * 5000 nm particles, which showed the lowest percent recovery.

PMID- 22612429
TI  - Rapid shotgun proteomic liquid chromatography-electrospray ionization-tandem mass
      spectrometry-based method for the lupin ( Lupinus albus L.) multi-allergen
      determination in foods.
AB  - Allergy to lupin is a growing food safety problem because this legume,
      increasingly exploited in the food industry, is one of the allergens that,
      according to law, must be declared on the labels of food products in the European
      Union. In this context, a rapid targeted proteomic approach based on liquid
      chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS)
      analysis was proposed and aimed to unequivocal confirmation and reliable
      determination of the major lupin allergens, i.e., conglutins, in pasta and
      biscuits. Detected concentrations were around 1 mg of lupin/kg of pasta and
      biscuits, proving the capabilities of the MS-based method in terms of the
      sensitive allergen screening method. Good precision was observed in terms of both
      intra- and interday repeatability, with relative standard deviation (RSD) lower
      than 23%. Recoveries from 95 +/- 10 to 118 +/- 12% and from 103 +/- 1 to 110 +/-
      12% ranges were calculated for biscuits and pasta, respectively. Finally, the
      applicability of the devised method was investigated by analyzing market samples
      containing lupin and samples that may possibly contain traces of lupin deriving
      from cross-contamination between products and production lines. 

PMID- 22612430
TI  - Phylogeography and species biogeography of montane Great Basin stoneflies.
AB  - Sky islands are ideal systems for determining the effects of climatic
      oscillations on species distributions and genetic structure. Our study focused on
      montane stonefly populations in the Great Basin of western North America. We used
      niche-based distribution modelling, phylogeography and traditional species-based
      biogeography to test several hypotheses as follows: (i) genetic differentiation
      among Doroneuria baumanni populations will be independent of hydrologic
      connectivity (headwater model); (ii) Sky islands were colonized when habitat was
      more continuous and populations likely experienced multiple expansions and
      contractions; (iii) Colonization events were coincident with the late Pleistocene
      and Holocene; and (iv) Shared topography and climate history will result in
      concordant patterns of genetic differentiation in D. baumanni and occurrences of
      32 stonefly species across the region. Overall, Phi(ST) 's and coalescent-based
      estimates of migration were consistent with the headwater model. Maximum
      likelihood and Bayesian gene trees identified three major nonoverlapping east
      west clades. Distribution modelling indicated more suitable habitat in the Great
      Basin during the Last Glacial Maximum than at present, but none during the last
      interglacial period. Demographic analyses showed evidence of population expansion
      in one of the three major east-west clades. Intra-clade divergence times (60,000
      183,000ybp) were well within the late Pleistocene while among-clade divergence
      times (499.000-719,000ybp) were deeper. Genetic differentiation in D. baumanni
      and distributions of stonefly species were significantly concordant. These
      results imply that climatic oscillations have played major roles in shaping the
      genetic structure and distributions of Great Basin stoneflies, but that
      divergence among clades occurred much earlier than our late Pleistocence/early
      Holocene predictions.

PMID- 22612432
TI  - Mother-adolescent conflict as a mediator between adolescent problem behaviors and
      maternal psychological control.
AB  - This study examined mother-adolescent conflict as a mediator of longitudinal
      reciprocal relations between adolescent aggression and depressive symptoms and
      maternal psychological control. Motivated by family systems theory and the
      transactions that occur between individual and dyadic levels of the family
      system, we examined the connections among these variables during a developmental
      period when children and parents experience significant psychosocial changes.
      Three years of self-report data were collected from 168 mother-adolescent dyads,
      beginning when the adolescents (55.4% girls) were in 6th grade. Models were
      tested using longitudinal path analysis. Results indicated that the connection
      between adolescent aggression (and depressive symptoms) and maternal
      psychological control was best characterized as adolescent-driven, indirect, and
      mediated by mother-adolescent conflict; there were no indications of parent
      driven indirect effects. That is, prior adolescent aggression and depressive
      symptoms were associated with increased conflict. In turn, conflict was
      associated with increased psychological control. Within our mediation models,
      reciprocal direct effects between both problem behaviors and conflict and between
      conflict and psychological control were also found. Additionally, exploratory
      analyses regarding the role of adolescent gender as a moderator of variable
      relations were conducted. These analyses revealed no gender-related patterns of
      moderation, whether moderated mediation or specific path tests for moderation
      were considered. This study corroborates prior research finding support for child
      effects on parenting behaviors during early adolescence.

PMID- 22612431
TI  - Metabotropic glutamate receptors (mGluR5) activate transient receptor potential
      canonical channels to improve the regularity of the respiratory rhythm generated
      by the pre-Botzinger complex in mice.
AB  - Metabotropic glutamate receptors (mGluRs) are hypothesized to play a key role in
      generating the central respiratory rhythm and other rhythmic activities driven by
      central pattern generators (e.g. locomotion). However, the functional role of
      mGluRs in rhythmic respiratory activity and many motor patterns is very poorly
      understood. Here, we used mouse respiratory brain-slice preparations containing
      the pre-Botzinger complex (pre-BotC) to identify the role of group I mGluRs
      (mGluR1 and mGluR5) in respiratory rhythm generation. We found that activation of
      mGluR1/5 is not required for the pre-BotC to generate a respiratory rhythm.
      However, our data suggest that mGluR1 and mGluR5 differentially modulate the
      respiratory rhythm. Blocking endogenous mGluR5 activity with 2-Methyl-6
      (phenylethynyl)pyridine (MPEP) decreases the inspiratory burst duration, burst
      area and frequency, whereas it increases the irregularity of the fictive eupneic
      inspiratory rhythm generated by the pre-BotC. In contrast, blocking mGluR1
      reduces the frequency. Moreover, the mGluR1/5 agonist 3,5-dihydroxyphenylglycine
      increases the frequency and decreases the irregularity of the respiratory rhythm.
      Based on previous studies, we hypothesized that mGluR signaling decreases the
      irregularity of the respiratory rhythm by activating transient receptor potential
      canonical (TRPC) channels, which carry a non-specific cation current (ICAN).
      Indeed, 3,5-dihydroxyphenylglycine (DHPG) application reduces cycle-by-cycle
      variability and subsequent application of the TRPC channel blocker 1-[2-(4
      methoxyphenyl)-2-[3-(4-methoxyphenyl)propoxy]ethyl]imidazole (SKF-96365)
      hydrochloride reverses this effect. Our data suggest that mGluR5 activation of
      ICAN-carrying TRPC channels plays an important role in governing the cycle-by
      cycle variability of the respiratory rhythm. These data suggest that modulation
      of TRPC channels may correct irregular respiratory rhythms in some central
      neuronal diseases.

PMID- 22612433
TI  - Father-child transmission of school adjustment: a prospective intergenerational
      study.
AB  - The intergenerational transmission of school adjustment was explored in a sample
      of 213 children and their fathers. The fathers were participants in a
      longitudinal study that began when they were in the 4th grade, and their children
      have been assessed at the ages of 21 months and 3, 5, and 7 years. Two components
      of school adjustment were measured: academic achievement and peer relations.
      Results show that the fathers' academic achievement and peer relations were
      directly related to the same factors in their offspring even when the fathers'
      educational attainment, and both the fathers' and the children's general
      cognitive abilities were included in the models. When potential mechanisms of
      intergenerational transmission were examined, father's age at the birth of the
      child, income, and educational expectations for the child were links in the
      transmission of academic achievement from one generation to the next. For peer
      relations across generations, income, inconsistent parenting, and educational
      expectations were links in transmission. Implications of these findings are
      considered, including the possibility that interventions to improve school
      adjustment in one generation might have significant and long-reaching effects for
      the next.

PMID- 22612434
TI  - Phonological skills and vocabulary knowledge mediate socioeconomic status effects
      in predicting reading outcomes for Chinese children.
AB  - This study examined the relations among socioeconomic status (SES), early
      phonological processing, vocabulary, and reading in 262 children from diverse SES
      backgrounds followed from ages 4 to 9 in Beijing, China. SES contributed to
      variations in phonological skills and vocabulary in children's early development.
      Nonetheless, early phonological and vocabulary abilities exerted equally strong
      and independent mediation of the SES effects on children's reading achievement by
      the end of 3rd grade for this Chinese sample. These findings not only replicate
      studies in alphabetic languages but, because of their longitudinal nature, also
      demonstrate the potential for interventions focused on improving children's early
      language skills, and at which ages these factors may have the greatest impact.

PMID- 22612436
TI  - Removing obstacles for African American English-speaking children through greater
      understanding of language difference.
AB  - Language difference among speakers of African American English (AAE) has often
      been considered language deficit, based on a lack of understanding about the AAE
      variety. Following Labov (1972), Wolfram (1969), Green (2002, 2011), and others,
      we define AAE as a complex rule-governed linguistic system and briefly discuss
      language structures that it shares with general American English (GAE) and others
      that are unique to AAE. We suggest ways in which mistaken ideas about the
      language variety add to children's difficulties in learning the mainstream
      dialect and, in effect, deny them the benefits of their educational programs. We
      propose that a linguistically informed approach that highlights correspondences
      between AAE and the mainstream dialect and trains students and teachers to
      understand language varieties at a metalinguistic level creates environments that
      support the academic achievement of AAE-speaking students. Finally, we present 3
      program types that are recommended for helping students achieve the skills they
      need to be successful in multiple linguistic environments.

PMID- 22612437
TI  - Is working memory training effective? A meta-analytic review.
AB  - It has been suggested that working memory training programs are effective both as
      treatments for attention-deficit/hyperactivity disorder (ADHD) and other
      cognitive disorders in children and as a tool to improve cognitive ability and
      scholastic attainment in typically developing children and adults. However,
      effects across studies appear to be variable, and a systematic meta-analytic
      review was undertaken. To be included in the review, studies had to be randomized
      controlled trials or quasi-experiments without randomization, have a treatment,
      and have either a treated group or an untreated control group. Twenty-three
      studies with 30 group comparisons met the criteria for inclusion. The studies
      included involved clinical samples and samples of typically developing children
      and adults. Meta-analyses indicated that the programs produced reliable short
      term improvements in working memory skills. For verbal working memory, these near
      transfer effects were not sustained at follow-up, whereas for visuospatial
      working memory, limited evidence suggested that such effects might be maintained.
      More importantly, there was no convincing evidence of the generalization of
      working memory training to other skills (nonverbal and verbal ability, inhibitory
      processes in attention, word decoding, and arithmetic). The authors conclude that
      memory training programs appear to produce short-term, specific training effects
      that do not generalize. Possible limitations of the review (including age
      differences in the samples and the variety of different clinical conditions
      included) are noted. However, current findings cast doubt on both the clinical
      relevance of working memory training programs and their utility as methods of
      enhancing cognitive functioning in typically developing children and healthy
      adults.

PMID- 22612438
TI  - Taking versus confronting visual perspectives in preschool children.
AB  - Recent evidence suggests that 3-year-olds can take other people's visual
      perspectives not only when they perceive different things (Level 1) but even when
      they see the same thing differently (Level 2). One hypothesis is that 3-year-olds
      are good perspective takers but cannot confront different perspectives on the
      same object (Perner, Stummer, Sprung, & Doherty, 2002). In 2 studies using color
      filters, 3-year-olds were unable to judge in what color they and an adult saw the
      same picture. This was the case irrespective of whether children replied verbally
      (pilot study) or by pointing to color samples (main study). However, 3-year-olds
      readily took an adult's perspective by determining which of 2 objects an adult
      referred to as being a certain color, independently from how the children saw the
      objects (main study). Taken together, these results suggest that preschoolers'
      difficulty is not so much taking perspectives as it is directly confronting
      another's view with their own-an ability that seems to be acquired between 4 and
      5 years of age.

PMID- 22612439
TI  - Infectious complications after esophagectomy.
AB  - BACKGROUND: Esophageal cancer is a serious diagnosis that has a relative
      incidence of 4/100,000 inhabitants in the Czech Republic. This disorder is
      managed predominantly by surgery. The steps to improving the outcome of treatment
      include a multifactorial approach. The role of operative technique in improving
      outcomes seems to have reached its limits. However, antibiotic prophylaxis and
      the treatment of complicating bacterial infections continue to play important
      roles. METHODS: A total of 85 patients with strictly defined antibiotic
      prophylaxis during surgical esophagectomy were included in our study. Bacterial
      strains were isolated from the patient's clinical materials after operation; only
      one strain from each patient, the first to be isolated, was tested for antibiotic
      sensitivity. RESULTS: Infectious complications were observed in 15.3% of patients
      and the mortality rate from infectious complications reached 30.8%. The most
      frequently documented complicated infection was pneumonia (69.2%) and the most
      frequent pathogens were enteric bacteria (56.5%). Some bacterial strains
      producing extended-spectrum beta-lactamases and AmpC beta-lactamases were found.
      CONCLUSIONS: The infections in our patient set were of endogenous origin. In
      cases of pneumonia, it is appropriate to begin with antibiotics effective against
      enteric bacteria and Pseudomonas aeruginosa.

PMID- 22612440
TI  - Disseminated Nocardia farcinica: literature review and fatal outcome in an
      immunocompetent patient.
AB  - BACKGROUND: Nocardia farcinica is a gram-positive, partially acid-fast,
      methenamine silver-positive aerobic actinomycete. Nocardia spp. are opportunistic
      pathogens, and N. farcinica is the least common species of clinical importance.
      METHODS: Review of the recent literature and description of a immunocompetent
      patient with no known risk factors who contracted fatal N. farcinica sepsis.
      RESULTS: Positive pre-mortem and post-mortem cultures from the lung and synovium
      correlated with acute bronchopneumonia and synovitis at autopsy. Colonies of
      filamentous bacteria, which were not apparent in conventional hematoxylin and
      eosin-stained sections, were observed with gram and methenamine silver stains,
      but acid-fast stains were negative. A literature review revealed that
      disseminated N. farcinica often is associated with an underlying malignant tumor
      or autoimmune disease (88% of patients). Chemotherapy or corticosteroid
      treatments are additional risk factors. CONCLUSIONS: Trimethoprim
      sulfamethoxazole typically is the first-line therapy for N. farcinica; treatment
      with amikacin and imipenem-cilastatin is used less often (7% of patients).
      Despite aggressive therapy, we observed that the death rate (39%) associated with
      N. farcinica in recent publications was eight percentage points higher than
      reported in a review from 2000.

PMID- 22612441
TI  - Electrophilic trifluoromethylation by copper-catalyzed addition of CF3-transfer
      reagents to alkenes and alkynes.
AB  - Regio- and stereoselective Cu-catalyzed addition of the above hypervalent iodine
      reagent to alkynes and alkenes was achieved. In the presence of CuI, the reaction
      is suitable to perform trifluoromethyl-benzoyloxylation and trifluoromethyl
      halogenation of alkenes and alkynes. Electron-donating substituents accelerate
      the process, and alkenes react faster than alkynes emphasizing the electrophilic
      character of the addition reaction.

PMID- 22612442
TI  - Syringocystadenoma papilliferum arising on the scrotum.
AB  - An 8-year-old boy presented to the pediatric dermatology service with an
      elevated, moist and vegetated pinkish mass, measuring 4 * 5 * 2 cm in diameter,
      located in the scrotum. The lesion has been gradually increasing in size showing
      a recent accelerated growth. Excisional biopsy demonstrated the histological
      picture of syringocystadenoma papilliferum (SCAP). The interest of this report
      lies in the rarity of syringocystadenoma papilliferum, its unusual presentation
      in the scrotum not yet reported in pediatric literature, and the importance of
      differential diagnoses in this location.

PMID- 22612443
TI  - Reproduction and embryogenesis of the mandi-amarelo catfish, Pimelodus maculatus
      (Pisces, Pimelodidae), in captivity.
AB  - To study reproduction and embryogenesis, Pimelodus maculatus specimens were kept
      in captivity and captured bimonthly during 1 year. Gonads samples (211 specimens)
      were collected and submitted to routine histological techniques. Pimelodus
      maculatus prepared to reproduce when water temperature was high, and even reached
      advanced maturation but did not spawn in captivity. Spent fish gonads were not
      documented, and atretic follicles were frequent (60%) in late maturation females.
      When then submitted to hypophysation, 70% of the females responded positively to
      hormonal treatment. Oocyte extrusion occurred 8 h after a second hormonal
      injection at 26 degrees C. The fertilisation rate was 65.1 +/- 9.2% at 24 degrees
      C. Recently spawned oocytes of P. maculatus were spherical, non-adhesive, yellow
      in colour, with an average diameter of 1113.92 +/- 37.02 MUm and covered by a
      thick gelatinous layer. Blastopore closure occurred 7 h and 30 min after
      fertilisation. Embryonic development was completed within 18 h after
      fertilisation. The results of this work provide important knowledge for the
      handling and cultivation of not only P. maculatus, but other species of potential
      value for fish culture.

PMID- 22612444
TI  - Where does work stress come from? A generalizability analysis of stress in police
      officers.
AB  - Differences among workers and workplace stressors both contribute to perceiving
      work as stressful. However, the relative importance of these sources to work
      stress is not well delineated. Moreover, the extent to which work stress
      additionally reflects unique matches between specific workers and particular job
      stressors is also unclear. In this study, we use generalizability theory to
      specify and compare sources of variance in stress associated with police work. US
      police officers (N = 115) provided ratings of 60 stressors commonly associated
      with policing duties. Primary and secondary stress appraisal ratings reflected
      differences among officers in tendencies to generally perceive work stressors as
      stressful (14-15% officer effect), and also agreement among officers in viewing
      some stressors as more stressful than others (18-19% stressor effect). However,
      ratings especially reflected distinct pairings of officers and stressors (38-41%
      interaction effect). Additional analyses revealed individual differences and
      stressor characteristics associated with each variance component, including an
      officer * stressor interaction - compared to officers low in neuroticism, highly
      neurotic officers provided lower primary appraisal ratings of stressors generally
      seen as not serious, and also higher primary appraisal ratings of stressors that
      were seen as serious. We discuss implications of the current approach for the
      continued study of stress at work.

PMID- 22612446
TI  - Role of ultrasound compared to age-related formulas for uncuffed endotracheal
      intubation in a pediatric population.
AB  - BACKGROUND: It is often difficult to determine the correct size of endotracheal
      tubes (ETT) needed for intubating pediatric patients. Therefore, we evaluated the
      role of ultrasound in pediatric patients to compare the correct size of an
      uncuffed (ETT) with the minimal transverse diameter of the subglottic airway
      (MTDSA) measured by ultrasound and with tube size predicted by different age
      related formulas. METHODS: A total of 50 pediatric patients <= 5 years were
      enrolled. As a standard, we defined the adequate ETT size with no audible leakage
      below a ventilation pressure of 15 mbar and with an audible leakage above 25
      mbar. The maximum allowed difference between the prediction method result and the
      ETT that fit was defined as 0.3 mm. Ultrasound was performed before the
      intubation procedure; the intubating anesthesiologists were blinded to the
      results of the ultrasound measurement. Agreement between the two age-based
      formulas most commonly used at our department and MTDSA with the correct ETT size
      (standard) was analyzed using a Bland-Altman plot. Correlation and regression
      analyses were performed and the numbers of correct intubation trials recorded.
      RESULTS: The frequency of bias <= 0.3 mm between each method and the correct ETT
      in the first attempt was <50% and the mean number of reintubations 1.6 +/- 1.3.
      In contrast to age-related formulas, however, the ultrasonographically determined
      MTDSA was not significantly different from the correct ETT. MTDSA was highly
      associated with the outer diameter of the ETT (r = 0.869, R(2) = 0.754).
      CONCLUSIONS: Measuring MTDSA by ultrasound facilitates selection of the
      appropriate ETT in pediatric patients and may reduce the number of reintubations.

PMID- 22612445
TI  - On death receptor 3 and its ligands....

PMID- 22612447
TI  - Understanding the behavioral determinants of retention in HIV care: a qualitative
      evaluation of a situated information, motivation, behavioral skills model of care
      initiation and maintenance.
AB  - The current study provides a qualitative test of a recently proposed application
      of an Information, Motivation, Behavioral Skills (IMB) model of health behavior
      situated to the social-environmental, structural, cognitive-affective, and
      behavioral demands of retention in HIV care. Mixed-methods qualitative analysis
      was used to identify the content and context of critical theory-based
      determinants of retention in HIV care, and to evaluate the relative fit of the
      model to the qualitative data collected via in-depth semi-structured interviews
      with a sample of inner-city patients accessing traditional and nontraditional HIV
      care services in the Bronx, NY. The sample reflected a diverse marginalized
      patient population who commonly experienced comorbid chronic conditions (e.g.,
      psychiatric disorders, substance abuse disorders, diabetes, hepatitis C). Through
      deductive content coding, situated IMB model-based content was identified in all
      but 7.1% of statements discussing facilitators or barriers to retention in HIV
      care. Inductive emergent theme identification yielded a number of important
      themes influencing retention in HIV care (e.g., acceptance of diagnosis, stigma,
      HIV cognitive/physical impairments, and global constructs of self-care). Multiple
      elements of these themes strongly aligned with the model's IMB constructs. The
      convergence of the results from both sets of analysis demonstrate that
      participants' experiences map well onto the content and structure of the situated
      IMB model, providing a systematic classification of important theoretical and
      contextual determinants of retention in care. Future intervention efforts to
      enhance retention in HIV care should address these multiple determinants (i.e.,
      information, motivation, behavioral skills) of self-directed retention in HIV
      care.

PMID- 22612448
TI  - Exploring the contribution of general self-efficacy to the use of self-care
      symptom management strategies by people living with HIV infection.
AB  - General self-efficacy (GSE), the expectation that one is able to perform a
      behavior successfully, may differentiate those who are able to successfully
      utilize self-care symptom management strategies (SCSMS). This subanalysis (n=569)
      of an international 12 site longitudinal randomized controlled trial (RCT)
      (n=775), investigated GSE as an important factor determining symptom burden,
      SCSMS, engagement with the provider, and medication adherence over time, and
      identified differences in those with high and low GSE ratings concerning these
      variables. Parametric and nonparametric repeated-measures tests were employed to
      assess GSE and the perceived effectiveness of SCSMS for anxiety, depression,
      diarrhea, fatigue, nausea, and neuropathy. Symptom burden, engagement with the
      provider, and antiretroviral adherence were analyzed with regard to GSE. Our data
      indicated that there were differences in the perceived symptom burden over time
      of HIV infected individuals by GSE. Those individuals with higher GSE had fewer
      symptoms and these symptoms were perceived to be less intense than those
      experienced by the low GSE group. There were few meaningful differences in the
      SCSMS used by those with high versus low GSE other than the use of illicit
      substances in the low GSE group. The low GSE group was also significantly (p= <
      0.001) less engaged with their healthcare providers. Given the difference in
      substance use by perceived GSE, and the importance of engagement with the
      healthcare provider, more attention to the resolution of the concerns of those
      with low GSE by healthcare providers is warranted.

PMID- 22612449
TI  - Strong metal-support interactions between gold nanoparticles and ZnO nanorods in
      CO oxidation.
AB  - The catalytic performances of supported gold nanoparticles depend critically on
      the nature of support. Here, we report the first evidence of strong metal-support
      interactions (SMSI) between gold nanoparticles and ZnO nanorods based on results
      of structural and spectroscopic characterization. The catalyst shows
      encapsulation of gold nanoparticles by ZnO and the electron transfer between gold
      and the support. Detailed characterizations of the interaction between Au
      nanoparticles and ZnO were done with transmission electron microscopy (TEM), X
      ray photoelectron spectroscopy (XPS), X-ray absorption spectroscopy (XAS),
      electron paramagnetic resonance (EPR), and FTIR study of adsorbed CO. The
      significance of the SMSI effect is further investigated by probing the efficiency
      of CO oxidation over the Au/ZnO-nanorod. In contrast to the classical reductive
      SMSI in the TiO(2) supported group VIII metals which appears after high
      temperature reduction in H(2) with electron transfer from the support to metals,
      the oxidative SMSI in Au/ZnO-nanorod system gives oxygen-induced burial and
      electron transfer from gold to support. In CO oxidation, we found that the
      oxidative SMSI state is associated with positively charged gold nanoparticles
      with strong effect on its catalytic activity before and after encapsulation. The
      oxidative SMSI can be reversed by hydrogen treatment to induce AuZn alloy
      formation, de-encapsulation, and electron transfer from support to Au. Our
      discovery of the SMSI effects in Au/ZnO nanorods gives new understandings of the
      interaction between gold and support and provides new way to control the
      interaction between gold and the support as well as catalytic activity.

PMID- 22612450
TI  - Activation of PAC(1)  and VPAC receptor subtypes elicits differential
      physiological responses from sympathetic preganglionic neurons in the
      anaesthetized rat.
AB  - BACKGROUND AND PURPOSE: Pituitary adenylate cyclase-activating polypeptide
      (PACAP) is an excitatory neuropeptide with central and peripheral cardiovascular
      actions. Intrathecal PACAP increases splanchnic sympathetic nerve activity and
      heart rate, but not mean arterial pressure (MAP). We hypothesize that the three
      PACAP receptors (PAC(1) , VPAC(1) and VPAC(2) ) have different actions in central
      cardiovascular control, and that their summed effect results in the lack of MAP
      response observed following intrathecal PACAP injection. EXPERIMENTAL APPROACH:
      The effects of the PACAP receptors on baseline cardiovascular parameters were
      investigated using selective agonists and antagonists administered into the
      intrathecal space of urethane-anaesthetized, vagotomized and artificially
      ventilated male Sprague-Dawley rats. KEY RESULTS: Selective activation of the
      PACAP receptors had different effects on MAP. When activated by maxadilan, PAC(1)
      receptors increased MAP. The VPAC receptors decreased MAP when both were
      activated with vasoactive intestinal polypeptide or when only VPAC(1) receptors
      were activated. The PAC(1) and VPAC(2) receptor antagonist PACAP(6-38) had no
      cardiovascular effects, suggesting that PACAP is not tonically released.
      CONCLUSIONS AND IMPLICATIONS: PACAP neurotransmission was not responsible for the
      moment-to-moment tonic regulation of central cardiovascular control mechanisms.
      Nevertheless, PACAP release within the spinal cord may have pleiotropic effects
      on sympathetic outflow depending on the postsynaptic receptor type. PAC(1) and
      VPAC receptor subtypes produced opposing changes in blood pressure when activated
      by intrathecal PACAP-38 in the anaesthetized Sprague-Dawley rat, resulting in no
      net change in MAP.

PMID- 22612452
TI  - Illness perception and quality of life in patients with contact dermatitis.
AB  - BACKGROUND: People's subjective perceptions of illness are important determinants
      of their ways of coping with health threats and the ensuing physical and mental
      outcomes, including quality of life (QoL), which has been consistently reported
      to be impaired by contact dermatitis. OBJECTIVES: To investigate the
      relationships of subjective illness perceptions and dermatological QoL in atopic,
      contact and occupational dermatitis patients and a comparison group of patients
      with other dermatological diseases. PATIENTS AND METHODS: Three hundred and three
      patients of four diagnostic groups filled in the Brief Illness Perception
      Questionnaire and the Skindex-16 (+ occupational impact items) Dermatological QoL
      questionnaire before clinical examination and patch testing. RESULTS: Perceptions
      of serious consequences, greater symptom burden and more uncertainty and worry
      were associated with lower QoL (r(s) > 0.50). Overall, patients reported low
      personal control over their condition and low understanding of the disease (3.5
      and 4.8, respectively, on a 0-10 scale). QoL was most impaired among occupational
      dermatitis patients (mean = 46) and least impaired among patients who were later
      diagnosed as suffering from conditions other than contact dermatitis (mean = 62).
      CONCLUSIONS: Identifying critical components of illness perceptions in patients
      with atopic, contact and occupational dermatitis may enable the design of
      consultations and interventions to fit patients' perceptions, which could affect
      their QoL.

PMID- 22612453
TI  - Solitary solid renal mass: can we predict malignancy?
AB  - What's known on the subject? and What does the study add? It is known that the
      majority (80%) of solid renal masses are malignant. Most of the literature
      suggests that smaller tumour size is associated with a higher incidence of benign
      disease. We have confirmed that decreased tumour size is associated with benign
      disease, particularly for lesions <2 cm. Once radiologically apparent
      angiomyolipomas are excluded, the incidence of benign disease with small renal
      masses is lower than reported in the literature (11%). Furthermore, we have shown
      that small renal masses in females have a higher association with benign disease.
      Patient age and tumour location were not predictive of benign histology. We have
      also stratified our risks not only for benign disease but also for clinically
      indolent renal cancers to help physicians counsel patients with regard to
      managing these solid renal masses. OBJECTIVE: * To determine the clinical
      predictors of benign disease in patients with solitary solid renal masses.
      PATIENTS AND METHODS: * Pathology reports of patients who underwent radical or
      partial nephrectomy at two hospitals from 1998 to 2008 were reviewed. * Only
      patients with solitary solid unilateral renal masses were included. * Predictors
      of malignancy risk were assessed with univariate and multivariate logistic
      regression analysis. RESULTS: * A total of 592 patients with a mean (sd) age of
      60 (13) years were included, 38% of whom were women. Radical and partial
      nephrectomy was performed in 66% and 34% of patients, respectively. * Renal
      masses were equally distributed on the right and left sides (49% vs 51%, P=
      0.84). Masses were more commonly located in the upper and lower poles than in the
      mid pole (40.8% vs 38.7% vs 20.5%, respectively). * The mean tumour size was
      larger in patients who underwent radical compared with partial nephrectomy (6.8
      cm vs 2.9 cm, P < 0.001). The rate of benign disease in our overall population
      was 9.5%. * On univariate and multivariate analysis, only a renal mass size <2 cm
      and female gender were predictive of benign disease. On further analysis the
      magnitude of this effect was found to be additive. CONCLUSIONS: * Renal masses <2
      cm and female gender were associated with a higher probability of benign disease.
      * Patient age and tumour location were not predictive of benign disease.

PMID- 22612451
TI  - Calpain 10 homology modeling with CYGAK and increased lipophilicity leads to
      greater potency and efficacy in cells.
AB  - Calpain 10 is a ubiquitously expressed mitochondrial and cytosolic Ca(2+)
      regulated cysteine protease in which overexpression or knockdown leads to
      mitochondrial dysfunction and cell death. We previously identified a potent and
      specific calpain 10 peptide inhibitor (CYGAK), but it was not efficacious in
      cells. Therefore, we created a homology model using the calpain 10 amino acid
      sequence and calpain 1 3-D structure and docked CYGAK in the active site. Using
      this model we modified the inhibitor to improve potency 2-fold (CYGAbuK). To
      increase cellular efficacy, we created CYGAK-S-phenyl-oleic acid heterodimers.
      Using renal mitochondrial matrix CYGAK, CYGAK-OC, and CYGAK-ON had IC(50)'s of
      70, 90, and 875 nM, respectively. Using isolated whole renal mitochondria CYGAK,
      CYGAK-OC, and CYGAK-ON had IC(50)'s of 95, 196, and >10,000 nM, respectively.
      Using renal proximal tubular cells (RPTC) in primary culture, 30 min exposures to
      CYGAK-OC and CYGAbuK-OC decreased cellular calpain activity approximately 20% at
      1 MUM, and concentrations up to 100 MUM had no additional effect. RPTC treated
      with 10 MUM CYGAK-OC for 24 h induced accumulation of ATP synthase beta and
      NDUFB8, two calpain 10 substrates. In summary, we used molecular modeling to
      improve the potency of CYGAK, while creating CYGAK-oleic acid heterodimers to
      improve efficacy in cells. Since calpain 10 has been implicated in type 2
      diabetes and renal aging, the use of this inhibitor may contribute to elucidating
      the role of calpain 10 in these and other diseases.

PMID- 22612455
TI  - The effect of Q factor on gross mechanical efficiency and muscular activation in
      cycling.
AB  - Unexplored in scientific literature, Q Factor describes the horizontal width
      between bicycle pedals and determines where the foot is laterally positioned
      throughout the pedal stroke. The aim of the study was to determine whether
      changing Q Factor has a beneficial effect upon cycling efficiency and muscular
      activation. A total of 24 trained cyclists (11 men, 13 women; VO2max 57.5
      ml.kg/min +/- 6.1) pedaled at 60% of peak power output for 5 min at 90 rpm using
      Q Factors of 90, 120, 150, and 180 mm. Power output and gas were collected and
      muscular activity of the gastrocnemius medialis (GM), tibialis anterior (TA),
      vastus medialis (VM), and vastus lateralis (VL) measured using surface
      electromyography. There was a significant increase (P < 0.006) in gross
      mechanical efficiency (GME) for 90 and 120 mm (both 19.38%) compared with 150 and
      180 mm (19.09% and 19.05%), representing an increase in external mechanical work
      performed of approximately 4-5 W (1.5-2.0%) at submaximal power outputs. There
      was no significant difference in the level of activity or timing of activation of
      the GM, TA, VM, and VL between Q Factors. Other muscles used in cycling, and
      possibly an improved application of force during the pedal stroke may play a role
      in the observed increase in GME with narrower Q Factors. 

PMID- 22612458
TI  - Online memory screening--are older adults interested and can it work?
AB  - Subjective memory concerns are common in older adults and may prompt the use of
      web-based cognitive screening. Websites which purport to provide memory screening
      are numerous and can influence health behaviours; however there is currently
      limited evidence regarding their validity. The current research aims to assess
      potential user's attitudes and motivations regarding online cognitive screening
      and to evaluate the preliminary evidence for the feasibility and validity of two
      subjective online cognitive measures. The sample consisted of community-based
      older adults, 30 with, and 30 without, memory concerns. Participants rated their
      likelihood of their accessing online cognitive screening and gave rationales.
      Participants' performance on objective pen and paper measures of cognition was
      compared to performance on subjective online screening measures. The majority of
      participants indicated they would access online cognitive screening. A total of
      100% of participants were able to use the online tools without assistance. None
      of the online measures was positively associated with the pen and paper screening
      measures. Anxiety and depression were significantly associated with subjective
      memory concerns. This study provided no supporting evidence for the validity of
      either subjective online screening measure assessed. Anxiety and depression were
      significantly associated with subjective cognition, indicating that, although
      they may not predict objective cognition, complaints about memory in older adults
      should be taken seriously by health professionals.

PMID- 22612457
TI  - The unexpected force of acute stroke leading to patients' sudden death as
      described by nurses.
AB  - Stroke occurs suddenly and unexpectedly and its consequences can mean the
      difference between life and death. Research into stroke is extensive but largely
      focused on patients who survive. The aim of the study was to describe how nurses
      experience the patient's death and dying, when patients are afflicted by acute
      stroke and whose lives cannot be saved. The study had a descriptive design with a
      hermeneutical approach. Interviews were carried out with ten nurses in stroke
      units at three hospitals. Data were interpreted using hermeneutic textual
      interpretation based on Gadamer's philosophy. The study shows that sudden death,
      when unexpected forces intervene in the lives of patients afflicted by acute
      stroke, was described by the main theme sudden death - the unexpected force and
      the following three sub-themes: death comes unexpectedly and without warning to
      the patient; the relatives are at the mercy of the unexpected and the nurses find
      themselves in demanding situations. The new understanding emphasizes that the
      unexpected and demanding situations the nurses are put in can be understood as
      ethical dilemmas and value conflicts because they are not free to give their time
      to preserving the dying patient's dignity and are not able to give the good care
      they wish to. A more flexible organization could support the nurses in making use
      of the creative forces in the unexpected event which an acute stroke that leads
      to death constitutes.

PMID- 22612459
TI  - Apricot DNA as an indicator for persipan: detection and quantitation in marzipan
      using ligation-dependent probe amplification.
AB  - The confectionery ingredient marzipan is exclusively prepared from almond kernels
      and sugar. The potential use of apricot kernels, so-called persipan, is an
      important issue for the quality assessment of marzipan. Therefore, a ligation
      dependent probe amplification (LPA) assay was developed that enables a specific
      and sensitive detection of apricot DNA, as an indicator for the presence of
      persipan. The limit of detection was determined to be 0.1% persipan in marzipan.
      The suitability of the method was confirmed by the analysis of 20 commercially
      available food samples. The integration of a Prunus -specific probe in the LPA
      assay as a reference allowed for the relative quantitation of persipan in
      marzipan. The limit of quantitation was determined to be 0.5% persipan in
      marzipan. The analysis of two self-prepared mixtures of marzipan and persipan
      demonstrated the applicability of the quantitation method at concentration levels
      of practical relevance for quality control. 

PMID- 22612460
TI  - Cu(I)-catalyzed regioselective synthesis of pyrazolo[5,1-c]-1,2,4-triazoles.
AB  - Cycloadditions of terminal alkynes to 1,2,4-triazolium N-imides in the presence
      of base and Cu(I) afford pyrazolo[5,1-c]-1,2,4-triazoles regioselectively. The
      scope of alkynes, the influence of the electronic nature of the leaving group,
      and variations in the 1-alkyl substituent were examined. Quantum chemical
      calculations were employed to explain the distinct reactivity of the propiolates.

PMID- 22612461
TI  - Beyond bevacizumab: new anti-VEGF strategies in colorectal cancer.
AB  - INTRODUCTION: Treatment of colorectal cancer (CRC) has changed dramatically over
      the past decade, mainly due to the advent of molecularly targeted agents. In
      particular, an improved understanding of the role of the angiogenesis pathway in
      CRC has led to advancements in treatment. Bevacizumab has been shown to improve
      the progression-free survival and overall survival when combined with cytotoxic
      chemotherapy in patients with metastatic CRC (mCRC) and at present is the only
      antiangiogenesis agent approved for the treatment of this cancer. AREAS COVERED:
      In this review, the authors outline the most recent data on the VEGF signaling
      pathway and on new therapeutic reagents that target it, provide insight into
      their mechanisms, and describe results from recent clinical trials. EXPERT
      OPINION: In the new decade of 'modern therapy', an increasing number of
      antiangiogenic agents for the treatment of mCRC are being tested in preclinical
      models, and dozens of studies on these drugs are ongoing. Presently, eight novel
      antiangiogenic agents are in Phase III trials and a wide range of other
      candidates are being tested in Phase I/II trials. Given the preliminary positive
      results of two recent Phase III trials, aflibercept and regorafenib, probably,
      will be new-targeted agents approved for the treatment of mCRC. Furthermore, the
      list of potentially approved agents seems to increase in the next years and to
      maximize their potential clinical impact, is critically important to introduce
      efficient molecular diagnostic methodologies into the drug development process to
      indentify the subset of patients who would benefit most from their use.

PMID- 22612462
TI  - Recent speciation between sympatric Tanganyikan cichlid colour morphs.
AB  - Lake Tanganyika, Africa's oldest lake, harbours an impressive diversity of
      cichlid fishes. Although diversification in its radiating groups is thought to
      have been initially rapid, cichlids from Lake Tanganyika show little evidence for
      ongoing speciation. In contrast, examples of recent divergence among sympatric
      colour morphs are well known in haplochromine cichlids from Lakes Malawi and
      Victoria. Here, we report genetic evidence for recent divergence between two
      sympatric Tanganyikan cichlid colour morphs. These Petrochromis morphs share
      mitochondrial haplotypes, yet microsatellite loci reveal that their sympatric
      populations form distinct genetic groups. Nuclear divergence between the two
      morphs is equivalent to that which arises geographically within one of the morphs
      over short distances and is substantially smaller than that among other sympatric
      species in this genus. These patterns suggest that these morphs diverged only
      recently, yet that barriers to gene flow exist which prevent extensive admixture
      despite their sympatric distribution. The morphs studied here provide an unusual
      example of active diversification in Lake Tanganyika's generally ancient cichlid
      fauna and enable comparisons of speciation processes between Lake Tanganyika and
      other African lakes.

PMID- 22612463
TI  - The role of parent depressive symptoms in positive and negative parenting in a
      preventive intervention.
AB  - This study examined the role of parent depressive symptoms as a mediator of
      change in behaviorally observed positive and negative parenting in a preventive
      intervention program. The purpose of the program was to prevent child problem
      behaviors in families with a parent who has current or a history of major
      depressive disorder. One hundred eighty parents and one of their 9- to 15-year
      old children served as participants and were randomly assigned to a family group
      cognitive-behavioral (FGCB) intervention or a written information (WI) comparison
      condition. At two months after baseline, parents in the FGCB condition had fewer
      depressive symptoms than those in the WI condition, and these symptoms served as
      a mediator for changes in negative, but not positive, parenting at 6 months after
      baseline. The findings indicate that parent depressive symptoms are important to
      consider in family interventions with a parent who has current or a history of
      depression.

PMID- 22612464
TI  - Catheter-related bloodstream infection caused by Enterococcus spp.
AB  - The role of Enterococcus spp. as a cause of catheter-related bloodstream
      infections (CR-BSI) is almost unexplored. We assessed the incidence and clinical
      characteristics of enterococcal CR-BSI (ECR-BSI) over an 8-year period in our
      hospital. We performed a retrospective study (January 2003 to December 2010) in a
      large teaching institution. We recorded the incidence, and the microbiological
      and clinical data from patients with ECR-BSI. The incidence per 10,000 admissions
      for enterococcal BSI and ECR-BSI was 25 and 1.7, respectively. ECR-BSI was the
      fourth leading cause of CR-BSI in our institution (6%). A total of 75 episodes of
      ECR-BSI were detected in 73 patients (6% of all enterococcal BSI). The incidence
      of ECR-BSI increased by 17% annually (95% CI 19.0-21.0%) during the study period.
      Nineteen percent of ECR-BSI episodes were polymicrobial. Overall mortality was
      33%. ECR-BSI is an emerging and increasingly common entity with a high mortality.
      This finding should be taken into account when selecting empirical treatment for
      presumptive CR-BSI.

PMID- 22612465
TI  - Onychomycosis in the Denver pediatrics population, a retrospective study.
AB  - Onychomycosis (OM) is a common nail disorder in adults but has been rare in
      children. Recent international studies have demonstrated a rise in the prevalence
      of OM in children and adolescents, with Trichophyton rubrum being the most common
      pathogen. This 5-year retrospective chart review of children (aged <18) found
      that 66 of 141 patients (46.8%) presenting to Children's Hospital Colorado or
      Denver Health Medical Center Dermatology clinics with nail complaints had OM,
      with the highest prevalence in those aged 6 to 10 and a slight male predominance.
      Toenails were more commonly affected, and Trichophyton rubrum was the most common
      pathogen. 

PMID- 22612466
TI  - Alkynyl phosphonate DNA: a versatile "click"able backbone for DNA-based
      biological applications.
AB  - Major hurdles associated with DNA-based biological applications include, among
      others, targeted cell delivery, undesirable nonspecific effects, toxicity
      associated with various analogues or the reagents used to deliver
      oligonucleotides to cells, and stability toward intracellular enzymes. Although a
      plethora of diverse analogues have been investigated, a versatile methodology
      that can systematically address these challenges has not been developed. In this
      contribution, we present a new, Clickable, and versatile chemistry that can be
      used to rapidly introduce diverse functionality for studying these various
      problems. As a demonstration of the approach, we synthesized the core analogue,
      which is useful for introducing additional functionality, the
      triazolylphosphonate, and present preliminary data on its biological properties.
      We have developed a new phosphoramidite synthon--the alkynyl phosphinoamidite,
      which is compatible with conventional solid-phase oligonucleotide synthesis.
      Postsynthesis, the alkynylphosphonate can be functionalized via "Click" chemistry
      to generate the 1,2,3-triazolyl or substituted 1,2,3-triazolyl phosphonate-2'
      deoxyribonucleotide internucleotide linkage. This manuscript describes the
      automated, solid-phase synthesis of mixed backbone oligodeoxyribonucleotides
      (ODNs) having 1,2,3-triazolylphosphonate (TP) as well as phosphate or
      thiophosphate internucleotide linkages and also 2'-OMe ribonucleotides and locked
      nucleic acids (LNAs) at selected sites. Nuclease stability assays demonstrate
      that the TP linkage is highly resistant toward 5'- and 3'-exonucleases, whereas
      melting studies indicate a slight destabilization when a TP-modified ODN is
      hybridized to its complementary RNA. A fluorescently labeled 16-mer ODN modified
      with two TP linkages shows efficient cellular uptake during passive transfection.
      Of particular interest, the subcellular distribution of TP-modified ODNs is
      highly dependent on cell type; a significant nuclear uptake is observed in HeLa
      cells, whereas diffuse cytoplasmic fluorescence is found in the WM-239A cell
      line. Cytoplasmic distribution is also present in human neuroblastoma cells (SK-N
      F1), but Jurkat cells show both diffuse and punctate cytoplasmic uptake. Our
      results demonstrate that triazolylphosphonate ODNs are versatile additions to the
      oligonucleotide chemist's toolbox relative to designing new biological research
      reagents.

PMID- 22612467
TI  - Vascular endothelial growth factor -634G/C polymorphism associated with
      osteonecrosis of the femoral head in a Chinese population.
AB  - An impeded blood flow through the femoral head is incriminated in the
      etiopathogenesis of osteonecrosis of the femoral head (ONFH). Vascular
      endothelial growth factor (VEGF) is a strong angiogenic protein and also plays a
      role in the formation of cartilage and bone. The aim of this study was to
      evaluate the association of VEGF -634G/C polymorphism with ONFH in a Chinese
      population. A total of 220 unrelated patients with nontraumatic ONFH and 220
      unrelated control subjects were consecutively enrolled in a hospital-based case
      control study. A polymerase chain reaction-restriction fragment length
      polymorphism analysis was used to detect the VEGF -634G/C genotype. Patients with
      ONFH had a significantly higher frequency of the CC genotype (odds ratio=1.64,
      95% confidence interval=1.03, 2.60; p=0.04) than controls. There were no
      significant associations between any genotypes and the cause of ONFH. Our results
      support the hypothesis that the VEGF -634CC genotype is a risk factor of ONFH in
      the Chinese population. However, current results should be validated
      prospectively in larger cohorts.

PMID- 22612468
TI  - Factors associated with nonadherence to antiretroviral therapy in HIV-positive
      smokers.
AB  - Adherence to antiretroviral therapy (ART) has markedly improved HIV disease
      management, and significantly reduced HIV/AIDS-associated morbidity and
      mortality. Although recent studies suggest a relationship between smoking and
      suboptimal adherence to ART, a more in-depth understanding of this relationship
      is needed. We conducted a secondary analysis using data from a randomized
      controlled smoking cessation trial to investigate the association of nonadherence
      to ART with potential demographic, psychosocial (perceived stress and
      depression), and substance use (nicotine dependence, illicit drug use, and
      alcohol use) variables among persons living with HIV/AIDS (PLWHA) who smoke. The
      mean (standard deviation [SD]) age of participants (n=326) was 45.9 years old
      (SD=7.6). Additionally, the majority were male (72.1%), self-identified as black
      (76.7%), and reported sexual contact as the mode of HIV acquisition (70%).
      Unadjusted logistic regression analysis indicated that depression (odds ratio
      [OR]=1.02; 95% confidence interval [CI]=1.00, 1.04), illicit drug use (OR=2.39;
      95% CI=1.51, 3.79) and alcohol use (OR=2.86; 95%CI=1.79, 4.57) were associated
      with nonadherence. Adjusted logistic regression analysis indicated that nicotine
      dependence (OR=1.13; 95% CI=1.02, 1.25), illicit drug use (OR=2.10; 95% CI=1.27,
      3.49), alcohol use (OR=2.50; 95% CI=1.52, 4.12), and age (OR=1.04; 95% CI=1.00,
      1.07) were associated with nonadherence. Nicotine dependence, illicit drug use,
      and alcohol use are potentially formidable barriers to ART adherence among PLWHA
      who smoke. Future efforts should investigate the complex relationships among
      these variables to improve adherence particularly among populations confronted
      with multifaceted health challenges.

PMID- 22612469
TI  - Patient-reported symptoms on the antiretroviral regimen
      efavirenz/emtricitabine/tenofovir.
AB  - Most patients (80-90%) newly diagnosed with HIV are started on the antiretroviral
      regimen efavirenz, emtricitabine, and tenofovir (EFV/FTC/TDF). Existing studies
      of patient tolerability, however, are limited. We compared symptom experiences of
      patients on EFV/FTC/TDF, and the subsequent impact on health-related quality of
      life, with those of patients on other combination antiretroviral therapy (cART).
      We conducted a cross-sectional analysis of the Veterans Aging Cohort Study from
      February 2008 to August 2009 to compare the symptom experiences of patients on
      EFV/FTC/TDF vs. other cART, unadjusted and then adjusted for treatment
      characteristics, and comorbid disease severity. We then assessed the association
      between EFV/FTC/TDF use and health-related quality of life. Among the 1,759
      patients in our analytic sample, EFV/FTC/TDF use was associated with fewer
      symptoms than was other cART. The use of EFV/FTC/TDF was independently associated
      with health-related quality of life, and this association was at least partially
      explained by symptom burden.

PMID- 22612470
TI  - Mentalization as a moderator of treatment effects: findings from a randomized
      clinical trial for personality disorders.
AB  - Mentalization is the capacity to understand behavior as expressions of various
      mental states. It is assumed to be important for understanding the underlying
      psychopathology, the therapeutic process, and the outcome of therapy associated
      with patients with personality disorders (PDs). However, to date, empirical
      findings are scarce and inconsistent. This study aimed to examine whether the pre
      treatment level of mentalization, operationalized as Reflective Functioning (RF),
      was associated with differential responses to two different treatment modalities
      and might predict clinical improvement. We analyzed data from a randomized
      clinical trial (Ulleval Personality Project). Seventy-eight patients with
      borderline and/or avoidant PD had been randomly assigned to either a step-down
      treatment program or outpatient individual psychotherapy. The step-down treatment
      comprised short-term day hospital treatment, followed by long-term, combined
      group and individual psychotherapy. RF was rated before treatment and after 36
      months. Outcome measures were administered at baseline and after 8, 18, and 36
      months. The moderator analyses indicated that patients with low RF levels at
      baseline responded better to outpatient individual psychotherapy than to the step
      down treatment in terms of improvements in psychosocial functioning. Patients
      with medium-high RF levels responded equally well to both therapy formats.
      Determining which therapy format is appropriate for specific groups of patients
      can improve treatment efficiency. Therefore, our findings may have important
      clinical implications. Future research should address RF as a mediator of change.

PMID- 22612471
TI  - Exploring the complexity of supramolecular interactions for patterning at the
      liquid-solid interface.
AB  - The use of self-assembly to fabricate surface-confined adsorbed layers (adlayers)
      from molecular components provides a simple means of producing complex functional
      surfaces. The molecular self-assembly process relies on supramolecular
      interactions sustained by noncovalent forces such as van der Waals,
      electrostatic, dipole-dipole, and hydrogen bonding interactions. Researchers have
      exploited these noncovalent bonding motifs to construct well-defined two
      dimensional (2D) architectures at the liquid-solid interface. Despite myriad
      examples of 2D molecular assembly, most of these early findings were
      serendipitous because the intermolecular interactions involved in the process are
      often numerous, subtle, cooperative, and multifaceted. As a consequence, the
      ability to tailor supramolecular patterns has evolved slowly. Insight gained from
      various studies over the years has contributed significantly to the knowledge of
      supramolecular interactions, and the stage is now set to systematically engineer
      the 2D supramolecular networks in a "preprogrammed" fashion. The control over 2D
      self-assembly of molecules has many important implications. Through appropriate
      manipulation of supramolecular interactions, one can "encode" the information at
      the molecular level via structural features such as functional groups,
      substitution patterns, and chiral centers which could then be retrieved,
      transferred, or amplified at the supramolecular level through well-defined
      molecular recognition processes. This ability allows for precise control over the
      nanoscale structure and function of patterned surfaces. A clearer understanding
      and effective use of these interactions could lead to the development of
      functional surfaces with potential applications in molecular electronics, chiral
      separations, sensors based on host-guest systems, and thin film materials for
      lubrication. In this Account, we portray our various attempts to achieve rational
      design of self-assembled adlayers by exploiting the aforementioned complex
      interactions at the liquid-solid interface. The liquid-solid interface presents a
      unique medium to construct flawless networks of surface confined molecules. The
      presence of substrate and solvent provides an additional handle for steering the
      self-assembly of molecules. Scanning tunneling microscopy (STM) was used for
      probing these molecular layers, a technique that serves not only as a
      visualization tool but could also be employed for active manipulation of
      molecules. The supramolecular systems described here are only weakly adsorbed on
      a substrate, which is typically highly oriented pyrolytic graphite (HOPG).
      Starting with fundamental studies of substrate and solvent influence on molecular
      self-assembly, this Account describes progressively complex aspects such as
      multicomponent self-assembly via 2D crystal engineering, emergence, and induction
      of chirality and stimulus responsive supramolecular systems.

PMID- 22612472
TI  - Comparison of partial vs radical nephrectomy with regard to other-cause mortality
      in T1 renal cell carcinoma among patients aged >=75 years with multiple
      comorbidities.
AB  - OBJECTIVE: To quantify the effect of partial nephrectomy (PN) vs radical
      nephrectomy (RN) on other-cause mortality (OCM) in elderly patients with
      localized renal cell carcinoma (RCC) and/or multiple comorbidities. METHODS:
      Using the Surveillance, Epidemiology, and End Results Medicare-linked database,
      patients with T1 RCC, aged >=75 years, or who had >=2 comorbidities, were
      identified (1988-2005). To adjust for inherent differences between treatment
      types, propensity-based matched analyses were performed. Competing-risks
      regression analyses for prediction of OCM were assessed according to treatment
      type. The effect of PN and RN on OCM was examined in three sub-groups: patients
      aged >=75 years; patients with >=2 comorbidities; and patients aged >=75 years
      with >=2 comorbidities. RESULTS: After propensity-based matched analyses and
      adjustment for all covariates, PN was found to exert a protective effect relative
      to RN with respect to OCM in all patients (hazard ratio [HR]: 0.84, P = 0.048).
      In subanalyses, no difference was recorded between PN and RN in patients who were
      aged >=75 years (HR: 0.83, P = 0.2), with >=2 baseline comorbidities at diagnosis
      (HR: 0.83, P = 0.1), or in patients who were aged >=75 years and who had >=2
      baseline comorbidities (HR: 0.77, P = 0.2). CONCLUSIONS: Some elderly patients
      and/or those with multiple comorbidities at diagnosis may not benefit from PN
      with respect to OCM. After rigorous patient selection, alternative treatment
      options could be considered.

PMID- 22612473
TI  - Children with specific language impairment show difficulties in sensory
      modulation.
AB  - The purpose of this study is to investigate whether a group of 116 Dutch children
      with specific language impairment (SLI) shows differences in sensory processing
      when compared to a control group of age-matched 4-7-year-old typical peers. The
      Sensory Profile-NL-a standardized questionnaire of 125 items-was completed by
      caregivers of children in both groups. Children with SLI differed significantly
      from the control group on all 14 section scores and 4 quadrant scores of the
      Sensory Profile-NL. The effect size of the difference in sensory modulation
      patterns of children with and without SLI on this measure was large (Cohen's d >=
      0.80). Difficulties in sensory modulation can be characterized as frequent co
      morbid problems in children with SLI.

PMID- 22612474
TI  - Special issue on the impact of endocrine disrupters on reproductive health.

PMID- 22612475
TI  - Urinary phthalate excretion in 555 healthy Danish boys with and without pubertal
      gynaecomastia.
AB  - Pubertal gynaecomastia is a clinical sign of an oestrogen-androgen imbalance,
      which occurs in 40-60% of adolescent Caucasian boys. In most cases no underlying
      endocrinopathy can be identified. A recent study reports higher plasma phthalate
      levels in Turkish boys with pubertal gynaecomastia. Therefore, we asked whether
      there was an association between concurrent measures of urinary phthalate
      metabolites and pubertal timing as well as the presence of gynaecomastia in
      otherwise healthy boys. We studied a total of 555 healthy boys (age 6.07-19.83
      years) as part of the COPENHAGEN Puberty Study. Anthropometry and pubertal stages
      (PH1-6 and G1-5) were evaluated, and the presence of gynaecomastia was assessed.
      Non-fasting blood samples were analysed for serum testosterone and morning urine
      samples were analysed for the total content of 12 phthalate metabolites (MEP,
      MnBP, MiBP, MBzP, MEHP, MEHHP, MEOHP, MECPP, MiNP, MHiNP, MiONP and MCiOP) by LC
      MS/MS. A statistically significant negative correlation was observed between
      chronological age and the urinary concentration of the sum of measured
      metabolites DEHP (?DEHPm) (r = -0.164) and DiNP (?DiNPm) (r = -0.224),
      respectively, and the sum of monobutyl phthalate (MBP) isomers (?MBP((i+n))) (r =
      -0.139) (all with p < 0.01). In contrast urinary monoethyl phthalate
      concentration was positively correlated to age (r = 0.187, p < 0.01). The urinary
      levels of phthalate metabolites were not associated with age at pubertal onset,
      serum testosterone levels or presence of gynaecomastia. In conclusion, we did not
      find evidence of anti-androgenic effects of phthalates in our healthy boys. Thus,
      current phthalate exposure was not associated with pubertal timing, testosterone
      levels or with the presence of pubertal gynaecomastia in this cross-sectional
      study. However, longitudinal studies are needed to evaluate possible perinatal or
      long-term postnatal effects of phthalates on healthy boys.

PMID- 22612477
TI  - Modelling defined mixtures of environmental oestrogens found in domestic animal
      and sewage treatment effluents using an in vitro oestrogen-mediated
      transcriptional activation assay (T47D-KBluc).
AB  - There is growing concern of exposure of fish, wildlife and humans to water
      sources contaminated with oestrogens and the potential impact on reproductive
      health. Environmental oestrogens can come from various sources including
      concentrated animal feedlot operations (CAFO), municipal waste, agricultural and
      industrial effluents. US EPA's drinking water contaminant candidate list 3 (CCL3)
      includes several oestrogenic compounds. Although these contaminants are currently
      not subject to any proposed or promulgated national primary drinking water
      regulations, they are known or anticipated to occur in public water systems and
      may require future regulation under the Safe Drinking Water Act. Using an in
      vitro transcriptional activation assay, this study evaluated oestrogens from CCL3
      both individually and as a seven oestrogen mixture (fixed ray design) over a
      broad range of concentrations, including environmentally relevant concentrations.
      Log EC(50) and Hillslope values for individual oestrogens were as follows:
      estrone, -11.92, 1.283; estradiol-17alpha, -9.61, 1.486; estradiol-17beta, 11.77,
      1.494; estriol, -11.14, 1.074; ethinyl estradiol-17alpha, -12.63, 1.562;
      Mestranol, -11.08, 0.809 and Equilin, -11.48, 0.946. In addition, mixtures that
      mirrored the primary oestrogens found in swine, poultry and dairy CAFO effluent
      (fixed-ratio ray design), and a ternary mixture (4 * 4 * 4 factorial design) of
      oestrogens found in hormone replacement therapy and/or oral contraceptives were
      tested. Mixtures were evaluated for additivity using both the concentration
      addition (CA) model and oestrogen equivalence (EEQ) model. For each of the
      mixture studies, a broad range of concentrations were tested, both above and
      below environmentally relevant concentrations. Results show that the observed
      data did not vary consistently from either the CA or EEQ predictions for any
      mixture. Therefore, either the CA or EEQ model should be useful predictors for
      modelling oestrogen mixtures.

PMID- 22612476
TI  - Paracetamol (acetaminophen), aspirin (acetylsalicylic acid) and indomethacin are
      anti-androgenic in the rat foetal testis.
AB  - More than half the pregnant women in the Western world report taking mild
      analgesics. These pharmaceutical compounds have been associated with congenital
      cryptorchidism in humans, the best-known risk factor for low semen quality and
      testicular germ cell cancer. Furthermore, some of these mild analgesics exert
      potent anti-androgenic effects in the male rat and several endocrine-disrupting
      compounds, known to alter masculinization, have also been shown to be potent
      inhibitors of prostaglandin (PG) synthesis similar to mild analgesics. Using a 3
      day ex vivo organotypic model system based on gestational day 14.5 rat testes, we
      herein show that testosterone production was inhibited by paracetamol, at doses
      of 0.1 MUm to 100 MUm. Similar results were obtained for aspirin (1-100 MUm) and
      indomethacin (10 MUm). The production of the other Leydig cell hormone, Insl3,
      was not disrupted by exposure to paracetamol. Investigations of the gross anatomy
      of the testis as well as Leydig cells number and rate of gonocyte apoptosis after
      the 3 days of ex vivo differentiation showed no significant effect of the
      analgesics tested compared with controls. These data indicate therefore that mild
      analgesics specifically inhibit testosterone production in rat foetal testes in
      vitro and that these compounds had no effect on gonocyte survival. Parallel
      determinations of prostaglandin D2 (PGD2) production indicated that the effects
      of paracetamol and aspirin on PGD2 and testosterone were not connected, whereas
      the effects of indomethacin were correlated. We conclude that mild analgesics
      exert direct and specific anti-androgenic effects in rat foetal testis in our
      experimental setup and that the mechanism of action is probably uncoupled from
      the inhibition of PG synthesis.

PMID- 22612478
TI  - Sunscreens: are they beneficial for health? An overview of endocrine disrupting
      properties of UV-filters.
AB  - Today, topical application of sunscreens, containing ultraviolet-filters (UV
      filters), is preferred protection against adverse effects of ultraviolet
      radiation. Evidently, use of sunscreens is effective in prevention of sunburns in
      various models. However, evidence for their protective effects against melanoma
      skin cancer is less conclusive. Three important observations prompted us to
      review the animal data and human studies on possible side effects of selected
      chemical UV-filters in cosmetics. (1) the utilization of sunscreens with UV
      filters is increasing worldwide; (2) the incidence of the malignant disorder for
      which sunscreens should protect, malignant melanoma, is rapidly increasing and
      (3) an increasing number of experimental studies indicating that several UV
      filters might have endocrine disruptive effects. The selected UV-filters we
      review in this article are benzophenone-3 (BP-3), 3-benzylidene camphor (3-BC), 3
      (4-methyl-benzylidene) camphor (4-MBC), 2-ethylhexyl 4-methoxy cinnamate (OMC),
      Homosalate (HMS), 2-ethylhexyl 4-dimethylaminobenzoate (OD-PABA) and 4
      aminobenzoic acid (PABA). The potential adverse effects induced by UV-filters in
      experimental animals include reproductive/developmental toxicity and disturbance
      of hypothalamic-pituitary-thyroid axis (HPT). Few human studies have investigated
      potential side effects of UV-filters, although human exposure is high as UV
      filters in sunscreens are rapidly absorbed from the skin. One of the UV-filters,
      BP-3, has been found in 96% of urine samples in the US and several UV-filters in
      85% of Swiss breast milk samples. It seems pertinent to evaluate whether exposure
      to UV-filters contribute to possible adverse effects on the developing organs of
      foetuses and children.

PMID- 22612479
TI  - A new and useful method for the macrocyclization of linear peptides.
AB  - A new and useful procedure for the macrocyclization of linear peptides is
      described. The natural amino acid side chains of tyrosine (phenol), lysine
      (alkylamine), and histidine (imidazole) react in an intramolecular fashion with a
      pendent pyridine-N-oxide-carboxamide, which is selectively activated by the
      phosphonium salt, PyBroP. The reaction is mild, rapid, and efficient with a
      potentially large substrate scope. Multiple examples are provided with full
      characterization and analyses, including a novel aza-variant of the C-O-D ring
      system of vancomycin.

PMID- 22612480
TI  - Medical anthropology in Europe: shaping the field.

PMID- 22612481
TI  - Medical anthropologists in Europe connect.

PMID- 22612483
TI  - Medical anthropology at home.

PMID- 22612482
TI  - Alien origins: xenophilia and the rise of medical anthropology in the
      Netherlands.
AB  - The beginnings of medical anthropology in the Netherlands have a 'xenophile'
      character in two respects. First, those who started to call themselves medical
      anthropologists in the 1970s and 1980s were influenced and inspired not so much
      by anthropological colleagues, but by medical doctors working in tropical
      countries who had shown an interest in the role of culture during their medical
      work. Secondly, what was seen as medical anthropology in those early days almost
      always took place in 'foreign' countries and cultures. One can hardly
      overestimate the exoticist character of medical anthropology up to the 1980s. It
      was almost automatic for anthropologists to take an interest in medical issues
      occurring in another cultural setting, while overlooking the same issues at home.
      Medical anthropology 'at home' started only around 1990. At present, medical
      anthropology in the Netherlands is gradually overcoming its xenophile
      predilection.

PMID- 22612484
TI  - Itineraries and specificities of Italian medical anthropology.
AB  - This paper describes the birth (or rebirth) of Italian medical anthropology
      around the middle of the 1950s, and its subsequent complex development up to the
      present. During this fairly long process, the author played a role that was
      probably of some importance, that of both a direct witness and active
      participant. Here these developments are briefly reviewed, in an attempt to
      single out some of the stimuli and the most significant occasions that have
      happened, their theoretical and methodological reference points, the main lines
      of research that have been tackled along the way, as well as the 'social demand'
      and the 'social use' that have integrated and oriented the practice of the new
      discipline within the horizon of some of the more general problems of Italian
      society. In outlining here the profile of and the various events in Italian
      medical anthropology, this paper takes into account the fact that, although a
      medical anthropology with that name and the disciplinary set-up that are now
      internationally attributed to it began in Italy only in the mid-1950s, important
      lines of research to which we would today attach that name had been undertaken
      long ago.

PMID- 22612485
TI  - Before and after fieldwork: ingredients for an ethnography of illness.
AB  - W.H.R. Rivers asked what light anthropology could throw on the emergence of
      medicine. But this early lead was not soon followed up. Social anthropology had
      first to establish itself. The new social anthropology championed holistic
      fieldwork in small-scale societies. Some did choose to study illness or
      misfortune ethnographically. Evans-Pritchard, Victor Turner and Max Marwick
      provided outstanding models in this field. Political change and decolonisation
      made some of the older assumptions about the place and aims of anthropological
      research less easy to sustain. Growth in the subject encouraged specialisation.
      Medical anthropology was one among many possible developments. But it also had to
      identify a distinctive focus and place in relation to medicine and other health
      related social studies.

PMID- 22612486
TI  - The beginnings of medical anthropology in France.

PMID- 22612487
TI  - What about Ethnomedizin? Reflections on the early days of medical anthropologies
      in German-speaking countries.
AB  - This paper gives an overview of the historical and theoretical developments of
      Ethnomedizin in Germany, Austria and Switzerland. It demonstrates the richness of
      this interdisciplinary field at the interface of anthropology, medicine and
      public health, and provides the unique perspectives of some of its founders from
      the 1970s onwards.

PMID- 22612488
TI  - Medical anthropology: the working group within the German Anthropological
      Association.

PMID- 22612489
TI  - Medical anthropology in Switzerland.

PMID- 22612490
TI  - Studying medical technologies.

PMID- 22612491
TI  - Medical anthropology in Europe--quo vadis?

PMID- 22612492
TI  - Chronicity and control: framing 'noncommunicable diseases' in Africa.
AB  - This paper proposes a way of framing the study of 'noncommunicable diseases'
      within the more general area of chronic conditions. Focusing on Africa, it takes
      as points of departure the situation in Uganda, and the approach to health issues
      developed by a group of European and African colleagues over the years. It
      suggests a pragmatic analysis that places people's perceptions and practices
      within a field of possibilities shaped by policy, health care systems, and life
      conditions. In this field, the dimensions of chronicity and control are the
      distinctive analytical issues. They lead on to consideration of patterns of
      sociality related to chronic conditions and their treatment.

PMID- 22612493
TI  - 'I am also a human being!' Antiretroviral treatment in local moral worlds.
AB  - The experiences and practices of antiretroviral drug consumers in Tanzania are
      shaped by economic scarcity, limited state-provided social welfare, and fragile
      kinship-based solidarity. Embedding antiretroviral therapy (ART) in patients'
      'local moral worlds' brings further existential dimensions to the fore that
      articulate closely with the priority the treatment acquires in their lives. An
      exemplary case study of a middle-aged HIV-positive man suggests that dignity,
      social recognition, and belonging may be of central interest and temporarily
      overshadow patients' concern for mere survival. A stronger focus on patients'
      moral concerns contributes to a better understanding of the complex dynamics that
      prevent HIV-positive people from becoming the 'pharmaceutical selves' that are
      promoted during treatment enrolment. Moreover, it is indispensable to account for
      the lived experiences of patients struggling with what too readily has been
      termed a 'chronic disease'.

PMID- 22612494
TI  - 'When there were only gods, then there was no disease, no need for doctors':
      forsaken deities and weakened bodies in the Indian Himalayas.
AB  - In this study the author analyzes the relationship between the individual body
      and the body politic in a region of the north Indian state of Uttarakhand, in
      connection with social changes occurring at the local and trans-local level,
      which are impacting the status of the different healing systems. By investigating
      these issues, this paper aims to shed light on some of the complex ways in which
      practitioners and patients who take part in a local method of healing, in this
      case ritual healing through possession, respond to the expansion of biomedicine.

PMID- 22612495
TI  - Second nature: on Gramsci's anthropology.
AB  - The aim of this paper is to convey the relevance of a Gramscian perspective in
      medical anthropology, stressing his anti-essentialist way of reasoning about
      'nature'. The author claims that Gramsci's understandings of the bodily life of
      the state can deconstruct naturalized realities in ways that are helpful for the
      ethnographer engaged in the political anthropology of embodiment and the
      management of health, persons, and life itself. The paper is presented in three
      parts. An attempt is made, first, to frame the relevance of Gramsci for Italian
      medical anthropology and second, to explore the components of the Gramscian
      concept of 'second nature' within the perspective that he himself calls 'an
      anthropology'. Third, an example is given of how the proposed Gramscian insights
      could inform an ethnography on the biopolitical aspects for the early detection
      of Alzheimer's disease, which is currently being carried out in Perugia.

PMID- 22612496
TI  - Of divinatory connaissance in South-Saharan Africa: the bodiliness of perception,
      inter-subjectivity and inter-world resonance.
AB  - Branching out from recent perspectives on divination in Africa, this study
      explores a fresh approach that engages in a constructive dialogue between local
      knowledge practices and Western-derived human sciences. A first section positions
      this essay within an emerging debate over the perspectival ontological turn in
      anthropology - in line with Viveiros de Castro (2004) - which holds that people's
      culture-specific ontology - such as, envisaging some propensity in the fabric
      between the human, things, fauna, flora and inter-worldly force-fields - is most
      explicitly voiced in the divinatory oracle and expressed in the ensuing healing
      and societal redress. The study then outlines the post-Lacanian matrixial model,
      defined by Ettinger ( 2006 ), that re-examines the originary processes unlocking,
      and inter-connecting in, the matrixial borderzone between body and psyche of
      mother and foetus or infans. A second section then focuses on the oracular
      scrutiny typically employed by the mediumistic Yaka diviner in southwestern DR
      Congo. Such practice, it is contended, induces the diviner to sense out in the
      consulting kin group the bewitching force-effects and the unspeakable in the
      inter-generational realm. The oracle unconceals some unguessed fate in the
      client's inter-generational line, in particular the inter-corporeal embeddedness
      of latent memory traces and forces of ill-bearing. Third, the study will conclude
      by evaluating - along the terms of the local culture's genius - the perspectivist
      stance and matrixial model.

PMID- 22612497
TI  - Health care decisions by Sukuma 'peasant intellectuals': a case of radical
      empiricism?
AB  - Health care decisions in Sukuma-speaking rural communities in Tanzania reproduce
      a practical epistemology that could be described as radically empiricist, rather
      than just pluralist; their point of reference is the deeper 'relation' between
      events, which collective traditions articulate and subjects may experience, but
      which escapes the atomistic perception privileged by biomedicine. This analysis
      relies on a diverse portfolio of ethnographic data, including the use and
      structure of medicinal recipes, the choices of mental health care according to
      experienced 'effectiveness', and lay discussions on the correct aetiology and
      treatment of reproductive disorder. Combining two dimensions for a given medical
      epistemology, the (empirical/ habitual) basis of its transmission and the
      (open/closed) relation with other epistemologies, four types are proposed:
      monism, dualism, pluralism, and radical empiricism. The concept of peasant
      intellectuals, it is argued, needs to be rethought in contexts of medicinal
      initiation.

PMID- 22612498
TI  - THE CANON--3: The harmony of illusions: inventing post-traumatic stress disorder,
      by Allan Young.

PMID- 22612500
TI  - Lung natural killer cells in mice: phenotype and response to respiratory
      infection.
AB  - Natural killer (NK) cells have a specialized function in peripheral organs, which
      is determined by the organ-specific niches. We have attempted to explore whether
      lung NK cells display a particular phenotype according to their function in the
      unique pulmonary environment in health or during respiratory infection in mice.
      In healthy mice, higher frequencies of NK cells among lymphocytes were detected
      in the lung than in other tissues (lymph node, bone marrow, spleen, blood and
      liver), and lung NK cells maintained a more mature phenotype, implying that lung
      NK cells were critical for the pulmonary immune response. However, lung NK cells
      expressed higher levels of inhibitory receptors and lower levels of activating
      receptors, migration/adhesion-associated molecules and co-stimulatory molecules
      than splenic NK cells, implying that lung NK cells were quiescent, and the
      activation of lung NK cells was tightly regulated by the pulmonary environment in
      health. During respiratory infection, lung NK cells could be activated and
      express functional molecules (CD107a and interferon-gamma) to take part in the
      response to infection quickly. These results suggested that the unique pulmonary
      environment promotes the development of NK cells with a lung-specific phenotype.

PMID- 22612502
TI  - JAK inhibition for the treatment of rheumatoid arthritis: a new era in oral DMARD
      therapy.
AB  - INTRODUCTION: In rheumatoid arthritis (RA) there is a significant medical need
      for safe and effective oral disease-modifying anti-rheumatic drugs (DMARDs) for
      patients who respond inadequately to methotrexate, the first-line therapy in RA.
      Oral agents targeting Janus-associated kinases (JAKs) are the most promising new
      agents in clinical development. This review describes the preclinical and
      clinical activities of the most advanced JAK inhibitors with different JAK
      selectivity profiles. AREAS COVERED: This review first describes the current
      treatment landscape and the pathophysiology of RA. Role for cytokines in the
      disease pathogenesis followed by significance of JAK/STAT pathway in cytokine
      signaling are discussed. Available chemical description and enzymatic data on the
      most advanced JAK inhibitors in clinical development are provided. Preclinical
      and clinical results that are publicly available are summarized. Review of
      literature was conducted using National Library of Medicine (NLM) database,
      'PubMed'. In addition, all publicly disclosed data from companies that are
      developing the JAK inhibitors was researched to obtain the most up-to-date
      information of the compounds discussed in this report. EXPERT OPINION: Emerging
      clinical results demonstrate that JAK inhibition is a validated new mechanism for
      the development of oral DMARD agents that is likely to join the armamentarium
      against RA in the near future.

PMID- 22612501
TI  - Leucine-rich glioma inactivated 1 (Lgi1), an epilepsy-related secreted protein,
      has a nuclear localization signal and localizes to both the cytoplasm and the
      nucleus of the caudal ganglionic eminence neurons.
AB  - Leucine-rich glioma inactivated 1 (Lgi1) is a secreted synaptic protein that
      organizes a transsynaptic protein complex throughout the brain. Mutations in the
      Lgi1 gene have been found in patients with autosomal dominant lateral temporal
      lobe epilepsy (ADLTE). Although a large number of studies have focused on the
      expression and function of Lgi1 in the postnatal brain, information regarding its
      functions and distribution during development remains sparse. Here we report that
      Lgi1 mRNA is preferentially expressed in the caudal ganglionic eminence (CGE) of
      the early embryonic telencephalon, and LGI1 protein is unexpectedly localized in
      the nucleus of dissociated CGE neurons. Using bioinformatics analysis, we found
      that LGI1 contains a putative nuclear localization signal (NLS) in its leucine
      rich repeat C-terminal domain. Furthermore, we show that the transient expression
      of Lgi1 in CGE neurons resulted in nuclear translocation of the LGI1 protein, and
      a mutation in the NLS led to the retention of LGI1 in the cytoplasm. We also
      confirmed that the NLS sequence of LGI1 had the ability to mediate the nuclear
      localization by using the NLS-containing fusion protein. Interestingly, when Lgi1
      was expressed in neurons obtained from the medial ganglionic eminence or cerebral
      cortex, almost no nuclear localization of LGI1 was observed. These results raise
      the possibility of a novel role of Lgi1 within embryonic neurons through nuclear
      translocation and may provide insight into its potential effects on the
      development of the central nervous system and ADLTE pathogenesis.

PMID- 22612503
TI  - A non-Karplus effect: evidence from phosphorus heterocycles and DFT calculations
      of the dependence of vicinal phosphorus-hydrogen NMR coupling constants on lone
      pair conformation.
AB  - In contrast to literature reports of a Karplus-type curve that correlates
      (3)J(PH) with phosphorus-hydrogen dihedral angle, a recently reported glycine
      derived 1,3,2-oxazaphospholidine (7c) has two hydrogen atoms on the ring with
      identical PNCH dihedral angles but measured coupling constants of ~6 and 1.5 Hz.
      DFT calculations were in accord with these values and suggested that the smaller
      coupling constant is negative. Experimental evidence of the opposite signs of
      these coupling constants was obtained by analysis of the ABX NMR spectrum of the
      new glycine-derived N-p-toluenesulfonyl phosphorus heterocycle 6c. DFT
      calculations on 6c and on Me(2)NPCl(2) and t-BuPCl(2) were also in accord with
      NMR data and allowed confirmation of unusual features including a lone pair
      effect on (3)J(PH), the negative coupling constant, temperature-dependent
      chemical shifts due to rotation about the sulfonamide S-N bond, and vicinal
      phosphorus-hydrogen coupling constants over 40 Hz. Calculation of phosphorus
      hydrogen coupling constants both as a function of PYCH dihedral angle theta (Y =
      O, N, C) and lone pair-PYC dihedral angle omega shows similar theta,omega
      surfaces for (3)J(PH) with a range of (3)J(PH) from -4.4 to +51 Hz and
      demonstrates the large non-Karplus effect of lone-pair conformation on vicinal
      phosphorus-hydrogen coupling constants.

PMID- 22612504
TI  - Change of editorship.

PMID- 22612505
TI  - Development of ulcerative colitis and its associated colorectal neoplasia as a
      model of the organ-specific chronic inflammation-carcinoma sequence.
AB  - The organ-specific chronic inflammation-carcinoma sequence was summarized and
      proposed. As a typical model, the ulcerative colitis (UC)--UC-associated
      carcinoma sequence was selected, and the mechanism of development of UC and UC
      associated carcinoma was reviewed, referring mainly to our data. Intestinal
      commensal bacteria, including Fusobacterium varium, obtained from the colonic
      mucosa of UC patients, can enter colonic epithelia and induce secretion of
      inflammatory cytokines, resulting in early inflammatory lesions consisting of
      cryptitis and crypt abscess. Inflammatory oxidative stress causes epithelial cell
      DNA-damage followed by p53 dependent G1 checkpoint activation and overloading,
      which causes p53 mutation. In long-standing UC, mucosal remodeling, including
      possible loss of crosstalk between epithelium and stroma may be critical for the
      development of UC-associated carcinoma, as well as accumulation of early p53
      mutation at the crypt level and increase of other stem cell mutated crypts,
      telomere shortening, and genomic instability of epithelial and stromal cells,
      including subepithelial myofibroblasts (corresponding to colonic stellate cells
      or Ito cells) and interstitial cells. Thus, the stochastic (probabilistic)
      pathway to tumor development over time gains commonalty through chronic
      inflammation stimulation. For the prevention of cancer development, appropriate
      anti-inflammatory therapy is important with an accurate assessment of the
      inflammation status in the colorectum.

PMID- 22612506
TI  - Combined evaluation of CK5/6, ER, p63, and MUC3 for distinguishing breast
      intraductal papilloma from ductal carcinoma in situ.
AB  - The differentiation of intraductal papilloma (IDP) in the breast from ductal
      carcinoma in situ (DCIS) is sometimes difficult. Fifty papillary lesions (25 DCIS
      and 25 IDP) were immunohistochemically examined using a panel of antibodies,
      including CK5/6, ER, p63, Ki-67, chromogranin A, synaptophysin, neuron specific
      enolase, CD56, MUC1, MUC3, CD44, p21, p27, and p53. The immunohistochemical
      staining pattern of each antibody was evaluated using the Allred scoring system.
      Then, the area under curve (AUC) for each antibody was computed by receiver
      operating characteristic (ROC) analysis. DCIS typically showed high scores for ER
      and MUC3 reactivity compared with IDP, and the AUC for ER and MUC3 were 0.941 and
      0.908, respectively. In contrast, IDP showed high scores for CK5/6 and p63
      reactivity compared with DCIS, and the AUC for CK5/6 and p63 were 1.00 and 0.954,
      respectively. We devised a 'Differential Index' (DI) using the following formula:
      [S(ER) + S(MUC3)]/[S(CK5/6) + S(p63) + 1]. The distributions of the DI for IDP
      and DCIS did not overlap when the cutoff value was placed arbitrarily at DI =
      1.0. From these results, it is concluded that a panel of four CK5/6, ER, p63, and
      MUC3 antibodies provide valuable information for differentiating IDP from DCIS.

PMID- 22612507
TI  - Correlations of TOP2A gene aberrations and expression of topoisomerase IIalpha
      protein and TOP2A mRNA expression in primary breast cancer: a retrospective study
      of 86 cases using fluorescence in situ hybridization and immunohistochemistry.
AB  - Our aim in this study was to assess the status of TOP2A gene aberrations (no
      change/amplification or deletion) and its correlations with topoisomerase IIalpha
      (Topo IIalpha) protein and TOP2A mRNA expression, respectively. TOP2A
      amplification, Topo IIalpha protein expression and TOP2A mRNA expression were
      assessed using samples of 86 cases of breast cancer by fluorescence in
      fluorescence in situ hybridization, quantitative real-time polymerase chain
      reaction and immunohistochemistry, respectively. Twenty two (22.57%) had
      amplification/deletion of TOP2A gene. Twenty eight (32.56%) tumor samples were
      17q polysomy or monosomy. Topo IIalpha protein was expressed in 57 cases (66.27%,
      57/86): 22 cases (38.62%, 22/57) and 35 cases (61.40%, 35/57) had
      amplification/deletion and no change of TOP2A gene, respectively. These three
      groups showed significant differences by one-way analysis of variance (P <
      0.001). The average Ct values of TOP2A mRNA expression in the tumors with
      deletion, amplification and no change of TOP2A gene were 27.00, 27.33 and 31.66,
      respectively. We demonstrated that the TOP2A gene was amplified or deleted in
      breast cancer, with a significant correlation with high expressions of Topo
      IIalpha protein and TOP2A mRNA expression. Ki-67 expression index (mean = 14.9)
      decreased significantly in cases wherein TOP2A gene had no change and Her2/neu
      protein expression was weakly positive (0-1+, P < 0.001).

PMID- 22612508
TI  - Apoptotic cells in peripheral blood and multiple organ injury.
AB  - To evaluate the roles of apoptotic cells in peripheral blood (PB) on multiple
      organ injury, five patients with hematopoietic stem cell transplantation (HSCT)
      and one with refractory anemia were examined. The following findings were
      confirmed. 1) High-dose alkylating agents were administrated as conditioning
      regimens to all HSCT patients. 2) Many organs were injured in all cases. 3)
      Neutrophils accumulated in the capillaries of injured organs, and endothelial
      cells were extensively injured. 4) Large numbers of apoptotic cells and
      gammaH2AX(+)  cells were observed in the foci of large cells with hyperchromatic
      nuclei. 5) Increased numbers of apoptotic cells (6/6), gammaH2AX(+)  cells (6/6),
      scavenger receptor A positive (SRA(+) ) cells (6/6), and tumor necrosis factor
      (TNF)-alpha(+)  cells (5/6) were observed in PB smear preparations. 6) Cytokines
      exceeded the normal levels in most patients. From these findings, apoptotic cells
      were considered to be produced by the administration of high-dose alkylating
      agents in HSCT patients, and apoptotic cells and SRA(+)  cells in PB were thought
      to play important roles in the development of multiple organ injury in HSCT and
      MDS patients.

PMID- 22612509
TI  - Ubiquitin-related proteins in neuronal and glial intranuclear inclusions in
      intranuclear inclusion body disease.
AB  - Recent studies have shown that eosinophilic intranuclear inclusions (INI) in the
      brain of patients with intranuclear inclusion body disease (INIBD) are
      immunopositive for ubiquitin and ubiquitin-related proteins (URP). However, the
      extent and frequency of URP-immunoreactive inclusions in INIBD are uncertain. We
      immunohistochemically examined the brain, spinal cord and dorsal root ganglia
      from five patients with INIBD, using a virtual slide system with sequential
      staining of the same sections with hematoxylin and eosin and by immunolabeling
      with antibodies against ubiquitin and URP (NEDD8, NUB1, SUMO-1 and SUMO-2).
      Intranuclear inclusions were widely distributed in neurons and glial cells in all
      the cases. Sequential staining revealed that 100% of INI in neurons and glial
      cells were positive for ubiquitin. Moreover, the majority or a significant
      proportion of INI were positive for NEDD8, NUB1, SUMO-1 and SUMO-2. However, the
      proportions of NEDD8-, NUB1- and SUMO-1-positive inclusions were significantly
      higher in neurons than in glial cells (P < 0.05). These findings suggest that
      proteins related to ubiquitination and proteasomal degradation are involved in
      the formation of INI in INIBD.

PMID- 22612510
TI  - Epstein-Barr virus-positive lymphoproliferative disorder associated with old
      organized chronic subdural hematoma.
AB  - This report describes a case of an immunocompetent 77-year-old male with Epstein
      Barr virus (EBV)-positive lymphoproliferative disorder associated with calcified
      chronic subdural hematoma (CSH). On the day prior to consultation in our
      outpatient clinic, the patient fell from his bed, striking his frontal head on
      the floor. Magnetic resonance imaging showed ill-defined lesions in the right
      frontal-temporal subdural regions. At surgery, a hard and thickened outer
      membrane of a CSH and muddy organized subdural hematoma were observed. However,
      macroscopic neoplastic lesions were not apparent. Histologically, there were
      atypical lymphoid cells scattered or conglomerated in some areas of the thick
      outer membrane of the CSH. They were composed of occasional large atypical
      lymphoid cells. The lesions were accompanied by necrosis. Atypical lymphoid cells
      were immunopositive for B-cell markers but not for T-cell markers. EBNA2 was seen
      in the nuclei of tumor cells. Atypical lymphoid cells showed positive signals for
      EBV-encoded small RNAs (EBERs) on in situ hybridization. These findings were
      consistent with EBV-positive lymphoproliferative disorder associated with CSH.
      These results also suggested that EBV and the inflammatory reaction found in the
      CSH could be the etiological factors in the pathogenesis of lymphoproliferative
      disorder.

PMID- 22612511
TI  - Autopsy case of amebic granulomatous meningoencephalitis caused by Balamuthia
      mandrillaris in Japan.
AB  - Balamuthia mandrillaris is a free-living ameba that causes amebic encephalitis.
      Herein, we report an autopsy case of Balamuthia encephalitis proven with
      polymerase chain reaction (PCR) and immunohistochemistry from paraffin-embedded
      brain biopsy specimens. A 68-year-old Japanese male presented at a hospital with
      progressive right hemiparesis approximately 3 months before his death. An open
      brain biopsy specimen showed diffuse meningitis with massive coagulative
      necrosis. The perivascular spaces contained numerous lymphocytes, histiocytes and
      giant cells, although the etiology was not determined. The patient deteriorated
      into coma and died from cerebral herniation. Autopsy revealed abundant
      trophozoites and cysts in the subarachnoid and Virchow-Robin's spaces. Electron
      micrographs of the amebic cysts showed a characteristic triple-walled envelope.
      The amebas were identified as Balamuthia mandrillaris based on
      immunohistochemical analysis from the autopsy and biopsy specimens. Primer sets
      designed to amplify approximately 200 bp bands of mitochondrial 16S rRNA gene of
      Balamuthia by PCR produced positive results from the biopsy specimens but
      negative results from the autopsy specimens. In summary, PCR to amplify shorter
      segments of DNA may be of diagnostic value in detecting suspected cases of
      balamuthiasis in formalin-fixed, paraffin-embedded specimens. Increased awareness
      and timely diagnosis of Balamuthia encephalitis might lead to earlier initiation
      of therapy and improved outcome.

PMID- 22612512
TI  - Primary pulmonary epithelioid angiosarcoma presenting as a solitary pulmonary
      nodule on image.
AB  - Primary angiosarcoma of lung is a rare condition. Only about 20 cases have
      appeared in English published reports so far. Its rarity and consequent low index
      of suspicion makes clinical diagnosis difficult. Pathological diagnosis of the
      epithelioid variant of pulmonary angiosarcoma is particularly challenging. We
      report a case of primary pulmonary epithelioid angiosarcoma as a solitary
      pulmonary nodule in image study in a 41-year-old man with a brief review, to
      contribute it to the sparse literature on this disease.

PMID- 22612513
TI  - Mucinous cystadenocarcinoma of the breast with a basal-like immunophenotype.
AB  - Mucinous cystadenocarcinoma (MCA) of the breast is extremely rare and was only
      recently described as a distinct variant of invasive ductal carcinoma of the
      breast. A case of MCA is reported in a 41-year-old woman. Mammographic and
      ultrasonographic examinations showed an irregularly shaped 10.0 * 8.0 * 5.5 cm
      lesion with patching calcification in the upper outer quadrant of the left
      breast. The gross examination revealed that the tumor has a well-circumscribed
      edge with a gelatinous cut surface and hemorrhage and necrosis were also noticed
      in the mass. Microscopically, the mass resembled mucinous cystic neoplasm of the
      ovary and pancreas closely, with cystic areas lined by columnar mucinous cells
      and associated with abundant extracellular and intracellular mucin, which is
      distinctively different from mucinous carcinoma with typically nests of low grade
      neoplastic cells floating in the mucin pool. The tumor cells were positive for
      CK7, CK20 and CDX2 were negative and displayed a typical immunophenotype of basal
      like breast cancer (ER, PR, HER2 were negative, CK5/6 and EGFR were positive).
      Metastatic carcinoma was identified in three of 14 axillary lymph nodes. We
      describe here a very unusual case of breast MCA with basal-like immunophenotype.

PMID- 22612515
TI  - Sebaceous carcinoma with apocrine differentiation (seboapocrine carcinoma).

PMID- 22612514
TI  - Autopsy case of primary myelofibrosis in which myeloid sarcoma was the initial
      manifestation of tumor progression.
AB  - Myeloid sarcoma (MyS) is defined as an extramedullary tumor-forming neoplasm
      consisting of immature myeloid cells with/without maturation. We experienced a
      case involving a 68-year-old Japanese male patient who had been followed-up for
      four years with a diagnosis of chronic idiopathic myelofibrosis/primary
      myelofibrosis (PMF) and noticed a painful mass in his left axilla. A wedge biopsy
      characterized the lesion as MyS that displayed megakaryoblastic/megakaryocytic
      differentiation. As his complete blood count included a few myeloid blasts (1% of
      WBC) and a bone marrow biopsy detected fibrosis without evidence of acute
      myelogenous leukemia (AML), a diagnosis of extramedullary blastic transformation
      of PMF was made, which was confirmed later by V617F mutation in Janus kinase-2 in
      both initial bone marrow biopsy and axillary tumor biopsy specimens. The patient
      died of pneumonia eight months after developing the axillary tumor. At autopsy,
      multiple MyS masses were detected in his soft tissue, but his bone marrow only
      contained fibrosis. Although MyS rarely develops before the leukemic
      transformation of PMF, no evidence of AML could be found in the patient's bone
      marrow at any point during the course of his disease. Thus, it is possible that
      the blasts in his peripheral blood were derived from the remaining MyS.
      Furthermore, the present case indicates that extramedullary blastic
      transformation, which is occasionally seen in CML, can also occur in PMF.
      Therefore, it is important to recognize that there is a wide variation in the
      pathogeneses of MyS and PMF.

PMID- 22612516
TI  - A case of intravenous lobular capillary hemangioma of the renal vein mimicking
      renal cell carcinoma.

PMID- 22612517
TI  - Differential insulin response to myo-inositol administration in obese polycystic
      ovary syndrome patients.
AB  - Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, chronic
      anovulation, polycystic ovaries at ultrasound evaluation, and quite frequently by
      insulin resistance or compensatory hyperinsulinemia. Attention has been given to
      the role of inositol-phosphoglycan (IPG) mediators of insulin action and growing
      evidences suggest that a deficiency of D-chiro-inositol (DCI) containing IPG
      might be at the basis of insulin resistance, frequent in PCOS patients. On such
      basis, we investigated the efficacy on insulin sensitivity and hormonal
      parameters of 8 weeks treatment with myo-inositol (MYO) (Inofert, ItalPharmaco,
      Milano, Italy) at the dosage of 2 g day in a group (n = 42) of obese PCOS
      patients,. After the treatment interval body mass index (BMI) and insulin
      resistance decreased together with luteinizing hormone (LH), LH/FSH and insulin.
      When subdividing the patients according to their fasting insulin levels, Group A
      (n = 15) insulin below 12 uU/ml and Group B (n = 27) insulin above 12 uU/ml, MYO
      treatment induced similar changes in both groups but only patients of Group B
      showed the significant decrease of both fasting insulin plasma levels (from 20.3
      +/- 1.8 to 12.9 +/- 1.8 uU/ml, p < 0.00001) and of area under the curve (AUC) of
      insulin under oral glucose tolerance test (OGTT). In conclusion, our study
      supports the hypothesis that MYO administration is more effective in obese
      patients with high fasting insulin plasma levels.

PMID- 22612518
TI  - Reconstruction of caribou evolutionary history in Western North America and its
      implications for conservation.
AB  - The role of Beringia as a refugium and route for trans-continental exchange of
      fauna during glacial cycles of the past 2million years are well documented; less
      apparent is its contribution as a significant reservoir of genetic diversity.
      Using mitochondrial DNA sequences and 14 microsatellite loci, we investigate the
      phylogeographic history of caribou (Rangifer tarandus) in western North America.
      Patterns of genetic diversity reveal two distinct groups of caribou. Caribou
      classified as a Northern group, of Beringian origin, exhibited greater number and
      variability in mtDNA haplotypes compared to a Southern group originating from
      refugia south of glacial ice. Results indicate that subspecies R. t. granti of
      Alaska and R. t. groenlandicus of northern Canada do not constitute
      distinguishable units at mtDNA or microsatellites, belying their current status
      as separate subspecies. Additionally, the Northern Mountain ecotype of woodland
      caribou (presently R. t. caribou) has closer kinship to caribou classified as
      granti or groenlandicus. Comparisons of mtDNA and microsatellite data suggest
      that behavioural and ecological specialization is a more recently derived life
      history characteristic. Notably, microsatellite differentiation among Southern
      herds is significantly greater, most likely as a result of human-induced
      landscape fragmentation and genetic drift due to smaller population sizes. These
      results not only provide important insight into the evolutionary history of
      northern species such as caribou, but also are important indicators for managers
      evaluating conservation measures for this threatened species.

PMID- 22612519
TI  - Intimate partner violence: a predictor of worse HIV outcomes and engagement in
      care.
AB  - For HIV-infected patients, experiencing multiple traumas is associated with AIDS
      related and all-cause mortality, increased opportunistic infections, progression
      to AIDS, and decreased adherence to therapy. The impact of intimate partner
      violence (IPV) on adherence and HIV outcomes is unknown. HIV-infected patients
      recruited from a public HIV clinic participated in this observational cohort
      study (n=251). Participants completed interviews evaluating IPV and covariates.
      CD4 count <200 (CD4<200), detectable HIV viral load (VL), and engagement in care
      ("no show rate" [NSR]) were the outcomes of interest. Medication adherence was
      not measured. Univariate and multivariate regression analyses were performed with
      covariates included if p<0.3 in the univariate phase. Seventy-four percent of the
      participants were male, 55% Caucasian, and 52.2% self-identified as "men who have
      sex with men." IPV prevalence was 33.1% with no difference by gender or sexual
      orientation. In univariate analysis, IPV exposure predicted having a CD4<200
      (p=0.005) and a detectable VL (p=0.04) but trended toward significance with a
      high NSR (p=0.077). Being threatened by a partner was associated with a CD4<200
      (p=0.005), a detectable VL (p=0.011), and high NSR (p=0.019) in univariate
      analysis. In multivariate analysis, IPV predicted having a CD4<200 (p=0.005) and
      detectable VL (p=0.035). Being threatened by a partner predicted having a CD4<200
      (p=0.020), a detectable VL (p=0.007), and a high NSR (p=0.020). Our results
      suggest IPV impacts biologic outcomes and engagement in care for HIV-infected
      patients. IPV alone predicts worse biologic outcomes, whereas the specific
      experience of being threatened by a partner was associated with all three
      outcomes in univariate and multivariate analyses.

PMID- 22612520
TI  - Development of a broad-specificity monoclonal antibody-based immunoaffinity
      chromatography cleanup for organophosphorus pesticide determination in
      environmental samples.
AB  - An immunoaffinity chromatographic (IAC) method for the selective extraction and
      concentration of 13 organophosphorus pesticides (OPs, including coumaphos,
      parathion, phoxim, quinalphos, dichlofenthion, triazophos, azinphos-ethyl,
      phosalone, isochlorthion, parathion-methyl, cyanophos, disulfoton, and phorate)
      prior to analysis by high-performance liquid chromatography-tandem mass
      spectrometry (HPLC-MS/MS) was developed. The IAC column was prepared by
      covalently immobilizing a monoclonal antibody with broad specificity for OPs on
      CNBr-activated Sephrose 4B. The column capacity ranged from 884 to 2641 ng/mL of
      gel. The optimum elution solvent was 0.01 M phosphate-buffered saline containing
      80% methanol. The breakthrough volume of the IAC column was found to be 400 mL.
      Recoveries of OPs from spiked environmental samples by IAC cleanup and HPLC-MS/MS
      analysis ranged from 60.2 to 107.1%, with a relative standard deviation below
      11.1%. The limit of quantitation for 13 OPs ranged from 0.01 to 0.13 ng/mL
      (ng/g). The application of IAC cleanup coupled to HPLC-MS/MS in real
      environmental samples demonstrated the potential of this method for the
      determination of OP residues in environmental samples at trace levels. 

PMID- 22612521
TI  - Effect of temperature and antimicrobial resistance on survival of  Campylobacter
      jejuni in well water: application of the Weibull model.
AB  - AIMS: The aims of this study were to measure the survival of two Campylobacter
      jejuni strains and their in vitro-challenged antimicrobial-resistant variants in
      well water, to evaluate the effects of antimicrobial resistance on survival and
      to develop a mathematical model for predicting the survival of Camp. jejuni in
      well water in the temperature range from 4 to 25 degrees C. METHODS AND RESULTS:
      The survival in log CFU ml-1 of two Camp. jejuni strains and their antimicrobial
      resistant variants was studied in well water stored at 4, 10, 15, 20 and 25
      degrees C. At 4 degrees C, the estimated 4-log CFU ml-1 decrease in ciprofloxacin
      resistant variant ATCC33560CIP32 was 55.2 days, significantly longer (P < 0.05)
      than that of resistant variant 49/7RATCIP32 (the estimated 4-log CFU ml-1
      decrease was 29.9 days). The respective times for the wild-type strains were 49.8
      and 60.4 days. The decrease in counts of Camp. jejuni was most dependent on
      temperature, because at 4 degrees C, the estimated t (4D) varied from 29.9 to
      60.4 days and at 25 degrees C from 3.7 to 5.7 days. CONCLUSIONS: Campylobacter
      jejuni survived in well water for long periods, especially at 4 degrees C, and
      the effect of ciprofloxacin resistance on fitness and survival was strain and
      temperature dependent. Weibull model was found to fit the data in the
      temperatures from 4 to 25 degrees C. SIGNIFICANCE AND IMPACT OF THE STUDY: In
      water environment Camp. jejuni is exposed to a wide spectrum of temperatures,
      which affects its survival and potential to cause waterborne infections.
      Antimicrobial resistance in Camp. jejuni is increasing, and minor data exist on
      the effect of antimicrobial resistance on the survival of Camp. jejuni. Water is
      an important source of campylobacteriosis; thus, we need to have modelling data
      to predict the survival characteristics of these organisms in water.

PMID- 22612522
TI  - Salivary cortisol response to stress in young children with atopic dermatitis.
AB  - Poor responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis under stress
      may be one explanation for stress-induced exacerbation of atopic dermatitis (AD)
      symptoms. In previous studies, children and adults with AD showed attenuated
      salivary cortisol responses to psychosocial stress, suggesting hyporesponsiveness
      of the HPA axis, but few studies have been conducted in young children, who are
      vulnerable to systemic side effects of topical corticosteroid (TCS) therapy. We
      evaluated whether salivary cortisol responses to the stress of venipuncture in
      young children with AD were related to the severity of AD or performance of TCS
      therapy. We studied 38 young children with AD (median age 16.5 mos, range 3-66
      mos) being treated at our outpatient unit. Patients were divided into three
      groups according to the scoring of atopic dermatitis index: mild (n = 12),
      moderate (n = 14), and severe (n = 12). To evaluate the responsiveness of the HPA
      axis to stress, salivary cortisol was determined before and after venipuncture.
      Salivary cortisol responsiveness to stress correlated negatively with severity of
      AD (p = 0.048) but not with previous use of TCS (p = 0.43) in young children with
      AD. Our findings suggest that the disease activity of AD, rather than TCS use, is
      responsible for HPA axis dysfunction in children with AD.

PMID- 22612523
TI  - Mononuclear metal-O2 complexes bearing macrocyclic N-tetramethylated cyclam
      ligands.
AB  - Metalloenzymes activate dioxygen to carry out a variety of biological reactions,
      including the biotransformation of naturally occurring molecules, oxidative
      metabolism of xenobiotics, and oxidative phosphorylation. The dioxygen activation
      at the catalytic sites of the enzymes occurs through several steps, such as the
      binding of O(2) at a reduced metal center, the generation of metal-superoxo and 
      peroxo species, and the O-O bond cleavage of metal-hydroperoxo complexes to form
      high-valent metal-oxo oxidants. Because these mononuclear metal-dioxygen (M-O(2))
      adducts are implicated as key intermediates in dioxygen activation reactions
      catalyzed by metalloenzymes, studies of the structural and spectroscopic
      properties and reactivities of synthetic biomimetic analogues of these species
      have aided our understanding of their biological chemistry. One particularly
      versatile class of biomimetic coordination complexes for studying dioxygen
      activation by metal complexes is M-O(2) complexes bearing the macrocyclic N
      tetramethylated cyclam (TMC) ligand. This Account describes the synthesis,
      structural and spectroscopic characterization, and reactivity studies of M-O(2)
      complexes bearing tetraazamacrocyclic n-TMC ligands, where M ? Cr, Mn, Fe, Co,
      and Ni and n = 12, 13, and 14, based on recent results from our laboratory. We
      have used various spectroscopic techniques, including resonance Raman and X-ray
      absorption spectroscopy, and density functional theory (DFT) calculations to
      characterize several novel metal-O(2) complexes. Notably, X-ray crystal
      structures had shown that these complexes are end-on metal-superoxo and side-on
      metal-peroxo species. The metal ions and the ring size of the macrocyclic TMC
      ligands control the geometric and electronic structures of the metal-O(2)
      complexes, resulting in the end-on metal-superoxo versus side-on metal-peroxo
      structures. Reactivity studies performed with the isolated metal-superoxo
      complexes reveal that they can conduct electrophilic reactions such as oxygen
      atom transfer and C-H bond activation of organic substrates. The metal-peroxo
      complexes are active oxidants in nucleophilic reactions, such as aldehyde
      deformylation. We also demonstrate a complete intermolecular O(2)-transfer from
      metal(III)-peroxo complexes to a Mn(II) complex. The results presented in this
      Account show the significance of metal ions and supporting ligands in tuning the
      geometric and electronic structures and reactivities of the metal-O(2)
      intermediates that are relevant in biology and in biomimetic reactions.

PMID- 22612524
TI  - A review of expression profiling of circulating microRNAs in men with prostate
      cancer.

PMID- 22612525
TI  - Sexual obsessions, compulsions, suicidality and homicidality in an adolescent
      diagnosed with bipolar disorder not otherwise specified, obsessive-compulsive
      disorder, pervasive developmental disorder not otherwise specified, and mild
      mental retardation.

PMID- 22612526
TI  - Efficacy of guanfacine extended release in the treatment of combined and
      inattentive only subtypes of attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: Extended-release guanfacine (GXR) is approved for the treatment of
      attention-deficit/hyperactivity disorder (ADHD) in children and adolescents aged
      6-17 years. This post-hoc analysis further examines the effects of GXR on
      hyperactivity-impulsivity and inattentiveness. METHOD: Data from two large double
      blind placebo-controlled pivotal trials of GXR in the treatment of ADHD were
      analyzed. Using the pooled population to provide sufficient sample size and
      associated statistical power, the impact of GXR treatment on core ADHD symptoms
      was examined by comparing ADHD Rating Scale IV (ADHD-RS-IV) total scores in the
      overall GXR and placebo groups in subjects with each of the three ADHD subtypes.
      ADHD-RS-IV Hyperactivity-Impulsivity and Inattentiveness subscale scores in the
      overall study population by randomized dose group (vs. placebo) were also
      examined. RESULTS: The full analysis set included 631 subjects aged 6-17 years
      (GXR: n=490; placebo: n=141). Among subjects with the predominantly inattentive
      subtype of ADHD, differences in least squares (LS) mean reductions from baseline
      in ADHD-RS-IV total scores were significantly greater in GXR-treated subjects
      (n=127) than in placebo-treated subjects (n=38) at treatment weeks 3 through 5
      and end point (p<=0.020). Among subjects with combined type ADHD, differences in
      LS mean ADHD-RS-IV total score reductions from baseline were significantly
      greater in the GXR group (n=354) than in the placebo group (n=100) at treatment
      weeks 1 through 5 and end point (p<=0.011). The dearth of predominantly
      hyperactive-impulsive type subjects (n=12) precluded analysis of this subgroup.
      Each randomized GXR dose group in each trial demonstrated significantly greater
      reductions from baseline in ADHD-RS-IV Hyperactivity-Impulsivity and
      Inattentiveness subscale scores than did the respective placebo group at end
      point (p<=0.05 for all). CONCLUSIONS: The results support the use of GXR in the
      treatment of core ADHD symptoms as defined in the American Psychiatric
      Association Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text
      Revision, including hyperactivity, impulsivity, and inattention.

PMID- 22612527
TI  - Integrating behavioral health services into a university health center: patient
      and provider satisfaction.
AB  - The goals of this study were to (a) describe an Integrated Behavioral Health Care
      (IBHC) program within a university health center and (b) assess provider and
      patient acceptability and satisfaction with the IBHC program, including
      behavioral health screening and clinical services of integrated behavioral health
      providers (BHPs). Fifteen providers (nine primary care providers and six nurses)
      and 79 patients (75% female, 65% Caucasian) completed program ratings in 2010.
      Providers completed an anonymous web-based questionnaire that assessed
      satisfaction with and acceptability of behavioral health screening and the IBHC
      program featuring integrated BHPs. Patients completed an anonymous web-based
      questionnaire that assessed program satisfaction and comfort with BHPs. Providers
      reported that behavioral health screening stimulated new conversations about
      behavioral health concerns, the BHPs provided clinically useful services, and
      patients benefited from the IBHC program. Patients reported satisfaction with
      behavioral health services and reported a willingness to meet again with BHPs.
      Providers and patients found the IBHC program beneficial to clinical care. Use of
      integrated BHPs can help university health centers support regular screening for
      mental and behavioral health issues. Care integration increases access to needed
      mental health treatment.

PMID- 22612528
TI  - To leave or not to leave: survival trade-offs between different migratory
      strategies in the greater flamingo.
AB  - 1. The balance between costs and benefits of migration under different
      environmental, density-dependent and individual conditions may promote a broad
      range of migratory behaviours. We studied the factors influencing first-year
      migration and subsequent fidelity or dispersal among wintering areas, and the
      survival costs of different wintering behaviours in the greater flamingo
      (Phoenicopterus roseus). 2. We analysed by multievent capture-recapture modelling
      among-site dispersal/fidelity and site-dependent survival probabilities from 22
      671 flamingos ringed in the Camargue (France) between 1977 and 2010 and resighted
      subsequently in their wintering grounds classified as France, Iberian Peninsula,
      Italy and North Africa. 3. We found that first- and second-year birds either
      resident or wintering at medium distances from their birth place, survived better
      than those wintering further afield. However, under severe winter conditions
      (extremely cold winter 1984-1985), individuals with the sedentary strategy
      suffered the highest levels of mortality. From the third winter onwards, the
      pattern of survival reversed: the long-distance wintering individuals (i.e. North
      Africa) survived better. 4. The proportion of first-year birds migrating for
      wintering was highly variable among cohorts and increased with favourable
      environmental conditions (wet years). After the first winter, birds showed high
      fidelity (>90%) to their previous wintering area and wintered preferably near
      their natal colony when they became adults (>2 years). 5. Survival estimates
      suggest that long-distance migration was costly for young and inexperienced
      individuals. Nonetheless, for adults, the most southern wintering areas seem to
      offer the most favourable local conditions for overwinter survival. 6. The higher
      availability of intermediate stopover sites during wet years may facilitate first
      year migration. Then, once they have some wintering experience, flamingos appear
      to favour the known wintering grounds. As they grow older, dispersing towards the
      vicinity of the natal colony may provide higher breeding prospects for
      individuals wintering closer to this high-quality and saturated breeding ground,
      as predicted by the arrival-time hypothesis.

PMID- 22612529
TI  - Pharmacokinetics of pioglitazone in lean and obese cats.
AB  - Pioglitazone is a thiazolidinedione insulin sensitizer that has shown efficacy in
      Type 2 diabetes and nonalcoholic fatty liver disease in humans. It may be useful
      for treatment of similar conditions in cats. The purpose of this study was to
      investigate the pharmacokinetics of pioglitazone in lean and obese cats, to
      provide a foundation for assessment of its effects on insulin sensitivity and
      lipid metabolism. Pioglitazone was administered intravenously (median 0.2 mg/kg)
      or orally (3 mg/kg) to 6 healthy lean (3.96 +/- 0.56 kg) and 6 obese (6.43 +/-
      0.48 kg) cats, in a two by two Latin Square design with a 4-week washout period.
      Blood samples were collected over 24 h, and pioglitazone concentrations were
      measured via a validated high-performance liquid chromatography assay.
      Pharmacokinetic parameters were determined using two-compartmental analysis for
      IV data and noncompartmental analysis for oral data. After oral administration,
      mean bioavailability was 55%, t(1/2) was 3.5 h, T(max) was 3.6 h, C(max) was 2131
      ng/mL, and AUC(0-infinity) was 15 556 ng/mL . h. There were no statistically
      significant differences in pharmacokinetic parameters between lean and obese cats
      following either oral or intravenous administration. Systemic exposure to
      pioglitazone in cats after a 3 mg/kg oral dose approximates that observed in
      humans with therapeutic doses.

PMID- 22612530
TI  - Speaking a foreign language and its effect on F0.
AB  - This study investigated whether speaking a foreign language affects the
      fundamental frequency (F0) of speech in 16 native Finnish and 14 native English
      subjects reading a text in Finnish and in English. The speech samples were
      analyzed for the mean and range of F0. Speaking a foreign language caused a
      change in F0 for the Finnish subjects, while the result was not as unambiguous
      for the English subjects. The change in F0 may be a result of adaptation to a
      certain pitch level in the foreign environment. Experience in using the foreign
      language did not show significant correlation to the change in F0, which suggests
      either individual differences in sensitivity to adaptation or difficulty in
      quantifying the amount of experience.

PMID- 22612531
TI  - Palladium-catalyzed desymmetrization of silacyclobutanes with alkynes:
      enantioselective synthesis of silicon-stereogenic 1-sila-2-cyclohexenes and
      mechanistic considerations.
AB  - A palladium-catalyzed enantioselective desymmetrization of silacyclobutanes with
      alkynes has been developed to give silicon-stereogenic 1-sila-2-cyclohexenes with
      high enantioselectivity. The products thus obtained undergo further
      derivatizations with complete stereoselectivity, and a new catalytic cycle
      involving alkyne coordination (oxidative cyclization)-transmetalation (sigma-bond
      metathesis)-reductive elimination has also been proposed.

PMID- 22612532
TI  - Healthcare personnel's experiences of situations in municipal elderly care that
      generate troubled conscience.
AB  - Healthcare personnel may perceive troubled conscience when feeling inadequate and
      powerless. It is important to further explore healthcare personnel's descriptions
      of situations in daily work, which generate troubled conscience to increase the
      awareness of such situations. This study aimed to describe health care
      personnel's experiences of situations in municipal elderly care that generate
      troubled conscience. In this qualitative study, interviews were conducted with
      Registered and Enrolled nurses and nursing assistants (n = 20) working in
      municipal elderly care. The interviews were tape-recorded, transcribed verbatim
      and analysed with content analysis. Situations that generated troubled conscience
      was (i) Being caught between different demands, comprising being forced to
      prioritize between different residents' needs, being torn between residents'
      /relatives'-/and co-workers' needs and expectations' and between work and private
      life, (ii) Being torn away from residents to other 'must do's', comprising
      stealing time from residents' to do housekeeping chore' and to 'obey' rules and
      recommendations, (iii) Feeling unable to relieve suffering, comprising falling
      short when striving to help, lacking knowledge, advice and support and time to
      ease residents' suffering and finally, (iv) Being part of providing care that is
      or feels wrong, comprising providing poor care and/or witnessing co-workers
      providing poor care, and being forced to give care that feels wrong. These
      findings identify important factors that generate stress of conscience (stress
      caused by troubled conscience), including difficulties with balancing priorities
      and following rules and recommendations that seem contrary to best care, and the
      need for interdisciplinary teamwork. Findings point to that sharing what
      conscience tells in the work team opens up possibilities for healthcare personnel
      to constructively deal with troubled conscience. Intervention studies are needed
      to explore whether such measures contribute to relieve the burden of troubled
      conscience and increase possibilities to provide high quality care.

PMID- 22612533
TI  - The absence of somatotroph proliferation during continuous stress is a result of
      the lack of extracellular signal-regulated kinase 1/2 activation.
AB  - The integrity of homeostasis can be affected by chronic stress, and
      hyposomatotropism is evident in chronic stress-associated illnesses. In the
      present study, we demonstrated that a continuous stress (CS) severely affected
      somatotrophs among hormone-secreting cells in the anterior lobe (AL) of the
      pituitary by using a rat CS model. Among AL cells, the proliferation of
      somatotrophs was almost entirely suppressed in rats that had 3-5 days of CS
      (5dCS), although other hormone-secreting cells continued to proliferate. The cell
      size of somatotrophs was reduced at 5dCS (P<0.01), the number of secretory
      granules was increased at 3dCS (P<0.01) and serum growth hormone (GH) was on
      declining trend during 1 to 5dCS, suggesting that GH release was inhibited. GH
      releasing hormone (GHRH) mRNA level in the arcuate nucleus was transiently
      decreased, whereas its receptor expression in the AL was significantly increased
      in CS rats. When 5dCS rats were injected with GHRH, transient GH secretion was
      observed, whereas proliferation of somatotrophs did not occur. The GHRH
      administration failed to stimulate extracellular signal-regulated kinase (ERK)
      1/2 phosphorylation and the nuclear translocation of ERK in somatotrophs. These
      results suggest that somatotrophs of 5dCS rats expressed sufficient GHRH
      receptor, which could transfer a signal for GH release. However, the GHRH-induced
      proliferation signal was blocked somewhere between the receptor and ERK1/2.
      Because significant increase of corticosterone in the initial stage (the 1-3dCS)
      was observed in this model, the corticosterone may affect the signalling.
      Although the mechanism underlying the blockage of the proliferation signal in
      somatotrophs under CS remains unclear, these somatotrophic disorder, suggesting
      that the present animal model may be useful for understanding the molecular
      mechanisms of chronic stress-associated illnesses.

PMID- 22612534
TI  - Lack of red hair phenotype in a North-African obese child homozygous for a novel
      POMC null mutation: nonsense-mediated decay RNA evaluation and hair pigment
      chemical analysis.

PMID- 22612535
TI  - Palladium-catalyzed aerobic oxidative cyclization of N-aryl imines: indole
      synthesis from anilines and ketones.
AB  - We report here an operationally simple, palladium-catalyzed cyclization reaction
      of N-aryl imines, affording indoles via the oxidative linkage of two C-H bonds
      under mild conditions using molecular oxygen as the sole oxidant. The process
      allows quick and atom-economical assembly of indole rings from inexpensive and
      readily available anilines and ketones and tolerates a broad range of functional
      groups.

PMID- 22612536
TI  - Dermatologic workforce on the Texas border: using burden on primary care as an
      outcome measure.

PMID- 22612537
TI  - Modifying T-cell trafficking to the intestinal as a potential management for
      inflammatory bowel disease.
AB  - INTRODUCTION: The Inflammatory Bowel Diseases (IBDs) are life-long chronic
      relapsing incurable inflammatory conditions that usually appear in the first few
      decades of life. There have been marked advances in the management of these
      conditions, but none of the currently available therapies are a panacea as they
      are neither universally efficacious nor will their efficacy necessarily last.
      There is a desperate need for new therapies that target the immunological
      deficits within the immune system with low side effects and long-term efficacy.
      AREAS COVERED: Leukocyte trafficking into the intestinal mucosa is central to the
      inflammatory pathogenesis in both Crohn's disease (CD) and ulcerative colitis
      (UC) and modification of this trafficking has the ability to reduce the level of
      inflammation. The alpha4beta7 integrin heterodimer is highly expressed on the
      CD4(+)CD45RA-memory T-cell subpopulation located within the intestine, and these
      play a critical part in the pathogenesis of IBD. EXPERT OPINION: By modifying the
      integrin and chemokine interactions with their specific receptors, inhibition of
      alpha4(+) and alpha4beta7(+) T-cell trafficking to the sites of intestinal
      inflammation is possible with promising outcomes in the management of IBD.

PMID- 22612538
TI  - Asymmetric syntheses of 1-deoxy-6,8a-di-epi-castanospermine and 1-deoxy-6-epi
      castanospermine.
AB  - Asymmetric syntheses of both 1-deoxy-6,8a-di-epi-castanospermine and 1-deoxy-6
      epi-castanospermine, polyhydroxylated indolizidine alkaloids that act as
      selective glycosidase inhibitors, have been accomplished in seven steps. The key
      feature of our unique syntheses includes the stereoselective introduction of the
      C-3 and C-4 hydroxyl groups utilizing the aza-Claisen rearrangement-induced ring
      expansion of 1-acyl-2-alkoxyvinyl pyrrolidine and a substrate-controlled
      stereoselective transannulation of the resulting azoninone intermediate.

PMID- 22612539
TI  - Long-term genetic monitoring reveals contrasting changes in the genetic
      composition of newly established populations of the intertidal snail Bembicium
      vittatum.
AB  - Newly established populations are susceptible to founder events that reduce
      genetic variation. This may be counterbalanced by gene flow after populations
      become established or founders coming from genetically different populations.
      However, initial gains in genetic diversity may be short-lived if there is
      limited mixing between lineages and subsequent inbreeding, or if one lineage
      sweeps to fixation through selection or genetic drift. Here, we report on the
      genetic changes taking place within two newly established populations of
      intertidal snail over a 15-year period (~ 10 generations). Each translocation was
      set up using multiple, genetically distinct source populations. Our data show
      that higher levels of variation in the translocated populations compared to the
      source populations were maintained over time for both nuclear (microsatellite)
      and mitochondrial genes. Small changes in allele and haplotype frequencies were
      observed in the source populations and in one of the translocated populations,
      but marked changes were evident in the other, where there was a dramatic shift
      towards the genetic make-up of one of the source populations. These genetic
      changes occurred despite relatively large numbers of founders (200-374 adults)
      and no evidence of the population experiencing a severe reduction in effective
      population size. Our study shows that the genetic composition of newly
      established populations can vary greatly over time and that genetic outcomes can
      be highly variable, and significantly different from initial expectations, even
      when they are established using high numbers of individuals and involve source
      populations from the same geographic regions.

PMID- 22612540
TI  - Amount of hemorrhage during vaginal delivery correlates with length from
      placental edge to external os in cases with low-lying placenta whose length
      between placental edge and internal os was 1-2 cm.
AB  - AIM: The aim of the present study was to investigate whether amount of hemorrhage
      during a vaginal delivery associates with the cervical length, length from the
      placental edge to the os and the sum of the two in cases with a low-lying
      placenta. MATERIAL AND METHODS: A retrospective study was performed on cases with
      low-lying placenta diagnosed at 35-36 weeks of gestation based on a distance of 1
      2 cm from the lower placental edge to the internal os, and subject to the trial
      of labor. The total amount of intrapartum hemorrhage in association with the
      distance from the placental lowest edge to the internal os (placenta-internal os
      distance, A); cervical length, B; and sum of the two (placenta-external os
      distance; A + B) were reviewed from our medical records. RESULTS: Twenty-three
      cases of low-lying placenta that underwent trial of labor were analyzed. Twenty
      (87%) of 23 patients with low-lying placenta delivered transvaginally and
      patients underwent emergency cesarean section due to intrapartum bleeding. The
      length from the placental edge to the external os (length from placental edge to
      internal os + cervical length) was correlated significantly with the total amount
      of hemorrhage during delivery (r = -0.598, P = 0.004), though neither the length
      from the placental edge to the internal os nor the cervical lengths correlated
      with it. CONCLUSION: Our results suggest that the length from the placental
      lowest edge to the external os negatively correlated with the amount of
      hemorrhage during vaginal delivery, but did not correlate with cervical length
      and distance from the placental edge to the internal os.

PMID- 22612541
TI  - Identification and quantification, by HPLC-DAD-MS/MS, of carotenoids and phenolic
      compounds from the Amazonian fruit Caryocar villosum.
AB  - The Amazonian region from Brazil has a wide variety of native and wild
      noncommercially cultivated fruits. This article reports for the first time the
      composition of carotenoids and phenolic compounds from Caryocar villosum fruit
      pulp, and, in addition, its proximate composition and antioxidant capacity (ORAC
      assay) were determined. According to the nutritional composition, water (52%) and
      lipids (25%) were the major components found in the pulp, and the total energetic
      value was 291 kcal/100 g. The major phenolic compounds identified by HPLC-DAD-ESI
      MS/MS were gallic acid (182.4 MUg/g pulp), followed by ellagic acid rhamnoside
      (107 MUg/g pulp) and ellagic acid (104 MUg/g pulp). The main carotenoids
      identified by HPLC-DAD-APCI-MS/MS were all-trans-antheraxanthin (3.4 MUg/g pulp),
      all-trans-zeaxanthin (2.9 MUg/g pulp), and a lutein-like carotenoid (2.8 MUg/g
      pulp). The antioxidant capacity of the pulp (3.7 mMol Trolox/100 g pulp)
      indicates that it can be considered a good peroxyl radical scavenger. 

PMID- 22612542
TI  - Investigation of the impact of feeding Lactobacillus plantarum CRL 1815
      encapsulated in microbially derived polymers on the rat faecal microbiota.
AB  - AIMS: The aim of this study was to evaluate the impact of the administration of
      microencapsulated Lactobacillus plantarum CRL 1815 with two combinations of
      microbially derived polysaccharides, xanthan : gellan gum (1%:0.75%) and jamilan
      : gellan gum (1%:1%), on the rat faecal microbiota. METHODS AND RESULTS: A 10-day
      feeding study was performed for each polymer combination in groups of 16 rats fed
      either with placebo capsules, free or encapsulated Lact. plantarum or water. The
      composition of the faecal microbiota was analysed by fluorescence in situ
      hybridization and temporal temperature gradient gel electrophoresis. Degradation
      of placebo capsules was detected, with increased levels of polysaccharide
      degrading bacteria. Xanthan : gellan gum capsules were shown to reduce the
      Bifidobacterium population and increase the Clostridium histolyticum group
      levels, but not jamilan : gellan gum capsules. Only after administration of
      jamilan : gellan gum-probiotic capsules was detected a significant increase in
      Lactobacillus-Enterococcus group levels compared to controls (capsules and
      probiotic) as well as two bands were identified as Lact. plantarum in two
      profiles of ileum samples. CONCLUSIONS: Exopolysaccharides constitute an
      interesting approach for colon-targeted delivery of probiotics, where jamilan :
      gellan gum capsules present better biocompatibility and promising results as a
      probiotic carrier. SIGNIFICANCE AND IMPACT OF STUDY: This study introduces and
      highlights the importance of biological compatibility in the encapsulating
      material election, as they can modulate the gut microbiota by themselves, and the
      use of bacterial exopolysaccharides as a powerful source of new targeted-delivery
      coating material.

PMID- 22612544
TI  - Short-term memory in young adults with spastic diplegic cerebral palsy.
AB  - We examined short-term memory activation processes and task-relevant, task
      irrelevant, and dynamic inhibitory processes in a group of young adults with
      hypoxic-ischaemic prenatal spastic diplegic cerebral palsy (HI-CP, N=27) with
      group-level and person-oriented methods of data analysis. Performance was
      compared with age, sex, and education of a matched control group (N=135). We
      found that HI-CP is accompanied with low level of correct answers and high levels
      of task-relevant and task-irrelevant intrusions and repetitions on the Memory
      with Pause and Homogeneous Interference short-term memory tasks. Person-oriented
      analyses revealed several different configurations of dysfunction in the HI-CP
      group.

PMID- 22612543
TI  - Reading and a diffusion model analysis of reaction time.
AB  - Processing speed is associated with reading performance. However, the literature
      is not clear either on the definition of processing speed or on why and how it
      contributes to reading performance. In this study we demonstrated that processing
      speed, as measured by reaction time, is not a unitary construct. Using the
      diffusion model of two-choice reaction time, we assessed processing speed in a
      series of same-different reaction time tasks for letter and number strings. We
      demonstrated that the association between reaction time and reading performance
      is driven by processing speed for reading-related information, but not motor or
      sensory encoding speed.

PMID- 22612545
TI  - Clinical utility of the Tower of London--Drexel University, Second Edition
      (TOLDX) after adolescent traumatic brain injury.
AB  - The performance of 43 adolescents with traumatic brain injury was evaluated on
      the Tower of London-Drexel University, second edition (TOLDX; Culbertson &
      Zillmer, 2005), and compared to that of 43 demographically matched healthy
      controls. TOLDX variables had a classification accuracy of 69.77%, with clinical
      patients demonstrating deficits in pre-planning of a schema as well as keeping
      subgoals in spatial working memory during execution. Time to follow commands and
      diffuse lesions on neuroimaging accounted for moderate amounts of variance in
      TOLDX variables. The findings support the clinical utility of the TOLDX in the
      assessment of adolescents with traumatic brain injury.

PMID- 22612546
TI  - Cognitive control and conflict adaptation similarities in children and adults.
AB  - Conflict adaptation effects occur when previous-trial congruency affects current
      trial performance. We examined developmental differences in response time (RT),
      error rate, and electrophysiological (N450 and conflict slow-potential [conflict
      SP] event-related potentials [ERPs]) indices of conflict adaptation in 21
      typically developing children and 26 adults during a Stroop task. Children
      exhibited significantly slower RTs, increased error rates, and increased ERP
      amplitudes relative to adults. Groups did not differ in magnitude of conflict
      adaptation for RTs, error rates, or the conflict SP. Neither group showed
      significant N450 conflict adaptation. Results suggest current indices of conflict
      adaptation do not differ between children and adults.

PMID- 22612547
TI  - Developmental trajectories of neural mechanisms supporting conflict and error
      processing in middle childhood.
AB  - To study age-related changes in cognitive control, event-related potentials
      (ERPs) of children aged 6-9 years, 10-12 years, and young adults were recorded
      during a Flanker task. Younger children were more susceptible to conflict than
      older ones and adults. The N2 in incongruent trials was smaller in younger than
      older children, who did not differ from adults. The error-related negativity
      (ERN) following errors, however, was larger in adults than in children, but did
      not differ between younger and older children. Delayed development of neural
      responses to error processing relative to conflict monitoring may indicate
      dissociable maturational time tables of subdivisions of the anterior cingulate
      cortex.

PMID- 22612548
TI  - Concentration of antioxidant polyphenols from Thymus capitatus extracts by
      membrane process technology.
AB  - Thymus capitatus is a Mediterranean plant characterized by its antioxidant
      polyphenols of which the most known are the carnosic and rosmarinic acids. In
      this way, this study aims to concentrate these acids by membrane processes. The
      thyme essential oil composition was established by capillary GC-MS and 27
      components were identified representing 98.93%+/- 1.97% of total oils. The
      antioxidant test for permeate and retentate of methanolic and aqueous extract
      were determined using 3 types of membranes. The results showed that the synthetic
      NF membrane is able to trap and concentrate phenolic compounds in the retentate
      much better than the NF commercial and UF synthetic membrane. The results of the
      total phenolic content (TPC) showed a significant value of the polyphenol content
      present in the aqueous extract with 175.53 mg Gallic Acid Equivalents (GAE)/g of
      extract. The spectrum of the aqueous extract of Thymus capitatus showed the
      presence of 3 visible peaks, the 1st one at 217 nm corresponding to the carnosic
      acid, the 2nd one at 277 nm for essential oils, and the last one at 326 nm
      attributed to the rosmarinic acid. The commercial membrane NF-DK succeeded to
      concentrate rosmarinic acid and can be considered as a stage towards the
      concentration of this product with a high added value.

PMID- 22612549
TI  - Solution-phase synthesis of a highly substituted furan library.
AB  - A library of furans has been synthesized by iodocyclization and further
      diversified by palladium-catalyzed coupling processes. The key intermediate 3
      iodofurans have been prepared by the electrophilic iodocyclization of 2-iodo-2
      alken-1-ones in the presence of various nucleophiles in good to excellent yields
      under mild reaction conditions. These 3-iodofurans are the key components for
      library generation through subsequent elaboration by palladium-catalyzed
      processes, such as Suzuki-Miyaura, Sonagashira, Heck, aminocarbonylation, and
      carboalkoxylation chemistry to afford a diverse set of 2,3,4,5-tetrasubstituted
      furans. 

PMID- 22612550
TI  - Impact of bottled water storage duration and location on bacteriological quality.
AB  - An investigation studying the effects of storage duration and location on the
      persistence of heterotrophic microorganisms in oligotrophic bottled water
      environments has been completed. One-gallon high-density polyethylene water
      containers stored for up to 16 weeks at temperatures ranging from 2 degrees C to
      >49 degrees C in a refrigerator, indoor cabinet, covered porch, and car trunk
      were evaluated for microbiological quality. Heterotrophic plate counts (HPCs) of
      up to 4 * 10(3) cfu/mL were detected in containers stored on a porch and car
      trunk; whereas, HPCs were found not to exceed 400 cfu/mL and 100 cfu/mL for
      bottles stored in indoor cabinets and refrigerators, respectively. Containers
      stored on an enclosed porch for up to seven years contained HPC of up to 4 *
      10(4) cfu/mL. Logistic and Gompertz growth models predicted microbial growth
      rates for bottled water stored on a protected porch environment for long (R(2)
      0.99) and short-term (R(2) 0.86) durations.

PMID- 22612551
TI  - Satoyoshi syndrome: a cause of alopecia universalis in association with
      neurologic and bony abnormalities.
AB  - Satoyoshi syndrome is a rare multisystemic disorder characterized by alopecia,
      diarrhea, muscle spasms, osseous abnormalities, and endocrinopathies. We report a
      case of Satoyoshi syndrome misdiagnosed as vitamin D-dependent rickets for
      several years.

PMID- 22612552
TI  - Preparation and in vitro release of zein microparticles loaded with prednisolone
      for oral delivery.
AB  - Zein has been proposed as a polymer for targeted-drug delivery via the oral
      route. Zein microparticles were loaded with prednisolone and evaluated as an oral
      delivery system. Microparticles were formulated using phase separation. Starting
      quantities of zein and prednisolone, along with the agitation method and
      temperature were found to significantly impact drug loading and loading
      efficiency. Vortex mixing produced the highest drug loading and loading
      efficiency. Drug release was measured in simulated conditions of the stomach and
      small intestine using the microparticles made with the method that best improved
      drug loading. In simulated stomach and small intestine conditions, prednisolone
      release reached almost 70% over 3 and 4 h, respectively. While a clinically
      relevant dose may be delivered using c. 100 mg of zein microparticles,
      prednisolone release from the microparticles indicates that they may not be
      suited as a controlled- or targeted-delivery system.

PMID- 22612553
TI  - Effects of extrusion, lipid concentration and purity on physico-chemical and
      biological properties of cationic liposomes for gene vaccine applications.
AB  - We developed cationic liposomes containing DNA through a conventional process
      involving steps of (i) preformation of liposomes, (ii) extrusion, (iii) drying
      and rehydration and (iv) DNA complexation. Owing to its high prophylactic
      potentiality against tuberculosis, which had already been demonstrated in
      preclinical assays, we introduced modifications into the conventional process
      towards getting a simpler and more economical process for further scale-up.
      Elimination of the extrusion step, increasing the lipid concentration (from 16 to
      64 mM) of the preformed liposomes and using good manufacturing practice bulk
      lipids (96-98% purity) instead of analytical grade purity lipids (99.9-100%) were
      the modifications studied. The differences in the physico-chemical properties,
      such as average diameter, zeta potential, melting point and morphology of the
      liposomes prepared through the modified process, were not as significant for the
      biological properties, such as DNA loading on the cationic liposomes, and
      effective immune response in mice after immunisation as the control liposomes
      prepared through the conventional process. Beneficially, the modified process
      increased productivity by 22% and reduced the cost of raw material by 75%.

PMID- 22612554
TI  - Chitosan scaffolds with BMP-6 loaded alginate microspheres for periodontal tissue
      engineering.
AB  - The aim of this study is to develop an effective growth factor releasing scaffold
      microsphere system for promoting periodontal tissue engineering. Bone
      morphogenetic protein-6 (BMP-6)-loaded alginate microspheres in narrow size
      distribution were produced by optimising electrospraying conditions. The addition
      of these microspheres to chitosan gels produced a novel scaffold in which not
      only the pore sizes and interconnectivity were preserved, but also a controlled
      release vehicle was generated. Loading capacity was adjusted as 50 ng or 100 ng
      BMP-6 for each scaffold and the controlled release behaviour of BMP-6 from
      chitosan scaffolds was observed during seven days. Cell culture studies were
      carried out with rat mesenchymal stem cells derived from bone marrow in three
      groups; chitosan scaffolds, chitosan scaffolds containing BMP-6-loaded alginate
      microspheres and chitosan scaffolds with free BMP-6 in culture medium. Results
      showed that controlled delivery of BMP-6 from alginate microspheres has a
      significant effect on osteogenic differentiation.

PMID- 22612555
TI  - Incomplete thermal ablation stimulates proliferation of residual renal carcinoma
      cells in a translational murine model.
AB  - What's known on the subject? and What does the study add? Thermal ablation
      influences the local tissue microenvironment. Several studies have reported that
      residual tumour cells may exhibit a more aggressive phenotype. This study shows
      that incomplete CA and RFA cause an increased proliferation and decreased
      apptosis of residual renal tumour cells. This may be caused by stimulatory
      factors such as hypoxia, HSPs and inflammatory cells. OBJECTIVE: To compare the
      effect of incomplete thermal ablation vs partial nephrectomy (PN) on growth
      stimulation and cellular survival in renal tumours. MATERIALS AND METHODS: Renca
      renal tumours were transplanted under the renal capsule of mice (four to six
      mice/group) after which incomplete radiofrequency ablation (RFA), cryoablation
      (CA) or PN was performed. At several time points after treatment, presence of
      cell proliferation, apoptosis, hypoxic areas, inflammatory factors and the heat
      shock proteins (HSPs) 70 and 90 were evaluated using immunohistochemistry.
      RESULTS: At 2 h after thermal ablation residual tumour cells showed increased
      proliferation. This hyperproliferation was significantly stronger after RFA than
      CA (P < 0.05) and not present after PN. Residual cells showed increased apoptosis
      after 2 h and decreased apoptosis from 2 days after thermal ablation. Apoptotic
      cells were significantly less evident at 3 days after RFA (P < 0.001). Hypoxic
      areas and HSPs were increasingly present from 2 h up to 7 days after thermal
      ablation (P < 0.001). Inflammatory cells infiltrated mainly the necrotic areas
      after thermal ablation, and their abundance peaked at 1 week after ablation (P <
      0.05). The increased cell growth was preceded by hypoxia and presence of HSPs.
      CONCLUSIONS: CA and RFA result in an increased proliferation and decreased
      apoptosis of residual renal tumour cells. This hyperproliferation may be caused
      by stimulatory factors, e.g. hypoxia, HSPs and inflammatory cells, and could
      facilitate recurrences of renal tumours after thermal ablation. This study
      highlights the importance of achieving complete tumour destruction.

PMID- 22612557
TI  - Social cognitive mediators of the effect of the MobileMums intervention on
      physical activity.
AB  - OBJECTIVE: To explore whether improvements in physical activity following the
      MobileMums intervention were mediated by changes in Social Cognitive Theory (SCT)
      constructs targeted in the intervention (barrier self efficacy, goal setting
      skills, outcome expectancy, social support, and perceived environmental
      opportunity for exercise). This paper also examined if the mediating constructs
      differed between initial (baseline to 6 weeks) and overall (baseline to 13 weeks)
      changes in physical activity. METHODS: Secondary analysis of data from a
      randomized controlled trial involving 88 postnatal women (<12 months postpartum).
      Participants were randomized to receive either the 12-week MobileMums
      intervention or a minimal-contact control condition. Physical activity and
      proposed mediators were assessed by self-report at baseline, 6 weeks, and 13
      weeks. Walking for Exercise frequency was assessed using the Australian Women's
      Activity Survey and frequency of moderate-to-vigorous physical activity (MVPA)
      was assessed using a single-item question. RESULTS: Initial improvements in goal
      setting skills mediated the relationship between experimental condition and
      initial changes in MVPA, alphabeta (95% CI) = 0.23(0.01, 0.59), and Walking for
      Exercise, alphabeta (95% CI) = 0.34(0.06, 0.73). Initial improvements in barrier
      self efficacy mediated the relationship between experimental condition and
      initial change in MVPA, alphabeta (95% CI) = 0.36(0.12, 0.65), but not Walking
      for Exercise. None of the SCT outcomes significantly mediated the relationship
      between experimental condition and overall (baseline to 13 weeks) change in
      frequency of MVPA or Walking for Exercise. CONCLUSION: Future interventions with
      postnatal women using SCT should target barrier self-efficacy and goal setting
      skills in order to increase physical activity.

PMID- 22612556
TI  - Impact of ion binding on poly-L-lysine (un)folding energy landscape and kinetics.
AB  - We utilize T-jump UV resonance Raman spectroscopy (UVRR) to study the impact of
      ion binding on the equilibrium energy landscape and on (un)folding kinetics of
      poly-L-lysine (PLL). We observe that the relaxation rates of the folded
      conformations (including pi-helix (bulge), pure alpha-helix, and turns) of PLL
      are slower than those of short alanine-based peptides. The PLL pure alpha-helix
      folding time is similar to that of short alanine-based peptides. We for the first
      time have directly observed that turn conformations are alpha-helix and pi-helix
      (bulge) unfolding intermediates. ClO(4)(-) binding to the Lys side chain 
      NH(3)(+) groups and the peptide backbone slows the alpha-helix unfolding rate
      compared to that in pure water, but little impacts the folding rate, resulting in
      an increased alpha-helix stability. ClO(4)(-) binding significantly increases the
      PLL unfolding activation barrier but little impacts the folding barrier. Thus,
      the PLL folding coordinate(s) differs from the unfolding coordinate(s). The-pi
      helix (bulge) unfolding and folding coordinates do not directly go through the
      alpha-helix energy well. Our results clearly demonstrate that PLL (un)folding is
      not a two-state process.

PMID- 22612558
TI  - Age-related patterns in negative affect and appraisals about colorectal cancer
      over time.
AB  - OBJECTIVE: Age differences in reactions to cancer are established but poorly
      understood. The purpose of this study was to apply the theoretical model of
      strength and vulnerability integration (SAVI; Charles, 2010) to understand age
      related patterns in emotional experiences and cancer appraisals among people
      diagnosed with colorectal cancer. METHODS: Individuals recently diagnosed with
      colorectal cancer (N = 139; 28-89 years-old) completed measures of positive and
      negative affect, depressive symptoms, and appraisals about cancer at four time
      points: baseline (prior to colorectal cancer surgery), 6-, 12-, and 18-months
      postsurgery. Multilevel modeling examined changes in affective experience and
      appraisals over time, across age, and the interaction of time by age. RESULTS:
      Negative affect decreased more rapidly over time among older adults than younger
      adults, p < .05, but positive affect was reasonably stable and unrelated to age.
      Depressive symptoms were also fairly stable over time, but consistently higher
      among younger adults, p < .01. Older age was significantly related to lower
      threat appraisals and greater levels of challenge, p < .01. Threat, but not
      challenge, mediated the age-by-time interaction predicting negative affect.
      CONCLUSIONS: Older age was related to lower levels of depressive symptoms and
      negative affect. Older adults also reported more adaptive appraisals of their
      cancer, which accounted for their more rapid decline in negative affect compared
      to younger adults. Overall, SAVI is a useful model for understanding age-related
      patterns in emotional well-being and appraisals in the context of colorectal
      cancer.

PMID- 22612559
TI  - Some feelings are more important: cognitive attitudes, affective attitudes,
      anticipated affect, and blood donation.
AB  - OBJECTIVE: The present research assessed the simultaneous effects of four
      attitude variables (cognitive attitudes, affective attitudes, anticipated
      negative affective reactions, and anticipated positive affective reactions) in
      the context of the theory of planned behavior (TPB) on blood-donation intentions
      and behavior. METHODS: Experienced blood donors (N = 1108) completed
      questionnaires measuring attitude variables plus components of the TPB and a
      measure of attitudinal ambivalence in relation to giving blood again in the next
      six months. Records were used to assess whether participants subsequently donated
      blood again in the six months after completing the questionnaire. The main
      outcome measures were objectively assessed blood donation and intentions to make
      an additional donation of blood. RESULTS: Confirmatory factor analysis supported
      a distinction between cognitive attitudes about giving blood, affective attitudes
      about giving blood, anticipated negative affective reactions about not giving
      blood, and anticipated positive affective reactions about giving blood. Multiple
      regression analyses indicated that perceived behavioral control, anticipated
      negative affective reactions, cognitive attitude, anticipated positive affective
      reactions and subjective norms were significant simultaneous predictors of
      intentions to donate blood. Logistic regression analyses indicated that
      intentions, perceived behavioral control, and anticipated positive affective
      reactions were significant, simultaneous predictors of blood donation.
      Attitudinal ambivalence significantly moderated the effects of cognitive
      attitudes on intentions, and the effects of anticipated negative affective
      reactions on both intentions and donation behavior. CONCLUSION: The findings
      point to the value of considering different types of attitudes, and anticipated
      negative affective reaction in particular, for predicting health behaviors.

PMID- 22612560
TI  - Evaluative conditioning makes slim models less desirable as standards for
      comparison and increases body satisfaction.
AB  - OBJECTIVE: The present research tested whether an evaluative conditioning
      intervention makes thin-ideal models less enviable as standards for appearance
      based social comparisons (Study 1), and increases body satisfaction (Study 2).
      DESIGN: Female participants were randomly assigned to intervention versus control
      conditions in both studies (ns = 66 and 39). Intervention participants learned to
      associate thin-ideal models with synonyms of fake whereas control participants
      completed an equivalent task that did not involve learning this association. MAIN
      OUTCOME MEASURES: The dependent variable in Study 1 was an implicit measure of
      idealization of slim models assessed via a modified Implicit Association Test
      (IAT). Study 2 used a validated, self-report measure of body satisfaction as the
      outcome variable. RESULTS: Intervention participants showed significantly less
      implicit idealization of slim models on the IAT compared to controls (Study 1).
      In Study 2, participants who undertook the intervention exhibited an increase in
      body satisfaction scores whereas no such increase was observed for control
      participants. CONCLUSION: The present research indicates that it is possible to
      overcome the characteristic impact of thin-ideal models on women's judgments of
      their bodies. An evaluative conditioning intervention made it less likely that
      slim models were perceived as targets to be emulated, and enhanced body
      satisfaction.

PMID- 22612561
TI  - Synthesis of 1,2-disubstituted cyclopentenes by palladium-catalyzed reaction of
      homopropargyl-substituted dicarbonyl compounds with organic halides via 5-endo
      dig cyclization.
AB  - Palladium catalysts with bulky biaryl phosphine ligands allow homopropargyl
      substituted dicarbonyl compounds to undergo intramolecular addition via a rare 5
      endo-dig pathway. C-C bond forming reductive elimination follows the addition to
      introduce alkenyl and alkynyl as well as aryl groups by using the corresponding
      organic halides. The cyclization is versatile enough to be applicable to the
      synthesis of highly substituted dihydropyrrole and a fused tricyclic compound.

PMID- 22612562
TI  - Leucine improves glucose and lipid status in offspring from obese dams, dependent
      on diet type, but not caloric intake.
AB  - Previously, we showed that offspring from obese rat dams were hyperphagic, with
      increased adiposity, hyperlipidaemia and glucose intolerance associated with
      increased orexigenic neuropeptide expression after fasting. Mammalian target of
      rapamycin (mTOR) can inhibit food intake through a hypothalamic action. As we
      previously showed that maternal obesity down-regulated hypothalamic mTOR, in the
      present study, we hypothesised that dietary leucine supplementation would
      activate hypothalamic mTOR to reduce food intake, thus limiting metabolic
      disorders in offspring from obese dams, regardless of postweaning diet. Obesity
      was induced in Sprague-Dawley females by high-fat diet (HFD) for 5 weeks before
      mating, throughout gestation and lactation. Male pups from HFD-fed mothers were
      weaned onto chow or HFD; within each dietary group, half were supplied with
      leucine via drinking water (1.5%) versus water control for 10 weeks. Those from
      chow-fed mothers were fed chow and water. Maternal obesity led to increased
      adiposity in chow-fed offspring. Postweaning HFD consumption exaggerated
      adiposity, hyperglycaemia, hyperinsulinaemia and hyperlipidaemia. Supplementation
      with leucine doubled leucine intake and increased hypothalamic mTOR activation;
      however, appetite regulation was not affected. A reduction in blood lipid levels
      was observed in offspring regardless of diet, as well as improved glucose
      tolerance in HFD-fed rats. In HFD-fed rats, up-regulated carnitine palmitoyl
      transferase-1 and peroxisome-proliferator-activated receptor-gamma coactivator
      1alpha in muscle and glucose transporter 4 in fat suggested that leucine improved
      peripheral fat oxidation and glucose transport. Leucine is able to improve
      peripheral glucose and lipid metabolism independent of appetite and weight
      regulation, suggesting its potential application in the management of metabolic
      disorders.

PMID- 22612563
TI  - A case of sarcoidosis mimicking Wegener's granulomatosis.

PMID- 22612564
TI  - 3D analysis of the morphology and spatial distribution of nitrogen in nitrogen
      doped carbon nanotubes by energy-filtered transmission electron microscopy
      tomography.
AB  - We present here the application of the energy-filtered transmission electron
      microscopy (EFTEM) in the tomographic mode to determine the precise 3D
      distribution of nitrogen within nitrogen-doped carbon nanotubes (N-CNTs). Several
      tilt series of energy-filtered images were acquired on the K ionization edges of
      carbon and nitrogen on a multiwalled N-CNT containing a high amount of nitrogen.
      Two tilt series of carbon and nitrogen 2D maps were then calculated from the
      corresponding energy-filtered images by using a proper extraction procedure of
      the chemical signals. Applying iterative reconstruction algorithms provided two
      spatially correlated C and N elemental-selective volumes, which were then
      simultaneously analyzed with the shape-sensitive reconstruction deduced from Zero
      Loss recordings. With respect to the previous findings, crucial information
      obtained by analyzing the 3D chemical maps was that, among the two different kind
      of arches formed in these nanotubes (transversal or rounded ones depending on
      their morphology), the transversal arches contain more nitrogen than do the round
      ones. In addition, a detailed analysis of the shape-sensitive volume allowed the
      observation of an unexpected change in morphology along the tube axis: close to
      the round arches (with less N), the tube is roughly cylindrical, whereas near the
      transversal ones (with more N), its shape changes to a prism. This relatively new
      technique is very powerful in the material science because it combines the
      ability of the classical electron tomography to solve 3D structures and the
      chemical selectivity of the EFTEM imaging.

PMID- 22612565
TI  - Psycho-logic: some thoughts and after-thoughts.
AB  - The main features of the system of psycho-logic and its historical origins,
      especially in the writings of Heider and Piaget, are briefly reviewed. An updated
      version of the axioms of psycho-logic, and a list of the semantic primitives of
      Wierzbicka are presented. Some foundational questions are discussed, including
      the genetically determined limitations of human knowledge, the constructive,
      moral, and political nature of the approach, the role of fortuitous events, the
      ultimate limitations of psychological knowledge (the "balloon" to be inflated
      from the inside), the role of the subjective unconscious, and the implications of
      the approach for practice.

PMID- 22612566
TI  - Systematic identification and classification of three-dimensional activity
      cliffs.
AB  - Activity cliffs were systematically extracted from public domain X-ray structures
      of targets for which complexes with multiple ligands were available, following
      the concept of three-dimensional (3D) cliffs. Binding modes of ligands with well
      defined potency measurements were compared in a pairwise manner, and their 3D
      similarity was calculated using a previously reported property density function
      based method taking conformational, positional, and chemical differences into
      account. Requiring the presence of at least 80% 3D similarity and a potency
      difference of at least 2 orders of magnitude as cliff criteria, a total of 216
      well-defined 3D activity cliffs were detected in the Protein Data Bank (PDB).
      These 3D-cliffs involved a total of 269 ligands active against 38 different
      targets belonging to 17 protein families. For 255 of these compounds, binding
      modes were available at high crystallographic resolution. All 3D-cliffs were
      analyzed in detail and assigned to different categories on the basis of
      crystallographic interaction patterns. In many instances, differences in ligand
      target interactions suggested plausible causes for origins of 3D-cliffs. In other
      cases, short-range interactions seen in X-ray structures were insufficient to
      deduce possible reasons for cliff formation. The 3D-cliffs described herein
      further advance the rationalization of activity cliffs at the level of ligand
      target interactions and should also be useful for other applications such as the
      calibration of energy functions for structure-based design. The pool of
      identified activity cliffs is provided to enable subsequent structure-based
      analyses of cliffs.

PMID- 22612567
TI  - Hybrid septate uterus, coexistence of bicornuate and septate varieties: a genuine
      report.
AB  - AIM: To highlight the coexistence of a uterine septum in cases diagnosed as
      bicornuate uterus on the basis of the external shape of the uterine fundus and to
      present the outcomes of its hysteroscopic management. METHODS: Descriptive
      clinical report. Cases with two-chambered uterine cavities were recruited with
      exclusion of cases with pure bicornuate uteri. The differentiation between hybrid
      and pure septate uterine varieties was based on clinical evaluation, transvaginal
      ultrasonic evaluation, hysterosalpingography and in addition to bimanual
      examination under anesthesia. The final diagnosis was confirmed by combined
      hysteroscopy-laparoscopy examinations. Cases with pure and hybrid septate uteri
      were managed by hysteroscopic metroplasty and the outcomes were compared.
      RESULTS: Out of 357 cases of double chambered uteri, 18 cases (5%) were found to
      be a pure bicornuate variety (PBV), 322 (90.2%) cases were found to have pure
      septate variety (PSV) and 17 cases (4.8%) were found to have hybrid septate
      variety (HSV). In HSV, there was external fundal depression dividing only the
      upper part of the corpus giving an imprecise impression of a bicornuate uterus
      with a laparoscopic view, but there was a long extension of the dividing
      interface. Nine cases with HSV were associated with a complete utero-cervico
      vaginal septum, and five cases had a complete uterine septum. The diagnosis of
      asymmetric horns, hemi-obstruction or bicervical uterus was made in three cases
      with HSV. All cases with a septate uterus were offered hysteroscopic metroplasty,
      and cases with fundal depression were operated under laparoscopic monitoring. In
      cases with HSV, the procedure was performed safely and successfully in 16/17
      cases (94%). One uterine perforation was encountered, giving a six-fold increase
      in the perforation risk, and passed uneventfully. Successful reproductive
      outcomes were reported in 178/189 cases (94.1%) with PSV and in 12/15 (80%) with
      HSV. CONCLUSIONS: External fundal depressions of variable depths are associating
      with a septate uterus, indicating coexistence of the two anomalies. These cases
      are candidates for hysteroscopic metroplasty under appropriate sonographic and/or
      laparoscopic monitoring.

PMID- 22612568
TI  - Current status of inflammasome blockers as anti-inflammatory drugs.
AB  - INTRODUCTION: The inflammasomes have emerged as key mediators of inflammation and
      immunity, yet clinical application of this knowledge has been limited by a lack
      of specific and drug-like antagonists. Recent studies using inflammasome knockout
      mice have shown that different inflammasomes control immunity in different
      pathologies. Drug-like antagonists acting up- or down-stream of the inflammasome
      pathway have been successfully used in clinics as important therapeutics to treat
      different inflammatory diseases. AREAS COVERED: The current literature has been
      reviewed on the role of inflammasomes in inflammatory disease, focusing on
      potential therapeutic applications of selective inflammasome antagonists as anti
      inflammatory agents. Particular emphasis has been placed on the potential role of
      the different inflammasomes in common inflammatory diseases. The latest clinical
      developments for drugs targeting inflammasome pathways are covered. EXPERT
      OPINION: Recent studies using inflammasome knockout mice suggest its importance
      as a potential therapeutic target for the treatment of inflammatory disease.
      However, efficacious antagonists for the inflammasome for use in clinical studies
      are still at an early stage of development. Developing selective inflammasome
      antagonists is a challenge that if met, offers promise for the treatment of
      chronic inflammatory diseases. Major developments in this area will include the
      identification of reliable high-throughput screening methods for compounds
      directly targeting inflammasome assembly.

PMID- 22612569
TI  - Palladium-catalyzed C-H bond direct alkynylation of 5-membered heteroarenes: a
      well-defined synthetic route to azole derivatives containing two different
      alkynyl groups.
AB  - A widely applicable oxidative coupling of 5-membered heteroarenes and terminal
      alkynes that uses a combination of palladium and silver salts was developed.
      Under suitable conditions, imidazole and benzimidazole, which are sluggish under
      similar previously reported oxidative coupling conditions, as well as imidazo[1,5
      a]pyridines, oxazole, benzoxazole, thiazole, and benzothiazole could be
      alkynylated. In addition, the bromine atom on the substrates was intact under the
      reaction conditions, and conventional Sonogashira coupling did not occur at all.
      With these reactivities in hand, a well-defined synthetic route to imidazo[1,5
      a]pyridines and thiazole containing two different alkynyl groups was achieved in
      a simple manner. In addition, linear correlations were observed between the
      fluorescence wavelength and the Hammett substituent constants of aryl groups, not
      only on the C1- but also on the C3-alkynyl group of the obtained 1,3
      bis(arylethynyl)imidazo [1,5-a]pyridines.

PMID- 22612570
TI  - 'Humans and other animals'-on the scope of brain science.
AB  - Abstract: This essay is dedicated to Obaid on the occasion of his 80th birthday.
      We both worked on the behavior of Drosophila and on what underlies behavior in
      the fly brain. Is that the fly's mind? The essay is about some limitations of
      brain science. It is just a little piece of writing. It is meant to honor Obaid
      for his contributions to Drosophila neurogenetics in 40 years and to science in
      India. I hope he takes it instead of a bowl of flowers-adding to the praise.

PMID- 22612571
TI  - Overall treatment success after treatment of primary superficial basal cell
      carcinoma: a systematic review and meta-analysis of randomized and nonrandomized
      trials.
AB  - BACKGROUND: Several noninvasive treatment modalities are available for
      superficial basal cell carcinoma (sBCC). OBJECTIVES: This systematic review aims
      to determine residue, recurrence and tumour-free survival probabilities of
      patients with primary sBCC treated with the currently most frequently used
      therapies. METHODS: The PubMed (January 1946 to October 2010), EMBASE (January
      1989 to October 2010) and Cochrane (January 1993 to October 2010) databases, and
      reference lists were searched without date restriction. Inclusion criteria were
      studies that included primary, histologically proven sBCCs, that reported on
      residue and/or recurrence probabilities after treatment, and had a minimum follow
      up period of 12 weeks. Both randomized and nonrandomized studies were included.
      The primary and secondary outcomes were the probability of complete response and
      tumour-free survival, respectively. Two independent reviewers selected 36 studies
      (14 randomized and 22 nonrandomized), and extracted residue, cumulative
      recurrence and tumour-free survival probabilities. RESULTS: Pooled estimates of
      percentages of sBCC with complete response at 12 weeks post-treatment, derived
      from 28 studies, were 86.2% [95% confidence interval (CI) 82-90%] for imiquimod
      treatment, and 79.0% (95% CI 71-87%) for photodynamic therapy (PDT). With respect
      to tumour-free survival at 1 year, the pooled estimates derived from 23 studies
      were 87.3% for imiquimod (95% CI 84-91%) and 84.0% for PDT (95% CI 78-90%). Only
      a small number of studies reported on the results of sBCC treatment with 5
      fluorouracil (one), surgical excision (one) and cryotherapy (two). CONCLUSIONS:
      Pooled estimates from randomized and nonrandomized studies showed similar tumour
      free survival at 1 year for imiquimod and PDT. The PDT tumour-free survival was
      higher in studies with repeated treatments. However, these results were largely
      derived from nonrandomized studies, and randomized studies with head-to-head
      comparison of imiquimod and PDT are lacking. There is a need for head-to-head
      comparison studies between PDT, imiquimod and other treatments with long-term
      follow-up to enable better recommendations for optimal sBCC treatment.

PMID- 22612572
TI  - Pediatric segmental eccrine spiradenomas: a case report and review of the
      literature.
AB  - Eccrine spiradenoma is a rare benign adnexal tumor that usually occurs as a
      solitary nodule, although there are reports of multiple eccrine spiradenomas
      occurring in a segmental, linear, blaschkoid, or zosteriform pattern. Segmental
      eccrine spiradenomas have rarely been reported with onset occurring in childhood
      or adolescence. We describe a case of segmental eccrine spiradenomas occurring on
      the neck and mandible of a child. 

PMID- 22612573
TI  - Neuropsychological measures predict decline to Alzheimer's dementia from mild
      cognitive impairment.
AB  - OBJECTIVE: Studies of Mild Cognitive Impairment (MCI) show elevated rates of
      conversion to dementia at the group level. However, previous studies of the
      trajectory of MCI identify great heterogeneity of outcomes, with a significant
      proportion of individuals with MCI remaining stable over time, changing MCI
      subtype classification, or reverting to a normal cognitive state at long-term
      follow-up. METHOD: The present study examined individual outcomes at 20 months in
      a group of older adults classified according to MCI subtypes. A total of 106
      participants, 81 with different subtypes of MCI and 25 healthy controls,
      undertook longitudinal neuropsychological assessment of visual and verbal memory,
      attentional processing, executive functions, working memory capacity, and
      semantic memory. RESULTS: At 20 months 12.3% of the MCI group progressed to
      dementia, 62.9% continued to meet MCI criteria, and 24.7% reverted to unimpaired
      levels of function. A discriminant function analysis predicted outcome at 20
      months on the basis of baseline neuropsychological test performance with 86.3%
      accuracy. The analysis indicated that a pattern of impairments on visual episodic
      memory, verbal episodic memory, short-term memory, working memory, and
      attentional processing differentiated between participants who developed
      dementia, recovered from MCI, or remained in stable MCI. CONCLUSIONS: The results
      of the present study raise questions regarding the specificity of existing
      criteria for the subtypes of MCI, with these results indicating a high degree of
      instability in classification over time. In addition, the results suggest that
      multidomain MCI is the most reliable precursor stage to the development of AD.

PMID- 22612574
TI  - Response inhibition deficits in unaffected first-degree relatives of patients
      with borderline personality disorder.
AB  - OBJECTIVE: Impulsiveness is a heritable feature of borderline personality
      disorder (BPD) which aggregates in families affected with the illness. Whereas
      BPD patients show deficits on neuropsychological tests of response inhibition, it
      is unknown whether these deficits are also present in their first-degree
      biological relatives who are at an increased genetic risk for this illness. The
      purpose of the current study was to identify and characterize a subgroup of BPD
      patients with pronounced response inhibition deficits, and secondarily, to
      estimate the relative recurrence risk of these deficits among affected families.
      METHOD: Thirty-nine pairs of female BPD probands and their unaffected first
      degree biological sisters were recruited from hospital outpatient clinics.
      Participants completed the Conners' Continuous Performance Test (CPT) and the
      Barratt Impulsiveness Scale-11. RESULTS: BPD relatives made a similar number of
      commission errors on the CPT compared to healthy controls with no personal or
      family history of psychiatric illness; however, cluster analysis revealed a
      subgroup of BPD relatives who displayed clinically elevated commission errors and
      atypically fast RTs to target stimuli, indicating a genuine response inhibition
      deficit. The estimated relative recurrence risk for response inhibition deficits
      for all sibling pairs on the CPT was moderate at lambda = 4.55. CONCLUSIONS:
      These findings suggest that response inhibition deficits are pronounced in some
      BPD relatives, may be heritable between siblings, are nonredundant with
      diagnostic status, and show promise as candidate neuropsychological
      endophenotypes for BPD.

PMID- 22612575
TI  - Age-related differences in episodic memory: a synergistic contribution of genetic
      and physiological vascular risk factors.
AB  - OBJECTIVE: Vascular risk is associated with impairments in age-sensitive
      cognitive functions. However, age-associated differences in vascular risk and
      cognitive functioning can be explained in part by genetic factors, such as the
      presence of epsilon4 allele of the Apolipoprotein E (APOE) gene. Although the
      links between these factors and cognitive deficits are frequently reported, their
      joint impact on healthy adults is rarely investigated. We hypothesized that
      phenotypic indicators of vascular risk (increased pulse pressure and high blood
      cholesterol levels) and genetic (APOE epsilon4 allele) risk factors would exert a
      synergistic negative influence on episodic memory in healthy rather than typical
      adults. METHOD: We measured blood pressure, blood cholesterol levels, recognition
      memory, and free recall in a life span sample of normotensive adults 18-77 years
      of age. APOE genotype was determined from buccal cultures. RESULTS: A general
      linear model analysis showed that elevated pulse pressure was associated with
      poorer memory but only in the carriers of epsilon4 allele--APOE Status * PP
      interaction, F(1, 110) = 4.82, eta2(p) = .042, p = .03-whereas advanced age was
      associated with lower memory scores only in epsilon3 homozygotes: APOE Status *
      Age, F(1, 110) = 4.92, eta2(p) = .043, p = .029. CONCLUSIONS: A joint influence
      of relatively mild risk factors is associated with reduced memory performance,
      even in healthy adults.

PMID- 22612576
TI  - Authoritarianism, religious fundamentalism, and the human prefrontal cortex.
AB  - OBJECTIVE: The psychological processes of doubting and skepticism have recently
      become topics of neuroscientific investigation. In this context, we developed the
      False Tagging Theory, a neurobiological model of the belief and doubt process,
      which proposes that the prefrontal cortex is critical for normative doubt
      regarding properly comprehended cognitive representations. Here, we put our
      theory to an empirical test, hypothesizing that patients with prefrontal cortex
      damage would have a doubt deficit that would manifest as higher authoritarianism
      and religious fundamentalism. METHOD: Ten patients with bilateral damage to the
      ventromedial prefrontal cortex (vmPFC), 10 patients with damage to areas outside
      the vmPFC, and 16 medical comparison patients, who experienced life-threatening
      (but non-neurological) medical events, completed a series of scales measuring
      authoritarianism, religious fundamentalism, and specific religious beliefs.
      RESULTS: vmPFC patients reported significantly higher authoritarianism and
      religious fundamentalism than the other groups. The degrees of authoritarianism
      and religious fundamentalism in the vmPFC group were significantly higher than
      normative values, as well; by contrast, the comparison groups did not differ from
      normative values. Moreover, vmPFC patients reported increased specific religious
      beliefs after brain injury. CONCLUSIONS: The findings support the False Tagging
      Theory and suggest that the vmPFC is critical for psychological doubt and
      resistance to authoritarian persuasion.

PMID- 22612577
TI  - Deficits in concept formation in amyotrophic lateral sclerosis.
AB  - OBJECTIVE: Amyotrophic Lateral Sclerosis (ALS) is associated with impaired
      executive control. The aim of the current research was to test the hypothesis
      that concept formation deficits associated with an extramotor neurocognitive
      network involving executive and semantic resources can be found in some ALS
      patients. METHOD: Forty-one patients with clinically definite ALS were assessed
      with Delis Kaplan Executive Function System Sorting Test (D-KEFS), a measure of
      concept formation requiring patients to manipulate verbal and visual semantic
      information and neuropsychological tests measuring naming, semantic memory, and
      executive control. Using D-KEFS scale scores, a k-mean cluster analysis
      specifying a 3-group solution was able to classify ALS patients into groups
      presenting with mildly impaired, average, and above average sorting test
      performance. High-resolution T1 structural MRI was used to examine cortical
      thickness in a subset of 16 ALS patients. RESULTS: Stepwise regression analyses
      related free and recognition sorting test performance to measures of action
      naming, single word semantic knowledge, and mental search/working memory. MRI
      studies found widespread cortical thinning involving bilateral frontal, temporal,
      and parietal regions. Regression analyses related recognition sorting performance
      to reduced MRI cortical thickness involving the left prefrontal and left parietal
      cortex. CONCLUSIONS: An extramotor cognitive network is associated with impaired
      concept formation in ALS.

PMID- 22612578
TI  - Revised associative inference paradigm confirms relational memory impairment in
      schizophrenia.
AB  - OBJECTIVE: Patients with schizophrenia have widespread cognitive impairments,
      with selective deficits in relational memory. We previously reported a
      differential relational memory deficit in schizophrenia using the Associative
      Inference Paradigm (AIP), a task suggested by the Cognitive Neuroscience
      Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative to
      examine relational memory. However, the AIP had limited feasibility for testing
      in schizophrenia because of high attrition of schizophrenia patients during
      training. Here we developed and tested a revised version of the AIP to improve
      feasibility. METHOD: 30 healthy control and 37 schizophrenia subjects received 3
      study-test sessions on 3 sets of paired associates: H-F1 (house paired with
      face), H-F2 (same house paired with new face), and F3-F4 (two novel faces). After
      training, subjects were tested on the trained, noninferential Face-Face pairs (F3
      F4) and novel, inferential Face-Face pairs (F1-F2), constructed from the faces of
      the trained House-Face pairs. RESULTS: Schizophrenia patients were significantly
      more impaired on the inferential F1-F2 pairs than the noninferential F3-F4 pairs,
      providing evidence for a differential relational memory deficit. Only 8% of
      schizophrenia patients were excluded from testing because of poor training
      performance. CONCLUSIONS: The revised AIP confirmed the previous finding of a
      relational memory deficit in a larger and more representative sample of
      schizophrenia patients.

PMID- 22612579
TI  - Switching to biphasic insulin aspart 30/50/70 from biphasic human insulin 30/50
      in patients with type 2 diabetes in normal clinical practice: observational study
      results.
AB  - OBJECTIVE: To investigate the safety and efficacy of switching to biphasic
      insulin aspart (BIAsp) 30, 50 or 70 in patients with type 2 diabetes previously
      treated with biphasic human insulin (BHI) 30/50 (with or without oral glucose
      lowering drugs) in routine clinical practice. METHODS: This was a 26-week,
      prospective, observational study conducted in Belgium and Luxembourg. Data were
      collected at baseline before patients switched and at 12 and 26 weeks after
      starting BIAsp 30, 50 or 70. Safety endpoints were incidence and rate of
      hypoglycemia (major, minor, nocturnal), adverse events and body-weight changes.
      Efficacy assessments included HbA(1c) and 7-point self-measured plasma glucose
      (PG) profiles. Changes from baseline were analyzed using paired t-tests. RESULTS:
      Of 592 patients analyzed, 72% switched to twice-daily BIAsp and 20% to three
      times daily BIAsp. Upon switching, 27% of patients received intensified treatment
      (i.e., more daily doses than with their previous BHI). At all three data
      collection points, approximately two-thirds of patients were taking BIAsp 30 and
      approximately one-third were taking BIAsp 50; very few patients took BIAsp 70.
      Mean total daily insulin dose increased significantly from baseline (51.2 U) to
      26 weeks (54.3 U) and mean time of intake before meals changed from 17 minutes
      for BHI to ~3 minutes with BIAsp. Incidence of hypoglycemia did not change during
      the study (baseline: 30.7%, week 26: 29.2%). HbA(1c) improved significantly from
      baseline (7.9 %) to weeks 12 and 26 (7.6% and 7.5%, respectively; p < 0.001).
      Mean PG profiles also showed significant improvements. As this is an
      observational study, some limitations should be considered such as the absence of
      a control group and a possible bias of increased medical attention. CONCLUSIONS:
      Patients with long-standing type 2 diabetes can switch safely from BHI to BIAsp
      therapy, even if they receive intensified treatment, and they have no problems
      changing the timing of their insulin injections.

PMID- 22612580
TI  - A prescription for clinical immunology: the pills are available and ready for
      testing. A review.
AB  - OBJECTIVE: Modern immunology has been extremely successful in elucidating many
      features of the immune system, but not in stemming pandemics of non-infectious,
      immune-related disease associated with industrialized populations. These
      pandemics involve a broad range of allergic, autoimmune, and inflammatory
      diseases, potentially including neuroinflammatory-associated disorders. It is the
      purpose of this review to outline the literature pointing toward the causes and
      potential treatments of these problems. CONCLUSIONS: A wide range of evidence
      from the fields of clinical medicine, biomedical research, evolutionary biology,
      anthropology, epidemiology, immunology, and ecology point to the conclusion that
      pandemics of non-infectious, immune-related conditions arise from consequences of
      industrialization. Primary among these consequences is the loss of helminths from
      the ecosystem of the human body, the 'human biome'. In this view, helminths
      comprise a 'keystone species' of the human biome, and their loss is profoundly
      felt as pandemics of non-infectious, immune-related disease. Fortunately,
      evidence indicates that the consequences of industrialization that cause immune
      disease, such as helminth depletion, can be effectively avoided. Using this
      approach, it is expected that further pandemics of immune disease may be
      prevented, although it remains to be established whether prophylaxis rather than
      treatment of disease is required for some disorders. Thus, it is predicted that
      those who will succeed in curing and preventing immune-related disease will focus
      on addressing 'evolutionary mismatches' rather than simply on the molecular and
      genetic underpinnings of immunological disorders.

PMID- 22612581
TI  - A hybrid approach for continuous detection of sleep-wakefulness fluctuations:
      validation in patients with Cheyne-Stokes respiration.
AB  - Fluctuations in sleep/wake state have been proposed as an important mechanism
      contributing to the development of oscillatory breathing patterns, including
      Cheyne-Stokes respiration in patients with heart failure. In order to properly
      assess the interactions between changes in state and changes in ventilatory
      parameters, a methodology capable of continuously and reliably detecting state
      transitions is needed. Traditional fixed-epoch analysis of polysomnographic
      recordings is not suitable for this purpose. Moreover, visual identification of
      changes in the dominant electroencephalogram activity at the transition from
      wakefulness to sleep and vice versa is often very subjective. We have therefore
      developed a hybrid approach--including both visual scoring and computer-based
      procedures--for continuous analysis of state transitions from polysomnographic
      recordings, specifically tailored for fluctuations between wakefulness and non
      rapid eye movement-1 and -2 sleep. The overall analysis process comprises three
      major phases: (1) manual identification of relevant
      electroencephalogram/electrooculogram features and events, including a sample of
      unequivocal alpha and theta-delta activity; (2) automatic statistical
      discrimination of dominant electroencephalogram activity; and (3) state
      classification (wakefulness, non-rapid eye movement-1 and -2). The latter is
      carried out by merging information from visual scoring with the output of the
      discriminator. Validation has been carried out in 16 patients with heart failure
      during daytime Cheyne-Stokes respiration, using a training and testing set of
      electroencephalogram polysomnograms. The statistical discriminator correctly
      classified 99.1 +/- 1.4% and 99.2 +/- 1.1% of unequivocal alpha and theta-delta
      activity. This approach has therefore the potential to be used to reliably
      measure the incidence and location of sleep-wake transitions during abnormal
      breathing patterns, as well as their temporal relationship with major ventilatory
      events.

PMID- 22612582
TI  - Brain aromatase and circulating corticosterone are rapidly regulated by combined
      acute stress and sexual interaction in a sex-specific manner.
AB  - Neural production of 17beta-oestradiol via aromatisation of testosterone may play
      a critical role in rapid, nongenomic regulation of physiological and behavioural
      processes. In brain nuclei implicated in the control of sexual behaviour, sexual
      or stressfull stimuli induce, respectively, a rapid inhibition or increase in
      preoptic aromatase activity (AA). In the present study, we tested quail that were
      either nonstressed or acutely stressed (15 min of restraint) immediately before
      sexual interaction (5 min) with stressed or nonstressed partners. We measured
      nuclei-specific AA changes, corresponding behavioural output, fertilisation rates
      and corticosterone (CORT) concentrations. In males, sexual interaction rapidly
      reversed stress-induced increases of AA in the medial preoptic nucleus (POM).
      This time scale (< 5 min) highlights the dynamic potential of the aromatase
      system to integrate input from stimuli that drive AA in opposing directions.
      Moreover, acute stress had minimal effects on male behaviour, suggesting that the
      input from the sexual stimuli on POM AA may actively preserve sexual behaviour
      despite stress exposure. We also found distinct sex differences in contextual
      physiological responses: males did not show any effect of partner status, whereas
      females responded to both their stress exposure and the male partner's stress
      exposure at the level of circulating CORT and AA. In addition, fertilisation
      rates and female CORT correlated with the male partner's exhibition of sexually
      aggressive behaviour, suggesting that female perception of the male can affect
      their physiology as much as direct stress. Overall, male reproduction appears
      relatively simple: sexual stimuli, irrespective of stress, drives major neural
      changes including rapid reversal of stress-induced changes of AA. By contrast,
      female reproduction appears more nuanced and context specific, with subjects
      responding physiologically and behaviourally to stress, the male partner's stress
      exposure, and female-directed male behaviour.

PMID- 22612584
TI  - Aggregate transitions in aqueous solutions of sodium dodecylsulfate with a
      "gemini-type" organic salt.
AB  - Effects of a "gemini-type" organic salt 1,2-bis(2-benzylammoniumethoxy) ethane
      dichloride (BEO) on the aggregation behavior of sodium dodecylsulfate (SDS) have
      been investigated by turbidity, surface tension, isothermal titration
      microcalorimetry, dynamic light scattering, cryogenic transmission electron
      microscopy, (1)H NMR spectroscopy, and differential scanning microcalorimetry.
      The aggregation behavior of the SDS/BEO mixed aqueous solution shows strong
      concentration and ratio dependence. For the SDS/BEO solution with a molar ratio
      of 5:1, large loose irregular aggregates, vesicles, and long thread-like micelles
      are formed in succession with the increase of the total SDS and BEO
      concentration. Because BEO has two positive charges, the SDS/BEO solution may
      consist of the (SDS)(2)-BEO gemini-type complex, the SDS-BEO complex and extra
      SDS. The aggregation ability and surface activity of the SDS/BEO mixture exhibit
      the characteristics of gemini-type surfactants. Along with the results of DSC and
      (1)H NMR, the (SDS)(2)-BEO gemini-type structure is confirmed to exist in the
      system. This work provides an approach to construct the surfactant systems with
      the characteristics of gemini surfactants through intermolecular interaction
      between a two-charged organic salt and oppositely charged single-chain
      surfactants.

PMID- 22612585
TI  - gamma-Aminobutyric acid production by culturable bacteria from the human
      intestine.
AB  - AIMS: To assess the ability of human intestinally derived strains of
      Lactobacillus and Bifidobacterium to produce gamma-aminobutyric acid (GABA).
      METHODS AND RESULTS: Strains of Lactobacillus and Bifidobacterium were grown in
      medium containing monosodium glutamate (MSG). Growth of the bacteria and
      conversion of MSG to GABA were measured. Of 91 intestinally derived bacteria
      assessed, one Lactobacillus strain and four strains of Bifidobacterium produced
      GABA. Lactobacillus brevis DPC6108 was the most efficient of the strains tested,
      converting up to 90% [corrected] of MSG to GABA. The ability of the cultured
      intestinal strains to produce GABA was investigated using a simple pH-controlled
      anaerobic faeces-based fermentation, supplemented with 30 mg ml-1 MSG. The
      addition of Lact. brevis DPC6108 to a faeces-based fermentation significantly
      increased the GABA concentration (P < 0.001), supporting the notion that this
      biosynthesis could occur in vivo. CONCLUSIONS: The production of GABA by
      bifidobacteria exhibited considerable interspecies variation. Lactobacillus
      brevis and Bifidobacterium dentium were the most efficient GABA producers among
      the range of strains tested. The addition of Lact. brevis DPC6108 to the
      culturable gut microbiota increased the GABA concentration in fermented faecal
      slurry at physiological pH. SIGNIFICANCE AND IMPACT OF THE STUDY: Identification
      of optimal MSG conversion to GABA by particular cultured elements of the
      commensal intestinal microbiota and the demonstration that this can occur under
      simulated in vivo conditions offer new prospects for microbiota modulation to
      promote health.

PMID- 22612586
TI  - Cine substitution of arenes using the aryl carbamate as a removable directing
      group.
AB  - An efficient and controlled means to achieve a rare cine substitution of arenes
      is reported. The methodology relies on the strategic use of aryl O-carbamates as
      readily removable directing groups for arene functionalization. The removal of
      aryl carbamates is achieved by employing an air-stable Ni(II) precatalyst, along
      with an inexpensive reducing agent, to give synthetically useful yields across a
      range of substrates. The net cine substitution process offers a new strategy for
      analogue synthesis, which complements the well-established logic for achieving
      arene functionalization by ipso substitution.

PMID- 22612587
TI  - Dechlorinating microorganisms in a sedimentary rock matrix contaminated with a
      mixture of VOCs.
AB  - Microbiological characterizations of contaminant biodegradation in fractured
      sedimentary rock have primarily focused on the biomass suspended in groundwater
      samples and disregarded the biomass attached to fractures and in matrix pores. In
      fractured sedimentary rock, diffusion causes nearly all contaminant mass to
      reside in porous, low-permeability matrix. Microorganisms capable of contaminant
      degradation can grow in the matrix pores if the pores and pore throats are
      sufficiently large. In this study, the presence of dechlorinating microorganisms
      in rock matrices was investigated at a site where a fractured, flat-lying,
      sandstone-dolostone sequence has been contaminated with a mixture of chlorinated
      and aromatic hydrocarbons for over 40 years. The profile of organic contaminants
      as well as the distribution and characterization of the microbial community
      spatial variability was obtained through depth-discrete, high-frequency sampling
      along a 98-m continuous rock core. Dechlorinating microorganisms, such as
      Dehalococcoides and Dehalobacter, were detected in the rock matrices away from
      fracture surfaces, indicating that biodegradation within the rock matrix blocks
      should be considered as an important component of the system when evaluating the
      potential for natural attenuation or remediation at similar sedimentary rock
      sites.

PMID- 22612588
TI  - Scalp and chest cutaneous metastases of cholangiocarcinoma.

PMID- 22612589
TI  - Mental health problems and post-migration stress among multi-traumatized refugees
      attending outpatient clinics upon resettlement to Norway.
AB  - Refugees have often been exposed to multiple traumas making them prone to mental
      health problems later. The aim of this study is to describe the prevalence and
      symptom load of psychiatric disorders in refugees admitted to psychiatric
      outpatient clinics and to investigate the relationship between multiple exposure
      to traumatic events, the severity of traumatic symptoms and post-migration
      stressors. A clinical sample of 61 refugee outpatients from psychiatric clinics
      in Southern Norway was cross-sectionally examined using three structured clinical
      interviews (SCID-PTSD, SIDES and MINI) and self-report psychometric instruments
      (HSCL-25, IES-R). Post-traumatic Stress Disorder (PTSD) was diagnosed in 82% of
      the patients, while Disorders of Extreme Stress Not Otherwise Specified (DESNOS)
      was present in 16% of them. Comorbidity was considerable; 64% of the patients had
      both PTSD and major depression disorder (MDD) and 80% of those who had PTSD had
      three or more additional diagnoses. Multi-traumatized refugees in outpatient
      clinics have high prevalence of PTSD, DESNOS, comorbid depression and anxiety
      disorders. A more severe symptomatology was found in patients diagnosed with both
      PTSD and DESNOS, than in those diagnosed with only PTSD. Higher rates of
      unemployment, weak social network and weak social integration were also prevalent
      in these outpatients, and related to increased psychiatric comorbidity and
      severity of symptoms. Further research may clarify the existence of a cumulative
      relationship between pre-resettlement traumas and post-resettlement stressors in
      the mental health of refugees, which in turn may help to improve therapeutic
      interventions.

PMID- 22612590
TI  - Management of a Klippel-Trenaunay syndrome in pregnant women with mega-cisterna
      magna and splenic and vulvar varices at birth: a case report.
AB  - Klippel-Trenaunay syndrome (KTS) is a rare, sporadic and complex malformation
      characterized by the clinical triad of: (i) capillary malformation (port-wine
      stain); (ii) soft tissue and bone hypertrophy or occasionally, hypertrophy of one
      lower limb; and (iii) atypical lateral varicosity. The maternal and fetal risks
      associated with pregnancy in women with KTS are proportional to disease severity,
      which can be exacerbated by pregnancy. Complications include bleeding,
      disseminated intravascular coagulation, thromboembolic events and pain. Here, we
      report the case of a pregnant woman with KTS who had an uneventful pregnancy,
      labor and postpartum course, but had splenic and large vulvar vein varices. The
      obstetrical course of women with KTS varies. Management is largely conservative
      and multidisciplinary approaches form the mainstay for managing these patients
      based on their symptoms.

PMID- 22612591
TI  - Characterization of yatakemycin gene cluster revealing a radical S
      adenosylmethionine dependent methyltransferase and highlighting spirocyclopropane
      biosynthesis.
AB  - Yatakemycin (YTM), an antitumor natural product, represents the most potent
      member of a class of potent anticancer natural products including CC-1065 and
      duocarmycins. Herein we describe the biosynthetic gene cluster of YTM, which was
      identified by genome scanning of Streptomyces sp. TP-A0356. This cluster consists
      of 31 open reading frames (ORFs) and was localized to a 36 kb DNA segment.
      Moreover, its involvement in YTM biosynthesis was confirmed by cluster deletion,
      gene replacement, and complementation. Inactivation of ytkT, which encodes a
      radical S-adenosylmethionine (SAM) protein, created a mutant strain that failed
      to produce YTM but accumulated a new metabolite, which was structurally
      elucidated as a precursor that was related to the formation of the cyclopropane
      ring. More importantly, biochemical characterization of the radical SAM-dependent
      enzyme YtkT revealed that it is a novel C-methyltransferase and contributes to an
      advanced intermediate during formation of the cyclopropane ring through a radical
      mechanism in the YTM biosynthetic pathway. On the basis of in silico analysis,
      genetic experiments, structure elucidation of the novel intermediate, and
      biochemical characterization, a biosynthetic pathway for yatakemycin was
      proposed, which sets the stage to further investigate the novel enzymatic
      mechanisms and engineer the biosynthetic machinery for the production of novel
      analogues.

PMID- 22612592
TI  - Nickel-catalyzed carboxylation of aryl and vinyl chlorides employing carbon
      dioxide.
AB  - Nickel-catalyzed carboxylation of aryl and vinyl chlorides employing carbon
      dioxide has been developed. The reactions proceeded under a CO(2) pressure of 1
      atm at room temperature in the presence of nickel catalysts and Mn powder as a
      reducing agent. Various aryl chlorides could be converted to the corresponding
      carboxylic acid in good to high yields. Furthermore, vinyl chlorides were
      successfully carboxylated with CO(2). Mechanistic study suggests that Ni(I)
      species is involved in the catalytic cycle.

PMID- 22612593
TI  - A Bayesian approach to in silico blood-brain barrier penetration modeling.
AB  - The human blood-brain barrier (BBB) is a membrane that protects the central
      nervous system (CNS) by restricting the passage of solutes. The development of
      any new drug must take into account its existence whether for designing new
      molecules that target components of the CNS or, on the other hand, to find new
      substances that should not penetrate the barrier. Several studies in the
      literature have attempted to predict BBB penetration, so far with limited success
      and few, if any, application to real world drug discovery and development
      programs. Part of the reason is due to the fact that only about 2% of small
      molecules can cross the BBB, and the available data sets are not representative
      of that reality, being generally biased with an over-representation of molecules
      that show an ability to permeate the BBB (BBB positives). To circumvent this
      limitation, the current study aims to devise and use a new approach based on
      Bayesian statistics, coupled with state-of-the-art machine learning methods to
      produce a robust model capable of being applied in real-world drug research
      scenarios. The data set used, gathered from the literature, totals 1970 curated
      molecules, one of the largest for similar studies. Random Forests and Support
      Vector Machines were tested in various configurations against several chemical
      descriptor set combinations. Models were tested in a 5-fold cross-validation
      process, and the best one tested over an independent validation set. The best
      fitted model produced an overall accuracy of 95%, with a mean square contingency
      coefficient (phi) of 0.74, and showing an overall capacity for predicting BBB
      positives of 83% and 96% for determining BBB negatives. This model was adapted
      into a Web based tool made available for the whole community at
      http://b3pp.lasige.di.fc.ul.pt.

PMID- 22612594
TI  - The number of p16INK4a positive cells in human skin reflects biological age.
AB  - Cellular senescence is a defense mechanism in response to molecular damage which
      accumulates with aging. Correspondingly, the number of senescent cells has been
      reported to be greater in older than in younger subjects and furthermore
      associates with age-related pathologies. Inter-individual differences exist in
      the rate at which a person ages (biological age). Here, we studied whether
      younger biological age is related to fewer senescent cells in middle-aged
      individuals with the propensity for longevity, using p16INK4a as a marker for
      cellular senescence. We observed that a younger biological age associates with
      lower levels of p16INK4a positive cells in human skin.

PMID- 22612595
TI  - Psoriasiform eruption and oral ulcerations as adverse effects of topical 5%
      imiquimod treatment in children: a report of four cases.
AB  - Imiquimod 5% cream is a topical immune-response modifier indicated in the
      treatment of multiple cutaneous conditions including actinic keratoses,
      superficial basal cell carcinoma, and condylomata acuminata. In children, it has
      been approved only for ages 12 and older in the treatment of external genital and
      perianal warts. It has also been used off label for a variety of pediatric skin
      disorders, including molluscum contagiosum (MC), trichoepitheliomas, verrucae
      plana, and verrucae vulgaris. Local and systemic adverse reactions have been
      reported, with the most frequently reported events being application site
      reactions including itching, burning, erythema, and erosion. Although these local
      reactions are well known, other rare local and systemic reactions can occur.
      There have been multiple case reports in adults of rare adverse cutaneous
      reactions occurring with imiquimod, but few have been reported in children. We
      present four cases of rare adverse cutaneous reactions. In all cases, the
      children were being treated with imiquimod 5% cream for verrucae or MC. Two of
      these patients developed a localized psoriasiform eruption, and two developed
      mucosal ulcerations. 

PMID- 22612597
TI  - Why you should care about screening flexible sigmoidoscopy.

PMID- 22612598
TI  - Isotope-labeling of the fibril binding compound FSB via a Pd-catalyzed double
      alkoxycarbonylation.
AB  - We have synthesized two isotopically labeled variants of the beta-amyloid binding
      compound FSB possessing (13)C-labels on the two terminal aryl carboxylic acid
      moieties. One of these was also fully deuterated on the olefinic spacers. The
      (13)C-isotope labeling was achieved applying a Pd-catalyzed methoxycarbonylation
      of the corresponding aryl chlorides with externally (ex situ) generated (13)C
      labeled CO. Application of the Shirakawa-Hayashi protocol for the Pd-catalyzed
      reduction of a dialkyne intermediate using D(2)O allowed for the selective
      deuterium labeling of the two trans-C,C double bonds of FSB.

PMID- 22612599
TI  - Inhibitors of the anaplastic lymphoma kinase.
AB  - INTRODUCTION: Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase
      normally expressed in the developing nervous tissue. Genetic alterations of ALK
      are associated with a number of cancers, including anaplastic large cell lymphoma
      (ALCL) and a subset of non-small cell lung cancer (NSCLC). Standard therapies for
      these diseases include surgery plus unspecific cytotoxic agents, with a low
      therapeutic window and significant treatment-associated systemic toxicity. A few
      small-molecule inhibitors of ALK kinase activity have been described in the
      recent years, some of which are currently undergoing clinical evaluation. AREAS
      COVERED: Literature was searched for all ALK inhibitors that have entered
      clinical investigation, including published research articles and meeting
      abstracts. Data on pharmacokinetics, safety and efficacy of crizotinib, as well
      as preliminary clinical data for second-generation compounds, are reviewed. The
      issue of drug resistance is discussed. EXPERT OPINION: Understanding the specific
      genetic aberration that causes cancer development and progression allows major
      advances in cancer therapy. Along the same way shown by imatinib in chronic
      myeloid leukemia, compounds that selectively target ALK are bringing a revolution
      in the treatment of ALK-positive tumors. Crizotinib has just been approved, and
      new more potent ALK inhibitors will shortly follow. These molecules represent
      another excellent proof-of-principle for targeted therapy.

PMID- 22612600
TI  - Pervasive developmental disorders in children of hyperandrogenic women with
      polycystic ovary syndrome: a longitudinal case-control study.
AB  - OBJECTIVE: Foetal exposure to high testosterone concentrations seems to be
      involved in the development of mammalian brain and related to pervasive
      developmental disorders (PDDs). The aim of the current study was to test the
      hypothesis that children born from hyperandrogenic women with polycystic ovary
      syndrome (PCOS) are at higher risk of PDDs. DESIGN: Longitudinal case-control
      study. PATIENTS: Thirty pregnant PCOS patients with hyperandrogenaemia and other
      45 pregnant healthy women were followed during pregnancy. All women had a healthy
      baby. MEASUREMENTS: Clinical evaluations and biochemical assays of the mothers
      during pregnancy and after delivery were performed. The children's versions of
      the Autism-Spectrum Quotient (AQ-C), the Empathy Quotient (EQ-C) and Systemizing
      Quotient (SQ-C) tests were administered. RESULTS: Total AQ-C and communication
      scores were significantly higher for children of PCOS patients. Stratifying our
      population according to sex, total AQ-C, communication and attention switching
      subscores were significantly higher only for daughters of PCOS patients. EQ-C and
      SQ-C scores resulted in significantly lower and higher scores, respectively, only
      in daughters of PCOS patients in comparison with those of healthy non-PCOS
      controls. AQ-C, EQ-C and SQ-C scores, irrespective of the studied group and/or
      subclassification by gender, were significantly influenced by amniotic
      testosterone levels. CONCLUSIONS: Daughters of mothers affected by
      hyperandrogenic PCOS seem to have a higher risk for PDDs probably due to an
      unbalanced prenatal exposure to high levels of testosterone.

PMID- 22612601
TI  - Efficacy of several candidate protein biomarkers in the differentiation of
      vaginal from buccal epithelial cells.
AB  - Currently, there is no accurate method to differentiate vaginal epithelial cells
      from buccal epithelial cells in biological samples typically encountered in
      forensic casework. This study tested the expression of a selection of candidate
      proteins in buccal and vaginal epithelial cells. We investigated six candidate
      biomarkers, such as loricrin, vimentin, stratifin, cytokeratin 4, cytokeratin 13,
      small proline-rich protein 2, and involucrin, using Western blot analysis on
      whole protein extracts and immunohistochemistry (IHC) on intact cells in an
      attempt to identify cell-specific markers that would differentiate these cells by
      microscopy. Involucrin, loricrin, and stratifin showed differential expression
      during Western blot analysis and were carried through to IHC. Although proteins
      unique to vaginal epithelial cells and buccal epithelial cells were not
      identified from among the proteins tested, the increased expression levels of two
      proteins, loricrin and stratifin in vaginal cells, when compared to buccal cells,
      do provide encouraging results in the search for epithelial cell-specific
      markers.

PMID- 22612602
TI  - The influence of semantic relationships on older adult map memory.
AB  - Research has shown that nonspatial features, including semantic categories, can
      bias younger adults' spatial location memory. For example, semantically related
      information is remembered as being closer in space than semantically unrelated
      information (Hirtle & Mascolo, 1986). These findings suggest that verbal
      information is concurrently encoded with spatial information and influences
      younger adults' spatial information retrieval. The present study explored whether
      older adults have a similar dependency between verbal and spatial information. In
      Experiment 1, older and younger adults learned maps depicting semantically
      categorizable landmarks. After learning, participants completed landmark free
      recall and distance estimation tasks. Younger adults recalled more landmarks from
      semantically organized maps compared with older adults. In addition, younger
      adults were more likely to underestimate the distance between semantically
      related landmarks than were older adults. Experiment 2 examined whether
      supportive instructions would influence older adults' use of verbal information
      when learning maps. When given instructions that encouraged semantic feature use,
      older adults remembered more landmarks, were more likely to cluster landmarks
      semantically, and demonstrated biases in distance estimation based on semantic
      relationships. These findings suggest that verbal influences on spatial/map
      learning in older adults depends on explicit instructions or environmental
      support at encoding.

PMID- 22612604
TI  - The Women's Health Initiative - a decade of progress.

PMID- 22612603
TI  - Terminal decline in motor function.
AB  - The study aim was to test the hypothesis that motor function undergoes
      accelerated decline proximate to death. As part of a longitudinal clinical
      pathologic study, 124 older Roman Catholic nuns, priests, and monks completed at
      least 7 annual clinical evaluations, died, and underwent brain autopsy and
      uniform neuropathologic examination. Each evaluation included administration of
      11 motor tests and 19 cognitive tests from which global measures of motor and
      cognitive function were derived. The global motor measure (baseline M = 0.82, SD
      = 0.21) declined a mean 0.024 unit per year (95% confidence interval [CI]: 
      0.032, -0.016) until a mean of 2.46 years (95% CI: -2.870, -2.108) before death
      when rate of decline increased nearly fivefold to -0.117 unit per year (95% CI: 
      0.140, -0.097). The global cognitive measure (baseline M = 0.07, SD = 0.45)
      declined a mean of 0.027-unit per year (95% CI: -0.041, -0.014) until a mean of
      2.76 years (95% CI: -3.157, -2.372) before death when rate of decline increased
      more than 13-fold to -0.371 unit per year (95% CI: -0.443, -0.306). Onset of
      terminal motor decline was highly correlated with onset of terminal cognitive
      decline (r = .94, 95% CI: 0.81, 0.99), but rates of motor and cognitive change
      were not strongly correlated (preterminal r = .20, 95% CI: -0.05, 0.38; terminal
      r = .34, 95% CI: 0.03, 0.62). Higher level of plaques and tangles was associated
      with earlier onset of terminal decline in motor function, but no pathologic
      measures were associated with rate of preterminal or terminal motor decline. The
      results demonstrate that motor and cognitive functions both undergo a period of
      accelerated decline in the last few years of life.

PMID- 22612605
TI  - Have we come full circle - or moved forward? The Women's Health Initiative 10
      years on.
AB  - In mid-summer 2002, the announcement that the Women's Health Initiative (WHI)
      trial of combination hormone therapy (HRT) had stopped jolted the field of
      women's health. It set off a cascade that first stunned, then meaningfully
      changed the future for millions of women, their partners, and tens of thousands
      of clinicians and scientists. With 10 years' hindsight, we can begin to put the
      lessons learned from the WHI HRT trials into perspective. These trials were
      primarily designed to test whether women considerably past menopause, and mostly
      asymptomatic, experienced treatment benefits from HRT expected from studies of
      generally symptomatic women who started near menopause. The definitive answer was
      'no'. Unfortunately, the findings were generalized to all postmenopausal women
      regardless of age. Data accumulated from the WHI and other studies over the past
      decade have shown that, in women with symptoms or other indications, initiating
      HRT near menopause - the classic pattern of use - will probably provide a
      favorable benefit : risk ratio. Spurred by the WHI, many hypotheses and some
      insights about potential mechanisms for HRT effects on diverse organ systems have
      emerged, along with new perspectives on regimens, compounds, and routes of
      administration. This overview provides an historical perspective on the WHI
      design and the evolution of its message; summarizes current perspectives and
      insights contributed by eminent colleagues; reviews the state of the art; and
      looks to the future. We have come full circle in some ways, with mounting
      evidence supporting benefit for HRT started near menopause and with hard lessons
      learned about pathophysiology, publicity and interpreting data. Now we move on.

PMID- 22612606
TI  - Quality of life and the role of menopausal hormone therapy.
AB  - The quality of life of countless menopausal women world-wide has been
      significantly diminished following the sensationalist reporting of the Women's
      Health Initiative (WHI) and the resulting 50% or more decline in the use of
      hormone replacement therapy (HRT) over the subsequent 10 years. Quality of life
      is difficult to measure as there are so many contributing factors and a large
      number of different instruments, some of which assess general health and only a
      few which specifically include symptoms related to menopause. HRT improves
      quality of life of symptomatic menopausal women and some studies of the effects
      of HRT provide reliable evidence on quality of life other than reduction in
      vasomotor symptoms. Until there is a better understanding of the minimal risks of
      HRT for the majority of women, too many will continue to suffer a reduced quality
      of life unnecessarily.

PMID- 22612607
TI  - The timing hypothesis for coronary heart disease prevention with hormone therapy:
      past, present and future in perspective.
AB  - Over the past decade, two informative events in primary prevention of coronary
      heart disease (CHD) have occurred for women's health. The first concerns hormone
      replacement therapy (HRT) where data have come full circle from presumed harm to
      consistency with observational data that HRT initiation in close proximity to
      menopause significantly reduces CHD and overall mortality. The other concerns sex
      specific efficacy of CHD primary prevention therapies where lipid-lowering and
      aspirin therapy have not been conclusively shown to significantly reduce CHD and,
      more importantly, where there is lack of evidence that either therapy reduces
      overall mortality in women. Cumulated data support a 'window-of-opportunity' for
      maximal reduction of CHD and overall mortality and minimization of risks with HRT
      initiation before 60 years of age and/or within 10 years of menopause and
      continued for 6 years or more. There is a substantial increase in quality
      adjusted life-years over a 5-30-year period in women who initiate HRT in close
      proximity to menopause, supporting HRT as a highly cost-effective strategy for
      improving quality-adjusted life. Although primary prevention therapies and HRT
      contrast in their efficacy to significantly reduce CHD and especially overall
      mortality in postmenopausal women, the magnitude and types of risks associated
      with HRT are similar to those associated with other medications commonly used in
      women's health. The cumulated data highlight the importance of studying the HRT
      cardioprotective hypothesis in women representative of those from whom the
      hypothesis was generated.

PMID- 22612609
TI  - Estrogen and progestogen effect on venous thromboembolism in menopausal women.
AB  - Prior to 1996, the use of postmenopausal estrogen was not believed to increase
      the risk of venous thrombosis. Subsequent studies, particularly the prospective,
      randomized, double-blind, clinical trial of the Women's Health Initiative, have
      clearly shown an increase in the incidence and risk of venous thrombosis in
      postmenopausal women using conjugated equine estrogens with or without
      medroxyprogesterone acetate. The risk of venous thrombosis in postmenopausal
      women is also increased by obesity and age. Oral hormone therapy has been used
      principally for management of menopausal symptoms. Transdermal estrogens have not
      been used as extensively in the United States but have a significant use in
      Europe. Recent observational studies have indicated no increased risk of venous
      thrombosis with use of transdermal estrogens. Norpregnane derivatives have been
      associated with an increased risk of venous thrombosis, suggesting that
      progestins may contribute to the increased risk in postmenopausal women using
      estrogen plus progestin therapy.

PMID- 22612608
TI  - Hormone therapy and the risk of stroke: perspectives 10 years after the Women's
      Health Initiative trials.
AB  - Principal findings on stroke from the Women's Health Initiative (WHI) clinical
      trials of hormone therapy indicate that estrogen, alone or with a progestogen,
      increases a woman's risk of stroke. These results were not unexpected, and
      research during the past decade has tended to support these findings. Consistent
      evidence from clinical trials and observational research indicates that standard
      dose hormone therapy increases stroke risk for postmenopausal women by about one
      third; increased risk may be limited to ischemic stroke. Risk is not modified by
      age of hormone initiation or use, or by temporal proximity to menopause, and risk
      is similar for estrogen plus progestogen and for unopposed estrogen. Limited
      evidence implies that lower doses of transdermal estradiol (<=50 MUg/day) may not
      alter stroke risk. For women less than 60 years of age, the absolute risk of
      stroke from standard-dose hormone therapy is rare, about two additional strokes
      per 10 000 person-years of use; the absolute risk is considerably greater for
      older women. Other hormonally active compounds - including raloxifene, tamoxifen,
      and tibolone - can also affect stroke risk.

PMID- 22612610
TI  - Hormone therapy and breast cancer risk 10 years after the WHI.
AB  - Ten years after the publication of the first Women's Health Initiative (WHI)
      report, a substantial decrease in hormone replacement therapy (HRT) has been
      observed world-wide. Fear of developing breast cancer represents one of the
      reasons for an important shift toward alternatives for treatment of menopause
      symptoms or abstention from therapy altogether. Many publications in the
      scientific and lay press have emphasized the magnitude of the relative risk of
      breast cancer but have not focused on excess or attributable risk. Since the
      original report of the WHI study, new information has been published on risk
      factors for breast cancer related to hormone therapy use. Accordingly, we believe
      it important to review current data and examine excess rather than relative or
      absolute risk. A balanced perspective on excess risk determined from existing
      data suggests that the benefits of HRT for quality of life can outweigh the risks
      in management of a large number of postmenopausal women. In addition, alternative
      strategies for relief of menopausal symptoms are not as effective as HRT in
      treating the climacteric symptoms.

PMID- 22612611
TI  - Colorectal cancer in women: hormone replacement therapy and chemoprevention.
AB  - Colorectal cancer (CRC) accounts for 9.4% of new cancer diagnoses among women
      world-wide. CRC is the third leading cause of incident cancer among women in the
      United States and has immense impact on morbidity and mortality. We summarize
      data on CRC pathogenesis and risk in women. We also review the findings from the
      Women's Health Initiative (WHI) on CRC risk reduction associated with hormone
      replacement therapy (HRT) use. We then review observational studies since the WHI
      which evaluated HRT as a chemopreventive agent for CRC among women. The potential
      mechanisms behind the association between HRT use and CRC are also reviewed. We
      then discuss the requirements for implementation of chemopreventive agents, and
      why HRT should not be used for this indication given current knowledge. Further
      data on the risk-benefit profile of short-term HRT use are needed and will
      determine whether there is any future role for HRT use in the chemoprevention of
      CRC.

PMID- 22612613
TI  - The WHI: the effect of hormone replacement therapy on fracture prevention.
AB  - The Women's Health Initiative (WHI) randomized, controlled trial was the first
      study to prove that hormone replacement therapy (HRT) reduces the incidence of
      all osteoporosis-related fractures in postmenopausal women, even those at low
      risk of fracture. The study authors concluded that the bone-friendly aspect of
      HRT was limited in clinical practice as possible adverse effects outweighed
      possible benefit. On the strength of these publications, regulatory authorities
      downgraded the use of HRT for the prevention of fracture to second-line therapy.
      This article examines the original and subsequent evidence presented by the WHI
      study and concludes that the restrictions placed on HRT as a bone-specific drug
      by regulatory bodies have not withstood the test of time and are not supported by
      the data of the WHI.

PMID- 22612614
TI  - The use of hormone therapy for the maintenance of urogynecological and sexual
      health post WHI.
AB  - BACKGROUND: The loss of estrogen at menopause and the gradual decline in
      testosterone with age are associated with urogenital atrophy and, as a result,
      urogenital tract symptoms, including lower urinary tract symptoms and
      dyspareunia. These symptoms will persist unless treated. OBJECTIVE: To review the
      prevalence of urogenital tract symptoms and sexual health problems associated
      with menopause and the role in the use of hormone therapy for the treatment of
      symptomatic women, with a specific focus on what has been learned since the first
      publication of the Women's Health Initiative (WHI) estrogen and estrogen +
      progestin studies. CONCLUSION: Studies support the use of local estrogen therapy,
      but not systemic estrogen therapy, for the treatment of urge urinary
      incontinence, overactive bladder and to reduce the number of urinary tract
      infections. The current evidence does not favor a beneficial effect on stress
      urinary incontinence. Local estrogen therapy is effective for the treatment of
      dyspareunia caused by vulvovaginal atrophy. Preliminary studies suggest a
      potential role for both intravaginal dehydroepiandrosterone and testosterone in
      the treatment of dyspareunia secondary to vulvovaginal atrophy, however,
      confirmatory studies are required before either therapy can be recommended. Post
      WHI, there is a need for medical practitioners to proactively raise the topic of
      urogynecological and sexual health in order to discuss the most suitable
      treatment option.

PMID- 22612612
TI  - Hormone therapy, dementia, and cognition: the Women's Health Initiative 10 years
      on.
AB  - Principal findings on dementia from the Women's Health Initiative Memory Study
      (WHIMS) showed that conjugated equine estrogens plus medroxyprogesterone acetate
      (CEE/MPA) increase dementia risk in women aged 65 years and above, but not risk
      of mild cognitive impairment. The dementia finding was unexpected, given
      consistent observational evidence that associates use of estrogen-containing
      hormone therapy with reduced risk of Alzheimer's disease. It remains
      controversial whether hormone use by younger postmenopausal women near the time
      of menopause reduces dementia risk or whether WHIMS findings should be
      generalized to younger women. Given the challenges of conducting a primary
      prevention trial to address that question, it is helpful to consider the impact
      of hormone therapy on cognitive test performance, particularly verbal memory, for
      its own sake and as a proxy for dementia risk. The WHI Study of Cognitive Aging
      (WHISCA) showed that CEE/MPA worsened verbal memory, whereas CEE alone had no
      influence on cognition. These findings have been replicated in several
      randomized, clinical trials. The apparent negative effect of CEE/MPA on verbal
      memory does not appear to be age-dependent. Additional investigations are needed
      to understand the impact of other hormonally active compounds on dementia and
      cognitive outcomes.

PMID- 22612615
TI  - Shock, terror and controversy: how the media reacted to the Women's Health
      Initiative.
AB  - Results from the first publication of the Women's Health Initiative trial were
      announced by press release and press conference in July 2002. The announcement
      explained that the combined hormone trial had been terminated early because of
      'increased breast cancer risk'. The dramatic nature of the announcement set the
      tone for the early news reporting from the study and introduced a note of
      confusion into the media's perception of hormone replacement therapy (HRT). Such
      a tone persisted until July 2007, when the trial revised its findings on
      cardiovascular risk. Despite investigators' protests to the contrary, the results
      were perceived by the press as a U-turn, and reinforced the media's confused
      interpretation of the safety and benefits of HRT. We argue that the WHI's
      melodramatic presentation of its results explains the media response.

PMID- 22612616
TI  - Evidence-based assessment of the impact of the WHI on women's health.
AB  - Following the announcement of the first results of the Women's Health Initiative
      (WHI) to the media in 2002, prior to their scientific publication, the resulting
      panic headlines had an immediate and lasting negative effect on use of menopausal
      hormone replacement therapy (HRT) around the world. Rates of use dropped by 40
      80%. Symptomatic women then sought multiple alternative therapies but the
      majority of these have no greater effect than the effect seen from placebo in
      well-conducted trials of HRT. Some of these therapies have risks. Although
      anecdotally most menopause practitioners after 2002 can attest to having to
      counsel large numbers of women with debilitating menopausal symptoms who were too
      frightened to consider HRT, it is difficult to document loss of health-related
      quality of life in large population studies as they were not conducted.
      Similarly, the positive or negative effects of the marked decline in HRT on long
      term morbidities and mortality have yet to be fully assessed. Recent studies have
      shown an increase in postmenopausal fractures and in some, but not all,
      populations a small temporary decline in breast cancer. Cardiovascular outcomes
      may not be apparent for another decade. Short-term, randomized, placebo
      controlled trials confirm that HRT is the only therapy that effectively improves
      health-related quality of life in symptomatic women through a reduction in
      vasomotor and urogenital symptoms, joint pains and insomnia, while improving
      sexuality. The results of the re-analyses of the WHI data and new data from other
      studies do not justify the continuing negative attitude to HRT in symptomatic
      women who start HRT near menopause.

PMID- 22612596
TI  - Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy.
AB  - BACKGROUND: The benefits of endoscopic testing for colorectal-cancer screening
      are uncertain. We evaluated the effect of screening with flexible sigmoidoscopy
      on colorectal-cancer incidence and mortality. METHODS: From 1993 through 2001, we
      randomly assigned 154,900 men and women 55 to 74 years of age either to screening
      with flexible sigmoidoscopy, with a repeat screening at 3 or 5 years, or to usual
      care. Cases of colorectal cancer and deaths from the disease were ascertained.
      RESULTS: Of the 77,445 participants randomly assigned to screening (intervention
      group), 83.5% underwent baseline flexible sigmoidoscopy and 54.0% were screened
      at 3 or 5 years. The incidence of colorectal cancer after a median follow-up of
      11.9 years was 11.9 cases per 10,000 person-years in the intervention group (1012
      cases), as compared with 15.2 cases per 10,000 person-years in the usual-care
      group (1287 cases), which represents a 21% reduction (relative risk, 0.79; 95%
      confidence interval [CI], 0.72 to 0.85; P<0.001). Significant reductions were
      observed in the incidence of both distal colorectal cancer (479 cases in the
      intervention group vs. 669 cases in the usual-care group; relative risk, 0.71;
      95% CI, 0.64 to 0.80; P<0.001) and proximal colorectal cancer (512 cases vs. 595
      cases; relative risk, 0.86; 95% CI, 0.76 to 0.97; P=0.01). There were 2.9 deaths
      from colorectal cancer per 10,000 person-years in the intervention group (252
      deaths), as compared with 3.9 per 10,000 person-years in the usual-care group
      (341 deaths), which represents a 26% reduction (relative risk, 0.74; 95% CI, 0.63
      to 0.87; P<0.001). Mortality from distal colorectal cancer was reduced by 50% (87
      deaths in the intervention group vs. 175 in the usual-care group; relative risk,
      0.50; 95% CI, 0.38 to 0.64; P<0.001); mortality from proximal colorectal cancer
      was unaffected (143 and 147 deaths, respectively; relative risk, 0.97; 95% CI,
      0.77 to 1.22; P=0.81). CONCLUSIONS: Screening with flexible sigmoidoscopy was
      associated with a significant decrease in colorectal-cancer incidence (in both
      the distal and proximal colon) and mortality (distal colon only). (Funded by the
      National Cancer Institute; PLCO ClinicalTrials.gov number, NCT00002540.).

PMID- 22612617
TI  - Future long-term trials of postmenopausal hormone replacement therapy - what is
      possible and what is the optimal protocol and regimen?
AB  - The ideal long-term, randomized, placebo-controlled trial of hormone replacement
      therapy (HRT) from near menopause for up to 30 years to assess major morbidity
      and mortality is impractical because of high cost, participant retention, therapy
      compliance, and continuity of research staff and funding. Also the trial regimen
      may become outdated. It is nihilistic to demand such a long-term trial before
      endorsing HRT. However, medium-term trials using surrogate measures for long-term
      morbidity and mortality are possible and two are near completion. If these
      studies have been able to maintain reasonable participant retention, therapy
      compliance and minimal breach of protocol, they will set standards for trials of
      new HRT regimens. This paper discusses lessons learnt from past attempts at long
      term trials and suggests the currently optimal protocol and cost of assessing new
      HRT regimens to optimize potential benefits and minimize adverse effects. A 5-7
      year randomized, placebo-controlled trial of a flexible transdermal estrogen
      regimen +/- either a selective estrogen receptor modulator, e.g. bazedoxifene, or
      micronized progesterone is discussed. Mild to moderately symptomatic women, 1-4
      years post menopause, can be recruited via general practice and group meetings.
      Future trials should be funded by independent agencies and are high priority in
      women's health.

PMID- 22612618
TI  - Usefulness of a global clinical ichthyosis vulgaris scoring system for predicting
      common FLG null mutations in an adult caucasian population.
AB  - BACKGROUND: Loss of function FLG alleles were first identified as causative of
      ichthyosis vulgaris (IV) and were subsequently found to be major predisposing
      factors for atopic dermatitis (AD) and atopic disorders. OBJECTIVES: To identify
      independent factors associated with the clinical IV phenotype in adult caucasian
      patients with AD and to assess the performance of a global clinical severity
      score of IV in predicting common FLG null mutations. PATIENTS AND METHODS: This
      was a prospective study conducted from January 2007 to June 2008. Adult patients
      attending the department of dermatology with a diagnosis of AD with or without IV
      were eligible to participate. For each patient, five clinical signs of IV were
      scored from 0 to 3 - diffuse xerosis, hyperlinearity of palms, scales on legs,
      scalp desquamation and keratosis pilaris - and a global IV clinical severity
      score was derived (0-15). Age of onset of AD, SCORAD (SCORing of Atopic
      Dermatitis), family and personal history for other signs of atopy, and total
      immunoglobulin E were recorded. Genotyping was performed for R501X and 2282del4.
      Univariate and multivariate analysis for factors associated with AD or AD + IV
      were conducted. RESULTS: In univariate analysis, family history of atopy, global
      clinical severity scoring and 2282del4 FLG mutation were positively correlated
      with the AD + IV phenotype. Using multivariate analysis, SCORAD for AD (OR 0.94,
      P = 0.01) and global clinical severity scoring for AD + IV (OR 2.62, P < 0.0001)
      were found to be independent factors. CONCLUSIONS: The 2282del4 FLG mutation was
      confirmed as a good marker of early-onset disease. Moreover, our global clinical
      severity score yielded a good negative predictive value of common caucasian null
      FLG mutations.

PMID- 22612621
TI  - Activity-dependent modulation of gonadotrophin-releasing hormone neurone activity
      by acute oestradiol.
AB  - Oestradiol (E2) exerts potent feedback actions upon gonadotrophin-releasing
      hormone (GnRH) neurones and part of this feedback action may occur through the
      rapid action of E2. Using a transgenic GnRH-Pericam mouse line that allows real
      time intracellular calcium concentrations ([Ca2+](i)) to be monitored in adult
      GnRH neurones in a brain slice preparation, we examined the acute effects of 100
      pM-100 nM E2 on [Ca2+](i) transients in spontaneously active GnRH neurones.
      Approximately 30% of GnRH neurones exhibit spontaneous [Ca2+](i) transients at a
      frequency greater than two transients/15 min in adult female mice. In these
      cells, treatment with an incremental 1, 10, 100 nM E2 protocol or 100 pM E2 alone
      resulted in the suppression or complete cessation of [Ca2+](i) transients in 15
      of 18 (83%) GnRH neurones. This effect was mimicked by E2 bound to albumin,
      suggesting a membrane site of action, and was maintained in oestrogen receptor
      beta knockout mice, indicating that this receptor is not essential for the rapid
      suppression of [Ca2+](i) transients. These findings contrast with those GnRH
      neurones exhibiting very few or no [Ca2+](i) transients (< 2 transients/15 min)
      that exhibit the opposite response of being activated by acute E2. A series of
      dual calcium-cell-attached electrical recordings showed that [Ca2+](i) transients
      were associated with GnRH neurone burst firing and that E2 suppression or
      activation of [Ca2+](i) transients was mirrored by a depression or initiation of
      burst firing. Taken together, these studies demonstrate that the acute actions of
      E2 on GnRH neurones are critically dependent upon their pattern of burst firing.

PMID- 22612620
TI  - Pharmacokinetics of lansoprazole and its main metabolites after single
      intravenous doses in healthy Chinese subjects.
AB  - The aim of the study was to evaluate the pharmacokinetics (PK) of lansoprazole
      (LPZ) and its main metabolites 5'-hydroxy lansoprazole (HLPZ) and lansoprazole
      sulphone (LPZS) after single intravenous (i.v.) doses of LPZ in healthy Chinese
      subjects, and the relationship between the cytochrome P450 (CYP) 2C19 phenotypes
      and the plasma concentrations of LPZS at the time-points in the elimination phase
      of LPZ. Twelve subjects were given lansoprazole by i.v. infusion. Blood samples
      were collected at designated time points up to 24 h. Plasma concentrations of
      LPZ, HLPZ and LPZS were quantified by a selective and sensitive liquid
      chromatography-tandem mass spectrometric (LC-MS/MS) method. After single i.v.
      doses of 15, 30 and 60 mg LPZ, C(max) and area under the plasma concentration
      time curve (AUC(0-t)) of LPZ were 725 +/- 151, 1480 +/- 190, 3130 +/- 480 ug . L(
      1) and 1690 +/- 1210, 3630 +/- 2530, 8080 +/- 4550 ug . h . L(-1), respectively.
      LPZ was generally well tolerated in healthy Chinese subjects, and displayed
      linear PK in the range of 15-60 mg. There were significant differences in the
      elimination of LPZ and the formation of LPZS between the single CYP2C19 poor
      metabolizer (PM) and the CYP2C19 extensive metabolizers (EM). The concentration
      of LPZS at the time-points in the elimination phase of LPZ could be monitored for
      CYP2C19 phenotyping. As a probe drug for CYP2C19 phenotyping, LPZ for injection
      might be more suitable than LPZ oral formulations.

PMID- 22612619
TI  - Stereoselective and regiospecific hydroxylation of ketamine and norketamine.
AB  - The objective was to determine the cytochrome P450s (CYPs) responsible for the
      stereoselective and regiospecific hydroxylation of ketamine [(R,S)-Ket] to
      diastereomeric hydroxyketamines, (2S,6S;2R,6R)-HK (5a) and (2S,6R;2R,6S)-HK (5b)
      and norketamine [(R,S)-norKet] to hydroxynorketamines, (2S,6S;2R,6R)-HNK (4a),
      (2S,6R;2R,6S)-HNK (4b), (2S,5S;2R,5R)-HNK (4c), (2S,4S;2R,4R)-HNK (4d),
      (2S,4R;2R,4S)-HNK (4e), (2S,5R;2R,5S)-HNK (4f). The enantiomers of Ket and norKet
      were incubated with characterized human liver microsomes (HLMs) and expressed
      CYPs. Metabolites were identified and quantified using LC/MS/MS and apparent
      kinetic constants estimated using single-site Michaelis-Menten, Hill or substrate
      inhibition equation. 5a was predominantly formed from (S)-Ket by CYP2A6 and N
      demethylated to 4a by CYP2B6. 5b was formed from (R)- and (S)-Ket by CYP3A4/3A5
      and N-demethylated to 4b by multiple enzymes. norKet incubation produced 4a, 4c
      and 4f and minor amounts of 4d and 4e. CYP2A6 and CYP2B6 were the major enzymes
      responsible for the formation of 4a, 4d and 4f, and CYP3A4/3A5 for the formation
      of 4e. The 4b metabolite was not detected in the norKet incubates. 5a and 4b were
      detected in plasma samples from patients receiving (R,S)-Ket, indicating that 5a
      and 5b are significant Ket metabolites. Large variations in HNK concentrations
      were observed suggesting that pharmacogenetics and/or metabolic drug interactions
      may play a role in therapeutic response.

PMID- 22612623
TI  - Association of breastfeeding and adolescents' psychopathology: a large
      prospective study.
AB  - PURPOSE: There is little known about the association between breastfeeding and
      long-term child psychopathology. This study aimed to examine the impact of
      breastfeeding on child mental health and problem behavior at 14 years and whether
      this association is confounded by other variables. SUBJECTS AND METHODS: Data
      were from a pre-birth prospective study that included mothers and their children
      followed up from pregnancy to 14 years of the child's age in Brisbane, Australia.
      The child's anxiety/depression, withdrawal problems, somatic complaints, social
      problems, thought problems, attention problems, aggression, and delinquency were
      measured using the Achenbach Youth Self Report at 14 years. Breastfeeding was
      prospectively assessed at the 6-month follow-up of the study. The analysis was
      based on 4,502 adolescents who responded to the YSR questionnaire and for whom
      prospective data were available on breastfeeding. RESULTS: Breastfeeding as
      reported by mothers when the child was 6 months old predicted reduced symptoms of
      child mental health and problem behavior at 14 years. The impact of breastfeeding
      on the child's social problems, attention problems, and aggressive behavior
      remained statistically significant after controlling for the effect of other
      variables, such as unplanned pregnancy, maternal mental health, and substance use
      during pregnancy. CONCLUSIONS: Our data suggest that breastfeeding for at least 4
      months can have a significant protective effect on a child's social, attention,
      and aggression problems in early adolescence. Given the limitations of the
      existing evidence, further research is needed to investigate the robustness of
      the findings of this study and the mechanisms of long-term association between
      breastfeeding and reduced social, attention, and aggression problems of the
      offspring in adolescence.

PMID- 22612624
TI  - Use of electronic communication by physician breastfeeding experts for support of
      the breastfeeding mother.
AB  - BACKGROUND: Breastfeeding initiation and duration increase because of physician
      encouragement. However, many physicians have not received education on
      breastfeeding, and some may not have a supportive attitude or commitment to
      breastfeeding. Patients identify dissatisfaction with their current provider as a
      motivating factor in seeking health information on the Internet. This survey was
      performed to determine how many physicians with an interest and expertise in
      breastfeeding are being contacted for breastfeeding information over the Internet
      and to examine physicians' attitudes to these requests. SUBJECTS AND METHODS: An
      e-mail describing the survey, inviting participation, and containing a link to
      the online questionnaire was posted on the Web site of the Academy of
      Breastfeeding Medicine and as well as on the Listserv of the American Academy of
      Pediatrics-Section on Breastfeeding. Information collected included physician
      training, successes and challenges related to providing breastfeeding medicine
      support by e-mail, and current level of e-mail communication with patients
      regarding breastfeeding issues. RESULTS: One-fourth of physicians in our survey
      receive e-mails with questions about breastfeeding issues from patients with whom
      they have no preexisting relationships. More receive e-mail from known patients.
      This suggests that breastfeeding mothers seek expert information on the Internet.
      Over half of the physicians replied to e-mails individually and without any
      financial reimbursement. CONCLUSIONS: Many breastfeeding mothers reach out to
      breastfeeding experts over the Internet. Our findings suggest that physicians who
      provide care to breastfeeding mothers need further education on breastfeeding to
      provide adequate support to their own patients.

PMID- 22612622
TI  - Neuroaxonal regeneration is more pronounced in early multiple sclerosis than in
      traumatic brain injury lesions.
AB  - The extent of irreversible neuroaxonal damage is the key determinant of permanent
      disability in traumatic and inflammatory conditions of the central nervous system
      (CNS). Structural damage is nevertheless in part compensated by neuroplastic
      events. However, it is unknown whether the same kinetics and mechanisms of
      neuroaxonal de- and regeneration take place in inflammatory and traumatic
      conditions. We analyzed neuroaxonal degeneration and plasticity in early multiple
      sclerosis (MS) lesions and traumatic brain injury (TBI). Neuroaxonal degeneration
      identified by the presence of SMI31+ chromatolytic neurons and SMI32+ axonal
      profiles were characteristic features of leukocortical TBI lesions. Axonal
      transport disturbances as determined by amyloid precursor protein (APP)+
      spheroids were present in both TBI and MS lesions to a similar degree. Neurons
      expressing growth-associated protein 43 (GAP43) and synaptophysin (Syn) were
      found under both pathological conditions. However, axonal swellings
      immunopositive for GAP43 and Syn clearly prevailed in subcortical MS lesions,
      suggesting a higher regenerative potential in MS. In this context, GAP43+/APP+
      axonal spheroid ratios correlated with macrophage infiltration in TBI and MS
      lesions, supporting the idea that phagocyte activation might promote neuroplastic
      events. Furthermore, axonal GAP43+ and Syn+ swellings correlated with prolonged
      survival after TBI, indicating a sustained regenerative response.

PMID- 22612625
TI  - Infant and maternal factors influencing breastmilk sodium among primiparous
      mothers.
AB  - OBJECTIVE: This study identified birth events and infant/maternal factors related
      to breastmilk sodium (Na+) among primiparous mothers. SUBJECTS AND METHODS: Data
      were collected in a larger study on perceived insufficient milk among 252
      breastfeeding mothers at a Canadian, French-speaking university maternal care
      center. Birth events and infant and maternal factors were collected at 48 hours,
      2 weeks, and 6 weeks after birth and were analyzed with bivariate and regression
      analysis. RESULTS: Presence of gestational diabetes increases the risk of an
      elevated breastmilk Na+ level at 48 hours, and increased number of breastfeeds
      (mean=8.91, SD=3.77) lowers it, indicating lactogenesis II was initiated.
      CONCLUSIONS: Breastfeeding frequency impacts initiation of lactogenesis II, which
      in turn influences duration of breastfeeding exclusivity. Therefore feedings
      should be promoted as soon as possible after birth and as frequently as eight to
      12 times a day.

PMID- 22612626
TI  - A versatile scaffold for site-specific modification of cyclic tetrapeptides.
AB  - A novel scaffold that can be used to prepare conformationally homogeneous cyclic
      tetrapeptides equipped with a beta-amino acid residue is disclosed. It is shown
      that regioselective structural modification can be accomplished using thiols and
      azide nucleophiles, commonly associated with rich downstream chemistry. The
      method should find application in efforts to constrain privileged tripeptide
      sequences in rigid molecular scaffolds.

PMID- 22612627
TI  - Multifrequency EPR study of Fe3+ and Co2+ in the active site of desulforedoxin.
AB  - The understanding of the electronic structure of S > 1/2 transition-metal sites
      that show a large zero-field splitting (ZFS) of the magnetic sublevels benefits
      greatly from study by electron-paramagnetic-resonance (EPR) spectroscopy at
      frequencies above the standard 9.5 GHz. However, high-frequency EPR spectroscopy
      is technically challenging and still developing. Particularly the sensitivity of
      high-frequency EPR spectrometers is often too low to apply the technique in the
      study of transition-metal sites in proteins and enzymes. Here we report a
      multifrequency EPR study (at 9.5, 94.9, and 275.7 GHz) of the active site of the
      protein desulforedoxin, both in its natural Fe(3+) form and substituted with
      Co(2+). The 275.7 GHz EPR spectra made it possible to determine the ZFS
      parameters of the Fe(3+) site with high precision. No 275.7 GHz spectrum could be
      observed of the Co(2+) site, but based on 9.5 GHz spectra, its ZFS parameters
      could be estimated. We find that the typical variation in the geometry of the
      active site of a protein or enzyme, referred to as conformational strain, does
      not only make the detection of EPR spectra challenging, but also their analysis.
      Comparison of the EPR results on the active site of desulforedoxin to those of
      the closely related active site of rubredoxin illustrates the necessity of
      explicit quantum-chemical calculations in order to interrelate the electronic and
      geometric structure of biological transition-metal sites.

PMID- 22612628
TI  - Effect of listeners' linguistic background on perceptual judgements of
      hypernasality.
AB  - BACKGROUND: Many speech and language therapists work in a multilingual
      environment, making cross-linguistic studies of speech disorders clinically and
      theoretically important. AIMS: To investigate the effect of listeners' linguistic
      background on their perceptual ratings of hypernasality and the reliability of
      the ratings. METHODS & PROCEDURES: The speech samples were nine Cantonese non
      nasal sentences produced by 22 speakers (20 speakers with hypernasality and two
      speakers with normal resonance). Twenty-four non-expert listeners (twelve
      Cantonese and twelve English) rated the speech samples using direct magnitude
      estimation. OUTCOMES & RESULTS: The Cantonese listeners gave significantly higher
      ratings to the female speech samples (mean = 76.02) than the English listeners
      (mean = 59.24; t = 3.189, p<0.05). The difference in direct magnitude estimation
      ratings between the Cantonese (78.57) and English (70.83) listeners was not
      significant for the male samples (t = 2.097, p>0.05). Despite the difference in
      numerical ratings between the two groups of listeners, the high correlations
      between their ratings indicated that they ranked the speech samples in terms of
      hypernasality severity similarly. Both groups of listeners showed high inter
      judge reliability but low intra-judge reliability for rating the two sets of
      speech samples. There was a significant difference in intra-judge reliability
      between the Cantonese (r = 0.55) and English (r = 0.39) listeners for the male
      samples (t = 2.125, p<0.05). CONCLUSIONS: Generally, the non-expert Cantonese and
      English listeners ranked the Cantonese samples in terms of hypernasality in a
      similar way. The reliability of ratings by non-expert listeners was moderate. The
      need for further cross-linguistic studies into perceptual evaluations of speech
      disorders is highlighted.

PMID- 22612629
TI  - Role of auditory attention in the real-time processing of simple grammar by
      children with specific language impairment: a preliminary investigation.
AB  - BACKGROUND: This study investigates the effects of two dimensions of attentional
      functioning, sustained focus of attention and resource capacity/allocation, on
      the real-time processing of simple sentences by children with specific language
      impairment (SLI) and typically developing (TD) children matched for age. METHODS
      & PROCEDURES: Thirty-six school-age children with SLI and 36 age-matched TD peers
      completed an auditory continuous performance task (ACPT) as a measure of
      sustained attention, a concurrent verbal processing-storage task as a measure of
      resource capacity/allocation, and a word-recognition reaction time (RT) task
      (index of sentence processing). Correlation and regression analyses were run to
      determine the association between the two measures of attention and word
      recognition RT. OUTCOMES & RESULTS: Children with SLI were outperformed by the TD
      children on each of the tasks. For each group, scores on both the ACPT and
      concurrent processing-storage tasks significantly correlated with word
      recognition RT. The partial correlations (with the effects of age removed)
      remained significant, but only for the SLI group. Results of a regression
      analysis for the SLI group showed that age predicted 12.3% of unique variance in
      word recognition RT, while ACPT score accounted for an additional significant
      45.7% of unique variance and the processing-storage task score accounted for
      another significant 4.3% of unique variance. CONCLUSIONS: The real-time
      processing of simple grammar by children with SLI appears to involve significant
      use of sustained focus of attention and attentional resource capacity. In the
      case of TD children, however, neither sustained attention nor attentional
      resources appears to be significantly involved in simple sentence processing.

PMID- 22612630
TI  - Lexical access in children with and without specific language impairment: a cross
      modal picture-word interference study.
AB  - Two experiments examined the time course of lexical information availability in
      20 adults, 20 children (8;0-10;0) with typical language development, and in 20
      children (8;0-10;0) with specific language impairment. A cross-modal picture-word
      interference paradigm was used in which participants named the pictures as
      quickly as possible while ignoring the phonologically and semantically related
      interfering words. A novel early phonological interference effect appeared in all
      groups. Similar temporal patterns were revealed for the adults and the typical
      language development group, supporting the notion of similar underlying
      lexicalization mechanisms. Parametric differences were found in overall response
      times and errors, with children responding slower and producing more errors than
      adults. The presence of a phonological facilitation effect suggests that children
      with specific language impairment utilize phonological primes to ease lexical
      access. Children with specific language impairment exhibited lingering semantic
      inhibition and a late semantic inhibition effect suggesting difficulty in
      processing semantic information. Data from all participants support the cascaded
      processing model of lexical access.

PMID- 22612631
TI  - Contribution of phonological and broader language skills to literacy.
AB  - BACKGROUND: Recent models of reading ability propose that both phonological and
      broader language skills are important for the development of literacy. Whilst
      there are numerous studies that consider the role of phonological skills in
      literacy, fewer studies have considered the role of broader language skills and
      reading proficiency. AIMS: To examine how phonological skills and broader
      language skills relate to word reading (including speeded word reading), non-word
      reading, spelling, and reading comprehension. METHODS & PROCEDURES: Seventy-one
      children (mean age = 10.10; 21 girls) with a wide range of reading and language
      abilities took part in the study. A number of tasks were administered that
      measured phonological skills (phonological awareness, phonological short-term
      memory) and broader language skills (vocabulary, morphology, sentence correction,
      and sentence processing). OUTCOMES & RESULTS: In support of previous work, both
      phonological and broader language abilities predicted reading and spelling. The
      exception was the timed single-word-reading task that was influenced by
      vocabulary. Reading comprehension was solely predicted by broader language
      abilities. CONCLUSIONS: Both phonological and broader language abilities are
      involved in the development of reading and spelling, but in the case of reading
      comprehension, broader language skills are crucial.

PMID- 22612632
TI  - A diagnostically promising technique for tallying nominal reference errors in the
      narratives of school-aged children with foetal alcohol spectrum disorders (FASD).
AB  - BACKGROUND: Foetal Alcohol Spectrum Disorders (FASD) include the range of
      disabilities that occur in children exposed to alcohol during pregnancy, with
      Foetal Alcohol Syndrome (FAS) on the severe end of the spectrum. Clinical
      research has documented a range of cognitive, social, and communication deficits
      in FASD and it indicates the need for diagnostic tools that can identify children
      with diminished communicative capacities resulting from prenatal alcohol
      exposure. Previous research indicates that analysis of nominal reference errors
      within narrative discourse may provide such a tool. AIMS: To demonstrate the
      potential diagnostic utility of a new tool for tallying nominal reference errors
      in the oral narratives of school-aged children with FASD by presenting
      quantitative measurement data that address interrater agreement and predictive
      accuracy. METHODS & PROCEDURES: Retrospective analysis was conducted on
      spontaneously produced oral narratives from 32 school-aged children (8;5-11;7)
      with a range of socio-economic and ethnic profiles. Sixteen of the children had
      been previously diagnosis with an FASD, including five with full or partial FAS
      (pFAS). The remaining 16 children were considered typically developing (TD). A
      range of methods for calculating the rate of nominal reference errors (rNRE) were
      used to predict which narratives were produced by children from each group.
      Accuracy (sensitivity and specificity) for two predictions (FASD versus TD, and
      FAS/pFAS versus all others) was quantified using receiver-operating
      characteristic curve analyses. Pairwise statistical comparisons were made between
      methods to determine which had the most diagnostic potential. OUTCOMES & RESULTS:
      The proposed system for calculating the rNRE was highly accurate at predicting
      which narratives were produced by children with FASD (versus TD, 88% overall
      accuracy), and which were produced by children with FAS/pFAS (versus all others,
      97% overall accuracy), and outperformed all other methods tested. Agreement on
      coding decisions between independent judges was high (kappa = 0.90). CONCLUSIONS:
      The strong predictive accuracy demonstrated in this study provides empirical
      evidence that the system proposed in this feasibility study has sufficient
      sensitivity and diagnostic utility to warrant further development for use with
      children suspected of prenatal alcohol exposure. It also points to the potential
      for the tool to be used with other clinical populations that, even in the absence
      of a confirmed alcohol exposure, share many of the communication challenges of
      this complex clinical population.

PMID- 22612633
TI  - "Face-lifting" and "make-up" for microorganisms: layer-by-layer polyelectrolyte
      nanocoating.
AB  - Layer-by-layer encapsulation of living biological cells and other microorganisms
      via sequential adsorption of oppositely charged functional nanoscale components
      is a promising instrument for engineering cells with enhanced properties and
      artificial microorganisms. Such nanoarchitectural shells assembled in mild
      aqueous conditions provide cells with additional abilities, widening their
      functionality and applications in artificial spore formation, whole-cell
      biosensors, and fabrication of three-dimensional multicellular clusters.

PMID- 22612634
TI  - Using individual differences to predict job performance: correcting for direct
      and indirect restriction of range.
AB  - The present study investigates the relationship between individual differences,
      indicated by personality (FFM) and general mental ability (GMA), and job
      performance applying two different methods of correction for range restriction.
      The results, derived by analyzing meta-analytic correlations, show that the more
      accurate method of correcting for indirect range restriction increased the
      operational validity of individual differences in predicting job performance and
      that this increase primarily was due to general mental ability being a stronger
      predictor than any of the personality traits. The estimates for single traits can
      be applied in practice to maximize prediction of job performance. Further,
      differences in the relative importance of general mental ability in relation to
      overall personality assessment methods was substantive and the estimates provided
      enables practitioners to perform a correct utility analysis of their overall
      selection procedure.

PMID- 22612635
TI  - Transient hydrops fetalis in a prenatally diagnosed pentasomy X?
AB  - Numerical abnormalities of sex chromosomes are seen approximately 1 in 400 live
      births. Pentasomy X is a very rare chromosomal abnormality and it is defined as
      presence of five X chromosomes instead of two. Prenatal sonographic features have
      rarely been described in the literature before. Here we present a non-immune
      fetal hydrops diagnosed during the 17th week of gestation. Ultrasonographic
      examination revealed subcutaneous edema, pleural effusion and ascites, and also
      clinodactyly of the fifth fingers of both hands. The fetal karyotype was assessed
      as 49,XXXXX (pentasomy X) in two different culture flasks. Hydropic signs
      regressed at 21 weeks' gestation. Prenatal diagnosis may not be possible usually
      for this rare chromosomal abnormality. Every anomaly detected prenatally, such as
      transient hydrops, may help us to diagnose pentasomy X.

PMID- 22612637
TI  - Subungual verrucous carcinoma with bone invasion.

PMID- 22612636
TI  - Low BMI at age 20 years predicts gestational diabetes independent of BMI in early
      pregnancy in Japan: Tanaka Women's Clinic Study.
AB  - AIMS: Maternal obesity and weight gain since early adulthood are known predictors
      of gestational diabetes in Western countries. However, their impact has not been
      evaluated well in Asia, where mean BMI levels are generally lower than in Western
      countries. We therefore examined the associations of BMI at age 20 years and BMI
      change since age 20 years with the risk of gestational diabetes in Japanese
      pregnant women. METHODS: Six hundred and twenty-four consecutive pregnant women
      without recognized diabetes before pregnancy, whose initial obstetric clinic
      visit was before 13 weeks' gestation, were prospectively observed. Weight at age
      20 years was self-reported. Baseline height and weight measurements were obtained
      at the initial obstetric visit. Multivariate logistic regression analysis
      estimated the risk of incident gestational diabetes for BMI change since 20 years
      and BMI at age 20 years. RESULTS: Twenty-eight women developed incident
      gestational diabetes. By multivariate logistic regression analysis that adjusted
      for maternal age, parity and baseline BMI, we observed a statistically
      significant inverse association between BMI at age 20 years and incidence of
      gestational diabetes (odds ratio 0.68, 95% CI 0.51-0.92). Similarly, when we
      assessed the association of BMI change since age 20 years, adjusted for maternal
      age and parity, BMI change was associated with an increased risk of gestational
      diabetes (odds ratio 1.26, 95% CI 1.03-1.53). When we focused on the threshold of
      risk of gestational diabetes, women with BMI at 20 years of less than 18 kg/m(2)
      had a 6.30-fold (2.26-17.59) greater risk than women with both BMI at age 20
      years of 18 kg/m(2) or more and BMI change since age 20 years of less than 1.85.
      CONCLUSIONS: Both low BMI at age 20 years and BMI change since age 20 years were
      significantly associated with increased risk of incident gestational diabetes.

PMID- 22612638
TI  - Feline exocrine pancreatic carcinoma: a retrospective study of 34 cases.
AB  - Thirty-four cases were reviewed in this retrospective study for information on
      clinical presentation, prognostic indicators, survival time and response to
      various therapies. The most common presenting clinical signs were weight loss,
      decreased appetite, vomiting, palpable abdominal mass and diarrhoea. Metastatic
      disease was confirmed in 11 cats. The overall median survival was 97 days. The
      median survival times for patients who received chemotherapy or had their masses
      surgically removed was 165 days. Those patients who had an abdominal effusion
      present at the time of diagnosis survived a median of 30 days. Cats that received
      non-steroidal anti-inflammatory drug therapy had a median survival of 26 days.
      This study confirms that exocrine pancreatic carcinoma in cats is an aggressive
      tumour with a high metastatic rate and poor prognosis, although three patients
      survived over 1 year. Fifteen percent of the patients were diabetic, which raises
      the question as to what the link between diabetes and pancreatic cancer in people
      and cats may be. 

PMID- 22612639
TI  - Nighttime intensivist staffing and mortality among critically ill patients.
AB  - BACKGROUND: Hospitals are increasingly adopting 24-hour intensivist physician
      staffing as a strategy to improve intensive care unit (ICU) outcomes. However,
      the degree to which nighttime intensivists are associated with improvements in
      the quality of ICU care is unknown. METHODS: We conducted a retrospective cohort
      study involving ICUs that participated in the Acute Physiology and Chronic Health
      Evaluation (APACHE) clinical information system from 2009 through 2010, linking a
      survey of ICU staffing practices with patient-level outcomes data from adult ICU
      admissions. Multivariate models were used to assess the relationship between
      nighttime intensivist staffing and in-hospital mortality among ICU patients, with
      adjustment for daytime intensivist staffing, severity of illness, and case mix.
      We conducted a confirmatory analysis in a second, population-based cohort of
      hospitals in Pennsylvania from which less detailed data were available. RESULTS:
      The analysis with the use of the APACHE database included 65,752 patients
      admitted to 49 ICUs in 25 hospitals. In ICUs with low-intensity daytime staffing,
      nighttime intensivist staffing was associated with a reduction in risk-adjusted
      in-hospital mortality (adjusted odds ratio for death, 0.62; P=0.04). Among ICUs
      with high-intensity daytime staffing, nighttime intensivist staffing conferred no
      benefit with respect to risk-adjusted in-hospital mortality (odds ratio, 1.08;
      P=0.78). In the verification cohort, there was a similar relationship among
      daytime staffing, nighttime staffing, and in-hospital mortality. The interaction
      between nighttime staffing and daytime staffing was not significant (P=0.18), yet
      the direction of the findings were similar to those in the APACHE cohort.
      CONCLUSIONS: The addition of nighttime intensivist staffing to a low-intensity
      daytime staffing model was associated with reduced mortality. However, a
      reduction in mortality was not seen in ICUs with high-intensity daytime staffing.
      (Funded by the National Heart, Lung, and Blood Institute.).

PMID- 22612640
TI  - Intensive enough?

PMID- 22612641
TI  - Pulmonary hydatid cyst: The characteristics of patients and diagnostic efficacy
      of bronchoscopy.
AB  - BACKGROUND AND OBJECTIVES: Pulmonary hydatid cyst (PHC) is a parasitic
      infestation caused by larvae of Echinococcus granulosus. The lung is the most
      commonly involved organ after the liver. There is lack of enough data on the
      efficacy of bronchoscopy in patients with PHC, and the diagnostic usefulness of
      bronchoscopy is still controversial. We aimed to present the diagnostic efficacy
      of bronchoscopy and disease characteristics of patients with PHC. METHODS: PHC
      was diagnosed in 72 patients--51% of patients in Group I (uncomplicated PHC) and
      49% of patients in Group II (complicated PHC)--in Dr Suat Seren Education and
      Research Hospital for Chest Diseases and Thoracic Surgery. The data of patients
      including age, gender, symptoms, and radiological, bronchoscopic,
      microbiological, and pathological findings were retrospectively evaluated.
      RESULTS: The bronhoscopic findings were defined as hyperemia (44%), normal (38%),
      edema (32%), purulent secretion (24%), external bronchial compression (24%), and
      endobronchial cyst membrane (21%), respectively. Cyst membranes were seen during
      bronchoscopy in 7 (20.5%) of the patients and 6 (86%) of them were in Group II.
      Hydatoptosis (expectoration of cyst contents), cough, hemoptysis, leukocytosis,
      Echinecoccus IgG positivity, chest pain, and fever were significantly higher in
      Group II. According to radiological images, the multiple cystic nodular lesions
      and well-shaped cystic nodular lesions were significantly higher in Group I.
      However, water-lily sign, images of abscess, and pneumonic infiltration were
      significantly higher in Group II. CONCLUSION: The diagnosis of PHC is usually
      made with the combination of clinical, radiological, serological, and surgical
      procedures. We suggest that the fiberoptic bronchoscopy can be used as a
      diagnostic method, especially in complicated PHC.

PMID- 22612642
TI  - Methyl 2,2-difluoro-2-(fluorosulfonyl)acetate, a difluorocarbene reagent with
      reactivity comparable to that of trimethylsilyl 2,2-difluoro-2
      (fluorosulfonyl)acetate (TFDA).
AB  - Under specific high concentration, high temperature conditions, methyl 2,2
      difluoro-2-(fluorosulfonyl)acetate (MDFA) has been found to act as a very
      efficient source of difluorocarbene, exhibiting carbene reactivity
      characteristics comparable to those exhibited by trimethylsilyl 2,2-difluoro-2
      (fluorosulfonyl)acetate (TFDA). For example, in reaction with highly unreactive n
      butyl acrylate and using only 2 equiv of MDFA, a yield of 76% of
      difluorocyclopropane product was obtained after 2 days.

PMID- 22612643
TI  - Cartography of cell morphology in tomato pericarp at the fruit scale.
AB  - In fleshy fruits, the variability of cell morphology at the fruit scale is
      largely unknown. It presents both a huge variability and a high level of
      organization. Better knowledge of cell morphology heterogeneity within the fruit
      is necessary to understand fruit development, to model fruit mechanical
      behaviour, or to investigate variations of physico-chemical measurements. A
      generic approach is proposed to build cartographies of cell morphology at the
      fruit scale, which depict regions corresponding to different cell morphologies.
      The approach is based on: (1) sampling the whole fruit at known positions; (2)
      imaging and quantifying local cell morphology; (3) pooling measurements to take
      biological variability into account and (4) projecting results in a morphology
      model of the whole fruit. The result is a synthetic representation of cell
      morphology variations within the whole fruit. The method was applied to the
      characterization of cell morphology in tomato pericarp. Two different imaging
      scales that provided complementary descriptions were used: 3D confocal microscopy
      and macroscopy. The approach is generic and can be adapted to other fruits or
      other products.

PMID- 22612644
TI  - Nature's polyoxometalate chemistry: X-ray structure of the Mo storage protein
      loaded with discrete polynuclear Mo-O clusters.
AB  - Some N(2)-fixing bacteria prolong the functionality of nitrogenase in molybdenum
      starvation by a special Mo storage protein (MoSto) that can store more than 100
      Mo atoms. The presented 1.6 A X-ray structure of MoSto from  Azotobacter
      vinelandii  reveals various discrete polyoxomolybdate clusters, three covalently
      and three noncovalently bound Mo(8), three Mo(5-7), and one Mo(3) clusters, and
      several low occupied, so far undefinable clusters, which are embedded in specific
      pockets inside a locked cage-shaped (alphabeta)(3) protein complex. The
      structurally identical Mo(8) clusters (three layers of two, four, and two MoO(n)
      octahedra) are distinguishable from the [Mo(8)O(26)](4-) cluster formed in acidic
      solutions by two displaced MoO(n) octahedra implicating three kinetically labile
      terminal ligands. Stabilization in the covalent Mo(8) cluster is achieved by Mo
      bonding to Hisalpha156-N(epsilon2) and Glualpha129-O(epsilon1). The absence of
      covalent protein interactions in the noncovalent Mo(8) cluster is compensated by
      a more extended hydrogen-bond network involving three pronounced histidines. One
      displaced MoO(n) octahedron might serve as nucleation site for an inhomogeneous
      Mo(5-7) cluster largely surrounded by bulk solvent. In the Mo(3) cluster located
      on the 3-fold axis, the three accurately positioned His140-N(epsilon2) atoms of
      the alpha subunits coordinate to the Mo atoms. The formed polyoxomolybdate
      clusters of MoSto, not detectable in bulk solvent, are the result of an interplay
      between self- and protein-driven assembly processes that unite inorganic
      supramolecular and protein chemistry in a host-guest system. Template,
      nucleation/protection, and catalyst functions of the polypeptide as well as
      perspectives for designing new clusters are discussed.

PMID- 22612645
TI  - Economic consequences of the demography of MRSA patients and the impact of broad
      spectrum antimicrobials.
AB  - BACKGROUND: Studies have determined the societal impact of methicillin-resistant
      Staphylococcus aureus (MRSA) by modelling its impact on labour supply and
      productivity. In addition, most of the studies on the topic conclude that the
      problem of resistance should be counteracted on the macro level by reducing
      overall antibacterial consumption. OBJECTIVE: Two major questions have been
      raised in the present work. Firstly, is MRSA impairing labour supply and
      productivity? Secondly, is it the overall use of antibacterials that may be seen
      as crucial to the spread of MRSA infections? METHODS: The age distribution of
      MRSA patients is compared with the age distribution of the entire patient
      population at a German teaching hospital. In addition, the age distribution of
      MRSA patients was applied to the age distribution of the German population in the
      year 2050 in order to identify the effects of the double-ageing process on the
      spread of MRSA. Furthermore, recent epidemiological studies were reviewed on the
      impact of overall antibacterial consumption on MRSA infection rates. RESULTS:
      Based on available data, we show that patients infected or colonized with MRSA
      are, for the most part, beyond retirement age and thus not responsible for
      changes in labour supply or productivity. Application of age distribution of MRSA
      patients to the age distribution of the German population in the year 2050 gives
      a 24% increase in the number of MRSA cases to a total of 182 778 due to an ageing
      population. In addition, we show that a 32% reduction in the cost of MRSA to the
      German healthcare system could be reached if use of fluoroquinolones and third
      generation cephalosporins was reduced by just 10% and, correspondingly, use of
      antiseptics for hand disinfection was increased by 10%. CONCLUSIONS: MRSA is a
      phenomenon that, to a larger degree, affects the elderly population rather than
      the labour force. When it comes to policy options to counteract MRSA on the macro
      level, most economic research on the topic is biased in assuming that the overall
      use of antibacterials is responsible for the spread of MRSA infections.

PMID- 22612646
TI  - Optimizing the use of the AUDIT for alcohol screening in college students.
AB  - The screening and brief intervention modality of treatment for at-risk college
      drinking is becoming increasingly popular. A key to effective implementation is
      use of validated screening tools. Although the Alcohol Use Disorders
      Identification Test (AUDIT) has been validated in adult samples and is often used
      with college students, research has not yet established optimal cutoff scores to
      screen for at-risk drinking. Four hundred and one current drinkers completed
      computerized assessments of demographics, family history of alcohol use
      disorders, alcohol use history, alcohol-related problems, and general health. Of
      the 401 drinkers, 207 met criteria for at-risk drinking. Receiver operating
      characteristic (ROC) curve analysis revealed that the area under the ROC (AUROC)
      of the AUDIT was .86 (95% CI [.83, .90]). The first 3 consumption items of the
      AUDIT (AUDIT-C; AUROC = .89, 95% CI [.86, .92]) performed significantly better
      than the AUDIT in the detection of at-risk drinking in the whole sample, and
      specifically for females. Gender differences emerged in the optimal cutoff scores
      for the AUDIT-C. A total score of 7 should be used for males, and a score of 5
      should be used for females. These empirical guidelines may enhance identification
      of at-risk drinkers in college settings.

PMID- 22612647
TI  - Comparing the MMPI-2 scale scores of parents involved in parental competency and
      child custody assessments.
AB  - MMPI-2 scores from a parent competency sample (N = 136 parents) are compared with
      a previously published data set of MMPI-2 scores for child custody litigants (N =
      508 parents; Bathurst et al., 1997). Independent samples t tests yielded
      significant and in some cases substantial differences on the standard MMPI-2
      clinical scales (especially Scales 4, 8, 2, and 0), with the competency sample
      obtaining higher clinical scores as well as higher scores on F, FB, VRIN, TRIN,
      and L, but lower scores on K, relative to the custody sample. Despite the higher
      scores in the competency sample, MMPI-2 mean scores did not exceed the clinical
      cutoff (T > 65). Moreover, the present competency sample essentially replicates
      the MMPI-2 scores of a previously published competency sample, suggesting that
      the present findings are representative of that population. The present findings
      suggest that separate reference groups be used when conducting child custody vs.
      parental competency evaluations, as these appear to be distinct populations
      despite there being similarities in the testing circumstances.

PMID- 22612648
TI  - Factor structure of the Comprehensive Trail Making Test in children and
      adolescents with brain dysfunction.
AB  - The Comprehensive Trail Making Test (CTMT) is a relatively new version of the
      Trail Making Test that has a number of appealing features, including a large
      normative sample that allows raw scores to be converted to standard T scores
      adjusted for age. Preliminary validity information suggests that CTMT scores are
      sensitive to brain injury and demonstrate expected correlations with other
      neuropsychological tests, although the evidence also suggests that the factor
      structure of the CTMT may differ in children with brain dysfunction in comparison
      to the standardization sample. The present study addresses this matter by
      conducting a confirmatory factor analysis (CFA) of the CTMT in 382 children and
      adolescents. Of the 382, 191 were diagnosed with various forms of brain
      dysfunction, including 140 who had sustained a traumatic brain injury. The other
      191 participants were healthy controls who were individually matched on age and
      gender to the clinical group with brain dysfunction. Results of the CFA indicated
      that for the clinical group, a 2-factor model composed of Simple Sequencing and
      Complex Sequencing/Shifting factors provided the best fit for the data. Although
      these 2 factors were also identified in the controls, differences in pattern of
      loadings were present. Results suggest that the presence of brain dysfunction may
      alter the factor structure of the CTMT in children and adolescents.

PMID- 22612650
TI  - An examination of the Dirty Dozen measure of psychopathy: a cautionary tale about
      the costs of brief measures.
AB  - Given substantial interest in the traits conceived of as part of the "Dark Triad"
      -psychopathy, narcissism, and Machiavellianism--assessment of these traits is of
      great importance. The Dirty Dozen (DD; Jonason & Webster, 2010) is a brief
      measure of the Dark Triad constructs that uses 4 items to assess each of these
      constructs. In the present study, the authors examined the adequacy of the DD's
      Psychopathy scale by comparing it with established measures of psychopathy in a
      sample of undergraduates (Sample 1: N = 789) and male prisoners (Sample 2: N =
      75). DD's Psychopathy subscale manifested significant correlations with
      established measures, but the correlations were smaller than those evinced by the
      existing scales. The results also demonstrated that there is important variance
      related to interpersonal antagonism and disinhibition that is not assessed by the
      DD. The authors suggest that caution should be used in relying on the DD as a
      measure of psychopathy.

PMID- 22612649
TI  - The correspondence of daily and retrospective PTSD reports among female victims
      of sexual assault.
AB  - Research addressing the association between daily and retrospective symptom
      reports suggests that retrospective reports are typically inflated. The present
      study examined the association between daily posttraumatic stress disorder (PTSD)
      symptom reports over 1 month and a corresponding retrospective report (PTSD
      Checklist [PCL]; Weathers et al., 1993) for both total scores and symptom
      clusters. The authors hypothesized that greater PTSD symptom instability and
      greater depression would be associated with poorer agreement between daily and
      retrospective reports. Data were collected from 132 female college students who
      were sexually assaulted. Multilevel modeling indicated very strong agreement
      between mean daily and retrospective reports for total scores and symptom
      clusters, with pseudo-R2 ranging from .55 to .77. Depression symptoms did not
      moderate this association, but daily-retrospective agreement was lowest for the
      avoidance cluster, which was also the most unstable. Finally, retrospective
      recall for each symptom cluster showed acceptable specificity to the
      corresponding daily symptom clusters. Overall, these findings suggest that
      retrospective memories for global PTSD symptoms and symptom clusters, as assessed
      by the PCL, are consistent with daily reports over a 1-month period. Implications
      for clinical assessment methodology are discussed.

PMID- 22612651
TI  - Construction of a self-complexity scale for adolescents.
AB  - The goal of this article was to develop and validate a self-complexity scale for
      adolescents. Therefore, 4 empirical studies were developed. In Study 1, a content
      analysis of attributes used in school books was conducted. This analysis was
      complemented in Study 2 with an exploratory study of adolescent's self
      descriptions in an open-ended questionnaire (N = 67). From this, a set of 42
      attributes were identified. In Study 3, attributes' relevance and valence was
      evaluated by 109 adolescents, and a final set of 32 attributes was identified for
      the new scale. In Study 4, the Self-Complexity Scale for Adolescents (SCSA) was
      administered to a sample of 174 adolescents (aged 12-16), and SCSA structure,
      psychometric properties and correlation with self-esteem, as well as age and
      gender differences were analyzed. The research findings suggest that SC is a
      bidimensional construct and that SCSA is a reliable instrument. Furthermore,
      negative correlations were found between total and negative SC and self-esteem
      scores (convergent validity). Age differences were found in negative SC scores,
      with adolescents aged 14-16 exhibiting higher scores than 12- to 14-year-olds.

PMID- 22612653
TI  - Reduced high-molecular-weight adiponectin is an independent risk factor for
      cardiovascular lesions in hypercholesterolaemic patients.
AB  - BACKGROUND: The hormone adiponectin (APN) circulates in plasma as various
      multimeric complexes. The high-molecular-weight (HMW) isoform has been reported
      to exert the most favourable metabolic regulatory and vasculoprotective effects.
      This study determined the circulatory distribution of APN multimers and their
      relationships with cardiovascular disease (CVD)-related biochemical indicators in
      patients with hypercholesterolaemia (HC). METHODS: A total of 148 male age- and
      BMI-matched patients with HC (80 with CVD and 68 without CVD) and 84 male healthy
      controls were enrolled. Diabetes mellitus, hypertension, nephropathy and
      cigarette use constituted exclusion criteria. RESULTS: Both HMW and medium
      molecular-weight (MMW) forms of APN were significantly increased in HC without
      CVD (HMW: 4.98 +/- 0.87 vs 2.51 +/- 0.33 in control, P < 0.01; MMW: 2.20 +/- 0.36
      vs 1.01 +/- 0.15 in control, P < 0.01) and were comparable to control in patients
      with hypercholesterolaemia with CVD (HCVD). In comparison with other APN
      oligomers, HMW is most closely associated with the HCVD-related biochemical
      factors, total cholesterol (r = 0.345, P < 0.05), high-density lipoprotein
      cholesterol (HDLc, r = 0.325, P < 0.05) and uric acid (UA, r = -0.472, P < 0.01).
      Additional analysis via binary logistic regression suggests that HMW is an
      independent predictor of risk of HCVD (OR, 8.434; P = 0.018). CONCLUSION: These
      results suggest that reduced HMW isoform concentrations might be considered as an
      independent risk factor for cardiovascular complications in patients with HC.

PMID- 22612652
TI  - Antitumor agents. 293. Nontoxic dimethyl-4,4'-dimethoxy-5,6,5',6'
      dimethylenedioxybiphenyl-2,2'-dicarboxylate (DDB) analogues chemosensitize
      multidrug-resistant cancer cells to clinical anticancer drugs.
AB  - Novel dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylenedioxybiphenyl-2,2'
      dicarboxylate (DDB) analogues were designed and synthesized to improve their
      chemosensitizing action on KBvin (vincristine-resistant nasopharyngeal carcinoma)
      cells, a multidrug resistant cell line overexpressing P-glycoprotein (P-gp).
      Structure-activity relationship analysis showed that aromatic and bulky aliphatic
      side chains at the 2,2'-positions effectively and significantly sensitized P-gp
      overexpressing multidrug resistant (MDR) cells to anticancer drugs, such as
      paclitaxel (TAX), vincristine (VCR), and doxorubicin (DOX). DDB derivatives 16
      and 23 showed 5-10 times more effective reversal ability than verapamil (VRP) for
      TAX and VCR. Analogue 6 also exhibited five times greater chemosensitizing effect
      against DOX than VRP. Importantly, no cytotoxicity was observed by the active DDB
      analogues against both non-MDR and MDR cells, suggesting that DDB analogues serve
      as novel lead compounds for the development of chemosensitizers to overcome the
      MDR phenotype. The mechanism of action studies demonstrated that effective
      inhibition of P-glycoprotein by DDB analogues dramatically elevated the cellular
      concentration of anticancer drugs.

PMID- 22612654
TI  - Incomplete endothelialization of left atrial appendage occlusion device 10 months
      after implantation.
AB  - We describe the case of a 74-year-old man with Rendu Osler Weber syndrome
      affected by permanent atrial fibrillation, who underwent percutaneous placement
      of a 24-mm Watchman left atrial appendage system. After anticoagulation therapy
      dismissal, he had a transient ischemic attack (TIA). Therefore he underwent
      surgical removal of the device, ablation of atrial fibrillation with Maze IV
      procedure and biatrial reduction. Very interestingly, no significant
      endothelialization of the device was observed 10 months after implantation. In
      conclusion, this case is important because, to our knowledge, it is the first
      finding of Watchman device with lack of endothelialization.

PMID- 22612655
TI  - Complementary fluorescence and phosphorescence study of the interaction of
      brompheniramine with human serum albumin.
AB  - Binding of the antihistamine drug brompheniramine (BPA) to human serum albumin
      (HSA) is studied by measuring quenching of the fluorescence and room temperature
      phosphorescence (RTP) of tryptophan. The modified Stern-Volmer equation was used
      to derive association constants and accessible fractions from the steady-state
      fluorescence data. Decay associated spectra (DAS) revealed three tryptophan
      fluorescence lifetimes, indicating the presence of three HSA conformations. BPA
      causes mainly static quenching of the long-living, solvent-exposed conformer. RTP
      spectra and lifetimes, recorded under deoxygenated conditions in the presence of
      0.2 M KI, provided additional kinetic information about the HSA-BPA interactions.
      Fluorescence DAS that were also recorded in the presence of 0.2 M KI revealed
      that the solvent-exposed conformer is the major contributor to the RTP signal.
      The phosphorescence quenching is mostly dynamic at pH 7 and mostly static at pH
      9, presumably related to the protonation state of the alkylamino chain of BPA.
      This provides direct insight into the binding mode of the antihistamine drug, as
      well as kinetic information at both the nanosecond and the millisecond time
      scales.

PMID- 22612656
TI  - A capillary electrophoresis sequencing method for the identification of mutations
      in the inverted terminal repeats of adeno-associated virus.
AB  - Inverted terminal repeat (ITR) integrity is critical for the replication,
      packaging, and transduction of recombinant adeno-associated virus (rAAV), a
      promising gene therapy vector. Because AAV ITRs possess 70% GC content and are
      palindromic, they are notoriously difficult to sequence. The purpose of this work
      was to develop a reliable ITR sequencing method. The ITRs of two molecular clones
      of AAV2, pTZAAV and pAV2, were (1) sequenced directly from plasmid DNA in the
      presence of denaturant (direct sequencing method, DSM) or (2) first amplified in
      a reaction in which 7-deaza-dGTP was substituted for dGTP and the resultant
      amplification product sequenced (amplification sequencing method, ASM). The DSM
      and ASM techniques yielded clear chromatograms, read through the ITR hairpin, and
      revealed hitherto unreported mutations in each ITR. pTZAAV and pAV2 possess
      identical mutations at the upstream MscI site of the 5' ITR (T>G, nt 2) and the
      downstream MscI site of the 3' ITR (del. nt 4672-4679). The chromatograms for
      pAV2 also revealed that the ITRs of this construct were arranged in a FLOP/FLOP
      orientation. In addition, the DSM was successfully employed to recover ITR
      chromosomal junction sequences from a variety of rAAV-transduced tissue types.
      Both the DSM and ASM can be employed to sequence through the AAV ITR hairpin, and
      both techniques reliably detect mutations in the ITR. Because the DSM and ASM
      offer a way to verify ITR integrity, they constitute powerful tools for the
      process development of rAAV gene therapy.

PMID- 22612657
TI  - Specific targeting of human interleukin (IL)-13 receptor alpha2-positive cells
      with lentiviral vectors displaying IL-13.
AB  - The ability to selectively and efficiently target transgene delivery to specific
      cell types in vitro and in vivo remains one of the formidable challenges in gene
      therapy. Lentiviral vectors have several advantages that make them attractive as
      gene delivery vehicles and their tropism can be altered through pseudotyping,
      allowing transgene delivery to specific populations of cells. The human
      interleukin-13 receptor alpha2 (IL-13Ralpha2) is uniquely overexpressed in many
      different human tumors, making it an attractive target for cancer therapy. In
      this study, we examined whether IL-13Ralpha2-positive tumor cells can be
      specifically targeted with lentiviral vector pseudotypes containing a truncated
      fusion (F) protein derived from measles virus (MV) and a tail-truncated and
      receptor-blind MV hemagglutinin (H) protein bearing IL-13 at the C terminus. The
      retargeted lentiviral vector efficiently transduced cells that express high
      levels of IL-13Ralpha2, but not cells expressing low levels of IL-13Ralpha2 in
      vitro. In vivo, it specifically targeted IL-13Ralpha2-positive glioma cell
      xenografts in immunodeficient mice in the context of subcutaneous and
      intracranial glioma models. Similar lentiviral vectors may be developed for
      targeting other tumors expressing specific cell surface receptors.

PMID- 22612658
TI  - The human milk project: a quality improvement initiative to increase human milk
      consumption in very low birth weight infants.
AB  - OBJECTIVE: Human milk has well-established health benefits for preterm infants.
      We conducted a multidisciplinary quality improvement effort aimed at providing at
      least 500 mL of human milk/kg in the first 14 days of life to very low birth
      weight (VLBW) (< 1,500 g) infants in the neonatal intensive care unit. SUBJECTS
      AND METHODS: Improvement activities included antenatal consults with at-risk
      mothers, staff and parent education, a breast pump loaner program for
      uninsured/underinsured mothers, pump logs, establishment of a donor milk program,
      and twice-daily physician evaluation of infants' ability to tolerate feedings.
      RESULTS: The number of infants receiving at least 500 mL of human milk/kg in
      their first 14 days of life increased from 50% to 80% within 11 months of
      implementation, and this increase has been sustained for 4 years. Infants who met
      the feeding goal because they received donor milk increased each year. Since
      September 2007, infants have received, on average, 1,111 mL of human milk/kg.
      Approximately 4% of infants did not receive any human milk. Respiratory
      instability was the most frequent physiological reason given by clinicians for
      not initiating or advancing feedings in the first 14 days of life. CONCLUSIONS:
      Our quality improvement initiative resulted in a higher consumption of human milk
      in VLBW infants in the first 14 days of life. Other clinicians can use these
      described quality improvement methods and techniques to improve their VLBW
      babies' consumption of human milk.

PMID- 22612659
TI  - In situ nanomechanical measurements of interfacial strength in membrane-embedded
      chemically functionalized Si microwires for flexible solar cells.
AB  - Arrays of vertically aligned Si microwires embedded in polydimethylsiloxane
      (PDMS) have emerged as a promising candidate for use in solar energy conversion
      devices. Such structures are lightweight and concurrently demonstrate competitive
      efficiency and mechanical flexibility. To ensure reliable functioning under
      bending and flexing, strong interfacial adhesion between the nanowire and the
      matrix is needed. In situ uniaxial tensile tests of individual, chemically
      functionalized, Si microwires embedded in a compliant PDMS matrix reveal that
      chemical functionality on Si microwire surfaces is directly correlated with
      interfacial adhesion strength. Chemical functionalization can therefore serve as
      an effective methodology for accessing a wide range of interfacial adhesion
      between the rigid constituents and the soft polymer matrix; the adhesion can be
      quantified by measuring the mechanical strength of such systems.

PMID- 22612661
TI  - Intraoperative cell salvage in radical prostatectomy does not appear to increase
      long-term biochemical recurrence, metastases, or mortality.
AB  - BACKGROUND: Blood management strategies help to conserve allogeneic red blood
      cells, a finite resource. Intraoperative cell salvage (ICS) is an effective
      method of allogeneic avoidance. However, concerns persist about the safety of ICS
      in surgical oncology cases, including radical prostatectomy (RP). Previous
      findings do not support these concerns. We hypothesized that ICS would not
      increase rates of long-term prostate cancer recurrence characterized by
      biochemical failure, disease dissemination, or mortality. STUDY DESIGN AND
      METHODS: Consecutive patients undergoing RP by a single urologist over two 3
      month periods 1 year apart were analyzed retrospectively. Patients in the first
      period had preoperative autologous donation (PAD) but not ICS (PAD group),
      whereas those in the second period had ICS only (ICS group). Variables assessed
      included patient demographics, prostate-specific antigen levels at surgery and
      end of follow-up, clinical stage, operative time, surgical margin status,
      pathologic stage and grade, Gleason score sum, length of hospital stay,
      biochemical recurrence, metastases, and mortality. RESULTS: A total of 116
      consecutive patients were analyzed. Of these, 32 patients in the PAD group and 42
      patients in the ICS group had follow-up of at least 4.75 years. There was a
      significantly higher rate of biochemical failure (34.4% vs. 9.5%; p = 0.02) and
      metastases (12.5% vs. 0%; p = 0.03) in the PAD group versus the ICS group; there
      was no significant difference in mortality (9.4% vs. 0%; p = 0.08). CONCLUSION:
      ICS appears to be a safe and effective method of allogeneic blood conservation in
      patients undergoing RP. The findings suggest that there is no increased risk of
      biochemical failure, disease dissemination, or mortality at 5 years post-RP as a
      result of ICS use.

PMID- 22612660
TI  - Alitretinoin abrogates innate inflammation in palmoplantar pustular psoriasis.
AB  - BACKGROUND: Palmoplantar pustular psoriasis is often recalcitrant to therapy.
      Here we evaluated the therapeutic effect of alitretinoin in patients with
      recalcitrant palmoplantar pustular psoriasis and investigated subsequent
      immunopathological alterations. METHODS: Seven patients with palmoplantar
      pustular psoriasis were treated with oral alitretinoin 30 mg once daily for 12
      weeks. Efficacy was assessed by palmoplantar pustular psoriasis area and severity
      index (PPPASI), visual analogue scales (VAS) on intensity of pain and pruritus
      and an overall patient assessment. Immunohistochemical staining for neutrophil
      elastase, CD3, CD4, CD8, CD1a CD11c, CD303,CD68, CD69, CD208 and HLA-DR was on
      lesional skin biopsies obtained before and after 12 weeks of treatment. RESULTS:
      PPPASI and VAS for pruritus and pain decreased significantly after 12 weeks of
      treatment with alitretinoin. The overall patient assessment ranged from 60% to
      90% clinical improvement. In correlation with clinical improvement a significant
      reduction, particularly of neutrophils, macrophages and dendritic cells, was also
      observed in the skin sections. Alitretinoin was well tolerated except for
      headache during the first month of treatment in two patients. Limitations of the
      study are a missing control group and the concomitant usage of topical therapy.
      DISCUSSION: Our findings suggest that alitretinoin may represent a new and
      promising therapy for recalcitrant palmo-plantar psoriasis and warrants further
      controlled studies to confirm efficacy and safety of alitretinoin in this
      disease.

PMID- 22612663
TI  - AIDS-related Kaposi's sarcoma involving the genital and inguinal regions.

PMID- 22612662
TI  - Adjunctive rectal misoprostol versus oxytocin infusion for prevention of
      postpartum hemorrhage in women at risk: a randomized controlled trial.
AB  - AIM: The aim of this study was to evaluate the efficacy of adjunctive rectal
      misoprostol compared to oxytocin infusion in the prevention of primary postpartum
      hemorrhage after routine active management of the third stage of labor in women
      with identifiable risk factors for uterine atony. MATERIAL AND METHODS: A double
      blind randomized controlled trial was carried out at Obafemi Awolowo University
      Teaching Hospitals Complex, Ile-Ife, Nigeria. A total of 264 parturients with
      known risk factors for postpartum hemorrhage were randomized to receive either
      rectal misoprostol (600 ug; n = 132) or oxytocin infusion (20 IU in 500 mL; n =
      132) after routine active management of the third stage of labor. Intrapartum
      blood loss was measured using a combination of the BRASSS-V calibrated drapes and
      differential pad weighing. Hematocrit was measured intrapartum and 24 h
      postpartum. RESULTS: There was no significant difference (P = 0.07) in the mean
      intrapartum blood loss between the misoprostol (387.28 +/- 203.09 mL) and
      oxytocin (386.73 +/- 298.51 mL) groups. There was also no difference in the
      requirement for additional intervention for uterine atony (P = 0.74). Postpartum
      hematocrit drop and blood transfusion were, however, significantly less in the
      misoprostol group. CONCLUSION:  Rectal misoprostol is as effective as oxytocin
      infusion as an adjunct for prevention of postpartum hemorrhage in women with risk
      factors for uterine atony and is associated with a lower hematocrit drop and
      blood transfusion postpartum. However, shivering, pyrexia and vomiting are more
      frequent with misoprostol, though usually self-limited.

PMID- 22612665
TI  - D-dimer levels in stable COPD patients: a case-control study.
AB  - BACKGROUND: High D-dimer levels have been detected in patients with chronic
      obstructive pulmonary disease (COPD) exacerbation, irrespective of presence of
      venous thromboembolism. On the other hand, there is a continuing debate about the
      diagnostic efficiency of D-dimer tests in patients with stable COPD. OBJECTIVES:
      We aimed to investigate if basic laboratory investigations suggest
      hypercoagulability state in stable COPD patients, and if there is an association
      with D-dimer levels and pulmonary function tests. METHODS: We conducted a case
      control study. COPD patients and controls were matched for sex and age in a 2:1
      matching ratio. D-dimer levels and pulmonary function tests were performed in
      COPD patients and controls. RESULTS: A total of 58 COPD patients and 30 controls
      met the inclusion criteria and were included in the analysis. The median of D
      dimers was 0.24 ng/mL (IQR: 0.21-0.36 ng/mL) in COPD group and 0.17 ng/mL (IQR:
      0.12-0.24 ng/mL) in control group. This difference was not statistically
      significant (p = 0.102). Using bivariate correlations, we found significant
      positive correlations between BMI and D-dimers in COPD patients (r = 0.3, p =
      0.024). CONCLUSIONS: We found that levels of D-dimers in stable COPD were not
      different as compared to control subjects. Our results also suggest that BMI
      could lead to disturbances in coagulation system.

PMID- 22612664
TI  - Lipopolysaccharide O-antigen of enterohemorrhagic Escherichia coli O157:H7 is
      required for killing both insects and mammals.
AB  - Studies of enterohemorrhagic Escherichia coli (EHEC) infection mechanisms using
      mammals require large numbers of animals and are both costly and associated with
      ethical problems. Here, we evaluated the pathogenic mechanisms of EHEC in the
      silkworm model. Injection of a clinically isolated EHEC O157:H7 Sakai into either
      the silkworm hemolymph or intraperitoneal fluid of mice killed the host animals.
      EHEC O157:H7 Sakai deletion mutants of the rfbE gene, which encodes perosamine
      synthetase, a monosaccharide component synthetase of the O-antigen, or deletion
      mutants of the waaL gene, which encodes O-antigen ligase against the lipid A-core
      region of lipopolysaccharide (LPS), had attenuated killing ability in both
      silkworms and mice. Introduction of the rfbE gene or the waaL gene into the
      respective mutants restored the killing ability in silkworms. Growth of both
      mutants was inhibited by a major antimicrobial peptide in the silkworm hemolymph,
      moricin. The viability of both mutants was decreased in swine serum. The
      bactericidal effect of swine serum against both mutants was inactivated by heat
      treatment. These findings suggest that the LPS O-antigen of EHEC O157:H7 plays an
      important defensive role against antimicrobial factors in the host body fluid and
      is thus essential to the lethal effects of EHEC in animals.

PMID- 22612667
TI  - Treating stimuli as a random factor in social psychology: a new and comprehensive
      solution to a pervasive but largely ignored problem.
AB  - Throughout social and cognitive psychology, participants are routinely asked to
      respond in some way to experimental stimuli that are thought to represent
      categories of theoretical interest. For instance, in measures of implicit
      attitudes, participants are primed with pictures of specific African American and
      White stimulus persons sampled in some way from possible stimuli that might have
      been used. Yet seldom is the sampling of stimuli taken into account in the
      analysis of the resulting data, in spite of numerous warnings about the perils of
      ignoring stimulus variation (Clark, 1973; Kenny, 1985; Wells & Windschitl, 1999).
      Part of this failure to attend to stimulus variation is due to the demands
      imposed by traditional analysis of variance procedures for the analysis of data
      when both participants and stimuli are treated as random factors. In this
      article, we present a comprehensive solution using mixed models for the analysis
      of data with crossed random factors (e.g., participants and stimuli). We show the
      substantial biases inherent in analyses that ignore one or the other of the
      random factors, and we illustrate the substantial advantages of the mixed models
      approach with both hypothetical and actual, well-known data sets in social
      psychology (Bem, 2011; Blair, Chapleau, & Judd, 2005; Correll, Park, Judd, &
      Wittenbrink, 2002).

PMID- 22612666
TI  - Fluorescence excitation and imaging of single molecules near dielectric-coated
      and bare surfaces: a theoretical study.
AB  - Microscopic fluorescent samples of interest to cell and molecular biology are
      commonly embedded in an aqueous medium near a solid surface that is coated with a
      thin film such as a lipid multilayer, collagen, acrylamide, or a cell wall. Both
      excitation and emission of fluorescent single molecules near film-coated surfaces
      are strongly affected by the proximity of the coated surface, the film thickness,
      its refractive index and the fluorophore's orientation. For total internal
      reflection excitation, multiple reflections in the film can lead to resonance
      peaks in the evanescent intensity versus incidence angle curve. For emission,
      multiple reflections arising from the fluorophore's near field emission can
      create a distinct intensity pattern in both the back focal plane and the image
      plane of a high aperture objective. This theoretical analysis discusses how these
      features can be used to report film thickness and refractive index, and
      fluorophore axial position and orientation.

PMID- 22612668
TI  - Failure to deliver therapy by a Riata Lead with internal wire externalization and
      normal electrical parameters during routine interrogation.
AB  - We present a case of failure to deliver a shock by a St. Jude Medical
      defibrillator involving a Riata lead that was discovered incidentally while the
      device was attempting to deliver inappropriate therapy. Routine interrogation,
      including high voltage (HV) impedance, failed to reveal any abnormality. Failure
      to deliver therapy was confirmed during DFT testing, which revealed extremely low
      HV impedance only while attempting to deliver therapy. Fluoroscopy indicated
      moderate externalization of internal wires. This case highlights an under
      recognized issue with St. Jude Medical systems, namely the possibility that
      therapy may not be delivered despite the presence of normal electrical parameters
      during routine surveillance.

PMID- 22612669
TI  - Efficacy of reduction therapy of natural human beta-interferon and ribavirin in
      elderly patients with chronic hepatitis C, genotype 1b and high viral load.
AB  - AIM:   To evaluate the efficacy of reduction therapy of natural human interferon
      (IFN)-beta and ribavirin in elderly patients with hepatitis C virus (HCV)
      genotype 1b and high viral load who had complications of anemia, low bodyweight
      (<50 kg), diabetes mellitus and/or hypertension. METHODS:   Inclusion criteria
      were age of 65 years or older, HCV genotype 1b, and serum HCV RNA level of 5.0
      logIU/mL or higher. A total of 23 subjects with hemoglobin level of less than 13
      g/dL, low bodyweight, diabetes mellitus and/or hypertension were enrolled in this
      study (reduction-dose group). IFN-beta was administrated i.v. at a dose of 6
      million units daily for 4 weeks initially, followed by three times a week for 44
      weeks. Ribavirin was given daily for 48 weeks at a decreased dose of one tablet
      per day compared to the ordinary dose described based on bodyweight. As a
      control, another 22 patients without anemia, low bodyweight and/or complications
      treated with the standard dose of ribavirin (standard-dose group) were enrolled.
      RESULTS:   Patients' rates with further dose reduction or discontinuation of
      treatment was 26.1% (6/23) in the reduction-dose group and 77.3% (17/22) in the
      standard-dose group. The sustained virological response (SVR) was 39.1% (9/23) in
      the reduction-dose group and 27.3% (6/22) in the standard-dose group (P = 0.404).
      Based on genetic variations near the IL28B gene (rs8099917), SVR was 44.1%
      (15/34) in patients with TT and 0% (0/11) in patients with TG (P = 0.008).
      CONCLUSION:   The reduction therapy of IFN-beta and ribavirin in elderly HCV
      patients with genotype 1b, high viral load, IL28B gene (rs8099917) of TT who had
      complications of anemia, low bodyweight, diabetes mellitus and/or hypertension is
      one possible selection of treatment.

PMID- 22612670
TI  - Familial pituitary adenomas - who should be tested for AIP mutations?
AB  - Familial Isolated Pituitary Adenomas (FIPA), an autosomal dominant disease with
      low penetrance is being increasingly recognized. FIPA families can be divided
      into two distinct groups based on genetic and phenotypic features. Patients with
      mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are
      characterized by young-onset somatotroph or lactotroph macroadenomas, while in
      the other, larger group of FIPA patients with typically adult-onset disease and
      more varied adenoma types, no causative gene(s) has been identified. Young-onset
      macroadenoma patients can also be identified with germline AIP mutation without
      an apparent family history. Further data and longer follow-up are necessary to
      establish formal guidelines, but the current data suggest genetic screening of
      the AIP gene in patients with a pituitary adenoma and no other associated
      features who have (i) a family history of pituitary adenoma, (ii) childhood-onset
      pituitary adenoma or (iii) a pituitary somatotroph or lactotroph macroadenoma
      diagnosed before the age of 30 years.

PMID- 22612671
TI  - Alcohol consumption is associated with reduced risk of Type 2 diabetes and
      autoimmune diabetes in adults: results from the Nord-Trondelag health study.
AB  - AIMS: We investigated the influence of different aspects of alcohol consumption
      on the risk of Type 2 diabetes and autoimmune diabetes in adults. METHODS: We
      used data from the Nord-Trondelag Health Survey (HUNT) study, in which all adults
      aged >= 20 years from Nord-Trondelag County were invited to participate in three
      surveys in 1984-1986, 1995-1997 and 2006-2008. Patients with diabetes were
      identified using self-reports, and participants with onset age >= 35 years were
      classified as having Type 2 diabetes if they were negative for anti-glutamic acid
      decarboxylase (n = 1841) and as having autoimmune diabetes if they were positive
      for anti-glutamic acid decarboxylase (n = 140). Hazard ratios of amount and
      frequency of alcohol use, alcoholic beverage choice, and binge drinking and
      alcohol use disorders were estimated. RESULTS: Moderate alcohol consumption
      (adjusted for confounders) was associated with a reduced risk of Type 2 diabetes
      in men, but not in women (hazard ratio for men 10-15 g/day 0.48, 95% CI 0.28
      0.77; hazard ratio for women >= 10 g/day 0.81, 95% CI 0.33-1.96). The reduced
      risk was primarily linked to consumption of wine [hazard ratio 0.93, 95% CI 0.87
      0.99 (per g/day)]. No increased risk was seen in participants reporting binge
      drinking or in problem drinkers. The results were also compatible with a reduced
      risk of autoimmune diabetes associated with alcohol consumption [hazard ratio
      0.70, 95% CI 0.45-1.08 (frequent consumption) and hazard ratio 0.36, 95% CI 0.13
      0.97 (2-7 g/day)]. CONCLUSIONS: Moderate alcohol consumption associates with
      reduced risk of both Type 2 diabetes and autoimmune diabetes. A protective effect
      of alcohol intake may be limited to men. High alcohol consumption does not seem
      to carry an increased risk of diabetes.

PMID- 22612672
TI  - Evaluating the rate of recurrence of epilepsy after therapy discontinuation in 2
      year seizure-free epileptic patients.
AB  - INTRODUCTION: The potential complications of antiepileptic drugs render them
      risky and associated with numerous morbidities for long-term therapy. Therefore,
      it is essential to balance therapy discontinuation against risks of epilepsy
      recurrence. However, the risk factors predicting recurrence are yet to be
      identified. The present study was conducted in order to determine the rate of
      recurrence after gradual therapy discontinuation as well as its influential
      factors in epileptic patients under medical therapy who were seizure-free for a
      period of 2 years. METHOD AND MATERIALS: This is a descriptive cross-sectional
      study on epileptic patients who referred to the specialized neurology clinic of
      Kermanshah University of Medical Sciences from 1994 to 2010. The data were
      extracted from patients' medical records and analyzed. FINDINGS: A total of 391
      patients were evaluated. In our study, 51.2% of patients experienced recurrence
      of seizure at the end of the 2-year follow-up. Recurrence occurred most
      frequently during medication tapering (51%). While the largest number of patients
      were aged under 12 years (178 patients; 45%), the rate of recurrence was greatest
      for patients aged 20-40 years (43 patients; 66.2%). DISCUSSION AND CONCLUSION: As
      our findings suggest, type of epilepsy, multidrug therapy, abnormal
      electroencephalography before discontinuation, and abnormal brain computed
      tomography scan are factors that influence the risk of recurrence after therapy
      discontinuation. It is essential for the physician to take these factors into
      account and weigh the risk of recurrence against the benefits of therapy
      discontinuation.

PMID- 22612674
TI  - Retrospective evaluation of presenting temperature of urethral obstructed male
      cats and the association with severity of azotemia and length of hospitalization:
      243 cats (2006-2009).
AB  - OBJECTIVES: To evaluate whether the presenting rectal temperature and level of
      azotemia predicts the length of hospitalization (LOH) in a population of
      obstructed male cats. To describe the relationships between physical examination
      parameters, blood electrolytes, and azotemia in a clinical population of
      obstructed male cats. DESIGN: Retrospective clinical study. SETTING: Emergency
      and referral specialty hospitals. ANIMALS: Two hundred and forty-three male cats
      that presented with urethral obstruction between 2006 and 2009. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: No significant association between the hours
      of hospitalization and rectal temperature was detected (P = 0.39). Blood urea
      nitrogen (BUN) and creatinine (CREA) concentrations were positively correlated
      with LOH (P < 0.01). BUN and CREA were significantly higher (P < 0.01) for the
      hypothermic group compared to the normothermic group. Potassium was negatively
      correlated to heart rate and rectal temperature but positively correlated to BUN
      and CREA. CONCLUSION: No association with regard to rectal temperature and LOH
      could be demonstrated in this population of cats. However, the presence of
      azotemia in obstructed male cats appears to provide the clinician with additional
      information regarding the necessary LOH and eventual cost to the client.

PMID- 22612673
TI  - Design of the Wearable Power-Assist Locomotor (WPAL) for paraplegic gait
      reconstruction.
AB  - PURPOSE: To develop and clinically evaluate a novel assistive walking system, the
      Wearable Power-Assist Locomotor (WPAL). METHODS: To evaluate the performance of
      WPAL, a clinical trial is conducted with four paraplegic patients. After fitting
      the WPAL, patients learned to use the WPAL. The length and duration of
      independent walking was measured and compared to conventional orthosis
      (Primewalk). RESULTS: After training, all patients were able to stand, sit, and
      walk independently with the WPAL. Compared to a conventional orthosis
      (Primewalk), the duration and distance of independent ambulation increased. The
      physiological cost index (PCI), perceived exertion and EMG of upper extremities
      decreased. CONCLUSIONS: WPAL might greatly enhance the possibility of restoration
      gait to paraplegic patients.

PMID- 22612675
TI  - Discovery bioanalysis. Foreward.

PMID- 22612676
TI  - Surrendering to the robot army: why we resist automation in drug discovery and
      development.

PMID- 22612677
TI  - Building up a sweat for easier clinical testing.

PMID- 22612678
TI  - Conference report: Isranalytica 2012.
AB  - The Isranalytica, organized by the Israel Analytical Chemical Society, is the
      largest analytical conference in Israel and has become one of the largest annual
      conferences in analytical chemistry in the world. Over the past years,
      Isranalytica has achieved major success and become the most prestigious
      analytical chemistry meeting in Israel.

PMID- 22612679
TI  - Bioanalysis young investigator: Pan Deng.
AB  - I would like to nominate Pan Deng for the Bioanalysis Young Investigator Award
      2012. Her research projects include developing LC-MS/MS methods for the
      quantification of small and large molecules to support drug pharmacokinetic
      studies. During her PhD training in my laboratory, she has gained much experience
      in developing sensitive LC-MS/MS methods for the measurement of various
      compounds, especially polar analytes, and published several research and review
      papers. As part of her PhD project, she also investigated the metabolism of drugs
      utilizing UPLC-Q/TOF MS. Her efforts in studying drug metabolism study have led
      to the finding of new metabolites, and unveiling the metabolic pathways of
      several new drug candidates. She is currently expanding her research into the
      area of drug toxicity. Hopefully this Young Investigator Award will encourage
      Deng to have greater achievements.

PMID- 22612680
TI  - Bioanalysis young investigator: Sathyadevi Venkataramani.
AB  - It is with great pleasure that I am writing to recommend Sathyadevi Venkataramani
      who works as a Scientist in Integrated BioTherapeutics (IBT). Sathya did her
      graduate research work at the University of Zurich (Switzerland) where she
      focused on using various bioanalytical tools to characterize the stability of
      repeat proteins that are emerging as excellent alternatives to antibody therapy.
      She successfully published her research findings in journals including Protein
      Science, Biochemistry and Current Microbiology. As a postdoctoral associate at
      Stanford University (CA, USA) and as a Scientist in Solus Biosystems (CA, USA),
      she thoroughly investigated the applications of spectroscopy and chromatography
      for characterizing the stability of monoclonal antibodies and other therapeutic
      proteins. Being the first author in all her publications and corresponding author
      of her last few highlights her highly competent skills (both writing and oral),
      enthusiasm, research motivation, hard work, scientific capabilities, innovative
      thinking and the terrific passion in implementing those. I am very impressed that
      she is serving as an ad-hoc peer reviewer for journals such as Molecular Biology
      Reports, American Association of Pharmaceutical Scientists PharmSciTech, Research
      and Reports in Biochemistry and as a Faculty of Biochemistry for Webmed Central.
      Currently she is leading the protein chemistry group in Integrated
      BioTherapeutics, Inc. (IBT) and is already in possession of a couple of
      manuscripts and patents from IBT. Her expertise and unquenchable enthusiasm in
      the bioanalysis field have tremendously helped to improve the quality and
      quantity of proteins in IBT. It is a very commendable idea of Bioanalysis to
      appreciate and recognize the young rising stars of the scientific world and I am
      very excited and honored to recommend Sathya among those for the year 2012.

PMID- 22612681
TI  - Discovery biotherapeutics bioanalysis: challenges and possible solutions.

PMID- 22612682
TI  - Simultaneous qualitative and quantitative metabolism data generation: a
      convenient marriage?

PMID- 22612683
TI  - High-throughput quantitation of large molecules using multiplexed chromatography
      and high-resolution/accurate mass LC-MS.
AB  - BACKGROUND: High-throughput screening with LC-MS has been routinely implemented
      to various degrees throughout the entire drug-discovery process. One of the major
      advantages of utilizing LC-MS earlier at the lead discovery stage is reducing the
      cost of sample analysis while increasing assay selectivity. Avoiding labeling
      agents and other non-native species in an assay environment can reduce costly
      sample preparation, while chromatographic separation of the analyte of interest
      from interferences in the sample matrix has been shown to increase selectivity
      and sensitivity. METHOD: In this paper, we utilize high-resolution MS-LC
      multiplexing to analyze phosphorylated peptides as part of a screening assay.
      Commonly used enzyme buffers were used to prepare phosphorylated peptide
      standards of varying concentrations and these were plated into a 96-well plate
      format for LC-MS analysis. The overall cycle time for analysis from sample to
      sample, LLOQ, Z' and coefficient of variance were determined. CONCLUSION: High
      resolution MS coupled with LC multiplexing provides high-quality sample analysis
      at sampling rates of up to 18 s per sample. Samples analyzed in both simple and
      complex sample matrixes demonstrated an LOQ of 5 nM with linear response across
      the working range of the assay. Overall statistical analysis of the large samples
      produced Z' = 0.85 for sample sets in sodium citrate solution and Z' = 0.66 for
      sample sets in HEPES solution indicating a robust analytical method.

PMID- 22612684
TI  - Universal LC-MS method for minimized carryover in a discovery bioanalytical
      setting.
AB  - BACKGROUND: A frequent impediment to accurate quantitation in bioanalytical LC-MS
      arises from carryover. For many new chemical entities in drug discovery carryover
      is not limited to the autosampler, but instead arises from several different
      sources. METHOD: We tested several different columns, injector wash sequences and
      gradient compositions to understand and eliminate these sources. In many
      instances carryover was dictated by the elution gradient and column as much as
      the autosampler hardware and wash protocol. CONCLUSION: Several trends were
      observed. First, different columns resulted in significantly different amounts of
      carryover (even for nominally the same column chemistry). Second, a continuous
      high organic wash of the column was not as effective at removing carryover as
      cycling between high and low organic mobile phases during the column wash.
      Combining our observations (column, gradient and autosampler configuration) we
      devised a short 3-min method that is appropriate for a diverse set of new
      chemical entities and minimizes carryover while still being sufficiently robust
      to use in a drug-discovery setting.

PMID- 22612685
TI  - Development of a high-speed, multiplexed sample-delivery instrument for LC-MS/MS
      bioanalysis.
AB  - BACKGROUND: The number of new chemical entities and types of in vitro and in vivo
      samples that require bioanalysis in drug discovery is large and diverse. In
      addition, method development time is limited as data turnaround is the highest
      priority. These circumstances require that a well-defined set of bioanalysis
      options be available in short timeframes to triage samples for analysis. METHOD:
      The Apricot Designs Dual Arm (ADDA) instrument is an LC-MS/MS sample delivery
      system that features a flexible hardware design coupled with software automation
      to enhance throughput in LC-MS/MS bioanalysis drug discovery. The instrument can
      perform high-throughput LC-MS/MS (8-10 s/sample) for screening and in vitro
      bioanalysis, as well as multiplexed LC for traditional gradient or isocratic LC
      approaches. The instrument control software is designed to integrate with
      DiscoveryQuantTM software (AB Sciex) and a global database of MS/MS conditions.
      CONCLUSION: Development of the sample delivery platform and its application in
      high-throughput and gradient LC will be described.

PMID- 22612686
TI  - A bioanalytical strategy utilizing dried blood spot sampling and LC-MS/MS in
      discovery toxicology studies.
AB  - BACKGROUND & METHOD: The small sample volumes characteristic to dried blood spot
      (DBS) sampling enabled us to right-shift the linear dynamic range of an LC-MS/MS
      plasma assay tenfold and eliminate the need for extensive sample dilution in
      support of three discovery toxicology studies in which both plasma and DBS
      samples were collected. With the right-shifted DBS assay range, no DBS study
      samples required dilution, while all of the plasma samples were diluted 5-50
      fold. RESULTS: DBS standard curves from 78-80,000 nM were linear, the performance
      of the curve and QC samples was within acceptable discovery-assay criteria and
      individual plasma and DBS data were comparable. Linear correlations of C(max) and
      AUC derived from DBS and plasma data resulted in R(2) > 0.9. CONCLUSION: This
      bioanalytical strategy represents a benefit to the bioanalyst that can expedite
      the return of data and minimize the potential for error and variability that can
      result from extensive dilutions of study samples.

PMID- 22612687
TI  - A simplified approach for the simultaneous qualification of bioanalytical methods
      for multiple species at late discovery stage.
AB  - BACKGROUND: Although not required to be GLP compliant, the bioanalytical methods
      intended to be used in supporting pharmacokinetic and exploratory toxicokinetic
      characterization of compounds in late drug-discovery stage are highly desirable
      to be qualified with respect to accuracy, precision, matrix effects and
      selectivity, as well as various stability assessments. Since the method
      qualification for each species is typically conducted separately, it is often
      resource-intensive and time-consuming. RESULTS: In this work, we report a
      simplified approach to perform a non-GLP, multiple-species, bioanalytical-method
      qualification. In this approach, QC samples prepared from multiple species were
      quantified against standard curves from a single species. More importantly,
      multiple stability assessments were combined to produce combination stability QC
      samples under the assumption that if the combination stability QC samples met the
      acceptance criteria, so did each individual stability assessment. CONCLUSION:
      Using this simplified approach, a method qualification was typically completed in
      less than 2 weeks compared with the 5-8 weeks of a conventional method
      qualification. This approach was found to be useful for bioanalytical methods
      developed for both plasma and whole blood matrices.

PMID- 22612688
TI  - Discovery pharmacokinetic studies in mice using serial microsampling, dried blood
      spots and microbore LC-MS/MS.
AB  - BACKGROUND: Initial pharmacokinetic (PK) studies of discovery compounds are
      conducted in mice to demonstrate exposure prior to conducting efficacy studies.
      PK information obtained from a single mouse by serial blood microsampling, dried
      blood spot collection and analyses using microbore (1 mm internal diameter
      column) LC-MS/MS is presented. Ex vivo blood to plasma concentration ratios
      (BPRs) from mouse PK studies were compared with in vitro BPRs for 15 compounds.
      RESULTS: Two compounds were orally dosed and blood was collected at time points
      via serial blood sampling. The calculated PK parameters (AUC, T(max) and C(max))
      were comparable across liquid blood, dried blood spot and plasma matrices. The
      BPR results from both methods were comparable. CONCLUSION: Serial blood
      microsampling has led to reduced animal and compound usage with improved PK data.
      Ex vivo BPR is suitable in a discovery setting. Microbore LC-MS/MS is well suited
      in instances where sample volume is limited, and enables faster analyses, reduced
      solvent use, and less frequent MS source cleaning.

PMID- 22612689
TI  - Recent development in software and automation tools for high-throughput discovery
      bioanalysis.
AB  - Bioanalysis with LC-MS/MS has been established as the method of choice for
      quantitative determination of drug candidates in biological matrices in drug
      discovery and development. The LC-MS/MS bioanalytical support for drug discovery,
      especially for early discovery, often requires high-throughput (HT) analysis of
      large numbers of samples (hundreds to thousands per day) generated from many
      structurally diverse compounds (tens to hundreds per day) with a very quick
      turnaround time, in order to provide important activity and liability data to
      move discovery projects forward. Another important consideration for discovery
      bioanalysis is its fit-for-purpose quality requirement depending on the
      particular experiments being conducted at this stage, and it is usually not as
      stringent as those required in bioanalysis supporting drug development. These
      aforementioned attributes of HT discovery bioanalysis made it an ideal candidate
      for using software and automation tools to eliminate manual steps, remove
      bottlenecks, improve efficiency and reduce turnaround time while maintaining
      adequate quality. In this article we will review various recent developments that
      facilitate automation of individual bioanalytical procedures, such as sample
      preparation, MS/MS method development, sample analysis and data review, as well
      as fully integrated software tools that manage the entire bioanalytical workflow
      in HT discovery bioanalysis. In addition, software tools supporting the emerging
      high-resolution accurate MS bioanalytical approach are also discussed.

PMID- 22612690
TI  - SPE-MS analysis of absorption, distribution, metabolism and excretion assays: a
      tool to increase throughput and steamline workflow.
AB  - In an effort to create faster and more efficient bioanalytical methods for drug
      development, many investigators have evaluated a variety of SPE-MS systems. Over
      the past 15 years online systems have evolved from run times of >1.5 min/sample
      to <10 s/sample. High-throughput SPE-MS methods for in vitro absorption,
      distribution, metabolism and excretion screening assays have been described by
      several laboratories and shown to produce results comparable to conventional LC
      MS/MS systems. While quantitative analysis of small molecules in biological
      matrixes holds many challenges, for several applications SPE-MS methods have
      achieved comparable results to LC-MS/MS with the benefit of 10-30-times the
      throughput. Based on its distinct advantages of throughput and streamlined
      workflow efficiencies, SPE-MS is a useful tool for the analysis of many in vitro
      absorption, distribution, metabolism and excretion assays and in vivo
      bioanalytical studies. Further development of SPE-MS methods and analysis
      workflows has the potential to expand the capabilities of this technology for
      other challenging bioanalytical applications.

PMID- 22612691
TI  - Recent advances in bioanalytical sample preparation for LC-MS analysis.
AB  - Sample preparation has historically been, and continues to be, the most
      challenging part of the bioanalytical workflow. Several techniques have been
      developed over the years to deal with the problems of recovery and matrix effects
      in an effort to increase the reliability and robustness of the bioanalytical
      method. In recent years certain techniques have come into prominence and gained
      acceptance in routine sample preparation, and some have shown promise in their
      use in a discovery environment where speed is critical and method development
      time is often limited. The aim of this review is to examine several of these
      techniques and provide examples of their use from the literature, as well as
      comment on their utility in current workflows.

PMID- 22612692
TI  - Emerging medication for the treatment of male hypogonadism.
AB  - INTRODUCTION: Since the phenotype and clinical need of the hypogonadal
      individuals changes dramatically over time, versatile therapies are needed. AREAS
      COVERED: The authors review the available evidence on possible therapies. EXPERT
      OPINION: In the case of primary hypogonadism starting early in life, substitution
      with testosterone (T) is the only choice. For secondary congenital hypogonadism,
      we recommend starting with gonadotrophins to allow the testes to reach pubertal
      size. Thereafter, T replacement therapy can be administered until fertility is
      desired. At that time, gonadotrophins should be employed until fathering occurs.
      Antiestrogens are an alternative, however, their efficacy has not been adequately
      tested. In the presence of increased estrogen production symptoms (breast
      tenderness and gynecomastia), a short-term trial with non-aromatizable androgens
      (dihydrotestosterone mesterolone or oxandrolone) could be advisable. However,
      after a few months of therapy, switching to other aromatizable preparations is
      recommended, to prevent bone loss. When prostate safety is concerned, the use of
      steroidal or non-steroidal selective androgen receptor modulators that are less
      susceptible to 5alpha reduction might be advisable. An attractive possibility is
      the combined use of testosterone with 5alpha inhibitors. Theoretically, also
      estrogen receptor-beta ligands could be employed, however the development of
      these compounds, although promising, is still in its infancy.

PMID- 22612694
TI  - Efficient light trapping in inverted nanopyramid thin crystalline silicon
      membranes for solar cell applications.
AB  - Thin-film crystalline silicon (c-Si) solar cells with light-trapping structures
      can enhance light absorption within the semiconductor absorber layer and reduce
      material usage. Here we demonstrate that an inverted nanopyramid light-trapping
      scheme for c-Si thin films, fabricated at wafer scale via a low-cost wet etching
      process, significantly enhances absorption within the c-Si layer. A broadband
      enhancement in absorptance that approaches the Yablonovitch limit (Yablonovitch,
      E. J. Opt. Soc. Am.1987, 72, 899-907 ) is achieved with minimal angle dependence.
      We also show that c-Si films less than 10 MUm in thickness can achieve
      absorptance values comparable to that of planar c-Si wafers thicker than 300 MUm,
      amounting to an over 30-fold reduction in material usage. Furthermore the surface
      area increases by a factor of only 1.7, which limits surface recombination losses
      in comparison with other nanostructured light-trapping schemes. These structures
      will not only significantly curtail both the material and processing cost of
      solar cells but also allow the high efficiency required to enable viable c-Si
      thin-film solar cells in the future.

PMID- 22612693
TI  - Influences of mutations on the electrostatic binding free energies of chloride
      ions in Escherichia coli ClC.
AB  - Mutations in ClC channel proteins may cause serious functional changes and even
      diseases. The function of ClC proteins mainly manifests as Cl(-) transport, which
      is related to the binding free energies of chloride ions. Therefore, the
      influence of a mutation on ClC function can be studied by investigating the
      mutational effect on the binding free energies of chloride ions. The present
      study provides quantitative and systematic investigations on the influences of
      residue mutations on the electrostatic binding free energies in Escherichia coli
      ClC (EcClC) proteins, using all-atom molecular dynamics simulations. It was found
      that the change of the electrostatic binding free energy decreases linearly with
      the increase of the residue-chloride ion distance for a mutation. This work
      reveals how changes in the charge of a mutated residue and in the distance
      between the mutated residue and the binding site govern the variations in the
      electrostatic binding free energies and therefore influence the transport of
      chloride ions and conduction in EcClC. This work would facilitate our
      understanding of the mutational effects on transport of chloride ions and
      functions of ClC proteins and provide a guideline to estimate which residue
      mutations will have great influences on ClC functions.

PMID- 22612695
TI  - Adherence to treatment with selective serotonin reuptake inhibitors and the risk
      for fractures and bone loss: a population-based cohort study.
AB  - BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are suspected of
      increasing the risk of bone loss and osteoporotic fractures. OBJECTIVE: The aim
      of this study was to investigate the association between adherence to SSRI
      treatment and the risk of bone loss-related events. METHODS: The data used in
      this retrospective cohort study are part of the ongoing medical documentation
      routinely collected in a large health maintenance organization in Israel.
      Specifically, we used the information collected between January 2004 and April
      2010. The study cohort included 10 621 women who were new users of SSRIs. Bone
      loss-related events were defined as fractures or initiation of bisphosphonate
      treatment. Adherence level was assessed by calculating the proportion of days
      covered (PDC) with an SSRI from the date of first dispensed SSRI (index date) to
      the end of follow-up and was categorized as low (PDC <=20%), intermediate (PDC 21
      79%) and high (PDC >=80%). To validate the study model, we conducted a similar
      analysis on patients using antiepileptic drugs, which are known to be positively
      associated with an increased risk of osteoporotic fractures. RESULTS: Higher
      adherence to SSRI treatment was significantly associated with an increased risk
      of bone loss-related events in a dose-response manner. The adjusted hazard ratio
      for bone loss-related events adjusted for age, physician visits and body mass
      index in patients who were covered with an SSRI for 21-79% of the time and 80% or
      more of the time was 1.15 (95% CI 0.97, 1.37) and 1.40 (95% CI 1.14, 1.73)
      compared with patients who were covered for less than 21% of the follow-up
      period. CONCLUSION: Exposure to SSRI treatment is associated with an increased
      risk of bone loss-related events. Further studies are required to determine the
      causality of the association and its relevance to the clinical use of SSRIs.

PMID- 22612696
TI  - Drug-loaded nanocarriers: passive targeting and crossing of biological barriers.
AB  - Poor bioavailability and poor pharmacokinetic characteristics are some of the
      leading causes of drug development failure. Therefore, poorly-soluble drugs,
      fragile proteins or nucleic acid products may benefit from their encapsulation in
      nanosized vehicles, providing enhanced solubilization, protection against
      degradation, and increased access to pathological compartments. A key element for
      the success of drug-loaded nanocarriers is their ability to either cross
      biological barriers themselves, or allow loaded drugs to traverse them to achieve
      optimal pharmacological action at pathological sites. Depending on the mode of
      administration, nanocarriers may have to cross different physiological barriers
      in their journey towards their target. In this review, the crossing of biological
      barriers by passive targeting strategies will be presented for intravenous
      delivery (vascular endothelial lining, particularly for tumor vasculature and
      blood brain barrier targeting), oral administration (gastrointestinal lining),
      and upper airway administration (pulmonary epithelium). For each specific
      barrier, background information will be provided on the structure and biology of
      the tissues involved as well as available pathways for nano-objects or loaded
      drugs (diffusion and convection through fenestration, transcytosis, tight
      junction crossing, etc.). The determinants of passive targeting - size, shape,
      surface chemistry, surface patterning of nanovectors - will be discussed in light
      of current results. Perspectives on each mode of administration will be
      presented. The focus will be on polymeric nanoparticles and dendrimers, although
      advances in liposome technology will be also reported as they represent the
      largest body in the drug delivery literature.

PMID- 22612698
TI  - Antibody-conjugated nanoparticles for therapeutic applications.
AB  - A great challenge to clinical development is the delivery of chemotherapeutic
      agents, known to cause severe toxic effects, directly to diseased sites which
      increase the therapeutic index whilst minimizing off-target side effects.
      Antibody-conjugated nanoparticles offer great opportunities to overcome these
      limitations in therapeutics. They combine the advantages given by the
      nanoparticles with the ability to bind to their target with high affinity and
      improve cell penetration given by the antibodies. This specialized vehicle, that
      can encapsulate several chemotherapeutic agents, can be engineered to possess the
      desirable properties, allowing overcoming the successive physiological conditions
      and to cross biological barriers and reach a specific tissue or cell. Moreover,
      antibody-conjugated nanoparticles have shown the ability to be internalized
      through receptor-mediated endocytosis and accumulate in cells without being
      recognized by the P-glycoprotein, one of the main mediators of multi-drug
      resistance, resulting in an increase in the intracellular concentration of drugs.
      Also, progress in antibody engineering has allowed the manipulation of the basic
      antibody structure for raising and tailoring specificity and functionality. This
      review explores recent developments on active drug targeting by nanoparticles
      functionalized with monoclonal antibodies (polymeric micelles, liposomes and
      polymeric nanoparticles) and summarizes the opportunities of these targeting
      strategies in the therapy of serious diseases (cancer, inflammatory diseases,
      infectious diseases, and thrombosis).

PMID- 22612699
TI  - Integrin-mediated drug delivery in cancer and cardiovascular diseases with
      peptide-functionalized nanoparticles.
AB  - In recent years progress has been speeding in studies of cell-cell interaction
      governed by adhesion molecules, and in particular by integrins and their ligands
      in cells and in the extracellular matrix. Integrins are distributed in a variety
      of tissues and blood cells. An increased expression of integrins and of their
      adhesion counterparts is often observed in sites relevant to disease states.
      Important roles are played by integrin alpha(v)beta(3) in cancer angiogenesis and
      metastatic diffusion, in angiogenesis in ischemic tissues, in atherosclerotic
      damage and restenosis, and in osteoporosis; by integrin alpha(5)beta(1) in
      angiogenesis processes; by integrin alpha(II)bbeta(3), mediating adhesion of
      platelets to fibrinogen, in thrombotic conditions; by integrins alpha(4)beta(1)
      and alpha(L)beta(2) in inflammatory conditions, particularly autoimmune diseases
      and asthma. Therefore, medicinal chemists became attracted and engaged in
      research on integrins as therapeutic and diagnostic targets. Many efforts have
      been directed towards the development of molecular constructs including integrin
      ligands that can provide advanced tools for drug delivery, for imaging, or for
      their combination (theranostics), particularly by exploiting the new
      possibilities offered by nanoparticles. Here we will review the current status
      and the future perspective of integrin targeting of several kind of
      nanoparticles, going from most studied micelles, liposomes, polymeric
      nanoparticles to finish with inorganic nanoparticles of more recent employment.
      Perfluoroalkane filled microbubbles, although over the nanometric size (1-10 MUm)
      will be shortly considered.

PMID- 22612697
TI  - Image-guided nanosystems for targeted delivery in cancer therapy.
AB  - Current challenges in early detection, limitations of conventional treatment
      options, and the constant evolution of cancer cells with metastatic and multi
      drug resistant phenotypes require novel strategies to effectively combat this
      deadly disease. Nanomedical technologies are evolving at a rapid pace and are
      poised to play a vital role in diagnostic and therapeutic interventions - the so
      called "theranostics" - with potential to advance personalized medicine. In this
      regard, nanoparticulate delivery systems can be designed with tumor seeking
      characteristics by utilizing the inherent abnormalities and leaky vasculature of
      solid tumors or custom engineered with targeting ligands for more specific tumor
      drug targeting. In this review we discuss some of the recent advances made in the
      development of multifunctional polymeric nanosystems with an emphasis on image
      guided drug and gene delivery. Multifunctional nanosystems incorporate variety of
      payloads (anticancer drugs and genes), imaging agents (optical probes, radio
      ligands, and contrast agents), and targeting ligands (antibodies and peptides)
      for multi-pronged cancer intervention with potential to report therapeutic
      outcomes. Through advances in combinatorial polymer synthesis and high-throughput
      testing methods, rapid progress in novel optical/radiolabeling strategies, and
      the technological breakthroughs in instrumentation, such as hybrid molecular and
      functional imaging systems, there is tremendous future potential in clinical
      utility of theranostic nanosystems.

PMID- 22612700
TI  - Active drug targeting of disease by nanoparticles functionalized with ligand to
      folate receptor.
AB  - Drug-loaded nanoparticles have shown great potential in the study of carriers for
      disease-targeting drug delivery. Drug-loaded nanoparticles are excellent in
      keeping the drug in the systemic circulation for a prolonged period of time,
      introducing targeting molecules to improve targeting efficiency and to reduce
      side effects. A general review on active drug targeting of cancerous diseases by
      nanoparticles functionalized with ligands to folate receptors is presented
      including the (1) materials and methods for nanoparticle preparation, (2) methods
      for drug encapsulation, (3) surface functionalization of the nanoparticle with
      ligand to folate receptors, and (4) in vitro and in vivo experiments.

PMID- 22612701
TI  - Exploiting the properties of biomolecules for brain targeting of nanoparticulate
      systems.
AB  - The main obstacle in the treatment of central nervous system diseases is
      represented by a limited passage of diagnostic and therapeutic agents across the
      blood-brain barrier, which separates the blood stream from the cerebral
      parenchyma and maintains the homeostasis of the brain. The growing knowledge
      about the brain capillary endothelium and the discovery of specific mechanisms
      for the uptake of substances enables the development of various strategies to
      enhance the drug delivery rate into the brain. Among the different strategies,
      nanoparticles are promising candidates for drug delivery to the brain due to
      their potential in encapsulating drugs and thereby disguising their permeation
      limiting characteristics. Furthermore a surface functionalization of many
      nanoparticles can easily be achieved allowing the active targeting of
      nanoparticles to the brain. For this non-invasive approach, the surface
      functionalization of nanoparticles with biomolecules has shown promising
      potential for effective drug delivery to the brain. This review indexes the main
      classes of biomolecules used for the surface functionalization of nanoparticles
      and discusses their potential as drug delivery systems for an enhanced passage of
      diagnostic and therapeutic agents into the brain parenchyma.

PMID- 22612702
TI  - Drug targeting to cancer by nanoparticles surface functionalized with special
      biomolecules.
AB  - Nanoparticulate-based drug carriers have been developed to overcome the problems
      of conventional anticancer pharmacotherapy, i.e., the little specificity and low
      accumulation of the drug into the tumor interstitium, and the extensive
      biodistribution leading to severe toxicity. Unfortunately, conventional
      nanoparticles have been demonstrated to merely accumulate the loaded drug into
      organs associated to the reticuloendothelial system, e.g., the liver. Recently,
      drug delivery strategies involving the use of nanoplatforms surface decorated
      with unique biomolecules have demonstrated their potential in concentrating the
      chemotherapy agent specifically into the malignant cells. This review will be
      focused on the analysis of the current state of the art and future perspectives
      of such passive and active targeting strategies based on the enhanced
      permeability and retention effect and on a ligand-mediated transport,
      respectively. Special attention will be given to the use of these surface
      functionalized nanocarriers to overcome multi-drug resistances in cancer cells.

PMID- 22612704
TI  - Drug delivery to inflammation based on nanoparticles surface decorated with
      biomolecules.
AB  - Anti-inflammatory molecules often display little affinity for inflamed tissues,
      leading to low accumulation into this site of action (and inefficiency), and high
      incidence of severe side effects. To face the problem, numerous strategies have
      been proposed, i.e., chemical modifications to the drug molecule, and engineering
      of drug nanocarriers. The later approach to the problem can result in optimized
      drug biodistribution and concentration into the target region, thus enhancing the
      anti-inflammatory effect while reducing the associated drug toxicity. Such
      nanoparticulate systems offer remarkable possibilities when they are made of
      biodegradable polymers, lipid-based structures, and/or inorganic particles.
      Recent advances in the field have been devoted to the optimization of the in vivo
      fate and effectiveness of these drug nanocarriers, e.g., passive targeting
      strategies based on the functionalization of nanoparticle surface with special
      biomolecules. In this contribution, we analyze the possibilities and future
      perspectives of nanoparticle therapy in inflammatory processes.

PMID- 22612703
TI  - Drug targeting to infectious diseases by nanoparticles surface functionalized
      with special biomolecules.
AB  - The potential to deliver nanoparticles directly into the targeted cells is
      important in the therapeutic applications for infectious diseases. The
      possibility of therapeutic agent being attached to the nanoparticles by chemical
      modification has provided a novel drug delivery option. Interestingly, the
      discovery of carbon nanotubes and graphene has given an excellent imaging and
      therapeutic agent for the biomedical applications. In spite of continuous
      advancement in pharmaceutical drug delivery viz. micelles, vesicles, liquid
      crystals, etc., during the past decades, their prohibitive production has limited
      their use. Nanomaterials with their properties of biodegradation, equal
      biodistribution, mass production, and long time storage make them attractive
      alternatives for future biomedical applications. Nanoparticles surface
      functionalized with specific biomolecules based drug delivery has driven new
      direction for modulating the pharmacokinetics, pharmacodynamics, biorecognition,
      and increasing the efficacy of targeted drugs. These new strategies are likely to
      minimize drug degradation and loss, increase drug availability, and opens up new
      vistas for drug delivery.

PMID- 22612705
TI  - Polysaccharide-based nanoparticles: a versatile platform for drug delivery and
      biomedical imaging.
AB  - Polysaccharide-based nanoparticles have attracted interest as carriers for
      imaging and therapeutic agents because of their unique physicochemical
      properties, including biocompatibility and biodegradability. In addition, the
      functional groups of the polysaccharide backbone allow facile chemical
      modification to develop nanoparticles with diverse structures. Some
      polysaccharides have the intrinsic ability to recognize specific cell types,
      facilitating the design of targeted-drug delivery systems through receptor
      mediated endocytosis. The main objective of this review is to provide an overview
      of various polysaccharide-based nanoparticles and to highlight the recent efforts
      that have been made to improve the characteristics of polysaccharide-based
      nanoparticles for drug delivery and biomedical imaging.

PMID- 22612706
TI  - Novel gb(3) isoforms detected in urine of fabry disease patients: a metabolomic
      study.
AB  - Fabry disease is characterized by the accumulation of globotriaosylsphingosine
      (lyso-Gb(3)) and globotriaosylceramide (Gb(3)) in biological fluids and tissues.
      Metabolomic studies recently undertaken by our group, showed the presence of
      novel plasma and urine lyso-Gb(3)-related analogs in male and female Fabry
      patients. These analogs are distinguished by differences in structure of the
      sphingosine moiety. The principal aim of this study was to evaluate the
      possibility of detecting other Fabry disease biomarkers structurally related to
      Gb(3). A time-of-flight mass spectrometry metabolomic approach, focusing on mass
      to-charge (m/z) ratios from 1000 to 1200 Da, was devised. This m/z window
      corresponds to the isoforms and potential analogs of Gb(3). Five different
      categories of Gb(3)- related isoforms/analogs were detected: Gb(3)-related
      isoforms with saturated fatty acids, methylated Gb(3)-related isoforms, Gb(3)
      related isoforms/analogs with one double bond, Gb(3) analogs with hydrated
      sphingosine, and Gb(3)-related isoforms/analogs with two double bonds. A
      secondary objective was to elucidate the relationship between Gb(3) and lyso
      Gb(3). The methylation observed on Gb(3)-related analogs was not detected on lyso
      Gb(3). We speculate that the methylated Gb(3) may be an intermediate compound in
      the deacylation of Gb(3) to generate the lyso-Gb(3) molecule. We are in the
      process of devising a quantification methodology for these methylated Gb(3)
      related analogs in Fabry patients to try to understand the underlying biochemical
      mechanisms involved in this complex disease.

PMID- 22612707
TI  - Melatonin, a natural programmed cell death inducer in cancer.
AB  - Melatonin, an indolamine derived from the amino-acid tryptophan, participates in
      diverse physiological functions and has great functional versatility related to
      the regulation of circadian rhythms and seasonal behaviour, sexual development,
      retinal physiology, tumour inhibition, as an antioxidant, immunomodulatory and
      anti-aging properties. In relation to its oncostatic properties, there is
      evidence that tumor initiation, promotion or progression may be restrained by the
      night-time physiological surge of melatonin in the blood or extracellular fluid.
      In addition, depressed nocturnal melatonin concentrations or nocturnal excretion
      of the main melatonin metabolite, 6-sulfatoxymelatonin, were found in individuals
      with various tumor types. In the majority of studies, melatonin was shown to
      inhibit development and/or growth of various experimental animal tumors and some
      human cell lines in vitro. Many tumors do not respond to drug treatment due to
      their resistance to undergo apoptosis thereby contributing to the development of
      cancer. Thus, given the importance of the apoptotic program in cancer treatment,
      the role of melatonin in influencing apoptosis in tumor cells attracted attention
      because it seems that it actually promotes apoptosis in most tumor cells, in
      contrast to the obvious inhibition of apoptotic processes in normal cells. Thus,
      this paper is also intended to provide to the reader an up-date of all the
      researches that have been carried out to date, which investigate the proapoptotic
      effects of melatonin in experimental preclinical models of cancer (in vitro and
      in vivo) and the underlying proposed action mechanism of this effects. If
      melatonin uniformly induces apoptosis in cancer cells, the findings could have
      important clinical implications to improve the quality of live while preventing
      the appearance of cancer.

PMID- 22612708
TI  - Palladacycles as antimicrobial agents.
AB  - This review article deals with the structure activity relationship (SAR) for a
      variety of palladacycles in biomedical applications. Moreover, the types of
      antibacterial, antifungal, antimycobacterial and antiprotozoal (antiamoebic and
      antitrypanosomal) activities will vary considerably from one country to another.
      Therefore, all efforts will be required to face such a vast diversity of
      problems. This study gives an up to date overview of the antibacterial,
      antifungal, antimycobacterial and antiprotozoal chemistry of the palladium group
      elements with an emphasis on the new strategies used in the development of new
      antibacterial agents. Methodologies for application of bulky aromatic or
      aliphatic nitrogen ligands, chiral organic moieties, chelates containing other
      donor atoms than nitrogen, and biologically active ligands in the design of
      agents analogous to palladacycles are presented. Therefore, the use of
      palladacycles in medicinal chemistry is interesting as potential application in
      the biological properties with less toxic drugs compounds..

PMID- 22612709
TI  - Boronate can be the fluorogenic switch for the detection of hydrogen peroxide.
AB  - Hydrogen peroxide (H(2)O(2)) has entrapped the abundant concern of numerous
      researchers in the cutting edge of chemistry, biology and medicine since it is
      thought to be associated with various biological and pathological conditions.
      Fluorescent probes are the promising tools for the detection and understanding of
      the physiological roles of H(2)O(2), considering that they are able to provide
      spatial and temporal information about target biomolecules in living cells.
      Nevertheless, the existent fluorescent probes have low selectivity and
      sensitivity on discerning H(2)O(2). This review would like to demonstrate a
      comprehensive examination on the design, recognition, and performance of state-of
      the-art boronate-based fluorogenic switch for the detection of H(2)O(2), a field
      in which remarkable improvements have been accomplished over the last decade.

PMID- 22612710
TI  - Nonanolides of natural origin: structure, synthesis, and biological activity.
AB  - Naturally occurring nonanolides (synonym decanolides) are a large family of
      secondary metabolites with an interesting 10- membered macrolide subunit.
      Metabolites of the nonanolide family have been found to have various biological
      activities, including cytotoxic, phytotoxic, antimalarial, antifungal,
      antibacterial, and antimicrofilament activities. An early review of the chemistry
      and bioactivity of nonanolides was presented in 1996, covering the literature
      published between 1975 and 1995. During the past decades, the broad spectrum of
      bioactivity and the intriguing structure of the medium-sized ring in nonanolide
      analogues have continuously drawn the attention of biologists and natural product
      and synthetic chemists, resulting in a great number of publications. This review
      summarizes in whole the recent progress in the field of the nonanolides of
      natural origin, aiming to give the readers a brief view of the compounds,
      concerning their natural occurrence, structural elucidation, biological
      activities, total synthesis, and structure-activity relationships. The article
      covers the literature published in the period from the beginning of 1996 to July
      2011.

PMID- 22612711
TI  - Chemical engineering of nanocarrier surfaces for an efficient drug delivery to
      severe diseases.

PMID- 22612712
TI  - Prevalence versus incidence.

PMID- 22612713
TI  - An unusual cause of ulcer.

PMID- 22612714
TI  - A Preliminary Investigation of NSCL/P Plasma and Urine in Guizhou Province in
      China Using NMR-Based Metabonomics.
AB  - Objective : To assess the feasibility of metabonomics in clinical studies. This
      is a pilot study introducing nuclear magnetic resonance (NMR)-based metabonomics
      to elucidate and compare the metabolism of patients with nonsyndromic cleft lip
      and/or palate (NSCL/P) and children without orofacial clefts. Methods : High
      resolution (1)H NMR spectroscopy was performed on plasma and urine samples
      obtained from NSCL/P and healthy children. The (1)H NMR spectra were further
      analyzed with principal component analysis. Results : Compared to the control
      group, the level of low-molecular-weight metabolites in plasma such as asparagine
      was higher in NSCL/P patients, while arginine, lysine, acetate, lactate, proline,
      glutamine, pyruvate, creatinine, choline, and beta-glucose were lower. The
      carnitine, citrate, and formate excretion in urine appeared to be higher in the
      healthy children, while the NSCL/P group excreted higher concentrations of
      aspartic acid and phenylalanine in urine. Conclusion : The present study clearly
      demonstrated the great potential of NMR-based metabonomics in elucidating NSCL/P
      plasma metabolism and the possible application of this technology in clinical
      diagnosis and screening. 

PMID- 22612715
TI  - Traffic optimization: a new way for air pollution control in China's urban areas.

PMID- 22612716
TI  - Sex-hormone-binding globulin early in pregnancy for the prediction of severe
      gestational diabetes mellitus and related complications.
AB  - AIMS:  The aim of this study was to evaluate the predictive value of sex-hormone
      binding globulin (SHBG) for the diagnosis of gestational diabetes mellitus (GDM),
      and to clarify the association between SHBG levels and GDM
      complications/medication requirements. MATERIAL AND METHODS: Among the
      participants (n = 93) who provided blood samples between 13 and 16 weeks'
      gestation, 30 cases subsequently developed GDM. Complications and medical
      interventions were noted. The best cut-off point of SHBG and diagnostic
      performance were calculated. RESULTS: The mean age was 28.45 +/- 5.0 years. SHBG
      levels were lower in the GDM group (n = 30) when compared with non-GDM (n = 63)
      cases (<0.01). Among the GDM women, SHBG was lower in the insulin therapy group
      (n = 15) compared with medical nutritional therapy alone (n = 15) (P < 0.01). A
      good predictive accuracy of SHBG was found for GDM requiring insulin therapy
      (area under the curve: 0.866, 95% confidence interval: 0.773-0.959). An SHBG
      threshold for 97.47 nmol/L had a sensitivity of 80.0%, specificity 84.6%,
      positive predictive value 50.0% and negative predictive value 95.7%. The
      calculated odds ratio for SHBG < 97.47 nmol/L was 12.346 (95% confidence
      interval: 1.786-83.33). CONCLUSIONS:  SHBG is valuable for screening women early
      in pregnancy for GDM risk; however, a standard assay for analyses and a threshold
      level of serum SHBG for a constant gestational week has to be determined.

PMID- 22612717
TI  - Interval, blocking, and marking effects during the development of schedule
      induced drinking in rats.
AB  - Schedule-induced drinking (SID) can occur when food-deprived rats are given
      access to water while receiving pellets on an intermittent reinforcement
      schedule. These conditions can increase water intake excessively. The possible
      role of adventitious reinforcement of postpellet drinking was assessed by testing
      whether response-reinforcer contiguity, the relative predictiveness of a
      response, and whether it is marked are important in the development of SID. Rats
      exposed to a short interpellet interval acquired SID most rapidly, with this
      acquired drinking response maintained when animals were transferred to a longer
      interpellet interval, thus indicating an easy-to-hard effect (Experiment 1).
      Further experiments demonstrated that a stimulus (a brief-flashing house light)
      occurring prior to pellet delivery could block the acquisition of SID (Experiment
      2), while a lick-contingent tone, intended to increase the associability of this
      response, produced more rapid acquisition of SID (Experiment 3). Analysis of lick
      distributions revealed that licking became concentrated in the first half of an
      interpellet interval only after several sessions. Overall, the results indicated
      that similar factors affect the acquisition of both SID and instrumental
      conditioning with delayed reinforcement, as is consistent with a superstitious
      conditioning account of SID development.

PMID- 22612718
TI  - Changes in the site distribution of common melanoma subtypes in Queensland,
      Australia over time: implications for public health campaigns.
AB  - BACKGROUND: An examination of melanoma incidence according to anatomical region
      may be one method of monitoring the impact of public health initiatives.
      OBJECTIVES:   To examine melanoma incidence trends by body site, sex and age at
      diagnosis or body site and morphology in a population at high risk. MATERIALS AND
      METHODS:   Population-based data on invasive melanoma cases (n = 51473) diagnosed
      between 1982 and 2008 were extracted from the Queensland Cancer Registry. Age
      standardized incidence rates were calculated using the direct method (2000 world
      standard population) and joinpoint regression models were used to fit trend
      lines. RESULTS:   Significantly decreasing trends for melanomas on the trunk and
      upper limbs/shoulders were observed during recent years for both sexes under the
      age of 40 years and among males aged 40-59years. However, in the 60 and over age
      group, the incidence of melanoma is continuing to increase at all sites (apart
      from the trunk) for males and on the scalp/neck and upper limbs/shoulders for
      females. Rates of nodular melanoma are currently decreasing on the trunk and
      lower limbs. In contrast, superficial spreading melanoma is significantly
      increasing on the scalp/neck and lower limbs, along with substantial increases in
      lentigo maligna melanoma since the late 1990s at all sites apart from the lower
      limbs. CONCLUSIONS:   In this large study we have observed significant decreases
      in rates of invasive melanoma in the younger age groups on less frequently
      exposed body sites. These results may provide some indirect evidence of the
      impact of long-running primary prevention campaigns.

PMID- 22612719
TI  - Paradoxical change in atrial fibrillation dominant frequencies with baroreflex
      mediated parasympathetic stimulation with phenylephrine infusion.
AB  - INTRODUCTION: Parasympathetic stimulation is known to promote atrial fibrillation
      (AF) through shortening of atrial refractory periods. We hypothesized that
      baroreflex-mediated parasympathetic stimulation via phenylephrine (PE) infusion
      would increase AF rate as measured by dominant frequency (DF). METHODS AND
      RESULTS: The protocol was performed in 27 patients (24 M, 59 +/- 1 years old)
      prior to AF ablation. For 10 patients in AF, PE was infused until systolic blood
      pressure increased >=30 mmHg. Electrograms were recorded in the left atrium
      before and after PE. DFs of each recording were calculated offline. Atrial
      effective refractory periods (ERPs) were measured before and after PE in 11
      patients who were in sinus rhythm during the procedure. DFs were also measured in
      6 patients in AF before and after complete parasympathetic blockade with atropine
      (0.04 mg/kg). PE resulted in increased RR intervals during sinus rhythm (1,170 +/
      77 to 1,282 +/- 85 ms, P = 0.03) and AF (743 +/- 32 to 826 +/- 30 ms, P = 0.03),
      consistent with parasympathetic effect on the sinus and AV nodes, respectively.
      DFs were decreased by PE in the left atrium (6.2 +/- 0.2 to 6.0 +/- 0.2 Hz, P =
      0.004). Correspondingly, atrial ERPs significantly increased from 218 +/- 13 to
      232 +/- 11 ms (P = 0.04). Atropine resulted in a decreasing trend in DF in the
      left atrium (5.9 +/- 0.1 to 5.8 +/- 0.1 Hz, P = 0.07). CONCLUSIONS: Despite
      baroreflex-mediated parasympathetic effect, PE produced a slowing of AF along
      with lengthening of ERP, while parasympathetic blockade also slowed DF. It is
      therefore likely that the direct and indirect adrenergic effects of PE on atrial
      electrophysiology are more prominent than its parasympathetic effects.

PMID- 22612721
TI  - Test-retest reliability of the functional mobility assessment (FMA): a pilot
      study.
AB  - PURPOSE: Functional mobility is necessary to perform activities of daily living
      and for community participation for everyone, but especially important for
      persons with disabilities (PWD). Therefore, functional mobility requires reliable
      measurement of consumer satisfaction and functional changes. The functional
      mobility assessment (FMA) instrument is a self-report outcomes tool designed to
      measure effectiveness of wheeled mobility and seating (WMS) interventions for
      PWD. This study examined the test-retest reliability of the FMA, and the
      stability of self-reported performance items. METHOD: A repeated-measures cohort
      study was conducted at the Center for Assistive Technology, at the University of
      Pittsburgh Medical Center. Participants (n = 41) completed an initial FMA
      questionnaire, and were re-administered the questionnaire within 7-21 days of the
      first questionnaire completion. The study sample included 20 participants who
      were non-WMS users but in the process of being evaluated for a device and 21
      participants who were existing WMS users. Intra-Class Correlation coefficients
      (ICC) were computed to determine agreement between the two scores. RESULTS: Test
      retest reliability scores for all items and participants were above the
      acceptable value for a clinical assessment tool (>=0.80). Responses on the FMA of
      Existing WMS users and non-WMS users did not differ significantly at test or
      retest. CONCLUSIONS: Results indicate that the FMA was a reliable and stable tool
      for assessing the functional performance of individuals who use or need WMS
      interventions.

PMID- 22612720
TI  - Impact of sunlight on the age of onset of bipolar disorder.
AB  - OBJECTIVE: Although bipolar disorder has high heritability, the onset occurs
      during several decades of life, suggesting that social and environmental factors
      may have considerable influence on disease onset. This study examined the
      association between the age of onset and sunlight at the location of onset.
      METHOD: Data were obtained from 2414 patients with a diagnosis of bipolar I
      disorder, according to DSM-IV criteria. Data were collected at 24 sites in 13
      countries spanning latitudes 6.3 to 63.4 degrees from the equator, including data
      from both hemispheres. The age of onset and location of onset were obtained
      retrospectively, from patient records and/or direct interviews. Solar insolation
      data, or the amount of electromagnetic energy striking the surface of the earth,
      were obtained from the NASA Surface Meteorology and Solar Energy (SSE) database
      for each location of onset. RESULTS: The larger the maximum monthly increase in
      solar insolation at the location of onset, the younger the age of onset
      (coefficient= -4.724, 95% CI: -8.124 to -1.323, p=0.006), controlling for each
      country's median age. The maximum monthly increase in solar insolation occurred
      in springtime. No relationships were found between the age of onset and latitude,
      yearly total solar insolation, and the maximum monthly decrease in solar
      insolation. The largest maximum monthly increases in solar insolation occurred in
      diverse environments, including Norway, arid areas in California, and Chile.
      CONCLUSION: The large maximum monthly increase in sunlight in springtime may have
      an important influence on the onset of bipolar disorder.

PMID- 22612722
TI  - Refining definitions of periodontal disease and caries for prediction models of
      incident tooth loss.
AB  - AIM: To assess the suitability of different definitions of caries and
      periodontitis for inclusion in tooth loss prediction models. MATERIALS AND
      METHODS: The Study of Health in Pomerania (SHIP) is a population-based cohort
      study conducted in 1997-2001 (SHIP-0) and 2002-2006 (SHIP-1). This sample
      comprised 2,780 subjects aged 20-81 years with complete information on dental and
      periodontal status [DMFS status, clinical attachment loss (CAL) and probing depth
      (PD)]. Analyses on five-year tooth loss were limited to half-mouth data. RESULTS:
      The predictive value of tested definitions was markedly age- and gender
      dependent: in 20-39-aged men, the number of decayed or filled surfaces best
      predicted the number of lost teeth, whereas in young women CAL>=4 mm performed
      best. In older subjects, periodontal definitions were superior to caries
      definitions: mean CAL performed best in 40-59-year olds, whereas AL- or PD
      related definitions predicted best in 60-81-year olds. On tooth level, mean CAL
      was the superior definition to assess 5-year incident tooth loss in all strata
      except for young men. CONCLUSIONS: Caries parameters best predicted incident
      tooth loss in men aged 20-39 years; in the intermediate and oldest age group and
      in young women, mean AL was most informative. Therefore, prediction models need
      to be developed for different age and gender groups.

PMID- 22612723
TI  - Combination therapy of Western drugs and herbal medicines: recent advances in
      understanding interactions involving metabolism and efflux.
AB  - INTRODUCTION: While complementary and alternative medicine markets prosper with
      an increasing number of consumers of herbal medicines, there is an associated
      likelihood for herb-drug interactions to occur. Modulation of the activity of
      metabolic enzymes and/or active transporters by chemical constituents of herbal
      medicines may influence the therapeutic outcomes of coadministered allopathic
      medicines due to changes in their pharmacokinetic profiles. Although valuable
      information on herb-drug interactions is obtained by in vitro studies, such as
      the mechanisms of interaction, clinical significance of interactions is
      ultimately demonstrated by in vivo data. AREAS COVERED: The authors outline the
      mechanisms of herb-drug pharmacokinetic interactions briefly and discuss
      pharmacokinetic interactions between different therapeutic classes of Western
      drugs and herbal medicines. Furthermore, the authors also discuss herb-drug
      interactions from both in vitro and in vivo studies with specific focus on recent
      findings. EXPERT OPINION: Basic and clinical researches have contributed to the
      comprehension of the underlying mechanisms involved as well as the practical
      implications of herb-drug interactions. This provides a foundation for
      development of guidelines to inform patients about herb-drug interactions that
      can affect their health.

PMID- 22612724
TI  - Comparative analysis of P2-type remnant prophage loci in Xenorhabdus bovienii and
      Xenorhabdus nematophila required for xenorhabdicin production.
AB  - The xnp1 remnant P2-type prophage of Xenorhabdus nematophila produces
      xenorhabdicin that is active against closely related species. Xenorhabdicin had
      not been characterized previously in other Xenorhabdus species. Here, we show
      xenorhabdicin production in six different strains of Xenorhabdus bovienii. The
      sequenced genome of X. bovienii SS-2004 was found to possess a highly conserved
      remnant P2-type cluster (xbp1). Inactivation of the xbpS1 sheath gene resulted in
      loss of bacteriocin activity, indicating that the xbp1 locus was required for
      xenorhabdicin production. xbp1 and xnp1 contain a CI-type repressor, a dinI gene
      involved in stabilization of ssDNA-RecA complexes and are inducible with
      mitomycin C, suggesting that both loci are regulated by cleavage of the CI
      repressor. Both xnp1 and xbp1 lack typical P2-type lysis genes but contain a
      predicted endolysin gene (enp) that may be involved in cell lysis. The main tail
      fibers of xnp1 and xbp1 are mosaic structures with divergent C-terminal regions
      suggesting they differ in host specificity. Several genes encoding C-terminal
      tail fiber fragments are present in the same position in xnp1 and xbp1.
      Recombination between the main fiber genes and the C-terminal fragments could
      potentially expand the host range specificity of xenorhabdicin in the respective
      strains.

PMID- 22612725
TI  - Thermal transport in three-dimensional foam architectures of few-layer graphene
      and ultrathin graphite.
AB  - At a very low solid concentration of 0.45 +/- 0.09 vol %, the room-temperature
      thermal conductivity (kappa(GF)) of freestanding graphene-based foams (GF),
      comprised of few-layer graphene (FLG) and ultrathin graphite (UG) synthesized
      through the use of methane chemical vapor deposition on reticulated nickel foams,
      was increased from 0.26 to 1.7 W m(-1) K(-1) after the etchant for the
      sacrificial nickel support was changed from an aggressive hydrochloric acid
      solution to a slow ammonium persulfate etchant. In addition, kappa(GF) showed a
      quadratic dependence on temperature between 11 and 75 K and peaked at about 150
      K, where the solid thermal conductivity (kappa(G)) of the FLG and UG constituents
      reached about 1600 W m(-1) K(-1), revealing the benefit of eliminating internal
      contact thermal resistance in the continuous GF structure.

PMID- 22612726
TI  - En plaque foramen magnum meningiomas: rare presentations.
AB  - Only 1.8-3.2% of all meningiomas are located at foramen magnum (FM). As these
      tumours are indolent, there occurs a long interval between onset of symptoms and
      diagnosis. This diagnostic delay may get accentuated, if unusual clinical
      features or radiological features are seen. The authors present two cases of FM
      meningiomas, with rare radiological features, one with intense bony hyperostosis
      and another with circumferentially, constricting en-plaque meningioma.

PMID- 22612727
TI  - Facilitating children's contributions in clinic? Findings from an in-depth
      qualitative study with children with Type 1 diabetes.
AB  - AIMS: There is a policy drive for children to contribute more directly in clinic
      visits. However, this has yet to be routinely achieved in practice and relatively
      little is known to date about younger children's views of their illness and care.
      This in-depth qualitative study set out to explore the experiences of children 10
      years or younger living with Type 1 diabetes. METHODS: The sample of 17 children
      was self-selecting from a population of 140 children under 11 years receiving
      treatment for Type 1 diabetes at two outpatient clinics in a large, multicultural
      city. Fieldwork comprised home visits, discussion groups and observation in
      outpatient clinics. RESULTS: Children's strong experiential understandings of
      their condition, the impact of their social position on experiences of care and
      their active role in maintenance of the regimen were at odds with how they were
      positioned, and how the disease was discussed, in clinic. CONCLUSION: Findings
      have implications for facilitating children's contributions in clinic,
      understanding how ideas about children are reproduced in clinical settings and
      supporting clinicians to engage with the capacities and priorities of children
      living with long-term illness.

PMID- 22612728
TI  - Simultaneous decolorization and bioelectricity generation in a dual chamber
      microbial fuel cell using electropolymerized-enzymatic cathode.
AB  - Effect of cathodic enzymatic decolorization of reactive blue 221 (RB221) on the
      performance of a dual-chamber microbial fuel cell (MFC) was investigated.
      Immobilized laccase on the surface of a modified graphite electrode was used in
      the cathode compartment in order to decolorize the azo dye and enhance the oxygen
      reduction reaction. First, methylene blue which is an electroactive polymer was
      electropolymerized on the surface of a graphite bar to prepare the modified
      electrode. Utilization of the modified electrode with no enzyme in the MFC
      increased the power density up to 57% due to the reduction of internal resistance
      from 1000 to 750 Omega. Using the electropolymerized-enzymatic cathode resulted
      in 65% improvement of the power density and a decolorization efficiency of 74%.
      Laccase could act as a biocatalyst for oxygen reduction reaction along with
      catalyzing RB221 decolorization. Treatment of RB221 with immobilized laccase
      reduced its toxicity up to 5.2%. Degradation products of RB221 were identified
      using GC-MS, and the decomposition pathway was proposed. A discussion was also
      provided as to the mechanism of dye decolorization on the enhancement of the MFC
      performance.

PMID- 22612729
TI  - Retrospective evaluation of the effectiveness of epsilon aminocaproic acid for
      the prevention of postamputation bleeding in retired racing Greyhounds with
      appendicular bone tumors: 46 cases (2003-2008).
AB  - OBJECTIVES: To determine the frequency of delayed postoperative bleeding in
      retired racing Greyhounds with appendicular bone tumors undergoing limb
      amputations. To identify if administration of epsilon-aminocaproic acid (EACA)
      was effective on the prevention of postoperative bleeding. DESIGN: Retrospective
      study from December 2003 to December 2008. SETTING: Veterinary university
      teaching hospital. ANIMALS: Forty-six retired racing Greyhounds (RRGs) diagnosed
      with primary appendicular bone tumors that underwent limb amputation were
      included in the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Thirteen of 46 RRGs (28%) included in the study had delayed postoperative
      bleeding starting 48-72 h after surgery. Bleeding episodes included cutaneous,
      subcutaneous, and external bleeding that extended from the area of the surgical
      site that became widespread within hours, and that required administration of
      blood components. A paired t-test suggests that there was a significant decrease
      in PCV postoperatively for both dogs that bled and dogs that did not bleed (P <
      0.0001). Forty of 46 RRGs (86%) received either fresh frozen plasma (FFP) or EACA
      or both, for the prevention of postoperative bleeding. A logistic regression
      model determined that dogs that did not receive EACA were 5.7 times more likely
      to bleed than dogs that did receive EACA, when controlling for whether or not
      they received FFP (95% CI: 1.02-32.15, P = 0.047). CONCLUSION: This retrospective
      study suggests that preemptive postoperative administration of EACA appears to be
      efficacious in decreasing the frequency of bleeding in RRGs undergoing limb
      amputation; however, a prospective study is warranted to corroborate its
      effectiveness.

PMID- 22612730
TI  - Hemostats, sealants, and adhesives III: a new update as well as cost and
      regulatory considerations for components of the surgical toolbox.
AB  - The hemostat, sealant, and adhesive components of the surgical toolbox continue
      to evolve and enter clinical practice at a rapid rate. The goal of this
      comprehensive, sequential review is to update these components to include those
      now available (February 2012) as well as to explore cost and regulatory factors
      that impact the development and use of these materials. A unique system of
      definitions for organizing these components based on group, category, and class
      is used as a means of improving the understanding and appropriate use of these
      materials. The system will be used here to present the most recent additions to
      the toolbox, which are evaluated based on safety, efficacy, usability, and cost.
      These new additions include pooled human plasma fibrinogen and thrombin embedded
      in an equine collagen patch for cardiac surgical hemostasis, polyethylene glycol
      (PEG) and human serum albumin for lung surgical pneumostasis, modified PEG and
      trilysine amine for spinal sealing, octyl and butyl lactoyl cyanoacrylate for
      vascular sealing, and a variety of octyl and butyl cyanoacrylates with or without
      dyes and/or polyester mesh for skin closure with the creation of a bacterial
      barrier. The system of definitions will also be used to clarify key strategies in
      the current health care environment for reducing costs and for increasing
      understanding of Food and Drug Administration regulatory decisions for these
      materials.

PMID- 22612734
TI  - Male genital lichen sclerosus and hepatitis C.

PMID- 22612735
TI  - Axillary skin: biology and care.
AB  - In skin care, the axilla is a biologically unique site requiring specialized
      attention and care. This area of skin is often subject to hair removal
      techniques, such as shaving and plucking. These procedures damage the skin
      leading to erythema and dryness in the short term, and in some cases, post
      inflammatory hyperpigmentation (PIHP) in the long term. This study will (i)
      briefly review the biology and unique properties of axillary skin, and (ii)
      describe the characteristics of the irritation and damage induced by contemporary
      skin care habits and resolution of these responses by the use of efficacious skin
      moisturizing technology. With respect to the latter, we propose that there are
      five groups of compounds, defined according to their mechanism of action, which
      are particularly relevant to the care of damaged axillary skin.

PMID- 22612736
TI  - Allometric extrapolation of factors VII, VIII and IX clearance in children from
      adults.
AB  - BACKGROUND: There are situations where a pharmacokinetic (PK) study may not be
      possible in children, especially in neonates and infants. Under these
      circumstances, one would like to extrapolate PK parameters from adults or older
      children to neonates and infants. Allometric scaling is a method which can be
      used for PK extrapolation from adults to children. OBJECTIVES: The objective of
      this study was to evaluate the predictive performance of an allometric model for
      the prediction of clearance of three coagulation factors in children from adult
      clearance. METHODS: Clearance values for three coagulation factors (rVIIa, rVIII
      and rIX) for adults and children were obtained from the literature. The
      allometric model was developed from adult data and then the model was used to
      predict clearance of the coagulation factors in individual child. The predicted
      clearance value was then compared with the observed clearance value in that
      child. RESULTS: The results of the study indicated that the CL of the three
      coagulation factors tested in this study could be predicted with accuracy (<=30%
      prediction error) in most of the children from the allometric model developed
      from adults. CONCLUSIONS: The study indicated that allometric scaling could be
      applied to predict the CL of coagulation factors in children from adults with
      accuracy. The predicted clearance can then be used to select a dose to initiate a
      clinical trial (pharmacokinetics, safety and efficacy) in children.

PMID- 22612737
TI  - Novel SNP development and analysis at a NADP+ -specific IDH enzyme gene in a four
      species mixed oak forest.
AB  - Closely related Quercus species generally exhibit low levels of genetic
      differentiation despite their ecological and morphological differences. However,
      at a few so-called 'outlier' loci they seem to remain genetically distinct.
      Isocitrate dehydrogenases (IDH) are key enzymes involved in the metabolic pathway
      of the citrate cycle. IDH has also been characterised as an 'outlier' marker,
      significantly differentiating the closely related Q. robur and Q. petraea with
      the isozyme technique. This ability to differentiate the species was tested here
      at molecular level: 13 single nucleotide polymorphism (SNP) markers were
      identified and developed within a NADP(+) -specific IDH gene in Quercus spp. and
      applied as molecular markers in a four species mixed oak forest in eastern
      Europe, where Q. robur, Q. petraea, Q. pubescens and Q. frainetto naturally co
      exist. From the 13 developed SNPs, three groups were formed: non-synonymous,
      synonymous and non-coding SNPs. The levels of total gene diversity were moderate
      for all species investigated. The non-synonymous SNPs showed lower levels of gene
      diversity. Overall, the four closely related Quercus spp. were significantly
      differentiated (except Q. petraea with Q. frainetto). Analysis of non-random
      association of alleles revealed no clear physical clustering of the SNP sites in
      significant linkage disequilibrium (LD). However, separate LD analysis for each
      species showed a lower number of sites in significant LD for Q. robur than for
      the other species, possibly reflecting the history of the species in this
      specific geographical site and less efficient recombination effect due to the
      larger effective population size of Q. robur. Eleven statistically significant
      associations were found between seven SNPs and morphological traits that are
      commonly used to differentiate oak species.

PMID- 22612738
TI  - Management of acne scarring, part I: a comparative review of laser surgical
      approaches.
AB  - Acne scarring is the result of a deviation in the orderly pattern of healing and
      can have profound psychosocial implications for patients. While the most
      effective means of addressing acne scarring is to prevent its formation through
      good acne control, there are a number of therapeutic interventions that improve
      the appearance of acne scars. Many of these procedural modalities have flaws and
      are limited by operator skill and experience. Laser scar revision, on the other
      hand, is a precise, well tolerated procedure with clinically demonstrable
      efficacy and minimal adverse effects that may be used alone or in combination
      with other scar treatments. The last 20 years has seen a dramatic evolution in
      laser treatment of acne scars, spanning ablative and nonablative technologies, to
      the current popularity of fractional laser scar revision. Determining which laser
      system to use depends upon the type and severity of acne scarring, the amount of
      recovery a patient can tolerate, and the ultimate goals and expectations of each
      patient. The importance of proper acne scar classification, laser scar revision
      techniques, and the evidence that addresses each laser system is reviewed in this
      article.

PMID- 22612739
TI  - Anti citrullinated protein antibodies and mechanism of action of common disease
      modifying drugs--insights in pathomechanisms of autoimmunity.
AB  - The increasing understanding of autoimmune mechanisms continuously leads to new
      therapeutic targets and development of novel diagnostic tools in rheumatology. On
      the other hand, an improved comprehension of mechanisms of action of many drugs
      and the daily utilization in rheumatology leads to a better understanding of the
      underlying autoimmune processes. An example for the latter is Bcell depletion
      using anti-CD20 antibodies, which leads to the concept of B cells not only
      playing a role as antibody secreting cells but also as important cellular
      components of autoimmune processes, acting as antigen presenting and cytokine
      producing cells. Another example is the conventional disease modifying anti
      rheumatic drug methotrexate, which has also been used successfully in the clinic
      first and then, while trying to understand its mechanism of action, led to knew
      insights in autoimmune mechanisms e.g. revealing the strong anti-inflammatory
      potential of adenosine. But not only the mechanism of action of different drugs,
      but also the identification of antibodies against citrullinated proteins (ACPA)
      as a valuable diagnostic tool resulted in novel concepts regarding the
      pathophysiology of rheumatoid arthritis. The following review first explains the
      value of ACPA in the diagnosis of rheumatoid arthritis (RA) and then summarizes
      the application and mechanism of action of several important substances used in
      the management of autoimmune disorders. Based on these insights, the authors
      explain their understanding of the autoimmune process as a continuous repeat of
      autoantigen presentation - autoreactive effector cell activation - destruction of
      tissue - liberation of new autoantigens - and again autoantigen presentation,
      which closes the vicious circle.

PMID- 22612740
TI  - Biochemical markers of autoimmune diseases of the nervous system.
AB  - Biochemical biomarkers are important candidates for the diagnosis and prognosis
      of neurological diseases of autoimmune etiology, since they may reflect the
      presence, nature and intensity of certain immune responses caused by both genetic
      and environmental processes. Different body fluids such as cerebrospinal fluid
      (CSF), serum, urine, and tears have been used to identify useful biomarkers.
      Autoimmune neurological diseases associated with pathology of cell surface
      structures such as myasthenia gravis, Lambert-Eaton myasthenic syndrome,
      neuromyotonia, stiff person syndrome, limbic encephalitis, Guillain-Barre
      syndrome (GBS), and neuromyelitis optica (NMO) are amenable to serum antibody
      tests which can be used to support the diagnosis. In several of these disorders,
      new specific autoantibodies have been detected that are directed against proteins
      complexed with potassium channels in both the central and peripheral nervous
      system such as contactin-2 associated protein (Caspr2) or the protein leucine
      rich, glioma-inactivated 1 (LGI1). Recently, a number of central nervous system
      disorders like limbic encephalitis and multiple sclerosis (MS) have also been
      associated with the presence of specific serum autoantibodies. In MS and GBS CSF
      analysis is still essential to support the diagnosis and to rule out other
      diseases. We provide an overview over the widening field of autoimmune diseases
      of the central and peripheral nervous system and discuss the current state of
      biomarker research and its relevance for clinical practice.

PMID- 22612741
TI  - The ambivalent role of apoptosis in experimental autoimmune encephalomyelitis and
      multiple sclerosis.
AB  - Apoptosis is synonymous to programmed cell death, which occurs in response to a
      plethora of stimuli and employs a series of highly conserved mediators and
      pathways. Its ambivalent role in immunology is illustrated by the fact that this
      process not only serves homeostatic functions but also exerts harmful effects
      including tissue damage. This is particularly true for neuroinflammatory diseases
      such as multiple sclerosis (MS), the most frequent neurological disease to
      afflict adolescents in the western world. Considerable insight into the role of
      apoptosis in MS has been obtained by using its animal model experimental
      autoimmune encephalomyelitis (EAE). Experiments using the EAE model have revealed
      that cell death affects both infiltrating lymphocytes and CNS resident cells, and
      that it contributes to axonal injury as well as the resolution of inflammation.
      Furthermore, it was discovered that the molecules involved in inducing and
      regulating this process are the Fas-FasL system, pro- and anti-apoptotic Bcl-2
      family members, 'initiator' and 'effector' caspases, glucocorticoid hormones and
      various modulatory proteins. The variety of apoptotic mechanisms in combination
      with their often opposing effects on the disease course highlights the need for a
      detailed understanding of apoptosis in this context. In the future, this may pave
      the way to novel approaches aiming at interfering with the apoptotic process to
      prevent tissue damage or at intentionally inducing cell death in order to
      ameliorate the disease by deleting autoreactive lymphocytes.

PMID- 22612742
TI  - In vivo imaging of the diseased nervous system: an update.
AB  - Cellular in vivo imaging can reveal the induction, progression and resolution of
      nervous system pathology in real-time. In this review, we summarize recent
      research in the field to illustrate how in vivo imaging has enhanced our
      understanding of a variety of neurological conditions caused by trauma,
      degeneration, ischemia or inflammation. Finally, we look ahead and discuss how
      novel biosensors might help us to follow not only the cellular but also the
      molecular pathogenesis of neurological diseases in vivo.

PMID- 22612743
TI  - Neurodegeneration and neuroprotection in multiple sclerosis.
AB  - The damage of axons and neurons in multiple sclerosis (MS) is well recognised and
      correlates with neurological disability. The reasons leading to axonal and
      neuronal injury are diverse and possibly change from an inflammatory mediated
      mechanism to a neurodegenerative mechanism over the course of the disease. Acute
      axonal injury is associated with inflammation in the CNS and thus
      immunomodulatory treatments may also protect neurons from further damage.
      However, more effective immune treatments also bear the risk for severe side
      effects. Thus, neuroprotection will become more important to be combined with
      safe immunomodulation. Although several targets for neuroprotection have been
      identified experimentally, the translation into clinical treatments proves very
      difficult. Only few and small trials have investigated substances that may be
      neuroprotective, however, none had proven to have a substantial effect in MS
      patients. Clinical trials of remyelination, considered as a natural way of
      neuroprotection, were likewise not able to achieve clinical benefit. Thus, the
      development of a neuroprtective treatment in MS will be a major challenge in the
      decades to come.

PMID- 22612744
TI  - Therapeutic monitoring of immunotherapies in autoimmune diseases.
AB  - Immunosuppressive treatment still is an important element in the management of
      autoimmune mediated diseases. However, immunosuppressive therapy is often
      complicated by a narrow therapeutic index and high variability of treatment
      response. This review discusses the clinical management and monitoring strategies
      for the use of ciclosporin A, tacrolimus, azathioprine, mycophenolat mofetil,
      mitoxantrone and some monoclonal antibodies with focus on natalizumab.

PMID- 22612745
TI  - Autoimmune diseases in gastroenterology.
AB  - There are several different diseases in gastroenterology with an important role
      of immunological mechanisms in their pathogenesis. We know autoimmune diseases
      with immunological reactions against liver or pancreatic tissue. In addition
      there are diseases like chronic inflammatory bowel diseases representing
      inappropriate immunological reactions followed by inflammation and tissue
      destruction. The research of the last decade has contributed significantly to the
      understanding of the pathogenesis of diseases based on immunological mechanisms
      and consequently to the development of novel therapeutic strategies targeting
      molecules. Chronic inflammatory bowel diseases, autoimmune hepatitis, primary
      sclerosing cholangitis, primary biliary cirrhosis, autoimmune pancreatitis, and
      celiac disease are the most important diseases with immunological pathogenesis in
      Gastroenterology. Especially in chronic inflammatory bowel diseases ulcerative
      colitis and Crohn's disease with immunosuppressive drugs and monoclonal
      antibodies new preparations are used in therapy. Autoimmune pancreatitis was
      characterized as an own entity in the last years. Therefore, this review will
      focus on these diseases.

PMID- 22612746
TI  - Immune therapy of multiple sclerosis--future strategies.
AB  - Baseline disease-modifying therapies (DMTs) for multiple sclerosis (MS) include
      three different preparations of interferon-beta (IFN-beta) and glatiramer acetate
      (GA). These substances reduce relapse rates, side-effects are tolerated by most
      patients and - after more than 15 years of experience - the long-term safety
      profile for these drugs can be appraised as very good. In 2006, the therapeutic
      tool kit was augmented by the first monoclonal antibody, natalizumab, approved as
      monotherapy for treatment-refractory highly active MS. The restriction to these
      patient groups results from the rare, but fatal risk of JC virus-induced
      progressive multifocal leukoencephalopathy (PML). The first oral agent
      (fingolimod) was approved in 2010 for the United States and in 2011 for Europe.
      As a further option for therapy escalation the chemotherapeutic agent
      mitoxantrone is approved for non-responding relapsing-remitting MS (RRMS) or
      secondary progressive MS (SPMS). The use of mitoxantrone is limited by severe
      cardiotoxicity and the risk of treatment related acute leukemia. However, despite
      the fact that therapeutic options for MS have significantly been widened over the
      past decade new treatment options and more convenient modes of application are
      needed to enhance efficacy and improve adherence to therapy. This article will
      review recent developments in MS treatments focusing on oral agents (cladribine,
      fingolimod, BG00012, teriflunomide and laquinimod) and novel monoclonal
      antibodies (alemtumzumab, daclizumab, ocrelizumab, ofatumumab).

PMID- 22612747
TI  - Animal models in neurology: drawbacks and opportunities.
AB  - Animal models have been used widely in neurology since many decades. They have
      led to an improved understanding of the pathophysiological processes underlying
      frequent diseases as multiple sclerosis or Parkinson's disease and enabled the
      development of highly effective therapeutical approaches. Current developments,
      drawbacks and limitations of animal models in neurology are discussed with a
      special focus on the experimental autoimmune encephalomyelitis - model of
      multiple sclerosis.

PMID- 22612748
TI  - An inventory of short term and long term changes in gene expression under
      interferon beta treatment of relapsing remitting MS patients.
AB  - Multiple sclerosis (MS) is a chronic immune modulated disease of the central
      nervous system (CNS), characterized by inflammation, demyelination and axonal
      injury. Currently relapsing remitting type of MS patients are most commonly
      treated with immune- modulators like interferon beta (IFN beta) or glatiramer
      acetate (GA). However, while the majority of patients respond well to therapy
      others do not. Gene expression profiles in blood samples taken over the course of
      IFN beta treatment can document changes in the biology of the patients in
      response to the drug and disease activity. During the last decade quite a few of
      such studies profiling expression in response to IFN beta treatment had been
      done. Here, we combine the results of these studies to outline common
      differential expression patterns in peripheral blood mononuclear cells (PBMCs)
      over the course of time under IFN beta treatment. We set these profiles into the
      picture of current knowledge about IFN beta pathway, MS immunology and IFN beta
      mechanisms of action. IFN beta modulates hundreds of genes. In most of the
      studies the prominent ones like MX 1, OAS 1, and CXCL 10 had been found to be
      influenced by IFN beta drug treatment. We show examples of short term and long
      term induced expressional changes, up and down regulated genes (STAT1 and IL8),
      and explain how under drug treatment feedback loops of type I IFN (IFN alpha and
      IFN beta) regulated genes may be modulated and changes in expression patterns may
      result in cytological changes.

PMID- 22612750
TI  - Psychoneuroimmunology - psyche and autoimmunity.
AB  - Psychoneuroimmunology is a relatively young field of research that investigates
      interactions between central nervous and immune system. The brain modulates the
      immune system by the endocrine and autonomic nervous system. Vice versa, the
      immune system modulates brain activity including sleep and body temperature.
      Based on a close functional and anatomical link, the immune and nervous systems
      act in a highly reciprocal manner. From fever to stress, the influence of one
      system on the other has evolved in an intricate manner to help sense danger and
      to mount an appropriate adaptive response. Over recent decades, reasonable
      evidence has emerged that these brain-to-immune interactions are highly modulated
      by psychological factors which influence immunity and autoimmune disease. For
      several diseases, the relevance of psychoneuroimmunological findings has already
      been demonstrated.

PMID- 22612749
TI  - Use of intravenous immunoglobulin in the treatment of immune-mediated
      demyelinating diseases of the nervous system.
AB  - Intravenous immunoglobulins (IVIg) are used in treatment of a broad spectrum of
      diseases. Immunoglobulin replacement therapy is the standard treatment for
      immunodeficiencies with compromised humoural immunity. Use of this method as an
      immunomodulating therapy ranges from transplantation and treatment of autoimmune
      haematological diseases to treatment of various neuroimmunological clinical
      entities. Limited quantitative availability due to dependence on human donors as
      a source of IVIg, coupled with high treatment costs, make necessary a highly
      responsible and evidence-based approach with these agents. Discussion of the
      indications and currently valid recommendations on use of IVIg in treatment of
      immunomediated demyelinating diseases of the nervous system is based on existing
      clinical studies. We describe further neurological indications for use of IVIg as
      well as mechanisms of action and adverse effects of its use.

PMID- 22612751
TI  - Monoclonal antibodies in the treatment of neuroimmunological diseases.
AB  - Over the past 25 years, monoclonal antibodies (mAb) have become important
      elements in the therapeutic concepts for numerous clinical specialities,
      including oncology, gastroenterology, hemostaseology and endocrinology. One of
      the most dynamic fields of their use is the treatment of autoimmune diseases.
      Although the number of existing mAb interfering with the immune system has
      increased remarkably and many studies have yielded encouraging results in the
      treatment of neuroimmunological diseases, their clinical use is still limited
      compared with standard treatments. The only mAb which has been approved for a
      neuroimmunological disease by now is natalizumab for the treatment of relapsing
      remitting multiple sclerosis (RRMS). This article gives an overview on mAb that
      are currently in use or under investigation for treating neuroimmunological
      diseases like multiple sclerosis (MS), neuromyelitis optica (NMO), chronic
      inflammatory demyelinating polyneuropathy (CIDP), inclusion body myositis (IBM),
      dermatomyositis, polymyositis, opsoclonusmyoclonus syndrome (OMS), multifocal
      motor neuropathy (MMN), anti-myelin-glycoprotein neuropathy (Anti-MAG), stiff
      person syndrome and myasthenia gravis (MG).

PMID- 22612752
TI  - Immunological aspects of the complex regional pain syndrome (CRPS).
AB  - Limb trauma can lead to the development of a complex regional pain syndrome
      (CRPS). CRPS is a descriptive term of a variety of different symptoms. According
      to the current IASP-approved criteria, human CRPS can be diagnosed if a
      combination of signs is present: continuing pain and hyperalgesia,
      disproportionate to the initial trauma, skin temperature and colour asymmetry,
      sweating asymmetry, edema, decreased range of motion, and trophic changes. The
      diagnosis and treatment of human CRPS can be demanding and the pathophysiology
      underlying the disease is still under investigation. Immunological aspects are
      considered to play an important role in the development of CRPS. The impact of
      elevated pro-inflammatory cytokines systemically as well as locally, increased
      neurogenic inflammation and auto-antibodies in the pathophysiological development
      of CRPS are discussed in this review.

PMID- 22612753
TI  - Current immune therapies of autoimmune disease of the nervous system with special
      emphasis to multiple sclerosis.
AB  - Autoimmune diseases of the nervous system such as myasthenia gravis, inflammatory
      demyelinating polyneuropathies, multiple sclerosis and others are still not
      curable. Yet the introduction of modern immune therapies could significantly
      improve the prospects of many patients affected by these disorders. In addition
      to steroids and immunosuppression i.v. immunoglobulins are used for treatment of
      myasthenia gravis and chronic inflammatory demyelinating polyneuropathy.
      Interferons, glatiramer acetate, natalizumab and fingolimod are applied in
      multiple sclerosis. The ever-improving efficacy of the drugs has to be balanced
      against the increasing risk of possible severe adverse effects.

PMID- 22612754
TI  - Modern therapeutic strategies for autoimmune diseases.
AB  - Autoimmunity is an overreaction of immune competent cells to self structures
      resulting in an unwanted clinical outcome. Traditional therapeutic strategies,
      still relevant in many cases, involve broad acting immunosuppressants such as
      cyclophosphamide with the predictable attendant toxicity. More recent concepts
      include blockade of specifically defined targets such as TNF-alpha, with
      resulting immunomodulation and less toxicity. Both of these strategies require
      ongoing drug treatment of established disease. A long standing goal, not yet
      achieved, is the predictable induction of tolerance, obviating the need for
      chronic treatment. Experimental strategies to achieve this include pre-emptive
      (preclinical) treatment before chronification is established, total immune
      ablation and immune "resetting" and autoantigen immunisation.

PMID- 22612755
TI  - Management of spasticity in progressive multiple sclerosis: efficacy of repeated
      intrathecal triamcinolone acetonide administration.
AB  - Multiple sclerosis (MS) as a chronic disease presents a vast variability of
      neurological symptoms. Spasticity is one of the most common symptoms. The
      principle indication to treat spasticity is disability or handicap of
      capabilities. All pharmacological methods are attributed to a basic physical
      management. Different effective treatment schemes have been established.
      Nevertheless the value of intrathecal triamcinolone acetonid (TCA) in MS is still
      a controversial issue. Bearing in mind that only limited data are available and
      due to its invasive application form repeated TCA administration can be
      recommended as one therapy option in MS with a progressive clinical course and
      predominantly spinal symptoms.

PMID- 22612756
TI  - Paraneoplastic neurological syndromes--diagnosis and management.
AB  - Paraneoplastic neurological syndromes (PNS) are rare nervous system dysfunctions
      in cancer patients, which are not due to a local effect of the tumour or its
      metastases. PNS in adults are mainly associated with lung cancer, especially
      small cell lung cancer, lymphoma and gynaecological tumours. In some cases an
      overlapping of different clinical syndromes can be observed. Since autoantibodies
      directed against tumour and nervous system tissue can be observed, an autoimmune
      aetiology has been suspected in PNS patients. Currently, one group of patients
      exhibit surface-binding receptor or ion channel autoantibodies which are thought
      to be pathogenic and many of these patients respond well to immunotherapies.
      Another group of PNS is associated with highly specific autoantibodies directed
      against intracellular onconeuronal antigens. The latter group seem to be T-cell
      mediated and do not respond well to immunotherapies. The childhood PNS,
      especially the neuroblastoma-associated opsoclonus-myoclonus syndrome also
      respond to immunosuppressive therapies, plasmapheresis and intravenous
      immunoglobulins. The current review summarizes recent developments in
      physiopathology, diagnosis and treatment of paraneoplastic neurological
      syndromes.

PMID- 22612757
TI  - Diagnostics and therapy of antineutrophil cytoplasmic antibody (ANCA) associated
      vasculitides.
AB  - Granulumatosis with polyangiitis (wegener's)/GPA microscopic polyangiitis (MPA)
      and Churg Strauss syndrome (CSS) are primary systemic vasculitides which
      predominantly affect small vessels, showing a high association with a positive
      C/PR3-ANCA in GPA and P/MPO-ANCA in MPA, so called ANCA-associated vasculitides
      (AAV). The diagnostic work-up relies on an interdisciplinary approach including
      imaging techniques and laboratory tests in order to assess disease stage and
      extent. The golden standard remains the histological proof of a necrotizing,
      pauci-immune small vessel vasculitis, in GPA additionally non-caseating granuloma
      is found mainly in the respiratory tract. Treatment is adapted to disease stage
      and extent and relies on a combination of a cytotoxic plus a tapering regimen of
      glucocorticosteroids. Induction of remission in "early systemic" disease without
      organ- and life-threatening organ manifestations and a near normal kidney
      function can be achieved with methotrexate. In the generalized phase with
      significant renal dysfunction cyclophosphamide is the mainstay of therapy, in
      rapidly progressive glomerulonephritis with an imminent dialysis indication
      plasmapheresis is performed additionally. When remission is achieved, usually
      after 3-6 months of induction treatment, cyclophosphamide is switched to
      azathioprine as maintenance of remission drug. Alternative therapies are
      methotrexate provided the kidney function is normal or Leflunomide in the long
      term follow-up the relapse rate in ANCA-associated vasculitis is approximately
      50% in 5 years, irrespective of the drug used for maintenance treatment. The
      relapse rate is significantly higher in GPA than in MPA and CSS.

PMID- 22612760
TI  - Erratum.

PMID- 22612763
TI  - Upcoming New Feature in the Journal of Biomolecular Structure & Dynamics.

PMID- 22612758
TI  - The dermatology hospitalist: creating value by rapid clinical pathologic
      correlation in a patient-centered care model.
AB  - BACKGROUND: The active and continuous presence of dermatologists in hospitals has
      undergone continued involution over the past two decades. Our patient-centered,
      value-based dermatology hospitalist model describes an efficient system for the
      integration of the dermatologist in the hospital treatment team. METHODS: We
      describe five difficult inpatient cases to illustrate the value of dermatology
      intervention and clinical pathologic correlation in facilitating timely diagnosis
      and treatment. RESULTS: Prompt specialty evaluation and clinicopathologic
      correlation by hospital dermatologists led to decreased morbidity and the
      avoidance of delay in initiating definitive treatment. CONCLUSIONS: Efficient
      evaluation and clinicopathologic correlation by dermatology hospitalists are
      essential to hospitals that provide comprehensive care. This value-based model
      has the potential to produce better patient outcomes and greater satisfaction in
      both patients and other health care providers.

PMID- 22612765
TI  - Cost-effectiveness of an individually tailored oral health educational programme
      based on cognitive behavioural strategies in non-surgical periodontal treatment.
AB  - AIM: The aim of this cost-effectiveness analysis (CEA), performed from a societal
      perspective, was to compare costs and consequences of an individually tailored
      oral health educational programme (ITOHEP) based on cognitive behavioural
      strategies integrated in non-surgical periodontal treatment compared with a
      standard treatment programme (ST). MATERIAL AND METHODS: A randomized (n = 113),
      evaluator-blinded, controlled trial, with two different active treatments, was
      analysed with respect to their costs and consequences 12 months after non
      surgical treatment. Costs referred to both treatment costs and costs contributed
      by the patient. Consequences (outcome) were expressed as the proportion of
      individuals classified as having reached the pre-set criteria for treatment
      success after non-surgical treatment ("successful-NSPT"). RESULTS: More
      individuals in the ITOHEP group reached the pre-set criteria for treatment
      success than individuals in the ST group did. The CEA revealed an incremental
      cost-effectiveness of SEK1724 [?191.09; SEK9.02 = ?1 (January 2007)] per
      "successful-NSPT" case, of which treatment costs represented SEK1189 (?131.82),
      using the unit cost for a dental hygienist. CONCLUSION: The incremental costs per
      "successful-NSPT" case can be considered as low and strengthens the suggestion
      that an ITOHEP integrated into non-surgical periodontal treatment is preferable
      to a standardized education programme.

PMID- 22612766
TI  - Graphite nanoplatelets and Caenorhabditis elegans: insights from an in vivo
      model.
AB  - We evaluated the toxicity of graphite nanoplatelets (GNPs) in the model organism
      Caenorhabditis elegans. The GNPs resulted nontoxic by measuring longevity as well
      as reproductive capability end points. An imaging technique based on Fourier
      transform infrared spectroscopy (FT-IR) mapping was also developed to analyze the
      GNPs spatial distribution inside the nematodes. Conflicting reports on the in
      vitro antimicrobial properties of graphene-based nanomaterials prompted us to
      challenge the host-pathogen system C. elegans-Pseudomonas aeruginosa to assess
      these findings through an in vivo model.

PMID- 22612767
TI  - How decisions emerge: action dynamics in intertemporal decision making.
AB  - In intertemporal decision making, individuals prefer smaller rewards delivered
      sooner over larger rewards delivered later, often to an extent that seems
      irrational from an economical perspective. This behavior has been attributed to a
      lack of self-control and reflection, the nonlinearity of human time perception,
      and several other sources. Although an increasing number of models propose
      different mathematical descriptions of temporal discounting, the dynamics of the
      decision process behind temporal discounting are much less clear. In this study,
      we obtained further insights into the mechanisms of intertemporal decisions by
      observing choice action dynamics via a novel combination of continuously recorded
      mouse movements and a multiple regression approach. Participants had to choose
      between two hypothetical options (sooner/smaller vs. later/larger) by moving the
      mouse cursor from the bottom of the screen either to the top left or to the top
      right. We observed less direct mouse movements when participants chose
      later/larger rewards, indicating that participants had to overcome the attraction
      of the sooner/smaller reward first. Additionally, our results suggest that
      framing time information differently changes the weighting of value. We conclude
      that using a continuous process-oriented approach could further advance the
      understanding of intertemporal choice beyond the identification of the best
      fitted mathematical description of the discounting function by uncovering the way
      intertemporal decisions are performed.

PMID- 22612768
TI  - Developmental change in numerical estimation.
AB  - Mental representations of numerical magnitude are commonly thought to undergo
      discontinuous change over development in the form of a "representational shift."
      This idea stems from an apparent categorical shift from logarithmic to linear
      patterns of numerical estimation on tasks that involve translating between
      numerical magnitudes and spatial positions (such as number-line estimation).
      However, the observed patterns of performance are broadly consistent with a
      fundamentally different view, based on psychophysical modeling of proportion
      estimation, that explains the data without appealing to discontinuous change in
      mental representations of numerical magnitude. The present study assessed these 2
      theories' abilities to account for the development of numerical estimation in 5-
      through 10-year-olds. The proportional account explained estimation patterns
      better than the logarithmic-to-linear-shift account for all age groups, at both
      group and individual levels. These findings contribute to our understanding of
      the nature and development of the mental representation of number and have more
      general implications for theories of cognitive developmental change.

PMID- 22612769
TI  - The crosstalk hypothesis: why language interferes with driving.
AB  - Performing two cognitive tasks at the same time can degrade performance for
      either domain-general reasons (e.g., both tasks require attention) or domain
      specific reasons (e.g., both tasks require visual working memory). We tested
      predictions of these two accounts of interference on the task of driving while
      using language, a naturally occurring dual task. Using language and driving a
      vehicle use different perceptual and motor skills. As a consequence, a domain
      general explanation for interference in this dual task appears most plausible.
      However, recent evidence from the language processing literature suggests that
      when people use language with motor content (e.g., language about actions) or
      visual content (e.g., language about visible objects and events), they engage
      their motor and perceptual systems in ways specifically reflecting the actions
      and percepts that the language is about. This raises the possibility that
      language might interfere with driving for domain-specific reasons when the
      language has visual or motor content. To test this, we had participants drive a
      simulated vehicle while simultaneously answering true-false statements that had
      motor, visual, or abstract content. A domain-general explanation for interference
      would predict greater distraction in each of these three conditions compared with
      control, while a domain-specific explanation would predict greater interference
      in the motor and visual conditions. Both of these predictions were borne out but
      on different measures of distraction, suggesting that language-driven distraction
      during driving and dual tasks involving language in general may be the result not
      only of domain-general causes but also specific interference caused by linguistic
      content.

PMID- 22612770
TI  - Creating illusions of knowledge: learning errors that contradict prior knowledge.
AB  - Most people know that the Pacific is the largest ocean on Earth and that Edison
      invented the light bulb. Our question is whether this knowledge is stable, or if
      people will incorporate errors into their knowledge bases, even if they have the
      correct knowledge stored in memory. To test this, we asked participants general
      knowledge questions 2 weeks before they read stories that contained errors (e.g.,
      "Franklin invented the light bulb"). On a later general-knowledge test,
      participants reproduced story errors despite previously answering the questions
      correctly. This misinformation effect was found even for questions that were
      answered correctly on the initial test with the highest level of confidence.
      Furthermore, prior knowledge offered no protection against errors entering the
      knowledge base; the misinformation effect was equivalent for previously known and
      unknown facts. Errors can enter the knowledge base even when learners have the
      knowledge necessary to catch the errors.

PMID- 22612771
TI  - Too calloused to care: an experimental examination of factors influencing youths'
      displaced aggression against their peers.
AB  - People often displace their aggression against innocent targets. Notwithstanding
      the merits of previous research on displaced aggression, critical gaps remain.
      First, it is unclear whether and how situational and dispositional factors
      interact to influence displaced aggression. Moreover, it is unclear whether
      engaging in direct aggression increases or decreases displaced aggression. To
      address these gaps, the present experiment investigated how situational factors
      (provocateur availability, provocation intensity) and dispositional factors
      (callousness, trait aggressiveness) jointly influence displaced and direct
      aggression in male adolescents. Participants (N = 175, Mage = 13.1 years)
      completed a personal profile that was allegedly evaluated by peer judges. After
      randomly receiving mild or strong negative feedback, participants could aggress
      against these peer judges as well as against other innocent peers (direct and
      displaced aggression) or against innocent peers only (displaced aggression).
      Results showed that displaced aggression occurred only when the negative feedback
      was strong and participants could not retaliate directly. Higher levels of
      callousness specifically predicted more displaced (but not direct) aggression.
      However, the potentiating effects of callousness emerged only when the negative
      feedback was strong. This finding highlights the importance of examining
      disposition by situation interactions in displaced aggression research.

PMID- 22612772
TI  - Stronger discounting of external cause by action in human adults: evidence for an
      action-based hypothesis of visual collision perception.
AB  - When an actor performs an action on an external object, the actor feels that he
      or she is exerting a force on that object. By extension, when an observer views a
      collision between 2 objects, he or she is able to perceive the force that is
      exerted on the objects during the collision. The latter case is puzzling, as
      force is not a visual feature per se. In a series of 6 experiments, the present
      study aimed to clarify whether and how the experience of acting on an object
      influences causal impressions of collision. In the study, an external cause
      object and a participant's finger both made contact with an effect object, which
      subsequently started moving. Participants' ratings of causality revealed that
      causal impressions of the finger were stronger than those of the cause object
      (i.e., stronger discounting of the causality of the object by finger touch).
      Discounting was not due to the occasional earlier finger touches or attention
      distraction from the cause object. In addition, showing images of a finger touch
      to participants without having them undertake actual action did not result in the
      same discounted causality as would an actual action. These results are discussed
      in terms of the action-based hypothesis of collision perception, which holds that
      the impression of exertion of force when observing a collision event is derived
      from the mechanoreceptor experience of acting on an object.

PMID- 22612773
TI  - The effect of an isocentric reciprocating gait orthosis incorporating an active
      knee mechanism on the gait of a spinal cord injury patient: a single case study.
AB  - OBJECTIVE: The aim of this study was to identify the effect of induced knee
      flexion during gait on the kinematics and temporal-spatial parameters during
      walking by a patient with spinal cord injury (SCI) through the application of an
      isocentric reciprocating gait orthosis (IRGO) with a powered knee mechanism.
      METHODS: Two orthoses were considered and evaluated for an ISCI subject with a T8
      level of injury. An IRGO was initially manufactured by incorporating drop lock
      knee joints and was fabricated with custom molded AFOs to block ankle motion.
      This orthosis was also adapted with electrically-activated knee joints to provide
      active knee extension and flexion when disengaged. RESULTS: Walking speed, stride
      length and cadence were increased 37.5%, 11% and 26%, respectively with the new
      orthosis as compared to using the IRGO. The vertical and horizontal compensatory
      motions reduced compared to mechanical IRGO. At end of stance phase, knee joint
      flexion was 37.5 degrees  for the AKIRGO compared to 7 degrees  of movement when
      walking with the IRGO. The overall pattern of walking produced was comparable to
      that of normal human walking. CONCLUSION: Knee flexion during swing phase
      resulted in an improved gait performance and also reduction in compensatory
      motions when compared to a mechanical IRGO.

PMID- 22612774
TI  - Photodissociation of cobalt and nickel oxide cluster cations.
AB  - Cobalt and nickel oxide cluster cations, Co(x)O(y)(+) and Ni(x)O(y)(+), are
      produced by laser vaporization of metal rods in a pulsed nozzle cluster source
      and detected using time-of-flight mass spectrometry. The mass spectra show
      prominent stoichiometries of x = y for Co(x)O(y)(+) along with x = y and x = y -
      1 for Ni(x)O(y)(+). The cluster cations are mass selected and multiphoton
      photodissociated using the third harmonic (355 nm) of a Nd:YAG laser. Although
      various channels are observed, photofragmentation exhibits two main forms of
      dissociation processes in each system. Co(x)O(y)(+) dissociates preferentially
      through the loss of O(2) and the formation of cobalt oxide clusters with a 1:1
      stoichiometry. The Co(4)O(4)(+) cluster seems to be particularly stable.
      Ni(x)O(y)(+) fragments reveal a similar loss of O(2), although they are found to
      favor metal-rich fragments with stoichiometries of Ni(x)O(x-1). The Ni(2)O(+)
      fragment is produced from many parent ions. The patterns in fragmentation here
      are not nearly as strong as those seen for early or mid-period transition-metal
      oxides studied previously.

PMID- 22612775
TI  - African horse sickness in naturally infected, immunised horses.
AB  - To determine whether subclinical cases, together with clinical cases, of African
      horse sickness (AHS) occur in immunised horses in field conditions, whole blood
      samples were collected and rectal temperatures recorded weekly from 50
      Nooitgedacht ponies resident in open camps at the Faculty of Veterinary Science,
      University of Pretoria, Onderstepoort, during 2008-2010. The samples were tested
      for the presence of African horse sickness virus (AHSV) RNA by a recently
      developed real-time RT-PCR. It was shown that 16% of immunised horses in an AHS
      endemic area were infected with AHSV over a 2 year period, with half of these
      (8%) being subclinically infected. The potential impact of such cases on the
      epidemiology of AHS warrants further investigation.

PMID- 22612776
TI  - The association of physical examination abnormalities and carboxyhemoglobin
      concentrations in 21 dogs trapped in a kennel fire.
AB  - OBJECTIVE: To evaluate physical examination findings and their association with
      carboxyhemoglobin (COHb) concentrations in 21 dogs that were exposed to smoke
      during a kennel fire. SERIES SUMMARY: Twenty-one dogs were exposed to a kennel
      fire. Physical exam findings, presenting, and posttherapy COHb concentrations as
      well as therapeutic interventions were evaluated. COHb concentrations upon
      presentation were increased in all smoke inhalation exposed dogs. These dogs were
      compared to a small set of clinically normal staff-owned dogs who were not
      exposed to fire. Physical parameters significantly associated with higher COHb
      concentrations included lower body temperature, increased respiratory effort,
      abnormal respiratory auscultation, altered neurologic status, and length of
      hospital stay. Oxygen therapy resulted in a more rapid decline in COHb
      concentrations although 5 dogs still had mildly increased COHb concentrations 24
      hour postadmission. UNIQUE INFORMATION PROVIDED: This study describes the
      relationship of admitting clinical findings of dogs exposed to a kennel fire with
      their initial blood COHb concentrations. It also describes the resolution of
      increased COHb concentrations with use of oxygen therapy and hospitalization.
      Additionally, COHb concentrations for a control group of dogs was evaluated and
      compared to the dogs exposed to smoke inhalation.

PMID- 22612777
TI  - Effects of probiotics, probiotic DNA and the CpG oligodeoxynucleotides on
      ovalbumin-sensitized Brown-Norway rats via TLR9/NF-kappaB pathway.
AB  - The aim of the study was to investigate the effect of living probiotics,
      probiotic DNA and the synthetic oligodeoxynucleotides containing CpG motifs (CpG
      ODN) on both immune response and intestinal barrier function in ovalbumin
      sensitized rat and the underlying mechanisms. Brown-Norway rats were orally
      sensitized with ovalbumin, and living probiotics, probiotic DNA extraction,
      synthetic CpG-ODN or non-CpG ODN control was administered. In the living
      probiotics, probiotic DNA and CpG-ODN groups, the allergic response was
      significantly inhibited, the Th1/Th2 cytokine balance was shifted away from Th2
      side, the percentage of CD4(+) CD25(+high) Treg cells was increased, and the
      intestinal barrier function was improved. The levels of toll-like receptor (TLR)
      9 mRNA and nuclear factor (NF)-kappaB activity, as well as the IkappaB-alpha
      phosphorylation (p-IkappaB-alpha) was significantly increased in these three
      intervention groups compared with the OVA-positive group, whereas no such effects
      were found in the non-CpG ODN control group. These data show that the probiotic
      genomic DNA and the synthetic CpG-ODN was comparable with living probiotics in
      preventing food allergic response by immune modulation and intestinal barrier
      function enhancement, and the activation of TLR9/NF-kappaB signal pathway might
      be involved in this process.

PMID- 22612778
TI  - Outcomes and prognostic factors of cervical cancer after concurrent
      chemoradiation.
AB  - AIM: Concurrent chemoradiation (CCRT) is the standard treatment for locally
      advanced cervical cancer. This study was undertaken to evaluate the outcomes and
      the prognostic factors for cervical cancer after CCRT. MATERIAL AND METHODS: The
      medical records of 174 patients with International Federation of Gynecology and
      Obstetrics stage IB1-IVA who were treated at three affiliated hospitals of the
      Catholic University of Korea between January 1999 and December 2008 were reviewed
      and analyzed. Patients received pelvic radiotherapy with one of three regimens of
      cisplatin-based chemotherapy concurrently and high-dose rate brachytherapy. The
      radiation field was extended to include para-aortic lymph nodes, if necessary.
      RESULTS:  The median follow-up period was 29.5 months (range, 5-96 months). Using
      multivariate analysis, stage (P = 0.014), tumor size (P = 0.043), and clinical
      response (P = 0.001) had a significant effect on overall survival. Similarly,
      progression-free survival (PFS) was influenced by stage (P = 0.004), tumor size
      (P = 0.02), clinical response (P = 0.011), and normalized squamous cell carcinoma
      antigen level after CCRT (P = 0.007). The 5-year survival rates were 91.7%
      (standard error, 5.8%) for stages IB1-IIA, 71.5% (standard error, 7.8%) for stage
      IIB, 44.9% (standard error, 7.8%) for stage III, and 20.9% (standard error,
      12.0%) for stage IVA. A total of 151 out of 174 patients (86.8%) completed the
      planned treatment. Toxicities were manageable with supportive therapy.
      CONCLUSIONS: Cisplatin-based CCRT is well-tolerated. Good clinical response
      revealed a favorable correlation to survival. A maximal effort to achieve this
      goal might prolong survival in patients with cervical cancer.

PMID- 22612779
TI  - Bioreactor performance and quantitative analysis of methanogenic and bacterial
      community dynamics in microbial electrolysis cells during large temperature
      fluctuations.
AB  - The use of microbial electrolysis cells (MECs) for H(2) production generally
      finds H(2) sink by undesirable methanogenesis at mesophilic temperatures.
      Previously reported approaches failed to effectively inhibit methanogenesis
      without the addition of nongreen chemical inhibitors. Here, we demonstrated that
      the CH(4) production and the number of methanogens in single-chamber MECs could
      be restricted steadily to a negligible level by continuously operating reactors
      at the relatively low temperature of 15  degrees C. This resulted in a H(2) yield
      and production rate comparable to those obtained at 30  degrees C with less CH(4)
      production (CH(4)% < 1%). However, this operation at 15  degrees C should be
      taken from the initial stage of anodic biofilm formation, when the methanogenic
      community has not yet been established sufficiently. Maintaining MECs operating
      at 20  degrees C was not effective for controlling methanogenesis. The varying
      degrees of methanogenesis observed in MECs at 30  degrees C could be completely
      inhibited at 4 and 9  degrees C, and the total number of methanogens (mainly
      hydrogenotrophic methanogens) could be reduced by 68-91% during 32-55 days of
      operation at the low temperatures. However, methanogens cannot be eliminated
      completely at these temperatures. After the temperature is returned to 30 
      degrees C, the CH(4) production and the number of total methanogens can rapidly
      rise to the prior levels. Analysis of bacterial communities using 454
      pyrosequencing showed that changes in temperature had no a substantial impact on
      composition of dominant electricity-producing bacteria ( Geobacter ). The results
      of our study provide more information toward understanding the temperature
      dependent control of methanogenesis in MECs.

PMID- 22612780
TI  - Addressing the risk of bacterial contamination of platelets within the United
      States: a history to help illuminate the future.

PMID- 22612781
TI  - Identification and design of antimicrobial peptides for therapeutic applications.
AB  - Indiscriminate use of antibiotics has led to a rapid increase of antibiotic
      resistance among microbes which has increased the need to develop novel
      antimicrobial agents to fight various infectious diseases. Peptide antibiotics
      signify a novel class of therapeutic agents and have been isolated from a wide
      variety of multi-cellular organisms. Peptide antibiotics have shown broad
      spectrum antimicrobial activity and they not only kill different bacteria, but
      also kill various fungi, parasites, protozoans and cancerous cells. Peptides bear
      several properties that make them particularly attractive such as their small
      size, rapid activity and a low chance for development of resistance. Because of
      these distinct properties, the focus for research on antimicrobial peptides has
      increased tremendously in the recent years. Despite their potential, only
      selected cationic antimicrobial peptides have been able to enter in clinical
      trials. Therefore, there is a pressing need to develop new approaches to identify
      novel antimicrobial peptide therapeutics replacing conventional antibiotics.
      Recent findings strongly suggest that one can design a new generation of
      antimicrobials peptides with a wide range of systemic and topical applications
      against bacterial infections. In this review, we focus on the identification and
      design of novel antimicrobial peptides for therapeutic applications based on
      different approaches and strategies. This review also highlights some recent
      advances in the study of the molecular basis of anti-microbial activity in these
      peptides, their current pharmacological and clinical development and future
      directions and applications.

PMID- 22612782
TI  - Characterization of fiber-forming peptides and proteins by means of atomic force
      microscopy.
AB  - The atomic force microscope (AFM) is widely used in biological sciences due to
      its ability to perform imaging experiments at high resolution in a physiological
      environment, without special sample preparation such as fixation or staining. AFM
      is unique, in that it allows single molecule information of mechanical properties
      and molecular recognition to be gathered. This review sets out to identify
      methodological applications of AFM for characterization of fiber-forming proteins
      and peptides. The basics of AFM operation are detailed, with in-depth information
      for any life scientist to get a grasp on AFM capabilities. It also briefly
      describes antibody recognition imaging and mapping of nanomechanical properties
      on biological samples. Subsequently, examples of AFM application to fiber-forming
      natural proteins, and fiber-forming synthetic peptides are given. Here, AFM is
      used primarily for structural characterization of fibers in combination with
      other techniques, such as circular dichroism and fluorescence spectroscopy. More
      recent developments in antibody recognition imaging to identify constituents of
      protein fibers formed in human disease are explored. This review, as a whole,
      seeks to encourage the life scientists dealing with protein aggregation phenomena
      to consider AFM as a part of their research toolkit, by highlighting the manifold
      capabilities of this technique.

PMID- 22612783
TI  - Protein oxidative folding in the intermembrane mitochondrial space: more than
      protein trafficking.
AB  - The process of oxidative folding in the intermembrane mitochondrial space (IMS)
      is an exciting field of research because folding is simultaneously coupled to
      protein translocation and functional regulation. Contrary to the endoplasmatic
      reticulum ER where several chaperones of the disulfide isomerase family exist,
      oxidative folding in the IMS is exclusively catalyzed by the oxoreductase Mia40
      that recognizes a group of proteins with characteristic cysteine motifs organized
      in twin CX(3)C, twin CX(9)C or CX(2)C motifs. In this review, we discuss the
      structural and biochemical studies leading to our current understanding of the
      Mia40 pathway as well as the open questions on the field. In fact, despite
      significant advances, several key points on the Mia40 pathway remain to clarify
      namely on the molecular mechanism trough which substrate oxidative folding is
      catalyzed. This issue is receiving increasing attention since failures in the
      import, sorting and folding of mitochondrial proteins is related to an increasing
      number of debilitating human disorders.

PMID- 22612784
TI  - 5-HT2A receptor -1438 G/A polymorphism and serotonergic antidepressant-induced
      sexual dysfunction in male patients with major depressive disorder: a prospective
      exploratory study.
AB  - INTRODUCTION: To date, few studies have specifically investigated the genetic
      determinants of antidepressant-induced sexual dysfunction (SD). AIM: The aim of
      this prospective study was to examine whether the 5-HT2A receptor -1438 G/A
      polymorphism has functional consequences on sexual well-being in young adult men
      presenting with their first episode of major depressive disorder (MDD) after
      serotonergic antidepressant treatment. METHODS: Between May 2010 and June 2011, a
      total of 56 drug-naive patients presenting with their first episode of MDD were
      recruited from a psychiatric hospital and received either a selective serotonin
      reuptake inhibitor or venlafaxine monotherapy; the patients were then genotyped.
      Over the course of antidepressant treatment, the population was divided into a SD
      group (N=16) and a non-SD group (N=29) based on the Arizona Sexual Experience
      Scale (ASEX). Participants who did not achieve a significant improvement, as
      assessed by the Hamilton Depression Rating Scale (HAMD-17), were excluded from
      the final data analysis. MAIN OUTCOME MEASURES: The primary outcome measures were
      the differences in the genotype distribution and allele frequencies between
      groups. RESULTS: In the SD group, the AA genotype was significantly
      overrepresented (P=0.004), and the mean baseline HAMD-17 score, the mean baseline
      ASEX score, and the mean end-point ASEX score were significantly higher than
      those in the non-SD group (P=0.026, P=0.004, and P<0.001, respectively). The mean
      end-point HAMD-17 score (P=0.115) did not differ significantly between the two
      groups. CONCLUSION: These results suggest that the AA genotype may be a genetic
      trait offering an opportunity to strengthen early detection of serotonergic
      antidepressant-induced SD in young adult male patients with MDD, whereas the G
      allele is protective against SD in this population.

PMID- 22612785
TI  - Ultrasonographic and hysteroscopic outcomes of uterine scar healing after
      cesarean section: comparison of two types of single-layer suture.
AB  - AIM:  A common anatomical consequence of low-segment cesarean section is the
      presence of a pouch on the anterior uterine wall that can be detected by
      sonography or hysteroscopy. Different suturing techniques have been compared
      (single vs double layer) and showed no substantial differences. This prospective
      longitudinal study was aimed at evaluating the outcome of the cesarean scar,
      comparing two different types of single-layer sutures by transvaginal ultrasound
      and hysteroscopy. MATERIAL AND METHODS: The study sample consisted of two groups
      of 30 singleton primiparae at term who delivered by elective low segment cesarean
      section. In the first group, uterine closure was done with locked continuous
      single-layer sutures and in the second group, with single-layer interrupted
      sutures. Patients were assessed by transvaginal ultrasound and hysteroscopy,
      between the 6th and the 12th month after delivery, and again at the 24th month.
      Ultrasound measurements were made of the pouch area, if present. RESULTS: A bell
      shaped uterine wall defect was seen at ultrasound in 36 (85.71%) of 42 patients
      who completed the follow up at the 24th month. It was larger in the group of
      patients with closure by continuous sutures (6.2 [2.1-14.7] mm2) as compared to
      interrupted sutures (4.6 [1.9-8.2] mm2, P = 0.03). Hysteroscopy confirmed the
      presence of the wall defect in all 36 cases, but different hysteroscopic outcomes
      were observed. CONCLUSION: Locked continuous sutures seem to cause a larger
      defect as compared to interrupted sutures, probably due to a greater ischemic
      effect exerted on the uterine tissue.

PMID- 22612786
TI  - The congress kit: a futile waste of money.

PMID- 22612787
TI  - Computer-based assistive technology device for use by children with physical
      disabilities: a cross-sectional study.
AB  - OBJECTIVE: To investigate the prevalence of children with physical disabilities
      who used a computer-based ATD, and to examine characteristics differences in
      children and youths who do or do not use computer-based ATDs, as well as,
      investigate differences that might influence the satisfaction of those two groups
      of children and youths when computers are being used for in-school and outside
      school activities. METHOD: A cross-sectional survey about computer-based
      activities in and outside school (n = 287) and group comparisons. RESULTS: The
      prevalence of using computer-based ATDs was about 44 % (n = 127) of the children
      in this sample. These children were less satisfied with their computer use in
      education and outside school activities than the children who did not use an ATD.
      CONCLUSION: Improved coordination of the usage of computer-based ATDs in school
      and in the home, including service and support, could increase the opportunities
      for children with physical disabilities who use computer-based ATDs to perform
      the computer activities they want, need and are expected to do in school and
      outside school.

PMID- 22612788
TI  - Immune stimulating and therapeutic potential of tuftsin-incorporated nystatin
      liposomes against Cryptococcus neoformans in leukopenic BALB/C mice.
AB  - Cryptococcus neoformans infection is a common fungal infection in persons
      infected with human immune deficiency virus (HIV) or those with defective cell
      mediated immunity. Since treatment of cryptococcal meningitis poses a big
      challenge, the present study aimed to develop a novel liposomal therapeutic
      formulation against cryptococcosis. Treatment with tuftsin-incorporated liposomes
      increased the anti-cryptococcal activity of murine peritoneal macrophages.
      Prophylactic treatment of mice with tuftsin-incorporated liposomes reduced the
      dissemination of C. neoformans to brain tissues. Moreover, the co-administration
      of tuftsin with nystatin liposomes augmented the anti-cryptococcal activity of
      nystatin, as mice treated with tuftsin-incorporated nystatin liposomes showed the
      highest survival and least fungal burden in their brain tissues. The results of
      the present study favour the use of immune-stimulating molecules along with
      antifungal agents in the treatment of opportunistic fungal infections.

PMID- 22612789
TI  - A review of a paediatric emergency department vaccination programme for patients
      at risk of allergy/anaphylaxis.
AB  - AIM: We sought to review the clinical outcomes of patients referred to our
      emergency department (ED) vaccination service for children with a history of
      allergy or anaphylaxis or in whom there was a concern of a significant adverse
      reaction. METHODS: This was a prospective observational cohort study set in an
      urban tertiary Paediatric ED. All attendances for any childhood vaccination for a
      5-year period (from January 1, 2006 to December 31, 2010) were included. Our
      primary outcome measure was any adverse reaction as a result of the vaccine
      administered. RESULTS: A total of 446 vaccines were administered during the study
      period in 374 patients. Of these vaccinations, 310 (69.5%) were Measles, Mumps,
      Rubella (MMR). The majority of patients (348, 93%) were referred from the
      community. Suspected egg allergy was the reason for the majority of referrals for
      MMR (261/310 (84.2%)). Only six patients (1.3%) experienced an immediate reaction
      to a vaccination. All reactions were minor. CONCLUSION: This is one of the
      largest studies looking at childhood vaccinations performed in a hospital setting
      for children who are 'at risk' of allergy, anaphylaxis or hypersensitivity. A
      significant number of referrals were unwarranted and the majority could have been
      safely managed in the community.

PMID- 22612790
TI  - Impact of fresh and saline water flooding on leaf gas exchange in two Italian
      provenances of Tamarix africana Poiret.
AB  - In Mediterranean coastal areas, changes in precipitation patterns and seawater
      levels are leading to increased frequency of flooding and to salinization of
      estuaries and freshwater systems. Tamarix spp. are often the only woody species
      growing in such environments. These species are known for their tolerance to
      moderate salinity; however, contrasting information exists regarding their
      tolerance to flooding, and the combination of the two stresses has never been
      studied in Tamarix spp. Here, we analyse the photosynthetic responses of T.
      africana Poiret to temporary flooding (45 days) with fresh or saline water (200
      mm) in two Italian provenances (Simeto and Baratz). The measurements were
      conducted before and after the onset of flooding, to test the possible cumulative
      effects of the treatments and effects on twig aging, and to analyse the responses
      of twigs formed during the experimental period. Full tolerance was evident in T.
      africana with respect to flooding with fresh water, which did not affect
      photosynthetic performances in either provenance. Saline flooding was differently
      tolerated by the two provenances. Moreover, salinity tolerance differently
      affected the two twig generations. In particular, a reduction in net assimilation
      rate (-48.8%) was only observed in Baratz twigs formed during the experimental
      period, compared to pre-existing twigs. This reduction was a consequence of non
      stomatal limitations (maximum carboxylation rate and electron transport),
      probably as a result of higher Na transport to the twigs, coupled with reduced Na
      storage in the roots.

PMID- 22612791
TI  - Flexible cystoscopy findings in patients investigated for profound lower urinary
      tract symptoms, recurrent urinary tract infection, and pain.
AB  - BACKGROUND AND PURPOSE: The National Institute of Clinical Excellence published
      guidelines in 2010 recommending the use of cystoscopy to investigate profound
      lower urinary tract symptoms (pLUTS), recurrent urinary tract infection (rUTI),
      and pain in men. Currently, there are no equivalent guidelines for women. We
      aimed to examine the diagnostic performance of flexible cystoscopy (FC) when it
      is used in this context in both men and women. PATIENTS AND METHODS: Results of
      all outpatient FCs undertaken in our department between April 2009 and March 2010
      were examined retrospectively. Patients undergoing FC for the investigation of
      pLUTS, rUTI, or pain were included. Diagnostic performance was calculated, which
      was defined as the number of patients receiving a diagnosis of a clinically
      relevant abnormality at FC divided by the total number of patients undergoing FC
      for this indication. RESULTS: Of the 1809 patients who underwent FC during the
      study period, 113 underwent FC to investigate pLUTS, rUTI, or pain. Diagnostic
      performance was 11.5% (n=13), being 11.4%, 19.2%, and 0% in those with pLUTS,
      rUTI, and pain, respectively. Bladder cancer was diagnosed in one (0.9%) patient
      who underwent FC to investigate pLUTS but also had nonvisible hematuria. Urethral
      stricture was diagnosed in nine (8.0%) cases and intravesical calculi in four
      (3.5%) cases. CONCLUSION: Clinically relevant abnormalities were found in 11.5%
      of patients with pLUTS, rUTI, or pain, supporting recently published NICE
      guidelines recommending cystoscopy in patients with pLUTS or rUTI. Of the 17
      patients who were investigated for pain, none was found to have clinically
      relevant abnormalities; further studies are needed to define the clinical utility
      of FC in these cases.

PMID- 22612792
TI  - Elevated circulating tissue factor procoagulant activity, factor VII, and
      plasminogen activator inhibitor-1 in childhood obesity: evidence of a
      procoagulant state.
AB  - Childhood obesity is rapidly increasing in prevalence. We compared circulating
      membrane-bound tissue factor (FIII, F3) procoagulant activity (TF-PCA) and plasma
      markers of coagulation, fibrinolysis and endothelial dysfunction in 21 obese
      (10.1 +/- 1.5 years, mean +/- standard deviation) and 22 healthy weight children
      (9.9 +/- 1.6 years), classified by Body Mass Index (BMI). TF-PCA and factor VII
      coagulant activity (FVII:C), plasminogen activator inhibitor (PAI-1, SERPINE1)
      and soluble vascular cell adhesion molecule 1 (sVCAM1) were higher in obese
      children. BMI correlated positively with TF-PCA, FVII:C, and PAI-1. Childhood
      obesity is associated with a procoagulant state and endothelial dysfunction.
      Studies are needed to assess whether weight reduction reverses these
      abnormalities.

PMID- 22612793
TI  - Electronic information exchange between emergency departments and poison control
      centers: a Delphi study.
AB  - CONTEXT: The US emergency departments and poison control centers use telephone
      communication to exchange information about poison exposed patients.
      Electronically exchanged patient information could better support care for
      poisoned patients by improving information availability for decision making and
      by decreasing unnecessary emergency department telephone interruptions. As
      federal initiatives push to increase clinical health information exchange (HIE),
      it is essential to assess the readiness of US poison control centers. We
      conducted a nationwide Delphi study to determine consensus on legal, operational,
      and clinical considerations that are important for electronic information
      exchange between emergency departments and poison control centers. MATERIALS AND
      METHODS: A national panel of US experts (n = 71) in emergency medicine and poison
      control participated in a Delphi study, September-December 2010. Panelists rated
      statements describing concepts related to implementation, adoption, or potential
      outcomes of electronic information exchange between emergency departments and
      poison control centers. The statements reflected panelist responses to initial
      open-ended questions and literature-based concepts. RESULTS: A total of 71
      panelists agreed to participate. The response rate for each round ranged from
      0.73 to 0.77. Most (114/121) statements reached consensus. Seven statements
      failed to reach consensus. Panelists indicated that user involvement in the
      design of systems and tools is important. Workflow integration, safety, evidence
      of benefit, and outcomes are high-importance issues. DISCUSSION/CONCLUSIONS:
      Future research and development related to electronic information exchange should
      address high-importance issues: safety, patient outcomes, workflow integration,
      and evidence of benefit. It should also address key barriers: initial and ongoing
      costs associated with electronic information exchange, the absence of software
      and tools to facilitate exchange, and the need for training. Users should be
      involved in the design of an electronic information exchange process, and the
      process should support, not replace, verbal communication.

PMID- 22612794
TI  - Imatinib-induced liver cirrhosis in a patient with advanced gastrointestinal
      stroma tumor (GIST).
AB  - BACKGROUND: The use of imatinib mesylate is associated with a progression free
      survival of 41 months in first line treatment of metastatic or locally advanced
      gastrointestinal stromal tumors (GIST) and other studies approved that adjuvant
      imatinib treatment improves the recurrence-free survival in patients with GIST.
      Current recommendations include 1 year adjuvant treatment in GIST patients at
      risk but active studies explore different durations of treatment with an interval
      of up to 5 years. While the most frequent adverse events (AEs) are blood count
      alterations, abdominal discomfort and edema, the occurrence of grade 3 or 4
      increase of AST or ALT is specified with 2.1% and 2.7% respectively. CASE
      PRESENTATION: We report a 49-year old male with a gastrointestinal stromal tumor
      (GIST) of the small bowel who developed liver cirrhosis under adjuvant imatinib
      treatment. CONCLUSIONS: Our report supports the notion that imatinib-induced
      hepatotoxicity may lead to acute liver damage with subsequent cirrhotic
      remodelling. Patients developing grade 3 or 4 hepatotoxicity during imatinib
      treatment should therefore be carefully evaluated for chronic liver disease.

PMID- 22612795
TI  - Cardiac medical conditions have become the leading cause of death in children
      with heart disease.
AB  - OBJECTIVE: Mortality among children with congenital and acquired heart disease
      has decreased significantly over the past decades. We sought to determine whether
      the underlying problems leading to death in these patients had changed over the
      past decade. METHODS: We reviewed medical records for 100 deaths of cardiac
      patients in 2004-2005 and 100 deaths in 1995-1996. Demographic, clinical, and
      procedural data as well as circumstances of death were collected. A consensus
      committee reviewed each case and sought to identify the condition leading to
      death. These conditions were classified as predominantly surgical or medical.
      RESULTS: General patient characteristics (age, gender, cardiac history,
      comorbidities, proportion of surgical patients) did not change significantly
      between the two time periods. However, in 1995-1996, 64% of deceased surgical
      patients had died within 30 days of surgery. This rate was nearly halved to only
      38% by 2004-2005 (P= .003). Furthermore, the conditions leading to death changed
      significantly: 51% of patient deaths in 1995-1996 resulted from a surgical
      problem, 29% from a medical condition. This ratio was reversed in 2004-2005: Only
      31% of patient deaths were due to a surgical problem, while 50% of deaths
      resulted from a medical condition (P= .005). The most common medical conditions
      resulting in death were pulmonary vein stenosis, pulmonary arterial hypertension,
      and primary myocardial failure. CONCLUSIONS: The proportion of deaths within 30
      days of cardiac surgery decreased significantly over the past decade. While
      surgical causes accounted for the majority of these deaths in 1995-1996, most
      patient deaths in 2004-2005 resulted from cardiac medical causes.

PMID- 22612796
TI  - Post-infarct biomaterials, left ventricular remodeling, and heart failure: is
      good good enough?

PMID- 22612800
TI  - Seventh Conversation in the Discipline Biomolecular Stereodynamics State
      University of New York at Albany, June 18-22, 1991.

PMID- 22612802
TI  - The neuroanatomist--a tribute to H. Jurgen Wenzel.

PMID- 22612797
TI  - Clinical utility of a novel colorimetric chair side test for oral malodour.
AB  - AIM: The aim of this study was to evaluate the utility of a simple colorimetric
      chair side test detecting amines in saliva as an adjunct test in the oral
      malodour diagnosis. MATERIAL AND METHODS: Non-stimulated saliva samples were
      collected from 100 volunteers with different degrees of oral malodour. The amount
      of amines detected by the test was estimated clinically (colorimetric test),
      confirmed semi quantitatively in the laboratory (standard addition method) and
      consequently compared with (i) the organoleptic score (OLS); (ii) the volatile
      sulphur compounds (VSCs) levels (OralChroma(TM)) and (iii) the amount of amines
      detected by means of gas chromatography - mass spectroscopy. RESULTS: The chair
      side test correlated well (Spearman correlation coefficient: 0.46-0.77), with the
      OLS, the level of VSCs, and the amines determined by using gas chromatography -
      mass spectroscopy. The results of the new test for patients with and without oral
      malodour were significantly different (Mann-Whitney U-test, p < 0.0001). The
      sensitivity, specificity, and positive and negative predictive value of this
      chair side test were similar to those of the VSCs evaluations. CONCLUSIONS: These
      results support the "fit for purpose" of the new chair side test as adjunctive
      diagnostic tool for oral malodour.

PMID- 22612803
TI  - Fine structure of hippocampal mossy fiber synapses following rapid high-pressure
      freezing.
AB  - Synapses of hippocampal neurons play important roles in learning and memory
      processes and are involved in aberrant hippocampal function in temporal lobe
      epilepsy. Major neuronal types in the hippocampus as well as their input and
      output synapses are well known, but it has remained an open question to what
      extent conventional electron microscopy (EM) has provided us with the real
      appearance of synaptic fine structure under in vivo conditions. There is reason
      to assume that conventional aldehyde fixation and dehydration lead to protein
      denaturation and tissue shrinkage, likely associated with the occurrence of
      artifacts. However, realistic fine-structural data of synapses are required for
      our understanding of the transmission process and for its simulation. Here, we
      used high-pressure freezing and cryosubstitution of hippocampal tissue that was
      not subjected to aldehyde fixation and dehydration in ethanol to monitor the fine
      structure of an identified synapse in the hippocampal CA3 region, that is, the
      synapse between granule cell axons, the mossy fibers, and the proximal dendrites
      of CA3 pyramidal neurons. Our results showed that high-pressure freezing nicely
      preserved ultrastructural detail of this particular synapse and allowed us to
      study rapid structural changes associated with synaptic plasticity.

PMID- 22612804
TI  - Mossy cell dendritic structure quantified and compared with other hippocampal
      neurons labeled in rats in vivo.
AB  - Mossy cells are likely to contribute to normal hippocampal function and to the
      pathogenesis of neurologic disorders that involve the hippocampus, including
      epilepsy. Mossy cells are the least well-characterized excitatory neurons in the
      hippocampus. Their somatic and dendritic morphology has been described
      qualitatively but not quantitatively. In the present study rat mossy cells were
      labeled intracellularly with biocytin in vivo. Somatic and dendritic structure
      was reconstructed three-dimensionally. For comparison, granule cells, CA3
      pyramidal cells, and CA1 pyramidal cells were labeled and analyzed using the same
      approach. Among the four types of hippocampal neurons, granule cells had the
      smallest somata, fewest primary dendrites and dendritic branches, and shortest
      total dendritic length. CA1 pyramidal cells had the most dendritic branches and
      longest total dendritic length. Mossy cells and CA3 pyramidal cells both had
      large somata and similar total dendritic lengths. However, mossy cell dendrites
      branched less than CA3 pyramidal cells, especially close to the soma. These
      findings suggest that mossy cells have dendritic features that are not identical
      to any other type of hippocampal neuron. Therefore, electrotonic properties that
      depend on soma-dendritic structure are likely to be distinct in mossy cells
      compared to other neurons.

PMID- 22612805
TI  - The extracellular space and epileptic activity in the adult brain: explaining the
      antiepileptic effects of furosemide and bumetanide.
AB  - Treatments that modulate the size of the extracellular space (ECS) also block
      epileptiform activity in adult brain tissue. This includes the loop diuretics
      furosemide and bumetanide, and alterations of the osmolarity of the ECS. These
      treatments block epileptiform activity in a variety of laboratory adult seizure
      models regardless of the underlying synaptic and physiologic mechanisms
      generating the seizure activity. Optical imaging studies on adult hippocampal
      slices show that the blockade of epileptiform activity by these treatments is
      concomitant with their blockade of activity-driven changes of the ECS. Here we
      develop and analyze the hypothesis that activity-driven changes in the size of
      the ECS are necessary for the maintenance of hypersynchronous epileptiform
      activity. In support of this hypothesis is an accumulation of data from a number
      of studies suggesting that furosemide and bumetanide mediate antiepileptic
      effects through their blockade of cell swelling, dependent on their antagonism of
      the glial Na+-K-2Cl cotransporter (NKCC1).

PMID- 22612807
TI  - Are developmental dysplastic lesions epileptogenic?
AB  - Cortical dysplasia of various types, reflecting abnormalities of brain
      development, have been closely associated with epileptic activities. Yet, there
      remains considerable discussion about if/how these structural lesions give rise
      to seizure phenomenology. Animal models have been used to investigate the cause
      effect relationships between aberrant cortical structure and epilepsy. In this
      article, we discuss three such models: (1) the Eker rat model of tuberous
      sclerosis, in which a gene mutation gives rise to cortical disorganization and
      cytologically abnormal cellular elements; (2) the p35 knockout mouse, in which
      the genetic dysfunction gives rise to compromised cortical organization and
      lamination, but in which the cellular elements appear normal; and (3) the
      methylazoxymethanol-exposed rat, in which time-specific chemical DNA disruption
      leads to abnormal patterns of cell formation and migration, resulting in
      heterotopic neuronal clusters. Integrating data from studies of these animal
      models with related clinical observations, we propose that the neuropathologic
      features of these cortical dysplastic lesions are insufficient to determine the
      seizure-initiating process. Rather, it is their interaction with a more subtly
      disrupted cortical "surround" that constitutes the circuitry underlying
      epileptiform activities as well as seizure propensity and ictogenesis.

PMID- 22612806
TI  - Are you in or out? Leukocyte, ion, and neurotransmitter permeability across the
      epileptic blood-brain barrier.
AB  - The credo that epileptic seizures can be initiated only by "epileptic" neurons
      has been recently challenged. The recognition of key astrocytic-neuronal
      communication, and the close interaction and crosstalk between astrocytes and
      brain endothelial cells, has shifted attention to the blood-brain barrier (BBB)
      and the "neurovascular unit." Therefore, the pursuit of mechanisms of seizure
      generation and epileptogenesis now includes investigations of cerebral blood flow
      and permeability of cerebral microvessels. For example, leukocyte adhesion
      molecules at the BBB have been proposed to play a role as an initiating factor
      for pilocarpine-induced status epilepticus, and a viral infection model with a
      strong BBB etiology has been used to study epileptogenesis. Finally, the fact
      that in nonepileptic subjects seizures can be triggered by BBB disruption,
      together with the antiseizure effects obtained by administration of potent
      antiinflammatory "BBB repair" drugs, has increased the interest in
      neuroinflammation; both circulating leukocytes and resident microglia have been
      studied in this context. The dual scope of this review is the following: (1)
      outline the proposed role of BBB damage and immune cell activation in seizure
      disorders; and (2) explain how increased cerebrovascular permeability causes
      neuronal misfiring. The temporal sequence linking seizures to peripheral
      inflammation and BBB dysfunction remains to be clarified. For example, it is
      still debated whether seizures cause systemic inflammation or vice versa. The
      topographic localization of fundamental triggers of epileptic seizures also
      remains controversial: Are immunologic mechanisms required for seizure generation
      brain-specific or is systemic activation of immunity sufficient to alter neuronal
      excitability? Finally, the causative role of "BBB leakage" remains a largely
      unresolved issue.

PMID- 22612808
TI  - Neuronal excitability and calcium/calmodulin-dependent protein kinase type II:
      location, location, location.
AB  - Calcium/calmodulin-dependent protein kinase type II (CaMKII) is a highly abundant
      serine/threonine kinase comprising a significant fraction of total protein in
      mammalian forebrain and forming a major component of the postsynaptic density.
      CaMKII is essential for certain forms of synaptic plasticity and memory
      consolidation and this is mediated through substrate binding and intramolecular
      phosphorylation of holoenzyme subunits. CaMKII is multifunctional; it targets a
      variety of cellular substrates, and this diversity depends on holoenzyme subunit
      composition. CaMKII comprises homooligomeric and heterooligomeric complexes
      generated from four subunits (alpha, beta, delta, and gamma) encoded by separate
      genes that are further expanded by extensive alternative splicing to more than 30
      different isoforms. Much attention has been paid to understanding the regulation
      of CaMKII function through its structural diversity and/or substrate specificity.
      However, given the importance of subunit composition to holoenzyme activity, it
      is likely that specificity of cellular expression of CaMKII isoforms also plays a
      major role in regulation of enzyme function. Herein we review the cellular
      colocalization of CaMKII isoforms with special regard to the cell-type
      specificity of isoform expression in brain. In addition, we highlight the
      remarkable specificity of subcellular localization by the CaMKIIalpha isoform. In
      addition, we discuss the role that this cellular specificity of expression might
      play in propagating the type of recurrent neuronal activity associated with
      disorders such as temporal lobe epilepsy.

PMID- 22612809
TI  - In vitro mechanical strain trauma alters neuronal calcium responses: Implications
      for posttraumatic epilepsy.
AB  - Traumatic brain injury (TBI) is known to initiate a series of chemical cascades
      resulting in neuronal dysfunction and death. Epidemiology studies have found that
      a prior incidence of TBI is the most important cause of remote symptomatic
      epilepsy in young adults and children. TBI-induced changes in neuronal
      sensitivity to stimulation may contribute to acute seizures and the eventual
      generation of epilepsy. This study examined TBI-induced changes in neuronal
      sensitivity to stimulation by measuring intracellular calcium ([Ca(++) ](i) )
      responses in neurons during glutamate application in vitro. Initial experiments
      examined neuronal and glial cell death and determined that a 31% mechanical
      strain trauma to mixed neuronal-astrocyte rat cortical cultures produced a trend,
      but no significant cell death at 48 h after injury. Subsequent experiments
      utilized this magnitude of trauma to examine the sensitivity of cortical neurons
      to changes in [Ca(++) ](i)  in response to 100-MUm glutamate at five time points
      postinjury (1, 6, 24, 48, and 72 h). Traumatically strain-injured neurons
      responded with a dynamic change in the accumulation of [Ca(++) ](i) , with a
      significant increase at 48 h and a significant decrease at 72 h as compared to
      uninjured cultures. These data highlight that TBI leads to abnormal
      responsiveness to stimulation, an indicator of neuronal dysfunction in surviving
      cells. Such changes in sensitivity to stimulation may also be associated with
      changes in excitability in the first hours to days after TBI, and may play a role
      in early posttraumatic seizures observed in patients with TBI. In addition, this
      study provides an in vitro paradigm for testing the function of surviving cells
      following treatment interventions targeted at reducing cell death and
      dysfunction.

PMID- 22612810
TI  - Common factors among Alzheimer's disease, Parkinson's disease, and epilepsy:
      possible role of the noradrenergic nervous system.
AB  - The neurodegenerative disorders Alzheimer's disease (AD) and Parkinson's disease
      (PD) share in common the neuropathologic loss of locus coeruleus (LC)
      noradrenergic neurons. In addition, these two neurodegenerative disorders share
      two symptoms that define these disorders: cognitive impairment and depression.
      The hippocampus is a region that is known to play a role in cognition and
      depression, and the hippocampus receives sole noradrenergic innervation from LC
      neurons. However, it is unclear how the loss of LC noradrenergic neurons
      contributes to these common symptoms in these two disorders. Epilepsy is not
      considered a neurodegenerative disorder, but the hippocampus is severely affected
      in temporal lobe epilepsy. Of interest, cognitive impairment and depression are
      also common comorbid disorders in temporal lobe epilepsy. This article describes
      common symptoms among these three neurologic disorders and a possible role of the
      noradrenergic nervous system.

PMID- 22612812
TI  - The mTOR pathway is activated in glial cells in mesial temporal sclerosis.
AB  - Mammalian target of rapamycin (mTOR) is a key protein kinase that regulates basic
      cellular processes, including development and growth. Mutations in mTOR cause
      tuberous sclerosis complex (TSC), a condition that is characterized by
      developmental brain malformations (cortical tubers) and epilepsy. Although
      considerable insight has been gained recently into the pathologic dysfunction of
      mTOR in tubers in TSC-related epilepsy, data on the mTOR cascade in mesial
      temporal lobe epilepsy (MTLE) are lacking. Immunohistochemical investigation with
      confocal microscopy was performed to evaluate mTOR cascade and to correlate its
      activity with cellular alterations observed in surgically resected samples of
      human neocortex and hippocampus in MTLE. We compared results in human tissue to
      findings in the rat pilocarpine model of sclerotic MTLE. In nonsclerotic and
      control hippocampus, many neurons in the CA1 subfield expressed high levels of
      phospho-S6 (p-S6), a reliable marker of mTOR activation. In nonsclerotic and
      control hippocampus, as well as in magnetic resonance imaging (MRI) normal human
      neocortex, protoplasmic astrocytes did not express p-S6. In contrast, in
      sclerotic hippocampus, prominent p-S6 immunostaining was observed mainly in
      astrocytes and microglia located in the areas of neuronal loss and astrogliosis,
      whereas neurons in preserved areas of CA1 expressed significantly lower levels of
      p-S6 immunopositivity than neurons in nonsclerotic or control CA1 subfields. In
      surgically resected neocortex with chronic astroglial scar tissue, only microglia
      revealed moderate p-S6 immunoreactivity. Different from human sclerotic epileptic
      hippocampus, astrogliosis in the chronic rat pilocarpine model of epilepsy was
      not characterized by glial cells with mTOR activation. The mTOR cascade is
      activated in astroglial cells in sclerotic MTLE, but not in astrocytes in chronic
      neocortical scarring or in the pilocarpine model of MTLE. These findings suggest
      that the astroglial "scar" in sclerotic MTLE has active, ongoing cellular
      changes. Targeting mTOR in MTLE may provide new pathways for the medical therapy
      of epilepsy.

PMID- 22612811
TI  - Neuroanatomical clues to altered neuronal activity in epilepsy: from
      ultrastructure to signaling pathways of dentate granule cells.
AB  - The dynamic aspects of epilepsy, in which seizures occur sporadically and are
      interspersed with periods of relatively normal brain function, present special
      challenges for neuroanatomical studies. Although numerous morphologic changes can
      be identified during the chronic period, the relationship of many of these
      changes to seizure generation and propagation remains unclear. Mossy fiber
      sprouting is an example of a frequently observed morphologic change for which a
      functional role in epilepsy continues to be debated. This review focuses on
      neuroanatomically identified changes that would support high levels of activity
      in reorganized mossy fibers and potentially associated granule cell activation.
      Early ultrastructural studies of reorganized mossy fiber terminals in human
      temporal lobe epilepsy tissue have identified morphologic substrates for highly
      efficacious excitatory connections among granule cells. If similar connections in
      animal models contribute to seizure activity, activation of granule cells would
      be expected. Increased labeling with two activity-related markers, Fos and
      phosphorylated extracellular signal-regulated kinase, has suggested increased
      activity of dentate granule cells at the time of spontaneous seizures in a mouse
      model of epilepsy. However, neuroanatomical support for a direct link between
      activation of reorganized mossy fiber terminals and increased granule cell
      activity remains elusive. As novel activity-related markers are developed, it may
      yet be possible to demonstrate such functional links and allow mapping of seizure
      activity throughout the brain. Relating patterns of neuronal activity during
      seizures to the underlying morphologic changes could provide important new
      insights into the basic mechanisms of epilepsy and seizure generation.

PMID- 22612813
TI  - Optical imaging of visual cortex epileptic foci and propagation pathways.
AB  - Precise localization of neocortical epileptic foci is a complex problem that
      usually requires ictal video-electroencephalography (EEG) recordings; high
      resolution magnetic resonance imaging (MRI), positron emission tomography (PET),
      and single photon emission computed tomography (SPECT) studies; and/or invasive
      monitoring with implanted grid array electrodes. The exact ictal-onset site must
      be identified and removed to obtain the best opportunity for a seizure-free
      outcome. The goal of this study was to determine if high-resolution optical
      imaging could precisely identify neocortical epileptic foci and what role
      underlying neuroanatomic pathways played in the seizure propagation. Small acute
      epileptic foci (0.5 * 0.5 mm(2) ) were created in the primate visual neocortex
      and single-unit and surface EEG recordings were combined with optical imaging of
      voltage-sensitive dye changes. Brief visual stimulation was used to evoke
      interictal bursts. In addition, different visually evoked epileptiform bursts
      were analyzed to determine the location of the epileptic focus. Spike-triggered
      averaging of the optical images associated with the surface EEG interictal bursts
      were analyzed to determine the exact location of the epileptic focus. Specific
      orientations of brief visual stimulation evoked different intensity optical
      changes and precisely localized the epileptic focus. Optical imaging identified
      individual epileptic foci that were <3 mm apart. The development of individual
      epileptic focus was monitored with optical imaging, which demonstrated excitatory
      activity at the focus with a surrounding zone of inhibitory-like activity.
      Propagation pathways outside of the inhibitory-like surround demonstrated
      alternating bands of excitation and inhibition with a pattern orthogonal to the
      ocular dominance columns. This experimental study demonstrates that optical
      imaging can precisely localize an epileptic focus, and provides excellent spatial
      resolution of the changes that occur in and around the site of the epileptic
      focus.

PMID- 22612814
TI  - Synaptic connections of hilar basal dendrites of dentate granule cells in a
      neonatal hypoxia model of epilepsy.
AB  - Numerous animal models of epileptogenesis demonstrate neuroplastic changes in the
      hippocampus. These changes occur not only for the mature neurons and glia, but
      also for the newly generated granule cells in the dentate gyrus. One of these
      changes, the sprouting of mossy fiber axons, is derived predominantly from
      newborn granule cells in adult rats with pilocarpine-induced temporal lobe
      epilepsy. Newborn granule cells also mainly contribute to another neuroplastic
      change, hilar basal dendrites (HBDs), which are synaptically targeted by mossy
      fibers in the hilus. Both sprouted mossy fibers and HBDs contribute to recurrent
      excitatory circuitry that is hypothesized to be involved in increased seizure
      susceptibility and the development of spontaneous recurrent seizures (SRS) that
      occur following the initial pilocarpine-induced status epilepticus. Considering
      the putative role of these neuroplastic changes in epileptogenesis, a critical
      question is whether similar anatomic phenomena occur after epileptogenic insults
      to the immature brain, where the proportion of recently born granule cells is
      higher due to ongoing maturation. The current study aimed to determine if such
      neuroplastic changes could be observed in a standardized model of neonatal
      seizure-inducing hypoxia that results in development of SRS. We used
      immunoelectron microscopy for the immature neuronal marker doublecortin to label
      newborn neurons and their HBDs following neonatal hypoxia. Our goal was to
      determine whether synapses form on HBDs from neurons born after neonatal hypoxia.
      Our results show a robust synapse formation on HBDs from animals that experienced
      neonatal hypoxia, regardless of whether the animals experienced tonic-clonic
      seizures during the hypoxic event. In both cases, the axon terminals that synapse
      onto HBDs were identified as mossy fiber terminals, based on the appearance of
      dense core vesicles. No such synapses were observed on HBDs from newborn granule
      cells obtained from sham animals analyzed at the same time points. This aberrant
      circuit formation may provide an anatomic substrate for increased seizure
      susceptibility and the development of epilepsy.

PMID- 22612816
TI  - Impact of seizures on developing dendrites: implications for intellectual
      developmental disabilities.
AB  - Childhood epilepsy can be severe and even catastrophic. In these instances,
      cognition can be impaired-leading to long-term intellectual disabilities. One
      factor that could potentially cause cognitive deficits is the frequent seizures
      that characterize intractable epilepsy. However, it has been difficult to
      separate the effects seizures may have from those of preexisting neuropathologies
      and/or the effects of ongoing anticonvulsant therapies. Therefore, important
      questions are: Do early life seizures produce the learning deficits? And if they
      do, how do they do it? Results from recent animal models studies reviewed here
      show that recurrent seizures in infancy stop the growth of CA1 hippocampal
      dendrites. We speculate that the molecular mechanisms responsible for seizure
      induced growth suppression are homeostatic/neuroprotective, used by the
      developing nervous system in an attempt to limit neuronal and network
      excitability and prevent the continued generation of seizures. However, by
      preventing the normal growth of dendrites, there is a reduction in CA1
      glutamatergic synapses that supports long-lasting forms of synaptic plasticity
      thought to be the cellular basis of learning and memory. Therefore, dendrite
      growth suppression would reduce the neuroanatomic substrates for learning and
      memory, and in so doing could contribute in important ways to spatial learning
      and memory deficits that may be relevant to the cognitive deficits associated
      with childhood epilepsy.

PMID- 22612815
TI  - New insights into the role of hilar ectopic granule cells in the dentate gyrus
      based on quantitative anatomic analysis and three-dimensional reconstruction.
AB  - The dentate gyrus is one of two main areas of the mammalian brain where neurons
      are born throughout adulthood, a phenomenon called postnatal neurogenesis. Most
      of the neurons that are generated are granule cells (GCs), the major principal
      cell type in the dentate gyrus. Some adult-born granule cells develop in ectopic
      locations, such as the dentate hilus. The generation of hilar ectopic granule
      cells (HEGCs) is greatly increased in several animal models of epilepsy and has
      also been demonstrated in surgical specimens from patients with intractable
      temporal lobe epilepsy (TLE). Herein we review the results of our quantitative
      neuroanatomic analysis of HEGCs that were filled with Neurobiotin following
      electrophysiologic characterization in hippocampal slices. The data suggest that
      two types of HEGCs exist, based on a proximal or distal location of the cell body
      relative to the granule cell layer, and based on the location of most of the
      dendrites, in the molecular layer or hilus. Three-dimensional reconstruction
      revealed that the dendrites of distal HEGCs can extend along the transverse and
      longitudinal axis of the hippocampus. Analysis of axons demonstrated that HEGCs
      have projections that contribute to the normal mossy fiber innervation of CA3 as
      well as the abnormal sprouted fibers in the inner molecular layer of epileptic
      rodents (mossy fiber sprouting). These data support the idea that HEGCs could
      function as a "hub" cell in the dentate gyrus and play a critical role in network
      excitability.

PMID- 22612817
TI  - Acute, but reversible, kainic acid-induced DNA damage in hippocampal CA1
      pyramidal cells of p53-deficient mice.
AB  - p53 plays an essential role in mediating apoptotic responses to cellular stress,
      especially DNA damage. In a kainic acid (KA)-induced seizure model in mice,
      hippocampal CA1 pyramidal cells undergo delayed neuronal death at day 3-4
      following systemic KA administration. We previously demonstrated that CA1 neurons
      in p53(-/-)  animals are protected from such apoptotic neuronal loss. However,
      extensive morphological damage associated with DNA strand breaks in CA1 neurons
      was found in a fraction of p53(-/-)  animals at earlier time points (8 h to 2
      days). No comparable acute damage was observed in wild-type animals.
      Stereological counting confirmed that there was no significant loss of CA1
      pyramidal cells in p53(-/-)  animals at 7 days post-KA injection. These results
      suggest that seizure-induced DNA strand breaks are accumulated to a greater
      extent but do not lead to apoptosis in the absence of p53. In wild-type animals,
      therefore, p53 appears to stimulate DNA repair and also mediate apoptosis in CA1
      neurons in this excitotoxicity model. These results also reflect remarkable
      plasticity of neurons in recovery from injury.

PMID- 22612818
TI  - Kv1.1 and Kv1.2: similar channels, different seizure models.
AB  - Voltage-gated K(+)  channels (Kv) represent the largest family of genes in the
      K(+)  channel family. The Kv1 subfamily plays an essential role in the initiation
      and shaping of action potentials, influencing action potential firing patterns
      and controlling neuronal excitability. Overlapping patterns with differential
      expression and precise localization of Kv1.1 and Kv1.2 channels targeted to
      specialized subcellular compartments contribute to distinctive patterns of
      neuronal excitability. Dynamic regulation of the components in these subcellular
      domains help to finely tune the cellular and regional networks. Disruption of the
      expression, distribution, and density of these channels through deletion or
      mutation of the genes encoding these channels, Kcna1 and Kcna2, is associated
      with neurologic pathologies including epilepsy and ataxia in humans and in rodent
      models. Kv1.1 and Kv1.2 knockout mice both have seizures beginning early in
      development; however, each express a different seizure type (pathway), although
      the channels are from the same subfamily and are abundantly coexpressed. Voltage
      gated ion channels clustered in specific locations may present a novel
      therapeutic target for influencing excitability in neurologic disorders
      associated with some channelopathies.

PMID- 22612819
TI  - The importance of immunohistochemical analyses in evaluating the phenotype of Kv
      channel knockout mice.
AB  - To gain insights into the phenotype of voltage-gated potassium (Kv)1.1 and Kv4.2
      knockout mice, we used immunohistochemistry to analyze the expression of
      component principal or alpha subunits and auxiliary subunits of neuronal Kv
      channels in knockout mouse brains. Genetic ablation of the Kv1.1 alpha subunit
      did not result in compensatory changes in the expression levels or subcellular
      distribution of related ion channel subunits in hippocampal medial perforant path
      and mossy fiber nerve terminals, where high levels of Kv1.1 are normally
      expressed. Genetic ablation of the Kv4.2 alpha subunit did not result in altered
      neuronal cytoarchitecture of the hippocampus. Although Kv4.2 knockout mice did
      not exhibit compensatory changes in the expression levels or subcellular
      distribution of the related Kv4.3 alpha subunit, we found dramatic decreases in
      the cellular and subcellular expression of specific Kv channel interacting
      proteins (KChIPs) that reflected their degree of association and colocalization
      with Kv4.2 in wild-type mouse and rat brains. These studies highlight the
      insights that can be gained by performing detailed immunohistochemical analyses
      of Kv channel knockout mouse brains.

PMID- 22612821
TI  - Inhibition and interneuron distribution in the dentate gyrus of p35 knockout
      mice.
AB  - The p35 knockout (p35-/-) mouse is an animal model of temporal lobe epilepsy that
      recapitulates key neuroanatomic abnormalities-granule cell dispersion and mossy
      fiber sprouting-observed in the hippocampal formation of humans, as well as
      spontaneous seizure activity. It is a useful model in which to study the
      relationship between the abnormal neuronal structure and seizure activity to
      further our understanding of cortical dysplasia in epileptogenesis. Our previous
      work using this mouse model characterized the anatomic features of the dentate
      granule cells and the functional implications of these abnormalities on increased
      recurrent excitation. These data also suggested that there might be compromised
      inhibition in this animal model. We pursued this possibility, focusing our
      investigation on inhibitory circuitry. In preliminary investigations using
      neuroanatomic tools (immunocytochemistry, camera lucida reconstructions of
      individually labeled interneurons, and electron microscopy) combined with
      intracellular electrophysiology, we observed no significant reduction in the
      number of symmetric versus asymmetric synaptic contacts on dentate granule cell
      somata, and no statistically significant changes in evoked early or late
      inhibition. Although there were some abnormalities in the morphology/distribution
      of inhibitory interneurons (as well as a larger population of dentate granule
      cells) of the dentate gyrus, overall inhibition in the p35 knockout mouse
      appeared to be largely intact.

PMID- 22612822
TI  - Perishing misconduct!

PMID- 22612820
TI  - Abnormal dendrite and spine morphology in primary visual cortex in the CGG knock
      in mouse model of the fragile X premutation.
AB  - The fragile X mental retardation 1 gene (Fmr1) is polymorphic for CGG
      trinucleotide repeat number in the 5'-untranslated region, with repeat lengths
      <45 associated with typical development and repeat lengths >200 resulting in
      hypermethylation and transcriptional silencing of the gene and mental retardation
      in the fragile X Syndrome (FXS). Individuals with CGG repeat expansions between
      55 and 200 are carriers of the fragile X premutation (PM). PM carriers show a
      phenotype that can include anxiety, depression, social phobia, and memory
      deficits. They are also at risk for developing fragile X-associated tremor/ataxia
      syndrome (FXTAS), a late onset neurodegenerative disorder characterized by
      tremor, ataxia, cognitive impairment, and neuropathologic features including
      intranuclear inclusions in neurons and astrocytes, loss of Purkinje cells, and
      white matter disease. However, very little is known about dendritic morphology in
      PM or in FXTAS. Therefore, we carried out a Golgi study of dendritic complexity
      and dendritic spine morphology in layer II/III pyramidal neurons in primary
      visual cortex in a knock-in (KI) mouse model of the PM. These CGG KI mice carry
      an expanded CGG trinucleotide repeat on Fmr1, and model many features of the PM
      and FXTAS. Compared to wild-type (WT) mice, CGG KI mice showed fewer dendritic
      branches proximal to the soma, reduced total dendritic length, and a higher
      frequency of longer dendritic spines. The distribution of morphologic spine types
      (e.g., stubby, mushroom, filopodial) did not differ between WT and KI mice. These
      findings demonstrate that synaptic circuitry is abnormal in visual cortex of mice
      used to model the PM, and suggest that such changes may underlie neurologic
      features found in individuals carrying the PM as well as in individuals with
      FXTAS.

PMID- 22612823
TI  - Aetiology and therapeutics of burning mouth syndrome: an update.
AB  - OBJECTIVE: To provide a review on the aetiology and therapeutic options for the
      management of patients with burning mouth syndrome (BMS). BACKGROUND: BMS is a
      chronic disorder that frequently affects women and is characterised by burning
      symptoms of the oral mucosa without clinical signs. This syndrome has a complex
      and multifactorial characteristics, but its aetiology remains unknown and this
      makes it difficult with regard to the treatment and management of such patients.
      Despite not being accompanied by evident organic changes and not presenting risks
      to health, BMS can significantly reduce the quality of life for patients. METHODS
      AND MATERIALS: The article reviews the literature regarding aetiologic factors,
      clinical implications and treatment of BMS. CONCLUSION: involvement of
      neurological, emotional and hormonal alterations is proposed in BMS aetiology.
      However the mechanisms of its development are complex and not completely
      understood. Tricyclic antidepressants, benzodiazepines and antipsychotic drugs
      are the most accepted options in treatment and show variable results. The correct
      diagnosis of BMS and the exclusion of possible local or systemic factors that can
      be associated with the symptoms are fundamental. It is also important to evaluate
      the quality of life for these patients to recognise the potential impact of this
      condition on their lives.

PMID- 22612824
TI  - Pulp sensibility test in elderly patients.
AB  - BACKGROUND: The ageing process transforms the histological composition of the
      dental pulp and may affect the response to pulp sensibility tests. OBJECTIVES:
      The aim of this study was to assess the influence of age on pulp response time
      and on pain intensity. MATERIAL AND METHODS: Fifty elderly patients and 50 young
      patients were selected. Different classes of teeth were evaluated. The pulp
      sensibility test was performed with a refrigerant spray. The pulp response time
      was measured in seconds and the pain intensity was assessed by visual analogue
      scale. RESULTS: The Spearman coefficient was calculated and detect a positive
      correlation between age and pulp response time for maxillary incisors, premolars,
      mandibular incisors, and mean (p < 0.05). On the contrary, there was a negative
      correlation between age and pain intensity for maxillary incisors, mandibular
      incisors, and mean (p < 0.05). Also, the results of elderly and young groups were
      compared by Mann-Whitney test. Significant difference was noted regarding the
      pulp response time for maxillary incisors, premolars, mandibular incisors, and
      mean (p < 0.05). Significant difference was detected regarding the pain intensity
      for mandibular incisors only (p < 0.05). CONCLUSIONS: Pulp response time
      increases when people get older while pain intensity decreases. There were
      variations among the classes of teeth.

PMID- 22612825
TI  - Rehabilitation with ear prosthesis linked to osseointegrated implants.
AB  - BACKGROUND: The absence of an ear, which can be the result of a congenital
      malformation, surgical tumour resection or traumatic injury, is a significant
      aesthetic problem. Attachment of ear prostheses with adhesives can cause local
      irritation for the wearer and affect the colour of the prostheses. Use of
      implants in craniofacial reconstruction can improve the retention and stability
      of prostheses giving to patient greater comfort and security relative to adhesive
      attachment. OBJECTIVE: The aim of this report was to present a clinical case of a
      mutilated patient who was rehabilitated by means of installing an ear prosthesis
      fixed through osseointegrated implants. MATERIALS AND METHODS: The patient had
      two implants installed in the mastoid region that were linked by a bar, and a
      clip-type system was used. The ear prosthesis was constructed from medical-use
      silicone, pigmented to match the patient's skin colour and linked to the
      retention system. CONCLUSION: The patient's rehabilitation was satisfactory from
      both a functional and an aesthetic point of view, making it possible for the
      patient to return to a normal social life and regain lost self-esteem.

PMID- 22612827
TI  - Geriatric dentistry--meet the need.
AB  - Geriatric dentistry or gerodontics is the delivery of dental care to older adults
      involving the diagnosis, prevention, and treatment of problems associated with
      normal ageing and age-related diseases as part of an inter-disciplinary team with
      other health care professionals. Geriatric health is an ignored and under
      explored area worldwide. Oral health reflects overall well being for the elderly
      population. Conversely, elderly patients are more predisposed to oral conditions
      due to age-related systemic diseases and functional changes. The major barriers
      to practising geriatric dentistry are the lack of trained faculty members, a
      crowded curriculum and monetary concerns. For successful treatment, the
      practitioner must adopt a humanitarian approach and develop a better
      understanding of the feelings and attitudes of the elderly. Prevention and early
      intervention strategies must be formulated to reduce the risk of oral diseases in
      this population. In future, dental professionals must have a proper understanding
      of the magnitude of the services to be provided to the elderly. This could only
      be realised through an education programme in geriatric dentistry, which should
      be started without further delay. This article hence sets out the objectives,
      needs, present scenario, strategies and types of dental treatment required by the
      elderly population.

PMID- 22612828
TI  - Asymptomatic nodules of the upper lip: report of a canalicular adenoma with
      immunoprofile presentation.
AB  - Canalicular adenoma is an uncommon benign tumour that generally arises in the
      minor salivary glands of individuals over 60 years old. This study illustrates a
      case of canalicular adenoma in a 70-year-old female, presenting as two distinct
      asymptomatic nodules in the upper lip. Immunohistochemistry analysis was
      performed. Clinical features, management, histology and immunoprofile from this
      case and from the literature are discussed.

PMID- 22612829
TI  - Prevention of trauma to edentulous ridge from opposing natural teeth.
AB  - OBJECTIVE: To suggest a technique to prevent trauma of the edentulous ridge from
      opposing natural or restored teeth. BACKGROUND: The prevalence of the condition
      where one edentulous arch opposes a natural or restored dentition is quite
      common. In most of cases, the maxillary arch is completely edentulous and either
      all teeth or only anterior teeth are present in the mandibular arch. These
      remaining teeth may continuously cause trauma to the opposing edentulous ridge
      during the night when a removable prosthesis is kept out of the mouth. MATERIALS
      AND METHODS: A thermoplastic acrylic resin mouthguard was fabricated on a cast of
      the remaining teeth dentition. CONCLUSION: This article presents a simple and
      inexpensive procedure to prevent self-induced trauma of the edentulous ridge from
      opposing natural teeth by using a thermoplastic acrylic resin mouthguard.

PMID- 22612830
TI  - Orthodontic treatment in an elderly patient with extraction of upper premolar.
AB  - In the past few years, life expectancy of the world's population has gradually
      increased and as a result the number of elderly patients seeking orthodontic
      treatment is becoming higher. The objective of this work is to report a clinical
      case of orthodontic treatment of an elderly patient in which a dental extraction
      was performed to correct the relationship between upper and lower arches. The
      results favoured an improved dental arch relationship and promoted adequate
      aesthetics and function.

PMID- 22612831
TI  - Oral desmoplastic melanoma mimicking inflammatory hyperplasia.
AB  - INTRODUCTION: Desmoplastic melanoma (DM) arising in the oral cavity is a rare
      neoplasm that may be confused with a variety of non-melanocytic benign or
      malignant lesions. OBJECTIVES: To present a case of DM in the oral mucosa
      mimicking fibrous inflammatory hyperplasia, discusses the difficulties involved
      in the diagnosis and offers a literature review on the clinicopathologic and
      immunohistochemincal aspects of this neoplasm. CASE REPORT: A 62-year-old white
      male, smoker, was referred with a chief complaint of pain and swelling in the
      palate. The oral examination revealed multiple brown-to-black patches and a non
      pigmented sessile nodule located on the mucosa of the hard palate. The clinical
      diagnosis of the pigmented lesions was either oral melanosis or melanoma. The
      nodular lesion was clinically diagnosed as fibrous inflammatory hyperplasia.
      Incisional biopsy was performed on the pigmented lesion and the microscopic
      sections revealed a melanotic macule. The nodular lesions histologically revealed
      an amelanotic desmoplastic melanoma. CONCLUSIONS: Reactive lesions close to a
      pigmented area should be investigated with great care.

PMID- 22612832
TI  - Leishmaniasis with oral mucosa involvement.
AB  - INTRODUCTION: The term leishmaniasis comprises a group of diseases caused by
      different protozoan species of the genus Leishmania. There are three main
      clinical forms of leishmaniasis: visceral, cutaneous and mucocutaneous. Exclusive
      involvement of the mucosa is very rare. OBJECTIVES: To present a case of
      mucocutaneous leishmaniasis in an elderly patient, discuss the clinical
      presentation, diagnostic process and treatment emphasizing the distinctions from
      other granulomatous lesions. CASE REPORT: A 71-year-old male presenting with a
      symptomatic lesion on the hard and soft palate, which had developed over a period
      of 6 months was evaluated. The oral exam revealed a lesion with multiple
      ulcerated nodules on the hard and soft palate extending to the oropharynx. The
      diagnostic hypothesis was chronic infectious disease (paracoccidioidomycose,
      tuberculosis and leishmaniasis) or squamous cell carcinoma. Histopathological,
      histochemical and immunohistochemical analysis were performed. A chest x-ray
      revealed a normal pulmonary pattern. The Montenegro skin test was positive. The
      definitive diagnosis was leishmaniasis with exclusive oral manifestation and the
      patient was treated with liposomal amphotericin. CONCLUSIONS: Localized oral
      mucosa leishmaniasis is an uncommon event in an immunocompetent patient. Dentists
      play an important role in the diagnosis of oral leishmaniasis, which has systemic
      repercussions.

PMID- 22612833
TI  - CAD/CAM treatment for the elderly--a case report.
AB  - BACKGROUND: When elderly develop signs and symptoms of Alzheimer's disease they
      lose their independence and neglect dental hygiene. Dentists are increasingly
      confronted by seniors who are in need but who have limited access to dental care.
      Caretakers and family are also often confronted with behaviour problems besides
      the dental problems. OBJECTIVE: To report the importance of shorter and lower
      impact treatment for seniors when caretakers and family are confronted with a
      behavioural problem in addition to the dental problem. MATERIALS AND METHODS: In
      this case report, the oral management of a patient with Alzheimer's disease was
      described using chairside computer-aided design/computer-aided manufacturing
      (CAD/CAM) technology while constructing a bonded bridge. DISCUSSION: The case
      report emphasises the importance of interaction with the patient and added a
      treatment method for patients with limited cognitive skills who become easily
      agitated or aggressive. CONCLUSION: The fabrication of a full ceramic bonded
      bridge utilising the Cerec 3D chairside CAD/CAM technology in an Alzheimer
      patient has been shown to be a feasible, precise, aesthetic and durable solution.
      It added a technique for intervening with patients with limited tolerance for
      dental procedures, which improves the quality of life of both patient and family.

PMID- 22612835
TI  - Surgical and prosthetic treatment in an elderly patient affected by unilateral
      idiopathic gingival fibromatosis: a case report.
AB  - OBJECTIVES: The aim was to present the diagnosis and treatment of a case of
      unilateral idiopathic gingival fibromatosis (IGF) in a geriatric patient.
      BACKGROUND: IGF is a rare condition characterised by an enlargement of the
      attached and marginal gingivae with no obvious association to any causative
      factor. Gingival overgrowth causes inaesthetic changes and clinical symptoms such
      as speech disturbances, tooth movement, and occlusal problems. MATERIALS AND
      METHODS: A 65-year-old female presented localised enlargement of mandibular
      gingiva, malpositioning of anterior mandibular teeth, and difficulty in speech
      and mastication. IGF also causes numerous aesthetic and psychological problems.
      Treatment consisted of multiple extractions, surgical therapy, and early
      prosthetic rehabilitation to restore function and appearance and to prevent
      recurrence. RESULTS: Excellent aesthetic result and psychological benefit were
      achieved, and no fibromatosis recurrence was detected after 1 year following
      surgery. CONCLUSION: Gingival resection of the tissue excess and early oral
      rehabilitation with removable dentures have so far greatly improved patient's
      quality of life.

PMID- 22612834
TI  - Implant-supported palatal lift prosthesis in a patient with velopharyngeal
      incompetence: a case report.
AB  - OBJECTIVE: To describe the use of dental implants in the treatment of
      velopharyngeal incompetence. BACKGROUND: Velopharyngeal incompetence is
      characterized by the inability to contract the tissues of the soft palate. The
      most common causes are neuromuscular problems resulting from concussion and
      degenerative conditions of the central nervous system. MATERIALS AND METHODS: The
      treatment using palatal lift prosthesis is well established in the literature;
      however, reports on the use of osseointegrated implants are scarce.
      Rehabilitation using only this type of fibromucosal support is difficult in
      edentulous patients, since the prosthesis has a palatal lift extension. RESULTS:
      The implants provided retention and stability to the prosthesis, improving
      swallowing and speech and contributing to improve the patient's quality of life.
      CONCLUSION: This article reports the rehabilitation of a patient with a totally
      edentulous maxilla with velopharyngeal incompetence using an implant-retained
      palatal lift prosthesis.

PMID- 22612837
TI  - Unnoticed swallowing of a unilateral removable partial denture.
AB  - OBJECTIVE: This paper presents a case report about an unnoticed swallowing of a
      partial denture impacted in the esophagus in a 74-year old man without serious
      complications. BACKGROUND DATA: Dental prostheses (removable/fixed dental
      prostheses or fragments of dentures) appear to constitute a significant
      proportion of swallowed of impacted foreign bodies in the orolaryngopharynx.
      CONCLUSION: This case emphazises that is advisable to contraindicate this type of
      unilateral removable partial denture to replace teeth as temporary or definitive
      dental prosthesis.

PMID- 22612836
TI  - Management of a dentigerous cyst in a medically compromised geriatric patient: a
      case report.
AB  - BACKGROUND: Because of the increasing number of older persons seeking dental
      care, the growing trend towards a longer dental appointment and increased
      administration of drugs in dentistry, the possibility of occurrence of medical
      emergencies in dental offices has shown an upward trend. OBJECTIVE: This case
      report discusses enucleation of a central dentigerous cyst in a 72-year old male
      on long-term low dose aspirin therapy. MATERIAL AND METHODS: Surgical removal of
      impacted tooth with total enucleation of cystic lesion was performed in the
      dental chair under 2% lidocaine with 1:200,000 adrenaline, 3 days after aspirin
      cessation. After complete debridement of the surgical site, the wound was sutured
      and a gauge saturated with 10% tranexamic acid was placed on surgical site for 30
      minutes. RESULT: No post-operative complications or bleeding was seen on
      subsequent appointment and healing was normal. CONCLUSION: A geriatric and
      medically compromised patient demands special care and attention; and the
      decision to cease aspirin before surgery or not is of critical importance.

PMID- 22612838
TI  - Gingival overgrowth in partially edentulous ridges in an elderly female patient
      with epilepsy: a case report.
AB  - BACKGROUND: Drug-influenced gingival overgrowth is an unaesthetic overgrowth of
      gingiva principally associated with intake of drugs like phenytoin, cyclosporin A
      and nifedipine. Its occurrence in both dentate and edentulous regions of oral
      cavity is poorly understood. OBJECTIVES: This report highlights clinical and
      histological description, aetiology and management of gingival overgrowth in a
      partially edentulous (non-denture wearer) 60-year-old female patient with
      epilepsy on phenytoin and phenobarbital drugs from past 7 years. MATERIALS AND
      METHODS: Patient's intraoral examination revealed lobulated and fibrotic
      consistency gingival overgrowth around teeth and on partially edentulous ridges
      of upper and lower arches along with generalised tooth mobility. Under medical
      consultation, full mouth extraction, surgical excision of overgrowth followed by
      complete denture rehabilitation and replacement of combination drugs with sodium
      valproate were accomplished. RESULTS: Histologically, the lesion showed fibro
      epithelial hyperplasia. Clinical results after 6 months demonstrated almost
      complete resolution of gingival overgrowth. CONCLUSION: The findings of present
      case suggest that gingival overgrowth can occur even in partially edentulous
      ridges (not exposed to denture wear) that could be due to persistence of gingival
      overgrowth, which may not resolve completely following tooth extraction or occurs
      because of incorporation of specific subpopulation of gingival fibroblasts in
      alveolar ridge mucosa.

PMID- 22612839
TI  - Langerhans's cell histiocytosis in old subjects: two rare case reports and review
      of the literature.
AB  - BACKGROUND: Langerhans cell histiocytosis (LCH) is a proliferative disease of
      histiocyte-like cells that generally affects children; LCH onset is rare in
      adults; immunohistochemistry is essential to obtain the correct diagnosis, and
      treatment protocols are controversial. OBJECTIVE: To describe two new cases of
      adult onset oral LCH. CASE REPORTS: Case 1: a 71-year-old woman, complaining of
      diffuse oral pain, presented with erythematous mucosal lesions; the panoramic
      radiograph and CT scan showed multiple mandible radiolucent areas.
      Immunohistochemical assay for S-100, CD1a and langerin test was essential in
      reaching the correct diagnosis. Case 2: a 77-year-old female patient presented
      with a non-painful, non-bleeding, slightly elevated erythematous palatal lesion
      of 6 months duration, together with a genital vulvar lesion of uncertain nature.
      The pathology confirmed the diagnosis of LCH. Many therapies (etoposid,
      radiotherapy) could induce only a clinical partial remission; Cladribine induced
      a complete recovery. CONCLUSION: The first case was difficult to diagnose: the
      clinical presentation and course of the disease (LCH) in the elderly are multiple
      and unpredictable. An immunohistochemistry study is often essential to obtain the
      correct diagnosis. The second case required several therapeutic interventions:
      even though some cases regress spontaneously, others require systemic
      chemotherapy.

PMID- 22612840
TI  - Undergraduate geriatric education through community service learning.
AB  - INTRODUCTION: Despite the exponential growth of the elderly population worldwide,
      geriatric education has been a formal component of only a few dental schools'
      curricula. OBJECTIVE: To describe the geriatric community service learning (CSL)
      component of the professionalism and community service (PACS) module, and to
      explore a CSL project carried out by a group of first year dental students at a
      long-term care facility. METHODS: A literature review was performed to present
      and describe the CSL component of the PACS module. Students' personal reflections
      were used to illustrate some of the joys and challenges of experiencing a long
      term care facility environment. RESULTS: The newly developed PACS module combines
      community service learning with the long-term care experience. Students develop,
      apply and evaluate an educational health promotion activity in a long-term care
      facility. CONCLUSIONS: The PACS module has encouraged students to acquire
      comprehensive knowledge and awareness of the needs and dynamics of a long-term
      care as they collaboratively interacted with personnel from the facility to
      develop their projects. The authors would like to engage other schools in
      discussing the need to integrate community-based geriatric education into their
      dental curricula.

PMID- 22612841
TI  - Oral malignant melanoma--an unusual presentation.
AB  - Malignant melanoma is the least common but most deadly of all primary skin
      cancers. Oral malignant melanoma is a rare aggressive neoplasm usually seen in
      middle aged persons. This malignancy is more frequently seen on the hard palate
      and gingiva. Oral melanomas are associated with very poor prognosis because of
      the tendency to metastasise or invade tissues locally more readily than other
      malignant tumours of the oral cavity especially in the case of a geriatric
      patient. The surgical approach, combined with the chemotherapy, is the first
      choice treatment. This report highlights a case report of 71-year-old female
      patient diagnosed and treated surgically for an oral malignant melanoma of the
      pedunculated variety affecting the hard palate and gingiva with review of
      literature.

PMID- 22612843
TI  - A 30-year review of a geriatric dentistry teaching programme.
AB  - OBJECTIVE: To review the development of the Geriatric Dental and Special Needs
      Education programme at the University of Iowa over the last 30 years. BACKGROUND:
      The programme at Iowa evolved from a didactic elective programme taught by a
      single faculty person to a required didactic and clinical programme, which
      includes a Special Care Clinic in the dental school and a mobile unit with
      portable dental equipment which serves ten area nursing homes with comprehensive
      care. MATERIALS AND METHODS: Changes have been made in the programme over time
      based on formal and informal feedback from students and graduates, and we have
      also looked at the impact of the programme on dental services to our target
      population. RESULTS: The factors influencing the curriculum development are
      identified and discussed. CONCLUSION: As no dental schools are the same, some
      general applications are suggested from the Iowa experience.

PMID- 22612842
TI  - Effect of electromagnetic field on bone regeneration around dental implants after
      immediate placement in the dog mandible: a pilot study.
AB  - BACKGROUND: Accelerating bone healing around dental implants can reduce the long
      term period between the insertion of implants and functional rehabilitation.
      OBJECTIVE: This in vivo study evaluated the effect of a constant electromagnetic
      field (CEF) on bone healing around dental implants in dogs. MATERIALS AND
      METHODS: Eight dental implants were placed immediately after extraction of the
      first pre-molar and molar teeth on the mandible of two male dogs and divided into
      experimental (CEF) and control groups. A CEF at magnetic intensity of 0.8 mT with
      a pulse width of 25 MUs and frequency of 1.5 MHz was applied on the implants for
      20 min per day for 2 weeks. RESULT AND CONCLUSION: After qualitative histological
      analysis, a small quantity of newly formed bone was observed in the gap between
      the implant surface and alveolar bone in both groups.

PMID- 22612844
TI  - Social interactions, body image and oral health among institutionalised frail
      elders: an unexplored relationship.
AB  - OBJECTIVES: This paper draws on theories of ageing, body image and disfigurement,
      to explore the potential for relationships between oral health, body image and
      social interactions between institutionalised elders. BACKGROUND: Social
      relationships are important at all stages of life. A positive body image
      increases confidence in social interactions, which contributes substantially to
      health, well-being and quality of life. Body image can be negatively impacted by
      oral conditions, particularly those that are appearance related and do not meet
      cultural ideals. RESULTS: Typically, the oral health of frail elders in long-term
      care facilities is poor, but to what extent poor oral health and dysfunction
      influence body image, and social behaviours is unclear. CONCLUSIONS: We conclude
      that there is the potential for poor oral health conditions to contribute
      negatively to the social well-being in this population, but suggest that it
      requires further investigation.

PMID- 22612845
TI  - Antifungal and physical characteristics of modified denture base acrylic
      incorporated with silver nanoparticles.
AB  - OBJECTIVE: This study evaluated the antifungal and physical characteristics of
      denture base acrylic combined with silver nanoparticles. MATERIALS AND METHODS:
      Polymerized denture acrylic disc specimens containing 0 (control), 1.0, 5.0,
      10.0, 20.0 and 30.0 wt% of silver nanoparticles were placed on separate culture
      plate dish and 100 iL samples of yeast suspension of Candida albicans strain were
      inoculated on each specimens and incubated at 37 degrees C, for 24 h. The
      antifungal effects were evaluated as a number of viable cells in retrieved fungal
      suspension. To characterize physical aspects, specimens were tested for elution
      of silver cation (Ag(+)) at 24 h and 30th day, thermal analysis (TG/DTA),
      scanning electron microscope and energy dispersed X-ray analysis (SEM/EDX) and
      color stability. RESULTS: Significant reduced CFU was exhibited at 20.0 and 30.0
      wt% of silver nanoparticles incorporated (p < 0.01) and Ag(+) elution from
      specimens (maximum 0.356 +/- 0.11 mg/L) contributed little to the antifungal
      activity considering MIC of Ag(+) in this study (3.0 mg/L). The successful
      synthesis of modified denture acrylic containing silver nanoparticles was
      accessed by TG/DTA and EDX analysis. CONCLUSION: The modified denture base
      acrylic combined with silver nanoparticles displayed antifungal properties and
      acted like latent antifungal material itself with low-releasing Ag(+), however,
      the improvement of poor color stability was still required.

PMID- 22612847
TI  - Local recurrence and assessment of sentinel lymph node biopsy in deep soft tissue
      leiomyosarcoma of the extremities.
AB  - BACKGROUND: Leiomyosarcoma of deep soft tissues of the extremities is a rare
      malignant tumour treated primarily by surgery. The incidence of local recurrence
      and lymph node metastasis is uncertain and it is not known whether a sentinel
      lymph node biopsy is indicated in these tumours. METHODS: A retrospective review
      of patients treated for extremity deep soft tissue leiomyosarcoma at our
      institution over a 10-year period was conducted. Patients developing local
      recurrence or lymph node metastasis were identified. The presence or absence of
      lymphatics in the primary tumours was assessed by immunohistochemical expression
      of LYVE-1 and podoplanin. RESULTS: 27 patients (mean age 62 years) were included
      in the study. 15 were female and 12 male. Lymph node metastasis was seen in only
      two cases (7%); intratumoural lymphatics were identified in the primary tumours
      of both these cases. Local recurrence occurred in 25.9% of cases despite complete
      excision and post-operative radiotherapy; the mean time to recurrence was 10.1
      months. CONCLUSION: On the basis of this study, we do not advocate sentinel lymph
      node biopsy in this group of patients except in those cases in which
      intratumoural lymphatics can be demonstrated. Close follow up is important
      especially for high grade leiomyosarcomas, particularly in the first year, as
      these tumours have a high incidence of local recurrence.

PMID- 22612848
TI  - A survey on illegal and counterfeit medicines for the treatment of erectile
      dysfunctions in Italy.
AB  - INTRODUCTION: In developed countries the phenomenon of pharmaceutical
      counterfeiting is steadily increasing through the illegal and the Internet
      market. Medicines for the treatment of erectile dysfunctions containing
      phosphodiesterase type 5 inhibitors (PDE5) are especially prone to falsification.
      AIMS: To obtain evidence of the health risks for patients taking these products
      and to provide useful information to general practitioners and specialists in
      sexual medicine. METHODS: First the samples were visually inspected and then
      analyzed to get information about their identity and quality. MAIN OUTCOME
      MEASURES: A survey on the PDE5 medicines analyzed by the Italian official
      medicines control laboratory between 2005 and 2011 was performed. All the
      analyzed medicines were gathered from the Italian illegal market (seizures by
      police forces) or were bought from illegal online pharmacies. Results.  The study
      revealed that 24% of the analyzed samples were counterfeit and 54% were illegal
      medicines. In 12% of the cases an intermediate classification
      (illegal/counterfeit) was assigned. Only 7% of the samples were original.
      Moreover, the examination of the packaging evidenced potential risks: outer and
      immediate packaging missing; inconsistency between the carton box and the blister
      as regards the expiry date and/or the batch number; expiry date or manufacturer's
      name or country missing. CONCLUSIONS: In 19% of the samples a potential health
      risk for patients was identified due to either the presence in the sample of more
      than one undeclared PDE5(s) or an amount of the active ingredient higher than
      that declared (up to 190% of the maximum dose) or to the presence of potentially
      dangerous excipients of non-pharmaceutical origin or quality (e.g., gypsum or non
      purified talc).

PMID- 22612846
TI  - Time-resolved vibrational spectroscopy of [FeFe]-hydrogenase model compounds.
AB  - Model compounds have been found to structurally mimic the catalytic hydrogen
      producing active site of Fe-Fe hydrogenases and are being explored as functional
      models. The time-dependent behavior of Fe(2)(MU-S(2)C(3)H(6))(CO)(6) and Fe(2)(MU
      S(2)C(2)H(4))(CO)(6) is reviewed and new ultrafast UV- and visible-excitation/IR
      probe measurements of the carbonyl stretching region are presented. Ground-state
      and excited-state electronic and vibrational properties of Fe(2)(MU
      S(2)C(3)H(6))(CO)(6) were studied with density functional theory (DFT)
      calculations. For Fe(2)(MU-S(2)C(3)H(6))(CO)(6) excited with 266 nm, long-lived
      signals (tau = 3.7 +/- 0.26 MUs) are assigned to loss of a CO ligand. For 355 and
      532 nm excitation, short-lived (tau = 150 +/- 17 ps) bands are observed in
      addition to CO-loss product. Short-lived transient absorption intensities are
      smaller for 355 nm and much larger for 532 nm excitation and are assigned to a
      short-lived photoproduct resulting from excited electronic state structural
      reorganization of the Fe-Fe bond. Because these molecules are tethered by
      bridging disulfur ligands, this extended di-iron bond relaxes during the excited
      state decay. Interestingly, and perhaps fortuitously, the time-dependent DFT
      optimized exited-state geometry of Fe(2)(MU-S(2)C(3)H(6))(CO)(6) with a
      semibridging CO is reminiscent of the geometry of the Fe(2)S(2) subcluster of the
      active site observed in Fe-Fe hydrogenase X-ray crystal structures. We suggest
      these wavelength-dependent excitation dynamics could significantly alter
      potential mechanisms for light-driven catalysis.

PMID- 22612849
TI  - Good pharmacovigilance practice and the curate's egg.

PMID- 22612850
TI  - Eosinophilic pneumonia in patients treated with daptomycin: review of the
      literature and US FDA adverse event reporting system reports.
AB  - BACKGROUND: Eosinophilic pneumonia (EP) has been noted in association with
      daptomycin use. The product labelling was recently updated to include EP in the
      Warnings and Precautions and Post-Marketing Experience sections. OBJECTIVE: The
      objective of this study was to analyse adverse event (AE) reports submitted to
      the US FDA as well as published cases to characterize the clinical features and
      course of EP in daptomycin-treated patients. METHODS: We searched for EP cases
      associated with daptomycin administration in the FDA Adverse Event Reporting
      System (AERS) submitted from 2004 to 2010, and the published literature. Cases
      were defined as definite, probable, possible and unlikely in terms of the
      diagnosis of EP and the potential association with daptomycin exposure. Definite
      cases had concurrent exposure to daptomycin, fever, dyspnoea with increased
      oxygen requirement or required mechanical ventilation, new infiltrates on chest
      imaging, bronchoalveolar lavage with >25% eosinophils and clinical improvement
      following daptomycin withdrawal. Additionally, we assessed inpatient daptomycin
      utilization. RESULTS: We identified 7 definite, 13 probable, 38 possible cases of
      daptomycin-induced EP, and 23 unlikely cases. The seven definite EP cases had
      resolution after daptomycin was stopped, including two with EP recurrence
      following daptomycin rechallenge. Regarding the definite cases: (i) ages ranged
      from 60 to 87 years; (ii) dosing ranged from 4.4 to 8.0 mg/kg/day; and (iii) EP
      developed 10 days to 4 weeks after starting daptomycin. There was a gradual
      increase in the number of patients with an inpatient hospital discharge billing
      for daptomycin from the year 2004 to 2010. CONCLUSIONS: We report 7 definite, 13
      probable and 38 possible EP cases associated with daptomycin administration. As
      AERS is based on voluntary reporting, the incidence of EP cannot be assessed.
      Healthcare providers should have heightened awareness of this serious AE
      associated with daptomycin use.

PMID- 22612851
TI  - Prevalence of QT interval prolongation in patients admitted to cardiac care units
      and frequency of subsequent administration of QT interval-prolonging drugs: a
      prospective, observational study in a large urban academic medical center in the
      US.
AB  - BACKGROUND: Cardiac arrest due to torsades de pointes (TdP) is a rare but
      catastrophic event in hospitals. Patients admitted to cardiac units are at higher
      risk of drug-induced QT interval prolongation and TdP, due to a preponderance of
      risk factors. Few data exist regarding the prevalence of QT interval prolongation
      in patients admitted to cardiac units or the frequency of administering QT
      interval-prolonging drugs to patients presenting with QT interval prolongation.
      OBJECTIVE: The aim of this study was to determine the prevalence of Bazett's
      corrected QT (QT(c)) interval prolongation upon admission to cardiac units and
      the proportion of patients presenting with QT(c) interval prolongation who are
      subsequently administered QT interval-prolonging drugs during hospitalization.
      METHODS: This was a prospective, observational study conducted over a 1-year
      period (October 2008-October 2009) in 1159 consecutive patients admitted to two
      cardiac units in a large urban academic medical centre located in Indianapolis,
      IN, USA. Patients were enrolled into the study at the time of admission to the
      hospital and were followed daily during hospitalization. Exclusion criteria were
      age <18 years, ECG rhythm of complete ventricular pacing, and patient designation
      as 'outpatient' in a bed and/or duration of stay <24 hours. Data collected
      included demographic information, past medical history, daily progress notes,
      medication administration records, laboratory data, ECGs, telemetry monitoring
      strips and diagnostic reports. All patients underwent continuous cardiac
      telemetry monitoring and/or had a baseline 12-lead ECG obtained within 4 hours of
      admission. QT intervals were determined manually from lead II of 12-lead ECGs or
      from continuous lead II telemetry monitoring strips. QT(c) interval prolongation
      was defined as >=470 ms for males and >=480 ms for females. In both males and
      females, QT(c) interval >500 ms was considered abnormally high. A medication was
      classified as QT interval-prolonging if there were published data indicating that
      the drug causes QT interval prolongation and/or TdP. Study endpoints were (i)
      prevalence of QT(c) interval prolongation upon admission to the Cardiac Medical
      Critical Care Unit (CMCCU) or an Advanced Heart Care Unit (AHCU); (ii) proportion
      of patients admitted to the CMCCU/AHCU with QT(c) interval prolongation who
      subsequently were administered QT interval-prolonging drugs during
      hospitalization; (iii) the proportion of these higher-risk patients in whom TdP
      risk factor monitoring was performed; (iv) proportion of patients with QT(c)
      interval prolongation who subsequently received QT-prolonging drugs and who
      experienced further QT(c) interval prolongation. RESULTS: Of 1159 patients
      enrolled, 259 patients met exclusion criteria, resulting in a final sample size
      of 900 patients. PATIENT CHARACTERISTICS: mean (+/- SD) age, 65 +/- 15 years;
      female, 47%; Caucasian, 70%. Admitting diagnoses: heart failure (22%), myocardial
      infarction (16%), atrial fibrillation (9%), sudden cardiac arrest (3%). QT(c)
      interval prolongation was present in 27.9% of patients on admission; 18.2% had
      QT(c) interval >500 ms. Of 251 patients admitted with QT(c) interval
      prolongation, 87 (34.7%) were subsequently administered QT interval-prolonging
      drugs. Of 166 patients admitted with QT(c) interval >500 ms, 70 (42.2%) were
      subsequently administered QT interval-prolonging drugs; additional QT(c) interval
      prolongation >=60 ms occurred in 57.1% of these patients. CONCLUSIONS: QT(c)
      interval prolongation is common among patients admitted to cardiac units. QT
      interval-prolonging drugs are commonly prescribed to patients presenting with
      QT(c) interval prolongation.

PMID- 22612852
TI  - Adverse Drug Reactions in Children--International Surveillance and Evaluation
      (ADVISE): a multicentre cohort study.
AB  - BACKGROUND: A previous meta-analysis reported that 9.5% of hospitalized children
      suffered from an adverse drug reaction (ADR); however, reported incidences among
      studies varied. OBJECTIVE: To enhance the knowledge of ADRs in paediatric
      hospitalized patients at a global level we investigated the incidence and
      characteristics of ADRs in hospitalized children in European and non-European
      countries. METHODS: A prospective observational cohort study was conducted in
      academic and non-academic hospitals in five countries: Australia, Germany, Hong
      Kong, Malaysia and the UK. Children aged 0-18 years admitted during a 3-month
      period (between 1 October 2008 and 31 December 2009) were recruited. The main
      outcome measures were incidence, causality and outcome of ADRs. RESULTS: A total
      of 1278 patients (1340 admissions) were included [Australia n = 146 (149
      admissions), Germany n = 376 (407), Hong Kong n = 143 (149), Malaysia n = 300
      (314) and the UK n = 313 (321)]. The median age was 2 years (interquartile range
      [IQR] 0-7). Patients received a total of 5367 drugs (median 3; IQR 2-5) and
      median length of hospital stay was 4 days (IQR 3-7). A total of 380 ADRs were
      identified in 211 patients. The resultant ADR incidence of 16.5% (95% CI 14.5,
      18.7) varied significantly between countries (p < 0.001). The highest incidences
      were observed in Malaysia and the UK. 65.3% (n = 248) of ADRs were found to be
      probable, and 24% of the ADRs were serious, with one being fatal. CONCLUSIONS: By
      comparing data from five countries in Europe, Asia and Australia we have shown
      that the incidence of ADRs in hospitalized children is at least as high as
      incidences published in adults. However, the variation between countries was
      mainly due to different populations and treatment strategies. Particular
      attention should be given to opioid use in hospitalized children.

PMID- 22612853
TI  - Early detection of pharmacovigilance signals with automated methods based on
      false discovery rates: a comparative study.
AB  - BACKGROUND: Improving the detection of drug safety signals has led several
      pharmacovigilance regulatory agencies to incorporate automated quantitative
      methods into their spontaneous reporting management systems. The three largest
      worldwide pharmacovigilance databases are routinely screened by the lower bound
      of the 95% confidence interval of proportional reporting ratio (PRR02.5), the
      2.5% quantile of the Information Component (IC02.5) or the 5% quantile of the
      Gamma Poisson Shrinker (GPS05). More recently, Bayesian and non-Bayesian False
      Discovery Rate (FDR)-based methods were proposed that address the arbitrariness
      of thresholds and allow for a built-in estimate of the FDR. These methods were
      also shown through simulation studies to be interesting alternatives to the
      currently used methods. OBJECTIVE: The objective of this work was twofold. Based
      on an extensive retrospective study, we compared PRR02.5, GPS05 and IC02.5 with
      two FDR-based methods derived from the Fisher's exact test and the GPS model
      (GPS(pH0) [posterior probability of the null hypothesis H0 calculated from the
      Gamma Poisson Shrinker model]). Secondly, restricting the analysis to GPS(pH0),
      we aimed to evaluate the added value of using automated signal detection tools
      compared with 'traditional' methods, i.e. non-automated surveillance operated by
      pharmacovigilance experts. METHODS: The analysis was performed sequentially, i.e.
      every month, and retrospectively on the whole French pharmacovigilance database
      over the period 1 January 1996-1 July 2002. Evaluation was based on a list of 243
      reference signals (RSs) corresponding to investigations launched by the French
      Pharmacovigilance Technical Committee (PhVTC) during the same period. The
      comparison of detection methods was made on the basis of the number of RSs
      detected as well as the time to detection. RESULTS: Results comparing the five
      automated quantitative methods were in favour of GPS(pH0) in terms of both number
      of detections of true signals and time to detection. Additionally, based on an
      FDR threshold of 5%, GPS(pH0) detected 87% of the RSs associated with more than
      three reports, anticipating the date of investigation by the PhVTC by 15.8 months
      on average. CONCLUSIONS: Our results show that as soon as there is reasonable
      support for the data, automated signal detection tools are powerful tools to
      explore large spontaneous reporting system databases and detect relevant signals
      quickly compared with traditional pharmacovigilance methods.

PMID- 22612854
TI  - Novel adverse events of bevacizumab in the US FDA adverse event reporting system
      database: a disproportionality analysis.
AB  - BACKGROUND: Bevacizumab is the first in its class, vascular endothelial growth
      factor (VEGF) inhibitor that was initially approved by the US FDA in 2004 for the
      treatment of metastatic colon cancer and other solid tumors. Preapproval clinical
      trials, particularly for oncology drugs, are limited in their ability to detect
      certain adverse effects and, therefore, the FDA and pharmaceutical sponsors
      collect and monitor reports of adverse events (AEs) following approval.
      OBJECTIVE: The purpose of this study was to screen the FDA's Adverse Event
      Reporting System (AERS) database for novel AEs that may be attributed to
      bevacizumab. METHODS: The FDA AERS database was used to identify all AE reports
      for bevacizumab from February 2004 to September 2009. Disproportionality analysis
      was conducted for bevacizumab against all other drugs in the background by
      setting statistical significance at proportional reporting ratio (PRR) >=2,
      observed case count >=3 and chi-square >=4. Subsequent clinical evaluation was
      performed to determine the clinical relevance of the findings and to group
      related events. RESULTS: A total of 523 Preferred Terms (PTs) were
      disproportionally reported; following clinical review 63 (12%) were found to be
      both unlabelled and of clinical importance. These PTs were grouped into 15
      clinical disorder groups. Among the clinical disorders, electrolyte abnormalities
      had the greatest number of reports (n = 426) followed by cardiovascular events (n
      = 421), gastrointestinal events (n = 345), nervous system disorders (n = 106) and
      pneumonitis (n = 96). On sensitivity analysis, a number of clinically important
      unlabelled disorders, such as necrotizing fasciitis, vessel wall disorders,
      arrhythmia and conduction disorder and autoimmune thrombocytopenia still met the
      statistical significance criteria. CONCLUSIONS: During the study period, out of
      12 010 AE reports mentioning bevacizumab, it was listed as the suspect drug in
      94.2% of the reports. Our disproportionality analysis identified many events that
      are already recognized as AEs of bevacizumab, but it also identified a number of
      clinically important unlabelled terms, which if confirmed in future studies would
      have potential implications for use of bevacizumab in clinical practice.

PMID- 22612855
TI  - Angle-resolved Raman imaging of interlayer rotations and interactions in twisted
      bilayer graphene.
AB  - Few-layer graphene is a prototypical layered material, whose properties are
      determined by the relative orientations and interactions between layers. Exciting
      electrical and optical phenomena have been observed for the special case of
      Bernal-stacked few-layer graphene, but structure-property correlations in
      graphene which deviates from this structure are not well understood. Here, we
      combine two direct imaging techniques, dark-field transmission electron
      microscopy (DF-TEM) and widefield Raman imaging, to establish a robust, one-to
      one correlation between twist angle and Raman intensity in twisted bilayer
      graphene (tBLG). The Raman G band intensity is strongly enhanced due to a
      previously unreported singularity in the joint density of states of tBLG, whose
      energy is exclusively a function of twist angle and whose optical transition
      strength is governed by interlayer interactions, enabling direct optical imaging
      of these parameters. Furthermore, our findings suggest future potential for novel
      optical and optoelectronic tBLG devices with angle-dependent, tunable
      characteristics.

PMID- 22612856
TI  - Molecular characterization of immunoinhibitory factors PD-1/PD-L1 in chickens
      infected with Marek's disease virus.
AB  - BACKGROUND: An immunoinhibitory receptor, programmed death-1 (PD-1), and its
      ligand, programmed death-ligand 1 (PD-L1), are involved in immune evasion
      mechanisms for several pathogens causing chronic infections and for neoplastic
      diseases. However, little has been reported for the functions of these molecules
      in chickens. Thus, in this study, their expressions and roles were analyzed in
      chickens infected with Marek's disease virus (MDV), which induces
      immunosuppression in infected chickens. RESULTS: A chicken T cell line, Lee1,
      which constitutively produces IFN-gamma was co-cultured with DF-1 cells, which is
      a spontaneously immortalized chicken fibroblast cell line, transiently expressing
      PD-L1, and the IFN-gamma expression level was analyzed in the cell line by real
      time RT-PCR. The IFN-gamma expression was significantly decreased in Lee1 cells
      co-cultured with DF-1 cells expressing PD-L1. The expression level of PD-1 was
      increased in chickens at the early cytolytic phase of the MDV infection, while
      the PD-L1 expression level was increased at the latent phase. In addition, the
      expression levels of PD-1 and PD-L1 were increased at tumor lesions found in MDV
      challenged chickens. The expressions levels of PD-1 and PD-L1 were also increased
      in the spleens and tumors derived from MDV-infected chickens in the field.
      CONCLUSIONS: We demonstrated that the chicken PD-1/PD-L1 pathway has
      immunoinhibitory functions, and PD-1 may be involved in MD pathogenesis at the
      early cytolytic phase of the MDV infection, whereas PD-L1 could contribute to the
      establishment and maintenance of MDV latency. We also observed the increased
      expressions of PD-1 and PD-L1 in tumors from MDV-infected chickens, suggesting
      that tumor cells transformed by MDV highly express PD-1 and PD-L1 and thereby
      could evade from immune responses of the host.

PMID- 22612857
TI  - Wood anatomical responses of oak saplings exposed to air warming and soil
      drought.
AB  - Water is vital for plant performance and survival. Its scarcity, induced by a
      seasonal decline in soil water availability or an increase of evaporative demand,
      can cause failures of the water conducting system. An adequate tolerance to
      drought and the ability to acclimate to changing hydraulic conditions are
      important features for the survival of long-lived woody plants in dry
      environments. In this study we examine secondary growth and xylem anatomical
      acclimation of 6 year old saplings of three European oak species (Quercus robur,
      Q. petraea, Q. pubescens) during the third consecutive year of exposure to soil
      drought and/or air warming (from 2007 to 2009). Intra-annual pinning was applied
      to mark the development of the formation of the annual ring 2009. Vessel size,
      parenchyma cell density and fiber size produced at different time of the growing
      season 2009 were compared between drought and warming treatments and species.
      Drought reduced secondary growth and induced changes in xylem structure while air
      warming had little effect on wood anatomical traits. Results indicate that
      drought-exposed saplings adjust their xylem structure to improve resistance and
      repairing abilities after cavitation. All species show a significant radial
      growth reduction, a reduced vessel size with diminished conductivity and a
      slightly increased density of parenchyma cells. Comparisons between species
      fostered our understanding of the relationship between the inter-specific xylem
      hydraulic plasticity and the ecological response to drought. The stronger changes
      observed for Q. robur and Q. petraea indicate a lower drought tolerance than Q.
      pubescens.

PMID- 22612859
TI  - Spectrum of autoantibodies in Tunisian psychiatric inpatients.
AB  - One hundred and three psychiatric inpatients (74 men) were assessed for a wide
      spectrum of autoantibodies including antinuclear, antismooth muscle,
      antimitochondrial, antiDNA, anti-phospholipid, anti-cardiolipin IgG and IgM,
      antikeratin, rheumatoid factor, antithyroperoxydase, antigliadin IgA and IgG,
      antitransgutaminase, and antiendomysium antibodies. Four groups of patients were
      considered separately, including 47 with schizophrenia, 23 with schizoaffective
      disorder, 16 with bipolar disorder and 17 patients with other different
      psychiatric diagnosis. Forty one healthy, age- and sex-matched blood donors were
      used as a control group. There were no significant difference in the prevalence
      of the different autoantibodies between patients (N = 103) and controls except
      for antigliadin IgG (30.1 vs 9.8 respectively, p = 0.01). Presence of
      autoantibodies was influenced by age but not by sex or treatment. As for
      diagnosis categories, patients with bipolar disorder presented significantly more
      autoantibodies than the three other categories and controls. These results point
      out a possible autoimmune activation in at least a subgroup of psychiatric
      patients especially amongst those suffering from bipolar disorder.

PMID- 22612858
TI  - Blood transfusion practice in a rural hospital in Northern Ghana, Damongo, West
      Gonja District.
AB  - BACKGROUND: Blood transfusion in rural sub-Saharan Africa presents special
      challenges. Transfusions are primarily given for emergencies--life-threatening
      blood loss or anemia; blood is usually collected from family or replacement
      donors; and facilities to store an adequate reserve in a hospital bank are
      constrained. We report the everyday and organizational practices in a medium
      sized district hospital in Northern Ghana. STUDY DESIGN AND METHODS: Information
      and data on blood transfusion practices at West Gonja Hospital, Damongo, were
      available from the laboratory reports, from day books and workbooks, and from
      direct observation in the following four areas: blood collection and blood
      donors; blood donation testing; blood storage and logistics; and clinical
      transfusion practice, adverse events, and follow-up. RESULTS: The hospital serves
      a rural community of 86,000. In 2009, a total of 719 units of whole blood were
      collected, a rate of 8.36 units per 1000 population. All donors were family or
      replacement donors. Positivity rates for infectious disease markers were 7.5%
      (64/853) for hepatitis B surface antigen, 6.1% (50/819) for hepatitis C virus,
      3.9% (33/846) for human immunodeficiency virus, and 4.7% (22/468) for syphilis.
      Supply of laboratory materials was sometimes problematic, especially for
      temperature-critical materials. Difficulties in sample labeling, storage of blood
      and laboratory supplies, and disposal of waste were also incurred by operational,
      material, and financial constraints. Follow-up for outcomes of transfusion is not
      currently feasible. CONCLUSIONS: The operational, demographic, and financial
      environment pertaining in a rural hospital in Northern Ghana differs
      substantially from that in which much of current blood transfusion practice and
      technology evolved. Considerable effort and innovation will be needed to address
      successfully the challenges posed.

PMID- 22612860
TI  - The fate of the oculomotor system in clinical bilateral anophthalmia.
AB  - The interdependence of the development of the eye and oculomotor system during
      embryogenesis is currently unclear. The occurrence of clinical anophthalmia,
      where the globe fails to develop, permits us to study the effects this has on the
      development of the complex neuromuscular system controlling eye movements. In
      this study, we use very high-resolution T2-weighted imaging in five anophthalmic
      subjects to visualize the extraocular muscles and the cranial nerves that
      innervate them. The subjects differed in the presence or absence of the optic
      nerve, the abducens nerve, and the extraocular muscles, reflecting differences in
      the underlying disruption to the eye's morphogenetic pathway. The oculomotor
      nerve was present in all anophthalmic subjects and only slightly reduced in size
      compared to measurements in sighted controls. As might be expected, the presence
      of rudimentary eye-like structures in the socket appeared to correlate with
      development and persistence of the extraocular muscles in some cases. Our study
      supports in part the concept of an initial independence of muscle development,
      with its maintenance subject to the presence of these eye-like structures.

PMID- 22612862
TI  - MRI-based multiparametric strain analysis predicts contractile recovery after
      aortic valve replacement for aortic insufficiency.
AB  - BACKGROUND: Guidelines for referral of chronic aortic insufficiency (AI) patients
      for aortic valve replacement (AVR) suggest that surgery can be delayed until
      symptoms or reduction in left ventricular (LV) contractile function occur. The
      frequent occurrence of reduced LV contractile function after AVR for chronic AI
      suggests that new contractile metrics for surgical referral are needed. METHODS:
      In 16 chronic AI patients, cardiac MRI tagged images were analyzed before and
      21.5 +/- 13.8 months after AVR to calculate LV systolic strain. Average
      measurements of three strain parameters were obtained for each of 72 LV regions,
      normalized using a normal human strain database (n = 63), and combined into a
      composite index (multiparametric strain z score [MSZ]) representing standard
      deviation from the normal regional average. RESULTS: Preoperative global MSZ (72
      region average) correlated with post-AVR global MSZ (R(2) = 0.825, p < 0.001).
      Preoperative global MSZ also predicts improvement of impaired regions (N = 271
      regions from 14 AI patients, R(2) = 0.392, p < 0.001). Preoperative MRI-based LV
      ejection fraction (LVEF) is also predictive (r = 0.410, p < 0.001). Although
      global preoperative MSZ had a significantly higher correlation than preoperative
      LVEF with improvement of injured regions (p < 0.001), both measures convey the
      same phenomenon. CONCLUSIONS: Global preoperative MRI-based multiparametric
      strain predicts global strain postoperatively, as well as improvement of regions
      (n = 72 per LV) with impaired contractile function. Global contractile function
      is an important correlate with improvement in regionally impaired contractile
      function, perhaps reflecting total AI volume-overload burden (severity/duration
      of AI).

PMID- 22612863
TI  - End-of-life spiritual care at a VA medical center: chaplains' perspectives.
AB  - OBJECTIVE: Spiritual care is an essential component of quality palliative care.
      Recognizing the importance, the Department of Veterans Affairs (VA) mandates the
      inclusion of chaplains in a palliative care consult team (PCCT). The purpose of
      this study is to explain the process and content of spiritual care provided in a
      VA Medical Center from chaplains' perspectives. METHOD: Five Christian chaplains
      who provide care to patients at end of life were interviewed. Each interview was
      recorded and transcribed. Analysis based on the grounded theory was used to
      identify themes from each interview question. RESULTS: The PCCT in this study
      appeared to have a strong referral and communication system in which every
      palliative care patient was seen by a chaplain and the care plan was discussed
      with an interdisciplinary team. Chaplains reported providing a range of services,
      which addressed religious, spiritual, emotional, family, and illness concerns.
      Chaplains were aware of the unique spiritual needs of veterans, including working
      through guilt for killing in war and requiring forgiveness. Chaplains' ideas for
      improvement of spiritual care services included increasing time to provide care,
      providing bereavement care and support to families, and adding chaplains with
      different religious backgrounds. Chaplains reported how their own spirituality
      influenced the care they provided. SIGNIFICANCE OF RESULTS: Spiritual care in the
      VA can include a range of services and should consider the unique needs of the
      veteran population. Future studies can build upon our findings from chaplains to
      learn about the perspectives of patients, family, and other healthcare providers
      of spiritual care. This information would allow identification of strengths of
      current spiritual care practices and areas for care improvement, and ultimately
      could improve the well-being of patients at the end of life.

PMID- 22612864
TI  - Image analysis of peripheral compression artefacts of ThinPrep((r)) liquid-based
      cytology preparations.
AB  - OBJECTIVE: ThinPrep (TP), one of the Food and Drug Administration-approved liquid
      based cytology (LBC) preparations, is widely used for gynaecological and non
      gynaecological cytology samples. A unique physical artefact caused by the
      compression at the periphery in TP slides has not been adequately evaluated to
      date. METHODS: We processed four established tumour cell lines (MKN28, MKN45, KG
      1 and NB4) and mononuclear cells isolated from whole blood over Ficoll-Plaque for
      TP preparations. For this part of the study, we included five normal cervical LBC
      preparations. We then auto-counted and auto-measured the area, mean grey value
      and Feret's diameter in both the inner disc and peripheral rim of the
      preparations by image morphometry. In addition, we compared the distribution of
      atypical cell groups in the peripheral rim and inner disc of 132 lung aspirates,
      80 thyroid aspirates, 212 cerebrospinal fluids (CSFs) and 50 gynaecological
      samples. RESULTS: The areas and Feret's diameters of the cytoplasm in the
      peripheral compressed rim area were statistically larger than those of cells in
      the inner disc. The mean grey values of cells (cytoplasm and nucleus) in the
      peripheral compression rim were also smaller than those in the inner disc cells,
      leading to decreases in nuclear and cytoplasmic chromatism. Except for the mean
      grey values, the differences were not significant in the cervical samples.
      CONCLUSIONS: Cellular morphology may be markedly distorted in the peripheral rim,
      regardless of cell malignancy, which may lead to the misinterpretation of cells
      during the screening. Accordingly, cytological diagnosis based on the findings
      within the peripheral rim should take this phenomenon into account. Compressed
      cells found in the peripheral rim should be interpreted with caution when TP
      slides are used for cytopathological diagnosis.

PMID- 22612865
TI  - Different from renal artery only clamping, artery and vein clamping causes a
      significant reduction in number of rat glomeruli during warm ischemia.
AB  - PURPOSE: To evaluate glomerular injury in the rat model during renal warm
      ischemia (WI), comparing artery and vein (AV) clamping with artery only (AO)
      clamping. MATERIALS AND METHODS: Twenty-four adult male rats underwent 60 minutes
      of renal WI in the left kidney. The animals were divided into three groups: AV
      clamping, AO clamping, and Sham surgery. After 30 days, the animals were
      euthanized, and both kidneys were processed for paraffin embedding and stained
      with hematoxylin and eosin. Glomerular volume density (Vv[glom]), mean glomerular
      volume (MGV), and number of glomeruli per mm(3) (Nv[glom]) were evaluated in the
      renal cortex. RESULTS: The Vv[glom] was reduced in the left kidney (ischemic)
      when compared with the right kidney in both AV and AO groups by 11.1% and 35.4%,
      respectively; however, the difference was significant only in the AV group. The
      Nv[glom] was reduced in the left kidney when compared with the right kidney in
      both AV and AO groups by 11.6% and 31.4%, respectively; nevertheless, the
      difference was significant only in the AV group. The MGV of left and right
      kidneys was the same in both Sham and AO groups and was diminished by 6.7% in the
      AV group-not significant. CONCLUSION: AV clamping causes a significant decrease
      in the number of glomeruli in the rat model, while AO clamping reduces the
      glomerular number, but not significantly. To minimize renal injury, AO clamping
      may be preferred over AV clamping when WI is necessary in patients with
      previously compromised renal function.

PMID- 22612866
TI  - Protein-ligand crystal structures can guide the design of selective inhibitors of
      the FGFR tyrosine kinase.
AB  - The design of compounds that selectively inhibit a single kinase is a significant
      challenge, particularly for compounds that bind to the ATP site. We describe here
      how protein-ligand crystal structure information was able both to rationalize
      observed selectivity and to guide the design of more selective compounds.
      Inhibition data from enzyme and cellular screens and the crystal structures of a
      range of ligands tested during the process of identifying selective inhibitors of
      FGFR provide a step-by-step illustration of the process. Steric effects were
      exploited by increasing the size of ligands in specific regions in such a way as
      to be tolerated in the primary target and not in other related kinases. Kinases
      are an excellent target class to exploit such approaches because of the conserved
      fold and small side chain mobility of the active form.

PMID- 22612867
TI  - Effects of the head lift exercise on the swallow function: a systematic review.
AB  - OBJECTIVE: Ageing is associated with modifications in upper oesophageal sphincter
      function that may be deleterious to deglutition. The head lift exercise (Shaker
      exercise) is a head-raising work out aiming to improve the opening of this
      segment, and ultimately to reduce aspiration. We aimed to review critically the
      evidence on the effects of this structured intervention programme and to identify
      gaps to be filled by future research. MATERIAL AND METHODS: We identified
      published reports addressing the effect of this exercise in increasing the
      anteroposterior diameter and cross-sectional area of the deglutitive upper
      oesophageal sphincter opening or dysphagic symptoms. RESULTS: Nine
      methodologically heterogeneous studies were included in the review, and the
      reported effects of the head lift exercise were an increase in the anterior
      excursion of the larynx and in the anteroposterior diameter of the upper
      oesophageal sphincter opening, and the elimination of dysphagic symptoms.
      CONCLUSION: Further studies including control groups and accounting for potential
      confounders are needed for a sound assessment of the effectiveness of this
      technique. The data on the functional results are, however, promising for
      dysphagia interventions.

PMID- 22612861
TI  - Fueling and imaging brain activation.
AB  - Metabolic signals are used for imaging and spectroscopic studies of brain
      function and disease and to elucidate the cellular basis of neuroenergetics. The
      major fuel for activated neurons and the models for neuron-astrocyte interactions
      have been controversial because discordant results are obtained in different
      experimental systems, some of which do not correspond to adult brain. In rats,
      the infrastructure to support the high energetic demands of adult brain is
      acquired during postnatal development and matures after weaning. The brain's
      capacity to supply and metabolize glucose and oxygen exceeds demand over a wide
      range of rates, and the hyperaemic response to functional activation is rapid.
      Oxidative metabolism provides most ATP, but glycolysis is frequently
      preferentially up-regulated during activation. Underestimation of glucose
      utilization rates with labelled glucose arises from increased lactate production,
      lactate diffusion via transporters and astrocytic gap junctions, and lactate
      release to blood and perivascular drainage. Increased pentose shunt pathway flux
      also causes label loss from C1 of glucose. Glucose analogues are used to assay
      cellular activities, but interpretation of results is uncertain due to
      insufficient characterization of transport and phosphorylation kinetics. Brain
      activation in subjects with low blood-lactate levels causes a brain-to-blood
      lactate gradient, with rapid lactate release. In contrast, lactate flooding of
      brain during physical activity or infusion provides an opportunistic,
      supplemental fuel. Available evidence indicates that lactate shuttling coupled to
      its local oxidation during activation is a small fraction of glucose oxidation.
      Developmental, experimental, and physiological context is critical for
      interpretation of metabolic studies in terms of theoretical models. 

PMID- 22612868
TI  - Ultrafast infrared spectral fingerprints of vitamin B12 and related cobalamins.
AB  - Vitamin B(12) (cyanocobalamin, CNCbl) and its derivatives are structurally
      complex and functionally diverse biomolecules. The excited state and radical pair
      reaction dynamics that follow their photoexcitation have been previously studied
      in detail using UV-visible techniques. Similar time-resolved infrared (TRIR) data
      are limited, however. Herein we present TRIR difference spectra in the 1300-1700
      cm(-1) region between 2 ps and 2 ns for adenosylcobalamin (AdoCbl),
      methylcobalamin (MeCbl), CNCbl, and hydroxocobalamin (OHCbl). The spectral
      profiles of all four cobalamins are complex, with broad similarities that suggest
      the vibrational excited states are related, but with a number of identifiable
      variations. The majority of the signals from AdoCbl and MeCbl decay with kinetics
      similar to those reported in the literature from UV-visible studies. However,
      there are regions of rapid (<10 ps) vibrational relaxation (peak shifts to higher
      frequencies from 1551, 1442, and 1337 cm(-1)) that are more pronounced in AdoCbl
      than in MeCbl. The AdoCbl data also exhibit more substantial changes in the amide
      I region and a number of more gradual peak shifts elsewhere (e.g., from 1549 to
      1563 cm(-1)), which are not apparent in the MeCbl data. We attribute these
      differences to interactions between the bulky adenosyl and the corrin ring after
      photoexcitation and during radical pair recombination, respectively. Although
      spectrally similar to the initial excited state, the long-lived metal-to-ligand
      charge transfer state of MeCbl is clearly resolved in the kinetic analysis. The
      excited states of CNCbl and OHCbl relax to the ground state within 40 ps with few
      significant peak shifts, suggesting little or no homolysis of the bond between
      the Co and the upper axial ligand. Difference spectra from density functional
      theory calculations (where spectra from simplified cobalamins with an upper axial
      methyl were subtracted from those without) show qualitative agreement with the
      experimental data. They imply the excited state intermediates in the TRIR
      difference spectra resemble the dissociated states vibrationally (the cobalamin
      with the upper axial ligand missing) relative to the ground state with a methyl
      in this position. They also indicate that most of the TRIR signals arise from
      vibrations involving some degree of motion in the corrin ring. Such coupling of
      motions throughout the ring makes specific peak assignments neither trivial nor
      always meaningful, suggesting our data should be regarded as IR spectral
      fingerprints.

PMID- 22612873
TI  - An Invitation to Create Books and Monographs on Frontier Developments in
      Biological Structure, Dynamics, Interactions & Expression.

PMID- 22612869
TI  - Aerosol delivery during high frequency jet ventilation: an MRI evaluation.
AB  - BACKGROUND: We have previously demonstrated aerosol delivery during conventional
      and high frequency oscillatory (HFOV) ventilation using magnetic resonance
      imaging (MRI) in piglets. There are no reports on aerosol delivery during high
      frequency jet ventilation (HFJV). OBJECTIVE: To  compare delivery of aerosolized
      gadopentetate dimeglumine (Gd-DTPA) in 3 neonatal ventilator circuits:
      conventional mechanical ventilation, HFOV, and HFJV. METHODS: Aerosols of Gd-DTPA
      (0.025 mol/L) generated using a jet nebulizer placed in the inspiratory limb of
      each ventilator were delivered  into an in vitro lung model simultaneously. Multi
      slice T1-weighted spin-echo sequence scans were obtained prior to and after 10
      and 20 min of cumulative aerosol delivery. Gd-DTPA concentration was calculated
      from signal intensity changes, and the total amount of Gd-DTPA was estimated.
      RESULTS: Gd-DTPA was visualized in the lung model at 10 and 20 min for all 3
      ventilators. Gd-DTPA delivery was highest with conventional mechanical
      ventilation (1.92 MUmol at 10 min, 2.89 MUmol at 20 min), followed by HFJV (1.59
      MUmol at 10 min, 1.98 MUmol at 20 min) and HFOV (0.79 MUmol  at 10 min, 1.00
      MUmol at 20 min). CONCLUSIONS: This is the first report of effective aerosol
      delivery in a neonatal HFJV circuit. Future studies are needed for more accurate
      quantification of aerosol deposition.

PMID- 22612874
TI  - The innateness of platelets.

PMID- 22612875
TI  - Effect of hydrophilic polymers on isradipine complexation with hydroxypropyl beta
      cyclodextrin.
AB  - Complexation of isradipine with hydroxypropyl beta-cyclodextrin (HPbetaCD) in the
      presence and absence of 3 hydrophilic polymers-polyvinyl pyrrolidone (PVP),
      hydroxypropyl methylcellulose (HPMC), and polyethylene glycol (PEG)-was
      investigated with an objective of evaluating the effect of hydrophilic polymers
      on the complexation and solubilizing efficiencies of HPbetaCD and on the
      dissolution rate of isradipine from the HPbetaCD complexes. The phase solubility
      studies indicated the formation of isradipine-HPbetaCD inclusion complexes at a
      1:1M ratio in solution in both the presence and the absence of hydrophilic
      polymers. The complexes formed were quite stable. Addition of hydrophilic
      polymers markedly improved the complexation and solubilizing efficiencies of
      HPbetaCD. Solid inclusion complexes of isradipine-HPbetaCD were prepared in 1:1
      and 1:2 ratios by the kneading method, with and without the addition of
      hydrophilic polymers. The solubility and dissolution rate of isradipine were
      significantly improved by complexation with HPbetaCD. The isradipine-HPbetaCD
      (1:2) inclusion complex yielded a 9.66-fold increase in the dissolution rate of
      isradipine. The addition of hydrophilic polymers also markedly improved the
      dissolution rate of isradipine from HPbetaCD complexes: a 11.72-, 17.01-, and
      39.23-fold increase was observed with PVP, PEG, and HPMC respectively. X-ray
      diffractometry and differential scanning calorimetry indicated stronger drug
      amorphization and entrapment in HPbetaCD because of the combined action of
      HPbetaCD and the hydrophilic polymers.

PMID- 22612876
TI  - Magnetic spheres as foreign body into the bladder.
AB  - INTRODUCTION: A great variety of foreign bodies in the lower urinary tract have
      been described; many of them are self-inflicted by the patient with masturbatory
      purposes. Depending on the nature of the foreign body the diagnostic and
      management might be challenging. AIMS: We report a case of an unusual magnetic
      self-inserted foreign body into the bladder for autoerotism and briefly discuss
      the diagnostic and therapeutic implications in this challenging situation.
      METHODS: We describe all the steps we have used to adequately diagnose the
      problem, describe the foreign body and treatments for the patient. Related
      articles were found by utilizing the PubMed database and are summarized in this
      study. RESULTS:   The management approach must be planned according to the nature
      of the foreign body and should minimize bladder and urethral trauma. However,
      most of cases can be managed endoscopically. CONCLUSION: Removal of magnetic
      foreign body may be quite challenging, requiring high-level surgical skills and
      minimally invasive techniques resulting in fast recovery and low complication
      rate.

PMID- 22612877
TI  - Liposarcoma Cells with Aldefluor and CD133 Activity have a Cancer Stem Cell
      Potential.
AB  - Aldehyde dehydrogenase (ALDH) has recently been shown to be a marker of cancer
      stem-like cells (CSCs) across tumour types. The primary goals of this study were
      to investigate whether ALDH is expressed in liposarcomas, and whether CSCs can be
      identified in the ALDHhigh subpopulation. We have demonstrated that ALDH is
      indeed expressed in 10 out of 10 liposarcoma patient samples. Using a liposarcoma
      xenograft model, we have identified a small population of cells with an inducible
      stem cell potential, expressing both ALDH and CD133 following culturing in stem
      cell medium. This potential CSC population, which makes up for 0,1-1,7 % of the
      cells, displayed increased self-renewing abilities and increased tumourigenicity,
      giving tumours in vivo from as few as 100 injected cells.

PMID- 22612878
TI  - Biochemical and growth acclimation of birch to night temperatures: genotypic
      similarities and differences.
AB  - The responses of plants to environmental factors are connected to the time of
      day. In this study, silver birch (Betula pendula) was grown in growth chambers at
      five different night temperatures (6-22  degrees C), using gradual changes during
      the evening and morning hours. Despite the increased night respiration and
      unaffected daytime net photosynthesis (per square metre), the carbon uptake
      (biomass) of birch did not decrease, probably due to enhanced biochemical
      processes on warmer nights and the advantage of higher temperatures during the
      evening and morning hours. The plant stem height, internode length, stem dry
      weight (DW), stem mass fraction and specific leaf area increased with warmer
      night temperatures. Changes in growth and metabolite concentrations were partly
      nonlinear along the temperature gradient. Thus, the temperature effect depends on
      the temperature window considered. Genotypes had both common and genotype
      specific biochemical responses to night temperatures. The common responses among
      genotypes were related to growth responses, whereas the unique responses may
      indicate genotype-specific differences in acclimation. The differences in
      genotypic growth and metabolite levels are valuable for assessing genotype
      qualities and understanding the connections between the metabolome and growth.

PMID- 22612879
TI  - Transfusion of cryopreserved human red blood cells into healthy humans is
      associated with rapid extravascular hemolysis without a proinflammatory cytokine
      response.
AB  - BACKGROUND: Transfusion of stored red blood cells (RBCs) can be associated with
      adverse side effects. Recent studies in mice transfused with stored RBCs showed
      that a strong proinflammatory cytokine storm was induced due to extravascular
      hemolysis already at 2 hours after transfusion. Therefore, we here investigated
      if transfusion of 2 units of cryopreserved autologous RBCs induced a
      proinflammatory response in healthy human volunteers. STUDY DESIGN AND METHODS:
      Two units of autologous RBCs, cryopreserved for 16 weeks, were transfused into 10
      healthy human volunteers. Serum and blood samples taken at 2 hours before and at
      2 and 48 hours after transfusion were analyzed for signs of extravascular
      hemolysis and the presence of proinflammatory cytokines. RESULTS: At 2 hours
      after transfusion, transferin-bound serum iron, as well as transferin saturation
      and total bilirubin, were already significantly increased. These measures all
      returned back toward that in pretransfusion samples at 48 hours after
      transfusion. No increases in the production of the proinflammatory cytokines
      interleukin (IL)-1beta, IL-6, IL-8, monocyte chemotactic protein-1, macrophage
      inflammatory protein-1beta, or tumor necrosis factor-alpha were detected at any
      time point after transfusion. CONCLUSION: Although a significant level of
      extravascular hemolysis already occurred at 2 hours after transfusion of
      cryopreserved RBCs, there were no signs of proinflammatory cytokine production up
      to 48 hours after transfusion.

PMID- 22612880
TI  - The changes in female physical and childbearing characteristics in China and
      potential association with risk of breast cancer.
AB  - BACKGROUND: There has been a sharp increase in the incidence of breast cancer in
      China in recent years. A number of female physical characteristics, such as age
      at menarche, menopause, first birth and the duration of breastfeeding, have been
      linked to breast cancer, yet data on these factors in Chinese women is largely
      missing both for aggregate and age-specific data. Thus, the objective of this
      study was to explore changes in female menstrual and childbearing characteristics
      as a possible explanation for increasing rates of breast cancer in this country.
      METHOD: From July to September 2008, a population based cross-sectional breast
      cancer survey covering 124,758 females from 4 provinces or cities in Eastern
      China was carried out, using multi-stage and cluster methods. In-person
      interviews based on a self-designed structured questionnaire were performed, in
      which female physiological and reproductive factors, such as age at menarche and
      menopause, menstrual cycle history, childbearing history, breastfeeding methods,
      abortions or miscarriage, were included. For every 10-year age category, the
      subjects were divided, and across those age groups, all the above factors were
      compared respectively and changes in physical and childbearing characteristics
      were evaluated. ANOVA was used to compare the differences across the groups.
      RESULTS: A total of 122058 subjects were included in the final analysis. The mean
      age at menarche was 15.39 years, the mean number of full-term pregnancies was
      1.58, the mean duration of breastfeeding was 22.68 months, the mean age at first
      birth was 23.75 years, the mean frequency of miscarriage was 0.36, and the mean
      age at menopause was 48.63 years. Significant differences across the several age
      groups were noted for the age at menarche, number of full-term pregnancies,
      accumulated duration of breastfeeding, age at first birth, number of
      miscarriages, and age at menopause. These data clearly showed a gradual shift
      towards an earlier age at menarche, fewer pregnancies and shorter breastfeeding
      lengths. CONCLUSIONS: Significant changes in female physical and childbearing
      characteristics across a number of different age ranges were detected. These
      changes may be related to the increasing trend of breast cancer in China.

PMID- 22612882
TI  - Meaningful and useful measures of performance: the patient's perspective.

PMID- 22612883
TI  - Strong foundations offer towering opportunities and endless possibilities.

PMID- 22612884
TI  - Perioperative music or headsets to decrease anxiety.
AB  - The ambient noise of monitors, other patients, and staff in the postanesthesia
      care unit/operating room may elevate levels of anxiety. The purpose of our study
      was to determine the effect of music versus noise-blocking headphones on the
      level of anxiety in women undergoing gynecologic same-day surgery. Institutional
      Review Board approval was obtained. The women were approached for consent and
      randomized to usual care, music with headphones, or headphones only. Preoperative
      and postoperative anxiety was rated on a scale of 0 to 10. Music/headphones were
      continued throughout surgery and removed when Aldrete level of consciousness
      equaled 2. The 119 women had a mean age of 38.8 (standard deviation=2.2) years.
      Of interest, 51 (45%) reported very low preoperative anxiety (0-3/10) and were
      excluded. All groups experienced a drop in anxiety from pre- to postoperative
      status, but the usual care group had the least improvement (P<.05). The music
      group experienced the lowest postoperative anxiety scores; the headphone group
      had a greater change overall. Music is a relatively inexpensive intervention,
      easy to administer, and noninvasive.

PMID- 22612881
TI  - The problem with "problem behaviors": a systematic review of the association
      between individual patient behavioral and psychological symptoms and caregiver
      depression and burden within the dementia patient-caregiver dyad.
AB  - BACKGROUND: Behavioral and psychological symptoms of dementia (BPSDs) are
      routinely cited as important predictors of caregiver burden and depression.
      Although BPSDs include a wide variety of patient behaviors, they are routinely
      grouped together as one construct to differentiate them from cognitive symptoms
      of dementia. Determining the specific BPSDs that result in increased depression
      and burden for caregivers may elucidate the stress process for caregivers and
      facilitate the development of effective interventions for caregivers. METHODS: We
      conducted a systematic review of English-language articles published from 1990 to
      2010 to determine whether there are known symptoms or symptom clusters which
      exert undue negative impact on caregiver depression and burden. Additionally, we
      review systems used for classifying BSPD symptom clusters and determine whether
      there have been any mechanisms studied by which individual BPSD symptoms
      negatively affect caregivers. Finally, we examine how the role of timing of
      symptoms has been examined within the literature. RESULTS: Thirty-five original
      research articles examined the impact of an individual behavior symptom on
      caregiver burden or depression/depressive symptoms. The studies had no consistent
      system for categorizing symptoms. Although depression, aggression, and sleep
      disturbances were the most frequently identified patient symptoms to impact
      negatively on caregivers, a wide range of symptoms was associated with caregiver
      burden and depression. CONCLUSIONS: The evidence is not conclusive as to whether
      some symptoms are more important than others. The studies reviewed were largely
      exploratory relative to the differential impact of individual BPSDs and did not
      focus on testing causal mechanisms by which specific symptoms exert more impact
      on caregiver mental health than others. Future research may benefit from the re
      conceptualization of BPSDs from the perspective of their impact on the caregiver
      to examine hypothesis-driven differences among BPSD symptom clusters.

PMID- 22612885
TI  - "Is that my leg?" patients' experiences of being awake during regional anesthesia
      and surgery.
AB  - Most knee or hip replacement surgery is performed under regional anesthesia, when
      patients are awake. Previous research has primarily focused on patients'
      experiences during general anesthesia. The aim of this study was to uncover the
      meaning of being awake during regional anesthesia and surgery. Nine interviews
      with patients undergoing knee or hip replacement surgery comprise the data. The
      phenomenological analysis shows that being awake during surgery can be compared
      with walking a tightrope because of ambiguous feelings. Four interrelated
      constituents further elucidated the patients' experiences: balancing between
      proximity and distance in the operating theater, balancing between having control
      and being left out, my partly inaccessible body handled by others, and the
      significant role of the carer. Anesthesia providers and perioperative nurses need
      to understand the awake patients' intraoperative experiences to support and
      confirm them when they can no longer experience or have full access to their
      body.

PMID- 22612886
TI  - Unplanned perioperative hypothermia and agreement between oral, temporal artery,
      and bladder temperatures in adult major surgery patients.
AB  - Accurate body core temperature measurement is essential in perioperative areas to
      quickly recognize and address abnormal temperatures. The purposes of this
      prospective, descriptive study were to accurately identify unplanned
      perioperative hypothermia (UPH) in 64 elective major surgery patients; to
      describe factors that increased the risk of UPH; to describe active/passive
      warming measures; to describe thermal comfort in patients with and without UPH;
      and to compare oral, temporal artery, and bladder temperatures. Based on bladder
      temperatures, 52% of the patients had UPH in the operating room (OR) and 42% on
      postanesthesia care unit (PACU) admission. The temporal artery thermometer did
      not detect any hypothermia. Descriptive data and Bland-Altman plots showed lack
      of agreement between the temporal artery thermometer readings and those of the
      oral and bladder thermometers. The patient's thermal comfort report did not
      accurately reflect hypothermia. Factors found to increase the risk of UPH
      included older age, BMI lower than 30, and OR ambient temperature lower than 68
      degrees F. All but one patient had active warming in the OR; active warming was
      infrequently used in the PACU. Based on our findings and findings in previous
      studies, we do not recommend using the temporal artery thermometer in
      perioperative areas. To prevent UPH, we recommend aggressive use of convective
      and conductive warming measures in perioperative areas and increasing OR ambient
      temperatures.

PMID- 22612887
TI  - A quasi-experimental study examining the safety profile and comfort provided by
      two different blanket temperatures.
AB  - Surgical patients are often covered with warm blankets to alleviate the
      discomfort of feeling too cold in the perioperative environment. The goal of this
      study was to provide evidence to guide institutional blanket warming policies by
      examining blanket thermal behavior and blanket temperature preference of
      postoperative patients. The hypothesis was that 155 degrees F blankets are safe
      for patient use and provide a higher level of thermal comfort to perioperative
      patients than do 110 degrees F blankets. A sample of 156 adult participants was
      randomized to the intervention group (n=76), who received 155 degrees F blankets,
      or the control group (n=80), who received 110 degrees F blankets. Participants
      were covered neck to toe with the blankets in the postanesthesia care unit, and
      measurements were obtained for 10 minutes. An infrared thermometer was used to
      measure skin and blanket temperatures, and a numeric scale was used to measure
      thermal comfort. Blanket cooling rates were examined along with the effect of
      blanket temperatures on participants' skin temperature, oral temperature, and
      thermal comfort rating. Mean blanket temperatures for both groups were less than
      93 degrees F two minutes after application. The intervention group showed higher
      skin temperatures and thermal comfort throughout 10 minutes of data collection.
      The results of this study support the hypothesis that it is safe to cover
      surgical patients with 155 degrees F blankets. Results also indicate a
      correlation between 155 degrees F blankets and higher skin temperature and
      thermal comfort.

PMID- 22612888
TI  - Evidence into practice: publishing an evidence-based practice project.

PMID- 22612889
TI  - Write the wrong: narrative documentation.

PMID- 22612890
TI  - Opioid-induced sedation and respiratory depression: evidence-based monitoring
      guidelines.

PMID- 22612891
TI  - Social networking: possible risks to nurses.

PMID- 22612892
TI  - Communication, children, and cortisol.

PMID- 22612893
TI  - The expert and the novice: a tale of two authors.

PMID- 22612894
TI  - Self-care and humor.

PMID- 22612895
TI  - Susceptibility and lack of evidence for a viremic state of rabies in the night
      owl monkey, Aotus nancymaae.
AB  - BACKGROUND: Rabies causes an acute fatal encephalomyelitis in most mammals
      following infection with rhabdovirus of the genus Lyssavirus. Little is known
      about rabies virus infection in species of New World non-human Primates (NHP). To
      investigate the suitability of the owl monkey Aotus nancymaae asissue sections
      examined were unremarkable for inflammation or other histologic signs of rabies a
      viable animal model for rabies virus candidate vaccine testing, we used clinical
      presentation, serology, viral isolation, and PCR to evaluate the incubation
      period, immunity, and pathogenesis of infected animals. We tested the hypothesis
      that no viremic state exists for rabies virus. METHODS: Eight monkeys divided
      into two equal groups were inoculated intramuscularly either in the neck or
      footpad with 105 pfu of rabies virus (Pasteur/V-13R) and observed for >130 days.
      Oral and blood samples were collected and analyzed. RESULTS: Two monkeys
      inoculated in the neck displayed classic paralytic rabies. The mean incubation
      period was 11.5 days. The average maximum IgG response (antibody titer >0.200
      O.D.) was achieved at day 10.0 and 62.3 in the clinical rabies and non-clinical
      rabies cases, respectively (p = 0.0429). No difference in IgM or IgG time to
      seroconversion or average maximum IgM level was observed between neck versus
      footpad inoculation groups. No viremia or viral shedding was detected by PCR or
      viral isolation during the observation period, including within the two
      symptomatic animals three days after disease onset. Tissue sections examined were
      unremarkable for inflammation or other histologic signs of rabies within the
      asymptomatic animal. Similarly none of the brain sections exhibited
      immunoreactivity for rabies virus antibody. DISCUSSION: This study demonstrates
      there is no difference in time to immune response between inoculation sites and
      distance to the brain; however, immune response tends to be more rapid in cases
      of clinically apparent disease and prolonged in cases infected at sites further
      from the brain. CONCLUSIONS: Our findings support the hypothesis that a viremic
      state for rabies does not exist in the New World Monkey, Aotus nancymaae, and it
      appears that this species may be refractory to infection. The species does
      provide a suitable model to assess post infection immune responses. Additional
      studies that address the limitations of sample size, length of observation, and
      lack of measurable infection should be conducted.

PMID- 22612896
TI  - Enhanced transmural dispersion of repolarization in patients with J wave
      syndromes.
AB  - INTRODUCTION: Recently, great attention has been paid to the risk stratification
      of asymptomatic patients with an electrocardiographic early repolarization (ER)
      pattern. We investigated several repolarization parameters including the Tpeak
      Tend interval and Tpeak-Tend/QT ratio in healthy individuals and patients with J
      wave syndrome who were aborted from sudden cardiac death. METHODS AND RESULTS:
      Ninety-two subjects were enrolled: 12 patients with ventricular fibrillation
      associated with J waves, 40 healthy subjects with an uneventful ER pattern and 40
      healthy control subjects (C) without any evident J waves. Using ambulatory
      electrocardiogram recordings, the average QT interval, corrected QT interval
      (QTc), Tpeak-Tend (Tp-e) interval, which is the interval from the peak to the end
      of the T wave, and Tp-e/QT ratio were calculated. Using ANOVA and post hoc
      analysis, there was no significant difference in the average QT and QTc in all 3
      groups (QT; 396 +/- 27 vs 405 +/- 27 vs 403 +/- 27 m, QTc; 420 +/- 26 vs 421 +/-
      21 vs 403 +/- 19 milliseconds in the C, ER pattern and J groups, respectively).
      The Tp-e interval and Tp-e/QT ratio were significantly more increased in the J
      wave group than the ER Pattern group (Tp-e: 86.7 +/- 14 milliseconds vs 68 +/-
      13.2 milliseconds, P < 0.001, Tp-e/QT; 0.209 +/- 0.04 vs 0.171 +/- 0.03, P <
      0.001), but they did not significantly differ between the C and ER pattern groups
      (Tp-e: 68.6 +/- 7.5 vs 68 +/- 13.2, P = 0.97, Tp-e/QT 0.174 +/- 0.02 vs 0.171 +/-
      0.03, P = 0.4). CONCLUSION: As novel markers of heterogeneity of ventricular
      repolarization, Tpeak-Tend interval and Tp-Te/QT ratio are significantly
      increased in patients with J wave syndromes compared to age and sex-matched
      uneventful ER.

PMID- 22612897
TI  - Mindfulness and psychosocial care in cancer: historical context and review of
      current and potential applications.
AB  - Mindfulness-based interventions and mindfulness techniques have become
      increasingly popular in psychosocial care.  These interventions have also been
      increasingly used with cancer patients and survivors. However, more attention is
      due to issues such as how these techniques may be specifically relevant for an
      oncology population and whether the religious derivation of mindfulness should be
      considered by frontline psychosocial clinicians. This article provides a history
      and overview of the use of mindfulness in psychosocial cancer care. 

PMID- 22612899
TI  - Knowledge and barriers associated with assessment and treatment for hepatitis C
      virus infection among people who inject drugs.
AB  - INTRODUCTION AND AIMS: Uptake of treatment for hepatitis C virus (HCV) infection
      among people who inject drugs is low. Further understanding is required of the
      relationship between HCV knowledge and treatment willingness, assessment and
      treatment in this population. DESIGN AND METHODS: A cross-sectional self
      administered survey was conducted with clients of four opioid substitution
      therapy (OST) clinics and the Medically Supervised Injecting Centre in Sydney,
      Australia. RESULTS: Of 132 participants, 85 (64%) self-reported having HCV
      infection. HCV knowledge was mixed (mean 6.5, range 0-12) and was relatively
      lower on items measuring knowledge of factors impacting HCV-related disease
      progression. The likelihood of being in a higher knowledge category was
      associated with being female [adjusted odds ratio (AOR) = 3.78, 95% confidence
      interval (CI) (1.79, 7.98)], higher formal education [AOR = 3.28, 95% CI (1.57,
      6.88)], being on a current OST program [AOR = 2.61, 95% CI (1.10, 6.19)] and
      being older [AOR = 1.04, 95% CI (1.01, 1.09)]. Participants receiving OST were
      more likely to report higher willingness to have HCV treatment [OR = 4.45, 95% CI
      (2.23, 8.17)]. Having been assessed for HCV treatment was associated with younger
      age [AOR = 0.93; CI 95% (0.88, 1.00)] and higher formal education [AOR = 7.81;
      95% CI (1.62, 37.71)]. DISCUSSION AND CONCLUSIONS: Overall, knowledge scores were
      mid-range. Knowledge of modifiable factors influencing HCV-related liver disease
      progression was particularly low indicating the need for ongoing education.
      Education should also be targeted at older people and those not on OST, and be
      inclusive of those with lower literacy levels.

PMID- 22612898
TI  - Female sexual dysfunction among young and middle-aged women in Hong Kong:
      prevalence and risk factors.
AB  - INTRODUCTION: Sexual dysfunction is a serious public health problem that affects
      women's quality of life. However, there is very little epidemiological data on
      its incidence in Hong Kong Chinese women. AIM: To estimate the prevalence of, and
      risk factors associated with sexual dysfunction among young and middle-aged women
      in Hong Kong. METHODS: The study was part of the ninth Knowledge, Attitude, and
      Practice survey conducted by the Family Planning Association of Hong Kong in
      2007. The dataset comprised 1,510 face-to-face interviews with Hong Kong Chinese
      women aged 19-49 living in the community. MAIN OUTCOME MEASURE: The Diagnostic
      and Statistical Manual of Mental Disorders, Fourth Edition classification of
      sexual dysfunction was used to measure female sexual dysfunction (FSD). RESULTS:
      At least one form of FSD was reported by 37.9% of the sample. Multivariate
      analysis showed that having sought medical help for sexual problems (odds ratio
      [OR] = 4.20), having a partner with erectile dysfunction (OR = 2.44) and
      premature ejaculation (OR = 2.56), perceiving sex as unimportant to marriage (OR
      = 1.57), and reporting marital dissatisfaction (OR = 1.45) were all significant
      risk factors for FSD and its specific components among the sample. However,
      having liberal attitudes to sex (OR = 0.63) was a protective factor. CONCLUSION:
      The prevalence of FSD is lower among Hong Kong Chinese young and middle-aged
      women than in the United States and some Asian countries. Factors contributing to
      the risk of FSD span the domains of sexual experience, attitudes to sex, and
      relationship factors. These findings suggest future directions for the delivery
      of services addressing the prevention and treatment of FSD.

PMID- 22612900
TI  - Fusidic acid for the treatment of bone and joint infections caused by meticillin
      resistant Staphylococcus aureus.
AB  - There is a lack of surveillance data on resistance to fusidic acid (FA) in Asia,
      and no reviews of FA usage for the treatment of orthopaedic infections have been
      conducted since the year 2000. In this study, we present a systemic literature
      review of FA resistance in Asia and the clinical use of FA for the treatment of
      bone and joint infections (BJIs). The in vitro activity of FA against meticillin
      resistant Staphylococcus aureus (MRSA) isolates remains good, with low (<10%)
      resistance rates in most Asian countries. FA in Asia appears to be a better oral
      anti-MRSA agent than trimethoprim/sulfamethoxazole and clindamycin. More than 80
      cases of FA use for BJI have been reported since 2000 and the recurrence or
      failure rate is <10%. There is much evidence supporting the use of FA in
      combination with other antibiotics (e.g. rifampicin) as an oral treatment
      following intravenous glycopeptide treatment for BJIs.

PMID- 22612902
TI  - Vaginal metastasis of a Ewing Sarcoma five years after resection of the primary
      tumor.
AB  - A 35-year-old female presented with pain and swelling of the left wrist. A
      diagnosis of Ewing sarcoma was made and she underwent neoadjuvant chemotherapy
      and surgery.   Macroscopic viable areas remained on the map of the surgical
      specimen; as such, she was classified as a poor responder and received high dose
      adjuvant chemotherapy.  She remained disease-free for five years, until age 40. A
      vaginal polyp   was then detected during a routine gynaecologic examination.  It
      was removed and histopathology revealed metastatic Ewing sarcoma. To our
      knowledge, this is  the first reported case  of a vaginal metastasis of  Ewing
      sarcoma.

PMID- 22612901
TI  - Genetic diversity analyses of antimicrobial resistance genes in clinical
      Chryseobacterium meningosepticum isolated from Hefei, China.

PMID- 22612903
TI  - Eosinophilic dermatosis of hematologic malignancy.
AB  - Cutaneous involvement by an eosinophil-rich process (eosinophilic dermatosis) may
      be encountered in the setting of various hematologic malignancies, including
      mantle cell lymphoma, acute monocytic leukemia, acute lymphoblastic leukemia,
      large cell lymphoma, myelofibrosis and chronic lymphocytic leukemia (CLL). Of the
      various hematologic malignancies, eosinophilic dermatosis has been most
      frequently described in association with CLL. Published previously as insect bite
      like reaction and eosinophilic dermatosis of myeloproliferative disease, this
      rare dermatitis presents as a pruritic, papular and occasionally vesicular
      eruption associated with an eosinophil-rich infiltrate histopathologically.
      Although clinical and histopathologic features are similar to insect bites,
      affected patients frequently deny a history of insect bites. We report a case of
      eosinophilic dermatosis of hematologic malignancy in a patient with known history
      of CLL.

PMID- 22612904
TI  - Pharmacodynamic effect of clopidogrel therapy and switching to cilostazol in
      patients with the CYP2C19 loss-of-function allele (ACCEL-SWITCH) study.

PMID- 22612905
TI  - Cytotoxic effects of denture adhesives on primary human oral keratinocytes,
      fibroblasts and permanent L929 cell lines.
AB  - BACKGROUND: To date, there have been very little data on the cytotoxic responses
      of different cell lines to denture adhesives. OBJECTIVE: To determine the
      cytotoxicity of three denture adhesives on primary human oral keratinocytes
      (HOKs), fibroblasts (HOFs) and permanent mouse fibroblasts cell lines (L929).
      METHODS: Three commercial denture adhesives (two creams and one powder) were
      prepared for indirect contact using the agar diffusion test, as well as extracts
      in MTT assay. The results of the MTT assay were statistically analysed by one-way
      anova and Tukey's test (p < 0.05). RESULTS: All of the tested denture adhesives
      showed mild to moderate cytotoxicity to primary HOKs (p < 0.001), whereas none of
      three was toxic to L929 cells (p > 0.05) in both assays. For primary HOFs
      cultures, slight cytotoxicity was observed for one of the products from the agar
      diffusion test and undiluted eluates of all tested adhesives with MTT assay (p <
      0.01). CONCLUSION: Denture adhesives are toxic to the primary HOKs and HOFs
      cultures, whereas non-toxic to L929 cells. The results suggest that primary human
      oral mucosal cells may provide more valuable information in toxicity screening of
      denture adhesives.

PMID- 22612906
TI  - Low-dose, wide-detector array thoracic aortic CT angiography using an iterative
      reconstruction technique results in improved image quality with lower noise and
      fewer artifacts.
AB  - BACKGROUND: Iterative reconstruction techniques (IRTs) may improve image quality
      for low-dose imaging compared with filtered back projection (FBP) reconstruction.
      OBJECTIVES: We compared the results of an IRT for low-dose thoracic aortic
      computed tomography (CT) imaging with those from FBP reconstruction. METHODS:
      Data from 50 patients who underwent 256-slice CT for evaluation of the thoracic
      aorta were reconstructed with FBP and an IRT (iDose(4)) at 3 noise-reduction
      strengths (levels 2, 4, and 6). A blinded reader graded image quality (scale, 1
      5; 5 = high diagnostic confidence) and the extent of shoulder artifact (scale, 1
      5; 5 = no artifact) on all reconstructions. A second reader evaluated a subset of
      20 cases to determine interreader and intrareader reproducibility. The mean and
      SD of attenuation were measured at 5 locations along the thoracic aorta and both
      subclavian arteries. RESULTS: Image noise (SD of attenuation) improved with IRT
      relative to FBP (aorta: FBP, 31.4 +/- 8.6 HU; IRT level 2, 25.1 +/- 6.9 HU; level
      4, 21.7 +/- 6.2 HU; level 6, 17.2 +/- 5.4 HU; P < 0.0001; subclavian arteries:
      FBP, 92.7 +/- 34.6 HU; IRT level 2, 50.1 +/- 17.1 HU; level 4, 48.9 +/- 18.6 HU;
      level 6, 45.2 +/- 19.2 HU; P < 0.0001), whereas mean attenuation was unchanged.
      Increasing image quality was observed in the aorta and through the shoulders as
      the contribution from IRT to the final images increased (P < 0.0001). Significant
      differences were noted between readers in image quality assessment of the aorta
      but not through the shoulders. CONCLUSION: IRT is associated with reduced noise
      and shoulder artifact and allows for low-dose aortic CT imaging.

PMID- 22612907
TI  - On integrating experimental and theoretical models to determine physical
      mechanisms of morphogenesis.
AB  - Researchers in developmental biology are increasingly recognizing the value of
      theoretical models in studies of morphogenesis. However, creating and testing
      realistic quantitative models for morphogenetic processes can be an extremely
      challenging task. The focus of this paper is on models for the mechanics of
      morphogenesis. Models for these problems often must include large changes in
      geometry, leading to highly nonlinear problems with the possibility of multiple
      solutions that must be sorted out using experimental data. Here, we illustrate
      our approach to these problems using the specific example of head fold formation
      in the early chick embryo. The interplay between experimental and theoretical
      results is emphasized throughout, as the model is gradually refined. Some of the
      limitations inherent in theoretical/computational modeling of biological systems
      are also discussed.

PMID- 22612908
TI  - Efficacy of albendazole and moxidectin and resistance to ivermectin against
      Libyostrongylus douglassii and Libyostrongylus dentatus in ostriches.
AB  - Anthelmintic resistance has emerged globally as a problem amongst nematode of
      livestock and has been particularly well documented in equine and small
      ruminants. There are no studies regarding the efficacy of anthelmintics against
      the hematophagous nematodes in ostriches, Libyostrongylus dentatus; and just a
      few on L. douglassii. Here the efficacy of albendazole, ivermectin and moxidectin
      were evaluated against these two species in an ostrich farm in Minas Gerais
      state, Brazil. The feces were collected on the day of treatment and after 13 days
      of an oral dose of albendazole (6 mg/kg), or an injected dose (0.2mg/kg) of
      ivermectin or moxidectin. The fecal egg count reduction test and coprocultures
      were performed to determine possible resistance against the drugs used. An
      efficacy of 60% was found for ivermectin, while albendazole and moxidectin were
      100% effective. Both worm species appeared to have reduced sensitivity to
      ivermectin.

PMID- 22612910
TI  - Cognition, coping, and outcome in Parkinson's disease.
AB  - BACKGROUND: Cognitive impairment and depression are common and disabling non
      motor symptoms of Parkinson's disease (PD). Previous studies have shown
      associations between them but the nature of the relationship remains unclear. In
      chronic illness, problem- or task-oriented coping strategies are associated with
      better outcome but often require higher level cognitive functioning. The present
      study investigated, in a sample of patients with PD, the relationships between
      cognitive function, choice of coping strategies, and a broad index of outcome
      including depression, anxiety, and health-related quality of life (QoL). It was
      hypothesized that the coping strategy used could mediate the association between
      cognition and outcome. METHODS: 347 participants completed the Coping Inventory
      for Stressful Situations, the Hospital Anxiety and Depression Scale, the
      Parkinson's Disease Questionnaire-8, the Unified Parkinson's Disease Rating
      Scale, and the Addenbrooke's Cognitive Examination-Revised. Structural Equation
      Modeling was used to test the hypothesized model of cognition, coping, and
      outcome based on a direct association between cognition and outcome and an
      indirect association mediated by coping. RESULTS: Overall, poorer cognition
      predicted less use of task-oriented coping, which predicted worse outcome (a
      latent variable comprised of higher depression and anxiety and lower QoL). The
      analyses suggested a small indirect effect of cognition on outcome mediated by
      coping. CONCLUSIONS: The findings suggest that patients who fail to employ task
      oriented coping strategies may be at greater risk of depression, anxiety, and
      poor health-related QoL. Even mild to moderate cognitive impairment may
      contribute to reduced use of task-oriented coping. Suitably adapted cognitive
      behavioral approaches may be useful to enable the use of adaptive coping
      strategies in such patients.

PMID- 22612909
TI  - Molecular and cellular mechanisms of the age-dependency of opioid analgesia and
      tolerance.
AB  - The age-dependency of opioid analgesia and tolerance has been noticed in both
      clinical observation and laboratory studies. Evidence shows that many molecular
      and cellular events that play essential roles in opioid analgesia and tolerance
      are actually age-dependent. For example, the expression and functions of
      endogenous opioid peptides, multiple types of opioid receptors, G protein
      subunits that couple to opioid receptors, and regulators of G protein signaling
      (RGS proteins) change with development and age. Other signaling systems that are
      critical to opioid tolerance development, such as N-methyl-D-aspartic acid (NMDA)
      receptors, also undergo age-related changes. It is plausible that the age
      dependent expression and functions of molecules within and related to the opioid
      signaling pathways, as well as age-dependent cellular activity such as agonist
      induced opioid receptor internalization and desensitization, eventually lead to
      significant age-dependent changes in opioid analgesia and tolerance development.

PMID- 22612911
TI  - Raman and IR spectroscopic investigation of As adsorbed on Mn3O4 magnetic
      composites.
AB  - Raman and IR spectra were recorded of the As-loaded Mn(3)O(4) magnetic composites
      obtained from the adsorption studies performed with As(III). XANES results for
      the composite after As(III) removal tests show that the As adsorbed is at the
      oxidized arsenic form, As(V). Monodentate and bidentate surface complexes are
      suggested for arsenic adsorption onto the composite (5-16 mg/g). Precipitation of
      manganese arsenate is observed for high As loading (35 mg/g).

PMID- 22612912
TI  - Vignettes from a zone of conflict.

PMID- 22612913
TI  - Genetic contribution of catechol-O-methyltransferase variants in treatment
      outcome of low back pain: a prospective genetic association study.
AB  - BACKGROUND: Treatment outcome of low back pain (LBP) is associated with inter
      individual variations in pain relief and functional disability. Genetic variants
      of catechol-O-methyltransferase (COMT) gene have previously been shown to be
      associated with pain sensitivity and pain medication. This study examines the
      association between COMT polymorphisms and 7-11 year change in Oswestry
      Disability Index (ODI) and Visual Analog Score (VAS) for LBP as clinical outcome
      variables in patients treated with surgical instrumented lumbar fusion or
      cognitive intervention and exercise. METHODS: 93 unrelated patients with chronic
      LBP for duration of >1 year and lumbar disc degeneration (LDD) were treated with
      lumbar fusion (N = 60) or cognitive therapy and exercises (N = 33). Standardised
      questionnaires assessing the ODI, VAS LBP, psychological factors and use of
      analgesics, were answered by patients both at baseline and at 7-11 years follow
      up. Four SNPs in the COMT gene were successfully genotyped. Single marker as well
      as haplotype association with change in ODI and VAS LBP, were analyzed using
      Haploview, linear regression and R-package Haplostats. P-values were not formally
      corrected for multiple testing as this was an explorative study. RESULTS:
      Association analysis of individual SNPs adjusted for covariates revealed
      association of rs4633 and rs4680 with post treatment improvement in VAS LBP (p =
      0.02, mean difference (beta) = 13.5 and p = 0.02, beta = 14.2 respectively).
      SNPs, rs4633 and rs4680 were found to be genotypically similar and in strong
      linkage disequilibrium (LD). A significant association was found with covariates,
      analgesics (p = 0.001, beta = 18.6); anxiety and depression (p = 0.008, beta =
      15.4) and age (p = 0.03, mean difference per year (beta) = 0.7) at follow-up.
      There was a tendency for better improvement among heterozygous patients compared
      to the homozygous. No association was observed for the analysis of the common
      haplotypes, these SNPs were situated on. CONCLUSIONS: Results suggest an
      influence of genetic variants of COMT gene in describing the variation in pain
      after treatment for low back pain. Replication in large samples with testing for
      other pain related genes is warranted.

PMID- 22612914
TI  - Right atrial remodeling is more advanced in patients with atrial flutter than
      with atrial fibrillation.
AB  - INTRODUCTION: Atrial fibrillation (AF) and atrial flutter (AFL) are related
      arrhythmias with common triggers, yet in individual patients either AF or AFL
      often predominates. We performed detailed electrophysiologic (EP) and
      electroanatomic (EA) studies of the right atrium (RA) in patients with AF and AFL
      to determine substrate differences that may explain the preferential expression
      of AF/AFL in individual patients. METHODS: Patients with AF (n = 13) were
      compared to patients with persistent AFL (n = 10). Detailed studies were
      performed, and 3-dimensional electroanatomic mapping studies were created and the
      RA was divided into 4 segments for regional analysis. Global, septal, lateral,
      anterior, and posterior segments were compared for analysis of: bipolar voltage;
      proportion of low-voltage areas and areas of electrical silence; conduction
      times; and proportion of abnormal signals (fractionated signals and double
      potentials). RESULTS: Compared to patients with AF, patients with AFL had (1)
      lower bipolar voltage and an increase in the proportion of low-voltage areas; (2)
      an increase in the proportion of complex signals; and (3) prolongation of
      activation times. CONCLUSIONS: Patients with AFL showed more advanced remodeling
      than patients with AF with slowed conduction, lower voltage areas with regions of
      electrical silence, and a greater proportion of complex signals, particularly in
      the posterior RA. These changes facilitate the stabilization of AFL and may
      explain why some patients are more likely to develop AFL as a sustained clinical
      arrhythmia.

PMID- 22612915
TI  - Characterization of a Panela cheese with added probiotics and fava bean starch.
AB  - Of 20 Lactobacillus and 8 Bifidobacterium species examined, only Bifidobacterium
      breve ATCC 15700 was able to ferment starch from fava beans. Bifidobacterium
      breve ATCC 15700 and Lactobacillus rhamnosus GG ATCC 53103 were selected as
      probiotics for use in fresh-style Panela cheese. Two types of fresh cheese (with
      and without 3% fava bean starch) were manufactured with 3 combinations of
      probiotics: L. rhamnosus GG only, B. breve only, or both L. rhamnosus GG and B.
      breve. During 4 wk of storage at 4 degrees C, the addition of fava bean starch to
      the cheese was not found to cause significant differences in the viability of
      either probiotic strain. However, the microstructure and texture of Panela cheese
      were altered, resulting in a much softer product. A sensory panel showed that the
      presence of added fava bean starch in Panela cheese was less desirable to
      consumers, whereas probiotic supplementation had no effect on perceived taste or
      appearance. Panela cheese could be a suitable food for inclusion of probiotic
      bacteria.

PMID- 22612916
TI  - Influence of lamb rennet paste on the lipolytic and sensory profile of Murcia al
      Vino cheese.
AB  - The influence of lamb rennet paste (71.1% chymosin, 177 international milk
      clotting units/mL, 4.57U/g of lipase activity) during the ripening of Murcia al
      Vino goat cheese was studied. The aim of this study was to improve the knowledge
      of the effect of lamb rennet paste on the lipolytic patterns in this type of
      cheese by reference to the evolution of total and free fatty acids. A sensory
      analysis was carried out to compare cheeses made with commercial and paste
      rennet. The rennet paste showed higher lipolytic activity, enhancing the
      production of short-chain free fatty acids. In addition, the cheese produced with
      lamb rennet paste had a slightly more bitter and piquant taste, making it an
      attractive commercial alternative that can be used to develop new varieties of
      goat cheese.

PMID- 22612918
TI  - A cheese-containing diet modulates immune responses and alleviates dextran sodium
      sulfate-induced colitis in mice.
AB  - Diet has a significant effect on immune and inflammatory responses. To date, no
      studies have described how consumption of a diet containing a relatively high
      amount of cheese affects immune responses and the inflammatory status of the
      body. We examined these responses in normal mice and mice with dextran sodium
      sulfate (DSS)-induced colitis associated with increased inflammatory responses,
      using a diet containing approximately 44% of a whole cheese powder and a diet
      containing casein, lard, and corn oil as the control. In normal mice, consumption
      of the cheese-containing diet induced regulatory T cells (T(reg)), which regulate
      immune and inflammatory responses, and suppressed the production of IL-17, IL-4,
      and IL-10 in Peyer's patch cells from the intestine. The T(reg) population and
      cytokine production were not altered in spleen cells. In mice with DSS-induced
      colitis, consumption of the cheese-containing diet alleviated the symptoms of
      colitis, as evidenced by prevention of body weight loss and colon length
      shortening, and inhibition of an increase in the disease activity index, which
      includes diarrhea and fecal bleeding. This relief of clinical symptoms was also
      associated with decreased production of proinflammatory cytokines (IL-17 and IL
      6) and increased production of the antiinflammatory cytokine transforming growth
      factor-beta1 in Peyer's patch cells. The T(reg) population was reduced by
      consumption of the cheese-containing diet in Peyer's patch cells and spleen
      cells, which might reflect the alleviated symptoms of colitis. Consumption of the
      cheese-containing diet compared with the control diet enhanced antiinflammatory
      and immune regulatory responses in normal mice and in a DSS-colitis mouse model.

PMID- 22612917
TI  - Effect of feeding fresh forage and marine algae on the fatty acid composition and
      oxidation of milk and butter.
AB  - This study evaluated the effects of feeding fresh forage either as pasture plus a
      concentrate (PAS) or as a silage-based total mixed ration (TMR), combined with
      either a ruminally inert lipid supplement high in saturated fatty acids (-) or a
      ruminally protected microalgae containing 22 g of docosahexaenoic acid (DHA)/100
      g of fatty acids (+) on the fatty acid (FA) composition and oxidation of milk and
      butter. For the 8 mid-lactation Holstein cows in this study, milk yield was not
      significantly affected by treatment, averaging 32.3 +/- 1.28 kg/d. Milk fat
      content was higher for PAS-, averaging 5.05 compared with 4.10 +/- 0.17% for the
      mean of other treatments, and was significantly depressed with microalgae
      supplementation (3.97 vs. 4.69 +/- 0.17%). The saturated fatty acid level in the
      milk of cows fed TMR- was significantly higher than that of the other treatments
      (66.9 vs. 61.2 g/100 g of FA). The level of monounsaturated FA was lowered by
      feeding TMR- (27.4 vs. 32.0 g/100 g of FA), whereas levels of polyunsaturated FA
      were elevated by feeding PAS+ compared with the mean of the other treatments
      (6.54 vs. 5.07 g/100 g of FA). Feeding the rumen-protected microalgae increased
      the DHA content of milk more than 4-fold (0.06 to 0.26 g/100g of FA) with the PAS
      treatment. The conjugated linoleic acid content of milk was highest for PAS+
      compared with the other treatments (4.18 vs. 3.41 g/100g of FA). In general, the
      fatty acid composition of butter followed that of milk. Overall, feeding the TMR
      supplemented with the rumen-protected microalgae increased the levels of volatile
      products of oxidation in milk and butter. No effect of forage type or microalgae
      supplementation was observed on the oxidative stability or antioxidant capacity
      of milk, although the oxidative stability of butter exposed to UV was reduced
      with microalgae supplementation, particularly with TMR, as assessed by using the
      ferric reducing ability of plasma assay.

PMID- 22612919
TI  - Proteolytic activation of proteose peptone component 3 by release of a C-terminal
      peptide with antibacterial properties.
AB  - The milk protein proteose peptone component 3 (PP3, also known as lactophorin) is
      a small phosphoglycoprotein, which is exclusively expressed in the lactating
      mammary gland. A 23-residue synthetic peptide (lactophoricin, Lpcin S),
      corresponding to the C-terminal amphipathic alpha-helix of PP3, has previously
      been shown to permeabilize membranes and display antibacterial activity.
      Lactophorin readily undergoes proteolytic cleavage in milk and during dairy
      processing, and it has been suggested that PP3-derived peptides are part of
      milk's endogenous defense system against bacteria. Here, we report that a 26
      residue C-terminal peptide (Lpcin P) can be generated by trypsin proteolysis of
      PP3 and that structural and functional studies of Lpcin P indicate that the
      peptide has antibacterial properties. The Lpcin P showed alpha-helical structure
      in both anionic and organic solvents, and the amount of alpha-helical structure
      was increased in the presence of lipid vesicles. Oriented circular dichroism
      showed that Lpcin P oriented parallel to the membrane surface. However, the
      peptide permeabilized calcein-containing vesicles efficiently. Lpcin P displayed
      antibacterial activity against Streptococcus thermophilus, but not against
      Staphylococcus aureus and Escherichia coli. The PP3 full-length protein did not
      display the same properties, which could indicate that PP3 functions as a
      precursor protein that upon proteolysis, releases a bioactive antibacterial
      peptide.

PMID- 22612920
TI  - Manufacture of reduced-sodium Cheddar-style cheese with mineral salt replacers.
AB  - The use of mineral salt replacers to reduce the sodium content in cheese has been
      investigated as a method to maintain both the salty flavor and the preservative
      effects of salt. The majority of studies of sodium reduction have used mineral
      salt replacers at levels too low to produce equal water activity (a(w)) in the
      finished cheese compared with the full-sodium control. Higher a(w) can result in
      differences in cheese quality due to differences in the effective salt-to
      moisture ratio. This creates differences in biochemical and microbial reactions
      during aging. We hypothesized that by targeting replacer concentrations to
      produce the same a(w) as full sodium cheese, changes in cheese quality would be
      minimized. Stirred-curd Cheddar-style cheese was manufactured and curd was salted
      with NaCl or naturally reduced sodium sea salt. Reduced-sodium cheeses were
      created by blends of NaCl or sea salt with KCl, modified KCl, MgCl2, or CaCl2
      before pressing. Sodium levels in reduced-sodium cheeses ranged from 298 to 388
      mg of sodium/100g, whereas the control full-sodium cheese had 665 mg/100g. At 1
      wk of age, a(w) of reduced-sodium cheeses were not significantly different from
      control, which had an a(w) of 0.96. The pH values of all reduced-sodium cheeses,
      excluding the treatment that combined sea salt and MgCl2, were lower than those
      of full-sodium cheese, indicating that the starter culture was possibly less
      inhibited at the salting step by the replacers than by NaCl. Instrumental
      hardness values of the treatments with sea salt were higher than in cheeses
      containing NaCl, with the exception of the NaCl/CaCl2 treatment, which was the
      hardest. Treatments with MgCl2 and modified KCl were generally less hard than
      other treatments. In-hand and first-bite firmness values correlated with the
      instrumental texture profile analysis results. Both CaCl2 and MgCl2 produced
      considerable off-flavors in the cheese (bitter, metallic, unclean, and soapy), as
      measured by descriptive sensory analysis with a trained panel. Bitterness ratings
      for cheese with KCl and modified KCl were not significantly different from the
      full-sodium control. Potassium chloride can be used successfully to achieve large
      reductions in sodium when replacing a portion of the NaCl in Cheddar cheese.

PMID- 22612921
TI  - Effect of zinc fortification on Cheddar cheese quality.
AB  - Zinc-fortified Cheddar cheese containing 228 mg of zinc/kg of cheese was
      manufactured from milk that had 16 mg/kg food-grade zinc sulfate added. Cheeses
      were aged for 2 mo. Culture activity during cheese making and ripening, and
      compositional, chemical, texture, and sensory characteristics were compared with
      control cheese with no zinc sulfate added to the cheese milk. Compositional
      analysis included fat, protein, ash, moisture, zinc, and calcium determinations.
      The thiobarbituric acid (TBA) assay was conducted to determine lipid oxidation
      during aging. Texture was analyzed by a texture analyzer. An untrained consumer
      panel of 60 subjects evaluated the cheeses for hardness, off-flavors, appearance,
      and overall preference using a 9-point hedonic scale. Almost 100% of the zinc
      added to cheese milk was recovered in the zinc-fortified cheese. Zinc-fortified
      Cheddar cheese had 5 times more zinc compared with control cheese. Zinc-fortified
      cheese had higher protein and slightly higher fat and ash contents, whereas
      moisture was similar for both cheeses. Zinc fortification did not affect culture
      activity during cheese making or during the 2-mo aging period. The TBA value of
      control cheese was higher than that of zinc-fortified cheese at the end of
      ripening. Although zinc-fortified cheese was harder as determined by the texture
      analyzer, the untrained consumer panel did not detect differences in the sensory
      attributes and overall quality of the cheeses. Fortification of 16 mg/kg zinc
      sulfate in cheese milk is a suitable approach to fortifying Cheddar cheese
      without changing the quality of Cheddar cheese.

PMID- 22612922
TI  - Effect of bleaching whey on sensory and functional properties of 80% whey protein
      concentrate.
AB  - Whey is a highly functional food that has found widespread use in a variety of
      food and beverage applications. A large amount of the whey proteins produced in
      the United States is derived from annatto-colored Cheddar cheese. Color from
      annatto is undesirable in whey and must be bleached. The objective of this study
      was to compare 2 commercially approved bleaching agents, benzoyl peroxide (BP)
      and hydrogen peroxide (HP), and their effects on the flavor and functionality of
      80% whey protein concentrate (WPC80). Colored and uncolored liquid wheys were
      bleached with BP or HP, and then ultrafiltered, diafiltered, and spray-dried;
      WPC80 from unbleached colored and uncolored Cheddar whey were manufactured as
      controls. All treatments were manufactured in triplicate. The WPC80 were then
      assessed by sensory, instrumental, functionality, color, and proximate analysis
      techniques. The HP-bleached WPC80 were higher in lipid oxidation compounds
      (specifically hexanal, heptanal, octanal, nonanal, decanal, dimethyl disulfide,
      and 1-octen-3-one) and had higher fatty and cardboard flavors compared with the
      other unbleached and BP-bleached WPC80. The WPC80 bleached with BP had lower
      norbixin concentrations compared with WPC80 bleached with HP. The WPC powders
      differed in Hunter color values (L, a, b), with bleached powders being more
      white, less red, and less yellow than unbleached powders. Bleaching with BP under
      the conditions used in this study resulted in larger reductions in yellowness of
      the powders made from whey with annatto color than did bleaching with HP.
      Functionality testing demonstrated that whey bleached with HP treatments had more
      soluble protein after 10 min of heating at 90 degrees C at pH 4.6 and pH 7 than
      the no-bleach and BP treatments, regardless of additional color. Overall, HP
      bleaching caused more lipid oxidation products and subsequent off-flavors
      compared with BP bleaching. However, heat stability of WPC80 was enhanced by HP
      bleaching compared with control or BP-bleached WPC80.

PMID- 22612923
TI  - A derivative of Lactococcus lactis strain H61 with less interleukin-12 induction
      has a different cell wall.
AB  - Lactococcus lactis H61 can increase the cellular immune responses of aged (14-mo
      old) senescence-accelerated mice. The aim of this study was to investigate the
      factors contributing to IL-12 induction by strain H61 by analyzing strains
      derived from it. Strain H61 derivative no. 13 was obtained by growing the parent
      strain at 37 degrees C. This derivative induced significantly lower production of
      IL-12 from J774.1 macrophage cells than did the parent strain H61. The 2 strains
      differed in the resistance of their whole cells or cell walls to lysozyme, a cell
      wall-degrading enzyme. Sodium hydroxide treatment to de-O-acetylate muramic acid
      in the cell walls of the 2 strains reduced the lysozyme resistance, compared with
      untreated cell walls: at 3h after adding lysozyme, the lysozyme resistance of
      untreated and NaOH treated cell wall from strain H61 was 55.4% and 11.7%,
      respectively. The values of untreated and NaOH-treated cell walls from strain
      no.13 were 73.7 and 42.8%, respectively. The reduction was higher in strain H61,
      indicating that the cell walls of strain H61 were highly O-acetylated.
      Trichloroacetic acid treatment to remove wall-associated polymers such as
      teichoic acids made the lysozyme resistance of the cell walls of both strains
      similar. The sugar content of cell walls prepared from strain H61 was
      significantly higher than that of strain no. 13 cell wall. A derivative with less
      activity for inducing IL-12 by macrophage cells had less O-acetylation and had
      lower sugar content in the cell wall than did strain H61. Modifying the cell wall
      of strain H61 may be a useful way to regulate its ability to induce IL-12. Strain
      H61 has been used as a starter bacterium in the dairy industry. This study could
      lead to enhancing the value of dairy products made by strain H61 by
      characterizing the key factor(s) responsible for its stimulation of immunity.

PMID- 22612924
TI  - Rapid determination of sodium in milk and milk products by capillary zone
      electrophoresis.
AB  - A capillary zone electrophoresis method for the determination of Na in milk and
      milk products was developed and compared with an International Organization for
      Standardization/International Dairy Federation standard method that is based on
      flame atomic absorption spectrometry. The adoption of a background electrolyte
      consisting of 10 mM imidazole adjusted to pH 3.75 by the addition of oxalic acid
      allowed baseline separation of Na from other milk cations and from Li ion, which
      was adopted as an internal standard. Method validation was performed and the
      results for linearity, precision, limit of detection, limit of quantification,
      and recovery are presented. The procedure was tested on commercial milk samples
      differing in fat content (whole, semiskimmed, and skimmed) and processing
      conditions (pasteurization, UHT sterilization, and microfiltration). The
      reliability of the method was confirmed for different varieties of cheese and
      other milk products. The method enables the routine measurement of Na content by
      a rapid and accurate capillary zone electrophoresis procedure.

PMID- 22612925
TI  - The use of lactoperoxidase for the bleaching of fluid whey.
AB  - Lactoperoxidase (LP) is the second most abundant enzyme in bovine milk and has
      been used in conjunction with hydrogen peroxide (H2O2) and thiocyanate (SCN-) to
      work as an antimicrobial in raw milk where pasteurization is not feasible.
      Thiocyanate is naturally present and the lactoperoxidase system purportedly can
      be used to bleach dairy products, such as whey, with the addition of very little
      H2O2 to the system. This study had 3 objectives: 1) to quantify the amount of
      H2O2 necessary for bleaching of fluid whey using the LP system, 2) to monitor LP
      activity from raw milk through manufacture of liquid whey, and 3) to compare the
      flavor of whey protein concentrate 80% (WPC80) bleached by the LP system to that
      bleached by traditional H2O2 bleaching. Cheddar cheese whey with annatto (15 mL
      of annatto/454 kg of milk, annatto with 3% wt/vol norbixin content) was
      manufactured using a standard Cheddar cheesemaking procedure. Various levels of
      H2O2 (5-100 mg/kg) were added to fluid whey to determine the optimum
      concentration of H2O2 for LP activity, which was measured using an established
      colorimetric method. In subsequent experiments, fat-separated whey was bleached
      for 1h with 250 mg of H2O2/kg (traditional) or 20 mg of H2O2/kg (LP system). The
      WPC80 was manufactured from whey bleached with 250 mg of H2O2/kg or 20mg of
      H2O2/kg. All samples were subjected to color analysis (Hunter color values and
      norbixin extraction) and proximate analysis (fat, protein, and moisture). Sensory
      and instrumental volatile analyses were conducted on WPC80. Optimal LP bleaching
      in fluid whey occurred with the addition of 20mg of H2O2/kg. Bleaching of fluid
      whey at either 35 or 50 degrees C for 1 h with LP resulted in > 99% norbixin
      destruction compared with 32 or 47% destruction from bleaching with 250 mg of
      H2O2/kg, at 35 or 50 degrees C for 1 h, respectively. Higher aroma intensity and
      increased lipid oxidation compounds were documented in WPC80 from bleached whey
      compared with WPC80 from unbleached whey. Monitoring of LP activity throughout
      cheese and whey manufacture showed that LP activity sharply decreased after 30
      min of bleaching (17.01 +/- 1.4 to < 1 U/mL), suggesting that sufficient
      bleaching takes place in a very short amount of time. Lactoperoxidase averaged
      13.01 +/- 0.7 U/mL in unpasteurized, fat-separated liquid whey and 138.6 +/- 11.9
      U/mL in concentrated retentate (11% solids). Lactoperoxidase may be a viable
      alternative for chemical whey bleaching.

PMID- 22612926
TI  - Milk protein genetic variants and isoforms identified in bovine milk representing
      extremes in coagulation properties.
AB  - A gel-based proteomic approach consisting of 2-dimensional gel electrophoresis
      coupled with mass spectrometry was applied for detailed protein characterization
      of a subset of individual milk samples with extreme rennet coagulation
      properties. A milk subset with either good or poor coagulation abilities was
      selected from 892 Danish Holstein-Friesian and Jersey cows. Screening of genetic
      variants of the major milk proteins resulted in the identification of common
      genetic variants of beta-casein (CN; A(1), A(2), B), kappa-CN (A, B), and beta
      lactoglobulin (LG; A, B), as well as a low frequency variant, kappa-CN variant E,
      and variants not previously reported in Danish breeds (i.e., beta-CN variant I
      and beta-LG variant C). Clear differences in the frequencies of the identified
      genetic variants were evident between breeds and, to some extent, between
      coagulation groups within breeds, indicating that an underlying genetic variation
      of the major milk proteins affects the overall milk coagulation ability. In milk
      with good coagulation ability, a high prevalence of the B variants of all 3
      analyzed proteins were identified, whereas poorly coagulating milk was associated
      with the beta-CN variant A(2), kappa-CN variant A or E, and beta-LG variant A or
      C. The beta-CN variant I was identified in milk with both good and poor
      coagulation ability, a variant that has not usually been discriminated from beta
      CN variant A(2) in other studied cow populations. Additionally, a detailed
      characterization of kappa-CN isoforms was conducted. Six kappa-CN isoforms
      varying in phosphorylation and glycosylation levels from each of the genetic
      variants of kappa-CN were separated and identified, along with an unmodified
      kappa-CN form at low abundance. Relative quantification showed that around 95% of
      total kappa-CN was phosphorylated with 1 or 2 phosphates attached, whereas
      approximately 35% of the identified kappa-CN was glycosylated with 1 to 3
      tetrasaccharides. Comparing isoforms from individual samples, we found a very
      consistent kappa-CN isoform pattern, with only minor differences in relation to
      breed, kappa-CN genetic variant, and milk coagulation ability.

PMID- 22612927
TI  - Short communication: effect of oxygen on symbiosis between Lactobacillus
      bulgaricus and Streptococcus thermophilus.
AB  - Lactobacillus delbrueckii ssp. bulgaricus (L. bulgaricus) and Streptococcus
      thermophilus are traditionally used for the manufacture of yogurt. It is said
      that a symbiotic relationship exists between Strep. thermophilus and L.
      bulgaricus and this decreases fermentation time. It is well known that L.
      bulgaricus is stimulated by the formate produced by Strep. thermophilus, and
      Strep. thermophilus is stimulated by free amino acids and peptides liberated from
      milk proteins by L. bulgaricus in symbiotic fermentation. We found that acid
      production by starter culture LB81 composed of L. bulgaricus 2038 and Strep.
      thermophilus 1131 was greatly accelerated by decreasing dissolved oxygen (DO) to
      almost 0 mg/kg in the yogurt mix (reduced dissolved oxygen fermentation) and that
      DO interferes with the symbiotic relationship between L. bulgaricus 2038 and
      Strep. thermophilus 1131. We attributed the acceleration of acid production of
      LB81 by reduced dissolved oxygen fermentation mainly to the acceleration of
      formate production and the suppression of acid production of LB81 by DO mainly to
      the suppression of formate production.

PMID- 22612928
TI  - Short communication: jenny milk production and qualitative characteristics.
AB  - The aim of this research was to study the influence of lactation stage and
      foaling season on some qualitative aspects of milk in South Italian jenny
      rearing. Milk samples were collected monthly from 23 jennies, that foaled in 2
      different periods: spring and summer. On milk, the following parameters were
      measured: pH and titratable acidity; protein, fat, lactose, dry matter, and ash
      contents; and somatic cell count. Analysis of variance showed the effect of
      foaling season and of lactation stage. Milk production was highest in summer at
      30 d and 60 d (1.58 and 1.78 L, respectively), and in spring at 120 d (1.25 L).
      The total protein content was highest in summer lactation at 30 d and 90 d (14.8
      and 13.9 g/L). Lactose, dry matter, and ash contents (g/L) were highest in summer
      lactation at 30 d (54.0, 78.1, and 5.0 respectively). Jenny milk was shown to be
      poor in protein and fat and rich in lactose. Producing jenny milk could be an
      interesting, profitable, and alternative activity for farmers, mainly in southern
      marginal areas.

PMID- 22612929
TI  - Short communication: appropriate and alternative methods to determine viable
      bacterial counts in cow milk samples.
AB  - Farm milk consumption is reported to be inversely related to the development of
      asthma and atopy in children and it has been hypothesized that microorganisms in
      milk might contribute to this protective effect. The GABRIEL study was designed
      to investigate this hypothesis in a large population of European children,
      calling for a rapid alternative to classical culture techniques to determine
      bacteriological properties of milk samples. One objective was to evaluate 2
      different rapid methods to determine bacteriological properties in a large number
      of cow milk samples collected under field conditions. BactoScan (Foss Analytical,
      Hillerod, Denmark), an automated standard flow cytometric method utilized for
      routine testing of milk quality, and TEMPO (bioMerieux, Marcy l'Etoile, France),
      an automated most-probable-number method, were used to assess the total viable
      bacterial count in farm and commercial milk samples. Both methods were compared
      with standard plate count method and each other. Measurements based on the TEMPO
      method were in good agreement with the standard plate count method and showed
      reliable results, whereas BactoScan results did not correlate with standard plate
      count measurements and yielded higher bacteria counts in heat-treated milk
      samples compared with raw milk samples. Most likely, these discrepant results
      were due to inferences with staining reactions and detection of bacteria in heat
      treated milk samples. We conclude that, in contrast to the routinely used
      BactoScan method, the TEMPO method is an inexpensive and rapid alternative to
      standard culture methods suitable to assess total bacterial counts in processed
      and raw milk samples.

PMID- 22612930
TI  - A model of ruminal volatile fatty acid absorption kinetics and rumen epithelial
      blood flow in lactating Holstein cows.
AB  - Ruminal absorption of volatile fatty acids (VFA) is quantitatively the most
      important nutrient flux in cattle. Historically, VFA absorption models have been
      derived primarily from ruminal variables such as chemical composition of the
      fluid, volume, and pH. Recently, a mechanistic model incorporated the control of
      VFA absorption from epithelial surface area of the reticulorumen. In the present
      study, we hypothesized that ruminal absorption of VFA was controlled through
      epithelial permeability to VFA and rumen epithelial capillary blood flow. The
      objective of the study was to construct a model of VFA exchange across the rumen
      wall that incorporates epithelial blood flow as a driving force for ruminal VFA
      removal. The bidirectional fluxes between the ruminal and epithelial pool of VFA
      were assumed mass action driven, given that passive diffusion of nonionized VFA
      is the dominant transmembrane VFA flux. Parameter estimates were derived by
      fitting the model to observed data. The model provided reliable unbiased
      estimates of ruminal VFA absorption and rumen epithelial blood flow. Blood flow
      was modeled using an equation that considered the effect of butyrate and dietary
      crude protein intake per kilogram of body weight. The rate constants related to
      the flux from ruminal fluid to epithelium were in the order isobutyrate < acetate
      < propionate < butyrate (0.32 +/- 0.02, 0.72 +/- 0.2, 0.91 +/- 0.06, and 0.97 +/-
      0.02 /h, respectively). The rate constants for fluxes of isobutyrate, acetate,
      propionate, and butyrate from the rumen epithelium to the ruminal fluid, relative
      to the pool size of the epithelium, were 4.78, 10.6, 13.4, and 14.3 /h,
      respectively. Ruminal concentrations of acetate, propionate, butyrate, and
      isobutyrate were predicted with root mean square prediction errors as percentage
      of the observed means (RMSPE) of 5.86, 5.75, 11.3, and 4.12, respectively. The
      epithelial blood flow was predicted with 26.3% RMSPE. Sensitivity analyses
      indicated that when ruminal butyrate concentration increased from 4.0 to 37.4
      mmol/L, blood flow of the epithelium increased 47% and the ruminal disappearance
      rate of propionate increased 11%. The concentration gradient of propionate
      between ruminal fluid and epithelium was no more than 3:1 and increased with
      increasing blood flow. In conclusion, a dynamic model based on rumen epithelial
      blood flow and bidirectional fluxes of VFA between ruminal fluid and epithelium
      gave unbiased predictions with low residual error of ruminal VFA absorption under
      washed rumen conditions. The model indicates that the effect of varying
      epithelial blood flow on the control of ruminal VFA absorption is related to the
      concentration gradient of individual VFA between ruminal fluid and epithelial
      blood. Epithelial blood flow may be an important determinant of ruminal
      absorption of VFA, a result that has not been evaluated on independent data.

PMID- 22612932
TI  - Evaluating an intervention to reduce lameness in dairy cattle.
AB  - Lameness in dairy cattle remains a significant welfare concern for the UK dairy
      industry. Farms were recruited into a 3-yr study evaluating novel intervention
      approaches designed to encourage farmers to implement husbandry changes targeted
      toward reducing lameness. All farms completing the study were visited at least
      annually and received either monitoring only (MO, n=72) or monitoring and
      additional support (MS, n = 117) from the research team. The additional support
      included traditional technical advice on farm-specific solutions, facilitation
      techniques to encourage farmer participation, and application of social marketing
      principles to promote implementation of change. Lameness prevalence was lower in
      the MO (27.0 +/- 1.94 SEM) and MS (21.4 +/- 1.28) farms at the final visit
      compared with the same MO (38.9 +/- 2.06) and MS (33.3 +/- 1.76) farms on the
      initial visit. After accounting for initial lameness, intervention group status,
      and year of visit within a multilevel model, we observed an interaction between
      year and provision of support, with the reduction in lameness over time being
      greater in the MS group compared with the MO group. Farms in the MS group made a
      greater number of changes to their husbandry practices over the duration of the
      project (8.2 +/- 0.39) compared with those farms in the MO group (6.5 +/- 0.54).
      Because the lameness prevalence was lower in the MS group than the MO group at
      the start of the study, the contribution of the additional support was difficult
      to define. Lameness can be reduced on UK dairy farms although further work is
      needed to identify the optimum approaches.

PMID- 22612931
TI  - Selection of suitable reference genes for quantitative gene expression studies in
      milk somatic cells of lactating cows (Bos indicus).
AB  - We assessed the suitability of 9 internal control genes (ICG) in milk somatic
      cells of lactating cows to find suitable reference genes for use in quantitative
      PCR (qPCR). Eighteen multiparous lactating Sahiwal cows were used, 6 in each of 3
      lactation stages: early (25 +/- 5 d in milk), mid (160 +/- 15 d in milk), and
      late (275 +/- 25 d in milk) lactation. Nine candidate reference genes
      [glyceraldehyde 3-phosphate dehydrogenase (GAPDH), protein phosphatase 1
      regulatory subunit 11 (PPP1R11), beta-actin (ACTB), beta-2 microglobulin (B2M),
      40S ribosomal protein S15a (RPS15A), ubiquitously expressed transcript (UXT),
      mitochondrial GTPase 1 (MTG1), 18S rRNA (RN18S1), and ubiquitin (UBC)] were
      evaluated. Three genes, beta-casein (CSN2), lactoferrin (LTF), and cathelicidin
      (CAMP) were chosen as target genes. Very high amplification was observed in 7 ICG
      and very low level amplification was observed in 2 ICG (UXT and MTG1). Thus, UXT
      and MTG1 were excluded from further analysis. The qPCR data were analyzed by 2
      software packages, geNorm and NormFinder, to determine suitable reference genes,
      based on their stability and expression. Overall, PPP1R11, ACTB, UBC, and GAPDH
      were stably expressed among all candidate reference genes. Therefore, these genes
      could be used as ICG for normalization of qPCR data in milk somatic cells through
      lactation.

PMID- 22612933
TI  - Effectiveness of different footbathing frequencies using copper sulfate in the
      control of digital dermatitis in dairy cows.
AB  - Two experiments were conducted to test the effectiveness of different footbathing
      frequencies using CuSO4 in the control of digital dermatitis (DD) in groups of
      dairy cows with low and high DD prevalence in an endemically infected herd.
      During the study, groups of cows walked through allocated footbath solutions
      after milking on 4 consecutive milkings each week, 2 wk, or monthly, depending on
      treatment. The footbath solutions were changed either after 200 cows had passed
      through the footbath or within 24 h. All cows were scored weekly during milking
      for DD lesion stage on the hind feet using a 5-point nominal scale. A transition
      grade was assigned based on whether the DD lesions improved (1) or deteriorated
      or did not improve (0) from week to week, and was averaged for all cows in the
      group. Furthermore, from the longitudinal study data, all transitions between
      different DD lesion stages between the different time points were used in a
      discrete, first-order Markov chain (state transition matrix) model. In experiment
      1, 70 Holstein-Friesian cows with DD lesions present on at least one of their
      hind feet were allocated to 1 of 2 footbath treatments for 14 wk: (1) 5% CuSO4
      each week or (2) 5% CuSO4 every 2 wk. At the end of the study, no active DD
      lesions were observed in cows in either treatment group, but significantly more
      cows had no DD lesions (0.48 +/- 0.097 vs. 0.24 +/- 0.094) and fewer cows had
      lesions in the healing stage (0.52 +/- 0.104 vs. 0.77 +/- 0.090) for the weekly
      compared with the 2-wk footbathing regimen. The number of active DD lesions that
      the transition matrix model predicted over time was 3 and 8% for weekly and every
      2 wk footbathing treatments, respectively. In experiment 2, 64 cows with no DD
      lesions on either of their hind feet were allocated to 1 of 2 footbath treatment
      regimens for 14 wk: (1) 5% CuSO4 every 2 wk or (2) 5% CuSO4 each month. At the
      end of the trial, significantly more cows had no DD (0.80 +/- 0.088 vs. 0.65 +/-
      0.102) and fewer cows had DD lesions in the healing stage (0.20 +/- 0.088 vs.
      0.35 +/- 0.102) in the every 2 wk regimen than in the monthly footbathing
      regimen. The number of active DD lesions that the transition matrix model
      predicted over time was low for both footbathing interventions (1 and 4%,
      respectively). Increasing the interval between footbaths does not appear the most
      appropriate mechanism for reducing CuSO4 usage.

PMID- 22612934
TI  - Myoepithelial cell differentiation markers in prepubertal bovine mammary gland:
      effect of ovariectomy.
AB  - We reported previously that ovariectomy alters prepubertal development of mammary
      myoepithelial cells (MC) by mechanisms that are not well understood. Therefore,
      in the present study, we analyzed expression of 2 myoepithelial differentiation
      markers, alpha-smooth muscle actin (SMA) and the common acute lymphoblastic
      leukemia antigen (CD10), in mammary parenchymal tissue from intact (INT) and
      ovariectomized (OVX) heifers. On d 40, Holstein heifers underwent either an
      ovariectomy (OVX; n=16) or a sham (INT; n=21) operation. At 55, 70, 85, 100, 130,
      and 160 d of age, tissues were collected, and multispectral imaging was used to
      quantify immunofluorescent staining for myoepithelial cell (MC) markers.
      Fluorescent intensity (FI) of the markers was normalized against a control
      sample. In the basal epithelial layer, CD10 FI was less and SMA FI was greater in
      OVX than INT. The ratio of SMA to CD10 FI, as a proxy indicator for MC
      differentiation, was greater in tissue from OVX compared with INT heifers after
      55 d of age. The staining for SMA was frequently more intense along the basal
      aspect of cells, whereas CD10 expression was localized on the apical surface of
      the MC. In mammary tissue from both INT and OVX heifers, we observed basal cells
      that were negative for both CD10 and SMA, some of which appeared to span the
      distance from basement membrane to the ductal lumen. Interestingly, we also
      observed CD10+ cells adjacent to the ductal lumen, a situation that was more
      prevalent in OVX than in INT heifers. Also, ovariectomy affects MC expression of
      both SMA and CD10, as well as the pattern of MC development. Myoepithelial cells
      are known to limit parenchymal growth in other species. Involvement of MC as
      regulators of prepubertal bovine mammary development is worthy of further
      investigation.

PMID- 22612935
TI  - The economic effects of whole-herd versus selective anthelmintic treatment
      strategies in dairy cows.
AB  - Current control practices against gastrointestinal nematodes in dairy cows rely
      strongly on anthelmintic use. To reduce the development of anthelmintic
      resistance or disposition of drug residues in the environment, novel control
      approaches are currently proposed that target anthelmintic treatment to
      individual animals instead of the whole herd. However, such selective treatment
      strategies come with additional costs for labor and diagnostics and, so far, no
      studies have addressed whether they could be economically sustainable. The
      objectives of this study were to (1) investigate the economic effects at farm
      level of whole-herd versus more selective anthelmintic treatment strategies in
      adult dairy cows, and (2) determine how these economic effects depend on level of
      infection and herd size. A Monte Carlo simulation, fed by current epidemiological
      and economical knowledge, was used to estimate the expected economic effects and
      possible variation of different control strategies under Belgian conditions. Four
      treatment strategies were compared with a baseline situation in which no
      treatments were applied: whole herd at calving (S1), selective at calving with
      (S2) or without (S3) treatment of the first-calf cows, and whole-herd when
      animals are moved from grazing to the barn in the fall (housing treatment, S4).
      The benefit per lactation for an average dairy herd varied between -$2 and $131
      (average $64) for S1, between -$2 and $127 (average $62) for S2, between -$17 and
      $104 (average $43) for S3, and between -$41 and $72 (average $15) for S4. The
      farmer's risk associated with any treatment strategy, as indicated by the width
      of the 95% credible intervals of economic benefit of anthelmintic treatment,
      decreased with increasing level of exposure, as assessed by bulk tank milk ELISA.
      The order of the different strategies when sorted by expected benefit was robust
      to changes in economic input parameters. We conclude that, on average, strategies
      applying anthelmintic treatment at calving outperform a strategy applying
      treatment at housing. Within the strategies that applied treatment at calving,
      more selective treatment strategies can be economically sustainable. However,
      given the large variation in possible benefits within each treatment strategy,
      decision support systems are needed to account for the multitude of cow,
      epidemiological, and economic factors that determine the economics of nematode
      control and select the optimal treatment strategy for a specific farm.

PMID- 22612936
TI  - On-farm evaluation of the effect of metabolic diseases on the shape of the
      lactation curve in dairy cows through the MilkBot lactation model.
AB  - The effects of metabolic diseases (MD) occurring during the transition period on
      milk production of dairy cows have been evaluated in many different ways, often
      with conflicting conclusions. The present study used a fitted lactation model to
      analyze specific aspects of lactation curve shape and magnitude in cows that
      avoided culling or death in the first 120 d in milk (DIM). Production and health
      records of 1,946 lactations in a 1-yr follow-up study design were collected from
      a transition management facility in Germany to evaluate both short- and long-term
      effects of MD on milk production. Milk production data were fitted with the
      nonlinear MilkBot lactation model, and health records were used to classify cows
      as healthy (H), affected by one MD (MD), or by multiple MD (MD+). The final data
      set contained 1,071 H, 348 MD, and 136 MD+ cows, with distinct incidences of 3.7%
      twinning, 4.8% milk fever, 3.6% retained placenta, 15.4% metritis, 8.3% ketosis,
      2.0% displaced abomasum, and 3.7% mastitis in the first 30 DIM. The model
      containing all healthy and diseased cows showed that lactations classified as H
      had milk production that increased faster (lower ramp) and also declined faster
      (lower persistence) compared with cows that encountered one or more metabolic
      problems. The level of production (scale) was only lowered in MD+ cows compared
      with H and MD cows. Although the shape of the lactation curve changed when cows
      encounter uncomplicated (single) MD or complicated MD (more than one MD), the
      slower increase to a lower peak seemed to be compensated for by greater
      persistency, resulting in the overall 305-d milk production only being lowered in
      MD+ cows. In the individual disease models, specific changes in the shape of the
      lactation curve were found for all MD except twinning. Milk fever, retained
      placenta, ketosis, and mastitis mainly affected the lactation curve when
      accompanied by another MD, whereas metritis and displaced abomasum affected the
      lactation curve equally with or without another MD. Overall, 305-d milk
      production was decreased in complicated metritis (10,603 +/- 50 kg vs. 10,114 +/-
      172 kg). Although care should be taken in generalizing conclusions from a highly
      specialized transition management facility, the current study demonstrated that
      lactation curve analysis may contribute substantially to the evaluation of both
      short- and long-term effects of metabolic diseases on milk production by
      detecting changes in the distribution of production that are not apparent when
      only totals are analyzed.

PMID- 22612937
TI  - Quantification and at-risk period of decreased fertility associated with exposure
      to bluetongue virus serotype 8 in naive dairy herds.
AB  - The detrimental effect of bluetongue virus serotype 8 (BTV-8) on fertility was
      quantified in seroconverting cows. Although the effect on individual cows
      provides information regarding the potential biological burden of infection,
      losses at a herd level are also dependent on the proportion of infected cows
      within the herd. The objectives of this study were to quantify the average effect
      of BTV-8 exposure in field conditions on the fertility of dairy cows in
      previously naive herds, and to determine the at-risk period of decreased
      fertility related to the date of detection of the disease in the herd. The effect
      of BTV-8 exposure on fertility was assessed using the 90-d-return-to-service
      rates after the first artificial insemination (AI) calculated for cows in exposed
      herds (during the 2007 epizootic in France) and compared with that for cows in
      unexposed herds. Only herds with a confirmed detection that were reported after
      clinical suspicion were included. To determine the at-risk period of decreased
      fertility, variations of fertility in exposed herds were quantified according to
      the time interval between the date of AI for individual cows and the date that
      disease was detected in the herd. Survival analyses were used to assess the risk
      of decreased fertility associated with BTV-8 exposure, adjusting for the main
      factors known to influence fertility. The episode at risk for decreased fertility
      depended on the month of disease detection in the herd. For herds detected early
      in the epizootic, fertility was decreased for cows inseminated from 1 mo before
      to 1 mo after the date of disease detection in the herd. Depending on time
      interval between the date of AI of cows and the date of detection in the herd,
      the increase of return-to-service rate associated with BTV-8 exposure varied from
      8 to 21 percentage points of 90-d return to service. The episode of decreased
      fertility is likely due to a combination of the effect of the infection at
      different stages of conception and early pregnancy and the delayed exposure of
      cows due to the spreading of the virus within herds. For herds detected during
      the second half of the epizootic, fertility was decreased for cows inseminated
      more than 2 mo before detection, which suggests a delay in the detection of
      clinical signs following virus introduction in the herd. No correlation was
      observed between the effect of BTV-8 exposure on fertility and the incidence of
      BTV-8 in the local geographical area. Given the duration of the period that cows
      were at risk for decreased fertility and the magnitude of the effect, the average
      BTV-8 exposure in naive herds led to major losses.

PMID- 22612938
TI  - Radiant heat loss, an unexploited path for heat stress reduction in shaded
      cattle.
AB  - Reducing thermal radiation on shaded animals reduces heat stress independently of
      other means of stress relief. Radiant heat exchange was estimated as a function
      of climate, shade structure, and animal density. Body surface portion exposed to
      radiant sources in shaded environments was determined by geometrical relations to
      determine angles of view of radiation sources (roof underside, sky, sun-exposed
      ground, shaded ground) on the animal's surface. The relative representation of
      environment radiation sources on the body surface was determined. Animal thermal
      radiation balance was derived from radiant heat gained from radiation sources
      (including surrounding animals) and that lost from the animal surface. The animal
      environment was assumed to have different shade dimensions and temperatures.
      These were summed to the radiant heat balance of the cow. The data formed served
      to estimate the effect of changes in intensity of radiation sources, roof and
      shaded surface dimensions, and animal density on radiant heat balance (Rbal) of
      cattle. Roof height effect was expressed by effect of roof temperature on Rbal.
      Roof underside temperature (35 to 75 degrees C) effect on Rbal was reduced by
      roof height. If roof height were 4m, an increase in its underside temperature
      from 35 to 75 degrees C would increase mean Rbal from -63 to -2 W.m-2, whereas if
      roof height were 10 m, Rbal would only increase from -99 to -88 W.m-2. A hot
      ground temperature increase from 35 to 65 degrees C reduced mean Rbal heat loss
      from -45 to 3 W.m-2. Increasing the surface of the shaded area had only a minor
      effect on Rbal and on the effect of hot ground on Rbal. Increasing shade roof
      height reduced the effect of roof temperature on Rbal to minor levels when height
      was > 8m. Increasing the roof height from 4 to 10 m decreased Rbal from -32 to 
      94 W.m-2. Increasing indirect radiation from 100 to 500 W.m-2 was associated with
      an increase in Rbal from -135 to +23 W.m-2. Their combined effects were lower
      Rbal with increasing roof height and a reduction in rate of decrease with
      increasing level of indirect radiation. Roof height as an Rbal attenuator
      declined with increasing indirect radiation level. The latter factor might be
      reduced by lowering roof surface radiation absorption and through roof heat
      transfer, as well as by use of shade structure elements to reduce indirect
      radiation in the shaded area. Radiant heat from the cow body surface may be
      reduced by lower cow density. Radiant heat attenuation may thus further elevate
      animal productivity in warm climates, with no associated operation costs.

PMID- 22612939
TI  - Immunohistochemical characterization of phagocytic immune cell infiltration into
      different adipose tissue depots of dairy cows during early lactation.
AB  - The present study aimed to investigate whether phagocytic immune cells infiltrate
      into bovine adipose tissue (AT) and to study the effects of lactation and
      conjugated linoleic acid (CLA) supplementation on the invasion of phagocytic
      immune cells into different s.c. and visceral (v.c.) fat depots of primiparous
      dairy cows during the first 105 d in milk (DIM). German Holstein-Friesian cows
      (HF; n = 25) with a mean body condition score of 3.0 were divided into a control
      (CON) and a CLA group. From 1 DIM until sample collection, CLA cows were fed 100
      g of CLA supplement/d (about 6% of c9,t11 and t10,c12 isomers each), whereas the
      CON cows received 100 g/d of a fatty acid mixture instead of CLA. The CON cows (n
      = 5 each) were slaughtered at 1, 42, and 105 DIM, and the CLA cows (n = 5 each)
      were slaughtered at 42 and 105 DIM. Adipose tissues (n = 150) from 3s.c.
      (tailhead, withers, and sternum) and 3 v.c. (omental, mesenteric, and
      retroperitoneal) depots were sampled. In addition, s.c. tailhead biopsies were
      collected by repeated surgical biopsies (3 samplings within 7 wk; n = 36) from 12
      nonpregnant, nonlactating Simmental heifers (SM; mean body condition score = 5.0)
      fed diets of varying energy density to compare the changes in phagocytic immune
      cell infiltration with early lactating cows. Immunohistochemical analyses of
      different fat depots revealed a low incidence of phagocytic immune cell
      infiltration in early lactating cows. The portion of infiltrating macrophages
      (CD68+) in a few positive AT samples of HF cows was slightly lower in s.c. than
      v.c. fat and was positively correlated with both empty body weight and adipocyte
      size. However, no differences with regard to DIM and CLA supplementation were
      observed in HF cows. Increased accumulation of phagocytic immune cells, albeit at
      low cell numbers, in nonpregnant, over-conditioned SM heifers might be related to
      larger adipocytes secreting higher amounts of chemoattractant adipokines compared
      with the early lactating cows. In conclusion, the extent of fatness in HF cows
      may not be high enough to stimulate significant infiltration of phagocytic cells
      in AT and, therefore, these immune cells might have no major role in the
      immunologic and metabolic adaptations of AT during early lactation.

PMID- 22612940
TI  - Field evaluation of 2 collar-mounted activity meters for detecting cows in estrus
      on a large pasture-grazed dairy farm.
AB  - This study tested the hypothesis that a commercially available system for
      detecting estrus based on cow activity would perform similarly to that of
      typical, visual assessment of mounting indicators placed on the tail head of the
      cow. The hypothesis was applied to a large, pasture-grazed, seasonal-calving
      dairy herd, and the technology was tested as a stand-alone system. One of 2 types
      of commercially available collar-mounted activity meters was fitted to 635 cows,
      and the activity data collected during the 37-d artificial breeding period were
      analyzed. The first collar-mounted activity meter monitored activity only (AO
      collars), whereas the second meter measured activity and rumination
      characteristics (AR collars). Only activity data were used in the current study.
      Activity-based estrus alerts were initially identified using the default activity
      threshold value recommended by the manufacturer, but a range of activity
      threshold values was then analyzed to determine their effect on estrus detection
      performance. Milk progesterone data and insemination records were used to
      identify gold standard positive (n = 835) and negative (n = 22,660) estrus dates,
      to which activity alerts were compared. Visual assessment of mounting indicators
      resulted in a manual detection performance of 91.3% sensitivity (SN), 99.8%
      specificity (SP), and 94.5% positive predictive value (PPV). The AR collars
      achieved 76.9, 99.4, and 82.4% for SN, SP, and PPV, whereas the AO collars
      achieved 62.4, 99.3, and 76.6% for SN, SP, and PPV, respectively. The observed
      performance of the activity systems may be underestimated due to test design and
      applied assumptions, including determining the date of estrus. Lowering the
      activity threshold from the default value improved sensitivity but the number of
      false positive alerts was considered to become unmanageable from a practical
      perspective as sensitivity reached peak values. Time window analysis, receiver
      operating characteristic curves, and curves of SN and PPV were found to be useful
      in the analysis and interpretation of results. They generate relevant performance
      data that allow for meaningful comparisons between similar studies. Although the
      2 activity systems tested did not perform to the high level of manual estrus
      detection found in this study, the potential exists for these systems to be a
      valuable tool on farms with lower estrus detection performance or for farmers
      managing larger herds.

PMID- 22612941
TI  - Metabolic parameters in transition cows as indicators for early-lactation culling
      risk.
AB  - A retrospective cohort study was performed with the objective of determining
      whether the serum concentrations of nonesterified fatty acids (NEFA), beta
      hydroxybutyric acid (BHBA), or calcium were associated with the risk of culling
      within 60 d in milk (DIM) in Holstein cows, and to establish thresholds for each
      metabolite that were predictive of increased culling risk. Data from 5,979 cows
      in Ontario (Canada) and several US states were obtained from 4 previously
      reported studies. For each metabolite and each of 3 sampling weeks (-1, +1, and
      +2 relative to calving), an optimal threshold was calculated based on having the
      maximum combined sensitivity (Se) and specificity (Sp) and used to categorize the
      serum concentrations into high and low risk groups. Logistic regression models
      were built for each metabolite and each week of sampling, as well as considering
      together all metabolites in wk -1 and wk +1 relative to calving. Cow was
      considered the experimental unit and herd as a random effect. Considered
      separately, precalving NEFA >= 0.4 mmol/L [odds ratio (OR)=1.8; 95% confidence
      interval (CI)=1.4 to 2.2], NEFA >= 0.8 mmol/L in wk +1 relative to calving
      (OR=2.0; 95% CI=1.5 to 2.6) and NEFA >= 0.8 mmol/L in wk +2 (OR=4.2; 95% CI=1.9
      to 9.4 for cows in lactation 2; OR=2.1; 95% CI=1.4 to 3.3 for cows in lactation
      >= 3) were each associated with an increased risk of culling within the first 60
      DIM. Similarly, BHBA >= 0.7 mmol/L in wk -1 (OR=1.8; 95% CI=1.3 to 2.5), BHBA >=
      1.2 mmol/L in wk +1 (OR=1.8; 95% CI=1.4 to 2.2), and BHBA >= 1.6 mmol/L in wk +2
      (OR=3.2; 95% CI=1.6 to 6.4 for cows in lactation 2; OR=2.3; 95% CI=1.6 to 3.3 for
      cows in lactation >= 3) were each associated with an increased risk of culling
      within the first 60 DIM. Likewise, calcium <= 2.3 mmol/L in wk -1 (OR=1.6; 95%
      CI=1.2 to 2.2), calcium <= 2.2 mmol/L in wk +1 (OR=1.5; 95% CI=1.2 to 1.9), and
      calcium <= 2.3 mmol/L in wk +2 (OR=2.3; 95% CI=1.1 to 3.1) were each associated
      with an increased risk of culling within the first 60 DIM. When all metabolites
      were analyzed together, serum NEFA and calcium concentrations in wk -1 and serum
      NEFA concentration in wk +1 remained in the models. In conclusion, elevated serum
      NEFA and BHBA concentrations and lower serum calcium concentrations within 1 wk
      before calving through 2 wk after calving were associated with an increased risk
      of culling in early lactation. Measuring the concentration of selected
      metabolites around parturition may help to develop monitoring and intervention
      strategies to prevent early culling in transition dairy cows.

PMID- 22612942
TI  - Effect of pen size, group size, and stocking density on activity in freestall
      housed dairy cows.
AB  - The purpose was to determine the effects of the physical dimensions of the pen
      and group size and stocking density on cow activity. Cows (randomly assigned to 4
      groups of 6 animals each) were tested in pens with 24 or 12 lying places and in
      groups with 12 or 6 cows. All groups were tested in each of the 4 treatments with
      treatment order allocated using a 4 * 4 Latin square. The distance moved and the
      number of movements were calculated using 5-min scan sampling of video recordings
      over a 48-h period. Time spent lying down, number of lying bouts, and the
      duration of each lying bout were recorded using activity sensors. Displacements
      at the feed bunk were assessed by continuous analysis of video for 3h after the
      delivery of the fresh feed in the afternoon. Cows moved greater distances when
      kept in a large versus small pens (330.2 vs. 270.1 +/- 11.6 m/d; mean +/- SE),
      irrespective of group size. Cows moved more often when kept in the larger pen
      (21.3 vs. 19.2 +/- 0.63% of scans). The time spent lying down decreased when
      density increased (59.1 vs. 55.8 +/- 2.3% of scans at 25% and 100% stocking,
      respectively). Treatment had no effect on the number of displacements at the feed
      bunk. Physical dimensions of the pen play an important role in how much cows
      move, and stocking density affects lying time.

PMID- 22612943
TI  - Description and typology of intensive Chios dairy sheep farms in Greece.
AB  - The aim was to assess the intensified dairy sheep farming systems of the Chios
      breed in Greece, establishing a typology that may properly describe and
      characterize them. The study included the total of the 66 farms of the Chios
      sheep breeders' cooperative Macedonia. Data were collected using a structured
      direct questionnaire for in-depth interviews, including questions properly
      selected to obtain a general description of farm characteristics and overall
      management practices. A multivariate statistical analysis was used on the data to
      obtain the most appropriate typology. Initially, principal component analysis was
      used to produce uncorrelated variables (principal components), which would be
      used for the consecutive cluster analysis. The number of clusters was decided
      using hierarchical cluster analysis, whereas, the farms were allocated in 4
      clusters using k-means cluster analysis. The identified clusters were described
      and afterward compared using one-way ANOVA or a chi-squared test. The main
      differences were evident on land availability and use, facility and equipment
      availability and type, expansion rates, and application of preventive flock
      health programs. In general, cluster 1 included newly established, intensive,
      well-equipped, specialized farms and cluster 2 included well-established farms
      with balanced sheep and feed/crop production. In cluster 3 were assigned small
      flock farms focusing more on arable crops than on sheep farming with a tendency
      to evolve toward cluster 2, whereas cluster 4 included farms representing a
      rather conservative form of Chios sheep breeding with low/intermediate inputs and
      choosing not to focus on feed/crop production. In the studied set of farms, 4
      different farmer attitudes were evident: 1) farming disrupts sheep breeding; feed
      should be purchased and economies of scale will decrease costs (mainly cluster
      1), 2) only exercise/pasture land is necessary; at least part of the feed
      (pasture) must be home-grown to decrease costs (clusters 1 and 4), 3) providing
      pasture to sheep is essential; on-farm feed production decreases costs (mainly
      cluster 3), and 4) large-scale farming (feed production and cash crops) does not
      disrupt sheep breeding; all feed must be produced on-farm to decrease costs
      (mainly cluster 3). Conducting a profitability analysis among different clusters,
      exploring and discovering the most beneficial levels of intensified management
      and capital investment should now be considered.

PMID- 22612944
TI  - Consequences of physiological heat shock beginning at the zygote stage on
      embryonic development and expression of stress response genes in cattle.
AB  - The goal was to understand the role of heat shock at the zygote stage in causing
      infertility. Culture at 40 degrees C reduced the percentage of inseminated
      oocytes that became a morula or blastocyst by d 6 or that were a blastocyst at d
      8. An additional experiment was done to test whether effects of heat shock occur
      early in development or at the time of morula formation. Exposure to 40 degrees C
      for 24 h decreased development to the blastocyst stage if exposure was at the
      zygote stage [8 to 32 h postinsemination (hpi)] but not if exposure occurred at
      the morula stage (116 to 140 hpi). To test effect of oxygen concentration,
      inseminated oocytes were cultured at 40 degrees C for 12 or 24 h in either air
      (20.95% O2; high oxygen) or a 5% (vol/vol) O2 environment (low oxygen) that
      approximates the partial oxygen pressure of the reproductive tract. Blastocyst
      development was reduced by 40 degrees C for 12 or 24 h under both atmospheres and
      was higher for embryos cultured in low oxygen than for embryos cultured in high
      oxygen. Examination of cell numbers at 72 hpi indicated that heat shock reduced
      developmental potential of embryos by reducing competence to complete cleavage
      divisions after first cleavage. Changes in expression of genes involved in heat
      shock and oxidative stress were measured to determine whether zygotes are more
      susceptible to heat shock because of reduced capacity for transcription. Heat
      shock was performed for 24 h at the 1-cell stage (expression examined in 2-cell
      embryos) or at d 5 (examined in morulae). Heat shock increased amounts of steady
      state mRNA for HSPA1A but not for HSP90AA, SOD1, or CAT. We observed a tendency
      for a stage * temperature interaction for HSPA1A because the difference in
      expression between 38.5 and 40 degrees C was greater for morulae than for 2-cell
      embryos. The amount of HSPA1A mRNA was less for morulae that were heat shocked
      than for 2-cell embryos cultured at 38.5 degrees C. Heat shock at a temperature
      and oxygen tension similar to those seen in vivo can disrupt developmental
      competence of bovine zygotes. Increased susceptibility of the early embryo
      compared with the morula to heat shock was not due to reduced HSPA1A mRNA because
      amounts were higher for 2-cell embryos than for morulae.

PMID- 22612945
TI  - Progesterone supplementation postinsemination improves fertility of cooled dairy
      cows during the summer.
AB  - Reduced fertility of dairy cows during periods of elevated temperature, humidity,
      or both might be associated with low plasma progesterone concentration.
      Alleviation of thermal stress by efficient cooling is a prerequisite for
      improving fertility by hormonal treatment. We examined whether insertion of a
      controlled intravaginal drug-releasing (CIDR) insert containing progesterone
      following artificial insemination (AI) would improve summer conception rate.
      Control (n = 195) and treated (CIDR; n=165) cows, yielding on average 42.3 kg
      milk/d, were inseminated following estrus detection during the summer (July to
      October) in 2 commercial dairy herds in Israel. Mean maximal air temperature and
      relative humidity during the study were 30.2 degrees C and 86%, respectively. All
      experimental cows were efficiently cooled throughout the study, as confirmed by
      measuring the body temperature of random cows. Treated cows received a CIDR
      insert on d 5 +/- 1 post-AI for 13 d and pregnancy was confirmed by palpation 45
      d post-AI. Plasma progesterone concentration in treated cows was elevated by
      approximately 1.5 ng/mL. Multiple logistic regressions were used to analyze
      conception rate. Treatment did not alter the overall conception rate; however,
      probability of conception increased in CIDR-treated cows with low body condition
      score (BCS) compared with their control counterparts (53 vs. 27%, respectively).
      A pronounced increase in probability of conception was recorded in CIDR-treated
      cows exhibiting both low BCS and postpartum reproductive disorders, compared with
      their control counterparts (58 vs. 14%, respectively). Exogenous progesterone
      supplementation on d 5 post-AI for 13 d improves summer fertility of
      subpopulations of cows exhibiting low BCS and postpartum reproductive disorders.
      Reproductive management based on specific hormonal treatment of designated
      subgroups of cows known to derive beneficial effects from it might improve
      treatment efficiency and reduce expenses.

PMID- 22612946
TI  - The effect of intrauterine administration of mannose or bacteriophage on uterine
      health and fertility of dairy cows with special focus on Escherichia coli and
      Arcanobacterium pyogenes.
AB  - The objective of this study was to evaluate the effects of intrauterine
      administration of 50 g of ultrapure mannose or a bacteriophage cocktail and the
      presence of Escherichia coli and Arcanobacterium pyogenes in the uterine lumen on
      uterine health and reproductive performance of lactating dairy cows. The study
      was conducted on a commercial dairy farm located near Ithaca, New York, from May
      4 to January 20, 2011, and 597 cows were enrolled. The cows were divided randomly
      into 3 treatment groups, and treatments were administered at 2 +/- 1 d in milk
      (DIM). Treatment 1 consisted of intrauterine administration of 50 g of ultrapure
      mannose powder divided in 4 pills; treatment 2 consisted of intrauterine
      administration of a bacteriophage cocktail that included 4 different phages in
      one pill, with a dose of approximately 107 plaque-forming units; and treatment 3
      consisted of intrauterine administration of one empty pill (control).
      Intrauterine fluid swabs were collected on day of treatment and at 10 +/- 3 DIM;
      uterine lavage samples were collected at 35 +/- 3 DIM. Swabs and uterine lavage
      samples were cultured for E. coli and A. pyogenes. The intrauterine
      administration of mannose and bacteriophage did not affect uterine health,
      reproduction performance, or outcome of intrauterine secretion cultures for E.
      coli and A. pyogenes. Prevalence of intrauterine E. coli at 2 +/- 1 DIM and A.
      pyogenes at 2 +/- 1, 10 +/- 3, and 35 +/- 3 were affected by retained placenta.
      Additionally, prevalence of intrauterine E. coli at 10 +/- 3 and A. pyogenes at
      35 +/- 3 DIM were associated with metritis, and cows that were diagnosed with
      clinical endometritis at 35 +/- 3 DIM had greater prevalence of intrauterine E.
      coli at 2 +/- 1 DIM and A. pyogenes at 35 +/- 3 DIM. Furthermore, cows positive
      for E. coli at 2 +/- 1 and 10 +/- 3 DIM and for A. pyogenes at 10 +/- 3 DIM had
      1.63, 2.34, and 1.54 increased odds of having metritis. Cows positive for A.
      pyogenes at 35 +/- 3 DIM and for E. coli at 2 +/- 1 DIM had 19.8 and 2.66 higher
      odds of being diagnosed with clinical endometritis, respectively. Additionally,
      cows negative for E. coli at 2 +/- 1 DIM were 1.39 times more likely to conceive
      than cows positive cows for E. coli.

PMID- 22612947
TI  - Epidemiology of coagulase-negative staphylococci intramammary infection in dairy
      cattle and the effect of bacteriological culture misclassification.
AB  - Objectives of this study were to identify the manageable risk factors associated
      with the lactational incidence, elimination, and prevalence of coagulase-negative
      staphylococci (CNS) intramammary infections (IMI) while taking into account the
      difficulties inherent to their diagnosis. A second objective was to evaluate the
      effect of CNS IMI misclassification in mastitis research. A cohort of 90 Canadian
      dairy herds was followed throughout 2007 to 2008. In each herd, series of quarter
      milk samples were collected from a subsample of cows and bacteriological culture
      was performed to identify prevalent, incident, and eliminated CNS IMI. Practices
      used on farms were captured using direct observations and a validated
      questionnaire. The relationships between herd CNS IMI prevalence and herd
      incidence and elimination rates were explored using linear regression. Manageable
      risk factors associated with the prevalence, incidence, or elimination of CNS IMI
      were identified via Bayesian analyses using a latent class model approach,
      allowing adjustment of the estimates for the imperfect sensitivity and
      specificity of bacteriological culture. After adjustment for the diagnostic test
      limitations, a mean CNS IMI quarter prevalence of 42.7% [95% confidence interval
      (CI): 34.7, 50.1] and incidence and elimination rates of 0.29 new IMI/quarter
      month (95% CI: 0.21, 0.37) and 0.79 eliminated IMI/quarter-month (95% CI: 0.66,
      0.91), respectively, were observed. Considerable biases of the estimates were
      observed when CNS IMI misclassification was ignored. These biases were important
      for measures of association with risk factors, were almost always toward the null
      value, and led to both type I and type II errors. Coagulase-negative
      staphylococci IMI incidence appeared to be a stronger determinant of herd IMI
      prevalence than IMI elimination rate. The majority of herds followed were already
      using blanket dry cow treatment and postmilking teat disinfection. A holistic
      approach considering associations with all 3 outcomes was used to interpret
      associations between manageable risk factors and CNS IMI. Sand and wood-based
      product bedding showed desirable associations with CNS IMI compared with straw
      bedding. Quarters of cows that had access to pasture during the sampling period
      had lower odds of acquiring a new CNS IMI and of having a prevalent CNS IMI. Many
      practices showed an association with only one of the CNS outcomes and should,
      therefore, be considered with caution.

PMID- 22612948
TI  - Technical note: quantification of plasma 1- and 3-methylhistidine in dairy cows
      by high-performance liquid chromatography-tandem mass spectrometry.
AB  - To improve monitoring of protein mobilization in dairy cows, we developed and
      evaluated a method to quantify 1-methylhistidine and 3-methylhistidine in plasma
      by HPLC-tandem mass spectrometry. The analytical method described is (1)
      sensitive: both histidine derivates can be detected in the picomole range; (2)
      accurate: intra- and interassay coefficients of variation were < 5% for all
      standard solutions of 1-methylhistidine and 3-methylhistidine measured (31 to 500
      pmol); (3) specific: 1-methylhistidine is clearly separated from 3-methyl
      histidine in plasma samples from dairy cows; and (4) flexible: can be easily
      adapted to measure other amino acids or compounds containing a primary amine. 1
      Methylhistidine is present in plasma of dairy cows at concentrations of 5.0 +/-
      1.7 MUM, similar to concentrations of 3-methylhistidine (4.4 +/- 2.4 MUM).
      Analytical separation of both histidine metabolites is essential when plasma 3
      methylhistidine is used as indicator for muscle breakdown in dairy cows. Specific
      quantification of the concentration of 3-methylhistidine in bovine plasma samples
      by HPLC tandem mass spectrometry can improve monitoring of protein mobilization
      in dairy cows.

PMID- 22612949
TI  - Technical note: identification of reference genes for gene expression studies in
      different bovine tissues focusing on different fat depots.
AB  - Selection of stable reference genes (REF) is important in real-time PCR data
      normalization. Bovine tissues such as the mammary gland, liver, muscle, and s.c.
      fat from the tail head have been thoroughly explored for stable REF, whereas
      fewer reports exist for other fat depots. Therefore, a suitable combination of
      REF was tested for different tissues of dairy cattle. Holstein dairy heifers (n =
      25) were supplemented (100 g/d) with a control fat (n = 15) without conjugated
      linoleic acids or with rumen-protected conjugated linoleic acids (n = 10) from
      the day of calving until slaughter at 1, 42, or 105 d postpartum (n = 5, 10, and
      10, respectively). Samples from 6 fat depots (omental, mesenterial,
      retroperitoneal, s.c. tail head, s.c. withers, and s.c. sternum), liver,
      semitendinosus muscle, and mammary gland were collected. The REF mRNA were
      quantified and their stability was analyzed using geNorm(plus). The 3 most stable
      REF in individual fat tissues and muscle were EMD (emerin), POLR2A (RNA
      polymerase II), and LRP10 (lipoprotein receptor-related protein 10); in mammary
      gland were MARVELD1 (marvel domain containing 1), EMD, and LRP10; and in liver
      were HPCAL1 (hippocalcin-like 1), LRP10, and EIF3K (Eukaryotic translation
      initiation factor 3). The 3 most stable REF in s.c. fat were EMD, LRP10, and
      EIF3K; in visceral fat were POLR2A, LRP10, and MARVELD1; and for all 6 adipose
      tissues were LRP10, EIF3K, and MARVELD1. When the mammary gland was added to the
      6 adipose depots, at least 5 REF (LRP10, POLR2A, EIF3K, MARVELD1, and HPCAL1)
      were needed to reach the threshold of 0.15. Addition of liver to the above
      mentioned tissues increased the V value. The data improve the comparison of gene
      expression between different fat depots. In each case, GAPDH had the lowest
      stability value.

PMID- 22612950
TI  - Comparison of the sulfur hexafluoride tracer and respiration chamber techniques
      for estimating methane emissions and correction for rectum methane output from
      dairy cows.
AB  - The objectives of the present study were to compare the sulfur hexafluoride (SF6)
      and respiration chamber techniques for measuring methane (CH4) emissions from
      dairy cows and to determine the proportion of CH4 that is released through the
      rectum. Data used were derived from 20 early lactation dairy cows in a 2 * 2
      factorial design study for 4 periods with 6 wk/period. The 4 treatment diets
      consisted of grass silage and 2 levels of concentrate (30 and 60% dry matter
      basis), with or without yeast supplement. At the end of each period, CH4
      emissions were measured simultaneously using the SF6 and respiration chamber
      techniques when cows were housed in chambers. The SF6 technique was also used
      when cows were housed in digestibility units (barn location) before and after
      respiratory chamber measurements (chamber location). The simultaneous
      measurements in chamber location revealed that CH4 emission estimates by the SF6
      technique were similar to those by the respiration chamber technique in the first
      3 periods, although the SF6 estimates were significantly higher in period 4. The
      regression of all data from the 4 periods demonstrated a linear relationship
      between the SF6 and respiration chamber measurements for total CH4 emissions
      (g/d, R2 = 0.69) and for CH4 emissions per unit of milk yield (g/kg, R2 = 0.88),
      and a quadratic relationship for CH4 emissions per unit of dry matter intake
      (g/kg, R2 = 0.64). The CH4 emissions from the rectum were calculated as the
      difference between CH4 estimates from the SF6 technique when cows were housed in
      respiratory chambers and barn locations, which was 3% of the total CH4 emissions
      from the mouth, nostrils, and rectum. The SF6 estimates in the chamber location
      accounted for all sources of emissions, whereas those in the barn location, like
      that in grazing conditions, did not include CH4 emission from the rectum.
      Therefore, the SF6 measurements for grazing cattle should be adjusted for CH4
      emissions from the rectum (3% of total). We conclude that the SF6 technique is
      reasonably accurate for estimating CH4 emissions.

PMID- 22612951
TI  - Effects of feeding different linseed sources on omasal fatty acid flows and fatty
      acid profiles of plasma and milk fat in lactating dairy cows.
AB  - The aim of this experiment was to study the effects of feeding different linseed
      sources on omasal fatty acid (FA) flows, and plasma and milk FA profiles in dairy
      cows. Four ruminally cannulated lactating Holstein-Friesian cows were assigned to
      4 dietary treatments in a 4*4 Latin square design. Dietary treatments consisted
      of supplementing crushed linseed (CL), extruded whole linseed (EL), formaldehyde
      treated linseed oil (FL) and linseed oil in combination with marine algae rich in
      docosahexaenoic acid (DL). Each period in the Latin square design lasted 21 d,
      with the first 16 d for adaptation. Omasal flow was estimated by the omasal
      sampling technique using Cr-EDTA, Yb-acetate, and acid detergent lignin as
      digesta flow markers. The average DM intake was 20.6 +/- 2.5 kg/d, C18:3n-3
      intake was 341 +/- 51 g/d, and milk yield was 32.0 +/- 4.6 kg/d. Milk fat yield
      was lower for the DL treatment (0.96 kg/d) compared with the other linseed
      treatments (CL, 1.36 kg/d; EL, 1.49 kg/d; FL, 1.54 kg/d). Omasal flow of C18:3n-3
      was higher and C18:3n-3 biohydrogenation was lower for the EL treatment (33.8
      g/d; 90.9%) compared with the CL (21.8 g/d; 94.0%), FL (15.5 g/d; 95.4%), and DL
      (4.6 g/d; 98.5%) treatments, whereas whole-tract digestibility of crude fat was
      lower for the EL treatment (64.8%) compared with the CL (71.3%), FL (78.5%), and
      DL (80.4%) treatments. The proportion of C18:3n-3 (g/100 g of FA) was higher for
      the FL treatment compared with the other treatments in plasma triacylglycerols
      (FL, 3.60; CL, 1.22; EL, 1.35; DL, 1.12) and milk fat (FL, 3.19; CL, 0.87; EL,
      0.83; DL, 0.46). Omasal flow and proportion of C18:0 in plasma and milk fat were
      lower, whereas omasal flow and proportions of biohydrogenation intermediates in
      plasma and milk fat were higher for the DL treatment compared with the other
      linseed treatments. The results demonstrate that feeding EL did not result in a
      higher C18:3n-3 proportion in plasma and milk fat despite the higher omasal
      C18:3n-3 flow. This was related to the decreased total-tract digestibility of
      crude fat. Feeding FL resulted in a higher C18:3n-3 proportion in plasma and milk
      fat, although the omasal C18:3n-3 flow was similar or lower than for the CL and
      EL treatment, respectively. Feeding DL inhibited biohydrogenation of trans-11,cis
      15-C18:2 to C18:0, as indicated by the increased omasal flows and proportions of
      biohydrogenation intermediates in plasma and milk fat.

PMID- 22612952
TI  - On-farm methane measurements during milking correlate with total methane
      production by individual dairy cows.
AB  - The objective of this study was to investigate whether measurement of methane
      emissions by individual dairy cows during milking could provide a useful
      technique for monitoring on-farm methane emissions. To quantify methane emissions
      from individual cows on farm, we developed a novel technique based on sampling
      air released by eructation during milking. Eructation frequency and methane
      released per eructation were used to estimate methane emission rate. For 82 cows,
      methane emission rate during milking increased with daily milk yield (r = 0.71),
      but varied between individuals with the same milk yield and fed the same diet.
      For 12 cows, methane emission rate recorded during milking on farm showed a
      linear relationship (R2 = 0.79) with daily methane output by the same cows when
      housed subsequently in respiration chambers. For 42 cows, the methane emission
      rate during milking was greater on a feeding regimen designed to produce high
      methane emissions, and the increase compared with a control regimen was similar
      to that observed for cows in respiration chambers. It was concluded that, with
      further validation, on-farm monitoring of methane emission rate during milking
      could provide a low-cost reliable method to estimate daily methane output by
      individual dairy cows, which could be used to study variation in methane, to
      identify cows with low emissions, and to test outcomes of mitigation strategies.

PMID- 22612953
TI  - Variation among individual dairy cows in methane measurements made on farm during
      milking.
AB  - The objective of this study was to quantify on-farm variation between and within
      cows in methane emissions measured during milking, and to determine which factors
      are related to this variation. Methane emission rate during milking (MERm) was
      recorded at milking using methane analyzers installed in automatic (robotic)
      milking stations for 215 cows over a period of 5 mo. Between-cow variation in
      MERm (mean 2.07, SD 0.629 g/min), was greater than within-cow variation and was
      related to variation in body weight, milk yield, parity, and week of lactation.
      Estimation of daily methane emissions from MERm data, using an equation derived
      from comparisons with respiration chamber data, produced estimates that ranged
      from 278 to 456 g of CH4/d and were commensurate with values predicted from
      metabolizable energy requirements for observed body weight and milk yield. It is
      concluded that methane emissions vary considerably between dairy cows housed
      under commercial conditions. This variation needs to be taken into account when
      performing inventories or testing mitigation strategies, but it might offer
      opportunities for genetic selection.

PMID- 22612954
TI  - Effects of early rumen development and solid feed composition on growth
      performance and abomasal health in veal calves.
AB  - The experiment was designed to study the importance of early rumen development
      and of the composition of solid feed intake on growth performance and abomasal
      health in milk-fed veal calves. One hundred and six Holstein-Friesian male calves
      were included in the experiment, and studied during 2 successive 12-wk periods
      (period 1 and period 2). In a 2 * 2 factorial arrangement, effects of partially
      replacing milk replacer by solid feed during period 1 and partially replacing dry
      matter (DM) intake from maize silage and barley straw by concentrate during
      period 2 were tested. Solid feed during period 1 consisted of maize silage,
      barley straw, and concentrate (25:25:50 on a DM basis). Solid feed during period
      2 consisted of maize silage and barley straw (50:50 ratio on DM basis) for the
      nonconcentrate groups, and maize silage, barley straw and concentrates (25:25:50
      on a DM basis) for the concentrate groups. At the end of period 1 (n=16) and at
      the end of period 2 (n=90), parameters of animal performance, rumen development,
      rumen fermentation, ruminal drinking, and abomasal damage were examined.
      Partially replacing milk replacer by solid feed during period 1 resulted in early
      rumen development (ERD) at the end of period 1, characterized by increased rumen
      weight, and an increased epithelial and absorptive surface area. Both ERD and
      partially replacing roughage by concentrates in period 2 increased the rumen
      development score at the end of period 2. Although ERD calves consumed more solid
      feed and less milk replacer during period 1 and 2 than non-ERD calves, carcass
      weight gains at 25 wk were identical, and utilization of the solid feed provided
      appeared similar to that of milk replacer. Partially replacing roughage by
      concentrates in period 2 increased dressing percentage and warm carcass weight.
      Plaque formation at the rumen mucosa was unaffected by ERD or partially replacing
      roughage by concentrates and generally low in all calves. The prevalence of large
      scars in the abomasum in ERD calves was decreased compared with non-ERD calves.
      This may indicate that ERD provided protection against abomasal lesions. In
      conclusion, early compared with late rumen development improves feed utilization
      and may be beneficial for abomasal health.

PMID- 22612955
TI  - Energy efficiency and its relationship with milk, body, and intake traits and
      energy status among primiparous Nordic Red dairy cattle.
AB  - Existing variation in energy efficiency and its relationship with milk yield and
      milk composition, body weight and body condition, feed intake, and energy status
      was studied in primiparous Nordic Red dairy cattle with data including 3,752
      weekly records from 145 cows. Energy efficiency was defined as energy conversion
      efficiency (ECE) and as residual energy intake (REI) estimated based on Finnish
      feeding standards (REI1) or from the current data (REI2). The results indicated
      true phenotypic variation in energy efficiency of the cows. The proportion of
      total variance due to the animal was 0.35 for REI1, 0.30 for REI2, and 0.50 for
      ECE. The high efficiency based on ECE was associated with increased mobilization
      of body reserves (r = -0.50) and decreased dry matter intake (r = -0.51). With
      REI as an energy efficiency measure, the increased efficiency was associated with
      a large decrease in feed intake (REI1: r = 0.60; REI2: r = 0.74) without any
      effect on body weight change (REI1: r = 0.13; REI2: r = 0.00). Increased
      efficiency based on ECE and REI1 was associated with increased milk yield (ECE: r
      = 0.58; REI1: r = -0.41). A clear effect of stage of lactation on REI was found,
      which could be caused by true differences in utilization of metabolizable energy
      during lactation. However, it might also be related, in part, to the lack of
      knowledge of the composition of body weight change in the beginning of lactation.

PMID- 22612956
TI  - Rumination and its relationship to feeding and lying behavior in Holstein dairy
      cows.
AB  - The objective of this study was to describe the relationship between rumination
      and feeding and lying behavior in dairy cows. Rumination time was monitored
      electronically using HR-Tags (SCR Engineers Ltd., Netanya, Israel). Feeding time
      and dry matter intake (DMI) were monitored using Insentec feed bins (Insentec BV,
      Marknesse, the Netherlands). All measures were collected in 2-h periods for 42
      mature Holstein cows for a minimum of 9 d in the early dry period. Pearson
      correlation was used to describe associations, among 2-h periods within cow,
      first examining the relationship within a single period, and then modeling how
      this relationship changes when a lag of 2, 4, or 6h was imposed. Periods when
      cows spent more time ruminating were associated with lower feeding times and
      lower DMI (r = -0.71 and r = -0.72, respectively), likely because cows were
      unable to feed and ruminate simultaneously. The correlations with rumination time
      changed from negative to positive when lags of 2, 4, and 6h were modeled (r = 
      0.09, 0.24, and 0.15, and r = -0.16, 0.23, and 0.17 for feeding time and DMI at
      lags of 2, 4, and 6h, respectively). These results indicate that following
      periods of high feeding times and intakes, cows spent more time ruminating. This
      relationship peaks at approximately 4h after feeding. Periods of rumination were
      also associated with time spent lying down. Cows that spent more time ruminating
      per day, spent less time feeding (r = -0.34) and rumination times did not relate
      to DMI (r = 0.11). These data indicate that rumination time can be used to
      estimate within-cow variation in feeding behavior and intake, but daily summaries
      of rumination behavior are a poor indicator of DMI.

PMID- 22612957
TI  - Presence of an older weaned companion influences feeding behavior and improves
      performance of dairy calves before and after weaning from milk.
AB  - In commercial dairy production, calves are typically separated from the dam at a
      young age. This practice may interfere with developmental processes mediated by
      social interactions that occur between the calf, her dam, and older social
      partners. The aim of this study was to test the prediction that calves housed
      with an older weaned companion would show earlier intake of solid feed before
      weaning and higher growth rates during and after weaning compared with calves
      housed with calves of their own age. Forty-five dairy calves were separated from
      their dams and housed individually for approximately 7 d. Afterward, calves were
      assigned to pens composed of groups of either 3 young calves or 2 young calves
      and an older weaned calf. Group pens were equipped with automatic milk, water,
      starter, hay feeders, and scales. Weaning was by gradual reduction of milk volume
      over 5 d, from d 36 to d 40. During the preweaning period (d 1 to d 35), the
      number (8.8 vs. 5.1 +/- 0.5 visits/d per calf) and duration (13.2 vs. 8.2 +/- 1.1
      min/d per calf) of visits to the hay feeder was higher for calves housed with an
      older companion, and calves in this treatment consumed more hay (57.9 vs. 25.6 +/
      4.7 g/d) than did calves housed in groups of similar age. Starter intake did not
      differ between treatments before weaning, but the number of visits (15.2 vs. 9.4
      +/- 0.6 visits/d) and the time spent at the starter feeder (6.5 vs. 3.4 +/- 0.5
      min/d) were higher for calves housed with an older weaned companion. During the
      weaning period (d 36 to d 40), calves housed with an older companion spent more
      time at the starter feeder (22.1 vs. 12.9 +/- 1.9 min/d) and made fewer
      unrewarded visits to the milk feeder (17.0 vs. 26.1 +/- 1.9 visits/d) than did
      calves housed in groups of similar age. During the postweaning period (d 41 to d
      55), calves housed with an older weaned companion spent less time at the hay
      feeder (32.5 vs. 58.5 +/- 5 .5 min/d) and more time at the starter feeder (41.4
      vs. 28.2 +/- 3.7 min/d), and consumed more starter (1.8 vs. 1.3 +/- 0.1 kg/d).
      Calves housed with an older weaned companion gained more weight during the
      preweaning (0.89 vs. 0.76 +/- 0.03 kg/d) and postweaning (1.4 vs. 1.1 +/- 0.05
      kg/d) periods. We conclude that housing young calves with an older weaned
      companion stimulates feeding behavior and growth before and after weaning from
      milk.

PMID- 22612958
TI  - Effect of fat additions to diets of dairy cattle on milk production and
      components: a meta-analysis and meta-regression.
AB  - The objectives of this study were to critically review randomized controlled
      trials, and quantify, using meta-analysis and meta-regression, the effects of
      supplementation with fats on milk production and components by dairy cows. We
      reviewed 59 papers, of which 38 (containing 86 comparisons) met eligibility
      criteria. Five groups of fats were evaluated: tallows, calcium salts of palm fat
      (Megalac, Church and Dwight Co. Inc., Princeton, NJ), oilseeds, prilled fat, and
      other calcium salts. Milk production responses to fats were significant, and the
      estimated mean difference was 1.05 kg/cow per day, but results were
      heterogeneous. Milk yield increased with increased difference in dry matter
      intake (DMI) between treatment and control groups, decreased with predicted
      metabolizable energy (ME) balance between these groups, and decreased with
      increased difference in soluble protein percentage of the diet between groups.
      Decreases in DMI were significant for Megalac, oilseeds, and other Ca salts, and
      approached significance for tallow. Feeding fat for a longer period increased
      DMI, as did greater differences in the amount of soluble protein percentage of
      the diet between control and treatment diets. Tallow, oilseeds, and other Ca
      salts reduced, whereas Megalac increased, milk fat percentage. Milk fat
      percentage effects were heterogeneous for fat source. Differences between
      treatment and control groups in duodenal concentrations of C18:2 and C 18:0 fatty
      acids and Mg percentage reduced the milk fat percentage standardized mean
      difference. Milk fat yield responses to fat treatments were very variable. The
      other Ca salts substantially decrease, and the Megalac and oilseeds increased,
      fat yield. Fat yield increased with increased DMI difference between groups and
      was lower with an increased estimated ME balance between treatment and control
      groups, indicating increased partitioning of fat to body tissue reserves. Feeding
      fats decreased milk protein percentage, but results were heterogeneous. An
      increased number of milkings increased the milk protein percentage, whereas the
      difference between the treatment and control groups in duodenal concentrations of
      18:2 fatty acids and dietary Mg concentration reduced the milk protein
      percentage. None of the fat treatments influenced milk protein production. The
      range of responses to different fats fed approached or exceeded 5 standard
      deviations from the mean and differed in point direction for all variables
      studied, indicating the varied and profound biological effects of fats. Responses
      to fat feeding were highly heterogeneous for all variables studied and
      heterogeneity was present within responses to individual fat groups. The lower
      DMI combined with higher milk and milk fat production showed that fats could
      improve the efficiency of milk production. More studies are required to more
      completely characterize sources of variation in responses to fats.

PMID- 22612959
TI  - Quantifying phytate in dairy digesta and feces: alkaline extraction and high
      performance ion chromatography.
AB  - Development of an analytical method with appropriate combination of extraction
      and quantification approaches for undigested phytate in ruminant feces and
      digesta will advance knowledge of phytate degradation in ruminants and help to
      reduce phosphorus excretion. Established quantification methods give satisfactory
      results for feedstuffs and nonruminant manure but recovery of phytate is
      incomplete for ruminant feces and digesta because of their complex sample matrix
      and low ratio of phytate to inorganic P. The objective was to develop a robust,
      accurate, sensitive, and inexpensive method to extract and quantify phytate in
      feeds, ruminant feces, and digesta. Diets varying in phytate content were fed to
      dairy heifers, dry cows, and lactating cows to generate digesta and fecal samples
      of varying composition to challenge extraction and quantification methods.
      Samples were extracted with 0.5 M HCl or 0.25 M NaOH + 0.05 M EDTA. Acid extracts
      were mixed with 20% NaCl, alkaline extracts were acidified to final pH < 2, and
      then both extracts were clarified with C18 cartridges and 0.2-MUm filters. High
      performance ion chromatography (HPIC) was used to quantify phytate. In feed
      samples, the measured phytate was comparable in alkaline and acid extracts (2,965
      vs. 3,085 MUg/g of DM). In digesta and fecal samples, alkaline extraction yielded
      greater estimates of phytate content than did acid extraction (40.7 vs. 33.6 and
      202.9 vs. 144.4 MUg/g of DM for digesta and fecal samples, respectively).
      Analysis of alkaline extracts by HPIC is usually not possible because of sample
      matrix interferences; acidification and C(18)-cartridge elution of alkaline
      extracts prevented this interference. Pure phytate added to dry samples before
      extraction was almost completely recovered (88 to 105%), indicating high
      extraction efficiency, no adverse effect of extract clean-up procedures, and
      accurate quantification of phytate. The proposed method is rapid, inexpensive,
      robust, and combines the extraction power of NaOH-EDTA with the precision and
      sensitivity of HPIC quantification, allowing accurate quantification of phytate
      in feeds, ruminant digesta, and fecal samples.

PMID- 22612960
TI  - Hypophagic effects of propionate increase with elevated hepatic acetyl coenzyme A
      concentration for cows in the early postpartum period.
AB  - Thirty multiparous lactating dairy cows were used in a randomized block design
      experiment to evaluate factors related to the degree of hypophagia from
      intraruminal infusion of propionate. Cows between 3 and 40 d postpartum at the
      start of the experiment were blocked by calving date and randomly assigned to
      treatment. Treatments were 1.0 mol/L propionic acid or 1.0 mol/L acetic acid
      adjusted to pH 6 with sodium hydroxide and infused at 0.5 mol of volatile fatty
      acid/h from 6h before feeding until 12h after feeding. Propionate infusion
      decreased dry matter intake by 20.0%, total metabolizable energy intake by 22.5%,
      and plasma beta-hydroxybutyrate concentration by 54.3% compared with acetate
      infusion. Effects of treatment on dry matter intake were related to concentration
      of acetyl coenzyme A (CoA) in the liver; hypophagic effects of propionate
      compared with acetate increased as liver acetyl CoA concentration increased.
      Hypophagic effects of propionate are greater for cows with elevated
      concentrations of acetyl CoA in the liver.

PMID- 22612961
TI  - Nutrient demand interacts with forage family to affect digestion responses in
      dairy cows.
AB  - Effects of forage family on dry matter intake (DMI), milk production, ruminal
      pool sizes, digestion and passage kinetics, and chewing activity and the
      relationship of these effects with preliminary DMI (pDMI), an index of nutrient
      demand, were evaluated using 13 ruminally and duodenally cannulated Holstein cows
      in a crossover design with a 14-d preliminary period and two 18-d treatment
      periods. During the preliminary period, pDMI of individual cows ranged from 19.6
      to 29.5 kg/d (mean=25.9 kg/d) and 3.5% fat-corrected milk yield ranged from 24.3
      to 60.3 kg/d (mean=42.1 kg/d). Experimental treatments were diets containing
      either a) alfalfa silage (AL) or b) orchardgrass silage (OG) as the sole forage.
      Alfalfa and orchardgrass contained 42.3 and 58.2% neutral detergent fiber (NDF)
      and 22.5 and 11.4% crude protein, respectively. Forage:concentrate ratios were
      60:40 and 43:57 for AL and OG, respectively; both diets contained approximately
      25% forage NDF and 30% total NDF. Preliminary DMI was determined during the last
      4 d of the preliminary period when cows were fed a common diet and used as a
      covariate. Main effects of forage family and their interaction with pDMI were
      tested by ANOVA. Forage family and its interaction with pDMI did not affect feed
      intake, milk yield, or milk composition. The AL diet increased indigestible NDF
      (iNDF) intake and decreased potentially digestible NDF (pdNDF) intake compared
      with OG. The AL diet increased ruminal pH, digestion rates of pdNDF and starch,
      and passage rates of pdNDF and iNDF compared with OG, which affected ruminal
      digestibility. Passage rate of iNDF was related to pDMI; AL increased iNDF
      passage rate and OG decreased it as pDMI increased. The AL diet decreased ruminal
      pool sizes of pdNDF, starch, organic matter, dry matter, and rumen digesta wet
      weight and volume compared with OG. The AL diet decreased ruminating time per
      unit of forage NDF consumed compared with OG, indicating that alfalfa provided
      less physically effective fiber than orchardgrass. The AL diet, but not OG,
      increased ammonia N, nonammonia nonmicrobial N, and nonammonia N fluxes as pDMI
      increased. Efficiency of microbial protein synthesis was positively related to
      pdNDF passage rate for OG, but not AL. The faster rates of digestion and passage
      for AL compared with OG decreased rumen pool size but did not increase feed
      intake for cows consuming AL. Digestion responses to forage family were affected
      by nutrient demand of cows.

PMID- 22612962
TI  - Rates of particle size reduction and passage are faster for legume compared with
      cool-season grass, resulting in lower rumen fill and less effective fiber.
AB  - Effects of forage family on rates of particle size reduction in, and passage
      from, the rumen and the relationship of these effects with preliminary dry matter
      intake (pDMI) were evaluated using 13 ruminally and duodenally cannulated
      Holstein cows in a crossover design with a 14-d preliminary period and two 18-d
      treatment periods. During the preliminary period, pDMI of individual cows ranged
      from 19.6 to 29.5 kg/d (mean = 25.9 kg/d). Experimental treatments were diets
      containing either a) alfalfa silage (AL) or b) orchardgrass silage (OG) as the
      sole forage. Silages were chopped to 10-mm theoretical length of cut and
      contained 42.3 and 58.2% neutral detergent fiber (NDF) for alfalfa and
      orchardgrass, respectively. Both diets contained approximately 25% forage NDF and
      30% total NDF. Feed, orts, rumen, and duodenal samples were wet sieved to
      fractionate particles above (large) and below (small) 2.36 mm. Indigestible NDF
      (iNDF) was used as a flow marker. Preliminary DMI, an index of nutrient demand,
      was determined during the last 4 d of the preliminary period when cows were fed a
      common diet and used as a covariate. Main effects of forage family and their
      interaction with pDMI were tested by ANOVA. Approximately 75% of the NDF consumed
      was large and 25% was small for both treatments, but cows fed AL consumed more
      iNDF and less potentially digestible NDF (pdNDF) than cows fed OG. The AL diet
      increased the reduction rate (large to small) compared with OG despite less
      rumination per unit of forage NDF for AL than OG, suggesting alfalfa NDF was more
      fragile than orchardgrass NDF. Over 55% of particles in the rumen were below 2.36
      mm for AL and OG, indicating that particle size was not a limiting constraint to
      passage. Passage rates (k(p)) of large iNDF and large pdNDF were similar for AL
      and OG, but AL increased k(p) of large pdNDF and OG decreased it as pDMI
      increased. The AL diet increased k(p) of small iNDF and small pdNDF compared with
      OG, resulting in lower rumen fill for AL than OG. The k(p) of small iNDF and
      small pdNDF were similar within forage family, suggesting buoyancy was not
      limiting passage. The OG diet increased rumen pool size of large NDF compared
      with AL, which likely retained small NDF, contributing to the slower k(p) of
      small iNDF and small pdNDF observed for OG. Particle size reduction was a
      prerequisite to ruminal passage but not a constraint. Selective retention of
      small particles was less for alfalfa than orchardgrass, resulting in lower rumen
      fill and less effective fiber.

PMID- 22612963
TI  - Substitution of starch by soluble fiber and Saccharomyces cerevisiae dose
      response on nutrient digestion and blood metabolites for precision-fed dairy
      heifers.
AB  - The objective of this experiment was to determine the effects of 2 levels of
      dietary starch and the dose at which the effects of yeast culture (YC) derived
      from Saccharomyces cerevisiae (Yea-Sacc1026, Alltech Inc., Nicholasville, KY)
      were maximized based on nutrient total-tract digestibility (AD), N utilization,
      and blood metabolites of precision-fed dairy heifers. A split-plot design with
      starch level as the whole plot and YC dose as subplot was administered in a 4
      period (21 d), 4 * 4 Latin square. Eight Holstein heifers (432.49 +/- 6.81 kg of
      body weight) were allocated to 2 starch treatments (28% starch, high starch, HS,
      or 17% starch, low starch, LS) and to a sequence of YC doses (0, 10, 30, and 50
      g/d). Dry matter (DM) and neutral detergent fiber (NDF) AD were not different
      between HS and LS; however, HS decreased acid detergent fiber (ADF) and increased
      hemicellulose AD. Digestibility of DM and organic matter (OM) increased
      quadratically in response to increasing YC dose. Hemicellulose, NDF, and ADF AD
      increased or tended to increase quadratically with increasing YC dose. No
      significant effects were noted on fecal or urine output between dietary starch
      concentrations; YC decreased wet and dry fecal output corresponding to the effect
      in DM and OM. Apparent N digestibility was greater in the LS group. As YC dose
      increased, fecal N output decreased quadratically and was lowest at 30 g/d YC. A
      corresponding quadratic increase was observed for N retention expressed as a
      percentage of N digested: N output in urine tended to increase with increasing YC
      dose, resulting in no differences in retained N (g/d). Dietary starch
      concentration did not affect blood glucose, triglyceride, creatinine, or lactate
      concentration. However, HS increased plasma urea N concentration. Glucose
      concentration tended to increase quadratically with daily YC dose in both starch
      treatments, with the greatest response at 30 g/d. For triglycerides, dietary
      starch concentration and YC dose interacted, decreasing quadratically in the LS
      group and increasing in the HS group (lowest and highest value for 10 g/d
      respectively). We observed a significant time effect for all blood metabolites
      measured. We conclude that starch level did not affect DM AD, but influenced ADF
      and hemicellulose AD. Yeast culture had the greatest effect on DM, NDF, ADF, and
      hemicellulose AD when added at 30 g/d. Addition of YC influenced glucose and
      triglyceride concentrations differently according to the dietary starch
      concentration of the diet.

PMID- 22612964
TI  - Effects of partially replacing dietary starch with dry glycerol in a lactating
      cow diet on ruminal fermentation during continuous culture.
AB  - The effects of dry glycerol as a partial replacement for dietary starch in a
      lactating cow diet on ruminal fermentation and bacterial protein synthesis were
      evaluated using 4 single-flow, continuous-culture fermentors (ranging from 1,015
      to 1,040 mL in volume). The basal lactating cow diet was formulated to have
      partial contents of dietary starch provided from a corn starch supplement [at
      12.37% diet dry matter (DM)], which was partially or completely replaced by a dry
      glycerol product. Both the corn starch supplement and dry glycerol product
      contained 65% of pure corn starch or glycerol, respectively. The final inclusion
      rate for pure glycerol was at 0, 3, 5, or 8% of DM in the basal diet. The
      experiment was conducted using a 4 * 4 Latin square design with four 9-d periods,
      with the first 6 d for adaptation and last 3 d for sampling. Fermentors were
      inoculated with 1L of ruminal fluid and 25 g of ruminal digesta from a ruminally
      cannulated cow receiving a lactation total mixed ration (16% crude protein, 32%
      neutral detergent fiber, and 25% starch; DM basis). Each fermentor was fed 75 g
      of DM of its respective experimental diet daily in 3 equal portions (at 0800,
      1400, and 2000 h). Liquid dilution rate of the fermentors was maintained at 10%/h
      and solids retention time was set at 24 h. Fermentation fluid and the effluent
      from each fermentor were sampled once daily (at 1330 h) from d 7 to 9 of each
      period and pooled by period. Postprandial ruminal fermentation was studied by
      sampling the fermentors hourly for 5 h after the 0800 h feeding on d 9 of each
      period. The total fermentation contents were harvested at the end of the period
      for estimations of bacterial protein synthesis. Replacing corn starch with dry
      glycerol linearly increased the proportions of propionate and valerate at the
      expense of acetate in the fermentation fluid measured daily or for the first 5h
      after feeding. Replacing corn starch with dry glycerol also linearly increased
      the digestibility of dietary neutral detergent fiber without a change on the flow
      or efficiency of bacterial protein synthesis during continuous culture. Results
      indicate that glycerol as a dry product can replace dietary starch as corn starch
      at a level of up to 8% of DM in the diet without negatively affecting ruminal
      fermentation and digestibility during continuous culture.

PMID- 22612965
TI  - Vaccination of pregnant cows with EspA, EspB, gamma-intimin, and Shiga toxin 2
      proteins from Escherichia coli O157:H7 induces high levels of specific colostral
      antibodies that are transferred to newborn calves.
AB  - Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a major cause of intestinal
      disease and hemolytic uremic syndrome, a serious systemic complication that
      particularly affects children. Cattle are primary reservoirs for EHEC O157:H7 and
      the main source of infection for humans. Vaccination of cattle with different
      combinations of bacterial virulence factors has shown efficacy in decreasing EHEC
      O157:H7 shedding. It is, therefore, important to demonstrate whether vaccination
      of pregnant cows with EHEC O157:H7 induces high titers of transferable antibodies
      to avoid early colonization of calves by the bacteria. In this study we evaluated
      the ability of EspA, EspB, the C-terminal fragment of 280 amino acids of gamma
      intimin (gamma-intimin C280) and inactivated Shiga toxin (Stx) 2 proteins to
      induce specific antibodies in colostrum and their passive transference to
      colostrum-fed calves. Friesian pregnant cows immunized by the intramuscular route
      mounted significantly high serum and colostrum IgG responses against EspB and
      gamma-intimin C280 that were efficiently transferred to their calves. Antibodies
      to EspB and gamma-intimin C280 were detected in milk samples of vaccinated cows
      at d 40 postparturition. Significant Stx2-neutralizing titers were also observed
      in colostrum from Stx2-vaccinated cows and sera from colostrum-fed calves. The
      results presented showed that bovine colostrum with increased levels of
      antibodies against EHEC O157:H7 may be obtained by systemic immunization of
      pregnant cows, and that these specific antibodies are efficiently transferred to
      newborn calves by feeding colostrum. Hyperimmune colostrum and milk may be an
      alternative to protect calves from early colonization by EHEC O157:H7 and a
      possible key source of antibodies to block colonization and toxic activity of
      this bacterium.

PMID- 22612966
TI  - Influence of starter protein content on growth of dairy calves in an enhanced
      early nutrition program.
AB  - Our objectives were to determine the effect of starter crude protein (CP) content
      on growth of Holstein calves from birth to 10 wk of age in an enhanced early
      nutrition program, and to compare the enhanced program to a conventional milk
      replacer program. Calves (64 female, 25 male) were assigned to 3 treatments in a
      randomized block design: 1) conventional milk replacer (20% CP, 20% fat) plus
      conventional starter [19.6% CP, dry matter (DM) basis], 2) enhanced milk replacer
      (28.5% CP, 15% fat) plus conventional starter, and 3) enhanced milk replacer plus
      high-CP starter (25.5% CP, DM basis). Calves began treatments (n=29, 31, and 29
      for treatments 1 to 3) at 3 d of age. Conventional milk replacer (12.5% solids)
      was fed at 1.25% of birth body weight (BW) as DM daily in 2 feedings from wk 1 to
      5 and at 0.625% of birth BW once daily during wk 6. Enhanced milk replacer (15%
      solids) was fed at 1.5% of BW as DM during wk 1 and 2% of BW as DM during wk 2 to
      5, divided into 2 daily feedings. During wk 6, enhanced milk replacer was fed at
      1% of BW as DM once daily. Calves were weaned at d 42. Starter was available for
      ad libitum intake starting on d 3. Starter intake was greater for calves fed
      conventional milk replacer. For calves fed enhanced milk replacer, starter intake
      tended to be greater for calves fed enhanced starter. During the weaning period,
      enhanced starter promoted greater starter DM intake than the conventional
      starter. Over the 10-wk study, the average daily gain of BW (0.64, 0.74, and 0.80
      kg/d) was greater for calves fed enhanced milk replacer with either starter and,
      for calves fed enhanced milk replacer, tended to be greater for calves fed high
      CP starter. Rates of change in withers height, body length, and heart girth were
      greater for calves fed enhanced milk replacer but did not differ between starter
      CP concentrations. The postweaning BW for enhanced milk replacer treatments was
      greater for calves receiving the enhanced starter at wk 8 (73.7, 81.3, and 85.8
      kg) and wk 10 (88.0, 94.9, and 99.9 kg). Starter CP content did not affect
      height, length, or heart girth within enhanced milk replacer treatments.
      Regression analysis showed that gain of BW during the first week postweaning (wk
      7) increased with greater 3-d mean starter intake in the week before weaning.
      Starter with 25.5% CP (DM basis) provided modest benefits in starter intake
      (particularly around weaning) and growth for dairy calves in an enhanced early
      nutrition program compared with a conventional starter (19.6% CP).

PMID- 22612967
TI  - Addition of sodium bicarbonate to either 1 or 2 feedings of colostrum replacer:
      effect on uptake and rate of absorption of immunoglobulin G in neonatal calves.
AB  - Forty Holstein dairy calves were blocked by birth date and sex, and randomly
      assigned to 1 of 4 treatments within each block to elucidate the effect of
      feeding regimen and sodium bicarbonate (NaHCO3) supplementation on absorption of
      IgG from colostrum replacer (CR). Calves received CR containing 191.4 g of IgG
      fed either in 1 feeding at 0 h (within 45 min of birth), with or without 30 g of
      NaHCO3, or in 2 feedings (127.6 g of IgG at 0 h, with or without 20 g of NaHCO3,
      and 63.8 g of IgG at 6 h, with or without 10 g of NaHCO3). The treatments were
      (1) 1 feeding of CR+0 g of NaHCO3; (2) 1 feeding of CR+30 g of NaHCO3; (3) 2
      feedings of CR+0 g of NaHCO3; and (4) 2 feedings of CR+30 g total of NaHCO3. Only
      calves born with no dystocia were used on this study. Blood samples were taken at
      0, 6, 12, 18, and 24h postpartum and were analyzed for IgG using a radial
      immunoassay. Results indicated that, individually, feeding regimen and NaHCO3
      treatments had no effect. However, the interaction was significant for 24-h IgG
      and area under the curve, and showed a trend for apparent efficiency of
      absorption. Absorption rate data indicated that, for calves fed within 45 min of
      birth, most IgG absorption occurred in the first 6 h after birth. From 6 to 12 h
      postpartum, IgG absorption started to decrease; however, IgG absorption remained
      higher for calves fed in a single feeding than in 2 feedings. These data
      indicated that NaHCO3 may increase IgG absorption when calves are fed colostrum
      in a single feeding but is not beneficial when colostrum is fed in 2 feedings.

PMID- 22612968
TI  - Lactation performance and digestibility of forages and diets in dairy cows fed a
      hemicellulose extract.
AB  - Inclusion of hemicellulose extract (HE) in cattle diets have shown potential for
      improving fiber digestibility and production efficiency. The objective of this
      research was to evaluate production and digestibility effects of a HE on
      midlactation cows. Twelve multiparous Holstein cows (142 +/- 44 d in milk, 685 +/
      19 kg of body weight) including 4 with ruminal fistula were used in a 2 * 2
      Latin square design with 21-d periods. Cows were fed a control (CON) diet
      containing 55% forage [dry matter (DM) basis, 2/3 corn silage and 1/3 alfalfa
      hay] or a similar diet where 1.0% of the diet DM was replaced with HE (TRT). Dry
      matter intake averaged 27.1 and 26.9 kg/d, for CON and TRT respectively, and was
      not affected by addition of extract. The percentage of milk protein (3.40 vs.
      3.29%) was greater, whereas the percentage of milk fat (3.91 vs. 3.80%) tended to
      be greater, for cows fed the CON compared with the TRT diet. Because of
      numerically greater milk production (38.8 vs. 39.2 kg/d) for cows fed the TRT
      diet, no differences were observed in component yields other than lactose (1.86
      vs. 1.94 kg/d), which tended to be greater for cows fed the TRT ration. Treatment
      improved neutral detergent fiber (NDF) digestibility (38.6 vs. 48.1%) for the TRT
      diet compared with the CON diet but did not affect apparent total-tract DM (67.8
      vs. 68.5%), crude protein (67.2 vs. 67.9%), acid detergent fiber (ADF; 37.1 vs.
      43.3%), or starch (92.8 vs. 92.2%) digestibility. For in situ determinations,
      Dacron bags containing corn silage, alfalfa hay, and either the CON or TRT ration
      were incubated in triplicate in the rumens of the cannulated cows at 0, 3, 6, 9,
      12, 24, and 48 h on d 18 of each period. Each total mixed ration was incubated
      only in cows assigned to the corresponding diet. For corn silage, the rate of
      disappearance of NDF (1.70 vs. 4.27%) and ADF (1.79 vs. 4.66%) increased for cows
      fed the TRT diet. For alfalfa hay, the disappearance of fraction A of DM, NDF,
      and ADF decreased and fraction B of DM and NDF increased with treatment. The rate
      of disappearance for DM (8.03 vs. 11.04%), NDF (6.30 vs. 10.28%), and ADF (5.52
      vs. 9.19%) increased for the alfalfa hay in rumens of treated cows. For the total
      mixed ration, the disappearance of the A fraction of NDF and ADF increased for
      cows fed the TRT diet. Supplementing diets of lactating dairy cows with an HE has
      beneficial effects on fiber degradation characteristics and provides
      opportunities for improving animal performance.

PMID- 22612969
TI  - Effect of a dual-purpose inoculant on the quality and nutrient losses from corn
      silage produced in farm-scale silos.
AB  - This project aimed to determine effects of applying an inoculant containing
      homofermentative and heterofermentative bacteria on the fermentation, nutritive
      value, aerobic stability, and nutrient losses from corn silage produced in farm
      scale silos. Corn forage was harvested at 34% dry matter (DM) and treated without
      (control) or with 5 * 105 cfu/g of Lactobacillus buchneri and Pediococcus
      pentosaceus. The inoculant was sprayed on alternate 8-row-wide swaths of forage,
      and the untreated and inoculated forages were alternately packed into 3.6-m-wide
      bag silos. Forty-five tonnes of corn forage were packed into each of 4 replicate
      bags per treatment and ensiled for 166 d. Silage removed from the bags (500 kg/d)
      was separated into good and spoiled (visibly moldy or darker) silage portions,
      and weighed for 35 d. Weekly composites were analyzed for chemical composition,
      aerobic stability, and fungal counts. Aerobic stability was measured using data
      loggers that recorded sample and ambient temperature every 30 min for 7 d.
      Inoculation did not affect the chemical composition of the spoiled or good silage
      but decreased the quantity (5.7 vs. 12.9 kg/d) and percentage (3.4 vs. 7.8) of
      spoiled silage in the bags by over 50%. Losses of crude protein (0.28 vs. 0.92
      kg/d), gross energy (6.0 * 104 vs. 1.8 * 105 kJ/d), and neutral detergent fiber
      (1.34 vs. 4.12 kg/d) in spoiled silage were less in inoculated versus control
      silages. Inoculated silages had lower pH (3.91 vs. 3.99), lactate concentration
      (7.63 vs. 7.86%), lactate:acetate ratio (1.58 vs. 2.53%), and a greater acetate
      (5.11 vs. 3.56%) concentration than the control silage. Inoculated silages tended
      to have fewer yeasts (2.59 vs. 4.62 log cfu/g) than control silages, but aerobic
      stability was not different across treatments (14.7 vs. 9.5 h). Applying the
      inoculant made the fermentation more heterolactic, inhibited the growth of
      yeasts, and substantially reduced the amount of spoilage and the associated
      energy and nutrient losses.

PMID- 22612970
TI  - Molecular basis of protein structure in combined feeds (hulless barley with
      bioethanol coproduct of wheat dried distillers grains with solubles) in relation
      to protein rumen degradation kinetics and intestinal availability in dairy
      cattle.
AB  - The objectives of this study were to reveal protein molecular structure in
      relation to rumen degradation kinetics and intestinal availability in combined
      feeds of hulless barley with bioethanol coproduct [pure wheat dried distillers
      grains with solubles (DDGS)] at 5 different ratios (100:0, 75:25, 50:50, 25:75,
      and 0:100) in dairy cattle. The parameters assessed included 1) protein chemical
      profiles, 2) protein subfractions partitioned by the Cornell Net Carbohydrate and
      Protein System, 3) in situ protein degradation kinetics, 4) truly absorbed
      protein supply in the small intestine (DVE), metabolizable protein
      characteristics and degraded protein balance (OEB), 5) protein molecular
      structure spectral profiles, and 6) correlation between protein molecular
      structure and protein nutrient profiles and metabolic characteristics. We found
      that 1) with increasing inclusion of wheat DDGS in feed combinations, protein
      chemical compositions of crude protein (CP), neutral detergent-insoluble CP, acid
      detergent-insoluble CP, and nonprotein N were increased, whereas soluble CP was
      decreased linearly; CP subfractions A, B3, and C were increased linearly, but CP
      subfractions B1 and B2 were decreased; truly digestible CP increased but total
      digestible nutrients at 1* maintenance decreased linearly; protein degradation
      rate was decreased without affecting potentially soluble, potentially degradable,
      and potentially undegradable fractions, and both rumen-degradable protein and
      rumen-undegradable protein were increased; by using the DVE/OEB system, the DVE
      and OEB values were increased from 98 to 226 g/kg of dry matter and -1 to 105
      g/kg of dry matter, respectively; 2) by using the molecular spectroscopy
      technique, the spectral differences in protein molecular structure were detected
      among the feed combinations; in the original combined feeds, amide I and II peak
      area and ratio of amide I to II were increased linearly; although no difference
      existed in alpha-helix and beta-sheet height among the combinations, the ratio of
      alpha-helix to beta-sheet height was changed quadratically; 3) in the in situ 48
      h residue samples, amide I and amide II peak area intensities were increased
      linearly and the ratio of amide I to II peak area was decreased linearly from
      4.28 to 2.63; alpha-helix and beta-sheet height of rumen residues were similar
      among 5 feed combinations; and 4) the ratio of alpha-helix to beta-sheet height
      in original feed combinations was strongly correlation with protein chemical and
      nutrient profiles, but the ratio of amide I to II area had no significant
      correlation with all items that were tested; no correlation was found between the
      ratio of alpha-helix to beta-sheet height of the in situ rumen residues and
      protein chemical and nutrient profiles. In conclusion, by integration of hulless
      barley with bioethanol coproduct of wheat DDGS, feed quality in combined feeds
      was improved and more optimized. Adding wheat DDGS increased linearly CP, truly
      digestible CP, rumen-degradable protein, rumen-undegradable protein, DVE, and OEB
      values in combined feeds. The molecular spectral differences of protein molecular
      structures (amide I and II area intensities, the ratio of amide I to amide II,
      and the ratio of alpha-helix to beta-sheet height among feed combinations) were
      detected among the combinations. This may partially explain the biological
      differences in protein chemical profiles and protein utilization and availability
      in dairy cattle. In the original combined feeds, protein alpha-helix-to-beta
      sheet ratio had significant correlations with protein chemical and nutrient
      profiles, but in in situ 48-h residue samples, protein amide I-to-II ratio had
      significant correlations with protein chemical and nutrient profiles. This study
      may provide an insight into how to more efficiently use hulless barley grain
      (high energy and high degradation rate) and wheat DDGS (high metabolizable
      protein and low degradation rate) in beef and dairy production systems.

PMID- 22612971
TI  - Short communication: effects of bedding quality on the lying behavior of dairy
      calves.
AB  - The lying behavior of adult cattle is strongly affected by characteristics of the
      lying surface, but no previous work has assessed the effects of lying surface for
      dairy calves. We evaluated how the lying behavior of dairy calves changed when
      calves were provided sawdust-bedded versus concrete lying surfaces, and in
      response to variation in dryness of the sawdust bedding. Five Holstein calves,
      approximately 2-wk old, were individually housed in pens with half of the lying
      surface bedded with kiln-dried sawdust [90% dry matter (DM)] and the other half
      with wet bedding varying in DM at 4 levels (74, 59, 41, and 29%) or bare
      concrete. All calves were tested on all 5 treatments, with treatment order
      assigned using a 5 * 5 Latin square. Total lying time averaged 17.2 +/- 0.1 h/d
      and did not vary with treatment, but time lying on the wet bedding decreased from
      5.3 +/- 1.1 h/d at 74% DM to almost zero at 29%. Lying times on the side of the
      pen with dry bedding varied from 12.2 +/- 1.2 h/d (when the wet bedding was 74%
      DM) to 16.8 +/- 1.2 h/d (at 29% DM). Standing times were higher on the dry than
      the wet bedding (2.6 vs. 1.7 +/- 0.1 h/d) but did not change across the range of
      bedding DM tested on the wet side. No calves ever lay down on the bare concrete.
      In conclusion, dairy calves showed clear preference for drier sawdust bedding and
      aversion to concrete lying surfaces, indicating that access to soft and dry
      bedding is important for growing calves.

PMID- 22612972
TI  - Technical note: quantification of zeins from corn, high-moisture corn, and corn
      silage using a turbidimetric method: comparative efficiencies of isopropyl and
      tert-butyl alcohols.
AB  - Zeins are corn endosperm storage proteins that encapsulate starch granules into a
      protein matrix, which can act as a barrier to starch accessibility and digestion.
      Laboratory methods to quantify zein are seldom used because they are considered
      arduous and time-consuming. A recently published rapid turbidimetric method (mTM)
      was reinvestigated by changing the solution originally used for the zein
      solubilization step. In particular, the aim was to explore whether, and to what
      extent, the use of tert-butyl alcohol (t-BuOH-mTM) in lieu of isopropyl alcohol
      (i-PrOH-mTM) was able to improve the quantification of zeins from dry corn, high
      moisture corn, and corn silage samples. The nature of the alcohol influenced the
      zein extraction values, and t-BuOH-mTM gave higher zein values in corn (3.6 vs.
      3.3 g/100 g of dry matter) and corn silage samples (1.2 vs. 0.9 g/100 g of dry
      matter) compared with i-PrOH-mTM. In contrast, similar zein extraction values
      were obtained for high-moisture corn (2.1 vs. 1.9 g/100 g of dry matter,
      respectively). Sodium dodecyl sulfate-PAGE analysis revealed no contamination by
      nonzein proteins with the use of tert-butyl alcohol. Overall, these findings
      indicated that tert-butyl alcohol has a greater ability to solubilize zein
      compared with isopropyl alcohol and thus the t-BuOH-mTM allowed greater
      extraction of zeins. Considering the growing interest of animal nutritionists in
      zein proteins, such results should provide useful information for routine
      laboratory analysis.

PMID- 22612973
TI  - Prediction of genomic breeding values for dairy traits in Italian Brown and
      Simmental bulls using a principal component approach.
AB  - The large number of markers available compared with phenotypes represents one of
      the main issues in genomic selection. In this work, principal component analysis
      was used to reduce the number of predictors for calculating genomic breeding
      values (GEBV). Bulls of 2 cattle breeds farmed in Italy (634 Brown and 469
      Simmental) were genotyped with the 54K Illumina beadchip (Illumina Inc., San
      Diego, CA). After data editing, 37,254 and 40,179 single nucleotide polymorphisms
      (SNP) were retained for Brown and Simmental, respectively. Principal component
      analysis carried out on the SNP genotype matrix extracted 2,257 and 3,596 new
      variables in the 2 breeds, respectively. Bulls were sorted by birth year to
      create reference and prediction populations. The effect of principal components
      on deregressed proofs in reference animals was estimated with a BLUP model.
      Results were compared with those obtained by using SNP genotypes as predictors
      with either the BLUP or Bayes_A method. Traits considered were milk, fat, and
      protein yields, fat and protein percentages, and somatic cell score. The GEBV
      were obtained for prediction population by blending direct genomic prediction and
      pedigree indexes. No substantial differences were observed in squared
      correlations between GEBV and EBV in prediction animals between the 3 methods in
      the 2 breeds. The principal component analysis method allowed for a reduction of
      about 90% in the number of independent variables when predicting direct genomic
      values, with a substantial decrease in calculation time and without loss of
      accuracy.

PMID- 22612974
TI  - Heritability of rectal temperature and genetic correlations with production and
      reproduction traits in dairy cattle.
AB  - Genetic selection for body temperature during heat stress might be a useful
      approach to reduce the magnitude of heat stress effects on production and
      reproduction. Objectives of the study were to estimate the genetic parameters of
      rectal temperature (RT) in dairy cows in freestall barns under heat stress
      conditions and to determine the genetic and phenotypic correlations of rectal
      temperature with other traits. Afternoon RT were measured in a total of 1,695
      lactating Holstein cows sired by 509 bulls during the summer in North Florida.
      Genetic parameters were estimated with Gibbs sampling, and best linear unbiased
      predictions of breeding values were predicted using an animal model. The
      heritability of RT was estimated to be 0.17 +/- 0.13. Predicted transmitting
      abilities for rectal temperature changed 0.0068 +/- 0.0020 degrees C/yr from
      (birth year) 2002 to 2008. Approximate genetic correlations between RT and 305-d
      milk, fat, and protein yields, productive life, and net merit were significant
      and positive, whereas approximate genetic correlations between RT and somatic
      cell count score and daughter pregnancy rate were significant and negative.
      Rectal temperature during heat stress has moderate heritability, but genetic
      correlations with economically important traits mean that selection for RT could
      lead to lower productivity unless methods are used to identify genes affecting RT
      that do not adversely affect other traits of economic importance.

PMID- 22612975
TI  - Breeding objectives for Holstein dairy cattle in Iran.
AB  - Trait-by-trait and multiple trait bioeconomic modeling were used to derive farm
      specific economic weights (EW) for a wide range of traits under different
      production and economic circumstances to define breeding objectives for Holstein
      dairy cattle in Iran. Production parameters and economic data were gathered on 10
      dairy farms from March 2008 to February 2010. The EW (economic values multiplied
      by gene expressions, in US dollars per unit of trait per calf born from sires of
      self-replacing females in planning horizon of 20 yr) were estimated to be $0.15
      per kilogram of milk yield; $1.36 per kilogram of fat yield; -$1.02 per kilogram
      of protein yield; $4.59 per month of longevity; -$1.22 per kilogram of mature cow
      weight; -$105.67 for combined somatic cell score and clinical mastitis; -$1.35
      and -$0.28 for percentage direct and maternal calving difficulties, respectively;
      -$3.98 for percentage direct stillbirth; -$0.76 per day of age at first calving; 
      $0.72 per calving interval day; and $0.91 for percentage 56-d nonreturn rate on
      averages across investigated farms. The coefficient of variation of economic
      weights across the 10 farms was lowest for direct calving difficulty and highest
      for calving interval. The proposed Iranian selection index was compared with
      selection indices of major countries exporting semen to Iran. Average relative
      emphasis for production, durability, and health and reproduction, across all
      exporter countries, was 41, 37.5, and 21.5%, respectively, whereas the respective
      values were 50, 14, and 36% for the Iranian index. Significant differences in
      selection indices may potentially decrease the utility of importation of semen as
      a means of achieving sustainable genetic progress in Iran. Results obtained in
      this study provide important information about economic values of traits that can
      be used to improve the Iranian national progeny testing program as well as
      importation rules for semen to Iran.

PMID- 22612976
TI  - A single nucleotide polymorphism in the acetyl-coenzyme A acyltransferase 2
      (ACAA2) gene is associated with milk yield in Chios sheep.
AB  - The objective of this work was to identify single nucleotide polymorphisms (SNP)
      in the ovine acetyl-coenzyme A acyltransferase 2 (ACAA2) gene and investigate
      their association with milk production traits. Molecular characterization was
      accomplished by sequencing the entire coding region and the 3' and 5'
      untranslated regions (UTR) of the ACAA2 gene from individuals of the Chios sheep
      bred in Cyprus. All exons appeared to be monomorphic except for the last exon,
      for which a single SNP located in the 3' UTR of the gene (HM537015:g.2982T>C) was
      detected. Mixed model association analysis, using SNP data from 318 animals from
      104 paternal half-sib families and first-lactation phenotype and pedigree
      information on 2,405 ewes revealed that this SNP was significantly associated
      with milk yield. The significance of the SNP effect persisted when milk yield
      information up to the third lactation was analyzed. Both alleles at the locus
      segregated at similar frequencies. The T allele was associated with increased
      milk yield and exhibited partial dominant action. Animals with the g.2982TT or
      g.2982CT genotype had significantly higher milk yield than those with the
      g.2982CC genotype, with the g.2982T allele having an additive effect of 13.4 (+/-
      4.7) kg and a dominance effect of 7.9 (+/- 6.1) kg. Based on estimated allelic
      effects and sample allele frequencies, the g.2982T>C SNP explained 10% of the
      additive genetic variance for milk yield. A putative mode of action through
      nutrient metabolism is discussed.

PMID- 22612977
TI  - Genetic relationships among mastitis and alternative somatic cell count traits in
      the first 3 lactations of Swedish Holsteins.
AB  - The objectives of this study were to estimate heritabilities of, and genetic
      correlations among, clinical mastitis (CM), subclinical mastitis (SCM), and
      alternative somatic cell count (SCC) traits in the first 3 lactations of Swedish
      Holstein cows, and to estimate genetic correlations for the alternative traits
      across lactations. Data from cows having their first calving between 2002 and
      2009 were used. The alternative SCC traits were based on information on CM and
      monthly test-day (TD) records of SCC traits of 178,613, 116,079, and 64,474
      lactations in first, second, or third parity, respectively. Sires had an average
      of 230, 165, or 124 daughters in the data (parities 1, 2, or 3, respectively).
      Subclinical mastitis was defined as the number of periods with an SCC >150,000
      cell/mL and without a treatment for CM. Average TD SCC between 5 and 150 d was
      used as a reference trait. The alternative SCC traits analyzed were 1) presence
      of at least 1 TD SCC between 41,000 and 80,000 cell/mL (TD41-80), 2) at least 1
      TD SCC >500,000 cells/mL, 3) standard deviation of log SCC over the lactation, 4)
      number of infection peaks, and 5) average days diseased per peak. The same
      variables in different parities were treated as distinct traits. The statistical
      model considered the effects of herd-year, year, month, age at calving, animal,
      and residual. Heritability estimates were 0.07 to 0.08 for CM, 0.12 to 0.17 for
      SCM, and 0.14 for SCC150. For the alternative traits, heritability estimates were
      0.12 to 0.17 for standard deviation of log SCC, TD SCC >500,000 cells/mL, and
      average days diseased per peak, and 0.06 to 0.10 for TD41-80 and number of
      infection peaks. Genetic correlations between CM with SCM were 0.62 to 0.74, and
      correlations for these traits with the alternative SCC traits were positive and
      very high (0.67 to 0.82 for CM, and 0.94 to 0.99 for SCM). Trait TD41-80 was the
      only alternative trait that showed negative, favorable, genetic correlations with
      CM (-0.22 to -0.50) and SCM (-0.48 to -0.85) because it is associated with
      healthy cows. Genetic correlations among the alternative traits in all 3 parities
      were high (0.93 to 0.99, 0.92 to 0.98, and 0.78 to 0.99, respectively). The only
      exception was TD41-80, which showed moderate to strong negative correlations with
      the rest of the traits. Genetic correlations of the same trait across parities
      were in general positive and very high (0.83 to 0.99). In conclusion, these
      alternative SCC traits could be used in practical breeding programs aiming to
      improve udder health in dairy cattle.

PMID- 22612978
TI  - Effect of CSN1S1-CSN3 (alpha(S1)-kappa-casein) composite genotype on milk
      production traits and milk coagulation properties in Mediterranean water buffalo.
AB  - The aim of this study was to estimate effects of CSN1S1-CSN3 (alpha(S1)-kappa
      casein) composite genotypes on milk production traits and milk coagulation
      properties (MCP) in Mediterranean water buffalo. Genotypes at CSN1S1 and CSN3 and
      coagulation properties [rennet clotting time (RCT), curd firming time (K20), and
      curd firmness (A30)] were assessed by reversed-phase HPLC and computerized
      renneting meter analysis, respectively, using single test-day milk samples of 536
      animals. Alternative protein variants of alpha(S1)-CN and kappa-CN were detected
      by HPLC, and identification of the corresponding genetic variants was carried out
      by DNA analysis. Two genetic variants were detected at CSN1S1 (A and B variants)
      and 2 at CSN3 (X1 and X2 variants). Statistical inference was based on a linear
      model including the CSN1S1-CSN3 composite genotype effect (7 genotypes), the
      effects of herd-test-day (8 levels), and a combined days in milk (DIM)-parity
      class. Composite genotype AB-X2X2 was associated with decreased test-day milk
      yield [-0.21 standard deviation (SD) units of the trait] relative to genotype BB
      X2X2. Genotypes did not affect milk protein content, but genotype AB-X1X1 was
      associated with increased fat content compared with genotype BB-X2X2 (+0.28 SD
      units of the trait) and AB-X1X1 (+0.43 SD units of the trait). For RCT, the
      largest difference (+1.91 min; i.e., 0.61 SD units of the trait) was observed
      between genotype AA-X1X2 and AB-X1X1. Direction of genotype effects on K(20) was
      consistent with that for RCT. The maximum variation in K20 due to genotype
      effects (between AA-X1X2 and AB-X1X1 genotypes) was almost 0.9 SD units of the
      trait. Magnitude of genotype effects was smaller for A30 than for RCT and K20,
      with a maximum difference of 0.5 SD units of the trait between genotype AA-X1X2
      and AA-X1X1. The B allele at CSN1S1 was associated with increased RCT and K20 and
      with weaker curds compared with allele A. Allele X2 at CSN3 exerted opposite
      effects on MCP relative to CSN1S1 B. Because of linkage disequilibrium, allele B
      at CSN1S1 and allele X2 at CSN3 tend to be associated and this likely makes their
      effects cancel each other. This study indicates a role for casein genes in
      variation of MCP of buffalo milk. Further studies are necessary to estimate the
      effects of casein genetic variants on variation of cheese yield.

PMID- 22612979
TI  - Technical note: adjustment of all cow evaluations for yield traits to be
      comparable with bull evaluations.
AB  - Traditional evaluations of cows with genotypes have been adjusted since April
      2010 to be comparable with evaluations of bulls so that their value for
      estimation of single nucleotide polymorphism effects in genomic evaluation
      programs would be improved. However, that adjustment made them not comparable
      with traditional evaluations of nongenotyped cows. To create an adjustment for
      all cows with an evaluation based on US data, Mendelian sampling, which is the
      difference between predicted transmitting ability (PTA) and parent average (PA),
      was calculated for milk, fat, and protein yields and divided by a deregression
      factor. Standard deviations for the deregressed Mendelian sampling (DMS) were
      grouped by reliability with PA contribution removed (REL(no PA)). A
      multiplicative adjustment to reduce the DMS standard deviation for cows so that
      it would be the same as for bulls with similar REL(no PA) was represented as a
      linear function of REL(no PA). Mean cow PA by birth year was subtracted from
      individual bull and cow PA to create within-year PA deviation groups, and mean
      DMS was calculated by PA deviation group. Means decreased for bulls and increased
      for cows with increasing deviation. The differences were fit by linear regression
      on PA deviation and used to adjust cow DMS. The adjustment reduced PTA of cows
      with a high PA and increased PTA of cows with a low PA but did not change
      estimated genetic trend because adjustment was within birth year. The adjustment
      also reduced variance of cow evaluations within birth year. Traditional
      evaluations of genotyped cows with a REL(no PA) of >=55% were further adjusted so
      that the difference between those evaluations and direct genomic values
      calculated using only bulls as predictors was similar to that for bulls. The
      second adjustment was small compared with a 2010 adjustment and, therefore, had
      little effect on the comparability of evaluations for genotyped and nongenotyped
      cows. Cows with converted evaluations from other countries were excluded from the
      predictor population, and their converted evaluations were adjusted so that the
      difference between their mean PTA and direct genomic value was the same as the
      corresponding difference for bulls. For cows with converted evaluations, the
      adjustment amount differed depending on REL(no PA) (<55% or >=55%). The new
      adjustment was implemented by USDA in April 2011 and permits a fairer comparison
      of estimated genetic merit between nongenotyped and genotyped cows.

PMID- 22612981
TI  - Effect of nitrogen content and additional straw on changes in chemical
      composition, volatile losses, and ammonia emissions from dairy manure during long
      term storage.
AB  - Twelve 200-L barrels were used to determine the effects of N content and straw
      addition on changes in chemical composition and volatile losses measured by mass
      balance of dairy manure during a 136-d storage period. In addition, on d 0, 3, 6,
      12, 28, 56, and 136, rate of NH3-N emission was measured, and core samples were
      collected to characterize fermentation pattern. High N (3.06% N, HN) and low N
      (2.75% N, LN) manures were obtained from cows fed diets with 17.2 and 15.2% crude
      protein (dry matter basis), respectively. On d 0, manure scraped from a freestall
      barn floor was diluted with water to 10% dry matter and loaded in barrels with
      (+S) or without (-S) mixing 22g of chopped wheat straw per kilogram of undiluted
      manure. Data were analyzed as a randomized complete block with a 2*2 factorial
      arrangement of treatments and 3 replications. We observed no interaction between
      treatments for the reported measurements, but several day-of-storage by treatment
      interactions were found. Throughout storage, total NH3-N (TAN, NH3-N + NH4+-N;
      71.9 vs. 104.3 mg/dL), pH (6.40 vs. 6.74), and total volatile fatty acids (TVFA,
      starting on d 12) were lower for LN relative to HN manure. In the presence of
      straw, crust formation occurred between d 12 and 28, and pH became lower and TVFA
      became higher starting on d 56, compared with no straw. Treatments did not
      influence loss of organic matter, organic N, organic C, or N, which averaged 31,
      29, 26, and 20%, respectively. However, neutral detergent fiber loss was 44%
      higher for +S relative to -S manure. Consistent reductions in the C:N ratio
      indicated proportionally higher volatile C loss than volatile N loss during
      storage. Overall rate of NH3-N emission was 36% lower for LN than for HN manure.
      In the presence of straw, rate of NH3-N emission did not differ until after crust
      formation, but was 67% lower on d 56 and 95% lower on d 136, when it was barely
      detectable, compared with manure with no straw. Manure pH was highly correlated
      with TVFA:TAN ratio (r=-0.78), and rate of NH3-N emission was correlated with pH,
      TVFA:TAN, TVFA, and TAN (r=0.47, -0.44, -0.23, and 0.28, respectively). In this
      trial, both microbial fermentation and crust formation influenced NH3-N emission
      rate and other measured responses, highlighting the importance of long-term
      sampling to evaluate treatment effects in manure storage studies.

PMID- 22612980
TI  - Susceptibility of coagulase-negative staphylococci to a kanamycin and cefalexin
      combination.
AB  - A combination of kanamycin and cefalexin was licensed in Europe in 2008 to treat
      bovine clinical mastitis. Preliminary broth and disk clinical breakpoints for
      this antibiotic combination have been proposed for Staphylococcus aureus,
      Streptococcus dysgalactiae, Streptococcus uberis, and Escherichia coli. This
      study indicates that these proposed breakpoints also hold for coagulase-negative
      staphylococci (CNS), a group of bacteria frequently isolated in milk samples from
      cows with clinical mastitis. The data show that clinical bovine mastitis isolates
      of CNS from Europe have a high degree of susceptibility to the
      kanamycin/cefalexin combination, with minimal resistance to either agent alone.
      The use of the available kanamycin and cefalexin combination disk for testing the
      susceptibility of bovine mastitis isolates of Staph. aureus, Strep. uberis,
      Strep. dysgalactiae, and E. coli is also reliable for use in the testing of CNS,
      as disk results correlated with broth minimum inhibitory concentrations. The
      study reports, for the first time, the approved Clinical Laboratory Standards
      Institute quality control ranges for the kanamycin/cefalexin combination and wild
      type cutoff values for major bacterial pathogens implicated in bovine mastitis.

PMID- 22612982
TI  - A query for effective mean particle size in dry and high-moisture corns.
AB  - The objective of this study was to investigate whether prediction of fermentation
      potential (FP) of dry and high-moisture (HM) corns could be improved by using a
      concept of effective (e) mean particle size (MPS). A set of FP standards was
      created by processing a single lot of Reid Yellow Dent (RYD) corn to achieve MPS
      of 3,778, 2,786, 2,282, 1,808, 1,410, 806, 586, 378, 308, 226, and 105 MUm. In
      vitro gas production of RYD standards was measured, and peak absolute rate (PAR)
      of gas production (mL/0.2 g of DM/h) was used to establish a standard
      relationship between PAR and MPS. To identify factors other than MPS affecting
      FP, the MPS and nutrient composition of 36 diverse samples of dry (n=18) and HM
      (n=18) corns were determined. Composition included dry matter (DM), crude
      protein, soluble crude protein, neutral detergent fiber, starch, NH3-N, prolamin
      protein, and fat. In vitro gas production of undried, unground dry and HM corns
      was measured, and PAR, time of peak absolute rate (h), maximum cumulative gas
      production (mL/0.2 g of DM), gas production fractional rate (h-1), and lag (h)
      were determined. Nonlinear relationships between MPS, defined as the dependent
      variable, and PAR, as an independent variable, were used to identify FP
      deviations unexplained by MPS. When no variation in nutritional composition was
      present (RYD standards), the relationship between PAR and MPS was described by an
      exponential decay model [RYD_MPS=9,006 * e((-0.452 * PAR)); R2=0.96]. For diverse
      dry and HM corn populations, the variation in MPS explained by PAR was diminished
      (R2=0.50). To investigate factors that diminish the relationship between MPS and
      PAR in diverse corns, relative residual (rr) MPS was determined [rrMPS = (MPS -
      RYD_MPS)/MPS], where RYD_MPS was predicted from the PAR of diverse dry and HM
      corn. The rrMPS was most highly related to prolamin protein [rrMPS(dry)=0.58-0.15
      * (prolamin protein, % of DM); R2=0.43] and NH3-N [rrMPS(HM)=0.21+0.08 * (NH3-N,
      % of total N); R2=0.46] for dry and HM corns, respectively. An eMPS was
      calculated as eMPS = MPS - MPS * rrMPS, where rrMPS was predicted from prolamin
      protein or NH3-N concentration in dry and HM corn, respectively. The natural
      logarithm of eMPS accounted for 84% of the variability in PAR and 53% of the
      variability in the fractional rate of gas production. Calculating eMPS by
      adjusting the MPS of dry corn for prolamin and HM corn for NH3-N concentration
      improved the assessment of industry corn FP.

PMID- 22612983
TI  - A clinical algorithm for efficient, high-resolution cytogenomic analysis of
      uncultured perinatal tissue samples.
AB  - PURPOSE: Cytogenetic analysis of solid tissue is indispensable in perinatal care,
      reproductive planning, and detection of gestational trophoblastic disease.
      Unfortunately, methods in common use suffer from drawbacks including culture
      artifact, low resolution, and high cost. We propose a new diagnostic algorithm
      based on direct genetic analysis of tissues (without cell culture) using QF-PCR
      and array CGH. METHODS: Study samples consisted of specimens submitted to the
      cytogenetics laboratory between January and June of 2011 that were split and
      analyzed in parallel by our traditional algorithm (culture and G-banding, plus an
      interphase FISH aneuploidy panel for culture failures) and the proposed "no
      culture" algorithm (first line QF-PCR, plus array CGH on normal QF-PCRs). Data on
      clinical impact, cost, and turnaround time were collected. RESULTS: Forty
      specimens were included. The algorithms produced results that were fully
      concordant in 22 cases, partially concordant in 9 cases, and discordant in 9
      cases. The no-culture algorithm detected new, clinically-significant
      abnormalities in 8 of 40 cases (20%), corrected the sex chromosome assortment in
      1 case, reduced the analysis failure rate from 10% to 0%, and provided at least
      one of these three important benefits in 12 of 40 cases (30%). The algorithm also
      demonstrated a reduced cost per-specimen and per diagnosis, as well as improved
      turnaround time, with virtually all cases reported per guidelines. CONCLUSION:
      These striking results favor the "no-culture" algorithm, which may have the
      potential to replace standard cytogenetic methods in the clinical laboratory.

PMID- 22612984
TI  - The impact of the various chemical and physical factors on the degradation rate
      of bronopol.
AB  - Bronopol (2-bromo-2-nitropropane-1,3-diol) is used as preservative in cosmetic
      industry. Its main role in commercial products consists in protection of the
      cosmetic composition stability by inhibiting the development of micro-organisms.
      Unfortunately, preservatives can also undergo the degradation processes. The aim
      of examinations was to prove that bronopol decomposes in aqueous solutions and
      storage conditions have a significance influence on its degradation rate. High
      performance liquid chromatography method (methanol/water with hydrochloric acid
      5:95 v/v) with spectrophotometric detection (210 nm) was used for examining the
      decomposition rate of bronopol. The impact of chemical (addition of cosmetics
      components: citric acid and/or sodium dodecylsulfate) and physical (elevated and
      ambient temperature, sunlight or ultraviolet radiation and air access) factors
      has been elaborated. Bronopol decomposes most rapidly (independently on the
      sample surrounding conditions) when it is in solution with sodium dodecylsulfate,
      the inverse dependence is observed in the presence of two compounds - citric acid
      and sodium dodecylsulfate. Additionally, the elevated temperature causes the
      acceleration of decomposition. Bronopol degradation by-products were also
      identified as methanol, formic acid, tris(hydroxymethyl)methane and 2-bromo-2
      nitroethanol.

PMID- 22612985
TI  - Tadalafil 5 mg daily treatment for type 1 diabetic premenopausal women affected
      by sexual genital arousal disorder.
AB  - INTRODUCTION: Type 1 diabetic women may be affected by sexual dysfunction, mainly
      due to peripheral vascular disease. AIM: To determine whether daily tadalafil 5
      mg is effective in type 1 premenopausal women affected by sexual genital arousal
      disorder. METHOD: Thirty-three volunteers were enrolled in a 12-week daily
      tadalafil 5 mg prospective study. MAIN OUTCOME MEASURES: The efficacy of daily
      tadalafil 5 mg on sexual genital arousal (primary end point), and desire, orgasm,
      enjoyment and frequency of sexual activity, and genital pain (secondary end
      points) were assessed (i) subjectively by the Short Personal Experiences
      Questionnaire; and (ii) objectively by translabial color Doppler sonography of
      clitoral blood flow. Moreover, the Short Form-36 questionnaire was used to assess
      Quality of Life (QoL). RESULTS: Thirty-two women completed the study. Women
      reported a QoL improvement at the 12th week follow-up (P<0.05). Tadalafil
      improved the experience of sexual genital arousal, and orgasm, sexual enjoyment,
      satisfaction by frequency of sexual activity, and frequency of sexual thoughts or
      fantasies (P<0.05). Finally, dyspareunia decreased with respect to baseline
      (P<0.001). After tadalafil administration, the mean peak systolic velocity
      increased and the mean diastolic velocity decreased from baseline (P<0.001).
      Moreover, the mean resistance index and the mean pulsatility index were
      significantly higher compared with baseline values (P<0.001). CONCLUSIONS: Daily
      tadalafil 5 mg treatment seems to improve subjective sexual aspects and could be
      used to treat genital arousal disorder of premenopausal women with type 1
      diabetes. The limits of the study were the small sample and the lack of a placebo
      control group.

PMID- 22612986
TI  - Different tracheotomy tube diameters influence diaphragmatic effort and indices
      of weanability in difficult to wean patients.
AB  - OBJECTIVE: To determine the effects of different tracheotomy tube sizes on
      diaphragm effort and weanability indices. METHODS: Ten tracheotomized and
      difficult to wean subjects were randomized to 2 T-piece trials, with different
      tracheotomy tube diameters: inner diameters 8 mm and 6.5 mm. Diaphragm pressure
      time product per min. (PTP(di/min)), lung compliance and resistance (C(L) and
      R(L)), breathing pattern, tension-time index of the diaphragm (TT(di)), and the
      ratio of breathing frequency to tidal volume (f/V(T)) were recorded. In an in
      vitro model, the flow-pressure relationship was measured using the 2 tracheotomy
      tubes and 2 endotracheal tubes of the same diameter. RESULTS: The use of a
      smaller diameter resulted in an increase of PTP(di) (337.63 +/- 194.35 cm H(2)O .
      s/min vs 263.28 +/- 156.23 cm H(2)O . s/min for 6.5 mm and 8 mm, respectively, P
      = .004) and R(L) (16.74 +/- 8.10 cm H(2)O . s/min vs 11.72 +/- 7.88 cm H(2)O .
      s/min, respectively, P = .008). Both weanability indices were also significantly
      higher using the smaller tube: f/V(T) 93.32 +/- 20.91 vs 77.06 +/- 19.26 for 6.5
      mm and 8 mm, respectively, P < .02; TT(di) 0.09 +/- 0.052 vs 0.08 +/- 0.04,
      respectively, P < .02. In vitro measurements confirmed that the resistances were
      higher with the smaller diameter and similar between the tracheotomy tubes and
      the endotracheal tubes of the same diameters. CONCLUSIONS: In tracheotomized
      difficult to wean subjects the decrease of the tracheotomy tube size was
      associated with an increased PTP(di), f/V(T), and TT(di), that were otherwise
      normal, using a higher diameter. The in vitro study showed that the resistances
      increased similarly for tracheotomy tube and endotracheal tube, decreasing the
      diameter and increasing the flows.

PMID- 22612987
TI  - Substance use initiation: the role of simultaneous polysubstance use.
AB  - INTRODUCTION AND AIMS: Simultaneous polysubstance use (SPU) is a common
      phenomenon, yet little is known about its role in substance use initiation.
      DESIGN AND METHODS: In the present study, 226 cannabis users completed structured
      interviews about their substance use history. For each substance ever used,
      participants provided details of their age of first use, their use in the
      preceding 30 days and whether they co-administered any other licit or illicit
      substances the first time they used the substance. RESULTS: For most illicit
      substances [powder cocaine, crack, amphetamine, methamphetamine, 3,4
      methylenedioxymethamphetamine (MDMA; ecstasy), heroin, opium, gamma
      hydroxybutyric acid (GHB), ketamine, psilocybin (magic mushrooms), mescaline,
      phencyclidine (PCP), peyote and inhalants], results showed that a clear majority
      of participants (>=75%) reported SPU during their first-ever use of the
      substance. While SPU was less common on occasions of first use of alcohol,
      tobacco and cannabis, a high proportion of SPU on occasions of first use of
      'harder' drugs could be accounted for by the co-use of alcohol, tobacco and/or
      cannabis. DISCUSSION AND CONCLUSIONS: Such findings raise the possibility that
      specific alcohol, tobacco and/or cannabis use episodes might directly contribute
      to the initiation of new substance use. Understanding the role of SPU on
      occasions of first use might help better identify risk factors for substance use
      progression and improve intervention efforts.

PMID- 22612988
TI  - Metabonomic analysis reveals the CCl4-induced systems alterations for multiple
      rat organs.
AB  - CCl(4)-induced metabonomic changes have been extensively studied for mammalian
      liver, and such changes have not been reported for other organs. To investigate
      the CCl(4) effects on other organs, we analyzed the CCl(4)-induced metabonomic
      changes in rat kidney, lung, and spleen using (1)H NMR-based metabonomics
      approaches with complementary information on serum clinical chemistry and
      histopathology. We found that acute CCl(4) exposure caused significant level
      elevation for creatine and decline for glucose, taurine, trimethylamine, uridine,
      and adenosine in rat kidney. CCl(4)-treatment also induced elevation of amino
      acids (isoleucine, leucine, valine, threonine, alanine, lysine, ornithine,
      methionine, tyrosine, phenylalanine, and histidine), creatine, and betaine in rat
      lung together with depletion of glycogen, glucose, taurine, glycine, and
      hypoxanthine. Furthermore, CCl(4) caused elevation of lactate, alanine, betaine,
      and uracil in rat spleen accompanied with decline for glucose, choline, and
      hypoxanthine. These observations indicated that CCl(4) caused oxidative stresses
      to multiple rat organs and alterations of their functions including renal osmotic
      regulations, accelerated glycolysis, and protein and nucleotide catabolism. These
      findings provide essential information on CCl(4) toxicity to multiple rat organs
      and suggest that systems toxicological views are required for metabonomic studies
      of toxins by taking many other organs into consideration apart from so-called
      targeted ones.

PMID- 22612989
TI  - Operant behavior to obtain palatable food modifies neuronal plasticity in the
      brain reward circuit.
AB  - Palatability enhances food intake by hedonic mechanisms that prevail over caloric
      necessities. Different studies have demonstrated the role of endogenous
      cannabinoids in the mesocorticolimbic system in controlling food hedonic value
      and consumption. We hypothesize that the endogenous cannabinoid system could also
      be involved in the development of food-induced behavioral alterations, such as
      food-seeking and binge-eating, by a mechanism that requires neuroplastic changes
      in the brain reward pathway. For this purpose, we evaluated the role of the CB1
      cannabinoid receptor (CB1-R) in the behavioral and neuroplastic changes induced
      by operant training for standard, highly caloric or highly palatable isocaloric
      food using different genetics, viral and pharmacological approaches.
      Neuroplasticity was evaluated by measuring changes in dendritic spine density in
      neurons previously labeled with the dye DiI. Only operant training to obtain
      highly palatable isocaloric food induced neuroplastic changes in neurons of the
      nucleus accumbens shell and prefrontal cortex that were associated to changes in
      food-seeking behavior. These behavioral and neuroplastic modifications induced by
      highly palatable isocaloric food were dependent on the activity of the CB1-R.
      Neuroplastic changes induced by highly palatable isocaloric food are similar to
      those produced by some drugs of abuse and may be crucial in the alteration of
      food-seeking behavior leading to overweight and obesity.

PMID- 22612990
TI  - Functional analysis of gene expression in risperidone treated cells provide new
      insights in molecular mechanism and new candidate genes for pharmacogenetic
      studies.
AB  - Risperidone is a potent antagonist of both dopamine and serotonin receptors.
      However, little is known about the underlying molecular mechanism by which
      risperidone acts. Although a number of genetic variants have been observed to
      correlate with treatment response there are no definitive predictors of response.
      We performed a genome-wide gene expression analysis (Human Genome U219 Array
      Plate) of a human neuroblastoma cell line (SK-N-SH) exposed to risperidone to
      identify molecular mechanisms involved in the cellular response to risperidone
      and thus identify candidate genes for pharmacogenetic studies. Our results
      revealed that cellular risperidone treatment is associated with a range of gene
      expression changes, which are time (6-48h) and dose related (0.1-10MUM). We found
      that functional clusters of these changes correspond to Gene Ontology categories
      related to neural cell development functions, and synaptic structure and
      functions. We also identified Canonical Pathways related to these functional
      categories: neurogenesis and axon guidance; synaptic vesicle; and
      neurotransmitter signaling (dopamine, serotonin and glutamate). Finally, we
      identified candidate genes for pharmacogenetic studies related to the main
      risperidone secondary effects: motor disorders, cardiovascular disorders and
      metabolic disorders. Our results suggest that risperidone treatment affects the
      neurogenesis and neurotransmission of neuroblastoma cells, which is in agreement
      with the "initiation and adaptation" model to explain the mechanism of action of
      psychotropic drugs.

PMID- 22612991
TI  - Lu AA21004, a novel multimodal antidepressant, produces regionally selective
      increases of multiple neurotransmitters--a rat microdialysis and
      electrophysiology study.
AB  - The monoaminergic network, including serotonin (5-HT), norepinephrine (NE), and
      dopamine (DA) pathways, is highly interconnected and has a well-established role
      in mood disorders. Preclinical research suggests that 5-HT receptor subtypes,
      including 5-HT1A, 5-HT1B, 5-HT3, and 5-HT7 receptors as well as the 5-HT
      transporter (SERT), may have important roles in treating depression. This study
      evaluated the neuropharmacological profile of Lu AA21004, a novel multimodal
      antidepressant combining 5-HT3 and 5-HT7 receptor antagonism, 5-HT1B receptor
      partial agonism, 5-HT1A receptor agonism, and SERT inhibition in recombinant cell
      lines. Extracellular 5-HT, NE and DA levels were evaluated in the ventral
      hippocampus (vHC), medial prefrontal cortex (mPFC) and nucleus accumbens (NAc)
      after acute and subchronic treatment with Lu AA21004 or escitalopram. The acute
      effects of LuAA21004 on NE and DA neuronal firing were also evaluated in the
      locus coeruleus (LC) and ventral tegmental area (VTA), respectively. Acute Lu
      AA21004 dose-dependently increased 5-HT in the vHC, mPFC and NAc. Maximal 5-HT
      levels in the vHC were higher than those in the mPFC. Furthermore, mPFC 5-HT
      levels were increased at low SERT occupancy levels. In the vHC and mPFC, but not
      the NAc, high Lu AA21004 doses increased NE and DA levels. Lu AA21004 slightly
      decreased LC NE neuronal firing and had no effect on VTA DA firing. Results are
      discussed in context of occupancy at 5-HT3, 5-HT1B and 5-HT1A receptors and SERT.
      In conclusion, Lu AA21004, acting via two pharmacological modalities, 5-HT
      receptor modulation and SERT inhibition, results in a brain region-dependent
      increase of multiple neurotransmitter concentrations.

PMID- 22612992
TI  - Proteomic changes in response to potassium starvation in the extremophilic yeast
      Debaryomyces hansenii.
AB  - In this work, we performed for the first time a proteomic approach to the
      processes induced by long-term potassium starvation in the halotolerant yeast
      Debaryomyces hansenii. The proteomic profile under this ionic stress conditions
      shows that important changes in gene expression take place as an adaptive
      response. We found a significant protein expression repression as well as
      metabolic changes such as the inhibition of the upper part of the glycolysis, the
      amino acid synthesis, and the Krebs cycle. On the other hand, genes related to
      stress responses, protein degradation, and sterols synthesis were upregulated in
      response to potassium deprivation. The findings in this study provide important
      information about how this particular yeast copes with ionic stress at molecular
      levels, which might further enrich the global understanding of salt tolerance
      processes in eukaryal systems and moreover highlighting the importance of the
      'omics' approaches as a complement to the classical physiological studies.

PMID- 22612993
TI  - Cost effectiveness of rituximab for non-Hodgkin's lymphoma: a systematic review.
AB  - BACKGROUND: The monoclonal antibody rituximab has shown clinical effectiveness in
      combination with chemotherapy for the treatment of non-Hodgkin's lymphoma (NHL)
      in several randomized controlled studies. Rituximab maintenance therapy is
      associated with significant improvement in progression-free and overall survival
      in patients with NHL. However, treatment with rituximab causes considerable costs
      for healthcare systems. OBJECTIVE: This article provides an overview of economic
      evaluations of rituximab and appraises their methodological quality. METHODS: A
      systematic literature search of cost-effectiveness studies on rituximab was
      carried out in nine electronic databases: MEDLINE, EMBASE, Cochrane Database of
      Systematic Reviews (CDSR), the German Agency of Health Technology Assessment
      (DAHTA) database, German Institute for Quality Improvement (DIQ)-Literatur, DIQ
      Projekte, Database of Abstracts of Reviews of Effects (DARE), Health Technology
      Assessments (HTA) database and Sozialmedizin (SOMED) [languages: English, German,
      Dutch, French, Spanish and Italian; publication period: 1998 to 2010]. Based on
      pre-specified inclusion criteria, cost-effectiveness studies were identified that
      compared standard chemotherapy with standard chemotherapy plus rituximab in
      patients with a subtype of NHL. The methodological quality of the studies was
      assessed using a quality checklist. RESULTS: Fourteen economic evaluations from
      seven different countries were included in the review. All economic evaluations
      reported incremental cost-effectiveness ratios (ICERs) for the add-on therapy
      with rituximab that were below the country-specific thresholds. The studies
      differed significantly in their characteristics and methodological rigour. Most
      studies lacked transparency regarding identification and justification of data.
      In several studies, the rationale for the model structure was not described
      appropriately. CONCLUSION: Adding rituximab to standard chemotherapy is
      considered a cost-effective treatment option for NHL. However, the results of the
      analyses should be interpreted with caution due to methodological limitations.

PMID- 22612994
TI  - Continuous chelation irrigation improves the adhesion of epoxy resin-based root
      canal sealer to root dentine.
AB  - AIM: To test the impact of continuous chelation by NaOCl+ etidronic acid (HEBP)
      during instrumentation, and a final rinse of EDTA or NaOCl + HEBP on the dentine
      bond strength of an epoxy resin sealer (AH Plus). METHODOLOGY: Single-rooted
      teeth (n = 100) were divided into five groups (n = 20) based on the irrigation
      protocol and their root canals instrumented using a rotary Ni-Ti system: 2.5%
      NaOCl during instrumentation followed by bi-distilled water (G1) or 17% EDTA (G2)
      as final rinse; 1 : 1 mixture of 5% NaOCl and 18% HEBP during instrumentation,
      and the same mixture (G3), 17% EDTA (G4) or bi-distilled water (G5) as final
      rinse. Canals were filled with AH Plus. Roots were sectioned, and push-out tests
      were performed in coronal, middle and apical root thirds. Results were analysed
      using analysis of variance (anova) and Bonferroni test for multiple comparisons.
      The alpha-type error was set at 0.05 for all the analyses. RESULTS: Push-out bond
      strength was highest in coronal and lowest in apical root thirds (P < 0.05).
      Groups that used NaOCl + HEBP irrigation during instrumentation had significantly
      higher bond strengths than groups following the NaOCl-EDTA irrigation in all root
      thirds (P < 0.05). The use of a strong chelator as final flush further increased
      bond strengths (G4, P < 0.05). CONCLUSION: The continuous chelation irrigation
      protocol optimizes the bond strength of an epoxy resin sealer to dentine.

PMID- 22612995
TI  - Male infertility after endoscopic Totally Extraperitoneal (Tep) hernia repair
      (Main): rationale and design of a prospective observational cohort study.
AB  - BACKGROUND: To describe the rationale and design of an observational cohort study
      analyzing the effects of endoscopic Totally Extraperitoneal (TEP) hernia repair
      on male fertility (MAIN study). METHODS AND DESIGN: The MAIN study is an
      observational cohort study designed to assess fertility after endoscopic TEP
      hernia repair. The setting is a high-volume single center hospital, specialized
      in TEP hernia repair. Male patients of 18-60 years of age, with primary,
      reducible, bilateral inguinal hernias and no contraindications for endoscopic TEP
      repair are eligible for inclusion in this study. Patients with an ASA
      classification>=III and patients with recurrent and/or scrotal hernias and/or a
      medical history of pelvic surgery and/or radiotherapy, known fertility problems,
      diabetes and/or other diseases associated with a risk of fertility problems, will
      be excluded. The primary outcome is the testicular perfusion before and 6 months
      after TEP hernia repair (assessed by means of a scrotal ultrasonography).
      Secondary endpoints are the testicular volume (Ultrasound), semen quality and
      quantity and the endocrinological status, based on serum levels of the sexual
      hormones follicle-stimulating hormone (FSH), luteinizing hormone (LSH),
      testosterone and inhibin B before and 6 months after TEP hernia repair.
      DISCUSSION: The use of polypropylene mesh is associated with a strong foreign
      body reaction which could play a role in chronic groin pain development. Since
      the mesh in (endoscopic) inguinal hernia repair is placed in close contact to the
      vas deferens and spermatic vessels, the mesh-induced inflammatory reaction could
      lead to a dysfunction of these structures. Relevant large and prospective
      clinical studies on the problem are limited. This study will provide a complete
      assessment of fertility in male patients who undergo simultaneous bilateral
      endoscopic TEP hernia repair, by analyzing testicular perfusion and volume, semen
      quantity and quality and endocrinological status before and 6 months after TEP
      repair. TRIAL REGISTRATION: The MAIN study is registered in the Dutch Trial
      Register (NTR2208).

PMID- 22612996
TI  - Prospective assessment of renal histopathological lesions in patients with end
      stage liver disease: effects on long-term renal function after liver
      transplantation.
AB  - BACKGROUND & AIMS: The incidence of organic renal lesions in patients with end
      stage liver disease is unknown. The goal of this study was to make a prospective
      evaluation of renal histological lesions in a group of unselected patients
      awaiting liver transplantation. METHODS: Sixty cirrhotic patients underwent a
      renal biopsy via the transjugular route. The potential effect of renal lesions on
      renal function was evaluated five years after transplantation. RESULTS: The yield
      of biopsies enabling satisfactory analysis was 77%, and no major complications
      occurred. Proteinuria>0.5 g/day was observed in only 8.7% of these patients,
      microscopic haematuria in 4.3%, creatinine levels>133 mmol/L (1.5mg/dl) in 10.9%,
      and Modification of the Diet in Renal Disease (MDRD) clearance<60 ml/min in
      13.0%. Twenty-five patients (55.3%) had a morphological diagnosis of renal
      disease, 15 displayed IgA nephropathy and immunofluorescence testing showed that
      12 had specific diabetic linear staining for IgG and albumin, of whom seven had
      associated histological lesions of diabetic nephropathy. Five years after liver
      transplantation, renal function had significantly deteriorated more in patients
      with initial diabetic lesions than in those with normal histology or IgA
      nephropathy alone. CONCLUSIONS: In patients with end-stage liver disease, IgA
      nephropathy and diabetic lesions were frequently found despite the absence of
      renal impairment and/or urinalysis anomalies. Our results strongly suggest that
      severe renal failure develops preferentially in liver transplant recipients with
      diabetes or carbohydrate intolerance, and that pre-existing arterial lesions may
      favour the nephrotoxicity of calcineurin inhibitors. Diabetes prior to
      transplantation needs to be strictly managed and requires a renal sparing
      immunosuppressive regimen after transplantation.

PMID- 22612997
TI  - Unexpectedly high proportion of drug users and men having sex with men who
      develop chronic hepatitis B infection.
AB  - BACKGROUND & AIMS: In low endemic countries, most hepatitis B virus (HBV)
      infections are found in adult behavioural risk groups, such as drug users (DU)
      and men having sex with men (MSM). These risk groups are frequently exposed to
      HBV, which might induce a different rate of viral clearance compared with the
      general adult population, in whom the chronicity rate is estimated to be 5-10%.
      Our aim was to obtain insights into the proportion of MSM and DU developing
      chronic infection after a primary HBV infection, and the underlying risk factors.
      METHODS: From 1984 to 2002, sera of 1862 MSM and 1268 DU of the Amsterdam Cohort
      Studies were retrospectively tested for anti-HBc, HBsAg, and HBV DNA. As of 2003,
      all of the cohort participants were vaccinated, making further testing redundant.
      RESULTS: Hundred and forty seven participants seroconverted for anti-HBc during
      follow-up. The median age at the moment of the acute infection was 31 years. The
      proportion of those becoming chronically infected was 23% and 28% for MSM and DU,
      respectively. In both cohorts, being younger was a risk factor for developing
      chronic infection (OR: 0.9; 95% CI: 0.82-0.99). HIV/HCV co-infection was
      associated with developing chronic HBV infection in the DU cohort (OR: 32.1, 95%
      CI: 3.1-334.5). CONCLUSIONS: Compared with the general population, MSM and DU had
      an unanticipated high rate of developing chronic HBV infections. HIV/HCV co
      infection proved to be an important risk factor for developing chronic HBV
      infections in DU. The reason for the high rate of MSM becoming chronically
      infected remains unclear.

PMID- 22612998
TI  - Validation of liver fibrosis biomarker (FibroTest) for assessing liver fibrosis
      progression: proof of concept and first application in a large population.
AB  - BACKGROUND & AIMS: Time-dependent statistics have been used to assess liver
      fibrosis progression (LFP) in liver diseases from birth to first biopsy, in a
      limited number of patients. Non-invasive biomarkers such as FibroTest (FT) should
      allow the estimation of LFP on larger populations. We aimed at validating this
      concept by comparing LFP using FT vs. biopsy (P1) and then at applying the non
      invasive method to a large population (P2). METHODS: In P1, LFP was assessed
      using biopsy and FT in 2472 untreated patients: 770 with chronic hepatitis C, 723
      with hepatitis B, 761 with non-alcoholic fatty liver disease (NAFLD), and 218
      with alcoholic fatty liver disease (ALD). In P2, 342,346 interpretable FT
      prospectively measured were used. LFP was estimated using transition rates
      (cumulative hazard rate) to cirrhosis (F4) or to minimal fibrosis (>F0). RESULTS:
      In P1, there was a significant concordance between FT and biopsy estimates of
      hazards with intraclass correlation (ICC)=0.961 (95% CI 0.948-0.970) and 0.899
      (95% CI 0.135-0.969) for F4 and >F0, respectively. This concordance persisted
      according to the disease and the gender. The more rapid LFP to F4 (biopsy/FT) was
      observed for men with ALD (1.44/1.62), and the slower for women with NAFLD
      (0.09/0.02). In P2, the LFP started to increase for men at the age of 30 years.
      The cumulative fibrosis progression rate to minimal fibrosis in women crossed the
      "man curve" around the age of 80 years. The following factors were associated
      with LFP to F4 (all p<0.0001): male gender (Relative Risk=3.29), HIV co-infection
      (2.33), and residency in Middle East (2.67) or Eastern Europe (2.15).
      CONCLUSIONS: Validated biomarkers such as FibroTest should allow powerful
      analysis of fibrosis progression in chronic liver diseases and better
      identification of risk factors.

PMID- 22612999
TI  - OV6+ tumor-initiating cells contribute to tumor progression and invasion in human
      hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Accumulating evidence suggests the involvement of tumor
      initiating cells (T-ICs) in cancer genesis, but whether liver T-ICs contribute to
      HCC invasion and metastasis remains unclear. METHODS: OV6(+) T-ICs were isolated
      from SMMC7721 and HuH7 cell lines by magnetic sorting. Characteristics of T-ICs
      were assessed by in vitro and mouse xenograft assays. Expression of OV6 was
      determined by immunostaining in specimens from 218 HCC patients, and Kaplan-Meier
      survival analysis was used to determine the correlation of OV6 expression with
      prognosis. RESULTS: OV6(+) T-ICs isolated from HCC cell lines not only possess a
      higher capacity to form tumor spheroids in vitro, but also had a greater
      potential to form tumors when implanted in non-obese diabetic/severe combined
      immunodeficient mice, suggesting their elevated self-renewal capacity and
      tumorigenicity. Moreover, OV6(+) T-ICs exhibited more invasive and metastatic
      potentials both in vitro and in vivo. Patients with more OV6(+) tumor cells were
      associated with aggressive clinicopathologic features and poor prognosis. CXCR4
      is expressed at higher levels in OV6(+) cells. Recombinant stromal cell-derived
      factor-1 (SDF-1) treatment expanded the OV6(+) HCC T-ICs population, by
      sustaining the stem cell property of OV6(+) cells. The SDF-1 effect was blocked
      by a specific CXCR4 inhibitor, AMD3100, or transfection of siRNA targeting CXCR4.
      CONCLUSIONS: OV6(+) HCC cells may represent a subpopulation of T-ICs with
      augmented invasion and metastasis potential, which contribute to progression and
      metastasis of HCC. The SDF-1/CXCR4 axis also provides therapeutic targets for
      elimination of liver T-ICs.

PMID- 22613000
TI  - Insulin resistance undermines the advantages of IL28B polymorphism in the
      pegylated interferon alpha-2b and ribavirin treatment of chronic hepatitis C
      patients with genotype 1.
AB  - BACKGROUND & AIMS: Recent studies have suggested that insulin resistance exerts a
      strong influence on chronic hepatitis C virus (HCV) infection. We analyzed
      pretreatment factors useful for predicting sustained virological response (SVR),
      especially interleukin (IL) 28B polymorphism and Homeostasis Model Assessment of
      Insulin Resistance (HOMA-IR). METHODS: This cohort study consisted of 328 chronic
      hepatitis C patients with HCV genotype 1 who were treated for 48 weeks with
      pegylated interferon (PegIFN) alpha-2b and ribavirin (RBV). Genotyping of the
      polymorphisms in the IL28B gene region (rs8099917) on chromosome 19 was performed
      on DNA collected from each patient. RESULTS: No significant difference in IL28B
      genotype distribution was found according to HOMA-IR. Multivariate analysis
      identified the IL28B TT genotype (OR=5.97, 95% CI 2.15-16.55, p=0.0006) and the
      baseline HOMA-IR (OR=0.65, 95% CI 0.48-0.87, p=0.0044) as significant,
      independent pretreatment predictors of SVR. Receiver operating characteristic
      analyses to determine the optimal threshold values of HOMA-IR for predicting SVR
      showed that the areas under the curve (AUC) were high for both IL28B TT
      (AUC=0.774, HOMA-IR cut-off value: 2.45) and IL28B TG/GG genotypes (AUC=0.772,
      HOMA-IR cut-off value: 1.55). CONCLUSIONS: For HCV genotype 1, both IL28B and
      baseline HOMA-IR are independent pretreatment predictors of SVR in patients
      treated with PegIFNalpha-2b and RBV. Insulin resistance undermines the advantages
      of IL28B polymorphism to obtain SVR.

PMID- 22613001
TI  - Treatment of recurrent HCV infection following liver transplantation: results of
      a multicenter, randomized, versus placebo, trial of ribavirin alone as
      maintenance therapy after one year of PegIFNalpha-2a plus ribavirin.
AB  - BACKGROUND & AIMS: We aimed at determining the effect of maintenance therapy with
      ribavirin alone, after a year of combined peginterferon-alfa 2a (PegIFNalpha-2a)
      and ribavirin therapy, on viral response and liver histology after liver
      transplantation (LT). METHODS: Hundred and one patients with recurrent HCV and a
      minimum of stage 1 fibrosis (METAVIR scoring), 1-5years after LT, were enrolled.
      PegIFNalpha-2a and ribavirin were initiated at 90 MUg/wk and 600 mg/d,
      respectively, then increased or adjusted as a function of tolerance. At 12
      months, combination therapy was discontinued and patients were randomized to
      ribavirin or placebo for a further 12 months. Growth factor use was permitted.
      RESULTS: At 18 months, a sustained virological response (SVR) was obtained in
      47.9% of patients in Per Protocol (PP) analysis, and was higher in patients with
      genotype 2 or 3 than in patients with genotype 1 or 4, in patients with genotypes
      1+4 receiving ciclosporine than in those receiving tacrolimus, in patients with
      worse renal function, in those having received EPO, in patients with lower
      weight, and in those with lower viral load at 3 months. Using logistic
      regression, only the early viral response, recipient weight and renal function
      were independently associated with better SVR. SVR, viral load, activity, and
      fibrosis scores were similar, at M18 and M30, in patients randomized to
      ribavirin, or to placebo. CONCLUSIONS: A PP SVR was achieved in 47.9% of patients
      with established recurrent hepatitis C after LT. Maintenance therapy with
      ribavirin alone does not improve the virological response or the histological
      parameters.

PMID- 22613002
TI  - Cholestasis-induced pruritus treated with ultraviolet B phototherapy: an
      observational case series study.
AB  - BACKGROUND & AIMS: Pruritus is a disabling complication of cholestatic liver
      disorders. Its management remains challenging. Ultraviolet B (UVB) phototherapy
      has been successfully used to treat pruritus in other indications. METHODS: This
      is an observational case series. The study population consists of 13 patients (10
      females, mean age 52 years) with pruritus due to different cholestatic liver
      disorders: PBC (n=4), PSC (n=2), drug-induced (n=3) and persistent cholestasis
      after liver transplantation (LT) (n=4). Serum alkaline phosphatase levels were:
      686 +/- 363 MU/L and serum bile acids levels: 147 +/- 15 MUmol/L. In all
      patients, conventional medical treatment had failed to control pruritus.
      Perception of pruritus was recorded by the visual analogue scale (VAS). RESULTS:
      The mean follow-up was 3 years. Ten patients (77%) had more than 60% reduction in
      perceived pruritus of which 4 had more than an 80% reduction. Median [25-75%
      percentiles] VAS score before and after treatment decreased from 8.0 [8.0-10] to
      2.0 [1.5-2.1] (p<0.001). The mean number of irradiations required to obtain this
      effect was 26 +/- 17 (average duration of phototherapy: 8 weeks). No significant
      changes in cholestatic serum markers were observed. Four patients (30%) needed an
      additional phototherapy course because of recurrent pruritus and in all of them
      again a marked improvement of pruritus was observed. The therapy was well
      tolerated, except in two patients who developed, during retreatment, pronounced
      erythema in one case and paresthesia in the other case. CONCLUSIONS: UVB
      phototherapy appears to be a promising and well tolerated treatment also for
      cholestasis-associated pruritus.

PMID- 22613003
TI  - Hepatitis C virus (HCV) protein expression enhances hepatic fibrosis in HCV
      transgenic mice exposed to a fibrogenic agent.
AB  - BACKGROUND & AIMS: During chronic HCV infection, activation of fibrogenesis
      appears to be principally related to local inflammation. However, the direct role
      of hepatic HCV protein expression in fibrogenesis remains unknown. METHODS: We
      used transgenic mice expressing the full length HCV open reading frame exposed to
      a 'second hit' of the fibrogenic agent carbon tetrachloride (CCl(4)). Both acute
      and chronic liver injuries were induced in these mice by CCl(4) injections. Liver
      injury, expression of matrix re-modeling genes, reactive oxygen species (ROS),
      inflammation, hepatocyte proliferation, ductular reaction and hepatic progenitor
      cells (HPC) expansion were examined. RESULTS: After CCl(4) treatment, HCV
      transgenic mice exhibited enhanced liver fibrosis, significant changes in matrix
      re-modeling genes and increased ROS production compared to wild type littermates
      despite no differences in the degree of local inflammation. This increase was
      accompanied by a decrease in hepatocyte proliferation, which appeared to be due
      to delayed hepatocyte entry into the S phase. A prominent ductular reaction and
      hepatic progenitor cell compartment expansion were observed in transgenic
      animals. These observations closely mirror those previously made in HCV-infected
      individuals. CONCLUSIONS: Together, these results demonstrate that expression of
      the HCV proteins in hepatocytes contributes to the development of hepatic
      fibrosis in the presence of other fibrogenic agents. In the presence of CCl(4),
      HCV transgenic mice display an intra-hepatic re-organization of several key
      cellular actors in the fibrogenic process.

PMID- 22613004
TI  - Upregulated FoxM1 expression induced by hepatitis B virus X protein promotes
      tumor metastasis and indicates poor prognosis in hepatitis B virus-related
      hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Forkhead box M1 (FoxM1) is a master regulator of tumor
      metastasis that plays an important role in the development of hepatocellular
      carcinoma (HCC). However, whether or not FoxM1 contributes to the progression of
      HBV-associated HCC (HBV-HCC) remains unknown. Therefore, we aimed at
      investigating the clinicopathologic significance of FoxM1 in HBV-HCC and the
      potential role of FoxM1 in hepatitis B virus X (HBx)-mediated invasiveness and
      metastasis. METHODS: The expression of FoxM1 and its functional targets matrix
      metalloproteinase-7 (MMP-7), RhoC, and Rho-kinase 1 (ROCK1) in human HBV-HCC
      tissues was detected by immunohistochemistry. Luciferase reporter, chromatin
      immunoprecipitation, and electrophoretic mobility shift assays were used to
      measure the transcriptional regulation of FoxM1 promoter by HBx. The effect of
      FoxM1 on HBx-mediated invasiveness and metastasis was analyzed by transwell
      assays and an orthotopic metastatic model. RESULTS: FoxM1 overexpression
      correlated with multiple malignant characteristics and indicated poor prognosis
      of HBV-HCC patients. FoxM1 expression was an independent factor affecting the
      recurrence and survival of patients with HBV-HCC after surgical resection. FoxM1
      promoted hepatoma cell invasion and metastasis by promoting MMP-7, RhoC, and
      ROCK1 expression, while FoxM1 overexpression was associated with elevated
      expressions of these proteins in HBV-HCC tissues. HBx upregulated FoxM1
      expression through the ERK/CREB pathway, and FoxM1 inhibition significantly
      decreased HBx-enhanced hepatoma cell invasion in vitro and lung metastasis in
      vivo. CONCLUSIONS: We report a new molecular mechanism for HBV-associated
      hepatocarcinogenesis that involves the activation of FoxM1 expression by HBx
      through the ERK/CREB pathway, thereby leading to invasion and metastasis of
      hepatoma cells.

PMID- 22613005
TI  - MicroRNA-214 downregulation contributes to tumor angiogenesis by inducing
      secretion of the hepatoma-derived growth factor in human hepatoma.
AB  - BACKGROUND & AIMS: Unusual hypervascularity is a hallmark of human hepatocellular
      carcinoma (HCC). Although microRNA-214 (miR-214) is upregulated in other human
      cancers, it is downregulated in HCC. We elucidated the biological and clinical
      significance of miR-214 downregulation in HCC. METHODS: MicroRNAs deregulated in
      HCC were identified using array-based microRNA profiling. A luciferase reporter
      assay confirmed target association between miR-214 and the hepatoma-derived
      growth factor (HDGF). Tube formation and in vivo angiogenesis assays validated
      the roles of miR-214/HDGF in angiogenesis. RESULTS: miR-214 downregulation was
      associated with higher tumor recurrence and worse clinical outcomes. Ectopic
      expression of miR-214 suppressed xenograft tumor growth and microvascularity of
      the tumors and their surrounding tissues. The genes downregulated by ectopic
      expression of miR-214 were involved in the regulation of apoptosis, cell cycle,
      and angiogenesis. Integrated analysis disclosed HDGF as a downstream target of
      miR-214. Conditioned medium of HCC cells contained bioactivity to stimulate tube
      formation of human umbilical vein endothelial cells, which was abolished by
      pretreatment of the conditioned media with HDGF antibodies, suppression of HDGF
      expression or ectopic expression of miR-214 in the donor HCC cells. The
      angiogenic activity of the conditioned media, lost by ectopic expression of miR
      214 in the donor cells, was restored by supplementation with recombinant HDGF. In
      vivo tumor angiogenesis assays showed significant suppression of tumor
      vascularity by ectopic expression of miR-214. CONCLUSIONS: A novel role of
      microRNA in tumorigenesis is identified. Downregulation of miR-214 contributes to
      the unusual hypervascularity of HCC via activation of the HDGF paracrine pathway
      for tumor angiogenesis.

PMID- 22613006
TI  - Liver regeneration.

PMID- 22613007
TI  - Genome-wide association studies of age at menarche and age at natural menopause.
AB  - Genome-wide association studies (GWAS) have been successful in uncovering genetic
      determinants of age at menarche and age at natural menopause. To date, more than
      30 novel genetic loci have been identified in GWAS for age at menarche and 17 for
      age at natural menopause. These findings have stimulated a plethora of follow-up
      studies particularly with respect to the functional characterization of these
      novel loci and how these results can be translated into risk prediction. However,
      the genetic loci identified so far account for only a small fraction of the
      overall heritability. This review provides an overview of the current state of
      our knowledge of the genetic basis of menarche and menopause timing. It
      emphasizes recent GWAS results and outlines strategies for discovering the
      missing heritability and strategies to further our understanding of the
      underlying molecular mechanisms of the observed genetic associations. 

PMID- 22613009
TI  - Familiarity with and attitudes towards epilepsy among teachers at Czech
      elementary schools--the effect of personal experience and subspecialization.
AB  - This study was intended to study the effect of personal experience and
      subspecialization on the knowledge of epilepsy of teachers at Czech elementary
      schools, and on their attitudes towards children with epilepsy and on epilepsy
      itself in general. 193 teachers from 10 different elementary schools in Pilsen,
      Czech Republic, were involved in the study. We found that teachers with personal
      experience of epilepsy had greater knowledge of the illness. There were
      significant differences (P<0.05) between the attitudes of teachers with and
      without personal experience, mostly in terms of their views on the self
      realization and the integration of children with epilepsy into the school
      collective. In contrast, no differences were found in their views of the
      intellectual capabilities of children with epilepsy or the overall quality of
      life of children with epilepsy. Furthermore, we found that subspecialization,
      aside from a few exceptions given by the specific position of first grade
      teachers, did not have major effect on teachers' knowledge of epilepsy and their
      attitudes towards children with epilepsy. The results suggest that it would be
      appropriate to focus educational interventions about epilepsy for teachers on
      those individuals who do not have any experience of epilepsy.

PMID- 22613008
TI  - Importance of NKG2D-NKG2D ligands interaction for cytolytic activity of natural
      killer cell.
AB  - In this study, we investigate the relationship between natural killer (NK) cell
      susceptibility and the surface markers of cancer cells. Through phenotypic
      analysis, we found evidence that more susceptible cancer cell lines (K562 and
      Jurkat) express more NKG2D ligands. Major histocompatibility complex (MHC) class
      I chain-related A/B (MIC-A/B) and UL16 binding protein (ULBP) 1-5 molecules are
      typical ligands of NKG2D. The high killing activity of NK cells against K562 was
      abolished through the addition of a NKG2D blocking antibody. Upon in vitro
      stimulation with quercetin, low susceptible cancer cells increased NKG2D ligand
      expression, leading to enhancement of NK cell cytolytic activity. These results
      suggested that the anti-cancer activity of NK cells is not dependent on the
      origin and growth style of the target cells, but is dependent on the surface
      markers of the target cells.

PMID- 22613010
TI  - Anxiety symptoms in patients with frontal lobe epilepsy versus generalized
      epilepsy.
AB  - PURPOSE: The aim of this study was to compare the frequency of anxiety symptoms
      between patients with frontal lobe epilepsy (FLE) and generalized epilepsy (GE).
      METHODS: Forty and 78 patients with FLE and GE respectively were enrolled in the
      study. Anxiety symptoms were measured with the Hamilton anxiety rating scale
      (HARS) and the anxiety subscale of the hospital anxiety and depression scale
      (HADSA). RESULTS: Compared to the GE group, the FLE group had significantly
      higher HARS (10.9+/-8.7 vs. 7.9+/-6.8, p=0.039) scores. Significant correlations
      were also found between anxiety symptoms and epilepsy-related variables,
      particularly with the seizure frequency and the number of currently taken anti
      epileptic drugs. CONCLUSION: Anxiety symptoms are more common in patients with
      FLE in comparison to those with GE. Further studies are warranted to clarify the
      relationship between anxiety symptoms and FLE.

PMID- 22613011
TI  - Symptom experience and regaining normality in the first year following a
      diagnosis of head and neck cancer: a qualitative longitudinal study.
AB  - INTRODUCTION: Symptom experiences and their interference with life are not well
      researched in head and neck cancer patients. The aim of the study was to explore
      and understand the experience of receiving treatment for head and neck cancer
      with particular focus on symptom experiences over a one year period from
      diagnosis. METHODS: A qualitative study design was used with a heterogeneous
      sample of 16 patients with head and neck cancer. Interviews, conducted at four
      time points over 12 months, provided a total of 50 interview datasets. RESULTS:
      Key themes derived include nutritional concerns, tiredness, and experiences
      related to the radiotherapy mask and regaining normality. These data highlight
      issues of importance in the first year of living with head and neck cancer:
      impact of nutritional changes on the lives of patients, including weight loss,
      dysphagia, xerostomia and taste changes; debilitation from ongoing fatigue;
      unpreparedness for and distress from the radiotherapy mask; and attempts to
      maintain a normal life amidst the interference of symptoms. CONCLUSION: Multitude
      of symptoms impact the patients' life, particularly nutritional symptoms and
      fatigue, and interfere with the patients' survivorship and quality of life. The
      changing nature of symptoms over the first year from diagnosis in head and neck
      cancer patients and the identified issues in the attempt to normalize their lives
      need to be incorporated more fully into the supportive care of head and neck
      cancer patients in order to improve their experience and enhance their
      survivorship.

PMID- 22613012
TI  - Comparative clinical evaluation of the IsoAmp((r)) HSV Assay with ELVIS((r)) HSV
      culture/ID/typing test system for the detection of herpes simplex virus in
      genital and oral lesions.
AB  - BACKGROUND: The novel IsoAmp((r)) HSV Assay employs isothermal helicase-dependent
      nucleic acid amplification and a user-friendly disposable test device to achieve
      rapid (<1.5h), on-demand qualitative detection of herpes simplex virus (HSV)
      types 1 and 2 in oral and genital lesions. OBJECTIVES: To compare performance of
      the IsoAmp((r)) HSV Assay with the ELVIS((r)) HSV ID/typing (shell-vial culture
      and DFA) test system for clinical specimens collected from oral and genital
      lesions in symptomatic patients. STUDY DESIGN: A total of 994 specimens from male
      and female genital and oral lesions were obtained and evaluated at five study
      sites in the United States. Results from the IsoAmp((r)) HSV Assay were compared
      to those from the ELVIS((r)) system. Separate reproducibility studies were
      performed at 3 sites using a blinded and randomized study panel. Discrepant
      specimens were resolved by bidirectional sequencing analysis. RESULTS: After
      discrepant analysis, overall agreement of IsoAmp((r)) with ELVIS((r)) was 98.8%
      with 37.0% overall prevalence (all study sites). Reproducibility rates were well
      within expectations. CONCLUSION: The IsoAmp((r)) HSV Assay showed excellent
      performance for clinical use for detection of HSV in genital and oral specimens.
      In contrast to ELVIS((r)), IsoAmp((r)) HSV offers excellent sensitivity plus
      rapid on-demand testing and simpler specimen preparation.

PMID- 22613013
TI  - Parameters of semantic multisensory integration depend on timing and modality
      order among people on the autism spectrum: evidence from event-related
      potentials.
AB  - Individuals with autism spectrum disorders (ASD) report difficulty integrating
      simultaneously presented visual and auditory stimuli (Iarocci & McDonald, 2006),
      albeit showing enhanced perceptual processing of unisensory stimuli, as well as
      an enhanced role of perception in higher-order cognitive tasks (Enhanced
      Perceptual Functioning (EPF) model; Mottron, Dawson, Soulieres, Hubert, & Burack,
      2006). Individuals with an ASD also integrate auditory-visual inputs over longer
      periods of time than matched typically developing (TD) peers (Kwakye, Foss-Feig,
      Cascio, Stone & Wallace, 2011). To tease apart the dichotomy of both extended
      multisensory processing and enhanced perceptual processing, we used behavioral
      and electrophysiological measurements of audio-visual integration among persons
      with ASD. 13 TD and 14 autistics matched on IQ completed a forced choice
      multisensory semantic congruence task requiring speeded responses regarding the
      congruence or incongruence of animal sounds and pictures. Stimuli were presented
      simultaneously or sequentially at various stimulus onset asynchronies in both
      auditory first and visual first presentations. No group differences were noted in
      reaction time (RT) or accuracy. The latency at which congruent and incongruent
      waveforms diverged was the component of interest. In simultaneous presentations,
      congruent and incongruent waveforms diverged earlier (circa 150 ms) among persons
      with ASD than among TD individuals (around 350 ms). In sequential presentations,
      asymmetries in the timing of neuronal processing were noted in ASD which depended
      on stimulus order, but these were consistent with the nature of specific
      perceptual strengths in this group. These findings extend the Enhanced Perceptual
      Functioning Model to the multisensory domain, and provide a more nuanced context
      for interpreting ERP findings of impaired semantic processing in ASD.

PMID- 22613014
TI  - Attenuation of visceral nociception by alpha-bisabolol in mice: investigation of
      mechanisms.
AB  - BACKGROUND: We previously described the visceral antinociceptive property of
      alpha-bisabolol (BISA) in mouse models of visceral nociception induced by
      cyclophosphamide and mustard oil (MO). This study examined the effect of BISA in
      mouse models of visceral nociception induced by acetic acid, capsaicin, formalin,
      and the contribution of the nitric oxide system, alpha2, KATP, 5-HT3 and TRPV1
      receptors to the effect of BISA on MO-evoked nociceptive behaviors. Mice were
      pretreated orally with BISA (50, 100 and 200 mg/kg) or vehicle, and the pain
      related behavioral responses to intraperitoneal administration of acetic acid or
      intracolonic injection of MO were analyzed. RESULTS: BISA significantly
      suppressed the nociceptive behaviors in a dose-unrelated manner. The
      antinociceptive effect of BISA (50 mg/kg) was show to be glibenclamide resistant,
      but it was not blocked by pretreatment with the other antagonists tested. In the
      open-field test that detects sedative or motor abnormality, mice received 50
      mg/kg BISA did not show any per se influence in ambulation frequency.
      CONCLUSIONS: However, their precise antinociceptive mechanisms of action have not
      been determined.

PMID- 22613015
TI  - Efficacy of two educational interventions about inhalation techniques in patients
      with chronic obstructive pulmonary disease (COPD). TECEPOC: study protocol for a
      partially randomized controlled trial (preference trial).
AB  - BACKGROUND: Drugs for inhalation are the cornerstone of therapy in obstructive
      lung disease. We have observed that up to 75 % of patients do not perform a
      correct inhalation technique. The inability of patients to correctly use their
      inhaler device may be a direct consequence of insufficient or poor inhaler
      technique instruction. The objective of this study is to test the efficacy of two
      educational interventions to improve the inhalation techniques in patients with
      Chronic Obstructive Pulmonary Disease (COPD). METHODS: This study uses both a
      multicenter patients' preference trial and a comprehensive cohort design with 495
      COPD-diagnosed patients selected by a non-probabilistic method of sampling from
      seven Primary Care Centers. The participants will be divided into two groups and
      five arms. The two groups are: 1) the patients' preference group with two arms
      and 2) the randomized group with three arms. In the preference group, the two
      arms correspond to the two educational interventions (Intervention A and
      Intervention B) designed for this study. In the randomized group the three arms
      comprise: intervention A, intervention B and a control arm. Intervention A is
      written information (a leaflet describing the correct inhalation techniques).
      Intervention B is written information about inhalation techniques plus training
      by an instructor. Every patient in each group will be visited six times during
      the year of the study at health care center. DISCUSSION: Our hypothesis is that
      the application of two educational interventions in patients with COPD who are
      treated with inhaled therapy will increase the number of patients who perform a
      correct inhalation technique by at least 25 %. We will evaluate the effectiveness
      of these interventions on patient inhalation technique improvement, considering
      that it will be adequate and feasible within the context of clinical practice.
      TRIAL REGISTRATION: Current Controlled Trials ISRTCTN15106246.

PMID- 22613016
TI  - Computed tomography findings in 32 joints affected with severe elbow incongruity
      and fragmented medial coronoid process.
AB  - OBJECTIVE: To describe the computed tomography (CT) findings in dogs with severe
      elbow incongruity combined with a fragmented medial coronoid process (FCP) and
      compare these with normal joints and congruent joints affected by FCP. STUDY
      DESIGN: Clinical study. ANIMALS: Client-owned dogs with elbow lameness (n = 40)
      and purpose bred dogs (n = 5; controls). METHODS: The CT features of 32 severely
      incongruent joints with concomitant FCP were compared with those of 32 congruent
      elbow joints affected with FCP and 10 normal joints. RESULTS: In severely
      incongruent elbow joints, a radioulnar step and widened joint spaces were visible
      on each CT plane. Additional features typically seen in severely incongruent
      elbows were a cyst at the radioulnar transition and fragmentation of the axial
      border of the medial coronoid incisure. None of these features appeared in normal
      or in congruent FCP joints. CONCLUSION: On CT, several features associated with
      severe elbow incongruity and concomitant FCP were detected, which were not found
      in normal joints or congruent joints affected by FCP.

PMID- 22613017
TI  - Synovitis in dogs with stable stifle joints and incipient cranial cruciate
      ligament rupture.

PMID- 22613018
TI  - Conservative versus arthroscopic management for medial coronoid process disease
      in dogs: a prospective gait evaluation.

PMID- 22613019
TI  - Molecular validation of the acute phencyclidine rat model for schizophrenia:
      identification of translational changes in energy metabolism and
      neurotransmission.
AB  - Administration of the noncompetitive N-methyl-D-aspartate (NMDA) receptor
      antagonist phencyclidine (PCP) to rodents is widely used as preclinical model for
      schizophrenia. Most studies on this model employ methods investigating behavior
      and brain abnormalities. However, little is known about the corresponding
      peripheral effects. In this study, we analyzed changes in brain and serum
      molecular profiles, together with alterations in behavior after acute PCP
      treatment of rats. Furthermore, abnormalities in peripheral protein expression of
      first and recent onset antipsychotic free schizophrenia patients were assessed
      for comparison with the preclinical model. PCP treatment induced hyperlocomotion
      and stereotypic behavior, which have been related to positive symptoms of
      schizophrenia. Multiplex immunoassay profiling of serum revealed molecular
      abnormalities similar to those seen in first and recent onset, antipsychotic free
      schizophrenia patients. Also, increased insulin levels were detected after
      administration of a glucose tolerance test (GTT), consistent with previous
      studies showing changes in insulin signaling in patients with schizophrenia.
      Finally, schizophrenia-relevant alterations in brain molecules were found in the
      hippocampus and to a lesser extent in the frontal cortex using liquid
      chromatography mass spectrometry and (1)H nuclear magnetic resonance
      spectroscopy. In conclusion, this study identified behavioral and molecular
      alterations in the acute PCP rat model, which are also observed in human
      schizophrenia. We propose that the corresponding changes in serum in both animals
      and patients may have utility as surrogate markers in this model to facilitate
      discovery and development of novel drugs for treatment of certain pathological
      features of schizophrenia.

PMID- 22613020
TI  - Trait-affect, depressed mood, and male sexual functioning: a preliminary study.
AB  - INTRODUCTION: The relationship between trait-affect, depressed mood, and sexual
      functioning has been studied; however, the nature of that relation is not yet
      well established. AIM: The aim of the present study was to investigate the
      mediator role that depressed mood plays in the relation between trait-affect and
      sexual functioning in men. METHODS: A total of 205 men from the general
      population participated in the study and completed self-reported measures
      assessing trait-affect, depressed mood, and sexual functioning. MAIN OUTCOME
      MEASURES: Trait-affect was measured by the Positive Affect-Negative Affect Scale
      Expanded Version, depressed mood was assessed by the Beck Depression Inventory,
      and male sexual function was measured by the International Index of Erectile
      Function. RESULTS: Regression analysis showed that negative trait-affect and
      depressed mood were significant predictors of sexual functioning. Moreover,
      mediation analyses indicated that depressed mood partially mediate the
      relationship between negative trait-affect and sexual functioning in men.
      CONCLUSION: Findings support the role of negative trait-affect and depressed mood
      on male sexual functioning.

PMID- 22613021
TI  - The effects of L-NAME on neuronal NOS and SOD1 expression in the DRG-spinal cord
      network of axotomised Thy 1.2 eGFP mice.
AB  - Nitric oxide (NO) plays an important role in pathophysiology of the nervous
      system. Copper/zinc superoxide dismutase (SOD1) reacts with superoxide, which is
      also a substrate for NO, to provide antioxidative protection. NO production is
      greatly altered following nerve injury, therefore we hypothesised that SOD1 and
      NO may be involved in modulating axotomy responses in dorsal root ganglion (DRG)
      spinal network. To investigate this interaction, adult Thy1.2 enhanced membrane
      bound green fluorescent protein (eGFP) mice underwent sciatic nerve axotomy and
      received NG-nitro- <l-arginine methylester (L-NAME) or vehicle 7-9 days later. L4
      L6 spinal cord and DRG were harvested for immunohistochemical analyses. Effect of
      injury was confirmed by axotomy markers; small proline-rich repeat protein 1A
      (SPRR1A) was restricted to ipsilateral neuropathology, while Thy1.2 eGFP revealed
      also contralateral crossover effects. L-NAME, but not axotomy, increased neuronal
      NO synthase (nNOS) and SOD1 immunoreactive neurons, with no colocalisation, in a
      lamina-dependent manner in the dorsal horn of the spinal cord. Axotomy and/or L
      NAME had no effect on total nNOS+ and SOD1+ neurons in DRG. However, L-NAME
      altered SOD1 expression in subsets of axotomised DRG neurons. These findings
      provide evidence for differential distribution of SOD1 and its modulation by NO,
      which may interact to regulate axotomy-induced changes in DRG-spinal network.

PMID- 22613023
TI  - Innate imprinting of murine resident alveolar macrophages by allergic bronchial
      inflammation causes a switch from hypoinflammatory to hyperinflammatory
      reactivity.
AB  - Resident alveolar macrophages (rAMs) residing in the bronchoalveolar lumen of the
      airways play an important role in limiting excessive inflammatory responses in
      the respiratory tract. High phagocytic activity along with hyporesponsiveness to
      inflammatory insults and lack of autonomous IFN-beta production are crucial
      assets in this regulatory function. Using a mouse model of asthma, we analyzed
      the fate of rAMs both during and after allergic bronchial inflammation. Although
      nearly indistinguishable phenotypically from naive rAMs, postinflammation rAMs
      exhibited a strongly reduced basal phagocytic capacity, accompanied by a markedly
      increased inflammatory reactivity to Toll-like receptors TLR-3 (poly I:C), TLR-4
      [lipopolysaccharide (LPS)], and TLR-7 (imiquimod). Importantly, after
      inflammation, rAMs exhibited a switch from an IFN-beta-defective to an IFN-beta
      competent phenotype, thus indicating the occurrence of a new, inflammatory
      released rAM population in the postallergic lung. Analysis of rAM turnover
      revealed a rapid disappearance of naive rAMs after the onset of inflammation.
      This inflammation-induced rAM turnover is critical for the development of the
      hyperinflammatory rAM phenotype observed after clearance of bronchial
      inflammation. These data document a novel mechanism of innate imprinting in which
      noninfectious bronchial inflammation causes alveolar macrophages to acquire a
      highly modified innate reactivity. The resulting increase in secretion of
      inflammatory mediators on TLR stimulation implies a role for this phenomenon of
      innate imprinting in the increased sensitivity of postallergic lungs to
      inflammatory insults.

PMID- 22613024
TI  - Ectonucleotide triphosphate diphosphohydrolase-1 (CD39) mediates resistance to
      occlusive arterial thrombus formation after vascular injury in mice.
AB  - Modulation of purinergic signaling, which is critical for vascular homeostasis
      and the response to vascular injury, is regulated by hydrolysis of
      proinflammatory ATP and/or ADP by ectonucleoside triphosphate diphosphohydrolase
      1 (ENTPD-1; CD39) to AMP, which then is hydrolyzed by ecto-5'-nucleotidase (CD73)
      to adenosine. We report here that compared with littermate controls (wild type),
      transgenic mice expressing human ENTPDase-1 were resistant to the formation of an
      occlusive thrombus after FeCl(3)-induced carotid artery injury. Treatment of mice
      with the nonhydrolyzable ADP analog, adenosine-5'-0-(2-thiodiphosphate)
      trilithium salt, Ado-5'-PP[S], negated the protection from thrombosis, consistent
      with a role for ADP in platelet recruitment and thrombus formation. ENTPD-1
      expression decreased whole-blood aggregation after stimulation by ADP, an effect
      negated by adenosine-5'-0-(2-thiodiphosphate) trilithium salt, Ado-5'-PP[S]
      stimulation, and limited the ability to maintain the platelet fibrinogen
      receptor, glycoprotein alpha(IIb)/beta(3), in a fully activated state, which is
      critical for thrombus formation. In vivo treatment with a CD73 antagonist, a
      nonselective adenosine-receptor antagonist, or a selective A(2A) or A(2B)
      adenosine-receptor antagonist, negated the resistance to thrombosis in transgenic
      mice expressing human ENTPD-1, suggesting a role for adenosine generation and
      engagement of adenosine receptors in conferring in vivo resistance to occlusive
      thrombosis in this model. In summary, our findings identify ENTPDase-1 modulation
      of purinergic signaling as a key determinant of the formation of an occlusive
      thrombus after vascular injury.

PMID- 22613025
TI  - The regulatory roles of apoptosis-inducing factor in the formation and regression
      processes of ocular neovascularization.
AB  - The role of apoptosis in the formation and regression of neovascularization is
      largely hypothesized, although the detailed mechanism remains unclear.
      Inflammatory cells and endothelial cells both participate and interact during
      neovascularization. During the early stage, these cells may migrate into an
      angiogenic site and form a pro-angiogenic microenvironment. Some angiogenic
      vessels appear to regress, whereas some vessels mature and remain. The control
      mechanisms of these processes, however, remain unknown. Previously, we reported
      that the prevention of mitochondrial apoptosis contributed to cellular survival
      via the prevention of the release of proapoptotic factors, such as apoptosis
      inducing factor (AIF) and cytochrome c. In this study, we investigated the
      regulatory role of cellular apoptosis in angiogenesis using two models of ocular
      neovascularization: laser injury choroidal neovascularization and VEGF-induced
      corneal neovascularization in AIF-deficient mice. Averting apoptosis in AIF
      deficient mice decreased apoptosis of leukocytes and endothelial cells compared
      to wild-type mice and resulted in the persistence of these cells at angiogenic
      sites in vitro and in vivo. Consequently, AIF deficiency expanded
      neovascularization and diminished vessel regression in these two models. We also
      observed that peritoneal macrophages from AIF-deficient mice showed anti
      apoptotic survival compared to wild-type mice under conditions of starvation. Our
      data suggest that AIF-related apoptosis plays an important role in
      neovascularization and that mitochondria-regulated apoptosis could offer a new
      target for the treatment of pathological angiogenesis.

PMID- 22613026
TI  - Contribution of stem cells to neointimal formation of decellularized vessel
      grafts in a novel mouse model.
AB  - Artificial vessel grafts are often used for the treatment of occluded blood
      vessels, but neointimal lesions commonly occur. To both elucidate and quantify
      which cell types contribute to the developing neointima, we established a novel
      mouse model of restenosis by grafting a decellularized vessel to the carotid
      artery. Typically, the graft developed neointimal lesions after 2 weeks,
      resulting in lumen closure within 4 weeks. Immunohistochemical staining revealed
      the presence of endothelial and smooth muscle cells, monocytes, and
      stem/progenitor cells at 2 weeks after implantation. Explanted cultures of
      neointimal tissues displayed heterogeneous outgrowth in stem cell medium. These
      lesional cells expressed a panel of stem/progenitor markers, including c-kit,
      stem cell antigen-1 (Sca-1), and CD34. Furthermore, these cells showed clonogenic
      and multilineage differentiation capacities. Isolated Sca-1(+) cells were able to
      differentiate into endothelial and smooth muscle cells in response to vascular
      endothelial growth factor (VEGF) or platelet-derived growth factor (PDGF)-BB
      stimulation in vitro. In vivo, local application of VEGF to the adventitial side
      of the decellularized vessel increased re-endothelialization and reduced
      neointimal formation in samples at 4 weeks after implantation. A population of
      stem/progenitor cells exists within developing neointima, which displays the
      ability to differentiate into both endothelial and smooth muscle cells and can
      contribute to restenosis. Our findings also indicate that drugs or cytokines that
      direct cell differentiation toward an endothelial lineage may be effective tools
      in the prevention or delay of restenosis.

PMID- 22613028
TI  - A revised health impact assessment of increased use of aspirin in Wales.

PMID- 22613029
TI  - Memetic algorithms for de novo motif-finding in biomedical sequences.
AB  - OBJECTIVES: The objectives of this study are to design and implement a new
      memetic algorithm for de novo motif discovery, which is then applied to detect
      important signals hidden in various biomedical molecular sequences. METHODS AND
      MATERIALS: In this paper, memetic algorithms are developed and tested in de novo
      motif-finding problems. Several strategies in the algorithm design are employed
      that are to not only efficiently explore the multiple sequence local alignment
      space, but also effectively uncover the molecular signals. As a result, there are
      a number of key features in the implementation of the memetic motif-finding
      algorithm (MaMotif), including a chromosome replacement operator, a chromosome
      alteration-aware local search operator, a truncated local search strategy, and a
      stochastic operation of local search imposed on individual learning. To test the
      new algorithm, we compare MaMotif with a few of other similar algorithms using
      simulated and experimental data including genomic DNA, primary microRNA sequences
      (let-7 family), and transmembrane protein sequences. RESULTS: The new memetic
      motif-finding algorithm is successfully implemented in C++, and exhaustively
      tested with various simulated and real biological sequences. In the simulation,
      it shows that MaMotif is the most time-efficient algorithm compared with others,
      that is, it runs 2 times faster than the expectation maximization (EM) method and
      16 times faster than the genetic algorithm-based EM hybrid. In both simulated and
      experimental testing, results show that the new algorithm is compared favorably
      or superior to other algorithms. Notably, MaMotif is able to successfully
      discover the transcription factors' binding sites in the chromatin
      immunoprecipitation followed by massively parallel sequencing (ChIP-Seq) data,
      correctly uncover the RNA splicing signals in gene expression, and precisely find
      the highly conserved helix motif in the transmembrane protein sequences, as well
      as rightly detect the palindromic segments in the primary microRNA sequences.
      CONCLUSIONS: The memetic motif-finding algorithm is effectively designed and
      implemented, and its applications demonstrate it is not only time-efficient, but
      also exhibits excellent performance while compared with other popular algorithms.

PMID- 22613027
TI  - Spontaneous skin erosions and reduced skin and corneal wound healing characterize
      CLIC4(NULL) mice.
AB  - Cutaneous wound healing is a complex process involving blood clotting,
      inflammation, migration of keratinocytes, angiogenesis, and, ultimately, tissue
      remodeling and wound closure. Many of these processes involve transforming growth
      factor-beta (TGF-beta) signaling, and mice lacking components of the TGF-beta
      signaling pathway are defective in wound healing. We show herein that CLIC4, an
      integral component of the TGF-beta pathway, is highly up-regulated in skin
      wounds. We genetically deleted murine CLIC4 and generated a colony on a C57Bl/6
      background. CLIC4(NULL) mice were viable and fertile but had smaller litters than
      did wild-type mice. After 6 months of age, up to 40% of null mice developed
      spontaneous skin erosions. Reepithelialization of induced full-thickness skin
      wounds and superficial corneal wounds was delayed in CLIC4(NULL) mice, resolution
      of inflammation was delayed, and expression of beta4 integrin and p21 was reduced
      in lysates of constitutive and wounded CLIC4(NULL) skin. The induced level of
      phosphorylated Smad2 in response to TGF-beta was reduced in cultured CLIC4(NULL)
      keratinocytes relative to in wild-type cells, and CLIC4(NULL) keratinocytes
      migrated slower than did wild-type keratinocytes and did not increase migration
      in response to TGF-beta. CLIC4(NULL) keratinocytes were also less adherent on
      plates coated with matrix secreted by wild-type keratinocytes. These results
      indicate that CLIC4 participates in skin healing and corneal wound
      reepithelialization through enhancement of epithelial migration by a mechanism
      that may involve a compromised TGF-beta pathway.

PMID- 22613030
TI  - Reciprocal inhibition post-stroke is related to reflex excitability and movement
      ability.
AB  - OBJECTIVE: Decreased reciprocal inhibition (RI) of motor neurons may contribute
      to spasticity after stroke. However, decreased RI is not a uniform observation
      among stroke survivors, suggesting that this spinal circuit may be influenced by
      other stroke-related characteristics. The purpose of this study was to measure RI
      post-stroke and to examine the relationship between RI and other features of
      stroke. METHODS: RI was examined in 15 stroke survivors (PAR) and 10 control
      subjects by quantifying the effect of peroneal nerve stimulation on soleus H
      reflex amplitude. The relationship between RI and age, time post-stroke, lesion
      side, walking velocity, Fugl-Meyer, Ashworth, and Achilles reflex scores was
      examined. RESULTS: RI was absent and replaced by reciprocal facilitation in 10 of
      15 PAR individuals. Reciprocal facilitation was associated with low Fugl-Meyer
      scores and slow walking velocities but not with hyperactive Achilles tendon
      reflexes. There was no relationship between RI or reciprocal facilitation and
      time post-stroke, lesion side, or Ashworth score. CONCLUSIONS: Decreased RI is
      not a uniform finding post-stroke and is more closely related to walking ability
      and movement impairment than to spasticity. SIGNIFICANCE: Phenomena other than
      decreased RI may contribute to post-stroke spasticity.

PMID- 22613031
TI  - Arsenic impairs embryo development via down-regulating Dvr1 expression in
      zebrafish.
AB  - Exposure to environmental inorganic arsenic compounds has serious health effects
      on humans, including cancer, cardiovascular disease, developmental and
      reproductive problems. Our previous study showed that arsenic exposure caused
      various signs of toxicity in early stages of zebrafish development, including
      cardiac and neural system, such as pericardium edema, circulation failure, heart
      malformation. However, how arsenic exerts these effects is little known. Here,
      real-time quantitative RT-PCR and whole-mount in situ hybridization data showed
      that zebrafish Dvr1, a mammalian homolog of GDF1 related to the formation of left
      right axis, was significantly down-regulated in embryos exposed to arsenite.
      Embryos with Dvr1 knockdown by antisense morpholino displayed abnormal
      development, including pericardium edema and failed looping, which is similar to
      the defects phenotype with arsenic treatment. Furthermore, overexpression of GDF1
      significantly rescued development anomalies caused by morpholino or arsenite.
      Taken together, our results indicated for the first time that Dvr1 played an
      important role in the left-right asymmetry establishment of zebrafish embryo, and
      Dvr1 was involved in arsenic-mediated embryo toxicity, which gives novel insight
      into molecular mechanism of arsenic-mediated embryo toxicity.

PMID- 22613032
TI  - Immunocytological and biochemical analysis of the mode of action of bis (tri-n
      butyltin) tri-oxide (TBTO) in Jurkat cells.
AB  - Bis (tri-n-butyltin) oxide (TBTO) is one of the organotin compounds known to
      induce immunosuppression. Previously, we examined the effect of TBTO on whole
      genome mRNA expression in the human T lymphocyte cell line Jurkat, which led to
      the hypothesis that induction of endoplasmic reticulum (ER) stress is the first
      initiated event, which induces a rise of intracellular calcium levels, activation
      of NF-kB and NFAT, T cell activation response and oxidative stress together
      finally resulting in apoptosis. The present study verified this hypothesis with
      biochemical and cytological experiments. The induction of ER stress was confirmed
      by the rapid raise in protein levels of ATF3 and DDIT3. Moreover, the impairment
      of cell viability by TBTO was moderated by the ER stress inhibitor phenyl butyric
      acid. Real-time fluorescence microscopy confirmed that TBTO increases
      intracellular calcium levels within 2min of exposure. Furthermore, the
      involvement of increased calcium levels in the effects of TBTO was evident from
      the induction of three calcium-dependent events: (1) activation of the protease
      activity of M-calpain, (2) induction of NF-kB (p65) expression, and (3)
      activation of NFAT. The induction of oxidative stress was verified by detection
      of increased levels of reactive oxygen species and a decrease in amount of
      reduced glutathione. We also showed that TBTO induces cleavage of caspase-3, an
      event known to mediate apoptosis. Finally, comparative microarray data analysis
      showed that many of the processes observed in vitro also occur in vivo in
      thymuses of TBTO-treated mice.

PMID- 22613033
TI  - Oxytocin selectively moderates negative cognitive appraisals in high trait
      anxious males.
AB  - The mammalian neuropeptide oxytocin has well-characterized effects in
      facilitating prosocial and affiliative behavior. Additionally, oxytocin decreases
      physiological and behavioral responses to social stress. In the present study we
      investigated the effects of oxytocin on cognitive appraisals after a naturalistic
      social stress task in healthy male students. In a randomized, double-blind,
      placebo-controlled trial, 48 participants self-administered either an oxytocin or
      placebo nasal spray and, following a wait period, completed an impromptu speech
      task. Eye gaze to a pre-recorded video of an audience displayed during the task
      was simultaneously collected. After the speech, participants completed
      questionnaires assessing negative cognitive beliefs about speech performance.
      Whilst there was no overall effect of oxytocin compared to placebo on either eye
      gaze or questionnaire measures, there were significant positive correlations
      between trait levels of anxiety and negative self-appraisals following the
      speech. Exploratory analyses revealed that whilst higher trait anxiety was
      associated with increasingly poorer perceptions of speech performance in the
      placebo group, this relationship was not found in participants administered
      oxytocin. These results provide preliminary evidence to suggest that oxytocin may
      reduce negative cognitive self-appraisals in high trait anxious males. It adds to
      a growing body of evidence that oxytocin seems to attenuate negative cognitive
      responses to stress in anxious individuals.

PMID- 22613034
TI  - Neonatal tryptophan depletion and corticosterone supplementation modify emotional
      responses in adult male mice.
AB  - The serotonergic system and the hypothalamic-pituitary-adrenal (HPA) axis are
      crucially involved in the regulation of emotions. Specifically, spontaneous
      and/or environmentally mediated modulations of the functionality of these systems
      early in development may favour the onset of depressive- and anxiety-related
      phenotypes. While the independent contribution of each of these systems to the
      emergence of abnormal phenotypes has been detailed in clinical and experimental
      studies, only rarely has their interaction been systematically investigated.
      Here, we addressed the effects of reduced serotonin and environmental stress
      during the early stages of postnatal life on emotional regulations in mice. To
      this aim, we administered, to outbred CD1 mouse dams, during their first week of
      lactation, a tryptophan deficient diet (T) and corticosterone via drinking water
      (C; 80MUg/ml). Four groups of dams (animal facility rearing, AFR; T treated, T; C
      treated, C; T and C treated, TC) and their male offspring were used in the study.
      Maternal care was scored throughout treatment and adult offspring were tested
      for: anhedonia (progressive ratio schedule); anxiety-related behaviour (approach
      avoidance conflict paradigm); BDNF, dopamine and serotonin concentrations in
      selected brain areas. T, C and TC treatments reduced active maternal care
      compared to AFR. Adult TC offspring showed significantly increased anxiety- and
      anhedonia-related behaviours, reduced striatal and increased hypothalamic BDNF
      and reduced dopamine and serotonin in the prefrontal cortex and their turnover in
      the hippocampus. Thus, present findings support the view that neonatal variations
      in the functionality of the serotonergic system and of HPA axis may jointly
      contribute to induce emotional disturbances in adulthood.

PMID- 22613035
TI  - Day and nighttime excretion of 6-sulphatoxymelatonin in adolescents and young
      adults with autistic disorder.
AB  - BACKGROUND: Several reports indicate that nocturnal production of melatonin is
      reduced in autism. Our objective was to examine whether melatonin production is
      decreased during the whole 24-h cycle, whether the melatonin circadian rhythm is
      inverted, and whether the reduction in melatonin production is related to the
      severity of autistic behavioral impairments. METHOD: Day and nighttime urinary
      excretion of 6-sulphatoxymelatonin (6-SM) was examined during a 24-h period in
      post-pubertal individuals with autism (N=43) and typically developing controls
      (N=26) matched for age, sex and pubertal stage. RESULTS: Low 6-SM excretion (mean
      +/- SEM) was observed in autism, both at daytime (0.16 +/- 0.03 vs. 0.36 +/- 0.05
      MUg/h, p<0.01), nighttime (0.52 +/- 0.07 vs. 1.14 +/- 0.23 MUg/h, p<0.05), and
      during 24h (8.26 +/- 1.27 vs. 18.00 +/- 3.43 MUg/24-h collection, p<0.001). Intra
      individual nighttime-daytime differences (delta values) in 6-SM excretion were
      smaller in individuals with autism than in controls (0.36 +/- 0.07 vs. 0.79 +/-
      0.23 MUg/h, p<0.05). Nocturnal excretion of 6-SM was negatively correlated with
      autism severity in the overall level of verbal language (Spearman rho=-0.30,
      p<0.05), imitative social play (Spearman rho=-0.42, p<0.05), and repetitive use
      of objects (Spearman rho=-0.36, p<0.05). CONCLUSION: A deficit in melatonin
      production is present both at daytime and at nighttime in individuals with
      autism, particularly in the most severely affected individuals. These results
      highlight interest in potential therapeutic uses of melatonin in autistic
      disorder, especially in individuals with severe autistic impairment and/or low
      urinary 6-SM excretion.

PMID- 22613036
TI  - Synthesis, characterization and biological evaluation of some novel 17-isoxazoles
      in the estrone series.
AB  - Regioselective 1,3-dipolar cycloadditions of different aryl nitrile oxides to
      mestranol were carried out to furnish novel steroidal 17alpha-isoxazoles in good
      to excellent yields. Copper(I) was found to be an efficient catalyst,
      accelerating the intermolecular ring-closures and leading exclusively to 3,5
      disubstituted isoxazoles. The yields of the cycloadducts, however, were
      influenced by the substituents on the aromatic moiety of the 1,3-dipoles.
      Moreover, dehydration of the primary products resulted in the corresponding
      Delta(16,17)exo-heterocyclic derivatives. All the synthesized compounds were
      subjected to in vitro pharmacological studies of their antiproliferative effects
      relative to three human malignant cell lines (HeLa, MCF7 and A2780).

PMID- 22613038
TI  - Therapeutic platforms based on gold nanoparticles and their covalent conjugates
      with drug molecules.
AB  - This review will first look at the various covalent strategies that have been
      developed to attach drugs to gold nanoparticles as well as the strengths and
      limitations of such strategies. After examining general strategies for the
      synthesis of gold nanoparticles and their subsequent covalent functionalization,
      this review will focus on nanoparticle conjugates for gene therapy,
      antibacterial, and anticancer applications including the use of gold
      nanoparticles with intrinsically therapeutic properties. The effects of targeting
      and cellular uptake of gold nanoparticles will also be discussed.

PMID- 22613037
TI  - Exploring inequalities in access to and use of maternal health services in South
      Africa.
AB  - BACKGROUND: South Africa's maternal mortality rate (625 deaths/100,000 live
      births) is high for a middle-income country, although over 90% of pregnant women
      utilize maternal health services. Alongside HIV/AIDS, barriers to Comprehensive
      Emergency Obstetric Care currently impede the country's Millenium Development
      Goals (MDGs) of reducing child mortality and improving maternal health. While
      health system barriers to obstetric care have been well documented, "patient
      oriented" barriers have been neglected. This article explores affordability,
      availability and acceptability barriers to obstetric care in South Africa from
      the perspectives of women who had recently used, or attempted to use, these
      services. METHODS: A mixed-method study design combined 1,231 quantitative exit
      interviews with sixteen qualitative in-depth interviews with women (over 18) in
      two urban and two rural health sub-districts in South Africa. Between June 2008
      and September 2009, information was collected on use of, and access to, obstetric
      services, and socioeconomic and demographic details. Regression analysis was used
      to test associations between descriptors of the affordability, availability and
      acceptability of services, and demographic and socioeconomic predictor variables.
      Qualitative interviews were coded deductively and inductively using ATLAS ti.6.
      Quantitative and qualitative data were integrated into an analysis of access to
      obstetric services and related barriers. RESULTS: Access to obstetric services
      was impeded by affordability, availability and acceptability barriers. These were
      unequally distributed, with differences between socioeconomic groups and
      geographic areas being most important. Rural women faced the greatest barriers,
      including longest travel times, highest costs associated with delivery, and
      lowest levels of service acceptability, relative to urban residents. Negative
      provider-patient interactions, including staff inattentiveness, turning away
      women in early-labour, shouting at patients, and insensitivity towards those who
      had experienced stillbirths, also inhibited access and compromised quality of
      care. CONCLUSIONS: To move towards achieving its MDGs, South Africa cannot just
      focus on increasing levels of obstetric coverage, but must systematically address
      the access constraints facing women during pregnancy and delivery. More needs to
      be done to respond to these "patient-oriented" barriers by improving how and
      where services are provided, particularly in rural areas and for poor women, as
      well as altering the attitudes and actions of health care providers.

PMID- 22613039
TI  - Theory of EPR lineshape in samples concentrated in paramagnetic spins: effect of
      enhanced internal magnetic field on high-field high-frequency (HFHF) EPR
      lineshape.
AB  - A theoretical treatment is provided for the calculation of EPR (electron
      paramagnetic resonance) lineshape as affected by interactions with paramagnetic
      ions in the vicinity. The internal fields seen by the various paramagnetic ions
      due to interactions with paramagnetic ions in their vicinity, as well as the
      resulting lineshapes, become quite significant at high magnetic fields required
      in high-frequency (HFHF) EPR. The resulting EPR signals for the various ions are
      therefore characterized by different g-shifts and lineshapes, so that the overall
      EPR lineshape, which is an overlap of these, becomes distorted, or even split in
      HFHF EPR, from that observed at lower frequencies. The observed EPR lineshapes in
      MnSO(4)?H(2)O powder and K(3)CrO(8) single-crystal samples have been simulated
      here taking into account g-shifts and modified lineshapes. These simulations show
      that in these samples, concentrated in paramagnetic spins, the position and
      lineshapes of EPR signals are significantly modified in HFHF EPR involving very
      high magnetic fields.

PMID- 22613040
TI  - Paroxysmal complete atrioventricular block during AV nodal reentrant tachycardia.

PMID- 22613041
TI  - Pathological and immunohistochemical study of lethal primary brain stem injuries.
AB  - BACKGROUND: Many of the deaths that occur shortly after injury or in hospitals
      are caused by mild trauma. Slight morphological changes are often found in the
      brain stems of these patients during autopsy. The purpose of this study is to
      investigate the histopathological changes involved in primary brain stem injuries
      (PBSI) and their diagnostic significance. METHODS: A total of 65 patients who had
      died of PBSI and other conditions were randomly selected. They were divided into
      2 groups, an injury group (25 cases) and a control group (20 cases). Slides of
      each patient's midbrain, pons, and medulla oblongata were prepared and stained
      with HE, argentaffin, and immunohistochemical agents (GFAP, NF, amyloid-beta,
      MBP). Under low power (*100) and NF staining, the diameter of the thickest
      longitudinal axon was measured at its widest point. Ten such diameters were
      collected for each part of the brain (midbrain, pons, and medulla oblongata).
      Data were recorded and analyzed statistically. RESULTS: Brain stem contusions,
      astrocyte activity, edema, and pathological changes in the neurons were visibly
      different in the injury and control groups (P < 0.05). Characteristic changes
      occurred in the neural axons, axon diameter varied from axon to axon and even
      over different segments of one axon, and several pathological phenomena were
      observed. These included segmental thickening and curving, wave-like processing,
      disarrangement, and irregular swelling. A few axons ruptured and intumesced into
      retraction balls. Immunohistochemical MBP staining showed enlargement and curving
      of spaces between the myelin sheaths and axons in certain areas. The myelin
      sheaths lining the surfaces of the axons were in some cases incomplete and even
      exfoliated, and segmentation disappeared. These pathological changes increased in
      severity over time (P < 0.05). CONCLUSIONS: These histopathological changes may
      prove beneficial to the pathological diagnosis of PBSI during autopsy. The
      measurement of axon diameters provides a referent quantitative index for the
      diagnosis of the specific causes of death involved in PBSI. VIRTUAL SLIDES: The
      virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1345298818712204.

PMID- 22613042
TI  - Political and civic engagement development in adolescence.

PMID- 22613043
TI  - How is civic engagement developed over time? Emerging answers from a
      multidisciplinary field.
AB  - Insights into the development of civic values, attitudes, knowledge, skills and
      behaviours are greatly demanded by adults worried about a seemingly steady
      decline in the societal interest of their offspring. Hence, the collection of
      studies in this special issue on civic engagement in adolescence is not only
      timely and enlightening, but it also has the potentials to contribute to research
      in different disciplines on various dimensions, mechanisms and normative models
      of civic engagement. The studies reveal some promising attempts to bring civil
      themes into the field of adolescent development. However, to overcome some
      conceptual, methodological and empirical shortcomings, future developmental
      studies in the area need to be substantially improved by considering cultural and
      institutional conditions, by focussing on processes across various everyday life
      contexts, by merging theories from different disciplinary fields, by
      conceptualizing adolescents as changeable subjects, and by delineating untested
      and unwarranted normative assumptions.

PMID- 22613045
TI  - Acute exercise and subsequent nutritional adaptations: what about obese youths?
AB  - The imbalance between energy expenditure and energy intake is the main factor
      accounting for the progression of obesity. For many years, physical activity has
      been part of weight-loss programmes to increase energy expenditure. It is now
      recognized that exercise can also affect appetite and energy consumption. In the
      context of seeking new obesity treatments, it is of major interest to clarify the
      impact of physical exercise on energy intake. Many reviews on this topic have
      been published regarding both lean and overweight adults, and this review focuses
      on the relationships between acute exercise and the short-term regulation of
      energy intake in lean and overweight or obese youths. The current literature
      provides very few data regarding the impact of exercise on subsequent energy
      intake and perceived and measured appetite in children and adolescents, mainly
      because of methodological difficulties in the assessment of both energy intake
      and expenditure. It has been long suggested that energy intake was regulated
      after exercise in order to compensate for the exercise-induced energy expenditure
      and then preserve energy balance. This overview underlines that the energy
      expended during exercise is not the main parameter that influences subsequent
      energy intake in both lean and overweight/obese children and adolescents, and
      that factors such as the duration or intensity of exercise may have larger
      impact. The effects of acute exercise on the following nutritional adaptations
      (energy intake and appetite feelings) remain inconclusive in lean youths, mainly
      due to the lack of data and the disparity of the methodologies used. Studies in
      overweight or obese children and adolescents are confronted with the same
      difficulties, and the few available data suggest that intensive exercise (>70%
      maximal oxygen consumption) can induce a reduction in daily energy balance, as a
      result of its anorexigenic effect in obese adolescents. However, further studies
      are needed to clarify the impact of acute exercise on subsequent nutritional
      adaptations and appetite-related hormones in children and adolescents, and to
      investigate the effect of chronic exercise programmes.

PMID- 22613046
TI  - Challenges associated with central venous catheter placement and central venous
      oxygen saturation monitoring.

PMID- 22613048
TI  - The potential of volunteers to implement non-pharmacological interventions to
      reduce agitation associated with dementia in nursing home residents.
AB  - BACKGROUND: Advanced dementia may be accompanied by behavioral and psychological
      symptoms of dementia (BPSD). BPSD stemming from pain, depression, or psychosis
      benefit from treatment with drugs, but in other cases, medications have limited
      efficacy and may elicit adverse effects. Therefore, more attention has been paid
      to non-pharmacological interventions, which have fewer risks and can be
      successful in reducing agitation and negative mood. However, these interventions
      are frequently not implemented in nursing homes due to staffing constraints. This
      study explores the potential of volunteers to further assist staff. METHODS: We
      interviewed 18 staff members and 39 volunteers in 17 aged care facilities in
      southeast Melbourne, Australia. RESULTS: Three-quarters of the facilities in this
      region worked with at least one regular volunteer. Both self-interest and
      altruistic reasons were identified as motives for volunteering. Volunteers were
      perceived by facility representatives as helpful to residents through provision
      of stimulation and company. However, they were discouraged from engaging with
      individuals with prominent BPSD. A majority of facility representatives and
      volunteers had experienced some difficulties in negotiating working relationships
      but most were easily resolved. A large majority of volunteers expressed an
      interest in learning new methods of interacting with residents. CONCLUSION:
      Despite their beneficial effects for agitated residents, non-pharmacological
      interventions are often not implemented in aged care facilities. Staff members
      often lack time but current volunteers in the sector are available, experienced,
      and interested in learning new methods of interacting. Volunteers therefore
      potentially are a valuable resource to assist with the application of new
      treatments.

PMID- 22613044
TI  - Local activation of cardiac stem cells for post-myocardial infarction cardiac
      repair.
AB  - The prognosis of patients with myocardial infarction (MI) and resultant chronic
      heart failure remains extremely poor despite continuous advancements in optimal
      medical therapy and interventional procedures. Animal experiments and clinical
      trials using adult stem cell therapy following MI have shown a global improvement
      of myocardial function. The emergence of stem cell transplantation approaches has
      recently represented promising alternatives to stimulate myocardial regeneration.
      Regarding their tissue-specific properties, cardiac stem cells (CSCs) residing
      within the heart have advantages over other stem cell types to be the best cell
      source for cell transplantation. However, time-consuming and costly procedures to
      expanse cells prior to cell transplantation and the reliability of cell culture
      and expansion may both be major obstacles in the clinical application of CSC
      based transplantation therapy after MI. The recognition that the adult heart
      possesses endogenous CSCs that can regenerate cardiomyocytes and vascular cells
      has raised the unique therapeutic strategy to reconstitute dead myocardium via
      activating these cells post-MI. Several strategies, such as growth factors,
      mircoRNAs and drugs, may be implemented to potentiate endogenous CSCs to repair
      infarcted heart without cell transplantation. Most molecular and cellular
      mechanism involved in the process of CSC-based endogenous regeneration after MI
      is far from understanding. This article reviews current knowledge opening up the
      possibilities of cardiac repair through CSCs activation in situ in the setting of
      MI.

PMID- 22613047
TI  - Explanatory value of the Ability Index as assessed by cardiologists and patients
      with congenital heart disease.
AB  - INTRODUCTION: The Ability Index was developed to classify patients with
      congenital heart disease into four functional classes. Functional class is
      typically determined by the cardiologist, based on data from a clinical
      interview. The validity of the Ability Index as assessed by the patient has never
      been scrutinized. OBJECTIVE: We tested the agreement between cardiologists and
      patients in assessing functional status using the Ability Index and compared the
      accuracy of the two assessments in explaining patient-reported outcomes (PRO).
      METHODS: The Ability Index Scale was completed for 57 patients, independently by
      cardiologists and patients. Cohen's Kappa coefficient with quadratic weighting
      (K(w)) was calculated. The area under the receiver operating characteristic (ROC)
      curve (AUC) (=C-index) was used to test the accuracy of the Ability Index in
      explaining PRO, as assessed by the cardiologist or the patient. RESULTS:
      Agreement was observed in 61.4% of the patients. The K(w) was 0.55, showing a
      moderate agreement; and the R(2) was 0.29, displaying a limited shared variance.
      The AUC for cardiologists' assessments of the Ability Index in explaining PRO was
      consistently lower than the AUC for patients' assessments. The appraisal of the
      patients was more accurate. DISCUSSION: When cardiologists and patients are
      assessing functional status using the Ability Index, two different constructs are
      measured. These assessments cannot be interchanged, but should be used
      complementarily. Because the assessment of the patients regarding the Ability
      Index is more precise in terms of explaining PRO, it could be valuable as a
      simple crude marker to identify patients at risk for poor functional and
      psychosocial outcomes.

PMID- 22613049
TI  - An anti-inflammatory and anti-microbial flavone glycoside from flowers of Cleome
      viscosa.
AB  - BACKGROUND: Natural products isolated from plant sources have been demonstrated
      as potential candidates against several ailments. The scientific investigations
      on the underlying principles of phytotherapy can pave way for the convergence of
      traditional medicines and modern science and technologies. RESULTS: Quercetin 3-O
      (2''-acetyl)-glucoside obtained from ethyl acetate fraction of Cleome viscosa is
      studied against inflammatory of carrageenan-induced rat paw edema ( in vivo) and
      microbial activity on ( in vitro). The structure of the glycoside is confirmed by
      means of hydrogen-1 nuclear magnetic resonance spectroscopy, carbon nuclear
      magnetic resonance spectroscopy, attached proton test, and mass spectrum. The
      flavonoid glycoside showed significant anti-inflammatory activity of on
      carrageenan-induced rat paw edema ( in vivo) and anti-microbial activity ( in
      vitro) on Staphylococcus aureus (gram positive) and Escherichia coli (gram
      negative). The anti-inflammatory effect of the flavonoid glycoside may be due to
      the inhibition of prostaglandin synthesis. Selective toxicity with flavonoid
      glycoside towards the gram-positive bacteria was found on S. aureus. CONCLUSIONS:
      The present study reveals the anti-inflammatory and antimicrobial activities of
      an isolated quercetin 3-O-(2''-acetyl)-glucoside from a natural source ( C.
      viscosa).

PMID- 22613050
TI  - PDEI-5 for erectile dysfunction: a potential role in seizure susceptibility.
AB  - INTRODUCTION: There is a high prevalence of erectile dysfunction (ED) in men with
      epilepsy; however, few studies have been conducted concerning the treatment of ED
      in this neurological group. AIM: The main purpose of this review is to highlight
      the influence of phosphodiesterase type 5 inhibitor (PDEI-5) for ED on seizure
      susceptibility. METHODS: All available online articles with information
      pertaining to PDEI-5 and seizure susceptibility were included in this review.
      MAIN OUTCOME MEASURES: The main outcome assessed demonstrated the intriguing role
      of PDEI-5 and its metabolites on seizure susceptibility. RESULTS: Case reports in
      men without epilepsy described seizure occurrence and electrophysiological
      changes following sildenafil, tadalafil, or vardenafil treatment. Consistent with
      these findings, preclinical studies suggested a proconvulsant effect of PDEI-5 on
      models of seizure induction. CONCLUSIONS: Evidence suggests an influence of PDEI
      5 on seizure susceptibility in humans. In addition, preclinical studies have
      demonstrated the role of nitric oxide metabolites in the facilitation of
      paroxysmal phenomenon. Although there are many causes of seizures, medical
      professionals should be aware of the possible influence of PDEI-5 on seizure
      susceptibility. Further investigation by physicians and scientists is required to
      improve our understanding of this important topic.

PMID- 22613052
TI  - QM/MM study of catalytic mechanism of Xylanase Cex from Cellulomonas fimi.
AB  - Xylanase Cex from Cellulomonas fimi is a bifunctional enzyme that catalyzes the
      degradation of both cellulose and xylan. As a result, it might find valuable
      applications in production of biofuels. In this work, we presented a detailed
      theoretical investigation of hydrolysis of the xylopentaose molecule catalyzed by
      Cex, using a hybrid quantum mechanical and molecular mechanical approach. Our
      results support the experimental observation that the hydrolysis proceeds via the
      net retention mechanism. More interestingly, our simulations indicate that the
      xylose unit at -1 binding site should take a boat (B2,5) conformation as a
      possible reactive conformer, while the oxo-carbenium ion-like transition states
      take the combination of B2,5/0S2 for glycosylation, and 0S2/0,3B for
      deglycosylation. Our molecular dynamics simulations of mutants further suggest
      that two catalytic residues (E127 and E233) play the vital role in this ring
      distortion. Indeed, this conformational change is necessary to facilitate the
      first step of nucleophilic attack by E233 at the anomeric carbon center.

PMID- 22613051
TI  - [Right adrenal metastasis that required replacement of the infrahepatic vena
      cava].

PMID- 22613053
TI  - Detection of bioavailable peroxisome proliferator-activated receptor gamma
      modulators by a cell-based luciferase reporter system.
AB  - In vitro cell-based reporter assays are a useful tool for the discovery and
      characterization of nuclear receptor modulators. However, the properties of a
      given molecule can differ when tested in vitro and in vivo as a result of the
      molecule's bioavailability. In this work, we describe a methodology that allows
      the detection of the PPARgamma (peroxisome proliferator-activated receptor gamma)
      agonist bezafibrate in rat serum by an in vitro cell-based reporter assay. This
      methodology could be adapted to the detection and characterization of
      bioavailable PPARgamma or other nuclear receptor modulators in serum, extending
      the possibilities of the classical in vitro assays.

PMID- 22613055
TI  - Functions of microglia in the central nervous system--beyond the immune response.
AB  - Microglia cells are the immune cells of the central nervous system and
      consequently play important roles in brain infections and inflammation. Recent in
      vivo imaging studies have revealed that in the resting healthy brain, microglia
      are highly dynamic, moving constantly to actively survey the brain parenchyma.
      These active microglia can rapidly respond to pathological insults, becoming
      activated to induce a range of effects that may contribute to both pathogenesis,
      or to confer neuronal protection. However, interactions between microglia and
      neurons are being recognized as important in shaping neural circuit activity
      under more normal, physiological conditions. During development and neurogenesis,
      microglia interactions with neurons help to shape the final patterns of neural
      circuits important for behavior and with implications for diseases. In the mature
      brain, microglia can respond to changes in sensory activity and can influence
      neuronal activity acutely and over the long term. Microglia seem to be
      particularly involved in monitoring the integrity of synaptic function. In this
      review, we discuss some of these new insights into the involvement of microglia
      in neural circuits.

PMID- 22613054
TI  - Evaluation of buspirone for relapse-prevention in adults with cocaine dependence:
      an efficacy trial conducted in the real world.
AB  - Cocaine dependence is a significant public health problem for which there are
      currently no FDA-approved medications. Hence, identifying candidate compounds and
      employing an efficient evaluation process is crucial. This paper describes key
      design decisions made for a National Institute on Drug Abuse (NIDA) Clinical
      Trials Network (CTN) study that uses a novel two-stage process to evaluate
      buspirone (60 mg/day) for cocaine-relapse prevention. The study includes pilot
      (N=60) and full-scale (estimated N=264) trials. Both trials will be randomized,
      double-blind, and placebo-controlled and both will enroll treatment-seeking
      cocaine-dependent participants engaged in inpatient/residential treatment and
      scheduled for outpatient treatment post-discharge. All participants will receive
      contingency management in which incentives are given for medication adherence as
      evaluated by the Medication Events Monitoring System (MEMS). The primary outcome
      measure is maximum days of continuous cocaine abstinence, as assessed by twice
      weekly urine drug screens (UDS) and self-report, during the 15-week outpatient
      treatment phase. Drug-abuse outcomes include cocaine use as assessed by UDS and
      self-report of cocaine use, other substance use as assessed by UDS and self
      report of substance use (i.e., alcohol and/or illicit drugs), cocaine bingeing,
      HIV risk behavior, quality of life, functioning, and substance abuse treatment
      attendance. Unique aspects of the study include conducting an efficacy trial in
      community treatment programs, a two-stage process to efficiently evaluate
      buspirone, and an evaluation of mediators by which buspirone might exert a
      beneficial effect on relapse prevention.

PMID- 22613056
TI  - Production of endothelial cell-enclosing alginate-based hydrogel fibers with a
      cell adhesive surface through simultaneous cross-linking by horseradish
      peroxidase-catalyzed reaction in a hydrodynamic spinning process.
AB  - We developed an alginate-based hydrogel fiber enabling to enclose endothelial
      cells, degradable on-demand by alginate lyase, and having a cell adhesive
      surface. The hydrogel fiber was obtained by extruding an aqueous solution of 4%
      (w/v) alginate derivative possessing phenolic hydroxyl moieties (Alg-Ph) and
      horseradish peroxidase (HRP) into a flow of aqueous solution containing 0.3 mM
      H(2)O(2) and gelatin derivative possessing Ph moieties (Gelatin-Ph). In the
      process, cross-linking of Alg-Ph resulting in a hydrogel fiber and immobilization
      of Gelatin-Ph on the surface of the hydrogel fiber were simultaneously
      accomplished by an HRP-catalyzed cross-linking reaction between Ph moieties. The
      diameter of the hydrogel fiber and the quantity of immobilized Gelatin-Ph on the
      fiber were controllable by changing the flow rates of the solutions and the
      concentration of HRP in the Alg-Ph-containing solution, respectively. The
      viability of the human endothelial cells enclosed in the hydrogel fibers obtained
      by 10 s of flowing in the H(2)O(2)-containing solution was 87.1%. In addition,
      the cells harvested from the hydrogel fibers through degradation using alginate
      lyase grew on tissue culture dishes in the same fashion as the cells seeded by a
      conventional subculture protocol. Human smooth muscle cells adhered, grew and
      achieved confluence on the surface of the hydrogel fibers. By degrading the
      hydrogel fibers using alginate lyase, a tubular cell construct was successfully
      obtained.

PMID- 22613057
TI  - The Hispanic Americans Baseline Alcohol Survey (HABLAS): the association between
      acculturation, birthplace and alcohol consumption across Hispanic national
      groups.
AB  - Acculturation to U.S. society has been associated with an increase in drinking
      and binge drinking among Hispanics. This paper examines the association between
      acculturation and three drinking-related outcomes: average number of drinks
      consumed, binge drinking, and drinking 12 drinks or more in a single day in four
      major Hispanic national groups. The 2006 Hispanic Americans Baseline Alcohol
      Survey used a multistage cluster sample design to interview 5224 adult Hispanics
      (18+ years) in five selected U.S. metropolitan areas: Miami, New York,
      Philadelphia, Houston, and Los Angeles. The four national groups interviewed
      were: Puerto Ricans, Cuban Americans, Mexican Americans, and South/Central
      Americans. The survey response rate was 76%. Data on drinking behavior were
      collected and the analyses include bivariate and multivariate regression
      techniques. Multivariate analysis did not show an association between
      acculturation and volume of drinking, binge drinking, or drinking 12 or more
      drinks in a single day among men. Acculturation stress, however, was associated
      with drinking 12 or more in a day among men. Among women, high acculturation was
      associated with a higher volume of drinking, and it also interacted with national
      group to increase the likelihood of binge drinking. Acculturation does not have a
      homogeneous effect on drinking across gender and Hispanic national groups. The
      results confirm that acculturation has a more consistent association with
      increased drinking and binge drinking among women than among men. The effect of
      acculturation is therefore gender-specific. This heterogeneity across Hispanic
      national groups must be considered in future research, treatment, and prevention
      efforts.

PMID- 22613058
TI  - Public awareness of income-related health inequalities in Ontario, Canada.
AB  - INTRODUCTION: Continued action is needed to tackle health inequalities in Canada,
      as those of lower income continue to be at higher risk for a range of negative
      health outcomes. There is arguably a lack of political will to implement policy
      change in this respect. As a result, we investigated public awareness of income
      related health inequalities in a generally representative sample of Ontarians in
      late 2010. METHODS: Data were collected from 2,006 Ontario adults using a
      telephone survey. The survey asked participants to agree or disagree with various
      statements asserting that there are or are not health inequalities in general and
      by income in Ontario, including questions pertaining to nine specific conditions
      for which inequalities have been described in Ontario. A multi-stage process
      using binary logistic regression determined whether awareness of health
      inequalities differed between participant subgroups. RESULTS: Almost 73% of this
      sample of Ontarians agreed with the general premise that not all people are
      equally healthy in Ontario, but fewer participants were aware of health
      inequalities between the rich and the poor (53%-64%, depending on the framing of
      the question). Awareness of income-related inequalities in specific outcomes was
      considerably lower, ranging from 18% for accidents to 35% for obesity.
      CONCLUSIONS: This is the first province-wide study in Canada, and the first in
      Ontario, to explore public awareness on health inequalities. Given that political
      will is shaped by public awareness and opinion, these results suggest that
      greater awareness may be required to move the health equity agenda forward in
      Ontario. There is a need for health equity advocates, physicians and researchers
      to increase the effectiveness of knowledge translation activities for studies
      that identify and explore health inequalities.

PMID- 22613059
TI  - High-calorie food-cues impair working memory performance in high and low food
      cravers.
AB  - The experience of food craving can lead to cognitive impairments. Experimentally
      induced chocolate craving exhausts cognitive resources and, therefore, impacts
      working memory, particularly in trait chocolate cravers. In the current study, we
      investigated the effects of exposure to food-cues on working memory task
      performance in a group with frequent and intense (high cravers, n=28) and less
      pronounced food cravings (low cravers, n=28). Participants performed an n-back
      task that contained either pictures of high-calorie sweets, high-calorie savory
      foods, or neutral objects. Current subjective food craving was assessed before
      and after the task. All participants showed slower reaction times and made more
      omission errors in response to food-cues, particularly savory foods. There were
      no differences in task performance between groups. State cravings did not differ
      between groups before the task, but increased more in high cravers compared to
      low cravers during the task. Results support findings about food cravings
      impairing visuo-spatial working memory performance independent of trait cravings.
      They further show that this influence is not restricted to chocolate, but also
      applies to high-calorie savory foods. Limiting working memory capacity may be
      especially crucial in persons who are more prone to high-calorie food-cues and
      experience such cravings habitually.

PMID- 22613060
TI  - The relationship between zinc intake and serum/plasma zinc concentration in
      pregnant and lactating women: a systematic review with dose-response meta
      analyses.
AB  - Recommendations for zinc intake during pregnancy and lactation vary widely across
      Europe. Using data on zinc intake and biomarkers of zinc status reported in
      randomized controlled trials (RCTs) and observational studies can provide
      estimates of dose-response relationships that may be used for underpinning zinc
      reference values. This systematic review included all RCTs, prospective cohort
      studies, nested case-control studies and cross-sectional studies in healthy
      pregnant and lactating populations published by February 2010 which provided data
      on zinc intake and biomarkers of zinc status. An intake-status regression
      coefficient (beta^) was calculated for each individual study and calculated the
      overall pooled beta^ and SE (beta^) using random effects meta-analysis on a
      double log scale. The pooled dose-response relationship between zinc intake and
      zinc status found that a doubling of zinc intake was associated with an increase
      in serum/plasma zinc status by 3% in pregnant women and by 1% in lactating women.
      These modest associations are likely to reflect the low-moderate zinc
      bioavailability dietary patterns and the widespread use of other micronutrients
      in the populations included in this review, physiologic adjustments of zinc
      homeostasis, insensitivity of serum/plasma zinc as a biomarker of zinc status,
      and wide heterogeneity between study results which reflect real uncertainty in
      the current evidence base. Although this review provides useful information for
      dietary zinc requirements in populations vulnerable to zinc deficiency, it also
      highlights a need for further studies in pregnant and lactating women with
      different dietary patterns in order to provide useful complementary evidence that
      can be utilized when setting zinc recommendations as a basis for nutrition
      policies in Europe.

PMID- 22613061
TI  - Long-term exposure to hexavalent chromium inhibits expression of tumor suppressor
      genes in cultured cells and in mice.
AB  - We have used mouse hepatoma cells in culture to study acute, short-term high-dose
      effects of hexavalent chromium on gene regulation directed by the polycyclic
      aromatic hydrocarbon benzo[a]pyrene (BaP). We find that the mixture engages three
      major signaling pathways: (i) activation of detoxification genes; (ii) induction
      of signal transduction effectors; and (iii) epigenetic modification of chromatin
      marks. Preliminary results in mice exposed to mixtures of low doses of Cr(VI)
      plus BaP indicate that all three pathways are likely to be engaged also in long
      term effects resulting from exposure to environmentally relevant doses of the
      mixture that inhibit the expression of tumor suppressor genes. Given the toxicity
      and carcinogenicity of these mixtures, we expect that a two-way analytical
      approach, from cells in culture to biological effects in vivo and vice versa,
      will provide a better understanding of the molecular mechanisms responsible for
      the biological effects of mixtures. By focusing both the in vivo and the in vitro
      work into long-term, low-dose, environmentally relevant exposures, we expect to
      develop much needed information pertinent to the type of diseases found in human
      populations exposed to mixtures of environmental toxicants.

PMID- 22613062
TI  - Comprehensive analysis of cardiac arrhythmias in telemetered cynomolgus monkeys
      over a 6 month period.
AB  - INTRODUCTION: Cardiac arrhythmia findings can be a challenge to interpret and
      difficult to attribute to background incidence or test article treatment. Thus,
      there is a growing need to better understand arrhythmia incidence in the
      experimental animal models used to assess the cardiovascular safety of new drugs.
      Currently, there is little information on the frequency of spontaneous cardiac
      arrhythmias in the cynomolgus monkey. METHODS: This study evaluated the baseline
      arrhythmia rate in a group (n=19) of non-naive (drug-free) male telemetered
      cynomolgus monkeys at various timepoints over a 6 month period. When sampled,
      data were collected continuously (24 hour bins over a 6 month period) and the ECG
      waveforms analyzed for arrhythmia using a semi-automated approach with pattern
      recognition software. The arrhythmia data were evaluated to detect atrial and
      ventricular patterns, as well as changes associated with circadian rhythm.
      RESULTS: Evaluation of this data showed that cynomolgus monkeys can exhibit
      spontaneous arrhythmias (day cycle; means) of the following types:
      supraventricular premature contraction (SPC, 10.7%); escape beats (EB, 3.8%); and
      sinus node pause (SNP, 2.8%), with others below 2%. From the ventricular
      perspective, ventricular premature beats (VPB, 25.4% (day cycle mean)) were the
      most prevalent. Circadian analysis indicated that some arrhythmias had higher
      incidence during the night cycle: SNP (32.6%); EB (18.5%); atrioventricular block
      (AVB, 2.7%), an indication that the arrhythmia pattern is influenced by the
      diurnal cycle. DISCUSSION: Overall, the data demonstrated that a variety of
      spontaneous arrhythmias occur at low frequency in non-treated animals, and the
      incidence varies between animals, and within the same animal when repeatedly
      sampled. Given the low incidence in normal animals, continuous ECG sampling over
      multiple days is needed to establish an accurate arrhythmia "fingerprint" for
      each animal in dedicated telemetry colonies, which could assist the
      interpretation of arrhythmia findings that may occur in cardiovascular safety
      studies.

PMID- 22613063
TI  - Multiple merger gene genealogies in two species: Monophyly, paraphyly, and
      polyphyly for two examples of Lambda coalescents.
AB  - Probabilities of monophyly, paraphyly, and polyphyly of two-species gene
      genealogies are computed for modest sample sizes and compared for two different
      Lambda coalescent processes. Coalescent processes belonging to the Lambda
      coalescent family admit asynchronous multiple mergers of active ancestral
      lineages. Assigning a timescale to the time of divergence becomes a central issue
      when different populations have different coalescent processes running on
      different timescales. Clade probabilities in single populations are also
      computed, which can be useful for testing for taxonomic distinctiveness of an
      observed set of monophyletic lineages. The coalescence rates of multiple merger
      coalescent processes are functions of coalescent parameters. The effect of
      coalescent parameters on the probabilities studied depends on the coalescent
      process, and if the population is ancestral or derived. The probability of
      reciprocal monophyly tends to be somewhat lower, when associated with a Lambda
      coalescent, under the null hypothesis that two groups come from the same
      population. However, even for fairly recent divergence times, the probability of
      monophyly tends to be higher as a function of the number of generations for
      coalescent processes that admit multiple mergers, and is sensitive to the
      parameter of one of the example processes.

PMID- 22613064
TI  - A concept to transfer a therapeutic splint position into permanent occlusion with
      a customized lingual appliance.
AB  - INTRODUCTION: The role of occlusion concerning temporomandibular disorder is
      still unclear but seems to be the only component of the stomathognathic system
      dentists are able to change morphologically. The aim of the paper is to describe
      the orthodontist's approach for transferring and maintaining a therapeutic splint
      position into permanent occlusion using a fully customized lingual appliance.
      METHODS: Fixed acrylic bite planes on lower molars were used to maintain a
      symptom-free condyle position prior to orthodontic treatment. Silicone
      impressions of the arches including the fixed bite planes were used for the
      Incognito laboratory procedure. Two digital setups were made. One setup
      represents the target occlusion. A second setup including the bite planes was
      used to fabricate an additional set of lower molar brackets. In the leveling
      stage all teeth except the lower molars were settled to maintain the therapeutic
      condyle position. Finally, the fixed bite planes were stepwise removed and molar
      brackets were replaced to establish the permanent occlusion planned with the
      first setup. RESULTS AND DISCUSSION: The advantage of an individual lingual
      appliance consists in the high level of congruence between the fabricated setups
      and the final clinical result. Both the individual scope for design and the
      precision of the appliance were vitally important in the treatment of a patient
      with a functional disorder of the masticatory system.

PMID- 22613065
TI  - Ficts and facts of epinephrine and norepinephrine stability in injectable
      solutions.
AB  - Epinephrine (EPI) and norepinephrine (NE) play an important role in emergency
      medicine and acute treatment of hypotension and shocks in the intensive care
      unit. Injectable solutions can either be provided as proprietary medicinal
      products or as individually prepared dilutions. Due to the chemical structure of
      EPI and NE, the stability of the corresponding solutions is limited. Thus, most
      manufacturers of EPI and NE injectable solutions use sulfites and nitrogen for
      stabilization, Nevertheless, storage conditions such as temperature and light
      have to be considered, but are often neglected in the daily hospital routine. In
      addition, hospital pharmacies prepare EPI and NE solutions and dilute
      commercially available solutions for individual therapy, especially on ICUs.
      Since the influence of dilution and the presence of excipients and other
      preservatives are not systematically explored, we collected published data and
      investigations on stability on the potency of EPI and NE injectable solutions in
      order to deduce storage recommendations for diluted EPI and NE solutions of
      different concentration.

PMID- 22613066
TI  - A theoretical and spectroscopic study of co-amorphous naproxen and indomethacin.
AB  - Co-amorphous drug systems were recently introduced as potential drug delivery
      systems for poorly water soluble drugs in order to overcome problems associated
      with amorphous materials. The improved physical stability and dissolution of
      these systems was attributed to molecular interactions between the co-amorphous
      partners, such as hydrogen bonds. However, molecular level characterization with
      vibrational spectroscopy of even the amorphous drugs alone presents a significant
      challenge. This becomes even more complicated when more than one compound is
      present in the material under investigation. In this study, the co-amorphous drug
      mixture containing naproxen (NAP) and indomethacin (IND) was investigated using
      infrared spectroscopy (IR) and quantum mechanical calculations. The structures of
      both drugs were optimized as monomer, homodimer and heterodimer using density
      functional theory and used for the calculation of IR spectra. Conformational
      analysis confirmed that the optimized structures were suitable for the
      theoretical prediction of the spectra. Vibrational modes from the calculation
      could be matched with experimentally observed spectra for crystalline and
      amorphous NAP and IND, and it could be shown that both drugs exist as homodimers
      in their respective individual amorphous form. With the results from the
      experimental single amorphous drugs and theoretical homodimers, a detailed
      analysis of the experimental co-amorphous and theoretical heterodimer spectra was
      performed and evaluated. It is suggested that NAP and IND exist as heterodimers
      in the co-amorphous mixture when quench cooled together from the melt in a 1:1
      molar ratio. 

PMID- 22613067
TI  - Performance of an artificial neural network for vertical root fracture detection:
      an ex vivo study.
AB  - AIM: To develop an artificial neural network for vertical root fracture
      detection. MATERIALS AND METHODS: A probabilistic neural network design was used
      to clarify whether a tooth root was sound or had a vertical root fracture. Two
      hundred images (50 sound and 150 vertical root fractures) derived from digital
      radiography--used to train and test the artificial neural network--were divided
      into three groups according to the number of training and test data sets:
      80/120,105/95 and 130/70, respectively. Either training or tested data were
      evaluated using grey-scale data per line passing through the root. These data
      were normalized to reduce the grey-scale variance and fed as input data of the
      neural network. The variance of function in recognition data was calculated
      between 0 and 1 to select the best performance of neural network. The performance
      of the neural network was evaluated using a diagnostic test. RESULTS: After
      testing data under several variances of function, we found the highest
      sensitivity (98%), specificity (90.5%) and accuracy (95.7%) occurred in Group
      three, for which the variance of function in recognition data was between 0.025
      and 0.005. CONCLUSIONS: The neural network designed in this study has sufficient
      sensitivity, specificity and accuracy to be a model for vertical root fracture
      detection.

PMID- 22613068
TI  - Temperature and salt effects on settling velocity in granular sludge technology.
AB  - Settling velocity is a crucial parameter in granular sludge technology. In this
      study the effects of temperature and salt concentrations on settling velocities
      of granular sludge particles were evaluated. A two-fold slower settling velocity
      for the same granules where observed when the temperature of water decreases from
      40  degrees C to 5  degrees C. Settling velocities also decreased with increasing
      salt concentrations. Experiments showed that when granules were not pre-incubated
      in a solution with increased salt concentration, they initially floated. The time
      dependent increase in mass and hence in settling speed of a granule due to salt
      diffusion into the granule was dependent on the granule diameter. The time needed
      for full salt equilibrium with the bulk liquid took 1 min for small particles
      from the top of the sludge bed and up to 30 min for big granules from the bottom
      of the sludge bed. These results suggest that temperature and salt concentration
      are important parameters to consider in the design, start-up and operation of
      granular sludge reactors and monitoring of these parameters will aid in a better
      control of the sludge management in anaerobic and aerobic granular sludge
      technology. The observations also give an explanation for previous reports which
      were suggesting that a start-up of granular sludge reactors is more difficult at
      low temperatures.

PMID- 22613069
TI  - Prefrontal EEG correlation during Tower of Hanoi and WCST performance: effect of
      emotional visual stimuli.
AB  - INTRODUCTION: Emotional stimuli elicit changes in the electroencephalographic
      (EEG) activity of several brain structures. Prefrontal cortex is involved in the
      processing of emotional stimuli and executive functions. The correlation analysis
      of EEG provides information about the functional coupling between areas. It is
      reasonable to expect that emotional activation will modify prefrontal coupling
      during the performance of executive tasks such as Tower of Hanoi or Wisconsin
      Card Sorting Test (WCST). AIM: Determine whether the prefrontal EEG correlation
      during the performance of the Tower of Hanoi and WCST is affected by previous
      exposure to videos with sexual or aggressive content. MAIN OUTCOME MEASURES:
      Prefrontal EEG coupling was determined by the Pearson correlation. Valence and
      general arousal were evaluated by the Self-Assessment Manikin Scale and sexual
      arousal with a Sexual Arousal Scale. Computerized versions of the Towers of Hanoi
      and WCST provided data on prefrontal executive functions. METHODS: EEG from the
      left and right prefrontal zones was recorded during the performance of the Tower
      of Hanoi and WCST immediately after the subjects were exposed to one of the
      videos (neutral, aggressive, and erotic). RESULTS: There was no difference
      between videos in the task performance parameters. Only the erotic video produced
      an increased prefrontal coupling in the slow bands (delta and theta) during the
      performance of the Tower of Hanoi, whereas a decreased coupling in the delta,
      theta, and alpha bands was observed during the WCST. CONCLUSIONS: Prefrontal
      coupling was changed after exposure to the erotic video, and it is likely that
      enhanced sexual arousal was the main cause of this change. The correlation
      patterns obtained could be associated with particular cognitive strategies or to
      functional adaptations while being sexually aroused. The results of this study
      may contribute to an understanding of the central nervous mechanisms underlying
      the cognitive effects of sexual arousal.

PMID- 22613070
TI  - Nature and determinants of out-of-pocket health expenditure among older people in
      a rural Indian community.
AB  - BACKGROUND: Increasing out-of-pocket health expenditure among older people
      worsens the inequitable access to essential health services in low and middle
      income countries (LMIC). We investigated various socioeconomic and health factors
      associated with out-of-pocket and catastrophic health expenditures among rural
      older people in India. METHODS: We recruited 1,000 participants aged above 65
      years from Kaniyambadi block, Vellore, India. We assessed their out-of-pocket
      health expenditure, health service utilization, socioeconomic profiles,
      disability, cognition, and health status by standard instruments. We employed
      appropriate multivariate statistics evaluating these determinants. RESULTS: Male
      gender, poor sanitation, diabetes, tuberculosis, malaria, respiratory ailments,
      gastrointestinal diseases, dementia, depression, and disability were associated
      with higher out-of-pocket expenditures. Illiteracy, tuberculosis, diabetes, and
      dementia increased the risk for catastrophic health expenditures, while pension
      schemes protected against it. Income inequalities were associated with inequities
      on education, disease prevalence, and access to safe water, sanitation, and
      nutrition. CONCLUSIONS: Interactions between determinants of out-of-pocket health
      expenditure, economic inequality, and inequities on essential health care
      delivery to older people are complex. We highlight the need for equitable health
      services and policies, focusing on both medical and social determinants.

PMID- 22613071
TI  - Role of the laboratory in monitoring patients receiving dual antiplatelet
      therapy.
AB  - INTRODUCTION: The increasing demand for therapeutic monitoring in patients
      receiving antiplatelet therapy has been paralleled by the development of
      instruments and tests whose clinical usefulness is still under debate. We devised
      a laboratory approach to detect patients with antiplatelet resistance at risk to
      develop thrombotic events. METHODS: One hundred and eighty patients, under
      aspirin and clopidogrel after angioplasty and stent implantation, were studied by
      PFA100((r)) with collagen/epinephrine (CoEPI, cutoff 165s) cartridge and by
      Multiplate((r)) using arachidonic acid (ASPItest, pos < 862AUC), ADP (ADPtest,
      pos < 417AUC), and collagen (COLtest, pos < 607AUC). RESULTS: Only 67 of 173
      patients with ASPI < 862 displayed a prolonged CoEPI and up to 65 patients had
      normal CoEPI despite ASPI < 300. Patients with ASPI < 300 had significantly lower
      COL than patients with ASPI > 300. One hundred and thirty-eight patients
      displaying ADP < 417 had significantly lower COL than those with ADP > 417.
      Association between COL and ADP remained after ASPI stratification: in patients
      with suboptimal (ASPI 300-892) or maximal (ASPI < 300) response to aspirin,
      having ADP < 417 (clopidogrel responsive) increased COL positivity, respectively,
      from 9.5 to 58.8% and from 47.6 to 82.7%. CONCLUSION: A combination of specific
      tests may be useful in identifying higher-risk patients with poor compliance or
      drug resistance who potentially may benefit from therapy change.

PMID- 22613072
TI  - Heptaketides with antiviral activity from three endolichenic fungal strains
      Nigrospora sp., Alternaria sp. and Phialophora sp.
AB  - Two new heptaketides, (+)-(2S,3S,4aS)-altenuene (1a) and (-)-(2S,3S,4aR)
      isoaltenuene (2a), together with six known compounds, (-)-(2R,3R,4aR)-altenuene
      (1b), (+)-(2R,3R,4aS)-isoaltenuene (2b), 5'-methoxy-6-methyl-biphenyl-3,4,3'
      triol (3), alternariol (4), alternariol-9-methyl ether (5), and 4
      hydroxyalternariol-9-methyl ether (6) were isolated from the EtOAc extract of an
      endolichenic fungal strain Nigrospora sphaerica (No.83-1-1-2). Compounds 1a and
      1b were separated from enantiomers 1 by chiral HPLC, and so were 2a and 2b from
      enantiomers 2. Interestingly, 1-6 were also obtained from other two endolichenic
      fungal strains Alternaria alternata (No.58-8-4-1) and Phialophora sp. (No.96-1-8
      1). The structures of 1-6 were elucidated by means of MS, HR-MS, NMR, and X-ray
      diffraction. Furthermore, the absolute configurations of 1a-2b were determined by
      CD experiments and CD calculation. Of these compounds, 4 and 5 showed antiviral
      activity against herpes simplex virus (HSV) in vitro, with IC(50) values of 13.5
      and 21.3 MUM, and with selective index (SI) values of 26.5 and 17.1,
      respectively.

PMID- 22613073
TI  - Chemical constituents of Anacolosa pervilleana and their antiviral activities.
AB  - In an effort to identify novel inhibitors of Chikungunya (CHIKV) and Dengue
      (DENV) virus replication, a systematic study with 820 ethyl acetate extracts of
      Madagascan plants was performed in a virus-cell-based assay for CHIKV and a DENV
      NS5 RNA-dependant RNA polymerase (RdRp) assay. The extract obtained from the
      leaves of Anacolosa pervilleana was selected for its significant activity in both
      assays. One new (E)-tridec-2-en-4-ynedioic acid named anacolosine (1), together
      with three known acetylenic acids, the octadeca-9,11,13-triynoic acid (2), (13E)
      octadec-13-en-9,11-diynoic acid (3), (13E)-octadec-13-en-11-ynoic acid (4), two
      terpenoids, lupenone (5) and beta-amyrone (6), and one cyanogenic glycoside, (S)
      sambunigrin (7) were isolated. Their structures were elucidated by comprehensive
      analyses of NMR spectroscopy and mass spectrometry data. The inhibitory potency
      of these compounds was evaluated on CHIKV, DENV RdRp and West-Nile polymerase
      virus (WNV RdRp). Both terpenoids showed a moderate activity against CHIKV
      (EC(50) 77 and 86 MUM, respectively) and the acetylenic acids produced IC(50)
      values around 3 MUM in the DENV RdRp assay.

PMID- 22613075
TI  - The D-galactose specific lectin of field bean (Dolichos lablab) seed binds sugars
      with extreme negative cooperativity and half-of-the-sites binding.
AB  - The field bean (Dolichos lablab) lectin designated as PPO-haemagglutinin (DLL-II)
      is bifunctional, exhibiting both polyphenol oxidase and haemagglutinating
      activity. The lectin is unusual in that it binds galactose (Gal), lactose (Lac)
      and N-acetylgalactosamine (GalNAc) only in the presence of (NH4)2SO4 and exhibits
      negative cooperativity and half-of-the-sites binding. Circular dichroism,
      isothermal titration calorimetry and fluorescence quenching were used to assess
      the sugar binding in the presence of (NH4)2O4. Comparison of the near-UV CD
      spectra with and without bound sugar revealed ligand induced conformational
      changes. The intrinsic fluorescence quenching data indicate that DLL-II exhibits
      weak binding to Gal in the presence of (NH4)2SO4 with a stoichiometry of one
      bound ligand per dimer. ITC data fitted using a two sets of sites binding model
      presented a similar picture. The K(a)'s for Gal, Lac and GalNAc in the presence
      of (NH4)2SO4 were 0.16+/-0.002, 0.21+/-0.004 and 8.45+/-0.78 (*10-3) M-1
      respectively. The Hill plot for the binding of these sugars to DLL-II was
      curvilinear with a tangent slope <1.0 indicating negative cooperativity. DLL-II
      thus exhibits half-of-the-site binding, an extreme form of negative cooperativity
      in which the second ligand does not bind at all. This is the first report of a
      legume lectin, exhibiting half-of-the-sites binding.

PMID- 22613076
TI  - The carotid body in Sudden Infant Death Syndrome.
AB  - The aim of the present study is to provide a review of cytochemical, clinical and
      experimental data indicating disruption of perinatal carotid body maturation as
      one of the possible mechanisms underlying SIDS pathogenesis. SIDS victims have
      been reported to show alterations in respiratory regulation which may partly be
      ascribed to peripheral arterial chemoreceptors. Carotid body findings in SIDS
      victims, although not entirely confirmed by other authors, have included
      reductions in glomic tissue volume and cytoplamic granules of type I cells,
      changes in cytological composition (higher percentages of progenitor and type II
      cells) and increases in dopamine and noradrenaline contents. Prematurity and
      environmental factors, such as exposure to tobacco smoke, substances of abuse,
      hyperoxia and continuous or intermittent hypoxia, increase the risk of SIDS and
      are known to affect carotid body functional and structural maturation adversely,
      supporting a role for peripheral arterial chemoreceptors in SIDS.

PMID- 22613074
TI  - Enhanced susceptibility to lipopolysaccharide-induced arthritis and endotoxin
      shock in interleukin-32 alpha transgenic mice through induction of tumor necrosis
      factor alpha.
AB  - INTRODUCTION: The present study assessed the potential functions of interleukin
      (IL)-32alpha on inflammatory arthritis and endotoxin shock models using IL
      32alpha transgenic (Tg) mice. The potential signaling pathway for the IL-32-tumor
      necrosis factor (TNF)alpha axis was analyzed in vitro. METHODS: IL-32alpha Tg
      mice were generated under control of a ubiquitous promoter. Two disease models
      were used to examine in vivo effects of overexpressed IL-32alpha: Toll-like
      receptor (TLR) ligand-induced arthritis developed using a single injection of
      lipopolysaccharide (LPS) or zymosan into the knee joints; and endotoxin shock
      induced with intraperitoneal injection of LPS and D-galactosamine. TNFalpha
      antagonist etanercept was administered simultaneously with LPS in some mice.
      Using RAW264.7 cells, in vitro effects of exogenous IL-32alpha on TNFalpha, IL-6
      or macrophage inflammatory protein 2 (MIP-2) production were assessed with or
      without inhibitors for nuclear factor kappa B (NFkappaB) or mitogen-activated
      protein kinase (MAPK). RESULTS: Single injection of LPS, but not zymosan,
      resulted in development of severe synovitis with substantial articular cartilage
      degradation in knees of the Tg mice. The expression of TNFalpha mRNA in inflamed
      synovia was highly upregulated in the LPS-injected Tg mice. Moreover, the Tg mice
      were more susceptive to endotoxin-induced lethality than the wild-type control
      mice 48 hours after LPS challenge; but blockade of TNFalpha by etanercept
      protected from endotoxin lethality. In cultured bone marrow cells derived from
      the Tg mice, overexpressed IL-32alpha accelerated production of TNFalpha upon
      stimulation with LPS. Of note, exogenously added IL-32alpha alone stimulated
      RAW264.7 cells to express TNFalpha, IL-6, and MIP-2 mRNAs. Particularly, IL
      32alpha -induced TNFalpha, but not IL-6 or MIP-2, was inhibited by
      dehydroxymethylepoxyquinomicin (DHMEQ) and U0126, which are specific inhibitors
      of nuclear factor kappa B (NFkappaB) and extracellular signal regulated kinase1/2
      (ERK1/2), respectively. CONCLUSIONS: These results show that IL-32alpha
      contributed to the development of inflammatory arthritis and endotoxin lethality.
      Stimulation of TLR signaling with LPS appeared indispensable for activating the
      IL-32alpha-TNFalpha axis in vivo. However, IL-32alpha alone induced TNFalpha
      production in RAW264.7 cells through phosphorylation of inhibitor kappa B
      (IkappaB) and ERK1/2 MAPK. Further studies on the potential involvement of IL
      32alpha-TNFalpha axis will be beneficial in better understanding the pathology of
      autoimmune-related arthritis and infectious immunity.

PMID- 22613077
TI  - The effect of alveolar dead space on the measurement of end-expiratory lung
      volume by modified nitrogen wash-out/wash-in in lavage-induced lung injury.
AB  - BACKGROUND: The accuracy of end-expiratory lung volume measurement by the
      modified nitrogen wash-out/wash-in method (EELV-N(2)) depends on the precise
      determination of carbon dioxide elimination (V(CO(2))), which is affected by
      alveolar dead space (V(D-alv)). The purpose of this study was to investigate the
      influence of V(D-alv) on EELV-N(2). METHODS: Six piglets with lavage-induced
      acute lung injury were mechanically ventilated in a decremental PEEP trial that
      was reduced from 20 to 4 cm H(2)O in steps of 4 cm H(2)O every 10 min. EELV was
      measured by the modified EELV-N(2) method and computed tomography scan (EELV-CT),
      volumetric capnography, blood gas measurements, and hemodynamic data were
      recorded at each PEEP level. The data were divided into higher and lower PEEP
      groups. RESULTS: During the decremental PEEP trial, EELV-N(2) exhibited a high
      correlation (r(2) = 0.86, P < .001) with EELV-CT, with a bias of -48.6 +/- 150.7
      mL (1 +/- 18%). In the higher PEEP group, EELV-N(2) was not correlated with EELV
      CT, with a bias of -168.1 +/- 171.5 mL (-14 +/- 14%). However, in the lower PEEP
      group, EELV-N(2) exhibited a high correlation (r(2) = 0.86, P < .001) with EELV
      CT, with a bias of 11.2 +/- 97.2 mL (6 +/- 17%). The measurement bias was
      negatively correlated with V(D-alv) (r(2) = 0.44, P = .04) and V(CO(2)) (r(2) =
      0.47, P = .03) in the higher PEEP group. CONCLUSIONS: In this surfactant-depleted
      model, EELV measurement by the modified EELV-N(2) method reveals a systematic
      underestimation at high PEEP levels that is partly due to an increase in V(D
      alv).

PMID- 22613078
TI  - Meat quality and cooking attributes of thawed pork with different low field NMR
      T(21).
AB  - A relationship of low field NMR T(2) components to meat quality and cooking
      attributes of pork was investigated. Longissimus muscle was removed from 23 pig
      carcasses at 24h postmortem for meat quality measurements and cooking test.
      Frozen samples were classified into three groups by LF-NMR T(21) of thawed
      samples: A (<40ms), B (40-44ms) and C (>44ms). There were significant differences
      (P<0.05) in pH, lightness (L* value) and pressing loss among the three groups.
      Cooking time to attain 70 degrees C was slightly lower in group C than the other
      groups. Shear force value of cooked samples was not affected by T(21). The
      component T(21) correlated (P<0.05) with L* value, muscle pH and pressing loss,
      while L* value correlated (P<0.05) with thawing loss and muscle pH. Therefore,
      combined LF-NMR and color measurements could be a good way to differentiate water
      holding capacity of pork.

PMID- 22613079
TI  - Pharmacokinetic behavior and efficiency of acetylcholinesterase inhibition in rat
      brain after intranasal administration of galanthamine hydrobromide loaded
      flexible liposomes.
AB  - Galanthamine hydrobromide (GH) has been approved for symptomatic treatment of
      Alzheimer's disease (AD) and vascular dementia. Hence, the effects of intranasal
      administration of GH loaded flexible liposomes have been investigated for the
      first time on the efficiency of acetylcholinesterase inhibition, as well as the
      pharmacokinetic behavior of GH in rat brain. The GH loaded flexible liposomes
      were characterized for shape, entrapment capacity, size distribution and zeta
      potential by transmission electron microscopy (TEM), ultracentrifugation and
      dynamic light scattering (DLS), respectively. The inhibition of
      acetylcholinesterase was investigated using rat brain homogenates as an enzyme
      resource and microdialysis was used to determine the pharmacokinetic behavior of
      GH in rats brain. The rat pheochromocytoma PC-12 cell line was used to evaluate
      the cytotoxicity of GH loaded flexible liposomes. The results revealed that: (i)
      the efficiency of acetylcholinesterase inhibition of GH was greatly enhanced by
      intranasal administration compared with oral administration, especially GH loaded
      in flexible liposomes; (ii) the C(max) and AUC(0->10) for intranasal
      administration of GH loaded flexible liposomes were 3.52 and 3.36 times higher
      than those of orally administered GH, moreover, the T(max) was greatly shortened
      from 1.5h for oral administration to 0.75h for intranasal administration of GH
      loaded flexible liposomes; and (iii) PC-12 cells viability tests showed that the
      flexible liposome carrier is not toxic to the cultured cells and the cytotoxicity
      of GH to cells was clearly decreased by loading in flexible liposomes. These
      results indicate that intranasal administration of GH loaded flexible liposomes
      could readily transport GH into brain tissues, suggesting some promise for this
      approach in successful brain-drug targeting in AD treatment.

PMID- 22613080
TI  - Phenotypic and allelic profile of ABO and Rhesus D blood group system among blood
      donor in Antananarivo.
AB  - This study assessed the phenotypic and allelic profiles of ABO and Rhesus D blood
      group system among first time blood donors at the National Centre of Blood Supply
      of Antananarivo. We collected through this retrospective study all data
      registered during 7 years of practice (from 2003 to 2009). Age and sex were
      analysed with the result of ABO and RhD screening. They were tested both with
      Beth Vincent and Simonin tests which were performed in a plate, by using
      commercial monoclonal antibody (Diaclone((r)) et Eryclone((r))), and home-made
      red cells tests. The Rh D was performed with the same commercial kits. The
      frequencies of alleles were calculated by using Bernstein method. Data about
      45,857 donors were obtained. A male predominance (80.46%) was found and most of
      our donors were aged <40 (74.92%). 98.90% of the donors were Rh D positive.
      Phenotypic distribution of each ABO antigen was, respectively, 22.61, 29.66, 6.13
      and 41.60% for A, B, AB and O antigen. Allelic frequencies of A, B and O were
      0.1559, 0.1987 and 0.6454. These results confirmed the fact that Madagascan
      population had admixed ethnic origin.

PMID- 22613081
TI  - Traumatic dental injuries at a German university clinic 2004-2008.
AB  - AIM: This study was designed to analyse the distribution and treatment management
      of patients who presented at a German university dental emergency department for
      trauma in a 5-year period. MATERIALS/METHODS: Clinical and radiographical
      baseline data and recall of patients presenting from 2004 to 2008 for dental
      trauma were evaluated with regard to age, gender, type of injury and treatment
      strategies. In addition, trauma management as performed was compared with the
      guidelines of the International Association of Dental Traumatology (IADT).
      RESULTS: A total of 361 teeth in 219 patients from 1 to 68 years were treated
      with 1.7 injured teeth per incident and patient. Over 75% of the patients were <
      14 years. In 23% of all incidents, primary teeth were affected with a male-to
      female ratio of 2.1:1. Luxation injuries were predominant in the deciduous
      dentition. The domestic environment was the most common trauma location (44%),
      followed by nursery schools (36%) and outdoors during recreational activities
      (20%) mainly caused by falls (72%). In 76% of all dental injuries, permanent
      teeth were involved; 65% of patients were men; and 35%, women (1.8:1). With
      permanent teeth, enamel-dentine fracture without pulp involvement was most
      common. Falls (38%), accidental contacts (21%) and sports accidents (18%) caused
      the most injuries. The majority of teeth were treated in concordance with the
      guidelines (89%). CONCLUSIONS: The distribution of traumatic injuries is similar
      to other national and international data with regard to gender, age and in
      relation to injury type, location and causes. International and national
      healthcare associations and teachers in under- and postgraduate education should
      put effort on increasing the awareness of the guidelines.

PMID- 22613082
TI  - Preferences for end-of-life treatment: concordance between older adults with
      dementia or mild cognitive impairment and their spouses.
AB  - BACKGROUND: There is considerable debate about the ability of proxies to
      adequately reflect patients' preferences regarding end-of-life care, when
      patients are no longer capable of stating their preferences. This study evaluated
      concordance in end-of-life preferences between patients with mild cognitive
      impairment (MCI) or dementia and their spouses. METHODS: A cross-sectional sample
      of 106 respondents (53 couples) was recruited in two psychogeriatric clinics.
      Bivariate analyses were conducted to evaluate the degree of agreement between the
      patients' preferences and those of their spouses. RESULTS: Patients were more
      likely to opt for more treatment than their spouses. Moderate agreement between
      patients and spouses was evident for preferences regarding end-of-life decisions
      for the patients. There was little concordance between the wishes of spouses
      regarding their own preferences and what they wanted for the patient or what the
      patient wanted. When incorrectly predicting patients' preferences, spouses were
      more likely to ask for treatment. CONCLUSIONS: Our results show that regarding
      end-of-life preferences for patients, there is moderate agreement between
      patients and their spouses, but limited evidence for projection of spouses'
      preferences on patients (i.e. spouse making a prediction based on own wishes).
      Potential differences in end-of-life preferences between older adults with MCI or
      mild dementia and their caregivers should be taken into consideration in the
      preparation of advance care planning.

PMID- 22613083
TI  - Brain-derived neurotrophic factor from microglia: a molecular substrate for
      neuropathic pain.
AB  - One of the most significant advances in pain research is the realization that
      neurons are not the only cell type involved in the etiology of chronic pain. This
      realization has caused a radical shift from the previous dogma that neuronal
      dysfunction alone accounts for pain pathologies to the current framework of
      thinking that takes into account all cell types within the central nervous system
      (CNS). This shift in thinking stems from growing evidence that glia can modulate
      the function and directly shape the cellular architecture of nociceptive networks
      in the CNS. Microglia, in particular, are increasingly recognized as active
      principal players that respond to changes in physiological homeostasis by
      extending their processes toward the site of neural damage, and by releasing
      specific factors that have profound consequences on neuronal function and that
      contribute to CNS pathologies caused by disease or injury. A key molecule that
      modulates microglia activity is ATP, an endogenous ligand of the P2 receptor
      family. Microglia expresses several P2 receptor subtypes, and of these the P2X4
      receptor subtype has emerged as a core microglia-neuron signaling pathway:
      activation of this receptor drives the release of brain-derived neurotrophic
      factor (BDNF), a cellular substrate that causes disinhibition of pain
      transmitting spinal lamina I neurons. Converging evidence points to BDNF from
      spinal microglia as being a critical microglia-neuron signaling molecule that
      gates aberrant nociceptive processing in the spinal cord. The present review
      highlights recent advances in our understanding of P2X4 receptor-mediated
      signaling and regulation of BDNF in microglia, as well as the implications for
      microglia-neuron interactions in the pathobiology of neuropathic pain.

PMID- 22613085
TI  - HAltORF: a database of predicted out-of-frame alternative open reading frames in
      human.
AB  - Human alternative open reading frames (HAltORF) is a publicly available and
      searchable online database referencing putative products of out-of-frame
      alternative translation initiation (ATI) in human mRNAs. Out-of-frame ATI is a
      process by which a single mRNA encodes independent proteins, when distinct
      initiation codons located in different reading frames are recognized by a
      ribosome to initiate translation. This mechanism is largely used in viruses to
      increase the coding potential of small viral genomes. There is increasing
      evidence that out-of-frame ATI is also used in eukaryotes, including human, and
      may contribute to the diversity of the human proteome. HAltORF is the first web
      based searchable database that allows thorough investigation in the human
      transcriptome of out-of-frame alternative open reading frames with a start codon
      located in a strong Kozak context, and are thus the more likely to be expressed.
      It is also the first large scale study on the human transcriptome to successfully
      predict the expression of out-of-frame ATI protein products that were previously
      discovered experimentally. HAltORF will be a useful tool for the identification
      of human genes with multiple coding sequences, and will help to better define and
      understand the complexity of the human proteome. Database URL:
      http://haltorf.roucoulab.com/.

PMID- 22613084
TI  - Structure-activity and immunochemical data provide evidence of developmental- and
      tissue-specific myosuppressin signaling.
AB  - Myosuppressin peptides dramatically diminish contractions of the gut and heart.
      Thus, delineating mechanisms involved in myosuppressin signaling may provide
      insight into peptidergic control of muscle contractility. Drosophila
      myosuppressin (DMS, TDVDHVFLRFamide) structure-activity relationship (SAR) was
      investigated to identify an antagonist and explore signaling. Alanyl-substituted,
      N-terminal truncated, and modified amino acid analogs identified residues and
      peptide length required for activity. Immunochemistry independently provided
      insight into myosuppressin mechanisms. DMS decreased gut motility and cardiac
      contractility dose dependently; the different effective concentrations at half
      maximal-response were indicative of tissue-specific mechanisms. Replacement of
      aspartic acid 2 (D2) generated an analog with different developmental- and tissue
      specific effects; [A2] DMS mimicked DMS in adult gut (100% inhibition), yet
      decreased larval gut contractions by only 32% with increased potency in pupal
      heart (126% inhibition). The DMS active core differed across development and in
      tissues; adult (DHVFLRFamide) and larval gut (TDVDHVFLRFamide), and adult
      (VFLRFamide) and pupal heart (VFLRFamide). Substitution of D2 and D4 with a
      modified amino acid, p-benzoyl-phenylalanine, produced developmental- and tissue
      specific antagonists. In the presence of protease inhibitors, DMS and VFLRFamide
      were more effective in adult gut, but lower or unchanged in pupal heart compared
      to peptide or analog alone, respectively. DMS-specific antisera stained neurons
      that innervated the gut or heart. This study describes novel antagonists and data
      to identify developmental- and tissue-specific mechanisms underlying the
      pleotropic effects of myosuppressin in muscle physiology.

PMID- 22613086
TI  - Effects of temperature on mortality in Chiang Mai city, Thailand: a time series
      study.
AB  - BACKGROUND: The association between temperature and mortality has been examined
      mainly in North America and Europe. However, less evidence is available in
      developing countries, especially in Thailand. In this study, we examined the
      relationship between temperature and mortality in Chiang Mai city, Thailand,
      during 1999-2008. METHOD: A time series model was used to examine the effects of
      temperature on cause-specific mortality (non-external, cardiopulmonary,
      cardiovascular, and respiratory) and age-specific non-external mortality (<=64,
      65-74, 75-84, and > =85 years), while controlling for relative humidity, air
      pollution, day of the week, season and long-term trend. We used a distributed lag
      non-linear model to examine the delayed effects of temperature on mortality up to
      21 days. RESULTS: We found non-linear effects of temperature on all mortality
      types and age groups. Both hot and cold temperatures resulted in immediate
      increase in all mortality types and age groups. Generally, the hot effects on all
      mortality types and age groups were short-term, while the cold effects lasted
      longer. The relative risk of non-external mortality associated with cold
      temperature (19.35 degrees C, 1st percentile of temperature) relative to 24.7
      degrees C (25th percentile of temperature) was 1.29 (95% confidence interval
      (CI): 1.16, 1.44) for lags 0-21. The relative risk of non-external mortality
      associated with high temperature (31.7 degrees C, 99th percentile of temperature)
      relative to 28 degrees C (75th percentile of temperature) was 1.11 (95% CI: 1.00,
      1.24) for lags 0-21. CONCLUSION: This study indicates that exposure to both hot
      and cold temperatures were related to increased mortality. Both cold and hot
      effects occurred immediately but cold effects lasted longer than hot effects.
      This study provides useful data for policy makers to better prepare local
      responses to manage the impact of hot and cold temperatures on population health.

PMID- 22613087
TI  - Induction of pulmonary fibrosis by cerium oxide nanoparticles.
AB  - Cerium compounds have been used as a diesel engine catalyst to lower the mass of
      diesel exhaust particles, but are emitted as cerium oxide (CeO(2)) nanoparticles
      in the diesel exhaust. In a previous study, we have demonstrated a wide range of
      CeO(2)-induced lung responses including sustained pulmonary inflammation and
      cellular signaling that could lead to pulmonary fibrosis. In this study, we
      investigated the fibrogenic responses induced by CeO(2) in a rat model at various
      time points up to 84 days post-exposure. Male Sprague Dawley rats were exposed to
      CeO(2) by a single intratracheal instillation. Alveolar macrophages (AM) were
      isolated by bronchial alveolar lavage (BAL). AM-mediated cellular responses,
      osteopontin (OPN) and transform growth factor (TGF)-beta1 in the fibrotic process
      were investigated. The results showed that CeO(2) exposure significantly
      increased fibrotic cytokine TGF-beta1 and OPN production by AM above controls.
      The collagen degradation enzymes, matrix metalloproteinase (MMP)-2 and -9 and the
      tissue inhibitor of MMP were markedly increased in the BAL fluid at 1 day- and
      subsequently declined at 28 days after exposure, but remained much higher than
      the controls. CeO(2) induced elevated phospholipids in BAL fluid and increased
      hydroxyproline content in lung tissue in a dose- and time-dependent manner.
      Immunohistochemical analysis showed MMP-2, MMP-9 and MMP-10 expressions in
      fibrotic regions. Morphological analysis noted increased collagen fibers in the
      lungs exposed to a single dose of 3.5mg/kg CeO(2) and euthanized at 28 days post
      exposure. Collectively, our studies show that CeO(2) induced fibrotic lung injury
      in rats, suggesting it may cause potential health effects.

PMID- 22613088
TI  - A short history of the discovery of the erythrocyte sedimentation rate.

PMID- 22613089
TI  - Exploring the impact of climate on human longevity.
AB  - The purpose of this study was to examine the impact of physical geographic
      factors and climate conditions on human longevity. The centenarian rate (CR) in
      2005 was computed for Japan's 47 prefectures, whose geography and climate vary
      greatly. Several pathways, such as excess winter mortality, land use and
      agricultural production, possibly linking physical and climate factors with
      extreme longevity, were explored. The probability of becoming a centenarian
      varies significantly among the Japanese prefectures. In particular, the
      computation of CR(70) demonstrated that the actual probability for individuals 70
      years old in 1975 of becoming centenarians in 2005 was 3 times higher, on
      average, in Okinawa, both for males and females, than in Japan as a whole. About
      three quarters of the variance in CR(70) for females and half for males is
      explained by the physical environment and land use, even when variations in the
      level of socio-economic status between prefectures are controlled. Our analysis
      highlighted two features which might have played an important role in the
      longevity observed in Okinawa. First, there is virtually no winter in Okinawa.
      For instance, the mean winter temperature observed in 2005 was 17.2 degrees C.
      Second, today, there is almost no rice production in Okinawa compared to other
      parts of Japan. In the past, however, production was higher in Okinawa. If we
      consider that long term effects of harsh winters can contribute to the mortality
      differential in old age and if we consider that food availability in the first
      part of the 20th century was mainly dependent on local production, early 20th
      century birth cohorts in Okinawa clearly had different experiences in terms of
      winter conditions and in terms of food availability compared to their
      counterparts in other parts of Japan. This work confirms the impact of climate
      conditions on human longevity, but it fails to demonstrate a strong association
      between longevity and mountainous regions and/or air quality.

PMID- 22613090
TI  - T cell tolerance and immunity to commensal bacteria.
AB  - The commensal bacteria normally resident in the gastrointestinal tract represent
      an enormous pool of foreign antigen within the body. Although mechanical barriers
      limit entry of bacteria into the host, recent data suggest that T cells routinely
      interact with commensal bacteria using both antigen-specific and non-specific
      receptors. Depending on the bacterial species, either regulatory or effector T
      cell responses can be generated. For example, segmented filamentous bacteria
      (SFB) favor effector Th17 responses whereas Bacteroides fragilis and certain
      Clostridium species favor Foxp3+ regulatory T (Treg) cell responses. Thus, in
      contrast with the notion that only tolerogenic responses are required to self,
      gut homeostasis may require both tolerance and immunity to various constituents
      of the commensal microbiota.

PMID- 22613091
TI  - Immunity to fungi.
AB  - The global increase in fungal disease burden, the emergence of novel pathogenic
      fungi, and the lack of fungal vaccines have focused intense interest in
      elucidating immune defense mechanisms against fungi. Recent studies in animal
      models and in humans identify an integrated role for C-type lectin and Toll-like
      receptor signaling in activating innate and adaptive responses that control
      medically relevant fungi. Beyond the critical role of phagocytes in host defense,
      the generation and balance of specific T helper subsets contributes to
      sterilizing immunity. These advances form a basis for the development of fungal
      vaccines and immune-based therapeutic adjuncts.

PMID- 22613092
TI  - Protection versus pathology in tuberculosis: recent insights.
AB  - Recent studies have revisited the roles of prime players in the immune response
      to tuberculosis (TB) and have highlighted novel functions of these players.
      Specifically, immunoregulatory mechanisms mediated by IFNgamma have been
      delineated as well as a novel role for neutrophils in promoting antigen
      presentation. New insights into the interaction between the bacterium and
      phagocyte indicate that the bacterium actively promotes phagocyte necrosis rather
      than apoptosis and that this impacts generation of the acquired response. There
      are also many new examples of how the phagocyte responds to the bacteria and how
      it mediates control. The phenotype of protective T cells is also being re
      examined. These developments provide promise for improved vaccine design and
      highlight the complexity of this disease.

PMID- 22613093
TI  - Vaccination against Feline Panleukopenia: implications from a field study in
      kittens.
AB  - BACKGROUND: Feline Panleukopenia (FPL) is a serious disease of cats that can be
      prevented by vaccination. Kittens are routinely vaccinated repeatedly during
      their first months of life. By this time maternally derived antibodies (MDA) can
      interfere with vaccination and inhibit the development of active immunity. The
      efficacy of primary vaccination under field conditions was questioned by frequent
      reports to the Paul-Ehrlich-Institut on outbreaks of FPL in vaccinated breeding
      catteries. We therefore initiated a field study to investigate the development of
      immunity in kittens during primary vaccination against FPL.64 kittens from 16
      litters were vaccinated against FPL at the age of 8, 12 and 16 weeks using three
      commercial polyvalent vaccines. Blood samples were taken before each vaccination
      and at the age of 20 weeks. Sera were tested for antibodies against Feline
      Panleukopenia Virus (FPV) by hemagglutination inhibition test and serum
      neutralisation assay in two independent diagnostic laboratories. RESULTS: There
      was a good correlation between the results obtained in different laboratories and
      with different methods. Despite triple vaccination 36.7% of the kittens did not
      seroconvert. Even very low titres of MDA apparently inhibited the development of
      active immunity. The majority of kittens displayed significant titres of MDA at 8
      and 12 weeks of age; in some animals MDA were still detected at 20 weeks of age.
      Interestingly, the vaccines tested differed significantly in their ability to
      overcome low levels of maternal immunity. CONCLUSIONS: In the given situation it
      is recommended to quantify antibodies against FPV in the serum of the queen or
      kittens before primary vaccination of kittens. The beginning of primary
      vaccination should be delayed until MDA titres have declined. Unprotected kittens
      that have been identified serologically should be revaccinated.

PMID- 22613094
TI  - Neuroplasticity: an appreciation from synapse to system.
AB  - OBJECTIVE: To integrate our functional knowledge in neurorehabilitation with a
      greater understanding of commonly held theories and current research in
      neuroplasticity. DESIGN: Literature review. SETTING: Not applicable.
      PARTICIPANTS: Animal and human research. INTERVENTIONS: Interventions specific to
      application in humans: constraint-induced movement therapy, transcranial magnetic
      stimulation, and transcranial direct current stimulation. MAIN OUTCOME MEASURES:
      Cortical excitability, blood oxygen level-dependent signal, and functional
      outcomes. RESULTS: There is increasing evidence elucidating the cellular and
      molecular mechanisms of plasticity of the nervous system including growth,
      modification, degradation, and even death of neurons. Some of these mechanisms
      directly correlate with therapy-induced behavioral changes, and all provide an
      understanding of the response of the nervous system to altered inputs. The
      understanding of neural correlates of behavior can then form the foundation for
      more productive, comprehensive interventions. CONCLUSIONS: The focus of recent
      research surrounds translational projects aimed at enhancing clinical outcomes.
      Knowledge of mechanisms underlying this adaptability is the foundation for our
      treatments, diagnoses, and prognoses. The increasing understanding of the
      mechanisms underlying neuroplasticity can guide, direct, and focus the practice
      of current and future therapies to greater efficacy and better functional
      outcomes in clinical rehabilitation.

PMID- 22613096
TI  - Structural and functional characterization of recombinant medaka fish alpha
      amylase expressed in yeast Pichia pastoris.
AB  - The medaka fish alpha-amylase was expressed and purified. The expression systems
      were constructed using methylotrophic yeast Pichia pastoris, and the recombinant
      proteins were secreted into the culture medium. Purified recombinant alpha
      amylase exhibited starch hydrolysis activity. The optimal pH, denaturation
      temperature, and K(M) and V(max) values were determined; chloride ions were
      essential for enzyme activity. The purified protein was also crystallized and
      examined by X-ray crystallography. The structure has the (alpha/beta)(8) barrel
      fold, as do other known alpha-amylases, and the overall structure is very similar
      to the structure of vertebrate (human and pig) alpha-amylases. A novel expression
      plasmid was developed. Using this plasmid, high-throughput construction of an
      expression system by homologous recombination in P. pastoris cells, previously
      reported for membrane proteins, was successfully applied to the secretory
      protein.

PMID- 22613097
TI  - Can albuterol be blamed for lactic acidosis?

PMID- 22613095
TI  - Targeting triple-negative breast cancer cells with the histone deacetylase
      inhibitor panobinostat.
AB  - INTRODUCTION: Of the more than one million global cases of breast cancer
      diagnosed each year, approximately fifteen percent are characterized as triple
      negative, lacking the estrogen, progesterone, and Her2/neu receptors. Lack of
      effective therapies, younger age at onset, and early metastatic spread have
      contributed to the poor prognoses and outcomes associated with these
      malignancies. Here, we investigate the ability of the histone deacetylase
      inhibitor panobinostat (LBH589) to selectively target triple-negative breast
      cancer (TNBC) cell proliferation and survival in vitro and tumorigenesis in vivo.
      METHODS: TNBC cell lines MDA-MB-157, MDA-MB-231, MDA-MB-468, and BT-549 were
      treated with nanomolar (nM) quantities of panobinostat. Relevant histone
      acetylation was verified by flow cytometry and immunofluorescent imaging. Assays
      for trypan blue viability, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) proliferation, and DNA fragmentation were used to evaluate overall
      cellular toxicity. Changes in cell cycle progression were assessed with propidium
      iodide flow cytometry. Additionally, qPCR arrays were used to probe MDA-MB-231
      cells for panobinostat-induced changes in cancer biomarkers and signaling
      pathways. Orthotopic MDA-MB-231 and BT-549 mouse xenograft models were used to
      assess the effects of panobinostat on tumorigenesis. Lastly, flow cytometry,
      ELISA, and immunohistochemical staining were applied to detect changes in
      cadherin-1, E-cadherin (CDH1) protein expression and the results paired with
      confocal microscopy in order to examine changes in cell morphology. RESULTS:
      Panobinostat treatment increased histone acetylation, decreased cell
      proliferation and survival, and blocked cell cycle progression at G2/M with a
      concurrent decrease in S phase in all TNBC cell lines. Treatment also resulted in
      apoptosis induction at 24 hours in all lines except the MDA-MB-468 cell line. MDA
      MB-231 and BT-549 tumor formation was significantly inhibited by panobinostat (10
      mg/kg/day) in mice. Additionally, panobinostat up-regulated CDH1 protein in vitro
      and in vivo and induced cell morphology changes in MDA-MB-231 cells consistent
      with reversal of the mesenchymal phenotype. CONCLUSIONS: This study revealed that
      panobinostat is overtly toxic to TNBC cells in vitro and decreases tumorigenesis
      in vivo. Additionally, treatment up-regulated anti-proliferative, tumor
      suppressor, and epithelial marker genes in MDA-MB-231 cells and initiated a
      partial reversal of the epithelial-to-mesenchymal transition. Our results
      demonstrate a potential therapeutic role of panobinostat in targeting aggressive
      triple-negative breast cancer cell types.

PMID- 22613099
TI  - [A pilot trial on the treatment of gastroesophageal reflux-related cough in
      infants].
AB  - OBJECTIVE: Diagnosing asthma in infancy is largely made on the basis of the
      symptoms of cough and wheezing. A similar presentation can be seen in
      neurologically normal infants with excessive gastroesophageal reflux (GER). There
      are no randomized placebo controlled studies in infants using proton pump
      inhibitors (PPI) alone or in addition to prokinetic agents. The primary objective
      was to confirm the presence of excessive GER in a population of infants that also
      had respiratory symptoms suggestive of asthma. Second, in a randomized placebo
      controlled fashion, we determined whether treatment of GER with bethanacol and
      omeprazole could improve these respiratory symptoms. METHODS: Infants (n=22) with
      a history of chronic cough and wheeze were enrolled, if they had evidence of GER
      by history and an abnormal pH probe or gastric emptying scan. Infants were
      randomly allocated to four treatment groups: placebo/placebo (PP), omeprazole
      plus bethanacol (OB), omeprazole/placebo (OP), bethanacol/placebo (BP).
      Evaluations by clinic questionnaire and exam, home diary, and pH probe data were
      done before, after study-medication and after open label of OB. RESULTS: Nineteen
      children were studied. PP did not affect GER or respiratory symptoms, and did not
      decrease GER measured by pH probe. In contrast, OB decreased GER as measured by
      pH probe indices and parental assessment. In association, OB significantly
      decreased daytime coughing and improved respiratory scores. No adverse effects
      were reported. CONCLUSIONS: In infants with a clinical presentation suggestive of
      chronic GER-related cough, the use of omeprazole and bethanacol appears to be
      viable therapeutic option.

PMID- 22613100
TI  - [Factors influencing short-term prognosis of tuberculous meningitis in children].
AB  - OBJECTIVE: To study the factors influencing short-term prognosis of tuberculous
      meningitis (TBM) in children. METHODS: The clinical data of 137 hospitalized
      children with TBM between January 2007 and February 2011 were retrospectively
      reviewed. A total of 30 potential factors influencing short-term prognosis of TBM
      were evaluated by univariate analysis and multivariate logistic regression
      analysis. RESULTS: Clinical staging showed that of the 137 children 21 cases
      (15.3%) were in the early stage, 67 cases (48.9%) in the medium stage and 49
      cases (35.8%) in the late stage of TBM. The univariate analysis revealed 8
      factors associated with a poor short-term prognosis: clinical stage of TBM
      (late), coma, positive Babinski signs, cranial nerve involvements, paralysis,
      seizures, obvious abnormalities in brain computed tomography (CT) or magnetic
      resonance imaging (MRI) and elevated protein concentrations in cerebrospinal
      fluid (CSF). Factors associated with a favourable short-term prognosis for TBM
      included glucocorticoid steroids therapy, positive reaction of PPD skin test and
      an increased length of stay in hospital. Multivariate logistic analysis revealed
      two independent risk factors for a poor short-term prognosis: clinical stage of
      TBM (late) (OR: 11.168, 95%CI: 3.521-35.426) and positive signs of meningeal
      irritation (OR: 4.275, 95%CI: 1.043-17.521). An increased length of stay in
      hospital was shown as a favorable factor (OR: 0.893, 95%CI: 0.825-0.968).
      CONCLUSIONS: Late-stage TBM and positive signs of meningeal irritation suggest a
      poor prognosis, while an appropriately longer length of stay in hospital may
      contribute to a favorable short-term prognosis for children with TBM.

PMID- 22613098
TI  - Novel cruzain inhibitors for the treatment of Chagas' disease.
AB  - The protozoan parasite Trypanosoma cruzi, the etiological agent of Chagas'
      disease, affects millions of individuals and continues to be an important global
      health concern. The poor efficacy and unfavorable side effects of current
      treatments necessitate novel therapeutics. Cruzain, the major cysteine protease
      of T. cruzi, is one potential novel target. Recent advances in a class of vinyl
      sulfone inhibitors are encouraging; however, as most potential therapeutics fail
      in clinical trials and both disease progression and resistance call for
      combination therapy with several drugs, the identification of additional classes
      of inhibitory molecules is essential. Using an exhaustive virtual-screening and
      experimental validation approach, we identify several additional small-molecule
      cruzain inhibitors. Further optimization of these chemical scaffolds could lead
      to the development of novel drugs useful in the treatment of Chagas' disease.

PMID- 22613101
TI  - [Clinical significance of determining urinary podocalyxin level in children with
      primary nephrotic syndrome].
AB  - OBJECTIVE: To study the clinical significance of urinary podocyte marker protein
      podocalyxin (PCX) in the diagnosis of primary nephrotic syndrome (PNS) in
      children and the evaluation of disease severity. METHODS: PCX levels in the first
      morning urine were measured by turbidimetric immunoassay (TIA) in 175 children,
      including 53 children with acute PNS [36 cases of simple nephrotic syndrome (NS)
      and 17 cases of nephritic NS], 56 children with PNS in the remission stage
      (relapsed: 42 cases) and 66 healthy children (control group). Twenty-four hour
      urinary protein was measured in the 53 children with acute PNS. The optimal
      operating points for the diagnosis of acute PNS and nephritic NS were determined
      using the receiver-operating characteristic curve (ROC curve). RESULTS:
      Significant increasd levels of urinary PCX were found in children with acute PNS
      compared with those in the remission stage and the control group (P<0.01). A
      positive correlation was found between urinary PCX and 24 hour urinary protein in
      children with acute PNS (r=0.39, P<0.01). In children with acute PNS, urinary PCX
      levels were significantly higher in the nephritic NS group than in the simple NS
      group (P<0.05). In children in the remission stage, a significant increase in
      levels of urinary PCX was found in children who had relapsed compared with those
      who had not (P<0.05). The area under the ROC curve for the diagnosis of acute PNS
      and nephritic NS was 0.915 and 0.784 respectively. The optimal operating point
      for the diagnosis of acute PNS and nephritic NS was 7.97 and 10.28 ng/mL
      respectively, with a sensitivity and specificity of 81.1% and 93.4% respectively
      for acute PNS and of 94.1% and 52.8% respectively for nephritic NS. CONCLUSIONS:
      The quantitative detection of urinary PCX is useful in the evaluation of podocyte
      dynamic changes. It is helpful in the diagnosis of acute PNS and in the
      differentiation of nephritic NS and simple NS.

PMID- 22613102
TI  - [Clinical analysis of organic acidemia in neonates from neonatal intensive care
      units].
AB  - OBJECTIVE: To study the clinical features of organic acidemia in neonates
      admitted to the intensive care unit. METHODS: The clinical features of neonates
      from 15 neonatal intensive care units of Henan Province, who were diagnosed with
      congenital organic acidemia by gaschromatography-mass spectrometry (GC-MS)
      between June 2008 and August 2011 were retrospectively reviewed. RESULTS: Fifty
      neonates of 287 high risk neonates were confirmed as having or highly suspected
      to have inborn errors of metabolism. Of the 50 cases, 32 cases were diagnosed
      with organic acidemia disease, including 28 cases of methylmalonic acidemia, 2
      cases of propionic acidemia, 1 case of maple syrup urine disease and 1 case of
      isovaleric acldemla. In most cases, disease onset occurred in the first week
      after birth in most of cases (75%). Neonates whose symptoms occurred immediately
      after or within a few hours of birth presented with serious conditions. Clinical
      manifestations were various and mainly related to neurologic, respiratory and
      gastrointestinal symptoms such as poor response, coma, drowsiness, abnormal
      muscle tone, convulsions, polypnea, dyspnea, milk refusal, diarrhea and jaundice.
      Initial symptoms were non-specific and included dyspnea, poor response, milk
      refusal, lethargy and seizures. CONCLUSIONS: Methylmalonic acidemia is a common
      inherited metabolic disease in the neonatal period. Clinical manifestations of
      organic acid metabolism abnormalities in neonates are atypical and early onset is
      associated with more serious conditions.

PMID- 22613103
TI  - [Therapeutic effects of levetiracetam on electrical status epilepticus during
      sleep in children].
AB  - OBJECTIVE: To study the efficacy of levetiracetam (LEV) in the treatment of
      electrical status epilepticus during sleep (ESES) in children. METHODS: The
      clinical data of 27 children who were newly diagnosed with ESES and treated with
      LEV between August 2009 and March 2011 and who were followed up for at least 6
      months were retrospectively studied. RESULTS: The onset age of the 27 children
      ranged from 9 months to 9 years and 7 months. Partial motion seizures were found
      in 81% of the children in the early stage. Twenty-three children received LEV
      treatment after ESES was definitely diagnosed. Of the 23 children, 19 were
      diagnosed as epilepsy syndrome of benign childhood epilepsy with centrotemporal
      spikes (BECT). The age of the patients at the beginning of LEV treatment ranged
      from 1 year and 8 months to 11 years and 9 months. The follow- up duration was 7
      to 19 months. The effective rate of LEV for seizure control was 82% and for EEG
      recovery it was 78% (P<0.05). The other 4 children received LEV treatment before
      the occurrence of ESES. Seizure control and EEG recovery were noted in two of the
      4 children. CONCLUSIONS: LEV treatment is efficacious, to some extent, for both
      seizure control and EEG recovery in children with ESES.

PMID- 22613105
TI  - [Application of bacterial cultures of bronchoalveolar lavage fluids in children
      with pulmonary infection].
AB  - OBJECTIVE: To study the value of bacterial cultures of bronchoalveolar lavage
      fluids (BALF) in children with pulmonary infection. METHODS: Bacterial cultures
      sampled from both sputum and BALF were performed on 80 hospitalized children with
      pulmonary infection between June 2008 and February 2011.Culture results between
      the two samples were compared. RESULTS: In the 80 children with pulmonary
      infection, bacterial cultures of BALF showed that Viridans Streptococci were
      found in 72 cases (90%), Neisseria in 41 cases (51%), Streptococcus pneumoniae in
      11 cases (14%), Staphylococcus Aureus in 3 cases (4%) and Escherichia coli in 3
      cases (4%). The positive rates of Viridans Streptococci in the bacterial cultures
      of BALF was not significantly different from the bacterial cultures of sputum,
      but the positive rate of Streptococcus pneumoniae in the bacterial cultures of
      BALF was significantly higher than in the bacterial cultures of sputum (4%).
      Moreover, Escherichia coli were found only by bacterial cultures of BALF.
      CONCLUSIONS: Bacterial cultures of BALF are useful in the identification of
      pathogenic bacteria for pulmonary infection in children. Due to the samples taken
      from the lesion regions in bacterial cultures of BALF, the results of may be more
      reliable.

PMID- 22613104
TI  - [Prospective clinical study of radix astragali and its compound prescription for
      treatment of beta-thalassemia in children].
AB  - OBJECTIVE: To evaluate the efficacy and safety of radix astragali and its
      compound prescription for treatment of beta-thalassemia in children. METHODS:
      This study was a randomized, controlled, double-blind clinical trial. Fifty-seven
      children with beta-thalassemia were randomly assigned to radix astragali,
      compound prescription (radix astragali+ codonopsis pilosula + tortoise plastron)
      and placebo control groups after stratifying the patients according to disease
      type (intermedia and major). The parameters of hematology and safety were
      assessed after 12 weeks of treatment. RESULTS: After 12 weeks of treatment, the
      mean Hb elevation levels in children with beta-thalassemia intermedia from the
      compound prescription and the radix astragali groups were 1.21+/-1.12 and 1.05+/
      0.80 g/dL respectively compared with -(0.28+/-0.51) g/dL in the placebo control
      group (P<0.01). Mean Hb levels in the compound prescription and radix astragali
      groups were significantly higher than in the placebo control group (P<0.05).
      Therapy with both radix astragali and its compound prescription increased fetal
      hemoglobin, red blood cell, mean corpuscular hemoglobin and reticulocyte levels
      in children with beta-thalassemia intermedia. The total effective rates were 64%
      and 62% in children with beta-thalassemia intermedia from the compound
      prescription and radix astragali groups respectively, which was significantly
      higher than in the placebo control group (9%; P<0.01). Therapy with radix
      astragali or its compound prescription in children with beta-thalassemia major
      had similar but less favourable effects than the same therapy in children with
      beta-thalassemia intermedia. White blood cell, neutrophil, platelet and hepatic
      and renal functions were not adversely affected by the medicines. CONCLUSIONS:
      Therapy with radix astragali or its compound prescription is effective and safe
      in children with beta-thalassemia.

PMID- 22613106
TI  - [Genotype and phenotype polymorphisms of NAT2 and CYP2E1 in the Han Chinese
      pediatric population].
AB  - OBJECTIVE: N-acetyltransferase 2 (NAT2) and cytochrome P450 2EI (CYP2E1) play a
      crucial role in the drug metabolic process. The aim of this study was to
      understand the genotype and phenotype polymorphisms of NAT2 and CYP2E1 in the Han
      Chinese pediatric population in order to provide a theoretical basis for
      individualized drug treatment. METHODS: A total of 341 (211 males and 130
      females) randomly sampled Han Chinese children, aged from 2 months to 14 years,
      were enrolled in this study. Genotyping was carried out by PCR method, and
      metabolic phenotypes were identified. RESULTS: In this study population, wild
      genotype was found as a major genotype in seven SNPs of NAT2, rs1801279,
      rs1041983, rs1801280, rs1799929, rs1799930, rs1208 and rs1799931. The frequency
      of NAT2 fast metabolism was highest (61.3%), followed by middle to slow
      metabolism (34.1%). Wild genotype also predominated in the four SNPs of CYP2E1
      (rs2031920, rs3813867, rs6413432 and rs72559720) named as CYP2E1*5, *6 and *2,
      with a frequency of 61.3%, 60.1% and 99.4% respectively. As the relationship
      between CYP2E1 genotype and phenotype was unknown, phenotyping of CYP2E1 was not
      done. CONCLUSIONS: The important SNPs of NAT2 and CYP2E1 are predominantly wild
      genotype in the Han Chinese pediatric population. Fast metabolic phenotype
      predominates in important SNPs of NAT2.

PMID- 22613107
TI  - [Effects of inhaled corticosteroids on bone age and growth in children with
      asthma].
AB  - OBJECTIVE: Long-term inhaled corticosteroids are the preferred treatment for
      asthma, but their safety still controversial. The aim of the present study was to
      explore the effects of inhaled corticosteroids on bone age and growth in children
      with asthma. METHODS: Seventy-three children with asthma received inhaled
      fluticasone treatment at a starting dosage of 250 MUg/d for 3 months, when the
      dosage was reduced by a third. Three months later, the patients were treated with
      fluticasone at a dosage of 125 MUg/d for 6 months. Bone age, heights and weights
      were measured before and one year of treatment. RESULTS: The increase in the
      heights, weights and RUS (radius, ulna and short finger bones) bone age of the
      children with asthma after one year of treatment was not significantly different
      from healthy children. There were no significant differences in  body mass index
      (BMI) before and after one year of treatment, however the level of carpal bone
      age [-0.2(-0.6,0.8) years] was delayed after therapy compared to before treatment
      [-0.5(-1.0,0.6) years]  (P<0.05). CONCLUSIONS: Treatment with inhaled
      corticosteroids for 1 year may suppress the level of carpal bone age, but the
      level of RUS bone age, heights, weights and BMI are not affected. It is necessary
      to monitor the growth of children with asthma who receive long-term inhaled
      corticosteroid treatment.

PMID- 22613108
TI  - [Blood pressure levels of 2438 Hasakh children in the Yili region of Xinjiang
      Province].
AB  - OBJECTIVE: To study blood pressure levels, the prevalence of hypertension and
      factors associated with the development of hypertension in Hasakh children in the
      Yili region of Xinjiang Province. METHODS: A total of 2438 Hasakh school children
      from the Yili region of Xinjiang Province were sampled by stratified random
      cluster sampling method between May and June 2009. Height, weight, waist
      circumference, hip circumference, skinfold thickness and blood pressure were
      measured. Body mass index (BMI) was calculated. RESULTS: Mean systolic blood
      pressure (SBP) and diastolic blood pressure (DBP) were 94+/-13 mm Hg and 60+/-9
      mm Hg respectively in the 2438 children, and both averages were lower than in the
      Han children. Hypertension was noted in 138 children (5.66%). The prevalence of
      hypertension in girls (6.97%, 84/1206) was higher than in boys (4.38%, 54/1232)
      (P<0.05). The prevalence of hypertension and blood pressone were positively
      correlated with BMI, waist circumference, hip circumference, skinfold thickness
      circumference, gender and age. CONCLUSIONS: Average blood pressure levels in
      Hasakh children in the Yili region of Xinjiang Province are lower than in
      domestic age-matched Han children. The prevalence of hypertension in girls is
      higher than in boys. Obesity is highly correlated with the development of
      hypertension.

PMID- 22613109
TI  - [Effect of 1,25-(OH)2D3 supplementation during gestation and lactation on TGF
      beta1 and Smad3 expression in lungs of rat offspring with asthma].
AB  - OBJECTIVE: To study the effect of 1,25-(OH)2D3 supplementation during gestation
      and lactation on TGF-beta1 and Smad3 expression in lungs of rat offspring with
      asthma. METHODS: Thirty-two female Wistar rats were randomly divided into four
      groups: low-, medium- and high-dose 1,25-(OH)2D3 supplementation and control
      groups (n=8 each). From the 7th day of gestation, the three 1,25-(OH)2D3
      supplementation groups were administered with 2,10 and 20 MUg/mL of 1,25-(OH)2D3
      respectively every other day until weaning (rat offspring: 21 days old). The
      control group received normal saline instead. Then, bronchial asthma was induced
      in rat offspring from the 4 groups. The protein and mRNA expression of TGF-beta1
      and Smad3 in the lung tissue was measured by immunochemistry and RT-PCR. RESULTS:
      Eosinophil cell infiltration and airway inflammation decreased in rat offspring
      from the low- and medium-dose 1,25-(OH)2D3 groups, but increased in rat offspring
      of the high-dose 1,25-(OH)2D3 group compared with the control group.
      Immunohistochemistry of lung tissues showed that the expression of TGF-beta1
      protein and pSmad3 decreased in rat offspring from the low- and medium-dose 1,25
      (OH)2D3 groups (P<0.05), but increased significantly in rat offspring from the
      high-dose 1,25-(OH)2D3 group compared with the control group (P<0.05). PCR showed
      that the expression of TGF-beta1 and Smad3 mRNA in the lung tissue decreased in
      rat offspring from the low- and medium-dose 1,25-(OH)2D3 groups (P<0.05), but
      increased significantly in rat offspring from the high-dose 1,25-(OH)2D3 group
      compared with the control group (P<0.05). CONCLUSIONS: 1,25-(OH)2D3
      supplementation plays a role in regulating the immune system in asthmatic rats.
      Its mechanism may be associated with regulation of the expression of TGF
      beta/Smad signal pathway-related proteins through the vitamin D receptor signal
      pathway.

PMID- 22613111
TI  - [Level of brain-derived neurotrophic factor in the microenvironment of the neuron
      astrocyte co-culture system by Mg2+-free-induced seizure-like discharge].
AB  - OBJECTIVE: To study the level of brain-derived neurotrophic factor (BDNF) in the
      microenvironment of the neuron-astrocyte co-culture system by Mg2+-free-induced
      seizure-like discharge and analyze the source of BDNF. METHODS: Hippocampal
      neurons (N) of fetal rats and astrocytes (AST) of neonatal rats were purified and
      divided into four groups, included control N (Con N) group, Mg2+-free treated N
      (Mg2+-free N) group, control N+AST co-culture (Con N+AST) group and Mg2+-free
      treated N+AST co-culture (Mg2+-free N+AST) group. The Mg2+-free treated groups
      were exposed to Mg2+-free media for 3 hrs to induce a repeated spontaneous
      seizure-like discharge. The level of BDNF in each group at different time points
      was measured using ELISA. RESULTS: The cellular morphous of AST changed in the
      Mg2+-free N+AST group at 48 hrs. Neuronal epileptiform activity was observed in
      the Mg2+-free media at 3 hrs, and continued to exist until the microenvironment
      returned to normal for 72 hrs. The BDNF level increased at 24 hrs and 48 hrs in
      the Con N+AST group compared with the control N group (P<0.05). Compared with Con
      N+AST group, BDNF level increased at 12, 24 and 48 hrs in the Mg2+-free N+AST
      group, especially at 12 and 24 hrs (P<0.01). There were no significant
      differences in the level of BDNF between the Con and Mg2+-free N groups. Compared
      with Mg2+-free N group, BDNF level increased at 24 hrs in the Mg2+-free N+AST
      group (P<0.05). CONCLUSIONS: The results of the experiment suggest that BDNF in
      the Con N+AST group might be excreted from both N and AST, but chiefly from N.
      Activated AST may be the main source for increasing BDNF in the Mg2+-free N+AST
      group.

PMID- 22613110
TI  - [Effects of andrographolide on the expression of eosinophil granulocytes and
      possible mechanisms].
AB  - OBJECTIVE: Andrographolide, the active component in andrographis paniculata, has
      potent anti-inflammatory actions. This study aimed to evaluate the effects of
      andrographolide on eosinophil granulocytes (EOS) and the expression of eotaxin
      and IL-5 in mice with asthma. METHODS: BALB/c mice were randomly assigned into
      normal control, asthma, budesonide treatment and andrographolide treatment groups
      (n=8 each). Mice in the latter three groups were sensitized and challenged with
      ovalbumin (OVA) to induce asthma. ELISA was used to detect the concentrations of
      eotaxin and IL-5 in bronchoalveolar lavage fluid (BALF) and peripheral blood. The
      expression of eotaxin mRNA and IL-5 mRNA in lung tissues was detected by real
      time quantitative PCR. RESULTS: Andrographolide treatment significantly decreased
      EOS count in BALF (P<0.05) and the effect of andrographolide was better than the
      effect of budesonide. Andrographolide treatment significantly down-regulated the
      expression of eotaxin and IL-5 in BALF, lung eotaxin mRNA expression and blood IL
      5 expression (P<0.05), but the effects of andrographolide were poorer than the
      effects of budesonide. Andrographolide treatment resulted in a decrease in blood
      eotaxin expression and lung IL-5 mRNA expression and the effects of
      andrographolide were similar to budesonide. CONCLUSIONS: Andrographolide can down
      regulate the expression of IL-5 and eotaxin and thus suppress the inflitration of
      EOS in a mouse model of asthma.

PMID- 22613113
TI  - [Thrombophlebitis of deep veins of lower extremity in a neonate born to a
      diabetic mother].

PMID- 22613112
TI  - [Long-term behavioral and ultrastructural alterations following hypoxic-ischemic
      brain damage in neonatal rats].
AB  - OBJECTIVE: To study long-term behavioral and ultrastructural alterations in a
      hypoxic-ischemic brain damage (HIBD) model of neonatal rats. METHODS: Sixty seven
      day-old Sprague-Dawley rats were randomly subjected to unilateral carotid artery
      ligation followed by hypoxic exposure (HIBD group) or sham operation (n=30 each).
      A battery of behavioral tests, including Morris water maze test and sensorimotor
      tests, were performed at a postnatal age of 5 weeks. Nissl staining was used for
      counting neurons. Transmission electron microscopy was used for observing synapse
      structures and measuring the thickness of the postsynaptic density area and the
      length of the postsynaptic active area. The correlations of histological changes
      with the results of behavioral tests were evaluated. RESULTS: The HIBD group
      showed a significantly longer escape latency (P<0.05) and a lower frequency of
      original platform crossing (P<0.05) in the Morris water maze test compared with
      the sham operation group. The sensorimotor function test showed that the
      sensorimotor function in the HIBD group was worse than in the sham operation
      group. Nissl staining showed that the number of neurons in the HIBD group was
      significantly reduced (P<0.01) compared with the sham operation group.
      Transmission electron microscopy showed that synapses were significantly reduced
      in number, and that the thickness of the postsynaptic density area and the length
      of the postsynaptic active area were reduced in the HIBD group. The thickness of
      the postsynaptic density area was negatively correlated with escape latency in
      the Morris water maze test (r=-0.861, P<0.01), and also negatively correlated
      with the total score of sensorimotor function tests (r=-0.758, P<0.05) in the
      HIBD group. CONCLUSIONS: Hypoxia ischemia can lead to neuron loss and
      ultrastructure damage, resulting in long-term deficit of behavioral functions in
      neonatal rats.

PMID- 22613114
TI  - [Diffue large B-cell lymphoma in a child treated by rituximab complicated with
      chemotherapy].

PMID- 22613116
TI  - [Advances in research on extra-oesophageal symptoms of pediatric gastroesophageal
      reflux].
AB  - The manifestations of pediatric gastroesohageal reflux (GER) are varied and
      complex. Extra-oesophageal symptoms, including GER-related respiratory diseases,
      ear, nose and throat diseases, oral diseases and neuropsychiatric symptoms, are
      thought to be major manifestations of pediatric GER, but the causal relationship
      between GER and these extra-oesophageal symptoms is still unclear. Therefore, we
      describe the progress of research on the relationship between GER and asthma,
      chronic cough, laryngitis, pharyngitis, laryngeal papilloma, sinusitis, otitis
      media, dental erosion, apparent life-threatening event, and the crying baby
      syndrome in this review. It provides new strategies for the diagnosis and
      treatment of GER-related diseases in children.

PMID- 22613115
TI  - [A case report of plastic bronchitis].

PMID- 22613117
TI  - [Side effects of phototherapy for neonatal hyperbilirubinemia].
AB  - Blue light has been widely used for the treatment of neonatal hyperbilirubinemia
      since the 1950s. Neonatal phototherapy can decrease plasma unconjugated bilirubin
      level, thus preventing bilirubin encephalopathy, and greatly reduces the exchange
      transfusion rate. Generally, it is accepted that the side effects of neonatal
      phototherapy are not serious and seem to be well controlled, however recent
      research has provided new evidence. The short-term side effects of phototherapy
      include interference with maternal-infant interaction, imbalance of thermal
      environment and water loss, electrolyte disturbance, bronze baby syndrome and
      circadian rhythm disorder. In addition, phototherapy may be associated with some
      long-term side effects such as melanocytic nevi and skin cancer, allergic
      diseases, patent ductus arteriosus and retinal damage. Therefore, it is necessary
      to develop evidence-based guidelines, new light devices and alternative agents,
      as well as individualized treatments, to minimize the side effects of
      phototherapy.

PMID- 22613118
TI  - Trends in perinatal health in France from 1995 to 2010. Results from the French
      National Perinatal Surveys.
AB  - OBJECTIVE: To study trends in the main indicators of health, medical practices
      and risk factors in France. POPULATION AND METHOD: We collected data from samples
      of all births in France during one week in 1995 (n=13318), 1998 (n=13718), 2003
      (n=14737) and 2010 (n=14903) and have compared them. RESULTS: Between 1995 and
      2010, maternal age and body mass index increased steadily, but tobacco use
      decreased. In 2010, 39.4% of pregnant women had a visit with a midwife in a
      maternity unit, versus 26.6% in 2003. Deliveries occurred in large public
      hospitals more and more frequently. The increase in caesarean sections was no
      longer significant between 2003 and 2010. In general, medical decisions during
      pregnancy and delivery were closer to professional recommendations in 2010 than
      in earlier years. Live births before 37 weeks increased steadily from 5.4% in
      1995 to 6.6% in 2010, but the proportion of birth weights below 2500g or the 10th
      percentile stopped increasing after 2003. CONCLUSION: Routine national perinatal
      surveys highlight major trends in maternal characteristics, obstetric practices,
      organisation of services, and perinatal health.

PMID- 22613119
TI  - The influence of substituent effects on spectroscopic properties examined on
      benzylidene aniline-type imines.
AB  - Six selected benzylidene aniline-type prochiral imines were characterised by
      means of ATR-IR, UV-vis and Raman spectroscopy. A detailed UV-vis spectroscopic
      study supported by data obtained from single crystal X-ray analysis reveals the
      influence of the conformation of the imine on the electronic state. Additionally,
      the electronic effects of the substituents located in 4,4'-position on the shape
      of the UV-vis spectra were discussed. The influence of the substituents on the
      vibrational state of the CN double bond has been studied by ATR-IR spectroscopy
      using solid and dissolved samples. Finally, solvatochromatism and solvent
      introduced tautomerism have been investigated by UV-vis and Raman spectroscopy.
      The effect of inter- and intramolecular hydrogen bond formation was demonstrated
      by changes of characteristic bands in the spectra.

PMID- 22613120
TI  - Squarylium-based chromogenic anion sensors.
AB  - A squarylium (SQ) dye was synthesized by the reaction between squaric acid and
      2,3,3-trimethylindolenine and its anion sensing properties were investigated
      using absorption and emission spectroscopy. This chemosensor exhibited high
      selectivity for CN(-) as compared with F(-), CH(3)CO(2)(-), Br(-), H(2)PO(4)(-),
      Cl(-), and NO(3)(-) in acetonitrile, which was attributed to the formation of a
      1:1 squarylium:CN(-) coordination complex, the formation of which was supported
      by the calculated geometry of the complex.

PMID- 22613121
TI  - A novel tridentate Schiff base dioxo-molybdenum(VI) complex: synthesis,
      experimental and theoretical studies on its crystal structure, FTIR, UV-visible,
      1H NMR and 13C NMR spectra.
AB  - A new dioxo-molybdenum(VI) complex [MoO(2)(L)(H(2)O)] has been synthesized, using
      5-methoxy 2-[(2-hydroxypropylimino)methyl]phenol as tridentate ONO donor Schiff
      base ligand (H(2)L) and MoO(2)(acac)(2). The yellow crystals of the compound are
      used for single-crystal X-ray analysis and measuring Fourier Transform Infrared
      (FTIR), UV-visible, (1)H NMR and (13)C NMR spectra. Electronic structure
      calculations at the B3LYP and PW91PW91 levels of theory are performed to optimize
      the molecular geometry and to calculate the UV-visible, FTIR, (1)H NMR and (13)C
      NMR spectra of the compound. Vibrational assignments and analysis of the
      fundamental modes of the compound are performed. Time-dependent density
      functional theory (TDDFT) method is used to calculate the electronic transitions
      of the complex. All theoretical methods can well reproduce the structure of the
      compound. The (1)H NMR shielding tensors computed at the B3LYP/DGDZVP level of
      theory is in agreement with experimental (1)H NMR spectra. However, the (13)C NMR
      shielding tensors computed at the B3LYP level, employing a combined basis set of
      DGDZVP for Mo and 6-31+G(2df,p) for other atoms, are in better agreement with
      experimental (13)C NMR spectra. The electronic transitions calculated at the
      B3LYP/DGDZVP level by using TD-DFT method is in accordance with the observed UV
      visible spectrum of the compound.

PMID- 22613122
TI  - Vibrational spectra of silatranes and germatranes XM(OCH2CH2)3N (X=F,Cl,H;
      M=Si,Ge). The problem of the theoretical prediction of condensed phase spectra.
AB  - The structures of silatranes and germatranes XM(OCH(2)CH(2))(3)N (X=F,Cl,H;
      M=Si,Ge) were optimized and their vibrational spectra were calculated at the
      B3LYP/aug-cc-pVDZ level of theory. Theoretical frequencies of vibrations
      perpendicular to the C(3) axis (E type) are in good agreement with experimental
      values, while the axial vibrations (MX and M...N stretchings) demonstrate a
      significant discrepancy with experimental spectra recorded for the crystalline
      state. This discrepancy stems from the well-known difference in the MX and M...N
      bond lengths in gas and solid state. The force constant scaling procedure was
      used to compensate for this difference. As a result a set of scaling factors was
      refined for 1-Cl-germatrane (the unique atrane for which the distinction between
      A and E modes was experimentally established). This set was transferred to the
      theoretical force fields of other atranes, which provided a fair reproduction of
      their experimental frequencies. The analysis of the normal modes allowed us to
      assign the nu M...N mode to bands in the 180-270 cm(-1) frequency range, although
      large contributions of these coordinates are in two other modes in the 450-500
      cm(-1) and 600-800 cm(-1) frequency ranges. The frequencies of degenerate
      vibrations (with vectors perpendicular to the C(3) axis) do not depend
      substantially on the axial atom (X and M) substitution, while those of A-type in
      the 200-700 cm(-1) frequency range vary significantly.

PMID- 22613123
TI  - Simultaneous first order derivative spectrophotometric determination of vanadium
      and zirconium in alloy steels and minerals.
AB  - A simple, selective and sensitive spectrophotometric method has been developed
      for the individual and simultaneous determination of trace amounts of vanadium(V)
      and zirconium(IV) in acetic acid medium using a newly synthesised reagent
      diacetylmonoxime salicyloylhydrazone (DMSH), without any prior separation. The
      molar absorptivity and Sandell's sensitivity of the coloured species are 1.30 x
      10(4) and 1.82 x 10(4) L mol(-1)cm(-1) and 3.9 and 2.5 ng cm(-2) for V(V) and
      Zr(IV), respectively. Beer's law is obeyed between 0.26-2.80 and 0.30-3.20 MUg
      mL(-1) concentration of vanadium (V) and zirconium (IV) at 405 and 380 nm
      respectively. The stoichiometry of the complex was found to be 1:1 (metal:ligand)
      for V(V) and 1:2 for Zr(IV) complexes. These metal ions interfere with the
      determination of each other in zero order spectrophotometry. The first derivative
      spectra of these complexes permitted a simultaneous determination of V(V) and
      Zr(IV) at zero crossing wavelengths of 445 nm and 405 nm, respectively. The
      optimum conditions for maximum colour development and other analytical parameters
      were evaluated. The proposed method has been successfully applied for the
      determination of zirconium and vanadium in standard alloy steel samples, mineral
      and soil samples.

PMID- 22613124
TI  - Using ATR-FT/IR molecular spectroscopy to detect effects of blend DDGS inclusion
      level on the molecular structure spectral and metabolic characteristics of the
      proteins in hulless barley.
AB  - The objectives of this study were to investigate the effects of inclusion of a
      bioethanol co-product of blend DDGS (wheat:corn=70%:30%) on protein molecular
      structure spectral and metabolic characteristics in hulless barley-based feed
      using ATR-FT/IR molecular spectroscopy. Hulless barley grain with the blend DDGS
      were mixed in the five ratios. The results showed that when blend DDGS was
      included at an increased ratio, predicted truly absorbed protein supply was
      highly and linearly increased (P<0.05) from 98 to 245 g kg(-1) DM and degraded
      protein balance was increased (P<0.05) from -1 to 75 g kg(-1) DM. The ratio of
      amide I to II peak area was increased (P<0.05) in the original combination
      samples but decreased (P<0.05) in the in situ 48 h residue samples. The ratio of
      alpha-helix to beta-sheet peak height was quadratically changed with increasing
      inclusion rate of blend DDGS in the original samples, but no difference among the
      in situ 48 h residue samples, indicating completion of protein degradation. No
      correlation was found between protein 2nd structures and protein nutrient
      profiles not only for the original combination samples (except NPN) but also for
      in situ 48 h residue samples. This study may provide information on how protein
      molecular structure and metabolic characteristic changes after feed combination
      and how more effectively utilize hulless barley and blend co-products for dairy
      and beef cattle.

PMID- 22613125
TI  - alpha-Bromo-2,6-dichlorotoluene: molecular structure, vibrational spectroscopy,
      natural bond orbital analysis and NMR studies.
AB  - The FT-IR and FT-Raman spectra of alpha-bromo-2,6-dichlorotoluene (alphaBDCT)
      have been recorded. The structural and spectroscopic data of the molecule in the
      ground state have been calculated using Hartree Fock (HF) and Density Functional
      Theory (DFT)/B3LYP with the standard 6-31++G(d,p) basis set. The optimized
      molecular geometry, vibrational frequencies and atomic charges in the ground
      state are calculated. With the help of specific scaling procedures, the observed
      vibrational wavenumbers in FT-IR and FT-Raman spectra have been analyzed and
      assigned to different normal modes of the molecule. A detailed interpretation of
      the infrared and Raman spectra of alphaBDCT is also reported based on total
      energy distribution (TED). The (1)H and (13)C NMR chemical shifts have been
      calculated by gauge-including atomic orbital method with B3LYP/6-31++G(d,p)
      approach. Stability of the molecule arising from hyperconjugative interactions
      and charge delocalization has been analyzed using natural bond orbital (NBO)
      analysis. The theoretical results agree well with the observed spectra.

PMID- 22613126
TI  - Synthesis, growth, spectral and thermal properties of a new organic crystal: 2
      carboxypyridin-1-ium trichloroacetate.
AB  - A novel organic optical material complex of 2-carboxypyridin-1-ium
      trichloroacetate has been synthesized and crystals were grown from aqueous
      solution employing the technique of controlled evaporation. The crystal structure
      has been determined using single crystal X-ray diffraction studies. The single
      crystals were successfully grown by the slow evaporation method with dimensions
      12 * 8 * 3 mm(3). FT IR spectral investigation has been carried out to identify
      the various functional groups present in the grown crystal. Molecular structure
      was confirmed by NMR spectral analysis. Melting point was found using thermal
      measurements.

PMID- 22613127
TI  - Luminescence and binding properties of two isoquinoline alkaloids chelerythrine
      and sanguinarine with ctDNA.
AB  - The binding mode and mechanism of the interactions between two planar cationic
      alkaloids chelerythrine (Che) and sanguinarine (San) with calf thymus DNA (ctDNA)
      were systematically investigated at pH 5.40 using UV-vis absorption spectroscopy,
      fluorescence spectroscopy and cyclic voltammetry. Che and San show strong
      fluorescence at 570 and 589 nm, respectively. Che displays fluorescence
      enhancement with ctDNA whereas the fluorescence of San is quenched on interaction
      with ctDNA. In addition, UV-vis spectra of both alkaloids show apparent
      hypochromicity and are bathochromic shifted, indicating that they could
      intercalate into ctDNA bases. The fluorescence polarization of Che and San
      increases in the presence of ctDNA, again implying the intercalation of two
      alkaloids with ctDNA. This conclusion was also supported by the results obtained
      from anion quenching and cyclic voltammetry. The binding constants of both
      alkaloids with ctDNA were calculated in the order of 10(5)L/mol. San binds with
      ctDNA 3-fold stronger than Che. The stoichiometric bindings are five nucleotides
      per Che or San. Electrostatic binding also exists between the alkaloids and DNA
      helix. Finally, theoretical calculations show that only certain parts of Che and
      San molecules intercalate into the DNA helix.

PMID- 22613129
TI  - Indole-3-acetic acid biosensor based on G-rich DNA labeled AuNPs as
      chemiluminescence probe coupling the DNA signal amplification.
AB  - A highly sensitive chemiluminescence (CL) method for detection of phytohormone
      indole-3-acetic acid (IAA) was developed by using G-rich DNA labeled gold
      nanoparticles (AuNPs) as CL probe coupling the DNA signal amplification
      technology. The IAA antibody was immobilized on carboxyl terminated magnetic
      beads (MBs). In the presence of IAA, antibody labeled AuNPs were captured by
      antibody functionalized MBs. The DNA on AuNPs is released by a ligand exchange
      process induced by the addition of DTT. The released DNA is then acted as the
      linker and hybridized with the capture DNA on MBs and probe DNA on AuNPs CL
      probe. The CL signal is obtained via the instantaneous derivatization reaction
      between a specific CL reagent, 3,4,5-trimethoxyl-phenylglyoxal (TMPG), and the G
      rich DNA on AuNPs CL probe. IAA can be detected in the concentration range from
      0.02 ng/mL to 30 ng/mL, and the limit of detection is 0.01 ng/mL.

PMID- 22613128
TI  - Antioxidant properties of various solvent extracts from purple basil.
AB  - Water, ethanol and acetone extracts from leaves and flowers of purple basil, one
      of the most popular spices consumed in the Thrace region of Turkey, were tested
      in vitro for their ability to inhibit peroxidation of lipids, to scavenge DPPH,
      hydrogen peroxide, superoxide anion, to reduce Fe(III) to Fe(II) and to chelate
      Fe(II) ions. The results showed that purple basil contained naturally occurring
      antioxidant components and possessed antioxidant activity which may be attributed
      to its lipid peroxidation inhibitory, radical scavenging and metal chelating
      activities. It was concluded that purple basil might be a potential source of
      antioxidants.

PMID- 22613130
TI  - Changes in depressive symptoms and functional disability among community-dwelling
      depressive older adults.
AB  - BACKGROUND: Previous studies have shown that the presence of depressive symptoms
      among older persons was evidently associated with subsequent physical and
      functional decline. However, few studies have directly examined the impact of
      changes in depressive symptoms or depressed mood on changes in functional
      ability. The present prospective study examined whether changes in the levels and
      remission of depressive symptoms were associated with changes in functional
      ability among community-living older persons who were treated for depressive
      symptoms in a primary care setting. METHODS: Older persons aged 60 and above with
      depressive symptoms (N = 267) were followed up in a primary care treatment
      program over 12 months. Geriatric Depression Scale (GDS-15), and instrumental and
      basic activities of daily living (IADL and ADL) were measured at baseline and at
      12-month follow-up. The associations of GDS change scores and conversion to non
      depressed status with ADL and IADL change scores, controlling for baseline
      covariates including chronic medical comorbidity and Mini-Mental State
      Examination (MMSE), were examined in multiple regression analyses. RESULTS: An
      improvement in GDS scores (baseline score minus 12-month score) was significantly
      associated with improvement (12-month score minus baseline score) in ADL (beta =
      0.355, p < 0.001) and IADL scores (beta = 0.165, p = 0.018) after adjusting for
      baseline functional status, MMSE, chronic medical comorbidities, and other
      variables. In particular, conversion in GDS status to "non-depressive" state (GDS
      <=4) was associated with an improvement in ADL change scores (beta = 0.281, p =
      0.019). CONCLUSION: In depressed older persons, an improvement in depressive
      symptoms was associated with improved functional ability.

PMID- 22613131
TI  - Electroacupuncture inhibits CB1 upregulation induced by ethanol withdrawal in
      mice.
AB  - CB1R play a role in alcohol withdrawal and in some effects of acupuncture.
      Interestingly, acupuncture has been used to alleviate alcohol withdrawal. Here,
      we investigated electroacupuncture (EA) effects during ethanol withdrawal on CB1R
      immunoreactivity. Male Swiss mice were daily injected with ethanol (2g/kg, i.p)
      (EtOH group), for 21 days. EA was performed daily during 4 days of ethanol
      withdrawal. The stimuli of 2 or 100 Hz were provided in two acupoints
      combination: Ea1 [(ST-36/Zusanli) and (PC-6/Neiguan)] or Ea2 [(DU-14/Dazhui) and
      (DU-20/Baihui)]. The specificity of the acupoints were assessed by the inclusion
      of three additional groups, Ea3 [(ST 25/Tianshu - acupoints used to other non
      related disorders)], Sham1 and Sham2 (transdermic stimulation nearly to the
      respective acupoints). EtOH group were only handled during withdrawal and Saline
      group was chronically treated with Saline and handled similarly to EtOH group.
      One day after withdrawal the animals were perfused and their brains processed for
      immunohistochemistry. There was an increase of CB1R in the prefrontal cortex,
      striatum, hippocampus, amygdala and ventral tegmental area. The procedures used
      in the 2HzEa1 and 100HzEa2 groups were the most effective and specific to inhibit
      this CB1R upregulation. Therefore, EA inhibits CB1R upregulation seen in ethanol
      withdrawn mice. The specificity of acupoints stimulation depends of the
      encephalic nuclei, acupoints association and frequency of stimulation.

PMID- 22613132
TI  - Inhibition of forebrain MU-opioid receptor signaling by low concentrations of
      rimonabant does not require cannabinoid receptors and directly involves MU-opioid
      receptors.
AB  - Increasing number of publications shows that cannabinoid receptor 1 (CB(1))
      specific compounds might act in a CB(1) independent manner, including rimonabant,
      a potent CB(1) receptor antagonist. Opioids, cannabinoids and their receptors are
      well known for their overlapping pharmacological properties. We have previously
      reported a prominent decrease in MU-opioid receptor (MOR) activity when animals
      were acutely treated with the putative endocannabinoid noladin ether (NE). In
      this study, we clarified whether the decreased MOR activation caused by NE could
      be reversed by rimonabant in CB(1) receptor deficient mice. In functional
      [(35)S]GTPgammaS binding assays, we have elucidated that 0.1mg/kg of
      intraperitoneal (i.p.) rimonabant treatment prior to that of NE treatment caused
      further attenuation on the maximal stimulation of Tyr-d-Ala-Gly-(NMe)Phe-Gly-ol
      (DAMGO), which is a highly specific MOR agonist. Similar inhibitory effects were
      observed when rimonabant was injected i.p. alone and when it was directly applied
      to forebrain membranes. These findings are cannabinoid receptor independent as
      rimonabant caused inhibition in both CB(1) single knockout and CB(1)/CB(2) double
      knockout mice. In radioligand competition binding assays we highlighted that
      rimonabant fails to displace effectively [(3)H]DAMGO from MOR in low
      concentrations and is highly unspecific on the receptor at high concentrations in
      CB(1) knockout forebrain and in their wild-type controls. Surprisingly, docking
      computational studies showed a favorable binding position of rimonabant to the
      inactive conformational state of MOR, indicating that rimonabant might behave as
      an antagonist at MOR. These findings were confirmed by radioligand competition
      binding assays in Chinese hamster ovary cells stably transfected with MOR, where
      a higher affinity binding site was measured in the displacement of the tritiated
      opioid receptor antagonist naloxone. However, based on our in vivo data we
      suggest that other, yet unidentified mechanisms are additionally involved in the
      observed effects.

PMID- 22613133
TI  - Attenuation of NF-kappabeta mediated apoptotic signaling by tocotrienol
      ameliorates cognitive deficits in rats postnatally exposed to ethanol.
AB  - Ethanol-induced damage in the developing brain may result in cognitive impairment
      including deficits on neuropsychological tests of learning, memory and executive
      function, yet the underlying mechanisms remain elusive. In the present study we
      investigated the protective effect of tocotrienol against cognitive deficit,
      neuroinflammation and neuronal apoptosis in rat pups postnatally exposed to
      ethanol. Pups were administered ethanol (5g/kg, 12% v/v) by intragastric
      intubation on postnatal days 7, 8 and 9. Ethanol-exposed pups showed significant
      memory impairment in Morris water maze task as evident from increase in escape
      latency and total distance travelled to reach the hidden platform. Time spent in
      target quadrant, % total distance traversed in target quadrant and frequency of
      appearance in target quadrant was also significantly decreased in ethanol exposed
      pups in probe trial. Poor memory retention was exhibited by ethanol-exposed pups
      in elevated plus maze test also. Impaired cognition was associated with
      significantly enhanced acetylcholinesterase activity, increased neuroinflammation
      (oxidative-nitrosative stress, TNF-alpha, IL-1beta and TGF-beta1) and neuronal
      apoptosis (NF-kappabeta and Caspase-3) in different brain regions of ethanol
      exposed pups. Co-administration with tocotrienol significantly ameliorated all
      the behavioral, biochemical and molecular alterations in the different brain
      regions of ethanol exposed pups. The current study thus demonstrates the possible
      involvement of NF-kappabeta mediated apoptotic signaling in cognitive deficits
      associated with postnatal ethanol exposure in rats and points to the potential of
      tocotrienol in the prevention of cognitive deficits in children with fetal
      alcohol spectrum disorders (FASDs).

PMID- 22613134
TI  - Electrical stimulation of retinal ganglion cells with diamond and the development
      of an all diamond retinal prosthesis.
AB  - Electronic retinal implants for the blind are already a market reality. A world
      wide effort is underway to find the technology that offers the best combination
      of performance and safety for potential patients. Our approach is to construct an
      epi-retinally targeted device entirely encapsulated in diamond to maximise
      longevity and biocompatibility. The stimulating array of our device comprises a
      monolith of electrically insulating diamond with thousands of hermetic,
      microscale nitrogen doped ultra-nanocrystalline diamond (N-UNCD) feedthroughs.
      Here we seek to establish whether the conducting diamond feedthroughs of the
      array can be used as stimulating electrodes without further modification with a
      more traditional neural stimulation material. Efficacious stimulation of retinal
      ganglion cells was established using single N-UNCD microelectrodes in contact
      with perfused, explanted, rat retina. Evoked rat retinal ganglion cell action
      potentials were recorded by patch clamp recording from single ganglion cells,
      adjacent to the N-UNCD stimulating electrode. Separately, excellent
      electrochemical stability of N-UNCD was established by prolonged pulsing in
      phosphate buffered saline at increasing charge density up to the measured charge
      injection limit for the material.

PMID- 22613135
TI  - Diminished adhesion and activation of platelets and neutrophils with CD47
      functionalized blood contacting surfaces.
AB  - CD47 is a ubiquitously expressed transmembrane protein that, through signaling
      mechanisms mediated by signal regulatory protein alpha (SIRPalpha1), functions as
      a biological marker of 'self-recognition'. We showed previously that inflammatory
      cell attachment to polymeric surfaces is inhibited by the attachment of
      biotinylated recombinant CD47 (CD47B). We test herein the hypothesis that CD47
      modified blood conduits can reduce platelet and neutrophil activation under
      clinically relevant conditions. We appended a poly-lysine tag to the C-terminus
      of recombinant CD47 (CD47L) allowing for covalent linkage to the polymer.
      SIRPalpha1 expression was confirmed in isolated platelets. We then compared
      biocompatibility between CD47B and CD47L functionalized polyvinyl chloride (PVC)
      surfaces and unmodified control PVC surfaces. Quantitative and Qualitative
      analysis of blood cell attachment to CD47B and CD47L surfaces, via scanning
      electron microscopy, showed strikingly fewer platelets attached to CD47 modified
      surfaces compared to control. Flow cytometry analysis showed that activation
      markers for neutrophils (CD62L) and platelets (CD62P) exposed to CD47 modified
      PVC were equivalent to freshly acquired control blood, while significantly
      elevated in the unmodified PVC tubing. In addition, ethylene oxide gas
      sterilization did not inhibit the efficacy of the CD47 modification. In
      conclusion, CD47 modified PVC inhibits both the adhesion and activation of
      platelets and neutrophils.

PMID- 22613136
TI  - Detection of coronary microembolization by Doppler ultrasound in patients with
      stable angina pectoris during percutaneous coronary interventions under an
      adjunctive antithrombotic therapy with abciximab: design and rationale of the
      High Intensity Transient Signals ReoPro (HITS-RP) study.
AB  - BACKGROUND: Embolization of atherosclerotic debris from the rupture of a
      vulnerable atherosclerotic plaque occurs iatrogenically during percutaneous
      coronary interventions (PCI) and can induce myocardial necrosis. These
      microembolizations are detected as high intensity transient signals (HITS) using
      intracoronary Doppler technology. PRESENTATION OF THE HYPOTHESIS: In the
      presented study we will test if abciximab (ReoPro(r)) infusion reduces high
      intensity transient signals in patients with stable angina pectoris undergoing
      PCI in comparison to standard therapy alone. TESTING THE HYPOTHESIS: The High
      Intensity Transient Signals ReoPro(r) (HITS-RP) study will enroll 60 patients. It
      is a prospective, single center, randomized, double-blinded, controlled trial.
      The study is designed to compare the efficacy of intravenous abciximab
      administration for reduction of microembolization during elective PCI. Patients
      will be randomized in a 1:1 fashion to abciximab or placebo infusion. The primary
      end point of the HITS-RP-Study is the number of HITS during PCI measured by
      intracoronary Doppler wire. Secondary endpoints are bleeding complications,
      elevation of cardiac biomarkers or ECG changes after percutaneous coronary
      interventions, changes in coronary flow velocity reserve, hs-CRP elevation, any
      major adverse cardio-vascular event during one month follow-up. IMPLICATIONS OF
      THE HYPOTHESIS: The HITS-RP-Study addresses important questions regarding the
      efficacy of intravenous abciximab administration in reducing microembolization
      and periprocedural complications in stable angina pectoris patients undergoing
      PCI. TRIAL REGISTRATION: The trial is registered under http://www.drks
      neu.uniklinik-freiburg.de/drks_web/:DRKS00000603.

PMID- 22613139
TI  - Nickamine: a general catalyst for cross coupling of alkyl halides and direct
      alkylation.
AB  - A nickel pincer complex, Nickamine, is shown to be an active catalyst for a large
      number of reactions including cross coupling of non-activated alkyl halides and
      direct C-H alkylation of alkynes and aromatic heterocycles. This work was
      rewarded by the 2011 Werner Prize from the Swiss Chemical Society.

PMID- 22613137
TI  - Shared resource laboratories: impact of new design criteria to consolidate flow
      cytometry diagnostic service.
AB  - INTRODUCTION: The Shared Resource Laboratory (SRL) model recently described for
      research activities would also appear to be highly suitable for diagnostic
      services. Using modern SRL design criteria and benchmarks, the aim of our study
      was to verify whether the consolidation of a diagnostic cytofluorimetric activity
      could improve the overall service. METHODS: Outcome indicators such as impact on
      analytical quality, clinical satisfaction, team work involvement, and economic
      performance were evaluated in the planning and setting up of a new central
      laboratory. Comparison with preconsolidation status allowed us to investigate
      possible indicators of improvement. RESULTS: A total of 30 140 cytofluorimetric
      analyses performed before and after consolidation at the Central Laboratory in
      Pievesestina in north-central Italy were evaluated. The overall score of the
      clinical satisfaction questionnaire (range, between 1 and 5) increased from 4.3
      to 4.9. Full-time equivalent (FTE) operators were reduced from 9 to 4.5 and
      cytofluorimeters from 6 to 2; economic indicator analyses showed a 17.75%
      reduction in unitary test costs. CONCLUSIONS: The adoption of new benchmarks and
      design criteria increased the quality of cytofluorimetric analysis, thus
      improving specialized diagnostic services and promoting the shared resource
      clinical laboratory.

PMID- 22613140
TI  - Molecular rotors image intracellular viscosity.
AB  - This review describes a new method for quantitative measurement and spatial
      imaging of microviscosity within individual domains of live cells. The method is
      based on fluorescence detection from small synthetic molecules termed 'molecular
      rotors', which are characterised by a strong response of fluorescence lifetimes
      or spectra to the viscosity of their immediate environment. We have demonstrated
      that the quantitative determination of viscosity is possible using lifetime-based
      molecular rotors and ratiometric molecular rotors. The ratiometric imaging of
      viscosity benefits from a very fast signal acquisition. We have illustrated this
      advantage by monitoring changes in intracellular viscosity during photodynamic
      therapy, which is a clinically utilised modality for the treatment of neoplastic
      disease.

PMID- 22613141
TI  - In vivo evaluation of FimH antagonists - a novel class of antimicrobials for the
      treatment of urinary tract infection.
AB  - The discovery of antimicrobials as beta-lactam antibiotics or aminoglycosides
      revolutionized the treatment of infectious diseases. However, the extensive use
      rapidly created the problem of resistant pathogens, which are increasingly
      difficult to treat. FimH antagonists are a new class  of antimicrobials, which
      target the bacterial adhesion to urothelial cells, a crucial first step in the
      establishment of urinary tract infections. Because of their different mode of
      action, FimH antagonists neither kill nor inhibit the growth of bacteria, they
      should have a reduced potential  to generate resistant strains. This mini-review
      outlines the main problems associated with increasing development of
      antimicrobial resistance. Furthermore, it summarizes the currently available in
      vivo studies in mice for the treatment of urinary tract infections conducted with
      FimH antagonists.

PMID- 22613142
TI  - Metal template synthesis of molecular knots and links.
AB  - The use of metal ions as templates to direct the assembly of complex
      architectures and topologies is briefly reviewed, highlighting milestones in the
      field from [2]catenanes, through to trefoil knots, Solomon links, Borromean rings
      and most recently to a molecular pentafoil knot.

PMID- 22613143
TI  - Excited state dynamics with quantum trajectories.
AB  - Nuclear quantum dynamics beyond the Born-Oppenheimer approximation is performed
      using quantum trajectories.
      Withintheadiabaticrepresentationoftheelectronicstates,
      NABDY(NonAdiabaticBohmianDYnamics) is used in combination with DFT and LR-TDDFT
      to perform on-the-fly nonadiabatic quantum  dynamics. Simple numerical test
      systems and current limitations of the method are discussed.

PMID- 22613144
TI  - Application of explicitly localized molecular orbitals to electronic structure
      calculations.
AB  - We have recently generalized the method for localizing orbitals on a set of
      predefined molecular fragments [Phys. Chem. Chem. Phys. 2012, 14, 546]. The
      regional localized molecular orbitals (RLMO) are well suited for exploiting the
      locality of electronic correlation at post-Hartree-Fock level of theory. In this
      paper, the adequacy of RLMO representation is tested in the second-order local
      Moller-Plesset (LMP2) perturbation theory. Two model systems, namely, n
      pentadecane and trans-retinal, are considered. Adequacy of RLMO/LMP2 method is
      discussed in conjunction with 'exact' MP2 and Pipek-Mezey LMP2 calculations. It
      is demonstrated that RLMO/MP2 method reduces correlation space and reproduces
      more than 99% of the correlation energy.

PMID- 22613145
TI  - Speed limits for acid-base chemistry in aqueous solutions.
AB  - Proton transfer reactions, including acid-base recombination, are commonly
      considered to occur 'nearly instantaneously'. However, their actual time scales
      may stretch far into the microsecond range, as acid-base reactions are diffusion
      controlled and the concentrations are  low near neutral pH. The interplay of
      competing bases in the pH relaxation is illustrated using a model acid-base
      system consisting of o-nitrobenzaldehyde (oNBA) as a proton cage and acetate ions
      and hydroxyl ions as bases. The kinetically controlled behavior leads to highly 
      counterintuitive states, i.e. acetate ions are transiently protonated for
      hundreds of nanoseconds despite the presence of a much stronger base OH-.

PMID- 22613146
TI  - Recent advances in iridium-catalyzed asymmetric hydrogenation: new catalysts,
      substrates and applications in total synthesis.
AB  - Iridium-catalyzed asymmetric hydrogenation has emerged as a highly efficient
      method for the synthesis of enantiomerically pure compounds. This account
      summarizes our recent efforts in this field. We have developed a new type of P,O
      ligand that was successfully applied to the asymmetric  hydrogenation of
      alpha,beta-unsaturated carbonyl compounds. Furthermore we have demonstrated the
      potential of known iridium catalysts in the hydrogenation of alpha,beta
      unsaturated boronic esters. And finally we could demonstrate the utility of
      iridium-catalyzed asymmetric hydrogenation  in the formal synthesis of the
      natural product Platensimycin.

PMID- 22613147
TI  - Influence of solutes on hydration and lubricity of dextran brushes.
AB  - The characteristic lubricity and non-fouling behavior of polymer brushes is
      critically dependent on the solvation of the polymer chains, as well as the chain
      chain interactions. Dextran brushes have shown promise as non-toxic aqueous
      lubricant films, and are similar in composition  to natural lubricating systems,
      while their comparative simplicity allows for controlled preparation and fine
      characterization. This project entails measuring the solvation and lubricity of
      dextran brushes in the presence of additives which modify the inter-chain
      hydrogen bonding. The thickness  and refractive index of the film were measured
      during adsorption of the brush layer onto a silica substrate and the subsequent
      immersion in solutions of potassium sulfate and alpha, alpha-trehalose. We also
      studied the lubricity of the system as a function of normal loading using
      colloidal-probe  AFM. Both solutes are shown to have a minimal effect on the
      hydration of the brush while significantly reducing the brush lubricity,
      indicating that inter-chain hydrogen bonding supports the load-bearing capacity
      of polysaccharide brushes.

PMID- 22613148
TI  - Copper-catalyzed asymmetric conjugate addition to challenging Michael acceptors
      and synthesis of relevant target molecules.
AB  - We report herein the enantioselective Cu-catalyzed conjugate addition of
      organometallic reagents to sensitive Michael acceptors and their application to
      the synthesis of relevant target molecules. This is one of the most important
      methodologies to form a C-C bond in an enantioselective  manner. A wide range of
      alpha,beta-unsaturated aldehydes and beta,gamma-unsaturated-alpha-ketoesters has
      been successfully used. Reactivity, regio- and enantioselectivities were strongly
      dependent on the reaction conditions, therefore moderate to very good results
      were obtained.  Furthermore, gamma-substituted-alpha-ketoesters were used as
      chiral building blocks for further derivatization with complete retention of the
      chiral information to obtain key compounds.

PMID- 22613149
TI  - Development of [(18)F]-PSS223 as a PET tracer for imaging of metabotropic
      glutamate receptor subtype 5 (mGluR5).
AB  - Involvement of metabotropic glutamate receptor subtype 5 (mGluR5) in
      physiological and pathophysiological processes in the brain has been
      demonstrated, and hence mGluR5 has emerged as an important drug target. [(11)C]
      ABP688 is clinically the most successful mGluR5 positron  emission tomography
      (PET) tracer to date and it allows visualization and quantification of mGluR5.
      Due to the short half-life of carbon-11, clinical use of [(11)C]-ABP688 is
      limited to facilities with an on-site cyclotron and a fluorine-18 (half-life 110
      min) analogue would be more  practical. Based on the [(11)C]-ABP688 structural
      motif, a novel derivative [(18)F]-PSS223 was prepared and evaluated as a PET
      tracer for imaging of mGluR5 in vitro and in vivo. Our results show favourable in
      vitro binding properties; however rapid defluorination  of [(18)F]-PSS223 does
      not allow visualization of mGluR5 in the rat brain.

PMID- 22613150
TI  - Heteroatom nucleophile induced C-C fragmentations to access functionalized
      allenes.
AB  - The rich structural and reactivity profile of allenes render them versatile
      synthetic intermediates. However, application of allenes in organic chemistry is
      often attenuated by inconvenient methods of preparation. Herein we present an
      operationally simple route to functionalized allenes  from vinyl triflate
      precursors through a Grob-type fragmentation induced by heteroatom nucleophiles
      such as water, alcohols, thiols or amines. The fragmentation occurs under mild
      conditions and is well suited for one-pot or domino processes allowing access to
      a range of synthetically useful  intermediates.

PMID- 22613151
TI  - Dynamical processes in Rydberg-Stark deceleration and trapping of atoms and
      molecules.
AB  - The interaction between inhomogeneous electric fields and the large electric
      dipole moments of atoms and molecules in Rydberg states of high principal quantum
      number can be used to efficiently accelerate and decelerate atoms and molecules
      in the gas phase. We describe here how hydrogen  atoms and molecules initially
      moving with velocities of ~600 m/s in supersonic beams can be decelerated to zero
      velocity and loaded into electric traps. The long observation times that are made
      possible by the electrostatic trapping enables one to study slow relaxation
      processes. Experiments  are presented in which we have observed photoionization
      processes and transitions between Rydberg states induced by blackbody radiation
      at temperatures between 10 K and 300 K on a time scale of several milliseconds.
      Comparison of these processes in Rydberg states of H and H(2) suggests  the
      importance, in H(2), of collisional processes and of the process of blackbody
      radiation-induced predissociation.

PMID- 22613152
TI  - Supramolecular assemblies based on dative boron-nitrogen bonds.
AB  - Dative boron-nitrogen bonds were found to be a useful binding motif in structural
      supramolecular chemistry. Crystalline cages were formed using a diboronate ester
      and 2,4,6-tri(4-pyridyl)-1,3,5-triazine. These cages can act as hosts for
      electron-rich planar aromatic systems such  as triphenylene. Further, crystalline
      two-dimensional polymers were formed via dative B-N bonds between a triboronic
      ester and a ditopic pyridyl ligand. Use of an extended triboronate ester resulted
      in formation of a gel in toluene with a minimum gelation concentration of 0.5
      wt%.

PMID- 22613153
TI  - Exploring forces between individual colloidal particles with the atomic force
      microscope.
AB  - Forces between individual colloidal particles can be measured with the atomic
      force microscope (AFM), and this technique permits the study of interactions
      between surfaces across aqueous solutions in great detail. The most relevant
      forces are described by the Derjaguin, Landau, Verwey,  and Overbeek (DLVO)
      theory, and they include electrostatic double-layer and van der Waals forces. In
      symmetric systems, the electrostatic forces are repulsive and depend strongly on
      the type and concentration of the salts present, while van der Waals forces are
      always attractive. In asymmetric  systems, the electrostatic force can become
      attractive as well, even when involving neutral surfaces, while in rare
      situations van der Waals forces can become repulsive too. The enormous
      sensitivity of the double layer forces on additives present is illustrated with
      oppositely charged polyelectrolytes,  which may induce attractions or repulsions
      depending on their concentrations.

PMID- 22613154
TI  - Mass spectrometric QUAL/QUAN approaches for drug metabolism and metabolomics.
AB  - A liquid chromatography-high-resolution mass spectrometry platform was used for
      simultaneous qualitative and quantitative (QUAL/QUAN) acquisition, enabling drug
      metabolism and metabolomics investi- gations. Plasma study samples were monitored
      for three different groups of patients  at a single time-point (1 h after drug
      administration): one group received acetaminophen (APAP), one group received both
      APAP and ketorolac and one group was a control group. The quantification of APAP
      and two of its metabolites (APAP-glucuronide and APAP-cysteine) was performed on
      a fast  acquisition quadrupole-Time-Of-Flight (50-100 ms duty cycle, resolving
      power of 30,000) compatible with UHPLC time constraints. High-resolution Selected
      Reaction Monitoring was used for quantification of APAP and its metabolites from
      50-10,000 ng/mL using a 50 MUL plasma  aliquot. Average measured concentrations
      were for APAP 6,650 ng/mL vs 6,160 ng/mL, APAP-CYS concentrations were 154.2
      ng/mL vs 140.6 ng/mL and APAP-GLU concentrations 8,750 ng/mL vs 8,430 ng/mL
      between the group that received only APAP (n = 11) and the group that received
      APAP in combination  with ketorolac (n = 11). No major differences were observed
      between the two groups of patients, as it would be expected due to the differing
      metabolism pathway for both substances. For the qualitative aspect, a
      metabolomics data processing platform with biological QC samples was applied to 
      the study samples to search for unanticipated metabolites and biomarkers related
      to APAP and ketorolac metabolism. Multivariate analysis (i.e. Principle Component
      Analysis), variables grouping tools (i.e. PCVG) and high-resolution MS(/MS)
      spectra from the MS(ALL) acquisition  strategy enabled the profiling and
      characterization of circulating metabolites of APAP in plasma such as APAP
      sulfate, APAP-mercapturate as well as ketorolac.

PMID- 22613155
TI  - High spatial resolution quantitative imaging by cross-calibration using Laser
      Ablation Inductively Coupled Plasma Mass Spectrometry and Synchrotron micro-X-ray
      Fluorescence technique.
AB  - High spatial resolution, quantitative chemical imaging is of importance to
      various scientific communities, however high spatial resolution and robust
      quantification are not trivial to attain at the same time. In order to achieve
      microscopic chemical imaging with enhanced quantification  capabilities, the
      current study links the independent and complementary advantages of two micro
      analytical techniques - Synchrotron Radiation-based micro X-ray Fluorescence (SR
      microXRF) and Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA
      ICPMS). A cross-calibration approach  is established between these two techniques
      and validated by one experimental demonstration. In the presented test case, the
      diffusion pattern of trace level Cs migrating into a heterogeneous geological
      medium is imaged quantitatively with high spatial resolution. The one-dimensional
      line  scans and the two-dimensional chemical images reveal two distinct types of
      geochemical domains: calcium carbonate rich domains and clay rich domains. During
      the diffusion, Cs shows a much higher interfacial reactivity within the clay rich
      domain, and turns out to be nearly non-reactive in  the calcium carbonate
      domains. Such information obtained on the micrometer scale improves our chemical
      knowledge concerning reactive solute transport mechanism in heterogeneous media.
      Related to the chosen demonstration study, the outcome of the quantitative,
      microscopic chemical imaging contributes  to a refined safety assessment of
      potential host rock materials for deep-geological nuclear waste storage
      repositories.

PMID- 22613156
TI  - Zebrafish bioassay-guided microfractionation for the rapid in vivo identification
      of pharmacologically active natural products.
AB  - The rapid acquisition of structural and bioactivity information on natural
      products (NPs) at the sub- milligram scale is key for performing efficient
      bioactivity-guided isolations. Zebrafish offer the possibility of rapid in vivo
      bioactivity analysis of small molecules at the microgram  scale - an attractive
      feature when combined with high-resolution fractionation technologies and
      analytical methods such as UHPLC-TOF-MS and microflow NMR. Numerous biomedically
      relevant assays are now available in zebrafish, encompassing most indication
      areas. Zebrafish also provide  the possibility to screen bioactive compounds for
      potential hepato-, cardio-, and neurotoxicities at a very early stage in the drug
      discovery process. Here we describe two strategies using zebrafish bioassays for
      the high-resolution in vivo bioactivity profiling of medicinal plants, using 
      either a one-step or a two-step procedure for active compound isolation directly
      into 96-well plates. The analysis of the microfractions by microflow NMR in
      combination with UHPLC-TOF-MS of the extract enables the rapid dereplication of
      compounds and an estimation of their microgram quantities  for zebrafish
      bioassays. Both the one-step and the two-step isolation procedures enable a rapid
      estimation of the bioactive potential of NPs directly from crude extracts. In
      summary, we present an in vivo , microgram-scale NP discovery platform combining
      zebrafish bioassays with microscale  analytics to identify, isolate and evaluate
      pharmacologically active NPs.

PMID- 22613157
TI  - Indole alkaloids synthesis via a selective cyclization of aminocyclopropanes.
AB  - The continuous progress in medicinal chemistry requires more versatile synthetic
      strategies for the generation of large libraries of active compounds and their
      analogues. As a result, the research for new effective cyclization and
      cycloaddition reactions is an essential task in organic  chemistry. In 2008 we
      developed the first catalytic formal homo-Nazarov reaction starting from
      activated cyclopropanes. Herein we report the extension of the catalytic formal
      homo-Nazarov cyclization to aminocyclopropanes. Highly diastereoselective
      cyclizations were obtained via an acyliminium  intermediate generated through
      opening of the cyclopropane. An excellent control over the regioselectivity of
      either the C-C or C-N cyclization in the case of free indoles as nucleophilic
      partners was achieved. The utility of the developed methodology was demonstrated
      by the generation  of the polycyclic scaffolds of Aspidosperma and Gonioma
      natural products starting from a common intermediate. Based on this method, a
      formal total synthesis of the alkaloid aspidospermidine and the total synthesis
      of the alkaloid goniomitine are presented. Finally, the scope  and limitations of
      our methodology are discussed on an extended range of vinyl-cyclopropyl ketones
      with cyclic or acyclic carbamates, as well as ethers as donor groups on the
      cyclopropane.

PMID- 22613158
TI  - Biocompatible polymer nanoparticles for intra-cellular applications.
AB  - Polymeric styrene microspheres have a great potential at the interface of
      chemistry and biology. The progress of the synthetic development of
      multifunctional microspheres and their use as delivery agents of different
      biomolecules into cells is discussed. Their multifunctional properties open a
      wide range of applications from intracellular real-time sensors, to the use of
      microspheres as catalysts performing exogenous chemistry within cells.

PMID- 22613159
TI  - Palladium-NHC catalyzed enantioselective synthesis of fused indolines via inert
      C(sp(3))-H activation.
AB  - New sterically hindered chiral N-heterocyclic carbene (NHC) ligands were used in
      palladium catalysis to bring about a highly enantioselective C(sp(3))-H
      activation on the methylene site of a cycloalkane moiety. The intramolecular
      coupling reaction of a prochiral N-aryl-N-cycloalkyl  methyl carbamate required
      high temperatures (140-160  degrees C) and afforded highly enantioenriched trans
      2,3-fused indolines.

PMID- 22613160
TI  - Ultrafast dynamics of liquid water and ice.
AB  - In the present contribution we summarize our observations concerning the
      ultrafast non-equilibrium dynamics of water, in both the liquid and crystalline
      phase. Our experimental tool is two-dimensional infrared (2D IR) spectroscopy,
      which combines structural information on a molecular  level with femtosecond time
      resolution. In the case of liquid and supercooled water we are able to extract
      the timescales of hydrogen bonding dynamics, whereas in the ice form we can probe
      the change of the hydrogen bond properties under excitation and observe the
      influence of intermolecular  mode excitations in the crystal.

PMID- 22613161
TI  - 10. Freiburger Symposium 2011 der SCG-Division Industrielle Chemie Technology
      Progress, Success Key for our Production Sites.
AB  - This short paper presents the abstracts of the different presentations during 10.
      Freiburger Symposium 2011 der SCG-Division Industrielle Chemie: Technology
      Progress, Success key for our production sites held Thursday and Friday,
      September 29 and 30, 2011 at the Ecole d'ingenieurs et d'architectes de Fribourg
      (Switzerland).

PMID- 22613166
TI  - Isolation and characterization of an enzyme from the GreenshellTM mussel Perna
      canaliculus that hydrolyses pectenotoxins and esters of okadaic acid.
AB  - An enzyme capable of hydrolysing pectenotoxins (PTXs) and okadaic acid (OA)
      esters within the hepatopancreas of the GreenshellTM mussel Perna canaliculus was
      isolated and characterized. The enzyme was purified by sequential polyethylene
      glycol fractionation, anion exchange, hydrophobic interaction, gel filtration and
      hydroxyapatite chromatography. The enzyme was an acidic (pI ~ 4.8), monomeric, 67
      kDa, serine esterase with optimum activity at pH 8.0 and 25  degrees C. PTX2 and
      PTX1 were hydrolysed but the enzyme was inactive against PTX11, PTX6 and acid
      isomerised PTX2 and PTX11. PTX11 and PTX2b competitively inhibited PTX2
      hydrolysis. The enzyme also hydrolysed short and medium chain length (C2-C10) 4
      nitrophenyl-esters, okadaic acid C8-C10 diol esters and DTX1 7-O-palmitoyl ester
      (DTX3). MALDI-Tof MS/MS analysis showed that the enzyme had some homology with a
      juvenile hormone esterase from the Red Flour Beetle Tribolium castaneum, although
      BLAST searches of several data bases using de novo amino acid sequences failed to
      identify any homology with known proteins.

PMID- 22613167
TI  - Mouse compound muscle action potential assay: an alternative method to conduct
      the LD50 botulinum toxin type A potency test.
AB  - PURPOSE: We performed a prevalidation of the compound muscle action potential
      (CMAP) assay to determine the potency of botulinum neurotoxin type A (BoNT/A)
      with the aim of substituting for the mouse lethality test (LD50), which is used
      for quality control. METHODS: Prevalidation experiments were performed to
      demonstrate the specificity, linearity, accuracy, precision, range, limit of
      quantitation (LOQ), and robustness of the assay. For specificity, toxin detection
      ability was determined in the presence of neutralizing antibodies (0.8 and 8
      IU/mL). Linearity of this assay was determined by measuring CMAP amplitude using
      nine concentrations (n = 3) in the range of 1-100 U/mL (n = 3). Accuracy was
      assessed using five concentrations (n = 3) in the range of 4-40 U/mL.
      Intermediate precision was confirmed by analyzing individually prepared reagents
      on multiple days by one operator (n = 3). Different body weights (23-25 and 25-27
      g) and measurement times (3-5 and 5-7 min) after anesthetic induction were tested
      to assess robustness. RESULTS: This assay might have BoNT/A specificity, based on
      the CMAP amplitude recovery using a concentration of neutralizing antibodies. The
      calibration curves were linear over the range of 2-40 U/mL (R2 = 0.982). The
      accuracy of 14 determinations was within the range of 89.8-118.6% compared to the
      theoretical values among 15 determinations, except one (131.3%). Assay
      variability was acceptable with coefficients of variation of 4.3-14.4%. The range
      of quantification and the LOQ were 4-40 U/mL and 4 U/mL, respectively. Different
      body weights and measurement times after inducing anesthesia had no effect on
      CMAP amplitude. CONCLUSIONS: These results suggest that the mouse CMAP assay is
      an alternative method to the standard LD50 potency test and meets the requirement
      of the three Rs (particularly refinement and reduction).

PMID- 22613168
TI  - Post-surgical enteric fistula treatment with image-guided percutaneous injection
      of cyanoacrylic glue.

PMID- 22613169
TI  - Accuracy of high-pitch prospectively ECG-triggering CT coronary angiography for
      assessment of stenosis in 103 patients: comparison with invasive coronary
      angiography.
AB  - AIM: To investigate the accuracy of high-pitch prospectively electrocardiogram
      (ECG)-triggering low-dose, dual-source computed tomography (CT) coronary
      angiography for assessing coronary artery stenosis compared with conventional
      coronary angiography. MATERIALS AND METHODS: One hundred and three patients
      undergoing high-pitch CT coronary angiography (CTCA) and conventional coronary
      angiography (CCA) within 30 days were enrolled. The sensitivity, specificity,
      positive predictive value (PPV), and negative predictive value (NPV) of high
      pitch CTCA for detecting >50 and >70% stenosis were evaluated using CCA as the
      reference standard on a per-segment, per-vessel, and per-patient basis. Two
      experienced radiologists independently rated high-pitch CTCA images for quality
      using a four-point scale (1 = excellent, 4 = non-diagnostic) on a per-segment
      basis. The effective dose was calculated by multiplying the conversion
      coefficient of 0.028 by the dose-length product. RESULTS: The mean heart rate of
      patients was 57 +/- 6 beats/min. For detecting >50% stenosis, the sensitivity,
      specificity, PPV, and NPV of high-pitch CTCA were 89, 97, 87, and 97% on a per
      segment basis; 91, 92, 92, and 91% on a per-vessel basis; and 99, 85, 96, and 94%
      on a per-patient basis. For detecting >70% stenosis, the sensitivity,
      specificity, PPV, and NPV of high-pitch CTCA were 96, 98, 90, and 99% on a per
      segment basis. Coronary segments were rated as diagnostic in 98.6% (1355/1375) of
      cases (score 1, 72.5%; score 2, 23.1%; score 3, 3%; score 4, 1.4%). The effective
      dose of high-pitch CTCA was 1.51 +/- 0.31 mSv. CONCLUSION: High-pitch
      prospectively ECG-triggering dual-source CTCA provides good image quality and
      high diagnostic accuracy with a 1.51 mSv radiation dose.

PMID- 22613170
TI  - Frontal gray matter reduction after breast cancer chemotherapy and association
      with executive symptoms: a replication and extension study.
AB  - Cognitive changes related to cancer and its treatment have been intensely
      studied, and neuroimaging has begun to demonstrate brain correlates. In the first
      prospective longitudinal neuroimaging study of breast cancer (BC) patients we
      recently reported decreased gray matter density one month after chemotherapy
      completion, particularly in frontal regions. These findings helped confirm a
      neural basis for previously reported cognitive symptoms, which most commonly
      involve executive and memory processes in which the frontal lobes are a critical
      component of underlying neural circuitry. Here we present data from an
      independent, larger, more demographically diverse cohort that is more
      generalizable to the BC population. BC patients treated with (N=27) and without
      (N=28) chemotherapy and matched healthy controls (N=24) were scanned at baseline
      (prior to systemic treatment) and one month following chemotherapy completion (or
      yoked intervals for non-chemotherapy and control groups) and APOE-genotyped.
      Voxel-based morphometry (VBM) showed decreased frontal gray matter density after
      chemotherapy, as observed in the prior cohort, which was accompanied by self
      reported difficulties in executive functioning. Gray matter and executive symptom
      changes were not related to APOE epsilon4 status, though a somewhat greater
      percentage of BC patients who received chemotherapy were epsilon4 allele carriers
      than patients not treated with chemotherapy or healthy controls. These findings
      provide confirmatory evidence of frontal morphometric changes that may be a
      pathophysiological basis for cancer and treatment-related cognitive dysfunction.
      Further research into individual risk factors for such changes will be critical
      for development of treatment and prevention strategies.

PMID- 22613172
TI  - Impulse oscillometry may be of value in detecting early manifestations of COPD.
AB  - BACKGROUND: Spirometry is used to diagnose chronic obstructive pulmonary disease
      (COPD). The Impulse oscillometry system (IOS) allows determination of respiratory
      impedance indices, which might be of potential value in early COPD, although
      previous experience is limited. We examined pulmonary resistance and reactance
      measured by IOS in subjects with or without self-reported chronic bronchitis or
      emphysema or COPD (Q+ or Q-) and subjects with or without COPD diagnosed
      according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD)
      criteria (G+ or G-). METHODS: From a previous population-based study 450 subjects
      were examined with spirometry and IOS and answered a questionnaire on respiratory
      symptoms and diseases. RESULTS: Seventy-seven subjects were Q+, of whom 34 also
      were G+. Q+/G- subjects (n = 43) reported respiratory symptoms more frequently
      (35-40% vs 8-14%) but had higher FEV(1) (100% vs 87%) than Q-/G+ subjects (n =
      90), p < 0.05 for both comparisons. Q+ subjects had higher pulmonary resistance
      and lower pulmonary reactance than Q- subjects (p < 0.01 for all comparisons).
      The same pattern was seen both in G+ subjects ((Q+/Q-) R5 0.39/0.32, R5-R20
      0.10/0.07, X5 0.13/0.09, AX 0.55/0.27, p < 0.05 for all) and G- subjects ((Q+/Q-)
      R5 0.35/0.29, R5-R20 0.08/0.06, X5 0.10/0.08, AX 0.31/0.19 p < 0.05 for all)
      except for R20 (adjusted for gender and age). CONCLUSIONS: Self-reported chronic
      bronchitis or emphysema or COPD was associated with higher pulmonary resistance
      and lower pulmonary reactance measured by IOS, both among subjects with and
      without COPD according to GOLD criteria. IOS may have the potential to detect
      pathology associated with COPD earlier than spirometry.

PMID- 22613171
TI  - Opioid maintenance therapy restores CD4+ T cell function by normalizing
      CD4+CD25(high) regulatory T cell frequencies in heroin user.
AB  - There is an increasing body of evidence that heroin addiction is associated with
      severe alterations in immune function, which might contribute to an increased
      risk to contract infectious diseases like hepatitis B and C or HIV. However, the
      impact of heroin consumption on the CD4(+) T cell compartment is not well
      understood. Therefore, we analyzed the frequency and functional phenotype of
      CD4(+) T cells as well as immune-suppressive CD4(+)CD25(high) regulatory T cells
      (Tregs) isolated from the peripheral blood of opiate addicts currently abusing
      heroin (n=27) in comparison to healthy controls (n=25) and opiate addicts
      currently in opioid maintenance treatment (OMT; n=27). Interestingly, we detected
      a significant increase in the percentage of CD4(+)CD25(high) Tregs in the
      peripheral blood of heroin addicted patients in contrast to patients in OMT. The
      proliferative response of CD4(+) T cells upon stimulation with anti-CD3 and anti
      CD28 antibodies was significantly decreased in heroin users, but could be
      restored by depletion of CD25(high) regulatory T cells from CD4(+) T cells to
      similar values as observed from healthy controls and patients in OMT. These
      results suggest that impaired immune responses observed in heroin users are
      related to the expansion of CD4(+)CD25(high) Tregs and more importantly, can be
      restored by OMT.

PMID- 22613173
TI  - Ubiquity of synonymity: almost all large binary trees are not uniquely identified
      by their spectra or their immanantal polynomials.
AB  - BACKGROUND: There are several common ways to encode a tree as a matrix, such as
      the adjacency matrix, the Laplacian matrix (that is, the infinitesimal generator
      of the natural random walk), and the matrix of pairwise distances between leaves.
      Such representations involve a specific labeling of the vertices or at least the
      leaves, and so it is natural to attempt to identify trees by some feature of the
      associated matrices that is invariant under relabeling. An obvious candidate is
      the spectrum of eigenvalues (or, equivalently, the characteristic polynomial).
      RESULTS: We show for any of these choices of matrix that the fraction of binary
      trees with a unique spectrum goes to zero as the number of leaves goes to
      infinity. We investigate the rate of convergence of the above fraction to zero
      using numerical methods. For the adjacency and Laplacian matrices, we show that
      the a priori more informative immanantal polynomials have no greater power to
      distinguish between trees. CONCLUSION: Our results show that a generic large
      binary tree is highly unlikely to be identified uniquely by common spectral
      invariants.

PMID- 22613174
TI  - Plant-microbe interactions: novel applications for exploitation in multipurpose
      remediation technologies.
AB  - Soil remediation that revitalizes degraded or contaminated land while
      simultaneously contributing to biomass biofuel production and carbon
      sequestration is an attractive strategy to meet the food and energy requirements
      of the burgeoning world population. As a result, plant-based remediation
      approaches have been gaining in popularity. The drawbacks of phytoremediation,
      particularly those associated with low productivity and limitations to the use of
      contaminant-containing biomass, could be addressed through novel biotechnological
      approaches that harness recent advances in our understanding of chemical
      interactions between plants and microorganisms in the rhizosphere and within
      plant tissues. This opinion article highlights three promising approaches that
      provide environmental and economic benefits of bioremediation: transgenics, low
      input 'designer' plants and nanotechnology.

PMID- 22613176
TI  - Covalent modification and time-dependent inhibition of human CYP2E1 by the meta
      isomer of acetaminophen.
AB  - The hypothesis that N-acetyl-m-aminophenol (AMAP), the meta isomer of
      acetaminophen, will covalently bind to and inhibit human CYP2E1 in a time- and
      NADPH-dependent manner was investigated. Liquid chromatography/electrospray
      ionization-mass spectrometry analysis indicated that AMAP metabolites (i.e.,
      AMAP*) selectively and covalently modified CYP2E1 apoprotein in a ratio of 1.4:1
      (AMAP*/CYP2E1) in a reconstituted system. The deconvoluted spectra of CYP2E1
      apoprotein from incubations containing NADPH and AMAP displayed mass shifts of
      167.2 +/- 7.1 and 334.4 +/- 6.5 Da, suggesting the addition of one and two
      hydroxylated AMAP metabolites to CYP2E1, respectively. Mass shifts in cytochrome
      P450 reductase, cytochrome b(5), and heme from these samples were not observed.
      CYP2E1 inhibition by AMAP increased with time in the presence of NADPH; a
      reversible inhibition component was also observed. The results support a
      bioactivation process that involves formation of a hydroquinone metabolite that
      undergoes further oxidation to a quinone, which reacts with CYP2E1 nucleophilic
      residues. The data are consistent with evidence from previous studies that
      identified hydroxylated AMAP glutathione conjugates collected from mice and
      indicate that cysteine residues are the most likely sites for adduct formation.
      This study reports the first direct evidence of AMAP-derived hydroquinone
      metabolites bound to human CYP2E1.

PMID- 22613177
TI  - Antimicrobial selectivity based on zwitterionic lipids and underlying balance of
      interactions.
AB  - An important feature of antimicrobial peptides is their ability to distinguish
      pro- from eukaryotic membranes. In vitro experiments on the antimicrobial peptide
      NK-2 indicate that the discrimination between zwitterionic
      phosphatidylethanolamine lipids exposed by prokaryotes and phosphatidylcholine
      lipids exposed by eukaryotes plays an important role. The underlying mechanism is
      not understood. Here we present molecular dynamics simulations in conjunction
      with a coarse grained model and thermodynamic integration showing that NK-2 binds
      more strongly to palmitoyloleoylphosphatidylethanolamine (POPE) than to
      palmitoyloleoylphosphatidylcholine (POPC) bilayers. Finite size effects on the
      relative free energy have been corrected for with a method that may also be
      useful in future studies of the affinities of macromolecules for lipid membranes.
      Our results support the previous hypothesis that the stronger binding to PE
      compared to PC arises from a better accessibility of the phosphates of the lipids
      to the cationic peptide in a sense that a similar number of peptide-lipid salt
      bridges requires to break more favorable electrostatic headgroup-headgroup
      interactions for PC relative to PE. The transfer of NK-2 from POPC to POPE is
      found to lead to a decrease in electrostatic peptide-lipid but an increase in
      lipid-lipid and ion-lipid interactions, correlating with a dehydration of the
      lipids and the ions but an increased hydration of the peptide. The increase in
      affinity of NK-2 for POPE compared to POPC hence arises from a complex interplay
      of competing interactions. This work opens the perspective to study how the
      affinity of antimicrobial peptides changes with amino acid sequence and lipid
      composition.

PMID- 22613178
TI  - Gap junction proteins on the move: connexins, the cytoskeleton and migration.
AB  - Connexin43 (Cx43) has roles in cell-cell communication as well as channel
      independent roles in regulating motility and migration. Loss of function
      approaches to decrease Cx43 protein levels in neural cells result in reduced
      migration of neurons during cortical development in mice and impaired glioma
      tumor cell migration. In other cell types, correlations between Cx43 expression
      and cell morphology, adhesion, motility and migration have been noted. In this
      review we will discuss the common themes that have been revealed by a detailed
      comparison of the published results of neuronal cells with that of other cell
      types. In brief, these comparisons clearly show differences in the stability and
      directionality of protrusions, polarity of movement, and migration, depending on
      whether a) residual Cx43 levels remain after siRNA or shRNA knockdown, b) Cx43
      protein levels are not detectable as in cells from Cx43(-/-) knockout mice or in
      cells that normally have no endogenous Cx43 expression, c) gain-of-function
      approaches are used to express Cx43 in cells that have no endogenous Cx43 and, d)
      Cx43 is over-expressed in cells that already have low endogenous Cx43 protein
      levels. What is clear from our comparisons is that Cx43 expression influences the
      adhesiveness of cells and the directionality of cellular processes. These
      observations are discussed in light of the ability of cells to rearrange their
      cytoskeleton and move in an organized manner. This article is part of a Special
      Issue entitled: The Communicating junctions, roles and dysfunctions.

PMID- 22613179
TI  - Elevated plasma levels of heparin-binding protein in intensive care unit patients
      with severe sepsis and septic shock.
AB  - INTRODUCTION: Rapid detection of, and optimized treatment for, severe sepsis and
      septic shock is crucial for successful outcome. Heparin-binding protein (HBP), a
      potent inducer of increased vascular permeability, is a potentially useful
      biomarker for predicting outcome in patients with severe infections. Our aim was
      to study the systemic release and dynamics of HBP in the plasma of patients with
      severe sepsis and septic shock in the ICU. METHODS: A prospective study was
      conducted of two patient cohorts treated in the ICU at Karolinska University
      Hospital Huddinge in Sweden. A total of 179 patients was included, of whom 151
      had sepsis (126 with septic shock and 25 patients with severe sepsis) and 28 a
      non-septic critical condition. Blood samples were collected at five time points
      during six days after admission. RESULTS: HBP levels were significantly higher in
      the sepsis group as compared to the control group. At admission to the ICU, a
      plasma HBP concentration of >= 15 ng/mL and/or a HBP (ng/mL)/white blood cell
      count (109/L) ratio of >2 was found in 87.2% and 50.0% of critically ill patients
      with sepsis and non-septic illness, respectively. A lactate level of >2.5 mmol/L
      was detected in 64.9% and 56.0% of the same patient groups. Both in the sepsis
      group (n = 151) and in the whole group (n = 179), plasma HBP concentrations at
      admission and in the last measured sample within the 144 hour study period were
      significantly higher among 28-day non-survivors as compared to survivors and in
      the sepsis group, an elevated HBP-level at baseline was associated with an
      increased case-fatality rate at 28 days. CONCLUSIONS: Plasma HBP levels were
      significantly higher in patients with severe sepsis or septic shock compared to
      patients with a non-septic illness in the ICU. HBP was associated with severity
      of disease and an elevated HBP at admission was associated with an increased risk
      of death. HBP that rises over time may identify patients with a deteriorating
      prognosis. Thus, repeated HBP measurement in the ICU may help monitor treatment
      and predict outcome in patients with severe infections.

PMID- 22613181
TI  - Cardiac myxolipoma in a child: diagnosis and surgical management.
AB  - We present a case of a rare tumor, a myxolipoma, appearing in a 5-year-old child,
      along with the imaging evaluation and surgical management. The natural history is
      expected to be that of a benign lesion, but the rarity precludes large studies.

PMID- 22613180
TI  - Increased neuron specific enolase expression by urothelial cells exposed to or
      malignantly transformed by exposure to Cd2+ or As3+.
AB  - Neuron specific enolase (ENO2, gamma-enolase) is a biomarker used to help
      identify neuroendocrine differentiation in tumors. This laboratory has shown that
      ENO2 might be a biomarker for exposure to cadmium and arsenite. In this study
      these observations are extended to the urothelial cell, where environmental
      exposures are strongly linked to urothelial cancer. The UROtsa urothelial cell
      line and its Cd2+- and As3+-transformed counterparts were used as the model.
      Acute exposure of the UROtsa cells to both As3+- and Cd2+-caused significant
      increases in ENO2 expression. Treatment with the histone deacetlyase inhibitor
      was also shown to significantly increase the expression of ENO2 mRNA. The
      expression of ENO2 was significantly elevated in the Cd2+- and As3+-transformed
      UROtsa cells and tumor transplants. In contrast, ENO1, was unaffected by exposure
      to As3+ or Cd2+. Immunofluorescence showed ENO2 associated with both the nucleus
      and cytoplasm and cytoplasmic ENO2 co-localized with ENO1. The findings extend
      the evidence suggesting a link between As3+ and Cd2+ exposure and neuroendocrine
      differentiation in tumors. The results suggest that ENO2 might be a biomarker of
      human exposure to Cd2+ and As3+ that operates through histone modification.

PMID- 22613182
TI  - Targeting problematic users of illicit drugs with Internet-based screening and
      brief intervention: a randomized controlled trial.
AB  - BACKGROUND: The aim of this study is to investigate the effects of an Internet
      based screening and brief intervention (SBI) site for problematic alcohol and
      drug use among illicit drug users. METHOD: Individuals searching for information
      about alcohol or drugs online who scored over 0 on the drug use disorders
      identification test (DUDIT) and were 15 years or older were recruited for this
      trial and randomized into one group receiving Internet-based screening and brief
      intervention via eScreen.se (n=101) or one assessment-only control group (n=101).
      Both groups were screened at baseline and followed up at 3 and 6 months. The
      primary outcome measure was the DUDIT-C score and secondary outcome measures were
      DUDIT, AUDIT-C (alcohol use disorders identification test-C) and AUDIT scores.
      Additional outcomes included the proportion of drug abstainers and those who made
      a clinically significant change in their alcohol and drug use. Four statistical
      models of analysis were used to conservatively assess results. RESULTS: A
      significant decrease in DUDIT-C scores at the 3-month follow-up occurred in both
      groups. Three out of four statistical models showed a larger decrease in the
      DUDIT score in the intervention group than in the control group (p=0.006;
      p=0.046; p=0.001). Two models showed a continued decrease in AUDIT-C and AUDIT
      scores also at the 6-month follow-up in the intervention group but not in the
      control group. No additional differences occurred. CONCLUSIONS: The results are
      inconclusive but provide some evidence that SBI sites such as eScreen.se could be
      effective for short-term reductions of problematic substance use.

PMID- 22613183
TI  - Robotic-assisted laparoscopic vesiculectomy for lower urinary tract obstruction
      by a large seminal vesicle cyst.
AB  - INTRODUCTION: Seminal vesicle (SV) cysts are rare, benign lesions. Most of them
      are congenital in origin and are usually diagnosed incidentally due to extensive
      imaging. When symptomatic, surgical excision is recommended. PRESENTATION OF
      CASE: We describe the case of a 17.2cm seminal vesicle cyst removed using a
      transperitoneal, robotic-assisted laparoscopic approach in a 45-year old male
      with lower urinary tract symptoms and no other genitourinary abnormality.
      DISCUSSION: Laparoscopic excision of seminal vesicle cysts is a minimal invasive
      alternative to the open technique with single-center studies reporting high
      success rates. With the advent of the robotic platform, urologists have shifted
      to this approach especially for confined anatomical spaces such as the pelvis. To
      our knowledge this is the largest seminal vesicle cyst described in the
      literature that has been managed by minimally invasive surgery. CONCLUSION: With
      the advantage of combined 3D vision and wristed instrumentation, excision of
      large seminal vesicle cysts by robotic assisted laparoscopic approach is
      feasible, safe and regarded as a natural continuity of conventional laparoscopy.
      Previous experience in Robotic assisted laparoscopic prostatectomy (RALP)
      especially in the posterior dissection technique is recommended.

PMID- 22613184
TI  - The impact of heat treatment on interactions of contact-poled biphasic calcium
      phosphates with proteins and cells.
AB  - A number of studies have reported improved bone integration for calcium phosphate
      based materials electrically "poled" by an external electric field prior to
      implantation. In our study we investigated the effects of electrical polarization
      of a biphasic ceramic composed of 80% hydroxyapatite and 20% beta-tricalcium
      phosphate. As contact poling involves elevated temperatures as a prerequisite for
      inducing charge, we used two reference types: samples without any heat treatment
      and poling, and samples with no poling but heat treatment identical to that of
      the poled samples. All heat-treated samples (poled or unpoled) showed an improved
      wettability, which was attributed to a reduced hydrocarbon contamination. Heat
      treatment alone provoked an accelerated spreading of osteoblast-like cells,
      whereas on poled samples a retarded cell spreading was observed. While
      proliferation and several differentiation markers were not influenced by either
      heat treatment or poling, the release of proinflammatory cytokines interleukin-6
      and -8 was significantly reduced for all heat-treated samples, irrespective of
      additional electrical poling. The study demonstrated that the behaviour of cells
      in contact with poled biphasic ceramics was influenced by two parameters: heating
      and charge. Our data revealed that heating of the calcium phosphate ceramics had
      a much more pronounced effect on cell behaviour than charge.

PMID- 22613185
TI  - A theoretical framework informing research about the role of stress in the
      pathophysiology of bipolar disorder.
AB  - BACKGROUND: The staggering illness burden associated with Bipolar Disorder (BD)
      invites the need for primary prevention strategies. Before preventative
      strategies can be considered in individuals during a pre-symptomatic period
      (i.e., at risk), unraveling the mechanistic steps wherein external stress is
      transduced and interacts with genetic vulnerability in the early stages of BD
      will be a critical conceptual necessity. METHODS: Herein we comprehensively
      review extant studies reporting on stress and bipolar disorder. The overarching
      aim is to propose a conceptual framework to inform research about the role of
      stress in the pathophysiology of BD. Computerized databases i.e. PubMed,
      PsychInfo, Cochrane Library and Scielo were searched using the following terms:
      "bipolar disorder" cross-referenced with "stress", "general reaction to stress",
      "resilience", "resistance", "recovery" "stress-diathesis", "allostasis", and
      "hormesis". RESULTS: Data from literature indicate the existence of some
      theoretical models to understand the influence of stress in the pathophysiology
      of BD, including classical stress-diathesis model and new models such as
      allostasis and hormesis. In addition, molecular mechanisms involved in stress
      adaptation (resistance, resilience and recovery) can also be translated in
      research strategies to investigate the impact of stress in the pathophysiology of
      BD. LIMITATIONS: Most studies are retrospective and/or cross sectional, do not
      consider the period of development, assess brain function with only one or few
      methodologies, and use animal models which are not always similar to human
      phenotypes. CONCLUSION: The interaction between stress and brain development is
      dynamic and complex. In this article we proposed a theoretical model for
      investigation about the role of stress in the pathophysiology of BD, based on the
      different kinds of stress adaptation response and their putative neurobiological
      underpinnings.

PMID- 22613187
TI  - Frequency and risk factors for HIV-associated neurocognitive disorder and
      depression in older individuals with HIV in northeastern Brazil.
AB  - BACKGROUND: The study was undertaken to describe the frequency of HIV-associated
      neurocognitive disorders (HAND) and depressive symptoms in an older population
      with human immunodeficiency virus (HIV). METHODS: A cross-sectional analysis of
      patients aged 50 years or older infected with HIV was carried out in an
      outpatient setting in Brazil from March to November 2008. Patients selected were
      submitted to cognitive evaluation using the Mini-Mental State Examination and
      International HIV Dementia Scale, and also to functional and depression
      evaluations. RESULTS: Among the 52 patients evaluated, the frequency of
      neurocognitive disorder was 36.5%, while for dementia the frequency was 13.5%. No
      risk factors were identified. Among the patients with cognitive impairment, 73.7%
      had cortical impairment. The frequency of depressive symptoms was of 34.6%. The
      female gender was identified as a risk factor (p = 0.018) and patients with
      depressive symptoms had greater functional impairment (p < 0.001). CONCLUSION:
      HAND and depressive symptoms are common in an older population. Patients with
      cognitive impairment achieved lower scores on the cortical assessment scales.
      Depressive symptoms are a stronger factor for functional impairment.

PMID- 22613186
TI  - Neurocognitive dysfunction in strategic and non-strategic gamblers.
AB  - OBJECTIVE: It has been theorized that there may be subtypes of pathological
      gambling, particularly in relation to the main type of gambling activities
      undertaken. Whether or not putative pathological gambling subtypes differ in
      terms of their clinical and cognitive profiles has received little attention.
      METHOD: Subjects meeting DSM-IV criteria for pathological gambling were grouped
      into two categories of preferred forms of gambling - strategic (e.g., cards,
      dice, sports betting, stock market) and non-strategic (e.g., slots, video poker,
      pull tabs). Groups were compared on clinical characteristics (gambling severity,
      and time and money spent gambling), psychiatric comorbidity, and neurocognitive
      tests assessing motor impulsivity and cognitive flexibility. RESULTS: Seventy
      seven subjects were included in this sample (45.5% females; mean age: 42.7+/
      14.9) which consisted of the following groups: strategic (n=22; 28.6%) and non
      strategic (n=55; 71.4%). Non-strategic gamblers were significantly more likely to
      be older, female, and divorced. Money spent gambling did not differ significantly
      between groups although one measure of gambling severity reflected more severe
      problems for strategic gamblers. Strategic and non-strategic gamblers did not
      differ in terms of cognitive function; both groups showed impairments in
      cognitive flexibility and inhibitory control relative to matched healthy
      volunteers. CONCLUSION: These preliminary results suggest that preferred form of
      gambling may be associated with specific clinical characteristics but are not
      dissociable in terms of cognitive inflexibility and motor impulsivity.

PMID- 22613188
TI  - Giant cell fibroblastoma with translocation t(17;22) arising in a post-surgical
      scar in a 40-year-old woman.

PMID- 22613189
TI  - Externalization of phosphatidylserine from inner to outer layer may alter the
      effect of plant sterols on human erythrocyte membrane - the Langmuir monolayer
      studies.
AB  - One of the factors, which can strongly modify the cell membrane composition, is
      disordering in membrane asymmetry, resulting from redistribution of lipids from
      inner to outer layer. Such a disturbance may affect the behavior of various
      biologically active compounds incorporating into membranes. In this contribution,
      the relationship between the amounts of phosphatidylserine (PS) in the model
      outer layer of human erythrocyte (RBC) membrane and the effect induced by a plant
      sterol (beta-sitosterol) was verified. The experiments were performed on
      multicomponent Langmuir films imitating red blood cell (RBC) membrane, differing
      in the contents of PS (0%; 5% and 10%) into which the plant sterol was
      incorporated in various concentrations. The analysis of experimental results
      (surface pressure-area isotherms complemented with Brewster Angle Microscopy
      (BAM) proved that the presence of phosphatidylserine molecules, depending on
      their contents in the mixed monolayer mimicking RBC membrane, changes its
      properties and exerts influence on the effect of plant sterol on the model
      system. The addition of phytosterol into the monolayer that lacks or contains
      only 5% of PS was found to be of rather weak effect on the properties of the
      system. However, in the case of the model membrane containing the increased
      amount (10%) of PS, the incorporation of plant sterol strongly affects the
      interactions between molecules and caused thermodynamic destabilization of the
      monolayer imitating RBC membrane. These results allow one to suggest that
      externalization of phosphatidyserine to the outer membrane leaflet may
      differentiate the effect of plant sterols on cell membranes of various origins.

PMID- 22613190
TI  - Chemoimmunotherapy with bendamustine hydrochloride and alemtuzumab demonstrates
      synergism in T-prolymphocytic leukemia.

PMID- 22613191
TI  - Combined chemotherapy and ALA-based photodynamic therapy in leukemic murine
      cells.
AB  - The effects of combined administration of doxorubicin (DOX) and vincristine
      (VCR), with 5-aminolevulinic acid photodynamic treatment (ALA-PDT), were analyzed
      in sensitive murine leukemic cell lines (LBR-) and DOX and VCR chemoresistant LBR
      D160 and LBR-V160 cell lines. Low doses of DOX and VCR increased anti-cancer
      effect of ALA-PDT in LBR-cells. Decrease in cell survival was higher when the
      combination VCR+ALA-PDT was used compared to DOX+ALA-PDT. Resistant cell lines
      LBR-D160 and LBR-V160 were sensitive to ALA-PDT; however, no changes occured when
      combining therapies. Thus, ALA-PDT can overcome drug resistance and is a good
      candidate for using treating multidrug resistant (MDR) cells.

PMID- 22613193
TI  - The discriminability of local cues determines the strength of holistic face
      processing.
AB  - Face perception is thought to result from the dynamic interplay between holistic
      and featural modes of processing. What determines the engagement of each mode is
      currently unknown. Here, we investigated whether the discriminability of local
      feature cues is a critical determinant of holistic/featural processing
      engagement. We estimated the strength of holistic processing based on observers'
      failure to discriminate target features independently of the context of
      distracter features in a congruency paradigm. Feature discriminability was
      manipulated by varying the dissimilarity of target features parametrically, using
      morphing. We observed that the size of the congruency effect decayed
      monotonically as a function of the dissimilarity of the target features. In other
      words, the more similar the target features the stronger the holistic processing.
      A correlation analysis confirmed that local feature discriminability reliably
      predicted holistic engagement at upright orientation. In contrast, when a clear
      local feature difference was detected, perceptual contamination by the other
      surrounding features was prevented. This evidence firmly suggests that the
      interplay between holistic/featural processing depends on the discriminability of
      the signal provided at the local featural level.

PMID- 22613192
TI  - Light-scattering sensor for real-time identification of Vibrio parahaemolyticus,
      Vibrio vulnificus and Vibrio cholerae colonies on solid agar plate.
AB  - The three most common pathogenic species of Vibrio, Vibrio cholerae, Vibrio
      parahaemolyticus and Vibrio vulnificus, are of major concerns due to increased
      incidence of water- and seafood-related outbreaks and illness worldwide. Current
      methods are lengthy and require biochemical and molecular confirmation. A novel
      label-free forward light-scattering sensor was developed to detect and identify
      colonies of these three pathogens in real time in the presence of other vibrios
      in food or water samples. Vibrio colonies grown on agar plates were illuminated
      by a 635 nm laser beam and scatter-image signatures were acquired using a CCD
      (charge-coupled device) camera in an automated BARDOT (BActerial Rapid Detection
      using Optical light-scattering Technology) system. Although a limited number of
      Vibrio species was tested, each produced a unique light-scattering signature that
      is consistent from colony to colony. Subsequently a pattern recognition system
      analysing the collected light-scatter information provided classification in 1-2
      min with an accuracy of 99%. The light-scattering signatures were unaffected by
      subjecting the bacteria to physiological stressors: osmotic imbalance, acid, heat
      and recovery from a viable but non-culturable state. Furthermore, employing a
      standard sample enrichment in alkaline peptone water for 6 h followed by plating
      on selective thiosulphate citrate bile salts sucrose agar at 30 degrees C for ~
      12 h, the light-scattering sensor successfully detected V. cholerae, V.
      parahaemolyticus and V. vulnificus present in oyster or water samples in 18 h
      even in the presence of other vibrios or other bacteria, indicating the
      suitability of the sensor as a powerful screening tool for pathogens on agar
      plates.

PMID- 22613194
TI  - [Reflections on the previous instructions document].

PMID- 22613195
TI  - [Mycobacterium tuberculosis as etiological agent of adult infectious
      spondylodiscitis].

PMID- 22613196
TI  - [Purulent pericardial tamponade secondary to hepatic abscess caused by
      Streptococcus milleri].

PMID- 22613197
TI  - Prophylactic use of helmet CPAP after pulmonary lobectomy: a prospective
      randomized controlled study.
AB  - BACKGROUND: Patients undergoing pulmonary lobectomy carry a high risk of
      respiratory complications after surgery. The postoperative prophylactic treatment
      with helmet CPAP may prevent postoperative acute respiratory failure and improve
      the P(aO(2))/F(IO(2)). METHODS: We randomly allocated 50 subjects to receive
      continuous oxygen therapy (air-entrainment mask, F(IO(2)) 0.4) or 2 cycles of
      helmet CPAP for 120 min, alternating with analog oxygen therapy for 4 hours.
      Blood gas values were collected at admission to ICU, after 1, 3,  7, 9, 24 hours,
      and then in the thoracic ward after 48 hours and one week after surgery. We
      investigated the incidence of postoperative complications, mortality, and length
      of hospital stay. RESULTS: At the end of the second helmet CPAP treatment, the
      subjects had a significantly higher P(aO(2))/F(IO(2)),  compared with the control
      group (366 +/- 106 mm Hg vs 259 +/- 60 mm Hg, P = .004), but the improvement in
      oxygenation did not continue beyond 24 hours. The postoperative preventive helmet
      CPAP treatment was associated with a significantly shorter hospital stay, in
      comparison  to standard treatment (7 +/- 4 d and 8 +/- 13 d, respectively, P =
      .042). The number of minor or major postoperative complications was similar
      between the 2 groups. No difference in ICU readmission or mortality was observed.
      CONCLUSIONS: The prophylactic use of helmet CPAP  improved the P(aO(2))/F(IO(2)),
      but the oxygenation benefit was not lasting. In our study, helmet CPAP was a
      secure and well tolerated method in subjects who underwent pulmonary lobectomy.
      It might be safely applied whenever necessary.

PMID- 22613198
TI  - Reform by subtraction: the path of denunciation of international drug treaties
      and reaccession with reservations.
AB  - Almost all countries are parties to the international drug conventions of 1961,
      1971 and 1988. These strongly bind parties with respect to their domestic
      regulation of controlled substances, including requirements that possession,
      growing or use be a criminal offense and that any regulated market in the
      substances be limited to use only for medical or scientific purposes. Even where
      countries have argued they have "wiggle room", reform within the bounds of the
      conventions has often resulted in "net-widening" which nullifies the intent of
      the reform. Among the options for effective reform, probably the most immediately
      viable is the route of denunciation and reaccession with reservations--the route
      which Bolivia has now taken in order to legalise a regulated domestic market in
      coca leaves for chewing. The paper considers the existing record of reservations
      (by more than 30 parties to each of the conventions). Also discussed are the
      options for response to the reservations by other parties, which vary between the
      treaties, and how pursuing the option of denunciation and reaccession with
      reservation might potentially play out.

PMID- 22613199
TI  - Characterisation of the endocannabinoid system in rat haemochorial placenta.
AB  - Trophoblast cells that comprise the placenta play a crucial role in the complex
      cross-talk between fetus and maternal tissues. Although anandamide and 2
      arachidonoylglycerol, the best studied endocannabinoids, affect trophoblast
      attachment and outgrowth, the functional significance of the endocannabinoid
      system in the development of placenta has not been established. We investigated
      the correlation between endocannabinoid levels and the pattern of expression of
      the receptors and metabolic enzymes of the endocannabinoid system during rat
      placental development. Here, we showed that all the endocannabinoid machinery is
      dynamically expressed in the functionally distinct basal and labyrinth zones of
      the rat placenta. Indeed, endocannabinoid levels are shown to increase with the
      progression of pregnancy. Together, these data support a role for the
      endocannabinoid system in normal placental function and evidence for a potential
      novel cellular target for the deleterious action of cannabis-derived compounds
      during the second half of pregnancy.

PMID- 22613200
TI  - Comparison of polyfluoroalkyl compound concentrations in maternal serum and
      amniotic fluid: a pilot study.
AB  - The extent to which polyfluoroalkyl compounds (PFCs) are detectable in amniotic
      fluid is unknown. Using paired samples from 28 women, we compared the
      concentration of 8 PFCs measured in serum, the standard matrix for assessing
      human exposure, amniotic fluid from routine amniocentesis, and urine.
      Perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorooctane sulfonate
      (PFOS), and perfluorohexane sulfonate (PFHxS) were detected in all maternal serum
      samples. The number of amniotic fluid samples with detectable concentrations
      differed by PFC (PFOA n=24; PFNA n=10; PFOS n=9; PFHxS n=4). The correlation
      coefficient between maternal serum and amniotic PFC levels varied considerably by
      PFC (PFOA rho=0.64, p<0.001; PFNA rho=0.05, p=0.9; PFOS rho=0.76, p=0.01; PFHxS
      rho=0.80, p=0.2). Using linear regression, PFOA appeared to be commonly detected
      in amniotic fluid if the serum concentration exceeded approximately 1.5 ng/mL
      whereas PFOS was rarely detected in amniotic fluid until the serum concentration
      was about 5.5 ng/mL. No PFCs were detected in urine.

PMID- 22613201
TI  - Guaiacol production from ferulic acid, vanillin and vanillic acid by
      Alicyclobacillus acidoterrestris.
AB  - Alicyclobacilli are thermophilic, acidophilic bacteria (TAB) that spoil fruit
      juice products by producing guaiacol. It is currently believed that guaiacol is
      formed by Alicyclobacillus in fruit juices as a product of ferulic acid
      metabolism. The aim of this study was to identify the precursors that can be
      metabolised by Alicyclobacillus acidoterrestris to produce guaiacol and to
      evaluate the pathway of guaiacol production. A. acidoterrestris FB2 was incubated
      at 45 degrees C for 7days in Bacillus acidoterrestris (BAT) broth supplemented
      with ferulic acid, vanillin or vanillic acid, respectively. The samples were
      analysed every day to determine the cell concentration, the supplement
      concentration using high performance liquid chromatography with UV-diode array
      detection (HPLC-DAD) and the guaiacol concentration, using both the peroxidase
      enzyme colourimetric assay (PECA) and HPLC-DAD. The cell concentration of A.
      acidoterrestris FB2 during the 7days in all samples were above the critical cell
      concentration of 10(5)cfu/mL reportedly required for guaiacol production. The
      guaiacol produced by A. acidoterrestris FB2 increased with an increase in
      vanillin or vanillic acid concentration and a metabolic pathway of A.
      acidoterrestris FB2 directly from vanillin to guaiacol was established. The high
      concentration of vanillic acid (1000mg/L) resulted in an initial inhibitory
      effect on the cells, but the cell concentration increased after day 2. Guaiacol
      production did not occur in the absence of either a precursor or A.
      acidoterrestris FB2 and guaiacol was not produced by A. acidoterrestris FB2 in
      the samples supplemented with ferulic acid. The presence of Alicyclobacillus spp.
      that has the ability to produce guaiacol, as well as the substrates vanillin or
      vanillic acid is prerequisite for production of guaiacol.

PMID- 22613203
TI  - AIRE-induced apoptosis is associated with nuclear translocation of stress sensor
      protein GAPDH.
AB  - AIRE (Autoimmune Regulator) has a central role in the transcriptional regulation
      of self-antigens in medullary thymic epithelial cells, which is necessary for
      negative selection of autoreactive T cells. Recent data have shown that AIRE can
      also induce apoptosis, which may be linked to cross-presentation of these self
      antigens. Here we studied AIRE-induced apoptosis using AIRE over-expression in a
      thymic epithelial cell line as well as doxycycline-inducible HEK293 cells. We
      show that the HSR/CARD domain in AIRE together with a nuclear localization signal
      is sufficient to induce apoptosis. In the nuclei of AIRE-positive cells, we also
      found an increased accumulation of a glycolytic enzyme, glyceraldehyde-3
      phosphate (GAPDH) reflecting cellular stress and apoptosis. Additionally, AIRE
      induced apoptosis was inhibited with an anti-apoptotic agent deprenyl that blocks
      GAPDH nitrosylation and nuclear translocation. We propose that the AIRE-induced
      apoptosis pathway is associated with GAPDH nuclear translocation and induction of
      NO-induced cellular stress in AIRE-expressing cells.

PMID- 22613204
TI  - Complex I generated, mitochondrial matrix-directed superoxide is released from
      the mitochondria through voltage dependent anion channels.
AB  - Mitochondrial complex I has previously been shown to release superoxide
      exclusively towards the mitochondrial matrix, whereas complex III releases
      superoxide to both the matrix and the cytosol. Superoxide produced at complex III
      has been shown to exit the mitochondria through voltage dependent anion channels
      (VDAC). To test whether complex I-derived, mitochondrial matrix-directed
      superoxide can be released to the cytosol, we measured superoxide generation in
      mitochondria isolated from wild type and from mice genetically altered to be
      deficient in MnSOD activity (TnIFastCreSod2(fl/fl)). Under experimental
      conditions that produce superoxide primarily by complex I (glutamate/malate plus
      rotenone, GM+R), MnSOD-deficient mitochondria release ~4-fold more superoxide
      than mitochondria isolated from wild type mice. Exogenous CuZnSOD completely
      abolished the EPR-derived GM+R signal in mitochondria isolated from both
      genotypes, evidence that confirms mitochondrial superoxide release. Addition of
      the VDAC inhibitor DIDS significantly reduced mitochondrial superoxide release
      (~75%) in mitochondria from either genotype respiring on GM+R. Conversely,
      inhibition of potential inner membrane sites of superoxide exit, including the
      matrix face of the mitochondrial permeability transition pore and the inner
      membrane anion channel did not reduce mitochondrial superoxide release in the
      presence of GM+R in mitochondria isolated from either genotype. These data
      support the concept that complex I-derived mitochondrial superoxide release does
      indeed occur and that the majority of this release occurs through VDACs.

PMID- 22613202
TI  - Complicated intra-abdominal infections in Europe: preliminary data from the first
      three months of the CIAO Study.
AB  - The CIAO Study is a multicenter observational study currently underway in 66
      European medical institutions over the course of a six-month study period
      (January-June 2012).This preliminary report overviews the findings of the first
      half of the study, which includes all data from the first three months of the six
      month study period.Patients with either community-acquired or healthcare
      associated complicated intra-abdominal infections (IAIs) were included in the
      study.912 patients with a mean age of 54.4 years (range 4-98) were enrolled in
      the study during the first three-month period. 47.7% of the patients were women
      and 52.3% were men. Among these patients, 83.3% were affected by community
      acquired IAIs while the remaining 16.7% presented with healthcare-associated
      infections. Intraperitoneal specimens were collected from 64.2% of the enrolled
      patients, and from these samples, 825 microorganisms were collectively
      identified.The overall mortality rate was 6.4% (58/912). According to univariate
      statistical analysis of the data, critical clinical condition of the patient upon
      hospital admission (defined by severe sepsis and septic shock) as well as
      healthcare-associated infections, non-appendicular origin, generalized
      peritonitis, and serious comorbidities such as malignancy and severe
      cardiovascular disease were all significant risk factors for patient
      mortality.White Blood Cell counts (WBCs) greater than 12,000 or less than 4,000
      and core body temperatures exceeding 38 degrees C or less than 36 degrees C by
      the third post-operative day were statistically significant indicators of patient
      mortality.

PMID- 22613205
TI  - Genetic analysis of SIRT1 gene promoter in sporadic Parkinson's disease.
AB  - Parkinson's disease (PD) is one of the most common neurodegenerative diseases. To
      date, genetic causes and underlying molecular mechanisms for sporadic PD remain
      largely unknown. Sirtuis are highly conserved NAD-dependent class III
      deacetylases. SIRT1, the closest to yeast Sir2, has deacetylase activity and ADP
      ribosyltransferase activity. SIRT1 gene has been connected to many cellular
      processes and implicated in human diseases, such as obesity, type 2 diabetes,
      cancer and neurodegenerative diseases. Studies in animal model have also
      associated SIRT1 with aggregation of alpha-synuclein, a critical protein in the
      PD pathogenesis. We hypothesized that the genetic variants within the regulatory
      regions of SIRT1 gene that repress its gene expression, rather than mutations in
      its coding region that abolish SIRT1 function, may contribute to PD as a risk
      factor. In this study, we genetically analyzed the promoter region of SIRT1 gene
      in sporadic PD patients and ethic-matched healthy controls. Three novel
      heterozygous sequence variants, g.69644133C>G, g.69644213G>A and g.69644351G>A,
      were identified in PD patients, but in none of controls, which may alter the
      transcriptional activities of SIRT1 gene promoter, resulting in reduced SIRT1
      levels. One novel heterozygous variant, g.69644219G>A, linked with single
      nucleotide polymorphism - g.69644217A>C (rs932658), was only found in one
      control, which may have no functional activity. Therefore, our results suggested
      that genetic variants within the SIRT1 gene promoter may repress SIRT1 gene
      expression, contributing to PD as a risk factor.

PMID- 22613206
TI  - Current therapies for cardiac allograft vasculopathy in children.
AB  - Heart transplantation is an accepted therapy for end-stage heart disease in
      children and adults. Over the past 25 years, the perioperative and 1-year
      mortality has steadily improved, leading to an increased focus on midterm and
      late-term complications. Cardiac allograft vasculopathy (CAV) is the leading
      cause of late graft loss in children. The prevalence of disease increases
      steadily after transplantation from 5% at 2 years to 35% by 10 years according to
      multiple database analyses. Allograft vasculopathy is the end point of a complex
      interaction of stimuli including chronic rejection, endothelial dysfunction,
      infection, and traditional cardiac risk factors. While an increased understanding
      of risks associated to CAV has led to more aggressive surveillance approaches,
      the rates of CAV remain high and outcomes after diagnosis of CAV are very poor
      with up to 50% of children suffering graft loss or death within 2 years of
      diagnosis. In an attempt to combat the development and progression of CAV,
      multiple medical and interventional strategies have been utilized. Pharmacologic
      approaches have focused on the use of various immunosuppressants and adjuvant
      medications to combat inflammation and immune mediated graft injury. While
      randomized controlled trials are rare in pediatric heart transplant cohorts,
      sufficient adult data have been developed in both controlled and observational
      trials to provide a framework for the prevention and management of patients with
      CAV. However, none of these interventions have been shown to be effective in
      significantly prolonging graft survival and retransplantation remains the only
      reliable therapy for severe CAV.

PMID- 22613207
TI  - Smart design of intratumoral thermosensitive beta-lapachone hydrogels by
      Artificial Neural Networks.
AB  - This study presents Artificial Neural Networks (ANN) as a tool for designing
      injectable intratumoral formulations of the anticancer drug beta-lapachone. This
      methodology permits insight into the interactions between variables and
      determines the design space of the formulation without the restrictions of an
      experimental design. An ANN model for two critical parameters of the
      formulations; the amount of solubilized drug and gel temperature was developed
      and validated. The model allowed an understanding of interactions between
      ingredients in the formulation and the fundamental phenomena as the formation of
      polypseudorotaxanes to be detected and quantified.

PMID- 22613208
TI  - Cell-penetrating peptide mimicking polymer-based combined delivery of paclitaxel
      and siRNA for enhanced tumor growth suppression.
AB  - Cancer chemotherapy is often limited, since more than one molecule is usually
      involved with the cancer pathogenesis. A combination of therapeutic drugs would
      be a promising approach to overcome the complexity of tumors. In this study, a
      conjugate (DA3) of deoxycholic acid and low molecular weight polyethylenimine
      (PEI 1.8 kDa), which has a property that mimics that of cell penetrating peptides
      (CPPs), was used for simultaneous delivery of an anticancer drug and siRNA. When
      complexed with siRNA, DA3 showed significantly higher target gene silencing
      efficiency than PEI 25 kDa. The gene silencing efficiency of DA3 was maintained
      even in the presence of endocytosis inhibitors, suggesting that the polymeric
      carrier can mediate an endocytosis-independent macromolecular transduction
      similar to CPPs. The capability of forming a micelle-like core-shell structure
      enables the conjugates to encapsulate and dissolve paclitaxel (PTX), a water
      insoluble drug. The drug-loaded cationic micelles can then interact with siRNA to
      form stable complexes (PTX/DA3/siRNA). The PTX/DA3/siRNA showed significantly
      enhanced inhibition of cancer cell growth. When administered into tumor-bearing
      animals, the PTX/DA3/siRNA demonstrated significant suppression of tumor growth,
      providing potential usefulness in clinical settings.

PMID- 22613209
TI  - Identification of an intracellular M17 family leucine aminopeptidase that is
      required for virulence in Staphylococcus aureus.
AB  - Staphylococcus aureus is a highly virulent bacterial pathogen capable of causing
      a variety of ailments throughout the human body. It is a major public health
      concern due to the continued emergence of highly pathogenic methicillin resistant
      strains (MRSA) both within hospitals and in the community. Virulence in S. aureus
      is mediated by an array of secreted and cell wall associated virulence factors,
      including toxins, hemolysins and proteases. In this work we identify a leucine
      aminopeptidase (LAP, pepZ) that strongly impacts the pathogenic abilities of S.
      aureus. Disruption of the pepZ gene in either Newman or USA300 resulted in a
      dramatic attenuation of virulence in both localized and systemic models of
      infection. LAP is required for survival inside human macrophages and gene
      expression analysis shows that pepZ expression is highest in the intracellular
      environment. We examine the cellular location of LAP and demonstrate that it is
      localized to the bacterial cytosol. These results identify for the first time an
      intracellular leucine aminopeptidase that influences disease causation in a Gram
      positive bacterium.

PMID- 22613210
TI  - The role of cGMP signalling in regulating life cycle progression of Plasmodium.
AB  - The 3'-5'-cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is
      the main mediator of cGMP signalling in the malaria parasite. This article
      reviews the role of PKG in Plasmodium falciparum during gametogenesis and blood
      stage schizont rupture, as well as the role of the Plasmodium berghei orthologue
      in ookinete differentiation and motility, and liver stage schizont development.
      The current views on potential effector proteins downstream of PKG and the
      mechanisms that may regulate cyclic nucleotide levels are presented.

PMID- 22613211
TI  - Efficacy of pentane, toluene, and benzene to support aerobic cometabolism of
      ethylene dibromide.
AB  - The ability of pentane, benzene, and toluene to support aerobic cometabolism of
      ethylene dibromide (1,2-dibromoethane, EDB) was evaluated. A pentane enrichment
      culture cometabolized EDB, with a transformation capacity of 0.35 MUmol EDB/mg
      biomass (66.2 MUg EDB/mg biomass) in the absence of growth substrate. It also
      cometabolized EDB while actively growing on pentane. However, enrichment cultures
      grown on benzene or toluene could not cometabolize EDB, with or without their
      respective growth substrates.

PMID- 22613212
TI  - Investigation of the component of Lycopodium serratum extract that inhibits
      proliferation and mediates apoptosis of human HL-60 leukemia cells.
AB  - In this study, we investigate a plant commonly used in herbal medicines,
      Lycopodium serratum, which is believed to have anti-cancer properties. An
      alcoholic extract of L. serratum (LSE) was investigated for its ability to induce
      apoptosis in cultured human promyelocytic leukemia HL-60 cells. Treatment of HL
      60 cells with various concentrations of LSE (6-100 MUg/mL) resulted in a sequence
      of events characteristic of apoptosis, including loss of cell viability,
      morphological changes, and increased sub-G(1) DNA content. Serratenediol (SE), a
      known biologically active agent, was isolated from MC fraction of LSE and was
      able to demonstrate significant and dose-dependent growth inhibitory effects on
      HL-60 cells. Similar to the effects observed with the crude LSE, the SE-related
      effects included the formation of apoptotic bodies and fragmented DNA, as well as
      the accumulation of DNA in the sub-G(1) phase of the cell cycle. Analysis of the
      mechanism of these events indicated that SE treated cells had an increased ratio
      of Bax/Bcl-xL, released the cytochrome c, activated caspase-9, -3, and cleaved
      poly-ADP-ribose polymerase (PARP); these observations are hallmarks of apoptotic
      events. Thus, the results suggest that SE can induce apoptosis via regulating the
      ratio of Bax/Bcl-xL in HL-60 cell lines.

PMID- 22613213
TI  - The pyranoxanthone inophyllin A induces oxidative stress mediated-apoptosis in
      Jurkat T lymphoblastic leukemia cells.
AB  - Inophyllin A (INO-A), a pyranoxanthone isolated from the roots of Calophyllum
      inophyllum represents a new xanthone with potential chemotherapeutic activity. In
      this study, the molecular mechanism of INO-A-induced cell death was investigated
      in Jurkat T lymphoblastic leukemia cells. Assessment of phosphatidylserine
      exposure confirmed apoptosis as the primary mode of cell death in INO-A-treated
      Jurkat cells. INO-A treatment for only 30 min resulted in a significant increase
      of tail moment which suggests that DNA damage is an early apoptotic signal.
      Further flow cytometric assessment of the superoxide anion level confirmed that
      INO-A induced DNA damage was mediated with a concomitant generation of reactive
      oxygen species (ROS). Investigation on the thiols revealed an early decrease of
      free thiols in 30 min after 50 MUM INO-A treatment. Using tetramethylrhodamine
      ethyl ester, a potentiometric dye, the loss of mitochondrial membrane potential
      (MPP) was observed in INO-A-treated cells as early as 30 min. The INO-A-induced
      apoptosis progressed with the simultaneous activation of caspases-2 and -9 which
      then led to the processing of caspase-3. Taken together, these data demonstrate
      that INO-A induced early oxidative stress, DNA damage and loss of MMP which
      subsequently led to the activation of an intrinsic pathway of apoptosis in Jurkat
      cells.

PMID- 22613214
TI  - Evaluation of antiarthritic activity of isoeugenol in adjuvant induced arthritis
      in murine model.
AB  - Isoeugenol, a component of clover oil, possesses potent anti-inflammatory and
      antioxidant activity. In the present study, we investigated the effect on
      experimentally induced adjuvant arthritis in rats. Induction of arthritis in
      adjuvant exposed rats was confirmed by appearance of several physical symptoms
      such as redness, swelling and stiffness of paws, radiographic analysis revealing
      joint damage, soft tissue swelling of the footpad, histopathologic changes and
      expression of proinflammatory enzymes and mediators in the joint tissue.
      Treatment of rats with isoeugenol, however, conferred a significant protection
      against almost all the investigated parameters. Isoeugenol significantly and dose
      dependently attenuated arthritic index, paw circumference, joint stiffness and
      the levels of proinflammatory mediators. Exposure to isoeugenol inhibited the
      release of nitric oxide and proinflammatory cytokines the including PGE(2) and
      TNFalpha from lipopolysaccharide primed macrophages. Isoeugenol also showed a
      significant analgesic activity in acetic acid-induced writhing model. Further,
      unlike most antiarthritic drugs, isoeugenol had no damaging effect on gastric
      mucosa, which makes it a favorable antiarthritic drug. Thus, the results obtained
      in the present study indicate isoeugenol to possess a promising antiarthritic
      activity and further advocate the efficacy of natural products as antiarthritic
      therapeutics.

PMID- 22613215
TI  - Estrogenic/antiestrogenic activities of a Epimedium koreanum extract and its
      major components: in vitro and in vivo studies.
AB  - The estrogenic and antiestrogenic activities of Epimedii Herba, which is a
      traditional medicinal herb used in Korea and China were investigated in this
      study. The in vitro estrogen receptor (ER) mediated estrogenic/antiestrogenic
      activities of an Epimedii Herba extract (Epi ext) and its major components were
      determined using an estrogen responsive element driven reporter gene assay in MCF
      7/ERE and HEK293T cells. The Epi ext exhibited ERalpha- and ERbeta-mediated
      estrogenic activity with an EC(50) of 5.0 and 17.8 MUM in HEK293T cells,
      respectively. Prenylflavonoid glycosides such as icariin (ICA), epimedin A, B,
      and C did not show any in vitro estrogenic or antiestrogenic activities. Icaritin
      (ICT) and quercetin exhibited in vitro ER mediated estrogenic activity with a
      more potent interaction with ERbeta. In vivo estrogenic activities of the Epi
      ext, ICA and ICT were compared using an uterotrophic assay. Although the potency
      of in vitro estrogenic activity was in the order of ICT>Epi ext>ICA, ICA had the
      strongest estrogenic activity and next ICT in ovariectomized rats. These results
      collectively suggest that phytoestrogens possess both estrogenic and
      antiestrogenic activity, and that the differential expression of these two
      compounds with opposing activities is dependent on the physiological environment
      in terms of estrogen level, which may be the case in humans.

PMID- 22613216
TI  - Adenosinergic modulation of the imidazoline I1-receptor-dependent hypotensive
      effect of ethanol in acute renal failure.
AB  - We reported that inhibition of central sympathetic pools of imidazoline I(1)
      receptors abolishes the hypotensive effect of ethanol in rats with glycerol
      induced acute renal failure (ARF). This study investigated whether adenosine
      receptors modulate the ethanol-I(1)-receptor interaction. The effect of selective
      blockade of adenosine A(1), A(2A), or A(2B) receptors on hemodynamic responses to
      ethanol in the absence and presence of the I(1)-receptor agonist moxonidine was
      determined in ARF rats. Ethanol (1g/kg i.v.) decreased and increased blood
      pressure (BP) and heart rate (HR), respectively. Pretreatment with moxonidine
      abolished the hypotensive but not the tachycardic effect of ethanol. The
      hypotensive effect of ethanol remained unaltered after selective blockade of
      A(1), A(2A), or A(2B) receptors with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX)
      and 8-(3-chlorostyryl) caffeine (CSC) and alloxazine, respectively. Neither was
      ethanol hypotension affected after inhibition of adenosine uptake by dipyridamole
      (DPY). Alternatively, the ability of moxonidine to abolish ethanol hypotension
      was still evident in presence of alloxazine whereas it disappeared or weakened in
      rats pretreated with CSC and DPCPX, respectively. These findings implicate
      adenosine A(2A) receptors in the moxonidine-evoked inhibition of the hypotensive
      action of ethanol. A modulatory role for adenosine A(1) site in the ethanol-I(1)
      receptor interaction is also possible through as yet unidentified mechanism.

PMID- 22613217
TI  - Antitumor and immunostimulatory activity of a polysaccharide-protein complex from
      Scolopendra subspinipes mutilans L. Koch in tumor-bearing mice.
AB  - Scolopendra subspinipes mutilans L. Koch has been used for cancer treatment in
      traditional Chinese medicine for hundreds of years. In this study, the effects of
      a polysaccharide-protein complex from Scolopendra subspinipes mutilans L. Koch
      (SPPC) on the tumor growth and immune function were assessed in sarcoma S180 and
      hepatoma H22 bearing mice. Results showed that SPPC significantly inhibited the
      growth of S180 transplanted in mice and prolonged the survival time of H22-
      bearing mice. In S180-bearing mice, it promoted specific and nonspecific immune
      response as evidenced by enhancing the activities of natural killer (NK) cells,
      cytotoxic T lymphocytes (CTL) and the ratio of Th1/Th2 cytokines, and increasing
      the percentages of CD4(+) T cells, B cells and NK cells. Furthermore, SPPC not
      only significantly inhibited mRNA expression and production of the
      immunosuppressive cytokines (IL-10 and TGF-beta), but also diminished arachidonic
      acid (AA)-metabolizing enzymes (COX-2 and CYP4A) and their products (PGE(2) and
      20-HETE) in tumor-associated macrophages (TAMs). Taken together, our results
      indicate that SPPC inhibits tumor growth in vivo by improving antitumor immune
      responses at least partly via downregulating AA-metabolic pathways in TAMs, and
      could act as an anti-tumor agent with immunomodulatory activity.

PMID- 22613218
TI  - Myocardial biopsies differentiate between myocyte- and endothelial-targeted
      myocarditis.

PMID- 22613220
TI  - Worms and diarrhoea in sheep: a complex interaction.

PMID- 22613219
TI  - Acoustic characteristic of catathrenia and snoring: different subtypes of
      catathrenia.
AB  - OBJECTIVE: Catathrenia (nocturnal groaning) is a rare condition characterized by
      monotonous irregular sounds that occur during sleep. Not infrequently,
      catathrenia has been confused with expiratory snoring. We aimed to clarify the
      subtypes of catathrenia and differentiate them from snoring using sound analyses.
      METHODS: We enrolled five patients with catathrenia who were confirmed by
      overnight polysomnography (PSG). They underwent clinical and physical evaluation,
      including craniofacial and oromandibular examination, and fulfilled sleep-related
      questionnaires. Catathrenia and snoring of patients were analyzed acoustically
      with a Multi-Dimensional Voice Program. RESULTS: All subjects were young (mean
      31.0 years, 22-39) and slim (mean 20.5 kg/m(2) body mass index) women. PSG
      findings showed normal ranged apnea-hypopnea indices (mean 0.8+/-1.4/h),
      respiratory disturbance indices (2.6+/-1.7/h), and well-preserved sleep
      architecture. The number of catathrenia during PSG varied between one and 55 per
      patient, with sound duration ranging from 0.3 to 15.1 s. Of a total of 113
      episodes, 70 (61.9%) occurred during REM sleep and 43 (38.1%) during NREM sleep.
      All patients showed light snoring through the PSG night. In the sound analysis
      three patients demonstrated monotonous sinusoidal catathrenia sounds, which were
      of normal ranged fundamental frequency. The other two had sawtooth-shaped
      catathrenia signals with higher fundamental frequency. In contrast, snoring had
      an irregular signal in all patients. CONCLUSIONS: We observed that catathrenia
      had morphologic regularity, with two types of sound pitches, and snoring had a
      different signal from catathrenia by sound analysis.

PMID- 22613222
TI  - Space plant biology research in Lithuania.
AB  - In 1957, the Soviet Union launched the first artificial Earth satellite,
      initiating its space exploration programs. Throughout the rest of the twentieth
      century, the development of these space programs received special attention from
      Soviet Union authorities. Scientists from the former Soviet Republics, including
      Lithuania, participated in these programs. From 1971 to 1990, Lithuanians
      designed more than 20 experiments on higher plant species during space flight.
      Some of these experiments had never before been attempted and, therefore, made
      scientific history. However, the formation and development of space plant biology
      research in Lithuania or its origins, context of formation, and placement in a
      worldwide context have not been explored from a historical standpoint. By
      investigating these topics, this paper seeks to construct an image of the
      development of a very specific field of science in a small former Soviet
      republic.

PMID- 22613221
TI  - Elevated fat skatole levels in immunocastrated, surgically castrated and entire
      male pigs with acute dysentery.
AB  - Boar taint is due to androstenone and skatole (3-methyl-indole) accumulation in
      fat tissues. During a study to investigate the effect of immunocastration on
      fattening pigs, an outbreak of acute dysentery occurred caused by Lawsonia
      intracellularis and Brachyspira hyodysenteriae and resulted in cachexia and high
      mortality. Low androstenone levels in the immunocastrates (0.25 +/- 0.04 MUg/g
      liquid fat) suggested that the immunocastration had been effective, but unusually
      high skatole concentrations in fat tissues were found not only in entire males,
      but also in surgical castrates and immunocastrates (0.22 +/- 0.15, 0.14 +/- 0.08
      and 0.18 +/- 0.14 MUg/g liquid fat, respectively). The findings suggest that boar
      taint can arise in cases of intestinal infections, even in castrated pigs.

PMID- 22613223
TI  - Misperception of patients with type 2 diabetes about diet and physical activity,
      and its effects on readiness to change.
AB  - BACKGROUND: The aim of the present study was to assess misperceptions about
      lifestyle among patients with type 2 diabetes and their effects on readiness to
      change. METHODS: Nine hundred and forty patients, with an HbA1c >7% and a body
      mass index >25 kg/m(2), from 57 general practices participated in a cross
      sectional survey. Misperceptions of lifestyle (fruit, vegetable, and fat
      consumption, as well as physical activity) and readiness to change were
      determined with validated questionnaires. Logistic regression analysis calculated
      the association of misperception with readiness to change. RESULTS: The response
      rate was 55.4%. Misperception existed for all lifestyle behaviors (physical
      activity, 41.5%; consumption of fruit, 40.1%; consumption of vegetables, 69.2%;
      consumption of fat, 21.6%). Misperception significantly affected readiness to
      change the relevant lifestyle (odds ratios [95% confidence intervals] ranging
      from 2.67 [1.68-4.23] to 1.80 [1.16-2.79]), except in the case of fruit
      consumption. The degree of misperception varied greatly between the different
      lifestyle behaviors and was somewhat larger (1-10%) than that in the general
      Dutch population. CONCLUSIONS: Patients with type 2 diabetes misperceive their
      lifestyle behaviors, which hinders lifestyle changes. The variations in
      misperception and readiness to change show that diversity should be considered in
      lifestyle counseling for patients with type 2 diabetes.

PMID- 22613224
TI  - Curcumin induces permanent growth arrest of human colon cancer cells: link
      between senescence and autophagy.
AB  - Curcumin, a natural polyphenol derived from the rhizome of Curcuma longa, is a
      potent anticancer agent, which restricts tumor cell growth both in vitro and in
      vivo. Thus far curcumin was shown to induce death of cancer cells. This study
      reports the induction of cellular senescence of human colon cancer cells HCT116
      upon curcumin treatment. The SA-beta-galactosidase activation was observed both
      in p53+/+ and p53-/- cells, however the latter ones were less sensitive to the
      prosenescent activity of curcumin. Upregulation of p53 and p21 proteins was
      observed in p53+/+ HCT116, while p53-independent induction of p21 was noticed in
      p53-/- HCT116. Moreover, the senescence of HCT116 cells was accompanied by
      autophagy, that was confirmed by electron microscopy observations of
      autophagosomes in the curcumin-treated cells as well as LC3-II expression,
      punctue staining of LC3 and increased content of acidic vacuoles. Inhibition of
      autophagy, due to the diminished expression of ATG5 by RNAi decreased the number
      of senescent cells induced by curcumin, but did not lead to increased cell death.
      Altogether, we demonstrated a new antitumor activity of curcumin leading to
      cancer cell senescence and revealed the presence of a functional link between
      senescence and autophagy in curcumin-treated cells.

PMID- 22613226
TI  - Graphene oxide based fluorescent aptasensor for adenosine deaminase detection
      using adenosine as the substrate.
AB  - We present a novel fluorescent aptasensor for simple and accurate detection of
      adenosine deaminase (ADA) activity and inhibition on the basis of graphene oxide
      (GO) using adenosine (AD) as the substrate. This aptasensor consists of a dye
      labeled single-stranded AD specific aptamer, GO and AD. The fluorescence
      intensity of the dye-labeled AD specific aptamer is quenched very efficiently by
      GO as a result of strong pi-pi stacking interaction and excellent electronic
      transference of GO. In the presence of AD, the fluorescence of the GO-based probe
      is recovered since the competitive binding of AD and GO with the dye-labeled
      aptamer prevents the adsorption of dye-labeled aptamer on GO. When ADA was
      introduced to this GO-based probe solution, the fluorescence of the probe was
      quenched owing to ADA can convert AD into inosine which has no affinity to the
      dye-labeled aptamer, thus allowing quantitative investigation of ADA activity.
      The as-proposed sensor is highly selective and sensitive for the assay of ADA
      activity with a detection limit of 0.0129U/mL in clean buffer, which is more than
      one order of magnitude lower than the previous reports. Meanwhile, a good linear
      relationship with the correlation coefficient of R=0.9922 was obtained by testing
      5% human serum containing a series of concentrations of ADA. Additionally, the
      inhibition effect of erythro-9-(2-hydroxy-3-nonyl) adenine on ADA activity was
      investigated in this design. The GO-based fluorescence aptasensor not only
      provides a simple, cost-effective and sensitive platform for the detection of ADA
      and its inhibitor but also shows great potential in the diagnosis of ADA-relevant
      diseases and drug development.

PMID- 22613227
TI  - Analysis of risk factors for extubation failure in subjects submitted to non
      emergency elective intracranial surgery.
AB  - BACKGROUND: Extubation failure is defined as the re-institution of respiratory
      support ranging from 24 to 72 hours following scheduled extubation and occurs in
      2% to 25% of extubated patients. The aim of this study was to determine clinical
      and surgical risk factors that may predict extubation failure in patients
      submitted to non-emergency intracranial surgery. METHODS: This was a prospective
      observational cohort study. The study was carried out on 317 subjects submitted
      to non-emergency intracranial surgery for tumors, aneurysms, and arteriovenous
      malformation. Preoperative assessment was performed and subjects were followed up
      for the determination of extubation failure until either discharge from hospital
      or death. RESULTS: Twenty-six (8.2%) of the 317 subjects experienced extubation
      failure following surgery. The following variables were considered for the
      multivariate analysis: level of consciousness at the time of extubation, duration
      of mechanical ventilation prior to extubation, sex and the use of intraoperative
      mannitol. The multivariate analysis determined that the most important variable
      for extubation failure was the level of consciousness at the time of extubation
      (P = .001), followed by female sex, which also showed to be significant (P =
      .006). CONCLUSIONS: Lower level of consciousness (GCS 8T-10T) and female sex were
      considered risk factors for extubation failure in subjects submitted to elective
      intracranial surgery.

PMID- 22613225
TI  - Genome-wide expression and methylation profiling in the aged rodent brain due to
      early-life Pb exposure and its relevance to aging.
AB  - In this study, we assessed global gene expression patterns in adolescent mice
      exposed to lead (Pb) as infants and their aged siblings to identify reprogrammed
      genes. Global expression on postnatal day 20 and 700 was analyzed and genes that
      were down- and up-regulated (>=2 fold) were identified, clustered and analyzed
      for their relationship to DNA methylation. About 150 genes were differentially
      expressed in old age. In normal aging, we observed an up-regulation of genes
      related to the immune response, metal-binding, metabolism and
      transcription/transduction coupling. Prior exposure to Pb revealed a repression
      in these genes suggesting that disturbances in developmental stages of the brain
      compromise the ability to defend against age-related stressors, thus promoting
      the neurodegenerative process. Overexpression and repression of genes
      corresponded with their DNA methylation profile.

PMID- 22613228
TI  - VGF peptides upon osmotic stimuli: changes in neuroendocrine regulatory peptides
      1 and 2 in the hypothalamic-pituitary-axis and plasma.
AB  - VGF or VGF nerve growth factor inducible is a protein that has been found to play
      a role in regulating energy homeostasis and metabolism. From VGF precursor derive
      two neuroendocrine regulatory peptides NERP-1 and NERP-2 that,
      intracerebroventricular (icv) injected, modulate the antidiuretic hormone (ADH)
      release. Thus, we investigated possible modulations of the NERPs and other VGF
      peptides (namely VGF C-terminus, TLQP and PGH) in the hypothalamic-pituitary
      axis, adrenal gland and plasma upon osmotic stimuli. The latter tissues were
      studied using water deprived (WD), salt loaded (SL), rehydrated after salt cargo
      and control rats by immunohistochemistry and immunoenzymatic assays. The high
      performance liquid chromatography ensured the endogenous presence of the two
      NERPs in both plasma and hypothalamus. Upon dehydration, NERP-1 levels increased
      in the median eminence (M.E.) only, while using SL rats, the values of both NERPs
      increased in the M.E. and even in the hypothalamus. Conversely, in the blood of
      WD and SL rats, the levels of NERP-1 and NERP-2 decreased while, using pituitary
      from both rat groups, levels of NERP-2 increased and those of NERP-1 decreased.
      Reduction in the VGF C-terminus peptide levels was observed exclusively in the
      M.E. (using WD rats) and pituitary (using WD and SL rats), while PGH and TLQP
      peptide levels never changed in all tissues tested. By immunohistochemistry, the
      VGF peptides studied (apart from the TLQP peptides) were present in the
      hypothalamic and pituitary ADH containing neurons of the control rats, while
      using WD and SL rats, an immunostaining increase was selectively revealed for VGF
      C-terminus peptides in the hypothalamic neurons that produce ADH. All VGF changes
      found using SL rats disappeared after only 1h of rehydration. In conclusion, we
      hypothesize that NERPs may be involved in both autocrine and endocrine mechanisms
      important for the fluid balance.

PMID- 22613229
TI  - Involvement of CX3CR1 in bone cancer pain through the activation of microglia p38
      MAPK pathway in the spinal cord.
AB  - Previous studies have demonstrated that fractalkine, a newly discovered
      chemokine, is implicated in spinal cord neuron-to-microglia activation signaling
      as well as mediation of neuropathic and inflammatory pain via its sole receptor
      CX3CR1, which is specifically expressed on microglia. However, whether it is
      involved in bone cancer pain (BCP) and the underlying mechanisms have not been
      elucidated. In this study we utilized a Sprague-Dawley rat animal model, and our
      findings indicated that on day 6, 12, and 18 following bone cancer pain induced
      by Walker 256 cell inoculation, the expression level of CX3CR1 in the spinal cord
      gradually increased. Intrathecal injection of a neutralizing antibody against
      CX3CR1 not only delayed the initiation of mechanical allodynia, but also
      attenuated established pain sensitization of BCP rats. Furthermore, we
      demonstrated that blockade of CX3CR1 suppressed the activation of microglia and
      the expression of p38 mitogen-activated protein kinase (MAPK) in the spinal cord
      in BCP rats. These results suggest a new mechanism of BCP, in which the microglia
      CX3CR1/p38 signaling cascade potentially plays an important role in facilitating
      pain processing in BCP rats.

PMID- 22613231
TI  - Expression of the Parkinson's disease protein DJ-1 during the differentiation of
      neural stem cells.
AB  - DJ-1 is a key neuroprotective factor and its loss-of-function mutations cause an
      autosomal recessive, early-onset form of familial Parkinson's disease at the
      chromosomal PARK7 locus. However, the expression of DJ-1 during the
      differentiation of neural stem cells has not been fully elucidated. In this
      study, we investigated the expression of DJ-1 quantitatively using fluorescence
      immunocytochemistry and flow cytometry for differentiated neural stem cells from
      the cortex of the 14-day mouse embryos. We found that DJ-1 was co-expressed with
      the neuron-specific enolase and glial fibrillary acidic proteins, and also its
      expression was significantly increased in neurons and astrocytes with a prolonged
      differentiation period. These findings strongly suggest that DJ-1 is closely
      associated with the differentiation of neural stem cells.

PMID- 22613233
TI  - Bioactivity guided isolation of analgesic and anti-inflammatory constituents of
      Cnestis ferruginea Vahl ex DC (Connaraceae) root.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cnestis ferruginea (CF) Vahl ex DC (Connaraceae)
      is a shrub widely used in Traditional African Medicine (TAM) for the treatment of
      various painful and inflammatory conditions. AIM OF THE STUDY: To isolate the
      active pharmacological constituents responsible for the anti-inflammatory and
      antinociceptive properties of the methanolic root extract of C. ferruginea.
      MATERIALS AND METHODS: The crude methanolic root extract of CF was sequentially
      fractionated into four sub extracts (chloroform, ethylacetate, n-butanol and the
      remaining aqueous fraction). The aqueous-butanol fractions, having showed
      significant inhibition of inflammation and pain, were subjected to fractionation
      through successive column chromatography on silica gel 60-120 mesh, eluted with a
      gradient of CHCl(3)-MeOH. Sixty five fractions were collected; fractions with
      similar TLC profiles were grouped into seven major fractions (1-7). Fraction 4
      being the most active in bioassay was rechromatographed to obtain CF-2. Analgesic
      activity was evaluated using the acetic acid-induced writhing and hot plate tests
      in mice while carrageenan induced paw oedema test was used to investigate the
      anti-inflammatory actions of the fractions obtained. RESULT: Amentoflavone (CF-2)
      was isolated from the aqueous/n-butanol fraction. CF-2 (12.5, 25 and 100 mg/kg;
      p.o) produced significant (P<0.05) dose dependent inhibition of pain response
      elicited by acetic acid and increased nociceptive reaction latency in hot plate
      test. In addition it produced significant (P<0.05) dose-dependent inhibition of
      oedema in the carrageenan-induced inflammation. CONCLUSION: This study showed
      that amentoflavone is responsible for the analgesic and anti-inflammatory
      activity of Cnestis ferruginea.

PMID- 22613232
TI  - Cardiopulmonary bypass and serum thyroid hormone profile in pediatric patients
      with congenital heart disease.
AB  - OBJECTIVE: To study the effect of cardiopulmonary bypass (CPB) on serum thyroid
      hormone profile in children undergoing open-heart surgery. DESIGN: Prospective
      cross-sectional study. SETTING: Multispecialty tertiary level referral center.
      PATIENTS: One hundred consecutive patients (age 15.9 +/- 14.6 months, weight 6.7
      +/- 2.5 kg) undergoing open-heart surgery under CPB. INTERVENTIONS: None. OUTCOME
      MEASURES: Levels and trends of serum total thyroxine (TT4), free thyroxine (FT4),
      total tri-iodothyronine (TT3), free tri-iodothyronine (FT3) and thyroid
      stimulating hormone (TSH), survival, inotropic score, duration of mechanical
      ventilation, postoperative complications. RESULTS: TT4 levels were 9.08 +/- 3.6,
      6.4 +/- 2.5, 6.24 +/- 2.1, 6.43 +/- 2.4, 7.20 +/- 3.0 ug/dL at baseline and at 1,
      24, 48 and 72 hours; FT4 levels were 1.82 +/- 0.5, 1.49 +/- 0.3, 1.29 +/- 0.3,
      1.32 +/- 0.4, and 1.43 +/- 0.5 ng/dL; TT3 levels were 1.81 +/- 0.4, 1.31 +/- 0.3,
      0.99 +/- 0.2, 1.0 +/- 0.37, and 1.17 +/- 0.48 ng/ml; FT3 levels were 4.09 +/-
      1.0, 3.02 +/- 0.8, 2.21 +/- 0.6, 2.22 +/- 0.7, and 2.66 +/- 1.05 pg/ml; TSH
      levels were 5.40 +/- 3.8, 2.0 +/- 3.1, 1.24 +/- 1.1, 2.90 +/- 3.3, and 4.03 +/-
      3.4 mIU/L. There was significant fall (29.1% for FT4, 32.1% for TT4, 77% for TSH,
      46% for FT3 and 45% for TT3, p < 0.0001). When area under curve (AUC) TT4 was
      compared between survivors (n = 87) and nonsurvivors (n = 12), significantly
      larger AUC was seen in survivors (492.81 +/- 158.6) than nonsurvivors (360.75 +/-
      179.6 p = 0.0125). In survivors >72 hours, AUC TT4 was larger in patients with
      uneventful postoperative course versus those with postoperative complications
      (516.48 +/- 18.6 vs. 394.78 +/- 29.9, p = 0.001). AUC TT4 showed significant
      inverse correlation with inotropic score and borderline inverse correlation with
      duration of mechanical ventilation. CONCLUSION: Children undergoing surgery under
      CPB showed significant fall in thyroid hormones. Because TT4 level is modifiable,
      prophylactic administration of TT4 for improving outcomes needs to be studied
      further.

PMID- 22613235
TI  - The 'survival perceptions': time to put some Bacon on our plates?

PMID- 22613230
TI  - Fluid reasoning deficits in children with ADHD: evidence from fMRI.
AB  - Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with deficits in
      fluid reasoning, which may be related to self-regulation of cognition and
      behavior, and requires intact attention, working memory, and inhibition skills.
      No functional magnetic resonance imaging (fMRI) studies have directly examined
      fluid reasoning in ADHD which is surprising given that studies demonstrate a
      consistent network of brain regions involved in fluid reasoning that are also
      implicated in the pathogenesis of ADHD. Twenty-two right-handed, non-medicated
      children (12 ADHD, 10 controls) ages 8-12 years completed a fluid reasoning task
      during which fMRI data were collected. The primary comparison of interest was
      activation during the fluid reasoning compared to the control condition.
      Behavioral data showed that children with ADHD tended to be less accurate with
      faster reaction times in the fluid reasoning condition compared to controls, and
      were significantly less accurate in the control condition. Controls activated
      more than participants with ADHD in the right intraparietal sulcus and the left
      lateral cerebellum in the fluid reasoning condition. Results showed
      hypoactivation in ADHD in regions critical for fluid reasoning. These results add
      to the literature suggesting a role for parietal and cerebellar regions in
      cognition and ADHD.

PMID- 22613234
TI  - Antitumor activity of the methanolic extract of Ammannia baccifera L. against
      Dalton's ascites lymphoma induced ascitic and solid tumors in mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: India is a rich source of medicinal plants and a
      number of plant extracts are used against diseases in various systems of medicine
      such as Ayurveda, Unani and Siddha. Only a few of them have been scientifically
      explored. One of such plants is Ammannia baccifera L., traditionally used as an
      antitumor agent. AIM OF THE STUDY: The objective of the present study was to
      explore the anticancer activity of the methanol extract of A. baccifera against
      Dalton's ascites lymphoma (DAL)-bearing Swiss albino mice and in vitro
      cytotoxicity against human cervical cancer cell line (HeLa). MATERIALS AND
      METHODS: In vitro cytotoxic effects of A. baccifera was evaluated against HeLa
      and NIH 3T3 cells using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide] method. Anticancer activity of the extract was evaluated in Swiss albino
      mice against DAL cell line at the doses of 100 and 200mg/kg p.o. The extract was
      administered to animals for 14 consecutive days. After 12h fasting from last
      dose, the mice were sacrificed and the anticancer effect of A. baccifera was
      assessed by evaluating tumor volume, viable and nonviable tumor cell count, tumor
      weight, hematological parameters and certain antioxidant biochemical parameters
      against DAL bearing control group. RESULTS: The extract of A. baccifera was
      cytotoxic to the HeLa cancer cell line but relatively non-toxic to the normal
      cell line NIH 3T3. A. baccifera extract treatment resulted in significant
      decreases in tumor volume, viable cell count and tumor weight and enhanced the
      life span of DAL bearing mice. Hematological parameters such as RBC, hemoglobin
      and lymphocyte count reverted to normal level in A. baccifera treated mice. The
      extract also significantly (p<0.05) decreased the levels of lipid peroxidation
      and increased the activities of GSH, GPx, SOD and CAT. The anticancer effects of
      the A. baccifera extract is comparable with that of the standard drug 5
      Fluorouracil. CONCLUSION: The results showed that the methanol extract of A.
      baccifera is effective in inhibiting the tumor growth in ascetic models that is
      comparable to 5-fluorouracil. This plant has potential in the development of
      anticancer therapy and this study scientifically validated the folklore use of
      this plant.

PMID- 22613236
TI  - Standardisation of terms in the physiotherapy profession.

PMID- 22613237
TI  - Patient-centred communication is associated with positive therapeutic alliance: a
      systematic review.
AB  - QUESTION: During the patient-therapist encounter, which communication factors
      correlate with constructs of therapeutic alliance? DESIGN: Systematic review.
      PARTICIPANTS: Clinicians and patients in primary, secondary or tertiary care
      settings. MEASURES: Studies had to investigate the association between
      communication factors (interaction styles, verbal factors or non-verbal factors)
      and constructs of the therapeutic alliance (collaboration, affective bond,
      agreement, trust, or empathy), measured during encounters between health
      practitioners and patients. RESULTS: Among the twelve studies that met the
      inclusion criteria, 67 communication factors were identified (36 interaction
      styles, 17 verbal factors and 14 non-verbal factors). The constructs of
      therapeutic alliance in the included studies were rapport, trust, communicative
      success and agreement. Interaction styles that showed positive large correlations
      with therapeutic alliance were those factors that help clinicians to engage more
      with patients by listening to what they have to say, asking questions and showing
      sensitivity to their emotional concerns. Studies of verbal and non-verbal factors
      were scarce and inconclusive. CONCLUSIONS: The limited evidence suggests patient
      centred interaction styles related to the provision of emotional support and
      allowing patient involvement in the consultation process enhance the therapeutic
      alliance. Clinicians can use this evidence to adjust their interactions with
      patients to include communication strategies that strengthen the therapeutic
      alliance.

PMID- 22613238
TI  - Kinesio Taping reduces disability and pain slightly in chronic non-specific low
      back pain: a randomised trial.
AB  - QUESTION: Does Kinesio Taping reduce disability, pain, and kinesiophobia in
      people with chronic non-specific low back pain? DESIGN: Randomised trial, with
      concealed allocation, assessor blinding, and intention-to-treat analysis.
      PARTICIPANTS: Sixty adults with chronic non-specific low back pain. INTERVENTION:
      The experimental intervention was Kinesio Taping over the lumbar spine for one
      week; the control intervention was sham taping. OUTCOME MEASURES: The following
      outcomes were measured at baseline, immediately after the week with the tape in
      situ, and four weeks later: Oswestry Disability Index, Roland- Morris Low Back
      Pain and Disability Questionnaire, pain on a 10-cm visual analogue scale, Tampa
      kinesiophobia scale, trunk flexion range of motion, and the McQuade test of trunk
      muscle endurance. RESULTS: At one week, the experimental group had significantly
      greater improvement in disability, by 4 points (95% CI 2 to 6) on the Oswestry
      score and by 1.2 points (95% CI 0.4 to 2.0) on the Roland-Morris score. However,
      these effects were not significant four weeks later. The experimental group also
      had a greater decrease in pain than the control group immediately after treatment
      (mean between-group difference 1.1cm, 95% CI 0.3 to 1.9), which was maintained
      four weeks later (1.0cm, 95% CI 0.2 to 1.7). Similarly trunk muscle endurance was
      significantly better at one week (by 23 sec, 95% CI 14 to 32) and four weeks
      later (by 18 sec, 95% CI 9 to 26). Other outcomes were not significantly
      affected. CONCLUSION: Kinesio Taping reduced disability and pain in people with
      chronic non-specific low back pain, but these effects may be too small to be
      clinically worthwhile. TRIAL REGISTRATION: ACTRN12612000402842.

PMID- 22613239
TI  - Balance training reduces fear of falling and improves dynamic balance and
      isometric strength in institutionalised older people: a randomised trial.
AB  - QUESTION: What is the effect of a balance training protocol with the Biodex
      Balance System in institutionalised older people with fear of falling? DESIGN:
      Randomised controlled trial with concealed allocation and assessor blinding.
      PARTICIPANTS: Forty older people who lived in a nursing home and had fear of
      falling. INTERVENTION: The experimental group completed a 12-week balance
      training protocol based on balancing/rebalancing training with the Biodex Balance
      System, with two sessions per week. During the training period, participants in
      both groups received the same multidisciplinary care (such as physiotherapy,
      occupational therapy and nursing) that they usually received in the nursing home.
      OUTCOME MEASURES: The primary outcome was fear of falling (Falls Efficacy Scale
      International questionnaire). Secondary outcomes were dynamic balance (Fall Risk
      Test) and isometric strength (torque of knee flexor and extensor isometric
      strength measured with an isokinetic dynamometer). Outcome measures were taken
      before and after the training program protocol. RESULTS: Compared to the control
      group, the exercise group had significantly greater improvements at 12 weeks in
      fear of falling (by 8 points, 95% CI 4 to 12), in dynamic balance (by 2 degrees,
      95% CI 1 to 3), and in isometric strength of the knee flexors (by 7Nm, 95% CI 3
      to 11) and knee extensors (by 7Nm, 95% CI 1 to 13). CONCLUSION: The training
      program was feasible and effective in reducing fear of falling and improving
      dynamic balance and isometric strength in institutionalised older people with
      fear of falling. TRIAL REGISTRATION: ISRCTN21695765.

PMID- 22613240
TI  - Circuit class therapy can provide a fitness training stimulus for adults with
      severe traumatic brain injury: a randomised trial within an observational study.
AB  - QUESTIONS: Can circuit class therapy provide sufficient exercise dosage (at least
      20 minutes at >= 50% heart rate reserve or total caloric expenditure >= 300
      kilocalories) to induce a cardiorespiratory fitness effect in adults with
      traumatic brain injury? Can feedback from heart rate monitors influence exercise
      intensity? DESIGN: Randomised controlled trial within an observational study.
      PARTICIPANTS: Fifty-three people with severe traumatic brain injury, of whom 40
      progressed into the trial. INTERVENTION: All participants undertook circuit class
      therapy. Participants allocated to the experimental group received exercise
      intensity feedback from a heart rate monitor and the control group received no
      feedback. OUTCOME MEASURES: Proportion of participants exercising at >= 50% heart
      rate reserve for at least 20 minutes or expending >= 300 kilocalories during
      circuit class therapy. The primary outcome measure for the trial was the time
      spent in the heart rate training zone (ie, at >= 50% heart rate reserve) during
      the intervention and re-assessment periods. RESULTS: Circuit class therapy
      provided sufficient cardiorespiratory exercise dosage for 28% (95% CI 18 to 42)
      of the cohort according to the heart rate reserve criteria and 62% (95% CI 49 to
      74) according to the caloric criteria. Feedback did not increase the time in the
      training zone during the intervention (mean difference 4.8 minutes, 95% CI -1.4
      to 10.9) or re-assessment (1.9 minutes, -4.4 to 8.3) periods. CONCLUSION: The low
      intensity, long duration structure of circuit class therapy can provide
      sufficient exercise dosage for a fitness training effect for 62% of people with
      traumatic brain injury. Feedback from heart rate monitors does not necessarily
      influence exercise intensity. TRIAL REGISTRATION: ACTRN12607000522415.

PMID- 22613241
TI  - After total knee arthroplasty, many people are not active enough to maintain
      their health and fitness: an observational study.
AB  - QUESTIONS: What proportion of people after total knee arthroplasty adheres to the
      physical activity regimen recommended for maintenance of health (moderate
      intensity physical activity for at least 30min on 5 days/week)? What proportion
      adheres to the activity regimen recommended to improve fitness (vigorous
      intensity physical activity for at least 20min on 3 days/week)? What factors are
      associated with adherence to these recommendations? DESIGN: An observational
      study. PARTICIPANTS: 830 adults who underwent a total knee arthroplasty between
      2002 and 2006 at University Medical Center Gronigen or Martini Hospital Gronigen,
      the Netherlands. OUTCOME MEASURES: The Short Questionnaire to Assess Health
      Enhancing Physical Activity (SQUASH) was used to measure the physical activity
      behaviour of the participants. These data were analysed as adherence to each
      recommendation. RESULTS: The health recommendation was adhered to by 51% of the
      participants. The fitness recommendation was adhered to by 53% of participants.
      Almost half (46%) of the participants fulfilled both recommendations, and 42% did
      not fulfil either recommendation. Males and more educated participants had higher
      odds of meeting the health, fitness, and both recommendations. Respondents living
      with family had higher odds of meeting the fitness recommendation. CONCLUSION:
      After total knee arthroplasty, 42% of people are not active enough to maintain
      their health and fitness. Physiotherapists should encourage people with a total
      knee arthroplasty to undertake the recommended exercise regimens to maintain
      health and fitness, with particular attention to those people with
      characteristics known to be associated with poor adherence to the
      recommendations.

PMID- 22613242
TI  - Mobility has a non-linear association with falls risk among people in residential
      aged care: an observational study.
AB  - QUESTIONS: What is the association between mobility and falls risk for people
      living in residential aged care? Can the Physical Mobility Scale discriminate
      between residents at risk of falling and those not at risk? DESIGN: Prospective
      longitudinal observational study. SETTING: Six residential aged care facilities
      in Australia. PARTICIPANTS: Eighty-seven high- and low-level care permanent
      residents. OUTCOME MEASURES: The primary outcome measure was the number of falls
      in the six months after the initial mobility assessment. Mobility of all
      participants was assessed using the Physical Mobility Scale, which includes nine
      mobility items assessed on a 0-5 scale yielding a total score out of 45. RESULTS:
      During the six-month study period, 131 falls were reported. Residents with mild
      mobility impairment (Physical Mobility Scale total score 28-36) had the highest
      fall risk (hazard ratio = 1.98, 95% CI 1.30 to 3.03). Residents with fully
      dependent mobility (Physical Mobility Scale total score 0-9) had the lowest risk
      for falls (HR=0.05, 95% CI 0.01 to 0.32). CONCLUSION: Aged care residents with
      mild mobility impairment are at increased risk of falls and are an appropriate
      target for falls prevention strategies. Although improving the mobility of
      residents with moderate to severe mobility impairment may enhance their
      independence and reduce their burden on staff, paradoxically this may also
      increase their risk of falls. When these residents improve enough to progress
      into a higher category of mobility, physiotherapists should be aware that this
      may increase the risk of falls and should consider instituting appropriate falls
      prevention strategies.

PMID- 22613243
TI  - A specific exercise program for patients with subacromial impingement syndrome
      can improve function and reduce the need for surgery.
AB  - QUESTION: Does a specific exercise program improve shoulder function more than
      non-specific exercises in patients with subacromial impingement? DESIGN:
      Randomised, controlled trial with concealed allocation and blinded outcome
      assessment. SETTING: University hospital in Sweden. PARTICIPANTS: Patients aged
      30 to 65 years with subacromial impingement syndrome of at least 6 months
      duration, and on the waiting listing for surgery were included. Key exclusion
      criteria included previous shoulder fractures, and frozen shoulder. Randomisation
      of 102 participants allocated 52 to the intervention exercise group and 50 to a
      control exercise group. INTERVENTIONS: Both groups received a subacromial
      corticosteroid injection at inclusion and commenced exercises 2 weeks later. Both
      groups visited a physiotherapist 7 times over 10 weeks and were prescribed home
      exercises for 12 weeks. The intervention exercise group were prescribed 6
      exercises: 2 eccentric exercises for the rotator cuff, 3 concentric/ eccentric
      exercises for the scapula stabilisers, and a posterior shoulder stretch. Each
      strengthening exercise was repeated 15 times in 3 sets twice daily for 8 weeks
      and then once daily for 4 weeks. The stretch was completed for 30 to 60 seconds
      and repeated 3 times twice daily. Training load was progressed using weights or
      elasticised bands. The control group exercise program consisted of 6 non-specific
      movement exercises for the neck and shoulder (e.g. neck retraction, shoulder
      abduction). The control group exercises were not loaded or progressed and were
      completed 10 times 3 times daily. OUTCOME MEASURES: The primary outcome was the
      Constant shoulder score at 3 months. The Constant score is scored from 0 to 100
      with a higher score indicating better function. Secondary outcome measures
      included the disability of the arm, shoulder and hand questionnaire (DASH), a
      visual analogue score for pain, the EuroQol quality of life instrument, and
      whether the participant thought they still needed surgery. RESULTS: 97
      participants completed the study. At 3 months, the change in Constant score was
      significantly more in the specific exercise group than the control group by 15
      (95% CI 8.5 to 20.6) points. The DASH improved significantly more in the
      intervention than the control group by 8 (95% CI 2.3 to 13.7) points. The
      intervention group also improved significantly more than the control group in
      ratings of night pain, and quality of life. A lower proportion of the specific
      exercise group subsequently chose surgery (20% v 63%, Number Needed to Treat 3,
      95% CI 1.6 to 3.9). CONCLUSION: A specific, progressive exercise program focusing
      on training the rotator cuff and scapular stabilisers was effective in improving
      function, reducing pain and reducing the need of surgery for patients with
      chronic subacromial impingement syndrome. [Numbers needed to treat and 95% CIs
      calculated by the CAP Editor.].

PMID- 22613244
TI  - Daily use of a cane for two months reduced pain and improved function in patients
      with knee osteoarthritis.
AB  - QUESTION: Does daily use of a cane for two months produce clinical benefits in
      patients with knee osteoarthritis (OA)? DESIGN: A randomised, controlled trial
      where group allocation was carried out by computer-generated randomisation in a
      1:1 ratio. SETTING: An outpatient rheumatology clinic in Sao Paulo, Brazil.
      PARTICIPANTS: Men and women with the diagnosis of knee OA according to the
      American College of Rheumatology criteria, knee pain score between 3 and 7 (on a
      0-10 Visual Analogue Scale), stable doses of non-steroidal anti-inflammatory
      drugs (NSAIDs), and no regular physical exercise or use of canes in the months
      prior to the study. Additional exclusion criteria were: symptomatic heart
      disease, symptomatic disease of the lower limbs (other than knee osteoarthritis)
      or of the upper limb that would hold the cane, symptomatic lung disease, severe
      systemic disease, and severe psychiatric illness. INTERVENTIONS: Each participant
      in the intervention group received an individually height adjusted wooden cane
      with a T-shaped handle and instruction in how to use it on the contralateral side
      at the start of the intervention and after one month. They were instructed to use
      the cane daily. The participants in the control group were instructed not use any
      gait device for two months, but otherwise to maintain their normal lives
      including treatment as usual. OUTCOME MEASURES: The primary outcome was pain
      measured on a 0-10 Visual Analogue Scale at one and two months. Secondary
      outcomes were function measured with the Lequesne knee questionnaire and the
      Western Ontario and McMaster Universities (WOMAC) questionnaire), health related
      quality of life (SF-36), energy expenditure during a 6-minute walk test, and
      consumption of NSAIDs. RESULTS: In total 64 patients were assigned to the
      intervention (n=32) and control groups (n=32), and 59 completed the two month
      follow-up. Mean differences in pain were 0.8 (95% CI 0.3 to 1.3) at one month
      follow up and 2.1 (95% CI 1.4 to 2.8) at two months, both in the favour of the
      intervention group. There were significant differences in favour of the
      intervention group in Lequesne knee questionnaire, SF-36 Bodily Pain and Role
      Physical scores, and consumption of NSAIDs. CONCLUSION: Use of a cane can
      diminish pain and improve physical functioning in patients with knee
      osteoarthritis. [95% CIs calculated by the CAP Editors.].

PMID- 22613245
TI  - Combined resistance and aerobic training is more effective than aerobic training
      alone in people with coronary artery disease.
AB  - OBJECTIVE: To review the evidence as to whether combined aerobic and resistance
      training is as effective as aerobic training at improving body composition,
      fitness, strength and quality of life in people with coronary artery disease.
      DATA SOURCES: Cochrane Controlled Trials Register, Embase, Medline, PreMedline,
      SportDiscus and CINAHL, searched up to October 2009. This search was supplemented
      by citation tracking. STUDY SELECTION: Randomised controlled trials involving
      people with coronary artery disease (including people who had undergone coronary
      artery surgery or percutaneous intervention) in which aerobic training was
      compared to combined aerobic and resistance training. Outcome measures were
      measures of cardiovascular fitness, body composition measured by dual energy X
      ray absorptiometry, muscular strength, healthrelated quality of life and self
      efficacy. Trials involving only patients with heart failure were excluded. DATA
      EXTRACTION: Two reviewers determined eligibility and one reviewer extracted data.
      Methodological quality was assessed using the PEDro scale and the Jadad scale.
      DATA SYNTHESIS: Of 271 studies initially identified by the search, 12 studies
      with a total of 504 patients met the selection criteria and were included in the
      review. Study quality ranged from 4 to 8 out of 10 on the PEDro scale, and 2 to 3
      out of 5 on the Jadad scale. Based on the quantitative pooling of the available
      data from these trials, the combined training induced significantly greater
      improvements than aerobic training on most outcomes. Peak exercise capacity was
      better by a standardised mean difference of 0.88 (95% CI 0.45 to 1.31), fat free
      mass improved by 0.9kg more (95% CI 0.4 to 1.4) and percent body fat improved by
      2% more (95% CI 1 to 4). Trunk fat and upper and lower limb strength were also
      significantly better after combined training than after aerobic training. Data
      for quality of life and self efficacy could not be pooled quantitatively, but all
      the studies that measured these outcomes reported improvements either in both
      groups or in the combined training group only. The adverse events noted were
      typically mild cardiovascular changes or musculoskeletal pain. In subgroup
      analyses, the study duration and the intensity of the resistance were not
      associated with an altered treatment effect. CONCLUSION: Combined aerobic and
      resistance training is more effective than aerobic training in improving body
      composition, strength and cardiovascular fitness, probably improving quality of
      life and self efficacy as well.

PMID- 22613246
TI  - Exercise training improves cardiovascular fitness in people receiving
      haemodialysis for chronic renal disease.
AB  - OBJECTIVE: To review the effects of exercise training on cardiovascular fitness,
      cardiac function, strength, quality of life and safety in people on regular
      haemodialysis for chronic renal disease. DATA SOURCES: CENTRAL, Embase, Medline
      and CINAHL, searched up to December 2010. Reference lists of included studies
      were hand searched for further eligible trials. STUDY SELECTION: Randomised
      controlled trials involving people with chronic renal disease on regular
      haemodialysis, in which exercise training was compared to no training or in which
      different exercise modalities were compared. Trials assessing peak oxygen
      consumption as a measure of cardiopulmonary fitness were included. Other outcome
      measures were cardiac function, strength, quality of life, and safety. Exercise
      adherence was also considered. DATA EXTRACTION: : Two reviewers determined the
      eligibility of studies. Methodological quality was assessed using the Jadad
      scale. RESULTS: Of 69 studies initially identified by the searches, 15 studies
      involving a total of 565 participants were eligible and were included in the
      review. Study quality ranged from 1 to 3 out of 5 on the Jadad scale. Eight
      studies involving 365 participants compared cardiovascular fitness between
      training and control groups. The pooled result showed significantly greater peak
      oxygen consumption in the training group by 5mL per kg per min (95% CI 4 to 7).
      Subgroup analyses indicated that this effect was greater among studies where the
      exercise training was of longer duration, was not performed during dialysis, and
      included strength training as opposed to aerobic training alone. The exercise
      group also had significantly lower heart rate variability (ie, heart rate SD
      reduced by 16, 95% CI 8 to 24) and tended to have greater left ventricular
      ejection fraction (by 5%, 95% CI 0 to 9). Two studies measured cross-sectional
      area of limb muscles. Both showed significantly greater improvement in the
      exercise group, but only one also showed significantly greater strength. The
      effect of exercise training on quality of life was not clear, however the
      exercise training appeared to be safe with no deaths reported during exercise
      training. Among those patients originally approached about participation, 25%
      were ineligible due to comorbidities and a further 28% refused to participate. Of
      those who commenced exercise, 15% withdrew, which was similar to the dropout rate
      in the control group. CONCLUSION: Exercise training is safe, substantially
      improves cardiovascular fitness and reduces cardiac variability. To maximise the
      effect on cardiovascular fitness, the training should be longterm, be performed
      outside of haemodialysis periods, and include strength as well as aerobic
      training.

PMID- 22613247
TI  - The Dix-Hallpike Test.

PMID- 22613248
TI  - Active straight leg raise.

PMID- 22613252
TI  - The effects of PTH, loading and surgical insult on cancellous bone at the bone
      implant interface in the rabbit.
AB  - Enhancing the quantity and quality of cancellous bone with anabolic pharmacologic
      agents may lead to more successful outcomes of non-cemented joint replacements.
      Using a novel rabbit model of cancellous bone loading, we examined two specific
      questions regarding bone formation at the bone-implant interface: (1) does the
      administration of intermittent PTH, a potent anabolic agent, and mechanical
      loading individually and combined enhance the peri-implant cancellous bone volume
      fraction; and, (2) does surgical trauma enhance the anabolic effect of PTH on
      peri-implant bone volume fraction. In this model, PTH enhanced peri-implant bone
      volume fraction by 30% in loaded bone, while mechanical loading alone increased
      bone volume fraction modestly (+10%). Combined mechanical loading and PTH
      treatment had no synergistic effect on any cancellous parameters. However, a
      strong combined effect was found in bone volume fraction with combined surgery
      and PTH treatment (+34%) compared to intact control limbs. Adaptive changes in
      the cancellous bone tissue included increased ultimate stress and enhanced
      remodeling activity. The number of proliferative osteoblasts increased as did
      their expression of pro-collagen 1 and PTH receptor 1, and the number of TRAP
      positive osteoclasts also increased. In summary, both loading and intermittent
      PTH treatment enhanced peri-implant bone volume, and surgery and PTH treatment
      had a strong combined effect. This finding is of clinical importance since
      enhancing early osseointegration in the post-surgical period has numerous
      potential benefits.

PMID- 22613253
TI  - Identification of Streptococcus equi ssp. zooepidemicus surface associated
      proteins by enzymatic shaving.
AB  - Streptococcus equi ssp. zooepidemicus (Streptococcus zooepidemicus, SEZ) is
      responsible for a wide variety of infections in many species. Attempts to control
      the infection caused by this agent are hampered by a lack of effective vaccines
      and useful diagnostic kits. Surface proteins of bacterial species are usually
      involved in interaction with host and hopefully act as biomarkers for
      serodiagnosis and subunit vaccine components. In this study, the surface proteins
      of SEZ C55138 strain were systematically identified by surface shaving with
      trypsin and a total of 20 surface associated proteins were found. Further
      analysis of five selected novel proteins (SzM, FBP, SAP, CSP and 5'-Nu) revealed
      that they all expressed in vivo and their recombinant derived proteins could be
      reactive with convalescent sera. These identified immunogenic surface proteins
      have potential as SEZ vaccine candidates and diagnostic markers.

PMID- 22613254
TI  - High prevalence of bovine viral diarrhea virus 1 in Chinese swine herds.
AB  - Nested RT-PCR was used to investigate bovine viral diarrhea virus in 511
      specimens collected from Chinese pigs exhibiting clinical symptoms between 2007
      and 2010. Of these, 137 samples were BVDV-positive and the BVDV prevalence rate
      was 23.1% (9/39) in 2007, 27.7% (44/159) in 2008, 33.6% (34/101) in 2009, and
      23.6% (50/212) in 2010. Twenty of 137 BVDV-positive samples were used for further
      genetic analysis of the 5'-UTR. Phylogenetic analysis revealed that they were
      BVDV-1 and subtyped into BVDV-1a, BVDV-1b, BVDV-1m, BVDV-1o and an unknown
      subgenotype. This study showed that BVDVs were highly prevalent in Chinese pig
      herds and appropriate measures should be taken to control BVDV prevalence in pig
      herds.

PMID- 22613256
TI  - Cholesterol-5,6-epoxides: chemistry, biochemistry, metabolic fate and cancer.
AB  - In the nineteen sixties it was proposed that cholesterol might be involved in the
      etiology of cancers and cholesterol oxidation products were suspected of being
      causative agents. Researchers had focused their attention on cholesterol-5,6
      epoxides (5,6-ECs) based on several lines of evidence: 1) 5,6-ECs contained an
      oxirane group that was supposed to confer alkylating properties such as those
      observed for aliphatic and aromatic epoxides. 2) cholesterol-5,6-epoxide
      hydrolase (ChEH) was induced in pre-neoplastic lesions of skin from rats exposed
      to ultraviolet irradiations and ChEH was proposed to be involved in
      detoxification processes like other epoxide hydrolases. However, 5,6-ECs failed
      to induce carcinogenicity in rodents which ruled out a potent carcinogenic
      potential for 5,6-ECs. Meanwhile, clinical studies revealed an anomalous increase
      in the concentrations of 5,6beta-EC in the nipple fluids of patients with pre
      neoplastic breast lesions and in the blood of patients with endometrious cancers,
      suggesting that 5,6-ECs metabolism could be linked with cancer. Paradoxically,
      ChEH has been recently shown to be totally inhibited by therapeutic
      concentrations of tamoxifen (Tam), which is one of the main drugs used in the
      hormonotherapy and the chemoprevention of breast cancers. These data would
      suggest that the accumulation of 5,6-ECs could represent a risk factor, but we
      found that 5,6-ECs were involved in the induction of breast cancer cell
      differentiation and death induced by Tam suggesting a positive role of 5,6-ECs.
      These observations meant that the biochemistry and the metabolism of 5,6-ECs
      needed to be extensively studied. We will review the current knowledge and the
      future direction of 5,6-ECs chemistry, biochemistry, metabolism, and relationship
      with cancer.

PMID- 22613257
TI  - Prioritising health in anti-doping: what Australians think.
AB  - OBJECTIVES: There is debate concerning whether the guiding paradigm for anti
      doping policy should be the current legalistic approach or a "harm minimisation"
      approach prioritising athlete health. This study sought to determine whether a
      representative sample of Australians prioritises health above other concerns
      using the World Anti-Doping Code's Spirit of Sport statement which lists the 11
      attributes that define the moral basis for anti-doping. DESIGN: A Best-Worst
      Scaling (BWS) Balanced Incomplete Block Design experiment using 11 choice sets of
      five Spirit attributes from the set of 11, with the attributes within each choice
      set in a random order. METHODS: A representative sample of n=168 Australians
      responded to an on-line survey. The BWS scores defined the relative ranking of
      each attribute to define an aggregate model and demographically defined models
      (gender, education, sports participation and sports following). RESULTS: Health
      was ranked as 7/11 in the aggregate model. Only those who did not follow sport
      prioritised health (2/11), with other demographic models failing to show a
      meaningful departure from the aggregate model. CONCLUSIONS: Australians ranked
      health below other attributes in the Spirit of Sport, appearing to prioritise
      "rule following" consistent with the legalistic approach. This challenges the
      harm minimisation approach to managing the role of drugs in sport and suggests
      that rule-following and legalistic approaches to drug use should take precedence
      over health messages.

PMID- 22613255
TI  - Increased marijuana use and gender predict poorer cognitive functioning in
      adolescents and emerging adults.
AB  - This study sought to characterize neuropsychological functioning in MJ-using
      adolescents and emerging adults (ages 18-26) and to investigate whether gender
      moderated these effects. Data were collected from 59 teens and emerging adults
      including MJ users (n = 23, 56% female) and controls (n = 35, 50% female) aged 18
      26 (M = 21 years). Exclusionary criteria included independent Axis I disorders
      (besides SUD), and medical and neurologic disorders. After controlling for
      reading ability, gender, subclinical depressive symptoms, body mass index, and
      alcohol and other drug use, increased MJ use was associated with slower
      psychomotor speed/sequencing ability (p < .01), less efficient sustained
      attention (p < .05), and increased cognitive inhibition errors (p < .03). Gender
      significantly moderated the effects of MJ on psychomotor speed/sequencing ability
      (p < .003) in that males had a more robust negative relationship. The current
      study demonstrated that MJ exposure was associated with poorer psychomotor speed,
      sustained attention and cognitive inhibition in a dose-dependent manner in young
      adults, findings that are consistent with other samples of adolescent MJ users.
      Male MJ users demonstrated greater cognitive slowing than females. Future studies
      need to examine the neural substrates underlying with these cognitive deficits
      and whether cognitive rehabilitation or exercise interventions may serve as a
      viable treatments of cognitive deficits in emerging adult MJ users.

PMID- 22613258
TI  - Electrophysiological indices of biased cognitive processing of substance-related
      cues: a meta-analysis.
AB  - Several studies indicate that individuals with substance use disorders (SUD)
      exhibit biases in the cognitive processing of substance-related stimuli. These
      biases facilitate the detection of substance cues and have been argued to play a
      causal or perpetuating role in addiction. Two electrophysiological indices of
      cognitive processing, the P300 and Slow Potential (SP) components of the event
      related potential (ERP), are associated with the deployment of attentional
      resources to motivationally relevant stimuli. In the present meta-analysis P300
      (300-800ms) and SP (>800ms) amplitudes are used to investigate whether SUD
      persons show enhanced cognitive processing of substance cues relative to neutral
      cues as opposed to control participants. Results indicated the P300 and SP
      amplitude effect sizes were significantly larger in SUD participants than
      controls. This result is explained by substance users' motivated attention.
      Additional stratified moderator analyses revealed that both P300 and SP
      amplitudes were not moderated by electrode site (Fz vs. Pz), type of substance
      used (stimulants vs. depressants), substance use status (abstinent vs. non
      abstinent), age, gender and task requirements (active vs. passive paradigms).

PMID- 22613259
TI  - Incidence of diabetic retinopathy in Bangladesh: a 15-year follow-up study.
AB  - BACKGROUND: The aim of the present study was to estimate the incidence of
      diabetic retinopathy (DR) among type 2 diabetic (T2D) subjects in Bangladesh.
      METHODS: A random sample of 977 patients with T2D was recruited retrospectively
      in 2008 from newly diagnosed T2D patients who had attended the Bangladesh
      Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic
      Disorder (BIRDEM) in 1993. Baseline information for the cohort was collected for
      1993 from hospital records. The mean time until development of DR in newly
      diagnosed T2D patients was calculated using survival analysis. Cox's proportional
      hazards model was used to assess factors affecting the time until development of
      DR. RESULTS: The cumulative incidence of DR over the 15-year period was 50.6%
      (95% confidence interval [CI] 47.5%-53.8%). The incidence density (per 100 person
      years) of DR was similar in the overall cohort (4.1; 95% CI 3.7-4.5) and in men
      (4.2; 95% CI 3.7-4.7) and women (4.1; 95% CI 3.6-4.6) separately. The mean time
      (in years) until development of DR in the cohort was 9.72 (95% CI 9.38-10.06),
      with similar times in men (9.8; 95% CI 9.3-10.3) and women (9.6; 95% CI 9.5-10.1)
      analyzed separately. Age, sex, hypertension, lipid profile, HbA1c, and serum
      creatinine were entered into the hazards model simultaneously. However, only age
      (hazard ratio [HR] 0.75; 95% CI 0.61-0.92) and HbA1c (HR 0.52; 95% CI 0.33-0.82)
      had a significant effect on the time until development of DR. CONCLUSIONS:
      Glucose deregulation is the most important factor in the development of DR.

PMID- 22613260
TI  - Chance between holism and reductionism: tensions in the conceptualisation of
      Life.
AB  - In debates between holism and reductionism in biology, from the early twentieth
      century to more recent re-enactments involving genetic reductionism,
      developmental systems theory or systems biology, the role of chance - the
      presence of theories invoking chance as a strong explanatory principle - is
      hardly ever acknowledged. Conversely, Darwinian models of chance and selection
      (Dennett, 1995; Kupiec, 1996, 2009) sit awkwardly with reductionist and holistic
      concepts, which they alternately challenge or approve of. I suggest that the
      juxtaposition of chance and the holism-reductionism pair (at multiple levels,
      ontological and methodological, pertaining to the vision of scientific practice
      as well as to the foundations of a vision of Nature, implicit or explicit) allows
      the theorist to shed some new light on these perennial tensions in the
      conceptualisation of Life.

PMID- 22613261
TI  - Production of truncated protein by the crosslink formation of mRNA with 2'-OMe
      oligoribonucleotide containing 2-amino-6-vinylpurine.
AB  - The development of convenient methods for controlling the protein expression is
      an important challenge in the postgenomic era. We applied the crosslink forming
      oligonucleotide (CFO) as a terminator of the ribosomal translation. In this
      study, we demonstrated that the improved reactivity of our CFO under
      physiological conditions enabled the sequence-specific introduction of a steric
      block for a ribosome on mRNAs. In vitro and in cell translation experiments
      revealed that the crosslinked mRNA can produce the truncated proteins in which
      the translation terminates at the desired position.

PMID- 22613263
TI  - Unusual discrepancy between S(pO(2)) and S(aO(2)) in a 31-year-old man with
      chronic myelogenous leukemia.

PMID- 22613264
TI  - Glycemic index and glycemic load in relation to glucose intolerance among
      Greenland's Inuit population.
AB  - BACKGROUND: Intake of carbohydrates which elicit a large glycemic response is
      hypothesized to increase the risk of diabetes. However, studies assessing the
      relationship between glycemic index (GI) and glycemic load (GL) and diabetes are
      inconsistent. Only few studies have studied the relationship between GI and GL
      and markers of glucose metabolism, mostly in western populations. OBJECTIVE: To
      determine the relationship between GI and GL and indices of glucose metabolism
      and prevalence of diabetes in Greenland's Inuit population. DESIGN: The Inuit
      Health in Transition Study is a geographically representative cross-sectional
      study among aged >=18years. Diet was assessed using a 67-item food frequency
      questionnaire. Logistic and linear regression was used to assess the association
      between GI and GL and diabetes, impaired fasting glucose, impaired glucose
      tolerance, HbA(1c), fasting plasma glucose, 2h plasma glucose, HOMA2-IR and HOMA2
      %beta. RESULTS: No association was found between GI and GL and diabetes. GL was
      significantly inversely associated with IFG (OR: 0.91 (0.84-0.98)). While GI was
      positively associated with FPG, GL was positively associated with both HOMA2-IR
      and HOMA2-%beta and inversely associated with IFG. CONCLUSION: These findings do
      not support a link between dietary GI or GL and risk of type 2 diabetes among
      Greenland's Inuit population.

PMID- 22613262
TI  - 8-Oxo-2'-deoxyguanosine as a biomarker of tobacco-smoking-induced oxidative
      stress.
AB  - 7,8-Dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dGuo) is a useful biomarker of
      oxidative stress. However, its analysis can be challenging because 8-oxo-dGuo
      must be quantified in the presence of dGuo, without artifactual conversion to 8
      oxo-dGuo. Urine is the ideal biological fluid for population studies, because it
      can be obtained noninvasively and it is less likely that artifactual oxidation of
      dGuo can occur because of the relatively low amounts that are present compared
      with hydrolyzed DNA. Stable isotope dilution liquid chromatography-selected
      reaction monitoring/mass spectrometry (LC-SRM/MS) with 8-oxo-[(15)N(5)]dGuo as
      internal standard provided the highest possible specificity for 8-oxo-dGuo
      analysis. Furthermore, artifact formation was determined by addition of
      [(13)C(10)(15)N(5)]dGuo and monitoring of its conversion to 8-oxo
      [(13)C(10)(15)N(5)]dGuo during the analytical procedure. 8-Oxo-dGuo
      concentrations were normalized for interindividual differences in urine flow by
      analysis of creatinine using stable isotope dilution LC-SRM/MS. A significant
      increase in urinary 8-oxo-dGuo was observed in tobacco smokers compared with
      nonsmokers either using simple urinary concentrations or after normalization for
      creatinine excretion. The mean levels of 8-oxo-dGuo were 1.65ng/ml and the levels
      normalized to creatinine were 1.72MUg/g creatinine. Therefore, stable isotope
      dilution LC-SRM/MS analysis of urinary 8-oxo-dGuo complements urinary isoprostane
      (isoP) analysis for assessing tobacco-smoking-induced oxidative stress. This
      method will be particularly useful for studies that employ polyunsaturated fatty
      acids, in which a reduction in arachidonic acid precursor could confound isoP
      measurements.

PMID- 22613265
TI  - Do triglycerides interfere with the determination of haemoglobin A1c? History of
      a fallacy.

PMID- 22613266
TI  - Mobile diabetes eye care: experience in developing countries.
AB  - The prevalence of diabetes in developing countries is on the increase and along
      with it the need to provide structured care to avoid the feared long term
      complications among them loss of vision and blindness due to diabetic retinopathy
      (DR). The biggest hurdle facing most developing countries is the lack of
      resources and trained manpower to both screen and treat the large number of
      people with DR. Countries also face the additional problem of unequal
      distribution of resources between the urban and rural areas. To overcome these
      challenges models of mobile diabetic retinopathy screening and treatment aided by
      the use of telemedicine have been introduced and demonstrated to be popular and
      effective. The aim of this review article is to describe different mobile
      diabetic retinopathy screening and treatment models developed in India, which can
      be readily replicated in developing countries presented with similar
      difficulties.

PMID- 22613267
TI  - Detection of a novel splicing mutation causing analbuminemia in a Libyan family.
AB  - BACKGROUND AND OBJECTIVES: Analbuminemia is a very rare autosomal recessive
      disorder. It is an allelic heterogeneous defect caused by a variety of mutations
      within the albumin gene. We describe in this report two new cases of
      analbuminemia in Libyans. DESIGN AND METHODS: The 14 coding exons of the human
      serum albumin (HSA) gene and their intron-exon junctions were PCR amplified. The
      products were screened for mutations by Denaturing High Performance Liquid
      Chromatography (DHPLC). Samples with altered DHPLC profiles were sequenced.
      RESULTS: DNA sequencing revealed the presence of a novol homozygous G?T
      transition in the first base of intron 11 (c.1428+1G>T), in both children. This
      mutation destroys the GT consensus donor sequence found at the 5' end of most
      intervening sequences and would cause the defective pre-mRNA splicing.
      CONCLUSION: Molecular diagnosis based on DHPLC and DNA sequencing represents a
      powerful tool to study molecular defects causing analbuminemia.

PMID- 22613268
TI  - Distinguishing pancreatic cancer from chronic pancreatitis and healthy
      individuals by (1)H nuclear magnetic resonance-based metabonomic profiles.
AB  - OBJECTIVES: To develop a noninvasive and accessible diagnostic method for
      pancreatic cancer (PC). DESIGN AND METHODS: We presented a metabolomic method,
      pattern recognition techniques applied to (1)H nuclear magnetic resonance ((1)H
      NMR) spectra, to investigate the plasma metabolites obtained from 19 patients
      with PC, 20 patients with chronic pancreatitis (CP) and 20 healthy individuals.
      RESULTS: Metabolic changes associated with PC included abnormal amino acid and
      lipid metabolism, and possible multiple metabolic syndrome. PC elevated plasma
      levels of N-acetyl glycoprotein (NAG), dimethylamine (DMA), very low density
      lipoprotein (VLDL), and acetone, and reduced levels of 3-hydroxybutyrate,
      lactate, high density lipoprotein (HDL), low density lipoprotein (LDL), citrate,
      alanine, glutamate, glutamine, histidine, isoleucine, lysine, and valine. These
      metabolites could be a biomarker group for PC that distinguishes between PC and
      CP patients and healthy individuals. CONCLUSIONS: NMR-based metabonomic strategy
      appears as a promising approach for distinguishing pancreatic cancer and
      identifying new strategies for prevention or therapy in the clinical practice.

PMID- 22613270
TI  - Genetic variation for stress-response hormesis in C. elegans lifespan.
AB  - Increased lifespan can be associated with greater resistance to many different
      stressors, most notably thermal stress. Such hormetic effects have also been
      found in C. elegans where short-term exposure to heat lengthens the lifespan.
      Genetic investigations have been carried out using mutation perturbations in a
      single genotype, the wild type Bristol N2. Yet, induced mutations do not yield
      insight regarding the natural genetic variation of thermal tolerance and
      lifespan. We investigated the genetic variation of heat-shock recovery, i.e.
      hormetic effects on lifespan and associated quantitative trait loci (QTL) in C.
      elegans. Heat-shock resulted in an 18% lifespan increase in wild type CB4856
      whereas N2 did not show a lifespan elongation. Using recombinant inbred lines
      (RILs) derived from a cross between wild types N2 and CB4856 we found natural
      variation in stress-response hormesis in lifespan. Approx. 28% of the RILs
      displayed a hormesis effect in lifespan. We did not find any hormesis effects for
      total offspring. Across the RILs there was no relation between lifespan and
      offspring. The ability to recover from heat-shock mapped to a significant QTL on
      chromosome II which overlapped with a QTL for offspring under heat-shock
      conditions. The QTL was confirmed by introgressing relatively small CB4856
      regions into chromosome II of N2. Our observations show that there is natural
      variation in hormetic effects on C. elegans lifespan for heat-shock and that this
      variation is genetically determined.

PMID- 22613269
TI  - Comparison of oral and intravenous Ibuprofen for medical closure of patent ductus
      arteriosus: which one is better?
AB  - OBJECTIVE: Intravenous ibuprofen is an expensive drug that is being used
      currently for treating and preventing patent ductus arteriosus. Although oral
      ibuprofen is much cheaper, there is limited data published about its safety and
      efficacy. The aim of this study was to compare two forms of ibuprofen in terms of
      safety and efficacy in closure of patent ductus arteriosus. DESIGN: This is a
      single-center retrospective study. SETTING: Data were collected from patients'
      files of preterm infants who were hospitalized at the Neonatal Intensive Care
      Unit of Dr. Behcet Uz Children's Hospital between April 2009 and June 2010.
      PATIENTS: Six hundred sixty infants were evaluated by echocardiography between 24
      and 48 postnatal hours. Clinically and hemodynamically significant ductus
      arteriosus was defined in 66 infants with gestational age less than 32 weeks and
      birth weight less than 1500 g. INTERVENTIONS: Oral or intravenous ibuprofen
      (loading dose: 10 mg/kg on day 1, followed by maintenance dose: 5 mg/kg on days 2
      and 3) was administered. OUTCOME MEASURES: Treatment success was defined as a
      completely closed duct without reopening on follow-up. Drug-associated renal,
      gastrointestinal, cerebral, hematological, and metabolic side effects were
      monitored and compared between treatment groups. RESULTS: Ductal closure rates
      were 100% and 97.6%, respectively, in the oral and intravenous groups.
      Hypernatremia was the remarkable side effect in the intravenous group, whereas
      bronchopulmonary dysplasia and septicemia were prominent in the oral group. No
      statistically significant difference could be demonstrated between the groups in
      terms of mortality rates. CONCLUSION: Oral ibuprofen therapy is as efficacious as
      intravenous ibuprofen with some concerns about increased sepsis and
      bronchopulmonary dysplasia incidence. However, comprehensive and large-scale
      pharmacokinetic studies are required in order to prove this efficacy. On the
      other hand, intravenous ibuprofen still remains to be the drug of choice for
      patent ductus arteriosus but only with meticulous control of serum sodium levels
      in smaller infants.

PMID- 22613271
TI  - Efficacy and safety of high dose intramuscular or oral cholecalciferol in vitamin
      D deficient/insufficient elderly.
AB  - OBJECTIVES: To evaluate and compare the effects and safety of high dose
      intramuscular (IM) or oral cholecalciferol on 25-hydroxyvitamin D [25(OH)D]
      levels, muscle strength and physical performance in vitamin D
      deficient/insufficient elderly. STUDY DESIGN: Randomized prospective study. MAIN
      OUTCOME MEASURES: 116 ambulatory individuals aged 65 years or older living in a
      nursing home were evaluated. Eligible patients with 25(OH)D levels <30 ng/ml
      (n=66) were randomized to IM or Oral groups according to the administration route
      of 600,000 IU cholecalciferol. Demographic and descriptive data were collected.
      Biochemical response was measured at baseline, 6th and 12th weeks. Muscle
      strength was measured from quadriceps by using a hand-held dynamometer and
      physical performance was evaluated by short physical performance battery (SPPB)
      at the beginning and 12th week. RESULTS: Among the screened ambulatory elderly
      only 5.2% (n=6) had adequate vitamin D levels. 37.1% (n=43) were vitamin D
      deficient and 57.7% (n=67) were insufficient. After administration of one
      megadose of vitamin D, mean serum 25(OH)D levels increased significantly at 6th
      week (32.72+/-9.0 ng/ml) and at 12th week (52.34+/-14.2 ng/ml) compared with
      baseline (11.76+/-7.6 ng/ml) in IM group (p<0.0001). In Oral group levels were
      47.57+/-12.7 ng/ml, 42.94+/-13.4 ng/ml and 14.87+/-6.9 ng/ml, respectively
      (p<0.0001). At 12th week the increase in IM group was significantly higher than
      Oral group (p=0.003). At the end of the study period, serum 25(OH)D levels were
      >=30 ng/ml in all patients in IM group and in 83.3% of the patients in the Oral
      group. Quadriceps muscle strength and SPPB total score increased significantly in
      both groups and SPPB balance subscale score increased only in IM group. Six
      patients (9.6%) developed hypercalciuria, no significant adverse events were
      observed. CONCLUSION: In vitamin D deficient/insufficient elderly, a single
      megadose of cholecalciferol increased vitamin D levels significantly and the
      majority of the patients reached optimal levels. Although both administration
      routes are effective and appear to be safe, IM application is more effective in
      increasing 25(OH)D levels and balance performance.

PMID- 22613272
TI  - Cognitive and prepulse inhibition deficits in psychometrically high schizotypal
      subjects in the general population: relevance to schizophrenia research.
AB  - Schizophrenia and schizotypal personality disorder share common clinical
      profiles, neurobiological and genetic substrates along with Prepulse Inhibition
      and cognitive deficits; among those, executive, attention, and memory
      dysfunctions are more consistent. Schizotypy is considered to be a non-specific
      "psychosis-proneness," and understanding the relationship between schizotypal
      traits and cognitive function in the general population is a promising approach
      for endophenotypic research in schizophrenia spectrum disorders. In this review,
      findings for executive function, attention, memory, and Prepulse Inhibition
      impairments in psychometrically defined schizotypal subjects have been summarized
      and compared to schizophrenia patients and their unaffected first-degree
      relatives. Cognitive flexibility, sustained attention, working memory, and
      Prepulse Inhibition impairments were consistently reported in high schizotypal
      subjects in accordance to schizophrenia patients. Genetic studies assessing the
      effects of various candidate gene polymorphisms in schizotypal traits and
      cognitive function are promising, further supporting a polygenic mode of
      inheritance. The implications of the findings, methodological issues, and
      suggestions for future research are discussed.

PMID- 22613273
TI  - Teaching basic life support to children using a humorous video.

PMID- 22613274
TI  - Non-invasive monitoring and cardiac arrest: a cautious attempt to view beyond the
      curtain (skin).

PMID- 22613275
TI  - Maternal cardiac arrest and perimortem caesarean delivery: evidence or expert
      based?
AB  - AIM: To examine the outcomes of maternal cardiac arrest and the evidence for the
      4-min time frame from arrest to perimortem caesarean delivery (PMCD) recommended
      in current resuscitation and obstetric guidelines. DATA SOURCES AND METHODS:
      Review and data extraction from all reported maternal cardiac arrests occurring
      prior to delivery (1980-2010). Cases were included if they provided details
      regarding both the event and outcomes. Outcomes of arrest were assessed using
      survival, Cerebral Performance Category (CPC) and maternal/neonatal harm/benefit
      from PMCD. Outcome measures were maternal and neonatal survival. RESULTS: Of 1594
      manuscripts screened, 156 underwent full review. Data extracted from 80 relevant
      papers yielded 94 included cases. Maternal outcome: 54.3% (51/94) of mothers
      survived to hospital discharge, 78.4% (40/51) with a CPC of 1/2. PMCD was
      determined to have been beneficial to the mother in 31.7% of cases and was not
      harmful in any case. In-hospital arrest and PMCD within 10 min of arrest were
      associated with better maternal outcomes (ORs 5.17 and 7.42 respectively, p<0.05
      both). Neonatal outcome: mean times from arrest to delivery were 14+/-11 min and
      22+/-13 min in survivors and non-survivors respectively (receiver operating area
      under the curve 0.729). Neonatal survival was only associated with in-hospital
      maternal arrest (OR 13.0, p<0.001). CONCLUSIONS: Treatment recommendations should
      include a low admission threshold to a highly monitored area for pregnant women
      with cardiorespiratory decompensation, good overall performance of resuscitation
      and delivery within 10 min of arrest. Cognitive dissonance may delay both
      situation recognition and the response to maternal collapse.

PMID- 22613276
TI  - Lymphoid tissue structure and HIV-1 infection: life or death for T cells.
AB  - Secondary lymphoid tissue (LT) structure facilitates immune responses and
      maintains homeostasis of T cells through production of survival factors, such as
      interleukin (IL)-7 that is 'posted' on the stromal fibroblastic reticular cell
      (FRC) network on which T cells traffic. Here, we examine the pathological changes
      that occur in LTs during HIV and simian immunodeficiency virus (SIV) infection.
      Immune activation leads to collagen deposition and loss of the FRC network
      itself. This decreases access to IL-7 and reduces the major source of IL-7, both
      of which deplete naive T cells to limit immune reconstitution with antiretroviral
      treatment. We discuss the implications of LT structure damage for the timing of
      antiretroviral therapy and consider the development of adjunctive antifibrotic
      agents to improve immune reconstitution in HIV infection.

PMID- 22613277
TI  - The impact of antibodies in late-onset Pompe disease: a case series and
      literature review.
AB  - Pompe disease (glycogen storage disease type II, GSD II) is an autosomal
      recessive disease caused by a deficiency of acid alpha-glucosidase (GAA), leading
      to lysosomal glycogen accumulation in various tissues, most notably cardiac,
      skeletal and smooth muscle. While both infantile and late-onset patients have
      benefited greatly from alglucosidase alfa (Myozyme(r)) enzyme replacement therapy
      (ERT), a subgroup of patients does not demonstrate as pronounced a response as
      others. Various factors have been identified which may help predict the response
      to ERT in infantile Pompe disease patients. High, sustained antibody titers
      (HSAT) have been correlated with poor response to ERT in infantile Pompe cases.
      However, the literature on the role of antibodies in the late-onset Pompe disease
      (LOPD) population is limited. Our literature review highlights the need for
      studies to explore the potential impact of antibodies in LOPD. Further supporting
      the importance of this issue, our retrospective chart review of sixty LOPD
      patients revealed that six of these sixty (10%) LOPD patients developed HSAT of
      >=1:51,200 on two or more occasions at or beyond 6 months on ERT. Here, we
      present a series of three of these six LOPD patients for whom detailed antibody
      data and clinical data were available for greater than 1 year on ERT. These three
      patients developed HSAT corresponding with clinical decline as demonstrated by
      pulmonary function, quality of life, and motor function testing, affirming the
      development of HSAT in a subset of patients with LOPD, and its potentially
      negative impact on clinical response to ERT. The findings of our study and
      literature review lead us to conclude that there is a strong indication for
      systematic studies to accurately delineate the potential impact of antibodies in
      LOPD.

PMID- 22613278
TI  - Adenoid cystic carcinoma of the breast: case report and review of literature.
AB  - We report the case of a patient who presented with a painful breast lump that
      turned out to be an adenoid cystic carcinoma of the breast. The literature is
      reviewed, highlighting the good prognosis associated with this rare condition and
      the current preferred treatment modalities.

PMID- 22613280
TI  - Primary extraskeletal Ewing sarcoma involving the carotid artery: a case report
      and review of the current literature.
AB  - Extraskeletal Ewing sarcoma (EES) is a rare soft tissue neoplasm of primitive
      mesenchymal cells. There is a scarcity of data on EES involving the head and
      neck, with studies being over years or even decades. We are the first to report a
      case of EES involving the carotid artery and its subsequent surgical excision and
      reconstruction.

PMID- 22613279
TI  - Local anaesthetic surgical treatment of severe objective pulsatile tinnitus: a
      useful technique.
AB  - Objective pulsatile tinnitus is a rare condition with an often dramatic
      presentation. We present the case of a 70-year-old woman who presented with over
      two years' history of unilateral distressing objective pulsatile tinnitus.
      Carotid arteriography revealed a highly tortuous internal carotid artery.
      Computed tomography of the ipsilateral temporal bones showed a large jugular
      bulb. Internal jugular vein ligation under local anaesthetic yielded immediate
      resolution of her symptoms.

PMID- 22613281
TI  - A perforated duodenal ulcer presenting as inferior lead ST elevation following
      amphetamine use.
AB  - Typical symptoms of duodenal ulcers include epigastric pain, nausea, vomiting,
      chest pain and shortness of breath. Here we present the case of a 39-year-old man
      who had a sudden onset of chest and epigastric pain following the use of
      recreational amphetamines. There were ST changes in the inferior leads of his
      electrocardiogram, indicating the possibility of a myocardial infarction.
      Following double contrast computed tomography of the abdomen and an urgent
      laparotomy, a diagnosis of a perforated duodenal ulcer was made. We discuss the
      aetiologies, presentation, investigation and treatment of the disorder, and make
      recommendations on the management.

PMID- 22613282
TI  - Primary angiosarcoma of the larynx: a rare entity.
AB  - Angiosarcomas are extremely rare malignant tumours of the larynx. We present a
      case of laryngeal angiosarcoma in a 58-year-old man who presented with hoarseness
      of voice, dysphagia and neck swelling. The patient underwent a total laryngectomy
      with a pre-operative and frozen section diagnosis of a poorly differentiated
      carcinoma of the larynx. Histopathological and immunohistochemical evaluation
      revealed features of a laryngeal angiosarcoma. The case is presented for its
      rarity and diagnostic difficulty.

PMID- 22613284
TI  - Urinary tract transitional cell carcinoma and melanosis of the bladder: a case
      report and review of the literature.
AB  - Melanosis vesica is a rare condition and thought to be benign. We report the case
      of a 50-year-old man who presented with haematuria and was found to have a
      diffusely pigmented bladder on cystoscopy and high grade transitional cell
      carcinoma of his upper and lower renal tract. This required a laparoscopic
      nephroureterectomy and pathology confirmed a diagnosis of melanosis vesica.
      Melanosis vesica has only been associated with high grade transitional cell
      carcinoma in one previous case. We recommend that any patient presenting with
      bladder melanosis is monitored for the development of upper or lower urinary
      tract transitional cell carcinoma.

PMID- 22613283
TI  - The oldest reported mirror hand? The curse of the coal-house frog!
AB  - Despite being one of the rarest congenital upper limb abnormalities, a wide
      spectrum of the typical mirror hand has been described in the literature. We
      report a very interesting case of a new variant of mirror hand presenting in a 78
      year-old man. The unique features of the case include  the age at diagnosis, the
      anatomical features present and the acquired function despite no form of
      reconstructive surgery.

PMID- 22613285
TI  - Bilateral lower limb compartment syndrome: a potentially destructive complication
      of breast reduction.
AB  - Compartment syndrome is a serious condition in which the pressure in the limb
      increases and potentially compromises capillary circulation with subsequent
      ischaemic complications. This case report presents a case of bilateral lower limb
      compartment syndrome after bilateral breast reduction  for back pain. The patient
      was an otherwise healthy 24-year-old Afro-Caribbean woman. This report aims to
      highlight the need for an increased index of suspicion for compartment syndrome
      in any postoperative patient complaining of lower limb pain.

PMID- 22613286
TI  - Transnasal K-wire to stabilise a complex zygomatic fracture: a forgotten method
      of fixation.
AB  - Zygomatic complex fractures make up approximately 60% of facial fractures. The
      vast majority treated surgically use titanium miniplates. These require longer
      operating times and facial incisions to access the fracture. The use of a K-wire
      was first described 60 years ago. As a new generation  of surgeons emerges, it is
      important to be aware of the various techniques available to increase their
      surgical armamentarium. One of its benefits is that it has a significantly
      reduced operative time and does not require any incisions.

PMID- 22613288
TI  - Curtain gastroplasty as an option in high risk emergency hiatus hernia repair.
AB  - INTRODUCTION: We describe a novel surgical technique used in the case of an 86
      year-old Caucasian man with multiple comorbidities who presented with upper
      intestinal obstruction caused by a large paraoesophageal hiatus hernia and
      concurrent urinary sepsis. METHODS: The technique,  which minimises both
      operative time and surgical trauma in this situation, uses the fundus of the
      stomach in a modified Dor anterior fundoplication as a gastric fundoplasty to
      close the defect. The total operative time was 70 minutes. RESULTS: The patient's
      recovery was complicated by  a lower respiratory tract infection but he was
      discharged 14 days after surgery with a premorbid oral intake and activity level.
      CONCLUSIONS: We believe this curtain gastroplasty technique represents another
      surgical option to reduce operative time and trauma in a subgroup of high risk 
      patients presenting with life threatening complications of a large hiatus hernia
      who have limited physiological reserve and evidence of current ongoing sepsis.

PMID- 22613287
TI  - A case report of anaphylaxis to chlorhexidine during urinary catheterisation.
AB  - Chlorhexidine gluconate is a chemical antiseptic that is effective against Gram
      positive and negative bacteria and on certain viruses and fungi. A bacteriocidal
      and bacteriostatic agent, this cationic drug is absorbed on to negatively charged
      cell surfaces of organisms, disrupting the  cell membrane, which results in
      increased permeability. Its use is mainly topical as a surgical hand antisepsis,
      site preparation/cleansing and for pre-genitourinary procedures such as urethral
      catheterisation. Like any drug, caution should be employed with its use as
      hypersensitivity reactions  are being documented increasingly in the medical
      literature. In the following case, we present a patient who was catheterised with
      the chlorhexidine containing Instillagel((r)) (CliniMed, High Wycombe, UK), prior
      to undergoing elective orthopaedic surgery.

PMID- 22613289
TI  - Spontaneous liver haemorrhage and haemobilia as initial presentation of
      undiagnosed polyarteritis nodosa.
AB  - Polyarteritis nodosa (PAN) is a systemic necrotising vasculitis that could result
      in multifocal aneurysms of visceral arteries. Isolated multiple aneurysms of the
      hepatic arteries in the setting of PAN is extremely rare. Patients are typically
      asymptomatic and, very rarely, spontaneous  rupture with life threatening
      haemorrhage could be the initial presentation of an undiagnosed PAN. Accurate
      diagnosis, effective haemostasis and prompt initiation of immunosuppressive
      treatment with the help of a multidisciplinary team will improve the clinical
      outcomes.

PMID- 22613290
TI  - SIADH following laparoscopic (totally extraperitoneal) inguinal hernia repair.
AB  - Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is recognised
      to occur after cardiac and traditional open abdominal surgery. However, SIADH
      after laparoscopic surgery is not well documented in the literature. We report a
      case of SIADH after laparoscopic (totally  extraperitoneal) inguinal hernia
      repair in an elderly man.

PMID- 22613291
TI  - A rare case of perforated caecum after acute pancreatitis.
AB  - Isolated caecal perforation following pancreatitis is a rare event. We report a
      case of severe non-necrotising pancreatitis complicated by caecal perforation
      that was managed successfully.

PMID- 22613292
TI  - Small bowel obstruction induced by spontaneous partial deflation of an
      intragastric balloon.
AB  - The intragastric balloon (IGB) has been used for decades as a temporary measure
      for weight reduction in the morbidly obese. Serious complications related to the
      device remain rare. We present the case of a 23-year-old Caucasian man who
      developed signs of bowel obstruction following spontaneous partial deflation of
      an air filled IGB with subsequent migration and impaction in the jejunum. We
      discuss the role of the IGB in the treatment of obesity, side effects and the
      serious complications that can occur.

PMID- 22613293
TI  - Prolonged survival after surgical management of metastases in malignant melanoma:
      three case reports.
AB  - The incidence of malignant melanoma is increasing and the management of
      metastatic disease remains a challenge to clinicians. We describe three cases
      where surgical management of metastases has resulted in prolonged survival.

PMID- 22613294
TI  - Subacute reaction to endoscopic mucosal resection mimicking perforation.
AB  - A 25-year-old woman underwent routine day-case endoscopic mucosal resection (EMR)
      of two ascending colonic polyps. Six hours later she re-presented with severe
      abdominal pain. On examination she was tachycardic with tenderness and peritonism
      in the right lower quadrant. Urgent abdominal  computed tomography (CT) did not
      reveal any signs of free intra-abdominal gas or fluid but did detect transmural
      thickening and oedema in the ascending colon and caecum. As there was no
      radiological evidence of perforation, the patient was managed conservatively and
      made a full recovery. The exact aetiology of this patient's symptoms is not
      known. She may have developed post-polypectomy electrocoagulation (a transmural
      diathermy injury), localised ischaemia of the colonic wall (secondary to the
      adrenaline used during EMR) or an allergic reaction to the dye used during EMR.
      As EMR is an increasingly used treatment modality in the management of colonic
      polyps, clinicians should have an awareness of the complications of treatment. We
      would advocate a low threshold for prompt CT investigation in any patient
      presenting with abdominal pain after EMR to detect any  evidence of free
      intraperitoneal air. Patients without signs of perforation may be managed
      conservatively, as in this case.

PMID- 22613295
TI  - Curating the world's peer-reviewed literature.
AB  - New technologies are transforming academic publishing, including surgical
      research. The author considers a variety of the new systems, platforms and search
      engines that are fuelling this information revolution, as well as the
      bibliometrics and citation analysis necessary for filtering  quality material for
      the increasingly inundated researcher.

PMID- 22613296
TI  - Update on drugs to treat diabetes.

PMID- 22613297
TI  - Pathophysiology and management aspects of adrenal angiomyolipomas.
AB  - Angiomyolipomas are benign mesenchymal tumours originating from the kidney and
      adrenals. They are rare tumours that can be sporadic and isolated or occur as a
      part of tuberous sclerosis. These tumours have a high content in the cells, which
      is pathognomonic for diagnosis using ultrasonography,  computed tomography and
      magnetic resonance imaging. Atypical angiomyolipomas occur with excessive smooth
      muscle cells and less adipose tissue, and are sensitive to immunohistochemistry
      studies. Most of these lesions are detected incidentally but some can cause back
      and abdominal pains if large  in size. Larger lesions are also vulnerable to
      spontaneous or traumatic rupture, causing large retropertitoneal bleeds. Surgery
      should be considered as the definitive management for larger lesions to avoid
      associated complications. There have been no reports of any malignant change
      being reported  in any of the lesions but a long follow-up period is still
      required, given the unknown clinical progression of these rare tumours.

PMID- 22613298
TI  - Effectiveness of a gentamicin impregnated collagen sponge on reducing sternal
      wound infections following cardiac surgery: a meta-analysis of randomised
      controlled trials.
AB  - INTRODUCTION: Gentamicin impregnated collagen sponges are licensed for use after
      cardiac surgery in over 50 countries but their effectiveness at preventing
      sternal wound infections (SWIs) remains uncertain. The aim of this meta-analysis
      was to assess the current evidence for effectiveness of such sponges at
      preventing SWIs in patients after cardiac surgery. METHODS: A systematic search
      of the literature was undertaken and meta-analyses were performed on the results
      of the identified, eligible studies. Using random effects models, odds ratios
      (OR) and corresponding 95% confidence intervals (CI) were calculated for all SWIs
      and deep SWIs for: a) all participants, and b) participants deemed as high risk.
      RESULTS: Three unique randomised controlled trials (published between 2005 and
      2010) involving 3,994 participants met the inclusion criteria. There was
      insufficient evidence of a significant difference between intervention and
      control groups for all SWIs (all participants: OR: 0.66, 95% CI: 0.39-1.14; high
      risk participants: OR: 0.60, 95% CI: 0.24-1.52). There was insufficient evidence
      of a significant benefit of the sponge in deep SWIs across all participants (OR:
      0.72, 95% CI: 0.47-1.10) but some evidence of benefit in terms of reducing the
      incidence of deep SWIs in high risk participants (OR: 0.62, 95% CI: 0.39-0.98).
      CONCLUSIONS: There is insufficient evidence of the effectiveness (or otherwise)
      of gentamicin impregnated sponges in preventing SWIs following cardiac surgery.
      However, some evidence does exist that such sponges can reduce the incidence of
      deep infections in high risk patients.

PMID- 22613299
TI  - Case-based review: conservative management of appendicitis--are we delaying the
      inevitable?
AB  - Acute appendicitis is a common surgical presentation for which surgical
      intervention, an appendicectomy, has remained a largely unchallenged primary
      treatment modality. Traditionally, it has been felt that the pathophysiological
      progressive nature of appendicitis ultimately leads to  perforation. A number of
      recent studies, however, suggest that the process of appendiceal inflammation may
      follow a more remitting nature with evidence indicating spontaneous resolution.
      It is hypothesised that the treatment of uncomplicated appendicitis may therefore
      be amenable to conservative  management with antibiotics. This article aims to
      highlight some of the issues and challenges relating to the conservative
      management of acute appendicitis and further demonstrates potential diagnostic
      and treatment difficulties involved in managing the more unfamiliar condition of
      recurrent  appendicitis.

PMID- 22613300
TI  - The STAR score: a method for auditing clinical records.
AB  - INTRODUCTION: Adequate medical note keeping is critical in delivering high
      quality healthcare. However, there are few robust tools available for the
      auditing of notes. The aim of this paper was to describe the design, validation
      and implementation of a novel scoring tool to objectively assess surgical notes.
      METHODS: An initial 'path finding' study was performed to evaluate the quality of
      note keeping using the CRABEL scoring tool. The findings prompted the development
      of the Surgical Tool for Auditing Records (STAR) as an alternative. STAR was
      validated using inter-rater reliability analysis. An audit cycle of surgical
      notes using STAR was performed. The results were analysed and a structured form
      for the completion of surgical notes was introduced to see if the quality
      improved in the next audit cycle using STAR. An education exercise was conducted
      and all participants said the exercise would change their practice, with 25%
      implementing major changes. RESULTS: Statistical analysis of STAR showed that it
      is reliable (Cronbach's alpha = 0.959). On completing the audit cycle, there was
      an overall increase in the STAR score from 83.344% to 97.675% (p < 0.001) with
      significant improvements in the documentation of the initial clerking from 59.0%
      to 96.5% (p < 0.001) and subsequent entries from 78.4% to 96.1% (p < 0.001).
      CONCLUSIONS: The authors believe in the value of STAR as an effective, reliable
      and reproducible tool. Coupled with the application of structured forms to note
      keeping, it can significantly improve the quality of surgical documentation and
      can be implemented universally.

PMID- 22613301
TI  - Changing incidence and management of penetrating neck injuries in the South East
      London trauma centre.
AB  - INTRODUCTION: A total of 17 cases of penetrating neck injury were managed by the
      otolaryngology team at King's College Hospital over a 3-year period in the 1980s.
      In April 2010 King's College Hospital became the major trauma centre for South
      East London. This prospective cohort study  compares the incidence, changing
      demographic features and treatment outcomes of penetrating neck trauma in South
      East London over the previous 23 years. METHODS: Data were collected over a 12
      month period (April 2010 to March 2011) and a selective management protocol was
      introduced to  standardise initial investigations and further treatment. RESULTS:
      The past 23 years have seen a 550% increase in the incidence of penetrating neck
      injuries in South East London, with a marked increase in gun crime. Only 38% of
      cases underwent negative neck exploration in 2011 compared  with 65% in 1987.
      Selective conservative management based on the absence of haemodynamic
      instability or radiological findings reduces length of hospital stay, lightens
      surgical workload and cuts costs without affecting morbidity or mortality.
      CONCLUSIONS: The increased incidence of penetrating  neck injury is a reflection
      of more interpersonal violence rather than a consequence of the larger South East
      London trauma centre catchment area. Tackling this problem requires focus on
      wider issues of community prevention. Sharing of data between the four London
      trauma centres and the police  is needed to help prevent interpersonal violence
      and develop a universal treatment algorithm for other institutions to follow.

PMID- 22613302
TI  - Gastric schwannoma: a benign tumour often mistaken clinically, radiologically and
      histopathologically for a gastrointestinal stromal tumour--a case series.
AB  - INTRODUCTION: Gastric schwannomas are rare mesenchymal tumours that arise from
      the nerve plexus of the gut wall. They present with non-specific symptoms and are
      often detected incidentally. Pre-operative investigation is not pathognomonic and
      many are therefore diagnosed as gastrointestinal stromal tumours (GISTs).
      Operative resection is usually curative as they are almost always benign,
      underpinning the importance of differentiating them from GISTs. METHODS: Three
      cases of gastric schwannomas were identified over a seven-year period. The
      clinical details and management were reviewed retrospectively. RESULTS: There
      were two women and one man with a mean age of 62 years (range: 51-69 years). Two
      patients presented with bleeding and one with abdominal pain. The mean tumour
      size was 5.2 cm (range: 2-10 cm) and the tumours were resected completely
      following total or wedge gastrectomies. Histology in all cases showed spindle
      cells with a cuff of lymphoid tissue. Immunohistochemistry confirmed positive
      S100 staining and negative CD117 and DOG-1 staining in all cases. CONCLUSIONS: We
      report our experience with these unusual primary stromal tumours of the gut and
      their presentations, pre-operative investigations, operative findings and
      pathological findings are discussed. Operative resection in all cases has been
      considered curative, which is supported by previous series confirming the
      excellent prognosis of gastric schwannomas.

PMID- 22613304
TI  - Caliper measurement to improve clinical assessment of palpable neck lumps.
AB  - INTRODUCTION: One-stop neck lump clinics with ultrasonography and cytopathology
      support are an expensive and finite resource. Consequently, many neck lump
      patients are assessed in general ear, nose and throat or head and neck clinics.
      Optimal clinical assessment of neck lump size is important to guide
      investigation, monitor change and provisionally stage nodal disease. The aims of
      this study were to investigate whether caliper measurement is more accurate than
      clinical palpation in assessing neck lump size and whether caliper measurement of
      neck lump size correlates closely with accurate ultrasonography measurement.
      METHODS: A prospective study was carried out involving 50 patients with
      clinically palpable neck lumps presenting to the one-stop neck lump clinic. Long
      and short axis neck lump dimensions were estimated first by clinical palpation
      and second by caliper measurement. Estimations were compared with accurate
      ultrasonography measurement. RESULTS: The mean combined long and short axis
      measurement deviation from accurate ultrasonography measurement was smaller for
      caliper measurement (7.80 mm) than for clinical palpation (12.38 mm) (p <0.01).
      There was no significant difference observed between combined axis
      ultrasonography and combined axis caliper measurement of neck lumps (p = 0.462).
      CONCLUSIONS: Caliper measurement is more accurate than clinical palpation in
      estimating the size of clinically palpable neck lumps. The use of calipers to
      measure the skin surface dimensions of palpable neck lumps is statistically
      comparable to accurate ultrasonography measurement.

PMID- 22613303
TI  - An observational study into the management of arteriomegaly: a call for a revised
      classification system.
AB  - INTRODUCTION: Arteriomegaly is the diffuse ectasia of arteries with or without
      aneurysmal disease. Patients with arteriomegaly have a higher incidence of
      morbidity including limb loss compared to patients with other arteriopathies. The
      aim of this observational study was to review the management of these patients in
      our institution. METHODS: Radiologists and surgeons prospectively reviewed
      aortofemoral angiography. Patients with arteriomegaly were identified. Data
      relating to demographics, mode of presentation, risk factors, type of
      arteriomegaly, management and progression of disease were analysed. RESULTS:
      Arteriomegaly was identified in 1.3% of patients (n = 69) undergoing lower limb
      angiography in the study period. Of these, the majority (n = 67) were men. The
      mean age was 74 years (range: 60-89 years) and 76% were smokers. Co-morbidities
      included coronary artery disease (55%), diabetes mellitus (20%), hypertension
      (45%) and cerebrovascular events (6%). Forty-nine patients presented with
      critical limb ischaemia and eighteen patients were seen electively in the
      outpatients department with symptoms of intermittent claudication. Data were
      incomplete for two male patients and were therefore not included. At
      presentation, 22 patients were classified as Hollier type I, 5 were type II and 9
      were type III. Thirty-one patients had arteriomegalic vessels but no aneurysmal
      disease. After a median follow-up duration of 76 months (range: 6-146 months), 34
      patients progressed to type I, 2 to type II and 18 to type III. Thirteen remained
      without aneurysmal disease. Twenty-nine patients required angioplasty and twenty
      eight required bypass surgery during this time. In total, 102 procedures were
      required for complicated disease. The limb salvage rate was 92%. Although 8
      patients in our series died, the remaining 59 are under regular follow up.
      CONCLUSIONS: This study illustrates the progressive nature of arteriomegaly.
      Results of the management of these patients in our institution are similar to
      those in the literature. We suggest an additional fourth category to Hollier's
      classification that describes arteriomegalic disease without aneurysmal
      degeneration as this, too, deserves special management. Regular follow-up visits
      and early intervention for patients with arteriomegaly is advocated to reduce the
      high incidence of morbidity.

PMID- 22613305
TI  - Early symptoms of bone and soft tissue sarcomas: could they be diagnosed earlier?
AB  - INTRODUCTION: Delays in diagnosis are common for patients with bone and soft
      tissue sarcoma (STS) despite guidance produced by the National Institute for
      Health and Clinical Excellence. This study set out to identify early symptoms
      experienced by patients and reasons for delays in making  a definitive diagnosis.
      METHODS: Retrospective interviews were carried out with 107 patients (66 with an
      STS and 41 with a bone sarcoma) presenting to a specialist centre. Symptoms were
      determined prior to definitive diagnosis and the occurrence of patient and doctor
      delays in reaching  specialist care. RESULTS: The median patient delay was 1
      month while the median doctor delay was 3.2 months from first symptoms to
      diagnosis for all sarcomas. Forty-nine patients with STS (74%) presented
      initially to their general practitioner with at least one guideline feature to
      prompt  urgent referral. Only 2 patients (4%), however, were referred directly to
      a sarcoma unit, with 21 (43%) referred to secondary care for investigation.
      Patients with a lump increasing in size exhibited longer patient delays while
      doctor delay was shorter for deep lumps. Thirty-six patients with  a bone sarcoma
      (88%) presented initially with symptoms to prompt further investigation.
      Nevertheless, significant delays (3.9 months) were seen in reaching specialist
      care. Only 4 patients (10%) were referred directly to a sarcoma unit at first
      presentation, with 21 (54%) referred for further  investigation elsewhere.
      CONCLUSIONS: It is evident that awareness and referral of sarcomas remain poor.
      We suggest specific amendments to current guidelines and clearer referral
      pathways for patients. Furthermore, the need for robust education strategies is
      indicated, predominantly among  healthcare professionals.

PMID- 22613306
TI  - Optimising fast track care for proximal femoral fracture patients using modified
      early warning score.
AB  - INTRODUCTION: The care for patients with a proximal femoral fracture has been
      dramatically overhauled with the introduction of 'fast track' protocols and the
      British Orthopaedic Association guidance in 2007. Fast track pathways focus on
      streamlining patient flow through the emergency department where the guidance
      addresses standards of care. We prospectively examined the impact these protocols
      have on patient care and propose an alternative 'streamed care' pathway to
      provide improved medical care within existing resource constraints. METHODS: Data
      surrounding the treatment of 156 consecutive patients managed at 4 centres were
      collated prospectively. Management of patients with a traditional fast track
      protocol allowed 17% of patients to leave the emergency department with
      undiagnosed serious medical pathology and 32% with suboptimal fluid
      resuscitation. A streamed care pathway based on the modified early warning score
      was developed and employed for 48 further patients as an alternative to the
      traditional fast track system. RESULTS: The streamed care pathway improved
      initial care significantly by treating patients according to their physiological
      parameters on admission. Targeted medical reviews on admission instead of the
      following day reduced the rates of undiagnosed medical pathology to 2% (p =
      0.0068) and inadequate fluid resuscitation to 11% (p < 0.0001). CONCLUSIONS:
      Implementation of a streamed care pathway can allow protocol driven improvement
      to initial care for patients with a proximal femoral fracture and results in
      improved access to initial specialist medical care.

PMID- 22613307
TI  - Seldinger method for intraoperative cholangiography: a practical approach.

PMID- 22613308
TI  - The genitofemoral nerve block: a method for hemiscrotal anaesthesia at the
      bedside.

PMID- 22613309
TI  - 'Scarless' removal of forehead lipomas.

PMID- 22613310
TI  - Twisted loop mattress suture.

PMID- 22613311
TI  - A half blooded knot for wound closure.

PMID- 22613312
TI  - A novel and easily reproducible method for reestablishing pneumoperitoneum during
      laparoscopic colorectal resectional surgery.

PMID- 22613313
TI  - A simple minimally invasive technique of removing lumbar disc debris following
      discectomy.

PMID- 22613314
TI  - Injecting patent blue dye V for sentinel lymph node biopsy without skin staining.

PMID- 22613315
TI  - How to reduce radiation exposure during hand surgery: use of a kidney dish to
      protect the surgeon's hands.

PMID- 22613316
TI  - Tongue and groove (v-shaped) osteotomy in treatment of non-union of long bones--a
      novel surgical technique.

PMID- 22613317
TI  - Purse string loop assistance for intracorporeal stapled anastomosis during
      laparoscopic anterior resection.

PMID- 22613318
TI  - A novel intra-operative technique to achieve accurate leg length and femoral
      offset during total hip replacement.

PMID- 22613319
TI  - Pin site cover: a simpleton's approach.

PMID- 22613321
TI  - A single institution experience with skin sparing mastectomy and immediate breast
      reconstruction.

PMID- 22613322
TI  - Management of boys with abnormal appearance of meatus at circumcision for
      balanitis xerotica obliterans.

PMID- 22613323
TI  - Increased use of pre-operative imaging and laparoscopy has no impact on clinical
      outcomes in patients undergoing appendicectomy.

PMID- 22613324
TI  - Clinical outcome of laparoscopic and open colectomy for right colonic carcinoma.

PMID- 22613325
TI  - Improving the success of nipple reconstruction.

PMID- 22613326
TI  - The impact of surgeon-based ultrasonography for parathyroid disease on a British
      endocrine surgical practice.

PMID- 22613327
TI  - Entonox(r) inhalation to reduce pain in common diagnostic and therapeutic
      outpatient urological procedures: a review of the evidence.

PMID- 22613329
TI  - [Interleukin 23 promotes lung adenocarcinoma a549 cell migration and invasion].
AB  - BACKGROUND AND OBJECTIVE: Interleukin 23 (IL-23) is a pro-inflammatory cytokine
      that plays an important role in inflammatory disease and tumor microenvironment.
      The IL-23 receptor is expressed in colon, lung, and oral carcinomas. We performed
      this study to investigate whether IL-23 promotes directly carcinoma cell
      migration and invasion as well as further explore its mechanism. METHODS: The
      migration and invasion of human lung adenocarcinoma A549 cells induced by IL-23
      were detected by a scratch test and Transwell experiment. MMP-9 expression of the
      mRNA and protein levels of A549 cells cultured with and without IL-23 was
      respectively detected by Real-time PCR and ELISA. The effect of IL-23 on A549
      cells was further verified using anti-IL-23p19 neutralization antibody (Ab IL
      23p19) to eliminate IL-23. RESULTS: IL-23 remarkably promoted A549 cell migration
      and invasion. MMP-9 expression in A549 cells was upregulated by IL-23
      stimulation. In addition, the effect of IL-23 on the migration and invasion of
      A549, as well as the MMP-9 expression in A549 cells induced by IL-23, was
      eliminated by Ab IL-23p19. CONCLUSION: IL-23 promotes the migration and invasion
      of A549 cells by inducing MMP-9 expression.

PMID- 22613330
TI  - [Construction of A eukaryotic expression vector carrying the iNOS gene and its
      effect on A549 lung cancer cells].
AB  - BACKGROUND AND OBJECTIVE: The iNOS gene is associated with NO-mediated antitumor
      effects. The aims of this study are to construct a eukaryotic expression plasmid
      that carries the iNOS gene and to detect the expression levels and antitumor
      effects of the iNOS gene on A549 lung cancer cells. METHODS: A DNA fragment of
      the human iNOS coding sequence was amplified using reverse transcription
      polymerase chain reaction (RT-PCR). The DNA fragment was subsequently cloned into
      the multiple cloning sites of the eukaryotic expression vector pVAX. The
      recombinant plasmid was confirmed using restriction enzyme treatment, PCR, and
      sequencing and was then transfected into A549 lung cancer cells. The expression
      of the iNOS gene in the A549 lung cancer cells after transfection was verified by
      RT-PCR and Western blot analysis. The effects of iNOS on cell apoptosis,
      proliferation, and migration were identified by staining with Hoechst 3235, an
      MTT assay, and a scratch assay, respectively. RESULTS: The results of the
      restriction enzyme digestion, PCR, and sequencing verified the successful
      construction of the eukaryotic expression plasmid pVAX-iNOS. The iNOS gene
      expression level was increased in the transfected A549 cells. Further experiments
      also showed increased cell apoptosis among the A549 lung cancer cells transfected
      with pVAX-iNOS. Meanwhile, the proliferation and migration of A549 cells were
      significantly inhibited by the enhanced iNOS gene expression. CONCLUSION: The
      recombinant eukaryotic expression vector pVAX-iNOS was successfully constructed
      and transfected into A549 cells. The enhanced iNOS gene expression significantly
      promoted cell apoptosis, whereas the proliferation and migration of A549 cells
      were inhibited. These findings contribute to the development of novel and
      effective gene therapies for lung cancer.

PMID- 22613331
TI  - [Establishment and characterization of a human lung adenocarcinoma cell line, Ch
      Huang-1].
AB  - BACKGROUND AND OBJECTIVE: Lung cancer is a major worldwide health problem. The
      aim of this study is to establish a novel Chinese human lung adenocarcinoma cell
      line and examine its biological characteristics. METHODS: Lung adenocarcinoma
      specimens were freshly resected during surgery. The tissues were incubated in
      vitro and the cell line was named Ch-Huang-1. The biological characteristics of
      the cells were investigated by light microscopy, chromosome analysis, and
      transplantation experiment. RESULTS: Light microscopy revealed that cells from
      the primary tumor, Ch-Huang-1 cell line, and transplanted tumor possessed the
      characteristics of a malignant glandular epithelial tumor. The cell growth curve,
      doubling time, and mitotic index were also observed in vitro. Nuclear chromosome
      analysis revealed that the tumor was a subtriploid with a mode of 35-44 per cell.
      Tumor nodes were observed under the skin of nude mice by heterogenic
      transplantation. CONCLUSION: The characteristics of the established cell line
      suggest that it is a newly established human adenocarcinoma cell line.

PMID- 22613332
TI  - [Effects of tea polyphenols on the expression of NF-kappaB, COX-2 and survivin in
      Lewis lung carcinoma xenografts in C57BL/6 mice].
AB  - BACKGROUND AND OBJECTIVE: Lung cancer is the leading cause of cancer-related
      deaths worldwide. The anti-angiogenic effect of tea polyphenols (TPs) on lung
      carcinoma was confirmed in our previous study. The effect of TPs on the
      expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF
      kappaB), cyclooxygenase-2 (COX-2), and Survivin in Lewis lung cancer xenograft in
      mice was observed to explore the anti-angiogenic mechanism of TPs. METHODS: Lewis
      lung carcinoma was successfully implanted in 32 C57BL/6 mice, which were then
      randomly divided into the model control group, the Thalidomide group, the TPs
      group and the TPs combined with Thalidomide group. The tumor inhibition rates in
      these groups were determined, whereas the expressions of NF-kappaB, COX-2 and
      Survivin were detected using immunohistochemical techniques to investigate the
      molecular mechanism of the anti-tumor effect of TPs. RESULTS: (1) The tumor
      inhibition rates in the Thalidomide control group, the TPs group and the TPs plus
      Thalidomide group were 17.26%, 20.81%, 44.32% respectively. Compared with the
      model control group, the tumor inhibition rate was significantly higher in the
      TPs plus Thalidomide group (P<0.05); (2) Compared with the model control group,
      the expression of NF-kappaB was significantly decreased in the TPs group and the
      TPs plus Thalidomide group, and it was significantly downregulated in the latter
      (P<0.05); (3) The expression of COX-2 decreased in all treatment groups, and was
      significantly downregulated in the TPs plus Thalidomide group compared with the
      model control group (P<0.05); (4) Compared with the model control group, Survivin
      expression was significantly downregulated in all treatment groups (P<0.05), and
      was most obviously reduced in the TPs plus the Thalidomide group (P<0.01).
      CONCLUSION: TPs plus Thalidomide significantly inhibits Lewis lung cancer growth.
      TPs possibly downregulates the expression of NF-kappaB, COX-2 and Survivin in
      tumor tissue, thereby playing important roles in anti-angiogenesis.

PMID- 22613333
TI  - [Hypoxia upregulates the expression of annexin A1 in lung adenocarcinoma a549
      cells].
AB  - BACKGROUND AND OBJECTIVE: The growth of tumor often faced up with lackness of
      blood and oxygen, and it has been reported that Annexin A1 may be involved in
      tumor. The aim of this investigation is to explore the characteristics of
      expression of Annexin A1 in lung adenocarcinoma A549 cells after hypoxia.
      METHODS: A549 cells were exposured to either normoxia (21%O2) or hypoxia (1%O2)
      condition for 4 h, 12 h, 24 h. The expressions of Annexin A1 mRNA levels were
      measured by RT-PCR. The expressions of Annexin 1 protein were investigaged by
      Western blot. The relative content of reactive oxygen species (ROS) were assayed
      by special kit. The expressions of nuclear translocation of NF-kappaB was assayed
      by Western blot; After been treated with ROS scavenger NAC and PDTC, the levels
      of Annexin 1 protein of A549 cells were measured by Western blot. RESULTS:
      Compared with normoxia group, the Annexin A1 mRNA in hypoxia group increased
      after 4 h, and then decreased gradually; Moreover, Annexin 1 protein levels of
      A549 cells were also increased when treated with hypoxia. An increaing of ROS
      production in cells exprosed to hypoxia was detected. NAC and PDTC inhibited
      hypoxia-induced Annexin A1 increase. CONCLUSION: Hypoxia upregulates the
      expression of Annexin A1 in lung adenocarcinoma A549 cells, in which process ROS
      NF-kappaB may paticipate in.

PMID- 22613334
TI  - [Efficacy of gemcitabine and vinorelbine in first-line treatment with advanced
      non-small cell lung cancer: a multicentre retrospective study].
AB  - BACKGROUND AND OBJECTIVE: Chemotherapy has become the mainstay of first-line
      therapy. Non-platinum containing drugs are characterized by favorable toxicity
      profiles and is better tolerated than platinum-based regimens. The aim of this
      study is to detect the efficacy and toxicity of gemcitabine and vinorelbine (GN)
      in advanced non-small cell lung cancer (NSCLC) first-line treatment in China.
      METHODS: We retrospectively reviewed 67 NSCLC patients treated with this agent at
      five Hospital in China from Jan 2004 to Jun 2010. Survival analysis was evaluated
      by Kaplan-Meier method, multivariate analyses were performed to find prognostic
      markers using Cox proportional hazards model. RESULTS: A total of 67 patients
      were analyzed in this study. There were 52 patients with RRM1 negative and ERCC1
      positive. The objective response rate was 34.3%. The disease control rate was
      76.1%. The progression-free survival and median overall survival was 5.5 and 22.1
      months, respectively. On multivariate analysis, performance status score and
      whether further treatment were independent prognostic factor for overall
      survival. CONCLUSION: The GN agent is effective for the first line treatment in
      advanced non-small cell lung cacer. The toxicity is well tolerated.

PMID- 22613335
TI  - [Proteomics-based identification of proapoptotic caspase adapter protein as a
      novel serum marker of non-small cell lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Early diagnosis and treatment of lung cancer contribute
      to a patient's prolonged survival. Proteomics and tissue culture were used to
      screen potential serum markers of lung cancer. METHODS: The differential
      proteomic technique and matrix-assisted laser desorption/ionization-time of
      flight mass spectrometry were used to identify overexpressed proteins from
      cultured tumor tissues in a conditioned medium. Paired lung tissues in a
      conditioned medium were used as the control group. Overexpressed proapoptotic
      caspase adaptor protein (PACAP) was identified using Western blot and enzyme
      linked immunosorbent assay (ELISA). RESULTS: The expression of nineteen protein
      spots exhibited a twofold increase compared with that in the control group.
      Fourteen of which were identified, including the distinctly overexpressed PACAP.
      Western blot analysis revealed a high level of PACAP in the lung adenocarcinoma
      in both tissue culture media and patients' serum. Overexpressed PACAP was also
      detected in the serum of non-small cell lung cancer patients via ELISA compared
      with that in the serum of small cell lung cancer patients, benign lung tumor
      patients, and healthy individuals (P<0.05). CONCLUSION: PACAP is a potential
      serum marker of non-small cell lung cancer.

PMID- 22613336
TI  - [Effects of EGFR-TKIs on sequential pemetrexed?for advanced pulmonary
      adenocarcinoma].
AB  - BACKGROUND AND OBJECTIVE: Pemetrexed and epidermal growth factor receptor (EGFR)
      tyrosine kinase inhibitors (TKIs) were used in patients with EGFR mutation to
      determine their effects. This study analyzed the influence of EGFR-TKIs on
      pemetrexed by observing the clinical efficacy and toxicity of pemetrexed
      following responses to EGFR-TKIs. METHODS: Pulmonary adenocarcinoma patients were
      divided into EGFR-TKIs and no-EGFR-TKI groups according to the targeted therapy.
      All patients received pemetrexed (500 mg/m2) as second (or higher)-line
      treatment. The Response Evaluation Criteria in Solid Tumors (version 1.0) were
      used to evaluate the response to pemetrexed. Adverse events were classified based
      on version 4.0 of the National Cancer Institute Common Toxicity Criteria.
      RESULTS: There were 57 patients in the EGFR-TKIs group and 56 in the no-EGFR-TKIs
      group. The disease control rates (DCRs) were 77.2% and 67.9% (P=0.367). The
      progression free survival (PFS) periods were 5.95 and 3.55 months (P=0.535). The
      overall survival (OS) periods were 10.10 and 8.24 months (P=0.432). However,
      these values were not statistically significant. The common toxicities of
      pemetrexed were hematologic and gastrointestinal (grades I and II). Two patients
      in the EGFR-TKIs group discontinued pemetrexed because of severe toxicities,
      which were not observed in the no-EGFR-TKIs group. Both groups had one patient
      who reduced dosage because of myelosuppression (grade IV). There were five and
      nine patients in the EGFR-TKIs and no-EGFR-TKIs groups, respectively, who delayed
      therapy not because of severe toxicities but due to subjective factors.
      CONCLUSION: The DCRs, PFS periods, and OS periods of the patients administered
      with pemetrexed following EGFR-TKIs were better than those of the EGFR-TKIs
      group, but the differences were not statistically significant. Therefore,
      sequential pemetrexed administration caused negligible toxicities and can be used
      in adenocarcinoma therapy following responses to EGFR-TKIs.

PMID- 22613337
TI  - [Clinical observation of EGFR-TKI as a first-line therapy on advanced non-small
      cell lung cancer].
AB  - BACKGROUND AND OBJECTIVE: It has been proven that epidermal growth factor
      receptor-tyrosine kinase inhibitor (EGFR-TKI) significantly benefits advanced non
      small cell lung cancer (NSCLC) patients harboring EGFR mutations in progression
      free survival time with better tolerance. This study is undertaken to analyze
      efficacy and tolerance of advanced NSCLC patients harboring EGFR mutations taking
      EGFR-TKI as a first-line therapy. METHODS: Tumor samples from 54 patients with
      advanced NSCLC were examined for EGFR activating mutations (deletion mutation in
      exon 19 and the L858R point mutation in exon 21) by direct sequencing. The
      patients were first-line treated with oral administration of EGFR-TKI until
      disease progression. The efficacy and adverse events were observed, and survival
      was followed up. RESULTS: Among the patients, 61% (33 of 54) had EGFR exon 19
      deletion, and 39% (21 of 54) had EGFR L858R point mutation. All patients received
      first-line TKI therapy. The total response rate was 96%, median progression free
      survival (PFS) was 8.3 months and median survival was 19.5 months. The patients
      with EGFR exon 19 deletion had significantly longer median PFS (9 versus 7
      months, P=0.002) and longer median overall survival (OS)(25 versus 16 months,
      P=0.001) than patients with EGFR L858R point mutation. There is no significance
      in efficacy between gefitinib and erlotinib, and gefitinib is safer than
      erlotinib. The most common adverse events were rash and diarrhea. Two (4%) grade
      4 skin toxity effects, two (4%) grade 3 aminotransferase level elevations, and
      one (1) grade 3 stomatitis were observed. CONCLUSION: The first-line EGFR-TKI
      treatment in advanced NSCLC patients harboring EGFR mutations is efficient and
      safe, which is more efficient in patients with EGFR exon 19 deletion than those
      with EGFR L858R mutation.

PMID- 22613338
TI  - [Selected arterial infusion chemotherapy combined with target drugs for non-small
      cell lung cancer with multiple brain metastase].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study is to evaluate the efficacy of
      selected arterial infusion chemotherapy in treating non-small cell lung cancer
      (NSCLC) with multiple brain metastases and corresponding factors to influencing
      prognosis. METHODS: From September 2008 to October 2011, a total of 31 patients
      of NSCLC with multiple brain metastases (>=3) received selected incranial,
      bronchial and corresponding target arterial infusion chemotherapy combined with
      EGFR-TKIs. Interventional treatment was performed every four weeks, two-six
      cycles with synchronized or sequential targeted drugs (erlotinib, gefitinib or
      icotinib). Follow-up CT and MRI were regularly finished at interval of four weeks
      after two cycles of interventional treatment were finished or during taking
      targeted drugs in order to evaluate efficacy of the therapy. The procedure was
      stopped for the tumor disease was worse or the patient could not tolerate the
      toxity of drugs any longer. RESULTS: 31 patients was performed two to six cycles
      of interventional therapy, 3 cycles at average. Response assessment showed that 5
      (16.1%) patients got a complete response (CR), 7 (22.6%) had a partial response
      (PR), 11 (35.5%) had a stable disease (SD) and 8 (25.8%) had a progressive
      disease (PD). The objective response rate (ORR) was 38.7%, and the disease
      control rate was 74.2%. The median progression free survival (PFS) and overall
      survival (OS) were 13.1 months and 15.1 months. The 6-month survival rate, one
      year survival rate and two-year survival rate were 79%, 61.1%, and 31.1%,
      respectively. The patients' OS and PFS were influenced by smoking state, tumor
      pathology, extracranial metastases, period of targeted drug taking and
      performance status, not by sex, age, before therapy and the total of brain
      metastases. CONCLUSION: Selected arterial infusion chemotherapy with targeted
      drugs is one of the most effective and safe treatment to NSCLC with multiple
      brain metastases. Smoking status, tumor pathology, extracranial metastases,
      targeted drug taking and performance status are corresponding the patient's
      prognosis.

PMID- 22613339
TI  - [Progress of treatments in non-small cell lung cancer with brain metastases].
AB  - Brain metastases is one of the most common complications of non-small cell lung
      cancer, whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), surgery
      and chemotherapy are standard methods in the treatment of brain metastases. But
      the effect of those treatments are still sad. Comprehensive treatment can prolong
      the survival and improve the quality of life. Recently, the improvement of
      technology, targeted therapy, survival time and the quality of life are in
      increasingly concerned. The paper make a summary of current situation and
      progress for comprehensive therapy of brain metastases.

PMID- 22613340
TI  - [A case report of anterior-mediastinal bulky lesion].

PMID- 22613341
TI  - Health reform monitor--the impact of the financial crisis.

PMID- 22613342
TI  - Multidisciplinary care of patients receiving cardiac resynchronization therapy is
      associated with improved clinical outcomes.
AB  - AIMS: Although cardiac resynchronization therapy (CRT) reduces morbidity and
      mortality in patients with heart failure, a significant minority of patients do
      not respond adequately to this therapy. The objective of this study was to
      examine the impact of a 'multidisciplinary care' (MC) approach on the clinical
      outcome in CRT patients. METHODS AND RESULTS: The clinical outcome in patients
      prospectively receiving MC (n = 254) was compared with a control group of
      patients who received conventional care (CC, n = 173). The MC group was followed
      prospectively in an integrated clinic setting by a team of subspecialists from
      the heart failure, electrophysiology, and echocardiography service at 1-, 3-, and
      6-months post-implant. All patients had echocardiographic-guided optimization at
      their 1-month visit. The proportional hazards model (adjusting for all
      covariates) and Kaplan-Meier time to first event curves were compared between the
      two groups, over a 2-year follow-up. The long-term outcome was measured as a
      combined endpoint of heart failure hospitalization, cardiac transplantation, or
      all-cause mortality. The clinical characteristics between the MC and CC groups at
      baseline were comparable (age, 68 +/- 13 vs. 69 +/- 12; NYHA III, 90 vs. 82%;
      ischaemic cardiomyopathy 55 vs. 64%, P = NS, respectively). The event-free
      survival was significantly higher in the multidisciplinary vs. the CC group (P =
      0.0015). A significant reduction in clinical events was noted in the MC group vs.
      the CC group (hazard ratio: 0.62, 95% CI: 0.46-0.83, P = 0.001). CONCLUSION:
      Integrated MC may improve 2-year event-free survival in patients receiving
      cardiac resynchronization therapy. Prospective randomized studies are needed to
      validate our findings.

PMID- 22613343
TI  - Multiple heart injuries caused by fracture and migration of the inferior vena
      stent.

PMID- 22613344
TI  - Incremental value of global systolic dyssynchrony in determining the occurrence
      of functional mitral regurgitation in patients with left ventricular systolic
      dysfunction.
AB  - AIMS: The aim of this study was to assess the contribution of left ventricular
      (LV) systolic dyssynchrony to functional mitral regurgitation (MR). METHODS AND
      RESULTS: Patients (n = 136) with LV systolic dysfunction (ejection fraction <50%)
      and at least mild MR were prospectively recruited. The effective regurgitant
      orifice area (EROA) was assessed by the proximal isovelocity surface area method.
      Left ventricular global systolic dyssynchrony [the maximal difference in time to
      peak systolic velocity among the 12 LV segments (Ts-Dif)] and regional systolic
      dyssynchrony (the delay between the anterolateral and posteromedial papillary
      muscle attaching sites) were assessed by tissue Doppler imaging. Left ventricular
      global and regional remodelling, systolic function, indices of mitral valvular
      and annular deformation were also measured. The size of the EROA correlated with
      the degrees of mitral deformation, LV remodelling, systolic function, and
      systolic dyssynchrony. By multivariate logistic regression analysis, the mitral
      valve tenting area (OR = 1.020, P < 0.001) and the Ts-Dif (OR = 1.011, P = 0.034)
      were independent determinants of significant functional MR (defined by EROA >=20
      mm(2)). From the receiver-operating characteristic curve, the tenting area of 2.7
      cm(2) (sensitivity 83%, specificity 82%, AUC 0.86, P < 0.001) and the Ts-Dif of
      85 ms (sensitivity 66%, specificity 72%, AUC 0.74, P < 0.001) were associated
      with significant functional MR. The assessment of Ts-Dif showed an incremental
      value over the mitral valve tenting area for determining functional MR (chi(2) =
      53.92 vs.49.11, P = 0.028). CONCLUSION: This cross-sectional study showed that LV
      global, but not regional systolic dyssynchrony, is a determinant of significant
      functional MR in patients with LV systolic dysfunction, and is incremental to the
      tenting area that is otherwise the strongest factor for mitral valve deformation.

PMID- 22613346
TI  - Blockbuster interactions: are they bad for the patient?

PMID- 22613345
TI  - Abrogated transforming growth factor beta receptor II (TGFbetaRII) signalling in
      dendritic cells promotes immune reactivity of T cells resulting in enhanced
      atherosclerosis.
AB  - AIMS: The importance of transforming growth factor beta (TGFbeta) as an immune
      regulatory cytokine in atherosclerosis has been established. However, the role of
      TGFbeta signalling in dendritic cells (DCs) and in DC-mediated T cell
      proliferation and differentiation in atherosclerosis is unknown. METHODS AND
      RESULTS: Here, we investigated the effect of disrupted TGFbeta signalling in DCs
      on atherosclerosis by using mice carrying a transgene resulting in functional
      inactivation of TGFbeta receptor II (TGFbetaRII) signalling in CD11c(+) cells
      (Apoe(-/-)CD11cDNR). Apoe(-/-)CD11cDNR mice exhibited an over two-fold increase
      in the plaque area compared with Apoe(-/-) mice. Plaques of Apoe(-/-)CD11cDNR
      mice showed an increase in CD45(+) leucocyte content, and specifically in CD3(+),
      CD4(+) and CD8(+) cells, whereas macrophage content was not affected. In lymphoid
      organs, Apoe(-/-)CD11cDNR mice had equal amounts of CD11c(+) cells, and
      CD11c(+)CD8(+) and CD11c(+)CD8(-) subsets, but showed a subtle shift in the
      CD11c(+)CD8(-) population towards the more inflammatory CD11c(+)CD8(-)CD4(-) DC
      subset. In addition, the number of plasmacytoid-DCs decreased. Maturation markers
      such as MHCII, CD86 and CD40 on CD11c(hi) cells did not change, but the CD11cDNR
      DCs produced more TNFalpha and IL-12. CD11c(+) cells from CD11cDNR mice strongly
      induced T-cell proliferation and activation, resulting in increased amounts of
      effector T cells producing high amounts of Th1 (IFN-gamma), Th2 (IL-4, IL-10),
      Th17 (IL-17), and Treg (IL-10) cytokines. CONCLUSION: Here, we show that loss of
      TGFbetaRII signalling in CD11c(+) cells induces subtle changes in DC subsets,
      which provoke uncontrolled T cell activation and maturation. This results in
      increased atherosclerosis and an inflammatory plaque phenotype during
      hypercholesterolaemia.

PMID- 22613347
TI  - Dopamine depletion increases the power and coherence of high-voltage spindles in
      the globus pallidus and motor cortex of freely moving rats.
AB  - Studies on patients with Parkinson's disease and in animal models have observed
      enhanced synchronization of oscillations in several frequency bands within and
      between the cortical-basal ganglia (BG) structures. Recent research has also
      shown that synchronization of high-voltage spindles (HVSs) in the cortex,
      striatum and substantia nigra pars reticulate is increased by dopamine depletion.
      However, more evidence is needed to determine whether HVS activity in the whole
      cortex-BG network represents homologous alteration following dopamine depletion.
      As the globus pallidus (GP) is in a central position to propagate and synchronize
      oscillations in the cortical-BG circuits, we employed local-field potentials and
      electrocorticogram to simultaneously record oscillations in the GP and primary
      (M1) and secondary (M2) motor cortices on freely moving 6-hydroxydopamine (6
      OHDA) lesioned and control rats. Results showed that HVS episodes recorded from
      GP, and M2 and M1 cortex areas were more numerous and longer in 6-OHDA lesioned
      rats compared to controls. Relative power associated with HVS activity in the GP,
      and M2 and M1 cortices of 6-OHDA lesioned rats was significantly greater than
      that for control rats. Coherence values for HVS activity between the GP, and M2
      and M1 cortex areas were significantly increased by dopamine depletion. Time lag
      between the M1 cortex HVS and GP HVS was significantly shorter for dopamine
      depleted than normal rats. Findings indicate a crucial rule for dopamine in the
      regulation of HVS activity in the whole cortical-BG circuit, and suggest a close
      relationship between abnormally synchronized HVS oscillations in the cortex-BG
      network and Parkinson's disease.

PMID- 22613348
TI  - Hyperstimulation of macropinocytosis leads to lysosomal dysfunction during
      exposure to methamphetamine in SH-SY5Y cells.
AB  - Although various cytotoxic effects on neuronal cells caused by methamphetamine
      (METH) have been investigated, the cellular and molecular mechanisms of METH
      induced neurotoxicity remain to be elucidated. We previously reported that METH
      induced cytomorphological effects on retinoic acid (RA)-differentiated SH-SY5Y
      human neuroblastoma cells involved macropinocytosis, which is an actin-dependent
      endocytic pathway. We also noted that hyperstimulation of this process might play
      an important role in the cytotoxicity of METH in neuronal cells. In this study,
      we investigated the molecular mechanisms as well as subsequent outcomes of
      macropinocytosis during METH treatment. It was found that macropinosomes formed
      upon exposure to METH were colocalized with constitutively active GFP-Ras (G12V)
      and GFP-Rac1 (Q61L). Furthermore, both Ras inhibitor, farnesylthiosalicylic acid
      (FTS), and Rac1 inhibitor, EHT1864, significantly inhibited the formation of
      macropinosomes, suggesting the involvement of these molecules. The expressions of
      lysosome-associated membrane proteins (lamps) gradually increased by METH in a
      time-dependent manner. In contrast, the proteolytic activation of cathepsin L, a
      marker of lysosomal function, was markedly suppressed by METH. METH-induced
      dysfunction of lysosomal enzyme as well as cell death was significantly
      attenuated by nocodazole, a microtube interfering reagent that inhibits the
      transport of vesicles, including macropinosome, to lysosomes. Our results
      indicate that METH has cytotoxic effects, at least in part, by inhibiting normal
      lysosomal function through Ras- and Rac1-mediated macropinocytosis in RA
      differentiated SH-SY5Y cells.

PMID- 22613349
TI  - Cluster analysis for identifying sub-types of tinnitus: a positron emission
      tomography and voxel-based morphometry study.
AB  - Tinnitus is a heterogeneous disorder with respect to its etiology and phenotype.
      Thus, the identification of sub-types implicates high relevance for treatment
      recommendations. For this aim, we used cluster analysis of patients for which
      clinical data, positron-emission tomography (PET) data and voxel-based
      morphometry (VBM) data were available. 44 patients with chronic tinnitus were
      included in this analysis. On a phenotypical level, we used tinnitus distress,
      duration, and laterality for clustering. To correct PET and VBM data for age,
      gender, and hearing, we built up a design matrix including these variables as
      regressors and extracted the residuals. We applied Ward's clustering method and
      forced cluster analysis to divide the data into two groups for both imaging and
      phenotypical data. On a phenotypical level the clustered groups differed only in
      tinnitus laterality (uni- vs. bilateral tinnitus), but not in tinnitus duration,
      distress, age, gender, and hearing. For grey matter volume, groups differed
      mainly in frontal, cingulate, temporal, and thalamic areas. For glucose
      metabolism, groups differed in temporal and parietal areas. The correspondence of
      classification was near chance level for the interrelationship of all three data
      set clusters. Thus, we showed that clustering according to imaging data is
      feasible and might depict a new approach for identifying tinnitus sub-types.
      However, it remains an open question to what extent the phenotypical and imaging
      levels may be interrelated. This article is part of a Special Issue entitled:
      Tinnitus Neuroscience.

PMID- 22613350
TI  - Robust guaranteed cost control for singular Markovian jump systems with time
      varying delay.
AB  - This paper is concerned with the guaranteed cost control for continuous-time
      singular Markovian jump systems with time-varying delay. Without using the free
      weighting matrices method, a delay-range-dependent condition is derived in terms
      of strict linear matrix inequality (LMI), which guarantees that the singular
      system is regular, impulse free and mean-square exponentially stable with an
      H(infinity) performance. Based on this, the existence condition of the guaranteed
      cost state feedback controller is proposed. A numerical example is given to
      illustrate the effectiveness and less conservatism of the proposed design method.

PMID- 22613351
TI  - Physical strain and urgent need for ergonomic training among gynecologic
      oncologists who perform minimally invasive surgery.
AB  - OBJECTIVES: There is limited data regarding physical strain and minimally
      invasive gynecologic surgery (MIS). We sought to evaluate ergonomic strain among
      gynecologic oncologists. METHODS: An online survey was sent to all physician
      members of the Society of Gynecologic Oncology in North America in 2010. The
      survey contained 42 questions and data was analyzed using univariate and
      bivariate analyses with summary statistics, t-tests, and chi-squared test.
      RESULTS: There were 260 respondents (31.2%) to the survey. Case mix was 26%
      benign and 64% oncologic surgery. Over 52% of respondents had been in practice
      for greater than 11 years and 52% practice in an academic setting. Physical
      discomfort related to MIS was reported in 88% (216/244) of surgeons with 52%
      reporting persistent pain. Increased pain symptoms were associated with surgeon's
      height, glove size, age and female gender. Patient body mass index (BMI) was
      associated with pain symptoms in surgeons performing conventional laparoscopic
      surgery, but not robotic surgery. To decrease pain, surgeons changed positions
      (78%), limited the number of cases per day (14%), spread cases throughout the
      week (6%), or limited the total number of cases (3%). Only 29% had received
      treatment at any time for pain symptoms. Treatment included physical therapy
      (59%), medical management (28%), surgery (13%), and time off (1%). Only 16% of
      those with pain symptoms had received formal ergonomic training. CONCLUSION:
      Physical strain rates of 88% are far greater than previously reported. Such
      prevalent occupational strain presents a growing problem in the face of
      increasing demand for MIS.

PMID- 22613352
TI  - Dual-console robotic surgery compared to laparoscopic surgery with respect to
      surgical outcomes in a gynecologic oncology fellowship program.
AB  - OBJECTIVE: Minimally invasive surgical techniques decrease surgical morbidity and
      recovery time. Studies demonstrate similar surgical outcomes comparing robotic to
      laparoscopic surgery. These studies have not accounted for the incorporation of
      fellow education. With the dual-console da Vinci Si Surgical System(r), a two
      surgeon approach could be performed. We sought to compare surgical outcomes at a
      gynecologic oncology fellowship program of traditional laparoscopic to robotic
      surgeries using the dual-console system. METHODS: We identified patients who
      underwent laparoscopic or robotic surgery performed by a gynecologic oncologist
      from November 2009-November 2010. Robotic surgeries were conducted using the dual
      console, utilizing a two surgeon approach. Surgeries involved a staff physician
      with a gynecologic oncology fellow. Statistical analysis was performed using
      student t-test and chi-squared analysis. RESULTS: A total of 222 cases were
      identified. Cases were analyzed in groups: all cases identified, all cancer
      cases, and endometrial cancer cases only. When analyzing all cases, no
      statistical difference was noted in total operating room time (172 vs. 175 min;
      p=0.6), pelvic lymph nodes removed (10.1 vs. 9.6; p=0.69), para-aortic lymph
      nodes dissected (3.7 vs. 3.8; p=0.91), or length of stay (1.5 vs. 1.3 days;
      p=0.3). There was a significant difference in total surgical time (131 vs.110
      min; p<0.0001) and EBL (157 vs.94 ml; p<0.0001), favoring robotic surgery. When
      analyzing all cancer cases, the advantage in total surgical time for robotic
      surgery was lost. Complications were similar between cohorts. CONCLUSION:
      Incorporating fellow education into robotic surgery does not adversely affect
      outcomes when compared to traditional laparoscopic surgery.

PMID- 22613353
TI  - Video-assisted thoracic surgery (VATS) evaluation of intrathoracic disease in
      patients with FIGO III and IV stage ovarian cancer.
AB  - OBJECTIVES: The aim of this study was to assess the influence of video-assisted
      thoracic surgery (VATS) on our treatment decisions in FIGO III and IV ovarian
      cancer patients. METHODS: Patients with ovarian cancer and suspected supra
      diaphragmatic involvement (pleural effusions, pleural carcinomatosis, lung
      metastasis, or enlarged supra-diaphragmatic lymph nodes) at chest computer
      tomography (CT) scan underwent VATS with or without laparoscopy (LSC) to decide
      for primary cytoreduction or neoadjuvant chemotherapy. Operation time, VATS
      complications (intrapleural hematoma, secondary hemorrhage with intervention,
      pneumonia and empyema) and shift in the therapeutic strategy due to VATS were
      evaluated. RESULTS: 17 patients were included into this study (1 patient with
      FIGO stage IIIb, 1 with IIIc and 15 with stage IV). The median operation time for
      VATS only was 46.5 min (range: 20-50 min, n=3). Perioperatively, no complications
      occurred. After surgical staging, the tumor was confined to the abdomen in four
      patients in whom primary cytoreduction was attempted. All other 13 patients
      underwent neoadjuvant chemotherapy. VATS altered the therapeutic management in
      6/17 ovarian cancer patients (3 times upstaging, 3 times downstaging). Negative
      predictive values (NPV) for local and diffuse pleural carcinomatosis ranged
      between 0.5 and 0.71. CONCLUSION: In this case series, VATS in addition to LSC
      showed negligible morbidity related to surgery and a short operation time. We
      were able to improve the accuracy of the FIGO staging and assessed operability
      more reliably in these patients than through imaging techniques alone.

PMID- 22613354
TI  - Stressing caveolae new role in cell mechanics.
AB  - It has been almost 60 years since caveolae were first visualized by Eichi Yamada
      and George Palade. Nevertheless, these specialized invaginations of the plasma
      membrane remain without clear and recognized physiological function. The recent
      identification of new caveolar components and the ability to probe cell mechanics
      with sophisticated opticophysical devices have shed new light on this fascinating
      organelle. Early studies from the 1970s suggested that caveolae could participate
      in the regulation of membrane dynamics. Recent data have established caveolae as
      mechanosensors that respond immediately to mechanical stress by flattening into
      the plasma membrane. Here, we focus on the molecular consequences that result
      from the caveolar disassembly/reassembly cycle induced by membrane tension
      variations at the surface of the cell under physiological and pathological
      conditions.

PMID- 22613356
TI  - Clinical audit on diagnostic accuracy and management of respiratory failure in
      COPD.
AB  - BACKGROUND: The aim of the study was to evaluate the adequacy of diagnosis and
      management of respiratory failure (RF) in COPD. METHODS: Retrospective analysis
      of the hospital discharge forms of COPD patients hospitalized for RF from January
      2007 to June 2008. Using the clinical audit tool, the primary end point was the
      accuracy of RF diagnosis. The secondary end points were mortality, re
      hospitalization rate, length of hospital stay, accuracy of long-term oxygen
      therapy (LTOT) prescription, and agreement of the treatments with the Global
      Initiative for Chronic Obstructive Lung Disease (GOLD) 2008 guidelines.
      Statistical analysis used Pearson and Spearman correlation test and the Cohen
      kappa for degree of agreement. Differences in demographics and clinical
      parameters were analyzed with the chi-square test, t test, or the Fisher test, as
      appropriate. RESULTS: We studied 130 patients, 81 males (62%), mean +/- SD age
      76.6 +/- 9.1 years. Arterial blood gas analysis (ABG) was performed in 118
      patients (90.8%), and in 77 (81%) a P(aO(2)) < 60 mm Hg was found at admission.
      Of these, 42 cases (54.5%) had no diagnosis of RF, despite a P(aO(2)) < 60 mm Hg.
      In 18 (19%) P(aO(2)) was >= 60 mm Hg; of these, 6 cases (33.3%) received an
      incorrect RF diagnosis. At discharge 8.1% of patients did not receive a diagnosis
      of RF, despite a compatible ABG. The highest mortality was found in the medicine
      departments (14.7%). The re-hospitalization rate at 90 days was 19.5%. Adherence
      of the treatment to the GOLD guidelines during hospitalization was confirmed in
      75.8% of patients. In 41.1% of cases LTOT was prescribed at discharge; in 24 out
      of 27 cases P(aO(2)) values were < 55 mm Hg. CONCLUSIONS: Agreement between
      diagnosis of RF and ABG values was found to be insufficient in about half the
      cases. Among secondary end points, adherence of the treatment to guidelines and
      LTOT prescription were, however, found to be good. Data showed significant
      inaccuracies in the management of RF at our institution.

PMID- 22613357
TI  - Dexmedetomidine: therapeutic use for the termination of reentrant
      supraventricular tachycardia.
AB  - OBJECTIVES: The current drug of choice for reentrant supraventricular tachycardia
      (SVT) is adenosine followed by verapamil or diltiazem. Although limitations and
      significant adverse events have been encountered over the years, an alternative
      effective and safe agent has not been available. Dexmedetomidine has recently
      been shown to have potential antiarrhythmic effects, and here we describe our
      experience in the acute termination of reentrant SVT. DESIGN: Retrospective case
      series. SETTING: Quaternary University Children's Hospital, Cardiac Intensive
      Care Unit. PATIENTS: Patients who received dexmedetomidine for SVT in the past 5
      years. INTERVENTIONS: None. OUTCOME MEASURES: SVT episodes terminated with
      dexmedetomidine were compared with episodes terminated with adenosine. RESULTS:
      Fifteen patients, median age of 10 days (6-16), were given 27 doses of
      dexmedetomidine, mean dose 0.7 +/- 0.3 mcg/kg, for a total of 27 episodes of SVT.
      Successful termination occurred in 26 episodes (96%) at a median time of 30
      seconds (20-35). Duration of sinus pause was 0.6 +/- 0.2 seconds, there was one
      episode of hypotension and no bradycardia and sedation lasted for 34 +/- 8
      minutes. Five patients received 27 doses of adenosine, with an overall successful
      cardioversion in 17 patients (63%) (P= .0017). Transient bradycardia and
      hypotension was seen in three patients (11%), agitation in 16 patients (59%), and
      broncospasm in one patient. Median sinus pause was 2.5 seconds (2-9) (P < .001).
      CONCLUSIONS: Dexmedetomidine appears to have novel antiarrhythmic properties for
      the acute termination of reentrant SVT. Although adenosine is very effective,
      dexmedetomidine may prove to possess a more favorable therapeutic profile with
      increased effectiveness and fewer side effects.

PMID- 22613355
TI  - Altered cofactor binding affects stability and activity of human UDP-galactose 4'
      epimerase: implications for type III galactosemia.
AB  - Deficiency of UDP-galactose 4'-epimerase is implicated in type III galactosemia.
      Two variants, p.K161N-hGALE and p.D175N-hGALE, have been previously found in
      combination with other alleles in patients with a mild form of the disease. Both
      variants were studied in vivo and in vitro and showed different levels of
      impairment. p.K161N-hGALE was severely impaired with substantially reduced
      enzymatic activity, increased thermal stability, reduced cofactor binding and no
      ability to rescue the galactose-sensitivity of gal10-null yeast. Interestingly
      p.K161N-hGALE showed less impairment of activity with UDP-N-acetylgalactosamine
      in comparison to UDP-galactose. Differential scanning fluorimetry revealed that
      p.K161N-hGALE was more stable than the wild-type protein and only changed
      stability in the presence of UDP-N-acetylglucosamine and NAD(+). p.D175N-hGALE
      essentially rescued the galactose-sensitivity of gal10-null yeast, was less
      stable than the wild-type protein but showed increased stability in the presence
      of substrates and cofactor. We postulate that p.K161N-hGALE causes its effects by
      abolishing an important interaction between the protein and the cofactor, whereas
      p.D175N-hGALE is predicted to remove a stabilizing salt bridge between the ends
      of two alpha-helices that contain residues that interact with NAD(+). These
      results suggest that the cofactor binding is dynamic and that its loss results in
      significant structural changes that may be important in disease causation.

PMID- 22613358
TI  - Ocular melanoma in a patient successfully treated for diffuse malignant
      peritoneal mesothelioma: a case report.
AB  - BACKGROUND: Diffuse malignant peritoneal mesothelioma and ocular melanoma are
      both rare tumors. To the best of our knowledge there is only one previous report
      of three cases in a family with known susceptibility to malignancies associating
      diffuse malignant peritoneal mesothelioma and ocular melanoma, with no sporadic
      cases previously reported. CASE PRESENTATION: We describe the case of a 59-year
      old man with a history of diffuse malignant peritoneal mesothelioma, who
      presented with ocular melanoma 41 months after cytoreductive surgery and
      hyperthermic intraperitoneal chemotherapy. We also briefly review the literature.
      CONCLUSIONS: Diffuse malignant peritoneal mesothelioma is an uncommon but
      aggressive disease. As diffuse malignant peritoneal mesothelioma
      characteristically remains confined to the abdominal cavity, any new extra
      abdominal symptom should eventually raise suspicion of another primary tumor. Few
      cases of diffuse malignant peritoneal mesothelioma associated with other primary
      tumors have been reported. As ocular melanoma is also infrequent, we suspect a
      genetic predisposition to these tumors. There is emerging evidence supporting the
      role of BAP1 mutations in the pathogenesis of these two neoplasias.

PMID- 22613361
TI  - What's on the horizon: defining physiatry through rehabilitation methodology.

PMID- 22613359
TI  - CLASPs function redundantly to regulate astral microtubules in the C. elegans
      embryo.
AB  - Microtubule dynamics are thought to play an important role in regulating
      microtubule interactions with cortical force generating motor proteins that
      position the spindle during asymmetric cell division. CLASPs are microtubule
      associated proteins that have a conserved role in regulating microtubule dynamics
      in diverse cell types. Caenorhabditis elegans has three CLASP homologs in its
      genome. CLS-2 is known to localize to kinetochores and is needed for chromosome
      segregation at meiosis and mitosis; however CLS-1 and CLS-3 have not been
      reported to have any role in embryonic development. Here, we show that depletion
      of CLS-2 in combination with either CLS-1 or CLS-3 results in defects in nuclear
      rotation, maintenance of spindle length, and spindle displacement in the one-cell
      embryo. Polarity is normal in these embryos, but reduced numbers of astral
      microtubules reach all regions of the cortex at the time of spindle positioning.
      Analysis of the microtubule plus-end tracker EB1 also revealed a reduced number
      of growing microtubules reaching the cortex in CLASP depleted embryos, but the
      polymerization rate of astral microtubules was not slower than in wild type.
      These results indicate that C. elegans CLASPs act partially redundantly to
      regulate astral microtubules and position the spindle during asymmetric cell
      division. Further, we show that these spindle pole-positioning roles are
      independent of the CLS-2 binding proteins HCP-1 and HCP-2.

PMID- 22613363
TI  - USBJI Musculoskeletal Summit introduction to summary and recommendations.

PMID- 22613362
TI  - Management metrics: meaning and applications.

PMID- 22613364
TI  - The value in musculoskeletal care: summary and recommendations.

PMID- 22613366
TI  - The rehabilitation of Anton syndrome.

PMID- 22613365
TI  - Neuroleptic malignant syndrome associated with the use of carbidopa/levodopa for
      dystonia in persons with cerebral palsy.

PMID- 22613367
TI  - Potential carcass enrichment of the University of Tennessee Anthropology Research
      Facility: a baseline survey of edaphic features.
AB  - The University of Tennessee Anthropology Research Facility (ARF) is known for its
      unique contribution to forensic science as a site of human decomposition
      research. Studies conducted at ARF are integral in our understanding of the
      processes of human decomposition. As such, the authors are interested in the long
      term effects of continuous human decomposition on the soil environment. Soil
      samples collected from within and outside the ARF were evaluated for moisture
      content, pH, organic content, total carbon and nitrogen content, and biomass by
      lipid-bound phosphorus, and total extracted DNA. Analyses revealed no significant
      differences (p<0.05) among the sampled areas within the facility, and yet
      demonstrated a possible trend toward increased levels of total N, Lipid-P, and
      water, suggesting an influx of high-quality nutrients into the ARF soil.
      Furthermore, elevated pH readings, presumably resulting from ammonification of
      the soil, were observed in areas of high decomposition. The negative control
      samples proved significantly different from nearly all samples collected within
      the facility, the exceptions being total carbon content and extractable DNA.
      These findings indicate that while landscape samples inside may be similar to
      themselves, they are dissimilar to those taken in a similar temperate forest
      biome with no recorded history of human decomposition.

PMID- 22613368
TI  - Set-shifting in adults with ADHD.
AB  - Difficulties related to inhibition and set-shifting have been suggested as
      possible endophenotypes of Attention Deficit Hyperactivity Disorder (ADHD).
      However, such difficulties have not been consistently found in studies using
      standard neuropsychological tests. This has been partly explained by the
      complexity of these tests and the need to include contrast measures which control
      for more basic functions. The purpose of the present study was to examine whether
      difficulties related to inhibition and set-shifting in adult ADHD patients could
      be revealed by the Color Word Interference Test (CWIT) from the Delis Kaplan
      Executive Function System (D-KEFS). A clinically recruited group of adults with
      ADHD (n = 60) obtained significantly lower scores than population derived
      controls (n = 60) on both primary summary (p < .001) and contrast measures (p =
      .004) of set-shifting. The differences between the groups remained statistically
      significant after controlling for intellectual function and working memory (p =
      .003). However, no significant differences between the groups were observed on
      any measure of inhibition. The study indicates that adults with ADHD have
      specific difficulties with set-shifting as measured by the CWIT, difficulties
      that probably also reflect problems related to executive function in their daily
      life.

PMID- 22613369
TI  - Boron neutron capture therapy (BNCT) in Finland: technological and physical
      prospects after 20 years of experiences.
AB  - Boron Neutron Capture Therapy (BNCT) is a binary radiotherapy method developed to
      treat patients with certain malignant tumours. To date, over 300 treatments have
      been carried out at the Finnish BNCT facility in various on-going and past
      clinical trials. In this technical review, we discuss our research work in the
      field of medical physics to form the groundwork for the Finnish BNCT patient
      treatments, as well as the possibilities to further develop and optimize the
      method in the future. Accordingly, the following aspects are described: neutron
      sources, beam dosimetry, treatment planning, boron imaging and determination, and
      finally the possibilities to detect the efficacy and effects of BNCT on patients.

PMID- 22613370
TI  - CAR-T cells and solid tumors: tuning T cells to challenge an inveterate foe.
AB  - Recent reports on the impressive efficacy of adoptively transferred T cells to
      challenge cancer in early phase clinical trials have significantly raised the
      profile of T cell therapy. Concomitantly, general expectations are also raised by
      these reports, with the natural aspiration to deliver this therapy over a wide
      range of tumor indications. Chimeric antigen receptors (CARs) endow T cell
      populations with defined antigen specificities that function independently of the
      natural T cell receptor and permit targeting of T cells towards virtually any
      tumor. Here, we review the current clinical application of CAR-T cells and relate
      clinical efficacy and safety of CAR-T cell trials to parameters considered
      critical for CAR engineering, classified as the three T's of CAR-T cell
      manipulation.

PMID- 22613371
TI  - Different time course of emotion regulation towards odors and pictures: are odors
      more potent than pictures?
AB  - The present study assessed emotion regulation in response to chemosensory and
      visual stimuli. Using cognitive reappraisal, 40 female participants regulated
      their emotions in response to disgusting pictures and odors, while the startle
      reflex was elicited and emotion ratings were assessed. Participants reported
      feeling less negative, and less aroused, while down-regulating their emotions
      towards both odors and pictures. Although being rated as equally negative and
      arousing, odor presentations were accompanied by larger startle responses than
      picture presentations. Furthermore, as compared to pictures emotion regulation
      towards odors followed a strikingly different time course suggesting less
      effective emotion regulation in response to disgusting odors. Questionnaire data
      show that differences between emotion regulation outcome towards odors was not
      attributable to different regulation strategies used. Thus, the current data
      suggest a unique role of olfaction in emotion perception, and show that cognitive
      emotion regulation - although being generally effective - may also be limited.

PMID- 22613372
TI  - [The China Kadoorie Biobank: related methodology and baseline characteristics of
      the participants].
AB  - OBJECTIVE: To study the separate and combined effects of environment, lifestyle,
      physical characteristics, blood biomarkers and genetic factors on aetiology of
      major chronic diseases in adult Chinese. METHODS: China Kadoorie Biobank (CKB) is
      a large blood-based prospective cohort study. The baseline survey took place in 5
      urban and 5 rural areas across China during 2004-2008, with collection of data
      through questionnaire, physical examination and blood samples. Following the
      baseline survey, 5% of the randomly selected participants were surveyed in 2008,
      and repeated every 4-5 years. All participants would be followed for cause
      specific mortality and morbidity through registries and for any hospital
      admission through linkages with health insurance databases. RESULTS: Overall, 512
      891 adults aged 30-79 years (mean 51.5) were recruited, including 41.0% men and
      55.9% from rural areas. Blood collection was successfully done in 99.98% of the
      participants. The prevalence of current regular smoking was 61.3% in men and 2.4%
      in women. The prevalence of regular alcohol consumption (i.e., weekly) was 33.4%
      in men and 2.1% in women. At the baseline, 41.8% of men and 45.3% of women were
      overweight or obese (i.e., BMI>=24.0 kg/m2) and 32.2% of men and 30.2% of women
      were hypertensive (i.e., SBP>=140 mm Hg or DBP>=90 mm Hg). For each of the main
      baseline variables, there were large variations on age, sex and areas of study.
      CONCLUSION: CKB seemed to be a powerful and rich resource in studying the
      environmental and genetic determinants of major chronic diseases in the Chinese
      population.

PMID- 22613373
TI  - [Relationship between serum homocysteine and metabolic syndrome: a cross
      sectional study].
AB  - OBJECTIVE: To explore the relationship between serum homocysteine and metabolic
      syndrome (MS). METHODS: A cohort with 1680 people involved in a community-based
      population in Beijing was investigated. Metabolic syndrome was defined by NCEP
      ATPIII criteria. Multivariate logistic regression analysis was used to estimate
      the odds ratios (OR) of MS. Multiple linear regression analysis was performed to
      analyze the association between Hcy and characteristic variables. RESULTS:
      Homocysteine was higher in MS population compared to those without MS (17.99
      umol/L vs. 17.18 umol/L, P=0.007) after adjusted for age and sex. Levels of
      homocysteine increased with the presence of MS components (from 0 to 4 or 5)
      (16.71, 16.94, 17.62, 18.20, 17.82 umol/L respectively, P=0.044 for linear
      trend). Among the components, groups with larger waist circumference, higher
      blood pressure and triglycerides showed significantly higher Hcy level than their
      counterparts. RESULTS: from multiple logistic regression analysis revealed that
      the highest Hcy quartile (Hcy IV) was significantly associated with MS. Compared
      with the lowest Hcy quartile (Hcy I), the adjusted odds ratio of having MS in
      HcyIV was 1.379 (1.005-1.892) after adjusting for age, sex, levels on
      creatinine/estimated glomerular filtration rate (eGFR)/low-density lipoprotein
      cholesterol (LDL-C) and uric acid, smoking, alcohol intake and exercise. In the
      partial correlation analyses, Hcy was positively associated with body mass index
      (BMI), waist circumsternece, blood pressure, LDL-C, triglycerides (TG), uric
      acid, serum creatinine, eGFR, but inversely associated with high-density
      lipoprotein cholesterol (HDL-C) and independently with age and sex. In multiple
      linear regression analysis, age, male sex, BMI, LDL-C, creatinine and uric acid
      were found to be independently associated with Hcy level. CONCLUSION: There was
      an association noticed between the MS using NCEP-ATPIII criteria and the highest
      quartile level of Hcy in this study. Factors as age and being male, the levels of
      BMI, LDL-C, creatinine and uric acid were independently associated with the Hcy
      level.

PMID- 22613374
TI  - [Multiple correspondence analysis on multiple metabolic abnormalities and family
      history in adults].
AB  - OBJECTIVE: To investigate the relationship between phenomenon of aggregation on
      multiple metabolic abnormalities and their family history. METHODS: A random
      cluster sampling was carried out to study the phenomenon of multiple metabolic
      abnormalities among the adult inhabitants in a county of Henan province.
      Questionnaire, physical examination and biochemical tests were admitted. Multiple
      correspondence analyses were used to explore the aggregation of multiple
      metabolic abnormalities among objects including hyperlipidemia, diabetes,
      coronary heart disease etc. Corresponding relationships between objects and their
      parents on multiple metabolic abnormalities were also analyzed. RESULTS: In
      total, 3901 people were investigated including 1428 (36.6%) males and 2473
      (63.4%) females. The mean age of them was 32.8+/-6.3. Data showed that the
      Cronbach's alpha were 0.547 and 0.387 while Eigen values were 1.971 and 1.535 in
      two dimensions, regarding the correspondence analysis on their parents' multiple
      metabolic abnormalities. Cronbach's alpha levels were 0.598 and 0.457 together
      with Eigen values as 2.263 and 1.743 in two dimensions on the correspondence
      analysis of the objects' and their parents' multiple metabolic abnormalities.
      Results from Multiple correspondence analysis diagrams showed that there was an
      aggregation of variety metabolic abnormalities in both objects and their parents
      but not between objects and their parents or between fathers and mothers, though
      chi2 test showed a weak correlation between some of the categories. The ranges of
      contingency coefficients between metabolic abnormalities were 0.04 to 0.11, 0.04
      to 0.08 and 0.04 to 0.11 between parents, objects and fathers, objects and
      mothers, respectively. When compared with simple obesity, the central obesity
      aggregated appeared more obviously with other metabolic abnormalities.
      CONCLUSION: Both objects and their parents showed an aggregation of variety
      metabolic abnormalities. Aggregation of central obesity showed more obvious on
      other metabolic abnormalities than the simple obesity. Family histories of
      metabolic abnormalities played a moderate role in the generations suffering from
      multiple metabolic abnormalities.

PMID- 22613375
TI  - [Association between body mass index and physical fitness index among children
      and adolescents].
AB  - OBJECTIVE: To explore the relationship between body mass index (BMI) and physical
      fitness index (PFI) among children and adolescents. METHODS: The study sample
      included 8941 students aged 7 to 18 years in Anhui who attended the Physical
      Fitness and Health Surveillance program of Chinese School Students, in 2010.
      Within each sex- and age-specific group, students were classified into five BMI
      categories which were: very low, BMI<5th percentile; low, BMI>=5th but <15th
      percentiles; normal, BMI>=15th but <85th percentiles; high, BMI>=85th but <95th
      percentiles; and very high, BMI>=95th percentiles. Z-scores based on urban-rural,
      sex- and age-specific means and standard deviations were calculated, and the sum
      of Z-scores for the fitness tests was used as a PFI. Differences in PFI between
      BMI categories were compared with ANOVA. Sex- and grade-specific regressions of
      PFI on BMI were done by using a linear model. RESULTS: For 8941 students, the
      PFIs on very low, low, normal, high and very high group were -1.77, -0.91, 0.32, 
      0.17 and -0.54, respectively, and showed an inverted U shape. The normal BMI
      group students presented the highest PFI. Data from Linear regression analysis
      revealed that PFI was significantly positively correlated with BMI, while
      negatively associated with BMI square, which indicated that PFI was the quadratic
      function of BMI. When BMI was increasing, PFI showed a parabolic curvilinear.
      CONCLUSION: Relationships between BMI and PFI were parabolic curvilinear among
      the children and adolescents aged 7 to 18 in Anhui province.

PMID- 22613376
TI  - [Relationship between serum visfatin level and children and adolescent obesity
      and non-alcoholic fatty liver disease].
AB  - OBJECTIVE: To examine the relationships between the level of serum visfatin and
      obesity, nonalcoholic fatty liver disease (NAFLD) in children and adolescents.
      METHODS: Serum visfatin levels of 106 obese children/adolescents (including 49
      non-NAFLD children and adolescents and 57 NAFLD children/adolescents in which
      consisting of 42 mild ones, 15 moderate-to-severe ones) with another 69 lean
      children/adolescents as their controls, were examined by indirect sandwich ELISA.
      RESULTS: When comparing the serum visfatin levels, there was no significant
      difference noticed between the obese group (1.71+/-0.37) ng/ml and the lean group
      (1.75+/-0.37) ng/ml (P=0.455). With the severity of NAFLD, the serum visfatin
      level showed an elevation in obese children and adolescents [obese without NAFLD
      (1.59+/-0.36) ng/ml, obese with mild NAFLD (1.74+/-0.36) ng/ml, obese with
      moderate-to-severe NAFLD (1.97+/-0.36) ng/ml, P<0.05]. In the obese group, serum
      visfatin levels seemed to be related to age (beta=-0.326, P=0.000), alanine
      aminotransferase (ALT) (beta=0.286, P=0.004) and the degree of NAFLD (beta=0.246,
      P=0.014). CONCLUSION: The level of serum visfatin was related to non-alcoholic
      fatty liver in obese children and adolescent.

PMID- 22613377
TI  - [Blood-lipid levels of 20 041 kindergarten children aged 3 to 6 in Tianjin].
AB  - OBJECTIVE: To understand the level of blood-lipid and prevalence of dyslipidemia
      of children aged 3 to 6 in Tianjin, so as to provide evidence for large-scale
      blood screening strategy and to develop intervention of dyslipidemia and
      cardiovascular in children. METHODS: 20,041 children aged 3 to 6 from 48
      kindergartens were involved in this study, in Tianjin. Peripheral blood was
      collected from right leech-finger of these children, after fatless breakfast.
      Total cholesterol (TC) and triglyceride (TG) of plasma were tested using Toshiba
      120 Automatic Biochemical Analyzer. RESULTS: The average levels of TC and TG were
      (4.17+/-0.69) mmol/L and (0.86+/-0.44) mmol/L in these children. 11.4% of the
      children had either TC or TG dyslipidemia, with 7.1% had only TC dyslipidemia,
      4.9% had only TG dyslipidemia, and 0.6% of them had both TC and TG dyslipidemia.
      The prevalence of TC dyslipidemia was significantly higher among girls than boys.
      The prevalence rates of TC dyslipidemia and TG dyslipidemia were different among
      age groups, but with no significant changes among age groups. The prevalence of
      TG dyslipidemia was significantly different, with obese children higher than
      those with normal or overweight children. Different residential areas seemed to
      be related to the difference on the prevalence of dyslipidemia. Prevalence of TC
      dyslipidemia was higher in urban than in rural areas. Prevalence of TG
      dyslipidemia was higher in rural than urban areas. CONCLUSION: The prevalence of
      dyslipidemia for children aged 3 to 6 was high in Tianjin, and showed differences
      among genders, age groups and residential regions. Screening and intervention
      programs on dyslipidemia should be undertaken routinely in children, in order to
      prevent adult atherosclerosis and coronary heart disease.

PMID- 22613378
TI  - [Assessment on dietary iodine intake in three areas of Zhejiang province, 2009].
AB  - OBJECTIVE: To assess the level of dietary iodine intake in three areas of
      Zhejiang and the related policy on universal salt iodization in the province.
      METHODS: The study involved 497 residents from 180 families living in Hangzhou,
      Taizhou, Zhoushan cities, representing coastal and inland areas in Zhejiang
      province in 2009. A total diet study was applied to obtain the typical diet
      samples at three study areas through food consumption, aggregation, sampling and
      preparation processes. The contents of iodine in diet samples were determined by
      tetramethylammonium hydroxide extraction-inductively coupled plasma-mass
      spectrometry. The amount of dietary iodine intake was calculated by timing the
      food consumption data and the iodine content in different dietary samples. The
      safety of dietary iodine intake was evaluated according to the recommended
      nutrient intake (RNI) and tolerable upper intake level (UL) published by the
      Chinese Nutrition Society in 2001. RESULTS: The dietary iodine intake of
      reference person in three areas of Zhejiang province was 421.0 ug/d. The levels
      of P5, P25, median, P75, P90, P95 dietary iodine intake were 145.7 ug/d, 267.6
      ug/d, 358.5 ug/d, 495.6 ug/d, 774.1 ug/d and 1273.0 ug/d respectively. Daily
      dietary iodine intake at <RNI, RNI-UL, >UL accounted for 5.2%, 87.5% and 7.2% of
      all the participants respectively. Without considering the loss through cooking,
      salt iodine provided 81.6% of the dietary iodine source. The resources of dietary
      iodine would include vegetables, cereals and marine food, proportionally, as
      57.2%, 13.0% and 8.5%, respectively. Participants whose daily dietary iodine
      intake exceeded the UL level would consume more marine algae products than those
      whose dietary iodine intakes were lower than RNI or between RNI-UL. CONCLUSION:
      Dietary iodine intake among most residents and their average level were among
      reasonable ranges. Meanwhile, deficiency and excess of iodine intake coexisted.
      Salt iodine was the main resource of dietary iodine. Participants whose dietary
      iodine intakes exceeding the UL level, would prefer consume more marine algae
      products.

PMID- 22613379
TI  - [Risk factors on chronic obstructive pulmonary disease among greenhouse workers
      in Liaoning province].
AB  - OBJECTIVE: To study the risk factors of chronic obstructive pulmonary disease
      (COPD) among greenhouse farmers in Liaoning province. METHODS: According to
      geographical differences in Liaoning province, stratified-cluster-random sampling
      method was used. A total of 5420 greenhouse farmers working in more than 800
      greenhouses were investigated with unified questionnaire, physical examination,
      blood routine examination, blood gas analysis, chest X-ray and pulmonary function
      tests. Diagnosis of COPD was made according to the criteria for "chronic
      obstructive pulmonary disease of diagnosis and treatment guidelines" (2007
      revision) by the Chinese Respiratory Disease Society. RESULTS: The total number
      of farmers under study was 5880, including 5420 respondants (92.18%) with
      effective data. Risk factors were found on age (chi2=32.530, P=0.000), time
      working in greenhouses every day (chi2=21.311, P=0.000), frequency of ventilation
      (chi2=9.791, P=0.007) and the location of the greenhouses (chi2=73.645, P=0.000).
      When using SPSS 17.0 for the single factor logistic regression analysis, results
      indicated that smoking (OR=1.976, 95%CI: 1.672 - 2.334), age (OR=4.188, 95%CI:
      3.718-4.718), greenhouses for fungus (compared with vegetables, OR=1.302, 95%CI:
      1.016-1.669), flowers and plants (compared with vegetables greenhouses, OR=1.503,
      95%CI: 1.201-1.880) were the risk factors of COPD among greenhouse farmers while
      the protective factor was the years of working in the greenhouse (OR=0.684,
      95%CI: 0.609-0.767). CONCLUSION: The overall morbidity of COPD among greenhouse
      farmers in Liaoning province was 17.47% with various risk factors.

PMID- 22613380
TI  - [Suicidal characteristic-clusters for rural young victims aged 15-34 in three
      provinces, China: a case controlstudy].
AB  - OBJECTIVE: To explore the categories on suicide and their characteristic-clusters
      among rural young people of Chinese aged 15-34 in three provinces to provide
      evidence for suicide prevention. METHODS: A total number of 392 suicidal deaths
      and 416 live controls sampled from 16 counties of Shandong, Liaoning, Hunan
      provinces in China, were included in this study. Psychological Autopsy and
      Classification Tree methods were employed. Two informants were interviewed to
      collect the information of each subject. RESULTS: Expectation on future, mental
      disease, seeking guidance and support were important factors for the
      classification of suicide among rural young population, and their scores of
      standardized importance were 100, 97, 91 and 76, respectively. Desperation
      (including feeling about the future and expectation) seemed to be more important
      than mental disease, with 6-8 more scores on standardized importance. Five
      categories of rural young suicides were determined. Desperate people or patients
      with mental disease but with less desperation were the main two categories,
      accounting for 64.8% and 11.8% respectively. Sensitivity and specificity of this
      classification tree were 84.34% and 92.08%, respectively. CONCLUSION: For
      programs on suicide screening and prevention, evaluation on desperation seems
      more significant than screening on mental disease.

PMID- 22613381
TI  - [Study on the unintended pregnancy among married women of child-bearing age
      living in Qingshan district, Wuhan].
AB  - OBJECTIVE: To investigate the prevalence of unintended pregnancy (UP) and
      exploring the risk factors of UP for married women of child-bearing age from
      Qingshan district, Wuhan. METHODS: A cross-sectional study was adopted in this
      study. Cluster sampling method was used with 3256 women recruited, in 2010.
      Information on history and risks related to social-demographic factors of UP were
      collected, using a self-administered questionnaire. RESULTS: Of the 3256
      participants, over half of them (53.8%) reorted ever having had the history of UP
      and 9.1% reported UP in the past year. Rate of UP in the past year for different
      age cohorts (18-30, 31-40, 41-49 years) were 31.8%, 10.5% and 1.8% respectively.
      The most frequently reported reason for UP across all the age cohorts was "Did
      not use any contraceptive methods", with proportions on the reason that reported
      by women at 18-30, 31-40 and 41-49 year-olds, were 69.7%, 51.1% and 42.4%
      respectively. The second frequently reported reasons for UP were "Failure of
      traditional contraception" for younger cohort (18-30 years: 13.0%) and "IUD
      dropped or pregnancy with IUD" for older-age cohorts (23.4% at 31-40 year-olds
      and 37.0% at the 41-49 year-olds). The most frequently cited reason for "Did not
      use any contraceptive methods" was "Believe we were lucky so far, not to get
      pregnant" (59.6%). The risk factors of UP were being at older age, experiencing
      sex debut at younger age and got married at younger age. CONCLUSION: The
      prevalence of lifetime UP history was high among women at child-bearing age from
      Qingshan district, Wuhan. Reproductive health services and interventions should
      be taken according to the needs from different age cohorts of women. Younger
      cohort of women should receive more attention.

PMID- 22613382
TI  - [An epidemiologic study on functional constipation among adult communities in
      Shanghai].
AB  - OBJECTIVE: To determine the prevalence and risk factors of functional
      constipation (FC) by using Rome III criteria in the local adult communities.
      METHODS: A stratified randomized and community-based study by multi-stage cluster
      sampling was employed. A household survey was conducted from April to May 2010.
      All of the participants were interviewed face-to-face by filling out the self
      administered questionnaires which based on Rome III criteria for the diagnosis of
      FC. Self-rating anxiety scale (SAS), self-rating depression scale (SDS) and
      Athens insomnia scale (AIS) were carried out to evaluate the psychological
      characteristics and qualities of sleep. RESULTS: A total of 7648 subjects
      fulfilled the questionnaires, with the response rate as 90.0%. 211 patients met
      the Rome III criteria, including 90 males and 121 females. The adjusted
      prevalence rates of FC were 2.5% in males, 3.3% in females and with an overall
      rate as 2.9%. The ratio of men to women was 1:1.32, with significant difference
      between males and females (P=0.043). The most common group was in the 18-29 year
      olds (chi2=37.359, P=0.000). FC patients were more likely to be detected in the
      group with normal BMI (chi2=16.087, P=0.002), having received high education
      (chi2=27.604, P=0.000), being intelectuals (chi2=6.922, P=0.031) and divorced
      (chi2=22.000, P=0.000) than in other groups. Multivariate analysis showed that
      excessive intake of high-fat food was significantly associated with the presence
      of FC (odds ratio as 1.253, P=0.000), whereas foods with high-fiber (odds ratio
      as 0.854, P=0.029) might serve as protective factors. Significant differences
      between FC groups and control groups were found in the incidence of anxiety (with
      odds ratio as 2.583, P=0.000) and insomnia (odds ratio as 2.443, P=0.000).
      CONCLUSION: The prevalence of FC in adult communities in Shanghai Songjiang
      district was not higher than that in other parts of the communities. Excessive
      intake of high-fat food, anxiety and insomnia might be risk factors for FC and
      foods with high-fiber contents might serve as protective factors.

PMID- 22613383
TI  - [Study on the index system in evaluating the adult health literacy situation
      related to infectious disease in Beijing].
AB  - OBJECTIVE: To establish and assess a comprehensive index system on adult health
      literacy which related to infectious disease. METHODS: A multi-stage stratified
      sampling method was carried out among adults aged over 18 years, in Beijing. A
      questionnaire survey was used to collect the information on adult health literacy
      situation related to infectious disease, with answers scored. Degrees of
      difficulty and difference together with confirmatory factor analysis were used to
      screen the indications from the questionnaires so as to establish a comprehensive
      index system. Methods as Cronbach alpha coefficient, split-half reliability,
      confirmatory factor analysis and cluster analysis methods were used to assess the
      reliability and validity of the index system. RESULTS: The sample size was 13,287
      with valid questionnaires as 13,001. There were 30 indexes selected to establish
      the comprehensive index system on adult health literacy related to infectious
      disease. The Cronbach a coefficient was 0.777, and the split-half reliability was
      0.609. Data from Confirmatory factor analysis revealed that each of the
      standardized regression coefficient was significant, and there were significant
      differences between the groups of being clustered by Q cluster analysis method
      (P<0.001). 9.9% of the residents were classified as having enough knowledge on
      health. CONCLUSION: The index system set for adult health literacy that related
      to infectious disease showed good reliability and validity thus could be used as
      a good tool to evaluate the levels of health literacy which related to infectious
      diseases, in Beijing.

PMID- 22613384
TI  - [Comparison on the antibody response after primary immunization of 5 ug and 10 ug
      hepatitis B vaccine made by recombinant DNA techniques among newborns].
AB  - OBJECTIVE: To compare the antibody response induced by primary immunization with
      5 ug and 10 ug hepatitis B vaccine made by recombinant DNA techniques among the
      newborns. METHODS: Healthy infants who had completed primary immunization with 5
      ug hepatitis B vaccine made by recombinant dexyribonucleic acid techniques in
      Saccharomyces (Hep-SC) or 10 ug hepatitis B vaccine made by recombinant
      dexyribonucleic acid techniques in Hansenula polymorpha (HepB-HP) were included
      in the study. Kids under study were 7-12 months of age and had been on 0-1-6
      schedule. Standardized questionnaire was used and blood samples were collected.
      The titer of antibody to hepatitis B surface antigen (anti-HBs) was detected by
      Chemiluminescence Microparticle Imunoassay (CMIA). If anti-HBs happened to be
      under 10 mIU/ml, HBV DNA was further detected by nested-PCR to distinguish occult
      hepatitis B virus infection. Sero-conversion rate and titer of anti-HBs were
      compared between the two kinds of hepatitis B vaccines. Multivariate analysis was
      used to find the relationship between the kind of hepatitis B vaccine as well as
      the antibody response after debugging the other influencing factors including
      month-age, gender, birth-weight, premature birth and mother's HBsAg status.
      RESULTS: 8947 infants vaccinated with 5 ug HepB-SC and 4576 infants vaccinated
      with 10 ug HepB-HP were investigated. In the 5 ug group, the rates of non-, low-,
      normal- and high-response were 1.88%, 15.18%, 61.42% and 21.52% respectively. In
      the 10 ug group, the corresponding rates were 0.15%, 2.16%, 29.42% and 68.26%
      respectively. The non-, low-, normal-response rates were all higher in 5 ug group
      than in 10 ug group (P<0.01), while the high-response rate was much higher in 10
      ug group than in 5 ug group (P<0.01). The geometric mean concentration (GMC) of
      anti-HBs were 354.81 mIU/ml (95%CI: 338.84-363.08 mIU/ml) and 1778.28 mIU/ml
      (95%CI: 1698.24-1819.70 mIU/ml) in the 5 ug group and 10 ug group respectively.
      The GMC was statistically higher in the 10 ug group than in the 5 ug group
      (P<0.001). The sero-conversion rate and GMC were significantly different between
      the two groups even after debugging the other influencing factors. CONCLUSION:
      Better anti-HBs response could be achieved by primary immunization with 10 ug
      HepB-HP than with 5 ug HepB-SC among newborns.

PMID- 22613385
TI  - [Long term epidemiological effects of vaccination on hemorrhagical fever with
      renal syndrome (HFRS) in Shaanxi provincial HFRS epidemic areas].
AB  - OBJECTIVE: To evaluate the protective rate and the variation of HFRS-IgG on
      hemorrhagical fever with renal syndrome (HFRS) vaccine. METHODS: Cluster, random
      sampling and cross-sectional study were used to assess the protective rate of
      HFRS vaccination. Level of HFRS-IgG was detected with ELISA in epidemic and non
      epidemic areas of HFRS. RESULTS: Curve equation was obtained as Yprotective
      rate=(0.863+0.283/Xvaccination term)*100% by protective rate with vaccination
      term. Protective rates showed a reducing trend, 90% after 7-8 years of
      vaccination, 88% after 10 years, and 94% on average. Absorbance (A) value of HFRS
      IgG was 4 times higher in persons with vaccination than those without, in the
      epidemic area. Higher antibody level could be obtained after primary vaccination,
      but the level of antibody had a 50% reduction after 5-10 years of vaccination,
      and a 60% reduction after 10 years of vaccination. CONCLUSION: HFRS antibody had
      a 50% reduction after 5-10 years of vaccination. The protective rate of HFRS
      vaccination had a 90% loss, after 7-8 years of vaccination. Booster dose was
      necessary after 7 years of vaccination.

PMID- 22613386
TI  - [Association between gestational weight gain and birth weight (2001-2009): a
      cohort study carried outin Kunshan city, Jiangsu province, China].
AB  - OBJECTIVE: To identify the association between gestational weight gain and birth
      weight over the past 9 years in Kunshan city, Jiangsu province, China. METHODS:
      This population-based study was conducted between 2001 to 2009. Data were
      retrieved from Perinatal Monitoring System of Maternal and Child Health Care
      Hospital of Kunshan. The study population consisted of 33 631 women and singleton
      live fetus. Gestational weight gain was defined as the total weight gain during
      the last and first prenatal care program and divided by the interval weeks.
      RESULTS: From 2001 to 2009, the average incidence of low birth weight was 1.86%,
      while the average incidence of macrosomia was a bit higher, fluctuating around
      8.47%. On those underweight mothers, after adjustment for potential confounders,
      and stratified by the BMI levels, which were evaluated at the first prenatal care
      program, we found that weight gain in the 3rd and 4th intervals, could reduce the
      risk of low birth weight (less than 2500 g). With those mothers with normal
      weight, weight gain in the 2 nd, 3 rd and 4th intervals, would reduce the risk of
      low birth weight. Risks in the 4th quantile among underweight and normal-weight
      group were prevalence odds radio (POR) 95%CI: 0.51 (0.32-0.80) and 0.58 (0.42
      0.79), respectively. The risks showed a significant downward trend in underweight
      and normal-weight groups with increased gestational weight gain. As for
      macrosomia (>=4000 g), the risks increased (POR 95%CI) 4.69 (2.82-7.81) in
      underweight, 4.15 (3.43-5.03) in normal-weight, in overweight, 3.64 (2.62-5.06)
      and 1.96 (1.48-2.60) in obese mothers with increased levels of gestational weight
      gain. Trend tests indicated that the risks of marcosomia increased in all levels
      of BMI, with the increase of gestational weight gain. CONCLUSION: Findings from
      this population-based study suggested that gestational weight gain could reduce
      the risks of low birth weight among underweight and normal-weight groups, while
      increase the risks of macrosomia in all parturients, as compared with lowest
      levels of gestational weight gain.

PMID- 22613387
TI  - [Study on HIV-1 drug resistance profile of 257 AIDS patients with failure on the
      first-line antiretroviral treatment in Henan].
AB  - OBJECTIVE: To understand the current situation related to genotypic resistance in
      patients receiving the first-line antiretroviral treatment, but with with
      virologic failure, in Henan province and to compare the patterns of drug
      resistance in patients from different areas. METHODS: 276 patients with virologic
      failure on first-line antiretroviral treatment were selected in three different
      areas of Henan, in 2010. CD4(+)T cells, virus load and genotypic resistance were
      measured and tested. Prevalence and mutations related to drug-resistant were
      analyzed. RESULTS: The overall prevalence of drug-resistance was 68.48% in 257
      patients, with non-nucleoside reverse transcriptase inhibitor (NNRTIs) as 67.70%.
      Rate of nucleoside reverse transcriptase inhibitor (NRTIs) was 54.09%, and
      protease inhibitors (PIs) was 1.18%. The prevalence rates of drug-resistance in
      A, B and C groups were 82.35%, 97.47% and 52.80%, respectively, and withs
      significant differences (chi2=50.624, P=0.000). The Prevalence rates related to
      resistance of NNRTIs and NRTIs were also significantly different (chi2=48.771,
      P=0.000 and chi2=33.912, P=0.000). 26.46% of the samples had M184V/I mutation
      which was the highest NRTIs mutation among the 257 patients. The prevalence rates
      on resistance of A and B were 47.06% and 49.37%, higher than that of C (13.04%,
      chi2=39.905, P=0.000) followed by TAMs, TAMs-1 and TAMs-2 which were 8.56% and
      4.28%. C had the lower prevalence of TAMs-1 than A and B (chi2=13.499, P=0.001).
      40.47% of the samples harbored>=1 TAM, with T215Y/F having the most, as 33.85%.
      31.13% of 257 patients appeared most NNRTIs mutation K103N in this study, with
      the prevalence rates also significant different (chi2=14.213, P=0.001) in the
      three areas. Two PIs mutations were detected in 257 patients: M46I/L, (1.17%) and
      V82F (0.39%). However, none was detected in area A. CONCLUSION: Different
      patterns of drug resistance were found in different areas of Henan province and
      should be treated differently. The work related to AIDS second-line
      antiretroviral therapy in Henan should be more opportune, rigorous and
      standardized.

PMID- 22613388
TI  - [Genetic diversification of avian influenza H5N1 virus in boundary areas of
      Yunnan province].
AB  - OBJECTIVE: To elucidate the genetic diversifications of avian influenza subtype
      H5N1 viruses in the boundary regions of Yunnan province during 2009 to July,
      2011. METHODS: Swab samples were collected from foreign poultry and wild birds in
      boundary regions of Yunnan province during 2009 to July, 2011 and tested by H5/N1
      subtype-specific multiplex RT-PCR. The HA genes of H5N1 virus from the positive
      samples were amplified by RT-PCR and cloned into pMD18-T vectors for sequencing.
      Both alignment and phylogenetic analysis were performed with sequences of the
      known reference strains. RESULTS: Fifteen different HA sequences were obtained
      from 36 representative positive samples and could be divided into 2 distinct
      Clades (2.3.2 and 2.3.4). Through phylogenetic analysis, Clade 2.3.2 and 2.3.4
      could then be further divided into 3 (II-1 to II-3) and 2 smaller clades (I-1 and
      I-2), respectively. The viruses of Clade 2.3.2 II-1 and II-2 were new variant
      strains of H5N1 virus. The cleavage sites of HA from positive samples all
      possessed molecular characterization of highly pathogenic avian influenza virus.
      Mutation of key amino acids had been found among receptor binding sites,
      potential glycosylation sites, neutralizing epitopes and others. CONCLUSION: It
      seemed evident that the H5N1 subtype viruses showed genetic diversifications and
      had undergone the evolution progress of multi-clade (2.3.2, 2.3.4) to single
      calde (2.3.2) in the boundary regions of Yunnan province, during 2009 to July,
      2011.

PMID- 22613389
TI  - [Development of a singleplex PCR assay targeting O-antigen modification genes for
      molecular serotyping of Shigella flexneri].
AB  - OBJECTIVE: To develop a singleplex PCR assay targeting O-antigen modification
      genes for molecular serotyping of Shigella (S.) flexneri. METHODS: Eight pairs of
      primer for O-antigen synthesis and modification genes of S. flexneri were
      designed and used for developing an O-antigen modification gene-specific
      singleplex PCR assay to serotype 14 most common S. flexneri serotypes (1a, 1b,
      1c, 2a, 2b, 3a, 3b, 4a, 4b, 5a, Y, X, Xv and F6). Bacterial pathogens which
      causing diarrheal disease were used for specificity detection. 106 S. flexneri
      clinical isolates were serotyped by this method and compared with the slide
      agglutination method. RESULTS: An O-antigen modification, gene-specific
      singleplex PCR was developed. When six singleplex PCR reactions were performed,
      14 of the 15 recognized S. flexneri serotypes were identified, except for
      serotype Xv. The detection threshold ranged from 10 pg to 1 ng DNA in a 20 ul
      reaction system. A high concordance between the singleplex PCR assay and slide
      agglutination were observed when 106 S. flexneri strains of various serotypes
      were analyzed with an exception that 1 serotype Y strain showed that it was
      carrying the additional defective gtr II genes. CONCLUSION: This method showed
      advantages over the traditional slide agglutination methods, and was promising
      when under application in the following situations as clinical diagnosis.

PMID- 22613390
TI  - [Impact of high-density lipoprotein levels at hospital admission on the outcome
      of patients with acute ST-segment elevation myocardial infarction].
AB  - OBJECTIVE: To analyze the impact of high-density lipoprotein cholesterol (HDL-C)
      levels at hospital admission on the incidence of major adverse cardiovascular
      events (MACCE) in patients with acute ST segment elevation myocardial infarction
      (ASTEMI). METHODS: 1067 patients with ASTEMI who were admitted to the 20
      hospitals in Liaoning region and with lipid profile tested within the 24 hours of
      admission from May 2009 until May 2010, were enrolled. Data on basic demographic,
      clinical, status on admission and method of treatment were collected. Rate on
      various medical use and MACCE (cardiovascular death, non-fatal myocardial
      infarction, revascularization and stoke) were compared between the two groups
      through follow-up observation. Cox proportional hazard analysis was estimation.
      RESULTS: The median HDL-C level was 1.27 mmol/L, with 587 patients having HDL-C
      below and 489 patients HDL-C above the median level. The incidence rates of non
      fatal myocardial infarction and MACCE at one-year follow-up period, was higher in
      low HDL-C group (4.8% vs. 0.9%, P<0.001; 23.7% vs. 18.1%, P=0.03, respectively).
      At one month follow-up, the incidence rate of non-fatal myocardial infarction was
      higher in low HDL-C group (1.4% vs. 0.0%, P=0.01). At six month follow-up, the
      incidence rates of non-fatal myocardial infarction and MACCE on one-year follow
      up was higher in low HDL-C group (2.8% vs. 0.4%, P=0.003; 18.3% vs. 13.7%,
      P=0.04, respectively). RESULTS: from Cox proportional hazards analysis indicated
      that age (HR=1.02, 95%CI: 1.006-1.035, P=0.005), diabetes (HR=1.05, 95%CI: 1.053
      2.171, P=0.03), HDL-C level (HR=0.56, 95%CI: 0.340-0.921, P=0.02) were
      significantly related to the incidence of MACCE. CONCLUSION: The incidence rates
      of one year and six month MACCE (mainly non-fatal myocardial infarction) and one
      month non-fatal myocardial infarction were significant higher in patients with
      low than high HDL-C levels at admission while kept on the ascending along with
      time. Age, diabetes, HDL-C level were independent risk factors related to the
      incidence of MACCE.

PMID- 22613391
TI  - [Comparison on the effects of clopidogrel, statins combination in treating
      coronary artery disease among the elderly patients: a retrospective cohort
      study].
AB  - OBJECTIVE: To compare the effects of clopidogrel with or without combined with
      CYP3A4-metabolized statin in treating coronary artery disease (CAD) among the
      elderly patients. METHODS: The study cohort was defined as all patients were over
      60 years of age and hospitalized for CAD who were prescribed clopidogrel between
      January 2000 and February 2011. A total of 1021 patients were enrolled, with 178
      of them prescribed clopidogrel and 843 patients were administrated clopidogrel
      combined with statins (CYP3A4-metabolized statins 636 and non CYP3A4-metabolized
      statins 207). The primary endpoint was all cause of death and the second endpoint
      were non-fatal myocardial infarction (MI), but hospitalized for unstable angina,
      stroke, transient ischemic attack, or repeated revascularization (PCI or coronary
      artery bypass graft). RESULTS: Among the clopidogrel group and the clopidogrel
      plus statins group, the incidence density of death was 6.86/1000 and 3.18/1000
      respectively, with crude RR as 2.15 (95%CI: 1.39-3.33) and statistically
      significant (chi2=3.53, P<0.01). The incidence density of composite
      thromboembolic events did not show statistical significance (P>0.05). The two
      groups were 1:1 matched, after propensity score matching, clopidogrel
      coadministrated with statins group showed significant decrease in all cause of
      death, with RR as 0.42 (95%CI: 0.19-0.93), chi2=7.23, P<0.01. No significant
      difference was observed in deaths or composite thromboembolic events between
      statins via different cytochrome P450 pathways. CONCLUSION: Clopidogrel with
      statin could reduce the mortality of elderly CAD patients compared with
      clopidogrel without statin. The result did not show statistical significance
      between CYP3A4-metabolized statins or non CYP3A4-metabolized statins regarding
      the mortality or composite endpoint events.

PMID- 22613392
TI  - [Relationship between the 'Real World' research, randomized controlled trial and
      number of one randomized controlled trial in clinical therapeutic study].

PMID- 22613393
TI  - Regional citrate anticoagulation for continuous renal replacement therapy: the
      better alternative?

PMID- 22613394
TI  - Doctor, should I remain on dialysis or accept the ECD kidney offered to me?

PMID- 22613395
TI  - Eliminating racial disparities in access to living donor kidney transplantation:
      how can centers do better?

PMID- 22613396
TI  - Stroke risk in maintenance hemodialysis.

PMID- 22613398
TI  - The newlyweds.

PMID- 22613399
TI  - Quiz page June 2012: kidney failure in an HIV-positive patient.

PMID- 22613401
TI  - Kummell's disease, an uncommon and complicated spinal disorder: a review.
AB  - Kummell's disease is an uncommon and complicated spinal condition first described
      in 1891. Patients develop a kyphosis in the lower thoracolumbar spinal region
      months to years after sustaining an otherwise asymptomatic minor spinal trauma.
      The patho physiology, clinical presentation, imaging and treatment options of
      this disease remain controversial. The most widely accepted hypothetical patho
      physiology is avascular osteonecrosis. The intravertebral vacuum cleft phenomenon
      is considered a radiographic sign of avascular osteonecrosis of the vertebral
      body and is highly suggestive of Kummell's disease. Treatment options include
      nonsurgical and surgical treatment, and percutaneous vertebral augmentation. The
      primary aims of surgical treatment of Kummell's disease are neural decompression
      and stabilization of the spinal column. Surgery can involve an anterior,
      posterior, or combined anterior and posterior approach. Surgery and percutaneous
      vertebral augmentation provide significant symptomatic relief, functional
      improvement and deformity correction. Treatment of this disease must be
      individualized according to the stage of disease and the experience and
      preference of the surgeon.

PMID- 22613400
TI  - Surgery is an effective and reasonable treatment for degenerative scoliosis: a
      systematic review.
AB  - OBJECTIVE: A systematic review to evaluate the role of surgery for treating
      degenerative scoliosis (DS) in terms of improved function (Oswestry Disability
      Index [ODI]) and correction of deformity (Cobb angle); safety outcomes included
      complication and repeat surgery rates. METHODS: A search of the MEDLINE, ISI Web
      of Knowledge and Cochrane Library databases was performed. The methodological
      quality of each study was assessed according to standardized criteria and data
      were extracted. RESULTS: A total of 16 studies including 553 patients with DS met
      the eligibility criteria  for inclusion. The mean ODI score at final follow-up
      was 36.0 +/- 7.8 (304 patients) and the mean decrease in ODI was 23.3 +/- 11.3
      (302 patients). Mean reduction in curve angle (as a percentage of the original
      curve) was 48.5 +/- 21.0% (527 patients). The overall incidence  of complications
      was 49.0% (171 in 349 patients) and the rate of repeat surgery was 15.3% (61 in
      398 patients). CONCLUSIONS: Despite a high incidence of complications and
      reoperations, surgery was an effective and reasonable treatment for DS, providing
      significant functional improvement and deformity correction.

PMID- 22613402
TI  - Current treatment of sacral giant cell tumour of bone: a review.
AB  - Sacral giant cell tumour of bone has an insidious onset and slow growth rate,
      making early diagnosis difficult. The tumour has a high recurrence rate and is
      often fatal. Magnetic resonance imaging and computed tomography (CT), including
      CT-guided fine-needle biopsy, are useful for early  diagnosis. Although therapy
      for sacral giant cell tumour often involves surgical resection and reconstruction
      challenges, improvements in various treatment modalities, including arterial
      embolization and radiotherapy, have widened the effective treatment options. The
      current surgical and adjuvant  treatment modalities available for the management
      of sacral giant cell tumour are systematically reviewed and a suggested treatment
      algorithm is provided. En bloc excision remains the surgical procedure of choice,
      with functional reconstruction important in cases where the lesion is  high in
      the sacrum. The use of adjuvant radiotherapy and chemotherapy remains
      controversial and should be studied further. Determination of the optimum
      treatment for sacral giant cell tumour will require randomized controlled trials.
      Early diagnosis, complete surgical resection with tumour-free  margins and
      comprehensive treatment are important for local tumour control and improved
      outcome.

PMID- 22613403
TI  - Signal transduction pathways and transcriptional mechanisms of ABCB1/Pgp-mediated
      multiple drug resistance in human cancer cells.
AB  - Multiple drug resistance (MDR), defined as the ability of tumour cells to survive
      exposure to many chemotherapeutic agents, is a major cause of treatment failure
      in human cancers. The membrane transporter P-glycoprotein (Pgp, encoded by the
      ABCB1 [adenosine triphosphate-binding  cassette, subfamily B, member 1] gene) is
      the main mechanism for decreased intracellular drug accumulation in human MDR
      cancer. ABCB1/Pgp-mediated MDR involves several signal transduction pathways and
      transcription factors. Activation of these signal transduction pathways
      influences  the prognosis of MDR human cancer. Signalling pathways involved in
      ABCB1/Pgp-mediated MDR include the mitogen-activated protein kinase (MAPK), c-Jun
      NH(2)-terminal kinase (JNK), p38, cyclic adenosine monophosphate-dependent
      protein kinase, phosphatidylino sitol 3-kinase and  protein kinase C signalling
      pathways. This review summarizes the biological characteristics, target points
      and signalling cascade mediators of these pathways. Drugs targeted against these
      pathways may provide new therapies for treatment of ABCB1/Pgp-mediated MDR.

PMID- 22613404
TI  - Social behaviour risk factors for drug resistant tuberculosis in mainland China:
      a meta-analysis.
AB  - OBJECTIVE: To determine risk factors associated with drug resistant tuberculosis
      (TB) in mainland China. METHODS: PubMed and Chinese BioMedical databases were
      searched. Cohort, case-control and cross-sectional studies providing effect
      estimates of risk factors for any-drug resistant  or multidrug resistant (MDR) TB
      were included. RESULTS: The meta-analysis included 16 studies. Any-drug resistant
      TB was significantly associated with poor quality directly observed treatment,
      shortcourse (DOTS) (odds ratio [OR] 2.65, 95% confidence interval [CI] 1.22,
      5.79), long term illness  > 1 year (OR 2.71, 95% CI 1.34, 5.48), poor treatment
      adherence (OR 2.00, 95% CI 1.17, 3.40), previous treatment (OR 4.54, 95% CI 2.71,
      7.61) and age 40 - 60 years (OR 1.62, 95% CI 1.10, 2.38). MDR-TB was
      significantly associated with poor quality DOTS (OR 1.84, 95% CI 1.36, 2.49), 
      poor treatment adherence (OR 4.39, 95% CI 2.97, 6.50), previous treatment (OR
      3.83, 95% CI 2.12, 6.89) and poverty (OR 1.87, 95% CI 1.38, 2.52). CONCLUSIONS:
      Previous treatment, poor quality DOTS, poor treatment adherence, long term
      illness, age 40 - 60 years and poverty are associated  with a greater risk of
      drug resistant TB in mainland China.

PMID- 22613405
TI  - TP53 codon 72 polymorphism with hepatocellular carcinoma: a metaanalysis.
AB  - OBJECTIVE: The association between codon 72 polymorphism of the tumour protein
      p53 (TP53) gene - which results in a missense mutation of arginine (R) to proline
      (P) - and susceptibility to hepatocellular carcinoma (HCC) is controversial. A
      metaanalysis was performed  in order to define this relationship more precisely.
      METHODS: Published studies of TP53 codon 72 polymorphism and the risk of HCC were
      identified. Data were extracted, and summary odds ratios (OR) and 95% confidence
      intervals (95% CI) were calculated. Pooled ORs were determined for  an additive
      model (R/R versus P/P), a dominant model ([R/R + R/P] versus P/P) and a recessive
      model (R/R versus [R/P + P/P]). RESULTS: The meta-analysis included seven case
      control studies (total 1511 cases and 2165 controls). The risk of cancer was
      significantly decreased in the overall  dominant model and the dominant model in
      Asian populations. A significantly decreased risk was found for all models in
      hospital-based but not population-based studies. There was no association between
      polymorphism and cancer risk when data were stratified according to hepatitis B
      or C virus  infection status. CONCLUSION: The TP53 codon 72 polymorphism may be a
      risk factor for HCC.

PMID- 22613406
TI  - Therapeutic and preventive effects of an epidermal growth factor receptor
      inhibitor on oral squamous cell carcinoma.
AB  - OBJECTIVE: Oral squamous cell carcinoma (OSCC) is the sixth most common human
      neoplasm worldwide. Epidermal growth factor receptor (EGFR) is a receptor
      tyrosine kinase that is highly expressed in human OSCC and is a target for cancer
      therapy and prevention. This study investigated the  therapeutic and preventive
      effects of an inhibitor of EGFR (PD153035) on OSCC. METHODS: The effects of
      PD153035 were examined in human cancer cell lines in vitro, in an athymic nude
      mouse xenograft model in vivo, and in the 7,12-dimethyl benz[a]anthracene (DMBA)
      induced  hamster cheek pouch tumour model in vivo. RESULTS: PD153035
      significantly inhibited cell growth, delayed cell cycle progression and induced
      apoptosis in human OSCC cells in vitro. In vivo, PD153035 inhibited xenograft
      tumour growth in nude mice in a dose-dependent manner  and prevented the
      development of OSCC at the postinitiation stage in the DMBA-induced hamster cheek
      pouch tumour model. PD153035 inhibited the DMBA-induced increases in cell
      proliferation and in levels of phosphorylated EGFR and phosphorylated signal
      transducer and activator of transcription  3 (STAT3) protein in the hamster cheek
      pouch. CONCLUSIONS: Inhibitors of EGFR, such as PD153035, have potential value in
      the treatment and prevention of OSCC.

PMID- 22613407
TI  - Increased Expression of MicroRNA-221 in gastric cancer and its clinical
      significance.
AB  - OBJECTIVE: MicroRNA-221 (miR-221), which is located on chromosome X, is an
      oncogenic microRNA that is involved in several human malignancies. This study
      aimed to characterize the role of miR-221 in the initiation and malignant
      progression of gastric cancer. METHODS: The level of miR-221  expression in 92
      pairs of primary gastric tumour tissue and adjacent nontumour tissue was
      quantified by real-time reverse transcription-polymerase chain reaction. The
      relationship between the miR-221 level and clinicopathological features was
      explored. RESULTS: MiR-221 was up-regulated  in 88% (81/92) of gastric cancer
      tissue samples compared with their paired adjacent nontumour tissue samples. High
      expression of miR-221 showed a significant correlation with advanced tumour-node
      metastasis stage, local invasion and lymphatic metastasis. Univariate and
      multivariate  Cox proportional hazard regression analyses revealed that miR-221
      overexpression was an unfavourable prognostic factor for overall survival in
      patients with gastric cancer. CONCLUSIONS: These findings suggest that miR-221 is
      a novel prognostic indicator in gastric cancer and may be a potential  target for
      diagnosis and gene therapy.

PMID- 22613408
TI  - Evaluation of plasma and tissue S100A4 protein and mRNA levels as potential
      markers of metastasis and prognosis in clear cell renal cell carcinoma.
AB  - OBJECTIVES: To investigate levels of S100A4 protein in plasma and S100A4 mRNA in
      tumours from patients with clear cell renal cell carcinoma (CCRCC), and correlate
      these with metastasis, survival and levels of vascular endothelial growth factor
      (VEGF). METHODS: Plasma S100A4 and VEGF protein concentrations were measured
      using enzyme-linked immuno sorbent assays in 39 healthy subjects and 68
      consecutive patients with untreated CCRCC. Levels of S100A4 and VEGF mRNA in
      tumour and matched control (healthy) tissue samples were measured using realtime
      quantitative reverse transcription-  polymerase chain reaction. Findings were
      analysed with respect to clinico pathological characteristics. RESULTS: Plasma
      VEGF concentrations were higher in patients with CCRCC than in healthy subjects.
      S100A4 and VEGF mRNA levels were up-regulated in CCRCC tumour tissue compared
      with control tissue samples. Logistic regression analysis revealed that up
      regulated tumour S100A4 and VEGF mRNA levels were independent risk factors for
      the presence of invasion and/or metastasis. CONCLUSIONS: S100A4 and VEGF are
      associated with tumour invasion and metastasis, and may be useful prognostic
      markers in patients with CCRCC. S100A4 and VEGF may represent potential targets
      for therapeutic intervention.

PMID- 22613409
TI  - Factors affecting the clearance of high-risk human papillomavirus infection and
      the progression of cervical intraepithelial neoplasia.
AB  - OBJECTIVE: This study aimed to identify factors that predict clearance of high
      risk human papillomavirus (HPV) infection and progression to cervical
      intraepithelial neoplasia (CIN) 2 or higher, in women with normal cervical
      histology or CIN 1. METHODS: A retrospective analysis was performed  on 817 high
      risk HPV-infected women with histologically verified CIN 1 or normal cervical
      histology. Patients were followed-up for a maximum of 24 months. Cervical HPV DNA
      tests were performed at every visit. RESULTS: At the end of followup, 648/817
      (79.3%) patients were free from HPV infection  and 66/817 patients (8.1%)
      progressed to CIN 2 or higher. Age, parity, cytology and viral load at diagnosis
      were significantly and inversely associated with HPV clearance. Cytology, viral
      load and presence of CIN 1 lesions were significantly associated with lesion
      progression. CONCLUSIONS: Cytology and high-risk HPV viral load may be useful
      markers for the likelihood of high-risk HPV clearance and lesion progression.
      Histological status, parity and marital status may also be useful factors to
      consider when predicting progression.

PMID- 22613410
TI  - Enhanced T cell immunity by B7-H4 downregulation in nonsmall-cell lung cancer
      cell lines.
AB  - OBJECTIVES: T cell immunity plays a critical role in host immune surveillance of
      tumour cell growth and metastatic spread. This study used small hairpin (sh)RNA
      mediated gene silencing to target VTCN1 (B7-H4) expression in a nonsmall-cell
      lung cancer (NSCLC) cell line (A549)  and evaluated the effects on T cell immune
      activity using an in vitro coculture system. METHODS: VTCN1-specific shRNA
      expressing plasmid was transfected into A549 cells. Mock transfected and empty
      plasmid-transfected A549 cells served as controls. VTCN1 expression in A549 
      cells was determined by reverse transcription-polymerase chain reaction (RT-PCR)
      for VTCN1 mRNA and Western blotting for B7-H4 protein. Transfected A549 cells
      were cocultured with Jurkat cells. Jurkat cells were examined for proliferation,
      apoptosis, cell cycle distribution and  intracellular cytokine mRNA and protein
      levels. RESULTS: VTCN1-specific shRNA efficiently knocked down VTCN1 mRNA and B7
      H4 protein levels in A549 cells. This downregulation led to enhanced Jurkat cell
      proliferation, decreased apoptosis, stimulated cell cycle progression and
      elevated  production of interferon-gamma, interleukin (IL)-10 and IL-2.
      CONCLUSIONS: B7-H4 negatively regulates T cell-mediated antitumour immunity in
      NSCLC.

PMID- 22613411
TI  - The significance of fragile histidine triad protein as a molecular prognostic
      marker of bladder urothelial carcinoma.
AB  - OBJECTIVES: The role and clinical significance of fragile histidine triad (FHIT)
      gene in the pathogenesis of bladder urothelial carcinoma (UC) and the potential
      of Fhit protein as a prognostic biomarker for UC were investigated. METHODS: FHIT
      expression was determined  according to semiquantitative immunohistochemical
      staining for Fhit protein levels in normal bladder and bladder UC tissues.
      Associations between FHIT expression, clinicopathological features and survival
      were evaluated. RESULTS: This study evaluated 42 cases of normal bladder and 125 
      cases of bladder UC; bladder UC cases had a median follow-up of 53.5 months.
      Immuno histochemistry showed that 95.2% of normal cases and 47.2% of bladder UC
      cases, respectively, were positive for Fhit protein; this difference was
      statistically significant. There was a significant association  between negative
      FHIT expression in bladder UC and advanced tumour stage, high pathological grade,
      large tumour size, tumour recurrence and reduced survival time, but no
      association with age, gender, tumour number or tumour shape. CONCLUSIONS: The
      FHIT gene may have an important  role in the pathogenesis of bladder UC and was
      expressed at lower levels in bladder UC compared with normal bladder tissue.
      Using Fhit protein as a biomarker could provide important information about
      patient prognosis.

PMID- 22613412
TI  - Preoperative lanreotide treatment improves outcome in patients with acromegaly
      resulting from invasive pituitary macroadenoma.
AB  - OBJECTIVE: To investigate whether 3 months' preoperative treatment with
      lanreotide improved outcome in newly diagnosed patients with acromegaly resulting
      from invasive pituitary macroadenoma. METHODS: After baseline evaluation,
      untreated patients were randomized to undergo direct transsphenoidal  surgery or
      lanreotide treatment (30 mg via intramuscular injection every 2 weeks, increased
      to 30 mg/week at week 8 if growth hormone nadir > 2.5 MUg/l), for 3 months prior
      to surgery. Tumour shrinkage following lanreotide treatment was analysed. Cure
      was evaluated at 3 months postsurgery  by measuring growth hormone and
      insulinlike growth factor-1 (IGF-1) levels. RESULTS: Preoperative lanreotide
      treatment significantly reduced mean tumour size. Growth hormone and IGF-1 levels
      were lower in the pretreatment group than in the direct surgery group at 3 months
      postsurgery. According  to combined growth hormone and IGF-1 levels,
      significantly more patients were cured by trans-sphenoidal surgery in the
      pretreatment group compared with the direct surgery group (11 of 24 and five of
      25 patients, respectively). CONCLUSIONS: Lanreotide treatment for 3 months before
      trans-sphenoidal  surgery effectively reduced tumour size, and improved surgical
      cure rate, in newly diagnosed patients with acromegaly resulting from invasive
      pituitary macroadenoma.

PMID- 22613413
TI  - An efficacy analysis for nasopharyngeal carcinoma screening of different
      screening intervals.
AB  - OBJECTIVE: To evaluate the impact of different screening intervals on screening
      for nasopharyngeal carcinoma (NPC). METHODS: A Markov model was constructed,
      based on the natural history of NPC. The 5-year mortality rate of NPC was the
      major measurement to evaluate the efficacies of 16 screening strategies.
      Parameters for the model were derived from published literature. RESULTS:
      Screening reduced the 5-year mortality rate for NPC by 20.4 - 43.3%, compared
      with the equivalent rate without screening. The 5 year mortality rate and the NPC
      pick-up rate with strategy A1 (annual screening) were 23.6% and 83.9%,
      respectively. Compared with strategy A1, strategy B1 (annual screening for
      seropositive subjects; biennial screening for seronegative subjects) had a
      similar 5-year mortality rate (24.0%) and a slightly smaller NPC pick-up rate
      (81.7%), but led to a 39.3% reduction in total screenings. Compared with all
      other strategies excluding strategy A1, strategy B1 achieved the lowest 5-year
      mortality rate and the largest NPC pick-up rate. CONCLUSIONS: Strategy B1 had the
      highest efficacy for NPC screening.

PMID- 22613414
TI  - Overexpression of interleukin-18 induces growth inhibition, apoptosis and gene
      expression changes in a human tongue squamous cell carcinoma cell line.
AB  - OBJECTIVE: To investigate the role of interleukin-18 (IL-18) in regulating the
      growth of the human tongue squamous cell carcinoma cell line CRL-1623TM. METHODS:
      The human IL18 gene was cloned and transfected into CRL-1623TM cells using the
      transfection vector pcDNA3.1(+).  Investigations included analysis of cell
      viability, detection of apoptosis using annexin V-fluorescein isothiocyanate,
      assessment of caspase 3/7 activity and real-time reverse transcription-polymerase
      chain reaction to assess expression of the IL18, CCND1 (cyclin  D(1)), CCNA1
      (cyclin A(1)) and IFNG (interferon-gamma) genes. RESULTS: Introduction of the
      IL18 gene inhibited cell proliferation at 24, 48 and 72 h after transfection
      compared with untransfected cells and cells transfected with blank pcDNA3.1(+)
      vector.  Apoptotic cell numbers and caspase 3/7 activity were significantly
      enhanced by IL18 transfection. Levels of IL18 and IFNG mRNA were elevated and
      CCND1 mRNA was reduced after 48 h in IL18 transfected cells compared with wild
      type cells. CONCLUSIONS: These findings suggest that  IL-18 plays a role in the
      regulation of tongue squamous cell carcinoma and may represent a potential
      therapeutic target.

PMID- 22613415
TI  - Stable knockdown of clusterin by vectorbased RNA interference in a human breast
      cancer cell line inhibits tumour cell invasion and metastasis.
AB  - OBJECTIVE: Overexpression of the clusterin (CLU) gene occurs in breast cancer and
      is associated with lymph node metastasis. The present study explored the effect
      of CLU silencing on invasion and metastasis, and the relationship between CLU
      expression and the extracellular  signal-regulated kinase (ERK) / matrix
      metalloproteinase-9 (MMP) signalling pathway in human breast cancer cells.
      METHODS: A pcDNA3.1-based RNA interference approach was used to knockdown the CLU
      gene in MDA-231 cells (MDA-231-CLUi); control MDA-231 cells were transfected with
      an empty vector (MDA-231-Vec). Reverse transcription-polymerase chain reaction
      was used to assess CLU and MMP-9 mRNA levels, and Western blotting was used to
      analyse CLU, MMP-9 and ERK protein levels. Metastatic potential was evaluated
      using in vitro and in vivo models  of invasion and metastasis. RESULTS: Compared
      with MDA-231-Vec cells, the MDA-231-CLUi cells demonstrated reduced migration and
      invasion in vitro and decreased metastatic potential in vivo. Reintroduction and
      reexpression of the CLU gene into the MDA-231-CLUi  cells restored the invasive
      phenotype. MMP-9 mRNA and protein levels were reduced in MDA-231-CLUi cells, and
      there was a correlation between activated ERK and CLU and MMP-9 protein levels.
      CONCLUSION: CLU may regulate the aggressive behaviour of human breast cancer
      cells through  modulation of ERK signalling and MMP9 expression.

PMID- 22613416
TI  - Increased numbers of T helper 17 cells and the correlation with
      clinicopathological characteristics in multiple myeloma.
AB  - OBJECTIVE: T helper 17 (Th17) cells play important roles in adaptive immunity and
      are involved in several inflammatory and autoimmune diseases, but little is known
      about their role in tumour immunity. The current study investigated the
      involvement of Th17 cells in multiple myeloma. METHODS: Flow cytometry was used
      to investigate the frequencies of Th17 cells in peripheral blood mononuclear
      cells from 30 patients with multiple myeloma and from 14 healthy control
      subjects. The concentrations of Th17-associated cytokines (interleukin [IL]-6, IL
      17, IL-1beta and IL-23)  were measured by enzyme-linked immunosorbent assay.
      RESULTS: There was a significantly increased proportion of Th17 cells, and
      increased plasma concentrations of Th17-associated cytokines, in patients with
      multiple myeloma compared with healthy controls. There was a significant
      relationship  between the proportion of Th17 cells and clinical tumour stage,
      serum lactate dehydrogenase concentration and serum creatinine concentration.
      CONCLUSIONS: Th17 cells might be important therapeutic targets in multiple
      myeloma and could facilitate a better outcome for tumour immunotherapy.

PMID- 22613417
TI  - Effect of endoscopic sinus surgery on plasma asymmetric dimethylarginine levels
      in patients with extensive nasal polyposis.
AB  - OBJECTIVE: This study examined the effect of endoscopic sinus surgery (ESS) on
      plasma levels of asymmetric dimethylarginine (ADMA) and mean pulmonary arterial
      pressure (mPAP) in patients with extensive nasal polyposis (ENP). METHODS:
      Preoperative and 3 month post-ESS plasma levels of ADMA and mPAP were measured in
      patients with ENP and in age-and gender-matched controls. RESULTS: The study
      included 45 patients with ENP and 31 controls (mean +/- SD age 39.4 +/- 8.8 and
      38.1 +/- 9.6 years, respectively). The mean preoperative ADMA level in ENP
      patients (0.69 +/- 0.27 MUmol/l) was statistically significantly lower than in
      the control group (1.08 +/- 0.37 MUmol/l). The postoperative ADMA level increased
      significantly in ENP patients (0.97 +/- 0.36 MUmol/l) versus the preoperative
      level. Mean preoperative mPAP in ENP patients (25.7 +/- 5.4 mmHg) was
      statistically significantly higher than in the control group (20.8 +/- 2.1 mmHg),
      and ENP patients showed significant decreases in mPAP after (21.9 +/- 3.5 mmHg)
      versus before ESS. CONCLUSION: Patients with ENP had lower plasma ADMA levels
      compared with healthy controls, however ADMA levels and mPAP improved in ENP
      patients after ESS.

PMID- 22613418
TI  - Effects of liver function on ionized hypocalcaemia following rapid blood
      transfusion.
AB  - OBJECTIVE: Hypocalcaemia detrimentally affects the cardiovascular system and
      massive transfusion-related hypocalcaemia is particularly severe in end-stage
      liver disease patients undergoing liver transplantation (LT). This study,
      therefore, compared the severity and duration of ionized  hypocalcaemia between
      patients with normal and impaired liver function. METHODS: Patients (n = 26 per
      group) were transfused at a rate of 10 ml/kg within 10 min with packed red blood
      cells (PRBCs) during LT (group LP) or spinal surgery (group SP), or were infused
      with 0.9% normal saline  during spinal surgery (group SN). Serum levels of
      ionized calcium were assessed before (T(0)), just after (T(1)), and at 20 (T(2))
      and 60 min (T(3)) after transfusion. RESULTS: Transfusion with PRBCs caused more
      severe ionized hypocalcaemia than 0.9% normal  saline at T(1). In contrast to the
      faster (20 min) normalization in group SP, ionized hypocalcaemia in group LP
      persisted at T(3). Serum ionized calcium levels at T(3) showed correlations with
      vital signs, blood glucose, serum potassium, base deficit and lactate.
      CONCLUSION: Rapid blood transfusion caused more severe and prolonged ionized hypo
      calcaemia in patients with liver dysfunction than in those with normal liver
      function.

PMID- 22613419
TI  - Adipocytokines and insulin resistance across various degrees of glucose tolerance
      in pregnancy.
AB  - OBJECTIVE: Gestational diabetes mellitus is characterized by progressive insulin
      resistance. Adipocytokines are thought to be associated with insulin resistance.
      This cross-sectional study evaluated the associations between serum
      concentrations of several adipocytokines and insulin resistance at different
      stages of glucose tolerance in pregnancy, using the homeostasis model assessment
      of insulin resistance (HOMA-IR) as a reference. METHODS: According to oral
      glucose tolerance test results, 74 pregnant women were divided into three groups:
      normal glucose tolerance (n = 25); intermediate glucose tolerance (n = 19);
      gestational diabetes mellitus (n = 30). Adiponectin, leptin, resistin, visfatin
      and retinol-binding protein 4 (RBP4) concentrations were measured using enzyme
      linked immuno sorbent assays. RESULTS: Groups were comparable regarding age, week
      of gestation and body mass index before gestation. There were statistically
      significant between-group differences in HOMA-IR, but no significant differences
      regarding serum adipocytokine concentrations. CONCLUSIONS: Adipo nectin, leptin,
      resistin, visfatin and RBP4 were not associated with the degree of glucose
      tolerance in pregnancy. Concentrations of these adipocytokines are not
      sufficiently sensitive to replace HOMA- IR in pregnancy.

PMID- 22613420
TI  - The influence of different movements on ambulatory blood pressure in hypertensive
      subacute stroke patients.
AB  - OBJECTIVE: This study evaluated variation in blood pressure (BP) in hypertensive
      subacute stroke patients performing eight different types of active movement, and
      variations in BP over time. METHODS: The study included 35 subacute stroke
      patients (60 - 74 years old) and 15 age-matched  healthy volunteers. Ambulatory
      systolic and diastolic BP was measured over 4 consecutive days, before and during
      active movement. RESULTS: The greatest effect of the different active movements
      in stroke patients was on mean systolic BP variability (BPV). There was a
      significant difference  in systolic and diastolic BPV between stroke patients at
      different time-points and compared with healthy volunteers. Systolic BPV during
      shifting from the ward to the rehabilitation centre was significantly higher than
      for all other active movements. Mean systolic BPVs during the sessions  on the
      first and second days were significantly higher than for the sessions on the
      third and fourth days in stroke patients and compared with healthy volunteers.
      CONCLUSIONS: Systolic BP was found to be increased in hypertensive subacute
      stroke patients during their first and/or second attempts  at performing active
      movements. Therapists should consider the BP of hypertensive subacute stroke
      patients during these first two attempts, especially for activities involving the
      patient moving from the ward to the rehabilitation centre.

PMID- 22613421
TI  - Sleep apnoea syndrome as a risk for mortality in elderly inpatients.
AB  - OBJECTIVE: The characteristics of sleep apnoea syndrome (SAS) in the elderly,
      including subtype classification and association with mortality, have not been
      fully elucidated. This study examined these factors in an elderly Japanese
      inpatient population. METHODS: Overnight polysomnography was used to diagnose and
      classify SAS in 145 elderly inpatients (mean +/- age 81 +/- 8 years). Clinical
      data, including brain computerized tomography findings, were recorded. The study
      population included nine inpatients with obstructive SAS, 12 with central SAS, 25
      with mixed SAS and 99 controls (no SAS). RESULTS: Increased body mass index and
      grade of aortic arch calcification independently contributed to risk of all
      subtypes of SAS combined. There was an independent association between SAS and
      increased risk of mortality from all causes as well as from pneumonia and from
      cardiovascular disease. Only mixed SAS was independently and positively
      associated with increased risk of death from pneumonia. CONCLUSIONS: Obstructive,
      central and mixed SAS were associated with increased risk of cardiovascular
      related and all-cause mortality. Mixed SAS was associated with an increase in
      mortality from pneumonia. There was no relationship between mortality and
      severity of SAS.

PMID- 22613422
TI  - Incidence and risk factors for cognitive dysfunction in patients with severe
      systemic disease.
AB  - OBJECTIVE: To determine the relevance of surgery and other causative factors to
      the incidence of postoperative cognitive dysfunction (POCD) in patients with
      severe systemic disease. METHODS: This observational study included 107
      noncardiac surgical patients and 26 nonsurgical control  subjects, all of whom
      had an American Society of Anesthesiologists physical classification status of 3.
      Cognitive assessment was performed preoperatively and 7 days postoperatively, or
      with a 7-day interval for the control group. POCD was calculated as a combined Z
      score. Mini Mental  State Examination (MMSE) was used to exclude patients with
      pre-existing cognitive deficit (MMSE score <= 23). Surgical and other factors
      including duration of surgery/anaesthesia and length of stay in the intensive
      care unit (ICU) were recorded. RESULTS: After 7 days, POCD was found in 40/107 
      (37.4%) surgical patients compared with 4/26 (15.4%) nonsurgical controls.
      Preoperative MMSE score, duration of surgery/anaesthesia, and length of stay in
      the ICU and hospital were associated with POCD. Logistic regression analysis
      revealed that preoperative MMSE score was an independent predictor  of POCD.
      CONCLUSION: Lower baseline MMSE score was the only independent predictor for POCD
      in patients with severe systemic disease.

PMID- 22613423
TI  - Serum concentrations of resistin and adiponectin and their relationship to
      insulin resistance in subjects with impaired glucose tolerance.
AB  - OBJECTIVES: This study measured the serum concentrations of resistin and
      adiponectin in Chinese subjects with impaired glucose tolerance (IGT) and
      investigated their association with insulin resistance, metabolic parameters and
      circulating inflammatory markers. METHODS: A total of 124  subjects participated
      in the study (44 with IGT and 80 with normal glucose tolerance [NGT]). Fasting
      serum concentrations of lipids, glucose, insulin and adipocytokines (resistin,
      adiponectin, leptin, tumour necrosis factor-alpha [TNF-alpha], interleukin-6 and
      C-reactive  protein) were measured. RESULTS: Serum resistin concentrations were
      similar in the IGT and NGT groups but were significantly higher in overweight/
      obese IGT subjects than in those of normal weight. Serum adiponectin
      concentrations were significantly lower in the IGT group than in the NGT group. 
      In the IGT group, resistin was positively correlated with age, body mass index
      and TNF-alpha, and adiponectin was correlated positively with high-density
      lipoprotein cholesterol and negatively with TNF-alpha and waist/hip ratio.
      CONCLUSIONS: Circulating resistin is unlikely  to be a major mediator of glucose
      tolerance in humans but it may have an inflammatory role in IGT. The data support
      the theory that circulating adiponectin has an anti-inflammatory and anti-insulin
      resistance function.

PMID- 22613424
TI  - Clinical utility of serum matrix metalloproteinase-2 and tissue inhibitor of
      metalloproteinase-2 concentrations in the assessment of liver fibrosis due to
      chronic hepatitis B.
AB  - OBJECTIVE: To explore the relationships between serum concentrations of tissue
      inhibitor of metalloproteinase-2 (TIMP-2) and matrix metalloproteinase-2 (MMP-2),
      and severity of liver fibrosis in chronic hepatitis B. METHODS: A total of 101
      patients with hepatitis B and 54 healthy control  subjects were consecutively
      enrolled. Serum MMP-2 and TIMP-2 were quantified by enzyme-linked immunosorbent
      assay. RESULTS: Serum MMP-2 concentrations in patients with stage F2 - F4
      fibrosis were significantly higher than in patients with stage F0 - F1 fibrosis
      and control subjects,  but no significant difference was found between patients
      with stage F0 - F1 fibrosis and control subjects. Significant differences in
      serum TIMP-2 concentrations were found between patients with stages F2 - F4 and
      F0 - F1 fibrosis, and between stages F0 - F1 fibrosis  and healthy control
      subjects. Areas under the receiver operating characteristic curves of serum TIMP
      2 and MMP-2 for predicting clinically significant fibrosis (stage F2 - F4) were
      0.899 and 0.770, respectively. CONCLUSION: Serum TIMP-2 and MMP-2 assessment may
      represent a valuable noninvasive  diagnostic test for liver fibrosis in hepatitis
      B.

PMID- 22613425
TI  - Mean peak systolic velocity of the superior thyroid artery is correlated with
      radioactive iodine uptake in untreated thyrotoxicosis.
AB  - OBJECTIVE: To evaluate the correlation between mean superior thyroid artery peak
      systolic velocity (STA-PSV) and radioactive iodine uptake (RAIU) in Chinese
      patients with untreated thyrotoxicosis, using retrospectively and prospectively
      collected data. METHODS: Patients with untreated  thyrotoxicosis (n = 220) and
      euthyroid control subjects (n = 30) underwent thyroid function, thyroid
      autoantibody and thyroid ultrasonography tests. Mean STA-PSV was measured by
      ultrasonography. RAIU tests identified 168 patients with Graves' disease and 52
      with destructive  thyroiditis. Linear correlation of mean STA-PSV with 3-h and 24
      h RAIU, and sensitivity, specificity and receiver operating characteristic (ROC)
      curves for mean STA-PSV in the differential diagnosis of Graves' disease and
      destructive thyroiditis were calculated. RESULTS: Mean STA-PSV  was significantly
      higher in Graves' disease than in destructive thyroiditis. Mean STA-PSV
      correlated positively and significantly with 3-h and 24-h RAIU. Area under the
      ROC curve of mean STA-PSV for the differential diagnosis of Graves' disease and
      destructive thyroiditis was 0.825  (optimum cut-off value of mean STA-PSV, 45.25
      cm/s; sensitivity, 80.4%; specificity, 81.4%). CONCLUSIONS: Detection of mean STA
      PSV by ultrasonography agrees with RAIU and is useful for the differential
      diagnosis of thyrotoxicosis in Chinese patients.

PMID- 22613426
TI  - Elevated serum concentrations of inflammatory cytokines and chemokines in
      patients with haemorrhagic fever with renal syndrome.
AB  - OBJECTIVE: Prospective case-control study, undertaken to investigate serum
      cytokine and chemokine concentrations during all clinical phases and in different
      clinical types of haemorrhagic fever with renal syndrome (HFRS). METHODS: Serum
      was collected at various disease phases  from patients with HFRS (n = 35) and
      healthy control subjects (n = 10). Tumour necrosis factor (TNF)-alpha,
      interleukin (IL)-6, IL-4, interferon (IFN)-gamma, IL-8, interferon inducible
      protein-10 (IP-10) and chemokine (C-C motif) ligand 5 (also known as  'regulated
      upon activation, normal T-cell expressed and secreted' [RANTES]) were quantified
      using commercial enzyme-linked immunosorbent assay kits. RESULTS: Serum
      concentrations of TNF-alpha, IL-6, IFN-gamma, IL-8, IP-10 and RANTES (but not IL
      4) were significantly higher  in patients compared with controls. Highest
      concentrations were generally found during the febrile, hypotensive and oliguric
      disease phases, as well as in clinically severe and critical cases. CONCLUSION:
      Serum concentrations of proinflammatory cytokines and chemokines increased in
      line with  disease severity in HFRS patients.

PMID- 22613427
TI  - Spinal-general anaesthesia decreases neuroendocrine stress response in
      laparoscopic cholecystectomy.
AB  - OBJECTIVE: A randomized clinical study to compare the stress response to
      laparoscopic cholecystectomy during spinal-general anaesthesia and epidural-
      general anaesthesia. METHODS: Women undergoing elective laparoscopic chole
      cystectomy were assigned to receive either spinal anaesthesia (SA group; n = 12)
      or epidural anaesthesia (EA group; n = 12), in addition to general anaesthesia.
      Plasma concentrations of cortisol, adrenocorticotrophic hormone (ACTH),
      noradrenaline, adrenaline and total catecholamines were measured pre- and
      intraoperatively. RESULTS: Intraoperative cortisol, noradrenaline and total
      catecholamine levels were significantly lower in the SA group compared with the
      EA group. When pre- and intraoperative values were compared, the SA group showed
      a decrease in adrenaline, noradrenaline and total catecholamine levels, and the
      EA group showed an increase in ACTH and noradrenaline levels. CONCLUSIONS: The
      type of regional anaesthesia significantly affected the stress response: spinal
      anaesthesia produced a more favourable endocrine response than epidural
      anaesthesia. Spinal-general anaesthesia may reduce postoperative morbidity in
      laparoscopic cholecystectomy.

PMID- 22613428
TI  - The effects of intrathecal morphine on patient-controlled analgesia, morphine
      consumption, postoperative pain and satisfaction scores in patients undergoing
      gynaecological oncological surgery.
AB  - OBJECTIVE: Gynaecological oncological surgery (GOS) includes a wide variety of
      surgical procedures and postoperative pain is a major concern. This study
      compared the impact of intrathecal morphine (ITM) plus patient-controlled
      analgesia (PCA) with PCA alone on morphine consumption,  pain relief and patient
      satisfaction after GOS. METHODS: Sixty women undergoing GOS under general
      anaesthesia were randomized to receive either 0.3 mg ITM or placebo. On arrival
      at the postanaesthesia care unit each patient received a morphine PCA pump. The
      three primary outcome measures were  pain, patient satisfaction scores evaluated
      using a 100-mm visual analogue scale and cumulative PCA morphine consumption.
      RESULTS: No significant differences were observed in the demographic data.
      Cumulative PCA morphine consumption was significantly lower in the ITM group
      compared with the  control group. Fatigue scores were lower in the ITM group
      compared with the control group but did not reach statistical significance. Pain,
      sedation and patient satisfaction scores, and the rate of side-effects were
      similar for the two groups. CONCLUSIONS: Administering ITM in GOS could improve 
      postoperative analgesia and reduce morphine consumption without serious side
      effects.

PMID- 22613429
TI  - Prevalence of the metabolic syndrome in the Yan-an region of northwest China.
AB  - OBJECTIVES: To evaluate the prevalence of the metabolic syndrome in a sample
      population from northwest China, and to determine the optimal cut-off point for
      waist circumference for diagnosing the metabolic syndrome in this population.
      METHODS: A total of 1290 residents of the Yan-an region of China completed a
      cross-sectional survey, physical examination and laboratory tests. The
      International Diabetes Federation (IDF), Chinese Diabetes Society (CDS), and the
      National Cholesterol Education Program Adults Treatment Panel-III (NCEP-ATPIII)
      criteria were used to assess the prevalence of the metabolic syndrome and its
      relationship with age and gender. RESULTS: According to the NCEP-ATPIII, CDS and
      IDF diagnostic criteria, the prevalence of the metabolic syndrome was 15.8%,
      20.4% and 26.4%, respectively. The optimal cut-off point for waist circumference
      was >= 86.5 cm for men and >= 80.5 cm for women. CONCLUSIONS: The prevalence of
      the metabolic syndrome in the Yan-an region was significantly higher than that in
      other regions of China, and participants with the metabolic syndrome were much
      younger than those in other Chinese regions.

PMID- 22613430
TI  - Frequent SLIT2 promoter methylation in the serum of patients with ovarian cancer.
AB  - OBJECTIVE: The slit homologue 2 (SLIT2) gene is a tumour suppressor gene. This
      study investigated the methylation status of the SLIT2 promoter in women with
      ovarian cancer in terms of identifying whether this might aid the early diagnosis
      of ovarian cancer. METHODS: Using  methylation-specific polymerase chain reaction
      analysis, the methylation status of the SLIT2  promoter was measured in tumour
      tissue and serum samples from 36 patients with ovarian cancer and in matched
      serum samples from 25 controls without cancer. RESULTS: Aberrant methylation of 
      the SLIT2 promoter was present in ovarian tissue from 29/36 (80.6%) ovarian
      cancer patients, but not in the 25 healthy controls. Among the cases with
      hypermethylation in their ovarian tissue, 27/29 (93.1%) of the case-matched serum
      DNA samples, including all four cases of early-stage  ovarian cancer, showed
      hypermethylation of the SLIT2 promoter. CONCLUSIONS: Hypermethylation of the
      SLIT2 promoter may be a relatively early event in ovarian cancer; thus, its
      detection may be an effective approach to improve early diagnosis.

PMID- 22613431
TI  - Relationship between endothelial nitric oxide synthase, insulin resistance and
      macrovascular disease in patients with acute myocardial infarction.
AB  - OBJECTIVE: To explore the relationship between endothelial nitric oxide synthase
      (eNOS) activity, insulin resistance and macrovascular disease in patients with
      acute myocardial infarction (AMI). METHODS: AMI patients were grouped according
      to the presence (group A, n = 49) or  absence (group B, n = 48) of macrovascular
      disease. A healthy control group was also recruited (group C, n = 43). eNOS
      activity and nitric oxide (NO), endothelin-1 (ET-1), fasting plasma glucose and
      fasting insulin levels were compared across groups. The homeostasis model
      assessment  of insulin resistance (HOMA- IR) was calculated in each participant
      and correlations between biochemical parameters were determined. RESULTS: eNOS
      and NO levels were significantly lower in group A compared with the other groups.
      Conversely, ET-1 levels and the HOMA-IR were significantly  higher in group A.
      eNOS activity and NO levels were significantly lower, and ET-1 levels and HOMA-IR
      were significantly higher, in group B compared with controls. Across the groups
      there were inverse correlations in AMI patients between eNOS and HOMAIR, NO and
      HOMA-IR, eNOS and ET-1, and NO  and ET-1, and positive correlations between eNOS
      and NO, regardless of whether macrovascular disease was present. CONCLUSION:
      There is a close relationship between eNOS activity and the development of
      insulin resistance and macrovascular disease in AMI patients.

PMID- 22613432
TI  - H-reflex and clinical examination in the diagnosis of diabetic polyneuropathy.
AB  - OBJECTIVES: To determine among adult patients with type-2 diabetes mellitus the
      proportion diagnosed with diabetic polyneuropathy (DPN) by clinical evaluation
      and by the Hoffmann reflex (H-reflex). In addition, the predictive value of the H
      reflex in the diagnosis of DPN was evaluated. METHODS: Studies were carried out
      on 150 adult patients referred for neuropathy screening. Diagnostic criteria for
      DPN were at least two abnormalities in clinical neurophysiological examinations
      and electrophysiological testing (H-reflex and nerve conduction velocity).
      Logistic regression analysis was performed to identify unique contributions of
      study characteristics to positive versus negative outcomes. RESULTS: H-reflex was
      absent in 39.3% (59/150) and latency was prolonged in 43.3% (65/150) of patients.
      Ulnar nerve motor branch nerve conduction showed prolonged latency in 9.3%
      (14/150) of patients. Logistic regression analysis indicated that the H-reflex
      was significantly associated with positive outcomes. CONCLUSION: The H-reflex
      could have a predictive value in DPN, providing more quantitative information
      regarding diagnosis than conventional nerve conduction studies.

PMID- 22613434
TI  - Increase in total antioxidant capacity of plasma despite high levels of oxidative
      stress in uncomplicated type 2 diabetes mellitus.
AB  - OBJECTIVE: Oxidative stress is implicated in the pathophysiology of diabetes
      mellitus and its chronic complications. The aim of this study was to evaluate
      plasma antioxidant status in patients with uncomplicated type 2 diabetes, in
      order to understand the interactions between its components  and the diabetic
      milieu. METHODS: Plasma samples were collected from 15 patients with type 2
      diabetes receiving oral antidiabetic agents and from 18 healthy control subjects
      without diabetes. Glycosylated haemoglobin was measured as an indicator of blood
      glucose control. Total and residual  antioxidant activities were measured. Lipid
      peroxides were measured as indicators of plasma oxidative stress. Copper and
      caeruloplasmin were also assayed as possible pro-oxidants. RESULTS: Antioxidant
      activities, lipid peroxide level, copper concentration and caeruloplasmin
      activity were significantly  increased in the plasma of patients with diabetes
      compared with control subjects. CONCLUSIONS: The total antioxidant capacity of
      plasma was increased, despite high levels of oxidative stress, in patients with
      uncomplicated type 2 diabetes. Increased levels of copper and caeruloplasmin
      characterized  the diabetic milieu, despite an absence of chronic complications.

PMID- 22613435
TI  - Comparison of hippocampal volume measured using magnetic resonance imaging in
      Alzheimer's disease, vascular dementia, mild cognitive impairment and
      pseudodementia.
AB  - OBJECTIVE: To examine the relationship between different types of dementia and
      hippocampal volume. METHODS: Hippocampal volume was measured by magnetic
      resonance imaging in patients with Alzheimer's disease (n = 22), vascular
      dementia (n = 14), mild cognitive impairment  (n = 12) or pseudodementia (n =
      16), and in healthy control subjects (n = 11). The Mini Mental State Examination
      was used to stratify subjects according to cognitive function. RESULTS:
      Hippocampal volume was reduced by 42% in Alzheimer's disease, 21% in vascular
      dementia,  15% in mild cognitive impairment and 13% in pseudodementia compared
      with controls. The severity of dementia increased in line with decreasing
      hippocampal volume. CONCLUSIONS: Measurement of hippocampal volume may facilitate
      differentiation between dementia subtypes. There was a relationship  between
      reduced hippocampal volume and the degree of cognitive impairment.

PMID- 22613433
TI  - Single-port laparoscopic hysterectomy versus conventional laparoscopic
      hysterectomy: a prospective randomized trial.
AB  - OBJECTIVE: To compare transumbilical single-port laparoscopic hysterectomy
      (TSPLH) with traditional four-port total laparoscopic hysterectomy (TLH).
      METHODS: Patients with benign uterine disease were assigned to receive either
      TSPLH (n = 52) or TLH (n = 56). Duration of  surgery, intraoperative blood loss,
      conversion rate, time to first flatus, duration of immobilization, post operative
      analgesia requirement, port site infection, port hernia, duration of hospital
      stay, postoperative fever rate and percentage patient satisfaction were recorded.
      RESULTS: TSPLH  and TLH were both performed successfully. TSPLH was associated
      with significantly longer duration of surgery, shorter duration of
      immobilization, lower rate of port site infection and higher patient satisfaction
      than TLH. There were no other significant differences between the two groups. 
      All subjects recovered fully and no postoperative complications occurred during a
      6-month (minimum) follow-up period. CONCLUSIONS: TSPLH was found to be a feasible
      and safe approach for laparoscopic hysterectomy.

PMID- 22613436
TI  - Ageing challenges the results of any outcome study: how to address the effects of
      ageing on activities of daily living.
AB  - OBJECTIVES: Clinical study results might be substantially biased by the effects
      of ageing, resulting in considerable underestimation of treatment efficacy,
      especially when assessing activities of daily living (ADL) in elderly people.
      This study aimed to define age- and comorbidity-related  normative values in ADL.
      METHODS: In cross-sectional sampling, 23 763 German-speaking Swiss individuals
      were contacted. Valid questionnaires from 16 191 (68%) eligible individuals >= 18
      years of age were included in the study. Age-related ADL reference values were
      calculated using questionnaire  data. RESULTS: The sample was representative of
      the German-speaking Swiss population as determined by 2003 census data. Age- and
      pain-related ADL reference values were plotted and confirmed that disability
      increased with increasing age. CONCLUSIONS: The use of ADL scales that provide
      age-  and comorbidity-related reference values for outcome studies or studies
      focusing on the elderly is recommended in order to reduce the effect of bias.

PMID- 22613437
TI  - Adenosine triphosphate content in human unfertilized oocytes, undivided zygotes
      and embryos unsuitable for transfer or cryopreservation.
AB  - OBJECTIVE: To investigate the relationship between adenosine triphosphate (ATP)
      content and developmental potential in human oocytes, zygotes and embryos.
      METHODS: ATP content was determined using a bioluminescence assay in 72
      unfertilized oocytes, 26 undivided zygotes and 70 embryos  unsuitable for
      transfer or cryopreservation, obtained from 52 women undergoing in vitro
      fertilization and embryo transfer (IVF-ET). RESULTS: The mean ATP content
      increased with development: zygotes had a significantly higher ATP content than
      oocytes, and embryos had a significantly  higher ATP content than both zygotes
      and oocytes. Within the embryo group, the ATP content was significantly higher in
      polypronuclear embryos than in inferior embryos with substantial fragmentation.
      When analysed in relation to IVF-ET outcome, the ATP content of oocytes and
      embryos from  women who became pregnant was significantly higher than in oocytes
      and embryos from those who did not become pregnant. CONCLUSIONS: Reduced ATP
      content may be related to fertilization failure, arrested division and abnormal
      embryonic development. The differences observed in oocyte and embryo  ATP content
      between women who became pregnant and those who did not suggests that
      mitochondrial function is correlated with individual fertility.

PMID- 22613438
TI  - Climatic factors correlate with innate immune response in children with
      Dermatophagoides farinae-induced allergic asthma.
AB  - OBJECTIVE: To determine the effect of climatic factors on immune markers in
      children with Dermatophagoides farinae induced asthma. METHODS: Serum
      concentrations of macrophage migration inhibitory factor (MIF), eosinophil
      cationic protein (ECP) and D. farinae-specific immunoglobulin  E (DF-sIgE),
      together with peripheral blood eosinophil counts, were measured in children with
      D. farinae induced (n = 75) or non-D. farinae-induced asthma (n = 17), and in
      healthy controls (n = 30). Mean temperature and relative humidity in the month
      before  enrolment were calculated from meteorological data. RESULTS: MIF, ECP and
      eosinophil counts were significantly higher in children with D. farinae-induced
      asthma than in controls, but comparable with non-D. farinae-induced asthma.
      Children with D. farinae-induced asthma  in a low temperature (< 16  degrees C)
      or low relative humidity (< 70%) climate had significantly lower DF-sIgE, MIF,
      ECP and eosinophil counts than those in a high temperature or high humidity
      climate. DF-sIgE correlated positively with MIF, ECP and eosinophil count in D.
      farinae-induced  asthma. CONCLUSIONS: Temperature and humidity influenced MIF,
      ECP, eosinophil count and DF-sIgE in D. farinae-induced asthma. Understanding
      this relationship may provide new strategies for asthma prevention and treatment.

PMID- 22613439
TI  - Advantages of single-stage surgical treatment with salter innominate osteotomy
      and Pemberton pericapsular osteotomy for developmental dysplasia of both hips.
AB  - OBJECTIVE: This study retrospectively compared the clinical and radiological
      outcomes of patients with bilateral developmental dysplasia of the hip who
      underwent either a single-stage operation (using a Salter innominate osteotomy
      for one hip and a Pemberton pericapsular osteotomy for  the other hip) or a two
      stage procedure comprising consecutive operations. METHODS: Extensive pre- and
      postoperative clinical, surgical and radiological examinations were undertaken.
      RESULTS: A total of 63 patients received the single-stage operation (group A),
      and 55 patients received consecutive  operations (group B). There were no
      significant between-group differences in acetabular index or centre-edge angle
      correction. Group A had significantly reduced anaesthetic exposure, duration of
      hospitalization, blood transfusion volume, antibiotic costs and hospitalization
      costs. Group A  also had a lower rate of surgical complications and avascular
      necrosis than group B. CONCLUSIONS: The single-stage surgical procedure was more
      economical and allowed more rapid recovery than two consecutive operations. The
      surgical and anaesthesia team must be highly proficient in order to  perform
      single-stage operations successfully.

PMID- 22613440
TI  - Comparison of bursting pressure after scleral tunnel incision sealed with sutures
      or an adherent ocular bandage in human globes.
AB  - OBJECTIVE: To evaluate the efficiency of a hydrogel adherent ocular bandage for
      sealing of scleral tunnel incisions in human eye globes. METHODS: A 4-mm scleral
      tunnel incision was made in each of 10 globes and bursting pressure was measured
      using the Seidel test to check for wound  leakage. Globes were sealed using
      either two interrupted 10-0 nylon sutures (n = 5) or an adherent ocular bandage
      in the form of polyethylene glycol hydrogel (n = 5). Bursting pressure was then
      measured for a second time. RESULTS: Bursting pressure was significantly higher 
      after wound sealing in both groups. There were no statistically significant
      differences in bursting pressure between the two groups before or after sealing.
      CONCLUSIONS: The adherent ocular bandage successfully protected the incision in
      ex vivo human globes immediately after surgery,  with a sealing efficiency
      comparable to two nylon sutures, suggesting that it is a safe and effective
      alternative to conventional suturing.

PMID- 22613441
TI  - In vitro differentiation of osteocytes and adipocytes from human placenta-derived
      cells.
AB  - OBJECTIVE: To investigate the capability of human placenta-derived adherent cells
      to differentiate into osteocytes and adipocytes. METHODS: Placenta-derived
      adherent cells were isolated by type IV collagenase digestion of a single freshly
      obtained human placenta and cultured under standard  conditions. Cell surface
      markers of adherent cells from passages 3 - 9 were analysed by flow cytometry.
      Osteocytic differentiation was induced with beta-glycerol phosphate, vitamin C
      and dexamethasone and confirmed by Alizarin red staining. Adipocytic
      differentiation was induced  with dexamethasone and insulin and confirmed by oil
      red O staining. RESULTS: Placenta-derived adherent cells were positive for high
      levels of CD44 and CD105 and very low levels of CD29 but were negative for CD34,
      CD45 and CD19. This pattern of cell surface markers is identical to human
      mesenchymal  stem cells. Alizarin red-positive cells were detected 10 days after
      the induction of osteocyte differentiation. Oil red O-positive cells were
      detected 7 days after the induction of adipocyte differentiation. CONCLUSIONS:
      Placenta-derived adherent cells can differentiate into either osteocytes  or
      adipocytes in vitro. The human placenta may provide an alternative source of
      mesenchymal stem cells for basic research and clinical use.

PMID- 22613442
TI  - Prognostic value of a single prehospital measurement of N-terminal pro-brain
      natriuretic peptide and troponin T after acute ischaemic stroke.
AB  - OBJECTIVE: Data regarding the value of prehospital measurement of N-terminal pro
      brain natriuretic peptide (NT-proBNP) and troponin T as prognostic indicators of
      in-hospital mortality are limited. This prospective pilot study aimed to
      determine the value of a single combined measurement  of NT-proBNP and troponin T
      for predicting in-hospital mortality in patients with acute ischaemic stroke in a
      prehospital emergency medicine centre. METHODS: Blood samples were collected in
      the prehospital setting and analysed for NT-proBNP and troponin T, using a
      portable device. Parameters  previously associated with stroke severity
      (including prognostic scoring systems) were recorded and assessed as independent
      predictors of in-hospital mortality. RESULTS: In logistic regression analysis,
      elevated troponin T (odds ratio [OR] 1.8 [95% CI 1.1, 8.4) and elevated NT-proBNP
      (OR 5.80  [95% CI 1.3, 22.7]) were significantly associated with poor outcome in
      patients with acute ischaemic stroke. Combined measurement of troponin T plus NT
      proBNP was most predictive of survival in stroke patients (93% sensitivity, 96%
      specificity, 80% negative predictive value, 98% positive predictive  value and
      92% area under the receiver operating curve). CONCLUSIONS: NT-proBNP and troponin
      T levels, measured during the prehospital phase of care after acute ischaemic
      stroke, are strong predictors of in-hospital mortality.

PMID- 22613443
TI  - Comparison of the predictive power of the LODS and APACHE II scoring systems in a
      neurological intensive care unit.
AB  - OBJECTIVE: A prospective study to compare the power of the Logistic Organ
      Dysfunction System (LODS) and the Acute Physiology and Chronic Health Evaluation
      II (APACHE II) scoring systems to predict survival, in patients admitted to the
      neurological intensive care unit (NICU). METHODS: Clinical data from 521
      consecutive NICU patients were collected during the first 24 h of admission and
      were used to compare the predictive power of both scoring systems. RESULTS: The
      observed mortality rate was 10.0% compared with predicted mortality rates of 7.2%
      and 4.8% according to LODS  and APACHE II, respectively. Both scoring systems had
      excellent discrimination but LODS had superior calibration. CONCLUSION: The LODS
      scoring system was more stable than the APACHE II scoring system in the NICU
      setting.

PMID- 22613444
TI  - Observational 6-month open-label study of Japanese type 2 diabetes patients
      switching from NPH insulin to insulin detemir in basal-bolus regimen: 23rd
      article of the Japan Diabetes Clinical Data Management Study Group (JDDM23).
AB  - OBJECTIVE: Glycaemic control is critical to prevent diabetic complications and
      mortality. This 6-month, open-label, observational study assessed the efficacy
      and safety of switching Japanese patients with type 2 diabetes from neutral
      protamine Hagedorn (NPH) insulin to insulin detemir. METHODS: Patients with type
      2 diabetes (n = 126) receiving basal-bolus insulin therapy with NPH insulin plus
      rapid-acting insulin analogues were recruited. NPH insulin was replaced with
      insulin detemir for 6 months. Glycosylated haemoglobin (HbA(1c)), fasting plasma
      glucose  (FPG), daily glucose levels and hypoglycaemia were monitored. Nocturnal
      quality of life was assessed by insulin therapy related quality of life at night
      questionnaire. RESULTS: HbA(1c), FPG and body weight were all significantly
      reduced after treatment with insulin detemir for 6 months,  without increasing
      severe hypoglycaemia. Insulin dose increased significantly over the same time.
      There were significant improvements in overall nocturnal quality of life, as well
      as well-being. CONCLUSIONS: Treatment with insulin detemir for 6 months resulted
      in substantial benefits, including  reduced HbA(1c), FPG and body weight, and
      improvements in nocturnal quality of life, without increasing hypoglycaemia.

PMID- 22613445
TI  - Ezetimibe reduces urinary albumin excretion in hypercholesterolaemic type 2
      diabetes patients with microalbuminuria.
AB  - OBJECTIVE: This study investigated the effects of ezetimibe, an inhibitor of
      intestinal cholesterol absorption, on early phase diabetic nephropathy. METHODS:
      A total of 32 hypercholesterolaemic type 2 diabetes patients with
      microalbuminuria, defined as a urinary albumin excretion (UAE)  30 but < 300 mg/g
      creatinine, were enrolled. Various clinical and laboratory parameters were
      determined at baseline and after 6 months of treatment with 10 mg/day ezetimibe.
      RESULTS: Ezetimibe treatment significantly decreased glycated haemoglobin
      (HbA(1c)), low-density lipoprotein-cholesterol  (LDL-C), triglycerides and UAE,
      and significantly increased high-density lipoprotein-cholesterol and albumin. It
      also decreased the serum level of monocyte chemoattractant protein-1 (MCP-1), but
      this difference was not statistically significant. Univariate analyses showed a
      correlation between  UAE and body mass index, systolic and diastolic blood
      pressures, HbA(1c), LDL-C, estimated glomerular filtration rate (inverse),
      creatinine and MCP-1. Since these parameters may be closely correlated with each
      other, multiple stepwise regression analysis was performed and demonstrated  that
      HbA(1c) and MCP-1 were independent determinants of UAE. CONCLUSIONS: Ezetimibe
      may be a promising therapeutic strategy for improving albumin excretion, partly
      through its anti-inflammatory properties, and for reducing LDL-C in
      hypercholesterolaemic type 2 diabetes patients with  microalbuminuria.

PMID- 22613446
TI  - Assessment of cardiac ultrasonography in predicting outcome in adult cardiac
      arrest.
AB  - OBJECTIVE: A prospective follow-up study to evaluate the ability of cardiac
      ultrasonography performed by emergency physicians to predict resuscitation
      outcome in adult cardiac arrest patients. METHODS: Ultrasonographic examination
      of the subxiphoid cardiac area was made immediately on presentation to the
      emergency department with pulseless cardiac arrest. Sonographic cardiac activity
      was defined as any detected motion within the heart including the atria,
      ventricles or valves. Successful resuscitation was defined as any of: return of
      spontaneous circulation for >= 20 min; return of breathing; palpable pulse;
      measurable blood pressure. RESULTS: The study enrolled 149 patients over an 18
      month period. The presence of sonographic cardiac activity at the beginning of
      resuscitation was significantly associated with a successful outcome (19/27
      [70.4%] versus 55/122 [45.1%] patients without cardiac activity at the beginning
      of resuscitation). CONCLUSIONS: Ultrasonographic detection of cardiac activity
      may be useful in determining prognosis during cardiac arrest. Further studies are
      needed to elucidate the predictive value of ultrasonography in cardiac arrest
      patients.

PMID- 22613447
TI  - Prevalence of the association of subacromial impingement with subcoracoid
      impingement and their clinical effects.
AB  - OBJECTIVES: A prospective study to determine how commonly chronic subacromial
      impingement is associated with subcoracoid impingement and to evaluate clinical
      outcome after arthroscopic subacromial decompression (ASD). METHODS: Subacromial
      and coracohumeral distances were evaluated in  patients with chronic shoulder
      pain before and after ASD, using magnetic resonance imaging and the University of
      California at Los Angeles (UCLA) shoulder scale and Constant-Murley shoulder
      assessment. RESULTS: A total of 40 patients were included in the study; patients
      were followed  up for a mean of 27.3 months. Before ASD, 14 (35%) patients with
      chronic subacromial impingement also had subcoracoid impingement. In these
      patients, the mean coracohumeral distance was 7.18 mm (range 5.00 - 11.00 mm).
      After ASD, no patient had subcoracoid impingement, and the mean coracohumeral 
      distance was significantly longer than pre-ASD, 12.85 mm (range 11.00 - 15.00
      mm). The Constant-Murley shoulder assessment and UCLA shoulder scale both showed
      improvement after ASD. CONCLUSIONS: Chronic subacromial impingement occurred
      together with subcoracoid impingement in 35%  of patients presenting with chronic
      shoulder pain. Following ASD, the coracohumeral distance increased with remission
      from pain.

PMID- 22613448
TI  - Malignant fibrous histiocytoma of the spermatic cord: case report and literature
      review.
AB  - This case study reports on a rare case of malignant fibrous histiocytoma arising
      in the right spermatic cord. An 80-year old male presented with a 2-week history
      of a right inguinal mass, with mild pain in the same region. Ultrasonography and
      computed tomography showed a mass arising from the right spermatic cord. A right
      radical orchiectomy was performed with wide dissection of the mass; the right
      testicle and epididymis were found not to be grossly involved. The patient had an
      uneventful postoperative course and recovered well. The patient and his family
      refused further adjuvant radiotherapy. There was no evidence of recurrence or
      metastasis during 20 months of regular follow-up. The diagnosis, histological
      classification, treatment and prognosis of this case are presented, together with
      a review of the literature.

PMID- 22613449
TI  - A rare midfoot injury pattern: navicular-cuneiform and calcaneal-cuboid fracture
      dislocation.

PMID- 22613450
TI  - The life-threatening complication of a vascular graft rupture early after a
      thoracic aortic replacement.
AB  - A 74-year old male presented with a dilatation of the thoracic aorta late after
      an acute aortic dissection. Computed tomography (CT) showed chronic dissecting
      aortic aneurysms just below the distal aortic arch. The total descending thoracic
      aorta was surgically replaced. Four weeks later, a massive bloody effusion
      developed in the right thorax and a subsequent CT scan revealed an extravasation
      of the contrast material out of the vascular prosthesis. Emergency surgery
      disclosed bleeding from a small vascular graft rupture and a successful repair
      was performed.

PMID- 22613451
TI  - Cognitive functioning in euthymic recurrently depressed patients: relationship
      with future relapses and prior course of disease.
AB  - BACKGROUND: Cognitive impairment seems to persist during the euthymic phase of
      recurrent depression but its relationship with future relapses as with prior
      course of the disease has to be elucidated. The purpose of this study is to
      investigate the presence and prognostic value of cognitive dysfunctions for
      relapse in high risk euthymic patients and to identify relevant associations
      between cognitive functioning and prior course of illness. METHODS: Standardized
      neuropsychological tests of mental speed, memory and executive functioning were
      assessed in 137 remitted patients and compared with clinically used published
      normative data. Previous episodes and relapses within 24 months were measured
      using the Structured Clinical Interview for DSM-IV. RESULTS: Cognitive
      performance was significantly impaired on 12 of the 14 variables indicating
      deficits in the domain of speed of information processing and memory. With Cox
      regression no significant neuropsychological predictors for relapse or recurrence
      were identified. Furthermore, Pearson correlations between neuropsychological
      test scores and number of previous episodes, residual depressive symptoms and
      duration of remission were non-significant. Later age of onset was correlated
      with a slower speed of information processing and lower verbal memory
      performance. LIMITATIONS: Published test reference data were used but no healthy
      control group. CONCLUSION: Presence of mild cognitive impairment in remitted
      patients was demonstrated but did not predict future relapses nor was it related
      with prior course of disease except for age of onset. Though, mild cognitive
      impairment after remission might have an impact on the quality of life, adding
      techniques from cognitive rehabilitation might prove to be a treatment option.

PMID- 22613452
TI  - Expandable proximal femoral nails versus 95 degrees  dynamic condylar screw
      plates for the treatment of reverse oblique intertrochanteric fractures.
AB  - The treatment of a simple (AO/OTA classification 31A3.1) reverse oblique
      intertrochanteric hip fracture is a challenge for the orthopaedic surgeon. The
      surgical options include the use of side plates with various angled leg screws or
      intramedullary devices. The purpose of this study was to retrospectively assess
      our results of treating reverse oblique fracture with an expendable proximal
      femoral nail (EPFN) or with a dynamic condylar screw-plate (DCS: 95 degrees )
      between January 2006 and July 2009. Thirty-three patients (6 males and 27
      females, mean age 78 years) met the study inclusion criteria and comprised the
      two study groups: 19 had been treated by EPFNs and 14 had received DCSs. They
      were followed for a mean of 28 months (range 6-47). Eight patients (5 EPFN and 3
      DCS) died during the follow-up period from causes not related to the operation.
      Two ESPN patients and 5 DCS patients had malunions. Functional outcome scores
      showed better results in the EPFN group, but the difference was statistically
      significant only for the sitting subcategory (p=0.04). Based on our results and
      experience, we propose that the EPFN is at least as good as the DCS for treating
      reverse oblique fractures of the femur.

PMID- 22613453
TI  - Lower limb injuries caused by improvised explosive devices: proposed 'Bastion
      classification' and prospective validation.
AB  - BACKGROUND: Complex lower limb injury caused by improvised explosive devices
      (IEDs) has become the signature wounding pattern of the conflict in Afghanistan.
      Current classifications neither describe this injury pattern well, nor correlate
      with management. There is need for a new classification, to aid communication
      between clinicians, and help evaluate interventions and outcomes. We propose such
      a classification, and present the results of an initial prospective evaluation.
      PATIENTS AND METHODS: The classification was developed by a panel of military
      surgeons whilst deployed to Camp Bastion, Afghanistan. Injuries were divided into
      five classes, by anatomic level. Segmental injuries were recognised as a distinct
      entity. Associated injuries to the intraperitoneal abdomen, genitalia and
      perineum, pelvic ring, and upper limbs, which impact on clinical management and
      resources, were also accounted for. RESULTS: Between 1 November 2010 and 20
      February 2011, 179 IED-related lower limb injuries in 103 consecutive casualties
      were classified, and their subsequent vascular and musculoskeletal treatment
      recorded. 69% of the injuries were traumatic amputations, and the remainder
      segmental injuries. 49% of casualties suffered bilateral lower limb amputation.
      The most common injury was class 3 (involving proximal lower leg or thigh,
      permitting effective above-knee tourniquet application, 49%), but more proximal
      patterns (class 4 or 5, preventing effective tourniquet application) accounted
      for 18% of injuries. Eleven casualties had associated intraperitoneal abdominal
      injuries, 41 suffered genital or perineal injuries, 9 had pelvic ring fractures,
      and 66 had upper limb injuries. The classification was easy to apply and
      correlated with management. CONCLUSIONS: The 'Bastion classification' is a
      pragmatic yet clinically relevant injury categorisation, which describes current
      injury patterns well, and should facilitate communication between clinicians, and
      the evaluation of interventions and outcomes. The validation cohort confirms that
      the injury burden from IEDs in the Helmand Province of Afghanistan remains high,
      with most casualties sustaining amputation through or above the knee. The rates
      of associated injury to the abdomen, perineum, pelvis and upper limbs are high.
      These findings have important implications for the training of military surgeons,
      staffing and resourcing of medical treatment facilities, to ensure an adequate
      skill mix to manage these complex and challenging injuries.

PMID- 22613454
TI  - Comparative structural modeling of a monothiol GRX from chickpea: insight in iron
      sulfur cluster assembly.
AB  - Glutaredoxins (GRXs) are small, ubiquitous, multifunctional, heat-stable and
      glutathione-dependent thiol-disulphide oxidoreductases, classified under
      thioredoxin-fold superfamily. In the green lineage, GRXs constitute a complex
      family of proteins. Based on their active site, GRXs are classified into two
      subfamilies: dithiol and monothiol. Monothiol GRXs contain 'CGFS' as a redox
      active motif and assist in maintaining redox state and iron homeostasis within
      the cell. Using RACE strategy, a full length cDNA of chickpea (Cicer arietinum)
      glutaredoxin 3 (CarGRX3) was cloned and sequenced. The cDNA contains open reading
      frame of 537 bp encoding 178 amino acids and exhibits features of other known
      'CGFS' type GRXs. Based on the multiple sequence alignment among CarGRX3 and
      monothiol GRXs of other photosynthetic organisms, the characteristic motif
      (KGX4PXCGFSX([29/30/32])KX4WPTXPQX4GX3GGXDI) with 18 invariant residues was
      observed. The proposed structure of CarGRX3 was compared with structurally
      resolved monothiol GRXs of other organisms. The CarGRX3 and nearest Arabidopsis
      homolog (AtGRXcp) shares 76% sequence identity which was reflected by their 3D
      structure conservation. The structure of chickpea monothiol GRX (CarGRX3)
      coordinates glutathione ligated [2Fe-2S] cluster in a homodimeric form,
      highlighting the structural basis for iron-sulfur cluster (ISC) assembly and
      delivery to acceptor proteins. The present study on CarGRX3 model highlighted the
      utility of the theoretical approaches to understand complex biological phenomena
      such as glutathione docking and incorporation of GSH-ligated [2Fe-2S] cluster.

PMID- 22613455
TI  - Spatial memory and the avian hippocampus: research in zebra finches.
AB  - The aim of the present review is to show that spatial learning and memory is not
      a specialty of just a few avian species, and to describe the role of the avian
      hippocampus in spatial learning, memory and orientation. Based on our own
      research in zebra finches, we try to give an (not complete and probably biased)
      overview of this topic, and we also discuss the question of functional
      equivalence of hippocampus in birds and in mammals in that we question how far
      theories developed for mammalian hippocampus can also be applied to the avian
      hippocampal formation. 

PMID- 22613456
TI  - The archaellum: an old motility structure with a new name.
AB  - Motility structures, called flagella, have been described in all three domains of
      life: Bacteria, Archaea and Eukarya. These structures are well studied in both
      Bacteria and Eukarya. However, already in eukaryotes there exists some confusion
      as to whether these structures should actually be called cilia. With increased
      studies conducted on organisms of the third domain of life, the Archaea, it has
      become clear that the archaeal flagellum only functionally appears similar to the
      bacterial flagellum, whereas it structurally resembles a bacterial type IV pilus.
      To resolve confusion due to unclear nomenclature, we propose renaming the
      archaeal flagellum as the 'archaellum'. This will make clear that the archaellum
      and the bacterial flagellum are two distinct structures that happen to both be
      used to enable microorganisms to swim.

PMID- 22613457
TI  - Physiological regulatory networks: ecological roles and evolutionary constraints.
AB  - Ecological and evolutionary physiology has traditionally focused on one aspect of
      physiology at a time. Here, we discuss the implications of considering
      physiological regulatory networks (PRNs) as integrated wholes, a perspective that
      reveals novel roles for physiology in organismal ecology and evolution. For
      example, evolutionary response to changes in resource abundance might be
      constrained by the role of dietary micronutrients in immune response regulation,
      given a particular pathogen environment. Because many physiological components
      impact more than one process, organismal homeostasis is maintained, individual
      fitness is determined and evolutionary change is constrained (or facilitated) by
      interactions within PRNs. We discuss how PRN structure and its system-level
      properties could determine both individual performance and patterns of
      physiological evolution.

PMID- 22613458
TI  - Variability in delivery of care and echocardiogram surveillance of Kawasaki
      disease.
AB  - OBJECTIVE: The objective of this study is to characterize variability in the
      acute management of Kawasaki disease and compliance of echocardiogram
      surveillance with published American Heart Association recommendations. DESIGN:
      Retrospective review. SETTING: Tertiary care children's hospital. PATIENTS: All
      patients discharged from our institution with Kawasaki Disease between 1999 and
      2007 were identified. Patients meeting any of the following were excluded:
      presence of a comorbidity that necessitated echocardiogram follow-up independent
      of Kawasaki disease diagnosis, previous history of Kawasaki disease, or magnetic
      resonance imaging of the coronary arteries performed in place of
      echocardiography. Preexisting or comorbid conditions resulting in study exclusion
      included structural heart disease, arrhythmia, and concomitant severe multiorgan
      disease at presentation (e.g., sepsis). OUTCOME MEASURES: The time course of
      echocardiogram surveillance among those with a normal echocardiogram at diagnosis
      was evaluated for compliance with published American Heart Association
      recommendations. Coronary artery involvement at presentation was characterized
      using standardized values. Additional characterization of national care practices
      for children with Kawasaki disease was obtained via distribution of an internet
      based survey to pediatric hospitalists. RESULTS: Overall, only 11 (4%) of 302
      patients with a normal study at diagnosis received a total of three studies at
      recommended intervals. Using standardized values for coronary artery dimensions
      in place of Japanese Ministry of Health aneurysm criteria, 59 (13%) of patients
      with Kawasaki disease experienced coronary artery involvement at diagnosis. The
      majority of the early coronary artery abnormalities detected in these patients
      using standardized definitions persisted on short-term follow-up. Pediatric
      hospitalist survey results revealed significant interinstitutional variability in
      the management of these patients. CONCLUSIONS: Lack of optimal surveillance after
      a diagnosis of Kawasaki disease may result in the underdiagnosis of coronary
      artery pathology or other complications. Considerable variability in surveillance
      and acute management exists, and additional research is needed to determine
      optimal screening and care delivery models for this population.

PMID- 22613459
TI  - Case report: lymphoepithelial-like carcinoma of the lung--a chronic disease?
AB  - This is a case of metastatic lung cancer of the lymphoepithelial-like carcinoma
      (LELC) variant who first presented with symptomatic brain metastasis. The patient
      underwent local and systemic treatment for metastatic disease with good clinical
      outcome. The patient was disease free for four years then she had primary lung
      recurrence which was surgically resected. She underwent a second course of
      chemotherapy with saw her through another two years of disease free period. A
      recurrence of the cancer was detected intra-abdominally on the seventh year of
      diagnosis. This was treated again with surgical resection and another course of
      chemotherapy.

PMID- 22613461
TI  - Intra-individual variation of the cuff-leak test as a predictor of post
      extubation stridor.
AB  - BACKGROUND: This was an evaluation of intra-individual variation of the cuff-leak
      test (DeltaCLT) immediately post-intubation and pre-extubation, as a predictor of
      post-extubation stridor. METHODS: Prospective, clinical investigation in the ICU
      of a non-university hospital. CLTs were performed immediately after intubation
      (T0) and before extubation (T1) to evaluate the differences in cuff leak
      (DeltaCLT = CL(T1) - CL(T0)). RESULTS: We included 104 mechanically ventilated
      subjects in the study over a 12-month period. The incidence of post-extubation
      stridor was 6.7%. Stridor was more common in females of short stature. DeltaCLT
      was considered as significant when CL(T1) - CL(T0) was negative. The sensitivity
      and the specificity of the test were 86% and 48%, respectively. When we tested
      the pre-extubation CLT alone with a threshold of 130 mL as a predictor of post
      extubation stridor, the sensitivity and the specificity of the test were 86% and
      76%, respectively. CONCLUSIONS: The intra-individual variation of CLT immediately
      post-intubation and pre-extubation does not improve the accuracy of a standard
      pre-extubation CLT to predict post-extubation stridor. Moreover, the standard pre
      extubation CLT did not appear in our study to be an ideal test to detect post
      extubation stridor. Larger studies should be performed before generalizing these
      preliminary results.

PMID- 22613462
TI  - Pyonephrosis and urosepsis in a 41-year old patient with spina bifida: Case
      report of a preventable death.
AB  - BACKGROUND: Urological complications are the major cause of ill health in
      patients with spina bifida. Urinary sepsis accounted for the majority of
      admissions in patients with spina bifida. As the patient grows older, changes
      occur in the adult bladder, leading to increases in storage pressure and
      consequent risk of deterioration of renal function, which may occur insidiously.
      CASE PRESENTATION: A 34-year-old male spinal bifida patient had been managing
      neuropathic bladder by penile sheath. Intravenous urography revealed normal
      kidneys. This patient was advised intermittent catheterisations. But self
      catheterisation was not possible because of long, overhanging prepuce and marked
      spinal curvature. This patient developed repeated urine infections. Five years
      later, ultrasound examination of urinary tract revealed hydronephrotic right
      kidney with echogenic debris within the collecting system. There was no evidence
      of dilatation of the ureter near the vesicoureteric junction. The left kidney
      appeared normal. There was no evidence of calculus disease seen in either kidney.
      Indwelling urethral catheter drainage was established.Two years later, MAG-3
      renogram revealed normal uptake and excretion by left kidney. The right kidney
      showed little functioning tissue. Following a routine change of urethral catheter
      this patient became unwell. Ultrasound examination revealed hydronephrotic right
      kidney containing thick hyper-echoic internal septations and debris in the right
      renal pelvis suspicious of pyonephrosis. Under both ultrasound and fluoroscopic
      guidance, an 8 French pig tail catheter was inserted into the right renal
      collecting system. 150 ml of turbid urine was aspirated immediately. This patient
      developed large left pleural effusion, collapse/consolidation of the left lower
      lobe, a large fluid collection in the abdomen extending into the pelvis and
      expired twenty days later because of sepsis and respiratory failure. CONCLUSION:
      Although penile sheath drainage may be convenient for a spina bifida patient and
      the carers, hydronephrosis can occur insidiously. With recurrent urine
      infections, hydronephrotic kidney can become pyonephrosis, which is life
      threatening. Therefore, every effort should be made to carry out intermittent
      catheterisations along with antimuscarinic drug therapy.

PMID- 22613460
TI  - The cholangiocyte marker, BD. 1, forms a stable complex with CLIP170 and shares
      an identity with eIF3a, a multifunctional subunit of the eIF3 initiation complex.
AB  - We have previously described the generation of a monoclonal antibody recognizing
      a novel cholangiocyte marker, designated BD.1, that is expressed by fetal and
      adult rat cholangiocytes but not hepatocytes or the hepatic progenitor cells
      known as oval cells. In the present report, we have undertaken a comprehensive
      examination of BD.1 expressed by long-term cultures of bile duct epithelial cells
      (BDEC) and prostate epithelial cells (PEC). We show that with continued passage,
      the levels of BD.1 expressed by BDEC and PEC drop significantly, a decrease that
      is temporally associated with transition from a diploid to an aneuploid
      karyotype. Cell cycle analysis revealed cell cycle dependent expression of BD.1
      characterized by decreased BD.1 levels within the first 10 h after release from
      serum starvation followed by reacquisition as cells entered S phase. MAb BD.1
      recognized a 170 kDa protein in Western blots and showed strong reactivity with a
      170 kDa band in blots prepared from phosphoproteins isolated by metal affinity
      chromatography. Analysis by mass spectrometry of tryptic peptides generated from
      BD.1 purified by continuous elution electrophoresis identified the plus end
      microtubule-binding protein, CLIP170, in the fraction reactive with MAb BD.1.
      Double immunofluorescence with MAb BD.1 and a MAb specific for CLIP170 showed
      that both were reactive with intrahepatic bile ducts. However, overexpression or
      siRNA knockdown of CLIP170 in 293T cells did not significantly alter BD.1 levels,
      indicating that CLIP170 and BD.1 were distinct, co-migrating proteins.
      Immunoprecipitation analysis with MAb BD.1 and anti-CLIP170 antibodies showed
      that under microtubule depolymerizing conditions the two proteins could be co
      precipitated with both antibodies, leading us to conclude they were capable of
      forming stable complexes. Two different protocols were devised to enrich for the
      CLIP170 binding protein recognized by MAb BD.1. Analysis of tryptic peptides by
      LC-ESI-MS/MS identified BD.1 as eIF3a, the largest subunit of the elongation
      initiation factor 3 (eIF3) complex. This identity was confirmed by the
      simultaneous knockdown of both BD.1 and eIF3a by eIF3a-specific siRNAs and by the
      strong reactivity of MAb BD.1 with the 170 kDa protein immunoprecipitated with
      the anti-eIF3a antibody, 5H10. Based on these findings, we concluded that the
      BD.1 antigen was identical to eIF3a, a multifunctional subunit of the eIf3
      complex shown here to associate with microtubules through its interactions with
      CLIP170.

PMID- 22613463
TI  - 239Pu and 240Pu inventories and 240Pu/239Pu atom ratios in the equatorial Pacific
      Ocean water column.
AB  - The (239+240)Pu concentrations and (240)Pu/(239)Pu atom ratios were determined by
      alpha spectrometry and inductively coupled plasma mass spectrometry for seawater
      samples from two stations, one at the equator and the other in the equatorial
      South Pacific. To better understand the fate of Pu isotopes, this study dealt
      with the contribution of the close-in fallout Pu from the Pacific Proving Grounds
      (PPG) in water columns of the Pacific Ocean. The (239)Pu, (240)Pu and (239+240)Pu
      inventories over the depth interval 0-3000 m at the equator station were 10.4,
      8.9 and 19.3 Bq m(-2), respectively. Further, no noticeable difference was
      observed in (239)Pu, (240)Pu and (239+240)Pu inventories over the depth interval
      0-3000 m between the two stations. The total (239+240)Pu inventories were
      significantly higher than the expected cumulative deposition density of global
      fallout. Water column (239+240)Pu inventories measured in this study were lower
      than those reported for comparable stations in the Geochemical Ocean Sections
      Study, indicating that these inventories have been decreasing at average rates of
      0.89 +/- 0.07 and 0.16 +/- 0.07 Bq m(-2)yr(-1) at the equator and equatorial
      South Pacific stations, respectively, from 1973 to 1990. The obtained
      (240)Pu/(239)Pu atom ratios were higher than the mean global fallout ratio of
      0.18. These high atom ratios proved the existence of close-in tropospheric
      fallout Pu from the PPG in the Marshall Islands. The (239+240)Pu inventories
      originating from the close-in fallout in the entire water column were estimated
      to be 11.1 Bq m(-2) at the equator station and 7.1 Bq m(-2) at the equatorial
      South Pacific Ocean station, and the relative percentages of close-in fallout Pu
      were 40% at the former and 34% at the latter. A significant amount of close-in
      fallout Pu originating from the PPG has been transported to deep layers below the
      1000 m depth in the equatorial Pacific Ocean.

PMID- 22613464
TI  - Comparison of elemental contents in earthworm cast and soil from a mercury
      contaminated site (Idrija area, Slovenia).
AB  - The aim of this paper was to test the new sampling media-earthworm casts in a
      highly contaminated area. The investigation was carried out at the ancient Hg ore
      roasting site Psenk in the surroundings of Idrija, where extremely high Hg
      contents in soils and SOM were determined in previous investigations. 32
      earthworm cast samples were collected in the research grid 30 * 30 m in order to
      compare the Hg contents and spatial distribution in earthworm casts to the values
      and distributions in SOM and soil (0-15 cm). Extremely elevated Hg concentrations
      were determined in earthworm casts from the studied area ranging from 5.4 to 4330
      mg/kg with the median of 31 mg/kg. The Hg values in casts are somewhat lower than
      in soil (6.3-8600 mg/kg) and slightly higher compared to soil organic matter
      (SOM) (1.5-4200 mg/kg). Strong correlation (r2=0.75) between Hg contents in casts
      and soil was found, while correlation between casts and SOM was positive but
      weaker (r2=0.35). Spatial distribution of Hg in earthworm casts show the highest
      concentrations in the central part of investigated area, similar to the
      distribution in soil. Hg contents rapidly decrease from the center toward the
      margins of the studied area, where they reach values of less than 50mg/kg. It was
      shown that Hg contents and dispersion in casts are comparable to those in soil,
      which indicates that at investigated area soil contamination is strongly
      reflected in contamination of earthworm casts.

PMID- 22613466
TI  - Neuropsychological characteristics associated with olfactory hallucinations in
      schizophrenia.
AB  - Olfactory hallucinations (OHs) are present in a significant minority of people
      with schizophrenia, yet these symptoms are under-researched and poorly
      understood. This study aimed to identify the neuropsychological impairments that
      associate with OHs in schizophrenia. Patients with schizophrenia or
      schizoaffective disorder were classified into an OH group and a group with
      auditory-verbal hallucinations (AVHs) and no lifetime history of OHs. Patients
      were age- and gender-matched to a healthy control group. All participants were
      assessed using: a test of odor identification; decision-making and socio
      emotional tests of orbitofrontal cortex (OFC) and amygdala function; and a
      battery of standardized executive tests. Patients, as a whole, performed more
      poorly than controls on the tests of odor identification, emotion processing and
      executive function, consistent with previous research. Only two tests of OFC
      functioning: the Object Alternation Task, taken from Oscar-Berman and Zola
      Morgan's (1980a, 1980b) Comparative Neuropsychological Tasks, and a test of "faux
      pas" understanding discriminated between the OH and AVH patients. Findings
      provide the first preliminary support for OH-specific neuropsychological
      impairments associated with OFC dysfunction in schizophrenia. (JINS, 2012, 18, 1
      10).

PMID- 22613465
TI  - Chemical composition and minerals in pyrite ash of an abandoned sulphuric acid
      production plant.
AB  - The extraction of sulphur produces a hematite-rich waste, known as roasted pyrite
      ash, which contains significant amounts of environmentally sensitive elements in
      variable concentrations and modes of occurrence. Whilst the mineralogy of roasted
      pyrite ash associated with iron or copper mining has been studied, as this is the
      main source of sulphur worldwide, the mineralogy, and more importantly, the
      characterization of submicron, ultrafine and nanoparticles, in coal-derived
      roasted pyrite ash remain to be resolved. In this work we provide essential data
      on the chemical composition and nanomineralogical assemblage of roasted pyrite
      ash. XRD, HR-TEM and FE-SEM were used to identify a large variety of minerals of
      anthropogenic origin. These phases result from highly complex chemical reactions
      occurring during the processing of coal pyrite of southern Brazil for sulphur
      extraction and further manufacture of sulphuric acid. Iron-rich submicron,
      ultrafine and nanoparticles within the ash may contain high proportions of toxic
      elements such as As, Se, U, among others. A number of elements, such as As, Cr,
      Cu, Co, La, Mn, Ni, Pb, Sb, Se, Sr, Ti, Zn, and Zr, were found to be present in
      individual nanoparticles and submicron, ultrafine and nanominerals (e.g. oxides,
      sulphates, clays) in concentrations of up to 5%. The study of nanominerals in
      roasted pyrite ash from coal rejects is important to develop an understanding on
      the nature of this by-product, and to assess the interaction between emitted
      nanominerals, ultra-fine particles, and atmospheric gases, rain or body fluids,
      and thus to evaluate the environmental and health impacts of pyrite ash
      materials.

PMID- 22613467
TI  - [Transzygomatic pterional approach. Part 2: Surgical experience in the management
      of skull base pathology].
AB  - OBJECTIVES: To present our experience with the transzygomatic pterional approach
      in the treatment of neurosurgical pathology of the base of the skull located in
      the middle cranial fossa and surrounding areas. METHOD: A retrospective study of
      pathological findings, surgical outcomes and complications in a series of 31
      cases operated on between 2009 and 2011 using a transzygomatic pterional
      approach. RESULTS: The lesions involved the sphenoid wing (25.9%), several
      regions due to invasive growth pattern (19.5%), the temporal lobe (16.1%) and
      cavernous sinus (12.9%). The others were located in the floor of the middle
      fossa, Meckel's cave, incisural space, cisterns and infratemporal region. The
      pathological nature of the lesions was: benign meningioma (42%), temporal lobe
      tumour (19.5%), vascular disease (12.9%), inflammatory lesions (6.4%), atypical
      meningioma (6.4%), epidermoid cyst (6.4%), neurinoma (3.2%) and poorly
      differentiated infratemporal carcinoma (3.2%). The approach was usually combined
      extra-intradural (58.1%) and, less frequently, just extradural (16.1%) or
      intradural (25.8%). Approach-related complications were minor: haematomas in the
      wound not requiring treatment (67.8%), superior transient facial paresis (9.7%),
      transient temporomandibular joint dysfunction (12.9%) and atrophy of the temporal
      muscle (16.2%). There were no hardware-related complications or cosmetic issues
      related to the osteotomy and posterior osteosynthesis of the zygomatic arch.
      CONCLUSIONS: The pterional approach combined with osteotomy of the zygomatic arch
      allows mobilising the temporalis muscle away from the temporal fossa,
      consequently exposing its entire surface to complete the temporal craniotomy up
      to the middle fossa; it helps to access and treat pathology in this region or it
      can be used as a corridor to approach surrounding areas.

PMID- 22613468
TI  - Yellow fever vaccination centers: concurrent vaccinations and updates on mosquito
      biology.
AB  - Mandatory visits to immunization centers that offer pre-travel Yellow fever
      vaccine to prospective travelers would be useful for briefing the basics of the
      biology of the mosquito responsible for Yellow fever spread. Pre- travel
      knowledge on the day-time rather the nocturnal biting habit of the mosquitoes of
      Aedes species would prevent from bites of the mosquitoes responsible for the
      spread of viruses causing Yellow fever, dengue or Chikungunya infection.

PMID- 22613469
TI  - Modeling SDF-1-induced mobilization in leukemia cell lines.
AB  - The stromal cell-derived factor 1 (SDF-1) is essential for circulation, homing,
      and retention of hematopoietic stem cells in the bone marrow. Present evidence
      indicates that this factor might play an important role in leukemia cells as
      well. The aim of this study is to present a model of SDF-1-induced mobilization
      using leukemia cell lines. CXCR4 expression was compared in Kasumi-1, Jurkat, HL
      60, KG-1a, and K562 cells by flow cytometry and Western blot. Migration was
      analyzed with Transwell assays, and adhesive cell-cell interaction was quantified
      with a standardized adhesion assay and flow cytometry. CXCR4 was expressed by all
      leukemic cell lines analyzed, although surface expression of this receptor was
      found in Kasumi-1 and Jurkat cells only. Correspondingly, SDF-1alpha effects on
      migration and cell-cell adhesion were observed in Kasumi-1 and Jurkat cells only,
      and this could be blocked by AMD3100 in a reversible manner. We have provided
      evidence that SDF-1alpha acts as a chemotactic and chemokinetic agent. In
      addition, surface expression of integrin-beta2, activated leukocyte cell adhesion
      molecule and N-cadherin decreased after stimulation with SDF-1alpha. SDF-1alpha
      affects cell-cell adhesion and migration only in leukemia cells on which the
      CXCR4 receptor is present on the surface. An SDF-1 gradient is not necessarily
      required to induce migration, as chemokinesis can also occur. Upon stimulation
      with SDF-1, CXCR4 promotes modifications on the surface pattern of adhesion
      molecules, which have an influence on adhesion and migration.

PMID- 22613470
TI  - A NUP98-HOXD13 leukemic fusion gene leads to impaired class switch recombination
      and antibody production.
AB  - Myelodysplastic syndrome is a clonal process characterized by ineffective
      hematopoiesis and progression to acute leukemia. Although many myelodysplastic
      syndrome and leukemic patients have compromised immunity, the role of underlying
      mutations in regulating immune function is poorly understood. Recent studies show
      that NUP98-HOXD13 (NHD13) fusion gene results in myelodysplastic syndrome and
      impairs lymphocyte differentiation in transgenic mice. In our studies, we sought
      to elucidate the mechanism by which NHD13 affects B-lymphocyte development and
      function. Based on our preliminary findings that transgenic mice had increased
      levels of IgM and reduced IgG1 and IgE, we hypothesized that the fusion gene
      might impair class switch recombination (CSR). Mice were immunologically
      challenged with dinitrophenol. NHD13 mice showed a marked reduction in B
      lymphocyte differentiation in their bone marrow and spleen following
      dinitrophenol stimulation and had reduced production of dinitrophenol-specific
      antibodies. Spleen follicles from these mice were small and hypocellular,
      indicating failure of clonal expansion. When isolated NHD13 B lymphocytes were
      stimulated in vitro using Escherichia coli lipopolysaccharide or
      lipopolysaccharide + interleukin-4, they failed to undergo sufficient CSR and
      proliferation. Taken together, our findings show that expression of NUP98-HOXD13
      impairs CSR and reduces the antibody-mediated immune response, in addition to its
      role in leukemia. Further delineation of the NUP98-HOXD13 transgene may reveal
      novel pathways involved in CSR.

PMID- 22613472
TI  - [Reasons for abolishing the Massage Department of the Imperial Academy of
      Medicine in the 5(th) year of Longqing Period of the Ming Dynasty].
AB  - In the 5th year of the Longqing Period (1571) of the Ming Dynasty, with the
      abolishment of the Massage and Zhuyou Departments (the latter with a primitive
      witch doctor, who was dominant in administering incantations, prayers, fortune
      telling and medicine), the number of departments of the Imperial Academy of
      Medicine was reduced from thirteen to eleven. In the Jiaqing Period, Taoists
      occupied some positions in the Imperial Academy of Medicine. Some of them became
      imperial doctors or even the president, which resulted in Emperor Jiaqing
      pursuing immortality and neglecting duty on national affairs for more than 20
      years. The abolishment of the Massage Department was associated with the official
      system of reform developed by Emperor Longqing and the prime minister, Gao Gong.
      Against the background of official reform, they also advanced bold reform in the
      two departments which Taoists occupied.

PMID- 22613471
TI  - IGF signaling contributes to malignant transformation of hematopoietic
      progenitors by the MLL-AF9 oncoprotein.
AB  - Malignant transformation of normal hematopoietic progenitors is a multistep
      process that likely requires interaction between collaborating oncogenic signals
      at critical junctures. For instance, the MLL-AF9 fusion oncogene is thought to
      contribute to myeloid leukemogenesis by driving a hematopoietic stem cell-like
      "self-renewal" gene expression signature in committed myeloid progenitors. In
      addition, insulin-like growth factor (IGF) signaling has been implicated in self
      renewal/pluripotency in hematopoietic and embryonic stem cell contexts and
      supports cell growth/survival by activation of downstream pathways, including
      phosphatidylinositol 3-kinase/Akt and Ras/Raf/extracellular signal-regulated
      kinase. We hypothesized that IGF signaling could be an important contributor in
      the process of cellular transformation and/or clonal propagation. Utilizing an
      MLL-AF9 mouse bone marrow transplantation model of acute myelogenous leukemia, we
      discovered that committed myeloid progenitor cells with genetically reduced
      levels of IGF1R were less susceptible to leukemogenic transformation due, at
      least in part, to a cell-autonomous defect in clonogenic activity. Rather
      unexpectedly, genetic deletion of IGF1R by inducible Cre recombinase had no
      effect on growth/survival of established leukemia cells. These findings suggest
      that IGF1R signaling contributes to transformation of normal myeloid progenitor
      cells, but is not required for propagation of the leukemic clone once it has
      become established. We also show that treatment of mouse MLL-AF9 acute
      myelogenous leukemia cells with BMS-536924, an IGF1R/insulin receptor-selective
      tyrosine kinase inhibitor, blocked cell growth, suggesting its efficacy in this
      model may be due to inhibition of insulin receptor and/or related tyrosine
      kinases, and raising the possibility that similar IGF1R inhibitors in clinical
      development may be acting through alternate/related pathways.

PMID- 22613473
TI  - [Differences of concept and entity of xiao-named herb between Shennong's Herbal
      Classic and Song-edition Treatise on Febrile Disease and Golden Chamber].
AB  - There are significant differences of the XIAO-named herb between Shennong's
      Herbal Classic and the Song-edition Treatise on Febrile Disease and Synopsis of
      the Golden Chamber. The reasons are: (1) With the development of history,
      differentiation of herb category and effect kept changing from the Han Dynasty to
      the Song Dynasty, which led to the differences in concept and entity of herbs in
      different periods. (2) Lin Yi of the Song Dynasty may have redefined some herb's
      names according to the current situation when he revised Zhang Zhongjing's works.

PMID- 22613474
TI  - [Analysis of Antisepsis techniques of the Ming-period corpse excavated in
      Taizhou].
AB  - Four well-preserved Ming-period corpses were excavated singly from 1980 to 2011.
      With the same condition of preservation, those corpses were distributed within a
      range of less than 1 square kilometer. Analysis of the burial situation concluded
      that a long period before burial caused the body to become dehydrated and
      mummified, which was the basic preservation condition. After the burial in a
      confined space with constant temperature, humidity and antibacterial conditions,
      the body could be preserved as a wet corpse (corpse like a fresh body).

PMID- 22613476
TI  - [Medical exchanges between China and Vietnam during the Song, Jin and Yuan
      Periods].
AB  - There were many medical exchanges between China and Vietnam during the Song, Jin
      and Yuan Periods. For example, in the Li Period, Vietnam established the Imperial
      Medical Department according to medical administration in China and to the Chen
      Period, the name was changed to Imperial Academy of Medicine. Through tribute and
      trade, many medicines circulated between the two countries. Many medicines from
      Vietnam, especially the spices and perfumes, could be found in prescriptions in
      China during those periods. Except for herb exchange, Chinese doctors also
      brought TCM theory to Vietnam and they offered medical attention for people and
      the Emperor. At the same time, Vietnamese doctors also had treated disease for a
      Chinese Empress in the Song Dynasty. In the area of the Sino-Vietnam border,
      people are used to chewing betel, which has been recorded in Chinese medical
      books.

PMID- 22613477
TI  - [History of cancer registration in china].
AB  - The first cancer registry office was established in 1959 in China. In 1969, most
      provinces, autonomous regions and independently administered municipal districts
      had their own cancer prevention offices. In the 1970s, many cancer high incidence
      areas began their work on cancer registration. Thirty-eight cancer registry
      offices had been set up by the 1980s. In 1990 the China Cancer Registration
      Collaboration Regulations were made and in 2003, the Plan of Cancer Prevention
      and Control was issued by the Ministry of health of China. Cancer registration
      was emphasized as the main feature of cancer prevention and control. In 2004, the
      China Cancer Registration Handbook was published and at the same time, the China
      Institute of Health Information and the Cancer Registration and Monitoring Board
      were established and regulations of the board had been passed. Until now there
      are 195 cancer registry offices in China (80 in cities and 113 in rural areas)
      covering about 190 million people which accounts for 13% of the Chinese
      population.

PMID- 22613475
TI  - [Study of the medical macrofungal literature in Hui Hui Yao Fang].
AB  - Words on medical macrofungi appeared over one hundred times in Hui Hui Yao Fang,
      some are transliterated words from the Hui language, such as Aligong, Alihun,
      Aergong, Futeier, Zulumalei and Talaxix: others are Chinese, such as fuling,
      tianma and mogu. These medical macrofungi were used in about one hundred
      prescriptions with different effects. Former scholars had made some creative
      contributions to unveil the prototypes of the medical macrofungi, but there are
      still some points open to question. For example, Aligong, Alihun and Aergong
      refer to Laricifomes officinalis rather than cap-shaped mushrooms. Futeier is an
      alexipharmic and edible macrofungus rather than a poisonous macrofungus. Talaxixi
      should refer to the parasite plant Cynomorium coccineum, not a macrofungus. Also,
      according to the catalog of Hui Hui Yao Fang, red mushrooms are considered
      poisonous, which does not coincide with the facts. Given that the book we
      preserved is incomplete, some exposition may be different from that in the
      original book.

PMID- 22613478
TI  - [Development of the concept of Evidence-Based Nursing].
AB  - In 1991, Professor Alba Diconso from MaMaster University put forward the idea of
      Evidence-Based Nursing (EBN). With the reference of evidence-based medicine
      (EBM), the concept of EBN was kept improving. In 1996, York University began to
      establish an EBN center to retrospect literature about nursing and publish their
      results. In 1997, Adelaide hospital in Australia set up the second EBN center. A
      series of monographic activities were held to offer empirical evidence for
      nursing practice, with great influence world-wide. In March 1997, an EBM Cochrane
      center was established by the Ministry of health of China in Huaxi Hospital
      affiliated to Shichuan University. Establishment of this center accelerated the
      spread of EBM and EBN nursing, and EBN began to be applied and developed in
      China.

PMID- 22613479
TI  - [Study of the contents of Da He Wai Ke in the Ming Dynasty].
AB  - Da He Wai Ke (the Great River External Medicine), an ancient book written by WANG
      Quan, a folk doctor, who was an apprentice of an unknown mysterious person in the
      Ming Dynasty. There are two volumes: thirty-six diseases were recorded in volume
      1 with a figure for each disease before the descriptive texts, and 72
      prescriptions were recorded in volume 2. The current research results about the
      origin of the contents of this book showed that: (1) contents in volume 1 texts
      were mainly from Chuang Ke Tong Xuan Lun (Enigmatic Theories for Sores Diseases);
      (2) there are no any direct clues about the source of the illustrations in volume
      1. Though some of them are similar to those in Chuang Yang Jing Yan Quan Shu (the
      Collected Works for Experience in Sores (Diseases), it is impossible that the
      illustrations are from that book; (3) the disease names listed in Da He Wai Ke
      were basically consistent with the ones in an ancient Korean book entitled 36
      Zhong Tu Lu (the 36 Illustrated Abscess Diseases); (4) the clues about where 67
      of 72 prescriptions in volume 2 came from were revealed; (5) it was found that 27
      of 37 prescriptions in the first half of volume 2 were rewritten from Chuang Ke
      Tong Xuan Lun, and 24 of them were completely corresponding to the prescriptions
      mentioned in volume 1; (6) 35 prescriptions in the second half of volume 2,
      showing no correlation with volume 1, were confirmed as subsequent supplements by
      Wang's descendants. Of the 35 prescriptions, 12 had close relationship to those
      in Chuang Yang Jing Yan Quan Shu : it is assumed that authors of the two books
      used the same books as their reference.

PMID- 22613480
TI  - [Origin of the  S curve in the ancient Taiji diagram-evolvement from the heaven
      and earth positioning diagram to the Taiji diagram].
AB  - The term 'Taiji' first appear in Zhouyi.Xici, saying that 'yi has Taiji which
      includes yin and yang'. Chinese ancestors formed the 'year' conception by
      observing sunrise, sundown and seasonal successions for a long period. 'yi has
      Taiji which includes yin and yang' was the resultant recording of their sun
      movement observations. People compared the heaven and earth to a circle and they
      divided the circle into four areas to record meteorological changes of the four
      seasons. A line was drawn from the spring equinox to the autumn equinox and the
      heaven and earth positioning diagram was created with the upper half as the
      heaven and the bottom half as the earth. The line was called the Taiji line.
      Considering that 'yang starts to grow at the winter solstice and yin starts to
      grow at the summer solstice', therefore people gradually changed the line to a S 
      curve.

PMID- 22613481
TI  - [Study of LI Gao's native place].
AB  - Li Gao, a famous doctor in Jin and Yuan Periods, was born in Zhengding County,
      Hebei Province according to History of the Ming Dynasty. But his tomb in Adang
      Village, Huangling County, Shanxi Province, the epitaph of tombstone (set up in
      1828, the 8th year of the Daoguang Period) and the Li's Genealogica Tree held by
      the villagers show that LI Gao was the 4th generation of local Li's family.
      Literatures of the Republic of China period, like Huangling County Annals, also
      recorded that Huangling county as LI Gao's native place. All of the historical
      relics, oral historical materials and literatures are of historical value and LI
      Gao's native place needs to be further investigated.

PMID- 22613482
TI  - [Textual Research on Wang Fengchun's Life].
AB  - WANG Fengchun (1884 - 1949), born in Wu County, Jiangsu Province, was one of the
      four famous doctors of Beijing in the Republic of China periods. He learned
      Confucianism during his childhood and then learned medicine from AI Buchan, a
      famous doctor in Wuzhong area. In 1908, he went to Beijing and was appointed as
      the prosecutor of the court of law and a medical official, but also had learnt
      medicine from LI Jun, the head of the Business Ministry. In 1910, Wang resigned
      and lived as doctor in Beijing. According to the literature, from 1935 to 1942,
      Wang had been appointed 11 times as a member of Beiping (Beijing) TCM examination
      committee or test committee. In 1938, he was appointed as president of the
      Beijing Branch of the National Medical Professional Association and created the
      Beijing Medicine Monthly in 1939. In September 1939, Wang began to make
      preparations for a TCM symposium, i.e. the Medicine Symposium which was
      established officially in October 1939. In 1941, he was appointed as the director
      of the Beijing Traditional Chinese Medicines Workshop, employing famous doctors
      to cultivate reserve talents of medicines. Being a realist, he often exchanged
      opinions with TCM and western medical doctors and also made a contribution to
      medical education.

PMID- 22613483
TI  - Characterization of Foxp3 gene from grass carp (Ctenopharyngodon idellus): a
      rapamycin-inducible transcription factor in teleost immune system.
AB  - In this study, we cloned grass carp foxp3 (gcfoxp3) gene including 5' flanking
      region and determined its expression profiles in vivo under immunosuppressive
      conditions. Sequence analysis revealed that the promoter of gcfoxp3 contains AP
      1, AML-1/Runx1, NF-kappab and GATA-3 binding sites, which positively or
      negatively regulate mammalian foxp3 expression. In addition, the intron II of
      gcfoxp3 contains some putative binding sites including AP-1, NFAT, Smad3, RAR,
      CREB/ATF and FOXO1, which are corresponding to their locations in the proximal
      intronic enhancers of human foxp3. In an in vivo model of grass carp, an
      immunosuppressive agent rapamycin was showed to stimulate gcfoxp3 mRNA expression
      in thymus, gill, head kidney and spleen after bacterial challenge. Moreover,
      rapamycin increased gcFoxp3 protein levels with an additive manner in the
      infected fish. These findings support the involvement of fish Foxp3 in immune
      response and highlight a possible signaling pathway that regulates teleost Foxp3
      expression.

PMID- 22613485
TI  - The epithelial-mesenchymal transition under control: global programs to regulate
      epithelial plasticity.
AB  - The epithelial to mesenchymal transition or EMT has become one of the most
      exciting fields in cancer research. Nevertheless, its relevance in tumor biology
      and the metastatic process still faces some controversy. Clarification may arise
      when considering the EMT as a reversible and often incomplete process,
      essentially a manifestation of strong epithelial plasticity. Transient cellular
      states are generated to fulfill specific requirements in each and all the steps
      of the metastatic process, from primary tumor cell detachment to dissemination
      and colonization. Opposing multiple cellular programs that promote or prevent
      EMT, thereby destabilizing or reinforcing epithelial integrity, play a central
      role in the inherent cellular dynamics of cancer progression. These cell biology
      programs not only drive cells towards the epithelial or the mesenchymal state but
      also impinge into multiple cellular and global responses including proliferation,
      stemness, chemo and immunotherapy resistance, inflammation and immunity, all
      relevant for the development of the metastatic disease.

PMID- 22613486
TI  - An unusual cause of reversible axonal neuropathy and hypertension in a 10-year
      old girl.
AB  - A 10-year-old girl, who was referred with refractory epilepsy, had 1.5 years of
      episodic abnormal behavior. On examination, she also had hypertension and
      peripheral neuropathy. Hypoglycemia with correspondingly high insulin levels was
      documented during a confusional episode. MRI of the abdomen revealed an islet
      cell tumor in the body of the pancreas. One year after tumor excision, both the
      neuropathy and hypertension showed remarkable improvement. A final diagnosis of
      insulinoma with hypoglycemic axonal neuropathy and hypertension (reversed with
      tumor excision) was made. Insulinoma is the commonest cause of hyperinsulinemic
      hypoglycemia in adults, but is rare in childhood. To our knowledge, distal
      symmetrical motor-sensory axonal neuropathy has been described in only 40
      patients, and hypertension has not been reported with insulinoma.

PMID- 22613484
TI  - A new paradigm for mechanobiological mechanisms in tumor metastasis.
AB  - Tumor metastases and epithelial to mesenchymal transition (EMT) involve tumor
      cell invasion and migration through the dense collagen-rich extracellular matrix
      surrounding the tumor. Little is neither known about the mechanobiological
      mechanisms involved in this process, nor the role of the mechanical forces
      generated by the cells in their effort to invade and migrate through the stroma.
      In this paper we propose a new fundamental mechanobiological mechanism involved
      in cancer growth and metastasis, which can be both protective or destructive
      depending on the magnitude of the forces generated by the cells. This new
      mechanobiological mechanism directly challenges current paradigms that are
      focused mainly on biological and biochemical mechanisms associated with tumor
      metastasis. Our new mechanobiological mechanism describes how tumor expansion
      generates mechanical forces within the stroma to not only resist tumor expansion
      but also inhibit or enhance tumor invasion by, respectively, inhibiting or
      enhancing matrix metalloproteinase (MMP) degradation of the tensed interstitial
      collagen. While this mechanobiological mechanism has not been previously applied
      to the study of tumor metastasis and EMT, it may have the potential to broaden
      our understanding of the tumor invasive process and assist in developing new
      strategies for preventing or treating cancer metastasis.

PMID- 22613487
TI  - Transtentorial herniation in patients with hypertensive putaminal haemorrhage is
      predictive of elevated intracranial pressure following haematoma removal.
AB  - We investigated surgical outcomes of haematoma evacuation in patients with
      hypertensive putaminal haemorrhage, with emphasis on the development of
      postoperative refractory intracranial hypertension. Twenty-two consecutive
      patients with hypertensive putaminal haemorrhage underwent microsurgical clot
      removal without decompressive craniectomy. Medical histories, radiographic
      findings, and surgical notes were reviewed. Twenty patients survived to
      discharge. Twelve patients with preoperative transtentorial herniation,
      demonstrating a greater haematoma volume and lower Glasgow Coma Scale (GCS)
      score, had significantly elevated postoperative intracranial pressure. Five of
      these patients developed refractory intracranial hypertension (42%), and two of
      these patients died. Conversely, none of the 10 patients without preoperative
      transtentorial herniation experienced refractory intracranial hypertension, and
      they had a better outcome at discharge. The preoperative presence of clinical
      transtentorial herniation may predict the development of postoperative refractory
      intracranial hypertension, which may require decompressive craniectomy.

PMID- 22613488
TI  - Medullary neurosarcoidosis presenting with intractable hiccoughs.
AB  - Hiccoughs (singultus) are a complex physiological process characterized by sudden
      brief involuntary contractions of the diaphragm. They most commonly occur from
      peripheral mechanisms that result in diaphragmatic irritation, but also occur
      from brain stem lesions such as that seen in Wallenberg's syndrome. They are
      uncommon in sarcoidosis and it is remarkably rare when hiccoughs are the
      presenting symptom of neurosarcoidosis. We report a patient with sarcoidosis who
      presented with intractable hiccoughs due to an inflammatory medullary lesion.
      Evaluation revealed an enhancing lesion in the dorsomedial medulla that resolved
      after aggressive immune-modulating therapy. In the absence of a clear peripheral
      lesion that would potentially affect the diaphragm, the diagnosis of
      neurosarcoidosis involving the brainstem should be considered in patients with
      sarcoidosis.

PMID- 22613489
TI  - Roles of brain-derived neurotrophic factor/tropomyosin-related kinase B
      (BDNF/TrkB) signalling in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is one of the most common causes of dementia in the
      elderly. It is characterized by extracellular deposition of the neurotoxic
      peptide, amyloid-beta (Abeta) peptide fibrils, and is accompanied by extensive
      loss of neurons in the brains of affected individuals. However, the pathogenesis
      of AD is not fully understood. The aim of this review is to discuss the possible
      role of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B
      (TrkB) signalling in the development of AD, focusing on BDNF/TrkB signalling in
      the production of Abeta, tau hyperphosphorylation and cognition decline, and
      exploring new possibilities for AD intervention.

PMID- 22613490
TI  - Rosette-forming glioneuronal tumour of the lateral ventricle in a patient with
      neurofibromatosis 1.
AB  - We report a 33-year-old man with neurofibromatosis type 1 (NF-1) with a rosette
      forming glioneuronal tumour (RGNT) in the lateral ventricle. The patient had been
      treated with radiotherapy and chemotherapy for a typical juvenile pilocytic
      astrocytoma of the hypothalamus seven years prior. MRI revealed a contrast
      enhancing mass in the anterior horn of the left lateral ventricle. Histological
      examination demonstrated two distinct regions characterised by a rosette-forming
      neurocytic component and an astrocytic predominant component. Immunohistochemical
      studies showed glial fibrillary acidic protein and S-100 positivity in the
      astrocytic component and neuron-specific enolase was positive in the neurocytic
      cells. Although RGNT has been reported at other sites within the central nervous
      system, this report documents a previously undescribed lateral ventricular
      location of a rare RGNT in an asymptomatic patient with NF-1.

PMID- 22613491
TI  - Brain MRI abnormalities in Brazilian patients with neuromyelitis optica.
AB  - Brain abnormalities in neuromyelitis optica (NMO) have been reported previously,
      but the pathophysiological mechanism and clinical relevance of these
      abnormalities are poorly understood. We assessed the prevalence and patterns of
      brain MRI abnormalities in a Brazilian cohort of patients with NMO. Conventional
      brain MRI and medical records from 24 Brazilian patients with NMO were
      retrospectively evaluated. Brain MRI were classified into four subgroups: normal,
      non-specific lesions, multiple sclerosis (MS)-like lesions, and typical lesions.
      Brain lesions were detected in 19 patients (79.2%). Fourteen patients (58.3%) had
      non-specific lesions, three (12.5%) had MS-like lesions, and two (8.3%) had
      typical lesions. Differences between these subgroups with respect to the Expanded
      Disability Status Scale (EDSS) scores (p=0.86) were not significant. This study
      demonstrates a high prevalence of brain abnormalities in Brazilian patients with
      NMO; however, we did not find a significant relationship between these
      abnormalities and EDSS scores.

PMID- 22613492
TI  - Uterine artery, umbilical, and fetal cerebral Doppler velocities after epidural
      analgesia during labor.
AB  - OBJECTIVE: To evaluate the effects of epidural analgesia on uterine artery,
      umbilical, and fetal cerebral Doppler velocities during labor. METHODS: In a
      prospective study at Beaujon Hospital, Paris, France, between September and
      December 2010, uterine artery, umbilical, and fetal cerebral Doppler flow
      velocities were measured in 12 pregnant women during spontaneous labor with
      epidural analgesia. The data were registered in a period of uterine relaxation
      before, and 20 and 60 minutes after the first administration of epidural
      analgesic drugs. The changes in Doppler velocimetry values and fetal heart rate
      after epidural analgesia were analyzed. RESULTS: Uterine artery velocities, but
      neither umbilical nor fetal cerebral Doppler velocities, were decreased
      significantly at 20 minutes and 1 hour after epidural analgesia (P<0.005). Women
      with the greatest decrease in uterine artery Doppler flow velocities delivered
      neonates with the lowest values of umbilical artery blood pH. CONCLUSION: The
      data suggest that the Doppler flow velocity of uterine arteries is affected by
      epidural analgesia during labor. Numerous Doppler flow studies of the effect of
      neuraxial blockade during labor on umbilical and uterine arteries have been
      published with incredibly variable and inconsistent results.

PMID- 22613493
TI  - Organization and evolution of organized cervical cytology screening in Thailand.
AB  - OBJECTIVE: To describe phase 1 of an organized cytology screening project
      initiated in Thailand by the Ministry of Public Health and the National Health
      Security Office. METHODS: Women aged 35-60 years were encouraged to undergo
      cervical screening in primary care units and hospitals through awareness
      programs. Papanicolaou smears were processed and reported at district or
      provincial cytology laboratories. Women with normal test results were advised to
      undergo repeat screening after 5 years, while those with precancerous and
      cancerous lesions were referred for colposcopy, biopsy, and treatment.
      Information on screening, referral, investigations, and therapy were logged in a
      computer database. RESULTS: Between 2005 and 2009, 69.2% of the 4030833 targeted
      women were screened. In all, 20991 women had inadequate smears; 27253 had low
      grade squamous intraepithelial lesions; 15706 had high-grade squamous
      intraepithelial lesions; and 2920 had invasive cancers. Information on the
      management of precancerous lesions was available for only 17.4% of women referred
      for colposcopy. CONCLUSION: Although follow-up data on women with positive test
      results were inadequately documented, the present findings indicate that
      provision of cytology services through the existing healthcare system is
      feasible.

PMID- 22613494
TI  - The optimal threshold values for the severity of urinary incontinence based on
      the 1-hour pad test.
AB  - OBJECTIVE: To explore the correlation between the 1-hour pad test and Stamey
      incontinence grading and to obtain the optimal threshold values for the severity
      of urinary incontinence. METHODS: In a cross-sectional retrospective study at
      Peking Union Medical College Hospital, 1-hour pad test results and Stamey grades
      of female patients who had undergone therapy for urinary incontinence between
      June 2005 and December 2010 were reviewed. The correlation between the objective
      and subjective measurements was assessed via a Spearman rank correlation test.
      The optimal diagnostic threshold was evaluated by ROC curve, and areas under the
      ROC curve reflected the accuracy of the 1-hour pad test. RESULTS: A strong
      positive correlation was found between the 1-hour pad test results and the
      subjective grades of 320 patients (correlation coefficient 0.757, P<0.001). On
      the basis of the 1-hour pad test, the optimal diagnostic cutoff points for the
      severity of urinary incontinence were 3.4 g and 10.2g. CONCLUSION: The 1-hour pad
      test could assess the severity of urinary incontinence accurately. The threshold
      values should be, approximately, less than 3g for mild, 3-10 g for moderate, and
      more than 10 g for severe urinary incontinence.

PMID- 22613495
TI  - Kinetics of parasite burdens in blood and tissues during murine toxoplasmosis.
AB  - A sensitive real-time PCR technique was used to examine the distribution of
      Toxoplasma gondii in the blood and tissues of mice during acute and chronic
      infection. Groups of Swiss Albino mice, inoculated i.p. with 10(2) or 10(6)
      tachyzoites of the RH strain as a typical type-1 strain, or fed 10 cysts of the
      Me49 strain as a typical type-2 strain, were killed at different time points post
      infection (p.i.), and blood and organs including the lungs, brain and liver were
      harvested for DNA extraction. Toxoplasma DNA was quantified by a real-time PCR
      targeted at the 529bp gene fragment, with a detection limit of a single parasite
      per g/ml of tissue. The results showed a strain- and dose-dependent spread of
      Toxoplasma. In infection with type-1 parasites, in case of a high infective dose,
      Toxoplasma DNA was detected within 24h p.i. in all analyzed tissues including the
      brain. Conversely, in case of a low infective dose, parasitaemia was undetectable
      early p.i., at a time when Toxoplasma DNA was detected in the tissues, but
      reached very high levels as infection progressed. With both infective doses, pre
      death parasite burdens were higher in the blood than in the tissues, whereas the
      same loads in the lungs suggest that reaching these Toxoplasma burdens may be
      critical for survival. In infection with Me49 parasites, steady high parasite
      burdens were noted up to the end of the experiment at d42 only in the brain,
      parasitaemia was low but detectable throughout, and Toxoplasma DNA was completely
      cleared only from the liver. These data are important to better understand the
      pathogenesis of toxoplasmosis, and also as baseline data for the experimental
      evaluation of novel chemotherapeutics.

PMID- 22613496
TI  - Expression levels of HMGA2 and CD9 and its clinicopathological significances in
      the benign and malignant lesions of the gallbladder.
AB  - BACKGROUND: The objective of this study was to investigate CD9 and HMGA2
      expression and its clinicopathological significance in benign and malignant
      lesion tissues of the gallbladder. METHODS: The resected specimens of 108 cases
      of gallbladder adenocarcinoma, 46 cases of adjacent tissue, 15 cases of polyps
      and 35 cases of chronic cholecystitis were made into conventional paraffin
      embedded sections, using the method of EnVision immunohistochemistry to stain
      HMGA2 and CD9. RESULTS: HMGA2 expression of gallbladder adenocarcinoma was
      significantly higher than that of adenocarcinoma adjacent tissues (= 16.13, P
      <0.01), polyps (= 8.19, P <0.01) and chronic cholecystitis (= 21.41, P <0.01);
      but CD9 expression was the opposite (P <0.05 or P <0.01). The positive rate of
      HMGA2 expression from the cases that had well-differentiated adenocarcinoma, with
      the largest tumor diameter <2 cm, and without lymph node metastasis, and that did
      not invade the surrounding tissue was significantly lower than that of HMGA2
      expression from the cases that had poorly differentiated adenocarcinoma, with the
      largest tumor diameter >=2 cm, lymph node metastasis, and that invaded the
      surrounding tissues (P <0.05 or P <0.01). The positive rate of CD9 expression
      from the cases that had well-differentiated adenocarcinoma, with the largest
      tumor diameter <2 cm, and without lymph node metastasis, and that did not invade
      the surrounding tissue was significantly higher than that of CD9 expression from
      the cases that had poorly differentiated adenocarcinoma, with the largest tumor
      diameter >=2 cm, lymph node metastasis, and which invaded the surrounding tissues
      (P <0.05 or P <0.01). The Kaplan-Meier survival analysis showed that after
      surgery, the survival period of HMGA2 expression-positive cases was significantly
      lower than that of HMGA2 expression-negative cases (P = 0.020), but the survival
      period of CD9 expression-positive cases was significantly higher than that of
      cases with CD9 expression-negative (P = 0.019). Cox multivariate regression
      analysis showed that the HMGA2 positive expression and/or CD9 negative expression
      was an important indicator reflecting the poor prognosis of gallbladder cancer.
      CONCLUSION: The expression of HMGA2 and/or CD9 might be closely related to the
      carcinogenesis, clinical biological behaviors and prognosis of gallbladder
      adenocarcinoma.

PMID- 22613497
TI  - Nek2 localises to the distal portion of the mother centriole/basal body and is
      required for timely cilium disassembly at the G2/M transition.
AB  - The NIMA-related kinase Nek2 promotes centrosome separation at the G2/M
      transition and, consistent with this role, is known to be concentrated at the
      proximal ends of centrioles. Here, we show by immunofluorescence microscopy that
      Nek2 also localises to the distal portion of the mother centriole. Its
      accumulation at this site is cell cycle-dependent and appears to peak in late G2.
      These findings are consistent with previous data implicating Nek2 in promoting
      reorganisation of centrosome-anchored microtubules at the G2/M transition, given
      that microtubules are anchored at the subdistal appendages of the mother
      centriole in interphase. In addition, we report that siRNA-mediated depletion of
      Nek2 compromises the ability of cells to resorb primary cilia before the onset of
      mitosis, while overexpression of catalytically active Nek2A reduces ciliation and
      cilium length in serum-starved cells. Based on these findings, we propose that
      Nek2 has a role in promoting cilium disassembly at the onset of mitosis. We also
      present evidence that recruitment of Nek2 to the proximal ends of centrioles is
      dependent on one of its substrates, the centrosome cohesion protein C-Nap1.

PMID- 22613498
TI  - Tetralogy of Fallot with cor triatriatum dexter in an adult patient: a case
      report.
AB  - Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect
      with only approximately 3% of uncorrected patients surviving past age 40. In this
      case report, we present a 48-year-old mentally retarded man suffering from
      congenital spastic quadriplegia who was diagnosed with a unique combination of
      symptomatic TOF and cor triatriatum dexter (CTD). Reduced preload because of CTD
      with spastic quadriplegia that prevented physical exertion is believed to have
      facilitated this patient's unusually long survival.

PMID- 22613499
TI  - Renal denervation and treatment-resistant hypertension: a matter of importance
      for interventional radiology.

PMID- 22613500
TI  - Allergic fungal sinusitis. Answer to March e-quid.

PMID- 22613501
TI  - Tissue Doppler systolic velocity change during dobutamine stress echocardiography
      predicts contractile reserve and exercise tolerance in patients with heart
      failure.
AB  - AIMS: Dobutamine stress echocardiography (DSE) is widely used to evaluate
      myocardial contractile reserve in patients with heart failure (HF). The aim of
      the study was to assess the relationship between the tissue Doppler (TD) mitral
      annulus systolic velocity (Sm) change during DSE, contractile reserve, and
      aerobic exercise capacity in HF patients. METHODS AND RESULTS: Sixty-four HF
      patients (age 67 +/- 9 years, 58% with an ischaemic aetiology, and a mean value
      of the ejection fraction 29 +/- 7%) underwent high-dose DSE. The mean value of
      the TD mitral annulus septal-lateral Sm change was analysed at rest and at peak
      DSE. All patients underwent also the cardiopulmonary exercise test. With a
      receiver operating characteristic analysis, a value of 2.02 cm/s obtained as a
      stress-rest difference in a mean value of the peak systolic velocity of the
      mitral annulus (Sm) was the best value for diagnosing the myocardial contractile
      reserve [area under the curve 0.69 (95% CI 0.56-0.80), sensitivity 69% (95% CI 54
      81), specificity 80% (95% CI 45-97)]. The patient population was divided into two
      groups: with rest-stress Sm change during DSE <= 2.02 cm/s and with rest-stress
      Sm change >2.02 cm/s. Patients with Sm rest-stress >2.02 change during DSE,
      compared with patients with rest-stress change <=2.02, showed a lower incidence
      of severe diastolic dysfunction at rest (16 vs. 46%, P= 0.039) and lower E/Ea
      values (11 +/- 5 vs. 15 +/- 6, P = 0.005), similar ejection fraction at rest but
      higher ejection fraction at peak DSE (53 +/- 14 vs. 41 +/- 12%, P = 0.001),
      better myocardial contractile reserve assessed by a pressure-volume relationship
      (1.89 +/- 2.01 vs. 0.58 +/- 1.38 mmHg/mL/m(2), P = 0.004), with a lower end
      systolic volume (-46 +/- 20 vs. -24 +/- 19%, P< 0.001), a higher increase in the
      ejection fraction (23 +/- 10 vs. 12 +/- 10%, P = 0.001) during DSE, and better
      peak oxygen consumption (16 +/- 4 vs. 13 +/- 2 mL/kg/min, P = 0.01). CONCLUSION:
      In patients with HF, the rest-stress variation of mitral annulus systolic
      velocities during DSE predicts the presence of myocardial contractile reserve and
      exercise tolerance.

PMID- 22613502
TI  - Detection of Leishmania infantum DNA mainly in Rhipicephalus sanguineus male
      ticks removed from dogs living in endemic areas of canine leishmaniosis.
AB  - BACKGROUND: Sand flies are the only biologically adapted vectors of Leishmania
      parasites, however, a possible role in the transmission of Leishmania has been
      proposed for other hematophagous ectoparasites such as ticks. In order to
      evaluate natural infection by Leishmania infantum in Rhipicephalus sanguineus
      ticks, taking into account its close association with dogs, 128 adult R.
      sanguineus ticks removed from 41 dogs living in endemic areas of canine
      leishmaniosis were studied. METHODS: Individual DNA extraction was performed from
      each tick and whole blood taken from dogs. Dog sera were tested for IgG
      antibodies to L. infantum antigen by ELISA and L. infantum real-time PCR was
      performed from canine whole blood samples and ticks. RESULTS: Leishmania infantum
      PCR was positive in 13 ticks (10.1%) including one female, (2.0%) and 12 males
      (15.2%), and in only five dogs (12.2%). Male ticks had a significantly higher
      infection rate when compared to female R. sanguineus. The percentage of L.
      infantum seroreactive dogs was 19.5%. All but two PCR positive dogs were
      seroreactive. Leishmania infantum PCR positive ticks were removed from
      seropositive and seronegative dogs with a variety of PCR results. CONCLUSIONS:
      This study demonstrates high prevalence of L. infantum DNA in R. sanguineus ticks
      removed from L. infantum seropositive and seronegative dogs. The presence of L.
      infantum DNA was detected mainly in male ticks possibly due to their ability to
      move between canine hosts and feed on several canine hosts during the adult life
      stage. Additional studies are needed to further explore the role of R. sanguineus
      ticks and in particular, male adults, in both the epidemiology and immunology of
      L. infantum infection in dogs in endemic areas.

PMID- 22613503
TI  - Inspiratory limb carbon dioxide entrainment during high-frequency oscillatory
      ventilation: characterization in a mechanical test lung and swine model.
AB  - BACKGROUND: High-frequency oscillatory ventilation (HFOV) has been utilized as a
      rescue oxygenation therapy in adults with ARDS over the last decade. The HFOV
      oscillating piston can generate negative pressure during the exhalation cycle,
      which has been termed active exhalation. We hypothesized  that this
      characteristic of HFOV entrains CO(2) into the inspiratory limb of the circuit
      and increases the total dead space. The purpose of this study was to determine if
      retrograde CO(2) entrainment occurs and how it is altered by HFOV parameter
      settings. METHODS: An HFOV  was interfaced to a cuffed endotracheal tube and
      connected to a mechanical test lung. Negative pressure changes within the
      circuit's inspiratory limb were measured while HFOV settings were manipulated.
      Retrograde CO(2) entrainment was evaluated by insufflating CO(2) into  the test
      lung to achieve 40 mm Hg at the carina. Inspiratory limb CO(2) entrainment was
      measured at incremental distances from the Y-piece. HFOV settings and cuff leak
      were varied to assess their effect on CO(2) entrainment. Control experiments were
      conducted using a conventional  ventilator. Test lung results were validated on a
      large hypercapnic swine. RESULTS: Negative pressure was detectable within the
      inspiratory limb of the HFOV circuit and varied inversely with mean airway
      pressure (P(-)(aw))  and directly with oscillatory pressure amplitude (DeltaP).
      CO(2) was readily detectable within the inspiratory limb and was proportional to
      the negative pressure that was generated. Factors that decreased CO(2)
      entrainment in both the test lung and swine included low DeltaP,  high mean
      airway pressure, high oscillatory frequency (Hz), high bias flow, and
      endotracheal tube cuff leak placement. CO(2) entrainment was also reduced by
      utilizing a higher bias flow strategy at any targeted mean airway pressure.
      CONCLUSIONS: Retrograde CO(2) entrainment  occurs during HFOV use and can be
      manipulated with the ventilator settings. This phenomenon may have clinical
      implications on the development or persistence of hypercapnia.

PMID- 22613504
TI  - French children's exposure to metals via ingestion of indoor dust, outdoor
      playground dust and soil: contamination data.
AB  - In addition to dietary exposure, children are exposed to metals via ingestion of
      soils and indoor dust, contaminated by natural or anthropogenic outdoor and
      indoor sources. The objective of this nationwide study was to assess metal
      contamination of soils and dust which young French children are exposed to. A
      sample of 484 children (6 months to 6 years) was constituted in order to obtain
      representative results for young French children. In each home indoor settled
      dust was sampled by a wipe in up to five rooms. Outdoor playgrounds were sampled
      with a soil sample ring (n=315) or with a wipe in case of hard surfaces (n=53).
      As, Cd, Cr, Cu, Mn, Pb, Sb, Sr, and V were measured because of their potential
      health concern due to soil and dust ingestion. The samples were digested with
      hydrochloric acid, and afterwards aqua regia in order to determine both leachable
      and total metal concentrations and loadings by mass spectrometry with a
      quadrupole ICP-MS. In indoor settled dust most (total) loadings were below the
      Limit of Quantification (LOQ), except for Pb and Sr, whose median loadings were
      respectively 9 and 10 MUg/m2. The 95th percentile of loadings were 2 MUg/m2 for
      As, <0.8 for Cd, 18 for Cr, 49 for Cu, <64 for Mn, 63 for Pb, 2 for Sb, 56 for
      Sr, and <8 for V. Median/95th percentile of loadings in settled dust on outdoor
      playgrounds were 2/16, <0.8/1.3, 17/53, 49/330, 99/424, 32/393, 2/13, 86/661 and
      10/37 MUg/m2 for As, Cd, Cr, Cu, Mn, Pb, Sb, Sr, and V respectively. In outdoor
      playground soil median/95th percentile of concentrations (MUg/g) were 8/26,
      <0.65/1, 25/52, <26/53,391/956, 27/254, 0.7/4, 54/295, 23/57 for As, Cd, Cr, Cu,
      Mn, Pb, Sb, Sr, and V respectively. These results are comparable with those
      observed in other countries. Because of their representative nature, we can
      assess children's exposures to these metals via soil and dust and the associated
      risks in urban and rural environments. Ratios of leachable/total concentrations
      and loadings, calculated on >LOQ measurements, differed among metals. To a lesser
      extent, they were also affected by type of matrix, with (except for Cd) a greater
      leachability of dust (especially indoor) compared to soils.

PMID- 22613505
TI  - Clinical utility of a microbubble-enhancing contrast ("SonoVue") in treatment of
      uterine fibroids with high intensity focused ultrasound: a retrospective study.
AB  - PURPOSE: To evaluate the clinical value of the contrast agent SonoVue in the
      treatment of uterine fibroids with ultrasound-guided high intensity focused
      ultrasound (HIFU) therapeutic ablation. MATERIALS AND METHODS: A total of 291
      patients with solitary uterine fibroid from three centers were treated with
      ultrasound-guided HIFU. Among them, 129 patients from Suining Central Hospital of
      Sichuan were treated without using SonoVue. 162 patients from the First Hospital
      of Chongqing Medical University and Chongqing Haifu Hospital were treated with
      using SonoVue before, during and after HIFU procedure to assess the extent of
      HIFU. RESULTS: The non-perfused volume (indicative of successful ablation) was
      observed in all treated uterine fibroids immediately after HIFU ablation; median
      fractional ablation, defined as non-perfused volume divided by the fibroid volume
      immediately after HIFU treatment, was 86.0% (range, 28.8-100.0%) in the group
      with using SonoVue, and 83.0% (8.7-100.0%) without SonoVue. The rate of massive
      gray scale changes was higher with SonoVue than without the agent. The sonication
      time to achieve massive gray scale changes was shorter with SonoVue than without.
      The sonication time for ablating 1cm(3) of fibroid volume was significantly
      shorter with using SonoVue than without. No major complications were observed in
      any patients. CONCLUSIONS: Based on our results, SonoVue may enhance the outcome
      of HIFU ablation and can be used to assess the extent of treatment.

PMID- 22613506
TI  - Autoimmune pancreatitis: assessment of the enhanced duct sign on multiphase
      contrast-enhanced computed tomography.
AB  - PURPOSE: To assess the usefulness of the computed tomography (CT) finding of main
      pancreatic duct (MPD) wall enhancement, termed the "enhanced duct sign", for
      diagnosis of autoimmune pancreatitis (AIP) in comparison with diagnosis of
      pancreatic carcinoma and chronic pancreatitis. MATERIALS AND METHODS: Two
      radiologists independently evaluated the presence or absence of the enhanced duct
      sign on multiphase contrast-enhanced CT in patients with AIP (n=55), pancreatic
      carcinoma (n=50), and chronic pancreatitis (n=50). The sensitivity, specificity,
      accuracy, positive predictive value, and negative predictive value of AIP were
      calculated. In patients demonstrating the enhanced duct sign, additional findings
      were evaluated by consensus. RESULTS: The enhanced duct sign was more frequently
      observed in patients with AIP (37/55, 67%) than in patients with pancreatic
      carcinoma (5/50, 10%) or chronic pancreatitis (0/50, 0%) (P<0.05). The
      sensitivity, specificity, accuracy, positive predictive value, and negative
      predictive value of the finding were 0.67, 0.95, 0.85, 0.88, and 0.84,
      respectively. In AIP, the lumen within the enhanced duct was completely or
      partially invisible in 29 of 37 (78%) patients, and the enhanced duct was
      observed within the affected pancreatic parenchyma in 35 of 37 (95%) patients. In
      pancreatic carcinoma, the lumen within the enhanced duct was visible in all
      patients (5/5, 100%), and the enhanced duct was observed downstream of the tumor
      (5/5, 100%). CONCLUSION: The enhanced duct sign is highly specific of AIP.

PMID- 22613507
TI  - Hepatic CT perfusion measurements: a feasibility study for radiation dose
      reduction using new image reconstruction method.
AB  - OBJECTIVES: To assess the effects of image reconstruction method on hepatic CT
      perfusion (CTP) values using two CT protocols with different radiation doses.
      MATERIALS AND METHODS: Sixty patients underwent hepatic CTP and were randomly
      divided into two groups. Tube currents of 210 or 250 mA were used for the
      standard dose group and 120 or 140 mA for the low dose group. The higher currents
      were selected for large patients. Demographic features of the groups were
      compared. CT images were reconstructed by using filtered back projection (FBP),
      image filter (quantum de-noising, QDS), and adaptive iterative dose reduction
      (AIDR). Hepatic arterial and portal perfusion (HAP and HPP, ml/min/100ml) and
      arterial perfusion fraction (APF, %) were calculated using the dual-input maximum
      slope method. ROIs were placed on each hepatic segment. Perfusion and Hounsfield
      unit (HU) values, and image noises (standard deviations of HU value, SD) were
      measured and compared between the groups and among the methods. RESULTS: There
      were no significant differences in the demographic features of the groups, nor
      were there any significant differences in mean perfusion and HU values for either
      the groups or the image reconstruction methods. Mean SDs of each of the image
      reconstruction methods were significantly lower (p<0.0001) for the standard dose
      group than the low dose group, while mean SDs for AIDR were significantly lower
      than those for FBP for both groups (p=0.0006 and 0.013). Radiation dose
      reductions were approximately 45%. CONCLUSIONS: Image reconstruction method did
      not affect hepatic perfusion values calculated by dual-input maximum slope method
      with or without radiation dose reductions. AIDR significantly reduced images
      noises.

PMID- 22613508
TI  - Phantom study of the impact of reconstruction parameters on the detection of mini
      and micro-volume lesions with a low-dose PET/CT acquisition protocol.
AB  - PURPOSE: Every PET scanner suffers of the partial volume effect (PVE), that is a
      loss of contrast in small lesions causing a worsening in standardized uptake
      value (SUV) accuracy, that is critical if quantitative PET/CT imaging is used for
      diagnosis and therapy. METHODS: In order to quantify PVE and optimize our
      clinical protocols to minimize this effect in a last generation PET/CT scanner,
      we utilized a cylindrical phantom equipped with ten mini- and micro-volume hollow
      spheres. The lesion detectability and the SUV accuracy were evaluated at a fixed
      spheres to background intrinsic contrast (activity concentration ratio 8:1) but
      in different scan conditions: (a) acquisition modality (3D vs. 2D), (b) number of
      subset per iteration, (c) type of post-reconstruction filter and (d) activity
      concentration (i.e. total counts). Also the effect of different absorber
      thickness was evaluated. RESULTS: Small lesion detectability resulted better in
      images acquired in 3D mode rather than 2D, mainly because of the lower noise
      produced by the fully-3D algorithm. The number of reconstruction iterations and
      the post-processing filter used affected both the contrast underestimation and
      the spatial resolution. Decreasing the (18)F activity injected according to the
      low-dose protocol, the small lesions could be distinguished from the background
      down to a diameter of 6.2mm and the SUV accuracy did not deteriorate. Adding
      absorber thickness around the phantom, the image noise slightly increased while
      SUV accuracy did not change. CONCLUSIONS: The hybrid PET/CT scanner we evaluated
      showed good performances, mainly in 3D acquisition modality. The phantom
      measurements showed that the most appropriate reconstruction protocol derived
      from a compromise between the contrast accuracy and the noise variance in PET
      images. The low-dose protocol clinically used demonstrated no loss in SUV
      accuracy and an adequate lesion detectability for lesions down to 6.2mm in
      diameter.

PMID- 22613509
TI  - Renal and perirenal space involvement in acute pancreatitis: An MRI study.
AB  - OBJECTIVES: To study the prevalence and characteristics of renal and perirenal
      space involvement and its relation to the severity of acute pancreatitis (AP)
      using MRI. METHODS: 115 patients with AP who underwent MRI with the clinical
      kidney function test were retrospectively analyzed in this study. MRI sequences
      included conventional and diffusion weighted imaging (DWI) sequences. The renal
      and perirenal space involvement in AP was noted on MRI. The renal apparent
      diffusion coefficient (ADC) on DWI was measured for each kidney. The severity of
      AP on MRI was graded using MR severity index (MRSI). The relationships among the
      renal and perirenal space involvement on MRI, the renal ADC, MRSI and the results
      of the kidney function test were analyzed. RESULTS: In the 115 patients with AP,
      the renal and perirenal space abnormalities detected included renal parenchymal
      abnormalities (0.8%), abnormalities of the renal collecting system (2.6%), renal
      vascular abnormalities (1.7%), thickened renal fascia (99%), perirenal stranding
      (62%) and perirenal fluid collection (40%). The prevalence of perirenal space
      abnormalities was correlated with the severity of AP based on MRSI (P<0.05). The
      renal ADC values were lower in patients with abnormal kidney function than in
      those without kidney injury (P<0.05). The prevalence of kidney function
      abnormalities was 9.4%, 32% and 100% in mild, moderate, and severe AP cases,
      respectively (P=0.00). CONCLUSION: Perirenal space involvement is much more than
      renal parenchymal involvement in AP. The prevalence of perirenal space
      involvement in AP on MRI has a positive correlation with the severity of AP
      according to MRSI.

PMID- 22613511
TI  - The relationship between height and neighborhood context across racial/ethnic
      groups: a multi-level analysis of the 1999-2004 U.S. National Health and
      Nutrition Examination Survey.
AB  - While a growing literature has documented a link between neighborhood context and
      health outcomes, little is known about the relationship between neighborhood
      characteristics and height. Using individual data from the 1999-2004 U.S.
      National Health and Nutrition Examination Survey merged with tract-level data
      from the U.S. Census, we investigate several neighborhood characteristics,
      including neighborhood socioeconomic status (NSES), education index of
      concentration at the extremes (ICE), and population density, as potential
      predictors of height. Employing a series of two-level random intercept models, we
      find a one standard deviation increase in NSES to be associated with a 0.6-1.4 cm
      height advantage for white and foreign-born Mexican-American females and for U.S.
      born Mexican-American males, net of individual-level controls. Similarly, a 10
      point increase in neighborhood education ICE was associated with 0.23-0.32 cm
      greater height for white and foreign-born Mexican-American females and U.S. born
      Mexican-American males. Population density was nominally negatively associated
      with height for foreign-born Mexican-American females. Our findings reveal that
      lower physical stature for some ethnic and gender groups is clustered within
      neighborhoods of low SES and education, suggesting that contextual factors may
      play a role in influencing height above individual-level attributes.

PMID- 22613510
TI  - Improved correlation between CT emphysema quantification and pulmonary function
      test by density correction of volumetric CT data based on air and aortic density.
AB  - OBJECTIVES: To determine the improvement of emphysema quantification with density
      correction and to determine the optimal site to use for air density correction on
      volumetric computed tomography (CT). METHODS: Seventy-eight CT scans of COPD
      patients (GOLD II-IV, smoking history 39.2+/-25.3 pack-years) were obtained from
      several single-vendor 16-MDCT scanners. After density measurement of aorta,
      tracheal- and external air, volumetric CT density correction was conducted (two
      reference values: air, -1,000 HU/blood, +50 HU). Using in-house software,
      emphysema index (EI) and mean lung density (MLD) were calculated. Differences in
      air densities, MLD and EI prior to and after density correction were evaluated
      (paired t-test). Correlation between those parameters and FEV1 and FEV1/FVC were
      compared (age- and sex adjusted partial correlation analysis). RESULTS: Measured
      densities (HU) of tracheal- and external air differed significantly (-990 +/- 14,
      -1016 +/- 9, P<0.001). MLD and EI on original CT data, after density correction
      using tracheal- and external air also differed significantly (MLD: -874.9 +/-
      27.6 vs. -882.3 +/- 24.9 vs. -860.5 +/- 26.6; EI: 16.8 +/- 13.4 vs. 21.1 +/- 14.5
      vs. 9.7 +/- 10.5, respectively, P<0.001). The correlation coefficients between CT
      quantification indices and FEV1, and FEV1/FVC increased after density correction.
      The tracheal air correction showed better results than the external air
      correction. CONCLUSION: Density correction of volumetric CT data can improve
      correlations of emphysema quantification and PFT.

PMID- 22613512
TI  - Sociality of an agent during morphogenetic canalization: asynchronous updating
      with potential resonance.
AB  - Canalization is a typical self-organization process leading to complementarity
      between parts and the whole. In the field of developmental biology, concerns
      about morphogenesis canalization are often framed as the French flag problem,
      questioning how each cell knows its own position in the whole system. Although
      chemical gradients have been suggested to provide positional information, there
      is no direct evidence that gradients are used to gain positional information. The
      chemical gradient hypothesis is based on the assumption that agents (e.g., cells)
      in a domain that locally interact with each other can generate a chemical
      gradient thanks to a global reference point. Instead of a chemical gradient, we
      here propose a model based on agents that are equipped with sociality that is
      based not on a global reference but rather on the ability to sense other
      neighboring agents, or potential resonance. The interaction among the agents with
      sociality, developed from undifferentiated types or tokens, is implemented using
      asynchronous updating automata equipped with potential resonance. We show that
      these automata can generate a French flag pattern that is very robust against
      perturbations without positional information by comparing automata with
      synchronous updating and asynchronous automata without potential resonance.

PMID- 22613514
TI  - Domestic coronary drug-eluting stents on a new horizon.

PMID- 22613513
TI  - Morphogenesis of active shells.
AB  - We consider the active shell as a single-cell or epithelial sheet surface that,
      sharing basic properties of stretched elastic shells, is capable of active planar
      movement owing to recruiting of the new surface elements. As model examples of
      their morphogenesis, we consider the growth and differentiation of single-cell
      hairs (trichomes) in plants of the genus Draba, and the epiboly and formation of
      the dorsoventral polarity in loach. The essential feature of the active shell
      behavior at both cellular and supracellular levels is regular deviating from the
      spatially homogeneous form, which is a primary cause of originating of the active
      mechanical stresses inside the shell in addition to its passive stretching by the
      intrinsic forces. Analyzing the quantitative morphological data, we derive the
      equations in which the temporal self-oscillations and spatial differentiation are
      distinguishable only at the parametric level depending on the proportion of
      active to passive stresses. In contrast to the ordinary activator-inhibitor
      systems, the self-oscillation dynamics is principally non-local and,
      consequently, one-parametric, the shell surface curvature being an analog of the
      inhibitor, while its spatial variance being an analog of the activator of
      shaping. Analyzing variability and evolution of the hair cell branching, we argue
      that the linear ontogeny (succession of the developmental stages) is a secondary
      evolutionary phenomenon originating from cyclic self-organizing algorithms of the
      active shell shaping.

PMID- 22613515
TI  - Preinfarction angina: old story initiates new attention.

PMID- 22613516
TI  - First report of a novel abluminal groove filled biodegradable polymer rapamycin
      eluting stent in de novo coronary artery disease: results of the first in man
      FIREHAWK trial.
AB  - BACKGROUND: Durable polymers used for first-generation drug-eluting stents (DES)
      potentially contribute to persistent inflammation and late DES thrombosis. We
      report the first in human experience with the rapamycin-eluting biodegradable
      polymer coated cobalt-chromium FIREHAWK stent with abluminal groove. METHODS: A
      total of 21 patients with stable or unstable angina, or prior myocardial
      infarction, with single de novo native coronary stenoses < 30 mm in length in
      vessel sizes ranging from 2.25 to 4.0 mm were enrolled. The primary endpoint was
      major adverse cardiac events (MACE) at 30 days defined as the composite of
      cardiac death, myocardial infarction (Q and non-Q), or ischemia-driven target
      lesion revascularization. Secondary endpoints include device, lesion, and
      clinical success rates, 4-month in-stent late lumen loss by quantitative coronary
      angiography (QCA), proportion of uncovered or malapposed stent struts by optical
      coherence tomograpphy (OCT) at 4 months, and MACE at 4, 12, 24 and 36-month
      follow-up. RESULTS: Device success was 95.7%, lesion and clinical success was
      100.0%. There were no MACE events at 30 days. One patient died of non-cardiac
      hemorrhagic stroke 5 days after index procedure. At 4 months, in-stent late loss
      was (0.13 +/- 0.18) mm, and complete strut coverage was 96.2% by OCT with 0.1%
      strut malapposition. At 4-month follow-up there was no additional MACE events,
      and a single target vessel (non-target lesion) revascularization. CONCLUSIONS:
      The FIREHAWK abluminal groove biodegradable polymer rapamycin-eluting stent
      demonstrated feasibility, safety and efficacy in this first in human experience.
      OCT findings indicated excellent stent strut coverage 4 months after
      implantation. Larger studies are required to confirm whether the early FIREHAWK
      stent results translate into longer term restenosis and thrombosis benefits.

PMID- 22613517
TI  - Impact of angina prior to acute ST-elevation myocardial infarction on short-term
      outcomes after primary percutaneous coronary intervention: results from the
      Shanghai Registry of Acute Coronary Syndrome (SRACE).
AB  - BACKGROUND: The clinical significance of ischemic chest pain before acute ST
      elevation myocardial infarction (STEMI) remains an interesting issue of
      investigation particularly in the era of percutaneous coronary intervention
      (PCI). This study aimed to assess the impact of angina prior to STEMI on short
      term clinical outcomes in patients with acute STEMI undergoing primary PCI.
      METHODS: Among a total of 875 consecutive patients with STEMI undergoing primary
      PCI, 292 had episodes of angina within 24 hours of STEMI (PA group) and the
      remaining 583 were free of anginal symptoms (non-PA group). Clinical
      characteristics, angiographic and procedural features, and in-hospital and 30-day
      outcomes were compared between the two groups. RESULTS: Diabetes was less common
      (17.5% vs. 23.3%, P = 0.04) and symptom-to-door time was shortened ((191.6 +/-
      96.8) minutes vs. (357.2 +/- 341.9) minutes, P < 0.001) in the PA group than in
      the non-PA group. Patients with angina prior to STEMI had fewer totally or nearly
      totally occluded infarct-related artery (TIMI flow grade 0 - 1) at initial
      angiography (75.0% vs. 90.7%, P < 0.001), and achieved more TIMI flow grade 3
      after primary PCI (84.2% vs. 78.2%, P = 0.04). These were associated with higher
      rates of overall procedural success (95.9% vs. 91.8%, P = 0.02) and of complete
      ST-segment resolution at 90 minutes after the procedure (51.7% vs. 40.3%, P =
      0.001). During a 30-day clinical follow-up, the left ventricular ejection
      fraction was significantly improved ((53.0 +/- 8.6)% vs. (51.1 +/- 9.7)%, P =
      0.002) and the primary endpoint of major adverse cardiac events was reduced in
      the PA group (7.2% vs. 12.7%, P = 0.01). CONCLUSION: Presence of angina prior to
      acute STEMI is associated with better outcome at a 30-day clinical follow-up in
      patients undergoing primary PCI.

PMID- 22613518
TI  - Safety and efficacy of cobalt chromium alloy based sirolimus-eluting stent with
      bioabsorbable polymer in porcine model.
AB  - BACKGROUND: First generation drug-eluting stents (DESs) were based on 316L
      stainless steel and coated with a permanent polymer. The vessel wall of these
      DESs was inflammatory and late in-stent thrombosis was reported. Hence, cobalt
      chromium based DES coated with a bioabsorbable polymer was an alternate choice.
      METHODS: Cobalt chromium based DES with bioabsorbable polymer (Simrex stent) as
      well as control stents (Polymer stent and EXCEL(TM) stent) were implanted into
      porcine arteries. At a designated time, angiography, quantitative coronary
      angiography (QCA) analysis, histomorphometry, and electron-microscopical follow
      up were performed. RESULTS: A total of 98 stents of all the three groups were
      harvested. At week 24, percent diameter stenosis (%DS), late loss (LL), and
      percent area stenosis (%AS) of Simrex was (12.9 +/- 0.4)%, (0.35 +/- 0.02) mm,
      and (24.5 +/- 4.2)%, respectively, without significant difference in comparison
      to commercialized EXCEL(TM) stent. Slight inflammatory reaction was seen around
      the stent strut of Simrex, just as in the other two groups. Electron
      microscopical follow-up suggested that it might take 4 - 12 weeks for Simrex to
      complete its re-endothelialization process. CONCLUSIONS: Cobalt chromium based,
      bioabsorbable polymer coated sirolimus-eluting stent showed excellent
      biocompatibility. During 24 weeks observation in porcine model, it was proved
      that this novel DES system successfully inhibited neointima hyperplasia and
      decreased in-stent stenosis. It is feasible to launch a clinical evaluation to
      improve the current prognosis of DES implantation.

PMID- 22613519
TI  - Improvement of P-wave dispersion is associated with a lower incidence of atrial
      fibrillation after cardiac resynchronization therapy.
AB  - BACKGROUND: P-wave dispersion (PWD) is a useful predictor of paroxysmal atrial
      fibrillation (AF). The effect of cardiac resynchronization therapy (CRT) on PWD
      and the prognostic implications of the improvement in PWD remain undefined. The
      aim of the study was to explore the clinical significance of the improvement of
      PWD after CRT. METHODS: Electrocardiographic studies were performed before and
      three months after CRT in 81 patients (57 men and 24 women; age (60.5 +/- 11.2)
      years) with standard CRT indication but no history of AF. A significant
      improvement of PWD (PWD responder) was defined as a relative decrease >= 20% from
      baseline PWD. The primary endpoints were new-onset AF detected by
      electrocardiogram (ECG) or CRT. RESULTS: After (30.6 +/- 7.5) months of follow
      up, PWD responders (n = 43) had a significantly lower incidence of AF than did
      PWD nonresponders, 12% vs. 29% (P < 0.001). In Cox proportional hazard analysis,
      PWD responders was the only predictor of lower risk of new-onset AF (HR 0.33, 95%
      confidence interval 0.12 - 0.96, P = 0.033). CONCLUSION: Improvement of P-wave
      dispersion after CRT was associated with a lower incidence of AF, which may be
      related to the significant improvement in left ventricular systolic function and
      the reverse modeling of the left atrium.

PMID- 22613520
TI  - Novel miniature mobile cardiac catheterization laboratory for critical
      cardiovascular disease following natural disasters: a feasibility study.
AB  - BACKGROUND: Natural disasters have been frequent in recent years. Effective
      treatment of patients with cardiovascular disease following natural disasters is
      an unsolved problem. We aimed to develop a novel miniature mobile cardiac
      catheterization laboratory (Mini Mobile Cath Lab) to provide emergency
      interventional services for patients with critical cardiovascular disease
      following natural disasters. A feasibility study was performed by testing the
      Mini Mobile Cath Lab on dogs with ST-elevation myocardial infarction (STEMI)
      model in a hypothetical natural-disaster-stricken area. METHODS: The Mini Mobile
      Cath Lab was transported to the hypothetical natural-disaster-stricken area by
      truck. Coronary angiography and primary percutaneous coronary intervention (PCI)
      were performed on six dogs with STEMI model. The transportation and
      transformation of the Mini Mobile Cath Lab were monitored and its functioning was
      evaluated through the results of animal experiments. RESULTS: The Mini Mobile
      Cath Lab could be transported by truck at an average speed of 80 km/h on mountain
      roads during daytime in the winter, under conditions of light snow (-15 degrees C
      to -20 degrees C/-68 degrees F to -59 degrees F). The average time required to
      prepare the Mini Mobile Cath Lab after transportation, in a wetland area, was 30
      minutes. Coronary angiography, and primary PCI were performed successfully.
      CONCLUSION: This preliminary feasibility study of the use of the Mini Mobile Cath
      Lab for emergency interventional treatment of dogs with STEMI indicated that it
      may perform well in the rescue of critical cardiovascular disease following
      natural disasters.

PMID- 22613521
TI  - Coronary stenting versus bypass surgery in heart failure patients with preserved
      ejection fraction.
AB  - BACKGROUND: The optimal revascularization strategy in patients with heart failure
      with preserved ejection fraction (HFPEF) remains unclear. The aim of the present
      study was to compare the effects of percutaneous coronary intervention (PCI) and
      coronary artery bypass grafting (CABG) in patients with HFPEF. METHODS: From July
      2003 through September 2005, a total of 920 patients with coronary artery disease
      (CAD) and HFPEF (ejection fraction >= 50%) underwent PCI (n = 350) or CABG (n =
      570). We compared the groups with respect to the primary outcome of mortality,
      and the secondary outcomes of main adverse cardiac and cerebral vascular events
      (MACCE), including death, myocardial infarction, stroke and repeat
      revascularization, at a median follow-up of 543 days. RESULTS: In-hospital
      mortality was significantly lower in the PCI group than in the CABG group (0.3%
      vs. 2.5%, adjusted P = 0.016). During follow-up, there was no significant
      difference in the two groups with regard to mortality rates (2.3% vs. 3.5%,
      adjusted P = 0.423). Patients receiving PCI had higher MACCE rates as compared
      with patients receiving CABG (13.4% vs. 4.0%, adjusted P < 0.001), mainly due to
      higher rate of repeat revascularization (adjusted P < 0.001). Independent
      predictors of mortality were age, New York Heart Association (NYHA) class and
      chronic total occlusion. CONCLUSION: Among patients with CAD and HFPEF, PCI was
      shown to be as good as CABG with respect to the mortality rate, although there
      was a higher rate of repeat revascularization in patients undergoing PCI.

PMID- 22613522
TI  - Use of covered Cheatham-Platinum stent as the primary modality in the treatment
      for native coarctation of the aorta.
AB  - BACKGROUND: Bare stent implantation in the treatment for native and recurrent
      coarctation of the aorta (CoA) has become established as an alternative to
      surgery and balloon angioplasty. However, this modality still encounters
      significant complications during the procedure and/or follow-up. The covered
      Cheatham-Platinum (CP) stent commonly used to be chosen as a rescue treatment in
      these patients. The purpose of this study was to evaluate the use of covered CP
      stent as the primary modality in the treatment for native CoA. METHODS: Twenty
      five covered CP stents and 2 bare CP stents were implanted in 25 patients with
      native CoA. All patients after the intervention were invited for follow-up
      examinations. RESULTS: The peak systolic gradient across the lesion decreased
      significantly from a median value of 67.5 mmHg (quartile range, 19.3 mmHg) to 2
      mmHg (quartile range, 4.0 mmHg) (P < 0.0001). Stenotic segment diameter increased
      from a median value of 5.0 mm (quartile range, 1.5 mm) to 17.9 mm (quartile
      range, 2.5 mm) (P < 0.0001). The median ratio of diameter of the coarctation
      postprocedure to preprocedure was 4.2 (quartile range, 1.6). All of the CP stents
      were placed in the suitable position without any acute complications. During a
      follow-up period of up to 72 months, no complications were encountered. Most of
      the patients (21/25) were normotensive, apart from four patients requiring
      antihypertensive medication during the follow-up. CONCLUSION: The implantation of
      covered CP stent as the primary modality is safe and effective in the treatment
      for native CoA in adolescents and adults.

PMID- 22613523
TI  - Comparison of the safety of simultaneous bilateral carotid artery stenting versus
      unilateral carotid artery stenting: 30-day and 6-month results.
AB  - BACKGROUND: Severe bilateral carotid stenosis caused by atherosclerosis has not
      been unusual in the elderly. Such patients have high stroke risk. Many studies
      show that carotid artery stenting (CAS) is an alternative to treat unilateral
      carotid stenosis. However, the optimal procedural strategy of bilateral carotid
      stenosis remains unclear. The purpose of our study was to evaluate the safety of
      simultaneous bilateral carotid artery stenting (SBCAS) compared with unilateral
      carotid artery stenting (UCAS). METHODS: In this single-center retrospective
      study, we analyzed 234 consecutive patients who underwent carotid stenting from
      January 2005 to December 2009. Thirty-nine patients (16.7%) of them underwent
      SBCAS, and the others (n = 195) underwent UCAS. Indication for CAS was defined as
      carotid artery diameter reduction > 60% (symptomatic) or > 80% (asymptomatic).
      Six-month and 30-day hemodynamic depression (HD), hyperperfusion syndrome (HPS),
      stroke, death and myocardial infarction (MI) after carotid stenting were
      assessed. RESULTS: SBCAS group had no more HD and HPS compared with UCAS group at
      30 days (HD: 28.2% vs. 20.0%, P = 0.396; HPS: 2.6% vs. 2.1%, P = 0.262).
      Moreover, there was no statistically significant difference between SBCAS group
      and UCAS group in major stroke, death, MI and their combinations within 30 days
      (major stroke: 0 vs. 3.6%, P = 0.604; death: 2.6% vs. 1.5%, P = 0.520; MI: 2.6%
      vs. 0.5%, P = 0.306; and their combinations: 5.1% vs. 4.6%, P = 1.000) and 6
      months (major stroke: 0 vs. 3.6%, P = 0.604; death: 5.1% vs. 2.1%, P = 0.262; MI:
      5.1% vs.1.0%, P = 0.130 and their combinations: 7.7% vs. 5.1%, P = 0.459).
      CONCLUSIONS: The patients undergoing SBCAS had no more events than those
      undergoing UCAS in 30-day and 6-month follow-up. Our finding suggests that SBCAS
      appears to be as safe as UCAS.

PMID- 22613525
TI  - Predictive value of postprocedural leukocyte count on myocardial perfusion, left
      ventricular function and clinical outcomes in ST-elevated myocardial infarction
      after percutaneous coronary intervention.
AB  - BACKGROUND: Baseline white blood cell (WBC) count was correlated with ischemic
      events occurrence in patients with ST-elevated myocardial infarction (STEMI).
      However, circulating WBC count is altered after percutaneous coronary
      intervention (PCI). The aim of this study was to assess the relationship between
      postprocedural WBC count and clinical outcomes in STEMI patients who underwent
      PCI. METHODS: A total of 242 consecutive acute STEMI patients who underwent
      successful primary PCI were enrolled and followed up for two years. WBC counts
      were measured within 12 hours after PCI. ST-segment resolution (ST-R) and
      myocardial blush grades (MBG) were evaluated immediately after PCI. Left
      ventricular ejection fraction (LVEF) was obtained at baseline and 12 - 18 months
      after PCI. RESULTS: Postprocedural WBC count was an independent inverse predictor
      of ST-R (OR 0.80, P < 0.0001) and MBG 3 (OR 0.82, P < 0.0001). It was negatively
      correlated with LVEF (baseline r = -0.22, P = 0.001; 12 - 18 months r = -0.29, P
      < 0.0001). The best cutoff value of WBC for predicting death was determined to be
      13.0 * 10(9)/L. The patients with a postprocedural WBC count above 13.0 * 10(9)/L
      showed a significantly lower cumulative survival rate (30 days, 82.4% vs. 99.0%,
      P < 0.0001 and 2 years 75.0% vs. 96.4%, P < 0.0001). Multivariate Cox regression
      analysis showed that a postprocedural WBC count was a strong independent
      predictor of 30-day mortality (HR 8.48, P = 0.019) and 2-year mortality (HR 4.93,
      P = 0.009). CONCLUSIONS: Increased postprocedural WBC count is correlated with
      myocardial malperfusion and left ventricular dysfunction, and is an independent
      predictor of poor clinical outcomes in STEMI patients who underwent PCI.

PMID- 22613524
TI  - Randomized study on the safety and efficacy of dual-axis rotational versus
      standard coronary angiography in.
AB  - BACKGROUND: Dual-axis rotational coronary angiography (DARCA) was developed as an
      innovative adaptation of rotational angiography (RA), but it requires a longer
      coronary injection compared to standard coronary angiography (SA). As the body of
      the average Chinese patient is smaller than that of most western patients, with
      the same contrast injection time, the risk of complications from the contrast
      agent is increased in this population. The purpose of this study was to assess
      the clinical safety and efficacy of DARCA in the diagnosis of coronary artery
      disease (CAD) in the Chinese population by directly comparing it to SA. METHODS:
      Two hundred Chinese patients were randomized to either the SA group (n = 100) or
      DARCA group (n = 100). Contrast utilization, radiation exposure and procedure
      time were recorded for each modalities. Blood pressure (BP), heart rate (HR) pre
      and post injection symptoms and any arrhythmias were recorded. RESULTS: Compared
      to the SA group, there was a 42% reduction in contrast utilization, 55% reduction
      in radiation exposure and a 31% shorter procedure time in the DARCA group. In
      both groups, there were slight declines in the systolic BP values in the left
      coronary artery (LCA) post injection (P < 0.01). Moreover, post injection HRs for
      the LCA were also reduced in the DARCA group (P < 0.01). But all of these changes
      were small, transient and without clinical importance. Only one patient (1%) in
      the DARCA group had an attack of ventricular tachycardia immediately post
      injection and it resolved by itself during LCA angiography. No arrhythmias
      occurred in the SA group. CONCLUSION: DARCA is a safe, efficient, and clinically
      comparable alternative to SA in the diagnosis of coronary artery disease in the
      Chinese population with less contrast utilized, which is less radiation exposure
      and a shorter procedure time than SA.

PMID- 22613526
TI  - Severe coronary artery disease in Chinese patients with abdominal aortic
      aneurysm: prevalence and impact on operative mortality.
AB  - BACKGROUND: Little is known about the prognosis of coronary artery disease (CAD)
      in Chinese patients with abdominal aortic aneurysm (AAA). The aim of this study
      was to evaluate the predictors of in-hospital all-cause mortality of severe CAD
      in Chinese patients who were hospitalized for AAAs. METHODS: From January 2003 to
      August 2009, 368 patients were operated on for AAAs. The clinical characteristics
      were retrospectively collected. The primary outcome was the in-hospital all-cause
      mortality. The clinical risk factors were subjected to a multivariate analysis to
      determine the predictors of in-hospital all-cause mortality. RESULTS: During
      their hospitalization, 23% (85/368) of the patients underwent coronary
      angiography, which revealed significant lesions in 93% (79/85) of the patients.
      In 25 cases, coronary artery bypass grafting (CABG) was performed before the AAA
      repair and in 16 cases of percutaneous coronary intervention (PCI) was performed.
      Ten patients with AAA alone died before discharge, and eight patients diagnosed
      with AAA combined with CAD died. There was no statistical difference in the
      postoperative death between the two groups. The logistic analysis showed that age
      > 70 years and CAD (vessels >= 2) were the significant factors in predicting the
      adverse clinical outcome. CONCLUSIONS: The prevalence of severe CAD in Chinese
      patients with AAAs seemed lower than those that were reported. Myocardial
      evaluation and subsequent revascularization before AAA surgery could improve the
      clinical outcome for these patients who have severe CAD.

PMID- 22613528
TI  - Impact of weight gain following smoking cessation on one-year outcome after drug
      eluting stent implantation.
AB  - BACKGROUND: Weight gain following smoking cessation increases cardiovascular
      risk, but its effects on prognosis after percutaneous coronary intervention (PCI)
      remain unclear. This study aimed to investigate the relationship between weight
      gain post smoking cessation and one-year clinical outcome in patients who
      underwent PCI with drug-eluting stent (DES). METHODS: A total of 895 consecutive
      male smoking patients were divided into quitters (n = 437) and continuers (n =
      458) according to their smoking status after PCI. Weight gain, major adverse
      cardiac events (MACE, including cardiac deaths, myocardial infarction and
      revascularization), and recurrent angina were recorded during follow-up for one
      year. RESULTS: Average weight gain in quitters was more than that in continuers
      (1.5 kg vs. -0.03 kg, P < 0.001). Weight was unchanged or increased by more than
      1.5 kg in 78.17% of continuers, while 50.57% of quitters had a weight gain of
      less than 1.5 kg. Compared with continuers, MACE in quitters was significantly
      reduced after PCI (6.12% vs. 4.81%, P = 0.049), especially recurrent angina
      (13.97% in continuers vs. 9.84% in quitters, P = 0.027). After adjusting for
      weight gain and other factors, smoking cessation was independently associated
      with a lower risk of MACE and recurrent angina (OR = 0.73, P = 0.035). However,
      weight gain > 1.5 kg (OR = 1.55, P = 0.026) could curtail the benefits from
      smoking cessation. CONCLUSIONS: Weight gain may reduce the benefits of smoking
      cessation after PCI with DES implantation. Thus, although smoking cessation is
      recommended after PCI, weight control should also be highly encouraged for these
      patients.

PMID- 22613527
TI  - Clinical outcomes after recanalization of a chronic total occluded vessel with
      bifurcation lesions: results from single-center, prospective, chronic total
      occlusion registry study.
AB  - BACKGROUND: Stenting strategies and clinical outcomes of bifurcation lesions in a
      chronic total occlusion (CTO) vessel after successful recanalization remain to be
      unknown. METHODS: Between January 2001 and December 2009, 195 (41.1%) patients
      with 254 (47.0%) bifurcation lesions in CTO vessels from a pool of 564 patients
      with 659 CTO lesions were included and divided into proximal (n = 134) and distal
      (n = 120) groups, according to the location of the bifurcation lesions. The
      primary endpoint was the occurrence of major adverse cardiac events (MACE) at the
      end of clinical follow-up, including cardiac death, myocardial infarction, or
      target vessel revascularization (TVR). RESULTS: Collaterals with Rentrop class 3
      were seen more in distal group (100% and 68.3%), compared to proximal group
      (76.9% and 45.6%). Two-stent technique for proximal bifurcation lesions was used
      in 24.6%, significantly different from the distal group (6.7%, P < 0.001),
      without significant difference in composite MACE between proximal and distal
      groups, or between one- and two-stent subgroups in proximal group. The composite
      MACE after 1-year in complete revascularization subgroup was 17.9% relative to
      29.6% in the incomplete revascularization group (P = 0.044). Stents in long false
      lumen in main vessel were mainly attributive to decreased TIMI grade flow, with
      resultant increased in-stent restenosis, total occlusion, TVR and coronary
      aneurysms. Imcomplete revasculzarization (HR 2.028, P = 0.049, 95%CI 1.002 -
      4.105) and post-stenting TIMI flow (HR 6.122, P = 0.020, 95%CI 1.334 - 28.092)
      were two independent predictors of composite MACE at the 1-year follow-up.
      CONCLUSIONS: Two-stent was more used for proximal bifurcation lesions. No
      significant difference was observed in MACE between proximal and distal, or
      between one- and two-stent subgroups in the proximal group. Placement of a safety
      wire was critical for proximal bifurcation lesions. Complete revascularization
      was mandatory to improve clinical outcomes.

PMID- 22613529
TI  - Optical coherence tomography assessment of edge dissections after drug-eluting
      stent implantation in coronary artery.
AB  - BACKGROUND: Edge dissections after coronary stent implantation are associated
      with increased short-term risk of major adverse cardiovascular events. The
      incidence and outcome of edge dissections after coronary stent implantation were
      reportedly different using different imaging techniques. We used optical
      coherence tomography (OCT) to assess the incidence, morphological findings and
      related factors of edge dissections after drug-eluting stent (DES) implantation.
      METHODS: Totally 42 patients with 43 de novo lesions in 43 native arteries
      undergoing DES implantation with OCT imaging were enrolled in this study.
      RESULTS: Nine edge dissections were detected in 43 arteries after DES
      implantation. There were four morphological patterns of stent edge dissections
      indentified in this study: (1) superficial intimal tears (n = 3), (2) subintimal
      dissections (n = 4), (3) split of media (n = 1), (4) disruption of the fibrotic
      cap of plaque (n = 1). Stent edge expansion and stent expansion were both higher
      in the group with dissections than those in the group without dissections (1.682
      +/- 0.425 vs. 1.229 +/- 0.285, P = 0.0290; 1.507 +/- 0.445 vs. 1.174 +/- 0.265, P
      = 0.0072). CONCLUSIONS: The incidence of stent edge dissections detected by OCT
      was 21%. Stent edge dissection is related with stent edge expansion and stent
      expansion.

PMID- 22613530
TI  - Plasma neutrophil-gelatinase-associated lipocalin and cystatin C could early
      diagnose contrast-induced acute kidney injury in patients with renal
      insufficiency undergoing an elective percutaneous coronary intervention.
AB  - BACKGROUND: Contrast induced acute kidney injury (CIAKI) is an important
      complication in the use of iodinated contrast media (CM). Our study was to
      evaluate the neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C for
      early diagnosis of CIAKI. METHODS: The patients with established or suspected
      coronary artery disease (CAD) with the estimated glomerular filtration rate
      (eGFR) was more than 30 ml * min(-1) * 1.73 m(-2) and nor more than 90 ml * min(
      1)* 1.73 m(-2) were continuously enrolled. The blood samples of the first 50
      patients were obtained before and at 2, 4, 8, 24 and 48 hours after procedure to
      identify the time points at which the biomarkers reached peaks and at which the
      blood samples of the rest of patients were obtained. The plasma NGAL and cystatin
      C measure used enzyme-linked immunosorbent assay (ELISA) kit. The diagnostic
      characteristics of absolute and relative increasing NGAL and cystatin C for CIAKI
      were evaluated. RESULTS: Total 311 patients were enrolled, among whom 39 (12.5%)
      developed CIAKI. Plasma NGAL increased at 2 hours and reached peak at 4 hours
      after procedure, while plasma cystatin C increased at 2 hours and reached peak at
      24 hours after procedure. Thus, we determine rational point of time at 4 hours
      for NGAL and at 24 hours after procedure for cystatin C, respectively. The plasma
      NGAL at 4 hours after CM exposure showed largest area under curve (AUC) of 0.662
      (95% confidence interval (CI): 0.565 - 0.758, P = 0.002) with 51.5% sensitivity
      and 80.6% of specificity. The relative increasing 25% of NGAL showed the best
      sensitivity and specificity of 0.872 and 0.808, respectively, with maximum Youden
      index of 0.680, while cystatin C with relative increasing more than 25% had 76.9%
      of sensitivity and 81.2% of specificity. Combined two biomarkers might get more
      than 90% of specificity. CONCLUSIONS: Single measurement of NGAL or cystatin C
      had poor sensitivity and specificity; however, the relative increasing 25% of
      NGAL at 4 hours after CM exposure demonstrated higher diagnostic values for
      CIAKI. Combining relative increasing plasma NGAL with relative increasing plasma
      cystatin C might perform better for early diagnosis of CIAKI.

PMID- 22613531
TI  - Defective T wave combined with incomplete right bundle branch block: a new
      electrocardiographic index for diagnosing atrial septal defect.
AB  - BACKGROUND: Incomplete right bundle branch block (ICRBBB) is commonly associated
      with atrial septal defect (ASD), but lacks sufficient diagnostic test
      characteristics. An abnormal T wave is also often observed in ASD, with
      horizontal or inverted displacement of the proximal T wave limb in the right
      precordial leads, termed "defective T wave" (DTW). METHODS: We examined the
      diagnostic test characteristics of combining ICRBBB with DTW as a new index to
      diagnose ASD. A total of 132 consecutive patients with ASD and 132 cases of
      age/gender-matched controls without ASD were enrolled. RESULTS: Sensitivities of
      DTW, ICRBBB, and both were 87.1% - 87.9%. Specificities were 97.0%, 96.2%, and
      100%, respectively. Positive predictive values were 1.3%, 1.1%, and 100.0%
      respectively, while negative predictive values were 99.9% for each. CONCLUSION:
      Combining ICRBBB with DTW in electrocardiogram (ECG) as a new index significantly
      increased the specificity and positive predictive values while maintaining a high
      sensitivity in diagnosing ASD.

PMID- 22613532
TI  - Safety and efficacy of anisodamine on prevention of contrast induced nephropathy
      in patients with acute coronary syndrome.
AB  - BACKGROUND: Previous studies have proved the renal protective effects of
      anisodamine in patients with septic shock. The aim of this study was to
      investigate anisodamine for the prevention of contrast induced nephropathy (CIN)
      in patients with acute coronary syndrome (ACS). METHODS: Consecutive ACS patients
      undergoing elective percutaneous coronary intervention (PCI) were randomly
      assigned to one of two groups: patients in the anisodamine group (ANI group) were
      assigned to receive intravenous infusions of anisodamine by an adjusted-dose (0.1
      - 0.2 ug * kg(-1)* min(-1)) from the PCI procedure to 24 hours after PCI, and the
      control group (CON group) received 0.9% isotonic saline of the same volume. All
      patients were hydrated for 6 to 12 hours before and 12 hours after PCI. Blood
      samples were taken on the day of PCI and at 24, 48 and 72 hours after PCI to
      measure the serum creatinine (SCr). RESULTS: A total of 177 patients were
      involved in the study, 88 in the ANI group and 89 in the CON group. In both
      groups, the SCr concentrations significantly increased after PCI, with the peak
      value occurring at 48 hours. At 72 hours, the SCr concentration in the ANI group
      retuned to the baseline level (P > 0.05), but the SCr concentration in CON group
      was still higher than baseline level (P < 0.01). The SCr concentrations at 48 and
      72 hours after PCI were much lower in the ANI group than those in the CON group
      (both P < 0.01). The estimated glomerular filtration rate (eGFR) significantly
      decreased after PCI, the lowest value occurred at 48 hours. In the ANI group, the
      eGFR at 72 hours was similar to the baseline level. In the CON group, the eGFR
      failed to return to baseline at 72 hours (P < 0.01). The eGFR at 24, 48 and 72
      hours after PCI were higher in the ANI group (all P < 0.05). The incidence of CIN
      in the ANI group was lower than that in the CON group within 72 hours after PCI
      (P < 0.05). The results of multiple Logistic regression proved that both diabetes
      and left ventricular ejection fraction (LVEF) were independent predictors of CIN,
      and treatment with anisodamine was an independent preventive factor of CIN (OR
      0.369 and 95%CI 0.171 to 0.794, P = 0.011). No serious side effects were found in
      the ANI group. CONCLUSION: Intravenous infusion of anisodamine during and after
      elective PCI may safely prevent the occurrence of CIN in ACS patients.

PMID- 22613533
TI  - Frequency- and state-dependent blockade of human ether-a-go-go-related gene K+
      channel by arecoline hydrobromide.
AB  - BACKGROUND: The rapidly activating delayed rectifier potassium current (I(Kr)),
      whose pore-forming alpha subunit is encoded by the human ether-a-go-go-related
      gene (hERG), is a key contributor to the third phase of action potential
      repolarization. The aim of this study was to investigate the effect and mechanism
      of arecoline hydrobromide induced inhibition of hERG K(+) current (I(hERG)).
      METHODS: Transient transfection of hERG channel cDNA plasmid pcDNA3.1 into the
      cultured HEK293 cells was performed using Lipofectamine. A standard whole-cell
      patch-clamp technique was used to record the I(hERG) before and after the
      exposure to arecoline. RESULTS: Arecoline decreased the amplitude and the density
      of the I(hERG) in a concentration-dependent manner (IC(50) = 9.55 mmol/L). At
      test potential of +60 mV, the magnitude of I(hERG) tail at test pulse of -40 mV
      was reduced from (151.7 +/- 6.2) pA/pF to (84.4 +/- 7.6) pA/pF (P < 0.01, n = 20)
      and the magnitude of I(hERG) tail at test pulse of -110 mV was reduced from (
      187.5 +/- 9.8) pA/pF to (-97.6 +/- 12.6) pA/pF (P < 0.01, n = 20). The blockade
      of arecoline in the open and inactivated state was significant in a state
      dependent manner. The maximal blockade was achieved in the inactivated state.
      Studies of gating mechanism showed that the steady-state activation curve of
      I(hERG) was significantly negatively shifted by arecoline. Time constants of
      activation were shortened. Steady-state inactivation curve and time constants of
      fast inactivation were not significantly affected by arecoline. Furthermore, the
      inhibition of I(hERG) by arecoline was characterized markedly by a frequency
      dependent manner from 0.03 to 1.00 Hz pulse. CONCLUSION: Arecoline could potently
      block I(hERG) in both frequency and state-dependent manner.

PMID- 22613535
TI  - Clinical efficacy of three different minimally invasive procedures for far
      lateral lumbar disc herniation.
AB  - BACKGROUND: Far lateral lumbar disc herniation (FLLDH) accounts for 2.6% to 11.7%
      of all lumbar herniated discs. Numerous surgical approaches have been described
      for treating this condition. The purpose of this study was to evaluate minimally
      invasive surgical techniques for the treatment of FLLDH. METHODS: From June 2000
      to March 2006, 52 patients with FLLDH were treated with minimally invasive
      procedures. All patients were assessed by anteroposterior and lateral
      roentgenography and computed tomography (CT). Some patients underwent
      myelography, discography, and magnetic resonance imaging. Procedures performed
      included Yeung Endoscopy Spine System (YESS) (n = 25), METRx MicroDiscectomy
      System (n = 13), and X-tube (n = 14). Patients were followed up for a mean of
      13.5 months. Clinical outcomes were assessed using a visual analog scale (VAS)
      and Nakai criteria. RESULTS: All 3 procedures significantly improved radiating
      leg symptoms (P < 0.005). After surgery, 84.0%, 84.6%, and 92.8% of patients in
      the YESS, METRx, and X-tube groups had excellent or good outcomes. There were no
      statistically significant differences of VAS scores between the groups. The YESS
      procedure was associated with the shortest operation time, simplest anesthesia,
      and least trauma compared with the other 2 procedures, especially for type I
      herniations. The METRx procedure was the most suitable for type II herniations
      and posterior endoscopic facetectomy. Posterior lumbar interbody fusion and
      unilateral pedicle screw instrumentation with X-tube was the most suitable for
      herniations combined with degenerative lumbar instability (type III). CONCLUSION:
      Minimally invasive strategies and options should be determined with reference to
      the type of FLLDH.

PMID- 22613534
TI  - Genotyping for Kidd, Kell, Duffy, Scianna, and RHCE blood group antigens
      polymorphisms in Jiangsu Chinese Han.
AB  - BACKGROUND: Molecular testing is more precise compared to serology and has been
      widely used in genotyping blood group antigens. Single nucleotide polymorphisms
      (SNPs) of blood group antigens can be determined by the polymerase chain reaction
      with sequence specific priming (PCR-SSP) assay. Commercial high-throughput
      platforms can be expensive and are not approved in China. The genotype
      frequencies of Kidd, Kell, Duffy, Scianna, and RhCE blood group antigens in
      Jiangsu province were unknown. The aim of this study is sought to detect the
      genotype frequencies of Kidd, Kell, Duffy, Scianna, and RhCE antigens in Jiangsu
      Chinese Han using molecular methods with laboratory developed tests. METHODS: DNA
      was extracted from EDTA-anticoagulated blood samples of 146 voluntary blood
      donors collected randomly within one month. Standard serologic assay for red
      blood cell antigens were also performed except the Scianna blood group antigens.
      PCR-SSP was designed to work under one PCR program to identify the following
      SNPs: JK1/JK2, KEL1/KEL2, FYA/FYB, SC1/SC2, C/c and E/e. RESULTS: Serologic
      antigen results were identical to the phenotypes that were predicted from
      genotyping results. The allele frequencies for Jk*01 and Jk*02 were 0.51 and
      0.49, respectively; for Fy*A and Fy*B 0.94 and 0.06; for RHCE*C and RHCE*c 0.68
      and 0.32; and for RHCE*E and RHCE*e 0.28 and 0.72. Among 146 blood donors, all
      were KEL*02/KEL*02 and SC*01/SC*01, indicating allele frequencies for KEL*02 and
      SC*01 close to 1.00. CONCLUSIONS: The use of PCR-SSP working under the same
      condition for testing multiple antigens at the same time is practical. This
      approach can be effective and cost-efficient for small-scale laboratories and in
      developing counties. These molecular tests can be also used for identifying rare
      blood types.

PMID- 22613536
TI  - Pulmonary embolism in adolescents.
AB  - BACKGROUND: Pulmonary embolism (PE) is rare and seldom considered in adolescent
      patients; however it occurs with a greater frequency than is generally
      recognized, and it is a potentially fatal condition. The aim of the current study
      was to understand its epidemiology, clinical features and the cause of delay of
      its diagnosis in adolescents. METHODS: A retrospective analysis of nine
      adolescents with acute PE admitted to the Peking University Third Hospital over
      the past 16-year period was performed. The epidemiology, clinical features and
      risk factors of the adolescents were described and compared with those of adults
      and elderly patients. The time to diagnosis and misdiagnosed diseases were
      analyzed. Pretest probability of PE was assessed retrospectively by the Wells
      score and revised Geneva score. RESULTS: The incidence of PE was 43.6 per 100 000
      hospitalized adolescents in our hospital. The incidence of PE in adolescents was
      much lower than that in adults and PE is diagnosed in about 1/50 of elderly
      people. The clinical features in adolescents were similar to those in adults. But
      fever and chest pain were more common in adolescents (P < 0.05). The major risk
      factors included surgery, systemic lupus erythematosus (SLE), thrombocytopenia,
      long-term oral glucocorticoids and trauma. The mean diagnostic time was (7.8 +/-
      8.4) days. Six cases had a delayed diagnosis. The mean delay time from symptom
      onset to diagnosis was (11.0 +/- 8.8) days. The time of presentation to diagnosis
      in patients initially admitted to the emergency department was less than one day,
      and was much shorter than the time in outpatients, (9.4 +/- 7.5) days. Most of
      the patients were initially misdiagnosed with a respiratory tract infection. Most
      patients' values of Wells score or revised Geneva score were in the moderate or
      high clinical probability categories; 88% by Well score vs. 100% by revised
      Geneva score. CONCLUSIONS: PE was seldom considered in the adolescent patients by
      physicians, especially outpatient physicians, so the diagnosis was often delayed.
      If adolescent patients complain of dyspnea or chest pain or syncope with/without
      fever, and they had risk factors such as surgery, thrombocytopenia and trauma, PE
      should be considered and included in the differential diagnosis.

PMID- 22613537
TI  - Effect of environmental factors on chemoresistance of HepG2 cells by regulating
      hypoxia-inducible factor-1alpha.
AB  - BACKGROUND: Accumulating evidence demonstrates that the microenvironment of the
      host has an important effect on the chemoresistance of tumors. We also found that
      the formation of intrinsic multidrug resistance is related to environmental
      factors that are common with tumor growth of hepatocellular carcinoma. The aim of
      this study was to explore the molecular mechanisms by which multidrug resistance
      of hepatocellular carcinoma is induced by the microenvironment. In particular,
      the regulation of nuclear transcription factor (hypoxia-inducible factor-1alpha,
      HIF-1alpha) activation in the process of multidrug resistance formation was
      investigated. METHODS: HepG2 cells were exposed to different microenvironmental
      conditions respectively, such as hypoxia, stimulation of glucose deprivation and
      transfection of plasmid PcDNA3/HBx. In the HepG2 cells, the expression of the
      related MDR proteins, HIF-1alpha protein expression and localization, activity of
      extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK)
      were detected. Specific inhibitor U0126 was used to block ERK/MAPK signal
      pathway, the alteration of HIF-1alpha and the related MDR proteins were
      investigated. Multivariate analysis of variance (MANOVA) repeated measures and
      one-way analysis of variance (ANOVA) followed by Tukey test or t-test were used
      to determine differences over time and effects of the treatments. RESULTS: The
      above three microenvironment factors increase the expression of the related MDR
      proteins (including P-gp, LRP, and MRP1) and induce MDR of HepG2 cells. HIF
      1alpha was induced at the protein and mRNA levels and the nuclear translocation
      was also increased. The activity of ERK/MAPK was also increased in HepG2 cells.
      But when ERK/MAPK pathway was inhibited, the mRNA and protein expression of MDR1,
      MRP1, and LRP was to some extent decreased. Inhibition of ERK/MAPK significantly
      reduced activated HIF-1alpha protein and the nuclear translocation of HIF-1alpha,
      whereas HIF-1alpha mRNA levels were not affected. CONCLUSIONS: The
      microenvironmental factors could induce MDR of HepG2 cells by the activity of HIF
      1alpha. The activity of HIF-1alpha is regulated by the ERK/MAPK pathway at the
      phosphorylation level. As an important nuclear transcription factor, HIF-1alpha
      controls the transcription of MDR-related genes and the synthesis of their
      corresponding proteins by ERK/MAPK signal pathway in HepG2 cells.

PMID- 22613538
TI  - Clinical and histopathologic features of biofilm-associated chronic
      rhinosinusitis with nasal polyps in Chinese patients.
AB  - BACKGROUND: Biofilms have given new insights to the understanding of pathogenesis
      of chronic rhinosinusitis (CRS). However, the link between biofilms formation and
      local inflammatory response remains poorly defined in CRS with nasal polys. The
      aim of this study was to determine the potential association of the presence of
      biofilms in the nasal mucosal tissues with clinical features in Chinese patients,
      which had CRS with nasal polyps (CRSwNP). METHODS: A total of 19 patients with
      CRSwNP and 12 patients with non-CRS were subjected to endoscopic surgery and
      their nasal mucosal tissue specimens were examined histologically and by scanning
      electron microscopy (SEM). Their demographic and clinical features were recorded.
      RESULTS: Thirteen (68.4%) out of the 19 specimens from patients with CRSwNP, but
      none from control patients, were positive for biofilms that displayed typical
      characteristics of bacterial and fugal structures. The presence of biofilms in
      the nasal mucosal tissues was associated with significantly greater values of
      purulent nasal discharge and preoperative Lund-Kennedy scores, higher levels of
      serum total IgE and percentages of subjects with endoscopic surgery (ESS) history
      in patients with CRSwNP, and more severe inflammation in the nasal mucosal
      tissues of patients with CRSwNP. CONCLUSION: Our study demonstrated the presence
      of biofilms in the nasal mucosal tissues of many patients, contributing to the
      understanding of the pathogenic process of CRSwNP in Chinese patients.

PMID- 22613540
TI  - A clinical neurophysiology study of Hirayama disease.
AB  - BACKGROUND: Hirayama disease is a rare disease characterized by juvenile-onset of
      asymmetric amyotrophy, of which etiology has not been clarified. The aim of our
      study was to investigate the clinical and neurophysiologic characteristics of
      Hirayama disease. METHODS: Neurophysiological tests, including nerve conduction
      studies (NCS), F-wave and routine electromyography (EMG), were performed in
      seventy-three patients with Hirayama disease. EMG was selectively performed on
      upper and lower extremities, sternocleidomast and thoracic paravertebral muscles
      according to the clinical features of the patients. RESULTS: Abnormal NCS
      parameters, including decreased compound muscle action potentials or delayed
      distal motor latency, were found in 34.2% (25/73) and 12.3% (9/73) of the
      patients, respectively. A total of 24.6% (18/73) of the patients showed decreased
      F-wave frequency. EMG demonstrated the presence of neurogenic lesions in all
      patients with spontaneous potentials, prolonged duration or augmentation of
      amplitude in motor unit potentials (MUPs), or a single pattern of MUP
      recruitment. About 17.8% (13/73) of the patients showed neurogenic lesions,
      mostly in the C7-8 level of the cervical cord, only in the upper extremity of
      affected side, whereas 35.6% (26/73) of the patients possessed lesions in the
      upper extremities bilaterally. A total of 46.6% (34/73) of patients exhibited
      abnormalities in the lower extremities, sterno- cleidomast or thoracic
      paravertebral muscle. Changes in motor NCS were significantly correlated with
      muscle strength. CONCLUSIONS: EMG detects diffused subclinical neurogenic lesion
      in a high proportion of patients with Hirayama disease. Results of our study
      challenge the hypothesis that Hirayama disease is a type of cervical myelopathy.

PMID- 22613539
TI  - Expression of the recepteur d'originenantais receptor tyrosine kinase in non
      small cell lung cancer and its clinical significance.
AB  - BACKGROUND: Recepteur d'originenantais (RON) is a receptor tyrosine kinase (RTK)
      that belongs to the MET proto-oncogene family. The aim of this study was to
      investigate the expression of RON receptor tyrosine kinase in human non-small
      cell lung cancer (NSCLC) and its relationship with clinical pathology of NSCLC
      and prognosis. METHODS: RON protein expression by immunohistochemistry (IHC) in
      96 NSCLC specimens was evaluated and compared with the clinical pathology and
      prognosis, and 20 para-neoplastic tissues were included as controls. RON mRNA and
      protein expression in 25 fresh tissue samples of lung cancer and 10 normal lung
      tissues were also analyzed by reverse transcription-polymerase chain reaction (RT
      PCR) and Western blotting. RESULTS: The rate of positive RON expression differed
      significantly between NSCLC tissues (55.2%, 53/96) and para-neoplastic tissues
      (5%, 1/20) (P < 0.001). RON protein expression was not found to be associated
      with gender or age. However, RON expression positively correlated with clinical
      TNM stage (P = 0.004), histological types (P = 0.001), lymph node metastasis (P =
      0.012) and differentiation (P = 0.035). RT-PCR and Western blotting analysis also
      confirmed that the expression of RON mRNA and protein was significantly increased
      in the NSCLC tissues versus normal tissues. In addition, RON expression was
      associated with a poor prognosis for patients with NSCLC (P = 0.045).
      CONCLUSIONS: The expression of RON protein and mRNA is significant in human NSCLC
      and low in para-neoplastic and normal tissues. Elevated RON expression may
      contribute to the occurrence, progression and metastasis of NSCLC, inferring that
      it could be useful as a new prognostic indicator for patients with NSCLC.

PMID- 22613541
TI  - Correlation between T lymphocyte subsets in peripheral blood lymphocytes and 2
      year all-cause mortality in an apparently healthy elderly Chinese cohort.
AB  - BACKGROUND: Few data have been acquired on the predictive value of age-related T
      lymphocyte subsets among older individuals. The present study has determined the
      distribution of T-cell phenotypes and their correlation to 2-year mortality in a
      cohort of Chinese male seniors. METHODS: A total of 101 asymptomatic elderly
      individuals with laboratory homeostasis were enrolled at baseline. Three age
      subgroups were categorized as young (65 - 74 years old), middle (75 - 84 years
      old), and old (>= 85 years) for age-related comparison. T-cell subsets in
      peripheral blood were measured by multi-colored flow cytometry. RESULTS: At
      baseline, there was a mild negative correlation by age for total lymphocytes and
      CD3(+) T-cells. The frequency of CD28 and CD95 demonstrated a "curved" rather
      than linear tendency by age. At 2-year follow-up, little change of T-cell
      distribution was found among those who remained alive (as survivors) comparing
      the data at baseline to the 2-year time point. Immune risk phenotypes were
      distinctly demonstrated between survivors and non-survivors. CONCLUSIONS: Since
      few studies have studied on the distribution of T-lymphocyte subsets in an
      elderly Chinese population, our results have not only provided reference values
      of T-subsets for aged Chinese men, but confirmed the immune risk phenotypes among
      elderly Chinese. The inappropriate age-dependent trajectory of CD28(-)/CD8(+) and
      CD95(-)/CD8(+) by age, which suggested 85 might be an inflexion point of age
      during T-cell ageing, warrants further exploration of the underlying mechanisms
      of T-cell ageing.

PMID- 22613543
TI  - A retrospective comparison of the efficacy and safety in kidney transplant
      recipients with basiliximab and anti-thymocyte globulin.
AB  - BACKGROUND: Induction therapy are utilized to achieve an adequate
      immunosuppression at the time of transplantation. The use of basiliximab or anti
      thymocyte globulin (ATG) for induction therapy has significantly reduced the
      incidence of acute rejection episodes post-transplantation. The purpose of this
      study was to compare the efficacy and safety of the basiliximab in patients with
      immuno-induction therapy after kidney transplantation with the ATG. METHODS: A
      retrospective analysis was carried out in kidney transplant recipients including
      146 patients with the basiliximab and 116 cases with the ATG and the acute
      rejection, graft function, infective complications and 1-year and 5-year
      actuarial patient and graft survival after renal transplantation were compared
      between the two treatment groups. RESULTS: There were no statistically
      significant difference between groups regarding age, sex, cold ischemic time,
      warm ischemic time, human leukocyte antigen (HLA) matching type between the donor
      and recipient, lymphotoxin test and the use of immunosuppressive agents. There
      was no statistical significance regarding the incidence of the acute rejection
      (9.59% vs. 8.62%, P = 0.481) and delayed graft function (10.27% vs. 9.48%, P =
      0.501) between groups. There were significantly lower lung infection incidence
      (5.48% vs. 12.93%, P = 0.029) in the basiliximab-treated group in comparison with
      the ATG-treated group. One-year patient and graft survival rates were 98%, 97%
      for the basiliximab-treated group, and 95%, 73% for the ATG-treated group,
      respectively. Five-year patient and graft survival rates were 92%, 86% for the
      basiliximab-treated group and 93%, 72% for the ATG-treated group, respectively.
      Log rank test showed statistically significant difference with P = 0.038 for
      patients and P = 0.033 for grafts, respectively. There were significantly lower
      the incidence of granulocytopenia (8.22% vs. 17.24%, P = 0.022) and
      thrombocytopenia (4.11% vs. 19.83%, P = 0.000) after transplantation in the
      basiliximab-treated group in comparison with the ATG-treated group. There was no
      statistical significance regarding the incidence of the heart dysfunction after
      transplantation between the two groups (6.16% vs. 6.90%, P = 0.502). CONCLUSION:
      The immuno-induction therapy with the basiliximab in kidney transplant recipients
      is efficient and safe with less complication compared with the ATG.

PMID- 22613542
TI  - ANKRD7 and CYTL1 are novel risk genes for alcohol drinking behavior.
AB  - BACKGROUND: Alcohol dependence (AD) is a complex disorder characterized by
      impaired control over drinking. It is determined by both genetic and
      environmental factors. The recent approach of genome-wide association study
      (GWAS) is a powerful tool for identifying complex disease-associated
      susceptibility alleles, however, a few GWASs have been conducted for AD, and
      their results are largely inconsistent. The present study aimed to screen the
      loci associated with alcohol-related phenotypes using GWAS technology. METHODS: A
      genome-wide association study with the behavior of regular alcohol drinking and
      alcohol consumption was performed to identify susceptibility genes associated
      with AD, using the Affymetrix 500K SNP array in an initial sample consisting of
      904 unrelated Caucasian subjects. Then, the initial results in GWAS were
      replicated in three independent samples: 1972 Caucasians in 593 nuclear families,
      761 unrelated Caucasian subjects, and 2955 unrelated Chinese Hans. RESULTS:
      Several genes were associated with the alcohol-related phenotypes at the genome
      wide significance level, with the ankyrin repeat domain 7 gene (ANKRD7) showing
      the strongest statistical evidence for regular alcohol drinking and suggestive
      statistical evidence for alcohol consumption. In addition, certain haplotypes
      within the ANKRD7 and cytokine-like1 (CYTL1) genes were significantly associated
      with regular drinking behavior, such as one ANKRD7 block composed of the SNPs
      rs6466686-rs4295599-rs12531086 (P = 6.51 * 10(-8)). The association of alcohol
      consumption was successfully replicated with rs4295599 in ANKRD7 gene in
      independent Caucasian nuclear families and independent unrelated Chinese Hans,
      and with rs16836497 in CYTL1 gene in independent unrelated Caucasians. Meta
      analyses based on both the GWAS and replication samples further supported the
      observed significant associations between the ANKRD7 or CYTL1 gene and alcohol
      consumption. CONCLUSION: The evidence suggests that ANKRD7 and CYTL1 genes may
      play an important role in the variance in AD risk.

PMID- 22613544
TI  - Preventive and therapeutic effects of penehyclidine hydrochloride on morphine
      induced increased bladder pressure, urinary bladder sphincter pressure and
      histological damage in rabbits.
AB  - BACKGROUND: Morphine has become the preferred drug for analgesia. However,
      analgesic doses of morphine can result in urinary retention, which is an
      intractable problem in clinical practice. Though bladder catheterization is one
      available therapeutic option, data supporting the technique's effectiveness are
      controversial. As a novel anti-cholinergic medicine developed in China,
      penehyclidine hydrochloride (PHC) exhibits greater selectivity for M(3)/M(1)
      receptors than M(2) receptors. Therefore, this study aimed to determine the
      efficacy of PHC in treating urinary retention. METHODS: Thirty-two healthy male
      New Zealand white rabbits were randomly divided in four groups (n = 8 each) as
      follows: control group (C group), PHC low-dose group (PL group, 0.01 mg/kg of PHC
      intramuscularly), PHC middle-dose group (PM group, 0.02 mg/kg of PHC
      intramuscularly), and PHC high-dose group (PH group, 0.05 mg/kg of PHC
      intramuscularly). All rabbits were injected intravenously with morphine (1 mg/kg)
      to induce urinary retention and different doses of PHC were injected
      intramuscularly in the PL, PM and PH groups. In the C group, 1 ml saline was
      administered instead of PHC. The bladder pressure and the bladder sphincter
      pressure were recorded at different time points. The plasma concentration of PHC
      was measured at different time points with high performance liquid
      chromatography. Arterial blood pressure and heart rate (HR) were recorded at
      different time points. RESULTS: Bladder pressure and urinary bladder sphincter
      pressure rose significantly from 30 minutes after morphine administration until
      the end of the experiment. PHC markedly attenuated the elevations in pressure
      induced by morphine. Morphometric analysis also revealed histological damage,
      erythrocytes and ruptures of the microcirculation in regions of the submucosa and
      smooth muscle. Morphometric damage was ameliorated with PHC but not with saline.
      Hemodynamic data (mean arterial pressure (MAP) and HR) did not differ between
      groups over the observation period. CONCLUSIONS: This study demonstrated that
      intravenous morphine significantly increased bladder pressure and urinary bladder
      sphincter pressure and induced histological damage in the bladder and urinary
      bladder sphincter. Importantly, preliminary data showed that PHC could decrease
      the extent of these changes.

PMID- 22613545
TI  - Influence of irbesartan on the urinary excretion of cytokines in patients with
      chronic kidney disease.
AB  - BACKGROUND: The non-hemodynamic effects of angiotensin receptor blocker (ARB) in
      the delay of progression of chronic kidney disease (CKD) remain unclear. In this
      study, we investigated the influence of irbesartan on the urinary excretion of
      cytokines in patients with CKD. METHODS: In this randomized perspective clinical
      trial, different doses of irbesartan (150 mg/d and 300 mg/d) were given to two
      groups of patients in a cross-over design. Blood pressure (BP), creatinine
      clearance (Ccr) and 24-hour proteinuria were examined. Urinary excretion of
      cytokines was determined by human inflammatory cytokine antibody array. A two
      fold change in spot intensity was considered significant. RESULTS: Urinary
      excretion of cytokines (granulocyte colony stimulating factor (GCSF),
      intercellular cell adhesion molecule-1 (ICAM-1), interferon gamma (IFN-gamma),
      interleukin 1beta (IL-1b), IL-2, IL-6, IL-8, IL-11, IL-15 and macrophage
      inflammatory protein 1d (MIP-1d)) in group B (irbesartan 300 mg/d) was
      significantly decreased in comparison to group A (irbesartan 150 mg/d) after 8
      week treatment. In group A, 8 weeks of treatment induced a two- to nine-fold
      reduction in urinary cytokine levels (GCSF, GM-CSF, IFN-gamma, IL-1a, IL-11, IL
      12p40, MCP-2, MIP-1a), while increasing the dosage to 300 mg/d further decreased
      the excretion of GCSF, GM-CSF, IL-12p40, MCP-2 and MIP-1a by week 18. There was
      no significant difference in BP or Ccr between the two groups. However, 24-hour
      proteinuria was significantly reduced in both groups, and in group A the
      reduction was dose dependent. CONCLUSION: Irbesartan offers additional
      renoprotection in a dose-dependent manner by reducing pro-inflammatory cytokines
      excretion in the urine of CKD patients.

PMID- 22613546
TI  - Contraceptive knowledge, attitudes and behavior about sexuality among college
      students in Beijing, China.
AB  - BACKGROUND: Sexual and reproductive health among adolescents have become
      increasingly important and aroused international concerns. In this study, we
      investigate sexual knowledge, attitudes, sexual behaviors, the unwanted pregnancy
      and the abortion rate and to explore related determinants among college students
      in Beijing. METHODS: This study is based on a cross-sectional survey of college
      students' knowledge, attitudes and behavior. Multistage cluster sampling was used
      to select subjects in Beijing. The self-questionnaire designed by our research
      group including general information, knowledge, attitude and behavior about
      sexuality was used to collect information. A total of 2003 questionnaires were
      collected from June to July 2010. RESULTS: The data showed that most of the
      college students lacked knowledge about reproductive health. Only 17.9% of the
      respondents knew the appropriate time of abortion. Data also showed that the
      respondents had high-risk attitude about sex, 58.7% could accept premarital sex,
      and 29.7% had negative attitude towards contraception. Moreover, sexual activity
      of the respondents was active. Data showed that 18.5% of the respondents had had
      sexual activities. Significantly more boys than girls had sex (chi(2) = 73.374, P
      < 0.001). Among the boys and girls who reported sexual history, 43.1% of the boys
      had impregnated girlfriend and 49.3% of the girls among those people who have sex
      had unwanted pregnancies. Logistic regression analysis showed that the variables
      the gender (OR = 3.12, 95%CI: 2.39 - 4.11), grade (OR = 1.78, 95%CI: 1.40 -
      2.26), specialty (OR = 1.35, 95%CI: 1.12 - 1.74), family situation (OR = 1.66,
      95%CI: 1.15 - 2.38), score of knowledge (OR = 0.74, 95%CI: 0.58 - 0.95) and
      attitude to sex activity (OR = 0.09, 95%CI: 0.04 - 0.22) had a significant effect
      on having sexual behavior. CONCLUSIONS: College students lack knowledge and
      methods to avoid risky sexual behaviors in Beijing. College students have high
      risk sexual attitude and behaviors. Therefore, suitable and effective sex health
      measures to protect college students would be strongly recommended.

PMID- 22613547
TI  - Serosa-penetration in human T4aN0M0 gastric carcinoma correlates with worse
      prognosis after D2 gastrectomy.
AB  - BACKGROUND: In both the seventh edition of the International Union Against Cancer
      (UICC) staging system for gastric cancer and the 14th edition of the Japanese
      Gastric Cancer Association (JGCA) system, T(4a) is defined as "Tumor perforates
      serosa (visceral peritoneum) without invasion of adjacent structures." The aim of
      this study was to investigate the differences in prognosis between patients with
      serosa-penetrating and serosa-invading T(4a)N(0)M(0) gastric carcinomas. METHODS:
      Data were collected from 221 patients with T(4a)N(0)M(0) gastric carcinoma who
      underwent D2 resection at our cancer center between January 1990 and December
      2008. The cohort included 42 patients with serosa-penetrating tumors and 179
      patients with serosa-invading tumors. The average follow-up time was 85.5 months.
      Spearman's rank correlation, Kaplan-Meier plots, and Cox proportional hazards
      regression models were used to analyze the data. RESULTS: The 5-year survival
      rate of patients with serosa-penetrating and serosa-invading gastric cancers were
      31% and 62% respectively (P < 0.05). The relapse rates after D2 radical surgery
      were 16.2% in patients with serosa-invading gastric cancer versus 59.5% in those
      with serosa-penetrating tumors (P < 0.05). Peritoneal dissemination and distant
      organ/lymph node metastatic rates were 76.0% and 24.0% respectively in patients
      with penetrating tumors, versus 44.8% and 55.2% respectively in patients with
      invading tumors (P < 0.05). Multivariate analysis showed that penetration of the
      serosa was an independent prognostic indicator of overall survival. CONCLUSIONS:
      Our findings provide a basis for the concept that serosa-penetrating
      T(4a)N(0)M(0) gastric carcinoma represents a more aggressive cancer than serosa
      invading T(4a)N(0)M(0) gastric carcinoma. Serosa penetration is an independent
      factor for poor prognosis of patients with gastric carcinoma.

PMID- 22613548
TI  - Microbial diversity in failed endodontic root-filled teeth.
AB  - BACKGROUND: Persistent/secondary infections of human root canals play an
      important role in the failure of endodontic treatment. This study used 16S rRNA
      sequencing to assess microbial diversity in root-filled teeth associated with
      failed endodontic treatment. METHODS: DNA was extracted from 15 teeth with
      persistent intraradicular infections, and the 16S rRNA of all present bacteria
      were amplified by PCR, followed by cloning and sequencing of the 16S rRNA
      amplicons. RESULTS: All sample extracts were positive for PCR amplification using
      the universal 16S rRNA gene primers. Negative control reactions yielded no
      amplicons. Sixty-five phylotypes belonging to seven phyla were identified from
      760 clones; a mean of 9.4 phylotypes were detected in each sample (range 3 - 15).
      Twenty-eight phylotypes were detected in more than one sample, revealing a high
      inter-sample variability. Parvimonas micra (60%, 9/15), Solobacterium moore (47%,
      7/15), Dialister invisus (33%, 5/15), Enterococcus faecalis (33%, 5/15),
      Filifactor alocis (27%, 4/15), and Fusobacterium nucleatum (27%, 4/15) were the
      prevalent species. Nineteen as-yet-uncultivated phylotypes were identified,
      comprising a substantial proportion of the bacteria in many cases. CONCLUSIONS:
      Persistent intraradicular infections were present in all root-filled teeth
      associated with failed endodontic treatment. The current observations reveal new
      candidate endodontic pathogens, including as-yet-uncultivated bacteria and
      phylotypes that may participate in the mixed infections associated with post
      treatment apical periodontitis.

PMID- 22613549
TI  - In vivo transplantation of bone marrow mesenchymal stem cells accelerates repair
      of injured gastric mucosa in rats.
AB  - BACKGROUND: Adult stem cells provide a promising alternative for the treatment of
      injured tissues. We aimed to investigate the effect of in vivo transplantation of
      bone marrow mesenchymal stem cells (BMMSCs) on injured gastric mucosa in rats.
      METHODS: The gastric ulcer in rats was induced by indomethacin. BMMSCs from male
      rats, labeled with the fluorescent cell linker 5,6-carboxyfluorescein diacetate
      succinimidyl ester (CFDA SE), were transplanted into the female rats via tail
      vein injection. The healing process of gastric ulcers was monitored by HE
      staining. The protein levels of vascular endothelial growth factor (VEGF) and the
      epidermal growth factor receptor (EGFR) in the injured gastric mucosa were
      determined by immunohistochemistry. RESULTS: At 48 and 72 hours after BMMSCs
      transplantation, the CFDA SE labeled cells were found scattered in the injured
      gastric mucosa, but not in the gastric mucosa of control rats. At 72 hours after
      BMMSCs transplantation, the mean ulcer index was 12.67 +/- 2.16 in the BMMSCs
      transplanted group and 17.33 +/- 1.97 in vehicle-treated controls (P < 0.01).
      Both VEGF and EGFR protein expression levels were significantly higher in the
      gastric section from the rats that received BMMSCs transplantation as compared to
      rats without BMMSCs transplantation. CONCLUSION: Autologous BMMSCs
      transplantation can accelerate gastric ulcer healing in injured gastric mucosa in
      a rodent model.

PMID- 22613550
TI  - Catheter ablation of persistent atrial fibrillation with and without a history of
      paroxysmal atrial fibrillation.
AB  - BACKGROUND: It is unclear whether a history of paroxysmal atrial fibrillation
      (PAF) would impact the effect of catheter ablation on persistent atrial
      fibrillation (AF). This study aimed to compare the effect of catheter ablation on
      persistent AF with and without a history of PAF. METHODS: One hundred and eighty
      three patients underwent catheter ablation of persistent AF lasting for > 1 month
      and were reviewed. Patients were divided into two groups according to whether
      they had a history of PAF or not. Group I consisted of persistent AF patients
      with a history of PAF, and group II consisted of persistent AF patients without
      such a history. All patients received catheter ablation focused on pulmonary vein
      isolation and were observed for arrhythmia recurrences, which were defined as
      documented episodes of AF or atrial tachycardia after a blanking period of 3
      months. RESULTS: One hundred and three patients (60.9%) in group I and sixty-six
      patients (39.1%) in group II were successfully followed and included in analysis.
      There were no significant differences in clinical and echocardiographic
      characteristics between both groups except for a younger age and more male
      patients in group II. After (15.5 +/- 10.7) months of follow-up, 59 (57.3%)
      patients in group I and 49 (74.2%) patients in group II maintained sinus rhythm
      free of anti-arrhythmia drugs (P = 0.025). Multivariate analyses found left
      atrial anteroposterior diameter (P = 0.006) and persistent AF with a history of
      PAF (OR 1.792, 95%CI 1.019 - 3.152; P = 0.043) as the only independent
      statistical predictors of arrhythmia recurrences. CONCLUSION: The arrhythmia
      recurrence rate of catheter ablation based on pulmonary vein isolation in
      persistent AF with a history of PAF was higher than those without a history of
      PAF.

PMID- 22613551
TI  - Improved approach to atrial septum puncture: experience in 539 cases.
AB  - BACKGROUND: The transseptal puncture technique has been widely used in
      therapeutic left atrium catheterization. But this technique may lead to some life
      threatening complications. It can not be used widely because it is restricted by
      economy and deferring the transseptal puncture procedure. The aim of this study
      was to introduce a simple and safe transseptal puncture procedure. METHODS: The
      distal of coronary sinus (CS) electrode was positioned close to the lateral
      margin of heart, which was about at 3 o'clock at left anterior oblique (LAO) 30
      degrees  referred to whole cardiac profile. It was then used as the marker for
      the level of fossa ovalis at posterior-anterior projection to guide the pull of
      transseptal needle. The midpoint between the distal CS and the posterior margin
      of heart at right anterior oblique (RAO) 45 degrees  view was considered as the
      location of fossa ovalis. Once the puncture was succeeded, the guidewire was
      introduced to the left superior pulmonary vein via puncture sheath after the
      needle was retrieved. The end of outer sheath was introduced into left atrium
      with the protection of guidewire. It was applied in 539 patients (316 male, 223
      female; (53 +/- 16) years old) who underwent catheter ablation of atrial
      fibrillation or left-sided atrioventricular accessory pathway. RESULTS: This
      transseptal approach reached 100.0% success and was succeeded in 98.9% with the
      first attempt. The first attempt puncture was aborted due to greater resistance
      to needle advancement or smaller needle curve in six patients. However, the
      second attempts were all succeeded after the needle curve was reshaped. There was
      no tamponade and embolism occurred. CONCLUSION: The atrial septum puncture
      approach using the location of distal CS electrode as important marker and the
      guidewire for protection when sending outer sheath into left atrium is reliable
      and safe.

PMID- 22613552
TI  - Childhood leukemia genetic bottleneck phenomenon related to TEL-AML1: the
      postulation by a mathematical model.
AB  - Childhood leukemia bottleneck phenomenon is the most mysterious corollary of the
      prenatal origin discovery of leukemogenic chromosome translocations. The
      bottleneck is evidence that leukemia initiation, by in utero acquired chromosome
      translocations that generate functional fusion genes, is far more common than the
      incidence rate of corresponding leukemia. For childhood TEL-AML1(+) acute
      lymphoblastic leukemia (ALL) this equates to approximately 100 times. Practically
      this means that among a hundred children born with TEL-AML1 fusion gene, only one
      child will later in its life develop ALL. The key data necessary for unraveling
      of this mystery were discovered in 2002. It was the level of TEL-AML1(+) cells'
      frequency. The bottleneck is caused by the very low body TEL-AML1(+) cell count.
      Only one out of a thousand B cells carries TEL-AML1 fusion gene. TEL-AML1(+) body
      cell count is low because TEL-AML1 fusion is generated at cell level of 10(-3) to
      10(-4) just during the late fetal lymphopoiesis i.e. after the 36th gestational
      week.

PMID- 22613553
TI  - Local aneurysmal dilatation mimicking stent malapposition and concurrent
      vulnerable plaque within neointima of normal lumen after drug-eluting stent
      implantation: primary new findings from optical coherence tomography.
AB  - Very late stent thrombosis is a life-threatening complication of implantation of
      drug-eluting stent (DES). The mechanisms are still unidentified. Stent
      malapposition is supposed to be one debated reason. Here we report a case of 33
      months after DES implanted. Observed by optical coherence tomography, we detected
      a lipid-rich plaque with defective fibrous cap within the neointima and many
      local aneurysmal dilatations between stent struts, which mimic "malapposition" on
      the angiogram. These indicated that vulnerable plaque hidden in the neointima at
      the stent segment might be a potential mechanism of very late stent thrombosis
      after DES implantation.

PMID- 22613554
TI  - A case of severe preeclampsia diagnosed as post-partum hemolytic uremic syndrome.
AB  - Post-partum hemolytic uremic syndrome (PHUS) is a severe thrombotic
      microangiopathy clinically characterized by hemolytic anemia, renal dysfunction,
      and low platelets after birth with rapid progression and poor prognosis. Here, we
      reported a rare case of severe preeclampsia diagnosed as hemolytic uremic
      syndrome after birth. The patient was diagnosed with PHUS and underwent
      intermittent plasma exchange with supportive treatment including glucocorticoid
      injections and transfusion of suspended red blood cells. After these treatments,
      the patient experienced no apparent remission and chronic renal dysfunction
      occurred on her. PHUS is a severe emergency with acute onset, rapid progress, and
      poor prognosis. Early detection, diagnosis, and treatment can significantly
      improve the prognosis.

PMID- 22613555
TI  - Adrenocorticotropic hormone-producing pheochromocytoma: a case report and review
      of the literature.
AB  - Ectopic Cushing's syndrome caused by pheochromocytoma is rare. We reported a 15
      year-old female patient who was admitted to hospital with typical Cushing's
      syndrome. She had not started menstruation. Her plasma adrenocorticotropic
      hormone (ACTH) and 24-hour urinary free cortisol levels were extremely high.
      Gonadal and progestational hormone levels were also abnormal. Abdominal computed
      tomography scans and enhanced scans revealed multiple irregular tumors in the
      right adrenal. Pelvic echogram showed an infantile uterus, while the ovaries were
      at an immature stage of development. Retroperitoneal laparoscopic right
      adrenalectomy was performed without intraoperative complications. Histology and
      immunohistochemistry of the tumor were consistent with pheochromocytoma.
      Retroperitoneal laparoscopic adrenalectomy is a safe procedure with satisfactory
      outcomes and allows for rapid recovery.

PMID- 22613556
TI  - Idiopathic pulmonary vein thrombosis extending to left atrium: a case report with
      a literature review .
AB  - Pulmonary vein thrombosis is a rare disease and is usually represented as a
      complication of atrial fibrillation, pulmonary tumors, and lobectomy. Although it
      is a potentially life threatening condition, the venous disease is easy to
      misdiagnose because of the non-specific symptoms. In this article, we present a
      30-year-old patient who suffered from pulmonary vein thrombosis without any
      causes. He was diagnosed with other pulmonary disorders till the thrombus within
      the pulmonary vein extended into the left atrium. Left atrium mass resection and
      a left lower lobectomy were undertaken with relative urgency. The postoperative
      course was uneventful. The patient received a long course of oral anticoagulant
      therapy.

PMID- 22613557
TI  - Identification of a potential tumor differentiation factor receptor candidate in
      prostate cancer cells.
AB  - Tumor differentiation factor (TDF) is a pituitary protein that is secreted into
      the bloodstream and has an endocrine function. TDF and TDF-P1, a 20-residue
      peptide selected from the ORF of TDF, induce differentiation in human breast and
      prostate cancer cells, but not in other cells. TDF has no known mechanism of
      action. In our recent study, we identified heat shock 70 kDa proteins (HSP70s) as
      TDF receptors (TDF-Rs) in breast cancer cells. Therefore, we sought to
      investigate whether TDF-R candidates from prostate cancer cells are the same as
      those identified in breast cancer cells. Here, we used TDF-P1 to purify the
      potential TDF-R candidates by affinity purification chromatography from DU145 and
      PC3 steroid-resistant prostate cancer cells, LNCaP steroid-responsive prostate
      cancer cells, and nonprostate NG108 neuroblastoma and BLK CL.4 fibroblast-like
      cells. We identified the purified proteins by MS, and validated them by western
      blotting, immunofluorescence microscopy, immunoaffinity purification
      chromatography, and structural biology. We identified seven candidate proteins,
      of which three were from the HSP70 family. These three proteins were validated as
      potential TDF-R candidates in LNCaP steroid-responsive and in DU145 and PC3
      steroid-resistant prostate cancer cells, but not in NG108 neuroblastoma and BLK
      CL.4 fibroblast-like cells. Our previous study and the current study suggest that
      GRP78, and perhaps HSP70s, are strong TDF-R candidates, and further suggest that
      TDF interacts with its receptors exclusively in breast and prostate cells,
      inducing cell differentiation through a novel, steroid-independent pathway.

PMID- 22613558
TI  - [Nursing in Spain: the current situation and possible strategies].

PMID- 22613559
TI  - [Attitude and behaviour of women to prevention of cardiovascular disease].

PMID- 22613560
TI  - [Reply to letter to the editor].

PMID- 22613561
TI  - The uncoupling protein 2 -866G > a polymorphism is associated with the risk of
      ischemic stroke in Chinese type 2 diabetic patients.
AB  - AIMS: To determine genetic predispsitions for diabetic cerebral ischemia, we
      investigated the relationship between the -866G>A polymorphism of uncoupling
      protein (UCP) 2 and the risk of ischemic stroke in two cohorts of type 2 diabetic
      patients. METHODS: A total of 844 type 2 diabetic patients with 4-year
      prospective study were examined using a case-control methodology. And 404 cases
      with ischemical stroke, 440 cases without ischemical stroke. The -866G>A
      polymorphism in UCP2 was genotyped by TaqMan MGB probe method. RESULTS: The 
      866G>A SNP in UCP2 was significantly associated with diabetic ischemical stroke
      (odds ratio [OR]= 1.94; 95% confidence interval [CI]= 0.68 to1.31; P < 0.037).
      Similar results were observed for baseline cases of IS. Stratification by sex
      confirmed an allelic association with IS in women, whereas no association was
      observed in men. CONCLUSIONS: The A allele of the -866G>A variant of UCP2 was
      associated with increased risk of IS in Chinese diabetic women with type 2
      diabetes in a 4-year prospective study. This association was independent of other
      common IS risk factors.

PMID- 22613562
TI  - Flexible-meccano: a tool for the generation of explicit ensemble descriptions of
      intrinsically disordered proteins and their associated experimental observables.
AB  - MOTIVATION: Intrinsically disordered proteins (IDPs) represent a significant
      fraction of the human proteome. The classical structure function paradigm that
      has successfully underpinned our understanding of molecular biology breaks down
      when considering proteins that have no stable tertiary structure in their
      functional form. One convenient approach is to describe the protein in terms of
      an equilibrium of rapidly inter-converting conformers. Currently, tools to
      generate such ensemble descriptions are extremely rare, and poorly adapted to the
      prediction of experimental data. RESULTS: We present flexible-meccano-a highly
      efficient algorithm that generates ensembles of molecules, on the basis of amino
      acid-specific conformational potentials and volume exclusion. Conformational
      sampling depends uniquely on the primary sequence, with the possibility of
      introducing additional local or long-range conformational propensities at an
      amino acid-specific resolution. The algorithm can also be used to calculate
      expected values of experimental parameters measured at atomic or molecular
      resolution, such as nuclear magnetic resonance (NMR) and small angle scattering,
      respectively. We envisage that flexible-meccano will be useful for researchers
      who wish to compare experimental data with those expected from a fully disordered
      protein, researchers who see experimental evidence of deviation from 'random
      coil' behaviour in their protein, or researchers who are interested in working
      with a broad ensemble of conformers representing the flexibility of the IDP of
      interest. AVAILABILITY: A fully documented multi-platform executable is provided,
      with examples, at http://www.ibs.fr/science-213/scientific
      output/software/flexible-meccano/ CONTACT: martin.blackledge@ibs.fr.

PMID- 22613563
TI  - Eukaryotic expression vectors bearing genes encoding cytotoxic proteins for
      cancer gene therapy.
AB  - Cancer gene therapy is a promising direction for the treatment of cancer
      patients. A primary goal of all cancer therapies is to selectively target and
      kill tumour cells. Such therapies are administered via different approaches,
      including both viral and non-viral delivery; however, both methods have
      advantages and disadvantages. Transcriptional targeting enables genes encoding
      toxic proteins to be expressed directly in cancer cells. Numerous vectors have
      been created with the purpose of killing cancer cells, and some have successfully
      suppressed malignant tumours. Data concerning the function of vectors bearing
      genes that encode cytotoxic proteins under the control of different promoters,
      including tissue/tumour specific and constitutive promoters, is summarised here.
      This review focuses on vectors that bear genes encoding diphtheria toxin,
      Pseudomonas exotoxin A, caspases, gef, streptolysin, and melittin. Data
      describing the efficacy of such vectors have been summarised. Notably, there are
      vectors that killed cancer cell lines originating from the same type of cancer
      with differential efficiency. Thus, there is differential inhibition of cancer
      cell growth dependent on the cell line. In this review, the constructs employing
      genes whose expression induces cell death and the efficiency with which they
      suppress cancer cell growth will be summarised.

PMID- 22613568
TI  - Optimal noise reduction in 3D reconstructions of single particles using a volume
      normalized filter.
AB  - The high noise level found in single-particle electron cryo-microscopy (cryo-EM)
      image data presents a special challenge for three-dimensional (3D) reconstruction
      of the imaged molecules. The spectral signal-to-noise ratio (SSNR) and related
      Fourier shell correlation (FSC) functions are commonly used to assess and
      mitigate the noise-generated error in the reconstruction. Calculation of the SSNR
      and FSC usually includes the noise in the solvent region surrounding the particle
      and therefore does not accurately reflect the signal in the particle density
      itself. Here we show that the SSNR in a reconstructed 3D particle map is linearly
      proportional to the fractional volume occupied by the particle. Using this
      relationship, we devise a novel filter (the "single-particle Wiener filter") to
      minimize the error in a reconstructed particle map, if the particle volume is
      known. Moreover, we show how to approximate this filter even when the volume of
      the particle is not known, by optimizing the signal within a representative
      interior region of the particle. We show that the new filter improves on
      previously proposed error-reduction schemes, including the conventional Wiener
      filter as well as figure-of-merit weighting, and quantify the relationship
      between all of these methods by theoretical analysis as well as numeric
      evaluation of both simulated and experimentally collected data. The single
      particle Wiener filter is applicable across a broad range of existing 3D
      reconstruction techniques, but is particularly well suited to the Fourier
      inversion method, leading to an efficient and accurate implementation.

PMID- 22613569
TI  - Redesigning the single-chain variant of the restriction endonuclease PvuII by
      circular permutation.
AB  - The restriction endonuclease PvuII has been introduced as a sequence-specific
      cleavage module in highly-specific nucleases for gene targeting. Here, a
      structural reorganization of the single-chain variant of PvuII (scPvuII) was
      performed by circular permutation as a proof-of-concept in order to find out
      whether the relocated, new termini next to structural elements important for DNA
      recognition and catalysis could be used for the fusion with other regulatory
      protein domains. Three circularly permuted variants of scPvuII were obtained that
      all maintain the specific endonucleolytic activity of scPvuII.

PMID- 22613570
TI  - Origin of non-cardiac endothelial cells from an Isl1+ lineage.
AB  - The cardiovascular system consists of many cell types with distinct embryonic
      origins. Cells from an Islet1 (Isl1)-expressing progenitor population make a
      substantial contribution to the developing heart. We reasoned that cells derived
      from Isl1-expressing progenitors might contribute more widely to the
      cardiovascular system. We show that cells derived from an Isl1-expressing
      progenitor lineage make a wide contribution to the systemic vasculature and that
      embryos conditionally deficient for Rac1 within this cell population develop
      defects in the non-cardiac vasculature. These data define new roles for Isl1 in
      the developing embryo and demonstrate a contribution of Isl1-expressing
      progenitors to vascular endothelium in vivo.

PMID- 22613571
TI  - A plant microRNA regulates the adaptation of roots to drought stress.
AB  - Plants tend to restrict their horizontal root proliferation in response to
      drought stress, an adaptive response mediated by the phytohormone abscisic acid
      (ABA) in antagonism with auxin through unknown mechanisms. Here, we found that
      stress-regulated miR393-guided cleavage of the transcripts encoding two auxin
      receptors, TIR1 and AFB2, was required for inhibition of lateral root growth by
      ABA or osmotic stress. Unlike in the control plants, the lateral root growth of
      seedlings expressing miR393-resistant TIR1 or AFB2 was no longer inhibited by ABA
      or osmotic stress. Our results indicate that miR393-mediated attenuation of auxin
      signaling modulates root adaptation to drought stress.

PMID- 22613572
TI  - Thermo-mechanical properties of the cell surface assessed by atomic force
      microscopy.
AB  - Atomic force microscopy (AFM) in lateral force mode was applied to assess the
      microscale thermo-mechanical (frictional) properties of the air-dried cell
      surface in the wide temperature range (288-363K/15-90 degrees C). AFM
      investigated cell surface layer can be represented as a biocomposite composed of
      several layers including the glycocalyx, the membrane and the intercellular layer
      containing membrane (cortical) cytoskeleton. The cells with two different
      cytoskeleton structures, erythrocytes and thymocytes, were studied. Above a
      certain temperature (T(g)), the significant change in friction force with
      temperature was revealed for the both cell types whereas there was no similar
      change in their topography parameters. The experimentally determined value T(g)
      for erythrocyte samples was lower than that for thymocyte ones. Treating living
      cells with the cross-linking agent, glutaraldehyde, led to the weakening of the
      temperature dependence of air-dried cell surface frictional properties in the
      studied temperature range. Addition of oxidizing agent, peroxynitrite, to living
      cell suspensions changed the temperature dependence of air-dried cell surface
      frictional properties depending on cell type and peroxynitrite concentration. The
      obtained data indicate that the study of thermo-mechanical properties of air
      dried cells with AFM in lateral force mode provides expanded information on the
      structural characteristics of the living cell surface layer, and sets the stage
      for the development of AFM-based method (with using a lateral force mode) for the
      cell pathology diagnostics.

PMID- 22613573
TI  - Struma ovarii with follicular thyroid-type carcinoma and neuroendocrine
      component: case report.
AB  - Struma ovarii (SO) is a slow-growing ovarian neoplasm with thyroid tissue as its
      predominant component. It is an uncommon neoplasm, usually asymptomatic with an
      unknown risk of malignant transformation. Due to difficulties in assessing the
      rare biological nature and the discrepancies in the reported cases, a consensus
      on the appropriate treatment has not been definitively reached. A 50-year-old
      female was subjected to upper gut endoscopy which showed a 30-mm mass located in
      the gastric antrum, suggestive of mesenchimal tumor. Incidentally, a pelvic CT
      scan also documented a solid mass in the right adnexa, with morphological
      characteristics of ovarian neoplasm. The patient underwent gastrectomy, total
      hysterectomy, bilateral salpingo-oophorectomy with lymph node dissection, and
      omentectomy. Histology documented the presence of gastric cavernous angioma, and,
      in the right adnexa, foci of follicular thyroid-type carcinoma arising in SO with
      a well-differentiated neuroendocrine component.Here we report and discuss the
      clinical and morphological presentation of follicular thyroid-type carcinoma
      arising in SO. The neoplasm was discovered incidentally and had a favorable
      clinical outcome at 1-year follow-up.

PMID- 22613574
TI  - Determination of bovine lactoferrin in infant formula by capillary
      electrophoresis with ultraviolet detection.
AB  - A new and simple method for the quantitative determination of bovine lactoferrin
      (Lf) in infant formula by capillary electrophoresis with ultraviolet (CE-UV)
      detection was established. Effective sample pre-treatment and the addition of
      buffer additive to the running buffer played key roles in the accurate assay of
      the Lf in infant formula. In the method, the infant formula samples were
      pretreated with 50 mmol/L acetic acid without pH adjustment, which is beneficial
      for high sample throughput. The separation was carried out in an uncoated
      capillary with 50 MUm i.d. and total length of 27 cm (20 cm to the detector). The
      running buffer consisted of 40 mmol/L NaH2PO4, 40 mmol/L H3PO4 and 5 mmol/L
      polyethylene glycol dodecylether (Brij 35). The addition of the non-ionic
      surfactant Brij 35 to the running buffer served to suppress the Lf adsorption to
      the capillary wall, and also allowed for high-efficiency separation of Lf from
      adjacent unknown proteins. The intra- and inter-day precision of the method were
      2.4% and 4.6% (n=7), respectively. The corrected peak area (A(c)) and the
      concentration of Lf showed a strong linear relationship within the range of 10
      400 mg/L with a linear correlation coefficient (r) of 0.9999. The limit of
      detection (LOD) and limit of quantitation (LOQ) were 3mg/L (S/N=3) and 10mg/L
      (S/N=10), respectively. The method was successfully used to quantitate the Lf in
      infant formula with satisfactory results.

PMID- 22613579
TI  - Accidental decannulation following placement of a tracheostomy tube.
AB  - BACKGROUND: Accidental decannulation is a cause of substantial morbidity and
      mortality in patients in long-term acute care hospitals who require a
      tracheostomy tube. OBJECTIVE: To analyze features of accidental decannulation
      (AD) following placement of a tracheostomy tube, and to implement strategies to
      reduce the problem. METHODS: An analysis of data collected prospectively for
      quality management in a long-term acute care hospital was performed. RESULTS: AD
      occurred at a rate of 4.2 +/- 0.9/1,000 tracheostomy days over a 7 month period.
      Factors associated with AD included mental status changes, increased secretions,
      and change of shift. Following the implementation of a series of interventions
      (staff education on risk factors for AD and best tracheostomy care practice;
      increased availability of telemetry and oximetry; and signage to identify
      patients at high risk of AD), the incidence of AD over a subsequent 7 month
      period was significantly reduced, to 2.7 +/- 1.9/1,000 tracheostomy days. In
      addition the numbers of multiple, unmonitored, unreported, and night shift ADs
      were all significantly reduced. CONCLUSIONS: Targeted interventions can
      significantly reduce both the incidence of AD following tracheostomy and
      associated morbidity. Best practice guidelines to help minimize AD in patients
      with tracheostomy tubes are proposed.

PMID- 22613578
TI  - Astrocytes generated from patient induced pluripotent stem cells recapitulate
      features of Huntington's disease patient cells.
AB  - BACKGROUND: Huntington's Disease (HD) is a devastating neurodegenerative disorder
      that clinically manifests as motor dysfunction, cognitive impairment and
      psychiatric symptoms. There is currently no cure for this progressive and fatal
      disorder. The causative mutation of this hereditary disease is a trinucleotide
      repeat expansion (CAG) in the Huntingtin gene that results in an expanded
      polyglutamine tract. Multiple mechanisms have been proposed to explain the
      preferential striatal and cortical degeneration that occurs with HD, including
      non-cell-autonomous contribution from astrocytes. Although numerous cell culture
      and animal models exist, there is a great need for experimental systems that can
      more accurately replicate the human disease. Human induced pluripotent stem cells
      (iPSCs) are a remarkable new tool to study neurological disorders because this
      cell type can be derived from patients as a renewable, genetically tractable
      source for unlimited cells that are difficult to acquire, such as neurons and
      astrocytes. The development of experimental systems based on iPSC technology
      could aid in the identification of molecular lesions and therapeutic treatments.
      RESULTS: We derived iPSCs from a father with adult onset HD and 50 CAG repeats (F
      HD-iPSC) and his daughter with juvenile HD and 109 CAG repeats (D-HD-iPSC). These
      disease-specific iPSC lines were characterized by standard assays to assess the
      quality of iPSC lines and to demonstrate their pluripotency. HD-iPSCs were
      capable of producing phenotypically normal, functional neurons in vitro and were
      able to survive and differentiate into neurons in the adult mouse brain in vivo
      after transplantation. Surprisingly, when HD-iPSCs were directed to differentiate
      into an astrocytic lineage, we observed the presence of cytoplasmic, electron
      clear vacuoles in astrocytes from both F-HD-iPSCs and D-HD-iPSCs, which were
      significantly more pronounced in D-HD-astrocytes. Remarkably, the vacuolation in
      diseased astrocytes was observed under basal culture conditions without
      additional stressors and increased over time. Importantly, similar vacuolation
      phenotype has also been observed in peripheral blood lymphocytes from individuals
      with HD. Together, these data suggest that vacuolation may be a phenotype
      associated with HD. CONCLUSIONS: We have generated a unique in vitro system to
      study HD pathogenesis using patient-specific iPSCs. The astrocytes derived from
      patient-specific iPSCs exhibit a vacuolation phenotype, a phenomenon previously
      documented in primary lymphocytes from HD patients. Our studies pave the way for
      future mechanistic investigations using human iPSCs to model HD and for high
      throughput therapeutic screens.

PMID- 22613580
TI  - Deep sequencing-based transcriptome profiling analysis of Oryzias melastigma
      exposed to PFOS.
AB  - Oryzias melastigma is a newly emerging marine fish model. However, the
      application of this model has been restricted because of the lack of genomic
      information. Perfluorooctane sulfonate (PFOS), a persistent organic pollutant, is
      widely distributed in the estuarine/marine environment. The toxicological effects
      of PFOS on organisms, especially on marine fish species, remain largely unknown.
      In this study, the transcriptome of O. melastigma was sequenced using newly
      developed sequencing technology (Illumina RNA-seq). A total of 145,394 unigenes
      were obtained with 565 bp of unigene N50. These genes were further enriched in
      various molecular pathways involved in the toxicological response. We also
      investigated the transcriptional response of O. melastigma embryos after PFOS
      exposure from 2 days post fertilization (dpf) to 6 dpf by digital gene expression
      (DGE) technology. The differentially expressed genes were related to
      neurobehavioral defects, mitochondrial dysfunction and the metabolism of proteins
      and fats. A further quantitative RT-PCR study showed the down-regulation of ATP
      synthase and the up-regulation of uncoupling protein 2 (UCP2), which indicated
      mitochondrial dysfunction. In all, the transcriptome data represent the most
      comprehensive expressed gene catalog for O. melastigma and will serve as an
      important reference for various marine fish that are yet to be sequenced. The
      transcriptome profiling of O. melastigma embryos after exposure to PFOS are also
      expected to improve our current understanding of the molecular toxicology of
      PFOS.

PMID- 22613581
TI  - Comparative analysis of quinolizidine alkaloids from different parts of Sophora
      alopecuroides seeds by UPLC-MS/MS.
AB  - The seeds of Sophora alopecuroides L. have been utilized as a crude drug in China
      for thousands of years. Quinolizidine alkaloids are the main bioactive components
      of this plant. To determine the distribution and content of quinolizidine
      alkaloids in different seed organs (seed coat and cotyledon), a reliable method
      has been established using ultra-high-performance liquid chromatography coupled
      with a triple quadrupole electrospray tandem mass spectrometry (UPLC-MS/MS).
      Seven constituents, namely cytisine, oxymatrine, oxysophocarpine, sophoridine,
      sophoramine, matrine, and sophocarpine, were simultaneously determined in 10 min.
      The proposed method was fully validated in terms of linearity, sensitivity,
      precision, repeatability as well as recovery. The analysis results showed there
      were remarkable differences in the distribution and contents of the chemical
      markers between seed coat and cotyledon. The established approach could be
      helpful for the quality control of S. alopecuroides seeds, and also for the
      determination of this type class of alkaloids in other medicinal herbs. The
      present study can provide necessary information for the rational utilization of
      S. alopecuroides resources.

PMID- 22613582
TI  - Simultaneous determination of nine model compounds in permeability samples using
      RP-HPLC: application to prove the cassette administration principle in single
      pass intestinal perfusion study in rats.
AB  - A simple, sensitive and specific reversed phase high performance liquid
      chromatographic (RP-HPLC) method for simultaneous determination of atenolol,
      paracetamol, hydrochlorothiazide, caffeine, cephalexin, metoprolol, propranolol,
      ketoprofen along with phenol red (a non-absorbable compound) in samples obtained
      from intestinal in situ single-pass perfusion studies, was developed and
      validated. Chromatography was carried out on RP18 column with mobile phase
      comprising of 10 mM phosphate buffer (pH 2.5) and methanol in gradient mode. The
      calibration curves were linear for all nine permeability model compounds (r2 >
      0.999) across the concentration range of 1.25-40 MUg/ml. The coefficient of
      variation for intra and inter-day assay precision was between 0.04 and 3.08% and
      the accuracy was between 98.39 and 109.45%. Stability studies were carried out at
      different storage conditions and all the analytes were found to be stable. The
      method was successfully applied for analysing the permeability samples obtained
      from in situ single pass perfusion studies. The effective permeability (P(eff))
      values obtained upon cassette administration were in close proximity to the
      permeability values obtained upon single administration of model compounds. In
      conclusion, the developed RP-HPLC method can be used for high throughput cassette
      validation of rat in situ perfusion model for intestinal permeability assessment.

PMID- 22613583
TI  - Cisplatin resistance induced in germ cell tumour cells is due to reduced
      susceptibility towards cell death but not to altered DNA damage induction or
      repair.
AB  - To identify factors involved in cisplatin (CDDP) resistance of germ cell tumours
      (GCTs), we exposed NTERA-2 cells, and the platinum-adapted subline NTERA-2R to
      CDDP and compared their response. While both cell lines showed comparable
      proliferation, NTERA-2R cells were clearly more resistant to the drug than the
      parental NTERA-2 cell line. Interestingly, the two lines showed identical extent
      of DNA adduct formation and elimination, indicating that neither changes in CDDP
      uptake, nor altered drug efflux, DNA binding, or repair caused the difference in
      resistance. Similarly, no difference occurred in the time-course of gammaH2AX
      formation, which was not linked to 53BP1 accumulation. In contrast, NTERA-2R
      cells showed a more pronounced dose-dependent S phase delay, a transient G(2)/M
      block, and subsequent release into immediate cell death. We thus conclude that
      the enhanced resistance against CDDP is linked to reduced susceptibility to cell
      death rather than to an altered DNA adduct formation or adduct removal.

PMID- 22613584
TI  - Treatment of functional mitral regurgitation by percutaneous annuloplasty:
      results of the TITAN Trial.
AB  - AIMS: Functional mitral regurgitation (FMR) contributes to morbidity and
      mortality in heart failure (HF) patients. The aim of this study was to determine
      whether percutaneous mitral annuloplasty could safely and effectively reduce FMR
      and yield durable long-term clinical benefit. METHODS AND RESULTS: The impact of
      mitral annuloplasty (Carillon Mitral Contour System) was evaluated in HF patients
      with at least moderate FMR. Patients in whom the device was placed then acutely
      recaptured for clinical reasons served as a comparator group. Quantitative
      measures of FMR, left ventricular (LV) dimensions, New York Heart Association
      (NYHA) class, 6 min walk distance (6MWD), and quality of life were assessed in
      both groups up to 12 months. Safety and key functional data were assessed in the
      implanted cohort up to 24 months. Thirty-six patients received a permanent
      implant; 17 had the device recaptured. The 30-day major adverse event rate was
      1.9%. In contrast to the comparison group, the implanted cohort demonstrated
      significant reductions in FMR as represented by regurgitant volume [baseline 34.5
      +/-11.5 mL to 17.4 +/-12.4 mL at 12 months (P < 0.001)]. There was a
      corresponding reduction in LV diastolic volume [baseline 208.5 +/-62.0 mL to
      178.9 +/-48.0 mL at 12 months (P =0.015)] and systolic volume [baseline 151.8 +/
      57.1 mL to 120.7 +/-43.2 mL at 12 months (P =0.015)], compared with progressive
      LV dilation in the comparator. The 6MWD markedly improved for the implanted
      patients by 102.5 +/-164 m at 12 months (P =0.014) and 131.9 +/-80 m at 24 months
      (P < 0.001). CONCLUSION: Percutaneous reduction of FMR using a coronary sinus
      approach is associated with reverse LV remodelling. Significant clinical
      improvements persisted up to 24 months.

PMID- 22613585
TI  - A double-blind, randomized, parallel, placebo-controlled study examining the
      effect of cross-linked polyelectrolyte in heart failure patients with chronic
      kidney disease.
AB  - AIMS: This double-blind, randomized, parallel, placebo-controlled investigation
      evaluated the effects of cross-linked polyelectrolyte (CLP) on serum potassium
      and measures of congestion in patients with heart failure (HF) and chronic kidney
      disease (CKD). METHODS AND RESULTS: The primary endpoint was change in serum
      potassium over time. Exploratory endpoints included: weight, physician and
      patient assessment of exertional dyspnoea, effect on N-terminal pro brain
      natriuretic peptide (NT-proBNP) levels, New York Heart Association (NYHA)
      classification, 6 min walk test (6MWT), and quality of life by Kansas City
      Cardiomyopathy Questionnaire (KCCQ). Serum potassium was similar in CLP (n =59)
      and placebo (n =52) groups throughout the 8-week study. Weight loss was greater
      in the CLP than in the placebo group at Weeks 1 (P =0.014) and 2 (P =0.004), and
      this trend continued until the end of the study. After 8 weeks, by physician
      assessment, the percentage of patients experiencing marked or disabling dyspnoea
      tended to be lower in the CLP than in the placebo group (7.3% vs. 23.9%, P
      =0.128). Fewer patients in the CLP than in the placebo group had NT-proBNP levels
      >1000 pg/mL at Week 4 (P =0.039) and Week 8 (P =0.065). The proportion of
      patients improving by at least one NYHA functional class over the study was
      higher in the CLP than in the placebo group (48.8% vs. 17.4%; P =0.002). Effects
      on 6MWT at Week 8 (p =0.072) and quality of life (overall KCCQ score) at Week 4
      (p =0.005) and 8 (P =0.062) all favoured the CLP cohort. Four treatment-unrelated
      deaths occurred in the CLP group and none in the placebo group (P =0.056).
      CONCLUSION: In advanced, symptomatic HF with CKD, CLP is associated with
      beneficial clinical effects without significant serum potassium changes. TRIAL
      REGISTRATION: NCT01265524.

PMID- 22613586
TI  - Medicine is more than just knowledge or skill.

PMID- 22613587
TI  - Diagnosis and management of gestational diabetes mellitus in China.

PMID- 22613588
TI  - New considerations regarding pelvic organ prolapse treatment in China.
AB  - Pelvic organ prolapse (POP) is non-fatal conditions which can markedly affect a
      patient's quality of life. Multiple recently developed pelvic reconstructive
      surgeries have led to a recent expansion in China. In this study, we would like
      to discuss various aspects of the evaluation and management of POP and raise the
      question of what is sufficient evidence for the adoption of innovative treatments
      for POP.

PMID- 22613589
TI  - Diagnostic criteria for gestational diabetes mellitus (WS 331-2011).

PMID- 22613590
TI  - Treatment of respiratory failure in metastatic pulmonary choriocarcinoma: an
      experience at Peking Union Medical College Hospital, China.
AB  - BACKGROUND: Respiratory failure caused by metastatic pulmonary choriocarcinoma
      usually develops rapidly and is associated with a high mortality. The clinical
      management strategy is important in choriocarcinoma patients with acute
      respiratory failure. The objective of this study was to evaluate the clinical
      characteristics, treatment outcome and potential risk factors in patients with
      acute respiratory failure from metastatic pulmonary choriocarcinoma. METHODS:
      Sixteen patients with acute respiratory failure from pulmonary metastases
      choriocarcinoma were enrolled and treated at Peking Union Medical College
      Hospital from 1995 to 2010. Clinical characteristics, causes of pulmonary
      failure, treatment profiles and outcomes were analyzed retrospectively. RESULTS:
      The presence of respiratory infection or hemorrhage was associated with acute
      respiratory failure in patients with metastatic choriocarcinoma. Fifteen (93.8%)
      patients presented with pulmonary infection, 8 (50.0%) patients with pulmonary
      hemorrhage. All patients were treated with face mask or mechanical ventilation.
      Fourteen (87.5%) patients received initial chemotherapy at a low dosage or with
      modified regimens, with a median of 2 cycles (range 1 to 4). Seven patients
      achieved a complete remission (CR), two had a partial remission. Six CR patients
      remained alive with a median follow-up of 59 months (range 16 to 120). Seven
      patients developed progressive diseases and subsequently died. CONCLUSIONS:
      Respiratory infection and hemorrhage were associated with acute respiratory
      failure in metastatic pulmonary choriocarcinoma. The initial administration of
      gentle chemotherapy regimens, accompanied with mechanical ventilation, is
      feasible and effective in attenuating respiratory failure in patients with
      metastatic pulmonary choriocarcinoma.

PMID- 22613591
TI  - Risk factors for the development of vaginal intraepithelial neoplasia.
AB  - BACKGROUND: Vaginal intraepithelial neoplasia (VAIN), as a precursor of vaginal
      cancer, is a rare disease. Its prevalence has not been well analyzed. This
      research is to ascertain the risk factors for VAIN in a Chinese population.
      METHODS: A case-control study was conducted, including 63 VAIN cases and 64
      healthy controls. In all subjects Pap smear and HPV tests were performed. A
      questionnaire survey was distributed, covering information on socio-demographic
      characteristics, smoking, past history, reproductive and sexual histories. The
      clinical pathological data were collected from medical records including
      symptoms, Pap smear results, grade of lesions, and human papillomavirus (HPV)
      status. RESULTS: Postmenopausal women had a 2.09 times higher risk for VAIN than
      pre-menopausal women (95%CI: 1.10 - 3.85; P = 0.024). The patients with previous
      hysterectomy had an increased risk of VAIN (OR = 4.69; P = 0.003). Patients with
      a history of cervical cancer or CIN were predisposed to VAIN (OR = 78.75; P <
      0.0001). The rate of HPV infection in VAIN was significantly higher than in
      controls, and an increased risk of VAIN was observed in patients with higher
      viral load (OR = 126.00; P = 0.000). Multivariate analysis showed that HPV
      infection and a history of CIN or cervical cancer were still found to be
      significant in patients. CONCLUSION: HPV infection and a history of CIN or
      cervical cancer are the main risk factors for the development of VAIN.

PMID- 22613592
TI  - Increased hepatic peroxisome proliferator-activated receptor coactivator-1alpha
      expression precedes the development of insulin resistance in offspring of rats
      from severe hyperglycemic mothers.
AB  - BACKGROUND: Prenatal hyperglycaemia may increase metabolic syndrome
      susceptibility of the offspring. An underlying component of the development of
      these morbidities is hepatic gluconeogenic molecular dysfunction. We hypothesized
      that maternal hyperglycaemia will influence her offsprings hepatic peroxisome
      proliferator-activated receptor coactivator-1alpha (PGC-1alpha) expression, a key
      regulator of glucose production in hepatocytes. METHOD: We established maternal
      hyperglycaemia by streptozotocin injection to induce the maternal hyperglycaemic
      Wistar rat model. Offspring from the severe hyperglycemia group (SDO) and control
      group (CO) were monitored until 180 days after birth. Blood pressure, lipid
      metabolism indicators and insulin resistance (IR) were measured. Hepatic PGC
      1alpha expression was analyzed by reverse transcription polymerase chain reaction
      and Western blotting. mRNA expression of two key enzymes in gluconeogenesis,
      glucose-6-phosphatase (G-6-Pase) and phosphoenolpyruvate carboxykinase (PEPCK),
      were analyzed and compared. RESULTS: In the SDO group, PGC-1alpha expression at
      protein and mRNA levels were increased, so were expression of G-6-Pase and PEPCK
      (P < 0.05). The above effects were seen prior to the onset of IR. CONCLUSION: The
      hepatic gluconeogenic molecular dysfunction may contribute to the metabolic
      morbidities experienced by this population.

PMID- 22613593
TI  - Dehydroepiandrosterone indirectly inhibits human osteoclastic resorption via
      activating osteoblastic viability by the MAPK pathway.
AB  - BACKGROUND: Dehydroepiandrosterone (DHEA) is widely known for its beneficial
      effect on postmenopausal osteoporosis, although the underlying mechanisms remain
      mainly unclear. In this study, we tried to determine the activation of mitogen
      activated protein kinase signal pathways during DHEA treatment and the indirect
      role of osteoblasts (OBs) on osteoclasts under the DHEA treatment of
      postmenopausal osteoporosis. METHODS: Primary human OBs and osteoclast-like cells
      were cultured and, we pretreated OBs with or without U0126 (a highly selective
      inhibitor of both MEK1 and MEK2). The OBs were treated with DHEA. We then tested
      the effects of DHEA on human osteoblastic viability, osteoprotegerin production
      and the expression of phosphor-ERK1/2 (extracellular signal-regulated kinase). In
      the presence or absence of OBs, the function of osteoclastic resorption upon DHEA
      treatment was calculated. RESULTS: DHEA promoted the human osteoblastic
      proliferation and inhibited the osteoblastic apoptosis within the concentration
      range of 10(-8) - 10(-6) mol/L (P < 0.05, P < 0.01, respectively). Within the
      effective concentration range, the expression of phosphor-ERK1/2 and
      osteoprotegerin was increased by DHEA and blocked by U0126. In the presence of
      OBs, DHEA could significantly decrease the number and the area of bone resorption
      lacuna (P < 0.05 and P < 0.01, respectively). Without OBs, however, the effects
      of DHEA on the bone resorption lacuna were almost completely abolished.
      CONCLUSIONS: DHEA could indirectly inhibit the human osteoclastic resorption
      through promoting the osteoblastic viability and osteoprotegerin production,
      which is mediated by mitogen-activated protein kinases signal pathway involving
      the phosphor-ERK1/2.

PMID- 22613595
TI  - Anteroapical aneurysm plication improves mechanical intraventricular dyssynchrony
      in patients with anterior myocardial infarction.
AB  - BACKGROUND: Left ventricular (LV) dyssynchrony has been described to occur in
      patients with myocardial infarction. Dyssynchrony of left ventricular mechanical
      contraction produces adverse hemodynamic consequences. This study aimed to test
      the capacity of geometric rebuilding by aneurysm plication to restore a more
      synchronous contractile pattern after a mechanical, rather than electrical,
      intervention. METHODS: A total of sixty patients with anterior myocardial
      infarction, QRS duration < 120 ms, electively undergoing operation between
      January 2008 and January 2010 were included for analysis. Real-time 3-dimensional
      echocardiography was performed to assess LV function, LV systolic and diastolic
      dyssynchrony by measuring ejection fraction (EF), peak ejection rate (PER), peak
      filling rate (PFR) and LV dyssynchrony. LV dyssynchrony was defined as the
      systolic dyssynchrony of the time to reach the minimum systolic volume for 16 LV
      segments, expressed in percent cardiac cycle, systolic dyssynchrony index (SDI).
      We compared changes of LV dyssynchrony at different interval times. RESULTS: LV
      contraction was significantly asynchronous because preoperative SDI was higher,
      EF, PER and PFR were lowered. Compared with function after operation, LV
      mechanical intraventricular resynchronization was improved with decreased SDI
      ((8.7 +/- 0.5)% vs. (14.3 +/- 1.6)%, P = 0.01); LV function was improved with EF
      increasing ((43 +/- 9)% vs. (37 +/- 7)%, P = 0.001), and LV systolic and
      diastolic dyssynchrony was improved with more rapid PFR (199.4 +/- 15.6 vs. 148.4
      +/- 21.2, P = 0.002) and PER (212.4 +/- 14.5 vs. 156.3 +/- 26.2, P = 0.001).
      CONCLUSIONS: Systolic and diastolic dyssynchrony was highly prevalent in patients
      with aneurysm, irrespective of QRS duration. Aneurysm plication produces a
      mechanical intraventricular resynchronization.

PMID- 22613594
TI  - Pseudomembranous necrotizing tracheobronchial aspergillosis: an analysis of 16
      cases.
AB  - BACKGROUND: In our clinical practice we have been attracted by a group of
      patients with airway aspergillosis who have airway obstruction; we termed the
      condition as pseudomembranous necrotizing tracheobronchial aspergillosis (PNTA).
      In this study we analyzed the clinical data from patients with PNTA, so as to
      guide the diagnosis and treatment of the disease. METHODS: A total of 16 PNTA
      patients were treated in Changhai Hospital from January 2000 to January 2009.
      Their clinical data, including the demographic information, clinical symptoms,
      imaging findings, bronchoscopy findings, treatment strategies and efficacy, and
      prognosis, were retrospectively analyzed. RESULTS: All 16 patients were found to
      have primary systemic immunodeficiency diseases and/or damage of the focal
      airways. Nine patients (9/16, 56.3%) had pulmonary and tracheobronchial tumors,
      5/16 (31.3%) had tracheobronchial involvement secondary to non-pulmonary tumors,
      and 2/16 (12.5%) had lung transplantation. The most common causes of PNTA
      included local radiotherapy (10/16, 62.5%), repeated chemotherapy (7/16, 43.8%)
      and recurrent intervention therapy by bronchoscope (4/16, 25.0%). Aspergillus
      fumigatus was the most frequent pathogen (62.5%, 10/16). The main clinical
      manifestations included progressive dyspnea (14/16, 87.5%) and irritable cough
      (12/16, 75.0%). The trachea was involved in 9/16 patients (56.3%), right main
      bronchus in 10/16 (62.5%). All 16 patients were treated with systemic anti
      aspergillosis agents, local anti-aspergillosis agents with amphotericin B
      inhalation and direct perfusion of amphotericin B by bronchoscope, and
      interventional treatment by bronchoscope to ensure an unobstructed airway. The
      total efficiency was 31.3%. CONCLUSIONS: PNTA is an infectious disease caused by
      aspergillus and it mainly involves the trachea, primary bronchus and segmental
      bronchus. A. fumigatus is the most common pathogen. PNTA can pose a severe
      clinical threat and often occurs after systemic immunodeficiency and/or local
      airway damage, with the main symptoms including dyspnea and irritable cough.
      Bronchoscopic findings supply the main evidence for diagnosis of PNTA. Treatment
      of PNTA is difficult and requires a long course. Systemic and local anti
      aspergillosis agents plus bronchoscopy debridement can improve the prognosis of
      the disease.

PMID- 22613596
TI  - Relationship of plasminogen activator inhibitor 1 gene 4G/5G polymorphisms to
      hypertension in Korean women.
AB  - BACKGROUND: Hypertension (HTN) is a major determinant of various cardiovascular
      events. Plasma levels of plasminogen activator inhibitor 1 (PAI-1) modulate this
      risk. A deletion/insertion polymorphism within the PAI-1 loci (4G/4G, 4G/5G,
      5G/5G) affects the expression of this gene. The present study investigated the
      association between PAI-1 loci polymorphisms and HTN in Korean women. METHODS:
      Korean women (n = 1312) were enrolled in this study to evaluate the association
      between PAI-1 4G/5G gene polymorphisms and HTN as well as other metabolic risk
      factors. PAI-1 loci polymorphisms were investigated using polymerase chain
      reaction amplification and single-strand conformation polymorphism analysis.
      RESULTS: The three genotype groups differed with respect to systolic blood
      pressure (P = 0.043), and diastolic blood pressure (P = 0.009) but not with
      respect to age, body mass index, total cholesterol, low or high density
      lipoprotein cholesterol, triglycerides, or fasting blood glucose. Carriers of the
      PAI-1 4G allele had more hypertension significantly (PAI-1 4G/5G vs. PAI-1 5G/5G,
      P = 0.032; PAI-1 4G/4G vs. PAI-1 5G/5G, P = 0.034). When stratified according to
      PAI-1 4G/5G polymorphism, there was no significant difference in all metabolic
      parameters among PAI-1 genotype groups in patients with HTN as well as subjects
      with normal blood pressure. The estimated odds ratio of the 4G/4G genotype and
      4G/5G for HTN was 1.7 (P = 0.005), and 1.6 (P = 0.015), respectively. CONCLUSION:
      These findings might indicate that PAI-1 loci polymorphisms independently
      contribute to HTN and that gene-environmental interaction may be not associated
      in Korean women.

PMID- 22613597
TI  - Impact of surgery and epirubicin intravesical chemotherapy on peripheral blood
      dendritic cell subsets in patients with superficial urothelial carcinoma of the
      bladder.
AB  - BACKGROUND: Superficial urothelial carcinoma (SUC) of the bladder is a common
      urinary tract tumor in China. There is a high recurrence rate of this tumor even
      after surgery and intravesical instillation. Previous reports have described a
      suppression of the immune system in cancer patients. Dendritic cells (DCs) play a
      pivotal role in the induction of an effective antitumor immune response. The aim
      of this study was to investigate the effects of surgery and epirubicin
      intravesical chemotherapy (IC) on peripheral blood DCs in subsets of patients
      with bladder SUC. METHODS: A total of 66 SUC patients and 38 healthy controls
      were enrolled in this study. All the patients had undergone transurethral
      resection (TUR) of their cancer and adjunctive IC after tumor removal. The
      patients were divided into a non-recurrence group (n = 40) and a recurrence group
      (n = 26) based on the presence or absence of tumor recurrence. Blood samples were
      taken preoperatively (PreOP), on postoperative days (POD) 1 and 7, and at
      postoperative month (POM) 3. Flow cytometric analysis was used for the
      determination and quantitation of the surface markers CD80 and CD86 in
      circulating DC subsets. RESULTS: The preoperative percentages of myeloid
      dendritic cells (mDCs) and expression of CD80 and CD86 were impaired in SUC
      patients compared to healthy controls (P < 0.05). The percentages of mDCs and
      these surface markers decreased significantly on POD 1 and increased on POD 7,
      remaining higher than the preoperative values in POM 3 (P < 0.05). The
      percentages of mDCs, and CD80 and CD86 in the non-recurrence group on PreOP, POD
      7, and POM 3 were higher than those in recurrence group. CONCLUSIONS: Surgical
      removal of SUC and adjunctive IC were associated with improved circulating mDC
      counts and function. Persistent depression of mDC counts and function after
      treatment in recurrence patients indicated lower antitumor immunity that may lead
      to tumor recurrence.

PMID- 22613598
TI  - Clinical characteristics of hand, foot and mouth disease in Harbin and the
      prediction of severe cases.
AB  - BACKGROUND: Hand, foot and mouth disease (HFMD) is an emerging public health
      problem in China, not only threatening the health of children, but also causing
      tremendous loss and burden to both families and society. The aim of this study
      was to characterize the epidemiology and clinical features of HFMD, and to
      understand the key factors affecting HFMD in the Harbin region to provide
      scientific evidence for effective prevention and control strategies. METHODS:
      Epidemiological and clinical information from 2379 randomly chosen cases of HFMD
      treated at the Harbin Center for Disease Control and Prevention from May 2008 to
      November 2011 were analyzed. All cases were separated into common and severe
      HFMD, with key factors for severe HFMD analyzed using multivariable Logistic
      regression. RESULTS: Among the 2379 patients, 1798 were common cases and 581
      severe cases, 14 of which resulted in death. Most cases were in children younger
      than 5 years. Morbidity peaked in July and was higher in the surrounding country
      and cities than in Harbin proper. Medical expenses were significantly higher for
      severe than for common cases (P < 0.001). The primary clinical symptoms were
      fever and erythema; laboratory examination showed leucocytosis together with
      pneumonia, carditis, and abnormal electrocardiogram and electroencephalogram in
      severe cases. Multivariable Logistic regression analysis showed that the key
      factors for severe HFMD were age, morbidity location, morbidity area, fever
      duration, mouth mucosal symptoms, and abnormal serum levels of neutrophils
      (NEUT), hemoglobin and glucose (P < 0.05). CONCLUSIONS: To improve prognosis,
      reduce medical expense and prevent the development of severe cases, we should
      improve the epidemiological detection of HFMD to treat patients quickly. We
      should also closely monitor children with the EV71 virus, who present with
      continuous fever as well as abnormal laboratory results, from areas highly
      susceptible to HFMD attacks.

PMID- 22613599
TI  - Abnormal expression of CD43 in patients with systemic lupus erythematosus and its
      clinical significance.
AB  - BACKGROUND: Previous studies indicate that CD43 plays a role in regulating the
      adhesion of lymphocytes, cell mutation and activation, however, little is known
      about its effect on systemic lupus erythematosus (SLE). This study was designed
      to explore the clinical significance of CD43 in SLE patients. METHODS: We used
      microarray and real-time PCR to detect the mRNA and protein expression of
      magnetic bead sorted T cells and B cells from peripheral blood mononuclear cells
      (PBMCs) of SLE patients, and analyzed the relationship between CD43 and the
      clinical indexes. RESULTS: Both microarray and real-time PCR results showed that
      CD43 mRNA was significantly decreased in PBMCs of SLE patients compared with
      healthy controls (P < 0.001). There were no significant differences between lupus
      nephritis and non-lupus nephritis patients, and neuropsychiatric and non
      neuropsychiatric patients. CD43 mRNA expression was significantly reduced in T
      cells but not in B-cells in SLE patients compared to healthy controls (P < 0.01).
      Compared with healthy controls, the percentage of CD43(+) cells in the PBMCs of
      SLE was significantly decreased (P = 0.004), and the CD43 fluorescence intensity
      in CD3(+)/CD43(+) cells and CD19(+)/CD43(+) cells was also significantly weaker
      than in healthy controls (P = 0.039 and 0.003). There was no significant
      difference in the percentage of CD3(+)/CD43(+) cells, CD19(+)/CD43(+) cells
      between the two groups. The CD43 fluorescence intensity in CD3(+)/CD43(+) cells
      was inversely correlated with the levels of IgG and IgM (r = -0.8 and -0.6).
      CONCLUSIONS: Compared to healthy controls, both CD43 mRNA and protein expressions
      were reduced in T cells from patients with SLE, and were inversely correlated
      with IgG.

PMID- 22613600
TI  - Arthroscopic reduction and fixation for isolated greater tuberosity fractures.
AB  - BACKGROUND: Traditionally, displaced greater tuberosity fractures are treated
      with open reduction and internal fixation. Arthroscopic treatment and outcome of
      greater tuberosity fractures is far from comprehensive. The objective of the
      current study was to assess the surgical procedure and outcome of an arthroscopic
      method in the treatment of isolated greater tuberosity fractures. METHODS: From
      January 2006 to December 2009, 23 patients with isolated greater tuberosity
      fractures were treated with an arthroscopic procedure using three cannulated
      screws combined with washers. During follow-up, radiographs and the constant
      shoulder score (CSS) were used to evaluate the outcome. RESULTS: Three cannulated
      screws with washers were used to fix the fractured fragment of the greater
      tuberosity under an arthroscope. All incisions healed at primary intention
      without infection. The mean duration of follow-up was 20 months (range 18 - 36
      months). Fracture fixation was excellent, and fractures healed 2 - 6 months (mean
      3.8 months) after surgery. At final follow-up, the CSS was 92 (range 86 - 100).
      CONCLUSIONS: The described arthroscopic procedure provides anatomical reduction
      and firm fixation for isolated greater tuberosity fractures. It is a successful
      and minimally invasive procedure with satisfying therapeutic effects as well as
      excellent functional recovery.

PMID- 22613601
TI  - Assessment of middle ear effusion and audiological characteristics in young
      children with adenoid hypertrophy.
AB  - BACKGROUND: Otitis media with effusion is a highly concurrent disease in young
      children with adenoid hypertrophy. The aim of this study was to assess the middle
      ear effusion and audiological characteristics in children with adenoid
      hypertrophy and compare the various assessment methods. METHODS: Two hundred and
      seven candidates who were to undergo adenoidectomy were analyzed using otoscopy,
      tympanometry, air-conduction auditory steady-state responses (AC-ASSR), and
      computerized tomography (CT) before adenoidectomy. RESULTS: About 73.4% (304/414)
      of ears were confirmed to have middle ear effusion (MEE) by otoscopy; 75.4%
      (312/414) of ears revealed MEE by CT. CT scan correctly predicted all the
      myringotomy results, giving 100% accuracy on the diagnosis of MEE. Additionally,
      CT revealed two children with inner ear malformations. Type B tracing tympanogram
      provided a sensitivity of 91.7% and a specificity of 92.2%. Type C tympanogram
      with peak pressure < -200 daPa indicated effusion; type C tympanogram having
      acoustic stapedius reflex could exclude MEE. We excluded the AC-ASSR results of
      the 4 ears with malformation; 54.4% (223/410) of ears were confirmed of hearing
      loss. Furthermore, 5.2% (16/310) of the ears with MEE suffered from severe to
      profound hearing loss. The average threshold level in the 0.25 kHz frequency of
      children was found to have poorer hearing thresholds than those in the 0.5, 1, 2,
      and 4 kHz (P < 0.001) frequencies; 29.7% (92/310) of ears with MEE were regarded
      as normal hearing level. About 55.8% (173/310) of ears with MEE were classified
      as having slight-mild hearing loss. CONCLUSIONS: The practitioners should pay
      much attention to the middle ear condition and be aware of a possible development
      of severe to profound hearing loss during the course of MEE in young children
      with adenoid hypertrophy. CT scan is good for the assessment of MEE before
      ventilation tube insertion.

PMID- 22613602
TI  - Effect of high myopia on 24-hour intraocular pressure in patients with primary
      open-angle glaucoma.
AB  - BACKGROUND: As intraocular pressure (IOP) and IOP fluctuation are known risk
      factors for glaucoma, it is important to understand the effects of high myopia on
      these ocular parameters. The aim of this study was to investigate if primary open
      angle glaucoma (POAG) patients with high myopia exhibit higher IOP and greater
      IOP fluctuations at resting conditions over 24 hours. METHODS: We designed a
      prospective control clinical study. Eighty-two eyes of 82 high-tension Chinese
      POAG patients only on prostaglandin analogue locally were divided into 3 groups
      according to various myopic grades (< -6.0 D, n = 27 and between -0.76 and -5.99
      D, n = 33) or without myopia (-0.75 to 0.75 D, n = 22). Single time IOP at 10 am,
      mean corrected 24-hour IOP, mean corrected night IOP, 24-hour IOP fluctuation and
      IOPs of 10 am, 2 pm, 6 pm, 10 pm, 2 am, 6 am and 8 am were measured. RESULTS: The
      IOP was higher in POAG patients with high myopia over those POAG alone in three
      ways: the elevated IOP value was 0.65 mmHg measured in single time IOP at 10 am,
      0.84 mmHg in mean corrected 24-hour IOP, 0.97 mmHg in mean corrected night IOP.
      The 24-hour IOP fluctuation was lower in the two myopia groups than in non-myopia
      group. Further, using repeated measurement analysis of variance, there was no
      statistical significance among groups regarding the IOPs at the seven time points
      (P = 0.77) and there was no interaction between groups and time points (P =
      0.71), but the difference of IOPs at the seven time points in same group was
      statistically significant (P = 0.01). CONCLUSION: High-tension POAG patients with
      high myopia, even on pharmacological glaucoma therapy, still have higher IOP, but
      24-hour IOP fluctuation at resting conditions was lower in these patients.

PMID- 22613603
TI  - Practical value of intravenous urography combined with add-on CT in diagnosing
      ureteral abnormalities.
AB  - BACKGROUND: Intravenous urography (IVU) combined with add-on CT (IVU-CT) can help
      to provide more diagnostic information for determining the localization and
      nature of ureteral abnormalities with less irradiation dose. This study aimed to
      determine the value of IVU-CT for diagnosis of ureteral diseases, where IVU is
      insufficient to determine the diagnosis. METHODS: Two hundred and eighty patients
      underwent IVU for suspected ureteral disorders, which identified a definite
      diagnosis in 184 cases and was insufficient for definite diagnosis in 96 cases
      designated as indeterminate diagnosis. Subsequently 90 patients (six patients
      declined CT) with indeterminate diagnosis consented to undergo immediate or
      delayed helical CT scan. The CT data were transferred to the workstation for post
      processing, and the cost and mean effective dose for each imaging method were
      calculated and compared indirectly. RESULTS: Of the 90 indeterminate diagnosis
      cases, diagnosis was determined in 86 cases by IVU-CT with a diagnostic
      accordance rate of 95.6%, while 184/280 (65.7%) had diagnosis determined by IVU
      alone. There was a significant difference between IVU and IVU-CT in the
      determination of the diagnosis of ureteral diseases (c(2) = 36.4, P < 0.05). The
      cost of IVU equals to 1/8 - 1/9 of that for CT urography (CTU), and the cost of
      IVU-CT is as much as 1/3 of CTU. CTU results in the highest mean effective dose,
      approximately nine times that for IVU and three times that for IVU-CT.
      CONCLUSION: IVU-CT provides valuable information for the localization and
      diagnosis of ureteral abnormalities and may be considered as an efficient, cost
      effective and low-dose diagnostic technique in this setting.

PMID- 22613604
TI  - Experimental study on neuroendocrinological and immunological characteristics of
      the military-trained artillerymen.
AB  - BACKGROUND: Over one million soldiers were treated for battle- or training
      fatigue during World War II. Of all ground combat troops, 37% were discharged for
      psychiatric reasons due to fatigue. The neuroendocrinological and immunological
      systems played important roles in the work-related fatigue of military personnel.
      The aim of this study was to investigate the characteristics of fatigue
      associated with military operations, and we observed changes in the regulatory
      functions of the neuroendocrinological and immunological systems that may provide
      theoretical support for improving the combat effectiveness of armies. METHODS: A
      total of 240 soldiers from the Field Artillery regiment were selected as
      subjects. Researchers and subjects received training before participating in the
      study. Data of the subjects' medical histories, physical examinations, scores on
      a fatigue assessment scale, and assessments of pituitary-adrenal hormones
      (adrenal cortical hormone (ACTH), cortical hormone (F), and 24-hour urine-free
      cortisol (UFC)), pituitary-gonadal hormones (luteinizing hormone (LH), follicle
      stimulating hormone (FSH), testosterone, estradiol (E2), and prolactin (PRL)),
      pituitary-thyroid hormones (thyroid-stimulating hormone (TSH), thyroxine (TT4),
      triiodothyronine (TT3), free thyroxine (FT4), and free triiodothyronine (FT3)),
      and cellular immune parameters (CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+), B, and NK
      cells) were investigated before and after large-scale and high-intensity field
      exercises. Data were statistically analyzed with Student's t test using SPSS
      software (version 13.0), and P values < 0.05 were deemed to be significant.
      RESULTS: After the high-intensity military training, the scores on the fatigue
      scale reflected significant increases of feeling of unpleasantness among
      soldiers. Additionally, the symptom checklist showed notable increases in
      somatization scores and significant decreases in psychoticism scores. After
      intensive military work, levels of plasma ACTH, F, and UFC of soldiers were
      decreased (P < 0.01). The level of testosterone decreased significantly after the
      maneuver ((23.51 +/- 6.49) versus (18.89 +/- 5.89) nmol/L; P < 0.001), whereas
      the thyroid function (TT3, FT4, and FT3) was markedly increased after the
      maneuver (P < 0.01). The number of CD3(+), CD4(+), CD4(+)/CD8(+) cells, and B
      lymphocytes were decreased (P < 0.05), and NK cells were increased (P < 0.001)
      after the maneuver. CONCLUSIONS: Following high-intensity military operations,
      the psychological tolerance of soldiers was depressed. And the
      hypoadrenocorticism (the functional decreases of hypothalamic-pituitary-gonadal
      and abnormal pituitary-thyroid axis) contributed to the increased levels of
      fatigue. Hypoimmunity may increase the susceptibility to diseases after high
      intensity military operations.

PMID- 22613605
TI  - Strong halo-femoral traction with wide posterior spinal release and three
      dimensional spinal correction for the treatment of severe adolescent idiopathic
      scoliosis.
AB  - BACKGROUND: Many investigators advocate anterior release combined with halo
      femoral traction and posterior fusion when treating stiff thoracic curves in
      patient with adolescent idiopathic scoliosis (AIS). But the anterior operations
      often induce severe complications. Some surgeons choose posterior-only surgery
      with halo-femoral traction, posterior wide release and correction. But to the
      best of our knowledge, there are only rare prospective studies on these posterior
      only surgeries for AIS patients who have a rigid curve more than 80 degrees  and
      flexibility less than 35%. METHODS: Sixty-four AIS patients were recruited from
      September 2006 to June 2009. All patients had rigid curves and underwent spinal
      correction. They were randomly divided into group A (combined anteroposterior
      surgery) and group B (posterior-only surgery). Images and scoliosis research
      society-22 questionnaire (SRS-22) scores were performed pre- and post-operation
      and during follow-up visits. The operation time, blood loss, hospital days, and
      hospital charges were compared between the two groups. RESULTS: These patients
      were followed for an average of 37.5 months (range, 24 - 65 months). No serious
      complications were observed. There were no significant differences between the
      two groups in gender, age, preoperative radiographic data, or preoperative SRS-22
      score. The average operation time, blood loss, hospital days and hospital charges
      in group B were less than those in group A. The SRS-22 score in group B was
      better than in group A at post-operation and at final follow-up. CONCLUSIONS: In
      AIS with a rigid curve more than 80 degrees  and flexibility less than 35%,
      strong halo-femoral traction with wide posterior spinal release and three
      dimensional spinal correction can provide better SRS-22 scores, comparable curve
      correction, shorter operation time, less blood loss, shorter hospital stays and
      lower charges when compared to combined anterior and posterior surgery.

PMID- 22613606
TI  - Biological characteristics of the cerebral venous system and its hemodynamic
      response to intracranial hypertension.
AB  - BACKGROUND: The role of the cerebral venous system (CVS) in intracranial pressure
      (ICP) regulation remains largely unclear. In the present study, the interaction
      between ICP and the cerebral venous system and its possible mechanism were
      investigated with respect to the biological characteristics of the cerebral
      venous system and its hemodynamic response under increased ICP. METHODS: We
      created intracranial hypertension animal model, measured and calculated the
      venous flow velocity and diameter of the outflow terminal of the CVS with color
      ultrasonic system and recorded the vascular morphology by 3-dimensional
      anatomical microscopy. Patients who suffered from raised ICP underwent MRI and
      digital subtraction angiography (DSA) examination to show the length in the
      vertical direction of the wall of the bridging vein representing the diameter
      value. Pathological autopsy was performed from bodies of patients who had died
      from non-cerebral causes to observe the juncture part between the venous sinuses
      and tributary vertical brain veins. RESULTS: Under increased ICP conditions,
      venous drainage through the outlet cuff segment, a unique structure between the
      bridge vein and sinus, was obstructed and in turn venous blood became congested.
      Therefore, the increased blood volume worsened the pre-existing ICP according to
      the well-accepted theory regarding volume-pressure relationship. This phenomenon
      was described as concurrent "venogenic intracranial hypertension", which is
      characterized by intracranial venous blood stasis responsive to and together with
      the original increased ICP. CONCLUSIONS: The existence of this special
      pathophysiological process is prevalent, rather than rare, in various
      intracranial disorders. This finding would definitely provide new insight into
      the area of cerebral venous system research.

PMID- 22613607
TI  - Activity of heme oxygenase-1 affects expression levels of hypoxia inducible
      factor-1 gene in vitro.
AB  - BACKGROUND: One effect of solid tumors is severe hypoxia of local tissues. Heme
      oxygenase-1 (HO-1) is highly expressed in a variety of human tumor tissues; its
      induction and activity are closely related to growth of solid tumors. Hypoxia
      inducible factor-1 (HIF-1) is a transcription factor that regulates hypoxia
      signal transduction and plays a central role in tumor hypoxia regulation.
      However, whether and how changes in HO-1 activity affect HIF-1 gene expression
      has not been reported previously. METHODS: Hypoxia-inducible models were
      established using gastric cancer cell lines (SGC-7901) in a hypoxia incubator.
      Cells were placed in four groups: Group A, transfected by plasmid harboring HO-1
      shRNA; Group B, transfected with scrambled shRNA vector; Group C, treated with
      hemin; and Group D, exposed to hypoxia only. Expressions of HO-1 and HIF-1 mRNAs
      were quantified by reverse transcription-polymerase chain reaction. Expressions
      of HO-1 and HIF-1 proteins were determined by immunohistochemistry and Western
      blotting. RESULTS: mRNA and protein levels of HO-1 and HIF-1 in the control group
      were significantly higher than in Group A (P < 0.01), but lower than in Group C
      (P < 0.01). Chromatin immunoprecipitation analysis showed that HIF-1 was
      identified as the direct HO-1 target gene. CONCLUSION: While affected by HIF-1,
      HO-1 up-regulation promotes the expression of HIF-1 and the down-regulation of HO
      1 suppresses the expression of HIF-1 gene.

PMID- 22613608
TI  - Inside out transobturator vaginal tape versus tention-free vaginal tape for
      primary female stress urinary incontinence: meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: Inside out transobturator vaginal tape (TVT-O) and tension-free
      vaginal tape (TVT) are predominant surgical treatments for female stress urinary
      incontinence. This meta-analysis evaluated the complications and cure rates of
      TVT-O versus TVT. METHODS: A comprehensive literature search was conducted
      according to the Cochrane Collaboration methodology to identify randomized
      controlled clinical trials with no language restriction. Two authors
      independently assessed papers for eligibility and methodological quality.
      Estimates were measured by relative risk with 95% confidence intervals. Outcome
      measures were objective cure, subjective cure and complications. Quality rating
      for each outcome of the meta-analysis and recommendations were performed by the
      Grading of Recommendations Assessment, Development, and Evaluation (GRADE)
      system. RESULTS: Twenty randomized controlled trials met the inclusion criteria,
      and a pooled estimate of effectiveness and complications was made. Relative risks
      with 95% confidence intervals for pooled effects under the fixed effects model
      were: 0.20 (0.09 - 0.45), for bladder injury, 0.37 (0.16 - 0.86) for hematoma,
      and 2.35 (1.57 - 3.51) for postoperative pain, suggesting an 80% risk reduction
      of bladder injury, 63% risk reduction of hematoma, and a 1.35% risk elevation for
      postoperative pain with TVT-O. There was no significant difference between
      complications of urinary tract infection 1.14 (0.78 - 1.65), lower urinary tract
      symptoms 1.60 (0.67 - 3.79), recatheterization 0.93 (0.59 - 1.44), and tape
      erosion 0.90 (0.48 - 1.67), total objective cure rate 1.06 (0.39 - 2.84) and for
      the subjective cure rate 0.98 (0.93 - 1.04). The quality rating for each outcome
      and recommendations was high for objective cure, bladder injury, hematoma, lower
      urinary tract symptoms, and tape erosion and moderate for subjective cure, pain,
      and urinary tract infection. CONCLUSIONS: TVT-O is associated with a reduced risk
      of bladder injury and hematoma and an elevated risk of postoperative pain. Other
      complications, including tape erosion, urinary tract infection, lower urinary
      tract symptoms, and recatheterization, are similar to those of TVT.

PMID- 22613609
TI  - Progress in studies on the role of gamma-aminobutyric acid.

PMID- 22613610
TI  - New policies and strategies to tackle HIV/AIDS in China.

PMID- 22613611
TI  - Evaluation of 3-day smoking cessation training course for doctors from 38 cities
      in China.
AB  - BACKGROUND: The World Health Organization's "Framework Convention on Tobacco
      Control" came into effect in China in 2006. Since then, a series of tobacco
      control measures has been undertaken, including the first step to establish a
      coordinated network of stop-smoking clinics in Chinese hospitals. Training for
      stop-smoking specialists has been traditionally provided via printed materials.
      This study evaluated the outcomes of the first two intensive 3-day courses in
      smoking cessation in China run in collaboration with experts who provide training
      to UK Specialist Stop Smoking Service. METHODS: Eighty-four doctors from 38
      cities in China responsible for stop-smoking treatment in 20 provinces and four
      autonomous regions participated in the training courses. Participants' knowledge
      competencies and self-efficacy were assessed before and after the authentication
      training. RESULTS: The training significantly improved participants' knowledge,
      skills and self-efficacy across different domains. Forty-eight participants were
      finally certified as "smoking cessation specialist". CONCLUSIONS: The UK model of
      face-to-face training was acceptable and effective in China. A relatively brief
      intensive training program can generate significant improvements in skills,
      knowledge, and readiness to engage in smoking cessation activities.

PMID- 22613612
TI  - Expectant management of heterotopic cesarean scar pregnancy.
AB  - BACKGROUND: Heterotopic cesarean scar pregnancy (HCSP) is a very rare but life
      threatening entity and there is no optimal management strategy. Here we report a
      successfully managed case of HCSP with expectant treatment in a tertiary referral
      hospital. METHODS: A woman with HCSP after in vitro fertilization-embryo transfer
      opted for expectant treatment after five days of mild bleeding and ultrasound
      demonstrated cardiac activity disappearance of the scar pregnancy at 8(+4) weeks
      of gestation. RESULTS: The patient had mild to moderate bleeding during close
      monitoring. Three days later, speculum examination revealed the gestational mass
      was partly protruding at the os of the cervix and it was removed with forceps
      without massive hemorrhage. A healthy male baby was delivered by cesarean section
      at gestational age of 36(+4) weeks. CONCLUSIONS: The expectant method might be an
      alternative option for a HCSP with loss of cardiac activity of the scar
      pregnancy, when applied under supportive management and with available emergency
      surgery facilities.

PMID- 22613613
TI  - Efficacy of local aspiration in the conservative treatment of live interstitial
      pregnancy coexisting with live intrauterine pregnancy after in vitro
      fertilization and embryo transfer.
AB  - BACKGROUND: Heterotopic pregnancy (HP) is defined as a pregnancy in which one or
      more embryos is viably implanted in the uterus while the other is implanted
      elsewhere as an ectopic pregnancy. The occurrence of HP rises dramatically with
      the increased use of assisted reproductive technology. HP of interstitial
      pregnancy is one special situation which needs more concern. Here we evaluate the
      efficacy of local aspiration and instillation of hyperosmolar glucose in the
      treatment of live interstitial pregnancy complicated with live intrauterine
      pregnancy after in vitro fertilization and embryo transfer. METHODS: Five female
      patients were diagnosed with live interstitial pregnancies complicated with
      intrauterine pregnancies. They were treated with transvaginal ultrasound-guided
      aspiration of interstitial pregnancy and instillation of hyperosmolar glucose at
      the Center for Reproductive Medicine of Peking University Third Hospital from
      January 1st, 2008 to May 30th, 2011. RESULTS: Gemmule embryos in all 5 cases were
      aspirated successfully and there was no abdominal hemorrhage, threatened abortion
      or infection in any of the cases. The sac of interstitial pregnancy continued to
      progress after aspiration and stopped growing between 11 to 20 weeks. By the 30th
      week of pregnancy, 80% of the interstitial masses had disappeared. Four cases
      have delivered and one is still in on-going pregnancy. All of the four cases
      underwent cesarean section and there were nothing special detected in the corner
      of the uterus. CONCLUSION: Local aspiration and instillation of hyperosmolar
      glucose may be an effective way to treat live interstitial pregnancy when
      coexisting with a live intrauterine pregnancy.

PMID- 22613614
TI  - A case report on the relationship between treatment-resistant childhood-onset
      schizophrenia and an abnormally enlarged cavum septum pellucidum combined with
      cavum vergae.
AB  - The treatment of refractory schizophrenia has been a clinical challenge for most
      psychiatrists; the possible reasons include diagnostic errors, medical conditions
      and brain dysgenesis. Here, we described a patient with childhood-onset
      schizophrenia who had severe psychiatric symptoms such as auditory hallucinations
      and persecutory delusions, and etc. We reexamined all his possible medical
      conditions and found that the patient had an abnormally enlarged cavus septum
      pellucidum (CSP) combined with cavum vergae (CV) (maximum length >30 mm). Some
      reports suggested that abnormal CSP (length >6 mm) has a significant association
      with schizophrenia. However, abnormally large CSP or CSP/CV and related prognosis
      were reported rarely. This case suggested that abnormally enlarged CSP or CSP/CV
      may worsen the prognosis.

PMID- 22613615
TI  - Tacrolimus-related hypertrophic cardiomyopathy in an adult cardiac transplant
      patient.
AB  - Left ventricular hypertrophy associated with the use of tacrolimus is a rare
      complication of solid organ transplantation in adult recipients. We present a
      cardiac transplant recipient who developed severe concentric left ventricular
      hypertrophy with congestive heart failure related to myocardial hypertrophy on
      tacrolimus. Hypertrophy improved when the drug was discontinued and replaced with
      sirolimus.

PMID- 22613616
TI  - Intrahepatic biliary cystadenoma presenting with pleural effusion.
AB  - Hepatobiliary cystadenomas are rare cystic neoplasms that often occur in middle
      aged women. The exact etiology of these tumors is unknown. Diagnosis is often
      delayed in these cases. However, misdiagnosis and inappropriate treatment may
      result in unfavorable outcome. We report a case of hepatobiliary cystadenoma with
      pleural effusion. We also review the literature and discuss the current
      diagnostic and treatment modalities.

PMID- 22613617
TI  - A type IV osteogenesis imperfecta family and pregnancy: a case report and
      literature review.
AB  - Osteogenesis imperfecta is a group of inherited connective-tissue disorders in
      which synthesis or structure of type I collagen is defective and causes osseous
      fragility. Type IV osteogenesis imperfecta is dominant inheritance. Here, we
      report a case of type IV osteogenesis imperfecta family and their female member's
      pregnancy. Abnormal sonographic findings (marked bowing and shortening of long
      bones) and family history made the diagnosis of fetus with osteogenesis
      imperfecta. The parents decided to give up rescuing the infant and a caesarean
      section at 27 weeks of gestation was implemented. In conclusion, it is possible
      to make a prenatal diagnosis of osteogenesis imperfecta by ultrasound. For the
      pregnant women with osteogenesis imperfecta, management decision should be made
      on an individual basis.

PMID- 22613618
TI  - N-glycosylation promotes the cell surface expression of Kv1.3 potassium channels.
AB  - The voltage-gated potassium channel Kv1.3 plays an essential role in modulating
      membrane excitability in many cell types. Kv1.3 is a heavily glycosylated
      membrane protein. Two successive N-glycosylation consensus sites, N228NS and
      N229ST, are present on the S1-S2 linker of rat Kv1.3. Our data suggest that Kv1.3
      contains only one N-glycan and it is predominantly attached to N229 in the S1-S2
      extracellular linker. Preventing N-glycosylation of Kv1.3 significantly decreased
      its surface protein level and surface conductance density level, which were ~ 49%
      and ~ 46% respectively of the level of wild type. Supplementation of N
      acetylglucosamine (GlcNAc), l-fucose or N-acetylneuraminic acid to the culture
      medium promoted Kv1.3 surface protein expression, whereas supplementation of d
      glucose, d-mannose or d-galactose did not. Among the three effective
      monosaccharides/derivatives, adding GlcNAc appeared to reduce sialic acid content
      and increase the degree of branching in the N-glycan of Kv1.3, suggesting that
      the N-glycan structure and composition had changed. Furthermore, the cell surface
      half-life of the Kv1.3 surface protein was increased upon GlcNAc supplementation,
      indicating that it had decreased internalization. The GlcNAc effect appears to
      apply mainly to membrane proteins containing complex type N-glycans. Thus, N
      glycosylation promotes Kv1.3 cell surface expression; supplementation of GlcNAc
      increased Kv1.3 surface protein level and decreased its internalization,
      presumably by a combined effect of decreased branch size and increased branching
      of the N-glycan.

PMID- 22613619
TI  - Acute exposure to the mitochondrial complex I toxin rotenone impairs synaptic
      long-term potentiation in rat hippocampal slices.
AB  - AIMS: To evaluate the acute effects of the mitochondrial complex I inhibitor
      rotenone on rat hippocampal synaptic plasticity. METHODS: Electrophysiological
      field potential recordings were used to measure basal synaptic transmission and
      synaptic plasticity in rat coronal hippocampal slices. Synaptic long-term
      potentiation (LTP) was induced by high-frequency stimulation (100 Hz, 1 second *
      3 at an interval of 20 seconds). In addition, mitochondrial complex I function
      was measured using MitoSOX imaging in mitochondrial preparations. RESULTS: Acute
      exposure of hippocampal slices to 50 nM rotenone for 1 h did not alter basal CA3
      CA1 synaptic transmission though 500 nM rotenone significantly reduced basal
      synaptic transmission. However, 50 nM rotenone significantly impaired LTP and
      this rotenone's effect was prevented by co-application of rotenone plus the
      ketones acetoacetate and beta-hydroxybutyrate (1 mM each). Finally, we measured
      mitochondrial function using MitoSOX imaging in mitochondrial preparations and
      found that 50 nM rotenone partially reduced mitochondrial function whereas 500 nM
      rotenone completely eliminated mitochondrial function. CONCLUSIONS: Our findings
      suggest that mitochondrial activity driven by complex I is a sensitive modulator
      of synaptic plasticity in the hippocampus. Acute exposure of the hippocampus to
      rotenone eliminates complex I function and in turn impairs LTP.

PMID- 22613620
TI  - Altered structural connectivity in neonates at genetic risk for schizophrenia: a
      combined study using morphological and white matter networks.
AB  - Recently, an increasing body of evidence suggests that developmental
      abnormalities related to schizophrenia may occur as early as the neonatal stage.
      Impairments of brain gray matter and wiring problems of axonal fibers are
      commonly suspected to be responsible for the disconnection hypothesis in
      schizophrenia adults, but significantly less is known in neonates. In this study,
      we investigated 26 neonates who were at genetic risk for schizophrenia and 26
      demographically matched healthy neonates using both morphological and white
      matter networks to examine possible brain connectivity abnormalities. The results
      showed that both populations exhibited small-world network topology.
      Morphological network analysis indicated that the brain structural associations
      of the high-risk neonates tended to have globally lower efficiency, longer
      connection distance, and less number of hub nodes and edges with relatively
      higher betweenness. Subgroup analysis showed that male neonates were
      significantly disease-affected, while the female neonates were not. White matter
      network analysis, however, showed that the fiber networks were globally
      unaffected, although several subcortical-cortical connections had significantly
      less number of fibers in high-risk neonates. This study provides new lines of
      evidence in support of the disconnection hypothesis, reinforcing the notion that
      the genetic risk of schizophrenia induces alterations in both gray matter
      structural associations and white matter connectivity.

PMID- 22613621
TI  - Sonoluminescence and sonochemiluminescence from a microreactor.
AB  - Micromachined pits on a substrate can be used to nucleate and stabilize
      microbubbles in a liquid exposed to an ultrasonic field. Under suitable
      conditions, the collapse of these bubbles can result in light emission
      (sonoluminescence, SL). Hydroxyl radicals (OH()) generated during bubble collapse
      can react with luminol to produce light (sonochemiluminescence, SCL). SL and SCL
      intensities were recorded for several regimes related to the pressure amplitude
      (low and high acoustic power levels) at a given ultrasonic frequency (200kHz) for
      pure water, and aqueous luminol and propanol solutions. Various arrangements of
      pits were studied, with the number of pits ranging from no pits (comparable to a
      classic ultrasound reactor), to three-pits. Where there was more than one pit
      present, in the high pressure regime the ejected microbubbles combined into
      linear (two-pits) or triangular (three-pits) bubble clouds (streamers). In all
      situations where a pit was present on the substrate, the SL was intensified and
      increased with the number of pits at both low and high power levels. For imaging
      SL emitting regions, Argon (Ar) saturated water was used under similar
      conditions. SL emission from aqueous propanol solution (50mM) provided evidence
      of transient bubble cavitation. Solutions containing 0.1mM luminol were also used
      to demonstrate the radical production by attaining the SCL emission regions.

PMID- 22613622
TI  - Which Therapy for Helicobacter pylori Infection?

PMID- 22613623
TI  - In vitro expansion and transplantation of intestinal crypt stem cells.

PMID- 22613624
TI  - Molecularly engineered islet cell clusters for diabetes mellitus treatment.
AB  - Pancreatic islet transplantation is a promising method for curing diabetes
      mellitus. We proposed in this study a molecularly engineered islet cell clusters
      (ICCs) that could overcome problems posed by islet transplantation circumstances
      and host's immune reactions. A gene containing  highly releasable exendin-4, an
      insulinotropic protein, was delivered into single islet cells to enhance glucose
      sensitivity; thereafter, the cells were reaggregated into small size ICCs. Then
      the surface of ICCs was modified with biocompatible poly(ethylene glycol)-lipid
      (PEG) (C18) for preventing  immune reactions. The regimen of ICCs with low doses
      of anti-CD154 mAb and tacrolimus could effectively maintain the normal glucose
      level in diabetic mice. This molecularly engineered PEG-Sp-Ex-4 ICC regimen
      prevented cell death in transplantation site, partly through improving the
      regulation  of glucose metabolism and by preventing hypoxia- and immune response
      induced apoptosis. Application of this remedy is also potentially far-reaching;
      one would be to help overcome islet supply shortage due to the limited
      availability of pancreas donors and reduce the immunosuppressant regimens  to
      eliminate their adverse effects.

PMID- 22613626
TI  - Interaction forces between a deformable air bubble and a spherical particle of
      tuneable hydrophobicity and surface charge in aqueous solutions.
AB  - Interaction forces between an air bubble and a spherical particle of moderate and
      tuneable surface charge density and hydrophobicity in aqueous solutions were
      measured using atomic force microscopy. Bitumen coated silica spheres were used
      as model particles of tuneable charge density and hydrophobicity due to pH
      dependent ionisation of carboxylic acids at bitumen-water interfaces. The
      measured force profiles showed a long-range repulsion prior to jump into contact,
      indicating the rupture of intervening liquid film between the bitumen and bubble
      surfaces. The long-range repulsive force increased with increasing pH. The
      measured force profiles were analysed by adopting the model originally developed
      by White and co-workers to account for deformation and change in shape of bubbles
      before rupture of the intervening liquid film. Satisfactory agreement between the
      theory and measured force profiles was obtained, showing the suitability of the
      model to describe the measured interaction forces. The model was then used to
      study the physical parameters on the particle-bubble interaction forces prior to
      three phase contact line (TPCL) formation. The hydrophobic decay length, surface
      potential and size of bubble and probe particles, and ionic strength of the
      medium (KCl concentration) were found to have a strong influence on the predicted
      force profiles.

PMID- 22613625
TI  - Enhanced antitumoral efficacy and immune response following conditionally
      replicative adenovirus containing constitutive HSF1 delivery to rodent tumors.
AB  - BACKGROUND: Oncolytic adenoviruses are promising as anticancer agents but have
      limited clinical responses. Our previous study showed that heat shock
      transcription factor 1 (HSF1) overexpression could increase the anti-tumor
      efficacy of E1B55kD deleted oncolytic adenovirus through increasing the viral
      burst. Due to the important roles of heat shock proteins (HSPs) in eliciting
      innate and adaptive immunity, we reasoned that besides increasing the viral
      burst, HSF1 may also play a role in increasing tumor specific immune response.
      METHODS: In the present study, intra-dermal murine models of melanoma (B16) and
      colorectal carcinoma (CT26) were treated with E1B55kD deleted oncolytic
      adenovirus Adel55 or Adel55 incorporated with cHSF1, HSF1i, HSP70, or HSP90 by
      intra-tumoral injection. Tumors were surgically excised 72 h post injection and
      animals were analyzed for tumor resistance and survival rate. RESULTS:
      Approximately 95% of animals in the Adel55-cHSF1 treated group showed sustained
      resistance upon re-challenge with autologous tumor cells, but not in PBS, Adel55,
      or Adel55-HSF1i treated groups. Only 50-65% animals in the Adel55-HSP70 and
      Adel55-HSP90 treated group showed tumor resistance. Tumor resistance was
      associated with development of tumor type specific cellular immune responses.
      Adel55-cHSF1 treatment also showed higher efficacy in diminishing progression of
      the secondary tumor focus than Adel55-HSP70 or Adel55-HSP90 treatment.
      CONCLUSIONS: Besides by increasing its burst in tumor cells, cHSF1 could also
      augment the potential of E1B55kD deleted oncolytic adenovirus by increasing the
      tumor-specific immune response, which is beneficial to prevent tumor recurrence.
      cHSF1 is a better gene for neoadjuvant immunotherapy than other heat shock
      protein genes.

PMID- 22613627
TI  - Synthesis and characterization of multifunctional Fe3O4/poly(fluorescein O
      methacrylate) core/shell nanoparticles.
AB  - Multifunctional fluorescent and superparamagnetic Fe(3)O(4)/poly(fluorescein O
      methacrylate) [Fe(3)O(4)/poly(FMA)] nanoparticles with core/shell structure were
      synthesized via surface-initiated polymerization. First, polymerizable double
      bonds were introduced onto the surface of Fe(3)O(4) nanoparticles via ligand
      exchange and a condensation reaction. A fluorescent monomer, FMA, was then
      polymerized to the double bonds at the surface via free-radical polymerization,
      leading to form a fluorescent polymer shell around the superparamagnetic
      Fe(3)O(4) core. The resultant Fe(3)O(4)/poly(FMA) nanoparticles were
      characterized by Fourier transform infrared, nuclear magnetic resonance, and X
      ray diffraction spectroscopy to confirm the reactions. Transmission electron
      microscopy images showed that the Fe(3)O(4)/poly(FMA) nanoparticles have a
      spherical and monodisperse core/shell morphology. Photoluminescence spectroscopy
      and superconducting quantum interference device magnetometer analyses confirmed
      that the Fe(3)O(4)/poly(FMA) nanoparticles exhibited fluorescent and
      superparamagnetic properties, respectively. In addition, we demonstrated the
      potential bioimaging application of the Fe(3)O(4)/poly(FMA) nanoparticles by
      visualizing the cellular uptake of the nanoparticles into A549 lung cancer cells.

PMID- 22613628
TI  - Unusual cause of myocardial ischemia in an infant.
AB  - Abnormal coronary artery anatomy should be ruled out in any patient with
      myocardial dysfunction and an abnormal electrocardiogram. The reported etiologies
      of infantile myocardial ischemia are abnormalities of coronary arteries,
      perinatal asphyxia, umbilical catheterization, and myocarditis. Generalized
      arterial calcification of infancy, although rare, should be considered in the
      differential diagnosis of infantile myocardial ischemia if coronary artery origin
      is found to be normal on echocardiography.

PMID- 22613629
TI  - Neural basis of a multidimensional model of body image distortion in anorexia
      nervosa.
AB  - Body image distortion is a key symptom of anorexia nervosa (AN). The majority of
      the neuroimaging studies on body image distortion in AN conceptualized it as an
      unidimensional symptom. However, behavioural research considers such symptom as a
      multidimensional construct. Our paper systematically reviews the functional
      magnetic resonance (fMRI) studies on body image distortion in AN and classifies
      them according to a speculative model of body image distortion, that consists of
      the three most widely accepted components in the behavioural research:
      perceptive, affective and cognitive. We found that: (1) the perceptive component
      is mainly related to alterations of the precuneus and the inferior parietal lobe;
      (2) the affective component is mainly related to alterations of the prefrontal
      cortex, the insula and the amygdala; (3) the cognitive component has been weakly
      explored. These evidences seem to confirm that specific neural alterations are
      related to the components of the body image distortion in AN. Further
      neuroimaging studies are needed to better understand the complexity of the body
      image distortion in AN.

PMID- 22613631
TI  - [Recurrent syncope secondary to intestinal invagination].

PMID- 22613630
TI  - odd-skipped genes and lines organize the notum anterior-posterior axis using
      autonomous and non-autonomous mechanisms.
AB  - The growth and patterning of Drosophila wing and notum primordia depend on their
      subdivision into progressively smaller domains by secreted signals that emanate
      from localized sources termed organizers. While the mechanisms that organize the
      wing primordium have been studied extensively, those that organize the notum are
      incompletely understood. The genes odd-skipped (odd), drumstick (drm), sob, and
      bowl comprise the odd-skipped family of C(2)H(2) zinc finger genes, which has
      been implicated in notum growth and patterning. Here we show that drm, Bowl, and
      eyegone (eyg), a gene required for notum patterning, accumulate in nested domains
      in the anterior notum. Ectopic drm organized the nested expression of these
      anterior notum genes and downregulated the expression of posterior notum genes.
      The cell-autonomous induction of Bowl and Eyg required bowl, while the non
      autonomous effects were independent of bowl. The homeodomain protein Bar is
      expressed along the anterior border of the notum adjacent to cells expressing the
      Notch (N) ligand Delta (Dl). bowl was required to promote Bar and repress Dl
      expression to pattern the anterior notum in a cell-autonomous manner, while lines
      acted antagonistically to bowl posterior to the Bowl domain. Our data suggest
      that the odd-skipped genes act at the anterior notum border to organize the notum
      anterior-posterior (AP) axis using both autonomous and non-autonomous mechanisms.

PMID- 22613632
TI  - Neck injury response to direct head impact.
AB  - Previous in vivo studies have observed flexion of the upper or upper/middle
      cervical spine and extension at inferior spinal levels due to direct head
      impacts. These studies hypothesized that hyperflexion may contribute to injury of
      the upper or middle cervical spine during real-life head impact. Our objectives
      were to determine the cervical spine injury response to direct head impact,
      document injuries, and compare our results with previously reported in vivo data.
      Our model consisted of a human cadaver neck (n=6) mounted to the torso of a rear
      impact dummy and carrying a surrogate head. Rearward force was applied to the
      model's forehead using a cable and pulley system and free-falling mass of 3.6kg
      followed by 16.7kg. High-speed digital cameras tracked head, vertebral, and
      pelvic motions. Average peak spinal rotations observed during impact were
      statistically compared (P<0.05) to physiological ranges obtained from intact
      flexibility tests. Peak head impact force was 249 and 504N for the 3.6 and 16.7kg
      free-falling masses, respectively. Occipital condyle loads reached 205.3N
      posterior shear, 331.4N compression, and 7.4Nm extension moment. We observed
      significant increases in intervertebral extension peaks above physiologic at C6/7
      (26.3 degrees  vs. 5.7 degrees ) and C7/T1 (29.7 degrees  vs. 4.6 degrees ) and
      macroscopic ligamentous and osseous injuries at C6 through T1 due to the 504N
      impacts. Our results indicate that a rearward head shear force causes complex
      neck loads of posterior shear, compression, and extension moment sufficient to
      injure the lower cervical spine. Real-life neck injuries due to motor vehicle
      crashes, sports impacts, or falls are likely due to combined loads transferred to
      the neck by direct head impact and torso inertial loads.

PMID- 22613633
TI  - A patient with ulcerated calcifying epithelioma of Malherbe in the pinna: case
      report.
AB  - INTRODUCTION: Although pilomatrixomas are frequently encountered by
      dermatologists and pathologists in the differential diagnosis of head and neck
      lesions, this is not usually the case among head and neck surgeons. A
      pilomatrixoma (calcifying epithelioma of Malherbe) is a benign tumour of the hair
      matrix cells. Histologically it is characterised by the presence of ghost cells,
      basophilic cells and foreign body cells. It may sometimes be difficult to
      histologically distinguish it from its malignant counterpart, the pilomatrix
      carcinoma. We report an interesting case of an ulcerated pilomatrixoma of the
      pinna in a middle-aged Caucasian female. CASE PRESENTATION: A 46-year-old
      Caucasian female presented with a one-month history of tender brownish lump on
      the pinna. Initially it was thought to represent a pyogenic granuloma. The lesion
      was treated by wide circular excision. Histopathological evaluation reported a
      benign calcifying epithelioma of Malherbe. CONCLUSION: A search of the world's
      literature has led us to believe that this is a rare case of a calcifying
      epithelioma of Malherbe of the pinna. The rapid growth and ulcerative nature of
      this tumour makes this case even more unique.

PMID- 22613634
TI  - Complications from recruitment maneuvers in patients with acute lung injury:
      secondary analysis from the lung open ventilation study.
AB  - BACKGROUND: There are limited data on the safety and efficacy of recruitment
      maneuvers (RMs) in acute lung injury (ALI) patients. OBJECTIVE: To evaluate the
      frequency, timing, and risk factors for complications from RMs in adult ALI
      patients. METHODS: Secondary analysis of data from  a randomized controlled trial
      of a lung open ventilation strategy that included sustained inflation RMs.
      RESULTS: Respiratory (eg, desaturation) and cardiovascular (eg, hypotension)
      complications from recruitment maneuvers were common (22% of all patients
      receiving RMs), and the majority occurred  within 7 days of enrollment. New air
      leak through an existing chest tube was uncommon (< 5%). As compared to patients
      receiving 1 or fewer RMs, the number of RMs received was associated with
      increased risk in both younger (age <= 56 y) and older patients (age > 56 y): 2
      RMs odds ratio  [OR] 6.92 (95% CI 1.70-28.2), >= 3 RMs OR 15.4 (95% CI 4.77
      49.6), and 2 RMs OR 5.43 (95% CI 1.76-16.8), >= 3 RMs OR 4.93 (95% CI 1.78-13.7),
      respectively. Patients with extrapulmonary ALI had decreased odds of developing
      complications (OR 0.42, 95% CI 0.22-0.80). CONCLUSIONS: Complications in adult
      ALI patients receiving RMs were common, but serious complications (eg, new air
      leak through an existing chest tube) were infrequent. There is a significant
      association between the number of RMs received and complications, even after
      controlling for illness  severity and duration. Given their uncertain benefit in
      ALI patients, and the potential for complications with repeated application, the
      routine use of sustained inflation RMs is not justified.

PMID- 22613635
TI  - The role of GABAergic system on the inhibitory effect of ghrelin on food intake
      in neonatal chicks.
AB  - Ghrelin is a gut-brain peptide that has a stimulatory effect on food intake in
      mammals. In contrast, this peptide decreases food intake in neonatal chicks when
      injected intracerebroventricularly (ICV). In mammals, neuropeptide Y (NPY)
      mediates the orexigenic effect of ghrelin whereas in chicks it appears that
      corticotrophin releasing factor (CRF) is partially involved in the inhibitory
      effect of ghrelin on food intake. Gamma aminobutyric acid (GABA) has a
      stimulatory effect on food intake in mammals and birds. In this study we
      investigated whether the anorectic effect of ghrelin is mediated by the GABAergic
      system. In Experiment 1, 3h-fasted chicks were given an ICV injection of chicken
      ghrelin and picrotoxin, a GABA(A) receptors antagonist. Picrotoxin decreased food
      intake compared to the control chicks indicating a stimulatory effect of GABA(A)
      receptors on food intake. However, picrotoxin did not alter the inhibitory effect
      of ghrelin on food intake. In Experiment 2, THIP hydrochloride, a GABA(A)
      receptor agonist, was used in place of picrotoxin. THIP hydrochloride appeared to
      partially attenuate the decrease in food intake induced by ghrelin at 30 min
      postinjection. In Experiment 3, the effect of ICV injection of chicken ghrelin on
      gene expression of glutamate decarboxylase (GAD)(1) and GAD(2), GABA synthesis
      enzymes in the brain stem including hypothalamus, was investigated. The ICV
      injection of chicken ghrelin significantly reduced GAD(2) gene expression. These
      findings suggest that ghrelin may decrease food intake in neonatal chicks by
      reducing GABA synthesis and thereby GABA release within brain feeding centers.

PMID- 22613636
TI  - Percutaneous transluminal renal angioplasty with stent is effective for blood
      pressure control and renal function improvement in atherosclerotic renal artery
      stenosis patients.
AB  - BACKGROUND: Percutaneous transluminal renal angioplasty with stent is an
      effective procedure for atherosclerotic renal artery stenosis. However, the
      decision to perform this procedure has recently raised considerable debate. The
      aim of this study was to assess the effects of percutaneous transluminal renal
      angioplasty with stent in atherosclerotic renal artery stenosis patients,
      especially as it relates to blood pressure control and renal function
      improvement. METHODS: A retrospective analysis was made of the clinical data from
      125 atherosclerotic renal artery stenosis patients who underwent percutaneous
      transluminal renal angioplasty from July 2004 to June 2008 in the Department of
      Vascular Surgery of Beijing Chaoyang Hospital. We compared blood pressure, number
      of oral antihypertensive medications, and renal function changes pre and post
      procedure at 24 months follow-up. RESULTS: A total of 125 atherosclerotic renal
      artery stenosis patients underwent percutaneous transluminal renal angioplasty
      and 143 stents were placed. At 24 months follow-up, both systolic and diastolic
      blood pressure and the number of oral antihypertensive medications were
      significantly reduced (P < 0.05). Overall, the estimated glomerular filtration
      rate did not change significantly (P > 0.05); however, a significant increase in
      estimated glomerular filtration rate was observed in the subgroup of patients
      with a lower baseline estimated glomerular filtration rate and in the subgroup of
      patients with bilateral renal artery stenosis (P < 0.05). CONCLUSION:
      Percutaneous transluminal renal angioplasty is a safe procedure for
      atherosclerotic renal artery stenosis patients, providing a significant
      improvement in blood pressure control and reduction in the number of oral
      antihypertensive medications.

PMID- 22613637
TI  - Angiogenesis related gene expression profiles of EA.hy926 cells induced by
      irbesartan: a possible novel therapeutic approach.
AB  - BACKGROUND: Angiogenesis occurs commonly in various physiological and
      pathological processes. Improving blood supply through promoting angiogenesis is
      a novel approach for treating ischemic diseases. Angiotensin II type 1 receptor
      blockers (ARBs) dominate the management of hypertension, but evidence of their
      role in angiogenesis is contradictory. Here we explored the angiogenic effects of
      ARBs through characterizing gene expression of the human umbilical vein
      endothelial cell line EA.hy926 exposed to irbesartan. METHODS: The human
      umbilical vein endothelial cell line EA.hy926 was grown for 72 hours after
      treatment with different concentrations of irbesartan. The cell proliferative
      capacity was assessed by CCK8 assay at 24, 48 and 72 hours. Gene expression
      levels in EA.hy926 cells responding to irbesartan were measured under optimal
      proliferation conditions by microarray analysis using Affymetrix U133 plus 2.0.
      The differential expression of genes involved in angiogenesis was identified
      through cluster analysis of the resulting microarray data. Quantitative RT-PCR
      and Western blotting analyses were used to validate differential gene expression
      related to the angiogenesis process. RESULTS: In the 10(-4), 10(-5), 10(-6) mol/L
      treatment groups, cell proliferation studies revealed significantly increased
      proliferation in EA.hy926 cells after 24 hours of irbesartan treatment. However,
      after 48 and 72 hours of treatment with different concentrations of irbesartan,
      there was no significant difference in cell proliferation observed in any
      treatment group. We selected the group stimulated with irbersartan at a
      concentration of 10(-6) mol/L for microarray experiments. Statistical analysis of
      the microarray data resulted in the identification of 56 gene transcripts whose
      expression patterns were significantly correlated, negatively or positively, with
      irbesartan treatment. Cluster analysis showed that these genes were involved in
      angiogenesis, extracellular stimulus, binding reactions and skeletal system
      morphogenesis. Of these 56 genes we identified seven genes (VEGF, KDR, PTGS2,
      PLXND1, ROBO4, LMO2, and COL5A1) involved in the angiogenesis process. qRT-PCR
      analysis of these genes confirmed the microarray results. Protein expression of
      three VEGF pathway genes (VEGF, KDR, and PTGS2) was further confirmed by Western
      blotting. CONCLUSIONS: Our study showed that irbesartan may induce angiogenic
      effects in vascular endothelial cells. It suggested that the mechanism of
      angiogenic effects of ARBs might be attributed to the signaling cascade from
      angiotensin receptors in the VEGF pathway. It also provided evidence indicating
      that ARBs could be used as a novel therapeutic approach to treat chronic ischemic
      heart disease as well as anti-hypertensive agents.

PMID- 22613638
TI  - Combined laparoscopic and thoracoscopic Ivor Lewis esophagectomy for esophageal
      cancer: initial experience from China.
AB  - BACKGROUND: Minimally invasive Ivor Lewis esophagectomy was usually performed
      with either hand-sewn or circular stapler anastomosis through a small thoracotomy
      or using a side-to-side stapler anastomotic technique. This study aimed to
      present our initial results of Ivor Lewis esophagectomy using a circular-stapled
      anastomosis with transoral anvil technique. METHODS: Six patients with esophageal
      cancer underwent minimally invasive Ivor Lewis esophagectomy with an
      intrathoracic circular-stapled end-to-end anastomosis. The abdominal portion was
      operated on laparoscopically, and the thoracic portion was done using
      thoracoscopic techniques. A 25 mm anvil connected to a 90 cm long delivery tube
      was introduced transorally to the esophageal stump in a tilted position, the
      anvil head was then connected to circular stapler. The anastomosis was completed
      under direct thoracoscopic view. RESULTS: A total of six patients in this report
      successfully underwent total laparoscopic and thoracoscopic Ivor Lewis
      esophagectomy with a circular-stapled anastomosis using a transoral anvil. They
      were five male and one female patients, and had a mean age of 55 years (range, 38
      69 years). The thoracic and abdominal operations were successfully performed
      without any intraoperative complications or conversion to laparotomy or
      thoracotomy. The passage of the anvil head was technically easy and successful in
      all six cases. The mean overall operative time was (260 +/- 42) minutes (range,
      220-300 minutes), and the mean estimated blood loss was (520 +/- 160) ml (range,
      130-800 ml). Patients resumed a liquid oral diet on postoperative day seven. The
      median length of hospital stay was 17 days (range, 9-25 days). The postoperative
      pathological diagnosis was esophageal squamous cell carcinoma in five patients
      and esophageal small cell carcinoma in one patient. Tumors were staged as
      T(2)N(0)M(0) in three cases, T(2)N(1)M(0) in one case, and T(3)N(0)M(0) in two
      cases. During the mean follow-up of 2.5 months (range, 2-4 months), there were no
      intraoperative technical failure of the anastomosis or major postoperative
      complications such as leak or stricture. CONCLUSIONS: The initial results of this
      small series suggest that minimally invasive Ivor Lewis esophagectomy for
      malignant esophageal tumor is technically feasible. However, further multi-center
      prospective studies and thorough evaluation are needed to evaluate the long-term
      results.

PMID- 22613639
TI  - Angiotensin-converting enzyme 2 activation protects against pulmonary arterial
      hypertension through improving early endothelial function and mediating cytokines
      levels.
AB  - BACKGROUND: Increasing evidences indicate that an activated renin-angiotensin
      system (RAS) causes an imbalance between the vasoconstrictive and vasodilator
      mechanisms involving the pulmonary circulation leading to the development of
      pulmonary arterial hypertension (PAH). Angiotensin-converting enzyme 2 (ACE2), a
      primary component of the vasoprotective axis in RAS, is recently identified that
      it has regulatory actions in lung pathophysiology, but the mechanism in these
      processes is uncertain yet. METHODS: Severe PAH was induced by monocrotaline
      injection one week following pneumonectomy in rats. The activation of ACE2 by
      continuous injection of resorcinolnaphthalein was studied by real time-polymerase
      chain reaction (RT-PCR), Western blotting and fluorogenic peptide assay.
      Endothelial functions were evaluated by the response to acetylcholine and
      cytokines were measured by RT-PCR seven days after monocrotaline injection. The
      PAH-related hemodynamics and pathological changes were examined at day 21 when
      severe PAH was completely established. RESULTS: Resorcinolnaphthalein caused
      significant activation of ACE2 in both normal and diseased rats in 7 days after
      treatment. The pulmonary arterial pressure (PAP) started to increase at least 7
      days after monocrotaline injection, and the rats developed severe PAH in 21 days
      with high PAP, right ventricular hypertrophy and neointimal formation. Treatment
      with resorcinolnaphthalein prevented these features. Resorcinolnaphthalein caused
      an improved endothelia-dependent vasorelaxation and decrease in proinflammatory
      cytokines (tumor necrosis factor (TNF)-alpha, monocyte chemoattractant protein-1
      (MCP-1), interleukin (IL)-6) and increase in anti-inflammatory cytokine IL-10 in
      the early stage of the pathogenesis. CONCLUSIONS: These results demonstrated that
      activation of ACE2 by continuous injection of resorcinolnaphthalein prevented the
      development of PAH through improving early endothelial dysfunction and mediating
      the level of proinflammatory and anti-inflammatory cytokines.

PMID- 22613640
TI  - Evaluation of entropy for monitoring the depth of anesthesia compared with
      bispectral index: a multicenter clinical trial.
AB  - BACKGROUND: As a new electroencephalogram (EEG) signal processing technique for
      monitoring the depth of anesthesia, entropy consists of two indices: reaction
      entropy (RE) and state entropy (SE). Our study compared entropy with classical
      bispectral index (BIS) in reduction of myoelectrical interference and noxious
      stimuli with EEG signals. METHODS: Two hundred and eighty patients (ASA I-II, 18
      60 years old) undergoing scheduled surgeries from seven medical centers were
      enrolled. Anesthesia induction was managed with propofol via the target
      controlled infusion (TCI) system. The results of BIS, RE, SE, mean arterial
      pressure (MAP) and heart rate (HR) were recorded before anesthesia induction, at
      the moment of unconsciousness, before and 2 minutes after administration of
      muscle relaxant, and before and one and three minutes after the tracheal
      intubation. RESULTS: The values of half maximum effective concentrations (EC50),
      5% effective concentrations (EC05) and 95% effective concentrations (EC95) of
      propofol effect-site concentration at the onset of unconsciousness were 1.2 (1.1
      1.3 ug/ml), 2.5 (2.4-2.5 ug/ml) and 3.7 (3.7-3.8 ug/ml), while those of the
      predicted plasma propofol concentration were 2.8 (2.7-2.9 ug/ml), 3.9 (3.8-3.9
      ug/ml) and 4.9 (4.8-5.0 ug/ml), respectively. The values of BIS, SE and RE were
      62, 59 and 63 when 50% of patients lost consciousness, and 79, 80, 85 and 42, 37,
      44, respectively, when 5% and 95% of patients were unconscious. The values of
      BIS, RE and SE dropped two minutes after the injection of muscle relaxant, but
      there were no significant differences between RE and SE. MAP and HR increased
      visibly, which indicated a reaction to tracheal intubation; the values of BIS, RE
      and SE, however, did not display any significant changes. CONCLUSIONS: This large
      sample multicentric study confirmed the values of RE and SE as approximating BIS
      value, at the onset of unconsciousness during propofol TCI anesthesia. After
      elimination of myoelectrical activation, all values of RE, SE and BIS decreased
      significantly and the three indices were less sensitive to noxious stimuli than
      cardiovascular responses.

PMID- 22613643
TI  - Impact of emergency percutaneous coronary intervention on outcomes of ST-segment
      elevation myocardial infarction patients complicated by out-of-hospital cardiac
      arrest.
AB  - BACKGROUND: Cardiac arrest is one of the most serious complications of acute
      myocardial infarction (AMI), especially in the out-of-hospital patients. There is
      no general consensus as to whether percutaneous coronary intervention (PCI) is
      effective in treating ST-segment elevation myocardial infarction (STEMI) patients
      complicated by out-of-hospital cardiac arrest (OHCA). In our study, we evaluated
      the efficacy of PCI in treating STEMI patients complicated by OHCA through
      observing their clinical conditions in hospital; including total mortality,
      adverse cardiac events, stroke, acute renal failure, and gastrointestinal
      bleeding events. METHODS: A total of 1827 STEMI patients were enrolled in this
      study, where 81 were STEMI with OHCA. Between the patients with and without OHCA,
      and the OHCA patients with and without PCI, we compared the clinical
      characteristics during hospitalization, including total mortality and incidences
      of adverse cardiac events, and stroke. RESULTS: Compared to the patients without
      OHCA, the OHCA patients had significantly lower systolic blood pressure (P <
      0.05) and a faster heart rate (P < 0.05), and a higher percentage of Killip class
      IV or Glasgow coma scale (GCS) <= 7 on admission (P < 0.001). And the in-hospital
      mortality was higher in the OHCA patients (55.6% vs. 2.4%, P < 0.001). Comparing
      the OHCA patients without PCI to the patients with PCI, there was no obvious
      difference of heart rate, blood pressure or the percentage of Killip class IV and
      GCS <= 7 on admission, but the incidences of cardiogenic shock, stroke were
      significantly lower in the with-PCI group during hospitalization (P < 0.001, P <
      0.05). And the in-hospital mortality of the OHCA patients receiving PCI was
      significantly lower (36.7% vs. 84.3%, P < 0.001). CONCLUSIONS: During
      hospitalization, the incidence of adverse events and mortality are higher in the
      STEMI with OHCA patients, comparing with the STEMI without OHCA. Emergency PCI
      reduces the incidence of adverse events and decreases mortality during
      hospitalization, which is effective for treating STEMI with OHCA patients.

PMID- 22613641
TI  - Who are more at risk for acute mountain sickness: a prospective study in Qinghai
      Tibet railroad construction workers on Mt. Tanggula.
AB  - BACKGROUND: It is important to determine the incidence of acute mountain sickness
      (AMS) among workers at altitudes between 3500 m and 5000 m on Mt. Tanggula during
      the construction of the Qinghai-Tibet railroad. This study explored the risk
      factors predisposing workers to developing AMS and attempted to develop more
      effective ways of preventing and treating AMS. METHODS: A total of 11,182 workers
      were surveyed by completing twice daily a Lake Louise questionnaire, and a score
      >= 3 indicated AMS. The contributing risk factors were assessed for at least 2
      months for the duration of the study in the years from 2001 to 2003. A risk model
      was developed by multiple Logistic regression. Standard statistical methods were
      used to analyze data. RESULTS: AMS occurred in 56% of workers working at high
      altitudes on Mt. Tanggula. The incidence of AMS increased with increasing
      altitude. Rapid ascent to an altitude above 3500 m, sea-level or lowland
      newcomers, young people under 25 years of age, heavy physical exertion, obese
      person, and arterial oxygen saturation (SaO2) below 80% were independent AMS risk
      factors. No significant association was found between AMS and sex or taking
      Rhodiola. Medical education contributed to an early diagnosis of AMS.
      CONCLUSIONS: This study used the Lake Louise scoring system suggesting that it is
      a well-validated standard for field evaluation of AMS and for making an early
      diagnosis. These studies have described many variables regarding risk factors for
      the development of AMS. Risk factors which can be modified should be attended to,
      and the physicians should carry out check-ups and tests to identify subjects who
      are more at risk. Prevention consists in continuous gradual ascent, medical
      education, and prompt descent to avoid progression in patients with serious AMS.
      It is most important to effectively control the risk factors of AMS.

PMID- 22613642
TI  - Genetic diagnosis of Liddle's syndrome by mutation analysis of SCNN1B and SCNN1G
      in a Chinese family.
AB  - BACKGROUND: Liddle's syndrome is a rare autosomal-dominant monogenic form of salt
      sensitive hypertension. This study aimed to screen the gene mutation in beta and
      gamma subunits of the epithelial sodium channel (ENaC) of a Chinese family with
      Liddle's syndrome, an autosomal dominant form of hypertension. METHODS: DNA
      samples from the proband with early-onset, treatment-resistant hypertension and
      suppressed plasma renin activity were initially screened for mutations in the C
      terminal exons of the ENaC beta or gamma subunit genes, using amplification by
      polymerase chain reaction and direct DNA sequencing. We also screened the C
      terminus of SCNN1B and SCNN1G in family members, and screened for the mutation in
      150 controls. RESULTS: Genetic analysis of the beta ENaC gene revealed a missense
      mutation of CCC to TCC at codon 616 in the proband, her mother and her
      grandmother. One hundred and fifty randomly selected controls had not the
      mutation, indicating that this is not a common genetic polymorphism. There was no
      mutation of the gamma ENaC gene in any of the individuals examined. CONCLUSIONS:
      Through direct DNA sequencing analysis, we established the diagnosis of Liddle's
      syndrome for the proband and her families, and provided tailored therapies to
      this abnormality. These results provide further evidence that Pro616Ser is a
      critical amino acid that has a key role in the inhibition of sodium channel
      activity.

PMID- 22613644
TI  - Cytokeratin 19 fragment antigen 21-1 as an independent predictor for definitive
      chemoradiotherapy sensitivity in esophageal squamous cell carcinoma.
AB  - BACKGROUND: Patients with esophageal squamous cell carcinoma (ESCC) undergoing
      definitive chemoradiotherapy (CRT) seem to have a disparity in therapeutic
      response. The identification of CRT sensitivity-related clinicopathological
      factors would be helpful for selecting patients most likely to benefit from CRT.
      Cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) and carcinoembryonic antigen
      (CEA) have been reported as useful tumor markers for esophageal cancer. The aim
      of this study was to examine the predictive value of CYFRA21-1 in comparison with
      CEA and other clinicopathological factors in patients with ESCC treated with
      definitive CRT. METHODS: Pretreatment serum CYFRA21-1 and CEA levels were
      measured by immunoradiometric assays. The relationships between pretreatment
      clinicopathological factors and the efficacy of CRT were analyzed. Overall
      survival (OS) was estimated by univariate and multivariate analysis. RESULTS: The
      results from a univariate analysis indicated that the efficacy of CRT was
      significantly associated with the serum levels of CYFRA21-1 and CEA before
      treatment (P = 0.001 and P = 0.023, respectively). It also indicated that the
      efficacy of CRT was significantly associated with the pretreatment tumor location
      (P = 0.041). By Logistic regression analysis, the independent predictive factor
      associated with efficacy of CRT was CYFRA21-1 (P = 0.002). The OS of the patients
      with high CYFRA 21-1 levels was worse than that of those with low CYFRA21-1
      levels (P = 0.001). In multivariate analysis, a low level of CYFRA21-1 was the
      most significant independent predictor of good OS (P = 0.007). CONCLUSIONS: CEA
      and tumor location may be useful in predicting the sensitivity of ESCC to CRT.
      CYFRA21-1 may be an independent predictor for definitive CRT sensitivity in ESCC.

PMID- 22613645
TI  - Association of nicotinamide adenine dinucleotide phosphate oxidase p22phox gene
      549C>T polymorphism with coronary artery disease.
AB  - BACKGROUND: The p22phox is a critical component of the superoxide-generating
      vascular nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Several
      polymorphisms in p22phox gene are studied for their association with
      cardiovascular diseases. However, no publication is available to assess the
      relation of 549C > T polymorphism in p22phox gene to coronary artery disease
      (CAD) risk. This study was to investigate the effect of the p22phox gene 549C > T
      polymorphism on CAD risk. METHODS: Hospital-based case-control study was
      conducted with 297 CAD patients and 343 healthy persons as the control group.
      Polymerase chain reaction and pyrosequencing using PSQ 96 MA Pyrosequencer
      (Biotage AB) were used to detect the polymorphisms. Multiple Logistic regression
      model was used to adjust the potential confounders and to estimate odds ratio
      (OR) with 95% confidence intervals (CIs). RESULTS: The observed genotype
      frequencies of this polymorphism obeyed the Hardy-Weinberg equilibrium in both
      cases (P = 0.439) and controls (P = 0.668). The frequency of mutant genotypes (TT
      + CT) in cases (41.08%) was higher than that in controls (36.73%) with an OR =
      1.20 (95%CI = 0.87-1.65). After the adjustment of the potential confounders,
      there was a significant association of the mutant genotypes with increased risk
      of CAD (OR = 1.57, 95%CI = 1.01-2.46, P = 0.047). CONCLUSIONS: The mutant
      genotypes of the p22phox gene 549C > T polymorphism had a significant effect on
      the increased risk of CAD in this studied population.

PMID- 22613646
TI  - External fixation in early treatment of unstable pelvic fractures.
AB  - BACKGROUND: Patients with pelvic fractures are often treated in hospitals without
      the capacity to implement an open reduction internal fixation (ORIF). This often
      leads to pelvic malunion in patients with unstable pelvic fracture, shock or even
      death due to uncontrollable pelvic hemorrhage and unstable hemodynamics. This
      study explored the role of early external fixation (within 7 days) for patients
      with unstable pelvic fractures. METHODS: A retrospective analysis was conducted
      on 32 patients with unstable pelvic fractures treated with early external
      fixation from January 2005 to January 2010 (Tile type B: 18 cases; C: 14 cases).
      The study comprised 28 males and 4 females, with a mean age of (32 +/- 8) years
      (range, 21-56 years). Of these patients, 22 were treated with emergency pelvic
      external fixation and 10 were treated with external fixation within 1-7 days.
      Fifteen cases suffered traumatic hemorrhagic shock. A statistical analysis was
      conducted to compare fluid infusion and blood transfusion volumes within the
      first 24 hours of these shock patients with another cohort of patients treated
      without early external fixation from January 1993 to January 1998. RESULTS: The
      average follow-up was (34.7 +/- 14.6) months (range, 6-66 months). Six to eight
      weeks after external fixation, patients could walk with crutches; by 12 weeks,
      external fixation was removed and all fractures had healed. Seven patients
      presented with sequelae, including 3 patients with long-term lumbosacral pain, 3
      patients with erectile dysfunction and 1 patient with Morel-Lavallee lesion and
      other complications. The 15 shock patients in this study (2005-2010 group)
      required significantly lower volumes of fluid infusion and blood transfusion
      (P(fluid) = 0.000; P(transfusion) = 0.000) as compared to the 1993-1998 cohort.
      CONCLUSIONS: The early application of external fixation in unstable pelvic
      fracture patients positively affects hemodynamic stability, with outstanding
      efficacy as a final fixation option for unstable pelvic fractures.

PMID- 22613647
TI  - Video-urodynamics study on female patients with bladder neck obstruction.
AB  - BACKGROUND: Pressure-flow study combined with cystourethroscopy were used as the
      major method to define female bladder neck obstruction in China. However, the
      definition of urodynamics for female bladder outlet obstruction (BOO) is not
      clear so far. Video-urodynamic study (VUDS) would provide more information to
      define the female BOO, but it is not used commonly due to the limitation of video
      urodynamic equipment in China. We attempted to find a better way for diagnosis of
      female BOO by performing VUDS. METHODS: VUDS and cystourethroscopy were performed
      in 38 women with signs and symptoms of difficult voiding from March 2008 to April
      2010 in Beijing Chao-Yang Hospital. Bladder neck obstruction was defined by
      radiological evidence of narrowing bladder neck, voiding pressure greater than 20
      cmH2O and maximum flow rate (Q(max)) less than 12 ml/s. Transurethral incision of
      bladder neck was then performed on those patients. Follow-up examination (Q(max)
      and residual urine) was recorded 3 months after operation. RESULTS: The mean time
      from its onset to diagnosis was (18.1 +/- 9.1) months in 38 patients. Average
      patient age was 36.1 years (range from 19 to 79 years). The mean Q(max) was (10.6
      +/- 4.7) ml/s and residual urine was (81.5 +/- 42.4) ml. Three out of 38 patients
      had obvious distal urethral stricture, eight of them suffered from definitely
      bladder neck contracture and the remaining 27 patients did not show obvious
      abnormalities measured by cystourethroscopy examination. For the 35 patients
      without urethral stricture, the most frequent findings of VUDS were high-voiding
      pressure plus low-flow rate and narrow bladder neck during voiding on
      simultaneous fluoroscopy examination. With video-urodynamics definition, 32
      patients were diagnosed as bladder neck obstruction with mean Q(max) of (10.8 +/-
      3.7) ml/s, residual urine of (76.9 +/- 32.7) ml and detrusor pressure at maximum
      flow (P(det Q(max))) of (50.7 +/- 19.1) cmH2O. Other three patients were suffered
      from detrusor hypocontractility. All 32 patients including eight with definitely
      bladder neck contracture and 24 with primary bladder neck obstruction received
      transurethral bladder neck incision. The symptom of difficult voiding was
      relieved. The postoperative follow-up showed that Q(max) was (21.7 +/- 7.6) ml/s
      (P < 0.01) and the residual urine was (23.2 +/- 17.6) ml (P < 0.01). CONCLUSIONS:
      The real cause of the obstruction for female patient with difficult voiding might
      be various. A full VUDS would give us valuable information for correct diagnosis
      in female patients with bladder neck obstruction.

PMID- 22613648
TI  - Comparison of combined phacotrabeculectomy with trabeculectomy only in the
      treatment of primary angle-closure glaucoma.
AB  - BACKGROUND: Trabeculectomy has become a mainstream treatment in intraocular
      pressure (IOP) reduction for primary angle-closure glaucoma (PACG); combined
      trabeculectomy and cataract surgery was reported to reduce IOP and simultaneously
      improve vision for patients with PACG and coexisting cataract. This study was
      specialized to compare the efficacy and safety of combined phacotrabeculectomy
      with that of trabeculectomy only in the treatment of PACG with coexisting
      cataract. METHODS: This is a comparative case series study. Thirty-one patients
      (31 eyes) with PACG and coexisting cataract were enrolled. Of these, 17 underwent
      phacotrabeculectomy and 14 underwent trabeculectomy alone. IOP, filtering blebs,
      and complications were compared at the final follow-up. Complete success was
      defined as a final IOP less than 21 mmHg without IOP-lowering medication.
      RESULTS: After 10 months of postoperative follow-up, the phacotrabeculectomy and
      trabeculectomy groups showed no significant differences regarding IOP reduction
      ((20.59 +/- 7.94) vs. (24.85 +/- 14.39) mmHg, P = 0.614), complete success rate
      (88% vs. 71%, P = 0.370), formation rate of functioning blebs (65% (11/17) vs.
      93% (13/14), P = 0.094), and complications (41% (7/17) vs. 57% (8/14), P =
      0.380). IOP-lowering medication was not required for most of the patients in both
      groups. Additional surgery interventions, including anterior chamber reformation
      and phacoemulsification, were needed in the trabeculectomy group, whereas no
      surgery was needed postoperatively in the phacotrabeculectomy group. CONCLUSION:
      Phacotrabeculectomy and trabeculectomy treatments exhibit similar IOP reduction,
      successful rates, and complications when it comes to treating PACG patients with
      coexisting cataract, although additional surgery intervention may be needed for a
      few cases with cataract and complications after trabeculectomy.

PMID- 22613650
TI  - Factors as predictors for thoracic and thoracolumbar/lumbar structural curves in
      adolescent idiopathic scoliosis.
AB  - BACKGROUND: Recent studies have demonstrated that the Lenke system is relatively
      efficient and consistent in classifying scoliosis curves. Basically, fusion
      should include the main curve and the structural minor curve. The criteria for
      defining the structural minor curve were established to help guide these decision
      making process. The present study was designed to investigate predictors of the
      structural curve, and see whether it was possible to prevent the formation of the
      structural curve by interfering with influencing factors to decrease the fusion
      level. METHODS: Age, gender, Cobb angle, Perdriolle rotation, Risser sign and the
      number of vertebrae included in the curve, brace treatment, and curve location
      were recorded in 145 idiopathic scoliosis patients from July 2001 to January
      2007. The patients were divided into two groups: structural and non-structural
      groups. Demographics and baseline characteristics were compared between the two
      groups as an initial screen. Logistic regression was used to analyze factors
      affecting the minor curve to become the structural curve. RESULTS: Compared with
      the non-structural group, the structural group had a higher Cobb angle ((51.34 +/
      13.61) degrees  vs. (34.20 +/- 7.21) degrees , P < 0.001), bending angle ((33.94
      +/- 9.92) degrees  vs. (8.46 +/- 5.56) degrees , P < 0.001) and curve rotation
      ((23.25 +/- 12.86) degrees  vs. (14.21 +/- 8.55) degrees , P < 0.001), and lower
      flexibility ((33.48 +/- 12.53)% vs. (75.50 +/- 15.52)%, P < 0.001). There was no
      significant difference in other parameters between the two groups. The results of
      the Logistic regression analysis showed that the Cobb angle (OR: 9.921, P <
      0.001) and curve location (OR: 4.119, P = 0.016) were significant predictors of
      structural curve in adolescent idiopathic scoliosis. Every 10 degrees  change of
      Cobb angle increased the possibility of turning the minor curve into the
      structural curve by 10-fold. And thoracic curve showed, on the average, the
      possibility of becoming the structural curve about 4-fold more often than did the
      thoracolumbar/lumbar curve. CONCLUSIONS: Curve severity and curve location affect
      the minor curve's structural features in adolescent idiopathic scoliosis.

PMID- 22613649
TI  - Effect of oxymatrine on specific cytotoxic T lymphocyte surface programmed death
      receptor-1 expression in patients with chronic hepatitis B.
AB  - BACKGROUND: Oxymatrine has certain antiviral effects in the treatment of chronic
      hepatitis B (CHB), but its exact mechanism is unclear. The objective of the
      present study was to explore oxymatrine's antiviral mechanism by studying its
      effect on the hepatitis B virus (HBV) specific cytotoxic T lymphocyte (CTL)
      surface programmed death receptor-1 (PD-1) expression in CHB patients. METHODS:
      Sixty-five CHB patients who had HBV DNA(3)10(4) copies/ml, positive HBeAg,
      positive human leukocyte antigen (HLA)-A2, alanine aminotransferase (ALT) > 2 x
      upper limit of normal value (ULN) were randomly divided into two groups:
      treatment group (n = 33), treated with an intravenous infusion of 600 mg
      oxymatrine in glucose solution once a day for a month, then with a 200 mg
      oxymatrine oral capsule three times a day, and a 200 mg silibin meglumine tablet
      three times a day; control group (n = 32) patients were treated only with silibin
      meglumine tablet, method and dosage were the same as those of treatment group.
      Three months later, peripheral blood HBV-specific CTL surface PD-1 expression,
      HBV-specific CTL level, HBV DNA, HBeAg, and results of liver function tests were
      analyzed and compared. RESULTS: Three months post-treatment, in the treatment
      group, peripheral blood HBV-specific CTL surface PD-1 expression ((19.42 +/-
      15.94)%) decreased significantly compared to the pretreatment level ((31.30 +/-
      24.06)%; P < 0.05), and decreased significantly compared to that of control group
      three months after treatment ((29.45 +/- 21.62)%; P < 0.05). HBV-specific CTL
      level ((0.42 +/- 0.07)%) significantly increased compared with the pretreatment
      ((0.29 +/- 0.15)%; P < 0.01), and the control group posttreatment level was (0.31
      +/- 0.15)% (P < 0.05). HBV DNA level in 11 cases became negative (HBV DNA < 500
      copies/ml, 33.33%), which was higher than that of the control group after
      treatment (two cases, 6.25%; chi(2) = 7.45, P < 0.01), HBeAg of nine cases turned
      negative (27.27%), which was higher than that of the control group after
      treatment (one case, 3.13%; chi(2) = 7.27, P < 0.01). CONCLUSION: Oxymatrine
      could downregulate peripheral blood HBV-specific CTL surface PD-1 expression in
      CHB patients, increase HBV-specific CTL level, which may be one of the possible
      mechanisms by which oxymatrine clears or inhibits HBV in CHB patients.

PMID- 22613651
TI  - Surgical treatment of cervicothoracic junction spinal tuberculosis via combined
      anterior and posterior approaches in children.
AB  - BACKGROUND: Cervicothoracic junction spinal tuberculosis (CJST) in children is
      uncommon, especially when accompanied by a huge abscess. However, its
      consequences can be severe. Because of the special anatomic location of the
      cervicothoracic junction, surgical treatment is difficult and rarely reported.
      The aim of this clinical study was to assess the effectiveness of combined
      anterior and posterior approaches for focal debridement, decompression,
      allografting and anterior instrumentation in the treatment of CJST in children.
      METHODS: Ten pediatric CJST patients underwent focal debridement and cord
      decompression through combined anterior and posterior approaches. Then an
      appropriate allograft and titanium plate were applied to reconstruct the spine.
      The patients were asked to wear head-neck-chest braces for six months and
      received regular anti-tubercular drugs therapy for 12 months. RESULTS: The
      patients were followed-up for an average of 26 months (range, 15-32 months).
      There was no recurrent tuberculous infection. The bone grafts incorporated well
      and the instrumentation was stable. Cervical and thoracic kyphosis was
      successfully corrected from 40 degrees  (range, 30-52 degrees ) before the
      operation to 18 degrees  (range, 12-26 degrees ) post-operation. Neurological
      function was improved in all patients. CONCLUSIONS: Combined anterior and
      posterior approaches for focal debridement, decompression, bone allografting and
      anterior instrumentation provided an effective means of treatment in children of
      CJST with a huge abscess in the posterior part of the vertebral body.

PMID- 22613652
TI  - Impact of a nationwide training program for neonatal resuscitation in China.
AB  - BACKGROUND: Seventeen million births occur in China each year. Neonatal mortality
      is the leading cause of under 5-year-old child deaths, and intrapartum-related
      injury accounts for much of mental retardation in young children. The Chinese
      Ministry of Health sought to improve infant and child survival through a
      nationwide initiative to have at least one person trained in neonatal
      resuscitation at every birth. The aim of the current study was to evaluate the
      impact of China Neonatal Resuscitation Program (NRP) on policy and infrastructure
      changes and its effectiveness in decreasing the incidence of mortality among
      newborn infants. METHODS: The Chinese NRP incorporated policy change,
      professional education, and creation of a sustainable health system
      infrastructure for resuscitation. Multidisciplinary teams from all 31 provinces
      and municipal states disseminated NRP in a train-the-trainer cascade. The
      intervention targeted 20 provinces with high neonatal mortality and programs to
      reduce maternal mortality. Program evaluation data came from 322 representative
      hospitals in those provinces. RESULTS: Changes in policy permitted midwives to
      initiate resuscitation and required resuscitation training for licensure. From
      2004 through 2009 more than 110,659 professionals received NRP training in the 20
      target provinces, with 94% of delivery facilities and 99% of counties reached.
      Intrapartum-related deaths in the delivery room decreased from 7.5 to 3.4 per
      10,000 from 2003 to 2008, and the incidence of Apgar <= 7 at 1 minute decreased
      from 6.3% to 2.9%. CONCLUSIONS: The Chinese NRP achieved policy changes promoting
      resuscitation, trained large numbers of professionals, and contributed to
      reduction in delivery room mortality. Improved adherence to the resuscitation
      algorithm, extension of training to the township level, and coverage of births
      now occurring outside health facilities can further increase the number of lives
      saved.

PMID- 22613654
TI  - Association of T regulatory cells with natural course and response to treatment
      with interferon-alpha in patients with chronic hepatitis B infection.
AB  - BACKGROUND: Regulatory T cell populations, particularly CD4(+)CD25(+) T
      regulatory cells, have been implicated in the persistence of hepatitis B virus
      (HBV) infection. However, no clear relationship has been established between the
      frequency of CD4(+)CD25(+) T regulatory cells in the peripheral blood and either
      the disease phases in the natural history of chronic HBV infection or in the
      response to interferon-alpha therapy. METHODS: In the present study, three
      different common markers of CD4(+)CD25(+) T regulatory cells were used to
      determine the numbers of T regulatory cells in healthy controls and in patients
      with chronic HBV infection. RESULTS: No significant difference was found when
      samples were gated for CD25(hi) and CD25(+)FoxP3(+) T cells. A significant
      correlation was found between the number of CD4(+) Treg cells that gated with
      CD25(+)FoxP3(+) and CD25(+)CD127(low/-) in healthy controls and in patients with
      chronic hepatitis B (CHB) (r = 0.67, 0.59; P < 0.01). The percentages of Treg
      cells were (8.56 +/- 2.01)% in asymptomatic carriers (Asc), (8.74 +/- 3.04)% in
      inactive HBsAg carriers, (10.7 +/- 2.93)% in CHB and (7.42 +/- 1.28)% in healthy
      controls (F = 11.1, P < 0.001). The percentage of Treg cells in patients with CHB
      was higher than in asymptomatic HBV patients, inactive HBsAg carriers, or healthy
      controls (P < 0.01). The proportion of CD4(+)CD25(+)CD127(low/-) T cells in
      patients who responded to interferon-alpha was (11.9 +/- 3.3)%, (9.1 +/- 2.4)%
      and (9.0 +/- 2.9)% at baseline, week 12 and week 24 after treatment, respectively
      (Z = 2.42, P < 0.05; Z = 2.67, P < 0.01). CONCLUSIONS: These results suggest that
      the proportion of the CD4(+)CD25(+) regulatory T cells might be affected by the
      application of different markers in process to detect T regulatory cells. The
      frequency of Treg cells was increased in patients with CHB, which might be
      associated with the disease activity of these patients and contribute to
      prevention of extensive liver damage. A decline in Treg cells at week 12 of
      treatment might be associated with a better response to treatment with interferon
      alpha.

PMID- 22613653
TI  - Rosuvastatin attenuates mucus secretion in a murine model of chronic asthma by
      inhibiting the gamma-aminobutyric acid type A receptor.
AB  - BACKGROUND: Asthma is a chronic inflammatory disease characterized by reversible
      bronchial constriction, pulmonary inflammation and airway remodeling. Current
      standard therapies for asthma provide symptomatic control, but fail to target the
      underlying disease pathology. Furthermore, no therapeutic agent is effective in
      preventing airway remodeling. A substantial amount of evidence suggests that
      statins have anti-inflammatory properties and immunomodulatory activity. In this
      study, we investigated the effect of rosuvastatin on airway inflammation and its
      inhibitory mechanism in mucus hypersecretion in a murine model of chronic asthma.
      METHODS: BALB/c mice were sensitized and challenged by ovalbumin to induce
      asthma. The recruitment of inflammatory cells into bronchoalveolar lavage fluid
      (BALF) and the lung tissues were measured by Diff-Quik staining and hematoxylin
      and eosin (H&E) staining. ELISA was used for measuring the levels of IL-4, IL-5,
      IL-13 and TNF-alpha in BALF. Periodic acid-Schiff (PAS) staining was used for
      mucus secretion. Gamma-aminobutyric acid type A receptor (GABAAR) beta2
      expression was measured by means of immunohistochemistry, reverse transcription
      polymerase chain reaction (RT-PCR) and Western blotting. RESULTS: Rosuvastatin
      reduced the number of total inflammatory cells, lymphocytes, macrophages,
      neutrophils, and eosinophils recruited into BALF, the levels of IL-4, IL-5, IL-13
      and TNF-alpha in BALF, along with the histological mucus index (HMI) and GABAAR
      beta2 expression. Changes occurred in a dose-dependent manner. CONCLUSIONS: Based
      on its ability to reduce the inflammatory response and mucus hypersecretion by
      regulating GABAAR activity in a murine model of chronic asthma, rosuvastatin may
      be a useful therapeutic agent for treatment of asthma.

PMID- 22613655
TI  - Assessment of right ventricular function for patients with rheumatic mitral
      stenosis by 64-slice multi-detector row computed tomography: comparison with
      magnetic resonance imaging.
AB  - BACKGROUND: Right ventricular (RV) dysfunction ensues due to rheumatic mitral
      stenosis (RMS). The evaluation of RV function is clinically important for the
      diagnosis, treatment, and follow-up for patients with different degrees of RMS.
      The purpose of this study was to determine whether the 64-slice multi-detector
      row computed tomography (64-slice MDCT) can assess the RV function in RMS with
      high accuracy and reproducibility when compared to MR imaging (MRI). METHODS:
      Right ventricular end-diastolic and end-systolic volumes (RV-EDV and RV-ESV),
      stroke volume (RV-SV), ejection fraction (RV-EF), cardiac output (RV-CO), and
      wall mass (RV-Mass) were measured with dedicated cardiac analysis software on 64
      slice MDCT and compared with values measured with MRI in 43 consecutive patients
      with RMS. Agreement between MRI and 64-MDCT results were compared with Bland and
      Altman analysis and linear regression analysis. Repeated measurements were
      performed to determine intraobserver and interobserver variability. RESULTS: No
      significant differences were revealed in calculated RV function parameters
      between the two methods. RV-EDV, RV-ESV, RV-SV, RV-EF, RV-CO, and RV-Mass by 64
      slice MDCT were similar to those by MRI (P > 0.05). There were good correlations
      (r = 0.98, 0.97, 0.96, 0.96, 0.95 and 0.77, respectively) and close agreement
      (bias = -0.2 ml, -1.0 ml, 0.8 ml, 0.5%, 26.1 ml, and 0.5 g, respectively, P >
      0.05). The variability in 64-slice MDCT measurements was similar to that in MRI
      values. CONCLUSION: ECG-gated 64-slice MDCT could assess the RV function in RMS
      with high accuracy and reproducibility when compared to MRI.

PMID- 22613656
TI  - Transurethral seminal vesiculoscopy in the diagnosis and treatment of seminal
      vesicle stones.
AB  - BACKGROUND: Seminal vesicle stones are one of the main causes of persistent
      hemospermia. Treatment requires removal of the stone, generally through open
      vesiculectomy. The purpose of this study was to apply a transurethral seminal
      vesiculoscopy for diagnosis and treatment of the seminal vesicle stones with an
      ureteroscope. We assessed whether this transurethral endoscopic technique is
      feasible and effective in the diagnosis and treatment of the seminal vesicle
      stones with intractable hemospermia. METHODS: Totally 12 patients with
      intractable hemospermia underwent transurethral seminal vesiculoscopy through the
      distal seminal tracts using a 7.3-French rigid ureteroscope. Age of patients
      ranged from 25 to 57 years (mean age (43.7 +/- 10.5) years). The patients'
      symptoms ranged in duration from 4 to 180 months (mean duration (47.8 +/- 45.3)
      months). All patients underwent transrectal ultrasonography, pelvic computed
      tomography or magnetic resonance imaging before the operation. Positive imaging
      findings were observed in patients with seminal vesicle stones and dilated
      seminal vesicle size. A 7.3-French rigid ureteroscope entered the lumen of the
      verumontanum, and then the seminal vesicle under direct vision. Seminal vesicle
      stones were found unilaterally in 11 cases and bilaterally in one case. RESULTS:
      All 12 patients successfully underwent transurethral seminal vesiculoscopy. The
      seminal vesicle interior with single or multiple yellowish stones ranging from 1
      to 5 mm in diameter was clearly visible. All the stones were easily fragmented
      and endoscopically removed using a grasper. The operative time was 30 to 120
      minutes (mean (49 +/- 22) minutes). The mean follow-up period was (6.9 +/- 3.0)
      months (range 3-13 months). Symptoms of hemospermia disappeared after one month
      in 10 patients and after three months in two patients. Three patients with
      painful ejaculation could completely be relieved postoperation. There was also
      improvement in one patient with erectile dysfunction. There were no postoperative
      complications. CONCLUSIONS: Transurethral seminal vesiculoscopy is safe and
      effective in the diagnosis and treatment of seminal vesicle stones. This
      endoscopic technique can be performed with minimal complications.

PMID- 22613657
TI  - Review of clinical investigation on recurrence of gastric cancer following
      curative resection.
AB  - OBJECTIVE: To discuss the present status and progress of clinical research on
      recurrence of gastric cancer after surgery, including patterns, clinicopathologic
      factors, prognosis, detection, diagnosis, prevention, and treatment strategies.
      DATA SOURCES: The data used in this review were mainly from PubMed articles
      published in English from 2000 to August 2011. The search terms were "gastric
      cancer" and "recurrence". STUDY SELECTION: Articles were selected if they
      involved clinicopathologic factors, detection methods, and treatment strategies
      of recurrence of gastric cancer. RESULTS: Peritoneal recurrence is the most
      common pattern in recurrence of gastric cancer. The main risk factors for
      recurrence of gastric cancer are tumor stage, including depth of tumor invasion
      and lymph node metastasis, and Borrmann classification. The prognosis of patients
      with recurrence is very poor, especially patients with peritoneal recurrence.
      Systemic chemotherapy is still the main treatment method for patients with
      recurrent cancer. If complete resection can be accomplished, some benefits may be
      obtained from surgery for recurrence. However, standard treatment for patients
      with recurrence has not yet been established. CONCLUSIONS: Early detection and
      diagnosis of recurrence is quite crucial for treatment and prognosis. The optimal
      therapeutic strategy for recurrence should be based on a multidisciplinary
      assessment and the patient's individual state and should involve combined
      therapy.

PMID- 22613658
TI  - Association between the eNOS gene polymorphisms and rheumatoid arthritis risk in
      a northern Chinese population.
AB  - BACKGROUND: Several genetic polymorphisms in the endothelial nitric oxide
      synthase (eNOS) gene are associated with the pathogenesis of rheumatoid arthritis
      (RA). The objective of the present study was to investigate whether the two SNPs
      (T-786C and G894T) of the eNOS gene are associated with rheumatoid arthritis risk
      in a northern Chinese population. METHODS: In this study, the eNOS genes T-786C
      and G894T were studied in 196 cases with rheumatoid arthritis and 201 healthy
      controls with gender, age and ethnicity matched. The two SNPs were genotyped
      using polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP). The analyses of association were statistically compared using the chi
      square test with SPSS software for Windows. RESULTS: The frequency of the -786C
      allele was significantly higher in the rheumatoid arthritis patients than in the
      healthy controls (19.64% vs. 14.18%, P < 0.05). However, the 894T allele of the
      eNOS gene was not increased in the rheumatoid arthritis patients compared to the
      healthy controls. CONCLUSIONS: Individuals with the -786CC genotype have an
      increased risk of rheumatoid arthritis. Further study with an increased sample
      size is necessary for the study of the role of this SNP in rheumatoid arthritis.

PMID- 22613660
TI  - Surgical treatment for vascular anomalies and tracheoesophageal compression.
AB  - BACKGROUND: Vascular rings are uncommon anomalies in which preferred strategies
      for diagnosis and management may vary among institutions. In this study, we
      reported our approach and a review of our 5-year experience. METHODS: From May
      2006 to April 2011, 45 children (31 boys) with vascular rings underwent surgical
      repair at Beijing Children's Hospital. Nineteen patients (26%) had associated
      heart anomalies. RESULTS: There were two hospital deaths. At follow-up, 11
      patients still had intermittent respiratory symptoms, but these symptoms had no
      effect on growth or physical activities. No patients required reoperation.
      CONCLUSIONS: The rates of misdiagnosis and missed diagnosis of vascular rings are
      higher than those of other congenital heart diseases. A high index of clinical
      suspicion coupled with the use of computed tomography enables early diagnosis.
      Surgical repair can be performed successfully, although a number of patients will
      have persistent symptoms.

PMID- 22613659
TI  - Effects of television viewing on body fatness among Chinese children and
      adolescents.
AB  - BACKGROUND: Numerous studies have shown that time spent on television (TV)
      viewing is positively associated with obesity. The aim of this study was to
      examine the potential association between excessive TV viewing and obesity,
      especially abdominal obesity, among children and adolescents in mainland of
      China. METHODS: A total of 4708 children and adolescents aged 6 to 16 years were
      recruited for the study. Anthropometric measures were conducted by trained
      personnels. A self-report questionnaire was designed to gather information on TV
      time, physical activity, diet habits, maternal body mass index (BMI), birth
      weight, and on general demographics, including age and gender, and socio-economic
      status. RESULTS: The prevalence of obesity in this group was 6.5%. Linear
      regression analysis indicated that high TV viewing time (>= 1.5 h/d) was
      significantly associated with higher BMI, waist circumference (WC), and waist-to
      height ratio (WHtR). In addition, the high TV time group had 1.3 times the odds
      of obesity as compared to the low TV time group. Likewise, high TV viewing time
      increased the OR value 1.32 and 1.21 times higher in WC- and WHtR-defined
      obesity. Within the non-obesity group, high TV viewing time was also positively
      associated with higher WC and WHtR. All these correlations remained significant
      after adjustment for the confounding variables. CONCLUSIONS: Excessive TV viewing
      might increase the risk of obesity among Chinese youth. Reducing TV viewing time
      may be beneficial to improve health outcomes, both in the short- and long term.
      This finding should be taken into account in future designs of intervention
      policies to prevent childhood and adolescent obesity in China.

PMID- 22613661
TI  - Symptomatic hyponatremia and hyperglycemia complicating hysteroscopic resection
      of intrauterine adhesion: a case report.
AB  - Hysteroscopic surgery is a minimally invasive procedure for the treatment of
      intrauterine pathologies. However, it can result in fatal complications. We
      herein report a case of symptomatic hyponatremia and hyperglycemia during
      hysteroscopic resection of severe intrauterine adhesion with 5% dextrose in water
      as the distension medium. Because of the difficulty of the incision, the infusion
      pressure was 100 to 150 mmHg, and surgery was continued for 70 minutes. A total
      of 19 L of 5% dextrose in water was used as an irrigating fluid. Large-scale
      absorption of irrigating fluid (3 L) induced dilutional hyponatremia (120 mmol/L)
      and hyperglycemia (30 mmol/L). Initial signs were abnormal flatulence and
      postoperative coma. Hypertonic saline, diuretics, insulin, and liquid restriction
      were the prevailing treatment strategies for hyponatremia and hyperglycemia.
      Ionized calcium and potassium levels decreased during treatment. We emphasize the
      importance of prevention, recognition, and a meticulous perioperative treatment
      standard. Surgical teams must be vigilant in fluid deficit monitoring and serum
      electrolyte analysis.

PMID- 22613662
TI  - A novel SMPD1 mutation in two Chinese sibling patients with type B Niemann-Pick
      disease.
AB  - Type B Niemann-Pick disease is an autosomal recessive sphingolipidosis due to
      mutations in the sphingomyelin phosphodiesterase 1 gene (SMPD1). Here we present
      molecular findings for two sibling patients. One mutation V36A due to c.107T>C in
      exon 1 is a single nucleotide polymorphism and the other N522S due to c.1565 A>G
      in exon 6 is a novel missense mutation. This non-fatal missense mutation leads to
      -20% residual lysosomal acid sphingomyelinase activity in vitro and only results
      in hepatosplenomegaly without neurologic involvement.

PMID- 22613663
TI  - Dural enhancement detected by magnetic resonance imaging reflecting the
      underlying causes of cerebral venous sinus thrombosis.
AB  - Dural enhancement detected by magnetic resonance imaging is a common finding in
      patients with cerebral venous sinus thrombosis (CVST) and is usually interpreted
      as a change secondary to CVST. We report two cases of CVST with intense and
      diffuse dural enhancement that resulted from pachymeningitis in one patient and
      spontaneous intracranial hypotension in another. Pachymeningitis and spontaneous
      intracranial hypotension were also determined to be the underlying causes of
      CVST. The clinical data of these two patients are described. In patients with
      CVST, dural enhancement is not always a secondary change to CVST. It can be a
      manifestation of the underlying causes of CVST. When diffuse and intense dural
      enhancement is revealed, sufficient ancillary tests are warranted to rule out
      other potential pathological changes of the dura mater those can result in CVST.

PMID- 22613664
TI  - Sequential bilateral central retinal artery occlusion as the primary
      manifestation of systemic lupus erythematosus.
AB  - Bilateral central retinal artery occlusion (CRAO) has been rarely reported as the
      primary manifestation in patients with systemic lupus erythematosus (SLE). The
      severe retinal vaso-occlusive diseases usually cause devastating and permanent
      damage to visual function in spite of vigorous treatment. A 42-year-old Chinese
      woman presented with abrupt bilateral vision loss. The diagnosis of bilateral
      CRAO was suggested by the ocular presentation and fluorescein angiography.
      Laboratory studies showed positive results of antinuclear antibody, anti-Ro/SSA
      anti-La/SSB; decreased levels of C3, C4 complement and normal levels of
      antiphospholipides antibodies (APAs). Her visual acuity deteriorated despite
      systemic steroid and immunosuppressant treatment. Severe vaso-occlusive
      retinopathy may be an earlier manifestation of SLE without elevated level of
      APAs.

PMID- 22613665
TI  - Is it safe to monitor oesophageal temperature during AF ablation?

PMID- 22613666
TI  - Eric Willem Roubos, Ph.D., profiles in comparative endocrinology.

PMID- 22613667
TI  - NMR study of ligand release from asialoglycoprotein receptor under solution
      conditions in early endosomes.
AB  - Asialoglycoprotein receptor (ASGP-R) is an endocytic C-type lectin receptor in
      hepatocytes that clears plasma glycoconjugates containing a terminal galactose or
      N-acetylgalactosamine. The carbohydrate recognition domain (CRD) of ASGP-R has
      three Ca(2+)  binding sites (sites 1, 2 and 3), with Ca(2+)  at site 2 being
      directly involved in ligand binding. Following endocytosis, the ligands are
      released from ASGP-R in endosomes to allow receptor recycling to the cell
      membrane. Although dissociation of the receptor-ligand complex is mediated by the
      acidic environment within the mature endosomes, many of these complexes also
      dissociate in the early time of endocytosis, where pH is approximately neutral.
      To investigate the mechanism of ligand release from ASGP-R in early endosomes, we
      examined the binding mode of Ca(2+)  and ligands to ASGP-R CRD by NMR. We
      demonstrate that sites 1 and 2 of ASGP-R are high affinity Ca(2+)  binding sites,
      site 3 is low affinity, and that Ca(2+)  ions bind to sites 1 and 2
      cooperatively. The pH and Ca(2+)  concentration dependences of Ca(2+)  binding
      states indicated that early endosome conditions favor apo-ASGP-R CRD, allowing
      ligand release. Our results elucidated that the cooperative binding mode of
      Ca(2+)  makes it possible for ASGP-R to be more sensitive to Ca(2+) 
      concentrations in early endosomes, and plays an important role in the efficient
      release of ligand from ASGP-R. In our proposed mechanism, ASGP-R can rapidly
      release Ca(2+)  and its ligand even at nearly neutral pH. Sequence comparisons of
      endocytic C-type lectin receptors suggest that this mechanism is common in their
      family.

PMID- 22613668
TI  - Mycobacterium bovis infection in badger cubs: re-assessing the evidence for
      maternally derived immunological protection from advanced disease.
AB  - The Eurasian badger (Meles meles) is a significant source of bovine tuberculosis
      in cattle in the UK and Ireland. Protection from infectious diseases, arising
      from maternal antibody transfer, is a well-established immunological phenomenon
      in mammals. In a previous study of wild badgers, transient serological responses
      in cubs were taken as evidence of maternal antibody transfer, and it was
      speculated this conferred protection from subsequent mycobacterial excretion
      following acquisition of tuberculosis. However successful defence against
      mycobacterial infections is likely to be dominated by a cell-mediated response.
      Using a substantially larger dataset from the same badger population, we
      revisited the hypothesis of maternally derived protection. Whilst we found a
      significant association between transient serological responses and absence of
      subsequent Mycobacterium bovis excretion, the likelihood of detection of such
      responses was not significantly associated either with badger age, or with
      infection in the breeding females within a cub's natal group. We concluded that
      although maternal antibody transfer in badgers almost certainly occurs, transient
      serological responses represent an invalid proxy, and the reduced likelihood of
      M. bovis excretion associated with transient responses was more likely to be due
      to the lower sensitivity of the Brock ELISA test in detecting badgers with less
      advanced disease.

PMID- 22613669
TI  - Functional genetic polymorphisms from phase-II drug metabolizing enzymes.

PMID- 22613670
TI  - Molecular phylogenetics of a South Pacific sap beetle species complex
      (Carpophilus spp., Coleoptera: Nitidulidae).
AB  - Several species of sap beetles in the genus Carpophilus are minor pests of fresh
      produce and stored products, and are frequently intercepted in biosecurity
      operations. In the South Pacific region, the superficially similar species C.
      maculatus and C. oculatus are frequently encountered in these situations. Three
      subspecies of C. oculatus have been described, and the complex of these four taxa
      has led to inaccurate identification and questions regarding the validity of
      these taxa. A molecular phylogenetic study using the mitochondrial gene
      cytochrome c oxidase I (COI) and two nuclear markers comprising the rDNA internal
      transcribed spacer 2 (ITS2) and the D1-D2 region of the large (28S) ribosomal RNA
      subunit showed that C. maculatus, and C. o. cheesmani were easily differentiated
      from the two other subspecies of C. oculatus. COI also showed differentiation
      between C. o. gilloglyi and C. o. oculatus, but this was not shown when third
      codon positions were removed and when RY-coding analyses were conducted.
      Generalised mixed Yule-Coalescent (GMYC) models were fitted to trees estimated
      from the COI data and were analysed using a multimodel approach to consider the
      evidence for three taxonomic groupings of the C. oculatus group. While the
      arrangement with the highest cumulative weight was not the arrangement ultimately
      accepted, the accepted taxonomy also had an acceptable level of support. ITS2
      showed structure within C. oculatus, however C. o. oculatus was resolved as
      paraphyletic with respect to C. o. gilloglyi. COI showed evidence of sequence
      saturation and did not adequately resolve higher relationships between species
      represented in the dataset. 28S resolved higher relationships, but did not
      perform well at the species level. This study supports the validity of C.
      maculatus as a separate species, and provides sufficient evidence to raise C. o.
      cheesmani to the level of species. This study also shows significant structure
      within and between C. o. gilloglyi and C. o. oculatus, giving an indication of
      recent speciation events occurring. To highlight the interesting biology between
      these two taxa, C. o. gilloglyi is retained as a subspecies of C. oculatus. These
      results give clarity regarding the taxonomic status of C. maculatus and the
      subspecies of C. oculatus and provide a platform for future systematic research
      on Carpophilus.

PMID- 22613672
TI  - Curcumin for monoclonal gammopathies. What can we hope for, what should we fear?
AB  - Over the last decades there has been an increasing interest in a possible role of
      curcumin on cancer. Although curcumin is considered safe for healthy people,
      conclusive evidence on the safety and efficacy of curcumin for patients with
      monoclonal gammopathies is, so far, lacking. The present paper reviews the
      literature on molecular, cellular and clinical effects of curcumin in an attempt
      to identify, reasons for optimism but also for concern. The results of this
      critical evaluation can be useful for both patient- selection and monitoring in
      the context of clinical trials. Curcumin might be helpful for some but certainly
      not for all patients with monoclonal gammopathies. It is important to avoid
      unnecessary detrimental side effects in some in order to safeguard curcumin for
      those that could benefit. Parameters for patient monitoring, that can be used as
      early warning signs and as indicators of a favorable development have therefore
      been suggested.

PMID- 22613671
TI  - Usability and performance of a wearable tele-echography robot for focused
      assessment of trauma using sonography.
AB  - Focused Assessment with Sonography for Trauma (FAST) is widely used as a first
      lifesaving step for patients suffering from internal bleeding. Because it may
      take a long time to transport such patients to a hospital, a wearable and
      portable tele-echography robot that a paramedic can attach to the patient has
      been developed. In the current study, experiments were conducted to evaluate the
      usability and performance of attached FAST. The proposed robot must be attached
      to 4 areas to perform FAST. The time required for attachment and the positions of
      attachment completed by 9 non-medical staff members, as well as the time it took
      for the FAST to reach a medical doctor, were measured. The echo images obtained
      when the patient's body was in motion were evaluated by a medical doctor. The
      robot could be attached to all 4 areas within approximately 5min, and the maximum
      gap was 4.8cm. This indicates that a paramedic who has received training in
      emergency medical care should be able to attach the robot to a patient quickly
      and accurately. Additionally, it was confirmed that the robot could be used to
      complete FAST under a doctor's control within 9min and that the extracted echo
      images were suitable for FAST. A comparison of the results with current ambulance
      transportation time confirmed that FAST could be completed approximately 14min
      before the patient reached the hospital. The results of the current study
      indicate that the robot is worth using, is suitable for FAST, and will be
      effective in emergency medical care.

PMID- 22613673
TI  - Growth, energetics and the cortisol-hepatic glucocorticoid receptor axis of
      medaka (Oryzias latipes) in various salinities.
AB  - We examined growth of euryhaline Japanese medaka (Oryzias latipes) after transfer
      to freshwater or seawater from isotonic saline. Growth was unaffected by the
      different salinities for 1 week, but the body weight increase and BMI of fish
      kept in freshwater for 2-3 weeks were significantly higher than those in the
      isotonic controls. These results may reflect the usual habitat of this species.
      To assess the basis for the difference in growth, energetics and the hepatic
      stress axis were evaluated 1 week after the transfer. Unexpectedly, despite the
      higher growth rate, the rate of routine oxygen consumption was significantly
      higher in freshwater. Plasma cortisol levels in freshwater were significantly
      higher than those in seawater, and the mRNA levels of the glucocorticoid receptor
      (GR1) in the liver were significantly lower in freshwater and seawater, compared
      to that in isotonic saline. Branchial Na(+)/K(+)-ATPase activities were also
      reduced significantly in freshwater and seawater, compared to that in isotonic
      saline. The higher levels of hepatic GR1 expression and branchial Na(+)/K(+)
      ATPase activity in isotonic salinity than those in freshwater and seawater for 1
      week may account for the lower growth rate under the isotonic condition. After 3
      weeks, however, the Na(+)/K(+)-ATPase activity in seawater was significantly
      higher than that in freshwater. No significant difference in growth rate between
      freshwater and seawater groups indicates that medaka is a good model for studies
      of hypo- and hyperosmotic adaptations, since osmoregulation is not strongly
      associated with size and growth.

PMID- 22613674
TI  - Development and validation of an efficient in-house real-time reverse
      transcription polymerase chain reaction assay for the quantitative detection of
      serum hepatitis delta virus RNA in a diverse South London population.
AB  - Hepatitis delta virus (HDV) causes both acute and chronic hepatitis, always in
      the presence of hepatitis B. Analysis of global HDV isolates has shown that at
      least eight genotypes exist. HDV RNA quantitation and genotyping are important
      tools in the diagnosis and management of infected individuals. There is, as yet,
      no commercially available quantitative HDV RNA assay. Several laboratories have
      developed in-house assays, but equivalent detection and quantitation across all
      HDV genotypes has not been demonstrated. In this study, the development of an in
      house real-time reverse transcription polymerase chain reaction (RT PCR) assay is
      described to quantify HDV RNA in serum or plasma. Its efficiency was validated by
      testing 99 samples from patients with known chronic HDV infection, along with 22
      samples from individuals without HDV. The assay has a dynamic range of 6.4*10(2)
      to 6.4*10(8)copies/mL. Amplicons of the quantitative PCR can be directly used for
      sequence analysis and genotyping. HDV-1, HDV-5 and HDV-6 were identified,
      reflecting the areas of origin of our cohort of patients. The ability to genotype
      and to accurately quantify HDV RNA levels in the more recently discovered African
      genotypes will be important for investigating the natural history of HDV in this
      group, compared to those with genotype 1 disease.

PMID- 22613675
TI  - Comparison of three different methods for the evaluation of IL28 and ITPA
      polymorphisms in patients infected with HCV.
AB  - A single nucleotide polymorphism (SNP) upstream of the IL28 gene (rs12979860) has
      been reported to predict sustained virological response to peginterferon
      ribavirin therapy in chronic HCV patients. In addition, two functionally
      deficient variants (rs1127354 and rs7270101) of inosine triphosphatase (ITPA)
      were shown to protect against ribavirin (RBV) - induced hemolytic anemia during
      early stages of treatment. In this study, three methods for detecting IL28 and
      ITPA mutations were compared to evaluate accuracy, sensitivity costs and turn
      around time. IL28 and ITPA variants were detected using genomic DNA from
      peripheral blood mononuclear cells (PBMCs) of 61 patients with chronic HCV
      infection by denaturing high-performance liquid chromatography (DHPLC), direct
      DNA sequencing analysis and Taq Man Real-Time SNP analysis. Complete concordance
      in the IL28 polymorphism analysis was observed among the three methods. As for
      ITPA polymorphisms, 60/61 (98.4%) samples were consistent among the three
      methods, while results for 1/61 (1.64%) samples were concordant by DHPLC and
      sequencing, and discordant by real-time SNP. All three methods are suitable for
      routine testing. On the other hand, screening by real-time SNP detection was less
      expensive and more rapid.

PMID- 22613676
TI  - Immunosuppressive drugs on inducing Ag-specific CD4(+)CD25(+)Foxp3(+) Treg cells
      during immune response in vivo.
AB  - A variety of immunosuppressive drugs are currently used in patients with allo
      grafts or autoimmune diseases. Though the effects of rapamycin (RPM) and other
      immunosuppressant on the CD4(+)CD25(+)Foxp3(+) T regulatory cells (Tregs) were
      studied, their impact on Ag-specific Tregs during immune response was not well
      defined. In our studies, we adoptively transferred TCR-transgenic CD4(+)KJ1-26(+)
      T cells, CD4(+)KJ1-26(+)CD25(-) naive T cells or CD4(+)KJ1-26(+)CD25(+) Tregs
      into syngeneic BALB/c mice. 24h later, we treated the recipients with OVA
      immunization and immunosuppressant including rapamycin (RPM), fingolimod
      (FTY720), cyclosporin A (CsA), mycophenolate mofetil (MMF), leflunomide (LEF),
      cyclophosphamide (Cy) or none, respectively. The levels and function of CD4(+)KJ1
      26(+)CD25(+)Foxp3(+) Tregs in draining lymph nodes (dLNs) and spleens were
      determined at different time points. Significantly higher percentage and cell
      number of Ag-specific CD4(+)KJ1-26(+)CD25(+)Foxp3(+) Tregs were observed in OVA
      immunized mice treated with RPM or FTY720 compared with mice that received OVA
      immunization alone. Furthermore, RPM augmented the population of functional
      iTregs in dLNs and spleens whereas inhibited nTregs during immune response. In
      contrast to RPM and FTY720, MMF, LEF, CsA, and Cy markedly decreased the levels
      of Ag-specific CD4(+)KJ1-26(+)CD25(+)Foxp3(+) Tregs during immune response. Thus,
      different immunosuppressive drugs have distinct effects on the Ag-specific
      CD4(+)CD25(+)Foxp3(+) Tregs during immune response. The stronger inhibiting
      effects of MMF, LEF, CsA and Cy on CD4(+)CD25(+)Foxp3(+) Tregs than on T
      effectors may block the host immune tolerance potentiality.

PMID- 22613678
TI  - A new journal... on spindle cells.
AB  - Welcome to Clinical Sarcoma Research a new open access, online medical journal
      providing a forum for clinical knowledge on rare solid cancers - sarcomas. We
      believe there is a vacuum, which this effort may hope to fill at least in part.
      Indeed, we ought to share first-hand medical experience and clinically meaningful
      translational ideas much more within the sarcoma community worldwide. This
      journal is intended to be one of the many tools we need for this purpose.

PMID- 22613677
TI  - Beneficial effects of non-matched allogeneic cord blood mononuclear cells upon
      patients with idiopathic osteoporosis.
AB  - BACKGROUND: Immunological arguments and historical examples have shown that
      treatment with cord blood for non-hematopoietic activities, such as growth factor
      production and stimulation of angiogenesis, may not require matching or immune
      suppression. METHODS: To study the benefit of blood mononuclear cell therapy, 8
      patients with idiopathic osteoporosis were given intermittent treatments with non
      matched allogeneic cord blood mononuclear cells for 3 months. Morning fasting
      samples were collected for measuring urine N telopeptide of type-1 collagen,
      serum bone-specific alkaline phosphatase, and insulin-like growth factor 1 during
      one-year study. RESULTS: Clinical response was striking. Serum insulin-like
      growth factor 1 significantly increased in all patients at 3 months compared with
      baseline values, from 264.1 +/- 107.0 to 384.4 +/- 63.1 ng/mL (P = 0.002), with a
      tendency to return to baseline values at 12 months (312.9 +/- 75.5 ng/mL, P =
      0.083). In contrast, differences in serum bone-specific alkaline phosphatase and
      urine N telopeptide of type-1 collagen were not significant at 3 (P = 0.765, P =
      0.057) or 12 months (P = 0.889, P = 0.122). A beneficial effect on bone density
      was observed in all patients at the lumbar spine. The mean bone mineral density
      calculated during therapy (0.6811 +/- 0.1442 g/cm(2)) tended higher than baseline
      values (0.6239 +/- 0.1362 g/cm(2), P < 0), and percentage change (median) varied
      from 8.85% at 3 months to 7.85% at one year. All patients are now well after one
      year. CONCLUSIONS: The findings indicate that for these patients with idiopathic
      osteoporosis, treatment with cord blood mononuclear cells led to a significant
      increase in insulin-like growth factor 1 levels, which favors the increase in
      bone mineral density.

PMID- 22613679
TI  - Using mice to unveil the genetics of cancer resistance.
AB  - In the UK, four in ten people will develop some form of cancer during their
      lifetime, with an individual's relative risk depending on many factors, including
      age, lifestyle and genetic make-up. Much research has gone into identifying the
      genes that are mutated in tumorigenesis with the overwhelming majority of
      genetically-modified (GM) mice in cancer research showing accelerated
      tumorigenesis or recapitulating key aspects of the tumorigenic process. Yet if
      six out of ten people will not develop some form of cancer during their lifetime,
      together with the fact that some cancer patients experience spontaneous
      regression/remission, it suggests there are ways of 'resisting' cancer. Indeed,
      there are wildtype, spontaneously-arising mutants and GM mice that show some form
      of 'resistance' to cancer. Identification of mice with increased resistance to
      cancer is a novel aspect of cancer research that is important in terms of
      providing both chemopreventative and therapeutic options. In this review we
      describe the different mouse lines that display a 'cancer resistance' phenotype
      and discuss the molecular basis of their resistance.

PMID- 22613680
TI  - Epithelial E- and P-cadherins: role and clinical significance in cancer.
AB  - E-cadherin and P-cadherin are major contributors to cell-cell adhesion in
      epithelial tissues, playing pivotal roles in important morphogenetic and
      differentiation processes during development, and in maintaining integrity and
      homeostasis in adult tissues. It is now generally accepted that alterations in
      these two molecules are observed during tumour progression of most carcinomas.
      Genetic or epigenetic alterations in E- and P-cadherin-encoding genes (CDH1 and
      CDH3, respectively), or alterations in their proteins expression, often result in
      tissue disorder, cellular de-differentiation, increased invasiveness of tumour
      cells and ultimately in metastasis. In this review, we will discuss the major
      properties of E- and P-cadherin molecules, its regulation in normal tissue, and
      their alterations and role in cancer, with a specific focus on gastric and breast
      cancer models.

PMID- 22613681
TI  - Tuberculosis care: why the words we use matter.

PMID- 22613682
TI  - Declaration on palliative care and MDR/XDR-TB.

PMID- 22613683
TI  - Language in tuberculosis services: can we change to patient-centred terminology
      and stop the paradigm of blaming the patients?
AB  - The words 'defaulter', 'suspect' and 'control' have been part of the language of
      tuberculosis (TB) services for many decades, and they continue to be used in
      international guidelines and in published literature. From a patient perspective,
      it is our  opinion that these terms are at best inappropriate, coercive and
      disempowering, and at worst they could be perceived as judgmental and
      criminalising, tending to place the blame of the disease or responsibility for
      adverse treatment outcomes on one side-that of the patients. In this  article,
      which brings together a wide range of authors and institutions from Africa, Asia,
      Latin America, Europe and the Pacific, we discuss the use of the words
      'defaulter', 'suspect' and 'control' and argue why it is detrimental to continue
      using them  in the context of TB. We propose that 'defaulter' be replaced with
      'person lost to follow-up'; that 'TB suspect' be replaced by 'person with
      presumptive TB' or 'person to be evaluated for TB'; and that the term 'control' 
      be replaced with 'prevention and care' or simply deleted. These terms are non
      judgmental and patient-centred. We appeal to the global Stop TB Partnership to
      lead discussions on this issue and to make concrete steps towards changing the
      current paradigm.

PMID- 22613685
TI  - 2011: the year in review. part I: tuberculosis.
AB  - IN THIS YEAR-IN-REVIEW ARTICLE, we summarizes 104 articles published on
      tuberculosis in the International Journal of Tuberculosis and Lung Disease from
      the January to the August issue in 201, and arbitrarily categorise them according
      to three subject areas: active TB, latent TB infection (LTBI),and operational
      research.

PMID- 22613684
TI  - The chemotherapy of tuberculosis: past, present and future.
AB  - The history of the development of modern chemotherapy for tuberculosis (TB),
      largely due to the British Medical Research Council, is first described. There is
      a current need to shorten the duration of treatment and to prevent and cure drug
      resistant disease. These aims will only be  achieved if the way in which
      multidrug treatment prevents resistance from emerging and the reasons for the
      very slow response to chemotherapy are understood. Consideration of mutation
      rates to resistance and the size of bacterial populations in lesions makes it
      very unlikely that resistance  would emerge spontaneously, leaving irregularity
      in drug taking and inadequate dosage as the main reasons for its occurrence. Slow
      response to treatment seems due to the presence of persister populations whose
      natural history is only partly known. In the future, we need to explore the
      persister  state in patients and in experimental murine TB, and to take it into
      account in the design of future mouse experiments. The activity of rifamycins and
      pyrazinamide is being increased by a rise in rifamycin dosage and the inhalation
      of pyrazinoic acid. New drugs are gradually being brought  into use, initially
      TMC207 and the nitroimadazoles, PA824 and OPC67683. They will need to be tested
      in new combination regimens for drug-susceptible and multi- and extensively drug
      resistant disease.

PMID- 22613686
TI  - Direct costs of pulmonary tuberculosis among patients receiving treatment in
      Bauchi State, Nigeria.
AB  - BACKGROUND: To access tuberculosis (TB) services, patients have to bear the costs
      of out-of-pocket expenditures or direct costs for transport, drugs and other
      services that are not provided free-of-charge. These costs could represent a
      barrier to care, especially in a country such as  Nigeria, where per capita gross
      national income is only US$1160 and 46% of the urban population live below the
      poverty line. OBJECTIVE: To describe the direct costs of TB diagnosis and
      treatment in Bauchi State, Nigeria, from the patient's perspective. METHODS: A
      cross-sectional  study. A sample size of 255 patients was randomly selected from
      27 of 67 facilities in Bauchi State, Nigeria. RESULTS: The median out-of-pocket
      cost for hospitalised patients was estimated at US$166.11, while ambulatory
      patients paid an estimated median cost of US$94.16, equivalent  to about 9-38% of
      their average annual income. Female patients spent a higher proportion of their
      income on diagnosis and treatment than males (P < 0.0001). The median out-of
      pocket costs borne by patients before, during and after diagnosis were estimated
      at respectively US$35.23,  US$27.12 and US$23.43 for ambulatory patients, and
      additional average out-of-pocket spending of US$66.44 for patients hospitalised
      during their illness. Pre-diagnosis, diagnosis and post-diagnosis out-of-pocket
      spending did not vary significantly by human immunodeficiency  virus status (P >
      0.05) and sex (P > 0.05). CONCLUSION: The costs of anti-tuberculosis treatment
      found in this study are expensive and potentially catastrophic for many patients
      and their families.

PMID- 22613687
TI  - Emergence of totally drug-resistant tuberculosis: obscure and overlooked issues.

PMID- 22613688
TI  - Comparison of anterior chamber depth measurements by 3-dimensional optical
      coherence tomography, partial coherence interferometry biometry, Scheimpflug
      rotating camera imaging, and ultrasound biomicroscopy.
AB  - PURPOSE: To evaluate the congruity of anterior chamber depth (ACD) measurements
      using 4 devices. SETTING: Saneikai Tsukazaki Hospital, Himeji City, Japan.
      DESIGN: Comparative case series. METHODS: In 1 eye of 42 healthy participants,
      the ACD was measured by 3-dimensional corneal and anterior segment optical
      coherence tomography (CAS-OCT), partial coherence interferometry (PCI),
      Scheimpflug imaging, and ultrasound biomicroscopy (UBM). The differences between
      the measurements were evaluated by 2-way analysis of variance and post hoc
      analysis. Agreement between the measurements was evaluated using Bland-Altman
      analysis. To evaluate the true ACD using PCI, the automatically calculated ACD
      minus the central corneal thickness measured by CAS-OCT was defined as PCI true.
      Two ACD measurements were also taken with CAS-OCT. RESULTS: The mean ACD was 3.72
      mm +/- 0.23 (SD) (PCI), 3.18 +/- 0.23 mm (PCI true), 3.24 +/- 0.25 mm
      (Scheimpflug), 3.03 +/- 0.25 mm (UBM), 3.14 +/- 0.24 mm (CAS-OCT auto), and 3.12
      +/- 0.24 mm (CAS-OCT manual). A significant difference was observed between PCI
      biometry, Scheimpflug imaging, and UBM measurements and the other methods. Post
      hoc analysis showed no significant differences between PCI true and CAS-OCT auto
      or between CAS-OCT auto and CAS-OCT manual. Strong correlations were observed
      between all measurements; however, Bland-Altman analysis showed good agreement
      only between PCI true and Scheimpflug imaging and between CAS-OCT auto and CAS
      OCT manual. CONCLUSION: The ACD measurements obtained from PCI biometry,
      Scheimpflug imaging, CAS-OCT, and UBM were significantly different and not
      interchangeable except for PCI true and CAS-OCT auto and CAS-OCT auto and CAS-OCT
      manual. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest
      in any material or method mentioned.

PMID- 22613689
TI  - Iris-fixated toric phakic intraocular lens for myopic astigmatism.
AB  - PURPOSE: To evaluate the efficacy, predictability, safety, stability, and
      complications of the Artiflex toric iris-fixated phakic intraocular lens (pIOL)
      for myopic astigmatism. SETTING: Private practice surgery centers, Valencia and
      Terrassa, Spain. DESIGN: Cohort study. METHODS: At 12 months, refraction,
      uncorrected (UDVA) and corrected (CDVA) distance visual acuities, complications,
      pIOL misalignment, and endothelial cell count (ECC) were evaluated. Indices of
      success and misalignment were calculated using vector analysis. RESULTS: The
      study enrolled 42 eyes in 25 patients aged 21 to 39 years. The mean spherical
      equivalent decreased from -8.85 diopters (D) +/- 2.71 (SD) to -0.37 +/- 0.46 D,
      with 66.7% of the eyes within +/- 0.50 D. The mean cylinder power decreased from 
      2.90 D (range -1.50 to -5.00 D) to -0.39 D (range 0.00 to -1.50 D); refraction
      was highly stable. All eyes achieved a decimal UDVA of 0.5 or better and a CDVA
      of 0.8 or better. A gain of 1 line or more of CDVA was found in 69.1% of eyes.
      The mean clinical pIOL misalignment was 2.6 +/- 1.8 degrees; 1 eye (2.4%)
      required surgical repositioning of the pIOL. The mean ECC decrease was 9.3% +/-
      1.8%; iris pigment precipitates were observed in 16.7% of eyes. Vector analysis
      showed excellent mean indices of success for overall (0.94 +/- 0.04), spherical
      (0.96 +/- 0.05), and astigmatic (0.95 +/- 0.16) corrections; the mean angle of
      error was 1.8 +/- 2.7 degrees. CONCLUSION: Implantation of the toric pIOL was
      effective, predictable, safe, and stable for the correction of myopic
      astigmatism. FINANCIAL DISCLOSURE: No author has a financial or proprietary
      interest in any material or method mentioned.

PMID- 22613690
TI  - Clinical effectiveness, cost-effectiveness and service users' perceptions of
      early, well-resourced communication therapy following a stroke: a randomised
      controlled trial (the ACT NoW Study).
AB  - OBJECTIVE: To determine the clinical effectiveness, cost-effectiveness and
      service users' views of enhanced early communication therapy by speech and
      language (SL) therapists compared with attention control (AC). DESIGN: Successful
      feasibility study followed by a randomised trial with economic evaluation, and
      nested qualitative study using 32 individual interviews. SETTING: Twelve English
      NHS hospital and community stroke services. PARTICIPANTS: One hundred and seventy
      adults with aphasia or dysarthria admitted to hospital with stroke, December 2006
      to January 2010. Eligibility determined by NHS SL therapists. Seventeen people
      declined follow-up. INTERVENTIONS: A best-practice, flexible intervention by NHS
      SL therapists, up to three contacts per week for up to 16 weeks compared with a
      similar number of AC contacts by employed visitors. MAIN OUTCOME MEASURES:
      Primary outcome was blinded, functional communicative ability 6 months post
      randomisation on the Therapy Outcome Measure activity subscale (TOM). Secondary
      outcomes were participants' perceptions on the Communication Outcomes After
      Stroke scale (COAST); carers' perceptions of participants from part of the Carer
      COAST; carer well-being on Carers of Older People in Europe Index and quality-of
      life items from Carer COAST. Serious adverse events (SAEs) were recorded.
      Economic evaluation: participants' utility (European Quality of Life-5
      Dimensions), service use and cost data from medical records and carers, and a
      discrete choice experiment. RESULTS: Intervention typically started after 2
      weeks, providing 22 contacts. Both groups improved on the TOM. The estimated 6
      months' group difference [95% confidence interval (CI)] was 0.25 (-0.19 to 0.69)
      points in favour of SL therapy. Sensitivity analyses adjusting for baseline
      chance imbalance or not imputing values for decedents further reduced this
      difference. Per-protocol analyses rejected a possible dilution of therapy from
      controls refusing allocation and receiving NHS SL therapy. There was no evidence
      of added benefit of therapy on any secondary outcome measure or SAEs, although
      the latter were less frequent in the therapy group [odds ratio 0.42 (95% CI 0.16
      to 1.1)]. Regardless of group allocation, interviewed participants reported
      positive impacts on their confidence and mood, identified drivers for change and
      valued early and sustained contact. Health economic analysis indicated a high
      level of uncertainty. Early enhanced SL therapy for communication is likely to be
      cost-effective only if decision-makers are prepared to pay >= L25,000 to gain one
      unit of utility. CONCLUSIONS: These findings exclude the possibility of a
      clinically significant difference of 0.5 points on the TOM. There was no
      evidence, on any measure, of added benefit of early communication therapy beyond
      that from AC. It is unclear whether therapy is more or less cost-effective than
      AC. Early, frequent contact was highly valued by users and had good uptake.
      Functional communication improved for both groups, plausibly due to natural
      recovery and early and regular opportunity to practise everyday communication
      with a professional (therapist/visitor). There is no evidence to recommend
      enhancing the provision of early communication therapy by a qualified SL
      therapist over and above usual care. SL therapy service reorganisation should
      consider skill mix and timing within a stepped care model and should take place
      within the context of a trial.

PMID- 22613691
TI  - Clinical application of full-face, whole, full-thickness skin grafting: a case
      report.
AB  - A considerable portion of burn patients suffers severe full-face burns. Even
      after they were treated, some severe abnormalities still stay with them such as
      upper- and lower-eyelid ectropions, upper- and lower-lip ectropions, microstomia
      and extensive facial scar hyperplasia accompanied with pruritus. Patients suffer
      a great deal physically, emotionally and socially. Here we conclude our treatment
      experience of full-face burns with the full-face, whole, full-thickness skin
      grafting, which has not yet reported in the literature. We transplanted a whole,
      full-thickness skin graft to cover the wound in the primary operation and then
      remedied eyelid ectropions and microstomia in the operation that followed. The
      results of a 4-year-follow-up suggest that the patient has recovered part of
      facial expression and sensation without any geographic scars. Full-face, whole,
      full-thickness skin grafting appears to be an effective and relatively simple
      method for full-face burns that do not respond well to facial composite tissue
      allotransplantation (CTA).

PMID- 22613692
TI  - Practice of excessive F(IO(2)) and effect on pulmonary outcomes in mechanically
      ventilated patients with acute lung injury.
AB  - BACKGROUND: Optimal titration of inspired oxygen is important to prevent
      hyperoxia in mechanically ventilated patients in ICUs. There is mounting evidence
      of the deleterious effects of hyperoxia; however, there is a paucity of data
      about F(IO(2)) practice and oxygen  exposure among patients in ICUs. We therefore
      sought to assess excessive F(IO(2)) exposure in mechanically ventilated patients
      with acute lung injury and to evaluate the effect on pulmonary outcomes. METHODS:
      From a database of ICU patients with acute lung injury identified  by prospective
      electronic medical record screening, we identified those who underwent invasive
      mechanical ventilation for > 48 hours from January 1 to December 31, 2008.
      Ventilator settings, including F(IO(2)) and corresponding S(pO(2)), were
      collected  from the electronic medical record at 15-min intervals for the first
      48 hours. Excessive F(IO(2)) was defined as F(IO(2)) > 0.5 despite S(pO(2)) >
      92%. The association between the duration of excessive exposure and pulmonary
      outcomes  was assessed by change in oxygenation index from baseline to 48 hours
      and was analyzed by univariate and multivariate linear regression analysis.
      RESULTS: Of 210 patients who met the inclusion criteria, 155 (74%) were exposed
      to excessive F(IO(2)) for a median duration of  17 hours (interquartile range 7.5
      33 h). Prolonged exposure to excessive F(IO(2)) correlated with worse oxygenation
      index at 48 hours in a dose-response manner (P < .001.). Both exposure to higher
      F(IO(2)) and longer duration of exposure  were associated with worsening
      oxygenation index at 48 hours (P < .001), more days on mechanical ventilation,
      longer ICU stay, and longer hospital stay (P = .004). No mortality difference was
      noted. CONCLUSIONS: Excessive oxygen supplementation is common in mechanically
      ventilated  patients with ALI and may be associated with worsening lung function.

PMID- 22613693
TI  - Dietary antioxidants and periodontal disease in community-based older Japanese: a
      2-year follow-up study.
AB  - OBJECTIVE: To investigate the longitudinal relationship between the intake of
      dietary antioxidants and periodontal disease in community-dwelling older
      Japanese. DESIGN: A retrospective cohort study, with a follow-up of 2 years (2003
      2005). Intakes of dietary antioxidants (vitamin C, vitamin E, alpha-carotene and
      beta-carotene) were assessed with a validated FFQ. Participants were classified
      by tertile of antioxidant intake. Full-mouth periodontal status, measured as the
      clinical attachment level, was recorded at baseline and follow-up examinations.
      Periodontal disease progression was considered as loss of attachment of 3 mm or
      greater over the study period at the interproximal site for each tooth. Finally,
      the number of teeth with periodontal disease progression per person was
      calculated and was used as the outcome. Poisson regression analysis was
      conducted, with dietary antioxidants as the main exposure, to estimate their
      influence on the number of teeth with periodontal disease progression. SETTING:
      Niigata City (Japan). SUBJECTS: Dentate individuals aged 75 years in 2003, for
      whom data were available, were included in the analyses (n 264). RESULTS: A
      higher intake of dietary antioxidants was inversely associated with the number of
      teeth with periodontal disease progression, controlling for other variables. The
      multivariate-adjusted incidence rate ratios in the first, second and third
      tertiles were 1.00, 0.76 (95 % CI 0.60, 0.97) and 0.72 (95 % CI 0.56, 0.93) for
      vitamin C; 1.00, 0.79 (95 % CI 0.62, 0.99) and 0.55 (95 % CI 0.42, 0.72), for
      vitamin E; and 1.00, 1.02 (95 % CI 0.81, 1.29) and 0.73 (95 % CI 0.56, 0.95) for
      beta-carotene. CONCLUSIONS: The study results suggest that higher intake of
      antioxidants may mitigate periodontal disease in community-dwelling older
      Japanese.

PMID- 22613694
TI  - Changes in female sexual function following anterior with and without posterior
      vaginal mesh surgery for the treatment of pelvic organ prolapse.
AB  - INTRODUCTION: Comparison of female sexual function following anterior and total
      transvaginal mesh (TVM) surgery has never been reported. AIM: To compare the
      sexual function after anterior and total TVM repair for the treatment of pelvic
      organ prolapse (POP). MAIN OUTCOME MEASURES: The short forms of Urogenital
      Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7), and the
      Female Sexual Function Index (FSFI). METHODS: One hundred and sixty-five women
      with symptomatic POP stages II to IV defined by the POP quantification (POP-Q)
      staging system underwent TVM procedures at our hospitals. Seventy women were
      included because they were sexually active and had complete follow-up. All
      subjects were divided into the anterior group (anterior TVM; N=39) and total
      group (anterior and posterior TVM; N=31). Preoperative and postoperative
      assessments included pelvic examination using the POP-Q system, urodynamic study,
      and a personal interview to evaluate urinary and sexual symptoms with the short
      forms of UDI-6 and IIQ-7, and the FSFI. RESULTS: There was no difference between
      the two groups as for age, parity, diabetes, hypertension, concomitant
      procedures, and success rates for TVM and mid-urethral sling in this study
      (P>0.05). Regarding the POP-Q analysis, there was a significant improvement at
      points Aa, Ba, C, Ap, and Bp (P<0.05) in both groups except for total vaginal
      length (P>0.05). The preoperative scores of UDI-6 and IIQ-7 were significantly
      higher in the total group (P<0.01), and the UDI-6 and IIQ-7 scores showed
      significant decreases in both groups postoperatively (P<0.01). After TVM surgery,
      the score of the dyspareunia domain worsened significantly in both groups
      (P<0.05), and the deteriorated lubrication domain was noted only in the total
      group (P=0.042). CONCLUSIONS: TVM procedure creates an effective anatomical
      restoration of POP, but individual domains of FSFI may worsen. Compared with the
      anterior group, women of the total group had worse quality of life in term of
      urinary symptoms preoperatively, and experienced a greater sexual impairment on
      lubrication following surgery.

PMID- 22613695
TI  - Moral and scientific boundaries: research ethics on the Thai-Burma border.

PMID- 22613696
TI  - Commentary on 'Biodefence and the production of knowledge: rethinking the
      problem'.
AB  - Buchanan and Kelley provide a sophisticated and thoughtful critique of
      contemporary discussions of biosecurity. They provide sound critiques of American
      biodefence institutions, and the general sense of imminent threat underlying the
      rush to fund biodefence. However, the essay consistently misrepresents the
      breadth and depth of scholarly research on the ethics and politics of biodefence.

PMID- 22613697
TI  - Neuropeptide Y modulates calcium channels in hamster submandibular ganglion
      neurons.
AB  - It is established that neuropeptide Y (NPY) is a transmitter of parasympathetic
      secretory impulses in submandibular gland. The neuropeptides substance P,
      vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP)
      are likely mediators of secretory parasympathetic responses of the gland.
      Previously, we have shown that substance P, VIP and CGRP modulate voltage
      dependent Ca(2+) channels (VDCCs) in hamster submandibular ganglion (SMG)
      neurons. In this study, we attempt to characterize the effect of NPY on VDCCs
      current using Ba(2+) (I(Ba)) in SMG neurons. Application of NPY caused both
      facilitation and inhibition of L-type and N/P/Q-type I(Ba), respectively.
      Intracellular dialysis of the Galpha(s)-protein antibody attenuated the NPY
      induced facilitation of I(Ba). The adenylate cyclase (AC) inhibitor, as well as
      protein kinase A (PKA) inhibitor attenuated the NPY-induced facilitation of
      I(Ba). Intracellular dialysis of the Galpha(i)-protein antibody attenuated the
      NPY-induced inhibition of I(Ba). Application of a strong depolarizing voltage
      prepulse attenuated the NPY-induced inhibition of I(Ba). These results indicate
      that NPY facilitates L-type VDCCs via Galpha(s)-protein involving AC and PKA. On
      the other hand, NPY also inhibits N/P/Q-type VDCCs via Galpha(i)-protein
      betagamma subunits in the SMG neurons.

PMID- 22613698
TI  - Steroid-responsive focal epilepsy with focal dystonia accompanied by glutamate
      receptor delta2 antibody.
AB  - This report describes a rare case presenting with focal epilepsy and focal
      dystonia associated with glutamate receptor delta2 antibody. The patient was a 47
      year-old male patient with neurosyphilis. He presented with an intractable focal
      seizure spreading from the right arm, with dystonia of the left leg. The IgG
      antibody of glutamate receptor delta2 was detected. Ictal and interictal SPECT
      suggested focal epilepsy in the left frontal cortex. Antibiotic and antiepileptic
      drugs were ineffective, although steroid pulse therapy effectively diminished the
      patient's symptoms. Inflammatory mechanisms may have contributed to this
      disorder.

PMID- 22613699
TI  - Opportunistic infections in myasthenia gravis treated with mycophenolate mofetil.
AB  - Mycophenolate mofetil (MMF) is used for immunosuppression in myasthenia gravis
      (MG). Although there are numerous data on associated infection and prophylaxis in
      transplant patients who are on MMF, data in MG remains lacking. We report two
      elderly seropositive MG patients who developed cytomegalovirus (CMV) enteritis
      and Epstein-Barr virus (EBV) encephalitis while on MMF for 5months and 1year,
      respectively. Chronic MMF therapy in MG patients may trigger life-threatening
      infections including CMV and EBV diseases, especially in the elderly. Similar to
      the practice in transplant patients, viral serology testing and appropriate
      prophylactic regimen with antiviral agents should be considered, particularly in
      older MG patients.

PMID- 22613700
TI  - Type 1 immune response in progressive multiple sclerosis.
AB  - The aim of the study was to evaluate the type-1 immune response by analyzing T
      bet expression in circulating T and B cells in Primary Progressive (PP) and
      Secondary Progressive (SP) Multiple Sclerosis (MS) patients. We found higher
      percentages of circulating CD4+T-bet+ and CD8+T-bet+ T cells in SPMS and PPMS
      than in remitting-relapsing MS patients and controls. Moreover, in SPMS, we
      observed a positive correlation between the percentages of circulating CD4+T-bet+
      or CD8+T-bet+ T cells and disease severity. The increased percentages of Th1 and
      Tc1 cells suggest that MS progressive forms, unlike RRMS, are characterized by a
      permanent peripheral type-1 immune activation.

PMID- 22613701
TI  - Lipid-lowering therapy in chronic kidney disease: is there a role for ezetimibe?
AB  - The use of lipid-lowering therapy (LLT) in chronic kidney disease (CKD) results
      in a reduction in atherosclerotic cardiovascular events but not mortality. The
      risk reduction for patients on dialysis appears to be less than in pre-dialysis
      CKD. These findings may be due to the higher rate of non-atherosclerotic
      cardiovascular disease found in end-stage disease. Because of this, the role of
      LLT is less clear in CKD than in the general population. This review outlines the
      results of recent trials of LLT, particularly Ezetimibe, and implications for
      patients with CKD. The evidence in favour of lipid lowering in CKD comes largely
      from the SHARP study. This study used combined simvastatin and Ezetimibe to
      reduce cholesterol. Though the benefits of statins are well proven, there is no
      evidence that Ezetimibe independently reduces cardiovascular events in any
      population. Data which support the use of Ezetimibe show only that it effectively
      reduces cholesterol. Surrogate end-point data are contentious. Some studies
      suggest benefit whilst others suggest off-target effects that question the
      validity of Ezetimibe in the absence of quality cardiovascular outcome data.

PMID- 22613703
TI  - Whose Lyme is it anyway? Subject positions and the construction of responsibility
      for managing the health risks from Lyme disease.
AB  - There has been a significant increase during the last decade in the UK of the
      incidence of the Lyme disease. It is transmitted through tick bites, and can have
      serious health consequences if not treated early. This study examined how the
      responsibility for managing and communicating the health risks from Lyme disease
      to forest workers and recreational visitors was constructed and acted upon by 21
      interviewees in key managerial positions within one of the largest UK forestry
      organisations. The in-depth, semi-structured interviews were analysed using
      discourse analysis within a Foucauldian framework. The results demonstrated that
      the construction of responsibility towards the workforce and visitors was
      embedded into broader representations of the forest as a working, recreational
      and natural environment, as well as into the binary conceptualisation of forest
      hazards as natural and human-made. These constructions prescribed respective
      subject positions which differentially informed assumptions of responsibility,
      and consequent actions, towards the workforce and the public.

PMID- 22613702
TI  - High resolution micro arthrography of hard and soft tissues in a murine model.
AB  - OBJECTIVE: Recent developments on high resolution micro computed tomography
      (MUCT) allow imaging of soft tissues in small animal joints. Nevertheless, MUCT
      images cannot distinguish soft tissues from synovial fluid due to their similar
      mass density, limiting the 3D assessment of soft tissues volume and thickness.
      This study aimed to evaluate a lead chromate contrast agent for MUCTau
      arthrography of rat knee joints ex vivo. DESIGN: Intact tibiofemoral rat joints
      were injected with the contrast agent at different concentrations and imaged
      using a MUCT at 2.7 MUm isotropic voxel size. Cartilage thickness was measured
      using an automated procedure, validated against histological measurements, and
      analyzed as a function of MUCT image resolution. Changes in hard and soft tissues
      were also analyzed in tibiofemoral joints 4 weeks after surgical destabilization
      of the medial meniscus (DMM). RESULTS: The contrast agent diffused well
      throughout the whole knee cavity without penetrating the tissues, therefore
      providing high contrast at the boundaries between soft tissues and synovial fluid
      space. Thickness analysis of cartilage demonstrated a high similarity between
      histology and MU-arthrography approaches (R(2) = 0.90). Four weeks after surgical
      DMM, the development of osteophytes (Oph) and cartilage ulcerations was
      recognizable with MUCT, as well as a slight increase in trabecular bone porosity,
      and decrease in trabecular thickness. CONCLUSIONS: A lead chromate-based contrast
      agent allowed discriminating the synovial fluid from soft tissues of intact knee
      joints, and thus made possible both qualitative and quantitative assessment of
      hard and soft tissues in both intact and DMM tibiofemoral joints using high
      resolution MUCT.

PMID- 22613704
TI  - Active allies: hormones, stem cells and the niche in adult mammopoiesis.
AB  - Adult stem cells are recruited in response to specific physiological demands to
      regenerate, repair or maintain essential cellular components of tissues, while
      preserving self-renewal capacity. Signals that activate adult stem cells are not
      simply cell autonomous and stem cells are part of a larger dynamic framework, the
      stem cell 'niche', which integrates systemic and local cues to sustain stem cell
      functionality. The mammary stem cell niche responds readily to hormonal stimuli,
      generating pertinent signals that activate stem cells, culminating in stem cell
      expansion and tissue growth. We review here current knowledge of the mammary stem
      cell niche with attention to the potent stimulation rendered by ovarian hormones,
      relevant cellular and molecular players, and the implication of a deregulated
      niche, for breast cancer risk.

PMID- 22613705
TI  - Women's childbirth preferences and practices in the United States.
AB  - Over the past two decades, research on childbirth worldwide has documented
      women's varied perceptions of and decision-making regarding childbirth. Scholars
      have demonstrated the impact of medical authority, religion, perception of risk,
      and access to care providers on the decisions women make about where to have
      their babies and with whom. Virtually all research on how women make these
      choices, however, has focused outside the United States. To address this gap in
      the literature, we analyze data collected during 2004-2010 through 135 in-depth
      interviews with women in the U.S. who have had hospital births, homebirths with
      midwives, and homebirths without professional assistance to explore the factors
      that led them to the births they had. We supplement these interview data with
      archival analysis of birth stories and ethnographic data to offer additional
      insight into women's birth experiences. In our analysis, we utilize Pierre
      Bourdieu's concepts of "habitus" and "field" to examine the ways women's
      preferences emerge and how a sense of risk and safety shape their decision-making
      around pregnancy and parturition. Our findings indicate that while women's birth
      preferences initially emerge from their habitus, their birth practices are
      ultimately shaped by broader structural forces, particularly economic position
      and the availability of birth options.

PMID- 22613706
TI  - Decreased Mrp2 transport in severe macrovesicular fatty liver grafts.
AB  - BACKGROUND: Severe macrosteatotic liver has been regarded as a donor
      contraindication for liver transplantation. However, it has not yet been
      determined whether hepatocytes lose function before cold ischemia. This study was
      designed to elucidate certain pathophysiological alterations and how to
      ameliorate such hepatic dysfunctions. MATERIALS AND METHODS: Wistar rats were fed
      with a choline-deficient diet (CD) for up to 6 wk, and their livers were then
      perfused with Krebs-Henseleit buffer to examine bile output and biliary
      constituents. Organic anion transport from hepatocellular canalicular membranes
      through Mrp2 was examined by kinetic analyses for biliary exclusion of 5
      carboxyfluorescein (CF), a fluoroprobe excreted through Mrp2. RESULTS:
      Macrovesicular fatty deposits exceeded 60% and serum aspartate aminotransferase
      (AST) increased on 6-wk CD (CD6w), but not 3-wk CD (CD3w). Mrp2-deficient rat
      livers (Eisai hyperbilirubinemia) with 3-wk CD were more vulnerable than CD3w
      livers. In CD6w rats, bile flow rate and biliary glutathione significantly
      decreased. These declines coincided with the intracellular localization of Mrp2.
      Moreover, kinetic analyses for biliary CF revealed significant delay in 6-wk CD
      fed rat livers. Pioglitazone, a ligand of PPARgamma activating protein kinase A
      (PKA), significantly attenuated this delay by sorting Mrp2 into bile canalicular
      membranes. However, a PKA inhibitor blunted the increase in CF exclusion, re
      localizing Mrp2 into the hepatocellular cytoplasm. A thromboxane A2 synthase
      inhibitor also ameliorated the CF exclusion delay. CONCLUSION: Pioglitazone
      activated PKA, increasing Mrp2 transports to detoxify xenobiotics. Pioglitazone
      may allow the donor indications for liver transplantation to be expanded to
      include severe macrovesicular fatty livers.

PMID- 22613707
TI  - Testosterone rapidly increases ejaculate volume and sperm density in
      competitively breeding goldfish through an estrogenic membrane receptor
      mechanism.
AB  - The social environment can have dramatic influences on reproductive behavior and
      physiology in many vertebrate species. In males, interactions with conspecifics
      affect physiological processes that increase an individual's ability to compete
      for mates. For example, in some species, males rapidly adjust the number of sperm
      they ejaculate in response to sociosexual cues from male and female conspecifics,
      however, little is known about the physiological mechanisms mediating this
      behavior. In goldfish, as in many vertebrates, social cues also drive transient
      surges of the gonadal hormone testosterone (T), which induces rapid effects on
      cellular processes via its conversion to estradiol (E2). We asked whether such
      surges rapidly influence ejaculate quantity and quality by experimentally
      manipulating peripheral levels of T and E2. We show that male goldfish injected
      with T increased ejaculate (milt) volume and sperm density within just 1 hr.
      Furthermore, increases in expressible milt were dependent on the conversion of T
      to E2 by the enzyme aromatase, required activation of estrogen receptors alpha
      and beta, and were also elicited by BSA-conjugated E2, which acts on cell
      membrane-bound estrogen receptors. Together, these findings represent a novel
      steroid mechanism for the social modulation of sperm output over the short time
      scales that characterize reproductive encounters, and thus demonstrate a
      previously undescribed functional consequence of rapid estrogen signaling
      mechanisms. We suggest that such mechanisms may play a critical role in the
      enhancement of physiological and behavioral processes that increase reproductive
      success in competitive mating contexts.

PMID- 22613708
TI  - Testosterone elevation and response to gonadotropin-releasing hormone challenge
      by male northern cardinals (Cardinalis cardinalis) following aggressive behavior.
AB  - There is much discrepancy about the relationship between testosterone (T) and
      male aggressive behavior. For example, in birds, males of many species
      significantly elevate T levels during inter-male conflict. However, this is not
      universal, and in species where males typically do not elevate T during
      aggressive interactions, concentrations of the hormone are often assumed to be
      circulating at maximum levels. We examined if male northern cardinals (Cardinalis
      cardinalis) significantly elevated T during simulated territorial intrusions
      (STIs). We also examined if individuals had the capacity to further elevate T
      levels in response to gonadotropin-releasing hormone (GnRH) injections
      immediately after an aggressive encounter. Our results indicate that male
      cardinals do not significantly elevate T levels in response to STIs, but have the
      physiological capacity to significantly elevate T in response to GnRH injections
      following aggressive interactions. This implies that T levels of individuals
      captured during STIs were not at maximum concentrations. However, additional
      findings in this study also suggest the possibility that prolonged social
      instability could elicit significant elevations in T in males of this species,
      warranting further investigation.

PMID- 22613709
TI  - Adrenergic regulation of HCN4 channel requires protein association with beta2
      adrenergic receptor.
AB  - beta(1)- and beta(2)-adrenergic receptors utilize different signaling mechanisms
      to control cardiac function. Recent studies demonstrated that beta(2)-adrenergic
      receptors (beta(2)ARs) colocalize with some ion channels that are critical for
      proper cardiac function. Here, we demonstrate that beta(2)ARs form protein
      complexes with the pacemaker HCN4 channel, as well as with other subtypes of HCN
      channels. The adrenergic receptor-binding site was identified at a proximal
      region of the N-terminal tail of the HCN4 channel. A synthetic peptide derived
      from the beta(2)AR-binding domain of the HCN4 channel disrupted interaction
      between HCN4 and beta(2)AR. In addition, treatment with this peptide prevented
      adrenergic augmentation of pacemaker currents and spontaneous contraction rates
      but did not affect adrenergic regulation of voltage-gated calcium currents. These
      results suggest that the ion channel-receptor complex is a critical mechanism in
      ion channel regulation.

PMID- 22613710
TI  - Integrin alphaIIbbeta3 inside-out activation: an in situ conformational analysis
      reveals a new mechanism.
AB  - Integrins are a family of heterodimeric adhesion receptors that transmit signals
      bi-directionally across the plasma membranes. The transmembrane domain (TM) of
      integrin plays a critical role in mediating transition of the receptor from the
      default inactive to the active state on the cell surfaces. In this study, we
      successfully applied the substituted cysteine scanning accessibility method to
      determine the intracellular border of the integrin alpha(IIb)beta(3) TM in the
      inactive and active states in living cells. We examined the aqueous accessibility
      of 75 substituted cysteines comprising the C terminus of both alpha(IIb) and
      beta(3) TMs, the intracellular membrane-proximal regions, and the whole
      cytoplasmic tails, to the labeling of a membrane-permeable, cysteine-specific
      chemical biotin maleimide (BM). The active state of integrin alpha(IIb)beta(3)
      heterodimer was generated by co-expression of activating partners with the
      cysteine-substituted constructs. Our data revealed that, in the inactive state,
      the intracellular lipid/aqueous border of alpha(IIb) TM was at Lys(994) and
      beta(3) TM was at Phe(727) respectively; in the active state, the border of
      alpha(IIb) TM shifted to Pro(998), whereas the border of beta(3) TM remained
      unchanged, suggesting that complex conformational changes occurred in the TMs
      upon alpha(IIb)beta(3) inside-out activation. On the basis of the results, we
      propose a new inside-out activation mechanism for integrin alpha(IIb)beta(3) and
      by inference, all of the integrins in their native cellular environment.

PMID- 22613711
TI  - The Notch pathway attenuates interleukin 1beta (IL1beta)-mediated induction of
      adenylyl cyclase 8 (AC8) expression during vascular smooth muscle cell (VSMC)
      trans-differentiation.
AB  - Vascular smooth muscle cell (VSMC) trans-differentiation, or their switch from a
      contractile/quiescent to a secretory/inflammatory/migratory state, is known to
      play an important role in pathological vascular remodeling including
      atherosclerosis and postangioplasty restenosis. Several reports have established
      the Notch pathway as tightly regulating VSMC response to various stress factors
      through growth, migration, apoptosis, and de-differentiation. More recently, we
      showed that alterations of the Notch pathway also govern VSMC acquisition of the
      inflammatory state, one of the major events accelerating atherosclerosis. We also
      evidenced that the inflammatory context of atherosclerosis triggers a de novo
      expression of adenylyl cyclase isoform 8 (AC8), associated with the properties
      developed by trans-differentiated VSMCs. As an initial approach to understanding
      the regulation of AC8 expression, we examined the role of the Notch pathway. Here
      we show that inhibiting the Notch pathway enhances the effect of IL1beta on AC8
      expression, amplifies its deleterious effects on the VSMC trans-differentiated
      phenotype, and decreases Notch target genes Hrt1 and Hrt3. Conversely, Notch
      activation resulted in blocking AC8 expression and up-regulated Hrt1 and Hrt3
      expression. Furthermore, overexpressing Hrt1 and Hrt3 significantly decreased
      IL1beta-induced AC8 expression. In agreement with these in vitro findings, the in
      vivo rat carotid balloon-injury model of restenosis evidenced that AC8 de novo
      expression coincided with down-regulation of the Notch3 pathway. These results,
      demonstrating that the Notch pathway attenuates IL1beta-mediated AC8 up
      regulation in trans-differentiated VSMCs, suggest that AC8 expression, besides
      being induced by the proinflammatory cytokine IL1beta, is also dependent on down
      regulation of the Notch pathway occurring in an inflammatory context.

PMID- 22613712
TI  - Pin1 protein regulates Smad protein signaling and pulmonary fibrosis.
AB  - Interstitial pulmonary fibrosis is caused by the excess production of
      extracellular matrix (ECM) by Fb in response to TGF-beta1. Here, we show that the
      peptidyl-prolyl isomerase Pin1 modulates the production of many pro- and
      antifibrogenic cytokines and ECM. After acute, bleomycin injury, Pin1(-/-) mice
      showed reduced, pulmonary expression of collagens, tissue inhibitors of
      metalloproteinases, and fibrogenic cytokines but increased matrix
      metalloproteinases, compared with WT mice, despite similar levels of
      inflammation. In primary fibroblasts, Pin1 was required for TGF-beta-induced
      phosphorylation, nuclear translocation, and transcriptional activity of Smad3. In
      Pin1(-/-) cells, inhibitory Smad6 was found in the cytoplasm rather than nucleus.
      Smad6 knockdown in Pin1(-/-) fibroblasts restored TGF-beta-induced Smad3
      activation, translocation, and target gene expression. Therefore, Pin1 is
      essential for normal Smad6 function and ECM production in response to injury or
      TGF-beta and thus may be an attractive therapeutic target to prevent excess
      scarring in diverse lung diseases.

PMID- 22613713
TI  - Oxidatively modified low density lipoprotein (LDL) inhibits TLR2 and TLR4
      cytokine responses in human monocytes but not in macrophages.
AB  - Inflammation characterized by the expression and release of cytokines and
      chemokines is implicated in the development and progression of atherosclerosis.
      Oxidatively modified low density lipoproteins, central to the formation of
      atherosclerotic plaques, have been reported to signal through Toll-like receptors
      (TLRs), TLR4 and TLR2, in concert with scavenger receptors to regulate the
      inflammatory microenvironment in atherosclerosis. This study evaluates the role
      of low density lipoproteins (LDL) and oxidatively modified LDL (oxmLDL) in the
      expression and release of proinflammatory mediators IkappaBzeta, IL-6, IL-1beta,
      TNFalpha, and IL-8 in human monocytes and macrophages. Although standard LDL
      preparations induced IkappaBzeta along with IL-6 and IL-8 production, this
      inflammatory effect was eliminated when LDL was isolated under endotoxin
      restricted conditions. However, when added with TLR4 and TLR2 ligands, this low
      endotoxin preparation of oxmLDL suppressed the expression and release of IL
      1beta, IL-6, and TNFalpha but surprisingly spared IL-8 production. The
      suppressive effect of oxmLDL was specific to monocytes as it did not inhibit LPS
      induced proinflammatory cytokines in human macrophages. Thus, TLR ligand
      contamination of LDL/oxmLDL preparations can complicate interpretations of
      inflammatory responses to these modified lipoproteins. In contrast to providing a
      proinflammatory function, oxmLDL suppresses the expression and release of
      selected proinflammatory mediators.

PMID- 22613714
TI  - The pleckstrin homology (PH) domain of the Arf exchange factor Brag2 is an
      allosteric binding site.
AB  - Brag2, a Sec7 domain (sec7d)-containing guanine nucleotide exchange factor,
      regulates cell adhesion and tumor cell invasion. Brag2 catalyzes nucleotide
      exchange, converting Arf.GDP to Arf.GTP. Brag2 contains a pleckstrin homology
      (PH) domain, and its nucleotide exchange activity is stimulated by
      phosphatidylinositol 4,5-bisphosphate (PIP(2)). Here we determined kinetic
      parameters for Brag2 and examined the basis for regulation by phosphoinositides.
      Using myristoylated Arf1.GDP as a substrate, the k(cat) was 1.8 +/- 0.1/s as
      determined by single turnover kinetics, and the K(m) was 0.20 +/- 0.07 MUm as
      determined by substrate saturation kinetics. PIP(2) decreased the K(m) and
      increased the k(cat) of the reaction. The effect of PIP(2) required the PH domain
      of Brag2 and the N terminus of Arf and was largely independent of Arf
      myristoylation. Structural analysis indicated that the linker between the sec7d
      and the PH domain in Brag2 may directly contact Arf. In support, we found that a
      Brag2 fragment containing the sec7d and the linker was more active than sec7d
      alone. We conclude that Brag2 is allosterically regulated by PIP(2) binding to
      the PH domain and that activity depends on the interdomain linker. Thus, the PH
      domain and the interdomain linker of Brag2 may be targets for selectively
      regulating the activity of Brag2.

PMID- 22613715
TI  - gamma-Aminobutyric acid type B (GABAB) receptor expression is needed for
      inhibition of N-type (Cav2.2) calcium channels by analgesic alpha-conotoxins.
AB  - alpha-Conotoxins Vc1.1 and RgIA are small peptides isolated from the venom of
      marine cone snails. They have effective anti-nociceptive actions in rat models of
      neuropathic pain. Pharmacological studies in rodent dorsal root ganglion (DRG)
      show their analgesic effect is mediated by inhibition of N-type (Ca(v)2.2)
      calcium channels via a pathway involving gamma-aminobutyric acid type B (GABA(B))
      receptor. However, there is no direct demonstration that functional GABA(B)
      receptors are needed for inhibition of the Ca(v)2.2 channel by analgesic alpha
      conotoxins. This study examined the effect of the GABA(B) agonist baclofen and
      alpha-conotoxins Vc1.1 and RgIA on calcium channel currents after transient
      knockdown of the GABA(B) receptor using RNA interference. Isolated rat DRG
      neurons were transfected with small interfering RNAs (siRNA) targeting GABA(B)
      subunits R1 and R2. Efficient knockdown of GABA(B) receptor expression at mRNA
      and protein levels was confirmed by quantitative real time PCR (qRT-PCR) and
      immunocytochemical analysis, respectively. Whole-cell patch clamp recordings
      conducted 2-4 days after transfection showed that inhibition of N-type calcium
      channels in response to baclofen, Vc1.1 and RgIA was significantly reduced in
      GABA(B) receptor knockdown DRG neurons. In contrast, neurons transfected with a
      scrambled nontargeting siRNA were indistinguishable from untransfected neurons.
      In the HEK 293 cell heterologous expression system, Vc1.1 and RgIA inhibition of
      Ca(v)2.2 channels needed functional expression of both human GABA(B) receptor
      subunits. Together, these results confirm that GABA(B) receptors must be
      activated for the modulation of N-type (Ca(v)2.2) calcium channels by analgesic
      alpha-conotoxins Vc1.1 and RgIA.

PMID- 22613716
TI  - The melanosomal protein PMEL17 as a target for antibody drug conjugate therapy in
      melanoma.
AB  - Melanocytes uniquely express specialized genes required for pigment formation,
      some of which are maintained following their transformation to melanoma. Here we
      exploit this property to selectively target melanoma with an antibody drug
      conjugate (ADC) specific to PMEL17, the product of the SILV pigment-forming gene.
      We describe new PMEL17 antibodies that detect the endogenous protein. These
      antibodies help define the secretory fate of PMEL17 and demonstrate its utility
      as an ADC target. Although newly synthesized PMEL17 is ultimately routed to the
      melanosome, we find substantial amounts accessible to our antibodies at the cell
      surface that undergo internalization and routing to a LAMP1-enriched, lysosome
      related organelle. Accordingly, an ADC reactive with PMEL17 exhibits target
      dependent tumor cell killing in vitro and in vivo.

PMID- 22613717
TI  - Heterozygous carriage of a dysfunctional Toll-like receptor 9 allele affects CpG
      oligonucleotide responses in B cells.
AB  - Toll-like receptors (TLR) are employed by the innate immune system to detect
      microbial pathogens based on conserved microbial pathogen molecules. For example,
      TLR9 is a receptor for CpG-containing microbial DNA, and its activation results
      in the production of cytokines and type I interferons from human B cells and
      plasmacytoid dendritic cells, respectively. Both are required for mounting an
      efficient antibacterial or antiviral immune response. These effects are mimicked
      by synthetic CpG oligodeoxynucleotides (ODN). Although several hyporesponsive
      TLR9 variants have been reported, their functional relevance in human primary
      cells has not been addressed. Here we report a novel TLR9 allele, R892W, which is
      hyporesponsive to CpG ODN and acts as a dominant-negative in a cellular model
      system. The R892W variant is characterized by increased MyD88 binding and
      defective co-localization with CpG ODN. Whereas primary plasmacytoid dendritic
      cells isolated from a heterozygous R892W carrier responded normally to CpG by
      interferon-alpha production, carrier B cells showed impaired IL-6 and IL-10
      production. This suggests that heterozygous carriage of a hyporesponsive TLR9
      allele is not associated with complete loss of TLR9 function but that TLR9
      signals elicited in different cell types are regulated differently in human
      primary cells.

PMID- 22613719
TI  - Generation of induced pluripotent stem cells from human renal proximal tubular
      cells with only two transcription factors, OCT4 and SOX2.
AB  - The tubular epithelium of the kidney is susceptible to injury from a number of
      different causes, including inflammatory and immune disorders, oxidative stress,
      and nephrotoxins, among others. Primary renal epithelial cells remain one of the
      few tools for studying the biochemical and physiological characteristics of the
      renal tubular system. Nevertheless, differentiated primary cells are not suitable
      for recapitulation of disease properties that might arise during embryonic kidney
      formation and further maturation. Thus, cellular systems resembling kidney
      characteristics are in urgent need to model disease as well as to establish
      reliable drug-testing platforms. Induced pluripotent stem cells (iPSCs) bear the
      capacity to differentiate into every cell lineage comprising the adult organism.
      Thus, iPSCs bring the possibility for recapitulating embryonic development by
      directed differentiation into specific lineages. iPSC differentiation ultimately
      allows for both disease modeling in vitro and the production of cellular products
      with potential for regenerative medicine. Here, we describe the rapid,
      reproducible, and highly efficient generation of iPSCs derived from endogenous
      kidney tubular renal epithelial cells with only two transcriptional factors, OCT4
      and SOX2. Kidney-derived iPSCs may provide a reliable cellular platform for the
      development of kidney differentiation protocols allowing drug discovery studies
      and the study of kidney pathology.

PMID- 22613718
TI  - Evidence that formation of vimentin mitogen-activated protein kinase (MAPK)
      complex mediates mast cell activation following FcepsilonRI/CC chemokine receptor
      1 cross-talk.
AB  - Accumulating evidence points to cross-talk between FcepsilonRI and CC chemokine
      receptor (CCR)-mediated signaling pathways in mast cells. Here, we propose that
      vimentin, a protein comprising type III intermediate filament, participates in
      such cross-talk for CCL2/monocyte chemotactic protein 1 (MCP-1) production in
      mast cells, which is a mechanism for allergic inflammation. Co-stimulation via
      FcepsilonRI, using IgE/antigen, and CCR1, using recombinant CCL3/macrophage
      inflammatory protein-1alpha (MIP-1alpha), increased expression of phosphorylated,
      disassembled, and soluble vimentin in rat basophilic leukemia (RBL)-2H3 cells
      expressing human CCR1 (RBL-CCR1 cells) and bone marrow-derived murine mast cells,
      both models of mucosal type mast cells. Furthermore, co-stimulation enhanced
      production of CCL2 as well as phosphorylation of MAPK. Treating the cells with
      p38 MAPK inhibitor SB203580, but not with MEK inhibitor PD98058, reduced CCL2
      production, suggesting that p38 MAPK, but not ERK1/2, plays a critical role in
      the chemokine production. Immunoprecipitation analysis showed that vimentin
      interacts with phosphorylated ERK1/2 and p38 MAPKs in the co-simulated cells.
      Preventing disassembly of the vimentin by aggregating vimentin filaments using
      beta,beta'-iminodipropionitrile reduced the interaction of vimentin with
      phosphorylated MAPKs as well as CCL2 production in the cells. Taken together,
      disassembled vimentin interacting with phosphorylated p38 MAPK could mediate CCL2
      production in mast cells upon FcepsilonRI and CCR1 activation.

PMID- 22613720
TI  - Melittin modulates keratinocyte function through P2 receptor-dependent ADAM
      activation.
AB  - Melittin, the major component of the bee venom, is an amphipathic, cationic
      peptide with a wide spectrum of biological properties that is being considered as
      an anti-inflammatory and anti-cancer agent. It modulates multiple cellular
      functions but the underlying mechanisms are not clearly understood. Here, we
      report that melittin activates disintegrin-like metalloproteases (ADAMs) and that
      downstream events likely contribute to the biological effects evoked by the
      peptide. Melittin stimulated the proteolysis of ADAM10 and ADAM17 substrates in
      human neutrophil granulocytes, endothelial cells and murine fibroblasts. In human
      HaCaT keratinocytes, melittin induced shedding of the adhesion molecule E
      cadherin and release of TGF-alpha, which was accompanied by transactivation of
      the EGF receptor and ERK1/2 phosphorylation. This was followed by functional
      consequences such as increased keratinocyte proliferation and enhanced cell
      migration. Evidence is provided that ATP release and activation of purinergic P2
      receptors are involved in melittin-induced ADAM activation. E-cadherin shedding
      and EGFR phosphorylation were dose-dependently reduced in the presence of ATPases
      or P2 receptor antagonists. The involvement of P2 receptors was underscored in
      experiments with HEK cells, which lack the P2X7 receptor and showed strikingly
      increased response to melittin stimulation after transfection with this receptor.
      Our study provides new insight into the mechanism of melittin function which
      should be of interest particularly in the context of its potential use as an anti
      inflammatory or anti-cancer agent.

PMID- 22613721
TI  - A venom-derived neurotoxin, CsTx-1, from the spider Cupiennius salei exhibits
      cytolytic activities.
AB  - CsTx-1, the main neurotoxic acting peptide in the venom of the spider Cupiennius
      salei, is composed of 74 amino acid residues, exhibits an inhibitory cysteine
      knot motif, and is further characterized by its highly cationic charged C
      terminus. Venom gland cDNA library analysis predicted a prepropeptide structure
      for CsTx-1 precursor. In the presence of trifluoroethanol, CsTx-1 and the long C
      terminal part alone (CT1-long; Gly-45-Lys-74) exhibit an alpha-helical structure,
      as determined by CD measurements. CsTx-1 and CT1-long are insecticidal toward
      Drosophila flies and destroys Escherichia coli SBS 363 cells. CsTx-1 causes a
      stable and irreversible depolarization of insect larvae muscle cells and frog
      neuromuscular preparations, which seem to be receptor-independent. Furthermore,
      this membranolytic activity could be measured for Xenopus oocytes, in which CsTx
      1 and CT1-long increase ion permeability non-specifically. These results support
      our assumption that the membranolytic activities of CsTx-1 are caused by its C
      terminal tail, CT1-long. Together, CsTx-1 exhibits two different functions; as a
      neurotoxin it inhibits L-type Ca(2+) channels, and as a membranolytic peptide it
      destroys a variety of prokaryotic and eukaryotic cell membranes. Such a dualism
      is discussed as an important new mechanism for the evolution of spider venomous
      peptides.

PMID- 22613722
TI  - Monoubiquitination promotes calpain cleavage of the protein phosphatase 2A (PP2A)
      regulatory subunit alpha4, altering PP2A stability and microtubule-associated
      protein phosphorylation.
AB  - Multiple neurodegenerative disorders are linked to aberrant phosphorylation of
      microtubule-associated proteins (MAPs). Protein phosphatase 2A (PP2A) is the
      major MAP phosphatase; however, little is known about its regulation at
      microtubules. alpha4 binds the PP2A catalytic subunit (PP2Ac) and the microtubule
      associated E3 ubiquitin ligase MID1, and through unknown mechanisms can both
      reduce and enhance PP2Ac stability. We show MID1-dependent monoubiquitination of
      alpha4 triggers calpain-mediated cleavage and switches alpha4's activity from
      protective to destructive, resulting in increased Tau phosphorylation. This
      regulatory mechanism appears important in MAP-dependent pathologies as levels of
      cleaved alpha4 are decreased in Opitz syndrome and increased in Alzheimer
      disease, disorders characterized by MAP hypophosphorylation and
      hyperphosphorylation, respectively. These findings indicate that regulated inter
      domain cleavage controls the dual functions of alpha4, and dysregulation of
      alpha4 cleavage may contribute to Opitz syndrome and Alzheimer disease.

PMID- 22613723
TI  - Transcription factors ER71/ETV2 and SOX9 participate in a positive feedback loop
      in fetal and adult mouse testis.
AB  - ER71, also known as ETV2, is an ETS transcription factor that is expressed during
      embryogenesis and in adult testes. We show that Er71 transcription can be up
      regulated by SRY, the key determinant of male differentiation. Accordingly, SRY
      bound to and activated the Er71 promoter, and mutation of a putative SRY binding
      site abolished this promoter activation. In turn, ER71 was able to bind to the
      promoter of Sox9, the primary target of SRY and a critical transcription factor
      for maintenance of the Sertoli cell phenotype. Mutation of the ER71 binding site
      in the Sox9 promoter suppressed ER71-dependent up-regulation of Sox9
      transcription, and a dominant-negative ER71 molecule severely reduced Sox9
      transcription in a Sertoli cell line. Conversely, SOX9 bound the Er71 promoter in
      vivo and Sox9 down-regulation reduced Er71 transcript levels. Together, these
      data suggest a mechanism by which SRY induces Sox9 and Er71 transcription early
      in testis differentiation, whereas ER71 and SOX9 participate in an autoregulatory
      loop to sustain each other's expression after Sry expression has subsided in
      mice. Thereby, ER71 and SOX9 may affect late testis development as well as the
      function of the adult male gonad.

PMID- 22613724
TI  - Azemiopsin from Azemiops feae viper venom, a novel polypeptide ligand of
      nicotinic acetylcholine receptor.
AB  - Azemiopsin, a novel polypeptide, was isolated from the Azemiops feae viper venom
      by combination of gel filtration and reverse-phase HPLC. Its amino acid sequence
      (DNWWPKPPHQGPRPPRPRPKP) was determined by means of Edman degradation and mass
      spectrometry. It consists of 21 residues and, unlike similar venom isolates, does
      not contain cysteine residues. According to circular dichroism measurements, this
      peptide adopts a beta-structure. Peptide synthesis was used to verify the
      determined sequence and to prepare peptide in sufficient amounts to study its
      biological activity. Azemiopsin efficiently competed with alpha-bungarotoxin for
      binding to Torpedo nicotinic acetylcholine receptor (nAChR) (IC(50) 0.18 +/- 0.03
      MUm) and with lower efficiency to human alpha7 nAChR (IC(50) 22 +/- 2 MUm). It
      dose-dependently blocked acetylcholine-induced currents in Xenopus oocytes
      heterologously expressing human muscle-type nAChR and was more potent against the
      adult form (alpha1beta1epsilondelta) than the fetal form (alpha1beta1gammadelta),
      EC(50) being 0.44 +/- 0.1 MUm and 1.56 +/- 0.37 MUm, respectively. The peptide
      had no effect on GABA(A) (alpha1beta3gamma2 or alpha2beta3gamma2) receptors at a
      concentration up to 100 MUm or on 5-HT(3) receptors at a concentration up to 10
      MUm. Ala scanning showed that amino acid residues at positions 3-6, 8-11, and 13
      14 are essential for binding to Torpedo nAChR. In biological activity azemiopsin
      resembles waglerin, a disulfide-containing peptide from the Tropidechis wagleri
      venom, shares with it a homologous C-terminal hexapeptide, but is the first
      natural toxin that blocks nAChRs and does not possess disulfide bridges.

PMID- 22613725
TI  - Dissecting mannose 6-phosphate-insulin-like growth factor 2 receptor complexes
      that control activation and uptake of plasminogen in cells.
AB  - The plasminogen (Plg) activation cascade on the cell surface plays a central role
      in cell migration and is involved in a plethora of physiological and pathological
      processes. Its regulation is coordinated by many receptors, in particular the
      urokinase-type plasminogen activator receptor (uPAR, CD87), receptors that
      physically interact and functionally cooperate with uPAR, and Plg binding
      molecules. Here we studied the impact of one of the Plg binding molecules, the
      mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P-IGF2R, CD222), on
      cellular Plg activation. By developing both in vitro and in vivo Plg activation
      assays on size-fractionated lysates of M6P-IGF2R-silenced cells, we identified
      Plg-associated complexes with M6P-IGF2R as the regulatory factor. Using lipid
      raft preserving versus dissolving detergents, we found lipid dependence of the
      Plg regulatory function of these complexes. Furthermore, M6P-IGF2R-silencing in
      uPAR-positive human cell lines reduced internalization of Plg, resulting in
      elevated Plg activation. In contrast, the expression of human M6P-IGF2R in mouse
      embryonic fibroblasts derived from M6P-IGF2R knock-out mice enhanced Plg
      internalization. Finally, peptide 18-36 derived from the Plg-binding site within
      M6P-IGF2R enhanced Plg uptake. Thus, by targeting Plg to endocytic pathways, M6P
      IGF2R appears to control Plg activation within cells that might be important to
      restrict plasmin activity to specific sites and substrates.

PMID- 22613726
TI  - Cytoskeletal modulation of lipid interactions regulates Lck kinase activity.
AB  - The actin cytoskeleton promotes clustering of proteins associated with
      cholesterol-dependent rafts, but its effect on lipid interactions that form and
      maintain rafts is not understood. We addressed this question by determining the
      effect of disrupting the cytoskeleton on co-clustering of dihexadecyl-(C(16))
      anchored DiO and DiI, which co-enrich in ordered lipid environments such as
      rafts. Co-clustering was assayed by fluorescence resonance energy transfer (FRET)
      in labeled T cells, where rafts function in the phosphoregulation of the Src
      family kinase Lck. Our results show that probe co-clustering was sensitive to
      depolymerization of actin filaments with latrunculin B (Lat B), inhibition of
      myosin II with blebbistatin, and treatment with neomycin to sequester
      phosphatidylinositol 4,5-bisphosphate. Cytoskeletal effects on lipid interactions
      were not restricted to order-preferring label because co-clustering of C(16)
      anchored DiO with didodecyl (C(12))-anchored DiI, which favors disordered lipids,
      was also reduced by Lat B and blebbistatin. Furthermore, conditions that
      disrupted probe co-clustering resulted in activation of Lck. These data show that
      the cytoskeleton globally modulates lipid interactions in the plasma membrane,
      and this property maintains rafts that function in Lck regulation.

PMID- 22613728
TI  - A novel metabolic pathway for glucose production mediated by alpha-glucosidase
      catalyzed conversion of 1,5-anhydrofructose.
AB  - alpha-Glucosidase is in the glycoside hydrolase family 13 (13AG) and 31 (31AG).
      Only 31AGs can hydrate the D-glucal double bond to form alpha-2-deoxyglucose.
      Because 1,5-anhydrofructose (AF), having a 2-OH group, mimics the oxocarbenium
      ion transition state, AF may be a substrate for alpha-glucosidases. alpha
      Glucosidase-catalyzed hydration produced alpha-glucose from AF, which plateaued
      with time. Combined reaction with alpha-1,4-glucan lyase and 13AG eliminated the
      plateau. Aspergillus niger alpha-glucosidase (31AG), which is stable in organic
      solvent, produced ethyl alpha-glucoside from AF in 80% ethanol. The findings
      indicate that alpha-glucosidases catalyze trans-addition. This is the first
      report of alpha-glucosidase-associated glucose formation from AF, possibly
      contributing to the salvage pathway of unutilized AF.

PMID- 22613729
TI  - Caesium-137 and strontium-90 temporal series in the Tagus River: experimental
      results and a modelling study.
AB  - The objective of this work consisted of analysing the spatial and temporal
      evolution of two radionuclide concentrations in the Tagus River. Time-series
      analysis techniques and numerical modelling have been used in this study. (137)Cs
      and (90)Sr concentrations have been measured from 1994 to 1999 at several
      sampling points in Spain and Portugal. These radionuclides have been introduced
      into the river by the liquid releases from several nuclear power plants in Spain,
      as well as from global fallout. Time-series analysis techniques have allowed the
      determination of radionuclide transit times along the river, and have also
      pointed out the existence of temporal cycles of radionuclide concentrations at
      some sampling points, which are attributed to water management in the reservoirs
      placed along the Tagus River. A stochastic dispersion model, in which transport
      with water, radioactive decay and water-sediment interactions are solved through
      Monte Carlo methods, has been developed. Model results are, in general, in
      reasonable agreement with measurements. The model has finally been applied to the
      calculation of mean ages of radioactive content in water and sediments in each
      reservoir. This kind of model can be a very useful tool to support the decision
      making process after an eventual emergency situation.

PMID- 22613727
TI  - Calpain induces N-terminal truncation of beta-catenin in normal murine liver
      development: diagnostic implications in hepatoblastomas.
AB  - Hepatic competence, specification, and liver bud expansion during development
      depend on precise temporal modulation of the Wnt/beta-catenin signaling. Also,
      loss- and gain-of-function studies have revealed pleiotropic roles of beta
      catenin in proliferation and hepatocyte and biliary epithelial cell
      differentiation, but precise mechanisms remain unknown. Here we utilize livers
      from different stages of murine development to determine beta-catenin signaling
      and downstream targets. Although during early liver development full-length beta
      catenin is the predominant form, at late stages, where full-length beta-catenin
      localizes to developing biliary epithelial cells only, a 75-kDa truncated beta
      catenin species is the principal form localizing at the membrane and in the
      nucleus of differentiating hepatocytes. The truncated species lacks 95 N-terminal
      amino acids and is transcriptionally active. Our evidence points to proteolytic
      cleavage of beta-catenin by calpain as the mechanism of truncation in cell-free
      and cell-based assays. Intraperitoneal injection of a short term calpain
      inhibitor to timed pregnant female mice abrogated beta-catenin truncation in the
      embryonic livers. RNA-seq revealed a unique set of targets transcribed in cells
      expressing truncated versus full-length beta-catenin, consistent with different
      functionalities. A further investigation using N- and C-terminal-specific beta
      catenin antibodies on human hepatoblastomas revealed a correlation between full
      length versus truncated beta-catenin and differentiation status, with embryonal
      hepatoblastomas expressing full-length beta-catenin and fetal hepatoblastomas
      expressing beta-catenin lacking its N terminus. Thus we conclude that calpain
      mediated cleavage of beta-catenin plays a role in regulating hepatoblast
      differentiation in mouse and human liver, and the presence of the beta-catenin N
      terminus correlates with differentiation status in hepatoblastomas.

PMID- 22613730
TI  - Cocaine-induced c-Fos expression in rats selectively bred for high or low
      saccharin intake and in rats selected for high or low impulsivity.
AB  - Sweet preference and impulsivity are predictors of cocaine self-administration;
      however, no research has been conducted to investigate neuronal activation in key
      brain reward areas after first time exposure to cocaine in rats that differ in
      their propensity for cocaine-seeking and -taking behavior. In this study we used
      rats that had been selectively bred for high vs. low saccharin intake and rats
      selected for high vs. low impulsivity for food. The goal of this study was to
      investigate whether there are differences of c-Fos reactivity between high and
      low phenotypes and determine whether these differences are similar between the
      two animal models. A group of rats was bred for high or low saccharin intake.
      Another group of rats was selected as high or low impulsive based on performance
      in a delay-discounting task. Subsequently, rats were given an acute injection of
      cocaine or saline and then c-Fos expression was observed and analyzed in several
      brain regions. The low reward-seeking phenotypes showed higher cocaine-induced c
      Fos expression in several of these regions. Low saccharin preferring rats showed
      higher cocaine-induced c-Fos expression in the nucleus accumbens shell, and low
      impulsive rats showed higher cocaine-induced c-Fos expression in the
      orbitofrontal cortex and cingulate gyrus 1 area. In addition, both low impulsive
      and low saccharin rats had higher cocaine-induced c-Fos in the dorsal medial and
      dorsal lateral caudate putamen. The results indicate that individual differences
      in neuronal reactivity exist prior to chronic exposure to drugs of abuse.
      Furthermore, similar differences between the two animal models may be indicative
      of a common mechanism underlying vulnerability to drugs of abuse.

PMID- 22613731
TI  - The selective neuropeptide Y Y5 agonist [cPP(1-7),NPY(19
      23),Ala31,Aib32,Gln34]hPP differently modulates emotional processes and body
      weight in the rat.
AB  - The neuropeptide Y (NPY) has been suggested to act as a major regulator of
      emotional processes and body weight. The full spectrum of biological effects of
      this peptide is mediated by at least four classes of receptors known as the Y(1),
      Y(2), Y(4), and Y(5) subtypes. However, the respective contribution of each of
      these receptor subtypes, especially the Y(5) subtype, in emotional processes is
      still mostly unknown. In the present study, we investigated the effect of long
      term administration of a selective Y(5) agonist [cPP(1-7),NPY(19
      23),Ala(31),Aib(32),Gln(34)]hPP on emotional processes and body weight using two
      rat models of emotional dysfunctions, the corticosterone (CORT)-induced anxiety
      model as well as the olfactory bulbectomized (OBX) model of depression and
      anxiety in Wistar and Sprague-Dawley rats, respectively. The sub-chronic
      administration of the Y(5) agonist reversed the high levels of locomotion,
      rearing and grooming in the open field test and the impaired social activity
      induced by OBX, while increased the percentage of entries and time in the open
      arm of the elevated plus maze in CORT-treated rats. Furthermore, this Y(5)
      agonist increased body weight in both strains of control rats. These data further
      demonstrate that Y(5) receptors are not only involved in the control of body
      weight but also mediate emotional processing under challenged conditions. Thus,
      the pharmacotherapeutic administration of a Y(5) agonist could be considered as a
      potentially novel strategy to alleviate some forms of anxiety and depression in
      humans.

PMID- 22613734
TI  - Parosteal osteosarcoma mimicking osteochondroma: A radio-histologic approach on
      two cases.
AB  - BACKGROUND: Parosteal osteosarcoma is a well-differentiated variant of
      osteosarcoma that affects the surface of the bone. The imaging pattern is very
      typical. We report two cases mimicking an osteochondroma, radiologically and
      histologically and propose an explanation. METHODS: The review of 86 parosteal
      osteosarcomas of bone revealed this atypical pattern only once. A consultation
      case was received in the same time, and added to ours. Patients were 28 years old
      and 56 years old females. Imaging studies included two radiographs, two CTscans,
      one MRI examination and one bone scan and the results were compared to histology.
      RESULTS: On imaging, both lesions presented as ossified lobulated masses attached
      with a broad base to the underlying cortex. No radiolucent cleft separated the
      masses and the host bone and cortex continuity between the mass and the femur was
      seen, with medullary communication. The marrow of the mass had a different
      density and intensity compared to normal marrow. So, there were features of an
      osteochondroma (cortex and medullary continuity) and of a parosteal osteosarcoma
      (ossified marrow). Pathological assessment on the final specimen confirmed the
      presence of low-grade parosteal osteosarcomas, after an erroneous diagnosis of
      osteochondroma on the initial biopsy. CONCLUSIONS: Parosteal osteosarcoma can be
      rarely confused with osteochondroma. A radiologic-pathologic correlation is
      essential. Cortex continuity is the most misleading imaging feature that may
      occur in parosteal osteosarcomas. A knowledge of this misleading pattern will
      help diagnose the lesion from the beginning.

PMID- 22613732
TI  - Microglial inhibitory factor (MIF/TKP) mitigates secondary damage following
      spinal cord injury.
AB  - Spinal cord injury (SCI) induces an immune response during which microglia, the
      resident immunocompetent cells of the central nervous system, become activated
      and migrate to the site of damage. Depending on their state of activation,
      microglia secrete neurotoxic or neurotrophic factors that influence the
      surrounding environment and have a detrimental or restorative effect following
      SCI, including causing or protecting bystander damage to nearby undamaged tissue.
      Subsequent infiltration of macrophages contributes to the SCI outcome. We show
      here that suppressing microglia/macrophage activation using the tripeptide
      macrophage/microglia inhibitory factor (MIF/TKP) reduced secondary injury around
      the lesion epicenter in the murine dorsal hemisection model of SCI; it decreased
      the hypertrophic change of astrocytes and caused an increase in the number of
      axons present within the lesion epicenter. Moreover, timely inhibition of
      microglial/macrophage activation prevented demyelination and axonal dieback by
      modulating oligodendrocyte survival and oligodendrocyte precursor maturation.
      Microglia/macrophages located within or proximal to the lesion produced
      neurotoxic factors, such as tumor necrosis factor alpha (TNF-alpha). These
      results suggest that microglia/macrophages within the epicenter at early time
      points post injury are neurotoxic, contributing to demyelination and axonal
      degeneration and that MIF/TKP could be used in combination with other therapies
      to promote functional recovery.

PMID- 22613735
TI  - Crustacean-borne infections with microphallid metacercariae (Digenea:
      Microphallidae) from focal areas in Meghalaya, north-east India.
AB  - During a survey of edible Crustacea for recovery of infective stages
      (metacercariae) of potential helminthozoonoses of trematode origin in north-east
      India, the crab species Barytelphusa lugubris mansoniana, collected from
      suspected foci of lungfluke infection in Meghalaya and Assam, was found to
      harbour metacercarial cysts that were different from the earlier reported
      infection, in which the lungfluke Paragonimus was confirmed to be implicated.
      Using morphological criteria, this metacercaria was identified as Microphallus
      indicus Mukherjee & Ghosh, 1967 of the trematode family Microphallidae. The
      present study extends the previous work by providing molecular characterization
      of this parasite using ribosomal internal transcribed spacer regions (rDNA ITS1
      and ITS2) and the partial large ribosomal subunit DNA, lsr. These target regions
      were amplified by polymerase chain reaction (PCR) using trematode universal
      primers and sequenced. In BLAST analysis the query sequences were found close to
      members of Microphallidae and closest to the genus Microphallus.

PMID- 22613733
TI  - Novel classes of non-coding RNAs and cancer.
AB  - For the many years, the central dogma of molecular biology has been that RNA
      functions mainly as an informational intermediate between a DNA sequence and its
      encoded protein. But one of the great surprises of modern biology was the
      discovery that protein-coding genes represent less than 2% of the total genome
      sequence, and subsequently the fact that at least 90% of the human genome is
      actively transcribed. Thus, the human transcriptome was found to be more complex
      than a collection of protein-coding genes and their splice variants. Although
      initially argued to be spurious transcriptional noise or accumulated evolutionary
      debris arising from the early assembly of genes and/or the insertion of mobile
      genetic elements, recent evidence suggests that the non-coding RNAs (ncRNAs) may
      play major biological roles in cellular development, physiology and pathologies.
      NcRNAs could be grouped into two major classes based on the transcript size;
      small ncRNAs and long ncRNAs. Each of these classes can be further divided,
      whereas novel subclasses are still being discovered and characterized. Although,
      in the last years, small ncRNAs called microRNAs were studied most frequently
      with more than ten thousand hits at PubMed database, recently, evidence has begun
      to accumulate describing the molecular mechanisms by which a wide range of novel
      RNA species function, providing insight into their functional roles in cellular
      biology and in human disease. In this review, we summarize newly discovered
      classes of ncRNAs, and highlight their functioning in cancer biology and
      potential usage as biomarkers or therapeutic targets.

PMID- 22613736
TI  - Cholecystokinin knock-down in the basolateral amygdala has anxiolytic and
      antidepressant-like effects in mice.
AB  - Cholecystokinin (CCK) is a neuropeptide widely distributed in the mammalian
      brain. This peptide regulates many physiological functions and behaviors, such as
      cardio-respiratory control, thermoregulation, nociception, feeding, memory
      processes and motivational responses, and plays a prominent role in emotional
      responses including anxiety and depression. CCK-expressing brain regions involved
      in these functions remain unclear and their identification represents an
      important step towards understanding CCK function in the brain. The basolateral
      amygdala (BLA) is strongly involved in emotional processing and expresses high
      levels of CCK. In this study we examined the contribution of CCK expressed in
      this brain region to emotional responses in mice. To knockdown CCK specifically
      in the BLA, we used stereotaxic delivery of recombinant adeno-associated viral
      vectors expressing a CCK-targeted shRNA. This procedure efficiently reduced CCK
      levels locally. shCCK-treated animals showed reduced levels of anxiety in the
      elevated plus-maze, and lower despair-like behavior in the forced swim test. Our
      data demonstrate that CCK expressed in the BLA represents a key brain substrate
      for anxiogenic and depressant effects of the peptide. The study also suggests
      that elevated amygdalar CCK could contribute to panic and major depressive
      disorders that have been associated with CCK dysfunction in humans.

PMID- 22613738
TI  - Menorrhagia and rash in a female adolescent.

PMID- 22613737
TI  - Rapamycin down-regulates KCC2 expression and increases seizure susceptibility to
      convulsants in immature rats.
AB  - Seizure susceptibility to neurological insults, including chemical convulsants,
      is age-dependent and most likely reflective of overall differences in brain
      excitability. The molecular and cellular mechanisms underlying development
      dependent seizure susceptibility remain to be fully understood. Because the
      mammalian target of rapamycin (mTOR) pathway regulates neurite outgrowth,
      synaptic plasticity and cell survival, thereby influencing brain development, we
      tested if exposure of the immature brain to the mTOR inhibitor rapamycin changes
      seizure susceptibility to neurological insults. We found that inhibition of mTOR
      by rapamycin in immature rats (3-4 weeks old) increases the severity of seizures
      induced by pilocarpine, including lengthening the total seizure duration and
      reducing the latency to the onset of seizures. Rapamycin also reduces the minimal
      dose of pentylenetetrazol (PTZ) necessary to induce clonic seizures. However, in
      mature rats, rapamycin does not significantly change the seizure sensitivity to
      pilocarpine and PTZ. Likewise, kainate sensitivity was not significantly affected
      by rapamycin treatment in either mature or immature rats. Additionally, rapamycin
      treatment down-regulates the expression of potassium-chloride cotransporter 2
      (KCC2) in the thalamus and to a lesser degree in the hippocampus. Pharmacological
      inhibition of thalamic mTOR or KCC2 increases susceptibility to pilocarpine
      induced seizure in immature rats. Thus, our study suggests a role for the mTOR
      pathway in age-dependent seizure susceptibility.

PMID- 22613739
TI  - Comparison of blood pressure and sympathetic activity of rabbits in their home
      cage and the laboratory environment.
AB  - Methodological improvements in measuring cardiovascular parameters have meant
      that data can be collected from freely moving animals in their home cage.
      However, experiments in rabbits still often require them to be restrained in a
      laboratory setting. The aim of this study was to determine whether measurements
      collected when rabbits were placed in a holding box in the laboratory are
      representative of values obtained in freely moving conscious rabbits. Nine New
      Zealand White rabbits received two radiotelemetry implants to monitor mean
      arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). The MAP
      measured in the laboratory (71 +/- 1 mmHg) was similar to that in the home cage
      (69 +/- 1 mmHg), but there was less MAP variability. The RSNA was also similar in
      both environments. In contrast, laboratory heart rate (HR) was 7% lower than home
      cage HR (181 +/- 4 beats min(-1), P < 0.001), but HR variability was similar.
      Baroreflex gain, assessed by spectral analysis, was 19% higher in the laboratory
      than in the home cage due to lower MAP mid-frequency variability in the
      laboratory. Home cage circadian patterns of MAP and HR were strongly influenced
      by feeding and activity. Nevertheless, MAP and RSNA laboratory measurements were
      the same as average 24 h values and remained similar over several weeks. We
      conclude that while HR is generally lower in the laboratory, a valid
      representation of MAP and RSNA can be given by laboratory measurements.

PMID- 22613740
TI  - Altered cortical activation patterns associated with baroreflex unloading
      following 24 h of physical deconditioning.
AB  - Cardiovascular arousal is associated with patterned cortical activity changes.
      Head-down-tilt bed rest (HDBR) dimishes the baroreflex-mediated cardiac control.
      The present study tested the hypothesis that HDBR deconditioning would modify the
      forebrain organization for heart rate (HR) control during baroreflex unloading.
      Heart rate variability (HRV), blood pressure and plasma hormones were analysed at
      rest, whereas HR and cortical autonomic activation patterns (functional magnetic
      resonance imaging) were measured during graded and randomly assigned lower body
      negative pressure treatments (LBNP, -15 and -35 mmHg) both before (Pre) and after
      (Post) a 24 h HDBR protocol (study 1; n = 8). An additional group was tested
      before and following diuretic-induced hypovolaemia (study 2; n = 9;
      spironolactone, 100 mg day(-1) for 3 days) that mimicked the plasma volume lost
      during HDBR (-15% in both studies; P < 0.05). Head-down bed rest with
      hypovolaemia did not affect baseline HR, mean arterial pressure, HRV or plasma
      catecholamines. Head-down bed rest augmented the LBNP-induced HR response (P <
      0.05), and this was associated with bed-rest-induced development of the following
      changes: (i) enhanced activation within the genual anterior cingulate cortex and
      the right anterior insular cortex; and (ii) deactivation patterns within the
      subgenual regions of the anterior cingulate cortex. Diuretic treatment (without
      HDBR) did not affect baseline HR and mean arterial pressure, but did reduce
      resting HRV and elevated circulating noradrenaline and plasma renin activity (P <
      0.05). The greater HR response to LBNP following diuretic (P < 0.05) was
      associated with diminished activation of the right anterior insula. Our findings
      indicate that 24 h of HDBR minimized the impact of diuretic treatment on baseline
      autonomic and cardiovascular variables. The findings also indicate that despite
      the similar augmentation of HR responses to LBNP and despite similar pre
      intervention cortical activation patterns, HDBR and diuretic treatment produced
      different effects on the cortical responses, with HDBR affecting anterior
      cingulate cortex and right insula regions, whereas diuretic treatment affected
      primarily the right insula alone, but in a direction that was opposite to HDBR.
      The data indicate that physical deconditioning can induce rapid functional
      changes within the cortical circuitry associated with baroreflex unloading,
      changes that are distinct from diuretic-induced hypovolaemia. The results suggest
      that physical activity patterns exert a rapid and notable impact on the cortical
      circuitry associated with cardiovascular control.

PMID- 22613741
TI  - Control of breathing and blood pressure by parafacial neurons in conscious rats.
AB  - The retrotrapezoid nucleus (RTN), located in the parafacial region, contains
      glutamatergic neurons that express the transcriptor factor Phox2b and that are
      suggested to be central respiratory chemoreceptors. Studies in anaesthetized
      animals or in vitro have suggested that RTN neurons are important in the control
      of breathing by influencing respiratory rate, inspiratory amplitude and active
      expiration. However, the contribution of these neurons to cardiorespiratory
      control in conscious rats is not clear. Male Holtzman rats (280-300 g, n = 6-8)
      with bilateral stainless-steel cannulae implanted into the RTN were used. In
      conscious rats, the microinjection of the ionotropic glutamatergic agonist NMDA
      (5 pmol in 50 nl) into the RTN increased respiratory frequency (by 42%), tidal
      volume (by 21%), ventilation (by 68%), peak expiratory flow (by 24%) and mean
      arterial pressure (MAP, increased by 16 +/- 4, versus saline, 3 +/- 2 mmHg).
      Bilateral inhibition of the RTN neurons with the GABA(A) agonist muscimol (100
      pmol in 50 nl) reduced resting ventilation (52 +/- 34, versus saline, 250 +/- 56
      ml min(-1) kg(-1) with absolute values) and attenuated the respiratory response
      to hypercapnia and hypoxia. Muscimol injected into the RTN slightly reduced
      resting MAP (decreased by 13 +/- 7, versus saline, increased by 3 +/- 2 mmHg),
      without changing the effects of hypercapnia or hypoxia on MAP and heart rate. The
      results suggest that RTN neurons activate facilitatory mechanisms important to
      the control of ventilation in resting, hypoxic or hypercapnic conditions in
      conscious rats.

PMID- 22613742
TI  - Effect of exercise on mouse liver and brain bioenergetic infrastructures.
AB  - To assess the effects of exercise on liver and brain bioenergetic
      infrastructures, we exposed C57BL/6 mice to 6 weeks of moderate-intensity
      treadmill exercise. During the training period, fasting blood glucose was lower
      in exercised mice than in sedentary mice, but serum insulin levels were not
      reduced. At week 6, trained mice showed a paradoxical decrease in plasma lactate
      during exercise, which was accompanied by an increase in the liver
      monocarboxylate transporter 2 protein level (~30%, P < 0.05). Exercise increased
      liver peroxisomal proliferator-activated receptor-gamma coactivator 1alpha
      expression (approximately twofold, P < 0.001), NAD-dependent deacetylase sirtuin
      1 protein (~30%, P < 0.05), p38 protein (~15%, P < 0.05), cytochrome c oxidase
      subunit 4 isoform 1 protein (~50%, P < 0.05) and AMP-activated protein kinase
      phosphorylation (~40%, P < 0.05). Despite this, liver mitochondrial DNA copy
      number (~30%, P = 0.05), mitochondrial transcription factor A expression (~15%, P
      < 0.05), cytochrome c oxidase subunit 2 expression (~10%, P < 0.05), cAMP
      response element binding protein phosphorylation (~60%, P < 0.05) and brain
      derived neurotrophic factor expression (~40%, P < 0.05) were all reduced, while
      cytochrome oxidase and citrate synthase activities were unchanged. The only
      altered brain parameter observed was a reduction in tumour necrosis factor alpha
      expression (~35%, P < 0.05); tumour necrosis factor alpha expression was
      unchanged in liver. Our data suggest that lactate produced by exercising muscle
      modifies the liver bioenergetic infrastructure, and enhanced liver uptake may in
      turn limit the ability of exercise-generated lactate to modify brain
      bioenergetics. Also, it appears that, at least in the liver, a dissociated
      mitochondrial biogenesis, in which some components are strategically enhanced
      while others are minimized, can occur.

PMID- 22613743
TI  - Influence of menstrual cycle phase on muscle metaboreflex control of cardiac
      baroreflex sensitivity, heart rate and blood pressure in humans.
AB  - We sought to determine whether menstrual cycle phase influences muscle
      metaboreflex control of spontaneous cardiac baroreflex sensitivity (cBRS), blood
      pressure (BP) and heart rate (HR). Twenty-three young women not taking oral
      contraceptives were studied during the early (EF; low oestrogen, low
      progesterone) and late follicular menstrual phases (LF; high oestrogen, low
      progesterone). Protocol 1 consisted of leg cycling at low (21 +/- 2 W) and
      moderate workloads (71 +/- 3 W) in free-flow conditions and with partial flow
      restriction (bilateral thigh-cuff inflation at 100 mmHg) to activate the muscle
      metaboreflex. Protocol 2 consisted of rhythmic hand-grip exercise with
      incremental upper arm-cuff inflation (0, 80, 100 and 120 mmHg) to elicit graded
      metaboreflex activation. Both protocols were followed by post-exercise ischaemia.
      Leg cycling decreased cBRS (EF, 20 +/- 5, 6 +/- 1 and 1 +/- 0.1 ms mmHg(-1); and
      LF, 19 +/- 3, 6 +/- 0.4, 1 +/- 0.1 ms mmHg(-1) during rest, low- and moderate
      intensity leg cycling, respectively) and increased HR in an intensity-dependent
      manner, while BP remained unchanged. Partial flow restriction during leg cycling
      decreased cBRS, and increased HR and BP. During post-exercise ischaemia, HR and
      BP remained elevated, while cBRS remained suppressed (EF, 4.2 +/- 0.6 ms mmHg(
      1); and LF, 4.7 +/- 0.5 ms mmHg(-1); P < 0.05 versus rest). Cardiac baroreflex
      sensitivity was unchanged during hand-grip with and without partial flow
      restriction and post-exercise ischaemia. No differences in cBRS, HR or BP
      responses were observed between EF and LF at any time during either protocol.
      These data indicate that endogenous fluctuations in oestrogen between the EF and
      LF phases of the menstrual cycle do not influence muscle metaboreflex control of
      cBRS, BP or HR in young women.

PMID- 22613744
TI  - Automated measurement of nerve fiber density using line intensity scan analysis.
AB  - Quantification of nerve fibers in peripheral and central nervous systems is
      important for the understanding of neuronal function, organization and
      pathological changes. However, current methods to quantify nerve fibers are
      resource-intensive and often provide an indirect measurement of nerve fiber
      density. Here, we describe an automated and efficient method for nerve fiber
      quantification, which we developed by making use of widely available software and
      analytical techniques, including Hessian-based feature extraction in NIH ImageJ
      and line intensity scan analysis. The combined use of these analytical tools
      through an automated routine enables reliable detection and quantification of
      nerve fibers from low magnification, non-uniformly labeled epifluorescence
      images. This allows for time-efficient determination of nerve density and also
      comparative analysis in large brain structures, such as hippocampus or between
      various regions of neural circuitry. Using this method, we have obtained accurate
      measurements of cholinergic fiber density in hippocampus and a large area of
      cortex in mouse brain sections immunolabeled with an antibody against the
      vesicular acetylcholine transporter (VAChT). The density values are comparable
      among animals tested, showing a high degree of reproducibility. Because our
      method can be performed at relatively low cost and in large tissue sections where
      nerve fibers can be labeled by various antibodies or visualized by expression of
      reporter proteins, such as green fluorescent protein in transgenic mice, we
      expect our method to be broadly useful in both research and clinical
      investigation. To our knowledge, this is the first method to reliably quantify
      nerve fibers through a rapid and automated protocol.

PMID- 22613745
TI  - Incretin therapy and its effect on body weight in patients with diabetes.
AB  - Glucagon-like peptide 1 (GLP-1) analogues and dipeptidyl peptidase-4 (DPP-4)
      inhibitors are two classes of treatments for type 2 diabetes, which enhance the
      well-known 'incretin effect' of increased insulin secretion in response to food
      intake. This concise review introduces both types of incretin-based therapies and
      focuses on the extra-pancreatic effect of GLP-1 on body weight. As well as
      improving glycaemic control in subjects with type 2 diabetes, these treatments
      have the additional benefits of improving weight management in these patients,
      with GLP-1 receptor agonists causing weight loss and DPP-4 inhibitors being
      weight neutral.

PMID- 22613746
TI  - Variation in supermarket exposure to energy-dense snack foods by socio-economic
      position.
AB  - OBJECTIVE: The present study aimed to examine the availability of energy
      dense,nutrient-poor snack foods (and fruits and vegetables) in supermarkets
      located insocio-economically advantaged and disadvantaged neighbourhoods. DESIGN:
      Cross-sectional supermarket audit. SETTING: Melbourne, Australia. Measures
      included product shelf space and number of varieties for soft drinks, crisps,
      chocolate, confectionery and fruits and vegetables, as well as store size.
      SUBJECTS: Thirty-five supermarkets (response 83 %) from neighbourhoods in the
      lowest and highest quintile of socio-economic disadvantage. RESULTS: Shelf space
      allocated to soft drinks (23?6m v. 17?7m, P50?006), crisps (16?5m v. 13?0m,
      P50?016), chocolate (12?2m v. 10?1m, P50?022) and confectionery (6?7m v. 5?1m,
      P50?003) was greater in stores from socioeconomically disadvantaged
      neighbourhoods. After adjustment for store size (stores in disadvantaged areas
      being larger), shelf space for confectionery (6?3m v. 5?6m, P50?024) and combined
      shelf space for all energy-dense foods and drinks (55?0m v. 48?9m, P50?017)
      remained greater in stores from socio-economically disadvantaged neighbourhoods.
      The ratio of shelf space allocated to fruits and vegetables to that for energy
      dense snack foods also varied by socio-economic disadvantage after adjustment for
      store size (most disadvantaged v. least disadvantaged: 1?7 v. 2?1, P50?025).
      Varieties of fruits and vegetables and chocolate bars were more numerous in less
      disadvantaged areas (P,0?05). CONCLUSIONS: Exposure to energy-dense snack foods
      and soft drinks in supermarketswas greater in socio-economically disadvantaged
      neighbourhoods. Thismay impact purchasing, consumption and cultural norms related
      to eatingbehaviours and may therefore work against elimination of the known
      socioeconomicgradient in obesity levels. Reform of supermarket stocking
      practicesmay represent an effective means of obesity prevention.

PMID- 22613747
TI  - Increased risk of sexual dysfunction in male patients with psoriasis: a
      nationwide population-based follow-up study.
AB  - INTRODUCTION: An association between psoriasis and sexual dysfunction (SD) has
      been explored. However, the risk of SD after the diagnosis of psoriasis relative
      to the age-matched general population remains unknown. Aim.  To clarify the risk
      of developing SD in male patients with psoriasis. METHODS: From 2000 to 2001, we
      identified 12,300 male patients with newly diagnosed psoriasis and 61,500
      matching controls from National Health Insurance Database in Taiwan. MAIN OUTCOME
      MEASURES: The two cohorts were followed up until 2008, and we observed the
      occurrence of SD by registry of SD diagnosis in the database. Stratified Cox
      proportional hazard regressions were used to calculate the 7-year SD risk for
      these two groups. RESULTS: Of the 73,800 sampled patients, 1,812 patients (2.46%)
      experienced SD during the 7-year follow-up period, including 373 (3.03% of
      patients with psoriasis) in the study group and 1,439 (2.34% of patients without
      psoriasis) in the comparison group. The hazard ratio (HR) for SD for patients
      with psoriasis was 1.27 times (95% confidence interval [CI], 1.11-1.46; P =
      0.001) as high as that for patients without psoriasis after adjusting for age,
      monthly income, number of health-care visits, systemic treatment, and other
      comorbidities. Stratified analysis showed that the risk of SD was higher in
      patients older than 60 years old (HR: 1.42, 95% CI: 1.12-1.81) and patients with
      psoriatic arthritis (HR: 1.78, 95% CI: 1.08-2.91). However, the risk of SD was
      not significantly elevated in patients receiving systemic treatment, including
      retinoid, methotrexate, and cyclosporine. CONCLUSIONS: Male patients with
      psoriasis are at increased risk of developing SD. Physicians should pay attention
      to the impact of psoriasis on psychosocial and sexual health, especially in old
      aged patients.

PMID- 22613748
TI  - Introducing the International Journal of Nursing Knowledge.

PMID- 22613749
TI  - Perception: a concept analysis.
AB  - PURPOSE: Concept analysis methodology by Walker and Avant (2005) was used to
      define, describe, and delimit the concept of perception. DATA SOURCE: Nursing
      literature in the Medline database was searched for definitions of "perception."
      DATA SYNTHESIS: Definitions, uses, and defining attributes of perception were
      identified; model and contrary cases were developed; and antecedents,
      consequences, and empirical referents were determined. CONCLUSIONS: An
      operational definition for the concept was developed. IMPLICATIONS FOR NURSING
      PRACTICE: Nurses need to be cognizant of how perceptual differences impact the
      delivery of nursing care. In research, a mixed methodology approach may yield a
      richer description of the phenomenon and provide useful information for clinical
      practice.

PMID- 22613750
TI  - A nursing conceptual model for contamination.
AB  - PURPOSE: To propose a nursing model of contamination that describes the key
      features of contamination at a level of abstraction needed for clinical decision
      making. DATA SOURCES: Relevant literature on contamination, biopreparedness, and
      classic epidemiologic literature were reviewed and analyzed. DATA SYNTHESIS: A
      model of contamination was created along with a description of benefits of use in
      practice, education, and research. DISCUSSION: The nursing profession is called
      to respond to contamination incidents on a local, national, and global level.
      Achieving optimum health outcomes while managing contamination incidents is
      enhanced by nurses' use of a model that incorporates six elements to identify and
      name instances of contamination and select suitable outcomes and interventions.

PMID- 22613751
TI  - Implementation and evaluation of the nursing process in primary health care.
AB  - PURPOSE: The purpose of this study is to publicize the experience of implementing
      and developing the nursing process in a sanitary area of primary health care
      (PHC), and to assess the outcomes reached during the past 9 years. METHODS: This
      descriptive longitudinal study was carried out in the 42 PHC centers in the 11th
      Primary Care Area of Madrid, Spain. FINDINGS: Between 2001 and 2009, 243,838 new
      nursing diagnoses were performed. The indicator of resolution capacity ranged
      from 75% to 80% for the attended problems. CONCLUSIONS: Nurses in the 11th PHC
      Area have effectively incorporated the nursing process as a work methodology in
      their caregiving practices. IMPLICATIONS FOR NURSING PRACTICE: The nursing
      process can be used to identify nursing care issues and assess the capacity for
      resolution.

PMID- 22613752
TI  - How nurse practitioners make decisions regarding coronary heart disease risk: a
      social judgment analysis.
AB  - PURPOSE: Understanding how nurse practitioners use clinical decision skills in
      practice has the potential to guide education programs to ensure safe, competent,
      and high quality advanced nursing practice. This study used the lens of social
      judgment theory to examine the clinical decision making of 60 nurse
      practitioners. METHODS: A three-group pretest-posttest comparison design was used
      to evaluate how much insight nurse practitioners had into their clinical decision
      making process. FINDINGS: Nurse practitioners had modest insight into their
      clinical decision-making process. CONCLUSION: Self-insight has implications for
      enhancing nurses' decision making, improving education, and fostering agreement
      among advanced practice nurses. IMPLICATIONS FOR NURSING PRACTICE: Self-insight
      has implications for developing professional decision making and promoting
      appropriate educational opportunities for advanced practice nurses.

PMID- 22613753
TI  - Case study: a young male with auditory hallucinations in paranoid schizophrenia.
AB  - PURPOSE: The purpose of this case study is to demonstrate use of the nursing
      process and the standardized nursing languages of NANDA International (NANDA-I),
      the Nursing Outcomes Classification (NOC), and the Nursing Interventions
      Classification (NIC) to assist a young male with paranoid schizophrenia to deal
      with auditory hallucinations. DATA SOURCES: Data were obtained from the
      experience and expertise of the author and published literature. DATA SYNTHESIS:
      This case study demonstrates nurses' clinical decision making in providing care
      for an adolescent with mental illness. CONCLUSION: This case study provides the
      pertinent nursing diagnosis, patient outcomes, and nursing interventions for a
      young male with auditory hallucinations in paranoid schizophrenia. IMPLICATIONS
      FOR NURSING: The use of NANDA-I, NOC, and NIC can provide the necessary framework
      for enhancing and improving the management of care with patients who experience
      auditory hallucinations in paranoid schizophrenia.

PMID- 22613754
TI  - Cues for nursing diagnosis of ineffective self-management of fluid and dietary
      restrictions in dialysis therapy in Japan.
AB  - PURPOSE: We aimed to identify the cues of expert nurses and validate the cue
      information on the defining characteristics for a nursing diagnosis of
      ineffective self-management of fluid and dietary restrictions in dialysis therapy
      in Japan. METHODS: We used qualitative interviews and two-round Delphi studies.
      FINDINGS: The expert nurses regarded four signs of unmaintained fluid and dietary
      restrictions as major defining characteristics and nine other cues as minor
      defining characteristics. CONCLUSIONS: Expert nurses in dialysis therapy regard
      symptoms of health behavior as major cues for nursing diagnosis of ineffective
      self-management of fluid and dietary restrictions in dialysis therapy.
      IMPLICATIONS FOR NURSING PRACTICE: Verification of the clinical validity and
      development of a specific, clinically useful database on nursing diagnoses are
      required.

PMID- 22613755
TI  - Strengths and difficulties in children with cochlear implants--comparing self
      reports with reports from parents and teachers.
AB  - OBJECTIVE: The aim was to explore and compare how children with cochlear
      implants, their parents, and their teachers perceive the children's mental health
      in terms of emotional and behavioral strengths and difficulties. METHODS: The
      self-report, parents', and teachers' versions of the Strengths and Difficulties
      Questionnaire (SDQ) were used to assess the mental health of 22 children with
      cochlear implants. The children's assessments were then compared to the parents'
      and 17 teachers' assessments. The data were analyzed using the SPSS software
      package. RESULTS: Total difficulties (p=.000), emotional symptoms (p=.000), and
      conduct problems (p=.007) were greater according to the children than according
      to parents and teachers. Younger children (9 years, n=12) reported more emotional
      symptoms than older children (12 and 15 years, n=10). Almost a quarter of the
      children rated themselves in a way indicating mental ill-health. Parents and
      teachers each indicated mental ill-health for one child. CONCLUSIONS: Children
      with cochlear implants express greater concerns about their mental health than
      their parents and teachers do. This is important knowledge for adults in
      families, schools, and health care in order to support these children and offer
      treatment when needed.

PMID- 22613756
TI  - Mutation detection in GJB2 gene among Malays with non-syndromic hearing loss.
AB  - OBJECTIVES: To identify the mutations in the GJB2 gene and to determine its
      association with non-syndromic hearing loss in Malays. METHODS: A comparative
      cross sectional study was conducted on a group of children from the deaf schools
      and the normal schools. A total of 91 buccal cell samples of non-syndromic
      hearing loss and 91 normal hearing children were taken. Polymerase chain reaction
      was used to amplify the coding region of GJB2 gene. The PCR product of GJB2
      coding region was preceded with screening for mutations using denaturing high
      performance liquid chromatography (dHPLC) and mutations detected were confirmed
      by DNA sequencing. RESULTS: Twelve sequence variations including mutations and
      polymorphisms were found in 32 patients and 37 control subjects. The variations
      were G4D, V27I, E114G, T123N, V37I and R127H in both groups, W24X, R32H, 257_259
      del CGC and M34L in patients only and I203T and V153I in control subjects only.
      There were no association between homozygous (P=0.368) or heterozygous (P=0.164)
      GJB2 gene and non-syndromic hearing loss. CONCLUSIONS: The types of GJB2 gene
      mutation were different and vary in Malay non-syndromic hearing loss as compared
      to the other races. Furthermore, the mutation did not associate with hearing loss
      in the population. Other related genes are believed to be involved and need to be
      sought in this group of patients.

PMID- 22613757
TI  - The epileptic singers of belle epoque Paris.
AB  - In late 19th century Paris, people with epilepsy were treated alongside those
      with hysteria in the now famous Salpetriere Hospital, where both conditions were
      deemed to have a neurological basis. When Jean Martin Charcot became chief
      physician at the Salpetriere Hospital in 1862, he described himself 'in
      possession of a kind of museum of living pathology whose holdings were virtually
      inexhaustible'. He opened the doors of his 'living museum' and exhibited his
      prize specimens to all of Paris. By putting his patients on display, Charcot
      introduced a vogue for pathology that permeated well beyond the world of medical
      enquiry and into the public psyche and vernacular. Not only did Charcot's
      demonstrations provide the inspiration for high culture in the form of operas,
      plays and novels, they also provided the inspiration for the 'gommeuses
      epileptiques' (epileptic singers), who entertained the masses at the cafe
      concerts. This paper explores the foundations of our current medical approaches
      to mental illness and epilepsy, with a particular focus on the boundaries that
      emerged between hysteria and epilepsy in 19th century Paris. These clinical
      boundaries were both shaped by and reflected in the popular entertainments in the
      city.

PMID- 22613758
TI  - Smoke exposure of human macrophages reduces HDAC3 activity, resulting in enhanced
      inflammatory cytokine production.
AB  - Chronic obstructive pulmonary disease (COPD) is a debilitating condition
      resulting from exposure to pollutants such as cigarette smoke. Pulmonary
      macrophages secrete a plethora of inflammatory mediators that are increased in
      the lungs of COPD patients, but whether this phenotype results directly from
      smoke exposure remains unknown. Using an in vitro model for alveolar macrophages
      (AM) derived from human peripheral blood monocytes with granulocyte-macrophage
      stimulating factor (GM-MO), we analyzed the mechanistic connection between
      cigarette smoke exposure and histone deacetylase (HDAC) regulation, hypothesized
      to be a contributing factor in COPD pathophysiology. Here we show that acute
      smoke exposure inhibits HDAC enzymatic activity in GM-MO. Analysis of mRNA and
      total cellular proteins for expression of class I (1, 2, 3 and 8), class II (4,
      5, 6, 7, 9, 10), and class IV (11) HDAC revealed no effect of smoke exposure,
      whereas nuclear HDAC3 protein content was reduced. To better understand the
      physiological significance of reduced HDAC3 activity, we utilized siRNA to
      knockdown HDAC1, 2 and 3 individually. Interestingly, siRNA-mediated reduction of
      HDAC3 resulted in increased production of IL8 and IL1beta in response to LPS
      stimulation, while HDAC2 knockdown had no effect on either cytokine. Lower
      nuclear content of HDAC3 in the context of equivalent total HDAC protein levels
      following smoke exposure may reflect increased nuclear export of HDAC3, allowing
      increased nuclear factor kappa b (NF-kappaB ) driven cytokine expression that can
      contribute to inflammation.

PMID- 22613759
TI  - Comparison of the levels of the growth factors in umbilical cord serum and human
      milk and its clinical significance.
AB  - The process of the growth of the fetus begins in the uterus and gets further
      accelerated following the birth, especially during initial few months. The role
      of the growth factors in the physiology of the cellular growth is already well
      established. Vascular endothelial growth factor (VEGF) and hepatocyte growth
      factor (HGF) seem to be imperative for angiogenesis, cell development and
      proliferation as well as maintenance of the tissues. The levels of these factors
      in the maternal serum during pregnancy as well as during postpartum period are
      insignificant. Consequently, we hypothesized that the fetus receives moderate
      supply of these growth factors from the placenta during its stay in the uterus.
      This supply gets further augmented during the postpartum period through the
      different source, i.e. mother's milk. To study this physiological transition of
      the source of the growth factors from the placenta to the breast milk, the
      concentrations of VEGF and HGF in the cord serum of full term neonates and that
      in the breast milk of the corresponding mothers were analyzed during ELISA. The
      human milk, especially the colostrum revealed significantly higher levels of VEGF
      and HGF (1541.759 +/- 119.349 pg/ml and 7129.249 +/- 273.472 pg/ml) than cord
      serum (16.632 +/- 0.773 pg/ml and 2581.6 +/- 108.275 pg/ml) respectively. The
      multifold higher levels of VEGF observed in colostrum probably correlates with
      its high neonatal requirement for the maturation of the gastrointestinal
      epithelium following birth. The higher levels of both the growth factors in the
      breast milk than those observed in the cord serum probably explain their higher
      needs by the neonates for immunological protection, protein synthesis and
      neurocognitive development. The observations of the present study strengthen the
      policy of the colostrum feeding, which is promoted by organizations like World
      Health Organization (WHO). This study further documents the fact that the
      commercial milk formulae cannot replace the human milk.

PMID- 22613760
TI  - Frontal dysfunctions of ALS-PBP patients in relation to their bulbar symptoms and
      rCBF decline.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal
      disease characterized by progressive degeneration of spinal and bulbar motor
      neurons. However up to 50% ALS patients may also have cognitive dysfunction which
      has not been fully examined. METHODS: 35 ALS patients [23 patients presenting
      with limb-type ALS (ALS-limb) and 12 patients presenting with primary bulbar
      palsy (PBP)-type ALS (ALS-PBP)] and 5 Spinal and Bulbar Muscular Atrophy (SBMA)
      patients have participated. To assess cognitive function mini-mental state
      examination (MMSE), Hasegawa dementia scale-revised (HDS-R), and frontal
      assessment battery (FAB) were performed. Additionally the time to complete card
      flipping with a computerized touch panel-type screening test was also examined.
      To investigate regional cerebral blood flow (rCBF), single-photon emission
      computed tomography (SPECT) using a (99m)Tc labeled ethyl cysteinate dimer
      ((99m)Tc-ECD) were performed. Statistical image analysis was performed using the
      easy Z-score imaging system (eZIS). RESULTS: HDS-R and FAB scores were
      significantly lower in the ALS-PBP group than in age- and gender-matched control
      subjects or ALS-limb groups (p<0.01). The time to complete card flipping was
      significantly longer in the ALS-PBP group than in the control and ALS-limb groups
      (p<0.01). Although MMSE, HDS-R and FAB scores and the time to complete card
      flipping had no correlation with ALS functional rating scale-revised (ALSFRS-R)
      or Norris-limb scale scores, FAB score (r=0.63, p <0.01) and the time to complete
      card flipping (r=-0.66, p<0.01) were strongly correlated with Norris-bulbar
      score. The eZIS showed that rCBF of the frontal lobe was more severely declined
      in ALS-PBP patients than in ALS-limb patients (p<0.05). CONCLUSION: These results
      suggest a selective decline of frontal cerebral functions in the ALS-PBP group in
      relation to their bulbar symptoms and rCBF decline.

PMID- 22613761
TI  - Single-molecule imaging on living bacterial cell surface by high-speed AFM.
AB  - Advances in microscopy have contributed to many biologic discoveries. Electron
      microscopic techniques such as cryo-electron tomography are remarkable tools for
      imaging the interiors of bacterial cells in the near-native state, whereas
      optical microscopic techniques such as fluorescence imaging are useful for
      following the dynamics of specific single molecules in living cells. Neither
      technique, however, can be used to visualize the structural dynamics of a single
      molecule at high resolution in living cells. In the present study, we used high
      speed atomic force microscopy (HS-AFM) to image the molecular dynamics of living
      bacterial cell surfaces. HS-AFM visualizes the dynamic molecular processes of
      isolated proteins at sub-molecular resolution without the need for complicated
      sample preparation. In the present study, magnetotactic bacterial cells were
      anchored in liquid medium on substrate modified by poly-L-lysine and
      glutaraldehyde. High-resolution HS-AFM images of live cell surfaces showed that
      the bacterial outer membrane was covered with a net-like structure comprising
      holes and the hole rims framing them. Furthermore, HS-AFM captured the dynamic
      movement of the surface ultrastructure, showing that the holes in the net-like
      structure slowly diffused in the cell surface. Nano-dissection revealed that
      porin trimers constitute the net-like structure. Here, we report for the first
      time the direct observation of dynamic molecular architectures on a live cell
      surface using HS-AFM.

PMID- 22613762
TI  - Structural studies on the oligomeric transition of a small heat shock protein,
      StHsp14.0.
AB  - The small heat shock proteins (sHsps), which are widely found in all domains of
      life, bind and stabilize denatured proteins to prevent aggregation. The sHsps
      exist as large oligomers that are composed of 9-40 subunits and control their
      chaperone activity by the transition of the oligomeric state. Though the
      oligomeric transition is important for the biological function of most sHsps,
      atomic details have not been elucidated. Here, we report crystal structures in
      both the 24-meric and dimeric states for an sHsp, StHsp14.0 from Sulfolobus
      tokodaii, in order to reveal changes upon the oligomeric transition. The results
      indicate that StHsp14.0 forms a spherical 24-mer with a diameter of 115 A. The
      diameter is defined by the inter-monomer angle in the dimer. The dimer structure
      in the dimeric state shows only small differences from that in the 24-meric
      state. Some significant differences are exclusively observed at the binding site
      for the C-terminus. Although a dimer has four interactive sites with neighboring
      dimers, the weakness of the respective interactions is indicated from the size
      exclusion chromatography. The small structural changes imply an activation
      mechanism mediated by multiple weak interactions.

PMID- 22613763
TI  - Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as a
      diagnostic marker of ventilator-associated pneumonia.
AB  - OBJECTIVE: To determine the utility of soluble triggering receptor expressed on
      myeloid cells-1 (sTREM-1) levels in bronchoalveolar lavage fluid (BALF) and
      exhaled breath condensate (EBC) samples from patients who underwent bronchoscopy
      for a clinical suspicion of ventilator-associated pneumonia (VAP), to categorize
      patients as VAP positive and VAP negative, when compared to quantitative culture
      results of BALF. METHODS: Observational study conducted on admitted patients in
      the trauma-surgical, medical-cardiac, burn, and neurosurgical ICUs of Harborview
      Medical Center between March 2009 and May 2010. BALF and EBC samples were
      obtained from 45 patients with clinically suspected VAP. Bronchoscopy was
      performed on the day of clinically suspected VAP. sTREM-1 levels in EBC and BAL
      fluid were measured using quantikine human TREM-1 immunoassay. VAP was diagnosed
      by quantitative cultures of BALF. RESULTS: The concentrations of sTREM-1 in BALF
      and EBC did not correlate with VAP status. sTREM-1 levels did not discriminate
      VAP positive from VAP negative patients, when compared to quantitative cultures
      of BALF as the gold standard. Using a cutoff value of 204 pg/mL for BALF sTREM-1
      levels resulted in a sensitivity of 79% and a specificity of 23%. A cutoff value
      of 10 pg/mL for EBC sTREM-1 levels resulted in a sensitivity of 42% and a
      specificity of 50%. CONCLUSIONS: EBC and BALF sTREM-1 levels did not effectively
      categorize patients as VAP positive or VAP negative when using direct
      bronchoscopic quantitative culture samples as the comparison standard.

PMID- 22613765
TI  - The APP intracellular domain (AICD) inhibits Wnt signalling and promotes neurite
      outgrowth.
AB  - beta- and gamma-secretase cleave the amyloid precursor protein (APP) to release
      the amyloidogenic beta-amyloid peptides (Abeta) and the APP intracellular domain
      (AICD). Abeta has been widely believed to initiate pathogenic cascades
      culminating in Alzheimer's disease (AD). However, the physiological functions of
      the AICD remain elusive. In this study, we found the AICD to strongly inhibit Wnt
      induced transcriptional reporter activity, and to counteract Wnt-induced c-Myc
      expression. Loss of the AICD resulted in an increased responsiveness to Wnt/beta
      catenin-mediated transcription. Mechanically, the AICD was found to interact with
      glycogen synthase kinase 3 beta (GSK3beta) and promote its kinase activity. The
      subsequent AICD-strengthened Axin-GSK3beta complex potentiates beta-catenin poly
      ubiquitination. Functional studies in N(2)a mouse neuroblastoma cells, rat
      pheochromocytoma PC12 cells and primary neurons showed that the AICD facilitated
      neurite outgrowth. And AICD antagonised Wnt3a-suppressed growth arrest and
      neurite outgrowth in N2a and PC12 cells. Taken together, our results identify the
      AICD as a novel inhibitory factor of the canonical Wnt signalling pathway and
      suggest its regulatory role in neuronal cell proliferation and differentiation.

PMID- 22613764
TI  - Mechanisms underlying the protein-kinase mediated regulation of the HERG
      potassium channel synthesis.
AB  - The HERG (human ether-a-go-go related gene) potassium channel aids in the
      repolarization of the cardiomyocyte membrane at the end of each action potential.
      We have previously shown that sustained protein kinase A or C (PKA and PKC)
      activity specifically enhances channel synthesis over the course of hours to days
      in heterologous expression and cardiac myocytes. The kinase-mediated augmentation
      of the channel is post-transcriptional and occurs near or at the endoplasmic
      reticulum. Here we report our further investigations into the mechanisms of
      kinase-mediated augmentation of HERG channel protein. We show that HERG channel
      phosphorylation alone is not sufficient for the PKA-dependent increase to occur.
      In vitro translation studies indicate that an additional factor is required for
      the process. Pharmacologic inhibitors suggest that the channel augmentation is
      not due to kinase-mediated alteration in proteasome or lysosome activity. PKA
      activation had no effect on stability of HERG mRNA and polyribosomal profiling
      showed that kinase activity did not elevate translation from low to high rates.
      Transcriptional inhibition results suggest that the additional cellular factor is
      a PKA-regulated protein. Together, these findings suggest that PKA-mediated
      augmentation of HERG abundance is more complex than previously appreciated
      involving enhancement of already active translation rates, phosphorylation of the
      channel protein and at least one other cyclic-AMP/PKA-responsive protein. Further
      exploration of molecular components of this regulatory pathway will be necessary
      to determine exact mechanism and the biomedical impact of this process in vivo.

PMID- 22613766
TI  - Detection of ubiquitin-proteasome enzymatic activities in cells: application of
      activity-based probes to inhibitor development.
AB  - BACKGROUND: Synthetic probes that mimic natural substrates can enable the
      detection of enzymatic activities in a cellular environment. One area where such
      activity-based probes have been applied is the ubiquitin-proteasome pathway,
      which is emerging as an important therapeutic target. A family of reagents has
      been developed that specifically label deubiquitylating enzymes (DUBs) and
      facilitate characterization of their inhibitors. SCOPE OF REVIEW: Here we focus
      on the application of probes for intracellular DUBs, a group of specific
      proteases involved in the ubiquitin proteasome system. In particular, the
      functional characterization of the active subunits of this family of proteases
      that specifically recognize ubiquitin and ubiquitin-like proteins will be
      discussed. In addition we present the potential and design of activity-based
      probes targeting kinases and phosphatases to study phosphorylation. MAJOR
      CONCLUSIONS: Synthetic molecular probes have increased our understanding of the
      functional role of DUBs in living cells. In addition to the detection of
      enzymatic activities of known members, activity-based probes have contributed to
      a number of functional assignments of previously uncharacterized enzymes. This
      method enables cellular validation of the specificity of small molecule DUB
      inhibitors. GENERAL SIGNIFICANCE: Molecular probes combined with mass
      spectrometry-based proteomics and cellular assays represent a powerful approach
      for discovery and functional validation, a concept that can be expanded to other
      enzyme classes. This addresses a need for more informative cell-based assays that
      are required to accelerate the drug development process. This article is part of
      a Special Issue entitled: Ubiquitin Drug Discovery and Diagnostics.

PMID- 22613767
TI  - zVAD-fmk upregulates caspase-9 cleavage and activity in etoposide-induced cell
      death of mouse embryonic fibroblasts.
AB  - Caspases are key effectors of programmed cell death. Down- and up-regulation of
      their activity are involved in different pathologies. In most cells, zVAD-fmk
      prevents apoptosis. However, unexpected effects of zVAD-fmk have been
      characterized in different laboratories, cell models and cell death processes. We
      have previously shown that zVAD-fmk accelerates p53-dependent apoptosis in rat
      embryonic fibroblasts. In this study, we pursued our investigations on zVAD-fmk
      effects and focused our study at the mitochondrial level in mouse embryonic
      fibroblasts (MEFs). In both primary and immortalized (by AgT or 3T9 protocol)
      MEFs, zVAD-fmk increased etoposide-induced loss of DeltaPsim. This increase
      correlated with an increase of the number of apoptotic cells in primary and 3T9
      MEFs, but did not in AgT MEFs. In both types of immortalized MEFs, zVAD-fmk
      regulated neither p53 levels nor transcriptional activities, suggesting that zVAD
      fmk acts downstream of p53. In MEFs, zVAD-fmk increased p53-dependent loss of
      DeltaPsim, cytochrome c release and caspase-9 activity. Indeed, zVAD-fmk
      inhibited effector caspases (caspases-3, -6, -7) as expected but increased
      caspase-9 cleavage and activity in etoposide-treated MEFs. Q-VD-OPh, another
      caspase inhibitor, also increased both loss of DeltaPsim and caspase-9 cleavage
      in etoposide-treated MEFs. Invalidation of bax and bak suppressed p53-dependent
      cell death and zVAD-fmk regulation of this process. Invalidation of caspase-9 did
      not inhibit mitochondrial membrane depolarization but suppressed zVAD-fmk
      amplification of this process. Altogether, our data suggest that caspase-9
      activity is up-regulated by zVAD-fmk and is involved in an amplification loop of
      etoposide-induced cell death at the mitochondrial level in MEFs.

PMID- 22613769
TI  - Systemic inflammation in 222.841 healthy employed smokers and nonsmokers: white
      blood cell count and relationship to spirometry.
AB  - BACKGROUND: Smoking has been linked to low-grade systemic inflammation, a known
      risk factor for disease. This state is reflected in elevated white blood cell
      (WBC) count. OBJECTIVE: We analyzed the relationship between WBC count and
      smoking in healthy men and women across several age ranges who underwent
      preventive medical check-ups in the workplace. We also analysed the relationship
      between smoking and lung function. METHODS: Cross-sectional descriptive study in
      163 459 men and 59 382 women aged between 16 and 70 years. Data analysed were
      smoking status, WBC count, and spirometry readings. RESULTS: Total WBC showed
      higher counts in both male and female smokers, around 1000 to 1300 cell/ml (t
      test, P < 0.001). Forced expiratory volume in 1 second (FEV1%) was higher in
      nonsmokers for both sexes between 25 to 54 years (t test, P < 0.001). Analysis of
      covariance showed a multiple variable effect of age, sex, smoking status, body
      mass index on WBC count. The relationship between WBC blood count and smoking
      status was confirmed after the sample was stratified for these variables. Smokers
      with airway obstruction measured by FEV1% were found to have higher WBC counts,
      in comparison to smokers with a normal FEV1% among similar age and BMI groups.
      CONCLUSIONS: Smoking increases WBC count and affects lung function. The effects
      are evident across a wide age range, underlining the importance of initiating
      preventive measures as soon as an individual begins to smoke.

PMID- 22613770
TI  - Total thyroidectomy for amiodarone-associated thyrotoxicosis: should surgery
      always be delayed for pre-operative medical preparation?
AB  - OBJECTIVE: Amiodarone can induce severe hyperthyroidism that justifies its
      withdrawal and the introduction of antithyroid drugs. Continuing amiodarone use,
      failure to control hyperthyroidism and poor clinical progress may require
      thyroidectomy. This study aimed to evaluate patients' post-operative development
      and mid-term outcome after thyroidectomy for amiodarone-associated
      thyrotoxicosis. STUDY DESIGN: Prospective case series. SETTING: Tertiary care
      centre. SUBJECTS AND METHODS: We prospectively collected cases of amiodarone
      associated thyrotoxicosis requiring thyroidectomy due to failure of antithyroid
      treatment, despite amiodarone discontinuation. Post-thyroidectomy complications
      were compared immediately, 30 days and one year post-operatively, and also for
      scheduled versus emergency surgery cases. RESULTS: Of 11 total cases, nine
      scheduled thyroidectomy cases had no morbidity after elective surgery. Two cases
      required emergency surgery for multiple organ failure and cardiac problems.
      Immediate post-operative complications (mostly haemodynamic) occurred in both
      cases (emergency vs routine surgery, p = 0.018). CONCLUSION: In such cases, pre
      operative medical treatment is vital to limit peri- and post-operative
      complications, but surgery should not be delayed if the haemodynamic status
      deteriorates. Surgery, with careful anaesthesia, is the cornerstone of the
      treatment.

PMID- 22613768
TI  - Inhibition of mycobacterial infection by the tumor suppressor PTEN.
AB  - The tumor suppressor PTEN is a lipid phosphatase that is frequently mutated in
      various human cancers. PTEN suppresses tumor cell proliferation, survival, and
      growth mainly by inhibiting the PI3K-Akt signaling pathway through
      dephosphorylation of phosphatidylinositol 3,4,5-triphosphate. In addition to it
      role in tumor suppression, the PTEN-PI3K pathway controls many cellular
      functions, some of which may be important for cellular resistance to infection.
      Currently, the intersection between tumorigenic signaling pathways and cellular
      susceptibility to infection is not well defined. In this study we report that
      PTEN signaling regulates infection of both noncancerous and cancerous cells by
      multiple intracellular mycobacterial pathogens and that pharmacological
      modulation of PTEN signaling can affect mycobacterial infection. We found that
      PTEN deficiency renders multiple types of cells hyper-susceptible to infection by
      Mycoplasma and Mycobacterium bovis Bacillus Calmette-Guerin (BCG). The lipid
      phosphatase activity of PTEN is required for attenuating infection. Furthermore,
      we found mycobacterial infection activates host cell Akt phosphorylation, and
      pharmacological inhibition of Akt or PI3K activity reduced levels of
      intracellular infection. Intriguingly, inhibition of mTOR, one of the downstream
      components of the Akt signaling and a promising cancer therapeutic target, also
      lowered intracellular Bacillus Calmette-Guerin levels in mammary epithelial
      cancer MCF-7 cells. These findings demonstrate a critical role of PTEN-regulated
      pathways in pathogen infection. The relationship of PTEN-PI3K-Akt mTOR status and
      susceptibility to mycobacterial infection suggests that the interaction of
      mycobacterial pathogens with cancer cells may be influenced by genetic
      alterations in the tumor cells.

PMID- 22613771
TI  - Imaging of hibernomas: A retrospective study on twelve cases.
AB  - BACKGROUND: To analyze the imaging features of hibernomas on computed tomography
      (CT) and magnetic resonance (MRI). METHODS: Twelve hibernomas were
      retrospectively assessed with CT and MR imaging and compared to the histology of
      the specimen RESULTS: Nine females and three males with a mean age of 30 years
      were included. Ten tumors occurred in the thigh and two affected the subcutis of
      the periscapular and buttock regions. On eight CT scans, seven (87,5%) lesions
      were homogeneous and mildly to moderately hyperdense compared to subcutaneous fat
      while one lesion was heterogeneous with mixed hypo and hyperattenuating areas. On
      six T1W images, five (83,3%) lesions appeared homogeneous and hypointense
      relative to subcutaneous fat and one was heterogeneous. Incomplete fat
      suppression was depicted in all cases. All lesions displayed marked enhancement.
      Large intratumoral vessels were depicted in three of the 12 (25%) cases.
      Septations were depicted on four of the eight unenhanced CT and on all six MRI
      examinations. CONCLUSIONS: Hibernoma usually appears hypodense and hypointense
      relative to subcutaneous fat on pre-contrast CT and MR T1W with variable
      enhancement patterns and incomplete fat suppression on STIR or fat-saturated
      sequences. These characteristics relate directly to the presence of brown fat.
      However, atypical findings such as heterogeneous patterns of mixed fatty and non
      fatty components on unenhanced CT and MR T1W can be also encountered.  Absence of
      large intratumoral vessels should not exclude hibernomas from the differential
      diagnosis of regional lipomatous tumors.

PMID- 22613772
TI  - Epigenetic regulation of Arc and c-Fos in the hippocampus after acute
      electroconvulsive stimulation in the rat.
AB  - Electroconvulsive stimulation (ECS) remains one of the most effective treatments
      of major depression. However, the underlying molecular changes still remain to be
      elucidated. Since ECS causes rapid and significant changes in gene expression we
      have looked at epigenetic regulation of two important immediate early genes that
      are both induced after ECS: c-Fos and Arc. We examined Arc and c-Fos protein
      expression and found Arc present over 4 h, in contrast to c-Fos presence lasting
      only 1 h. Both genes had returned to baseline expression at 24 h post-ECS.
      Histone H4 acetylation (H4Ac) is one of the important epigenetic marks associated
      with gene activation. We show increased H4Ac at the c-Fos promoter at 1 h post
      ECS. Surprisingly, we also observed a significant increase in DNA methylation of
      the Arc gene promoter at 24 h post-ECS. DNA methylation, which is responsible for
      gene silencing, is a rather stable covalent modification. This suggests that Arc
      expression has been repressed and may consequently remain inhibited for a
      prolonged period post-ECS. Arc plays a critical role in the maintenance phase of
      long-term potentiation (LTP) and consolidation of memory in the rat brain. Thus,
      this study is one of the first to demonstrate DNA methylation as a regulator of
      ECS-induced gene expression and it provides a molecular link to the memory
      deficits observed after ECS.

PMID- 22613773
TI  - Neuroprotection of co-activation of GABA receptors by preventing caspase-3
      denitrosylation in KA-induced seizures.
AB  - Previous studies have demonstrated that kainic acid (KA)-induced seizures can
      cause the enhancement of excitation and lead to neuronal death in rat
      hippocampus. Co-activation of the inhibitory GABA receptors can attenuate the
      excitatory JNK3 apoptotic signaling pathway via inhibiting the increased assembly
      of the GluR6-PSD-95-MLK3 signaling module induced by KA in epileptic rat
      hippocampal CA1 and CA3 regions. Caspase-3 is a cysteine protease located in both
      the cytoplasm and mitochondrial intermembrane space that is a central effector of
      many apoptotic pathways. We designed experiments to elucidate the underlying
      molecular mechanisms of procaspase-3 activation and neuroprotection of co
      activation of GABA receptors against neuronal death induced by KA. In this study,
      we show that co-activation of GABA receptors can attenuate the Fas/FasL apoptotic
      signaling pathway and inhibit the increased of thioredoxin reductase activity
      induced by KA, subsequently inhibit the activation of procaspase-3 by diminishing
      the denitrosylation of its active-site thiol and decreasing the cleavage of the
      caspase-3 zymogen to its active subunits. These results indicate that co
      activation of GABA receptors results in neuroprotection by preventing caspase-3
      denitrosylation in KA-induced seizure of rats.

PMID- 22613774
TI  - Three-dimensional imaging of the left ventricular outflow tract: impact on aortic
      valve area estimation by the continuity equation.
AB  - BACKGROUND: Measurement of left ventricular outflow tract (LVOT) area for
      estimation of aortic valve area (AVA) using two-dimensional (2D) transthoracic
      echocardiography (TTE) and the continuity equation assumes a round LVOT. The aim
      of this study was to compare measurements of LVOT area and AVA using 2D and three
      dimensional (3D) TTE and cardiac computed tomographic angiography (CCTA) in an
      attempt to improve the accuracy of AVA estimation using TTE. METHODS: Fifty
      patients were prospectively studied, 25 with aortic stenosis and 25 without
      aortic stenosis (group 1). LVOT area and AVA were estimated using 2D TTE, and
      LVOT area and diameters were measured using 256-slice CCTA and 3D TTE. AVA was
      also planimetered using CCTA in midsystole. LVOT area and AVA estimated by 2D TTE
      were correlated with measurements by 3D TTE and CCTA. Findings from group 1 were
      then validated in 38 additional patients with aortic stenosis (group 2). RESULTS:
      LVOTs were oval in 96% of the patients in group 1, with a mean eccentricity index
      (diameter 2/diameter 1) of 1.26 +/- 0.09 by CCTA. Compared with CCTA, 2D TTE
      systematically underestimated LVOT area (and therefore AVA) by 17 +/- 16%. The
      correlation between CCTA and 3D TTE LVOT area was only moderate (r = 0.63),
      because of inadequate 3D transthoracic echocardiographic image quality. Mean AVA
      was 0.92 +/- 0.44 cm(2) by 2D TTE and 1.14 +/- 0.68 cm(2) by CCTA (P = .0015).
      After correcting AVA on 2D TTE by a factor of 1.17 (accounting for LVOT area
      ovality), there was no difference between 2D TTE and CCTA (0.06 +/- 26 cm(2), P =
      .20, r = 0.86). In group 2, 2D TTE underestimated LVOT area and AVA by 16 +/-
      11%, similar to group 1, and AVA by TTE was 0.75 +/- 0.14 cm(2) compared with
      0.88 +/- 0.21 cm(2) by CCTA (P < .0001). When the correction factor was applied
      to the group 2 results, the corrected AVA by 2D TTE (*1.17) was 0.87 +/- 0.17
      cm(2), similar to AVA by CCTA (P = .70). CONCLUSIONS: Three-dimensional imaging
      revealed oval LVOTs in most patients, resulting in underestimation of LVOT area
      and AVA on 2D TTE by 17%. This accounted for the difference in AVA between 2D TTE
      and CCTA. Current 3D TTE is inadequate to accurately measure LVOT area.

PMID- 22613775
TI  - Theta burst TMS increases cerebral blood flow in the primary motor cortex during
      motor performance as assessed by arterial spin labeling (ASL).
AB  - Theta burst stimulation (TBS) is a novel variant of repetitive transcranial
      magnetic stimulation (rTMS), which induces changes in neuronal excitability
      persisting up to 1h. When elicited in the primary motor cortex, such
      physiological modulations might also have an impact on motor behavior. In the
      present study, we applied TBS in combination with pseudo continuous arterial spin
      labeling (pCASL) in order to address the question of whether TBS effects are
      measurable by means of changes in physiological parameters such as cerebral blood
      flow (CBF) and if TBS-induced plasticity can modify motor behavior. Twelve right
      handed healthy subjects were stimulated using an inhibitory TBS protocol at
      subthreshold stimulation intensity targeted over the right motor cortex. The
      control condition consisted of within-subject Sham treatment in a crossover
      design. PCASL was performed before (pre TBS/pre Sham) and immediately after
      treatment (post TBS/post Sham). During the pCASL runs, the subjects performed a
      sequential fingertapping task with the left hand at individual maximum speed.
      There was a significant increase of CBF in the primary motor cortex after TBS,
      but not after Sham. It is assumed that inhibitory TBS induced a "local virtual
      lesion" which leads to the mobilization of more neuronal resources. There was no
      TBS-specific modulation in motor behavior, which might indicate that acute
      changes in brain plasticity caused by TBS are immediately compensated. This
      compensatory reaction seems to be observable at the metabolic, but not at the
      behavioral level.

PMID- 22613777
TI  - Stability of GABAB receptor oligomers revealed by dual TR-FRET and drug-induced
      cell surface targeting.
AB  - The function of cell surface proteins likely involves the formation and
      dissociation of oligomeric complexes. However, the dynamics of this process are
      unknown. Here we examined this process for the GABA(B) receptors that assemble
      into oligomers of heterodimers through the association of their GABA(B1) subunit.
      We report a method to study oligomer dynamics based on a drug-controlled cell
      surface targeting of intracellularly retained receptors and a parallel
      measurement of two FRET signals in HEK293 cells. GABA(B1) subunits at the cell
      surface (4.0 +/- 0.6 a.u.) are labeled with a pair of fluorophores (donor and red
      acceptor). New receptors are then targeted to the cell surface during 3h
      treatment with AP21967 such that the number of receptors is doubled (9.1 +/- 0.7
      a.u.). After labeling these new receptors with a second acceptor (green), the red
      FRET remained unchanged (5189 +/- 36 vs. 4783 +/- 32 cps), supporting the
      stability of the preformed oligomers. However, new oligomers are detected by the
      green FRET signal indicating both receptor populations are in the same
      microdomains. As a control, we confirmed the strict stability of the GABA(B)
      heterodimer itself. Herein, using a novel method to monitor the dynamics of cell
      surface complexes, we provide evidence for the stability of GABA(B) oligomers.

PMID- 22613776
TI  - Neural correlates of emotion regulation deficits in remitted depression: the
      influence of regulation strategy, habitual regulation use, and emotional valence.
AB  - Regulating emotions through reappraisal has been shown to elicit abnormal neural
      activation patterns in currently depressed patients. It is, however, unclear if
      this deficit generalizes to other emotion regulation strategies, if it persists
      when patients recover, and if it is related to habitual use of reappraisal
      strategies. Therefore, we measured the neural responses to emotional images with
      functional magnetic resonance imaging in remitted patients with previous episodes
      of major depression and healthy controls. While viewing the images participants
      regulated the elicited emotions using either a reappraisal or a distraction
      strategy. Habitual reappraisal use was measured with the Cognitive Emotion
      Regulation Questionnaire. Depressed patients showed a selective deficit in down
      regulating amygdala responses to negative emotional stimuli using reappraisal.
      This down-regulation of amygdala activity was strongest in participants high in
      habitual reappraisal use. Activity in the regulating control-network including
      anterior cingulate and lateral orbitofrontal cortex was increased during both
      emotion regulation strategies. The findings in remitted patients with previous
      episodes of major depression suggest that altered emotion regulation is a trait
      marker for depression. This interpretation is supported by the relation of
      habitual reappraisal use to amygdala down-regulation success.

PMID- 22613778
TI  - GHEP-ISFG proficiency test 2011: Paper challenge on evaluation of mitochondrial
      DNA results.
AB  - The GHEP-ISFG Working Group performed a collaborative exercise to monitor the
      current practice of mitochondrial (mt)DNA reporting. The participating
      laboratories were invited to evaluate a hypothetical case example and assess the
      statistical significance of a match between the haplotypes of a case (hair)
      sample and a suspect. A total of 31 forensic laboratories participated of which
      all but one used the EMPOP database. Nevertheless, we observed a tenfold range of
      reported LR values (32-333.4), which was mainly due to the selection of different
      reference datasets in EMPOP but also due to different applied formulae. The
      results suggest the need for more standardization as well as additional research
      to harmonize the reporting of mtDNA evidence.

PMID- 22613779
TI  - Assessment of mock cases involving complex low template DNA mixtures: A
      descriptive study.
AB  - Complex DNA mixtures with low template (LT) components provide the most
      challenging cases to interpret and report. In this study, we designed such
      mixtures and we describe how reporting officers (ROs) at the Netherlands Forensic
      Institute (NFI) assess these when embedded in a mock case setting. DNA mixtures
      containing LT DNA from two to four contributors, sporadic contamination (mimicked
      by adding 6pg of DNA, which represents once cell equivalent) and/or DNA of
      relatives (brothers), were amplified four-fold using the AmpFlSTR((r)) NGMTM PCR
      Amplification Kit. Consensus profiles were then generated which included the
      alleles detected in at least half of the replicates. Four mock cases were created
      by including reference profiles of a hypothetical victim and suspect. The mock
      cases were assessed by eight ROs following the stepwise interpretation approach
      currently in use at the NFI. With this approach, the results of the comparisons
      between the DNA profiles of the evidentiary trace and the reference profiles are
      classified into four categories of evidential value [1]. The interpretations by
      the ROs were compared to the likelihood ratios (LRs) obtained from a
      probabilistic model that allows a calculation of LRs to assist the interpretation
      of LT DNA evidence and both were compared to the true composition of the designed
      mixtures.

PMID- 22613780
TI  - 'I don't have to go to the gym because I ate very healthy today': the development
      of a scale to assess diet-related compensatory health beliefs.
AB  - OBJECTIVE: Nutritional interventions to decrease energy intake, aimed at portion
      sizes and front-of-package labelling, are effective only if people do not
      compensate for their reduced energy intake. Since several observational studies
      indicate that these interventions could prompt compensation behaviour, it is
      important to assess underlying beliefs. Therefore, the purpose of the two studies
      reported here was to develop a Diet-related Compensatory Health Beliefs Scale
      (Diet-CHBS). DESIGN: Cross-sectional surveys were conducted for the scale
      development. Study 1 provided data on the factor analysis and convergent
      validity, while Study 2 assessed the Diet-CHBS' test-retest reliability. Settings
      VU University Amsterdam (Study 1) and twenty-five worksite cafeterias in the
      Netherlands (Study 2). SUBJECTS: Study 1 was conducted among 179 students and
      their parents; Study 2 was conducted among 119 worksite cafeteria visitors.
      RESULTS: The results of Study 1 showed that the scale consisted of the
      hypothesized factors of compensation beliefs with regard to portion sizes (alpha
      = 0.73), front-of-package health logos (alpha = 0.77) and exercise (alpha =
      0.75). The scale's overall Cronbach's alpha was 0.82. The Diet-CHBS had a Pearson
      correlation of 0.32 with a general health compensatory beliefs scale, signifying
      satisfactory convergent validity. Study 2 showed that the intra-class correlation
      coefficient between T1 and T2 was 0.69, indicating adequate test-retest
      reliability. CONCLUSION: The Diet-CHBS is a valid and reliable instrument for
      assessing diet-related compensatory health beliefs in response to nutritional
      interventions. It is important to take such beliefs into account in further
      intervention studies aimed at preventing overweight and obesity.

PMID- 22613781
TI  - Angiotensin II increases corpus cavernosal contractility and oxidative stress in
      partial bladder outlet obstructed rabbits: relevance to erectile dysfunction.
AB  - INTRODUCTION: We investigated the effect angiotensin II (Ang II), a corpus
      cavernosal smooth muscle (CCSM) constrictor peptide, has on tissue taken from
      rabbits following chronic partial bladder outlet obstruction (PBOO), as this
      model is characterized by an increase in corpus cavernosal collagen deposition
      and a marked reduction and impaired relaxation of CCSM cells. AIM: To determine
      the interaction between Ang II and nitric oxide (NO) and the development of
      oxidative stress (OS) in a rabbit model of chronic PBOO. METHODS: Corpus
      cavernosal tissue was obtained from 12 sham-operated and 20 PBOO rabbits. Organ
      bath studies determined Ang II/NO interaction on CCSM function using losartan
      (AT1 receptor antagonist), sodium nitroprusside (SNP, NO donor), electrical field
      stimulation (EFS), and vardenafil (phosphodiesterase type 5 inhibitor). The role
      of OS in the Ang II response was also determined using diphenylene iodonium
      chloride (DPI), the nicotinamide adenine dinucleotide phosphate oxidase
      inhibitor, which inhibits superoxide production and superoxide dismutase (SOD,
      the enzyme that accelerates the breakdown of superoxide). MAIN OUTCOME MEASURE:
      Action of Ang II and AT1 receptor antagonist, as well as SOD and DPI on CCSM
      function. RESULTS: Ang II caused a dose-dependent contraction of CCSM strips that
      was enhanced in PBOO rabbits and inhibited by losartan, DPI, and SOD. CCSM
      relaxation induced by SNP/EFS was impaired in this model and improved by
      vardenafil and losartan. CONCLUSIONS: These findings imply that the increased Ang
      II contractile response is a pathological consequence of PBOO and that AT1
      receptor inhibition may be a therapeutic approach to treat ED associated with
      PBOO.

PMID- 22613782
TI  - Aluminum overload increases oxidative stress in four functional brain areas of
      neonatal rats.
AB  - BACKGROUND: Higher aluminum (Al) content in infant formula and its effects on
      neonatal brain development are a cause for concern. This study aimed to evaluate
      the distribution and concentration of Al in neonatal rat brain following Al
      treatment, and oxidative stress in brain tissues induced by Al overload. METHODS:
      Postnatal day 3 (PND 3) rat pups (n =46) received intraperitoneal injection of
      aluminum chloride (AlCl3), at dosages of 0, 7, and 35 mg/kg body wt (control, low
      Al (LA), and high Al (HA), respectively), over 14 d. RESULTS: Aluminum
      concentrations were significantly higher in the hippocampus (751.0 +/- 225.8 ng/g
      v.s. 294.9 +/- 180.8 ng/g; p < 0.05), diencephalon (79.6 +/- 20.7 ng/g v.s. 20.4
      +/- 9.6 ng/g; p < 0.05), and cerebellum (144.8 +/- 36.2 ng/g v.s. 83.1 +/- 15.2
      ng/g; p < 0.05) in the HA group compared to the control. The hippocampus,
      diencephalon, cerebellum, and brain stem of HA animals displayed significantly
      higher levels of lipid peroxidative products (TBARS) than the same regions in the
      controls. However, the average superoxide dismutase (SOD) activities in the
      cerebral cortex, hippocampus, cerebellum, and brain stem were lower in the HA
      group compared to the control. The HA animals demonstrated increased catalase
      activity in the diencephalon, and increased glutathione peroxidase (GPx) activity
      in the cerebral cortex, hippocampus, cerebellum, and brain stem, compared to
      controls. CONCLUSION: Aluminum overload increases oxidative stress (H2O2) in the
      hippocampus, diencephalon, cerebellum, and brain stem in neonatal rats.

PMID- 22613783
TI  - Crosstalk between TGF-beta signaling and the microRNA machinery.
AB  - The activin/transforming growth factor-beta (TGF-beta) pathway plays an important
      role in tumorigenesis either by its tumor suppressor or tumor promoting effect.
      Loss of members of the TGF-beta signaling by somatic mutations or epigenetic
      events, such as DNA methylation or regulation by microRNA (miRNA), may affect the
      signaling process. Most members of the TGF-beta pathway are known to be targeted
      by one or more miRNAs. In addition, the biogenesis of miRNAs is also regulated by
      TGF-beta both directly and through SMADs. Based on these interactions, it appears
      that autoregulatory feedback loops between TGF-beta and miRNAs influence the fate
      of tumor cells. Our aim is to review the crosstalk between TGF-beta signaling and
      the miRNA machinery to highlight potential novel therapeutic targets.

PMID- 22613784
TI  - HCN2 ion channels: an emerging role as the pacemakers of pain.
AB  - Acute nociceptive pain is caused by the direct action of a noxious stimulus on
      pain-sensitive nerve endings, whereas inflammatory pain (both acute and chronic)
      arises from the actions of a wide range of inflammatory mediators released
      following tissue injury. Neuropathic pain, which is triggered by nerve damage, is
      often considered to be very different in its origins, and is particularly
      difficult to treat effectively. Here we review recent evidence showing that
      members of the hyperpolarization-activated cyclic nucleotide-modulated (HCN) ion
      channel family - better known for their role in the pacemaker potential of the
      heart - play important roles in both inflammatory and neuropathic pain. Deletion
      of the HCN2 isoform from nociceptive neurons abolishes heat-evoked inflammatory
      pain and all aspects of neuropathic pain, but acute pain sensation is unaffected.
      This work shows that inflammatory and neuropathic pain have much in common, and
      suggests that selective blockers of HCN2 may have value as analgesics in the
      treatment of pain.

PMID- 22613785
TI  - Photoperiod effects on the expression of kisspeptin and gonadotropin genes in
      Atlantic cod, Gadus morhua, during first maturation.
AB  - In order to investigate the potential role of the kisspeptin system in the
      entrainment of reproduction in Atlantic cod, qPCR assays were developed for kiss2
      and its receptor kissr4. mRNA expression was monitored in the brain over a full
      reproductive cycle in 2 populations of males and females: 1) a maturing
      population (exposed to simulated natural photoperiod, SNP) and 2) a maturation
      inhibited population (exposed to constant light, LL). Pituitary expression of
      gonadotropin subunit mRNA (fshbeta and lhbeta) was also measured. Results from
      this study indicated no clear temporal pattern in expression of kiss2 or kissr4
      mRNAs in either population of cod, however acute elevations were apparent in
      maturing (SNP) individuals, namely an elevation in kiss2 in vitellogenic females
      and spermiating males and spikes in kissr4 during early vitellogenesis in females
      and spermatogenesis in males. Gonadotropin mRNA expression displayed strong
      amplitudinal changes over time with fshbeta and lhbeta mRNA expression increasing
      towards spawning in maturing individuals. No firm conclusions on the role of the
      kisspeptin system in cod puberty can be drawn at this stage, however mRNA
      increases in kiss2 and kissr4 may elude to conserved kisspeptin functions in cod
      and opens up interesting avenues on potential gender specific functions.

PMID- 22613786
TI  - The trade-off between maturation and growth during accelerated development in
      frogs.
AB  - Developmental energetics are crucial to a species' life history and ecology but
      are poorly understood from a mechanistic perspective. Traditional energy and mass
      budgeting does not distinguish between costs of growth and maturation, making it
      difficult to account for accelerated development. We apply a metabolic theory
      that uniquely considers maturation costs (Dynamic Energy Budget theory, DEB) to
      interpret empirical data on the energetics of accelerated development in
      amphibians. We measured energy use until metamorphosis in two related frogs,
      Crinia georgiana and Pseudophryne bibronii. Mass and energy content of fresh ova
      were comparable between the species. However, development to metamorphosis was
      1.7 times faster in C. georgiana while P. bibronii produced nine times the dry
      biomass at metamorphosis and had lower mass-specific oxygen requirements. DEB
      theory explained these patterns through differences in ontogenetic energy
      allocation to maturation. P. bibronii partitioned energy in the same (constant)
      way throughout development whereas C. georgiana increased the fraction of energy
      allocated to maturation over growth between hatching and the onset of feeding.
      DEB parameter estimation for additional, direct-developing taxa suggests that a
      change in energy allocation during development may result from a selective
      pressure to increase development rate, and not as a result of development mode.

PMID- 22613787
TI  - Effect of fasting on the structure and function of the gastrointestinal tract of
      house sparrows (Passer domesticus).
AB  - Starvation is a condition that often affects animals in nature. The
      gastrointestinal tract is the organ system displaying the most rapid and dramatic
      changes in response to nutrient deprivation. To date, little is known about
      starvation phases and effects on the organ morphology and digestive function in
      small passerine birds. In this study, we determined the phases of starvation and
      examined the effect of final stage of starvation in the organ morphology and,
      intestinal histology and enzymatic function in the small intestine. Our results
      show the three phases of the classical model of fasting in a shorter period of
      time. The mass of heart, pancreas, stomach, small intestine and liver of long
      term fasted birds was reduced between 20 and 47%. The mass decrease in small
      intestine was correlated with reduction in small intestinal histology: perimeter,
      mucosal thickness, villus height and width. In contrast, the enzyme activity of
      sucrase-isomaltase and aminopeptidase-N in enterocytes, all expressed per MUg of
      protein, was higher in long-term fasted birds than fed animals. This suggest
      that, while autophagy of digestive organs is induced by starvation, consistent
      with phenotypic plasticity, the activity of sucrase-isomaltase and aminopeptidase
      N remains high, probably as an anticipatory strategy to optimize digestion at re
      feeding time.

PMID- 22613788
TI  - Obligate biotroph parasitism: can we link genomes to lifestyles?
AB  - Although the oomycetes and fungi are evolutionarily very distantly related, both
      taxa evolved biotrophy on plant hosts several times independently, giving rise to
      rust- and mildew-like phenotypes. Differences in host colonization and adaptation
      may be reflected in genome size and by gain and loss of genes. In this opinion
      article we combine classical knowledge with recently sequenced pathogen genomes
      and present new hypotheses about the convergent evolution that led to these two
      distinct phenotypes in obligate biotrophs.

PMID- 22613789
TI  - Development of recombinant single-chain variable fragment against hepatitis A
      virus and its use in quantification of hepatitis A antigen.
AB  - Phage display technology has been utilized for identification of specific binding
      molecules to an antigenic target thereby enabling the rapid generation and
      selection of high affinity, fully human antibodies directed towards disease
      target appropriate for antibody therapy. In the present study, single chain Fv
      antibody fragment (scFv) to hepatitis A virus (HAV) was selected from phage
      displayed antibody library constructed from peripheral blood lymphocytes (PBLs)
      of a vaccinated donor. The variable heavy (V(H)) and light chains (V(L)) were
      amplified using cDNA as template, assembled into scFv using splicing by overlap
      extension PCR (SOE PCR) and cloned into phagemid vector as a fusion for display
      of scFv on bacteriophage. The phage displaying antibody fragments were subjected
      to three rounds of panning with HAV antigen on solid phase. High affinity
      antibodies reactive to hepatitis A virus were identified by phage ELISA and
      cloned into a bacterial expression vector pET20b. The scFv was purified by
      immobilized metal affinity chromatography (IMAC) on a nickel-nitrilotriacetic
      acid (NTA) agarose column and characterized. The binding activity and specificity
      of the scFv was established by its non-reactivity towards other human viral
      antigens as determined by ELISA and immunoblot analysis. The scFv was further
      used in the development of an in-house IC-ELISA format in combination with a
      commercially available mouse monoclonal antibody for the quantification of
      hepatitis A virus antigen in human vaccine preparations. The adjusted r2 values
      obtained by subjecting the values obtained by quantification of the NIBSC
      standards using the commercial and the in-house ELISA kits by regression analysis
      were 0.99 and 0.95. 39 vaccine samples were subjected to quantification using
      both the kits. Regressional statistical analysis through the origin of the
      samples indicated International Unit (IU) values of 0.0416x and 0.0419x,
      respectively for the commercial and in-house kit respectively.

PMID- 22613790
TI  - Association of endometriosis risk and genetic polymorphisms involving
      biosynthesis of sex steroids and their receptors: an updating meta-analysis.
AB  - The objective of our study is to assess the association of endometriosis risk and
      genetic polymorphisms involving biosynthesis of sex steroids and their receptors.
      A systematic search of three databases was conducted. Twenty-seven studies on the
      association of the cytochrome P450 subfamily 17 (CYP17), estrogen receptor gene
      (ER), progesterone receptor gene (PR), 17-beta-hydroxysteroid dehydrogenase type
      1 gene (HSD17B1), and cytochrome P450 subfamily 19 (CYP19) polymorphisms with
      endometriosis risk were identified. When all groups were pooled, we found an
      association between HSD17B1 (A variant allele vs. G wild allele: odds ratio
      (OR)=1.42, 95% confidence interval (CI)=1.10-1.84, P=0.007) and PR (P2 variant
      allele vs. P1 wild allele, OR=1.43, 95% CI=0.99-2.08, P=0.058) polymorphisms and
      endometriosis risk, while failing to detect links with CYP17, ER, and CYP19
      polymorphisms examined. In the subgroup analysis, a significant association of
      CYP17 and ERalpha-PvuII polymorphisms with endometriosis was found neither in a
      Caucasian population nor in an Asian population. The findings of our study
      suggest that HSD17B1 and PR polymorphisms are associated with an increased risk
      of endometriosis. Further investigation into the association between CYP17, ER,
      PR, HSD17B1, and CYP19 polymorphisms and endometriosis risk is warranted and
      should include larger sample sizes.

PMID- 22613791
TI  - The degree of BCR and NFAT activation predicts clinical outcomes in chronic
      lymphocytic leukemia.
AB  - B-cell antigen receptor (BCR)-mediated signaling plays a critical role in chronic
      lymphocytic leukemia (CLL) pathogenesis and gives an in vitro survival advantage
      to B cells isolated from patients with unfavorable prognostic factors. In this
      study, we undertook to elucidate the signaling intermediates responsible for this
      biologic alteration. In responding cells only, in vitro BCR engagement triggers
      global phosphorylation of Syk, activation of phospholipase Cgamma2, and
      intracellular calcium mobilization, reflecting competency of BCR signaling. The
      calcium-calcineurin-dependent transcription factor NFAT2 is up-regulated and to
      some extent constitutively activated in all CLL B cells. In contrast, its DNA
      binding capacity is enhanced on IgM stimulation in responding cells only. NFAT
      inhibition using the VIVIT peptide prevents induction of CD23 target gene and IgM
      induced survival, converting responding cells to unresponsive status. At the
      opposite, ionomycin-induced NFAT activity allows survival of nonresponding cells.
      These results demonstrate that the functional heterogeneity relies on variability
      of protein levels establishing BCR-dependent thresholds and NFAT-dependent
      activation. Finally, status of the BCR-NFAT pathway for each patient reveals its
      relevance for CLL clinical outcome and points out to BCR-NFAT intermediates as
      promising functional therapeutic targets.

PMID- 22613792
TI  - Conservative mutations in the C2 domains of factor VIII and factor V alter
      phospholipid binding and cofactor activity.
AB  - Factor VIII and factor V share structural homology and bind to phospholipid
      membranes via tandem, lectin-like C domains. Their respective C2 domains bind via
      2 pairs of hydrophobic amino acids and an amphipathic cluster. In contrast, the
      factor V-like, homologous subunit (Pt-FV) of a prothrombin activator from
      Pseudonaja textilis venom is reported to function without membrane binding. We
      hypothesized that the distinct membrane-interactive amino acids of these proteins
      contribute to the differing membrane-dependent properties. We prepared mutants in
      which the C2 domain hydrophobic amino acid pairs were changed to the homologous
      residues of the other protein and a factor V mutant with 5 amino acids changed to
      those from Pt-FV (FV(MTTS/Y)). Factor VIII mutants were active on additional
      membrane sites and had altered apparent affinities for factor X. Some factor V
      mutants, including FV(MTTS/Y), had increased membrane interaction and apparent
      membrane-independent activity that was the result of phospholipid retained during
      purification. Phospholipid-free FV(MTTS/Y) showed increased activity,
      particularly a 10-fold increase in activity on membranes lacking
      phosphatidylserine. The reduced phosphatidylserine requirement correlated to
      increased activity on resting and stimulated platelets. We hypothesize that
      altered membrane binding contributes to toxicity of Pt-FV.

PMID- 22613793
TI  - How I treat newly diagnosed chronic phase CML.
AB  - The progress made in the understanding of chronic myeloid leukemia (CML) since
      the recognition of a common chromosomal abnormality to the introduction of ever
      more effective tyrosine kinase inhibitors is unprecedented in cancer. The
      expected survival for patients diagnosed with CML today, if properly managed, is
      probably similar to that of the general population. When managing patients with
      CML the goal is to achieve the best long-term outcome and we should base the
      treatment decisions on the data available. The results from cytogenetic and
      molecular analyses have to be interpreted judiciously and all available treatment
      options integrated into the treatment plan properly. The availability of several
      treatment options in CML is an asset, but the temptation of rapid succession of
      treatment changes because of perceived suboptimal response or for adverse events
      that could be managed needs to be avoided. Any decision to change therapy needs
      to weigh the expected long-term outcome with the current option versus the true
      expectations with any new option, particularly as it relates to irreversible
      outcomes, such as transformation to blast phase and death. In this manuscript, we
      discuss the treatment approach that has helped us manage successfully a large CML
      population.

PMID- 22613794
TI  - The origin and function of platelet glycosyltransferases.
AB  - Platelets are megakaryocyte subfragments that participate in hemostatic and host
      defense reactions and deliver pro- and antiangiogenic factors throughout the
      vascular system. Although they are anucleated cells that lack a complex secretory
      apparatus with distinct Golgi/endoplasmic reticulum compartments, past studies
      have shown that platelets have glycosyltransferase activities. In the present
      study, we show that members of 3 distinct glycosyltransferase families are found
      within and on the surface of platelets. Immunocytology and flow cytometry results
      indicated that megakaryocytes package these Golgi-derived glycosyltransferases
      into vesicles that are sent via proplatelets to nascent platelets, where they
      accumulate. These glycosyltransferases are active, and intact platelets
      glycosylate large exogenous substrates. Furthermore, we show that activation of
      platelets results in the release of soluble glycosyltransferase activities and
      that platelets contain sufficient levels of sugar nucleotides for detection of
      glycosylation of exogenously added substrates. Therefore, the results of the
      present study show that blood platelets are a rich source of both
      glycosyltransferases and donor sugar substrates that can be released to function
      in the extracellular space. This platelet-glycosylation machinery offers a
      pathway to a simple glycoengineering strategy improving storage of platelets and
      may serve hitherto unknown biologic functions.

PMID- 22613795
TI  - Thrombopoietin/MPL participates in initiating and maintaining RUNX1-ETO acute
      myeloid leukemia via PI3K/AKT signaling.
AB  - Oncogenic mutations in components of cytokine signaling pathways elicit ligand
      independent activation of downstream signaling, enhancing proliferation and
      survival in acute myeloid leukemia (AML). The myeloproliferative leukemia virus
      oncogene, MPL, a homodimeric receptor activated by thrombopoietin (THPO), is
      mutated in myeloproliferative disorders but rarely in AML. Here we show that wild
      type MPL expression is increased in a fraction of human AML samples expressing
      RUNX1-ETO, a fusion protein created by chromosome translocation t(8;21), and that
      up-regulation of Mpl expression in mice induces AML when coexpressed with RUNX1
      ETO. The leukemic cells are sensitive to THPO, activating survival and
      proliferative responses. Mpl expression is not regulated by RUNX1-ETO in mouse
      hematopoietic progenitors or leukemic cells. Moreover, we find that activation of
      PI3K/AKT but not ERK/MEK pathway is a critical mediator of the MPL-directed
      antiapoptotic function in leukemic cells. Hence, this study provides evidence
      that up-regulation of wild-type MPL levels promotes leukemia development and
      maintenance through activation of the PI3K/AKT axis, and suggests that inhibitors
      of this axis could be effective for treatment of MPL-positive AML.

PMID- 22613796
TI  - Epitope targeting and viral inoculum are determinants of Nef-mediated immune
      evasion of HIV-1 from cytotoxic T lymphocytes.
AB  - The impact of HIV-1 Nef-mediated HLA-I down-regulation on CD8(+) cytotoxic T
      lymphocytes (CTLs) varies by epitope, but the determining factors have not been
      elucidated. In the present study, we investigated the impact of Nef on the
      antiviral efficiency of HIV-1-specific CTLs targeting 17 different epitopes to
      define properties that determine susceptibility to Nef. The impact of Nef was not
      correlated with the presenting HLA-I type or functional avidity of CTLs, but
      instead was related directly to the kinetics of infected cell clearance. Whereas
      Gag-specific CTLs generally were less susceptible to Nef than those targeting
      other proteins, this was determined by the ability to eliminate infected cells
      before de novo synthesis of viral proteins, which was also observed for CTLs
      targeting a Nef epitope. This very early clearance of infected cells depended on
      virus inoculum, and the required inoculum varied by epitope. These results
      suggest that whereas Gag-specific CTLs are more likely to recognize infected
      cells before Nef-mediated HLA-I down-regulation, this varies depending on the
      specific epitope and virus inoculum. Reduced susceptibility to Nef therefore may
      contribute to the overall association of Gag-specific CTL responses to better
      immune control if a sufficient multiplicity of infection is attained in vivo, but
      this property is not unique to Gag.

PMID- 22613797
TI  - SAP expression in invariant NKT cells is required for cognate help to support B
      cell responses.
AB  - One of the manifestations of X-linked lymphoproliferative disease (XLP) is
      progressive agammaglobulinemia, caused by the absence of a functional signaling
      lymphocyte activation molecule (SLAM)-associated protein (SAP) in T, invariant
      natural killer T (NKT) cells and NK cells. Here we report that alpha
      galactosylceramide (alphaGalCer) activated NKT cells positively regulate antibody
      responses to haptenated protein antigens at multiple checkpoints, including
      germinal center formation and affinity maturation. Whereas NKT cell-dependent B
      cell responses were absent in SAP(-/-).B6 mice that completely lack NKT cells,
      the small number of SAP-deficient NKT cells in SAP(-/-).BALB/c mice adjuvated
      antibody production, but not the germinal center reaction. To test the hypothesis
      that SAP-deficient NKT cells can facilitate humoral immunity, SAP was deleted
      after development in SAP(fl/fl).tgCreERT2.B6 mice. We find that NKT cell
      intrinsic expression of SAP is dispensable for noncognate helper functions, but
      is critical for providing cognate help to antigen-specific B cells. These results
      demonstrate that SLAM-family receptor-regulated cell-cell interactions are not
      limited to T-B cell conjugates. We conclude that in the absence of SAP, several
      routes of NKT cell-mediated antibody production are still accessible. The latter
      suggests that residual NKT cells in XLP patients might contribute to variations
      in dysgammaglobulinemia.

PMID- 22613799
TI  - Critical role of CD4 T cells in maintaining lymphoid tissue structure for immune
      cell homeostasis and reconstitution.
AB  - Loss of the fibroblastic reticular cell (FRC) network in lymphoid tissues during
      HIV-1 infection has been shown to impair the survival of naive T cells and limit
      immune reconstitution after antiretroviral therapy. What causes this FRC loss is
      unknown. Because FRC loss correlates with loss of both naive CD4 and CD8 T-cell
      subsets and decreased lymphotoxin-beta, a key factor for maintenance of FRC
      network, we hypothesized that loss of naive T cells is responsible for loss of
      the FRC network. To test this hypothesis, we assessed the consequences of
      antibody-mediated depletion of CD4 and CD8 T cells in rhesus macaques and sooty
      mangabeys. We found that only CD4 T-cell depletion resulted in FRC loss in both
      species and that this loss was caused by decreased lymphotoxin-beta mainly
      produced by the CD4 T cells. We further found the same dependence of the FRC
      network on CD4 T cells in HIV-1-infected patients before and after antiretroviral
      therapy and in other immunodeficiency conditions, such as CD4 depletion in cancer
      patients induced by chemotherapy and irradiation. CD4 T cells thus play a central
      role in the maintenance of lymphoid tissue structure necessary for their own
      homeostasis and reconstitution.

PMID- 22613800
TI  - Formation of BCR oligomers provides a mechanism for B cell affinity
      discrimination.
AB  - B cells encounter antigen over a wide affinity range, from K(A)=10(5) M(-1) to
      K(A)=10(10) M(-1). The strength of B cell antigen receptor (BCR) signaling in
      response to antigen increases with affinity, a process known as "affinity
      discrimination". In this work, we use a computational simulation of B cell
      surface dynamics and membrane-proximal signaling to show that affinity
      discrimination can arise from the formation of BCR oligomers. It is known that
      BCRs form oligomers upon encountering antigen, and that the size and rate of
      formation of these oligomers both increase with affinity. In our simulation, we
      have introduced a requirement that only BCR-antigen complexes that are part of an
      oligomer can engage cytoplasmic signaling molecules such as Src-family kinases.
      Our simulation shows that as affinity increases, BCR signaling activity increases
      in addition to the number of collected antigen. Our results are also consistent
      with the existence of an experimentally-observed threshold affinity of activation
      at K(A)=10(5)-10(6) M(-1) (no signaling activity below this affinity value) and
      affinity discrimination ceiling of K(A)=10(10) M(-1) (no affinity discrimination
      above this affinity value). Comparison with experiments shows that the time scale
      of BCR oligomer formation predicted by our model (less than 10 s) is well within
      the time scale of experimentally observed association of BCR with Src-family
      kinases (10-20 s).

PMID- 22613801
TI  - Full-length genomic analysis of porcine G9P[23] and G9P[7] rotavirus strains
      isolated from pigs with diarrhea in South Korea.
AB  - Group A rotaviruses (RVAs) are agents causing severe gastroenteritis in infants
      and young animals. G9 RVA strains are believed to have originated from pigs.
      However, this genotype has emerged as the fifth major human RVA genotype
      worldwide. To better understand the relationship between human and porcine RVA
      strains, complete RVA genome data are needed. For human RVA strains, the number
      of complete genome data have grown exponentially. However, there is still a lack
      of complete genome data on porcine RVA strains. Recently, G9 RVA strains have
      been identified as the third most important genotype in diarrheic pigs in South
      Korea in combinations with P[7] and P[23]. This study is the first report on
      complete genome analyses of 1 G9P[7] and 3 G9P[23] porcine RVA strains, resulting
      in the following genotype constellation: G9-P[7]/P[23]-I5-R1-C1-M1-A8-N1-T1-E1
      H1. By comparisons of these genotype constellations, it was revealed that the
      Korean G9P[7] and G9P[23] RVA strains possessed a typical porcine RVA backbone,
      similar to other known porcine RVA strains. However, detailed phylogenetic
      analyses revealed the presence of intra-genotype reassortments among porcine RVA
      strains in South Korea. Thus, our data provide genetic information of G9 RVA
      strains increasingly detected in both humans and pigs, and will help to establish
      the role of pigs as a source or reservoir for novel human RVA strains.

PMID- 22613798
TI  - Eri1 regulates microRNA homeostasis and mouse lymphocyte development and
      antiviral function.
AB  - Natural killer (NK) cells play a critical role in early host defense to infected
      and transformed cells. Here, we show that mice deficient in Eri1, a conserved 3'
      to-5' exoribonuclease that represses RNA interference, have a cell-intrinsic
      defect in NK-cell development and maturation. Eri1(-/-) NK cells displayed
      delayed acquisition of Ly49 receptors in the bone marrow (BM) and a selective
      reduction in Ly49D and Ly49H activating receptors in the periphery. Eri1 was
      required for immune-mediated control of mouse CMV (MCMV) infection. Ly49H(+) NK
      cells deficient in Eri1 failed to expand efficiently during MCMV infection, and
      virus-specific responses were also diminished among Eri1(-/-) T cells. We
      identified miRNAs as the major endogenous small RNA target of Eri1 in mouse
      lymphocytes. Both NK and T cells deficient in Eri1 displayed a global, sequence
      independent increase in miRNA abundance. Ectopic Eri1 expression rescued
      defective miRNA expression in mature Eri1(-/-) T cells. Thus, mouse Eri1
      regulates miRNA homeostasis in lymphocytes and is required for normal NK-cell
      development and antiviral immunity.

PMID- 22613803
TI  - Arterial sampler filling time during arterial and venous punctures, and its
      relationship with mean arterial pressure in human subjects.
AB  - BACKGROUND: When obtaining an arterial blood sample via percutaneous puncture,
      there is a risk of accidentally obtaining venous blood. Conventional methods of
      confirming arterial blood at the bedside, such as blood color and pulsatile
      return, can be misleading in patients with low blood  pressure or hypoxemia.
      OBJECTIVE: To determine if the arterial sampler filling time can be an accurate
      indicator of obtaining an arterial blood sample in subjects with various blood
      pressures. Our hypotheses were that there would be a statistically significant
      negative correlation between  sampler filling time during arterial puncture and
      mean arterial blood pressure, and a statistically significant difference between
      venous and arterial filling times in human adults. METHODS: Prior to an arterial
      puncture, we measured and recorded arterial blood pressure noninvasively. During 
      the arterial and venipuncture procedures we measured the amount of time it took
      to fill the sampler and the volume of blood obtained. A t test for independent
      samples was calculated to determine if mean arterial sampler filling times were
      significantly different between the arterial  and venous groups. Pearson
      correlation coefficient was calculated to determine the relationship between mean
      arterial pressure and seconds of filling time per milliliter in the arterial
      group. RESULTS: This study included 38 human subjects; 22 were adult patients
      ordered for arterial blood  gases by arterial puncture; 16 were normal, healthy,
      adult volunteers who had a venipuncture performed using an arterial blood
      sampler. The mean +/- SD filling time was 15 +/- 4 s/mL for the arterial group
      and 115 +/- 48 s/mL for the venous group, and the difference was significant  (P
      < .001). The range of mean arterial pressures was 69-125 mm Hg; the average mean
      arterial pressure was 91 +/- 13 mm Hg, and the Pearson correlation coefficient
      for mean arterial pressures and sampler filling times was -0.49 (P = .02).
      CONCLUSION: Our  results were consistent with a laboratory study showing a
      significant difference between arterial and venous filling times and a negative
      correlation between mean arterial pressure and sampler filling time, but our
      times in adult subjects were longer. Respiratory therapists may find arterial 
      sampler filling time as a useful indicator of successful arterial puncture at the
      bedside.

PMID- 22613802
TI  - A genome-wide analysis of lentivector integration sites using targeted sequence
      capture and next generation sequencing technology.
AB  - One application of next-generation sequencing (NGS) is the targeted resequencing
      of interested genes which has not been used in viral integration site analysis of
      gene therapy applications. Here, we combined targeted sequence capture array and
      next generation sequencing to address the whole genome profiling of viral
      integration sites. Human 293T and K562 cells were transduced with a HIV-1 derived
      vector. A custom made DNA probe sets targeted pLVTHM vector used to capture
      lentiviral vector/human genome junctions. The captured DNA was sequenced using GS
      FLX platform. Seven thousand four hundred and eighty four human genome sequences
      flanking the long terminal repeats (LTR) of pLVTHM fragment sequences matched
      with an identity of at least 98% and minimum 50 bp criteria in both cells. In
      total, 203 unique integration sites were identified. The integrations in both
      cell lines were totally distant from the CpG islands and from the transcription
      start sites and preferentially located in introns. A comparison between the two
      cell lines showed that the lentiviral-transduced DNA does not have the same
      preferred regions in the two different cell lines.

PMID- 22613804
TI  - Impact of normalization method on experimental outcome using RT-qPCR in
      Staphylococcus aureus.
AB  - We performed a gene expression study using RT-qPCR in Staphylococcus aureus. The
      influence of normalization method was investigated. We confirmed that a recent
      standard, using more reference genes, was the best normalization strategy. The
      application of the most commonly used reference genes in 2011 (gyrB and 16S rRNA
      gene) failed.

PMID- 22613805
TI  - Q&A: 'toxic' effects of sugar: should we be afraid of fructose?

PMID- 22613806
TI  - Polyps originating from accessory middle turbinate and secondary middle
      turbinate.
AB  - OBJECTIVE: We report two extremely rare cases of polyps from unilateral accessory
      middle turbinates, one of which coexisted with a polyp from an inferomedially
      projecting, pneumatised, secondary middle turbinate. METHODS: Case report and
      literature review concerning accessory middle turbinate and secondary middle
      turbinate. RESULTS: Two patients presented with unilateral nasal obstruction. In
      both patients, nasal endoscopy revealed polypoid masses originating from the
      middle meatus. Paranasal sinus computed tomography and histopathological analysis
      confirmed the presence of polyps originating from an accessory middle turbinate
      and secondary middle turbinate, which were resected uneventfully via endoscopic
      sinus surgery. CONCLUSION: To our knowledge, this is the first report in the
      world literature of polyps originating from a unilateral accessory middle
      turbinate and secondary middle turbinate. Pre-operative recognition of these rare
      anatomical variations is of particular importance in avoiding intra-operative
      complication.

PMID- 22613807
TI  - Study on the hypoglycemic activities and metabolism of alcohol extract of
      Alismatis Rhizoma.
AB  - The Alisma rhizoma is widely used in the therapy of diabetes in traditional folk
      medicine of China. Compositional analysis of the alcohol extract of Alismatis
      Rhizoma (AEA) revealed that the eight compounds gotten from AEA are all belonging
      to protostane-type triterpenes. The AEA and compounds were incubated with 3T3-L1
      preadipocytes, glucose level in the 3T3-L1 adipocytes culture medium and lipid
      content in 3T3-L1 adipocytes were measured, and analysis of alpha-glucosidase
      inhibition of AEA and compounds. At the same time, the uptake of AEA by 3T3-L1
      adipocytes and the metabolism of AEA in SD rats were analyzed by HPLC-ESI/MS. As
      result, AEA increased glucose uptake in 3T3-L1 adipocyte model, not increase
      adipogenesis; AEA inhibited alpha-glucosidase activity; alisol A-24-aceate (8)
      was absorbed by 3T3-L1 adipocytes; and two compounds were detected in blood and
      three were detected in urine in SD rats. So AEA had protostane-type triterpenes,
      these type compounds in AEA may have hypoglycemic activity via inhibition of
      alpha-glucosidase activity and promotion of glucose uptake. In contrast to the
      anti-diabetic drug thiazolidinediones, they did not induce adipogenesis, avoiding
      the displeased effects of rosiglitazone.

PMID- 22613808
TI  - Cytoprotective effects of phlorofucofuroeckol A isolated from Ecklonia
      stolonifera against tacrine-treated HepG2 cells.
AB  - We have recently reported that phlorofucofuroeckol A isolated from Ecklonia
      stolonifera showed potential antioxidative and anti-inflammatory properties in
      LPS-stimulated macrophages. This study aims to investigate the cytoprotective
      effect of phlorofucofuroeckol A and to characterize its molecular mechanisms
      using tacrine-treated HepG2 cells. Phlorofucofuroeckol A showed a cytoprotective
      effect against tacrine-treated HepG2 cells in a dose-dependent manner (EC(50):
      5.7+/-0.5 MUM). Increased intracellular reactive oxygen species (ROS) by tacrine
      were decreased by phlorofucofuroeckol A. The cytotoxicity of tacrine to HepG2
      cells was associated with upregulations of Fas and JNK phosphorylation resulted
      in the caspase activations and apoptosis. Phlorofucofuroeckol A inhibited the
      phosphorylation of JNK and the expression of Fas-mediated apoptotic proteins
      including Fas ligand, cleaved caspase-8, cleaved caspase-3, and poly (ADP-ribose)
      polymerase. In addition, treatment of phlorofucofuroeckol A regulated the release
      of cytochrome c from mitochondria to cytosol in a dose-dependent manner in
      tacrine-treated HepG2 cells. Furthermore, pretreatment of an inhibitor of JNK,
      SP600125, downregulated Fas and cleaved caspase-3 without change of ROS
      productions in tacrine-treated HepG2 cells. In conclusion, our study demonstrated
      that phlorofucofuroeckol A regulates Fas-mediated apoptosis via inhibition of ROS
      productions and inhibition of JNK phosphorylation in tacrine-treated HepG2 cells.

PMID- 22613809
TI  - Frequent activation of EGFR in advanced chordomas.
AB  - BACKGROUND: Chordomas are rare neoplasms, arising from notochordal remnants in
      the midline skeletal axis, for which the current treatment is limited to surgery
      and radiotherapy.  Recent reports suggest that receptor tyrosine kinases (RTK)
      might be essential for the survival or proliferation of chordoma cells, providing
      a rationale for RTK targeted therapy.  Nevertheless, the reported data are
      conflicting, most likely due to the assorted tumor specimens used for the studies
      and the heterogeneous methodological approaches.  In the present study, we
      performed a comprehensive characterization of this rare entity using a wide range
      of assays in search for relevant therapeutic targets. METHODS: Histopathological
      features of 42 chordoma specimens, 21 primary and 21 advanced, were assessed by
      immunohistochemistry and fluorescent in situ hybridization (FISH) using PDGFRB,
      CSF1R, and EGFR probes.  Twenty-two of these cases, for which frozen material was
      available (nine primary and 13 advanced tumors), were selectively analyzed using
      the whole-genome 4.3K TK-CGH-array, phospho-kinase antibody array or Western
      immunoblotting.  The study was supplemented by direct sequencing of KIT, PDGFRB,
      CSF1R and EGFR. RESULTS: We demonstrated that EGFR is frequently and the most
      significantly activated RTK in chordomas.  Furthermore, concurrent to EGFR
      activation, the tumors commonly reveal co-activation of alternative RTK.  The
      consistent activation of AKT, the frequent loss of the tumor suppressor PTEN
      allele, the recurrent activation of upstream RTK and of downstream effectors like
      p70S6K and mTOR, all indicate the PI3K/AKT pathway as an important mediator of
      transformation in chordomas. CONCLUSIONS: Given the complexity of the signaling
      in chordomas, combined treatment regimens targeting multiple RTK and downstream
      effectors are likely to be the most effective in these tumors.  Personalized
      therapy with careful selection of the patients, based on the molecular profile of
      the specific tumor, is anticipated.

PMID- 22613810
TI  - Which kind of transition is important for sound representation? An event-related
      potential study.
AB  - Auditory transients (such as sound onset or a frequency transition within a
      continuous sound) are assumed to parse the auditory input into smaller units
      enabling the formation of unitary sound representations separately for each
      segment. This was discovered by using the mismatch negativity (MMN) component of
      the event-related potential (ERP) that taps into auditory sensory memory
      representations. For unstructured sounds, MMN amplitude decreased or even
      vanished with increasing the temporal distance of an irregular feature (deviance,
      e.g. duration decrement) relative to the onset of an otherwise regularly
      occurring sound, whereas for sounds that were segmented by a transient, MMN
      persisted. It has been speculated that the P1-N1-P2 complex, indexing the sensory
      encoding of the transient, determines the temporal units of the acoustic input
      that are represented by the information processing system. To test this
      hypothesis, we utilized a previously reported asymmetry in the sensory encoding
      of physically identical but time-reversed transitions between segments of
      constant and gliding frequency. In separate blocks, we regularly presented 1400
      ms sounds with a centered constant-to-glide or glide-to-constant transition.
      Occasionally and unpredictably, one of the regularly occurring sounds was
      shortened in duration to 910 ms. We found larger transition-related P1-N1-P2
      potentials accompanied by larger deviance-related MMN amplitudes for sounds with
      constant-to-glide transition than for sounds with glide-to-constant transition.
      This provides evidence that it is the precise sensory encoding of the transition
      which is crucial for automatically parsing the auditory input into smaller units,
      thus enabling the formation of unitary sound representations even for late
      segments.

PMID- 22613811
TI  - Upgrading of the micro-marsupialisation technique for the management of mucus
      extravasation or retention phenomena.
AB  - This study evaluated the performance of an upgrading of the micro
      marsupialisation technique for the management of mucus extravasation or retention
      phenomena. This study presents a prospective case series of management of ranulas
      and mucoceles, with a follow-up ranging from 6 to 18 months. Data included the
      age and gender of patients, as well as the type, size, and site of lesions, and
      number of punctures. The treatment performance was evaluated according to:
      postoperative pain, oedema, secondary infection, clinical healing, retreatment,
      and recurrence of the lesions. All patients showed clinical healing of the
      lesions within 30 days after the micro-marsupialisation technique. None of
      patients presented a recurrence or required retreatment, there was no oedema or
      infection. No pain, or mild pain was reported by the majority of patients
      (58.81%). Micro-marsupialisation proved to be a simple, low cost, relatively non
      invasive, painless, effective, and low recurrence technique to treat mucus
      extravasation or retention phenomena. Micro-marsupialisation can be recommended
      primarily to treat oral ranulas and selected mucoceles.

PMID- 22613812
TI  - Regulation of developmental competence and commitment towards the definitive
      endoderm lineage in human embryonic stem cells.
AB  - Human embryonic stem cells (hESCs) can self-renew and become all three germ
      layers. Nodal/Activin signaling specifies developmental status in hESCs: moderate
      Nodal/Activin signaling maintains pluripotency, while enhancement and inhibition
      promote definitive endoderm (DE) and neuroectoderm (NE) development,
      respectively. However, how modulation of Nodal/Activin signaling influences
      developmental competence and commitment toward specific lineages is still
      unclear. Here, we showed that enhancement of Nodal/Activin signaling for 4 days
      was necessary and sufficient to upregulate DE markers, while it diminished the
      upregulation of NE markers by inhibition of Nodal/Activin signaling. This
      suggests that after 4 days of enhanced Nodal/Activin signaling, hESCs are
      committed to the DE lineage and have lost competence toward the NE lineage. In
      contrast, inhibition of Nodal/Activin signaling using LY364947 for 2 days was
      sufficient to impair competence toward the DE lineage, although cells were still
      able to activate LEFTY1 and NODAL, direct targets of Nodal/Activin signaling.
      Expression analyses indicated that the levels of pluripotency regulators NANOG
      and POU5F1 were significantly diminished by 2 days of LY364947 treatment,
      although the expression of NANOG, but not POU5F1, was restored immediately upon
      Activin A treatment. Thus, downregulation of POU5F1 coincided with the abrogation
      of DE competence caused by inhibition of Nodal/Activin signaling.

PMID- 22613813
TI  - Does gynecologic malignancy predict likelihood of a tertiary palliative care unit
      hospital admission? A comparison of local, provincial and national death rates.
AB  - OBJECTIVE: The purpose of this study was to determine whether the presence of
      gynecologic malignancies predicts the likelihood of a tertiary palliative care
      unit hospital admission. METHOD: In this study, patients admitted to a
      specialized tertiary palliative care unit (TPCU) with gynecologic malignancies
      were compared to national and provincial death rates to determine if gynecologic
      malignancy predicts admission, and subsequent death, in a TPCU. RESULTS: Eighty
      two gynecologic cancer patients were admitted to our TPCU over the 5- year study
      period. Out of all cancer deaths in the TPCU, death from ovarian cancer was 3.7%
      compared with 2.4% (p = 0.0068) of all cancer deaths in Manitoba and 2.3% (p =
      0.0043) of all cancer deaths in Canada. Cervical cancer accounted for 1.7% of all
      our patients deaths compared with 0.7% (p = 0.0001) provincially and 0.6% (p =
      0.0001) nationally. Uterine cancer deaths were not significantly different from
      the provincial and national death rates, whereas vulvar and fallopian cancers
      were too rare to allow for statistical analysis. SIGNIFICANCE OF RESULTS:
      Gynecologic cancers may be predictive of admission to a palliative care unit.

PMID- 22613814
TI  - A neutral theory of genome evolution and the frequency distribution of genes.
AB  - BACKGROUND: The gene composition of bacteria of the same species can differ
      significantly between isolates. Variability in gene composition can be summarized
      in terms of gene frequency distributions, in which individual genes are ranked
      according to the frequency of genomes in which they appear. Empirical gene
      frequency distributions possess a U-shape, such that there are many rare genes,
      some genes of intermediate occurrence, and many common genes. It would seem that
      U-shaped gene frequency distributions can be used to infer the essentiality
      and/or importance of a gene to a species. Here, we ask: can U-shaped gene
      frequency distributions, instead, arise generically via neutral processes of
      genome evolution? RESULTS: We introduce a neutral model of genome evolution which
      combines birth-death processes at the organismal level with gene uptake and loss
      at the genomic level. This model predicts that gene frequency distributions
      possess a characteristic U-shape even in the absence of selective forces driving
      genome and population structure. We compare the model predictions to empirical
      gene frequency distributions from 6 multiply sequenced species of bacterial
      pathogens. We fit the model with constant population size to data, matching U
      shape distributions albeit without matching all quantitative features of the
      distribution. We find stronger model fits in the case where we consider
      exponentially growing populations. We also show that two alternative models which
      contain a "rigid" and "flexible" core component of genomes provide strong fits to
      gene frequency distributions. CONCLUSIONS: The analysis of neutral models of
      genome evolution suggests that U-shaped gene frequency distributions provide less
      information than previously suggested regarding gene essentiality. We discuss the
      need for additional theory and genomic level information to disentangle the roles
      of evolutionary mechanisms operating within and amongst individuals in driving
      the dynamics of gene distributions.

PMID- 22613815
TI  - Characterization of bmp15 and its regulation by human chorionic gonadotropin in
      the follicle of gibel carp (Carassius auratus gibelio).
AB  - Bone morphogenetic protein (BMP15) is a member of the transforming growth factor
      beta (TGF-beta) superfamily with a key role in regulating follicle development in
      mammals and birds. However, potential ovarian roles of BMPs remain unexplored in
      teleosts. In this study, the full-length sequences of bmp15 were obtained using
      rapid-amplification of cDNA ends (RACE). The full-length cDNA sequence of bmp15
      is 2217 bp which contained 214 bp 5'-UTR and 845 bp 3'-UTR. The open reading
      frame (ORF) sequence of bmp15 is 1158 bp, encoding a predicted protein of 385
      amino acid residues. BMP15 has a specific RXXR protease cleavage site of TGF-beta
      superfamily (is RIRR) and six conserved cysteine residues. Using real-time
      quantitative PCR revealed that bmp15 mRNA was largely expressed in the ovary and
      testis and mostly in oocytes within the follicle, slightly expressed in muscle,
      liver and pituitary. BMP15 is mainly present at stage I follicles by real-time
      quantitative PCR and immunohistochemistry. Phylogenetic analysis showed that
      gibel carp bmp15 was similar to bmp15 of zebrafish and other fish species.
      Treatment with human chorionic gonadotropin (hCG) in isolated follicles of gibel
      carp in vitro showed altered bmp15 mRNA expression: when treated with 10 ng/mL
      hCG for 10h, the expression level of bmp15 was significantly increased. However,
      with proceeding cultivation, the expression level of BMP15 mRNA decreased. The
      results of this study indicate that bmp15 may play a key role during development
      of follicles in gibel carp, especially in early stage follicles.

PMID- 22613817
TI  - Molecular characterization of three crustin genes in the morotoge shrimp,
      Pandalopsis japonica.
AB  - Crustins are among the most important antimicrobial peptides (AMPs) found in
      decapod crustaceans. They are small cationic AMPs (5-7 kDa) characterized by a
      proline-rich amino-terminal domain and a cysteine-rich carboxyl-terminal domain.
      Here, the first 3 crustin-like cDNAs (Pj-crus Ia, Ib, and II) were identified
      from the morotoge shrimp, Pandalopsis japonica. The full-length cDNAs of Pj-crus
      Ia, Ib, and II consisted of 1135, 580, and 700 nucleotides and encoded putative
      proteins containing 109, 119, and 186 amino acids residues, respectively. All 3
      identified Pj-crus sequences exhibited the conserved domain organization for
      crustins, including a signal sequence, a cysteine-containing region, a glycine
      rich region, and a whey-acidic protein (WAP) domain. Amino acid sequence
      comparisons and phylogenetic analysis revealed that the Pj-crus Ia and Ib belong
      to type I crustins (e.g., carcinin), which have been mostly identified from
      Brachyura and Astacidea, whereas Pj-crus II was classified as belonging to the
      type II crustins, which are mainly found in Dendrobranchiata. An analysis of the
      organization of these 3 Pj-crus genes revealed that the splicing site within the
      WAP domain may be an important key for classifying types I and II crustin family
      members. The tissue distribution profile results showed that the Pj-crus I genes
      were expressed in a tissue-specific manner but that the Pj-crus II gene was
      expressed ubiquitously, suggesting that these crustins may play different roles
      in various tissues or under different physiological conditions. The bacterial
      challenge results suggested that the Pj-crus genes may be transcriptionally
      influenced by different bacterial types. This comparative study of various
      crustin family members will help extend the knowledge on the crustacean innate
      immune response, which will provide important basic information for controlling
      shrimp immunity against various pathogens.

PMID- 22613816
TI  - Comparative enzymology of (2S,4R)4-fluoroglutamine and (2S,4R)4-fluoroglutamate.
AB  - Many cancer cells have a strong requirement for glutamine. As an aid for
      understanding this phenomenon the (18)F-labeled 2S,4R stereoisomer of 4
      fluoroglutamine [(2S,4R)4-FGln] was previously developed for in vivo positron
      emission tomography (PET). In the present work, comparative enzymological studies
      of unlabeled (2S,4R)4-FGln and its deamidated product (2S,4R)4-FGlu were
      conducted as an adjunct to these PET studies. Our findings are as follows: Rat
      kidney preparations catalyze the deamidation of (2S,4R)4-FGln. (2,4R)4-FGln and
      (2S,4R)4-FGlu are substrates of various aminotransferases. (2S,4R)4-FGlu is a
      substrate of glutamate dehydrogenase, but not of sheep brain glutamine
      synthetase. The compound is, however, a strong inhibitor of this enzyme. Rat
      liver cytosolic fractions catalyze a gamma-elimination reaction with (2S,4R)4
      FGlu, generating alpha-ketoglutarate. Coupling of a deamidase reaction with this
      gamma-elimination reaction provides an explanation for the previous detection of
      (18)F(-) in tumors exposed to [(18)F](2S,4R)4-FGln. One enzyme contributing to
      this reaction was identified as alanine aminotransferase, which catalyzes
      competing gamma-elimination and aminotransferase reactions with (2S,4R)4-FGlu.
      This appears to be the first description of an aminotransferase catalyzing a
      gamma-elimination reaction. The present results demonstrate that (2S,4R)4-FGln
      and (2S,4R)4-FGlu are useful analogues for comparative studies of various
      glutamine- and glutamate-utilizing enzymes in normal and cancerous mammalian
      tissues, and suggest that tumors may metabolize (2S,4R)4-FGln in a generally
      similar fashion to glutamine. In plants, yeast and bacteria a major route for
      ammonia assimilation involves the consecutive action of glutamate synthase plus
      glutamine synthetase (glutamate synthase cycle). It is suggested that (2S,4R)4
      FGln and (2S,4R)4-FGlu will be useful probes in studies of ammonia assimilation
      by the glutamate synthase pathway in these organisms. Finally, glutamine
      transaminases are conserved in mammals, plants and bacteria, and probably serve
      to close the methionine salvage pathway, thus linking nitrogen metabolism to
      sulfur metabolism and one-carbon metabolism. It is suggested that (2S,4R)4-FGln
      may be useful in studies of the methionine salvage pathway in a variety of
      organisms.

PMID- 22613818
TI  - Seasonal variations of biochemical, pigment, fatty acid, and sterol compositions
      in female Crassostrea corteziensis oysters in relation to the reproductive cycle.
AB  - Wild female Crassostrea corteziensis oyster (n=245) were analyzed over one year
      to understand the main ecophysiological events associated to gonad development.
      Different indicators (mainly biochemical) were analyzed to infer: i) utilization
      and accumulation of energy reserves (e.g. neutral lipids, carbohydrates,
      proteins; vitellogenin), ii) membrane components provided by the diet as
      essential nutrients and indicative of cell proliferation (e.g. highly unsaturated
      fatty acids linked to phospholipids, sterols), iii) indicators of food
      availability (chlorophyll a in water, pigments in tissues, specific fatty acids
      and sterols), iv) gonad development (e.g. gonad coverage area, vitellin). A PCA
      analysis was applied to 269 measured variables. The first PC (PC1) was composed
      of total carbohydrate and lipid concentration, percentage of esterified sterols,
      fatty acids specific of diatoms; 16:1n-7/16:0, 20:5n-3 in neutral lipids with
      positive loadings and non methylene-interrupted fatty acids (NMI) in neutral
      lipids with negative loadings. The second PC (PC2) was composed of 18:4n-3 in
      lipid reserves and the concentration of zeaxanthin, a pigment typical of
      cyanobacteria with positive loadings and the proportion of 20:4n-6 in polar
      lipids with negative loading. The third PC (PC3) was composed of gonad coverage
      area (GCA) and the concentration of vitellin. Variation in GCA confirms that
      gonad development began in April with an extended period of spawning and
      rematuration from April to November. The PCA further shows that a second period
      of minimal maturation from November to March corresponds to the accumulation of
      reserves (PC1) together with an initial high availability of food (PC2) at the
      beginning of this period. These two periods are in accordance with the classical
      periods of allocation of energy to reserves followed by gonad development
      reported for several mollusks.

PMID- 22613819
TI  - The control of the balance between ceramide and sphingosine-1-phosphate by
      sphingosine kinase: oxidative stress and the seesaw of cell survival and death.
AB  - Sphingolipids are components of all eukaryotic cells that play important roles in
      a wide variety of biological processes. Ceramides and sphingosine-1-phosphate
      (S1P) are signaling molecules that regulate cell fate decisions in a wide array
      of species including yeast, plants, vertebrates, and invertebrates. Ceramides
      favor anti-proliferative and cell death pathways such as senescence and
      apoptosis, whereas S1P stimulates cell proliferation and survival pathways. The
      control of cell fate by these two interconvertible lipids has been called the
      sphingolipid rheostat or sphingolipid biostat. Sphingosine kinase, the enzyme
      that synthesizes S1P, is a crucial enzyme in regulation of the balance of these
      sphingolipids. Sphingosine kinase has been shown to play dynamic roles in the
      responses of cells to stress, leading to modulation of cell fate through a
      variety of signaling pathways impinging on the processes of cell proliferation,
      apoptosis, autophagy and senescence. This review summarizes the roles of
      sphingosine kinase signaling in these processes and the mechanisms mediating
      these responses. In addition, we discuss the evidence tying sphingosine kinase
      mediated stress responses to the process of aging.

PMID- 22613820
TI  - Abundance of myostatin gene transcripts and their correlation with muscle
      hypertrophy during the development of barramundi, Lates calcarifer.
AB  - Myostatin (MSTN) is a pivotal protein that regulates vertebrate muscle growth and
      development. Teleost fish possess two MSTN paralogs (MSTN-1 and MSTN-2) whose
      respective physiological functions are still largely unclear. To clarify the role
      of each of these paralogs the transcript abundance of Mstn-1 and Mstn-2 was
      quantified during embryonic and larval development of the teleosts, barramundi,
      Lates calcarifer. Histological analyses of developing muscle fibers were also
      obtained to correlate Mstn paralog expression with muscle hypertrophy as larvae
      undergo metamorphosis. Mstn-1 and Mstn-2 transcripts were detected as early as
      immediately postfertilization of eggs, with the level of expression observed to
      increase during embryonic development and reach a peak near hatching. Mstn-2
      expression was thousands-fold higher than that observed for Mstn-1. Close to
      metamorphosis, the expression of Mstn-1 was non-significantly, although
      positively associated, with muscle hypertrophy (r=0.384, p=0.064), while that of
      Mstn-2 showed a highly significant negative correlation (r=-0.691, p<0.0001)
      suggesting that this paralog may be responsible for muscle hypertrophy that
      occurs post-metamorphosis. Altogether, findings from this study support the
      hypothesis that Mstn paralogs are differentially regulated during various phases
      of fish development and that they may have evolved different functions in fish,
      particularly that related to muscle hypertrophy.

PMID- 22613821
TI  - Surface-based multi-template automated hippocampal segmentation: application to
      temporal lobe epilepsy.
AB  - In drug-resistant temporal lobe epilepsy (TLE), detecting hippocampal atrophy on
      MRI is crucial as it allows defining the surgical target. In addition to atrophy,
      about 40% of patients present with malrotation, a developmental anomaly
      characterized by atypical morphologies of the hippocampus and collateral sulcus.
      We have recently shown that both atrophy and malrotation impact negatively the
      performance of volume-based techniques. Here, we propose a novel hippocampal
      segmentation algorithm (SurfMulti) that integrates deformable parametric
      surfaces, vertex-wise modeling of locoregional texture and shape, and multiple
      templates in a unified framework. To account for inter-subject variability,
      including shape variants, we used a library derived from a large database of
      healthy (n=80) and diseased (n=288) hippocampi. To quantify malrotation, we
      generated 3D models from manual hippocampal labels and automatically extracted
      collateral sulci. The accuracy of SurfMulti was evaluated relative to manual
      labeling and segmentation obtained through a single atlas-based algorithm
      (FreeSurfer) and a volume-based multi-template approach (Vol-multi) using the
      Dice similarity index and surface-based shape mapping, for which we computed
      vertex-wise displacement vectors between automated and manual segmentations. We
      then correlated segmentation accuracy with malrotation features and atrophy.
      SurfMulti outperformed FreeSurfer and Vol-multi, and achieved a level of accuracy
      in TLE patients (Dice=86.9%) virtually identical to healthy controls
      (Dice=87.5%). Vertex-wise shape mapping showed that SurfMulti had an excellent
      overlap with manual labels, with sub-millimeter precision. Its performance was
      not influenced by atrophy or malrotation (|r|<0.20, p>0.2), while FreeSurfer
      (|r|>0.35, p<0.0001) and Vol-multi (|r|>0.28, p<0.05) were hampered by both
      anomalies. The magnitude of atrophy detected using SurfMulti was the closest to
      manual volumetry (Cohen's d: manual=1.71, t=7.6; SurfMulti=1.60, t=7.0; Vol
      multi=1.38, t=6.1; FreeSurfer=0.91, t=3.9). The high performance of SurfMulti
      regardless of cohort, atrophy and shape variants identifies this algorithm as a
      robust segmentation tool for hippocampal volumetry.

PMID- 22613822
TI  - Spring-mass behavior and electromyographic activity evolution during a cycle-run
      test to exhaustion in triathletes.
AB  - PURPOSE: To evaluate spring-mass (SM) behavior and associated electromyographic
      (EMG) activity during a run to exhaustion following a cycle exercise in trained
      triathletes. METHODS: Ten triathletes completed four tests: a cycling test to
      determine VO(2max); a running test to determine the lactate threshold (LT); a 5
      min control run at LT (C-Run) followed after a total recovery period by a cycle
      to-run session to exhaustion [30 min of cycling at ~80% VO(2max) followed by a
      run until exhaustion at LT (T-Run)]. SM behavior and EMG signals in nine lower
      limb muscles were recorded throughout the running sessions. RESULTS: Immediately
      after cycling, leg stiffness was 12.1% higher than its C-Run value and a
      concomitant increase of EMG activity of knee extensors was observed during pre
      contact. Throughout T-Run, leg stiffness decreased by 7.3%, while knee extensors
      and ankle flexors activities decreased during pre-contact and braking phases. No
      significant variations in SM parameters and no significant increase of muscle
      activity were reported between C-Run and the end of T-Run. CONCLUSION: SM
      behavior during the cycle-run test was consistent with EMG activity changes.
      Cessation of exercise was not associated with significant alterations of
      stiffness values and EMG activity.

PMID- 22613823
TI  - The effect of perspiration on the sEMG amplitude and power spectrum.
AB  - Sweat accumulation underneath surface EMG (sEMG) electrodes is a common problem
      in workplace studies which compromises electrode adherence to the skin as well as
      signal fidelity. In this study, the effect of sweat accumulation on signal
      amplitude and mean frequency (MF) was examined to determine if the sEMG signal
      becomes altered through the sweat layer and whether this effect can be avoided by
      interrupting the pool of sweat using a thin strip of medical adhesive between the
      electrode snaps. Nine males performed a maximum, isometric contraction of their
      right quadriceps as sEMG was collected. Skin conditions under the electrode were
      dry and wet in incremental layers of 0.02 mm of artificial sweat. The results
      demonstrated that sweat accumulation under sEMG electrodes dampens the amplitude
      of the EMG signal in a predictable way (r = .88 and .97 for double and single
      snap electrodes, respectively) with almost 2% and 3% deterioration for every 0.02
      mm of sweat depending on the type of electrode used. The medical adhesive proved
      to be highly effective at preventing amplitude deterioration indicating that
      signal shunting can be prevented. MF was not influenced by sweat accumulation
      even under the extreme wet condition.

PMID- 22613824
TI  - [Wnt pathway and sclerostin as new targets for assessment and treatment of
      osteoporosis].
AB  - The increasing knowledge of bone biology has allowed the identification of new
      intracellular pathways involved in the regulation of remodelling and osteoblast
      activity. In this respect, the characterization of the Wnt pathway has been a
      breakthrough for its involvement and role in disorders of mineral metabolism. A
      better understanding of these signaling pathways may allow the development of new
      diagnostic markers and new drugs for metabolic bone disease, where despite
      extensive available therapies, unmet needs still persist. In this review, we make
      an approach to the discovery and functions of the Wnt pathway with a focus on
      bone effects. Next, we briefly review the main data about their endogenous
      antagonist, sclerostin, precisely where drug research is more advanced.

PMID- 22613825
TI  - [First case in Spain of bacteremia by Methylobacterium thiocyanatum from Hickmann
      catheter in an immunosuppressed patient with Hodgkin's lymphoma].

PMID- 22613826
TI  - [A 67 year-old male with abdominal pain, splenomegaly, lymphadenopathies, and
      bone density changes].

PMID- 22613827
TI  - [Impairment of the general status in a 70-year-old man].

PMID- 22613828
TI  - [Influence of clinical and biographical factors on the delay in starting adjuvant
      chemotherapy treatment among breast cancer patients].
AB  - BACKGROUND AND OBJECTIVE: Previous studies have related the delay in starting
      chemotherapy (>3 months from date of surgery) with worse survival. The study
      objective is to analyse the delay in the start of chemotherapy and associated
      biomedical, sociodemographic and cultural factors. PATIENTS AND METHODS: A cohort
      of women operated on for breast cancer, candidates for receiving adjuvant
      chemotherapy and participants in a clinical trial of non-pharmacological
      intervention, were surveyed regarding the delay in starting their chemotherapy,
      measured by the number of days from date of surgery. Differences in function of
      the clinical and biographical variables were studied. RESULTS: In 197 women, mean
      delay was 42.32 (15.29) days; this was associated with tumour stage (i, 40.06
      days; ii, 44.76 days; iii, 38.7 days; P=.049), age (<= 35, 37.36 days; 36-64,
      41.49 days; >= 65, 52.61 days; P=.007) and occupational situation (active, 36.91
      days; unemployed, 45.5 days; pensioner, 40.07 days; housewife, 43.17 days;
      P=.038). For patients older than 65 years, the delay in starting adjuvant
      chemotherapy was longer than for those in the 2 lower age groups -less than 35
      years, and between 35 and 65 years- (P=.023 and P=.009 respectively). In the
      multivariate analysis, the variables associated independently with the delay in
      starting chemotherapy were again age (P=.019), tumour stage (P=.037) and
      occupational situation (P=.022). CONCLUSION: Patients began receiving adjuvant
      chemotherapy within the time period (3 months from surgery) defined as
      appropriate, and during which no evidence exists of worse survival results.
      Length of delay varied according to age, tumour stage and occupational situation.

PMID- 22613829
TI  - [Unexpected diagnosis in the case of a 16-year-old boy with back pain].

PMID- 22613830
TI  - [About the use of non-invasive mechanical ventilation].

PMID- 22613832
TI  - TBC1D14 regulates autophagosome formation via Rab11- and ULK1-positive recycling
      endosomes.
AB  - Autophagy is a bulk degradation process characterized by the formation of double
      membrane vesicles called autophagosomes. The exact molecular mechanism of
      autophagosome formation and the origin of the autophagosomal membrane remain
      unclear. We screened 38 human Tre-2/Bub2/Cdc16 domain-containing Rab guanosine
      triphosphatase-activating proteins (GAPs) and identified 11 negative regulators
      of starvation-induced autophagy. One of these putative RabGAPs, TBC1D14,
      colocalizes and interacts with the autophagy kinase ULK1. Overexpressed TBC1D14
      tubulates ULK1-positive recycling endosomes (REs), impairing their function and
      inhibiting autophagosome formation. TBC1D14 binds activated Rab11 but is not a
      GAP for Rab11, and loss of Rab11 prevents TBC1D14-induced tubulation of REs.
      Furthermore, Rab11 is required for autophagosome formation. ULK1 and Atg9 are
      found on Rab11- and transferrin (Tfn) receptor (TfnR)-positive recycling
      endosomes. Amino acid starvation causes TBC1D14 to relocalize from REs to the
      Golgi complex, whereas TfnR and Tfn localize to forming autophagosomes, which are
      ULK1 and LC3 positive. Thus, TBC1D14- and Rab11-dependent vesicular transport
      from REs contributes to and regulates starvation-induced autophagy.

PMID- 22613833
TI  - Basement membrane assembly of the integrin alpha8beta1 ligand nephronectin
      requires Fraser syndrome-associated proteins.
AB  - Dysfunction of the basement membrane protein QBRICK provokes Fraser syndrome,
      which results in renal dysmorphogenesis, cryptophthalmos, syndactyly, and
      dystrophic epidermolysis bullosa through unknown mechanisms. Here, we show that
      integrin alpha8beta1 binding to basement membranes was significantly impaired in
      Qbrick-null mice. This impaired integrin alpha8beta1 binding was not a direct
      consequence of the loss of QBRICK, which itself is a ligand of integrin
      alpha8beta1, because knock-in mice with a mutation in the integrin-binding site
      of QBRICK developed normally and do not exhibit any defects in integrin
      alpha8beta1 binding. Instead, the loss of QBRICK significantly diminished the
      expression of nephronectin, an integrin alpha8beta1 ligand necessary for renal
      development. In vivo, nephronectin associated with QBRICK and localized at the
      sublamina densa region, where QBRICK was also located. Collectively, these
      findings indicate that QBRICK facilitates the integrin alpha8beta1-dependent
      interactions of cells with basement membranes by regulating the basement membrane
      assembly of nephronectin and explain why renal defects occur in Fraser syndrome.

PMID- 22613834
TI  - Stoichiometry of Nck-dependent actin polymerization in living cells.
AB  - Regulation of actin dynamics through the Nck/N-WASp (neural Wiskott-Aldrich
      syndrome protein)/Arp2/3 pathway is essential for organogenesis, cell
      invasiveness, and pathogen infection. Although many of the proteins involved in
      this pathway are known, the detailed mechanism by which it functions remains
      undetermined. To examine the signaling mechanism, we used a two-pronged strategy
      involving computational modeling and quantitative experimentation. We developed
      predictions for Nck-dependent actin polymerization using the Virtual Cell
      software system. In addition, we used antibody-induced aggregation of membrane
      targeted Nck SH3 domains to test these predictions and to determine how the
      number of molecules in Nck aggregates and the density of aggregates affected
      localized actin polymerization in living cells. Our results indicate that the
      density of Nck molecules in aggregates is a critical determinant of actin
      polymerization. Furthermore, results from both computational simulations and
      experimentation support a model in which the Nck/N-WASp/Arp2/3 stoichiometry is
      4:2:1. These results provide new insight into activities involving localized
      actin polymerization, including tumor cell invasion, microbial pathogenesis, and
      T cell activation.

PMID- 22613835
TI  - The C-terminal tail domain of metavinculin, vinculin's splice variant, severs
      actin filaments.
AB  - Vinculin and its splice variant, metavinculin (MV), are key elements of multiple
      protein assemblies linking the extracellular matrix to the actin cytoskeleton.
      Vinculin is expressed ubiquitously, whereas MV is mainly expressed in smooth and
      cardiac muscle tissue. The only difference in amino acid sequence between the
      isoforms is a 68-residue insert in the C-terminal tail domain of MV (MVt).
      Although the functional role of this insert remains elusive, its importance is
      exemplified by point mutations that are associated with dilated and hypertrophic
      cardiomyopathy. In vinculin, the actin binding site resides in the tail domain.
      In this paper, we show that MVt binds actin filaments similarly to the vinculin
      tail domain. Unlike its splice variant, MVt did not bundle actin filaments.
      Instead, MVt promoted severing of actin filaments, most efficiently at
      substoichiometric concentrations. This surprising and seemingly contradictory
      alteration of vinculin function by the 68-residue insert may be essential for
      modulating compliance of vinculin-induced actin bundles when exposed to rapidly
      increasing external forces.

PMID- 22613837
TI  - Euphol, a tetracyclic triterpene produces antinociceptive effects in inflammatory
      and neuropathic pain: the involvement of cannabinoid system.
AB  - Persistent pains associated with inflammatory and neuropathic states are
      prevalent and debilitating diseases, which still remain without a safe and
      adequate treatment. Euphol, an alcohol tetracyclic triterpene, has a wide range
      of pharmacological properties and is considered to have anti-inflammatory action.
      Here, we assessed the effects and the underlying mechanisms of action of euphol
      in preventing inflammatory and neuropathic pain. Oral treatment with euphol (30
      and 100 mg/kg) reduced carrageenan-induced mechanical hyperalgesia. Likewise,
      euphol given through the spinal and intracerebroventricular routes prevented
      mechanical hyperalgesia induced by carrageenan. Euphol consistently blocked the
      mechanical hyperalgesia induced by complete Freund's adjuvant, keratinocyte
      derived chemokine, interleukin-1beta, interleukin-6 and tumor necrosis factor
      alpha associated with the suppression of myeloperoxidase activity in the mouse
      paw. Oral treatment with euphol was also effective in preventing the mechanical
      nociceptive response induced by ligation of the sciatic nerve and also
      significantly reduced the levels and mRNA of cytokines/chemokines in both paw and
      spinal cord tissues following i.pl. injection of complete Freund's adjuvant. In
      addition, the pre-treatment with either CB1R or CB2R antagonists, as well as the
      knockdown gene of the CB1R and CB2R, significantly reversed the antinociceptive
      effect of euphol. Interestingly, even in higher doses, euphol did not cause any
      relevant action in the central nervous system. Considering that few drugs are
      currently available for the treatment of chronic pain states, the present results
      provided evidence that euphol constitutes a promising molecule for the management
      of inflammatory and neuropathic pain states.

PMID- 22613836
TI  - Mgr2 promotes coupling of the mitochondrial presequence translocase to partner
      complexes.
AB  - Many mitochondrial proteins are synthesized with N-terminal presequences in the
      cytosol. The presequence translocase of the inner mitochondrial membrane (TIM23)
      translocates preproteins into and across the membrane and associates with the
      matrix-localized import motor. The TIM23 complex consists of three core
      components and Tim21, which interacts with the translocase of the outer membrane
      (TOM) and the respiratory chain. We have identified a new subunit of the TIM23
      complex, the inner membrane protein Mgr2. Mitochondria lacking Mgr2 were
      deficient in the Tim21-containing sorting form of the TIM23 complex. Mgr2 was
      required for binding of Tim21 to TIM23(CORE), revealing a binding chain of
      TIM23(CORE)-Mgr2/Tim21-respiratory chain. Mgr2-deficient yeast cells were
      defective in growth at elevated temperature, and the mitochondria were impaired
      in TOM-TIM23 coupling and the import of presequence-carrying preproteins. We
      conclude that Mgr2 is a coupling factor of the presequence translocase crucial
      for cell growth at elevated temperature and for efficient protein import.

PMID- 22613839
TI  - The novel calpain inhibitor A-705253 prevents stress-induced tau
      hyperphosphorylation in vitro and in vivo.
AB  - Calcium-mediated pathologic activation of the cysteine protease calpain has been
      linked to neurodegenerative disorders such as Alzheimer's disease (AD) through
      the cleavage of proteolytic substrates that negatively affect neuronal function.
      Hyperphosphorylation of the microtubule-associated protein tau and the subsequent
      aggregation of tau filaments resulting in the intracellular formation of
      neurofibrillary tangles are recognized as key etiological factors in AD
      pathology. Cyclin-dependent kinase 5 (Cdk5), a major kinase responsible for tau
      hyperphosphorylation in the AD brain, becomes hyperactivated through calpain
      mediated cleavage-conversion of the Cdk5 regulatory protein p35 to p25. In the
      present study, we examined the effects of the novel small-molecule calpain
      inhibitor A-705253 in acute models of tau hyperphosphorylation in vitro and in
      vivo. In hippocampal slices in vitro, lowering medium temperature to 33  degrees
      C increased tau phosphorylation in which incubation with A-705253 blocked low
      temperature-induced tau phosphorylation as measured by Western blot analysis.
      Pentobarbital-induced hypothermia or acute systemic LPS treatment in normal mice
      increased tau phosphorylation in hippocampal CA3 mossy fibers, as measured by
      immunohistochemistry, whereas acute A-705253 pretreatment prevented the stress
      induced tau hyperphosphorylation in both models. In support of a Cdk5-mediated
      mechanism, A-705253 administered for two weeks in the drinking water of six month
      old prepathogenic 3x Tg-AD mice resulted in decreased expression of the calpain
      proteolytic p25 fragment. Taken together, results of these studies suggest that
      calpain inhibition has potential utility in reducing tau hyperphosphorylation and
      may represent a novel disease-modifying approach in the treatment of AD.

PMID- 22613838
TI  - Effect of ganaxolone and THIP on operant and limited-access ethanol self
      administration.
AB  - Recent evidence suggests that GABA(A) receptor ligands may regulate ethanol
      intake via effects at both synaptic and extrasynaptic receptors. For example, the
      endogenous neurosteroid, allopregnanolone (ALLO) has a similar pharmacological
      profile as ethanol, and it alters ethanol intake in rodent models. Additionally,
      recent evidence suggests that delta-subunit-containing extrasynaptic GABA(A)
      receptors may confer high sensitivity to both ethanol and neurosteroids. The
      purpose of the present study was to determine the effects of ganaxolone (GAN; an
      ALLO analog) and gaboxadol (THIP; a GABA(A) receptor agonist with selectivity for
      the extrasynaptic delta-subunit) on ethanol intake, drinking patterns, and bout
      characteristics in operant and limited-access self-administration procedures. In
      separate studies, the effects of GAN (0-10 mg/kg) and THIP (2-16 mg/kg) were
      tested in C57BL/6J male mice provided with 2-h access to a two-bottle choice of
      water or 10% ethanol or trained to respond for 30 min of access to 10% ethanol.
      GAN had no overall significant effect on operant ethanol self-administration, but
      tended to decrease the latency to consume the first bout. In the limited-access
      procedure, GAN dose-dependently decreased ethanol intake. THIP dose-dependently
      decreased ethanol intake in both paradigms, altering both the consummatory and
      appetitive processes of operant self-administration as well as shifting the
      drinking patterns in both procedures. These results add to literature suggesting
      time-dependent effects of neurosteroids to promote the onset, and to subsequently
      decrease, ethanol drinking behavior, and they support a role for extrasynaptic
      GABA(A) receptor activation in ethanol reinforcement.

PMID- 22613840
TI  - Fetal longitudinal myocardial function assessment by anatomic M-mode.
AB  - AIM: To evaluate the feasibility of offline anatomic M-mode (AMM) to study fetal
      atrioventricular annulus long-axis displacement (LAD) and compare its performance
      against real-time conventional M-mode (MM). MATERIAL AND METHODS: Paired AMM and
      MM LAD studies were recorded prospectively in 54 fetuses, and performance was
      compared. Insonation angles were less than 30 degrees  in all but 4 cases. The
      overall feasibility of AMM was tested in a composite total sample of 91 normal
      singleton pregnancies (median gestational age 23+6 weeks, range 12-36). AMM LAD
      was measured by placement of a virtual M-mode line on digitally stored raw data
      of fetal 4-chamber video loops. We studied annulus LAD at the lateral mitral
      (left ventricle; LV), proximal mitral (intraventricular septum; IVS), and lateral
      tricuspid (right ventricle; RV) myocardial segments. We compared LAD and its
      regression with gestational age measured using both methods in paired studies and
      AMM in the whole cohort. RESULTS: Annulus LAD was measured using AMM, in all
      cases and segments, irrespective of cardiac axis alignment to the ultrasound
      beam. Good correlation existed between AMM and MM (RV r = 0.901, LV r = 0.899,
      IVS r = 0.815, p < 0.001). AMM recorded higher LAD values than MM in RV [mean
      6.17 (SD 1.46) vs. 5.82 (SD 1.74) mm, p = 0.002] and LV [mean 4.18 (SD 1.11) vs.
      3.98 (SD 1.12), p = 0.007]. Both methods showed LAD in RV > LV > IVS and a
      significant gestational increase in LAD values in all segments (p < 0.001)
      CONCLUSIONS: AMM permits offline evaluation of fetal longitudinal myocardial
      function in routinely obtained 2D fetal heart images with similar values to
      conventional MM in paired studies recorded <30 degrees .

PMID- 22613841
TI  - A simple optogenetic system for behavioral analysis of freely moving small
      animals.
AB  - We present a new and simple optogenetic system for the behavioral analysis of
      small animals. This system includes a strong LED ring array, a high-resolution
      CCD camera, and the improved channelrhodopsin ChRGR. We used the system for
      behavioral analysis with the nematode Caenorhabditis elegans as a model, and we
      found that it can stimulate ChRGR expressed in the body wall muscles of the
      animals to modulate the behavior. Our results indicate that this system may be
      suitable for optogenetic behavioral analysis of freely moving small animals under
      various conditions to understand the principles underlying brain functions.

PMID- 22613844
TI  - Genetic variability of Xrcc3 and Rad51 modulates the risk of head and neck
      cancer.
AB  - A case-control study was conducted to analyze the possible associations between
      the head and neck cancer (HNC) risk and fourteen single nucleotide polymorphisms
      (SNPs) and haplotypes in Xrcc3 and Rad51 genes. This study involved 81 HNC cases
      and 111 healthy control subjects. A significant risk-increasing effect of
      rs3212057 (p.Arg94His) SNP in Xrcc3 (OR=6.6; p<0.01) was observed. On the other
      hand, risk-decreasing effect was found for rs5030789 (g.3997A>G) and rs1801321
      (c.-60G>T) in 5' near gene and 5'UTR regions of Rad51, respectively (OR=0.3 and
      OR=0.2, p<0.05, respectively). Moreover, these effects were shown to be modulated
      by tobacco-smoking status and gene-gene interactions. Concluding, the genetic
      variability of Xrcc3 and/or Rad51 genes might be of relevance with respect to HNC
      risk.

PMID- 22613845
TI  - Interplay between two myogenesis-related proteins: TBP-interacting protein 120B
      and MyoD.
AB  - Gene expression in myogenesis is governed by multiple myogenic factors including
      MyoD. Previously, we demonstrated that TBP-interacting protein 120B (TIP120B)
      promotes in vitro myogenesis through its anti-ubiquitination ability. In this
      study, we investigated interplay between MyoD and TIP120B. Mouse C2C12 cells
      subjected to myotube differentiation contained increased amounts of TIP120B and
      MyoD. Dexamethasone, which inhibits myogenic signaling, decreased the amounts of
      those proteins. Mouse and human TIP120B promoters, which carry multiple E-box
      motifs, were potentiated by MyoD. In the human TIP120B, a proximal E-box binds to
      MyoD in vitro and exhibits MyoD-dependent transcription activation function.
      Expression of the endogenous TIP120B gene was correlated with the level of MyoD
      in different types of muscle-related cells. Furthermore, MyoD binds specifically
      to a proximal E-box-carrying promoter region in chromatin. Proteasome-sensitive
      MyoD was increased and decreased by overexpression and knockdown of TIP120B,
      respectively. Moreover, stability of MyoD was increased by TIP120B. The results
      suggest that MyoD and TIP120B potentiate each other at gene expression and post
      translation levels, respectively, which may promote myogenesis cooperatively.

PMID- 22613846
TI  - Phylogenetic reconstruction at the species and intraspecies levels in the genus
      Pisum (L.) (peas) using a histone H1 gene.
AB  - A phylogenetic analysis of the genus Pisum (peas), embracing diverse wild and
      cultivated forms, which evoke problems with species delimitation, was carried out
      based on a gene coding for histone H1, a protein that has a long and variable
      functional C-terminal domain. Phylogenetic trees were reconstructed on the basis
      of the coding sequence of the gene His5 of H1 subtype 5 in 65 pea accessions.
      Early separation of a clear-cut wild species Pisum fulvum is well supported,
      while cultivated species Pisum abyssinicum appears as a small branch within Pisum
      sativum. Another robust branch within P. sativum includes some wild and almost
      all cultivated representatives of P. sativum. Other wild representatives form
      diverse but rather subtle branches. In a subset of accessions, PsbA-trnH
      chloroplast intergenic spacer was also analysed and found less informative than
      His5. A number of accessions of cultivated peas from remote regions have a His5
      allele of identical sequence, encoding an electrophoretically slow protein
      product, which earlier attracted attention as likely positively selected in harsh
      climate conditions. In PsbA-trnH, a 8bp deletion was found, which marks
      cultivated representatives of P. sativum.

PMID- 22613842
TI  - Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration
      with mRNA expression.
AB  - Lung cancer is the leading cause of cancer death worldwide, and adenocarcinoma is
      its most common histological subtype. Clinical and molecular evidence indicates
      that lung adenocarcinoma is a heterogeneous disease, which has important
      implications for treatment. Here we performed genome-scale DNA methylation
      profiling using the Illumina Infinium HumanMethylation27 platform on 59 matched
      lung adenocarcinoma/non-tumor lung pairs, with genome-scale verification on an
      independent set of tissues. We identified 766 genes showing altered DNA
      methylation between tumors and non-tumor lung. By integrating DNA methylation and
      mRNA expression data, we identified 164 hypermethylated genes showing concurrent
      down-regulation, and 57 hypomethylated genes showing increased expression.
      Integrated pathways analysis indicates that these genes are involved in cell
      differentiation, epithelial to mesenchymal transition, RAS and WNT signaling
      pathways, and cell cycle regulation, among others. Comparison of DNA methylation
      profiles between lung adenocarcinomas of current and never-smokers showed modest
      differences, identifying only LGALS4 as significantly hypermethylated and down
      regulated in smokers. LGALS4, encoding a galactoside-binding protein involved in
      cell-cell and cell-matrix interactions, was recently shown to be a tumor
      suppressor in colorectal cancer. Unsupervised analysis of the DNA methylation
      data identified two tumor subgroups, one of which showed increased DNA
      methylation and was significantly associated with KRAS mutation and to a lesser
      extent, with smoking. Our analysis lays the groundwork for further molecular
      studies of lung adenocarcinoma by identifying novel epigenetically deregulated
      genes potentially involved in lung adenocarcinoma development/progression, and by
      describing an epigenetic subgroup of lung adenocarcinoma associated with
      characteristic molecular alterations.

PMID- 22613847
TI  - The significant increase of FcgammaRIIIA (CD16), a sensitive marker, in patients
      with coronary heart disease.
AB  - Our previous studies suggest that Fc receptor III A of immunoglobulin G
      (FcgammaRIIIA, also named CD16) is closely correlated to coronary heart disease
      (CHD). However, whether or not deregulated FcgammaRIIIA expression is involved in
      the development of CHD remains largely unclear. Herein, we investigated the
      FcgammaRIIIA mRNA expression in the leukocytes, the serum protein level of
      soluble CD16 (sCD16) and membrane CD16 on monocytes from 100 diagnosed CHD
      patients and 40 healthy individuals. Our results demonstrated that there was a
      significant increase of FcgammaRIIIA at the mRNA level in leukocytes, and at the
      protein level for both sCD16 in sera and membrane CD16 on monocytes from CHD
      patients compared to the healthy control. Similarly to the soluble CD14 (sCD14),
      the level of macrophage colony stimulating factor (M-CSF) in sera was also higher
      in CHD patients than that in the control individuals. Furthermore, the levels of
      inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-1 (IL-1), in sera and the mean fluorescent intensity of intercellular
      adhesion molecule 1 (ICAM-1, CD54) on CD14(+) CD16(+) monocytes were increased in
      CHD patients. Overall, these data demonstrated that FcgammaRIIIA (CD16) is
      involved in the pathogenesis of CHD by activating monocytes and stimulating
      inflammation. The significant increase of CD14(+) CD16(+) monocytes in CHD
      patients therefore suggested that the increase of the FcgammaRIIIA level might be
      a sensitive marker for the CHD diagnosis.

PMID- 22613848
TI  - Evidence of association between interferon regulatory factor 5 gene polymorphisms
      and asthma.
AB  - Asthma is a heterogeneous disorder hallmarked by chronic inflammation in the
      respiratory system. Exacerbations of asthma are correlated with respiratory
      infections. Considering the implication of interferon regulatory factor 5 (IRF5)
      in innate and adaptive immunity, we investigated the preferential transmission
      patterns of ten IRF5 gene polymorphisms in two asthmatic family cohorts. A common
      IRF5 haplotype was found to be associated with asthma and the severity of
      asthmatic symptoms. Stratified analysis of subgroups of asthmatic individuals
      revealed that the associations were more pronounced in nonatopic asthmatic
      individuals. In addition, the risk alleles of IRF5 polymorphisms for asthma were
      almost completely opposite to those for autoimmune disorders. Our study provides
      the first evidence of association between IRF5 and asthma, and sheds light on the
      related but potentially distinct roles of IRF5 alleles in the pathogenesis of
      asthma and autoimmune disorders.

PMID- 22613849
TI  - Expression of aromatase and estrogen receptor alpha in chondrosarcoma, but no
      beneficial effect of inhibiting estrogen signaling both in vitro and in vivo.
AB  - BACKGROUND: Chondrosarcomas are malignant cartilage-forming tumors which are
      highly resistant to conventional chemotherapy and radiotherapy. Estrogen
      signaling is known to play an important role in proliferation and differentiation
      of chondrocytes and in growth plate regulation at puberty. Our experiments focus
      on unraveling the role of estrogen signaling in the regulation of neoplastic
      cartilage growth and on interference with estrogen signaling in chondrosarcomas
      in vitro and in vivo. METHODS: We investigated the protein expression of estrogen
      receptor alpha (ESR1), androgen receptor (AR), and aromatase in tumor specimens
      of various chondrosarcoma subtypes, and (primary) chondrosarcoma cultures. Dose
      response curves were generated of conventional central chondrosarcoma cell lines
      cultured in the presence of 17-beta-estradiol, dihydrotestosterone, 4-androstene
      3,17dione, 4-hydroxytamoxifen, fulvestrant and aromatase inhibitors. In a pilot
      series, the effect of anastrozole (n=4) or exemestane (n=2) treatment in 6
      chondrosarcoma patients with progressive disease was explored. RESULTS: We showed
      protein expression of ESR1 and aromatase in a large majority of all subtypes.
      Only a minority of the tumors showed few AR positive cells. The dose-response
      assays showed no effect of any of the compounds on proliferation of conventional
      chondrosarcoma in vitro. The median progression-free survival of the patients
      treated with aromatase inhibitors did not significantly deviate from untreated
      patients. CONCLUSIONS: The presence of ESR1 and aromatase in chondrosarcoma
      tumors and primary cultures supports a possible role of estrogen signaling in
      chondrosarcoma proliferation. However, our in vitro and pilot in vivo studies
      have shown no effect of estrogen-signaling inhibition on tumor growth.

PMID- 22613850
TI  - Epidemiology of cutaneous adverse drug reactions.
AB  - Epidemiologic investigations of cutaneous adverse drug reactions (cADR) are
      important to evaluate their impact in dermatology and health care in general as
      well as their burden for affected patients. Few epidemiologic studies have been
      performed on frequent non-life-threatening cADR including reactions of both
      delayed and immediate hypersensitivity, such as maculopapular exanthema, fixed
      drug eruption and urticaria. Concerning rare but life-threatening severe
      cutaneous adverse reactions, e.g. toxic epidermal necrolysis (TEN), Stevens
      Johnson syndrome (SJS), acute generalized exanthematous pustulosis and drug
      reaction with eosinophilia and systemic symptoms, several epidemiologic studies
      have been performed to date, some of which are still ongoing. Such studies
      enabled the calculation of reliable incidence rates and demographic data, but
      also allowed to perform risk estimation for drugs. The spectrum of drugs causing
      cADR differs substantially when separating the various clinical conditions.
      Whereas antibiotics are by far the most frequent inducers of milder cADR like
      maculopapular exanthema, they have a much lower risk to induce SJS/TEN, for which
      high-risk drugs are anti-infective sulfonamides, allopurinol, certain anti
      epileptic drugs, nevirapine and nonsteroidal anti-inflammatory drugs (NSAIDS) of
      the oxicam type. In contrast, acute generalized exanthematous pustulosis is
      predominantly caused by the antibiotics pristinamycin and aminopenicillins,
      followed by quinolones, (hydroxy-)chloroquine and sulfonamides. Drug reaction
      with eosinophilia and systemic symptoms can be induced by a number of drugs known
      to cause SJS/TEN, such as certain antiepileptics and allopurinol, but also other
      medications (e.g. minocyclin).

PMID- 22613851
TI  - Genetics and the potential for predictive tests in adverse drug reactions.
AB  - Drug hypersensitivity reactions are an immune-mediated reaction to otherwise
      innocuous antigens derived from drugs. These reactions can affect many different
      organs, with the skin being the commonest. Skin involvement can range in severity
      with hypersensitivity syndrome (or DRESS) and the blistering reactions (Stevens
      Johnson syndrome, toxic epidermal necrolysis), also termed serious cutaneous
      adverse drug reactions, being the most severe and most feared. There is
      increasing evidence for the role of the immune system in the pathogenesis of
      these reactions, with drug-specific T cells having been identified in many
      patients. Until recently, very little was known about the predisposition to these
      reactions. However, the availability of more accurate molecular typing methods,
      and the ability to analyse the whole genome in an unbiased fashion, has led to
      some remarkable findings of the role of the HLA genes as genomic biomarkers of
      predisposition. The 'revolution' started with abacavir where the predisposition
      to hypersensitivity was linked to HLA-B*57:01, which was confirmed in a clinical
      trial, and where its implementation has shown to reduce the incidence of
      hypersensitivity in a cost-effective manner. Since then, associations have also
      been shown for allopurinol (HLA-B*58:01)- and carbamazepine (HLA-B*1502 and HLA
      A*3101)-induced serious cutaneous adverse drug reactions. The latter is
      interesting since the association with HLA-B*1502 is present in certain South
      Eastern Asian populations, and the predisposition is phenotype specific (only for
      SJS/TEN). The utility of this biomarker has been shown in a prospective cohort
      study performed in Taiwan. By contrast, the association with HLA-A*3101 is seen
      in more diverse ethnic groups, and predisposes to mild as well more severe
      cutaneous reactions associated with carbamazepine. It is important to note that
      strong HLA associations have also been shown with a number of drugs that cause
      liver injury including flucloxacillin, lumiracoxib, lapatinib and ximelagatran,
      indicating that the immune system is also important in the pathogenesis of other
      forms of drug-induced organ toxicity. The crucial question as to whether these
      HLA alleles are truly causative or acting as surrogate markers of predisposition,
      however, is still unclear, and will require further investigations in larger
      patient cohorts, through the use of bioinformatic techniques, fine mapping using
      next generation sequencing technologies and functional studies.

PMID- 22613852
TI  - Etiology and pathogenesis of adverse drug reactions.
AB  - In clinical routine, adverse drug reactions (ADR) are common, and they should be
      included in the differential diagnosis in all patients undergoing drug treatment.
      Only part of those ADR are immune-mediated hypersensitivity reactions and thus
      true drug allergies. Far more common are non-immune-mediated ADR, e.g. due to the
      pharmacological properties of the drug or to the individual predisposition of the
      patient (enzymopathies, cytokine dysbalance, mast cell hyperreactivity). In true
      drug allergiesT cell- and immunoglobulin E (lgE)-mediated reactions dominate the
      clinical presentation. T cell-mediated ADR usually have a delayed appearance and
      include skin eruptions in most cases. Nevertheless, it should not be forgotten
      that they may involve systemic T cell activation and thus take a severe,
      sometimes lethal turn. Clinical danger signs are involvement of mucosal surfaces,
      blistering within the exanthematous skin areas and systemic symptoms, e.g. fever
      or malaise. Drug presentation via antigen-presenting cells to T cells can either
      involve the classical pathway of haptenization of endogenous proteins or be
      directly mediated via noncovalent binding to immune receptors (MHC molecules or T
      cell receptors), the so-called p-i concept. Flare-up reactions during the acute
      phase of T cell-mediated ADR should not be mistaken for true drug allergies, as
      they only occur in the setting of a highly activated T cell pool. IgE-mediated
      ADR are less frequent and involve mast cells and/or basophils as peripheral
      effector cells. Recent data suggest that certain patients with drug allergy have
      a preexistent sensitization although they have never been exposed to the culprit
      drug, probably due to cross-reactivity. Thus, allergic drug reactions on first
      encounter are possible. In general, the extent of cross-reactivity is higher in
      IgE-compared to T cell-mediated ADR. Based on a specific ethnic background and
      only for severe T cell-mediated ADR to certain drugs, a strong HLA association
      has been established recently.

PMID- 22613853
TI  - Diagnostic approach to drug allergy.
AB  - The approach to drug hypersensitivity always comprises a clinical and a
      diagnostic workup. About 15% of drug side effects are due to hypersensitivity
      reactions. All types of immunological reactions can be induced by drugs, but type
      I and type IV reactions are seen most often. The initial judgment of the skin
      symptoms is therefore one of the key factors besides a stringent history of drug
      intake for a further diagnostic workup. The goal of a diagnostic workup is not
      only to identify the culprit drug, but also to defer the patient from similar
      drugs in order to prevent a second episode. In the case of missing alternatives
      and unidentified drug sensitivity, reexposure to the previous drug must be
      discussed; however, in severe cutaneous reactions this should generally be
      avoided.

PMID- 22613854
TI  - Histopathological patterns indicative of distinct adverse drug reactions.
AB  - Histologically, drug eruptions may present virtually all patterns of inflammation
      in the skin, including spongiotic, lichenoid and psoriasiform dermatitis as well
      as vasculitis or panniculitis. Drug reactions may mimic specific skin diseases
      such as lupus erythematosus, lichen planus or lymphoma. While a single drug may
      cause a wide range of reaction patterns, no reaction pattern is specific for a
      certain drug. Nevertheless, some reactions are quite characteristic for certain
      drugs as for example psoriasiform dermatitis for anti-TNF agents or folliculitis
      for epidermal growth factor receptor antagonists. Heightened awareness to the
      possible mimicry of other skin diseases as well as integration of clinical data
      is pivotal for the appropriate histological diagnosis of drug reactions in the
      skin. For practical reasons and in the aim of helping clinicians, the different
      drug reactions described in this chapter are classified according to the main
      histological reaction pattern present. Nevertheless, this classification may be
      somewhat artificial in some cases as drug reactions often reveal a coexistence of
      different reaction patterns.

PMID- 22613855
TI  - Uncomplicated drug-induced disseminated exanthemas.
AB  - Exanthematous reactions with various morphological and localization patterns are
      the most frequently encountered adverse drug reactions involving the skin. The
      time course of benign exanthemas typically encompasses a few days to some weeks.
      They are not complicated by severe systemic symptoms or internal organ
      involvement. They manifest themselves in a polymorphous manner with primary
      efflorescences including macules, papules, and more rarely limited pustules,
      vesicles or bullae, followed by secondary lesions such as scales, and more rarely
      erosions and hemorrhage. Due to the limited inflammatory reaction pattern of the
      skin, these exanthemas may mimic other discrete skin disorders and infectious
      exanthemas. Rarely, typical skin disorders such as lichen planus or psoriasis are
      imitated or inflammatory reaction patterns such as Sweet's syndrome and erythema
      nodosum are observed. The most common groups of eliciting drugs include
      antibiotics, antiinfectious drugs, tuberculostatic drugs, anticonvulsant and
      antihypertensive agents. On the other hand, there are some drugs that have been
      very rarely associated with an adverse cutaneous reaction. Immunological effector
      mechanisms often include T cells and various chemokines and cytokines. Diagnosis
      is based on a detailed history, an exact morphological diagnosis and an accurate
      evaluation of the chronology. Histology may support the clinical diagnosis. After
      complete healing and within an interval of 6 weeks to 6 months, diagnostic skin
      and some in vitro tests are recommended. The treatment includes early withdrawal
      of the suspected culprit drugs, application of topical corticosteroids, systemic
      antihistamines and, if necessary, systemic corticosteroids.

PMID- 22613856
TI  - Drug-induced angioedema.
AB  - Angioedema (AE) is the end result of deep dermal, subcutaneous and/or submucosal
      swelling, and represents a major criterion in the definition of anaphylaxis. Drug
      induced AE, like other cutaneous drug reactions, is most frequently elicited by
      betalactam antibiotics and nonsteroidal antiinflammatory drugs. However,
      differences exist in their underlying pathophysiology (IgE mediated vs.
      pseudoallergic). Blockers of the renin-angiotensin-aldosterone system are the
      most common class of medications associated with isolated AE and are most
      probably related to elevated bradykinin levels. Typically, ACE inhibitor
      associated AE can occur up to several years after initiating treatment, and may
      sporadically recur even after discontinuation. A comprehensive investigation of
      AE must include analysis of complement factors, tryptase levels as well as
      specific allergy tests. Furthermore, other possible causative agents ought to be
      excluded. Every patient with drug-induced AE must receive an allergy pass as well
      as emergency medication including epinephrine. In some cases, inhibitors of the
      bradykinin system may be considered for treatment.

PMID- 22613857
TI  - Fixed drug eruption: the dark side of activation of intraepidermal CD8+ T cells
      uniquely specialized to mediate protective immunity.
AB  - Fixed drug eruption (FDE) is generally regarded as representing the mild end of
      drug-induced dermatitis, but the clinical importance of recognizing this disease
      as an abortive, localized variant of toxic epidermal necrolysis has received
      increasing attention in recent years. FDE often presents with a wide spectrum of
      clinical manifestations indistinguishable from those of other skin diseases, such
      as erythema multiforme, Stevens-Johnson syndrome /toxic epidermal necrolysis,
      cellulitis, paronychia, lichen planus, and parapsoriasis en plaques. These
      unusual forms of FDE are likely to be overlooked unless the possibility of a drug
      etiology is routinely considered in the differential diagnosis of any patient
      with these diseases. Clinical awareness and recognition of these unique forms are
      essential for avoiding a misdiagnosis. Intraepidermal CD8+ T cells resident in
      the FDE lesions that have the capacity to rapidly produce large amounts of IFN
      gamma are likely to have a key role in mediating localized epidermal injury,
      while they may represent a T cell subset uniquely specialized to mediate
      protective immunity against various pathogens.

PMID- 22613858
TI  - Drug-induced hypersensitivity syndrome: recent advances in the diagnosis,
      pathogenesis and management.
AB  - Drug-induced hypersensitivity syndrome (DIHS), also referred to as drug reaction
      with eosinophilia with systemic symptoms, is a life-threatening multiorgan system
      reaction caused by a limited number of drugs such as anticonvulsants. This
      syndrome is characterized by fever, rash, lymphadenopathy, hepatitis, and
      leukocytosis with eosinophilia. DIHS has several unique features that include the
      delayed onset, paradoxical deterioration of clinical symptoms after withdrawal of
      the causative drug and unexplained cross-reactivity to multiple drugs with
      different structures. Because of these features and a lack of awareness of this
      syndrome, DIHS is undoubtedly underdiagnosed in many countries despite its
      worldwide distribution. The clinical variability in the presentation and course
      of clinical symptoms of DIHS could now be interpreted as an indication that
      several herpesviruses reactivate in a sequential manner independently in the
      different organs. Dramatic expansions of functional regulatory T (Treg) cells
      observed in the acute stage would serve to induce such sequential reactivations
      of herpesviruses while a gradual loss of Treg function occurring after resolution
      of DIHS could increase the risk of subsequently developing autoimmune disease.
      Although systemic corticosteroids are the mainstay of treatment, it remains to be
      determined whether this treatment is beneficial from a viewpoint of disease
      outcome and sequelae.

PMID- 22613859
TI  - Acute generalized exanthematous pustulosis.
AB  - The key clinical features of acute generalized exanthematous pustulosis (AGEP)
      are the acute occurrence of numerous pinhead-sized nonfollicular sterile pustules
      on an edematous erythema accompanied by fever and leukocytosis. Histology shows
      mainly spongiform subcorneal and/or intraepidermal pustules, frequently a marked
      edema of the papillary dermis, neutrophils, and often eosinophils. AGEP is a
      reaction pattern mostly caused by drugs, the ones with the highest risk being
      antibacterial agents like ampicillin/amoxicillin, and quinolones, pristinamycin,
      anti-infective sulfonamides, the antimycotic drug terbinafine,
      (hydroxy)chloroquine, and diltiazem. In addition, a large number of other drugs
      as well as infections have been reported as triggers. AGEP is an acute and
      sometimes severe reaction. When the causative agent is withdrawn, it usually
      resolves quickly without specific treatment.

PMID- 22613860
TI  - Stevens-Johnson syndrome and toxic epidermal necrolysis.
AB  - Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are rare but
      severe adverse cutaneous drug reactions that are to be considered medical
      emergencies. The average reported mortality rate for SJS is 1-5%, and up to 25
      35% for TEN. TEN and SJS are characterized by more or less extensive painful
      erythematous and erosive lesions of the skin, conjunctiva and mucous membranes
      resulting from massive apoptosis of epithelial cells, and are considered to be
      two ends of a spectrum of severe epidermolytic adverse cutaneous drug reactions,
      differing only by their extent of skin detachment. Drugs including allopurinol,
      antibiotics, anticonvulsants and NSAIDs of the oxicam type are the main cause of
      SJS/TEN in most cases. Recent evidence supports a genetic susceptibility to SJS
      and TEN as exemplified by the strong association observed in Han Chinese between
      the human leukocyte antigen HLA-B*1502, and SJS induced by carbamazepine.
      Diagnosis relies mainly on clinical signs together with the histological analysis
      of a skin biopsy showing typical full-thickness epidermal necrolysis due to
      extensive keratinocyte apoptosis. Differential diagnoses include autoimmune
      bullous dermatoses, acute generalized exanthematous pustulosis, disseminated
      fixed bullous drug eruption and staphyloccocal scalded skin syndrome. Due to the
      high risk of mortality, management of patients with SJS/TEN requires rapid
      diagnosis, evaluation of the prognosis using SCORTEN, rapid identification and
      interruption of the culprit drug, specialized supportive care ideally in an
      intensive care unit, and the consideration of immunomodulatory agents such as
      high-dose intravenous immunoglobulin.

PMID- 22613861
TI  - Phototoxic and photoallergic cutaneous drug reactions.
AB  - A variety of topical and systemic drugs can induce cutaneous photosensitive
      reactions. These drugs and their metabolites accumulate in the skin and increase
      photosensitivity of the skin typically in the UVA spectrum of light. Concerning
      the underlying biochemical mechanisms and the phenotype of reactions,
      photosensitivity can be divided into phototoxic and photoallergic reactions. In
      phototoxic reactions, often highly reactive oxygen molecules are formed that
      induce tissue damage. Skin changes resemble sunburn and develop within hours
      after incubation with the drug together with sunlight. In contrast, photoallergic
      reactions are type IV hypersensitivity reactions, and therefore resemble eczema.
      They usually develop within days and are less common than phototoxic reactions.
      Diagnosis is based on a synopsis of complete history, clinical examination,
      phototesting for minimal phototoxicity dose, patch testing including photopatch
      tests, and histopathology. Mainstays of treatment are the withdrawal of the
      culprit drug, and avoidance of sunlight by wearing protective clothing and
      broadband sunscreens with UVA filters.

PMID- 22613862
TI  - Immediate and delayed cutaneous reactions to radiocontrast media.
AB  - Hypersensitivity reactions to contrast media (CM) are frequent causes of
      anaphylaxis and drug exanthemas. Adverse events after CM exposure are classified
      into immediate (<=1 h) and non-immediate reactions (>1 h), with differing
      mechanisms. In the majority of patients with immediate reactions, IgE-mediated
      allergy cannot be demonstrated, and the underlying mechanism remains unknown.
      However, recent data have provided evidence for skin test positivity and/or
      specific IgE in some patients. T cell-mediated hypersensitivity is the
      responsible mechanism for the majority of non-immediate skin eruptions. These
      insights have consequences for diagnosis and prevention. Skin testing evolves to
      be a useful tool for diagnosis of CM allergy. Skin tests have been employed to
      confirm this hypersensitivity. Previous reactors have an increased risk to
      develop new reactions upon repeated exposure; however, other risk factors are
      poorly defined. The use of skin tests for the selection of a 'safe' CM is under
      investigation with promising results. In vitro tests to search for CM-specific
      cell activation include flow cytometric approaches, lymphocyte cultures and
      construction of cell lines and hybridomas. Premedication of previous reactors is
      common practice among radiologists; however, breakthrough reactions are a
      concern, and physicians should not rely on the efficacy of pharmacological
      premedication.

PMID- 22613863
TI  - Cutaneous drug eruptions associated with the use of new oncological drugs.
AB  - There is a variety of adverse effects and toxicities of newer and older
      chemotherapeutic agents which emerge in the skin, mucosa and adnexa. Common skin
      reactions while undergoing chemotherapy include alopecia, changes in skin
      pigmentation, palmoplantar erythrodysesthesia, nail dystrophies and stomatitis.
      Extravasation injuries or hypersensitivity reactions may be severe. New oncologic
      agents have led to the development of different, class-specific cutaneous side
      effects. Epidermal growth factor receptor (EGFR) inhibitors induce papulopustular
      rashes in a high percentage of patients as well as, to a smaller degree, xerosis
      cutis, hair and nail changes, hyper pigmentation and enhancement of radiation
      dermatitis. Multikinase inhibitors will often cause hand-foot syndrome, but may
      also induce facial erythema, subungual splinter hemorrhages and other less
      frequent skin changes. BRAF inhibitors can lead to rash and development of
      cutaneous keratinocytic neoplasias for which patients should be closely
      monitored. Finally, MEK/ERK inhibitors induce similar skin toxicities to EGFR
      inhibitors such as papulopustular rashes, xerosis cutis and paronychia. Our
      chapter will focus on the clinical picture, histopathology and treatment options
      of these new class-specific cutaneous side effects.

PMID- 22613864
TI  - Cutaneous drug eruptions associated with the use of biologies and cutaneous drug
      eruptions mimicking specific skin diseases.
AB  - Drug eruptions are common adverse events affecting approximately 3% of
      hospitalized patients, and can be seen with the use of almost any medication.
      Making a diagnosis could be challenging because no pattern is specific for a
      particular drug. A study of clinical aspects, histopathology and history of drug
      intake is usually necessary to establish the diagnosis, and discontinue the
      offending agent when feasible. The pathomechanisms of drug-related skin reactions
      remain unclear. However, the induction of drug reactions by a new class of
      biologies which block a specific target should help to better understand the
      pathogenesis of these eruptions.

PMID- 22613865
TI  - Desensitization for hypersensitivity reactions to medications.
AB  - Rapid drug desensitization (RDD) is a technique that induces temporary tolerance
      to a drug, allowing a medication-allergic patient to receive the optimal agent
      for his or her disease. Through RDD, patients with IgE and non-IgE
      hypersensitivity reactions (HSRs) including anaphylaxis can safely be
      administered important medications while minimizing or completely inhibiting
      adverse reactions. Adverse reactions to drugs are increasingly recognized as
      important contributors to disease as well as impediments to the best treatment of
      dermatological, infectious, autoimmune, and neoplastic disorders. With the
      development of novel pharmacologic agents and the evolution of personalized
      treatments based on pharmacogenetic profiling, clinicians must decide which agent
      is the best for a particular patient with a given disease. Biological agents have
      greatly improved the treatment of chronic inflammatory diseases and malignancies
      while limiting some medication-associated toxicities. Because of better outcomes,
      longer patient survival, and extended treatment courses, patients are exposed to
      drugs more frequently and for longer time periods, increasing the risk of
      sensitization and the potential for HSRs. The frequency of adverse drug reactions
      has therefore increased in the last 10 years. Because of the severity of some
      reactions and the fear of inducing a potentially lethal reaction in highly
      sensitized patients, first-line treatments are sometimes abandoned, relegating
      hypersensitive patients to secondary, less effective, therapy. Some of these
      reactions are mast cell-mediated HSRs, a subset of which occur through an IgE
      dependent mechanism, and are thus true allergies. Others involve mast cells, but
      an IgE mechanism cannot be demonstrated. Both types of reactions are amenable to
      RDD, and our group has successfully performed several hundred desensitizations to
      chemotherapy, antibiotics and biological agents including monoclonal antibodies
      with a standardized 12-step protocol that can be universally applied to all
      desensitizations. The molecular basis of RDD has now been studied, and an in
      vitro mouse mast cell model has shown that RDD is an antigen-specific process
      that does not induce subclinical mast cell mediator release, and that blocks the
      release of acute and late mast cell mediators by preventing calcium influx and
      antigen/IgE/and IgE receptor internalization.

PMID- 22613866
TI  - Constrained evolution drives limited influenza diversity.
AB  - H3N2 influenza A viruses have been widely circulating in human populations since
      the pandemic of 1968. A striking feature of the evolutionary development of this
      strain has been its 'canalized' nature, with narrow evolutionary trees dominated
      by long trunks with few branching, or bifurcation events and a consequent lack of
      standing diversity at any single point. This is puzzling, as one might expect
      that the strong human immune response against the virus would create an
      environment encouraging more diversity, not less. Previous models have used
      various assumptions in order to account for this finding. A new analysis
      published in BMC Biology suggests that this processive evolution down a single
      path can be recapitulated by a relatively simple model incorporating only two
      primary parameters - the mutation rate of the virus, and the immunological
      distance created by each mutation - so long as these parameters are within a
      particular narrow but biologically plausible range.

PMID- 22613867
TI  - Living with the loss of a child: mothers in the criminal justice system.
AB  - OBJECTIVE: Bereaved mothers have expressed the need to maintain a bond with their
      children who have died, to retain control over the funeral rituals, and to
      express their loss to others who are empathetic. This study describes grief over
      the loss of a child in women who have been or are currently incarcerated, and the
      influence of the women's family members. METHOD: This descriptive qualitative
      study consisted of open-ended interview questions to encourage the women to
      describe their experience in their own words. A purposive sample (N = 10) was
      recruited from a prison re-entry program and a county jail. RESULTS: All of the
      participants described maladaptive responses such as the use of alcohol and
      drugs, restricted family support, and dysfunctional coping. None of the
      participants had received focused bereavement services. SIGNIFICANCE OF RESULTS:
      The descriptive perspective from the participants can inform clinicians who work
      with women who have a history of involvement with the criminal justice system,
      and recommends that they should inquire about the women's children and
      experiences with loss. Community re-entry and jail/prison counselors should
      provide access to confidential and group-based therapeutic support, including
      Compassionate Friends.

PMID- 22613868
TI  - Albumin-induced epithelial mesenchymal transformation.
AB  - BACKGROUND: Progressive chronic kidney disease is often associated with
      albuminuria and renal fibrosis linked to the accumulation of myofibroblasts
      producing extracellular matrix. Renal myofibroblasts are derived from a number of
      cells including tubular epithelial cells (TECs) through epithelial mesenchymal
      transformation (EMT). This study explores the hypothesis that exposure of TECs to
      albumin induces EMT. METHODS: Normal rat TECs (NRK52E) were exposed in culture to
      de-lipidated bovine serum albumin (dBSA; 10 mg/ml) for 2, 4 and 6 days.
      Binding/uptake of fluoresceined albumin by PTCs was evaluated. Transformation
      into myofibroblasts was assessed by light and electron microscopy,
      immunofluorescence and Western blotting for alpha-smooth muscle actin (alpha
      SMA), E-cadherin and transforming growth factor-beta1 (TGF-beta1). We also
      investigated the expression of fibroblast-specific protein-1 (FSP-1) and
      collagens I, III and IV. TGF-beta1 biological activity, mRNA and protein were
      measured. A neutralising anti-TGF-beta1 antibody was used to analyse the role of
      TGF-beta1 in albumin-induced EMT. RESULTS: Exposure of TECs to dBSA led to
      binding/uptake of albumin as well as fibroblastic morphological changes.
      Incubation of TECs with dBSA caused a reduction of TEC marker E-cadherin (ANOVA p
      = 0.0002) and de novo expression of fibroblast markers alpha-SMA and FSP-1 (ANOVA
      p = 0.0001) in a time-dependent manner. It also increased expression and activity
      of TGF-beta1. Neutralisation of TGF-beta1 significantly reduced EMT (p < 0.01).
      CONCLUSION: This study demonstrates that in vitro, albumin induces the
      transformation of TECs into cells with myofibroblast characteristics; a process
      that may be TGF-beta1 dependent.

PMID- 22613869
TI  - Target mimics: an embedded layer of microRNA-involved gene regulatory networks in
      plants.
AB  - BACKGROUND: MicroRNAs (miRNAs) play an essential role in gene regulation in
      plants. At the same time, the expression of miRNA genes is also tightly
      controlled. Recently, a novel mechanism called "target mimicry" was discovered,
      providing another layer for modulating miRNA activities. However, except for the
      artificial target mimics manipulated for functional studies on certain miRNA
      genes, only one example, IPS1 (Induced by Phosphate Starvation 1)-miR399 was
      experimentally confirmed in planta. To date, few analyses for comprehensive
      identification of natural target mimics have been performed in plants. Thus,
      limited evidences are available to provide detailed information for interrogating
      the questionable issue whether target mimicry was widespread in planta, and
      implicated in certain biological processes. RESULTS: In this study, genome-wide
      computational prediction of endogenous miRNA mimics was performed in Arabidopsis
      and rice, and dozens of target mimics were identified. In contrast to a recent
      report, the densities of target mimic sites were found to be much higher within
      the untranslated regions (UTRs) when compared to those within the coding
      sequences (CDSs) in both plants. Some novel sequence characteristics were
      observed for the miRNAs that were potentially regulated by the target mimics. GO
      (Gene Ontology) term enrichment analysis revealed some functional insights into
      the predicted mimics. After degradome sequencing data-based identification of
      miRNA targets, the regulatory networks constituted by target mimics, miRNAs and
      their downstream targets were constructed, and some intriguing subnetworks were
      further exploited. CONCLUSIONS: These results together suggest that target
      mimicry may be widely implicated in regulating miRNA activities in planta, and we
      hope this study could expand the current understanding of miRNA-involved
      regulatory networks.

PMID- 22613870
TI  - Mechanisms leading to the formation of micronuclei containing sex chromosomes
      differ with age.
AB  - The frequency of spontaneously occurring micronuclei (MN) increases with age,
      with many of these MN containing sex chromatin. However, it is not known if this
      MN frequency increase is attributable to a higher number of the same cellular
      events that occur in younger people, or if a different sex chromosomal
      instability mechanism(s) arises with age. To gain insight regarding this
      question, the total number of signals present in MN and their corresponding
      binucleates, was scored in older (ages 40-80+ y.o.; n=40) compared to younger (7
      39 y.o.; n=19) individuals using probes specific for the X and Y chromosomes. In
      19.9% of the cells scored at least one sex chromatin positive micronucleus was
      present. A significant decrease in cells having a "corrective" loss pattern (i.e.
      trisomy rescue, leading to euploid binucleates following sex chromatin exclusion
      into the MN) was observed with increasing age for the Y chromosome in males
      (p=0.022) and the X chromosome in females (p=0.004). In addition, a significant
      increase (p<0.001) in cells having multiple signals beyond those expected from a
      single cellular error was observed in the older compared to younger study
      participants, with these imbalances resulting from cells having either a single
      micronucleus with multiple signals, or cells having multiple MN. Collectively,
      these findings suggest that age-related increases in MN frequencies reflect both
      gains in the occurrence of similar cellular errors, as well as changes in the
      types of chromosomal findings that occur. Importantly, these results also
      illustrate that while MN frequencies reflect acquired abnormalities, they may
      also reflect cellular responses to "correct" an error, particularly when
      evaluated in young individuals. Therefore, when analyzing MN frequencies, one may
      also wish to evaluate the imbalances present in both the binucleates and MN to
      facilitate the recognition of varying cellular responses to environmental or
      genotoxic exposures.

PMID- 22613871
TI  - Neural correlates of establishing, maintaining, and switching brain states.
AB  - Although the study of brain states is an old one in neuroscience, there has been
      growing interest in brain state specification owing to MRI studies tracing brain
      connectivity at rest. In this review, we summarize recent research on three
      relatively well-described brain states: the resting, alert, and meditation
      states. We explore the neural correlates of maintaining a state or switching
      between states, and argue that the anterior cingulate cortex and striatum play a
      critical role in state maintenance, whereas the insula has a major role in
      switching between states. Brain state may serve as a predictor of performance in
      a variety of perceptual, memory, and problem solving tasks. Thus, understanding
      brain states is critical for understanding human performance.

PMID- 22613873
TI  - Why the exclusion of older people from clinical research must stop.

PMID- 22613874
TI  - Fashion fads in global health.

PMID- 22613872
TI  - Arrested development? Reconsidering dual-systems models of brain function in
      adolescence and disorders.
AB  - The dual-systems model of a ventral affective system, whose reactivity confers
      risks and liabilities, and a prefrontal control system, whose regulatory
      capacities buffer against these vulnerabilities, is an intuitive account that
      pervades many fields in the cognitive neurosciences--especially in the study of
      populations that differ from neurotypical adults, such as adolescents or
      individuals with affective or impulse regulation disorders. However, recent
      evidence that is inconsistent with dual-systems models illustrates the complexity
      of developmental and clinical variations in brain function. Building new models
      to account for this complexity is critical to progress in these fields, and will
      be facilitated by research that emphasizes network-based approaches and maps
      relationships between structure and function, as well as brain and behavior, over
      time.

PMID- 22613875
TI  - The rise of the pop psychologists.

PMID- 22613876
TI  - Effect of continuous cerebrospinal fluid drainage on therapeutic intensity in
      severe traumatic brain injury.
AB  - BACKGROUND: The aim of this study in patients with traumatic brain injury (TBI)
      was to assess the effectiveness of continuous cerebrospinal fluid (CSF) drainage
      in controlling intracranial pressure (ICP) and minimizing the use of other ICP
      lowering interventions potentially associated with serious adverse events.
      METHODS: We studied 20 TBI patients. In each patient, we compared four
      consecutive 12-hour periods covering the 24 hours before CSF drainage (NoDr1 and
      NoDr2) and the 24 first hours of drainage (Dr1 and Dr2). During each period, we
      recorded ICP, cerebral perfusion pressure (CPP), sedation, propofol infusion
      rate, and number of hypertonic saline boluses. RESULTS: With continuous CSF
      drainage, ICP decreased significantly from 18 +/- 6 mmHg (NoDr1) and 19 +/- 7
      mmHg (NoDr2) to 11 +/- 5 mmHg (Dr1) and 12 +/- 7 mmHg (Dr2). CPP increased
      significantly with drainage. Drainage led to a significant decrease in the number
      of hypertonic saline boluses required for ICP elevation, from 35 in 16 patients
      (80%) (NoDr1/2) to eight in five patients (25%) (Dr3/4). Drainage was not
      associated with changes in the midazolam or sufentanil infusion rates. The
      propofol infusion rate was non-significantly lower with drainage. No significant
      differences in serum sodium, body temperature, or PaCO(2) occurred across the
      four 12-hour periods. CONCLUSION: CSF drainage may not only lower ICP levels, but
      also decreases treatment intensity during the 24 hours following EVD placement in
      TBI patients. Because EVD placement may be associated with adverse event, the
      exact role for each of the available ICP-lowering interventions remains open to
      discussion.

PMID- 22613877
TI  - Clinicopathological features of centronuclear myopathy in Japanese populations
      harboring mutations in dynamin 2.
AB  - BACKGROUND: Missense mutations in dynamin 2 gene (DNM2) are associated with
      autosomal dominant centronuclear myopathy (CNM) with characteristic
      histopathological findings of centrally located myonuclei in a large number of
      muscle fibers. METHODS: To identify Japanese CNM caused by DNM2 mutations (DNM2
      CNM), we sequenced DNM2 in 22 unrelated Japanese patients who were pathologically
      diagnosed with CNM. The clinical and pathological findings of DNM2-CNM in
      patients were reviewed. RESULTS: We identified 3 different heterozygous missense
      mutations (p.E368K, p.R369W, and p.R465W) in 4 probands from 4 families.
      Clinically, calf muscle atrophy and pes cavus are features that are highly
      suggestive of DNM2-CNM among all CNMs. Pathologically, all 4 DNM2-CNM patients
      showed a radial distribution of myofibrils in scattered fibers, type 1 fiber
      atrophy, type 1 fiber predominance, and type 2C fibers. None of the non-DNM2-CNM
      patients exhibited all the 4 abovementioned pathological features, although some
      patients showed radial distribution without type 1 fiber atrophy and/or type 2C
      fibers. DISCUSSION: These results indicate that the clinicopathological features
      of DNM2-CNM are rather homogeneous and can be distinguished from the features of
      non-DNM2-CNM.

PMID- 22613878
TI  - A new evaluation method for the intracranial volume changes and subdural effusion
      of patients following endoscopic third ventriculostomy.
AB  - OBJECTIVE: Endoscopic third ventriculostomy (ETV) is a procedure commonly applied
      in the treatment of non-communicating (obstructive) hydrocephalus. One of the
      rare complications that can occur following ETV is a subdural effusion, even
      though this procedure is considered to be a more controlled and natural method of
      cerebrospinal fluid drainage compared to external drainage. In this study, we
      evaluated the intracranial volume changes and subdural effusion of patients
      following ETV using Cavalieri method. METHOD: Volumes analysis of the cranial
      cavity, brain, ventricles and subdural effusions of two patients after ETV were
      performed on computed tomography images using the Cavalieri principle, one of the
      stereological methods. RESULTS: The preoperative total intracranial volumes and
      the preoperative brain volumes decreased for both patients during the
      postoperative 3rd, 10th and 30th days. Following ETV, the volumes of the lateral
      ventricles of both patients initially decreased during the postoperative 3rd and
      10th days, however, the volumes returned almost to their preoperative size by the
      end of the 30th day. The effusions were seen on the postoperative 3rd and 10th
      days resolved by the end of the 30th day. CONCLUSION: Our results show that the
      Cavalieri method can be used to unbiased prediction of intracranial volume
      changes and to follow the subdural effusion after the ETV surgery.

PMID- 22613879
TI  - On the cellular processing of non-viral nanomedicines for nucleic acid delivery:
      mechanisms and methods.
AB  - In the field of nanomedicine, ample attention has been paid to the development of
      nanocarriers for the intracellular delivery of therapeutic cargo, such as nucleic
      acids for gene therapy. The efficiency with which these non-viral carriers
      deliver their payload at the required intracellular site of action remains low.
      Despite extensive research on cellular attachment, endocytosis and intracellular
      trafficking of nanocarriers, clear-cut rules for the design of effective
      nanocarriers to improve nucleic acid transfer are still lacking. This is mainly
      caused by the cell type-dependence of this highly dynamic cellular processing,
      and to the lack of reliable methods to study these events. For these reasons
      there is a strong demand for the development and standardization of such methods
      in order to better understand the intracellular dynamics of nanomedicine
      processing and validate cellular and intracellular targeting strategies. This
      review aims at providing an overview of the different processes that are
      currently known to be involved in the cellular processing of nanomedicines, with
      a focus on cellular internalization mechanisms, as this has received a great deal
      of attention in the last couple of years. Furthermore, the intracellular hurdles
      that need to be overcome to allow efficient NA transfer will be critically
      discussed. In addition, an overview will be given of various methodologies that
      have been applied to unravel these cellular processing mechanisms, with a
      discussion on their strengths and weaknesses.

PMID- 22613882
TI  - Amphiphilic poly(L-amino acids) - new materials for drug delivery.
AB  - The formulation of drug compounds into medicines will increasingly rely on the
      use of specially tailored molecules, which fundamentally alter the drug's
      pharmacokinetics to enable its therapeutic activity. This is particularly true of
      the more challenging hydrophobic drugs or therapeutic biological molecules. The
      demand for such enabled medicines will translate into a demand for advanced
      highly functionalised drug delivery materials. Polymers have been used to
      formulate medicines for many decades and this is unlikely to change soon.
      Amphiphilic polymers based on amino acids are the subject of this review. These
      molecules, which present as either poly(L-amino acid) block copolymers or poly(L
      amino acid) backbones with hydrophobic substituents, self assemble into micelles,
      vesicles, nanofibres and solid nanoparticles and such self assemblies, have drug
      delivery capabilities. The nature of the self-assembly depends on the chemistry
      of the constituent molecules, with the more hydrophilic molecules forming
      nanosized micellar aggregates including peptide nanofibres, molecules of
      intermediate hydrophobicity forming polymeric vesicles and the more hydrophobic
      variants forming amorphous polymeric nanoparticles of 100-1000 nm in diameter.
      The self-assemblies may be loaded with drugs or may present as micelle forming
      polymer-drug conjugates and the supramolecular aggregates have been employed as
      drug solubilisers, tumour targeting agents, gene delivery vectors and
      facilitators of intracellular drug uptake, with a more promising polymer-drug
      conjugate progressing to clinical testing.

PMID- 22613881
TI  - P(HPMA)-block-P(LA) copolymers in paclitaxel formulations: polylactide
      stereochemistry controls micellization, cellular uptake kinetics, intracellular
      localization and drug efficiency.
AB  - In order to explore the influence of polymer microstructure and stereochemistry
      in biological settings, the synthesis, micellization, cellular fate and the use
      in paclitaxel formulations of poly(N-(2-hydroxypropyl)-methacrylamide)-block
      poly(L-lactide) (P(HPMA)-block-P(LLA)) and poly(N-(2-hydroxypropyl)
      methacrylamide)-block-poly(DL-lactide) block copolymers (P(HPMA)-block-P(DLLA))
      were studied. To this end, P(HPMA)-block-P(lactide) block copolymers and their
      fluorescently labeled analogues were synthesized. The polymers exhibited
      molecular weights M(n) around 20,000 g/mol with dispersities (D=M(w)/M(n)) below
      1.3. In addition, the solution conformation of this new type of partially
      degradable amphiphilic block copolymers was studied with and without paclitaxel
      loading in PBS buffer (pH 7.2), employing fluorescence correlation spectroscopy
      (FCS). We observed polymeric micelles with a hydrodynamic diameter of 17.0 nm for
      a fluorescently labeled P(HPMA)-block-P(LLA) block copolymer (P2*) and 20.4 nm
      for a P(HPMA)-block-P(DLLA) block copolymer (P3*). For the corresponding loaded
      block copolymers aggregates with a diameter of 40.0 nm (P2*) and 41.4 nm (P3*) in
      formulations containing 17 wt.% paclitaxel were observed, respectively. While the
      block copolymer itself showed non-toxic behavior up to a concentration of 3 mg/mL
      in HeLa (human cervix adenocarcinoma) cells, the paclitaxel containing
      formulations showed IC 50 values in the range of 10-100 nM. The P(HPMA)-block
      P(DLLA) polymer (P3*) enters the cells more efficiently than stereo regular
      polymer (P2*) via an energy-dependent uptake mechanism. Thus, differences in the
      IC(50) value are--most likely--attributed to significant changes in cellular
      uptake. Polymer tacticity and stereoregularity appear to represent a key feature
      determining cellular uptake and efficiency for the PLA block copolymer drug
      formulations. This work demonstrates the importance of the microstructure of
      polymers used in drug delivery systems (DDS).

PMID- 22613883
TI  - Interventional Management of Stroke III trial: establishing the foundation.

PMID- 22613880
TI  - Opportunities and challenges for use of tumor spheroids as models to test drug
      delivery and efficacy.
AB  - Multicellular spheroids are three dimensional in vitro microscale tissue analogs.
      The current article examines the suitability of spheroids as an in vitro platform
      for testing drug delivery systems. Spheroids model critical physiologic
      parameters present in vivo, including complex multicellular architecture,
      barriers to mass transport, and extracellular matrix deposition. Relative to two
      dimensional cultures, spheroids also provide better target cells for drug testing
      and are appropriate in vitro models for studies of drug penetration. Key
      challenges associated with creation of uniformly sized spheroids, spheroids with
      small number of cells and co-culture spheroids are emphasized in the article.
      Moreover, the assay techniques required for the characterization of drug delivery
      and efficacy in spheroids and the challenges associated with such studies are
      discussed. Examples for the use of spheroids in drug delivery and testing are
      also emphasized. By addressing these challenges with possible solutions,
      multicellular spheroids are becoming an increasingly useful in vitro tool for
      drug screening and delivery to pathological tissues and organs.

PMID- 22613885
TI  - The structure of common and uncommon mental disorders.
AB  - BACKGROUND: Co-morbidity patterns in epidemiological studies of mental illness
      consistently demonstrate that a latent internalizing factor accounts for co
      morbidity patterns among unipolar mood and anxiety disorders, whereas a latent
      externalizing factor underlies the covariation of substance-use disorders and
      antisocial behaviors. However, this structure needs to be extended to include a
      broader range of disorders. METHOD: Exploratory and confirmatory factor analyses
      were used to examine the structure of co-morbidity using data from the
      Collaborative Psychiatric Epidemiological Surveys (n = 16 233). RESULTS: In the
      best-fitting model, eating and bipolar disorders formed subfactors within
      internalizing, impulse control disorders were indicators of externalizing, and
      factor-analytically derived personality disorder scales split between
      internalizing and externalizing. CONCLUSIONS: This was the first large-scale
      nationally representative study that has included uncommon mental disorders with
      sufficient power to examine their fit within a structural model of
      psychopathology. The results of this study have important implications for
      conceptualizing myriad mental disorders.

PMID- 22613884
TI  - Speckle tracking-derived myocardial tissue deformation imaging in twin-twin
      transfusion syndrome: differences in strain and strain rate between donor and
      recipient twins.
AB  - OBJECTIVES: Twin-twin transfusion syndrome (TTTS) is a complex disorder with
      altered cardiovascular loading conditions that affects both donors and
      recipients. Myocardial tissue deformation analysis using vector velocity imaging
      is an angle-independent, speckle-tracking technique which can assess myocardial
      mechanics and may provide insight into cardiac dysfunction in TTTS. METHODS:
      Digital dynamic two-dimensional four-chamber views were interrogated offline.
      Images were acquired utilizing standard video frame rates (30 frames/s). The
      global longitudinal strain, systolic strain rate, and diastolic strain rate were
      measured in the left (LV) and right ventricles (RV) of 25 fetal pairs with TTTS
      and compared to 25 gestational age-matched normal controls. Pulsatility indices
      for the umbilical artery and middle cerebral artery were measured. RESULTS: The
      gestational age at evaluation was 20.5 +/- 1.3 weeks. The donor LV systolic
      strain rate was higher, while the donor RV diastolic strain rate was
      significantly lower, than control values. The recipient longitudinal strain,
      systolic strain rate, and diastolic strain rate were significantly lower for both
      LV and RV in comparison to controls. The donor umbilical artery pulsatility index
      was higher than control values (1.92 +/- 0.45 vs. 1.41 +/- 0.25, p < 0.001),
      while the donor middle cerebral artery pulsatility index was lower (1.46 +/- 0.28
      vs. 1.87 +/- 0.21). Recipient umbilical artery and middle cerebral artery
      pulsatility indices were no different than control values. CONCLUSIONS: In TTTS,
      both the donor and the recipient exhibit abnormalities of myocardial tissue
      deformation with ventricle-specific changes evident based on loading conditions.
      Donor LV systolic function is hyperdynamic due to hypovolemia and selective
      ejection into a low-resistance cerebrovascular circuit while the donor RV
      selectively ejects into a high-resistance placental circuit. Recipient RV and LV
      are both globally depressed with systolic and diastolic dysfunction. Further
      prospective validation of our findings using high frame rate analysis is
      indicated.

PMID- 22613886
TI  - Experimental investigation on an entrained flow type biomass gasification system
      using coconut coir dust as powdery biomass feedstock.
AB  - Based on an entrained flow concept, a prototype atmospheric gasification system
      has been designed and developed in the laboratory for gasification of powdery
      biomass feedstock such as rice husks, coconut coir dust, saw dust etc. The
      reactor was developed by adopting L/D (height to diameter) ratio of 10, residence
      time of about 2s and a turn down ratio (TDR) of 1.5. The experimental
      investigation was carried out using coconut coir dust as biomass feedstock with a
      mean operating feed rate of 40 kg/h The effects of equivalence ratio in the range
      of 0.21-0.3, steam feed at a fixed flow rate of 12 kg/h, preheat on reactor
      temperature, product gas yield and tar content were investigated. The gasifier
      could able to attain high temperatures in the range of 976-1100  degrees C with
      gas lower heating value (LHV) and peak cold gas efficiency (CGE) of 7.86 MJ/Nm3
      and 87.6% respectively.

PMID- 22613887
TI  - Distribution of methanogenic potential in fractions of turf grass used as
      inoculum for the start-up of thermophilic anaerobic digestion.
AB  - This study aims to investigate thermophilic methanogens in turf used as an
      inoculum. Results showed that Methanoculleus sp. regarded as hydrogenotrophic and
      Methanosarcina sp. regarded as acetoclastic methanogens were present in turf
      tested. However, active acetoclastic methanogens were present in turf soil only.
      The current study showed that thermophilic methanogens were present in various
      turf grass species: Stenotaphrum secundatum, Cynodon dactylon, and Zoysia
      japonica. Severe treatments of grass leaves under oxic conditions, including
      blending, drying and pulverizing did not affect the thermophilic hydrogenotrophic
      methanogenic activity of the grass. A dried and pulverized grass extract could be
      generated that can serve as a readily storable methanogenic inoculum for
      thermophilic anaerobic digestion. The methanogens could also be physically
      extracted into an aqueous suspension, suitable as an inoculum. The possible
      contribution of the presence of methanogens on grass plants to global greenhouse
      emissions is briefly discussed.

PMID- 22613888
TI  - Hot water extraction and steam explosion as pretreatments for ethanol production
      from spruce bark.
AB  - Spruce bark is a source of interesting polyphenolic compounds and also a
      potential but little studied feedstock for sugar route biorefinery processes.
      Enzymatic hydrolysis and fermentation of spruce bark sugars to ethanol were
      studied after three different pretreatments: steam explosion (SE), hot water
      extraction (HWE) at 80  degrees C, and sequential hot water extraction and steam
      explosion (HWE+SE), and the recovery of different components was determined
      during the pretreatments. The best steam explosion conditions were 5 min at 190 
      degrees C without acid catalyst based on the efficiency of enzymatic hydrolysis
      of the material. However, when pectinase was included in the enzyme mixture, the
      hydrolysis rate and yield of HWE bark was as good as that of SE and HWE+SE barks.
      Ethanol was produced efficiently with the yeast Saccharomyces cerevisiae from the
      pretreated and hydrolysed materials suggesting the suitability of spruce bark to
      various lignocellulosic ethanol process concepts.

PMID- 22613889
TI  - Multiple amino acid substitutions significantly improve the thermostability of
      feruloyl esterase A from Aspergillus niger.
AB  - Feruloyl esterase A from Aspergillus niger (AnFaeA) is one of the most important
      feruloyl esterases of industrial relevance. Previous work aided by the PoPMuSiC
      algorithm has identified two beneficial mutants (D93G and S187F) with
      thermostabilization effect. In this work, twelve additional amino acid
      substitutions were identified to be beneficial to the thermostability of AnFaeA
      after screening a random mutagenesis library constructed in Pichia pastoris.
      Combination of these mutations resulted in a mutant with 80% residual activity
      after heat treatment at 90  degrees C for 15 min and a half-life increasing from
      15 min to >4000 min at 55  degrees C. The thermostabilized mutant displayed
      significantly enhanced performance compared to the parental AnFaeA when applied
      to the treatment of steam-exploded corn stalk at 60  degrees C together with an
      xylanase, demonstrating its great potential for industrial application.

PMID- 22613890
TI  - Biodegradation of aniline in an alkaline environment by a novel strain of the
      halophilic bacterium, Dietzia natronolimnaea JQ-AN.
AB  - Dietzia natronolimnaea JQ-AN was isolated from industrial wastewater containing
      aniline. Under aerobic conditions, the JQ-AN strain degraded 87% of the aniline
      in a 300 mg L(-1) aniline solution after 120 h of shake flask incubation in a
      medium containing sodium acetate. This strain had an unusually high salinity
      tolerance in minimal medium (0-6% NaCl, w/v). The optimal pH for microbial growth
      and aniline biodegradation was pH 8.0. Two liters of simulated aniline wastewater
      was created in a reactor at pH 8.0 and 3% NaCl (w/v), and biodegradation of
      aniline was tested over 7 days at 30  degrees C. For the initial concentrations
      of 100, 300, and 500 mg L(-1), 100%, 80.5% and 72% of the aniline was degraded,
      respectively. Strain JQ-AN may use an ortho-cleavage pathway for dissimilation of
      the catechol intermediate.

PMID- 22613891
TI  - Evolution of the microbial community in a full-scale printing and dyeing
      wastewater treatment system.
AB  - In this study, the dynamics of bacterial, fungal and archaeal populations in two
      stage biological processes of a full-scale printing and dyeing wastewater
      treatment system were traced using cultivation and molecular biological
      techniques. The enumeration results indicated that bacteria were the dominant
      population in the system, in which the ratio of fungi to bacteria decreased in
      all the treatment units, while the ratio of archaea to bacteria increased
      significantly, especially in samples from the second-stage biological treatment
      process. PCR-denaturing gradient gel electrophoresis (DGGE) analysis showed that
      the microbial diversity increased with system running and 64.6% of bacterial,
      57.6% of fungal and 38.2% of archaeal populations remained in the system from the
      seed sludge during system start-up. In spite of variation in the microbial
      community and composition of the influents, some bacterial species such as
      Thauera sp. and Xanthomonadaceae were present simultaneously in all the collected
      samples.

PMID- 22613892
TI  - Nannochloropsis production metrics in a scalable outdoor photobioreactor for
      commercial applications.
AB  - Commercial production of renewable energy feedstocks from microalgae will require
      reliable and scalable growth systems. Two and one half years of biomass and lipid
      productivity data were obtained with an industrial-scale outdoor photobioreactor
      operated in Fort Collins, Colorado (USA). The annualized volumetric growth rates
      for Nannochloropsis oculata (CCMP 525) and Nannochloropsis salina (CCMP 1776)
      were 0.16 g L(-1) d(-1) (peak=0.37 g L(-1) d(-1)) and 0.15 g L(-1) d(-1)
      (peak=0.37 g L(-1) d(-1)) respectively. The collective average lipid production
      was 10.7 m3 ha(-1) yr(-1) with a peak value of 36.3 m3 ha(-1) yr(-1). Results
      from this study are unique based on publication of biomass and corresponding
      lipid content combined with demonstration of energy savings realized through
      analysis of gas delivery requirements, water recycling from successive harvests
      with no effect on productivity, and culture stability through serial batch
      lineage data and chemotaxonomic analysis of fatty acid contents.

PMID- 22613893
TI  - Electricity generation and microbial community in a submerged-exchangeable
      microbial fuel cell system for low-strength domestic wastewater treatment.
AB  - A submerged type microbial fuel cell (MFC) system, which consisted of six readily
      exchangeable air-cathode MFCs, was evaluated for continuous treatment of low
      strength domestic wastewater. When supplied with synthetic wastewater (COD 100
      mg/L), the system showed increasing maximum power densities from 191 to 754 mW/m2
      as COD loading rates increased (0.20-0.40 kg/m3/day). COD removal efficiencies
      decreased with increased COD loading rates but the effluent COD concentrations
      met the relevant effluent quality standard (CODMn 20 mg/L) at all conditions. The
      system was then operated with domestic wastewater (c.a. 100 mg COD/L) at 0.32 and
      0.43 kg/m3/day. The system showed much lower power densities (116-149 mW/m2) at
      both loading rates, compared to synthetic wastewater. Anodic microbial
      communities were completely different when the wastewater type was changed. These
      results suggest that the newly developed MFC system could be applied to treat low
      strength domestic wastewater without requiring any additional organic removal
      stage.

PMID- 22613894
TI  - Decolourisation of textile wastewater in a submerged anaerobic membrane
      bioreactor.
AB  - Azo dye decolourisation can be easily achieved by biological reduction under
      anaerobic conditions. The aim of this study was to evaluate the applicability of
      submerged anaerobic membrane bioreactors (SAMBRs) for the decolourisation of
      dyeing wastewater containing azo dyes. The reactive orange 16 was used as model
      of an azo dye. The results demonstrated that very high decolourisation (higher
      than 99%) can be achieved by SAMBRs. Although decolourisation was not
      significantly influenced by the azo dye concentrations up to 3.2 g L(-1), methane
      production was greatly inhibited (up to 80-85%). Since volatile fatty acids
      accumulated in the treatment system with the azo dye concentration increase,
      methanogenes seem to be the most sensitive microbial populations of the anaerobic
      ecological community. The results demonstrated that anaerobic process combined
      with membrane filtration can deal with highly concentrated wastewaters that
      result from stream separation of industrial discharges.

PMID- 22613895
TI  - Effects of laccase on lignin depolymerization and enzymatic hydrolysis of ensiled
      corn stover.
AB  - The aim of this study was to explore the synergies of laccase, a ligninolytic
      enzyme, with cellulose and hemicellulase amendments on ensiled corn stover.
      Molecular signals of lignin decomposition were observed by tetramethylammonium
      hydroxide thermochemolysis and gas chromatography-mass spectroscopy (TMAH-GC-MS)
      analysis. The significant findings suggest that ensilage might provide a platform
      for biological pretreatment. By partially hydrolyzing cellulose and hemicellulose
      into soluble sugars, ensilage facilitates laccase penetration into the
      lignocellulose complex to enhance lignin degradation. Downstream cellulose
      hydrolysis was improved 7% with increasing laccase loading rate. These results
      demonstrate the potential of enzymes, either directly amended or expressed by
      microbes during ensilage, to maximize utilization of corn stover for cellulosic
      biofuels and other downstream fermentations.

PMID- 22613896
TI  - Impact of hardwood species on production cost of second generation ethanol.
AB  - The present work targeted the understanding of the influence of nine different
      hardwood species as feedstock on ethanol production yield and costs. It was found
      that the minimum ethanol revenue (MER) ($ per gallon to the producer) to achieve
      a 12% internal rate of return (IRR) on invested capital was smaller for low
      lignin content samples and the influence of species characteristics remained
      restricted to high residual lignin content. We show that if the pretreatment
      being applied to the feedstock targets or is limited to low lignin removal, one
      can expect the species to have a significant impact on overall economics, playing
      important role to project success. This study also showed a variation of up to
      40% in relative MER among hardwood species, where maple, globulus and sweet gum
      varied the least. Sensitivity analysis showed ethanol yield per ton of feedstock
      had the largest influence in MER, followed by CAPEX.

PMID- 22613897
TI  - Enhanced rhamnolipids production by Pseudomonas aeruginosa based on a pH stage
      controlled fed-batch fermentation process.
AB  - Rhamnolipids find broad applications as natural surfactants, emulsifiers, and
      antibiotics because of their low toxicity, high biodegradability and
      environmental soundness. In this study, a pH stage-controlled process of
      fermentation of rhamnolipids by Pseudomonas aeruginosa O-2-2 was established. A
      yield of 24.06 g/L in batch fermentation was achieved in a 5-L fermentor via the
      optimization of stirring speed. By controlling pH, rhamnolipid production was
      increased to 28.8 g/L, an improvement of 19.7%, and more substrate was converted
      to rhamnolipids rather than to biomass. Fermentation kinetics models for cell
      growth, product synthesis and substrate consumption based on the pH stage
      controlled fermentation indicated that rhamnolipid production could be further
      improved by fed-batch fermentation. Rhamnolipid production reached 70.56 g/L, an
      improvement of 193%, in the pH stage-controlled fed-batch fermentation when the
      stirring speeds was controlled at 500 rpm and the fermentation temperature was
      maintained at 30  degrees C.

PMID- 22613898
TI  - Effect of earthworms on the performance and microbial communities of excess
      sludge treatment process in vermifilter.
AB  - Previous studies have shown that the stabilization of excess sludge by
      vermifiltration can be improved significantly through the use of earthworms. To
      investigate the effect of earthworms on enhancing sludge stabilization during the
      vermifiltration process, a vermifilter (VF) with earthworms and a conventional
      biofilter (BF) without earthworms were compared. The sludge reduction capability
      of the VF was ~85% higher than that of the BF. Specifically, elemental analysis
      indicated that earthworms enhanced the stabilization of organic matter.
      Furthermore, earthworm predation strongly regulated microbial biomass while
      improving microbial activity. Denaturing gradient gel electrophoresis (DGGE)
      analysis showed that the most abundant microbes in the VF biofilms and earthworm
      casts were Flavobacterium, Myroides, Sphingobacterium, and Myxococcales, all of
      which are known to be highly effective at degrading organic matter. These results
      indicate that earthworms can improve the stabilization of excess sludge during
      vermifiltration, and reveal the processes by which this is achieved.

PMID- 22613899
TI  - Cellulose solvent- and organic solvent-based lignocellulose fractionation enabled
      efficient sugar release from a variety of lignocellulosic feedstocks.
AB  - Developing feedstock-independent biomass pretreatment would be vital to second
      generation biorefineries that would fully utilize diverse non-food
      lignocellulosic biomass resources, decrease transportation costs of low energy
      density feedstock, and conserve natural biodiversity. Cellulose solvent- and
      organic solvent-based lignocellulose fractionation (COSLIF) was applied to a
      variety of feedstocks, including Miscanthus, poplar, their mixture, bagasse,
      wheat straw, and rice straw. Although non-pretreated biomass samples exhibited a
      large variation in enzymatic digestibility, the COSLIF-pretreated biomass samples
      exhibited similar high enzymatic glucan digestibilities and fast hydrolysis
      rates. Glucan digestibilities of most pretreated feedstocks were ~93% at five
      filter paper units per gram of glucan. The overall glucose and xylose yields for
      the Miscanthus:poplar mixture at a weight ratio of 1:2 were 93% and 85%,
      respectively. These results suggested that COSLIF could be regarded as a
      feedstock-independent pretreatment suitable for processing diverse feedstocks by
      adjusting pretreatment residence time only.

PMID- 22613900
TI  - Xylo-oligosaccharides are competitive inhibitors of cellobiohydrolase I from
      Thermoascus aurantiacus.
AB  - The effects of xylo-oligosaccharides (XOS) and xylose on the hydrolytic
      activities of cellulases, endoglucanase II (EGII, originating from Thermoascus
      aurantiacus), cellobiohydrolase I (CBHI, from T. aurantiacus), and
      cellobiohydrolase II (CBHII, from Trichoderma reesei) on Avicel and nanocellulose
      were investigated. After the addition of XOS, the amounts of cellobiose, the main
      product released from Avicel and nanocellulose by CBHI, decreased from 0.78 and
      1.37 mg/ml to 0.59 and 1.23 mg/ml, respectively. During hydrolysis by CBHII, the
      amounts of cellobiose released from the substrates were almost cut in half after
      the addition of XOS. Kinetic experiments showed that xylobiose and xylotriose
      were competitive inhibitors of CBHI. The results revealed that the strong
      inhibition of cellulase by XOS can be attributed to the inhibitory effect of XOS
      especially on cellobiohydrolase I. The results indicate the necessity to totally
      hydrolyze xylo-oligosaccharides into the less inhibitory product, xylose, to
      increasing hydrolytic efficiency.

PMID- 22613901
TI  - A pooled analysis of infections, malignancy, and mortality in infliximab- and
      immunomodulator-treated adult patients with inflammatory bowel disease.
AB  - OBJECTIVES: The objective of this study was to analyze the safety of long-term
      infliximab treatment, with/without concomitant immunomodulators, across Crohn's
      disease (CD) and ulcerative colitis (UC) clinical trials. METHODS: To maximize
      sample size, we pooled primary safety data across 10 CD or UC trials, including
      five randomized, controlled trials contributing data from patients who received
      intravenous infliximab 5 or 10 mg/kg (n=1,713; +/-azathioprine) or placebo
      (n=406; +/-azathioprine). Pooled incidences and 95% confidence intervals (CIs)
      were determined for mortality, infection, and malignancy. Standardized incidence
      ratios and 95% CIs were also determined for malignancies using the Surveillance,
      Epidemiology, and End Results database. RESULTS: We observed no increase in
      infections, serious infections, or malignancy with infliximab vs. placebo in
      these patients with inflammatory bowel disease (IBD). In patients with UC, but
      not CD, immunomodulator treatment (vs. treatment without immunomodulator) yielded
      a higher incidence (95% CI) of infections (120.07 (110.66, 130.08)/100 patient
      years (pt-yrs) vs. 92.47 (84.54, 100.94)/100 pt-yrs). Among placebo-treated
      patients with CD, but not UC, those with immunomodulator use demonstrated a
      higher incidence (95% CI) of malignancy vs. no immunomodulator treatment (1.84
      (0.22, 6.66)/100 pt-yrs vs. 0.00 (0.00, 0.00)/100 pt-yrs). Mortality and
      infection-related mortality appeared unaffected by infliximab or immunomodulator
      treatment. CONCLUSIONS: Infliximab treatment of IBD did not appear to affect
      incidences of infection, mortality, or malignancy. Relative to patients with no
      immunomodulator use, immunomodulator-treated UC patients demonstrated a higher
      incidence of infection and immunomodulator-plus-placebo-treated CD patients
      demonstrated a higher incidence of malignancy.

PMID- 22613902
TI  - The epidemiology of colectomy in ulcerative colitis: results from a population
      based cohort.
AB  - OBJECTIVES: Previous studies have reported colectomy rates of over 50% in
      ulcerative colitis (UC), although changes in management may have influenced the
      rates of colectomy in the modern era. We sought to determine the incidence of
      colectomy in UC and identify risk factors associated with early colectomy (EC)
      and late colectomy (LC). METHODS: We used the University of Manitoba Inflammatory
      Bowel Disease Epidemiology Database, a population-based data set including UC
      patients with up to 25 years of post diagnosis follow-up. We tracked the
      occurrence of total colectomy in all patients with known UC, subdivided into EC
      (<=90 days from diagnosis date) and LC (>90 days from diagnosis). Survival curves
      were created and stratified by age, sex, era of diagnosis, and inpatient/hospital
      diagnosis. Cox proportional hazards modeling was used to determine which risk
      factors were predictive of either EC or LC. RESULTS: Among 3,752 patients with
      UC, 367 underwent colectomy. The 5-, 10- and 20-year actuarial risk of requiring
      colectomy was 7.5%, 10.4%, and 14.8%, respectively. Male sex (hazard ratio (HR):
      2.63, [corrected] 95% confidence interval (CI): 1.58-4.36) and being initially
      diagnosed during a hospitalization (HR: 12.46, 95% CI: 7.40-21.0) were predictive
      of EC after adjustment for confounders. In-hospital diagnosis was predictive of
      LC, whereas being diagnosed more recently was protective against LC (HR: 0.96,
      95% CI: 0.93-0.98). CONCLUSIONS: The cumulative incidence of colectomy in UC is
      lower than previously reported, and appears to be decreasing further among more
      recently diagnosed cohorts of patients. Male sex and hospitalization at the time
      of diagnosis are major risk factors for EC and LC.

PMID- 22613903
TI  - Narrow band imaging for detection of dysplasia in colitis: a randomized
      controlled trial.
AB  - OBJECTIVES: In ulcerative colitis surveillance, chromoendoscopy improves
      dysplasia detection 3 - 5-fold compared with white light endoscopy (WLE). The aim
      of this study was to investigate whether narrow band imaging (NBI) can improve
      dysplasia detection compared with WLE. METHODS: This was a randomized, parallel
      group trial. A total of 220 patients were needed to be recruited to detect a
      threefold increase in dysplasia detection. In all, 112 patients with long
      standing ulcerative colitis were randomized to colonoscopic extubation with NBI
      (56) or WLE (56) (1:1 ratio) at two tertiary endoscopy units in the United
      Kingdom. Targeted biopsies of suspicious areas and quadrantic random biopsies
      every 10 cm were taken in both groups. The primary outcome measure was the
      proportion of patients with at least one area of dysplasia detected. In a
      prespecified mid-point analysis, the criteria for trial discontinuation were met
      and the trial was stopped and analyzed at this point. RESULTS: There was no
      difference in the primary outcome between the two groups, with 5 patients having
      at least one dysplastic lesion in each group (odds ratio (OR) 1.00, 95 %
      confidence interval (95 % CI) 0.27 - 3.67, P = 1.00). This remained unchanged
      when adjusted for other variables (OR 0.69, 95 % CI 0.16 - 2.96, P = 0.62).
      Overall, dysplasia detection was 9 % in each arm. Yield of dysplasia from random
      nontargeted biopsies was 1 / 2,707 (0.04 % ). CONCLUSIONS: Overall, in this
      multicenter parallel-group trial, there was no difference in dysplasia detection
      when using NBI compared with high-definition WLE colonoscopy. Random background
      biopsies were ineffective in detecting dysplasia.

PMID- 22613904
TI  - Long-term follow-up of 1,000 patients cured of Helicobacter pylori infection
      following an episode of peptic ulcer bleeding.
AB  - OBJECTIVES: To evaluate the effect of Helicobacter pylori (H. pylori) eradication
      on ulcer bleeding recurrence in a prospective, long-term study including 1,000
      patients. METHODS: Patients with peptic ulcer bleeding were prospectively
      included. Prior non-steroidal anti-inflammatory drug (NSAID) use was not
      considered exclusion criteria. H. pylori infection was confirmed by rapid urease
      test, histology, or (13)C-urea breath test. Several eradication therapies were
      used. Subsequently, ranitidine 150 mg o.d. was administered until eradication was
      confirmed by (13)C-urea breath test 8 weeks after completing therapy. Patients
      with therapy failure received a second, third, or fourth course of eradication
      therapy. Patients with eradication success did not receive maintenance anti-ulcer
      therapy and were controlled yearly with a repeat breath test. NSAID use was not
      permitted during follow-up. RESULTS: Thousand patients were followed up for at
      least 12 months, with a total of 3,253 patient-years of follow-up. Mean age 56
      years, 75% males, 41% previous NSAID users. In all, 69% had duodenal ulcer, 27%
      gastric ulcer, and 4% pyloric ulcer. Recurrence of bleeding was demonstrated in
      three patients at 1 year (which occurred after NSAID use in two cases, and after
      H. pylori reinfection in another one), and in two more patients at 2 years (one
      after NSAID use and another after H. pylori reinfection). The cumulative
      incidence of rebleeding was 0.5% (95% confidence interval, 0.16-1.16%), and the
      incidence rate of rebleeding was 0.15% (0.05-0.36%) per patient-year of follow
      up. CONCLUSION: Peptic ulcer rebleeding virtually does not occur in patients with
      complicated ulcers after H. pylori eradication. Maintenance anti-ulcer
      (antisecretory) therapy is not necessary if eradication is achieved. However,
      NSAID intake or H. pylori reinfection may exceptionally cause rebleeding in H.
      pylori-eradicated patients.

PMID- 22613905
TI  - Effect of gender on prevalence of irritable bowel syndrome in the community:
      systematic review and meta-analysis.
AB  - OBJECTIVES: Irritable bowel syndrome (IBS) is thought to be commoner in women.
      However, no systematic review has confirmed whether this is the case, or assessed
      whether any proposed female preponderance remains stable according to geography
      and criteria used to define IBS. Nor has effect of gender on subtype of IBS been
      examined systematically. METHODS: MEDLINE, EMBASE, and EMBASE Classic were
      searched (up to October 2011) to identify population-based studies reporting
      prevalence of IBS in adults (>=15 years) according to gender, and defined using
      symptom-based criteria, or questionnaire. The prevalence of IBS in women and men
      was extracted for all studies, and according to study location and diagnostic
      criteria used, and compared using odds ratios (ORs) with 95% confidence intervals
      (CIs). Prevalence of each subtype of IBS, according to predominant stool pattern,
      was compared in women and men with IBS. RESULTS: Of the 390 papers evaluated, 56
      studies containing 188,229 subjects were eligible. The OR for IBS in women,
      compared with men, in all studies was 1.67 (95% CI: 1.53-1.82). Prevalence of IBS
      was not significantly higher in women, compared with men, in South Asian, South
      American, or African studies. The OR was highest with the Rome I criteria (1.99;
      95% CI: 1.76-2.25), and lowest with the Rome II criteria (1.40; 95% CI: 1.24
      1.59). Women with IBS were more likely to exhibit the constipation-predominant
      subtype (OR: 2.38; 95% CI: 1.45-3.92), and less likely to meet criteria for the
      diarrhea-predominant subtype (OR: 0.45; 95% CI: 0.32-0.65) than men with IBS.
      CONCLUSIONS: Prevalence of IBS appeared modestly higher in women, and this
      remained relatively stable according to geography and criteria used to define its
      presence. However, among individuals with IBS, subtypes varied according to
      gender.

PMID- 22613906
TI  - Natural history following the first attack of acute pancreatitis.
AB  - OBJECTIVES: Data on natural history following a sentinel attack of acute
      pancreatitis (AP) are limited. The objective of this study was to determine the
      risk of recurrent AP (RAP) and subsequent chronic pancreatitis (CP) diagnosis
      after the first attack of AP. METHODS: Using the Pennsylvania Health Care Cost
      Containment Council (PHC4) data set, we identified all unique White and Black
      Allegheny County residents who received a first-time primary inpatient discharge
      diagnosis of AP from 1996 through 2005. AP etiology was determined using
      associated diagnoses codes. We also checked whether any of these patients were
      readmitted for AP and/or received inpatient CP diagnosis until third quarter of
      2007. RESULTS: In all, 7,456 unique residents (mean age 58+/-20 years, 45% male,
      80% White) with incident AP admission were identified. Common etiologies included
      biliary (28%), alcohol (19%), and idiopathic (36%). Compared with other causes,
      alcoholic AP patients were significantly younger and more likely to be male and
      Black. Among survivors (98.1%) and those without pancreatic cancer, follow-up
      (median 40 months, interquartile range 18, 69) was available for 84% of patients.
      Readmission for primary or any AP was recorded for 22 and 29%; subsequent primary
      or any CP diagnosis was assigned to 6 and 12.8%, respectively. Significant
      independent predictors for RAP were alcohol etiology and tobacco abuse and for CP
      were RAP and tobacco abuse. RAP risk in biliary AP increased with the duration
      between AP and cholecystectomy. CONCLUSIONS: Readmissions following a sentinel
      attack of AP are common. Progression to CP is infrequent and usually occurs in
      the setting of RAP, alcohol, and smoking. Cholectstectomy should be considered as
      soon as feasible after an attack of biliary AP. Natural history of CP may be
      altered through early behavioral intervention.

PMID- 22613907
TI  - Multisociety Sedation Curriculum for Gastrointestinal Endoscopy.

PMID- 22613908
TI  - Home dialysis in Japan. Introduction.

PMID- 22613909
TI  - A kinetic model for peritoneal dialysis and its application for complementary
      dialysis therapy.
AB  - Kinetic models have been used in both hemodialysis (HD) and peritoneal dialysis
      (PD) therapies. Since many different theoretical models are available, users
      should choose one of these models along with the purpose of their studies. In
      general, simple models are useful for clinical investigations as well as clinical
      research, while rigorous models may be useful for engineers and cannot be
      utilized without an aid of computers. Several pieces of commercial software that
      include rigorous models are available for evaluation of peritoneal permeabilities
      as well as for constructing prescriptions. One of these pieces was clinically
      evaluated and high correlations with correlation coefficients >0.98 were found
      between clinical and recalculated values of total Kt/V for urea, total creatinine
      clearances and the ultrafiltration volume. Although the overall mass transfer
      area coefficients (MTAC) of the peritoneal membrane is a diffusive parameter, it
      may become a useful tool for predicting peritoneal ultrafiltration by defining an
      index for peritoneal diffusive selectivity, the ratio of MTAC for urea to that
      for creatinine. It is recommended to use super high-flux dialyzers in PD+HD
      (complementary) combined therapy because it is the opportunity in a week to
      remove much middle and/or large molecules greater than beta(2)-microglobulin.
      Kinetic models are especially useful in treatments with relatively complex
      prescriptions such as PD+HD combined therapy, and may be a key to the further
      success of these modalities performed at home.

PMID- 22613910
TI  - How automated peritoneal dialysis is applied and maintained in Japan.
AB  - According to a nationwide statistical survey in Japan, only 9,858 patients (3.3%
      of dialysis patients) were on maintenance peritoneal dialysis (PD) at the end of
      2009. In this survey, 8,635 patients answered questions about the PD method,
      while 1,223 patients did not respond. In Japan, at the end of 2009, 5,143
      patients (59.6%) on PD were treated with CAPD and 3,492 patients (40.4%) on PD
      were treated with automated PD (APD). It is well known that around 20% of
      Japanese PD patients choose to apply and maintain PD + HD combination therapy.
      The number of PD + HD patients (1,569) accounted for 20.7% of the PD-treated
      patients (7,591). In Japan, patients with fluid overloading preferably select PD
      + HD combination therapy with or without icodextrin use. Young patients select
      APD while patients on PD suffered from fluid overloading with high transporter
      membrane. What then are the factors that effect APD selection in Japan? The use
      of various forms of APD has increased considerably in the past few years.
      Important factors that contribute to APD selection are better adjustment of APD
      to the patient's lifestyle and the flexibility that APD offers to patients. In
      addition, patients with APD will be able to have good quality of life (QOL).
      Young patients on PD select APD because of good QOL. It is well known that almost
      all of children younger than 19 years with end-stage renal disease (ESRD) are
      undergoing APD. APD has a pivotal role in the management of pediatric patients
      with ESRD. Children on APD had a lower incidence of peritonitis compared with
      those with CAPD. The switch from CAPD to APD resulted in better ultrafiltration,
      less edema, lower mean arterial blood pressure, lower peritonitis rate and fewer
      hospital admissions. As in young patients, APD is also good method to select in
      elderly patients on PD. The need for the exchange to be performed by another
      person is increased in elderly and handicapped ESRD patients, however APD therapy
      is a good selection for them because of the smaller number of manipulations,
      resulting in a substantial reduction of help required. In the future,
      telemedicine systems with APD may be play an important role for young and elderly
      patients on PD.

PMID- 22613911
TI  - Introduction and maintenance program for PD based on PD guidelines for Japan.
AB  - Peritoneal dialysis (PD) guidelines for Japan were first published by the
      Japanese Society for Dialysis Treatment in 2009. They presented a concrete frame
      of PD practiced in Japan and stressed the timing of PD introduction as well as
      the clinical point of transfer to other modalities. The outlines of the
      guidelines and the issues to be addressed in the future are reviewed.

PMID- 22613912
TI  - Appropriate drug dosing in patients receiving peritoneal dialysis.
AB  - The quantity of drugs removed during peritoneal dialysis is substantially lower
      than that during hemodialysis, and thus, the supplemental administration of
      drugs, even when they are efficiently removed during hemodialysis, is not
      necessary in patients receiving continuous ambulatory peritoneal dialysis (CAPD).
      However, because CAPD is a continuous hemocatharsis procedure, the cumulative
      removal of renally excretable drugs is higher in CAPD patients than in
      hemodialysis patients between sessions. Therefore, the weekly dosage of a drug
      can be approximately the same in CAPD patients and hemodialysis patients, and
      dosing design for patients with a pre-end-stage renal disease in the period prior
      to the initiation of dialysis can be applied to CAPD patients. Nevertheless, an
      appropriate dosage regimen, based on drug clearance, should be determined,
      because drug clearance is enhanced in patients receiving automated peritoneal
      dialysis, compared with those receiving CAPD, and also in those with urine
      output, compared to anuric patients. In addition, when residual renal function is
      impaired in CAPD patients with urine output, the decreased drug clearance must be
      compensated for by introducing a weekly hemodialysis treatment in some cases.
      Thus, careful consideration should be exercised in cases where drugs that have
      adverse effects on renal function are being administered, such as drugs that
      exert nephrotoxic effects and cause renal ischemia in CAPD patients. In the case
      of CAPD-related peritonitis, when an antibiotic that binds strongly to a protein
      is intravenously injected, the drug concentration in the peritoneal dialysate is
      low because only the unbound drug can be transported to the peritoneal dialysate.
      For this reason, when drugs, such as teicoplanin, that bind strongly to a protein
      are administered to CAPD patients with peritonitis, an intraperitoneal route is
      preferable to an intravenous route.

PMID- 22613913
TI  - Surgical and medical treatments of encapsulation peritoneal sclerosis.
AB  - Encapsulating peritoneal sclerosis (EPS) is a serious complication of long-term
      peritoneal dialysis (PD). The mortality rate for EPS has been high, primarily
      because of complications related to bowel obstruction. However, recent advances
      in clinical research have established the pathogenesis and course and a treatment
      strategy. To date, there is no consensus on therapy but care should be taken in
      trials using corticosteroid medication, and tamoxifen still remains controversial
      with respect to EPS treatment. The final therapeutic option for EPS is surgical
      enterolysis (adhesiolysis), and we have performed 239 surgical procedures in 181
      patients and observed favorable outcomes. In the 1990s, Japan experienced a large
      number of EPS cases, and PD therapy faced a crisis. There were many negative
      viewpoints on treatment of EPS at the beginning, but surgery became accepted in
      the face of an increasing number of cases, and several other facilities
      introduced surgical therapy. This activity promoted the understanding of, and
      countermeasures against, EPS in Japan, and EPS is no longer recognized as a fatal
      complication.

PMID- 22613914
TI  - Application of peritoneal dialysis in elderly patients by classifying the age
      into young-old, old, and oldest-old.
AB  - BACKGROUND: A greater number of end-stage renal disease patients are receiving
      peritoneal dialysis (PD) or hemodialysis (HD) in Japan. However, medical concerns
      with advancing age have been raised in PD utilization for elderly patients. The
      objective of this study was to address the indications for PD in elderly patients
      in terms of medical concerns such as nutrition state, residual renal function,
      dialysis efficiency, peritonitis, cardiovascular disease (CVD) complications, and
      technique survival. METHODS: In a retrospective, two-center study, we evaluated
      247 patients who newly started PD from 2002 to 2008. All patients were divided
      into four groups: young (<64 years, n = 99), young-old (65-74 years, n = 55), old
      (75-84 years, n = 62) and oldest-old (>=85 years, n = 31). Serum albumin,
      hemoglobin, beta(2)-microglobulin, cardio-thoracic ratio, 24-hour urine
      collection and spent dialysate volume was collected at the initiation of PD and
      after 1, 2, 3, and 4 years. PD withdrawal, occurrence of CVD complications,
      peritonitis and death were recorded. RESULTS: Nephrosclerosis as a primary
      disease increased with advancing age (p = 0.001). At baseline, gender, body
      weight, serum creatinine, hemoglobin and cardio-thoracic ratio were significantly
      different among the four groups. No significant decrease was shown in urine
      output with advancing age. The spent dialysate volume was significantly lower
      (mean 3.8 liters/day) in the oldest-old group compared with the other groups (p =
      0.001). However, a smaller volume of PD fluid in the oldest-old group was not
      accompanied by a significantly higher serum beta(2)-microgloblin level compared
      with the other groups and there was no reason of PD withdrawal for underdialysis
      in the old and oldest-old groups. Neither the incidence of CVD complications nor
      that of peritonitis was increased with advancing age. There was no significant
      difference in technique survival rate excluding death between each group. These
      findings suggest that there are no medical concerns to avoid PD therapy in
      elderly end-stage renal disease patients.

PMID- 22613915
TI  - Maintenance of continuous ambulatory peritoneal dialysis in elderly patients.
AB  - In Japan, peritoneal dialysis (PD) remains the principal modality of home
      dialysis for the elderly although PD patients accounted for only 3.3% (n = 9,728)
      of the overall dialysis patient population. One of the preventing factors for
      introduction of PD in elderly patients is the Japanese public nursing care
      system. Besides, difficulties in the continuation of dialysis therapy will arise
      because of the progression of dementia as well as the decline in muscular
      strength, vigor, and physical strength of patients. In spite of these
      difficulties, some local dialysis centers tried to maintain and manage elderly
      dialysis patients at home by utilizing diverse social resources, in addition to
      obtaining the cooperation of care givers such as family members. In our hospital,
      approximately 40% of patients who started dialysis therapy have selected PD. To
      support patients on PD, several special forms of care are prepared: utilization
      of visiting nurse care or home-visit nursing care services, supply of information
      on renal failure and education to home-care support providers and welfare service
      facility staff members. In addition, modulation of PD therapy such as automated
      PD and hemodialysis and PD in combination is also properly prepared. Lastly, the
      organization of a team, including physicians, nurses, social workers and
      dietitians, and the construction of a centralized patient information management
      system are important for elderly patients who need dialysis therapy.

PMID- 22613916
TI  - Role of nurses in a continuous ambulatory peritoneal diagnosis outpatient clinic.
AB  - The relationship between nurses and peritoneal dialysis (PD) patients begins from
      the time of the selection of medical treatment for renal replacement therapy.
      There are various roles in this field that involve nurses, not only in providing
      technical guidance to patients but also in relaying dietary restrictions
      including those on fluid and diet, in providing information on public welfare for
      dialysis patients and in fostering interactions between the patient and doctors,
      nutritionists, social workers and medical support staff. The nurse plays an
      important role in the success of a PD training program. Only highly trained
      nurses should carry out PD training. The nurse trains the patient or a family
      member as a helper to perform PD. The ultimate goal is to make a plan to help the
      patient maintain his or her general condition and expand the quality of life by
      self-care. However, the most important role of nurses is to display empathy to
      the patient, that is, to put themselves in the patient's position, to foster an
      ongoing interaction between themselves and the patient and to listen to the
      patient and understand what is in the mind of the patient.

PMID- 22613917
TI  - Combination therapy with hemodialysis and peritoneal dialysis.
AB  - Both continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) have
      their advantages regarding the treatment of patients with renal failure. In CAPD,
      solute removal is sometimes insufficient in patients who have a relatively large
      muscle mass that produces high levels of creatinine. To compensate for this
      deficiency, frequent exchanges and large peritoneal dialysate volumes are
      required. Alternatively, CAPD and HD as a combined modality of treatment for
      patients needing dialysis therapy has been proposed. Our experiences with three
      groups of patients are described. First, in 2003, 7 cases (6 males and 1 female;
      average age 54.3 +/- 4.5 years; mean duration of CAPD therapy 4.3 +/- 1.1 years;
      average weekly creatinine clearance (WCC) was 45.2 +/- 1.7 l/1.73 m(2)) were
      treated with once-a-week HD therapy (3.5 h; 200 ml/h). Addition of once-a-week HD
      therapy improved WCC to 66 +/- 7.1 liters/1.73 m(2). This improvement was due not
      only to the addition of HD therapy but also to an increase in creatinine
      clearance for 3 consecutive days after the completion of once-a-week HD therapy.
      Both creatinine clearance and ultrafiltration were significantly increased. Other
      clinical parameters such as blood pressure control, weight control, and dosage of
      erythropoietin were significantly improved after introducing this therapy.
      Second, we followed 9 CAPD patients who underwent an additional weekly HD for
      more than 3 years. Similar improvements were obtained in this long-term study as
      seen in the short-term study. Besides, the incidence of peritonitis decreased
      dramatically from 0.13 to 0.09 episodes/patient-year (p < 0.05) during the 3-year
      study. These data suggest that the combined use of CAPD and HD improves solute
      clearance in CAPD patients who are insufficiently dialyzed. Third, based on these
      data, we examined the efficacy of an early start of combination therapy and found
      that it stabilized dialysis therapy and prolonged the duration of CAPD. Combined
      with several of the previous several reports and our present experience, it is
      suggested that an early start of HD therapy will prolong the survival rate in
      patients on CAPD with physically stable conditions.

PMID- 22613918
TI  - Implementation of a cooperative program for peritoneal dialysis.
AB  - Nephrologists and dialysis specialists familiar with renal replacement therapies
      (RRTs) should periodically send appropriate information to chronic kidney disease
      (CKD) patients from the early stage via a cooperation program and educate
      patients on choosing a suitable RRT themselves. From 2009 to 2010, 63 patients
      (32 men and 31 women) were introduced to our hospital by a general practitioner
      through a cooperation program. Five patients (7.9%) measured home blood pressure
      and 2 (3.2%) received nutrition education. On close inspection, 7 patients
      (11.1%) had undergone surgery for cancer or a severe cardiovascular disease. We
      changed the prescription contents of the general practitioners in 58 patients
      (92.1%) and gave nutrition education to the 61 patients (96.8%) who did not
      receive it. In the 57 patients (90.5%) who continued the cooperation program, we
      changed the prescription contents of 32 patients (56.1%), and all patients
      recorded home blood pressure on the second visit. Participation in the
      educational peritoneal dialysis (PD) promotion program enabled advanced-stage CKD
      patients to understand PD, and as a result, PD selectivity at our hospital
      increased from 8.8 to 15.0% over 2 years. Periodic intervention of specialists in
      the cooperation program is necessary to assess values of parameters such as blood
      pressure, blood glucose, lipids, uric acid, and anemia during the clinical course
      to delay the progression of CKD. It is important that PD patients improve their
      quality of life by continuing treatment to prevent deterioration of residual
      renal function as much as possible after PD initiation in the same manner as CKD
      predialysis.

PMID- 22613919
TI  - Care for patients carrying out dialysis therapy at home.
AB  - The goal of home dialysis is to more successfully reintegrate dialysis patients
      with high activities in daily life (ADL) into society as compared to hemodialysis
      (HD), which is carried out at a dialysis facility. By achieving this goal, this
      therapy can prove to be more effective than renal plantation, which has been
      carried out only in a few cases in Japan. Since self-management forms the basis
      of home dialysis, dialysis complications can be reduced by arranging meals, fluid
      management and dialysis schedule according to the lifestyle of the patient
      himself. In addition, long-term survival rate with health conditions similar to
      that of a healthy person can be increased. On the other hand, the goal of home
      dialysis for dialysis patients with a lower ADL is to strengthen the family bond,
      and improve quality of life and life prognosis, since nursing and support from
      family members are essential to ensure a long-term survival rate and ADL. For
      safe operation of home dialysis, which can be more effective than HD carried out
      in dialysis facilities, it is important for doctors, nurses, clinical engineers,
      social workers and all other members of the dialysis staff to work together as a
      united team. The type of nursing varies depending on period (during conservative
      treatment of end-stage renal disease, during the introduction and maintenance of
      dialysis, and when changing to end-stage renal disease replacement therapy). It
      also varies depending on whether continuous ambulatory peritoneal dialysis or
      home hemodialysis is implemented. The important points of nursing in home
      dialysis for each treatment period, depending on whether by continuous ambulatory
      peritoneal dialysis and home hemodialysis, are summarized here.

PMID- 22613920
TI  - Perspectives on home hemodialysis in Japan.
AB  - Home hemodialysis (HHD) started in Japan in 1969. It has been done in the largest
      number of patients with the purpose of better social reintegration, followed by
      patients for whom commuting to a hospital is geographically difficult. In a
      subanalysis of the JSDT patient registry, the survival rate at 9 years for male
      patients excluding those with diabetes was significantly better in HHD patients
      than in facility dialysis patients. This result was thought to indicate that HHD
      was superior treatment both medically and socially, but it has not increased
      greatly because of conditions that impede the implementation of HHD, such as
      finding a caregiver and the burden on the caregiver, as well as the burden of
      light, heat, and water costs. However, long-duration dialysis and frequent
      dialysis are done even in general dialysis treatment, and the number of HHD
      patients has increased recently because of some improvement in health insurance
      payments for HHD in 1998. The spread of HHD is essential also in the broad
      implementation of diversifying HD modalities, and maintaining an accurate
      registry of HHD patients, analyzing factors that affect survival rates with each
      modality, clarifying conditions for adequacy of dialysis, and clarifying which
      treatments are superior are important future issues for dialysis treatment.

PMID- 22613921
TI  - Current international status of home hemodialysis.
AB  - Three times weekly home hemodialysis (HHD) was introduced shortly after the
      initiation of chronic hemodialysis (HD) treatment in 1960. HHD eliminates the
      need of transportation to and from the dialysis unit and by allowing patients to
      set their own dialysis schedule, decreases the burden of treatment on their
      personal and professional lives. HHD has been found more economical and more
      highly associated with better patient survival than in-center dialysis.
      Nevertheless, the global prevalence of HHD decreased between 1980 and 2000 due to
      the increased availability of dialysis units and continuous ambulatory peritoneal
      dialysis, advances in cadaveric kidney transplantation, and several other
      factors. However, the availability of HHD at a frequency of more than 3
      times/week, the typical frequency of conventional HD (CHD), in such forms as
      brief HD sessions of 2-3 h 5-6 days/week and nocturnal HD (NHD) has led to
      reversals in this trend. Frequent HHD, such as short daily HD (SDHD) and NHD
      instead of 3 times/week CHD, has been found to significantly improve
      hypertension, left ventricular mass, renal anemia, quality of life and mortality.
      On the other hand, NHD has been found to significantly improve hypertension, left
      ventricular mass, renal anemia, quality of life, malnutrition, mortality and
      phosphate clearance. Many observational clinical studies and one randomized
      controlled trial of SDHD and/or NHD have been conducted, and compact and
      convenient dialysis machines have been developed and used for HHD. The most
      recent data reported in the national and local registries of selected countries
      indicate that the prevalence of HHD among all dialysis patients from 2008 to 2010
      varied from 0 to 3.3% except in New Zealand and Australia, where it was 16.3 and
      9.3%, respectively. As HHD appears to be a more effective and economical dialysis
      modality than in-center CHD, its prevalence is likely to increase in the future.

PMID- 22613922
TI  - Future home hemodialysis - advantages of the NxStage System One.
AB  - To improve the quality of life (QOL) of patients with renal failure who are on
      dialysis, we have been working to promote home hemodialysis (HHD), but it has not
      come into widespread use at present because of various problems, including
      limitations of the equipment, the large proportion of elderly patients, and
      difficulty performing self-care. With regard to problems with the equipment,
      dialysis equipment for home use has not yet been approved in Japan, so equipment
      designed for medical facilities has to be used for home dialysis. Such equipment
      is bulky and occupies living space, as well as involving the cost of home
      renovation and the need for a caregiver. The NxStage System One (NSO) artificial
      kidney has served advantages for HHD compared with conventional equipment, since
      it is compact, portable, and easy to operate (especially for preparation and
      cleaning), does not require a water supply, occupies less living space, and
      reduces the need for renovation of the home. Other advantages of the NSO include
      improvement of QOL by saving time travelling to hospitals and helping patients to
      participate in social activities. In addition, HHD with the NSO can improve sleep
      disorders, the restless legs syndrome, and depressive symptoms, resulting in a
      good outcome. Moreover, HHD with the NSO reduces the need for drugs, such as
      antihypertensive medications and erythropoietin, possibly leading to saving of
      healthcare costs.

PMID- 22613923
TI  - Introduction to home hemodialysis.
AB  - The advantages of home hemodialysis (HHD) are the high degree of freedom in
      treatment, as well as that both long- and short-duration dialyses are possible.
      The main characteristic of HHD may be its diversity. Vital prognosis is also
      good. HHD is thought to lead to improvements in nutritional state, physical and
      mental state, and vital prognosis. This is the direction in which we would like
      to take HHD. HHD has a large role to play in a time such as today when better
      quality of life is sought.

PMID- 22613924
TI  - Overnight home hemodialysis: eight patients and six years of experience in
      Sakairumi clinics.
AB  - We started our home hemodialysis (HHD) program in July 2005 and have been
      promoting overnight HHD. As more than 6 years have passed since we started our
      HHD program, we review our HHD program and 8 overnight HHD patients (5 males and
      3 females). Their underlying disease differs in each and none have diabetic
      nephropathy. Their average age was 49.2 +/- 6.0 years (mean +/- SD). Average
      duration of dialysis treatment, HHD, and overnight HHD was 9.4 +/- 4.4, 3.5 +/-
      2.4, and 2.2 +/- 1.7 years, respectively. Average treatment time per dialysis
      session was 6.9 +/- 0.8 h/treatment, average treatment days weekly was 4.5 +/-
      0.8 days/week, and average treatment time weekly was 31.2 +/- 7.0 h/week.
      Laboratory data were good and their blood pressure was well controlled without
      any antihypertensive drugs excluding a patient who was recently introduced to
      dialysis with some residual kidney function. Severe problems did not occur in
      these 6 years except for blood access infection twice, slipping out of a needle
      during dialysis with small blood loss once, and a drop in blood pressure at the
      end of dialysis once, which was recovered by her assistant's help. According to
      our HHD training program, the average training duration for HHD was 106 +/- 42
      days. The shortest was 60 days and longest 198 days. These differences among
      training durations might be because of the frequency of training and having a
      better hand of puncturing. We did not instruct any additional issues and points
      for overnight HHD, because performing overnight HHD is similar to standard HHD.
      Some patients moved to overnight HHD slowly starting with once weekly and the
      others started overnight HHD several days after they had started HHD.

PMID- 22613925
TI  - Practice of home hemodialysis in dialysis clinic.
AB  - The number of dialysis patients in Japan was approximately 300,000 at the end of
      2010. Among these patients, however, the number of those undergoing home
      hemodialysis (HHD) was only 279 (<0.1 %). It is clear that HHD is a superior
      treatment to in-center hemodialysis, because of the unlimited frequency and time
      of HHD, as well as its association with a higher QOL and greater improvement in
      complications (e.g. hypertension). However, there are still many challenges to be
      overcome in order to disseminate HHD. It has yet to become widely available,
      partially because of low-level recognition among dialysis patients and healthcare
      workers providing dialysis, rather than problems regarding medical technologies
      and the economy. Of the 16 HHD patients in this center, 10 are practicing
      overnight hemodialysis, and they are extremely satisfied with its advantages:
      prolonged treatment yields a better health condition, the dialysis time seems
      shorter than 1 h by practicing it during hours that include the sleeping time,
      their complexion becomes as favorable as that of healthy persons, their itchy
      sensation resolves, they feel as if their physical conditions have returned to a
      normal level, and their QOL surprisingly increases. Training for HHD is conducted
      in the dialysis unit along with other patients receiving dialysis treatment
      (three times a week). Such training lasts for approximately 3 months, during
      which time patients continue their work. After the initiation of HHD at home,
      patients and their caregivers can contact our center staff with a cellular phone
      at any time so they do not need to feel anxious. We hope that many patients will
      practice HHD in order to resume an active daily life.

PMID- 22613926
TI  - Perspective of home hemodialysis in Japan.
AB  - HHD is one of the ESRD therapies that has been established after more than 35
      year's experience in Japan. However, only 279 patients were treated with HHD in
      2010, which accounts for 0.1% of 297,000 dialysis patients. Long-term HD has been
      popular in Japanese dialysis units because of the education and enlightenment by
      some enthusiastic nephrologists who understand the advantage of slow and long
      dialyses. Following excellent clinical outcomes from Tassin County in France and
      the DOPPS study has revealed that long and frequent hemodialyses result in good
      clinical outcomes. These findings have encouraged Japanese nephrologists to
      promote intensive hemodialysis treatment in their HD units, and HHD has become
      the focus of dialysis methods. This review describes the training and practical
      procedures of HHD in Japan. The barriers of HHD use are discussed from patient
      related and medical system-related viewpoints.

PMID- 22613927
TI  - Role of clinical engineers in home hemodialysis.
AB  - Compared to conventional hemodialysis (HD), home hemodialysis (HHD) enables
      marked increases in HD duration and frequency. Better clinical outcomes have been
      reported for HHD, including improvements in patient survival and their quality of
      life. However, statistical analysis by the Japanese Society for Dialysis Therapy
      in 2010 revealed that only 0.1% of the end-stage renal disease patients received
      HHD in Japan. In our hospital, clinical engineers as well as doctors and nurses
      have resolutely been working towards the education, maintenance and management of
      HHD. More than 30 patients have successfully and safely started HHD within the
      last 3 years. To carry out HHD, a certain amount of knowledge is required to
      understand the principles of dialysis and clinical engineering and how to use HD
      devices. About 50% of the problems during HHD were related to HD devices. Thus,
      we feel that it is essential to extend HHD so that clinical engineers can
      systematically structure and support HHD.

PMID- 22613928
TI  - Daily hemodialysis improves uremia-associated clinical parameters in the short
      term.
AB  - Observational studies suggest that home hemodialysis (HHD) is associated with
      improvements in several important clinical parameters. These include better
      control of blood pressure, reductions in left ventricular hypertrophy, calcium
      phosphate production, improved nutritional status and enhanced health-related
      quality of life. In Japan, many case reports and studies of small series of
      patients treated with HHD have been published mainly in Japanese. The current
      study was to describe the short-term effects in patients starting HHD at the
      Kidney Disease Center, Saitama Medical University. This study represents a
      comprehensive evaluation of the benefits of switching patients from conventional
      in-center hemodialysis to HHD in Japan. The pertinent findings are as follows: an
      improvement in blood pressure control paralleled with a reduction in
      antihypertensive pharmacotherapy an improvement in serum albumin and hemoglobin
      levels, and a simultaneous reduction in erythropoietin-stimulating agent, calcium
      and phosphate levels. In conclusion, our study confirms that selected patients
      may benefit from HHD which offers an attractive treatment alternative and
      improvements provided by HHD might ultimately have an impact On patient Survival.

PMID- 22613929
TI  - Development of a nanotechnology-based dialysis device.
AB  - Over 300,000 patients who need renal replacement therapy in our country are
      struggling to cope with daily life restrictions and complications because of
      dialysis therapy. They have to spend 3 half days a week for hemodialysis therapy
      which accounts for 95% of all renal replacement therapies in Japan. Moreover,
      they also have to be afraid of many complications associated with dialysis.
      Although these complications mostly arise from the shortage of dialysis quantity,
      we have been unable to improve the hemodialysis therapy system using
      extracorporeal circulation. Recently, we clinically investigated long-term
      dialysis therapies - one was a home-dialysis system and the other a portable
      dialysis system. We have also developed a very small dialysis device using
      nanotechnology, considering an implantable artificial kidney instead of
      transplantation in the near future.

PMID- 22613930
TI  - Guidelines for histopathological specimen examination and diagnostic reporting of
      primary bone tumours.
AB  - This review is intended to provide histopathologists with guidelines for
      clinical assessment, specimen handling and diagnostic reporting of benign and
      malignant primary bone tumours.  Information from radiology, surgical, oncology
      and other clinical colleagues involved in the diagnosis and treatment of primary
      bone tumours should be properly assessed before undertaking a structured approach
      to specimen handling and histological reporting. This  ensures that the
      information needed for planning appropriate treatment of these complex tumours is
      provided.  Consistency in diagnostic evaluation with respect to both terminology
      and report content facilitates liaison at multidisciplinary bone tumour meetings
      and collaboration between cancer units and networks, as well as providing a
      common database for audit of the clinical, radiological and pathological aspects
      of bone tumours.

PMID- 22613933
TI  - Prostate cancer: Heavy water labelling could be used to monitor progression of
      low-risk prostate cancer.

PMID- 22613931
TI  - New insights into the health effects of dietary saturated and omega-6 and omega-3
      polyunsaturated fatty acids.
AB  - Cardiovascular diseases and cancers are leading causes of morbidity and
      mortality. Reducing dietary saturated fat and replacing it with polyunsaturated
      fat is still the main dietary strategy to prevent cardiovascular diseases,
      although major flaws have been reported in the analyses supporting this approach.
      Recent studies introducing the concept of myocardial preconditioning have opened
      new avenues to understand the complex interplay between the various lipids and
      the risk of cardiovascular diseases. The optimal dietary fat profile includes a
      low intake of both saturated and omega-6 fatty acids and a moderate intake of
      omega-3 fatty acids. This profile is quite similar to the Mediterranean diet. On
      the other hand, recent studies have found a positive association between omega-6
      and breast cancer risk. In contrast, omega-3 fatty acids do have anticancer
      properties. It has been shown that certain (Mediterranean) polyphenols
      significantly increase the endogenous synthesis of omega-3 whereas high intake of
      omega-6 decreases it. Finally, epidemiological studies suggest that a high omega
      3 to omega-6 ratio may be the optimal strategy to decrease breast cancer risk.
      Thus, the present high intake of omega-6 in many countries is definitely not the
      optimal strategy to prevent cardiovascular disease and cancers. A moderate intake
      of plant and marine omega-3 in the context of the traditional Mediterranean diet
      (low in saturated and omega-6 fatty acids but high in plant monounsaturated fat)
      appears to be the best approach to reduce the risk of both cardiovascular
      diseases and cancers, in particular breast cancer.

PMID- 22613934
TI  - Urinary incontinence: Connexin43--clocking bladder rhythms in mice.

PMID- 22613932
TI  - MicroRNAs as putative mediators of treatment response in prostate cancer.
AB  - MicroRNAs (miRNAs) are an abundant class of noncoding RNAs that function to
      regulate post-transcriptional gene expression, predominantly by translational
      repression. In addition to their role in prostate cancer initiation and
      progression, recent evidence suggests that miRNAs might also participate in
      treatment response across a range of therapies including radiation treatment,
      chemotherapy and androgen suppression. The mechanism of this regulation is
      thought to be multifactorial and is currently poorly understood. To date, only a
      small number of studies have examined the functional role of miRNAs in response
      to prostate cancer treatment. Elucidating the role of miRNAs in treatment
      response following radiotherapy, chemotherapy and androgen suppression will
      provide new avenues of investigation for the development of novel therapies for
      the treatment of prostate cancer.

PMID- 22613935
TI  - Total talar fracture - inter- and intra-observer reproducibility of two
      classification systems (Hawkins and AO) for central talar fractures.
AB  - INTRODUCTION: We evaluated the inter- and intra-observer reproducibility of two
      classification systems for central talar fractures (Hawkins, as modified by Canal
      and Kelly and then by us; AO/AOT). HYPOTHESIS: The analysis and classification of
      these fractures will be better with CT scans than with X-rays. MATERIAL AND
      METHODS: Four observers evaluated 39 X-ray and CT scan files twice in the span of
      six weeks; each evaluation entailed classifying the fractures and describing
      their main features. Cohen's Kappa coefficient for inter-rater agreement was
      calculated and analysed. RESULTS: The inter- and intra-observer reproducibility
      with CT scans was better with X-rays for most of the parameters evaluated. The
      modified Hawkins classification provided better reproducibility than the AO/AOT
      one. However, this classification system was not perfect, even after
      modifications and use of CT scans. DISCUSSION: CT scans are an essential tool for
      the analysis of all talar fractures. We modified the Hawkins classification (as
      modified by Canal and Kelly) to include a Type 0 (no displacement or less than
      2mm), include frontal body fractures that are displaced like neck fractures and
      take into account comminuted fractures and other trauma in the area. LEVEL OF
      PROOF: IV - retrospective clinical study.

PMID- 22613936
TI  - Poor results of the OptetrakTM cemented posterior stabilized knee prosthesis
      after a mean 25-month follow-up: analysis of 110 prostheses.
AB  - INTRODUCTION: The introduction of a new knee arthroplasty model, even if it
      differs from a validated implant by only a few details, should be followed by
      rigorous assessment. The OptetrakTM cemented posterior stabilized knee prosthesis
      evolved from the Insall prosthesis with a smaller tibial keel associated with a
      higher tibial cam and increased femorotibial congruency as well as a more
      posterior-stabilized trochlea. HYPOTHESIS: We hypothesized that this implant with
      only minor modifications to the Insall prosthesis would provide as favorable
      results as the Insall prosthesis. MATERIALS AND METHODS: A continuous series of
      110 prostheses (106 patients) implanted between 2005 and 2007 was retrospectively
      analyzed with a mean follow-up of 25 months (range, 12-42 months) by an
      independent observer. The follow-up was based on the IKS score and the
      radiological assessment was conducted by three senior surgeons. RESULTS: The mean
      IKS score was 83.7 (range, 13-100) points at the last follow-up, the mean
      function score was 82.6 (range, 30-100 points), and mean flexion was 120 degrees 
      (range, 80-140 degrees ). Seventeen patients (15%) were disappointed or
      dissatisfied, 25 knees (22%) were painful, requiring regular painkillers. The
      prostheses had a satisfactory mechanical axis, with a mean HKA angle of 177.4 +/-
      4 degrees , but 25 prostheses (22%) presented rims evolving toward tibial implant
      loosening, and 24 (21%) developed signs of patellofemoral conflict. With follow
      up less than 5 years, nine cases were revised for tibial loosening, three for
      patellofemoral instability, and one for patellofemoral pain. The cases of tibial
      loosening were particular because they occurred at the cement-tibial-implant
      interface. The cumulated survival rate at 36 months was 80.97 +/- 9.1% and 76.74
      +/- 12% at 45 months. DISCUSSION: This tibial implant with a small keel does not
      resist the stresses applied by posterior stabilization, with notably a higher
      level of stress than the Insall prosthesis from which it was derived. In cases of
      centering defect, the design of the trochlea can lead to impingement between the
      edges of the patella and the prominent edges of the prosthetic trochlea. We have
      suspended implantation of this prosthesis and continue to monitor the progression
      of patients having received these implants. LEVEL OF EVIDENCE: Level IV,
      retrospective study.

PMID- 22613937
TI  - A maximum likelihood QTL analysis reveals common genome regions controlling
      resistance to Salmonella colonization and carrier-state.
AB  - BACKGROUND: The serovars Enteritidis and Typhimurium of the Gram-negative
      bacterium Salmonella enterica are significant causes of human food poisoning.
      Fowl carrying these bacteria often show no clinical disease, with detection only
      established post-mortem. Increased resistance to the carrier state in commercial
      poultry could be a way to improve food safety by reducing the spread of these
      bacteria in poultry flocks. Previous studies identified QTLs for both resistance
      to carrier state and resistance to Salmonella colonization in the same White
      Leghorn inbred lines. Until now, none of the QTLs identified was common to the
      two types of resistance. All these analyses were performed using the F2 inbred or
      backcross option of the QTLExpress software based on linear regression. In the
      present study, QTL analysis was achieved using Maximum Likelihood with QTLMap
      software, in order to test the effect of the QTL analysis method on QTL
      detection. We analyzed the same phenotypic and genotypic data as those used in
      previous studies, which were collected on 378 animals genotyped with 480 genome
      wide SNP markers. To enrich these data, we added eleven SNP markers located
      within QTLs controlling resistance to colonization and we looked for potential
      candidate genes co-localizing with QTLs. RESULTS: In our case the QTL analysis
      method had an important impact on QTL detection. We were able to identify new
      genomic regions controlling resistance to carrier-state, in particular by testing
      the existence of two segregating QTLs. But some of the previously identified QTLs
      were not confirmed. Interestingly, two QTLs were detected on chromosomes 2 and 3,
      close to the locations of the major QTLs controlling resistance to colonization
      and to candidate genes involved in the immune response identified in other,
      independent studies. CONCLUSIONS: Due to the lack of stability of the QTLs
      detected, we suggest that interesting regions for further studies are those that
      were identified in several independent studies, which is the case of the QTL
      regions on chromosomes 2 and 3, involved in resistance to both Salmonella
      colonization and carrier state. These observations provide evidence of common
      genes controlling S. Typhimurium colonization and S. Enteritidis carrier-state in
      chickens.

PMID- 22613938
TI  - Fecal calprotectin concentrations in premature infants have a lower limit and
      show postnatal and gestational age dependence.
AB  - BACKGROUND: There is a need for reliable diagnostic biomarkers in necrotizing
      enterocolitis (NEC). Whereas fecal calprotectin (fCP) has been reported to have
      insufficient sensitivity and specificity, no previous study has stratified for
      gestational and postnatal age. OBJECTIVE: We aimed to provide developmental
      specific fCP data in premature infants and to analyze its value in detecting
      intestinal distress and episodes of NEC. METHODS: Between April 2008 and December
      2009, 1,899 fecal samples were obtained from 206 very low birth weight infants.
      RESULTS: Mean gestational age (GA) was 28.5 weeks and birth weight 1,057 g. 19
      (9.2%) patients developed NEC stage II+, of whom 5 had fulminant NEC with
      unusually low fCP concentrations in meconium and afterwards. fCP levels showed
      significant gestational and postnatal age dependent dynamics with particularly
      low levels in extremely premature infants. In infants with a GA <26 + 1 weeks
      using GA-adapted reference values, the sensitivity for discriminating moderate
      NEC from healthy infants and infants with intestinal distress was 0.89 for a cut
      off of 180 and 210 ug/g, respectively, at onset of symptoms. Specificity was 0.96
      and 0.84. Fulminant NEC was characterized by unusually low fCP concentrations
      with a cut-off of <24 ug/g having a sensitivity of 0.84 and a specificity of 0.72
      for identifying those cases. CONCLUSIONS: fCP levels depend on gestational and
      postnatal age and in contrast to adults, there is a lower limit in premature
      infants. Taking these observations into account when defining reference values
      and interpreting fCP data in the clinical context, fCP can be a useful marker in
      identifying premature infants with gastrointestinal distress and NEC in
      particular.

PMID- 22613939
TI  - The E/e' ratio in the gray zone as predictor of left atrial dysfunction in
      patients with normal left ventricular ejection fraction: a speckle tracking
      study.

PMID- 22613940
TI  - Development and validation of criterion-referenced clinically relevant fitness
      standards for maintaining physical independence in later years.
AB  - PURPOSE: To develop and validate criterion-referenced fitness standards for older
      adults that predict the level of capacity needed for maintaining physical
      independence into later life. The proposed standards were developed for use with
      a previously validated test battery for older adults-the Senior Fitness Test
      (Rikli, R. E., & Jones, C. J. (2001). Development and validation of a functional
      fitness test for community--residing older adults. Journal of Aging and Physical
      Activity, 6, 127-159; Rikli, R. E., & Jones, C. J. (1999a). Senior fitness test
      manual. Champaign, IL: Human Kinetics.). METHODS: A criterion measure to assess
      physical independence was identified. Next, scores from a subset of 2,140
      "moderate-functioning" older adults from a larger cross-sectional database,
      together with findings from longitudinal research on physical capacity and aging,
      were used as the basis for proposing fitness standards (performance cut points)
      associated with having the ability to function independently. Validity and
      reliability analyses were conducted to test the standards for their accuracy and
      consistency as predictors of physical independence. RESULTS: Performance
      standards are presented for men and women ages 60-94 indicating the level of
      fitness associated with remaining physically independent until late in life.
      Reliability and validity indicators for the standards ranged between .79 and .97.
      IMPLICATIONS: The proposed standards provide easy-to-use, previously unavailable
      methods for evaluating physical capacity in older adults relative to that
      associated with physical independence. Most importantly, the standards can be
      used in planning interventions that target specific areas of weakness, thus
      reducing risk for premature loss of mobility and independence.

PMID- 22613941
TI  - Direct and indirect effects of religiosity on valuation of life through
      forgiveness and social provisions among older incarcerated males.
AB  - PURPOSE OF THE STUDY: Few studies have investigated the influence of religiosity
      (REL), forgiveness, and social resources on incarcerated individuals' attachment
      to their lives, or valuation of life (VOL). We tested a model linking REL to VOL
      through 3 subscales of the Heartland Forgiveness Scale (Self, Others, and
      Situations) and social provisions (SPS). DESIGN AND METHODS: Cross-sectional data
      were collected from 261 male prison inmates, aged 45-82, incarcerated in 8 state
      managed correctional facilities. Participants were sampled from the prison census
      database (Oklahoma Department of Corrections or DOC). Exclusion criteria, per the
      Oklahoma DOC, were those housed in medical or psychiatric units, currently in
      solitary confinement, or sentenced to death row. RESULTS: To account for possible
      violations of multivariate normality, we used the Satorra-Bentler chi-square
      statistic. The final model fit the data well, explaining 57% of the variance in
      VOL: chi(2) (N = 261; df = 3) = 7.40; p = .06; Comparative Fit Index = .99; root
      mean squared error of approximation = .08; standardized root mean squared
      residual = .02. Significant indirect effects of REL on VOL were present through
      Forgiveness of Others and SPS, and of REL on SPS through Forgiveness of Others.
      Analyses controlled for age, race, education, perceived physical health, and
      depressive symptoms. IMPLICATIONS: Implications of the findings for those
      involved with prisoner care are discussed, particularly therapeutic interventions
      including process models of forgiveness.

PMID- 22613943
TI  - Mobility after traumatic brain injury: relationships with ankle joint power
      generation and motor skill level.
AB  - BACKGROUND: Reduced balance, spasticity, contractures, muscle weakness, and motor
      skill levels may all contribute to mobility limitations after traumatic brain
      injury (TBI), yet the key physical impairments that contribute to mobility
      limitations remain unclear. OBJECTIVE: The aim of this study was to determine
      which physical impairments best predict mobility performance after a period of 6
      months of rehabilitation. PARTICIPANTS: Participants with TBI were selected if
      they were receiving therapy for mobility limitations but were able to walk
      without physical assistance. OUTCOME MEASURES: The clinical assessment included
      measures of balance, spasticity, and contracture, and 3-dimensional quantitative
      gait analysis was used to quantify joint power generation and motor skill level
      on 31 adults with severe TBI. Mobility outcome was quantified with the high-level
      mobility assessment tool. RESULTS: Two variables, ankle joint power generation
      during the push-off phase of gait and motor skill level, explained 66.5% of the
      variability in mobility outcome. Balance, strength, and mobility performance, all
      improved significantly over the 6 months of rehabilitation. Only 2 participants
      had contractures, which affected mobility. Balance disorders were prevalent and
      improved with rehabilitation, yet they contributed to only a limited extent to
      the level of recovery in mobility. CONCLUSION: Ankle joint power generation at
      push-off was the strongest predictor of mobility outcome after 6 months of
      rehabilitation in ambulant people with TBI.

PMID- 22613945
TI  - Hypothalamic-pituitary dysfunction following traumatic brain injury affects
      functional improvement during acute inpatient rehabilitation.
AB  - OBJECTIVE: To evaluate the occurrence of hypothalamic-pituitary dysfunction
      following a traumatic brain injury (TBI) and to determine its effect on
      functional improvement in acute inpatient rehabilitation. METHODS: A
      retrospective chart review identified male patients with a primary diagnosis of
      TBI with or without a skull fracture, an onset date within 6 months prior to
      admission, and were 16 years of age or older. The percentage of individuals in
      this population with abnormal hormone levels was determined on the basis of the
      established normal reference range for each hormone assay. The functional
      independence measure, which assesses functional outcomes in acute inpatient
      rehabilitation, was used to examine the relationship between hormone levels and
      functional improvement. RESULTS: Hypothalamic-pituitary dysfunction was
      identified in nearly 70% of men following TBI. Hypogonadism, or low testosterone
      levels, was observed in 66% of the patients, followed by low levels of free T4 in
      46% and low levels of insulin growth factor-1 in 26% of patients. Hypopituitarism
      associated with impaired functional recovery. Specifically, the functional
      independence measure change per day was significantly lower in patients with low
      levels of testosterone and insulin growth factor-1. CONCLUSIONS: These findings
      suggest the importance of testosterone and insulin growth factor-1 activity in
      the early stages of physical and cognitive rehabilitation.

PMID- 22613942
TI  - Modulation of excitability, membrane currents and survival of cardiac myocytes by
      N-acylethanolamines.
AB  - N-acylethanolamines (NAE) are endogenously produced lipids playing important
      roles in a diverse range of physiological and pathological conditions. In the
      present study, using whole-cell patch clamp technique, we have for the first time
      investigated the effects of the most abundantly produced NAEs, N
      stearoylethanolamine (SEA) and N-oleoylethanolamine (OEA), on electric
      excitability and membrane currents in cardiomyocytes isolated from endocardial,
      epicardial, and atrial regions of neonatal rat heart. SEA and OEA (1-10MUM)
      attenuated electrical activity of the myocytes from all regions of the cardiac
      muscle by hyperpolarizing resting potential, reducing amplitude, and shortening
      the duration of the action potential. However, the magnitudes of these effects
      varied significantly depending on the type of cardiac myocyte (i.e., endocardial,
      epicardial, atrial) with OEA being generally more potent. OEA and to a lesser
      extent SEA suppressed in a concentration-dependent manner currents through
      voltage-gated Na(+) (VGSC) and L-type Ca(2+) (VGCC) channels, but induced
      variable cardiac myocyte type-dependent effects on background K(+) and Cl(-)
      conductance. The mechanisms of inhibitory action of OEA on cardiac VGSCs and
      VGCCs involved influence on channels' activation/inactivation gating and partial
      blockade of ion permeation. OEA also enhanced the viability of cardiac myocytes
      by reducing necrosis without a significant effect on apoptosis. We conclude that
      SEA and OEA attenuate the excitability of cardiac myocytes mainly through
      inhibition of VGSCs and VGCC-mediated Ca(2+) entry. Since NAEs are known to
      increase during tissue ischemia and infarction, these effects of NAEs may mediate
      some of their cardioprotective actions during these pathological conditions.

PMID- 22613944
TI  - Examining acute rehabilitation outcomes for children with total functional
      dependence after traumatic brain injury: a pilot study.
AB  - OBJECTIVE: To examine in a pilot cohort factors associated with functional
      outcome at discharge and 3-month follow-up after discharge from inpatient
      rehabilitation in children with severe traumatic brain injury (TBI) who entered
      rehabilitation with the lowest level of functional skills. PARTICIPANTS: Thirty
      nine children and adolescents (3-18 years old) who sustained a severe TBI and had
      the lowest possible rating at rehabilitation admission on the Functional
      Independence Measure for Children (total score = 18). METHODS: Retrospective
      review of data collected as part of routine clinical care. RESULTS: At discharge,
      59% of the children were partially dependent for basic activities, while 41%
      remained dependent for basic activities. Initial Glasgow Coma Scale score, time
      to follow commands, and time from injury to rehabilitation admission were
      correlated with functional status at discharge. Time to follow commands and time
      from injury to rehabilitation admission were correlated with functional status at
      3-month follow-up. Changes in functional status during the first few weeks of
      admission were associated with functional status at discharge and follow-up.
      CONCLUSIONS: Even children with the most severe brain injuries, who enter
      rehabilitation completely dependent for all daily activities, have the potential
      to make significant gains in functioning by discharge and in the following few
      months. Assessment of functional status early in the course of rehabilitation
      contributes to the ability to predict outcome from severe TBI.

PMID- 22613946
TI  - Acute assessment of brain injuries in ground-level falls.
AB  - OBJECTIVE: The purpose of this study was to characterize traumatic brain injuries
      (TBI) sustained in ground-level falls (GLFs). The focus was on factors associated
      with acute computed tomographic (CT) findings. METHODS: The sample included 575
      subjects examined and treated at the Tampere University Hospital emergency
      department (ED). Retrospective data collection consisted of subject- and injury
      related data and clinical information from the emergency department. All CT scans
      were analyzed and systematically coded. RESULTS: Ground-level falls were the
      mechanism of injury in 48.3% (n = 278) of the subjects. In the GLF group,
      independent risk factors for acute traumatic CT findings were long-term alcohol
      abuse, older age, being found on the ground, and left temporoparietal and
      occipital location of direct head impact. There were no significant differences
      in the incidence of any intracranial traumatic lesion type between those with
      GLFs and other causes of TBI. None of the classic clinical TBI severity markers
      studied were associated with acute traumatic CT findings in patients with GLFs.
      CONCLUSIONS: Older age and long-term alcohol abuse increase the likelihood of
      acute intracranial CT abnormalities. The pattern of intracranial traumatic CT
      findings does not differ from other causes of TBI. Clinical signs and indices of
      TBI severity did not predict traumatic CT findings.

PMID- 22613947
TI  - Efficacy of amantadine treatment on symptoms and neurocognitive performance among
      adolescents following sports-related concussion.
AB  - OBJECTIVE: To evaluate the efficacy of amantadine in the treatment of symptoms
      and neurocognitive performance in adolescents following sports-related
      concussion. PARTICIPANTS: A clinical sample of 25 male (n = 11) and female (n =
      14) adolescent subjects with an age-, sex-, and concussion history-matched group
      of 25 male (n = 11) and female (n = 14) control subjects. SETTING: Outpatient
      concussion clinic. INTERVENTION: Retrospective, case-control design. Treatment
      group consisted of patients treated with 100 mg of amantadine twice daily (200 mg
      total per day) following a period of rest. Matched controls were evaluated and
      treated conservatively without medication at the same concussion program prior to
      the start of the current amantadine protocol. MAIN OUTCOME MEASURES: Immediate
      Postconcussion Assessment and Cognitive Test computerized neurocognitive test
      battery and symptom report. RESULTS: Results support significantly greater
      improvements from pre- to posttest in reported symptoms, verbal memory, and
      reaction time performance for the amantadine group than the matched controls.
      There were no significant differences for visual memory or visual motor
      processing speed. CONCLUSION: This study provides empirical support for
      amantadine as an effective pharmacologic treatment of certain concussion-related
      cognitive deficits and symptoms in athletes with protracted recovery of more than
      3 weeks.

PMID- 22613950
TI  - NLRC5: a NOD-like receptor protein with many faces in immune regulation.

PMID- 22613951
TI  - What comes first: translational repression or mRNA degradation? The deepening
      mystery of microRNA function.
AB  - While many mechanisms have been proposed for microRNAs (miRNAs) function, most
      ultimately cause message degradation. A view has emerged that miRNAs silence gene
      expression by promoting the association of mRNA decay factors. Recent research
      results, however, suggest that in both zebrafish and fruit fly, translational
      inhibition is the initiating event of miRNA-mediated gene silencing.

PMID- 22613949
TI  - Determination of synthetic lethal interactions in KRAS oncogene-dependent cancer
      cells reveals novel therapeutic targeting strategies.
AB  - Oncogenic mutations in RAS genes are very common in human cancer, resulting in
      cells with well-characterized selective advantages, but also less well-understood
      vulnerabilities. We have carried out a large-scale loss-of-function screen to
      identify genes that are required by KRAS-transformed colon cancer cells, but not
      by derivatives lacking this oncogene. Top-scoring genes were then tested in a
      larger panel of KRAS mutant and wild-type cancer cells. Cancer cells expressing
      oncogenic KRAS were found to be highly dependent on the transcription factor
      GATA2 and the DNA replication initiation regulator CDC6. Extending this analysis
      using a collection of drugs with known targets, we found that cancer cells with
      mutant KRAS showed selective addiction to proteasome function, as well as
      synthetic lethality with topoisomerase inhibition. Combination targeting of these
      functions caused improved killing of KRAS mutant cells relative to wild-type
      cells. These observations suggest novel targets and new ways of combining
      existing therapies for optimal effect in RAS mutant cancers, which are
      traditionally seen as being highly refractory to therapy.

PMID- 22613952
TI  - REV-ERB-erating nuclear receptor functions in circadian metabolism and
      physiology.
AB  - A hallmark of the mammalian circadian timing system is synchronization of
      physiology and behavior, but when this synchronization is disturbed, chronic
      diseases such as metabolic syndrome and depression may develop. Three new studies
      show that nuclear receptors of the Rev-Erb family impact the circadian oscillator
      and its metabolic output and this can be modified with specific agonists. Hence,
      resynchronization of metabolic pathways by manipulation of the circadian
      oscillator using REV-ERB-specific agonists may represent a feasible therapeutic
      concept to target diseases rooted in a misaligned circadian system.

PMID- 22613953
TI  - A universal activator of microRNAs identified from photoreaction products.
AB  - A small molecule activator of microRNAs has been identified from photoreaction
      products of naphthalene-1,4-dione with acetylenes and the universal activation on
      miRNAs was realized through significant promotion on the processing of precursor
      microRNAs by the compound.

PMID- 22613954
TI  - Bioactivity of nanostructure on titanium surface modified by chemical processing
      at room temperature.
AB  - PURPOSE: Recently, there has been considerable interest in finding novel
      applications and functions for existing dental materials. We found that, at room
      temperature and atmospheric pressure, titanium oxide spontaneously generates
      nanostructures very similar to the "nanotubes" created by TiO(2) sputtering. The
      aim of this study was to evaluate the ability of this surface to affect the
      cellular osteogenic differentiation response. METHODS: Titanium disks without and
      with a 'nanosheet' deposited on their surface were used as the control and test
      groups, respectively. Cell culture experiments were performed with SD rat bone
      marrow cells, which were seeded into microplate wells and cultured in media
      designed to induce osteogenic differentiation. We measured alkaline phosphatase
      (ALP) activity, osteocalcin (OCN) production, calcium deposition and Runx2 gene
      expression to assess the levels of differentiation. RESULTS: After 14 and 21
      days, cellular ALP activity was significantly higher in the test group than in
      the control group. After 28 days, cells in the test group also showed
      significantly more calcium deposition and OCN production than those in the
      control group. There was significantly different expression of Runx2 mRNA in the
      test group compared to the control group after 3 days of culture. CONCLUSION: In
      conclusion, these data suggest that titanium implants modified by the application
      of nanostructures promote osteogenic differentiation, and may improve the
      biointegration of these implants into the alveolar bone.

PMID- 22613955
TI  - Gender difference in masticatory performance in dentate adults.
AB  - PURPOSE: To clarify whether there might be a gender difference in masticatory
      performance in dentate adults. METHODS: Thirty male subjects and thirty female
      subjects were asked to chew gummy jelly on their habitual chewing side for 10, 15
      and 20s and the amounts of glucose extraction were measured. The changes of both
      glucose extraction and standardized glucose extraction from 10 to 20s were
      investigated differently for males and females. The amount of glucose extraction
      was compared between males and females for each chewing duration. In addition, in
      order to confirm a gender difference in occlusal force, the maximum occlusal
      force was compared between males and females. RESULTS: For both males and
      females, the amount of glucose extraction was lowest for 10-s chewing and
      increased significantly for 15-s and 20-s chewing. The mean standardized glucose
      extraction values increased in proportion with the duration of chewing. The
      standard deviations of the standardized glucose extraction were very small (below
      0.02) for all chewing durations in both males and females. With regard to
      comparison of the glucose extraction between males and females, the amount of
      glucose extraction was significantly larger for males than for females for all
      chewing durations. The maximum occlusal force was significantly larger for males.
      CONCLUSION: It was suggested that it might be important to take into
      consideration gender-related differences while analyzing masticatory performance
      in dentate adults.

PMID- 22613956
TI  - Influence of microthreads and platform switching on stress distribution in bone
      using angled abutments.
AB  - PURPOSE: To evaluate the stress distribution in peri-implant bone by simulating
      the effect of an implant with microthreads and platform switching on angled
      abutments through tridimensional finite element analysis. The postulated
      hypothesis was that the presence of microthreads and platform switching would
      reduce the stress concentration in the cortical bone. METHODS: Four mathematical
      models of a central incisor supported by an implant (5.0 mm * 13 mm) were created
      in which the type of thread surface in the neck portion (microthreaded or smooth)
      and the diameter of the angled abutment connection (5.0 and 4.1mm) were varied.
      These models included the RM (regular platform and microthreads), the RS (regular
      platform and smooth neck surface), the SM (platform switching and microthreads),
      and the SS (platform switching and smooth neck). The analysis was performed using
      ANSYS Workbench 10.0 (Swanson Analysis System). An oblique load (100N) was
      applied to the palatine surface of the central incisor. The bone/implant
      interface was considered to be perfectly integrated. Values for the maximum
      (sigma(max)) and minimum (sigma(min)) principal stress, the equivalent von Mises
      stress (sigma(vM)), and the maximum principal elastic strain (E(max)) for
      cortical and trabecular bone were obtained. RESULTS: For the cortical bone, the
      highest sigma(max) (MPa) were observed for the RM (55.1), the RS (51.0), the SM
      (49.5), and the SS (44.8) models. The highest sigma(vM) (MPa) were found for the
      RM (45.4), the SM (42.1), the RS (38.7), and the SS models (37). The highest
      values for sigma(min) were found for the RM, SM, RS and SS models. For the
      trabecular bone, the highest sigma(max) values (MPa) were observed in the RS
      model (6.55), followed by the RM (6.37), SS (5.6), and SM (5.2) models.
      CONCLUSION: The hypothesis that the presence of microthreads and a switching
      platform would reduce the stress concentration in the cortical bone was partially
      rejected, mainly because the microthreads increased the stress concentration in
      cortical bone. Only platform switching reduced the stress in cortical bone.

PMID- 22613957
TI  - A colorimetric probe for the selective naked-eye detection of Pb(II) ions in
      aqueous media.
AB  - A new colorimetric molecular probe based on a 4,4-difluoro-4-bora-3a,4a-diaza-s
      indacene (BODIPY) dye selectively binds Pb(II) ions in aqueous solutions,
      allowing for highly sensitive naked-eye detection.

PMID- 22613958
TI  - Customized chemotherapy based on epidermal growth factor receptor mutation status
      for elderly patients with advanced non-small-cell lung cancer: a phase II trial.
AB  - BACKGROUND: Elderly patients are more vulnerable to toxicity from chemotherapy.
      Activating epidermal growth factor receptor (EGFR) mutations in non-small-cell
      lung cancer (NSCLC) are associated with enhanced response to EGFR tyrosine-kinase
      inhibitors. We studied patients with advanced NSCLC for whom treatment was
      customized based on EGFR mutation status. METHODS: We screened 57 chemotherapy
      naive patients with histologically or cytologically confirmed NSCLC, stage IIIB
      or IV, aged 70 years or older, and with an Eastern Cooperative Oncology Group
      performance status 0 or 1, for EGFR exon 19 codon 746-750 deletion and exon 21
      L858R mutation. Twenty-two patients with EGFR mutations received gefitinib; 32
      patients without mutations received vinorelbine or gemcitabine. The primary
      endpoint was the response rate. RESULTS: The response rate was 45.5% (95%
      confidence interval [CI]: 24.4%, 67.8%) in patients with EGFR mutations and 18.8%
      (95% CI: 7.2%, 36.4%) in patients without EGFR mutations. The median overall
      survival was 27.9 months (95%CI: 24.4 months, undeterminable months) in patients
      with EGFR mutations and 14.9 months (95%CI: 11.0 months, 22.4 months) in patients
      without EGFR mutations. In the gefitinib group, grade 3/4 hepatic dysfunction and
      dermatitis occurred in 23% and 5% of patients, respectively. In patients treated
      with vinorelbine or gemcitabine, the most common grade 3 or 4 adverse events were
      neutropenia (47%; four had febrile neutropenia), anemia (13%), and anorexia (9%).
      No treatment-related deaths occurred. CONCLUSIONS: Treatment customization based
      on EGFR mutation status deserves consideration, particularly for elderly patients
      who often cannot receive second-line chemotherapy due to poor organ function or
      comorbidities. TRIAL REGISTRATION: This trial is registered at University
      hospital Medical Information Network-clinical trial registration
      (http://www.umin.ac.jp/ctr/index/htm) with the registration identification number
      C000000436.

PMID- 22613959
TI  - Dipicolylamine as a unique structural switching element for helical peptides.
AB  - Developing novel methods for metal-induced switching of peptide structures
      expands the design principles of functional biomolecules and biomaterials. Here,
      a simple method for on-resin synthesis of dipicolylamine (Dpa)-containing
      peptides was developed. Whereas addition of divalent metal ions such as Fe(ii)
      and Cu(ii) to a peptide bearing a pair of Dpa moieties at the i and i + 4
      positions led to the formation of a 1:1 complex of Dpa with metals, addition of
      Ni(ii) yielded a cross-linked structure of Dpa-metal (2:1). This feature was
      utilized for the selective detection of Ni(ii) using the peptide-Fe(ii) complex.
      Repeated switching of the helical structure was also achieved by multiple
      additions of divalent metal ions to the peptide.

PMID- 22613960
TI  - Depolarization potentiates TRAIL-induced apoptosis in human melanoma cells: role
      for ATP-sensitive K+ channels and endoplasmic reticulum stress.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is promising for
      cancer treatment owing to its selective cytotoxicity against malignant cells.
      However, some cancer cell types, including malignant melanoma cells, are
      resistant to TRAIL-induced apoptosis. Therefore, drugs that can amplify TRAIL
      cytotoxicity are urgently required. Depolarization of the plasma membrane
      potential is associated with apoptosis induced by a variety of death-inducing
      agents but its role in apoptosis remains a matter of debate. We found that TRAIL
      treatment resulted in robust depolarization in human melanoma cells with a
      considerable lag (2-4 h). Moreover, membrane-depolarizing agents, including K+
      and ATP-sensitive K+ (KATP) channel inhibitors glibenclamide and U37883A enhanced
      TRAIL-induced apoptosis. On the contrary, inhibitors of calcium- and voltage
      dependent K+ channels and mitochondrial KATP channels had no such effects.
      Melanocytes were insensitive to TRAIL-induced depolarization and apoptosis as
      well as to the sensitization by membrane-depolarizing agents despite their
      substantial surface expression of death receptors. TRAIL induced robust
      activation of X-box-binding protein-1 and caspase-12, both of which were enhanced
      by the K+ and KATP channel inhibitors, but not by other K+ channel inhibitors.
      Finally, caspase-12-selective inhibitor completely abolished the amplification of
      apoptosis. These findings suggest that depolarization promotes endoplasmic
      reticulum stress-mediated death pathway, thereby amplifying TRAIL cytotoxicity.
      Thus, membrane-depolarizing agents such as KATP channel inhibitors may have
      therapeutic potential in the treatment of TRAIL-resistant cancer cells without
      impairing tumor-selectivity.

PMID- 22613961
TI  - Comparison of Doppler-based and three-dimensional methods for fetal cardiac
      output measurement.
AB  - OBJECTIVE: Fetal cardiac output is conventionally measured using two-dimensional
      (2D) and Doppler ultrasound (Doppler). New methods based on 3D measurements of
      ventricular size in systole and diastole have been proposed. Our aim was to
      validate these tools against the conventional Doppler-based methods. METHODS:
      Fetal combined cardiac output was prospectively measured at 16, 20, and 24 weeks
      of gestation in 15 uncomplicated pregnancies using Doppler and three different 3D
      algorithms [virtual organ computer-aided analysis (VOCAL), sonographic automatic
      volume calculation (SonoAVC), and inversion mode]. We determined the inter- and
      intraobserver variability of the 3D techniques and assessed the correlation
      between Doppler and 3D. RESULTS: The 3D techniques showed adequate inter- and
      intraobserver reproducibility (intraclass correlation coefficient 0.69-0.98),
      with the best reproducibility for SonoAVC and inversion mode. Bland-Altman
      analysis revealed low bias and relatively good correlations when comparing the 3D
      methods among each other, albeit with wide 95% confidence intervals. Doppler
      measurement of fetal weight-adjusted combined cardiac output (349.0 ml.min-1.kg
      1) yielded significantly higher results than 3D CO measurements (177.2, 160.7,
      and 174.0 ml.min-1.kg-1 for VOCAL, SonoAVC, and inversion mode, respectively; p <
      0.0001) and correlated poorly with the 3D methods. CONCLUSIONS: Although 3D
      volume-based cardiac output measurements are reproducible, results obtained with
      different methods are not interchangeable. SonoAVC and inversion have the highest
      intra- and interobserver reproducibility. Results of cardiac output measurement
      by 3D and Doppler cannot be interchanged.

PMID- 22613962
TI  - Genetic influences on vitamin D status and forearm fracture risk in African
      American children.
AB  - We sought to investigate the relationship between newly identified genetic
      variants and vitamin D levels and fracture risk in healthy African American
      (black) children. This case-control study included children of both sexes, ages 5
      to 9 years, with and without forearm fractures. Serum 25-hydroxy vitamin D
      levels, bone mineral density, body mass index, and calcium/vitamin D intake were
      measured in 130 individuals (n = 60 cases and n = 70 controls). The 5 variants
      tested were located in the GC gene (rs2282679), in the NADSYN1 gene (rs12785878
      and rs3829251), and in the promoter region of the CYP2R1 gene (rs2060793 and
      rs104741657). Associations between single nucleotide polymorphisms (SNPs) and
      vitamin D levels were tested using an analysis of covariance. Associations
      between SNPs and fracture status were tested using logistic regression. The GC
      gene variant was associated with vitamin D levels (P = 0.038). None of the SNPs
      were associated with fracture status in young blacks. These results suggest that
      the variants tested, which are associated with circulating vitamin D levels in
      whites, are not associated with fracture status in healthy black children.
      Additional research is required to discover the genetics of fracture risk in
      blacks.

PMID- 22613963
TI  - Protective effect of transplanted bone marrow-derived mesenchymal stem cells on
      pancreatitis-associated lung injury in rats.
AB  - Severe acute pancreatitis (SAP) is initiated by the premature activation of
      digestive enzymes within the pancreatic acinar cells, leading to self-digestion
      and inflammatory responses in pancreatic ductal cells, thus giving rise to
      systemic inflammatory response syndrome (SIRS). The most common and serious SIRS
      is pancreatitis-associated lung injury, and inflammatory mediators play an
      important role in its pathogenesis. Bone marrow-derived mesenchymal stem cells
      (MSCs) are differentiated into alveolar endothelial cells to replace the damaged
      alveolar endothelial cells and inhibit inflammatory response in the injured lung
      tissues. In this study, we aimed to investigate the therapeutic effect of bone
      marrow-derived MSCs in rats with pancreatitis-associated lung injury.
      Experimental SAP was induced by a retrograde injection of 5% sodium taurocholate
      into the biliopancreatic duct of 75 male Sprague-Dawley rats, which were divided
      into the SAP group (n=25), the MSC group (n=25) and the sham-operated group
      (n=25) to explore the pathology and function of lung tissues and the regulation
      of inflammatory mediators. Pulmonary edema was estimated by measuring water
      content in the lung tissues. Pulmonary myeloperoxidase (MPO) activity was
      detected using spectrophotometry. Serum amylase was detected using the Automatic
      Biochemistry Analyzer. Tumor necrosis factor-alpha (TNF-alpha) and substance P
      (SP) mRNA levels were determined by quantitative reverse transcriptase-polymerase
      chain reaction. Our results showed that serum amylase activity was significantly
      decreased in the MSC group compared to the SAP group. Pulmonary edema was
      significantly diminished (p<0.05) in the MSC group compared to the SAP group.
      Typical acute lung injury was observed in the SAP group, and the pathological
      changes were mild in the MSC group. The expression of TNF-alpha and SP mRNA in
      lung tissue was diminished in the MSC group compared to the SAP group. In
      conclusion, MSC transplantation attenuates pulmonary edema and inflammation, and
      reduces the mRNA expression of TNF-alpha and SP in pancreatitis-associated lung
      injury.

PMID- 22613964
TI  - Cardiovascular autonomic imbalance and baroreflex dysfunction in the
      apolipoprotein E-deficient mouse.
AB  - Genetically engineered mouse models and advances in molecular biotechnology have
      given extensive aid to experimental studies of cardiovascular mechanisms and
      dysfunction in pathological states such as atherosclerosis. Among the available
      animal models that have been developed to study atherosclerosis, the
      apolipoprotein E-deficient (apoE(-/-)) mouse is the most ideal genetically
      modified animal presently available. The apoE(-/-)mouse develops spontaneous
      severe hypercholesterolemia in a short-time and subsequently develops
      atherosclerotic lesions similar to those found in humans. Since its creation two
      decades ago, the apoE(-/-)mouse has greatly contributed to the understanding of
      atherosclerosis, but the consequences of hypercholesterolemia and atherosclerosis
      for the autonomic control of cardiovascular function in this mouse model have not
      been reviewed. In this article, we provide an overview of abnormalities of the
      parasympathetic and sympathetic nervous systems controlling heart rate and blood
      pressure and emphasize the dysfunction of the baroreflex control of
      cardiovascular function and how this dysfunction is influenced by nitric oxide,
      reactive oxygen species, aging and an atherogenic diet in the apoE(-/-)mouse.

PMID- 22613965
TI  - The action of small GTPases Rab11 and Rab25 in vesicle trafficking during cell
      migration.
AB  - BACKGROUND: The closely related GTPases Rab11 and Rab25 promote cell migration by
      regulating vesicular transport and recycling of surface receptors. Rab25 carries
      a constitutively activating mutation in its GTPase domain. Increased expression
      of Rab25 has been associated with the aggressiveness of migrating tumor cells.
      Here, we aimed to elucidate potential differences in the role of those two
      GTPases in vesicle trafficking during cell migration. METHODS: We expressed Rab11
      and Rab25 wildtype and mutant constructs in HeLa and MDA-MB231 cells and measured
      their effect on cell morphology, vesicle dynamics and migration behaviour. In
      prostate cancer samples we analyzed the expression of both GTPases. RESULTS:
      Cells grown on fibronectin displayed a more stretched morphology when Rab11 was
      inactivated, whereas inactivation of Rab25 led to reduced stretching.
      Overexpression of both Rab11 and Rab25 accelerated cell migration. Analysis of
      vesicular movement revealed higher transport efficiency in the inner cell
      compartment for Rab11 positive vesicles and in proximity to the membrane for
      Rab25 positive vesicles. Interestingly, we found Rab25 to be highly expressed in
      prostate cancer tissue. CONCLUSION: Taken together, our data suggest that Rab11
      is mainly responsible for basal long-distance transport from the rear end to the
      front of the migrating cell, whereas Rab25 acts predominantly in the small-scale
      fast recycling within the tips of the cell. Our results further support the idea
      of Rab25 as a promoter of tumor development.

PMID- 22613966
TI  - NHE-1 relocation outside cholesterol-rich membrane microdomains is associated
      with its benzo[a]pyrene-related apoptotic function.
AB  - BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene
      (B[a]P), are ubiquitous toxic environmental pollutants capable of inducing cell
      death. Intracellular pH plays a key role in the regulation of cell survival and
      death. Our previous works have demonstrated that intracellular alkalinization
      mediated by Na(+)/H(+) exchanger 1 (NHE-1) is a critical event involved in B[a]P
      induced apoptosis. The aim of this study was to further elucidate the mechanisms
      of NHE-1 activation upon B[a]P exposure. METHODS: We tested the effects of plasma
      membrane cholesterol enrichment or depletion on B[a]P-induced NHE-1 activation
      related to apoptosis. We isolated cholesterol-rich plasma membrane microdomains
      to assess NHE-1 submembrane location and immunoprecipitated NHE-1 from the
      different sub-membrane fractions obtained to examine NHE-1 protein interactions
      during B[a]P-induced apoptosis. RESULTS: We found that NHE-1 is preferentially
      located in cholesterol-rich microdomains and that B[a]P activates NHE-1 via its
      relocation and binding of calmodulin outside these specialized plasma membrane
      microstructures; these events are necessary for the execution of the apoptosis
      related intracellular alkalinization. CONCLUSION: Plasma membrane location of NHE
      1 affects its protein interactions and apoptotic function.

PMID- 22613967
TI  - Mesothelioma cell proliferation through autocrine activation of PDGF-betabeta
      receptor.
AB  - BACKGROUND/AIMS: Growth factors play a critical role in proliferation for a
      variety of cancer cells. The present study was conducted to understand the
      signaling cascades underlying PDGF-D/PDGF-betabeta receptor-mediated
      proliferation of mesothelioma cells. METHODS: Cell growth and cell cycle were
      analyzed in human non-malignant Met5A cells and malignant mesothelioma cells such
      as MSTO-211H, NCI-H28, NCI-H2052, and NCI-H2452 cells. RESULTS: Growth of all the
      cells used here was not affected by PDGF-D, regardless of concentrations (1-30
      ng/ml) or treatment time (48-72 h). Spontaneous growth of those cells was
      significantly inhibited by knocking-down PDGFD or PDGF-betabeta receptor, without
      affecting cell cycling. The cell growth was significantly inhibited by the Akt
      inhibitor MK2206 and the ROCK inhibitor Y27632 for all the cell types, by the
      PDK1 inhibitor BX912 for NCI-H28 cells alone, and by the Rac1 inhibitor NSC23766
      for NCI-H2052 cells alone, while the PI3 kinase inhibitor wortmannin had no
      effect. The cell growth, alternatively, was significantly attenuated by MAP
      kinase kinase inhibitor PD98059 or the ERK1/2 inhibitor FR180204 for all the cell
      types. CONCLUSION: The results of the present study show that PDGF-D promotes
      mesothelioma cell proliferation by targeting ROCK or MAP kinase through autocrine
      activation of PDGF-betabeta receptor.

PMID- 22613968
TI  - The proliferative response of NB69 human neuroblastoma cells to a 50 Hz magnetic
      field is mediated by ERK1/2 signaling.
AB  - A number of studies have reported that extremely low frequency magnetic fields
      (ELF-MF) can modulate proliferative processes in vitro; however, the transduction
      mechanisms implicated in such phenomena remain to be identified. The present
      study was aimed to determine whether a 50 Hz, 100 MUT MF can induce cell
      proliferation in the human neuroblastoma line NB69, and whether the signaling
      pathway MAPK-ERK1/2 (Mitogen-Activated Protein Kinase - Extracellular-Signal
      Regulated Kinase 1 and 2) is involved in that proliferative response. The
      cultures were exposed intermittently or continuously to the MF for a 63-hour
      duration. The continuous treatment did not induce significant changes in cell
      proliferation. In contrast, intermittent exposure caused statistically
      significant increase in the percent of cells in phase S of the cell cycle,
      followed by a significant increase in cell number. The intermittent treatment
      also induced an early, transient and repetitive activation of ERK1/2 that could
      be involved in the proliferative effects. In fact, both the proliferative
      response and the repeated activation of ERK1/2 were blocked by PD98059, the
      specific inhibitor of MEK (ERK kinases 1 and 2). Taken together, the described
      results indicate that a 50 Hz, 100 MUT MF can stimulate proliferation in NB69
      cells by triggering MAPK-ERK1/ 2 signaling at each of the "On" periods of an
      intermittent exposure.

PMID- 22613969
TI  - Apoptosis-related gene transcription in human A549 lung cancer cells via A(3)
      adenosine receptor.
AB  - BACKGROUND/AIMS: Extracellular adenosine induces apoptosis in a variety of cancer
      cells via diverse signaling pathways. The present study investigated the
      mechanism underlying adenosine-induced apoptosis in A549 human lung cancer cells.
      METHODS: MTT assay, TUNEL staining, flow cytometry using propidium iodide and
      annexin V-FITC, real-time RTPCR, Western blotting, monitoring of mitochondrial
      membrane potentials, and assay of caspase-3, -8, and -9 activities were carried
      out in A549 cells, and the siRNA to silence the A(3) adenosine receptor-targeted
      gene was constructed. RESULTS: Extracellular adenosine induces A549 cell
      apoptosis in a concentration (0.01-10 mM)-dependent manner, and the effect was
      inhibited by the A3 adenosine receptor inhibitor MRS1191 or knocking-down A(3)
      adenosine receptor. Like adenosine, the A(3) adenosine receptor agonist 2-Cl-IB
      MECA also induced A549 cell apoptosis. Adenosine increased expression of mRNAs
      for Puma, Bax, and Bad, disrupted mitochondrial membrane potentials, and
      activated caspase-3 and -9 in A549 cells, and those adenosine effects were also
      suppressed by knocking-down A3 adenosine receptor. CONCLUSION: Adenosine induces
      A549 cell apoptosis by upregulating expression of Bax, Bad, and Puma, to disrupt
      mitochondrial membrane potentials and to activate caspase-9 followed by the
      effector caspase-3, via A(3) adenosine receptor.

PMID- 22613970
TI  - The Anx7(+/-) knockout mutation alters electrical and secretory responses to
      Ca(2+)-mobilizing agents in pancreatic beta-cells.
AB  - Insulin secretion from the pancreatic beta-cell is controlled by changes in
      membrane potential and intracellular Ca(2+). The contribution of intracellular
      Ca(2+) stores to this process is poorly understood. We have previously shown that
      beta-cells of mice lacking one copy of the Annexin 7 gene (Anx7(+/-)) express
      reduced levels of IP(3) receptors and defects in IP(3)-dependent Ca(2+)
      signaling. To further elucidate the effect of the Anx7(+/-) mutation on signaling
      related to intracellular Ca(2+) stores in the beta-cell, we measured the effects
      of Ca(2+) mobilizing agents on electrical activity, intracellular Ca(2+) and
      insulin secretion in control and mutant beta-cells. We found that the muscarinic
      agonist carbachol and the ryanodine receptor agonists caffeine and 4-chloro-m
      cresol had more potent depolarizing effects on Anx7(+/-) beta-cells compared to
      controls. Accordingly, glucose-induced insulin secretion was augmented to a
      greater extent by caffeine in mutant islets. Surprisingly, ryanodine receptor
      mediated Ca(2+) mobilization was not affected by the Anx7(+/-) mutation,
      suggesting that the mechanism underlying the observed differences in electrical
      and secretory responsiveness does not involve intracellular Ca(2+) stores. Our
      results provide evidence that both IP3 receptors and ryanodine receptors play
      important roles in regulating beta-cell membrane potential and insulin secretion,
      and that the Anx7(+/-) mutation is associated with alterations in the signaling
      pathways related to these receptors.

PMID- 22613971
TI  - Mesenchymal stem cell transplantation inhibits abnormal activation of
      Akt/GSK3beta signaling pathway in T cells from systemic lupus erythematosus mice.
AB  - Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized
      by activation and proliferation of autoreactive T cells and B cells. We examined
      changes in cell cycle progression of T cells from MRL/lpr mice with or without
      allogenic bone marrow mesenchymal stem cells (BMMSCs) treatment and analyzed the
      expression of cell cycle associated proteins. In addition, the Akt/GSK3beta
      protein kinase cascade was studied. We demonstrated that high-dose MSCs
      transplantation effectively ameliorated disease activity in MRL/lpr mice. BMMSCs
      treatment inhibited G1/S transition of the abnormal lupus T lymphocytes.
      Moreover, it increased the expression of p21(WAF1/CIP1) and p27(Kip1) and
      decreased the expression of CDK2. Furthermore, high-dose MSCs inhibited abnormal
      activation of the Akt/GSK3beta signaling pathway of T cells from MRL/lpr mice.
      Our results suggest that high-dose BMMSCs transplantation successfully treated
      MRL/lpr lupus mice by inhibiting abnormal activation of Akt/GSK3beta signaling
      pathway of T cells.

PMID- 22613972
TI  - Hypothyroidism modifies lipid composition of polymorphonuclear leukocytes.
AB  - Thyroid hormones are important regulators of lipid metabolism. Polymorphonuclear
      leukocytes (PMN) are essential components of innate immune response. Our goal was
      to determine whether hypothyroidism affects lipid metabolism in PMN cells. Wistar
      rats were made hypothyroid by administrating 0.1 g/L 6-propyl-2-thiouracil (PTU)
      in drinking water during 30 days. Triacylglycerides (TG), cholesterol and
      phospholipids were determined in PMN and serum by conventional methods. The mRNA
      expression of LDL receptor (LDL-R), 3-hydroxy-3-methylglutaryl-CoA reductase
      (HMGCoAR), sterol regulatory element binding protein 2 (SREBP-2), and
      diacylglycerol acyltransferase 2 (DGAT-2) were quantified by Real-Time PCR.
      Cellular neutral lipids were identified by Nile red staining. We found
      hypothyroidism decreases serum TG whereas it increases them in PMN. This result
      agrees with those observed in Nile red preparations, however DAGT-2 expression
      was not modified. Cholesterol synthesizing enzyme HMGCoAR mRNA and protein was
      reduced in PMN of hypothyroid rats. As expected, cholesterol content decreased in
      the cells although it increased in serum. Hypothyroidism also reduced relative
      contents of palmitic, stearic, and arachidonic acids, whereas increased the
      myristic, linoleic acids, and the unsaturation index in PMN. Thus, hypothyroidism
      modifies PMN lipid composition. These findings would emphasize the importance of
      new research to elucidate lipid-induced alterations in specific function(s) of
      PMN.

PMID- 22613973
TI  - Identification of cis-acting elements and signaling components of high affinity
      IgE receptor that regulate the expression of cyclooxygenase-2.
AB  - Allergic and inflammatory responses are functionally linked through a cascade of
      signaling events that connect the aggregation of the high affinity IgE receptor
      (FcepsilonRI) on mast cells and the initiation of cyclooxygenase-2 (COX-2)
      expression. In this study, we identified the cis-acting elements in the cox-2
      promoter that control the expression of COX-2 in RBL-2H3 mast cells. We also
      investigated how the inflammatory reaction is controlled by the allergic reaction
      by determining the signaling components employed by FcepsilonRI in the
      transcriptional regulation of cox-2. Among cis-acting components present in the
      cox-2 promoter, the CREB binding site, as well as the AP-1 and proximal NF-IL6
      binding sites to a lesser extent, were required for the transcriptional
      regulation of the cox-2 promoter. However, NF-kappaB and Ets-1 binding sites
      exerted negative effects on the cox-2 promoter activity. Among the signaling
      components of FcepsilonRI, Fyn, PI 3-kinase, Akt, and p38 MAPK positively
      mediated the COX-2 expression. Conventional PKCs and atypical PKCs exerted
      opposite regulatory effects on the cox-2 promoter activity. Blockade of MEK/ERK
      pathway inhibited the cox-2 promoter activity and the COX-2 expression. These
      results reveal intricate functional interactions among different cis-acting
      elements in the transcriptional regulation of cox-2. Fyn-->PI 3-kinase-->Akt
      pathway directly stimulate. On the other hand, Lyn-->Syk pathway exerts auxiliary
      or compensatory influences on COX-2 expression via PKC and MEK/ERK.

PMID- 22613974
TI  - Downregulation of ClC-2 by JAK2.
AB  - JAK2 (Janus kinase-2) is activated by cell shrinkage and may thus participate in
      cell volume regulation. Cell volume regulatory ion channels include the small
      conductance Cl(-) channels ClC-2. The present study thus explored whether JAK2
      influences ClC-2 activity. To this end, ClC-2 was expressed in Xenopus oocytes
      with or without wild type JAK2, active (V617F)JAK2 or inactive (K882E)JAK2 and
      the Cl(-) channel activity determined by dual electrode voltage clamp. Expression
      of ClC-2 was followed by a marked increase of cell membrane conductance. The
      conductance was significantly decreased following coexpression of JAK2 or
      (V617F)JAK2, but not by coexpression of (K882E)JAK2. Exposure of the oocytes
      expressing ClC-2 together with (V617F)JAK2 to the JAK2 inhibitor AG490 (40 MUM)
      resulted in a gradual increase of the conductance. According to chemiluminescence
      JAK2 decreased the channel protein abundance in the cell membrane. The decline of
      conductance in ClC-2 and (V617F)JAK2 coexpressing oocytes following inhibition of
      channel protein insertion by brefeldin A (5 MUM) was similar in oocytes
      expressing ClC-2 with (V617F)JAK2 and oocytes expressing ClC-2 alone, indicating
      that (V617F)JAK2 might slow channel protein insertion into rather than
      accelerating channel protein retrieval from the cell membrane. In conclusion,
      JAK2 down-regulates ClC-2 activity and thus counteracts Cl(-) exit, an effect
      which may impact on cell volume regulation.

PMID- 22613975
TI  - Mesangial medium from IgA nephropathy patients induces podocyte epithelial-to
      mesenchymal transition through activation of the phosphatidyl inositol-3
      kinase/Akt signaling pathway.
AB  - BACKGROUND: Podocyte injury plays an important role in glomerulosclerosis in IgA
      nephropathy (IgAN). Eepithelial-to-mesenchymal transition (EMT) caused by
      different factors is the main reason for podocyte damage. This study hypothesized
      that conditioned mesangial medium may induced EMT process of podocytes and
      thereby lead to glomerular injury or sclerosis. MATERIALS AND METHODS: Podocytes
      were incubated in medium from mesangial cells incubated with aggregated
      IgA1(aIgA1) isolated from IgAN patients. Wortmannin were used to inhibit
      phosphatidylinositol-3-kinase (PI3-K) in podocytes. RESULTS: Western blot
      analysis, real-time PCR and confocal fluorescent microscopy demonstrated that
      reduced expression of P-Cadherin, Zonula occludens-1 (ZO-1) and podocin,
      increased expression of fibroblast -specific protein (FSP-1), alpha-smooth muscle
      action(alpha-SMA) and desmin in podocytes exposed to medium from mesangial cells
      incubated with aIgA1 isolated from IgAN patients compared with podocytes cultured
      in RPMI 1640 medium containing 0.5% fetal bovine serum ( FBS) (p<0.05). Mesangial
      medium resulted in a greater albumin influx across the podocyte monolayer
      (p<0.05). Phosphorylation of Akt increased with this medium, as indicated by an
      increase in the p-Akt/Akt ratio. Treatment with wortmannin partly restored the
      changes in epithelial and mesenchymal markers and albumin influx. IgAN patients
      with massive proteinuria showed remarkable alpha-SMA and FSP-1 expression in
      podocytes. CONCLUSION: Our findings indicated that mesangial medium from cells
      incubated with aIgA1 isolated from IgAN patients induced EMT in podocytes and the
      PI3-K/ Akt-signaling pathway was involved in the process.

PMID- 22613976
TI  - Clara cell protein expression in human neonates during respiratory distress
      syndrome.
AB  - BACKGROUND/AIMS: Clara cell protein (cc-10) has been shown to negatively regulate
      inflammation, protect pulmonary surfactant from degradation in the lung, and
      administration of this recombinant protein improves the condition of infant
      respiratory distress syndrome (iRDS), a disease that occurred mainly in preterm
      infants. In view of the possibility that altered expression of cc-10 might
      regulate its protective function, we attempted to characterize this protein in
      infants with iRDS. METHODS: Using bronchotraqueal aspirates from human infants,
      we analyzed cc-10 in two-dimensional gel electrophoresis (2-DE) by combining
      immunoprecipitation, carbonyl groups and total protein immunoblotting. RESULTS:
      Seven forms of cc-10 were detected with western immunoblots in infants with iRDS
      while only four forms were present in neonates who needed mechanical ventilation
      for other reasons without any lung disease (control group). The overall levels of
      cc-10 in iRDS were lower and differences were seen in isoform pattern and
      distribution. CONCLUSION: Our demonstration that cc-10 is differentially
      expressed in infants with iRDS may point the way towards one possible mechanism
      that potentially involves modifications of the protein structure with its anti
      inflammatory and surfactant protective function and could be detrimental for this
      airway disorder.

PMID- 22613977
TI  - An inhibitory peptide derived from the alpha-subunit of the epithelial sodium
      channel (ENaC) shows a helical conformation.
AB  - Proteolytic activation of the heteromeric epithelial sodium channel (ENaC) is
      thought to involve the release of inhibitory peptides from the extracellular
      domains of its alpha- and gamma-subunit. Recently, we demonstrated that an alpha
      13-mer peptide, corresponding to a putative inhibitory region within the
      extracellular domain of human alphaENaC, inhibits human alphabetagammaENaC. The
      aim of the present study was to investigate the structural basis of the
      inhibitory effect of this alpha-13-mer peptide. Analysis of the peptide by
      replica exchange molecular dynamics method, circular dichroism spectroscopy,
      nuclear magnetic resonance spectroscopy, and molecular dynamics simulations
      suggested that a helical turn at the carboxy-terminus is the preferred
      conformational state of the alpha-13-mer peptide. From this we predicted that a
      specific mutation (leucine 188 to alanine) should have a strong effect on the
      conformational preferences of the peptide. To functionally test this, we compared
      the effect of the wild-type alpha-13-mer with that of a mutant alpha-L188A-13-mer
      on ENaC currents in Xenopus laevis oocytes heterologously expressing human
      alphabetagammaENaC. We demonstrated that replacing the leucine 188 by alanine
      abolished the inhibitory effect of the alpha-13-mer peptide on ENaC. These
      findings suggest that a helical conformation in its carboxyterminal part is
      functionally important to mediate ENaC inhibition by the alpha-13-mer peptide.
      However, high resolution structural information on the complex of the inhibitory
      alphaENaC peptide and the channel are needed to confirm this conclusion.

PMID- 22613979
TI  - Intratracheal instillation of lipopolymeric vectors and the effect on mice lung
      physiology.
AB  - BACKGROUND/AIMS: The current study compared the effects of intratracheal
      administration of different lipopolymeric vectors on lung function and histology
      in normal mice. METHODS: Forty-eight BALB/c mice were randomly divided into 8
      groups (6/group). All animals received intratracheal instillation of the
      following suspensions: polymerized [(A) 1,2-dimyristoyl-sn-glycero-3
      phosphocholine (DMPC):1,2-bis-(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine
      (DC8,9PC):1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), (B)
      DMPC:DC8,9PC:stearylamine (SA), (C) DMPC:DC8,9PC:myristoylcholine chloride
      (MCl)]; nonpolymerized [(D) DMPC:DC8,9PC:DOTAP, (E) DMPC:DC8,9PC:SA, (F)
      DMPC:DC8,9PC:MCl] together with plasmid DNA; vehicle (control), and pDsRed2-N1
      plasmid DNA (DNA). At 24 h, the survival rate, lung mechanics (resistive and
      viscoelastic pressure, static elastance) and morphometry were analyzed. RESULTS:
      The survival rate was 50% in D, 40% in E and F, and 100% in the CTRL, DNA, A, B
      and C groups. Animals from groups D, E, and F that died presented diffuse
      pulmonary hemorrhagic capillaritis. Lung mechanics, the fraction of normal and
      collapsed alveoli, as well as the number of polymorphonuclear and mononuclear
      cells in lung tissue were similar in all surviving mice. CONCLUSION:
      Intratracheal instillation of polymerized particles is safe compared with
      nonpolymerized formulations and may be used for future gene/drug therapy.

PMID- 22613978
TI  - Sildenafil acts as potentiator and corrector of CFTR but might be not suitable
      for the treatment of CF lung disease.
AB  - The phosphodiesterase-5 inhibitor sildenafil is an established and approved drug
      to treat symptoms of a variety of human diseases. In the context of cystic
      fibrosis (CF), a genetic disease caused by a defective CFTR gene (e.g. DeltaF508
      CFTR), it was assumed that sildenafil could be a promising substance to correct
      impaired protein expression. This study focuses on the molecular mechanisms of
      sildenafil on CFTR recovery. We used DeltaF508-CFTR/wt-CFTR expressing Xenopus
      laevis oocytes and human bronchial epithelial cell lines (CFBE41o(-)/16HBE14o(-))
      to investigate the pathways of sildenafil action. Cells were treated with
      sildenafil and cAMP-mediated current (I(m)), conductance (G(m)), and capacitance
      (C(m)) were determined. Sildenafil increased I(m), G(m), and C(m) of wt-CFTR and
      functionally restored DeltaF508-CFTR in oocytes. These effects were also seen in
      CFBE41o(-) and 16HBE14o(-) cells. Transepithelial measurements revealed that
      sildenafil mediated increase (wt-CFTR) and restoration (DeltaF508-CFTR) of
      channel activity. cGMP pathway blocker inhibited the activity increase but not
      CFTR/DeltaF508-CFTR exocytosis. From these data we conclude that sildenafil
      mediates potentiation of CFTR activity by a cGMP-dependent and initiates cGMP
      independent functional insertion of CFTR/DeltaF508-CFTR molecules into the apical
      membranes. Thus, sildenafil is a corrector and potentiator of CFTR/DeltaF508
      CFTR. Yet, the necessary high doses of the drug for CFTR recovery demonstrate
      that sildenafil might not be suited as a therapeutic drug for CF lung disease.

PMID- 22613980
TI  - Protective role of oligomycin against intestinal epithelial barrier dysfunction
      caused by IFN-gamma and TNF-alpha.
AB  - Although the precise mechanisms involved in intestinal barrier dysfunction
      induced by proinflammatory cytokines are incompletely understood, pharmacological
      restoration of barrier function is very important to the management of intestinal
      disease. This study was aimed to investigate the protective role of HIF-1alpha
      inhibitor oligomycin against intestinal epithelial barrier dysfunction induced by
      proinflammatory cytokines IFN-gamma and TNF-alpha, and the underlying mechanisms.
      To induce barrier dysfunction, Caco-2 monolayers were treated with IFN-gamma and
      TNF-alpha simultaneously. The cytokines-treated Caco-2 monolayers in the absence
      and in the presence of oligomycin were used for physiological, morphological, and
      biochemical analyses. The results showed that at the concentration of blocking
      HIF-1alpha activation, oligomycin significantly ameliorated TER reduction and
      paracellular permeability increase in Caco-2 monolayers challenged with IFN-gamma
      and TNF-alpha. Oligomycin also largely attenuated the IFN-gamma and TNF-alpha
      related relocalization of tight junction proteins ZO-1 and occludin. Western blot
      analysis revealed that oligomycin abolished the increases of both MLC
      phosphorylation and MLCK protein expression induced by IFN-gamma and TNF-alpha
      challenge. Quantitative RT-PCR analysis showed that oligomycin inhibited the IFN
      gamma and TNF-alpha-induced up-regulation of MLCK mRNA. It is concluded that
      oligomycin is able to attenuate intestinal epithelial barrier dysfunction induced
      by proinflammatory cytokines IFN-gamma and TNF-alpha. The mechanism by which
      oligomycin protects intestinal barrier function may, at least in part, be
      attributed to block the up-regulated MLCK transcription and protein expression
      induced by IFN-gamma and TNF-alpha.

PMID- 22613981
TI  - Overlapping cardiac phenotype associated with a familial mutation in the voltage
      sensor of the KCNQ1 channel.
AB  - BACKGROUND: Cardiac action potential repolarisation is determined by K(+)
      currents including I(Ks). I(Ks) channels are heteromeric channels composed of
      KCNQ1 and KCNE E-subunits. Mutations in KCNQ1 are associated with sinus
      bradycardia, familial atrial fibrillation (fAF) and/or short QT syndrome as a
      result of gain-of-function, and long QT syndrome (LQTS) due to loss-of-function
      in the ventricles. Here, we report that the missense mutation R231C located in S4
      voltage sensor domain is associated with a combined clinical phenotype of sinus
      bradycardia, fAF and LQTS. We aim to understand the molecular basis of the
      complex clinical phenotype. METHODS: We expressed and functionally analyzed the
      respective channels kinetics in Xenopus laevis oocytes. The molecular nature of
      the residue R231 was studied by homology modeling and molecular dynamics
      simulation. RESULTS: As a result, the mutation reduced voltage sensitivity of
      channels, possibly due to neutralization of the positive charge of the arginine
      side chain substituted by cysteine. Modeling suggested that the charge carrying
      side chain of R231 is positioned suitably to transfer transmembrane voltages into
      conformational energy. Further, the mutation altered the functional interactions
      with KCNE subunits. CONCLUSION: The mutation acted in a E-subunit dependent
      manner, suggesting I(Ks) function altered by the presence of different KCNE
      subunits in sinus node, atria and ventricles as the molecular basis of sinus
      bradycardia, fAF and LQTS in mutation carriers.

PMID- 22613982
TI  - In vitro model for assessing arrhythmogenic properties of drugs based on high
      resolution impedance measurements.
AB  - BACKGROUND/AIMS: Cardiac dysfunction is one of the main cause of drug candidate
      failures in the preclinical and/or clinical studies and responsible for the
      retraction of large number of drugs from the market. The prediction of arrhythmic
      risk based on preclinical trials during drug development remains limited despite
      intensive and costly investigation. Moreover, methods for analyzing beating
      behavior of cardiomyocytes (CMs) in culture to diagnose arrhythmias are not well
      developed. METHODS: In this study, we combined two emerging technologies, induced
      pluripotent stem (iPS) cell-derived CMs and impedance-based real-time
      (xCELLigence RTCA Cardio Instrument) monitoring of CM electrical activity, to
      assess the effect of drugs known affect cardiac activity such as isoproterenol,
      carbachol, terfenadine, sotalol and doxorubicin. Cells were exposed to a drug in
      a single dose or repeated dose scenarios and data were analyzed using RTCA Cardio
      software, Poincare plot and detrended fluctuation analysis. RESULTS: The results
      revealed significant changes in beating parameters of iPS-CMs induced by
      reference compounds. Heptanol, gap junction blocker, completely disrupted the
      synchronous beating pattern of iPS-CMs. Decrease of beating rate, amplitude and
      beat-to-beat signal variations of iPS-CMs monolayer observed in the presence of
      doxorubicin revealed severe abnormality detected by the system. Additionally, the
      irregular beating rhythms recorded in the presence of Terfenadine and Sotalol at
      high concentration, reflect abnormalities in cell contraction and/or relaxation
      which may lead to arrhythmia. CONCLUSIONS: All these results indicated that
      xCELLigence RTCA Cardio system combined with iPS cells, has the potential to be
      an attractive high-throughput tool for studying CMs during prolonged culture
      times and to screen potential drugs for cardiotoxic side effects.

PMID- 22613983
TI  - Spironolactone prevents aldosterone induced increased duration of atrial
      fibrillation in rat.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia in
      clinical practice. The Renin-Angiotensin-Aldosterone-System plays a major role
      for the atrial structural and electrical remodelling. Recently elevated
      aldosterone levels have been suggested to increase the risk for the development
      of AF. METHODS: Rats were treated with aldosterone by means of an osmotic
      minipump (0.5MUg/h) over a period of 4 weeks. AF was induced by transesophageal
      burst pacing. Action potentials (AP) were recorded from left atrial preparations
      with microelectrodes. Atrial collagen was quantified by histological studies.
      RESULTS: Aldosterone treatment resulted in hypertrophy as indicated by an
      increased ratio of heart weight/tibia length and doubled the time until the AF
      converted spontaneously into sinus rhythm (85.8+/-13.4 s vs. 38.3+/-6.9 s,
      p<0.01). This was associated with a significant shortening of the AP (APD90
      26.2+/-1.1 vs. 31.2+/-1.9, p<0.05) and an increased protein expression of Kir2.1
      and Kv1.5. Atrial collagen deposition was significantly greater in aldosterone
      treated rats. The alterations could be prevented by additional application
      spironolactone. CONCLUSIONS: The results of the present study suggest that in
      addition to the structural remodelling aldosterone also promotes AF by altering
      repolarising potassium currents leading to action potential shortening.

PMID- 22613985
TI  - MiR-106b and MiR-15b modulate apoptosis and angiogenesis in myocardial
      infarction.
AB  - BACKGROUND: MicroRNAs (miRNAs) are identified as crucial gene regulators in
      response to myocardial infarction (MI). However, the overall relationships
      between miRNAs and the gene targets which contribute to the cellular phenotypes
      in MI are not fully elucidated. To make a better understanding towards functional
      roles of miRNAs in MI, useful information was mined through bioinformatic
      techniques. METHOD: MI-related miRNAs were retrieved from publications, and
      PicTar, TargetScanS, and miRanda programs were used to predict their gene
      targets. Gene ontology (GO) and pathway analyses of gene targets were applied to
      uncover functional roles of miRNAs. The miRNA-gene networks were illustrated by
      Pajek tool. Finally, validation experiments were performed towards two important
      miRNAs in the networks. RESULT: Up to 119 MI-related miRNAs were retrieved from
      publications. GO and pathway analyses for their predicted gene targets
      demonstrated that these dysregulated miRNAs were enriched in cardiovascular
      related phenotypes. Through illustrating miRNA-gene networks, overall
      relationships between miRNAs and gene targets were detected especially in
      processes of apoptosis and angiogenesis. Moreover, experimental data supported
      bioinformatic predictions that miR-106b served as an anti-apoptotic modulator
      through inhibition of p21 expression and miR-15b displayed anti-angiogenesis
      activity. CONCLUSION: The miRNAs played essential roles in pathological processes
      of MI. Further, miR-106b and miR-15b maybe mediated as robust regulators in
      apoptosis or angiogenesis following MI, respectively.

PMID- 22613984
TI  - Direct renin inhibition exerts an anti-hypertrophic effect associated with
      improved mitochondrial function in post-infarction heart failure in diabetic
      rats.
AB  - BACKGROUND: In addition to hypertension control, direct renin inhibition has been
      shown to exert direct beneficial effects on the heart in post-infarction cardiac
      remodeling. This study elucidates the possible contribution of mitochondria to
      the anti-hypertrophic effects of the direct renin inhibitor aliskiren in post
      infarction heart failure complicated with diabetes in rats. METHODS: Diabetes was
      induced in male Sprague-Dawley rats by a single injection of streptozotocin (IP,
      65 mg/kg body weight). After 7 days, the animals were randomly assigned to 4
      groups: sham, heart failure, sham+aliskiren, and heart failure+aliskiren. Post
      infarction HF was induced by coronary artery ligation for 4 weeks. RESULTS:
      showed that heart failure reduced ejection fraction and cardiac output by 41%
      (P<0.01) and 42% (P<0.05), respectively, compared to sham-operated hearts.
      Cardiac dysfunction was associated with suppressed state 3 respiration rates and
      respiratory control index in mitochondria, and increased mitochondrial
      permeability transition pore (PTP) opening. In addition, heart failure reduced
      expression of the major mitochondrial sirtuin, SIRT3 and increased acetylation of
      cyclophilin D, a regulatory component of the PTP. Aliskiren significantly
      improved cardiac function and abrogated mitochondrial perturbations. CONCLUSION:
      Our results demonstrate that aliskiren attenuates post-infarction remodeling
      which is associated with its beneficial effects on mitochondria.

PMID- 22613986
TI  - Angiotensin II induces angiogenic factors production partly via
      AT1/JAK2/STAT3/SOCS3 signaling pathway in MHCC97H cells.
AB  - Angiotensin II (Ang II) has been shown to function as a key role in
      neovascularization of hepatocellular carcinoma (HCC), but little is known its
      underlying mechanisms. The aim of this study was to explore the role of Janus
      kinase/signal transducer and activator of transcription (JAK/STAT) signaling
      pathway in Ang II-induced HCC angiogenic factors production. Herein, we found
      that Ang II upregulated angiogenic factors production such as vascular
      endothelial growth factor (VEGF), angiopoietin-2 (Ang-2) and Tie-2 in MHCC97H
      cells in a time- and concentration-dependent manner. And VEGF and Ang-2 caused a
      significant increase in angiogenic tube formation. Especially, Ang II-induced
      angiogenic tube formation was blunted by VEGF small interfering RNA (siRNA) and
      Ang-2 siRNA, respectively. The JAK2 inhibitor AG490 partly attenuated the effects
      of Ang II. Moreover, Ang II- induced JAK2 and STAT3 phosphorylation was
      significantly suppressed by losartan but not PD123319. Meanwhile, STAT3
      phosphorylation and suppressor of cytokine signaling 3 (SOCS3) expression induced
      by Ang II were evidently impaired by AG490. More importantly, SOCS3 siRNA
      remarkably reinforced Ang II-induced VEGF, Ang-2 and Tie-2 generation in MHCC97H
      cells. Taken together, the present study demonstrates that Ang II induces
      angiogenic factors production partly via AT1/ JAK2/STAT3/SOCS3 signaling pathway
      in MHCC97H cells. These findings may provide important insights into the
      potential mechanism with respect to the AT1/ JAK2/ STAT3/SOCS3 signaling pathway
      associated with Ang II-induced angiogenesis in the pathogenesis of HCC.

PMID- 22613987
TI  - Panax notogingseng saponins suppress RAGE/MAPK signaling and NF-kappaB activation
      in apolipoprotein-E-deficient atherosclerosis-prone mice.
AB  - BACKGROUND: Panax notoginseng saponins (PNS) extracted from the roots of panax
      notoginseng are free radical-scavenger, with an antioxidant property, capable of
      inhibiting expression of adhesion molecules and chemokines. This study was
      designed to test the effects of PNS administration in apolipoprotein (apo)-E
      deficient mice on the activation of JNK, p38(MAPK), ERK1/2 and NF-kappaB, and the
      expression of RAGE, adhesion molecules and chemokines in the atherosclerotic
      lesions. METHODS: Wild type and apoE-null mice (male, 10-week-old) were treated
      with PNS for 4 weeks. Peripheral blood was collected for assessing the serum
      levels of glucose, lipids and MDA, and activities of SOD and GSH. The sizes of
      atherosclerotic lesions and numbers of macrophages in the branchiocephalic
      arteries, and the reactive oxygen species (ROS) production in the aortic root
      were analyzed. The levels of CD68, Galectin-3, RAGE, JNK, phosphor-JNK,
      p38(MAPK), phosphor-p38(MAPK), ERK1/2, phosphor-ERK1/2, I-kappaB, phosphor-I
      kappaB (Ser32), NF-kappaB, phosphor-NF-kappaB, MCP-1, VCAM-1 and ICAM-1 in the
      descending arteries were identified by Western blot. RESULTS: The atherosclerotic
      lesion sizes, and macrophage numbers, but not the smooth muscle cell amounts and
      the collagen content, were decreased in apoE(-/-) mice treated with PNS. After
      PNS administration for 4 weeks, the apoE(-/-) mice displayed reduced level of
      serum MDA and enhanced activity of SOD and GSH, accompanied by impaired ROS
      generation in the aortic root. Moreover, PNS down-regulated the expression of
      VCAM-1, ICAM-1 and MCP-1, accompanied by reduced expression of RAGE and
      suppressed the activation of NF-kappaB, JNK, p38(MAPK) and ERK1/2. CONCLUSION:
      PNS may inhibit progression of atherosclerotic lesions via their antioxidant/anti
      inflammatory biological properties. PNS suppress the RAGE/MAPK signaling
      pathways, inactivate NF-kappaB, and reduce expression of pro-inflammatory
      factors, such as VCAM-1, ICAM-1 and MCP-1 in atherosclerotic lesions of apoE(-/-)
      mice.

PMID- 22613988
TI  - Influence of constriction, wall tension, smooth muscle activation and cellular
      deformation on rat resistance artery vasodilator reactivity.
AB  - This study investigated how vasoconstriction (tone), wall tension, smooth muscle
      activation, and vascular wall deformation influence resistance artery vasodilator
      reactivity. Resistance arteries, from two different regional circulations
      (splanchnic, uterine) and from pregnant and non-pregnant rats, were cannulated
      and pressurized, or mounted on a wire myograph under isometric conditions prior
      to being exposed to both endothelium-dependent (acetylcholine, ACh) and 
      independent (sodium nitroprusside, SNP) vasodilator agonists. A consistent
      pattern of reduced vasodilator sensitivity was noted as a function of extent of
      preconstriction for both agonists noted in pressurized arteries. A similar
      pattern regarding activation was noted in wire-mounted arteries in response to
      SNP but not ACh. Wall tension proved to be a major determinant of vascular smooth
      muscle vasodilator reactivity and its normalization reversed this pattern, as
      more constricted vessels were more sensitive to ACh relaxation without any change
      in SNP sensitivity, suggesting that endothelial deformation secondary to
      vasoconstriction augments its vasodilator output. To our knowledge, this is the
      first study to dissect out the complex interplay between biophysical forces
      impinging on VSM (pressure, wall tension), the ambient level of tone
      (vasoconstriction, smooth muscle cell activation), and consequences of cellular
      (particularly endothelial) deformation secondary to constriction in determining
      resistance artery vasodilatory reactivity.

PMID- 22613989
TI  - Kruppel-like factor-15 inhibits the proliferation of mesangial cells.
AB  - BACKGROUND/AIMS: The Kruppel-like factor-15 (KLF15), a DNA-binding transcription
      factor, is highly expressed in endothelial and mesangial cells of the kidney.
      However, its effects on mesangial cell proliferation have not previously been
      investigated. In this study, we investigated the effect of KLF15 on mesangial
      cell proliferation. METHODS: We established a classic rat anti-Thy1 mesangial
      proliferative nephritis model. Affymetrix rat U230 2.0 chip was used to detect
      the gene expression profiles at different time point in the model. The different
      expression of KLF15 was shown during mesangial cell proliferation period and
      proliferation declined period of anti-Thy1 nephritis model by microarray
      analysis, Real-time PCR and Western blotting. Then we determined the effects of
      KLF15 and its downstream target, cell cycle regulation factor E2F1 on the
      proliferation of mesangial cells and the expression of the positive-acting cell
      cycle regulatory proteins, cyclinD1 and CDK2, by means of positive and negative
      interference experiments in cultured rat mesangial cells. We detected also
      protein expression of E2F1, cyclinD1 and CDK2 in vivo. RESULTS: By real-time PCR,
      Western blotting, and microarray analysis, KLF15 expression was shown to be lower
      during mesangial cell proliferation period and higher during proliferation
      declined period and under normal conditions. The mesangial cell proliferation was
      reduced and the expression of E2F1, cyclin D1 and CDK2 was downregulated in
      mesangial cells overexpressing KLF15. When KLF15 expression was inhibited by
      siRNA, the expression of E2F1, cyclin D1 and CDK2 and mesangial cell
      proliferation were increased. When E2F1 was inhibited by siRNA, protein level of
      CDK2 and cyclin D1 were lower than control. When siE2F1 was co-transfected with
      siKLF15 into mesangial cells, the increase of cell proliferation induced by
      siKLF15 was eliminated partly by siE2F1. Moreover, E2F1, cyclin D1 and CDK2 were
      higher expression during mesangial cell proliferation period, and were
      downregulated during proliferation declined period in vivo. CONCLUSIONS: These
      results suggest that KLF15 inhibits mesangial cell proliferation, possibly by
      regulating the expression of cell cycle regulation proteins through E2F1. Thus,
      KLF15 may be a useful target for therapeutic intervention in mesangial
      proliferative glomerulonephritis.

PMID- 22613990
TI  - Cholesterol depletion uncouples beta-dystroglycans from discrete sarcolemmal
      domains, reducing the mechanical activity of skeletal muscle.
AB  - BACKGROUND/AIMS: beta-Dystroglycan (beta-DG) is a transmembrane glycoprotein that
      links the intracellular cytoskeleton to the extracellular matrix and is crucial
      for the molecular pathway of lateral force transmission in muscle. We aimed to
      investigate the effect of decreasing sarcolemmal cholesterol on the distribution
      of beta-DG, its interaction with dystrophin and the impact on the contraction
      efficiency of muscle. METHODS: Isolated rat extensor digitorum longus muscles
      were incubated with methyl beta-cyclodextrin (MbetaCD) to deplete cholesterol and
      with MbetaCD-cholesterol to restore cholesterol. Electric stimulation protocols
      were used to determine muscle force and fatigue. Detergent-resistant membranes
      (lipid rafts) were separated from isolated skeletal muscle sarcolemma. The
      distribution and interactions of beta-DG, caveolin-3 and dystrophin were
      determined by an immunoreactivity analysis. RESULTS: Cholesterol depletion in
      muscle results in a weakened force of contraction, which recovers after
      cholesterol restoration. The rate of fatigue is unaffected, but fatigue recovery
      is dependent upon cholesterol restoration. MbetaCD modifies the structures of
      lipid rafts obtained from MbetaCD-treated muscles by, displacing the membrane
      proteins beta-DG and caveolin-3 f from the lipid raft, thus reducing the
      interaction of beta-DG with dystrophin. CONCLUSION: Cholesterol depletion weakens
      the muscle contractile force by disturbing the sarcolemmal distribution of beta
      dystroglycan and its interaction with dystrophin, two key proteins in the
      alignment of lateral force transmission pathway.

PMID- 22613991
TI  - Electrical stimulation induces calcium-dependent up-regulation of neuregulin
      1beta in dystrophic skeletal muscle cell lines.
AB  - Duchenne muscular dystrophy (DMD) is a neuromuscular disease originated by
      reduced or no expression of dystrophin, a cytoskeletal protein that provides
      structural integrity to muscle fibres. A promising pharmacological treatment for
      DMD aims to increase the level of a structural dystrophin homolog called
      utrophin. Neuregulin-1 (NRG-1), a growth factor that potentiates myogenesis,
      induces utrophin expression in skeletal muscle cells. Microarray analysis of
      total gene expression allowed us to determine that neuregulin-1beta (NRG-1beta)
      is one of 150 differentially expressed genes in electrically stimulated (400
      pulses, 1 ms, 45 Hz) dystrophic human skeletal muscle cells (RCDMD). We
      investigated the effect of depolarization, and the involvement of intracellular
      Ca(2+) and PKC isoforms on NRG-1beta expression in dystrophic myotubes.
      Electrical stimulation of RCDMD increased NRG-1beta mRNA and protein levels, and
      mRNA enhancement was abolished by actinomycin D. NRG-1beta transcription was
      inhibited by BAPTA-AM, an intracellular Ca(2+) chelator, and by inhibitors of
      IP(3)-dependent slow Ca(2+) transients, like 2-APB, Ly 294002 and Xestospongin B.
      Ryanodine, a fast Ca(2+) signal inhibitor, had no effect on electrical
      stimulation-induced expression. BIM VI (general inhibitor of PKC isoforms) and Go
      6976 (specific inhibitor of Ca(2+)-dependent PKC isoforms) abolished NRG-1beta
      mRNA induction. Our results suggest that depolarization induced slow Ca(2+)
      signals stimulate NRG-1beta transcription in RCDMD cells, and that Ca(2+)
      dependent PKC isoforms are involved in this process. Based on utrophin's ability
      to partially compensate dystrophin disfunction, knowledge on the mechanism
      involved on NRG-1 up-regulation could be important for new therapeutic strategies
      design.

PMID- 22613992
TI  - Mast cell tryptase induces microglia activation via protease-activated receptor 2
      signaling.
AB  - BACKGROUND: Mast cell tryptase can stimulate peripheral mononuclear cells
      activation to cause widespread inflammation. However, the influence of tryptase
      on microglia, the resident immune cells in the brain, remains uninvestigated.
      Since microglia plays a pivotal role in immune surveillance of CNS, we studied
      the effect of tryptase on microglia activation. METHODS: Induction of microglia
      activation by tryptase was examined with primary cultured microglia. TNF-alpha
      and IL-6 was measured with a commercial ELISA kit. Intracellular ROS was
      determined by dichlorodihydrofluorescein oxidation. Mitochondrial membrane
      potential was assessed with the MitoProbeTM JC-1 assay kit. And MAPK and NF-kappa
      B phosphorylation were evaluated by Western blot. RESULTS: We found that tryptase
      stimulated microglia activation and subsequently produced proinflammatory factors
      TNF-alpha, IL-6 and ROS. Inhibition of PAR-2 activation reduced tryptase-induced
      TNF-alpha, IL-6 and ROS production, and mitochondrial membrane potential loss in
      microglia. Among the three members of MAPK pathway, ERK and p38, but not JNK
      mediated tryptase-induced microglia activation. Inhibition of PAR-2 suppressed
      tryptase-induced ERK and p38 MAPK pathway activation in microglia. Tryptase also
      activated NF-kappa B within 30 min, and ammonium pyrrolidinedithiocarbamate, an
      inhibitor of NF- kappa B, reduced tryptase-induced TNF-alpha and IL-6 release.
      CONCLUSIONS: Our results suggest that tryptase can induce microglia activation
      and pro-inflammatory mediator release via PAR-2-MAPK-NF-kappa B signaling
      pathway, which will contribute to the development of microglia-mediated
      inflammation in brain.

PMID- 22613993
TI  - Ergic2, a brain specific interacting partner of Otoferlin.
AB  - BACKGROUND: Otoferlin, a postulated calcium sensor of 230 kDa, was proposed to
      trigger calcium dependent fusion of vesicles with plasma membrane in the ribbon
      synapses of cochlear IHCs. Otoferlin's interaction with Rab8b and Myo6, proteins
      involved in the intracellular membrane trafficking, extended the previous
      hypothesis assigning Otoferlin an additional role in trans-Golgi trafficking.
      Here, we present another Otoferlin binding partner, Ergic2, a protein with a
      still unknown function but presenting sequence homology to other proteins
      involved in ER/Golgi vesicle trafficking. METHODS: Novel binding partners of
      Otoferlin were searched by yeast two-hybrid screening in a rodent cochlear cDNA
      library (P3-P15). RT-PCR, western blot, immunohistochemistry staining and co
      immunoprecipitation were applied to analyze and confirm an interaction between
      Ergic2 and Otoferlin. RESULTS: The Y-2-H screening, using baits covering parts of
      Otoferlin's C2D domain, identified Ergic2 as an interacting protein for
      Otoferlin. Both are co-expressed (mRNA and protein level) in rodent cochlea and
      brain before- and after-onset of hearing. By RT-PCR Ergic2 was detected in
      cochlear IHCs and OHCs and in brain regions where Otoferlin is known to be
      present. Co-localization studies revealed an overlap of Ergic2 and Otoferlin
      signals in IHCs and neurons of cerebral cortical layer I making Ergic2 the
      promising binding candidate. However, while Ergic2 was co-precipitated by an anti
      Otoferlin antibody in protein lysates from murine brain, this specific protein
      interaction was not detected in cochlea. CONCLUSION: Our new data on Otoferlin's
      interactome suggest that Otoferlin can form different, tissue-specific protein
      complexes.

PMID- 22613994
TI  - The synthesis of a novel chalcone and evaluation for anti-free radical activity
      and antagonizing the learning impairments in Alzheimer's model.
AB  - We synthesized a new chalcone (4,2'-dihydroxy-3methoxy-5-bromine chalcone; C) and
      structurally identified it via infrared spectrometry (IR), (1)H-NMR, mass
      spectrometry (MS) and element analysis (EA). C was confirmed to be highly potent
      in scavenging 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and OH free radicals in
      vitro. Tests of anti-free radical activity in response to oxidative stress in
      mice revealed that C could elevate glutathione peroxidase (GSH-PX) and super
      oxide dismutase (SOD) levels and lower malonaldehyde (MDA) level in a free
      radical-injured scopolamine-induced Alzheimer's model. Further behavioral tests
      with the Morris water maze showed that C could antagonize the learning
      impairments in the Alzheimer's model, which suggests that C has a potential role
      in Alzheimer's disease.

PMID- 22613995
TI  - High-grade sarcomatous overgrowth in solitary fibrous tumors: a clinicopathologic
      study of 10 cases.
AB  - We describe 10 solitary fibrous tumors (SFT) with high-grade malignant
      overgrowth, all of which showed the presence of a synchronous or previous classic
      SFT/malignant SFT (MSFT) component. Seven were "dedifferentiated," with an abrupt
      transition from a classic SFT/MSFT to a high-grade component consisting of a
      nondistinctive high-grade sarcoma in 4 cases and divergent differentiation in 3.
      The nondistinctive high-grade component consisted of epithelioid and/or spindle
      cells often associated with overt pleomorphism or small round cell sarcomas. The
      divergent differentiation featured a rhabdomyosarcoma in 2 cases and an
      osteosarcoma in 1. Three cases (tentatively called "evolved") showed a gradual
      transition from classic SFT/MSFT to a nondistinctive high-grade sarcoma or
      presented features of high-grade sarcoma at the time of metastasis (assessed by
      fine-needle aspiration cytology) without any component suggesting a diagnosis of
      classic SFT/MSFT. The high-grade component showed loss of CD34 expression in half
      of the dedifferentiated SFTs and all of the dedifferentiated SFTs with divergent
      differentiation, whereas Ki-67 was markedly increased in all of the evaluable
      cases and paralleled the tumor grade. In 4 cases, the expression and
      phosphorylation status of key factors that control transcription and protein
      synthesis were also investigated. Both S6 and 4E-BP1 showed low activation in the
      low-grade MSFT and a high level of activation in the high-grade component. Seven
      of the 10 patients died of their disease during follow-up, with a median overall
      survival of 73 months (range, 5 to 288 mo). The median time to distant metastasis
      was 156 months after the initial diagnosis, and median overall survival from the
      first signs of metastasis was 8 months.

PMID- 22613996
TI  - Anaplastic large cell lymphoma associated with breast implants:  a report of 13
      cases.
AB  - We report 13 cases of anaplastic large cell lymphoma (ALCL) associated with
      breast implants. Patient age ranged from 39 to 68 years, and the interval from
      implant to ALCL was 4 to 29 years. All tumors were composed of large, pleomorphic
      cells that were CD30 and ALK1, and all 7 cases assessed had monoclonal T-cell
      receptor gamma-chain rearrangements. Two patient subgroups were identified. Ten
      patients presented with effusion surrounded by fibrous capsule without a grossly
      identifiable tumor mass. Nine patients had stage I and 1 had stage II disease.
      Eight patients underwent implant removal and capsulectomy. Four patients received
      chemotherapy and 4 radiation therapy. All patients were alive without disease at
      last follow-up. A second subgroup of 3 patients had effusion and a distinct mass
      adjacent to the implant. One patient had stage I and 2 stage II disease. One
      patient had a 3-year history of lymphomatoid papulosis, and 1 patient had a 1
      year history of CD30 T-cell lymphoma adjacent to the breast before the diagnosis
      of ALCL associated with breast implant. Two patients received chemotherapy and 1
      radiation therapy. Two patients died 2 and 12 years after diagnosis,
      respectively. We conclude that the clinical behavior of ALCL associated with
      breast implants is heterogeneous. Patients who present with effusion without a
      distinct mass have an indolent disease course, similar to CD30
      lymphoproliferative disorder of skin. In contrast, patients who present with a
      distinct mass may have advanced stage or possibly systemic disease and have a
      poorer prognosis.

PMID- 22613997
TI  - Pathologic features and immunophenotype of estrogen receptor-positive breast
      cancers in BRCA1 mutation carriers.
AB  - Although most breast cancers in BRCA1 mutation carriers are estrogen receptor
      negative (ER-) with a basal-like phenotype, up to one third are ER positive
      (ER+). Little is known about the characteristics of this subgroup. To address
      this, we compared histologic and immunophenotypic features of 60 BRCA1-related
      ER+ breast cancers with those of 85 BRCA1-related ER- cancers and 174 matched ER+
      sporadic cancers. ER+ BRCA1-related cancers were significantly less likely than
      ER- BRCA1-related cancers to be of pure invasive ductal type (P<0.001) and to be
      of histologic grade 3 (P<0.001), and less frequently to have a high mitotic rate
      (P<0.001), pushing (or unknown) margins (P<0.001), a moderate/marked lymphocytic
      infiltrate (P=0.003), or geographic necrosis/fibrotic focus (P<0.001). In
      addition, ER+ BRCA1-related cancers less often expressed CK5/6 (P<0.0001), CK14
      (P<0.0001), and epidermal growth factor receptor (P<0.0001) and more often
      expressed progesterone receptor (P<0.0001). In contrast, when compared with ER+
      sporadic cancers, ER+ BRCA1-related cancers were significantly more often of
      invasive ductal type (P=0.005) and of histologic grade 3 (P=0.006), more
      frequently had a high mitotic rate (P=0.0003), and were more often CK14+
      (P=0.03). On unsupervised cluster analysis, some ER+ BRCA1 cancers clustered more
      closely with sporadic ER+ cancers, whereas others clustered more closely with ER-
      BRCA1-related cancers. Nuclear expression levels of poly(ADP) ribose polymerase 1
      in ER+ BRCA1-related cancers were similar to those in ER- BRCA1-related cancers
      but significantly higher than in ER+ sporadic cancers. We conclude that ER+ BRCA1
      related breast cancers show several morphologic and immunophenotypic differences
      from ER+ sporadic breast cancers as well as some similarities to ER- BRCA1
      related cancers.

PMID- 22613998
TI  - Ovarian serous tumors of low malignant potential with nodal low-grade serous
      carcinoma.
AB  - Serous tumor of low malignant potential (SLMP) and low-grade serous carcinoma
      (LGSC) are part of one biological continuum, whereby SLMP can transform into
      LGSC. It has been suggested that some nodal SLMPs arise from nodal
      endosalpingiosis and evolve independently in lymph nodes (rather than being
      related to the ovarian primary). In this article, we present the
      clinicopathologic features of 5 cases of nodal LGSC presenting in association
      with ovarian SLMP. Clinical information was obtained from the patients' charts.
      Pathologic features of the nodal LGSC, including lymph node location, size of and
      extent of involvement of tumor, architectural pattern, degree of cytologic
      atypia, mitotic index, and presence of psammoma bodies, were recorded. Ovarian
      SLMPs were noted for laterality, size, presence of surface excrescences,
      microinvasion, and micropapillary/cribriform pattern and for presence of
      autoimplants, invasive, and noninvasive implants. The distribution of any lymph
      nodes with nodal endosalpingiosis or SLMPs was also recorded. Patients ranged in
      age from 28 to 68 years (median, 32 y). In 4 cases, the diagnosis of nodal LGSC
      occurred at a different time from that of the ovarian SLMPs, ranging from 7
      months before to 5 months after the ovarian tumor diagnosis. Nodal LGSC was
      detected in supraclavicular (2 cases), cervical, intramammary, and periaortic
      lymph nodes (1 case each). The gross lymph node size ranged from 0.9 to 2.5 cm
      (median, 1.3 cm). The tumors either replaced the entire lymph node or were found
      diffusely involving subcapsular and medullary sinuses or lymph node cortices.
      Tumor cells showed typical cytologic features of LGSC and no mitotic activity. In
      2 cases, however, focal pleomorphic cells and 1 mitosis per 10 HPF were noted.
      Psammoma bodies were identified in all cases. When immunohistochemical analysis
      was performed, all tumors exhibited a profile in keeping with Mullerian origin.
      All ovarian tumors were well sampled and ranged in size from 0.1 to 13 cm
      (median, 2.5 cm). No ovarian SLMP tumors showed the micropapillary/cribriform
      pattern, whereas only focal microinvasion was detected in 3 cases. Four tumors
      had surface excrescences. All cases had noninvasive implants, and a single case
      also had invasive implants. Lymph node dissection was performed in 2 cases,
      revealing extensive endosalpingiosis in pelvic and periaortic lymph nodes and
      SLMP in pelvic lymph nodes. In 1 additional case, a single lymph node was
      sampled, revealing a nodal SLMP. Clinical follow-up ranged from 2 to 14 years
      (median, 9 y). All patients received postoperative chemotherapy. None of the
      patients experienced recurrence in pelvic or abdominal soft tissue. Two patients
      are free of disease. However, 2 patients, one with cervical and another with
      supraclavicular nodal LGSC, had recurrences at these sites and subsequently
      succumbed to metastatic disease. Both of these patients had pelvic and periaortic
      nodal SLMP and extensive nodal endosalpingiosis. Another patient, originally with
      supraclavicular LGSC, developed pelvic and abdominal lymphadenopathy, and is
      currently alive with disease. For the first time, we present a case series of
      patients with ovarian SLMP who, despite any evidence of LGSC in the pelvis or any
      pelvic recurrences, developed extrapelvic/extra-abdominal nodal LGSC. These
      patients also had endosalpingiosis and SLMP in pelvic and periaortic lymph nodes,
      suggesting that SLMP/LGSC tumors in lymph nodes may arise independently of the
      ovarian primary, progress along their own timeline, and undergo metastatic
      spread. Therefore, in patients with ovarian SLMP and extensive pelvic/periaortic
      nodal endosalpingiosis and/or SLMP, examination and follow-up of extrapelvic
      lymph nodes are warranted, even if the ovarian tumor lacks high-risk features of
      recurrence.

PMID- 22613999
TI  - Liver and skin histopathology in adults with acid sphingomyelinase deficiency
      (Niemann-Pick disease type B).
AB  - Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disorder
      characterized by the pathologic accumulation of sphingomyelin (SM) in multiple
      cell types, and occurs most prominently within the liver, spleen, and lungs,
      leading to significant clinical disease. Seventeen ASMD patients underwent a
      liver biopsy during baseline screening for a phase 1 trial of recombinant human
      acid sphingomyelinase (rhASM) in adults with Niemann-Pick disease type B. Eleven
      of the 17 were enrolled in the trial and each received a single dose of rhASM and
      underwent a repeat liver biopsy on day 14. Biopsies were evaluated for fibrosis,
      SM accumulation, and macrophage infiltration by light and electron microscopy.
      When present, fibrosis was periportal and pericellular, predominantly surrounding
      affected Kupffer cells. Two baseline biopsies exhibited frank cirrhosis. SM was
      localized to isolated Kupffer cells in mildly affected biopsies and was present
      in both Kupffer cells and hepatocytes in more severely affected cases.
      Morphometric quantification of SM storage in liver biopsies ranged from 4% to 44%
      of the microscopic field. Skin biopsies were also performed at baseline and day
      14 to compare the SM distribution in a peripheral tissue with that of liver. SM
      storage was present at lower levels in multiple cell types of the skin, including
      dermal fibroblasts, macrophages, vascular endothelial cells, vascular smooth
      muscle cells, and Schwann cells. This phase 1 trial of rhASM in adults with ASMD
      provided a unique opportunity for a prospective assessment of hepatic and skin
      pathology in this rare disease and their potential usage as pharmacodynamic
      biomarkers.

PMID- 22614000
TI  - SMARCB1 deficiency in tumors from the peripheral nervous system: a link between
      schwannomas and rhabdoid tumors?
AB  - BACKGROUND: Inactivation of SMARCB1 tumor-suppressor gene was originally
      described as highly specific for rhabdoid tumors (RTs). Nevertheless, recent
      reports have illustrated that SMARCB1 alterations also characterize other tumors;
      in particular, some familial schwannomatosis and epithelioid malignant peripheral
      nerve sheath tumors, both from peripheral nervous system (PNS) origin, lack BAF47
      expression. To document the putative role of SMARCB1 in PNS, we reviewed PNS
      tumors referred to our institution for a molecular analysis of SMARCB1 because of
      histologic features compatible with RT. METHODS: Clinicopathologic, radiologic,
      and molecular characteristics were detailed for the 12 cases showing loss of
      expression and/or biallelic inactivation of SMARCB1. The status of the NF2 gene,
      likely to synergize with SMARCB1 in PNS tumors, was also analyzed. RESULTS:
      Patients' age ranged from 0 to 45 years (median age, 6.6 y). Neurological
      symptoms were observed in 7/12 cases with radiologic features evoking a
      neuroblastic tumor in 6 cases and a peripheral nerve tumor in 4 cases. The mean
      delay before diagnosis was 3 months. Histologic examination revealed rhabdoid
      features in 11/12 tumors. All tumors showed a complete loss of SMARCB1
      expression. Interestingly, adjacent nervous proliferation resembling
      neurofibromas were observed in 3 cases, suggesting a multistep transformation.
      Three tumors harbored a hemizygous deletion at the NF2 locus, but all NF2
      sequences were normal. CONCLUSIONS: We report the first series of PNS RT. In
      patients with aggressive PNS tumors, RT should be suspected, and anti-SMARCB1
      immunohistochemical analysis should be performed. SMARCB1 inactivation,
      occasionally associated with NF2 deletion, might have oncogenic effects in
      peripheral nerves.

PMID- 22614001
TI  - Will molecular dynamics simulations of proteins ever reach equilibrium?
AB  - We show that conformational entropies calculated for five proteins and protein
      ligand complexes with dihedral-distribution histogramming, the von Mises
      approach, or quasi-harmonic analysis do not converge to any useful precision even
      if molecular dynamics (MD) simulations of 380-500 ns length are employed (the
      uncertainty is 12-89 kJ mol(-1)). To explain this, we suggest a simple protein
      model involving dihedrals with effective barriers forming a uniform distribution
      and show that for such a model, the entropy increases logarithmically with time
      until all significantly populated dihedral states have been sampled, in agreement
      with the simulations (during the simulations, 52-70% of the available dihedral
      phase space has been visited). This is also confirmed by the analysis of the
      trajectories of a 1 ms simulation of bovine pancreatic trypsin inhibitor (31 kJ
      mol(-1) difference in the entropy between the first and second part of the
      simulation). Strictly speaking, this means that it is practically impossible to
      equilibrate MD simulations of proteins. We discuss the implications of such a
      lack of strict equilibration of protein MD simulations and show that ligand
      binding free energies estimated with the MM/GBSA method (molecular mechanics with
      generalised Born and surface-area solvation) vary by 3-15 kJ mol(-1) during a 500
      ns simulation (the higher estimate is caused by rare conformational changes),
      although they involve a questionable but well-converged normal-mode entropy
      estimate, whereas free energies estimated by free-energy perturbation vary by
      less than 0.6 kJ mol(-1) for the same simulation. 

PMID- 22614002
TI  - False positive drugs of abuse immunoassays.

PMID- 22614005
TI  - MicroRNA-7 functions as an anti-metastatic microRNA in gastric cancer by
      targeting insulin-like growth factor-1 receptor.
AB  - Metastasis is a major clinical obstacle in the treatment of gastric cancer (GC)
      and it accounts for the majority of cancer-related mortality. MicroRNAs have
      recently emerged as regulators of metastasis by acting on multiple signaling
      pathways. In this study, we found that miR-7 is significantly downregulated in
      highly metastatic GC cell lines and metastatic tissues. Both gain-of-function and
      loss-of-function experiments showed that increased miR-7 expression significantly
      reduced GC cell migration and invasion, whereas decreased miR-7 expression
      dramatically enhanced cell migration and invasion. In vivo metastasis assays also
      demonstrated that overexpression of miR-7 markedly inhibited GC metastasis.
      Moreover, the insulin-like growth factor-1 receptor (IGF1R) oncogene, which is
      often mutated or amplified in human cancers and functions as an important
      regulator of cell growth and tumor invasion, was identified as a direct target of
      miR-7. Silencing of IGF1R using small interefering RNA (siRNA) recapitulated the
      anti-metastatic function of miR-7, whereas restoring the IGF1R expression
      attenuated the function of miR-7 in GC cells. Furthermore, we found that
      suppression of Snail by miR-7, through targeting IGF1R, increased E-cadherin
      expression and partially reversed the epithelial-mesenchymal transition (EMT).
      Finally, analyses of miR-7 and IGF1R levels in human primary GC with matched
      lymph node metastasis tissue arrays revealed that miR-7 is inversely correlated
      with IGF1R expression. The present study provides insight into the specific
      biological behavior of miR-7 in EMT and tumor metastasis. Targeting this novel
      miR-7/IGF1R/Snail axis would be helpful as a therapeutic approach to block GC
      metastasis.

PMID- 22614004
TI  - Mitochondrial activation by inhibition of PDKII suppresses HIF1a signaling and
      angiogenesis in cancer.
AB  - Most solid tumors are characterized by a metabolic shift from glucose oxidation
      to glycolysis, in part due to actively suppressed mitochondrial function, a state
      that favors resistance to apoptosis. Suppressed mitochondrial function may also
      contribute to the activation of hypoxia-inducible factor 1alpha (HIF1alpha) and
      angiogenesis. We have previously shown that the inhibitor of pyruvate
      dehydrogenase kinase (PDK) dichloroacetate (DCA) activates glucose oxidation and
      induces apoptosis in cancer cells in vitro and in vivo. We hypothesized that DCA
      will also reverse the 'pseudohypoxic' mitochondrial signals that lead to
      HIF1alpha activation in cancer, even in the absence of hypoxia and inhibit cancer
      angiogenesis. We show that inhibition of PDKII inhibits HIF1alpha in cancer cells
      using several techniques, including HIF1alpha luciferase reporter assays. Using
      pharmacologic and molecular approaches that suppress the prolyl-hydroxylase (PHD)
      mediated inhibition of HIF1alpha, we show that DCA inhibits HIF1alpha by both a
      PHD-dependent mechanism (that involves a DCA-induced increase in the production
      of mitochondria-derived alpha-ketoglutarate) and a PHD-independent mechanism,
      involving activation of p53 via mitochondrial-derived H(2)O(2), as well as
      activation of GSK3beta. Effective inhibition of HIF1alpha is shown by a decrease
      in the expression of several HIF1alpha regulated gene products as well as
      inhibition of angiogenesis in vitro in matrigel assays. More importantly, in rat
      xenotransplant models of non-small cell lung cancer and breast cancer, we show
      effective inhibition of angiogenesis and tumor perfusion in vivo, assessed by
      contrast-enhanced ultrasonography, nuclear imaging techniques and histology. This
      work suggests that mitochondria-targeting metabolic modulators that increase
      pyruvate dehydrogenase activity, in addition to the recently described pro
      apoptotic and anti-proliferative effects, suppress angiogenesis as well,
      normalizing the pseudo-hypoxic signals that lead to normoxic HIF1alpha activation
      in solid tumors.

PMID- 22614003
TI  - Chromosomal instability and aneuploidy in cancer: from yeast to man.
AB  - Aneuploidy is frequently associated with disease and developmental abnormalities.
      It is also a key characteristic of cancer. Several model systems have been
      developed to study the role of chromosomal instability and aneuploidy in
      tumorigenesis. The results are surprisingly complex, with the conditions
      sometimes promoting and sometimes inhibiting tumour formation. Here, we review
      the effects of aneuploidy and chromosomal instability in cells and model systems
      of cancer, propose a model that could explain these complex findings and discuss
      how the aneuploid condition could be exploited in cancer therapy.

PMID- 22614006
TI  - KIBRA exhibits MST-independent functional regulation of the Hippo signaling
      pathway in mammals.
AB  - The Salvador/Warts/Hippo (Hippo) signaling pathway defines a novel signaling
      cascade regulating cell contact inhibition, organ size control, cell growth,
      proliferation, apoptosis and cancer development in mammals. The upstream
      regulation of this pathway has been less well defined than the core kinase
      cassette. KIBRA has been shown to function as an upstream member of the Hippo
      pathway by influencing the phosphorylation of LATS and YAP, but functional
      consequences of these biochemical changes have not been previously addressed. We
      show that in MCF10A cells, loss of KIBRA expression displays epithelial-to
      mesenchymal transition (EMT) features, which are concomitant with decreased LATS
      and YAP phosphorylation, but not MST1/2. In addition, ectopic KIBRA expression
      antagonizes YAP via the serine 127 phosphorylation site and we show that KIBRA,
      Willin and Merlin differentially regulate genes controlled by YAP. Finally,
      reduced KIBRA expression in primary breast cancer specimens correlates with the
      recently described claudin-low subtype, an aggressive sub-group with EMT features
      and a poor prognosis.

PMID- 22614007
TI  - BTG2 loss and miR-21 upregulation contribute to prostate cell transformation by
      inducing luminal markers expression and epithelial-mesenchymal transition.
AB  - Prostate cancer is one of the leading causes of cancer-related death in men.
      Despite significant advances in prostate cancer diagnosis and management, the
      molecular events involved in the transformation of normal prostate cells into
      cancer cells have not been fully understood. It is generally accepted that
      prostate cancer derives from the basal compartment while expressing luminal
      markers. We investigated whether downregulation of the basal protein B-cell
      translocation gene 2 (BTG2) is implicated in prostate cancer transformation and
      progression. Here we show that BTG2 loss can shift normal prostate basal cells
      towards luminal markers expression, a phenotype also accompanied by the
      appearance of epithelial-mesenchymal transition (EMT) traits. We also show that
      the overexpression of microRNA (miR)-21 suppresses BTG2 levels and promotes the
      acquisition of luminal markers and EMT in prostate cells. Furthermore, by using
      an innovative lentiviral vector able to compete with endogenous mRNA through the
      overexpression of the 3'-untranslated region of BTG2, we demonstrate that in
      prostate tumor cells, the levels of luminal and EMT markers can be reduced by
      derepression of BTG2 from microRNA-mediated control. Finally, we show that the
      loss of BTG2 expression confers to non-tumorigenic prostate cells ability to grow
      in an orthotopic murine model, thus demonstrating the central role of BTG2
      downregulaton in prostate cancer biology.

PMID- 22614008
TI  - Nicotine/cigarette smoke promotes metastasis of pancreatic cancer through
      alpha7nAChR-mediated MUC4 upregulation.
AB  - Despite evidence that long-term smoking is the leading risk factor for pancreatic
      malignancies, the underlying mechanism(s) for cigarette-smoke (CS)-induced
      pancreatic cancer (PC) pathogenesis has not been well established. Our previous
      studies revealed an aberrant expression of the MUC4 mucin in PC as compared with
      the normal pancreas, and its association with cancer progression and metastasis.
      Interestingly, here we explore a potential link between MUC4 expression and
      smoking-mediated PC pathogenesis and report that both cigarette smoke extract and
      nicotine, which is the major component of CS, significantly upregulates MUC4 in
      PC cells. This nicotine-mediated MUC4 overexpression was via the alpha7 subunit
      of nicotinic acetylcholine receptor (nAChR) stimulation and subsequent activation
      of the JAK2/STAT3 downstream signaling cascade in cooperation with the MEK/ERK1/2
      pathway; this effect was blocked by the alpha7nAChR antagonists, alpha
      bungarotoxin and mecamylamine, and by specific siRNA-mediated STAT3 inhibition.
      In addition, we demonstrated that nicotine-mediated MUC4 upregulation promotes
      the PC cell migration through the activation of the downstream effectors, such as
      HER2, c-Src and FAK; this effect was attenuated by shRNA-mediated MUC4
      abrogation, further implying that these nicotine-mediated pathological effects on
      PC cells are MUC4 dependent. Furthermore, the in vivo studies showed a marked
      increase in the mean pancreatic tumor weight (low dose (100 mg/m(3) total
      suspended particulate (TSP)), P=0.014; high dose (247 mg/m(3) TSP), P=0.02) and
      significant tumor metastasis to various distant organs in the CS-exposed mice,
      orthotopically implanted with luciferase-transfected PC cells, as compared with
      the sham controls. Moreover, the CS-exposed mice had elevated levels of serum
      cotinine (low dose, 155.88+/-35.96 ng/ml; high dose, 216.25+/-29.95 ng/ml) and
      increased MUC4, alpha7nAChR and pSTAT3 expression in the pancreatic tumor
      tissues. Altogether, our findings revealed for the first time that CS upregulates
      the MUC4 mucin in PC via the alpha7nAChR/JAK2/STAT3 downstream signaling cascade,
      thereby promoting metastasis of PC.

PMID- 22614009
TI  - Retinoblastoma protein-interacting zinc-finger gene 1 (RIZ1) dysregulation in
      human malignant meningiomas.
AB  - Retinoblastoma protein-interacting zinc-finger gene 1 (RIZ1) expression is often
      silenced in many types of human tumors. However, the relationship between RIZ1
      expression and malignant meningiomas remains unclear. Here we have found for the
      first time that the expression of RIZ1 genes are associated with meningiomas
      progression through extensive analyses of Affymetrix GeneChip microarray data.
      Further validation methods for gene expression included quantitative PCR (qPCR),
      western blot and immunohistochemistry analysis, and these methods confirmed that
      RIZ1 is significantly downregulated in malignant meningioma tissues, as compared
      with benign meningiomas. In addition, malignant meningioma cells were stably
      transfected with ectogenic RIZ1 using Lentivirus-mediated transfection, and the
      transfections were followed by an in vitro 5-bromo-2-deoxyuridin incorporation
      assay, colony formation assay, cell cycle analysis, invasive analysis, apoptotic
      assay and western blot analysis. Our results demonstrate that the forced
      expression of RIZ1 in a malignant meningioma cell line inhibited cellular
      proliferation and arrested the cells in the G2/M phase of the cell cycle. We also
      confirmed that overexpression of RIZ1 may induce apoptosis of malignant
      meningioma cells. Furthermore, RIZ1 overexpression in malignant meningioma cells
      was associated with the downregulation of c-myc expression. These results from
      our study indicate that RIZ1 expression is significantly downregulated as the
      formation of meningiomas progressed, and suggest that RIZ1 may represent a
      promising candidate tumor suppressor gene that contributes to malignant
      meningiomas.

PMID- 22614010
TI  - Genome-wide mechanisms of Smad binding.
AB  - A dual role of transforming growth factor beta (TGF-beta), to both suppress and
      promote tumor progression and metastasis, has been well established, but its
      molecular basis has remained elusive. In this review, we focus on Smad proteins,
      which are central mediators of the signal transduction of TGF-beta family
      members. We describe current knowledge of cell-type-specific binding patterns of
      Smad proteins and mechanisms of transcriptional regulation, obtained from recent
      studies on genome-wide binding sites of Smad molecules. We also discuss potential
      application of the genome-wide analyses for cancer research, which will allow
      clarification of the complex mechanisms occurring during cancer progression, and
      the identification of potential biomarkers for future cancer diagnosis, prognosis
      and therapy.

PMID- 22614011
TI  - Vasohibin 2 is transcriptionally activated and promotes angiogenesis in
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) typically relies on angiogenesis for its malignant
      behavior, including growth and metastasis. Vasohibin 2 (VASH2) was previously
      identified as an angiogenic factor, but its role in tumorigenesis is unknown.
      Using quantitative PCR and western blot analyses, we found that VASH2 is
      overexpressed in HCC cells and tissues. Using chromatin immunoprecipitation, we
      detected histone modifications at the putative VASH2 promoter, with increased
      H3K4 trimethylation and H3 acetylation and decreased H3K27 trimethylation,
      suggesting that epigenetic mechanisms are responsible for the deregulated VASH2
      transcription in HCC. Knockdown of VASH2 via siRNA inhibited the proliferation of
      the hepatoma cell lines by delaying cell cycle progression and increasing
      apoptosis. Importantly, we found VASH2 secreted in the culture supernatant, and
      co-expression of its secretory chaperone small vasohibin-binding protein (SVBP)
      further enhanced VASH2 secretion. The supernatant from HepG2 cells expressing
      VASH2 enhanced the proliferation, migration and tube formation of human umbilical
      vein endothelial cells, and knockdown of VASH2 significantly inhibited these
      effects. In an in vivo study using a nude mouse model, we found that exogenous
      VASH2 significantly contributed to tumor growth, microvessel density and
      hemoglobin concentration in the tumors. Further analyses showed that the VASH2
      mediated increase in the transcription of fibroblast growth factor-2, vascular
      endothelial growth factor and vasohibin 1 may be the mechanism underlying these
      effects. Taken together, these data indicate that VASH2 is abnormally expressed
      in HCC cells as a result of histone modifications and that VASH2 contributes to
      the angiogenesis in HCC via an SVBP-mediated paracrine mechanism. These results
      indicate a novel and important role for VASH2 in HCC angiogenesis and malignant
      transformation.

PMID- 22614012
TI  - Lipocalin 2 performs contrasting, location-dependent roles in APCmin tumor
      initiation and progression.
AB  - Evidence that lipocalin 2 (LCN2) is oncogenic has grown in recent years and comes
      from both animal models and expression analysis from a variety of human cancers.
      In the intestine, LCN2 is overexpressed in colitis patients and its
      overexpression is a negative prognostic indicator in colorectal cancer.
      Functionally, LCN2 has a number of different activities that may contribute to
      its oncogenic potential, including increasing matrix metalloproteinase activity,
      control of iron availability and stimulating inflammation. In this report, we
      examined APCmin intestinal tumorigenesis in an LCN2-deficient background. We
      found that the loss of LCN2 increased tumor multiplicity specifically in the
      duodenum, suggesting a potential tumor-suppressive activity. Concurrently,
      however, LCN2 increased the average small intestinal tumor size particularly in
      the distal small intestine. We found that this increase was correlated to tumor
      iron(II) content, suggesting that an iron-scavenging role is important for LCN2
      oncogenic activity in the intestine.

PMID- 22614013
TI  - Functional screen analysis reveals miR-26b and miR-128 as central regulators of
      pituitary somatomammotrophic tumor growth through activation of the PTEN-AKT
      pathway.
AB  - MicroRNAs (miRNAs) have been involved in the pathogenesis of different types of
      cancer; however, their function in pituitary tumorigenesis remains poorly
      understood. Cyclic-AMP-dependent protein kinase-defective pituitaries
      occasionally form aggressive growth-hormone (GH)-producing pituitary tumors in
      the background of hyperplasia caused by haploinsufficiency of the protein
      kinase's main regulatory subunit, PRKAR1A. The molecular basis for this
      development remains unknown. We have identified a 17-miRNA signature of pituitary
      tumors formed in the background of hyperplasia (caused in half of the cases by
      PRKAR1A-mutations). We selected two miRNAs on the basis of their functional
      screen analysis: inhibition of miR-26b expression and upregulation of miR-128
      suppressed the colony formation ability and invasiveness of pituitary tumor
      cells. Furthermore, we identified that miR-26b and miR-128 affected pituitary
      tumor cell behavior through regulation of their direct targets, PTEN and BMI1,
      respectively. In addition, we found that miR-128 through BMI1 direct binding on
      the PTEN promoter affected PTEN expression levels and AKT activity in the
      pituitary tumor cells. Our in vivo data revealed that inhibition of miR-26b and
      overexpression of miR-128 could suppress pituitary GH3 tumor growth in
      xenografts. Taken together, we have identified a miRNA signature for GH-producing
      pituitary tumors and found that miR-26b and miR-128 regulate the activity of the
      PTEN-AKT pathway in these tumors. This is the first suggestion of the possible
      involvement of miRNAs regulating the PTEN-AKT pathway in GH-producing pituitary
      tumor formation in the context of hyperplasia or due to germline PRKAR1A defects.
      MiR-26b suppression and miR-128 upregulation could have therapeutic potential in
      GH-producing pituitary tumor patients.

PMID- 22614014
TI  - Macrophage cathepsin K promotes prostate tumor progression in bone.
AB  - Bone marrow macrophages (BMMs) share common progenitors with osteoclasts and are
      critical components of bone-tumor microenvironment; however, their function in
      prostate tumor growth in the skeleton has not been explored. BMMs are the major
      source of inflammatory factors and proteases, including cysteine protease
      cathepsin K (CTSK). In this study, utilizing mice deficient in CTSK, we
      demonstrate the critical involvement of this potent collagenase in tumor
      progression in bone. We present the evidence that tumor growth and progression in
      the bone are impaired in the absence of CTSK. Most importantly, we show for the
      first time that BMM-supplied CTSK may be involved in CCL2- and COX-2-driven
      pathways that contribute to tumor progression in bone. Together, our data unravel
      novel roles for CTSK in macrophage-regulated processes, and provide evidence for
      close interplay between inflammatory, osteolytic and tumor cell-driven events in
      the bone-tumor microenvironment.

PMID- 22614015
TI  - The tumour suppressor HACE1 controls cell migration by regulating Rac1
      degradation.
AB  - The small GTPase Rac1 is a key regulator of cell motility. Multiple mechanisms
      regulate Rac1 activity including its ubiquitylation and subsequent degradation.
      Here, we identify the tumour suppressor HACE1 (HECT domain and Ankyrin repeat
      Containing E3 ubiquitin-protein ligase 1) as an E3 ubiquitin ligase responsible
      for Rac1 degradation following activation by a migration stimulus. We show that
      HACE1 and Rac1 interaction is enhanced by hepatocyte growth factor (HGF)
      signalling, a Rac activator and potent stimulus of cell migration. Furthermore,
      HACE1 catalyses the poly-ubiquitylation of Rac1 at lysine 147 following its
      activation by HGF, resulting in its proteasomal degradation. This negative
      feedback mechanism likely restricts cell motility. Consistent with this, HACE1
      depletion is accompanied by increased total Rac1 levels and accumulation of Rac1
      in membrane ruffles. Moreover, HACE1-depletion enhances cell migration
      independently of growth factor stimulation, which may have significance for
      malignant conversion. A non-ubiquitylatable Rac1 rescues the migration defect of
      Rac1-null cells to a greater extent than wild-type Rac1. These findings identify
      HACE1 as an antagonist of cell migration through its ability to degrade active
      Rac1.

PMID- 22614016
TI  - Therapy-resistant tumor microvascular endothelial cells contribute to treatment
      failure in glioblastoma multiforme.
AB  - Glioblastoma multiforme (GBM) is a devastating disease with high mortality and
      poor prognosis. Cancer stem cells (CSCs) have recently been defined as a fraction
      of tumor cells highly resistant to therapy and subsequently considered to be
      responsible for tumor recurrence. These cells have been characterized in GBM and
      suggested to reside in and be supported by the tumor microvascular niche. Here we
      evaluated the response of tumor microvascular endothelial cells (tMVECs) to radio
      and chemotherapy, and analyzed how this affects their interaction with CSCs. Our
      data demonstrate that tMVECs exhibit extreme resistance to both therapies, with
      the main response to irradiation being senescence. Importantly, senescent tMVECs
      can be detected in human GBM samples as well as in mice upon irradiation. Even
      though permanently arrested, they are still viable and able to support CSC growth
      with the same efficacy as non-senescent tMVECs. Intriguingly, GBM CSCs themselves
      are capable of differentiating into cells with similar features as tMVECs that
      subsequently undergo senescence when exposed to radiation. This indicates that
      endothelial-like cells are therapy resistant and, more importantly, support
      expansion of GBM cells.

PMID- 22614017
TI  - HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in
      pancreatic cancer.
AB  - HOTAIR is a long intervening non-coding RNA (lincRNA) that associates with the
      Polycomb Repressive Complex 2 (PRC2) and overexpression is correlated with poor
      survival for breast, colon and liver cancer patients. In this study, we show that
      HOTAIR expression is increased in pancreatic tumors compared with non-tumor
      tissue and is associated with more aggressive tumors. Knockdown of HOTAIR
      (siHOTAIR) by RNA interference shows that HOTAIR has an important role in
      pancreatic cancer cell invasion, as reported in other cancer cell lines. In
      contrast, HOTAIR knockdown in Panc1 and L3.6pL pancreatic cancer cells that
      overexpress this lincRNA decreased cell proliferation, altered cell cycle
      progression and induced apoptosis, demonstrating an expanded function of HOTAIR
      in pancreatic cancer cells compared with other cancer cell lines. Results of gene
      array studies showed that there was minimal overlap between HOTAIR-regulated
      genes in pancreatic cells and breast cancer cells, and HOTAIR uniquely suppressed
      several interferon-related genes and gene sets related to cell cycle progression
      in pancreatic cancer cells and tumors. Analysis of selected genes suppressed by
      HOTAIR in Panc1 and L3.6pL cells showed by knockdown of EZH2 and chromatin
      immunoprecipitation assays that HOTAIR-mediated gene repression was both PRC2
      dependent and -independent. HOTAIR knockdown in L3.6pL cells inhibited tumor
      growth in mouse xenograft model, further demonstrating the pro-oncogenic function
      of HOTAIR in pancreatic cancer.

PMID- 22614018
TI  - Promotion of DNA repair by nuclear IKKbeta phosphorylation of ATM in response to
      genotoxic stimuli.
AB  - Ataxia-telangiectasia mutated (ATM) is one of the key molecules involved in the
      cellular response to DNA damage. A portion of activated ATM is exported from the
      nucleus into the cytoplasm, where it activates the I kappa B kinase/nuclear
      factor kappa B (IKK/NF-kappaB) signaling pathway. It has been thought that
      activated IKKbeta, which is a critical kinase for NF-kappaB activation, generally
      resides in the cytoplasm and phosphorylates cytoplasmic downstream molecules,
      such as IkappaBalpha. Here, we identified a new role for IKKbeta during the
      response to DNA damage. ATM phosphorylation in response to alkylating agents
      consisted of two phases: the early phase (up to 3 h) and late phase (after 6 h).
      A portion of the activated IKKbeta generated during the DNA damage response was
      found to translocate into the nucleus and directly phosphorylate ATM in the late
      phase. Furthermore, the phosphorylation of ATM by nuclear IKKbeta was suggested
      to promote DNA repair. In parallel, activated IKKbeta induced classical NF-kappaB
      activation and was involved in anti-apoptosis. Our findings define the function
      of IKKbeta during the response to DNA damage, which promotes cell survival and
      DNA repair, and maintains cellular homeostasis.

PMID- 22614019
TI  - The Grainyhead transcription factor Grhl3/Get1 suppresses miR-21 expression and
      tumorigenesis in skin: modulation of the miR-21 target MSH2 by RNA-binding
      protein DND1.
AB  - Epidermal differentiation and stratification, crucial for barrier formation, are
      regulated by a complex interplay of transcription factors, including the
      evolutionarily conserved Grainyhead-like 3 (Grhl3/Get1); Grhl3-deleted mice
      exhibit impaired epidermal differentiation and decreased expression of multiple
      differentiation genes. To test whether Grhl3 regulates epidermal genes indirectly
      by controlling the expression of specific microRNAs (miRs), we performed miR
      profiling and identified 11 miRs that are differentially regulated in Grhl3(-/-)
      skin, one of which is miR-21, previously shown to be upregulated in diseased
      skin, including in psoriasis and squamous cell skin cancer. We found that miR-21
      is normally expressed in the post-mitotic suprabasal layers of the epidermis,
      overlapping with Grhl3. The miR-21 promoter is bound and repressed by Grhl3
      indicating that these two factors are involved in a regulatory loop maintaining
      homeostasis in the epidermis. Although miR-21 overexpression in normal
      keratinocytes had mild effects on the expression of several known miR-21 targets,
      an enhanced downregulation of the miR-21 tumor-related targets, including MSH2,
      was observed in Ras-transformed keratinocytes. The increased sensitivity of
      transformed keratinocytes to miR-21's effects occurs in part through
      downregulation of the RNA-binding protein DND1 during the transformation process.
      Additionally, we observed increased tumorigenesis in mice subcutaneously injected
      with transformed keratinocytes lacking Grhl3. These findings indicate that
      decreased Grhl3 expression contributes to tumor progression and upregulation of
      the oncomir miR-21 in squamous cell carcinoma of the skin.

PMID- 22614022
TI  - Cross-talk between phosphorylation and SUMOylation regulates transforming
      activities of an adenoviral oncoprotein.
AB  - Since the discovery of post-translational modification (PTM) by the small
      ubiquitin-related modifiers (SUMOs), a multitude of proteins have been described
      to be reversibly modified, resulting in the alteration of several cellular
      pathways. Interestingly, various pathogens gain access to this modification
      system, although the molecular mechanisms and functional consequences are barely
      understood. We show here that the adenoviral oncoprotein E1B-55K is a substrate
      of the SUMO conjugation system, which is directly linked to its C-terminal
      phosphorylation. This regulative connection is indispensable for modulation of
      the tumor suppressor p53/chromatin-remodeling factor Daxx by E1B-55K and,
      consequently, its oncogenic potential in primary mammalian cells. In virus
      infection, E1B-55K PTMs are necessary for localization to viral
      transcription/replication sites. Furthermore, we identify the E2 enzyme Ubc9 as
      an interaction partner of E1B-55K, providing a possible molecular explanation for
      SUMO-dependent modulation of cellular target proteins. In conclusion, these
      results for the first time provide evidence how E1B-55K PTMs are regulated and
      subsequently facilitate exploitation of the host cell SUMOylation machinery.

PMID- 22614020
TI  - PARP1 and DNA-PKcs synergize to suppress p53 mutation and telomere fusions during
      T-lineage lymphomagenesis.
AB  - Poly(ADP-ribose) polymerase 1 (PARP1) interacts genetically with the DNA
      dependent protein kinase catalytic subunit (DNA-PKcs) to suppress early-onset T
      lineage lymphomas in the mouse, but the underlying mechanisms have remained
      unknown. To address this question, we analyzed a series of lymphomas arising in
      PARP1(-/-)/DNA-PKcs(-/-) (P1(-/-)/D(-/-)) mice. We found that, despite defective
      V(D)J recombination, P1(-/-)/D(-/-) lymphomas lacked clonal reciprocal
      translocations involving antigen-receptor loci. Instead, tumor cells were
      characterized by aneuploidy driven by two main mechanisms: p53 inactivation and
      abnormal chromosome disjunction due to telomere fusions (TFs). Aberrant
      accumulation of p53 was observed in 13/19 (68.4%) lymphomas. Sequence analysis
      revealed five p53 mutations: three missense point mutations (one transition in
      exon 8 and two transversions in exons 5 and 8, respectively), one in-frame 5-11
      microindel in exon 7 and a 410-bp deletion encompassing exons 5-8, resulting in a
      truncated protein. Analysis of tumor metaphases using sequential telomere
      fluorescent in-situ hybridization and spectral karyotyping revealed that nine out
      of nine lymphomas contained TFs. Mutant but not wild-type p53 status was
      associated with frequent clonal and nonclonal TFs, suggesting that p53 normally
      limits the extent of telomere dysfunction during transformation. Chromosomes
      involved in TFs were more likely to be aneuploid than chromosomes not involved in
      TFs in the same metaphases, regardless of the p53 status, indicating that TFs
      promote aneuploidy via a mechanism that is distinct from p53 loss. Finally,
      analysis of radiation responses in P1(-/-)/D(-/-), and control primary cells and
      tissues indicates that loss of PARP1 increases in vivo radiosensitivity and
      genomic instability in DNA-PKcs-deficient mice without impairing p53
      stabilization and effector functions, suggesting a more severe defect in double
      strand break (DSB) repair in double mutants. Together, our findings uncover
      defective DSB repair leading to tumor suppressor inactivation and abnormal
      segregation of fused chromosomes as two novel mechanisms promoting tumorigenesis
      in thymocytes lacking PARP1 and DNA-PKcs.

PMID- 22614023
TI  - Culture-proven neonatal sepsis in Japanese neonatal care units in 2006-2008.
AB  - BACKGROUND: Recent Japanese epidemiology of neonatal sepsis and its predominant
      pathogens has not been reported. It is also unknown whether there are center
      differences in the incidence of neonatal sepsis, including early-onset sepsis
      (EOS) and late-onset sepsis (LOS) in Japan. OBJECTIVES: To investigate the
      morbidity and characteristics of neonatal sepsis in recent years and the
      differences in the incidence of sepsis among Japanese neonatal care units.
      METHODS: We retrospectively collected the data of newborn infants with culture
      proven sepsis that occurred in five Japanese centers of perinatal care from 2006
      to 2008. The incidence of sepsis was calculated, including EOS and LOS, and
      compared among centers. RESULTS: Morbidity from sepsis occurred in 51/6,894
      (0.74%) infants. The incidence of EOS and LOS was 0.13 and 0.61%, respectively.
      The incidence of total sepsis and LOS in infants <1,000 g of birth weight was
      significantly higher than that in infants who weighed >1,000 g at birth, whereas
      there were no significant differences in the incidence of EOS between the
      different birth weights. Methicillin-resistant Staphylococcus aureus was the most
      common pathogen involved in morbidity and mortality of neonatal sepsis.
      Significant center differences were observed in the incidence of LOS, but not
      EOS. CONCLUSIONS: The majority of culture-proven neonatal sepsis is LOS, which
      differs among centers, especially in infants who weigh <1,000 g at birth in
      Japan. We consider that it is important to control nosocomial infection in
      newborn care units to further reduce the morbidity of neonatal sepsis in Japan.

PMID- 22614021
TI  - Basic anatomy and tumor biology of the RPS6KA6 gene that encodes the p90
      ribosomal S6 kinase-4.
AB  - The RPS6KA6 gene encodes the p90 ribosomal S6 kinase-4 (RSK4) that is still
      largely uncharacterized. In this study we identified a new RSK4 transcription
      initiation site and several alternative splice sites with a 5'-RACE approach. The
      resulting mRNA variants encompass four possible first start codons. The first 15
      nucleotides (nt) of exon 22 in mouse and the penultimate exon in both human (exon
      21) and mouse (exon 24) RSK4 underwent alternative splicing, although the
      penultimate exon deleted variant appeared mainly in cell clines, but not in most
      normal tissues. Demethylation agent 5-azacytidine inhibited the deletion of the
      penultimate exon, whereas two indolocarbazole-derived inhibitors of cyclin
      dependent kinase 4 or 6 induced deletion of the first 39 nt from exon 21 of human
      RSK4. In all human cancer cell lines studied, the 90-kDa wild-type RSK4 was
      sparse but, surprisingly, several isoforms at or smaller than 72 kDa were
      expressed as detected by seven different antibodies. On immunoblots, each of
      these smaller isoforms often appeared as a duplet or triplet and the levels of
      these isoforms varied greatly among different cell lines and culture conditions.
      Cyclin D1 inhibited RSK4 expression and serum starvation enhanced the inhibition,
      whereas c-Myc and RSK4 inhibited cyclin D1. The effects of RSK4 on cell growth,
      cell death and chemoresponse depended on the mRNA variant or the protein isoform
      expressed, on the specificity of the cell lines, as well as on the anchorage
      dependent or -independent growth conditions and the in vivo situation. Moreover,
      we also observed that even a given cDNA might be expressed to multiple proteins;
      therefore, when using a cDNA, one needs to exclude this possibility before
      attribution of the biological results from the cDNA to the anticipated protein.
      Collectively, our results suggest that whether RSK4 is oncogenic or tumor
      suppressive depends on many factors.

PMID- 22614024
TI  - Genotoxic biomonitoring of tobacco farmers: Biomarkers of exposure, of early
      biological effects and of susceptibility.
AB  - Tobacco farming presents several hazards to those who cultivate and harvest the
      plant. The genotoxic and mutagenic effects in tobacco farmers were investigated.
      In order to verify the relationship between genetic susceptibility and biomarkers
      GSTT1, GSTM1, GSTP1, CYP2A6, PON, OGG1, RAD51, XRCC1, and XRCC4 genes
      polymorphism were evaluated. Oxidative stress markers and trace elements content
      were determined. Peripheral blood cells samples were collected from 111
      agricultural workers during pesticides application and leaf harvest, and 56 non
      exposed subjects. Results show that farmers are exposed to mixture of substances
      with genotoxic and cytotoxic potential. Only GSTM1 null and CYP2A6*9 showed
      significant associations with cytokinesis-blocked micronuclei assay results. In
      pesticide application an increase in trace elements content was observed. The
      results indicated that exposure to pesticides and nicotine can influence
      antioxidant enzymes activity. Our study drives the attention once more to the
      need for occupational training on safe work environment for farm workers.

PMID- 22614025
TI  - Experimental investigation of influence of acid rain on leaching and hydraulic
      characteristics of cement-based solidified/stabilized lead contaminated clay.
AB  - Remediation of contaminated lands in China urban areas is of great concern.
      Degradation of construction facilities caused by acid rain is a serious
      environmental pollution issue in China. This paper presents an investigation of
      the effects of acid rain on leaching and hydraulic properties of cement-based
      solidified/stabilized lead contaminated soil. Laboratory tests including
      infiltration test and soaking test are conducted. It is found that the soil
      hydraulic conductivity decreases with increase in the pore volume of flow of
      permeant liquids (acid rain and distilled water). The decreasing rate in the case
      of the acid rain is lower than that in the case of the distilled water. The
      soaking test results show that pH and the presence of sulfate ions of acid rain
      have considerable influence on the leached concentrations and leaching rate of
      calcium.

PMID- 22614026
TI  - Uptake, accumulation, and biotransformation of metal oxide nanoparticles by a
      marine suspension-feeder.
AB  - A growing body of evidence indicates that some engineered nanoparticles (ENPs)
      are toxic to organisms that perform important ecosystem services in terrestrial
      and aquatic ecosystems. However, toxicity can be influenced by the
      biotransformation of contaminants, including ENPs, as it may alter the fate and
      transport of these substances. In turn, fate and transport can influence their
      bioavailability. To understand how biotransformation influences the fate and
      transport of ENPs in marine ecosystems, we exposed suspension-feeding mussels,
      Mytilus galloprovincialis, to two common nano-metal oxides, CeO(2) and ZnO, over
      a range of concentrations from 1mg L(-1) to 10mg L(-1), in a laboratory
      experiment. Mussels exposed to 10mg L(-1) accumulated 62MUg g(-1) of Ce and
      880MUg g(-1) of Zn on a dry tissue basis but rejected 21,000MUg g(-1) for Ce and
      63,000MUg g(-1) for Zn in pseudofeces. Scanning electron microscope evidence
      indicates CeO(2) remained as ENPs but ZnO did not after being rejected by the
      mussels. Mussels filtered most of the CeO(2) from the aqueous media, while a
      significant fraction of Zn remained in solution. Differences in ENP solubility
      affect ENP uptake, excretion, and accumulation in mussels. Our study highlights
      the potential role of marine suspension feeders in biotransformation of ENPs.

PMID- 22614027
TI  - Organo/LDH nanocomposite as an adsorbent of polycyclic aromatic hydrocarbons in
      water and soil-water systems.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are considered as priority pollutants
      because of their high risk to human health. In this paper, we addressed the issue
      of using hydrotalcite-based nanocomposites as adsorbents of six low molecular
      weight PAHs (acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene and
      pyrene) to reduce their negative effects on the environment. A nanocomposite (HT
      DDS) was prepared by intercalating the organic anion dodecylsulfate (DDS) in a Mg
      Al hydrotalcite (HT), and then characterized using several analytical techniques.
      A Mediterranean soil was selected for being a high-risk scenario of groundwater
      contamination by leaching of pollutants. The nanocomposite displayed enhanced
      affinity for the PAHs in water as compared to carbonate-hydrotalcite (HTCO(3))
      and its calcined product (HT500), and showed a high irreversibility of the
      adsorption process (hysteresis coefficient, H<0.15). The results revealed an
      increase of the pollutants retention in the soil by the addition of the
      nanocomposite that depended on the nanocomposite application rate and also on the
      hydrophobicity of each PAH. Accordingly, the use of HT-DDS as an amendment or
      barrier in contaminated soil is proposed for reducing the mobility of PAHs and,
      consequently, the adverse effect derived from rapid transport losses of the
      pollutants to the adjoining environmental compartments.

PMID- 22614028
TI  - Localization of transverse-sigmoid sinus junction using preoperative 3D computed
      tomography: application in retrosigmoid craniotomy.
AB  - In retrosigmoid craniotomy, neurosurgeons usually depend on surface landmarks and
      their experience to evaluate the position of transverse-sigmoid sinus junction
      (TSSJ) and place an appropriate initial burr-hole, which is not accurate each
      time because of variability in different craniums. The authors introduce a simple
      procedure based on 3D computed tomography (CT) to localize the TSSJ in
      retrosigmoid craniotomy. Eighteen patients who underwent retrosigmoid craniotomy
      were analyzed. On the internal view of skull in 3D CT image, a simulative burr
      hole was placed on the margin of transverse-sigmoid sinus groove junction. Then,
      on the external view of skull in 3D CT image, the center of the simulative burr
      hole was marked and a coordinate system was established based on a line connected
      the digastric point and the asterion. Then the coordinate of the burr-hole's
      center was measured in this coordinate system. In operation, the burr-hole was
      placed according to the coordinate measured previously and craniotomy was
      performed. The margin of TSSJ was exposed in each case. No damage of venous sinus
      was encountered. Post-operative skull base CT demonstrated a good match between
      the actual and predicted burr-hole and bone defects only existed along the cut
      line. This simple method could help in localizing the TSSJ and avoiding the risk
      of sinus injury and reducing the bone defect. It is sufficiently precise for
      practical application at surgical planning.

PMID- 22614029
TI  - Patient positioning variations to reduce dose to normal tissues during 3D
      conformal radiotherapy for high-risk prostate cancer.
AB  - BACKGROUND AND PURPOSE: The goal of this work was to assess optimal treatment
      positioning of 3D conformal radiotherapy (3DCRT) for high-risk prostate cancer
      patients. PATIENTS AND METHODS: Treatment plans of 25 patients in different
      patient positions were evaluated: with knee and ankle support (KAS) in the supine
      position and with a belly board (BB) in the prone position both with full (FB)
      and empty bladder (EB). Planning target volumes (PTVs) for pelvis, prostate and
      vesicles, prostate, and organs at risk (OARs) were delineated. Dose and
      overlapping volumes were evaluated. RESULTS: Overlapping volumes were
      significantly smaller with a FB than with an EB. No significant differences were
      found in overlapping volumes with respect to patient fixation systems, but the
      percentage values of dose to the OARs showed significantly better results
      employing KAS than a BB. A FB reduced the dose volumes to the OARs. Comparison
      with respect to circumference of abdomen (CA) showed significantly smaller
      overlapping at large CA in most of the cases. CONCLUSION: Supine position is
      suggested with KAS combined with a FB (especially in cases of larger CA) when
      using 3DCRT with planning technique modification for high-risk prostate cancer
      patients to reduce the dose of OARs, based on our results.

PMID- 22614030
TI  - Sequential approach to the synthesis of 'U and Z' shaped polycyclic heteroarenes.
AB  - The synthesis of three new classes of heteroarenes, built through the sequential
      fusion of naphthalene, benzo/naphtho[b]oxepine and thiochromene rings with pyran
      and pyrimidine ring systems to give 'U and Z' shaped structural frameworks is
      reported. The methodology is based on the synthesis of pyran fused intermediates,
      1-methylthio-3-oxo-5,6-dihydro-3H-benzo[f]chromene-2-carbonitrile (3), 4
      methylthio-2-oxo-5,6-dihydro-2H-benzo/naphtho[b]pyrano[2,3-d]oxepine-3
      carbonitriles (10, 20) and 4-methylthio-2-oxo-2,5-dihydrothiochromeno[4,3-b]pyran
      3-carbonitriles (15) from the reaction of 2-tetralone, benzo/naphtho[b]oxepin-5
      ones and thiochromen-4-ones with methyl 2-cyano-3,3-dimethylthioacrylate
      respectively. Further condensation of intermediates 3, 10, 20 and 15 with
      amidines led to the formation of tetracyclic 'U' shaped 4-amino-2-aryl-7,8
      dihydro-5-oxo-5H-naphtho[2,1-b]pyrimido[4,5-d]pyrans (8) and 'Z' shaped 4-amino-2
      aryl-5-oxo-12,13-dihydro-5H-benzo/naphtho[b]oxepino[5,4-b]pyrimido[4,5-d]pyrans
      (12, 22) and 4-amino-2-aryl-5-oxo-5,12-dihydrothiochromeno[4,3-b]pyrimido[4,5
      d]pyrans (17). Compound 12f forms a chain of dimers through N-HO interactions as
      indicated by the X-ray structure analysis, and the quantum chemical calculations
      performed at the MP2 level indicate that this interaction energy is 10 kJ mol(
      1).

PMID- 22614031
TI  - Chemoembolization with doxorubicin-eluting beads for unresectable hepatocellular
      carcinoma: five-year survival analysis.
AB  - PURPOSE: The purpose of this study was to report on the 5-year survival of
      hepatocellular carcinoma (HCC) patients treated with DC Bead loaded with
      doxorubicin (DEB-DOX) in a scheduled scheme in up to three treatments and
      thereafter on demand. MATERIALS AND METHODS: 173 HCC patients not suitable for
      curable treatments were prospectively enrolled (mean age 70.4 +/- 7.4 years).
      Child-Pugh (Child) class was A/B (102/71 [59/41 %]), Okuda stage was 0/1/2
      (91/61/19 [53.2/35.7/11.1 %]), and mean lesion diameter was 7.6 +/- 2.1 cm.
      Lesion morphology was one dominant <=5 cm (22 %), one dominant >5 cm (41.6 %),
      multifocal <=5 (26 %), and multifocal >5 (10.4 %). RESULTS: Overall survival at
      1, 2, 3, 4, and 5 years was 93.6, 83.8, 62, 41.04, and 22.5 %, with higher rates
      achieved in Child class A compared with Child class B patients (95, 88.2, 61.7,
      45, and 29.4 % vs. 91.5, 75, 50.7, 35.2, and 12.8 %). Mean overall survival was
      43.8 months (range 1.2-64.8). Cumulative survival was better for Child class A
      compared with Child class B patients (p = 0.029). For patients with dominant
      lesions <=5 cm 1-, 2-, 3-, 4-, and 5-year survival rates were 100, 95.2, 71.4,
      66.6, and 47.6 % for Child class A and 94.1, 88.2, 58.8, 41.2, 29.4, and 23.5 %
      for Child class B patients. Regarding DEB-DOX treatment, multivariate analysis
      identified number of lesions (p = 0.033), lesion vascularity (p < 0.0001),
      initially achieved complete response (p < 0.0001), and objective response (p =
      0.046) as significant and independent determinants of 5-year survival.
      CONCLUSION: DEB-DOX results, with high rates of 5-year survival for patients, not
      amenable to curative treatments. Number of lesions, lesion vascularity, and local
      response were significant independent determinants of 5-year survival.

PMID- 22614032
TI  - Percutaneous CT-guided biopsy of C3 vertebral body: modified approach for an old
      procedure.
AB  - Percutaneous biopsy of upper cervical vertebrae is challenging due to the various
      critical structures in the location and often requires difficult trajectory such
      as transoral or paramaxillary approaches. The purpose of this manuscript is to
      illustrate the utility of head rotation in creating a potential space for direct
      percutaneous access to C3 vertebral body for safe biopsy.

PMID- 22614033
TI  - N-acetylglucosaminyltransferase V negatively regulates integrin alpha5beta1
      mediated monocyte adhesion and transmigration through vascular endothelium.
AB  - Changes in the expression of glycosyltransferases that branch N-linked glycans
      are associated with many physiological and pathological events, such as cell
      adhesion, migration, proliferation and tumor cell malignancy. Here, the altered
      levels of N-acetylglucosaminyltransferase V (GnT-V) and its product beta(1,6)
      linked GlcNAc in monocytes were observed during inflammation. The effects of GnT
      V and aberrant N-linked beta(1,6) branching on monocyte adhesion through vascular
      endothelium and transmigration were investigated. During IFN-gamma-induced
      inflammation, adhesion and transendothelial migration of THP-1 monocytes were
      enhanced, and the levels of GnT-V and beta(1,6)-linked GlcNAc in THP-1 monocytes
      were significantly decreased. Expression of the GnT-V shRNA vector in THP-1 cells
      reversed the abnormal IFN-gamma-induced characteristics, indicating direct
      involvement of N-glycosylation in these biological effects. The enhanced adhesion
      and transendothelial migration were significantly inhibited by functional
      blockade with antibodies against integrin alpha5 or beta1 in IFN-gamma-induced
      and GnT-V knockdown THP-1 cells, demonstrating the involvement of integrin
      alpha5beta1 in the monocyte-endothelium interaction. However, IFN-gamma treatment
      and GnT-V knockdown in THP-1 cells lowered expression of N-linked beta(1,6)
      branching on integrin alpha5 and beta1, without affecting the total protein
      expression of the subunits. Decreased GnT-V expression caused marked enchancement
      of integrin-induced phosphorylation of focal adhesion kinase (FAK). The augmented
      FAK-mediated ERK phosphorylation and activation were observed in IFN-gamma
      induced THP-1 cells. Furthermore, ERK inhibitor pre-treatment nearly abrogated
      the highly elevated IFN-gamma-induced monocyte adhesion and transmigration,
      concomitant with reversal of the decrease in GnT-V and beta(1,6) branching. Our
      results demonstrate for the first time that decreased GnT-V activity due to
      inflammatory cytokine induction in human monocytes resulted in enchancement of
      integrin alpha5beta1-dependent monocyte-vascular endothelium adhesion and
      transmigration. Consequently, the activation of integrin caused elevation of FAK
      phosphorylation. These effects promoted FAK-mediated downstream signaling,
      including the ERK pathway, and indicate that GnT-V may be a potential therapeutic
      target for vascular inflammatory conditions.

PMID- 22614034
TI  - The potential for adaptation in a natural Daphnia magna population: broad and
      narrow-sense heritability of net reproductive rate under Cd stress at two
      temperatures.
AB  - The existence of genetic variability is a key element of the adaptive potential
      of a natural population to stress. In this study we estimated the additive and
      non-additive components of the genetic variability of net reproductive rate
      (R(0)) in a natural Daphnia magna population exposed to Cd stress at two
      different temperatures. To this end, life-table experiments were conducted with
      20 parental and 39 offspring clonal lineages following a 2 * 2 design with Cd
      concentration (control vs. 3.7 MUg Cd/L) and temperature (20 vs. 24  degrees C)
      as factors. Offspring lineages were obtained through inter-clonal crossing of the
      different parental lineages. The population mean, additive and non-additive
      genetic components of variation in each treatment were estimated by fitting an
      Animal Model to the observed R(0) values using restricted maximum likelihood
      estimation. From those estimates broad-sense heritabilities (H(2)), narrow-sense
      heritabilities (h(2)), total (CV(G)) and additive genetic coefficients of
      variation (CV(A)) of R(0) were calculated. The exposure to Cd imposed a
      considerable level of stress to the population, as shown by the fact that the
      population mean of R(0) exposed to Cd was significantly lower than in the control
      at the corresponding temperature, i.e. by 23 % at 20  degrees C and by 88 % at 24
      degrees C. The latter difference indicates that increasing temperature increased
      the stress level imposed by Cd. The H2 and CV(G) were significantly greater than
      0 in all treatments, suggesting that there is a considerable degree of genetic
      determination of R(0) in this population and that clonal selection could rapidly
      lead to increasing population mean fitness under all investigated conditions.
      More specifically, the H2 was 0.392 at 20  degrees C+Cd and 0.563 at 24  degrees
      C+Cd; the CV(G) was 30.0 % at 20  degrees C+Cd and was significantly higher
      (147.6 %) in the 24  degrees C+Cd treatment. Significant values of h(2) (= 0.23)
      and CV(A) (= 89.7 %) were only found in the 24  degrees C+Cd treatment,
      suggesting that the ability to produce more offspring under this stressful
      condition may be inherited across sexual generations. In contrast, in the less
      stressful 20  degrees C+Cd treatment the h(2) (0.06) and CV(A) (7.0 %) were very
      low and not significantly higher than zero. Collectively our data indicate that
      both the asexual and sexual reproduction phases in cyclic parthenogenetic D.
      magna populations may play a role in the long-term adaptive potential of Daphnia
      populations to chemical stress (with Cd as the current example) and that
      environmental variables which influence the stress level of that chemical may
      influence this adaptive potential (with temperature as current example).

PMID- 22614035
TI  - Effects of heavy metals on the expression of a zinc-inducible metallothionein-III
      gene and antioxidant enzyme activities in Crassostrea gigas.
AB  - Sequestration by metallothioneins and antioxidant defense are two kinds of
      important defense mechanisms employed by mollusks to minimize adverse effects
      caused by heavy metal contaminants in marine environment. In the present study, a
      novel metallothionein gene, CgMT-III, was cloned from Crassostrea gigas,
      consisting of eighteen conserved cysteine residues and encoding a MT III-like
      protein with two tandem beta domains. The expression level of CgMT-III transcript
      induced by zinc was much higher than that induced by cadmium exposure. It
      suggested that CgMT-III was perhaps mainly involved in homeostatic control of
      zinc metabolism, which was distinct from previously identified MTs in C. gigas.
      Among the tested antioxidant enzymes including superoxide dismutase (SOD),
      catalase (CAT), glutathione peroxidase (GPx), SOD and GPx showed varying up
      regulations in a tissue-specific manner, while CAT activities were inhibited in
      both gill and hepatopancreas from C. gigas exposed to heavy metals. It can be
      inferred that CgMT-III was mainly involved in zinc homeostasis, and CgMT-III gene
      together with CAT enzyme could be potential biomarkers to indicate heavy metal,
      especially zinc pollution in marine organisms.

PMID- 22614036
TI  - Effects of imidacloprid, a neonicotinoid pesticide, on reproduction in worker
      bumble bees (Bombus terrestris).
AB  - Bumble bees are important pollinators whose populations have declined over recent
      years, raising widespread concern. One conspicuous threat to bumble bees is their
      unintended exposure to trace residues of systemic neonicotinoid pesticides, such
      as imidacloprid, which are ingested when bees forage on the nectar and pollen of
      treated crops. However, the demographic consequences for bumble bees of exposure
      to dietary neonicotinoids have yet to be fully established. To determine whether
      environmentally realistic levels of imidacloprid are capable of making a
      demographic impact on bumble bees, we exposed queenless microcolonies of worker
      bumble bees, Bombus terrestris, to a range of dosages of dietary imidacloprid
      between zero and 125 MUg L(-1) and examined the effects on ovary development and
      fecundity. Microcolonies showed a dose-dependent decline in fecundity, with
      environmentally realistic dosages in the range of 1 MUg L(-1) capable of reducing
      brood production by one third. In contrast, ovary development was unimpaired by
      dietary imidacloprid except at the highest dosage. Imidacloprid reduced feeding
      on both syrup and pollen but, after controlling statistically for dosage,
      microcolonies that consumed more syrup and pollen produced more brood. We
      therefore speculate that the detrimental effects of imidacloprid on fecundity
      emerge principally from nutrient limitation imposed by the failure of individuals
      to feed. Our findings raise concern about the impact of neonicotinoids on wild
      bumble bee populations. However, we recognize that to fully evaluate impacts on
      wild colonies it will be necessary to establish the effect of dietary
      neonicotinoids on the fecundity of bumble bee queens.

PMID- 22614037
TI  - A mixture model of ductus venosus pulsatility index in screening for aneuploidies
      at 11-13 weeks' gestation.
AB  - OBJECTIVE: To assess the value of ductus venosus pulsatility index for veins (DV
      PIV) in screening for aneuploidies at 11-13 weeks' gestation. METHODS: Fetal DV
      PIV was measured in singleton pregnancies undergoing first-trimester screening
      for aneuploidies. In euploid (n = 44,756) and aneuploid (202 cases of trisomy 21,
      72 cases of trisomy 18 and 30 cases of trisomy 13) fetuses, DV PIV was best
      described by a mixture model of distributions. Performance of screening for
      aneuploidies by DV PIV alone and in combination with fetal nuchal translucency
      (NT) thickness and serum free beta-hCG and PAPP-A was estimated. RESULTS: In
      euploid pregnancies there was a bimodal distribution of DV PIV with a dominant
      crown-rump length (CRL)-dependent part, accounting for around 97% of cases in
      Caucasians and around 93% in Afro-Caribbeans, and a smaller CRL-independent
      distribution. In aneuploidies the dominant part was the CRL-independent
      distribution, which accounted for around 85% cases of trisomies 21 and 18 and 70%
      of cases of trisomy 13. In screening for trisomy 21 by maternal age, NT and
      biochemistry at a risk cutoff of 1 in 100, the detection rate was 89.7% and false
      positive rate was 2.74%; with addition of DV PIV, the values were 93.5 and 1.63%,
      respectively. CONCLUSIONS: Measurement of DV PIV improves the performance of
      first-trimester combined test for aneuploidies.

PMID- 22614041
TI  - Symptomatic postlaminectomy cerebrospinal fluid leak treated with 4-dimensional
      ultrasound-guided epidural blood patch.
AB  - BACKGROUND: A persistent cerebrospinal fluid leak after spinal surgery can be
      associated with both meningitis and/or pneumocephalus. Therefore, early active
      intervention is recommended with surgical exploration, lumbar subarachnoid drain,
      and less commonly epidural blood patch. In the absence of a ligamentum flavum,
      the use of high-resolution ultrasound (US) spine imaging enables real-time
      advancement of a Tuohy needle towards the dura and the precise injection of blood
      to cover the dural defect. METHODS: Six patients, after lumbar spine surgery with
      instrumentation and primary closure was complicated by incidental dural tears,
      developed severe symptomatic headaches that failed conservative therapy. All
      patients underwent US-guided epidural blood patch. Precise needle advancement to
      the dura was observed with US guidance, and 4-dimensional US scanning was used to
      confirm the expansion of blood over the dura in real time. RESULTS: All patients
      had symptomatic relief of their headaches and successful treatment of dural leaks
      using US-guided blood patch. CONCLUSIONS: Real-time US guidance allowed accurate
      positioning of the Tuohy needle and deposition of the epidural blood patch in the
      setting of a surgically removed ligamentum flavum. Further investigations are
      needed to confirm that an US-guided epidural blood patch may offer reliable
      symptomatic relief to postsurgical persistent cerebrospinal fluid leak and may
      serve as an intermediate step along a spectrum between conservative initial
      management and surgical reexploration.

PMID- 22614038
TI  - Sparassis crispa suppresses mast cell-mediated allergic inflammation: Role of
      calcium, mitogen-activated protein kinase and nuclear factor-kappaB.
AB  - Allergic inflammatory disease such as food allergy, asthma and atopic dermatitis
      are increasing worldwide. In this study, we investigated the effect of water
      extract of Sparassis crispa (WESC) Fr. (Aphyllophoromycetideae) on mast cell
      mediated allergic inflammation and the possible mechanisms of action. WESC
      inhibited compound 48/80-induced systemic anaphylaxis and serum histamine release
      in mice. WESC decreased immunoglobulin E (IgE)-mediated passive cutaneous
      anaphylaxis. Additionally, WESC reduced histamine release and intracellular
      calcium in human mast cells activated by phorbol 12-myristate 13-acetate (PMA)
      and calcium ionophore A23187. WESC decreased PMA and A23187-stimulated expression
      of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha,
      inlerleukin (IL)-6 and IL-1beta. The inhibitory effect of WESC on pro
      inflammatory cytokines was nuclear factor-kappaB, extracellular signal-regulated
      kinase and p38 mitogen-activated protein kinase-dependent. Our results suggest
      potential therapeutic application of WESC in allergic inflammatory diseases.

PMID- 22614042
TI  - Transient cardiac asystole during embolization of a caroticocavernous fistula.

PMID- 22614043
TI  - Local anesthetic-induced complete atrioventricular block during awake craniotomy.

PMID- 22614044
TI  - Cough and bronchospasm after rapid intravenous administration of phenytoin.

PMID- 22614045
TI  - Identification of a new protein biomarker for colorectal cancer diagnosis.
AB  - As one of the most common cancers, colorectal cancer (CRC) is a major public
      health issue worldwide. Thus, the identification of novel biomarkers to aid in
      the early diagnosis of CRC is crucial. The aim of the present study was to
      identify a novel protein biomarker for CRC, and to identify its structure. In
      this study, a total of 99 serum samples from 73 CRC patients and 26 healthy
      controls were collected and analyzed by SELDI-TOF-MS. The biomarkers were
      separated using HPLC and detected with MALDI-TOF-MS. The qualified peaks were
      ranked by p-value of non-parametric tests and the top 10 peaks displaying
      significant differences were selected. Among the 10 protein biomarkers, the
      concentration of a 3.9-kDa protein in the serum of the CRC patients was much
      lower than that in the healthy controls. Therefore, the 3.9-kDa protein was
      selected as a biomarker for CRC and its separation and purification were
      performed. The structure of the 3.9-kDa protein biomarker was determined by LC
      MS/MS, and was confirmed to be a fragment of serine/theonine kinase 4
      (MST1/STK4). The 3.9-kDa protein biomarker had high sensitivity and specificity
      for CRC, and its potential clinical application warrants further investigation.

PMID- 22614046
TI  - Relationships and context as a means for improving disease prevention and sexual
      health messages.

PMID- 22614047
TI  - Coronary branching patterns linked to polymorphisms in the hypoxia-inducible
      factor-1 alpha gene.

PMID- 22614048
TI  - Unfinished business in health care reform.

PMID- 22614049
TI  - From therapeutic nihilism to therapeutic success.

PMID- 22614050
TI  - Ionization energies and structures of lithium doped silicon clusters.
AB  - We report on a combined experimental and theoretical study of the ionization
      energies and structures of small lithium doped silicon clusters, SinLim with n =
      5-11 and m = 3-6. Photoionization efficiency curves are measured in the 4.68-6.24
      eV range and subsequently compared with calculated values of both vertical and
      adiabatic ionization energies for the lowest energy isomers obtained using
      density functional theory at the B3LYP/6-311+G(d) level. The evolution of the
      cluster geometries and ionization energies is studied as a function of the number
      of silicon and lithium atoms along the SinLi3 (n = 5-11) and Si8Lim (m = 1-6)
      series, respectively. For most studied sizes good agreement is found between the
      experimental and the calculated ionization energies for the lowest-energy isomer.
      In the SinLi3 (n = 5-11) series, positively charged lithium atoms surround a
      negatively charged silicon framework and mainly act as electron donors. Upon
      sequential lithium addition along the Si8Lim (m = 1-6) series, the Si8 framework
      deforms from a rhombic (m = 0, 1) over a tetracapped tetragon (m = 1-4) to a
      square antiprism (m = 4-6) structure. Subsequent addition of lithium implies the
      addition of excess electrons to the silicon framework, which is reflected in a
      decrease of the ionization energy with increasing lithium content. This decrease
      is non-monotonous and odd-even alternations, reflecting the higher stability of
      clusters with an even number of electrons, are observed. In addition, post
      threshold features in the experimental photoionization efficiency curves of
      SinLi3 (n = 8-11) may be related to the computed density of states of the
      corresponding lowest energy isomers. 

PMID- 22614051
TI  - The morphological structure of leaves and the dust-retaining capability of
      afforested plants in urban Guangzhou, South China.
AB  - PURPOSE: Air pollution is a serious health problem throughout the world,
      exacerbating a wide range of respiratory and vascular illnesses in urban areas.
      The mass artificial plantation is very helpful to absorb dust and reduce
      pollution for conservation of the urban environment. The foliar surface of plants
      is an important receptor of atmospheric pollutants. Therefore, selection of
      suitable plant species for urban environment is very important. METHODS: The dust
      retaining capability of urban trees in Guangzhou was determined at four different
      types of urban area, and the morphological traits of their leaves such as wax,
      cuticle, stomata, and trichomes were observed under a scanning electron
      microscope. RESULTS: It was determined that the dust-retaining capability of any
      given tree species is significantly different in the same place. Of the four
      studied tree species in the industrial area (IA) and commercial/traffic areas
      (CTA) type urban areas, the highest amounts of dust removed by Mangifera indica
      Linn was 12.723 and 1.482 g/m(2), respectively. However, in contrast, the
      equivalent maxima for Bauhinia blakeana is only 2.682 g/m(2) and 0.720 g/m(2),
      respectively. Different plant species have different leaf morphology. The leaf of
      M. indica has deep grooves and high stomata density which are in favor of dust
      retained, and thus, their dust-retained capability is stronger, while B. blakeana
      has the cells and epicuticular wax with its stomata arranging regularly,
      resulting in poor dust catching capability. Leaf size was also shown to be
      related to dust capture for the four studied tree species. CONCLUSIONS: The dust
      removal capacity of individual tree species should be taken into account in the
      management of greening plantation in and around an urban area. It was also shown
      that temporal variation in dust accumulation occurred over the 28-day observation
      period and this was discussed. Furthermore, spatial contrasts in dust
      accumulation were evidenced by the data. This reflected the differing pollution
      loadings of the four urban-type areas. The highest amount of dust accumulation
      was associated with the industrial area in which shipyard and steelworks occurred
      whilst the lowest dust accumulation was associated with the grounds of the
      University which was the control area.

PMID- 22614052
TI  - Removal of heavy metal ions from wastewater by a novel HEA/AMPS copolymer
      hydrogel: preparation, characterization, and mechanism.
AB  - This study aims to synthesize 2-hydroxyethyl acrylate (HEA) and 2-acrylamido-2
      methylpropane sulfonic (AMPS) acid-based hydrogels by gamma radiation and to
      investigate their swelling behavior and heavy metal ion adsorption capabilities.
      The copolymer hydrogels prepared were characterized via scanning electron
      microscopy, Fourier transformed infrared spectra, thermal gravimetric analysis,
      and X-ray photoelectron spectroscopy. The research showed that the copolymer
      hydrogel was beneficial for permeation due to its porous structure. In addition,
      the experimental group A-2-d [70 % water volume ratio and (n (AMPS)/n (HEA))
      =1:1] was an optimal adsorbent. The optimal pH was 6.0 and the optimal
      temperature was 15  degrees C. Pb(2+), Cd(2+), Cu(2+), and Fe(3)+ achieved
      adsorption equilibriums within 24 h, whereas Cr(3+) reached equilibrium in 5 h.
      Pb(2)+, Cd(2+), Cr(3+), and Fe(3+) maximum load capacity was 1,000 mg L(-1),
      whereas the Cu(2+) maximum capacity was 500 mg L(-1). The priority order in the
      multicomponent adsorption was Cr(3+)>Fe(3+)>Cu(2+)>Cd(2+)>Pb(2+). The adsorption
      process of the HEA/AMPS copolymer hydrogel for the heavy metal ions was mainly
      due to chemisorption, and was only partly due to physisorption, according to the
      pseudo-second-order equation and Langmuir adsorption isotherm analyses. The
      HEA/AMPS copolymer hydrogel was confirmed to be an effective adsorbent for heavy
      metal ion adsorption.

PMID- 22614053
TI  - Multi-level influences on childhood obesity in Sweden: societal factors, parental
      determinants and child's lifestyle.
AB  - BACKGROUND: Swedish school children living in rural areas and in areas with low
      education are at excess risk of becoming overweight. This study examines
      influences of societal and individual characteristics (children and their
      parents) on prevalence of overweight and obesity, in a national sample of 7-9
      year-old children. METHOD: Anthropometric and lifestyle data were collected in a
      nationally representative sample of 3636 Swedish children. Overweight and obesity
      (International Obesity Task Force (IOTF)) data were analyzed in relation to
      lifestyle factors, parental weight, education and breast-feeding. RESULTS: The
      prevalence of overweight was 15.6% including 2.6% obese. Urbanization level and
      parental characteristics (weight status and education) were related to risk of
      overweight. Overall less favorable lifestyle characteristics were observed in
      rural areas and for children of low/medium educated mothers. Boys had greater
      risk of obesity in semi-urban and rural areas but this was not true for girls.
      For children's overweight, the living area effect was attenuated in multivariate
      analysis, while there was an association with origin of parents, high parental
      weight and medium maternal education. For obesity, the living area effect
      remained in boys while having two non-Nordic parents predicted obesity in girls.
      Parental weight status was associated with obesity in both girls and boys.
      CONCLUSION: Individual and societal factors influence children's weight status,
      and parental weight status is a strong determinant. Including overweight and
      obese parents in future health promoting interventions could be a strategy to
      prevent children from becoming overweight, but identifying those parents may
      prove difficult. To ensure reaching children with the greatest needs, targeting
      high risk areas might be a more effective approach.

PMID- 22614054
TI  - Association of midlife obesity and cardiovascular risk with old age frailty: a 26
      year follow-up of initially healthy men.
AB  - OBJECTIVE AND HYPOTHESIS: To investigate whether old age frailty is predicted by
      midlife overweight/obesity and cardiovascular disease (CVD) risk. DESIGN:
      Longitudinal observational study (the Helsinki Businessmen Study). SUBJECTS: In
      their midlife in 1974, 1815 initially healthy men (mean age 47 years) were
      clinically investigated, whereupon their weight status (normal weight < 25 kg m(
      2), overweight 25 <= body mass index <30 kg m(-2) and obese >= 30 kg m(-2)), CVD
      risk factors and a composite risk score (%) of coronary artery disease (CAD) were
      assessed. After a 26-year follow-up in 2000, when 425 men had died, the frailty
      status of survivors (80.9%, n=1125, mean age 73 years) was assessed using a
      postal questionnaire including the RAND-36/SF-36 instrument. Phenotypic criteria
      were used to define frailty, and according to these criteria, 40.0% (n=450),
      50.4% (n=567) and 9.6% (n=108) were classified as not frail, prefrail and frail,
      respectively. Risks are presented as odds ratios (OR) with 95% confidence
      intervals (CI). RESULTS: Compared with normal weight, the development of frailty
      was significantly higher among those men who were overweight or obese in midlife,
      with fully adjusted ORs (95% CI) of 2.06 (1.21-3.52) and 5.41 (1.94-15.1),
      respectively. Even the development of prefrailty was significantly increased with
      midlife overweight (OR 1.39; 95% CI, 1.03-1.87) and obesity (OR 2.96; 95% CI,
      1.49-5.88). Age-adjusted composite CAD score in midlife predicted similarly 26
      year total mortality (OR per 1% increase:1.16; 95% CI, 1.08-1.24) and development
      of frailty (OR 1.16; 95% CI, 1.02-1.33). CONCLUSION: Overweight/obesity and
      higher CAD risk in midlife were associated with frailty 26 years later.
      Preventing old age frailty should be recognized as an important goal of obesity
      and CVD risk control.

PMID- 22614055
TI  - FTO expression is regulated by availability of essential amino acids.
AB  - Genome-wide association studies have revealed that single nucleotide
      polymorphisms in fat mass and obesity-associated transcript (FTO) are robustly
      associated with body mass index and obesity. Expression of Fto in the
      hypothalamic arcuate nucleus is bidirectionally regulated as a function of
      nutritional status; decreasing following a 48-h fast and increasing after 10-week
      exposure to a high-fat diet. Here, we utilize an in vitro approach to determine
      which nutrients could regulate FTO levels at a cellular level. Using mouse and
      human cell lines, we find that FTO levels are not influenced by serum starvation.
      We demonstrate, however, that both glucose and total amino-acid deprivation
      regulates FTO expression. In particular, we have found that FTO mRNA and protein
      levels are dramatically downregulated by total amino-acid deprivation in mouse
      hypothalamic N46 cells, mouse embryonic fibroblasts and in human HEK293 cells.
      The drop rate of Fto mRNA is faster than its rate of natural degradation,
      pointing to regulation at the transcriptional level, which is reversible upon
      amino-acid replacement. Strikingly, this downregulation was seen only with
      essential amino-acid deficiency and not nonessential amino acids. These data
      suggest that FTO might have a role in the sensing of essential amino-acid
      availability.

PMID- 22614056
TI  - Copeptin, a marker of vasopressin, in abdominal obesity, diabetes and
      microalbuminuria: the prospective Malmo Diet and Cancer Study cardiovascular
      cohort.
AB  - BACKGROUND: High plasma copeptin (copeptin), the C-terminal fragment of arginine
      vasopressin pro-hormone, has been associated with the metabolic syndrome (MetS),
      diabetes mellitus (DM) development and nephropathy. Here we tested whether
      elevated copeptin level is associated with later development of the MetS, its
      individual components and microalbuminuria. METHODS: We analysed copeptin at
      baseline (1991-1994) in the population-based Malmo Diet and Cancer Study
      cardiovasular cohort and re-examined 2064 subjects 15.8 years later (mean age
      72.8 years, 59% women) with oral glucose tolerance test and measurement of MetS
      and its individual components. RESULTS: After age and sex adjustment, increasing
      quartiles of copeptin at baseline (the lowest quartile as reference) were
      associated with MetS (P for trend=0.008), incident abdominal obesity (P for
      trend=0.002), DM (P for trend=0.001) and microalbuminuria (P for trend=0.002).
      After additional adjustment for all the MetS components at baseline, increasing
      copeptin quartiles predicted incident abdominal obesity (odds ratios 1.55, 1.30
      and 1.59; P for trend=0.04), DM (odds ratios 1.18, 1.32 and 1.46; P for
      trend=0.04) and microalbuminuria (odds ratios 1.05, 1.08 and 1.65; P for
      trend=0.02) but not MetS (P for trend=0.19) at the reexamination. Further, the
      relationship between copeptin and microalbuminuria was independent of baseline C
      reactive protein, incident DM and incident hypertension. CONCLUSION: Copeptin
      independently predicts DM and abdominal obesity but not the cluster of MetS.
      Apart from predicting DM and abdominal obesity, elevated copeptin signals
      increased risk of microalbuminuria. Interestingly, the association between
      copeptin and later microalbuminuria was independent of both prevalent and
      incident DM and hypertension. Our findings suggest a relationship between a
      dysregulated vasopressin system and cardiometabolic risk, which could have
      implications for risk assessment and novel preventive treatments.

PMID- 22614058
TI  - Lipopolysaccharide-induced chorioamnionitis is confined to one amniotic
      compartment in twin pregnant sheep.
AB  - BACKGROUND: Chorioamnionitis is a major risk factor for preterm birth in
      multifetal pregnancies. However, there is little clinical data whether
      chorioamnionitis is restricted to one amniotic compartment in multifetal
      pregnancies. OBJECTIVE: To explore whether chorioamnionitis is confined to the
      exposed compartment and does not cross to the unaffected fetus in twin pregnancy.
      METHODS: In twin pregnant sheep, one of the twins was exposed to either 2 or 14
      days of intra-amniotic lipopolysaccharide (LPS) while the co-twin was exposed to
      either 2 or 14 days of intra-amniotic saline (n = 3 for each exposure).
      Singletons were included in this study to compare the grade of inflammation with
      twins. All fetuses were delivered at 125 days of gestation (term = 150 days).
      Chorioamnionitis was confirmed by histological examination. Lung inflammation was
      assessed by cell count in bronchoalveolar lavage. Lung compliance was assessed at
      40 cm H(2)O. Results were compared using analysis of variance (ANOVA) with a post
      hoc Tukey analysis. RESULTS: Inflammation in placenta, membranes and lung of LPS
      exposed twins was significantly higher after 2 and 14 days of exposure when
      compared to the saline-exposed co-twins. Lung compliance in LPS-exposed twins was
      significantly increased after 14 days when compared to saline-exposed co-twins.
      Intrauterine LPS exposure increased lung compliance and inflammation in the
      membranes, placenta and lung to the same extent in twins as in singletons.
      CONCLUSION: In twin pregnant sheep, inflammation of the membranes, placenta and
      fetal lung was strictly limited to the exposed fetus in the amniotic compartment
      in which the LPS was injected.

PMID- 22614059
TI  - Emergency admissions for diabetes fall by almost 7% in integrated care pilot
      scheme.

PMID- 22614057
TI  - Maternal obesity downregulates microRNA let-7g expression, a possible mechanism
      for enhanced adipogenesis during ovine fetal skeletal muscle development.
AB  - BACKGROUND: Obesity in women of childbearing age is increasing at an alarming
      rate. Growing evidence shows that maternal obesity induces detrimental effects on
      offspring health, including pre-disposition to obesity. We have shown that
      maternal obesity increases fetal intramuscular adipogenesis at mid-gestation.
      However, the mechanisms are poorly understood. MicroRNAs (miRNAs) regulate mRNA
      stability. We hypothesized that maternal obesity alters fetal muscle miRNA
      expression, thereby influencing intramuscular adipogenesis. METHODS: Non-pregnant
      ewes received a control diet (Con, fed 100% of National Research Council (NRC)
      recommendations, n=6) or obesogenic diet (OB; 150% NRC recommendations, n=6) from
      60 days before to 75 days after conception when the fetal longissimus dorsi (LD)
      muscle was sampled and miRNA expression analyzed by miRNA microarray. One of
      miRNAs with differential expression between Con and OB fetal muscle, let-7g, was
      further tested for its role in adipogenesis and cell proliferation in C3H10T1/2
      cells. RESULTS: A total of 155 miRNAs were found with a signal above 500, among
      which, three miRNAs, hsa-miR-381, hsa-let-7g and bta-miR-376d, were
      differentially expressed between Con and OB fetuses, and confirmed by
      quantitative real-time PCR (QRT-PCR) analyses. Reduced expression of miRNA let
      7g, an abundantly expressed miRNA, in OB fetal muscle was correlated with higher
      expression of its target genes. Overexpression of let-7g in C3H10T1/2 cells
      reduced their proliferation rate. Expression of adipogenic markers decreased in
      cells overexpressing let-7g, and the formation of adipocytes was also reduced.
      Overexpression of let-7g decreased expression of inflammatory cytokines.
      CONCLUSION: Fetal muscle miRNA expression was altered due to maternal obesity,
      and let-7g downregulation may enhance intramuscular adipogenesis during fetal
      muscle development in the setting of maternal obesity.

PMID- 22614060
TI  - Greeks feel effects of drug shortages caused by austerity measures.

PMID- 22614061
TI  - NHS "hack day" will reward apps and software tools that help patients and
      doctors.

PMID- 22614062
TI  - Metformin enhances the antiproliferative and apoptotic effect of bicalutamide in
      prostate cancer.
AB  - BACKGROUND: Prostate cancer incidence and mortality vary dramatically by
      geographical location. Both are higher in developed countries. Some attribute
      this to westernized lifestyles of high-energy diets and limited physical activity
      with consequent obesity. Obesity and obesity-related diseases like diabetes cause
      hyperinsulinaemia, which upregulates pro-survival cell signalling. Previous work
      revealed diet-induced hyperinsulinaemia enhances prostate cancer xenograft growth
      in vivo. Metformin, an antidiabetic medication, reduces hyperinsulinaemia and
      also exhibits antineoplastic properties. Herein, we assess the potential additive
      benefit of combining bicalutamide antiandrogen therapy with metformin, in vitro
      and in vivo. METHODS: Using clonogenic assays, we assessed the effect of
      bicalutamide and/or metformin on clonogenicity in prostate cancer cell lines.
      Western blot and cell cycle analyses were used to elucidate mechanisms of
      interaction between the drugs in androgen receptor (AR)-positive (LNCaP) and AR
      negative (PC3) cell lines. The combination treatment regimen was assessed in vivo
      using an LNCaP murine xenograft model. RESULTS: Micromolar bicalutamide or
      millimolar metformin caused a significant dose-dependent reduction in
      clonogenicity (P<0.001). Combination treatment further significantly reduced
      clonogenicity (P<0.005) with greater effects in AR-positive cells. Western blot
      and cell cycle analyses suggested differing mechanisms of interaction in AR
      positive and -negative cell lines. Following combination treatment, LNCaP cells
      exhibited an altered cell proliferation (decreased phospho mammalian target of
      rapamycin expression) and perturbed cell cycle kinetics (G1/S cell cycle arrest).
      PC3 cells showed evidence of enhanced apoptosis (increased Bcl-2-associated X
      protein and decreased total caspase 3 expression). Markedly diminished tumour
      growth occurred following combination treatment in vivo (P<0.001). CONCLUSIONS:
      Combining bicalutamide and metformin significantly reduces prostate cancer cell
      growth further than either monotherapy. In AR-positive cells, this effect
      appeared to be mediated by reducing proliferation rates, whereas in AR-negative
      cells the combination treatment appeared to promote apoptosis. This combination
      drug regimen may improve prostate-cancer-specific survival by the direct
      antineoplastic properties outlined.

PMID- 22614065
TI  - Polymorphs of LiFeSO4F as cathode materials for lithium ion batteries - a first
      principle computational study.
AB  - We have investigated polymorphs of LiFeSO4F, tavorite and triplite, which have
      been reported as cathode materials for lithium ion batteries. The predicted
      voltages are 3.64 and 3.90 V for tavorite and triplite, respectively, which
      agreed excellently with experimental data. It is found that the lithiated states
      (LiFeSO4F) of the polymorphs are almost degenerate in energy. The difference in
      voltage is mainly due to the difference in the stabilities of the delithiated
      states (FeSO4F). This is rationalized by the Fe(3+)-Fe(3+) repulsion in the edge
      sharing geometry of the triplite structure. 

PMID- 22614064
TI  - Origin of a prenatal mosaic supernumerary neocentromeric derivative chromosome 13
      determined by QF-PCR.
AB  - Neocentromeres are mitotically stable human derivative centromeres without alpha
      satellite DNA which are able to provide stability to rearranged chromosome
      fragments that would otherwise be acentric and rapidly lost. A female fetus was
      found to be mosaic for a supernumerary marker chromosome:
      47,XX,+mar[3]/46,XX[36]. The marker was identified by fluorescence in situ
      hybridization and G-band as an inversion duplication of 13q21->13qter, with a
      neocentromere present at 13q21, in approximately 9% of colonies examined.
      Parental blood karyotypes were normal. QF-PCR performed on blood samples from
      both parents and the second amniotic fluid sample showed evidence of a second
      maternal allele at markers D13S258 (13q21) and D13S628 (13q31-q32), indicating
      formation at maternal meiosis I/II. This is the first reported case where the
      detection and origin of a low-level mosaic prenatal neo(13) were confirmed by QF
      PCR.

PMID- 22614066
TI  - Synthesis and evaluation of novel caged DNA alkylating agents bearing 3,4
      epoxypiperidine structure.
AB  - Previously, we reported that the 3,4-epoxypiperidine structure, whose design was
      based on the active site of DNA alkylating antitumor antibiotics, azinomycins A
      and B, possesses prominent DNA cleavage activity. In this report, novel caged DNA
      alkylating agents, which were designed to be activated by UV irradiation, were
      synthesized by the introduction of four photo-labile protecting groups to a 3,4
      epoxypiperidine derivative. The DNA cleavage activity and cytotoxicity of the
      caged DNA alkylating agents were examined under UV irradiation. Four caged DNA
      alkylating agents showed various degrees of bioactivity depending on the
      photosensitivity of the protecting groups.

PMID- 22614067
TI  - In pulmonary sclerosing hemangioma expression of beta-catenin, Axin, and C-myc
      differs between the two cell types.
AB  - Previous studies have shown that pulmonary sclerosing hemangioma is a tumor
      derived from primitive respiratory epithelium, but its character and the
      differentiation status of the two cell types (polygonal and cuboidal) composing
      the lesion are still controversial. We hypothesize that the polygonal cells are
      immature compared with cuboidal cells and have higher proliferative activity. To
      further study this question, we examined the expression of beta-catenin, Axin,
      and C-myc by immunostaining in 45 primary sclerosing hemangioma (PSH) specimens.
      The two cell types were captured by laser capture microdissection from 28 PSH
      specimens, and total RNA was extracted. Messenger RNA (mRNA) expression of Axin
      and C-myc was examined by reverse transcription polymerase chain reaction (RT
      PCR). By immunostaining, beta-catenin was predominantly strongly expressed on the
      cell membrane of cuboidal cells, while in polygonal cells, beta-catenin was
      predominantly expressed in the cytoplasm and significantly decreased on cell
      membranes. Axin was expressed in cuboidal cells in 93 % of our 45 cases, but only
      expressed in 18 % of these in polygonal cells. C-myc expression in polygonal
      cells was significantly stronger than in cuboidal cells (P < 0.05). RT-PCR showed
      that the expression level of Axin mRNA in cuboidal cells was significantly higher
      than in polygonal cells (P < 0.05), and expression level of C-myc mRNA in
      polygonal cells was significantly higher than in cuboidal cells (P < 0.05).The
      two PHS cell types have distinct expression of beta-catenin, Axin, and C-myc,
      suggesting that their differentiation status may be different. The higher
      expression of C-myc in polygonal cells suggests that these cells might have
      higher proliferative activity.

PMID- 22614068
TI  - Neurodegeneration in ataxia telangiectasia: what is new? What is evident?
AB  - This article summarizes evident and recent findings on the characteristics of the
      neurological phenotype in ataxia telangiectasia (AT), reviews neuropathological
      and neuroradiological findings, and outlines therapeutic treatment options. In
      addition, this review offers an overview of current hypotheses on mechanisms of
      neurodegeneration in AT and discusses their relevance in clinical neurology. The
      obvious features of neurodegeneration in AT-cerebellar ataxia and dysarthia-are
      accompanied by a variety of further disabling disease symptoms. Review of the
      literature outlines a complex pattern of central nervous degeneration in AT that
      might have been underestimated so far. Neurodegeneration in AT is closely related
      to the absence or partial lack of the ataxia telangiectasia-mutated (ATM) kinase.
      ATM is a central player in maintaining cellular homeostasis. Systemic review of
      the literature reveals a subset of cellular targets hypothesized to count
      responsible for degeneration in ATM-deficient neurons. Further systematic
      cliniconeurological, pathoanatomical, and neuroradiological studies are required
      to understand the structural basis of this neurodegenerative disease. This better
      understanding has implications for the treatment of AT patients. Second,
      biochemical and molecular biological studies aimed at deciphering the
      pathomechanisms of this progressive disorder are necessary for the development of
      promising future therapies.

PMID- 22614069
TI  - Glycoprotein hormone in the pituitary of hagfish and its evolutionary
      implications.
AB  - The pituitary gland is present in all vertebrates, from agnathans (jawless
      vertebrates) to mammals, but not in invertebrates. Reproduction in gnathostomes
      (jawed vertebrates) is controlled by two pituitary gonadotropins (GTHs),
      luteinizing hormone and follicle-stimulating hormone, which are part of the
      pituitary glycoprotein hormone (GPH) family. Hagfishes, which lack both jaws and
      vertebrae, are considered the most primitive vertebrate known, living or extinct.
      Accordingly, they are of particular importance in understanding the evolution of
      the pituitary GPHs and their functions related to vertebrate reproduction.
      Nevertheless, key elements of the reproductive endocrine system in hagfish have
      yet to be elucidated. Our current report has revealed the first identification of
      a functional GPH composed of two subunits that possess gonadotropic action at the
      pituitary of brown hagfish. It seems most likely that an ancestral GPH gave rise
      to only one GTH in hagfish pituitary and that multiplicity of GPHs arose later
      during the early evolution of gnathostomes. This paper briefly summarizes the
      latest findings on the hagfish GPH from an evolutionary point of view.

PMID- 22614070
TI  - Rapid microRNA detection using power-free microfluidic chip: coaxial stacking
      effect enhances the sandwich hybridization.
AB  - We present a new method for rapid microRNA detection with a small volume of
      sample using the power-free microfluidic device driven by degassed PDMS. Target
      microRNA was detected by sandwich hybridization taking advantage of the coaxial
      stacking effect. This method allows us to detect miR-21 in 20 min with a 0.5 MUL
      sample volume at a limit of detection of 0.62 nM. Since microRNAs can act as
      cancer markers, this method might substantially contribute to future point-of
      care cancer diagnosis.

PMID- 22614071
TI  - Inhibition of the mTOR/S6K signal is necessary to enhance fluorouracil-induced
      apoptosis in gastric cancer cells with HER2 amplification.
AB  - The purpose of this study was to explore the effect of trastuzumab in enhancing
      the activity of chemotherapeutic agents and the molecular basis of this effect.
      Two gastric cancer cell types with HER2 amplification, one sensitive (NCI-N87)
      and one insensitive (MKN-7) to trastuzumab, were tested for the effects of
      trastuzumab on cell growth and cell signaling using MTS assay and western
      blotting, respectively. Interaction between trastuzumab and chemotherapeutic
      agents (fluorouracil, doxorubicin, cisplatin and paclitaxel) was evaluated by the
      combination index (CI). Fluorouracil-induced apoptosis was evaluated using
      western blot for poly (ADP-ribose) polymerase (PARP). Trastuzumab decreased
      phosphorylation of S6K, showed synergistic effect with fluorouracil or
      doxorubicin, and increased fluorouracil-induced apoptosis in NCI-N87 cells, but
      not in MKN-7 cells. While the mTOR inhibitor everolimus enhanced fluorouracil
      induced apoptosis in both HER2-amplified cell lines, this was not the case in the
      gastric cancer cell lines without HER2 amplification. Consistently, while the
      EGFR/HER2 inhibitor Cl-387,785 inhibited cell growth of MKN-7, this growth
      inhibition did not accompany decrease in phosphorylation of S6K, and the compound
      did not enhance fluorouracil-induced apoptosis. In summary, inhibition of the
      mTOR/S6K signal may be a key molecular event in enhancing fluorouracil-induced
      apoptosis specifically in gastric cancer cells with HER2 amplification. mTOR
      inhibitors may therefore be attractive alternative drugs in gastric cancers with
      HER2 amplification regardless of their sensitivity to trastuzumab.

PMID- 22614072
TI  - Comparative study of safety and outcomes of single-port access versus
      conventional laparoscopic colorectal surgery.
AB  - BACKGROUND: Single-port access (SPA) offers cosmetic advantages in addition to
      the well-recognised benefits of conventional multi-port laparoscopic (CL)
      surgery, and can be carried out using standard straight instruments. We report
      the outcomes of our early experience with SPA colorectal resections in comparison
      with CL surgery. METHODS: We compared the following data, patient
      characteristics, operating time, morbidity, operative mortality, length of
      hospital stay and tumour variables, of patients who underwent SPA right, left,
      sigmoid and total colon resections, as well as high anterior resections and
      panproctocolectomies, with that of patients who underwent equivalent conventional
      laparoscopic (CL) operations. The 40 SPA and 78 CL patients studied underwent
      surgery between February 2008 and September 2011. RESULTS: There was no
      difference between the SPA and CL operations, as regards the patient's sex (55.0
      vs. 62.8% males, p = 0.411), comorbidity (ASA I 10.0 vs. 12.8%; ASA II 57.5 vs.
      59.0%; ASA III 32.5 vs. 25.6%; ASA IV 0 vs. 2.6%, p = 0.722) and body mass index
      (26.2 vs. 28.0 kg/m(2), p = 0.073). However, SPA patients were younger (mean age
      54.1 vs. 64.8 years, p = 0.001), and malignancy was a less common indication for
      surgery (25.0 vs. 71.8%, p < 0.001). There were no conversions to open surgery,
      and one death occurred in the CL group (1.3%). Mean operating time (162 vs. 170
      min, p = 0.547), median post-operative hospital stay (4 vs. 4 days, p = 0.255)
      and morbidity (7.5 vs. 12.8%, p = 0.538) were comparable. CONCLUSIONS: SPA
      laparoscopic surgery appears safe in the hands of experienced laparoscopic
      surgeons, with no increase in operating time, length of stay, morbidity and
      mortality. Selection of patients with indications for surgery for benign disease
      may be of importance to ensure an oncologically safe initial uptake of SPA
      colorectal practice.

PMID- 22614073
TI  - Proteomic analysis of matrix of dental biofilm formed under dietary carbohydrate
      exposure.
AB  - To evaluate whether protein changes in extracellular matrix of dental biofilm are
      a unique property of sucrose, this in situ study was conducted using as active
      control glucose and fructose, the sucrose monosaccharide constituents. Proteins
      were analyzed by two-dimensional electrophoresis followed by LC-MS/MS after
      trypsin digestion. Absence or lower abundance of calcium-binding proteins and
      higher abundance of prolactin-induced proteins were found in biofilm formed in
      the presence of sucrose or its monosaccharide constituents compared with water,
      the negative control group. The data suggest that besides sucrose, other dietary
      carbohydrates may also provoke a change in the protein profile of extracellular
      matrix of dental biofilm formed.

PMID- 22614074
TI  - White matter hyperintensities are an independent predictor of physical decline in
      community-dwelling older people.
AB  - BACKGROUND: Ageing is associated with physical disability, but little is known
      about the influence of white matter hyperintensities (WMHs) on physical function
      decline in older people. OBJECTIVE: To investigate the role of WMHs as a
      predictor of decline in physical function in cognitively intact older people.
      METHODS: 287 community-dwelling people aged 70-90 years underwent the
      Physiological Profile Assessment (PPA) and assessments of total and regional WMH
      volumes, cognitive function and comorbidities. Participants underwent
      reassessment of the PPA 12 months later, and those in the top quartile for
      increases in PPA scores over the year were regarded as having declined
      physically. RESULTS: Multivariate logistic regression analyses revealed that
      people with WMH volumes in the 4th quartile showed greater physical decline (odds
      ratio 3.02, 95% confidence interval 1.02-8.95) while controlling for age,
      baseline physical function, general health, physical activity and cognitive
      function. Subsequent univariate analyses indicated that WMHs in the deep fronto
      parietal and periventricular parieto-occipital regions had the strongest
      associations with physical decline. CONCLUSIONS: These findings indicate that
      WMHs are an independent predictor of decline in physical function and suggest
      that interventions that focus on preventing the development or progression of
      white matter lesions may help preserve physical function in older people.

PMID- 22614076
TI  - Refining zebrafish housing for more reliable results.

PMID- 22614077
TI  - Harnessing brain signals to move paralyzed limbs.

PMID- 22614079
TI  - High anxiety linked to tumor growth in mice.

PMID- 22614080
TI  - Gut bacteria may modify obesity risk.

PMID- 22614082
TI  - Experimental biology 2012.

PMID- 22614083
TI  - Mice may become caught in nesting material.

PMID- 22614084
TI  - The ever-adaptable anole.

PMID- 22614085
TI  - Reporting requirements for finches. Response to protocol review scenario: finches
      should be included.

PMID- 22614086
TI  - Reporting requirements for finches. Response to protocol review scenario: not
      now; maybe later.

PMID- 22614087
TI  - Reporting requirements for finches.

PMID- 22614088
TI  - Reporting requirements for finches. Response to protocol review scenario: when in
      doubt!

PMID- 22614089
TI  - Reporting requirements for finches. Response to protocol review scenario: a word
      from USDA.

PMID- 22614090
TI  - Unassisted blood collection from unanesthetized rats and gerbils.
AB  - Blood collection is a common procedure in animal research. This column describes
      humane methods of collecting blood from the rat and the gerbil that can be
      carried out by a single person on an awake animal.

PMID- 22614091
TI  - Generation time of zebrafish (Danio rerio) and medakas (Oryzias latipes) housed
      in the same aquaculture facility.
AB  - The zebrafish and the medaka are both important model organisms in biomedical
      research. Both species are frequently characterized as having a generation time
      of approximately 2-4 months, but the precise onset of sexual maturity and the
      variability of reproductive success with age have not been previously examined.
      The authors studied reproduction in replicate groups of wild-type zebrafish
      (strain AB) and medakas (strain Cab) that were maintained together in the same
      aquaculture system. Length, weight and survival of the fish were measured and
      recorded once per week. Reproductive success and viability of offspring were also
      evaluated. Both zebrafish and medakas began producing viable embryos within 60 d
      post-fertilization. These findings show that it is possible to successfully
      maintain populations of both species within the same research infrastructure
      without compromising reproductive success or embryo viability.

PMID- 22614092
TI  - Considerations for importing live genetically modified mice from academic
      laboratories.
AB  - Genetically modified mice have been an invaluable tool for the study of gene
      function in an intact biological system. Researchers frequently obtain
      genetically modified mice from other academic institutions. This form of
      collaboration between laboratories comes with a unique set of challenges, and a
      clear set of guidelines for navigating the process has yet to be defined. The
      author provides suggestions for how to initiate an exchange of animal resources
      and steps for ensuring a successful collaboration. Both parties should be clear
      about their expectations. The importing lab should prepare in advance for
      potential animal health considerations and breeding and colony management
      strategies prior to importation. The number, gender, age and genotype of the
      imported animals should be confirmed as soon as possible by the importing lab. It
      is in the best interest of all parties to be courteous, forthright and thorough
      when sharing animal resources so that everyone can benefit from the resulting
      research.

PMID- 22614093
TI  - Metabolic caging for animal research.

PMID- 22614094
TI  - An exotic career.

PMID- 22614095
TI  - Simulated microgravity decreases apoptosis in fetal fibroblasts.
AB  - Space travel is a major challenge for human beings. Especially, the mechanisms
      through which space conditions might alter animal development have been
      questioned for a long time. The two major physical stress factors that are of
      relevance in this context are space radiation and weightlessness. While it has
      been extensively shown that high doses of ionizing radiation induce deleterious
      effects on embryonic development, so far, little is known about the potential
      harmful effects of radiation in combination with microgravity on the developing
      organism. In the present study, we investigated the effects of simulated
      microgravity on irradiated STO mouse fetal fibroblast cells using a random
      positioning machine (RPM). Radiation-induced cell cycle changes were not affected
      when cells were subjected to simulated microgravity for 24 h. Moreover, no
      morphological differences were observed in irradiated samples exposed to
      simulated microgravity compared to cells that were exclusively irradiated.
      However, microgravity simulation significantly decreased the level of apoptosis
      at all doses as measured by caspase-3 activity and it prevented cells from
      undergoing radiation-induced size increase up to 1 Gy.

PMID- 22614097
TI  - Commentary: granins, secretory granule biogenesis, and transport.

PMID- 22614096
TI  - Adiposity to muscle ratio predicts incident physical limitation in a cohort of
      3,153 older adults--an alternative measurement of sarcopenia and sarcopenic
      obesity.
AB  - Conventionally, sarcopenia is defined by muscle mass and physical performance. We
      hypothesized that the disability caused by sarcopenia and sarcopenic obesity was
      related to the amount of adiposity or body weight bearing on a unit of muscle
      mass, or the adiposity to muscle ratio. We therefore examined whether this ratio
      could predict physical limitation by secondary analysis of the data in our
      previous study. We recruited 3,153 community-dwelling adults aged >65 years and
      their body composition was measured by dual-energy X-ray absorptiometry.
      Assessment of physical limitation was undertaken 4 years later. The relationship
      between baseline adiposity to muscle ratio and incident physical limitation was
      examined by logistic regression. In men, the adiposity to muscle ratios, namely
      total body fat to lower-limb muscle mass, total body fat to fat-free mass (FFM),
      and body weight to FFM, were predictive of physical limitation before and after
      adjustment for the covariates: age, Mini-mental Status Examination score,
      Geriatric Depression Scale score >8, and the diagnosis of chronic obstructive
      pulmonary disease, diabetes mellitus, hypertension, heart disease, and stroke
      (all p values < 0.001), when the total body fat to lower-limb muscle mass ratio
      was greater than or equal to 0.75. In women, throughout the entire range of that
      ratio, all three adiposity to muscle ratios were associated with physical
      limitation 4 years later both before and after adjustment for the same set of
      covariates (all p values < 0.05). Sarcopenia and sarcopenic obesity as measured
      by the body weight or adiposity bearing on a unit of muscle mass (the adiposity
      to muscle ratio) could predict incident or worsening physical limitation in older
      women across the entire range of the total body fat to lower-limb muscle mass
      ratio; and in older men when this ratio was equal to or greater than 0.75.

PMID- 22614098
TI  - Endolithic phototrophs in built and natural stone.
AB  - Lichens, algae and cyanobacteria have been detected growing endolithically in
      natural rock and in stone buildings in various countries of Australasia, Europe
      and Latin America. Previously these organisms had mainly been described in
      natural carbonaceous rocks in aquatic environments, with some reports in
      siliceous rocks, principally from extremophilic regions. Using various culture
      and microscopy methods, we have detected endoliths in siliceous stone, both
      natural and cut, in humid temperate and subtropical climates. Such endolithic
      growth leads to degradation of the stone structure, not only by mechanical means,
      but also by metabolites liberated by the cells. Using in vitro culture,
      transmission, optical and fluorescence microscopy, and confocal laser scanning
      microscopy, both coccoid and filamentous cyanobacteria and algae, including
      Cyanidiales, have been identified growing endolithically in the facades of
      historic buildings built from limestone, sandstone, granite, basalt and
      soapstone, as well as in some natural rocks. Numerically, the most abundant are
      small, single-celled, colonial cyanobacteria. These small phototrophs are
      difficult to detect by standard microscope techniques and some of these species
      have not been previously reported within stone.

PMID- 22614099
TI  - Enantioselective dynamic process reduction of alpha- and beta-tetralone and
      stereoinversion of resulting alcohols in a selected strain culture.
AB  - alpha-Tetralone and beta-tetralone were subjected to biotransformation by 14
      fungal strains. Enantiomeric purity of the products depended on the reaction
      time. 3-Day transformation of alpha-tetralone in Absidia cylindrospora culture
      gave S-(+)-1,2,3,4-tetrahydro-1-naftol of 92 % ee, whereas longer
      biotransformation time resulted in decrease of ee value. 3-Day transformation of
      beta-tetralone by the same strain gave predominantly S-(-)-1,2,3,4-tetrahydro-2
      naftol, whereas after 9 days of the reaction, the R-enantiomer with 85 % ee was
      isolated. Transformation of beta-tetralone by Chaetomium sp. KCh 6651 gave pure
      (S)-(-)-1,2,3,4-tetrahydro-2-naftol in high yield at the concentration of 1 g/l.
      In this process, a non-selective carbonyl reduction was observed, followed by a
      selective oxidation of the R-alcohol.

PMID- 22614100
TI  - Biochemical and microbial analysis of ovine rumen fluid incubated with 1,3,5
      trinitro-1,3,5-triazacyclohexane (RDX).
AB  - In this study, the rumen was assessed for its potential to detoxify RDX using
      molecular microbial ecology as well as analytical chemistry techniques. Results
      indicated significant loss (P < 0.05) of RDX in <8-h post incubation, and
      qualitative LC-MS/MS analysis showed evidence for the formation of 1-NO-RDX (M-O
      + HCOO) and methylenedinitramine metabolites. A total of 1106 16S rRNA-V3 clones
      were sequenced, and most sequences associated with either the phyla Bacteroidetes
      or Firmicutes. A LibCompare analysis for the RDX treatment showed an enrichment
      (P < 0.01) of the genus Prevotella. From these results, it can be concluded that
      the rumen is capable of detoxifying RDX, and the members of the genus Prevotella
      are linked to this detoxification.

PMID- 22614101
TI  - Critical evaluation of phosphate solubilizing pseudomonads isolated from a
      partially recultivated potash tailings pile.
AB  - Ten phosphate solubilizing pseudomonads isolated from a partially recultivated
      potash tailings pile in Germany were characterized and tested for their potential
      to assist in the ongoing recultivation process. Despite fertilization, the plants
      which are grown for recultivation show phosphate deficiency symptoms, and
      therefore the isolates are intended to be used as biofertilizer inoculants. On
      agar plates incubated at five different temperatures, some of the strains showed
      a temperature-dependent ability to solubilize tricalcium phosphate, while others
      performed the same at any given temperature. In liquid medium, the isolates
      solubilized between 271 and 730 MUg ml(-1) of phosphate from tricalcium
      phosphate. Both the weakest (designated S10) and the strongest solubilizing
      strain (S06) were further tested for their viability during solubilization. In an
      assay over the course of 1 week, both strains released their maximum amount of
      phosphate after 2-4 days. At that later point of time, however, viable cells of
      isolate S06 were no longer detectable, whereas the weaker strain S10 could be
      cultured after 1 week in broth. Taking all in vitro observations into account,
      the usability of the isolates as biofertilizers is critically discussed regarding
      both the in situ conditions on the tailings pile and the lowered viability due to
      the excess production of organic acids.

PMID- 22614102
TI  - [A 38-year-old patient with gastroenteritis and unusual liver lesions].
AB  - A 38-year-old female presented with symptoms of gastroenteritis including fatigue
      and epigastric pain. An abdominal ultrasound indicated on the basis of raised
      liver values showed multiple liver lesions. However, additional imaging using
      contrast-enhanced ultrasound (CEUS), computer tomography (CT) as well as a
      magnetic resonance tomography (MR) failed to clarify the diagnosis. A fine needle
      biopsy revealed the histological diagnosis of peliosis hepatis. After
      discontinuing oral contraceptive medication, follow-up showed a steady state with
      clinical well being for at least 24 months.Peliosis hepatis is a rare hepatic
      disorder involving "bloody cysts" in the liver. Aetiology and pathogenesis remain
      unclear, but medication or toxins as possible triggering factors are discussed.
      Different clinical courses have been reported, including total asymptomatic
      state, unspecific fatigue, epigastric pain, as well as fulminant cases with liver
      rupture and bleeding complications.

PMID- 22614104
TI  - Intervention in gastrointestinal stromal tumour with a high risk of malignancy
      and associated with thalassaemia minor.
AB  - This study reports on a 65-year-old female patient with controlled comorbidity,
      who was diagnosed with gastrointestinal stromal tumours following regular
      monitoring of renal cysts. After the surgical treatment, coadjuvant treatment
      with imatinib was initiated. After a few months, the patient complained of angor
      and asthenia and the diagnosis of anaemic syndrome was made on the basis of blood
      test results. We studied the causes of the anaemia (maturation factors and other
      causes of secondary anaemia) and it led to the diagnosis of vitamin B12
      deficiency. Treatment with vitamin B12 supplementation was initiated. With the
      correction of the vitamin levels with supplementation, the symptoms improved.
      Thalassaemia led to the misdiagnosis of vitamin B12 deficiency because of the
      lower mean corpuscular volume levels.

PMID- 22614103
TI  - Difference in serum complement component C4a levels between hepatitis C virus
      carriers with persistently normal alanine aminotransferase levels or chronic
      hepatitis C.
AB  - Certain hepatitis C virus (HCV) carriers exhibit persistently normal alanine
      aminotransferase (ALT) levels (PNALT) (<= 30 IU/l) accompanied by normal platelet
      counts (>= 15 x 10(4)/ul); these individuals show milder disease activity and
      slower progression to cirrhosis. This study aimed to elucidate the
      characteristics of HCV carriers with PNALT using serum proteomics. The first
      group of subjects, who underwent clinical evaluation in the hospital, consisted
      of 19 HCV carriers with PNALT (PNALT-1) and 20 chronic hepatitis C (CHC-1)
      patients. The second group of subjects was part of a cohort study on the natural
      history of liver disease, and included 37 PNALT (PNALT-2) and 30 CHC (CHC-2)
      patients. Affinity bead-purified serum protein was subjected to matrix-assisted
      laser desorption ionization time-of-flight mass spectrometry analysis. Serum
      proteomics showed that 6 protein peaks with mass-to-charge ratios ranging from
      1,000 to 3,000 differed significantly between the PNALT-1 and CHC-1 groups. Among
      these peaks, a 1738-m/z peak protein was identified as a fragment of complement
      component 4 (C4) and correlated significantly with serum C4a concentrations as
      determined by enzyme immunoassay. Serum C4a levels were also significantly higher
      in the PNALT-2 group compared to the CHC-2 group and healthy volunteers.
      Furthermore, in the PNALT-2 group, serum C4a levels negatively correlated with
      transaminase levels, but not with other biochemical tests, HCV core antigen
      levels, peripheral blood cell counts or serum hepatic fibrosis markers. This
      study indicates that host factors such as C4a not only differ between HCV
      carriers with PNALT and CHC, but that proteomic approaches could also contribute
      to the elucidation of factors in PNALT as more differences are discovered.

PMID- 22614105
TI  - A new chiral 2-(ethylthio)-thiazolone analogue shows strong antitumor activities
      by inducing cancer cell apoptosis and inhibiting angiogenesis.
AB  - Our initial study showed the potent cytotoxic effects of a series of new chiral 2
      (ethylthio)-thiazolone analogues we synthesized. In the present study, we used
      computer prediction and found that nitro functionality and the modification of
      substituents R could further improve their activities in the presence of the
      nitro group. Compound 1s with nitro, naphthyl, ethyl groups, and a chiral center
      was predicted to be the most effective. We showed that compound 1s could inhibit
      the growth of five different cancer cell lines in a time-dependent and dose
      dependent manner. 1s could induce Hela cell apoptosis by activating the
      mitochondria apoptotic pathway. In addition, 1s could inhibit the proliferation,
      migration, tuber formation, and adhesion of human umbilical vein endothelial
      cells, suggesting its antiangiogenesis effects. Furthermore, we confirmed the in
      vivo antitumor effects of 1s on sarcoma S-180-bearing mice. Taken together,
      chiral 2-(ethylthio)-thiazolone analogue 1s is a promising compound for further
      anticancer drug development.

PMID- 22614106
TI  - Superior cytotoxicity and DNA cross-link induction by oxaliplatin versus
      cisplatin at lower cellular uptake in colorectal cancer cell lines.
AB  - Platinum-based chemotherapeutic agents are considered among the most potent
      anticancer drugs used in the treatment of human tumors. Cisplatin is efficient in
      the treatment of testicular, ovarian, bladder, and head and neck carcinomas,
      although its use is limited by severe nephrotoxicity and ototoxicity and
      resistance. Oxaliplatin has consistently exerted antitumor activity in colon,
      ovarian, and lung cancers and shown less toxicity than its analogue. Given that
      most of the literature data are contradictory with respect to the cytotoxicity of
      these drugs and DNA adduct formation, the present study aimed to determine some
      of the potential underlying mechanisms in view of their cellular uptakes. We
      evaluated the cytotoxicity, DNA cross-link formation, and cellular uptake of
      cisplatin and oxaliplatin in Colo320, HT-29, and Caco-2 colorectal adenocarcinoma
      cell lines. Our results showed higher cytotoxicity of oxaliplatin in Colo320
      (P<0.05) and HT-29 cell lines and of cisplatin in Caco-2 (P<0.05). Oxaliplatin
      induced more DNA cross-links than cisplatin in a dose-dependent manner in Colo320
      cells (P<0.0001); in HT-29 and Caco-2 cells, the induction of DNA damage was not
      dose dependent. Multiple accumulation of cisplatin versus oxaliplatin occurred in
      all the cell types, doses, and time points we tested. Oxaliplatin showed more
      potent biological activities versus cisplatin in terms of a significantly lower
      cellular uptake. In addition to their analogous mechanisms of action, these drugs
      might activate different signal transduction pathways, ultimately leading to
      apoptotic DNA fragmentation and cell death. DNA damage, although perhaps the most
      important, represents only one aspect of the multiple effects of platinum drugs.

PMID- 22614107
TI  - Zafirlukast antagonizes ATP-binding cassette subfamily G member 2-mediated
      multidrug resistance.
AB  - ATP-binding cassette (ABC) transporters are present in the majority of human
      tumors and are involved in multidrug resistance (MDR). Therefore, compounds that
      inhibit the function of ABC transporters may improve the efficacy of anticancer
      agents. Previous research has shown that zafirlukast is a reversal drug for
      multidrug resistance protein (MRP) 1-mediated MDR. In the present study, we
      assessed whether zafirlukast could be a reversal agent for other ABC transporter
      mediated MDR. Using the MTT assay, we found that zafirlukast enhanced the
      cytotoxicity of several anticancer drugs that are substrates of breast cancer
      resistance proteins (BCRP/ABCG2), including mitoxantrone and SN-38. Furthermore,
      zafirlukast could partially reverse P-glycoprotein-mediated (P-gp/ABCB1) and MRP7
      (ABCC10)-mediated MDR at nontoxic doses. Studies on [(3)H]-mitoxantrone
      accumulation and efflux have shown that zafirlukast increases the intracellular
      accumulation of [(3)H]-mitoxantrone by directly inhibiting ABCG2-mediated drug
      efflux. Western blot analysis indicated that zafirlukast did not alter the
      expression of ABCG2. In addition, a docking model predicted the binding
      conformation of zafirlukast within the transmembrane region of homology-modeled
      human ABCG2. Our findings suggest a possible strategy to potentially enhance the
      activity of anticancer drugs using a clinically approved drug with known side
      effects and drug-drug interactions.

PMID- 22614109
TI  - Screening celiac disease in at-risk groups: effect of diagnosis on perceived
      health of children and their families.

PMID- 22614108
TI  - Pancreatic insufficiency is not a prevalent problem in Alagille syndrome.
AB  - Alagille syndrome (ALGS) is an inherited multisystem disorder in which pancreatic
      insufficiency (PI) has been regarded a minor but important clinical
      manifestation. As part of a multicenter prospective study, 42 patients with ALGS
      underwent fecal elastase (FE) measurement to screen for exocrine PI. FE
      measurements were normal (>200  MUg/g) in 40 (95%) and indeterminate (100-200 
      MUg/g) in 2 (5%). As FE is the most reliable screen for PI, these data suggest
      that PI is not a prevalent problem in ALGS.

PMID- 22614110
TI  - Burden of illness in screen-detected children with celiac disease and their
      families.
AB  - OBJECTIVES: Because of a variable clinical picture, most children with celiac
      disease remain unrecognized without active serologic screening. Because, however,
      many patients are asymptomatic, the justification for screening remains unclear.
      We assessed health and well-being and the effect of a 1-year gluten-free diet in
      a nationwide cohort of children with celiac disease detected by screening in at
      risk groups. METHODS: A total of 222 newly detected children received a validated
      questionnaire covering aspects of the burden caused by the undiagnosed celiac
      disease. After 1 year, adherence to the diet and difficulties attending this,
      attitudes toward and effects of disease and diet on daily life, and parents'
      satisfaction with the diagnosis were inquired about. The children's health and
      parents' concern for it were asked about at diagnosis and on treatment. The
      outcomes of screen-detected children were compared with those of children
      diagnosed on the basis of clinical symptoms. RESULTS: Forty-three screen-detected
      and 88 symptom-detected children responded. Also, 65% of the screen-detected
      patients experienced symptoms; these, however, being less troublesome and of
      shorter duration than in symptom-detected subjects. There were no differences
      between the groups in dietary adherence (71% vs 84% strict diet), management of
      the diet (80% vs 80%), alleviation of symptoms (78% vs 86%), and improvement in
      daily life (73% vs 69%), or in satisfaction with the diagnosis (93% vs 88%).
      Improved health and reduced parental concern were observed in both groups.
      CONCLUSIONS: Screen-detected children with celiac disease can attain satisfactory
      dietary adherence and benefit from treatment similarly to symptom-detected
      patients. The results support intensified screening for celiac disease in at-risk
      children.

PMID- 22614111
TI  - Treatment with pamidronate for osteoporosis complicating long-term intestinal
      failure.
AB  - Long-term home parenteral nutrition (PN) is a potential risk for developing
      osteoporosis. Various attempts have been made to treat bone disease both by
      modifying the composition of PN and by administering hormones, such as
      calcitonin, parathyroid hormone, and sexual hormones. Bisphosphonates are
      recognized as a medication useful for the treatment of several bone disorders
      associated with excessive reabsorption. Nevertheless, there have been no
      paediatric studies on bisphosphonates use for intestinal failure-associated bone
      disease. Our study includes 6 paediatric patients receiving extremely long-term
      home PN (at least 3 years) who showed radiological and clinical signs of
      osteoporosis. Diagnosis of bone disease was made after a median period of 127.5
      PN months. Treatment consisted in 2 cycles of intravenous pamidronate, 30 mg/m
      once per month for 6 months consecutively. They all showed a significant
      improvement in bone mineral density, evaluated after 6 and 12 months of
      pamidronate treatment. In our sample anthropometrical variables (weight, height,
      and body mass index) are not related with the z-score trend. Our patients had
      normal levels of calcium, phosphorus, and vitamin D, and proper nutrient intake.
      At the last follow-up, dual-energy x-ray absorptiometry scan showed that no
      patients had a z-score lower than -2.5; moreover, nobody developed bone fractures
      during the 108-month follow-up. The patients did not have any prominent adverse
      effect. Finally, in our experience, pamidronate is effective for improving bone
      mineral density and safe in patients with intestinal failure-associated bone
      disease.

PMID- 22614112
TI  - Serial evaluation of children with ALF with advanced MRI, serum proinflammatory
      cytokines, thiamine, and cognition assessment.
AB  - OBJECTIVES: This prospective, sequential study was done to understand changes in
      cerebral edema (CE) on magnetic resonance imaging and magnetic resonance
      spectroscopy, liver functions, and neurocognitive testing (NCT) in children with
      acute liver failure (ALF). METHODS: A total of 11 ALF and 8 healthy controls were
      evaluated with advanced magnetic resonance (MR) imaging, blood proinflammatory
      cytokines (PCs), thiamine levels, liver functions, and NCT. Reevaluation was done
      at 43.5 +/- 26.9 days (first follow-up, n = 8) and 157.3 +/- 52.3 days (second
      follow-up, n = 6) after discharge. RESULTS: At diagnosis, patients with ALF had
      vasogenic and cytotoxic CE, raised brain glutamine (23.2 +/- 3.4 vs. 15.3 +/-
      2.7), and serum PCs (tumor necrosis factor [TNF]-alpha 40.1 +/- 8.9 vs. 7.2 +/-
      2.7  pg/mL, interleukin [IL]-6 29.2 +/- 14.4 vs. 4.7 +/- 1.2  pg/mL). The
      mammillary bodies (MBs) were smaller, and brain choline (1.9 +/- 0.36 vs. 2.6 +/-
      0.6) and blood thiamine (55.2 +/- 6.7 vs. 81.8 +/- 10.2  nmol/L) were lower than
      controls. At first follow-up, the brain glutamine and CE recovered. Brain choline
      and MBs volume showed improvement and thiamine levels normalized. Significant
      reduction in TNF-alpha and IL-6 was seen. The patients performed poorly on NCT,
      which normalized at second follow-up. Liver biochemistry and thiamine levels were
      normal and TNF-alpha and IL-6 showed further reduction at second follow-up.
      CONCLUSIONS: Patients with ALF have CE contributed by raised brain glutamine and
      PCs. MBs are small because of thiamine deficiency and show recovery in follow-up.
      CE and brain glutamine recover earlier than normalization of NCT and liver
      functions. Persistence of raised cytokines up to 6 months after insult suggests
      possible contribution from liver regeneration.

PMID- 22614113
TI  - Effect of bowel cleansing for colonoscopy on fecal calprotectin levels in
      pediatric patients.
AB  - The recent development of easily applicable fecal surrogate markers of intestinal
      inflammation, such as fecal calprotectin (FC), has provided a new means for
      objectively assessing disease activity in patients with chronic inflammatory
      bowel disease. Because the use of these markers is about to emerge, it is
      important to be aware of the possible limitations of measurements. We assessed
      levels of FC during bowel cleansing. In patients with high FC levels at baseline,
      the values measured during bowel cleansing varied considerably, remaining high or
      even returning to normal. Thus, stool sampling for FC assessment is not
      recommended during bowel preparation for colonoscopy.

PMID- 22614114
TI  - Endoscopic surveillance and primary prophylaxis sclerotherapy of esophageal
      varices in biliary atresia.
AB  - OBJECTIVES: Evidence-based recommendations on endoscopic screening and
      prophylactic treatment of esophageal varices in patients with biliary atresia
      (BA) are scarce. We assessed the efficiency of endoscopic surveillance and risk
      factors of esophageal varices and associated upper gastrointestinal bleeding.
      METHODS: A total of 47 consecutive children with BA and portoenterostomy
      underwent yearly endoscopies and prophylactic injection sclerotherapy of
      esophageal varices between 1987 and 2009. The median follow-up was 1.7 years
      (range 0.5-18.9) and overall 2-year survival 71%. Disease characteristics,
      clearance of jaundice, laboratory tests reflecting liver function and
      hypersplenism, as well as sonographic signs of portal hypertension were related
      to endoscopic findings and bleeding episodes. RESULTS: Grade 2 to 3 varices
      developed with similar frequency after failed (18/28, 64%) and successful
      portoenterostomy (10/19, 53%) in 28 patients. Following failed portoenterostomy,
      esophageal varices were encountered significantly earlier (8 [4-23] vs. 19 [4
      165] months, P = 0.004), and they reappeared after eradication more often (16/16
      vs. 4/10, P = 0.001). Varices bled only after failed portoenterostomy (13/28 vs.
      0/19, P < 0.001). Increased serum bilirubin concentration >40 MUmol/L at 3 months
      after portoenterostomy was a risk factor of upper gastrointestinal bleeding (odds
      ratio [OR] 17, 95% confidence interval [CI] 1.7-175, P = 0.017). CONCLUSIONS: In
      future studies as well as clinical surveillance of BA patients' varices,
      successful and failed portoenterostomy patients should be approached as separate
      groups with divergent prognoses. After failed portoenterostomy, surveillance
      should start early, for example, at 6 months.

PMID- 22614115
TI  - Surface-enhanced Raman spectroscopic study of p-aminothiophenol.
AB  - p-aminothiophenol (PATP) is an important molecule for surface-enhanced Raman
      spectroscopy (SERS). It can strongly interact with metallic SERS substrates and
      produce very strong SERS signals. It is a molecule that has often been used for
      mechanistic studies of the SERS mechanism as the photon-driven charge transfer
      (CT) mechanism is believed to be present for this molecule. Recently, a hot
      debate over the SERS behavior of PATP was triggered by our finding that PATP can
      be oxidatively transformed into 4,4'-dimercaptoazobenzene (DMAB), which gives a
      SERS spectra of so-called "b2 modes". In this perspective, we will give a general
      overview of the SERS mechanism and the current status of SERS studies on PATP. We
      will then demonstrate with our experimental and theoretical evidence that it is
      DMAB which contributes to the characteristic SERS behavior in the SERS spectra of
      PATP and analyze some important experimental phenomena in the framework of the
      surface reaction instead of the contribution "b2 modes". We will then point out
      the existing challenges of the present system. A clear understanding of the
      reaction mechanism for nitrobenzene or aromatic benzene will be important to not
      only understand the SERS mechanism but to also provide an economic way of
      producing azo dyes with a very high selectivity and conversion rate. 

PMID- 22614116
TI  - The relationship of Akathisia with treatment emergent suicidality among patients
      with first-episode schizophrenia treated with haloperidol or risperidone.
AB  - Akathisia as well as younger age, early illness onset and discharge are important
      risk factors for suicidality in patients with first-episode schizophrenia. The
      aim of the present study was to analyze on a single case basis the relationship
      between a sudden increase in suicidality, anxiety symptoms, medication dosing and
      clinician- and patient-rated akathisia. A small subsample of patients
      demonstrated a positive relationship between suicidality and akathisia scores
      within the titration period of the study medication.

PMID- 22614117
TI  - Interleukin 11 regulates endometrial cancer cell adhesion and migration via
      STAT3.
AB  - Endometrial carcinoma is the most common gynaecological malignancy. There is
      however a lack of curative therapies, especially for patients diagnosed with late
      stage, recurrent or aggressive disease, who have a poor prognosis. Interleukin
      (IL) 11 is a pleiotropic cytokine that has a role in a number of cancers
      including colon and breast cancer. IL11 was recently found to be upregulated in
      endometrial cancers, however the function of IL11 in endometrial cancer is not
      known. This study aimed to determine the effects of IL11 on endometrial cancer
      cell proliferation, adhesion and migration. Three endometrial cancer cell lines,
      Ishikawa, HEC-1A and AN3CA (derived from endometrial cancers grade I, II and III,
      respectively), were used to determine the effect of IL11 on endometrial cancer
      cell function. Cell proliferation and viability were assessed by BrdU and Wst-1
      assays. Cell adhesion to the extracellular matrix proteins fibronectin, collagen
      I and IV, vitronectin and laminin was assessed. Modified boyden chambers were
      utilized to access IL11 action on migration and invasion, respectively. The
      specific effect of IL11 action on these processes was determined using a unique
      IL11 inhibitor. IL11 phosphorylated (p)-STAT3 protein abundance in all 3 cell
      lines but had no effect on pERK and pAKT abundance. Similarly, IL11 had no effect
      on cell proliferation and viability but increased adhesion of ANC3A cells to
      fibronectin while having no effect on the other extracellular matrix proteins.
      IL11 did not alter the adhesive properties of the Ishikawa and HEC-1A cells. In
      the AN3CA cells, IL11 treatment resulted in a 50% increase in migration and co
      treatment with the specific IL11 inhibitor or a STAT3 inhibitor abolished the
      effect. This study shows a role for IL11 in endometrial cancer and suggests IL11
      may be involved in endometrial cancer development and thus may be useful as a
      therapeutic target.

PMID- 22614118
TI  - The transcription levels of ABCA1, ABCG1 and SR-BI are negatively associated with
      plasma CRP in Chinese populations with various risk factors for atherosclerosis.
AB  - ATP binding cassette transporters (ABCA1, ABCG1) and scavenger receptor class B
      type I (SR-BI) are the three most important cellular cholesterol transporters
      that may prevent atherogenesis. The aim of this study was to investigate whether
      they were altered in Chinese populations with various risk factors for
      atherosclerosis and their potential associations with C-reactive protein (CRP).
      Healthy female controls (n = 30) and populations with various risk factors for
      atherosclerosis, such as type 2 diabetes (n = 17), hypertension (n = 12),
      overweight/obesity (n = 10), incipient nephropathy (n = 10), postmenopausal women
      (n = 9), male (n = 19), ageing male (n = 22), or smoking (n = 16), were
      recruited. ABCA1, ABCG1 and SR-BI mRNA levels in peripheral monocytes was
      determined. ABCG1 was decreased in all the risk populations except ageing. ABCA1
      was decreased in all the risk populations except diabetes and male. SR-BI was
      decreased in those with overweight/obesity and incipient nephropathy. Circulating
      CRP was increased almost in all the risk populations except in males. The levels
      of ABCA1, ABCG1 and SR-BI were reduced in those with subclinically high CRP, and
      negatively associated with CRP level. These data indicates that ABCA1, ABCG1, and
      SR-BI are reduced in various populations under subclinically inflammatory
      conditions, which may potentially lead to impairing reverse cholesterol transport
      and developing atherosclerosis.

PMID- 22614120
TI  - Polystyrene-supported TBD catalyzed ring-opening of N-tosylaziridines with
      silylated nucleophiles.
AB  - Polystyrene-supported TBD (PS-TBD) catalyzes the ring-opening of N
      tosylaziridines with silylated nucleophiles to give the corresponding products in
      high yields. PS-TBD was easily recovered and reused without significant loss of
      catalytic activity.

PMID- 22614119
TI  - Sulfated derivative of 20(S)-ginsenoside Rh2 inhibits inflammatory cytokines
      through MAPKs and NF-kappa B pathways in LPS-induced RAW264.7 macrophages.
AB  - In the previous study, we found that sulfated derivative B2 of ginsenoside Rh2
      (Rh2-B2) has greater anti-inflammatory effects than 20(S)-ginsenoside Rh2.
      However, the anti-inflammatory mechanism of Rh2-B2 remains unclear. We therefore
      assessed the effects of Rh2-B2 on inflammatory cytokines in lipopolysaccharide
      (LPS)-stimulated RAW264.7 macrophages. We found that Rh2-B2 (1-5 mg/L)
      significantly inhibited tumor necrosis factor alpha, interleukin (IL)-6, IL
      1beta, and increased IL-10 production from protein and mRNA levels. Furthermore,
      Rh2-B2 significantly inhibited the phosphorylation of p38 and c-Jun N-terminal
      kinase as well as decreased p65 nuclear factor kappa-light-chain-enhancer of
      activated B cells (NF-kappaB) translocation into the nucleus by nuclear factor of
      kappa light polypeptide gene enhancer in B-cells inhibitor, alpha degradation.
      The present results indicate that Rh2-B2 inhibits the production of inflammatory
      cytokines induced by LPS through blocking mitogen-activated protein kinases and
      NF-kappaB signaling pathways.

PMID- 22614122
TI  - Summary of the IADR Cariology Research Group Symposium, Barcelona, Spain, July
      2010: new directions in cariology research.
AB  - Caries remains the most prevalent noncontagious biofilm-mediated disease in
      humans. It is clear that the current approaches to decrease the prevalence of
      caries in human populations, including water fluoridation and school-based
      programs, are not enough to protect everyone. The scientific community has
      suggested the need for innovative work in a number of areas in cariology,
      encompassing disease etiology, epidemiology, definition, prevention, and
      treatment. In this symposium, two of these areas, dealing specifically with
      etiological aspects of caries were discussed: (1) systematic research on caries
      risk assessment using population-based cohort techniques, and (2) genetic studies
      to identify genes and genetic markers of diagnostic, prognostic, and therapeutic
      value. This paper summarizes these presentations.

PMID- 22614121
TI  - Evaluation of intrapartum antibiotic prophylaxis for the prevention of early
      onset group B streptococcal infection.
AB  - We retrospectively assessed the medical records of pregnant women who delivered
      at Asahikawa Kosei Hospital during a period of 3 years between January 2009 and
      December 2011 and their neonates. Our prophylactic measures against group B
      Streptococcus (GBS) infection are based on the Japanese guidelines. More
      specifically, we performed screening by examining bacterial cultures of vaginal
      perianal swabs from pregnant women between gestational weeks 33 and 37. Then,
      sulbactam/ampicillin (SBT/ABPC) was given at a dose of 1.5 g through a drip
      intravenous infusion at delivery if pregnant women were screened positive for
      GBS. For neonates born to GBS carrier women, bacterial cultures of pharyngeal
      swabs, vernix caseosa, stool, and gastric juice were performed at birth. There
      were 2,399 deliveries and 2,499 births at our hospital. In 169 of the deliveries
      (175 of the births), GBS was isolated from specimens obtained from gestational
      weeks 33-37. According to delivery mode, there were 42 cases of cesarean section
      (45 births) and 127 cases of vaginal delivery (130 births). The GBS-positive
      neonates accounted for 4.1 % of all deliveries in pregnant women who tested
      positive for GBS at gestational weeks 33-37. In neonates born by vaginal
      delivery, the GBS-positive rate was 5.5 %. Of the 2,499 neonates born at our
      hospital during a period of 3 years, early-onset GBS infection occurred in 1
      neonate. The incidence of early-onset GBS infection was 0.40 per 1,000 live
      births. From 1997 to 2001 (routine GBS screening of mothers was not performed),
      there were 2,097 deliveries and 2,166 births. Early-onset GBS infection occurred
      in 1 neonate during this period; thus, the incidence of early-onset GBS infection
      was 0.46 per 1,000 live births. There were no significant differences in the two
      periods. The present prophylactic measures such as screening of maternal GBS
      carriers and intrapartum antibiotic administration are inadequate to decrease the
      occurrence of early-onset GBS infection.

PMID- 22614123
TI  - PI3K/Akt signaling pathway-induced heme oxygenase-1 upregulation mediates the
      adaptive cytoprotection of hydrogen peroxide preconditioning against oxidative
      injury in PC12 cells.
AB  - Both the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and heme oxygenase-1
      (HO-1) create a survival signal against oxidative stress-induced injuries.
      Although we have demonstrated that hydrogen peroxide (H2O2) preconditioning
      confers adaptive cytoprotection against oxidative stress-induced injury in PC12
      cells, it remains unknown whether these defense systems are involved in the
      protective effect of H2O2 preconditioning. In the current study, PC12 cells were
      preconditioned with 100 uM H2O2 for 90 min, followed by 24 h recovery and
      subsequent exposure to 300 uM H2O2 for further 12 h. The findings showed that
      preconditioning with 100 uM H2O2 upregulated HO-1 expression. Zinc protoporphyrin
      IX (ZnPP), a selective inhibitor of HO-1, at a concentration of 15 uM,
      significantly attenuated H2O2 preconditioning-elicited cytotoxicity, apoptosis,
      oxidative stress and mitochondrial membrane potential (DeltaPsim) loss in PC12
      cells. In addition, H2O2 preconditioning enhanced phosphorylation of Akt.
      Treatment with 25 uM LY294002, a selective inhibitor of PI3K, for 20 min before
      H2O2 preconditioning blocked not only H2O2 preconditioning-induced HO-1
      induction, but also the protective effect of H2O2 preconditioning against
      cytotoxicity. The present study provides novel evidence for the effect of
      preconditioning with H2O2 on the induction of HO-1, which contributes to the
      adaptive cytoprotection of H2O2 preconditioning against oxidative stress-induced
      cellular injury via a PI3K/Akt-dependent mechanism in PC12 cells.

PMID- 22614124
TI  - Control of human hematopoietic stem/progenitor cell migration by the
      extracellular matrix protein Slit3.
AB  - Patients whose hematopoietic system is compromised by chemo- and/or radiotherapy
      require transplantation of hematopoietic stem and progenitor cells (HSPCs) to
      restore hematopoiesis. Successful homing of transplanted HSPCs to the bone marrow
      (BM) largely depends on their migratory potential, which is critically regulated
      by the chemokine CXCL12. In this study, we have investigated the expression and
      function of Slit proteins and their corresponding Roundabout (Robo) receptors in
      human HSPC migration. Slit proteins are extracellular matrix proteins that can
      modulate the (chemoattractant-induced) migration of mature leukocytes. We show
      that mRNAs for all Slits (Slit1-3) are expressed in primary BM stroma and BM
      derived endothelial and stromal cell lines, but not in CD34+ HSPCs. Human CD34+
      HSPCs expressed mRNAs for all Robos (Robo1-4), but only the Robo1 protein was
      detected on their cell surface. Functionally, Slit3 treatment increased the in
      vivo homing efficiency of CD34+ HSPCs to the BM in NOD/SCID mice, whereas Slit3
      exposed HSPC migration in vitro was inhibited. These effects do not appear to
      result from modulated CXCL12 responsiveness as CXCR4 expression, CXCL12-induced
      actin polymerization or the basal and CXCL12-induced adhesion to fibronectin or
      BM-derived endothelial cells of CD34+ HSPC were not altered by Slit3 exposure.
      However, we show that Slit3 rapidly reduced the levels of active RhoA in HL60
      cells and primary CD34+ HSPC, directly affecting a pathway involved in actin
      cytoskeleton remodeling and HSPC migration. Together, our results support a role
      for Slit3 in human HSPC migration in vitro and homing in vivo and might
      contribute to the design of future approaches aimed at improving transplantation
      efficiency of human CD34+ HSPCs.

PMID- 22614125
TI  - Involvement of matrix metalloproteinase-2 in the development of renal
      interstitial fibrosis in mouse obstructive nephropathy.
AB  - Renal fibrosis is a common finding in progressive renal diseases. Matrix
      metalloproteinases (MMPs) are involved in epithelial-to-mesenchymal transition
      (EMT). We investigated the role of MMP-2 and the effect of inhibition of MMPs on
      the development of renal fibrosis. Renal fibrosis was induced in MMP-2 wild-type
      (MMP-2+/+) mice by unilateral ureteral obstruction (UUO). Renal histopathology,
      EMT-associated molecules, and activity of MMP-2 and MMP-9 were examined during
      the development of interstitial fibrosis. UUO-renal fibrosis was also induced in
      MMP-2 deficient (MMP-2-/-) and MMP-2+/+ mice treated with minocycline (inhibitor
      of MMPs). In MMP-2+/+ mice, MMP-2 and MMP-9 were expressed in damaged tubules,
      and their activities increased in a time-dependent manner after UUO. Interstitial
      fibrosis was noted at day 14, with deposition of types III and I collagens and
      expression of markers of mesenchymal cells (S100A4, vimentin, alpha-smooth muscle
      actin, and heat shock protein-47) in damaged tubular epithelial cells, together
      with F4/80+ macrophage infiltration. Fibrotic kidneys expressed EMT-associated
      molecules (ILK, TGF-beta1, Smad, Wnt, beta-catenin, and Snail). In contrast, the
      kidneys of MMP-2-/- mice and minocycline-treated MMP-2+/+ mice showed
      amelioration of renal fibrosis with reduced expression of markers of mesenchymal
      cells in tubular epithelial cells, inhibition of upregulated EMT-associated
      molecules, and suppression of macrophage infiltration. The results suggested that
      MMP-2 have a pathogenic role in renal interstitial fibrosis, possibly through the
      induction of EMT and macrophage infiltration. Inhibition of MMPs may be
      beneficial therapeutically in renal fibrosis.

PMID- 22614126
TI  - Continuous positive airway pressure requirements in patients with tetraplegia and
      obstructive sleep apnoea.
AB  - STUDY DESIGN: Clinic-based retrospective case-control study. OBJECTIVES: To
      compare continuous positive airway pressure (CPAP) requirements between patients
      with tetraplegia and able-bodied patients with obstructive sleep apnoea (OSA).
      SETTING: Melbourne, Australia. METHODS: Diagnostic and CPAP titration
      polysomnograms of 219 able-bodied, and 25 patients with tetraplegia and OSA were
      compared for apnoea hypopnoea index (AHI) and CPAP levels required to effectively
      treat OSA. Demographics and body mass index (BMI) were obtained for each patient.
      ASIA score and injury date were obtained for patients with tetraplegia. RESULTS:
      There was no significant difference in AHI (P=0.102) between the two groups;
      however, able-bodied patients were significantly older (P=0.003), required
      significantly higher levels of CPAP to control their OSA (P<0.001) and had higher
      BMIs (P=0.009) than patients with tetraplegia. In the tetraplegia group, there
      was no significant correlation between AHI and effective CPAP (r=0.022, P=0.92)
      or between AHI and BMI (r=-0.196, P=0.35). There was a significant correlation
      between effective CPAP and BMI (r=0.411, P=0.041). Among able-bodied patients,
      over two-thirds (68.8%) required 10-16 cm H(2)0 to control their OSA and nearly
      one-third required over 16 cm H(2)0. In contrast, over two-thirds (68.8%) in the
      tetraplegia group required less than 10 cm H(2)0 of CPAP to control their OSA.
      CONCLUSION: This retrospective study suggests that OSA patients with tetraplegia
      require significantly less CPAP to treat their OSA at any given AHI than those
      who are able-bodied. This suggests that additional unknown factors may contribute
      to the high prevalence of OSA in tetraplegia.

PMID- 22614128
TI  - Synthesis of the anti-trypanosomal agent (+/-)-hydroxyanthecotulide by Cr(ii)
      catalysed allylation and Meyer-Schuster rearrangement.
AB  - The first synthesis of the bioactive sesquiterpene lactone hydroxyanthecotulide
      is achieved in 7 steps, involving a stereocontrolled Cr(ii)-catalysed reaction of
      3-(bromomethyl)furan-2(5H)-one with enynal 9 and a mild Au(i)-catalysed Meyer
      Schuster rearrangement.

PMID- 22614127
TI  - [Rehabilitation management system of the German Social Accident Insurance.
      Initial medical experiences].
AB  - To improve outcome quality of rehabilitation, the German Social Accident
      Insurance implemented a rehabilitation management system. A rehabilitation
      manager operates as active supervisor of the rehabilitation process of severely
      injured persons beginning from the time when the accident happened. The sequence
      is recorded on a rehabilitation schedule by the physician, rehabilitation manager
      and patient together. The concept has not yet been fully accepted by all
      insurers. Furthermore there is no uniform approach in compiling the
      rehabilitation schedule which can lead to delays in the process and insecurity of
      patients. In the following article these aspects are illustrated and improvement
      suggestions are highlighted.

PMID- 22614129
TI  - Fetal cardiac function: technical considerations and potential research and
      clinical applications.
AB  - Fetal echocardiography was initially used to detect structural anomalies but has
      more recently also been proposed to assess fetal cardiac function. This review
      summarizes technical issues and limitations in fetal cardiac function evaluation,
      as well as its potential research and clinical applications. Functional
      echocardiography has been demonstrated to select high-risk populations and to be
      associated with outcome in several fetal conditions including intrauterine growth
      restriction, twin-to-twin transfusion syndrome, maternal diabetes, and congenital
      diaphragmatic hernia. Fetal heart evaluation is challenging due to the smallness
      and high heart rate of the fetus and restricted access to the fetus far from the
      transducer. Due to these limitations and differences in cardiac function which
      are related to fetal maturation, cardiovascular parameters should be validated in
      the fetus and used with caution. Despite these precautions, in expert hands and
      with appropriate ultrasound equipment, evaluation of cardiac function is feasible
      in most fetuses. Functional fetal echocardiography is a promising tool that may
      soon be incorporated into clinical practice. Research is warranted to further
      refine the contribution of fetal cardiac assessment to the diagnosis, monitoring,
      or prediction of outcomes in various fetal conditions.

PMID- 22614131
TI  - Obesity hypoventilation syndrome: a review of epidemiology, pathophysiology, and
      perioperative considerations.
AB  - Obesity hypoventilation syndrome (OHS) is defined by the triad of obesity,
      daytime hypoventilation, and sleep-disordered breathing without an alternative
      neuromuscular, mechanical, or metabolic cause of hypoventilation. It is a disease
      entity distinct from simple obesity and obstructive sleep apnea. OHS is often
      undiagnosed but its prevalence is estimated to be 10-20% in obese patients with
      obstructive sleep apnea and 0.15-0.3% in the general adult population. Compared
      with eucapnic obese patients, those with OHS present with severe upper airway
      obstruction, restrictive chest physiology, blunted central respiratory drive,
      pulmonary hypertension, and increased mortality. The mainstay of therapy is
      noninvasive positive airway pressure. Currently, information regarding OHS is
      extremely limited in the anesthesiology literature. This review will examine the
      epidemiology, pathophysiology, clinical characteristics, screening, and treatment
      of OHS. Perioperative management of OHS will be discussed last.

PMID- 22614130
TI  - The path from skin to brain: generation of functional neurons from fibroblasts.
AB  - Cell fate reprogramming makes possible the generation of new cell types from
      healthy adult cells to replace those lost or damaged in disease. Additionally,
      reprogramming patient cells into specific cell types allows for drug screening
      and the development of new therapeutic tools. Generation of new neurons is of
      particular interest because of the potential to treat diseases of the nervous
      system, such as neurodegenerative disorders and spinal cord injuries, with cell
      replacement therapy. Recent advances in cell fate reprogramming have led to the
      development of novel methods for the direct conversion of fibroblasts into
      neurons and neural stem cells. This review will highlight the advantages of these
      new methods over neuronal induction from embryonic stem cells and induced
      pluripotent stem cells, as well as outline the limitations and the potential for
      future applications.

PMID- 22614132
TI  - Hemodynamic and hormonal stress responses to endotracheal tube and ProSeal
      Laryngeal Mask AirwayTM for laparoscopic gastric banding.
AB  - BACKGROUND: The stress responses from tracheal intubation are potentially
      dangerous in patients with higher cardiovascular risk, such as obese patients.
      The primary outcome objective of this study was to test whether, in comparison
      with the endotracheal tube (ETT), the ProsealTM Laryngeal Mask Airway (PLMATM)
      (Laryngeal Mask Airway Company, Jersey, United Kingdom) reduces blood pressure
      and norepinephrine responses and the amounts of muscle relaxants needed in obese
      patients. METHODS: We assessed hemodynamic and hormonal stress responses,
      ventilation, and postoperative recovery in 75 morbidly obese patients randomized
      to receive standardized anesthesia with either an ETT or the PLMATM for
      laparoscopic gastric banding. RESULTS: In repeated-measures ANOVA, mean arterial
      blood pressure and plasma norepinephrine were significantly higher in the ETT
      group than in the PLMATM group. In individual pairwise comparisons, blood
      pressure rose higher in ETT than PLMATM patients after insertion and removal of
      airway devices, and after recovery. In ETT compared with PLMATM patients, plasma
      norepinephrine was higher after induction of carboperitoneum (mean +/- SD, 534 +/
      198 and 368 +/- 147 and pg/ml, P = 0.001), after airway device removal (578 +/-
      285 and 329 +/- 128 pg/ml, P < 0.0001), and after recovery in postanesthesia care
      unit (380 +/- 167 and 262 +/- 95 and pg/ml, P = 0.003). Compared with use of the
      ETT, the PLMATM reduced cisatracurium requirement, oxygen desaturation, and time
      to discharge from both the postanesthesia care unit and the hospital.
      CONCLUSIONS: PLMATM reduces stress responses and postoperative complaints after
      laparoscopic gastric banding.

PMID- 22614133
TI  - Circulating myeloid-derived suppressor cells are increased and correlate to
      immune suppression, inflammation and hypoproteinemia in patients with cancer.
AB  - Recent studies have identified myeloid-derived suppressor cells (MDSCs) that are
      potent suppressors of tumor immunity and therefore a significant impediment to
      cancer immunotherapy. It has been reported that MDSCs are generated by malignant
      diseases or inflammation. However, no systematic studies in patients have been
      described. In order to clinically characterize MDSCs, we tested PBMCs from
      patients with various types of cancer including cholangiocellular, hepatocellular
      and pancreatic carcinoma, esophageal, gastric and colorectal cancer, breast
      cancer and thyroid cancer, and GIST, and those from normal volunteers using flow
      cytometry analysis. A significant increase was seen in the percentages of MDSCs
      in PBMCs from patients compared with normal volunteers. Among these patients,
      MDSC level was higher in patients with cancer of the digestive system and
      patients with breast cancer compared with normal volunteers. MDSC level was
      significantly and inversely correlated to stimulation indices (SI) of PHA
      blastogenesis of lymphocytes and serum concentration of total protein, and
      positively correlated to neutrophil count. MDSC percentage in patients with
      gastric and colorectal cancer was also significantly correlated to neutrophil
      count and inversely correlated with lymphocyte count, and showed highly
      significant correlation to neutrophil/lymphocyte rate (NLR). In patients with
      breast cancer, MDSC levels in preoperative patients was significantly increased
      compared to normal volunteers and significantly decreased in postoperative
      patients. Thus, it is clear that MDSCs are increased in patients with cancer and
      closely related to suppression of cell-mediated immune responses. These data also
      suggest that they are related to chronic inflammation and that their levels are
      increased further in the terminal stages of patients whose nutritional status is
      impaired as observed in hypoproteinemia. MDSC levels have also been shown to
      decrease after removal of tumors in patients with breast cancer.

PMID- 22614134
TI  - Experimental comparison of connectivity measures with simulated EEG signals.
AB  - Directional connectivity measures exist with different theoretical backgrounds,
      i.e., information theoretic, parametric-modeling based or phase related. In this
      paper, we perform the first comparison in this extend of a set of conventional
      and directed connectivity measures [cross-correlation, coherence, phase slope
      index (PSI), directed transfer function (DTF), partial-directed coherence (PDC)
      and transfer entropy (TE)] with eight-node simulation data based on real resting
      closed eye electroencephalogram (EEG) source signal. The ability of the measures
      to differentiate the direct causal connections from the non-causal connections
      was evaluated with the simulated data. Also, the effects of signal-to-noise ratio
      (SNR) and decimation were explored. All the measures were able to distinguish the
      direct causal interactions from the non-causal relations. PDC detected less non
      causal connections compared to the other measures. Low SNR was tolerated better
      with DTF and PDC than with the other measures. Decimation affected most the
      results of TE, DTF and PDC. In conclusion, parametric-modeling-based measures
      (DTF, PDC) had the highest sensitivity of connections and tolerance to SNR in
      simulations based on resting closed eye EEG. However, decimation of data has to
      be carefully considered with these measures.

PMID- 22614135
TI  - Application of recurrence quantification analysis to automatically estimate
      infant sleep states using a single channel of respiratory data.
AB  - Previous work has identified that non-linear variables calculated from
      respiratory data vary between sleep states, and that variables derived from the
      non-linear analytical tool recurrence quantification analysis (RQA) are accurate
      infant sleep state discriminators. This study aims to apply these discriminators
      to automatically classify 30 s epochs of infant sleep as REM, non-REM and wake.
      Polysomnograms were obtained from 25 healthy infants at 2 weeks, 3, 6 and 12
      months of age, and manually sleep staged as wake, REM and non-REM. Inter-breath
      interval data were extracted from the respiratory inductive plethysmograph, and
      RQA applied to calculate radius, determinism and laminarity. Time-series
      statistic and spectral analysis variables were also calculated. A nested cross
      validation method was used to identify the optimal feature subset, and to train
      and evaluate a linear discriminant analysis-based classifier. The RQA features
      radius and laminarity and were reliably selected. Mean agreement was 79.7, 84.9,
      84.0 and 79.2 % at 2 weeks, 3, 6 and 12 months, and the classifier performed
      better than a comparison classifier not including RQA variables. The performance
      of this sleep-staging tool compares favourably with inter-human agreement rates,
      and improves upon previous systems using only respiratory data. Applications
      include diagnostic screening and population-based sleep research.

PMID- 22614136
TI  - Multiparametric bifurcations of an epidemiological model with strong Allee
      effect.
AB  - In this paper we completely study bifurcations of an epidemic model with five
      parameters introduced by Hilker et al. (Am Nat 173:72-88, 2009), which describes
      the joint interplay of a strong Allee effect and infectious diseases in a single
      population. Existence of multiple positive equilibria and all kinds of
      bifurcation are examined as well as related dynamical behavior. It is shown that
      the model undergoes a series of bifurcations such as saddle-node bifurcation,
      pitchfork bifurcation, Bogdanov-Takens bifurcation, degenerate Hopf bifurcation
      of codimension two and degenerate elliptic type Bogdanov-Takens bifurcation of
      codimension three. Respective bifurcation surfaces in five-dimensional parameter
      spaces and related dynamical behavior are obtained. These theoretical conclusions
      confirm their numerical simulations and conjectures by Hilker et al., and reveal
      some new bifurcation phenomena which are not observed in Hilker et al. (Am Nat
      173:72-88, 2009). The rich and complicated dynamics exhibit that the model is
      very sensitive to parameter perturbations, which has important implications for
      disease control of endangered species. 

PMID- 22614137
TI  - Electromyographic activity of lower limbs to stop baseball batting.
AB  - We investigated the muscle activation pattern of the lower limbs for the stopping
      motion of baseball batting by recording surface electromyography (EMG) from 8
      muscles, the left and right rectus femoris (RF), biceps femoris (BF), tibialis
      anterior (TA), and medial gastrocnemius (MG) muscles. First, muscle activities
      for 'Swing' and 'Stopping' trials were examined in 10 skilled baseball players
      and 10 unskilled novices. Second, the characteristics of EMG activities for
      'Stopping' were compared between the 2 groups. The peak latencies of EMG were
      significantly shorter in 'Stopping' than in 'Swing' at the right-TA, left-BF, and
      left-MG between both groups. The peak amplitudes of EMG activity were
      significantly larger in 'Swing' than in 'Stopping' at the right-TA, left-BF, and
      left-MG in both groups. In addition, the peak amplitudes of EMG activity for
      'Stopping' were significantly larger in the players than in novices at the right
      RF and right-TA. The characteristics of EMG activity clearly differed between
      'Swing' and 'Stopping,' and between baseball players and nonplayers, indicating
      that evaluating the EMG activity in batting enables the understanding of
      proficiency. Our findings should help players, novices, and coaches to optimize
      batting performance.

PMID- 22614138
TI  - Analysis of motor activities of professional soccer players.
AB  - The objective of this study was to determine the distance covered by professional
      soccer players during matches with the use of the computerized match analysis
      system Amisco Pro(r) (version 1.0.2, Nice, France). Kinematic examination
      included the specification of the distance covered by 31 players participating in
      4 matches in the Union of European Football Association Cup competitions during
      the 2008-2009 season. Data were analyzed based on players' positions on the
      pitch, changes in the players' motor activity intensity level, and match period
      (first or second half). The results of statistical analysis revealed that the
      average total distance covered by all players (n = 31) was 11,288 +/- 734 m. With
      respect to the player's position on the pitch, the midfielders traveled the
      longest average distance (11,770 +/- 554 m) during the game. This was 3% longer
      than the distance achieved by the attackers at 11,377 +/- 584 m, and 7% longer
      than that achieved by the defenders 10,932 +/- 728 m. The analysis of physical
      loads on soccer players during a match is highly useful for training
      individualization. It provides a tool for effective planning and for recording
      the loads on players, which is an indispensable element of modern coaching.

PMID- 22614139
TI  - Technical and tactical analysis of youth taekwondo performance.
AB  - This study aimed to analyze the technical and tactical aspects of young athletes
      during official taekwondo competitions. Fifty-nine youth taekwondo athletes (43
      boys and 16 girls; age range: 10-12 years; weight category range: <24 to >59 kg)
      with at least 2 years of taekwondo training consisting of three 90-minute
      training sessions for 3 d.wk-1 participated in this study. Thirty-seven matches
      (three 1-minute rounds, with 1-minute rest in between) were analyzed to verify
      the differences (p <= 0.05) in offensive and defensive actions in relation to
      gender (male, female), match outcome (winners, nonwinners), kicking leg (front,
      rear), and round (first, second, third). No difference emerged for gender and
      match outcome. With respect to defensive actions (8.4 +/- 12.0%), youth athletes
      engaged more frequently (p < 0.0001) in offensive actions (91.6 +/- 12.0%), which
      showed a significant decrease (p < 0.016) from the first round (42.3 +/- 21.8%)
      to the second (33.1 +/- 14.8%) and third (24.5 +/- 16.0%) ones. Kicks performed
      with the rear leg (94.4 +/- 7.8%) occurred more frequently (p < 0.0001) than
      those performed with the front leg (5.6 +/- 7.8%). In considering that a high
      level of coordination is required to perform front-leg kicks and defensive
      actions necessitate a high level of tactical skills, these findings might
      indicate a not-yet complete attainment of fundamental coordinative capabilities
      in 10- to 12-year-old athletes, independently of match outcome. To enhance
      coordination capabilities in youth athletes, coaches are recommended to structure
      their training including skill-ability and sport-ability drills.

PMID- 22614140
TI  - Validation of physiological tests in relation to competitive performances in
      elite male distance cross-country skiing.
AB  - The purpose of the present study was to establish which physiological test
      parameters reflects the distance performances in the Swedish National
      Championships in cross-country skiing (SNC) and the International Ski
      Federation's ranking points for distance performances (FISdist). The present
      study also aimed to create multiple regression models to describe skiing
      performance for the SNC distance races and International Ski Federation's (FIS)
      ranking. Twelve male, Swedish, national elite, cross-country skiers (maximal
      oxygen consumption [.VO2max] = 5.34 +/- 0.34 L.min-1) volunteered to participate
      in the study. Their results in the 2008 SNC (15 km race [SNC15] and 30 km race
      [SNC30]) and FISdist points were used as performance data. On the week preceding
      the Championship, subjects completed a test battery consisting of 7 physiological
      tests: isokinetic knee extension peak torque (PT), vertical jumps (VJ), lactate
      threshold (LT), .VO2max, and 3 double poling tests of different durations (DP20,
      DP60, and DP360). Correlations were established using Pearson's correlation
      analysis, and models to describe skiing performance were created using standard
      multiple linear regression analysis. Significant correlations were found between
      the performance parameters and test parameters derived from LT, .VO2max, and DP60
      tests. No correlations with any performance parameter were found for PT, VJ,
      DP20, and DP360 tests. For FISdist and SNC15, the models explain 81% and 78% of
      the variance in performance, respectively. No statistically valid regression
      model was found for SNC30. The results of this study imply that the physiological
      demands in male elite distance cross-country skiing performances are different in
      different events. To adequately evaluate a skier's performance ability in
      distance cross-country skiing, it is necessary to use test parameters and
      regression models that reflect the specific performance.

PMID- 22614141
TI  - Body mass change and ultraendurance performance: a decrease in body mass is
      associated with an increased running speed in male 100-km ultramarathoners.
AB  - We investigated, in 50 recreational male ultrarunners, the changes in body mass,
      selected hematological and urine parameters, and fluid intake during a 100-km
      ultramarathon. The athletes lost (mean and SD) 2.6 (1.8) % in body mass (p <
      0.0001). Running speed was significantly and negatively related to the change in
      body mass (p < 0.05). Serum sodium concentration ([Na+]) and the concentration of
      aldosterone increased with increasing loss in body mass (p < 0.05). Urine
      specific gravity increased (p < 0.0001). The change in body mass was
      significantly and negatively related to postrace serum [Na+] (p < 0.05). Fluid
      intake was significantly and positively related to both running speed (r = 0.33,
      p = 0.0182) and the change in body mass (r = 0.44, p = 0.0014) and significantly
      and negatively to both postrace serum [Na+] (r = -0.42, p = 0.0022) and the
      change in serum [Na+] (r = -0.38, p = 0.0072). This field study showed that
      recreational, male, 100-km ultramarathoners dehydrated as evidenced by the
      decrease in >2 % body mass and the increase in urine-specific gravity. Race
      performance, however, was not impaired because of the loss in body mass. In
      contrast, faster athletes lost more body mass compared with slower athletes while
      also drinking more. The concept that a loss of >2% in body mass leads to
      dehydration and consequently impairs endurance performance must be questioned for
      ultraendurance athletes competing in the field. For practical applications, a
      loss in body mass during a 100-km ultramarathon was associated with a faster
      running speed.

PMID- 22614142
TI  - Basketball ability testing and category for players with mental retardation:  8
      month training effect.
AB  - Although sport for athletes with mental retardation (MR) is achieving an
      important role, the literature concerning basketball tests and training is still
      poor. The aims of this study were to verify whether the basketball test battery
      could be an appropriate modality to classify the players in the Promotion (Pro)
      category, to assess basketball abilities before (PRE) and after (POST) an 8-month
      training in players with MR in relation to Competitive (Comp) and Pro categories,
      to analyze the variation of specific basketball abilities based on subjects' MR
      diagnosis. Forty-one male basketball players with MR (17 Comp and 24 Pro; age
      range 18-45 years; MR: 15% mild, 54% moderate, 29% severe, and 2% profound) were
      assessed PRE and POST training through the basketball test battery, which
      assessed 4 ability levels of increasing difficulty (from I to IV), each one
      characterized by the analysis of fundamental areas (ball handling, reception,
      passing, and shooting). Level I was significantly changed after the intervention
      period regardless of the Category, whereas shooting was affected by the
      interaction between Category and Intervention. The results showed significant
      differences between categories in the scores of individual global, level I, level
      II, level III, and in all fundamental areas. Individual global score in both
      categories significantly increased. The players of Comp significantly improved in
      level III, in ball handling, reception, passing, and shooting scores. The players
      of Pro improved significantly in level II, in ball handling, reception, and
      passing scores. Individual global, ability levels I-III, and fundamental area
      scores were negatively correlated to the MR level indicating that the players
      with a lower MR obtained higher ability scores. In conclusion, it was found that
      the basketball test battery could be useful for improving and monitoring training
      in both Comp and Pro players.

PMID- 22614143
TI  - Effect of two different long-sprint training regimens on sprint performance and
      associated metabolic responses.
AB  - The purpose of this study was to analyze 2 different long-sprint training
      programs (TPs) of equal total work load, completed either with short recovery
      (SR) or long recovery (LR) between sets and to compare the effects of 6 long
      sprint training sessions (TSs) conducted over a 2-week period on a 300-m
      performance. Fourteen trained subjects performed 3 pretraining maximal sprints
      (50-, 100-, and 300-m), were paired according to their 300-m performance, and
      randomly allocated to an LR or SR group, which performed 6 TSs consisting of sets
      of 150, 200, or 250 m. The recovery in the LR group was double that of the SR
      group. During the third TS and the 300-m pretest and posttest, blood pH,
      bicarbonate concentration ([HCO3-]), excess-base (EB), and lactate concentration
      were recorded. Compared with a similar TS performed with SR, the LR training
      tends to induce a greater alteration of the acid-base balance: pH: 7.09 +/- 0.08
      (LR) and 7.14 +/- 0.05 (SR) (p = 0.10), [HCO3-]: 7.8 +/- 1.9 (LR) and 9.6 +/- 2.7
      (SR) (p = 0.04), and EB: -21.1 +/- 3.8 (LR) and -17.7 +/- 2.8 (SR) (p = 0.11). A
      significant improvement in the 300-m performance between pre-TP and post-TP
      (42.45 +/- 2.64 vs. 41.52 +/- 2.45, p = 0.01) and significant decreases in pH (p
      < 0.01), EB (p < 0.001) and increase in [La] (p < 0.001) have been observed post
      TP compared with those pre-TP. Although sprint training with longer recovery
      induces higher metabolic disturbances, both sprint training regimens allow a
      similar 300-m performance improvement with no concomitant significant progress in
      the 50- and 100-m performance.

PMID- 22614144
TI  - The effects of two stretching protocols on the reactive strength index in female
      soccer and rugby players.
AB  - The purpose of this study was to investigate the effects of 2 stretching
      protocols on stretch-shortening cycle performance in female Division I soccer
      players and female club rugby players. Fifteen soccer and rugby players (20.1 +/-
      5.9 years, 170.5 +/- 14.2 cm, 70.4 +/- 22.3 kg) participated in 3 test sessions
      with different treatments. The first treatment involved a warm-up of 10 minutes
      of exercise on a cycle ergometer (warm-up only [WO]), the second was this warm-up
      followed by static stretching (SS), and the third was this warm-up followed by
      dynamic stretching (DS). The treatments were administered randomly to negate an
      order effect. Each treatment was immediately followed by a reactive strength
      index (RSI) test requiring the athletes to drop off a box (45 cm in height) on to
      a force plate and upon landing immediately jump into the air while minimizing
      contact time (CT, milliseconds) and maximizing flight time (FT, milliseconds).
      The RSI was FT: CT. Repeated measures analysis of variance indicated that a
      significant treatment effect existed for RSI (F = 7.95, 2; p = 0.002) and FT (F =
      7.43, 2; p = 0.003) but no significant effect for CT (F = 1.53, 2; p = 0.235).
      The RSI and FT were significantly greater in DS compared with that in SS and WO.
      Dynamic stretching is the preferred warm-up before an athletic event involving
      considerable jumping.

PMID- 22614145
TI  - Three-dimensional kinematic analysis of the snatch technique for lifting
      different barbell weights.
AB  - The purpose of this study was to investigate the effects of increased barbell
      loads on barbell and body kinematics of the snatch lifts at 60, 80, and 100% of 1
      repetition maximum and to evaluate the biomechanics of snatch technique. The
      study was performed on 7 elite male weightlifters of the Turkish national team.
      Four cameras operating at 50 fields per second were used to record the lifts. For
      3D kinematic analysis of center of gravity (CG) and barbell movement, the points
      on the body and the barbell were digitized by using an Ariel Performance Analysis
      System. There were significant differences between the vertical work values (p <
      0.05). The power values of the 3 snatch lifts were also found to be significantly
      different (p < 0.05). Another significant difference (p < 0.05) was observed
      between maximum vertical displacement of the barbell, maximum vertical velocity
      of the barbell, maximum vertical displacement of CG, the vertical velocity of CG
      during the turnover under the barbell. The results demonstrated that vertical and
      horizontal kinematics of the barbell and body decreased at the pull phase of the
      snatch technique as the barbell load increased. The power output during the
      second pull increased although the work done did not change, whereas work and
      power output increased during the first pull phase depending on the increase in
      the barbell weight. The finding of this study suggested that weightlifters had to
      perform the turnover under the barbell and the catch phase faster, because when
      the barbell weight was increased at snatch lift, vertical kinematics of the
      barbell decreased.

PMID- 22614146
TI  - Peak power, force, and velocity during jump squats in professional rugby players.
AB  - Training at the optimal load for peak power output (PPO) has been proposed as a
      method for enhancing power output, although others argue that the force,
      velocity, and PPO are of interest across the full range of loads. The aim of this
      study was to examine the influence of load on PPO, peak barbell velocity (BV),
      and peak vertical ground reaction force (VGRF) during the jump squat (JS) in a
      group of professional rugby players. Eleven male professional rugby players (age,
      26 +/- 3 years; height, 1.83 +/- 6.12 m; mass, 97.3 +/- 11.6 kg) performed loaded
      JS at loads of 20-100% of 1 repetition maximum (1RM) JS. A force plate and linear
      position transducer, with a mechanical braking unit, were used to measure PPO,
      VGRF, and BV. Load had very large significant effects on PPO (p < 0.001, partial
      eta2 = 0.915); peak VGRF (p < 0.001, partial eta2 = 0.854); and peak BV (p <
      0.001, partial eta2 = 0.973). The PPO and peak BV were the highest at 20% 1RM,
      though PPO was not significantly greater than that at 30% 1RM. The peak VGRF was
      significantly greater at 1RM than all other loads, with no significant difference
      between 20 and 60% 1RM. In resistance trained professional rugby players, the
      optimal load for eliciting PPO during the loaded JS in the range measured occurs
      at 20% 1RM JS, with decreases in PPO and BV, and increases in VGRF, as the load
      is increased, although greater PPO likely occurs without any additional load.

PMID- 22614148
TI  - Effect of conjugated linoleic acid on testosterone levels in vitro and in vivo
      after an acute bout of resistance exercise.
AB  - The purposes of the present study were to investigate the effect of conjugated
      linoleic acid (CLA) supplementation on testosterone levels in vitro on a cell
      line derived from Leydig cells (R2C) and in vivo in the blood of physically
      active subjects before and after a resistance exercise bout. In vitro R2C cells
      were treated with different CLA concentrations (0-30 MUM) for 24 and 48 hours.
      After treatment, supernatant media were tested to determine testosterone
      secretion. The CLA increased the testosterone secretion only after 48 hours. In
      vivo, 10 resistance-trained male subjects, in a double-blind placebo-controlled
      and crossover study design were randomized for 3 weeks of either 6 g.d-1 CLA or
      placebo. Blood was drawn pre and post each resistance exercise bout to determine
      the total testosterone and sex hormone-binding globulin (SHBG) levels. No
      significant differences were observed for total testosterone or SHBG pre and post
      each resistance exercise bout; although after the resistance exercise bouts,
      total testosterone increased moderately (effect size = moderate), whereas after
      CLA supplementation, there was a large increase in total testosterone (effect
      size = large). CLA supplementation induced an increase in testosterone levels in
      Leydig cells in vitro after 48 hours but not in vivo before and after a
      resistance exercise bout. These findings suggest that CLA supplementation may
      promote testosterone synthesis through a molecular pathway that should be
      investigated in the future, although this effect did not have an anabolic
      relevance in our in vivo model.

PMID- 22614149
TI  - Effects of repeated bouts of supramaximal exercise on plasma adiponectin,
      interleukin-6, and tumor necrosis factor-alpha levels in sedentary men.
AB  - The objective of the study was to determine the effects of repeated bouts of
      supramaximal exercise on plasma adiponectin, interleukin (IL)-6 and tumor
      necrosis factor (TNF)-alpha levels in sedentary men. Fourteen healthy,
      nonsmoking, and sedentary men aged between 18.4 and 21.4 years participated in
      the study. All the subjects performed 5 Wingate tests (WTs) with 75 g per
      kilogram body weight load with 2-minute intervals between the tests. Blood
      samples were collected at preexercise, immediately after, 15 and 60 minutes after
      the fifth WT. Serum and plasma samples were stored at -80 degrees C until the
      time of analysis for myoglobin, adiponectin, IL-6, and TNF-alpha. Plasma
      adiponectin levels decreased, whereas IL-6 levels increased postexercise compared
      with that preexercise. The TNF-alpha levels were not changed with supramaximal
      exercise. In conclusion, repeated bouts of supramaximal exercise cause an
      inflammatory response in exercised muscle and increase in plasma IL-6 levels and
      decrease in adiponectin concentrations.

PMID- 22614147
TI  - Reduced ribosomal protein s6 phosphorylation after progressive resistance
      exercise in growing adolescent rats.
AB  - The purpose of this study was to investigate moderate intensity progressive
      resistance exercise (PRE) in growing adolescent rats and its effect on muscle
      hypertrophy (defined as an increase in fiber cross-sectional area [CSA]). We
      hypothesized that in adolescent animals moderate intensity PRE would increase (a)
      fiber CSA; (b) myosin heavy chain (MyHC) content; and (c) expression and
      phosphorylation of cell signaling molecules involved in translational regulation,
      compared with that in age-matched sedentary (SED) controls. In the PRE group, 3
      week-old male rats were trained to climb a vertical ladder as a mode of PRE
      training such that by 10 weeks all animals in the PRE group had progressed to
      carry an additional 80% of their body weight per climb. In agreement with our
      hypotheses, we observed that 10 weeks of moderate PRE in adolescent animals was
      sufficient to increase the CSA of muscle fibers and increase MyHC content. The
      average muscle fiber CSA increased by >10%, and the total MyHC content increased
      by 35% (p < 0.05) in the PRE group compared with that in the SED animals.
      Concurrently, we investigated sustained changes in the expression and
      phosphorylation of key signaling molecules that are previously identified
      regulators of hypertrophy in adult animal models. Contrary to our hypotheses,
      expression and phosphorylation of the translational regulators mammalian target
      of rapamycin and Akt were not increased in the PRE group. In addition, we
      observed that the ratio of phosphorylated-to-unphosphorylated ribosomal protein
      S6 (rpS6) was reduced over sixfold in PRE animals (p < 0.05) and that total rpS6
      protein levels were unchanged between PRE and SED animals (p > 0.05). We conclude
      that moderate intensity PRE is sufficient to induce muscle hypertrophy in
      adolescent animals, whereas the signaling mechanisms associated with muscle
      hypertrophy may differ between growing adolescents and adults.

PMID- 22614150
TI  - Effects of carbohydrate supplementation on force output and time to exhaustion
      during static leg contractions superimposed with electromyostimulation.
AB  - The purpose of this study was to investigate the effects of carbohydrate
      ingestion on force output and time to exhaustion using single leg static
      contractions superimposed with brief periods of electromyostimulation. Six
      trained male subjects participated in a randomized, counterbalanced, double-blind
      study. The subjects were randomly assigned to placebo (PL) or carbohydrate (CHO).
      The subjects in CHO consumed 1 g of carbohydrate per kilogram of body mass
      loading dose and 0.17 g of carbohydrate per kilogram of body mass every 6 minutes
      during the exercise protocol. The PL received an equal volume of a solution made
      of saccharin and aspartame. The exercise protocol consisted of repeated 20-second
      static contractions of quadriceps muscle at 50% maximal voluntary contraction
      followed by 40-second rest until failure occurred. Importantly, the force output
      during quadriceps maximal voluntary contraction strength with superimposed
      electromyostimulation was measured in the beginning and every 5 minutes during
      the last 3 seconds of static contractions throughout the exercise protocol.
      Venous blood samples were taken preexercise, immediately postexercise, and at 5
      minutes postexercise and analyzed for blood lactate. Our results indicate that
      time to exhaustion (PL = 16.0 +/- 8.1 minutes; CHO = 29.0 +/- 13.1 minutes) and
      force output (PL = 3,638.7 +/- 524.5 N; CHO = 5,540.1 +/- 726.1 N) were
      significantly higher (p < 0.05) in CHO compared with that in PL. Data suggest
      that carbohydrate ingestion before and during static muscle contractions can
      increase force output and increase time to exhaustion. Therefore, our data
      suggest that carbohydrate supplementation before and during resistance exercise
      might help increase the training volume of athletes.

PMID- 22614151
TI  - Intramolecular hydrogen atom migration along the backbone of cationic and neutral
      radical tripeptides and subsequent radical-induced dissociations.
AB  - Dissociation of peptide radical ions involves competition between charge-induced
      and radical-induced reactions that can be preceded by isomerization. The isomeric
      radical cations of the peptide methyl ester [GGR-OMe](+) and [GGR-OMe](+) provide
      very similar collision-induced dissociation (CID) spectra, suggesting that
      isomerization occurs prior to fragmentation. They undergo characteristic radical
      induced bond cleavage of the peptide N-terminal amide bond resulting in the y2(+)
      ion, and of the arginine side-chain's Calpha-Cbeta bond giving protonated
      allylguanidine {[CH2[double bond, length as m-dash]CHCH2NHC(NH2)2](+), m/z 100}.
      The absence of a y2(+) fragment ion in the CID of the radical cationic tripeptide
      [ACH3GR](+) and of an m/z 100 ion in the spectrum of [GACH3R](+) (where ACH3 is
      an alpha-aminoisobutyric acid residue, which cannot form an alpha-carbon-centered
      radical through hydrogen atom transfer) establishes the importance of hydrogen
      atom migration along the peptide backbone prior to specific radical-induced
      fragmentations. Herein we use density functional theory (DFT) at the B3LYP/6
      31++G(d,p) level to evaluate the barriers for interconversion between the alpha
      carbon-centered radicals and for dissociation. The radical cations [GGR](+) and
      [GGR](+) have their radicals located on the alpha-carbon atoms of the peptide
      backbone and their charge densities largely sequestered on the guanidine groups
      of the side-chain of arginine residues. This is in contrast to the isomeric
      radical cations of [GGG](+), in which the charge resides necessarily on the
      peptide backbone. The lower charge densities on the backbones of [GGR](+) and
      [GGR](+) result in greater structural flexibility, decreasing the barrier for
      interconversion between these alpha-carbon-centered radicals to 36.2 kcal mol(-1)
      (cf. 44.7 kcal mol(-1) for [GGG](+)). The total absence of charge, assessed by
      examining intramolecular hydrogen atom transfers among the three alpha-carbon
      centers of the isomeric neutral alpha-carbon-centered triglycine radicals [GGG
      H], leads to an additional but slight reduction in enthalpy, to approximately 34
      kcal mol(-1). 

PMID- 22614152
TI  - Effect of chronic inhibition of converting enzyme on renal handling of salt and
      water: a study on a pediatric population.
AB  - BACKGROUND/AIMS: The effect of angiotensin-converting enzyme inhibition (ACEi) is
      amply documented in several pathological conditions. However, there are few
      reports about the effect of chronic ACEi on salt and water balance.The present
      work evaluates the effect of chronic ACEi on salt and water balance in a
      population of children receiving enalaprilchronically in order to reduce
      albuminuria elicited by auremic hemolytic syndrome. METHODS: Nine children aged
      from 9 to 19 years with normal glomerular filtration rate, normotension and with
      urinary concentration capacity preserved were treated with enalapril with doses
      ranging between 0.1 and 0.30 mg/kg/day. Diuresis, urinary absolute and fractional
      excretion of Na(+), K(+) and urea, creatinine clearance,osmolal clearance and
      tubular water reabsorption were measured under three experimental procedures:
      (1)with free access to water; (2) with a water load and (3) with water
      restriction. In the last group urinary antidiuretic hormone(ADH) was measured.
      These tests were performed ina paired way, just before starting ACEi treatment
      and after 6 months of enalapril treatment. RESULTS: Enalapril treatment
      diminished the urinary concentration capacity without affecting Na(+) and K(+)
      urinary excretion. Creatinine clearance was not modified except in the condition
      of water load where a fall in it was found after ACEi. ADH increased after
      enalapril treatment in children under water restriction. CONCLUSION: In these
      children chronic ACEi decreases urinary concentration capacity.

PMID- 22614153
TI  - High mortality in late octogenarians undergoing isolated aortic valve replacement
      for aortic valve stenosis: EuroSCORE underestimates mortality in this cohort.
AB  - OBJECTIVES: Considering the expanding technology of catheter-based aortic valve
      implantation, high-risk patients who would not be suitable for conventional
      aortic valve replacement (AVR) should be identified. METHODS: From 1997 to April
      2007, 190 patients aged from 80 and 89 years old received isolated AVR. Patients
      between 80 and 84 years old were categorized as the early octogenarians (n = 148)
      and patients between 85 and 89 years old were categorized as the late
      octogenarians (n = 42). RESULTS: Thirty days mortality in the early and late
      octogenarians were 6 and 21%, respectively (p = 0.003). The additive and logistic
      EuroSCORE were 8.0 +/- 2.4 and 8.8 +/- 1.8 in the early octogenarians and 13.2 +/
      11.8 and 14.6 +/- 8.7 in the late octogenarians. Multivariate analysis revealed
      the late octogenarians (OR 6.7, 95%CL 1.8-24.4, p = 0.004) and poor left
      ventricular function (OR 8.0, 95%CL 1.2-53.5, p = 0.032) as significant risk
      factors for 30 days mortality. Early octogenarians showed 1-year, 3-year, 5-year,
      and 8-year survival of 82.4, 67.6, 54.7, and 33%, respectively. Late
      octogenarians showed 1-year, 3-year, 5-year, and 8-year survivals of 69.0, 66.2,
      41.6, 22.3%, respectively. CONCLUSIONS: Mortality after AVR in the late
      octogenarians was very high, and was underestimated by EuroSCORE in this patients
      group. In late octogenarians, catheter-based aortic valve implantation despite
      relative low EuroSCORE level could be considered as a reasonable alternative.

PMID- 22614154
TI  - Comparison of the efficacy and the toxicity between gemcitabine with capecitabine
      (GC) and gemcitabine with erlotinib (GE) in unresectable pancreatic cancer.
AB  - OBJECTIVE: We retrospectively compared the efficacy and toxicity of gemcitabine
      combination with capecitabine or erlotinib in unresectable pancreatic cancer to
      know whether the combination with cytotoxic and target agent has more benefit
      comparing to combination of cytotoxic agents. METHODS: Fifty-three patients with
      unresectable pancreatic cancer, treated with gemcitabine and capecitabine (GC) or
      gemcitabine and erlotinib (GE) as first line between October 2006 and July 2010,
      were reviewed. In GC group, patients were treated with gemcitabine 1,000 mg/m(2)
      on days 1, 8, and capecitabine 1,300 mg/m(2) bid was administered on days 1-14,
      repeated every 21 days. In GE group, gemcitabine was given at 1,000 mg/m(2) I.V
      for 30 min on days 1,8,15, and erlotinib was taken orally at 100 mg through days
      1-28, repeated every 28 days. RESULTS: Response rate was similar, 23.5 % in GE
      and 21.1 % in GC, but GC had better disease control rate with 73.7 % than GE with
      52.9 %. GC also showed longer PFS and OS (5.37 and 14.43 months) than GE (2.63
      and 6.23 months) (p = 0.032 for PFS and 0.002 for OS). In toxicity profiles, GC
      had more hematologic toxicities and GE had more non-hematologic toxicities.
      CONCLUSIONS: The combination with cytotoxic agents seems to have better efficacy
      and clinical outcome than combination with cytotoxic agent and target agent. The
      new combination should be developed for the treatment for advanced pancreatic
      cancer.

PMID- 22614155
TI  - CD133 expression in renal cell carcinoma (RCC) is correlated with nuclear hypoxia
      inducing factor 1alpha (HIF-1alpha).
AB  - PURPOSE: In our previous study, we have found that the hypoxia-inducible factor
      1alpha (HIF-1alpha) is upregulated in renal cell carcinoma (RCC) tissues compared
      with para-cancer normal tissues by 2-dimensional polyacrylamide gel
      electrophoresis. It was reported that hypoxic conditions were correlated with
      cancer stem cell generation and HIF-1alpha acted as a transcription regulator in
      nuclear HIF-1alpha expression. Therefore, in this study we investigate the
      relation between CD133 and nuclear HIF-1alpha expression levels in RCC tissues.
      METHODS: In this study 61 RCC tissues from the patients that treated with radical
      nephrectomy were collected. Then, we investigated the expression of CD133 and
      nuclear HIF-1alpha expression by immunohistochemistry. To verify the relation
      between CD133 and nuclear HIF-1alpha expression, we treated 786-O cells with
      cobalt chloride. The expression of CD133 on 786-O cells was analyzed by
      flowcytometry. RESULTS: The immunohistochemical study showed that CD133 was
      correlated with tumor stage and metastatic stage, whereas nuclear HIF-1alpha had
      no association with clinicopathological parameters. However, the expression of
      nuclear HIF-1alpha was correlated with CD133. The CD133 expression in 786-O cells
      was enhanced by cobalt chloride, which meant that CD133 expression was affected
      by hypoxia. CONCLUSIONS: Our study showed that in RCC, CD133 expression was
      strongly related to nuclear HIF-1alpha and the expression of CD133 might be
      upregulated under hypoxia environment.

PMID- 22614156
TI  - Prognostic value of tumor progression-related gene expression in colorectal
      cancer patients.
AB  - PURPOSE: Colorectal cancer (CRC) is driven by genetic alterations causing its
      progression. Besides accepted tumor suppressor- and onco- genes, a series of
      genes have been identified, which contribute to transformation into a more
      malignant stage. We investigated whether the expression level of such genes,
      alone or in combination, could add to predict the prognosis of CRC patients.
      METHODS: Tumor samples from 118 CRC patients were screened in a retrospective
      analysis by qRT-PCR for expression of the four tumor progression-associated genes
      osteopontin (Opn), transforming growth factor beta (Tgf-beta), matrix
      metalloproteinase-2 (Mmp-2) and cyclooxigenase-2 (Cox-2). The resulting qRT-PCR
      values were related to those of housekeeping genes. All patients were clustered
      for similar expression levels between the four genes with R statistical software
      using the package pvclust, which provides bootstrap agglomerative hierarchical
      clustering. Clusters with similar expression of the four genes were analyzed for
      correlation with UICC stages and survival time. RESULTS: Expression of the four
      genes varied considerably within the cohort of patients. Cluster analysis of
      patients revealed a subgroup (n = 33) who in comparison with the other patients
      showed tenfold higher expression levels of all four genes (p < 0.001,
      respectively). However, there was no correlation between patients expressing high
      or low levels of these four genes and known parameters of clinical prognosis
      (UICC stages, survival time). CONCLUSIONS: In conclusion, tenfold increased
      expression levels of Opn, Tgf-beta, Mmp-2 and Cox-2 in a subset of CRC patients
      did not predict for a clinical outcome that is different from that of the
      remaining patients.

PMID- 22614157
TI  - Synergistic activity of the mTOR inhibitor ridaforolimus and the antiandrogen
      bicalutamide in prostate cancer models.
AB  - Although androgen ablation therapy is the foundation of current prostate cancer
      treatment, most patients ultimately develop castration-resistant disease. One
      proposed mechanism to account for androgen receptor (AR) activity in the castrate
      environment is via crosstalk with other signaling pathways. Specifically,
      reciprocal interactions between the AKT/mTOR and AR pathways have been implicated
      in prostate cancer progression. Here, we used the potent inhibitor ridaforolimus
      to target mTOR signaling alone and in combination with AR blockade by
      bicalutamide to examine the effect of abrogating these signaling pathways.
      Ridaforolimus treatment inhibited the proliferation of all six prostate cancer
      cell lines examined with the greatest sensitivity associated with loss of PTEN
      and elevated AKT/mTOR pathway activity. Dual inhibition of the AR and mTOR
      signaling pathways provided further benefit with the ridaforolimus-bicalutamide
      combination producing synergistic antiproliferative effects in prostate cancer
      cells in vitro when compared with each agent alone. Pharmacodynamic analysis
      confirmed that combination treatment resulted in full inhibition of each of the
      respective pathways. Importantly, the ridaforolimus-bicalutamide combination
      exhibited potent antitumor activity with parallel reductions in plasma PSA levels
      in vivo. Taken together, ridaforolimus exhibited potent antiproliferative and
      antitumor activity in prostate cancer models and the addition of bicalutamide
      represents a potentially effective combination strategy for patient therapy.

PMID- 22614158
TI  - Fertility preservation in young women with breast cancer.
AB  - When a young woman is diagnosed with breast cancer, there is often a sense of
      urgency by the patient and her providers to initiate treatment. This article
      provides guidelines for incorporating the discussion of fertility preservation
      with newly diagnosed young women with breast cancer.

PMID- 22614161
TI  - Synthesis and evaluation of atropos dihydro-5H-dibenzazepinium halide PTCs
      derived from alpha-methylbenzylamine.
AB  - A short synthetic route to diastereoisomeric atropos dihydro-5H
      dibenz[c,e]azepinium salts via reaction of a single enantiomer of (R)-alpha
      methylbenzylamine with a racemic atropos biphenol derivative is described.
      Compounds prepared via this approach are used to provide strong evidence that
      structurally related tropos dihydro-5H-dibenz[c,e]azepinium salts preferentially
      react via a single conformation in PTC reactions involving glycine imine
      enolates.

PMID- 22614160
TI  - Influence of post-thaw culture on the developmental potential of human frozen
      embryos.
AB  - PURPOSE: Apart from freezing/thawing related cryodamage, several additional
      factors have been identified as major players in the reduction of success rates
      after frozen embryo transfers. The post-thaw culture is particularly relevant as
      it may amplify environmental influences over a stressed embryo. In the present
      study the influence of the post-thaw culture duration on the implantation and
      developmental potential of cleavage stage embryos was evaluated. METHODS: In this
      retrospective evaluation, that spanned an 8-year period, 631 frozen-thawed
      embryos were allocated to one of two study groups, depending on their post-thaw
      culture period: 1) the long (18-24 h), or 2) the short (2-5 h) culture group.
      Groups were compared regarding implantation rate and live birth rate per embryo
      transferred. This comparison was corrected for the most common confounding
      factors such as maternal age at oocyte pick-up, number of transferred embryos,
      developmental day at freezing, blastomere survival after thawing, catheter used
      for transfer and year of procedure. RESULTS: Implantation and live birth rate per
      embryo transferred were inversely related to the duration of the post-thaw
      culture, as diminishing this period significantly increased both rates. Moreover,
      no advantage could be found for a long post-thaw culture period, even for embryos
      with observed mitotic activity. CONCLUSION: This retrospective analysis indicates
      that a short post-thaw culture period is associated with higher implantation and
      live birth rates per embryo. This study supports selection of frozen-thawed
      embryos strictly based on blastomere cryosurvival and raises the hypothesis that
      environmental factors may have an important role on embryo implantation and
      developmental potential during post-thaw culture.

PMID- 22614162
TI  - FISH in pathology.

PMID- 22614159
TI  - Fertility considerations in young women with hematological malignancies.
AB  - The need for practice guidelines for fertility preservation in young women with
      hematological malignancies has been increased. To develop recommendations,
      publications relevant to fertility preservation and hematological cancers were
      identified through a PubMed database search and reviewed systematically, focusing
      on the effects of oncological treatments on fertility as well as on the efficacy,
      feasibility and risks of existing fertility preservation methods.

PMID- 22614163
TI  - Histopathological characterization of a Cameron lesion.
AB  - Cameron lesions are linear erosions located at the neck of a hiatal hernia (HH)
      in patients with a large HH. The prevalence has been seen in up to 5% of patients
      with HH who undergo esophagogastroduodenoscopy, and they can be associated with
      overt gastrointestinal bleeding or anemia. These lesions occur due to vascular
      compression by the diaphragm in a large sliding HH. Histopathologic changes seen
      in the biopsy tissue of a Cameron lesion are due to ischemia, but this ischemia
      is reversible with treatment of HH. The existence of this entity and the
      histopathologic picture of a Cameron lesion is not well known to pathologists,
      and therefore, a microscopic picture of a Cameron lesion can be easily confused
      with ischemic gastritis. Ischemic gastritis is the result of atherosclerosis,
      usually seen in older people, unrelated to HH, and is not easily reversible. The
      authors received a gastric biopsy of a hiatal hernia without any associated
      clinical diagnosis of a Cameron lesion conveyed to the pathologist. This biopsy
      tissue showed ischemic changes in the gastric mucosa on microscopic examination.
      Diagnosis of ischemic gastritis was considered but ruled out after the case was
      discussed with the gastroenterologist. The correct diagnosis was made once the
      clinical diagnosis of HH with Cameron lesion (ie, a vertical red erosion) was
      made known to the pathologist. By reporting this case, the authors aim to
      increase awareness of Cameron lesion among pathologists so that they ask about
      the presence of a Cameron lesion before making the diagnosis of ischemic
      gastritis.

PMID- 22614165
TI  - Neuroendocrine tumors of the submandibular gland: literature review and report of
      a case.
AB  - Primary salivary neuroendocrine neoplasms are extremely rare, with only 1 case of
      carcinoid tumor and 7 cases of primary large-cell neuroendocrine carcinomas
      having been reported. Salivary small-cell neuroendocrine carcinomas are more
      frequent, accounting for less than 2% of all salivary malignancies. In addition
      to a literature review on the subject, the authors describe a rare case of
      malignant intermediate-grade neuroendocrine tumor of the submandibular gland.

PMID- 22614164
TI  - Tumoral calcinosis--a pathogenetic overview: a histological and ultrastructural
      study with a report of two new cases, one in infancy.
AB  - Tumoral calcinosis occurs as a well-defined pathologic entity in 3 heterologous
      groups of diseases--hyperphosphatemic familial tumoral calcinosis,
      normophosphatemic tumoral calcinosis, and secondary tumoral calcinosis. The
      histological lesion is stereotypic developing from the concurrence of a juxta
      articular injury with an elevated calcium-phosphorus product. The reparative
      response to injury is histiocytic featuring synovial metaplasia forming bursa
      like structures that create the characteristic compartmentalization of the
      lesion. Histiocytic-derived osteoclastogenesis occurs as a response to the
      calcifying process initiated in the mitochondria of necrotic histiocytes forming
      the bursa-like structures. These calcifications, propelled by a gamut of
      conditions elevating serum phosphorus, facilitate the further nucleation of
      hydroxyapatite in mitochondria, matrical lipidic debris located in the cytoplasm
      and lysosomes of osteoclasts and in the locular contents, and on collagen and
      other extracellular matrix materials. The lesions enlarge because of new locule
      formation and failure to reduce the calcified burden by the compartment lining
      histiocytes and dysmorphic osteoclasts that are unable to solubilize the
      hydroxyapatite. The histological landmarks of tumoral calcinosis may be lost when
      its development becomes quiescent. The classic calcifying classifications are
      inadequate for tumoral calcinosis requiring creation of a new category for this
      entity.

PMID- 22614166
TI  - Giant occipital chondrosarcoma of 10 years duration in a 20-year-old man.

PMID- 22614168
TI  - Evaluation of the thermal effect on separation selectivity in anion-exchange
      processes using superheated water ion-exchange chromatography.
AB  - The thermal effect on retention and separation selectivity of inorganic anions
      and aromatic sulfonate ions in anion-exchange chromatography is studied on a
      quaternized styrene-divinylbenzene copolymer anion-exchange column in the
      temperature range of 40-120  degrees C using superheated water chromatography.
      The selectivity coefficient for a pair of identically charged anions approaches
      unity as temperature increases provided the ions have the same effective size,
      such that the retention of an analyte ion decreases with an increase in
      temperature when the analyte ion has stronger affinity for the ion-exchanger than
      that of the eluent counterion, whereas it increases when it has weaker affinity.
      The change in anion-exchange selectivity with temperature observed with
      superheated water chromatography has been discussed on the basis of the effect of
      temperature on hydration of the ions. At elevated temperatures, especially in
      superheated water, the electrostatic interaction or association of the ions with
      the fixed ion in the resin phase becomes a predominant factor resulting in a
      different separation selectivity from that obtained at ambient temperature.

PMID- 22614167
TI  - Expression of matrix metalloproteinases 2 and 9 and tissue inhibitors of matrix
      metalloproteinases 2 and 1 in the glomeruli of human glomerular diseases: the
      results of studies using immunofluorescence, in situ hybridization, and
      immunoelectron microscopy.
AB  - BACKGROUND: It has been reported matrix metalloproteinases (MMPs) and their
      inhibitors, tissue inhibitors of matrix metalloproteinases (TIMPs), play
      important roles in the decomposition of the extracellular matrices of the
      glomerulus during the pathological processes in various glomerular diseases.
      Although the activity of these enzymes in cases of experimental
      glomerulonephritis has been described, the expression sites in the glomeruli of
      human renal diseases have been identified in only a few articles and remain
      controversial. METHODS: The expression of the gelatinase group of MMPs (MMP-2 and
      MMP-9) and their inhibitors (TIMP-2 and TIMP-1) were evaluated in 19 renal
      biopsies of several types of glomerular diseases by immunofluorescence (IF)
      labeling. In addition, several samples of immunoglobulin A nephropathy (IgAN)
      were also investigated by in situ hybridization (ISH) and immunoelectron
      microscopy (IEM). RESULTS: The expression of MMP-2 was observed in all the cases
      examined by IF and ISH. TIMP-2 expression varied from negative to positive among
      11 cases of IgAN, but was negative in the cases with lupus nephritis (LN) (n =
      3), membranoproliferative glomerulonephritis (MPGN) (n = 2), and post
      streptococcal glomerulonephritis (n = 1). However, it was weakly positive in the
      cases of diabetic nephropathy (DMN) (n = 2). MMP-2 was mainly observed along
      glomerular capillary loops (GCLs) and Bowman's capsules, whereas TIMP-2 was found
      in the mesangial area. The expression of MMP-9 in cases of IgAN varied, and was
      local, not diffuse, if it was present. MMP-9 expression in cases of LN, MPGN, and
      DMN was diffuse, but the intensity of staining varied. MMP-9 was primarily
      expressed in the mesangium. TIMP-1 expression was negative in all cases except
      for those with IgAN. The localization of MMP-2 in patients with IgAN, which was
      investigated by IEM, was revealed to be mainly on the endothelial cell membranes
      of GCLs, podocyte membranes, the parietal cell membranes of Bowman's capsules,
      and some on the membranes of mesangial cells. CONCLUSION: The study results
      suggest that the expression levels and patterns of MMPs and TIMPs are generally
      similar in several types of glomerular diseases, even though each case has a
      somewhat different distribution and intensity of expression. When these enzymes
      were present, their main sites were as follows: MMP-2 was found along glomerular
      basement membrane, TIMP-2 was located in the acellular mesangial area, MMP-9 was
      seen in the mesangium, and TIMP-1 was hardly detected. MMP-2 expression is
      clearly demonstrated to exist at the above-described sites by IEM in patients
      with IgAN.

PMID- 22614169
TI  - A comparative study of carbonate determination in human teeth using Raman
      spectroscopy.
AB  - Carbonate determination in dental apatites such as dentine and enamel is
      important for studying the dynamics of dental caries and developmental defects of
      these tissues. Traditionally, these determinations have been performed by acidic
      digestion with the subsequent measurement of released carbon dioxide gas. As an
      alternative, Raman spectroscopy has been used for the determination of carbonate
      in synthetic carbonated apatites with at least four analytical methods published
      thus far. However, these methods have not been applied to biological apatites.
      The aim of this comparative study was to test the suitability of these four
      methods for the determination of B-type carbonate in human enamel and dentine. A
      method for determining the A-type carbonate content of enamel using the Raman
      technique is also presented. Raman spectra were obtained from 10 human enamel and
      dentine samples and analysed with each of the four methods using either a single
      or multiple nu(1)(PO(4)(3-)) band spectral fitting model. Each of the methods
      resulted in a different determination for the carbonate content when using the
      same measurement data. The method that used the full-width-at-half-maximum of the
      nu(1)(PO(4)(3-)) band to determine the B-type carbonate concentration was found
      to be in best agreement with (i) the results (using the acid digestion method) of
      teeth collected from the same sample population and (ii) previously reported
      values for both enamel and dentine. The use of a multiple-band spectral fitting
      model produced the highest determination precision (particularly in the case of
      dentine).

PMID- 22614170
TI  - Mindfulness online: a preliminary evaluation of the feasibility of a web-based
      mindfulness course and the impact on stress.
AB  - OBJECTIVES: Stress has been shown to have a number of negative effects on health
      over time. Mindfulness interventions have been shown to decrease perceived stress
      but access to interventions is limited. Therefore, the effectiveness of an online
      mindfulness course for perceived stress was investigated. DESIGN: A preliminary
      evaluation of an online mindfulness course. PARTICIPANTS: This sample consisted
      of 100 self-referrals to the online course. The average age of participants was
      48 years and 74% were women. INTERVENTIONS: The online programme consisted of
      modules taken from Mindfulness Based Stress Reduction and Mindfulness Based
      Cognitive Therapy and lasted for approximately 6 weeks. PRIMARY AND SECONDARY
      OUTCOME MEASURES: Participants completed the Perceived Stress Scale (PSS) before
      the course, after the course and at 1-month follow-up. Completion of formal (eg,
      body scan, mindful movement) and informal (eg, mindful meal, noticing)
      mindfulness activities was self-reported each week. RESULTS: Participation in the
      online mindfulness course significantly reduced perceived stress upon completion
      and remained stable at follow-up. The pre-post effect size was equivalent to
      levels found in other class-based mindfulness programmes. Furthermore, people who
      had higher PSS scores before the course reported engaging in significantly more
      mindfulness practice, which was in turn associated with greater decreases in PSS.
      CONCLUSIONS: Because perceived stress significantly decreased with such limited
      exposure to mindfulness, there are implications for the accessibility of
      mindfulness therapies online. Future research needs to evaluate other health
      outcomes for which face-to-face mindfulness therapies have been shown to help,
      such as anxiety and depressive symptoms.

PMID- 22614172
TI  - Discontinuation of statin therapy in older people: does a cancer diagnosis make a
      difference? An observational cohort study using data linkage.
AB  - OBJECTIVE: The aim was to examine statin discontinuation rates in a cohort of
      elderly Australians with newly diagnosed cancer using population-based secondary
      health data. DESIGN: Observational cohort study. SETTING: New South Wales, the
      largest jurisdiction in Australia. The Pharmaceutical Benefits and Repatriation
      Pharmaceutical Benefits Schemes are national programmes subsidising prescription
      drugs to the Australian population and Australian Government Department of
      Veterans' Affairs clients. PARTICIPANTS: The cohort comprised 1731 cancer
      patients aged >=65 years with evidence of statin use in the 90 days prior to
      diagnosis. They were matched to 3462 non-cancer patients prescribed statins in
      the same period. MAIN OUTCOME MEASURE: The authors compared statin
      discontinuation rates up to 4 years post-diagnosis and examined the factors
      associated with statin discontinuation. RESULTS: The proportion of cancer
      patients discontinuing statin therapy at 4 years (27%) was comparable to the
      comparison cohort; however, significantly higher proportions of the cancer cohort
      discontinued statins than the comparison cohort at 3, 6 and 12 months of follow
      up (9.7% vs 7.4% at 12 months, respectively). More than 30% of cancer patients
      who died were dispensed statins within 30 days of death. Discontinuation of
      statin therapy in cancer patients was associated with regionalised and distant
      disease spread at diagnosis (p<0.001), older age (p=0.006), upper
      gastrointestinal organs and liver cancer (aHR 2.95, 95% CI 1.92 to 4.53) and
      cancer of the lung, bronchus and trachea (aHR 1.99, 95% CI 1.32 to 3.00) and
      poorer survival. CONCLUSIONS: Medications should be rationalised at the time of a
      cancer diagnosis, especially in the setting of a poor prognosis. At least for
      some patients in our cohort, statin therapy may be inappropriately continued
      which adds unnecessarily to therapeutic burden.

PMID- 22614171
TI  - Appetite regulation genes are associated with body mass index in black South
      African adolescents: a genetic association study.
AB  - BACKGROUND: Obesity is a complex trait with both environmental and genetic
      contributors. Genome-wide association studies have identified several variants
      that are robustly associated with obesity and body mass index (BMI), many of
      which are found within genes involved in appetite regulation. Currently, genetic
      association data for obesity are lacking in Africans-a single genome-wide
      association study and a few replication studies have been published in West
      Africa, but none have been performed in a South African population. OBJECTIVE: To
      assess the association of candidate loci with BMI in black South Africans. The
      authors focused on single nucleotide polymorphisms (SNPs) in the FTO, LEP, LEPR,
      MC4R, NPY2R and POMC genes. DESIGN: A genetic association study. PARTICIPANTS:
      990 randomly selected individuals from the larger Birth to Twenty cohort (a
      longitudinal birth cohort study of health and development in Africans). MEASURES:
      The authors genotyped 44 SNPs within the six candidate genes that included known
      BMI-associated SNPs and tagSNPs based on linkage disequilibrium in an African
      population for FTO, LEP and NPY2R. To assess population substructure, the authors
      included 18 ancestry informative markers. Weight, height, sex, sex-specific
      pubertal stage and exact age collected during adolescence (13 years) were used to
      identify loci that predispose to obesity early in life. RESULTS: Sex, sex
      specific pubertal stage and exact age together explain 14.3% of the variation in
      log(BMI) at age 13. After adjustment for these factors, four SNPs were
      individually significantly associated with BMI: FTO rs17817449 (p=0.022), LEP
      rs10954174 (p=0.0004), LEP rs6966536 (p=0.012) and MC4R rs17782313 (p=0.045).
      Together the four SNPs account for 2.1% of the variation in log(BMI). Each risk
      allele was associated with an estimated average increase of 2.5% in BMI.
      CONCLUSIONS: The study highlighted SNPs in FTO and MC4R as potential genetic
      markers of obesity risk in South Africans. The association with two SNPs in the
      3' untranslated region of the LEP gene is novel.

PMID- 22614173
TI  - Palliative care for the management of chronic illness: a systematic review study
      protocol.
AB  - INTRODUCTION: Chronic illnesses are marked by fluctuations and variations over
      time. Individuals with chronic illness experience pain and other symptoms that
      are not always adequately managed. Their caregivers often have to deal with
      enormous burden as the illness progresses. Palliative care can serve as an
      intervention to manage chronic illness, not just at the end of life but also in
      the early phases of illness. METHODS AND ANALYSIS: Randomised and non-randomised
      studies will be included in the systematic review. The focus will be on non
      cancer chronic illness. Sources of data will be from PubMed and other databases
      and will include the reference list of studies included in the systematic review.
      The primary outcome will be to assess the efficacy of palliative care on chronic
      illness. Secondary outcomes will include health-related quality of life, care
      giver burden, quality of care and cost-effectiveness of interventions. The study
      population will consist of patients aged 18 years or over. ETHICS AND
      DISSEMINATION: For purposes of privacy and confidentiality, the systematic review
      will be limited to studies with de-identified data. The systematic review will be
      published in a peer-reviewed journal. It will also be disseminated electronically
      and in print. Brief reports of review findings will be disseminated directly to
      appropriate audiences via email and other modes of communication. Updates of the
      review will be conducted to inform and guide healthcare practice and policy.
      TRIAL REGISTRATION NUMBER: PROSPEROCRD42011001794.

PMID- 22614174
TI  - The International Community-Acquired Pneumonia (CAP) Collaboration Cohort (ICCC)
      study: rationale, design and description of study cohorts and patients.
AB  - OBJECTIVE: To improve the understanding of the determinants of prognosis and
      accurate risk stratification in community-acquired pneumonia (CAP). DESIGN:
      Multicentre collaboration of prospective cohorts. SETTING: 6 cohorts from the
      USA, Canada, Hong Kong and Spain. PARTICIPANTS: From a published meta-analysis of
      risk stratification studies in CAP, the authors identified and pooled individual
      patient-level data from six prospective cohort studies of CAP (three from the
      USA, one each from Canada, Hong Kong and Spain) to create the International CAP
      Collaboration Cohort. Initial essential inclusion criteria of meta-analysis were
      (1) prospective design, (2) in English language, (3) reported 30-day mortality
      and transfer to an intensive or high dependency care and (4) minimum 1000
      participants. Common baseline patient characteristics included demographics,
      history and physical examination findings, comorbidities and laboratory and
      radiographic findings. PRIMARY AND SECONDARY OUTCOME MEASURES: This paper reports
      the rationale, hypotheses and analytical framework and also describes study
      cohorts and patients. The authors aim to (1) compare the prognostic accuracy of
      existing CAP risk stratification tools, (2) assess patient-level determinants of
      prognosis, (3) improve risk stratification by combined use of scoring systems and
      (4) understand prognostic factors for specific patient groups. RESULTS: The six
      cohorts assembled from 1991 to 2007 included 13 784 patients (median age 71
      years, 54% men). Aside from one randomised controlled study, the remaining five
      were cohort studies, but all had similar inclusion criteria. Overall, there was
      0%-6% missing data. A total of 6159 (44%) had severe pneumonia by Pneumonia
      Severity Index class IV/V. Mortality at 30 days was 8% (1036). Admission to
      intensive care or high dependency unit was also 8% (1059). CONCLUSIONS:
      International CAP Collaboration Cohort provides a pooled multicentre data set of
      patients with CAP, which will help us to better understand the prognosis of CAP.

PMID- 22614175
TI  - Senescence is accelerated through donor cell specificity in cloned pigs.
AB  - Animals cloned by somatic cell nuclear transfer (SCNT) sometimes have
      abnormalities that result in large offspring syndrome or early death during
      gestation due to respiratory and metabolic defects. We cloned pigs using two
      sources of donor cells and observed phenotypic anomalies in three pigs cloned
      from one type of cell, s-pig fetal fibroblasts. These animals had many wrinkles
      on their faces and bodies and looked older than age-matched normal pigs. We
      performed the present study to examine whether the wrinkled phenotype in the
      cloned pigs was due to senescence, a genetic problem with donor specificity, or
      epigenetic problems with reprogramming. To address this issue, we investigated
      biomarkers of senescence, including telomere length and the expression of
      senescence-associated beta-galactosidase (SA-beta-gal), glyceraldehyde phosphate
      dehydrogenase (GAPDH) and beta-actin. We also assessed the methylation status of
      euchromatic PRE-1 repetitive sequences and centromeric satellite DNA, and
      measured the mRNA levels of six imprinted genes, Copg2, Mest, Igf2R, GNAS, SNRPN
      and Ube3a. The telomeres of the wrinkled cloned pigs were much shorter than those
      of the normal cloned pigs and age-matched normal pigs. In the wrinkled cloned
      pigs, SA-beta-gal activity was detected and GAPDH and beta-actin were repressed.
      The mRNA levels of Mest, GNAS and Ube3a were reduced in the wrinkled cloned pigs,
      although there was no difference between the normal cloned pigs and normal
      controls. This gene expression analysis indicates that the wrinkled abnormality
      of our pigs originates from genetic abnormalities in the donor cells used for
      SCNT.

PMID- 22614176
TI  - Differential regulation of miR-21 and miR-146a by Epstein-Barr virus-encoded
      EBNA2.
AB  - The discovery of microRNA (miR) represents a novel paradigm in RNA-based
      regulation of gene expression and their dysregulation has become a hallmark of
      many a tumor. In virally associated cancers, the host-pathogen interaction could
      involve alteration in miR expression. Epstein-Barr virus (EBV)-encoded EBNA2 is
      indispensable for the capacity of the virus to transform B cells in vitro. Here,
      we studied how it affects cellular miRs. Extensive miR profiling of the virus
      infected and EBNA2-transfected B lymphoma cells revealed that oncomiR miR-21 is
      positively regulated by this viral protein. Conversely, Burkitt's lymphoma (BL)
      cell lines infected with EBNA2 lacking P3HR1 strain did not show any increase in
      miR-21. EBNA2 increased phosphorylation of AKT and this was directly correlated
      with increased miR-21. In contrast, miR-146a was downregulated by EBNA2 in B
      lymphoma cells. Low miR-146a expression correlates with an elevated level of
      IRAK1 and type I interferon in EBNA2 transfectants. Taken together, the present
      data suggest that EBNA2 might contribute to EBV-induced B-cell transformation by
      altering miR expression and in particular by increasing oncomiR-like miR-21 and
      by affecting the antiviral responses of the innate immune system through
      downregulation of its key regulator miR-146a.

PMID- 22614177
TI  - Targeting the FMS-like tyrosine kinase 3 in acute myeloid leukemia.
AB  - Acute myeloid leukemia (AML) is a highly heterogenous disease with multiple
      signaling pathways contributing to its pathogenesis. A key driver of AML is the
      FMS-like tyrosine kinase receptor-3 (FLT3). Activating mutations in FLT3,
      primarily the FLT3-internal tandem duplication (FLT3-ITD), are associated with
      decreased progression-free and overall survival. Identification of the importance
      of FLT3-ITD and the FLT3 pathway in the prognosis of patients with AML has
      stimulated efforts to develop therapeutic inhibitors of FLT3. Although these
      inhibitors have shown promising antileukemic activity, they have had limited
      efficacy to date as single agents and may require use in combination with
      cytotoxic chemotherapies. Here, we review clinical and preclinical results for
      the clinically mature FLT3 inhibitors currently in development. We conclude that
      multitargeted FLT3 inhibitors may have more utility earlier in the course of
      disease, when in vitro evidence suggests that AML cells are less dependent on
      FLT3 signaling, perhaps because of upregulation of multiple other signaling
      pathways. More potent agents may have greater utility in relapsed and heavily
      pretreated patients, in whom high levels of circulating FLT3 ligand may
      necessitate use of an agent with a very favorable pharmacokinetic/pharmacodynamic
      profile. Novel combination regimens are also discussed.

PMID- 22614178
TI  - Fine mapping and candidate gene analysis of the nuclear restorer gene Rfp for pol
      CMS in rapeseed (Brassica napus L.).
AB  - The Polima (pol) system of cytoplasmic male sterility (CMS) in rapeseed is widely
      used in China for commercial hybrid seed production. Genetic studies have shown
      that its fertility restorer gene (Rfp) is monogenic dominant. For fine mapping of
      the Rfp gene, a near isogenic line comprising 3,662 individuals of BC(14)F(1)
      generation segregating for the Rfp gene was created. Based on the sequences of
      two SCAR markers, SCAP0612ST and SCAP0612EM2, developed by Zhao et al. (Genes
      Genom 30(3):191-196, 2008) and the synteny region of Brassica napus and other
      Brassica species, 13 markers strongly linked with the Rfp gene were identified.
      By integrating three of these markers to the published linkage map, the Rfp gene
      was mapped on linkage group N9 of B. napus. Using these markers, the Rfp locus
      was narrowed down to a 29.2-kb genomic region of Brassica rapa. Seven open
      reading frames (ORFs) were predicted in the target region, of these, ORF2,
      encoding a PPR protein, was the most likely candidate gene of Rfp. These results
      lay a solid foundation for map-based cloning of the Rfp gene and will be helpful
      for marker-assisted selection of elite CMS restorer lines.

PMID- 22614179
TI  - Mapping QTL for agronomic traits in breeding populations.
AB  - Detection of quantitative trait loci (QTL) in breeding populations offers the
      advantage that these QTL are of direct relevance for the improvement of crops via
      knowledge-based breeding. As phenotypic data are routinely generated in breeding
      programs and the costs for genotyping are constantly decreasing, it is tempting
      to exploit this information to unravel the genetic architecture underlying
      important agronomic traits in crops. This review characterizes the germplasm from
      breeding populations available for QTL detection, provides a classification of
      the different QTL mapping approaches that are available, and highlights important
      considerations concerning study design and biometrical models suitable for QTL
      analysis.

PMID- 22614180
TI  - Structure and nuclease resistance of 2',4'-constrained 2'-O-methoxyethyl (cMOE)
      and 2'-O-ethyl (cEt) modified DNAs.
AB  - Combining the structural elements of the second generation 2'-O-methoxyethyl
      (MOE) and locked nucleic acid (LNA) antisense oligonucleotide (AON) modifications
      yielded the highly nuclease resistant 2',4'-constrained MOE and ethyl bicyclic
      nucleic acids (cMOE and cEt BNA, respectively). Crystal structures of DNAs with
      cMOE or cEt BNA residues reveal their conformational preferences. Comparisons
      with MOE and LNA structures allow insights into their favourable properties for
      AON applications.

PMID- 22614181
TI  - Performing cytoreductive nephrectomy following targeted sunitinib therapy for
      metastatic renal cell carcinoma: a surgical perspective.
AB  - OBJECTIVE: To describe for surgeons contemplating performing cytoreductive
      nephrectomy (CRN) on patients after neoadjuvant sunitinib compared to a benchmark
      of open radical nephrectomy, describing technical difficulties, safety and
      feasibility. PATIENTS AND METHODS: We compared measurable surgical parameters and
      perioperative complications in 22 patients with metastatic renal cell carcinoma
      (mRCC) undergoing CRN after neoadjuvant sunitinib, with 28 patients who underwent
      open radical nephrectomy for non-metastatic disease (nmRCC). RESULTS: Median
      blood loss (320 vs. 775 ml), median operative time (128 vs. 195 min) and median
      length of stay (5 vs. 7 days) were greater in the mRCC group. Surgery after
      sunitinib was technically challenging due to fibrosis, loss of the tissue planes
      that usually facilitate radical nephrectomy and abnormal blood vessel formation.
      Side effects of sunitinib resulted in predictable complications. CONCLUSION: CRN
      after treatment with sunitinib is safe and feasible in our hands, although the
      surgery is more time-consuming and technically demanding. A multidisciplinary
      approach is mandatory.

PMID- 22614183
TI  - First experience with proteasome inhibitor treatment of radioiodine nonavid
      thyroid cancer using bortezomib.
AB  - PURPOSE: Radioiodine nonavid thyroid cancer (TC) is a rare disease entity with a
      poor prognosis. Despite a multimodal therapeutic approach including surgery,
      chemotherapy, and external beam radiation, radioiodine nonavid TC accounts for a
      high number of TC-associated deaths. The aim of this investigation was to
      evaluate the response rate of progressive TC patients to treatment with the
      proteasome inhibitor bortezomib. MATERIALS AND METHODS: Seven patients with
      inoperable, metastasized progressive TC proven to be radioiodine nonavid were
      included into this pilot study. Patients received bortezomib intravenously with a
      standardized dose of 1.3 mg/m on days 1, 4, 8, and 11. All patients underwent 3
      therapeutic cycles with an interval of 10 days. [F]2-deoxy-2-fluoro-D-glucose
      positron emission tomography (F-FDG PET) and measurements of thyroglobulin levels
      were performed before, during, and after therapy, with a 6-week interval to post
      therapeutic follow-up. RESULTS: Stable disease was seen after proteasome
      inhibitor therapy in 4 of the 7 patients. Two of the 7 patients showed decrease
      of maximum standardized uptake value in both post-therapeutic follow-up
      investigations, and one of these cases also had decreasing thyroglobulin levels.
      Two patients experienced stable disease during the posttherapeutic follow-up. Two
      patients showing a mixed response had an improvement in their clinical situation.
      One patient had rapidly progressive disease, and died 3 months after the last
      therapeutic cycle. Adverse events included mild polyneuropathy in 2 patients and
      alterations of the blood count up to WHO (World Health Organization) grade 2 in 5
      patients. CONCLUSION: Proteasome inhibitor treatment with bortezomib is a
      promising therapeutic approach in TC patients without an established treatment
      alternative. The development of a specific therapeutic regimen for the treatment
      of radioiodine nonavid TC is warranted.

PMID- 22614182
TI  - Variations in soil culturable bacteria communities and biochemical
      characteristics in the Dongkemadi glacier forefield along a chronosequence.
AB  - The variations in the soil culturable bacterial communities and biochemical
      parameters of early successional soils from a receding glacier in the Tanggula
      Mountain were investigated. We examined low organic carbon (C) and nitrogen (N)
      contents and enzymatic activity, correlated with fewer bacterial groups and
      numbers in the glacier forefield soils. The soil pH values decreased, but the
      soil water content, organic C and total N significantly increased, along the
      chronosequence. The soil C/N ratio decreased in the early development soils and
      increased in the late development soils and it did not correlate with the soil
      age since deglaciation. The activities of soil urease, sucrase, protease,
      polyphenol oxidase, catalase, and dehydrogenase increased along the
      chronosequence. The numbers of culturable bacteria in the soils increased as
      cultured at 25 degrees C while decreased at 4 degrees C from younger soils to
      older soils. Total numbers of culturable bacteria in the soils cultured at 25
      degrees C were significantly positively correlated to the soil total N, organic
      C, and soil water content, as well as the activities of soil urease, sucrase,
      dehydrogenase, catalase, and polyphenol oxidase. We have obtained 224 isolates
      from the glacier forefield soils. The isolates were clustered into 28 groups by
      amplified ribosomal DNA restriction analysis (ARDRA). Among them, 27 groups and
      25 groups were obtained from the soils at 25 degrees C and at 4 degrees C
      incubation temperatures, respectively. These groups are affiliated with 18 genera
      that belong to six taxa, viz, Actinobacteria, Gammaproteobacteria, Bacteroidetes,
      Firmicutes, Alphaproteobacteria, and Betaproteobacteria. The dominant taxa were
      Actinobacteria, Gammaproteobacteria, and Bacteroidetes in all the samples. The
      abundance and the diversity of the genera isolated at 25 degrees C incubation
      temperature were greater than that at 4 degrees C.

PMID- 22614184
TI  - Preablation stimulated thyroglobulin is a good predictor of successful ablation
      in patients with differentiated thyroid cancer.
AB  - PURPOSE: To evaluate the predictive capacity of clinical and laboratory variables
      in relation to the success of ablation. The variables studied were as follows:
      thyroglobulin (Tg) in hypothyroidism, before ablation; age; gender; type of
      carcinoma (papillary or follicular); the tumor stage; the administered activity
      of I; and the whole-body scan 7 days after ablation. MATERIALS AND METHODS:
      Retrospective review of the medical records of all patients who were admitted to
      the therapeutic room to undergo treatment with I, from 1998 to 2007. Of the
      records reviewed, 96 patients fulfilled the inclusion criteria and had no
      exclusion criteria. A negative whole-body scan and Tg in hypothyroidism <2 ng/mL,
      after 6 to 12 months of treatment, were considered as successful ablation.
      RESULTS: The dosage of Tg in hypothyroidism, measured before the ablation, was
      the only independent predictor of ablation success in multivariate analysis (P <
      0.0001), and the optimal cutoff for this cohort was 18 ng/mL. On univariate
      analysis, the high-risk staging was predictor of ablation failure. CONCLUSION:
      The measurement of Tg in hypothyroidism before ablation might be useful if added
      to the routine evaluation of patients before I treatment because it was a good
      predictor of successful ablation.

PMID- 22614185
TI  - Predictive factors of failure in a fixed 15 mCi 131I-iodide therapy for Graves'
      disease.
AB  - PURPOSE: To investigate the factors influencing the success rate in a fixed, 15
      mCi approach for treatment of Graves' hyperthyroidism. MATERIAL AND METHODS: The
      thyroid function outcome (hyperthyroidism or euthyroidism/hypothyroidism) was
      verified at least 1 year after radioiodine therapy (RIT) retrospectively and
      compared with presenting clinical characteristics and pre-RIT parameters in 87
      patients treated with I-iodide for Graves' disease in a tertiary care center.
      RESULTS: After RIT, 16 patients (18.4%) became euthyroid, 54 patients (62.1%)
      became hypothyroid, and 17 (19.5%) remained hyperthyroid. We found no
      statistically significant association between thyroid function outcome and gender
      (P = 0.50), ophthalmopathy (P = 0.69), drug used (methimazole or
      propylthiouracil; P = 1.00), maintenance or withdrawal of thionamides pre-RIT (P
      = 0.98), or 99mTc sodium pertechnetate thyroid uptake prior to RIT (P = 0.75).
      The only variable associated with the success rate was thyroid mass <62 g (P <
      0.001). CONCLUSIONS: Our study has shown that a fixed 15 mCi approach for
      treatment of Graves' disease was effective, but high failure rates were observed
      in patients presenting larger goiters, particularly those with estimated thyroid
      mass >62 g.

PMID- 22614186
TI  - 131I SPECT/CT in the follow-up of patients with differentiated thyroid carcinoma.
AB  - PURPOSE: 131I SPECT/Spiral-CT has been shown to be superior to planar imaging in
      staging of differentiated thyroid carcinoma (DTC) at first radioablation. The
      purpose of this study was to investigate whether this is also true in the further
      follow-up of patients with DTC. METHODS: From our clinical database, all patients
      with DTC who underwent planar scintigraphy as well as SPECT/low-dose spiral CT
      during follow-up between June 2005 and August 2010 were selected. Iodine-positive
      foci on the planar images as well as on the SPECT/CT data sets were classified as
      benign or equivocal/malignant. The criterion standard was provided by histology,
      other imaging modalities, and clinical and serological follow-up of at least 6
      months. RESULTS: A total of 123 patients with altogether 139 studies met the
      selection criteria. Whereas the sensitivities of SPECT/CT and planar imaging did
      not differ significantly (both 62%), the specificity of SPECT/CT was
      significantly higher than that of planar imaging (98 vs 78%, P < 0.01). SPECT/CT
      yielded a gain in diagnostic information in 20 (16.3%) of 123 patients (95%
      confidence interval, 10.8%-23.8%). Hybrid imaging led to a change of diagnosis in
      none of the patients in whom planar imaging result was normal, in 16% of patients
      with foci in the neck, and in 26% of patients with extracervical foci.
      CONCLUSIONS: In the follow-up of patients with DTC, SPECT/CT significantly
      improves specificity compared with planar imaging. Incremental diagnostic value
      is higher in lesions outside the neck than in those in the neck and absent in
      patients without iodine-positive foci on planar imaging.

PMID- 22614187
TI  - Detection of subcentimeter metastatic cervical lymph node by 18F-FDG PET/CT in
      patients with well-differentiated thyroid carcinoma and high serum thyroglobulin
      but negative 131I whole-body scan.
AB  - PURPOSE: This study aimed to evaluate the diagnostic value of 18F-FDG PET/CT and
      identify the best parameter to detect subcentimeter cervical nodal metastasis in
      patients with a well-differentiated thyroid carcinoma (WDTC), elevated serum
      thyroglobulin (Tg) levels, but negative findings in the 131I whole-body scan
      (WBS). MATERIALS AND METHODS: We prospectively studied 30 consecutive patients
      with WDTC after standard surgery and radioiodine treatment. All patients had
      serum Tg greater than 10 ng/mL during thyroid hormone withdrawal but negative
      findings in the therapeutic 131I WBS. One whole-body CT scan and serial whole
      body and neck PET scans were performed between 10 and 170 minutes after 18F-FDG
      injection. Parameters studied were SUVmax, percent change in SUVmax, SUV ratios
      of lesions to reference organs, and their percent change. Result in the PET/CT
      scan was correlated with histopathology and follow-up information. Patient-based
      and lesion-based (subcentimeter cervical lymph nodes) analyses were performed.
      Outcome of Tg level after lymph node resection was also analyzed. RESULTS: The
      overall sensitivity, specificity, accuracy, and positive and negative predictive
      values were 100%, 78%, 93%, 91%, and 100%, respectively. In lesion-based
      analysis, the differential SUVmax between 2 time points did not provide higher
      sensitivity than the individual SUVmax at the 60th or 90th minute. A combined
      SUVmax at the 90th minute greater than 2.75 and a percent change of SUVmax
      between the 60th and 90th minute greater than -1.1% provides the best diagnostic
      value with sensitivity, specificity, accuracy, and positive and negative
      predictive values of 81%, 90%, 83%, 97%, and 56%, respectively. After surgery,
      patients with completely resected PET-positive nodes without distant metastasis
      showed reduction of suppressed Tg to less than 2 ng/mL. CONCLUSIONS: Combined
      SUVmax at the 90th minute and the percent change of SUVmax between the 60th and
      90th minute provides the best diagnostic value to differentiate benign from
      malignant conditions in subcentimeter lymph nodes.

PMID- 22614188
TI  - Parathyroid scintigraphy: when, how, and why? A concise systematic review.
AB  - In recent years, preoperative imaging has become essential in the evaluation of
      sporadic primary hyperparathyroidism (HPT) for selecting good candidates for
      minimally invasive HPT. Its role in patients with secondary/tertiary HPT is under
      investigation. Imaging is mandatory before reoperative parathyroid surgery for
      persistent or recurrent HPT, whatever the setting. This review provides detailed
      information regarding the nuclear imaging methods (dual phase, subtraction), the
      role of SPECT and SPECT/CT, and the clinical results of parathyroid scintigraphy
      in different clinical situations.

PMID- 22614189
TI  - Skeletal muscle metastases on FDG PET/CT imaging.
AB  - BACKGROUND: Skeletal muscle metastases (SMM) are a rare occurrence despite the
      fact that skeletal muscle comprises more than 50% of total body mass. When
      present, most are asymptomatic and are often found incidentally on imaging.
      Several studies have reported isolated cases of patients with SMM. The goal of
      our study was to perform a comprehensive retrospective analysis of the incidence,
      frequency, and source of SMM in patients with malignancies who underwent whole
      body FDG PET/CT imaging for the workup for their malignancy. METHODS: The records
      of 8492 consecutive patients referred for oncologic imaging at our institution
      during the period from January 2006 to December 2009 were reviewed. Patients who
      had SMM on FDG PET imaging were further assessed for collaborating evidence on
      other imaging modalities, pathology from tissue sampling, and follow-up scans.
      The incidence of SMM in our setting was calculated, and their association with
      various primary malignancies was also evaluated. RESULTS: A total of 73 patients
      with SMM were identified on PET/CT imaging (incidence, 0.86%). Lung cancer was
      the most frequent source (25 patients [34%]), followed by gastrointestinal tract
      malignancies (13 patients [18%]), breast cancer (10 patients [14%]),
      genitourinary malignancies and lymphoma (6 patients [8%] each), melanoma (5
      patients [7%]), and other miscellaneous malignancies (3 patients [4%]). Primary
      source remained unknown in only 5 patients (7%). Most patients with SMM generally
      had markedly widespread involvement which led to an unusual appearance on FDG
      PET/CT imaging. However, since most of these patients had stage IV malignant
      disease by virtue of visceral metastases elsewhere as well, they were generally
      not upstaged. CONCLUSIONS: Our study confirmed the rare occurrence of SMM.
      Furthermore, FDG PET/CT can potentially detect unsuspected SMM. Interestingly, in
      our patient population, lung cancer was found to be the most frequent malignancy
      metastasizing to the skeletal muscles. Knowledge about the presence and
      appearance of widespread SMM may aid in appropriate interpretation of FDG PET/CT
      scans.

PMID- 22614190
TI  - Communicating in organizations, Part IV: E-mails and one-on-one meetings.
AB  - E-mail messages and face-to-face meetings both are important methods of
      communication, and each has its own advantages and disadvantages. Conducting
      informal one-on-one meetings well is important to the success of a leader or
      manager. However, the follower can also do many things to optimize the success of
      a one-on-one discussion with his superior.

PMID- 22614191
TI  - The role of 99mTc-tetrofosmin brain SPECT in intracranial meningiomas.

PMID- 22614192
TI  - Endogenous thyroid-stimulating hormone and radioactive iodine uptake in normal
      subjects.
AB  - In 105 normal volunteers, 52 male and 53 female, mean age 45 (range, 20-68),
      serum thyroid-stimulating hormone (TSH) (1.46 +/- 0.7; range, 0.43-3.87
      microUI/mL) and 24-hour thyroid radioactive iodine uptake (RAIU) (16.15% +/-
      4.78% range, 6.45%-30.08%) were measured. Additionally, TSH was 1.18 +/- 0.5
      microUI/mL for 20 to 29 year-olds and 1.59 +/- 0.9 microUI/mL for 60 to 68 year
      old (P = 0.037). RAIU was 18.30 +/- 4.5 for 20 to 29-year-olds and 14.92 +/- 3.1
      for 60 to 68 year-olds (P = 0.009). TSH trends positively and RAIU at 24 hours
      correlates negatively with aging of the pituitary axis.

PMID- 22614193
TI  - Thoracic 131I uptake after previous pneumonectomy in patients treated for
      differentiated thyroid cancer.
AB  - In patients treated for differentiated thyroid cancer with radioiodine (131I),
      abnormal uptake on post-therapeutic whole-body scan may lead to repeated
      administration of 131I. Uptake not linked to thyroid cancer but to other
      conditions should be recognized so that patients are not overtreated. We describe
      3 cases of unilateral thoracic 131I uptake in patients previously treated by
      pneumonectomy for lung cancer, without evidence of persistent lung cancer.

PMID- 22614194
TI  - 68Ga DOTANOC PET/CT detects medullary thyroid cancer relapse at bone level.
AB  - A patient with a history of radical thyroidectomy for medullary thyroid carcinoma
      (MTC) was studied by 68Ga [DOTA,1-Nal3]octreotide PET/CT for suspected relapse.
      PET/CT documented a focal area of somatostatin receptors expression at bone
      level. Although 68Ga DOTA-peptides PET has been successfully used for the
      detection of neuroendocrine tumors, its role in MTC patients is still under
      evaluation. In fact, although deriving from the neural crest, MTC cells may show
      a variable expression of somatostatin receptors. This case shows that PET/CT with
      DOTANOC may be a useful complementary imaging modality in patients with well
      differentiated MTC.

PMID- 22614195
TI  - Incidental finding of parathyroid adenoma with 11C-choline PET/CT.
AB  - Positron emission tomography/computed tomography (PET/CT) with 11C-choline is an
      established diagnostic tool for restaging prostate cancer patients with
      biochemical failure after primary treatment. In the present case, 11C-choline
      PET/CT was performed in a prostate cancer patient with skeletal metastases,
      treated with hormonal therapy. In addition to the detection of pathologic uptake
      at prostate and vertebra, 11C-choline uptake occurred in the neck. The finding
      was suggestive for a parathyroid adenoma on subsequent ultrasound, then finally
      confirmed by parathyroid scintigraphy and histopathological analysis performed
      after hemithyroidectomy.

PMID- 22614196
TI  - Pheochromocytoma in multiple endocrine neoplasia type 2A: positive 123I MIBG with
      negative CT and equivocal 131I MIBG imaging.
AB  - An 123I metaiodobenzylguanidine (MIBG) planar image showed abnormal uptake in the
      left adrenal gland and thyroid in a 24-year-old woman with multiple endocrine
      neoplasia type 2A. 131I MIBG showed abnormal uptake in the thyroid but not in the
      adrenal gland. Abdominal CT with 2-mm thin slices demonstrated a normal adrenal
      gland. Postoperative pathologic findings were consistent with medullary carcinoma
      in both thyroid lobes and a small 1-mm pheochromocytoma in the left adrenal
      gland. 123I MIBG could clearly show the small pheochromocytoma, which was
      negative in thin-slice CT and equivocal in 131I MIBG.

PMID- 22614197
TI  - Multimodality evaluation of cardiac paraganglioma.
AB  - We report 2 rare cases of primary cardiac paraganglioma demonstrated with
      multimodality imaging. Both a 46-year-old woman who presented with hypertension
      (case 1) and a 46-year-old woman without any symptoms (case 2) had mediastinal
      tumors depicted by CT and MRI. Both cases showed intense focal uptakes in the
      tumors with iodine-123-meta-iodobenzylguanidine SPECT. Case 2 also underwent 18F
      FDG PET/CT and revealed a focal uptake. CT angiography detected the arterial
      feeder and venous drainages, information that was useful for the operation. After
      surgical removal, pathology confirmed primary cardiac paraganglioma in both
      cases. 18F-FDG PET/CT was also useful in ruling out residual or recurrent tumors.

PMID- 22614198
TI  - Hybrid SPECT/CT evaluation of dual ectopia of thyroid in the absence of
      orthotopic thyroid gland.
AB  - Ectopic thyroid tissue (ETT) refers to all cases in which the thyroid gland is
      present at a location other than its usual site. The prevalence of ETT is
      approximately 1 per 100,000 to 300,000 persons and is reported to occur in 1 of
      4000 to 8000 patients with thyroid disease. Multiple ectopia of the thyroid is
      extremely rare, with fewer than 35 cases published in literature to date. We
      report a 4-year-old girl with euthyroid and dual ectopia of thyroid without
      orthotopic thyroid gland. The role of hybrid SPECT/CT in the localization of the
      sites of ETT is also highlighted.

PMID- 22614199
TI  - 99mTc pertechnetate thyroid scan leads to serendipitous detection of metastatic
      thyroid cancer.
AB  - 99mTc pertechnetate is considered insensitive in detecting thyroid carcinoma
      metastases. We report the case of a 71-year-old male patient, in whom metastasis
      of an unknown thyroid cancer was diagnosed incidentally on a routine 99mTc
      pertechnetate scan, performed for the assessment of nodular thyroid disease.
      Marked tracer accumulation was unexpectedly noted on the left frontal region,
      where a palpable, painless, soft tissue mass was present. Surgical excision of
      the mass revealed metastatic poorly differentiated thyroid carcinoma synchronous
      to soft tissue and adjacent bone.

PMID- 22614200
TI  - High FDG and low FLT uptake in a thyroid papillary carcinoma incidentally
      discovered by FDG PET/CT.
AB  - We report a 58-year-old man whose incidentally discovered papillary thyroid
      carcinoma in the left lobe showed high FDG and low FLT uptake on PET/CT. The
      SUVmax was 19.7 for FDG and 3.0 for FLT. The Ki-67 labeling index of the tumor
      was 1.9%. Thus, the low FLT uptake might be attributed to the low proliferative
      activity of this cancer.

PMID- 22614201
TI  - Simultaneous dacryocystography and dacryoscintigraphy using SPECT/CT in the
      diagnosis of nasolacrimal duct obstruction.
AB  - Epiphora, an abnormal overflow of tears, is commonly caused by tear drainage
      system anomalies including nasolacrimal duct obstruction. To assess morphologic
      abnormalities, dacryocystography by CT is used when CT contrast material is
      syringed into the lacrimal drainage system. To evaluate the function of the
      system, dacryoscintigraphy is the most readily available noninvasive method. In
      the case presented, a 43-year-old man was referred to our clinic with an 8
      months' history of indefinite left side epiphora. After performing
      dacryoscintigraphy, we acquired SPECT/CT images during dacryocystography by CT to
      establish the surgical indication.

PMID- 22614202
TI  - Absence of urine production due to renal failure enables clear visualization of
      primary urinary bladder carcinoma on 18F-FDG PET/CT.
AB  - An 81-year-old man affected by renal failure, underwent 18F-FDG PET/CT for
      detecting primary lesion because of multiple lung nodules consistent with
      secondary lesions revealed by computed tomography without contrast. PET study
      documented high pathologic uptake at anterior and upper wall of urinary bladder,
      and a primary urinary bladder cancer was suspected. Biopsy confirmed the presence
      of a high-grade transitional cell carcinoma.

PMID- 22614203
TI  - A case of gouty arthritis to tophi on 18F-FDG PET/CT imaging.
AB  - We report a case of gouty arthritis with tophi that was evaluated using 18F
      fluorodeoxyglucose (FDG) positron emission tomography. A 77-year-old man with a
      history of gouty attacks was admitted with severe polyarticular pain and fever.
      18F-FDG positron emission tomography/CT demonstrated focal uptake at multiple
      joints, including the juxta-articular soft-tissue-density masses of the elbows,
      and the bases of bilateral large toes. Gouty arthritis should be considered with
      focal 18F-FDG uptake in juxta-articular soft-tissue-density masses (tophi) with
      or without associated erosions.

PMID- 22614204
TI  - Infection of pancreatic pseudocyst demonstrated on PET/CT using 18F
      fluorodeoxyglucose-labeled autologous leucocytes.
AB  - Labeled leukocyte scintigraphy has been used as an indicator of pancreatic
      necrosis in patients with acute pancreatitis and proposed for the detection of
      infection in peripancreatic fluid collections. The authors present a PET/CT scan
      showing abnormal uptake of 18F-Fluorodeoxyglucose-labeled autologous leukocytes
      in a pancreatic pseudocyst, from which aspirated fluid subsequently showed growth
      of Pseudomonas aeruginosa.

PMID- 22614205
TI  - Significant head motion can cause either hypermetabolic or hypometabolic cerebral
      activity on 18F-FDG PET/CT.
AB  - We report 2 separate cases with significant head motion causing apparent
      hypometabolic and hypermetabolic cerebral activity on FDG PET/CT. Case 1 is a 57
      year-old man with facial numbness status post chemotherapy for mantle cell
      lymphoma. Restaging attenuation-corrected PET showed increased left frontal
      region activity, whereas nonattenuation-corrected PET demonstrated evidence of
      patient motion with normal physiologic left frontal cortical activity. Case 2 is
      a 78-year-old man with history of malignant melanoma. Attenuation-corrected
      PET/CT demonstrated diffusely decreased activity in the left cerebral hemisphere,
      whereas nonattenuation-corrected PET showed significant head motion with intact
      cortical activity.

PMID- 22614206
TI  - Patellar metastasis from lung adenocarcinoma revealed by FDG PET/CT.
AB  - We report a case of a 57-year-old woman with lung adenocarcinoma, who presented
      with right knee pain, swelling, and erythema. The initial [18F]-2
      fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT)
      scan performed for staging purposes showed a right patellar metastasis,
      subsequently confirmed by pathology. After administration of systemic
      chemotherapy supplemented by local radiation therapy to the right patella, a
      follow-up FDG PET/CT scan revealed a grossly stable right patellar lesion. The
      patient underwent right patellectomy with reconstruction of the extensor
      mechanism. A subsequent FDG PET/CT scan showed postoperative changes, with no
      evidence of residual malignancy in the right knee region.

PMID- 22614207
TI  - Pericatheter leak in a peritoneal dialysis patient: SPECT/CT diagnosis.
AB  - A 62-year-old patient with end-stage renal disease who is managed with continuous
      ambulatory peritoneal dialysis developed anterior abdominal wall swelling and
      pain that extended from just above peritoneal catheter site caudally. CT of the
      abdomen suggested pericatheter abscess with panniculitis. Tc-99m sulfur colloid
      peritoneal distribution planar scintigraphy suggested the diagnoses of
      pericatheter leak. The addition of SPECT/CT confirmed the latter diagnosis and
      pinpointed the exact location of the peritoneal leakage that was around insertion
      site. SPECT/CT was useful in establishing unequivocal diagnosis of peritoneal
      leak.

PMID- 22614208
TI  - Ipilimumab-induced colitis on FDG PET/CT.
AB  - A 52-year-old woman with metastatic melanoma was treated with ipilimumab. After 2
      cycles of treatment, she developed watery diarrhea, sweats, and chills. An FDG
      PET/CT study demonstrated new FDG-avid (maximum standardized uptake value 15.6)
      diffuse colonic wall thickening, suggestive of ipilimumab-induced colitis. The
      patient was treated with systemic steroids, with subsequent resolution of her
      symptoms. Based on the response to steroids, the diagnosis of ipilimumab-induced
      enterocolitis was made. Ipilimumab may cause several immune-mediated toxicities,
      the most common of which is enterocolitis. Physicians interpreting FDG PET/CT
      examinations of patients treated with ipilimumab should be aware of these FDG
      avid immune-mediated toxicities.

PMID- 22614209
TI  - Current readings.

PMID- 22614210
TI  - Percutaneous osteoplasty combined with radioiodine therapy as a treatment for
      bone metastasis developing after differentiated thyroid carcinoma.
AB  - BACKGROUND: Bone metastasis developing after differentiated thyroid carcinoma
      (DTC) is common, and in most cases, this condition leads to osteolysis. However,
      treatment of bone metastases in DTC patients is a great challenge. The purpose of
      this study was to evaluate the effectiveness of percutaneous osteoplasty (POP)
      combined with radioiodine therapy for treating bone metastasis developing after
      DTC. PATIENTS AND METHODS: We retrospectively studied 8 patients who had
      undergone POP combined with radioiodine therapy for bone metastases after DTC.
      All patients underwent total thyroidectomy and were administered an oral dose of
      131I (3.7 GBq, 100 mCi) for ablation of the residual thyroid. Thereafter, a POP
      was performed at 2 to 3 months followed by 2 to 5 sessions of radioiodine therapy
      every 4 to 6 months after the first 131I therapy. The therapeutic effectiveness
      of this treatment was evaluated on the basis of the changes in serum
      thyroglobulin (Tg) level and imaging characteristics, palliation of bone pain,
      and alleviation of neurologic symptoms. RESULTS: After POP, the mean serum Tg
      level decreased by 86.0% (range, 68.1%-99.3%). The mean serum Tg level markedly
      declined further by 67.4% (range, 37.1%-90.2%) after repeated radioiodine
      therapy. All the patients experienced immediate and substantial alleviation of
      bone pain and neurologic symptoms, and their quality of life markedly improved.
      The bone-destructive lesions were filled with bone cement to enhance skeletal
      stability. No severe complications developed. CONCLUSION: POP, a minimally
      invasive procedure, combined with radioiodine therapy seems to be highly
      effective in providing pain relief and bone stability and in improving the
      quality of life of DTC patients with bone metastases. After POP, radioiodine
      therapy is essential.

PMID- 22614211
TI  - A stepwise approach using metabolic volume and SUVmax to differentiate malignancy
      and dysplasia from benign colonic uptakes on 18F-FDG PET/CT.
AB  - PURPOSE: The purpose of this study was to suggest a new diagnostic strategy using
      metabolic volume (MV) and maximum standardized uptake value (SUVmax) to
      differentiate malignancy and dysplasia from benign colonic 2-deoxy-2-18F-fluoro-D
      glucose (FDG) uptakes. MATERIALS AND METHODS: From records of 21,317 consecutive
      FDG positron emission tomography/computed tomography (PET/CT) scans at 2 centers,
      102 focal colonic lesions in 99 patients investigated by colonoscopy and
      histopathologic examination were eligible for this retrospective study. SUVmax
      and MV were compared according to colonoscopic and histopathologic results.
      Firstly, dysplasia was separated from malignancy and benign lesions. Secondly,
      malignancy and benign lesions were separated from each other. The better
      parameters of each step were determined, and a diagnostic strategy was developed
      from their combination. RESULTS: A total of 102 incidental colonic FDG uptakes
      were revealed as 32 malignancies, 43 dysplasias, and 27 benign lesions. MV better
      differentiated dysplasia from malignancy and benign lesions (cutoff value, <=3.14
      cm3; area under the receiver-operating characteristic curve [AUC] = 0.947), and
      SUVmax better differentiated malignancy from benign lesions (cutoff value, >9.1;
      AUC = 0.934). Overall, the stepwise algorithm using MV and SUVmax (AUC = 0.886)
      was superior to single measurements of SUVmax (AUC = 0.750) and MV (AUC = 0.714)
      for differentiating malignancy and dysplasia from benign lesions; sensitivity:
      92%, specificity: 85%, accuracy: 90%, positive predictive value: 94%, negative
      predictive value: 79%. CONCLUSIONS: The stepwise approach using MV and SUVmax was
      able to differentiate malignancy and dysplasia from benign colonic FDG uptakes on
      PET/CT. Colonic FDG uptake with MV <=3.14 cm3 had a high probability of
      dysplasia. MV >3.14 cm3 and SUVmax >9.1 indicated malignancy, whereas MV >3.14
      cm3 and SUVmax <=9.1 indicated benign lesions.

PMID- 22614212
TI  - Does the pretherapeutic tumor SUV in 68Ga DOTATOC PET predict the absorbed dose
      of 177Lu octreotate?
AB  - PURPOSE: Selection of candidates for peptide receptor radionuclide therapy (PRRT)
      is increasingly based on receptor positron emission tomography (PET) imaging,
      including the common tracer 68Ga DOTATOC. However, no studies have yet compared
      standardized uptake values (SUVs) and absorbed doses in this field. MATERIALS AND
      METHODS: We retrospectively analyzed a consecutive cohort of 21 patients with 61
      evaluable tumor lesions undergoing both pretherapeutic 68Ga DOTATOC-PET/CT
      (Biograph Duo [Siemens Medical Solutions, Erlangen, Germany]; PET acquisition,
      75.3 +/- 15.4 minutes postinjection; 117.3 +/- 33.9 MBq 68Ga DOTATOC) and PRRT
      with Lu octreotate (7.47 +/- 1.39 GBq; intratherapeutic tumor dosimetry with
      serial whole-body scans; 1, 2, and 4 days postinjection) at our institution. SUVs
      were compared with the tumor-absorbed doses per injected activity (D/A0) of the
      subsequent first treatment cycle. RESULTS: The correlation of SUV and D/A0 was r
      = 0.72 (SUVmean) and r = 0.71 (SUVmax), both P < 0.001. Pancreatic origin and
      hepatic localization were associated with higher D/A0, and chromogranin A level
      and Ki-67 index had no influence on SUV or D/A0. High-SUV lesions (SUVmean >15;
      SUVmax >25) resulted in high D/A0 (>10 Gy/GBq) in 66.7% to 70.8% and low D/A0 (<5
      Gy/GBq) in only 8.3% to 12.5% on subsequent PRRT. The mentioned low D/A0 range,
      on the other hand, was achieved by all lesions with SUVmean <7 or SUVmax <9.
      CONCLUSIONS: Somatostatin receptor PET imaging may predict tumor-absorbed doses.
      The ability to indicate insufficient target irradiation by a low SUV could aid in
      selection of appropriate candidates for PRRT. However, larger series are needed
      to confirm and validate these initial findings.

PMID- 22614213
TI  - A rare case of malignant urinary bladder paraganglioma with distant metastases
      demonstrated by 18F-FDG PET/CT.
AB  - Urinary bladder paragangliomas are rare tumors, with malignant ones being still
      rarer. Demonstration of metastases by imaging is crucial, as histological
      examination of primary cannot reliably distinguish between benign and malignant
      tumors. We describe a rare case of a patient with malignant urinary bladder
      paraganglioma in whom 18F-FDG PET/CT was useful in detection of regional lymph
      nodal and distant metastases. In addition, 18F-FDG PET/CT suggested an easily
      accessible site of biopsy to confirm the metastatic disease.

PMID- 22614214
TI  - Cosmetic-related changes on 18F-FDG PET/CT.
AB  - We present 4 cases of cosmetic-related changes on 18F-FDG PET/CT. These cases
      represent post-treatment changes from facial juvederm injection, silicone
      injection in the chest wall and gluteal areas, paraffin injection in the gluteal
      region, and liposuction. Recognition of cosmetic-related changes and their
      appearance on PET and CT will help to avoid potential false-positive
      interpretations.

PMID- 22614215
TI  - F-18 FDG uptake in a retroperitoneal cystic lymphangioma mimicking malignancy.
AB  - Retroperitoneal lymphangiomas are rare benign cystic tumors and occur because of
      failure of the developing lymphatic tissue to establish normal communication with
      the remainder of the lymphatic system. We present a case of retroperitoneal
      cystic lymphangioma that mimicked malignancy on FDG PET-CT. Inhomogeneous FDG
      accumulation was found in this multicystic tumor. Histopathologic findings
      suggested that lymphocytes in the fibrous septa may contribute to FDG uptake of
      this retroperitoneal cystic lymphangioma.

PMID- 22614216
TI  - Multimodality imaging of fat-containing adrenal metastasis from hepatocellular
      carcinoma.
AB  - A biopsy-proven fat-containing metastasis to the adrenal gland in a patient with
      hepatocellular carcinoma demonstrated low density on nonenhanced CT,
      heterogeneity on contrast-enhanced CT, and marked signal loss on opposed-phase
      gradient-echo MRI, mimicking an adrenal adenoma. However, the mass was not
      present on older studies and showed increased FDG uptake on PET. The possibility
      of a fat-containing metastasis should be considered for an apparent adrenal
      adenoma in a patient with a primary hepatocellular carcinoma.

PMID- 22614217
TI  - Detection of intraluminal tracheal metastasis of thyroid papillary carcinoma by
      18F-FDG PET/CT.
AB  - We present a case of a 66-year-old female patient with thyroid papillary
      carcinoma. On the fluorine-18 fluorodeoxyglucose (F18-FDG) positron emission
      tomography/computed tomography (PET/CT) performed for thyroglobulin elevation
      accompanied by negative radioiodine whole-body scan, there was an intense 18F-FDG
      uptake in the polypoid soft tissue invading the tracheal cartilage and extending
      into the lumen. Dedifferentiated tumor with high metabolic rate can be easily
      detected by 18F-FDG PET/CT.

PMID- 22614219
TI  - Thyroid involvement in ankylosing spondylitis and relationship of thyroid
      dysfunction with anti-TNF alpha treatment.
AB  - Association between rheumatological and autoimmune thyroid disorders has been
      demonstrated by many studies. However, a few data exist indicating the
      association between thyroid disorders and ankylosing spondylitis (AS). In this
      study, the frequency of thyroid disorders in patients with AS and the impact of
      anti-TNF alpha therapy on this were investigated. Data of 108 patients
      (female/male (F/M) 27/81) were analyzed. Data on free T3, free T4, thyroid
      stimulating hormone, anti-thyroid peroxidase antibodies (TPO), anti-thyroglobulin
      antibodies, and thyroid ultrasound were assessed retrospectively. 44 (F/M 15/29)
      patients were receiving anti-TNF alpha, while 64 (F/M 12/52) were receiving other
      drugs [(sulfasalazine, anti-inflammatory drug (NSAIDs)]. Among those not
      receiving anti-TNF alpha therapy, TPO level was high in 23 patients (mean TPO
      value 86.69 +/- 65.28 U/ml), while it was high only in nine receiving anti-TNF
      alpha (mean TPO 36.61 +/- 14.02 U/ml) (p < 0.05). Investigating the data
      regarding gender in both populations, autoimmune thyroid disease frequency was
      found to be lower in the patient group receiving anti-TNF alpha treatment.
      Subclinical hyperthyroidism was discovered in three patients (one female two
      male), and subclinical hypothyroidism in two (two male). Thyroid nodule was
      detected in 29 patients. It was concluded that the frequency of thyroid
      autoimmune disease was higher in our study than that reported in the literature,
      and the frequency of thyroid disorder in patients with AS was lower in those
      receiving anti-TNF alpha compared to those not. This may arise from the role of
      TNF alpha on pathogenesis of thyroid disorders.

PMID- 22614218
TI  - TGF-beta autocrine pathway and MAPK signaling promote cell invasiveness and in
      vivo mammary adenocarcinoma tumor progression.
AB  - Breast cancer progression and metastasis have been linked to abnormal signaling
      by transforming growth factor-beta (TGF-beta) cytokines. In early-stage breast
      cancers, TGF-beta exhibits tumor suppressor activity by repressing cell
      proliferation and inducing cell death, whereas in advanced-stage tumors, TGF-beta
      promotes invasion and metastatic dissemination. The molecular mechanisms
      underlying pro-oncogenic activities of TGF-beta are not fully understood. The
      present study validates the role of TGF-beta signaling in cancer progression and
      explores mediators of pro-oncogenic TGF-beta activities using the LM3 mammary
      adenocarcinoma cell line, derived from a spontaneous murine mammary
      adenocarcinoma. Expression of kinase-inactive TGF-beta receptors decreased both
      basal and TGF-beta-induced invasion. Analysis of signal transduction mediators
      showed that p38MAPK and MEK contribute to TGF-beta stimulation of cell motility
      and invasion. TGF-beta disrupted the epithelial actin structures supporting cell
      cell adhesions, and increased linear actin filaments. Moreover, MEK and p38MAPK
      pathways showed opposite effects on actin remodeling in response to TGF-beta.
      Blockade of Raf-MEK signaling enhanced TGF-beta induction of actin stress-fibers
      whereas p38MAPK inhibitors blocked this effect. A novel observation was made that
      TGF-beta rapidly activates the actin nucleation Arp2/3 complex. In addition, TGF
      beta stimulated matrix metalloproteinase MMP-9 secretion via a MAPK-independent
      pathway. Experiments using syngeneic mice showed that kinase-inactive TGF-beta
      receptors inhibit the first stages of LM3 tumor growth in vivo. Our studies
      demonstrate that autocrine TGF-beta signaling contributes to the invasive
      behavior of mammary carcinoma cells. Moreover, we show that both MAPK-dependent
      and -independent pathways are necessary for TGF-beta-induced effects. Therefore,
      MEK-ERK and p38 MAPK pathways are potential venues for therapeutic intervention
      in pro-oncogenic TGF-beta signaling.

PMID- 22614220
TI  - Kinetics and mechanism of the heterogeneous reaction of N2O5 with mineral dust
      particles.
AB  - The heterogeneous interaction of N2O5 with Saharan dust particles was
      investigated using aerosol flow tubes with detection of N2O5 by cavity-ring-down
      spectroscopy. The uptake coefficient, gamma, was determined to be 0.02 +/- 0.01
      on airborne Saharan dust particles, independent of relative humidity (RH, 0-67%)
      and initial N2O5 concentration (5 * 10(11)-3 * 10(13) molecule cm(-3)). Analysis
      of gas- and particulate phase products suggests that N2O5 undergoes heterogeneous
      hydrolysis forming particulate nitrate. The independence of gamma on the initial
      N2O5 concentration indicates that, on the seconds time scale of these
      experiments, the heterogeneous reaction of N2O5 with dust particles is not
      restricted to the external particle surface but internal reactive sites are also
      available. The particles could be deactivated with respect to N2O5 uptake only
      when pre-treated with very high levels of HNO3. 

PMID- 22614221
TI  - The relaxant action of nicorandil in bovine tracheal smooth muscle.
AB  - The relaxant mechanisms of nicorandil were examined by comparing its effects with
      those of sodium nitroprusside and cromakalim in bovine tracheal smooth muscle. In
      preparations contracted with methacholine (0.3 MU mol/l) or high K(+)(40 mmol/l),
      nicorandil and sodium nitroprusside caused concentration-dependent relaxations.
      Their relaxant effects on high K(+) -contracted preparations were smaller than
      those on methacholine-contracted muscle. Cromakalim relaxed methacholine
      contracted preparations, whereas it had no effect on high K(+) -contracted
      muscle. The inhibitor of soluble guanylyl cyclase 1H-[1,2,4]oxadiazolo[4,3
      a]quinoxalin-1-one (ODQ; 5 mol/l) completely prevented the relaxation induced by
      lower concentrations ( <30 MU mol/l) of nicorandil,whereas it partially
      attenuated relaxation caused by higher concentrations. The ATP-sensitive K(+)
      (K(ATP)) channel blocker glibenclamide only partially attenuated the relaxant
      responses to nicorandil (at 100 and 300 MU mol/l). Combination treatment with ODQ
      and glibenclamide almost completely prevented nicorandil-induced relaxations. The
      large-conductance Ca2(+) -activated K(+) channel (Maxi K(+) channel) inhibitor
      iberiotoxin significantly prevented the relaxations induced by lower
      concentrations (3 and 10 MU mol/l) of nicorandil. The preventive effect of
      iberiotoxin was markedly enhanced under the blockade of K(ATP) channels with
      glibenclamide. These results suggest that nicorandil relaxes bovine tracheal
      smooth muscle through 2 mechanisms: opening of K(ATP) channels and activation of
      the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway. Nicorandil
      may also activate Maxi K(+) channels, possibly through the NO-cGMP pathway, and
      the interaction of K ATP channels and Maxi K(+) channels may affect the relaxant
      effect of nicorandilin bovine tracheal smooth muscle.

PMID- 22614222
TI  - Enhancement of neutral lipid productivity in the microalga Isochrysis affinis
      Galbana (T-Iso) by a mutation-selection procedure.
AB  - Microalgae offer a high potential for energetic lipid storage as well as high
      growth rates. They are therefore considered promising candidates for biofuel
      production, with the selection of high lipid-producing strains a major objective
      in projects on the development of this technology. We developed a mutation
      selection method aimed at increasing microalgae neutral lipid productivity. A two
      step method, based on UVc irradiation followed by flow cytometry selection, was
      applied to a set of strains that had an initial high lipid content and
      improvement was assessed by means of Nile-red fluorescence measurements. The
      method was first tested on Isochrysis affinis galbana (T-Iso). Following a first
      round of mutation-selection, the total fatty acid content had not increased
      significantly, being 262 +/- 21 mgTFA (gC)-1 for the wild type (WT) and 269 +/-
      49 mgTFA (gC)-1 for the selected population (S1M1). Conversely, fatty acid
      distribution among the lipid classes was affected by the process, resulting in a
      20% increase for the fatty acids in the neutral lipids and a 40% decrease in the
      phospholipids. After a second mutation-selection step (S2M2), the total fatty
      acid content reached 409 +/- 64 mgTFA (gC)-1 with a fatty acid distribution
      similar to the S1M1 population. Growth rate remained unaffected by the process,
      resulting in a 80% increase for neutral lipid productivity.

PMID- 22614223
TI  - Applications of real-time thermoregulatory models to occupational heat stress: 
      validation with military and civilian field studies.
AB  - A real-time thermoregulatory model using noninvasive measurements as inputs was
      developed for predicting physiological responses of individuals working long
      hours. The purpose of the model is to reduce heat-related injuries and illness by
      predicting the physiological effects of thermal stress on individuals while
      working. The model was originally validated mainly by using data from controlled
      laboratory studies. This study expands the validation of the model with field
      data from 26 test volunteers, including US Marines, Australian soldiers, and US
      wildland fire fighters (WLFF). These data encompass a range of environmental
      conditions (air temperature: 19-30 degrees  C; relative humidity: 25-63%) and
      clothing (i.e., battle dress uniform, chemical-biological protective garment,
      WLFF protective gear), while performing diverse activities (e.g., marksmanship,
      marching, extinguishing fires, and digging). The predicted core temperatures
      (Tc), calculated using environmental, anthropometric, clothing, and heart rate
      measures collected in the field as model inputs, were compared with subjects' Tc
      collected with ingested telemetry temperature pills. Root mean standard deviation
      (RMSD) values, used for goodness of fit comparisons, indicated that overall, the
      model predictions were in close agreement with the measured values (grand mean of
      RMSD: 0.15-0.38 degrees  C). Although the field data showed more individual
      variability in the physiological data relative to more controlled laboratory
      studies, this study showed that the performance of the model was adequate.

PMID- 22614224
TI  - Heat injury prevention--a military perspective.
AB  - Heat-related injuries, and specifically exertional heat stroke, are a significant
      occupational risk in the armed forces, especially for those soldiers who are
      rapidly deployed from a temperate climate region to hot climate regions.
      Traditionally, adaptation to heat was considered as a matter of physiological
      adaptation. It is clear today that these injuries are mostly avoidable when
      applying proper education and behavioral adaptations. Education on behavioral
      adaptation for the prevention of heat injuries should be targeted at the
      individual and the organization level. This article summarizes the issue of
      proper preventive measures that should be taken to avoid, or at least minimize,
      the risk of exertional heat related injuries during military operations and
      training.

PMID- 22614225
TI  - Marksmanship deficits caused by an exhaustive whole-body lifting task with and
      without torso-borne loads.
AB  - Studies of exhaustive exercise on marksmanship are inconclusive and have not
      measured trigger pull latencies (LAT) nor considered impact of added torso loads.
      This study examined the impact of exhaustive whole-body exercise and torso
      loading on accuracy, precision, and latency during a marksmanship test. Twelve
      men lifted a 20.5-kg box on to a 1.55-m high shelf until they could not maintain
      a 12 lifts.min-1 pace. Within 25 seconds of ending the lifting task, the subjects
      started a 10-minute rifle marksmanship test (8 shots.min-1). During lifting and
      shooting, the subjects wore 2 different loads: NOLOAD = boots, uniform, and
      helmet (5.9 kg) and LOAD = a torso-borne load (29.9 kg) + NOLOAD. With the LOAD,
      the subjects were only able to work for 69% as long, perform 31% as many lifts,
      or do 38% as much total work compared with the NOLOAD condition. Despite
      performing less total external work during LOAD, the heart rate (HR) was more
      than 25% higher than NOLOAD. Measures of accuracy and precision improved and
      stabilized after minute 3. Overall, LAT increased (p < 0.025) for LOAD (mean +/-
      SE, 2,522 +/- 81 milliseconds), compared with NOLOAD (2,240 +/- 121). During 0-4
      minutes, LAT for LOAD was 14% greater than for NOLOAD (p < 0.05); from 4 to 10
      minutes, LAT did not differ. Exhaustive whole-body exercise transiently degraded
      accuracy regardless of load. In the LOAD condition, LAT was immediately increased
      and sustained for 10 minutes; in the NOLOAD condition, LAT increased gradually.
      Although load did not decrease accuracy, it increased the time to engage targets,
      which can impact fighting effectiveness and survivability.

PMID- 22614227
TI  - Importance of sports during youth and exercise barriers in 20- to 29-year-old
      male nonathletes differently motivated for regular physical activities.
AB  - The number of sedentary young adults has dramatically increased in past decades,
      and sedentary lifestyles are adopted at an increasingly earlier age. Little is
      known about barriers or predictors to (re)initiate regular physical activity in
      this group. The purpose of the study is to (a) identify subgroups in nonathletes
      differing in their amenability to physical exercise, (b) to analyze them for
      differences in barriers and intention to exercise, and (c) compare importance of
      sports during youth in nonathletes to trained peers. Using a health and fitness
      questionnaire 589 nonathletes were queried in the cross-sectional survey and
      compared with 270 trained peers. Athletic abstainers (A), lower (L), and higher
      (H) motivated nonathletes were separated based on previous engagement in sports.
      Of the nonathletes, 54.7% reported only 1 barrier to exercise. Although this
      feature was most prominent in H (71.5%), the other groups showed significantly
      more barriers and a broader distribution. Similar characteristics but minor
      differences were observed for perceived importance of sports during youth. The
      most significant differences between athletes and nonathletes emerged enquiring
      the attitude and activity of the parents. The majority of nonathletes (72.8%)
      indicate their intention to exercise in the future. Their intention differed
      significantly in H (88.1%), L (76.1%), and A (59.1%). However, there are good
      reasons to doubt that most of those intending nonathletes will actually become
      physically active. Even in the analyzed narrow age range of men different
      motivated groups of nonathletes were found. Because of the differences in
      receptiveness and approachability health promotion policies may not only consider
      the often recommended tailored interventions but also carefully designed
      incentive programs.

PMID- 22614228
TI  - Effects of short-term quercetin supplementation on soldier performance.
AB  - The purpose was to assess the short-term effects of quercetin supplementation on
      aerobically demanding soldier performance. In a double-blind crossover study, 16
      male soldiers performed 3 days of aerobically demanding exercise under 3
      conditions: Baseline (B), Placebo (P), and Quercetin (Q). Day 1 was a treadmill
      V[Combining Dot Above]O2peak test. Days 2 and 3 were identical, consisting of 75
      minutes of loaded treadmill marching (LM) and a subsequent cycling time trial
      (TT) to complete 200 kJ of work. After B condition, the soldiers consumed 2
      energy bars, each containing 0 mg (placebo) or 500 mg of quercetin (1,000 mg.d-1)
      for 8.5 days. Beginning day 6 of supplementation, the soldiers performed the 3
      exercise days. There was a significant (p < 0.05) increase in plasma Q after Q
      supplementation. Repeated measures analyses of variance revealed no differences
      after P or Q supplementation as compared with B in V[Combining Dot Above]O2peak
      (B = 48.9 +/- 1.1, P = 49.3 +/- 1.1, Q = 48.8 +/- 1.2 ml.kg-1.min-1) or TT time
      (B = 18.4 +/- 1.0, P = 18.5 +/- 1.1, Q = 18.3 +/- 1.0 minutes [mean day 1 and day
      2]). The respiratory exchange ratio during LM did not differ across treatments (B
      = 0.87 +/- 0.03, P = 0.87 +/- 0.03, Q = 0.86 +/- 0.04 [mean day 1 and day 2]).
      Ratings of perceived exertion were not affected by Q supplementation during the
      V[Combining Dot Above]O2peak test, LM or TT. Supplementation of 1,000 mg.d-1 of
      quercetin for 8.5 days had no positive effect on aerobically demanding soldier
      performance. It is possible that a different dosing regimen, a combination of
      antioxidants or a different form of quercetin supplementation, may be needed to
      produce an increase in soldier performance.

PMID- 22614229
TI  - [Reccurent reflux ... and other problems following fundoplication: indication for
      re-operation].
AB  - BACKGROUND: Early function diagnostics and problem-oriented management are basic
      requirements in cases of functional problems and complications following
      antireflux surgery for gastroesophageal reflux disease (GERD). HISTORY,
      DIAGNOSTICS, AND THERAPEUTIC MANAGEMENT: A detailed history with a focus on the
      development of symptoms before and after the initial antireflux operation are
      fundamental prerequisites for a good diagnostic work-up. The data of preoperative
      function tests should always be reconsidered when re-evaluating a patient and be
      compared to the current findings. Thus, an analysis of the indications of any
      previous antireflux operation and an analysis of potential new or aggravated
      functional defects are essential. The general criteria indicating an operative
      procedure in gastroesophageal reflux disease do not change following such
      operation. Beyond these, symptomatic functional disorders caused by an antireflux
      operation may represent a new indication for an operative revision. INDICATION
      FOR RE-OPERATION: In the case of a symptomatic reflux recurrence, three essential
      criteria indicate an operative procedure: (i) a progressive type of GERD (proven
      functional defects, hiatal hernia, presence of typical reflux symptoms, necessity
      of increasing PPI dosage), (ii) non acid-dependent symptoms in spite of adequate
      medication (aspiration, volume reflux, pulmonary symptoms) and (iii) an
      alternative to medical therapy (preference, dependence, side effects, quality of
      life). In addition to these, symptomatic mechanical problems are important
      additional criteria for a redo procedure: the dissolution of the fundoplication
      wrap, the telescope-like slippage of the fundoplication around the proximal
      stomach ("slipped Nissen"), a paraesophageal herniation, and the transhiatal
      migration of an intact fundoplication. Finally, the rather seldom occurring wrong
      construction of the fundoplication and a not detected primary motility disorder
      (e. g., achalasia) are indications for redo surgery in most cases. CONCLUSION:
      The decision for any redo surgery following antireflux operations should always
      be based on a sound balance between symptomatic impairment and objective findings
      in functional disorders. This analysis allows for a responsible decision process
      since any redo surgery holds the risk of a lower success rate than the initial
      operation.

PMID- 22614230
TI  - [Creation of centres in high-volume hospitals -- promotor of communication].
AB  - The number of patients with a diagnosis of cancer is alarming: according to new
      figures from the Robert Koch Institute about 435 000 patients are diagnosed
      annually in Germany. 210 000 patients die annually of this diagnosis. Even if no
      significant progress in prevention has been achieved, in 2020 about 25 % more
      cases will be diagnosed. In the last two decades it has become established that
      an interdisciplinary treatment of tumour patients is necessary because the
      variety of different treatment options depending on an individual person cannot
      be mastered by one physician. The goal of the centres and certification is to
      establish a very concentrated expertise in large case numbers and quality-assured
      transparent treatment. The central requirement of a maximum-care centre is thus
      to enable communication under appropriate conditions. Promoting not only the
      space requirements, centre must also develop a treatment corridor and is
      responsible for further education. Additionally an oncology centre has a goal in
      communications, namely, to offer a treatment option for all patients in each
      stage of the disease, and to incorporate cancer patients in clinical trials.

PMID- 22614231
TI  - [Benchmarking surgical resources--a work sampling analysis at a German university
      hospital].
AB  - INTRODUCTION: Work densification caused by lack of young surgeons with increased
      clinical documentation keeps surgeons busy. It is proven by many studies that
      surgeons work significantly longer hours per week and deal with a larger amount
      of medical and non-medical documentation than staff members in conservative
      disciplines. The aim of the study was to investigate surgeons work distribution
      in a surgical university department and to evaluate by means of a work sampling
      analysis whether it can be standardised and slimmed down by systematic use of IT
      supported, process-managed work-flow. In addition the data obtained are compared
      wuith those from other studies on similar topics. METHODS: Based on the results
      of an independent pilot observational study, 21 surgeons (14 residents, 7 staff
      surgeons) had to document over a 10-day period in a self-observation once in an
      hour their actual activity in a two dimensional matrix concerning medical
      activity (13 items) and patient contact (5 items). After the study, each
      physician had to estimate his/her own work distribution. Real percentages of the
      self-observation study were compared to the physicians' estimates of work
      distribution. IT-supported clinical pathways have been implemented since 2004 in
      our department. RESULTS: Over a ten-day evaluation period (1830 observation
      points), surgeons spent 30.2% of their activity in the operating theatre or on
      direct patient care. During 13.9% they were in meetings and they spent 10.8% of
      their time on documentation. Time needed for studying medical records (9.2%) and
      ward rounds (9.0%) ranged in a similar way. There was a significant accordance of
      estimated and real work distribution concerning the 5 most frequent daily
      activities. In only 14% there was no direct patient relationship. CONCLUSION:
      Application of work sampling analysis in surgery is a valid procedure for the
      evaluation of work flows in the course of personal observations. Surgeons working
      time in a hospital is limited. To achieve a maximum of direct patient care,
      clinical documentation has to be optimised by process automatisation within the
      context of IT-supported clinical pathways. Surgeons are able to estimate very
      exactly the distribution of their daily activities so that data of working time
      estimations is valuable.

PMID- 22614232
TI  - [Vacuum therapy management of enteroatmospheric fistulae in the open abdomen].

PMID- 22614233
TI  - [Merkel cell carcinoma of the right cheek and spontaneous regression--case report
      and literature review].

PMID- 22614234
TI  - Ectoparasite reproductive performance when host condition varies.
AB  - Host condition can influence both the nutritive resources available to parasites
      and the strength of host defences. Since these factors are likely to be
      correlated, it is unclear whether parasites would be more successful on hosts in
      good, intermediate or poor conditions. For more complex parasites, like fleas,
      where larvae depend on adults to extract and make available some essential host
      resources, host condition can act at two levels. First, it can affect the
      investment of females into eggs, and second, it can influence offspring growth.
      In a two-step experiment, we first let female hen fleas Ceratophyllus gallinae
      feed on nestlings of reduced, control or enlarged great tit Parus major broods
      and secondly used the blood from these nestlings as a food source for flea larvae
      reared in the laboratory. We then assessed the effect of brood size manipulation
      on reproductive investment and survival of female fleas, and on survival,
      developmental time, mass and size of pre-imago larvae and adults of the first
      generation. Although host condition, measured as body mass controlled for body
      size, was significantly influenced by brood size manipulation, it did not affect
      the female fleas' reproductive investment and survival. Larvae fed with blood
      from nestlings of reduced broods lived longer, however, than larvae fed on blood
      from enlarged or control broods. Additionally, F1 adults grew shorter tibiae when
      their mother had fed on hosts of reduced broods. The finding that brood size
      manipulation influenced parasite reproduction suggests that it affected nutritive
      resources and/or host defence, but the precise mechanism or balance between the
      two requires further investigation.

PMID- 22614235
TI  - Reelin signalling in neuroblastoma: migratory switch in metastatic stages.
AB  - The essential functions of Reelin for the migratory behaviour of neuroblasts in
      the central nervous system are well documented. Its role in the dissemination of
      neuronal tumours of the peripheral nervous system has not been studied in detail.
      Here, we examined neuroblastoma (NB), a tumour derived from sympathoadrenal cells
      of neural crest origin. We studied the expression of Reelin, its receptors VLDLR
      and LRP8 and the adapter protein DAB1 in primary tumour samples and cell lines.
      We used real-time RT-PCR, immunohistology and western blot analysis. In NB cell
      lines we studied effects of all-trans retinoic acid and the in vitro effects of
      Reelin. In primary tumour samples of untreated patients, a significant
      downregulation of Reelin and DAB1 mRNA was found in the metastatic stages 3, 4
      and 4s. Immunohistochemical studies revealed expression of Reelin, LRP8 and DAB1
      in differentiating-type low-grade NB. In vitro, western blot analysis of selected
      NB cell lines showed variable expression patterns. Differentiation induction with
      all-trans retinoic acid induced the upregulation of Reelin and DAB1. Reelin acted
      as a chemoattractant for various NB cell lines but inhibited migration when
      applied together with the NB cells. In normal tissue, we found Reelin in
      lymphatic endothelial cells (LECs) but not in blood vessel endothelium (BECs). In
      primary NB, both BECs and LECs were positive. Our data strongly suggest that
      Reelin has a dual role in NB. Autocrine expression marks low-grade
      differentiating tumour cells, whereas paracrine Reelin presented by LECs and BECs
      may act as a chemoattractant and promote hematogenic and lymphogenic
      dissemination in progressed stages.

PMID- 22614238
TI  - NFKB1 polymorphism is associated with age-related gene methylation in
      Helicobacter pylori-infected subjects.
AB  - CpG island aberrant methylation is shown to be an important mechanism in gene
      silencing. The important role of NF-kappaB in the inflammatory response to H.
      pylori colonization has been indicated. We investigated the influence of NFKB1
      polymorphisms, -94 ins/del (rs28362491) and -449 C>G (rs72696119), on the
      aberrant gene methylation under H. pylori infection. Gastric mucosal samples were
      obtained from sub-subjects without malignancies. Methylation status of genes
      (p14ARF, p16INK4a, DAPK and CDH1) was determined by methylation-specific PCR
      (MSP). The genotyping of NFKB1 was performed by PCR-SSCP. There was a strong
      allelic association between rs28362491 and rs72696119, and all H. pylori-infected
      -94 del/del homozygotes had a -449 GG genotype. The -94 del/del homozygosity was
      significantly associated with risk for development of CpG island high methylation
      (CIHM) (two or more gene methylations), especially DAPK and CDH1 methylations,
      and the number of methylated genes was significantly higher in -94 del/del
      homozygotes than in ins/del and ins/ins (ins carrier) H. pylori-infected elder
      subjects. In addition, this methylated gene number was significantly increased
      with age in H. pylori-infected del/del homozygotes, but not in infected ins
      carriers. Furthermore, the inflammation score was significantly higher in H.
      pylori-infected del/del homozygotes compared to ins carriers. NFKB1 -94 ins/del
      ATTG polymorphism (rs28362491) was significantly associated with the increased
      risk for the development of age-related gene methylation in non-cancerous gastric
      mucosa under H. pylori-induced inflammation.

PMID- 22614236
TI  - Prevention of stroke in patients with atrial fibrillation: anticoagulant and
      antiplatelet options.
AB  - As the population ages, the prevalence of atrial fibrillation (AF) continues to
      rise. The most feared complication of this common cardiac arrhythmia is
      cardioembolic stroke. Strokes related to AF are associated with greater morbidity
      and mortality than ischemic strokes of most other etiologies and impose a
      substantial economic burden on healthcare systems around the world. Until
      recently, warfarin was the sole anticoagulant proven effective for stroke
      prevention patients with AF at elevated risk, but its narrow therapeutic margin
      and variable dose response limited clinical utility. The emergence of new
      anticoagulants that offer equal or superior efficacy, greater safety and the
      convenience of fixed oral dosing may make warfarin the less preferred option.
      This review provides an update on recent advancements in antithrombotic therapy
      for stroke prevention in patients with AF.

PMID- 22614237
TI  - Should rhythm control be preferred in younger atrial fibrillation patients?
AB  - PURPOSE: Rate- and rhythm control are two fundamental strategies to treat atrial
      fibrillation (AF). However, there are inconsistent results between clinical
      trials about which treatment should be preferred. The aims of this study were to
      systematically summarize the clinical trials and compare rate- and rhythm control
      strategies regarding composite outcome of all cause mortality, worsening heart
      failure, and thromboembolic and bleeding events. METHODS: English and non-English
      studies that were published from 1966 onwards were included in this meta-analysis
      if they were prospective randomized controlled trials which compared rate- and
      rhythm control strategies in patients with AF. The individual and combined
      outcomes were analyzed quantitatively with odds ratio and 95 % confidence
      interval. RESULTS: Ten prospective randomized controlled trials with 7,876
      patients were identified. There was no significant difference regarding primary
      composite outcome (11.47 vs. 11.03 % per year; odds ratio (OR), 1.03; 95 %
      confidence interval (CI), 0.90-1.20; P = 0.64) between rate- and rhythm control
      groups in overall age group. Meta-analysis for studies with mean age <65 years
      showed that rate control had significantly higher risk in primary composite
      outcome compared with rhythm control (8.74 vs. 4.80 % per year; OR, 1.89; 95 %CI,
      1.26-2.86; P = 0.002). CONCLUSIONS: A significant trend towards that rhythm
      control may be a preferable strategy for younger AF patients was observed in this
      study.

PMID- 22614239
TI  - Pre-dinner administration increases the efficacy of proton pump inhibitors on
      refractory GERD symptoms in connective tissue disease patients.
AB  - BACKGROUND: A significant proportion of patients with connective tissue disease
      (CTD) have gastric esophageal reflux disease (GERD) symptoms despite receiving
      proton pump inhibitors (PPIs). Although pre-meal administration of PPIs is
      recommended in Western countries, the benefit of this administration timing in
      Japanese CTD patients with refractory GERD symptoms has not been proven.
      OBJECTIVE: To determine whether pre-dinner administration of PPIs is more
      efficacious for refractory GERD symptoms in Japanese CTD patients. METHODS: CTD
      patients receiving oral PPIs were instructed to take PPIs 1 h before dinner.
      Gastrointestinal symptoms were evaluated with frequency scale for the symptoms of
      GERD (FSSG) and gastrointestinal symptom rating scale (GSRS) before and after the
      intervention. RESULTS: Pre-dinner administration of PPIs significantly improved
      FSSG total score, from a median of 8 to 6.5 (P = 0.005). Pre-dinner
      administration was more effective in patients with overt GERD symptoms (from
      median 18 to 10, P < 0.001) than in those with mild GERD symptoms (from median 2
      to 2, P = 0.201). In addition to reflux syndrome, pre-dinner administration of
      PPIs significantly decreased abdominal pain syndrome and constipation syndrome of
      GSRS. CONCLUSION: Pre-dinner administration of PPIs may increase their efficacy
      in Japanese CTD patients with GERD, especially those with overt symptoms.

PMID- 22614240
TI  - A click chemistry route to 2-functionalised PEGylated and cationic beta
      cyclodextrins: co-formulation opportunities for siRNA delivery.
AB  - A new approach to the synthesis of amphiphilic beta-cyclodextrins has used
      'click' chemistry to selectively modify the secondary 2-hydroxyl group. The
      resulting extended polar groups can be either polycationic or neutral PEGylated
      groups and these two amphiphile classes are compatible in dual cyclodextrin
      formulations for delivery of siRNA. When used alone with an siRNA, a cationic
      cyclodextrin was shown to have good transfection properties in cell culture. Co
      formulation with a PEGylated cyclodextrin altered the physicochemical properties
      of nanoparticles formed with siRNA. Improved particle properties included lower
      surface charges and reduced tendency to aggregate. However, as expected, the
      transfection efficiency of the cationic vector was lowered by co-formulation with
      the PEGylated cyclodextrin, requiring future surface modification of particles
      with targeting ligands for effective siRNA delivery.

PMID- 22614241
TI  - International evidence-based recommendations on ultrasound-guided vascular
      access.
AB  - PURPOSE: To provide clinicians with an evidence-based overview of all topics
      related to ultrasound vascular access. METHODS: An international evidence-based
      consensus provided definitions and recommendations. Medical literature on
      ultrasound vascular access was reviewed from January 1985 to October 2010. The
      GRADE and the GRADE-RAND methods were utilised to develop recommendations.
      RESULTS: The recommendations following the conference suggest the advantage of 2D
      vascular screening prior to cannulation and that real-time ultrasound needle
      guidance with an in-plane/long-axis technique optimises the probability of needle
      placement. Ultrasound guidance can be used not only for central venous
      cannulation but also in peripheral and arterial cannulation. Ultrasound can be
      used in order to check for immediate and life-threatening complications as well
      as the catheter's tip position. Educational courses and training are required to
      achieve competence and minimal skills when cannulation is performed with
      ultrasound guidance. A recommendation to create an ultrasound curriculum on
      vascular access is proposed. This technique allows the reduction of infectious
      and mechanical complications. CONCLUSIONS: These definitions and recommendations
      based on a critical evidence review and expert consensus are proposed to assist
      clinicians in ultrasound-guided vascular access and as a reference for future
      clinical research.

PMID- 22614242
TI  - Predicting caries by measuring its activity using quantitative light-induced
      fluorescence in vivo: a 2-year caries increment analysis.
AB  - The aim of this study was to analyse the predictive power of several clinical
      baseline parameters and the de-/remineralisation properties of in vivo etched
      sites measured with quantitative light-induced fluorescence (QLF) for subsequent
      2-year caries increment. At baseline, in 44 children (8.23 +/- 1.5 years) two
      areas (diameter 2 mm) of the buccal surface of a primary posterior tooth were
      etched with 36% phosphoric acid gel for 1 and 4 min, respectively. The etched
      sites were analysed immediately after etching (DeltaQ1) and 24 h (DeltaQ2) later
      by QLF. Additionally, caries status (deft/DMFT and initial caries), approximal
      plaque, bleeding on probing, and the patient's current use of fluorides were
      recorded. In the 2-year follow-up, 29 children were re-assessed. After clinical
      examination, the caries increment was calculated (DeltaDMFT) and correlated with
      the baseline clinical variables and the QLF readings. Results showed a
      significant positive correlation between DeltaQ(1 min) and the DeltaDMFT (r =
      0.44, p = 0.02). The DeltaDMFT was significantly correlated with the baseline
      deft (r = 0.56, p = 0.002), cavitated active caries lesions (r = 0.52, p =
      0.003), and filled teeth (r = 0.53, p = 0.003). In a regression analysis the use
      of fluoridated salt (SC = -0.10) and fluoride gel (SC = -0.14) were negatively
      associated with DeltaDMFT. In conclusion, these findings suggest that the
      demineralisation properties of the etched sites and the outcome of the 24-hour
      measurements with QLF are significantly associated with caries increment.
      Previous caries experience strongly correlated with caries increment in this
      group of children.

PMID- 22614243
TI  - Cytotoxic activity of the novel Akt inhibitor, MK-2206, in T-cell acute
      lymphoblastic leukemia.
AB  - T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive neoplastic disorder
      arising from T-cell progenitors. T-ALL accounts for 15% of newly diagnosed ALL
      cases in children and 25% in adults. Although the prognosis of T-ALL has
      improved, due to the use of polychemotherapy schemes, the outcome of
      relapsed/chemoresistant T-ALL cases is still poor. A signaling pathway that is
      frequently upregulated in T-ALL, is the phosphatidylinositol 3-kinase/Akt/mTOR
      network. To explore whether Akt could represent a target for therapeutic
      intervention in T-ALL, we evaluated the effects of the novel allosteric Akt
      inhibitor, MK-2206, on a panel of human T-ALL cell lines and primary cells from T
      ALL patients. MK-2206 decreased T-ALL cell line viability by blocking leukemic
      cells in the G(0)/G(1) phase of the cell cycle and inducing apoptosis. MK-2206
      also induced autophagy, as demonstrated by an increase in the 14-kDa form of
      LC3A/B. Western blotting analysis documented a concentration-dependent
      dephosphorylation of Akt and its downstream targets, GSK-3alpha/beta and FOXO3A,
      in response to MK-2206. MK-2206 was cytotoxic to primary T-ALL cells and induced
      apoptosis in a T-ALL patient cell subset (CD34(+)/CD4(-)/CD7(-)), which is
      enriched in leukemia-initiating cells. Taken together, our findings indicate that
      Akt inhibition may represent a potential therapeutic strategy in T-ALL.

PMID- 22614245
TI  - Misidentification of Brucella melitensis as Bergeyella zoohelcum by MicroScan
      WalkAway(r): a case report.
AB  - OBJECTIVE: To describe the misidentification of Brucella melitensis as Bergeyella
      zoohelcum by MicroScan WalkAway(r), a commonly used bacterial identification
      system. CLINICAL PRESENTATION AND INTERVENTION: A 35-year-old man was admitted to
      the Intensive Care Unit with sepsis syndrome. Three sets of aerobic blood culture
      samples were positive after 48 h of incubation. The isolated organism was
      identified as B. zoohelcum using the MicroScan WalkAway (Siemens Healthcare
      Diagnostics Inc., West Sacramento, Calif., USA). However, due to the rareness of
      the pathogen, the isolate was reidentified as B. melitensis with Vitek(r) 2
      system and later 16S ribosomal sequence analysis confirmed the isolate as B.
      melitensis having 100% match. CONCLUSION: This case showed that Brucella can be
      misidentified using MicroScan WalkAway. Countries where brucellosis is endemic
      need to be careful while using such automated identification systems in order not
      to miss the diagnosis of Brucella.

PMID- 22614246
TI  - Considering the role of semantic memory in episodic future thinking: evidence
      from semantic dementia.
AB  - Semantic dementia is a progressive neurodegenerative condition characterized by
      the profound and amodal loss of semantic memory in the context of relatively
      preserved episodic memory. In contrast, patients with Alzheimer's disease
      typically display impairments in episodic memory, but with semantic deficits of a
      much lesser magnitude than in semantic dementia. Our understanding of episodic
      memory retrieval in these cohorts has greatly increased over the last decade,
      however, we know relatively little regarding the ability of these patients to
      imagine and describe possible future events, and whether episodic future thinking
      is mediated by divergent neural substrates contingent on dementia subtype. Here,
      we explored episodic future thinking in patients with semantic dementia (n=11)
      and Alzheimer's disease (n=11), in comparison with healthy control participants
      (n=10). Participants completed a battery of tests designed to probe episodic and
      semantic thinking across past and future conditions, as well as standardized
      tests of episodic and semantic memory. Further, all participants underwent
      magnetic resonance imaging. Despite their relatively intact episodic retrieval
      for recent past events, the semantic dementia cohort showed significant
      impairments for episodic future thinking. In contrast, the group with Alzheimer's
      disease showed parallel deficits across past and future episodic conditions.
      Voxel-based morphometry analyses confirmed that atrophy in the left inferior
      temporal gyrus and bilateral temporal poles, regions strongly implicated in
      semantic memory, correlated significantly with deficits in episodic future
      thinking in semantic dementia. Conversely, episodic future thinking performance
      in Alzheimer's disease correlated with atrophy in regions associated with
      episodic memory, namely the posterior cingulate, parahippocampal gyrus and
      frontal pole. These distinct neuroanatomical substrates contingent on dementia
      group were further qualified by correlational analyses that confirmed the
      relation between semantic memory deficits and episodic future thinking in
      semantic dementia, in contrast with the role of episodic memory deficits and
      episodic future thinking in Alzheimer's disease. Our findings demonstrate that
      semantic knowledge is critical for the construction of novel future events,
      providing the necessary scaffolding into which episodic details can be
      integrated. Further research is necessary to elucidate the precise contribution
      of semantic memory to future thinking, and to explore how deficits in self
      projection manifest on behavioural and social levels in different dementia
      subtypes.

PMID- 22614244
TI  - Coordinated dysregulation of mRNAs and microRNAs in the rat medial prefrontal
      cortex following a history of alcohol dependence.
AB  - Long-term changes in brain gene expression have been identified in alcohol
      dependence, but underlying mechanisms remain unknown. Here, we examined the
      potential role of microRNAs (miRNAs) for persistent gene expression changes in
      the rat medial prefrontal cortex (mPFC) after a history of alcohol dependence.
      Two-bottle free-choice alcohol consumption increased following 7-week exposure to
      intermittent alcohol intoxication. A bioinformatic approach using microarray
      analysis, quantitative PCR (qPCR), bioinformatic analysis and microRNA-messenger
      RNA (mRNA) integrative analysis identified expression patterns indicative of a
      disruption in synaptic processes and neuroplasticity. About 41 rat miRNAs and 165
      mRNAs in the mPFC were significantly altered after chronic alcohol exposure. A
      subset of the miRNAs and mRNAs was confirmed by qPCR. Gene ontology categories of
      differential expression pointed to functional processes commonly associated with
      neurotransmission, neuroadaptation and synaptic plasticity. microRNA-mRNA
      expression pairing identified 33 miRNAs putatively targeting 89 mRNAs suggesting
      transcriptional networks involved in axonal guidance and neurotransmitter
      signaling. Our results demonstrate a significant shift in microRNA expression
      patterns in the mPFC following a history of dependence. Owing to their global
      regulation of multiple downstream target transcripts, miRNAs may have a pivotal
      role in the reorganization of synaptic connections and long-term neuroadaptations
      in alcohol dependence. MicroRNA-mediated alterations of transcriptional networks
      may be involved in disrupted prefrontal control over alcohol drinking observed in
      alcoholic patients.

PMID- 22614247
TI  - Induced changes in protein receptors conferring resistance to anesthetics.
AB  - PURPOSE OF REVIEW: Although general anesthetics have been provided effectively
      for many years, their exact molecular underpinnings remain relatively unknown. In
      this article, we discuss the recent findings associated with resistance to
      anesthetic effects as a way of shedding light on these mechanisms. RECENT
      FINDINGS: The original theories of anesthetic action based upon their effects on
      cellular membranes have given way to specific theories concerning direct effects
      on ion channel proteins. These molecular targets are intimately involved in the
      conduct of neuronal signaling within the central nervous system and are thought
      to be essential in the modulation of conscious states. It is the lack of a
      thorough understanding of unperturbed consciousness that fosters great difficulty
      in understanding how anesthetics alter this conscious state. However, one very
      fruitful line of analysis in the quest for such answers lies in the examination
      of both in-vitro and in-vivo ion channel systems that seem to maintain variable
      levels of resistance to anesthetics. SUMMARY: Information about the possible
      targets and molecular nature of anesthetic action is being derived from studies
      of anesthetic resistance in gamma aminobutyric acid receptors, tandem pore
      potassium channels, and an apparently wide variety of protein systems within the
      nematode, Caenorhabditis elegans.

PMID- 22614248
TI  - Anesthetic management of endovascular procedures for cerebrovascular
      atherosclerosis.
AB  - PURPOSE OF REVIEW: The article reviews the treatment options for cerebrovascular
      atherosclerosis and highlights the challenges of anesthesia in this complex group
      of patients. RECENT FINDINGS: Percutaneous transluminal angioplasty and stenting
      is a treatment option for cerebrovascular atherosclerosis in patients at high
      risk of stroke despite maximal medical therapy and control of risk factors. The
      majority of carotid lesions are treated using regional anesthesia, but general
      anesthesia is currently the technique of choice for intracranial lesions because
      of the length of the procedures and the need for immobility. There is no evidence
      to guide optimal anesthetic management in this group of patients in whom
      significant comorbidities are common. The risks of myocardial ischemia,
      cardiovascular instability and cerebral ischemia and hyperperfusion are high, and
      anesthesia management should be directed towards their prevention, recognition
      and treatment. SUMMARY: The anesthetist plays a key role in the endovascular
      management of patients with cerebrovascular atherosclerosis. Optimization of
      comorbidities, meticulous control of systemic physiologic variables and
      aggressive management of complications contribute to enhanced patient outcome.

PMID- 22614249
TI  - Monod-Wyman-Changeux allosteric mechanisms of action and the pharmacology of
      etomidate.
AB  - PURPOSE OF REVIEW: Formal Monod-Wyman-Changeux allosteric mechanisms have proven
      valuable in framing research on the mechanism of etomidate action on its major
      molecular targets, gamma-aminobutyric acid type A (GABAA) receptors. However, the
      mathematical formalism of these mechanisms makes them difficult to comprehend.
      RECENT FINDINGS: We illustrate how allosteric models represent shifting
      equilibria between various functional receptor states (closed versus open) and
      how co-agonism can be readily understood as simply addition of gating energy
      associated with occupation of distinct agonist sites. We use these models to
      illustrate how the functional effects of a point mutation, alpha1M236W, in GABAA
      receptors can be translated into an allosteric model phenotype. SUMMARY:
      Allosteric co-agonism provides a robust framework for design and interpretation
      of structure-function experiments aimed at understanding where and how etomidate
      affects its GABAA receptor target molecules.

PMID- 22614250
TI  - Contribution of IL12A and IL12B polymorphisms to the risk of cervical cancer.
AB  - We studied the contribution of the IL12A 3'UTR G>A (rs568408) and IL12B 3'UTR A>C
      (rs3212227) polymorphisms to the risk of cervical cancer. These polymorphisms
      were genotyped in four hundred-five patients with cervical cancer and four
      hundred fifty unrelated healthy females from the Polish population. Logistic
      regression analysis adjusting for age, pregnancy, oral contraceptive use, tobacco
      smoking, and menopausal status revealed that the IL12B 3'UTR A>C polymorphism
      could be a genetic risk factor for cervical cancer. The adjusted odds ratio (OR)
      for patients with the A/C genotype vs A/A genotype was 1.557 (95 % CI = 1.173
      2.066, p = 0.0178) and adjusted OR for the C/C or A/C genotype vs the A/A
      genotype was 1.635 (95 % CI = 1.241-2.153, p = 0.0125). However, logistic
      regression analysis did not show an association of the IL12A 3'UTR G>A
      polymorphism with cervical cancer development in the studied Polish population.
      Our studies confirmed that the IL12B 3'UTR A>C polymorphism may be a genetic risk
      factor for cervical cancer.

PMID- 22614251
TI  - Phase II study of neoadjuvant chemotherapy with irinotecan hydrochloride and
      nedaplatin followed by radical hysterectomy for bulky stage Ib2 to IIb, cervical
      squamous cell carcinoma: Japanese Gynecologic Oncology Group study (JGOG 1065).
AB  - The efficacy and adverse events of neoadjuvant chemotherapy with irinotecan
      hydrochloride and nedaplatin were evaluated in patients with bulky stage Ib2 to
      IIb cervical squamous cell carcinoma. Eligibility included patients who received
      irinotecan (60 mg/m2) on days 1 and 8 and nedaplatin (80 mg/m2) on day 1 of a 21
      day cycle. After 1-3 courses of chemotherapy, radical hysterectomy was performed.
      Sixty-eight patients were enrolled. Sixty-six were included in the full analysis
      set. Their median age was 47 years (range 22-71), the FIGO stage was Ib2 in 18
      patients, IIa in 10, and IIb in 38. Radical hysterectomy was performed after NAC
      in 63 patients (95.5%). The number of administered courses of NAC was 1 in 13
      patients, 2 in 43, and 3 in 10. The response rate, the primary endpoint of this
      study, was 75.8% (CR in 2 patients, PR in 48, SD in 12, PD in 0, and NE in 4).
      The mean number of treatment courses required for a response was 1.42 (1 course
      in 30 patients, 2 courses in 19, and 3 courses in 1). The incidences of grade 3
      or 4 hematological toxicities were: neutropenia 72.2%, leukopenia 16.7%, anemia
      13.6%, thrombocytopenia 7.6%, febrile neutropenia 1.5%, and elevations of alanine
      aminotransferase and aspartate aminotransferase 1.5%. Grade 3 or 4 non
      hematologic toxicities were as follows: diarrhea 6.1%, nausea 3%, anorexia 1.5%,
      vomiting 1.5%, fever 1.5%, allergic reactions 1.5%, ileus 1.5% and vesicovaginal
      fistula 1.5%. Neoadjuvant chemotherapy with irinotecan and nedaplatin was an
      effective and well-tolerated treatment for patients with bulky stage Ib2 to IIb
      squamous cell carcinoma of the uterine cervix.

PMID- 22614252
TI  - Differences in proliferation, differentiation, and cytokine production by bone
      cells seeded on titanium-nitride and cobalt-chromium-molybdenum surfaces.
AB  - Titanium-nitride coating is used to improve cobalt-chromium-molybdenum implant
      survival in total knee arthroplasty, but its effect on osteoconduction is
      unknown. Chromium and cobalt ions negatively affect the growth and metabolism of
      cultured osteoblasts while enhancing osteoclastogenic cytokine production.
      Therefore, it was hypothesized that a titanium-nitride surface would enhance
      osteoblast proliferation and/or differentiation and reduce osteoclastogenic
      cytokine production compared with a cobalt-chromium-molybdenum surface. MC3T3-E1
      osteoblasts showed increased proliferation and decreased differentiation on
      titanium-nitride, while cytokine interleukin-6 production was higher on porous
      cobalt-chromium-molybdenum (p < 0.05), though interleukin-1beta was occasionally
      detected on both surfaces. These findings suggest improved osteoconduction on
      titanium-nitride compared with cobalt-chromium-molybdenum surface. 

PMID- 22614253
TI  - Tube pharyngostomy--a useful alternative for long-term enteric decompression or
      enteral feeding.
AB  - The tube pharyngostomy has been all but forgotten in recent years, and rightfully
      so when a PEG or PEJ is possible. Nevertheless, the tube pharyngostomy should
      remain in the armamentarium of the GI surgeon for selected patients in whom
      longer term enteral access is not available by PEG or PEJ for various technical
      reasons, for those who absolutely refuse a nasoenteric tube, or as terminal
      palliation in patients with nonoperable but obstructing intra-abdominal
      neoplasms. Not only is it easy to place (albeit requiring a brief general
      anesthetic), but these tubes are much more comfortable than the "misery" to the
      patient of a nasoenteric tube by avoiding the annoying nasal and nasopharyngeal
      irritation,sinusitis, trouble with speech and coughing, and general discomfort of
      a longer term, indwelling nasoenteric tube. Moreover, the tube can be hidden
      under a turtleneck-types weater, thereby avoiding the social discomfort of a tube
      exiting the nares. The overall lack of experience and ignorance, not only with
      these tubes but also with their concept, has precluded many surgeons from
      recognizing their usefulness,albeit in highly selected patients. With these
      advantages and caveats in mind, the tube pharyngostomy can prove a valuable
      adjunct in selected patients.

PMID- 22614254
TI  - The Paterno-Buchi reaction: importance of triplet states in the excited-state
      reaction pathway.
AB  - The Paterno-Buchi (PB) reaction between an excited carbonyl compound and an
      alkene has been widely studied, but so far little is known about the excited
      state dynamics of the reaction. In this investigation, we used a compound in
      which a formyl and a vinyl group are attached to a [2.2]paracyclophane in order
      to obtain a model system in pre-reactive conformation for the PB reaction. We
      studied the excited-state dynamics of the isolated molecule in a molecular beam
      using femtosecond time-resolved photoelectron spectroscopy and ab initio
      calculations. The results show that inter-system crossing within two picoseconds
      competes efficiently with the reaction in the singlet manifold. Thus, the PB
      reaction in this model system takes place in the triplet state on a time scale of
      nanoseconds. This result stresses the importance of triplet states in the excited
      state pathway of the PB reaction involving aromatic carbonyl compounds, even in
      situations in which the reacting moieties are in immediate vicinity. 

PMID- 22614255
TI  - Expression of phytochelatin synthase from aquatic macrophyte Ceratophyllum
      demersum L. enhances cadmium and arsenic accumulation in tobacco.
AB  - Phytochelatin synthase (PCS), the key enzyme involved in heavy metal
      detoxification and accumulation has been used from various sources to develop
      transgenic plants for the purpose of phytoremediation. However, some of the
      earlier studies provided contradictory results. Most of the PCS genes were
      isolated from plants that are not potential metal accumulators. In this study, we
      have isolated PCS gene from Ceratophyllum demersum cv. L. (CdPCS1), a submerged
      rootless aquatic macrophyte, which is considered as potential accumulator of
      heavy metals. The CdPCS1 cDNA of 1,757 bp encodes a polypeptide of 501 amino acid
      residues and differs from other known PCS with respect to the presence of a
      number of cysteine residues known for their interaction with heavy metals.
      Complementation of cad1-3 mutant of Arabidopsis deficient in PC (phytochelatin)
      biosynthesis by CdPCS1 suggests its role in the synthesis of PCs. Transgenic
      tobacco plants expressing CdPCS1 showed several-fold increased PC content and
      precursor non-protein thiols with enhanced accumulation of cadmium (Cd) and
      arsenic (As) without significant decrease in plant growth. We conclude that
      CdPCS1 encodes functional PCS and may be part of metal detoxification mechanism
      of the heavy metal accumulating plant C. demersum. KEY MESSAGE: Heterologous
      expression of PCS gene from C. demersum complements Arabidopsis cad1-3 mutant and
      leads to enhanced accumulation of Cd and As in transgenic tobacco.

PMID- 22614256
TI  - Extensive citrus triploid hybrid production by 2x*4x sexual hybridizations and
      parent-effect on the length of the juvenile phase.
AB  - The citrus fresh market demands the production of seedless citrus fruits, as
      seedy fruits are not accepted by consumers. The recovery of triploid plants has
      proven to be the most promising approach to achieve this goal, since triploids
      have very low fertility, are generally seedless and do not induce seeds in other
      cultivars by cross pollination. Triploid plants can be recovered by 2x*4x sexual
      hybridization. In this work, we present an effective methodology to recover
      triploid plants from 2x*4x hybridizations based on in vitro embryo rescue, ploidy
      level analysis by flow cytometry and genetic origin of triploid plants. The
      pollen viability of diploid and tetraploid citrus genotypes was analyzed by
      comparing the pollen germination rate in vitro. The pollen viability of
      tetraploid (doubled-diploid) genotypes is generally reduced but sufficient for
      successful pollination. Triploid embryos were identified in normal and
      undeveloped seeds that did not germinate under greenhouse conditions. The
      influence of parents and environmental conditions on obtaining triploid plants
      was analyzed and a strong interaction was noted between the parents and
      environmental conditions. The parental effect on the length of the juvenile phase
      was also demonstrated through observations of a large number of progeny over the
      last 15 years. The juvenile phase length of the triploid hybrids obtained with
      'Fortune' mandarin as female parent and tetraploid 'Orlando' tangelo as male
      parent was shorter than the juvenile phase obtained with a clementine as female
      parent and tetraploids of 'Nova', 'W. Leaf' and 'Pineapple' male parents. KEY
      MESSAGE: Effective methodology to recover citrus triploid plants from 2x*4x
      sexual hybridizations and the parental effect on the length of the juvenile
      phase.

PMID- 22614257
TI  - Study of the influence of the penetration enhancer isopropyl myristate on the
      nanostructure of stratum corneum lipid model membranes using neutron diffraction
      and deuterium labelling.
AB  - In order to elucidate the mode of action of the lipophilic penetration enhancer
      isopropyl myristate (IPM) on a molecular scale, we investigated oriented
      quaternary stratum corneum (SC) lipid model membranes based on ceramide AP,
      cholesterol, palmitic acid and cholesterol sulfate containing 10 wt% IPM by means
      of neutron diffraction. Our results indicate that IPM affects the lamellar lipid
      assembly in terms of bilayer perturbation and disordering. Phase segregation
      occurred, indicating that IPM is not likely to mix properly with the other SC
      lipids due to its branched structure. We used selective deuterium labelling to
      localize the penetration enhancer, and could successfully prove the presence of
      IPM in the two coexisting lamellar phases. We conclude that IPM's mode of action
      as penetration promoter is presumably based on incorporation into the SC lipid
      matrix, extraction of certain SC lipids into a separate phase and perturbation of
      the multilamellar lipid assembly.

PMID- 22614258
TI  - Casein kinase 2 inhibition modulates the DNA damage response but fails to
      radiosensitize malignant glioma cells.
AB  - Inhibitors of casein kinase 2 (CK2), a regulator of cell proliferation and
      mediator of the DNA damage response, are being evaluated in clinical trials for
      the treatment of cancers. Apigenin was capable of inhibiting the activation of
      CK2 following gamma irradiation in LN18 and U87 malignant glioma cells. Apigenin
      and siRNA-mediated CK2 protein depletion further inhibited NF-kappaB activation
      and altered the Tyr68 phosphorylation of Chk2 kinase, a DNA damage response
      checkpoint kinase, following irradiation. However, CK2 inhibition did not
      decrease the ability of these glioma cells to repair double-strand DNA breaks, as
      assessed by COMET assays and gamma-H2Ax staining. Likewise, apigenin and siRNA
      induced depletion of CK2 failed to sensitize glioma cells to the cytotoxic effect
      of 2 to 10 G-rays of gamma irradiation, as assessed by clonogenic assays. These
      results contrast with those found in other cancer types, and urge to prudence
      regarding the inclusion of malignant glioma patients in clinical trials that
      assess the radiosensitizing role of CK2 inhibitors in solid cancers.

PMID- 22614259
TI  - Impact of single-dose application of TGF-beta, copper peptide, stanozolol and
      ascorbic acid in hydrogel on midline laparatomy wound healing in a diabetic mouse
      model.
AB  - Despite numerous advances and improvements in surgical techniques the incidence
      of incisional hernias after laparotomy remains high. The aim of this study was to
      investigate possible effects of single application of ascorbic acid, stanozolol,
      a synthetic anabolic steroid, copper peptide and transforming growth factor-beta
      (TGF-beta) on laparotomy wound healing in an incisional wound model in diabetic
      mice. After diabetes induction with streptozotozin in Balb-c mice, midline
      laparatomies were carried out. Closure of the linea alba was followed by single
      dose application of the agents dissolved in a hydrogel before skin closure. The
      functional outcome was assessed in terms of maximum tensile strength. In
      addition, vessel densities, collagen contents and proliferation, were measured.
      The breaking strength of the skin 14 days after surgery was significantly higher
      in ascorbic acid (AlphaAlpha)-treated incisional wounds, whereas the other agents
      did not show a significantly better functional outcome. No significant
      differences were seen in vessel densities. Collagen type III contents was higher
      in the AlphaAlpha-treated animals, whereas the percentage of Ki67-positive nuclei
      was lower compared to the other groups. These data underline the positive effect
      of topically applied ascorbic acid in wound healing.

PMID- 22614260
TI  - Attention to pain and fear of pain in patients with chronic pain.
AB  - To investigate how acceptance of illness affects chronic pain in terms of
      attention towards pain and fearful thinking of pain. 62 participants (50 women)
      with chronic pain carried a palmtop computer for 2 weeks. Eight times each day
      auditory signals were delivered to cue participants to complete questions about
      their experience. Multilevel analyses indicated that on moments with more intense
      pain, more fearful thinking about pain, and less positive emotions, attention to
      pain was increased. Illness acceptance did not moderate the relation between pain
      intensity and attention to pain. Results further indicated that on moments with
      more intense pain, more negative emotions, and less positive emotions, fearful
      thinking about pain was increased. Of particular interest was the finding that
      the relationship between pain intensity and fearful thinking about pain was less
      strong for those high in acceptance. Pain captures attention and elicits fearful
      thinking about pain. Acceptance may be a useful avenue to lower negative thinking
      about pain, and to increase well-being in patients with chronic illnesses.

PMID- 22614261
TI  - Geographic variation in salt marsh structure and function.
AB  - We examined geographic variation in the structure and function of salt marsh
      communities along the Atlantic and Gulf coasts of the United States. Focusing on
      the arthropod community in the dominant salt marsh plant Spartina alterniflora,
      we tested two hypotheses: first, that marsh community structure varies
      geographically, and second, that two aspects of marsh function (response to
      eutrophication and addition of dead plant material) also vary geographically. We
      worked at eleven sites on the Gulf Coast and eleven sites on the Atlantic Coast,
      dividing each coast up into two geographic areas. Abiotic conditions (tidal
      range, soil organic content, and water content, but not soil salinity), plant
      variables (Spartina nitrogen content, height, cover of dead plant material, but
      not live Spartina percent cover or light interception), and arthropod variables
      (proportional abundances of predators, sucking herbivores, stem-boring
      herbivores, parasitoids, and detritivores, but not total arthropod numbers)
      varied among the four geographic regions. Latitude and mean tidal range explained
      much of this geographic variation. Nutrient enrichment increased all arthropod
      functional groups in the community, consistent with previous experimental
      results, and had similar effects in all geographic regions, contrary to our
      hypothesis, suggesting widespread consistency in this aspect of ecosystem
      function. The addition of dead plant material had surprisingly little effect on
      the arthropod community. Our results caution against the uncritical extrapolation
      of work done in one geographic region to another, but indicate that some aspects
      of marsh function may operate in similar ways in different geographic regions,
      despite spatial variation in community structure.

PMID- 22614262
TI  - Do the antiherbivore traits of expanding leaves in the Neotropical tree Inga
      paraensis (Fabaceae) vary with light availability?
AB  - Treefall gaps in tropical forests have a profound effect on plants growing in the
      understory, primarily due to increased light availability. In higher light,
      mature leaves typically have increased anti-herbivore defenses. However, since
      the majority of herbivory occurs while leaves are expanding, it is important to
      determine whether defense expression during the short period of leaf expansion is
      canalized (invariant) or plastic in response to variation in light. Therefore, we
      examined young leaves of Inga paraensis (Fabaceae) saplings growing along a light
      gradient in a terra-firme forest in Central Amazonia. We quantified leaf
      production and expansion time, dry mass of phenolics, saponins, and nitrogen,
      ants attracted to extrafloral nectaries, and leaf consumption. Over the entire
      light gradient, the number of leaves produced per flush increased by 50 % and the
      mass of phenolic compounds by 20 %, but no other traits changed. On average, 39 %
      of leaf area was consumed with no difference across the light gradient. Alone,
      none of the leaf traits was a significant predictor of leaf consumption, except
      for phenolics, which showed a positive relationship. Multiple regressions showed
      that leaf consumption was positively related to more leaves per flush and a
      higher concentration of phenolics in leaves. Unlike studies of mature leaves,
      young leaves of I. paraensis show low plasticity in defense traits across a light
      gradient, suggesting that leaf development is canalized.

PMID- 22614263
TI  - Consequences of exclusion of precipitation on microorganisms and microbial
      consumers in montane tropical rainforests.
AB  - The structure and functioning of decomposer systems heavily relies on soil
      moisture. However, this has been primarily studied in temperate ecosystems;
      little is known about how soil moisture affects the microfaunal food web in
      tropical regions. This lack of knowledge is surprising, since the microfaunal
      food web controls major ecosystem processes. To evaluate the role of
      precipitation in the structure of soil food web components (i.e., microorganisms
      and testate amoebae), we excluded water input by rain in montane rainforests at
      different altitudes in Ecuador. Rain exclusion strongly reduced microbial biomass
      and respiration by about 50 %, and fungal biomass by 23 %. In testate amoebae,
      rain exclusion decreased the density of live cells by 91 % and caused a shift in
      species composition at each of the altitudes studied, with ergosterol
      concentrations, microbial biomass, and water content explaining 25 % of the
      variation in species data. The results document that reduced precipitation
      negatively affects soil microorganisms, but that the response of testate amoebae
      markedly exceeds that of bacteria and fungi. This suggests that, in addition to
      food, low precipitation directly affects the community structure of testate
      amoebae, with the effect being more pronounced at lower altitudes. Overall, the
      results show that microorganisms and testate amoebae rapidly respond to a
      reduction in precipitation, with testate amoebae-representatives of higher
      trophic levels-being more sensitive. The results imply that precipitation and
      soil moisture in tropical rainforests are the main factors regulating
      decomposition and nutrient turnover.

PMID- 22614264
TI  - Inter-regional competition and quality in hospital care.
AB  - This study analyzes the effect of episode-of-care payment and patient choice on
      waiting time and the comprehensive quality of hospital care. The study assumes
      that two hospitals are located in two cities with different population sizes and
      compete with each other. We find that the comprehensive quality of hospital care
      as well as waiting time of both hospitals improve with an increase in payment per
      episode of care. However, we also find that the extent of these improvements
      differs according to the population size of the cities where the hospitals are
      located. Under the realistic assumptions that hospitals involve significant labor
      intensive work, we find the improvements in comprehensive quality and waiting
      time in a hospital located in a small city to be greater than those in a hospital
      located in a large city. The result implies that regional disparity in the
      quality of hospital care decreases with an increase in payment per episode of
      care.

PMID- 22614265
TI  - Increase in paravertebral muscle activity in lumbar kyphosis patients by surface
      electromyography compared with lumbar spinal canal stenosis patients and healthy
      volunteers.
AB  - STUDY DESIGN: Paravertebral muscle activity measurement by surface
      electromyography (EMG) in lumbar degenerative patients and healthy volunteers.
      OBJECTIVE: Muscle activity was tested in the standing position, and the influence
      of low back pain and alignment of the lumbar spine was assessed in the patients
      with lumbar kyphosis (LDK) or canal stenosis. SUMMARY OF BACKGROUND DATA: The
      number of kyphosis patients has increased as the population has grown older.
      Advanced kyphosis can cause difficulties in maintaining a standing position and
      affect daily living activities. The most direct cause is the atrophy of erector
      spinae muscles. The activity of these muscles has not yet been sufficiently
      evaluated and needs to be assessed objectively for the purpose of diagnosis and
      treatment. METHODS: The subjects were kyphosis patients who were 60 years of age
      or older, age-matched lumbar spinal canal stenosis patients, and healthy
      volunteers. Muscular activity at the L1-L2 and the L4-L5 intervertebral areas was
      recorded by surface EMG in the resting standing position and also with a weight
      load held in the standing position. Muscle activity and muscle fatigue, and the
      association between the Visual Analogue Scale, the Japanese Orthopaedic
      Association score for low back pain, and muscle activity, were analyzed. RESULTS:
      Kyphosis patients had a greater muscle activity in the lower back in the resting
      standing position and more severe muscle fatigue at the upper lumbar spine in
      comparison with patients with lumbar spinal canal stenosis. There was no
      association between muscle activity and clinical findings in patients with LDK
      although. CONCLUSIONS: Our study revealed the constant activity of paravertebral
      muscles and the susceptibility to muscle fatigue in patients with LDK. The
      quantification of muscle activity by surface EMG may show the pathology of LDK,
      and the decrease in muscle activity in the standing position may be a potentially
      useful index for guiding treatment.

PMID- 22614266
TI  - Comparison of the clinical outcome in overweight or obese patients after
      minimally invasive versus open transforaminal lumbar interbody fusion.
AB  - STUDY DESIGN: This is a prospective single-center nonrandomized control clinical
      study involving 81 overweight or obese patients who underwent minimally invasive
      or open transforaminal lumbar interbody fusion (TLIF). OBJECTIVE: The objective
      of this study was to evaluate the safety and efficacy of minimally invasive TLIF
      as an alternative technique in overweight or obese patients. SUMMARY OF
      BACKGROUND DATA: Spinal surgery in obese patients is associated with increased
      complications, blood loss, and operative times. The potential benefits of
      minimally invasive lumbar surgery in obese patients have been discussed in a few
      studies. However, there have been no prospective clinical reports published on
      the comparison of minimally invasive or open TLIF (OTLIF) in obese patients.
      METHODS: Eighty-one patients, 25 male and 56 female, with an average age of 55.3
      years (43-81 y) were prospectively evaluated. The main inclusion criterion was a
      body mass index >=25. The mean body mass index was 28.9+/-3.2. All patients
      suffering from lumbar canal stenosis (n=43), spondylolisthesis (n=29), or
      postlaminectomy instability (n=9) underwent 1-level minimally invasive TLIF
      (MiTLIF, n=43) or OTLIF (n=39). The following data were compared between 2
      groups: operative time, blood loss, x-ray exposure time, clinical and
      radiographic outcomes, and perioperative complications. The clinical outcome was
      assessed using the visual analogue scale and the Oswestry Disability Index (ODI).
      Radiographic evaluation of the lumbar spine was performed at 12 months
      postoperatively. RESULTS: In comparison with the OTLIF group, the MiTLIF group
      had significantly less operating time, less blood loss, and less postoperative
      back pain. The radiation time was significantly longer in the MiTLIF group. The
      clinical outcomes (Oswestry Disability Index scores) were basically identical in
      the 2 groups. Radiographic evaluation showed satisfactory bony union at the fixed
      level in both the MiTLIF group (42/43 cases) and the OTLIF group (38/39 cases).
      Overall complication rates were slightly higher in the OTLIF group, with 17.9% of
      overweight or obese patients having perioperative complications. CONCLUSIONS:
      MiTLIF is a safe and reliable procedure for treatment of overweight or obese
      patients. The minimally invasive technique offers several potential advantages
      when compared with the open procedure. Although this technique needs a longer x
      ray exposure time, it may still be a good option for overweight or obese
      patients.

PMID- 22614267
TI  - Indications and limitations of conservative treatment for pyogenic spondylitis.
AB  - STUDY DESIGN: Retrospective comparative study. OBJECTIVE: To elucidate the
      indications and limitations of conservative treatment for pyogenic spondylitis
      (PS). SUMMARY OF BACKGROUND DATA: The optimal strategy for treating PS,
      conservative or surgical, remains controversial. METHODS: Sixty-eight consecutive
      patients (44 males, 24 females; 62.6+/-13.8 y) suffering from PS were enrolled.
      Forty-three were successfully treated with conservative therapy including
      immobilization and administration of antibiotics [conservative treatment success
      (CTS) group]. Twenty-five patients underwent surgical intervention because of
      ineffective conservative treatment [conservative treatment failure (CTF) group].
      Clinical parameters such as duration of symptoms, C-reactive protein (CRP) at
      admission, durations of hospital stay, and Frankel score, and radiologic
      parameters such as the presence of epidural abscess, were investigated in both
      groups. RESULTS: The duration of symptoms, CRP at admission, and the duration of
      hospital stay were 1.72+/-1.02 months, 5.89+/-6.29 mg/dL, and 85.7+/-46.0 days,
      respectively, in the CTS group compared with 7.92+/-16.9 months, 2.22+/-3.08
      mg/dL, and 95.0+/-28.0 days in the CTF group. Differences were significant. At
      follow-up, 100% of the CTS group and 84% of the CTF group were ambulatory. A
      total of 86.1% of the CTS group lesions occurred at the lumbosacral region,
      whereas the majority (52%) of those in the CTF group were in the thoracic region.
      The incidence of epidural abscess was higher in the CTF group (84.0%) than in the
      CTS group (30.2%), and their greatest likelihoods were at the cervical/thoracic
      regions and lumbosacral region, respectively. CONCLUSIONS: The early phase of PS,
      in which the duration of disease between onset and admission was short and CRP at
      admission was active, was a good indication for conservative treatment regardless
      of the sites if there was neither paralysis nor worsening of kyphosis, and can
      even be an option for cases with mild paralysis due to epidural abscess occurring
      at the lumbosacral region.

PMID- 22614268
TI  - Comparison of screw malposition and vertebral artery injury of C2 pedicle and
      transarticular screws: meta-analysis and review of the literature.
AB  - STUDY DESIGN: Literature review and meta-analysis. OBJECTIVES: To compare the
      incidence of screw malposition and vertebral artery injury (VAI) with
      transarticular screws (TAS) and C2 pedicle screws (C2PS) using meta-analysis
      techniques. SUMMARY OF BACKGROUND DATA: Posterior instrumentation for
      atlantoaxial fusions can be challenging and risky. Some centers report a higher
      incidence of VAI with the implantation of TAS compared with C2PS, whereas other
      data do not support this. METHODS: Online databases were searched for English
      language articles between 1994 and April 2011 describing the clinical and
      radiographic outcomes after insertion of C2PS or TAS. Forty-one studies reporting
      on 3627 TAS and 33 studies describing 2979 C2PS met inclusion criteria for VAI or
      clinically significant misplacements (VAI, neurological deficits, or
      misplacements requiring surgical revision), and 36 studies reporting on 3280 TAS
      and 28 studies describing 2532 C2PS met inclusion criteria for radiographic
      misplacement outcomes. RESULTS: All studies comprised class III evidence. VAI
      occurred in 26 of 3627 (0.72%) implanted TAS and in 10 of 2979 (0.34%) implanted
      C2PS (P=0.01). Clinically significant misplacements occurred in 67 TAS (1.84%)
      and in 10 C2PS (0.34%; P<0.0001). The point estimate of VAI for TAS was 1.68%
      [confidence interval (CI), 1.23%-2.29%] and was higher than C2PS (1.09%; CI,
      0.73%-1.63%; P=0.01). The point estimate of clinically significant screw
      malposition for TAS was 2.33% (CI, 1.61%-3.37%) and was higher than that of C2PS
      (1.15%; CI, 0.77%-1.70%; P<0.001). CONCLUSIONS: With training, experience, and
      anatomic knowledge, both TAS and C2PS can be inserted accurately and safely.
      However, improper insertion and VAI can have catastrophic consequences. Our
      review identified a higher risk of VAI, neurological injury, and clinically
      significant malpositions with TAS compared with C2PS. These data provide
      preliminary support for the supposition that C2PS have a lower risk of morbidity.

PMID- 22614269
TI  - Body Mass Index as an Indicator of Pulmonary Dysfunction in Patients With
      Adolescent Idiopathic Scoliosis.
AB  - STUDY DESIGN: Prospective clinical study. OBJECTIVES: To investigate the factors
      correlated with pulmonary function in adolescent idiopathic scoliosis (AIS)
      patients, and to determine the influence of body mass index (BMI) on the
      pulmonary function. SUMMARY OF BACKGROUND DATA: Impaired pulmonary function has
      been reported in patients with AIS. The factors reported to affect pulmonary
      function included the curve magnitude, location of the apex vertebrae, decrease
      in thoracic kyphosis, and the number of vertebrae involved. A low BMI has been
      well confirmed in AIS patients. However, the relationship between BMI and
      pulmonary function has never been investigated. METHODS: One hundred twenty
      female patients with a single thoracic curve were enrolled in this study.
      Pulmonary function test and radiographic examination were performed. Several
      radiographic parameters, including the curve magnitude, the curve type, location
      of the apical vertebra, the number of vertebrae involved, and the degree of
      thoracic kyphosis, were recorded. BMI was calculated according to the
      measurements of standing height and body weight. Patients were divided into 2
      groups according to BMI, (group A >17.5 kg/cm and group B <=17.5 kg/cm), and the
      pulmonary function was compared between the 2 groups with students t test.
      Partial correlation analysis and stepwise multiple regression analysis were used
      to assess the association between BMI and the results of the pulmonary function
      test. The receiver operating characteristics curve was created to identify the
      best dividing point for diagnostic variables. RESULTS: The average percentage of
      predicted vital capacity, forced vital capacity, and forced expiratory volume in
      1 second was significantly decreased in patients with a lower BMI. A positive
      correlation was found between BMI and pulmonary function (r=0.41, P<0.001). The
      stepwise regression analysis showed that low BMI was significantly associated
      with pulmonary function impairment (R=0.206, P<0.001). According to the receiver
      operating characteristics curve, patients with a BMI <17.7 kg/cm are prone to
      have abnormal pulmonary function. CONCLUSIONS: BMI was found to be an important
      indicator for pulmonary function in AIS patients. The decreased BMI could explain
      approximately one-fifth of the variation in pulmonary impairment in AIS patients,
      which might shed some light on the rehabilitation of preoperative pulmonary
      function.

PMID- 22614270
TI  - Bicortical versus unicortical pedicle screws in direct vertebral rotation: an in
      vitro experimental study.
AB  - STUDY DESIGN: In vitro experimental study. OBJECTIVE: This study aimed to
      evaluate the biomechanical properties of bicortically placed and laterally
      oriented screws, which may represent an alternative approach for challenging
      sites during direct vertebral rotation (DVR). SUMMARY OF BACKGROUND DATA: DVR
      corrects the transverse plane deformity and the thoracic hump in idiopathic
      scoliosis. However, instrumentation of the convex side of the scoliosis apex may
      pose a challenge, not allowing the placement of suitable sized screws in adequate
      direction. METHODS: Forty-eight calf vertebrae were used and each vertebral body
      was instrumented with 1 pedicle screw as follows: unicortical group (n=16), a
      short screw was unicortically placed and directed laterally; bicortical group
      (n=16), a short screw was bicortically placed again in lateral direction; control
      group (n=16), a screw with ideal length and direction was placed. Vertebral
      bodies were rigidly anchored in a custom device. Each screw was rotated using a
      constant length lever arm while collecting "force to failure" data. RESULTS:
      Significantly better results were obtained with bicortical screwing when compared
      with unicortical screwing (335.4+/-45.6 vs. 239.5+/-58.50 N, P<0.001). However,
      mean "force to failure" was significantly higher in the controls than in the
      bicortical group (415.8+/-49.2 vs. 335.4+/-45.6 N, P<0.001). CONCLUSIONS:
      Bicortical screw placement may provide a biomechanically superior construct than
      unicortical screw placement for resisting DVR maneuver during scoliosis
      correction. This technique may represent an effective and safe approach,
      particularly for the convex side of the scoliosis apex, with increased resistance
      to derotational forces and decreased risk of bone failure. Further clinical
      studies are warranted for firmer conclusions.

PMID- 22614271
TI  - Single- and double-SSR primer  combined analyses in rice.
AB  - Polymerase  chain reaction (PCR) is the foundation of SSR molecular marker
      technology. We  used sib rice varieties J518, XD1 and SD23 as experimental
      materials, selecting  30 pairs of SSR primers, including RM127, RM337 and RM5172,
      covering the rice  genome, and performed single- and double-SSR primer combined
      analyses. We found  that under the same PCR system and conditions, a single
      primer of the SSR  primer pairs could amplify the same fragments as double
      primers do. The  sequencing results demonstrated that some amplified fragments
      that we  previously believed to come from double primers were actually produced
      by a  single primer. The use of this kind of primer, such as the RM127 primer
      pair,  for marker-assisted breeding will therefore be misleading. Additionally,
      using  the same PCR system and conditions, some single primers that are part of
      SSR  primer pairs can amplify many more specific fragments than double-SSR
      primers.  For instance, in the case of the RM5172 primer pair, a single primer P1
      amplified approximately three times the number of fragments as the double 
      primer. This information can contribute to research on genetic diversity of 
      species, understanding of genetic relationships and identification of germplasm 
      resources. Accordingly, combined analyses of single- and double-primer 
      amplification products not only can remove single-primer amplification  fragments
      and false-positives from double-primer amplification products in  order to
      improve test accuracy, but also can facilitate research on genetic  diversity,
      exploration of phylogenetic relationships and identification of  germplasm
      resources. We define this method as "single- and double-SSR primer  combined
      analyses".

PMID- 22614272
TI  - Detection of Y chromosome microdeletions and mitochondrial DNA mutations  in 
      male infertility patients.
AB  - Infertility affects about 10-15% of all couples  attempting pregnancy with
      infertility attributed to the male partner in  approximately half of the cases.
      Proposed causes of male infertility include  sperm motility disturbances, Y
      chromosome microdeletions, chromosomal  abnormalities, single gene mutations, and
      sperm mitochondrial DNA (mtDNA)  rearrangements. To investigate the etiology of
      decreased sperm fertility and  motility of sperm and to develop an appropriate
      therapeutic strategy, the  molecular basis of these defects must be elucidated.
      In this study, we aimed to  reveal the relationships between the genetic factors
      including sperm mtDNA  mutations, Y chromosome microdeletions, and sperm
      parameters that can be  regarded as candidate factors for male infertility.
      Thirty men with a history  of infertility and 30 fertile men were recruited to
      the study. Y chromosome  microdeletions were analyzed by multiplex PCR.
      Mitochondrial genes ATPase6, Cytb, and ND1, were amplified by PCR and then
      analyzed by direct  sequencing. No Y chromosome microdeletions were detected in
      either group.  However, a total of 38 different nucleotide substitutions were
      identified in  the examined mitochondrial genes in both groups, all of which are
      statistically  non-significant. Fifteen substitutions caused an amino acid change
      and 12 were  considered novel mutations. As a conclusion, mtDNA mutations and Y
      chromosome  microdeletions in male infertility should be examined in larger
      numbers in  order to clarify the effect of genetic factors.

PMID- 22614273
TI  - DNA isolation protocol for the medicinal plant lemon  balm (Melissa officinalis,
      Lamiaceae).
AB  - Lemon balm (Melissa officinalis) is a medicinal  plant that is widely used as a
      sedative or calmant, spasmolytic and  antibacterial agent and sleep aid. This has
      led to a high demand for lemon balm  products, resulting in the extinction of
      this species in some of its natural  habitats. Molecular techniques have
      increasingly been used in plant diversity  conservation and isolation of PCR
      amplifiable genomic DNA is an important  pre-requisite. Lemon balm contains high
      levels of polyphenols and  polysaccharides, which pose a major challenge for the
      isolation of high-quality  DNA. We compared different genomic DNA extraction
      protocols, including  traditional phenol-chloroform DNA extraction protocols and
      two commercial kits  for DNA purification for their ability to produce good
      quality DNA from fresh  leaves of five lemon balm genotypes. Quality and quantity
      of the DNA samples  were determined using 0.8% agarose gel electrophoresis and a
      spectrophotometer.  The DNA purity was further confirmed by PCR amplification
      using barley  retrotransposon LTR base primers. The spectral quality of DNA as
      measured by  the A(260)/A(280) ratio ranged from 1.46 to 2.37. The Fermentase
      genomic  DNA purification kit and the CTAB extraction protocol using PVP and
      ammonium  acetate to overcome the high levels of polyphenols and polysaccharides
      yielded  high-quality DNA with a mean A(260)/A(280) ratio of 1.87. The quantity
      of DNA and its PCR purity  were similar with all the protocols, but considering
      the time and cost required  for extraction of DNA from a large number of samples,
      the CTAB protocol using  PVP and ammonium acetate is suitable for lemon balm.

PMID- 22614274
TI  - Association between CSN3 and BCO2 gene  polymorphisms and milk performance traits
      in the Czech Fleckvieh cattle breed.
AB  - Daily milk, fat and protein yield and amount of somatic cells in cow milk are
      very important factors that influence milk performance traits. An association
      between polymorphisms in the kappa casein (CSN3) gene and milk production,
      composition and technical properties has been previously reported; however, this
      type of information is not available for the bovine beta-carotene oxygenase 2
      (BCO2) gene--the BCO2 gene has relationship with milk color and meat fat color,
      which is dependent on content of beta-carotene. We analyzed these two genes and
      their relationship with milk performance traits (daily milk, fat and protein
      yield, somatic cell count, SCC) in one cattle population, Czech Fleckvieh (N =
      152). All animals were milked twice a day and kept in the same environmental
      conditions. The Fleckvieh is a typical Czech cattle breed farming for milk and
      meat production. It is the most common breed in the Czech Republic. DNA was
      isolated from milk or from hairs. Genes were analyzed using PCR-RFLP, frequencies
      of alleles and genotypes were calculated and association analysis was performed
      using a GLM Procedure in SAS. Statistical analysis established that the CSN3 gene
      has no statistically significant influence on daily milk, fat and protein yield
      and SCC. Compared to other references this result can be explained by, e.g.,
      small group of animals and different cattle breed. The BCO2 gene (genotypes AA
      and AG) shows a statistically significant relationship (P = 0.05) with daily
      milk, protein yield and SCC.

PMID- 22614275
TI  - Mitochondrial D-loop nucleotide diversity in Astyanax (Osteichthyes, Characidae)
      from the upper Parana and upper Paraguay River basins.
AB  - The morphological discrimination between the species Astyanax  altiparanae and A.
      asuncionensis of the upper Parana River and  Paraguay River basins, respectively,
      has always been difficult. Two D-loop  haplogroups of A. altiparanae are known,
      one with the presence (AltoPR)  or the absence (AltoPR-D) of a 32-bp block
      similar to that in A.  asuncionensis. We examined these samples to characterize
      A. altiparanae and  verify whether A. asuncionensis occurred in the upper Parana
      River prior  to the submergence of the Sete Quedas Falls when Itaipu reservoir
      was  impounded. D-loop sequences were analyzed in A. altiparanae of the upper 
      Parana and Iguacu Rivers and those of A. asuncionensis of the upper  Paraguay
      River. The haplogroup AltoPR was found at all sites of the upper  Parana and
      Iguacu Rivers, whereas AltoPR-D occurred in the Itaipu reservoir,  floodplain and
      in the Tiete and Grande Rivers. Two haplogroups of A.  asuncionensis were
      identified and both did not have the 32-bp block.  However, AltoPR and AltoPR-D
      differed from one another in 5.1% of their bases  and between 8.9 and 12.5% with
      regard to the haplogroups of the upper Paraguay  basin. Further, AltoPR-D
      occurred in the Grande River upstream the Marimbondo  Falls and other older
      reservoirs than Itaipu. The results reject the hypothesis  of the establishment
      of A. asuncionensis and suggest that the haplogroup  AltoPR-D existed in the
      upper Parana River before the impounding of the Itaipu  reservoir. Moreover,
      morphological similarity and high genetic variation within  the
      altiparanae/asuncionensis group suggest the existence of a  cryptic species
      complex.

PMID- 22614276
TI  - R620W functional polymorphism of protein tyrosine phosphatase  non-receptor type
      22 is not associated with pulmonary tuberculosis  in Zahedan, southeast Iran.
AB  - The protein tyrosine phosphatase non-receptor type 22  (PTPN22) gene, which
      encodes an intracellular lymphoid-specific phosphatase, is  considered an
      important regulator of T-cell activation. We investigated a  possible association
      between the PTPN22 C1858T (R620W) polymorphism and  pulmonary tuberculosis in an
      Iranian population. Single nucleotide  polymorphisms of PTPN22 C1858T (rs2476601)
      were genotyped in 172 pulmonary  tuberculosis cases and 204 normal subjects from
      Zaheden, Iran. Frequencies of  genotypes CC, CT and TT of the PTPN22 C1858T
      polymorphism were 98.3, 1.7 and 0%  in the pulmonary tuberculosis patients, and
      96.1, 3.9 and 0% in the control  group, respectively (P = 0.239). The frequency
      of the minor (T) allele was 0.8%  in pulmonary tuberculosis patients and 2.0% in
      controls. Significant  differences were not observed in genotype or allele
      frequencies of PTPN22  C1858T in the comparison between pulmonary tuberculosis
      patients and healthy  subjects in our Iranian population sample.

PMID- 22614277
TI  - Arylamine  N-acetyltransferase 2 genotypes in a Mexican population.
AB  - The acetylating activity of N-acetyltransferase 2  (NAT2) has critical
      implications for therapeutics and disease susceptibility.  To date, several
      polymorphisms that alter the enzymatic activity and/or protein  stability of NAT2
      have been identified. We examined the distribution and  frequency of NAT2
      genotypes in the Mexican population. Among 250 samples  amplified and sequenced
      for the NAT2 gene, we found seven different  SNPs; the most frequent allele was
      803 A>G (35.8%), followed by 282 C>T,  341 T>C, and 481 C>T. There were no
      differences in the distribution of  SNPs between healthy subjects and cancer
      patients. These eight polymorphisms  defined 26 diplotypes; 11.6% were wild type
      (NAT2*4/NAT2*4), while the  most common diplotype was NAT2*4/NAT2*5B, present in
      17.2%. We did not  identify other common polymorphisms. The results were compared
      with the NAT2 SNPs reported from other populations. All but the Turkish
      population was  significantly different from ours. We conclude that the mixed
      race Mexican  population requires special attention because NAT2 genotype
      frequencies  differ from those in other regions of the world.

PMID- 22614278
TI  - New microsatellite markers for bananas (Musa spp).
AB  - Thirty-four microsatellite markers (SSRs) were  identified in EST and BAC clones
      from Musa acuminata burmannicoides var.  Calcutta 4 and validated in 22 Musa
      genotypes from the Banana Germplasm  Bank of Embrapa-CNPMF, which includes wild
      and improved diploids. The number of  alleles per locus ranged from 2 to 14. The
      markers were considered highly informative  based on their polymorphism
      information content values; more than 50% were  above 0.5. These SSRs will be
      useful for banana breeding programs, for studies  of genetic diversity, germplasm
      characterization and selection, development of  saturated genetic linkage maps,
      and marker assisted selection.

PMID- 22614279
TI  - Differences in H3K4 trimethylation in in vivo and in vitro fertilization mouse
      preimplantation embryos.
AB  - Trimethylation of lysine 4 at histone 3 (H3K4me3) is  considered a marker of
      active transcription; it plays an important role in  transcription reprogramming
      efficiency. We compared the levels of H3K4me3 in mouse  preimplantation embryos
      from MII stage oocytes produced by in vivo and in  vitro fertilization (IVF)
      using immunofluorescence histochemistry. IVF  embryos were further treated with
      trichostatin A (a histione deacetylase  inhibitor) to investigate the effect of
      histone acetylation on H3K4me3. We  found higher levels of H3K4me3 in MII stage
      oocytes in metaphase chromosomes.  The pattern of H3K4 trimethylation of in vivo
      embryos from zygote to  blastocyst stages was similar to that of IVF embryos;
      however, the  concentration of H3K4me3 was significantly higher in the in vivo
      fertilization  embryos. The levels of H3K4me3 in the trichostatin A-treated
      groups were also  significantly increased. We conclude that culture condition and
      environmental  changes can cause histone modification and that the effect of
      these  environmental conditions on epigenetic changes should be taken into 
      consideration.

PMID- 22614281
TI  - Event-specific qualitative and  quantitative PCR detection of the GMO carnation
      (Dianthus caryophyllus)  variety Moonlite based upon the 5'-transgene integration
      sequence.
AB  - To ensure the implementation of genetically modified organism (GMO)-labeling
      regulations, an event-specific detection method was developed based on the
      junction sequence of an exogenous integrant in the transgenic carnation variety
      Moonlite. The 5'-transgene integration sequence was isolated by thermal
      asymmetric interlaced PCR. Based upon the 5'-transgene integration sequence, the
      event-specific primers and TaqMan probe were designed to amplify the fragments,
      which spanned the exogenous DNA and carnation genomic DNA. Qualitative and
      quantitative PCR assays were developed employing the designed primers and probe.
      The detection limit of the qualitative PCR assay was 0.05% for Moonlite in 100 ng
      total carnation genomic DNA, corresponding to about 79 copies of the carnation
      haploid genome; the limit of detection and quantification of the quantitative PCR
      assay were estimated to be 38 and 190 copies of haploid carnation genomic DNA,
      respectively. Carnation samples with different contents of genetically modified
      components were quantified and the bias between the observed and true values of
      three samples were lower than the acceptance criterion (<25%) of the GMO
      detection method. These results indicated that these event-specific methods would
      be useful for the identification and quantification of the GMO carnation
      Moonlite.

PMID- 22614280
TI  - DNA sequence variants in the carbonyl reductase 1 (cbr1) gene in seven breeds of
      Canis lupus familiaris.
AB  - The anticancer anthracyclines doxorubicin and daunorubicin  are used to treat a
      variety of cancers in dogs. The therapeutic utility of  anthracyclines is limited
      by cardiotoxicity in some cases. Synthesis of  anthracycline alcohol metabolites
      by carbonyl reductase 1 (CBR1) is crucial for  the pathogenesis of
      cardiotoxicity. We hypothesize that genetic polymorphisms  in canine cbr1
      contribute to the variable pharmacodynamics of  anthracyclines in dogs. DNA
      sequence variants in canine cbr1 were  investigated in DNA samples from dogs of
      seven breeds. Thirteen SNPs were  detected in canine cbr1. A 10-bp deletion in
      the 5'-untranslated region  (5'-UTR) was found in specimens from the Labrador
      Retriever, Beagle, Siberian  Husky, and Boxer breeds. The 5'-UTR also included a
      polymorphic "hot spot"  region immediately downstream of the 10-bp deletion. DNA
      sequence variants in  the "hot spot region" ranged from 1 to 21 bp in length.
      Bioinformatics searches  identified a cluster of three to six potential binding
      sites for the  transcription factor Sp1 in the DNA segment containing both the
      "hot spot"  region and the 10-bp deletion. This information provides a foundation
      to allow  us to investigate whether DNA sequence variants in the 5'-UTR of canine
      cbr1 impact the pharmacodynamics of anticancer anthracyclines in dogs.

PMID- 22614282
TI  - Phylogenetic relationship of  Turkish Apis mellifera subspecies based on
      sequencing of mitochondrial  cytochrome C oxidase I region.
AB  - Mitochondrial  DNA sequence variation can be used to infer honey bee evolutionary
      relationships. We examined DNA sequence diversity in the cytochrome C oxidase I 
      (COI or Cox1) gene segment of the mitochondrial genome in 112 samples of Apis
      mellifera from 15 different populations in Turkey. Six novel haplotypes  were
      found for the COI gene segment. There were eight variable sites in the COI  gene,
      although only three were parsimony-informative sites. The mean pairwise  genetic
      distance was 0.3% for the COI gene segment. Neighbor-joining (NJ) trees  of the
      COI gene segment were constructed with the published sequences of A.  mellifera
      haplotypes that are available in GenBank; the genetic variation  was compared
      among the different honeybee haplotypes. The NJ dendogram based on  the COI
      sequences available in GenBank showed that Eastern European races were  clustered
      together, whereas the Mellifera and Iberian haplotypes were clustered  far apart.
      The haplotypes found in this study were clustered together with A.  mellifera
      ligustica and some of the Greek honey bees (accession Nos.  GU056169 and
      GU056170) found in NCBI GenBank database. This study expands the  knowledge about
      the mitochondrial COI region and presents the first  comprehensive sequence
      analysis of this region in Turkish honeybees.

PMID- 22614283
TI  - Cytoplasmic and extracellular expression of  pharmaceutical-grade mycobacterial
      65-kDa heat shock protein in Lactococcus  lactis.
AB  - Lactic acid bacteria (LAB) are an attractive and safe  alternative for the
      expression of heterologous proteins, as they are  nonpathogenic and endotoxin
      free organisms. Lactococcus lactis, the LAB  model organism, has been extensively
      employed in the biotechnology field for  large-scale production of heterologous
      proteins, and its use as a "cell  factory" has been widely studied. We have been
      particularly interested in the  use of L. lactis for production of heat shock
      proteins (HSPs), which  reportedly play important roles in the initiation of
      innate and adaptive immune  responses. However, this activity has been
      questioned, as LPS contamination  appears to be responsible for most, if not all,
      immunostimulatory activity of  HSPs. In order to study the effect of pure HSPs on
      the immune system, we  constructed recombinant L. lactis strains able to produce
      and properly  address the Mycobacterium leprae 65-kDa HSP (Hsp65) to the
      cytoplasm or  to the extracellular medium, using a xylose-induced expression
      system. Approximately  7 mg/L recombinant Hsp65 was secreted. Degradation
      products related to  lactococcal HtrA activity were not observed, and the Limulus
      amebocyte lysate  assay demonstrated that the amount of LPS in the recombinant
      Hsp65 preparations  was 10-100 times lower than the permitted levels established
      by the U.S. Food  and Drug Administration. These new L. lactis strains will allow
      investigation of the effects of M. leprae Hsp65 without the interference  of
      LPS; consequently, they have potential for a variety of biotechnological, 
      medical and therapeutic applications.

PMID- 22614284
TI  - A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis
      as a previously unknown mechanism of cytotoxic action for taxoids.
AB  - The design, synthesis and biological evaluation of a novel C,D-spirolactone
      analogue of paclitaxel is described. This is the first paclitaxel analogue
      without an oxetane D-ring that shows a significant cytotoxic effect (activity one
      order of magnitude lower than paclitaxel). More importantly, its cytotoxicity is
      a result of a different mechanism of action, involving mTOR inhibition-dependent
      autophagy instead of G(2)/M cell cycle arrest-dependent apoptosis.

PMID- 22614285
TI  - Effectiveness of intravesical hyaluronic acid/chondroitin sulfate in recurrent
      bacterial cystitis: a randomized study.
AB  - INTRODUCTION AND HYPOTHESIS: The glycosaminoglycan hyaluronic acid (HA) protects
      the urothelium; damage may increase bacterial adherence and infection risk. This
      study evaluated the effect of intravesical HA in recurrent bacterial cystitis
      (RBC). METHODS: Women with RBC were randomized to intravesical HA 800 mg and
      chondroitin sulfate (CS) 1 g (IALURIL, IBSA) in 50 mL of saline solution once
      weekly for 4 weeks then once every 2 weeks twice more (group 1) or long term
      antibiotic prophylaxis using sulfamethoxazole 200 mg and trimethoprim 40 mg once
      weekly for 6 weeks (group 2; control). Evaluations included: cystitis recurrence
      at 2 and 12 months; subjective pain symptoms (visual analog scale [VAS]); 3 day
      voiding; sexual function; quality of life (King's Health Questionnaire [KHQ]);
      frequency symptoms/frequency symptoms (PUF symptom scale); and maximum
      cystometric capacity (MCC). Means +/- standard deviations were reported, with
      Mann-Whitney test for between-group comparison (significance P < .05). RESULTS:
      Of 28 women (mean age 60 +/- 13 y) randomized, 26 completed follow-up (mean
      follow-up 11.5 mo). Group 1 showed a significant improvement in all evaluations;
      cystitis recurrence (1 +/- 1.2 versus 2.3 +/- 1.4, P = .02); 3-day voiding (mean
      17.8 +/- 3.5 vs 24.2 +/- 8.3, P = .04); symptom VAS (1.6 +/- 0.8 vs 7.8 +/- 1.6,
      P < .001); PUF score (11.2 +/- 2.7 vs 19.6 +/- 2.2, P < .001), KHQ score (18.4 +/
      7.2 vs 47.3 +/- 13.6, P < .001), and MCC (380 +/- 78 vs 229 +/- 51 mL, P < .001)
      vs group 2 at 12 mo. No adverse effects were recorded. CONCLUSIONS: Intravesical
      HA and CS in combination significantly reduced cystitis recurrence and improved
      urinary symptoms, quality of life, and cystometric capacity in RBC patients at 12
      mo follow-up versus antibiotic prophylaxis. Study limitations include a small
      sample and relatively short follow-up.

PMID- 22614286
TI  - Endoscopic closure of iatrogenic gastrointestinal tract perforations with the
      over-the-scope clip.
AB  - BACKGROUND: Newer techniques such as mucosal resection, submucosal dissection and
      risky polypectomy will probably lead to increasing numbers of iatrogenic
      perforations. Reliable immediate closure of these lesions would increase safety
      and acceptance of the interventions. METHODS: All acute directly observed
      perforations during diagnostic or therapeutic endoscopy were treated by the
      application of an over-the-scope clip. All consecutive patients from 2009 to
      August 2011 were followed in our tertiary referral center. The main outcome was
      technically successful closure of the perforation during endoscopy with a
      subsequent clinical observation for 24 h. RESULTS: During the observation period,
      acute perforation occurred in 14 patients. All but 1 patient had technically
      successful treatment. Due to persistent abdominal pain, 3 patients had to be sent
      to the theater for laparoscopic evaluation after colon perforation. These 3
      lesions were proven to be sealed and no resection of the colon was indicated. One
      patient with gastric adenocarcinoma had to be resected subtotally following
      endoscopic mucosal resection. Hospital stay ranged from 2 to 21 days. CONCLUSION:
      Directly observed perforations up to 30 mm diameter during endoscopy should be
      treated by deploying an over-the-scope clip. Endoscopists should be encouraged to
      be trained and to use over-the-scope clips in the stomach, duodenum and colon.

PMID- 22614287
TI  - Genome-wide significant associations in schizophrenia to ITIH3/4, CACNA1C and
      SDCCAG8, and extensive replication of associations reported by the Schizophrenia
      PGC.
AB  - The Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC)
      highlighted 81 single-nucleotide polymorphisms (SNPs) with moderate evidence for
      association to schizophrenia. After follow-up in independent samples, seven loci
      attained genome-wide significance (GWS), but multi-locus tests suggested some
      SNPs that did not do so represented true associations. We tested 78 of the 81
      SNPs in 2640 individuals with a clinical diagnosis of schizophrenia attending a
      clozapine clinic (CLOZUK), 2504 cases with a research diagnosis of bipolar
      disorder, and 2878 controls. In CLOZUK, we obtained significant replication to
      the PGC-associated allele for no fewer than 37 (47%) of the SNPs, including many
      prior GWS major histocompatibility complex (MHC) SNPs as well as 3/6 non-MHC SNPs
      for which we had data that were reported as GWS by the PGC. After combining the
      new schizophrenia data with those of the PGC, variants at three loci (ITIH3/4,
      CACNA1C and SDCCAG8) that had not previously been GWS in schizophrenia attained
      that level of support. In bipolar disorder, we also obtained significant evidence
      for association for 21% of the alleles that had been associated with
      schizophrenia in the PGC. Our study independently confirms association to three
      loci previously reported to be GWS in schizophrenia, and identifies the first GWS
      evidence in schizophrenia for a further three loci. Given the number of
      independent replications and the power of our sample, we estimate 98% (confidence
      interval (CI) 78-100%) of the original set of 78 SNPs represent true
      associations. We also provide strong evidence for overlap in genetic risk between
      schizophrenia and bipolar disorder.

PMID- 22614288
TI  - Brain white matter tract integrity as a neural foundation for general
      intelligence.
AB  - General intelligence is a robust predictor of important life outcomes, including
      educational and occupational attainment, successfully managing everyday life
      situations, good health and longevity. Some neuronal correlates of intelligence
      have been discovered, mainly indicating that larger cortices in widespread
      parieto-frontal brain networks and efficient neuronal information processing
      support higher intelligence. However, there is a lack of established associations
      between general intelligence and any basic structural brain parameters that have
      a clear functional meaning. Here, we provide evidence that lower brain-wide white
      matter tract integrity exerts a substantial negative effect on general
      intelligence through reduced information-processing speed. Structural brain
      magnetic resonance imaging scans were acquired from 420 older adults in their
      early 70s. Using quantitative tractography, we measured fractional anisotropy and
      two white matter integrity biomarkers that are novel to the study of
      intelligence: longitudinal relaxation time (T1) and magnetisation transfer ratio.
      Substantial correlations among 12 major white matter tracts studied allowed the
      extraction of three general factors of biomarker-specific brain-wide white matter
      tract integrity. Each was independently associated with general intelligence,
      together explaining 10% of the variance, and their effect was completely mediated
      by information-processing speed. Unlike most previously established
      neurostructural correlates of intelligence, these findings suggest a functionally
      plausible model of intelligence, where structurally intact axonal fibres across
      the brain provide the neuroanatomical infrastructure for fast information
      processing within widespread brain networks, supporting general intelligence.

PMID- 22614289
TI  - Brain structural changes as vulnerability factors and acquired signs of post
      earthquake stress.
AB  - Many survivors of severe disasters, even those without posttraumatic stress
      disorder (PTSD), need psychological support. To understand the pathogenesis of
      PTSD symptoms and prevent the development of PTSD, the critical issue is to
      distinguish neurological abnormalities as vulnerability factors from acquired
      signs of PTSD symptoms in the early stage of adaptation to the trauma in the
      normal population. The neurological underpinnings of PTSD have been well
      characterized, but the causal relationships with the traumatic event are still
      unclear. We examined 42 non-PTSD subjects to find brain morphometric changes
      related to the severity of PTSD symptoms in a longitudinal magnetic resonance
      imaging study extending through the Great East Japan Earthquake. We found that
      regional grey matter volume (rGMV) in the right ventral anterior cingulate cortex
      (ACC) before the earthquake, and decreased rGMV in the left orbitofrontal cortex
      (OFC) through the earthquake were negatively associated with PTSD symptoms. Our
      results indicate that subjects with smaller GMV in the ACC before the earthquake,
      and subjects with decreased GMV in the OFC through the earthquake were likely to
      have PTSD symptoms. As the ACC is involved in processing of fear and anxiety, our
      results indicate that these processing are related to vulnerability for PTSD
      symptoms. In addition, decreased OFC volume was induced by failing to extinct
      conditioned fear soon after the traumatic event. These findings provide a better
      understanding of posttraumatic responses in early stage of adaptation to the
      trauma and may contribute to the development of effective methods to prevent
      PTSD.

PMID- 22614290
TI  - Power in GWAS: lifting the curse of the clinical cut-off.

PMID- 22614291
TI  - A neurogenetics approach to understanding individual differences in brain,
      behavior, and risk for psychopathology.
AB  - Neurogenetics research has begun to advance our understanding of how genetic
      variation gives rise to individual differences in brain function, which, in turn,
      shapes behavior and risk for psychopathology. Despite these advancements,
      neurogenetics research is currently confronted by three major challenges: (1)
      conducting research on individual variables with small effects, (2) absence of
      detailed mechanisms, and (3) a need to translate findings toward greater clinical
      relevance. In this review, we showcase techniques and developments that address
      these challenges and highlight the benefits of a neurogenetics approach to
      understanding brain, behavior and psychopathology. To address the challenge of
      small effects, we explore approaches including incorporating the environment,
      modeling epistatic relationships and using multilocus profiles. To address the
      challenge of mechanism, we explore how non-human animal research, epigenetics
      research and genome-wide association studies can inform our mechanistic
      understanding of behaviorally relevant brain function. Finally, to address the
      challenge of clinical relevance, we examine how neurogenetics research can
      identify novel therapeutic targets and for whom treatments work best. By
      addressing these challenges, neurogenetics research is poised to exponentially
      increase our understanding of how genetic variation interacts with the
      environment to shape the brain, behavior and risk for psychopathology.

PMID- 22614292
TI  - The impact of CACNA1C allelic variation on effective connectivity during
      emotional processing in bipolar disorder.

PMID- 22614293
TI  - Autologous fat transfer for face rejuvenation with tumescent technique fat
      harvesting and saline washing: a report of 215 cases.
AB  - Various materials have been used for tissue augmentation and for the treatment of
      rhytids. Autologous fat transfer (AFT) is considered ideal regarding
      biocompatibility and patient concerns. This study was performed on a series of
      215 female patients for face rejuvenation with tumescent technique fat harvesting
      and saline washing. The study was based on two AFT procedures for each patient.
      Second treatment was performed at least 1 month after the first operation. Their
      mean age was 55.5+/-2.1 years. High-definition photographs in five standard
      views, front (n=1), side (n=2) and oblique of 3/4 (n=2), were taken for the
      preoperative morphological study. Aesthetic outcomes were evaluated by the
      operating surgeon, the patient and an independent dermatologist. Outcomes were
      evaluated by comparing the preoperative photographs with those taken 1 month
      after the first procedure and at the end of the 1-year follow-up period. At 12
      months all the patients except one noted an improvement. Of these 85.6% (184
      patients) were satisfied with the treatment. The operating surgeon and the
      independent observer noted respectively a sufficient correction in 88.8 and
      95.3%. AFT was considered painless by 94.9% and slightly painful by 5.1% of
      subjects. Fat tissue harvesting by tumescent anesthesia and purification with
      saline washing enable adipocyte viability to be preserved throughout the
      procedure and to perform the treatment under local anesthesia.

PMID- 22614294
TI  - [Burying our head in the sand will get us nowhere].

PMID- 22614295
TI  - [The price of war].

PMID- 22614296
TI  - Overweight in children--a rural problem?

PMID- 22614297
TI  - [Chronic fatigue syndrome and evolution].

PMID- 22614299
TI  - [Electromagnetic fields and the pregnancies].

PMID- 22614300
TI  - [Physicians' liability and insurance needs after the authorization has lapsed].

PMID- 22614301
TI  - [Lack of safety in medicine supply].

PMID- 22614302
TI  - [Collaboration in mental health care].

PMID- 22614303
TI  - [Psychopharmacologic outpatient clinics].

PMID- 22614304
TI  - The reality of war:  wounded and fallen Norwegian soldiers in Afghanistan.
AB  - BACKGROUND: Norway has been contributing military forces to Afghanistan since
      2001. The following is an overview of all combat-related injuries and deaths
      among Norwegian soldiers in the period from 2002 to 2010. MATERIAL AND METHOD:
      All medical records for Norwegian military personnel in Afghanistan in the period
      to January 2011 were reviewed and those who fell or were injured during combat
      were identified. The mechanism and anatomical region of the injury were
      registered and an injury severity score (ISS), revised trauma score (RTS) and
      probability of survival score were calculated. Deaths were classified according
      to military trauma terminology and were additionally assessed as either "non
      survivable" or "potentially survivable". RESULTS: There were 45 injury incidents
      with nine deaths among 42 soldiers. The injury mechanism behind seven of the
      deaths was an improvised explosive device (IED). All injuries resulting in deaths
      were "non-survivable". Seven soldiers were severely injured. The mechanisms were
      bullet wounds, IED, splinters from grenades and landmine explosions. Twenty nine
      incidents involving 28 soldiers resulted in minor injuries. The most frequent
      mechanism was ricochet or splinter injury from shooting or an exploding grenade.
      INTERPRETATION: The majority of conflict-related injuries in Afghanistan were due
      to explosions. The mechanism and anatomical distribution of the injuries was the
      same among Norwegian soldiers as among allies. The deaths were due to extensive
      injuries that were non-survivable.

PMID- 22614305
TI  - [Overweight children--how important is the urban/rural factor?].
AB  - BACKGROUND: Targeted measures to prevent overweight children are dependent on a
      knowledge of which environmental factors play a part. We wanted to investigate
      whether overweight in Norwegian eight-year-olds is related to whether they live
      in urban or rural areas. MATERIAL AND METHOD: In the cross-sectional study
      "Children's growth in Norway 2008", the weight, height and waist of 3473 eight
      year-olds were measured. We examined relationships between overweight and waist
      measurement and centrality, population density and number of inhabitants in the
      municipalities where the children lived by means of regression analyses. RESULT:
      In adjusted analyses, the odds on children in central municipalities being
      overweight was 34 lower than for children in less central municipalities (OR =
      0.66; 95 % CI: 0.46-0.94), and children in municipalities with a high population
      density had on average 0.66 cm smaller waists than children in municipalities
      with a low population density (95 % CI: 0.02-1.31). The relationships between
      overweight and the explanatory variables population density and number of
      inhabitants, and between waist measurement and the explanatory variables
      centrality and population density showed the same tendency, but were not
      statistically significant in the adjusted analyses. INTERPRETATION: The results
      indicate that there is a higher percentage of overweight children in rural areas
      than in urban areas. Education and income level in the municipalities appeared to
      explain some of the effect of the urbanity variables on overweight and waist
      measurement.

PMID- 22614306
TI  - [Increased use of antibiotics among nineteen-year-olds  in May].
AB  - BACKGROUND: The use of some drugs is significantly higher among 19-year-olds than
      among young people in adjacent age groups. We aimed to investigate the use of
      prescribed drugs in young people aged 17, 19 and 21 in order to identify trends
      in patterns of consumption. MATERIALS AND METHODS: Data were collected from the
      Norwegian Prescription Database 2005-2011. Prevalence (proportion of drug users)
      by gender, age (17, 19, 21 years), prescription date and county of residence are
      presented. Only drugs with more than 100 users per year in each age group (17,
      19, 21) were included. RESULTS: Use of some antibiotics and drugs for cough and
      eye infections was higher in 19-year-olds than in 17 and 21-year-olds. Moreover,
      the seasonal variation in the use of these drugs was different for 19-year-olds,
      with a marked peak in May and a lower winter peak than in the general population.
      The day-to-day prevalence showed a peak in the prescription rate just after the
      Norwegian Independence Day on 17 May. Girls had a higher consumption than boys.
      Considerable county variation was observed for 19-year-olds in the month of May.
      INTERPRETATION: The increased incidence of antibiotics, cough medicine and drugs
      used for eye infections in 19-year-olds compared with other young people can be
      explained by increased risk behaviour in the weeks before 17 May linked to
      graduation from Norwegian upper secondary schools. The findings give reason to
      warn against the present form of graduation celebrations which involve little
      sleep and all-night partying in close contact with others. They also give urgency
      to the question of whether to move the final examination period at upper
      secondary level away from the weeks immediately following 17 May.

PMID- 22614307
TI  - Drug use and breastfeeding.
AB  - BACKGROUND: This article describes the principles of drug transfer into breast
      milk and how drugs may affect breast-fed infants, and provides practical advice
      about what should be considered when prescribing medication for a lactating
      woman. MATERIAL AND METHOD: The article is a review based on a discretionary
      selection of articles found after a search in PubMed, recommendations from
      Norwegian and international expert groups, and the authors' own studies and
      experience. RESULTS: Recommendations concerning the use of drugs among breast
      feeding women tend to be based on studies in which the degree of drug transfer to
      the mother's milk has been measured or on case studies, sometimes in combination
      with pharmacokinetic or pharmacodynamic considerations. The toxicity and dosage
      of the medication, duration of treatment, as well as the infant's age and health
      condition need to be considered. Psychotropic drugs are the drug group for which
      most studies have been published. This is also the group for which individual
      risk/benefit evaluations are most often required, since a risk of pharmacological
      effects on the infant cannot be excluded. INTERPRETATION: Most drugs can be used
      by breast-feeding women, since the amount transferred to the breast milk is too
      small to have any pharmacological effects on the infant. In most cases, the sum
      of available information in combination with clinical experience will be
      sufficient to provide specific advice about the use of medication during breast
      feeding.

PMID- 22614308
TI  - [Prophylactic medicines for migraine].
AB  - Migraine patients with frequent and disabling attacks should  be given the
      opportunity to test prophylactic medicines, and general practitioners  should
      know the indications and the main principles of treatment.  When testing a
      preventative drug, it is important that the patient  has realistic expectations,
      keeps a headache diary, increases the  doses gradually, and takes an adequate
      dose for at least two months  before the effect is assessed. Drugs licensed in
      Norway with adequate  scientific documentation for use as migraine prophylactics
      include  some antihypertensives (beta-blockers, candesartan and lisinopril), 
      antiepileptics (topiramate, valproate and gabapentin), an antidepressant
      (amitriptyline),  and botulinum toxin for chronic migraine. In the choice of
      medicine, one  should consider scientific evidence, side effects and
      contraindications,  effect on comorbid conditions, simplicity of use, and price.
      Patients  who are severely affected should try at least three different drugs  in
      succession.

PMID- 22614309
TI  - [Cardiac arrest in a 10-month-old boy with  spinal cord injury].
AB  - A 10-month-old boy with a previous upper spinal cord injury was  admitted to
      hospital with acute respiratory and circulatory distress.  Shortly after
      admission the boy had severe bradycardia leading to  asystolia and pulseless
      electrical activity. He was successfully  resuscitated, and the investigation
      that followed excluded infection,  congenital heart defect, arrhythmia and
      cerebral haemorrhage. Over  the following days the patient had several episodes
      of isolated  bradycardia and combined bradycardia and hypotension. It was
      concluded  that the patient suffered from autonomic dysreflexia, triggered  by a
      distended urinary bladder. He was treated with intermittent  catheterization and
      a permanent pacemaker, and after 12 months there  have not been any symptomatic
      episodes or registered arrhythmias. Autonomic dysreflexia is a common and well
      known complication  of spinal cord injury above Th6, but the literature on
      paediatric patients  is scarce. Our case report presents an infant with an
      atypical and  severe episode of autonomic dysreflexia. Patients with spinal cord 
      injury, their caregivers and health-care personal should be aware  of this
      complication of spinal cord injury, in order to prevent and  treat autonomic
      dysreflexia properly and avoid potentially fatal  episodes.

PMID- 22614310
TI  - [Bradyarrhythmias early after spinal cord injury].

PMID- 22614311
TI  - An elderly man with atrial  fibrillation and exacerbated diabetes.

PMID- 22614312
TI  - Digitalis and diabetes.

PMID- 22614313
TI  - [Spinal cord injury and bowel function].
AB  - BACKGROUND: Spinal cord injury (SCI) often causes permanent disruptions of
      gastrointestinal function, which exacerbates functional disablement. MATERIAL AND
      METHOD: The article is based on the authors' own clinical experience at tertiary
      level in the specialist health service and literature searches in PubMed.
      RESULTS: Neurogenic gastrointestinal dysfunction is a common sequela of injury to
      the spinal cord. Obstipation and faecal incontinence entail treatment that is
      often time- and resource-consuming. It is not yet possible to treat the cause of
      the condition. New treatment methods with retrograde and antegrade irrigation of
      the rectocolon, transanally or by means of appendicostomy, result in a greater
      degree of self-sufficiency and faster evacuation procedures. INTERPRETATION:
      Neurogenic gastrointestinal dysfunction following a spinal cord injury should be
      assessed and treated in a tertiary level rehabilitation department. The function
      loss is permanent, and the treatment must be systematically tested and regularly
      evaluated. The decision as to which treatment is appropriate has to be taken by
      the patient and the healthcare system. Individual and personal factors must be
      taken into account. The newly established international consensus, with
      standardised data sets for evaluating function loss due to spinal cord injuries,
      paves the way for new and greater possibilities for multi-centre cooperation on
      quality assurance and research.

PMID- 22614314
TI  - Respiratory complications associated with spinal cord injury.
AB  - BACKGROUND: Respiratory complications are the most common cause of acute and long
      term morbidity and mortality in patients with spinal cord injury. MATERIAL AND
      METHODS: The article is based on a non-systematic search in PubMed and the
      authors' clinical experience in treatment and follow-up of respiratory
      complications in patients with spinal cord injury. RESULTS: The extent of
      respiratory complications is dependent on the level of spinal cord injury and the
      degree of motor completeness. In acute spinal cord injury, 80 % of patients may
      suffer from respiratory complications. Long-term follow-up indicates that
      respiratory complications are the most common cause of death in these patients.
      The most common respiratory complications are atelectasis, pneumonia and
      respiratory failure. Prevention of respiratory complications must be initiated
      immediately, independent of the level of spinal cord injury. The question of
      mechanical ventilation in the acute setting, and also during long-term follow-up
      must be addressed, along with aggressive secretion management. Patients with
      spinal cord injury have a high prevalence of sleep apnea that may influence their
      quality of life and rehabilitation. INTERPRETATION: Respiratory complications are
      common in patients with spinal cord injury. These patients need a
      multidisciplinary approach. All disciplines involved must obtain knowledge of
      respiratory complications in the acute phase and in the longer term, to ensure
      patients are referred for necessary pulmonary review and follow-up.

PMID- 22614315
TI  - Cardiovascular complications of spinal cord injury.
AB  - BACKGROUND: The aim of this paper is to provide an overview of the autonomic
      innervation of the cardiovascular system and the cardiovascular sequelae of
      spinal cord injuries. METHOD: A literature search was carried out in the PubMed
      database, with the search phrases "traumatic spinal cord injury"/"traumatic
      spinal cord injuries" together with "autonomic dysfunction", "autonomic
      dysreflexia" and "cardiovascular disease". RESULTS: The most important
      cardiovascular complications in the acute phase are bradyarrhythmia, hypotension,
      enhanced vasovagal reflexes, supraventricular/ventricular ectopic beats,
      vasodilation and venous stasis. Important in the chronic phase are orthostatic
      hypotension and impaired regulation of blood pressure, blood volume and body
      temperature. Tetraplegia is frequently accompanied by autonomic dysreflexia,
      impaired transmission of cardial pain, loss of muscle mass in the left ventricle
      and pseudoinfarction. Patients with injuries above the sixth thoracic vertebra
      have a predisposition for autonomic dysreflexia. This is a condition
      characterised by sudden, uncontrolled sympathetic response accompanied by a rise
      in blood pressure. Autonomic dysreflexia usually leads to headaches and erythema
      on the upper chest. The condition may cause cerebral haemorrhage and is
      potentially life threatening. Patients with spinal cord injuries have an
      increased risk of atherosclerotic disease due to overweight, lipid disorders,
      metabolic syndrome and diabetes. They are predisposed to thrombotic emboli due to
      venous stasis and hypercoagulopathy, particularly immediately after the injury.
      INTERPRETATION: Knowledge of cardiovascular sequelae after spinal cord injuries
      and assessment of these is important for correct diagnostics, planning of
      preventive measures and optimal treatment.

PMID- 22614316
TI  - [The knowledgeable patients].

PMID- 22614317
TI  - [Steer clear of buzzwords].

PMID- 22614321
TI  - Clinical spectrum of tuberculous optic neuropathy.
AB  - PURPOSE: Tuberculous optic neuropathy may follow infection with Mycobacterium
      tuberculosis or administration of the bacille Calmette-Guerin. However, this
      condition is not well described in the ophthalmic literature. METHODS:
      Ophthalmologists, identified through professional electronic networks or previous
      publications, collected standardized clinical data relating to 62 eyes of 49
      patients who they had managed with tuberculous optic neuropathy. RESULTS:
      Tuberculous optic neuropathy was most commonly manifested as papillitis (51.6 %),
      neuroretinitis (14.5 %), and optic nerve tubercle (11.3 %). Uveitis was an
      additional ocular morbidity in 88.7 % of eyes. In 36.7 % of patients, extraocular
      tuberculosis was present. The majority of patients (69.4 %) had resided in and/or
      traveled to an endemic area. Although initial visual acuity was 20/50 or worse in
      62.9 % of 62 eyes, 76.7 % of 60 eyes followed for a median of 12 months achieved
      visual acuities of 20/40 or better. Visual field defects were reported for 46.8 %
      of eyes, but these defects recovered in 63.2 % of 19 eyes with follow-up.
      CONCLUSION: Visual recovery from tuberculous optic neuropathy is common, if the
      diagnosis is recognized and appropriate treatment is instituted. A tuberculous
      etiology should be considered when evaluating optic neuropathy in persons from
      endemic areas.

PMID- 22614322
TI  - CC chemokine ligand 7 expression in liver metastasis of colorectal cancer.
AB  - The main cause of death for colorectal cancer (CRC) patients is the development
      of metastatic lesions at sites distant from the primary tumor. Therefore, it is
      important to find biomarkers that are related to the metastasis and to study the
      possible mechanisms. Recent data have shown that soluble attractant molecules
      called chemokines support the metastasis of certain cancers to certain organs. To
      identify molecular regulators that are differentially expressed in liver
      metastasis of CRC, PCR array analysis was performed and CC chemokine ligand 7
      (CCL7) showed remarkable overexpression in liver metastatic tumor tissues. To
      validate the results of the PCR array, 30 patients with primary CRC and liver
      metastases were selected. Immunohistochemistry and real-time PCR analysis showed
      that CCL7 was expressed in normal colonic epithelium and the expression was
      higher in liver metastases compared to primary CRC (p<0.001). Real-time PCR
      showed that the expression of CCR1, CCR2 and CCR3 was also higher in liver
      metastases compared to primary CRC (p=0.001, p=0.033 and p<0.001, respectively).
      In conclusion, correlation of CCL7 overexpression and its receptor expression
      with colon cancer liver metastasis suggests that CCL7 as a novel target in liver
      metastasis of CRC may be of potential clinical value for the prevention of
      hepatic recurrences.

PMID- 22614323
TI  - The use of simulation in healthcare:  from systems issues, to team building, to
      task training, to education and high stakes examinations.
AB  - PURPOSE OF REVIEW: Simulation in healthcare is becoming increasingly used. This
      review will spotlight some of the uses of simulation in healthcare training.
      RECENT FINDINGS: Previously, evaluation of simulation training was typically from
      evaluations from trainees. Recent articles, however, have linked simulation
      training to actual patient outcomes and demonstrated skill retention up to 1
      year. Objective measurements have demonstrated positive effects on healthcare
      education, have been successfully used in high stakes examinations, and have
      uncovered systems and patient safety issues. SUMMARY: This article will review
      some recent studies showing how simulation can have a positive effect on patient
      outcomes and skill retention, uncover systems issues related to patient safety,
      and how simulation can be used in credentialing, and other high stakes
      examinations.

PMID- 22614324
TI  - Risk stratification and treatment strategy of pulmonary embolism.
AB  - PURPOSE OF REVIEW: Pulmonary embolism remains one of the leading causes of
      cardiovascular mortality. The wide range of reported mortality rates reflects
      heterogeneity in comorbidity and severity of pulmonary embolism. Optimizing risk
      stratification to prognose pulmonary embolism patients appears to be important to
      improve management, treatment and clinical outcome. RECENT FINDINGS: Hemodynamic
      status is the most important short-term prognostic factor. High-risk pulmonary
      embolism or massive pulmonary embolism is defined by the patient response more
      than the clot size: patients with circulatory shock including sustained
      hypotension should receive thrombolytic therapy in absence of contraindications.
      Nonmassive or normotensive pulmonary embolism can be further stratified using
      clinical features, imaging (echocardiography, computed tomography) and biomarkers
      (troponins, natriuretic peptides): low-risk pulmonary embolism, evaluated by
      clinical model (Pulmonary Embolism Severity Index; PESI) can potentially be
      treated as outpatients; and intermediate-risk pulmonary embolism, which can be
      further stratified into less-severe and more-severe intermediate risk. The last
      may benefit from intensive clinical surveillance but the risk-benefit ratio for
      thrombolysis has been inadequately quantified to make any strong recommendation.
      New anticoagulants may transform traditional pulmonary embolism treatment.
      SUMMARY: Optimizing risk stratification of patients with normotensive pulmonary
      embolism before they develop overt hemodynamic instability is the challenge of
      current pulmonary embolism management. Treatment strategy has to integrate this
      risk stratification and new anticoagulants arrival.

PMID- 22614325
TI  - ALKoma: a cancer subtype with a shared target.
AB  - Anaplastic lymphoma kinase (ALK) is a receptor-type protein tyrosine kinase that
      is currently the focus of much attention in oncology. ALK is rendered oncogenic
      as a result of its fusion to NPM1 in anaplastic large cell lymphoma, to TPM3 or
      TPM4 in inflammatory myofibroblastic tumor, to EML4 in non-small cell lung
      carcinoma, and to VCL in renal medullary carcinoma. It is also activated as a
      result of missense mutations in neuroblastoma and anaplastic thyroid cancer.
      Whereas these various tumors arise in different organs, they share activated ALK,
      and a marked clinical efficacy with ALK inhibitors has already been shown for
      some of the tumors with ALK fusions. One of such compound, crizotinib, is now
      approved in the United States for the treatment of lung cancer positive for ALK
      rearrangement. I propose that tumors carrying abnormal ALK as an essential growth
      driver be collectively termed "ALKoma."

PMID- 22614328
TI  - Synthesis of AgInS2 nanocrystal ink and its photoelectrical application.
AB  - This paper reports a hot-injection method of preparing AgInS2 nanocrystals with
      different sizes and morphologies, starting with the capping agents of oleylamine
      and dodecylthiol, and varying the reaction conditions. The effects of the
      temperature and time on the growth of AgInS2 nanocrystals are investigated. These
      parameters have a tremendous impact on the size and morphology of the
      nanocrystals, allowing the controlled synthesis of shapes including nanoparticles
      and nanorods. It has been found that the size of the nanoparticles and nanorods
      can be controlled by changing the time of nanocrystal growth. The evolution from
      nanoparticles to nanorods can be controlled by the reaction temperature. The
      possible formation mechanism and growth process of the AgInS2 nanocrystals are
      discussed based on the experimental results. The AgInS2 nanocrystal ink with a
      bandgap of 1.90 eV can produce crack-free films. As a proof-of-concept, thin film
      solar cells made by using such AgInS2 films as absorber layers are tested for
      their viability as a type of solar cell material and are found to exhibit a
      measurable photovoltaic response. 

PMID- 22614329
TI  - Quartic Box-Spline Reconstruction on the BCC Lattice.
AB  - This paper presents an alternative box-spline filter for the body-centered cubic
      (BCC) lattice, the seven-direction quartic box-spline M7 that has the same
      approximation order as the eight-direction quintic box-spline M8 but a lower
      polynomial degree, smaller support, and is computationally more efficient. When
      applied to reconstruction with quasi-interpolation prefilters, M7 shows less
      aliasing, which is verified quantitatively by integral filter metrics and
      frequency error kernels. To visualize and analyze distributional aliasing
      characteristics, each spectrum is evaluated on the planes and lines with various
      orientations. 

PMID- 22614330
TI  - Semiregular solid texturing from 2D image exemplars.
AB  - Solid textures, comprising 3D particles embedded in a matrix in a regular or
      semiregular pattern, are common in natural and man-made materials, such as
      brickwork, stone walls, plant cells in a leaf, etc. We present a novel technique
      for synthesizing such textures, starting from 2D image exemplars which provide
      cross-sections of the desired volume texture. The shapes and colors of typical
      particles embedded in the structure are estimated from their 2D cross-sections.
      Particle positions in the texture images are also used to guide spatial placement
      of the 3D particles during synthesis of the 3D texture. Our experiments
      demonstrate that our algorithm can produce higher quality structures than
      previous approaches; they are both compatible with the input images, and have a
      plausible 3D nature.

PMID- 22614331
TI  - A time-dependent vector field topology based on streak surfaces.
AB  - It was shown recently how the 2D vector field topology concept, directly
      applicable to stationary vector fields only, can be generalized to time-dependent
      vector fields by replacing the role of stream lines by streak lines. The present
      paper extends this concept to 3D vector fields. In traditional 3D vector field
      topology separatrices can be obtained by integrating stream lines from 0D seeds
      corresponding to critical points. We show that in our new concept, in contrast,
      1D seeding constructs are required for computing streak-based separatrices. In
      analogy to the 2D generalization we show that invariant manifolds can be obtained
      by seeding streak surfaces along distinguished path surfaces emanating from
      intersection curves between codimension-1 ridges in the forward and reverse
      finite-time Lyapunov exponent (FTLE) fields. These path surfaces represent a time
      dependent generalization of critical points and convey further structure in time
      dependent topology of vector fields. Compared to the traditional approach based
      on FTLE ridges, the resulting streak manifolds ease the analysis of Lagrangian
      coherent structures (LCS) with respect to visual quality and computational cost,
      especially when time series of LCS are computed. We exemplify validity and
      utility of the new approach using both synthetic examples and computational fluid
      dynamics results.

PMID- 22614332
TI  - Quantitative modeling of transcriptional regulatory networks by integrating
      multiple source of knowledge.
AB  - A key challenge in the post genome era is to identify genome-wide transcriptional
      regulatory networks, which specify the interactions between transcription factors
      and their target genes. In this work, a regulatory model-based binding energy is
      proposed to quantify the transcriptional regulatory network. Multiple quantities,
      including binding affinity, regulatory efficiency, and the activity level of
      transcription factor (TF) are incorporated into a general learning model. The
      sequence features of the promoter are exploited to derive the binding energy.
      Comparing with the previous models that only employ microarray data, the proposed
      model can bridge the gap between the relative background frequency of the
      observed nucleotide and the gene's transcription rate. Experimental results show
      that the proposed model can effectively identify the parameters and the activity
      level of TF. Moreover, the kinetic parameters introduced in the proposed model
      can reveal more biological sense than some previous models can do.

PMID- 22614333
TI  - Reaction rate reconstruction from biomass concentration measurement in
      bioreactors using modified second-order sliding mode algorithms.
AB  - This paper deals with the estimation of unknown signals in bioreactors using
      sliding observers. Particular attention is drawn to estimate the specific growth
      rate of microorganisms from measurement of biomass concentration. In a recent
      article, notions of high-order sliding modes have been used to derive a growth
      rate observer for batch processes. In this paper we generalize and refine these
      preliminary results. We develop a new observer with a different error structure
      to cope with other types of processes. Furthermore, we show that these observers
      are equivalent, under coordinate transformations and time scaling, to the
      classical super-twisting differentiator algorithm, thus inheriting all its
      distinctive features. The new observers' family achieves convergence to time
      varying unknown signals in finite time, and presents the best attainable
      estimation error order in the presence of noise. In addition, the observers are
      robust to modeling and parameter uncertainties since they are based on minimal
      assumptions on bioprocess dynamics. In addition, they have interesting
      applications in fault detection and monitoring. The observers performance in
      batch, fed-batch and continuous bioreactors is assessed by experimental data
      obtained from the fermentation of Saccharomyces Cerevisiae on glucose.

PMID- 22614326
TI  - The Alzheimer's Disease Assessment Scale-Cognitive-Plus (ADAS-Cog-Plus): an
      expansion of the ADAS-Cog to improve responsiveness in MCI.
AB  - BACKGROUND: The Alzheimer's Disease Assessment Scale cognitive subscale (ADAS
      Cog) is widely used in AD, but may be less responsive to change when used in
      people with mild cognitive impairment (MCI). METHODS: Participants from the
      Alzheimer's Disease Neuroimaging Initiative were administered a
      neuropsychological battery and 1.5 T MRI scans over 2-3 years. Informants were
      queried regarding functional impairments. Some participants had lumbar punctures
      to obtain cerebrospinal fluid (CSF). We added executive functioning (EF) and
      functional ability (FA) items to the ADAS-Cog to generate candidate augmented
      measures. We calibrated these candidates using baseline data (n = 811) and
      selected the best candidate that added EF items alone and that added EF and FA
      items. We selected candidates based on their responsiveness over three years in a
      training sample of participants with MCI (n = 160). We compared traditional ADAS
      Cog scores with the two candidates based on their responsiveness in a validation
      sample of participants with MCI (n = 234), ability to predict conversion to
      dementia (n = 394), strength of association with baseline MRI (n = 394) and CSF
      biomarkers (n = 193). RESULTS: The selected EF candidate added category fluency
      (ADAS Plus EF), and the selected EF and FA candidate added category fluency,
      Digit Symbol, Trail Making, and five items from the Functional Assessment
      Questionnaire (ADAS Plus EF&FA). The ADAS Plus EF& FA performed as well as or
      better than traditional ADAS-Cog scores. CONCLUSION: Adding EF and FA items to
      the ADAS-Cog may improve responsiveness among people with MCI without impairing
      validity.

PMID- 22614327
TI  - CSF biomarker associations with change in hippocampal volume and precuneus
      thickness: implications for the Alzheimer's pathological cascade.
AB  - Neurofibrillary tangles (NFT) and amyloid plaques are hallmark neuropathological
      features of Alzheimer's disease (AD). There is some debate as to which
      neuropathological feature comes first in the disease process, with early autopsy
      studies suggesting that NFT develop first, and more recent neuroimaging studies
      supporting the early role of amyloid beta (Abeta) deposition. Cerebrospinal fluid
      (CSF) biomarkers of Abeta42 and hyperphosphorylated tau (p-tau) have been shown
      to serve as in vivo proxy measures of amyloid plaques and NFT, respectively. The
      aim of this study was to examine the association between CSF biomarkers and rate
      of atrophy in the precuneus and hippocampus. These regions were selected because
      the precuneus appears to be affected early and severely by Abeta deposition, and
      the hippocampus similarly by NFT pathology. We predicted (1) baseline Abeta42
      would be related to accelerated rate of cortical thinning in the precuneus and
      volume loss in the hippocampus, with the latter relationship expected to be
      weaker, (2) baseline p-tau(181p) would be related to accelerated rate of
      hippocampal atrophy and cortical thinning in the precuneus, with the latter
      relationship expected to be weaker. Using all ADNI cohorts, we fitted separate
      linear mixed-effects models for changes in hippocampus and precuneus longitudinal
      outcome measures with baseline CSF biomarkers modeled as predictors. Results
      partially supported our hypotheses: Both baseline p-tau(181p) and Abeta42 were
      associated with hippocampal atrophy over time. Neither p-tau(181p) nor Abeta42
      were significantly related to cortical thinning in the precuneus over time.
      However, follow-up analyses demonstrated that having abnormal levels of both
      Abeta42 and p-tau(181p) was associated with an accelerated rate of atrophy in
      both the hippocampus and precuneus. Results support early effects of Abeta in the
      Alzheimer's disease process, which are less apparent than and perhaps dependent
      on p-tau effects as the disease progresses. However, amyloid deposition alone may
      be insufficient for emergence of significant morphometric changes and clinical
      symptoms.

PMID- 22614335
TI  - The role of human peritoneal mesothelial cells in the fibrosis and progression of
      gastric cancer.
AB  - Peritoneal dissemination is the most frequent metastatic pattern of scirrhous
      gastric cancer. However, despite extensive research effort, disease outcomes have
      not improved sufficiently. Tumor progression and metastasis result from
      interactions between cancer and various cells in the stroma, including
      endothelial cells, immune cells and fibroblasts. Fibroblasts have been
      particularly well studied; they are known to change into carcinoma-associated
      fibroblasts (CAFs) and produce transforming growth factor beta (TGF-beta), which
      mediates cancer-stroma interactions. Here, we investigated whether TGF-beta
      derived from cancer cells in the peritoneal microenvironment activates human
      peritoneal mesothelial cells (HPMCs), leading to the progression and fibrosis of
      gastric cancer. We found that activated HPMCs (a-HPMCs) took on a spindle shape
      formation, decreased the expression of E-cadherin and increased that of alpha
      SMA. Furthermore, a-HPMCs became more invasive and upregulated proliferation of
      human gastric cancer-derived MKN45 cells following direct cell-cell contact.
      Notably, MKN45 cells co-cultured with a-HPMCs also acquired anchorage-independent
      cell growth and decreased expression of E-cadherin in vitro. To measure the
      effects of the co-culture in vivo, we developed a mouse xenograft model into
      which different culture products were subcutaneously injected. The largest tumors
      were observed in mice that had been given MKN45 cells co-cultured with a-HPMCs.
      Furthermore, these tumors contained HPMC-derived fibrous tissue. Thus, the
      epithelial-mesenchymal transition (EMT) of HPMCs appears to drive peritoneal
      dissemination and tumor fibrosis.

PMID- 22614334
TI  - Proteomics reveals drastic increase of extracellular matrix proteins collagen and
      dermatopontin in the aged mdx diaphragm model of Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy is a lethal genetic disease of childhood caused by
      primary abnormalities in the gene coding for the membrane cytoskeletal protein
      dystrophin. The mdx mouse is an established animal model of various aspects of X
      linked muscular dystrophy and is widely used for studying fundamental mechanisms
      of dystrophinopathy and testing novel therapeutic approaches to treat one of the
      most frequent gender-specific diseases in humans. In order to determine global
      changes in the muscle proteome with the progressive deterioration of mdx tissue
      with age, we have characterized diaphragm muscle from mdx mice at three ages (8
      weeks, 12-months and 22-months) using mass spectrometry-based proteomics. Altered
      expression levels in diaphragm of 8-week vs. 22-month mice were shown to occur in
      11 muscle-associated proteins. Aging in the mdx diaphragm seems to be associated
      with a drastic increase in the extracellular matrix proteins, collagen and
      dermatopontin, the molecular chaperone alphaB-crystallin, and the intermediate
      filament protein vimentin, suggesting increased accumulation of connective
      tissue, an enhanced cellular stress response and compensatory stabilization of
      the weakened membrane cytoskeleton. These proteomic findings establish the aged
      mdx diaphragm as an excellent model system for studying secondary effects of
      dystrophin deficiency in skeletal muscle tissue.

PMID- 22614336
TI  - Implementation of a standards-based anaesthesia record compliant with the health
      level 7 (HL7) clinical document architecture (CDA).
AB  - With the increasing use of anaesthesia information management systems (AIMS)
      there is the opportunity for different institutions to aggregate and share
      information both nationally and internationally. Potential uses of such
      aggregated data include outcomes research, benchmarking and improvement in
      clinical practice and patient safety. However, these goals can only be achieved
      if data contained in records from different sources are truly comparable and
      there is semantic inter-operability. This paper describes the development of a
      standard terminology for anaesthesia and also a Domain Analysis Model and
      implementation guide to facilitate a standard representation of AIMS records as
      extensible markup language documents that are compliant with the Health Level 7
      Version 3 clinical document architecture. A representation of vital signs that is
      compliant with the International Standards Organization 11073 standard is also
      discussed.

PMID- 22614337
TI  - Airway management practices in adult intensive care units in Israel: a national
      survey.
AB  - Timely and adequate management of normal and compromised airway is a crucial task
      facing medical teams taking care of patients in intensive care units. We
      investigated the airway management practices in the Israeli intensive care units
      (ICUs). A postal survey was sent to the 20 main ICUs in Israel. We investigated
      which medical specialty (ICU, anesthesiology or ENT) is involved with airway
      management in the ICUs and summarized the availability of airway equipment and
      medication necessary for endotracheal intubation, the use of dedicated airway
      management algorithms, the approaches to specific airway scenarios and education
      in airway management. The response rate was 70 % (14 out of the 20 units).
      Intubation with normal airway is performed mainly by ICU doctors (86 %). A
      difficult airway is most frequently cared for by anesthesiologists (79 %), while
      impossible intubation/mask ventilation is mainly managed by anesthesiologists and
      ENT surgeons (50-79 %). Airways in C-spine injury are mainly managed by
      anesthesiologists (70 %). Surgical airway is mainly performed by ENT surgeons (79
      %). The ASA difficult airway algorithm is used in 71 % of the units. Fiberoptic
      intubation is used significantly more often than other methods in two scenarios:
      78 % of the difficult airways and 64 % of the C-spine injuries (p < 0.0001). Only
      43 % of the units reported holding quality assurance meetings. 69 % of the units'
      heads are satisfied with their airway management policies. Equipment and
      medications necessary for airway management are available in most of the units.
      Difficult airways in ICUs are mainly managed by anesthesiologists and ENT
      surgeons. Few ICUs have quality assurance meetings.

PMID- 22614338
TI  - Effects of Porphyromonas gingivalis surface-associated material on osteoclast
      formation.
AB  - Porphyromonas gingivalis strongly correlates with periodontitis, but the
      underlying mechanisms causing dentoalveolar bone resorption are not fully
      understood. As contradictory effects of P. gingivalis on osteoclastogenesis have
      been reported, this study investigates the effect of P. gingivalis extract on
      osteoclast formation. Osteoclast formation in mouse bone marrow (MBM) cell
      cultures and RAW 264.7 cells was stimulated by nuclear factor-kappaB ligand
      (RANKL) or parathyroid hormone (PTH). Cells were cultured with and without P.
      gingivalis surface-associated material and phenotypic characteristics were
      examined using microscopy, flow cytometry, and RT-PCR. P. gingivalis
      significantly decreased osteoclast formation and the expression of osteoclast
      phenotypic markers in PTH-stimulated MBM cultures. Additionally, P. gingivalis
      inhibited expression of osteoclast differentiation factors and stimulated
      expression of the mouse macrophage marker F4/80. The presence of P. gingivalis in
      RANKL-stimulated MBM cultures and RAW 264.7 cells inhibited osteoclastogenesis.
      Interestingly, a transient exposure with P. gingivalis before PTH stimulation
      increased osteoclastogenesis in MBM cultures. Flow cytometric analyses of cells
      transiently exposed to P. gingivalis demonstrated an increased proportion of
      potential osteoclast precursor cells. We conclude that a transient exposure of
      MBM cultures to P. gingivalis increases the number of osteoclast precursors and
      osteoclast formation, whereas a prolonged exposure completely abolishes
      osteoclastogenesis. 

PMID- 22614340
TI  - Biodefluorination and biotransformation of fluorotelomer alcohols by two alkane
      degrading Pseudomonas strains.
AB  - Fluorotelomer alcohols [FTOHs, F(CF(2))(n) CH(2)CH(2)OH, n = 4, 6, and 8] are
      emerging environmental contaminants. Biotransformation of FTOHs by mixed
      bacterial cultures has been reported; however, little is known about the
      microorganisms responsible for the biotransformation. Here we reported
      biotransformation of FTOHs by two well-studied Pseudomonas strains: Pseudomonas
      butanovora (butane oxidizer) and Pseudomonas oleovorans (octane oxidizer). Both
      strains could defluorinate 4:2, 6:2, and 8:2 FTOHs, with a higher degree of
      defluorination for 4:2 FTOH. According to the identified metabolites, P.
      oleovorans transformed FTOHs via two pathways I and II. The pathway I led to the
      production of x:2 ketone [dominant metabolite, F(CF(2))(x)C(O)CH(3); x = n - 1, n
      = 6 or 8], x:2 sFTOH [F(CF(2))(x)CH(OH)CH(3)], and perfluorinated carboxylic
      acids (PFCAs, perfluorohexanoic, or perfluorooctanoic acid). The pathway II
      resulted in the formation of x:3 polyfluorinated acid [F(CF(2))(x) C(2)CH(2)
      COOH] and relatively minor shorter-chain PFCAs (perfluorobutyric or
      perfluorohexanoic acid). Conversely, P. butanovora transformed FTOHs by using the
      pathway I, leading to the production of x:2 ketone, x:2 sFTOH, and PFCAs. This is
      the first study to show that individual bacterium can bio-transform FTOHs via
      different or preferred transformation pathways to remove multiple --CF(2) --
      groups from FTOHs to form shorter-chain PFCAs.

PMID- 22614339
TI  - Regulation of pancreatic beta-cell survival by nitric oxide: clinical relevance.
AB  - The reduction of pancreatic beta-cell mass is an important factor in the
      development of type 1 and type 2 diabetes. Understanding the mechanisms that
      regulate the maintenance of pancreatic beta-cell mass as well as beta-cell death
      is necessary for the establishment of therapeutic strategies. In this context,
      nitric oxide (NO) is a diatomic, gaseous, highly reactive molecule with
      biological activity that participates in the regulation of pancreatic beta-cell
      mass. Two types of cellular responses can be distinguished depending on the level
      of NO production. First, pancreatic beta-cells exposed to inflammatory cytokines,
      lipid stress or hyperglycaemia produce high concentrations of NO, mainly due to
      the activation of inducible NO synthase (iNOS), thus promoting cell death.
      Meanwhile, under homeostatic conditions, low concentrations of NO, constitutively
      produced by endothelial NO synthase (eNOS), promote cell survival. Here, we will
      discuss the current knowledge of the NO-dependent mechanisms activated during
      cellular responses, emphasizing those related to the regulation of cell survival.

PMID- 22614341
TI  - Vinyl-triphenylamine dyes, a new family of switchable fluorescent probes for
      targeted two-photon cellular imaging: from DNA to protein labeling.
AB  - On the basis of our previous work on vinyl-triphenylamine derived DNA
      fluorophores we explored the structure space around this core by coupling it to
      diverse cationic, anionic and zwitterionic groups in the aim of targeting
      different classes of biomolecules. In parallel core modifications were performed
      to optimize the photophysical properties (quantum yield, two-photon absorption).
      The resulting water soluble pi-conjugated molecules are called TP dyes and
      display an exceptional combination of optical properties: high two-photon
      absorption cross-section, high photostability, no self-quenching, and switchable
      fluorescence emission when bound to a biopolymer matrix. The linear and nonlinear
      optical properties of the TP dyes were studied in vitro in presence of DNA and in
      presence of a model protein (human serum albumin) using complementary absorption
      and fluorescence spectroscopy characterization tools. Structure modifications
      enabled to switch from DNA probes (cationic TP-pyridinium series) to protein
      probes (anionic TP-rhodanine series) without affecting the optical properties.
      Finally most TP compounds appear cell-permeant and show an intracellular
      localization consistent with their in vitro target specificity.

PMID- 22614342
TI  - An improved strategy based on  RAPD markers efficiently identified 95 peach
      cultivars.
AB  - DNA  markers have useful applications in cultivar identification. A novel
      analysis  approach called cultivar identification diagram (CID) was developed
      using DNA  markers in the separation of plant individuals. This new strategy is
      less  time- and cost-consuming, has reliable results, and was constructed for 
      fingerprinting. Ten 11-mer primers were used to amplify the genotypes; all 95 
      peach genotypes (from the National Peach Germplasm Repository, in Nanjing, 
      China) were distinguished by a combination of 54 primers. The utilization of  the
      CID among these 95 peach cultivars was also verified by the identification  of
      three randomly chosen groups of cultivars. This identification showed some 
      advantages including the use of fewer primers and easy separation of all 
      cultivars by the corresponding primers marked in the right position on the CID. 
      This peach CID could provide the information to separate any peach cultivars of 
      these 95, which may be of help to the peach industry in China and for the 
      utilization of DNA markers to identify other plant species.

PMID- 22614343
TI  - Variation of genomic DNA  methylation in the nitrate reductase gene of sibling
      tobacco (Nicotiana  tabacum) cultivars.
AB  - To  better understand genomic DNA methylation in sibling plant cultivars, 
      methylation-sensitive amplification polymorphism analysis was used to 
      investigate two sibling tobacco cultivars, Yunyan85 and Yunyan87, and their two 
      parents, K326 and Yunyan No. 2. Differences in the degree of genomic DNA 
      methylation were found among the four tobacco cultivars. Compared with parents, 
      the two sibling cultivars had fewer methylated sites. Twenty-nine  methylation
      sensitive amplification polymorphism fragments that exhibited  methylation
      alteration in the four tobacco cultivars were recovered and  sequenced. BLAST
      (nucleotide BLAST) searches showed that two of the 29  sequences have 99%
      similarity with nucleotides 1442-1694 of the nia-1 gene  and the other 27
      sequences contain GC, CAAT or TATA box. The nitrate reductase  genes from
      Yunyan87, K326 and Yunyan No. 2 were found to be identical; however,  the third
      intron of the nitrate reductase gene from Yunyan85 was different  compared to the
      third introns of Yunyan87, K326 and Yunyan No. 2. We conclude  that methylation
      alteration of promoter regions could be responsible for the  different phenotypes
      in tobacco and that introns of the nitrate reductase gene  can vary as a result
      of intra-species crossing in tobacco.

PMID- 22614344
TI  - Lack of association of the G22A polymorphism of the ADA gene  in patients with
      ankylosing  spondylitis.
AB  - Genes located outside the HLA region (6p21) have been  considered as candidates
      for susceptibility to ankylosing spondylitis. We  tested the hypothesis that the
      G22A polymorphism of the adenosine  deaminase gene (ADA; 20q13.11) is associated
      with ankylosing spondylitis  in 166 Brazilian subjects genotyped for the HLA*27
      gene (47 patients and  119 controls matched for gender, age and geographic
      origin). The HLA-B*27 gene  and the G22A ADA polymorphism were identified by PCR
      with  sequence-specific oligonucleotide probes and PCR-RFLP, respectively. There
      were  no significant differences in frequencies of ADA genotypes [odds ratio 
      (OR) = 1.200, 95% confidence interval (CI) = 0.3102-4.643, P > 0.8] and ADA*01
      and ADA*02 alleles (OR = 1.192, 95%CI = 0.3155-4.505, P > 0.8) in  patients
      versus controls. We conclude that the G22A polymorphism is not  associated with
      ankylosing spondylitis.

PMID- 22614346
TI  - Use of simple sequence repeat  markers for DNA fingerprinting and diversity
      analysis  of sugarcane (Saccharum spp) cultivars  resistant and susceptible to
      red rot.
AB  - Red rod  is an economically important disease of sugarcane caused by the fungus
      Colletotrichum  falcatum. We used a simple sequence repeat (SSR)-based marker
      system to  identify and analyze genetic relationships of red rot resistant and
      susceptible  sugarcane cultivars grown in Pakistan. Twenty-one highly polymorphic
      SSR  markers were used for DNA fingerprinting and genetic diversity analysis of
      20  sugarcane cultivars. These SSR markers were found to be highly robust; we 
      identified 144 alleles, with 3-11 alleles per marker and a mean of 6.8. Three 
      SSR markers were able to identify all 20 cultivars. DNAMAN((r))-generated 
      homology tree was used to analyze genetic diversity among these cultivars; all 
      cultivars shared 58% or more similarity. We correlated polymorphism information 
      content and resolving power values with marker effectiveness in the process of 
      sugarcane cultivar identification. We concluded that a small number of  SSR
      derived DNA markers will allow breeders to identify red rot resistant and 
      susceptible cultivars.

PMID- 22614345
TI  - Frequency of alterations in the MEFV gene and  clinical signs in familial
      Mediterranean fever in Central Anatolia, Turkey.
AB  - Familial Mediterranean fever is a recessive  autoinflammatory disease that is
      frequent in Armenians, Jews, Arabs, and Turks.  The MEFV gene is responsible for
      this disease. We looked for MEFV gene  variations (polymorphism and mutations) in
      a population that resides in Central  Anatolia, Turkey. DNA was extracted from
      peripheral blood leukocytes of 802  familial Mediterranean fever patients. The
      DNA sequence data were examined for  approximately 150 different mutations and
      polymorphisms, including single  nucleotide polymorphisms in different exons of
      the MEFV gene. The  male:female ratio of these patients was 1.44:1. Mutations
      were detected in  48.1% of the patients; 7.5% were homozygous, 11.1% were
      compound heterozygous  and 31.5% had only one identifiable mutant allele. No
      mutations were detected  in 51.9% of the patients. The main clinical
      characteristics of the patients  were: abdominal pain in 20.6%, arthritis in
      22.9% and amyloidosis in 4.6%.  Sixty-six percent of patients had a family
      history of familial Mediterranean  fever; 19.4% of the patients were found to
      have parental consanguinity. We  conclude that the genetics of familial
      Mediterranean fever is more complex than  has previously been reported;
      heterozygous patients presenting a severe  phenotype should be further analyzed
      for less common secondary MEFV mutations,  using gene sequencing.

PMID- 22614347
TI  - Polymorphic microsatellite loci for Japanese Spanish  mackerel (Scomberomorus
      niphonius).
AB  - We isolated and characterized 21 polymorphic  microsatellite loci in Japanese
      Spanish mackerel (Scomberomorus niphonius)  using a (GT)(13)-enriched genomic
      library. Forty individuals were  collected from Qingdao, China. We found 3 to 24
      alleles per locus, with a mean  of 8.8. The observed and expected
      heterozygosities ranged from 0.263 to 0.975  and from 0.385 to 0.946, with means
      of 0.655 and 0.685, respectively. Deviation  from Hardy-Weinberg proportions was
      detected at three loci. Two loci showed  evidence for null alleles. These
      microsatellite markers will be useful for  population genetic analysis of
      Japanese Spanish mackerel.

PMID- 22614348
TI  - Four SNPs of insulin-induced  gene 1 associated with growth and carcass traits in
      Qinchuan cattle in China.
AB  - The  insulin-induced gene 1 (Insig-1) is a regulator of lipid metabolism and
      plays  an important role in the sterol-mediated regulation of SREBP, SCAP and HMG
      CoA  reductase. We used PCR-RFLP and DNA sequencing to detect polymorphisms of
      the  Insig-1 gene in 215 individuals of the Qinchuan cattle breed. Four SNPs 
      [4366(A>G), 4534(T>C), 5001(T>C), and 5235(G>A)] were indentified.  The
      association of the genetic viariation with growth and carcass traits (body 
      length, withers height, hip width, slaughter weight, and carcass weight) was 
      analyzed. The individuals with better performance had the GG genotype at locus 
      A4366G, and CC genotypes at locus T4534C and locus T5001C. These could be used 
      for beef cattle breeding improvement in China. Additionally, linkage 
      disequilibrium analysis reflected that all mutations were in low linkage 
      disequilibrium with each other. We concluded that polymorphisms in the Insig-1 
      gene are associated with growth and carcass traits and could be used for  marker
      assisted selection and management in beef cattle breeding programs.

PMID- 22614349
TI  - Genetic diversity and  assessment of 23 microsatellite markers for parentage
      testing of Santa Ines  hair sheep in Brazil.
AB  - Santa  Ines is the most common hair sheep breed in Brazil and probably has the
      highest  genetic diversity among sheep breeds in this country. Successful
      breeding  programs for Brazilian sheep breeds are not common for various reasons,
      including a lack of control of parentage in the flocks. We developed an allele 
      frequency database for 23 STR loci for the Santa Ines breed based on 285 animals 
      sampled from five populations distributed across the central-western and  north
      eastern regions of Brazil. The marker set included seven microsatellites  used in
      the 2011 International Society for Animal Genetics sheep genotyping  comparison
      tests and all eight microsatellites currently approved by the  Brazilian
      Agricultural Ministry laboratory accreditation guidelines for sheep 
      identification. The microsatellites had an average of 10 alleles and a mean 
      expected heterozygosity of 0.745. Combined paternity exclusion probabilities 
      when no parent or one parent was known were >99.99%. A small proportion (5.8%) 
      of the existing genetic variation was found to be among the Santa Ines 
      populations, possibly derived from genetic drift and selection. We found that 
      the marker panel proposed by the Agricultural Ministry, although generally 
      useful, should be enhanced by including more markers for improved exclusionary 
      power in parentage testing. This database provides a useful tool for parentage 
      testing of this major Brazilian breed, contributing to improved management and 
      breeding of existing herds.

PMID- 22614350
TI  - Genetic diversity of Setipinna  taty (Engraulidae) populations from the China Sea
      based on mitochondrial  DNA control region sequences.
AB  - The  genetic diversity of Setipinna taty, which is commercially fished in the 
      China Sea, was studied based on mitochondrial DNA control region sequences. PCR 
      was used to amplify the control region fragment in 100 individuals of S.  taty
      collected from Weihai (WH), Yantai (YT), Zhoushan (ZS), Xiangshan  (XS), and
      Ninghai (NH) in China. A control region fragment of 656 bp was  successfully
      sequenced in these 100 individuals. The A+T content of this S.  taty control
      region was 71.7%; 172 variable sites and 62 haplotypes were  found. Nucleotide
      diversity in the WH, YT, ZS, XS, and NH groups was 0.0228,  0.0247, 0.0441,
      0.0126, and 0.0238, respectively. The haplotype diversity was  0.984, 0.911,
      0.989, 0.926, and 0.979, respectively. Analysis of molecular  variance showed
      that 97.95% of genetic variation was within populations, and  only 2.05% among
      populations. The neighbor-joining phylogenetic tree obtained  based on genetic
      distance showed that no significant genealogical structure  exists throughout
      this range of S. taty. These results indicate no  apparent geographical
      differentiation in the comparison of Yellow Sea and East  China Sea populations
      of S. taty. Within the control region, we  identified an extended termination
      associated sequence domain, a central  conserved sequence block domain and a
      conserved sequence block domain;  insertions of short tandem repeat sequence
      segments were found at the 5' end of  the control region.

PMID- 22614351
TI  - The role of smoking status and collagen IX polymorphisms in the susceptibility to
      cervical spondylotic myelopathy.
AB  - We investigated a possible association of collagen IX  tryptophan (Trp) alleles
      (Trp2 and Trp3) and smoking with cervical spondylotic  myelopathy (CSM) in 172
      Chinese patients and 176 age- and gender-matched  controls. The smoking status
      was evaluated by smoking index (SI). The CSM cases  had a significantly higher
      prevalence of Trp2 alleles (Trp2+) than controls  (19.8 vs 6.2%, P = 0.002), but
      the prevalence of Trp3 alleles (Trp3+)  was similar between the two groups (23.3
      vs 21.6%, P = 0.713). Logistic  regression analyses showed that the subjects with
      Trp2+ had a higher risk for  CSM. We thus analyzed whether smoking status
      influenced the association between  Trp2 alleles and CSM risk. Among Trp2+
      subjects with an SI less than 100, the  smoking status did not influence the
      effect of risk for SCM [odds ratio (OR) =  1.34, 95% confidential interval
      (95%CI) = 0.85-2.18, P > 0.05]. When SI  increased from 101 to 300, the OR for
      CSM reached 3.34 (95%CI = 2.11-5.67, P =  0.011); when SI was more than 300, the
      OR for CSM reached 5.56 (95%CI =  3.62-7.36, P < 0.001). Among Trp2- subjects
      with SI more than 300, the OR  for CSM increased 2.14 (95%CI = 1.15-4.07, P =
      0.024). We found a significant  association between the Trp2 alleles and CSM risk
      and smoking amplifies this  risk, suggesting that smoking abstinence is important
      for reducing CSM  occurrence in subjects with high genetic risk.

PMID- 22614352
TI  - SRAP analysis of genetic diversity of nine  native populations of wild sugarcane,
      Saccharum spontaneum, from Sichuan, China.
AB  - Saccharum spontaneum is a wild sugarcane species that is native to and  widely
      distributed in China. It has been extensively used in sugarcane breeding 
      programs, and is being tested for the development of bioenergy cultivars. In 
      order to provide basic information for the exploitation of this species, we 
      analyzed genetic variation among and within native S. spontaneum populations 
      collected from Sichuan, China. Eighty plants from nine native populations were 
      sampled. Twenty-one sequence-related amplified polymorphism primer pairs 
      generated 235 clearly scorable bands, of which 185 were polymorphic (78.7%). 
      Nei's genetic diversity was 0.2801 and Shannon's information index was 0.4155 
      across the populations. Genetic diversity parameters, G(ST) value (0.2088) and
      N(m) value (1.8944), showed that the genetic variation  within populations was
      greater than that among populations. In the cluster  analysis, one major grouping
      was formed by populations from Ya'an and another  one by populations from Sichuan
      basin; a population from Baoxing formed a  single cluster. In order to fully
      comprehend the genetic diversity of  cold-tolerant local germplasm in this
      species, germplasm should be collected  from the heterogeneous environments along
      the northern regions of this species'  distribution. The germplasm that we
      collected should be a valuable resource for Saccharum breeding.

PMID- 22614353
TI  - Differential expression  analysis of porcine MDH1, MDH2 and ME1 genes in adipose 
      tissues.
AB  - Malate  dehydrogenases 1 and 2 (MDH1 and MDH2), and malic enzyme 1 (ME1)  play
      important roles in the Krebs cycle for energy metabolism. The mRNA  abundance
      changes of MDH1, MDH2 and ME1 genes were  measured across six different adipose
      tissues from the leaner Landrace and  fatty Rongchang pig breeds using
      quantitative real-time PCR. The mRNA of MDH1, MDH2 and ME1 was more abundant in
      fatty Rongchang pigs than in  leaner Landrace pigs. In both breeds, females
      exhibited higher adipocyte volume  and mRNA abundance of MDH1, MDH2 and ME1
      compared with  males. These values were higher in the subcutaneous adipose tissue
      compared  with visceral adipose tissue. Furthermore, mRNA abundance changes of
      MDH1, MDH2 and ME1 have the remarked significant positive correlation  with
      adipocyte volume across the six adipose tissue types. We conclude that  there are
      breed-, gender- and tissue-specific expression patterns of ME1, MDH1 and MDH2,
      which highlight their potential as candidate genes  for selecting for fat volume
      in pigs.

PMID- 22614355
TI  - Absence of SH2B3 mutation in nonobese diabetic mice.
AB  - Type 1 diabetes is a chronic progressive autoimmune  disease characterized by
      mononuclear cell infiltration, with subsequent  destruction of insulin-producing
      beta-cells. Studies have identified strong associations  between type 1 diabetes
      and several chromosome regions, including 12q24.  Association between type 1
      diabetes and 12q24 arises from SNP rs3184504;  rs3184504 is a nonsynonymous SNP
      in exon 3 of SH2B3 (also known as LNK).  Nonobese diabetic (NOD) mice
      recapitulate many aspects of the pathogenesis of  type 1 diabetes in humans and
      are therefore frequently used in studies  addressing the cellular and molecular
      mechanisms of this disease. It is of  interest to know whether there is a similar
      mutation of SH2B3 in NOD  mice. We found that the SH2B3 mutation is absent in NOD
      mice. To our knowledge,  this is the first report of the sequence and the protein
      levels of SH2B3 in NOD  mice.

PMID- 22614354
TI  - Characterization of Trypanosoma brucei gambiense variant  surface glycoprotein
      LiTat 1.5.
AB  - At present, all available diagnostic antibody  detection tests for Trypanosoma
      brucei gambiense human African  trypanosomiasis are based on predominant variant
      surface glycoproteins (VSGs),  such as VSG LiTat 1.5. During investigations
      aiming at replacement of the  native VSGs by recombinant proteins or synthetic
      peptides, the sequence of VSG  LiTat 1.5 was derived from cDNA and direct N
      terminal amino acid sequencing.  Characterization of the VSG based on cysteine
      distribution in the amino acid  sequence revealed an unusual cysteine pattern
      identical to that of VSG Kinu 1  of T. b. brucei. Even though both VSGs lack the
      third of four conserved  cysteines typical for type A N-terminal domains, they
      can be classified as type  A.

PMID- 22614356
TI  - Genetic diversity analysis of  isolates of the fungal bean pathogen
      Pseudocercospora griseola from  central and southern Brazil.
AB  - Planting  resistant varieties is the most effective control measure against the
      angular  leaf spot of dry beans, a fungal disease caused by Pseudocercospora
      griseola.  However, dry bean varieties with durable resistance are not easily
      obtained.  Knowledge about the genetic variability of the pathogen population is
      key for  the success of dry bean breeding programs aimed at developing resistant 
      materials, but finding suitable operationally simple and genetically accurate 
      markers is not an easy task. The aim of this study was to assess the  suitability
      of the ISSR-PCR technique to quantify the genetic variability of P.  griseola
      isolates. Total DNA of 27 P. griseola isolates from Goias,  Minas Gerais,
      Espirito Santo, and Parana States was extracted and amplified  using specific
      primers for ISSR. Using cluster analysis, 27 genotypes were  identified. The ISSR
      PCR technique was suitable for assessing intraspecific  variability of P.
      griseola. The ISSR-PCR marker was found to be highly  sensitive to genetic
      variation and can aid in elucidating the genetic structure  of the population of
      this plant pathogen as a support tool for the dry bean  breeding programs.

PMID- 22614357
TI  - Multivariate analysis to determine the genetic  distance among backcross papaya
      (Carica papaya) progenies.
AB  - Morpho-agronomic and molecular (RAPD and ISSR markers)  data were used to
      evaluate genetic distances between papaya backcross progenies  in order to help
      identify agronomically superior genotypes. Thirty-two papaya  progenies were
      evaluated based on 15 morpho-agronomic characteristics, 20 ISSR  and 19 RAPD
      primers. Manhattan, Jaccard and Gower distances were used to  estimate
      differences based on continuous and binary data and combined analyses, 
      respectively. Except for production, there were significant differences in the 
      continuous variables among the genotypes. The molecular analysis revealed 193 
      dominant markers (ISSR and RAPD), being 53 polymorphic loci. Among the various 
      clusters that were generated, the one based on a combined analysis of  morpho
      agronomic and molecular data gave the highest cophenetic correlation  (0.72)
      compared to individual analysis, consistently allocating the progenies  into six
      groups. We found that the Gower algorithm was more coherent in the 
      discrimination of the genotypes, demonstrating that a combination of molecular 
      and agronomic data is valuable for studies of genetic dissimilarity in papaya.

PMID- 22614358
TI  - Development and characterization of microsatellite  markers for the endangered
      Chinese yew Taxus chinensis var. mairei (Taxaceae).
AB  - We isolated and characterized 11 microsatellite loci  for the Chinese yew, Taxus
      chinensis var. mairei, an endangered  tree species in China, by constructing a
      (CA)(12)-enriched library. The number of alleles  per locus ranged from 5 to 10.
      The observed heterozygosities ranged from 0.2500  to 0.8333 and the expected
      heterozygosities ranged from 0.5196 to 0.8680. No  significant linkage
      disequilibrium was detected at these loci. However, four  loci significantly
      deviated from Hardy-Weinberg equilibrium. The null alleles  were found to be
      present at locus Tach9 and locus Tach11 by the Micro-checker  test (P < 0.001).
      These polymorphic loci could be employed in research of  gene flow and spatial
      genetic patterns of T. chinensis var. mairei.

PMID- 22614359
TI  - Development of genetic markers for Ochradenus  arabicus (Resedaceae), an endemic
      medicinal plant of Saudi Arabia.
AB  - Some species of the genus Ochradenus are  difficult to identify based on
      morphological markers. Similar limitations are  found for biochemical markers. We
      developed genetic markers based on DNA  sequences for Ochradenus arabicus, which
      is an endemic plant to Saudi  Arabia, locally utilized as a medicinal shrub. The
      internal transcribed spacer  sequence of nuclear ribosomal DNA and chloroplast
      (rpoB and rpoC1)  markers were more informative than other chloroplast DNA
      markers. Based  on these markers, we were able to discriminate this species from
      another  species of the same genus (O. baccatus) that is widely distributed in 
      Saudi Arabia, despite a high degree of morphological similarity. These genetic 
      markers facilitate its identification, even when acquired in a dried state from 
      local markets.

PMID- 22614360
TI  - Regulation of calbindin-D(28k) expression by Msx2 in the dental epithelium.
AB  - Amelogenesis involves the coordinated expression of a set of molecules that
      includes enamel matrix proteins and calcium-binding proteins. Msx2 is a member of
      the divergent homeobox gene family and is instrumental in dental morphogenesis
      and biomineralization. This study focused on an EF-hand calcium-binding protein,
      calbindin-D(28k), which is highly expressed in dental epithelium. In vivo data
      showed that calbindin-D(28k) levels were higher in ameloblasts from Msx2(+/-)
      mice than Msx2(+/+) mice. Consistent with this finding, calbindin-D(28k)
      distribution was affected in transgenic mice with ectopic expression in root
      epithelium in rests of Malassez in Msx2(+/-) and more clearly in Msx2(-/-) mice.
      In accordance with these in vivo data, calbindin-D(28k) protein and mRNA levels
      were decreased in LS8 ameloblast-like cells by exogenous Msx2 overexpression.
      Furthermore, calbindin-D(28k) promoter activity (nt-1075/+34) was specifically
      diminished in the presence of Msx2 overexpression, showing that Msx2 behave as a
      transcriptional repressor for calbindin-D(28k) gene expression. In conclusion,
      Msx2 may control the spatiotemporally restricted frame of calbindin-D(28k)
      production in the dental epithelium in relation to enamel mineralization, as
      previously shown for amelogenin.

PMID- 22614361
TI  - Optimization of a histopathological biomarker for sphingomyelin accumulation in
      acid sphingomyelinase deficiency.
AB  - Niemann-Pick disease (types A and B), or acid sphingomyelinase deficiency, is an
      inherited deficiency of acid sphingomyelinase, resulting in intralysosomal
      accumulation of sphingomyelin in cells throughout the body, particularly within
      those of the reticuloendothelial system. These cellular changes result in
      hepatosplenomegaly and pulmonary infiltrates in humans. A knockout mouse model
      mimics many elements of human ASMD and is useful for studying disease
      histopathology. However, traditional formalin-fixation and paraffin embedding of
      ASMD tissues dissolves sphingomyelin, resulting in tissues with a foamy cell
      appearance, making quantitative analysis of the substrate difficult. To optimize
      substrate fixation and staining, a modified osmium tetroxide and potassium
      dichromate postfixation method was developed to preserve sphingomyelin in epon
      araldite embedded tissue and pulmonary cytology specimens. After processing, semi
      thin sections were incubated with tannic acid solution followed by staining with
      toluidine blue/borax. This modified method provides excellent preservation and
      staining contrast of sphingomyelin with other cell structures. The resulting high
      resolution light microscopy sections permit digital quantification of
      sphingomyelin in light microscopic fields. A lysenin affinity stain for
      sphingomyelin was also developed for use on these semi-thin epon sections.
      Finally, ultrathin serial sections can be cut from these same tissue blocks and
      stained for ultrastructural examination by electron microscopy.

PMID- 22614362
TI  - Comparative analysis of five-year survival results of laparoscopy-assisted
      gastrectomy versus open gastrectomy for advanced gastric cancer: a case-control
      study using a propensity score method.
AB  - BACKGROUND: The aim of this study was to investigate the surgical and oncologic
      outcomes of laparoscopy-assisted gastrectomy (LAG) and open gastrectomy (OG) for
      advanced gastric cancer (AGC) using the case-control method with a sufficient
      follow-up period. PATIENTS AND METHODS: The authors retrospectively analyzed 89
      patients who underwent LAG and 345 patients who underwent OG for AGC between
      August 1999 and June 2007. A total of 176 matched cases were included in the
      final analysis. RESULTS: Except for tumor size and reconstruction, there were no
      statistically significant differences in the clinicopathological parameters
      between the two groups. Although operation time was significantly longer for LAG
      than OG (228.3 vs. 183.6 min, p < 0.0001), first flatus time and postoperative
      hospital stay without complications were significantly shorter in the LAG group
      (3.2 vs. 3.7 days, p < 0.0001; 7.0 vs. 10.4 days, p < 0.0001, respectively).
      Operation-related complications occurred in 7 cases (8.0%) in both groups. 13
      patients (14.8%) in the LAG group and 15 patients (17.1%) in the OG group had
      recurrence. There was no statistically significant difference in the 5-year and
      disease-free survival rates between LAG and OG. CONCLUSIONS: LAG for AGC might be
      considered to be a minimally invasive surgery in some selected cases, although a
      well-designed prospective study comparing LAG with OG for AGC is needed.

PMID- 22614363
TI  - Chemical abstractions.

PMID- 22614371
TI  - Proton conduction: hopping along hydrogen bonds.

PMID- 22614372
TI  - Flow chemistry: a light touch to a deadly problem.

PMID- 22614373
TI  - Self-repairing polymers: materials that heal themselves.

PMID- 22614374
TI  - Enzyme mimics: halogen and chalcogen team up.

PMID- 22614375
TI  - Asymmetric catalysis: the power of pairing.

PMID- 22614376
TI  - Fluorescent sensors: bright ideas.

PMID- 22614377
TI  - Alkaloid synthesis: indolizidines with ease.

PMID- 22614378
TI  - The gold-sulfur interface at the nanoscale.
AB  - Thiolate-protected gold surfaces and interfaces, relevant for self-assembled
      monolayers of organic molecules on gold, for passivated gold nanoclusters and for
      molecule-gold junctions, are archetypal systems in various fields of current
      nanoscience research, materials science, inorganic chemistry and surface science.
      Understanding this interface at the nanometre scale is essential for a wide range
      of potential applications for site-specific bioconjugate labelling and sensing,
      drug delivery and medical therapy, functionalization of gold surfaces for
      sensing, molecular recognition and molecular electronics, and gold nanoparticle
      catalysis. During the past five years, considerable experimental and theoretical
      advances have furthered our understanding of the molecular structure of the gold
      sulfur interface in these systems. This Review discusses the recent progress from
      the viewpoint of theory and computations, with connections to relevant
      experiments.

PMID- 22614379
TI  - Metal-organic frameworks with dynamic interlocked components.
AB  - The dynamics of mechanically interlocked molecules such as rotaxanes and
      catenanes have been studied in solution as examples of rudimentary molecular
      switches and machines, but in this medium, the molecules are randomly dispersed
      and their motion incoherent. As a strategy for achieving a higher level of
      molecular organization, we have constructed a metal-organic framework material
      using a [2]rotaxane as the organic linker and binuclear Cu(II) units as the
      nodes. Activation of the as-synthesized material creates a void space inside the
      rigid framework that allows the soft macrocyclic ring of the [2]rotaxane to
      rotate rapidly, unimpeded by neighbouring molecular components. Variable
      temperature (13)C and (2)H solid-state NMR experiments are used to characterize
      the nature and rate of the dynamic processes occurring inside this unique
      material. These results provide a blueprint for the future creation of solid
      state molecular switches and molecular machines based on mechanically interlocked
      molecules.

PMID- 22614380
TI  - The mechanism of proton conduction in phosphoric acid.
AB  - Neat liquid phosphoric acid (H(3)PO(4)) has the highest intrinsic proton
      conductivity of any known substance and is a useful model for understanding
      proton transport in other phosphate-based systems in biology and clean energy
      technologies. Here, we present an ab initio molecular dynamics study that
      reveals, for the first time, the microscopic mechanism of this high proton
      conductivity. Anomalously fast proton transport in hydrogen-bonded systems
      involves a structural diffusion mechanism in which intramolecular proton transfer
      is driven by specific hydrogen bond rearrangements in the surrounding
      environment. Aqueous media transport excess charge defects through local hydrogen
      bond rearrangements that drive individual proton transfer reactions. In contrast,
      strong, polarizable hydrogen bonds in phosphoric acid produce coupled proton
      motion and a pronounced protic dielectric response of the medium, leading to the
      formation of extended, polarized hydrogen-bonded chains. The interplay between
      these chains and a frustrated hydrogen-bond network gives rise to the high proton
      conductivity.

PMID- 22614381
TI  - Multiphase design of autonomic self-healing thermoplastic elastomers.
AB  - The development of polymers that can spontaneously repair themselves after
      mechanical damage would significantly improve the safety, lifetime, energy
      efficiency and environmental impact of man-made materials. Most approaches to
      self-healing materials require the input of external energy, healing agents,
      solvent or plasticizer. Despite intense research in this area, the synthesis of a
      stiff material with intrinsic self-healing ability remains a key challenge. Here,
      we show a design of multiphase supramolecular thermoplastic elastomers that
      combine high modulus and toughness with spontaneous healing capability. The
      designed hydrogen-bonding brush polymers self-assemble into a hard-soft
      microphase-separated system, combining the enhanced stiffness and toughness of
      nanocomposites with the self-healing capability of dynamic supramolecular
      assemblies. In contrast to previous self-healing polymers, this new system
      spontaneously self-heals as a single-component solid material at ambient
      conditions, without the need for any external stimulus, healing agent,
      plasticizer or solvent.

PMID- 22614382
TI  - Ion-paired chiral ligands for asymmetric palladium catalysis.
AB  - Conventional chiral ligands rely on the use of a covalently constructed, single
      chiral molecule embedded with coordinative functional groups. Here, we report a
      new strategy for the design of a chiral ligand for asymmetric transition-metal
      catalysis; our approach is based on the development of an achiral cationic
      ammonium-phosphine hybrid ligand paired with a chiral binaphtholate anion. This
      ion-paired chiral ligand imparts a remarkable stereocontrolling ability to its
      palladium complex, which catalyses a highly enantioselective allylic alkylation
      of alpha-nitrocarboxylates. By exploiting the possible combinations of the
      achiral onium entities with suitable coordinative functionalities and readily
      available chiral acids, this approach should contribute to the development of a
      broad range of metal-catalysed, stereoselective chemical transformations.

PMID- 22614384
TI  - Light-triggered self-construction of supramolecular organic nanowires as metallic
      interconnects.
AB  - The construction of soft and processable organic material able to display
      metallic conduction properties-a large density of freely moving charges-is a
      major challenge for electronics. Films of doped conjugated polymers are widely
      used as semiconductor devices, but metallic-type transport in the bulk of such
      materials remains extremely rare. On the other hand, single-walled carbon
      nanotubes can exhibit remarkably low contact resistances with related large
      currents, but are intrinsically very difficult to isolate and process. Here, we
      describe the self-assembly of supramolecular organic nanowires between two
      metallic electrodes, from a solution of triarylamine derivative, under the
      simultaneous action of light and electric field triggers. They exhibit a
      combination of large conductivity values (>5 * 10(3) S m(-1)) and a low interface
      resistance (<2 * 10(-4) Omega m). Moreover, the resistance of nanowires in series
      with metal interfaces systematically decreases when the temperature is lowered to
      1.5 K, revealing an intrinsic metallic behaviour.

PMID- 22614383
TI  - Engineering methylaspartate ammonia lyase for the asymmetric synthesis of
      unnatural amino acids.
AB  - The redesign of enzymes to produce catalysts for a predefined transformation
      remains a major challenge in protein engineering. Here, we describe the structure
      based engineering of methylaspartate ammonia lyase (which in nature catalyses the
      conversion of 3-methylaspartate to ammonia and 2-methylfumarate) to accept a
      variety of substituted amines and fumarates and catalyse the asymmetric synthesis
      of aspartic acid derivatives. We obtained two single-active-site mutants, one
      exhibiting a wide nucleophile scope including structurally diverse linear and
      cyclic alkylamines and one with broad electrophile scope including fumarate
      derivatives with alkyl, aryl, alkoxy, aryloxy, alkylthio and arylthio
      substituents at the C2 position. Both mutants have an enlarged active site that
      accommodates the new substrates while retaining the high stereo- and
      regioselectivity of the wild-type enzyme. As an example, we demonstrate a highly
      enantio- and diastereoselective synthesis of threo-3-benzyloxyaspartate (an
      important inhibitor of neuronal excitatory glutamate transporters in the brain).

PMID- 22614385
TI  - Biomimetic radical polymerization via cooperative assembly of segregating
      templates.
AB  - Segregation and templating approaches have been honed by billions of years of
      evolution to direct many complex biological processes. Nature uses segregation to
      improve biochemical control by organizing reactants into defined, well-regulated
      environments, and the transfer of genetic information is a primary function of
      templating. The ribosome, wherein messenger RNA is translated into polypeptides,
      combines both techniques to allow for ideal biopolymer syntheses. Herein is
      presented a biomimetic segregation/templating approach to synthetic radical
      polymerization. Polymerization of a nucleobase-containing vinyl monomer in the
      presence of a complementary block copolymer template of low molecular weight
      yields high molecular weight (M(w) up to ~400,000 g mol(-1)), extremely low
      polydispersity (<=1.08) daughter polymers. Control is attained by segregation of
      propagating radicals in discrete micelle cores (via cooperative assembly of
      dynamic template polymers). Significantly reduced bimolecular termination,
      combined with controlled propagation along a defined number of templates, ensures
      unprecedented control to afford well-defined high molecular weight polymers.

PMID- 22614386
TI  - A soluble copper-bipyridine water-oxidation electrocatalyst.
AB  - The oxidation of water to O(2) is a key challenge in the production of chemical
      fuels from electricity. Although several catalysts have been developed for this
      reaction, substantial challenges remain towards the ultimate goal of an
      efficient, inexpensive and robust electrocatalyst. Reported here is the first
      copper-based catalyst for electrolytic water oxidation. Copper-bipyridine-hydroxo
      complexes rapidly form in situ from simple commercially available copper salts
      and bipyridine at high pH. Cyclic voltammetry of these solutions at pH 11.8-13.3
      shows large, irreversible currents, indicative of catalysis. The production of
      O(2) is demonstrated both electrochemically and with a fluorescence probe.
      Catalysis occurs at about 750 mV overpotential. Electrochemical, electron
      paramagnetic resonance and other studies indicate that the catalyst is a soluble
      molecular species, that the dominant species in the catalytically active
      solutions is (2,2'-bipyridine)Cu(OH)(2) and that this is among the most rapid
      homogeneous water-oxidation catalysts, with a turnover frequency of ~100 s(-1).

PMID- 22614387
TI  - Acyclic cucurbit[n]uril molecular containers enhance the solubility and
      bioactivity of poorly soluble pharmaceuticals.
AB  - The solubility characteristics of 40-70% of new drug candidates are so poor that
      they cannot be formulated on their own, so new methods for increasing drug
      solubility are highly prized. Here, we describe a new class of general-purpose
      solubilizing agents-acyclic cucurbituril-type containers-which increase the
      solubility of ten insoluble drugs by a factor of between 23 and 2,750 by forming
      container-drug complexes. The containers exhibit low in vitro toxicity in human
      liver, kidney and monocyte cell lines, and outbred Swiss Webster mice tolerate
      high doses of the container without sickness or weight loss. Paclitaxel
      solubilized by the acyclic cucurbituril-type containers kills cervical and
      ovarian cancer cells more efficiently than paclitaxel alone. The acyclic
      cucurbituril-type containers preferentially bind cationic and aromatic drugs, but
      also solubilize neutral drugs such as paclitaxel, and represent an attractive
      extension of cyclodextrin-based technology for drug solubilization and delivery.

PMID- 22614389
TI  - Ambiguous bromine.

PMID- 22614391
TI  - How to make a gonad: cellular mechanisms governing formation of the testes and
      ovaries.
AB  - Sex determination of the gonad is an extraordinary process by which a single
      organ anlage is directed to form one of two different structures, a testis or an
      ovary. Morphogenesis of these two organs utilizes many common cellular events;
      differences in the timing and execution of these events must combine to generate
      sexually dimorphic structures. In this chapter, we review recent research on the
      cellular processes of gonad morphogenesis, focusing on data from mouse models. We
      highlight the shared cellular mechanisms in testis and ovary morphogenesis and
      examine the differences that enable formation of the two organs responsible for
      the perpetuation of all sexually reproducing species.

PMID- 22614392
TI  - Differential control of efferent sympathetic activity revisited.
AB  - This article reviews 40 years of research (1970-2010) into the capability of the
      efferent sympathetic nervous system to display differential responsiveness.
      Discovered first were antagonistic changes of activity in sympathetic filaments
      innervating functionally different sections of the cardiovascular system in
      response to thermal stimulation. During the subsequent four decades of
      investigation, a multitude of differential sympathetic efferent response patterns
      were identified, ranging from opposing activity changes at the level of multi
      fiber filaments innervating different organs to the level of single fibers
      controlling functionally different structures in the same organ. Differential
      sympathetic responsiveness was shown to be displayed in response to exogenous or
      artificial stimulation of afferent sensory fibers transmitting particular
      exogenous stimuli, especially those activating peripheral nociceptors. Moreover,
      sympathetic differentiation was found to be characteristic of autonomic responses
      to environmental changes by which homeostasis in the broadest sense would be
      challenged. Heat or cold loads or their experimental equivalents, altered
      composition of inspired air or changes in blood gas composition, imbalances of
      body fluid control, and exposure to agents challenging the immune system were
      shown to elicit differential efferent sympathetic response patterns which often
      displayed a high degree of specificity. In summary, autonomic adjustments to
      changes of biometeorological parameters may be considered as representative of
      the capability of the sympathetic nervous system to exert highly specific
      efferent control of organ functions by which bodily homeostasis is maintained.

PMID- 22614393
TI  - Effects of the AMP-activated protein kinase inhibitor compound C on the
      postconditioned rat heart.
AB  - Ischemic postconditioning (IPOC) protects the myocardium from ischemic
      reperfusion injury, improving functional recovery and cell viability. This
      protection is concurrent with stimulation of glycogen breakdown, increased
      mitochondrial ATP synthesis and content, maintenance of reduced-to-oxidized
      glutathione ratio (GSH/GSSG), and decreased oxidative damage. The present study's
      objective was to assess whether these effects are associated with increased
      resistance to mitochondrial permeability transition pore (MPTP) opening. The
      effects of the AMP-activated protein kinase (AMPK) inhibitor, compound C (CC),
      were measured to investigate association with AMPK. Mitochondria removed from
      postconditioned hearts required higher calcium levels to induce MPTP opening.
      Improved functional recovery, increased glycogen mobilization, maintenance of the
      GSH/GSSG ratio, decreased oxidative damage, and increased resistance to MPTP
      opening were abrogated when the hearts were postconditioned in the presence of
      CC, without affecting preservation of cell viability. Although AMPK appears to
      play a role in IPOC, it would not be the major cellular mediator.

PMID- 22614395
TI  - Influence of acoustic waves on supercontinuum generation in photonic crystal
      fibers.
AB  - In this work, the influence of applying acoustic frequencies to photonic crystal
      fibers (PCF) on the supercontinuum (SC) generation is presented. We will show
      numerically the strong influence of coupling modes in PCF in the latest stage of
      SC and simulations of different scenarios of phase math condition between the
      modes.

PMID- 22614396
TI  - Theoretical explanation of enhanced low dose rate sensitivity in erbium-doped
      optical fibers.
AB  - A new theoretical framework is proposed to explain the dose and dose-rate
      dependence of radiation-induced absorption in optical fibers. A first-order
      dispersive kinetics model is used to simulate the growth of the density of color
      centers during an irradiation. This model succeeds in explaining the enhanced low
      dose rate sensitivity observed in certain kinds of erbium-doped optical fiber and
      provides some insight into the physical reasons behind this sensitivity.

PMID- 22614394
TI  - Effect of gentle cutaneous stimulation on heat-induced autonomic response and
      subjective pain intensity in healthy humans.
AB  - The present study examined whether touch influences the autonomic responses and
      subjective pain intensity induced by noxious heat stimulation in humans. Heart
      rate and digital pulse wave were recorded. Heat stimulation was applied to the
      right plantar foot before, during, and after touch. Subjective pain intensity was
      evaluated using a visual analog scale (VAS). Touch was applied over the right
      medial malleolus for 10 min. Two types of touch were employed in a cross-over
      double-blinded randomized manner. When touch was applied with a soft elastomer
      brush, heat-induced autonomic responses attenuated significantly, while VAS
      scores were unchanged. In contrast, touch with a flat disc was ineffective for
      any measurement. Participants hardly perceived a difference in the texture of the
      touching materials. The present study result suggests there are mechanisms in
      conscious humans where some sort of touch inhibits nociceptive transmission into
      autonomic reflex pathways independent of sensation and cognition.

PMID- 22614397
TI  - Mass-specific scattering coefficient for natural minerogenic particle
      populations: particle size distribution effect and closure analyses.
AB  - The relationship between the particulate scattering coefficient (b(p)) and the
      concentration of suspended particulate matter (SPM), as represented by the mass
      specific scattering coefficient of particulates (b(p)*=b(p)/SPM), depends on
      particle size distribution (PSD). This dependence is quantified for minerogenic
      particle populations in this paper through calculations of b(p)* for common
      minerals as idealized populations (monodispersed spheres); contemporaneous
      measurements of b(p), SPM, and light-scattering attributes of mineral particles
      with scanning electron microscopy interfaced with automated image and x-ray
      analyses (SAX), for a connected stream-reservoir system where minerogenic
      particles dominate b(p); and estimates of b(p) and its size dependency (through
      SAX results-driven Mie theory calculations), particle volume concentration, and
      b(p)*. Modest changes in minerogenic PSDs are shown to result in substantial
      variations in b(p)*. Good closure of the SAX-based estimates of b(p) and particle
      volume concentration with bulk measurements is demonstrated. Converging
      relationships between b(p)* and particle size, developed from three approaches,
      were well described by power law expressions.

PMID- 22614398
TI  - Quasi-phase-matched intracavity laser frequency summation.
AB  - The work presents a theoretical analysis of quasi-phase-matched intracavity
      interaction in the constant-intensity approximation at frequencies summing with
      simultaneous regard for the losses and phases of interacting waves. An analytical
      expression for optimum correlation between interacting waves has been received.
      It is shown that, by the choice of optimum values of phase mismatch, pump
      intensity, and phase relationship, it is possible considerably to increase
      conversion efficiency in comparison with the noncavity case. The numerical
      estimation of expected conversion efficacy in conditions of an experiment is
      presented.

PMID- 22614399
TI  - Optimization design of irradiance array for LED uniform rectangular illumination.
AB  - Light-emitting diode (LED) large-scale uniform rectangular illumination has a
      wide range of applications and is usually created by an irradiance superposition
      scheme. Abandoning the traditional method, we propose an approach to generate
      this illumination mode and enhance efficiency. With this method, an independent
      rectangular irradiance distribution is generated by each LED lens unit, and the
      large-scale illumination is obtained by arraying the irradiance distribution. Two
      slim direct-lit LED backlightings with a distance-height ratio of 3 were
      designed. An optical performance with irradiance nonuniformity less than 0.0228
      and efficiency greater than 96% were obtained. Compared with the traditional
      methods, the efficiency is significantly enhanced and the number of the LED units
      is dramatically reduced by this new method.

PMID- 22614400
TI  - Experimental validation of the MODTRAN 5.3 sea surface radiance model using
      MIRAMER campaign measurements.
AB  - Radiometric images taken in mid-wave and long-wave infrared bands are used as a
      basis for validating a sea surface bidirectional reflectance distribution
      function (BRDF) being implemented into MODTRAN 5 (Berk et al. [Proc. SPIE5806,
      662 (2005)]). The images were obtained during the MIRAMER campaign that took
      place in May 2008 in the Mediterranean Sea near Toulon, France. When atmosphere
      radiances are matched at the horizon to remove possible calibration offsets, the
      implementation of the BRDF in MODTRAN produces good sea surface radiance
      agreement, usually within 2% and at worst 4% from off-glint azimuthally averaged
      measurements. Simulations also compare quite favorably to glint measurements. The
      observed sea radiance deviations between model and measurements are not
      systematic, and are well within expected experimental uncertainties. This is
      largely attributed to proper radiative coupling between the surface and the
      atmosphere implemented using the DISORT multiple scattering algorithm.

PMID- 22614401
TI  - High-stability erbium-doped photonic crystal fiber source.
AB  - A single-pass backward configuration superfluorescent fiber source (SFS) based on
      erbium-doped photonic crystal fiber (EDPCF) with a high mean wavelength stability
      was proposed. The EDPCF was used to improve the intrinsic temperature dependence
      of the SFS. Using the optimal EDPCF length of 24.2 m and pump power of 204 mW, a
      20.7 ppm mean wavelength stability of a prototype SFS was demonstrated with
      increased temperature from -40  degrees C to 60  degrees C. The mean wavelength
      had an ultra stability of 10.3 ppm with increased temperature from -20  degrees C
      to 60  degrees C.

PMID- 22614402
TI  - Uniformly thinned optical fibers produced via HF etching with spectral and
      microscopic verification.
AB  - A method for producing uniformly thinned (etched) optical fibers is described,
      which can also be employed to etch optical fibers containing a Bragg grating
      (FBG) uniformly for evanescent-field-based sensing and other applications.
      Through a simple modification of this method, the fabrication of phase-shifted
      FBGs based on uneven etching is also shown. The critical role of how a fiber is
      secured is shown, and the success of the method is illustrated, by differential
      interference contrast microscopy images of uniformly etched FBGs. An etched FBG
      sensor for the monitoring of the refractive index of different glycerin solutions
      is demonstrated.

PMID- 22614403
TI  - Studies of third-order optical nonlinearities and optical limiting of 2, 3
      butanedione dihydrazone.
AB  - 2, 3-butanedione dihydrazone (BDDH) synthesized via chemical route and nonlinear
      optical parameters, such as nonlinear refractive index (n2), nonlinear absorption
      coefficient (beta), third-order nonlinear optical susceptibility (chi(3)), second
      hyperpolarizability (gamma), and optical-limiting behavior were investigated by
      single beam z-scan technique for different concentrations. Synthesized sample
      were irradiated by a Q-switched, frequency doubled Nd:YAG laser and found that n2
      and beta increases linearly with increasing concentration and hence gamma
      decreases linearly. The excited-state absorption cross sections of BDDH were
      found to be larger than ground-state absorption cross sections, and it leads to
      reverse saturable absorption (RSA). The experimental results are well in
      agreement with the theory and also establish BDDH as one of the potential
      candidate materials for optical limiting at 532 nm.

PMID- 22614404
TI  - Preparation and wettability examinations of transparent SiO2 binder-added MgF2
      nanoparticle coatings covered with fluoro-alkyl silane self-assembled monolayer.
AB  - SiO2-added MgF2 nanoparticle coatings with various surface roughness properties
      were formed on fused silica-glass substrates from autoclaved sols prepared at 100
      180  degrees C. To give it hydrophobicity, we treated the samples with fluoro
      alkyl silane (FAS) vapor to form self-assembled monolayers on the nanoparticle
      coating and we examined the wettability of the samples. The samples preserved
      good transparency even after the FAS treatment. The wettability examination
      revealed that higher autoclave temperatures produced a larger average MgF2
      nanoparticle particle size, a larger surface roughness, and a higher contact
      angle and the roll-off angle.

PMID- 22614405
TI  - Wavefront measurements of a laser-induced breakdown spark in still air.
AB  - Experimental measurements of the wavefronts of the light from a laser-induced
      breakdown (LIB) spark in non-moving air are presented and compared to spark
      dimensional data acquired from photographic measurements of the spark. The data
      show that the variation in the spark emitted wavefront between ignitions can be
      directly related to the motion of the spark volumetric centroid. The dominant
      modal components of the emitted wavefront variations are presented, as well as
      quantitative results for the magnitude of the wavefront variations. The results
      are relevant to the use of LIB as a light source for the measurement of optical
      aberrations such as those caused by compressible (i.e., "aero-optic") flows
      around an aircraft in flight, and data are shown indicating that LIB could be
      successfully used to measure the aberrating effect of compressible shear layers
      and boundary layers at typical cruise Mach numbers.

PMID- 22614406
TI  - Development and characterization of piezoelectrically actuated corner cube
      retroreflectors for applications in free-space optical sensor network.
AB  - In this paper, we report the development of an optical sensor network (OSN) based
      on piezoelectrically actuated corner cube retroreflectors (PA-CCRs). PA-CCRs were
      fabricated by microelectromechanical systems processes and assembled by aligning
      horizontally actuated mirrors and vertical side walls in a holder, which allows
      mass production. Fabricated PA-CCRs showed a tilting angle by more than 1.5 deg
      at 5 V bias voltage. A 3 dB cutoff frequency was measured to be in the range of
      3.5 kHz. To show the feasilbility, an OSN was established based on fabricated PA
      CCRs for on-off keying passive transmission links. The results demonstrated data
      transmission at a rate up to 5 kb/s.

PMID- 22614407
TI  - Effective emissivities of isothermal blackbody cavities calculated by the Monte
      Carlo method using the three-component bidirectional reflectance distribution
      function model.
AB  - This paper proposes a three-component bidirectional reflectance distribution
      function (3C BRDF) model consisting of diffuse, quasi-specular, and glossy
      components for calculation of effective emissivities of blackbody cavities and
      then investigates the properties of the new reflection model. The particle swarm
      optimization method is applied for fitting a 3C BRDF model to measured BRDFs. The
      model is incorporated into the Monte Carlo ray-tracing algorithm for isothermal
      cavities. Finally, the paper compares the results obtained using the 3C model and
      the conventional specular-diffuse model of reflection.

PMID- 22614408
TI  - Partially coherent light-emitting diode illumination for video-rate in-line
      holographic microscopy.
AB  - The light of a light-emitting diode or a common thermal source, such as a
      tungsten filament lamp, is known to be quasi-incoherent. We generated partially
      coherent light of these sources with a volume of coherence in the micrometer
      range of 5-100 MUm3 by spatial and spectral filtering. The corresponding degree
      of partial coherence was adapted for microscopic interference setups, such as a
      digital in-line holographic microscope. The practicability of the sources was
      determined by the spectral emittance and the resulting signal-to-noise ratio
      (SNR) of the detector. The microscale coherence in correlation with the SNR and
      its resolution for microscopy were analyzed. We demonstrate how low-light-level,
      non-laser sources enable holographic imaging with a video frame rate (25
      frames/s), an intermediate SNR of 8 dB, and a volume of coherence of 3.4*10(4)
      MUm3. Holograms of objects with a lateral resolution of 1 MUm were achieved using
      a microscope lens (50*/NA=0.7) and a CCD camera featuring a 4-12 bit dynamic
      range.

PMID- 22614409
TI  - Profiling of micrometer-sized laser beams in restricted volumes.
AB  - We present a method for determining the three-dimensional intensity distribution
      of directed laser radiation with micrometer resolution in restricted volumes. Our
      method is based on the incoupling and guiding properties of optical fibers, with
      the current version requiring only a few hundred micrometers across the measuring
      volume. We characterize the performance of the method and experimentally
      demonstrate profiling of micrometer-sized laser beams. We discuss the limiting
      factors and routes toward a further increase of the resolution and beam profiling
      in even more restricted volumes. Finally, as an application example, we present
      profiling of laser beams inside a micro ion trap with integrated optical fibers.

PMID- 22614410
TI  - All-fiber quasi-continuous wave supercontinuum generation in single-mode high
      nonlinear fiber pumped by submicrosecond pulse with low peak power.
AB  - We demonstrate quasi-continuous wave supercontinuum generation in a single-mode
      high-nonlinear fiber (HNLF) in 1.55 MUm band, which is pumped by the amplified
      passively Q-switched submicrosecond pulse. The pump wavelength is in the normal
      dispersion region of HNLF and near to the zero-dispersion wavelength. The broad
      SC spectral range from 1200 to 2260 nm is obtained with the low pump peak power
      of 17.8 W. The 20 dB bandwidth of 922 nm from 1285 to 2207 nm is obtained with
      the assumption that the peak near 1560 nm is filtered. The spectrum density for
      the 20 dB bandwidth is from -27.5 to -7.5 dbm/nm.

PMID- 22614411
TI  - Laminar and blazed type holographic gratings for a versatile soft x-ray
      spectrograph attached to an electron microscope and their evaluation in the 50
      200 eV range.
AB  - Laminar and blazed type holographic varied-line-spacing spherical gratings for
      use in a versatile soft x-ray flat-field spectrograph attached to an electron
      microscope are designed, fabricated, and evaluated. The absolute diffraction
      efficiencies of laminar (or blazed) master and replica gratings at 86.00 degrees 
      incidence evaluated by synchrotron radiation show over 5% (or 8%) in the 50-200
      eV range with the maxima of 22% (or 26%-27%). Also the resolving power evaluated
      by a laser produced plasma source is in excess of 700 at the energy near the K
      emission spectrum of lithium (~55 eV) for all gratings. Moreover, the K emission
      spectrum of metallic Li with high spectral resolution is successfully observed
      with the spectrograph attached to a transmission electron microscope.

PMID- 22614412
TI  - Ultracompact 1*4 TM-polarized beam splitter based on photonic crystal surface
      mode.
AB  - We provide an improved surface-mode photonic crystal (PhC) T-junction waveguide,
      combine it with an improved PhC bandgap T-junction waveguide, and then provide an
      ultracompact 1*4 TM-polarized beam splitter. The energy is split equally into the
      four output waveguides. The maximal transmission ratio of each output waveguide
      branch equals 24.7%, and the corresponding total transmission ratio of the
      ultracompact 1*4 beam splitter equals 98.8%. The normalized frequency of maximal
      transmission ratio is 0.397(2pic/a), and the bandwidth of the ultracompact 1*4 TM
      polarized beam splitter is 0.0106(2pic/a). To the best of our knowledge, this is
      the first time such a high-efficiency 1*4 beam splitter exploiting the
      nonradiative surface mode as a guided mode has been proposed. Although we only
      employed a 1*4 beam splitter, our design can easily be extended to other 1*n beam
      splitters.

PMID- 22614413
TI  - Transfer-matrix method based on a discrete coupling model for analyzing uniform
      and nonuniform codirectional fiber grating couplers.
AB  - A simple and efficient transfer-matrix method based on a discrete coupling model
      is presented to analyze uniform and nonuniform fiber grating couplers between
      copropagating core and cladding modes. Uniform and piecewise-uniform long-period
      gratings were fabricated by a point-by-point arc discharge technique. Their
      measured transmission spectra were compared with the transmission spectra
      calculated by the presented method.

PMID- 22614414
TI  - Resonance asymmetry induced bias errors in waveguide type optical passive
      resonator gyro.
AB  - We present an in-depth analysis of the resonance asymmetry in a silica waveguide
      ring resonator (WRR) and its influence on the waveguide-type optical passive
      resonator gyro (OPRG). A big bias error appears at the output of the OPRG. This
      big error is caused not only by the resonance asymmetry in the WRR, but also by
      the modulation parameters in the phase modulation spectroscopy technique (PMST).
      It has been proved that the bias error is proportional to the modulation
      frequency difference between the clockwise (CW) and counterclockwise (CCW)
      lightwaves. Three types of resonance asymmetries are thoroughly introduced and
      discussed. Methods to overcome the big bias error are demonstrated. A high
      reciprocal resonator is crucial to reduce the bias error. For a certain
      resonator, a proper temperature needs to be set to minimize the resonance
      asymmetry. A proper modulation frequency difference between the CW and CCW
      lightwaves is also helpful to reduce the bias error.

PMID- 22614415
TI  - Axial nanodisplacement measurement based on astigmatism effect of crossed
      cylindrical lenses.
AB  - Spot distortion caused by astigmatism effect in orthogonal cylindrical lenses is
      utilized to measure axial displacement with 30 nm resolution, strong noise
      immunity, and compact experiment setup. Axial displacement of the sample surface
      is determined by four-quadrant difference processing of distorted laser spots'
      energy distribution images received by CCD. Four-quadrant difference processing
      results indicate an applicable measuring range of 5.6 MUm (cubic fitting
      r=0.9988) with a highly linear range of 1.2 MUm (linear fitting r=0.9996).
      Factors affecting measuring range and sensitivity are analyzed by theoretical
      deduction and numerical simulation. This technique has potential applications in
      drifting sample tracking and measurement in advanced microscopy.

PMID- 22614416
TI  - Lensless multiple-image optical encryption based on improved phase retrieval
      algorithm.
AB  - A novel architecture of the optical multiple-image encryption based on the
      modified Gerchberg-Saxton algorithm (MGSA) by using cascading phase only
      functions (POFs) in the Fresnel transform (FrT) domain is presented. This
      proposed method can greatly increase the capacity of the system by avoiding the
      crosstalk, completely, between the encrypted target images. Each present stage
      encrypted target image is encoded as to a complex function by using the MGSA with
      constraining the encrypted target image of the previous stage. Not only the
      wavelength and position parameters in the FrT domain can be keys to increase
      system security, the created POFs are also served mutually as the encryption keys
      to decrypt target image from present stage into next stage in the cascaded
      scheme. Compared with a prior  method [Appl. Opt.48, 2686-2692 (2009)], the main
      advantages of this proposed encryption system is that it does not need any
      transformative lenses and this makes it very efficient and easy to implement
      optically. Simulation results show that this proposed encryption system can
      successfully achieve the multiple-image encryption via fewer POFs, which is more
      advantageous in simpler implementation and efficiency than a prior method where
      each decryption stage requires two POFs to accomplish this task.

PMID- 22614417
TI  - Optical transmittance measurement system for coated elements with low
      transmittance.
AB  - The low-transmittance elements required for a high power laser facility have
      stringent specifications about transmittance. To validate optic performance
      against specifications, a metrology system for transmittance is proposed. The
      system is composed of a laser source, an integrating sphere, a power meter, and
      four uncoated wedged glasses. A relative measurement method is adopted, which is
      that the surface reflectivity of uncoated glass is used as the reference to
      compare with the sample's transmittance. The systematic feature is that uncoated
      wedged glasses are applied to split and reflect beams, which not only avoid
      coating errors, but also make the two beam powers attenuate properly. Measurement
      results for a sample's transmittance are presented. Experiment and analysis show
      that the relative standard uncertainty (sigma(T)/T) of measurement is 0.424%.
      This system is available for large-aperture elements.

PMID- 22614418
TI  - Theoretical modeling and experiment of refractive index change in He+ ion
      implanted KTP waveguide.
AB  - A theoretical model is presented to explain the refractive index change in the
      ion-implanted KTP waveguide, which includes respective contributions of
      spontaneous polarization, molar polarization and molar volume, and photoelastic
      effect. Numerical calculations of refractive indices along different crystalline
      orientations (X, Y, and Z) as a function of the lattice damage level, determined
      by Rutherford back-scattering/channeling technique, are performed based on the
      results from a set of z-cut KTP crystals implanted by 300 keV He+ ions in doses
      ranging from 4*10(16) to 8*10(16) ions/cm2. The theoretical results show
      consistency with the experimental data. To our knowledge, this is the first model
      to comprehensively describe the ion-implanted KTP planar waveguide.

PMID- 22614419
TI  - Calibration method for high-accuracy measurement of long focal length with Talbot
      interferometry.
AB  - In this paper, a new calibration method for accurate long focal-length
      measurements, based on Talbot interferometry, is presented. Error analysis is
      derived in detail by the numerical method, and an effective way to improve the
      accuracy is proposed. By this method, the systematic errors that are the main
      factors effecting accuracy are calibrated and reduced. Both simulation and
      experiments have been carried out to prove the effectiveness and advantages of
      the proposed method as compared to conventional approaches. The experimental
      results reveal that the relative error is lower than 0.02%, and the repeatability
      is better than 0.05%. This method is especially useful for measuring long focal
      length lenses.

PMID- 22614420
TI  - Photonic crystalline IR fibers for the spectral range of 2-40 MUm.
AB  - Monocrystals of Ag(1-x)Tl(x)Br(1-x)I(x) and Ag(1-x)Tl(x)Cl(y)I(z)Br(1-y-z) for
      the spectral range from 2.0 to 40.0 MUm with improved photostability were
      developed and grown. The grown crystals were used for fabrication of single-mode
      IR fibers. Experimental studies of optical properties of these fibers have
      confirmed their single-mode operation at CO2 laser wavelength and demonstrated
      wider mode field for microstructured fiber compared to fibers with conventional
      double-layered structure.

PMID- 22614421
TI  - Flexible structured-light-based three-dimensional profile reconstruction method
      considering lens projection-imaging distortion.
AB  - Structured-light profilometry is a powerful tool to reconstruct the three
      dimensional (3D) profile of an object. Accurate profile acquisition is often
      hindered by not only the nonlinear response (i.e., gamma effect) of electronic
      devices but also the projection-imaging distortion of lens used in the system. In
      this paper, a flexible 3D profile reconstruction method based on a nonlinear
      iterative optimization is proposed to correct the errors caused by the lens
      distortion. It can be easily extended to measurements for which a more complex
      projection-imaging distortion model is required. Experimental work shows that the
      root-mean-square (RMS) error is reduced by eight times and highly accurate
      results with errors of less than 10/00 can be achieved by the proposed method.

PMID- 22614422
TI  - Utilization of frequency information in a linear wavenumber-scanning
      interferometer for profile measurement of a thin film.
AB  - The positions of the front and rear surfaces of a silicon dioxide film with 4 MUm
      thickness is measured with a novel and simple method in which both amplitude and
      phase of a sinusoidal wave signal corresponding to one optical path difference of
      a reflecting surface is utilized in a linear wavenumber-scanning interferometer.
      For this utilization, the scanning width and the position of the reference mirror
      are adjusted exactly to distinguish the two sinusoidal waves corresponding to the
      two surfaces of the film. The scanning width of the wavenumber and wavelength of
      the light source are 0.326*10(-3) nm(-1) and 140 nm, respectively.

PMID- 22614423
TI  - Full-band absorption enhancement in ultrathin-film solar cells through the
      excitation of multiresonant guided modes.
AB  - We demonstrate the optimization of plasmonic thin-film solar cells with broadband
      absorption enhancements. The solar cells model system consists of a three
      dimensional, periodic array of Ag/silica cylinders on a Si film supported by a
      silica substrate. Particle swarm optimization (PSO) and the finite-difference
      time domain (FDTD) are combined to achieve the maximum absorption enhancement
      (Ehm). Through optimization, the optimal system parameters, such as the height
      and diameter of Ag and the silica cylinder, and the period of periodic array,
      were obtained. Following this approach, we can attain a 321% enhancement in the
      integrated quantum efficiency as compared to a cell without metallic structures.
      The full-band absorption enhancement arises from the near-field enhancement and
      multiresonant guided modes in the Si waveguide.

PMID- 22614424
TI  - Optical eye tracking system for noninvasive and automatic monitoring of eye
      position and movements in radiotherapy treatments of ocular tumors.
AB  - A noninvasive eye tracking system based on infrared 3-D video-oculographic
      techniques is proposed for the automatic monitoring of eye position and
      orientation in external beam radiotherapy of ocular tumors. The presented method
      can be applied for the real-time estimation of lesion position and tumor-beam
      misalignments, allowing automatic patient setup and eye movement gated
      treatments. A prototypal eye tracker was developed and tested on five subjects,
      achieving gaze estimation errors of 0.5 degrees  and eye monitoring frequencies
      of 125 Hz. The proposed application can potentially improve quality and efficacy
      of ocular radiotherapy treatments, currently based on invasive, qualitative, and
      manual control procedures.

PMID- 22614425
TI  - Dual-mode surface-plasmon sensor based on bimetallic film.
AB  - We propose a plasmonic structure, based on a silver-gold two-layered metallic
      film, where two surface plasmons (SPs) with equal propagation constants are
      excited simultaneously at different wavelengths. We show theoretically that the
      bimetallic film provides unique opportunities for manipulation of plasmons and
      optimization of the accuracy and cross-sensitivity. The structure can be used as
      an effective self-reference SP sensor in wavelength-interrogated design.

PMID- 22614426
TI  - Image-inpainting and quality-guided phase unwrapping algorithm.
AB  - For the wrapped phase map with regional abnormal fringes, a new phase unwrapping
      algorithm that combines the image-inpainting theory and the quality-guided phase
      unwrapping algorithm is proposed. First, by applying a threshold to the
      modulation map, the valid region (i.e., the interference region) is divided into
      the doubtful region (called the target region during the inpainting period) and
      the reasonable one (the source region). The wrapped phase of the doubtful region
      is thought to be unreliable, and the data are abandoned temporarily. Using the
      region-filling image-inpainting method, the blank target region is filled with
      new data, while nothing is changed in the source region. A new wrapped phase map
      is generated, and then it is unwrapped with the quality-guided phase unwrapping
      algorithm. Finally, a postprocessing operation is proposed for the final result.
      Experimental results have shown that the performance of the proposed algorithm is
      effective.

PMID- 22614427
TI  - Investigation of laser-induced damage by nanoabsorbers at the surface of fused
      silica.
AB  - A model for describing laser-induced damage in optical materials by nanosecond
      laser pulses is investigated. The laser-damage critical fluence is obtained based
      on calculating the light absorption of nanoabsorbers by using Mie theory and
      solving the heat equation. Considering a power law distribution of nano
      absorbers, we calculated the damage probability at the surface of fused silica
      including Pt particles. The theoretical results calculated with appropriate
      parameters are applied to fit the experimental data in order to identify the
      properties of nanodefects.

PMID- 22614428
TI  - Negative-index metamaterial at visible frequencies based on high order plasmon
      resonance.
AB  - A type of negative-index metamaterial composed of periodic arrays of SRRs is
      proposed and numerically investigated in the visible frequencies. Employing the
      high order magnetic resonance to induce negative permeability, negative
      refractive index is obtained between 395 THz and 430 THz with the maximum
      FOM=4.59. The effective permeability exhibits a rapid convergence with increasing
      number of metamaterial layers. Different responses from the electric and magnetic
      resonances to the changing geometric parameters are compared and analyzed in
      terms of the field distribution. Simulation results show that the high order
      magnetic resonance can be greatly enhanced at visible frequencies as well as
      effectively tuned over a wide spectral range without notably altering the
      coupling between unit cells.

PMID- 22614429
TI  - Controlled bistability by using array defect layers in one-dimensional nonlinear
      photonic crystals.
AB  - Using analytical modeling and detailed numerical simulations, we investigate the
      input-output transmission regimes in one-dimensional (1D) nonlinear photonic
      crystal including array defect layers. A coupled-mode system is derived from the
      Maxwell equations and analyzed for the stationary-transmission regime in the new
      proposed structure. Using the idea about introducing defect layers into 1D
      nonlinear photonic crystals, a new method for creating and controlling optical
      bistability is proposed. The periodic optical structures with array defect layers
      can be used as all optical switches between lower- and higher-transmissive
      states, whereas it possesses one jumping from a low-transmissive state to a
      transparent state.

PMID- 22614430
TI  - Three-dimensional Dammann vortex array with tunable topological charge.
AB  - We describe a kind of true 3D array of focused vortices with tunable topological
      charge, called the 3D Dammann vortex array. This 3D Dammann vortex array is
      arranged into the structure of a true 3D lattice in the focal region of a
      focusing objective, and these focused vortices are located at each node of the 3D
      lattice. A scheme based on a Dammann vortex grating (DVG) and a mirror is
      proposed to provide a choice for changing the topological charge of the 3D
      Dammann vortex array. For experimental demonstration, a 5*5*5 Dammann vortex
      array is implemented by combining a 1*7 DVG, a 1*5 Dammann zone plate, and
      another 5*5 Dammann grating. The topological charge of this Dammann vortex array
      can be tuned (from -2 to +2 with an interval of +1) by moving and rotating the
      mirror to select different diffraction orders of the 1*7 DVG as the incident
      beam. Because of these attractive properties, this 3D Dammann vortex array should
      be of high interest for its potential applications in various areas, such as 3D
      simultaneous optical manipulation, 3D parallel vortex scanning microscope, and
      also parallel vortex information transmission.

PMID- 22614431
TI  - Optical compressive change and motion detection.
AB  - Localization information of moving and changing objects, as commonly extracted
      from video sequences, is typically very sparse with respect to the full data
      frames, thus fulfilling one of the basic conditions of compressive sensing
      theory. Motivated by this observation, we developed an optical compressive change
      and motion-sensing technique that detects the location of moving objects by using
      a significantly fewer samples than conventionally taken. We present examples of
      motion detection and motion tracking with over two orders of magnitude fewer
      samples than required with conventional systems.

PMID- 22614433
TI  - Far-field interference from a sphere and its applications.
AB  - A theoretical model of far-field interference from a sphere has been established,
      and its applications have been investigated. When two coherent parallel laser
      beams shine on a smooth sphere surface from opposite directions, the reflected
      lights form interference fringes at far field. The fringes have hyperbolic shapes
      and are not uniformly distributed. This paper derives a method for calculating
      the path-length difference between two parallel reflected lights, analyzes the
      interference field, and discusses reasons that cause the fringe density
      variations. A formula for calculating the highest orders of interference fringes
      is also provided. A method for using a spectrometer, CCD camera, and computer to
      measure the sphere diameter is demonstrated. The results agree with those from an
      Abbe comparator. The theory and methods are also suitable for measuring diameters
      of smooth cylinders.

PMID- 22614432
TI  - 157 W all-fiber high-power picosecond laser.
AB  - An all-fiber high-power picosecond laser is constructed in a master oscillator
      power amplifier configuration. The self-constructed fiber laser seed is passively
      mode locked by a semiconductor saturable absorber mirror. Average output power of
      157 W is obtained after three stages of amplification at a fundamental repetition
      rate of 60 MHz. A short length of ytterbium double-clad fiber with a high doping
      level is used to suppress nonlinear effects. However, a stimulated Raman
      scattering (SRS) effect occurs owing to the 78 kW high peak power. A self-made
      all-fiber repetition rate increasing system is used to octuple the repetition
      rate and decrease the high peak power. Average output power of 156.6 W is
      obtained without SRS under the same pump power at a 480 MHz repetition rate with
      0.6 nm line width.

PMID- 22614434
TI  - Influence of water environment on holmium laser ablation performance for hard
      tissues.
AB  - This study clarifies the ablation differences in air and in water for hard
      biological tissues, which are irradiated by fiber-guided long-pulsed holmium
      lasers. High-speed photography is used to record the dynamic characteristics of
      ablation plumes and vaporization bubbles induced by pulsed holmium lasers. The
      ablation morphologies and depth of hard tissues are quantitatively measured by
      optical coherence microscopy. Explosive vaporization effects in water play a
      positive role in the contact ablation process and are directly responsible for
      significant ablation enhancement. Furthermore, water layer depth can also
      contribute to ablation performance. Under the same laser parameters for fiber
      tissue contact ablation in air and water, ablation performances are comparable
      for a single-laser pulse, but for more laser pulses the ablation performances in
      water are better than those in air. Comprehensive knowledge of ablation
      differences under various environments is important, especially in medical
      procedures that are performed in a liquid environment.

PMID- 22614435
TI  - Inpatient statin use predicts improved ischemic stroke discharge disposition.
AB  - OBJECTIVE: To determine whether statin use is associated with improved discharge
      disposition after ischemic stroke. METHODS: We used generalized ordinal logistic
      regression to analyze discharge disposition among 12,689 patients with ischemic
      stroke over a 7-year period at 17 hospitals in an integrated care delivery
      system. We also analyzed treatment patterns by hospital to control for the
      possibility of confounding at the individual patient level. RESULTS: Statin users
      before and during stroke hospitalization were more likely to have a good
      discharge outcome (odds ratio [OR] for discharge to home = 1.38, 95% confidence
      interval [CI] 1.25-1.52, p < 0.001; OR for discharge to home or institution =
      2.08, 95% CI 1.72-2.51, p < 0.001). Patients who underwent statin withdrawal were
      less likely to have a good discharge outcome (OR for discharge to home = 0.77,
      95% CI 0.63-0.94, p = 0.012; OR for discharge to home or institution = 0.43, 95%
      CI 0.33-0.55, p < 0.001). In grouped-treatment analysis, an instrumental variable
      method using treatment patterns by hospital, higher probability of inpatient
      statin use predicted a higher likelihood of discharge to home (OR = 2.56, 95% CI
      1.71-3.85, p < 0.001). In last prior treatment analysis, a novel instrumental
      variable method, patients with a higher probability of statin use were more
      likely to have a good discharge outcome (OR for each better level of ordinal
      discharge outcome = 1.19, 95% CI 1.09-1.30, p = 0.001). CONCLUSIONS: Statin use
      is strongly associated with improved discharge disposition after ischemic stroke.

PMID- 22614436
TI  - Is asymptomatic hemorrhagic transformation really innocuous?

PMID- 22614437
TI  - Teaching neuroimages: bilateral subperiosteal hemorrhage of the orbit.

PMID- 22614438
TI  - Teaching neuroimages: leptomeningeal and pachymeningeal enhancement in a patient
      with spontaneous CSF leak.

PMID- 22614439
TI  - Effects of low-intensity pulsed ultrasound on osteosarcoma and cancer cells.
AB  - Metastatic bone tumors cause pain and pathological fractures due to bone
      destruction. If we could enhance new osteogenic activities and prevent
      progression of osteolytic change by malignant cells, patients could achieve
      satisfactory activity of daily living. Low-intensity pulsed ultrasound (LIPUS),
      which leads to bone formation by osteoblasts, has been used for the treatment of
      fractures. LIPUS has been reported to enhance the effect of an anticancer drug on
      lymphoma and liver cancer cells. However, there have been no reports of
      proliferation, vascularization and migration effects on cancer cells. In this
      study, we investigated the effects of LIPUS treatment on cancer and osteosarcoma
      cells and specifically whether it promotes bone formation without accelerating
      proliferation of tumor cells. We used MC3T3-E1 cells, a mouse osteoblast cell
      line, LM8, a mouse osteosarcoma cell line, SaOS2, a human osteosarcoma cell line,
      786-O, a human renal cancer cell line, PC-3, a human prostate cancer cell line,
      and A549, a human lung cancer cell line. The expression of extracellular signal
      regulated kinase (ERK1/2), Akt, beta-catenin, vascular endothelial growth factor
      (VEGF), and cell migration were analyzed. LIPUS stimulation did not affect
      proliferation of all the cells examined. The phosphorylation of ERK1/2 and Akt
      was induced by LIPUS stimulation in MC3T3-E1, LM8, SaOS2 and A549 cells, but not
      in PC-3 and 786-O cells. LIPUS stimulation did not significantly increase beta
      catenin. VEGF protein levels and cell migration were significantly increased only
      in MC3T3-E1 cells. It may be concluded that LIPUS stimulation on metastatic bone
      tumors induces differentiation of osteoblasts without proliferation of tumor
      cells. Our study suggests that LIPUS may be a new method of treatment without
      surgery for metastatic bone tumors.

PMID- 22614442
TI  - Fluorescence monitoring of ionic liquid-facilitated biopolymer mobilization and
      reorganization.
AB  - Ionic liquid-facilitated mobilization and reorganization of biopolymers in
      natural fibrous materials is visualized by confocal fluorescent
      spectromicroscopy. Ionic liquid-based processes controllably fuse adjacent fibres
      while simultaneously leaving selected amounts of biopolymers in their native
      states. These processes generate congealed materials with extended intermolecular
      hydrogen bonding networks and enhanced properties.

PMID- 22614440
TI  - Cancer in inflammatory bowel disease:  lessons from animal models.
AB  - PURPOSE OF REVIEW: Human colitis-associated cancers (CAC) represent a
      heterogeneous group of conditions in which multiple oncogenic pathways are
      involved. In this article, we review the latest studies using genetic, chemical,
      bacterial and innate immune-mediated experimental models of CAC. RECENT FINDINGS:
      Using the azoxymethane-dextran sodium sulfate model, wound healing pathways seem
      to be required in the development of CAC. There is also an emerging understanding
      that commensal and/or pathogenic bacteria can promote tumorigenesis, through T
      cell and TLR-mediated inflammation. Using specific transgenic mice (villin-CD98,
      T cell SMAD7, villin-TLR4) or specific knockout mice, investigators have
      determined that derangements in epithelial or innate and adaptive immune pathways
      can result in CAC. Subtle perturbations in epithelial repair - both too little or
      too exuberant - can render mice susceptible to tumorigenesis. SUMMARY: With the
      aid of animal models, we have witnessed a rapid expansion of our knowledge of the
      molecular and immunologic mechanisms underlying inflammatory cancers. Though
      animal models have contributed a discrete amount of information to our
      understanding of tumorigenesis in the setting of intestinal inflammation, it is
      clear that no single animal model will be able to adequately recapitulate the
      pathogenesis of complex colorectal cancers, but each model gets us one step
      closer to comprehending the nature of CAC.

PMID- 22614441
TI  - Photoelectron spectroscopy of the model GFP chromophore anion.
AB  - A photoelectron spectroscopy study of the anionic model chromophore of the green
      fluorescent protein is presented. From the photoelectron spectra taken at 3.496
      eV, 4.62 eV, and 6.15 eV the vertical and adiabatic detachment energies are
      determined to be 2.8 +/- 0.1 eV and 2.6 +/- 0.2 eV, respectively. The vertical
      detachment energy is higher than the S1<- S0 absorption maximum (2.57 eV) and
      indicates that the S1 state is bound with respect to electron detachment in the
      Franck-Condon region. The photoelectron spectrum taken at 6.15 eV, together with
      TD-DFT calculations, are used to assign a number of excited states in the neutral
      radical that correspond to electron loss from occupied orbitals in the anion. The
      photoelectron spectrum at 2.58 eV shows evidence for electrons formed by
      thermionic emission, suggesting that internal conversion is the dominant
      relaxation pathway following S1<- S0 excitation. 

PMID- 22614443
TI  - Primary urethral carcinoma in females: an epidemiologic study on demographical
      factors, histological types, tumour stage and survival.
AB  - PURPOSE: To obtain insight into demographical factors, histology and survival
      rates of females diagnosed with primary urethral cancer and to determine
      favourable treatment. METHODS: Data from 91 females with primary urethral
      carcinoma, age varying from 15 to 85 years, registered between 1989 and 2008 at
      the National Cancer Registry of the Netherlands were used for this study.
      Demographical factors, incidence rate, morphology and tumour stage according to
      TNM classification were analysed. Kaplan-Meier survival curves were constructed
      and stratified by stage, histological type and treatment modality. RESULTS: The
      overall crude annual incidence was 0.7 per million women with a peak incidence in
      the age group of 80-84 years. Analysis of the morphology showed urothelial cell
      carcinoma (UCC) in 45 %, squamous cell carcinoma (SCC) in 19 %, adenocarcinoma
      (AC) in 29 %, and unknown or undifferentiated carcinoma accounted for 6 %. Almost
      half of patients (46 %) had advanced disease at time of diagnosis and was mainly
      treated with surgery and/or radiotherapy. The 5-year survival rates of stage 0
      II, stage III and stage IV were 67, 53 and 17 %, respectively. The 5-year
      survival rates of SCC, UCC and AC were 64, 61 and 31 %, respectively.
      CONCLUSIONS: Female primary urethral carcinoma is a rare condition, and the
      majority of patients were aged above 65 years. Almost half of patients have
      advanced disease upon diagnosis. TNM stage and histological type of disease are
      the most determining factors for survival. Extended surgery with or without
      radiotherapy seems to be the most favourable treatment. Awareness and early
      diagnosis are important to improve survival.

PMID- 22614445
TI  - Renal tubular dysfunction and lactic acidosis.

PMID- 22614444
TI  - Ureteral tumours showing a worse prognosis than renal pelvis tumours may be
      attributed to ureteral tumours more likely to have hydronephrosis and less likely
      to have haematuria.
AB  - PURPOSE: To demonstrate the relationships among tumour location, hydronephrosis,
      and tumour stage in patients with Upper Urinary Tract Urothelial Carcinoma (UUT
      UC). Moreover, we want to determine whether primary tumour location is an
      independent predictor of prognosis in those patients. METHODS: Retrospective
      analysis of 251 UUT-UC patients from our centre treated with radical
      nephroureterectomy between 2000 and 2010. Patients who had previous radical
      cystectomy, preoperative chemotherapy, previous contralateral UUT-UC, multifocal
      tumours, or metastatic disease at presentation were excluded. Overall, 217
      patients were then available for evaluation. The relationships among tumour
      location, hydronephrosis, and tumour stage were analysed. Tumour location was
      categorized as renal pelvis or ureter. Progression-free survival (PFS) and cancer
      specific survival (CSS) probabilities were estimated using Kaplan-Meier and Cox
      regression analyses. RESULTS: Tumour location was renal pelvis in 146 cases (67
      %), ureter in 71 cases (33 %). Median follow-up was 52 months. Compared with
      renal pelvic tumours, ureteral tumours were more likely to have hydronephrosis
      and to be associated with advanced stages (p < 0.001), but less likely to have
      haematuria. The 5-year CSS estimate was 79.3 % for renal pelvic tumours and 64.7
      % for ureteral tumours (p = 0.03). The 5-year PFS probability was 68.7 % for
      renal pelvic tumours and 54.2 % for ureteral tumours (p = 0.02). On univariable
      and multivariable analysis, tumour location was an independent prognostic factor
      for CSS (p < 0.05). CONCLUSIONS: Ureteral tumours were associated with a worse
      prognosis than renal pelvis tumours. The possible hypothesis may be due partially
      to that ureteral tumours are more likely to have hydronephrosis and less likely
      to have haematuria.

PMID- 22614447
TI  - Aldose reductase regulates platelet-derived growth factor-induced proliferation
      through mediating cell cycle progression in rat mesangial cells.
AB  - Aldose reductase (AR), the first and the rate-limiting enzyme of the polyol
      pathway, has been implicated in platelet-derived growth factor (PDGF)-induced
      proliferation of rat mesangial cells (MsCs). It is well known that AR plays an
      important role in various chronic diabetic complications, for example, diabetic
      nephropathy. Moreover, our previous studies have demonstrated that an AR
      inhibitor (ARI) significantly reduced the proliferation of rat MsCs induced by
      PDGF, however, the mechanism remains unclear. The aim of the present study was to
      elucidate the molecular mechanisms through which AR regulates PDGF-induced rat
      MsC proliferation. It was demonstrated that PDGF-induced MsC proliferation was
      significantly inhibited by pretreatment with ARI. Cell cycle analysis by flow
      cytometry revealed that ARI prevented the entry of cells from the G1 into the S
      phase. Furthermore, the effect of the PI3K/Akt signaling pathway on the cell
      cycle was analyzed. The PI3K/Akt pathway was activated with PDGF treatment.
      However, ARI blocked Akt activation in response to PDGF. Moreover, PDGF increased
      the levels of p21Cip1 cyclin kinase inhibitor protein in MsC, which was markedly
      inhibited by pretreatment with ARI. Conversely, PDGF significantly reduced the
      levels of the p27Kip1 cyclin kinase inhibitor protein, which was also restored by
      pretreatment with ARI. In conclusion, AR is involved in PDGF-induced rat MsC
      proliferation, and may serve as a potential target for the inhibition of MsC
      proliferation in several types of glomerulonephritis.

PMID- 22614448
TI  - Mathematical model for glucose regulation in the whole-body system.
AB  - The human body needs continuous and stable glucose supply for maintaining its
      biological functions. Stable glucose supply comes from the homeostatic regulation
      of the blood glucose level, which is controlled by various glucose consuming or
      producing organs. Therefore, it is important to understand the whole-body glucose
      regulation mechanism. In this article, we describe various mathematical models
      proposed for glucose regulation in the human body, and discuss the difficulty and
      limitation in reproducing real processes of glucose regulation.

PMID- 22614449
TI  - Diaminobenzene schiff base, a novel class of DNA minor groove binder.
AB  - Molecules that target the deoxyribonucleic acid (DNA) minor groove are relatively
      sequence specific and they can be excellent carrier structures for cytotoxic
      chemotherapeutic compounds which can help to minimize side effects. Two novel
      isomeric derivatives of diaminobenzene Schiff base [N,N'-bis (2-hydroxy-3
      methoxybenzylidene)-1,2-diaminobenzene (2MJ) and N,N'-bis(2-hydroxy-3
      methoxybenzylidene)-1,3-diaminobenzene (2MH)] were analyzed for their DNA minor
      groove binding (MGB) ability using viscometry, UV and fluorescence spectroscopy,
      computational modeling and clonogenic assay. The result shows that 2MJ and 2MH
      are strong DNA MGBs with the latter being more potent. 2MH can form interstrand
      hydrogen bond linkages at its oxygens with N3 of adenines. Changing the 2-hydroxy
      3-methoxybenzylidene binding position to the 1,3 location on the diaminobenzene
      structure (2MJ) completely removed any viable hydrogen bond formation with the
      DNA and caused significant decrease in binding strength and minor groove binding
      potency. Neither compound showed any significant cytotoxicity towards human
      breast, colon or liver cancer cell lines.

PMID- 22614450
TI  - BOA detoxification of four summer weeds during germination and seedling growth.
AB  - A recent greenhouse study revealed a significant reduction of germination and
      growth of redroot pigweed (Amaranthus retroflexus) and common purslane (Portulaca
      oleracea) by rye mulch, whereas velvetleaf (Abutilon theophrasti) and common
      lambsquarters (Chenopodium album) were not suppressed. Since BOA detoxification
      by metabolic alteration may influence the relation between the benzoxazinoid
      content of the soil mulch and weed suppression, we tested the dynamics in BOA
      detoxification in different plant organs of three and 10-day-old seedlings of
      four warm season weeds incubated with five BOA concentrations (4, 20, 40, 80, and
      200 MUmol g(-1) fresh weight). In addition, germination and length of 3-day-old
      seedlings were measured after exposure to 0, 0.3, 1.5, 3, 6, and 15 MUmol BOA.
      Finally, we tested the influence of the MDR translocator inhibitors verapamil,
      nifedipine, and the GST inhibitor ethycrynic acid on BOA accumulation and
      detoxification activity. Due to BOA-detoxification, all weeds were able to grow
      in environments with low BOA contents. At higher contents, Abutilon theophrasti
      and Chenopodium album had a better chance to survive because of highly active
      mechanisms that avoided the uptake of BOA (A. theophrasti) and of efficient
      detoxification activities in youngest seedlings (C. album). The interpretation of
      all of the data gave the following sequence of increasing sensitivity: A.
      theophrasti <<< C. album << P. oleracea <= A. retroflexus. The results were in
      agreement with recent findings of the suppression of these weeds by rye mulches
      and their benzoxazinoid contents. Our studies demonstrate for the first time that
      the detoxification of BOA influences the survival of certain weeds in
      environments enriched with this allelochemical. Therefore, detoxification
      processes affect the potential for weed suppression by soil allelochemicals in
      sustainable weed management.

PMID- 22614451
TI  - Influence of hydroxypropyl-beta-cyclodextrin on phytosterol biotransformation by
      different strains of Mycobacterium neoaurum.
AB  - Cyclodextrins (CDs) can improve productivity in the biotransformation of steroids
      by increasing conversion rate, conversion ratio, or substrate concentration.
      However, little is known of the proportion of products formed by multi-catabolic
      enzymes, e.g., via sterol side chain cleavage. Using three strains with different
      androst-1,4-diene-3,17-dione (ADD) to androst-4-ene-3,17-dione (AD) ratios,
      Mycobacterium neoaurum TCCC 11028 (MNR), M. neoaurum TCCC 11028 M1 (MNR M1), and
      M. neoaurum TCCC 11028 M3 (MNR M3), we found that hydroxypropyl-beta-cyclodextrin
      (HP-beta-CD) can appreciably increase the ratio of ADD to AD, the reaction rate,
      and the molar conversion. In the presence of HP-beta-CD, conversion of 0.5 g/L of
      phytosterol (PS) was 2.4, 2.4, and 2.3 times higher in the MNR, MNR M1, and MNR
      M3 systems, respectively, than in the controls. The ADD proportion increased by
      38.4, 61.5, and 5.9 % compared with the control experiment, which resulted in a
      strong shift in the ADD/AD ratio in the ADD direction. Our results imply that the
      three PS-biotransforming strains cause efficient side chain degradation of PS,
      and the increased conversion of PS when using HP-beta-CD may be associated with
      the higher PS concentration in each case. A similar solubilizing effect may not
      induce a prominent influence on the ADD/AD ratio. However, the different
      activities of the Delta1-dehydrogenase of PS-biotransforming strains result in
      different incremental percentage yields of ADD and ADD/AD ratio in the presence
      of HP-beta-CD.

PMID- 22614452
TI  - Microwave radiation and reactor design influence microbial communities during
      methane fermentation.
AB  - The effect of reactor design and method of heating on the efficiency of methane
      fermentation and composition of microbial communities, especially methanogenic
      Archaea, were determined. The research was carried out using submerge- and
      trickling-bed reactors fed with wastewater and the heat supply into the reactors
      included a convection heating method and microwave radiation. The polymerase
      chain reaction-denaturing gradient gel electrophoresis and relative real-time PCR
      were used in order to assess the biofilm communities. The best fermentation
      results and the highest abundance of methanogenic Archaea in biomass were
      observed in microwave heated trickling-bed reactors. The research proved that in
      reactors of identical design, the application of microwaves enabled a higher
      fermentation efficiency to be obtained and simultaneously increased the diversity
      of methanogenic Archaea communities that favors process stability. All the
      identified sequences of Archaea belonged to Methanosarcina sp., suggesting that
      species from this genera are susceptible to non-thermal effects of microwaves.
      There were no effects from microwaves on the bacterial communities in both types
      of reactors, however, the bacterial species composition varied in the reactors of
      different design.

PMID- 22614453
TI  - Alternaric acid stimulates  phosphorylation of His-tagged RiCDPK2, a calcium
      dependent protein kinase in  potato plants.
AB  - Calcium-dependent protein kinases (CDPK) are an essential component of plant
      defense mechanisms against pathogens. We investigated the effect of alternaric
      acid, a host-specific toxin produced by the plant fungal pathogen Alternaria
      solani (Pleosporaceae), on a putative plasma membrane and cytosolic kinase
      RiCDPK2 of potato (Solanum tuberosum) and on hypersensitive cell death of host
      potato cells. Alternaric acid, in the presence of Ca2+ and Mg2+, stimulated in
      vitro phosphorylation of His-tagged RiCDPK2, a Ca2+-dependent protein kinase
      found in potato plants. We concluded that Ca2+ and Mg2+ play an important role in
      the interaction between alternaric acid and RiCDPK2. Based on our observations,
      alternaric acid regulates RiCDPK2 kinase during the infection process in an
      interaction between host and A. solani, leading to the inhibition of
      hypersensitive cell death in the host. We suggest that alternaric acid is a
      primary determinant by which A. solani stimulates CDPK activity in the host,
      suppressing hypersensitive cell death.

PMID- 22614454
TI  - Differences in numbers of  termicins expressed in two termite species affected by
      fungal contamination of  their environments.
AB  - Termicin is a defensin-like antimicrobial peptide of  termites that has strong
      antifungal activity. Fifty-six different termicin  mRNAs encoding 46 different
      peptides were amplified and identified from Odontotermes  formosanus
      (Termitidae), a species that inhabits environments with a large  variety of
      microbial fauna. In contrast, only 38 different termicin mRNAs  encoding 21
      different peptides were amplified and identified from Reticulitermes  chinensis
      (Rhinotermitidae). All mRNAs were amplified by reverse transcript  PCR, with
      primers designed from reported termicin mRNA sequences. All of these  genes
      showed high intraspecific sequence identity and were found to be highly 
      homologous with other reported termicin genes. These two termite species live  in
      different environments; the latter encounters relatively fewer pathogens in  its
      habitat. We conclude that differences in microenvironmental pressure can  affect
      the number of termicin genes expressed in termite species.

PMID- 22614455
TI  - Correlation of Y-chromosome multiple  segmental deletions and chromosomal
      anomalies in non-obstructive azoospermic males from  northeastern China.
AB  - We investigated the frequency and types of Y-chromosome  microdeletions and
      chromosomal anomalies in non-obstructive azoospermic and  severely
      oligozoospermic infertile males in northeastern China. The sample  consisted of
      519 infertile males (456 azoospermic, 63 severely  oligozoospermic). PCR assays
      for Y-chromosome microdeletions and chromosome  analysis were performed on all
      patients and controls. Array-comparative genomic  hybridization was performed for
      three patients with chromosomal anomalies.  Fifty-nine of 519 patients (11.37%)
      had Y-chromosome microdeletions. Microdeletions  were found in 11.18% (51/456) of
      the non-obstructive azoospermic patients and  in 12.7% (8/63) of the severely
      oligozoospermic patients. Eleven of 51  non-obstructive azoospermic patients with
      Y-chromosome microdeletions had  multiple segmental deletions in the AZFb+c
      regions; four of these patients had  chromosomal anomalies. Our sample from
      northeastern China had a higher  frequency of microdeletions among severely
      oligozoospermic than among  non-obstructive azoospermic males.

PMID- 22614456
TI  - Genetic correlations between  mature cow weight and productive and reproductive
      traits in Nellore cattle.
AB  - We  investigated genetic associations between mature cow weight (MW) and weaning 
      weight (WW), yearling weight (YW), weight gain from birth to weaning (GBW), 
      weight gain from weaning to yearling (GWY), weaning hip height (WHH), yearling 
      hip height (YHH), scrotal circumference (SC), and age at first calving (AFC). 
      Data from 127,104 Nellore animals born between 1993 and 2006, belonging to 
      Agropecuaria Jacarezinho Ltda., were analyzed. (Co)variance components were 
      obtained by the restricted maximum likelihood method, applying an animal model 
      in a multi-traits analysis. The model included direct genetic and residual 
      effects as random effects, the fixed effects of contemporary group, and the 
      linear and quadratic effects of animal age at recording (except for AFC, GBW, 
      and GWY) and age of cow at calving as covariates (except for MW). The numbers  of
      days from birth to weaning and from weaning to yearling were included as 
      covariates for GBW and GWY, respectively. Estimated direct heritabilities were 
      0.43 +/- 0.02 (MW), 0.33 +/- 0.01 (WW), 0.36 +/- 0.01 (YW), 0.28 +/- 0.02 (GBW),
      0.31 +/-  0.01 (GWY), 0.44 +/- 0.02 (WHH), 0.48 +/- 0.02 (YHH), 0.44 +/- 0.01
      (SC), and 0.16 +/-  0.03 (AFC). Genetic correlations between MW and productive
      traits were positive  and of medium to high magnitude (ranging from 0.47 +/- 0.03
      to 0.71 +/- 0.01). A  positive and low genetic correlation was observed between
      MW and SC (0.24 +/-  0.04). A negative genetic correlation (-0.19 +/- 0.03) was
      estimated between MW  and AFC. Selection to increase weight or weight gains at
      any age, as well as  hip height, will change MW in the same direction. Selection
      for higher SC may  lead to a long-term increase in MW. The AFC can be included in
      selection  indices to improve the reproductive performance of beef cattle without
      significant changes in MW.

PMID- 22614457
TI  - Genotyping of urinary samples stored with EDTA for  forensic applications.
AB  - Individual identification of urinary samples is  necessary when sample switching
      or handling are suspected during a judicial  process. To improve the rate of
      successful genotyping of urinary samples, we  examined the stability of DNA in
      urinary samples stored for up to 30 days.  Urinary samples from 20 healthy
      individuals (10 males and 10 females) were  stored at -80 degrees C with
      different concentrations of EDTA (0, 10 and 40 mM).  Urinary DNA was extracted at
      days 0, 3, 9, and 30 after collection. The  Quantifiler Human DNA Quantification
      Kit was used for measuring DNA  concentration. Twenty STR loci were co-amplified
      using amelogenin-specific PCR  with the Goldeneye 20A Kit. Significant
      differences in DNA concentration were  observed between samples from females and
      males. In the case of female urinary DNA  preservation with 10 and 40 mM EDTA the
      mean detection rate reached 0.95 after  up to 30 days; for the male urinary
      samples, the mean detection rate of urinary  DNA preserved with 40 mM EDTA was
      significantly higher than with 10 mM. We  concluded that 40 mM EDTA is the best
      concentration for preservation of the DNA  in urinary samples.

PMID- 22614458
TI  - Morphological traits and RAPD  markers for characterization and identification of
      minor Spanish olive  cultivars from the Extremadura region.
AB  - A total  of 91 wild olive accessions and 31 olive cultivars growing in the
      Extremadura  region of central-western Spain were analyzed using morphological
      traits and RAPD  markers. We focused on three main and 16 minor Spanish olive
      cultivars that are  recognized as native or local to the Extremadura region. The
      five arbitrary  10-mer primers tested on the olive cultivars gave 67 polymorphic
      bands,  representing 91% of the total amplification products. The number of bands
      per  primer ranged from 9 to 18, whereas the number of polymorphic bands ranged
      from  8 to 17. All the cultivars could be identified by a combination of three 
      primers (OPF-6, OPA-8, and OPK-16); four cultivar-specific markers were 
      detected. The minor local "Jariego" and "Tempranillo" cultivars showed the most 
      distal similarities. The resulting dendrogram, using the unweighted pair-group 
      method with arithmetic mean clustering algorithm, depicted the pattern of 
      relationships between the local Extremadura cultivars and the cultivars from 
      geographically connected regions. This analysis showed a correlation between 
      most of the minor local cultivars and the geographical origin; there was no 
      apparent clustering according to morphological traits or fruit use of olive 
      cultivars when these parameters were used as analysis criteria.

PMID- 22614459
TI  - Characterization and  bacterial-binding activity of a novel C-type lectin from
      the red-spotted  grouper, Epinephelus akaara.
AB  - Because of their specific binding to carbohydrates, lectins play a crucial role
      in pathogen recognition and clearance in vertebrate animals. Previously, only two
      types of collectins had been isolated from bony fish: mannan-binding lectin (MBL)
      and galactose-binding lectin (GalBL). We sequenced a novel collectin (designated
      EALec1) from the red-spotted grouper, Epinephelus akaara. The gene structure of
      EALec1 and the alignment of the carbohydrate recognition domain of the three
      collectins demonstrated that EALec1 is a new type of collectin derived from MBL.
      We examined the expression pattern of the EALec1 transcripts in 12 tissues of the
      red-spotted grouper. The EALec1 gene was found to have multiple copies; their
      transcripts were detected in all 12 tissues. EALec1 was also recombined and
      expressed in Escherichia coli to investigate its immune functions and
      carbohydrate-binding characterization. We concluded that EALec1 belongs to the
      mannan-binding lectin group, despite its different Ca2+-dependent sites in the
      carbohydrate recognition domain, and that it is involved in the recognition and
      clearance of invaders in the red-spotted grouper.

PMID- 22614461
TI  - Abstracts of IOF Regionals, the 1st Latin America Osteoporosis Meeting. Sao
      Paulo, Brazil. May 24-27, 2012.

PMID- 22614460
TI  - Common variants in the CRP gene  are associated with serum C-reactive protein
      levels and body mass index in  healthy individuals in Mexico.
AB  - Variants in the C-reactive protein (CRP) gene have been found to be associated
      with various phenotypic traits. We evaluated the effect of four SNPs in the CRP
      gene on serum levels of protein and body mass index (BMI) in 150 unrelated
      Mexican subjects from 18 to 25 years old, without hypertension, non-overweight,
      and without inflammatory diseases, non-smoking and non-consumers of alcohol.
      Subjects were measured for BMI, waist circumference, blood pressure, and serum
      glucose and triglycerides. The identification of SNPs was performed by PCR-RFLP.
      Three of the four SNPs were associated with variation in serum levels of CRP,
      increased in TT (rs1130864) and GG (rs2794521) genotypes, and decreased in the AA
      genotype of rs1205. The TT genotype was associated with a significant increase in
      BMI (beta = 1.1 kg/m2, P = 0.04). Two haplotypes were significantly associated
      with increased serum levels of CRP, but not with BMI. We conclude that variation
      in the CRP gene affects serum protein levels.

PMID- 22614463
TI  - Temporal distance and discrimination: an audit study in academia.
AB  - Through a field experiment set in academia (with a sample of 6,548 professors),
      we found that decisions about distant-future events were more likely to generate
      discrimination against women and minorities (relative to Caucasian males) than
      were decisions about near-future events. In our study, faculty members received e
      mails from fictional prospective doctoral students seeking to schedule a meeting
      either that day or in 1 week; students' names signaled their race (Caucasian,
      African American, Hispanic, Indian, or Chinese) and gender. When the requests
      were to meet in 1 week, Caucasian males were granted access to faculty members
      26% more often than were women and minorities; also, compared with women and
      minorities, Caucasian males received more and faster responses. However, these
      patterns were essentially eliminated when prospective students requested a
      meeting that same day. Our identification of a temporal discrimination effect is
      consistent with the predictions of construal-level theory and implies that subtle
      contextual shifts can alter patterns of race- and gender-based discrimination.

PMID- 22614462
TI  - Direct catalytic asymmetric synthesis of highly functionalized (2
      ethynylphenyl)alcohols via Barbas-List aldol reaction: scope and synthetic
      applications.
AB  - A high-yielding asymmetric synthesis of functionalized (2-ethynylphenyl)alcohols
      5/6 with good diastereo- and enantioselectivities was achieved by Barbas-List
      aldol (BLA) reaction of 2-alkynylbenzaldehydes 1 with various ketones 2 in the
      presence of trans-4-OH-L-proline or L-prolinamide derivative 3/4 as catalyst at
      the ambient temperature or -35  degrees C. This method also gives first time
      access to the novel double aldol addition compounds 6, which are of medicinal
      importance. Chiral functionalized (2-ethynylphenyl)alcohols 5/6 were transformed
      into acyclic and cyclic 1,4-triazoles 8/9 and cis-1,3-diols 10 in good yields
      with high selectivity through double click-reaction and Lewis acid-mediated
      NaBH(4) reduction respectively. Chiral products 8-10 may become good ligands and
      inhibitors in medicinal chemistry.

PMID- 22614465
TI  - Novel mixed anion [trans-Pt(C[triple bond, length as m-dash]CTol)(2)(CN)(2)](2-)
      as a building block of new luminescent Pt(II)-Tl(I) and Pt(II)-Pb(II)
      coordination polymers.
AB  - A new class of heteroleptic blue emitter anion, [trans-Pt(C[triple bond, length
      as m-dash]CTol)(2)(CN)(2)](2-), has been prepared and successfully used in the
      assembling of luminescent supramolecular heterometallic PtTl(2) and PtPb(2)
      species.

PMID- 22614466
TI  - Public-private partnership as a solution for integrating genetic services into
      health care of countries with low and middle incomes.
AB  - In recent years scientific progress has dramatically raised the potential of
      genetic services, but the actual benefits of these developments are not
      universally shared. In countries of low and middle incomes, improvements in
      genetic services frequently lag behind. Since this is generally caused by lack of
      resources and not by the lack of political will, the question arises, how can one
      most easily acquire the necessary capital to improve the health care in these
      areas. Public-private partnerships (PPPs) offer one approach to solve this issue,
      aiming at the inclusion of private enterprises in the realisation of public
      authority services. So far PPPs have been used exclusively in other health
      service areas. In this paper a first attempt is being made to discuss the
      feasibility of transferring the concept of PPP to genetic services, and
      consideration is given as to where the most promising starting point might be. We
      start by defining a multilevel structure that needs to be considered in providing
      comprehensive genetic care. We continue by explaining the concept of PPPs and
      their current types of implementation in medical services. We then examine how
      the PPP model could be applied to genetic services or sections thereof. We arrive
      at the conclusion that a likely starting point for PPP in genetic services is at
      the level of the infrastructure building service. 

PMID- 22614468
TI  - Lowest-order axial and ring mode lasing in confocal quasi-stadium laser diodes.
AB  - We investigated the lasing modes of quasi-stadium laser diodes that have confocal
      cavity geometries, with stripe electrode contacts formed either along the cavity
      axis or a diamond-shaped trajectory. It was clearly demonstrated that by using
      narrow electrode contact patterns of 2 MUm width, the lowest-order axial and ring
      modes were excited selectively. On the other hand, the second-lowest-order axial
      and ring modes were excited by using broad electrode patterns of 14 MUm width.
      Experimentally obtained far-field patterns for lasers with broad and narrow
      electrode contact patterns agree very well with the simulation results obtained
      using an extended Fox-Li mode calculation method.

PMID- 22614467
TI  - Molecular cytogenetic studies in strepsirrhine primates, Dermoptera and
      Scandentia.
AB  - Since the first chromosome painting study between human and strepsirrhine
      primates was performed in 1996, nearly 30 species in Strepsirrhini, Dermoptera
      and Scandentia have been analyzed by cross-species chromosome painting. Here, the
      contribution of chromosome painting data to our understanding of primate genome
      organization, chromosome evolution and the karyotype phylogenetic relationships
      within strepsirrhine primates, Dermoptera and Scandentia is reviewed. Twenty-six
      to 43 homologous chromosome segments have been revealed in different species with
      human chromosome-specific paint probes. Various landmark rearrangements
      characteristic for each different lineage have been identified, as cytogenetic
      signatures that potentially unite certain lineages within strepsirrhine primates,
      Dermoptera and Scandentia.

PMID- 22614469
TI  - Modeling of end-pumped Yb:YAG thin-disk lasers with nonuniform temperature
      distribution.
AB  - A plane wave model with nonuniform temperature distribution in the thin-disk
      crystal is developed to describe the dynamic behavior of an end-pumped Yb:YAG
      thin-disk laser. A set of couple-rate equations and 2D stationary heat-conduction
      equations are derived. The stable temperature distribution in the disk crystal is
      calculated using a numerical iterative method. The analytic expression is capable
      of dealing with more practical laser systems than previous works on this subject
      as it allows for nonuniform temperature distribution in the disk crystal. Based
      on these results, we examined laser output intensity as a function of pump
      intensity, dopant concentration, resonator coupler reflectivity, crystal
      thickness and temperature of cooling liquid.

PMID- 22614470
TI  - Integrated fiber optic incoherent broadband cavity enhanced absorption
      spectroscopy detector for near-IR absorption measurements of nanoliter samples.
AB  - An integrated fiber-optic sensor is described that uses incoherent broadband
      cavity enhanced absorption spectroscopy for sensitive detection of aqueous
      samples in nanoliter volumes. Absorption was measured in a 100 um gap between the
      ends of two short segments of multimode graded-index fiber that were integrated
      into a capillary using a precision machined V-grooved fixture that allowed for
      passive fiber alignment. The other ends of the fibers were coated with dielectric
      mirrors to form a 9.5 cm optical resonator. Light from a fiber-coupled
      superluminescent diode was directly coupled into one end of the cavity, and
      transmission was measured using a fiber-coupled silicon photodiode. Dilute
      aqueous solutions of near infrared dye were used to determine the minimum
      detectable absorption change of 2.4*10(-4) under experimental conditions in which
      pressure fluctuations limited performance. We also determined that the absolute
      minimum detectable absorption change would be 1.6*10(-5) for conditions of
      constant pressure in which absorption measurement is limited by electronic and
      optical noise. Tolerance requirements for alignment are also presented.

PMID- 22614471
TI  - Analysis and modeling for fiber-optic gyroscope scale factor based on environment
      temperature.
AB  - To explore and reduce the nonlinear error and temperature dependency of fiber
      optic gyroscope (FOG) scale factor, a scale factor modeling method based on
      temperature is presented in this paper. A hyperbolic curve fitting is proposed
      according to the characteristic of scale factor under stable temperature at
      first. Compared to traditional modeling methods, it shows that a higher precision
      model of scale factor can be obtained. Then the influence of temperature on scale
      factor is analyzed and then the hyperbolic curve fitting method is extended based
      on temperature, making it possible to work over the whole potential temperature
      range of the FOG without degrading the performance. This paper also provides the
      experimental and verification results. It can be seen that a high precision model
      of scale factor has been established, the temperature dependency of scale factor
      has been reduced effectively, and the error due to environment temperature is
      reduced by one order at least.

PMID- 22614472
TI  - Method to measure the second-order birefringence vector distribution along
      optical fibers based on high-speed polarization optical time domain
      reflectometry.
AB  - Based on a high-speed polarization optical domain reflectometry, an innovative
      method to measure the second-order birefringence vector distribution along
      optical fibers was proposed and implemented in this paper. Some interesting data
      were obtained along a 1 km long single mode fiber by only one detection. The
      second-order birefringence magnitude distribution curve can reflect both
      magnitude and direction change information of the first-order birefringence, and
      it was more stable (except the catastrophe points) than that of the first-order.
      The larger variable range of the second-order birefringence magnitude may provide
      a higher sensitivity than the first-order for birefringence-based distributed
      sensors.

PMID- 22614473
TI  - Tunable graphene Q-switched erbium-doped fiber laser with suppressed self-mode
      locking effect.
AB  - Self-mode locking effect in a wideband tunable graphene-based passively Q
      switched erbium-doped fiber laser has been observed experimentally. Q-switching
      is achieved by using graphene as a saturable absorber, while a tunable bandpass
      filter with a narrow bandwidth is used to obtain wideband tunability. We propose
      to suppress the modulation on each pulse from self-mode locking by introducing
      three subring resonators constructed with three 3 dB couplers into the laser ring
      cavity. Moreover, the laser output characteristics with respect to pump power are
      studied in detail. A stable Q-switched erbium-doped fiber laser with a tunable
      range from 1522 nm to 1568 nm is demonstrated experimentally.

PMID- 22614474
TI  - Vicarious calibrations of HICO data acquired from the International Space
      Station.
AB  - The Hyperspectral Imager for the Coastal Ocean (HICO) presently onboard the
      International Space Station (ISS) is an imaging spectrometer designed for remote
      sensing of coastal waters. The instrument is not equipped with any onboard
      spectral and radiometric calibration devices. Here we describe vicarious
      calibration techniques that have been used in converting the HICO raw digital
      numbers to calibrated radiances. The spectral calibration is based on matching
      atmospheric water vapor and oxygen absorption bands and extraterrestrial solar
      lines. The radiometric calibration is based on comparisons between HICO and the
      EOS/MODIS data measured over homogeneous desert areas and on spectral reflectance
      properties of coral reefs and water clouds. Improvements to the present vicarious
      calibration techniques are possible as we gain more in-depth understanding of the
      HICO laboratory calibration data and the ISS HICO data in the future.

PMID- 22614475
TI  - Polarization independent blue-phase liquid crystal cylindrical lens with a
      resistive film.
AB  - We propose a new electrode design for polarization-independent cylindrical lens
      using a polymer-stabilized blue phase liquid crystal (BPLC). The top electrode is
      coated with a transparent and resistive film to generate linearly varying
      electric potential from center to edge; while the bottom iridium tin oxide
      electrode has a constant potential. Therefore, the vertical electric field across
      the BPLC layer varies linearly over the lens aperture and a desired parabolic
      phase profile is obtained automatically according to the Kerr effect. Simulation
      results show that this simple device is polarization independent and it has
      parabolic-like phase profile in a large tuning range.

PMID- 22614476
TI  - Laser heating of uncoated optics in a convective medium.
AB  - Powerful, long-pulse lasers have a variety of applications. In many applications,
      optical elements are employed to direct, focus, or collimate the beam. Typically
      the optic is suspended in a gaseous environment (e.g., air) and can cool by
      convection. The variation of the optic temperature with time is obtained by
      combining the effects of laser heating, thermal conduction, and convective loss.
      Characteristics of the solutions in terms of the properties of the optic
      material, laser beam parameters, and the environment are discussed and compared
      with measurements at the Naval Research Laboratory, employing kW-class, 1 um
      wavelength, continuous wave lasers and optical elements made of fused silica or
      BK7 glass. The calculated results are in good agreement with the measurements,
      given the approximations in the analysis and the expected variation in the
      absorption coefficients of the glasses used in the experiments.

PMID- 22614477
TI  - Automated, portable, low-cost bright-field and fluorescence microscope with
      autofocus and autoscanning capabilities.
AB  - Optical microscopy is a simple, yet essential, imaging technology. Conventional
      laboratory-grade optical microscopes are bulky and costly, confining their use to
      within laboratory settings and restricting their accessibility in regions of
      limited resources. With the aim of overcoming these limitations, we have realized
      a portable, low-cost, and highly automated optical microscope that integrates
      mass-manufactured components, including light-emitting diodes, a web camera,
      optical disk drives, and a microcontroller. Our implementation is capable of
      bright-field and fluorescence imaging with micrometer-scale resolution and
      controlled mechanical actuation of both the lens and sample. We interface the
      lighting, image capture, and mechanical actuators of the microscope into a single
      software environment, enabling automation of common microscope operations, such
      as image focusing and large-area sample visualization. Combination of mechanical
      actuation and software automation into a compact, low-cost microscope system is
      an important initial step toward the goal of making optical microscopy
      universally accessible, portable, and easy to use.

PMID- 22614478
TI  - Characterization of a CH planar laser-induced fluorescence imaging system using a
      kHz-rate multimode-pumped optical parametric oscillator.
AB  - The performance characteristics of a new CH planar laser-induced fluorescence
      (PLIF) imaging system composed of a kHz-rate multimode-pumped optical parametric
      oscillator (OPO) and high-speed intensified CMOS camera are investigated in
      laminar and turbulent CH4-H2-air flames. A multi-channel Nd:YAG cluster that
      produces up to 225 mJ at 355 nm with multiple-pulse spacing of 100 MUs
      (corresponding to 10 kHz) is used to pump an OPO to produce up to 6 mJ at 431 nm
      for direct excitation of the A-X (0, 0) band of the CH radical. Single-shot
      signal-to-noise ratios of 82:1 and 7.5:1 are recorded in laminar premixed flames
      relative to noise in the background and within the flame layer, respectively. The
      spatial resolution and image quality are sufficient to accurately measure the CH
      layer thickness of ~0.4 mm while imaging the detailed evolution of turbulent
      flame structures over a 20 mm span. Background interferences due to polycyclic
      aromatic hydrocarbons and Rayleigh scattering are minimized and, along with
      signal linearity, allow semi-quantitative analysis of CH signals on a shot-to
      shot basis. The effects of design features, such as cavity finesse and passive
      injection seeding, on conversion efficiency, stability, and linewidth of the OPO
      output are also discussed.

PMID- 22614479
TI  - All-optical switch using optically controlled two mode interference coupler.
AB  - In this paper, we have introduced optically controlled two-mode interference
      (OTMI) coupler having silicon core and GaAsInP cladding as an all-optical switch.
      By taking advantage of refractive index modulation by launching optical pulse
      into cladding region of TMI waveguide, we have shown optically controlled
      switching operation. We have studied optical pulse-controlled coupling
      characteristics of the proposed device by using a simple mathematical model on
      the basis of sinusoidal modes. The device length is less than that of previous
      work. It is also seen that the cross talk of the OTMI switch is not significantly
      increased with fabrication tolerances (+/-deltaw) in comparison with previous
      work.

PMID- 22614480
TI  - Surface enhanced absorption and transmission from dye coated gold nanoparticles
      in thin films.
AB  - Absorption spectra of gold nanoisland thin film and the composite film of gold
      having thin coating of Methylene Blue and Rh6G dyes have been studied. Thin gold
      nanoisland film shows surface plasmon resonance (SPR) peak in the visible
      wavelength range, which shifts to near infrared with an increase in the thickness
      of the film. It was found that thin film of gold consists of nanoparticles of
      different size and shape, particularly nanorods of noncylindrical shapes. A
      linear relation was found between SPR peak wavelength and the aspect ratio of the
      nanoparticles in gold thin film. Effective medium refractive index of the gold
      film is estimated to be ~2.5, which decreases with an increase in film thickness.
      The coating of dyes on gold films splits the SPR peak with an enhanced
      absorption. Enhancement in absorption of composite film is maximal when the dye
      absorption peak coincides with the SPR peak; otherwise enhancement in
      transmission is observed for all the wavelength range. Absorption amplitude of
      composite film peaks increase with an increase in the gold film thickness, which
      tend toward saturation for film thickness of >=6 nm. A correlation shows that
      absorption spectra can be described by the Maxwell Garnett theory, when the gold
      nanoparticles have a nearly spherical shape for very thin film (<=6 nm).

PMID- 22614481
TI  - Autofocus for multispectral camera using focus symmetry.
AB  - A multispectral camera acquires spectral color images with high fidelity by
      splitting the light spectrum into more than three bands. Because of the shift of
      focal length with wavelength, the focus of each channel should be mechanically
      adjusted in order to obtain sharp images. Because progressive adjustment is quite
      time consuming, the clear focus must be determined by using a limited number of
      images. This paper exploits the symmetry of focus measure distribution and
      proposes a simple yet efficient autofocus method. The focus measures are computed
      using first-order image derivatives, and the focus curve is obtained by spline
      interpolation. The optimal focus position, which maximizes the symmetry of the
      focus measure distribution, is then computed according to distance metrics. The
      effectiveness of the proposed method is validated in the multispectral camera
      system, and it is also applicable to relevant imaging systems.

PMID- 22614483
TI  - Parallel phase-shifting digital holography with adaptive function using phase
      mode spatial light modulator.
AB  - Parallel phase-shifting digital holography using a phase-mode spatial light
      modulator (SLM) is proposed. The phase-mode SLM implements spatial distribution
      of phase retardation required in the parallel phase-shifting digital holography.
      This SLM can also compensate dynamically the phase distortion caused by optical
      elements such as beam splitters, lenses, and air fluctuation. Experimental
      demonstration using a static object is presented.

PMID- 22614482
TI  - Multi-spatial-frequency and phase-shifting profilometry using a liquid crystal
      phase modulator.
AB  - Optical profilometry is widely applied for measuring the morphology of objects by
      projecting predetermined patterns on them. In this technique, the compact size is
      one of the interesting issues for practical applications. The generation of
      pattern by the interference of coherent light sources has a potential to reduce
      the dimension of the illumination part. Moreover, this method can make fine
      patterns without projection optics, and the illumination part is free of
      restriction from the numerical aperture of the projection optics. In this paper,
      a phase-shifting profilometry is implemented by using a single liquid crystal
      (LC) cell. The LC phase modulator is designed to generate the interference
      patterns with several different spatial frequencies by changing selection of the
      spacing between the micro-pinholes. We manufactured the LC phase modulator and
      calibrated it by measuring the phase modulation amount depending on an applied
      voltage. Our optical profilometry using the single LC cell can generate multi
      spatial frequency patterns as well as four steps of the phase-shifted patterns.
      This method can be implemented compactly, and the reconstructed depth profile is
      obtained without a phase-unwrapping algorithm.

PMID- 22614484
TI  - Spectral optimized asymmetric segmented phase-only correlation filter.
AB  - We suggest a new type of optimized composite filter, i.e., the asymmetric
      segmented phase-only filter (ASPOF), for improving the effectiveness of a
      VanderLugt correlator (VLC) when used for face identification. Basically, it
      consists in merging several reference images after application of a specific
      spectral optimization method. After segmentation of the spectral filter plane to
      several areas, each area is assigned to a single winner reference according to a
      new optimized criterion. The point of the paper is to show that this method
      offers a significant performance improvement on standard composite filters for
      face identification. We first briefly revisit composite filters [adapted, phase
      only, inverse, compromise optimal, segmented, minimum average correlation energy,
      optimal trade-off maximum average correlation, and amplitude-modulated phase-only
      (AMPOF)], which are tools of choice for face recognition based on correlation
      techniques, and compare their performances with those of the ASPOF. We illustrate
      some of the drawbacks of current filters for several binary and grayscale image
      identifications. Next, we describe the optimization steps and introduce the ASPOF
      that can overcome these technical issues to improve the quality and the
      reliability of the correlation-based decision. We derive performance measures,
      i.e., PCE values and receiver operating characteristic curves, to confirm
      consistency of the results. We numerically find that this filter increases the
      recognition rate and decreases the false alarm rate. The results show that the
      discrimination of the ASPOF is comparable to that of the AMPOF, but the ASPOF is
      more robust than the trade-off maximum average correlation height against
      rotation and various types of noise sources. Our method has several features that
      make it amenable to experimental implementation using a VLC.

PMID- 22614485
TI  - Self-adaptive noise suppression for characterizing the dispersion of chirped
      fiber Bragg grating.
AB  - We propose a method to suppress the beat noise generated in fiber low coherence
      interferometry (LCI) systems for characterizing the chromatic dispersion of
      chirped fiber Bragg gratings. The beat noise is considered as the dominant noise
      in the system because of the spectrum mismatch between interference arms due to
      the broad bandwidth of the light source and the introduction of dispersive
      components into the measurement arm, and is unfavorable for the signal quality.
      An experimental system is set up and interferograms of various situations are
      provided. Experiment results indicate that our method is feasible and effective,
      as it improves the signal to noise ratio effectively by a factor of more than 3,
      thereby expanding the measurement range of the LCI system.

PMID- 22614486
TI  - Adaptive affinity propagation with spectral angle mapper for semi-supervised
      hyperspectral band selection.
AB  - Band selection is a commonly used approach for dimensionality reduction in
      hyperspectral imagery. Affinity propagation (AP), a new clustering algorithm, is
      addressed in many fields, and it can be used for hyperspectral band selection.
      However, this algorithm cannot get a fixed number of exemplars during the message
      passing procedure, which limits its uses to a great extent. This paper proposes
      an adaptive AP (AAP) algorithm for semi-supervised hyperspectral band selection
      and investigates the effectiveness of distance metrics for improving band
      selection. Specifically, the exemplar number determination algorithm and
      bisection method are addressed to improve AP procedure, and the relations between
      selected exemplar numbers and preferences are established. Experiments are
      conducted to evaluate the proposed AAP-based band selection algorithm, and the
      results demonstrate that the proposed method outperforms other popular methods,
      with lower computational cost and robust results.

PMID- 22614487
TI  - Measurement of wide frequency range structural microvibrations with a pocket
      digital camera and sub-pixel techniques.
AB  - Analysis of vibrations and displacements is a hot topic in structural
      engineering. Although there is a wide variety of methods for vibration analysis,
      direct measurement of displacements in the mid and high frequency range is not
      well solved and accurate devices tend to be very expensive. Low-cost systems can
      be achieved by applying adequate image processing algorithms. In this paper, we
      propose the use of a commercial pocket digital camera, which is able to register
      more than 420 frames per second (fps) at low resolution, for accurate measuring
      of small vibrations and displacements. The method is based on tracking elliptical
      targets with sub-pixel accuracy. Our proposal is demonstrated at a 10 m distance
      with a spatial resolution of 0.15 mm. A practical application over a simple
      structure is given, and the main parameters of an attenuated movement of a steel
      column after an impulsive impact are determined with a spatial accuracy of 4 um.

PMID- 22614488
TI  - Binary beam splitter.
AB  - We propose a method for designing a diffractive beam splitter that enables the
      diffraction orders to be uniformly distributed within a required elliptic region.
      The performance of the designed optical element is demonstrated experimentally.

PMID- 22614489
TI  - Optical turbulence on underwater image degradation in natural environments.
AB  - It is a well-known fact that the major degradation source on electro-optical
      imaging underwater is from scattering by particles of various origins and sizes.
      Recent research indicates that, under certain conditions, the apparent
      degradation could also be caused by the variations of index of refraction
      associated with temperature and salinity microstructures in the ocean and lakes.
      The combined impact has been modeled previously through the simple underwater
      imaging model. The current study presents the first attempts in quantifying the
      level of image degradation due to optical turbulence in natural waters in terms
      of modulation transfer functions using measured turbulence dissipation rates.
      Image data collected from natural environments during the Skaneateles Optical
      Turbulence Exercise are presented. Accurate assessments of the turbulence
      conditions are critical to the model validation and were measured by two
      instruments to ensure consistency and accuracy. Optical properties of the water
      column in the field were also measured in coordination with temperature,
      conductivity, and depth. The results show that optical turbulence degrades the
      image quality as predicted and on a level comparable to that caused by the
      particle scattering just above the thermocline. Other contributing elements
      involving model closure, including temporal and spatial measurement scale
      differences among sensors and mitigation efforts, are discussed.

PMID- 22614490
TI  - Design of an ultracompact low-power all-optical modulator by means of dispersion
      engineered slow light regime in a photonic crystal Mach-Zehnder interferometer.
AB  - We present the design procedure for an ultracompact low-power all-optical
      modulator based on a dispersion-engineered slow-light regime in a photonic
      crystal Mach-Zehnder interferometer (PhC MZI), selectively infiltrated by
      nonlinear optical fluids. The dispersionless slow-light regime enhancing the
      nonlinearities enabled a 22 MUm long PhC MZI to operate as a modulator with an
      input power as low as 3 mW/MUm. Simulations reveal that the switching threshold
      can be controlled by varying the optofluidic infiltration.

PMID- 22614491
TI  - Optical throughput of the Sagnac interferometer with a modified large optical
      path difference.
AB  - The basic principle of Sagnac interferometer with modified large optical path
      difference is expounded on in this paper. According to the Fresnel formula,
      electromagnetic field energy, and energy flux, the transmittance and reflectance
      of each interface of a Sagnac interferometer are calculated, respectively, and
      then the exact expressions of the optical throughput changing with the incident
      angle, the angle of the incident plane, and paper plane (the bottom plane of
      Sagnac interferometer) and Sagnac interferometer acute angles are given.
      Furthermore, we analyze the effects of various parameters on the optical
      throughput by computer simulation, and some important conclusions are obtained.
      This work is of great scientific significance to the static, real-time
      simultaneous detection of upper atmospheric wind field.

PMID- 22614492
TI  - Diode-pumped 2 MUm vibronic (Tm3+, Yb3+):KLu(WO4)2 laser.
AB  - We report on laser operation in a (6 at. % Tm, 5 at. % Yb):KLu(WO4)2 codoped
      crystal. The vibrational frequencies of KLu(WO4)2 are coupled to the electronic
      transitions of Tm3+ at 1946 nm, creating virtual final laser levels at higher
      energy than the ground level 3H6 of Tm3+. The longest recorded laser wavelength
      was 2039 nm, which is longer than permitted by a pure electronic transition in
      Tm3+ ions in KLu(WO4)2. We show that every laser wavelength can be explained with
      the electron-phonon coupling effect, where the vibration frequencies were
      determined through Raman spectroscopy.

PMID- 22614493
TI  - Gated viewing laser imaging with compressive sensing.
AB  - We present a prototype of gated viewing laser imaging with compressive sensing
      (GVLICS). By a new framework named compressive sensing, it is possible for us to
      perform laser imaging using a single-pixel detector where the transverse spatial
      resolution is obtained. Moreover, combining compressive sensing with gated
      viewing, the three-dimensional (3D) scene can be reconstructed by the time
      slicing technique. The simulations are accomplished to evaluate the
      characteristics of the proposed GVLICS prototype. Qualitative analysis of
      Lissajous-type eye-pattern figures indicates that the range accuracy of the
      reconstructed 3D images is affected by the sampling rate, the image's noise, and
      the complexity of the scenes.

PMID- 22614494
TI  - Visualizing the complex 3D geometry of the perfusion border zone in isolated
      rabbit heart.
AB  - Myocardial infarction, caused by a major blockage of a coronary artery, creates a
      border zone (BZ) between perfused and nonperfused tissue, which is believed to be
      the origin of fatal cardiac arrhythmias. We used a combination of optical
      clearing and polarization-sensitive optical coherence tomography to visualize a
      three-dimensional organization of the BZ in isolated rabbit hearts (n=5) at the
      microscopic level with a high spatial resolution. We found that the BZ has a
      complex three-dimensional structure with nonperfused areas penetrating into
      perfused tissue with finger-like projections. These "fingers" may play an
      important role in the initiation and maintenance of ventricular arrhythmias.

PMID- 22614495
TI  - Numerical simulation of a dual frequency all-optical flip-flop based on a
      nonlinear semiconductor distributed feedback laser structure.
AB  - A new all-optical flip-flop generating light at two different wavelengths lambda1
      (state "a"), or lambda2 (state "b") was suggested. It consists of an active layer
      and a nonlinear wave-guiding layer. Two parallel nonlinear gratings having
      different periods and periodic negative nonlinearities exist along the
      propagation direction in the wave-guiding layer. In state "a," the first grating
      provides the optical feedback for lasing, and the second grating is weak. In
      state "b," due to optical nonlinearity, the first grating weakens, and the second
      one provides the optical feedback for lasing. The refractive index nonlinearity
      is due to the direct absorption of photons at the Urbach tail. The device is
      triggered from state "a" to state "b" and vise versa by input optical pulses of
      wavelengths lambda2 and lambda1, respectively. The time domain simulations show
      switching dynamics in nanosecond time scale.

PMID- 22614496
TI  - High power 2 MHz passively Q-switched nanosecond Nd:YVO4/Cr4+:YAG 914 nm laser.
AB  - We report a high-power, high-repetition-rate end-pumped passively Q-switched
      Nd:YVO4/Cr4+: yttrium aluminum garnet 914 nm laser. The maximum output power of
      3.8 W at 914 nm is achieved at 2 MHz with the absorbed pump power of 25.2 W. The
      highest single pulse energy of a pulsed 914 nm laser reaches 2.3 MUJ with a pulse
      width of 27.1 ns.

PMID- 22614497
TI  - Discrimination between strain and temperature by cascading single-mode thin-core
      diameter fibers.
AB  - A simple fiber-optic sensor capable of discrimination between temperature and
      strain is proposed and experimentally demonstrated. The sensor head is formed by
      cascading two sections of single-mode thin-core diameter fibers (TCFs) that act
      as two different inter-modal interferometers (IMIs). Due to the different
      sensitivity responses of the two IMIs to strain and temperature, it is possible
      to discriminate temperature and strain by monitoring the resonant wavelength
      shifts. The experimental results indicate that the measured strain and
      temperature resolutions are 37.41 MUepsilon and 0.732  degrees C within a strain
      range of 0-1333.3 MUepsilon and a temperature range from 26.9  degrees C to 61.7 
      degrees C. The sensing sensitivities of strain and temperature are -1.03
      pm/MUepsilon and 30.74 pm/ degrees C, respectively. The proposed sensor features
      the advantages of easy fabrication, low cost and high sensitivity, and it
      exhibits great potential in dual-parameter measurement.

PMID- 22614498
TI  - Optical imaging systems analyzed with a 2D template.
AB  - Present determination of optical imaging systems specifications are based on
      performance values and modulation transfer function results carried with a 1D
      resolution template (such as the USAF resolution target or spoke templates). Such
      a template allows determining image quality, resolution limit, and contrast.
      Nevertheless, the conventional 1D template does not provide satisfactory results,
      since most optical imaging systems handle 2D objects for which imaging system
      response may be different by virtue of some not readily observable spatial
      frequencies. In this paper we derive and analyze contrast transfer function
      results obtained with 1D as well as 2D templates.

PMID- 22614499
TI  - Analytical expressions for group-delay dispersion and third-order dispersion of a
      reflection grism-pair compressor.
AB  - We provide a detailed analytical expression of group-delay dispersion (GDD) and
      third-order dispersion (TOD) for a reflection grism-pair compressor without the
      first-order approximation of grating diffraction. The analytical expressions can
      be used to design a grism-pair compressor for compensating the dispersive
      material without ray tracing. Furthermore, the dispersion performance of the
      grism pair compressor, depending on compressor parameters, is comprehensively
      analyzed. Results are shown that we can adjust several parameters to obtain a
      certain GDD and TOD, such as the incidence angle of the beam, refractive index of
      the prism, grating constant, and the separation of the grism pair.

PMID- 22614500
TI  - On the sensitivity of generic porous optical sensors.
AB  - A porous material was considered as a platform for optical sensing. It was
      envisaged that the porous material was infiltrated by a fluid that contains an
      agent to be sensed. Changes in the optical properties of the infiltrated porous
      material provide the basis for detection of the agent to be sensed. Using a
      homogenization approach based on the Bruggeman formalism, wherein the infiltrated
      porous material was regarded as a homogenized composite material, the sensitivity
      of such a sensor was investigated. For the case of an isotropic dielectric porous
      material of relative permittivity epsilon(a) and an isotropic dielectric fluid of
      relative permittivity epsilon(b), it was found that the sensitivity was maximized
      when there was a large contrast between epsilon(a) and epsilon(b); the maximum
      sensitivity was achieved at midrange values of porosity. Especially high
      sensitivities may be achieved for epsilon(b) close to unity when epsilon(a)>>1,
      for example. Furthermore, higher sensitivities may be achieved by incorporating
      pores that have elongated spheroidal shapes.

PMID- 22614501
TI  - Numerical simulation of millisecond laser-induced damage in silicon-based
      positive-intrinsic-negative photodiode.
AB  - An axisymmetric mathematical model was established for millisecond-pulsed Nd:YAG
      laser heating of silicon-based positive-intrinsic-negative photodiode. The
      transient temperature fields were obtained by using the finite element method.
      The temperature dependences of the material parameters and the absorption
      coefficient were taken into account in the calculation. The results indicate that
      the optical absorption coefficient and the thermal conductivity are the two key
      factors for the temperature evolution. The diffusion of boron in the liquid phase
      and the introduction of deep-level defects in the depletion region of the
      photodiode were the two reasons for the millisecond laser-induced electrical
      degradation of the photodiode. The morphological damage threshold and electrical
      degradation threshold of the photodiode were obtained numerically. Meanwhile, the
      influence of the antireflection coating, the doping concentration, and the
      junction depth were also considered. The results show that the morphological
      damage threshold decreases with adding an antireflection coating, the increase of
      the doping concentration, and junction depth. The electrical degradation
      threshold increases only with the junction depth.

PMID- 22614502
TI  - Dark current and noise analyses of quantum dot infrared photodetectors.
AB  - Because the dark current and the noise of quantum dot infrared photodetectors
      (QDIPs) can bring about a degradation in their performance, they have attracted
      more and more attention in recent years. In this paper, an algorithm used to
      evaluate the dark current of the QDIP is proposed, which is based on the
      algorithm including the common contribution of the microscale and the nanoscale
      electron transport. Namely, by accounting for the dependence of the drift
      velocity on the applied electric field, we greatly enhance the accuracy of the
      dark current calculation compared with that in the previous algorithm. This
      proposed algorithm is further used to estimate the noise current of QDIP, and the
      calculated results show a good agreement with the published data.

PMID- 22614503
TI  - Horizon 2020.

PMID- 22614504
TI  - Two centuries of memristors.

PMID- 22614505
TI  - When Brownian diffusion is not Gaussian.

PMID- 22614512
TI  - Material witness: Updating the eureka.

PMID- 22614511
TI  - Colloidal self-assembly: Melting also on cooling.

PMID- 22614513
TI  - X-ray scattering: In tune with organic semiconductors.

PMID- 22614514
TI  - Morphogenesis: Laying down the tracks.

PMID- 22614515
TI  - A stable and real-time nonlinear elastic approach to simulating guidewire and
      catheter insertions based on Cosserat rod.
AB  - Interventional Radiology procedures (e.g., angioplasty, embolization, stent graft
      placement) provide minimally invasive therapy to treat a wide range of
      conditions. These procedures involve the use of flexible tipped guidewires to
      advance diagnostic or therapeutic catheters into a patient's vascular or visceral
      anatomy. This paper presents a real-time physically based hybrid modeling
      approach to simulating guidewire insertions. The long, slender body of the
      guidewire shaft is simulated using nonlinear elastic Cosserat rods, and the
      shorter flexible tip composed of a straight, curved, or angled design is modeled
      using a more efficient generalized bending model. Therefore, the proposed
      approach efficiently computes intrinsic dynamic behaviors of guidewire
      interactions within vascular structures. The efficacy of the proposed method is
      demonstrated using detailed numerical simulations inside 3-D blood vessel
      structures derived from preprocedural volumetric data. A validation study
      compares positions of four physical guidewires deployed within a vascular
      phantom, with the co-ordinates of the corresponding simulated guidewires within a
      virtual model of the phantom. An optimization algorithm is also implemented to
      further improve the accuracy of the simulation. The presented simulation model is
      suitable for interactive virtual reality-based training and for treatment
      planning.

PMID- 22614516
TI  - Quantitative evaluation of transform domains for compressive sampling-based
      recovery of sparsely sampled volumetric OCT images.
AB  - Recently, compressive sampling has received significant attention as an emerging
      technique for rapid volumetric imaging. We have previously investigated
      volumetric optical coherence tomography (OCT) image acquisition using compressive
      sampling techniques and showed that it was possible to recover image volumes from
      a subset of sampled images. Our previous findings used the multidimensional
      wavelet transform as the domain of sparsification for recovering OCT image
      volumes. In this report, we analyzed and compared the potential and efficiency of
      three other image transforms to reconstruct the same volumetric OCT image. Two
      quantitative measures, the mean square error and the structural similarity index,
      were applied to compare the quality of the reconstructed volumetric images. We
      observed that fast Fourier transformation and wavelet both are capable of
      reconstructing OCT image volumes for the orthogonal sparse sampling masks used in
      this report, but with different merits.

PMID- 22614517
TI  - Slip speed feedback for grip force control.
AB  - Grasp stability in the human hand has been resolved by means of an intricate
      network of mechanoreceptors integrating numerous cues about mechanical events,
      through an ontogenetic grasp practice. An engineered prosthetic interface
      introduces considerable perturbation risks in grasping, calling for feedback
      modalities that address the underlying slip phenomenon. In this study, we propose
      an enhanced slip feedback modality, with potential for myoelectric-based
      prosthetic applications, that relays information regarding slip events,
      particularly slip occurrence and slip speed. The proposed feedback modality,
      implemented using electrotactile stimulation, was evaluated in psychophysical
      studies of slip control in a simplified setup. The obtained results were compared
      with vision and a binary slip feedback that transmits on-off information about
      slip detection. The slip control efficiency of the slip speed display is
      comparable to that obtained with vision feedback, and it clearly outperforms the
      efficiency of the on-off slip modality in such tasks. These results suggest that
      the proposed tactile feedback is a promising sensory method for the restoration
      of stable grasp in prosthetic applications.

PMID- 22614518
TI  - A preclinical system prototype for focused microwave thermal therapy of the
      breast.
AB  - A preclinical prototype of a transcutaneous thermal therapy system has been
      developed for the targeted treatment of breast cancer cells using focused
      microwaves as an adjuvant to radiation, chemotherapy, and high-intensity-focused
      ultrasound. The prototype system employs a 2-D array of tapered microstrip patch
      antennas operating at 915 MHz to focus continuous-wave microwave energy
      transcutaneously into the pendent breast suspended in a coupling medium. Prior
      imaging studies are used to ascertain the material properties of the breast
      tissue, and these data are incorporated into a multiphysics model. Time-reversal
      techniques are employed to find a solution (relative amplitudes and phase) for
      focusing at a given location. Modeling tests of this time-reversal focusing
      method have been performed, which demonstrate good targeting accuracy within
      heterogeneous breast tissue. Experimental results using the laboratory prototype
      to perform focused heating in tissue-mimicking gelatin phantoms have demonstrated
      1.5-cm-diameter focal spot sizes and differential heating at the desired focus
      sufficient to achieve an antitumor effect confined to the target region.

PMID- 22614519
TI  - Synergistic effect of malathion and estrogen on mammary gland carcinogenesis.
AB  - Breast cancer is the most frequent malignancy diagnosed in women and is a
      classical model of hormone-dependent malignancy. Over the past 15-20 years,
      epidemiological studies have pointed to an increased breast cancer risk
      associated with prolonged exposure to female hormones. On the other hand,
      environmental chemicals such as malathion, an organophosphorous pesticide used to
      control a wide range of sucking and chewing pests of field crops, may be involved
      in the etiology of breast cancers. Results indicated that estrogen alone
      increased average number of lobules per mm2 of rat mammary glands in comparison
      to control and malathion alone at 30, 124, 240 and 400 days after 5-day
      treatments. On the other hand, malathion alone significantly increased the number
      of ducts in stage of proliferation at 10-240 days after 5-day treatments.
      Furthermore, markers for cancer detection such as mutant p53, c-myc, c-fos and
      CYPs proteins were overexpressed after treatments. Atropine, an anticholinergic
      drug, counteracted these effects when it was combined with malathion under
      similar conditions. The combination of malathion and estrogen synergistically
      increased number of lobules and ducts per mm2 of rat mammary glands after
      treatments and inducing mammary cancer. It can be concluded that combination of
      an environmental substance such as the pesticide malathion and an endogenous
      substance such as estrogen can enhance the deleterious effects in human mammary
      glands inducing cancer and atropine is able to diminish these effects.

PMID- 22614520
TI  - Chagas disease in the immunosuppressed host.
AB  - PURPOSE OF REVIEW: This review examines recent literature on Chagas disease in
      the immunosuppressed host. RECENT FINDINGS: Chagas disease in immunosuppressed
      patients may represent acute transmission in an organ recipient, or reactivation
      of chronic infection in an HIV-infected individual or patient receiving cardiac
      transplantation for Chagas cardiomyopathy. Transplantation of the kidney or liver
      from an infected donor resulted in transmission in 18-19 and 29%, respectively.
      Prospective monitoring usually detects acute infection before symptom onset;
      early treatment is highly effective. In heart transplant patients, reactivation
      symptoms include fever, myocarditis and skin lesions, and may mimic rejection.
      Approximately 20% of HIV- Trypanosoma cruzi infected patients experience
      reactivation; manifestations include meningoencephalitis and/or myocarditis.
      SUMMARY: Transplantation of the heart from a T. cruzi-infected donor is
      contraindicated; use of other organs can be considered. Guidelines recommend
      prospective monitoring rather than prophylactic treatment in recipients.
      Posttransplant monitoring for acute infection or reactivation relies on PCR,
      culture and microscopy of blood specimens regularly for at least 6 months.
      Treatment employs standard courses of benznidazole or nifurtimox, and immune
      reconstitution for the HIV-coinfected patient. Case reports suggest some HIV-T.
      cruzi-infected patients may benefit from secondary prophylaxis, but more data are
      needed to determine efficacy and specific regimens.

PMID- 22614521
TI  - Cytotoxic T lymphocytes for the treatment of viral infections and posttransplant
      lymphoproliferative disorders in transplant recipients.
AB  - PURPOSE OF REVIEW: The continuous and successful expansion of organ transplants
      is unfortunately associated with increased incidence of severe opportunistic
      viral infections and Epstein-Barr virus (EBV)-related lymphomas secondary to
      immunosuppression. Here, we review the strengths and limitations of T-cell-based
      strategies used to treat viral infections in immunocompromised individuals.
      RECENT FINDINGS: While current antiviral drugs are often suboptimal because of
      associated toxicities, a promising approach in the management of infections with
      viruses like cytomegalovirus (CMV), adenovirus (AdV) and EBV is the adoptive
      transfer of T cells targeting these viruses that can be directly isolated from
      the peripheral blood of the donor or expanded ex vivo prior to infusions in
      patients. SUMMARY: T-cell-based immunotherapies are now being included in the
      clinical practice of transplant recipients to prevent and treat infections and
      complications associated with CMV, AdV and EBV. Improvement of current
      limitations will enable the extension of these approaches to all patients at risk
      and to other clinically relevant viruses and pathogens that are emerging as
      significant complications for immunocompromised patients.

PMID- 22614522
TI  - Clostridium difficile:  novel insights on an incessantly challenging disease.
AB  - PURPOSE OF REVIEW: This review comprises recent insights on epidemiology, risk
      factors, diagnostic approaches, pathophysiologic mechanisms, novel treatment
      options and prevention strategies of Clostridium difficile infection (CDI).
      RECENT FINDINGS: Incidence of Clostridium difficile continues to rise and
      hypervirulent subtypes such as polymerase chain reaction (PCR) ribotype 027 and
      078 have emerged worldwide. Children and postpartum women are increasingly
      recognized as being at risk for development of CDI and community-associated
      infection is no longer rare. PCR technology may replace complicated two-step test
      algorithms in the future, because it is rapid, sensitive and specific.
      Pathophysiological studies have provided evidence that either one of the two
      exotoxins A and B is important in conferring virulence - the role of binary toxin
      requires further investigation. Proton pump inhibitors are now established as
      important risk factors for acquiring, complicating CDI, and developing
      recurrences. Fidaxomycin, monoclonal antibodies and intestinal microbiota
      transplantation are promising new treatment options, especially regarding
      prevention of recurrent disease. Future prevention strategies involve vaccination
      and novel insights on reservoirs for ongoing transmission, including the food
      chain. SUMMARY: Important advances in research on CDI include novel diagnostic
      approaches, better understanding of the underlying pathophysiological mechanisms
      of disease and the development of new approaches to treatment.

PMID- 22614523
TI  - Methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci,
      and other Gram-positives in healthcare.
AB  - PURPOSE OF REVIEW: Methicillin-resistant Staphylococcus aureus (MRSA) and
      vancomycin-resistant enterocci (VRE) are the two most common healthcare
      associated multidrug-resistant organisms. The purpose of this article is to
      review recent data regarding the epidemiology, control and treatment of these
      organisms as well as to discuss the emergence of additional antimicrobial
      resistance determinants. RECENT FINDINGS: Although the prevalence of methicillin
      resistance continues to increase among healthcare-associated S. aureus isolates,
      the incidence of invasive MRSA infections appears to be decreasing. Reduced
      susceptibility to vancomycin among MRSA isolates has been associated with
      glycopeptide treatment failure. Resistance to newer antimicrobial agents, such as
      daptomycin and linezolid, has been described among isolates of MRSA and VRE,
      further complicating treatment of infections caused by these organisms. Recent
      studies that have attempted to assess the efficacy of a variety of strategies for
      the prevention of MRSA and/or VRE transmission and infection, including active
      surveillance testing, have been published and additional studies are currently
      underway. SUMMARY: MRSA and VRE remain important causes of morbidity and
      mortality among patients receiving healthcare. The emergence of resistance to
      additional antimicrobial agents highlights the importance of effective prevention
      programs. Further study to determine the optimal approaches to treatment and
      prevention is needed.

PMID- 22614524
TI  - Contralateral pneumothorax in bullous lung after pneumonectomy: report of two
      cases.
AB  - Contralateral pneumothorax after pneumonectomy is potentially fatal. We
      experienced two cases of right pneumothorax after left pneumonectomy in which the
      patients had multiple bullae in the right lung. Case 1 involved a 49-year-old man
      with non-small-cell lung cancer (NSCLC) who underwent left pneumonectomy after
      induction chemoradiotherapy. Eleven months after surgery, he had pneumothorax and
      was treated with chest tube drainage and pleurodesis. He was discharged but died
      of recurrent pneumothorax 1 month later. Case 2 involved a 57-year-old man with
      NSCLC who had left pneumonectomy. Five months after surgery, he had pneumothorax
      and was treated with chest tube drainage. Because of prolonged air leak, ligation
      of the ruptured bulla was performed with a percutaneous cardiopulmonary support
      system on standby. No pneumothorax recurrence occurred for 2 years. Although
      management of pneumothorax after pneumonectomy is challenging, surgical
      intervention may be useful and necessary especially when there is high risk of
      recurrent pneumothorax.

PMID- 22614525
TI  - Resection of the entire first rib for fibrous dysplasia using a combined
      posterior-transmanubrial approach.
AB  - A 27-year-old woman presented with pain of the left anterior chest of 2-year
      duration. Chest X-ray revealed a mass in the upper-left lung field and chest
      computed tomography (CT) a 6-cm first-rib tumor. CT-guided biopsy was performed
      and the tumor diagnosed as fibrous dysplasia. Because of continued pain, surgery
      was deemed necessary. Surgery began with the use of the posterior approach in the
      prone position to expose the first thoracic vertebra and detach the first rib at
      the costotransverse joint. After transitioning to the spine position, the
      transmanubrial approach was used to resect the tumor en bloc with the left first
      rib. Histological examination revealed the tumor to be fibrous dysplasia.
      Postoperative recovery was uneventful. The outcomes of this case suggest that the
      combined posterior-transmanubrial approach described here is a safe, successful
      approach for first-rib resection of a space-occupying tumor that yields good
      cosmetic results.

PMID- 22614526
TI  - One-stage repair with separated cardiopulmonary bypass for coarctation of the
      aorta with left aortic arch and right thoracic descending aorta.
AB  - We treated a 7-day-old neonate with aortic coarctation, left aortic arch, right
      side descending aorta, aberrant right subclavian artery, and outlet ventricular
      septal defect. Surgical one-stage repair consisting of coarctation repair by
      extended direct anastomosis, patch closure of the ventricular septal defect, and
      translocation of the right subclavian artery was performed under a separated
      (upper and lower body) perfusion with ascending and thoracic descending aortic
      cannulation. The postoperative course was complicated with massive chylous
      effusion, which was successfully treated by thoracic duct ligation.

PMID- 22614527
TI  - Stanford type A aortic dissection with intimal intussusception.
AB  - A 51-year-old man presented with acute chest pain and loss of consciousness.
      Computed tomography showed no intimal flap in the ascending aorta and clear
      dissection involving the aortic root and arch, as well as the descending aorta.
      At surgery, the intimal tear was found to be circumferential and dissection
      extended to the proximal aortic arch with intussusception of the intimal layer.
      Emergency graft replacement of the ascending aorta was performed successfully and
      his postoperative course was uneventful.

PMID- 22614528
TI  - Reconstruction of the right ventricular outflow tract after surgical removal of a
      cardiac hemangioma.
AB  - An asymptomatic 73-year-old man underwent resection of a cardiac tumor arising
      from the right ventricular outflow tract, and reconstruction of the right
      ventricular outflow tract using an expanded polytetrafluoroethylene sheet.
      Histological examination revealed a cavernous-capillary type cardiac hemangioma,
      which is a very rare cardiac tumor.

PMID- 22614529
TI  - Harvest technique for pedicled intrathoracic transposition of pectoralis major
      muscle.
AB  - Residual upper pleural spaces after subtotal pulmonary resection continues to
      pose great challenge for the thoracic surgeon. Although not all residual spaces
      deserve surgical attention, only in special situation (empyema with or without
      bronchopleural fistula). It increases morbidity, mortality, hospital stays, and
      costs. Transposition of extrathoracic muscle flaps has been the cornerstone of
      treatment of this complication. Sometimes use of latissimus or serratus muscle
      might have been compromised by the incision for the original operation. In this
      situation the pectoralis major muscle flap (PMF) can be used successfully to
      reach and obliterate upper residual pleural space by anterior approach. The
      technique has never been specifically described before in the literature. We
      describe our technique for mobilization of PMF by anterior approach to obliterate
      residual upper space after major pulmonary resections.

PMID- 22614530
TI  - Non-circumferential tracheal resection with muscle flap reconstruction for
      adenoid cystic carcinoma.
AB  - Circumferential airway resection with primary anastomosis has been widely adopted
      as a treatment for adenoid cystic carcinoma (ACC) of the trachea. However,
      carinal resection is a complicated procedure with high mortality and morbidity
      rates. We describe a technique of non-circumferential tracheal resection
      performed to treat ACC arising from the lower membranous trachea adjacent to the
      carina. The tumor was resected while preserving the tracheo-carinal cartilage. A
      silicone Y-stent was placed at the bifurcation to ensure airway patency before
      closing the defect. The airway defect, measuring 4 * 2.5 cm, was closed using an
      autologous pericardial patch and pedicled latissimus dorsi muscle flap. These
      procedures were technically easy, and no postoperative airway complication
      occurred.

PMID- 22614531
TI  - Targeted therapy vs. DNA-adduct formation-guided design: thoughts about the
      future of metal-based anticancer drugs.
AB  - The development of metal-based anticancer drugs is mainly governed by the
      experience accumulated with cisplatin and its analogues. The synthesis is focused
      on adding appropriate leaving and non-leaving groups to a transition metal in
      order to get more favorable DNA binding properties, and the biological activity
      is tested in vitro, always in a second step, looking for the cell line that is
      killed at the lowest drug concentration. This strategy seems unproductive today
      for the area of new drug development where the knowledge on cancer genomics is
      suggesting the use of targets selectively expressed, or overexpressed by cancer
      cells. These targets almost always are proteins, constituting membrane receptors
      or components of crucial biochemical pathways. Some data indicate that the
      antitumor activity of cisplatin might also be due to the interaction with protein
      targets. This critical review examines the possibilities for metal-based drugs to
      challenge tumors with innovative strategies, based on genomic approaches,
      capitalizing on the chemical experiences with metals in medicine and focusing on
      the nature of the ligands which are added to a metal depending on the selected
      tumor cells and on their molecular targets.

PMID- 22614532
TI  - Functional connectivity and dynamics of cortical-thalamic networks co-cultured in
      a dual compartment device.
AB  - Co-cultures containing dissociated cortical and thalamic cells may provide a
      unique model for understanding the pathophysiology in the respective neuronal sub
      circuitry. In addition, developing an in vitro dissociated co-culture model
      offers the possibility of studying the system without influence from other
      neuronal sub-populations. Here we demonstrate a dual compartment system coupled
      to microelectrode arrays (MEAs) for co-culturing and recording spontaneous
      activities from neuronal sub-populations. Propagation of electrical activities
      between cortical and thalamic regions and their interdependence in connectivity
      is verified by means of a cross-correlation algorithm. We found that burst events
      originate in the cortical region and drive the entire cortical-thalamic network
      bursting behavior while mutually weak thalamic connections play a relevant role
      in sustaining longer burst events in cortical cells. To support these
      experimental findings, a neuronal network model was developed and used to
      investigate the interplay between network dynamics and connectivity in the
      cortical-thalamic system.

PMID- 22614533
TI  - Adenovirus-mediated TRAIL expression and downregulation of Bcl-2 expression
      suppresses non-small cell lung cancer growth in vitro and in vivo.
AB  - Primary or acquired resistance to current treatment methods remains a major
      factor in clinical oncology and may be caused by failures in apoptosis programs.
      TNF-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in several
      human cancer cell types. However, not all cancer cells are susceptible to TRAIL
      and mechanisms of resistance and new strategies to enhance sensitivity are an
      area of intense investigation. Therefore, we investigated whether TRAIL
      resistance is due to Bcl-2 levels. In this study, we generated an adenoviral
      vector, Ad5.TRAIL/siBcl2, that permitted co-expression of shRNA against Bcl-2 and
      the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) therapeutic
      gene from a cytomegalovirus promoter. Infection with Ad5.TRAIL/siBcl2 resulted in
      significant cytotoxicity in non-small cell lung cancer (NSCLC) cells in vitro. In
      contrast, it had no effect on a normal lung cell line, WI-38. Impressively,
      treatment of the established NSCLC tumor model with Ad5.TRAIL/siBcl2 resulted in
      significant tumor regression, compared with other adenoviruses. This potent
      antitumor activity induced by Ad5.TRAIL/siBcl2 was due to strong inhibition of
      Bcl-2 and high expression of TRAIL. Thus, this study may provide a framework for
      future clinical applications of Ad5.TRAIL/siBcl2 in lung tumor gene therapy.

PMID- 22614535
TI  - Motivations and challenges of community-based surveillance volunteers in the
      northern region of Ghana.
AB  - Community health workers (CHWs) are an important element of many health systems
      and programmes for the promotion and delivery of a wide range of health
      interventions and disease surveillance. Understanding the motivation and
      retention of CHWs is recognized as essential but there are few data from sub
      Saharan Africa. This qualitative study explored factors that motivate, and the
      challenges faced by community-based surveillance volunteers (CBSVs) in the
      Northern Region of Ghana through semi-structured interviews with 28 CBSVs, 12
      zonal coordinators, nine Ghana Health Service (GHS) sub-district level staff, ten
      GHS district level staff and two GHS regional level staff in the administrative
      capital. The community emerged as an important motivating factor in terms of
      altruism, a sense of duty to the community and gaining community respect and
      pride. This was enhanced by community selection of the volunteers. Major
      challenges included incorrect community perceptions of CBSVs, problems with
      transportation and equipment, difficulties conducting both volunteer and farm
      work and late or lack of payment for ad hoc tasks such as National Immunization
      Days. Most CBSVs recognized that they were volunteers, understood the constraints
      of the health system and were not demanding remuneration. However, CBSVs strongly
      desired something tangible to show that their work is recognized and appreciated
      and described a number of low cost items that could be used. They also desired
      equipment such as raincoats and identifiers such as tee-shirts and certificates.

PMID- 22614534
TI  - Endothelial protein C receptor expressed by ovarian cancer cells as a possible
      biomarker of cancer onset.
AB  - Coagulation disorders often accompany cancer onset and evolution, which, if not
      properly managed, could have grave consequences. Endothelial protein C is an
      important regulator of homeostasis and acts through its high affinity binding to
      its transmembrane receptor (EPCR). Soluble (sEPCR) which results from the
      proteolytic cleavage of the membrane bound form can trap activated endothelial
      protein C and deprive it of its anti-coagulant function. In this study, the
      expression of EPCR and its soluble form (sEPCR) released into plasma as a result
      of proteolytic cleavage were investigated in ovarian, breast, lung and colorectal
      cancer biopsies, as well as in ascitic cell clusters and peritoneal fluid from
      ovarian cancer samples. In parallel, breast, ovarian, lung and colorectal cancer
      cell lines were investigated for the expression of EPCR. The integrity of the
      EPCR gene sequence as well gene haplotypes were ascertained in the established
      cancer cell lines in order to understand their eventual regulatory functions. The
      results from the present study indicate that in cancer patients, the levels of
      sEPCR are significantly higher than the normal range compared to healthy
      volunteers. The increase in the levels of sEPCR parallels the increase in CA125,
      showing a close correlation. Therefore, the detection of sEPCR in cancer and
      during the post-treatment period could be taken into account as an additional
      marker that could re-inforce the one obtained using CA125 alone as a marker of
      cancer cell mass.

PMID- 22614536
TI  - Attitudes of teenagers towards workplace safety training.
AB  - More than 70 % of teenagers are employed before graduating high school. Every 10
      min, in the United States, a young worker is injured on the job. Safety training
      has been suggested as a way to prevent injuries, yet little is known about the
      methods of safety training and the effectiveness of training that teens receive
      at work. This study is the first to assess the attitudes teens hold towards
      safety training and what they believe would help them stay safe on the job. In
      2010, focus groups and interviews were conducted with 42 teens from public high
      schools in Jefferson County, Kentucky. Participating teens were aged 15-19 years
      old, 43 % male, 69 % African-American, and 56 % worked either in the
      restaurant/food industry or in retail jobs. Most teens reported receiving safety
      training. Although the majority believed that safety training was important, many
      felt that they personally did not need safety training; that it was "common
      sense." However, 52 % of teens reported workplace injuries. Many viewed injury
      lightly and as part of the job, even those that sustained severe injuries. Most
      teens were trained by methods that seem at best "boring" and at worst,
      ineffective. Little interaction, action, or repetition is used. Training is not
      geared towards teens' developmental levels or interest, as in most cases all
      workers received the same type of training. Safety training may be a powerful way
      to reduce injury rates among working teenagers, but it is essential that training
      methods which are geared towards teens are utilized.

PMID- 22614537
TI  - The function of lamins in the context of tissue building and maintenance.
AB  - Lamins are the major structural components of the nuclear lamina found in
      metazoan organisms. Extensive studies using tissue culture cells have shown that
      lamins are involved in a wide range of basic cell functions. This has led to the
      prevailing idea that a given animal cell needs at least one lamin protein for its
      basic proliferation and survival. However, recent studies have shown that lamins
      are dispensable for the proliferation and survival of mouse embryonic stem cells
      (ESC). In contrast to a lack of essential functions in ESCs, certain
      differentiated cells lacking B-type lamins exhibit increased cell cycle exit
      rates and enhanced senescence. In this Extra View, we discuss how studies using
      animal models and cell cultures have begun to reveal cell-type specific functions
      of lamins in tissue building and homeostasis.

PMID- 22614538
TI  - [Infectious diseases in the past and today].

PMID- 22614539
TI  - [The Austrian Red Cross and Austrian bacteriologists in the Balkan wars 1912/13 -
      Centenary of the first application of the bacteriology in theatres of war].
AB  - When Austria joined the Geneva Convention the "Patriotischer Hilfsverein"
      (Patriotic Aid Society) which was founded for the concerns of wounded soldiers,
      was named "Austrian Society of the Red Cross". It had to stand its first big test
      in 1912 in the first Balkan war; military surgeons and bacteriologists were
      deployed to all warring states. The cholera dominated under the infectious
      diseases among the various forces and the civilian populations. Upon request of
      the Bulgarian king renowned bacteriologists of the University of Vienna were
      dispatched. Their work presented the first action of bacteriology for disease
      control on theatres of war. The great success of the surgical and hygienic
      measures initiated in 1912 a reform of the Austrian Red Cross. In 1913 Austria
      made a detailed application to the International Committee of the Red Cross in
      order to extend the Geneva Convention to war epidemics. The Committee forwarded
      and recommended this application to all member states, however, the outbreak of
      the First World War then prevented its resolution.

PMID- 22614540
TI  - ["Hardly a house without ill people" The Spanish Flu in Styria].
AB  - This article examines the impact of the Spanish flu at the microscopic level.
      Main question was if the pandemic killed more people in a selected mountain
      village than the total men of the village who were being killed during the First
      World War. Other topics are the reaction of the local government on the flu and
      which prophylaxis was ordered. The main focus lies on the analysis of the parish
      registers by graphs.

PMID- 22614541
TI  - [Long latency is characteristic for "imported" cases of malaria in children at a
      municipal hospital in Vienna].
AB  - BACKGROUND: Malaria is the most frequent tropical disease and the most important
      parasitic infectious disease in the world. Due to high mobility by travelling and
      migration also in Central Europe malaria has to be considered also in children
      and youths. METHODS: We report four cases of malaria being diagnosed and treated
      at the department of paediatrics, Vienna Danube Hospital, a municipal centre.
      RESULTS: In all cases the latency time or incubation period respectively was long
      with up to one year which made the diagnosis of malaria unlikely at first glance.
      CONCLUSIONS: Taking into account the long latency or incubation period and often
      fragmentary report of medical history malaria has to be considered in all
      children after a stay in a country at risk for malaria even if this stay dates
      back a long time in order to diagnose and treat this disease quickly.

PMID- 22614542
TI  - [Life threatening secondary bacterial infection of varicella skin lesions].
AB  - As immunization coverage of varicella vaccination is low, the disease is still
      very frequent in Austria. Albeit the prognosis in general is good, the incidence
      of varicella-related hospitalization is about 6 per 100,000 in all children
      between 0-15 years of age, affecting mainly previously healthy children.
      Especially young children under the age of 5 are at risk with highest rates among
      children younger than one year. The most common complications are secondary
      bacterial infections, neurological and respiratory complications. Two cases of
      life threatening secondary bacterial infection are presented. One child suffered
      from a Toxic Shock Syndrome caused by group A streptococcus along with large
      necrotizing skin lesions. The second child nearly lost her left eye due to a deep
      orbital abscess. Both children survived without severe sequelae but had to
      undergo several procedures of plastic surgery. Implementation of the varicella
      vaccination program in the USA has shown a near elimination of deaths due to
      severe varicella complications. The initiation of the varicella vaccination
      program for children until the age of 2 in Austria should be considered to
      prevent complications and deaths caused by varicella.

PMID- 22614544
TI  - Smoking found to increase the rate of progression of Barrett esophagus to
      adenocarcinoma.

PMID- 22614545
TI  - Sustained-release bupropion for smoking cessation in a Chinese sample: a double
      blind, placebo-controlled, randomized trial.
AB  - INTRODUCTION: Bupropion is a first-line pharmacological aid for smoking
      cessation; however, no clinical trials have been conducted in a Chinese
      population. METHODS: We enrolled 248 smokers in a hospital-based, randomized,
      smoking cessation trial conducted at four outpatient centers in Beijing. A total
      of 123 participants received an 8-week course of sustained-release bupropion (Bup
      SR) and 125 participants received 8 weeks of placebo. All participants received
      brief education and counseling on smoking cessation. We determined rates of
      abstinence and smoking reduction based on chemical verification and self-report
      at 8 and 12 weeks. RESULTS: At the end of the medication treatment (8 weeks) and
      at the end of the trial (12 weeks), the abstinence rates for Bup-SR were 29.3%
      and 39.8%, respectively, and 10.4% and 8.0% for placebo, respectively (both p <
      .001). Bup-SR was also superior to placebo in reducing cigarettes per day and
      urinary cotinine levels. CONCLUSION: Bup-SR is efficacious for smoking cessation
      in healthy Chinese patients treated in the outpatient setting. It is well
      tolerated with a few mild side effects.

PMID- 22614546
TI  - A longitudinal evaluation of fruit and vegetable consumption and cigarette
      smoking.
AB  - INTRODUCTION: Cross-sectional studies consistently find that cigarette smokers
      consume fewer fruits and vegetables each day than do nonsmokers. However, there
      are no published cohort studies on this relationship. This study evaluated the
      longitudinal relationship between fruit and vegetable consumption (FVC) and
      cigarette smoking, including measures of dependence and abstinence in a national
      population-based cohort analysis. METHODS: A national random-digit-dialed sample
      of 1,000 smokers (aged 25 years and older) assessed baseline FVC and indicators
      of general health orientation. Multivariable analyses were used to assess whether
      baseline FVC was associated with smoking intensity, time to first cigarette
      (TTFC), and total score on an abbreviated version of the Nicotine Dependence
      Syndrome Scale (NDSS), adjusting for age, gender, race/ethnicity, education, and
      household income. The study also assessed whether baseline FVC predicted 30-day
      abstinence from all tobacco products at 14-month follow-up among baseline
      cigarette smokers, with additional adjustment for indicators of general health
      orientation (heavy drinking, exercise, and illicit drug use). RESULTS: Higher FVC
      was associated with fewer cigarettes smoked per day, longer TTFC, and lower NDSS
      score. Those in the highest quartile of FVC were 3.05 times more likely (p < .01)
      than those in the lowest quartile to be abstinent for at least 30 days at follow
      up. CONCLUSIONS: FVC was inversely associated with indicators of nicotine
      dependence and predicted abstinence at follow-up among baseline cigarette
      smokers. Further observational studies and experimental research would provide
      useful information on the consistency of the relationship and help elucidate
      possible mechanisms.

PMID- 22614547
TI  - Pharmacological differences between rat frontal cortex and hippocampus in the
      nicotinic modulation of noradrenaline release implicate distinct receptor
      subtypes.
AB  - INTRODUCTION: Noradrenergic mechanisms in frontal cortex and hippocampus are
      relevant to attentional and stress-related aspects of addiction, respectively.
      Nicotinic receptors (nAChRs) modulate the release of noradrenaline (NA) in these
      tissues. This study determined if similar subtypes of nAChR regulate NA release
      in rat frontal cortex and hippocampus. METHODS: The release of [(3)H]-NA from rat
      tissue prisms was characterized in a 96-well plate assay. In vivo microdialysis
      was used to monitor NA overflow from rat frontal cortex and hippocampus in
      conscious freely moving rats. RESULTS: [(3)H]-NA release from frontal cortex
      prisms was more sensitive to nicotinic agonists than release from hippocampal
      prisms. The beta2-selective agonist 5-iodo-A-85380 was 1000-fold more potent in
      frontal cortex compared with hippocampus. Agonist-evoked [(3)H]-NA release was
      inhibited by the beta2-selective antagonist dihydro-beta-erythroidine (DHbetaE)
      in frontal cortex, whereas in hippocampal tissue, DHbetaE had no effect. In vivo,
      5-iodo-A-85380 (1, 100 MUM) applied locally via the dialysis probe, significantly
      increased NA overflow, compared with basal release, in frontal cortex but not in
      hippocampus. CONCLUSIONS: These data support the modulation of NA release by
      different nAChR subtypes in frontal cortex and hippocampus. The pharmacological
      profile for rat hippocampus is consistent with previous studies, implicating
      alpha3beta4* nAChRs in the modulation of NA release in this tissue. nAChRs having
      this function in frontal cortex are pharmacologically distinct and correspond to
      beta2-containing nAChRs.

PMID- 22614549
TI  - Is routine analysis of pediatric tonsillectomy specimens worth the money?

PMID- 22614550
TI  - Primary acquired cholesteatoma.

PMID- 22614551
TI  - Thyroid hemiagenesis.

PMID- 22614548
TI  - A review of culturally targeted/tailored tobacco prevention and cessation
      interventions for minority adolescents.
AB  - AIM: Emerging racial/ethnic disparities in tobacco use behaviors and resulting
      long-term health outcomes highlight the importance of developing culturally
      tailored/targeted tobacco prevention and cessation interventions. This manuscript
      describes the efficacy and the components of prevention and cessation
      interventions developed for minority adolescents. METHODS: Thirteen studies
      focused on culturally tailoring and targeting tobacco prevention/cessation
      interventions were selected and information on intervention design (type, number
      of sessions), setting (school or community), theoretical constructs, culture
      specific components (surface/deep structures), and treatment outcomes were
      extracted. RESULTS: Of the 13 studies, 5 focused on prevention, 4 on cessation,
      and 4 combined prevention and cessation, and most of the studies were primarily
      school-based, while a few used community locations. Although diverse minority
      groups were targeted, a majority of the studies (n = 6) worked with Hispanic
      adolescents. The most common theoretical construct examined was the Social
      Influence Model (n = 5). The overall findings indicated that culturally tailoring
      cessation interventions did not appear to improve tobacco quit rates among
      minority adolescents, but culturally tailored prevention interventions appeared
      to produce lower tobacco initiation rates among minority adolescents than control
      conditions. CONCLUSIONS: The results of review suggest that there is a critical
      need to develop better interventions to reduce tobacco use among minority
      adolescents and that developing a better understanding of cultural issues related
      to both cessation and initiation of tobacco use among minority populations is a
      key component of this endeavor.

PMID- 22614552
TI  - Diffuse large B-cell lymphoma of the nasopharynx.

PMID- 22614553
TI  - Killian-Jamieson diverticulum.

PMID- 22614554
TI  - Active olfactory training for the treatment of smelling disorders.
AB  - Olfactory function appears to be influenced by repeated odor stimulation. We
      conducted a nonrandomized, nonblinded, retrospective study of the impact of an 8
      month period of olfactory training in patients with olfactory dysfunction. Our
      study population was made up of 46 adults-14 men and 32 women (mean age: 59.17 +/
      13.25 yr)-with olfactory dysfunction of different etiologies (sinonasal: n = 15;
      post-upper-respiratory-tract infection [URTI]: n = 16; post-traumatic: n = 7; and
      idiopathic: n = 8). All patients had been previously treated without success with
      systemic or topical corticosteroids. For their training, patients exposed
      themselves to four different odors twice a day. Olfactory function was evaluated
      at baseline and again at 4 and 8 months, and results were quantified in the form
      of each patient's TDI (threshold, discrimination, and identification) score. Of
      the 46 patients, 28 had undergone olfactory training only, while the remaining 18
      had received topical corticosteroids in addition to training. At study's end, the
      mean overall TDI score in the entire group increased by 4.09 points over baseline
      -a statistically significant increase (p = 0.01); this increase was mainly
      attributable to improvement in the identification component of the TDI, which
      increased by 2.51 points (p = 0.02). Among the 18 patients who received a topical
      corticosteroid in addition to training, the mean TDI increased by 6.83 points (p
      = 0.001), primarily because of improvements in the discrimination and
      identification components. The 28 patients who underwent olfactory training alone
      experienced a mean increase in the identification component of only 2.20 points
      (p = 0.14) after 8 months. Olfactory function in the post-URTI patients increased
      significantly at 4 months. We conclude that olfactory discrimination and
      identification can be enhanced by the addition of a topical corticosteroid to a
      program of defined, daily, short-term exposure to olfactory training.

PMID- 22614555
TI  - Laryngeal schwannoma excised under direct laryngoscopy: case report.
AB  - Laryngeal schwannomas (neurilemmomas) are extremely rare, and they present the
      otorhinolaryngologist with diagnostic and management challenges. These lesions
      usually present as a submucosal mass, and they are always a potential threat to
      the airway. We describe the case of a 75-year-old woman with a laryngeal
      schwannoma that arose from the left postcricoid area and covered the piriform
      sinus and arytenoid cartilage on that side. The tumor was completely excised
      under direct laryngoscopy with the use of a CO(2) laser, and preservation of the
      mucosal lining of the larynx was achieved.

PMID- 22614556
TI  - Primary NK/T-cell lymphoma of the larynx.
AB  - Laryngeal extranodal non-Hodgkin lymphoma is uncommon, accounting for less than
      1% of all laryngeal neoplasms; the B-cell phenotype is predominant. Lymphomas
      outside the nasal cavity are rare and highly aggressive. We present a case of
      primary natural killer T-cell (NK/T-cell) lymphoma of the larynx that arose in a
      45-year-old man. Because only a limited amount of data is available on laryngeal
      NK/T-cell lymphoma, the mainstay of treatment remains unclear, although some data
      suggest that radiotherapy alone is the best option. Our patient was treated with
      chemotherapy and radiotherapy, and he remained in remission 2 years later.

PMID- 22614557
TI  - Bilateral congenital lacrimal fistulae: a case report.
AB  - A congenital lacrimal fistula is a rare developmental anomaly, usually
      unilateral. While it is often asymptomatic, some patients present with epiphora
      or discharge. We report the case of a 4-year-old boy with bilateral lacrimal
      fistulae. No other systemic, nasal, or ocular anomalies were found. In the
      absence of significant symptoms, we decided on a course of observation. In this
      article, we discuss the embryologic basis of congenital lacrimal fistulae, as
      well as the typical presentation and possible treatment modalities. The presence
      of a lacrimal fistula is an indication to search for a variety of underlying
      systemic and ocular anomalies.

PMID- 22614558
TI  - Primary intraosseous cavernous hemangioma of the zygoma: a case report and
      literature review.
AB  - Intraosseous hemangiomas are rare. We report the case of a 47-year-old man who
      presented with a gradually enlarging left zygomatic mass that had caused pain,
      deformity, and superficial soft-tissue swelling. Computed tomography revealed a
      well-circumscribed 2.0 * 2.5-cm mass with a ground-glass matrix in the left
      zygoma. Following surgical excision, the patient's symptoms resolved. Findings on
      pathologic examination of the excised tissue were consistent with an intraosseous
      cavernous hemangioma. We describe the features of this rare case, we discuss the
      pertinent radiologic features and pathophysiology of intraosseous hemangiomas,
      and we review the available literature.

PMID- 22614559
TI  - Inflammatory myofibroblastic tumor of the nose and paranasal sinuses masquerading
      as a malignancy.
AB  - Inflammatory myofibroblastic tumor (IMT) of the nose and paranasal sinuses is a
      rare entity that exhibits a diverse histologic pattern that can mimic malignant
      tumors clinically and radiologically. We present a case of IMT in an 88-year-old
      man who presented with an aggressive tumor-like lesion in the nose and paranasal
      sinuses that had a malignant appearance on radiology. We discuss this tumor's
      clinicoradiologic resemblance to a malignancy, and we review the treatment
      options following careful histologic and immunohistochemical analysis.

PMID- 22614560
TI  - Lymphangiomatous polyp of the nasal cavity: a rare presentation.
AB  - Lymphangiomatous polyp of the nasal cavity is a very rare condition. We are
      reporting a case of a unilateral nasal mass presenting with noisy breathing
      during sleep, change of voice, watery nasal discharge, and anosmia in a 5-year
      old boy. The mass was removed via a transnasal endoscopic approach, and a
      diagnosis of lymphangiomatous nasal polyp was established by histopathology.

PMID- 22614561
TI  - Giant tracheocele with multiple congenital anomalies.
AB  - Tracheocele--an outpouching of tracheal mucous membrane--is an uncommon entity.
      It can occur as a congenital or acquired form. The congenital entity remains
      mostly dormant until adulthood, and then it typically presents as a herniation
      with multiple air-filled sacs. The acquired form develops as the result of blunt
      trauma, recurrent pulmonary infection, intubation, instrumentation, or surgery,
      and it typically presents as a single paratracheal cavity. We present an
      extremely rare case of a tracheocele associated with multiple congenital
      anomalies involving the face, limbs, and heart.

PMID- 22614562
TI  - A concha bullosa mucopyocele manifesting as migraine headaches: a case report and
      literature review.
AB  - A concha bullosa is a common anatomic variant that represents an aerated
      turbinate, usually the middle turbinate. It is usually asymptomatic. When
      extensively pneumatized, a large concha bullosa may cause significant problems,
      including headache, nasal obstruction, and blockage of sinus drainage. We report
      a case of a large concha bullosa mucopyocele that manifested as recurring
      migraine headaches. It was successfully treated with surgical excision. We also
      review the available literature.

PMID- 22614563
TI  - Osteoid osteoma of the ethmoid sinus: a rare diagnosis.
AB  - Osteoid osteomas are benign osseous lesions. They have seldom been described in
      the otolaryngology literature, and they are extremely rare in the ethmoid
      sinuses. We report a new case of osteoid osteoma of the ethmoid sinus in a 15
      year-old girl. The workup consisted of computed tomography. Treatment involved
      local excision via an external ethmoidectomy approach. The diagnosis was based on
      histopathologic examination.

PMID- 22614564
TI  - Laryngeal papilloma.

PMID- 22614565
TI  - Endoscopic view of an asymmetric roof of the ethmoid sinus.

PMID- 22614566
TI  - Mycobacterial tuberculosis superimposed on a Warthin tumor.
AB  - The concomitant occurrence of tuberculosis infection within a Warthin tumor is
      extremely rare, as only 6 cases have been previously reported in the English
      language literature. We report a new case in a 92-year-old man, who presented
      with a 20-year history of a painless swelling in the right infra-auricular area
      that had recently become painful and larger. The patient had no history of
      tuberculosis, weight loss, or chronic cough. The fluctuant mass was aspirated,
      but histopathology and routine culture were negative. Computed tomography
      identified a 5-cm, heterogeneous, enhancing mass with multiple, variably sized,
      low-density areas without surrounding edema in the area of the right parotid
      gland. Complete excision was performed to relieve the patient's symptoms.
      Histopathology diagnosed an acid-fast bacillus infection within a Warthin tumor.
      On polymerase chain reaction testing, formalin-fixed, paraffin-embedded tissue
      was negative for tuberculosis, but subsequent culture identified Mycobacterium
      tuberculosis. Initially, the patient refused antituberculosis therapy, but he
      relented when miliary pulmonary tuberculosis was diagnosed 11 weeks
      postoperatively.

PMID- 22614567
TI  - Aneurysmal bone cyst at the base of the skull.
AB  - Aneurysmal bone cysts have been described as pseudocysts in view of their lack of
      an epithelial lining. These cysts are uncommon, but when they do occur they
      typically involve the long bones of the extremities, the membranous bones of the
      thorax and pelvis, and the vertebrae. Skull involvement is uncommon. We present
      the case of a 14-year-old girl who presented with nasal obstruction and a
      swelling of the right cheek. Contrast-enhanced computed tomography detected a
      heterogeneous cystic mass involving the sphenoid and ethmoid bones. The mass was
      excised via a lateral rhinotomy approach, and it was identified as an aneurysmal
      bone cyst on histologic examination. The patient experienced a recurrence in the
      right sphenoid sinus within 3 months, and the lesion was removed via transnasal
      endoscopy.

PMID- 22614568
TI  - Induction of DNA double-strand breaks by monochlorophenol isomers and ChKM in
      human gingival fibroblasts.
AB  - Phenol has been traditionally used in dental treatment as a sedative for the pulp
      or as disinfectant for carious cavity and root canal. However, phenol is regarded
      as a mutagenic and carcinogenic agent and its use in dental practice is now
      therefore restricted. Monochlorophenols are derivatives of phenol, which are
      still used clinically as root canal disinfectants, they are even more active
      antiseptics/disinfectants than phenol, and the so-called Walkhoff (ChKM) solution
      makes use of monochlorophenol for root canal disinfection. Ingredients in the
      ChKM solution are the monochlorophenol compound 4-chlorophenol (4-CP), camphor,
      and menthol. In literature, the use of the ChKM solution is controversial because
      of a possible DNA toxicity of the ingredient 4-CP. However, it is unknown whether
      ChKM can really induce DNA damage in human oral cells. In this study, the
      induction of DNA double-strand breaks (DSBs) by ChKM and monochlorophenol
      compounds (2-chlorophenol, 2-CP; 3-chlorophenol, 3-CP; and 4-chlorophenol, 4-CP)
      was tested in human gingival fibroblasts (HGFs). DNA DSBs (foci) induced in HGFs
      unexposed and exposed to monochlorophenols or ChKM solution were investigated
      using the gamma-H2AX DNA focus assay, which is a direct marker for DSBs. DSBs
      result in the ATM-dependent phosphorylation of the histone H2AX. When cells were
      exposed to medium or medium + DMSO (1 %) (negative controls), an average of 3
      foci per cell were found. In positive control cells (H2O2 + medium, or H2O2 +
      medium + DMSO (1 %), an average of 35 foci each were found. About 20 DSB foci per
      cell were found, when HGFs were exposed to 2-CP (4 mM), 3-CP (2.3 mM), 4-CP (2.1
      mM), or ChKM (corresponding to 1.5 mM 4-CP). Our results show increasing DNA
      toxicities in the order of 2-CP < 3-CP < 4-CP < ChKM solution. An additive DNA
      toxicity was found for 4-CP in combination with camphor in the ChKM solution,
      compared to the 4-CP alone. No significant differences regarding multi-foci cells
      (cells that contain more than 40 foci) were found when HGFs were exposed to the
      EC50 concentrations (given in parenthesis) of ChKM (1.5 mM), 4-CP (2.1 mM), or 2
      CP (4 mM). Significantly fewer multi-foci cells were found when HGFs were exposed
      to the EC50 concentration (given in parenthesis) of 3-CP (2.3 mM), compared to
      the EC50 concentrations of ChKM, 4-CP, or 2-CP. Monochlorophenol compounds and/or
      ChKM solution can induce DSBs in primary human oral (cavity) cells, which
      underscores their genotoxic capacity.

PMID- 22614569
TI  - Synthesis of an unusual dinuclear chiral iron complex and its application in
      asymmetric hydrophosphorylation of aldehydes.
AB  - An unusual dinuclear chiral iron complex has been synthesized and effectively
      utilized in the asymmetric hydrophosphorylation of aldehydes to synthesize
      optically active alpha-hydroxy phosphonates with excellent yield and good
      enantioselectivity.

PMID- 22614571
TI  - Creutzfeldt-Jakob disease revealed by a logopenic variant of primary progressive
      aphasia.
AB  - Logopenic aphasia, mainly characterized by word anomia, sentence and phrase
      comprehension difficulties secondary to phonological loop deficits but relatively
      preserved single word comprehension and no agrammatism, is one of the 3 main
      variants of primary progressive aphasia (PPA). We describe the first case of PPA
      that fulfilled clinical criteria of logopenic aphasia but showed abnormal DWI
      hyperintensities that were predominant on the left hemisphere and compatible with
      Creutzfeldt-Jakob disease (CJD). After abnormally long isolated language
      deficits, the patient rapidly worsened and died. Autopsy performed 18 months
      after onset of language difficulties confirmed the diagnosis. We therefore
      advocate performing DWI sequences in any suspicion of PPA in order to rule out
      CJD.

PMID- 22614570
TI  - Impact of resident duty hour limits on safety in the intensive care unit: a
      national survey of pediatric and neonatal intensivists.
AB  - OBJECTIVE: Resident duty-hour regulations potentially shift the workload from
      resident to attending physicians. We sought to understand how current or future
      regulatory changes might impact safety in academic pediatric and neonatal
      intensive care units. DESIGN: Web-based survey. SETTING: U.S. academic pediatric
      and neonatal intensive care units. SUBJECTS: Attending pediatric and neonatal
      intensivists. INTERVENTIONS: We evaluated perceptions on four intensive care unit
      safety-related risk measures potentially affected by current duty-hour
      regulations: 1) attending physician and resident fatigue; 2) attending physician
      workload; 3) errors (self-reported rates by attending physicians or perceived
      resident error rates); and 4) safety culture. We also evaluated perceptions of
      how these risks would change with further duty-hour restrictions. MEASUREMENTS
      AND MAIN RESULTS: We administered our survey between February and April 2010 to
      688 eligible physicians, of whom 360 (52.3%) responded. Most believed that
      resident error rates were unchanged or worse (91.9%) and safety culture was
      unchanged or worse (84.4%) with current duty-hour regulations. Of respondents,
      61.9% believed their own work-hours providing direct patient care increased and
      55.8% believed they were more fatigued while providing direct patient care. Most
      (85.3%) perceived no increase in their own error rates currently, but in the
      scenario of further reduction in resident duty-hours, over half (53.3%) believed
      that safety culture would worsen and a significant proportion (40.3%) believed
      that their own error rates would increase. CONCLUSIONS: Pediatric intensivists do
      not perceive improved patient safety from current resident duty-hour
      restrictions. Policies to further restrict resident duty-hours should consider
      unintended consequences of worsening certain aspects of intensive care unit
      safety.

PMID- 22614572
TI  - Microwave accelerated Glaser-Hay macrocyclizations at high concentrations.
AB  - Efficient macrocyclization can be conducted at high concentrations employing
      microwave irradiation and a phase separation strategy. The rate of the Glaser-Hay
      macrocyclization is accelerated using microwave irradiation and reaction times
      decreased from 48 h to 1-6 h, depending on the nature of the substrate.
      Macrocyclization concentrations could be increased up to 0.1 M compared to
      traditional concentrations (0.2 mM).

PMID- 22614573
TI  - Image change detection using paradoxical theory for patient follow-up
      quantitation and therapy assessment.
AB  - In clinical oncology, positron emission tomography (PET) imaging can be used to
      assess therapeutic response by quantifying the evolution of semi-quantitative
      values such as standardized uptake value, early during treatment or after
      treatment. Current guidelines do not include metabolically active tumor volume
      (MATV) measurements and derived parameters such as total lesion glycolysis (TLG)
      to characterize the response to the treatment. To achieve automatic MATV
      variation estimation during treatment, we propose an approach based on the change
      detection principle using the recent paradoxical theory, which models
      imprecision, uncertainty, and conflict between sources. It was applied here
      simultaneously to pre- and post-treatment PET scans. The proposed method was
      applied to both simulated and clinical datasets, and its performance was compared
      to adaptive thresholding applied separately on pre- and post-treatment PET scans.
      On simulated datasets, the adaptive threshold was associated with significantly
      higher classification errors than the developed approach. On clinical datasets,
      the proposed method led to results more consistent with the known partial
      responder status of these patients. The method requires accurate rigid
      registration of both scans which can be obtained only in specific body regions
      and does not explicitly model uptake heterogeneity. In further investigations,
      the change detection of intra-MATV tracer uptake heterogeneity will be developed
      by incorporating textural features into the proposed approach.

PMID- 22614574
TI  - Model-based tomographic reconstruction of objects containing known components.
AB  - The likelihood of finding manufactured components (surgical tools, implants,
      etc.) within a tomographic field-of-view has been steadily increasing. One reason
      is the aging population and proliferation of prosthetic devices, such that more
      people undergoing diagnostic imaging have existing implants, particularly hip and
      knee implants. Another reason is that use of intraoperative imaging (e.g., cone
      beam CT) for surgical guidance is increasing, wherein surgical tools and devices
      such as screws and plates are placed within or near to the target anatomy. When
      these components contain metal, the reconstructed volumes are likely to contain
      severe artifacts that adversely affect the image quality in tissues both near and
      far from the component. Because physical models of such components exist, there
      is a unique opportunity to integrate this knowledge into the reconstruction
      algorithm to reduce these artifacts. We present a model-based penalized
      likelihood estimation approach that explicitly incorporates known information
      about component geometry and composition. The approach uses an alternating
      maximization method that jointly estimates the anatomy and the position and pose
      of each of the known components. We demonstrate that the proposed method can
      produce nearly artifact-free images even near the boundary of a metal implant in
      simulated vertebral pedicle screw reconstructions and even under conditions of
      substantial photon starvation. The simultaneous estimation of device pose also
      provides quantitative information on device placement that could be valuable to
      quality assurance and verification of treatment delivery.

PMID- 22614575
TI  - Onychopathy induced by temsirolimus, a mammalian target of rapamycin inhibitor.
AB  - Temsirolimus belongs to the mammalian target of rapamycin (mTOR) inhibitors,
      targeted therapies for which indications are booming in oncology. While their
      tolerance is usually good, mucocutaneous toxicity is the most common, including
      stomatitis, rashes, edemas, pruritus, dry skin and nail disorders. The latter are
      common in clinical practice but have not yet been well characterized. We report 2
      cases of patients who developed, after 6-7 months with temsirolimus, a dystrophy
      of the 20 nails with fragility, distal onycholysis, yellow discoloration,
      associated in 1 case with painful paronychia. Topical steroids improved the
      paronychia, without changing the nail dystrophy. To our knowledge, the occurrence
      of yellow nail discoloration with temsirolimus has never been reported before. We
      review the cutaneous and mucosal toxicities induced by temsirolimus and
      everolimus, two mTOR inhibitors used as anticancer agents and by their parent
      molecule sirolimus.

PMID- 22614576
TI  - Developing an interactive web-based learning program on skin cancer: the learning
      experiences of clinical educators.
AB  - Web-based learning in medical education is rapidly growing. However, there are
      few firsthand accounts on the rationale for and development of web-based learning
      programs. We present the experience of clinical educators who developed an
      interactive online skin cancer detection and management course in a time
      efficient and cost-efficient manner without any prior skills in computer
      programming or technical construction of web-based learning programs. We review
      the current state of web-based learning including its general advantages and
      disadvantages as well as its specific utility in dermatology. We then detail our
      experience in developing an interactive online skin cancer curriculum for primary
      care clinicians. Finally, we describe the main challenges faced and lessons
      learned during the process. This report may serve medical educators who possess
      minimal computer programming and web design skills but want to employ the many
      strengths of web-based learning without the huge costs associated with hiring a
      professional development team.

PMID- 22614578
TI  - Direct airborne acoustic wave modulation of Fabry-Perot fiber laser (FPFL) over
      100 kHz of operating bandwidth.
AB  - The idea of applying a simple Fabry-Perot fiber laser (FPFL) set-up in a free
      running condition as an acoustic sensing medium is proposed. Conventional optical
      microphone requires a stringently aligned diaphragm to mediate the acoustic
      impedance mismatch between air and silica fiber. Motivated by the difficulty of
      optical sensing of airborne acoustic waves, a new sensing method is proposed to
      sense acoustic waves without the assistance of a diaphragm as transducer. By
      studying the output power fluctuation of the FPFL, the operating bandwidth and
      sensitivity of the proposed sensing method are determined. The tunability of the
      resonant frequency from 5 kHz to 85 kHz allows sensing of acoustic waves in the
      range of 100 Hz to 100 kHz. Tuning of the resonant frequency can be performed by
      changing the optical pumping power from as low as 10 mW to 68.5 mW or higher.

PMID- 22614579
TI  - Design of mode-sorting asymmetric Y-junctions.
AB  - The theory of mode-sorting in bimodal asymmetric Y-junctions is extended to
      multimode asymmetric Y-junctions with multiple output arms. This theory allows
      for the optimization of these mode-sorting planar structures. Asymmetric Y
      junctions provide unique opportunities for spatial mode division multiplexing
      (MDM) of optical fiber. Spatial MDM is considered paramount to overcoming the
      bandwidth limitations of single-mode fiber. The design criteria presented in this
      paper facilitate their design.

PMID- 22614580
TI  - T- and Y-splitters based on an Au/SiO2 nanoring chain at an optical communication
      band.
AB  - In this paper, we have utilized Au nanoring chains in an SiO2 host to design
      certain T-and Y-structures, and expanded it to transport and split the
      electromagnetic energy in integrated nanophotonic devices operating at an optical
      communication band (lambda~1550 nm). We compared two structures and tried to
      choose the best one, with lower losses and higher efficiency at the output
      branches, in order to split and transport the optical energy. Comparing the
      different types of nanoparticles corroborates that nanorings have an extra degree
      of tunability in their geometrical components. Meanwhile, nanorings show strong
      confinement in near-field coupling, less extinction coefficient, and also lower
      scattering into the far field during energy transportation at the C-band
      spectrum. Due to the nanoring's particular properties, transportation losses
      would be lower than in other nanoparticle-based structures like nanospheres,
      nanorods, and nanodisks. We demonstrate that Au nanorings surrounded by an SiO2
      host yield suitable conditions to excite surface Plasmons inside the metal.
      Comparison between Y-and T-splitters shows that the Y-splitter is a more suitable
      alternative than the T-splitter, with higher transmission efficiency and lower
      losses. In the Y-structure, the power ratio (time-averaged power across the
      surface) is 24.7%, and electromagnetic energy transportation takes place at group
      velocities in the vicinity of 30% of the velocity of light; transmission losses
      are gammaT=3 dB/655 nm and gammaT=3 dB/443 nm. In this work, we have applied the
      finite-difference time-domain method (FDTD) to simulate and indicate the
      properties of structures.

PMID- 22614581
TI  - Stand-off detection of solid targets with diffuse reflection spectroscopy using a
      high-power mid-infrared supercontinuum source.
AB  - We measure the diffuse reflection spectrum of solid samples such as explosives
      (TNT, RDX, PETN), fertilizers (ammonium nitrate, urea), and paints (automotive
      and military grade) at a stand-off distance of 5 m using a mid-infrared
      supercontinuum light source with 3.9 W average output power. The output spectrum
      extends from 750-4300 nm, and it is generated by nonlinear spectral broadening in
      a 9 m long fluoride fiber pumped by high peak power pulses from a dual-stage
      erbium-ytterbium fiber amplifier operating at 1543 nm. The samples are
      distinguished using unique spectral signatures that are attributed to the
      molecular vibrations of the constituents. Signal-to-noise ratio (SNR)
      calculations demonstrate the feasibility of increasing the stand-off distance
      from 5 to ~150 m, with a corresponding drop in SNR from 28 to 10 dB.

PMID- 22614582
TI  - Adaptive semianalytical inversion of ocean color radiometry in optically complex
      waters.
AB  - To address the challenges of the parameterization of ocean color inversion
      algorithms in optically complex waters, we present an adaptive implementation of
      the linear matrix inversion method (LMI) [J. Geophys. Res.101, 16631 (1996)],
      which iterates over a limited number of model parameter sets to account for
      naturally occurring spatial or temporal variability in inherent optical
      properties (IOPs) and concentration specific IOPs (SIOPs). LMI was applied to a
      simulated reflectance dataset for spectral bands representing measured water
      properties of a macrotidal embayment characterized by a large variability in the
      shape and amplitude factors controlling the IOP spectra. We compare the inversion
      results for the single-model parameter implementation to the adaptive
      parameterization of LMI for the retrieval of bulk IOPs, the IOPs apportioned to
      the optically active constituents, and the concentrations of the optically active
      constituents. We found that ocean color inversion with LMI is significantly
      sensitive to the a priori selection of the empirical parameters g0 and g1 of the
      equations relating the above-surface remote-sensing reflectance to the IOPs in
      the water column [J. Geophys. Res.93, 10909 (1988)]. When assuming the values
      proposed for open-ocean applications for g0 and g1 [J. Geophys. Res.93, 10909
      (1988)], the accuracy of the retrieved IOPs, and concentrations was substantially
      lower than that retrieved with the parameterization developed for coastal waters
      [Appl. Opt.38, 3831 (1999)] because the optically complex waters analyzed in this
      study were dominated by particulate and dissolved matter. The adaptive
      parameterization of LMI yielded consistently more accurate inversion results than
      the single fixed SIOP model parameterizations of LMI. The adaptive implementation
      of LMI led to an improvement in the accuracy of apportioned IOPs and
      concentrations, particularly for the phytoplankton-related quantities. The
      adaptive parameterization encompassing wider IOP ranges were more accurate for
      the retrieval of bulk IOPs, apportioned IOPs, and concentration of optically
      active constituents.

PMID- 22614583
TI  - Demonstration of a simplified optical mouse lighting module by integrating the
      non-Lambertian LED chip and the free-form surface.
AB  - A cost-effective, high-throughput, and high-yield method for the efficiency
      enhancement of an optical mouse lighting module is proposed. We integrated
      imprinting technology and free-form surface design to obtain a lighting module
      with high illumination efficiency and uniform intensity distribution. The
      imprinting technique can increase the light extraction efficiency and modulate
      the intensity distribution of light-emitting diodes. A modulated light source was
      utilized to add a compact free-form surface element to create a lighting module
      with 95% uniformity and 80% optical efficiency.

PMID- 22614584
TI  - Use of attenuated total reflectance Fourier transform infrared spectroscopy to
      monitor the development of lipid aggregate structures.
AB  - Attenuated total reflectance Fourier transform infrared spectroscopy is used to
      monitor the adsorption of 100 nm 1,2-dipalmitoyl-sn-glycero-3-phosphocholine
      (DPPC) phospholipid vesicles to the surfaces of Ge, electrolessly deposited Au,
      and a well formed self-assembled monolayer of 1-octadecanethiol. The interaction
      of DPPC vesicles in solution with these different surfaces yields distinctly
      different surface structures: intact DPPC vesicles on Ge, a supported
      phospholipid bilayer on an electrolessly deposited Au surface, and a phospholipid
      monolayer onto the hydrophobic self-assembled monolayer. IR peak position,
      bandwidth, and intensity are used to confirm structure formation and quantitation
      of the amount of lipid that desorbs during film formation.

PMID- 22614585
TI  - Shift-multiplexed microhologram fabrication with photoisomeric chromophores.
AB  - Microholographic memory is an attractive storage system for its capability to
      hold high-density data and for its access time. Using a photochromic chromophore
      (diarylethene)-doped recording medium can give rise to microholographic memory's
      durability and contrast. In addition, it is possible to increase the
      microholographic memory's density by shift-multiplexed recording, since a
      hologram pit is constructed in a small area. The microhologram was fabricated in
      the diarylethene-based sample with two counterpropagating focused beams. Also,
      surface images and cross-sectional images scanned by a confocal microscope
      indicated that shift-multiplexed recording was achieved in high contrast.

PMID- 22614586
TI  - Resonator fiber optic gyro employing a semiconductor laser.
AB  - Resonator fiber optic gyro (RFOG) based on the Sagnac effect has the potential to
      achieve the inertial navigation system requirement with a short sensing coil.
      Semiconductor laser is one of the key elements for integration and
      miniaturization of the RFOG. In this paper, an RFOG employing a semiconductor
      laser is demonstrated. The model of the laser frequency noise induced error in
      the RFOG is described. To attenuate the laser frequency noise induced error,
      active frequency stabilization is applied. An online laser frequency noise
      observation is built, as a powerful optimum criterion for the loop parameters.
      Moreover, the laser frequency noise observation method is developed as a new
      measurement tool. With a fast digital proportional integrator based on a single
      field programmable gate array applied in the active stabilization loop, the laser
      frequency noise is reduced to 0.021 Hz (1sigma). It is equivalent to a rotation
      rate of 0.07 degrees /h, and close to the shot noise limit for the RFOG. As a
      result, a bias stability of open-loop gyro output is 9.5 degrees /h (1sigma) for
      the integration time 10 s in an hour observed in the RFOG. To the best of our
      knowledge, this result is the best long-term stability using the miniature
      semiconductor laser.

PMID- 22614587
TI  - Influence of ion assistance on LaF3 films deposited by molybdenum boat
      evaporation.
AB  - LaF3 thin films at 193 nm were deposited by the molybdenum boat evaporation with
      ion-assisted deposition (IAD). Various optical characteristics, stress, and
      microstructures that formed under different ion-beam voltages of IAD deposition
      were investigated. The relation between these properties is also discussed. LaF3
      films deposited with IAD exhibited small rough surfaces and large optical loss at
      193 nm. The largest value of optical loss for films at 193 nm, which were
      prepared at an ion-beam voltage of 400 V, was 1.55% and the extinction
      coefficient was smaller than 0.0015. Microstructures and crystalline structures
      of films were influenced and changed by the ion-assisted deposition process.
      Tensile stress value of films increased as the ion-beam voltage rose. Refractive
      index, related to the packing density and microstructures, also increased as the
      ion-beam voltage rose.

PMID- 22614588
TI  - Quadratic electro-optic properties of Pb(Mg1/3Nb2/3)O3-PbTiO3 transparent
      ceramics under both DC and AC bias.
AB  - The basic quadratic electro-optic properties of Pb(Mg1/3Nb2/3)O3-PbTiO3 (PMN-PT)
      transparent ceramics have been studied under both DC and AC electric field bias.
      The contribution of piezoelectric resonance to electro-optic effect for this
      quadratic electro-optic ceramics material has been experimentally demonstrated
      and theoretically analyzed. It is found that, at the piezoelectric resonance
      frequencies, the piezoelectric induced electro-optic effect dominates and leads
      to a dramatically high sensitivity for weak electric signal detection. About 20
      dB signal-to-noise ratio is attained when detecting AC electric field strength of
      1 V/m with optimized DC bias. Besides, the effects of AC frequency and amplitude
      on halfwave voltage V(pi) of PMN-PT are investigated.

PMID- 22614589
TI  - Interpixel crosstalk in Teledyne Imaging Sensors H4RG-10 detectors.
AB  - Complementary metal-oxide semiconductor (CMOS)-hybrid arrays have become
      competitive optical detectors for use in ground- and space-based astronomy.
      Interpixel capacitance (IPC) is one source of error that appears in most CMOS
      arrays. In this paper, we use a single-pixel-reset method to model IPC. We
      combine this IPC model with a model for charge diffusion to estimate the total
      crosstalk on H4RG-10 arrays. Finally, we compare our model results to 55Fe data
      obtained using an astrometric camera built to test the H4RG-10 B0 generation
      detectors.

PMID- 22614590
TI  - Scintillation correlation between forward and return spherical waves.
AB  - According to the point-source point-receiver (PSPR) reciprocity, the received
      field remains equal when the positions of a point source and point receiver are
      interchanged. We extend the PSPR scenario to a finite receiver that spatially
      averages scintillation over its aperture. By use of weak-fluctuation theory, an
      analytical expression for the correlation coefficient between the received powers
      at both link ends is provided. The effects of turbulence profile, receiver
      aperture size, and central obscuration on the correlation are assessed. Because
      correlation is obtained to the detriment of antenna gain and aperture averaging,
      the net benefit of the channel reciprocity is highly scenario dependent.

PMID- 22614591
TI  - Detailed analysis of a 40 GHz all-optical synchronization based on an amplified
      feedback distributed feedback laser.
AB  - We demonstrate an all-optical synchronization using an amplified-feedback
      distributed feedback laser with coherent injection experimentally, which can
      synchronize 40 GHz degraded signals even with optical signal-to-noise ratio as
      low as 5 dB, or chromatic dispersion as large as 408 ps/nm. Besides, this optical
      synchronization has a large range of power operation, i.e. high sensitivity of
      synchronization, from -21.40 dBm to -8.23 dBm, as well as a large frequency
      locking range of 190 MHz.

PMID- 22614592
TI  - Observation of the Gouy phase anomaly in astigmatic beams.
AB  - The Gouy phase anomaly, well established for stigmatic beams, is validated here
      for astigmatic beams. We simulate the predicted Gouy phase anomaly near
      astigmatic foci using a beam propagation algorithm integrated within lens design
      software. We then compare computational results with experimental data acquired
      using a modified Mertz-Sagnac interferometer. Both in simulation and in
      experiment, results show that a pi/2-phase change occurs as the beam passes
      through each of the astigmatic foci, experimentally validating results derived in
      a recent paper by Visser and Wolf [Opt. Commun. 283, 3371-3375 (2010)].

PMID- 22614593
TI  - Tuned switching of surface waves by a liquid crystal cap layer in one-dimensional
      photonic crystals.
AB  - In this paper, we theoretically study the electromagnetic surface waves localized
      at the interface between a homogeneous dielectric medium and a semi-infinite, one
      dimensional photonic crystal (1D PC). The semi-infinite 1D PC is made of
      alternative layers of right-handed (RH) and dispersive left-handed (LH) materials
      in the presence of a liquid crystal (LC) cap layer. In this structure, we derive
      the surface waves dispersion relation with tunable switching and localization by
      using an analytical direct matching procedure within the Kronig-Penny model. It
      is shown that, for both of layer arrangements, the variation of molecules
      orientation of the LC cap layer acts as an effective tool to tune the type (tuned
      switching) and localization of the surface waves and it also can create a surface
      mode with maximum localization in the first frequency bandgap.

PMID- 22614594
TI  - Optimized half-wave voltage and insertion loss in a strip-loaded waveguide
      electro-optic polymer modulator.
AB  - A strip-loaded waveguide, electro-optic modulator was designed and analyzed in
      terms of single mode conditions, optical loss due to the metal electrodes,
      modulation efficiency, and mode size. Two designs were compared: Design 1
      optimized the half-wave voltage (V(pi)=1.1 V) with a nearly symmetric waveguide
      by maximizing modulation efficiency and minimizing the overall thickness of the
      waveguide; Design 2 optimized the insertion loss by reducing coupling loss by 4.6
      dB via a strongly asymmetric waveguide that maximizes the overall mode size to
      most efficiently overlap with a single mode fiber. Design 2 also has a favorable
      half-wave voltage (V(pi)=1.75 V). Some general guidelines in the selection of
      cladding layers in a detailed design of a poled-polymer electro-optic modulator
      incorporating a strip-loaded waveguide structure are suggested.

PMID- 22614595
TI  - Poincare-beam patterns produced by nonseparable superpositions of Laguerre-Gauss
      and polarization modes of light.
AB  - We present a study of Poincare-beam polarization patterns produced by collinear
      superposition of two Laguerre-Gauss spatial modes in orthogonal polarization
      eigenstates (circular or linear). We explore theoretically and experimentally the
      combinations that are possible. We find that the resulting patterns can be
      explained in terms of mappings of points on the Poincare sphere onto points in
      the transverse plane of the beam mode. The modes that we produced yielded many
      types of polarization singularities.

PMID- 22614596
TI  - Chaotic ultra-wideband radio generator based on an optoelectronic oscillator with
      a built-in microwave photonic filter.
AB  - We induce a microwave photonic bandpass filter into an optoelectronic oscillator
      to generate a chaotic ultra-wideband signal in both the optical and electrical
      domain. The theoretical analysis and numerical simulation indicate that this
      system is capable of generating band-limited high-dimensional chaos. Experimental
      results coincide well with the theoretical prediction and show that the power
      spectrum of the generated chaotic signal basically meets the Federal
      Communications Commission indoor mask. The generated chaotic carrier is further
      intensity modulated by a 10 MHz square wave, and the waveform of the output ultra
      wideband signal is measured for demonstrating the chaotic on-off keying
      modulation.

PMID- 22614597
TI  - Phase control requirements of high intensity laser beam combining.
AB  - Aiming at getting the general requirements of the beam combine for ignition scale
      laser facilities, the analytical expressions including the factors affecting the
      combine results are derived. The physical meanings of every part are illustrated.
      Based on these expressions, the effects of the factors, including the beam
      configuration, piston error, and tip/tilt error, are studied analytically and
      numerically. The results show that the beam configuration cannot affect the
      Strehl ratio (SR) of the combined beam, but it influences the FWHM of the main
      peak and the ratio of the main peak and the side peak. The beam separation should
      be no more than 1.24 times the individual beam width for the multibeam combine,
      and be close to the individual beam width for the two-beam combine as much as
      possible. The piston error can change the characteristics of the combine beam
      focus, including the peak intensity, the focal spot morphology, the fractional
      energy contained within a certain area, and the center of mass. For the two-beam
      combine, a piston error less than 2pi/5 rad is suitable, and for the multibeam
      combine, the standard deviation of the piston error should be no more than 2pi/10
      rad. The tip/tilt error has a great influence on the combined results. It affects
      the superposition degree of the focal spots of the combined elements directly. A
      requirement of 0.5~1 MUrad for the standard deviation of the tip/tilt error is
      adequate.

PMID- 22614598
TI  - Thermo-optic coefficients study in KGd(WO4)2 and KY(WO4)2 by a modified minimum
      deviation method.
AB  - Thermo-optic coefficients anisotropy was characterized in monoclinic potassium
      (rare-earth) double tungstates KGd(WO4)2 and KY(WO4)2 in the spectral range of
      0.44-0.63 MUm by a modified minimum deviation method. This approach takes into
      account the changes in the shape and dimensions of the prismatic sample caused by
      the anisotropic thermal expansion effect under uniform heating together with the
      conventional measurements of minimum deviation angle. At room temperature at the
      wavelength of 633 nm, principal refractive indices for KGdW are n(p)=2.0135,
      n(m)=2.0458, and n(g)=2.0860, and for KYW they are n(p)=1.9979, n(m)=2.0396, and
      n(g)=2.0869. Optical axes position for KGdW (KYW) crystals is N(g) +/- 42.60
      (N(g) +/- 44.1 degrees ) in the N(p)-N(g) plane. For both crystals, all the
      thermo-optic coefficients are negative and equal dn(p)/dT=-10.6, dn(m)/dT=-8.4,
      and dn(g)/dT=-15.2 for KGdW, and dn(p)/dT=-10.1, dn(m)/dT=-7.3, and dn(g)/dT=-8.4
      for KYW [10(-6) K(-1)] (at 633 nm).

PMID- 22614599
TI  - High-precision three-dimensional shape reconstruction via digital refocusing in
      multi-wavelength digital holography.
AB  - Three-dimensional (3D) shape reconstructions and metrology measurements are often
      limited by depth-of-field constraints. Current focus-detection-based techniques
      are insufficient to profile out-of-focus 3D objects with high axial accuracy.
      Extended-focus imaging (EFI) techniques can improve the range and precision of
      such measurements. By incorporating digital refocusing with multiwavelength
      interferometry, a holographic imaging solution is presented in this paper to
      accurately measure 3D objects over a large depth range. Accuracy and
      repeatability of the proposed EFI technique are validated by digital simulations
      and refocusing experiments. A reconstruction example demonstrates the feasibility
      of high-precision 3D measurements of objects deeper than the system's classical
      depth of field.

PMID- 22614600
TI  - Simultaneous estimation of the 3-D soot temperature and volume fraction
      distributions in asymmetric flames using high-speed stereoscopic images.
AB  - An inverse radiation analysis using soot emission measured by a high-speed
      stereoscopic imaging system is described for simultaneous estimation of the 3-D
      soot temperature and volume fraction distributions in unsteady sooty flames. A
      new iterative reconstruction method taking self attenuation into account is
      developed based on the least squares minimum-residual algorithm. Numerical
      assessment and experimental measurement results of an ethylene/air diffusive
      flame show that the proposed method is efficient and capable of reconstructing
      the soot temperature and volume fraction distributions in unsteady flames. The
      accuracy is improved when self attenuation is considered.

PMID- 22614601
TI  - Ultrashort pulsed fiber laser welding and sealing of transparent materials.
AB  - In this paper, methods of welding and sealing optically transparent materials
      using an ultrashort pulsed (USP) fiber laser are demonstrated which overcome the
      limit of small area welding of optical materials. First, the interaction of USP
      fiber laser radiation inside glass was studied and single line welding results
      with different laser parameters were investigated. Then multiline scanning was
      used to obtain successful area bonding. Finally, complete four-edge sealing of
      fused silica substrates with a USP laser was demonstrated and the hermetic seal
      was confirmed by water immersion test. This laser microwelding technique can be
      extended to various applications in the semiconductor industry and precision
      optic manufacturing.

PMID- 22614602
TI  - Electromechanically driven variable-focus lens based on transparent dielectric
      elastomer.
AB  - Dielectric elastomers with low elastic stiffness and high dielectric constant are
      smart materials that produce large strains (up to 300%) and belong to the group
      of electroactive polymers. Dielectric elastomer actuators are made from films of
      dielectric elastomers coated on both sides with compliant electrode material.
      Poly(3,4-ethylenedioxythiophene) (PEDOT), which is known as a transparent
      conducting polymer, has been widely used as an interfacial layer or polymer
      electrode in polymer electronic devices. In this study, we propose the
      transparent dielectric elastomer as a material of actuator driving variable-focus
      lens system using PEDOT as a transparent electrode. The variable-focus lens
      module has light transmittance up to 70% and maximum displacement up to 450. When
      voltage is applied to the fabricated lens module, optical focal length is
      changed. We anticipate our research to be a starting point for new model of
      variable-focus lens system. This system could find applications in portable
      devices, such as digital cameras, camcorder, and cell phones.

PMID- 22614603
TI  - Generalized eikonal approximation for fast retrieval of particle size
      distribution in spectral extinction technique.
AB  - In retrieving particle size distribution from spectral extinction data, a
      critical issue is the calculation of extinction efficiency, which affects the
      accuracy and rapidity of the whole retrieval. The generalized eikonal
      approximation (GEA) method, used as an alternative to the rigorous Mie theory, is
      introduced for retrieval of the unparameterized shape-independent particle size
      distribution (PSD). To compute the extinction efficiency more efficiently, the
      combination of GEA method and Mie theory is adopted in this paper, which not only
      extends the applicable range of the approximation method but also improves the
      speed of the whole retrieval. Within the framework of the combined approximation
      method, the accuracy and limitations of the retrieval are investigated. Moreover,
      the retrieval time and memory requirement are also discussed. Both simulations
      and experimental results show that the combined approximation method can be
      successfully applied to retrieval of PSD when the refractive index is within the
      validity range. The retrieval results we present demonstrate the high reliability
      and stability of the method. By using this method, we find the complexity and
      computation time of the retrieval are significantly reduced and the memory
      resources can also be saved effectively, thus making this method more suitable
      for online particle sizing.

PMID- 22614604
TI  - Color image security system using double random-structured phase encoding in
      gyrator transform domain.
AB  - A novel method for encoding color information based on a double random phase mask
      and a double structured phase mask in a gyrator transform domain is proposed. The
      amplitude transmittance of the Fresnel zone plate is used as structured phase
      mask encoding. A color image is first segregated into red, green, and blue
      component images. Each of these component images are then independently encrypted
      using first a random phase mask placed at the image plane and transmitted through
      the first structured phase mask. They are then encoded by the first gyrator
      transform. The resulting information is again encrypted by a second random phase
      mask placed at the gyrator transform plane and transmitted through the second
      structured phase mask, and then encoded by the second gyrator transform. The
      system parameters of the structured phase mask and gyrator transform in each
      channel serve as additional encryption keys and enlarge the key space. The
      encryption process can be realized with an electro-optical hybrid system. The
      proposed system avoids problems arising from misalignment and benefits of a
      higher space-bandwidth product. Numerical simulations are presented to confirm
      the security, validity, and possibility of the proposed idea.

PMID- 22614605
TI  - Modeling optical microfiber loops for seawater sensing.
AB  - Based on resonant and waveguiding properties of optical microfiber loops, we
      theoretically investigated silica microfiber loop resonators (MLRs) for
      refractive index (RI) and salinity sensing of seawater. Dependences of
      sensitivity and detection limit on probing wavelength, fiber diameter, and ring
      diameter are calculated with typical parameters of seawater. Our results show
      that the sensitivity of MLRs increases with the increasing wavelength and the
      decreasing diameter of the microfiber. Bending loss and absorption loss are both
      important factors to determine the detection limit. By optimizing the parameters
      of the sensing system, RI sensitivity and salinity detection limit can reach 10(
      6) RI units (RIU) and 10(-2) 0/00 (10 ppm), respectively. The model presented
      here may be helpful for developing microscale fiber sensors for seawater
      detection with high sensitivity, low detection limit, and miniaturized sizes.

PMID- 22614606
TI  - Tunable liquid crystal microlens array using hole patterned electrode structure
      with ultrathin glass slab.
AB  - A configuration of hole patterned electrode liquid crystal microlens array with
      an ultrathin glass slab was fabricated. To reduce the fringing electric field
      effect and avoid the occurrence of disclination lines, an ultrathin glass slab
      was introduced between the patterned electrode and liquid crystal layer. The
      glass slab thickness played an important role in effecting the optical
      performance of the liquid crystal microlens array. An optimum thickness of 30 MUm
      was selected employing numerical simulation method. Using this method, we
      demonstrated a microlens array that greatly improved the phase profile and focus
      power. The dynamic focal range of the liquid crystal microlens array may extend
      from <1.2 mm to >8 mm and the minimum diameter of the focus spot could be as
      small as 15 um.

PMID- 22614607
TI  - Complex optical index of single wall carbon nanotube films from the near-infrared
      to the terahertz spectral range.
AB  - We retrieve the complex optical index of single-walled carbon nanotube (CNT)
      films in the 0.6-800 MUm spectral range. Results are obtained from a complete set
      of optical measurements, reflection and transmission, of free-standing CNT films
      using time domain spectroscopy in the terahertz (THz) and Fourier transform
      infrared (IR) spectroscopy in the visible-IR. Based on a Drude-Lorentz model, our
      results reveal a global metallic behavior of the films in the IR, and confirm
      their high optical index in the THz range.

PMID- 22614608
TI  - Polarization resolved classification of winter road condition in the near
      infrared region.
AB  - Three different configurations utilizing polarized short-wave infrared light to
      classify winter road conditions have been investigated. In the first
      configuration, polarized broadband light was detected in the specular and
      backward directions, and the quotient between the detected intensities was used
      as the classification parameter. Best results were obtained for the SS
      configuration. This sensor was shown to be able to distinguish between the smooth
      road conditions of water and ice from the diffuse road conditions of snow and dry
      asphalt with a probability of wrong classification as low as 7%. The second
      sensor configuration was a pure backward architecture utilizing polarized light
      with two distinct wavelengths. This configuration was shown to be effective for
      the important problem of distinguishing water from ice with a probability of
      wrong classification of only 1.5%. The third configuration was a combination of
      the two previous ones. This combined sensor utilizing bispectral illumination and
      bidirectional detection resulted in a probability of wrong classification as low
      as 2% among all four surfaces.

PMID- 22614609
TI  - Compact micromachined infrared bandpass filters for planetary spectroscopy.
AB  - The future needs of space-based, observational planetary and astronomy missions
      include low mass and small volume radiometric instruments that can operate in
      high-radiation and low-temperature environments. Here, we focus on a central
      spectroscopic component, the bandpass filter. We model the bandpass response of
      the filters to target the wavelength of the resonance peaks at 20, 40, and 60 um
      and report good agreement between the modeled and measured response. We present a
      technique of using standard micromachining processes for semiconductor
      fabrication to make compact, free-standing, resonant, metal mesh filter arrays
      with silicon support frames. The process can be customized to include multiple
      detector array architectures, and the silicon frame provides lightweight
      mechanical support with low form factor.

PMID- 22614610
TI  - Representation of freeform surfaces suitable for optimization.
AB  - To represent the freeform surface shape, the axially asymmetric quadric and a new
      set of the orthogonal polynomials are introduced. In this representation, surface
      tilt, paraxial properties, and higher order surface shape are clearly separated.
      With this representation, the optimization process can be simple and efficient.

PMID- 22614611
TI  - Interferometric spatial coherence tomography: focusing fringe contrast to planes
      of interest using a quasi-monochromatic structured light source.
AB  - Interferograms of plane parallel optical flats are hard to interpret when
      acquired with coherent illumination because of the complex fringe pattern
      resulting from the superposition of three main contributions, namely from the
      reference surface and the front and back sample surfaces. We illuminate the
      sample by a field of high temporal and specially tailored partial spatial
      coherence. This limits the fringe contrast to sheets of adjustable position and
      thickness along the axis of the interferometer. We outline the technique and
      demonstrate its application together with phase shifting interferometry to
      extract the topography of front and back surfaces of transparent samples.

PMID- 22614612
TI  - Ronchi test with equivalent wavelength.
AB  - In this work we present an experimental proposal to evaluate optical surfaces
      with high slopes or with infrared wavelengths based on the Ronchi test as well as
      on the concept of equivalent wavelength. A spatial modulator is used in the
      implementation of the Ronchi test, and a white LED with different color filters
      is employed in order to generate different wavelengths. Two Ronchigrams with
      incoherent light, each one for a different color, are registered and
      computationally processed, thus generating a third one with an equivalent
      wavelength. The results obtained show that it is possible to generate patterns
      with traditional rulings and substructured sequences of Katyl. Additionally, we
      discuss some of the limitations of employing different rulings. Finally, we found
      that appropriate image enhancing algorithms allow us to improve the visibility of
      the resulting fringes and thus obtain a better analysis.

PMID- 22614613
TI  - Wide angle conoscopic interference patterns in uniaxial crystals.
AB  - The fringe pattern obtained when a divergent (or convergent) beam goes through a
      sample of birefringent crystal between two crossed polarizers contains
      information that is inherent to the crystalline sample under study. The formation
      of fringe patterns is analyzed from distinct approaches and with different
      degrees of approximation considering cones of light of large numerical aperture.
      We obtain analytic explicit formulas of the phase shift on the screen and compare
      them with the exact numerical solution. The results obtained are valid for
      arbitrary orientation of the optical axis and are not restricted either to low
      birefringence or to small angles of incidence. Moreover, they enable the
      extraction of the main features related to the characterization of uniaxial
      crystal slabs, such as the optical axis tilt angle and the principal refractive
      indices.

PMID- 22614614
TI  - Intense red upconversion emission of Yb/Tm/Ho triply-doped tellurite glasses.
AB  - By conventional melting and quenching methods, 3Yb2O3-0.2Tm2O3-xHo2O3 (wt%,
      x=0.2~1.2) was doped into an easily fiberized tellurite glass with composition of
      78TeO2-10ZnO-12Na2O (mol%) to form YTH-TZN78 glasses. Under 976 nm excitation,
      the direct sensitizing effect of Yb ions (Yb->Ho) and indirect sensitizing and
      self-depopulating effects of Tm ions (Yb->Tm->Ho) were found to present intense
      red upconversion emission at 657 nm (Red, Ho:5F5->5I8) and were responsible for
      the absence of the usually observed 484 nm emission (Blue, Tm:1G4->3H36).
      Regardless of the dopant concentration of Ho ions, the intensity of the red
      emission at 657 nm (Red, Ho:5F5->5I8) is about three times stronger than that of
      the green one at 543 nm (Green, Ho:5S2->5I8). For this certain red emission at
      657 nm, 0.4 wt% Ho2O3-doped YTH-TZN78 glass was found to present the highest
      emission intensity and is therefore determined as a promising active tellurite
      glass for red fiber laser development.

PMID- 22614615
TI  - Fluidic sensor based on the side-opened and suspended dual-core fiber.
AB  - For accelerating the response and enhancing the sensitivity simultaneously, a
      novel fluidic sensor based on a side-opened and suspended dual-core fiber and
      dual-beam interference detection mechanism is first explored and analyzed here.
      The side opening ensures a fast response by allowing fluidic analyte to approach
      the fiber core laterally. The dual-beam Mach-Zehnder interferemetry provides a
      relative higher sensitivity. Calculation results show that a sensitivity of
      2.1*10(-6) refractive index unit (RIU) within a response time of 10 s could be
      achievable, which reflects its potential impact on constructing a fluid
      refractometer for fast-response and high-sensitivity detection. Moreover, the
      relationship of the sensing sensitivity and the detected dynamic range of this
      suspended dual-core fiber structure, polarization, and the transmitting waveband
      are also analyzed.

PMID- 22614616
TI  - Birefringence analysis of segmented cladding fiber.
AB  - We present a full-vectorial modal analysis of a segmented cladding fiber (SCF).
      The analysis is based on the H-field vectorial finite element method (VFEM)
      employing polar mesh geometry. Using this method, we have analyzed the circular
      SCF and the elliptical SCF. We have found that the birefringence of the circular
      SCF is very small (1.0*10(-8)). Birefringence of a highly elliptical SCF can be
      altered to some extent by the number of segments and duty cycle of segmentation
      in the segmented cladding. However, the change is not profound. The analysis
      shows that the circular SCF possesses low birefringence and that the segmented
      cladding does not add any significant birefringence in an elliptical fiber. This
      result strongly indicates that small deviations in the segmented cladding
      parameters arising from fabrication process do not significantly affect the
      birefringence of the fiber.

PMID- 22614617
TI  - Prevention: Pediatric ECG screening.

PMID- 22614619
TI  - Anticoagulation therapies: Warfarin vs aspirin in HF.

PMID- 22614620
TI  - Relationship between sleep quality and the level and pattern of BP.

PMID- 22614618
TI  - The importance of the endothelium in atherothrombosis and coronary stenting.
AB  - Deployment of drug-eluting stents instead of bare-metal stents has dramatically
      reduced restenosis rates, but rates of very late stent thrombosis (>1 year
      postimplantation) have increased. Vascular endothelial cells normally provide an
      efficient barrier against thrombosis, lipid uptake, and inflammation. However,
      endothelium that has regenerated after percutaneous coronary intervention is
      incompetent in terms of its integrity and function, with poorly formed cell
      junctions, reduced expression of antithrombotic molecules, and decreased nitric
      oxide production. Delayed arterial healing, characterized by poor
      endothelialization, is the primary cause of late (1 month-1 year
      postimplantation) and very late stent thrombosis following implantation of drug
      eluting stents. Impairment of vasorelaxation in nonstented proximal and distal
      segments of stented coronary arteries is more severe with drug-eluting stents
      than bare-metal stents, and stent-induced flow disturbances resulting in complex
      spatiotemporal shear stress can also contribute to increased thrombogenicity and
      inflammation. The incompetent endothelium leads to late stent thrombosis and the
      development of in-stent neoatherosclerosis. The process of neoatherosclerosis
      occurs more rapidly, and more frequently, following deployment of drug-eluting
      stents than bare-metal stents. Improved understanding of vascular biology is
      crucial for all cardiologists, and particularly interventional cardiologists, as
      maintenance of a competently functioning endothelium is critical for long-term
      vascular health.

PMID- 22614622
TI  - Acute coronary syndromes: Early metabolic modulation--a solution for MI?

PMID- 22614623
TI  - Isogeneic comparison of primary and metastatic lung cancer identifies CX3CR1 as a
      molecular determinant of site-specific metastatic diffusion.
AB  - Metastatic diffusion is a major adverse prognostic determinant in lung cancer,
      that is ultimately responsible for significant morbidity, organ failure and
      death. Chemokine signaling pathways are known to guide site-specific metastatic
      spread in solid tumours. However, little is known about the contribution of
      CX3CR1 in the systemic dissemination of lung cancer. Syngeneic primary lung
      cancer/metastasis tissue microarray slides were constructed using 98 post-mortem
      specimens taken from patients with untreated lung cancer and immunostained for
      CX3CR1. Clinicopathological correlation between CX3CR1 expression and patient
      demographics, tumour histology, stage and pattern of metastatic spread was
      performed using chi2 test. CX3CR1 immunopositivity was significantly higher in
      non-small cell lung cancer (NSCLC) compared to small cell (SCLC) primary
      (p<0.001) and secondary tumours (p<0.001), with >75% of the metastatic sites
      staining positively in NSCLC. CX3CR1 positivity was significantly associated with
      stage and number of metastatic sites (p=0.03). At patients' death CX3CR1-negative
      lung adenocarcinomas were more likely to have spread to the brain and the liver
      (p=0.01). CX3CR1 is upregulated in NSCLC metastatic disease and its expression in
      primary lung tumours relates inversely to organotropic spread of cancer cells to
      the brain and the liver.

PMID- 22614624
TI  - Exploring a road map to counter misconceptions about the cervicovaginal
      microbiome and disease.
AB  - Urogenital diseases, especially infection and cancer, are major causes of death
      and morbidity in females. Yet, millions of women in the developing world have no
      access to basic urogynecological care, and the diagnosis and treatment of
      widespread aberrant bacterial conditions (bacterial vaginosis [BV] and aerobic
      vaginitis [AV]) remain suboptimal the world over. Samples from women living in
      resource-disadvantaged and developed countries have been analyzed by high
      throughput sequencing to reveal the diversity of bacteria in the vagina, how
      rapidly the bacterial population fluctuates over time, and how rapidly the switch
      occurs between healthy and aberrant conditions. Unfortunately, clinical
      diagnostic methods are inefficient and too often outdated therapies are
      administered. The net result is suboptimal care and recurrent disease that
      adversely affects the quality of life. This viewpoint outlines a scientific and
      translational road map designed to improve the cervicovaginal health and
      treatment of disease. This comprises (1) improving education of women and
      physicians on the vaginal microbiota; (2) having agencies target funding for
      research to improve diagnosis and test new therapies; and (3) making sure that
      new approaches are accessible in developing countries, empowering to women, and
      are acceptable and appropriate for different populations.

PMID- 22614625
TI  - Physiologic uterine inflammation and labor onset: integration of endocrine and
      mechanical signals.
AB  - The mechanisms underlying the preparation of the uterus for labor are not fully
      understood. Our previous studies have shown that during pregnancy, the uterine
      muscle (myometrium) undergoes dramatic phenotypic modulation culminating in term
      labor. The current review will discuss the cellular mechanisms involved in the
      regulation of myometrial activity and its modulation by endocrine signals and by
      mechanical stimulation of the uterus by the growing fetus. In particular, the
      contribution of uterine inflammation to the onset of labor will be described. We
      provide evidence that increased production of cytokines/chemokines in pregnant
      myometrium is associated with uterine occupancy and regulated by progesterone,
      suggesting the integration of mechanical and endocrine signals. Myometrial cells
      can actively participate in the inflammatory process in the uterus through the
      release of multiple proinflammatory cytokines and chemokines, providing a strong
      signal for activation of immune cells, their subsequent infiltration into
      pregnant uterus, and the initiation of labor.

PMID- 22614627
TI  - The glomerular filtration barrier function:  new concepts.
AB  - PURPOSE OF REVIEW: Each day, the human kidneys filter about 140 l of primary
      urine from plasma. Although this ultrafiltrate is virtually free of plasma
      protein, the glomerular filter never clogs under physiological conditions. Upto
      today it is still not entirely resolved as to how the kidney accomplishes this
      extraordinary task. Most of the proposed models for glomerular filtration have
      not considered electrical effects. RECENT FINDINGS: In micropuncture studies, we
      have directly measured an electrical field across the glomerular filtration
      barrier. This potential difference is most likely generated by forced passage of
      the ionic solution of the plasma across the charged glomerular filter
      ('electrokinetic potential'). As all plasma proteins are negatively charged, the
      electrical field across the glomerular filtration barrier is predicted to drive
      plasma proteins from the filter toward the capillary lumen by electrophoresis.
      SUMMARY: In this review, we examine our novel model for glomerular filtration in
      more detail. We outline the physical mechanisms by which electrokinetic effects
      (streaming potentials) are generated. We investigate the potential impact of the
      electrical field on the passage of albumin across the glomerular filtration
      barrier. We review the mathematical heteroporous model including electrical
      effects and analyse a selection of experimental studies for indications that
      electrical effects influence glomerular permeability significantly.

PMID- 22614628
TI  - Novel findings and future directions on the genetics of hypertension.
AB  - PURPOSE OF REVIEW: Modern molecular techniques are identifying pathways and genes
      involved in the pathogenesis of the complex disorder essential hypertension. This
      review provides an overview of genetic methodologies and recent results in the
      study of high blood pressure (BP), hypertension-attributed nephropathy, and
      related intermediate phenotypes. RECENT FINDINGS: Candidate gene studies have
      implicated aberrations in ion channels, ion channel regulation, aldosterone
      signaling, vasoconstriction and inflammation in essential hypertension; genome
      wide association studies (GWAS) have detected more than 50 BP loci, most
      previously unsuspected in essential hypertension. Mapping by admixture linkage
      disequilibrium (MALD; or admixture mapping) recently led to a major breakthrough
      in hypertension-attributed kidney disease in African Americans, demonstrating the
      role of the apolipoprotein L1 (APOL1) and nonmuscle myosin heavy chain 9 (MYH9)
      genes in this primary kidney disease residing in the spectrum of focal segmental
      glomerulosclerosis. GWAS have detected associations between kidney function and
      UMOD and SHROOM3. SUMMARY: Genetic studies confirm that 'essential hypertension'
      consists of disparate mechanisms that ultimately lead to elevations in systemic
      BP. The cause of hypertension in the majority of cases remains unknown. It is
      anticipated that epigenetic phenomena, rare exonic mutations, and interactions
      with environmental factors make additional contributions.

PMID- 22614629
TI  - Direct and facile synthesis of carbon substituted alkylhydroxy derivatives of
      cobalt bis(1,2-dicarbollide), versatile building blocks for synthetic purposes.
AB  - Reactions of lithiated cobalt bis(1,2-dicarbollide)(1(-)) anion (1(-)) in
      presence of paraformaldehyde, ethylene oxide or trimethylene oxide led to the
      substitution of 1(-) at the C-atoms resulting in the high yield formation of
      monosubstituted alkylhydroxy derivatives [(1-HO(CH(2))(n)-1,2
      C(2)B(9)H(10))(1',2'-C(2)B(9)H(11))-3,3'-Co(III)](-) (n = 1-3) isolated as
      caesium salts (Cs2, Cs3, Cs4) along with disubstituted products of general
      formulation [(HO(CH(2))(n)-1,2-C(2)B(9)H(10))(2)-3,3'-Co(III)](-) (n = 1-3) (Cs5,
      Cs6 and Cs7). Disubstituted compounds are in fact a mixture of diastereoisomers
      denoted as 1,1'-anti(rac-), 1,2'-syn- and in case of Cs6 and Cs7 also 1,2-vicinal
      isomer, from which only the anti-isomer could be isolated in pure form in case of
      shorter chain compounds Cs5 and Cs6. All these alkylhydroxy derivatives can serve
      as versatile precursors for the generation of a variety of functional molecules.
      Thus, reaction of Me(3)NH4 with NaH and one equivalent of POCl(3) provided after
      hydrolysis the phosphorylated [(1-(HO)(2)P(O)OC(3)H(6)-1,2-C(2)B(9)H(10))(1',2'
      C(2)B(9)H(11))-3,3'-Co(III)](-) derivative, isolated in the form of
      trimethylammonium salt, Me(3)NH8 as the main product whereas reaction with half
      of the equivalent produces a high yield of phosphoric acid diester (Me(3)NH)(2)9
      comprising in its structure two cages connected via propyl spacers to the central
      part. The calcium salt Ca(10)(2) of bridged ion [MU-(HOP(O)(OC(3)H(6))(2))-(1,2
      C(2)B(9)H(10))(2)-3,3'-Co(III)](-) resulted from reaction of Me(3)NH7 with NaH
      and one equivalent of POCl(3) followed by hydrolysis and addition of CaCl(2). All
      new compounds were characterized by multinuclear NMR spectroscopy and mass
      spectrometry and the structure of Me(3)NH3 and that of the respective salts of
      the pure anti-stereoisomer of dialkylhydroxy derivatives Cs5 and Me(3)NH6 were
      established by X-ray crystallography.

PMID- 22614626
TI  - Management of mineral and bone disorder after kidney transplantation.
AB  - PURPOSE OF REVIEW: Mineral and bone disorders (MBDs), inherent complications of
      moderate and advanced chronic kidney disease, occur frequently in kidney
      transplant recipients. However, much confusion exists about the clinical
      application of diagnostic tools and preventive or treatment strategies to correct
      bone loss or mineral disarrays in transplanted patients. We have reviewed the
      recent evidence about prevalence and consequences of MBD in kidney transplant
      recipients and examined diagnostic, preventive and therapeutic options to this
      end. RECENT FINDINGS: Low turnover bone disease occurs more frequently after
      kidney transplantation according to bone biopsy studies. The risk of fracture is
      high, especially in the first several months after kidney transplantation.
      Alterations in minerals (calcium, phosphorus and magnesium) and biomarkers of
      bone metabolism (parathyroid hormone, alkaline phosphatase, vitamin D and FGF-23)
      are observed with varying impact on posttransplant outcomes. Calcineurin
      inhibitors are linked to osteoporosis, whereas steroid therapy may lead to both
      osteoporosis and varying degrees of osteonecrosis. Sirolimus and everolimus might
      have a bearing on osteoblast proliferation and differentiation or decreasing
      osteoclast-mediated bone resorption. Selected pharmacologic interventions for the
      treatment of MBD in transplant patients include steroid withdrawal, and the use
      of bisphosphonates, vitamin D derivatives, calcimimetics, teriparatide,
      calcitonin and denosumab. SUMMARY: MBD following kidney transplantation is common
      and characterized by loss of bone volume and mineralization abnormalities, often
      leading to low turnover bone disease. Although there are no well established
      therapeutic approaches for management of MBD in renal transplant recipients,
      clinicians should continue individualizing therapy as needed.

PMID- 22614630
TI  - Maximal thermogenic capacity and non-shivering thermogenesis in the South
      American subterranean rodent Ctenomys talarum.
AB  - Subterranean rodents inhabit closed tunnel systems that are hypoxic and
      hypercapnic and buffer aboveground ambient temperature. In contrast to other
      strictly subterranean rodents, Ctenomys talarum exhibits activity on the surface
      during foraging and dispersion and hence, is exposed also to the aboveground
      environment. In this context, this species is a valuable model to explore how the
      interplay between underground and aboveground use affects the relationship among
      basal metabolic rate (BMR), cold-induced maximum metabolic rate (MMR), shivering
      (ST), and non-shivering thermogenesis (NST). In this work, we provide the first
      evidence of the presence of NST, including the expression of uncoupling proteins
      in brown adipose tissue (BAT), and shivering thermogenesis in Ctenomys talarum, a
      species belonging to the most numerous subterranean genus, endemic to South
      America. Our results show no differences in BMR, cold-induced MMR, and NST
      between cold- (15  degrees C) and warm- (25  degrees C) acclimated individuals.
      Furthermore, thermal acclimation had no effect on the expression of mitochondrial
      uncoupling protein 1 (UCP1) in BAT. Only cytochrome c oxidase (COX) content and
      activity increased during cold acclimation. When interscapular BAT was removed,
      NST decreased more than 30%, whereas cold-induced MMR remained unchanged. All
      together, these data suggest that cold-induced MMR reaches a maximum in warm
      acclimated individuals and so a probable ceiling in NST and UCP1 expression in
      BAT. Possible thermogenic mechanisms explaining the increase in the oxidative
      capacity, mediated by COX in BAT of cold-acclimated individuals and the role of
      ST in subterranean life habits are proposed.

PMID- 22614631
TI  - Using ipsilateral motor signals in the unaffected cerebral hemisphere as a signal
      platform for brain-computer interfaces in hemiplegic stroke survivors.
AB  - Brain-computer interface (BCI) systems have emerged as a method to restore
      function and enhance communication in motor impaired patients. To date, this has
      been applied primarily to patients who have a compromised motor outflow due to
      spinal cord dysfunction, but an intact and functioning cerebral cortex. The
      cortical physiology associated with movement of the contralateral limb has
      typically been the signal substrate that has been used as a control signal. While
      this is an ideal control platform in patients with an intact motor cortex, these
      signals are lost after a hemispheric stroke. Thus, a different control signal is
      needed that could provide control capability for a patient with a hemiparetic
      limb. Previous studies have shown that there is a distinct cortical physiology
      associated with ipsilateral, or same-sided, limb movements. Thus far, it was
      unknown whether stroke survivors could intentionally and effectively modulate
      this ipsilateral motor activity from their unaffected hemisphere. Therefore, this
      study seeks to evaluate whether stroke survivors could effectively utilize
      ipsilateral motor activity from their unaffected hemisphere to achieve this BCI
      control. To investigate this possibility, electroencephalographic (EEG) signals
      were recorded from four chronic hemispheric stroke patients as they performed (or
      attempted to perform) real and imagined hand tasks using either their affected or
      unaffected hand. Following performance of the screening task, the ability of
      patients to utilize a BCI system was investigated during on-line control of a one
      dimensional control task. Significant ipsilateral motor signals (associated with
      movement intentions of the affected hand) in the unaffected hemisphere, which
      were found to be distinct from rest and contralateral signals, were identified
      and subsequently used for a simple online BCI control task. We demonstrate here
      for the first time that EEG signals from the unaffected hemisphere, associated
      with overt and imagined movements of the affected hand, can enable stroke
      survivors to control a one-dimensional computer cursor rapidly and accurately.
      This ipsilateral motor activity enabled users to achieve final target accuracies
      between 68% and 91% within 15 min. These findings suggest that ipsilateral motor
      activity from the unaffected hemisphere in stroke survivors could provide a
      physiological substrate for BCI operation that can be further developed as a long
      term assistive device or potentially provide a novel tool for rehabilitation.

PMID- 22614632
TI  - Protective effects of atorvastatin against oxidized LDL-induced downregulation of
      KLF expression in EA.hy926 cells.
AB  - Kruppel-like transcription factors (KLFs) play a key role in both vascular
      development and pathophysiological processes, but little is known about the
      relationship between KLFs and oxidized low-density lipoprotein (ox-LDL). We
      investigated the effects of ox-LDL on KLF expression. Furthermore, since
      atorvastatin is commonly used to treat high cholesterol, we also examined the
      role of this drug in the regulation of KLF expression. The human umbilical vein
      endothelial cell line EA.hy926 was treated with atorvastatin and ox-LDL alone or
      in combination, and KLF expression was examined by DNA microarray, semi
      quantitative real-time PCR, western blot and immunofluorescence analyses.
      Atorvastatin upregulated KLF expression in EA.hy926 cells in both the quiescent
      and ox-LDL-induced inflammatory states, suggesting that KLFs were novel
      participants in the vascular endothelial dysfunction response to ox-LDL. Our
      study demonstrated that atorvastatin increased both the mRNA and protein levels
      of KLF in quiescent EA.hy926 cells. Moreover, atorvastatin counteracted the ox
      LDL-induced downregulation of KLF expression.

PMID- 22614633
TI  - Effects of exercise intensity on copy number and mutations of mitochondrial DNA
      in gastrocnemus muscles in mice.
AB  - The present study aimed to investigate the effects of exercise intensity on
      mitochondrial DNA (mtDNA) alterations of copy numbers and mutations in the
      gastrocnemii of mice. A total of 50 male mice were randomly divided into 5
      groups; control group (K) and groups A-D, which underwent 10,30,60 and 90 min of
      swimming per day, respectively. Samples were obtained after 20 weeks of exercise.
      Total DNA was collected to analyze mutations in the mtDNA displacement loop (D
      loop) regions. mtDNA content was quantified by real-time PCR. Point mutations,
      monobase insertions and deletions were observed in the mtDNA D-loop regions in
      the skeletal muscles of the mice. A deletion of 16,232 bp was found in certain
      groups. The mutation base of the control group was higher than that of the
      exercise groups. The exercise groups demonstrated significantly altered copy
      numbers; the 30 min exercise group had the highest copy number. These results
      suggest that moderate exercise intensity reduces mutations in the mtDNA D-loop
      regions, and enhances the copy number of mtDNA in the gastrocnemus muscles of
      mice.

PMID- 22614634
TI  - Optimal designs for composed models in pharmacokinetic-pharmacodynamic
      experiments.
AB  - We consider two frequently used PK/PD models and provide closed form descriptions
      of locally optimal designs for estimating individual parameters. In a novel way,
      we use these optimal designs and construct locally standardized maximin optimal
      designs for estimating any subset of the model parameters of interest. We do this
      by maximizing the minimal efficiency of the estimates across all relevant
      parameters so that these optimal designs are less dependent on the individual
      parameter or parameters of interest. Additionally, robust designs are proposed to
      further reduce the dependence on the nominal values of the parameters. We compare
      efficiencies of our proposed optimal designs with locally optimal designs and
      designs used in four real studies from the literature and show that our proposed
      designs provide advantages over those used in practice.

PMID- 22614635
TI  - Introduction to the GM crops special issue on biosafety, food and GM regulation.

PMID- 22614636
TI  - Gene technology regulation in Australia: a decade of a federal implementation of
      a statutory legal code in a context of constituent states taking divergent
      positions.
AB  - Gene technology is regulated in Australia by the Office of the Gene Technology
      Regulator (OGTR), a federal government agency with responsibility for managing
      health and environmental risks of GM organisms under the Gene Technology Act
      2000. The OGTR liaises with other national agencies, governments of States and
      Territories of Australia and local councils. Current national risk management
      regulation is the result of three decades of experience with oversight of gene
      technology. A major operational feature of Australian regulation is reliance on
      Institutional Biosafety Committees (IBCs) located within the regulated
      institutions. In 2009-2010 the OGTR managed 45 licenses relating to GM crop field
      trials, and inspected crop trials that included canola, wheat, barley, banana,
      sugarcane, cotton, Indian mustard and grapevines. States and Territories of
      Australia make decisions on market related (non-safety) issues, and adopt
      different political stances with respect to commercialization of GM crops. Some
      Australian states support environmental release of licensed GM crops (e.g.,
      Queensland), others ban them (Tasmania), while some have re-positioned
      themselves, after initially opposing commercialization, to currently allowing
      regulated commercial use (Victoria, Western Australia). Flexibility exhibited by
      the Australian regulatory system is facilitated by separation of political
      decision-making in the Gene Technology Ministerial Council away from the OGTR.

PMID- 22614637
TI  - There's a long, long trail a-winding: the complexities of GM foods regulation, a
      cautionary tale from the UK.
AB  - The evolution of the regulatory process for genetically modified (GM) food in the
      United Kingdom is reviewed from its formal inception in 1988 to the present,
      drawing out lessons which have been learned from a series of cases brought to the
      committee for approval. The unexpected but highly professional anti-GM campaign
      is described, and issues regarding public perceptions of risk are discussed.
      Recent failures to find a consensus solution in the United Kingdom are described,
      and a proposal is made for a way forward.

PMID- 22614638
TI  - Regulation of GM crops in Argentina.

PMID- 22614639
TI  - Estimates and implications of the costs of compliance with biosafety regulations
      in developing countries.
AB  - Estimating the cost of compliance with biosafety regulations is important as it
      helps developers focus their investments in producer development. We provide
      estimates for the cost of compliance for a set of technologies in Indonesia, the
      Philippines and other countries. These costs vary from US $100,000 to 1.7
      million. These are estimates of regulatory costs and do not include product
      development or deployment costs. Cost estimates need to be compared with
      potential gains when the technology is introduced in these countries and the
      gains in knowledge accumulate during the biosafety assessment process. Although
      the cost of compliance is important, time delays and uncertainty are even more
      important and may have an adverse impact on innovations reaching farmers.

PMID- 22614640
TI  - Carbachol-induced volume adaptation in mouse bladder and length adaptation via
      rhythmic contraction in rabbit detrusor.
AB  - The length-tension (L-T) relationships in rabbit detrusor smooth muscle (DSM) are
      similar to those in vascular and airway smooth muscles and exhibit short-term
      length adaptation characterized by L-T curves that shift along the length axis as
      a function of activation and strain history. In contrast to skeletal muscle, the
      length-active tension (L-T(a)) curve for rabbit DSM strips does not have a unique
      peak tension value with a single ascending and descending limb. Instead, DSM can
      exhibit multiple ascending and descending limbs, and repeated KCl-induced
      contractions at a particular muscle length on an ascending or descending limb
      display increasingly greater tension. In the present study, mouse bladder strips
      with and without urothelium exhibited KCl-induced and carbachol-induced length
      adaptation, and the pressure-volume relationship in mouse whole bladder displayed
      short-term volume adaptation. Finally, prostaglandin-E(2)-induced low-level
      rhythmic contraction produced length adaptation in rabbit DSM strips. A likely
      role of length adaptation during bladder filling is to prepare DSM cells to
      contract efficiently over a broad range of volumes. Mammalian bladders exhibit
      spontaneous rhythmic contraction (SRC) during the filling phase and SRC is
      elevated in humans with overactive bladder (OAB). The present data identify a
      potential physiological role for SRC in bladder adaptation and motivate the
      investigation of a potential link between short-term volume adaptation and OAB
      with impaired contractility.

PMID- 22614641
TI  - Unified framework for automated iris segmentation using distantly acquired face
      images.
AB  - Remote human identification using iris biometrics has high civilian and
      surveillance applications and its success requires the development of robust
      segmentation algorithm to automatically extract the iris region. This paper
      presents a new iris segmentation framework which can robustly segment the iris
      images acquired using near infrared or visible illumination. The proposed
      approach exploits multiple higher order local pixel dependencies to robustly
      classify the eye region pixels into iris or noniris regions. Face and eye
      detection modules have been incorporated in the unified framework to
      automatically provide the localized eye region from facial image for iris
      segmentation. We develop robust postprocessing operations algorithm to
      effectively mitigate the noisy pixels caused by the misclassification.
      Experimental results presented in this paper suggest significant improvement in
      the average segmentation errors over the previously proposed approaches, i.e.,
      47.5%, 34.1%, and 32.6% on UBIRIS.v2, FRGC, and CASIA.v4 at-a-distance databases,
      respectively. The usefulness of the proposed approach is also ascertained from
      recognition experiments on three different publicly available databases.

PMID- 22614642
TI  - Saliency detection in the compressed domain for adaptive image retargeting.
AB  - Saliency detection plays important roles in many image processing applications,
      such as regions of interest extraction and image resizing. Existing saliency
      detection models are built in the uncompressed domain. Since most images over
      Internet are typically stored in the compressed domain such as joint photographic
      experts group (JPEG), we propose a novel saliency detection model in the
      compressed domain in this paper. The intensity, color, and texture features of
      the image are extracted from discrete cosine transform (DCT) coefficients in the
      JPEG bit-stream. Saliency value of each DCT block is obtained based on the
      Hausdorff distance calculation and feature map fusion. Based on the proposed
      saliency detection model, we further design an adaptive image retargeting
      algorithm in the compressed domain. The proposed image retargeting algorithm
      utilizes multioperator operation comprised of the block-based seam carving and
      the image scaling to resize images. A new definition of texture homogeneity is
      given to determine the amount of removal block-based seams. Thanks to the
      directly derived accurate saliency information from the compressed domain, the
      proposed image retargeting algorithm effectively preserves the visually important
      regions for images, efficiently removes the less crucial regions, and therefore
      significantly outperforms the relevant state-of-the-art algorithms, as
      demonstrated with the in-depth analysis in the extensive experiments.

PMID- 22614643
TI  - SAR-based terrain classification using weakly supervised hierarchical Markov
      aspect models.
AB  - We introduce the hierarchical Markov aspect model (HMAM), a computationally
      efficient graphical model for densely labeling large remote sensing images with
      their underlying terrain classes. HMAM resolves local ambiguities efficiently by
      combining the benefits of quadtree representations and aspect models-the former
      incorporate multiscale visual features and hierarchical smoothing to provide
      improved local label consistency, while the latter sharpen the labelings by
      focusing them on the classes that are most relevant for the broader local image
      context. The full HMAM model takes a grid of local hierarchical Markov quadtrees
      over image patches and augments it by incorporating a probabilistic latent
      semantic analysis aspect model over a larger local image tile at each level of
      the quadtree forest. Bag-of-word visual features are extracted for each level and
      patch, and given these, the parent-child transition probabilities from the
      quadtree and the label probabilities from the tile-level aspect models, an
      efficient forwards-backwards inference pass allows local posteriors for the class
      labels to be obtained for each patch. Variational expectation-maximization is
      then used to train the complete model from either pixel-level or tile-keyword
      level labelings. Experiments on a complete TerraSAR-X synthetic aperture radar
      terrain map with pixel-level ground truth show that HMAM is both accurate and
      efficient, providing significantly better results than comparable single-scale
      aspect models with only a modest increase in training and test complexity.
      Keyword-level training greatly reduces the cost of providing training data with
      little loss of accuracy relative to pixel-level training.

PMID- 22614644
TI  - Video denoising, deblocking, and enhancement through separable 4-D nonlocal
      spatiotemporal transforms.
AB  - We propose a powerful video filtering algorithm that exploits temporal and
      spatial redundancy characterizing natural video sequences. The algorithm
      implements the paradigm of nonlocal grouping and collaborative filtering, where a
      higher dimensional transform-domain representation of the observations is
      leveraged to enforce sparsity, and thus regularize the data: 3-D spatiotemporal
      volumes are constructed by tracking blocks along trajectories defined by the
      motion vectors. Mutually similar volumes are then grouped together by stacking
      them along an additional fourth dimension, thus producing a 4-D structure, termed
      group, where different types of data correlation exist along the different
      dimensions: local correlation along the two dimensions of the blocks, temporal
      correlation along the motion trajectories, and nonlocal spatial correlation
      (i.e., self-similarity) along the fourth dimension of the group. Collaborative
      filtering is then realized by transforming each group through a decorrelating 4-D
      separable transform and then by shrinkage and inverse transformation. In this
      way, the collaborative filtering provides estimates for each volume stacked in
      the group, which are then returned and adaptively aggregated to their original
      positions in the video. The proposed filtering procedure addresses several video
      processing applications, such as denoising, deblocking, and enhancement of both
      grayscale and color data. Experimental results prove the effectiveness of our
      method in terms of both subjective and objective visual quality, and show that it
      outperforms the state of the art in video denoising.

PMID- 22614645
TI  - Magnification of label maps with a topology-preserving level-set method.
AB  - Image segmentation aims at partitioning an image into multiple segments. The
      application of this procedure produces a label map (also referred to as
      segmentation map) that classifies the pixels of the original image. In contrast
      to "natural" images, label maps are nominal-scale images, typically represented
      as integer-valued images. Nominal-scaled label maps can also appear as a
      representation of the raw data in areas, such as in geostatistics. In some
      applications, the original resolution of a label map does not suffice and a
      larger size map has to be generated. In this paper, we present a magnification
      algorithm for label maps and nominal images. The main property of our method is
      that it preserves the topology during the magnification process, which means that
      no isolated pixel vanishes. To the best of our knowledge, apart from nearest
      neighbor interpolation, the problem of label map magnification has not previously
      been addressed in the literature. The main idea of the proposed method is to
      accomplish a boundary refinement by smoothing the regions' boundaries on a finer
      grid. The method relies on well known methods, namely, the fundamental operations
      of morphological image processing-erosion and dilation-and the level-set method.
      The level-set method is well suited for our purposes since it does not depend on
      a parametrization and it is numerically stable. The topological flexibility of
      the level-set method-often found to be an advantage in applications-is a drawback
      here, since the topology of the original label map should be preserved. However,
      using the so-called simple point criterion from digital topology, one can adapt
      the conventional level-set method so that the topology will not be modified
      throughout the magnification procedure.

PMID- 22614646
TI  - Behavior subtraction.
AB  - Background subtraction has been a driving engine for many computer vision and
      video analytics tasks. Although its many variants exist, they all share the
      underlying assumption that photometric scene properties are either static or
      exhibit temporal stationarity. While this works in many applications, the model
      fails when one is interested in discovering changes in scene dynamics instead of
      changes in scene's photometric properties; the detection of unusual pedestrian or
      motor traffic patterns are but two examples. We propose a new model and
      computational framework that assume the dynamics of a scene, not its photometry,
      to be stationary, i.e., a dynamic background serves as the reference for the
      dynamics of an observed scene. Central to our approach is the concept of an
      event, which we define as short-term scene dynamics captured over a time window
      at a specific spatial location in the camera field of view. Unlike in our earlier
      work, we compute events by time-aggregating vector object descriptors that can
      combine multiple features, such as object size, direction of movement, speed,
      etc. We characterize events probabilistically, but use low-memory, low-complexity
      surrogates in a practical implementation. Using these surrogates amounts to
      behavior subtraction, a new algorithm for effective and efficient temporal
      anomaly detection and localization. Behavior subtraction is resilient to spurious
      background motion, such as due to camera jitter, and is content-blind, i.e., it
      works equally well on humans, cars, animals, and other objects in both
      uncluttered and highly cluttered scenes. Clearly, treating video as a collection
      of events rather than colored pixels opens new possibilities for video analytics.

PMID- 22614647
TI  - Localizing text in scene images by boundary clustering, stroke segmentation, and
      string fragment classification.
AB  - In this paper, we propose a novel framework to extract text regions from scene
      images with complex backgrounds and multiple text appearances. This framework
      consists of three main steps: boundary clustering (BC), stroke segmentation, and
      string fragment classification. In BC, we propose a new bigram-color-uniformity
      based method to model both text and attachment surface, and cluster edge pixels
      based on color pairs and spatial positions into boundary layers. Then, stroke
      segmentation is performed at each boundary layer by color assignment to extract
      character candidates. We propose two algorithms to combine the structural
      analysis of text stroke with color assignment and filter out background
      interferences. Further, we design a robust string fragment classification based
      on Gabor-based text features. The features are obtained from feature maps of
      gradient, stroke distribution, and stroke width. The proposed framework of text
      localization is evaluated on scene images, born-digital images, broadcast video
      images, and images of handheld objects captured by blind persons. Experimental
      results on respective datasets demonstrate that the framework outperforms state
      of-the-art localization algorithms.

PMID- 22614648
TI  - Adaptive membership functions for handwritten character recognition by Voronoi
      based image zoning.
AB  - In the field of handwritten character recognition, image zoning is a widespread
      technique for feature extraction since it is rightly considered to be able to
      cope with handwritten pattern variability. As a matter of fact, the problem of
      zoning design has attracted many researchers who have proposed several image
      zoning topologies, according to static and dynamic strategies. Unfortunately,
      little attention has been paid so far to the role of feature-zone membership
      functions that define the way in which a feature influences different zones of
      the zoning method. The result is that the membership functions defined to date
      follow nonadaptive, global approaches that are unable to model local information
      on feature distributions. In this paper, a new class of zone-based membership
      functions with adaptive capabilities is introduced and its effectiveness is
      shown. The basic idea is to select, for each zone of the zoning method, the
      membership function best suited to exploit the characteristics of the feature
      distribution of that zone. In addition, a genetic algorithm is proposed to
      determine-in a unique process-the most favorable membership functions along with
      the optimal zoning topology, described by Voronoi tessellation. The experimental
      tests show the superiority of the new technique with respect to traditional
      zoning methods.

PMID- 22614649
TI  - Generative Bayesian image super resolution with natural image prior.
AB  - We propose a new single image super resolution (SR) algorithm via Bayesian
      modeling with a natural image prior modeled by a high-order Markov random field
      (MRF). SR is one of the long-standing and active topics in image processing
      community. It is of great use in many practical applications, such as
      astronomical observation, medical imaging, and the adaptation of low-resolution
      contents onto high-resolution displays. One category of the conventional
      approaches for image SR is formulating the problem with Bayesian modeling
      techniques and then obtaining its maximum-a-posteriori solution, which actually
      boils down to a regularized regression task. Although straightforward, this
      approach cannot exploit the full potential offered by the probabilistic modeling,
      as only the posterior mode is sought. On the other hand, current Bayesian SR
      approaches using the posterior mean estimation typically use very simple prior
      models for natural images to ensure the computational tractability. In this
      paper, we present a Bayesian image SR approach with a flexible high-order MRF
      model as the prior for natural images. The minimum mean square error (MMSE)
      criteria are used for estimating the HR image. A Markov chain Monte Carlo-based
      sampling algorithm is presented for obtaining the MMSE solution. The proposed
      method cannot only enjoy the benefits offered by the flexible prior, but also has
      the advantage of making use of the probabilistic modeling to perform a posterior
      mean estimation, thus is less sensitive to the local minima problem as the MAP
      solution. Experimental results indicate that the proposed method can generate
      competitive or better results than state-of-the-art SR algorithms.

PMID- 22614650
TI  - 3-D object retrieval and recognition with hypergraph analysis.
AB  - View-based 3-D object retrieval and recognition has become popular in practice,
      e.g., in computer aided design. It is difficult to precisely estimate the
      distance between two objects represented by multiple views. Thus, current view
      based 3-D object retrieval and recognition methods may not perform well. In this
      paper, we propose a hypergraph analysis approach to address this problem by
      avoiding the estimation of the distance between objects. In particular, we
      construct multiple hypergraphs for a set of 3-D objects based on their 2-D views.
      In these hypergraphs, each vertex is an object, and each edge is a cluster of
      views. Therefore, an edge connects multiple vertices. We define the weight of
      each edge based on the similarities between any two views within the cluster.
      Retrieval and recognition are performed based on the hypergraphs. Therefore, our
      method can explore the higher order relationship among objects and does not use
      the distance between objects. We conduct experiments on the National Taiwan
      University 3-D model dataset and the ETH 3-D object collection. Experimental
      results demonstrate the effectiveness of the proposed method by comparing with
      the state-of-the-art methods.

PMID- 22614651
TI  - Partial differential equation-based approach for empirical mode decomposition:
      application on image analysis.
AB  - The major problem with the empirical mode decomposition (EMD) algorithm is its
      lack of a theoretical framework. So, it is difficult to characterize and evaluate
      this approach. In this paper, we propose, in the 2-D case, the use of an
      alternative implementation to the algorithmic definition of the so-called
      "sifting process" used in the original Huang's EMD method. This approach,
      especially based on partial differential equations (PDEs), was presented by Niang
      in previous works, in 2005 and 2007, and relies on a nonlinear diffusion-based
      filtering process to solve the mean envelope estimation problem. In the 1-D case,
      the efficiency of the PDE-based method, compared to the original EMD algorithmic
      version, was also illustrated in a recent paper. Recently, several 2-D extensions
      of the EMD method have been proposed. Despite some effort, 2-D versions for EMD
      appear poorly performing and are very time consuming. So in this paper, an
      extension to the 2-D space of the PDE-based approach is extensively described.
      This approach has been applied in cases of both signal and image decomposition.
      The obtained results confirm the usefulness of the new PDE-based sifting process
      for the decomposition of various kinds of data. Some results have been provided
      in the case of image decomposition. The effectiveness of the approach encourages
      its use in a number of signal and image applications such as denoising,
      detrending, or texture analysis.

PMID- 22614652
TI  - A novel recursive Bayesian learning-based method for the efficient and accurate
      segmentation of video with dynamic background.
AB  - Segmentation of video with dynamic background is an important research topic in
      image analysis and computer vision domains. In this paper, we present a novel
      recursive Bayesian learning-based method for the efficient and accurate
      segmentation of video with dynamic background. In the algorithm, each frame pixel
      is represented as the layered normal distributions which correspond to different
      background contents in the scene. The layers are associated with a confident term
      and only the layers satisfy the given confidence which will be updated via the
      recursive Bayesian estimation. This makes learning of background motion
      trajectories more accurate and efficient. To improve the segmentation quality,
      the coarse foreground is obtained via simple background subtraction first. Then,
      a local texture correlation operator is introduced to fill the vacancies and
      remove the fractional false foreground regions. Extensive experiments on a
      variety of public video datasets and comparisons with some classical and recent
      algorithms are used to demonstrate its improvements in both segmentation accuracy
      and efficiency.

PMID- 22614653
TI  - Semi-blind sparse image reconstruction with application to MRFM.
AB  - We propose a solution to the image deconvolution problem where the convolution
      kernel or point spread function (PSF) is assumed to be only partially known.
      Small perturbations generated from the model are exploited to produce a few
      principal components explaining the PSF uncertainty in a high-dimensional space.
      Unlike recent developments on blind deconvolution of natural images, we assume
      the image is sparse in the pixel basis, a natural sparsity arising in magnetic
      resonance force microscopy (MRFM). Our approach adopts a Bayesian Metropolis
      within-Gibbs sampling framework. The performance of our Bayesian semi-blind
      algorithm for sparse images is superior to previously proposed semi-blind
      algorithms such as the alternating minimization algorithm and blind algorithms
      developed for natural images. We illustrate our myopic algorithm on real MRFM
      tobacco virus data.

PMID- 22614654
TI  - Principal visual word discovery for automatic license plate detection.
AB  - License plates detection is widely considered a solved problem, with many systems
      already in operation. However, the existing algorithms or systems work well only
      under some controlled conditions. There are still many challenges for license
      plate detection in an open environment, such as various observation angles,
      background clutter, scale changes, multiple plates, uneven illumination, and so
      on. In this paper, we propose a novel scheme to automatically locate license
      plates by principal visual word (PVW), discovery and local feature matching.
      Observing that characters in different license plates are duplicates of each
      other, we bring in the idea of using the bag-of-words (BoW) model popularly
      applied in partial-duplicate image search. Unlike the classic BoW model, for each
      plate character, we automatically discover the PVW characterized with geometric
      context. Given a new image, the license plates are extracted by matching local
      features with PVW. Besides license plate detection, our approach can also be
      extended to the detection of logos and trademarks. Due to the invariance virtue
      of scale-invariant feature transform feature, our method can adaptively deal with
      various changes in the license plates, such as rotation, scaling, illumination,
      etc. Promising results of the proposed approach are demonstrated with an
      experimental study in license plate detection.

PMID- 22614655
TI  - Piecewise linear curve approximation using graph theory and geometrical concepts.
AB  - In this paper, a new methodology for curve approximation is presented. The method
      is suitable for both self-intersected and non self-intersected curves, it
      combines elements from graph theory and from elementary geometry and it is fully
      automated. More specifically, graph theory tools are utilized in order: 1) to
      remove the details that are irrelevant to the general shape of the curve under
      study and 2) to decompose the curve into non self-intersecting smaller curves.
      Then, each such smaller curve is processed via geometrical tools in order to
      approximate it efficiently with linear segments. Experimental results show that
      the proposed method compares well with several other methods of the same purpose.

PMID- 22614656
TI  - The use of bevacizumab among women with metastatic breast cancer: a survey on
      clinical practice and the ongoing controversy.
AB  - BACKGROUND: The US Food and Drug Administration's (FDA's) recent decision to
      remove the indication of bevacizumab for metastatic breast cancer (MBC) has
      fueled a debate in the breast cancer community. We conducted a survey to assess
      the perception of health care workers involved in the management of women with
      MBC on the FDA's decision to ascertain how it will affect practice and to
      determine how bevacizumab is commonly used in the community for MBC. METHODS: E
      mails were sent out between September and November 2010 using a database of 3000
      addresses maintained by the United Arab Emirates Cancer Congress. Individuals
      working for Roche or Genentech were excluded. The survey consisted of 22
      questions that were divided into 3 parts addressing each participant's
      demographic profile, their opinion of the FDA's decision, and the typical use of
      bevacizumab in the community in the setting of MBC. RESULTS: A total of 564
      participants were included in the final analysis, contributing to an 18.8%
      response rate. Of these participants, 14.6% were from the United States, 7.8%
      were from Canada, 31.1% were from Europe, 2.0% were from the United Arab
      Emirates, 11.1% were from Asia, and 33.3% were from other countries. The majority
      of participants believed progression-free survival to be a surrogate for overall
      survival, that cost played a role in the FDA's decision, and that the decision
      would adversely affect the future of newer drugs currently being investigated for
      MBC. The majority of participants indicated that they would use bevacizumab for
      triple receptor-negative MBC (46.5%), would use it in a first-line setting
      (44.7%), and would use it in combination with paclitaxel (51.9%). CONCLUSION: Our
      survey results highlight the discord between the opinion of community oncologists
      and the FDA's recent decision to withdraw the indication of bevacizumab for MBC.

PMID- 22614657
TI  - Prevalence of BRCA mutations in an unselected population of triple-negative
      breast cancer.
AB  - BACKGROUND: This study assessed BRCA1 and BRCA2 mutation prevalence in an
      unselected cohort of patients with triple-negative breast cancer (BC). METHODS:
      One hundred ninety-nine patients were enrolled. Triple negativity was defined as
      <1% estrogen and progesterone staining by immunohistochemistry and HER-2/neu not
      overexpressed by fluorescence in situ hybridization. Having given consent,
      patients had BRCA1 and BRCA2 full sequencing and large rearrangement analysis.
      Mutation prevalence was assessed among the triple-negative BC patients and the
      subset of patients without a family history of breast/ovarian cancer. Independent
      pathological review was completed on 50 patients. RESULTS: Twenty-one deleterious
      BRCA mutations were identified--13 in BRCA1 and 8 in BRCA2 (prevalence, 10.6%).
      In 153 patients (76.9%) without significant family history (first-degree or
      second-degree relatives with BC aged <50 years or ovarian cancer at any age), 8
      (5.2%) mutations were found. By using prior National Comprehensive Cancer Network
      (NCCN) guidelines recommending testing for triple-negative BC patients aged <45
      years, 4 of 21 mutations (19%) would have been missed. Two of 21 mutations (10%)
      would have been missed using updated NCCN guidelines recommending testing for
      triple-negative BC patients aged <60 years. CONCLUSIONS: The observed mutation
      rate was significantly higher (P = .0005) than expected based on previously
      established prevalence tables among patients unselected for pathology. BRCA1
      mutation prevalence was lower, and BRCA2 mutation prevalence was higher, than
      previously described. Additional mutation carriers would have met new NCCN
      testing guidelines, underscoring the value of the updated criteria. Study data
      suggest that by increasing the age limit to 65 years, all carriers would have
      been identified.

PMID- 22614658
TI  - Endothelial dysfunction: are we ready to heed the vasculature's early-warning
      signal?

PMID- 22614659
TI  - Association between troponin T and ICU mortality, a changing trend.
AB  - BACKGROUND: Initially elevated levels of troponin predict adverse outcomes in
      patients admitted to the intensive care unit (ICU). No research team has
      investigated the changes in concentration of cardiac troponin T (cTnT) during ICU
      stay and their association with patient outcome. OBJECTIVE: We investigated
      whether the change in cTnT levels during ICU stay could predict outcomes (death
      or survival). METHODS: In this cohort study, all patients admitted to the medical
      ICU (10 beds) from January to July 2008 were enrolled. Troponin levels were
      evaluated within the first 24 hours of ICU admission and on the fourth, seventh
      and 10th days after admission. RESULTS: The study population (135 patients) had a
      mean age of 60.9 +/- 21.5 years. The outcome was significantly different with
      regard to normal or elevated cTnT concentrations on the first and seventh days of
      follow up (p = 0.03 and 0.023, respectively). This difference was non-significant
      for cTnT levels on the fourth and 10th days after admission (p = 0.69 and 0.78,
      respectively). The change in cTnT levels was not significantly different between
      the deceased and discharged patients (p = 0.4). CONCLUSION: Changes in cTnT
      levels during ICU stay did not show a significant trend (power: 0.26). Patients
      whose cTnT levels were increased on the first and seventh days of ICU stay had a
      worse survival, which could be associated with cardiac events on admission or at
      specific times during the stay in ICU.

PMID- 22614660
TI  - Nebivolol therapy improves QTc and QTcd parameters in heart failure patients.
AB  - AIM: It has previously been shown that beta-blocker therapy reduces QT dynamics
      in heart failure patients. The aim of this study was to demonstrate this
      improvement with the third-generation beta-blocker, nebivolol. METHODS: A total
      of 72 heart failure patients with systolic dysfunction were included in the
      study. Corrected QT (QTc) and QT dispersion (QTcd) were measured manually by two
      independent observers at baseline and after nebivolol use (5 mg/day) in the first
      and third months of follow up. RESULTS: Both QTc and QTcd were found to be
      significantly reduced in the first (455.3 +/- 26.7 vs 441.2 +/- 25.7 ms, p <
      0.001 for QTc, and 65.6 +/- 5.3 vs 58.2 +/- 5.6 ms, p = 0.001 for QTcd) and third
      months (455.3 +/- 26.7 vs 436.0 +/- 28.7 ms, p < 0.001 for QTc, and 65.6 +/- 5.3
      vs 56.0 +/- 6.2 ms, p < 0.001 for QTcd) compared with baseline values.
      CONCLUSION: Nebivolol was associated with improved QT dynamics in heart failure
      patients with systolic dysfunction.

PMID- 22614661
TI  - Can cardiac surgery be performed safely on patients with haematological
      malignancies.
AB  - INTRODUCTION: Surgical strategy in patients with haematological malignancies must
      be planned and carried out with the specific aim of decreasing postoperative
      complications. The aim of this study was to present our experience on patients
      previously diagnosed with haematological malignancies who subsequently underwent
      cardiac surgery. We include data to assist other surgeons predict factors
      affecting postoperative morbidity and mortality in this group of patients.
      METHODS: Fifteen patients diagnosed with haematological malignancies who had
      cardiac surgery were retrospectively analysed. Eight patients had chronic
      lymphocytic leukaemia, six had non-Hodgkin's lymphoma and the rest had chronic
      myelocytic leukaemia. Coronary artery bypass graft surgery was performed on all
      of them. RESULTS: There were no hospital mortalities. The average follow-up
      period was 35 +/- 11 (23-56) months. Three patients required early postoperative
      re-operation because of excessive bleeding. No mortalities were seen in the early
      postoperative period. There were five (33%) deaths during the late follow-up
      period. Three patients were lost due to intracranial bleeding (confirmed by
      autopsy) in the 16th, 23rd and 38th months after surgery. The remaining two
      patients had sudden death in the eighth and 55th months from nondetectable
      causes. CONCLUSION: Cardiac surgery can be performed with acceptable early
      postoperative outcomes in patients with haematological malignancies. Intracranial
      bleeding is an important factor contributing to late mortality and patient
      selection and risk stratification are crucial to improving surgical benefits.

PMID- 22614662
TI  - The impact of cardiovascular risk factors on the site and extent of coronary
      artery disease.
AB  - BACKGROUND: In patients with coronary artery disease (CAD), the site and extent
      of coronary artery involvement in terms of proximal versus distal stenosis and
      multi- versus single-vessel disease have a crucial effect on patients' outcome.
      This study was designed to evaluate the relationship between cardiovascular risk
      factors and the site and extent of coronary artery involvement. METHODS: In this
      study of patients who had undergone coronary angiography in our hospital, 125
      with proximal lesions were enrolled as the case group (group 1) and an equal age-
      and gender-matched number of patients with non-proximal lesions were selected as
      the control group (group 2). The two groups were compared based on the presence
      or absence of diabetes mellitus (DM), hypercholesterolaemia,
      hypertriglyceridaemia, hypertension (HTN) and cigarette smoking. RESULTS: The
      frequency of DM was 33.6 and 10.4% in the case and control groups, respectively,
      which was statistically significant (p < 0.0001). However, the frequency of
      hypercholesterolaemia in the case and control groups was 30.4 and 29.6% (p =
      0.89), respectively; for hypertriglyceridaemia it was 19.2 and 16.8% (p = 0.062),
      respectively; for HTN it was 33.6 and 28.8% (p = 0.4), respectively; and for
      cigarette smoking it was 28.8 and 39.2% (p = 0.08), respectively, which were not
      statistically significant. Diabetic patients compared to non-diabetics had more
      multi-vessel disease (89.1 vs 61%, p < 0.0001, respectively), which was
      statistically significant. There was no relationship between
      hypercholesterolaemia, hypertriglyceridaemia, HTN and cigarette smoking and
      extent (multi-vessel involvement) of CAD (p = NS). CONCLUSION: Proximal and multi
      vessel involvement of the coronary arteries in patients with CAD was related to a
      history of DM but not of hypercholesterolaemia, HTN, cigarette smoking and
      hypertiglyceridaemia.

PMID- 22614663
TI  - The time-course changes of NT-proBNP and tissue Doppler indices in patients
      undergoing mitral valve replacement.
AB  - BACKGROUND: In severe mitral regurgitation, a subset of patients who are
      asymptomatic may develop left ventricular decompensation before changes in
      echocardiographic parameters become evident. Since N-terminal brain natriuretic
      peptide (NT-proBNP) is used to detect early heart failure, we hypothesised that
      NT-proBNP would be activated in patients with mitral regurgitation. METHODS:
      Patients submitted to surgery were prospectively evaluated over eight months in
      the Department of Cardiology at Inkosi Albert Luthuli Central Hospital. Control
      patients with severe mitral regurgitation were obtained from the outpatient
      clinic. In order to define their value in identifying left ventricular
      decompensation, NT-proBNP levels and tissue Doppler imaging (TDI) indices were
      simultaneously measured and compared with conventional echocardiographic indices
      at baseline and this was repeated at one week and at six weeks after valve
      replacement. RESULTS: Mean NT-proBNP levels were markedly elevated pre
      operatively in all surgical cases compared to controls (p = 0.0001). The
      diastolic E-mitral/E-annulus ratio, measured using TDI, was higher in the study
      group, indicating higher left ventricular filling pressure present in the study
      group. NT-proBNP levels increased further at one week after surgery and subsided
      at the six-week follow-up visit to levels similar to the control group. The TDI
      diastolic ratio also decreased at one week, and increased slightly again at the
      six-week follow up. These changes were accompanied by significant reduction in
      left atrium and left ventricular chamber dimensions with an increase in the
      ejection fraction from one to six weeks. CONCLUSION: Marked differences in mean
      NT-proBNP levels and TDI ratios between the study and control groups suggest that
      using TDI and NT-proBNP assays may detect covert left ventricular decompensation.

PMID- 22614664
TI  - Cohort studies of cardiovascular disease in the Seychelles, Tanzania and
      Mauritius.

PMID- 22614665
TI  - Presentation pattern and management of effusive-constrictive pericarditis in
      Ibadan.
AB  - BACKGROUND: Effusive-constrictive pericarditis is a syndrome in which
      constriction by the visceral pericardium occurs in the presence of a dense
      effusion in a free pericardial space. Treatment of this disease is problematic
      because pericardiocentesis does not relieve the impaired filling of the heart and
      surgical removal of the visceral pericardium is challenging. We sought to provide
      further information by addressing the evolution and clinico-pathological pattern,
      and optimal surgical management of this disease. METHODS: We conducted a
      prospective review of a consecutive series of five patients managed in the
      cardiothoracic surgery unit of University College Hospital, Ibadan, in the
      previous year, along with a general overview of other cases managed over a seven
      year period. This was followed by an extensive literature review with a special
      focus on Africa. RESULTS: The diagnosis of effusive-constrictive pericarditis was
      established on the basis of clinical findings of features of pericardial disease
      with evidence of pericardial effusion, and echocardiographic finding of
      constrictive physiology with or without radiological evidence of pericardial
      calcification. A review of our surgical records over the previous seven years
      revealed a prevalence of 13% among patients with pericardial disease of any type
      (11/86), 22% of patients presenting with effusive pericardial disease (11/50) and
      35% who had had pericardiectomy for constrictive pericarditis (11/31). All five
      cases in this series were confirmed by a clinical scenario of non-resolving
      cardiac impairment despite adequate open pericardial drainage. They all improved
      following pericardiectomy. CONCLUSION: Effusive-constrictive pericarditis as a
      subset of pericardial disease deserves closer study and individualisation of
      treatment. Evaluating patients suspected of having the disease affords clinicians
      the opportunity to integrate clinical features and non-invasive investigations
      with or without findings at pericardiostomy, to derive a management plan tailored
      to each patient. The limited number of patients in this series called for caution
      in generalisation. Hence our aim was to increase the sensitivity of others to
      issues raised and help spur on further collaborative studies to lay down
      guidelines with an African perspective.

PMID- 22614666
TI  - Risk factors for the development of pneumonia post cardiac surgery.
AB  - OBJECTIVES: Postoperative pneumonia is a devastating complication after cardiac
      surgery that increases morbidity and mortality. The objective of this study was
      to identify potential risk factors for the development of nosocomial pneumonia
      post cardiac surgery by the way of logistic regression analysis. DESIGN: Data of
      the last 162 patients undergoing cardiac surgery before November 2009 were
      retrospectively collected and analysed. RESULTS: The mean age of the patients was
      65.57 +/- 10.48 years and 83 (51%) were male. Postoperative pneumonia was
      diagnosed in 21 (13%) patients. The mean remaining time in the intensive care
      unit and mean length of hospitalisation were longer for patients with
      postoperative pneumonia. Pre-operative heart rate, previous diabetes mellitus,
      previous chronic obstructive pulmonary disease, postoperative urea, creatinine
      and potassium levels, extubation time, postoperative atrial fibrillation, and
      number of units of transfused packed red blood cells (pRBC) and fresh frozen
      plasma were associated with higher occurrence of postoperative pneumonia on
      univariate analysis. CONCLUSIONS: On logistic regression analysis, pRBC
      transfusion, previous chronic obstructive pulmonary disease and postoperative
      atrial fibrillation remained as independent predictors for the development of
      postoperative pneumonia.

PMID- 22614667
TI  - An audit of pregnant women with prosthetic heart valves at a tertiary hospital in
      South Africa: a five-year experience.
AB  - BACKGROUND: Cardiac disease in pregnancy is a common problem in under-resourced
      countries and a significant cause of maternal morbidity and mortality. A large
      proportion of patients with cardiac disease have prosthetic mechanical heart
      valve replacements, warranting prophylactic anticoagulation. AIM: To evaluate
      obstetric outcomes in women with prosthetic heart valves in an under-resourced
      country. METHODS: A retrospective chart review was performed of 61 pregnant
      patients with prosthetic valve prostheses referred to our tertiary hospital over
      a five-year period. RESULTS: Sixty-one (6%) of 1 021 pregnant women with A
      diagnosis of cardiac disease had prosthetic heart valves. Fifty-nine had
      mechanical valves and were on prophylactic anticoagulation therapy, three had
      stopped their medication prior to pregnancy and two had bioprosthetic valves.
      There were forty-one (67%) live births, two (3%) early neonatal deaths, 12 (20%)
      miscarriages and six (10%) stillbirths. Maternal complications included mitral
      valve thrombosis (n = 4), atrial fibrillation (n = 8), infective endocarditis (n
      = 6), caesarean section wound haematomas (n = 7), broad ligament haematoma (n =
      1) and warfarin embryopathy (n = 4). Haemorrhagic complications occurred in five
      patients and all five required blood transfusions. CONCLUSION: Prophylactic
      anticoagulation with warfarin in patients with mechanical heart valve prostheses
      was associated with high rates of maternal and neonatal complications, including
      significant foetal wastage in the first and early second trimesters of pregnancy.
      Health professionals providing care for pregnant women with prosthetic heart
      valves must consistently advise on family planning matters, adherence to
      anticoagulation regimes and consider the use of prophylactic anticoagulant
      regimens other than warfarin, particularly during the first trimester of
      pregnancy.

PMID- 22614668
TI  - Endothelial dysfunction: the early predictor of atherosclerosis.
AB  - Since the discovery in the 1980s that nitric oxide (NO) is in fact the elusive
      endothelium-derived relaxing factor, it has become evident that NO is not only a
      major cardiovascular signalling molecule, but that changes in its bioavailability
      are crucial in determining whether atherosclerosis will develop or not. Sustained
      high levels of harmful circulating stimuli associated with cardiovascular risk
      factors such as diabetes mellitus elicit responses in endothelial cells that
      appear sequentially, namely endothelial cell activation and endothelial
      dysfunction (ED). ED, characterised by reduced NO bioavailability, is now
      recognised by many as an early, reversible precursor of atherosclerosis. The
      pathogenesis of ED is multifactorial; however, oxidative stress appears to be the
      common underlying cellular mechanism in the ensuing loss of vaso-active,
      inflammatory, haemostatic and redox homeostasis in the body's vascular system.
      The role of ED as a pathophysiological link between early endothelial cell
      changes associated with cardiovascular risk factors and the development of
      ischaemic heart disease is of importance to basic scientists and clinicians
      alike.

PMID- 22614669
TI  - Blockade of the brain histamine H3 receptor by JNJ-39220675: preclinical PET
      studies with [11C]GSK189254 in anesthetized baboon.
AB  - RATIONALE: The preclinical characterization of a series of aryloxypyridine amides
      has identified JNJ-39220675 ((4-cyclobutyl-1,4-diazepan-1-yl)(6-(4
      fluorophenoxy)pyridin-3-yl)methanone) as a high-affinity histamine H(3) receptor
      antagonist and a candidate for further drug development particularly in the
      treatment of alcohol-related behaviors. OBJECTIVE: This study measured brain
      histamine H(3) receptor blockade by JNJ-39220675 (1 mg/kg) in the female baboon.
      METHODS: Positron emission tomography imaging and [(11)C]GSK189254, a reversible
      high-affinity radiotracer with specificity for the histamine H(3) receptor, was
      used to measure histamine H(3) receptor availability at baseline and after i.v.
      and oral administration of JNJ-39220675 (1 mg/kg) in the anesthetized baboon.
      Histamine H(3) receptor availability was estimated as the total distribution
      volume (V (T)) in brain regions. The sensitivity of [(11)C]GSK189254 binding to
      injected mass and carryover effects was determined. RESULTS: JNJ-39220675
      produces robust (ca. 90 %) blockade of [(11)C]GSK189254 binding after i.v. and
      oral administration. After oral administration of JNJ-39220675 (1 mg/kg), the
      fractional receptor occupancy was >0.9 at 90 min with a slight increase from 90
      to 240 min. Similar to prior studies in humans, V (T) was highly sensitive to the
      mass of GSK189254 with ED(50) estimated to be 0.16 MUg/kg. CONCLUSIONS: The
      robust blockade of binding of [(11)C]GSK189254 by JNJ-39220675 demonstrates that
      this compound readily penetrates the blood-brain barrier and occupies the
      histamine H(3) receptor after oral administration at low plasma concentrations
      (~1 ng/cc) supporting further drug development for alcohol addiction and other
      disorders. This study corroborates prior reports of the high sensitivity of
      [(11)C]GSK189254 to injected mass at doses >0.1 MUg/kg.

PMID- 22614670
TI  - Patient's global assessment of disease activity: what are we measuring?

PMID- 22614671
TI  - Association between serum stromal cell-derived factor-1alpha and long-term
      outcome of acute ischemic stroke.
AB  - BACKGROUND: Stromal cell-derived factor-1alpha (SDF-1alpha) provides neurotrophic
      support to neurons. In this prospective study, we investigated the association
      between SDF-1alpha and long-term outcome in patients with acute ischemic stroke.
      METHODS: This study included 104 patients with first-ever ischemic stroke,
      identified within 24 h of symptom onset. Serum samples were collected immediately
      after admission and 3 months thereafter, as well as from age- and sex-matched
      normal controls. The correlation between acute-stage serum SDF-1alpha and stroke
      severity were analyzed. Finally, the relationship between serum SDF-1alpha and
      long-term outcome was evaluated by multivariate analysis. RESULTS: Serum SDF
      1alpha levels were only higher in acute-stage stroke patients compared with the
      normal control group (p = 0.011). The serum SDF-1alpha level was increased in
      proportion to infarct volume (r = 0.220, p = 0.025) and initial National
      Institutes of Health Stroke Scale score (r = 0.275, p = 0.005). After adjustment
      for covariates, a high initial serum SDF-1alpha level (OR 1.167, p = 0.023) or
      second and third tertiles of SDF-1alpha level compared to first tertile (OR
      4.644, p = 0.044 and OR 9.396, p = 0.025, respectively) were significantly
      associated with a favorable long-term outcome. CONCLUSIONS: This prospective
      study demonstrated a correlation between serum SDF-1alpha and favorable long-term
      outcome in patients with acute ischemic stroke.

PMID- 22614672
TI  - DLC2/StarD13 plays a role of a tumor suppressor in astrocytoma.
AB  - Astrocytomas are tumors occurring in young adulthood. Astrocytic tumors can be
      classified into four grades according to histologic features: grades I, II, III
      and grade IV. Malignant tumors, those of grades III and IV, are characterized by
      uncontrolled proliferation, which is known to be regulated by the family of Rho
      GTPases. StarD13, a GAP for Rho GTPases, has been described as a tumor suppressor
      in hepatocellular carcinoma. In the present study, IHC analysis on grades I-IV
      brain tissues from patients showed StarD13 to be overexpressed in grades III and
      IV astrocytoma tumors when compared to grades I and II. However, when we mined
      the REMBRANDT data, we found that the mRNA levels of StarD13 are indeed higher in
      the higher grades but much lower than the normal tissues. Knocking down StarD13
      using siRNA led to a decrease in cell death and an increase in cell viability,
      proving that StarD13 is indeed a tumor suppressor in astrocytomas. This was found
      to be mainly through cell cycle arrest independently of apoptosis. Finally, we
      detected an increase in p-ERK in StarD13 knockdown cells, uncovering a potential
      link between Rho GTPases and ERK activation.

PMID- 22614673
TI  - Skin cancer: In melanoma ulceration, size matters.

PMID- 22614674
TI  - Review of extraperitoneal sacrocolpopexy as a technique for advanced uterine and
      vault prolapse.
AB  - PURPOSE OF REVIEW: This review is aimed to provide an update on the surgical
      techniques and complications of sacrocolpopexy procedures, and determine the role
      of minimally invasive techniques based on the most recent evidence. RECENT
      FINDINGS: The minimally invasive laparoscopic and robot-assisted alternatives to
      open abdominal sacrocolpopexy offer faster recovery, less complications and
      better cosmesis. However, this is suggested predominantly by retrospective
      comparative studies and no high-level evidence is available to date. Robot
      assisted sacrocolpopexy (RASC) has enabled surgeons to overcome the steep
      learning curve associated with laparoscopic sacrocolpopexy at the expense of a
      higher cost. Recent data, testing its potential advantages of reduced operative
      time and postoperative pain, have revealed contradictory results. A novel,
      totally retroperitoneal sacrocolpopexy procedure aimed to eliminate complications
      associated with transperitoneal access may become an option in patients
      unsuitable for minimally invasive techniques, but warrants further investigation.
      SUMMARY: The benefits of RASC must be weighed against the lack of current
      evidence to prove its superiority over conventional procedures in terms of faster
      recovery and cost-effectiveness. There is a need for better reporting of
      complications associated with these novel techniques and for long-term,
      randomized comparative data.

PMID- 22614675
TI  - Update on the surgical management of adenomyosis.
AB  - PURPOSE OF REVIEW: Adenomyosis is a benign gynaecological condition associated
      with menstrual symptoms and pelvic pain in premenopausal women, it has also been
      linked to subfertility. Improvement in ultrasound and MRI imaging has allowed
      accurate diagnosis of this condition prior to histological confirmation. Patients
      opting for surgical management need to be counselled regarding the surgical
      options available. This review summarizes the surgical management of adenomyosis
      and reviews the recent surgical developments. RECENT FINDINGS: For patients who
      wish to preserve their fertility, cytoreductive surgery is an option in centres
      with surgical expertise. Recently, modified surgical procedures to remove
      extensive adenomyosis known as an adenomyomectomy have been described. These
      operations may enhance subsequent fertility. SUMMARY: Access to accurate imaging
      modalities such as MRI and transvaginal ultrasound allows for adequate patient
      counselling preoperatively. Depending on the fertility requirements and the
      extent of adenomyosis, patients can be offered various surgical treatment options
      including laparoscopic hysterectomy or adenomyomectomy.

PMID- 22614676
TI  - Does screening for depression in primary care improve outcome?
AB  - 2012 marks one decade since the US Preventive Services Task Force recommended
      screening for depression. Advances since then include expanded understanding of
      the mechanisms underlying and influences of psychiatric disease on the
      development, course and outcomes of medical conditions. They also include
      collaborative care strategies to improve outcomes. However, the impact of such
      single disease approaches has been disappointing. Strategies that integrate
      management of multiple morbidities into primary care practice have greatly
      improved outcomes. Depression has been the only psychiatric condition
      incorporated into these strategies. Their expansion to integrate recognition and
      care of bipolar disease, anxiety disorders including PTSD, and substance abuse
      could further improve outcomes with modest marginal cost. Development of a
      screening and treatment monitoring instrument for multiple common psychiatric
      conditions is a prerequisite. One recently developed instrument, the M3, has the
      performance characteristics desirable, and provides opportunity to incorporate
      multiple common psychiatric conditions into multimorbidity integrated management.

PMID- 22614678
TI  - Lewis pair polymerization by classical and frustrated Lewis pairs: acid, base and
      monomer scope and polymerization mechanism.
AB  - Classical and frustrated Lewis pairs (LPs) of the strong Lewis acid (LA)
      Al(C(6)F(5))(3) with several Lewis base (LB) classes have been found to exhibit
      exceptional activity in the Lewis pair polymerization (LPP) of conjugated polar
      alkenes such as methyl methacrylate (MMA) as well as renewable alpha-methylene
      gamma-butyrolactone (MBL) and gamma-methyl-alpha-methylene-gamma-butyrolactone
      (gamma-MMBL), leading to high molecular weight polymers, often with narrow
      molecular weight distributions. This study has investigated a large number of
      LPs, consisting of 11 LAs as well as 10 achiral and 4 chiral LBs, for LPP of 12
      monomers of several different types. Although some more common LAs can also be
      utilized for LPP, Al(C(6)F(5))(3)-based LPs are far more active and effective
      than other LA-based LPs. On the other hand, several classes of LBs, when paired
      with Al(C(6)F(5))(3), can render highly active and effective LPP of MMA and gamma
      MMBL; such LBs include phosphines (e.g., P(t)Bu(3)), chiral chelating
      diphosphines, N-heterocyclic carbenes (NHCs), and phosphazene superbases (e.g.,
      P(4)-(t)Bu). The P(4)-(t)Bu/Al(C(6)F(5))(3) pair exhibits the highest activity of
      the LP series, with a remarkably high turn-over frequency of 9.6 * 10(4) h(-1)
      (0.125 mol% catalyst, 100% MMA conversion in 30 s, M(n) = 2.12 * 10(5) g mol(-1),
      PDI = 1.34). The polymers produced by LPs at RT are typically atactic
      (P(gamma)MMBL with ~47% mr) or syndio-rich (PMMA with ~70-75% rr), but highly
      syndiotactic PMMA with rr ~91% can be produced by chiral or achiral LPs at -78 
      degrees C. Mechanistic studies have identified and structurally characterized
      zwitterionic phosphonium and imidazolium enolaluminates as the active species of
      the current LPP system, which are formed by the reaction of the
      monomer.Al(C(6)F(5))(3) adduct with P(t)Bu(3) and NHC bases, respectively.
      Kinetic studies have revealed that the MMA polymerization by the
      (t)Bu(3)P/Al(C(6)F(5))(3) pair is zero-order in monomer concentration after an
      initial induction period, and the polymerization is significantly catalyzed by
      the LA, thus pointing to a bimetallic, activated monomer propagation mechanism.
      Computational study on the active species formation as well as the chain
      initiation and propagation events involved in the LPP of MMA with some of the
      most representative LPs has added our understanding of fundamental steps of LPP.
      The main difference between NHC and PR(3) bases is in the energetics of
      zwitterion formation, with the NHC-based zwitterions being remarkably more stable
      than the PR(3)-based zwitterions. Comparison of the monometallic and bimetallic
      mechanisms for MMA addition shows a clear preference for the bimetallic
      mechanism.

PMID- 22614677
TI  - Adolescent bulimia nervosa.
AB  - Onset of bulimia nervosa (BN) typically occurs in adolescence and is frequently
      accompanied by medical and psychiatric sequelae that may have detrimental effects
      on adolescent development. Potentially serious medical consequences and high
      comorbid rates of mood disorders and suicidality underscore the need for early
      recognition and effective treatments. Research among adolescents with BN has
      lagged behind that of adults, although evidence is accumulating to support the
      efficacy of family-based interventions and cognitive behavioral treatments that
      are adapted for use with adolescent populations. The aim of the current article
      is to provide an overview of recent research on epidemiology, risk factors,
      diagnostic issues, and treatment interventions focusing on adolescent BN, and to
      highlight areas for future research.

PMID- 22614679
TI  - An aptamer-based fluorescence biosensor for multiplex detection using unmodified
      gold nanoparticles.
AB  - A novel aptamer-based fluorescence biosensor for multiplex detection using
      unmodified AuNPs is developed to detect adenosine, thrombin and cocaine. Besides,
      this strategy can be applied to detect other small molecule substances.

PMID- 22614681
TI  - Evaluation of histological regression grading systems in the neoadjuvant therapy
      of rectal cancer: do they have prognostic impact?
AB  - PURPOSE: Neoadjuvant treatment options have been developed to improve survival of
      patients with locally advanced rectal cancer. As only patients with a major
      histopatholocial response benefit from this preoperative therapy, several tumor
      regression grading systems have been developed. However, currently no accepted
      comprehensive grading system for clinical use is available. Therefore, we studied
      the impact of four histological regression grading systems in the neoadjuvant
      therapy of rectal cancer. METHODS: In this retrospective study, 85 patients with
      locally advanced rectal cancer were included. All patients received a neoadjuvant
      radiochemotherapy followed by surgical resection. The histological regression
      grading was evaluated using four classification systems: (1) grading system by
      the Japanese society of colorectal cancer, (2) grading system by Junker-Muller,
      (3) grading system by Dworak, (4) Cologne grading system. The four classification
      systems were analyzed for their prognostic impact. RESULTS: The following
      significant correlations were detected between the four classification systems
      and the ypTNM categories: (1) patients with a ypT3/4 category had significantly
      more often a worse histopathologic response in all four grading systems (p =
      0.001); (2) a ypN0 category was significantly correlated with good
      histopathologic response only in the Cologne grading system; (3) in the Junker
      Muller and Dworak grading systems, a ypM0 category was significantly correlated
      with a good histopathologic response (p = 0.046; p = 0.03). However, none of the
      used classification systems had a prognostic impact on survival. CONCLUSIONS:
      Currently, none of the analyzed histological regression grading systems is
      effective for clinical use.

PMID- 22614682
TI  - Normative values in anorectal manometry using microtip technology: a cohort study
      in 172 subjects.
AB  - PURPOSE: The aims of this study were to obtain normative values in
      resting/squeeze pressure and surface electromyography (s-EMG) in anorectal
      manometry using microtip technology and to determine the relationship between
      objective measurable values, gender and age in a cohort with no anorectal
      disorders. METHODS: One hundred seventy-two white central European subjects (106
      males/66 females) were recruited prior to left colonic or upper rectal surgery
      and studied by anorectal rapid pull-through manometry with a microtip transducer
      system and endoanal s-EMG using a bipolar plug electrode. s-EMG patterns were
      determined as plateau, peak and decrease by a blinded co-investigator. Objective
      measurable sphincter pressures and s-EMG values were correlated with gender, age
      and s-EMG patterns. RESULTS: Squeeze pressure, voluntary pressure as well as s
      EMG amplitude and its area under the curve were significantly lower in women
      compared to men (p < 0.001 each), whereas resting pressure showed no gender
      differences. s-EMG patterns were strongly influenced by gender. Male patients
      showed significantly more plateau pattern whereas peak pattern was significantly
      more often in women. In both genders, the peak pattern was associated with
      significant higher squeeze pressures. In all measurements, we found considerable
      inter-individual variations being higher in elder patients. There was no
      manometric parameter correlating with age. CONCLUSIONS: Gender is the strongest
      factor influencing objective measurable manometric data for healthy men and
      women. There are significant gender differences concerning squeeze patterns. All
      manometric values should be interpreted in the context of gender and of
      methodology used. Large prospective cohort studies matched for gender are
      necessary to clarify the effect of ageing on anal sphincter strength.

PMID- 22614680
TI  - Environmental factors in causing human cancers: emphasis on tumorigenesis.
AB  - The environment and dietary factors play an essential role in the etiology of
      cancer. Environmental component is implicated in ~80 % of all cancers; however,
      the causes for certain cancers are still unknown. The potential players
      associated with various cancers include chemicals, heavy metals, diet, radiation,
      and smoking. Lifestyle habits such as smoking and alcohol consumption, exposure
      to certain chemicals (e.g., polycyclic aromatic hydrocarbons, organochlorines),
      metals and pesticides also pose risk in causing human cancers. Several studies
      indicated a strong association of lung cancer with the exposure to tobacco
      products and asbestos. The contribution of excessive sunlight, radiation,
      occupational exposure (e.g., painting, coal, and certain metals) is also well
      established in cancer. Smoking, excessive alcohol intake, consumption of an
      unhealthy diet, and lack of physical activity can act as risk factors for cancer
      and also impact the prognosis. Even though the environmental disposition is
      linked to cancer, the level and duration of carcinogen-exposure and associated
      cellular and biochemical aspects determine the actual risk. Modulations in
      metabolism and DNA adduct formation are considered central mechanisms in
      environmental carcinogenesis. This review describes the major environmental
      contributors in causing cancer with an emphasis on molecular aspects associated
      with environmental disposition in carcinogenesis.

PMID- 22614683
TI  - Weight loss and its relation to fat aspiration yields in liposuction: a survey in
      48 patients.
AB  - BACKGROUND: Liposuction surgeons often observe individually fluctuating amounts
      of aspirated fat. In patients with sagging skin due to previous weight loss there
      is a tendency of decreased fat aspiration volumes. OBJECTIVE: To study the
      influence of weight loss on fat aspiration volumes in a series of 48 patients.
      METHODS: We matched individuals of the same gender, but with a different weight
      history from a vast number of patients who had undergone liposuction surgery. The
      aspirated fat to wetting solution ratio (FWR) of the circumferential abdominal
      region was evaluated in three groups: A - patients with no weight loss (n = 16; 8
      males/ 8 females), B - patients with a history of moderate weight loss (weight
      loss 5-10% of body weight; n = 16; 8 males/8 females), and C - patients who had a
      massive weight loss prior to surgery (weight loss exceeding 15% of body weight; n
      = 16; 8 males/8 females). RESULTS: The aspirated FWR was 3.4 +/- 0.5, 1.0 +/- 0.3
      and 0.4 +/- 0.2 in groups A, B and C, respectively. The differences between the
      groups were statistically significant (p < 0.001). CONCLUSION: There are
      significant differences in patients with moderate or massive weight loss in
      regard to fat aspiration volumes compared to patients without prior weight loss.
      These findings point to the importance of a weight loss history prior to surgery.
      Regardless of lower fat aspiration yields in patients with massive weight loss,
      good results are still achievable. This is not only due to volume reduction but
      to skin tightening.

PMID- 22614685
TI  - DNA-based catalytic enantioselective intermolecular oxa-Michael addition
      reactions.
AB  - Using the DNA-based catalysis concept, a novel Cu(ii) catalyzed enantioselective
      oxa-Michael addition of alcohols to enones is reported. Enantioselectivities of
      up to 86% were obtained. The presence of water is important for the reactivity,
      possibly by reverting unwanted side reactions such as 1,2-additions.

PMID- 22614687
TI  - Pedicle subtraction osteotomy for postoperative flat back and sagittal imbalance.

PMID- 22614689
TI  - Percutaneous multilevel reconstruction in revision surgery.

PMID- 22614690
TI  - Transition anomalies at the lumbosacral junctions.

PMID- 22614688
TI  - Improving safety in spinal deformity surgery: advances in navigation and
      neurologic monitoring.
AB  - INTRODUCTION: The treatment of spinal deformities has rapidly changed during the
      past decade. The advent of new surgical techniques, particularly thoracic pedicle
      screws and spinal osteotomies, allow more aggressive deformity correction, and
      require an increased focus on safety. MATERIALS AND METHODS: Review of the
      navigation systems and neuromonitoring techniques currently available.
      CONCLUSION: Navigation systems today are where intraoperative neuromonitoring was
      20 years ago: new, under investigation, not widely accepted, with concerns for
      cost, safety and efficiency. Navigation enhances the accuracy of pedicle screws
      placement in deformed spines, reducing the rate of misplaced screws and potential
      complications. With further use and investigation, navigation, like
      neuromonitoring, will soon become standard at major spine centers throughout the
      world.

PMID- 22614691
TI  - Percutaneous scoliosis surgery.

PMID- 22614692
TI  - Joint-structured-sparsity-based classification for multiple-measurement transient
      acoustic signals.
AB  - This paper investigates the joint-structured-sparsity-based methods for transient
      acoustic signal classification with multiple measurements. By joint structured
      sparsity, we not only use the sparsity prior for each measurement but we also
      exploit the structural information across the sparse representation vectors of
      multiple measurements. Several different sparse prior models are investigated in
      this paper to exploit the correlations among the multiple measurements with the
      notion of the joint structured sparsity for improving the classification
      accuracy. Specifically, we propose models with the joint structured sparsity
      under different assumptions: same sparse code model, common sparse pattern model,
      and a newly proposed joint dynamic sparse model. For the joint dynamic sparse
      model, we also develop an efficient greedy algorithm to solve it. Extensive
      experiments are carried out on real acoustic data sets, and the results are
      compared with the conventional discriminative classifiers in order to verify the
      effectiveness of the proposed method.

PMID- 22614693
TI  - Effect of self-demodulation on the subharmonic response of contrast agent
      microbubbles.
AB  - Subharmonic (SH) emission from the ultrasound contrast agent (UCA) is of interest
      since it is produced only by the UCA and not by tissue, opposite to harmonic
      imaging modes where both tissue and microbubble show harmonics. In this work, the
      use of the self-demodulation (S-D) signal as a means of microbubble excitation at
      the SH frequency to enhance the SH emission of UCA is studied. The S-D wave is a
      low-frequency signal produced by the weak nonlinear propagation of an ultrasound
      wave. It is proportional to the second time derivative of the squared envelope of
      the transmitted signal. A diluted population of BR14 UCA (Bracco Research SA,
      Geneva, Switzerland) was insonified by a 10 MHz transducer focused at 76 mm
      firing bursts with different envelopes, durations and peak pressure amplitudes.
      The center frequency of the S-D signal changes from low frequencies (around 0.5
      MHz) toward the transmitted frequency (10 MHz) by modifying the envelope function
      from gaussian to rectangular. For 6 and 20 transmitted cycles, the SH response is
      enhanced up to 25 and 22 dB, respectively, when using a rectangular envelope
      instead of a gaussian one. The experimental results are confirmed by the
      numerical simulation. The effects of the excitation duration and pressure
      amplitude are also studied. This study shows that a suitable design of the
      envelope of the transmit excitation to generate a S-D signal at the SH frequency
      can enhance the SH emission of UCA, and the SH imaging is feasible at high
      frequencies with a shorter transmit burst (six-cycle) and low acoustic pressure
      (~100 KPa).

PMID- 22614694
TI  - Cytochrome P450 2E1 variable number tandem repeat polymorphisms and health risks:
      a genotype-phenotype study in cancers associated with drinking and/or smoking.
AB  - Cytochrome P450 2E1 (CYP2E1) is one of the main enzymes involved in the oxidation
      of ethanol and in the transformation of a number of potentially dangerous
      compounds. It has various polymorphic sites, one of which is a variable number
      tandem repeat (VNTR) polymorphism previously described in the 5'-flanking region.
      The aim of this study was to investigate the genotype-phenotype association
      between CYP2E1 VNTR polymorphisms and risky health habits in healthy subjects and
      to analyze the associations between these polymorphisms with drinking- and/or
      smoking-related cancers. We analyzed 166 healthy subjects by genotyping for the
      CYP2E1 VNTR polymorphism associated with drinking and/or smoking habits by the
      more sensitive restriction fragment length polymorphism-polymerase chain reaction
      (RFLP-PCR) method, using the NlaIV restriction enzyme. Sixty cases of pancreatic
      adenocarcinoma (PA) and 66 with hepatocellular carcinoma (HCC), were also
      genotyped. Statistical analysis was carried out to investigate the genotype
      phenotype associations and to compare certain genotypes and cancer. We found 7
      genotypes both in the healthy subjects and patients. The A1/A1 genotype was
      observed to be mainly associated with non-drinkers and -smokers (87.5 and 75.0%,
      respectively); moreover it was never found in the PA or HCC patients. Conversely,
      a weak association between A2/A3 with smokers (45.8%) and A4/A4 with drinkers
      (53.9%) was detected. In addition, the A4/A4 genotype was found to be
      significantly associated to PA [odds ratio (OR)=3.25; 95% confidence interval
      (CI) 1.21-7.50]. Our data demonstrate that certain CYP2E1 VNTR genotypes are
      associated with drinking and/or smoking habits; consequently, they may contribute
      either to the decreased or increased risk of developing drinking- and/or smoking
      related cancers. In particular, we hypothesize that the A1/A1 VNTR genotype may
      have a protective role against drinking- and/or smoking-related cancers, and that
      A4/A4 may be a high-risk genotype during the early stages of cancer.

PMID- 22614695
TI  - Fibroblast activation protein regulates tumor-associated fibroblasts and
      epithelial ovarian cancer cells.
AB  - The fibroblast activation protein (FAP) is a cell surface serine protease which
      has emerged as a specific marker of tumor-associated fibroblasts (TAFs). FAP has
      been shown to have both in vitro dipeptidyl peptidase and collagenase activity.
      However, the biological function of FAP in the tumor microenvironment is largely
      unknown. In this study, we first show that TAFs isolated from ovarian cancer
      samples have the characteristics of stem cells. To explore the functional role of
      FAP, the protein was silenced by siRNA lentiviral vector transfection. FAP
      silencing inhibited the growth of TAFs in vitro, accompanied with cell cycle
      arrest at the G2 and S phase in TAFs. FAP silencing also reduced the stem cell
      marker gene expression in TAFs. SKOV3 cells do not express FAP. Although FAP
      silenced SKOV3 cells induced ovarian tumors, the rate of tumor growth was
      significantly decreased, as shown in the xenograft mouse model. TAF phenotypes in
      the xenograft tumor tissues were further assayed by immunohistochemistry. The
      expression of TAF markers, including fibroblast-specific protein, FAP, smooth
      muscle actin, desmin, vascular endothelial growth factor and fibroblast growth
      factor was decreased in the tumor stroma induced by FAP-silenced SKOV3 cells. In
      conclusion, FAP is an important regulator of the microenvironment in tumor
      formation and targeting FAP is a potential therapeutic strategy to combat ovarian
      cancer.

PMID- 22614696
TI  - Developmental alcohol-specific parenting profiles in adolescence and their
      relationships with adolescents' alcohol use.
AB  - Previous studies on general parenting have demonstrated the relevance of strict
      parenting within a supportive social context for a variety of adolescent
      behaviors, such as alcohol use. Yet, alcohol-specific parenting practices are
      generally examined as separate predictors of adolescents' drinking behavior. The
      present study examined different developmental profiles of alcohol-specific
      parenting (rule-setting, quality and frequency of communication about alcohol
      use) and how these patterns relate to the initiation and growth of adolescents'
      drinking. A longitudinal sample of 883 adolescents (47 % female) including four
      measurements (between ages 12 and 16) was used. Latent class growth analysis
      revealed that five classes of parenting could be distinguished. Communication
      about alcohol appeared to be fairly stable over time in all parenting classes,
      whereas the level of rule-setting declined in all subgroups of parents as
      adolescents grow older. Strict rule-setting in combination with a high quality
      and frequency of communication was associated with the lowest amount of drinking;
      parents scoring low on all these behaviors show to be related to the highest
      amount of drinking. This study showed that alcohol-specific rule-setting is most
      effective when it coincides with a good quality and frequency of communication
      about alcohol use. This indicates that alcohol-specific parenting behaviors
      should be taken into account as an alcohol-specific parenting context, rather
      than single parenting practices. Therefore, parent-based alcohol interventions
      should not only encourage strict rule setting, the way parents communicate with
      their child about alcohol is also of major importance.

PMID- 22614698
TI  - Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) as
      neoadjuvant chemotherapy for patients with muscle-invasive transitional cell
      carcinoma of the bladder.
AB  - BACKGROUND: Meta-analysis data demonstrate a 5% absolute survival benefit for
      neoadjuvant chemotherapy (NAC) using cisplatin-based combination regimens in the
      radical treatment of muscle-invasive bladder cancer (MIBC). However, there are no
      randomized, controlled trial data on the optimum regimen. Accelerated
      methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) is a dose-intense
      regimen that has the potential to minimize delays to definitive, potentially
      curative therapy. A retrospective analysis is presented of the efficacy and
      toxicity of AMVAC as NAC in patients with MIBC and its impact on the patient
      pathway. METHODS: Eighty consecutive patients with MIBC were treated with AMVAC
      as NAC by 2 UK multidisciplinary uro-oncology teams. Three or 4 cycles of AMVAC
      (methotrexate 30 mg/m(2) , vinblastine 3 mg/m(2) , doxorubicin 30 mg/m(2) , and
      cisplatin 70 mg/m(2) ) were given at 2-week intervals, with granulocyte colony
      stimulating factor support, prior to either radical surgery or radical
      radiotherapy. RESULTS: All planned cycles of chemotherapy were completed, without
      dose reduction or delay in 84% of patients. All 80 patients subsequently received
      their planned definitive therapy. Grade 3/4 toxicities were seen in 26% of the
      42% of patients for whom toxicity data are available, including 12% grade 3/4
      neutropenia. Pathological complete response to AMVAC was seen in 43% of 60
      surgical patients. Objective radiological local response was seen in 83% of 57
      evaluable patients. Two-year disease-free and overall survival were 65% and 77%,
      respectively. CONCLUSIONS: AMVAC is safe and appears to be a well-tolerated and
      effective NAC regimen for MIBC. It minimizes delays to definitive treatment and
      produces excellent pathological and radiological response rates. It is an
      appropriate comparator for future randomized trials.

PMID- 22614699
TI  - Non-obstructive membranes of the left atrial appendage.
AB  - The left atrial appendage (LAA) is a blind-ending, complex structure distinct
      from the body of the left atrium and is sometimes regarded as a minor extension
      of the atrium. However, it should routinely be analysed as part of a 
      transoesophageal echocardiographic examination. In this study we describe the
      presence of a non-obstructive membrane traversing the cavity of the LAA, found
      incidentally on transoesophageal echocardiography.

PMID- 22614697
TI  - Inflamed tumor-associated adipose tissue is a depot for macrophages that
      stimulate tumor growth and angiogenesis.
AB  - Tumor-associated stroma is typified by a persistent, non-resolving inflammatory
      response that enhances tumor angiogenesis, growth and metastasis. Inflammation in
      tumors is instigated by heterotypic interactions between malignant tumor cells,
      vascular endothelium, fibroblasts, immune and inflammatory cells. We found that
      tumor-associated adipocytes also contribute to inflammation. We have analyzed
      peritumoral adipose tissue in a syngeneic mouse melanoma model. Compared to
      control adipose tissue, adipose tissue juxtaposed to implanted tumors exhibited
      reduced adipocyte size, extensive fibrosis, increased angiogenesis and a dense
      macrophage infiltrate. A mouse cytokine protein array revealed up-regulation of
      inflammatory mediators including IL-6, CXCL1, MCP-1, MIP-2 and TIMP-1 in
      peritumoral versus counterpart adipose tissues. CD11b(+) macrophages contributed
      strongly to the inflammatory activity. These macrophages were isolated from
      peritumoral adipose tissue and found to over-express ARG1, NOS2, CD301, CD163,
      MCP-1 and VEGF, which are indicative of both M1 and M2 polarization. Tumors
      implanted at a site distant from subcutaneous, anterior adipose tissue were
      strongly growth-delayed, had fewer blood vessels and were less populated by
      CD11b(+) macrophages. In contrast to normal adipose tissue, micro-dissected
      peritumoral adipose tissue explants launched numerous vascular sprouts when
      cultured in an ex vivo model. Thus, inflamed tumor-associated adipose tissue
      fuels the growth of malignant cells by acting as a proximate source for vascular
      endothelium and activated pro-inflammatory cells, in particular macrophages.

PMID- 22614700
TI  - Aortic dissection, a complication during successful angioplasty of chronic total
      occlusion of the right coronary artery, was treated conservatively.
AB  - Aortic dissection is an uncommon but potentially lethal complication that can
      occur during the engagement of a guiding catheter. We report a case of a  59-year
      old woman with acute aortic dissection due to percutaneous coronary intervention.
      This resulted in a retrograde extension of the dissection into the proximal part
      of the ascending aorta. With haemodynamic stability, we decided to treat the
      aortic dissection medically. As a result, a complete resolution of the aortic
      dissection was documented by coronary angiography and the follow-up computed
      tomography scan.

PMID- 22614701
TI  - Mobile atheromatous plaque of the aortic arch diagnosed by transthoracic
      echocardiography prior to coronary artery bypass surgery. Which one would you
      choose: scepticism or wishful thinking?
AB  - A routine pre-operative chest X-ray of a patient admitted to our institution for
      an elective coronary artery bypass operation revealed a mildly dilated
      mediastinal silhouette, which led the cardiovascular surgery resident to schedule
      emergency transthoracic echocardiography (TTE), with a special note asking for
      detailed evaluation of the ascending aorta and aortic arch. TTE revealed a mobile
      atheroma at the aortic arch, which obliged the cardiac surgery team to modify
      their strategy to combined hemi-arcus aortae replacement and coronary artery
      bypass grafting (CABG). Although with transoesophageal echocardiography (TEE) a
      small portion of the ascending aorta may be obscured by the trachea, TEE provides
      higher resolution images than TTE. Therefore one can conclude that TEE is the
      imaging modality of choice for detecting aortic atheromatous plaques but in
      patients with low risk for stroke and aortic atheromas, a detailed TTE may be
      sufficient for the pre-operative assessment.

PMID- 22614702
TI  - Successful stenting of catheter-induced unprotected left main coronary artery
      dissection.
AB  - Catheter-induced left main coronary artery (LMCA) dissection is a dramatic,
      although uncommon complication of diagnostic coronary angiography and requires
      prompt treatment. We describe a case of iatrogenic occlusive dissection of the
      LMCA during coronary angiography, treated by subsequent percutaneous
      recanalisation.

PMID- 22614703
TI  - New images in carcinoid heart disease.
AB  - Echocardiography was the main imaging technique in the diagnosis and follow up of
      carcinoid heart disease but in the last decade magnetic resonance imaging  (MRI)
      has evolved into a new diagnostic modality. Most of the reported MRI features
      were similar to those observed by echocardiography - tricuspid and/or pulmonary
      valve thickening and immobility with consequent valvular dysfunction and right
      heart enlargement. To our knowledge, this is the first report describing
      endocardial enhancement of the right cardiac chambers, tricuspid valve and
      subvalvular apparatus, which corresponds with histologically seen fibrous
      carcinoid plaques.

PMID- 22614705
TI  - Activated fluid transport regulates bacterial-epithelial interactions and
      significantly shifts the murine colonic microbiome.
AB  - Within the intestinal mucosa, epithelial cells serve multiple functions to
      partition the lumen from the lamina propria. As part of their natural function,
      intestinal epithelial cells actively transport electrolytes with passive water
      movement as a mechanism for mucosal hydration. Here, we hypothesized that
      electrogenic Cl(-) secretion, and associated mucosal hydration, influences
      bacterial-epithelial interactions and significantly influences the composition of
      the intestinal microbiota. An initial screen of different epithelial
      secretagogues identified lubiprostone as the most potent agonist for which to
      define these principles. In in vitro studies using cultured T84 cells,
      lubiprostone decreased E. coli translocation in a concentration-dependent manner
      (p < 0.001) and decreased S. typhimurium internalization and translocation by as
      much as 71 +/- 6% (p < 0.01). Such decreases in bacterial translocation were
      abolished by inhibition of electrogenic Cl(-) secretion and water transport using
      the Na/K/Cl(-) antagonist bumetanide (p < 0.01). Extensions of these findings to
      microbiome analysis in vivo revealed that lubiprostone delivered orally to mice
      fundamentally shifted the intestinal microbiota, with notable changes within the
      Firmicutes and Bacteroidetes phyla of resident colonic bacteria. Such findings
      document a previously unappreciated role for epithelial Cl(-) secretion and water
      transport in influencing bacterial-epithelial interactions and suggest that
      active mucosal hydration functions as a primitive innate epithelial defense
      mechanism.

PMID- 22614706
TI  - Diffusion tensor imaging shows structural remodeling of stroke mirror region:
      results from a pilot study.
AB  - BACKGROUND: The role of the non-injured hemisphere in stroke recovery is poorly
      understood. In this pilot study, we sought to explore the presence of structural
      changes detectable by diffusion tensor imaging (DTI) in the contralesional
      hemispheres of patients who recovered well from ischemic stroke. METHODS: We
      analyzed serial DTI data from 16 stroke patients who had moderate initial
      neurological deficits (NIHSS scores 3-12) and good functional outcome at 3-6
      months (NIHSS score 0 or modified Rankin Score <=1). We segmented the brain
      tissue in gray and white matter (GM and WM) and measured the apparent diffusion
      coefficient (ADC) and fractional anisotropy in the infarct, in the contralesional
      infarct mirror region as well as in concentrically expanding regions around them.
      RESULTS: We found that GM and WM ADC significantly increased in the infarct
      region (p < 0.01) from acute to chronic time points, whereas in the infarct
      mirror region, GM and WM ADC increased (p < 0.01) and WM fractional anisotropy
      decreased (p < 0.05). No significant changes were detected in other regions.
      CONCLUSION: DTI-based metrics are sensitive to regional structural changes in the
      contralesional hemisphere during stroke recovery. Prospective studies in larger
      cohorts with varying levels of recovery are needed to confirm our findings.

PMID- 22614704
TI  - Fimbriation and curliation in Escherichia coli O157:H7: a paradigm of intestinal
      and environmental colonization.
AB  - Shiga toxin-producing Escherichia coli (STEC) serotypes, particularly E. coli
      O157:H7, possess a variety of fimbrial and afimbrial adhesins which have emerged
      as important contributors to intestinal colonization. E. coli O157:H7 possesses
      two chromosomal operons encoding long polar fimbriae (Lpf), which have been found
      to influence adherence in vitro and colonization in vivo. In a recent Infection
      and Immunity paper, we further explored the role of Lpf in E. coli O157:H7
      intestinal colonization by using the infant rabbit model of STEC infection. We
      found that an E. coli O157:H7 Lpf-deficient mutant was outcompeted in the rabbit
      intestine by its parental strain, which may suggest that Lpf contributes to
      colonization. In contrast, the Lpf-deficient mutant showed an increased adherence
      to cultured intestinal epithelial cells, and we discovered that this strain
      overexpressed curli fibers. In this addendum article, we provide a continued
      perspective on the predicted roles of Lpf and curli, both in vivo and in vitro.

PMID- 22614707
TI  - Analysis of egg-based model wall paintings by use of an innovative combined dot
      ELISA and UPLC-based approach.
AB  - The chemical analysis of egg-based wall paintings-the mezzo fresco technique-is
      an interesting topic in the characterisation of organic binders. A revised
      procedure for a dot-enzyme-linked immunosorbent assay (dot-ELISA) able to detect
      protein components of egg-based wall paintings is reported. In the new dot-ELISA
      procedure we succeeded in maximizing the staining colour by adjusting the
      temperature during the staining reaction. Quantification of the colour intensity
      by visible reflectance spectroscopy resulted in a straight line plot of protein
      concentration against reflectance in the wavelength range 380-780 nm. The
      modified dot-ELISA procedure is proposed as a semi-quantitative analytical method
      for characterisation of protein binders in egg-based paintings. To evaluate its
      performance, the method was first applied to standard samples (ovalbumin, whole
      egg, egg white), then to model specimens, and finally to real samples (Giotto's
      wall paintings). Moreover, amino acid analysis performed by innovative ultra
      performance liquid chromatography was applied both to standards and to model
      samples and the results were compared with those from the dot-ELISA tests. In
      particular, after protein hydrolysis (24 h, 114  degrees C, 6 mol L(-1) HCl) of
      the samples, amino acid derivatization by use of 6-aminoquinolyl-N
      hydroxysuccinimidyl carbamate enabled reproducible analysis of amino acids. This
      UPLC amino acid analysis was rapid and reproducible and was applied for the first
      time to egg-based paintings. Because the painting technique involved the use of
      egg-based tempera on fresh lime-based mortar, the study enabled investigation of
      the effect of the alkaline environment on egg-protein detection by both methods.

PMID- 22614709
TI  - Gold-nanosphere formation using food sample endogenous polyphenols for in-vitro
      assessment of antioxidant capacity.
AB  - In this work it was demonstrated that sample endogenous polyphenols are
      selectively driving the gold-nanoparticle (AuNPs)-formation process when
      representative food samples were used as natural sources of reducing compounds.
      The process of AuNPs formation was characterized by UV-visible spectroscopy and
      was described by a sigmoidal curve (R (2) >= 0.990) which gave information about
      the polyphenol concentration at which the localized surface plasmon resonance
      (LSPR) absorption reached its half-value, X (c) (50) , and about AuNPs production
      per polyphenol concentration unit, K (AuNPs). The behavior of phenolic acids was
      different, with lower X (c) (50) and higher K (AuNPs) values than flavonoids. For
      the food samples tea, apple, pear, wine, and honey X (c) (50) values were 0.22,
      7.3, 11.5, 20.4, 30.3, and 53.5 (mg mL(-1)) and K (AuNPs) values were 28.7, 0.70,
      0.60, 0.20, 0.14, and 0.10 (mg(-1) mL), respectively. Excellent correlation
      between K (AuNPs) and total phenolics (TP) was obtained (r = 0.98, p-value <
      0.05), implying K (AuNPs) is a novel marker for evaluation of food sample
      antioxidant capacity in vitro. The K (AuNPs) values of samples indicated their
      antioxidant capacity was in the order: tea > apple > pear > wine > honey. The
      reproducibility of the AuNPs formation approach was excellent, not only for
      polyphenol standards (RSD < 6 % for X (c) (50) and RSD < 11 % for K (AuNPs)) but
      also for food samples (RSD < 9 % for X (c) (50) and RSD < 15 % for K (AuNPs)).
      Transmission electronic microscopy (TEM) enabled confirmation of the formation of
      stabilized Au-nanospheres from endogenous polyphenols with very well-defined
      sizes under 20 nm diameter for all the food samples investigated.

PMID- 22614711
TI  - Incidence of BRAF p.Val600Glu and p.Val600Lys mutations in a consecutive series
      of 183 metastatic melanoma patients from a high incidence region.
AB  - AIM: Approximately 40-60% of melanomas from Caucasian populations carry
      activating mutations in the BRAF oncogene, with the most common being the
      p.Val600Glu (V600E) hotspot mutation in exon 15. The aim of the present study was
      to investigate the frequency of the less common p.Val600Lys (V600K) mutation in
      metastatic melanoma from a high incidence region. METHOD: Dideoxy sequencing and
      fluorescent single strand conformation analysis were used to screen for mutations
      in exon 15 of BRAF in 183 cases of metastatic melanoma. RESULTS: The overall
      incidence of BRAF mutation (89/183, 49%) was very similar to other large studies
      of Caucasian populations. However, the frequency of the p.Val600Lys mutation was
      higher than in most other studies and comprised almost one-third of all BRAF
      mutations in our cohort (27/89, 30%). CONCLUSION: BRAF p.Val600Lys mutations were
      present at a relatively high frequency in this cohort of metastatic melanoma
      patients (27/183, 15%). Assays used to screen for BRAF mutations in the clinic
      should be robust enough to detect the p.Val600Lys mutation, as this may have
      therapeutic implications.

PMID- 22614710
TI  - High-sensitivity C-reactive protein as a marker of cardiovascular risk in
      systemic lupus erythematosus.

PMID- 22614716
TI  - Diabetes: early initiation of intensive therapy might benefit children with type
      2 diabetes mellitus.

PMID- 22614712
TI  - Selenium enhances the efficacy of Radachlorin mediated-photodynamic therapy in TC
      1 tumor development.
AB  - Selenium, an essential trace element possessing anti-carcinogenic properties, can
      induce apoptosis in cancer cells. Our goal was to investigate the enhanced
      antitumor effects of photodynamic therapy (PDT) plus selenium in TC-1 tumor cells
      and implanted mice. Cell viability was evaluated at various time intervals after
      PDT treatment and/or selenium by methyl thiazolyl tetrazolium (MTT) assay. When
      only PDT treatment was administered to TC-1 tumor cells, TC-1 cell growth
      recovered over time. On the other hand, co-treatment of PDT and selenium extended
      the inhibition time of tumor cell growth. Co-treatment of PDT and selenium showed
      serious morphological changes in TC-1 cells and induced a more apoptotic
      population by FACS analysis. By signal transduction pathway SuperArray analysis,
      genes closely involved in the NFkappaB, p53 and phopholipase C pathways, such as
      VCAM1, MDM2 and FOS, were significantly downregulated at least 10-fold in TC-1
      cells following PDT and selenium cotreatment. In an in vivo study, tumor-bearing
      mice were intravenously injected with Radachlorin 3 h before irradiation with 300
      J/cm2 of light. Selenium was administered daily for 20 days. Combination therapy
      against the mouse tumors generated by TC-1 cells was more effective than PDT or
      selenium alone. These data suggest that selenium plus PDT can induce a
      significant tumor suppression response compared with PDT alone. Additionally, it
      can be an effective anticancer therapy strategy.

PMID- 22614717
TI  - Adrenal gland: adrenocortical carcinoma-first RCT.

PMID- 22614718
TI  - Nutrition: breast is best for avoiding obesity.

PMID- 22614719
TI  - Recent advances in fixation of the craniomaxillofacial skeleton.
AB  - PURPOSE OF REVIEW: Fixation of the craniomaxillofacial skeleton is an evolving
      aspect for facial plastic, oral and maxillofacial, and plastic surgery. This
      review looks at the recent advances that aid in reduction and fixation of the
      craniomaxillofacial skeleton. RECENT FINDINGS: More surgeons are using resorbable
      plates for craniomaxillofacial fixation. A single miniplate on the inferior
      border of the mandible may be sufficient to reduce and fixate an angle fracture.
      Percutaneous K-wires may assist in plating angle fractures. Intraoperative
      computed tomography (CT) may prove to be useful for assessing reduction and
      fixation. SUMMARY: Resorbable plates are becoming increasingly popular in
      orthognathic surgery and facial trauma surgery. There are newer operative
      techniques for fixating the angle of the mandible. Also, the utilization of the
      intraoperative CT provides immediate feedback for accurate reduction and
      fixation. Prebent surgical plates save operative time, decrease errors, and
      provide more accurate fixation.

PMID- 22614720
TI  - Caffeine in hot drinks elicits cephalic phase responses involving cardiac
      activity.
AB  - Caffeine stimulates both oropharyngeal and gut bitter taste receptors (hTAS2Rs)
      and so has the potential to elicit reflex autonomic responses. Coffee containing
      130 mg caffeine has been reported to increase heart rate for 30 min post
      ingestion. Whereas added-caffeine, in doses of 25 to 200 mg, ingested with
      decaffeinated coffee/tea decreases heart rate 10 to 30 min post-ingestion. This
      study aimed to clarify caffeine's chemosensory impact. Double-espresso coffees
      were compared to a placebo-control capsule in a double-blind between-measures
      design. Coffees tested were regular coffee (130 mg caffeine) and decaffeinated
      coffee with added-caffeine (0, 67 and 134 mg). Cardiovascular measures from three
      post-ingestion phases: 1) 0 to 5; 2) 10 to 15; and 3) 25 to 30 min; were compared
      to pre-ingestion measures. Participants comprised 11 women in the control group
      and 10 women in the test group. Decaffeinated coffee elicited no changes.
      Decaffeinated coffee with 67 mg caffeine: decreased dp/dt in Phase 1.
      Decaffeinated coffee with 134 mg caffeine: increased heart rate in Phases 1 and
      2; decreased spontaneous baroreflex sensitivity in Phase 1; and increased
      diastolic pressure in Phases 2 and 3. Regular coffee: increased heart rate in
      Phases 1 and 2; decreased dp/dt in all phases; and decreased systolic pressure in
      Phase 1. Caffeine is the substance in regular coffee which elicits chemosensory
      autonomic reflex responses, which involves heart activity and the baroreflex.
      Compared to the caffeine in regular coffee, added-caffeine elicits somewhat
      different chemosensory responses including a more pronounced pressor effect and
      resetting of the baroreflex. Caffeine in commonly consumed amounts, as well as
      modulating body processes by blocking adenosine receptors, can elicit reflex
      autonomic responses during the ingestion of caffeinated drinks. It is plausible
      that caffeine stimulates hTAS2Rs, during the ingestion of coffee, eliciting
      cephalic phase responses. These cephalic phase responses likely result from vagal
      withdrawal and it is uncertain whether they enhance digestion or not.

PMID- 22614721
TI  - Belimumab and the clinical data.
AB  - Benlysta (belimumab) is a fully human recombinant monoclonal IgG antibody that
      neutralizes soluble B-lymphocyte stimulator and inhibits its biologic activity.
      Benlysta was recently approved by the US Food and Drug Administration to treat
      systemic lupus erythematosus (SLE). The current review discusses the data from
      the belimumab clinical trials and the role of this new medication in the
      treatment of SLE. We propose that Benlysta should be used in antinuclear antibody
      positive patients with active disease in whom the goal of therapy is to decrease
      SLE activity, reduce flares, and help lower background medications. With this
      being the first drug approved for treatment of SLE in 50 years, patients have
      more treatment options, while researchers have a greater understanding of SLE and
      clinical trial design in such a heterogeneous disease.

PMID- 22614722
TI  - Electrochemical tandem synthesis of oximes from alcohols using KNO3 as the
      nitrogen source, mediated by tin microspheres in aqueous medium.
AB  - Electrochemical oximation of alcohols was realized with KNO(3) as the nitrogen
      source mediated by tin microspheres.

PMID- 22614723
TI  - Optimizing medical data quality based on multiagent web service framework.
AB  - One of the most important issues in e-healthcare information systems is to
      optimize the medical data quality extracted from distributed and heterogeneous
      environments, which can extremely improve diagnostic and treatment decision
      making. This paper proposes a multiagent web service framework based on service
      oriented architecture for the optimization of medical data quality in the e
      healthcare information system. Based on the design of the multiagent web service
      framework, an evolutionary algorithm (EA) for the dynamic optimization of the
      medical data quality is proposed. The framework consists of two main components;
      first, an EA will be used to dynamically optimize the composition of medical
      processes into optimal task sequence according to specific quality attributes.
      Second, a multiagent framework will be proposed to discover, monitor, and report
      any inconstancy between the optimized task sequence and the actual medical
      records. To demonstrate the proposed framework, experimental results for a breast
      cancer case study are provided. Furthermore, to show the unique performance of
      our algorithm, a comparison with other works in the literature review will be
      presented.

PMID- 22614724
TI  - An incremental learning method based on probabilistic neural networks and
      adjustable fuzzy clustering for human activity recognition by using wearable
      sensors.
AB  - Human activity recognition by using wearable sensors has gained tremendous
      interest in recent years among a range of health-related areas. To automatically
      recognize various human activities from wearable sensor data, many classification
      methods have been tried in prior studies, but most of them lack the incremental
      learning abilities. In this study, an incremental learning method is proposed for
      sensor-based human activity recognition. The proposed method is designed based on
      probabilistic neural networks and an adjustable fuzzy clustering algorithm. The
      proposed method may achieve the following features. 1) It can easily learn
      additional information from new training data to improve the recognition
      accuracy. 2) It can freely add new activities to be detected, as well as remove
      existing activities. 3) The updating process from new training data does not
      require previously used training data. An experiment was performed to collect
      realistic wearable sensor data from a range of activities of daily life. The
      experimental results showed that the proposed method achieved a good tradeoff
      between incremental learning ability and the recognition accuracy. The
      experimental results from comparison with other classification methods
      demonstrated the effectiveness of the proposed method further.

PMID- 22614725
TI  - On the relevance of glycolysis process on brain gliomas.
AB  - The proposed analysis considers aspects of both statistical and biological
      validation of the glycolysis effect on brain gliomas, at both genomic and
      metabolic level. In particular, two independent datasets are analyzed in
      parallel, one engaging genomic (Microarray Expression) data and the other
      metabolomic (Magnetic Resonance Spectroscopy Imaging) data. The aim of this study
      is twofold. First to show that, apart from the already studied genes (markers),
      other genes such as those involved in the human cell glycolysis significantly
      contribute in gliomas discrimination. Second, to demonstrate how the glycolysis
      process can open new ways towards the design of patient-specific therapeutic
      protocols. The results of our analysis demonstrate that the combination of genes
      participating in the glycolytic process (ALDOA, ALDOC, ENO2, GAPDH, HK2, LDHA,
      LDHB, MDH1, PDHB, PFKM, PGI, PGK1, PGM1 and PKLR) with the already known tumor
      suppressors (PTEN, Rb, TP53), oncogenes (CDK4, EGFR, PDGF) and HIF-1, enhance the
      discrimination of low versus high-grade gliomas providing high prediction ability
      in a cross-validated framework. Following these results and supported by the
      biological effect of glycolytic genes on cancer cells, we address the study of
      glycolysis for the development of new treatment protocols. 

PMID- 22614727
TI  - Automated segmentation of the melanocytes in skin histopathological images.
AB  - In the diagnosis of skin melanoma by analyzing histopathological images, the
      detection of the melanocytes in the epidermis area is an important step. However,
      the detection of melanocytes in the epidermis area is dicult because other
      keratinocytes that are very similar to the melanocytes are also present. This
      paper proposes a novel computer-aided technique for segmentation of the
      melanocytes in the skin histopathological images. In order to reduce the local
      intensity variant, a mean-shift algorithm is applied for the initial segmentation
      of the image. A local region recursive segmentation algorithm is then proposed to
      filter out the candidate nuclei regions based on the domain prior knowledge. To
      distinguish the melanocytes from other keratinocytes in the epidermis area, a
      novel descriptor, named local double ellipse descriptor (LDED), is proposed to
      measure the local features of the candidate regions. The LDED uses two
      parameters: region ellipticity and local pattern characteristics to distinguish
      the melanocytes from the candidate nuclei regions. Experimental results on 28
      dierent histopathological images of skin tissue with dierent zooming factors show
      that the proposed technique provides a superior performance. 

PMID- 22614728
TI  - Learning new meanings for old words: effects of semantic relatedness.
AB  - Changes to our everyday activities mean that adult language users need to learn
      new meanings for previously unambiguous words. For example, we need to learn that
      a "tweet" is not only the sound a bird makes, but also a short message on a
      social networking site. In these experiments, adult participants learned new
      fictional meanings for words with a single dominant meaning (e.g., "ant") by
      reading paragraphs that described these novel meanings. Explicit recall of these
      meanings was significantly better when there was a strong semantic relationship
      between the novel meaning and the existing meaning. This relatedness effect
      emerged after relatively brief exposure to the meanings (experiment 1), but it
      persisted when training was extended across 7 days (experiment 2) and when
      semantically demanding tasks were used during this extended training (experiment
      3). A lexical decision task was used to assess the impact of learning on online
      recognition. In Experiment 3, participants responded more quickly to words whose
      new meaning was semantically related than to those with an unrelated meaning.
      This result is consistent with earlier studies showing an effect of meaning
      relatedness on lexical decision, and it indicates that these newly acquired
      meanings become integrated with participants' preexisting knowledge about the
      meanings of words.

PMID- 22614726
TI  - Cardiovascular genomics: a biomarker identification pipeline.
AB  - Genomic biomarkers are essential for understanding the underlying molecular basis
      of human diseases such as cardiovascular disease. In this review, we describe a
      biomarker identification pipeline for cardiovascular disease, which includes 1)
      high-throughput genomic data acquisition, 2) preprocessing and normalization of
      data, 3) exploratory analysis, 4) feature selection, 5) classification, and 6)
      interpretation and validation of candidate biomarkers. We review each step in the
      pipeline, presenting current and widely used bioinformatics methods. Furthermore,
      we analyze several publicly available cardiovascular genomics datasets to
      illustrate the pipeline. Finally, we summarize the current challenges and
      opportunities for further research.

PMID- 22614729
TI  - Alterations of deadenylase expression in acute leukemias: evidence for poly(a)
      specific ribonuclease as a potential biomarker.
AB  - BACKGROUND/AIMS: The degradation of mRNA is a key process in the control of gene
      expression correlated to anomalous cell proliferation. The rate-limiting step of
      mRNA degradation is the removal of the poly(A) tail by deadenylases. However,
      studies on deadenylase expression in cancer are limited. Herein, we analyzed the
      expression of several deadenylases from acute lymphoblastic leukemia (ALL) and
      acute myeloid leukemia (AML). METHODS: Clinical samples from patients diagnosed
      with ALL and AML were the source of leukemic cells. Extracts from leukemic and
      control cells were analyzed for deadenylase mRNA levels using qRT-PCR, and the
      protein levels of PARN and CNOT7 deadenylases using immunoblotting. RESULTS: RT
      PCR analysis revealed altered expression for CNOT6, CNOT6L, CNOT7 and PARN
      deadenylases. The most significant alterations were observed for PARN and CNOT7
      mRNA levels, which also reflect on the cognate protein level. Further analysis
      revealed that a significant amount of PARN is phosphorylated in ALL. CONCLUSIONS:
      We show that the expression of several deadenylases in acute leukemias is
      altered. The increase of PARN expression and the alteration of its
      phosphorylation status indicate important regulatory events. These data suggest
      that the role of deadenylases as auxiliary biomarkers and therapeutic targets
      should be meticulously investigated.

PMID- 22614730
TI  - Atrial waveform analysis using esophageal long-term electrocardiography reveals
      atrial ectopic activity.

PMID- 22614733
TI  - Dosimetric treatment course simulation based on a statistical model of deformable
      organ motion.
AB  - We present a method of modeling dosimetric consequences of organ deformation and
      correlated motion of adjacent organ structures in radiotherapy. Based on a few
      organ geometry samples and the respective deformation fields as determined by
      deformable registration, principal component analysis (PCA) is used to create a
      low-dimensional parametric statistical organ deformation model (Sohn et al 2005
      Phys. Med. Biol. 50 5893-908). PCA determines the most important geometric
      variability in terms of eigenmodes, which represent 3D vector fields of
      correlated organ deformations around the mean geometry. Weighted sums of a few
      dominating eigenmodes can be used to simulate synthetic geometries, which are
      statistically meaningful inter- and extrapolations of the input geometries, and
      predict their probability of occurrence. We present the use of PCA as a versatile
      treatment simulation tool, which allows comprehensive dosimetric assessment of
      the detrimental effects that deformable geometric uncertainties can have on a
      planned dose distribution. For this, a set of random synthetic geometries is
      generated by a PCA model for each simulated treatment course, and the dose of a
      given treatment plan is accumulated in the moving tissue elements via dose
      warping. This enables the calculation of average voxel doses, local dose
      variability, dose-volume histogram uncertainties, marginal as well as joint
      probability distributions of organ equivalent uniform doses and thus of TCP and
      NTCP, and other dosimetric and biologic endpoints. The method is applied to the
      example of deformable motion of prostate/bladder/rectum in prostate IMRT.
      Applications include dosimetric assessment of the adequacy of margin recipes,
      adaptation schemes, etc, as well as prospective 'virtual' evaluation of the
      possible benefits of new radiotherapy schemes.

PMID- 22614732
TI  - Lung metastasis from an ovarian granulosa cell tumor 36 years after the initial
      diagnosis: report of a case.
AB  - This report presents the case of a late relapse of an ovarian granulosa cell
      tumor (GCT) that metastasized to the lung 36 years after the initial diagnosis. A
      72-year-old female demonstrated multiple nodules with extrapleural signs on chest
      computed tomography. Positron emission tomography with (18)F-fluorodeoxyglucose
      ([(18)F]FDG-PET) showed that the nodules had no FDG avidity. The nodules, which
      appeared as polypoid lesions of the visceral pleura on thoracoscopy, were
      resected and diagnosed as pulmonary metastases from the GCT. This case report
      indicates that thorough thoracoscopic exploration of the pleural cavity is
      essential when intrathoracic nodules are seen on postoperative imaging
      examinations in GCT patients, even when the [(18)F]FDG-PET results are negative.

PMID- 22614731
TI  - Spontaneous rupture of the esophagus with extensive bowel necrosis caused by
      nonocclusive mesenteric ischemia: report of a case.
AB  - We report a case of spontaneous rupture of the esophagus accompanied by extensive
      bowel necrosis caused by nonocclusive mesenteric ischemia. The patient was
      treated successfully with prompt surgical intervention after an early diagnosis.
      A 61-year-old man was admitted to our hospital complaining of abdominal pain
      after drinking. On arrival, he was suffering shock. Thoracoabdominal computed
      tomography and esophagoscopy findings were highly suggestive of rupture of the
      esophagus above the esophagogastric junction and extensive bowel necrosis.
      Emergency laparotomy revealed extensive bowel necrosis from the jejunum to the
      transverse colon; thus, we resected the entire affected region and performed
      jejunostomy and transverse colostomy. After suturing the esophageal perforation
      directly, we performed intramediastinal packing of the omentum and inserted
      drains. The patient recovered well and was discharged from hospital on
      postoperative day 126. To the best of our knowledge, this is the first case
      report of spontaneous rupture of the esophagus with nonocclusive mesenteric
      ischemia.

PMID- 22614735
TI  - Cannabinoid-associated cell death mechanisms in tumor models (review).
AB  - In recent years, cannabinoids (the active components of Cannabis sativa) and
      their derivatives have received considerable interest due to findings that they
      can affect the viability and invasiveness of a variety of different cancer cells.
      Moreover, in addition to their inhibitory effects on tumor growth and migration,
      angiogenesis and metastasis, the ability of these compounds to induce different
      pathways of cell death has been highlighted. Here, we review the most recent
      results generating interest in the field of death mechanisms induced by
      cannabinoids in cancer cells. In particular, we analyze the pathways triggered by
      cannabinoids to induce apoptosis or autophagy and investigate the interplay
      between the two processes. Overall, the results reported here suggest that the
      exploration of molecular mechanisms induced by cannabinoids in cancer cells can
      contribute to the development of safe and effective treatments in cancer therapy.

PMID- 22614734
TI  - Lentiviral expression of anti-microRNAs targeting miR-27a inhibits proliferation
      and invasiveness of U87 glioma cells.
AB  - Glioma is a highly fatal malignant disease and its treatment options are limited.
      microRNAs represent a novel target for the treatment of cancer. In the present
      study, we used a lentiviral vector to stably express anti-microRNAs targeting the
      oncogenic miR-27a in U87 glioma cells. The stable expression of anti-miR-27a
      significantly reduced the proliferation and increased the accumulation of U87
      cells in the sub-G1 phase as determined by Cell Counting kit-8 (CCK-8) assays and
      flow cytometry, respectively. Results from the Matrigel transwell assay also
      indicated that the inhibition of miR-27a substantially impaired the invasiveness
      of U87 cells. By combining bioinformatic and proteomic approaches, we identified
      the mRNAs of 8 proteins upregulated in anti-miR-27a-expressing U87 cells as
      putative direct targets of miR-27a. Collectively, these data suggest that the
      lentiviral expression of anti-miR-27a is a feasible approach for the suppression
      of malignant phenotypes of glioma cells.

PMID- 22614736
TI  - Saccharin pre-exposure enhances appetitive flavor learning in pre-weanling rats.
AB  - In adult rats, data suggest that consumption of sweet tastes that do not deliver
      anticipated caloric consequences using high-intensity, non-caloric sweeteners,
      such as saccharin, interferes with learned relations that may contribute to
      energy balance. The goal of the present study was to assess the development of
      learning about sweet taste and calories by assessing whether pre-exposure to
      saccharin solutions reduces cue competition in pre-weanling rats. The results
      demonstrated that rats pre-exposed to saccharin and then trained with a novel
      grape flavor paired with a glucose-sweetened solution consumed more of the novel
      grape flavor presented alone than rats that had been pre-exposed to saccharin and
      given the grape flavor paired with water alone. No differences in intake of the
      novel grape flavor were observed in groups given pre-exposure to water or glucose
      solutions. Thus, by 15 days of age, rats appear to have established an
      association between sweet tastes and calories, and this association can be
      weakened by exposure to saccharin.

PMID- 22614737
TI  - Identification of possible cigarette smoke constituents responsible for muscle
      catabolism.
AB  - The age-related loss of muscle mass and strength also known as sarcopenia is
      significantly influenced by life style factors such as physical inactivity and
      impaired nutrition. Cigarette smoking is another life style habit that has been
      shown to be associated with sarcopenia and to affect skeletal muscle. Even today,
      smoking is still prevalent worldwide and is probably the most significant source
      of toxic chemicals exposure to humans. Cigarette smoke (CS) is a complex aerosol
      consisting of thousands of various constituents including reactive oxygen and
      nitrogen free radicals, toxic aldehydes and more. Previous epidemiological
      studies have identified tobacco smoking as a risk factor for sarcopenia.
      Clinical, in vivo and in vitro studies have revealed CS-induced skeletal muscle
      damage due to impaired muscle metabolism, increased inflammation and oxidative
      stress, over-expression of atrophy related genes and activation of various
      intracellular signaling pathways. This review aims to discuss and identify the
      components of CS that may promote catabolism of skeletal muscle.

PMID- 22614738
TI  - Kate Barany: a life of science, teaching, and service.
AB  - We celebrate the lives of Michael and Kate Barany in this issue of the Journal of
      Muscle Research and Cell Motility. Kate and Michael died within weeks of each
      other in 2011. Joe Chalovich has written about Michael and we write about Kate.
      As emphasized by Joe, Kate, and Michael were remarkable individuals who survived
      the Holocaust, the Hungarian revolution, and emerged from as much adversity as
      one might imagine to become productive scientists, educators, citizens, and
      symbols of the durability of the human spirit. They present their own story in an
      essay (Barany and Barany 2000) published in a monograph "Selected Topics in the
      History of Biochemistry." Rather than repeating much of the list of scientific
      achievements chronicled in these papers, we focus here on Kate, especially in her
      role as an individual and partner in science, while at the same time being an
      accomplished teacher, and a champion of women in science.

PMID- 22614739
TI  - Spatial-symbolic Query Engine in Anatomy.
AB  - OBJECTIVES: Currently, the primary means for answering anatomical questions such
      as 'what vital organs would potentially be impacted by a bullet wound to the
      abdomen?' is to look them up in textbooks or to browse online sources. In this
      work we describe a semantic web service and spatial query processor that permits
      a user to graphically pose such questions as joined queries over separately
      defined spatial and symbolic knowledge sources. METHODS: Spatial relations (e.g.
      anterior) were defined by two anatomy experts, and based on a 3-D volume of
      labeled images of the thorax, all the labeled anatomical structures were queried
      to retrieve the target structures for every query structure and every spatial
      relation. A web user interface and a web service were designed to relate existing
      symbolic information from the Foundational Model of Anatomy ontology (FMA) with
      spatial information provided by the spatial query processor, and to permit users
      to select anatomical structures and define queries. RESULTS: We evaluated the
      accuracy of results returned by the queries, and since there is no independent
      gold standard, we used two anatomy experts' opinions as the gold standard for
      comparison. We asked the same experts to define the gold standard and to define
      the spatial relations. The F-measure for the overall evaluation is 0.90 for rater
      1 and 0.56 for rater 2. The percentage of observed agreement is 99% and Cohen's
      kappa coefficient reaches 0.51. The main source of disagreement relates to issues
      with the labels used in the dataset, and not with the tool itself. CONCLUSIONS:
      In its current state the system can be used as an end-user application but it is
      likely to be of most use as a framework for building end-user applications such
      as displaying the results as a 3-D anatomical scene. The system promises
      potential practical utility for obtaining and navigating spatial and symbolic
      data.

PMID- 22614741
TI  - Assessment of post-stroke fatigue: the fatigue scale for motor and cognitive
      functions.
AB  - BACKGROUND/AIMS: Post-stroke fatigue (PSF) is an important but still
      controversial issue since knowledge on its nature is still humble. The aim of the
      present study was to characterize PSF beyond the subacute phase. METHODS: Thirty
      one stroke patients (gender: 6 female, 25 male; age range: 35-76 years; 28
      patients with ischemic stroke, 3 patients with hemorrhagic stroke; mean delay
      after stroke: 50.65 +/- 31.57 days) were recruited and assessed by measures of
      fatigue (Fatigue Scale for Motor and Cognitive Functions [FSMC], Fatigue Severity
      Scale, and Modified Fatigue Impact Scale), depression (Beck Depression Inventory
      Fast Screen), cognition (Brief Repeatable Battery of Neuropsychological Tests)
      and upper and lower extremity functions (Nine-Hole Peg Test and 25-foot walk).
      RESULTS: Depending on the different scales, PSF prevalence ranged from 16.1 to
      58.1%. Depression measures correlated significantly (r(29) >= 0.46; p < 0.01)
      with the results of all fatigue scales. Seventy-one percent of patients showed
      cognitive deficits in at least one cognitive domain. Cognitive fatigue measured
      by one subscale of the FSMC correlated most significantly with mental speed,
      working memory, and verbal short-term memory, while the motor subscale was
      associated with upper and lower extremity functions, mental speed, visual short
      term memory, and working memory. A differentiation between lesion localization
      and fatigue severity in the motor or cognitive domain was only possible when
      applying the FSMC. Patients with cortical lesions scored higher on the cognitive
      subscale, while patients with subcortical lesions showed higher physical subscale
      scores. CONCLUSION: The present pilot study revealed differences between lesion
      localization and subdomains of fatigue after stroke by applying a new fatigue
      scale (FSMC). The results underline the necessity for separate assessment of
      motor and cognitive fatigue in stroke patients.

PMID- 22614742
TI  - Macular vitreoretinal interface abnormalities in highly myopic eyes with
      posterior staphyloma: 5-year follow-up.
AB  - PURPOSE: To review prevalence, long-term progression, and prognosis of
      vitreoretinal interface modifications in pathologic myopia with posterior
      staphyloma and investigate foveal sensitivity and fixation stability. METHODS:
      Retrospective single-institution series of 214 eyes (116 patients) with
      pathologic myopia, axial length >30 mm, and posterior staphyloma. Exclusion
      criteria included follow-up less than five years, incomplete records, and/or less
      than three optical coherence tomography or microperimetry. Patients were divided
      into 5 groups according to optical coherence tomography: 1) epiretinal membrane
      without schisis (ERM); 2) macular retinal schisis (Schisis); 3) partial thickness
      macular hole (PTMH); 4) full-thickness macular hole (FTMH); and 5) posterior
      retinal detachment (PRD) with or without macular hole. Disease progression was
      defined as a visual acuity decrease of two or more lines associated to objective
      worsening of the optical coherence tomography and/or microperimetry. RESULTS:
      Vitreoretinal abnormalities at baseline were present in 116 of 204 patients
      (56.8%) and 214 of 408 eyes (52.4%); 98 of 116 patients (84.4%) showed bilateral
      involvement. Baseline visual acuity and foveal sensitivity varied significantly
      with ERM performing better and PRD worse than others; PTMH and FTMH did not
      differ. During the 66 months of average follow-up, 33 of 214 eyes (15.4%)
      required surgery and 13 of 33 eyes (39.3%) needed reintervention. Surgery rate
      significantly differed among groups: 2% for ERM, 20% to 25% for Schisis, PTMH,
      and FTMH, and up to 50% for PRD. Progression rate of Schisis and FTMH was the
      same, regardless of symptoms, while macula-off PRD always required surgery.
      Decrease of fixation stability and foveal sensitivity correlated to need for
      surgery, while baseline foveal sensitivity and fixation did not. CONCLUSION:
      Vitreoretinal interface pathology in pathologic myopia with posterior staphyloma
      encompasses a spectrum of conditions whose baseline functionality, prognosis,
      rate, and amount of progression vary significantly. Customized treatment for each
      different condition should be considered.

PMID- 22614743
TI  - The interferon signature and STAT1 expression in rheumatoid arthritis synovial
      fluid macrophages are induced by tumor necrosis factor alpha and counter
      regulated by the synovial fluid microenvironment.
AB  - OBJECTIVE: Type I interferons (IFNs) have emerged as potential activators of the
      IFN signature and elevated STAT-1 expression in rheumatoid arthritis (RA)
      synovium, but mechanisms that induce synovial IFN expression are unknown.
      Recently, tumor necrosis factor alpha (TNFalpha) was shown to induce a delayed
      IFN response in macrophages. We undertook this study to test whether TNFalpha,
      classically thought to activate inflammatory NF-kappaB target genes in RA, also
      contributes to the "IFN signature" in RA synovial macrophages. METHODS: Synovial
      fluid (SF) macrophages purified from 24 patients with RA and 18 patients with
      spondylarthritides (SpA) were lysed immediately after isolation or were cultured
      ex vivo in the absence or presence of blockade of endogenous type I IFN or
      TNFalpha. Expression of IFN-inducible target genes was measured by quantitative
      reverse transcription-polymerase chain reaction, and expression of their
      corresponding proteins was measured by enzyme-linked immunosorbent assay.
      RESULTS: Expression of an IFN signature and STAT1 in RA synovial macrophages was
      suppressed when type I IFNs or TNFalpha were blocked, whereas TNFalpha blockade
      did not affect expression of IFN response genes or STAT1 in SpA synovial
      macrophages. RA SF suppressed the IFN signature in RA synovial macrophages and in
      TNFalpha-, IFNalpha-, and IFNbeta-stimulated control macrophages. Type I IFNs
      suppressed expression of IL8 and MMP9 in RA synovial macrophages and in TNFalpha
      stimulated control macrophages. CONCLUSION: Our findings identify a new function
      of TNFalpha in RA synovitis by implicating TNFalpha as a major inducer of the RA
      synovial IFN response. The results suggest that the expression of IFN response
      genes in RA synovium is regulated by interplay between TNFalpha and opposing
      homeostatic factors expressed in the synovial microenvironment.

PMID- 22614744
TI  - Bipolar disorder is associated with HIV transmission risk behavior among patients
      in treatment for HIV.
AB  - This study examined HIV transmission risk behavior among 63 patients with bipolar
      disorder (BD), major depressive disorder, and no mood disorder; half had
      substance use disorders (SUDs). Patients with BD were more likely than others to
      report unprotected intercourse with HIV-negative partners and <95 % adherence to
      antiretroviral medications. In multivariate models, BD and SUD were independent
      predictors of both risk behaviors. Participants with poorer medication adherence
      were more likely to have detectable HIV viral loads and unprotected intercourse
      with HIV-negative partners. Patients with BD deserve careful evaluation and HIV
      prevention services to reduce HIV transmission risk behaviors.

PMID- 22614746
TI  - Predictors of relationship power among drug-involved women.
AB  - Gender-based relationship power is frequently linked to women's capacity to
      reduce sexual risk behaviors. This study offers an exploration of predictors of
      relationship power, as measured by the multidimensional and theoretically
      grounded sexual relationship power scale, among women in outpatient substance
      abuse treatment. Linear models were used to test nine predictors (age,
      race/ethnicity, education, time in treatment, economic dependence, substance use,
      sexual concurrency, partner abuse, and sex role orientation) of relationship
      power among 513 women participating in a multi-site HIV risk reduction
      intervention study. Significant predictors of relationship control included
      having a non-abusive male partner, only one male partner, and endorsing
      traditional masculine (or both masculine and feminine) sex role attributes.
      Predictors of decision-making dominance were interrelated, with substance use *
      partner abuse and age * sex role orientation interactions. Results contribute to
      the understanding of factors which may influence relationship power and to their
      potential role in HIV sexual risk reduction interventions.

PMID- 22614748
TI  - Electrochemistry at carbon nanotube forests: sidewalls and closed ends allow fast
      electron transfer.
AB  - The electrochemical properties of the closed ends and sidewalls of pristine
      carbon nanotube forests are investigated directly using a nanopipet
      electrochemical cell. Both are shown to promote fast electron transfer, without
      any activation or processing of the carbon nanotube material required, in
      contrast to the current model in the literature.

PMID- 22614745
TI  - Predictors of day-level sexual risk for young gay and bisexual men.
AB  - As HIV infection rates remain high among young gay and bisexual men,
      investigations into determinants of sexual risk are paramount. This study
      examined independent and interactive effects of substance use, mental health,
      perceived benefits of unprotected sex, and type of sex partner on odds of not
      using condoms. Analyses included 188 high-risk substance using HIV-negative and
      unknown status young gay and bisexual men (ages 18-29). Substance use and
      endorsing favorable attitudes towards unprotected sex strongly predicted sexual
      risk. Mental health moderated the relationship between partner type (main vs.
      casual) and condom use such that increased anxiety and depression were associated
      with increased odds of using condoms with main partners and not using condoms
      with casual partners. Understanding how these determinants of HIV risk converge
      to predict unprotected anal sex can identify essential risk relationships for
      prevention, obtain effects sizes of greater magnitude and prolonged
      sustainability, and build robust couples-based interventions.

PMID- 22614747
TI  - Moderno love: sexual role-based identities and HIV/STI prevention among men who
      have sex with men in Lima, Peru.
AB  - Role-based sexual identities structure male same-sex partnerships and influence
      HIV/STI epidemiology among MSM in Latin America. We explored shifting
      relationships between sexual roles, identities and practices among MSM in Lima,
      Peru, and implications for HIV/STI prevention. Patterns of HIV/STI epidemiology
      reflected differential risks for transmission within role-based partnerships with
      relatively low prevalences of HIV, syphilis, and HSV-2 but higher prevalences of
      urethral gonorrhea/chlamydia among activo MSM compared with moderno and pasivo
      participants. Qualitative analysis of how MSM in Peru integrate sexual
      identities, roles, and practices identified four key themes: pasivo role as a gay
      approximation of cultural femininity; activo role as a heterosexual consolidation
      of masculinity; moderno role as a masculine reconceptualization of gay identity;
      and role-based identities as social determinants of partnership, network, and
      community formation. The concept of role-based sexual identities provides a
      framework for HIV prevention for Latin American MSM that integrates sexual
      identities, practices, partnerships, and networks.

PMID- 22614749
TI  - NAFLD: The role of exercise in treating NAFLD.

PMID- 22614750
TI  - Cancer: Integrated epigenomic analysis sheds light on role of BMP4 in regulating
      cisplatin sensitivity in gastric cancer.

PMID- 22614751
TI  - Oesophagus: Predicting treatment efficacy in patients with achalasia.

PMID- 22614752
TI  - NAFLD: MRI versus biopsy to assess NAFLD.

PMID- 22614753
TI  - What is personalized medicine and what should it replace?
AB  - Personalized medicine is a new framework for medical care that involves modelling
      and simulation of a disease on the basis of its underlying mechanisms. This
      strategy must replace the 20(th) century paradigm of defining disease by
      pathology or associated signs and symptoms and conducting outcomes research that
      is based on the presence or absence of the disease syndrome. New technologies,
      including next-generation sequencing, the 'omics' and powerful computers provide
      massive amounts of accurate data. However, attempts to understand complex
      disorders by applying these new technologies within the 20(th) century framework
      have failed to produce the expected medical advances. To help physicians embrace
      a paradigm shift, the limitations of the old framework and major advantages of
      the new framework must be demonstrated. Chronic pancreatitis is an ideal complex
      disorder to study to consider the pros and cons of the two frameworks, because
      the pancreas is such a simple organ for disease modelling, and the advantages of
      personalized medicine are so profound.

PMID- 22614754
TI  - Recent advances in our understanding of hepatorenal syndrome.
AB  - Hepatorenal syndrome (HRS) is a serious complication of advanced cirrhosis with
      ascites. HRS develops as a result of abnormal haemodynamics, leading to
      splanchnic and systemic vasodilatation, but renal vasoconstriction. Increased
      bacterial translocation, various cytokines and mesenteric angiogenesis also
      contribute to splanchnic vasodilatation, and altered renal autoregulation is
      involved in the renal vasoconstriction. Type 1 HRS is usually initiated by a
      precipitating event associated with an exaggerated systemic inflammatory response
      that perturbs haemodynamics, resulting in multiorgan failure. An inadequate
      cardiac output with systolic incompetence increases the risk of renal failure.
      Vasoconstrictors are the main treatment in patients with type 1 HRS; terlipressin
      is the superior agent. Norepinephrine is similar to terlipressin in efficacy and
      can be used as an alternative. Transjugular intrahepatic portosystemic stent
      shunt might be applicable in a small number of patients with type 1 HRS and in
      most patients with type 2 HRS. Liver transplantation is the definitive treatment
      for HRS, and should be performed after reversal of HRS. In nonresponders to
      vasoconstrictor therapy, much controversy still exists as to whether to do
      simultaneous or sequential liver and kidney transplant. In general, patients who
      have had >8-12 weeks of pretransplant dialysis should be considered for combined
      liver-kidney transplantation.

PMID- 22614756
TI  - The transport of integral membrane proteins across the nuclear pore complex.
AB  - The nuclear envelope protects and organizes the genome. The nuclear pore
      complexes embedded in the nuclear envelope allow selective transport of
      macromolecules between the cytosol and nucleoplasm, and as such help to control
      the flow of information from DNA to RNA to proteins. A growing list of integral
      membrane proteins of the nuclear envelope are described to function in the
      organization of the genome, as well as the assembly of the NPCs. Here, we discuss
      how the nuclear pore complex may sort these proteins to obtain a specific protein
      composition of the inner membrane.

PMID- 22614755
TI  - The non-redundant function of cohesin acetyltransferase Esco2: some answers and
      new questions.
AB  - Cohesin and cohesin regulatory proteins function in an essential pathway enabling
      proper cohesion and segregation of sister chromatids. Additionally, these
      proteins are involved in double-strand break (DSB) repair and transcriptional
      regulation. Mutations in Establishment of cohesion 1 homolog 2 (Esco2), an
      evolutionary conserved cohesin acetyltransferase, are the cause of Roberts
      syndrome (RBS), a human congenital disorder. To explore the mechanism by which
      the deficiency in Esco2 affects cohesin's functions, we generated a mouse
      harboring a conditional Esco2 allele. To our surprise and in marked contrast to
      RBS, mouse Esco2 turns out to be a cell viability factor, the absence of which
      results in severe chromosome segregation defects and apoptosis. We found that the
      acetylation of the cohesin subunit Smc3 is significantly reduced in Esco2
      deficient cells resulting in a marked reduction of Sororin recruitment to
      several, but not all cohesin bound loci. Here, we provide evidence that Esco2 is
      also required for DSB repair, which is consistent with previous studies in RBS
      cells.

PMID- 22614757
TI  - Cell motility, morphology, viability and proliferation in response to
      nanotopography on silicon black.
AB  - Knowledge of cells' interactions with nanostructured materials is fundamental for
      bio-nanotechnology. We present results for how individual mouse fibroblasts from
      cell line NIH3T3 respond to highly spiked surfaces of silicon black that were
      fabricated by maskless reactive ion etching (RIE). We did standard measurements
      of cell viability, proliferation, and morphology on various surfaces. We also
      analyzed the motility of cells on the same surfaces, as recorded in time lapse
      movies of sparsely populated cell cultures. We find that motility and morphology
      vary strongly with nano-patterns, while viability and proliferation show little
      dependence on substrate type. We conclude that motility analysis can show a wide
      range of cell responses e.g. over a factor of two in cell speed to different nano
      topographies, where standard assays, such as viability or proliferation, in the
      tested cases show much less variation of the order 10-20%.

PMID- 22614758
TI  - Overexpression of the RD RNA binding protein in hepatitis C virus-related
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) often exhibits a poor prognosis due to metastatic
      spread caused by portal vein invasion (PVI). In the present study, we attempted
      to identify a novel therapeutic target related to PVI of HCC. Based on pooled
      genomic data, we identified RD RNA binding protein (RDBP), a member of the
      negative elongation factor (NELF) transcription elongation regulatory complex, to
      be preferentially overexpressed in HCC with PVI. We used quantitative reverse
      transcription polymerase chain reaction (RT-PCR) and immuno-histochemical
      analyses to investigate the relationship between RDBP mRNA and protein with
      metastatic potential in sample sets of hepatitis C virus (HCV)-related HCC and
      corresponding non-HCC liver tissues. We also used the small interfering RNA
      technique to examine the role of RDBP in invasion and proliferation of HCC cells
      in vitro. Our data showed that both mRNA and protein levels of RDBP were
      significantly higher in HCC compared to non-HCC liver tissue, and that these
      levels were also significantly higher in HCC with PVI compared to HCC without
      PVI. Multivariate analysis revealed that RDBP protein levels were an independent
      risk factor for early intrahepatic recurrence of HCC within 2 years of surgery.
      Knockdown of RDBP protein significantly inhibited the proliferation and invasion
      of cells in vitro. These data demonstrate that RDBP is related to the metastatic
      potential of HCC, suggesting a possible candidate for prevention of HCC cell
      metastasis.

PMID- 22614759
TI  - Dividing lines at the word boundary position helps reading in Chinese.
AB  - Unlike in English, the Chinese printing and writing systems usually do not
      respect a word boundary when they split lines; thus, characters belonging to a
      word can be on two different lines. In this study, we examined whether dividing a
      word across two lines interferes with Chinese reading and found that reading
      times were shorter when characters belonging to a word were on a single line
      rather than on adjacent lines. Eye movement data indicated that gaze durations in
      a region around the word boundary were longer and fixations were closer to the
      beginnings and ends of the lines when words were split across lines. These
      results suggest that words are processed as a whole in Chinese reading, so that
      word boundaries should be respected when deciding how to split lines in the
      Chinese writing system. They also suggest that the length of return sweeps in
      reading can be cognitively guided.

PMID- 22614760
TI  - Protective effect of myo-inositol hexaphosphate (phytate) on bone mass loss in
      postmenopausal women.
AB  - INTRODUCTION: The objective of this paper was to evaluate the relationship
      between urinary concentrations of InsP6, bone mass loss and risk fracture in
      postmenopausal women. MATERIALS AND METHODS: A total of 157 postmenopausal women
      were included in the study: 70 had low (<=0.76 MUM), 42 intermediate (0.76-1.42
      MUM) and 45 high (>=1.42 MUM) urinary phytate concentrations. Densitometry values
      for neck were measured at enrollment and after 12 months (lumbar spine and
      femoral neck), and 10-year risk fracture was calculated using the tool FRAX((r)).
      RESULTS: Individuals with low InsP6 levels had significantly greater bone mass
      loss in the lumbar spine (3.08 +/- 0.65 % vs. 0.43 +/- 0.55 %) than did those
      with high phytate levels. Moreover, a significantly greater percentage of women
      with low than with high InsP6 levels showed more than 2 % of bone mass loss in
      the lumbar spine (55.6 vs. 20.7 %). The 10-year fracture probability was also
      significantly higher in the low-phytate group compared to the high-phytate group,
      both in hip (0.37 +/- 0.06 % vs 0.18 +/- 0.04 %) and major osteoporotic fracture
      (2.45 +/- 0.24 % vs 1.83 +/- 0.11 %). DISCUSSION: It can be concluded that high
      urinary phytate concentrations are correlated with reduced bone mass loss in
      lumbar spine over 12 months and with reduced 10-year probability of hip and major
      osteoporotic fracture, indicating that increased phytate consumption can prevent
      development of osteoporosis.

PMID- 22614761
TI  - Follicular lymphoma presenting with marked splenomegaly: report of three cases.
AB  - Marked splenomegaly as the main presenting sign in follicular lymphoma (FL) is
      rare. The clinical and morphologic findings of 3 FL patients with massive
      splenomegaly and slight or no lymphadenopathy are presented. All cases had
      massive splenomegaly, and 2 had minimal peripheral lymphadenopathy with bone
      marrow infiltration, which is the major involved site besides the spleen.
      Histologically, various sizes of micronodules, composed of medium-sized
      centrocytes, were present in the white pulp in 2 cases in whom splenectomy was
      performed. The other case was complicated by nephrotic syndrome and showed
      aggregates of packed small lymphocytes in the spleen and renal parenchyma. Tumor
      cells were positive for CD10, CD20, bcl-2, and bcl-6. Since these cases are
      clinically similar to splenic marginal zone lymphoma, recognition of this disease
      and selection of the appropriate therapy are needed.

PMID- 22614763
TI  - A Skew-t space-varying regression model for the spectral analysis of resting
      state brain activity.
AB  - It is known that in many neurological disorders such as Down syndrome, main brain
      rhythms shift their frequencies slightly, and characterizing the spatial
      distribution of these shifts is of interest. This article reports on the
      development of a Skew-t mixed model for the spatial analysis of resting state
      brain activity in healthy controls and individuals with Down syndrome. Time
      series of oscillatory brain activity are recorded using magnetoencephalography,
      and spectral summaries are examined at multiple sensor locations across the
      scalp. We focus on the mean frequency of the power spectral density, and use
      space-varying regression to examine associations with age, gender and Down
      syndrome across several scalp regions. Spatial smoothing priors are incorporated
      based on a multivariate Markov random field, and the markedly non-Gaussian nature
      of the spectral response variable is accommodated by the use of a Skew-t
      distribution. A range of models representing different assumptions on the
      association structure and response distribution are examined, and we conduct
      model selection using the deviance information criterion. (1) Our analysis
      suggests region-specific differences between healthy controls and individuals
      with Down syndrome, particularly in the left and right temporal regions, and
      produces smoothed maps indicating the scalp topography of the estimated
      differences. 

PMID- 22614764
TI  - Plasma viscosity in patients with metabolic syndrome.
AB  - BACKGROUND AND AIM: Plasma viscosity, which is affected by plasma lipid and
      protein composition, is a hemorheological parameter accepted as an early
      cardiovascular risk factor. In this study we aimed to investigate the alterations
      in plasma viscosity in patients with metabolic syndrome since both are early
      predictors of CVD. MATERIAL AND METHODS: A total number of 70 patients aged
      between 25-55 years with the diagnosis of metabolic syndrome according to IDF
      2005 criteria and 32 age and sex matched healthy subjects were allocated
      consecutively in the study. Body mass index (BMI), arterial blood pressure, blood
      glucose, total cholesterol, HDL and triglyceride levels were measured and plasma
      viscosity was measured. The results of patients with MS and healthy subjects were
      compared. Correlation between components of the Metabolic Syndrome and plasma
      viscosity was assessed. RESULTS: BMI, systolic and diastolic blood pressure,
      waist circumference, serum lipid and glucose levels and plasma viscosity levels
      were higher in patient group (p < 0.001). A positive correlation was determined
      between plasma viscosity and waist circumference, hypertension and serum lipid
      levels (r = 0.401, p = 0.003). CONCLUSION: Plasma viscosity is increased in
      patients with metabolic syndrome and it is associated with waist circumference,
      hypertension and plasma lipid levels.

PMID- 22614766
TI  - Wnt3a upregulates prostaglandin F2alpha-stimulated vascular endothelial growth
      factor synthesis in osteoblasts.
AB  - It is known that Wnt3a affects bone metabolism via the canonical Wnt/beta-catenin
      signaling pathway. We have previously shown that prostaglandin F2alpha
      (PGF2alpha) stimulates the synthesis of vascular endothelial growth factor (VEGF)
      and interleukin-6 (IL-6) via mitogen-activated protein (MAP) kinases, including
      p44/p42 MAP kinase, p38 MAP kinase and stress-activated protein kinase (SAPK)/c
      Jun N-terminal kinase (JNK) in osteoblast-like MC3T3-E1 cells. In the present
      study, we investigated the effects of Wnt3a on the synthesis of VEGF or IL-6
      stimulated by PGF2alpha in MC3T3-E1 cells using an ELISA kit and various
      antibodies. Cells were cultured and pretreated with various doses of Wnt3a or
      SB216763, an inhibitor of glycogen synthase kinase 3beta, prior to western
      blotting. Wnt3a significantly enhanced the PGF2alpha-stimulated VEGF release but
      had little effect on the PGF2alpha-stimulated IL-6 release. SB216763 markedly
      amplified the PGF2alpha-stimulated VEGF release without affecting the IL-6
      release, similar to Wnt3a. Wnt3a failed to affect the PGF2alpha-induced
      phosphorylation of p44/p42 MAP kinase, p38 MAP kinase or SAPK/JNK. These results
      strongly suggest that Wnt3a upregulates VEGF synthesis stimulated by PGF2alpha
      via activation of the canonical pathway in osteoblasts without affecting IL-6
      synthesis.

PMID- 22614767
TI  - Hypertonic saline and acute wheezing in preschool children.
AB  - BACKGROUND: Most acute wheezing episodes in preschool children are associated
      with rhinovirus. Rhinovirus decreases extracellular adenosine triphosphate
      levels, leading to airway surface liquid dehydration. This, along with submucosal
      edema, mucus plaques, and inflammation, causes failure of mucus clearance. These
      preschool children do not respond well to available treatments, even oral
      steroids. This calls for pro-mucus clearance and prohydration treatments such as
      hypertonic saline in wheezing preschool children. METHODS: Randomized,
      controlled, double-blind study. Forty-one children (mean age 31.9 +/- 17.4
      months, range 1-6 years) presented with wheezing to the emergency department were
      randomized after 1 albuterol inhalation to receive either 4 mL of hypertonic
      saline 5% (HS) (n = 16) or 4 mL of normal saline (NS) (n = 25), both with 0.5 mL
      albuterol, twice every 20 minutes in the emergency department and 4 times a day
      thereafter if hospitalized. The primary outcome measured was length of stay (LOS)
      and the secondary outcomes were admission rate (AR) and clinical severity score.
      RESULTS: The LOS was significantly shorter in the HS than in the NS group: median
      2 days (range 0-6) versus 3 days (range 0-5) days (P = .027). The AR was
      significantly lower in the HS than the NS group: 62.2% versus 92%. Clinical
      severity score improved significantly in both groups but did not reach
      significance between them. CONCLUSIONS: Using HS inhalations significantly
      shortens LOS and lowers AR in preschool children presenting with an acute
      wheezing episode to the emergency department.

PMID- 22614768
TI  - Cardiovascular risk factors in children and young adults born to preeclamptic
      pregnancies: a systematic review.
AB  - BACKGROUND AND OBJECTIVE: Preeclampsia is an independent cardiovascular risk
      factor for the mother, and recent studies reveal that offspring of affected
      pregnancies also may have an increased cardiovascular risk. Our objective was to
      examine evidence for increased cardiovascular risk factors in children exposed to
      preeclampsia in utero. METHODS: We performed a systematic review and meta
      analysis on studies reporting traditional cardiovascular risk factors in those
      exposed to preeclampsia compared to controls. Information was extracted on the
      classic cardiovascular risk factors, including blood pressure, lipid profile,
      glucose metabolism, and BMI from articles published between 1948 and August 2011
      in Medline and Embase. RESULTS: Eighteen studies provided cumulated data on
      45,249 individuals. In utero exposure to preeclampsia was associated with a 2.39
      mm Hg (95% confidence interval: 1.74-3.05; P < .0001) higher systolic and a 1.35
      mm Hg (95% confidence interval: 0.90-1.80; P < .00001) higher diastolic blood
      pressure during childhood and young adulthood. BMI was increased by 0.62 kg/m2 (P
      < .00001). Associations were similar in children and adolescents, for different
      genders, and with variation in birth weight. There was insufficient evidence to
      identify consistent variation in lipid profile or glucose metabolism.
      CONCLUSIONS: Young offspring of pregnancies complicated by preeclampsia already
      have increased blood pressure and BMI, a finding that may need to be considered
      in future primary prevention strategies for cardiovascular disease.

PMID- 22614769
TI  - Childhood cancer incidence trends in association with US folic acid fortification
      (1986-2008).
AB  - OBJECTIVE: Epidemiologic evidence indicates that prenatal vitamin supplementation
      reduces risk for some childhood cancers; however, a systematic evaluation of
      population-based childhood cancer incidence trends after fortification of
      enriched grain products with folic acid in the United States in 1996-1998 has not
      been previously reported. Here we describe temporal trends in childhood cancer
      incidence in association with US folic acid fortification. METHODS: Using
      Surveillance, Epidemiology, and End Results program data (1986-2008), we
      calculated incidence rate ratios and 95% confidence intervals to compare pre- and
      postfortification cancer incidence rates in children aged 0 to 4 years. Incidence
      trends were also evaluated by using joinpoint and loess regression models.
      RESULTS: From 1986 through 2008, 8829 children aged 0 to 4 years were diagnosed
      with malignancies, including 3790 and 3299 in utero during the pre- and
      postfortification periods, respectively. Pre- and postfortification incidence
      rates were similar for all cancers combined and for most specific cancer types.
      Rates of Wilms tumor (WT), primitive neuroectodermal tumors (PNETs), and
      ependymomas were significantly lower postfortification. Joinpoint regression
      models detected increasing WT incidence from 1986 through 1997 followed by a
      sizable decline from 1997 through 2008, and increasing PNET incidence from 1986
      through 1993 followed by a sharp decrease from 1993 through 2008. Loess curves
      indicated similar patterns. CONCLUSIONS: These results provide support for a
      decrease in WT and possibly PNET incidence, but not other childhood cancers,
      after US folic acid fortification.

PMID- 22614770
TI  - Neurocognitive phenotype of isolated methylmalonic acidemia.
AB  - OBJECTIVE: Methylmalonic acidemia (MMA) is a metabolic disorder with a poorly
      defined long-term neurocognitive phenotype. We studied the neuropsychological
      outcomes of patients and examined clinical covariates that influenced cognition.
      METHODS: A diverse cohort with mut, cblA, or cblB subtypes of isolated MMA (N =
      43), ages 2 to 32 years, were evaluated at a single center over a 6-year period.
      The influence of clinical, laboratory, and metabolic parameters on
      neuropsychological testing results was determined. RESULTS: Early-onset mut
      patients (n = 21) manifested the most severe neurocognitive impairments, with a
      mean +/- SD full-scale IQ (FSIQ) of 71.1 +/- 14.75. Late-onset mut patients (n =
      6) had a mean FSIQ of 88.5 +/- 27.62. cblA (n = 7), cblB (n = 6), and mut
      patients diagnosed prenatally or by newborn screening (n = 3) obtained mean FSIQs
      in the average range (100.7 +/- 10.95, 96.6 +/- 10.92, and 106.7 +/- 6.66,
      respectively). Hyperammonemia at diagnosis and the presence of a seizure disorder
      were associated with a lower FSIQ (P = .001 and P = .041, respectively), but
      other clinical variables, including basal ganglia injury and mutation status, did
      not. FSIQ remained stable over longitudinal testing (n = 10). Decreased scores on
      processing speed, compared with all other intellectual domains, emerged as a
      specific neurocognitive manifestation. CONCLUSIONS: The neurocognitive outcomes
      seen in isolated MMA are highly variable. An earlier age of disease onset, the
      presence of hyperammonemia at diagnosis, and a history of seizures were
      associated with more severe impairment. In all patient subtypes, selective
      deficits in processing speed were present.

PMID- 22614771
TI  - Transient neonatal hypocalcemia: presentation and outcomes.
AB  - OBJECTIVE: To determine the incidence of moderate-to-severe transient neonatal
      hypocalcemia in term neonates and to describe the characteristics of affected
      infants and the outcomes of their management. METHODS: We reviewed medical
      records of all term infants <31 days of age who presented to Children's Medical
      Center Dallas from 2001 to 2009 with hypocalcemia (ionized calcium <1.00 mmol/L
      [4.00 mg/dL]). RESULTS: Seventy-eight infants met criteria. Median (interquartile
      range) age at admission was 8.0 (7.0-10.0) days, and median duration of admission
      was 3.0 (2.0-4.0) days. Most infants were male (71.8%) and Hispanic (62.8%).
      Neonates were generally severely hypocalcemic and hyperphosphatemic. Seventy-five
      of 78 were hypomagnesemic, and the majority had low or inappropriately normal
      parathyroid hormone responses. Levels of 25-hydroxyvitamin D were <= 62.4 nmol/L
      (25 ng/mL) in all 42 infants in whom they were determined. All infants responded
      to therapy of limited duration with 1 or more of the following: calcium
      supplements, calcitriol, low phosphorus formula, and magnesium supplementation.
      Neuroimaging did not affect management decisions in any neonate. CONCLUSIONS:
      Moderate-to-severe late-onset neonatal hypocalcemia is more common in Hispanic
      and male infants, is often a sign of coexistent vitamin D insufficiency or
      deficiency and hypomagnesemia, and is readily managed with therapy of limited
      duration. Neonates presenting with seizures who are found to be hypocalcemic are
      unlikely to benefit from neuroimaging evaluations.

PMID- 22614772
TI  - Missed opportunities in the referral of high-risk infants to early intervention.
AB  - OBJECTIVE: Using a statewide population-based data source, we describe current
      neonatal follow-up referral practices for high-risk infants with developmental
      delays throughout California. METHODS: From a cohort analysis of quality
      improvement data from 66 neonatal follow-up programs in the California Children's
      Services and California Perinatal Quality Care Collaborative High-Risk Infant
      Follow-Up Quality of Care Initiative, 5129 high-risk infants were evaluated at
      the first visit between 4 and 8 months of age in neonatal follow-up. A total of
      1737 high-risk infants were evaluated at the second visit between 12 and 16
      months of age. We calculated referral rates in relation to developmental status
      (high versus low concern) based on standardized developmental testing or
      screening. RESULTS: Among infants with low concerns (standard score >70 or passed
      screen) at the first visit, 6% were referred to early intervention; among infants
      with high concerns, 28% of infants were referred to early intervention. Even
      after including referrals to other (private) therapies, 34% infants with high
      concerns did not receive any referrals. These rates were similar for the second
      visit. CONCLUSIONS: In spite of the specialization of neonatal follow-up programs
      to identify high-risk infants with developmental delays, a large proportion of
      potentially eligible infants were not referred to early intervention.

PMID- 22614773
TI  - Risky music-listening behaviors and associated health-risk behaviors.
AB  - OBJECTIVE: To examine, among adolescents and emerging adults attending inner-city
      lower education, associations between risky music-listening behaviors (from MP3
      players and in discotheques and at pop concerts) and more traditional health-risk
      behaviors: substance use (cigarettes, alcohol, cannabis, and hard drugs) and
      unsafe sexual intercourse. METHODS: A total of 944 students in Dutch inner-city
      senior-secondary vocational schools completed questionnaires about their music
      listening and traditional health-risk behaviors. Multiple logistic regression
      analyses were used to examine associations between music-listening and
      traditional health-risk behaviors. RESULTS: Risky MP3-player listeners used
      cannabis more often during the past 4 weeks. Students exposed to risky sound
      levels during discotheque and pop concert attendance used cannabis less often
      during the past 4 weeks, were more often binge drinkers, and reported
      inconsistent condom use during sexual intercourse. CONCLUSIONS: The coexistence
      of risky music-listening behaviors with other health-risk behaviors provides
      evidence in support of the integration of risky music-listening behaviors within
      research on and programs aimed at reducing more traditional health-risk
      behaviors, such as substance abuse and unsafe sexual intercourse.

PMID- 22614774
TI  - Effect of a single inhalation of laninamivir octanoate in children with
      influenza.
AB  - OBJECTIVE: The purpose of this study was to compare the efficiency and safety of
      a new neuraminidase inhibitor, laninamivir octanoate (LO), with zanamivir (ZN) in
      pediatric patients with influenza. METHODS: One hundred twelve pediatric patients
      <= 15 years, diagnosed with a rapid diagnostic test as having influenza from
      January to May 2011, were randomly assigned to the LO group or the ZN group, and
      their parents were asked to complete a questionnaire during the recovery at home.
      The LO group was instructed to inhale LO once (20 or 40 mg depending on age), and
      the ZN group was instructed to inhale ZN (20 mg) twice daily for 5 days. RESULTS:
      The LO group (n = 55) and the ZN group (n = 57) were well balanced. Finally, 44
      patients in the LO group and 41 patients in the ZN group could be evaluated.
      Median times to fever resolution after initial treatment were 36 hours in the LO
      group and 37 hours in the ZN group. No differences were observed between the 2
      groups with respect to the frequencies of asthmatic symptoms, pneumonia,
      gastrointestinal symptoms, or abnormal behaviors. Six younger children could not
      inhale LO well for technical reasons. CONCLUSIONS: Our data suggest that the
      efficiency and safety of LO are the same as those of ZN in pediatric patients
      with influenza but that LO may be more convenient than ZN because it requires
      only a single inhalation. However, younger patients may not inhale LO
      efficiently.

PMID- 22614775
TI  - Mortality and neonatal morbidity among infants 501 to 1500 grams from 2000 to
      2009.
AB  - OBJECTIVE: To identify changes in mortality and neonatal morbidities for infants
      with birth weight 501 to 1500 g born from 2000 to 2009. METHODS: There were
      355806 infants weighing 501 to 1500 g who were born in 2000-2009. Mortality
      during initial hospitalization and major neonatal morbidity in survivors (early
      and late infection, chronic lung disease, necrotizing enterocolitis, severe
      retinopathy of prematurity, severe intraventricular hemorrhage, and
      periventricular leukomalacia) were assessed by using data from 669 North American
      hospitals in the Vermont Oxford Network. RESULTS: From 2000 to 2009, mortality
      for infants weighing 501 to 1500 g decreased from 14.3% to 12.4% (difference, 
      1.9%; 95% confidence interval, -2.3% to -1.5%). Major morbidity in survivors
      decreased from 46.4% to 41.4% (difference, -4.9%; 95% confidence interval, -5.6%
      to -4.2%). In 2009, mortality ranged from 36.6% for infants 501 to 750 g to 3.5%
      for infants 1251 to 1500 g, whereas major morbidity in survivors ranged from
      82.7% to 18.7%. In 2009, 49.2% of all very low birth weight infants and 89.2% of
      infants 501 to 750 g either died or survived with a major neonatal morbidity.
      CONCLUSIONS: Mortality and major neonatal morbidity in survivors decreased for
      infants with birth weight 501 to 1500 g between 2000 and 2009. However, at the
      end of the decade, a high proportion of these infants still either died or
      survived after experiencing >= 1 major neonatal morbidity known to be associated
      with both short- and long-term adverse consequences.

PMID- 22614776
TI  - Brief motivational interviewing intervention for peer violence and alcohol use in
      teens: one-year follow-up.
AB  - BACKGROUND AND OBJECTIVES: Emergency department (ED) visits present an
      opportunity to deliver brief interventions (BIs) to reduce violence and alcohol
      misuse among urban adolescents at risk for future injury. Previous analyses
      demonstrated that a BI resulted in reductions in violence and alcohol
      consequences up to 6 months. This article describes findings examining the
      efficacy of BIs on peer violence and alcohol misuse at 12 months. METHODS:
      Patients (14-18 years of age) at an ED reporting past year alcohol use and
      aggression were enrolled in the randomized control trial, which included
      computerized assessment, random assignment to control group or BI delivered by a
      computer or therapist assisted by a computer. The main outcome measures (at
      baseline and 12 months) included violence (peer aggression, peer victimization,
      violence-related consequences) and alcohol (alcohol misuse, binge drinking,
      alcohol-related consequences). RESULTS: A total of 3338 adolescents were screened
      (88% participation). Of those, 726 screened positive for violence and alcohol use
      and were randomly selected; 84% completed 12-month follow-up. In comparison with
      the control group, the therapist assisted by a computer group showed significant
      reductions in peer aggression (P < .01) and peer victimization (P < .05) at 12
      months. BI and control groups did not differ on alcohol-related variables at 12
      months. CONCLUSIONS: Evaluation of the SafERteens intervention 1 year after an ED
      visit provides support for the efficacy of computer-assisted therapist brief
      intervention for reducing peer violence.

PMID- 22614777
TI  - Prevalence of retinal hemorrhages in critically ill children.
AB  - BACKGROUND: Retinal hemorrhages (RHs) with encephalopathy and subdural bleeding
      are considered suggestive of abusive head trauma (AHT). Existing studies
      describing RH focus on AHT and have potential selection bias. We undertook a
      prospective observational study to define the prevalence, distribution, and
      extent of RH in critically ill children. METHODS: From February 2008 to December
      2009, emergency intensive care admissions >= 6 weeks of age underwent dilated
      retinal examination by either a pediatric ophthalmologist or RetCam (retinal
      photograph) imaging after written informed consent. Patients with suspected or
      proven AHT, penetrating eye trauma, and elective admissions were excluded.
      RESULTS: The prevalence of RH was 15.1% (24/159; 95% confidence interval [CI]:
      9.5%-21%); 16/24 (66%) mild, and 2/24 (8%) moderate. Severe multilayered RH were
      seen in only 6 patients (3.7%), 3 with myeloid leukemia and sepsis, 2 with severe
      accidental head injury, and 1 with severe coagulopathy secondary to late onset
      hemorrhagic disease of newborn. There was no detectable impact of age, gender,
      seizures, coagulopathy or cardiopulmonary resuscitation on prevalence of severe
      multilayered RH; however, sepsis (odds ratio: 3.2; 95% CI: 1.3-8.0, P = .018) and
      coagulopathy (odds ratio: 2.8; 95% CI: 1.2-7.0, P = .025) were significantly
      associated with any RH. Only admission diagnosis was independently associated
      with severe multilayered RH on logistic regression. CONCLUSIONS: RHs were seen in
      critically ill children with a prevalence of 15.1% (24/159); however, most were
      mild. Severe multilayered RH resembling those described in AHT were rare (6/24)
      and were only seen in patients with fatal accidental trauma, severe coagulopathy,
      sepsis with myeloid leukemia, or a combination of these factors.

PMID- 22614778
TI  - Prevalence of cardiovascular disease risk factors among US adolescents, 1999
      2008.
AB  - OBJECTIVE: Overweight and obesity during adolescence are associated with an
      increased risk for cardiovascular disease (CVD) risk factors. The objective of
      this study was to examine the recent trends in the prevalence of selected
      biological CVD risk factors and the prevalence of these risk factors by
      overweight/obesity status among US adolescents. METHODS: The NHANES is a cross
      sectional, stratified, multistage probability sample survey of the US civilian,
      noninstitutionalized population. The study sample included 3383 participants aged
      12 to 19 years from the 1999 through 2008 NHANES. RESULTS: Among the US
      adolescents aged 12 to 19 years, the overall prevalence was 14% for
      prehypertension/hypertension, 22% for borderline-high/high low-density
      lipoprotein cholesterol, 6% for low high-density lipoprotein cholesterol (<35
      mg/dL), and 15% for prediabetes/diabetes during the survey period from 1999 to
      2008. No significant change in the prevalence of prehypertension/hypertension
      (17% and 13%) and borderline-high/high low-density lipoprotein cholesterol (23%
      and 19%) was observed from 1999-2000 to 2007-2008, but the prevalence of
      prediabetes/diabetes increased from 9% to 23%. A consistent dose-response
      increase in the prevalence of each of these CVD risk factors was observed by
      weight categories: the estimated 37%, 49%, and 61% of the overweight, obese, and
      normal-weight adolescents, respectively, had at least 1 of these CVD risk factors
      during the 1999 through 2008 study period. CONCLUSIONS: The results of this
      national study indicate that US adolescents carry a substantial burden of CVD
      risk factors, especially those youth who are overweight or obese.

PMID- 22614779
TI  - A new era in neonatology brain care: we can do better.

PMID- 22614780
TI  - Predictors of survival in children born with Down syndrome: a registry-based
      study.
AB  - OBJECTIVE: To examine the influence of fetal and maternal characteristics on the
      survival of children born with Down syndrome. METHODS: We used prospectively
      collected population-based data on Down syndrome extracted from the UK Northern
      Congenital Abnormality Survey (NorCAS), January 1, 1985-December 31, 2003,
      matched to hospital and national mortality records to January 29, 2008, to
      determine survival status of liveborn children. Survival to 20 years was
      estimated by using Kaplan-Meier methods. Cox proportional hazards regression was
      used to examine factors that predict survival. RESULTS: A total of 1115 Down
      syndrome pregnancies were notified to NorCAS during the 19 years, a total
      prevalence of 16.8 (95% CI, 15.8-17.8) per 10,000 live births and stillbirths. Of
      these, 5.4% resulted in a spontaneous fetal loss (late miscarriage >= 20 weeks
      and stillbirth), 31.7% in a termination of pregnancy, and 63.0% in a live birth.
      Survival status was known for 95.3% of live births; 16.6% resulted in a death.
      Year of birth (P < .001), gestational age at delivery (P < .001), standardized
      birth weight (P < .001), karyotype (P < .01), and presence of additional
      structural anomalies (P < .001) were significant predictors of survival. Infant
      gender, plurality, maternal age, and maternal deprivation were not significant
      predictors of survival. CONCLUSIONS: These robust estimates of predictors of
      survival are important for the prenatal counseling of parents whose pregnancy is
      affected by Down syndrome and for health care planning for the future care needs
      of these children.

PMID- 22614781
TI  - Association of stem cell marker expression pattern and survival in human biliary
      tract cancer.
AB  - The aim of this study was to investigate the molecular and protein expression
      pattern of markers of stemness phenotype and its clinicopathological significance
      in human biliary tract cancer (BTC). Human BTC cell lines (CCLP-1, Egi-1, MzChA
      1, MzChA-2, SkChA-1, TFK-1 and GBC) were analyzed in vitro and in
      xenotransplanted animals for expression of markers of stemness and compared to
      tissue microarrays (TMA) of 34 cases of human BTC with complete
      pathomorphological and clinical data (survival). Molecular analyses on the mRNA
      and protein level included makers of stemness and progenitor (Bmi-1, Sox-2,
      Nestin, CD133, CD44 and Nanog), proliferation and differentiation (cell cycle
      proteins, intermediate filaments). The investigated BTC samples showed a low to
      moderate and partially significantly different expression pattern of the stem
      cell markers in vitro, in vivo and in TMA. Hierarchical cluster analysis
      identified subgroups with homogenous expression of stem cell markers
      significantly differing with respect to cytokeratin expression in xenografts and
      Ki67 proliferation marker in human TMA, respectively - thus indicating possible
      heterogeneous carcinogenesis pathways in BTC. Additionally, these stem cell
      markers could be linked to morphology and molecular markers of proliferation and
      differentiation on the mRNA and protein level. Finally, survival analysis
      identified the combination of CD133 and CD44 as an independent prognostic factor
      yet their value as prognostic factors need testing in prospective study design.

PMID- 22614782
TI  - [Tumor resistance to HER2 inhibitors: the drug sedimentation concept].
AB  - Twenty years have passed between the discovery of oncogene HER2, the description
      of its implication in mammary carcinogenesis, and the development of specific
      targeted therapies. To date, trastuzumab and lapatinib are the two anti-HER2
      targeted therapies commonly used, demonstrating therapeutic effects. Although
      their clinical efficacy seems to be exclusively related to the amplification of
      the HER2 gene or to the overexpression of the protein, these factors are not
      sufficient since tumors can develop resistance. Because of a better knowledge in
      those mechanisms of resistance, novel therapeutic agents could help to bypass
      them. How should these be used with respect to current anti-HER2 targeted
      therapies? Recent notions such as oncogene addiction, tumor cell dormancy and
      residual disease led us to propose a new entity that we named the "sedimentation
      strategy", in which distinct targeted approaches are summed during the treatment
      of metastatic breast cancer patients.

PMID- 22614783
TI  - The role of maternal stress during pregnancy, maternal discipline, and child COMT
      Val158Met genotype in the development of compliance.
AB  - Maternal discipline is an important predictor of child committed compliance.
      Maternal stress can affect both parenting and child development. In a large
      population-based cohort study (N = 613) we examined whether maternal discipline
      mediated the association between maternal stress during pregnancy and child
      compliance, and whether COMT or DRD4 polymorphisms moderated the association
      between maternal discipline and child compliance. Family-related and general
      stress were measured through maternal self-report and genetic material was
      collected through cord blood sampling at birth. Mother-child dyads were observed
      at 36 months in disciplinary tasks in which the child was not allowed to touch
      attractive toys. Maternal discipline and child compliance were observed in two
      different tasks and independently coded. The association between family stress
      during pregnancy and child committed compliance was mediated by maternal positive
      discipline. Children with more COMT Met alleles seemed more susceptible to
      maternal positive discipline than children with more COMT Val alleles.

PMID- 22614784
TI  - Cryptotanshinone induces cell cycle arrest and apoptosis of multidrug resistant
      human chronic myeloid leukemia cells by inhibiting the activity of eukaryotic
      initiation factor 4E.
AB  - Cryptotanshinone (CPT), a diterpene quinone isolated from Salvia miltiorrhiza, is
      recently reported to have obvious anticancer activities against diverse cancer
      cells. However, the effect and regulatory mechanism of CPT remain unclear in
      human chronic myeloid leukemia (CML) cells. In this study, we investigated the
      antiproliferative activity of CPT on the multidrug resistant CML cells K562/ADM.
      Our results demonstrated that CPT decreased the cell viability of K562/ADM cells
      by inducing cell cycle arrest and apoptosis through suppressing the expression of
      cyclin D1 and Bcl-2. Further studies indicated that CPT mainly functions at post
      transcriptional levels, suggesting the involvement of eukaryotic initiation
      factor 4E (eIF4E). CPT significantly reduced the expression and activity of eIF4E
      in K562/ADM cells. Overexpression of eIF4E obvious conferred resistance to the
      CPT antiproliferation and proapoptotic activity as well as the cyclin D1 and Bcl
      2 expressions. Knockdown of eIF4E significantly reduced the inhibitory effect of
      CPT in K562/ADM, confirming the participation of eIF4E during CPT function
      process. More importantly, the relative inhibitory efficiency of CPT positively
      correlated with the reductions on eIF4E in primary CML specimens. These results
      demonstrated that CPT played antitumor roles in K562/ADM cells by inhibiting the
      eIF4E regulatory system. Our results provide a novel anticancer mechanism of CPT
      in human CML cells.

PMID- 22614785
TI  - An improved method for nematode infection assays in Drosophila larvae.
AB  - The infective juveniles (IJs) of entomopathogenic nematodes (EPNs) seek out host
      insects and release their symbiotic bacteria into their body cavity causing
      septicaemia, which eventually leads to host death. The interaction between EPNs
      and their hosts are only partially understood, in particular the host immune
      responses appears to involve pathways other than phagocytosis and the canonical
      transcriptional induction pathways. These pathways are genetically tractable and
      include for example clotting factors and lipid mediators. The aim of this study
      was to optimize the nematode infections in Drosophila melanogaster larvae, a well
      studied and genetically tractable model organism. Here we show that two nematode
      species namely Steinernema feltiae and Heterorhabditis bacteriophora display
      different infectivity toward Drosophila larvae with the latter being less
      pathogenic. The effects of supporting media and IJ dosage on the mortality of the
      hosts were assessed and optimized. Using optimum conditions, a faster and
      efficient setup for nematode infections was developed. This newly established
      infection model in Drosophila larvae will be applicable in large scale screens
      aimed at identifying novel genes/pathways involved in innate immune responses.

PMID- 22614786
TI  - An information theory analysis of gene-environmental interactions in count/rate
      data.
AB  - OBJECTIVE: To develop and critically evaluate an information theory method for
      identifying gene-gene and gene-environment interactions in count and rate data.
      METHODS: The entropy-based metric k-way interaction information (KWII) was
      critically assessed for utility in detecting interactions with count data and
      over-dispersed count data in three simulation studies of increasing complexity
      and in datasets from animal models of depression and colitis. The results were
      compared to Poisson regression. The power and effect size dependence of the KWII
      for detecting interactions was also assessed. RESULTS: The KWII was capable of
      effectively identifying the genetic and environmental predictors and their
      interactions in all three simulated datasets. The results indicate that the KWII
      approach may produce more parsimonious results than regression. In a rat model of
      depression, we successfully identified a prominent gender effect as well as other
      published associations. Analysis of severity scores from an animal model of
      colitis identified markers from chromosome 3, as well as unique first- and second
      order associations for the individual sections of the colon and cecum.
      CONCLUSIONS: The results demonstrate the utility and versatility of our entropy
      based method for gene-environment interaction analysis of count and rate data
      with Poisson and over-dispersed distributions.

PMID- 22614787
TI  - Therapy: An extended-release form of cysteamine bitartrate for cystinosis.

PMID- 22614788
TI  - Hemodialysis: Fish oil for hemodialysis.

PMID- 22614790
TI  - Assessment of kidney function: Novel biomarkers associated with kidney function
      decline.

PMID- 22614789
TI  - The immunoregulatory function of vitamin D: implications in chronic kidney
      disease.
AB  - Cardiovascular and infectious diseases remain the most common causes of death
      among patients with chronic kidney disease (CKD) and end-stage renal disease
      (ESRD). Basic science and epidemiological studies indicate that vitamin D has
      importance not only for cardiovascular health, but also for the immune response.
      Vitamin D signaling pathways regulate both innate and adaptive immunity,
      maintaining the associated inflammatory response within physiological limits.
      Levels of both the inactive as well as active form of vitamin D (25
      hydroxyvitamin D and 1,25-dihydroxyvitamin D, respectively) are decreased in
      patients with CKD and ESRD. It is reasonable to hypothesize, therefore, that the
      immune dysfunction associated with vitamin D deficiency in patients with CKD and
      ESRD in part explains the misdirected inflammatory response and increased
      susceptibility to infection seen in this population. Indeed, observational
      studies show that vitamin D deficiency in patients with ESRD is associated with
      increased mortality, and treatment with vitamin D is associated with a decreased
      risk of infection, as well as reduced all-cause mortality. However, whether
      different vitamin D preparations have differential effects on physiological
      function and clinical outcomes is still unclear. A proper understanding of the
      immune regulatory function of vitamin D is important for the development of
      future therapeutic strategies.

PMID- 22614791
TI  - Limited sampling strategies to estimate the area under the concentration-time
      curve. Biases and a proposed more accurate method.
AB  - BACKGROUND: Over 100 limited sampling strategies (LSSs) have been proposed to
      reduce the number of blood samples necessary to estimate the area under the
      concentration-time curve (AUC). The conditions under which these strategies
      succeed or fail remain to be clarified. OBJECTIVES: We investigated the accuracy
      of existing LSSs both theoretically and numerically by Monte Carlo simulation. We
      also proposed two new methods for more accurate AUC estimations. METHODS: We
      evaluated the following existing methods theoretically: i) nonlinear curve
      fitting algorithm (NLF), ii) the trapezium rule with exponential curve
      approximation (TZE), and iii) multiple linear regression (MLR). Taking busulfan
      (BU) as a test drug, we generated a set of theoretical concentration-time curves
      based on the identified distribution of pharmacokinetic parameters of BU and re
      evaluated the existing LSSs using these virtual validation profiles. Based on the
      evaluation results, we improved the TZE so that unrealistic parameter values were
      not used. We also proposed a new estimation method in which the most likely curve
      was selected from a set of pre-generated theoretical concentration-time curves.
      RESULTS: Our evaluation, based on clinical profiles and a virtual validation set,
      revealed: i) NLF sometimes overestimated the absorption rate constant Ka, ii) TZE
      overestimated AUC over 280% when Ka is small, and iii) MLR underestimated AUC
      over 30% when the elimination rate constant Ke is small. These results were
      consistent with our mathematical evaluations for these methods. In contrast, our
      two new methods had little bias and good precision. CONCLUSIONS: Our
      investigation revealed that existing LSSs induce different but specific biases in
      the estimation of AUC. Our two new LSSs, a modified TZE and one using model
      concentration-time curves, provided accurate and precise estimations of AUC.

PMID- 22614792
TI  - Primary care referral of patients with low back pain to physical therapy: impact
      on future health care utilization and costs.
AB  - STUDY DESIGN: A retrospective cohort. OBJECTIVE: To describe physical therapy
      utilization following primary care consultation for low back pain (LBP) and
      evaluate associations between the timing and content of physical therapy and
      subsequent health care utilization and costs. SUMMARY OF BACKGROUND DATA: Primary
      care management of LBP is highly variable and the implications for subsequent
      costs are not well understood. The importance of referring patients from primary
      care to physical therapy has been debated, and information on how the timing and
      content of physical therapy impact subsequent costs and utilization is needed.
      METHODS: Data were extracted from a national database of employer-sponsored
      health plans. A total of 32,070 patients with a new primary care LBP consultation
      were identified and categorized on the basis of the use of physical therapy
      within 90 days. Patients utilizing physical therapy were further categorized
      based on timing (early [within 14 d] or delayed)] and content (guideline adherent
      or nonadherent). LBP-related health care costs and utilization in the 18-months
      following primary care consultation were examined. RESULTS: Physical therapy
      utilization was 7.0% with significant geographic variability. Early physical
      therapy timing was associated with decreased risk of advanced imaging (odds ratio
      [OR] = 0.34, 95% confidence interval [CI]: 0.29, 0.41), additional physician
      visits (OR = 0.26, 95% CI: 0.21, 0.32), surgery (OR = 0.45, 95% CI: 0.32, 0.64),
      injections (OR = 0.42, 95% CI: 0.32, 0.64), and opioid medications (OR = 0.78,
      95% CI: 0.66, 0.93) compared with delayed physical therapy. Total medical costs
      for LBP were $2736.23 lower (95% CI: 1810.67, 3661.78) for patients receiving
      early physical therapy. Physical therapy content showed weaker associations with
      subsequent care. CONCLUSION: Early physical therapy following a new primary care
      consultation was associated with reduced risk of subsequent health care compared
      with delayed physical therapy. Further research is needed to clarify exactly
      which patients with LBP should be referred to physical therapy; however, if
      referral is to be made, delaying the initiation of physical therapy may increase
      risk for additional health care consumption and costs.

PMID- 22614794
TI  - Effect of multilevel open-door laminoplasty and laminectomy on flexibility of the
      cervical spine: an experimental investigation.
AB  - STUDY DESIGN: A biomechanical comparison of 2 commonly used posterior surgical
      procedures for spinal cord decompression in the cervical spine: laminoplasty
      (open door) and laminectomy. OBJECTIVE: To delineate differences in cervical
      motion after laminoplasty (2-level and multilevel) and laminectomy. SUMMARY OF
      BACKGROUND DATA: Cervical spondylotic myelopathy is a common spinal cord disorder
      in persons aged 55 years or older. Laminectomy and laminoplasty are the 2 common
      posterior-based techniques used for decompression of spinal cord. There is lack
      of adequate literature data on the intersegmental rotations at the operated and
      adjacent levels. METHODS: Five human cadaveric specimens were tested sequentially
      as follows: (1) intact, (2) laminoplasty at C5-C6, (3) laminoplasty at C3-C6, and
      (4) laminectomy at C3-C6, each subjected to 2 N.m moments in flexion/extension,
      right/left lateral bending, and right/left axial rotation. For laminoplasty, the
      laminae of the involved vertebrae were stabilized with standard 10-mm plates and
      screws. The total and segmental motions of the specimens were measured before and
      after the surgical procedures. Statistical analysis was performed using repeated
      measures analysis of variance, with P < 0.05 as the level of significance.
      RESULTS: Two-level laminoplasty led to minimal decrease (<7% in the 3 loading
      modes) in C2-T1 motion. Multilevel laminoplasty resulted in a minimal increase
      during lateral bending (4%) and axial rotation (6%). During flexion/extension,
      both C4-C5 and C2-C3 showed a decrease of 20% (P > 0.05) and 17% (P > 0.05) after
      2-level and multilevel laminoplasty, respectively. Laminectomy resulted in a
      statistically significant (P < 0.05) increase in the C2-T1 range of motion
      compared with the intact condition during the 3 loading modes (21% in
      flexion/extension, 8% in lateral bending, and 15% in axial rotation). CONCLUSION:
      Both 2-level and multilevel laminoplasty preserved the C2-T1 range of motion.
      Laminectomy resulted in a significant increase in C2-T1 motion due to the loss of
      the posterior structures.

PMID- 22614793
TI  - Does obesity affect outcomes of treatment for lumbar stenosis and degenerative
      spondylolisthesis? Analysis of the Spine Patient Outcomes Research Trial (SPORT).
AB  - STUDY DESIGN: Retrospective subgroup analysis of prospectively collected data
      according to treatment received. OBJECTIVE: The purpose of this study was to
      determine whether obesity affects treatment outcomes for lumbar stenosis (SpS)
      and degenerative spondylolisthesis (DS). SUMMARY OF BACKGROUND DATA: Obesity is
      thought to be associated with increased complications and potentially less
      favorable outcomes after the treatment of degenerative conditions of the lumbar
      spine. This, however, remains a matter of debate in the existing literature.
      METHODS: An as-treated analysis was performed on patients enrolled in the Spine
      Patient Outcomes Research Trial for the treatment of SpS or DS. A comparison was
      made between patients with a body mass index (BMI) of less than 30 ("nonobese," n
      = 373 SpS and 376 DS) and those with a BMI of 30 or more ("obese," n = 261 SpS
      and 225 DS). Baseline patient characteristics, intraoperative data, and
      complications were documented. Primary and secondary outcomes were measured at
      baseline and regular follow-up time intervals up to 4 years. The difference in
      improvement over baseline between surgical and nonsurgical treatment (i.e.,
      treatment effect) was determined at each follow-up interval for the obese and
      nonobese groups. RESULTS: At 4-year follow-up, operative and nonoperative
      treatment provided improvement in all primary outcome measures over baseline in
      patients with BMI of less than 30 and 30 or more. For patients with SpS, there
      were no differences in the surgical complication or reoperation rates between
      groups. Patients with DS with BMI of 30 or more had a higher postoperative
      infection rate (5% vs. 1%, P = 0.05) and twice the reoperation rate at 4-year
      follow-up (20% vs. 11%, P = 0.01) than those with BMI of less than 30. At 4
      years, surgical treatment of SpS and DS was equally effective in both BMI groups
      in terms of the primary outcome measures, with the exception that obese patients
      with DS had less improvement from baseline in the 36-Item Short Form Health
      Survey (SF-36) physical function score than nonobese patients (22.6 vs. 27.9, P =
      0.022). With nonoperative treatment, patients with SpS with BMI of 30 or more did
      worse in regard to all 3 primary outcome measures, and patients with DS with BMI
      of 30 or more had similar SF-36 bodily pain scores but less improvement over
      baseline in the SF-36 physical function and Oswestry Disability Index scores.
      Treatment effects for SpS and DS were significant within each BMI group for all
      primary outcome measures in favor of surgery. Obese patients had a significantly
      greater treatment effect than nonobese patients with SpS (Oswestry Disability
      Index, P = 0.037) and DS (SF-36 PF, P = 0.004) largely due to the relatively poor
      outcome of nonoperative treatment in obese patients. CONCLUSION: Obesity does not
      affect the clinical outcome of operative treatment of SpS. There are higher rates
      of infection and reoperation and less improvement from baseline in the SF-36
      physical function score in obese patients after surgery for DS. Nonoperative
      treatment may not be as effective in obese patients with SpS or DS.

PMID- 22614795
TI  - Outcomes at 12 months after early magnetic resonance imaging in acute trauma
      patients with persistent midline cervical tenderness and negative computed
      tomography.
AB  - STUDY DESIGN: A prospective observational cohort study of alert, neurologically
      intact trauma patients presenting to the emergency department with midline
      cervical tenderness. Screening cervical magnetic resonance imaging (MRI) had been
      conducted after negative computed tomography (CT) when tenderness was persistent.
      OBJECTIVE: To determine the association of acute findings and demographic
      characteristics with any long-term neck disability, and with time to return to
      work in such patients. SUMMARY OF BACKGROUND DATA: The relationship between acute
      findings and outcomes in these patients is unknown, and we hypothesized that
      outcomes at 12 months would correlate with acute clinical signs and symptoms, MRI
      findings, and mechanisms of injury. METHODS: Patients at a Level 1 trauma center
      with persistent midline cervical tenderness in the absence of evidence of
      intoxication, painful distracting injury, persistently abnormal neurology, or
      acute CT findings, who underwent early cervical MRI under the institutional
      protocol, were reviewed in the outpatient spine clinic after discharge. In
      addition, the factors associated with neck disability and time to return to work
      were examined at follow-up at 12 months after presentation. RESULTS: There were
      162 of 178 patients available for follow-up at 12 months (91%). Of these, 46% had
      MRI-identified cervical spine injury at their initial examination, and 22% had
      required clinical management, including 2.5% with operative stabilization. Neck
      disability was present in 43% of patients and was associated with depressive
      symptoms, workers' compensation, and low annual income. Delay in return to work
      was associated with the presence of minor limb/other fractures and depressive
      symptoms, whereas patients on high annual incomes were found to return to work
      more quickly. CONCLUSION: Surprisingly in these acute trauma patients, MRI
      detected injury, clinical factors, and injury mechanism were not found to be
      associated with long-term patient outcomes. As a result, a trial of a more
      targeted, individual return to work plan, including strategies aimed at improving
      physical and psychological function, may now be justified to optimize long-term
      recovery, reduce health resource costs, and maximize economic productivity
      through early return to work.

PMID- 22614796
TI  - Intraoperative decrease in amplitude of somatosensory-evoked potentials of the
      lower extremities with interbody fusion cage placement during lumbar fusion
      surgery.
AB  - STUDY DESIGN: A retrospective analysis was performed. OBJECTIVE: To characterize
      neurophysiological data of patients who had a decrease in amplitude of
      somatosensory-evoked potentials (SSEP) of the lower extremities secondary to
      interbody fusion cage placement during lumbar fusion surgery with no alert of the
      electromyography (EMG). SUMMARY OF BACKGROUND DATA: The most consistently used
      and studied modalities of neurophysiological monitoring during spine surgery are
      SSEPs, motor-evoked potentials (MEPs), and EMG. In general, it is accepted that
      MEPs along with SSEPs are used to detect spinal cord injury and EMGs are used to
      detect nerve root injury. METHODS: The medical records of a consecutive series of
      115 patients who had undergone a transforaminal lumbar interbody fusion (TLIF)
      procedure in which SSEPs, MEPs, and EMGs were utilized for neurophysiological
      monitoring were retrospectively reviewed. RESULTS: One hundred fifteen cases of
      TLIF procedures were reviewed. The follow-up was 2 years after the last
      procedure. A total of 5 cases that demonstrated intraoperative SSEP changes were
      found. The age range for these cases was from 39 to 81 years (mean age, 61 yr).
      All 5 patients developed SSEP changes that were secondary to interbody fusion
      cage placement. All 5 cases demonstrated reversal of the SSEP changes to baseline
      after removal of the interbody cage. Three of these cases had no new
      postoperative neurological findings. However, given that these 3 cases of SSEP
      change were associated with a surgical event that improved secondary to an
      intervention (in this case removal of the interbody cage), those cases were
      classified as presumed positive. Two of the 5 cases were in fact associated with
      a new postoperative neurological deficit. CONCLUSION: To our knowledge this study
      demonstrates the first reported SSEP alerts that were associated with a posterior
      lumbar interbody cage placement without a corresponding EMG alert.

PMID- 22614797
TI  - Comparison of the amounts of canal encroachment between semisitting and supine
      position of computed tomography-myelography for vertebral fractures of the
      elderly involving the posterior vertebral wall.
AB  - STUDY DESIGN: A prospective radiographical trial. OBJECTIVE: To elucidate effects
      of loading associated with spinal canal encroachment (SCE) in patients with
      insufficient bone union after vertebral fractures in the elderly, using computed
      tomography-myelography in 2 different positions. SUMMARY OF BACKGROUND DATA: In
      elderly patients with vertebral fractures, influence of loading would be involved
      in SCE, but the details are not well understood. METHODS: Seventeen patients
      (mean age, 77.4 +/- 8 yr; range, 62-91 yr) with various degrees of neurological
      deficit due to insufficient bone union at both vertebral body and posterior
      vertebral wall were included in this study. Computed tomography-myelography was
      performed in both semisitting and supine positions. Kyphotic angle, rate of dural
      compression, ratio of occupation by bony fragments, and posterior vertebral body
      height ratio were measured and compared between positions. RESULTS: Mean ratio of
      occupation by bony fragments was significantly higher in the semisitting position
      (47.9 +/- 9.2%) than in the supine position (33.9 +/- 10.0%, P, 0.001).
      Similarly, mean posterior vertebral body height ratio was significantly lower in
      the semisitting position (67.8 +/- 10.8%) than in the supine position (76.3 +/-
      13.3%), indicating a significant loss of vertebral height in the semisitting
      position (P, 0.001). Mean rate of dural compression was likewise significantly
      higher in the semisitting position (48.6 +/- 13.3%) than in the supine position
      (33.3 +/- 16.5%; P, 0.001). Mean change in ratio of occupation by bony fragments,
      change in posterior vertebral body height ratio, and angular instability between
      positions were 13.9 +/- 8.6%, 8.5 +/- 6.7%, and 13 degrees  +/- 5.7 degrees ,
      respectively. A significant correlation was identified between change in ratio of
      occupation by bony fragments and change in posterior vertebral body height ratio
      (P = 0.001). CONCLUSION: Our study demonstrated that collapse of the nonunited
      posterior vertebral wall and intracanal protrusion of vertebral fragments would
      occur simultaneously with axial loading, causing SCE. Computed tomographic scan
      obtained in semisitting position seems quite useful to evaluate the amount of SCE
      by an unstable posterior wall.

PMID- 22614798
TI  - Does ScoliScore provide more information than traditional clinical estimates of
      curve progression?
AB  - STUDY DESIGN: Retrospective study comparing ScoliScore and clinical risk
      estimates. OBJECTIVE: The purpose of this study was to compare risk
      stratification between ScoliScore and traditional clinical estimates to determine
      whether ScoliScore provides unique information. SUMMARY OF BACKGROUND DATA:
      ScoliScore is a genetic prognostic test designed to evaluate the risk of curve
      progression in skeletally immature patients with adolescent idiopathic scoliosis
      with Cobb angles of 10 degrees  to 25 degrees . Clinicians are currently trying
      to better understand the role this test may play in guiding clinical decision
      making because current standards of curve progression are largely based on
      radiographical markers, such as curve magnitude and bone age. METHODS: Ninety-one
      patients who received ScoliScore testing at our center and met study inclusion
      criteria were identified. Patients were given a "clinical risk" level using their
      Risser sign and Cobb angle. Assigned clinical risk levels were compared with the
      ScoliScore risk levels reported by the manufacturer's scoring algorithm. RESULTS:
      ScoliScore risk distribution in our population was 36% low risk, 55% intermediate
      risk, and 9% high risk. This compares with 2%, 51%, and 47%, respectively, for
      comparable clinical risk groupings. Only 25% of patients were in the same risk
      category for both systems. There were no significant correlations between
      ScoliScore and age, race, menarcheal status, Risser sign, or sex. There was a
      positive correlation between the Cobb angle and the ScoliScore (r = 0.581, P <
      0.001). Cobb angle remained significant in the multivariate regression model (P <
      0.001), and Cobb angle was found to account for 33.3% of ScoliScore's variance.
      CONCLUSION: Only Cobb angle showed significant correlation with ScoliScore among
      the socioclinical variables studied. The risk distribution of the 2 risk
      estimation systems examined differed markedly: ScoliScore predicted nearly 16
      times more low-risk patients and more than 5 times fewer high-risk patients. This
      demonstrates that ScoliScore provides unique information to traditional
      predictors of curve progression, advancing our understanding of the role of
      ScoliScore in the clinical setting.

PMID- 22614799
TI  - What is the best way to optimize thoracic kyphosis correction? A micro-CT and
      biomechanical analysis of pedicle morphology and screw failure.
AB  - STUDY DESIGN: A human cadaveric biomechanical analysis. OBJECTIVE: The purpose of
      this study was to evaluate the bone density/trabecular width of the thoracic
      pedicle and correlate that with its resistance against compressive loading used
      during correction maneuvers in the thoracic spine (i.e., cantilever bending).
      SUMMARY OF BACKGROUND DATA: As surgeons perform cantilever correction maneuvers
      in the spine, it is common to have pedicle screws pullout or displace while
      placing corrective forces on the construct. Currently, surgeons either compress
      against the cephalad aspect of the pedicle or vice versa. We set out to establish
      which aspect of the pedicle was the most dense and to determine the optimal
      direction for screw compression during kyphosis/deformity correction. METHODS:
      Fifteen fresh-frozen cadaveric vertebrae (n = 15) were examined by micro-computed
      tomography to determine percent bone volume/total volume (%BV/TV) within the
      cephalad and caudad aspects of the pedicle. Specimens were sectioned in the
      sagittal plane. Pedicles were instrumented according to the straightforward
      trajectory on both sides. Specimens were then mounted and loading to failure was
      performed perpendicular to the screw axis (either the cephalad or the caudad
      aspect of the pedicle). RESULTS: Mean failure when loading against the caudad
      aspect of the pedicle was statistically, significantly greater (454.5 +/- 241.3 N
      vs. 334.79 1 +/- 158.435 N) than for the cephalad pedicle (P < 0.001). In
      concordance with failure data, more trabecular and cortical bones were observed
      within the caudad half of the pedicle compared with the cephalad half (P <
      0.001). CONCLUSION: Our results suggest that the caudad half of the pedicle is
      denser and withstands higher forces compared with the cephalad aspect. In turn,
      the incidence of intraoperative screw loosening and/or pedicle fracture may be
      reduced if the compressive forces (cantilever bending during deformity
      correction) placed upon the construct are applied against the caudad portion of
      the pedicle.

PMID- 22614800
TI  - Risk factors for heterotopic ossification in patients with spinal cord injury: a
      case-control study of 264 patients.
AB  - STUDY DESIGN: Case-control study. OBJECTIVE: We designed a case-control study to
      analyze the risk factors associated with the development of heterotopic
      ossification (HO) in patients with traumatic spinal cord injury. SUMMARY OF
      BACKGROUND DATA: Patients with spinal cord injury have a high risk of developing
      HO, although the exact etiopathogenesis is still unknown. Several factors are
      known to be potential risk factors. However, we are not aware of any large
      clinical studies evaluating the risk factors for HO. METHODS: Patients who were
      treated for a traumatic spinal cord injury in our hospital, and who subsequently
      developed HO, were identified by querying the electronic database at our hospital
      from 2002 to 2010. One hundred thirty-two patients and 132 controls were
      included. Our primary outcome measures were the risk of developing HO according
      to whether the patient had experienced a complete spinal cord lesion according to
      American Spinal Injury Association Impairment Scale; tetraplegia or paraplegia;
      cervical, thoracic, or lumbar injury; severe chest trauma; and the time interval
      between injury and surgery. Secondary risk factors explored were patient age;
      sex; presence and number of comorbidities; length of hospital and intensive care
      unit stay; associated traumatic injuries; presence of spasticity, pressure
      ulcers, deep venous thrombosis, and urinary tract infection; and pulmonary
      complications, such as pneumonia and necessity of tracheostomy. RESULTS: Patients
      with associated spasticity and thoracic trauma, complete lesion, pneumonia,
      presence of tracheostomy, and urinary tract infection had a higher risk of
      developing HO. CONCLUSION: Adequate management of potential risk factors could
      help reduce the overall incidence of HO and outcome in patients with traumatic
      spinal cord injury.

PMID- 22614801
TI  - Anterior decompression and nonstructural bone grafting and posterior fixation for
      cervical facet dislocation with traumatic disc herniation.
AB  - STUDY DESIGN: A series study of patients with lower cervical facet dislocation
      accompanied by traumatic disc herniation treated with anterior decompression and
      nonstructural bone grafting and posterior fixation. OBJECTIVE: To describe a
      surgical technique of anterior decompression and nonstructural bone grafting and
      posterior fixation and its clinical outcome in a group of patients with lower
      cervical facet dislocation accompanied by traumatic disc herniation. SUMMARY OF
      BACKGROUND DATA: The optimal treatment for lower cervical facet dislocation with
      a prolapsed disc is still controversial. METHODS: After discectomy and endplate
      preparation, a layer of morselized cancellous bone grafts from the iliac crest
      was placed in the interspace, and held in appropriate sagittal position by 2
      layers of gelatin sponge and carefully sutured longus colli muscle. The anterior
      wound was then closed. The posterior elements were exposed and the reduction was
      performed. Fluoroscopy was used during reduction maneuver to ensure that the
      graft was still in the appropriate position. A posterior fusion was performed and
      the posterior wound was closed. RESULTS: Between January 2006 and February 2010,
      21 patients with cervical facet dislocation accompanied by traumatic disc
      herniation (13 unilateral dislocations and 8 bilateral dislocations) were
      recruited for this study. All the patients completed at least 1-year follow-up.
      Average follow-up duration was 29 +/- 3.5 months. Average Frankel scales were
      significantly improved at the end of follow-up, visual analogue scale decreased
      from 7.8 +/- 1.2 before the operation to less than 1.6 +/- 0.5 (P < 0.05) 6
      months later. Kyposis was corrected from 17.7 degrees  +/- 6.3 degrees  to 6.5
      degrees  +/- 4.1 degrees  (P < 0.05) and remained at 5.9 degrees  +/- 4.2 degrees
      (P > 0.05) 1 year later. The average subsidence of bone graft was 1.28 +/- 0.16
      mm at 12 months after the operation and remained 1.34 +/- 0.20 mm at 36 months
      after the operation. All patients had consolidation of both anterior and
      posterior fusions. No cases of instrument failure occurred and no complications
      were attributed to the use of this technique. CONCLUSION: Although further study
      based on injury types as well as long-term follow-up is still needed, anterior
      decompression and nonstructural bone grafting and posterior fixation provides a
      promising surgical option for treating cervical facet dislocation with traumatic
      disc herniation.

PMID- 22614802
TI  - Validity and reliability of the metric measurements in the assessment of lumbar
      spine motion in patients with ankylosing spondylitis.
AB  - STUDY DESIGN: A prospective, controlled clinical study performed in a tertiary
      care center. OBJECTIVE: To determine reliability and validity of low-tech
      measurements in assessment of range of motion (ROM) of lumbar flexion in
      ankylosing spondylitis (AS). SUMMARY OF BACKGROUND DATA: ROM measurements of
      lumbar flexion in patients with AS and healthy subjects are evaluated using
      original Schober test (OST), modified Schober index (MSI), and modified-modified
      Schober test (MMST) and compared with radiography. METHODS: Fifty patients with
      AS and 17 healthy subjects were included. A tape measure was used for measuring
      OST, MSI, and MMST, and goniometer was used for measuring angle of lumbar ROM on
      lateral radiographical views in erect position and maximal forward bending
      position. RESULTS: Angle between L1 and S1 vertebrae displayed a change upon
      flexion by 18.2 degrees  +/- 18.7 degrees  in AS group and 30.4 degrees  +/- 11.1
      degrees  in controls (P = 0.002). Angle between L3 and S1 vertebrae was detected
      to change upon flexion by 25.3 degrees  +/- 25.4 degrees  in AS group and 46.7
      degrees  +/- 14.2 degrees  in controls (P = 0.0001). A weak correlation was
      observed between MSI, OST, and L1-S1 radiographical mobility measurements as (P =
      0.018 and P = 0.063) and MSI, OST, and L3-S1 radiographical mobility measurements
      as (P = 0.009 and P = 0.024), respectively for AS. There were correlations
      between MSI, OST, and radiographical mobility measurements in patients with AS (r
      = 0.333, P = 0.018, and r = 0.363, P = 0.009, respectively). There was a
      correlation between OST and radiographical mobility measurements in controls (r =
      -0.504, P = 0.039). Intrarater reliability was determined to be excellent for
      OST, MSI, and MMST. CONCLUSION: Despite excellent intrarater reliabilities for
      OST, MSI, and MMST, only a weak correlation could be established between OST,
      MSI, and MMST and radiographical analysis. MMST was found not to reflect lumbar
      spine angular motions. Although MSI reflected spinal mobility better than OST,
      both seemed to reflect lumbar spine angular motion poorly.

PMID- 22614803
TI  - Antiphospholipid antibody profiling: association with the clinical phenotype of
      antiphospholipid syndrome? Comment on the article by Otomo et al.

PMID- 22614804
TI  - Solar energy conversion with tunable plasmonic nanostructures for thermoelectric
      devices.
AB  - The photothermal effect in localized surface plasmon resonance (LSPR) should be
      fully utilized when integrating plasmonics into solar technologies for improved
      light absorption. In this communication, we demonstrate that the photothermal
      effect of silver nanostructures can provide a heat source for thermoelectric
      devices for the first time. The plasmonic band of silver nanostructures can be
      facilely manoeuvred by tailoring their shapes, enabling them to interact with
      photons in different spectral ranges for the efficient utilization of solar
      light. It is anticipated that this concept can be extended to design a
      photovoltaic-thermoelectric tandem cell structure with plasmonics as mediation
      for light harvesting.

PMID- 22614805
TI  - TGF-beta of lung cancer microenvironment upregulates B7H1 and GITRL expression in
      dendritic cells and is associated with regulatory T cell generation.
AB  - The effects of TGF-beta on dendritic cells (DCs) on the tumor microenvironment
      are not well understood. We report, here, the establishment of an in vitro lung
      cancer microenvironment by co-incubation of seminaphtharhodafluor (SNARF) labeled
      Lewis lung cancer (LLC) cells, carboxyfluorescein succinimidyl ester (CFSE)
      labeled fibroblasts and 4-chloromethyl-7-hydroxycoumarin (CMHC) labeled DCs. Raw
      264.7, EL4 and NCI-H446 cells were able to synthesize TGF-beta which was
      determined by flow cyto-metry and western blotting, respectively. Furthermore,
      TGF-beta efficiently increased regulatory T-cell (Treg) expansion and upregulated
      DC B7H1 and GITRL expression. TGF-beta and the co-incubation of LLC cells,
      fibroblasts with DCs could augment the expression of B7H1 and GITRL molecules of
      DCs. The data presented here indicate that the B7H1 and GITRL molecules may play
      an important role in TGF-beta-induced Treg expansion of lung cancer
      microenvironment.

PMID- 22614806
TI  - Neuroanatomical correlates of tinnitus revealed by cortical thickness analysis
      and diffusion tensor imaging.
AB  - INTRODUCTION: Tinnitus is a poorly understood auditory perception of sound in the
      absence of external stimuli. Convergent evidence proposes that tinnitus
      perception involves brain structural alterations as part of its pathophysiology.
      The aim of this study is to investigate the structural brain changes that might
      be associated with tinnitus-related stress and negative emotions. METHODS: Using
      high-resolution magnetic resonance imaging and diffusion tensor imaging, we
      investigated grey matter and white matter (WM) alterations by estimating cortical
      thickness measures, fractional anisotropy and mean diffusivity in 14 tinnitus
      subjects and 14 age- and sex-matched non-tinnitus subjects. RESULTS: Significant
      cortical thickness reductions were found in the prefrontal cortex (PFC), temporal
      lobe and limbic system in tinnitus subjects compared to non-tinnitus subjects.
      Tinnitus sufferers were found to have disrupted WM integrity in tracts involving
      connectivity of the PFC, temporal lobe, thalamus and limbic system. CONCLUSION:
      Our results suggest that such neural changes may represent neural origins for
      tinnitus or consequences of tinnitus and its associations.

PMID- 22614808
TI  - Comparison of the intraoral and transcervical approach in submandibular gland
      excision.
AB  - The purpose of this study is to evaluate the benefits of the intraoral approach
      for removal of the submandibular gland (SMG) by comparing it with the usual
      method of the transcervical approach. Sixteen patients who required SMG resection
      for benign disorders were divided into two surgical groups who underwent surgery
      via the intraoral (n = 8) or transcervical (n = 8) approach. The intraoral
      approach (IOA) consisted of an incision on the floor of mouth from the caruncle
      of Wharton's duct to the retromolar trigone while the transcervical approach
      (TCA) consisted of an incision along the natural skin crease overlying the gland.
      The operation time, hospital stay, complications, and cosmetic appearance were
      compared between groups. The mean operation time of the IOA group was
      significantly longer than that of the TCA group, but decreased gradually with
      surgical experience. The mean hospital stay of the IOA group was significantly
      shorter than that of the TCA group. Most patients (88 %) of the IOA group
      experienced sensory defects of the lingual nerve, but these symptoms were
      temporary. No lasting complications were noted in the IOA group; however, one
      patient of the TCA group had permanent paralysis of the marginal mandibular
      branch of the facial nerve. The incision scars were invisible owing to the
      location on the mouth floor in the IOA group, whereas they were apparent even on
      the natural skin crease of the neck in the TCA group. In conclusion, the SMG can
      be removed safely and effectively by IOA with the avoidance of an external scar
      and of injury to the marginal mandibular nerve. We suggest that the IOA be
      substituted for the TCA as the primary procedure for removal of the SMG in
      suitably selected patients.

PMID- 22614807
TI  - The posterior glottis: structural and clinical considerations.
AB  - Despite the presence of a number of good publications during the past two
      decades, the posterior glottis (PG) is still not clearly appreciated in clinical
      laryngological practice. This study focuses on searching the literature to find
      out the present day awareness of the PG, as well as highlighting some of its
      clinical features. The investigation proceeds with two main sections: (1)
      critical analysis of the literature on the PG during the last 50 years (2)
      describing the clinical appearance and behavior of the PG in 100 normal subjects.
      Results of section 1 illustrate the limited awareness in the literature of the
      existence of PG as a distinct part of the human larynx. Results of section 2
      illustrate some misconcepts related to the PG as inter-arytenoid pachydermia,
      change of voice with lesions in the PG. Discussion elaborates on the significance
      of the findings and attempts to clarify certain misconcepts about the PG, its
      structure, function, and clinical features. In the light of the data collected
      from the literature regarding the dimensions of the PG, a set of recommendations
      were proposed regarding the optimal sizes of the endotracheal tubes in both
      sexes.

PMID- 22614809
TI  - Visualizing results from infection transmission models: a case against
      "confidence intervals".
AB  - Stochastic transmission models are highly important in infectious disease
      epidemiology. The quantity of data produced by these models is challenging to
      display and communicate. A common approach is to display the model results in the
      familiar form of a mean or median and 95% interval, plotted over time. This
      approach has drawbacks, however, including the potential for ambiguity and
      misinterpretation of model results. Instead, we propose 2 alternative approaches
      for visualizing results from stochastic models. These proposed approaches convey
      the information provided by the median and 95% interval, as well as information
      about unexpected outcomes that may be of particular interest for stochastic
      epidemic models.

PMID- 22614810
TI  - Isolation and characterization of a novel filamentous phage from Stenotrophomonas
      maltophilia.
AB  - In this study, a novel filamentous phage, phiSHP1, of the environmental
      Stenotrophomonas maltophilia strain P2 was isolated and characterized. Electron
      microscopy showed that phiSHP1 resembled members of the family Inoviridae and was
      about 2.1 MUm long. The 6,867-nucleotide genome of phiSHP1 was a circular single
      stranded DNA and had a replication form designated pSH1. Ten putative open
      reading frames (ORFs) were found in the phiSHP1 genome, and six predicted
      proteins showed similarity to proteins in databases. Tricine sodium dodecyl
      sulfate polyacrylamide gel electrophoresis of phiSHP1 displayed one major
      structural polypeptide of approximately 4.0 kDa. N-terminal sequencing showed
      that it was the mature product of ORF5 and that its N-terminal 27 amino acid
      residues had been cleaved off from the predicted nascent protein. Finally,
      phylogenetic trees were constructed to analyze the phylogenetic relationship of
      phiSHP1 to other known filamentous phages. phiSHP1 appears to be the first
      reported Stenotrophomonas filamentous phage.

PMID- 22614811
TI  - Complete nucleotide sequence of a new strain of grapevine leafroll-associated
      virus 3 in South Africa.
AB  - The complete genome sequences of two newly identified genetic variants of
      grapevine leafroll-associated virus 3 (GLRaV-3) are described. Two isolates, GH11
      (18671 nt) and GH30 (18576 nt) were sequenced and found to be less than 70 %
      similar to other South African GLRaV-3 variants. The genome organization of GH11
      and GH30 is similar to that of previously described GLRaV-3 isolates. However, no
      corresponding open reading frame 2 (ORF2) could be identified. Phylogenetic
      analysis indicates that GH11 and GH30 cluster in a subgroup (group VI) that is
      separate from the previously described GLRaV-3 isolates and should be regarded as
      a different strain of GLRaV-3.

PMID- 22614812
TI  - Detection of human bocaviruses 1, 2 and 3 in Irish children presenting with
      gastroenteritis.
AB  - Human bocavirus has been increasingly detected worldwide in patients suffering
      from gastroenteritis, with the highest incidence reported in children aged
      between 6 and 24 months. A total of 155 non-bacterial gastroenteritis samples
      consisting of rotavirus-, adenovirus- and norovirus-positive specimens were
      collected from patients in the Munster region of Ireland from 2006-2008. Of these
      155, a total of 12 were positive for the presence of human bocavirus. Three types
      of human bocavirus were identified: HBoV1, 2 and 3. In addition, recombinant
      strains (n=4) were also isolated. This is the first report of all three types of
      HBoV being detected in southern Ireland.

PMID- 22614813
TI  - Nutrigenetics. The speed of progress.

PMID- 22614814
TI  - Genetic variations in polyunsaturated fatty acid metabolism--implications for
      child health?
AB  - Sufficient nutritional supply with polyunsaturated fatty acids (PUFAs) has long
      been considered as beneficial for child health, especially in regard to neuronal
      development and allergic diseases. In recent years, genetic association studies
      showed that in addition to nutritional influences, the genetic background is
      highly important for PUFA composition in human tissues. Specifically,
      polymorphisms in the fatty acid desaturase genes or FADS determine the efficiency
      of how PUFAs are processed endogenously. Recent gene-nutrition interaction
      studies suggest that these polymorphisms modulate the effect of nutritional fatty
      acid intake on complex phenotypes such as cognitive outcomes and asthma risk in
      children. These early results may provide the basis for future well-specified
      dietary recommendations to achieve optimal health benefit for all children. This
      article presents results from recent gene-nutrition interaction studies,
      discusses its implications for child health, and gives an outlook how this
      association might translate into clinical practice in the future.

PMID- 22614815
TI  - Diet-gene interactions underlie metabolic individuality and influence brain
      development: implications for clinical practice derived from studies on choline
      metabolism.
AB  - One of the underlying mechanisms for metabolic individuality is genetic
      variation. Single nucleotide polymorphisms (SNPs) in genes of metabolic pathways
      can create metabolic inefficiencies that alter the dietary requirement for, and
      responses to, nutrients. These SNPs can be detected using genetic profiling and
      the metabolic inefficiencies they cause can be detected using metabolomic
      profiling. Studies on the human dietary requirement for choline illustrate how
      useful these new approaches can be, as this requirement is influenced by SNPs in
      genes of choline and folate metabolism. In adults, these SNPs determine whether
      people develop fatty liver, liver damage and muscle damage when eating diets low
      in choline. Because choline is very important for fetal development, these SNPs
      may identify women who need to eat more choline during pregnancy. Some of the
      actions of choline are mediated by epigenetic mechanisms that permit 'retuning'
      of metabolic pathways during early life.

PMID- 22614816
TI  - Nutrigenetics and modulation of oxidative stress.
AB  - Oxidative stress develops as a result of an imbalance between the production and
      accumulation of reactive species and the body's ability to manage them using
      exogenous and endogenous antioxidants. Exogenous antioxidants obtained from the
      diet, including vitamin C, vitamin E, and carotenoids, have important roles in
      preventing and reducing oxidative stress. Individual genetic variation affecting
      proteins involved in the uptake, utilization and metabolism of these antioxidants
      may alter their serum levels, exposure to target cells and subsequent
      contribution to the extent of oxidative stress. Endogenous antioxidants include
      the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase,
      paraoxanase, and glutathione S-transferase. These enzymes metabolize reactive
      species and their by-products, reducing oxidative stress. Variation in the genes
      coding these enzymes may impact their enzymatic antioxidant activity and, thus,
      the levels of reactive species, oxidative stress, and risk of disease
      development. Oxidative stress may contribute to the development of chronic
      disease, including osteoporosis, type 2 diabetes, neurodegenerative diseases,
      cardiovascular disease, and cancer. Indeed, polymorphisms in most of the genes
      that code for antioxidant enzymes have been associated with several types of
      cancer, although inconsistent findings between studies have been reported. These
      inconsistencies may, in part, be explained by interactions with the environment,
      such as modification by diet. In this review, we highlight some of the recent
      studies in the field of nutrigenetics, which have examined interactions between
      diet, genetic variation in antioxidant enzymes, and oxidative stress.

PMID- 22614817
TI  - Why are genetics important for nutrition? Lessons from epigenetic research.
AB  - Marked advances were made over the last decade in deciphering the molecular
      mechanisms on how external, nutritional factors can impact on the regulation of
      genes and ultimately their function without modification of the genetic code.
      This field of nutrigenomic research is literally exploding. With the
      understanding of epigenetic control mechanisms, such as DNA methylation, histone
      acetylation, methylation or phosphorylation, as well as the posttranscriptional
      regulation of gene expression via non-coding microRNA, many different
      experimental and analytic approaches were possible to elucidate how varying
      nutritional support might impact on specific functions, with short- and potently
      long-term effects. This review highlights the major principles of epigenetic
      control mechanisms and their link to particular nutritional influences.
      Epidemiological data, such as the Dutch famine studies, suggest that targeted
      nutritional intervention might be causative for long-term effects on health, such
      as the increased risk of cardiovascular diseases and metabolic syndrome in this
      cohort. However, to date most of the knowledge comes from experimental and animal
      data, which cannot be easily transferred to human situations. It is anticipated
      that within the next few years, major advances will be made to translate this
      knowledge of nutritional intervention on gene regulation and expression into
      health preventive programs.

PMID- 22614818
TI  - Ion channels in postnatal neurogenesis: potential targets for brain repair.
AB  - Neural stem and progenitor cells (NSC/NPCs) are unspecialized cells found in the
      adult peri-ventricular and sub-granular zones that are capable of self-renewal,
      migration, and differentiation into new neurons through the remarkable process of
      postnatal neurogenesis. We are now beginning to understand that the concerted
      action of ion channels, multi-pass transmembrane proteins that allow passage of
      ions across otherwise impermeable cellular membranes tightly regulate this
      process. Specific ion channels control proliferation, differentiation and
      survival. Furthermore, they have the potential to be highly selective drug
      targets due to their complex structures. As such, these proteins represent
      intriguing prospects for control and optimization of postnatal neurogenesis for
      neural regeneration following brain injury or disease. Here, we concentrate on
      ion channels identified in adult ventricular zone NSC/NPCs that have been found
      to influence the stages of neurogenesis. Finally, we outline the potential of
      these channels to elicit repair, and highlight the outstanding challenges.

PMID- 22614819
TI  - In situ shaping of Pt nanoparticles directly overgrown on carbon supports.
AB  - Pt cubes immobilized on carbon supports were synthesized by a one pot process in
      the presence of anchoring agents. The anchoring agents provide nucleating sites
      on the support, and also act as shape-controlling agents. In situ shaped cubic
      Pt/C showed superior activity and long-term stability for oxygen reduction
      reaction without an organic removal process.

PMID- 22614821
TI  - Erratum to: Recent developments in the treatment of cachexia: highlights from the
      6th Cachexia Conference.

PMID- 22614820
TI  - T-2 toxin induces apoptosis in differentiated murine embryonic stem cells through
      reactive oxygen species-mediated mitochondrial pathway.
AB  - T-2 toxin, a member of the trichothecene mycotoxin family produced by the
      Fusarium fungi, has been shown to exert a variety of toxic effects on multiple
      targets in vivo. However, the embryonic toxicity of T-2 toxin in vitro remains
      unclear. In the present study, two permanent cell lines, embryonic stem cells (ES
      cells D3) and fibroblast 3T3 cells, were used to evaluate T-2 toxin toxicity.
      Differentiated mouse ES cells were cultivated as embryoid bodies along with T-2
      toxin at different concentrations (0.5, 1, and 2 ng/ml) for 24 h. The increases
      in cellular reactive oxygen species (ROS), lipid and DNA oxidative damage, and
      loss of mitochondrial transmembrane potential were observed at 1 and 2 ng/ml
      concentrations. Flow cytometry showed that T-2 toxin induced cell cycle arrest
      and apoptosis. Furthermore, T-2 toxin opened the mitochondrial permeability
      transition pore, caused the release of cytochrome c from mitochondria and induced
      the upregulation of p53, caspase-9, caspase-3 expression and increased the ratio
      of Bax/Bcl-2. However, T-2 toxin-induced oxidative damage and apoptosis in
      differentiated ES cells decreased significantly in the presence of the
      antioxidant Trolox. Taken together, these results demonstrate that T-2 toxin
      induces oxidative stress and apoptosis in differentiated murine ES cells, and ROS
      mediated mitochondrial pathway plays an important role in T-2 toxin induced
      apoptosis.

PMID- 22614822
TI  - 5-Fluorouracil in combination with cisplatin alters the microRNA expression
      profile in the CNE nasopharyngeal carcinoma cell line.
AB  - Chemotherapy constitutes one of the chief supplementary methods in the treatment
      of nasopharyngeal carcinoma (NPC). 5-Fluorouracil (5-FU) and cisplatin are
      classic chemotherapeutic drugs that have been widely used for NPC treatment.
      Although the aberrant expression of protein-coding genes has been observed after
      chemotherapy, the regulatory mechanisms involved remain poorly understood.
      MicroRNAs (miRNAs) are a newly identified class of small regulatory RNAs involved
      in multiple biological processes and metabolic regulation, including the
      initiation, progression and metastasis of human cancers. In this study, using a
      label-free high-throughput microRNA array technology, the stacking-hybridized
      universal tag (SHUT) assay, we show that 5-FU in combination with cisplatin
      significantly alters the global expression profile of miRNAs in CNE cells. After
      48 h of treatment with a low dose [10% inhibitory concentration (IC10)] of 5-FU
      and/or cisplatin, numerous key miRNAs were shown to be regulated. Compared to the
      431 miRNAs detected in the control cells, 184 miRNAs were significantly expressed
      in the 5-FU-treated cells, while 336 miRNAs were expressed in the cisplatin
      treated cells and 13 miRNAs in the cells treated with the combination of both
      drugs. The majority of these miRNAs are associated with cancer development,
      progression and metastasis. This is the first time that miRNA expression profiles
      in the CNE cell line are shown. Our findings elucidate a potential mechanism
      involved in the chemotherapy of NPC and provide new clues for the treatment of
      NPC.

PMID- 22614823
TI  - IgM-mediated autoimmune responses directed against anchorage epitopes are greater
      in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) than in major
      depression.
AB  - Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and depression are
      considered to be neuro-immune disorders (Maes and Twisk, BMC Medicine 8:35,
      2010). There is also evidence that depression and ME/CFS are accompanied by
      oxidative and nitrosative stress (O&NS) and by increased autoantibodies to a
      number of self-epitopes some of which have become immunogenic due to damage by
      O&NS. The aim of this study is to examine IgM-mediated autoimmune responses to
      different self-epitopes in ME/CFS versus depression. We examined serum IgM
      antibodies to three anchorage molecules (palmitic and myristic acid and S
      farnesyl-L-cysteine); acetylcholine; and conjugated NO-modified adducts in 26
      patients with major depression; 16 patients with ME/CFS, 15 with chronic fatigue;
      and 17 normal controls. Severity of fatigue and physio-somatic (F&S) symptoms was
      measured with the Fibromyalgia and Chronic Fatigue Syndrome Rating Scale. Serum
      IgM antibodies to the three anchorage molecules and NO-phenylalanine were
      significantly higher in ME/CFS than in depression. The autoimmune responses to
      oxidatively, but not nitrosatively, modified self-epitopes were significantly
      higher in ME/CFS than in depression and were associated with F&S symptoms. The
      autoimmune activity directed against conjugated acetylcholine did not differ
      significantly between ME/CFS and depression, but was greater in the patients than
      controls. Partially overlapping pathways, i.e. increased IgM antibodies to a
      multitude of neo-epitopes, underpin both ME/CFS and depression, while greater
      autoimmune responses directed against anchorage molecules and oxidatively
      modified neo-epitopes discriminate patients with ME/CFS from those with
      depression. These autoimmune responses directed against neoantigenic determinants
      may play a role in the dysregulation of key cellular functions in both disorders,
      e.g. intracellular signal transduction, cellular differentiation and apoptosis,
      but their impact may be more important in ME/CFS than in depression.

PMID- 22614824
TI  - Gender and age effects on the continuous reaction times method in volunteers and
      patients with cirrhosis.
AB  - Minimal hepatic encephalopathy (MHE) is a metabolic brain disorder occurring in
      patients with liver cirrhosis. MHE lessens a patient's quality of life, but is
      treatable when identified. The continuous reaction times (CRT) method is used in
      screening for MHE. Gender and age effects on the CRT method are unknown and may
      confound the results. The aim of this study was to standardise the CRT method
      outcomes for age and gender effects. We studied 121 volunteers without known
      disease and 181 patients with cirrhosis by a CRT test. Reaction time to an
      auditory signal was measured 100 times, the 10th, 50th, and 90th reaction time
      percentiles were recorded, and the CRT index was calculated as the 50th
      percentile/(90th percentile-10th percentile), as a measure of intra-individual
      stability in reaction times. In volunteers, men reacted faster than women and
      their reaction times slowed with age. However, neither the gender nor the age
      effect was present regarding the CRT index. The patients with cirrhosis reacted
      slower and with a higher degree of instability than volunteers. Male patients
      reacted faster than female patients, and reaction times tended to slow with age.
      As among the volunteers, there was no gender or age effect on CRT index for the
      patients with cirrhosis. Age and gender influenced reaction times of both
      volunteers and patients with cirrhosis. The CRT index, however, was independent
      of age and gender in both groups. Screening of patients with cirrhosis using the
      CRT index, therefore, identifies brain dysfunction rather than effects of gender
      and age.

PMID- 22614825
TI  - Contact with stimulated T cells up-regulates expression of peptidylarginine
      deiminase 2 and 4 by human monocytes.
AB  - OBJECTIVE: The antigenic targets of the rheumatoid arthritis (RA)-associated
      autoantibodies to "citrullinated" proteins are generated following citrullination
      by a peptidylarginine deiminase (PAD). Of the five PAD isotypes, two - PAD2 and
      PAD4 - are expressed in RA synovial tissue. Within this tissue, the activation of
      macrophages and fibroblasts mediated by T-cell contact or driven by cytokines
      plays a prominent part in the pathogenesis. We wanted to determine whether
      cytokine stimulation and contact with T cells could play a role in PAD expression
      by peripheral blood monocytes and fibroblastic synoviocytes. METHODS: Human
      monocytes and T lymphocytes were derived from the blood of healthy donors. HUT-78
      cells and T lymphocytes were stimulated with PHA and PMA. Human synovial
      fibroblasts were isolated after surgical synoviectomy. The expression of PAD was
      determined by real-time PCR and immunoblot. RESULTS: In monocytes, the PADI2 and
      PADI4 mRNAs were transiently up-regulated by contact with stimulated HUT-78
      and/or T lymphocytes. Positive modulation of the PAD2 and PAD4 proteins were also
      observed upon contact with stimulated HUT-78 T cells. Stimulation by IL-1beta or
      IFN-beta did not modify the PADI2 and PADI4 mRNAs, but enhanced PAD4 protein
      expression. No isotype of PAD was detected at the mRNA or protein level in
      resting or stimulated synovial fibroblasts. CONCLUSION: Contact between
      stimulated T cells and monocyte-macrophages or cytokine-activated monocyte
      macrophages constitutes a highly likely source of PAD2 and PAD4, which are
      observed in inflamed synovial tissues. In contrast, it is most unlikely that
      fibroblastic synoviocytes contribute to PAD expression in rheumatoid synovial
      membranes.

PMID- 22614827
TI  - The role of the 3' untranslated region in post-transcriptional regulation of
      protein expression in mammalian cells.
AB  - The untranslated regions (UTRs) at the 3'end of mRNA transcripts contain
      important sequences that influence the fate of mRNA and thus proteosynthesis. In
      this review, we summarize the information known to date about 3'end processing,
      sequence characteristics including related binding proteins and the role of
      3'UTRs in several selected signaling pathways to delineate their importance in
      the regulatory processes in mammalian cells. In addition to reviewing recent
      advances in the more well known aspects, such as cleavage and polyadenylation
      processes that influence mRNA stability and location, we concentrate on some
      newly emerging concepts of the role of the 3'UTR, including alternative
      polyadenylation sites in relation to proliferation and differentiation and the
      recognition of the multi-functional properties of non-coding RNAs, including
      miRNAs that commonly target the 3'UTR. The emerging picture is of a highly
      complex set of regulatory systems that include autoregulation, cooperativity and
      competition to fine tune proteosynthesis in context-dependent manners.

PMID- 22614826
TI  - Postoperative assessment of free skin flap viability by transcutaneous pO2
      measurement using dynamic phosphorescence imaging.
AB  - BACKGROUND: Free flap transplantation is used more and more frequently in order
      to cover extensive wound defects. The basic prerequisite for successful flap
      salvage after flap failure is a short time interval from failure until revision.
      For this reason many different flap monitoring systems have been tested over the
      last years. But none of them has made the way into clinical routine. OBJECTIVE:
      The aim of this clinical study was to study whether luminescence lifetime imaging
      (LLI) is an adequate method to assess flap viability during the postoperative
      period. In previous experiments LLI was proven to be a precise and non-invasive
      monitoring system for transcutaneous oxygen measurement. METHODS: ptcO2 of 9
      patients was detected during a postoperative period of 72 hours. In all cases the
      transplantation was performed by the same experienced surgeon. During the first 4
      hours almost constant ptcO2 values were detected (53+/-0.7 mmHg). During the
      following time intervals ptcO2 values decreased and reached a more or less
      constant level after approximately 12 hours. The mean ptcO2 decreased from 53+/
      0.7 mmHg to 39+/-1.0 mmHg. In one case an immediate decrease of ptcO2 below 10
      mmHg was observed and a subsequently intervention was necessary to improve flap
      perfusion. CONCLUSION: In this clinical trial, perfusion dynamics after free flap
      transplantation as well as the detection of vascular complications were
      demonstrated using LLI. Based on these data, LLI seems to be a sensitive and
      adequate monitoring system for the evaluation of free flap viability.

PMID- 22614828
TI  - Conservation and regulation of alternative splicing by dynamic inter- and intra
      intron base pairings in Lepidoptera 14-3-3xi pre-mRNAs.
AB  - Alternative splicing of pre-mRNAs greatly contributes to diversity in products
      generated from a single gene. However, the underlying regulatory mechanisms are
      poorly understood. In the present study, we describe evolutionarily conserved
      intra-intronic and inter-intronic RNA secondary structures. Mutation experiments
      revealed that intra-intronic RNA secondary structure causes steric hindrance to
      enforce mutual splicing exclusivity, while inter-intronic RNA pairing largely
      functions through a looped-out mechanism. Moreover, mutually exclusive splicing
      may be regulated by RNA pairing competition between intra- and inter-introns.
      Importantly, the resulting dynamic RNA architecture largely controls mutually
      exclusive splicing, although cis-acting regulatory sequences may fine-tune this
      process. Our results emphasize the importance of dynamic RNA architecture in
      alternative splicing.

PMID- 22614830
TI  - The bacterial CRISPR/Cas system as analog of the mammalian adaptive immune
      system.
AB  - Bacteria, like mammals, have to constantly defend themselves from viral attack.
      Like mammals, they use both innate and adaptive defense mechanisms. In this point
      of view we highlight the commonalities between defense systems of bacteria and
      mammals. Our focus is on the recently discovered bacterial adaptive immune
      system, the clustered regularly interspaced short palindromic repeats (CRISPR)
      and their associated proteins (Cas). We suggest that fundamental aspects of
      CRISPR/Cas immunity may be viewed in light of the vast accumulated knowledge on
      the mammalian immune system, and propose that further insights will be revealed
      by thorough comparison between the systems.

PMID- 22614829
TI  - New kid on the ID block: neural functions of the Nab2/ZC3H14 class of Cys3His
      tandem zinc-finger polyadenosine RNA binding proteins.
AB  - Polyadenosine RNA binding proteins (Pabs) play critical roles in regulating the
      polyadenylation, nuclear export, stability, and translation of cellular RNAs.
      Although most Pabs are ubiquitously expressed and are thought to play general
      roles in post-transcriptional regulation, mutations in genes encoding these
      factors have been linked to tissue-specific diseases including muscular dystrophy
      and now intellectual disability (ID). Our recent work defined this connection to
      ID, as we showed that mutations in the gene encoding the ubiquitously expressed
      Cys3His tandem zinc-finger (ZnF) Pab, ZC3H14 (Zinc finger protein, CCCH-type,
      number 14) are associated with non-syndromic autosomal recessive intellectual
      disability (NS-ARID). This study provided a first link between defects in Pab
      function and a brain disorder, suggesting that ZC3H14 plays a required role in
      regulating RNAs in nervous system cells. Here we highlight key questions raised
      by our study of ZC3H14 and its ortholog in the fruit fly Drosophila melanogaster,
      dNab2, and comment on future approaches that could provide insights into the
      cellular and molecular roles of this class of zinc finger-containing Pabs. We
      propose a summary model depicting how ZC3H14-type Pabs might play particularly
      important roles in neuronal RNA metabolism.

PMID- 22614831
TI  - The differential expression of glutathione peroxidase 1 and 4 depends on the
      nature of the SECIS element.
AB  - Selenocysteine insertion into selenoproteins involves the translational recoding
      of UGA stop codons. In mammals, selenoprotein expression further depends on
      selenium availability, which has been particularly described for glutathione
      peroxidase 1 and 4 (Gpx1 and Gpx4). The SECIS element located in the 3'UTR of the
      selenoprotein mRNAs is a modulator of UGA recoding efficiency in adequate
      selenium conditions. One of the current models for the UGA recoding mechanism
      proposes that the SECIS binds SECIS-binding protein 2 (SBP2), which then recruits
      a selenocysteine-specific elongation factor (EFsec) and tRNA (Sec)  to the
      ribosome, where L30 acts as an anchor. The involvement of the SECIS in modulation
      of UGA recoding activity was investigated, together with SBP2 and EFsec, in
      Hek293 cells cultured with various selenium levels. Luciferase reporter
      constructs, in transiently or stably expressing cell lines, were used to analyze
      the differential expression of Gpx1 and Gpx4. We showed that, upon selenium
      fluctuation, the modulation of UGA recoding efficiency depends on the nature of
      the SECIS, with Gpx1 being more sensitive than Gpx4. Attenuation of SBP2 and
      EFsec levels by shRNAs confirmed that both factors are essential for efficient
      selenocysteine insertion. Strikingly, in a context of either EFsec or SBP2
      attenuation, the decrease in UGA recoding efficiency is dependent on the nature
      of the SECIS, GPx1 being more sensitive. Finally, the profusion of selenium of
      the culture medium exacerbates the lack of factors involved in selenocysteine
      insertion.

PMID- 22614832
TI  - The SID-1 double-stranded RNA transporter is not required for systemic RNAi in
      the migratory locust.
AB  - Systemic RNAi, the spreading of RNAi effects to cells and tissues that have not
      initially encountered a dsRNA trigger, is a common phenomenon in many organisms.
      However, the underlying mechanisms of systemic RNAi remain largely unknown. Here,
      we studied the characteristics and possible mechanisms of systemic RNAi in
      Locusta migratoria. We observed that the locust has pronounced sensitive systemic
      RNAi in response to dsRNA injection for both broadly-expressed as well as tissue
      specific genes. Only a 30 pg (dsRNA / mg tissues) dose could induce significant
      systemic RNAi effects. Only one SID-1 ortholog (LmSID-1) was identified in the
      locust genome, which exhibited a progressively increasing expression pattern with
      development and its expression was enriched in the gonad. To test the role of
      LmSID-1 in systemic RNAi, we performed in vitro and in vivo experiments. The
      results from in vivo experiments showed that silencing of LmSID-1 gene dose not
      influence RNAi effects of other genes. The results from in vitro experiments
      confirmed that the expression of the LmSID-1 protein in Drosophila S2 cells could
      not enhance dsRNA uptake. Thus, these findings imply the existence of alternative
      mechanisms underlying insect systemic RNAi, which may be different from
      Caenorhabditis elegans or mammals.

PMID- 22614833
TI  - Long-distance movement of Arabidopsis FLOWERING LOCUS T RNA participates in
      systemic floral regulation.
AB  - The finding of mRNA acting as a systemic information molecule is one of the most
      exciting discoveries in recent plant biology. However, evidence demonstrating the
      functional significance of non-cell autonomous RNA remains limited. Recent
      analyses of Arabidopsis and rice revealed FLOWERING LOCUS T (FT) protein as a
      systemic florigenic signal. However, whether the FT RNA also participates in
      systemic floral regulation remains controversial. By using Arabidopsis cleft
      grafting experiments, we showed that the RNA of Arabidopsis FT undergoes long
      distance movement from the stock to the scion apex in both FT transformants and
      non-transformants. In addition, the sequences of FT RNA are sufficient to target
      a cell-autonomous RNA for long-distance movement. Therefore, FT RNA is a bona
      fide non-cell autonomous RNA. To examine the systemic action of FT RNA, we
      uncoupled the movement of FT RNA from protein by fusing FT with RED FLUORESCENT
      PROTEIN (RFP). When RFP-FT protein was retained in companion cells, the detection
      of RFP-FT RNA correlates with floral promotion in the scion. Further depletion of
      the translocated RFP-FT RNA by RNAi or artificial miRNA against FT delayed the
      floral promotion, indicating that the translocated FT RNA acts as a part of the
      systemic floral signaling. Our results indicate that both FT RNA and protein move
      long distance and act redundantly to integrate the photoperiodic signals.

PMID- 22614834
TI  - The role of decapping proteins in the miRNA accumulation in Arabidopsis thaliana.
AB  - Decapping 1 (DCP1), Decapping 2 (DCP2) and VARICOSE (VCS) are components of the
      decapping complex that removes the 7-methyl-guanosine 5'-diphosphate from the 5'
      end of mRNAs. In animals, the decapping proteins are involved in miRNA-mediated
      gene silencing, whereas in plants the roles of the decapping proteins in the
      miRNA pathway are not well understood. Here we demonstrated that the accumulation
      of miRNAs decreased in dcp1, dcp2 and vcs mutants, indicating that DCP1, DCP2 and
      VCS are important for the miRNA pathway in Arabidopsis thaliana. The primary
      miRNAs (pri-miRNAs) did not increase and miRNA biogenesis components did not
      decrease in these mutants, suggesting that the miRNA decrease in decapping
      mutants is not due to the defect of pri-miRNA processing. We showed that the
      accumulation of miRNA targets increased concomitantly with the decrease of miRNA
      in the decapping mutants. Our results suggested that the seedling lethal
      phenotypes in the dcp1, dcp2 and vcs mutants are caused not only by the defect in
      decapping, but also by the disruption of miRNA-mediated gene regulation.

PMID- 22614835
TI  - An enzyme-coupled high-throughput assay for screening RNA methyltransferase
      activity in E. coli cell lysate.
AB  - Post-transcriptional modifications of RNA diversify the genetically encoded
      sequences and play important roles in fundamental cellular processes like mRNA
      and rRNA maturation. Most RNA methylations are catalyzed by S-adenosylmethionine
      dependent RNA methyltransferases. An assay for rapid and easy detection of this
      enzymatic activity would be highly desirable to identify novel RNA
      methyltransferases, test S-adenosylmethionine analogs or screen RNA
      methyltransferase inhibitors. We have developed an enzyme-coupled assay to
      determine the activity of trimethylguanosine synthases, a class of RNA
      methyltransferases responsible for RNA cap hypermethylation in eukaryotes. We
      show that this assay can be used in E. coli cell lysate to measure the activity
      of recombinantly produced trimethylguanosine synthase. Potential hits are
      validated for formation of hypermethylated product using HPLC and MALDI-TOF-MS.
      Furthermore, we demonstrate how this assay can be implemented to screen
      methyltransferase inhibitors.

PMID- 22614836
TI  - Drosophila Pur-alpha binds to trinucleotide-repeat containing cellular RNAs and
      translocates to the early oocyte.
AB  - Pur-alpha was identified as a DNA-binding protein with high affinity for the
      single-stranded PUR-motif (GGN)n. Bound to DNA, Pur-alpha can both activate and
      repress transcription. In addition, Pur-alpha binds to RNA and may participate in
      nuclear RNA export as well as transport of cytoplasmic neuronal mRNP granules.
      The heritable trinucleotide-repeat expansion disease Fragile X associated Tremor
      and Ataxia Syndrome (FXTAS) leads to interaction of Pur-alpha with mutant,
      abnormally long r(CGG)n stretches, which appears to titrate the protein away from
      its physiologic mRNA targets into nuclear RNA-protein aggregates. We examined the
      function of Drosophila Pur-alpha and demonstrate that the protein accumulates in
      the growing oocyte early in oogenesis. Co-purifying proteins reveal that Pur
      alpha is part of transported mRNP complexes, analogous to its reported role in
      nerve cells. We analyzed the subcellular localization of mutant GFP-Pur-alpha
      fusion proteins where either nucleic acid binding or dimerization, or both, were
      prevented. We propose that association with mRNAs occurs in the nucleus and is
      required for nuclear export of the complex. Furthermore, efficient translocation
      into the oocyte also requires RNA binding as well as dimerization. RNA binding
      assays demonstrate that recombinant Drosophila Pur-alpha can bind r(CGG) 4 with
      higher affinity than previously thought. Related sequences, such as r(CAG) 4 and
      the consensus sequence of the opa-repeat r(CAG) 3CAA, can also associate with Pur
      alpha in vitro and in vivo. The mRNA target spectrum of Pur-alpha may therefore
      be larger than previously anticipated.

PMID- 22614837
TI  - Z' factor including siRNA design quality parameter in RNAi screening experiments.
AB  - RNA interference (RNAi) high-content screening (HCS) enables massive parallel
      gene silencing and is increasingly being used to reveal novel connections between
      genes and disease-relevant phenotypes. The application of genome-scale RNAi
      relies on the development of high quality HCS assays. The Z' factor statistic
      provides a way to evaluate whether or not screening run conditions (reagents,
      protocols, instrumentation, kinetics, and other conditions not directly related
      to the test compounds) are optimized. Z' factor, introduced by Zhang et al., ( 1)
      is a dimensionless value that represents both the variability and the dynamic
      range between two sets of sample control data. This paper describe a new
      extension of the Z' factor, which integrates bioinformatics RNAi non-target
      compounds for screening quality assessment. Currently presented Z' factor is
      based on positive and negative control, which may not be sufficient for RNAi
      experiments including oligonucleotides (oligo) with lack of knock-down. This
      paper proposes an algorithm which extends existing algorithm by using additional
      controls generetaed from on-target analysis.

PMID- 22614838
TI  - Multiple insert size paired-end sequencing for deconvolution of complex
      transcriptomes.
AB  - Deep sequencing of transcriptomes allows quantitative and qualitative analysis of
      many RNA species in a sample, with parallel comparison of expression levels,
      splicing variants, natural antisense transcripts, RNA editing and transcriptional
      start and stop sites the ideal goal. By computational modeling, we show how
      libraries of multiple insert sizes combined with strand-specific, paired-end (SS
      PE) sequencing can increase the information gained on alternative splicing,
      especially in higher eukaryotes. Despite the benefits of gaining SS-PE data with
      paired ends of varying distance, the standard Illumina protocol allows only non
      strand-specific, paired-end sequencing with a single insert size. Here, we modify
      the Illumina RNA ligation protocol to allow SS-PE sequencing by using a custom
      pre-adenylated 3' adaptor. We generate parallel libraries with differing insert
      sizes to aid deconvolution of alternative splicing events and to characterize the
      extent and distribution of natural antisense transcription in C. elegans. Despite
      stringent requirements for detection of alternative splicing, our data increases
      the number of intron retention and exon skipping events annotated in the Wormbase
      genome annotations by 127% and 121%, respectively. We show that parallel
      libraries with a range of insert sizes increase transcriptomic information gained
      by sequencing and that by current established benchmarks our protocol gives
      competitive results with respect to library quality.

PMID- 22614839
TI  - PRMT1 is required for RAP55 to localize to processing bodies.
AB  - In eukaryotic cells, components of messenger ribonucleoproteins (mRNPs) are often
      detected in cytoplasmic granules, such as processing bodies (P-bodies) and stress
      granules (SGs) where translationally repressed mRNAs accumulate. RAP55A, which is
      an RNA binding component of mRNPs, acts as a translational repressor and
      localizes to P-bodies and SGs. We found here that a homologous protein RAP55B
      also localized to P-bodies when expressed in human cultured cells. When RAP55A or
      RAP55B was highly expressed in the cells, they induced the formation of SG-like
      large cytoplasmic mRNP granules that contained both P-body and SG components,
      indicating that RAP55 is important for the assembly of cytoplasmic mRNP granules.
      In addition, we found that RAP55A associated with protein arginine
      methyltransferases PRMT1 and PRMT5. Multiple arginine residues of RAP55A were
      indeed asymmetrically dimethylated in the cell and PRMT1 was shown to be a
      component of large mRNP granules induced by RAP55A overexpression. Although PRMT1
      did not accumulate in P-bodies, siRNA-mediated knockdown of PRMT1 impaired the
      localization of RAP55A to P-bodies, while other components were still retained in
      these structures. Thus, our data indicate that RAP55 is important for the
      assembly of cytoplasmic mRNP granules and that PRMT1 is required for RAP55A to
      localize to P-bodies.

PMID- 22614840
TI  - Breast cancer proteomics reveals a positive correlation between glyoxalase 1
      expression and high tumor grade.
AB  - Breast cancer is the neoplasia with the highest incidence in women worldwide.
      Proteomics approaches have accelerated the discovery of diagnostic and prognostic
      biomarkers. Here, we compared the proteomic profiles of breast tumors versus non
      tumoral tissues in order to identify modulated proteins, which could represent
      potential markers associated to clinical features. By two-dimensional
      electrophoresis, we detected 28 differentially expressed proteins. Among these,
      21 proteins were up-regulated and 7 were down-regulated in tumors (p<0.05).
      Proteins were identified using LC/ESI-MS/MS tandem mass spectrometry. One protein
      was identified as glyoxalase 1 (GLO1), an enzyme involved in detoxification of
      methylglyoxal, a cytotoxic product of glycolysis. GLO1 overexpression was
      confirmed by western blot assays in paired normal and tumor breast tissues in
      clinical stages I-III, and by immunohistochemistry on tissue microarrays (TMA)
      comprising a cohort of 98 breast tumors and 20 healthy specimens. Results from
      TMA demonstrated that GLO1 is overexpressed in 79% of tumors. Interestingly, GLO1
      up-regulation correlates with advanced tumor grade (p<0.05). These findings
      demonstrate the association of GLO1 overexpression with tumor grade and pointed
      out for additional studies to establish the importance of GLO1 in breast cancer.

PMID- 22614841
TI  - Predictive value and clinical interest of the antiphospholipid score: comment on
      the article by Otomo et al.

PMID- 22614842
TI  - Simultaneous growth of self-patterned carbon nanotube forests with dual height
      scales.
AB  - In this study, we report on a unique, one-step fabrication technique enabling the
      simultaneous synthesis of vertically aligned multi-walled carbon nanotubes (VA
      MWCNTs) with dual height scales through alcohol catalyzed chemical vapor
      deposition (ACCVD). Regions of VA-MWCNTs with different heights were well
      separated from each other leading to a self-patterning on the surface. We devised
      a unique layer-by-layer process for application of catalyst and inhibitor
      precursors on oxidized Si (100) surfaces before the ACCVD step to achieve a
      hierarchical arrangement. Patterning could be controlled by adjusting the
      molarity and application sequence of precursors. Contact angle measurements on
      these self-patterned surfaces indicated that manipulation of these hierarchical
      arrays resulted in a wide range of hydrophobic behavior changing from that of a
      sticky rose petal to a lotus leaf.

PMID- 22614843
TI  - Letter to the Editor.

PMID- 22614844
TI  - Horizontal and vertical ridge augmentation in localized alveolar deficient sites:
      a retrospective case series.
AB  - PURPOSE: This study reviews the clinical outcomes of ridge augmentations
      performed via horizontal- or vertical-guided bone regeneration (h-GBR, v-GBR) or
      edentulous ridge expansion. MATERIALS AND METHODS: The degree of defect
      correction, the marginal bone level, and the horizontal stability of the
      augmented bone (five patients) were examined with a new proposed rigid resin
      survey template. RESULTS: Thirty ridge defects ranging from 1 to 8 mm were
      corrected, and 56 implants were positioned. The percentages of alveolar defect
      correction were 91.85% +/- 22.30%, 97.13% +/- 4.48%, and 90.42% +/- 11.93% for h
      GBR, edentulous ridge expansion, and v-GBR, respectively; a limited amount of
      marginal bone level was reported for all three groups, while a large amount of
      horizontal bone resorption was detected. CONCLUSIONS: All surgical techniques
      considered in this study are predictable procedures, and the proposed survey
      template measurement system showed to be a reliable method of evaluating
      horizontal bone stability of the augmented ridges.

PMID- 22614845
TI  - Strain gauge analysis of the effect of porcelain firing simulation on the
      prosthetic misfit of implant-supported frameworks.
AB  - OBJECTIVES: This study investigated the effect of porcelain firing on the misfit
      of implant-supported frameworks and analyzed the influence of preheat treatment
      on the dimensional alterations. MATERIALS AND METHODS: Four external-hex
      cylindrical implants were placed in polyurethane block. Ten frameworks of screw
      retained implant-supported prostheses were cast in Pd-Ag using 2 procedures: (1)
      control group (CG, n = 5): cast in segments and laser welded; and test group (TG,
      n = 5): cast in segments, preheated, and laser welded. All samples were subjected
      to firing to simulate porcelain veneering firing. Strain gauges were bonded
      around the implants, and microstrain values (MUepsilon = 10-6epsilon) were
      recorded after welding (M1), oxidation cycle (M2), and glaze firing (M3). Data
      were statistically analyzed (2-way analysis of variance, Bonferroni, alpha =
      0.05). RESULTS: The microstrain value in the CG at M3 (475.2 MUepsilon) was
      significantly different from the values observed at M1 (355.6 MUepsilon) and M2
      (413.9 MUepsilon). The values at M2 and M3 in the CG were not statistically
      different. Microstrain values recorded at different moments (M1: 361.6
      MUepsilon/M2: 335.3 MUepsilon/M3: 307.2 MUepsilon) did not show significant
      difference. CONCLUSIONS: The framework misfit deteriorates during firing cycles
      of porcelain veneering. Metal distortion after porcelain veneering could be
      controlled by preheat treatment.

PMID- 22614846
TI  - Alveolar bone regeneration by implantation of nacre and B-tricalcium phosphate in
      guinea pig.
AB  - PURPOSE: To investigate alveolar bone regeneration after nacre implantation in
      comparison to beta-tricalcium phosphate (beta-TCP) for the potential application
      to bone grafting. MATERIAL AND METHODS: The rod-shaped, 2 * 2 mm in diameter and
      length, implanted materials were prepared from nacre particles of the giant
      oyster (Pinctada maxima), and beta-TCP (Chronos; Synthes, Switzerland) particles.
      Bilateral drilling procedures were performed in 10 male guinea pigs in the
      mandible. Eight animals were implanted with nacre and beta-TCP rods on each side
      of the mandibles. Two animals were sham operated. The animals were sacrificed
      after 30 and 60 days during the healing period. Decalcified histological sections
      of the mandibles were stained with azan stain. RESULTS: Alveolar bone
      regeneration in surgically created defects was more effective in material
      implanted groups than in the sham-operated group. The nacre-implanted group
      exhibited the highest new bone formation, followed by the beta-TCP-implanted
      group and the sham-operated group, respectively. Large space filling with some
      fibrous tissue in central region of the defected site in beta-TCP-implanted and
      sham-operated mandibles was noted. CONCLUSION: The results demonstrate the
      feasibility of using nacre as an alternative bone graft material.

PMID- 22614847
TI  - Surgical workflow management schemata for cataract procedures. process model
      based design and validation of workflow schemata.
AB  - OBJECTIVE: Workflow guidance of surgical activities is a challenging task.
      Because of variations in patient properties and applied surgical techniques,
      surgical processes have a high variability. The objective of this study was the
      design and implementation of a surgical workflow management system (SWFMS) that
      can provide a robust guidance for surgical activities. We investigated how many
      surgical process models are needed to develop a SWFMS that can guide cataract
      surgeries robustly. METHODS: We used 100 cases of cataract surgeries and acquired
      patient-individual surgical process models (iSPMs) from them. Of these,
      randomized subsets iSPMs were selected as learning sets to create a generic
      surgical process model (gSPM). These gSPMs were mapped onto workflow nets as
      workflow schemata to define the behavior of the SWFMS. Finally, 10 iSPMs from the
      disjoint set were simulated to validate the workflow schema for the surgical
      processes. The measurement was the successful guidance of an iSPM. RESULTS: We
      demonstrated that a SWFMS with a workflow schema that was generated from a subset
      of 10 iSPMs is sufficient to guide approximately 65% of all surgical processes in
      the total set, and that a subset of 50 iSPMs is sufficient to guide approx. 80%
      of all processes. CONCLUSION: We designed a SWFMS that is able to guide surgical
      activities on a detailed level. The study demonstrated that the high inter
      patient variability of surgical processes can be considered by our approach.

PMID- 22614851
TI  - Neuro-oncology: Nanoparticle imaging could guide brain tumour surgery.

PMID- 22614848
TI  - Neuromuscular disease: IVIg for neuromuscular disease-effective but expensive.

PMID- 22614852
TI  - Stroke: initial stroke volume is an independent outcome predictor.

PMID- 22614854
TI  - Stroke: is spot sign the answer for intracerebral haemorrhage?

PMID- 22614856
TI  - Stroke: B vitamins show benefit in absence of antiplatelet therapy.

PMID- 22614857
TI  - Chemical composition of Artemisia annua L. leaves and antioxidant potential of
      extracts as a function of extraction solvents.
AB  - This study was conducted to investigate the chemical and nutritional composition
      of Artemisia annua leaves in addition to determination of antioxidant potential
      of their extracts prepared in different solvents. Chemical composition was
      determined by quantifying fat, protein, carbohydrate, fiber, tocopherol, phytate,
      and tannin contents. Extraction of A. annua leaves, for antioxidant potential
      evaluation, was carried out using five solvents of different polarities, i.e.,
      hexane, chloroform, ethyl acetate, methanol and water. Antioxidant potential was
      evaluated by estimating total phenolic (TPC), flavonoid (TFC) contents, ferric
      reducing antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC),
      DPPH radical scavenging activity and lipid peroxidation. Efficiency of different
      solvents was compared for the yield of antioxidant extracts from leaf samples and
      a clear variation was observed. The highest TPC, TFC, TEAC, DPPH radical
      scavenging and lowest lipid peroxidation were observed in MeOH extracts, whereas
      aqueous extract exhibited high ferric reducing antioxidant power; suggesting MeOH
      to be the most favorable extractant.

PMID- 22614858
TI  - Protective effect of T. violacea rhizome extract against hypercholesterolemia
      induced oxidative stress in Wistar rats.
AB  - The present study examines the effect of methanolic extract of T. violacea
      rhizomes on high cholesterol (2%) diet fed rats (HCD). At the end of 4 weeks,
      serum total protein, albumin, reduced glutathione (GSH), and markers of oxidative
      stress viz., catalase (CAT), superoxide dismutase (SOD), thiobarbituric acid
      reactive substances (TBARS--a marker of lipid peroxidation), glutathione-S
      transferase (GST) and glutathione peroxidase (GPx) in the serum, aorta, liver and
      heart of HCD and normal rats were assessed and compared. A significant (p < 0.05)
      elevation in TBARS, and a reduction (p < 0.05) in serum total protein, albumin,
      GSH and antioxidant enzyme activities was observed in tissues of HCD fed rats
      compared with the normal group. Co-administration of crude extracts of T.
      violacea rhizomes protected the liver, heart, serum and aorta against HCD-induced
      lipid peroxidation in a dose dependant manner. The activities of the extract (500
      mg/kg) compared favorably with gemfibrozil. The extracts also protected against
      HCD-induced reduction in serum total protein, GSH and restored the activities of
      antioxidant tissues (liver, heart and aorta) enzymes to near normal values. This
      result suggested that consumption of T. violacea rhizome may help to protect
      against hypercholesterolemia- induced oxidative stress diseases in the heart and
      liver.

PMID- 22614859
TI  - Effect of soluble sulfide on the activity of luminescent bacteria.
AB  - Sulfide is an important water pollutant widely found in industrial waste water
      that has attracted much attention. S2-, as a weak acidic anion, is easy
      hydrolyzed to HS- and H2S in aqueous solution. In this study, biological tests
      were performed to establish the toxicity of sulfide solutions on luminescent
      bacteria. Considering the sulfide solution was contained three substances--S2-,
      HS- and H2S--the toxicity test was performed at different pH values to
      investigate which form of sulfide increased light emission and which reduced
      light emission. It was shown that the EC50 values were close at pH 7.4, 8.0 and
      9.0 which were higher than pH 5 and 10. The light emission and sulfide
      concentrations displayed an inverse exponential dose-response relationship within
      a certain concentration range at pH 5, 6.5 and 10. The same phenomenon occurred
      for the high concentration of sulfide at pH 7.4, 8 and 9, in which the
      concentration of sulfide was HS- >> H2S > S2-. An opposite hormesis-effect
      appeared at the low concentrations of sulfide.

PMID- 22614860
TI  - Physicochemical characterization and cytotoxic activity evaluation of
      hydroxymethylferrocene:beta-cyclodextrin inclusion complex.
AB  - An inclusion complex of hydroxymethylferrocene (FeMeOH) with beta-cyclodextrin
      (beta-CD) was prepared in the solid state by different techniques such as
      physical mixture, coprecipitation, kneading and freeze-drying. The formation of
      the inclusion complex was confirmed by X-ray Powder Diffractometry and Fourier
      Transform-Infrared spectroscopy. In aqueous solution, the 1:1 stoichiometry was
      established by a Job plot. The inclusion complex formation was also investigated
      by NMR and the stability constant (Kb) of the complex was determined to be 478 M
      1, which is in agreement with that obtained with UV-Vis tritation (Kb = 541.3 M
      1). The phase solubility study showed a diagram classified as Bs type and that
      the solubility of FeMeOH was slightly increased in the presence of beta-CD.
      Furthermore, utilizing phase solubility diagram data, the Kb was estimated to be
      equal to 528.0 M-1. The cytotoxic activity of FeMeOH and its complexation product
      with beta-CD was determined using the MTT-assay on MDA-MB-231 cell line, showing
      that the inclusion complex has a higher capability of inhibiting cell growth
      compared to that of pure FeMeOH.

PMID- 22614861
TI  - Antioxidant, antimicrobial and tyrosinase inhibitory activities of xanthones
      isolated from Artocarpus obtusus F.M. Jarrett.
AB  - One of the most promising plants in biological screening test results of thirteen
      Artocarpus species was Artocarpus obtusus FM Jarrett and detailed phytochemical
      investigation of powdered dried bark of the plant has led to the isolation and
      identification of three xanthones; pyranocycloartobiloxanthone A (1),
      dihydroartoindonesianin C (2) and pyranocycloartobiloxanthone B (3). These
      compounds were screened for antioxidant, antimicrobial and tyrosinase inhibitory
      activities. Pyranocycloartobiloxanthone A (1) exhibited a strong free radical
      scavenger towards DPPH free radicals with IC50 value of 2 ug/mL with prominent
      discoloration observed in comparison with standard ascorbic acid, alpha
      tocopherol and quercetin, The compound also exhibited antibacterial activity
      against methicillin resistant Staphylococcus aureus (ATCC3359) and Bacillus
      subtilis (clinically isolated) with inhibition zone of 20 and 12 mm,
      respectively. However the other two xanthones were found to be inactive. For the
      tyrosinase inhibitory activity, again compound (1) displayed strong activity
      comparable with the standard kojic acid.

PMID- 22614862
TI  - Synthesis and bioactivity of secondary metabolites from marine sponges containing
      dibrominated indolic systems.
AB  - Marine sponges. (e.g., Hyrtios sp., Dragmacidin sp., Aglophenia pleuma, Aplidium
      cyaneum, Aplidium meridianum.) produce bioactive secondary metabolites involved
      in their defence mechanisms. Recently it was demonstrated that several of those
      compounds show a large variety of biological activities against different human
      diseases with possible applications in medicinal chemistry and in pharmaceutical
      fields, especially related to the new drug development process. Researchers have
      focused their attention principally on secondary metabolites with anti-cancer and
      cytotoxic activities. A common target for these molecules is the cytoskeleton,
      which has a central role in cellular proliferation, motility, and profusion
      involved in the metastatic process associate with tumors. In particular, many
      substances containing brominated indolic rings such as 5,6-dibromotryptamine, 5,6
      dibromo-N-methyltryptamine, 5,6-dibromo-N-methyltryptophan (dibromoabrine), 5,6
      dibromo-N,N-dimethyltryptamine and 5,6-dibromo-L-hypaphorine isolated from
      different marine sources, have shown anti-cancer activity, as well as antibiotic
      and anti-inflammatory properties. Considering the structural correlation between
      endogenous monoamine serotonin with marine indolic alkaloids 5,6-dibromoabrine
      and 5,6-dibromotryptamine, a potential use of some dibrominated indolic
      metabolites in the treatment of depression-related pathologies has also been
      hypothesized. Due to the potential applications in the treatment of various
      diseases and the increasing demand of these compounds for biological assays and
      the difficult of their isolation from marine sources, we report in this review a
      series of recent syntheses of marine dibrominated indole-containing products.

PMID- 22614863
TI  - Synthesis and evaluation of new beta-carboline-3-(4-benzylidene)-4H-oxazol-5-one
      derivatives as antitumor agents.
AB  - In the present work, we report the synthesis and in vitro anticancer and
      antimicrobial activity evaluation of a new series of 1-substituted-beta-carboline
      derivatives bearing a 4-benzylidene-4H-oxazol-5-one unity at C-3. The compound 2
      [1-(4-methoxyphenyl)-9H-beta-carbolin-3-yl]-4-(benzylidene)-4H-oxazol-5-one (11)
      was the most active derivative, exhibiting a potent cytotoxic activity against
      glioma (U251), prostate (PC-3) and ovarian (OVCAR-03) cancer cell lines with IC50
      values of 0.48, 1.50 and 1.07 uM, respectively. An in silico study of the ADME
      properties of the novel synthesized beta-carboline derivatives was also
      performed.

PMID- 22614864
TI  - Preussianone, a new flavanone-chromone biflavonoid from Garcinia preussii Engl.
AB  - A new flavanone-chromone biflavonoid, preussianone (1), has been isolated from
      the leaves of Garcinia preussii, along with four known biflavonoids. The absolute
      stereostructures were elucidated by chemical, spectroscopic, and chiroptical
      methods. The biological properties of the new biflavonoid against several
      bacterial strains were evaluated.

PMID- 22614865
TI  - A QSAR study of environmental estrogens based on a novel variable selection
      method.
AB  - A large number of descriptors were employed to characterize the molecular
      structure of 53 natural, synthetic, and environmental chemicals which are
      suspected of disrupting endocrine functions by mimicking or antagonizing natural
      hormones and may thus pose a serious threat to the health of humans and wildlife.
      In this work, a robust quantitative structure-activity relationship (QSAR) model
      with a novel variable selection method has been proposed for the effective
      estrogens. The variable selection method is based on variable interaction (VSMVI)
      with leave-multiple-out cross validation (LMOCV) to select the best subset.
      During variable selection, model construction and assessment, the Organization
      for Economic Co-operation and Development (OECD) principles for regulation of
      QSAR acceptability were fully considered, such as using an unambiguous multiple
      linear regression (MLR) algorithm to build the model, using several validation
      methods to assessment the performance of the model, giving the define of
      applicability domain and analyzing the outliers with the results of molecular
      docking. The performance of the QSAR model indicates that the VSMVI is an
      effective, feasible and practical tool for rapid screening of the best subset
      from large molecular descriptors.

PMID- 22614866
TI  - High levels of methylmercury in guano and ornithogenic coral sand sediments on
      Xisha islands, South China sea.
AB  - This study determined the distribution and main source of methylmercury in
      ornithogenic coral sand sediments and pure guano collected from Guangjin and
      Jinqing islets of the South China Sea. Results showed that the levels of
      methylmercury (MeHg) and total mercury (THg), as well as the percentage of MeHg
      relative to THg (%MeHg), are high in both fresh and ancient guano samples. %MeHg
      in ancient guano exceeded 70 %, much greater than that in fresh seabird droppings
      (~45 %). These results suggest that excretion through feces likely plays an
      important role in the cycling of MeHg by seabirds. Guano has been identified as
      the major source of MeHg in the ornithogenic coral sand sediments in the Xisha
      Islands. The close relationship between MeHg and guano-derived phosphorus has
      weakened considerably since 1840 AD. This is probably caused by a significant
      increase in THg and MeHg in modern guano samples due to the recent increase of Hg
      pollution. %MeHg in the ornithogenic coral sand sediments is extremely high,
      ranging from 10 to 30 % (average 20 %).

PMID- 22614867
TI  - Nano-TiO2-induced apoptosis by oxidative stress-mediated DNA damage and
      activation of p53 in human embryonic kidney cells.
AB  - The aim of the present study is to explore the mechanism of cytotoxic and
      genotoxic effects of TiO(2) nanoparticles on human embryonic kidney (HEK-293)
      cells. Toxicity was evaluated using changes in various cellular parameters of HEK
      293 cells like morphology, viability, metabolic activity, oxidative stress and
      apoptosis. Oxidative stress was measured by the level of reactive oxygen species
      (ROS), lipid peroxidation, superoxide dismutase, catalase and glutathione
      peroxidase. Apoptosis induced by nano-TiO(2) was characterized by PI staining and
      DNA ladder assay. Furthermore, apoptotic proteins such as p53 and Bax were
      analysed by western blot. Our results indicate that nano-TiO(2) induces
      cytotoxicity in a time- and dose-dependent manner. Oxidative stress and apoptosis
      were induced by exposure to nano-TiO(2). Moreover, the expression of p53, Bax and
      caspase-3 were increased in a dose-dependent pattern. In conclusion, ROS-mediated
      oxidative stress, the activation of p53, Bax, caspase-3 and oxidative DNA damage
      are involved in the mechanistic pathways of nano-TiO(2)-induced apoptosis in HEK
      293 cells.

PMID- 22614868
TI  - A bioinformatics approach to characterize mammalian selenoprotein T.
AB  - The exact function and trafficking of selenoprotein T (SelT) are still unclear.
      This study was focused on using bioinformatics analysis as an approach to
      understanding the structure-function relationship of SelT and the trafficking of
      SelT between cellular compartments. Blast analysis revealed that SelT is present
      in mammals, birds, frogs, zebra fish, and green algae. Structural analyses
      revealed that SelT contains a CxxU motif in a thioredoxin-like fold, suggesting a
      redox function of SelT. Cysteine (Cys) residues were found in the place of
      selenocysteine in SelT Cys homologs in insects, roundworms, and plants. The
      SignalP program recognized signal peptides in both SelT and SelT Cys homologs.
      Mammalian SelT was predicted to contain an N-terminal signal peptide of 19 amino
      acid residues, which may be involved in targeting SelT to the endoplasmic
      reticulum. Finally, SelT may be localized in the plasma membrane in addition to
      its presence in the Golgi apparatus and the endoplasmic reticulum.

PMID- 22614869
TI  - Altered microRNA expression in cisplatin-resistant ovarian cancer cells and
      upregulation of miR-130a associated with MDR1/P-glycoprotein-mediated drug
      resistance.
AB  - microRNAs (miRNAs) are short non-coding RNA molecules which are involved in the
      regulation of various biological processes. Drug resistance has become a major
      obstacle to successful chemotherapy of ovarian cancer. The aim of this study was
      to investigate microRNA expression profiles in cisplatin-resistant ovarian cancer
      cells and the role of miR-130a in regulating drug resistance. Analysis of
      differentially expressed miRNAs between SKOV3 and SKOV3/CIS cells was assessed by
      miRNA microarrays. Target prediction of miRNAs was determined with the help of
      PicTar or TargetScan. Among these miRNAs, the expression of miR-130a was verified
      using qRT-PCR. The expression of MDR1 mRNA and P-glycoprotein (P-gp) after
      cellular transfection was examined using qRT-PCR and western blotting,
      respectively. Cisplatin sensitivity was detected by the MTT assay. We indentified
      35 downregulated and 54 upregulated miRNAs in SKOV3/CIS compared to those in
      SKOV3. We found that miR-130a was upregulated in SKOV3/CIS compared to the
      parental SKOV3 cells, and PTEN was predicted to be the potential target of miR
      130a. Moreover, downregulation of miR-130a could inhibit MDR1 mRNA and P-gp
      expression and overcome the cisplatin resistance in SKOV3/CIS cells, which
      indicated that miR-130a may be associated with MDR1/P-gp-mediated drug resistance
      and plays the role of an intermediate in drug-resistance pathways of
      PI3K/Akt/PTEN/mTOR and ABC superfamily drug transporters in SKOV3/CIS cells. This
      study provides important information for the development of targeted gene therapy
      for reversing cisplatin resistance in ovarian cancer.

PMID- 22614870
TI  - Nerve conduction and electromyography studies.
AB  - Nerve conduction studies (NCS) and electromyography (EMG), often shortened to
      'EMGs', are a useful adjunct to clinical examination of the peripheral nervous
      system and striated skeletal muscle. NCS provide an efficient and rapid method of
      quantifying nerve conduction velocity (CV) and the amplitude of both sensory
      nerve action potentials (SNAPs) and compound motor action potentials (cMAPs). The
      CV reflects speed of propagation of action potentials, by saltatory conduction,
      along large myelinated axons in a peripheral nerve. The amplitude of SNAPs is in
      part determined by the number of axons in a sensory nerve, whilst amplitude of
      cMAPs reflects integrated function of the motor axons, neuromuscular junction and
      striated muscle. Repetitive nerve stimulation (RNS) can identify defects of
      neuromuscular junction (NMJ) transmission, pre- or post-synaptic. Needle EMG
      examination can detect myopathic changes in muscle and signs of denervation.
      Combinations of these procedures can establish if motor and/or sensory nerve cell
      bodies or peripheral nerves are damaged (e.g. motor neuronopathy, sensory
      ganglionopathy or neuropathy), and also indicate if the primary target is the
      axon or the myelin sheath (i.e. axonal or demyelinating neuropathies). The
      distribution of nerve damage can be determined as either generalised, multifocal
      (mononeuropathy multiplex) or focal. The latter often due to compression at the
      common entrapment sites (such as the carpal tunnel, Guyon's canal, cubital
      tunnel, radial groove, fibular head and tarsal tunnel, to name but a few of the
      reported hundred or so 'entrapment neuropathies').

PMID- 22614871
TI  - Chitooligosaccharides and N-acetyl-D-glucosamine stimulate peripheral blood
      mononuclear cell-mediated antitumor immune responses.
AB  - The aim of the present study was to evaluate the anticancer effects of
      chitooligosaccharides (COS) and N-acetyl-D-glucosamine (NAG), as well as to
      investigate the possible mechanisms involved. MTT assay and flow cytometry were
      used to evaluate the effect of various concentrations of COS and NAG on the
      proliferation and differentiation of peripheral blood mononuclear cells (PBMCs).
      In addition, sarcoma 180 cells were transplanted into mice to establish a tumor
      model. COS and NAG were administered by gavage of various doses. The tumor
      inhibition rate, thymus and spleen indexes, natural killer (NK) cell activity,
      and interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) serum levels were
      detected. Vascular endothelial growth factor (VEGF) expression levels, an
      important marker of angiogenesis, were also detected. As shown by
      immunohistochemistry, VEGF mRNA expression was decreased following treatment with
      COS and NAG, indicating that COS and NAG have an inhibitory effect on the
      expression of VEGF. The results from this study indicate that COS administered at
      a dose of 100 mg/kg and NAG at a dose of 300 mg/kg or 500 mg/kg can not only
      promote the differentiation of PBMCs and the secretion of IL-2 and IFN-gamma, but
      can also inhibit the expression of VEGF mRNA in sarcoma 180 tumors. Our results
      show that the antitumor and immunoregulatory effects of COS and NAG are dose
      dependent. Furthermore, the antitumor effect is achieved by the improvement of
      immunoregulation indirectly.

PMID- 22614872
TI  - Modafinil improves performance in the multiple T-Maze and modifies GluR1, GluR2,
      D2 and NR1 receptor complex levels in the C57BL/6J mouse.
AB  - Modafinil has been shown to modify behavioural and cognitive functions and to
      effect several brain receptors. Effects, however, were not observed at the
      receptor protein complex level and it was therefore the aim of the study to train
      mice in the multiple T-Maze (MTM) as a paradigm for spatial memory and to
      determine paralleling brain receptor complex levels. Sixty C57BL/6J mice were
      used in the study and divided into four groups (trained drug injected; trained
      vehicle injected; yoked drug injected; yoked vehicle injected). Animals obtained
      training for 4 days and were killed 6 h following the last training session on
      day 4. Hippocampi were dissected from the brain, membrane fractions were prepared
      by ultracentrifugation and were run on blue-native gels and immunoblotted with
      antibodies against major brain receptors. Modafinil treatment led to decreased
      latency and increased average speed, but not to changes in pathlength and number
      of correct decisions in the MTM. Drug effects were modifying receptor complexes
      of GluR1, GluR2, D2 and NR1. Training effects on receptor complex levels were
      observed for GluR3, D1 and nicotinic acetylcholine receptor alpha 7 (Nic7). GluR1
      levels were correlating with GluR2 and D1 levels were correlating with D2 and
      NR1. Involvement of the glutamatergic, NMDA, dopaminergic and nicotinergic system
      in modafinil and memory training were herein described for the first time. A
      brain receptor complex pattern was revealed showing the concerted action
      following modafinil treatment.

PMID- 22614873
TI  - Scissors as symbols: disputed ownership of the tools of biomedical obstetrics in
      rural Indonesia.
AB  - In the hands of both traditional and clinic midwives in rural Indonesia a simple
      biomedical tool, umbilical cord scissors, has come to develop a social life that
      symbolizes potential futures. In rural Indonesian villages resources are limited,
      maternal and infant mortality rates are high, and there is robust competition for
      both patients and status between traditional and clinic midwives, all set against
      nationalist pressure to "modernize." The perceived right to use the umbilical
      cord scissors in a professional setting is contested. The folk midwives use the
      umbilical cord scissors to publically reference access to biomedical obstetric
      knowledge, a domain claimed by clinic midwives. This paper explores the way that
      the traditional midwives construct a hybrid modern identity by marking a place
      for traditional and biomedical obstetric systems in the treatment of childbirth.
      Further, this paper argues that traditional midwives use the symbolically laden
      umbilical cord scissors in their attempt to remain locally relevant and to
      circumvent the mission of the clinic programs to eradicate their practice.

PMID- 22614875
TI  - What is the quality of pre-dialysis healthcare in the Czech Republic?
AB  - AIM: The PREPARE study (PRE-dialysis healthcare in PAtients initiating Renal
      rEplacement therapy and its consequences) evaluates the quality of pre-dialysis
      healthcare in patients commencing dialysis treatment in the Czech Republic.
      METHODS: 48% of Czech dialysis centers participating in this prospective
      multicenter observational study provided data on all consecutive patients
      starting renal replacement therapy during 24 weeks. RESULTS: 68% out of 303
      patients had nephrological pre-dialysis care lasting >6 months (57% diabetics).
      Peritoneal dialysis (PD) was chosen by 11.2%. 23.6% of patients were receiving
      erythropoiesis-stimulating agents while the mean hemoglobin level was 98.3 +/
      15.6 g/l. 36.1% of patients were taking phosphate binders while serum phosphates
      reached 1.90 +/-0.61 mmol/l. 64.4% of patients had a functional arteriovenous
      fistula or PD catheter. 91.8% of the patients felt they were well informed about
      hemodialysis and 51.6% about PD. Physicians reported poor compliance of patients
      in 15.1% of cases, while the patients evaluated their own compliance as 9.4%.
      CONCLUSIONS: To conclude: (1) better pre-dialysis care and information are
      needed; (2) higher awareness on PD might increase its low popularity; (3)
      particular attention should be paid to diabetics due to their higher morbidity, a
      lower proportion considered for transplantation and a lower proportion referred
      to nephrologists by diabetologists, and (4) preemptive transplantation should be
      considered more often.

PMID- 22614874
TI  - Impact of clopidogrel and aspirin treatment on the expression of proteins in
      platelets from type-2 diabetic patients with stable coronary ischemia.
AB  - The purpose of this study was to compare the effect of dual antiplatelet therapy
      [clopidogrel + aspirin (ASA)] with respect to ASA on the protein expression of
      platelets from controlled type-2 diabetic patients with stable coronary ischemia.
      Patients had been taking ASA (100 mg day) and they were randomized to receive (n
      = 29) or not (n = 28) 75 mg day clopidogrel for 12 +/- 2 weeks in a blind form.
      Protein expression was analyzed by two-dimensional electrophoresis and mass
      spectrometry. The protein expression of a limited number of proteins such as
      actin-binding protein isotypes 2 and 5, lactate dehydrogenase, serotransferrin
      isotype 4, protein disulfide isomerase-A3 isotype 1, fibrinogen beta chain
      isotype 5, Ras-related protein Rab-7b isotypes 1 and 6, and immunoglobulin heavy
      chain was changed after dual antiplatelet therapy. Plasma level of platelet
      factor 4 (PF4), an in vivo marker of platelet activity, was not different between
      both groups. These changes suggest lower platelet reactivity after dual
      antiplatelet therapy in the studied patients. However, the variation in platelet
      proteome was lower than it would be initially expected, taking into account the
      apparent clinical beneficial effects of dual antiplatelet therapy. PF4 plasma
      level was not further decreased in the platelets treated for a longer time than 9
      12 months with ASA + clopidogrel, as compared with ASA alone.

PMID- 22614876
TI  - The 5th International Conference on Alzheimer's Disease and related disorders in
      the Middle East, 15-17 May 2009, Limassol Cyprus.
AB  - Alzheimer's disease is growing in prevalence worldwide. Though many Western
      countries have developed programs of surveillance and care around Alzheimer's
      disease and dementia, certain regions of the world are beginning to recognize the
      magnitude of the disease burden in the general population. In the Middle East,
      there is growing awareness of the burden of Alzheimer's disease and how it
      impacts health economics, care delivery, and research. Here we summarize the
      proceedings of the 5th International Conference on Alzheimer's Disease in the
      Middle East. We had speakers from 20 countries updating the audience on progress
      toward improving healthcare and research related to AD in this region of the
      world.

PMID- 22614877
TI  - Genetics and expression analysis of the specificity protein 4 gene (SP4) in
      patients with Alzheimer's disease and frontotemporal lobar degeneration.
AB  - Transcription factor Sp4 (Specificity protein 4) levels are increased in the
      brain of patients with Alzheimer's disease (AD), and Sp4 colocalizes with
      neurofibrillary tangles. Moreover, SP4 is a susceptibility gene for bipolar
      disorder and schizophrenia, which share many clinical features with
      frontotemporal lobar degeneration (FTLD). The distribution of three tagging
      single nucleotide polymorphisms(SNPs)-rs9639379, rs10272006, and rs6461569-has
      been determined in a population of 352 patients diagnosed clinically with AD, 290
      patients with FTLD, and 341 age-matched controls. Expression analysis of SP4 was
      performed in peripheral blood mononuclear cells (PBMC). No significant
      differences in either allelic or genotypic frequency of the three SNPs were found
      (p > 0.05), even stratifying according to gender and to the apolipoprotein E
      status. Significantly increased SP4 relative expression levels were observed in
      PBMC from patients with AD as compared with controls (7.132 +/- 1.301 versus
      3.396 +/- 0.829, p < 0.050) and a similar trend was shown in patients with FTLD
      compared with controls (6.525 +/- 1.500 versus 3.396 +/- 0.829, p = 0.073).
      According to these results, SP4 gene does not act as a susceptibility factor
      either for AD or FTLD. However, Sp4 mRNA levels are upregulated in patients,
      possibly resulting in an aberrant expression of downstream target genes involved
      in the pathogenesis of both diseases.

PMID- 22614878
TI  - A novel subject synchronization clinical trial design for Alzheimer's disease.
AB  - One of the challenges in developing a viable therapy for Alzheimer's disease has
      been demonstrating efficacy within a clinical trial. Using this as motivation, we
      sought to re-examine conventional clinical trial practices in order to determine
      whether efficacy can be better shown through alternative trial designs and novel
      analysis methods. In this work, we hypothesize that the confounding factors which
      hamper the ability to discern a treatment signal are the variability in
      observations as well as the insidious nature of the disease. We demonstrate that
      a two-phase trial design in which drug dosing is administered after a certain
      level of disease severity has been reached, coupled with a method to account more
      accurately for the progression of the disease, may allow us to compensate for
      these factors, and thus enable us to make treatment effects more apparent.
      Utilizing data from two previously failed trials which involved the evaluation of
      galantamine for indication in mild cognitive impairment, we were able to
      demonstrate that a clear treatment effect can be realized through both visual and
      statistical means, and propose that future trials may be more likely to show
      success if similar methods are utilized.

PMID- 22614879
TI  - A rating scale for gait evaluation in cognitive deterioration (RSGE-CD):
      validation study.
AB  - A relationship between decline in mobility and walking performance and cognitive
      impairment exists in the elderly. Therefore, clinical assessment of gait and
      mobility may be relevant for diagnostic and therapeutic purposes. However, the
      rating scales used for evaluation of gait disorder in the context of cognitive
      deterioration were not designed or validated for that setting. The present study
      was aimed at checking the clinimetric properties of the Rating Scale for Gait
      Evaluation in Cognitive Deterioration (RSGE-CD), specifically developed for
      assessment of gait dysfunction across all stages of cognitive decline. Two
      hundred fifty six subjects were included in the study and classified according to
      the Global Deterioration Scale (control, subjective/mild cognitive impairment, or
      dementia). Patients with dementia had a diagnosis of probable Alzheimer's disease
      (73%) or dementia of combined etiology (27%). Cognitive and functional
      evaluations, the Tinetti scale, and timed tests were simultaneously applied with
      the tested scale, which is composed of two subscales: Functional ability and
      Examination. Exploratory factor analysis showed one factor (70% of the variance).
      Floor effect and skewness were observed in the control group, whereas internal
      consistency (Cronbach's alpha = 0.88-0.95), inter-observer and test-retest
      reliability (intraclass correlation coefficients >= 0.97) were satisfactory.
      Convergent validity with the other measures was >= 0.60 and the discriminant
      validity according to classification of subjects by cognitive state and other
      aspects was also satisfactory (p = 0.0001). The RSGE-CD showed low standard
      errors of measurement. In this first validation study, the RSGE-CD showed
      satisfactory clinimetric attributes for assessing gait and mobility across the
      complete range of cognitive state.

PMID- 22614880
TI  - Prolonged back pain attributed to suspected spondylodiscitis. The value of 18F
      FDG PET/CT imaging in the diagnostic work-up of patients.
AB  - OBJECTIVE: This study aimed at investigating the diagnostic value of 18F-FDG
      PET/CT in cases of suspected spondylodiscitis after inconclusive results in
      initial diagnostic imaging. PATIENTS, METHODS: We analysed 38 consecutive cases
      of suspected spondylodiscitis (mean age: 67 +/- 14 years) with chronic back pain
      referred to our Department during a four-year-period after inconclusive results
      in MRI or other conventional modalities. Clinical histories were retrospectively
      worked up and results of 18F-FDG PET/CT and MRI were analysed and related to the
      results of biopsy, blood culture and a one-year clinical follow-up. 18F-FDG
      PET/CT was analysed qualitatively by visual analysis and quantitatively. We
      measured the maximum standardized uptake value (SUV(max)) in the region of back
      pain and in a corresponding reference region (RR) in each patient and calculated
      a SUV(max-ratio). RESULTS: 22/38 patients had confirmed spondylodiscitis, while
      16 were negative. 18F-FDG PET/CT established a correct diagnosis in 34 out of 38
      patients by visual analysis. 18F-FDG PET/CT reached a sensitivity, specificity
      and accuracy of 81.8%, 100%, 89.5% and a PPV and NPV of 100% and 80%. MRI,
      performed in 27 patients reached a sensitivity, specificity and accuracy of 75%,
      71.4%, 74.1% and a PPV and NPV of 88.2% and 50%. Patients with confirmed
      spondylodiscitis showed a significantly (p < 0.05) higher SUV(max) of 5.1 +/- 1.9
      and SUV(max)-ratio of 1.9 +/- 0.8 than patients without it (SUV(max) (3.8 +/-
      1.5), SUV(max-ratio) (1.2 +/- 0.3). CONCLUSION: 18F-FDG PET/CT provided
      diagnostic information in most patients with chronic back pain and suspected
      spondylodiscitis. It was helpful in establishing a correct diagnosis in
      challenging cases of spondylodiscitis with mostly unclear findings in previous
      MRI.

PMID- 22614881
TI  - Association of amphiregulin with the cetuximab sensitivity of gastric cancer cell
      lines.
AB  - The therapeutic activity of the epidermal growth factor receptor (EGFR)-directed
      monoclonal antibody cetuximab in gastric cancer is currently being investigated
      in clinical studies. Reliable biomarkers for the identification of patients who
      are likely to benefit from this treatment are not available. In this study, we
      assessed the activity of cetuximab in five gastric cancer cell lines (AGS, AZ521,
      Hs746T, LMSU and MKN1). The viability of two of these cell lines, AZ521 and MKN1,
      was significantly reduced by cetuximab treatment. High expression and secretion
      levels of the EGFR-binding ligand, amphiregulin (AREG), were associated with
      cetuximab responsiveness. MET activation and mutations in Kirsten-Ras gene (KRAS)
      were associated with cetuximab resistance. By introducing a hierarchy between
      these markers, we established a model that facilitated the correct classification
      of all five gastric cancer cell lines as cetuximab responsive or non-responsive.
      The highest priority was allocated to activating KRAS mutations, followed by MET
      activation and finally by the levels of secreted AREG. In order to validate these
      results, we used three additional human gastric cancer cell lines (KATOIII, MKN28
      and MKN45). In conclusion, we propose that our model allows the response of
      gastric cancer cell lines to cetuximab treatment to be predicted.

PMID- 22614882
TI  - Brief Report: long-term outcome of a randomized clinical trial comparing
      methotrexate to cyclophosphamide for remission induction in early systemic
      antineutrophil cytoplasmic antibody-associated vasculitis.
AB  - OBJECTIVE: The NORAM (Nonrenal Wegener's Granulomatosis Treated Alternatively
      with Methotrexate [MTX]) trial demonstrated that MTX can replace cyclophosphamide
      (CYC) as remission-inducing treatment for patients with newly diagnosed early
      systemic antineutrophil cytoplasmic antibody-associated vasculitis. Duration of
      relapse-free survival was longer among CYC-treated patients than among MTX
      treated patients during short-term followup. The aim of the present study was to
      describe the long-term outcome in patients enrolled in the randomized clinical
      trial. METHODS: Outcome questionnaires were sent to investigators who had
      recruited patients for the NORAM trial. Patients treated with MTX for induction
      of remission (n = 49) were compared to CYC-treated patients (n = 46) with respect
      to immunosuppressive therapy during followup, relapse-free survival, mortality,
      and occurrence of other clinical events. RESULTS: The median duration of followup
      was 6 years (range 0.1-10.8 years). One patient developed end-stage renal
      disease, and 11 died. The number of patients affected by serious infection,
      malignancy, or severe organ failure did not differ between treatment groups, and
      no difference in survival rate was observed. The duration of corticosteroid
      therapy was longer in the MTX group during the 18 months of the trial (P =
      0.005). During subsequent followup, patients who were in the MTX group in the
      NORAM trial received corticosteroids, CYC, and other immunosuppressive agents
      (azathioprine, MTX, and/or mycophenolate mofetil) for longer periods than those
      who were in the CYC group (P = 0.004, P = 0.037, and P = 0.031, respectively).
      The cumulative relapse-free survival tended to be lower in the MTX group (P =
      0.056). CONCLUSION: In the NORAM cohort, no difference in occurrence of major
      adverse events was observed between treatment groups during long-term followup.
      However, first-line treatment with MTX was associated with less effective disease
      control than CYC-based induction therapy.

PMID- 22614883
TI  - Gold nanoparticle-modulated conductivity in gold peapodded silica nanowires.
AB  - We report the enhanced electrical conductivity properties of single gold
      peapodded amorphous silica nanowires synthesized using microwave plasma enhanced
      chemical vapor deposition. Dark conductivity of the gold-peapodded silica
      nanowires can be adjusted by controlling the number of incorporated metal
      nanoparticles. The temperature-dependent conductivity measurement reveals that
      the band tail hopping mechanism dominates the electron transport in the gold
      peapodded silica nanowires. The high conductivity in the nano-peapodded nanowires
      with more embedded gold-nanoparticles can be explained by the higher density of
      hopping states and shorter hopping distance. These Au-embedded amorphous silica
      nanowires have provided a new approach to enhance not only the electron
      conduction, but also the chemical-sensor response/sensitivity.

PMID- 22614884
TI  - Comparison of the IHC, FISH, SISH and qPCR methods for the molecular diagnosis of
      breast cancer.
AB  - Her2 proto-oncogene amplification and protein overexpression is observed in 20
      40% of patients with breast cancer and plays a crucial role in invasive breast
      cancer and its treatment. In the present study, we investigated samples from 131
      patients with invasive breast carcinoma. In all cases, the
      overexpression/amplification level of Her2 was determined using manual
      immunohistochemistry (IHC) and/or automatic IHC, fluorescence in situ
      hybridization (FISH), silver in situ hybridization (SISH) and quantitative
      polymerase chain reaction (qPCR). Using various methods, we demonstrated
      candidate methods for Her2 detection and their dependability. Our results
      demonstrate that these methods are highly comparable for the detection of Her2
      overexpression/amplification. It was also revealed that qPCR is a valuable tool
      for the evaluation of Her2 gene overexpression/amplification. The results from
      pPCR analysis positively correlated with the results from IHC and FISH analysis.
      Moreover, in contrast to IHC or SISH/FISH, the results obtained by qPCR were not
      encumbered with any subjective error on the part of the evaluator.

PMID- 22614885
TI  - Immunological and virological responses to cART in HIV/HBV co-infected patients
      from a multicenter cohort.
AB  - OBJECTIVE: To evaluate the influence of hepatitis B virus (HBV) coinfection on
      immunological, virological and clinical responses to lamivudine (3TC)-based
      combined antiretroviral therapy (cART) in Chinese patients. DESIGN AND METHODS:
      This prospective, multicenter cohort study recruited 529 antiretroviral-naive
      participants (aged 18-65 years, both sexes) between 2008 and 2010.They were
      grouped by HBV serostatus. Virological and immunological responses were monitored
      at baseline and week 4, 8, 12, 24, 36 and 48. cART for all patients was
      nevirapine, 3TC with either zidovudine or stavudine. RESULTS: First, HIV/HBV
      coinfection rate in our cohort was 14.6%. Second, among 508 patients with
      complete baseline information, median CD4 level was significantly lower in the
      chronic HBV-infected (CHB) group and isolated core group. In the CHB
      group,hepatitis B e antigen positivity rather than HBV DNA level was associated
      with lower CD4 cell count. Third, in the isolated core group, occult infection
      rate was 9.5%.Fourth, at week 48, rate of HIV suppression below 40 copies/ml was
      74.2%. Median increase in the CD4 cell count at week 48 was 127 cells/ml. Of
      note, HBV serostatus did not influence virological and immunological response to
      cART at each follow-up time point. Although HBV serostatus was associated with
      different alanine aminotransferase levels during follow-up, hepatitis and
      hyperbilirubinemia rates were not significantly different. Fifth, the 3TC-based
      regimen was efficacious against HBV replication, with median decrease in HBV DNA
      of 2.87 log copies/ml. However, hepatitis B e antigen positivity was associated
      with poorer HBV DNA suppression. CONCLUSION: In our cohort, CHB infection and
      isolated hepatitis B core antibody positivity were related to faster HIV
      progression. Despite of this, virological and immunological responses were not
      affected by HBV serostatus.

PMID- 22614886
TI  - Early antiretroviral therapy improves neurodevelopmental outcomes in infants.
AB  - OBJECTIVES: To evaluate the effect of early versus deferred antiretroviral
      therapy (ART) on the neurodevelopment of infants from Cape Town participating in
      the Children with HIV Early Antiretroviral Therapy (CHER) trial. DESIGN: HIV
      infected infants were randomized to early (<3 months) or deferred ART. HIV
      uninfected infants (HIV-exposed and HIV-unexposed) provide background data.
      METHODS: Neurological examination and Griffiths Mental Development Scales (GMDS)
      were administered between 10-16 months of age by testers blind to HIV status and
      randomized allocation. Mean quotients were compared using paired Student's t
      tests. RESULTS: Sixty-four infants on early ART and 26 on deferred ART (of
      potential 77 and 38 respectively on CHER trial) were assessed at median age 11
      months (range 10-16). On the GMDS, all scores were lower in the deferred arm and
      the General Griffiths and Locomotor Scores were significantly lower: mean (SD)
      =100.1 (13.8) vs. 106.3 (10.6) P=0.02; and 88.9 (16.3) vs. 97.7 (12.5), P<0.01,
      respectively. Children with HIV who received early ART performed as well as
      children without HIV except on the Locomotor subscale. Both infected and
      uninfected mean GMDS scores were within the average range. CONCLUSION: Infants
      initiated on early ART have significantly better Locomotor and general scores on
      the GMDS at median age 11 months compared to infants on deferred ART, despite
      careful monitoring and ready access to ART in the latter.

PMID- 22614887
TI  - Reclassification of risk of death with the knowledge of D-dimer in a cohort of
      treated HIV-infected individuals.
AB  - OBJECTIVE: To evaluate the change in categories of risk of death by adding D
      dimer to conventional mortality risk factors. DESIGN: Cohort study. METHODS: Data
      on HIV-infected participants receiving standard combination antiretroviral
      therapy in two clinical trials (Evaluation of Subcutaneous Proleukin in a
      Randomized International Trial and Strategic Management of antiretroviral
      therapy), who had baseline D-dimer measured, were randomly split into two equal
      training and a validation datasets. A multivariable survival model was built
      using the training dataset and included only conventional mortality risk factors
      measured at baseline. D-dimer was added to create the comparison model. The level
      of reclassification of mortality risk, for those with at least 5-years of follow
      up, was then assessed by tabulating mortality risk defined as low (<=2% predicted
      rate), moderate (2-5%) or high (>5%). Reclassification analyses were then
      repeated on the validation dataset. RESULTS: The analysis population at baseline
      had a mean age of 43 years, median CD4(+) cell count of 535 cells/MUl (IQR: 420
      712), and 83% had HIV RNA of at least 500 copies/ml. In the training dataset
      (n=1946, 8939 person-years), there were 83 deaths at a rate of 0.93 per 100
      person-years. Addition of D-dimer to the reference model resulted in 6% or fewer
      (P>0.05) being correctly reassigned, either up or down, to a new risk category,
      in both, training and validation datasets. The integrated discrimination
      improvement in training and validation datasets was 0.60% (P=0.084) and 0.45%
      (P=0.168), respectively. CONCLUSION: In this relatively well population, at the
      given risk cutoffs, D-dimer appeared to only modestly improve the discernment of
      risk. Risk reclassification provides a method for assessing the clinical utility
      of biomarkers in HIV cohort studies.

PMID- 22614888
TI  - The HIV care continuum:  no partial credit given.
AB  - Despite significant scale-up of HIV care and treatment across the world, overall
      effectiveness of HIV programs is severely undermined by attrition of patients
      across the HIV care continuum, both in resource-rich and resource-limited
      settings. The care continuum has four essential steps: linkage from testing to
      enrollment in care, determination of antiretroviral therapy (ART) eligibility,
      ART initiation, and adherence to medications to achieve viral suppression. In
      order to substantially improve health outcomes for the individual and potentially
      for prevention of transmission to others, each of the steps of the entire care
      continuum must be achieved. This will require the adoption of interventions that
      address the multiplicity of barriers and social contexts faced by individuals and
      populations across each step, a reconceptualization of services to maximize
      engagement in care, and ambitious evaluation of program performance using all-or
      none measurement.

PMID- 22614890
TI  - Active myofascial trigger points might be more frequent in patients with cervical
      radiculopathy.
AB  - BACKGROUND: Myofascial trigger points (MTrPs) are commonly observed in the neck,
      parascapular region, and upper back muscles of patients with cervical pathology.
      AIM: To assess the frequency of latent and active myofascial trigger point
      (aMTrP) in the neck and upper back muscles in patients with cervical
      radiculopathy and healthy subjects. DESIGN: Controlled clinical trials. SETTING:
      Outpatients and controls. POPULATION: Two hundred and forty four patients and 122
      controls METHODS: The patients clinically diagnosed as cervical radiculopathy
      with positive Spurling's test and confirmed by MRI, were enrolled in this study.
      All subjects were examined for active and latent MTrP. In patients with cervical
      radiculopathy, an aMTrP was distinguished from a latent one when the referred
      pain elicited by exploration of the MTrP is recognized as familiar. RESULTS: The
      patients comprised of 128 female (52.5%) and 116 male (47.5%) patients. Mean age
      was 44.58(20-65 years). In 125 (51.2%) of patients with cervical radiculopathy
      were found an aMTrP at least one muscle from upper trapezius, multifidus,
      splenius capitis, levator scapulae, rhomboid major, minor and deep paraspinal
      muscles. Number and distribution of MTrPs in patients with 244 cervical
      radiculopathy and in healthy controls. aMTrPs were detected most common in
      levator scapula (16.3%), splenius capitis (14.7%), rhomboid minor (14.3%), upper
      part of trapezius (13.5%), rhomboid major (10.2%) and multifidus (8.6%) muscles.
      Patients with cervical radiculopathy showed latent MTrP in levator scapula (27%),
      splenius capitis (16.8%), rhomboid minor (24.6%), upper part of trapezius
      (33.2%), rhomboid major (9%) and multifidus (8.2%) muscles. There was significant
      difference in terms of distribution of active and latent MTrPs in patients with
      cervical radiculopathy (P=0.019). Number of latent MTrPs in upper trapezius
      muscles in patients with cervical radiculopathy was more than the expected
      distribution. None of the subjects of control group had aMTrP. However, healthy
      controls showed latent MTrP in levator scapula (33.6%), splenius capitis (16.4%),
      rhomboid minor (21.3%), upper part of trapezius (40.2%), rhomboid major (6.5%)
      and multifidus (17.2%) muscles. There was no significant difference in terms of
      distribution of latent MTrPs between cervical radiculopathy and control groups
      (P=0.249). The frequency of aMTrP was found to be significantly higher in CDH
      with median localization as compared to posterolateral herniations (P=0.041).
      After conservative treatment for two weeks, number of patients with active MTrP
      in cervical radiculopathy were decreased about 50%. CONCLUSION: Cervical root
      compression would be considered as the starting or maintaining factor of aMTrP.
      CLINICAL REHABILITATION IMPACT: The treatment of cervical radiculopathy might be
      facilitated the improving in aMTrPs located in aforementioned muscles.

PMID- 22614889
TI  - Cerebrospinal fluid HIV escape associated with progressive neurologic dysfunction
      in patients on antiretroviral therapy with well controlled plasma viral load.
AB  - OBJECTIVE: To characterize HIV-infected patients with neurosymptomatic
      cerebrospinal fluid (CSF) 'escape', defined as detectable CSF HIV RNA in the
      setting of treatment-suppressed plasma levels or CSF RNA more than 1-log higher
      than plasma RNA. DESIGN: Retrospective case series. SETTING: Four urban medical
      centers in the United States and Europe. PARTICIPANTS: Virologically controlled
      HIV-infected patients on antiretroviral therapy (ART) with progressive neurologic
      abnormalities who were determined to have CSF 'escape'. INTERVENTION Optimization
      of ART based upon drug susceptibility and presumed central nervous system
      exposure. MAIN OUTCOME MEASURES: Levels of CSF HIV RNA and inflammatory markers,
      clinical signs and symptoms, and MRI findings. RESULTS: Ten patients presented
      with new neurologic abnormalities, which included sensory, motor, and cognitive
      manifestations. Median CSF HIV RNA was 3900 copies/ml (range 134-9056), whereas
      median plasma HIV RNA was 62 copies/ml (range <50 to 380). Median CD4 T-cell
      count was 482 cells/MUl (range 290-660). All patients had been controlled to less
      than 500 copies/ml for median 27.5 months (range 2-96) and five of 10 had been
      suppressed to less than 50 copies/ml for median 19.5 months (range 2-96).
      Patients had documentation of a stable ART regimen for median 21 months (range 9
      60). All had CSF pleocytosis or elevated CSF protein; seven of eight had
      abnormalities on MRI; and six of seven harbored CSF resistance mutations.
      Following optimization of ART, eight of nine patients improved clinically.
      CONCLUSION: The development of neurologic symptoms in patients on ART with low or
      undetectable plasma HIV levels may be an indication of CSF 'escape'. This study
      adds to a growing body of literature regarding this rare condition in well
      controlled HIV infection.

PMID- 22614891
TI  - Cortical plasticity and brain computer interface.
AB  - There is increasing evidence to support the concept that adult brain has the
      remarkable ability to plastically reorganize itself. Brain plasticity involves
      distinct functional and structural components and plays a crucial role in
      reorganizing central nervous system's networks after any lesion in order to
      partly or totally restore lost and/or compromised functions. The idea that a
      computer can decode brain electromagnetic signals to infer the intentions of a
      human and then enact those intentions directly through a machine is becoming a
      reasonable technical possibility. In neurological patients unable to move and to
      communicate with the external environment, technologies implementing brain
      machine interfaces (BMIs) can be of valuable aid and support. The emerging
      possibility, through neuro-imaging advanced techniques, to clarify some crucial
      issues underlying brain plasticity will give the possibility to modulate these
      mechanisms in a BCI-oriented way. This approach may have a tremendous impact in a
      variety of neuropsychiatric disorders and the clinical advent of this technology
      will usher in a new era of restorative medicine.

PMID- 22614892
TI  - Robotic technology and physical medicine and rehabilitation.
AB  - In this opinion piece, I will revisit the basis for our belief that robotic
      manipulation is a valid approach to promote speedier and better recovery
      following a stroke and discuss some of the clinical evidence that led to the
      September 2010 guidelines for stroke care of the American Heart Association as
      well as the December 2010 guidelines of the Veterans Administration endorsing the
      use of robotic technology for the upper extremity (UE) but not for the lower
      extremity (LE) post-stroke rehabilitation effort.

PMID- 22614893
TI  - Therapeutic ultrasound for acute ankle sprains.
AB  - BACKGROUND: Ultrasound is used in the treatment of a wide variety of
      musculoskeletal disorders, which include acute ankle sprains. AIM: To evaluate
      the effects of ultrasound therapy in the treatment of acute ankle sprains.
      METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised
      Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE
      until September 2010, CINAHL (until 2004), and PEDro (accessed 01/06/09). (Quasi)
      randomised trials were included if the following conditions were met: at least
      one study group was treated with therapeutic ultrasound; participants had acute
      lateral ankle sprains; and outcome measures included general improvement, pain,
      swelling, functional disability, or range of motion. Risk ratios and risk
      differences with 95% confidence intervals were calculated for dichotomous
      outcomes and mean differences with 95% confidence intervals for continuous
      outcome measures. Limited pooling of data was undertaken where there was clinical
      homogeneity in terms of participants, treatments, outcomes, and follow-up time
      points. RESULTS: Six trials were included, involving 606 participants. Five
      trials included comparisons of ultrasound therapy with sham ultrasound; and three
      trials included single comparisons of ultrasound with three other treatments.
      None of the five placebo-controlled trials (sham ultrasound) demonstrated
      differences between true and sham ultrasound therapy for any outcome measure at
      one to four weeks of follow-up. The pooled risk ratio for general improvement at
      one week was 1.04 (random-effects model, 95% confidence interval 0.92 to 1.17)
      for active versus sham ultrasound. The differences between intervention groups
      were generally small, between 0% and 6%, for most dichotomous outcomes.
      CONCLUSION: The evidence from the five small placebo-controlled trials included
      in this review does not support the use of ultrasound in the treatment of acute
      ankle sprains. The potential treatment effects of ultrasound appear to be
      generally small and probably of limited clinical importance, especially in the
      context of the short-term recovery period in most people with these injuries.
      However, the available evidence is insufficient to rule out the possibility that
      there is an optimal dosage schedule for ultrasound therapy that may be of
      benefit.

PMID- 22614895
TI  - Retractions: trends, implications, and possible further steps.

PMID- 22614896
TI  - Study of the correlation of imipenem resistance with efflux pumps AdeABC, AdeIJK,
      AdeDE and AbeM in clinical isolates of Acinetobacter baumannii.
AB  - BACKGROUND: To investigate the role of efflux pumps AdeABC, AdeIJK, AdeDE and
      AbeM in reduced susceptibility to imipenem in clinical isolates of Acinetobacter
      baumannii. METHODS: Susceptibility testing was conducted by the agar dilution
      method. The presence and expression of pump genes were analyzed by conventional
      PCR and real-time RT-PCR, respectively. RESULTS: Most antibiotics, including
      carbapenem, aminoglycosides, fluoroquinolones and cephalosporins showed high
      minimum inhibitory concentration (MIC) values in imipenem-resistant A. baumannii
      (IRAB). After exposure to the efflux pump inhibitor Phe-Arg-beta-naphthylamide, a
      4- to 32-fold reduction of imipenem MICs was observed in 33 (66%) isolates of
      IRAB, while no significant decrease occurred in imipenem-susceptible A. baumannii
      (ISAB). The majority of IRAB isolates (>80%) were found to be positive for adeB,
      adeR, adeS, adeJ and abeM. Positive adeE was discovered in 6 isolates of IRAB and
      coexisted with adeB. Approximate 4-, 3- and 11-fold increases in adeB, adeJ and
      abeM expression were observed, respectively, in IRAB compared to those in ISAB.
      CONCLUSIONS: A variety of efflux pump systems, including AdeABC, AdeIJK and AbeM,
      seem to play important roles in the resistance to imipenem of A. baumannii.
      Moreover, this is the first time that adeE has been found to coexist with adeB in
      a small number of isolates of A. baumannii.

PMID- 22614897
TI  - Superior uptake and outcomes of early infant diagnosis of HIV services at an
      immunization clinic versus an "under-five" general pediatric clinic in Malawi.
AB  - OBJECTIVE: Although the Malawian government recommends HIV-exposed infants
      receive early infant diagnosis (EID) of HIV at "under-five" pediatric clinics
      (U5Cs), most never enroll. Therefore, we evaluated the integration of EID testing
      into an immunization clinic (IC) compared with the current standard of EID
      testing at an U5C. DESIGN: Prospective observational study. METHODS: Using
      routine provider-initiated HIV testing and counseling (PITC) registers, we
      prospectively studied 1757 children offered PITC at a government IC and U5C.
      Infants tested by HIV DNA polymerase chain reaction (PCR) were followed until PCR
      result disclosure or defaulting. RESULTS: We sampled 877 and 880 consecutive PITC
      recipients at U5C and IC, respectively. Overall, a 7-fold greater proportion
      received PITC at IC (84.2% vs. 11.4%, P < 0.001). PITC recipients at IC were more
      than 14 months younger (2.6 vs. 17.0, P < 0.001), with greater proportions HIV
      exposed (17.6% vs. 5.3%, P < 0.001) and PCR eligible (7.9% vs. 3.5%, P < 0.001).
      A higher percentage of IC infants accepted PCR testing (100.0% vs. 90.3%, P =
      0.03). Additionally, IC PCR recipients were 2.5 months younger (3.1 vs. 5.6, P <
      0.001) with 4 times less testing PCR positive (7.1% vs. 32.1%, P < 0.001).
      Importantly, a more than 3-fold greater proportion of HIV-exposed infants at IC
      returned for their PCR result and enrolled into care (78.6% vs. 25.0%, P <
      0.001). CONCLUSIONS: Compared with an U5C, integrating EID testing into an IC is
      more acceptable, more feasible, enrolls more infants into EID at younger ages,
      and would likely strengthen Malawi's EID services if expanded.

PMID- 22614898
TI  - Single- and multiple-dose pharmacokinetics of darunavir plus ritonavir and
      etravirine in semen and rectal tissue of HIV-negative men.
AB  - BACKGROUND: Antiretroviral therapy has become a central component of combination
      in HIV prevention efforts. Defining the individual exposure of commercially
      available antiretroviral therapy in genital secretions and vulnerable mucosal
      tissues is paramount to designing future prevention interventions. METHODS: A
      pharmacokinetic (PK) study was performed in 12 HIV-negative men receiving 600 mg
      of darunavir, 100 mg of ritonavir, and 200 mg of etravirine orally, twice daily
      for 8 days. Seven blood plasma (BP) samples were collected over 12 hours on day 1
      (PK1) and days 7 and 8 (PK2). One rectal tissue (RT) sample from each subject was
      collected during PK1 and PK2. During PK1, 2 seminal plasma (SP) samples were
      collected from each subject. During PK2, 6 SP samples were collected from each
      subject over 2 days. RESULTS: Antiretrovirals were detected in SP and RT within 1
      hour after a single dose. Over PK1 and PK2, SP exposures were lower than BP by
      80%-92% (DRV), 89-95% (RTV), and 83-88% (ETR). However, protein binding in SP
      (14% for darunavir, 70% for ritonavir, and 97% for etravirine) was lower than in
      BP. Rectal tissue exposures were higher than BP by 39- to 155-fold for darunavir,
      12- to 61-fold for ritonavir, and 20- to 40-fold for etravirine. CONCLUSIONS:
      Lower SP protein binding resulted in higher pharmacologically active darunavir
      and etravirine concentrations compared with BP. High RT concentrations may also
      be favorable for suppressing viral replication in the gastrointestinal mucosa.
      The high protein-unbound exposures in SP and total exposures in RT support
      further investigations of darunavir plus ritonavir and etravirine in secondary
      prevention.

PMID- 22614900
TI  - T-cell subset distribution in HIV-1-infected patients after 12 years of treatment
      induced viremic suppression.
AB  - OBJECTIVE: Residual immune activation and skewed T cell maturation may contribute
      to excess comorbidity and mortality in successfully treated HIV-infected
      patients, and long-term effects of combination antiretroviral therapy (cART) on
      immune reconstitution remain a debated issue. Quantitative T cell reconstitution
      and activation and its association with residual viremia in patients with 12
      years of viremic suppression were investigated. DESIGN: Blood samples collected
      cross-sectionally from 71 HIV-infected patients with cART-induced viremic
      suppression through 12 years were compared with samples from 16 healthy controls.
      METHODS: Several different subsets of naive, memory, and activated T cells were
      analyzed in fresh whole blood by 6-color flowcytometry, and ultrasensitive
      quantification of HIV RNA was performed. RESULTS: HIV-infected patients had lower
      absolute and relative CD4 T cell counts and higher absolute and relative CD8 T
      cell counts than controls. HIV-infected patients had lower concentrations of
      naive CD4 cells than controls, but proportions were similar. HIV-infected
      patients had higher concentrations of CD8 T cells than controls in all the
      examined subsets but only a higher proportion of CD8 cells in the intermediately
      differentiated and activated subsets. Residual viremia did not correlate to
      proportions of naive CD4, CD4 recent thymic emigrants, or activated CD8 T cells.
      CONCLUSIONS: This study demonstrated some degree of T cell imbalance even after
      12 years of successful cART. Large longitudinal studies are needed to establish
      whether these discrete changes have clinical relevance.

PMID- 22614899
TI  - Stavudine concentrations in women receiving postpartum antiretroviral treatment
      and their breastfeeding infants.
AB  - First-line antiretroviral treatment regimens in resource-limited settings used in
      breastfeeding mothers often include stavudine (d4T). Limited data describing d4T
      concentrations in breast milk are available. We analyzed d4T concentrations in 52
      mother-infant pairs using ultra-performance liquid chromatography-tandem mass
      spectrometry (lower limit of quantification: 5 ng/mL in plasma, 20 ng/mL in
      breast milk). Median (interquartile range) d4T concentrations were 86 (36-191)
      ng/mL in maternal plasma, 151 (48-259) ng/mL in whole milk, 190 (58-296) ng/mL in
      skim milk, and <5 (<5 to <5) ng/mL in infant plasma. Although d4T is concentrated
      in breast milk relative to maternal plasma, the infant d4T dose received from
      breast milk is very small and not clinically significant.

PMID- 22614901
TI  - Prenatal evaluation and management of fetuses exposed to Anti-SSA/Ro antibodies.
AB  - Maternal anti-SSA antibodies are common, existing in up to 2 % of the general
      population. Fetuses exposed to these antibodies are at risk for both cardiac and
      noncardiac complications. The cardiac complications include arrhythmias,
      structural disease, and cardiomyopathy. Although rare, the cardiac disease
      associated with these antibodies is permanent and severe. Current fetal
      echocardiographic screening tools are nonspecific. The type and frequency of
      screening needed is controversial. Although promising transplacental treatment
      strategies exist, prospective randomized studies are lacking. Dexamethasone, the
      medication used most frequently, imposes significant risks to both mother and
      fetus. This report presents a discussion of the at-risk population, the spectrum
      of fetal cardiac disease associated with maternal anti-SSA antibodies, the
      current fetal echocardiographic screening tools, the therapeutic options, and the
      management and delivery planning strategies. With appropriate prenatal follow-up,
      assessment, and delivery planning, even high-risk fetuses can be delivered safely
      and managed effectively.

PMID- 22614903
TI  - Transcatheter repair of partial anomalous pulmonary venous drainage using an
      amplatzer vascular plug in a postoperative patient with tetralogy of Fallot.
AB  - The association of tetralogy of Fallot with a partial anomalous pulmonary vein is
      rare. Although this combination is generally treated with surgery, in this paper
      we present the case of an 8-year-old boy whose anomalous venous drainage was
      successfully closed with an Amplatzer vascular plug after a total correction of a
      tetralogy of Fallot. The patient was asymptomatic at his last follow-up.

PMID- 22614902
TI  - Prenatal diagnosis of isolated levocardia and a structurally normal heart: two
      case reports and a review of the literature.
AB  - Isolated levocardia (ILC) is a developmental abnormality involving an abnormal
      abdominal situs with a normal cardiac situs. This abnormality is especially rare
      when it is associated with a normal cardiac anatomy. The prenatal diagnoses of
      seven cases were reported in the English literature. This report presents two
      cases referred to the authors' echocardiography laboratory for maternal diabetes
      mellitus in case 1 and suspected dextrocardia in case 2. In both cases, ILC with
      a structurally normal heart was diagnosed prenatally. The child in the first case
      was found to have a normal inferior vena cava (IVC) prenatally. Postnatally, he
      was found to have intestinal malrotation with duodenal obstruction and multiple
      splenules. Interruption of the IVC was shown by abdominal ultrasound. The child
      in the second case was found to have an interrupted IVC with azygos continuation
      prenatally. Postnatally, intestinal malrotation with no evidence of intestinal
      obstruction or asplenia was detected. Neither of the cases had reported cardiac
      arrhythmias. Early diagnosis is crucial in these cases due to the high incidence
      of associated anomalies and potential life-threatening conditions. Management of
      patients with ILC is dictated by the associated anomalies. Long-term follow-up
      assessment is recommended for these patients to monitor the development of rhythm
      abnormalities.

PMID- 22614904
TI  - Natural history of conduction abnormalities in a patient with Kearns-Sayre
      syndrome.
AB  - Kearns-Sayre syndrome is a rare mitochondrial disorder characterized by large
      scale deletion or rearrangement of mitochondrial DNA, which is usually not
      inherited but occur spontaneously probably at the germ cell level or very early
      in embryonic development by Mehndiratta et al. (Neurol India 50:162-167, 2002).
      Neuromuscular and cardiac conduction abnormalities are most commonly involved in
      these patients, which may have subtle presenting signs.

PMID- 22614905
TI  - Pulmonary interstitial glycogenosis: an unrecognized etiology of persistent
      pulmonary hypertension of the newborn in congenital heart disease?
AB  - BACKGROUND: Pulmonary interstitial glycogenosis (PIG) arises from a developmental
      disorder of the pulmonary mesenchyme and presents clinically with reversible
      neonatal respiratory distress and/or persistent pulmonary hypertension of the
      newborn (PPHN). OBJECTIVE: We report two cases of PIG in patients with congenital
      heart disease (CHD) and evidence of PPHN. RESULTS: Both cases demonstrated the
      hallmark PIG histologic finding of diffuse, uniform interstitial thickening due
      to the presence of immature interstitial cells containing abundant cytoplasmic
      glycogen. CONCLUSIONS: We report the second and third patients with PIG
      associated with CHD. Because histologic examination is required to establish the
      diagnosis, we speculate that PIG, although rare, may be underrecognized in
      neonates presenting with PPHN in the setting of CHD.

PMID- 22614906
TI  - Autoimmunity: SLE autoantibodies have lethal neurotoxic effects in female
      foetuses.

PMID- 22614908
TI  - Stem cells: Boosted bone healing in the MSC matrix.

PMID- 22614907
TI  - Meniscus pathology, osteoarthritis and the treatment controversy.
AB  - The menisci are internal structures that are of central importance for a healthy
      knee joint; they have a key role in the structural progression of knee
      osteoarthritis (OA), and the risk of the disease dramatically increases if they
      are damaged by injury or degenerative processes. Meniscus damage might be
      considered a signifying feature of incipient OA in middle-aged and elderly
      people. As approximately every third knee of people in these groups has a damaged
      meniscus, tears are common incidental findings of knee MRI. However, as most
      tears do not cause symptoms, careful clinical evaluation is required to determine
      if a damaged meniscus is likely to directly impact a patient's symptoms.
      Conservative management of patients with knee pain and a degenerative meniscal
      tear should be considered as a first-line therapy before surgical treatment is
      contemplated. Patients with mechanical interference of joint movements, such as
      painful catching or locking, might need surgical treatment with meniscal repair
      if possible. In a subset of patients, meniscal resection might relieve pain and
      other symptoms that potentially originate directly from the torn meniscus.
      However, the possibility of an increased risk of OA if functional meniscal tissue
      is removed cannot be overlooked.

PMID- 22614909
TI  - Neural strategies for selective attention distinguish fast-action video game
      players.
AB  - We investigated the psychophysical and neurophysiological differences between
      fast-action video game players (specifically first person shooter players, FPS)
      and non-action players (role-playing game players, RPG) in a visual search task.
      We measured both successful detections (hit rates) and steady-state visually
      evoked EEG potentials (SSVEPs). Search difficulty was varied along two
      dimensions: number of adjacent attended and ignored regions (1, 2 and 4), and
      presentation rate of novel search arrays (3, 8.6 and 20 Hz). Hit rates decreased
      with increasing presentation rates and number of regions, with the FPS players
      performing on average better than the RPG players. The largest differences in hit
      rate, between groups, occurred when four regions were simultaneously attended. We
      computed signal-to-noise ratio (SNR) of SSVEPs and used partial least squares
      regression to model hit rates, SNRs and their relationship at 3 Hz and 8.6 Hz.
      The following are the most significant results: RPG players' parietal responses
      to the attended 8.6 Hz flicker were predictive of hit rate and were positively
      correlated with it, indicating attentional signal enhancement. FPS players'
      parietal responses to the ignored 3 Hz flicker were predictive of hit rate and
      were positively correlated with it, indicating distractor suppression. Consistent
      with these parietal responses, RPG players' frontal responses to the attended 8.6
      Hz flicker, increased as task difficulty increased with number of regions; FPS
      players' frontal responses to the ignored 3 Hz flicker increased with number of
      regions. Thus the FPS players appear to employ an active suppression mechanism to
      deploy selective attention simultaneously to multiple interleaved regions, while
      RPG primarily use signal enhancement. These results suggest that fast-action
      gaming can affect neural strategies and the corresponding networks underlying
      attention, presumably by training mechanisms of distractor suppression.

PMID- 22614912
TI  - Efficacy and safety of first-line erlotinib in elderly patients with advanced non
      small cell lung cancer.
AB  - TaRceva LUng cancer Survival Treatment (TRUST) was an open-label, phase IV study
      of advanced non-small cell lung cancer (NSCLC). Patients failing or unsuitable
      for chemotherapy or radiotherapy received erlotinib 150 mg/day until progression.
      We examined a subpopulation of elderly patients (>=70 years) receiving first-line
      erlotinib (n=485) in TRUST. In this subpopulation, disease control rate (n=356
      with best response data available) was 79% (vs. 69% for the overall TRUST
      population; p<0.0001); median progression-free survival (PFS) was 4.57 months
      [95% confidence interval (CI), 3.68-5.22]; median overall survival (OS) was 7.29
      months (95% CI, 6.27-8.67); and one-year survival, was 36.6%. PFS and OS were
      significantly longer in patients developing rash, compared to those without, and
      in those with good performance status (PS; 0/1), compared to poor PS (>=2).
      Eighty-seven subpopulation patients (18%) had an erlotinib-related AE; other than
      the protocol-defined frequent adverse events (AEs); 4% had a grade >=3 erlotinib
      related AE, 7% had an erlotinib-related serious AE. In the subpopulation, dose
      reductions were required in 27%, most (97%) were reductions to 100 mg/day;
      treatment was discontinued in 10%, and one death was associated with treatment
      related toxicity (<1%). Erlotinib was effective and well-tolerated and may be
      considered for elderly patients with advanced NSCLC who are unsuitable for
      standard first-line chemotherapy or radiotherapy.

PMID- 22614911
TI  - Visual status and ocular morbidity in older adults living in residential care.
AB  - BACKGROUND: The frequency of visual impairment and blindness increases with age
      and is more prevalent among older adults living in residential care centers. The
      main aim of this study was to assess the visual status and determine the
      prevalence and major causes of visual impairment and blindness among the older
      adults living in residential care centers of Kathmandu Valley, Nepal. METHODS: A
      cross-sectional study was conducted on 385 residents of 60 years or older
      residing in seven residential care centers of Kathmandu Valley. Presenting
      distance visual acuity was assessed in each eye with a Snellen chart at 6-m
      distance in non-standardized outdoor illumination. Objective and subjective
      refractions were performed and the best-corrected distance visual acuity was
      considered in the better eye. Near acuity was assessed binocularly with The
      Lighthouse Near Acuity Card. Complete anterior and posterior segment examination
      was carried out. RESULTS: The mean age of residents was 74.34 +/- 8.19 years. The
      majority was female residents (78.2 %). The prevalence of visual impairment and
      blindness was 43.70 %. Adequate refractive correction could alone reduce the
      prevalence of visual impairment and blindness by 15.40 %. Cataract was the
      leading cause of visual impairment and blindness, which was followed by age
      related macular degeneration, corneal opacity, glaucoma, and macular scar.
      CONCLUSIONS: The prevalence of visual impairment and blindness is significant
      among the older adults living in residential care centers. The frequency of
      visual impairment and blindness can be prevented by adequate refractive
      correction, frequent eye examination, and appropriate high use of cataract
      surgery.

PMID- 22614910
TI  - Formation of immune complexes and thrombotic microangiopathy after intravitreal
      injection of bevacizumab in the primate eye.
AB  - BACKGROUND: In this study, the effect of intravitreal injection of bevacizumab on
      choroidal blood vessels was examined in primate eyes. METHODS: Four Cynomolgus
      monkeys received an intravitreal injection of 1.25 mg bevacizumab. The eyes were
      enucleated on days 1, 4, 7 and 14. For each animal, one eye was embedded in
      paraffin whereas the other eye was embedded for electron microscopy. Seven
      untreated or PBS (phosphate buffered saline)-injected monkeys were used as
      controls. RESULTS: Thrombotic microangiopathy was found in the choriocapillaris
      and choroidal vessels of all eight injected eyes. Acute microangiopathy was
      characterized ultrastructurally as swelling of the endothelium, loss of
      fenestrations and complete collapse of the capillaries, and was commonly observed
      in bevacizumab-treated eyes. Quantitative analysis showed reduction of the lumina
      of the choriocapillaris in the eyes of three of the monkeys. Bevacizumab was
      frequently localized inside the blood vessels, often filling the entire breadth
      of the vessels, and formed clusters with blood cells. Death of photoreceptors
      occurred in two monkeys. CONCLUSIONS: This study indicate that intravitreal
      injection of bevacizumab in monkeys induces activation of platelets,
      degranulation of thrombocytes and neutrophils, formation of immune complexes,
      thrombotic microangiopathy and alteration of the blood flow in choroidal vessels.

PMID- 22614914
TI  - Effects of etoposide on the proliferation of hexaploid H1 (ES) cells.
AB  - Etoposide is a specific inhibitor of topoisomerase II, which is an enzyme that
      enables double-stranded DNA to pass through another double-stranded DNA.
      Topoisomerase II is a major constituent of chromosome scaffold, existing at
      appreciable amounts in cells. To examine the effects of etoposide on the cell
      cycle, hexaploid H1 (ES) cells (6H1 cells) were used with diploid H1 (ES) cells
      (2H1 cells) as a control. Exponentially growing 2H1 and 6H1 cells were exposed to
      etoposide at various concentrations, and cultured for about 60 days in L15F10
      medium with leukemia inhibitory factor. With a high concentration of etoposide (1
      MUM), the DNA histograms showed G(2)/M accumulation, suggesting that etoposide
      arrested the cell cycle at the G(2)/M phase. With a low concentration of
      etoposide (50 nM), the cell proliferation was suppressed with a doubling time of
      98.4 h for 2H1 cells and 51.6 h for 6H1 cells, and without significant alteration
      in DNA histograms. Time-lapse videography revealed that 6H1 cells survived in the
      medium containing 50 nM etoposide had a cell cycle time of 18.8 h, which was
      equivalent to 19.2 h of the doubling time for the 6H1 cell population in drug
      free medium, suggesting that a part of the cell population died and was excluded
      from the cell system. It was concluded that etoposide affected the cell cycle at
      a wide range of concentrations.

PMID- 22614913
TI  - Mechanical loading with or without weight-bearing activity: influence on bone
      strength index in elite female adolescent athletes engaged in water polo,
      gymnastics, and track-and-field.
AB  - Bone health is considered not to benefit from water-based sports because of their
      weight-supported nature, but available evidence primarily relies on DXA
      technology. Our purpose was to investigate musculoskeletal health in the upper
      and lower body in well-trained adolescent female athletes using pQCT and compare
      these athletes with less-active, age- and sex-matched peers. Bone mineral
      content, volumetric cortical and trabecular BMD, total and cortical area, and
      bone strength index were assessed at the distal and proximal tibia and radius in
      four groups of adolescent females (mean age, 14.9 years) including water polo
      players (n = 30), gymnasts (n = 25), track-and-field athletes (n = 34), and
      nonactive controls (n = 28). Water polo players did not show any benefit in bone
      strength index or muscle size in the lower leg when compared with controls. In
      contrast, gymnasts showed 60.1 % and 53.4 % greater bone strength index at the
      distal and proximal tibia, respectively, than nonactive females (p < 0.05).
      Similarly, track-and-field athletes displayed 33.9 % and 14.7 % greater bone
      strength index at the distal and proximal tibia, respectively, compared with
      controls (p < 0.05). In the upper body, water polo players had 31.9 % greater
      bone strength index at the distal radius, but not the radial shaft, and 15.2 %
      larger forearm muscle cross-sectional area than controls (p < 0.05). The greatest
      musculoskeletal benefits in the upper body were found in gymnasts. In conclusion,
      despite training at an elite level, female water polo players did not show any
      benefits in musculoskeletal health in the lower leg and only limited benefits in
      the upper body when compared with nonactive girls.

PMID- 22614915
TI  - [Risk factors and prevention of youth suicide].

PMID- 22614916
TI  - Rap1GAP alters leukemia cell differentiation, apoptosis and invasion in vitro.
AB  - Rap1GAP which regulates the GTP-GDP form switch of Rap1 is a member of the GTPase
      activating protein (GAP) family and has recently received substantial attention.
      Rap1GAP is thought of as a putative tumor suppressor gene and plays an important
      role in human tumor progression including pancreatic cancer, thyroid cancer and
      melanoma. In the current study, we found that the expression of Rap1GAP was lower
      in acute myeloid leukemia (AML) patients compared to non-malignant blood disease
      patients. The expression of Rap1GAP was also low in HL-60, NB4, U937 and SHI-1
      myeloid leukemia cell lines. Upregulated Rap1GAP in NB4 and HL-60 cells promoted
      cell differentiation induced by ATRA or TPA compared to the empty vector control
      cells. Furthermore, Rap1GAP-transfected cells also showed a higher rate of
      apoptosis in response to arsenic trioxide compared to the control counterpart
      cells. In addition, we found that increased expression of Rap1GAP promoted
      leukemia cell invasion may be due to matrix metalloproteinase 9 (MMP9). In
      conclusion, these results demonstrated that Rap1GAP promoted leukemia cell
      differentiation and apoptosis, but increased leukemia cell invasion in vitro.

PMID- 22614918
TI  - Properties of a model aryl boronic acid and its boroxine.
AB  - Many boronic acid-containing molecules are currently under investigation as
      possible therapeutics. An increase in the knowledge of the physical and chemical
      properties of these compounds will lead to their improved formulation into usable
      dosage forms. The current study describes the formation and characterization of a
      boronic acid anhydride, called a boroxine. The model boronic acid, 4
      methoxybenzeneboronic acid is used. The current study demonstrates the utility of
      thermal (differential scanning calorimetry and thermogravimetric analysis) and
      spectral (solid-state nuclear magnetic resonance and ultraviolet spectroscopy)
      methods to quantitate and characterize the boronic acid and its boroxine,
      validated against definitive structures solved by single-crystal X-ray
      diffraction. The present work also demonstrates that the hydrolysis of the
      boroxine in the presence of water is very rapid in a time scale relative to drug
      substance manufacture and product formulation.

PMID- 22614917
TI  - ESI LC-MS and MS/MS characterization of antifungal cyclic lipopeptides produced
      by Bacillus subtilis XF-1.
AB  - Bacillus subtilis XF-1 (CGMCC No. 2357), a patent strain with good effects for
      controlling the clubroot of crucifer and many pathogenic fungi, was predicted to
      produce cyclic lipopeptide (CLP) antibiotics based on its genomic analysis. In
      this study, the CLPs were purified and determined with the following protocol:
      the supernatant of XF-1 cultivating mixture was firstly precipitated, then the
      precipitants were extracted with methanol and further separated by Sephadex LH-20
      chromatography to test its antifungal activities. Fungi-inhibiting fractions were
      further characterized with LC/ESI-MS and LC/ESI-MS/MS. The results show that four
      molecular ion peaks [M+H]+ (m/z 1,464, 1,478, 1,492 and 1,506) from fungi
      suppression fraction were identified as fengycin A with fatty acid of C16-C19,
      fengycin B (C14-C17), fengycin C (C15-C18), fengycin D (C15-C18) and fengycin S
      (C15-C18). Fengycin C (C15 and C18), fengycin D (C15, C16 and C18) and fengycin S
      (C15, C16 and C18) were reported for the first time. The diversity of the
      fengycins that exist in this strain will help the elucidation of their biocontrol
      mechanisms.

PMID- 22614919
TI  - Investigating the halochromic properties of azo dyes in an aqueous environment by
      using a combined experimental and theoretical approach.
AB  - The halochromism in solution of a prototypical example of an azo dye, ethyl
      orange, was investigated by using a combined theoretical and experimental
      approach. Experimental UV/Vis and Raman spectroscopy pointed towards a structural
      change of the azo dye with changing pH value (in the range pH 5-3). The pH
      sensitive behavior was modeled through a series of ab initio computations on the
      neutral and various singly and doubly protonated structures. For this purpose,
      contemporary DFT functionals (B3LYP, CAM-B3LYP, and M06) were used in combination
      with implicit modeling of the water solvent environment. Static calculations were
      successful in assigning the most-probable protonation site. However, to fully
      understand the origin of the main absorption peaks, a molecular dynamics
      simulation study in a water molecular environment was used in combination with
      time-dependent DFT (TD-DFT) calculations to deduce average UV/Vis spectra that
      take into account the flexibility of the dye and the explicit interactions with
      the surrounding water molecules. This procedure allowed us to achieve a
      remarkable agreement between the theoretical and experimental UV/Vis spectrum and
      enabled us to fully unravel the pH-sensitive behavior of ethyl orange in aqueous
      environment.

PMID- 22614920
TI  - Fluticasone furoate nasal spray reduces symptoms of  uncomplicated acute
      rhinosinusitis: a randomised  placebo-controlled study.
AB  - BACKGROUND: Uncomplicated acute rhinosinusitis (ARS) is usually a self-limiting
      inflammatory condition often treated with antibiotics. AIMS: To assess the safety
      and efficacy of fluticasone furoate nasal spray (FFNS) compared with placebo for
      symptomatic relief of uncomplicated ARS. METHODS: A randomised, double-blind,
      placebo-controlled, parallel-group, multicentre, 2-week treatment study of FFNS
      110 MUg once and twice daily was undertaken in adults/adolescents. RESULTS: A
      statistically significant reduction was seen in the daily major symptoms score, a
      composite score of three individual symptoms (nasal congestion/stuffiness, sinus
      headache/pressure or facial pain/pressure, and postnasal drip on a 0-3 scale) by
      both FFNS doses compared with placebo (least square mean differences vs. placebo
      of -0.386 (p=0.008) and -0.357 (p=0.014) for once daily and twice daily FFNS,
      respectively). The differences in median times to symptom improvement were not
      statistically significant between each dose of FFNS (7 days) and placebo (8
      days). There were no treatment differences in antibiotic use for possible
      fulminant bacterial rhinosinusitis (3% in each group). The safety profile of FFNS
      was similar to placebo. CONCLUSIONS: FFNS reduces symptoms of uncomplicated ARS
      compared with placebo and is well tolerated, providing support for withholding
      antibiotics in selected patients.

PMID- 22614921
TI  - Nestin protects mouse podocytes against high glucose-induced apoptosis by a Cdk5
      dependent mechanism.
AB  - Podocyte apoptosis contributes to the pathogenesis of diabetic nephropathy (DN).
      However, the mechanisms that mediate hyperglycemia-induced podocyte apoptosis
      remain poorly understood. Recent findings indicate that the disruption of the
      cytoskeleton is related to the podocyte apoptosis. In the present study, we
      investigated the involvement of nestin, an important cytoskeleton-associated
      class VI intermediate filament (IF) protein, in the high glucose (HG)-induced
      podocyte apoptosis. Our data showed that HG decreased the expression level of
      nestin, either mRNA or protein, in a time-dependent manner in cultured podocytes.
      Also, through knockdown of nestin expression by miRNA interference, the HG
      induced podocyte apoptotic rate was significantly increased. The expression of
      cleaved caspase-3 was also markedly elevated. Considering that nestin is a
      substrate of cyclin-dependent kinase 5 (Cdk5), we further assessed the expression
      of Cdk5 in HG-treated podocytes. The results showed that HG stimulation increased
      the protein and mRNA expression of Cdk5 in a time-dependent manner in cultured
      mouse podocytes. The protein activator of Cdk5, p35, was also increased in a time
      dependent manner by HG stimulation, and downregulation of Cdk5 by miRNA
      interference attenuated the nestin reduction in HG-treated podocytes; the HG
      induced podocyte apoptosis, the increased cleaved caspase-3 expression and the
      Bax/Bcl-2 ratio were all effectively attenuated. These data suggested that
      nestin, which is dependent on Cdk5 regulation, plays a cytoprotective role in HG
      induced podocyte apoptosis.

PMID- 22614922
TI  - Influence of age on arsenic-induced oxidative stress in rat.
AB  - Influence of age on arsenic-induced (0.05, 0.1, and 0.2 lethal dose to 50 %
      population (LD(50)) given intraperitoneally) oxidative stress was investigated in
      young, adult, and old rats at days 7 and 14 post-exposure. A significant dose
      dependent effect of arsenic on biochemical variables suggestive of oxidative
      stress was noted at day 7 following exposure in old rats. The parameters which
      were significantly altered include an increased reactive oxygen species,
      thiobarbituric acid reactive substances (TBARS), catalase activity accompanied by
      a decreased glutathione level. At day 14 following arsenic exposure (0.05 and 0.1
      LD(50) dose), we observed a significant oxidative injury as evident from
      significant depletion of superoxide dismutase (SOD) and catalase activities in
      blood and tissues in addition to more pronounced accumulation of arsenic in blood
      and tissues. Interestingly, the toxicity was pronounced in young and old rats
      compared with adult rats. Accumulation of arsenic found to be more prominent in
      old rats compared with young and adult, which might be due to impaired metabolism
      with ageing. We conclude that young and old animals are more vulnerable to the
      arsenic-induced oxidative injury which is comparable with arsenic accumulation in
      blood and tissues and duration of exposure.

PMID- 22614924
TI  - Time-dependent modulation of mitogen activated protein kinases and AKT in rat
      hippocampus and cortex in the pilocarpine model of epilepsy.
AB  - The epileptogenesis may involve a variety of signaling events that culminate with
      synaptic reorganization. Mitogen-activated protein kinases (MAPKs) and AKT may be
      activated by diverse stimulus including neurotransmitter, oxidative stress,
      growth factors and cytokines and are involved in synaptic plasticity in the
      hippocampus and cerebral cortex. The pilocarpine model in rodents reproduces the
      main features of mesial temporal lobe epilepsy related to hippocampus sclerosis
      (MTLE-HS) in humans. We analyze the phosphorylation profile of MAPKs (ERK1/2,
      p38(MAPK), JNK1/2/3) and AKT by western blotting in the hippocampus (Hip) and
      cortex (Ctx) of male adult wistar rats in different periods, after pilocarpine
      induced status epilepticus (Pilo-SE) and compared with control animals.
      Biochemical analysis were done in the Hip and Ctx at 1, 3, 12 h (acute period), 5
      days (latent period) and 50 days (chronic period) after Pilo-SE onset. Hence, the
      main findings include increased phosphorylation of ERK1 and p38(MAPK) in the Hip
      and Ctx 1 and 12 h after the Pilo-SE onset. The JNK2/3 isoform (54 kDa)
      phosphorylation was decreased at 3 h after the Pilo-SE onset and in the chronic
      period in the Hip and Ctx. The AKT phosphorylation increased only in the Hip
      during the latent period. Our study demonstrates, in a systematic manner, the
      profile of MAPKs and AKT modulation in the hippocampus and cerebral cortex in
      response to pilocarpine. Based in the role of each signaling enzyme is possible
      that these changes may be related, at least partially, to modifications in the
      intrinsic neuronal physiology and epileptogenic synaptic network that appears in
      the MTLE-HS.

PMID- 22614925
TI  - Neuron-astroglial interactions in cell-fate commitment and maturation in the
      central nervous system.
AB  - Neuron-astroglia interactions play a key role in several events of brain
      development, such as neuronal generation, migration, survival, and
      differentiation; axonal growth; and synapse formation and function. While there
      is compelling evidence of the effects of astrocyte factors on neurons, their
      effects on astrocytes have not been fully determined. In this review, we will
      focus on the role of neurons in astrocyte generation and maturation. Further, we
      highlight the great heterogeneity and diversity of astroglial and neural
      progenitors such as radial glia cells, and discuss the importance of the variety
      of cellular interactions in controlling the structural and functional
      organization of the brain. Finally, we present recent data on a new role of
      astrocytes in neuronal maturation, as mediators of the action of biolipids in the
      cerebral cortex. We will argue that the functional architecture of the brain
      depends on an intimate neuron-glia partnership, by briefly discussing the
      emerging view of how neuron-astrocyte dysfunctions might be associated with
      neurodegenerative diseases and neurological disorders.

PMID- 22614926
TI  - Neuroprotective effect of natural products against Alzheimer's disease.
AB  - Nature has gifted mankind with a plethora of flora-bearing fruits, vegetables and
      nuts. The diverse array of bioactive nutrients present in these natural products
      plays a pivotal role in prevention and cure of various neurodegenerative
      diseases, such as Alzheimer's disease (AD), Parkinson's disease and other
      neuronal dysfunctions. Accumulated evidence suggests that naturally occurring
      phyto-compounds, such as polyphenolic antioxidants found in fruits, vegetables,
      herbs and nuts, may potentially hinder neurodegeneration, and improve memory and
      cognitive function. Nuts such as walnut have also demonstrated neuroprotective
      effect against AD. The molecular mechanisms behind the curative effects rely
      mainly on the action of phytonutrients on distinct signalling pathways associated
      with protein folding and neuroinflammation. The neuroprotective effects of
      various naturally occurring compounds in AD is evaluating in this review.

PMID- 22614928
TI  - Selected region functionalized fungi with magnetic targeting properties and
      versatile purification capabilities.
AB  - A selected region functionalized strategy was proposed and realized here to
      combine the advantages of nanotechnology and living fungi activities.

PMID- 22614927
TI  - The role of astrocytic glycogen in supporting the energetics of neuronal
      activity.
AB  - Energy homeostasis in the brain is maintained by oxidative metabolism of glucose,
      primarily to fulfil the energy demand associated with ionic movements in neurons
      and astrocytes. In this contribution we review the experimental evidence that
      grounds a specific role of glycogen metabolism in supporting the functional
      energetic needs of astrocytes during the removal of extracellular potassium.
      Based on theoretical considerations, we further discuss the hypothesis that the
      mobilization of glycogen in astrocytes serves the purpose to enhance the
      availability of glucose for neuronal glycolytic and oxidative metabolism at the
      onset of stimulation. Finally, we provide an evolutionary perspective for
      explaining the selection of glycogen as carbohydrate reserve in the energy
      sensing machinery of cell metabolism.

PMID- 22614932
TI  - Effects of brucine on bone metabolism in multiple myeloma.
AB  - The aim of this study was to explore the effects of brucine on bone metabolism in
      multiple myeloma (MM) and to compare brucine and bortezomib regarding the effects
      on MM in vitro. The half maximal inhibitory concentration (IC50) values of
      brucine and bortezomib in the MM cell line U266 were detected by MTT assay. In
      addition, the expression of alkaline phosphatase (ALP), osteocalcin (OC),
      osteoprotegerin (OPG) and osteoprotegerin ligand (also termed receptor activator
      of nuclear factor kappaB ligand) (RANKL) at mRNA levels were measured by RT-PCR.
      IC50 of bortezomib in the U266 cell line at 48 h was 22.4 nmol/l, and that of
      brucine was 0.16 nmol/l. Compared with osteoblasts incubated with MM cell
      supernatant alone, the mRNA levels of ALP, OC and OPG in osteoblasts co-treated
      with brucine and MM cell supernatant were higher (p<0.05), while the mRNA
      expression of RANKL was lower, and the ranges of the changes were all larger than
      those of the group treated with bortezomib (P<0.05). Brucine exerts effects on
      bone metabolism in multiple myeloma through the regulation of osteoclasts by
      osteoblasts.

PMID- 22614934
TI  - CD8-positive pityriasis lichenoides-like mycosis fungoides.

PMID- 22614936
TI  - Counseling and directly observed medication for primary care buprenorphine
      maintenance: a pilot study.
AB  - OBJECTIVES: Counseling and medication adherence can affect opioid agonist
      treatment outcomes. We investigated the impact of 2 counseling intensities and 2
      medication-dispensing methods in patients receiving buprenorphine in primary
      care. METHODS: In a 12-week trial, patients were assigned to physician management
      (PM) with weekly buprenorphine dispensing (n = 28) versus PM and directly
      observed, thrice-weekly buprenorphine (DOT) and cognitive-behavioral therapy
      (CBT) (PM+DOT/CBT; n = 27) based on therapist availability. Fifteen-minute PM
      visits were provided at entry, after induction, and then monthly. Cognitive
      behavioral therapy was weekly 45-minute sessions provided by trained therapists.
      RESULTS: Treatment groups differed on baseline characteristics of years of opioid
      use, history of detoxification from opioids, and opioid negative urines during
      induction. Analyses adjusting for baseline characteristics showed no significant
      differences between groups on retention or drug use based on self-report or
      urines. Patient satisfaction was high across conditions, indicating acceptability
      of CBT counseling with observed medication. The number of CBT sessions attended
      was significantly associated with improved outcome, and session attendance was
      associated with a greater abstinence the following week. CONCLUSIONS: Although
      the current findings were nonsignificant, DOT and individual CBT sessions were
      feasible and acceptable to patients. Additional research evaluating the
      independent effect of directly observed medication and CBT counseling is needed.

PMID- 22614935
TI  - Buprenorphine for human immunodeficiency virus/hepatitis C virus-coinfected
      patients: does it serve as a bridge to hepatitis C virus therapy?
AB  - OBJECTIVES: Buprenorphine is associated with enhanced human immunodeficiency
      virus (HIV) treatment outcomes including increased antiretroviral therapy
      initiation rates, adherence, and CD4 cell counts among HIV-infected opioid
      dependent individuals. Buprenorphine facilitates hepatitis C virus (HCV)
      treatment in opioid-dependent patients with HCV monoinfection. Less is known
      about buprenorphine's role in HIV/HCV coinfection. METHODS: We conducted a
      retrospective chart review to evaluate HCV care for HIV-infected buprenorphine
      patients in the first 4 years of buprenorphine's integration into a Rhode Island
      HIV clinic. RESULTS: Sixty-one patients initiated buprenorphine. All had HCV
      antibody testing; 57 (93%) were antibody-positive. All antibody-positive patients
      underwent HCV RNA testing; 48 (84%) were RNA-positive. Of these, 15 (31%) were
      not referred to HCV care. Among chronically infected patients, 3 received HCV
      treatment after buprenorphine; all had cirrhosis and none achieved viral
      eradication. At buprenorphine induction, most patients had inadequately
      controlled HIV infection, with detectable HIV RNA (59%) or CD4 cell count less
      than or equal to 350/MUL (38%). CONCLUSIONS: Buprenorphine has shown limited
      success to date as a bridge to HCV treatment within an HIV clinic.
      Buprenorphine's stabilization of opioid dependence and HIV disease may permit the
      use of HCV therapy over time.

PMID- 22614937
TI  - Erectile dysfunction among male heroin addicts receiving methadone maintenance
      treatment in Guangdong, China.
AB  - OBJECTIVES: Erectile dysfunction (ED) is common among methadone-maintained
      patients and reduces their quality of life. This study reports the prevalence of
      ED among male heroin addicts receiving methadone maintenance treatment (MMT) in
      China and describes factors that may contribute to ED. METHODS: Seventy-four male
      heroin addicts enrolled in 4 MMT clinics for the first time were interviewed
      about general baseline characteristics. Scales for assessing erectile function
      and psychological disorders were completed monthly. Blood was drawn for serum
      hormone-level measurement at the baseline and at a 3-month follow-up. Daily
      methadone dosages were recorded by physicians. RESULTS: Erectile dysfunction was
      reported in 75.7%, 88.7%, 80.8%, and 80.9% of the patients at the baseline, 1-, 2
      , and 3-month follow-ups, respectively. No significant differences in the
      prevalence of ED were found during the course of treatment. About two-thirds of
      the patients who had ED at the 3-month follow-up had had the condition while on
      heroin. The delayed erectile function was significantly associated with duration
      of treatment (odd ratio, OR1-month vs baseline = 1.86, P = 0.021; OR2-month vs
      baseline = 1.67, P = 0.066) and methadone dosage (OR = 1.02, P = 0.038). Ongoing
      substance, serum hormone levels, and psychological disorders were not associated
      with ED. CONCLUSIONS: The prevalence of ED among male methadone-maintained
      patients in China is very high and individuals with altered erectile function
      while on heroin represent a high-risk group for the development of ED upon
      initiation of MMT. In the setting of delayed erectile function after receiving
      methadone, a trial of dosage reduction and symptomatic treatments may be a
      reasonable initial approach.

PMID- 22614938
TI  - Prevalence of ligamentum arteriosum calcification on multi-section spiral CT and
      digital radiography.
AB  - To investigate the prevalence of ligamentum arteriosum calcification (LAC) on
      multi-section spiral CT and digital radiography. Five hundred and eight children
      and 232 adults who performed multi-section chest CT were included in this study
      and were divided into nine age groups: A (0-5 years), B (6-10 years), C (11-15
      years), D (16-20 years), E (21-30 years), F (31-40 years), G (41-50 years), H (51
      60 years), and I (61-70 years). Two radiologists assessed the presence of LAC on
      axial and coronal CT images, defined as focal calcific density on both or on one
      plane with attenuation >100 Hounsfield unit. The prevalence of LAC on CT was
      compared between children and adults, and between unenhanced and enhanced CT in
      children. The prevalence of LAC on digital radiography was evaluated in 476
      children. The prevalence of definite LAC on unenhanced multi-section CT was
      significantly higher in children (37.8 %) than in adults (11.2 %) (P < 0.001),
      with prevalences in groups: A through I of 35.8, 48.7, 35.1, 28.6, 25.0, 10.2,
      15.5, 7.8, and 5.6 %, respectively. The prevalences of indeterminate LAC in age
      groups A-I on unenhanced multi-section CT were 4.5, 12.8, 8.1, 19.0, 0.0, 0.0,
      0.0, 2.0, and 1.9 %. In children, the prevalence of LAC was significantly higher
      on unenhanced than on enhanced CT (37.8 vs. 16.4 %, P < 0.001). The prevalence of
      LAC on digital radiography was 3.6 % in children. LAC is frequently observed in
      children and adults on multi-section spiral CT, more frequently than previously
      reported. Compared with that on multi-section spiral CT, the prevalence of LAC on
      digital radiography is substantially low.

PMID- 22614941
TI  - Congratulations to Professor Pavel Mach on the occasion of his 60th birthday.

PMID- 22614939
TI  - Influence of changing plant food sources on the gut microbiota of saltmarsh
      detritivores.
AB  - Changes in agricultural land-use of saltmarshes along the German North Sea coast
      have favoured the succession of the marsh grass Elytrigia atherica over the long
      established Spartina anglica. Consequently, E. atherica represents a potential
      food source of increasing importance for plant-feeding soil detritivores.
      Considering the importance of this ecological guild for decomposition processes
      and nutrient cycling, we focussed on two sympatric saltmarsh soil
      macrodetritivores and their associated gut microbiota to investigate how the
      digestive processes of these species may be affected by changing plant food
      sources. Using genetic fingerprints of partial 16S rRNA gene sequences, we
      analysed composition and diversity of the bacterial gut community in a diplopod
      and an amphipod crustacean in relation to different feeding regimes representing
      the natural vegetation changes. Effects of syntopy on the host-specific gut
      microbiota were also taken into account by feeding the two detritivore species
      either independently or on the same plant sample. Bacterial community composition
      was influenced by both the host species and the available plant food sources, but
      the latter had a stronger effect on microbial community structure. Furthermore,
      bacterial diversity was highest after feeding on a mixture of both plant species,
      regardless of the host species. The gut microbiota of these two detritivores can
      thus be expected to change along with the on-going succession at the plant
      community level in this environment. Cloning and sequencing of bacterial 16S rRNA
      gene fragments further indicated a host-related effect since the two detritivores
      differed in terms of predominant bacterial taxa: diplopods harboured mainly
      representatives of the phyla Bacteroidetes and Gammaproteobacteria. In contrast,
      the genus Vibrio was found for the amphipod host across all feeding conditions.

PMID- 22614942
TI  - A novel role for insulin resistance in the connection between obesity and
      postmenopausal breast cancer.
AB  - The past two decades have seen a drastic increase in obesity rates in Western
      societies and emerging countries. As such, it has become increasingly important
      to understand the molecular mechanisms by which obesity affects the risk of
      developing associated co-morbidities. The present study aimed at identifying the
      effect of insulin on breast cancer and breast epithelial cells, reflective of
      obesity-associated hyperinsulinaemia, as a molecular explanation for the
      increased risk of oestrogen receptor-negative postmenopausal breast cancer in
      obese women. Both of the examined breast cancer cell lines (MDA-MB-231 and SK-BR
      3) showed intact insulin signalling (insulin receptor phosphorylation and
      activation of phosphoinositol-3 kinase and mitogen-activated protein kinase cell
      signalling pathways), with MDA-MB-231 cells showing aberrantly amplified insulin
      signalling. Insulin did not induce a physiologically significant change in
      proliferation or apoptosis in either cell line. MDA-MB-231 cells showed decreased
      cell proliferation and increased S-phase population, while SK-BR-3 cells showed
      increased cyclin D and cyclin E gene expression and increased necrosis after
      insulin treatment. Hyperinsulinaemia may not be a universal mechanism by which
      obesity affects breast cancer progression. Normal breast epithelial cells (MCF
      10A) showed intact insulin signalling, increased cell proliferation and reduced
      apoptosis after insulin treatment, suggesting cell growth and survival-promoting
      effects of insulin on these cells. Thus, hyperinsulinaemia may affect breast
      cancer aetiology rather than progression and this finding may provide a novel
      molecular mechanism for the role of insulin in the promotion of increased
      postmenopausal breast cancer risk in obese women.

PMID- 22614940
TI  - An improved sequence-aided T-RFLP analysis of bacterial succession during oyster
      mushroom substrate preparation.
AB  - While oyster mushroom (Pleurotus spp.) is one of the most popular cultivated
      edible mushrooms, there is scanty information about the microbial community
      taking part in mushroom substrate production. In this study, an improved sequence
      aided terminal restriction fragment length polymorphism (T-RFLP) was used to
      identify and (semi-)quantify the dominant bacteria of oyster mushroom substrate
      preparation. The main features of the improved T-RFLP data analysis were the
      alignment of chromatograms with variable clustering thresholds, the visualization
      of data matrix with principal component analysis ordination superimposed with
      cluster analysis, and the search for stage-specific peaks (bacterial taxa) with
      similarity percentage (analysis of similarity) analysis, followed by
      identification with clone libraries. By applying this method, the dominance of
      the following bacterial genera was revealed during oyster mushroom substrate
      preparation: Pseudomonas and Sphingomonas at startup, Bacillus, Geobacillus,
      Ureibacillus, Pseudoxanthomonas, and Thermobispora at the end of partial
      composting, and finally several genera of Actinobacteria, Thermus, Bacillus,
      Geobacillus, Thermobacillus, and Ureibacillus in the mature substrate. As the
      proportion of uncultured bacteria increased during the process, it is worth
      establishing strain collections from partial composting and from mature substrate
      for searching new species.

PMID- 22614943
TI  - Obituary. Prof. Dr. Angelika Bierhaus.

PMID- 22614945
TI  - Definition of an intramolecular Eu-to-Eu energy transfer within a discrete [Eu2L]
      complex in solution.
AB  - Ligand L, based on two do3a moieties linked by the methylene groups of 6,6'
      dimethyl-2,2'-bipyridine, was synthesized and characterized. The addition of Ln
      salts to an aqueous solution of L (0.01 M Tris-HCl, pH 7.4) led to the successive
      formation of [LnL] and [Ln(2)L] complexes, as evidenced by UV/Vis and
      fluorescence titration experiments. Homodinuclear [Ln(2)L] complexes (Ln = Eu,
      Gd, Tb, Yb, and Lu) were prepared and characterized. The (1)H and (13)C NMR
      spectra of the Lu and Yb complexes in D(2)O solution (pD = 7.0) showed C(1)
      symmetry of these species in solution, pointing to two different chemical
      environments for the two lanthanide cations. The analysis of the chemical shifts
      of the Yb complex indicated that the two coordination sites present square
      antiprismatic (SAP) coordination environments around the metal ions. The
      spectroscopic properties of the [Tb(2)L] complex upon ligand excitation revealed
      conventional behavior with tau(H2O) = 2.05(1) ms and phi(H2O) = 51%, except for
      the calculation of the hydration number obtained from the luminescent lifetimes
      in H(2)O and D(2)O, which pointed to a non-integer value of 0.6 water molecules
      per Tb(III) ion. In contrast, the Eu complex revealed surprising features such
      as: 1) the presence of two and up to five components in the (5)D(0)->(7)F(0) and
      (5)D(0)->(7)F(1) emission bands, respectively; 2) marked differences between the
      normalized spectra obtained in H(2)O and D(2)O solutions; and 3) unconventional
      temporal evolution of the luminescence intensity at certain wavelengths, the
      intensity profile first displaying a rising step before the occurrence of the
      expected decay. Additional spectroscopic experiments performed on [Gd(2-x)Eu(x)L]
      complexes (x = 0.1 and 1.9) confirmed the presence of two distinct Eu sites with
      hydration numbers of 0 (site I) and 2 (site II), and showed that the
      unconventional temporal evolution of the emission intensity is the result of an
      unprecedented intramolecular Eu-to-Eu energy-transfer process. A mathematical
      model was developed to interpret the experimental data, leading to energy
      transfer rates of 0.98 ms(-1) for the transfer from the site with q=0 to that
      with q=2 and vice versa. Hartree-Fock (HF) and density functional theory (DFT)
      calculations performed at the B3LYP level were used to investigate the
      conformation of the complex in solution, and to estimate the intermetallic
      distance, which provided Forster radii (R(0)) values of 8.1 A for the energy
      transfer from site I to site II, and 6.8 A for the reverse energy transfer. These
      results represent the first evidence of an intramolecular energy-transfer
      equilibrium between two identical lanthanide cations within a discrete molecular
      complex in solution.

PMID- 22614944
TI  - Predictive value of the MGMT promoter methylation status in metastatic melanoma
      patients receiving first-line temozolomide plus bevacizumab in the trial SAKK
      50/07.
AB  - The O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status is
      a predictive parameter for the response of malignant gliomas to alkylating agents
      such as temozolomide. First clinical trials with temozolomide plus bevacizumab
      therapy in metastatic melanoma patients are ongoing, although the predictive
      value of the MGMT promoter methylation status in this setting remains unclear. We
      assessed MGMT promoter methylation in formalin-fixed, primary tumor tissue of
      metastatic melanoma patients treated with first-line temozolomide and bevacizumab
      from the trial SAKK 50/07 by methylation-specific polymerase chain reaction. In
      addition, the MGMT expression levels were also analyzed by MGMT
      immunohistochemistry. Eleven of 42 primary melanomas (26%) revealed a methylated
      MGMT promoter. Promoter methylation was significantly associated with response
      rates CR + PR versus SD + PD according to RECIST (response evaluation criteria in
      solid tumors) (p<0.05) with a trend to prolonged median progression-free survival
      (8.1 versus 3.4 months, p>0.05). Immunohistochemically different protein
      expression patterns with heterogeneous and homogeneous nuclear MGMT expression
      were identified. Negative MGMT expression levels were associated with overall
      disease stabilization CR+PR+SD versus PD (p=0.05). There was only a poor
      correlation between MGMT methylation and lack of MGMT expression. A significant
      proportion of melanomas have a methylated MGMT promoter. The MGMT promoter
      methylation status may be a promising predictive marker for temozolomide therapy
      in metastatic melanoma patients. Larger sample sizes may help to validate
      significant differences in survival type endpoints.

PMID- 22614946
TI  - Novel phosphorescent hydrogels based on an Ir(III) metal complex.
AB  - Novel phosphorescent hydrogels have been explored by immobilizing an Ir(III)
      metal complex into the matrices of hydrogels. FTIR spectra demonstrate that the
      Ir(III) -PNaAMPS hydrogel is achieved by irreversible incorporation of positively
      charged [Ir(ppy)(2)(dmbpy)]Cl (ppy = 2-phenylpyrine, dmbpy = 4,4'-dimethyl-2,2'
      bipyridine) into negatively charged poly(2-acrylamido-2-methylpropane sulfonic
      acid sodium) (PNaAMPS) hydrogel via electrostatic interaction. The
      photoluminescent spectra indicate that the Ir(III)-PNaAMPS hydrogel exhibits
      stable phosphorescence. In vitro cultivation of human retinal pigment epithelial
      cells demonstrates the cytocompatibility of the Ir(III)-PNaAMPS hydrogel. This
      work herein represents a facile pathway for fabrication of phosphorescent
      hydrogels.

PMID- 22614947
TI  - Dimerization determines substrate specificity of a bacterial prenyltransferase.
AB  - We have identified the native dimer interface of heptaprenylglyceryl phosphate
      synthase PcrB from the bacterium Bacillus subtilis and analyzed the significance
      of oligomer formation for stability and catalytic activity. Computational methods
      predicted two different surface regions of the PcrB protomer that could be
      responsible for dimer formation. These bona fide interfaces were assessed both in
      silico and experimentally by the introduction of amino acid substitutions that
      led to monomerization, and by incorporation of an unnatural amino acid to allow
      cross-linking of the two protomers. The results showed that, in contrast to
      previous assumptions, PcrB uses the same interface for dimerization as the
      homologous geranylgeranylglyceryl phosphate synthase from Archaea. Thermal
      unfolding demonstrated that the monomeric proteins are only slightly less stable
      than wild-type PcrB. However, activity assays showed that monomerization limits
      the length of accepted polyprenyl pyrophosphates to three isoprene units, whereas
      the native PcrB substrate contains seven isoprene entities. We provide a
      plausible hypothesis as to how dimerization determines substrate specificity of
      PcrB.

PMID- 22614948
TI  - Unravelling the genetic bases of non-target-site-based resistance (NTSR) to
      herbicides: a major challenge for weed science in the forthcoming decade.
AB  - Non-target-site-based resistance (NTSR) can confer unpredictable cross-resistance
      to herbicides. However, the genetic determinants of NTSR remain poorly known. The
      current, urgent challenge for weed scientists is thus to elucidate the bases of
      NTSR so that detection tools are developed, the evolution of NTSR is understood,
      the efficacy of the shrinking herbicide portfolio is maintained and integrated
      weed management strategies, including fully effective herbicide applications, are
      designed and implemented. In this paper, the importance of NTSR in resistance to
      herbicides is underlined. The most likely way in which NTSR evolves-by
      accumulation of different mechanisms within individual plants-is described. The
      NTSR mechanisms, which can interfere with herbicide penetration, translocation
      and accumulation at the target site, and/or protect the plant against the
      consequences of herbicide action, are then reviewed. NTSR is a part of the plant
      stress response. As such, NTSR is a dynamic process unrolling over time that
      involves 'protectors' directly interfering with herbicide action, and also
      regulators controlling 'protector' expression. NTSR is thus a quantitative trait.
      On this basis, a three-step procedure is proposed, based on the use of the
      'omics' (genomics, transcriptomics, proteomics or metabolomics), to unravel the
      genetic bases of NTSR.

PMID- 22614949
TI  - Variability in the position of the retropharyngeal internal carotid artery.
AB  - The retropharyngeal internal carotid artery (ICA) is a well-described arterial
      anomaly with important implications for patients undergoing pharyngeal approach
      surgical procedures. Existing clinical and imaging classification schemes for a
      retropharyngeal ICA take into account arterial distance to the pharyngeal mucosal
      wall. We describe a case of mobility of a retropharyngeal ICA between short
      interval imaging studies. The possibility of respiratory variability or other
      etiologies causing such changes in retropharyngeal carotid position have not been
      described previously. Our findings suggest that imaging findings from a single
      study alone may not be sufficient to confidently exclude this clinically
      significant arterial anomaly.

PMID- 22614950
TI  - Alcohol induces Golgi fragmentation in differentiated PC12 cells by deregulating
      Rab1-dependent ER-to-Golgi transport.
AB  - In the present study, we analyze the effects of ethanol on the Golgi structure
      and membrane transport in differentiated PC12 cells, which are used as a model of
      neurons. Chronic exposure to moderate doses of ethanol induces Golgi
      fragmentation, a common characteristic of many neurodegenerative diseases.
      Alcohol impaired the lateral linking of stacks without causing microtubule
      damage. Extensive immunocytochemical and western blot analyses of representative
      Golgi proteins showed that few, but important, proteins are significantly
      affected. Thus, alcohol exposure induced a significant ER-to-Golgi transport
      delay, the retention of the GTPase Rab1 in the Golgi membranes and the
      accumulation of tethering factor p115 in the cytosol. These modifications would
      explain the observed fragmentation. The amount of p115 and the stacking protein
      GRASP65 increased in alcohol-treated cells, which might be a mechanism to reverse
      Golgi damage. Importantly, the overexpression of GTP-tagged Rab1 but not of a
      dominant-negative Rab1 mutant, restored the Golgi morphology, suggesting that
      this protein is the main target of alcohol. Taken together, our results support
      the view that alcohol and neurodegenerative diseases such as Parkinson have
      similar effects on intracellular trafficking and provide new clues on the
      neuropathology of alcoholism.

PMID- 22614953
TI  - 1.9 Mb microdeletion of 21q22.11 within Braddock-Carey contiguous gene deletion
      syndrome region: dissecting the phenotype.
AB  - Braddock-Carey syndrome is characterized by Pierre Robin sequence, agenesis of
      the corpus callosum, facial dysmorphisms, developmental delay, and congenital
      thrombocytopenia. Recently, Braddock-Carey syndrome was demonstrated to be caused
      by chromosomal microdeletion in 21q22 including the RUNX1 gene, whose
      haploinsufficiency is responsible for thrombocytopenia phenotype. Therefore, the
      syndrome has emerged as a contiguous gene deletion syndrome. Here, we describe an
      infant with Pierre Robin sequence, facial anomalies, congenital heart defects,
      hypotonia, and the absence of thrombocytopenia, who was found to have a 1.9 Mb
      microdeletion within the Braddock-Carey contiguous deletion syndrome region. This
      deletion spares the RUNX1 gene, narrowing the genomic region responsible for a
      part of the Braddock-Carey syndrome phenotype. Further studies are awaited to
      understand the role of the genes located within 21q22 in the pathogenesis of
      Braddock-Carey syndrome.

PMID- 22614952
TI  - Probing the N-terminal sequence of spinach PsbO: evidence that essential
      threonine residues bind to different functional sites in eukaryotic photosystem
      II.
AB  - The N-terminal 1E-6L domain of the manganese-stabilizing protein (PsbO) from
      spinach prevents non-specific binding of the subunit to photosystem II (PSII) and
      deletions of the 1E-7T or 1E-15T sequences from the PsbO N-terminus reduce or
      impair, respectively, functional binding of PsbO to PSII (Popelkova et al.,
      Biochemistry 42:6193-6200, 2003). The work presented here provides deeper
      insights into the interaction of PsbO with PSII. The data show that a single
      mutation, 15T -> A in mature PsbO from spinach reduces the stoichiometry of its
      functional binding from two to one subunit per PSII and decreases reconstitution
      of activity to about 45 % of the wild-type control. Replacement of the 1E-6L
      domain with 6M in the T15A PsbO mutant has no additional negative effect on
      recovery of O2 evolution activity, but it significantly weakens both functional
      and nonspecific binding of the truncated mutant to PSII. These results suggest
      that the 15T side-chain by itself is essential for binding of one of two PsbO
      subunits to eukaryotic PSII and that specific PSII-binding sites for PsbO are
      distinguishable; one PSII-binding site does not require PsbO-15T and probably
      interacts with the other N-terminal domain of PsbO. Identity of the latter domain
      is revealed by a requirement for the presence of the 1E-6L sequence that is shown
      here to be necessary for high-affinity binding of PsbO to PSII. When combined
      with previous results, the data presented here lead to a more detailed model for
      PsbO binding in eukaryotic PSII.

PMID- 22614954
TI  - Different neuroprotection and therapeutic time windows by two specific diazepam
      regimens on retinal ganglion cells after optic nerve transection in adult rats.
AB  - PURPOSE: To compare neuroprotection and therapeutic time windows of two diazepam
      regimens on retinal ganglion cells (RGCs) after rat optic nerve transection
      (ONT). METHODS: Adult rats received initial intraperitoneal diazepam injections
      30 minutes before left ONT, followed by daily diazepam (regimen-A) or every 8
      hours for 3 days (regimen-B) until they were killed at day 7 or 14. Initial
      diazepam in regimen-A and regimen-B was delayed to 3, 6, 7, 9, 10, 12 and 6, 7,
      8, 9, 10, 12 hours after ONT and these animals survived for 7 days. The effect of
      daily combinational uses of diazepam and bicuculline was assayed at 7 days.
      RESULTS: Regimen-A induced higher RGC densities than those in control and regimen
      B groups at day 7, but lower density than regimen-B did at day 14. When initial
      diazepam was delayed beyond 6 or 8 hours after ONT with regimen-A and regimen-B,
      the promoting effects of diazepam on RGC densities disappeared. Bicuculline
      completely inhibited the protection of diazepam. CONCLUSIONS: Prolonged
      neuroprotection on RGCs at day 14 and extended therapeutic time window for 8
      hours can be achieved by regimen-B, while regimen-A induces a stronger
      neuroprotection at day 7. Diazepam neuroprotection is mediated through GABAA
      receptor.

PMID- 22614955
TI  - Transient focal cerebral ischemia upregulates immunoproteasomal subunits.
AB  - This study was designed to determine whether focal cerebral ischemia alters the
      expression of the immunoproteasomal (i-proteasomal) subunits. Transient cerebral
      ischemia significantly increased the expression of the i-proteasomal subunits,
      20S beta1i (LMP2) and beta5i (LMP7) in the parietal cortex and hippocampus. This
      alteration was associated with a remarkable increase in ubiquitinated proteins.
      It is likely that the postischemic induction of the i-proteasome plays an
      important role in coping with the damaged proteins and thus may have an important
      effect on neuronal survival and death.

PMID- 22614957
TI  - Increased NRF2 gene (NFE2L2) copy number correlates with mutations in lung
      squamous cell carcinomas.
AB  - Nuclear factor (erythroid-derived 2)-like 2 (NRF2) is a transcription factor
      belonging to the cap 'n' collar subfamily of the basic-leucine zipper (bZIP)
      family of transcription factors, which plays a significant role in adaptive
      responses to oxidative stress. Previously, we reported that NRF2 gene (NFE2L2)
      mutations correlate with poor prognosis of lung squamous cell carcinomas. We
      therefore hypothesized that an increased NRF2 gene copy number may correlate with
      clinicopathological features in lung cancer patients. In this study, the
      increased copy number of the NRF2 gene was analyzed by real-time polymerase chain
      reaction (real-time-PCR) amplifications in 90 surgically-treated non-small cell
      lung cancer (NSCLC) cases. In total, 16 NRF2 mutation cases were included. An
      increased NRF2 gene copy number was found in 7 (7.8%) lung squamous cell
      carcinoma patients. Increased NRF2 copy number status significantly correlated
      with mutation status (mutant, 31.25% vs. wild-type, 2.7%; p=0.0017). The mean
      NRF2 gene copy number was significantly higher in mutant (2.478 +/- 0.668)
      compared to wild-type NRF2 (1.917 +/- 0.737) (p=0.0048). However, the copy number
      did not correlate with smoking status (p=0.3741), gender (p=0.1545), age (>=65
      vs. <65, p=0.1237) and pathological stage. Although an increased NRF2 copy number
      correlates with mutations in squamous cell carcinoma, the percentage of the
      increased copy number was low; therefore, another mechanism may exist for the
      activation of NRF2 mutations in cancer.

PMID- 22614958
TI  - Lung cancer screening: examining the issues.
AB  - The goal of screening is to detect disease at a stage when cure or control is
      possible, thereby decreasing disease-specific deaths in the population. Many
      studies have attempted to demonstrate that lung cancer screening using chest
      radiography or computed tomography (CT) identifies patients with lung cancer and
      reduces cancer-related mortality. Until recently, there was no evidence
      confirming a reduction in disease-specific mortality with screening. Early cancer
      screening should result in a gradual population-wide stage shift toward earlier
      cancer stages over time, but stage shifting was not reported in early lung cancer
      screening studies. Lead-time, length-time, and overdiagnosis biases may each have
      an impact on screening studies reporting survival as an outcome. In this past
      year, the National Lung Screening Trial reported a significant reduction in
      cancer-related mortality as a result of screening with chest CT imaging. This
      will shape the direction of future screening programs.

PMID- 22614959
TI  - Bronchoscopy and endobronchial ultrasound for diagnosis and staging of lung
      cancer.
AB  - Various techniques, including standard bronchoscopy, transthoracic needle
      aspiration and mediastinoscopy, are used for diagnosis and staging of lung
      cancer. Minimizing the number of invasive procedures for lung cancer diagnosis
      and staging is preferred, however, and a growing number of bronchoscopic
      techniques are being used. Currently available techniques for the initial
      diagnosis of lung cancer include electromagnetic navigation bronchoscopy with
      computed tomography mapping and sample collection, endobronchial ultrasound
      (EBUS) using radial or convex probe tips, and the combination of the two
      approaches. EBUS with transbronchial needle aspiration (EBUS-TBNA) is highly
      specific and sensitive for the examination of mediastinal lymph nodes. Several
      studies have demonstrated the utility of this approach for less invasive lung
      cancer mediastinal staging. EBUS-TBNA has also been used in the collection of
      tissue samples for the analysis of tumor biomarkers that significantly influence
      the selection of cancer treatment strategies. Evidence suggests that EBUS-TBNA
      may be less useful for restaging patients with lung cancer after cytotoxic
      therapy.

PMID- 22614960
TI  - Preoperative evaluation of the lung resection candidate.
AB  - Lung resection provides the greatest likelihood of cure for patients with
      localized lung cancer, but is associated with a risk of mortality, decreased
      postoperative lung function, and other complications. Lung function testing using
      spirometry, diffusing capacity of the lung for carbon monoxide, and peak oxygen
      consumption helps predict the risk of postoperative complications including
      mortality. Predicting postoperative lung function using the proportion of lung
      segments to be resected, radionuclide scanning, or other methods is important for
      assessing surgical risk. The American College of Chest Physicians, the European
      Respiratory Society/European Society of Thoracic Surgeons and the British
      Thoracic Society guidelines provide detailed algorithms for preoperative risk
      assessment, but their recommended approaches differ somewhat. Smoking cessation
      and pulmonary rehabilitation are perioperative measures that can improve
      patients' the short- and long-term outcomes.

PMID- 22614961
TI  - Video-assisted thoracoscopic surgery for the treatment of lung cancer.
AB  - A growing proportion of lung resections is being performed by video-assisted
      thoracoscopic surgery (VATS). VATS lobectomy is indicated for clinical stage I
      suspected lung cancer with pulmonary function sufficient to tolerate resection.
      Retrospective and matched analyses suggest less morbidity with fewer
      postoperative complications with VATS compared with open lobectomy. Five-year
      survival for VATS lobectomy in stage I non-small lung cancer patients approaches
      80%. A potential oncologic benefit of VATS lobectomy (over thoracotomy) has been
      proposed through attenuation of postoperative cytokine release. Regardless of
      whether VATS or an open approach is utilized, thorough lymphadenectomy is
      important and may confer an additional survival benefit.

PMID- 22614962
TI  - Stereotactic body radiotherapy for stage I non-small cell lung cancer.
AB  - Surgical resection for patients with stage I non-small cell lung cancer (NSCLC)
      produces high long-term survival rates, but many patients are ineligible for
      surgery because of medical comorbidity or other factors. Stereotactic body
      radiotherapy (SBRT) is the standard of care for patients with medically
      inoperable stage I NSCLC. Studies have reported local control rates with SBRT of
      about 95% when an adequate radiation dose is used. Lymph node failure averages
      less than 5%, while distant metastatic recurrence represents the most common site
      of failure. SBRT is generally safe and well tolerated even by patients with
      substantial pulmonary comorbidities. On average, lung function tests reveal
      little or no change from baseline, although individual patients may exhibit
      changes in pulmonary function after treatment. Most studies report pneumonitis
      rates of 0% to 5%. Ongoing clinical trials are investigating single-fraction SBRT
      and evaluating the maximal tolerated dose for centrally located tumors.

PMID- 22614963
TI  - Locally advanced non-small cell lung cancer: what is the optimal concurrent
      chemoradiation regimen?
AB  - The optimal chemoradiation regimen for patients with locally advanced non-small
      cell lung cancer (NSCLC) has yet to be defined. Disease and patient heterogeneity
      prevent a "one size fits all" approach to treatment. Concurrent chemoradiation up
      front is the definitive strategy for patients with unresectable stage III NSCLC;
      the addition of consolidation chemotherapy following definitive treatment has
      produced conflicting results with respect to overall survival. Biologic therapies
      have yet to show value as add-on treatment to chemoradiation.

PMID- 22614964
TI  - The role of surgery for locally advanced non-small cell lung cancer.
AB  - Accurate clinical staging of patients with locally advanced non -small cell lung
      cancer (NSCLC) is critical in identifying surgical candidates, who are typically
      patients with stage N2 disease. Preoperative staging by 18(F)-fluorodeoxyglucose
      positron emission tomography can alter staging and therefore influence the
      selection of therapy. The staging evaluation should include an assessment of the
      mediastinal lymph nodes; mediastinal lymph node involvement is a negative
      prognostic indicator. When the treatment plan potentially includes surgery,
      multidisciplinary evaluation including physiologic evaluation is essential, as
      surgery is aggressive with potential morbidity. Multimodality therapy offers the
      best chance for improved progression-free and overall survival. Patients with
      potentially resectable NSCLC who are downstaged following induction chemotherapy
      have a superior prognosis compared with those whose stage is unaltered.

PMID- 22614965
TI  - The role of adjuvant chemotherapy in early-stage and locally advanced non-small
      cell lung cancer.
AB  - Adjuvant chemotherapy benefits only a small proportion of patients in the setting
      of resected early-stage non-small cell lung cancer, and in unselected patients,
      any benefit is modest. Analysis of clinical trials of adjuvant chemotherapy
      revealed that differential expression of DNA repair proteins and a 15-gene
      expression profile affected outcomes with treatment. Biomarkers and gene
      expression profiles are now being studied in prospective clinical trials to gauge
      their value in selection of adjuvant therapy and individualization of therapy.

PMID- 22614966
TI  - Selection of chemotherapy for patients with advanced non-small cell lung cancer.
AB  - Chemotherapy remains the first-line treatment for most patients with stage IV non
      small cell lung cancer (NSCLC), but optimal regimens are now defined by
      histology. Platinum-based regimens with pemetrexed, bevacizumab, or both are
      reasonable first-line options for patients with nonsquamous NSCLC. The standard
      treatment for squamous NSCLC remains a platinum doublet with a drug other than
      pemetrexed. Maintenance therapy is emerging as a treatment strategy for patients
      who do not progress after four cycles of first-line chemotherapy. In the
      maintenance setting, pemetrexed and erlotinib significantly prolong overall
      survival compared with placebo after the completion of first-line chemotherapy.

PMID- 22614967
TI  - The emerging role of palliative medicine in the treatment of lung cancer
      patients.
AB  - The symptom burden of patients with lung cancer is extensive and includes loss of
      appetite, dyspnea, and other symptoms that lead to decreased quality of life.
      Randomized controlled trial data indicate that early palliative care improves
      quality of life and depressive symptoms and may extend survival in advanced non
      small cell lung cancer compared with standard care. Combining an appetite
      stimulant (megestrol acetate) with an atypical antipsychotic (olanzapine) leads
      to greater weight gain and appetite improvement compared with an appetite
      stimulant alone. Cancer-related dyspnea appears to be a "central" effect that
      stems from altered afferent inputs in the setting of ventilatory muscle weakness;
      various treatment options that have shown success in treating cancer-related
      dyspnea are opioids, tunneled pleural catheters, bilevel positive airway
      pressure, and nebulized furosemide. Buprenorphine is a unique opioid with
      activity at mu and nociceptin receptors (also called opioid-receptor-like
      receptors); it improves pain states dominated by central sensitization.

PMID- 22614968
TI  - Personalized targeted therapy in advanced non-small cell lung cancer.
AB  - Personalized targeted therapy for advanced non-small cell lung cancer (NSCLC)
      primarily relies on the concept of "oncogene addiction," in which multiple
      genetic abnormalities are addicted to one or a few genes for tumor cell
      maintenance and survival. Several molecular aberrations have been identified in
      NSCLC, with subsequent development of drugs targeted to these aberrations;
      gefitinib, erlotinib, and cetuximab for the treatment of NSCLC harboring
      epidermal growth factor receptor mutation or overexpression, and crizotinib for
      the treatment of NSCLC with the EML4-ALK fusion translocation oncogene being some
      examples. A more recent actionable target is MET, a multifaceted receptor
      tyrosine kinase within the human kinome. Cellular heterogeneity within an
      oncogene-addicted tumor can cause resistance to targeted therapy after an initial
      response. As our understanding of tumor heterogeneity and tumor resistance
      mechanisms evolves, more rational therapies and combinations of therapies can be
      expected.

PMID- 22614969
TI  - Treatment implications of the new lung cancer staging system.
AB  - The American Joint Commission on Cancer along with the International Association
      for the Study of Lung Cancer (IASLC) has published new guidelines for lung cancer
      staging based on observations from 100,869 lung cancer patients. Revised tumor,
      node, metastasis (TNM) criteria were derived from IASLC patient survival curves,
      and were validated using data from the Surveillance, Epidemiology, and End Report
      program. The seventh edition TNM classification revised the T1, T2, T3, and M1
      descriptors. It is estimated that 10% to 15% of newly diagnosed lung cancer
      patients will be assigned a different disease stage as a result of these changes.

PMID- 22614970
TI  - Efficacy and safety of regorafenib in patients with metastatic and/or
      unresectable GI stromal tumor after failure of imatinib and sunitinib: a
      multicenter phase II trial.
AB  - PURPOSE: Metastatic GI stromal tumor (GIST) is a life-threatening disease with no
      therapy of proven efficacy after failure of imatinib and sunitinib. Regorafenib
      is a structurally unique inhibitor of multiple cancer-associated kinases,
      including KIT and platelet-derived growth factor receptor (PDGFR), with broad
      spectrum anticancer activity in preclinical and early-phase trials. Because KIT
      and PDGFR-alpha remain drivers of GIST after resistance to imatinib and
      sunitinib, we performed a multicenter single-stage phase II trial of regorafenib
      in patients with advanced GIST after failure of at least imatinib and sunitinib.
      PATIENTS AND METHODS: Patients received regorafenib orally, 160 mg daily, on days
      1 to 21 of a 28-day cycle. Disease assessment was performed every two cycles per
      RECIST 1.1. Primary end point was clinical benefit rate (CBR), defined as
      objective responses (ie, complete or partial response [PR] as well as stable
      disease [SD] >= 16 weeks). Serial tumor biopsies were obtained from consenting
      patients whenever possible. RESULTS: From February to December 2010, 34 patients
      were enrolled at four US centers. As of July 28, 2011, 33 patients had received
      at least two cycles of regorafenib (range, two to 17 cycles). CBR was 79% (95%
      CI, 61% to 91%). Four patients achieved PR, and 22 exhibited SD >= 16 weeks.
      Median progression-free survival was 10.0 months. The most common grade 3
      toxicities were hypertension and hand-foot-skin reaction. CONCLUSION: Regorafenib
      has significant activity in patients with advanced GIST after failure of both
      imatinib and sunitinib. A phase III trial of regorafenib versus placebo is
      ongoing to define more fully the safety and efficacy of regorafenib in this
      setting.

PMID- 22614971
TI  - Minimal residual disease-guided treatment deintensification for children with
      acute lymphoblastic leukemia: results from the Malaysia-Singapore acute
      lymphoblastic leukemia 2003 study.
AB  - PURPOSE: To improve treatment outcome for childhood acute lymphoblastic leukemia
      (ALL), we designed the Malaysia-Singapore ALL 2003 study with treatment
      stratification based on presenting clinical and genetic features and minimal
      residual disease (MRD) levels measured by polymerase chain reaction targeting a
      single antigen-receptor gene rearrangement. PATIENTS AND METHODS: Five hundred
      fifty-six patients received risk-adapted therapy with a modified Berlin-Frankfurt
      Munster-ALL treatment. High-risk ALL was defined by MRD >= 1 * 10(-3) at week 12
      and/or poor prednisolone response, BCR-ABL1, MLL gene rearrangements, hypodiploid
      less than 45 chromosomes, or induction failure; standard-risk ALL was defined by
      MRD <= 1 * 10(-4) at weeks 5 and 12 and no extramedullary involvement or high
      risk features. Intermediate-risk ALL included all remaining patients. RESULTS:
      Patients who lacked high-risk presenting features (85.7%) received remission
      induction therapy with dexamethasone, vincristine, and asparaginase, without
      anthracyclines. Six-year event-free survival (EFS) was 80.6% +/- 3.5%; overall
      survival was 88.4% +/- 3.1%. Standard-risk patients (n = 172; 31%) received
      significantly deintensified subsequent therapy without compromising EFS (93.2% +/
      4.1%). High-risk patients (n = 101; 18%) had the worst EFS (51.8% +/- 10%); EFS
      was 83.6% +/- 4.9% in intermediate-risk patients (n = 283; 51%). CONCLUSION: Our
      results demonstrate significant progress over previous trials in the region.
      Three-drug remission-induction therapy combined with MRD-based risk
      stratification to identify poor responders is an effective strategy for childhood
      ALL.

PMID- 22614974
TI  - Blindness: looking but not seeing.

PMID- 22614973
TI  - Atypical melanocytic proliferations and new primary melanomas in patients with
      advanced melanoma undergoing selective BRAF inhibition.
AB  - PURPOSE: Selective inhibition of mutant BRAF by using class I RAF inhibitors in
      patients with metastatic melanoma has resulted in impressive clinical activity.
      However, there is also evidence that RAF inhibitors might induce carcinogenesis
      or promote tumor progression via stimulation of MAPK signaling in RAF wild-type
      cells. We analyzed melanocytic lesions arising under class I RAF inhibitor
      treatment for dignity, specific genetic mutations, or expression of signal
      transduction molecules. PATIENTS AND METHODS: In all, 22 cutaneous melanocytic
      lesions that had either developed or considerably changed in morphology in 19
      patients undergoing treatment with selective BRAF inhibitors for BRAF-mutant
      metastatic melanoma at seven international melanoma centers within clinical
      trials in 2010 and 2011 were analyzed for mutations in BRAF and NRAS genes and
      immunohistologically assessed for expression of various signal transduction
      molecules in comparison with 22 common nevi of 21 patients with no history of
      BRAF inhibitor treatment. RESULTS: Twelve newly detected primary melanomas were
      confirmed in 11 patients within 27 weeks of selective BRAF blockade. In addition,
      10 nevi developed of which nine were dysplastic. All melanocytic lesions were
      BRAF wild type. Explorations revealed that expression of cyclin D1 and pAKT was
      increased in newly developed primary melanomas compared with nevi (P = .01 and P
      = .03, respectively). There was no NRAS mutation in common nevi, but BRAF
      mutations were frequent. CONCLUSION: Malignant melanocytic tumors might develop
      with increased frequency in patients treated with selective BRAF inhibitors
      supporting a mechanism of BRAF therapy-induced growth and tumorigenesis. Careful
      surveillance of melanocytic lesions in patients receiving class I RAF inhibitors
      seems warranted.

PMID- 22614972
TI  - Reduced-calorie dietary weight loss, exercise, and sex hormones in postmenopausal
      women: randomized controlled trial.
AB  - PURPOSE: Estrogens and androgens are elevated in obesity and associated with
      increased postmenopausal breast cancer risk, but the effect of weight loss on
      these biomarkers is unknown. We evaluated the individual and combined effects of
      a reduced-calorie weight loss diet and exercise on serum sex hormones in
      overweight and obese postmenopausal women. PATIENTS AND METHODS: We conducted a
      single-blind, 12-month, randomized controlled trial from 2005 to 2009.
      Participants (age 50 to 75 years; body mass index > 25.0 kg/m(2), exercising <
      100 minutes/wk) were randomly assigned using a computer-generated sequence to (1)
      reduced-calorie weight loss diet ("diet"; n = 118), (2) moderate- to vigorous
      intensity aerobic exercise ("exercise"; n = 117), (3) combined reduced-calorie
      weight loss diet and moderate- to vigorous-intensity aerobic exercise ("diet +
      exercise"; n = 117), or (4) control (n = 87). Outcomes were estrone concentration
      (primary) and estradiol, free estradiol, total testosterone, free testosterone,
      androstenedione, and sex hormone-binding globulin (SHBG) concentrations
      (secondary). RESULTS: Mean age and body mass index were 58 years and 30.9
      kg/m(2), respectively. Compared with controls, estrone decreased 9.6% (P = .001)
      with diet, 5.5% (P = .01) with exercise, and 11.1% (P < .001) with diet +
      exercise. Estradiol decreased 16.2% (P < .001) with diet, 4.9% (P = .10) with
      exercise, and 20.3% (P < .001) with diet + exercise. SHBG increased 22.4% (P <
      .001) with diet and 25.8% (P < .001) with diet + exercise. Free estradiol
      decreased 21.4% (P < .001) with diet and 26.0% (P < .001) with diet + exercise.
      Free testosterone decreased 10.0% (P < .001) with diet and 15.6% (P < .001) with
      diet + exercise. Greater weight loss produced stronger effects on estrogens and
      SHBG. CONCLUSION: Weight loss significantly lowered serum estrogens and free
      testosterone, supporting weight loss for risk reduction through lowering exposure
      to breast cancer biomarkers.

PMID- 22614975
TI  - Very superstitious.

PMID- 22614976
TI  - Early- and long-term outcome data of patients with pseudomyxoma peritonei from
      appendiceal origin treated by a strategy of cytoreductive surgery and
      hyperthermic intraperitoneal chemotherapy.
AB  - PURPOSE: Pseudomyxoma peritonei (PMP) originating from an appendiceal mucinous
      neoplasm remains a biologically heterogeneous disease. The purpose of our study
      was to evaluate outcome and long-term survival after cytoreductive surgery (CRS)
      and hyperthermic intraperitoneal chemotherapy (HIPEC) consolidated through an
      international registry study. PATIENTS AND METHODS: A retrospective multi
      institutional registry was established through collaborative efforts of
      participating units affiliated with the Peritoneal Surface Oncology Group
      International. RESULTS: Two thousand two hundred ninety-eight patients from 16
      specialized units underwent CRS for PMP. Treatment-related mortality was 2% and
      major operative complications occurred in 24% of patients. The median survival
      rate was 196 months (16.3 years) and the median progression-free survival rate
      was 98 months (8.2 years), with 10- and 15-year survival rates of 63% and 59%,
      respectively. Multivariate analysis identified prior chemotherapy treatment (P <
      .001), peritoneal mucinous carcinomatosis (PMCA) histopathologic subtype (P <
      .001), major postoperative complications (P = .008), high peritoneal cancer index
      (P = .013), debulking surgery (completeness of cytoreduction [CCR], 2 or 3; P <
      .001), and not using HIPEC (P = .030) as independent predictors for a poorer
      progression-free survival. Older age (P = .006), major postoperative
      complications (P < .001), debulking surgery (CCR 2 or 3; P < .001), prior
      chemotherapy treatment (P = .001), and PMCA histopathologic subtype (P < .001)
      were independent predictors of a poorer overall survival. CONCLUSION: The
      combined modality strategy for PMP may be performed safely with acceptable
      morbidity and mortality in a specialized unit setting with 63% of patients
      surviving beyond 10 years. Minimizing nondefinitive operative and systemic
      chemotherapy treatments before definitive cytoreduction may facilitate the
      feasibility and improve the outcome of this therapy to achieve long-term
      survival. Optimal cytoreduction achieves the best outcomes.

PMID- 22614977
TI  - Impact of cancer on work and education among adolescent and young adult cancer
      survivors.
AB  - PURPOSE: To examine the impact of cancer on work and education in a sample of
      adolescent and young adult (AYA) patients with cancer. PATIENTS AND METHODS: By
      using the Adolescent and Young Adult Health Outcomes and Patient Experience Study
      (AYA HOPE)-a cohort of 463 recently diagnosed patients age 15 to 39 years with
      germ cell cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma, sarcoma, and acute
      lymphocytic leukemia from participating Surveillance, Epidemiology, and End
      Results (SEER) cancer registries-we evaluated factors associated with return to
      work/school after cancer diagnosis, a belief that cancer had a negative impact on
      plans for work/school, and reported problems with work/school after diagnosis by
      using descriptive statistics, chi(2) tests, and multivariate logistic regression.
      RESULTS: More than 72% (282 of 388) of patients working or in school full-time
      before diagnosis had returned to full-time work or school 15 to 35 months
      postdiagnosis compared with 34% (14 of 41) of previously part-time
      workers/students, 7% (one of 14) of homemakers, and 25% (five of 20) of
      unemployed/disabled patients (P < .001). Among full-time workers/students before
      diagnosis, patients who were uninsured (odds ratio [OR], 0.21; 95% CI, 0.07 to
      0.67; no insurance v employer-/school-sponsored insurance) or quit working
      directly after diagnosis (OR, 0.15; 95% CI, 0.06 to 0.37; quit v no change) were
      least likely to return. Very intensive cancer treatment and quitting work/school
      were associated with a belief that cancer negatively influenced plans for
      work/school. Finally, more than 50% of full-time workers/students reported
      problems with work/studies after diagnosis. CONCLUSION: Although most AYA
      patients with cancer return to work after cancer, treatment intensity, not having
      insurance, and quitting work/school directly after diagnosis can influence
      work/educational outcomes. Future research should investigate underlying causes
      for these differences and best practices for effective transition of these cancer
      survivors to the workplace/school after treatment.

PMID- 22614978
TI  - BRAF/NRAS mutation frequencies among primary tumors and metastases in patients
      with melanoma.
AB  - PURPOSE: The prevalence of BRAF, NRAS, and p16CDKN2A mutations during melanoma
      progression remains inconclusive. We investigated the prevalence and distribution
      of mutations in these genes in different melanoma tissues. PATIENTS AND METHODS:
      In all, 291 tumor tissues from 132 patients with melanoma were screened. Paired
      samples of primary melanomas (n = 102) and synchronous or asynchronous metastases
      from the same patients (n = 165) were included. Tissue samples underwent mutation
      analysis (automated DNA sequencing). Secondary lesions included lymph nodes (n =
      84), and skin (n = 36), visceral (n = 25), and brain (n = 44) sites. RESULTS:
      BRAF/NRAS mutations were identified in 58% of primary melanomas (43% BRAF; 15%
      NRAS); 62% in lymph nodes, 61% subcutaneous, 56% visceral, and 70% in brain
      sites. Mutations were observed in 63% of metastases (48% BRAF; 15% NRAS), a
      nonsignificant increase in mutation frequency after progression from primary
      melanoma. Of the paired samples, lymph nodes (93% consistency) and visceral
      metastases (96% consistency) presented a highly similar distribution of BRAF/NRAS
      mutations versus primary melanomas, with a significantly less consistent pattern
      in brain (80%) and skin metastases (75%). This suggests that independent
      subclones are generated in some patients. p16CDKN2A mutations were identified in
      7% and 14% of primary melanomas and metastases, with a low consistency (31%)
      between secondary and primary tumor samples. CONCLUSION: In the era of targeted
      therapies, assessment of the spectrum and distribution of alterations in
      molecular targets among patients with melanoma is needed. Our findings about the
      prevalence of BRAF/NRAS/p16CDKN2A mutations in paired tumor lesions from patients
      with melanoma may be useful in the management of this disease.

PMID- 22614979
TI  - Addressing spirituality within the care of patients at the end of life:
      perspectives of patients with advanced cancer, oncologists, and oncology nurses.
AB  - PURPOSE: Attention to patients' religious and spiritual needs is included in
      national guidelines for quality end-of-life care, but little data exist to guide
      spiritual care. PATIENTS AND METHODS: The Religion and Spirituality in Cancer
      Care Study is a multi-institution, quantitative-qualitative study of 75 patients
      with advanced cancer and 339 cancer physicians and nurses. Patients underwent
      semistructured interviews, and care providers completed a Web-based survey
      exploring their perspectives on the routine provision of spiritual care by
      physicians and nurses. Theme extraction was performed following triangulated
      procedures of interdisciplinary analysis. Multivariable ordinal logistic
      regression models assessed relationships between participants' characteristics
      and attitudes toward spiritual care. RESULTS: The majority of patients (77.9%),
      physicians (71.6%), and nurses (85.1%) believed that routine spiritual care would
      have a positive impact on patients. Only 25% of patients had previously received
      spiritual care. Among patients, prior spiritual care (adjusted odds ratio [AOR],
      14.65; 95% CI, 1.51 to 142.23), increasing education (AOR, 1.26; 95% CI, 1.06 to
      1.49), and religious coping (AOR, 4.79; 95% CI, 1.40 to 16.42) were associated
      with favorable perceptions of spiritual care. Physicians held more negative
      perceptions of spiritual care than patients (P < .001) and nurses (P = .008).
      Qualitative analysis identified benefits of spiritual care, including supporting
      patients' emotional well-being and strengthening patient-provider relationships.
      Objections to spiritual care frequently related to professional role conflicts.
      Participants described ideal spiritual care to be individualized, voluntary,
      inclusive of chaplains/clergy, and based on assessing and supporting patient
      spirituality. CONCLUSION: Most patients with advanced cancer, oncologists, and
      oncology nurses value spiritual care. Themes described provide an empirical basis
      for engaging spiritual issues within clinical care.

PMID- 22614981
TI  - Benefits and adverse events in younger versus older patients receiving adjuvant
      chemotherapy for colon cancer: findings from the Adjuvant Colon Cancer Endpoints
      data set.
AB  - PURPOSE: Limited data exist regarding the outcomes of adjuvant therapy in younger
      patients with stage II and III colon cancer. We examined disease-free survival
      (DFS), overall survival (OS), recurrence-free interval (RFI), and grade 3+
      adverse events (AEs) in younger patients in the 33,574 patient Adjuvant Colon
      Cancer Endpoints Group data set. PATIENTS AND METHODS: Individual patient data
      from 24 randomized phase III clinical trials were obtained for survival outcomes,
      which included 10 clinical trials for AE outcomes. Two age-based cutoff points
      were used to define younger patients: age younger than 40 years and younger than
      50 years. Adjuvant therapy benefit analyses were limited to the nine clinical
      trials in which the investigational chemotherapeutic arm demonstrated benefit.
      RESULTS: One thousand seven hundred fifty-eight patients (5.2%) were younger than
      40 years, 5,817 patients (17.3%) were younger than 50 years, and only 299
      patients (0.9%) were younger than 30 years. No meaningful differences in sex or
      stage were noted in younger versus older patients. Younger and older patients did
      not differ in RFI (age, < 40 years: hazard ratio [HR], 1.0; P = .62 and age < 50
      years: HR, 1.02; P = .35). Younger patients (both cutoff points), had longer OS
      and DFS than older patients. In trials demonstrating adjuvant therapy benefit,
      similar DFS benefit was observed by age. Younger patients experienced less
      leukopenia and stomatitis, but more frequent nausea/vomiting. CONCLUSION: Among
      patients on clinical trials, younger and older patients with stage II and III
      colon cancer had similar RFI and adjuvant therapy benefit. Younger patients have
      longer OS and DFS, which is likely primarily because of fewer competing causes of
      death. Adjuvant therapy is beneficial for colon cancer in patients younger than
      50 years who meet typical clinical trial eligibility criteria.

PMID- 22614982
TI  - Journal Honors Andrew Lane, MD, PhD, As Recipient of the 2012 JCO Young
      Investigator Award.

PMID- 22614980
TI  - Cardiopulmonary function and age-related decline across the breast cancer
      survivorship continuum.
AB  - PURPOSE: To evaluate cardiopulmonary function (as measured by peak oxygen
      consumption [VO(2peak)]) across the breast cancer continuum and its prognostic
      significance in women with metastatic disease. PATIENTS AND METHODS: Patients
      with breast cancer representing four cross-sectional cohorts--that is, (1)
      before, (2) during, and (3) after adjuvant therapy for nonmetastatic disease, and
      (4) during therapy in metastatic disease--were studied. A cardiopulmonary
      exercise test (CPET) with expired gas analysis was used to assess VO(2peak). A
      Cox proportional hazards model was used to estimate the risk of death according
      to VO(2peak) category (< 15.4 v >= 15.4 mL . kg(-1) . min(-1)) with adjustment
      for clinical factors. RESULTS: A total of 248 women (age, 55 +/- 8 years)
      completed a CPET. Mean VO(2peak) was 17.8 +/- a standard deviation of 4.3 mL .
      kg(-1) . min(-1), the equivalent of 27% +/- 17% below age-matched healthy
      sedentary women. For the entire cohort, 32% had a VO(2peak) less than 15.4 mL .
      kg(-1) . min(-1)--the VO(2peak) required for functional independence. VO(2peak)
      was significantly different across breast cancer cohorts for relative (mL . kg(
      1) . min(-1)) and absolute (L . min(-1)) VO(2peak) (P = .017 and P < .001,
      respectively); VO(2peak) was lowest in women with metastatic disease. In patients
      with metastatic disease (n = 52), compared with patients achieving a VO(2peak) <=
      1.09 L . min(-1), the adjusted hazard ratio for death was 0.32 (95% CI, 0.16 to
      0.67, P = .002) for a VO(2peak) more than 1.09 L . min(-1). CONCLUSION: Patients
      with breast cancer have marked impairment in VO(2peak) across the entire
      survivorship continuum. VO(2peak) may be an independent predictor of survival in
      metastatic disease.

PMID- 22614983
TI  - Pseudomyxoma peritonei: more questions than answers.

PMID- 22614984
TI  - Risk assessment tool for distant recurrence after platinum-based concurrent
      chemoradiation in patients with locally advanced cervical cancer: a Korean
      gynecologic oncology group study.
AB  - PURPOSE: Our study aimed to develop a model to predict distant recurrence in
      locally advanced cervical cancer, which can be used to select high-risk patients
      in enriched clinical trials. PATIENTS AND METHODS: Our study was a retrospective
      analysis of a multi-institutional cohort of patients treated between 2001 and
      2009. According to the order of data submission, data from three institutions
      were allocated to a model development cohort (n = 434), and data from the
      remaining two institutions were allocated to an external validation cohort (n =
      115). Patient information including [(18)F]fluorodeoxyglucose positron emission
      tomography (FDG-PET) data and clinical outcome was modeled using competing risk
      regression analysis to predict 5-year cumulative incidence of distant recurrence.
      RESULTS: The competing risk analysis revealed that the following four parameters
      were significantly associated with distant recurrence: pelvic and para-aortic
      nodal positivity on FDG-PET, nonsquamous cell histology, and pretreatment serum
      squamous cell carcinoma antigen levels. This four-parameter model showed good
      discrimination and calibration, with a bootstrap-adjusted concordance index of
      0.70. Also, the validation set showed good discrimination with a bootstrap
      adjusted concordance index of 0.73. A user-friendly Web-based nomogram predicting
      5-year probability of distant recurrence was developed. CONCLUSION: We have
      developed a robust model to predict the risk of distant recurrence in patients
      with locally advanced cervical cancer. Further, we discussed how the selective
      enrichment of the patient population could facilitate clinical trials of systemic
      chemotherapy in locally advanced cervical cancer.

PMID- 22614985
TI  - Patient and physician decision styles and breast cancer chemotherapy use in older
      women: Cancer and Leukemia Group B protocol 369901.
AB  - PURPOSE Physician and patient decision styles may influence breast cancer care
      for patients >= 65 years ("older") because there is uncertainty about
      chemotherapy benefits in this group. We evaluate associations between decision
      making styles and actual treatment.   METHODS Data were collected from women
      treated outside of clinical trials for newly diagnosed stage I to III breast
      cancer (83% response) from January 2004 through April 2011 in 75 cooperative
      group sites. Physicians completed a one-time mailed survey (91% response), and
      clinical data were abstracted from charts. Patient decision style was measured on
      a five-point scale. Oncologists' preference for prescribing chemotherapy was
      based on standardized vignettes. Regression and multiple imputation were used to
      assess associations between chemotherapy and other variables.  Results There were
      1,174 women seen by 212 oncologists; 43% of women received chemotherapy. One
      third of women preferred to make their own treatment decision. Patient and
      physician decision styles were independently associated with chemotherapy. Women
      who preferred less physician input had lower odds of chemotherapy than women who
      preferred more input (odds ratio [OR] = 0.79 per 1-point change; 95% CI, 0.65 to
      0.97; P = .02) after considering covariates. Patients whose oncologists had a
      high chemotherapy preference had higher odds of receiving chemotherapy (OR =
      2.65; 95% CI, 1.80 to 3.89; P < .001) than those who saw oncologists with a low
      preference.   CONCLUSION Physicians' and older patients' decision styles are each
      associated with breast cancer chemotherapy use. It will be important to re
      evaluate the impact of decision styles when there is greater empirical evidence
      about the benefits and risks of chemotherapy in older patients.

PMID- 22614986
TI  - Choosing the best trastuzumab-based adjuvant chemotherapy regimen: should we
      abandon anthracyclines?

PMID- 22614987
TI  - Scarring, disfigurement, and quality of life in long-term survivors of childhood
      cancer: a report from the Childhood Cancer Survivor study.
AB  - PURPOSE: Childhood cancer survivors are at increased risk for adverse outcomes
      and chronic medical conditions. Treatment-related scarring, disfigurement, and
      persistent hair loss, in addition to their long-term impact on psychological
      distress or health-related quality of life (HRQOL), have received little
      attention. PATIENTS AND METHODS: Self-reported scarring/disfigurement and
      persistent hair loss were examined in 14,358 survivors and 4,023 siblings from
      the Childhood Cancer Survivor Study. Multivariable models were used to examine
      associations with demographic and cancer treatment. The impact of disfigurement
      and hair loss on HRQOL (ie, Medical Outcomes Short Form-36) and emotional
      distress (ie, Brief Symptom Inventory-18) was examined. RESULTS: Survivors
      reported a significantly higher rate of scarring/disfigurement compared with
      siblings for head/neck (25.1% v 8.4%), arms/legs (18.2% v 10.2%), and
      chest/abdomen (38.1% v 9.1%), as well as hair loss (14.0% v 6.3%). In age-, sex-,
      and race-adjusted models, cranial radiation exposure >= 36 Gy increased risk for
      head/neck disfigurement (relative risk [RR], 2.42; 95% CI, 2.22 to 2.65) and hair
      loss (RR, 4.24; 95% CI, 3.63 to 4.95). Adjusting for cranial radiation, age, sex,
      race, education, and marital status, survivor hair loss increased risk of anxiety
      (RR, 1.60; 95% CI, 1.23 to 2.07), whereas head/neck disfigurement increased risk
      of depression (RR, 1.19; 95% CI, 1.01 to 1.41). Limitations due to emotional
      symptoms were associated with head/neck disfigurement (RR, 1.24; 95% CI, 1.10 to
      1.41), arm/leg disfigurement (RR, 1.19; 95% CI, 1.05 to 1.35), and hair loss (RR,
      1.26; 95% CI, 1.09 to 1.47). CONCLUSION: Survivors of childhood cancer are at
      increased risk for disfigurement and persistent hair loss, which is associated
      with future emotional distress and reduced quality of life. Future studies are
      needed to better identify and manage functional outcomes in these patients.

PMID- 22614988
TI  - Decline in the use of anthracyclines for breast cancer.
AB  - PURPOSE: To determine the patterns of use of anthracycline- and taxane-based
      chemotherapy for breast cancer treatment. METHODS: Claims from a 5% national
      Medicare sample and from a nationally representative claims database (Marketscan)
      from 1998 to 2009 were used. Patients with International Classification of
      Diseases (ICD), ninth revision, codes indicating breast cancer, ICD and Common
      Procedural Terminology codes indicating breast surgery, and claims for
      chemotherapy between 3 months before and 12 months after surgery comprised the
      study cohort. Chemotherapy was classified as anthracycline-based or taxane-based,
      and the percentages of use were calculated. Piecewise regression models were used
      to identify the inflection points in the rates of chemotherapy use. The effect of
      patient characteristics on receiving different types of chemotherapy was
      estimated by multivariable logistic regression models. RESULTS: A total of 4,458
      patients were included in the Medicare cohort and 30,422 in the private insurance
      cohort. After 2005, a sharp increase in the use of taxane-based chemotherapy and
      a decline in anthracycline-based chemotherapy was seen. By 2008 in the Medicare
      cohort, 51% of patients received taxane-based and 32% received anthracycline
      based chemotherapy. By the end of 2008, the majority of patients younger than 65
      years were also receiving taxane-based chemotherapy. Patients younger than 35
      years were less likely to be treated with a taxane-based regimen, whereas
      patients who underwent 21-gene recurrence score testing and those treated with
      trastuzumab were more likely to receive taxane-based chemotherapy. CONCLUSION:
      The use of anthracycline-based chemotherapy has declined, and the majority of
      patients with breast cancer are instead receiving taxane-based chemotherapy. The
      potential impact on patient outcomes is unknown.

PMID- 22614990
TI  - Prognosis of colorectal cancer with peritoneal carcinomatosis: is a new staging
      necessary?

PMID- 22614989
TI  - Management of immune-related adverse events and kinetics of response with
      ipilimumab.
AB  - Monoclonal antibodies directed against the immune checkpoint protein cytotoxic T
      lymphocyte antigen-4 (CTLA-4; CD152)-ipilimumab and tremelimumab-have been
      investigated in metastatic melanoma and other cancers and have shown promising
      results. Recently, ipilimumab was approved by the US Food and Drug Administration
      for the treatment of metastatic melanoma. We review the literature on managing
      the adverse effects and kinetics of tumor regression with ipilimumab and provide
      guidelines on their management. During treatment with these antibodies, a unique
      set of adverse effects may occur, called immune-related adverse events (irAEs).
      These include rashes, which may rarely progress to life-threatening toxic
      epidermal necrolysis, and colitis, characterized by a mild to moderate, but
      occasionally also severe and persistent diarrhea. Hypophysitis, hepatitis,
      pancreatitis, iridocyclitis, lymphadenopathy, neuropathies, and nephritis have
      also been reported with ipilimumab. Early recognition of irAEs and initiation of
      treatment are critical to reduce the risk of sequelae. Interestingly, irAEs
      correlated with treatment response in some studies. Unique kinetics of response
      have been observed with CTLA-4 blockade with at least four patterns: (1) response
      in baseline lesions by week 12, with no new lesions seen; (2) stable disease,
      followed by a slow, steady decline in total tumor burden; (3) regression of tumor
      after initial increase in total tumor burden; and (4) reduction in total tumor
      burden during or after the appearance of new lesion(s) after week 12. We provide
      a detailed description of irAEs and recommendations for practicing oncologists
      who are managing them, along with the unusual kinetics of response associated
      with ipilimumab therapy.

PMID- 22614991
TI  - NEW and RENEW: building the case for weight loss in breast cancer.

PMID- 22614992
TI  - Occult nodal metastasis in non-small-cell lung cancer: implications for the
      radiation oncologist.

PMID- 22614993
TI  - Effects of a brief multimedia psychoeducational intervention on the attitudes and
      interest of patients with cancer regarding clinical trial participation: a
      multicenter randomized controlled trial.
AB  - PURPOSE: The negative attitudes of patients with cancer regarding clinical trials
      are an important contributor to low participation rates. This study evaluated
      whether a brief psychoeducational intervention was effective in improving
      patients' attitudes as well as their knowledge, self-efficacy for decision
      making, receptivity to receiving more information, and general willingness to
      participate in clinical trials. PATIENTS AND METHODS: A total of 472 adults with
      cancer who had not been asked previously to participate in a clinical trial were
      randomly assigned to receive printed educational information about clinical
      trials or a psychoeducational intervention that provided similar information and
      also addressed misperceptions and concerns about clinical trials. The primary
      (attitudes) and secondary outcomes (knowledge, self-efficacy, receptivity, and
      willingness) were assessed via patient self-report before random assignment and 7
      to 28 days later. RESULTS: Patients who received the psychoeducational
      intervention showed more positive attitudes toward clinical trials (P = .016) and
      greater willingness to participate (P = .011) at follow-up than patients who
      received printed educational information. Evidence of an indirect effect of
      intervention assignment on willingness to participate (estimated at 0.168; 95%
      CI, 0.088 to 0.248) suggested that the benefits of psychoeducation on willingness
      to participate were explained by the positive impact of psychoeducation on
      attitudes toward clinical trials. CONCLUSION: A brief psychoeducational
      intervention can improve the attitudes of patients with cancer toward clinical
      trials and thereby increase their willingness to participate in clinical trials.
      Findings support conducting additional research to evaluate effects of this
      intervention on quality of decision making and rates of participation among
      patients asked to enroll onto therapeutic clinical trials.

PMID- 22614994
TI  - Reach out to enhance wellness home-based diet-exercise intervention promotes
      reproducible and sustainable long-term improvements in health behaviors, body
      weight, and physical functioning in older, overweight/obese cancer survivors.
AB  - PURPOSE: Diet and exercise interventions have been tested in cancer survivors as
      a means to reduce late effects and comorbidity, but few have assessed adherence
      and health outcomes long term. METHODS: Between July 2005 and May 2007, the Reach
      Out to Enhance Wellness (RENEW) trial accrued 641 locoregionally staged, long
      term (>= 5 years from diagnosis) colorectal, breast, and prostate cancer
      survivors in the United States (21 states), Canada, and the United Kingdom. All
      participants were sedentary (< 150 minutes of physical activity [PA] a week),
      overweight or obese (body mass index, 25 to 40 kg/m(2)), and over age 65 years.
      The trial tested a diet-exercise intervention delivered via mailed print
      materials and telephone counseling. RENEW used a wait-list control, cross-over
      design (ie, participants received the year-long intervention immediately or after
      a 1-year delay), which allowed the opportunity to assess program efficacy
      (previously reported primary outcome), durability, and reproducibility (reported
      herein). Measures included diet quality (DQ), PA, BMI, and physical function
      (PF). RESULTS: No significant relapse was observed in the immediate-intervention
      arm for DQ, PA, and BMI; however, rates of functional decline increased when the
      intervention ceased. From year 1 to year 2, significant improvements were
      observed in the delayed-intervention arm; mean change scores in behaviors and BMI
      and PF slopes were as follows: DQ score, 5.2 (95% CI, 3.4 to 7.0); PA, 45.8
      min/wk (95% CI, 26.9 to 64.6 min/wk); BMI, -0.56 (95% CI, -0.75 to -0.36); and
      Short Form-36 PF, -1.02 versus -5.52 (P < .001 for all measures). Overall, both
      arms experienced significant improvements in DQ, PA, and BMI from baseline to 2
      year follow-up (P < .001). CONCLUSION: Older cancer survivors respond favorably
      to lifestyle interventions and make durable changes in DQ and PA that contribute
      to sustained weight loss. These changes positively reorient functional decline
      trajectories during intervention delivery.

PMID- 22614995
TI  - Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic
      anaplastic large-cell lymphoma: results of a phase II study.
AB  - PURPOSE: Systemic anaplastic large-cell lymphoma (ALCL) is an aggressive subtype
      of T-cell lymphoma characterized by the uniform expression of CD30. The antibody
      drug conjugate brentuximab vedotin delivers the potent antimicrotubule agent
      monomethylauristatin E to CD30-positive malignant cells. A phase II multicenter
      trial was conducted to evaluate the efficacy and safety of brentuximab vedotin in
      patients with relapsed or refractory systemic ALCL. PATIENTS AND METHODS:
      Patients with systemic ALCL and recurrent disease after at least one prior
      therapy received brentuximab vedotin 1.8 mg/kg intravenously every 3 weeks over
      30 minutes as an outpatient infusion. The primary end point of the study was
      overall objective response rate as assessed by independent central review.
      RESULTS: Of 58 patients treated in the study, 50 patients (86%) achieved an
      objective response, 33 patients (57%) achieved a complete remission (CR), and 17
      patients (29%) achieved a partial remission. The median durations of overall
      response and CR were 12.6 and 13.2 months, respectively. Grade 3 or 4 adverse
      events in >= 10% of patients were neutropenia (21%), thrombocytopenia (14%), and
      peripheral sensory neuropathy (12%). CONCLUSION: Brentuximab vedotin induced
      objective responses in the majority of patients and CRs in more than half of
      patients with recurrent systemic ALCL. Targeted therapy with this CD30-directed
      antibody-drug conjugate may be an effective treatment for relapsed or refractory
      systemic ALCL and warrants further studies in front-line therapy.

PMID- 22614996
TI  - Optimized protocol for derivation of human embryonic stem cell lines.
AB  - For the past 12 years, the biology and applications of human embryonic stem cells
      (hESCs) have received great attention from the scientific community. Derivatives
      of the first hESC line obtained by J. Thomson's group (Science 282(5391):1145
      1147, 1998) have been used in clinical trials in patients with spinal cord
      injury, and other hESC lines have now been used to generate cells for use in
      treating blindness (Lancet 379(9817):713-720, 2012). In addition to the classical
      protocol based on mouse or human feeder layers using open culture methods (In
      Vitro Cellular & Developmental Biology - Animal 46(3-4):386-394, 2010; Stem Cells
      23(9):1221-1227, 2005; Nature Biotechnology 24(2):185-187, 2006; Human
      Reproduction 21(2):503-511, 2006; Human Reproduction 20(8):2201-2206, 2005;
      Fertility and Sterility 83(5):1517-1529, 2005), novel hESC lines have been
      derived xeno-free (without using animal derived reagents) (PLoS One 5 (4):1024
      1026, 2010), feeder-free (without supporting cell monolayers) (Lancet
      365(9471):1601-1603, 2005), in microdrops under oil (In Vitro Cellular &
      Developmental Biology - Animal 46(3-4):236-41, 2010) and in suspension with ROCK
      inhibitor (Nature Biotechnology 28(4):361-4, 2010). Regardless of the culture
      system, successful hESC derivation usually requires optimization of embryo
      culture, the careful and timely isolation of its inner cell mass (ICM), and
      precise culture conditions up to the establishment of pluripotent cell growth
      during hESC line derivation. Herein we address the crucial steps of the hESC line
      derivation protocol, and provide tips to apply quality control to each step of
      the procedure.

PMID- 22614997
TI  - Microbial nanowires: a new paradigm for biological electron transfer and
      bioelectronics.
AB  - The discovery that Geobacter sulfurreducens can produce protein filaments with
      metallic-like conductivity, known as microbial nanowires, that facilitate long
      range electron transport is a paradigm shift in biological electron transfer and
      has important implications for biogeochemistry, microbial ecology, and the
      emerging field of bioelectronics. Although filaments in a wide diversity of
      microorganisms have been called microbial nanowires, the type IV pili of G.
      sulfurreducens and G. metallireducens are the only filaments that have been shown
      to be required for extracellular electron transport to extracellular electron
      acceptors or for conduction of electrons through biofilms. Studies of G.
      sulfurreducens pili preparations and intact biofilms under physiologically
      relevant conditions have provided multiple lines of evidence for metallic-like
      conduction along the length of pili and for the possibility of pili networks to
      confer high conductivity within biofilms. This mechanism of electron conduction
      contrasts with the previously known mechanism for biological electron transfer
      via electron tunneling or hopping between closely associated molecules, a
      strategy unlikely to be well adapted for long-range electron transport outside
      the cell. In addition to promoting electron exchange with abiotic electron
      acceptors, microbial nanowires have recently been shown to be involved in direct
      interspecies electron transfer between syntrophic partners. An improved
      understanding of the mechanisms for metallic-like conductivity in microbial
      nanowires, as well as engineering microorganisms with desirable catalytic
      abilities with nanowires, could lead to new applications in microbial
      electrosynthesis and bioelectronics.

PMID- 22614998
TI  - [The flight of the butterflies].

PMID- 22614999
TI  - Nicotine enhances proliferation, migration, and radioresistance of human
      malignant glioma cells through EGFR activation.
AB  - It has been suggested that continued tobacco use during radiation therapy
      contributes to maintenance of neoplastic growth despite treatment with radiation.
      Nicotine is a cigarette component that is an established risk factor for many
      diseases, neoplastic and otherwise. The hypothesis of this work is that nicotine
      promotes the proliferation, migration, and radioresistance of human malignant
      glioma cells. The effect of nicotine on cellular proliferation, migration,
      signaling, and radiation sensitivity were evaluated for malignant glioma U87 and
      GBM12 cells by use of the AlamarBlue, scratch healing, and clonogenic survival
      assays. Signal transduction was assessed by immunoblotting for activated EGFR,
      ERK, and AKT. At concentrations comparable with those found in chronic smokers,
      nicotine induced malignant glioma cell migration, growth, colony formation, and
      radioresistance. Nicotine increased phosphorylation of EGFR(tyr992), AKT(ser473),
      and ERK. These molecular effects were reduced by pharmacological inhibitors of
      EGFR, PI3K, and MEK. It was therefore concluded that nicotine stimulates the
      malignant behavior of glioma cells in vitro by activation of the EGFR and
      downstream AKT and ERK pathways.

PMID- 22615000
TI  - Medulloblastoma with focal divergent/teratoid differentiation.
AB  - Medulloblastomas with myogenic differentiation, previously termed
      medullomyoblastomas, form rare variants of medulloblastomas. Occasional tumors
      showing combined myogenic differentiation and melanotic tubular structures have
      also been described. On studying the records of a tertiary-care super specialty
      hospital, of 80 cases of medulloblastoma in a 5-year period, 36 showed nodular
      islands of neuronal, three myogenic, two glial, and one melanotic
      differentiation. Of the three cases of medulloblastomas with myogenic
      differentiation, we came across an extremely rare variant of medulloblastoma
      showing, in addition to the predominant primitive neuroectodermal component, a
      single minute nodular focus of 0.8 cm diameter, with divergent differentiation
      into mainly myogenic, epithelial, cartilaginous, and osseous lineages. Two
      ependymoblastic rosettes were also identified at different foci. In conclusion, a
      medulloblastoma with a small nodular island of divergent differentiation into
      various lineages has been seldom documented in literature. Microscopic foci of
      multilineage differentiation may be explained by the teratoid potential of
      medulloblastoma, or pluripotent nature of the neural crest cells, and requires
      extensive sampling for detection. It remains to be confirmed through more reports
      whether medulloblastomas with differentiation respond to a treatment protocol 
      similar to that of medulloblastomas.

PMID- 22615001
TI  - Silicate modulates the cross-talk between osteoblasts (SaOS-2) and osteoclasts
      (RAW 264.7 cells): inhibition of osteoclast growth and differentiation.
AB  - It has been shown that inorganic monomeric and polymeric silica/silicate, in the
      presence of the biomineralization cocktail, increases the expression of
      osteoprotegerin (OPG) in osteogenic SaOS-2 sarcoma cells in vitro. In contrast,
      silicate does not affect the steady-state gene expression level of the
      osteoclastogenic ligand receptor activator of NF-kappaB ligand (RANKL). In turn
      it can be expected that the concentration ratio of the mediators OPG/RANKL
      increases in the presence of silicate. In addition, silicate enhances the growth
      potential of SaOS-2 cells in vitro, while it causes no effect on RAW 264.7 cells
      within a concentration range of 10-100 uM. Applying a co-cultivation assay
      system, using SaOS-2 cells and RAW 264.7 cells, it is shown that in the presence
      of 10 uM silicate the number of RAW 264.7 cells in general, and the number of
      TRAP(+) RAW 264.7 cells in particular markedly decreases. The SaOS-2 cells retain
      their capacity of differential gene expression of OPG and RANKL in favor of OPG
      after exposure to silicate. It is concluded that after exposure of the cells to
      silicate a factor(s) is released from SaOS-2 cells that causes a significant
      inhibition of osteoclastogenesis of RAW 264.7 cells. It is assumed that it is an
      increased secretion of the cytokine OPG that is primarily involved in the
      reduction of the osteoclastogenesis of the RAW 264.7 cells. It is proposed that
      silicate might have the potential to stimulate osteogenesis in vivo and perhaps
      to ameliorate osteoporotic disorders.

PMID- 22615002
TI  - 11th Annual LVMH Recherche Symposium: skin rejuvenation.
AB  - The 11(th) Annual LVMH Recherche Scientific Symposium was held in London on
      October 27(th), into the warmth of the distinguished British Library, with nearly
      150 industry and research attendees. The meeting organized by LVMH Recherche was
      centered on the theme of skin rejuvenation. The current state of play for
      rejuvenation research was summarized, and then advances in the science of skin
      aging and rejuvenation therapies were discussed in detail. Personalized genomics
      and current and prospective translational therapies were presented, followed by a
      clever linking of multiple global theories towards a cohesive plan for future
      goals in rejuvenation research.

PMID- 22615003
TI  - Combining gold and palladium catalysis: one-pot access to pentasubstituted arenes
      from furan-yne and en-diyne substrates.
AB  - A series of furan-yne systems was transformed into the corresponding
      tetrasubstituted annelated phenol derivatives that bear one bromo group. The two
      step procedure consisted of a phenol synthesis and a subsequent electrophilic
      bromination with N-bromosuccinimide (NBS). The reactions can be performed in a
      one-pot procedure with the same precatalyst. The halogenation reaction is highly
      selective only in the presence of the gold catalyst. En-diyne substrates were
      also suitable starting materials; then the pentasubstituted aromatic core showed
      a completely different substitution pattern for the phenolic products.
      Furthermore, a one-pot protocol that consisted of a gold-catalyzed phenol
      synthesis, a gold-catalyzed halogenation reaction, and a palladium-catalyzed
      Suzuki coupling was established. The overall efficiency of this procedure was
      excellent and the substrate scope of the reaction was broad.

PMID- 22615006
TI  - Recognition by nonaromatic and stereochemical subunit-containing polyamides of
      the four Watson-Crick base pairs in the DNA minor groove.
AB  - In order to develop an optimal subunit as a T-recognition element in hairpin
      polyamides, 15 novel chirality-modified polyamides containing (R)-alpha,beta
      diaminopropionic acid ((R) beta alpha-NH 2), (S)-alpha,beta-diaminopropionic acid
      ((S) beta alpha-NH 2), (1R,3S)-3-aminocyclopentanecarboxylic acid ((RS) Cp),
      (1S,3R)-3-amino-cyclopentanecarboxylic acid ((RS) Cp), (1R,3R)-3
      aminocyclopentanecarboxylic acid ((RR) Cp) and (1S,3S)-3-amino
      cyclopentanecarboxylic acid ((SS) Cp) residues were synthesized. Their binding
      characteristics to DNA sequences 5'-TGCNCAT-3'/3'-ACGN'GTA-5' (N?N'=A?T, T?A, G?C
      and C?G) were systemically studied by surface plasmon resonance (SPR) and
      molecular simulation (MSim) techniques. SPR showed that polyamide 4, AcIm-(S)
      beta alpha-NH 2-ImPy-gamma-ImPy-beta-Py-betaDp (beta/(S) beta alpha-NH 2 pair),
      bound to a DNA sequence containing a core binding site of 5'-TGCACAT-3' with a
      dissociation equilibrium constant (K(D) ) of 4.5*10(-8)  m. This was a tenfold
      improvement in specificity over 5'-TGCTCAT-3' (K(D) =4.5*10(-7)  M). MSim studies
      supported the SPR results. More importantly, for the first time, we found that
      chiral 3-aminocyclopentanecarboxylic acids in polyamides can be employed as base
      readers with only a small decrease in binding affinity to DNA. In particular, SPR
      showed that polyamide 9 ((RR) Cp/beta pair) had a 15-fold binding preference for
      5'-TGCTCAT-3' over 5'-TGCACAT-3'. A large difference in standard free energy
      change for A?T over T?A was determined (DeltaDeltaG(o) =5.9 kJ mol(-1) ), as was
      a twofold decrease in interaction energy by MSim. Moreover, a 1:1 stoichiometry
      (9 to 5'-TGCTCAT-3'/3'-ACGAGTA-5') was shown by MSim to be optimal for the chiral
      five-membered cycle to fit the minor groove. Collectively, the study suggests
      that the (S)-alpha-amino-beta-aminopropionic acid and (1R,3R)-3
      aminocyclopentanecarboxylic acid can serve as a T-recognition element, and the
      stereochemistry and the nature of these subunits significantly influence binding
      properties in these recognition events. Subunit (1R,3R)-3
      aminocyclopentanecarboxylic acid broadens our scope to design novel polyamides.

PMID- 22615008
TI  - Does cheating pay: the role of externally supplied momentum on muscular force in
      resistance exercise.
AB  - Our work investigates the use of "external momentum" in the context of
      hypertrophy-oriented training. This is momentum supplied to the load (such as a
      dumbbell) used in an exercise by means of action of muscles not inherently
      involved in the exercise. We challenge the general consensus that the use of such
      momentum often described as "cheating" is counterproductive. We focus on the use
      of external momentum in the shoulder lateral raise and adopt a framework whereby
      exercise execution is simulated on a computer. This is achieved using a physical
      model of motion which is combined with anthropomorphic measurements and empirical
      data of muscular recruitment from previous work. The introduction of moderate
      momentum (producing initial angular velocities around 57.5 degrees  s(-1))
      increases the torque of the target muscles even without an increase in the load
      used. A moderate increase in the load and the use of momentum allows the torque
      to be increased even further. In contrast, excessive use of momentum results in
      lower demands on the target muscles, while an excessive increase of the load
      reduces the total hypertrophy stimulus by virtue of the decreased number of
      repetitions which can be performed successfully and thus the dramatically
      shortened time under tension. Our results disprove the conventional belief that
      the use of external momentum necessarily reduces the overload of the target
      muscles. A moderate use of external momentum increases both the per-repetition
      peak torque and the total hypertrophy stimulus in a set.

PMID- 22615009
TI  - Associations between Borg's rating of perceived exertion and physiological
      measures of exercise intensity.
AB  - Borg's rating of perceived exertion (RPE) is a widely used psycho-physical tool
      to assess subjective perception of effort during exercise. We evaluated the
      association between Borg's RPE and physiological exercise parameters in a very
      large population. In this cohort study, 2,560 Caucasian men and women [median age
      28 (IQR 17-44) years] completed incremental exercise tests on treadmills or cycle
      ergometers. Heart rate, blood lactate concentration, and RPE (Borg scale 6-20)
      were simultaneously measured at the end of each work load. Rating of perceived
      exertion was strongly correlated with heart rate (r = 0.74, p < 0.001) and blood
      lactate (r = 0.83, p < 0.001). The mean values for lactate threshold (LT) and
      individual anaerobic threshold corresponded to an RPE of 10.8 +/- 1.8 and 13.6 +/
      1.8, respectively. Fixed lactate thresholds of 3 and 4 mmol/L corresponded to
      RPEs of 12.8 +/- 2.1 and 14.1 +/- 2.0. Gender, age, coronary artery disease
      (CAD), physical activity status and exercise testing modality did not influence
      this association significantly (all p > 0.05). Borg's RPE seems to be an
      affordable, practical and valid tool for monitoring and prescribing exercise
      intensity, independent of gender, age, exercise modality, physical activity level
      and CAD status. Exercising at an RPE of 11-13 ("low") is recommended for less
      trained individuals, and an RPE of 13-15 may be recommended when more intense but
      still aerobic training is desired.

PMID- 22615010
TI  - Growth charts for individuals with Smith-Lemli-Opitz syndrome.
AB  - Smith-Lemli-Opitz syndrome (SLOS) is a rare multiple congenital anomaly
      neurodevelopmental syndrome of impaired cholesterol synthesis. Growth restriction
      and developmental delay are very common clinical manifestations of SLOS. The
      degree, etiology, and consequences of growth restriction in SLOS remain an area
      of limited knowledge to the scientific community. There have been no studies
      describing the growth parameters and providing reference growth charts for
      individuals with SLOS. Our longitudinal data from 78 patients between the ages of
      0.1 and 16 years with SLOS show a growth restriction of about two standard
      deviations below the Centers for Disease Control (CDC) norms for age. This study
      represents comprehensive anthropometric data from the largest cohort available,
      and proposes growth charts for widespread use in the management and study of
      individuals with SLOS.

PMID- 22615011
TI  - Barrett's esophagus and esophageal cancer: an overview.
AB  - Although esophageal cancer (EC) is the eighth most common cancer in several
      European countries, it is one of deadliest worldwide. The most frequent
      predisposing factor implicated in its development is Barrett's esophagus (BE), an
      acquired metaplastic transformation of the esophageal lining cells from normal
      squamous epithelium into specialised or intestinal-like columnar epithelium. The
      major risk factor for BE is gastroesophageal reflux disease. Although BE is in
      itself a benign and often asymptomatic disorder, its clinical importance stems
      from the recognition that it represents the main precursor lesion for the
      development of esophageal adenocarcinoma (AC), a tumor that is rapidly increasing
      especially in developed countries and is associated with a low survival rate.
      This paper provides an overview of the epidemiology and natural history of BE as
      well as of the possible pathogenetic mechanisms underlying the development of BE
      and its progressive transition to AC. New diagnostic tests are described,
      recommendations for screening and surveillance are provided and surgical and
      ablative procedures to treat dysplastic lesions and early neoplasia are
      discussed. Claimed chemopreventive agents and biomarkers that in the near future
      may help identify people with a higher risk of EC are also considered.

PMID- 22615012
TI  - Expression and clinical significance of UCH37 in human esophageal squamous cell
      carcinoma.
AB  - BACKGROUND: Ubiquitin carboxyl-terminal hydrolase 37 (UCH37), a member of the
      DUBs, was found to play an important role in oncogenesis through promoting some
      Proto-oncogenes' expression and stem cell-like characteristics in the cell in
      previous research. The aim of this study was to assess the value of UCH37 in
      predicting tumor recurrence after curative resection in esophageal squamous cell
      carcinoma (ESCC) patients. METHODS: We analyzed UCH37 protein expression in 111
      clinicopathologically characterized ESCC cases, from those who underwent curative
      resection between 2007 and 2008, by immunohistochemistry. The prognostic
      significance was assessed using Kaplan-Meier survival estimates and log-rank
      tests. RESULTS: We found that UCH37 expression was higher in the cancer tissue
      than in non-tumorous control tissue at protein level and was overexpressed in
      tumor tissues of recurrent patients. There was a significant difference of UCH37
      expression in patients categorized according to TNM stage (p = 0.038) and lymph
      nodes metastasis condition (p = 0.009). Univariate analyses revealed that UCH37
      was a significant predictor for overall survival and disease-free survival, and
      multivariate analyses showed that UCH37 was an independent prognostic marker for
      ESCC recurrence. A prognostic significance of UCH37 was also found in the
      subgroup of lymph nodes metastasis condition classification. About 90 % of the
      recurrent patients recurred within 2 years, of which 84.4 % were predicted by
      UCH37. CONCLUSION: UCH37 is associated with outcome and recurrence of ESCC and
      can be a novel predictor for poor prognosis of ESCC patients after curative
      resection.

PMID- 22615013
TI  - Proton pump inhibitors increase the incidence of bone fractures in hepatitis C
      patients.
AB  - BACKGROUND: While proton pump inhibitors (PPI) may increase the risk of bone
      fractures, the incidence of new bone fractures in a chronic hepatitis C virus
      (HCV) infected cohort, with or without PPI exposure, has not been explored.
      METHODS: A retrospective cohort study of the incidence of bone fractures over 10
      years in 9,437 HCV antibody positive patients in the Dallas VA Hepatitis C
      Registry was performed. The study endpoint was the incidence of verified new bone
      fractures per patient-years (pt-yrs) in PPI users compared to non-PPI users. PPI
      use was defined as those taking a PPI for >=360 days. Pt-yrs of exposure for PPI
      users began on the first PPI prescription date, and pt-yrs of exposure for non
      PPI users began with first date of any non-PPI prescription. For both HCV groups,
      the final date of patients' study duration was defined by end of PPI exposure,
      bone fracture occurrence, death or end of study evaluation period. Exclusion
      criteria included use of bone health modifying medications >=30 days. Statistical
      differences in fracture incidence between groups were determined by multivariate
      regression analysis. RESULTS: Among the total study population analyzed (n =
      2,573), 109 bone fractures occurred. Unadjusted bone fracture incidences were
      13.99/1,000 pt-yrs vs. 5.86/1,000 pt-yrs in PPI and non-PPI users, respectively.
      The adjusted hazard ratio for new bone fractures was 3.87 (95 % CI 2.46-6.08) (p
      < 0.001) in PPI users. CONCLUSIONS: In patients with chronic HCV, use of PPI for
      >1 year increased the risk of new bone fractures by more than threefold.

PMID- 22615014
TI  - Validation of a surgical technique for rat intestinal irradiation: potential side
      effects prevention by dietary grape phenolics.
AB  - AIMS: This study evaluates and defines the histological and biochemical
      consequences of irradiation on the Hauer-Jensen intestinal model and investigates
      the potential effects of dietary polyphenols. MAIN METHODS: Sprague-Dawley rats
      were orchiectomized, and an ileal loop was transposed to the left part of the
      scrotum, then irradiated 2 weeks after surgery with a single dose of 21 Gy (4.49
      Gy/min). Four groups of rats received either phenolic extracts from grape seeds
      (EGS) and from red wine (ACYS, EGT), or pure quercetin 3-O-beta-glucoside (Q3G),
      for 5 days before the irradiation and were sacrificed 2 weeks after. Antioxidant
      enzyme activities, i.e. superoxide dismutase (SOD) and glutathione peroxidase
      activity (GSHPx), and oxidative markers such as myeloperoxidase activity (MPO)
      and thiobarbituric acid reactive substances (MDA) were measured as well as
      cytokine-induced neutrophil chemoattractant level (CINC-1), a chemokine involved
      in inflammation. KEY FINDINGS: Irradiated rats exhibited a high radiation injury
      score (RIS) with a thickened serosa, mucosal loss and ulceration, and epithelial
      atypicality. Intestinal MPO activity and CINC-1 concentration were significantly
      increased in irradiated animals (60 and 66 %, respectively). Higher plasma MDA
      levels (58 %) and SOD activity (32 %) were accompanied by a reduced GSHPx
      activity (79 %). However, feeding phenolic extracts remarkably reduced levels of
      blood SOD activity (34 % on average), intestinal CINC-1 (25-75 % range) and MPO
      activity (36-84 %). Except for Q3G, phenolics preserved the intestinal structure.
      SIGNIFICANCE: These findings show that irradiation triggers an inflammation, and
      an oxidative stress by disturbing the pro-oxidant/antioxidant balance and
      indicate that phenolics supply exerts preventive effects against radio-induced
      intestinal impairment.

PMID- 22615015
TI  - Nonanesthesiologist-administered propofol versus midazolam and propofol, titrated
      to moderate sedation, for colonoscopy: a randomized controlled trial.
AB  - BACKGROUND: Nonanesthesiologist-administered propofol (NAAP) is controversial due
      to deep sedation concerns. AIM: The purpose of this study was to evaluate the
      feasibility of moderate sedation with two different NAAP regimens for
      colonoscopy. METHODS: This was a double-blinded, randomised, placebo-controlled
      trial allocating 135 consecutive outpatients to placebo (group P) or midazolam 2
      mg (group M+P) before NAAP targeted to moderate sedation. Depth of sedation every
      2 min throughout the procedure, propofol doses, recovery times, complications and
      patient and endoscopist satisfaction were measured. RESULTS: A total of 84 % of
      assessments of the depth of sedation were moderate. Mean induction (76 [40-150]
      vs. 53 [30-90]) and total propofol doses (mg) (136 [60-270] vs. 104 [50-190])
      were significantly higher for group P (p < 0.001). However, deep sedation was
      significantly more prevalent in group M+P in minutes 4 (16 vs. 1 %, p = 0.05), 6
      (20 vs. 3.5 %, p = 0.046) and 8 (17 vs. 1.8 %, p = 0.06) of the procedure,
      coinciding with midazolam peak action. From minute 8 on, moderate sedation was
      significantly deeper for M+P (p = 0.002). Early recovery time (6.8 min vs. 5.2, p
      = 0.007), but not discharge time (10.4 min vs. 9.8, p = 0.5), was longer for M+P.
      Pain perception (P 1.03 vs. M+P 0.3, p = 0.009) and patient satisfaction scores
      (P 9.4 vs. M+P 9.8, p = 0.047) were better for M+P. No major complications
      occurred. CONCLUSIONS: Moderate sedation was feasible with both NAAP regimens.
      Drug synergy in the midazolam plus propofol sedation regimen promotes a deeper
      and longer moderate sedation, improving patient satisfaction rates but prolonging
      early recovery time (Clinical Trials gov NCT01428882).

PMID- 22615016
TI  - Safety and prevention of complications in endoscopic sedation.

PMID- 22615017
TI  - Comparison of single- versus double-balloon assisted-colonoscopy for colon
      examination after previous incomplete standard colonoscopy.
AB  - BACKGROUND: Colonoscopy fails to achieve cecal intubation in 5-10 % of cases.
      Many of these cases can be completed using balloon-assisted colonoscopy, either
      with the single-balloon colonoscopy (SBC) or the double-balloon colonoscopy (DBC)
      techniques. AIM: To compare the completion rates of SBC and DBC in patients with
      previous incomplete conventional colonoscopy. METHODS: Between August 2009 and
      July 2011 either SBC or DBC was performed in 53 patients in whom previous
      conventional colonoscopy did not achieve cecal intubation. The medical records of
      these 53 patients were reviewed retrospectively for details regarding (1)
      indication for the initial colonoscopy, (2) patient characteristics, (3) data
      from the initial colonoscopy, and (4) details on both SBC and DBC. RESULTS: SBC
      was successful in intubating the cecum in 100 % (26/26) of patients and DBC was
      successful in 93 % (25/27) of patients. The median (range) time to reach the
      cecum was 17 (9-43) min in the SBC group and 20 (7-58) min in the DBC group (P =
      0.37). The presence of polyps was an entirely new finding in 35 % (9/26) of
      patients in the SBC group and 30 % (8/27) of patients in DBC group. Therapeutics
      were performed in 73 % (19/26) of patients in SBC group and 67 % (18/27) of
      patients in DBC group. CONCLUSION: For patients with incomplete conventional
      colonoscopy, SBC and DBC offer high cecal intubation rates as well as detection
      of additional polyps and therapeutic capability. Either SBC or DBC can be
      considered after incomplete conventional colonoscopy.

PMID- 22615018
TI  - Balanced propofol sedation versus propofol monosedation in therapeutic
      pancreaticobiliary endoscopic procedures.
AB  - BACKGROUND: Prolonged or complex endoscopic procedures are frequently performed
      under deep sedation. However, no studies of therapeutic ERCP have yet compared
      the use of balanced propofol sedation (BPS) to propofol alone, titrated to
      moderate levels of sedation. AIM: This prospective, randomized, double-blind
      study was planned to compare the sedation efficacy and safety of BPS (propofol in
      combination with midazolam and fentanyl) and propofol monosedation in therapeutic
      ERCP and EUS. METHODS: BPS, or propofol monosedation titrated to a moderate level
      of sedation, was performed by trained registered nurses under endoscopist
      supervision. The main outcome measurements included sedation efficacy focusing on
      recovery time, sedation safety, endoscopic procedure outcomes, and complications.
      RESULTS: There were no significant differences in sedation efficacy, safety,
      procedure outcomes, and complications, with the exception of recovery time. Mean
      recovery time (standard deviation) was 18.37 (7.86) min in BPS and 13.4 (6.24)
      min in propofol monosedation (P < 0.001). In a safety analysis, cardiopulmonary
      complication rates related to BPS and propofol monosedation were 7.8 % (8/102)
      and 9.6 % (10/104), respectively (P = 0.652). No patient required assisted
      ventilation or permanent termination of a procedure in either group. Technical
      success of the endoscopic procedures was 96.3 and 97.2 %, respectively (P =
      0.701). Endoscopic procedure-related complications and outcomes did not differ
      depending on sedation procedure. CONCLUSIONS: Propofol monosedation by trained,
      registered sedation nurses under supervision resulted in a more rapid recovery
      time than BPS. There were no differences in the sedation safety, endoscopic
      procedure outcomes, and complications between BPS and propofol monosedation.

PMID- 22615019
TI  - Transforming growth factor beta1 gene variation Leu10Pro affects secretion and
      function in hepatic cells.
AB  - BACKGROUND: Our previous work revealed transforming growth factor beta1
      (TGFbeta1) gene polymorphisms are associated with susceptibility to
      hepatocellular carcinoma and liver cirrhosis. However, no further study of
      functional substitution in hepatic cells has yet been reported. AIMS: This study
      was designed to uncover the functional mechanisms of TGFbeta1 gene polymorphisms
      in the pathogenesis of liver diseases. METHODS: Two recombinant TGFbeta1
      expression plasmids containing TGFbeta1 codon 10 Leu/Pro variation were
      constructed with CMV promoter and transfected into human hepatoma cell lines
      (HepG2 and SMMU 7721), hepatic stellate cells (LX-2), and immortalized
      hepatocytes (L02). The secretion capacities of TGFbeta1 protein in the
      transfected cells were determined by ELISA. Apoptosis, proliferative activity,
      and expression of CD 105, CD83, and CD80 were also measured by use of flow
      cytometry. RESULTS: The ELISA results showed that cells transfected with CMV
      Pro10 were more capable of TGFbeta1 secretion than those transfected with CMV
      Leu10. Functionally, CMV-Pro10 was more apoptosis-protective and induced more
      proliferation than CMV-Leu10 in transfected hepatic cells. Pro10 up-regulated
      expression of CD105 and down-regulated expression of CD83. CONCLUSIONS: TGFbeta1
      gene Leu10Pro variation in signal peptide has significant effects on TGFbeta1
      secretion and functions in hepatic cells.

PMID- 22615020
TI  - Gut bacterial translocation contributes to microinflammation in experimental
      uremia.
AB  - BACKGROUND: Microinflammation frequently develops in chronic uremia with
      pathological intestinal changes. However, the relationship between gut bacterial
      translocation and microinflammation in uremia has not been widely investigated.
      AIM: This study aimed to investigate whether gut microbiome dysbiosis and
      translocation occurred in experimental uremia, and whether they consequently
      contributed to microinflammation. METHODS: Forty rats underwent surgical renal
      mass 5/6 ablation. The surviving (uremic group, n = 21) and healthy (sham group,
      n = 20) rats were used in the experiment. Postoperative blood, livers, spleens,
      and mesenteric lymph nodes (MLNs) were subjected to bacterial 16S ribosomal DNA
      amplification to determine if bacteria were present. Bacterial genomic DNA
      samples from the MLNs and colon were amplified with specific primers designed by
      the 16S rRNA sequence of the species obtained from blood, livers, and spleens.
      Pyrosequencing was used to analyze the colonic microbiome of each subject.
      Intestinal permeability to (99m)Tc-DTPA, plasma hs-CRP, and IL-6 were measured.
      RESULTS: Bacterial DNA in extraintestinal sites and altered colonic microbiomes
      were detected in some rats in the uremic group. Bacterial genomic DNA in MLNs and
      colon were obtained by primers specific for bacterial species observed from
      blood, livers, and spleens of identical individuals. Intestinal permeability,
      plasma hs-CRP, and IL-6 levels were statistically higher in the uremic group
      compared with the sham group. Plasma hs-CRP and IL-6 were significantly higher in
      uremic rats with bacterial DNA in their blood than in those without. CONCLUSIONS:
      Gut microbiome dysbiosis occurs and bacteria translocate to the systemic and
      lymph circulation, thereby contributing to microinflammation in experimental
      uremia.

PMID- 22615021
TI  - Additional biliary cannulation methods in patients with juxtapapillary duodenal
      diverticula.
AB  - BACKGROUND AND AIMS: Juxtapapillary diverticula (JPD) can increase the difficulty
      of biliary cannulation. A number of additional methods have been defined in case
      of failed cannulation attempt by standard technique. We aimed to investigate the
      more commonly preferred and practical additional methods among them. METHODS: A
      total of 1,205 endoscopic retrograde cholangiopancreatographies (ERCP) performed
      during a study period of 14 months were prospectively entered into a database. Of
      these, 222 (18 %) had JPD (123 women, 99 men, mean age 69 years) and 983 had no
      diverticula (523 women, 460 men, mean age 57 years). Additional cannulation
      methods used in patients with JPD were recorded. Biliary cannulation time, total
      procedure time, use of pre-cut papillotomy, and therapeutic success of ERCP were
      compared between the groups as well. RESULTS: Biliary cannulation was performed
      by standard technique in 210 patients with JPD (94.5 %). Cannulation was achieved
      by placement of a guidewire into the pancreatic duct in 6 (2.7 %) and use of two
      devices in one channel in 2 (0.9 %) patients. There was no significant difference
      between the total procedure time and therapeutic success of ERCP between the
      groups. Cannulation time was significantly longer in patients with JPD. Pre-cut
      papillotomy was performed less in patients with JPD. CONCLUSION: Presence of JPD
      does not decrease the therapeutic success of ERCP. Placement of a guidewire in
      the pancreatic duct or use of two-devices-in-one-channel are practical,
      successful, safe, and preferred methods which can be used in patients with failed
      cannulation by standard technique.

PMID- 22615022
TI  - Student characteristics as predictors of teachers' implementation of a
      kindergarten readiness program.
AB  - Recent years have seen increasing numbers of classroom-based interventions
      designed to enhance the school readiness of at-risk preschoolers. Even the most
      comprehensive, well-designed programs can suffer from limited effectiveness due
      to low-frequency implementation by teachers. The current study presents findings
      from the Building Bridges (BB) project, an integrated program targeting school
      readiness in Head Start and low-income child care centers. Previous studies have
      reported the role of teacher-level and program-level characteristics in
      predicting teacher implementation of an intervention. The present study examines
      the role of student characteristics-language and math ability, social skills, and
      behavioral functioning-in predicting implementation exposure. These associations
      were examined in the context of program type (Head Start, child care) and
      intervention condition (consultation, no consultation). 88 classrooms (41 Head
      Start, 47 child care) participated in the BB intervention. Implementation
      exposure was predicted by several distinct student characteristics. Teachers
      whose students exhibited poorer language skills implemented significantly more BB
      activities, a finding that was consistent across program types and intervention
      conditions. A marginally significant trend was identified for oppositional
      behavior when interacted with intervention group in that teachers whose students
      demonstrated higher rates of oppositional behavior implemented fewer intervention
      activities when they did not have a consultant. Teachers in child care centers
      with a BB consultant had higher rates of implementation than did teachers in all
      other groups. These findings provide important information regarding the student
      level characteristics that should be evaluated in order to optimize
      implementation of an intervention.

PMID- 22615024
TI  - Endoscopic-assisted tonsillectomy.

PMID- 22615023
TI  - On electron transport through Geobacter biofilms.
AB  - Geobacter spp. can form a biofilm that is more than 20 MUm thick on an anode
      surface by utilizing the anode as a terminal respiratory electron acceptor. Just
      how microbes transport electrons through a thick biofilm and across the
      biofilm/anode interface, and what determines the upper limit to biofilm thickness
      and catalytic activity (i.e., current, the rate at which electrons are
      transferred to the anode), are fundamental questions attracting substantial
      attention. A significant body of experimental evidence suggests that electrons
      are transferred from individual cells through a network of cytochromes associated
      with cell outer membranes, within extracellular polymeric substances, and along
      pili. Here, we describe what is known about this extracellular electron transfer
      process, referred to as electron superexchange, and its proposed role in biofilm
      anode respiration. Superexchange is able to account for many different types of
      experimental results, as well as for the upper limit to biofilm thickness and
      catalytic activity that Geobacter biofilm anodes can achieve.

PMID- 22615025
TI  - [Infection control management and practice in home care - analysis of structure
      quality].
AB  - BACKGROUND: Surveillance of infection control management and practices in home
      care is an important task of the public health service. While infection control
      aspects in residential homes for the aged and nursing are increasingly being
      discussed this subject has been poorly recognised in home care. AIM: The aim of
      this study was to identify problems in hygiene regarding the transmission of
      infectious diseases as well as quality assessment in home care. Based on the
      results of this study implications for infection control in home care facilities
      for public health services should be developed. METHOD: Statistical analyses were
      performed on the primary quality assessment data of home care facilities
      collected by the medical service of health insurances via computer-assisted
      personal interviews between March 2006 and March 2009. Structure quality in 194
      home care facilities was analysed as well as human resources and organisational
      conditions. Analyses were also done in the context of the clients' risk factor
      load. All analyses were performed by stratifying for the size of the home care
      services. To assess how the involved characteristics vary according to the size
      of the home care services chi-square tests and non-parametric tests were
      calculated. RESULTS: About 80% of the assessed home care services disposed of an
      infection control management plan. Compared to larger services smaller home care
      services, especially services with less than 10 clients had a poor structure in
      infection control management and practice. They also carried a higher load of
      risk factors in clients. The larger services had significantly less human
      resources. CONCLUSIONS: Surveillance of infection control management and
      practices by the public health services should focus on the structure of the
      smaller home care services. At the same time smaller home care services should be
      supported by offering training for the staff or counselling regarding hygiene
      related aspects. Furthermore, the outcome quality of the larger home care
      services with poorer human resources (one full-time nurse cares for more than 10
      dependants) should also be assessed in the frame of infection surveillance.

PMID- 22615026
TI  - [Restraint in hospitals - a sore point].
AB  - Restraints are used for several medical situations. Their use in restraining
      patients in psychiatric care and nursing homes is widely debated, whereas those
      in hospitals are rarely discussed. This is a particular cause of concern because
      restraints are prescribed under various circumstances in hospitals and yet they
      have an ambivalent character because they are viewed as a custodial measure. The
      aim of this paper is to examine the civil law legislation on restraints and
      medical reasons for employing restraints in German hospitals. I will argue that
      the use of restraints should only be performed after a thorough assessment of the
      patient and his or her wishes. As a vulnerable group, patients are dependent on
      clinical staff members, who must in all circumstances do their best to respect
      the autonomy and rights of their patients. Awareness of health-care personnel
      regarding the use of restraints should be increased and interdisciplinary
      collaboration among judges, clinicians and nurses must be bridged and enhanced in
      order to improve the flow and exchange of information on this very ethical and
      moral issue.

PMID- 22615027
TI  - [Does telemonitoring lead to health and economic benefits in patients with
      chronic heart failure? - a systematic review].
AB  - Chronic heart failure is a severe and common disease combined with high costs for
      the German health care system. Deficiencies in standard therapy and limited
      financial capacities of the German health care system necessitate new approaches
      in the care of chronic heart failure patients.The present study aims to analyse
      the scientific level of knowledge of clinical, economic and other outcomes of
      telemonitoring compared with standard therapy for patients with chronic heart
      failure. Results should provide an evidence base for health-care decision
      makers.To determine the outcomes, a systematic review was carried out by using
      the database MEDLINE. In accordance with defined inclusion and exclusion
      criteria, 10 randomized controlled trials remained. Furthermore, 4 studies of a
      hand research and the recently published results of one of the largest national
      studies were included.As a result of the systematic review, there is currently no
      evidence for the benefits of telemonitoring compared with standard therapy.
      National studies identified significant improvements or a tendency for
      improvements in terms of quality of life and costs/cost-effectiveness as well as
      partly in mortality, hospital duration and medication adherence. International
      studies diverged in their results. The comparability and validity of the
      investigated studies are limited due to a low number of national studies,
      different settings of the telemonitoring programmes, the inclusion of different
      NYHA classes, the heterogeneity of study endpoints and endpoint-related causes,
      short observation periods of some studies as well as questionable transferability
      of international cost-results to the German health care system. Furthermore,
      differences in standard therapy between national and international studies were
      identified. None of the international studies performed a comparison between
      clinical and economic outcomes.With regard to the future prospects of
      telemonitoring in Germany there is still a need for further high quality studies
      (particularly on the national level) concerning the clinical, economic and other
      outcomes of telemonitoring compared with standard therapy. Clear evidence is a
      sine qua non for telemonitoring's inclusion in the benefits catalogue of the
      statutory health insurance. For a better comparability of studies, standardised
      telemonitoring programmes and study criteria should be developed and applied.

PMID- 22615028
TI  - [Outcome evaluation of a health promotion among the elderly].
AB  - The programme "active health promotion in old age" focuses on responsible self
      determination in old age (empowerment) and places special emphasis on physical
      activity and nutrition. The intervention, successfully conducted in an urban
      setting (Hamburg), was tested in a rural area (Kinzigtal, Baden-Wuerttemberg). In
      this paper we present the results of the outcome evaluation. The intervention
      group consisted of older people, without care need and without cognitive
      impairment who lived in their own home (N=468). For the evaluation of the results
      a pre-post comparison was conducted (2 measuring points within an interval of 12
      months). 4 out of 5 participants reported changes in their behaviour after the
      intervention. However, the pre-post comparison shows significant changes only for
      nutrition behaviour, but not of physical activity. Health related quality of life
      (SF-36) did not change after 12 months. These findings indicate that health
      promotion in old age may lead to changes in nutrition behaviour.

PMID- 22615029
TI  - [Does the resident care assessment instrument improve long-term home care? -
      results of a nation-wide study in Germany].
AB  - BACKGROUND: Effective and efficient instruments for care planning and controlling
      are required to optimise the nursing process and improve outcome quality despite
      of various lacks of quality and precarious circumstances. METHODS: A cluster
      randomised controlled trial was conducted to assess whether the implementation of
      the Resident Assessment Instrument (RAI) into home care service providers can
      help to improve or stabilise functional abilities (ADL, IADL) and cognitive
      skills (MMST), improve quality of life (EQ-5D), reduce institutionalisation and
      thereby increase outcome quality. RESULTS: A comparison of mean differences
      between the treatment and control group showed no significant effects. Although
      the multilevel regression results show that clients in the treatment group fared
      better in terms of ADL and IADL (smaller decline) and were less likely to move to
      nursing homes and be hospitalised, none of these effects are significant.
      CONCLUSIONS: The lack of significance might be due to the fact that RAI was not
      fully implemented and even the partial implementation lasted much longer than
      expected. Moreover, the number of clients included in the study was smaller than
      originally planned.

PMID- 22615030
TI  - Sex-stratified socio-economic gradients in physical inactivity, obesity, and
      diabetes: evidence of short-term changes in Argentina.
AB  - OBJECTIVES: To evaluate how socio-economic gradients in NCDs and NCD-related risk
      factors change over time. METHODS: Secondary analysis of cross-sectional data
      from the 2005 and 2009 Argentine National Risk Factor Surveys (N = 41,392 and N =
      34,732) was conducted. We analyzed inequalities in three risk factors (low
      physical activity, obesity, and diabetes) according to income and educational
      attainment. The analysis was based on sex-stratified and age-adjusted logistic
      regression. RESULTS: The overall prevalence of low physical activity, obesity,
      and diabetes increased from 2005 to 2009. Increases occurred in most of the
      income and education groups, but females with the lowest socio-economic status
      generally showed the highest increases. In 2005, differences in physical
      inactivity among women with different levels of education were not statistically
      significant. By 2009, women with low education (OR = 1.57, 95 % CI = 1.34-1.84)
      and medium education (OR = 1.18, 95 % CI = 1.06-1.32) were more likely than women
      with high education to be physically inactive. CONCLUSION: Inequalities in
      physical inactivity, obesity, and diabetes have grown in Argentina over a short
      period of time.

PMID- 22615031
TI  - Ciliated cyst of the vulva in an elderly woman.

PMID- 22615032
TI  - Morphological homogeneity of neurons: searching for outlier neuronal cells.
AB  - We report a morphology-based approach for the automatic identification of outlier
      neurons, as well as its application to the NeuroMorpho.org database, with more
      than 5,000 neurons. Each neuron in a given analysis is represented by a feature
      vector composed of 20 measurements, which are then projected into a two
      dimensional space by applying principal component analysis. Bivariate kernel
      density estimation is then used to obtain the probability distribution for the
      group of cells, so that the cells with highest probabilities are understood as
      archetypes while those with the smallest probabilities are classified as
      outliers. The potential of the methodology is illustrated in several cases
      involving uniform cell types as well as cell types for specific animal species.
      The results provide insights regarding the distribution of cells, yielding single
      and multi-variate clusters, and they suggest that outlier cells tend to be more
      planar and tortuous. The proposed methodology can be used in several situations
      involving one or more categories of cells, as well as for detection of new
      categories and possible artifacts.

PMID- 22615033
TI  - Integrated biogas upgrading and hydrogen utilization in an anaerobic reactor
      containing enriched hydrogenotrophic methanogenic culture.
AB  - Biogas produced by anaerobic digestion, is mainly used in a gas motor for heat
      and electricity production. However, after removal of CO(2) , biogas can be
      upgraded to natural gas quality, giving more utilization possibilities, such as
      utilization as autogas, or distant utilization by using the existing natural gas
      grid. The current study presents a new biological method for biogas upgrading in
      a separate biogas reactor, containing enriched hydrogenotrophic methanogens and
      fed with biogas and hydrogen. Both mesophilic- and thermophilic anaerobic
      cultures were enriched to convert CO(2) to CH(4) by addition of H(2) . Enrichment
      at thermophilic temperature (55 degrees C) resulted in CO(2) and H(2)
      bioconversion rate of 320 mL CH(4) /(gVSS h), which was more than 60% higher than
      that under mesophilic temperature (37 degrees C). Different dominant species were
      found at mesophilic- and thermophilic-enriched cultures, as revealed by PCR-DGGE.
      Nonetheless, they all belonged to the order Methanobacteriales, which can mediate
      hydrogenotrophic methanogenesis. Biogas upgrading was then tested in a
      thermophilic anaerobic reactor under various operation conditions. By continuous
      addition of hydrogen in the biogas reactor, high degree of biogas upgrading was
      achieved. The produced biogas had a CH(4) content, around 95% at steady-state, at
      gas (mixture of biogas and hydrogen) injection rate of 6 L/(L day). The increase
      of gas injection rate to 12 L/(L day) resulted in the decrease of CH(4) content
      to around 90%. Further study showed that by decreasing the gas-liquid mass
      transfer by increasing the stirring speed of the mixture the CH(4) content was
      increased to around 95%. Finally, the CH(4) content around 90% was achieved in
      this study with the gas injection rate as high as 24 L/(L day).

PMID- 22615034
TI  - The synthetic purine reversine selectively induces cell death of cancer cells.
AB  - The synthetic purine reversine has been shown to possess a dual activity as it
      promotes the de-differentiation of adult cells, including fibroblasts, into stem
      cell-like progenitors, but it also induces cell growth arrest and ultimately cell
      death of cancer cells, suggesting its possible application as an anti-cancer
      agent. Aim of this study was to investigate the mechanism underneath reversine
      selectivity in inducing cell death of cancer cells by a comparative analysis of
      its effects on several tumor cells and normal dermal fibroblasts. We found that
      reversine is lethal for all cancer cells studied as it induces cell
      endoreplication, a process that malignant cells cannot effectively oppose due to
      aberrations in cell cycle checkpoints. On the other hand, normal cells, like
      dermal fibroblasts, can control reversine activity by blocking the cell cycle,
      entering a reversible quiescent state. However, they can be induced to become
      sensitive to the molecule when key cell cycle proteins, e.g., p53, are silenced.

PMID- 22615037
TI  - The role of percutaneous US-guided drainage in the treatment of splenic abscess.
      Case report and review of the literature.
AB  - Splenic abscess is an uncommon but potentially life-threatening disease that
      generally occurs in patients with neoplasia, immunodeficiency,
      hemoglobinopathies, trauma, metastatic infection, splenic infarction and
      diabetes. Splenic abscess should be considered in a patient with fever, left
      upper abdominal pain, and leukocytosis. Splenectomy has been the gold standard
      treatment for splenic abscess, however, burdened by high morbidity rate related
      clinical conditions of the patient. With the recent development of minimally
      invasive techniques and percutaneous US- or CT-guided procedures, the placement
      of a drainage has achieved excellent results with resolution of the disease in a
      high percentage of cases with low morbidity and negligible mortality.
      Percutaneous drainage is indicated for uniloculated or biloculated abscesses and
      for high risk surgical patients. It is a reliable technique with a high rate of
      therapeutical success and low costs compared to surgery. Other advantages include
      avoiding risks of intra-abdominal spillage and perioperative complications and
      saving time, along with a better patient compliance and an easier nursing care.
      The authors describe a case of splenic abscess treated by percutaneous US-guided
      drainage. Our results suggest that ultrasound-guided percutaneous drainage is a
      safe and feasible alternative to surgery in the treatment of splenic abscesses.
      In addition, it allows spleen preservation.

PMID- 22615036
TI  - Surgical management by means of electroretinographic examination during
      extracorporeal circulation.
AB  - BACKGROUND: Neurological and/or neuropsychological damages are important
      complications of cardiosurgical interventions. This study determined if the
      timing of the electroretinographic (ERG) ocular exam can assess intraoperative
      brain damage of patients supported by extracorporeal circulation (ECC) during
      cardiosurgical interventions. MATERIALS AND METHODS: The authors illustrate an
      ERG technique being able to evaluate on 12 patients during cardiosurgical
      interventions and in conditions of ECC, both hypothermic and normothermic, the
      possibility to forecast the potential neurological and/or neuropsychological
      damages. RESULTS: The ERG waves obtained are compared before and after ECC in
      various conditions of corporeal temperature. During ECC all patients had a change
      of ERG waves, whom was particularly significant for patients operated in
      conditions of induced hypothermia. CONCLUSIONS: The observations reported by ERG
      provide new and important information in support of the potential organic
      suffering. This exam can assess the defect of the waves indicative of
      insufficient ocular and brain perfusion of patients supported by ECC during
      cardiosurgical interventions.

PMID- 22615038
TI  - Morgagni hernia: technical variation in the laparoscopic treatment.
AB  - INTRODUCTION: Morgagni hernia is a rare entity that accounts for 3-5% of
      diaphragmatic hernias. They are mostly asymptomatic and discovered incidentally.
      Surgical treatment is indicated once diagnosis is made. Abdominal or thoracic
      accesses are possible using open or minimally invasive technique. METHODS: We
      report two cases of laparoscopic assisted repair of Morgagni hernia conducted by
      primary closure of the diaphragmatic defect with extracorporeal nonabsorbable
      sutures anchoring the diaphragmatic edge at the muscular fascia of the abdominal
      wall. RESULTS: Both patients had an uneventful postoperative recovery. The
      operative time was 90 and 60 minutes and the postoperative hospitalization was 4
      and 2 days respectively. CONCLUSIONS: Laparoscopic intervention for Morgagni
      hernia repair is easy, safe and less invasive compared to the open one, with
      reduced hospitalization time. Primary closure of the diaphragmatic defect with
      extracorporeal nonabsorbable sutures is an effective technique for Morgagni
      hernia; defects larger than 20-30 cm2 should be repaired using a prosthetic
      patch.

PMID- 22615039
TI  - Abdominal compartment syndrome due to a giant multilobulated ovarian serous
      cystadenoma. Case report and review of the literature.
AB  - The Authors report a case of abdominal compartment syndrome due to a giant
      ovarian serous cystadenoma. Despite of the relief of intra-abdominal hypertension
      (IAP: 16 mmHg), mild symptomatology (clinostatic dyspnea) lead to defer the
      emergency surgical treatment; after CT scan of abdomen and pelvis was performed a
      resection en bloc of the cystic mass, oophorectomy and cholecystectomy. However
      it seems advisable to perform an emergency laparotomy in patients with abdominal
      compartment syndrome (ACS) grade II when presenting as an acute abdomen.

PMID- 22615040
TI  - Therapeutic options in locally advanced thyroid carcinoma. Our experience.
AB  - INTRODUCTIONS: Thyroid cancer is the most common endocrine malignancy with an
      incidence equal to 1% of all malignant tumors. Prognostic factors affecting
      survival are manifold, including in several classifications (AMES, AGES, CORN and
      TNM). In this sense, the invasion of adjacent structures is one of the most
      important variables. The authors describe the experience of a single center in
      surgical treatment of advanced thyroid cancer. MATERIALS AND METHODS: Between
      1986 and 2010 , 1565 patients were undergoing surgery with thyroid cancer. In
      particular, 1403 interventions were made for differentiated cancer, 97 for
      medullary carcinoma, 25 for insular carcinoma, 29 for anaplastic carcinoma, 2 for
      plasmacytoma, and 7 for lymphoma and 2 for angiosarcoma. Among these 896 showed
      invasion of adjacent structures and / or distant metastases. RESULTS: There were
      no perioperative deaths or major complications. Surgical procedures consisted of:
      13 loboistmectomy, 519 total thyroidectomy (TT), 325 TT with lymphadenectomy of
      the central compartment, 7 TT with radical lymphectomy, 621 TT with functional
      lymphectomy, 6 TT with breast lumpectomy, 5 TT with with video-assisted lung
      metastasectomy, 16-TT with resection and tracheal anastomosis, 6 TT with
      laryngotracheal resection, 3 TT with laryngectomy, 4 TT with trachetomy, 28 TT
      with respiratory stent placement, 12 tracheotomy. At present, 1328 patients were
      free of disease, while 104 showed recurrence. Total of 133 deaths were recorded,
      all linked to disease relapse. DISCUSSION: The role of surgery in the treatment
      of advanced thyroid cancer is still undeniable. In the presence of extracapsular
      trespassing, in fact, the adoption of interventions demolition permits long-term
      survival, given the lack of aggressiveness of the tumor differentiated
      representing the majority of cases. The aim of surgical radicalization addition,
      even in the presence of distant metastases, it is justified by the possibilities
      offered by the therapeutic radioiodine treatment, which is not feasible in the
      presence of significant amounts of thyroid tissue which picks. In the presence of
      undifferentiated tumors, finally, endoscopic or surgical treatment may be
      indicated by simple purpose of palliation of respiratory symptoms.

PMID- 22615041
TI  - Intercostal muscle flap to protect the bronchial stump in pediatric lobectomy for
      lung abscess.
AB  - Lung suppurative diseases in children are usually responsive to medical treatment
      or percutaneous drainage. Rarely, pulmonary resection is required for lung
      abscess in childhood, particularly in presence of co-morbidities. In these cases,
      a lobectomy is usually performed through an open thoracotomy, with a reported
      incidence of bronco-pleural fistula up to 9.1% of pediatric series. This
      consequence is mainly due to the inflammatory condition; however the lack of
      knowledge of pediatric and thoracic surgeons with this rare condition in
      childhood can also play a role. In adults with lung cancer, the buttressing of
      bronchial stump with the additional support of an intercostal muscle (ICM) flap
      has proved to prevent this complication, as well as to reduce post-operative
      pain. We report the first pediatric experience of ICM flap used in 2
      immunocompetent children requiring lobectomy for suppurative lung conditions. Our
      preliminary experience confirms the feasibility of protecting the bronchial stump
      after lobectomy in children, especially in conditions at risk for bronco-pleural
      fistula development.

PMID- 22615043
TI  - A rare case of colon cancer with splenic abscess.
AB  - Cancer of the colon does not always present with the familiar symptoms.
      Perforation and penetration of adjacent organs, with abscess formation as the
      initial presentation, is uncommon. Splenic abscess is a rare clinical entity. The
      four causes of a splenic abscess described are: primary pyogenic infection,
      splenic trauma, hemoglobinopathies and contiguous disease. In this paper we
      report a case of splenic abscess from colon cancer in an 50-year-old man who had
      a left lower chest contusion two-week before and review pertinent literature.
      Only 11 reported cases of splenic abscess from colorectal cancer were found in
      Medline.

PMID- 22615044
TI  - Cystosarcoma phylloides of the breast: a rare diagnosis. A case report and review
      of the literature.
AB  - Sarcoma of the breast is a rare condition, with one possible meaning of relapse
      ad metastastasize, and behaves biologically as a stromal tumor. Surgery is the
      first choise and mastectomy is the best procedure adopted in these tumors. The
      aim of our study was to assess diagnostic and treatment options for PT, based on
      a review of the literature and our experience with a case of breast sarcoma
      arising from a phyllodes tumor.

PMID- 22615046
TI  - Clinical analysis of macrophage activation syndrome in pediatric patients with
      autoimmune diseases.
AB  - Macrophage activation syndrome (MAS) belongs to secondary hemophagocytic
      lymphohistiocytosis (HLH) syndrome. It is usually associated with rheumatic
      diseases. We retrospectively reviewed our hospital's medical records of 102
      HLH/MAS patients from the past 20 years. Demographics, clinical data, treatment,
      and outcomes were analyzed. Among 102 patients, eight patients with underlying
      juvenile systemic lupus erythematous (two patients), mixed connective tissue
      disease (one patient), primary anti-phospholipid syndrome (one patient), and
      systemic type juvenile rheumatoid arthritis (sJRA; four patients) with 13
      episodes of MAS were studied. Clinical manifestations of MAS included fever (100
      %), hepatosplenomegaly (77 %), lymphadenopathy (38 %), skin rash (62 %), and
      neurological involvement (31 %). Laboratory features included leukopenia (54 %),
      anemia (46 %), thrombocytopenia (77 %), jaundice (27 %), hypofibrinogenemia (40
      %), decreased erythrocyte sedimentation rate (67 %), and elevated liver enzymes
      (77 %), lactate dehydrogenase (100 %), ferritin (88 %), triglycerides (91 %), C
      reactive protein (85 %), plasma D-dimer (50 %), and hemophagocytosis in bone
      marrow (83 %). The Epstein-Barr virus and adenovirus infection triggered MAS in
      two patients with sJRA. Methylprednisolone pulse therapy was effective in two out
      of three patients, and high-dose intravenous immunoglobulin (IVIG) was effective
      in two out of six patients. Patients with sJRA responded well to corticosteroids
      and cyclosporine. Complications included opportunistic infection with
      Pneumocystis jiroveci, multiple organ failure, and intensive care unit myopathy.
      The mortality rate was one out of eight (12.5 %). Our results showed that MAS
      could be fatal and complicate various pediatric autoimmune diseases. It generally
      has a good response to corticosteroids and IVIG. Prompt recognition and timely
      treatment can result in good outcomes.

PMID- 22615045
TI  - Long-term outcomes after surgical resection for gastric cancer liver metastasis:
      an analysis of 64 macroscopically complete resections.
AB  - PURPOSE: The indication for hepatectomy in cases of gastric cancer liver
      metastases (GLM) remains unclear and it remains controversial whether surgical
      resection is beneficial for GLM. The objective of this retrospective study was to
      clarify the indications for and benefit of hepatectomy for GLM. METHODS: Seventy
      three patients underwent hepatectomies for GLM from January 1993 to January 2011.
      Macroscopically complete (R0 or R1) resection was achieved in 64 patients. Among
      them, 32 patients underwent synchronous hepatectomy with gastrectomy and the
      remaining 32 patients underwent metachronous hepatectomy. Repeat hepatectomy was
      done in 14 patients for resectable intrahepatic recurrences. Clinicopathological
      factors were evaluated by univariate and multivariate analyses among patients who
      received macroscopically complete resection for those affecting survival.
      RESULTS: The overall 1-, 3-, and 5-year survival rates after macroscopically
      complete (R0 or R1) liver resection (n = 64) for GLM were 84, 50, and 37 %,
      respectively, with a median survival of 34 months. Univariate analysis identified
      serosal invasion of the primary gastric cancer and blood transfusions during
      surgery as poor prognosis indicators. By multivariate analysis, serosal invasion
      of the primary gastric cancer and larger hepatic tumor (>5 cm in diameter) were
      found to be independent indicators of poor prognosis. CONCLUSIONS: GLM patients
      with the maximum diameter of hepatic tumors of <5 cm and without serosal invasion
      of the primary gastric cancer are the best candidate for hepatectomy.

PMID- 22615047
TI  - Relationship of general self-efficacy with anxiety, symptom severity and quality
      of life in cancer patients before and after radiotherapy treatment.
AB  - PURPOSE: Treatment-related symptoms can increase psychological and physical
      distress and alter the patient's quality of life. The present study evaluates
      prospectively treatment-related symptoms, general self-efficacy, anxiety and
      quality of life (QoL) in patients with different types of cancer undergoing
      external beam radiotherapy (RT) and the relationship of patients' general self
      efficacy with the assessed measures, at the baseline and their absolute change 1
      month after the end of the treatment. METHODS: The sample consisted of 90 cancer
      patients. General self-efficacy was assessed using the General Perceived Self
      efficacy (GSE). QoL was evaluated using the Linear Analogue Scale Assessment
      (LASA), anxiety with the Anxiety subscale of the Hospital Anxiety and Depression
      (HAD) scale, whereas symptom severity and interference were assessed using the MD
      Anderson Symptom Inventory (MDASI). The instruments were administered first at
      the beginning of the RT and then 1 month after the completion of the RT. RESULTS:
      At post-treatment, general self-efficacy was reduced (28.86 +/- 6.42), anxiety
      scores were elevated (9.56 +/- 4.42), QoL scores were reduced (6.74 +/- 1.81) and
      symptoms severity were deteriorated (3.24 +/- 2.62). Pre-treatment and post
      treatment absolute change scores revealed statistically significant negative
      correlations between general self-efficacy absolute scores and anxiety (p <
      0.0005). Moderate negative correlations between general self-efficacy absolute
      scores and symptoms (MDASI symptom severity: p = 0.003, symptom interference: p =
      0.002), whereas a low positive correlation was found between general self
      efficacy absolute scores and LASA energy scale (p = 0.048). CONCLUSIONS: A sense
      of self-efficacy and its relationship with anxiety, symptom distress and quality
      of life are important factors for patients receiving radiotherapy. Health care
      professionals need to be aware of anxiety, symptom severity and patient's quality
      of life prior to treatment initiation.

PMID- 22615048
TI  - Dehalogenation of an anthropogenic compound by an engineered variant of the mouse
      cytokine macrophage migration inhibitory factor.
AB  - An unconventional dehalogenase: An engineered variant (I64V/V106L) of the mouse
      cytokine macrophage migration inhibitory factor (MIF) promiscuously catalyzes the
      hydrolytic dehalogenation of the xenobiotic organohalogen trans-3-chloroacrylic
      acid to acetaldehyde. Although the dehalogenase activity of this MIF variant is
      quite low, it achieves an ~10(9) -fold rate enhancement, matching those of
      conventional enzymes acting on their natural substrates.

PMID- 22615049
TI  - Association between common genetic variant of HRH2 and gastric cancer risk.
AB  - Histamine plays important physiological roles in the upper gastrointestinal tract
      and acts via the H2 receptor. The -1018 G>A (rs2067474) in an enhancer element of
      the promoter and non-synonymous rs79385261 (Asn46Thr) were identified in HRH2. We
      attempted to clarify the associations of these polymorphisms with gastric
      carcinogenesis. The study was performed in 321 patients with gastric cancer and
      599 subjects with no evidence of gastric malignancies on upper gastroduodenal
      endoscopy. The genotypes were determined using a one-tube multiplex PCR-SSCP
      method. The degree of gastritis was assessed in 496 subjects and serum pepsinogen
      (PG) I/II levels were measured in 124 subjects without gastric cancer. The minor
      allele of Asn46Thr could not be detected. The frequencies of the -1018 A allele
      in the non-GC and GC groups were 13.5% and 8.26%, respectively (p=0.00077).
      Overall, -1018 GG homozygotes had an increased risk for developing gastric cancer
      (OR 1.68; 95% CI 1.17-2.42; p=0.0052), especially intestinal type cancer (OR
      1.94; 95% CI 1.23-3.08; p=0.0047). In subjects aged >60 years, the adjusted risk
      for gastric cancer among individuals who were -1018 GG homozygotes was 1.87
      (range 1.19-2.93; p=0.0065) compared with A carriers. In the gastric cancer cases
      located in the antrum and at comparative advanced stage, -1018 GG homozygosity
      was a significantly increased risk factor. In subjects >60 years, the metaplasia
      score was significantly higher in -1018 GG homozygotes than A carriers. Both
      atrophy and metaplasia scores were significantly increased with age only in -1018
      GG homozygotes. The PG I/II ratio was significantly decreased in H. pylori
      positive GG homozygotes than negative GG homozygotes and positive A carriers. Our
      results suggest that -1018 GG homozygosity of HRH2 may be associated with the
      severity of gastric mucosal atrophy. This genotype has an increased risk for the
      subsequent development of gastric cancer, especially intestinal type, at advanced
      age.

PMID- 22615050
TI  - DOTAGA-anhydride: a valuable building block for the preparation of DOTA-like
      chelating agents.
AB  - A DOTA derivative that contains an anhydride group was readily synthesized by
      reacting DOTAGA with acetic anhydride and its reactivity was investigated.
      Opening the anhydride with propylamine led to the selective formation of one of
      two possible regioisomers. The structure of the obtained isomer was unambiguously
      determined by 1D and 2D NMR experiments, including COSY, HMBC, and NOESY
      techniques. This bifunctional chelating agent offers a convenient and attractive
      approach for labeling biomolecules and, more generally, for the synthesis of a
      large range of DOTA derivatives. The scope of the reaction was extended to
      prepare DOTA-like compounds that contained various functional groups, such as
      isothiocyanate, thiol, ester, and amino acid moieties. This versatile building
      block was also used for the synthesis of a bimodal tag for SPECT or PET/optical
      imaging.

PMID- 22615051
TI  - In vitro rapid evolution of fungal immunomodulatory proteins by DNA family
      shuffling.
AB  - Fungal immunomodulatory proteins (FIPs) found in a wide variety of mushrooms hold
      significant therapeutic potential. Despite much research, the structural
      determinants for their immunomodulatory functions remain unknown. In this study,
      a DNA shuffling technique was used to create two shuffled FIP protein libraries:
      an intrageneric group containing products of shuffling between FIP-glu (FIP gene
      isolated from Ganoderma lucidum) and FIP-gsi (FIP gene isolated from Ganoderma
      sinense) genes and an intergeneric group containing the products of shuffling
      between FIP-glu, FIP-fve (FIP gene isolated from Flammulina velutipes), and FIP
      vvo (FIP gene isolated from Volvariella volvacea) genes. The gene shuffling
      generated 426 and 412 recombinant clones, respectively. Using colony blot
      analysis, we selected clones that expressed relatively high levels of shuffled
      gene products recognized by specific polyclonal antibodies. We analyzed the DNA
      sequences of the selected shuffled genes, and testing of their protein products
      revealed that they maintained functional abilities to agglutinate blood cells and
      induce cytokine production by splenocytes from Kunming mice in vitro. Meanwhile,
      the relationships between protein structure and the hemagglutination activity and
      between the changed nucleotide sites and expression levels were explored by
      bioinformatic analysis. These combined analyses identified the nucleotide changes
      involved in regulating the expression levels and hemagglutination activities of
      the FIPs. Therefore, we were able to generate recombinant FIPs with improved
      biological activities and expression levels by using DNA shuffling, a powerful
      tool for the generation of novel therapeutic proteins and for their structural
      and functional studies.

PMID- 22615052
TI  - Bioreactor studies predict whole microbial population dynamics in oil sands
      tailings ponds.
AB  - Microorganisms in oil sands fluid fine tailings (FFT) are critical to
      biogeochemical elemental cycling as well as to the degradation of residual
      hydrocarbon constituents and subsequent methane and CO2 production. Microbial
      activity enhances particulate matter sedimentation rates and the dewatering of
      FFT materials, allowing water to be recycled back into bitumen extraction. A bulk
      of this evidence comes from bioreactor studies and has implications for
      engineering and environmental management of the FFT ponds. Yet, it is largely
      uncertain whether such laboratory populations are representative of whole field
      scale microbial communities. By using population ecology tools, we compared whole
      microbial communities present in FFT bioreactors to reference populations
      existing in Syncrude's West In Pit (WIP) tailings pond. Bacteria were found to be
      persistent in a sulfidic zone in both the oxic and anoxic bioreactors at all
      occasions tested. In contrast to the WIP, archaea only became predominant in
      bioreactors after 300 days, at which point analysis of similarity (global R
      statistic p<0.5) revealed no significant dissimilarities between the populations
      present in either system. A whole community succession pattern from bacterial
      dominated prevalence to a new assemblage predominated by archaea was suggested.
      These results have implications for the stepwise development of microbial model
      systems for predictive management of field scale FFT basins.

PMID- 22615053
TI  - Capability of yeast derivatives to adhere enteropathogenic bacteria and to
      modulate cells of the innate immune system.
AB  - Yeast derivatives including yeast cell wall components are promising alternatives
      to antibiotics with respect to the promotion of health and performance in
      livestock, based on their capacity to bind enteropathogenic bacteria and to
      beneficially modulate the immune system. However, these mode(s) of action both in
      vitro and in vivo are still not well understood. Furthermore, standardization and
      reproducibility of in vitro techniques (microbiology, cell culture assays) are
      critical features for the application of yeast derivatives as well as for the
      proof of effectiveness. Yeast cell wall products are suggested as anti-adhesive
      agents and are thus proposed to prevent attachment of certain intestinal bacteria
      by providing alternative adhesion sites to enterobacteria, which contain mannose
      specific type I fimbriae such as Escherichia coli or Salmonella spp. and which is
      well documented. Various in vitro assay techniques have become of paramount
      importance for biotechnological research since they allow for determination and
      quantification of potential mode(s) of action. However, in vitro assays may be
      criticized by product end users as not accurately reflecting in vivo responses.
      Pro and cons of different assays and their bias will be discussed specifically
      regarding yeast cell wall components and adhesion of enteropathogenic bacteria.
      Immunomodulation is a therapeutic approach intervening in auto-regulating
      processes of the defense system. Yeast derivatives such as beta-glucans are
      proposed to interact with cells of the innate immune system by receptor
      recognition. Controversial data in literature and mode(s) of action are reviewed
      and discussed here.

PMID- 22615055
TI  - Effect of ZnO and TiO2 nanoparticles preilluminated with UVA and UVB light on
      Escherichia coli and Bacillus subtilis.
AB  - We evaluated the effects of zinc oxide (ZnO) and titanium dioxide (TiO2)
      nanoparticles (NPs) preilluminated with ultraviolet light on Escherichia coli and
      Bacillus subtilis. The experiments were conducted using three different types of
      light: visible, Ultraviolet A (UVA, 315-400 nm), and Ultraviolet B (UVB, 280-315
      nm). The bacteria were exposed to NPs, either as liquid suspensions for growth
      inhibition assays or on agar plates for colony forming unit (CFU) assays. We
      found that the ZnO NPs were more toxic when preilluminated with UVA or UVB light
      than with visible light in both growth inhibition and CFU assays. TiO2 NPs were
      not toxic to the bacteria under UVA or UVB preillumination conditions. The photo
      dissolution of ZnO NPs increased with UV preillumination, which could explain the
      observed toxicity of ZnO NPs. We detected oxidative stress elicited by
      photoactive nanoparticles by measuring superoxide dismutase activity. The results
      of this study show that the toxicity of photoactive nanoparticles can be
      increased by UV preillumination by dissolution of toxic ions, which suggests the
      potential for preillumination-dependent toxicity of nanoparticles on soil
      environments in low light or darkness.

PMID- 22615054
TI  - Novel physiological roles for glutathione in sequestering acetaldehyde to confer
      acetaldehyde tolerance in Saccharomyces cerevisiae.
AB  - In this work, we identified novel physiological functions of glutathione in
      acetaldehyde tolerance in Saccharomyces cerevisiae. Strains deleted in the genes
      encoding the enzymes involved in glutathione synthesis and reduction, GSH1, GSH2
      and GLR1, exhibited severe growth defects compared to wild-type under
      acetaldehyde stress, although strains deleted in the genes encoding glutathione
      peroxidases or glutathione transferases did not show any growth defects. On the
      other hand, intracellular levels of reduced glutathione decreased in the presence
      of acetaldehyde in response to acetaldehyde concentration. Moreover, we show that
      glutathione can trap a maximum of four acetaldehyde molecules within its molecule
      in a non-enzymatic manner. Taken together, these findings suggest that
      glutathione has an important role in acetaldehyde tolerance, as a direct
      scavenger of acetaldehyde in the cell.

PMID- 22615056
TI  - Impact of Azotobacter exopolysaccharides on sustainable agriculture.
AB  - Recently, increasing attention have lead to search other avenue of biofertilizers
      with multipurpose activities as a manner of sustainable soil health to improve
      the plant productivity. Azotobacter have been universally accepted as a major
      inoculum used in biofertilizer to restore the nitrogen level into cultivated
      field. Azotobacter is well characterized for their profuse production of
      exopolysaccharides (EPS). Several reviews on biogenesis and multifunctional role
      of Azotobacter EPS have been documented with special emphasis on industrial
      applications. But the impact of Azotobacter EPS in plant growth promotion has not
      received adequate attention. This review outlines the evidence that demonstrates
      not only the contribution of Azotobacter EPS in global nutrient cycle but also
      help to compete successfully in different adverse ecological and edaphic
      conditions. This also focuses on new insights and concepts of Azotobacter EPS
      which have positive effects caused by the biofilm formation on overall plant
      growth promotion with other PGPRs. In addition, their potentials in agricultural
      improvement are also discussed. Recent data realized that Azotobacter EPS have an
      immense agro-economical importance including the survivability and maintenance of
      microbial community in their habitat. This leads us to confirm that the next
      generation Azotobacter inoculum with high yielding EPS and high nitrogen fixing
      ability can be utilized to satisfy the future demand of augmented crop production
      attributed to increase plant growth promoting agents.

PMID- 22615058
TI  - A Phase I trial of the kinesin spindle protein (Eg5) inhibitor AZD4877 in
      patients with solid and lymphoid malignancies.
AB  - BACKGROUND: This Phase I study assessed the safety and maximum tolerated dose
      (MTD) of the kinesin spindle protein inhibitor AZD4877 in patients with
      relapsed/refractory solid tumors and lymphoma. METHODS: In this multicenter
      study, a standard 3 + 3 dose-escalation design was used. AZD4877 was given as an
      intravenous infusion on days 1, 4, 8 and 11 of each 21-day cycle. Responses were
      assessed with CT scans +/- PET after 6 and 12 weeks, then every 12 weeks while on
      therapy. An additional four patients with lymphoma were enrolled at the MTD.
      RESULTS: 29 patients were enrolled and 22 patients received at least one dose of
      AZD4877 and were evaluable for safety. The MTD was 11 mg. Dose-limiting toxicity
      was neutropenia (n = 2 patients, 15 mg cohort). The most common adverse events
      were grade 1/2 fatigue, nausea, neutropenia and dyspnea. AZD4877 exposure
      generally increased with dose, with mean elimination half-life approximately 16 h
      at the MTD. Pharmacodynamic analyses demonstrated moderate correlation between
      plasma drug concentrations at 6 or 24 h and monoaster formation in peripheral
      blood mononuclear cells (PBMCs). CONCLUSIONS: AZD4877 is generally well-tolerated
      with pharmacodynamic evidence of target inhibition in circulating PBMCs.

PMID- 22615057
TI  - Phase I pharmacokinetic and pharmacodynamic study of cetuximab, irinotecan and
      sorafenib in advanced colorectal cancer.
AB  - Background This phase Ib study was designed to determine the maximum tolerated
      doses (MTD) and dose limiting toxicities (DLTs) of irinotecan and cetuximab with
      sorafenib. Secondary objectives included characterizing the pharmacokinetics and
      pharmacodynamics and evaluating preliminary antitumor activity in patients with
      advanced colorectal cancer (CRC). Methods Patients with metastatic, pretreated
      CRC were treated at five dose levels. Results Eighteen patients were recruited
      with median age 56.5 years. In the first five patients treated, 2 irinotecan
      related DLTs were observed. With reduced dose intensity irinotecan, there were no
      further DLTs. The most common toxicities were diarrhea, nausea/vomiting, fatigue,
      anorexia and rash. DLTs included neutropenia and thrombocytopenia. Two patients
      had partial responses (one with a KRAS mutation) and 8 had stable disease (8-36
      weeks). The median progression free survival (PFS) and overall survival (OS) were
      2.5 and 4.7 months respectively. Pharmacokinetic analyses suggest sorafenib and
      metabolite exposure correlate with OS and DLTs. Conclusions The recommended phase
      II dose (RP2D) is irinotecan 100 mg/m(2) i.v. days 1, 8; cetuximab 400 mg/m(2)
      i.v. days 1 and 250 mg/m(2) i.v. weekly; and sorafenib 400 mg orally twice daily
      in advanced, pretreated CRC. The combination resulted in a modest response rate.

PMID- 22615059
TI  - A phase I, dose-finding study of sunitinib combined with cisplatin and 5
      fluorouracil in patients with advanced gastric cancer.
AB  - Background This phase I, open-label, dose-escalation study examined the safety,
      maximum tolerated dose (MTD), and pharmacokinetics of sunitinib plus chemotherapy
      in patients with advanced gastric cancer. Patients and methods Sunitinib (25 or
      37.5 mg/day, Schedule 2/1: 2 weeks on treatment/1 week off) plus chemotherapy
      (fixed starting doses of cisplatin 80 mg/m(2) and 5-fluorouracil [5-FU] 4,000
      mg/m(2)) was administered to patients with advanced gastric cancer who had not
      received prior therapy for metastatic disease. Results Thirty-four patients were
      enrolled and received sunitinib 25 mg/day (n = 24) or 37.5 mg/day (n = 10) plus
      chemotherapy. No dose-limiting toxicity (DLT) was reported in the sunitinib 37.5
      mg cohort. However, repeated patterns of myelosuppression beyond the first cycle
      led to investigation of sunitinib 25 mg/day. This was the MTD, and one DLT (grade
      3 mucosal inflammation) was reported. The combination had an acceptable adverse
      event profile; generally of grade 1/2. There was no evidence of a pharmacokinetic
      drug-drug interaction between sunitinib and 5-FU. Six patients (26 %) receiving
      the MTD had a partial response and eight patients experienced stable disease >=3
      months. Conclusions Sunitinib plus cisplatin 80 mg/m(2) and 5-FU 4,000 mg/m(2)
      were combinable and adverse events were manageable. The MTD of sunitinib was
      established as 25 mg/day on Schedule 2/1.

PMID- 22615061
TI  - Pollen-mediated gene flow in wheat (Triticum aestivum L.) in a semiarid field
      environment in Spain.
AB  - Transgenic wheat (Triticum aestivum L.) varieties are being developed and field
      tested in various countries. Concerns regarding gene flow from genetically
      modified (GM) crops to non-GM crops have stimulated research to estimate
      outcrossing in wheat prior to the release and commercialization of any transgenic
      cultivars. The aim is to ensure that coexistence of all types of wheat with GM
      wheat is feasible in accordance with current regulations. The present study
      describes the result of a field experiment under the semi-arid climate conditions
      of Madrid, Spain, at two locations ("La Canaleja" and "El Encin" experimental
      stations) in Madrid over a 3-year period, from 2005 to 2007. The experimental
      design consisted of a 50 * 50 m wheat pollen source sown with wheat cultivars
      resistant to the herbicide chlortoluron ('Deganit' and 'Castan' respectively) and
      three susceptible receptor cultivars ('Abental', 'Altria' and 'Recital') sown in
      replicated 1 * 1 m plots at different distances (0, 1, 3, 5, 10, 20, 40, 80 and
      100 m) and four directions. Outcrossing rates were measured as a percentage of
      herbicide-resistant hybrids using an herbicide-screening assay. Outcrossing was
      greatest near the pollen source, averaging 0.029% at 0 m distance at "La
      Canaleja" and 0.337% at "El Encin", both below the 0.9% European Union regulated
      threshold, although a maximum outcrossing rate of 3.5% was detected in one
      recipient plot. These percentages declined rapidly as the distance increased, but
      hybrids were detected at different rates at distances of up to 100 m, the maximum
      distance of the experiment. Environmental conditions, as drought in 2004-2005 and
      2005-2006, may have influenced the extent of outcrossing. These assays carried
      out in wheat under semi-arid conditions in Europe provide a more complete
      assessment of pollen-mediated gene flow in this crop.

PMID- 22615060
TI  - Topophore C: a liposomal nanoparticle formulation of topotecan for treatment of
      ovarian cancer.
AB  - We have recently developed a liposomal nanoparticle (LNP) formulation of
      irinotecan based on loading method that involves formation of a complex between
      copper and the water soluble camptothecin. The loading methodology developed for
      irinotecan was evaluated to develop a LNP topotecan formulation (referred to
      herein as Topophore C) and test its activity in pre-clinical model of ovarian
      carcinoma. Topotecan was encapsulated into preformed liposomes containing 300 mM
      copper sulfate and the divalent metal ionophore A23187. Formulation optimization
      studies included assessments of loading efficiency, influence of temperature on
      drug loading and in vitro stability of the resulting formulation. In vivo
      assessments included drug and liposome pharmacokinetics, drug levels within
      plasma and the peritoneal cavity following intravenous (i.v.) administration in
      mice and efficacy studies on ES2 ovarian cancer model. Topotecan loading into
      liposomes was optimized with encapsulation efficiency of >98 % at a final drug-to
      lipid (D/L) mole ratio of 0.1. Higher D/L ratios could be achieved, but the
      resulting formulations were less stable as judged by in vitro drug release
      studies. Following Topophore C administration in mice the topotecan plasma half
      life and AUC were increased compared to free topotecan by 10-and 22-fold,
      respectively. Topophore C was 2-to 3-fold more toxic than free topotecan, however
      showed significantly better anti-tumor activity than free topotecan administered
      at doses with no observable toxic effects. Topophore C is a therapeutically
      interesting drug candidate and we are particularly interested in developing its
      use in combination with liposomal doxorubicin for treatment of platinum
      refractory ovarian cancer.

PMID- 22615062
TI  - Importance of OH(-) transport from cathodes in microbial fuel cells.
AB  - Cathodic limitation in microbial fuel cells (MFCs) is considered an important
      hurdle towards practical application as a bioenergy technology. The oxygen
      reduction reaction (ORR) needs to occur in MFCs under significantly different
      conditions compared to chemical fuel cells, including a neutral pH. The common
      reason cited for cathodic limitation is the difficulty in providing protons to
      the catalyst sites. Here, we show that it is not the availability of protons, but
      the transport of OH(-) from the catalyst layer to the bulk liquid that largely
      governs cathodic potential losses. OH(-) is a product of an ORR mechanism that
      has not been considered dominant before. The accumulation of OH(-) at the
      catalyst sites results in an increase in the local cathode pH, resulting in
      Nernstian concentration losses. For Pt-based gas-diffusion cathodes, using
      polarization curves developed in unbuffered and buffered solutions, we quantified
      this loss to be >0.3 V at a current density of 10 Am(-2) . We show that this loss
      can be partially overcome by replacing the Nafion binder used in the cathode
      catalyst layer with an anion-conducting binder and by providing additional buffer
      to the cathode catalyst directly in the form of CO(2) , which results in enhanced
      OH(-) transport. Our results provide a comprehensive analysis of cathodic
      limitations in MFCs and should allow researchers to develop and select materials
      for the construction of MFC cathodes and identify operational conditions that
      will help minimize Nernstian concentration losses due to pH gradients.

PMID- 22615064
TI  - [Resident training in ophthalmology: can the German system learn from the
      Malawian one?].
AB  - BACKGROUND: Training regulations in Germany and Malawi are compared. One German
      "Facharztausbildungsordnung" was compared with the syllabus of the Malawian
      Master of Medicine Degree in Ophthalmology. Germany nowadays has got 7000
      ophthalmologists, Malawi nine; population in Germany 80 million, in Malawi 14
      million. METHODS: We present a written comparison underlined with one
      illustrative table. RESULTS: Modalities in resident training are very different.
      Training period: Germany 60 months, Malawi 48 months. Training manner: In Germany
      mostly theoretical private studies at hospitals and in private practices.
      Practical advice comes from senior residents, specialists and consultants. It is
      qualitywise and quantitatively very different within the country. The Malawian
      syllabus is very structured according to teaching in theory and practice. There
      are 250 hours of regular teaching each year. Lecturers are especially paid for
      teaching from outside the country. Training aim in Germany is mainly a medical
      ophthalmologist whereas in Malawi it is an ophthalmic surgeon. Exams: Germans
      take part in an oral exam of 30 minutes after 60 months training. Malawian
      residents take exams every two years: written, oral, practical. Furthermore they
      are supposed to take part in exams of the ICO (International Council of
      Ophthalmology) - until now with 100% success for the first attempts. CONCLUSION:
      German residents have lots of academic freedom during their training. It is non
      uniform. Training aim in Germany is mainly a medical ophthalmologist whereas in
      Malawi it is an ophthalmic surgeon. The Malawian postgraduate training is uniform
      with scheduled instructions. That is why quality among candidates can be better
      compared.

PMID- 22615063
TI  - [Adapted and standardised patient management in the treatment of neovascular AMD
      in the outpatient setting of a university eye hospital].
AB  - Visual results in treating neovascular age-related macular degeneration (AMD)
      using intravitreal injected anti-VEGF (IVT) clearly depend on injection
      frequency. Regarding to the European approval Ranibizumab has to be used only in
      cases of recurrent visual loss after the loading phase. In contrast monthly
      treatment--as also provided in the ANCHOR and MARINA studies--is generally
      allowed in Switzerland. However, it is commonly tried to reduce the injection
      frequency because of the particular cost situation in all health systems and of
      cause also due to the necessary strict monitoring and reinjection regimes, which
      raise management problems with increasing patient numbers. In this article the
      special treatment regimes of our University Eye Hospital is presented, in which a
      reduced injection frequency basically leads to the same increased and stable
      visual results as in ANCHOR and MARINA; however, needing significantly more
      injections as generally provided in other countries of Europe. The main focus for
      achieving this in a large number of patients is placed on re-structuring our
      outpatient flow for IVT patients with particular emphasis on patient separation
      and standardisation of treatment steps leading to significantly reduced time
      consumption per patient. Measurements of timing and patient satisfaction before
      and after restructuring underline its importance in order to be able to treat
      more patients at a high quality even in the future. The exceptional importance of
      spectral domain OCT measurements as the most important criterium for indicating
      re-treatment is illustrated.

PMID- 22615065
TI  - Three-dimensional polycaprolactone scaffold-conjugated bone morphogenetic protein
      2 promotes cartilage regeneration from primary chondrocytes in vitro and in vivo
      without accelerated endochondral ossification.
AB  - As articular cartilage is avascular, and mature chondrocytes do not proliferate,
      cartilage lesions have a limited capacity for regeneration after severe damage.
      The treatment of such damage has been challenging due to the limited availability
      of autologous healthy cartilage and lengthy and expensive cell isolation and
      expansion procedures. Hence, the use of bone morphogenetic protein-2 (BMP-2), a
      potent regulator of chondrogenic expression, has received considerable attention
      in cartilage and osteochondral tissue engineering. However, the exact role of BMP
      2 in cartilage repair has been postulated to promote both cartilage formation and
      subsequent cartilage degradation through hypertrophy and endochondral
      ossification. Furthermore, it is likely that the manner in which BMP-2 is
      presented to chondrocytes will influence the physiologic pathway (repair vs.
      degeneration). This study investigates the relative influence of BMP-2 on
      cartilage matrix and potential subsequent bone matrix production using primary
      chondrocytes seeded on designed 3D polycaprolactone (PCL) scaffolds with
      chemically conjugated BMP-2. The results show that chemically conjugated BMP-2
      PCL scaffolds can promote significantly greater cartilage regeneration from
      seeded chondrocytes both in vitro and in vivo compared with untreated scaffolds.
      Furthermore, our results demonstrate that the conjugated BMP-2 does not
      particularly accelerate endochondral ossification even in a readily permissible
      and highly vascular in vivo environment compared with untreated PCL scaffolds.
      This study not only reveals the potential use of the BMP-2 conjugation delivery
      method for enhanced cartilage tissue formation but also gives new insights for
      the effects of conjugated BMP-2 on cartilage regeneration and osteochondral
      ossification.

PMID- 22615066
TI  - Beckwith-Wiedemann syndrome in sibs discordant for IC2 methylation.
AB  - Genetically heterogeneous imprinting disorders include Beckwith-Wiedemann
      syndrome (BWS) and multiple maternal hypomethylation syndrome (MMHS). Using DNA
      sequencing, quantitative PCR, SNuPE, pyrosequencing, and hybridization to the
      Illumina GoldenGate Methylation Cancer Panel 1 array, we characterized the
      genomic DNA of two brothers with BWS who were discordant for loss of methylation
      at several differentially methylated regions (DMR), including imprinting center 2
      (IC2) on chromosome band 11p15.5, which is often hypomethylated in BWS. In
      keeping with MMHS, the elder child had hypomethylation of SGCE and PLAGL1 as well
      as of IC2, whereas the younger brother demonstrated no loss of methylation at
      these DMRs. Although this discordance is consistent with the observation that 15
      20% of individuals with BWS do not have detectable genetic or epigenetic
      alterations of 11p15.5, this is the first report of familial recurrence of BWS
      with discordance for chromosomal 11p15.5 alterations. We hypothesize that this
      apparent discordance arises either from mosaicism precluding identification of
      IC2 hypomethylation in blood or buccal mucosa DNA of the younger child, or from
      hypomethylation at a site not interrogated by our molecular studies.

PMID- 22615067
TI  - Suggestive evidence of linkage identified at chromosomes 12q24 and 2p16 in
      African American prostate cancer families from Louisiana.
AB  - BACKGROUND: In the United States, incidence of prostate cancer in African
      American men is more than twice than that of any other race. Thus far, numerous
      disease susceptibility loci have been identified for this cancer but definite
      locus-specific information is not yet established due to the tremendous amount of
      genetic and disease heterogeneity; additionally, despite high prevalence of
      prostate cancer amongst African American men, this population has been under
      represented in genetic studies of prostate cancer. METHODS: In order to identify
      the susceptible locus (loci) for prostate cancer in African Americans, we have
      performed linkage analyses on members of 15 large high-risk families.
      Specifically, these families were recruited from Louisiana and represent a
      uniquely admixed African American population exclusive to Southern Louisiana. In
      addition to geographical constraints, these families were clinically homogeneous
      creating a well-characterized collection of large pedigrees. The families were
      genotyped with Illumina Infinium II SNP HumanLinkage-12 panel and extensive
      demographic and clinical information was documented from the hospital
      pathological reports and family interviews. RESULTS: We identified two novel
      regions, 12q24 and 2p16, with suggestive evidence of linkage under the dominant
      model of inheritance. CONCLUSIONS: This is the first time that chromosome 12q24
      (HLOD = 2.21) and 2p16 (HLOD = 1.97) has been shown to be associated with
      prostate cancer in high-risk African American families. These results provide
      insight to prostate cancer in an exceptional, well-characterized African American
      population, and illustrate the significance of utilizing large unique, but
      homogenous pedigrees.

PMID- 22615068
TI  - Evaluation of autopsy and police reports in the investigation of sudden
      unexplained death in the young.
AB  - To evaluate police and autopsy reports in sudden unexplained deaths in 0-40 year
      olds. A structured, blind review of police and autopsy reports send to a cardiac
      genetic service from before (February 2006-December 2007) and after (January
      December 2009) new best practice guidelines were introduced in Australia and New
      Zealand was performed. The reviews focused on reporting on: (1) presentation and
      clinical history, (2) cardiac autopsy, (3) histological tests and toxicology, and
      (4) detailed examination of coronary arteries. 110 reports were evaluated against
      the guidelines. 100 % reported location, 95 % activity at time of death, and 84 %
      some clinical history. Less than 25 % reported on family history,
      presence/absence of illicit drugs or alcohol, recorded a possible arrhythmic
      trigger, or history of fits/faints or collapses. Over 95 % listed heart weight,
      valvular examinations, pulmonary and some myocardial histology. Less than 50 %
      commented on septal, LV (left ventricle) and RV (right ventricle) wall thickness.
      Less than 50 % mentioned site of histology samples, or gave specific description
      of LV or RV histology or conduction system. Toxicology was not mentioned in a
      third. Histology of coronary arteries was described in only 18 %. Post guidelines
      reporting increased in some areas, e.g. in 1-40 year olds: antecedent symptoms
      (22-61 %), number and location of histology samples (0-47 %), and histology of
      coronary arteries (6-50 %). Most police and autopsy reports fall short of best
      practice guidelines. They have improved somewhat after the new guidelines were
      introduced, but need to be more consistent and particularly need to include
      significant negative findings.

PMID- 22615069
TI  - Routine CT scan combined with preliminary examination as a new method in
      determining the need for autopsy.
AB  - CT scanning is an intrinsic component of the workup of all admissions to the
      Victorian Institute of Forensic Medicine. Using a new system of preliminary
      examination a decision is made by the coroner as to whether or not an autopsy
      should occur following consultation with a forensic pathologist. This study
      examines 318 consecutive cases for the month of July 2010 where the deceased had
      a preliminary examination including a CT scan which was primarily interpreted by
      a forensic pathologist. Findings relate to the age and sex of the deceased, the
      value of CT scanning, pathologist variability in advising an autopsy examination
      as well as the input from our sessional radiologist. A breakdown of natural
      versus unnatural death is provided. Overall the process is effective in
      developing interaction between the medical and legal elements at the VIFM in
      efforts to process admissions in the most suitable manner.

PMID- 22615070
TI  - Impaired biomechanical properties correlate with neoangiogenesis as well as VEGF
      and MMP-3 expression during rat patellar tendon healing.
AB  - Recent studies reveal an important role of vascular endothelial growth factor
      (VEGF)-induced angiogenesis in degenerative tendon diseases. The way how VEGF
      influences mechanical properties of the tendons is not well understood yet. We
      here hypothesized that tendinopathy results in a hypoxia-mediated stimulation of
      VEGF and that the mechanical stability of the tendon is impaired in an angiogenic
      process by VEGF-induced matrix metalloproteinases (MMPs). A modified in situ
      freezing model of patellar tendon was used to create a tendinopathy. 0, 7, 14,
      and 28 days post-surgical animals were sacrificed and patellar tendons were
      dissected for biomechanical and immunohistochemical analysis. Native tendons were
      used as controls. Immunohistochemical staining revealed a peak in HIF-1alpha
      stabilization immediately after surgery. Both VEGF and MMP-3 were increased 7
      days after surgery. Angiogenesis was also abundant 7 days after surgery. In
      contrast, biomechanical stability of the tendon was decreased 7 days after
      surgery. The current results reveal a time-dependent correlation of HIF-1/VEGF
      induced and MMP-3-supported angiogenesis with decreased biomechanical properties
      during tendon healing. The therapeutical modulation of neoangiogenesis by
      influencing the level of VEGF and MMP-3 might be a promising target for new
      approaches in degenerative tendon diseases. 30:1952-1957, 2012.

PMID- 22615071
TI  - Mitochondria, calcium-dependent neuronal death and neurodegenerative disease.
AB  - Understanding the mechanisms of neuronal dysfunction and death represents a major
      frontier in contemporary medicine, involving the acute cell death in stroke, and
      the attrition of the major neurodegenerative diseases, including Parkinson's,
      Alzheimer's, Huntington's and Motoneuron diseases. A growing body of evidence
      implicates mitochondrial dysfunction as a key step in the pathogenesis of all
      these diseases, with the promise that mitochondrial processes represent valuable
      potential therapeutic targets. Each disease is characterised by the loss of a
      specific vulnerable population of cells--dopaminergic neurons in Parkinson's
      disease, spinal motoneurons in Motoneuron disease, for example. We discuss the
      possible roles of cell type-specific calcium signalling mechanisms in defining
      the pathological phenotype of each of these major diseases and review central
      mechanisms of calcium-dependent mitochondrial-mediated cell death.

PMID- 22615072
TI  - Tetrodotoxin blocks L-type Ca2+ channels in canine ventricular cardiomyocytes.
AB  - Tetrodotoxin (TTX) is believed to be the most selective inhibitor of voltage
      gated fast Na(+) channels in excitable tissues, including nerve, skeletal muscle,
      and heart, although TTX sensitivity of the latter is lower than the former by at
      least three orders of magnitude. In the present study, the TTX sensitivity of L
      type Ca(2+) current (I (Ca)) was studied in isolated canine ventricular cells
      using conventional voltage clamp and action potential voltage clamp techniques.
      TTX was found to block I (Ca) in a reversible manner without altering
      inactivation kinetics of I (Ca). Fitting results to the Hill equation, an IC(50)
      value of 55 +/- 2 MUM was obtained with a Hill coefficient of unity (1.0 +/-
      s0.04). The current was fully abolished by 1 MUM nisoldipine, indicating that it
      was really I (Ca). Under action potential voltage clamp conditions, the TTX
      sensitive current displayed the typical fingerprint of I (Ca), which was absent
      in the presence of nisoldipine. Stick-and-ball models for Cav1.2 and Nav1.5
      channel proteins were constructed to explain the differences observed between
      action of TTX on cardiac I (Ca) and I (Na). This is the first report
      demonstrating TTX to interact with L-type calcium current in the heart.

PMID- 22615073
TI  - AS1411 aptamer tagged PLGA-lecithin-PEG nanoparticles for tumor cell targeting
      and drug delivery.
AB  - Liposomes and polymers are widely used drug carriers for controlled release since
      they offer many advantages like increased treatment effectiveness, reduced
      toxicity and are of biodegradable nature. In this work, anticancer drug-loaded
      PLGA-lecithin-PEG nanoparticles (NPs) were synthesized and were functionalized
      with AS1411 anti-nucleolin aptamers for site-specific targeting against tumor
      cells which over expresses nucleolin receptors. The particles were characterized
      by transmission electron microscope (TEM) and X-ray photoelectron spectroscopy
      (XPS). The drug-loading efficiency, encapsulation efficiency and in vitro drug
      release studies were conducted using UV spectroscopy. Cytotoxicity studies were
      carried out in two different cancer cell lines, MCF-7 and GI-1 cells and two
      different normal cells, L929 cells and HMEC cells. Confocal microscopy and
      flowcytometry confirmed the cellular uptake of particles and targeted drug
      delivery. The morphology analysis of the NPs proved that the particles were
      smooth and spherical in shape with a size ranging from 60 to 110 nm. Drug-loading
      studies indicated that under the same drug loading, the aptamer-targeted NPs show
      enhanced cancer killing effect compared to the corresponding non-targeted NPs. In
      addition, the PLGA-lecithin-PEG NPs exhibited high encapsulation efficiency and
      superior sustained drug release than the drug loaded in plain PLGA NPs. The
      results confirmed that AS1411 aptamer-PLGA-lecithin-PEG NPs are potential carrier
      candidates for differential targeted drug delivery.

PMID- 22615074
TI  - Incretin therapies in the management of patients with type 2 diabetes mellitus
      and renal impairment.
AB  - Renal impairment (RI) is common among patients with type 2 diabetes mellitus
      (T2DM), and these patients also experience an age-related decline in renal
      function. At the same time, treatment options are more limited and treatment is
      more complex, particularly in patients with moderate or severe RI due to
      contraindications, need for dose adjustment and/or regular monitoring, and side
      effects, such as fluid retention and hypoglycemia, which are a more serious
      concern in this patient population. Incretin therapies, consisting of the
      injectable glucagon-like peptide-1 (GLP-1) receptor agonists and the oral
      dipeptidyl peptidase-4 (DPP-4) inhibitors, are a promising new class of
      antihyperglycemic drugs. In the overall population, they improve glycemic control
      in a glucose-dependent manner and are not likely to cause hypoglycemia,
      representing a clear advantage in at-risk populations. Data regarding use of
      these agents in renally impaired patients have started to emerge, and the
      objective of this article is to provide an overview of the currently available
      data and the potential role of these novel agents in the management of patients
      with T2DM and RI. Data for the GLP-1 receptor agonists in patients with moderate
      or severe RI are still limited, with no trials dedicated to these populations
      currently published. In addition, their potential to cause gastrointestinal side
      effects may limit use in patients with RI due to the risk of dehydration and
      hypovolemia. The use of GLP-1 receptor agonists in patients with moderate or
      severe RI is therefore, at present, underlying caution and/or restrictions. On
      the other hand, data from specific trials in patients with moderate or severe RI
      are now becoming available for most of the DPP-4 inhibitors. These studies
      demonstrate good efficacy and tolerability of the DPP-4 inhibitors in patients
      with moderate or severe RI, thus opening a place for these therapies in the
      treatment of populations with T2DM and RI. Several of the DPP-4 inhibitors are
      already approved for use in patients with moderate or severe RI, including for
      those with end-stage renal disease. While discussing the advantages related to
      their common mechanism of action, this article also describes differences among
      the DPP-4 inhibitors (eg, related to their pharmacokinetic properties and the
      available clinical data). In conclusion, while initial data for these new
      therapies are promising, further experience is needed to fully assess the risk
      benefit balance and clinical positioning of these agents in RI populations.

PMID- 22615076
TI  - The diabetes paradox: diabetes is not independently associated with mortality in
      critically ill patients.
AB  - Intensive monitoring of blood glucose levels and treatment of hyperglycemia in
      critically ill patients has become a standard of care over the past decade.
      Although diabetes is associated with a large burden of illness in outpatients,
      the "diabetes paradox" suggests that in patients admitted to intensive care
      units, the presence of diabetes as a comorbidity is not independently associated
      with increased risk of mortality. This review article 1) describes prospective
      trial and observational cohort literature addressing this issue, 2) addresses the
      potential mechanisms underlying the diabetes paradox, and 3) discusses
      implications for patient care and future research.

PMID- 22615075
TI  - Diabetes and stress hyperglycemia in the intensive care unit: outcomes after
      cardiac surgery.
AB  - BACKGROUND: Hyperglycemia is common in the post-cardiac surgery population and
      has been associated with increased mortality rates, surgical length of stay, and
      infection rates. Although hospitalized patients with diabetes are known to have
      more complications, recent studies in various hospital settings have reported
      worse outcomes in patients with stress hyperglycemia than in those with diabetes.
      AIM: The primary objective of this study was to analyze 30- and 90-day mortality
      rates in post-cardiac surgery patients with stress hyperglycemia and diabetes who
      were managed to achieve similar moderate blood glucose goals using the University
      of Michigan Hospital (Ann Arbor, MI) insulin protocol between 2005 and 2008. The
      secondary outcomes were rates of postoperative complications, including
      hypoglycemia. METHODS: A standardized glucose management program was followed to
      treat all patients in the cardiac intensive care unit, with a blood glucose goal
      of 100 to 140 mg/dL. Data from 1973 patients with either diabetes or stress
      hyperglycemia were analyzed to identify associations between mean postoperative
      blood glucose levels and mortality, incidence of hypoglycemia, and complication
      rates. RESULTS: Mortality rates did not differ between patients with diabetes and
      stress hyperglycemia (3.4 and 2.3%; P = 0.2). Rates of severe hypoglycemia were
      low (1%) for both groups and were not associated with an increase in mortality (P
      = 0.95). Other complication rates were similar between patients with diabetes and
      stress hyperglycemia. CONCLUSION: Maintaining a blood glucose range between 100
      to 140 mg/dL in post-cardiac surgery patients was associated with a low mortality
      rate, low risk of hypoglycemia, and with complications rates that were similar in
      patients with diabetes and stress hyperglycemia.

PMID- 22615077
TI  - Obstacles to optimal management of inpatient hyperglycemia in noncritically ill
      patients.
AB  - Compelling evidence continues to evolve linking hyperglycemia in hospitalized
      patients with adverse clinical outcomes. In 2012, The Endocrine Society's
      clinical practice guidelines for management of hyperglycemia in non-critical care
      settings were published, and explicit blood glucose targets for noncritically ill
      patients were recommended. These matched those set by the American Diabetes
      Association (ADA) in the Standards of Medical Care in Diabetes--2012. Although
      there are more specific targets for achieving optimal glycemic control in
      critically ill and noncritically ill inpatients, implementing standardized
      processes to achieve these goals continues to remain a challenge. This article
      summarizes these obstacles and emphasizes the quality of care and safety issues
      (eg, hypoglycemia and insulin errors) that are associated with the management of
      hyperglycemia in hospitalized patients. The use of intravenous insulin via
      computerized or manual standardized protocols in critically ill patients has been
      shown to be effective in achieving glucose control; we focus on the barriers to
      the appropriate use of subcutaneous insulin in hospitalized patients with
      noncritical illness. We also elaborate on how to overcome most of these obstacles
      and the clinical inertia to treat hyperglycemia through focused education and
      surveillance, and then "re-education," using a multidisciplinary, collaborative
      approach. Transition from intravenous insulin to subcutaneous insulin, and
      transition from an inpatient to an outpatient glycemic regimen at the time of
      discharge, are identified as aspects of management that require extra attention.
      We also emphasize the need for a multidisciplinary task force responsible for
      monitoring and enhancing glycemic control practices in the hospital on an ongoing
      basis.

PMID- 22615078
TI  - Glycemic management in the inpatient setting.
AB  - Hyperglycemia occurs frequently in hospitalized patients and affects patient
      outcomes, including mortality, inpatient complications, hospital length of stay,
      and overall hospital costs. Various degrees of glycemic control have been studied
      and consensus statements from the American Diabetes Association/American
      Association of Clinical Endocrinologists and The Endocrine Society recommend a
      target blood glucose range of 140 to 180 mg/dL in most hospitalized patients.
      Insulin is the preferred modality for treating all hospitalized patients with
      hyperglycemia, as it is adaptable to changing patient physiology over the course
      of hospitalization. Critically ill patients should receive intravenous insulin
      infusion, and all noncritically ill patients with hyperglycemia (individuals with
      and without diabetes) should be managed using a subcutaneous insulin algorithm
      with basal, nutritional, and correctional dose components. Hypoglycemia remains a
      limiting factor to achieving optimal glycemic targets. Similar to hyperglycemia,
      hypoglycemia is an independent risk factor for poor outcomes in hospitalized
      patients. Improvement in glycemic control throughout the hospital includes
      efforts from all health care providers. Institutions can encourage safe insulin
      use by using insulin algorithms, preprinted order sets, and hypoglycemia
      protocols, as well as by supporting patient and health care provider education.

PMID- 22615079
TI  - Antidiabetic properties of berberine: from cellular pharmacology to clinical
      effects.
AB  - Berberine is an alkaloid that is highly concentrated in the roots, rhizomes, and
      stem bark of various plants. It affects glucose metabolism, increasing insulin
      secretion, stimulating glycolysis, suppressing adipogenesis, inhibiting
      mitochondrial function, activating the 5' adenosine monophosphate-activated
      protein kinase (AMPK) pathway, and increasing glycokinase activity. Berberine
      also increases glucose transporter-4 (GLUT-4) and glucagon-like peptide-1 (GLP-1)
      levels. On GLP-1 receptor activation, adenylyl cyclase is activated, and cyclic
      adenosine monophosphate is generated, leading to activation of second messenger
      pathways and closure of adenosine triphosphate-dependent potassium channels.
      Increased intracellular potassium causes depolarization, and calcium influx
      through the voltage-dependent calcium channels occurs. This intracellular calcium
      increase stimulates the migration and exocytosis of the insulin granules. In
      glucose-consuming tissues, such as adipose, or liver or muscle cells, berberine
      affects both GLUT-4 and retinol-binding protein-4 in favor of glucose uptake into
      cells; stimulates glycolysis by AMPK activation; and has effects on the
      peroxisome proliferator-activated receptor gamma molecular targets and on the
      phosphorylation of insulin receptor substrate-1, finally resulting in decreased
      insulin resistance. Moreover, recent studies suggest that berberine could have a
      direct action on carbohydrate metabolism in the intestine. The antidiabetic and
      insulin-sensitizing effect of berberine has also been confirmed in a few
      relatively small, short-term clinical trials. The tolerability is high for low
      dosages, with some gastrointestinal complaints appearing to be associated with
      use of high dosages.

PMID- 22615080
TI  - Screening for diabetic retinopathy: review of current methods.
AB  - OBJECTIVE: To review the current screening methods for diabetic retinopathy, with
      a focus on nonmydriatic digital fundus photography. METHODS: Articles from
      Medline were reviewed from 1976 to November 2011 for different combinations of
      the words "diabetic retinopathy," "screening," "fundus photography," and
      "nonmydriasis." RESULTS: Because of its ease of use and cost-effectiveness,
      digital fundus photography is becoming the preferred method for diagnosing
      diabetic retinopathy. Current research has proven that pupillary dilation is not
      a necessary step in the fundus examination, although it reduces the number of
      unnecessary referrals to ophthalmologists. Automated grading systems, while
      saving time and reducing human error, still need refinement before they can
      replace manual grading by trained ophthalmologists. CONCLUSION: Nonmydriatic
      digital fundus photography with manual grading by a trained technician is an
      acceptable method of screening for diabetic retinopathy.

PMID- 22615081
TI  - The role of point-of-care beta-hydroxybutyrate testing in the diagnosis of
      diabetic ketoacidosis: a review.
AB  - The number of patients with diabetes and diabetes-related complications is
      increasing. Rapid and accurate diagnosis is key to efficiently providing the
      appropriate level of care for patients with diabetes. When faced with a
      hyperglycemic patient (ie, blood glucose level > 250 mg/dL), the prevailing
      attitude among health care providers is to "think worst first," and common
      clinical practice is to perform an evaluation for diabetic ketoacidosis (DKA).
      Traditionally, diagnosing DKA in accordance with the American Diabetes
      Association guidelines requires performing >= 2 (possibly 3) tests to obtain
      measurements for blood glucose, serum bicarbonate, serum pH, and serum anion gap
      levels, as well as measurements of either urine or serum ketone bodies. Recently,
      commercial point-of-care beta-hydroxybutyrate measurement devices have become
      readily accessible and less expensive. These devices offer the potential to
      simplify clinicians' diagnostic approach to hyperglycemic patients. In this
      evidence-based literature review, we describe the use of point-of-care beta
      hydroxybutyrate testing for diagnosing DKA, and discuss its limitations in
      determining DKA severity.

PMID- 22615082
TI  - Preventing venous thromboembolic events after total hip arthroplasty: new
      developments in clinical practice.
AB  - Total hip arthroplasty is a frequently performed orthopedic surgical procedure,
      and the number of these surgeries is expected to increase significantly over the
      coming years. Patients undergoing joint arthroplasty are at a particularly high
      risk for developing venous thromboembolic events (eg, deep vein thrombosis and
      pulmonary embolism). Prevention of postoperative complications is an important
      responsibility not only for orthopedic surgeons, but also for other clinicians
      involved in patients' care. Effective thromboprophylaxis is crucial to reduce the
      risk of developing venous thromboembolism following total hip arthroplasty and is
      an important goal of therapy. In response to some of the practical limitations of
      traditional anticoagulants, a new generation of oral anticoagulants has been
      developed. These agents include the selective factor Xa inhibitors, rivaroxaban
      and apixaban, and the direct thrombin inhibitor dabigatran etexilate. The
      objective of this review article is to update hospitalists on the trial data and
      clinical considerations surrounding the new anticoagulants. Hospitalists play a
      key role in caring for surgical patients either in a consultative role or in
      conjunction with surgical teams. Thus, a practical knowledge of recent
      developments in thromboprophylaxis is essential for providing high-quality,
      evidence-based care.

PMID- 22615083
TI  - A cohort study investigating compliance with guidelines for platelet count
      monitoring during heparin thromboprophylaxis.
AB  - BACKGROUND: Heparin is the most common agent used for prevention of venous
      thromboembolism. To promote early detection of heparin-induced thrombocytopenia,
      guidelines recommend episodic platelet count monitoring for specified patient
      populations. However, physician compliance with these guidelines has never been
      reported for patients receiving heparin for pharmacologic prophylaxis. AIM: The
      aim of this study was to evaluate the frequency of and factors associated with
      physician failure to monitor patient platelet counts. RESULTS: We conducted a
      retrospective cohort study of 2350 admissions of patients aged >= 18 years who
      received >= 4 consecutive days of prophylactic heparin. There was nonadherence to
      monitoring recommendations in 659 (28%) patients. Monitoring was not more likely
      among patients for whom monitoring was recommended compared with patients for
      whom no monitoring was recommended (31% vs 27%; adjusted hazard ratio, 0.9; 95%
      CI, 0.7-1.1). Compared with patients admitted to the general medicine service,
      monitoring was significantly less common among patients admitted to orthopedic
      surgery or obstetric-gynecologic services (adjusted hazard ratio, 1.6; 95% CI,
      1.1-2.2 and adjusted hazard ratio, 2.4; 95% CI, 1.8-3.2, respectively). A
      decrease in platelet count (>= 50%) was detected in 90 (4%) patients, but in only
      12 (11%) patients was heparin stopped, and in only 11 (12%) patients were heparin
      induced thrombocytopenia antibody levels obtained. Of the 11 patients for whom
      heparin-induced thrombocytopenia antibody levels were obtained, 6 (0.26% of the
      patient population) were positive. CONCLUSION: We found that compliance by
      physicians with platelet count monitoring recommendations was poor for patients
      who had received heparin for venous thromboembolism prophylaxis, and platelet
      count monitoring appeared to be unrelated to American College of Chest Physicians
      recommendations for routine monitoring. Compliance was particularly poor in
      orthopedic surgery and obstetric-gynecologic services.

PMID- 22615084
TI  - Bleeding complications in patients with acute coronary syndromes: are they
      important and how can we prevent them?
AB  - Progress in antithrombotic medications and revascularization procedures has
      helped to reduce mortality in patients with acute coronary syndromes (ACS).
      However, these therapies can significantly increase the risk of bleeding.
      Bleeding complications are important clinical outcomes in patients with ACS. Data
      from numerous randomized controlled trials and large registries have demonstrated
      that bleeding is independently associated with a significantly higher risk of
      mortality in patients with ACS. Furthermore, bleeding complications are
      associated with an increased risk of recurrent ischemic events. The challenge of
      preventing bleeding complications while obtaining the optimal antithrombotic
      benefits of ACS management requires careful consideration of factors associated
      with patients, pharmacotherapy, and interventional procedures. Clinicians should
      be able to risk stratify patients for bleeding events just as they would do for
      recurrent ischemic events in ACS.

PMID- 22615085
TI  - Latest evidence in personalized antiplatelet therapy in patients with acute
      coronary syndromes undergoing percutaneous coronary intervention.
AB  - In patients with acute coronary syndromes undergoing percutaneous coronary
      intervention, the combination of aspirin and clopidogrel, a P2Y12 adenosine
      diphosphate (ADP) receptor antagonist, is the gold standard of antiplatelet
      therapy. Two more potent P2Y12 ADP receptor antagonists are now available.
      Pharmacodynamic studies have revealed a large interindividual variability in the
      biological response to clopidogrel that is primarily related to variable active
      metabolite generation, depending on clinical factors, drug-drug interactions, and
      genetic polymorphisms. Several assays to measure platelet function are available
      and have revealed a high prevalence of high on-treatment platelet reactivity
      (HTPR). Patients exhibiting HTPR after a clopidogrel loading dose have a higher
      risk of thrombotic recurrence after percutaneous coronary intervention. A recent
      consensus has defined HTPR for the main platelet assays available (using receiver
      operating characteristic curve analysis) to define the optimal cutoff value for
      each assay in order to predict thrombotic recurrences. In this article, we
      present several lines of evidence that suggest a therapeutic window of platelet
      reactivity inhibition with P2Y12 ADP receptor antagonists. Such a paradigm shift
      is supported by the results of the Platelet Inhibition and Patient Outcomes
      (PLATO) trial and the Trial to Assess Improvement in Therapeutic Outcomes by
      Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial
      Infarction (TRITON-TIMI) 38, which showed the superiority of ticagrelor and
      prasugrel on thrombotic events compared with clopidogrel; however, these 2
      medications had an increased bleeding rate. With the results of these trials, in
      addition to the evidence of a therapeutic window with P2Y12 ADP receptor
      antagonists, we summarize the potential of platelet reactivity monitoring and
      pharmacogenomics to tailor therapy.

PMID- 22615086
TI  - Perioperative antiplatelet management in patients with coronary artery stenting.
AB  - Coronary artery disease is the primary cause of mortality in men and women in the
      United States. Transcatheter coronary intervention is the mainstay of treatment
      for patients with acute coronary artery disease presentations and patients with
      stable disease. Although percutaneous intervention initially only included
      balloon angioplasty, it now typically involves the placement of intracoronary
      stents. To overcome the limitations of bare-metal stents, namely in-stent
      restenosis, stents have been developed that remove pharmaceuticals that reduce
      neointimal hyperplasia and in-stent restenosis. However, these pharmaceutical
      agents also delay stent endothelialization, posing a prolonged risk of in situ
      thrombosis. Placement of an intracoronary stent (eg, bare-metal or drug-eluting
      stent) requires dual antiplatelet therapy to prevent the potentially life
      threatening complication of stent thrombosis. The optimal duration of dual
      antiplatelet therapy following stent placement is unknown. This article discusses
      the factors to be considered when deciding when dual antiplatelet therapy can be
      safely discontinued. Unfortunately, in the hospital setting, this decision to
      interrupt dual antiplatelet therapy frequently must be made shortly after stent
      placement because of unanticipated surgical procedures or other unforeseen
      complications. The decision of when dual antiplatelet therapy can be safely
      interrupted needs to be individualized for each patient and involves factoring in
      the type of stent; the location and complexity of the lesion stented; post-stent
      lesion characteristics; the amount of time since stent placement; and the
      antiplatelet regimen currently in use, along with its implication for bleeding
      during the proposed procedure. Having a protocol in place, such as the protocol
      described in this article, can help guide this decision-making process and avoid
      confusion and potential error.

PMID- 22615087
TI  - Patient management, and time and health care resource utilization associated with
      the use of intravenous bisphosphonates for patients with metastatic bone disease:
      a Delphi study.
AB  - OBJECTIVE: To identify patient management patterns in patients with solid tumors
      and metastatic bone disease who are receiving intravenous (IV) bisphosphonates
      (zoledronic acid and pamidronate), and to estimate the time and health care
      resources used for preparation and administration of zoledronic acid and
      pamidronate in patients with metastatic bone disease in Canada. METHODS: A
      modified 2-round Delphi technique was used, which was composed of 7 clinical
      experts. The first round was performed through telephone interviews with
      individual clinical experts to assess the management of patients with bone
      metastases receiving IV zoledronic acid and pamidronate. The interviews focused
      on qualitative issues, such as drugs administered, cancers identified, and the
      method of drug administration. The information obtained from the first round was
      used to describe typical patient management patterns. The information obtained
      from the second round was done by a face-to-face meeting involving all expert
      members, with the aim of confirming the management patterns, and identifying
      commonality and uniqueness across institutions. The time and health care
      resources needed for preparation and administration of the IV bisphosphonates
      were estimated. RESULTS: The expert panel comprised 4 pharmacists and 3 nurses
      from 2 centers in Ontario and 3 centers in Quebec. The main stages identified,
      which were associated with the preparation and administration of pamidronate and
      zoledronic acid, included preinfusion activities, IV access set-up, IV
      bisphosphonate preparation, chemotherapy infusion (if applicable), IV
      bisphosphonate infusion, and postinfusion activities. Five patient management
      patterns were identified and varied with respect to inclusion of chemotherapy and
      the use of ambulatory infusion devices. Without chemotherapy, the mean time for
      preparation and administration of zoledronic acid ranged from 38 minutes in a
      community service center to 85 minutes in a hospital-based cancer center. With
      chemotherapy, the total mean time increased to 119 minutes for patients with
      prostate cancer and 173 minutes for patients with breast cancer. The mean time
      for preparation and administration of pamidronate was 159 minutes with the use of
      a regular infusion device, and the time in the clinic was only 14 minutes with
      the use of an ambulatory infusion device. If chemotherapy was scheduled on the
      same visits, the mean time increased substantially, and varied depending on the
      type of cancer being treated. CONCLUSION: Preparation and administration of IV
      bisphosphonates are associated with notable burden to health care providers and
      patients, even if the waiting time, including preinfusion (eg, IV access set-up,
      serum creatinine level monitoring) and postinfusion activities, were excluded.
      Variations in the time and health care resources utilized for preparing and
      administering IV bisphosphonates were observed across the centers in Canada. The
      variation could be primarily due to the difference in patient management
      patterns.

PMID- 22615088
TI  - A medical resident post-discharge phone call study.
AB  - BACKGROUND: Several studies have identified the post-discharge period as a time
      of vulnerability for patients, and an opportunity exists to improve patient care.
      Adverse drug events are the most common events leading to complications during
      the post-discharge period. Recent studies have shown that using a scripted
      medication reconciliation process improves the quality of patient care.
      OBJECTIVE: Does a phone call from a medical resident within 72 hours after
      hospital discharge improve patient satisfaction and quality of care? Does this
      exercise result in improved attitudes and competence for practice-based learning,
      and improvement and system-based practice of participating residents? MATERIALS
      AND METHODS: This was a prospective randomized study comparing 1 group of
      patients that received a medication reconciliation phone call from a medical
      resident within 72 hours after discharge with a control group that did not
      receive a call. Adult patients aged >= 18 years on a medical resident service for
      >= 2 days and being discharged to home were invited to participate. The primary
      endpoint of the study was patient satisfaction. Secondary endpoints included
      readmission rates, emergency department visits, follow-up with the primary care
      provider, and resident attitudes and competence. RESULTS: The primary and
      secondary endpoints did not reach statistical significance. However, a medication
      reconciliation error occurred in 48% of patients, and 93% of residents agreed
      that the phone call was beneficial to patient care. CONCLUSION: Although patient
      satisfaction was not improved from this exercise, a follow-up call to patients
      after hospital discharge can identify otherwise missed medication reconciliation
      errors. Medical residents found the phone call to be worthwhile and gained
      valuable insight into their own discharge practices as demonstrated by self
      reflection and intended change in discharge practices.

PMID- 22615089
TI  - Evaluating the adequacy of fluid resuscitation in patients with septic shock:
      controversies and future directions.
AB  - Fluid resuscitation is a cornerstone in the treatment of severe sepsis and septic
      shock. However, there is little evidence to guide clinicians in its
      administration. Current guidelines recommend targeting fluid therapy based on
      measurements of cardiac filling pressures, such as central venous pressure.
      Static pressures are poor predictors of a patient's response to fluid. Such
      response can be better predicted by measuring changes in hemodynamic parameters
      caused by positive pressure ventilation or maneuvers designed to simulate
      increased preload. These changes can be measured by analysis of arterial
      waveforms, echocardiography or Doppler, or with emerging noninvasive
      technologies. This article reviews the current role of fluid replacement
      strategies and the use of monitoring systems in the overall resuscitation of
      patients with severe sepsis and septic shock.

PMID- 22615091
TI  - Ventilator-associated pneumonia: a comprehensive review.
AB  - Ventilator-associated pneumonia (VAP) is the most frequent and severe infection
      acquired in the intensive care unit, leading to prolonged mechanical ventilation
      and excess mortality. This article reviews the different aspects of VAP, such as
      risk factors, causative agents, and approaches to diagnosis, treatment, and
      prevention. Several aspects of VAP are still considered controversial.

PMID- 22615090
TI  - Evaluation of the IDSA/ATS minor criteria for severe community-acquired
      pneumonia.
AB  - INTRODUCTION: Our aim was to evaluate the minor criteria recommended by the 2007
      Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) as
      predictors of 30-day mortality, the need for invasive mechanical ventilation,
      and/or the need for vasopressor support as markers of severity in patients
      hospitalized with community-acquired pneumonia (CAP). METHODS: Patients admitted
      to 2 academic teaching hospitals over a 4-year period (January 1, 1999 to
      December 1, 2002) were identified as having CAP. We used modified minor criteria
      established by the 2007 IDSA/ATS guidelines. The primary outcome measure was 30
      day mortality, and the secondary outcome measures were need for invasive
      mechanical ventilation and/or need for vasopressor support. RESULTS: About half
      of the patients in the cohort (n = 352/787 [46%]) had >= 1 minor criterion, but
      only 128 (16.3%) had >= 3 minor criteria present at hospital admission. In the
      multivariable analysis, hypoxemia, multilobar infiltrates, and leukopenia were
      associated with 30-day mortality (P < 0.05). In addition, hypoxemia and
      confusion/disorientation were associated with the need for invasive mechanical
      ventilation and/or vasopressor support (P < 0.05). The presence of >= 3 minor
      criteria was associated with 30-day mortality (odds ratio, 4.82), and the need
      for invasive mechanical ventilation and/or vasopressor support (odds ratio,
      2.59). CONCLUSION: Our results show that hypoxemia, multilobar infiltrates, and
      leukopenia were the most predictive minor criteria for 30-day mortality. In
      contrast, hypoxemia and confusion/disorientation were the 2 individual minor
      severe criteria that were more likely to require invasive mechanical ventilation
      and/or vasopressor support. At least 3 2007 IDSA/ATS minor severe criteria were
      associated with 30-day mortality and need for invasive mechanical ventilation
      and/or vasopressor support.

PMID- 22615092
TI  - A review of epidural catheter-related infections.
AB  - Spinal drug delivery is a generally safe and effective therapy for the treatment
      of both acute and chronic pain. However, it can be occasionally associated with
      significant complications, including neurologic injury, as a result of bleeding
      and infection in a confined space. This article focuses on risk factors for
      developing epidural catheter-related infections as well as strategies to minimize
      risks. Additionally, the diagnosis and management of epidural catheter-related
      infections, both superficial and deep, are discussed.

PMID- 22615093
TI  - Fabrication and characterization of three-dimensional electrospun scaffolds for
      bone tissue engineering.
AB  - When traumatic injury, tumor removal, or disease results in significant bone
      loss, reconstructive surgery is required. Bone grafts are used in orthopedic
      reconstructive procedures to provide mechanical support and promote bone
      regeneration. In this study, we applied a heat sintering technique to fabricate
      3D electrospun scaffolds that were used to evaluate effects of mineralization and
      fiber orientation on scaffold strength. We electrospun PLLA/gelatin scaffolds
      with a layer of PDLA and heat sintered them into three-dimensional cylindrical
      scaffolds. Scaffolds were mineralized by incubation in 10* simulated body fluid
      for 6, 24, and 48 h to evaluate the effect of mineralization on scaffolds
      compressive mechanical properties. The effects of heat sintering hydroxyapatite
      (HA) microparticles directly to the scaffolds on mineral deposition, distribution
      and mechanical properties of the scaffolds were also evaluated. We found that
      orientation of the fibers had little effect on the compressive mechanical
      properties of the scaffolds. However, increasing the mineralization times
      resulted in an increase in compressive mechanical properties. Also, the direct
      addition of HA microparticles had no effect on the scaffold mechanical
      properties, but had a significant effect on the mineral deposition on
      PLLA/gelatin scaffolds.

PMID- 22615094
TI  - CYTOMETRY 2012--what would Ehrlich do?

PMID- 22615099
TI  - The diversity of techniques to study electrochemically active biofilms highlights
      the need for standardization.
AB  - Microbial bioelectrochemical systems (BESs) employ whole microorganisms to
      catalyze electrode reactions. BESs allow electricity generation from wastewater,
      electricity-driven (bio)production, biosensing, and bioremediation. Many of these
      processes are perceived as highly promising; however, to date the performance of
      particularly bioproduction processes is not yet at the level required for
      practical applications. Critical to enabling high catalytic activity are the
      electrochemically active microorganisms. Whether the biocatalyst comes as a
      planktonic cell, a surface monolayer of cells, or a fully developed biofilm,
      effective electron transfer and process performance need to be achieved. However,
      despite many different approaches and extensive research, many questions
      regarding the functioning of electroactive microorganisms remain open. This is
      certainly due to the complexity of bioelectrochemical processes, as they depend
      on microbial, electrochemical, physical-chemical, and operational considerations.
      This versatility and complexity calls for a plethora of analytical tools required
      to study electrochemically active microorganisms, especially biofilms. Here, we
      present an overview of the parameters defining electroactive microbial biofilms
      (EABfs) and the analytical toolbox available to study them at different levels of
      resolution. As we will show, a broad diversity of techniques have been applied to
      this field; however, these have often led to conflicting information.
      Consequently, to alleviate this and further mature the field of BES research, a
      standardized framework appears essential.

PMID- 22615100
TI  - Looking at and listening to cancer cells.

PMID- 22615101
TI  - Reactive half-metallocenium ionic liquids that undergo solventless ligand
      exchange.
AB  - The piano-stool half-metallocenium cations [Fe(C(5)R(5))(CO)(2)L](+) (C(5)R(5) =
      C(5)H(5), C(5)Me(5), C(5)Me(4)Et; L = 1-pentene, nBuCN, MeCN, Me(2)S, NH(3),
      NMe(3), pyridine) provide ionic liquids (ILs) with the
      bis(trifluoromethanesulfonyl)imide (Tf(2)N) anion without introducing long alkyl
      chains. Their melting points are affected by molecular symmetry, and their
      thermal stabilities reflect the strength of the metal-ligand bonding. These are
      reactive liquids that show solventless ligand exchange reactions by gas
      absorption. The direction of the ligand-exchange reaction is correlated with the
      stabilities. Based on the variation of the melting points, these ILs undergo
      transformations between the liquid and solid phases associated with the reaction.

PMID- 22615102
TI  - Mantle cell lymphoma: 2012 update on diagnosis, risk-stratification, and clinical
      management.
AB  - DISEASE OVERVIEW: Mantle cell lymphoma (MCL) is a non-Hodgkin lymphoma
      characterized by involvement of the lymph nodes, spleen, blood, and bone marrow
      with a short remission duration to standard therapies and a median overall
      survival of 4-5 years. DIAGNOSIS: Diagnosis is based on lymph node, bone marrow,
      or tissue morphology of centrocytic lymphocytes, small cell type, or blastoid
      variant cells. A chromosomal translocation t(11:14) is the molecular hallmark of
      MCL, resulting in the overexpression of cyclin D1. Cyclin D1 is detected by
      immunohistochemistry in 98% of cases. The absence of SOX-11 or a low Ki-67 may
      correlate with a more indolent form of MCL. The differential diagnosis of MCL
      includes small lymphocytic lymphoma, marginal zone lymphoma, and follicular
      lymphoma. RISK STRATIFICATION: The mantle cell lymphoma international prognostic
      index (MIPI) is the prognostic model most often used and incorporates ECOG
      performance status, age, leukocyte count, and lactic dehydrogenase. A
      modification of the MIPI also adds the Ki-67 proliferative index if available.
      The median overall survival (OS) for the low-risk group was not reached (5-year
      OS of 60%). The median OS for the intermediate risk group was 51 and 29 months
      for the high-risk group. RISK-ADAPTED THERAPY: For selected indolent, low MIPI
      MCL patients, initial observation may be appropriate therapy. For younger
      patients with intermediate or high risk MIPI MCL, aggressive therapy with a
      cytarabine containing regimen +/- autologous stem cell transplantation should be
      considered. For older MCL patients with intermediate or high risk MIPI,
      combination chemotherapy with R-CHOP, R-Bendamustine, or a clinical trial should
      be considered. At the time of relapse, agents directed at activated pathways in
      MCL cells such as bortezomib (NFkB inhibitor), BTK inhibitors or CAL-101 (B-cell
      receptor inhibitors) or lenalidamide (antiangiogenesis) have clinical activity in
      MCL patients. Autologous or allogeneic stem cell transplantation can also be
      considered in young patients.

PMID- 22615103
TI  - Chronic myelomonocytic leukemia: 2012 update on diagnosis, risk stratification,
      and management.
AB  - DISEASE OVERVIEW: Chronic myelomonocytic leukemia (CMML) is a clonal
      hematopoietic stem cell disorder that is classified as a
      myelodysplastic/myeloproliferative neoplasm by the 2008 World Health Organization
      classification of hematopoietic tumors. It is characterized by absolute
      monocytosis (>1 * 10(9) L(-1) ) in the peripheral blood that persists for at
      least 3 months. Patients may present with symptoms related to cytopenias and/or
      an underlying hypercatabolic state with drenching night sweats, splenomegaly, and
      weight loss. DIAGNOSIS: The diagnosis of CMML rests on a combination of
      morphologic, histopathologic, and chromosomal abnormalities in the bone marrow,
      after careful exclusion of other conditions (both malignant and nonmalignant)
      that can cause monocytosis. Numerous molecular abnormalities have been recently
      recognized in patients with CMML-unfortunately, no single pathognomonic finding
      specific to CMML has been identified thus far. RISK STRATIFICATION: The
      International Prognostic Scoring System for myelodysplastic syndrome (MDS) cannot
      be used to risk stratify patients with CMML because this model excluded patients
      with a leukocyte count >12 * 10(9) L(-1) . Other risk stratification models such
      as the MD Anderson prognostic score and Dusseldorf score have been published. In
      the only model that took karyotype into account, bone marrow blasts >= 10%,
      leukocyte count >= 13 * 10(9) L(-1) , hemoglobin < 10 g/dL, platelet count < 100
      * 10(9) L(-1) , and presence of trisomy 8, abnormalities of chromosome 7, or
      complex karyotype were found to be independent predictors of adverse survival.
      RISK-ADAPTED THERAPY: The Food and Drug Administration has approved azacitidine
      and decitabine for the treatment of patients with CMML based on two pivotal
      trials in MDS. Novel classes of agents including immunomodulatory drugs,
      nucleoside analogs, and small-molecule tyrosine kinase inhibitors are being
      investigated in the treatment of CMML. With the advent of reduced intensity
      conditioning, an allogeneic stem cell transplant has also become a viable option
      for a subset of patients.

PMID- 22615104
TI  - E-cadherin upregulates expression of matrix macromolecules aggrecan and collagen
      II in the intervertebral disc cells through activation of the intracellular BMP
      Smad1/5 pathway.
AB  - E-cadherin is a transmembrane protein that mediates cell-cell adhesion and cell
      matrix interaction. Although the E-cadherin has been shown to mediate a broad
      ranging cellular signals and functions, its effects on matrix metabolism of
      intervertebral discs (IVDs) are unknown. In this study, we investigated the
      effects of E-cadherin on IVD matrix synthesis using pharmacological and molecular
      biology methods. We showed that high levels of the E-cadherin are expressed in
      rabbits IVD cells. Our study indicates that the ectopic expression of E-cadherin
      can stimulate matrix anabolism of the IVD cells, which was evidenced by increased
      expression of the matrix macromolecules aggrecan and collagen II. We found that E
      cadherin induces the expression of BMP-4 and BMP-7 genes and enhances Smad1/5
      phosphorylation. Blocking BMP activity uses noggin suppressed E-cadherin-mediated
      upregulation of aggrecan and collagen II. Moreover, inhibition of Smad1/5
      phosphorylation by dorsomorphin significantly repressed the E-cadherin induced
      expression of aggrecan and collagen II at the both mRNA and protein levels.
      Together this study demonstrates that the E-cadherin stimulates the synthesis of
      IVD matrix macromolecules aggrecan and collagen II through the induction of BMP
      genes and enhancement of the Smad1/5 phosphorylation. Thus E-cadherin may have
      value in the treatment of degenerated discs.

PMID- 22615106
TI  - Morphological characterization of the nymphs Rhipicephalus sanguineus ticks
      (Latreille, 1806) (Acari: Ixodidae). Description of the testes, integument,
      Malpighian tubules, and midgut on the detachment day.
AB  - This study presents the morpho-histological and histochemical characterization of
      the testes, integument, Malpighian tubules, and midgut of engorged Rhipicephalus
      sanguineus nymphs on the detachment day, showing the morphological and
      physiological characteristics to this phase in the life cycle of these
      individuals. The testis is constituted by germinative cells (only spermatogonia)
      with large, round-shaped and strongly stained nuclei which are organized into
      cysts by a thin layer of somatic cells. The integument consists of a cuticle
      subdivided into epicuticle (lipoprotein) and procuticle (glycoproteic), and a
      layer of epithelial cells which present glycolipoprotein elements. The procuticle
      presents two distinct regions: the exocuticle (next to the epicuticle) and the
      endocuticle (next to the epithelial layer). The Malpighian tubules present a
      simple epithelium with small flat and/or cubic cells, which form its wall and
      delimitates a lumen full of lipoprotein material. The midgut consists of an
      epithelial wall formed by two types of digestive cells, spent cells and empty
      digest cells, and by generative cells supported by a basal lamina and a thin
      layer of muscular tissue. This study described the main organs of engorged nymphs
      of R. sanguineus, to generate information that can help researchers to better
      understand the biology of these ectoparasites; which is fundamental for the
      development of compounds that are less aggressive to the environment. In
      addition, if the immature stages of the ticks are controlled, the number of adult
      ticks able to cause damages to the animals--and to the man as well--is also under
      control.

PMID- 22615107
TI  - Automated signal pattern evaluation of a bladder cancer specific multiprobe-fish
      assay applying a user-trainable workstation.
AB  - OBJECTIVE: Signal pattern enumeration of Urovysion Fluorescence in Situ
      Hybridization test is tedious and requires great experience. Our aim was to
      eliminate human interaction by automating the process, using an adoptable,
      automated image acquisition, and analysis system. METHODS: For extensive
      analytical analysis control, cell populations were used, while preliminary
      clinical study was performed on 21 patients with clinical suspicion for bladder
      cancer. All investigations were carried out using an automated user-trainable
      workstation (Metafer4-Metacyte). RESULTS: The system identified nuclei with a
      specificity and sensitivity of 92.7 and 96.6%, respectively, while signal
      detection accuracy was 81.1% on average. Both analytical and diagnostic accuracy
      of automated analysis was comparable to manual approach (94.8 and 71% vs. 97.9
      and 76%, respectively), but classification accuracy increased with degree of
      polysomy, thus diagnostic sensitivity in low grade, low stage cases was poor.
      CONCLUSION: It is possible to automate signal enumeration of Urovysion using a
      user-trainable system, and achieve efficiency comparable to manual analysis.
      Previously introduced automated immunophenotypic targeting should further
      increase diagnostic sensitivity, while resulting in a comprehensively automated
      method. However, the problem of reduced detection accuracy in cases featured with
      low polysomy is likely to remain a great challenge of automated signal
      enumeration.

PMID- 22615105
TI  - In situ crosslinkable heparin-containing poly(ethylene glycol) hydrogels for
      sustained anticoagulant release.
AB  - Low-molecular weight heparin (LMWH) is widely used in anticoagulation therapies
      and for the prevention of thrombosis. LMWH is administered by subcutaneous
      injection usually once or twice per day. This frequent and invasive delivery
      modality leads to compliance issues for individuals on prolonged therapeutic
      courses, particularly pediatric patients. Here, we report a long-term delivery
      method for LMWH via subcutaneous injection of long-lasting hydrogels. LMWH is
      modified with reactive maleimide groups so that it can be crosslinked into
      continuous networks with four-arm thiolated poly(ethylene glycol) (PEG-SH).
      Maleimide-modified LMWH (Mal-LMWH) retains bioactivity as indicated by prolonged
      coagulation time. Hydrogels comprising PEG-SH and Mal-LMWH degrade via
      hydrolysis, releasing bioactive LMWH by first-order kinetics with little initial
      burst release. Separately dissolved Mal-LMWH and PEG-SH solutions were co
      injected subcutaneously in New Zealand White rabbits. The injected solutions
      successfully formed hydrogels in situ and released LMWH as measured via
      chromogenic assays on plasma samples, with accumulation of LMWH occurring at day
      2 and rising to near-therapeutic dose equivalency by day 5. These results
      demonstrate the feasibility of using LMWH-containing, crosslinked hydrogels for
      sustained and controlled release of anticoagulants.

PMID- 22615108
TI  - Results of community deliberation about social impacts of ecological restoration:
      comparing public input of self-selected versus actively engaged community
      members.
AB  - Participatory processes for obtaining residents' input about community impacts of
      proposed environmental management actions have long raised concerns about who
      participates in public involvement efforts and whose interests they represent.
      This study explored methods of broad-based involvement and the role of
      deliberation in social impact assessment. Interactive community forums were
      conducted in 27 communities to solicit public input on proposed alternatives for
      recovering wild salmon in the Pacific Northwest US. Individuals identified by
      fellow residents as most active and involved in community affairs ("AE
      residents") were invited to participate in deliberations about likely social
      impacts of proposed engineering and ecological actions such as dam removal.
      Judgments of these AE participants about community impacts were compared with the
      judgments of residents motivated to attend a forum out of personal interest, who
      were designated as self-selected ("SS") participants. While the magnitude of
      impacts rated by SS participants across all communities differed significantly
      from AE participants' ratings, in-depth analysis of results from two community
      case studies found that both AE and SS participants identified a large and
      diverse set of unique impacts, as well as many of the same kinds of impacts.
      Thus, inclusion of both kinds of residents resulted in a greater range of impacts
      for consideration in the environmental impact study. The case study results also
      found that the extent to which similar kinds of impacts are specified by AE and
      SS group members can differ by type of community. Study results caution against
      simplistic conclusions drawn from this approach to community-wide public
      participation. Nonetheless, the results affirm that deliberative methods for
      community-based impact assessment involving both AE and SS residents can provide
      a more complete picture of perceived impacts of proposed restoration activities.

PMID- 22615110
TI  - Arteriosclerosis: inevitable or self-inflicted?

PMID- 22615109
TI  - Hypertension induces brain beta-amyloid accumulation, cognitive impairment, and
      memory deterioration through activation of receptor for advanced glycation end
      products in brain vasculature.
AB  - Although epidemiological data associate hypertension with a strong predisposition
      to develop Alzheimer disease, no mechanistic explanation exists so far. We
      developed a model of hypertension, obtained by transverse aortic constriction,
      leading to alterations typical of Alzheimer disease, such as amyloid plaques,
      neuroinflammation, blood-brain barrier dysfunction, and cognitive impairment,
      shown here for the first time. The aim of this work was to investigate the
      mechanisms involved in Alzheimer disease of hypertensive mice. We focused on
      receptor for advanced glycation end products (RAGE) that critically regulates
      Abeta transport at the blood-brain barrier and could be influenced by vascular
      factors. The hypertensive challenge had an early and sustained effect on RAGE
      upregulation in brain vessels of the cortex and hippocampus. Interestingly, RAGE
      inhibition protected from hypertension-induced Alzheimer pathology, as showed by
      rescue from cognitive impairment and parenchymal Abeta deposition. The increased
      RAGE expression in transverse aortic coarctation mice was induced by increased
      circulating advanced glycation end products and sustained by their later
      deposition in brain vessels. Interestingly, a daily treatment with an advanced
      glycation end product inhibitor or antioxidant prevented the development of
      Alzheimer traits. So far, Alzheimer pathology in experimental animal models has
      been recognized using only transgenic mice overexpressing amyloid precursor. This
      is the first study demonstrating that a chronic vascular insult can activate
      brain vascular RAGE, favoring parenchymal Abeta deposition and the onset of
      cognitive deterioration. Overall we demonstrate that RAGE activation in brain
      vessels is a crucial pathogenetic event in hypertension-induced Alzheimer
      disease, suggesting that inhibiting this target can limit the onset of vascular
      related Alzheimer disease.

PMID- 22615111
TI  - Endothelial nitric oxide synthase deficiency reduces uterine blood flow, spiral
      artery elongation, and placental oxygenation in pregnant mice.
AB  - Preeclampsia is associated with impaired uteroplacental adaptations during
      pregnancy and abnormalities in the endothelial NO synthase (eNOS)-NO pathway, but
      whether eNOS deficiency plays a causal role is unknown. Thus, the objective of
      the current study was to determine the role of eNOS in the mother and/or
      conceptus in uteroplacental changes during pregnancy using eNOS knockout mice. We
      quantified uterine artery blood flow using microultrasound, visualized the
      uteroplacental vasculature using vascular corrosion casts, and used pimonidazole
      and hypoxia-inducible factor 1alpha immunohistochemistry as markers of hypoxia in
      the placentas of eNOS knockout mice versus the background strain, C57Bl/6J (wild
      type). We found that increases in uteroplacental blood flow, uterine artery
      diameter, and spiral artery length were reduced, and markers of placental hypoxia
      in the junctional zone were elevated in late gestation in eNOS knockout mice.
      Both maternal and conceptus genotypes contributed to changes in uterine artery
      diameter and flow. Despite placental hypoxia, placental soluble fms-like tyrosine
      kinase 1 and tumor necrosis factor-alpha mRNA, and in maternal plasma, soluble
      fms-like tyrosine kinase 1 were not elevated in eNOS knockout mice. Thus, our
      results show that both eNOS in the mother and the conceptus contribute to
      uteroplacental vascular changes and increased uterine arterial blood flow in
      normal pregnancy.

PMID- 22615112
TI  - Ethnic differences in blood pressure and hypertensive complications during
      pregnancy: the Generation R study.
AB  - The aim was to investigate ethnic differences in blood pressure levels in each
      trimester of pregnancy and the risk of gestational hypertensive disorders and the
      degree to which such differences can be explained by education and lifestyle
      related factors. The study included 6215 women participating in a population
      based prospective cohort study from early pregnancy onward in Rotterdam.
      Ethnicity was assessed at enrollment. Blood pressure was measured in each
      trimester. Information about gestational hypertensive disorders was available
      from medical charts. Lifestyle factors included smoking, alcohol, caffeine
      intake, folic acid supplementation, sodium and energy intake, body mass index,
      and maternal stress. Associations and explanatory pathways were investigated
      using linear and logistic regression analysis. Dutch pregnant women had higher
      systolic blood pressure levels as compared with women in other ethnic groups in
      each trimester of pregnancy. Compared with Dutch women, Turkish and Moroccan
      women had lower diastolic blood pressure levels in each trimester. These
      differences remained after adjusting for education and lifestyle factors. Turkish
      and Moroccan women had a lower risk of gestational hypertension as compared with
      Dutch women (odds ratio, 0.32 [95% CI, 0.18-0.58] and odds ratio, 0.28 [95% CI,
      0.14-0.58]), and Cape Verdean women had an elevated risk of preeclampsia (odds
      ratio, 2.22 [95% CI, 1.22-4.07]). Differences could not be explained by education
      or lifestyle. Substantial ethnic differences were observed in blood pressure
      levels and risk of gestational hypertensive disorders in each trimester of
      pregnancy, and a wide range of variables could not explain these differences.

PMID- 22615113
TI  - Blood pressure and retinal microvascular characteristics during pregnancy:
      Growing Up in Singapore Towards Healthy Outcomes (GUSTO) Study.
AB  - Changes in maternal blood pressure during pregnancy are associated with poor
      maternal and neonatal outcomes. We investigated whether maternal blood pressure
      during midpregnancy has an impact on the retinal microcirculation among pregnant
      Asian women. A total of 665 pregnant women aged 18 to 46 years were recruited
      from the Growing Up in Singapore Towards Healthy Outcomes Study. Blood pressure
      and retinal vascular parameters were both measured at 26 weeks' gestation
      following a standardized protocol. Blood pressure was measured by a digital
      automatic blood pressure monitor (Omron HEM 705 LP). Quantitative retinal
      vascular parameters were assessed by a semiautomated computer-based program
      (Singapore I Vessel Assessment, version 3.0). In multiple linear regression
      models, every 10-mm Hg increase in mean arterial blood pressure was associated
      with a 1.9-MUm (P<0.001) reduction in retinal arteriolar caliber, a 0.9 degrees 
      (P=0.05) reduction in retinal arteriolar branching angle, and a 0.07 (P<0.01)
      reduction in retinal arteriolar fractal dimension, respectively. Patients
      classified into a high-risk group in developing preeclampsia (mean arterial blood
      pressure >= 90 mm Hg) were twice as likely (odds ratio 2.1 [95% CI, 1.0-4.4]) to
      have generalized retinal arteriolar narrowing compared with those classified into
      a low-risk group (mean arterial blood pressure <90 mm Hg). Retinal venular
      caliber and vascular tortuosity were not associated with blood pressure measures.
      Elevated blood pressure is associated with a range of retinal arteriolar changes
      in pregnant women, providing evidence for an impact of blood pressure on the
      microcirculation during pregnancy.

PMID- 22615114
TI  - Effects of hunter-gatherer subsistence mode on arterial distensibility in
      Cameroonian pygmies.
AB  - We aimed to assess whether arterial distensibility estimated by pulse wave
      velocity (PWV) and augmentation index (AI) differs between Cameroon traditional
      pygmies (TPs) on hunter-gather subsistence mode, contemporary pygmies who
      migrated to semiurban area, and the Bantou farmers (BFs) sharing the same
      environment. For that purpose, we recorded carotid-femoral PWV (ComplioR) in age
      and sex carefully matched 20 TPs, 20 contemporary pygmies, and 22 BFs. Aortic AI
      corrected for heart rate and blood pressures were generated from pressure wave
      analysis (SphygmoCor). Lipid profile was determined in TP and BF participants.
      TPs were shorter (P=0.02) with lower body weight (P<0.01) in comparison with
      contemporary pygmies and BFs. TPs had lower low-density lipoprotein cholesterol
      but higher high-density lipoprotein cholesterol than BFs (P<0.01). Their PWV
      (5.81+/-0.21 m/s) was slower (P=0.006) than that of contemporary pygmies (6.82+/
      0.36 m/s) or BFs (6.93+/-0.29 m/s); however, after its adjustment for age, mean
      arterial pressure, and heart rate, the difference was slightly attenuated
      (P=0.051). PWV adjusted for weight did not differ between groups (P=0.10). In the
      whole study population but not in TPs taken separately, multivariate regression
      analysis revealed that PWV was independently associated with mean arterial
      pressure, age, and TP status (P<0.001), whereas age, mean arterial pressure, and
      height emerged as independent determinants of aortic AI corrected for heart rate
      (P<0.001). Aortic AI corrected for heart rate did not differ in the 3 groups. In
      conclusion, hunter-gather lifestyle is associated with low atherosclerosis risk
      translated by lower aortic stiffness attributed at least partly to low weight and
      blunted effects of aging and blood pressures on TP arterial structure and
      function.

PMID- 22615115
TI  - Atorvastatin inhibits myocardin expression in vascular smooth muscle cells.
AB  - Atorvastatin (ATV), an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A
      reductase, is widely prescribed as a lipid-lowering drug. It also inhibits the
      RhoA-Rho-associated kinase pathway in vascular smooth muscle (SM) cells and
      critically inhibits SM function. Myocardin is a coactivator of serum response
      factor, which upregulates SM contractile proteins. The RhoA-Rho-associated kinase
      pathway, which directly triggers SM contraction, also increases myocardin gene
      expression. Therefore, we investigated whether ATV inhibits myocardin gene
      expression in SM cells. In mice injected with ATV (IP 20 MUg/g per day) for 5
      days, myocardin gene expression was significantly downregulated in aortic and
      carotid arterial tissues with decreased expression of myocardin target genes SM
      alpha-actin and SM22. Correspondingly, the contractility of aortic rings in mice
      treated with ATV or the Rho-associated kinase inhibitor Y-27632 was reduced in
      response to treatment with either KCl or phenylephrine. In cultured mouse and
      human aortic SM cells, KCl treatment stimulated the expression of myocardin, SM
      alpha-actin, and SM22. These stimulatory effects were prevented by ATV treatment.
      ATV-induced inhibition of myocardin expression was prevented by pretreatment with
      either mevalonate or geranylgeranylpyrophosphate but not farnesylpyrophosphate.
      Treatment with Y-27632 mimicked ATV effects on the gene expression of myocardin,
      SM alpha-actin, and SM22, further suggesting a role for the RhoA-Rho-associated
      kinase pathway in ATV effects. Furthermore, ATV treatment inhibited RhoA membrane
      translocation and activation; these effects were prevented by pretreatment with
      mevalonate. We conclude that ATV inhibits myocardin gene expression in vivo and
      in vitro, suggesting a novel mechanism for ATV inhibition of vascular
      contraction.

PMID- 22615116
TI  - Effect of home blood pressure telemonitoring with self-care support on
      uncontrolled systolic hypertension in diabetics.
AB  - Lowering blood pressure reduces cardiovascular risk, yet hypertension is poorly
      controlled in diabetic patients. In a pilot study we demonstrated that a home
      blood pressure telemonitoring system, which provided self-care messages on the
      smartphone of hypertensive diabetic patients immediately after each reading,
      improved blood pressure control. Messages were based on care paths defined by
      running averages of transmitted readings. The present study tests the system's
      effectiveness in a randomized, controlled trial in diabetic patients with
      uncontrolled systolic hypertension. Of 244 subjects screened for eligibility, 110
      (45%) were randomly allocated to the intervention (n = 55) or control (n = 55)
      group, and 105 (95.5%) completed the 1-year outcome visit. In the intention-to
      treat analysis, mean daytime ambulatory systolic blood pressure, the primary end
      point, decreased significantly only in the intervention group by 9.1 +/- 15.6
      mmHg (SD; P < 0.0001), and the mean between-group difference was 7.1 +/- 2.3 mmHg
      (SE; P < 0.005). Furthermore, 51% of intervention subjects achieved the guideline
      recommended target of <130/80 mmHg compared with 31% of control subjects (P <
      0.05). These improvements were obtained without the use of more or different
      antihypertensive medications or additional clinic visits to physicians. Providing
      self-care support did not affect anxiety but worsened depression on the Hospital
      Anxiety and Depression Scale (baseline, 4.1 +/- 3.76; exit, 5.2 +/- 4.30; P =
      0.014). This study demonstrated that home blood pressure telemonitoring combined
      with automated self-care support reduced the blood pressure of diabetic patients
      with uncontrolled systolic hypertension and improved hypertension control. Home
      blood pressure monitoring alone had no effect on blood pressure. Promoting
      patient self-care may have negative psychological effects.

PMID- 22615117
TI  - "From apennines to andes:" does body mass index affect the relationship between
      age and blood pressure?

PMID- 22615118
TI  - The effects of male attractiveness and sexual attitudes on women's risk
      perception.
AB  - This study examined the effects of male attractiveness, sexual attitudes, and
      victimization history on women's ratings of sexual risk. Women with more liberal
      sexual attitudes rated vignettes as less sexually risky than women with more
      conservative sexual attitudes. There was an interaction between situational risk
      and attractiveness, suggesting the relationship between attractiveness and sexual
      risk ratings varies across high and low situational risk. Findings emphasize the
      importance of using high and low risk situations to evaluate sexual risk
      perception and of investigating variables that may moderate women's risk
      perception.

PMID- 22615119
TI  - Does alcohol consumption exacerbate the mental health consequences of
      interpersonal violence?
AB  - Although studies show that interpersonal violence is associated with poorer
      mental health, few studies specify the conditions under which victimization can
      be more or less detrimental to psychological well-being. Building on previous
      research, the authors test whether the association between interpersonal violence
      and psychological distress is moderated by alcohol consumption. Our analysis of
      longitudinal data from the Welfare, Children, and Families project suggests that
      interpersonal violence is more strongly associated with psychological distress in
      the context of more frequent intoxication. Programs designed to treat the
      combination of victimization and heavy alcohol consumption may make unique
      contributions to the well-being of women.

PMID- 22615120
TI  - School-based sexual violence among female learners with mild intellectual
      disability in South Africa.
AB  - Following qualitative research methodology, this article presents school-based
      sexual violence experiences of female learners with mild intellectual disability.
      A total of 16 learners aged 16 to 24 years participated in the study. The
      findings revealed that learners with intellectual disability are not immune to
      school-based sexual violence. Modes of behavior that occurred frequently included
      touching, threats, and intimidation. School practices that reinforced school
      based sexual violence are identified. The findings contradict common
      misconceptions that people with intellectual disability do not understand what is
      happening to them. The study recommends that school policies for sexual violence
      be intensified and learners receive developmentally appropriate sex education.

PMID- 22615121
TI  - Violence against women in the militarized Indian frontier: beyond "Indian
      culture" in the experiences of ethnic minority women.
AB  - Violence against women (VAW) in India is commonly attributed to an overarching
      metacultural patriarchal framework. Focusing on this national culture of violence
      obscures the experiences of VAW among ethnic minority women. This article focuses
      on VAW in Northeast India, a region populated by large numbers of Scheduled
      Tribes with different cultural norms, and where society has become militarized by
      ongoing insurgency and counterinsurgency. Though tempting, militarization alone
      is not a sufficient explanation for VAW; instead, this article focuses on the
      interplay between nonfamilial and familial contexts in creating a "frontier
      culture of violence" in which VAW is experienced and contested.

PMID- 22615122
TI  - Letter to the Editor regarding "Exiting prostitution: an integrated model," by L.
      M. Baker, R. L. Dalla, & C. Williamson, Violence Against Women, 16, 579-600.

PMID- 22615123
TI  - Microbial catalysis of the oxygen reduction reaction for microbial fuel cells: a
      review.
AB  - The slow kinetics of the electrochemical oxygen reduction reaction (ORR) is a
      crucial bottleneck in the development of microbial fuel cells (MFCs). This
      article firstly gives an overview of the particular constraints imposed on ORR by
      MFC operating conditions: neutral pH, slow oxygen mass transfer, sensitivity to
      reactive oxygen species, fouling and biofouling. A review of the literature is
      then proposed to assess how microbial catalysis could afford suitable solutions.
      Actually, microbial catalysis of ORR occurs spontaneously on the surface of
      metallic materials and is an effective motor of microbial corrosion. In this
      framework, several mechanisms have been proposed, which are reviewed in the
      second part of the article. The last part describes the efforts made in the
      domain of MFCs to determine the microbial ecology of electroactive biofilms and
      define efficient protocols for the formation of microbial oxygen-reducing
      cathodes. Although no clear mechanism has been established yet, several promising
      solutions have been recently proposed.

PMID- 22615124
TI  - The catalytic redox activity of prion protein-Cu(II) is controlled by metal
      exchange with the Zn(II) -thiolate clusters of Zn(7) metallothionein-3.
AB  - Silencing prion: Copper-catalyzed transformations of prion protein (PrP) lead to
      the production of reactive oxygen species (ROS), PrP oxidation, and cleavage and
      aggregation in transmissible spongiphorm encephalopathies. Zn(7) MT-3 efficiently
      targets Cu(II)  bound in different coordination modes to PrP-Cu(II) . By an
      unusual redox-dependent metal-swap reaction, MT-3 modulates the catalytic redox
      properties of PrP-Cu(II) .

PMID- 22615125
TI  - Piezochromism in nickel salicylaldoximato complexes: tuning crystal-field
      splitting with high pressure.
AB  - The crystal structures of bis(3-fluoro-salicylaldoximato)nickel(II) and bis(3
      methoxy-salicylaldoximato)nickel(II) have been determined at room temperature
      between ambient pressure and approximately 6 GPa. The principal effect of
      pressure is to reduce intermolecular contact distances. In the fluoro system
      molecules are stacked, and the Ni???Ni distance decreases from 3.19 A at ambient
      pressure to 2.82 A at 5.4 GPa. These data are similar to those observed in
      bis(dimethylglyoximato)nickel(II) over a similar pressure range, though contrary
      to that system, and in spite of their structural similarity, the salicyloximato
      does not become conducting at high pressure. Ni-ligand distances also shorten, on
      average by 0.017 and 0.011 A for the fluoro and methoxy complexes, respectively.
      Bond compression is small if the bond in question is directed towards an
      interstitial void. A band at 620 nm, which occurs in the visible spectrum of each
      derivative, can be assigned to a transition to an antibonding molecular orbital
      based on the metal 3d(x(2)-y(2)) orbital. Time-dependent density functional
      theory calculations show that the energy of this orbital is sensitive to
      pressure, increasing in energy as the Ni-ligand distances are compressed, and
      consequently increasing the energy of the transition. The resulting blueshift of
      the UV-visible band leads to piezochromism, and crystals of both complexes, which
      are green at ambient pressure, become red at 5 GPa.

PMID- 22615126
TI  - Uniaxial mechanical tension promoted osteogenic differentiation of rat tendon
      derived stem cells (rTDSCs) via the Wnt5a-RhoA pathway.
AB  - Chronic tendinopathy is a tendon disorder that is common in athletes and
      individuals whose tendons are subjected to repetitive strain injuries. The
      presence of ossification worsened the clinical manifestation of the disorder. The
      change of tendon loading due to mechanical overload, compression, or disuse have
      been implicated as the possible etiologies, but the pathological mechanisms of
      tendinopathy remain unclear. In this study, we demonstrated that ossification in
      tendon tissue might be due to the osteogenesis of tendon-derived stem cells
      (TDSCs) induced by uniaxial mechanical tension (UMT) which mimics the mechanical
      loading in tendon. Rat TDSCs (rTDSCs) could be induced to differentiate into
      osteogenic lineage after treatment with 2% elongation UMT for 3 days as shown by
      the increased expression Runx2 mRNA and protein, Alpl mRNA, collagen type 1 alpha
      1 (Col1a1) mRNA, ALP activity, and ALP cytochemical staining. RhoA, an
      osteogenesis regulator, was activated in rTDSCs upon UMT stimulation. Blockage of
      RhoA activity in rTDSCs by C3 toxin or ROCK activity, a downstream target of
      RhoA, by Y-27632 inhibited UMT-induced osteogenesis in rTDSCs. UMT up-regulated
      the mRNA expression of Wnt5a but not the other non-canonical Wnts. The inhibition
      of Wnt5a expression by siRNA abolished UMT-induced Runx2 mRNA expression and RhoA
      activation in rTDSCs and the inhibition of Runx2 expression could be rescued by
      addition of LPA, a RhoA activator. In conclusion, our results showed that UMT
      induced osteogenic differentiation of rTDSCs via the Wnt5a-RhoA pathway, which
      might contribute to ectopic ossification in tendon tissue due to mechanical
      loading.

PMID- 22615128
TI  - DNA polymerase zeta generates tandem mutations in immunoglobulin variable
      regions.
AB  - Low-fidelity DNA polymerases introduce nucleotide substitutions in immunoglobulin
      variable regions during somatic hypermutation. Although DNA polymerase (pol) eta
      is the major low-fidelity polymerase, other DNA polymerases may also contribute.
      Existing data are contradictory as to whether pol zeta is involved. We reasoned
      that the presence of pol eta may mask the contribution of pol zeta, and therefore
      we generated mice deficient for pol eta and heterozygous for pol zeta. The
      frequency and spectra of hypermutation was unaltered between Polzeta(+/-) Poleta(
      /-) and Polzeta(+/+) Poleta(-/-) clones. However, there was a decrease in tandem
      double-base substitutions in Polzeta(+/-) Poleta(-/-) cells compared with
      Polzeta(+/+) Poleta(-/-) cells, suggesting that pol zeta generates tandem
      mutations. Contiguous mutations are consistent with the biochemical property of
      pol zeta to extend a mismatch with a second mutation. The presence of this unique
      signature implies that pol zeta contributes to mutational synthesis in vivo.
      Additionally, data on tandem mutations from wild type, Polzeta(+/-), Polzeta(-/
      ), Ung(-/-), Msh2(-/-), Msh6(-/-), and Ung(-/-) Msh2(-/-) clones suggest that pol
      zeta may function in the MSH2-MSH6 pathway.

PMID- 22615127
TI  - Zbtb46 expression distinguishes classical dendritic cells and their committed
      progenitors from other immune lineages.
AB  - Distinguishing dendritic cells (DCs) from other cells of the mononuclear
      phagocyte system is complicated by the shared expression of cell surface markers
      such as CD11c. In this study, we identified Zbtb46 (BTBD4) as a transcription
      factor selectively expressed by classical DCs (cDCs) and their committed
      progenitors but not by plasmacytoid DCs (pDCs), monocytes, macrophages, or other
      lymphoid or myeloid lineages. Using homologous recombination, we replaced the
      first coding exon of Zbtb46 with GFP to inactivate the locus while allowing
      detection of Zbtb46 expression. GFP expression in Zbtb46(gfp/+) mice
      recapitulated the cDC-specific expression of the native locus, being restricted
      to cDC precursors (pre-cDCs) and lymphoid organ- and tissue-resident cDCs. GFP(+)
      pre-cDCs had restricted developmental potential, generating cDCs but not pDCs,
      monocytes, or macrophages. Outside the immune system, Zbtb46 was expressed in
      committed erythroid progenitors and endothelial cell populations. Zbtb46
      overexpression in bone marrow progenitor cells inhibited granulocyte potential
      and promoted cDC development, and although cDCs developed in Zbtb46(gfp/gfp)
      (Zbtb46 deficient) mice, they maintained expression of granulocyte colony
      stimulating factor and leukemia inhibitory factor receptors, which are normally
      down-regulated in cDCs. Thus, Zbtb46 may help enforce cDC identity by restricting
      responsiveness to non-DC growth factors and may serve as a useful marker to
      identify rare cDC progenitors and distinguish between cDCs and other mononuclear
      phagocyte lineages.

PMID- 22615129
TI  - Pericytes support neutrophil subendothelial cell crawling and breaching of
      venular walls in vivo.
AB  - Neutrophil transmigration through venular walls that are composed of endothelial
      cells (ECs), pericytes, and the venular basement membrane is a key component of
      innate immunity. Through direct analysis of leukocyte-pericyte interactions in
      inflamed tissues using confocal intravital microscopy, we show how pericytes
      facilitate transmigration in vivo. After EC migration, neutrophils crawl along
      pericyte processes to gaps between adjacent pericytes in an ICAM-1-, Mac-1-, and
      LFA-1-dependent manner. These gaps were enlarged in inflamed tissues through
      pericyte shape change and were used as exit points by neutrophils in breaching
      the venular wall. The findings identify previously unknown roles for pericytes in
      neutrophil transmigration in vivo and add additional steps to the leukocyte
      adhesion cascade that supports leukocyte trafficking into sites of inflammation.

PMID- 22615131
TI  - Application of HSQC in the delineation of NMR signals of E and Z isomers of
      octadecyl p-coumarates.
AB  - Octadecyl p-coumarates undergo E-Z isomerization in daylight. Although (1) H NMR,
      (13) C NMR and (1) H-(1) H COSY gave indications about this isomerization, the
      overlapping of some signals in the (1) H NMR of aromatic region prevented the
      delineation of signals of the individual isomers. However, heteronuclear spin
      quantum coupling correlation (HSQC) with the unique feature of two sets of nearby
      delta(C) -delta(H) correlations gave conclusive evidence for this isomerization
      and helped in the delineation of (1) H NMR and (13) C NMR signals of E-octadecyl
      p-coumarate and Z-octadecyl p-coumarate.

PMID- 22615130
TI  - Expression of the zinc finger transcription factor zDC (Zbtb46, Btbd4) defines
      the classical dendritic cell lineage.
AB  - Classical dendritic cells (cDCs), monocytes, and plasmacytoid DCs (pDCs) arise
      from a common bone marrow precursor (macrophage and DC progenitors [MDPs]) and
      express many of the same surface markers, including CD11c. We describe a
      previously uncharacterized zinc finger transcription factor, zDC (Zbtb46, Btbd4),
      which is specifically expressed by cDCs and committed cDC precursors but not by
      monocytes, pDCs, or other immune cell populations. We inserted diphtheria toxin
      (DT) receptor (DTR) cDNA into the 3' UTR of the zDC locus to serve as an
      indicator of zDC expression and as a means to specifically deplete cDCs. Mice
      bearing this knockin express DTR in cDCs but not other immune cell populations,
      and DT injection into zDC-DTR bone marrow chimeras results in cDC depletion. In
      contrast to previously characterized CD11c-DTR mice, non-cDCs, including pDCs,
      monocytes, macrophages, and NK cells, were spared after DT injection in zDC-DTR
      mice. We compared immune responses to Toxoplasma gondii and MO4 melanoma in DT
      treated zDC- and CD11c-DTR mice and found that immunity was only partially
      impaired in zDC-DTR mice. Our results indicate that CD11c-expressing non-cDCs
      make significant contributions to initiating immunity to parasites and tumors.

PMID- 22615133
TI  - Directing epithelial to mesenchymal transition through engineered
      microenvironments displaying orthogonal adhesive and mechanical cues.
AB  - Cell interactions with their extracellular matrix (ECM) microenvironments play a
      major role in directing cellular processes that can drive wound healing and
      tissue regeneration but, if uncontrolled, lead to pathological progression. One
      such process, epithelial to mesenchymal transition (EMT), if finely controlled
      could have significant potential in regenerative medicine approaches. Despite
      recent findings that highlight the influence of biochemical and mechanical
      properties of the ECM on EMT, it is still unclear how these two orthogonal cues
      act synergistically to control epithelial cell phenotype. Here, we cultured lung
      epithelial cells on combinations of different mutants of fibronectin's cell
      binding domain that preferentially engage specific integrins and substrates of
      varying stiffness. Our results suggest that while stiff substrates induce
      spontaneous EMT, this response can be overcome by with fragments of fibronectin
      that support alpha3 and alpha5 integrin engagement. Furthermore, we found that
      substrate-induced EMT correlates with transforming growth factor beta activation
      by resident epithelial cells and is dependent on Rho/ROCK signaling. Suppressing
      cell-contractility was sufficient to maintain an epithelial phenotype. Our
      results suggest that integrin-specific engagement of fibronectin adhesive domains
      and the mechanics of the ECM act synergistically to direct EMT.

PMID- 22615134
TI  - Long-lived room-temperature deep-red-emissive intraligand triplet excited state
      of naphthalimide in cyclometalated Ir(III) complexes and its application in
      triplet-triplet annihilation-based upconversion.
AB  - Cyclometalated Ir(III) complexes with acetylide ppy and bpy ligands were prepared
      (ppy = 2-phenylpyridine, bpy = 2,2'-bipyridine) in which naphthal (Ir-2) and
      naphthalimide (NI) were attached onto the ppy (Ir-3) and bpy ligands (Ir-4)
      through acetylide bonds. [Ir(ppy)(3)] (Ir-1) was also prepared as a model
      complex. Room-temperature phosphorescence was observed for the complexes; both
      neutral and cationic complexes Ir-3 and Ir-4 showed strong absorption in the
      visible range (epsilon=39,600  M(-1)  cm(-1) at 402 nm and epsilon=25,100  M(-1) 
      cm(-1) at 404 nm, respectively), long-lived triplet excited states (tau(T)=9.30
      MUs and 16.45 MUs) and room-temperature red emission (lambda(em)=640 nm,
      Phi(p)=1.4 % and lambda(em)=627 nm, Phi(p)=0.3 %; cf. Ir-1: epsilon=16,600  M(-1)
      cm(-1) at 382 nm, tau(em)=1.16 MUs, Phi(p)=72.6 %). Ir-3 was strongly
      phosphorescent in non-polar solvent (i.e., toluene), but the emission was
      completely quenched in polar solvents (MeCN). Ir-4 gave an opposite response to
      the solvent polarity, that is, stronger phosphorescence in polar solvents than in
      non-polar solvents. Emission of Ir-1 and Ir-2 was not solvent-polarity-dependent.
      The T(1) excited states of Ir-2, Ir-3, and Ir-4 were identified as mainly
      intraligand triplet excited states ((3)IL) by their small thermally induced
      Stokes shifts (DeltaE(s)), nanosecond time-resolved transient difference
      absorption spectroscopy, and spin-density analysis. The complexes were used as
      triplet photosensitizers for triplet-triplet annihilation (TTA) upconversion and
      quantum yields of 7.1 % and 14.4 % were observed for Ir-2 and Ir-3, respectively,
      whereas the upconversion was negligible for Ir-1 and Ir-4. These results will be
      useful for designing visible-light-harvesting transition-metal complexes and for
      their applications as triplet photosensitizers for photocatalysis, photovoltaics,
      TTA upconversion, etc.

PMID- 22615132
TI  - Differences in early maladaptive schemas between a sample of young adult female
      substance abusers and a non-clinical comparison group.
AB  - Early maladaptive schemas, defined as cognitive and behavioural patterns of
      viewing oneself and the world that cause considerable distress, are increasingly
      being recognized as an important underlying correlate of mental health problems.
      Recent research has begun to examine early maladaptive schemas among individuals
      seeking treatment for substance abuse. Unfortunately, there is limited research
      on whether substance abusers score higher on early maladaptive schemas than non
      clinical controls. Thus, the current study examined whether a sample of young
      adult female substance abuse treatment seekers (n = 180) scored higher than a non
      clinical group of female college students (n = 284) on early maladaptive schemas.
      Results demonstrated that the substance abuse group scored higher than the non
      clinical group on 16 of the 18 early maladaptive schemas. In addition, a number
      of differences in early maladaptive schemas were large in effect size.
      Implications of these findings for future research and substance abuse treatment
      programmes are discussed. KEY PRACTITIONER MESSAGE: Young adult female substance
      users have a number of early maladaptive schemas that may be contributing to the
      onset and maintenance of substance use. Findings from the current study suggest
      that early maladaptive schemas are more prevalent among young adult female
      substance abusers than a non-clinical control group, even after controlling for
      demographic differences between groups. The treatment of substance abuse among
      young adults should consider targeting early maladaptive schemas.

PMID- 22615135
TI  - Enhancement of the promiscuous aldolase and dehydration activities of 4
      oxalocrotonate tautomerase by protein engineering.
AB  - Double play: The enzyme 4-oxalocrotonate tautomerase (4-OT) catalyzes not only
      the initial cross-coupling of acetaldehyde and benzaldehyde to yield 3-hydroxy-3
      phenylpropanal, but also the subsequent dehydration of this aldol compound to
      yield cinnamaldehyde as the final product. Mechanism-inspired engineering
      provided an active site mutant (F50A) with strongly enhanced aldol condensation
      activity.

PMID- 22615136
TI  - Progesterone and calcitriol attenuate inflammatory cytokines CXCL1 and CXCL2 in
      ovarian and endometrial cancer cells.
AB  - Cytokines/chemokines are key players in cancer-related inflammation. Increasing
      evidence suggests that chemokines produced by tumor cells are the mediators of
      metastasis. Thus, agents that can downregulate chemokines expression have
      potential against cancer metastasis. We have previously shown inhibition of
      ovarian and endometrial cancer cell growth with progesterone and calcitriol. In
      the present study, we evaluated the effect of these two agents on the expression
      of inflammatory genes. Using a RT-PCR array of inflammatory cytokines/chemokines
      and their receptors, we found a marked attenuation of CXCL1 and CXCL2 (GRO-alpha
      and -beta) in cancer cells by both treatments. Knockdown of NFkappaB resulted in
      a reduced expression of CXCL1 and CXCL2 and the inhibitory effect of progesterone
      and calcitriol on the expression of chemokines was abrogated in NFkappaB-silenced
      cancer cells. Silencing of IkappaBalpha increased the expression of CXCL1 and
      CXCL2 in cancer cells, which can be attributed to the increased activation of
      NFkappaB-p65, caused by the lack of its inhibitor. Progesterone and calcitriol
      induced inhibition was abolished in IkappaBalpha-knockdown cells. Our results
      demonstrate that suppression of IkappaBalpha phosphorylation by progesterone and
      calcitriol contributes to the reduced expression of CXCL1 and CXCL2.
      Downregulation of CXCL1 and CXCL2 was associated with a marked inhibition of
      metastasis-promoting genes. Overall, our results indicate that progesterone and
      calcitriol inhibit IkappaBalpha phosphorylation, NFkappaB activation, and the
      expression of NFkappaB regulated metastasis promoting genes. These results
      provide attractive data for the possible use of progesterone and calcitriol in
      the management of endometrial and ovarian tumors.

PMID- 22615137
TI  - Structural insights into the transmembrane domains of human copper transporter 1.
AB  - The human copper transporter 1 (hCtr1) mediates cellular uptake of copper and Pt
      based chemotherapeutic anticancer drugs. In this paper, we determined the three
      dimensional structure and oligomerization of the transmembrane domains (TMDs) of
      hCtr1 in 40% HFIP aqueous solution by using solution-state NMR spectroscopy. We
      firstly revealed that TMD1 forms an alpha-helical structure from Gly67 to Glu84
      and is dimerized by close packing of its C-terminal helix; TMD2 forms an alpha
      helical structure from Leu134 to Thr155 and is self-associated as a trimer by the
      hydrophobic contact of TMD2 monomers; TMD3 adopts a discontinuous helix
      structure, known as 'alpha-helix-coiled segment-alpha-helix', and is dimerized by
      the interaction between the N-terminal helices. The motif GxxxG in TMD3 is not
      fully involved in the helix, but partially unstructured as a linker between
      helices. The flexible linker of TMD3 may serve as a gating adapter to mediate
      pore on and off switch. The differences in the structure and aggregation of the
      TMD peptides may be related to their different roles in the channel formation and
      transport function.

PMID- 22615138
TI  - Real-time mechanistic monitoring of an acetal hydrolysis using ultrafast 2D NMR.
AB  - Ultrafast (UF) 2D NMR makes it possible to obtain a 2D NMR spectrum in less than
      a second. Here, UF-HSQC experiments are used for the real-time mechanistic study
      of an acetal hydrolysis at 13C natural abundance, and it is possible to
      characterize the presence of the hemiacetal, an intermediate with a well-known
      short lifetime. The assignments are confirmed and rationalized by quantum
      calculations of 1H and 13C NMR chemical shifts and natural bonding orbital
      analysis.

PMID- 22615139
TI  - In vitro and in vivo toxicity of rinsed and aged nanocellulose-polypyrrole
      composites.
AB  - Novel composites of nanocellulose and the conducting polymer polypyrrole (PPy)
      are herein suggested as potential candidates for active ion-extraction membranes
      in electrochemically controlled hemodialysis. This study has defined processing
      parameters to obtain a biocompatible nanocellulose-PPy composite, and for the
      first time, the effect of the composite aging on cell viability has been studied.
      The influence of rinsing and extraction process steps, as well as aging under
      different conditions (i.e. in air, at -20 degrees C and in argon), on the
      electroactivity and cytotoxicity of a PPy-nanocellulose composite has been
      investigated. The biocompatibility evaluation was based on indirect toxicity
      assays with fibroblasts and monocyte cell lines and an acute toxicity test in
      mice, while the electroactivity was evaluated by cyclic voltammetry experiments.
      The as-prepared composite did not induce any cytotoxic response in vitro or in
      vivo. Extensive rinsing and 48 h incubation in biological buffer previous to the
      preparation of the culture medium extracts were, however, necessary to obtain a
      noncytotoxic composite. The as-prepared composite was also found to exhibit
      acceptable electrochemical performance, which was retained upon 4 weeks storage
      in argon atmosphere. It was shown that aging of the composite had a negative
      effect on biocompatibility, regardless of the storage condition. Thus, to allow
      for longtime storage of electroactive nanocellulose-PPy hemodialysis membranes,
      the degradation of PPy upon storage must be controlled. The present results show
      that the biocompatibility of PPy composites depends on the rinsing and
      pretreatment of the composite material as well as the aging of the material.

PMID- 22615141
TI  - Inhibitory control deficits in rats with ventral hippocampal lesions.
AB  - Two experiments are reported in which rats with selective hippocampal lesions
      were tested on 2 prefrontal-dependent tasks. In Experiment 1, we compared the
      effects of lesions of the ventral hippocampus (vHC), dorsal hippocampus (dHC),
      and sham control surgery on the 5-choice reaction time task. Whereas rats with
      lesions of the dHC were indistinguishable from sham controls, those with vHC
      lesions showed increased premature responses and reduced accuracy throughout the
      experiment. The subsequent administration of systemic escitalopram (5 mg/kg), a
      selective serotonin reuptake inhibitor, reduced the number of premature responses
      in the vHC animals to control levels. In contrast, systemic injections of GBR
      12909, a dopamine reuptake inhibitor, failed to ameliorate the impulsive deficit
      in the vHC group and, in addition, elevated perseverative responding in the vHC
      group only. In Experiment 2, we tested a separate group of rats with vHC lesions
      on a touchscreen visual discrimination and reversal learning task. Rats with vHC
      lesions acquired the visual discrimination as well as sham controls and showed
      normal inhibitory control of a previously reinforced response during reversal
      learning. These data support a role for the vHC in inhibitory control functions,
      especially in the inhibitory control of impulsive actions.

PMID- 22615140
TI  - HPS4/SABRE regulates plant responses to phosphate starvation through antagonistic
      interaction with ethylene signalling.
AB  - The phytohormone ethylene plays important roles in regulating plant responses to
      phosphate (Pi) starvation. To date, however, no molecular components have been
      identified that interact with ethylene signalling in regulating such responses.
      In this work, an Arabidopsis mutant, hps4, was characterized that exhibits
      enhanced responses to Pi starvation, including increased inhibition of primary
      root growth, enhanced expression of Pi starvation-induced genes, and
      overproduction of root-associated acid phosphatases. Molecular cloning indicated
      that hps4 is a new allele of SABRE, which was previously identified as an
      important regulator of cell expansion in Arabidopsis. HPS4/SABRE antagonistically
      interacts with ethylene signalling to regulate plant responses to Pi starvation.
      Furthermore, it is shown that Pi-starved hps4 mutants accumulate more auxin in
      their root tips than the wild type, which may explain the increased inhibition of
      their primary root growth when grown under Pi deficiency.

PMID- 22615142
TI  - Lower ligand denticity leading to improved thermodynamic and kinetic stability of
      the Gd3+ complex: the strange case of OBETA.
AB  - OBETA, OBETA, you bet: Thermodynamic and kinetic measurements show an apparent
      paradox. The stability of complexes of lanthanide trivalent ions is higher with
      the heptadentate ligand OBETA (ethylene glycol-bis(2-aminoethyl ether)-N,N,N',N'
      tetraacetic acid) than with its octadentate homologue EGTA (2,2'
      oxybis(ethylamine)-N,N,N',N'-tetraacetic acid). The unusual properties of
      Gd(OBETA)(-) (see structure), combined with the presence of two fast exchanging
      coordinated water molecules, candidates this complex as an MRI contrast agent.

PMID- 22615144
TI  - Calibration and limits of camera-based fluorescence correlation spectroscopy: a
      supported lipid bilayer study.
AB  - Camera-based fluorescence correlation spectroscopy (FCS) approaches allow the
      measurement of thousands of contiguous points yielding excellent statistics and
      details of sample structure. Imaging total internal reflection FCS (ITIR-FCS)
      provides these measurements on lipid membranes. Herein, we determine the
      influence of the point spread function (PSF) of the optical system, the laser
      power used, and the time resolution of the camera on the accuracy of diffusion
      coefficient and concentration measurements. We demonstrate that the PSF can be
      accurately determined by ITIR-FCS and that the laser power and time resolution
      can be varied over a wide range with limited influence on the measurement of the
      diffusion coefficient whereas the concentration measurements are sensitive to
      changes in the measurement parameters. One advantage of ITIR-FCS is that the
      measurement of the PSF has to be performed only once for a given optical setup,
      in contrast to confocal FCS in which calibrations have to be performed at least
      once per measurement day. Using optimized experimental conditions we provide
      diffusion coefficients for over ten different lipid membranes consisting of one,
      two and three constituents, measured in over 200,000 individual correlation
      functions. Using software binning and thus the inherent advantage of ITIR-FCS of
      providing multiple observation areas in a single measurement we test the FCS
      diffusion law and show how they can be complemented by the local information
      provided by the difference in cross-correlation functions (DeltaCCF). With the
      determination of the PSF by ITIR-FCS and the optimization of measurement
      conditions ITIR-FCS becomes a calibration-free method. This allows us to provide
      measurements of absolute diffusion coefficients for bilayers with different
      compositions, which were stable over many different bilayer preparations over a
      time of at least one year, using a single PSF calibration.

PMID- 22615143
TI  - Hydrogels for in vivo-like three-dimensional cellular studies.
AB  - Extensive efforts have been made to understand the effects of extracellular
      microenvironments on phenotypic activities for a wide array of stem, progenitor,
      and precursor cells. Hydrogels have emerged as invaluable platforms for examining
      the effects of extracellular matrix (ECM) properties on cell activities because
      of their several advantageous features. Specifically, hydrogels are unique
      materials that enable cell studies in three-dimensional (3D) environments,
      similar to in vivo environments. Recently, there have been increasing efforts to
      assemble cell-encapsulating hydrogels; however, hydrogel design strategies for 3D
      cell cultures have not been systematically discussed to date. Therefore, this
      review article summarizes current hydrogel designs for 3D cell culture studies
      and further discusses current challenges and potential resolutions for enhancing
      the controllability of hydrogel properties and microstructures. The hydrogels
      discussed herein include those of natural polymers (e.g., collagen, fibrinogen,
      alginate, and hyaluronic acids), synthetic polymers [e.g., poly(ethylene glycol)
      (PEG) and its derivatives], and mixtures of natural and synthetic polymers. We
      envision that hydrogels that enable 3D studies will greatly assist in the
      understanding of emergent cell behaviors, and ultimately become important
      biomedical tools for enhancing the quality of in vitro drug screening and
      clinical treatments.

PMID- 22615145
TI  - The ERalpha/ERbeta ratio determines oxidative stress in breast cancer cell lines
      in response to 17beta-estradiol.
AB  - The effects of 17beta-estradiol (E2) are mediated through activation of estrogen
      receptors (ER): ERalpha and ERbeta. It is known that ERalpha/ERbeta ratio is
      higher in breast tumors than in normal tissue. Since antioxidant enzymes and
      uncoupling proteins (UCPs) are reactive oxygen species (ROS) production and
      mitochondrial biogenesis regulators, our aim was to study the E2-effect on
      oxidative stress, antioxidant enzyme expression, and UCPs in breast cancer cell
      lines with different ERalpha/ERbeta ratios. The lower ERalpha/ERbeta ratio T47D
      cell line showed low ROS production and high UCP5 levels. However, the higher
      ERalpha/ERbeta ratio MCF-7 cell line showed an up-regulation of antioxidant
      enzymes and UCPs, yet exhibited high oxidative stress. As a result, a decrease in
      antioxidant enzyme activities and UCP2 protein levels, coupled with an increase
      in oxidative damage was found. On the whole, these results show different E2
      effects on oxidative stress regulation, modulating UCPs, and antioxidant enzymes,
      which were ERalpha/ERbeta ratio dependent in breast cancer cell lines.

PMID- 22615146
TI  - Stereospecificity of (1) H, (13) C and (15) N shielding constants in the isomers
      of methylglyoxal bisdimethylhydrazone: problem with configurational assignment
      based on (1) H chemical shifts.
AB  - In the (13) C NMR spectra of methylglyoxal bisdimethylhydrazone, the (13) C-5
      signal is shifted to higher frequencies, while the (13) C-6 signal is shifted to
      lower frequencies on going from the EE to ZE isomer following the trend found
      previously. Surprisingly, the (1) H-6 chemical shift and (1) J(C-6,H-6) coupling
      constant are noticeably larger in the ZE isomer than in the EE isomer, although
      the configuration around the -CH?N- bond does not change. This paradox can be
      rationalized by the C-H?N intramolecular hydrogen bond in the ZE isomer, which is
      found from the quantum-chemical calculations including Bader's quantum theory of
      atoms in molecules analysis. This hydrogen bond results in the increase of
      delta((1) H-6) and (1) J(C-6,H-6) parameters. The effect of the C-H?N hydrogen
      bond on the (1) H shielding and one-bond (13) C-(1) H coupling complicates the
      configurational assignment of the considered compound because of these spectral
      parameters. The (1) H, (13) C and (15) N chemical shifts of the 2- and 8-(CH(3)
      )(2) N groups attached to the -C(CH(3) )?N- and -CH?N- moieties, respectively,
      reveal pronounced difference. The ab initio calculations show that the 8-(CH(3)
      )(2) N group conjugate effectively with the pi-framework, and the 2-(CH(3) )(2) N
      group twisted out from the plane of the backbone and loses conjugation. As a
      result, the degree of charge transfer from the N-2- and N-8- nitrogen lone pairs
      to the pi-framework varies, which affects the (1) H, (13) C and (15) N
      shieldings.

PMID- 22615147
TI  - Further evidence on a role of chemokines in injury-related pain hypersensitivity:
      commentary on a paper by Saika et al. (2012, this issue).

PMID- 22615148
TI  - Short- and long-term peripheral nerve regeneration using a poly-lactic-co
      glycolic-acid scaffold containing nerve growth factor and glial cell line-derived
      neurotrophic factor releasing microspheres.
AB  - Addition of neural growth factors to bioengineered scaffolds may improve
      peripheral nerve regeneration. The aim of this study is to evaluate the short-
      and long term effect of microsphere delivered nerve growth factor (NGF) and glial
      cell derived neurotrophic factor (GDNF) in the 10 mm rat sciatic nerve gap.
      Eighty-four rats were assigned to seven groups (n = 6) at two endpoints (6 and 16
      weeks): saline, saline NGF, saline NGF-microspheres, saline GDNF, saline GDNF
      microspheres, saline blank microspheres, and autologous nerve graft. Total
      fascicular area and total number of myelinated fibers at mid-tube increased in
      all conduit groups between 6 and 16 weeks. Autologous, saline NGF-microsphere and
      saline GDNF-microsphere groups reached maximal histomorphometric values by 6
      weeks (p < 0.05). Compound muscle action potentials returned after 6 weeks for
      the autologous graft and continued to increase to a level of 3.6 +/- 1.9 mV at
      endpoint. No significant differences were found between study groups as measured
      by ankle angle. These experiments show an initial beneficial effect of
      incorporation of NGF- or GDNF-microspheres in a PLGA 85/15 nerve conduit, since
      histomorphometric values reached their maximum by 6 weeks compared to control
      groups. These results do not yet extrapolate into improved electrophysiological
      or functional improvement.

PMID- 22615149
TI  - Principles of management of thoracolumbar fractures.
AB  - There is little consensus on treatment of thoracolumbar fractures, which are one
      of the most controversial areas in spine surgery. The great variations in
      clinical decision making may come from differences in evaluation of spine
      stability with these fractures. Few high-quality studies concerning optimal
      treatment of thoracolumbar fractures have been conducted. This article reviews
      the conflicting results and recommendations for management of thoracolumbar
      fractures of currently published reports. Specifically, it addresses issues
      regarding evaluation of stability, indications for operative treatment, timing of
      surgery, surgical approach, and fusion length.

PMID- 22615150
TI  - Factors influencing segmental lumbar lordosis after lateral transpsoas interbody
      fusion.
AB  - OBJECTIVE: Although contributions to sagittal alignment have been characterized
      for anterior, posterior and transforaminal lumbar interbody fusion, sagittal
      alignment after lateral transpsoas interbody fusion (LTIF) has not yet been
      characterized. This study examined the ability of LTIF to restore lumbar lordosis
      and identified factors associated with change in sagittal alignment. METHODS:
      Twenty-nine patients and 67 levels were studied. Segmental lordosis, anterior
      posterior cage position, and cage obliquity were measured on preoperative and
      postoperative radiographs and CT scans. Change in sagittal alignment was analyzed
      with respect to demographic information and measures of cage position and
      obliquity to identify factors associated with segmental alignment change.
      RESULTS: Mean lordosis increased 3.7 degrees  at instrumented segments,
      increasing from 4.1 degrees  preoperatively to 7.8 degrees  postoperatively.
      Although increases at each level were significant, there were no significant
      differences between levels. Lordosis increase was inversely-associated with
      preoperative lordosis; levels with the least preoperative lordosis gained the
      most lordosis. Cage obliquity and height were not significantly associated with
      lordosis change. Anterior cage placement resulted in the largest lordosis gain
      (+7.4 degrees /level) while posterior placement was prokyphotic (-1.2 degrees
      /level). There were no significant associations with age, sex or body mass index.
      CONCLUSION: Anteroposterior cage placement is an important intraoperative
      determinant of postoperative alignment; anterior placement results in greater
      lordosis while middle/posterior placement has a minimal effect on sagittal
      alignment.

PMID- 22615151
TI  - Management of giant cell tumor of bone: computerized tomography based selection
      strategy and approaching the lesion through the site of cortical break.
AB  - OBJECTIVE: A retrospective study was carried out in patients with giant cell
      tumor of bone to compare the functional and radiographic outcome of curettage and
      bone grafting using a novel CT based selection strategy to that of patients of a
      similar age treated with anatomic/standard curettage and bone grafting. METHODS:
      Curettage and bone grafting after CT classification was performed in 31 patients
      and curettage and bone grafting without CT classification in 20. The surgical
      approach for curettage in the CT classified group of patients was through the
      site of the cortical break, irrespective of the standard approach to the
      particular region of bone involved. The aim of this approach was to achieve wide
      excision of the possibly involved soft tissue. RESULTS: At similar duration of
      follow up (72 months) in patients with a similar mean age (33 years),
      Musculoskeletal Tumor Society (MSTS) scores for CT classified patients were
      similar to those of patients who had undergone standard curettage. However, the
      postoperative recurrence rate in the CT classified group was significantly less
      (12.9%) than in the non-CT classified group. CONCLUSION: A CT based selection
      strategy is a valid preoperative tool for evaluation of giant cell tumor.
      Further, for curettage these lesions are better approached through the site of
      cortical break, irrespective of standard approaches, so that adequate soft tissue
      clearance can be achieved.

PMID- 22615152
TI  - Medial patellar retinaculum plasty versus medial capsule reefing for patellar
      subluxation in adult.
AB  - OBJECTIVE: The purpose of this study was to evaluate the clinical and functional
      results of surgical treatment for patellar subluxation. METHODS: A retrospective
      study was undertaken between October 2004 and April 2009 of 78 cases of patellar
      subluxation: 40 cases with medial capsule reefing, of which 15 cases had the
      combination of lateral retinacular release (Group A); and 38 cases with medial
      patellar retinaculum plasty, of which 12 cases had the combination of lateral
      retinacular release (Group B). All patients had CT scans available for reviewing
      congruence angle (CA) with knee flexion at 30 degrees. In addition, knee function
      was evaluated using the Kujala score and subjective questionnaires. RESULTS:
      Patients were followed up for a mean 60 months (33-87 months). The Kujala score
      improved significantly from 78.3 +/- 1.0 to 88.3 +/- 1.6 in Group A and from 77.8
      +/- 0.9 to 91.2 +/- 1.7 in Group B (P < 0.05). Postoperatively, the CA on CT scan
      had a statistical difference between the two groups (P < 0.05). The subjective
      questionnaire revealed a significant difference (P < 0.05), including 12
      excellent, 20 good and eight fair in Group A, and 25 excellent, and 13 good in
      Group B. CONCLUSION: The medial retinaculum plasty was better than medial capsule
      reefing in improving the subjective effects and decreasing the patellar
      subluxation rate.

PMID- 22615153
TI  - Unstable trochanteric fractures in elderly osteoporotic patients: role of primary
      hemiarthroplasty.
AB  - OBJECTIVE: Unstable intertrochanteric fractures in osteoporotic patients are
      difficult to treat. Fixation failure often leads to prolonged morbidity and poor
      functional outcomes. The objective of the present study was to investigate
      primary replacement as a suitable option that could minimize complications in
      selected patients. METHODS: From January 2004 to March 2007, 28 elderly
      osteoporotic patients with unstable intertrochanteric fractures were included in
      this study. Their fractures were classified according to the AO/OTA
      classification (8 patients, 31A2.2; 17 patients, 31A2.3 and 3 patients, 31A3.3)
      and their osteoporosis was confirmed by bone densitometry. Hemiarthroplasty was
      performed in all patients and the outcomes analyzed using the Harris hip score
      system. RESULTS: Of the 28 patients, 19 were women and the mean age was 79 years
      (range, 52-95 years). At a mean follow up of 4.2 years (range, 3-6 years), there
      were 17 excellent, 7 good, 2 fair and 2 poor results according to the Harris hip
      score system. CONCLUSION: In elderly osteoporotic patients with unstable
      intertrochanteric fractures, hemiarthroplasty is a reliable alternative to
      internal fixation. The functional outcome has been encouraging and we suggest it
      as a method of treatment in this group of patients.

PMID- 22615154
TI  - Motion analysis of single-level cervical total disc arthroplasty: a meta
      analysis.
AB  - OBJECTIVE: The purpose of this review was to investigate whether cervical total
      disc arthroplasty (CTDA) preserves motion of the treated level and what its
      effect is on adjacent segments. METHODS: Relevant published reports were
      collected from PubMed, Medline and Cochrane library. The original studies were
      considered eligible only if the range of motion (ROM) of the index or adjacent
      level had been investigated. A meta-analysis was then performed on the collected
      data. Statistical heterogeneity across the various trials was tested using
      Cochran's Q statistic and I (2) ; in the case of heterogeneity, a random effect
      model was used. RESULTS: The weighted mean differences (WMDs) of the index level
      were 0.34 (95% confidence interval [CI], -0.53~1.21, P = 0.440) and 0.23 (95% CI,
      -1.92~2.38, P = 0.834) in all included studies and randomized control trials
      (RCTs), respectively. The WMDs of the cranial adjacent levels, caudal adjacent
      levels and whole cervical spines were 1.01 (95% CI, 0.55~1.47, P = 0.000), 1.10
      (95% CI, 0.61~1.59, P = 0.000) and 3.40 (95% CI, -6.02~12.82, P = 0.479),
      respectively. CONCLUSION: These findings suggest that the protective effect
      against adjacent segment degeneration provided by cervical arthroplasty might not
      be as good as has been believed. Long-term supporting evidence is still needed.

PMID- 22615155
TI  - Effect of pregnancy and obesity on arch of foot.
AB  - OBJECTIVE: Endocrine changes occurring during pregnancy result in increased
      laxity of the ligaments of the foot. This may lead to gradual collapse of the
      foot arches. The aim of the study was to determine whether pregnancy and body
      mass index (BMI) had a role in affecting the foot arches at long term. METHODS: A
      collapsed arch results in widening of the feet, thus altering the foot size. The
      control group included nulliparous women, while the study group included women
      who had been pregnant at least once. The groups were stratified secondarily by
      obesity according to BMI. We reviewed over 1000 charts at the outpatient offices
      in a large Mid-Western city. The age, BMI, and shoe size in an athletic shoe were
      recorded. RESULTS: There were 40 subjects in the control group and 70 in the
      study group. 19/40 women in control and 46/70 in study group experienced a change
      in shoe size (P = 0.06). Of those affected, the non-obese control group
      experienced a 9.7% change in shoe size while the obese study group experienced a
      15.5% change (P < 0.05). CONCLUSION: There was neither a change in size between
      women who had been pregnant and the nulliparous, nor was there a difference
      between the obese and non-obese. However, there was a statically significant
      difference between those affected who were both non-obese and nulliparous and
      those who had been pregnant and who are obese. Individually, the effect of
      pregnancy and BMI are highly suggestive and clinically relevant.

PMID- 22615156
TI  - Slope on proximal tibiofibular articular surface with 3-D reconstruction by 64
      slice computed tomography on human.
AB  - OBJECTIVE: Using 64-slice spiral CT to reconstruct virtual knee joints of adults,
      we measured the gradient of proximal tibia-fibular joint and compared this result
      with bare joint measurement. We then discuss the accuracy of these measurements
      using a 64-slice spiral CT. METHODS: Two hundred healthy adults were selected,
      including 100 males and 100 females, aged from 18 to 90 years. The gradient of
      the longitudinal axis of the fibula and the articular surface, and the angle of
      horizon of the proximal tibia-fibular articular surface and the horizontal line
      were measured by using a 64-slice spiral CT scan. RESULTS: The angle between the
      longitudinal axis of the fibula and the articular surface (angle A) was 56.80
      degrees  +/- 6.59 degrees , both the left and the right fibula showed no
      significant difference (t = 0.308, P = 0.758). The angle between horizontal line
      and the articular surface (angle B) was 32.80 degrees  +/- 6.49 degrees . The
      regression or correlation analysis findings showed that there is a negative
      relationship (r = -0.952, P = 0.000), and there is significant difference (t =
      51.87, P < 0.01) between the angle A and the angle B. CONCLUSION: The measurement
      value of using 64-slice spiral CT to reconstruct the slope of proximal tibia
      fibular joints has no difference compared to the measurement value of the slope
      of bare proximal tibia-fibular joints. It is a precise, convenient method and is
      easy to apply for clinical study.

PMID- 22615157
TI  - Artrhoscopic rotator cuff repair with augmentation: the V-sled technique.
AB  - Numerous techniques have been described for patch positioning in rotator cuff
      shoulder arthroscopic surgery. These techniques seem to be difficult challenges
      for the majority of arthroscopic surgeons, and because of that they are called
      "highly demanding" techniques. Without the use of dedicated instruments and
      cannulas, the authors propose a V-sled technique that seems to be more
      reproducible, quicker and less difficult to perform for arthroscopic shoulder
      surgeons. The patient is placed in the lateral position. All arthroscopic
      procedures are performed without the use of cannulas. The standard posterior
      portal is used for the glenohumeral (GH) joint arthroscopy with fluid inflowing
      through the scope. After an accurate evaluation of the GH space, the scope is
      then introduced into the subacromial space. With the use of a spinal needle, a
      lateral portal is performed. The great tuberosity is prepared with a bur to place
      two 5.5 mm triple-loaded radiolucent anchors. In addition, two free high strength
      sutures are passed through the muscle, respectively. The repair is performed
      using two high strength sutures from each anchor. The third wire from each anchor
      is retrieved out of the accessories portals used for the insertion of the
      anchors. In addition, two free high strength sutures are passed through the
      muscle, and the patch sizing is done using a measuring probe introduced through
      the lateral portal. Next, the patch is then prepared and is introduced into the
      subacromial space, and then the patch is stabilized, and the free sutures are
      tied.

PMID- 22615158
TI  - Bone delivers its energy information to fat and islets through osteocalcin.
AB  - Bone has emerged as a novel endocrine organ for its ability to produce hormones
      and involvement in several regulatory feedback loops. Osteocalcin (OCN) is
      released into bloodstream during bone resorption and has been demonstrated to
      exert endocrine regulation on islets, fat and male testis to form feedback loops.
      We hypothesize that bone delivers its energy metabolism signals to related energy
      regulating organs through OCN based on the following evidence: First, OCN has
      close interactions with islets and fat, and it shows ability to stimulate islets
      and fat to secret insulin and adiponectin, respectively. Islets and fat are
      important organs involved in energy metabolism. Second, OCN undergoes
      physiological fluctuations during a lifetime. In children and adolescents, during
      the development of osteoporosis or after bone fracture, OCN level increases
      significantly. The elevated OCN at these stages represents enhanced bone turnover
      and metabolic activity, which require more energy supply. Therefore, the
      metabolic activity of bone and the energy-related organs like fat and islets are
      closely linked by circulating OCN. Through systemic release of OCN, bone delivers
      its energy-demanding information to other organs to satisfy its energy
      requirement.

PMID- 22615159
TI  - Spontaneous rupture of multiple extensor tendons following repeated steroid
      injections: a case report.

PMID- 22615160
TI  - Knee melorheostosis treated by drilling fenestration: a case report.

PMID- 22615161
TI  - Neutral and anionic guests and their effect on the formation of pseudorotaxanes
      by using a flexible tetracationic imidazolium macrocycle.
AB  - The ability to control and direct molecular assembly has important implications
      in the design of environmentally responsive materials. Reported here is the use
      of competitive neutral- and anionic-guest recognition to control the formation,
      disruption, replacement-based construction and higher-order assembly properties
      of pseudorotaxane structures involving a large, cationic tetraimidazolium
      receptor. In particular, we showed that the chloride anion (as the
      tetrabutylammonium (TBA(+)) salt) serves to replace directly the 2,6-naphthalene
      dicarboxylate dianion from the preformed complex, involving this dianion. In
      contrast, the addition of the nitrate anion (as the TBA(+) salt) serves to effect
      displacement of a pre-bound 2,6-naphthalene dicarboxylate dianion in a stepwise
      manner allowing for stabilization of a so-called "outside"-binding mode under
      appropriate conditions. We have also found that by using biphenyl-3,4,3',4'
      tetraamine as the guest, a 1D-donor-acceptor-donor coordination polymer can be
      stabilized, whereas the addition of 6-amino-naphthalene-2-sulfonate anion to the
      pre-formed complex between the tetraimidazolium receptor and the 2,6-naphthalene
      dicarboxylate dianion produces a new pseudorotaxane complex. This guest-based
      competition and subsequent molecular translocation is supported by solution-state
      NMR spectroscopic studies as well as solid-state single-crystal X-ray structural
      analyses. The results described herein provide initial evidence that guest
      competition can be used to control molecular "switching" and substrate binding
      within an appropriately designed anion receptor.

PMID- 22615162
TI  - FLOCK provides reliable solutions to the "number of populations" problem.
AB  - Identifying groups of individuals forming coherent genetic clusters is relevant
      to many fields of biology. This paper addresses the K-partition problem: given a
      collection of genotypes, partition those genotypes into K groups, each group
      being a sample of the K source populations that are represented in the collection
      of genotypes. This problem involves allocating genotypes to genetic groups while
      building those groups at the same time without the use of any other a priori
      information. FLOCK is a non-Markov chain Monte Carlo (MCMC) algorithm that uses
      an iterative method to partition a collection of genotypes into k groups. Rules
      to estimate K are formulated and their validity firmly established by running
      simulations under several migration rates, migration regimes, number of loci, and
      values of K. FLOCK tended to build clusters largely consistent with the source
      samples. The performance of FLOCK was also compared with that of STRUCTURE and
      BAPS. FLOCK provided more accurate allocations to clusters and more reliable
      estimates of K; it also ran much faster than STRUCTURE. FLOCK is based on an
      entirely novel approach and provides a true alternative to the existing, MCMC
      based, algorithms. FLOCK v.2.0 for microsatellites or for AFLP markers can be
      downloaded from
      http://www.bio.ulaval.ca/no_cache/departement/professeurs/fiche_des_professeurs/p
      ofesseur/11/13/.

PMID- 22615163
TI  - Flexibility and applicability of beta-expectation tolerance interval approach to
      assess the fitness of purpose of pharmaceutical analytical methods.
AB  - An innovative versatile strategy using Total Error has been proposed to decide
      about the method's validity that controls the risk of accepting an unsuitable
      assay together with the ability to predict the reliability of future results.
      This strategy is based on the simultaneous combination of systematic (bias) and
      random (imprecision) error of analytical methods. Using validation standards,
      both types of error are combined through the use of a prediction interval or beta
      expectation tolerance interval. Finally, an accuracy profile is built by
      connecting, on one hand all the upper tolerance limits, and on the other hand all
      the lower tolerance limits. This profile combined with pre-specified acceptance
      limits allows the evaluation of the validity of any quantitative analytical
      method and thus their fitness for their intended purpose. In this work, the
      approach of accuracy profile was evaluated on several types of analytical methods
      encountered in the pharmaceutical industrial field and also covering different
      pharmaceutical matrices. The four studied examples depicted the flexibility and
      applicability of this approach for different matrices ranging from tablets to
      syrups, different techniques such as liquid chromatography, or UV
      spectrophotometry, and for different categories of assays commonly encountered in
      the pharmaceutical industry i.e. content assays, dissolution assays, and
      quantitative impurity assays. The accuracy profile approach assesses the fitness
      of purpose of these methods for their future routine application. It also allows
      the selection of the most suitable calibration curve, the adequate evaluation of
      a potential matrix effect and propose efficient solution and the correct
      definition of the limits of quantification of the studied analytical procedures.

PMID- 22615164
TI  - Comparative cellular and molecular analyses of pooled bone marrow multipotent
      mesenchymal stromal cells during continuous passaging and after successive
      cryopreservation.
AB  - The clinical application of human bone marrow derived multipotent mesenchymal
      stromal cells (MSC) requires expansion, cryopreservation, and transportation from
      the laboratory to the site of cell implantation. The cryopreservation and thawing
      process of MSCs may have important effects on the viability, growth
      characteristics and functionality of these cells both in vitro and in vivo. More
      importantly, MSCs after two rounds of cryopreservation have not been as well
      characterized as fresh MSCs from the transplantation perspective. The objective
      of this study was to determine if the effect of successive cryopreservation of
      pooled MSCs during the exponential growth phase could impair their morphology,
      phenotype, gene expression, and differentiation capabilities. MSCs cryopreserved
      at passage 3 (cell bank) were thawed and expanded up to passage 4 and
      cryopreserved for the second time. These cells (passive) were then thawed and
      cultured up to passage 6, and, at each passage MSCs were characterized. As
      control, pooled passage 3 cells (active) after one round of cryopreservation were
      taken all the way to passage 6 without cryopreservation. We determined the growth
      rate of MSCs for both culture conditions in terms of population doubling number
      (PDN) and population doubling time (PDT). Gene expression profiles for
      pluripotency markers and tissue specific markers corresponding to neuroectoderm,
      mesoderm and endoderm lineages were also analyzed for active and passive cultures
      of MSC. The results show that in both culture conditions, MSCs exhibited similar
      growth properties, phenotypes and gene expression patterns as well as similar
      differentiation potential to osteo-, chondro-, and adipo-lineages in vitro. To
      conclude, it appears that successive or multiple rounds of cryopreservation of
      MSCs did not alter the fundamental characteristics of these cells and may be used
      for clinical therapy.

PMID- 22615165
TI  - Low-temperature route to crystalline titania network structures in thin films.
AB  - A low temperature route to crystalline titania nanostructures in thin films is
      presented. The synthesis is performed by the combination of sol-gel processes,
      using a novel precursor for this kind of application, an ethylene glycol-modified
      titanate (EGMT), and the structure templating by micro-phase separation of a di
      block copolymer. Different temperatures around 100  degrees C are investigated.
      The nanostructure morphology is examined with scanning electron microscopy,
      whereas the crystal structure and thin film compositions are examined by
      scattering methods. Optoelectronic measurements reveal the band-gap energies and
      sub-band states of the titania films. An optimum titania thin film is created at
      temperatures not higher than 90  degrees C, regarding sponge-like morphology with
      pore sizes of 25-30 nm, porosity of up to 71% near the sample surface, and
      crystallinity of titania in the rutile phase. The low temperature during
      synthesis is of high importance for photovoltaic applications and renders the
      resulting titania films interesting for future energy solutions.

PMID- 22615170
TI  - Kinetics of iterative carbohydrate transfer to polysaccharide catalyzed by
      chondroitin polymerase on a highly sensitive flow-type 27 MHz quartz-crystal
      microbalance.
AB  - Using a highly sensitive flow-type 27 MHz quartz crystal microbalance, we could
      detect a small mass change during stepwise and alternating one-sugar transfer of
      glucuronic acid (GlcA) and N-acetylgalactosamine (GalNAc) to an acceptor,
      catalyzed by chondroitin polymerase from Escherichia coli strain K4 (K4CP), and
      analyze the elongation mechanism of K4CP. K4CP was found to bind strongly to a
      chondroitin acceptor (K(d)=0.97 MUM). Although the binding affinity and the
      catalytic rate constant for each monomer were considerably different, the
      apparent catalytic efficiency (k(cat)/K(m)) was similar (6.3*10(4)  M(-1)  s(-1)
      for GlcA transfer and 3.4*10(4)  M(-1)  s(-1) for the GalNAc transfer). This is
      reasonable for the smooth alternating elongation of GlcA and GalNAc on the
      acceptor. This is the first study to report the determination of kinetic
      parameters for enzymatic, alternated, sugar elongation.

PMID- 22615169
TI  - Orthopedic implant cobalt-alloy particles produce greater toxicity and
      inflammatory cytokines than titanium alloy and zirconium alloy-based particles in
      vitro, in human osteoblasts, fibroblasts, and macrophages.
AB  - The performance of total joint arthroplasty (TJA) depends on the size/shape,
      material, and amounts of implant debris. Much remains unknown in terms of which
      types of debris are most reactive. We compared the responses of human periimplant
      cells, osteoblasts, fibroblasts, and macrophages, exposed to particles of
      different metal-based particles (i.e., cobalt-chromium-molybdenum (CoCrMo) alloy,
      titanium (Ti) alloy, zirconium (Zr) oxide, and Zr alloy. CoCrMo-alloy particles
      were by far the most toxic (p < 0.05) and decreased viability and proliferation
      of human osteoblasts, fibroblasts, and macrophages by >50% at a dose of only 50
      particles per cell. All particle types induced the production of interleukin (IL)
      6, tumor necrosis factor (TNF)-alpha, and IL-8 by osteoblasts, fibroblasts, and
      monocytes/macrophages. However, the greatest cytokine responses of macrophages
      were to CoCrMo alloy (TNF-alpha and IL-8) and Ti alloy (IL-1beta). Likewise, the
      greatest responses of fibroblasts and osteoblasts were to CoCrMo alloy (IL-6 and
      TNF-alpha) (i.e., IL-6 300 pg/mL; 30-fold max, TNF-alpha 150 pg/mL; 15-fold max)
      versus controls. For macrophages, CoCrMo particles induced IL-8 (> 2000 pg/mL;
      approx 100-fold max) above controls and were also significantly elevated above
      levels produced by Zr-based particles. Submicron sized (0.2-0.9 MUm) Zr-based
      particles (originally presumed to be more reactive) induced less toxicity and
      inflammatory responses when compared with larger (approx 1 MUm) CoCrMo-alloy and
      Ti-alloy particles.

PMID- 22615171
TI  - Exhaled breath condensate purines correlate with lung function in infants and
      preschoolers.
AB  - RATIONALE: Although airway inflammation begins early in life in children with
      chronic respiratory diseases, current methods to assess this inflammation are
      invasive and entail significant risk. Measurement of exhaled breath condensate
      (EBC) purines and other biomarkers offers a less invasive method to assess airway
      inflammation; however, the feasibility and utility of EBC biomarkers in young
      children has not been established. METHODS: EBC was collected from children <3
      years old with cystic fibrosis or other lung diseases during clinically indicated
      infant pulmonary function tests (iPFTs). EBC concentrations of the purine
      biomarkers adenosine (Ado), adenosine monophosphate (AMP), and the dilution
      marker urea were measured using mass spectrometry. RESULTS: EBC was successfully
      collected (average volume 330 +/- 170 ul) from preschool children (age 2.3 +/-
      0.8 years) in 15 of 17 iPFTs. No significant changes in oxygen saturation (96.9
      +/- 1.6 start, 96.8 +/- 1.7 end, P = 0.389) or respiratory rate (35.2 +/- 7.5
      start, 34.6 +/- 7.9 end, P = 0.443) were observed during collection. Ado and AMP
      were successfully measured in 13/15 samples [8 cystic fibrosis (CF)]. EBC AMP to
      Ado ratio (AMP/Ado) negatively correlated with forced expiratory volume at 0.5
      sec (FEV(0.5) , r = -0.71, P < 0.01) and positively with the ratio of residual
      volume to total lung capacity (RV/TLC, r = 0.66, P = 0.015). These correlations
      remained statistically significant in the subset with CF. CONCLUSIONS: EBC can be
      safely collected and analyzed in preschool children using commercially available
      equipment. The EBC AMP/Ado ratio correlates with measures of infant lung function
      and may be a less invasive means of monitoring airway inflammation in this
      population.

PMID- 22615172
TI  - Divalent europium nanocrystals: controllable synthesis, properties, and
      applications.
AB  - Magnetic and luminescent bifunctional divalent europium nanocrystals (Eu(2+) 
      NCs) are a promising class of novel advanced materials that have various
      applications in magneto-optic devices, catalysis, bioimaging, and solar cells. In
      the past few decades, much work has been carried out to study the synthesis,
      properties, and applications of Eu(2+)  NCs. The aim of this Minireview is to
      present the progress in preparing Eu(2+)  NCs based on the reported research, by
      describing the advantages and disadvantages of the synthesis methods. The
      morphologies and size are controlled through adjusting the experimental
      conditions. Eu(2+)  NCs show superior magnetic and luminescence properties
      simultaneously. Self-assembly and doping with other ions are important routes to
      improve their magnetic and luminescence properties. Their applications in magneto
      optic devices are discussed. Some difficulties and challenges in the fabrication
      of Eu(2+)  NCs are discussed, such as water-soluble Eu(2+)  NCs and tunable
      luminescence in the whole visible region.

PMID- 22615173
TI  - Leukemia/lymphoma-related factor regulates oligodendrocyte lineage cell
      differentiation in developing white matter.
AB  - Leukemia/lymphoma-related factor (LRF) is a zinc-finger transcription factor that
      regulates differentiation and oncogenesis in multiple tissues and cell lineages.
      The potential role for LRF in cells of the CNS has not been examined to date.
      This study shows prominent nuclear expression of LRF in diverse neuronal
      populations and in oligodendrocytes. We focused on examining the function of LRF
      during the transition from oligodendrocyte progenitor (OP) to mature
      oligodendrocyte that is associated with myelination in the postnatal spinal cord.
      During spinal cord myelination, LRF is expressed in only a minority of OP cells
      whereas most mature oligodendrocytes exhibited nuclear LRF immunoreactivity. Mice
      with floxed alleles of the Zbtb7a gene, which encodes for LRF protein, were used
      for in vivo analysis of LRF function. Lentiviral driven Cre recombinase
      inactivation of LRF at postnatal day 7 reduced the proportion of OP cells that
      differentiated into mature oligodendrocytes by postnatal day 28. Astrocyte
      populations were not altered by LRF deletion in the same tissues. These results
      indicate that LRF deletion reduces differentiation within the oligodendrocyte
      lineage and does not alter OP lineage choice. In vitro analysis confirmed a
      specific effect of LRF on OP differentiation. In neonatal OP cultures, RNA
      interference targeting LRF inhibited OP differentiation while LRF transduction
      was sufficient to induce differentiation into oligodendrocytes. These results
      support a critical role for LRF in transcriptional control of differentiation in
      oligodendrocyte lineage cells during developmental myelination in the CNS.

PMID- 22615174
TI  - An electron paramagnetic resonance spectroscopic investigation on the growth
      mechanism of NaYF4:Gd nanocrystals.
AB  - Doped nanocrystals of NaYF(4) and NaGdF(4) are currently studied as upconversion
      luminescence markers and magnetic resonance imaging contrast agents. An EPR
      investigation on the growth mechanism of NaYF(4):Gd and NaGdF(4) nanocrystals
      showed that these nanomaterials grow in the standard oleic acid-based reaction
      medium by a dissolution/recrystallization mechanism and not by the aggregation or
      oriented attachment of smaller particles.

PMID- 22615175
TI  - Effects of microrough and hierarchical hybrid micro/nanorough surface implants on
      osseointegration in ovariectomized rats: A longitudinal in vivo microcomputed
      tomography evaluation.
AB  - This study aimed to evaluate the effects of microrough and hierarchical hybrid
      micro/nanorough surface implants on osseointegration in ovariectomized rats at
      different time points. Implants with machined, microrough and hierarchical hybrid
      micro/nanorough surfaces were inserted into the distal femurs of ovariectomized
      Sprague-Dawley female rats. At weeks 0, 4, and 12 following implantation, in vivo
      microcomputed tomography (micro-CT) scanning was used to assess bone
      microarchitectural changes. After 12 weeks, all the rats were sacrificed, and the
      femurs with implants were harvested for histological analysis and pull-out test.
      For the Micro-CT analysis, the trabecular number and the bone volume ratio
      increased significantly in the microrough group (p < 0.01) and micro/nanorough
      group (p < 0.01) compared with the machined group. The trabecular separation
      decreased significantly in the micro/nanorough group (p < 0.01) compared with the
      other two groups. For the maximum pull-out forces and the bone-implant-contact
      analyses, significant statistical differences were found among the three groups,
      with the following sequence: micro/nanorough group > microrough group > machined
      group. The results indicate that the microrough and the hierarchical hybrid
      micro/nanorough surfaces of the implant can be beneficial to osseointegration
      under osteoporotic conditions, and the hierarchical hybrid micro/nanorough
      surface is more efficient.

PMID- 22615176
TI  - 3D cell culture systems--towards primary drug discovery platforms: an interview
      with Heinz Ruffner (Novartis) and Jan Lichtenberg (InSphero).
AB  - Advanced cell culture systems for regenerative medicine, drug efficacy and
      toxicity testing, enabling technologies to create and analyze 3D cell culture
      systems were the topics of the 3D cell culture meeting taking place in March 14
      16, 2012 at the Technopark in Zurich, Switzerland. At this meeting Biotechnology
      Journal had the pleasure to talk to Dr. Heinz Ruffner, Novartis AG, and Dr. Jan
      Lichtenberg, co-founder and CEO of InSphero AG, about challenges and perspectives
      in using 3D cell culture systems as primary drug discovery platforms.

PMID- 22615177
TI  - Nanofusion: mesoporous zeolites made easy.
AB  - A new path to zeolites: Nanofusion is a template-free, one-step process that
      gives mesoporous zeolite beta with tunable mesopore diameters in very short
      reaction times. The hierarchical materials are built from zeolite beta
      nanocrystals in concentrated gels. The nanocrystals can either be retrieved as
      individual particles in a colloidal suspension or are directly fused into
      mesoporous zeolitic materials (see scheme).

PMID- 22615178
TI  - Cycle ergometer tests in children with cystic fibrosis: reliability and
      feasibility.
AB  - The aim of this study was to assess the reliability and feasibility of cycle
      ergometer tests in young children with cystic fibrosis (CF). Children with CF
      aged 6-11 years and with stable lung disease performed two cycle ergometry tests
      (intermittent sprint and continuous incremental) on two occasions 1 week apart.
      Reliability was assessed using repeated-measures ANOVA. Bias was considered to be
      significant at P < 0.05 level and a coefficient of variation (CV) below 10% was
      considered acceptable. Feasibility and acceptability data were also collected.
      Sixteen children with CF completed the study: (9M:7F), 8.7(1.8) years, FEV(1)
      %predicted: 88.1(17.4). Power measurements recorded during the intermittent
      sprint test demonstrated significant bias over days (P < 0.05) and CVs were
      between 10% and 15%. Peak work capacity recorded during the continuous
      incremental test was reliable (bias P < 0.05, CV < 10%), as was heart rate and
      SpO(2) recorded during both tests (bias P < 0.05, CV < 10%). No problems were
      experienced in administering the tests and all children completed both tests on
      two separate occasions. There was a mixed response to questions on acceptability
      of tests. This is the first study to provide information on the reliability of
      performance measures recorded during an intermittent sprint protocol (peak power)
      and a continuous incremental cycle ergometry (peak work capacity) in children
      with CF.

PMID- 22615179
TI  - Calixarene-based surfactants: conformational-dependent solvation shells for the
      alkyl chains.
AB  - Thermodynamic parameters obtained from studying the micellization of amphiphilic
      p-sulfonatocalix[n]arenes were correlated with the alkyl chain length and with
      the number of monomeric units (n) in the calix[n]arene structure. The
      micellization Gibbs free energy (DeltaG(M)(o)) becomes more negative upon
      increasing the alkyl chain length of the p-sulfonatocalix[4]arene. This is in
      agreement with the trend generally observed for other surfactants. However, the
      DeltaG(M)(o) value for transferring one CH(2) group from the bulk aqueous medium
      to the micelle [DeltaG(M)(o)(CH(2))] is lower than the value generally observed
      for single-chain surfactants, suggesting the existence of intramolecular
      interactions between the alkyl chains of the free unimers. On the other hand, the
      critical micelle concentration (cmc; per alkyl chain unit) increased with the
      increasing number of monomeric units. These results are explained on the basis of
      the conformation adopted by the calixarene in the bulk solution. The
      calix[4]arene derivatives are preorganized into the cone conformation, which is
      favorable for the formation of globular aggregates. The calix[6]arene and
      calix[8]arene derivatives do not adopt cone conformations. Changing these
      conformations to the more favorable cone conformer in the aggregates implies an
      energetic cost that contributes to making DeltaG(M)(o) less efficient. In the
      case of the calix[6]arene derivative this energetic cost is enthalpic, whereas in
      the case of the octamer it is both enthalpic and entropic. Both the
      DeltaG(M)(o)(CH(2)) value and the change in heat capacity (DeltaCp(M)(o)) seem to
      indicate that for the cone calix[4]arene derivatives all alkyl chains are
      solvated by the same hydration shell, whereas in the case of the highly flexible
      calix[8]arene derivative each alkyl chain is individually hydrated.

PMID- 22615181
TI  - Structure formation and catalytic activity of DNA dissolved in organic solvents.
AB  - Equal-opportunity dissolver: By attaching polyethylene glycol at its 5' end, DNA
      (PEG-DNA) can be solubilized in various organic solvents and was shown to form G
      quadruplexes by CD spectroscopy. A complex containing iron(III) protoporphyrin IX
      (hemin) and G-quadruplex-forming PEG-DNA catalyzed an oxidative reaction in
      methanol (see scheme).

PMID- 22615180
TI  - Molecular imaging of microglia/macrophages in the brain.
AB  - Neuroinflammation perpetuates neuronal damage in many neurological disorders.
      Activation of resident microglia and infiltration of monocytes/macrophages
      contributes to neuronal injury and synaptic damage. Noninvasive imaging of these
      cells in vivo provides a means to monitor progression of disease as well as
      assess efficacies of potential therapeutics. This review provides an overview of
      positron emission tomography (PET) and magnetic resonance (MR) imaging of
      microglia/macrophages in the brain. We describe the rationale behind PET imaging
      of microglia/macrophages with ligands that bind to translocator protein-18 kDa
      (TSPO). We discuss the prototype TSPO radioligand [(11)C]PK11195, its
      limitations, and the development of newer TSPO ligands as PET imaging agents. PET
      imaging agents for targets other than TSPO are emerging, and we outline the
      potential of these agents for imaging brain microglia/macrophage activity in
      vivo. Finally, we briefly summarize advances in MR imaging of
      microglia/macrophages using iron oxide nanoparticles and ultra-small super
      paramagnetic particles that are phagocytosed. Despite many technical advances,
      more sensitive agents are required to be useful indicators of neuroinflammation
      in brain.

PMID- 22615183
TI  - Synthesis of a heparan sulfate mimetic library targeting FGF and VEGF via click
      chemistry on a monosaccharide template.
AB  - A disulfated methyl 6-azido-6-deoxy-alpha-D-mannopyranoside template was used as
      a core structure for binding to the angiogenic growth factors FGF-1, FGF-2, and
      VEGF. The core structure was diversified in a rapid, parallel manner by employing
      the Cu(I)-catalyzed Huisgen azide-alkyne cycloaddition ("click") reaction. The
      diversity was further extended by incorporating a Swern oxidation-Wittig reaction
      sequence on a click adduct of propargyl alcohol. Thus, the sulfated core was
      linked by various spacers to selected hydrophobic or polar motifs, which were
      designed to probe the protein surface surrounding the cationic heparan sulfate
      binding sites of the growth factors in order to improve affinity and selectivity.
      The affinities of the compounds for the growth factors were measured by surface
      plasmon resonance solution affinity assays. A lead compound was identified with
      micromolar binding affinity toward both FGF-1 and VEGF (K(d)=84 and 49 MUM,
      respectively) and good selectivity over FGF-2 (29- and 51-fold, respectively).

PMID- 22615184
TI  - Strapped-porphyrin-based molecular turnstiles.
AB  - The synthesis of a series of molecular turnstiles that contained both H-bond
      donor and -acceptor sites was achieved. Their structures were based on tetra-aryl
      X(2)Sn(IV) porphyrins (X=Cl or OH) as H-bond-acceptor sites that were equipped
      with a rotor that contained a pyridyldiamide moiety as a H-bond donor. In the
      solution phase, 1D and 2D NMR spectroscopic analysis showed that switching
      between the closed state, which resulted from the formation of intramolecular H
      bonds, and the open state of the turnstile was achieved by using external H-bond
      acceptor molecules, such as DMSO. The solid-state structure of the closed state
      of the turnstile was established by single-crystal X-ray diffraction.

PMID- 22615182
TI  - Augmenting the articular cartilage-implant interface: Functionalizing with a
      collagen adhesion protein.
AB  - The lack of integration between implants and articular cartilage is an unsolved
      problem that negatively impacts the development of treatments for focal cartilage
      defects. Many approaches attempt to increase the number of matrix-producing cells
      that can migrate to the interface, which may help to reinforce the boundary over
      time but does not address the problems associated with an initially unstable
      interface. The objective of this study was to develop a bioadhesive implant to
      create an immediate bond with the extracellular matrix components of articular
      cartilage. We hypothesized that implant-bound collagen adhesion protein (CNA)
      would increase the interfacial strength between a poly(vinly alcohol) implant and
      an articular cartilage immediately after implantation, without preventing cell
      migration into the implant. By way of a series of in vitro immunohistochemical
      and mechanical experiments, we demonstrated that (i) free CNA can bind to
      articular cartilage, (ii) implant-bound CNA can bind to collagen type II and
      (iii) implants functionalized with CNA result in a fourfold increase in
      interfacial strength with cartilage relative to untreated implants at day zero.
      Of note, the interfacial strength significantly decreased after 21 days in
      culture, which may be an indication that the protein itself has lost its
      effectiveness. Our data suggest that functionalizing scaffolds with CNA may be a
      viable approach toward creating an initially stable interface between scaffolds
      and articular cartilage. Further efforts are required to ensure long-term
      interface stability.

PMID- 22615185
TI  - A comparison of different bedside techniques to determine endotracheal tube
      position in a neonatal piglet model.
AB  - RATIONALE: Endotracheal tube (ETT) malposition is common and an increasing number
      of non-invasive techniques to aid rapid identification of tube position are
      available. Electrical impedance tomography (EIT) is advocated as a tool to
      monitor ventilation. OBJECTIVE: This study aimed to compare EIT with five other
      non-invasive techniques for identifying ETT position in a piglet model.
      METHODOLOGY: Six saline lavage surfactant-depleted piglets were studied. Periods
      of ventilation with ETT placed in the oesophagus or a main bronchus (MB) were
      compared with an appropriately placed mid-tracheal ETT. Colorimetric end-tidal
      CO(2) (Pedi-Cap(r)), SpO(2) and heart rate, tidal volume (${?rm V}_{{?rm T}_{{?rm
      ao}} } $) using a hot-wire anemometer at the airway opening, tidal volume using
      respiratory inductive plethysmography (${?rm V}_{{?rm T}_{{?rm RIP}} } $) and
      regional tidal ventilation within each hemithorax (EIT) were measured. RESULTS:
      Oesophageal ventilation: Pedi-Cap(r) demonstrated absence of color change. ${?rm
      V}_{{?rm T}_{{?rm ao}} } $, ${?rm V}_{{?rm T}_{{?rm RIP}} } $, and EIT correctly
      demonstrated no tidal ventilation. SpO(2) decreased from mean (SD) 96 (2)% to 74
      (12)% (P < 0.05; Bonferroni post-test), without heart rate change. MB
      ventilation: SpO(2) , heart rate and Pedi-Cap(r) were unchanged compared with mid
      tracheal position. ${?rm V}_{{?rm T}_{{?rm ao}} } $ and ${?rm V}_{{?rm T}_{{?rm
      RIP}} } $ decreased from a mean (SD) 10.8 (5.6) ml/kg and 14.6 (6.2) ml/kg to 5.5
      (1.9) ml/kg and 6.4 (2.6) ml/kg (both P < 0.05; Bonferroni post-test). EIT
      identified the side of MB ventilation, with a mean (SD) 95 (3)% reduction in
      tidal volume in the unventilated lung. CONCLUSIONS: EIT not only correctly
      identified oesophageal ventilation but also localized the side of MB ventilation.
      At present, no one technique is without limitations and clinicians should utilize
      a combination in addition to clinical judgement.

PMID- 22615186
TI  - Microglial activatory (immunoreceptor tyrosine-based activation motif)- and
      inhibitory (immunoreceptor tyrosine-based inhibition motif)-signaling receptors
      for recognition of the neuronal glycocalyx.
AB  - Microglia sense intact or lesioned cells of the central nervous system (CNS) and
      respond accordingly. To fulfill this task, microglia express a whole set of
      recognition receptors. Fc receptors and DAP12 (TYROBP)-associated receptors such
      as microglial triggering receptor expressed on myeloid cells-2 (TREM2) and the
      complement receptor-3 (CR3, CD11b/CD18) trigger the immunoreceptor tyrosine-based
      activation motif (ITAM)-signaling cascade, resulting in microglial activation,
      migration, and phagocytosis. Those receptors are counter-regulated by
      immunoreceptor tyrosine-based inhibition motif (ITIM)-signaling receptors, such
      as sialic acid-binding immunoglobulin superfamily lectins (Siglecs). Siglecs
      recognize the sialic acid cap of healthy neurons thus leading to an ITIM
      signaling that turns down microglial immune responses and phagocytosis. In
      contrast, desialylated neuronal processes are phagocytosed by microglial CR3
      signaling via an adaptor protein containing an ITAM. Thus, the aberrant terminal
      glycosylation of neuronal surface glycoproteins and glycolipids could serve as a
      flag for microglia, which display a multitude of diverse carbohydrate-binding
      receptors that monitor the neuronal physical condition and respond via their ITIM
      or ITAM-signaling cascade accordingly.

PMID- 22615187
TI  - Structural characteristics of graphane-type C and BN nanostructures by periodic
      local MP2 approach.
AB  - The structural characteristics of fully-hydrogenated carbon and boron nitride
      mono- and multilayer slabs, together with nanotubes derived from the slabs, are
      investigated mainly by means of periodic local second-order Moller-Plesset
      perturbation (LMP2) calculations and the results are compared with Hartree-Fock
      (HF), density functional theory (DFT), and dispersion function-augmented DFT (DFT
      D) obtained ones. The investigated systems are structurally analogous to (111)
      and (110) slabs of diamond, where the hydrogenated (111) slab of diamond
      corresponds to the experimentally known graphane. Multilayering of monolayers and
      nanotubes is energetically favorable at the LMP2 level for both C and BN, while
      HF and DFT are not able to reproduce this behavior for CH systems. The work
      highlights the importance of utilizing methods capable of properly describing
      weak interactions in the investigation of dispersively-bound systems such as the
      multilayered graphanes and the corresponding nanotubes.

PMID- 22615188
TI  - Direct electrophilic N-trifluoromethylation of azoles by a hypervalent iodine
      reagent.
AB  - Effective CF(3)  transfer: Various electron-rich nitrogen heterocycles
      (pyrazoles, triazoles, and tetrazoles) can be directly N-trifluoromethylated by a
      hypervalent iodine reagent in an efficient manner. The optimized procedure, which
      includes an in situ silylation of the substrate followed by an acid-catalyzed
      CF(3)  transfer, provides ready access to a series of new and previously
      challenging or inaccessible NCF(3)  compounds.

PMID- 22615189
TI  - Compositional dependence of hematopoietic stem cells expansion on bioceramic
      composite scaffolds for bone tissue engineering.
AB  - Bioceramics are although well known for their osteoinductive and osseointegrative
      properties in bone tissue regeneration, yet, they are inappropriate for load
      bearing applications due to inadequate mechanical strength. In this article, the
      authors report the expansion of hematopoietic stem cells (HSCs) on as-synthesized
      composite scaffolds from hydroxyapatite and beta-tricalcium phosphate for bone
      tissue engineering, in an adequate load-bearing application. The physical,
      structural, and mechanical properties of the composite scaffolds have been
      examined and correlated with the in vitro adhesion pattern of HSCs. The results
      indicated that the response of HSCs varies with change in the stoichiometry of
      composite scaffolds. The H2T2 scaffolds have exhibited the highest expansion of
      CD34+ cells and long-term culture initiating cells when compared with other
      stoichiometries. The results suggest that H2T2 composite can be a potential
      strategic bone-graft substitute in contrast with monolithic bioceramics, serving
      a dual role of bioresorbability and enhanced load-bearing capacity.

PMID- 22615190
TI  - L-Carnitine plus cilostazol versus cilostazol alone for the treatment of
      claudication in patients with peripheral artery disease: a multicenter,
      randomized, double-blind, placebo-controlled trial.
AB  - Intermittent claudication (IC) is the predominant symptom of peripheral artery
      disease (PAD), and is associated with reduced exercise capacity. The
      pathophysiology of IC is related to reduced blood flow and impaired skeletal
      muscle oxidative metabolism; however, the efficacy of metabolic therapies is not
      well established. We evaluated the effect of cilostazol plus l-carnitine versus
      cilostazol alone on exercise performance, quality of life (QOL), and safety. In a
      double-blind, placebo-controlled trial, PAD patients with stable IC were
      randomized to either l-carnitine 1 g or matching placebo twice-daily, on a
      background of cilostazol. Treadmill and QOL assessments were performed at
      baseline, 90, and 180 days. The primary endpoint was the difference between
      groups in the natural-log-transformed (ln) ratio in peak walking time (PWT)
      between baseline and 180 days. The combination of cilostazol and l-carnitine was
      well tolerated. In the modified intent-to-treat population (n = 145), the mean ln
      ratio in PWT was 0.241 for cilostazol/l-carnitine versus 0.134 for
      cilostazol/placebo (p = 0.076), corresponding to mean increases of 1.99 and 1.36
      minutes, respectively. In the per-protocol population (n = 120), the mean ln
      ratio in PWT was 0.267 for cilostazol/l-carnitine versus 0.145 for
      cilostazol/placebo (p = 0.048). QOL measures were also improved in the
      cilostazol/l-carnitine group. These findings support larger trials of l-carnitine
      in combination with cilostazol in the treatment of IC.

PMID- 22615191
TI  - Red cell distribution width and risk of peripheral artery disease: analysis of
      National Health and Nutrition Examination Survey 1999-2004.
AB  - Red cell distribution width (RDW) is an independent predictor of the 10-year
      estimated risk of coronary heart disease (CHD) events. However, RDW's association
      with peripheral artery disease (PAD) - a CHD risk equivalent - has not been
      evaluated to date. In this cross-sectional study, we examined 6950 participants
      of the National Health and Nutrition Examination Survey, 1999-2004. PAD was
      defined as an ankle-brachial index below 0.9 (n = 618). RDW was divided into
      quartiles (Q) (Q1: <= 12.2; Q2: 12.3-12.5; Q3: 12.6-13.0; Q4: >= 13.1) and PAD
      risk was compared across these quartiles using adjusted multivariate logistic
      regression. A graded increase in prevalent PAD with increasing RDW quartiles was
      observed (4.2% in Q1 vs 13.9% in Q4; test of trend p < 0.001). Risk of PAD was
      significantly higher (odds ratio (OR) 1.19, 95% confidence interval (CI): 1.06
      1.34; p = 0.003) after adjusting for age, sex, race, body mass index,
      hypertension, hyperlipidemia, diabetes, smoking, estimated glomerular filtration
      rate, C-reactive protein, hemoglobin, mean corpuscular volume, and nutritional
      factors (folate, iron and vitamin B(12)) deficiencies with each unit (0.1)
      increase in RDW. Upon receiver-operating characteristics analysis, the predictive
      accuracy of the American College of Cardiology / American Heart Association
      (ACC/AHA)-defined PAD screening criteria (for a high-risk population) was 0.657
      at best, but improved significantly (0.727) after addition of RDW (p < 0.0001).
      In conclusion, higher levels of RDW are independently associated with a higher
      risk of PAD and can significantly improve the risk prediction beyond that
      estimated by ACC/AHA-defined PAD screening criteria.

PMID- 22615192
TI  - 6-halogenochromones bearing tryptamine: one-step access to potent and highly
      selective inhibitors of breast cancer resistance protein.

PMID- 22615193
TI  - Detection and reactivity of a palladium alkoxycarbene.
AB  - A characterful carbene: The high electrophilicity of a genuine palladium
      alkoxycarbene, obtained by transmetalation, is evident in its reactivity.
      Nucleophilic attack on two electrophilic centers (red) is observed. Alkyl
      abstraction and addition to the carbene carbon by different nucleophiles occur.
      This palladium(II) alkoxycarbene also undergoes comproportionation with
      palladium(0) to give an unprecedented palladium(I) dimeric carbene (see scheme).

PMID- 22615195
TI  - The nature of chemical bonds from PNOF5 calculations.
AB  - Natural orbital functional theory (NOFT) is used for the first time in the
      analysis of different types of chemical bonds. Concretely, the Piris natural
      orbital functional PNOF5 is used. It provides a localization scheme that yields
      an orbital picture which agrees very well with the empirical valence shell
      electron pair repulsion theory (VSEPR) and Bent's rule, as well as with other
      theoretical pictures provided by valence bond (VB) or linear combination of
      atomic orbitals-molecular orbital (LCAO-MO) methods. In this context, PNOF5
      provides a novel tool for chemical bond analysis. In this work, PNOF5 is applied
      to selected molecules that have ionic, polar covalent, covalent, multiple (sigma
      and pi), 3c-2e, and 3c-4e bonds.

PMID- 22615194
TI  - Optimism predicts resilience in repatriated prisoners of war: a 37-year
      longitudinal study.
AB  - Resilience, exhibiting intact psychological functioning despite exposure to
      trauma, is one perspective as to why some people who are exposed to trauma do not
      develop symptoms. This study examines the prisoner of war experience to expand
      our understanding of this phenomenon in extreme cases of trauma such as prolonged
      captivity, malnourishment, and physical and psychological torture. The study
      examined the United States' longest detained American prisoners of war, those
      held in Vietnam in the 1960s through early 1970s. A logistic regression analysis
      using resilience, defined as never receiving any psychiatric diagnosis over a 37
      year follow-up period, as the outcome was performed (n = 224 with complete data).
      Six variables showing at least small effects emerged: officer/enlisted status,
      age at time of capture, length of solitary confinement, low
      antisocial/psychopathic personality traits, low posttraumatic stress symptoms
      following repatriation, and optimism. Odds ratios (ORs) and confidence intervals
      (CIs) confirmed the significance and relative strength of these variables, with a
      range from OR = 0.54, 95% CI [0.13, 2.29] to OR = 1.11, 95% CI [1.04, 1.17]. When
      all variables were examined continuously and categorically, dispositional
      optimism was the strongest variable, accounting for 17%, continuously, and 14%,
      categorically. We discuss optimism as a protective factor for confronting trauma
      and the possibility of training to increase it.

PMID- 22615196
TI  - 1H-phosphindoles as structural units in the synthesis of chiral helicenes.

PMID- 22615197
TI  - Adhesion of MC3T3-E1 cells bound to dentin phosphoprotein specifically bound to
      collagen type I.
AB  - Dentin sialophosphoprotein (DSPP) is a member of the SIBLING (small integrin
      binding N-linked glycoprotein) family of proteins commonly found in mineralized
      tissues. Dentin phosphoprotein (DPP) is a naturally occurring subdomain of DSPP
      that contains the cell binding RGD sequence. Previously, the orientation and
      conformation of other SIBLING family members specifically bound to collagen I
      have been investigated with respect to their cell adhesion properties. In this
      study, the orientation of DPP under similar circumstances is examined, and the
      results are discussed relative to the previous investigations. Radiolabeled
      adsorption isotherms were developed for DPP adsorbing to both tissue culture
      polystyrene (TCPS) and collagen coated TCPS. Then, a MC3T3-E1 cell adhesion assay
      was performed on TCPS and collagen coated TCPS in the presence of identical
      amounts of adsorbed DPP. It was discovered that there was a significant
      difference in the number of bound cells on the TCPS and collagen coated TCPS,
      with a preference for TCPS. Furthermore, a cell inhibition assay was conducted to
      confirm that the cell binding that occurred was due to specific integrin
      interactions with the RGD sequence of DPP. These results suggest that the
      orientation of DPP, rather than its conformation, dictates the accessibility of
      the cell binding RGD domains of DPP and that the RGD sequence in DPP is less
      accessible when DPP is specifically bound to collagen. The results obtained in
      this study are in stark contrast to previous studies with related SIBLING
      proteins, and suggest that DPP does not play a key role in cell binding to the
      collagen matrix of developing bone.

PMID- 22615198
TI  - Synthesis, structure-activity relationship and docking studies of substituted
      aryl thiazolyl phenylsulfonamides as potential protein tyrosine phosphatase 1B
      inhibitors.

PMID- 22615199
TI  - Mg-catalyzed enantioselective benzylic C-H bond functionalization of
      isoindolinones: addition to imines.
AB  - Access to chiral isoindolinones: The Mg-catalyzed enantioselective benzylic C-H
      bond functionalization of isoindolinones is described. A Bu(2) Mg/Schiff base
      catalyst (1:1) promoted the enantioselective addition of N-Boc-isoindolinones to
      aryl, heteroaryl, alkenyl, and alkyl imines, giving 3-substituted isoindolinones
      in 84-99 % ee and 50:50-91:9 d.r. (see scheme).

PMID- 22615200
TI  - Ambulatory blood pressure monitoring in Chinese children with obstructive sleep
      apnea/hypopnea syndrome.
AB  - OBJECTIVE: Obstructive sleep apnea/hypopnea syndrome (OSAHS) is a common sleep
      problem. The aim of this study is to investigate the association between OSAHS
      and blood pressure (BP) in snoring children. METHODS: Snoring children were
      recruited from January 2009 to December 2010. Clinical history was taken
      accompanied by a physical examination and polysomnography were performed. A child
      with an apnea/hypopnea index (AHI) greater than 5 hr(-1) or obstructive apnea
      index (OAI) greater than 1 hr(-1) was diagnosed as having OSAHS. Ambulatory BP
      monitoring was performed for each child. BP load, BP index and nocturnal BP
      dipping were calculated for each child. RESULTS: One hundred forty-five children
      with snoring were recruited and 107 of them were diagnosed with OSAHS. There were
      no differences between those with or without OSA in age or gender distribution.
      The OSAHS children had higher mean nighttime systolic and diastolic BP, increased
      BP load, and decreased nocturnal BP dipping compared to the non-OSAHS children
      (SBP: P = 0.03, DBP: P < 0.001, BP load: P = 0.001, SBP dipping: P = 0.03, DBP
      dipping: P = 0.04). Multiple regression analysis showed that mean nighttime
      systolic BP was related to age, obesity, and oxygen desaturation index (ODI) (P =
      0.04, 0.03, and 0.02 respectively), while mean nighttime diastolic BP was related
      to obesity and ODI (P = 0.03 and 0.04, respectively). CONCLUSIONS: OSAHS children
      had a higher nocturnal BP than non-OSAHS children and dysregulation of BP control
      reflected by decreased nocturnal BP dipping. Frequency of oxygen desaturation,
      apneas, and obesity were related to BP.

PMID- 22615201
TI  - Solid waste management in Croatia in response to the European Landfill Directive.
AB  - The European Landfill Directive 99/31/EC represents the most influential piece of
      waste legislation on the management of municipal solid waste. In addition to
      technical standards regarding the design and location of landfills, it calls for
      a decrease in the amount of biodegradable waste landfilled. In order to meet the
      reduction targets set in the Landfill Directive, national solid waste strategies
      need to be changed. This article outlines the impact of the Landfill Directive on
      the Croatian waste management strategy and discusses the key challenges of its
      implementation. In addition, three scenarios of future waste management
      (mechanical biological pre-treatment, waste-to-energy and landfilling) have been
      investigated and evaluated regarding environmental impacts and affordability. The
      results of the analysis show that Croatia has transposed the said Directive into
      its own legislation in an exemplary way. The developed national waste management
      strategy foresees the set up of a separate collection of recyclables, waste pre
      treatment of MSW, as well as the upgrading of existing disposal sites to sanitary
      landfills. However, the practical progress of carrying out provisions implemented
      on paper is lagging behind. Concerning the investigated scenarios the results of
      the evaluation indicate that mechanical biological pre-treatment in conjunction
      with separate collection of recyclables appears to be the most feasible option
      (in terms of economic and ecologic parameters). This result is in line with the
      proposed national waste management strategy.

PMID- 22615202
TI  - "Nothing really matters": emotional numbing as a link between trauma exposure and
      callousness in delinquent youth.
AB  - This study investigated the interrelations among trauma exposure, emotional
      numbing, and callous-unemotional traits in a sample of 276 youth (68 girls and
      208 boys) recruited from 2 juvenile detention centers. Youth completed interview
      measures of trauma exposure and betrayal trauma, as well as self-report measures
      of emotional numbing and callous-unemotional traits. Results of path analyses
      using nonparametric bootstrapping procedures indicated findings consistent with
      the hypothesis that the association between trauma exposure and callous
      unemotional traits was mediated by the general numbing of emotions, R(2)  = .40,
      and also specifically by numbing of sadness, R(2)  = .27. In addition, further
      analyses indicated that numbing of fear, R(2)  = .18, and sadness, R(2)  = .26,
      statistically mediated the relations to callous-unemotional traits only for those
      traumatic experiences involving betrayal. Gender was not found to moderate these
      effects.

PMID- 22615203
TI  - Loss of TNF signaling facilitates the development of a novel Ly-6C(low)
      macrophage population permissive for Leishmania major infection.
AB  - In the absence of TNF, the normally resistant C57BL/6 (B6.WT) strain develops a
      fatal, progressive form of leishmaniasis after infection with Leishmania major.
      It is not yet understood which TNF activity or the lack thereof is responsible
      for the dramatic progression of leishmaniasis in TNF-negative (B6.TNF(-/-)) mice.
      To elucidate the underlying mechanisms resulting in the fatal outcome of L. major
      infection in this gene-deficient mouse strain, we analyzed the monocytic
      component of the inflammatory infiltrate in the draining popliteal lymph node and
      the site of the infection using multicolor flow cytometry. The leukocytic
      infiltrate within the draining lymph node and footpad of B6.TNF(-/-) mice
      resembled that of B6.WT mice over the first 2 wk of cutaneous L. major infection.
      Thereafter, the B6.TNF(-/-) mice showed an increase of CD11c(+)Ly-6C(+)CCR2(+)
      monocytic dendritic cells within the popliteal lymph node in comparison with
      B6.WT mice. This increase of inflammatory dendritic cells was paired with the
      accumulation of a novel CD11b(+)Ly-6C(low)CCR2(low) population that was not
      present in B6.WT mice. This B6.TNF(-/-)- and B6.TNFR1(-/-)-specific cell
      population was CD115(+)Ly-6G(-)iNOS(-), not apoptotic, and harbored large numbers
      of parasites.

PMID- 22615205
TI  - Dendritic cell-specific transcript: dendritic cell marker and regulator of TLR
      induced cytokine production.
AB  - Dendritic cells (DCs) are the professional APCs of the immune system that dictate
      the type and course of an immune response. Molecular understanding of DC biology
      is important for the design of DC-based immunotherapies and optimal clinical
      applications in vaccination settings. Previously, we isolated and characterized
      the cDNA-encoding dendritic cell-specific transcript (DC-SCRIPT; also known as
      ZNF366). DC-SCRIPT mRNA expression in the immune system was confined to DCs and
      was reported to be an early hallmark of DC differentiation. In this study, we
      demonstrate IL-4 to be the dominant factor for DC-SCRIPT expression in human
      monocyte-derived DCs. In addition, to our knowledge, we show for the first time
      endogenous DC-SCRIPT protein expression in human DCs both in vitro and in situ.
      DC-SCRIPT protein is detected early upon differentiation of monocytes into DCs
      and is also present in multiple freshly isolated DC subsets. Maturation of DCs
      with TLR ligands further increased DC-SCRIPT mRNA expression, suggesting a role
      in DC maturation. Indeed, small interfering RNA-mediated knockdown of DC-SCRIPT
      affected the cytokine response upon TLR stimulation. These DCs displayed enhanced
      IL-10 and decreased IL-12 production, compared with wild-type DCs. Silencing of
      IL-10 in DC-SCRIPT knockdown DCs rescued IL-12 expression, suggesting a primary
      role for DC-SCRIPT in the regulation of IL-10 production.

PMID- 22615204
TI  - Human CCR4+ CCR6+ Th17 cells suppress autologous CD8+ T cell responses.
AB  - The role of Th17 cells in cancer patients remains unclear and controversial. In
      this study, we have analyzed the phenotype of in vitro primed Th17 cells and
      further characterized their function on the basis of CCR4 and CCR6 expression. We
      show a novel function for a subset of IL-17-secreting CD4(+) T cells, namely,
      CCR4(+)CCR6(+)Th17 cells. When cultured together, CCR4(+)CCR6(+)Th17 cells
      suppressed the lytic function, proliferation, and cytokine secretion of both Ag
      specific and CD3/CD28/CD2-stimulated autologous CD8(+) T cells. In contrast,
      CCR4(-)CCR6(+) CD4(+) T cells, which also secrete IL-17, did not affect the
      CD8(+) T cells. Suppression of CD8(+) T cells by CCR4(+)CCR6(+)Th17 cells was
      partially dependent on TGF-beta, because neutralization of TGF-beta in cocultures
      reversed their suppressor function. In addition, we also found an increase in the
      frequency of CCR4(+)CCR6(+), but not CCR4(-)CCR6(+) Th17 cells in peripheral
      blood of hepatocellular carcinoma patients. Our study not only underlies the
      importance of analysis of subsets within Th17 cells to understand their function,
      but also suggests Th17 cells as yet another immune evasion mechanism in
      hepatocellular carcinoma. This has important implications when studying the
      mechanisms of carcinogenesis, as well as designing effective immunotherapy
      protocols for patients with cancer.

PMID- 22615207
TI  - Dimerization of NKp46 receptor is essential for NKp46-mediated lysis:
      characterization of the dimerization site by epitope mapping.
AB  - NKp46 is a primary activating receptor of NK cells that is involved in lysis of
      target cells by NK cells. Previous studies showed that the membrane-proximal
      domain of NKp46 (NKp46D2) retained the binding of NKp46 to its ligands and is
      involved in lysis. We studied NKp46D2 by using a peptide-based epitope mapping
      approach and identified an NKp46D2-derived linear epitope that inhibited NKp46
      mediated lysis. The epitope, designated as pep4 (aa 136-155), interacted with
      NKp46, and lysis by NK cells was inhibited by the presence of pep4. Through
      modeling and mutagenesis, we showed that pep4 could be involved in NKp46
      homodimerization. R145 and D147 contribute to the function of pep4, and R145Q
      mutation in recombinant NKp46 reduced its binding to target cells. At the
      cellular level, fluorescent resonance energy transfer analysis revealed that pep4
      is indeed involved in dimerization of cell membrane-associated NKp46. We suggest
      that the NKp46-derived pep4 site is part of the dimerization surface of NKp46 and
      that NKp46 dimerization contributes to NKp46-mediated lysis by NK cells.

PMID- 22615206
TI  - Glucocorticoids relieve collectin-driven suppression of apoptotic cell uptake in
      murine alveolar macrophages through downregulation of SIRPalpha.
AB  - The lung environment actively inhibits apoptotic cell (AC) uptake by alveolar
      macrophages (AMos) via lung collectin signaling through signal regulatory protein
      alpha (SIRPalpha). Even brief glucocorticoid (GC) treatment during maturation of
      human blood monocyte-derived or murine bone marrow-derived macrophages (Mos)
      increases their AC uptake. Whether GCs similarly impact differentiated tissue Mos
      and the mechanisms for this rapid response are unknown and important to define,
      given the widespread therapeutic use of inhaled GCs. We found that the GC
      fluticasone rapidly and dose-dependently increased AC uptake by murine AMos
      without a requirement for protein synthesis. Fluticasone rapidly suppressed AMo
      expression of SIRPalpha mRNA and surface protein, and also activated a more
      delayed, translation-dependent upregulation of AC recognition receptors that was
      not required for the early increase in AC uptake. Consistent with a role for
      SIRPalpha suppression in rapid GC action, murine peritoneal Mos that had not been
      exposed to lung collectins showed delayed, but not rapid, increase in AC uptake.
      However, pretreatment of peritoneal Mos with the lung collectin surfactant
      protein D inhibited AC uptake, and fluticasone treatment rapidly reversed this
      inhibition. Thus, GCs act not only by upregulating AC recognition receptors
      during Mo maturation but also via a novel rapid downregulation of SIRPalpha
      expression by differentiated tissue Mos. Release of AMos from inhibition of AC
      uptake by lung collectins may, in part, explain the beneficial role of inhaled
      GCs in inflammatory lung diseases, especially emphysema, in which there is both
      increased lung parenchymal cell apoptosis and defective AC uptake by AMos.

PMID- 22615209
TI  - Spiral intramolecular charge transfer and large first hyperpolarizability in
      Mobius cyclacenes: new insight into the localized pi electrons.
AB  - Much effort has been devoted to investigating the unusual properties of the pi
      electrons in Mobius cyclacenes, which are localized in a special region. However,
      the localized pi electrons are a disadvantage for applications in
      optoelectronics, because intramolecular charge transfer is limited. This raises
      the question of how the intramolecular charge transfer of a Mobius cyclacene with
      clearly localized pi electrons can be enhanced. To this end, [8]Mobius cyclacene
      ([8]MC) is used as a conjugated bridge in a donor-pi-conjugated bridge-acceptor
      (D-pi-A) system, and NH(2)-6-[8]MC-10-NO(2) exhibits a fascinating spiral charge
      transfer transition character that results in a significant difference in dipole
      moments DeltaMU between the ground state and the crucial excited state. The
      DeltaMU value of 6.832 D for NH(2)-6-[8]MC-10-NO(2) is clearly larger than that
      of 0.209 D for [8]MC. Correspondingly, the first hyperpolarizability of NH(2)-6
      [8]MC-10-NO(2) of 12,467 a.u. is dramatically larger than that of 261 a.u. for
      [8]MC. Thus, constructing a D-pi-A framework is an effective strategy to induce
      greater spiral intramolecular charge transfer in MC although the pi electrons are
      localized in a special region. This new insight into the properties of pi
      electrons in Mobius cyclacenes may provide valuable information for their
      applications in optoelectronics.

PMID- 22615208
TI  - Adjuvant-like effect of vaccinia virus 14K protein: a case study with malaria
      vaccine based on the circumsporozoite protein.
AB  - Development of subunit vaccines for malaria that elicit a strong, long-term
      memory response is an intensive area of research, with the focus on improving the
      immunogenicity of a circumsporozoite (CS) protein-based vaccine. In this study,
      we found that a chimeric protein, formed by fusing vaccinia virus protein 14K
      (A27) to the CS of Plasmodium yoelii, induces strong effector memory CD8(+) T
      cell responses in addition to high-affinity Abs when used as a priming agent in
      the absence of any adjuvant, followed by an attenuated vaccinia virus boost
      expressing CS in murine models. Moreover, priming with the chimeric protein
      improved the magnitude and polyfunctionality of cytokine-secreting CD8(+) T
      cells. This fusion protein formed oligomers/aggregates that led to activation of
      STAT-1 and IFN regulatory factor-3 in human macrophages, indicating a type I IFN
      response, resulting in NO, IL-12, and IL-6 induction. Furthermore, this
      vaccination regimen inhibited the liver stage development of the parasite,
      resulting in sterile protection. In summary, we propose a novel approach in
      designing CS based pre-erythrocytic vaccines against Plasmodium using the
      adjuvant-like effect of the immunogenic vaccinia virus protein 14K.

PMID- 22615211
TI  - Interfacial self-assembly of water-soluble cationic porphyrins for the reduction
      of oxygen to water.
AB  - Meet at the border: Assembly of the water-soluble cobalt tetrakis(N
      methylpyridinium-4-yl)porphyrin [CoTMPyP](4+) at soft interfaces is enhanced and
      stabilized by its interfacial interaction with the lipophilic anion
      (C(6)F(5))(4)B(-). The supramolecular structure thus formed provides excellent
      catalytic activity in the four-electron reduction of oxygen.

PMID- 22615210
TI  - Tissue engineering of ureteral grafts by seeding urothelial differentiated hADSCs
      onto biodegradable ureteral scaffolds.
AB  - The study is aimed to evaluate the differentiation potential of human adipose
      derived stem cells (hADSCs) into urothelial lineage, and to assess possibility of
      constructing ureteral grafts using the differentiated hADSCs and a novel
      polylactic acid (PLA)/collagen scaffolds. HADSCs were indirectly cocultured with
      urothelial cells in a transwell coculture system for urothelial differentiation.
      After 14 days coculturing, differentiation was evaluated by detecting urothelial
      lineage markers (cytokeratin-18 and uroplakin 2) in mRNA and protein level. Then
      the differentiated hADSCs were seeded onto PLA/collagen ureteral scaffolds and
      cultured in vitro for 1 week. The biocompatibility of the scaffolds was tested by
      scanning electron microscopy (SEM) and MTT analysis. At last, the cell/scafflod
      grafts were subcutaneously implanted into 4-week-old female athymic mice for 14
      days. The results demonstrated that the hADSCs could be efficiently induced into
      urothelial lineage by indirect coculture. The differentiated cells seeded onto
      the PLA/collagen ureteral scaffolds survived up to 7 days and maintained
      proliferation in vitro, which indicated that the scaffolds displayed good
      biocompatibility. In vivo study showed that the differentiated cells in the
      grafts survived, formed multiple layers on the scaffolds and expressed urothelial
      lineage markers. In conclusion, hADSCs may serve as an alternative cell resource
      in cell-based tissue engineering for ureteral reconstruction. These cells could
      be employed to construct a model of ureteral engineering grafts and be
      effectively applied in vivo, which could be a new strategy on ureteral
      replacement with applicable potential in clinical research.

PMID- 22615212
TI  - Organic-inorganic hybrids based on ultrathin oxide layers: designed
      nanostructures for molecular recognition.
AB  - The application of layered solids for molecular recognition is summarized. By
      using layered solids (silicates, aluminosilicates, titanates, hydroxides, and so
      on), ions and molecules can be concentrated from aqueous and vapor phases. The
      large surface area and tunable surface properties derived from the layered
      structures contribute to molecular recognition. The choice of materials and
      modification of the nanostructure were carefully investigated to optimize the
      performance based on molecular recognition (selective adsorption, substrate
      selective reaction, detection, etc.). The progress made in materials syntheses
      (variation of layered materials, sophisticated modification, controlled
      morphology, and processing) has made the design of materials more attractive and
      realistic.

PMID- 22615213
TI  - Controlling the size and morphology of Au@Pd core-shell nanocrystals by
      manipulating the kinetics of seeded growth.
AB  - This article reports a systematic study of the seed-mediated growth of Au@Pd core
      shell nanocrystals with a variety of controlled sizes and morphologies. The key
      to the success of this synthesis is to manipulate the reaction kinetics by tuning
      a set of reaction parameters, including the type and concentration of capping
      agent, the amount of ascorbic acid used as the reducing agent, and the injection
      rate used for the precursor solution. Starting from Au nanospheres of 11 nm in
      diameter as the seeds, Au@Pd core-shell nanocrystals with a number of
      morphologies, including octahedra, concave octahedra, rectangular bars, cubes,
      concave cubes, and dendrites, could all be obtained by simply altering the
      reaction rate. For the first time, it was possible to generate Au@Pd nanocrystals
      with concave structures on the surfaces while their sizes were kept below 20 nm.
      In addition, the as-prepared Au@Pd nanocubes can be used as seeds to generate
      Au@Pd@Au and Au@Pd@Au@Pd nanocrystals with multishelled structures.

PMID- 22615214
TI  - Chiral chemical absorption property of a cross-linked poly(N-isopropyl acrylamide
      co-sodium acrylate) thermoresponsive smart gel.
AB  - This investigation leads to the chiral chemical absorption property of a
      thermoresponsive gel material. D-(+)-alpha-phenyl ethyl amine was taken as the
      chiral chemical. The gel material was synthesized by polymerizing 1:1 mole ratio
      of N-isopropyl acrylamide and Na-acrylate along with methylene bisacrylamide (2
      wt.% of total monomer) as a cross-linker using ammonium persulfate as an
      initiator and N, N, N', N'-tetra-methyl ethylene diamine as an accelerator. The
      microporous nature of the gel material is observed by scanning electron
      microscope as well as by surface analysis. It is a pH as well as thermoresponsive
      gel. The highest gel swelling is observed at around pH 8.2 at room temperature
      (30  degrees C). The gel contains carboxylate (-COO(-)) group in this slightly
      alkaline condition. In the ionic state, the mutual repulsion of the ionic groups
      helps in swelling the gel. The lower critical solution temperature (LCST) of the
      gel is observed to be about 38  degrees C, which is higher than that of poly N
      isopropyl acrylamide itself (32  degrees C). This corroborates with the theory
      and other reported results that LCST increases with the incorporation of ionic
      moiety in the cross-linked copolymer. The chiral chemical absorption of the gel
      material was monitored by measuring circular dichroism of the chiral compound in
      the presence and absence of gel using a circular dichroism spectropolarimeter (J
      810 L) (JASCO International Co., Ltd., Tokyo, Japan). About 18% of D-(+)-alpha
      phenyl ethyl amine is absorbed from its aqueous solution by 0.01 g of dry gel
      material (particle size: 106-212 um) at room temperature. The absorption of the
      chiral compound is reversible with temperature having a sudden jump at LCST (38 
      degrees C) of the gel material.

PMID- 22615215
TI  - Recent progress and challenges in graphene nanoribbon synthesis.
AB  - Graphene, the thinnest two-dimensional material in nature, has abundant
      distinctive properties, such as ultrahigh carrier mobility, superior thermal
      conductivity, very high surface-to-volume ratio, anomalous quantum Hall effect,
      and so on. Laterally confined, thin, and long strips of graphene, namely,
      graphene nanoribbons (GNRs), can open the bandgap in the semimetal and give it
      the potential to replace silicon in future electronics. Great efforts are devoted
      to achieving high-quality GNRs with narrow widths and smooth edges. This
      minireview reports the latest progress in experimental and theoretical studies on
      GNR synthesis. Different methods of GNR synthesis-unzipping of carbon nanotubes
      (CNTs), cutting of graphene, and the direct synthesis of GNRs-are discussed, and
      their advantages and disadvantages are compared in detail. Current challenges and
      the prospects in this rapidly developing field are also addressed.

PMID- 22615216
TI  - Titanium surfaces with nanotopography modulate cytokine production in cultured
      human gingival fibroblasts.
AB  - Implant topography is an important factor that influences many cell types. To
      understand the role of topography in the inflammatory events, we evaluated the
      response of human gingival fibroblasts (HGFs) by the release pattern of
      cytokines. HGFs were cultured on Ti discs for 24 and 48 h. Four different surface
      treatments were used: machining method (turned), blasting followed by an acid
      etching method (BAE), oxidative nanopatterning (ON) method, and an association of
      blasting followed by an acid-etching plus oxidative nanopatterning (BAE+ON)
      method. Extracellular levels of IL-6, IL-8, transforming growth factor beta (TGF
      beta), IL-4, and IL-10 were measured by enzyme-linked immunosorbant assay.
      Increased levels of IL-6 and IL-8 were observed in all surfaces after 24 h which
      decreased after 48 h. BAE, ON, and BAE+ON surfaces showed a reduction in IL-6
      levels compared with the turned after 48 h (p < 0.05). On one hand, IL-8
      production was lower in BAE+ON in comparison to the turned surface (p < 0.05). On
      the other hand, IL-4 showed increased levels with 48 h, which were significantly
      different between turned, BAE, and ON surfaces, but not with BAE+ON.
      Additionally, TGF-beta and IL-10 production were not detected. This study
      indicates that nanotopography might be important in the modulation of the
      inflammatory response in cultured HGFs.

PMID- 22615217
TI  - Shared decision-making in pediatric allogeneic blood and marrow transplantation:
      what if there is no decision to make?
AB  - INTRODUCTION: Shared decision-making between health care professionals, patients,
      parents, and guardians is widely recommended today. However, it is unclear what
      happens when collaborative language is used by physicians in clinical situations
      for which patients and parents/guardians believe there is no decision to be made.
      METHODS: We conducted a qualitative study of decision-making for pediatric
      allogeneic blood and marrow transplantation by interviewing patients, parents,
      grandparents, donor siblings, and nondonor children after the decision to proceed
      to transplant but before the transplantation. Each interview was audio recorded,
      transcribed, and coded for major themes. RESULTS: In total, 107 members of 30
      families at four sites were interviewed, including 15 patients, 22 mothers, 2
      stepmothers, 1 grandmother, 19 fathers, 3 stepfathers, 1 grandfather, 13 sibling
      donors, and 31 nondonor children (siblings, half-siblings, and cousins). In all,
      81% of parents/guardians, 73% of patients, 31% of donors, and 29% of other
      children reported there was no decision to be made. Almost all (88%)
      parents/guardians indicated that the physician's recommendation was a large
      determinant in their agreement to go forward with the transplantation. All
      parents/guardians reported that "agreeing to a plan" was a better description of
      what their consent entailed. CONCLUSIONS: To be respectful of patients and
      parents/guardians, we suggest that "agreeing to a plan" may be a better
      description for what parents/guardians must consider when the alternative to a
      transplantation is likely death. In this clinical context, the shared decision
      making model with a focus on "a decision to be made" may be misleading.

PMID- 22615218
TI  - Regio- and stereoselective monoamination of diketones without protecting groups.

PMID- 22615219
TI  - The fluorophore 4',6-diamidino-2-phenylindole (DAPI) induces DNA folding in long
      double-stranded DNA.
AB  - DAPI (4',6-diamidino-2-phenylindole) is a widely used fluorescent dye, whose
      complicated binding features to DNAs and RNAs have been the object of debates and
      are still not fully understood. In this study, different approaches were
      employed, including binding equilibrium measurements (spectrofluorometry),
      melting experiments (spectrophotometry), viscometric measurements, circular
      dichroism, and T-jump kinetic analyses; all data concur in shedding light on the
      complex mechanistic aspects of the binding mode of DAPI to natural DNA.
      Conditions are found that induce the mode of the DAPI/DNA interaction to change
      from groove binding to intercalation. Moreover, it is observed, for the first
      time, that DAPI is able to induce the formation of a rather compact polymer-dye
      adduct under particular conditions. The results suggest that this form is a
      folded or coiled DNA structure stabilized by DAPI dye bridges.

PMID- 22615220
TI  - Deoxygenative olefination reaction as the key step in the syntheses of deoxy and
      iminosugars.
AB  - Just a spoonful of sugar! A new synthetic strategy involving the use of a
      deoxygenative olefination reaction as the key step was developed for the
      preparation of deoxy and iminosugars in their optically active form (see scheme).
      This strategy has been proven successful by the use of a pentose, hexose,
      heptose, and disaccharide as the starting materials. Furthermore, it was applied
      in a formal total synthesis of iminosugar (-)-1-deoxy-L-fuconojirimycin, which
      can inhibit alpha-L-fucosidase.

PMID- 22615221
TI  - Liquid chromatographic separation of darunavir enantiomers on coated and
      immobilized amylose tris(3, 5-dimethylphenylcarbamate) chiral stationary phases.
AB  - Liquid chromatographic separation of darunavir enantiomers on covalently bonded
      and physically adsorbed polysaccharide chiral stationary phases was studied at
      different temperatures. The separations were accomplished under normal-phase
      conditions by using different combinations of hexane, organic modifiers (2
      propanol, 1-propanol and ethanol), and diethylamine as mobile phase solvents. The
      effect of organic modifiers and the column temperature on retention, separation,
      and resolution was investigated. The observed differences were explained in terms
      of the coated and immobilized nature of the two columns. Van't Hoff plots (ln k'
      vs. 1/T, ln alpha vs. 1/T) and apparent thermodynamic parameters were derived to
      understand the effect of temperature on separation.

PMID- 22615222
TI  - The supply of postdocs.

PMID- 22615223
TI  - Peer review in class: metrics and variations in a senior course.
AB  - Peer reviews are the generally accepted mode of quality assessment in scholarly
      communities; however, they are rarely used for evaluation at college levels. Over
      a period of 5 years, we have performed a peer review simulation at a senior level
      course in molecular genetics at the University of Guelph and have accumulated 393
      student peer reviews. We have used these to generate a summary of the metrics of
      this exercise. Our calculations show that student peer marks are highly variable
      and not suitable for numerical performance evaluation at the university level. On
      the other hand, student peer reviews can clearly recognize substandard
      performance. Hence, peer reviews can be used for the assessment of "pass/fail"
      type of assignments. Interestingly, student peers struggle to distinguish between
      good and excellent performance. These finding provide provocative insight on the
      process of peer review in general. We comment on the implications of this in
      class simulation for research communities and on potential pitfalls of peer
      reviews.

PMID- 22615224
TI  - Formulation of multiple choice questions as a revision exercise at the end of a
      teaching module in biochemistry.
AB  - The graduate medical students often get less opportunity for clarifying their
      doubts and to reinforce their concepts after lecture classes. Assessment of the
      effect of MCQ preparation by graduate medical students as a revision exercise on
      the topic "Mineral metabolism." At the end of regular teaching module on the
      topic "Mineral metabolism," graduate medical students were asked to prepare the
      stems of 15 MCQs based on the four discriminators given for each. They were told
      that one of the discriminators could be the answer for the MCQ and the remaining
      three could be the distracters. They were further guided in their task by
      providing few key word(s) in the stem of the expected MCQ. In the first phase of
      the exercise, the students attempted the MCQ preparation individually without
      peer consultation. In the second phase, the students participated in small group
      discussion to formulate the best MCQs of the group. The effects on low, medium,
      and high achievers were evaluated by pre and post-tests with the same set of
      MCQs. Both the individual endeavor in Phase 1 and small group discussion in Phase
      2 for the formulation of MCQs significantly contributed to the gain from the
      exercise. The gains from the individual task and from small group discussion were
      equal among the different categories of students. Both phases of the exercise
      were equally beneficial for the low, medium, and high achievers. The high and
      medium achievers retained the gain from the exercise even after 1 week of the
      exercise whereas the low achievers could not retain the gain completely.
      Formulation of MCQs is an effective and useful unconventional revision exercise
      in Biochemistry for graduate medical students.

PMID- 22615225
TI  - An inquiry-based practical for a large, foundation-level undergraduate laboratory
      that enhances student understanding of basic cellular concepts and scientific
      experimental design.
AB  - Student-centered education involving research experiences or inquiry have been
      shown to help undergraduate students understand, and become excited about, the
      process of scientific investigation. These benefits are particularly important
      for students in the early stages of their degree (Report and Kenny,
      http://naplesccsunysbedu/Pres/boyernsf/1998). However, embedding such experiences
      into the curriculum is particularly difficult when dealing with early stage
      students, who are in larger cohorts and often lack the background content
      knowledge necessary to engage with primary research literature and research level
      methods and equipment. We report here the design, delivery, assessment, and
      subsequent student learning outcomes of a 4-week practical module for 120
      students at the beginning of their second year of university, which successfully
      engages students in designing cell culture experiments and in understanding the
      molecular processes and machinery involved in the basic cellular process of
      macropinocytosis.

PMID- 22615226
TI  - Gene expression analysis: teaching students to do 30,000 experiments at once with
      microarray.
AB  - Genome scale experiments routinely produce large data sets that require
      computational analysis, yet there are few student-based labs that illustrate the
      design and execution of these experiments. In order for students to understand
      and participate in the genomic world, teaching labs must be available where
      students generate and analyze large data sets. We present a microarray-based gene
      expression analysis experiment that is tailored for undergraduate students. The
      methods in this article describe an expression analysis experiment that can also
      be applied to CGH and SNP experiments. Factors such as technical difficulty,
      duration, cost, and availability of materials and equipments are considered in
      the lab design. The microarray teaching lab is performed in two sessions. The
      first is an introductory wet bench exercise that allows students to master the
      basic technical skills. The second builds on the concepts and skills with
      students acquiring and analyzing the microarray data. This lab exercise
      familiarizes students with large-scale data experiments and introduces them to
      the initial analysis steps.

PMID- 22615227
TI  - Inquiry-based examination of chemical disruption of bacterial biofilms.
AB  - Inquiry-based instruction in the sciences has been demonstrated as a successful
      educational strategy to use for both high school and college science classrooms.
      As participants in the NSF Graduate STEM Fellows in K-12 Education (GK-12)
      Program, we were tasked with creating novel inquiry-based activities for high
      school classrooms. As a way to introduce microbiology, molecular biology,
      ecology, and human health to students, we created a laboratory activity involving
      formation of biofilms composed of environmental bacteria from pond water and
      investigation into the resistance of these biofilms to antimicrobial agents. Two
      high schools participated in this study in different ways. Pike High School
      biology and advanced environmental science classrooms obtained pond water samples
      and grew biofilms from the bacteria in the pond water on plastic plates. They
      also observed killing of these biofilms by common household antimicrobial agents.
      As a senior capstone project, students at Arsenal Technical High School built on
      these research findings by isolating two different bacterial strains from the
      pond water and demonstrating the stimulatory effect of ethanol on biofilms formed
      by isolated bacterial strains. These activities were successful at introducing
      complex biological topics to high school students in a unique and exciting way.
      The students scored significantly higher on postactivity surveys compared with
      preactivity surveys that measured microbiology knowledge and experimental design
      knowledge. Furthermore, these projects seemed to elicit an excitement for science
      in the students who participated.

PMID- 22615228
TI  - Inexpensive and safe DNA gel electrophoresis using household materials.
AB  - Gel electrophoresis is the single most important molecular biology technique and
      it is central to life sciences research, but it is often too expensive for the
      secondary science classroom or homeschoolers. A simple safe low-cost procedure is
      described here that uses household materials to construct and run DNA gel
      electrophoresis. Plastic containers are fitted with aluminum foil electrodes and
      9-V batteries to run food-grade agar-agar gels using aquarium pH buffers and then
      stained with gentian violet. This activity was tested in a high school biology
      classroom with significantly positive responses on postactivity reflective
      surveys. The electrophoresis activity addresses several Life Science Content
      Standard C criteria, including aspects of cell biology, genetics, and evolution.
      It also can be used to teach aspects of motion and force in the physical science
      classroom.

PMID- 22615229
TI  - Integration of basic sciences in health's courses.
AB  - Concepts from disciplines such as Biochemistry, Genetics, Cellular and Molecular
      Biology are essential to the understanding and treatment of an elevated number of
      illnesses, but often they are studied separately, with no integration between
      them. This article proposes a model for basic sciences integration based on
      problem-based learning (PBL) and compares failure rate, global final grade,
      approved student final grade, grade distribution and students' satisfaction with
      teacher conduction between integrated curriculum and traditional learning in
      health courses from Anhembi Morumbi University-a private institution from Brazil.
      Comparison between integrated and traditional curriculum was based on students'
      records obtained from first-year health sciences students. A total of 1,697
      records from 2005 to 2007 (nonintegrated curriculum) and 785 records from 2008
      (integrated curriculum) were selected for this study and they were necessary to
      get information about students' grades. Moreover, a questionnaire was applied in
      order to cover student's satisfaction with teacher conduction. The data presented
      in this study indicated that the integrated curriculum based on PBL was related
      to an improvement in student's grades and satisfaction compared with traditional
      teaching. We believe that the effectiveness in health education will be a
      combination of "classical" presentation of contents associated to actively
      involved students in the educational process and methodology based on problems in
      order to create the stimulus for the undergraduates continue to integrate basic
      and clinical investigation.

PMID- 22615230
TI  - The Meselson-Stahl experiment.
AB  - Terms to be familiar with before you start to solve the test: DNA replication,
      nitrogen isotopes, density labeling, cesium chloride density gradient
      centrifugation, ultraviolet absorption, DNA denaturation, circular and linear
      DNA, superspiralization, superhelical DNA, and template.

PMID- 22615231
TI  - Commentary: synchronous and asynchronous learning.

PMID- 22615234
TI  - Optimizing siRNA efficacy through alteration in the target cell-adhesion
      substrate interaction.
AB  - The clinical potential of short interfering RNA (siRNA) based therapeutics
      remains hindered by the challenge of delivering enough siRNA into the cytoplasm
      to yield a clinically relevant effect. Although much research has focused on
      optimizing delivery vehicles for this class of molecules, considerably less is
      known about the microenvironmental influences on the response of target cells to
      siRNA. The substrate to which cells adhere is one component of the
      microenvironment that can modulate cellular behavior. Here, we tested the
      hypothesis that modulating the properties of cellular adhesion substrates can
      alter siRNA efficacy. Specifically, cationic lipid complexed siRNA particles were
      applied to U251 cells seeded on alginate hydrogel surfaces with systematic
      variation in elastic modulus and integrin ligand arginine-glycine-aspartate (RGD)
      peptide density. These experiments revealed no change in siRNA-mediated eGFP
      knockdown over the elastic modulus range tested (53-133 kPa). However, an
      eightfold increase in RGD content of the alginate growth substrate resulted in an
      increase in siRNA knockdown efficacy from 25 +/- 12% to 52 +/- 10%, a more than
      twofold increase in silencing. Our results identify control of the cell-adhesion
      substrate interaction as a modulator of siRNA protein silencing efficacy.

PMID- 22615235
TI  - Analysis of density-dependent binding of glycans by lectins using carbohydrate
      microarrays.
AB  - To investigate the density-dependent binding of glycans by lectins using
      carbohydrate microarrays, a number of C-terminal hydrazide-conjugated
      neoglycopeptides with various valences and different spatial arrangements of the
      sugar ligands were prepared on a solid support. The synthetic strategy includes
      (1) assembly of alkyne-linked peptides possessing C-terminal hydrazide on a solid
      support, (2) coupling of azide-linked, unprotected sugars to the alkyne-linked
      peptides on the solid support utilizing click chemistry, and (3) release of the
      neoglycopeptides from the solid support. By using this synthetic methodology,
      sixty five neoglycopeptides with a valency ranging from 1 to 4 and different
      spatial arrangements of the carbohydrate ligands were generated. Carbohydrate
      microarrays were constructed by immobilizing the prepared neoglycopeptides on
      epoxide-derivatized glass slides and were used to analyze the density-dependent
      binding of glycans by lectins. The results of binding property determinations
      show that lectin binding is highly dependent on the surface glycan density.

PMID- 22615236
TI  - Aminocatalytic enantioselective 1,6 additions of alkyl thiols to cyclic dienones:
      vinylogous iminium ion activation.
AB  - Remote transmission: In the presence of chiral amines, 2,4-dienones are activated
      toward the attack of a nucleophile at the delta position, a mode of activation
      that is termed vinylogous iminium ion catalysis. Specifically, the 1,6 addition
      of alkyl thiols to beta-substituted cyclic dienones was catalyzed by a cinchona
      based primary amine; the reaction was highly stereoselective and displayed high
      selectivity for reaction at the delta position.

PMID- 22615237
TI  - Selective synthesis and derivatization of alkali metal silanides MSi(SiH3)3.
AB  - Greetings from silicon valley: Alkali metal silanides (H(3)Si)(3)Si(-)M(+) were
      shown to be selectively accessible for the first time by the reaction of
      neopentasilane Si(SiH(3))(4) with tBuOM or iPr(2)NLi. The method allows the
      convenient derivatization of higher silicon hydrides and provides a simple access
      for unprecedented systematic studies on the chemical behavior of hydropolysilanes
      (see scheme).

PMID- 22615238
TI  - Uncommon chronic cough caused by tracheobronchopathia osteochondroplastica.

PMID- 22615239
TI  - Simultaneous enantioselective separation of polychlorinated biphenyls and their
      methyl sulfone metabolites by heart-cut MDGC: determination of enantiomeric
      fractions in fish oils and cow liver samples.
AB  - The potential of three capillary columns based on beta-cyclodextrin (i.e.,
      Chirasil-Dex, BGB-172, and BGB-176SE) has been studied for the simultaneous
      enantiomeric separation of polychlorinated biphenyls (PCBs) and methylsulfonyl
      metabolites of PCBs (MeSO(2)-PCBs) employing a heart-cut multidimensional gas
      chromatographic system (heart-cut MDGC). Among the columns studied, the BGB-176SE
      capillary column provided the best results, allowing the simultaneous
      enantioselective resolution of six MeSO(2)-PCBs and six chiral PCBs; the Chirasil
      Dex column did not resolve any of the studied MeSO(2)-PCBs; and a poor resolution
      was obtained for three MeSO(2)-PCBs when the BGB-172 column was employed. The
      developed method was successfully applied to two fish oil and one cow liver
      samples commercially available, which showed different enantioselective pattern.
      PCBs 91 and 176 presented a clear enrichment of the second eluted atropisomer in
      codfish oil, whereas in fish oil sample, slight enrichment of the first eluted
      atropisomer of CB45 and the second eluted atropisomer of CB136 were observed.

PMID- 22615240
TI  - Iatrogenic pulmonary artery rupture during Swan-Ganz catheter placement--a novel
      therapeutic approach.
AB  - Pulmonary artery rupture (PAR) is a rare but deadly complication (incidence of
      0.03-0.2% of all PA cannulations), with mortality in the region of 70%. We report
      a case of an 88-year-old woman with iatrogenic PAR as a result of Swan-Ganz
      catheter placement. A rapid successful isolation and occlusion of the culprit PA
      branch via the deployment of an Amplatzer Vascular Plug (AGA Medical Corporation,
      North Plymouth, MN) was performed. To our knowledge, this is the first case
      report where this device has been used as therapy in PAR.

PMID- 22615241
TI  - Intestinal epithelial cells modulate antigen-presenting cell responses to
      bacterial DNA.
AB  - Intestinal epithelial cells and antigen-presenting cells orchestrate mucosal
      innate immunity. This study investigated the role of bacterial DNA in modulating
      epithelial and bone marrow-derived antigen-presenting cells (BM-APCs) and
      subsequent T-lymphocyte responses. Murine MODE-K epithelial cells and BM-APCs
      were treated with DNA from either Bifidobacterium breve or Salmonella enterica
      serovar Dublin directly and under coculture conditions with CD4(+) T cells.
      Apical stimulation of MODE-K cells with S. Dublin DNA enhanced secretion of
      cytokines from underlying BM-APCs and induced interleukin-17 (IL-17) and gamma
      interferon (IFN-gamma) secretion from CD4(+) T cells. Bacterial DNA isolated from
      either strain induced maturation and increased cytokine secretion from BM-APCs.
      Conditioned medium from S. Dublin-treated MODE-K cells elicited an increase in
      cytokine secretion similar to that seen for S. Dublin DNA. Treatment of
      conditioned medium from MODE-K cells with RNase and protease prevented the S.
      Dublin-induced increased cytokine secretion. Oral feeding of mice with B. breve
      DNA resulted in enhanced levels of colonic IL-10 and transforming growth factor
      beta (TGFbeta) compared with what was seen for mice treated with S. Dublin DNA.
      In contrast, feeding mice with S. Dublin DNA increased levels of colonic IL-17
      and IL-12p70. T cells from S. Dublin DNA-treated mice secreted high levels of IL
      12 and IFN-gamma compared to controls and B. breve DNA-treated mice. These
      results demonstrate that intestinal epithelial cells are able to modulate
      subsequent antigen-presenting and T-cell responses to bacterial DNA with
      pathogenic but not commensal bacterial DNA inducing effector CD4(+) T
      lymphocytes.

PMID- 22615243
TI  - Implication of antigenic conversion of Helicobacter pylori lipopolysaccharides
      that involve interaction with surfactant protein D.
AB  - We propose two antigenic types of Helicobacter pylori lipopolysaccharides (LPS):
      highly antigenic epitope-carrying LPS (HA-LPS) and weakly antigenic epitope
      carrying LPS (WA-LPS) based on human serum reactivity. Strains carrying WA-LPS
      are highly prevalent in isolates from gastric cancer patients. WA-LPS exhibits
      more potent biological activities compared to HA-LPS, namely, upregulation of
      Toll-like receptor 4 (TLR4) expression and induction of enhanced epithelial cell
      proliferation. The results of competitive binding assays using monosaccharides
      and methylglycosides, as well as binding assays using glycosidase-treated LPS,
      suggested that beta-linked N-acetyl-D-glucosamine and beta-linked D-galactose
      residues largely contributed to the highly antigenic epitope and the weakly
      antigenic epitope, respectively. WA-LPS exhibited greater binding activity to
      surfactant protein D (SP-D) in a Ca(2+)-dependent manner, and this interaction
      was inhibited by methyl-beta-D-galactoside. The biological activities of WA-LPS
      were markedly enhanced by the addition of SP-D. Lines of evidence suggested that
      removal of beta-N-acetyl-D-glucosamine residue, which comprises the highly
      antigenic epitope, results in exposure of the weakly antigenic epitope. The
      weakly antigenic epitope interacted preferentially with SP-D, and SP-D enhanced
      the biological activity of WA-LPS.

PMID- 22615242
TI  - Role of the vpe carbohydrate permease in Escherichia coli urovirulence and
      fitness in vivo.
AB  - Uropathogenic Escherichia coli (UPEC) strains are a leading cause of infections
      in humans, but the mechanisms governing host colonization by this bacterium
      remain poorly understood. Previous studies have identified numerous gene clusters
      encoding proteins involved in sugar transport, in pathogen-specific islands. We
      investigated the role in fitness and virulence of the vpe operon encoding an EII
      complex of the phosphotransferase (PTS) system, which is found more frequently in
      human strains from infected urine and blood (45%) than in E. coli isolated from
      healthy humans (15%). We studied the role of this locus in vivo, using the UPEC
      E. coli strain AL511, mutants, and complemented derivatives in two experimental
      mouse models of infection. Mutant strains displayed attenuated virulence in a
      mouse model of sepsis. A role in kidney colonization was also demonstrated by
      coinfection experiments in a mouse model of pyelonephritis. Electron microscopy
      examinations showed that the vpeBC mutant produced much smaller amounts of a
      capsule-like surface material than the wild type, particularly when growing in
      human urine. Complementation of the vpeBC mutation led to an increase in the
      amount of exopolysaccharide, resistance to serum killing, and virulence. It was
      therefore clear that the loss of vpe genes was responsible for all the observed
      phenotypes. We also demonstrated the involvement of the vpe locus in gut
      colonization in the streptomycin-treated mouse model of intestinal colonization.
      These findings confirm that carbohydrate transport and metabolism underlie the
      ability of UPEC strains to colonize the host intestine and to infect various host
      sites.

PMID- 22615244
TI  - Antiphagocytic function of an IgG glycosyl hydrolase from Streptococcus equi
      subsp. equi and its use as a vaccine component.
AB  - EndoSe from Streptococcus equi subsp. equi is an enzyme hydrolyzing glycosyl
      groups on IgG, analogous to EndoS from Streptococcus pyogenes. We here show that
      the activity of EndoSe leads to an antiphagocytic function and may thus be a
      contributory factor to immune evasion of S. equi. Despite the damaging effect
      that EndoSe has on IgG, antibodies against EndoSe can neutralize its function.
      Antibodies against EndoSe restored the opsonic activity of specific opsonizing
      antibodies. Mice infected with either S. equi subsp. equi or subsp. zooepidemicus
      or S. pyogenes could be protected by vaccination with EndoSe. It is speculated
      that EndoSe could be a suitable vaccine candidate against streptococcal
      infections.

PMID- 22615245
TI  - A chimeric toxin vaccine protects against primary and recurrent Clostridium
      difficile infection.
AB  - The global emergence of Clostridium difficile infection (CDI) has contributed to
      the recent surge in severe antibiotic-associated diarrhea and colonic
      inflammation. C. difficile produces two homologous glucosylating exotoxins, TcdA
      and TcdB, both of which are pathogenic and require neutralization to prevent
      disease occurrence. However, because of their large size and complex
      multifunctional domain structures, it has been a challenge to produce native
      recombinant toxins that may serve as vaccine candidates. Here, we describe a
      novel chimeric toxin vaccine that retains major neutralizing epitopes from both
      toxins and confers complete protection against primary and recurrent CDI in mice.
      Using a nonpathogenic Bacillus megaterium expression system, we generated
      glucosyltransferase-deficient holotoxins and demonstrated their loss of toxicity.
      The atoxic holotoxins induced potent antitoxin neutralizing antibodies showing
      little cross-immunogenicity or protection between TcdA and TcdB. To facilitate
      simultaneous protection against both toxins, we generated an active clostridial
      toxin chimera by switching the receptor binding domain of TcdB with that of TcdA.
      The toxin chimera was fully cytotoxic and showed potent proinflammatory
      activities. This toxicity was essentially abolished in a glucosyltransferase
      deficient toxin chimera, cTxAB. Parenteral immunization of mice or hamsters with
      cTxAB induced rapid and potent neutralizing antibodies against both toxins.
      Complete and long-lasting disease protection was conferred by cTxAB vaccinations
      against both laboratory and hypervirulent C. difficile strains. Finally,
      prophylactic cTxAB vaccination prevented spore-induced disease relapse, which
      constitutes one of the most significant clinical issues in CDI. Thus, the
      rational design of recombinant chimeric toxins provides a novel approach for
      protecting individuals at high risk of developing CDI.

PMID- 22615246
TI  - Fine specificity of Plasmodium vivax Duffy binding protein binding engagement of
      the Duffy antigen on human erythrocytes.
AB  - Plasmodium vivax invasion of human erythrocytes requires interaction of the P.
      vivax Duffy binding protein (PvDBP) with its host receptor, the Duffy antigen
      (Fy) on the erythrocyte surface. Consequently, PvDBP is a leading vaccine
      candidate. The binding domain of PvDBP lies in a cysteine-rich portion of the
      molecule called region II (PvDBPII). PvDBPII contains three distinct subdomains
      based upon intramolecular disulfide bonding patterns. Subdomain 2 (SD2) is highly
      polymorphic and is thought to contain many key residues for binding to Fy, while
      SD1 and SD3 are comparatively conserved and their role in Fy binding is not well
      understood. To examine the relative contributions of the different subdomains to
      binding to Fy and their abilities to elicit strain-transcending binding
      inhibitory antibodies, we evaluated recombinant proteins from SD1+2, SD2, SD3,
      and SD3+, which includes 24 residues of SD2. All of the recombinant subdomains,
      except for SD2, bound variably to human erythrocytes, with constructs containing
      SD3 showing the best binding. Antisera raised in laboratory animals against SD3,
      SD3+, and SD2+3 inhibited the binding of full-length PvDBPII, which is strain
      transcending, whereas antisera generated to SD1+2 and SD2 failed to generate
      blocking antibodies. All of the murine monoclonal antibodies generated to full
      length PvDBPII that had significant binding-inhibitory activity recognized only
      SD3. Thus, SD3 binds Fy and elicits blocking antibodies, indicating that it
      contains residues critical to Fy binding that could be the basis of a strain
      transcending candidate vaccine against P. vivax.

PMID- 22615247
TI  - Design of meningococcal factor H binding protein mutant vaccines that do not bind
      human complement factor H.
AB  - Meningococcal factor H binding protein (fHbp) is a human species-specific ligand
      for the complement regulator, factor H (fH). In recent studies, fHbp vaccines in
      which arginine at position 41 was replaced by serine (R41S) had impaired fH
      binding. The mutant vaccines elicited bactericidal responses in human fH
      transgenic mice superior to those elicited by control fHbp vaccines that bound
      human fH. Based on sequence similarity, fHbp has been classified into three
      variant groups. Here we report that although R41 is present in fHbp from variant
      groups 1 and 2, the R41S substitution eliminated fH binding only in variant group
      1 proteins. To identify mutants in variant group 2 with impaired fH binding, we
      generated fHbp structural models and predicted 63 residues influencing fH
      binding. From these, we created 11 mutants with one or two amino acid
      substitutions in a variant group 2 protein and identified six that decreased fH
      binding. Three of these six mutants retained conformational epitopes recognized
      by all six anti-fHbp monoclonal antibodies (MAbs) tested and elicited serum
      complement-mediated bactericidal antibody titers in wild-type mice that were not
      significantly different from those obtained with the control vaccine. Thus, fHbp
      amino acid residues that affect human fH binding differ across variant groups.
      This result suggests that fHbp sequence variation induced by immune selection
      also affects fH binding motifs via coevolution. The three new fHbp mutants from
      variant group 2, which do not bind human fH, retained important epitopes for
      eliciting bactericidal antibodies and may be promising vaccine candidates.

PMID- 22615248
TI  - Fur-regulated iron uptake system of Edwardsiella ictaluri and its influence on
      pathogenesis and immunogenicity in the catfish host.
AB  - The ability of bacterial pathogens to take up iron from the host during infection
      is necessary for their multiplication within the host. However, host high
      affinity iron binding proteins limit levels of free iron in fluids and tissues.
      To overcome this deficiency of iron during infection, bacterial pathogens have
      developed iron uptake systems that are upregulated in the absence of iron,
      typically tightly controlled by the ferric uptake regulator (Fur) protein. The
      iron uptake system of Edwardsiella ictaluri, a host-restricted pathogen of
      channel catfish (Ictalurus punctatus) and the main pathogen of this fish in
      aquaculture, is unknown. Here we describe the E. ictaluri Fur protein, the iron
      uptake machinery controlled by Fur, and the effects of fur gene deletion on
      virulence and immunogenicity in the fish host. Analysis of the E. ictaluri Fur
      protein shows that it lacks the N-terminal region found in the majority of
      pathogen-encoded Fur proteins. However, it is fully functional in regulated genes
      encoding iron uptake proteins. E. ictaluri grown under iron-limited conditions
      upregulates an outer membrane protein (HemR) that shows heme-hemoglobin transport
      activity and is tightly regulated by Fur. In vivo studies showed that an E.
      ictaluri Deltafur mutant is attenuated and immune protective in zebrafish (Danio
      rerio) and catfish (Ictalurus punctatus), triggering systemic immunity. We
      conclude that an E. ictaluri Deltafur mutant could be an effective component of
      an immersion-oral vaccine for the catfish industry.

PMID- 22615249
TI  - Role of mouse peptidoglycan recognition protein PGLYRP2 in the innate immune
      response to Salmonella enterica serovar Typhimurium infection in vivo.
AB  - Peptidoglycan recognition proteins (PGRPs) are a family of innate pattern
      recognition molecules that bind bacterial peptidoglycan. While the role of PGRPs
      in Drosophila innate immunity has been extensively studied, how the four
      mammalian PGRP proteins (PGLYRP1 to PGLYRP4) contribute to host defense against
      bacterial pathogens in vivo remains poorly understood. PGLYRP1, PGLYRP3, and
      PGLYRP4 are directly bactericidal in vitro, whereas PGLYRP2 is an N-acetylmuramyl
      L-alanine amidase that cleaves peptidoglycan between the sugar backbone and the
      peptide stem. Because PGLYRP2 cleaves muramyl peptides detected by host
      peptidoglycan sensors Nod1 and Nod2, we speculated that PGLYRP2 may act as a
      modifier of Nod1/Nod2-dependent innate immune responses. We investigated the role
      of PGLYRP2 in Salmonella enterica serovar Typhimurium-induced colitis, which is
      regulated by Nod1/Nod2 through the induction of an early Th17 response. PGLYRP2
      did not contribute to expression of Th17-associated cytokines, interleukin-22 (IL
      22)-dependent antimicrobial proteins, or inflammatory cytokines. However, we
      found that Pglyrp2-deficient mice displayed significantly enhanced inflammation
      in the cecum at 72 h postinfection, reflected by increased polymorphonuclear
      leukocyte (PMN) infiltration and goblet cell depletion. Pglyrp2 expression was
      also induced in the cecum of Salmonella-infected mice, and expression of green
      fluorescent protein under control of the Pglyrp2 promoter was increased in
      discrete populations of intraepithelial lymphocytes. Lastly, Nod2(-/-) Pglyrp2(-/
      ) mice displayed increased susceptibility to infection at 24 h postinfection
      compared to Pglyrp2(-/-) mice, which correlated with increased PMN infiltration
      and submucosal edema. Thus, PGLYRP2 plays a protective role in vivo in the
      control of S. Typhimurium infection through a Nod1/Nod2-independent mechanism.

PMID- 22615250
TI  - The rickettsial OmpB beta-peptide of Rickettsia conorii is sufficient to
      facilitate factor H-mediated serum resistance.
AB  - Pathogenic species of the spotted fever group Rickettsia are subjected to
      repeated exposures to the host complement system through cyclic infections of
      mammalian and tick hosts. The serum complement machinery is a formidable obstacle
      for bacteria to overcome if they endeavor to endure this endozoonotic cycle. We
      have previously demonstrated that that the etiologic agent of Mediterranean
      spotted fever, Rickettsia conorii, is susceptible to complement-mediated killing
      only in the presence of specific monoclonal antibodies. We have also shown that
      in the absence of particular neutralizing antibody, R. conorii is resistant to
      the effects of serum complement. We therefore hypothesized that the interactions
      between fluid-phase complement regulators and conserved rickettsial outer
      membrane-associated proteins are critical to mediate serum resistance. We
      demonstrate here that R. conorii specifically interacts with the soluble host
      complement inhibitor, factor H. Depletion of factor H from normal human serum
      renders R. conorii more susceptible to C3 and membrane attack complex deposition
      and to complement-mediated killing. We identified the autotransporter protein
      rickettsial OmpB (rOmpB) as a factor H ligand and further demonstrate that the
      rOmpB beta-peptide is sufficient to mediate resistance to the bactericidal
      properties of human serum. Taken together, these data reveal an additional
      function for the highly conserved rickettsial surface cell antigen, rOmpB, and
      suggest that the ability to evade complement-mediated clearance from the
      hematogenous circulation is a novel virulence attribute for this class of
      pathogens.

PMID- 22615251
TI  - Comparative analysis of the interaction of Helicobacter pylori with human
      dendritic cells, macrophages, and monocytes.
AB  - Helicobacter pylori may cause chronic gastritis, gastric cancer, or lymphoma.
      Myeloid antigen-presenting cells (APCs) are most likely involved in the induction
      and expression of the underlying inflammatory responses. To study the interaction
      of human APC subsets with H. pylori, we infected monocytes, monocyte-derived
      dendritic cells (DCs), and monocyte-derived (classically activated; M1)
      macrophages with H. pylori and analyzed phenotypic alterations, cytokine
      secretion, phagocytosis, and immunostimulation. Since we detected CD163(+)
      (alternatively activated; M2) macrophages in gastric biopsy specimens from H.
      pylori-positive patients, we also included monocyte-derived M2 macrophages in the
      study. Upon H. pylori infection, monocytes secreted interleukin-1beta (IL-1beta),
      IL-6, IL-10, and IL-12p40 (partially secreted as IL-23) but not IL-12p70.
      Infected DCs became activated, as shown by the enhanced expression of CD25, CD80,
      CD83, PDL-1, and CCR7, and secreted IL-1beta, IL-6, IL-10, IL-12p40, IL-12p70,
      and IL-23. However, infection led to significantly downregulated CD209 and
      suppressed the constitutive secretion of macrophage migration inhibitory factor
      (MIF). H. pylori-infected M1 macrophages upregulated CD14 and CD32, downregulated
      CD11b and HLA-DR, and secreted mainly IL-1beta, IL-6, IL-10, IL-12p40, and IL-23.
      Activation of DCs and M1 macrophages correlated with increased capacity to induce
      T-cell proliferation and decreased phagocytosis of dextran. M2 macrophages
      upregulated CD14 and CD206 and secreted IL-10 but produced less of the
      proinflammatory cytokines than M1 macrophages. Thus, H. pylori affects the
      functions of human APC subsets differently, which may influence the course and
      the outcome of H. pylori infection. The suppression of MIF in DCs constitutes a
      novel immune evasion mechanism exploited by H. pylori.

PMID- 22615252
TI  - The sphingosine-1-phosphate analogue FTY720 impairs mucosal immunity and
      clearance of the enteric pathogen Citrobacter rodentium.
AB  - The sphingosine-1-phosphate (S1P) analogue FTY720 is therapeutically efficacious
      in multiple sclerosis and in the prevention of transplant rejection. It prevents
      the migration of lymphocytes to sites of pathology by trapping them within the
      peripheral lymph nodes, mesenteric lymph nodes (MLNs), and Peyer's patches.
      However, evidence suggests that its clinical use may increase the risk of mucosal
      infections. We investigated the impact of FTY720 treatment on susceptibility to
      gastrointestinal infection with the mouse enteric pathogen Citrobacter rodentium.
      This attaching and effacing bacterium induces a transient bacterial colitis in
      immunocompetent mice that resembles human infection with pathogenic Escherichia
      coli. FTY720 treatment induced peripheral blood lymphopenia, trapped lymphocytes
      in the MLNs, and prevented the clearance of bacteria when mice were infected with
      luciferase-tagged C. rodentium. FTY720-treated C. rodentium-infected mice had
      enhanced colonic inflammation, with significantly higher colon mass, colon
      histopathology, and neutrophil infiltration than vehicle-infected animals. In
      addition, FTY720-treated infected mice had significantly lower numbers of colonic
      dendritic cells, macrophages, and T cells. Gene expression analysis demonstrated
      that FTY720-treated infected mice had an impaired innate immune response and a
      blunted mucosal adaptive immune response, including Th1 cytokines. The data
      demonstrate that the S1P analogue FTY720 adversely affects the immune response to
      and clearance of C. rodentium.

PMID- 22615253
TI  - The Clostridium difficile spo0A gene is a persistence and transmission factor.
AB  - Clostridium difficile is a major cause of chronic antibiotic-associated diarrhea
      and a significant health care-associated pathogen that forms highly resistant and
      infectious spores. Spo0A is a highly conserved transcriptional regulator that
      plays a key role in initiating sporulation in Bacillus and Clostridium species.
      Here, we use a murine model to study the role of the C. difficile spo0A gene
      during infection and transmission. We demonstrate that C. difficile spo0A mutant
      derivatives can cause intestinal disease but are unable to persist within and
      effectively transmit between mice. Thus, the C. difficile Spo0A protein plays a
      key role in persistent infection, including recurrence and host-to-host
      transmission in mice.

PMID- 22615254
TI  - Neutrophils are essential for containment of Vibrio cholerae to the intestine
      during the proinflammatory phase of infection.
AB  - Cholera is classically considered a noninflammatory diarrheal disease, in
      comparison to invasive enteric organisms, although there is a low-level
      proinflammatory response during early infection with Vibrio cholerae and a strong
      proinflammatory reaction to live attenuated vaccine strains. Using an adult mouse
      intestinal infection model, this study examines the contribution of neutrophils
      to host defense to infection. Nontoxigenic El Tor O1 V. cholerae infection is
      characterized by the upregulation of interleukin-6 (IL-6), IL-10, and macrophage
      inflammatory protein 2 alpha in the intestine, indicating an acute innate immune
      response. Depletion of neutrophils from mice with anti-Ly6G IA8 monoclonal
      antibody led to decreased survival of mice. The role of neutrophils in protection
      of the host is to limit the infection to the intestine and control bacterial
      spread to extraintestinal organs. In the absence of neutrophils, the infection
      spread to the spleen and led to increased systemic levels of IL-1beta and tumor
      necrosis factor alpha, suggesting the decreased survival in neutropenic mice is
      due to systemic shock. Neutrophils were found not to contribute to either
      clearance of colonizing bacteria or to alter the local immune response. However,
      when genes for secreted accessory toxins were deleted, the colonizing bacteria
      were cleared from the intestine, and this clearance is dependent upon
      neutrophils. Thus, the requirement for accessory toxins in virulence is negated
      in neutropenic mice, which is consistent with a role of accessory toxins in the
      evasion of innate immune cells in the intestine. Overall, these data support that
      neutrophils impact disease progression and suggest that neutrophil effectiveness
      can be manipulated through the deletion of accessory toxins.

PMID- 22615256
TI  - Crystal engineering of stable temozolomide cocrystals.
AB  - The antitumor prodrug temozolomide (TMZ) decomposes in aqueous medium of pH>=7
      but is relatively stable under acidic conditions. Pure TMZ is obtained as a white
      powder but turns pink and then brown, which is indicative of chemical
      degradation. Pharmaceutical cocrystals of TMZ were engineered with safe coformers
      such as oxalic acid, succinic acid, salicylic acid, d,l-malic acid, and d,l
      tartaric acid, to stabilize the drug as a cocrystal. All cocrystals were
      characterized by powder X-ray diffraction (PXRD), single crystal X-ray
      diffraction, and FT-IR as well as FT-Raman spectroscopy. Temozolomide cocrystals
      with organic acids (pK(a) 2-6) were found to be more stable than the reference
      drug under physiological conditions. The half-life (T(1/2)) of TMZ-oxalic and TMZ
      salicylic acid measured by UV/Vis spectroscopy in pH 7 buffer is two times longer
      than that of TMZ (3.5 h and 3.6 h vs. 1.7 h); TMZ-succinic acid, TMZ-tartaric
      acid, and TMZ-malic acid also exhibited a longer half-life (2.3, 2.5, and 2.8 h,
      respectively). Stability studies at 40  degrees C and 75 % relative humidity (ICH
      conditions) showed that hydrolytic degradation of temozolomide in the solid state
      started after one week, as determined by PXRD, whereas its cocrystals with
      succinic acid and oxalic acid were intact at 28 weeks, thus confirming the
      greater stability of cocrystals compared to the reference drug. The intrinsic
      dissolution rate (IDR) profile of TMZ-oxalic acid and TMZ-succinic acid
      cocrystals in buffer of pH 7 is comparable to that of temozolomide. Among the
      temozolomide cocrystals examined, those with succinic acid and oxalic acid
      exhibited both an improved stability and a comparable dissolution rate to the
      reference drug.

PMID- 22615255
TI  - Calcification resistance for photooxidatively crosslinked acellular bovine
      jugular vein conduits in right-side heart implantation.
AB  - This study aimed to investigate the effect of decellularization plus
      photooxidative crosslinking and ethanol pretreatment on bioprosthetic tissue
      calcification. Photooxidatively crosslinked acellular (PCA) bovine jugular vein
      conduits (BJVCs) and their photooxidized controls (n = 5 each) were sterilized in
      a graded concentration of ethanol solutions for 4 h, and used to reconstruct dog
      right ventricular outflow tracts. At 1-year implantation, echocardiography showed
      similar hemodynamic performance, but obvious calcification for the photooxidized
      BJVC walls. Further histological examination showed intense calcium deposition
      colocalized with slightly degraded elastic fibers in the photooxidized BJVC
      walls, with sparsely distributed punctate calcification in the valves and other
      areas of walls. But PCA BJVCs had apparent degradation of elastic fibers in the
      walls, with only sparsely distributed punctate calcification in the walls and
      valves. Content assay demonstrated comparable calcium content for the two groups
      at preimplantation, whereas less calcium for the PCA group in the walls and
      similar calcium in the valvular leaflets compared with the photooxidized group at
      1-year retrieval. Elastin content assay presented the conduit walls of PCA group
      had less elastin content at preimplantation, but similar content at 1-year
      retrieval compared with the photooxidized group. Phospholipid analysis showed
      phospholipid extraction by ethanol for the PCA group was more efficacious than
      the photooxidized group. These results indicate that PCA BJVCs resist
      calcification in right-side heart implantation owing to decellularization,
      further photooxidative crosslinking, and subsequent phospholipid extraction by
      ethanol at preimplantation.

PMID- 22615257
TI  - Defying entropy: forming large head-to-tail macrocycles in the gas phase.
AB  - Spectral fingerprints: Collision-induced dissociation (CID) of protonated
      peptides in the gas phase results in linear fragment ions with a five-membered
      oxazolone ring on their C-terminal side. Infrared spectroscopy confirms that
      smaller fragments adopt oxazolone structures. Conversely, in mid-sized and larger
      fragments an isomerization to "head-to-tail" macrocycles is observed (see
      picture).

PMID- 22615258
TI  - Palladium-catalyzed mono-alpha-arylation of acetone with aryl
      imidazolylsulfonates.

PMID- 22615259
TI  - Viscosalines B(1,2) and E(1,2): challenging new 3-alkyl pyridinium alkaloids from
      the marine sponge Haliclona viscosa.
AB  - Four new 3-alkyl pyridinium alkaloids, the viscosalines B(1)  (1 a), B(2)  (1 b),
      E(1)  (2 a), and E(2)  (2 b), were isolated from the Arctic sponge Haliclona
      viscosa. The structure elucidation of these isomeric compounds was challenging
      due to ambiguous fragments that derive during "standard" mass spectrometric
      fragmentation experiments. The final structure elucidation relied on the use of a
      combination of synthesis, liquid chromatography, and mass spectrometry. Three
      different mass spectrometers were used to differentiate between the synthetic
      structural isomers: a time-of-flight (TOF) mass spectrometer and two ion-trap
      mass spectrometers with different ion-transfer technologies (i.e., skimmer versus
      funnel optics). Although at first none of the spectrometers returned spectra that
      permitted structure elucidation, all three mass spectrometers provided analysis
      that successfully differentiated between the isomers after thorough method
      optimization. The use of in-source collision-induced dissociation (CID) with the
      ion trap and TOF instrument returned the most interesting results. The mode of
      fragmentation of the viscosalines under different experimental conditions is
      described herein. After successful optimization of the mass spectrometric method
      applied, the chromatographic method was improved to distinguish the previously
      inseparable isomers. Finally, both the liquid chromatography and mass
      spectrometric methods were applied to the natural products and the results
      compared to those from the synthetic compounds.

PMID- 22615260
TI  - Phosphine-induced walking response of the lesser grain borer (Rhyzopertha
      dominica).
AB  - BACKGROUND: In spite of the intensive worldwide use of phosphine against stored
      product insects, its potential sublethal effects on targeted insect species is
      seldom recognised and may compromise the efficacy of this fumigant, particularly
      against phosphine-resistant insects. Therefore, the behavioural response of three
      populations of the lesser grain borer Rhyzopertha dominica (Coleoptera:
      Bostrichidae) to sublethal phosphine exposure was assessed. RESULTS:
      Concentration-mortality bioassays with phosphine confirmed the resistance status
      of the insect populations studied, with levels of phosphine resistance of 40.8
      fold and 85.7-fold compared with the susceptible population. Regarding walking
      behaviour, determined using a digital video-tracking system, the phosphine
      resistant populations were less active than the susceptible population. In
      addition, sublethal phosphine exposure decreased the walking activity of all
      three populations. CONCLUSION: Phosphine exposure decreased walking activity.
      Such reduced walking activity is likely to lower the respiration rate, thereby
      minimising phosphine uptake. As higher phosphine resistance was also associated
      with reduced walking activity, phosphine-resistant populations may resist
      phosphine fumigation even more efficiently on account of this behavioural trait,
      further aiding their physiological resistance, and should be a matter of concern.

PMID- 22615262
TI  - Macroscopic self-propelled objects.
AB  - Self-propelled systems are currently in the spotlight of the research community.
      We review the progress of the construction of both millimeter- and centimeter
      sized self-propelled macroscopic objects. We will also discuss the various
      sources of energy used by these systems, such as the electromagnetic field,
      electric field, thermal gradient, and chemical energy, and present how these
      millimeter- and centimeter-sized devices can move at velocities of tens cm s(-1)
      and distances of several tens of meters.

PMID- 22615261
TI  - Bioactive glass/polymer composite scaffolds mimicking bone tissue.
AB  - The aim of this work was the preparation and characterization of scaffolds with
      mechanical and functional properties able to regenerate bone. Porous scaffolds
      made of chitosan/gelatin (POL) blends containing different amounts of a bioactive
      glass (CEL2), as inorganic material stimulating biomineralization, were
      fabricated by freeze-drying. Foams with different compositions (CEL2/POL 0/100;
      40/60; 70/30 wt %/wt) were prepared. Samples were crosslinked using genipin (GP)
      to improve mechanical strength and thermal stability. The scaffolds were
      characterized in terms of their stability in water, chemical structure,
      morphology, bioactivity, and mechanical behavior. Moreover, MG63 osteoblast-like
      cells and periosteal-derived stem cells were used to assess their
      biocompatibility. CEL2/POL samples showed interconnected pores having an average
      diameter ranging from 179 +/- 5 MUm for CEL2/POL 0/100 to 136 +/- 5 MUm for
      CEL2/POL 70/30. GP-crosslinking and the increase of CEL2 amount stabilized the
      composites to water solution (shown by swelling tests). In addition, the SBF
      soaking experiment showed a good bioactivity of the scaffold with 30 and 70 wt %
      CEL2. The compressive modulus increased by increasing CEL2 amount up to 2.1 +/-
      0.1 MPa for CEL2/POL 70/30. Dynamical mechanical analysis has evidenced that
      composite scaffolds at low frequencies showed an increase of storage and loss
      modulus with increasing frequency; furthermore, a drop of E' and E" at 1 Hz was
      observed, and for higher frequencies both moduli increased again. Cells displayed
      a good ability to interact with the different tested scaffolds which did not
      modify cell metabolic activity at the analyzed points. MTT test proved only a
      slight difference between the two cytotypes analyzed.

PMID- 22615263
TI  - Silicon nanowires as photoelectrodes for carbon dioxide fixation.

PMID- 22615264
TI  - An efficient approach for preparing giant polypeptide triblock copolymers by
      protein dimerization.
AB  - An efficient and convenient approach for preparing a giant polypeptide
      poly(ethylene oxide) triblock copolymer architecture of defined structure and
      composition is reported. This copolymer consists of two long polypeptide chains
      derived from bovine serum albumin of distinct lengths with stabilizing
      poly(ethylene oxide) side-chains, a connecting poly(ethylene oxide) block, and
      the presence of secondary structure elements along the polypeptide backbone. It
      is synthesized from the abundant plasma protein serum albumin and the polypeptide
      backbone is fully biodegradable. This approach represents a convenient and
      efficient strategy for preparing giant polypeptide-based block copolymers of
      defined structure via a semi-synthetic strategy. Such high-molecular-weight,
      biodegradable copolymers are attractive for various biomedical applications.

PMID- 22615265
TI  - Spontaneous ascending aortic intramural haematoma in a patient on dabigatran.
AB  - A patient on oral anticoagulation with dabigatran presented with chest pain and
      dyspnoea. A CT scan of the chest revealed an intramural haematoma of the
      ascending aorta with a large pericardial effusion. The patient underwent a
      modified Bentall procedure. In the absence of a specific antidote for this novel
      oral anticoagulant medication, even in an emergency situation, successful
      surgical treatment was possible with an aggressive use of available
      prohaemostatic agents.

PMID- 22615266
TI  - Constructing organic D-A-pi-A-featured sensitizers with a quinoxaline unit for
      high-efficiency solar cells: the effect of an auxiliary acceptor on the
      absorption and the energy level alignment.
AB  - Four organic D-A-pi-A-featured sensitizers (TQ1, TQ2, IQ1, and IQ2) have been
      studied for high-efficiency dye-sensitized solar cells (DSSCs). We employed an
      indoline or a triphenylamine unit as the donor, cyanoacetic acid as the
      acceptor/anchor, and a thiophene moiety as the conjugation bridge. Additionally,
      an electron-withdrawing quinoxaline unit was incorporated between the donor and
      the pi-conjugation unit. These sensitizers show an additional absorption band
      covering the broad visible range in solution. The contribution from the
      incorporated quinoxaline was investigated theoretically by using DFT and time
      dependent DFT. The incorporated low-band-gap quinoxaline unit as an auxiliary
      acceptor has several merits, such as decreasing the band gap, optimizing the
      energy levels, and realizing a facile structural modification on several
      positions in the quinoxaline unit. As demonstrated, the observed additional
      absorption band is favorable to the photon-to-electron conversion because it
      corresponds to the efficient electron transitions to the LUMO orbital.
      Electrochemical impedance spectroscopy (EIS) Bode plots reveal that the
      replacement of a methoxy group with an octyloxy group can increase the injection
      electron lifetime by a factor of 2.4. IQ2 and TQ2 can perform well without any co
      adsorbent, successfully suppress the charge recombination from TiO(2) conduction
      band to I(3)(-) in the electrolyte, and enhance the electron lifetime, resulting
      in a decreased dark current and enhanced open circuit voltage (V(oc)) values. By
      using a liquid electrolyte, DSSCs based on dye IQ2 exhibited a broad incident
      photon-to-current conversion efficiency (IPCE) action spectrum and high
      efficiency (eta=8.50 %) with a short circuit current density (J(sc)) of 15.65 mA
      cm(-2), a V(oc) value of 776 mV, a fill factor (FF) of 0.70 under AM 1.5
      illumination (100 mW cm(-2)). Moreover, the overall efficiency remained at 97% of
      the initial value after 1000 h of visible-light soaking.

PMID- 22615267
TI  - Bait aggregation to reduce cost and toxin use in aerial 1080 baiting of small
      mammal pests in New Zealand.
AB  - BACKGROUND: The metabolic toxin sodium fluoroacetate ('compound 1080') is widely
      used for controlling introduced mammalian pests in New Zealand. For large-scale
      operations, 1080 is distributed aerially in bait to kill brushtail possums
      (Trichosurus vulpecula Kerr) and ship rats (Rattus rattus L.). While usually
      successful in reducing pest populations by > 80%, widespread distribution of
      toxic bait is relatively expensive and raises concerns from some members of the
      public. Here, trials with spatial aggregation of baits in forested habitats were
      conducted to determine whether this can reduce toxin usage while maintaining
      operational efficacy. RESULTS: When 1080 baits were aggregated into clusters (by
      hand sowing) or into strips (by precision aerial deployment), indices of possum
      relative abundance were reduced by 92-100%, compared with 73-100% reductions
      using conventional aerial broadcasting, while all methods reduced relative
      abundance indices of rats by 88% or greater. Radio tracking indicated a kill rate
      of > 90% against possums, regardless of bait distribution method. CONCLUSIONS:
      Simply by modifying bait distribution patterns, spatial aggregation can be used
      to maintain the high encounter rate of pests with 1080 bait that is necessary for
      operational efficacy, while reducing current toxin usage by up to 80%. Aggregated
      bait delivery could have relevance for other mammalian pest control scenarios
      internationally.

PMID- 22615269
TI  - An electron-deficient porphyrin tape.
AB  - Hexakis(pentafluorophenyl)-substituted meso-meso-linked Zn(II)-diporphyrin (9),
      which was prepared by the acid-catalyzed cross-condensation of 1,1,2,2
      tetrapyrroethane (5) with dipyrromethane dicarbinol (6), was converted into meso
      meso,beta-beta,beta-beta triply linked Zn(II)-diporphyrin 3 by oxidation with 2,3
      dichloro-5,6-dicyanobenzoquinone (DDQ) and Sc(OTf)(3). Beside the red-shifted
      absorption spectrum and split first oxidation potential that are common to the
      triply-linked Zn(II)-diporphyrins, diporphyrin 3 exhibited considerably improved
      chemical stability owing to a lowered HOMO and good solubility in common organic
      solvents. The two-photon absorption (TPA) cross-section and S(1)-state lifetime
      of compound 3 were 1700 GM and 3.3 ps, respectively.

PMID- 22615268
TI  - Cardiopulmonary hemodynamic responses to the small injection of hemoglobin
      vesicles (artificial oxygen carriers) in miniature pigs.
AB  - Intravenous injection of liposomes into pigs reportedly induces anaphylactoid
      reactions at a small dose, resulting in circulatory disorder. Hemoglobin vesicles
      (HbVs) are artificial oxygen carriers encapsulating Hb solution in liposomes. It
      is not known how pigs respond to HbV injection. We aimed to analyze the
      cardiopulmonary responses to small injections of HbV and empty vesicle (EV) and
      compare them with a conventional liposome (CL) with a different lipid composition
      containing phosphatidylglycerol (PG). PG is known to induce an anaphylactoid
      reaction in pigs. Nine male miniature pigs were used for HbV, EV, and CL
      injections. The anesthetized pig received 0.05 and 0.5 mL/kg of a test fluid for
      the first and second injection with a 70 min interval. Results show that CL
      repeatedly induced significant increases in systemic and pulmonary arterial
      pressures and vascular resistances and decreases in heart rate and cardiac output
      (CO). HbV and EV at the first injection-induced pulmonary hypertension, with
      significantly smaller changes in systemic arterial pressure and CO. No remarkable
      response was visible at the second injection in spite of a larger dosage. Only CL
      repeatedly induced thrombocytopenia, leukocytopenia, and plasma thromboxane B(2)
      increase resulting from complement activation, although HbV and EV showed smaller
      changes. Transmittance electron micrograph of pulmonary intravascular macrophages
      (PIMs) showed phagocytosis of HbV, indicating the possibility that nonspecific
      phagocytosis by PIMs relates to the responses observed after the first injection.
      HbV does not induce a significant anaphylactoid reaction in pigs compared with CL
      because of the different lipid composition.

PMID- 22615271
TI  - Response of imidazolinone-tolerant and -susceptible volunteer oilseed rape
      (Brassica napus L.) to ALS inhibitors and alternative herbicides.
AB  - BACKGROUND: Imidazolinone-tolerant oilseed rape (Brassica napus L.) varieties are
      currently grown in Canada, North America, Chile and Australia with high acreage.
      A Europe-wide introduction has started and will be pushed further for both spring
      and winter varieties. The primary aim of this study was to evaluate the impact of
      imidazolinone tolerance for future volunteer oilseed rape control in subsequent
      crops, particularly winter wheat. RESULTS: A greenhouse bioassay showed cross
      tolerance of imidazolinone-tolerant oilseed rape towards sulfonylureas,
      triazolopyrimidines and sulfonylaminocarbonyltriazolinones (resistance factors
      between 5 and 775), with a homozygous variety expressing a much higher tolerance
      level compared with a heterozygous variety. Calculated ED90 values suitable for
      controlling tolerant plants were always much higher than the recommended
      herbicide dose. Generally, results were confirmed under field conditions, but
      with higher efficacies than expected in some cases (e.g. florasulam). Herbicides
      with an alternative mode of action were found to be effective in controlling
      imidazolinone-tolerant volunteers in subsequent winter wheat crops. CONCLUSION:
      Herbicide strategies have to be adjusted for volunteer control in subsequent
      crops if imidazolinone-tolerant oilseed rape varieties are to be grown. However,
      agronomic tools (harvest date, harvest technique, tillage) should be used
      conscientiously in the first place to keep volunteer oilseed rape densities at
      the lowest possible level.

PMID- 22615272
TI  - Papain-specific activating esters in aqueous dipeptide synthesis.
AB  - Enzymatic peptide synthesis has the potential to be a viable alternative for
      chemical peptide synthesis. Because of the increasing commercial interest in
      peptides, new and improved enzymatic synthesis methods are desirable. In recently
      developed enzymatic strategies such as substrate mimetic approaches and enzyme
      specific activation, use of the guanidinophenyl ester (OGp) group has been shown
      to suffer from some drawbacks. OGp esters are sensitive to spontaneous chemical
      hydrolysis and the group is expensive to synthesize and therefore not suitable
      for large-scale applications. On the basis of earlier computational studies, we
      hypothesized that OGp might be replaceable by simpler ester groups to make the
      enzyme-specific activation approach to peptide bond formation more accessible. To
      this end, a set of potential activating esters (Z-Gly-Act) was designed,
      synthesized, and evaluated. Both the benzyl (OBn) and the dimethylaminophenyl
      (ODmap) esters gave promising results. For these esters, the scope of a model
      dipeptide synthesis reaction under aqueous conditions was investigated by varying
      the amino acid donor. The results were compared with those obtained from a
      previous study of Z-X(AA) -OGp esters. Computational docking analysis of the set
      of esters was performed in order to provide insight into the differences in the
      reactivities of all the potential activating esters. Finally, selected ODmap- and
      OBn-activated amino acids were applied in the synthesis of two biologically
      active dipeptides on preparative scales.

PMID- 22615273
TI  - Extended protection against phlebovirus infection conferred by recombinant
      adenovirus expressing consensus interferon (DEF201).
AB  - Punta Toro virus (PTV; Bunyaviridae, Phlebovirus) is related to Rift Valley fever
      virus (RVFV), a pathogenic agent which causes severe disease in humans and
      livestock primarily in the sub-Saharan region of Africa. The recent range
      expansion of RVFV and the potential for its intentional release into naive
      populations pose a significant threat to public health and agriculture. Studies
      modeling disease in rodents and nonhuman primates have shown that PTV and RVFV
      are highly sensitive to the antiviral effects of alpha interferon (IFN-alpha), an
      important component of the innate antiviral host response. While recombinant IFN
      alpha has high therapeutic value, its utility for the treatment of neglected
      tropical diseases is hindered by its short in vivo half-life and costly
      production of longer-lasting pegylated IFNs. Here, we demonstrate extended
      preexposure protection against lethal PTV challenge following a single intranasal
      administration of DEF201, which is a replication-deficient human adenovirus type
      5 vector engineered to constitutively express consensus IFN-alpha (cIFN-alpha)
      from transduced host cells. DEF201 was also efficacious when administered within
      24 h as a postexposure countermeasure. Serum concentrations of cIFN-alpha could
      be detected as early as 8 h following treatment and persisted for more than 1
      week. The prolonged antiphlebovirus prophylactic effect, low production costs,
      and ease of administration make DEF201 a promising agent for intervention during
      natural disease outbreaks and for countering possible bioterrorist acts.

PMID- 22615274
TI  - Antitubercular activity of disulfiram, an antialcoholism drug, against multidrug-
      and extensively drug-resistant Mycobacterium tuberculosis isolates.
AB  - The antimycobacterial activities of disulfiram (DSF) and diethyldithiocarbamate
      (DDC) against multidrug- and extensively drug-resistant tuberculosis (MDR/XDR-TB)
      clinical isolates were evaluated in vitro. Both DSF and DDC exhibited potent
      antitubercular activities against 42 clinical isolates of M. tuberculosis,
      including MDR/XDR-TB strains. Moreover, DSF showed remarkable bactericidal
      activity ex vivo and in vivo. Therefore, DSF might be a drug repurposed for the
      treatment of MDR/XDR-TB.

PMID- 22615275
TI  - Maraviroc and other HIV-1 entry inhibitors exhibit a class-specific
      redistribution effect that results in increased extracellular viral load.
AB  - HIV entry inhibitors, such as maraviroc (MVC), prevent cell-free viruses from
      entering the cells. In clinical trials, patients who were treated with MVC often
      displayed viral loads that were above the limit of conventional viral load
      detection compared to efavirenz-based regimens. We hypothesize that viruses
      blocked by entry inhibitors may be redistributed to plasma, where they
      artificially increase viral load measurements compared to those with the use of
      antiretroviral drugs (ARVs) that act intracellularly. We infected PM-1 cells with
      CCR5-tropic HIV-1 BaL or CXCR4-tropic HIV-1 NL4-3 in the presence of inhibitory
      concentrations of efavirenz, raltegravir, enfuvirtide, maraviroc, and AMD3100,
      the latter three being entry inhibitors. Supernatant viral load, reverse
      transcriptase enzyme activity, and intracellular nucleic acid levels were
      measured at times up to 24 h postinfection. Infectivity of redistributed dual
      tropic HIV-1 was assessed using TZM-bl cells. Extracellular viral load analysis
      revealed that entry inhibitor-treated cells had higher levels of virus in the
      supernatant than the cells treated with other ARVs at 8 h postinfection. By 24 h,
      the supernatant viral load was still higher for entry inhibitors than other ARVs.
      We observed a correlation between viral load and the step of entry inhibition.
      Dual-tropic virus infectivity was undiminished utilizing the CCR5 coreceptor
      following redistribution by CXCR4 entry inhibition. This in vitro model indicates
      that entry inhibitors exhibit a redistribution effect unseen with intracellular
      ARV drugs. Based on these results, the effectiveness of some entry inhibitors may
      be underestimated if plasma viral load is used as a sole indicator of clinical
      success.

PMID- 22615276
TI  - Novel antibiotics targeting respiratory ATP synthesis in Gram-positive pathogenic
      bacteria.
AB  - Emergence of drug-resistant bacteria represents a high, unmet medical need, and
      discovery of new antibacterials acting on new bacterial targets is strongly
      needed. ATP synthase has been validated as an antibacterial target in
      Mycobacterium tuberculosis, where its activity can be specifically blocked by the
      diarylquinoline TMC207. However, potency of TMC207 is restricted to mycobacteria
      with little or no effect on the growth of other Gram-positive or Gram-negative
      bacteria. Here, we identify diarylquinolines with activity against key Gram
      positive pathogens, significantly extending the antibacterial spectrum of the
      diarylquinoline class of drugs. These compounds inhibited growth of
      Staphylococcus aureus in planktonic state as well as in metabolically resting
      bacteria grown in a biofilm culture. Furthermore, time-kill experiments showed
      that the selected hits are rapidly bactericidal. Drug-resistant mutations were
      mapped to the ATP synthase enzyme, and biochemical analysis as well as drug
      target interaction studies reveal ATP synthase as a target for these compounds.
      Moreover, knockdown of the ATP synthase expression strongly suppressed growth of
      S. aureus, revealing a crucial role of this target in bacterial growth and
      metabolism. Our data represent a proof of principle for using the diarylquinoline
      class of antibacterials in key Gram-positive pathogens. Our results suggest that
      broadening the antibacterial spectrum for this chemical class is possible without
      drifting off from the target. Development of the diarylquinolines class may
      represent a promising strategy for combating Gram-positive pathogens.

PMID- 22615277
TI  - Different biosynthetic pathways to fosfomycin in Pseudomonas syringae and
      Streptomyces species.
AB  - Fosfomycin is a wide-spectrum antibiotic that is used clinically to treat acute
      cystitis in the United States. The compound is produced by several strains of
      streptomycetes and pseudomonads. We sequenced the biosynthetic gene cluster
      responsible for fosfomycin production in Pseudomonas syringae PB-5123.
      Surprisingly, the biosynthetic pathway in this organism is very different from
      that in Streptomyces fradiae and Streptomyces wedmorensis. The pathways share the
      first and last steps, involving conversion of phosphoenolpyruvate to
      phosphonopyruvate (PnPy) and 2-hydroxypropylphosphonate (2-HPP) to fosfomycin,
      respectively, but the enzymes converting PnPy to 2-HPP are different. The genome
      of P. syringae PB-5123 lacks a gene encoding the PnPy decarboxylase found in the
      Streptomyces strains. Instead, it contains a gene coding for a citrate synthase
      like enzyme, Psf2, homologous to the proteins that add an acetyl group to PnPy in
      the biosynthesis of FR-900098 and phosphinothricin. Heterologous expression and
      purification of Psf2 followed by activity assays confirmed the proposed activity
      of Psf2. Furthermore, heterologous production of fosfomycin in Pseudomonas
      aeruginosa from a fosmid encoding the fosfomycin biosynthetic cluster from P.
      syringae PB-5123 confirmed that the gene cluster is functional. Therefore, two
      different pathways have evolved to produce this highly potent antimicrobial
      agent.

PMID- 22615278
TI  - Inducible and constitutive activation of two polymorphic promoter alleles of the
      Candida albicans multidrug efflux pump MDR1.
AB  - Overexpression of the multidrug efflux pump MDR1 confers resistance to the
      antifungal drug fluconazole on Candida albicans. It has been reported that two
      types of MDR1 promoters exist in C. albicans and that homozygosity for the allele
      with higher activity may promote fluconazole resistance. We found that the two
      MDR1 promoter alleles in strain SC5314 were equally well activated by inducing
      chemicals or hyperactive forms of the transcription factors Mrr1 and Cap1, which
      control MDR1 expression. In addition, no loss of heterozygosity at the MDR1 locus
      was observed in MDR1-overexpressing clinical C. albicans strains that developed
      fluconazole resistance during therapy.

PMID- 22615279
TI  - An automated image-based method for rapid analysis of Chlamydia infection as a
      tool for screening antichlamydial agents.
AB  - A major limitation in the identification of novel antichlamydial compounds is the
      paucity of effective methods for large-scale compound screening. The
      immunofluorescence assay is the preferred approach for accurate quantification of
      the intracellular growth of Chlamydia. In this study, an immunofluorescence image
      based method (termed image-based automated chlamydial identification and
      enumeration [iBAChIE]) was customized for fully automated quantification of
      Chlamydia infection using the freely available open-source image analysis
      software program CellProfiler and the complementary data exploration software
      program CellProfiler Analyst. The method yielded enumeration of different species
      and strains of Chlamydia highly comparably to the conventional manual methods
      while drastically reducing the analysis time. The inhibitory capability of
      established antichlamydial activity was also evaluated. Overall, these data
      support that iBAChIE is a highly effective tool for automated quantification of
      Chlamydia infection and assessment of antichlamydial activities of molecules.
      Furthermore, iBAChIE is expected to be amenable to high-throughput screening
      studies for inhibitory compounds and fluorescently labeled molecules to study
      host-pathogen interactions.

PMID- 22615280
TI  - Pharmacodynamics of itraconazole against Aspergillus fumigatus in an in vitro
      model of the human alveolus: perspectives on the treatment of triazole-resistant
      infection and utility of airway administration.
AB  - Itraconazole is used for the prevention and treatment of infections caused by
      Aspergillus fumigatus. An understanding of the pharmacodynamics of itraconazole
      against wild-type and triazole-resistant strains provides a basis for innovative
      therapeutic strategies for treatment of infections. An in vitro model of the
      human alveolus was used to define the pharmacodynamics of itraconazole.
      Galactomannan was used as a biomarker. The effect of systemic and airway
      administration of itraconazole was assessed, as was a combination of itraconazole
      administered to the airway and systemically administered 5FC. Systemically
      administered itraconazole against the wild type induced a concentration-dependent
      decline in galactomannan in the alveolar and endothelial compartments. No
      exposure-response relationships were apparent for the L98H, M220T, or G138C
      mutant. The administration of itraconazole to the airway resulted in comparable
      exposure-response relationships to those observed with systemic therapy. This was
      achieved without detectable concentrations of drug within the endothelial
      compartment. The airway administration of itraconazole resulted in a definite but
      submaximal effect in the endothelial compartment against the L98H mutant. The
      administration of 5FC resulted in a concentration-dependent decline in
      galactomannan in both the alveolar and endothelial compartments. The combination
      of airway administration of itraconazole and systemically administered 5FC was
      additive. Systemic administration of itraconazole is ineffective against Cyp51
      mutants. The airway administration of itraconazole is effective for the treatment
      of wild-type strains and appears to have some activity against the L98H mutants.
      Combination with other agents, such as 5FC, may enable the attainment of near
      maximal antifungal activity.

PMID- 22615281
TI  - Facultative sterol uptake in an ergosterol-deficient clinical isolate of Candida
      glabrata harboring a missense mutation in ERG11 and exhibiting cross-resistance
      to azoles and amphotericin B.
AB  - We identified a clinical isolate of Candida glabrata (CG156) exhibiting
      flocculent growth and cross-resistance to fluconazole (FLC), voriconazole (VRC),
      and amphotericin B (AMB), with MICs of >256, >256, and 32 MUg ml(-1),
      respectively. Sterol analysis using gas chromatography-mass spectrometry (GC-MS)
      revealed that CG156 was a sterol 14alpha-demethylase (Erg11p) mutant, wherein
      14alpha-methylated intermediates (lanosterol was >80% of the total) were the only
      detectable sterols. ERG11 sequencing indicated that CG156 harbored a single-amino
      acid substitution (G315D) which nullified the function of native Erg11p. In
      heterologous expression studies using a doxycycline-regulatable Saccharomyces
      cerevisiae erg11 strain, wild-type C. glabrata Erg11p fully complemented the
      function of S. cerevisiae sterol 14alpha-demethylase, restoring growth and
      ergosterol synthesis in recombinant yeast; mutated CG156 Erg11p did not. CG156
      was culturable using sterol-free, glucose-containing yeast minimal medium
      ((glc)YM). However, when grown on sterol-supplemented (glc)YM (with ergosta 7,22
      dienol, ergosterol, cholestanol, cholesterol, Delta(7)-cholestenol, or
      desmosterol), CG156 cultures exhibited shorter lag phases, reached higher cell
      densities, and showed alterations in cellular sterol composition. Unlike
      comparator isolates (harboring wild-type ERG11) that became less sensitive to FLC
      and VRC when cultured on sterol-supplemented (glc)YM, facultative sterol uptake
      by CG156 did not affect its azole-resistant phenotype. Conversely, CG156 grown
      using (glc)YM with ergosterol (or with ergosta 7,22-dienol) showed increased
      sensitivity to AMB; CG156 grown using (glc)YM with cholesterol (or with
      cholestanol) became more resistant (MICs of 2 and >64 MUg AMB ml(-1),
      respectively). Our results provide insights into the consequences of sterol
      uptake and metabolism on growth and antifungal resistance in C. glabrata.

PMID- 22615282
TI  - MK-5172, a selective inhibitor of hepatitis C virus NS3/4a protease with broad
      activity across genotypes and resistant variants.
AB  - HCV NS3/4a protease inhibitors are proven therapeutic agents against chronic
      hepatitis C virus infection, with boceprevir and telaprevir having recently
      received regulatory approval as add-on therapy to pegylated interferon/ribavirin
      for patients harboring genotype 1 infections. Overcoming antiviral resistance,
      broad genotype coverage, and a convenient dosing regimen are important attributes
      for future agents to be used in combinations without interferon. In this
      communication, we report the preclinical profile of MK-5172, a novel P2-P4
      quinoxaline macrocyclic NS3/4a protease inhibitor currently in clinical
      development. The compound demonstrates subnanomolar activity against a broad
      enzyme panel encompassing major hepatitis C virus (HCV) genotypes as well as
      variants resistant to earlier protease inhibitors. In replicon selections, MK
      5172 exerted high selective pressure, which yielded few resistant colonies. In
      both rat and dog, MK-5172 demonstrates good plasma and liver exposures, with 24-h
      liver levels suggestive of once-daily dosing. When administered to HCV-infected
      chimpanzees harboring chronic gt1a or gt1b infections, MK-5172 suppressed viral
      load between 4 to 5 logs at a dose of 1 mg/kg of body weight twice daily (b.i.d.)
      for 7 days. Based on its preclinical profile, MK-5172 is anticipated to be
      broadly active against multiple HCV genotypes and clinically important resistance
      variants and highly suited for incorporation into newer all-oral regimens.

PMID- 22615283
TI  - Inactivation of Mycobacterium tuberculosis l,d-transpeptidase LdtMt1 by
      carbapenems and cephalosporins.
AB  - The structure of Mycobacterium tuberculosis peptidoglycan is atypical since it
      contains a majority of 3->3 cross-links synthesized by l,d-transpeptidases that
      replace 4->3 cross-links formed by the d,d-transpeptidase activity of classical
      penicillin-binding proteins. Carbapenems inactivate these l,d-transpeptidases,
      and meropenem combined with clavulanic acid is bactericidal against extensively
      drug-resistant M. tuberculosis. Here, we used mass spectrometry and stopped-flow
      fluorimetry to investigate the kinetics and mechanisms of inactivation of the
      prototypic M. tuberculosis l,d-transpeptidase Ldt(Mt1) by carbapenems (meropenem,
      doripenem, imipenem, and ertapenem) and cephalosporins (cefotaxime, cephalothin,
      and ceftriaxone). Inactivation proceeded through noncovalent drug binding and
      acylation of the catalytic Cys of Ldt(Mt1), which was eventually followed by
      hydrolysis of the resulting acylenzyme. Meropenem rapidly inhibited Ldt(Mt1),
      with a binding rate constant of 0.08 MUM(-1) min(-1). The enzyme was unable to
      recover from this initial binding step since the dissociation rate constant of
      the noncovalent complex was low (<0.1 min(-1)) in comparison to the acylation
      rate constant (3.1 min(-1)). The covalent adduct resulting from enzyme acylation
      was stable, with a hydrolysis rate constant of 1.0 * 10(-3) min(-1). Variations
      in the carbapenem side chains affected both the binding and acylation steps,
      ertapenem being the most efficient Ldt(Mt1) inactivator. Cephalosporins also
      formed covalent adducts with Ldt(Mt1), although the acylation reaction was 7- to
      1,000-fold slower and led to elimination of one of the drug side chains.
      Comparison of kinetic constants for drug binding, acylation, and acylenzyme
      hydrolysis indicates that carbapenems and cephems can both be tailored to
      optimize peptidoglycan synthesis inhibition in M. tuberculosis.

PMID- 22615284
TI  - Harmine is a potent antimalarial targeting Hsp90 and synergizes with chloroquine
      and artemisinin.
AB  - Previous studies have shown an antimalarial effect of total alkaloids extracted
      from leaves of Guiera senegalensis from Mali in West Africa. We independently
      observed that the beta-carboline alkaloid harmine obtained from a natural product
      library screen inhibited Plasmodium falciparum heat shock protein 90 (PfHsp90)
      ATP-binding domain. In this study, we confirmed harmine-PfHsp90-specific affinity
      using surface plasmon resonance analysis (dissociation constant [K(d)] of 40
      MUM). In contrast, the related compound harmalol bound human Hsp90 (HsHsp90)
      (K(d) of 224 MUM) more tightly than PfHsp90 (K(d) of 7,010 MUM). Site-directed
      mutagenesis revealed that Arg98 in PfHsp90 is essential for harmine selectivity.
      In keeping with our model indicating that Hsp90 inhibition affords synergistic
      combinations with existing antimalarials, we demonstrated that harmine
      potentiates the effect of chloroquine and artemisinin in vitro and in the
      Plasmodium berghei mouse model. These findings have implications for the
      development of novel therapeutic combinations that are synergistic with existing
      antimalarials.

PMID- 22615285
TI  - Application of a loading dose of colistin methanesulfonate in critically ill
      patients: population pharmacokinetics, protein binding, and prediction of
      bacterial kill.
AB  - A previous pharmacokinetic study on dosing of colistin methanesulfonate (CMS) at
      240 mg (3 million units [MU]) every 8 h indicated that colistin has a long half
      life, resulting in insufficient concentrations for the first 12 to 48 h after
      initiation of treatment. A loading dose would therefore be beneficial. The aim of
      this study was to evaluate CMS and colistin pharmacokinetics following a 480-mg
      (6-MU) loading dose in critically ill patients and to explore the bacterial kill
      following the use of different dosing regimens obtained by predictions from a
      pharmacokinetic-pharmacodynamic model developed from an in vitro study on
      Pseudomonas aeruginosa. The unbound fractions of colistin A and colistin B were
      determined using equilibrium dialysis and considered in the predictions. Ten
      critically ill patients (6 males; mean age, 54 years; mean creatinine clearance,
      82 ml/min) with infections caused by multidrug-resistant Gram-negative bacteria
      were enrolled in the study. The pharmacokinetic data collected after the first
      and eighth doses were analyzed simultaneously with the data from the previous
      study (total, 28 patients) in the NONMEM program. For CMS, a two-compartment
      model best described the pharmacokinetics, and the half-lives of the two phases
      were estimated to be 0.026 and 2.2 h, respectively. For colistin, a one
      compartment model was sufficient and the estimated half-life was 18.5 h. The
      unbound fractions of colistin in the patients were 26 to 41% at clinical
      concentrations. Colistin A, but not colistin B, had a concentration-dependent
      binding. The predictions suggested that the time to 3-log-unit bacterial kill for
      a 480-mg loading dose was reduced to half of that for the dose of 240 mg.

PMID- 22615286
TI  - In vitro analyses of ethanol activity against Candida albicans biofilms.
AB  - Candida albicans is a common cause of catheter-related bloodstream infections (CR
      BSI). Ethanol (EtOH) lock therapy has been attempted despite limited data on
      optimal dose and duration. Concentrations of 35% EtOH or higher for a minimum of
      4 h demonstrated a >99% reduction in mature C. albicans biofilm metabolic
      activity and prevented regrowth. Concentrations of 10% EtOH or higher reduced C.
      albicans biofilm formation by >99%. Further investigation of EtOH lock therapy
      for treatment and prevention of C. albicans CR-BSI is warranted.

PMID- 22615287
TI  - Sustained clinical response as an endpoint in treatment trials of Clostridium
      difficile-associated diarrhea.

PMID- 22615288
TI  - High risk of QT interval prolongation and torsades de pointes associated with
      intravenous quinidine used for treatment of resistant malaria or babesiosis.
AB  - Cardiac toxicity may be associated with drugs used for malaria. Torsades de
      pointes (TdP) is a well-known adverse effect of quinidine when used for atrial
      fibrillation. Intravenous quinidine doses for resistant malaria are 2 to 3 times
      higher than those used for arrhythmias. Among 6 patients receiving quinidine for
      malaria or babesiosis, 4 developed QT interval prolongation and 2 experienced
      TdP. Clinicians should be aware that recommended doses of quinidine for malaria
      carry a high TdP risk.

PMID- 22615290
TI  - Identification of (+)-erythro-mefloquine as an active enantiomer with greater
      efficacy than mefloquine against Mycobacterium avium infection in mice.
AB  - Infection caused by Mycobacterium avium is common in AIDS patients who do not
      receive treatment with highly active antiretroviral therapy (HAART) or who
      develop resistance to anti-HIV therapy. Mefloquine, a racemic mixture used for
      malaria prophylaxis and treatment, is bactericidal against M. avium in mice. MICs
      of (+)-erythro-, (-)-erythro-, (+)-threo-, and (-)-threo-mefloquine were 32
      MUg/ml, 32 MUg/ml, 64 MUg/ml, and 64 MUg/ml, respectively. The postantibiotic
      effect for (+)-erythro-mefloquine was 36 h (MIC) and 41 h for a concentration of
      4* MIC. The mefloquine postantibiotic effect was 25 h (MIC and 4* MIC). After
      baseline infection was established (7 days), the (+)- and (-)-isomers of the
      diastereomeric threo- and erythro-alpha-(2-piperidyl)-2,8-bis(trifluoromethyl)-4
      quinolinemethanol were individually used to orally treat C57BL/6 bg(+)/bg(+)
      beige mice that were infected intravenously with M. avium. Mice were also treated
      with commercial mefloquine and diluent as controls. After 4 weeks of treatment,
      the mice were harvested, and the number of bacteria in spleen and liver was
      determined. Mice receiving (+)- or (-)-threo-mefloquine or (-)-erythro-mefloquine
      had numbers of bacterial load in tissues similar to those of untreated control
      mice at 4 weeks. Commercial mefloquine had a bactericidal effect. However, mice
      given the (+)-erythro-enantiomer for 4 weeks had a significantly greater
      reduction of bacterial load than those given mefloquine. Thus, (+)-erythro
      mefloquine is the active enantiomer of mefloquine against M. avium and perhaps
      other mycobacteria.

PMID- 22615291
TI  - Single-dose phase I study to evaluate the pharmacokinetics of posaconazole in new
      tablet and capsule formulations relative to oral suspension.
AB  - Posaconazole oral suspension, a marketed extended-spectrum triazole with proven
      efficacy as antifungal treatment and prophylaxis, should be taken with food to
      maximize absorption. New tablet and capsule formulations have been developed in
      an attempt to optimize absorption and bioavailability. The aims of this
      exploratory open-label, partially randomized, 2-part, 4-way, single-dose
      crossover study in 16 healthy adults were to characterize pharmacokinetics for
      posaconazole tablet and capsule formulations relative to those for posaconazole
      oral suspension under fasted and fed conditions and to assess safety and
      tolerability. Under fasted conditions, posaconazole exposures (area under the
      curve [AUC]) for the tablet and capsule formulations were similar (mean AUC from
      time zero to infinity [AUC(0-infinity)], tablet A, 11,700 ng . h/ml [coefficient
      of variation {CV}, 26%]; tablet B, 11,300 ng . h/ml [CV, 22%]; capsule, 11,000 ng
      . h/ml [CV, 25%]) and were substantially higher than the exposure for the oral
      suspension (mean AUC(0-infinity), 3,420 ng . h/ml [CV, 44%]). Tablets and capsule
      showed less variability in exposure than the oral suspension. In fed subjects,
      tablets and capsule resulted in similar AUC values (mean AUC(0-infinity), tablet
      A, 11,900 ng . h/ml [23%]; tablet B, 12,400 ng . h/ml [CV, 25%]; capsule, 12,300
      ng . h/ml [CV, 28%]) and slightly higher exposure than the oral suspension (mean
      AUC(0-infinity), 8,750 [CV, 24%]). Median times to the maximum concentration of
      drug in plasma were 4 to 5 h (fasted conditions) and 6 to 8 h (fed conditions).
      Mean half-lives values were similar for all formulations under fed and fasted
      conditions (23.1 to 29.2 h). Consistent with previous data, exposure for the oral
      suspension increased 2.5- to 3-fold when it was given with a high-fat meal.
      Conversely, exposures for tablets and capsule were not markedly affected by food.
      All formulations of posaconazole at 100 mg were safe and well tolerated.

PMID- 22615289
TI  - Adverse effects of antimicrobials via predictable or idiosyncratic inhibition of
      host mitochondrial components.
AB  - This minireview explores mitochondria as a site for antibiotic-host interactions
      that lead to pathophysiologic responses manifested as nonantibacterial side
      effects. Mitochondrion-based side effects are possibly related to the notion that
      these organelles are archaic bacterial ancestors or commandeered remnants that
      have co-evolved in eukaryotic cells; thus, this minireview focuses on
      mitochondrial damage that may be analogous to the antibacterial effects of the
      drugs. Special attention is devoted to aminoglycosides, chloramphenicol, and
      fluoroquinolones and their respective single side effects related to
      mitochondrial disturbances. Linezolid/oxazolidinone multisystemic toxicity is
      also discussed. Aminoglycosides and oxazolidinones are inhibitors of bacterial
      ribosomes, and some of their side effects appear to be based on direct inhibition
      of mitochondrial ribosomes. Chloramphenicol and fluoroquinolones target bacterial
      ribosomes and gyrases/topoisomerases, respectively, both of which are present in
      mitochondria. However, the side effects of chloramphenicol and the
      fluoroquinolones appear to be based on idiosyncratic damage to host mitochondria.
      Nonetheless, it appears that mitochondrion-associated side effects are a
      potential aspect of antibiotics whose targets are shared by prokaryotes and
      mitochondria-an important consideration for future drug design.

PMID- 22615292
TI  - Impact of antibiotic MIC on infection outcome in patients with susceptible Gram
      negative bacteria: a systematic review and meta-analysis.
AB  - The objective of this study was to analyze the impact of MIC values within the
      susceptible range of antibiotics on the outcomes of patients with Gram-negative
      infections. The PubMed and Scopus electronic databases were searched. We
      identified 13 articles (1,469 patients) that studied the impact of antibiotic
      MICs on the outcomes of infections; beta-lactams were studied in 10 of them.
      Infections due to Salmonella enterica strains with high fluoroquinolone MICs were
      associated with more treatment failures than those due to strains with low MICs
      (relative risk [RR], 5.75; 95% confidence interval [CI], 1.77 to 18.71). Among
      non-Salmonella enterobacteriaceae, there was no difference in treatment failures
      depending on the MIC value (RR, 1.18; 95% CI, 0.71 to 1.97); however, a higher
      all-cause mortality was observed for patients infected with strains with high
      MICs (RR, 2.03; 95% CI, 1.05 to 3.92). More treatment failures were observed for
      patients infected with nonfermentative Gram-negative bacilli when strains had
      high MICs (RR, 5.54; 95% CI, 2.72 to 11.27). The mortality rate for patients with
      infections with Gram-negative nonfermentative bacilli with high MICs was also
      higher than for those with low MICs (RR, 2.39; 95% CI, 1.19 to 4.81). The limited
      available data suggest that there is an association between high MICs, within the
      susceptible range, and adverse outcomes for patients with Gram-negative
      infections.

PMID- 22615293
TI  - An integrated approach for identification and target validation of antifungal
      compounds active against Erg11p.
AB  - Systemic life-threatening fungal infections represent a significant unmet medical
      need. Cell-based, phenotypic screening can be an effective means of discovering
      potential novel antifungal compounds, but it does not address target
      identification, normally required for compound optimization by medicinal
      chemistry. Here, we demonstrate a combination of screening, genetic, and
      biochemical approaches to identify and characterize novel antifungal compounds.
      We isolated a set of novel non-azole antifungal compounds for which no target or
      mechanism of action is known, using a screen for inhibition of Saccharomyces
      cerevisiae proliferation. Haploinsufficiency profiling of these compounds in S.
      cerevisiae suggests that they target Erg11p, a cytochrome P450 family member,
      which is the target of azoles. Consistent with this, metabolic profiling in S.
      cerevisiae revealed a buildup of the metabolic intermediates prior to Erg11p
      activity, following compound treatment. Further, human cytochrome P450 is also
      inhibited in in vitro assays by these compounds. We modeled the Erg11p protein
      based on the human CYP51 crystal structure, and in silico docking of these
      compounds suggests that they interact with the heme center in a manner similar to
      that of azoles. Consistent with these docking observations, Candida strains
      carrying azole-resistant alleles of ERG11 are also resistant to the compounds in
      this study. Thus, we have identified non-azole Erg11p inhibitors, using a
      systematic approach for ligand and target characterization.

PMID- 22615294
TI  - Preclinical characterization of JTK-853, a novel nonnucleoside inhibitor of the
      hepatitis C virus RNA-dependent RNA polymerase.
AB  - JTK-853 is a novel piperazine derivative nonnucleoside inhibitor of hepatitis C
      virus (HCV) RNA-dependent RNA polymerase. JTK-853 showed potent inhibitory
      activity against genotype 1 HCV polymerase, with a 50% inhibitory concentration
      in the nanomolar range, and showed potent antiviral activity against the genotype
      1b replicon, with a 50% effective concentration of 0.035 MUM. The presence of
      human serum at up to 40% had little effect on the antiviral activity of JTK-853.
      Structure analysis of HCV polymerase with JTK-853 revealed that JTK-853
      associates with the palm site and beta-hairpin region of HCV polymerase, and JTK
      853 showed decreased antiviral activity against HCV replicons bearing the
      resistance mutations C316Y, M414T, Y452H, and L466V in the palm site region of
      HCV polymerase. JTK-853 showed an additive combination effect with other DAAs
      (direct antiviral agents), such as nucleoside polymerase inhibitor, thumb pocket
      binding nonnucleoside polymerase inhibitor, NS5A inhibitor, and protease
      inhibitor. Collectively, these data demonstrate that JTK-853 is a potent and
      novel nonnucleoside palm site-binding HCV polymerase inhibitor, suggesting JTK
      853 as a potentially useful agent in combination with other DAAs for treatment of
      HCV infections.

PMID- 22615296
TI  - In vitro combination of anidulafungin and voriconazole against intrinsically
      azole-susceptible and -resistant Aspergillus spp.
AB  - In vitro interaction of anidulafungin with voriconazole was tested by a
      microdilution broth checkerboard technique and an agar diffusion method against
      30 Aspergillus clinical isolates belonging to five different species. By using a
      complete inhibition endpoint, indifferent interactions were observed for 97% of
      the isolates by the checkerboard technique (FIC index from 0.5 to 2) and for 100%
      of the isolates by the agar diffusion method (variation of -2 to +1 log(2)
      dilutions).

PMID- 22615295
TI  - HIV gp120 H375 is unique to HIV-1 subtype CRF01_AE and confers strong resistance
      to the entry inhibitor BMS-599793, a candidate microbicide drug.
AB  - BMS-599793 is a small molecule entry inhibitor that binds to human
      immunodeficiency virus type 1 (HIV-1) gp120, resulting in the inhibition of CD4
      dependent entry into cells. Since BMS-599793 is currently considered a candidate
      microbicide drug, we evaluated its efficacy against a number of primary patient
      HIV isolates from different subtypes and circulating recombinant forms (CRFs) and
      showed that activity varied between ~3 rhoM and 7 MUM at 50% effective
      concentrations (EC(50)s). Interestingly, CRF01_AE HIV-1 isolates consistently
      demonstrated natural resistance against this compound. Genotypic analysis of
      >1,600 sequences (Los Alamos HIV sequence database) indicated that a single amino
      acid polymorphism in Env, H375, may account for the observed BMS-599793
      resistance in CRF01_AE HIV-1. Results of site-directed mutagenesis experiments
      confirmed this hypothesis, and in silico drug docking simulations identified a
      drug resistance mechanism at the molecular level. In addition, CRF01_AE viruses
      were shown to be resistant to multiple broadly neutralizing monoclonal
      antibodies. Thus, our results not only provide insight into how Env polymorphisms
      may contribute to entry inhibitor resistance but also may help to elucidate how
      HIV can evade some broadly neutralizing antibodies. Furthermore, the high
      frequency of H375 in CRF01_AE HIV-1, and its apparent nonoccurrence in other
      subtypes, could serve as a means for rapid identification of CRF01_AE infections.

PMID- 22615297
TI  - Cellular pharmacokinetics and intracellular activity against Listeria
      monocytogenes and Staphylococcus aureus of chemically modified and
      nanoencapsulated gentamicin.
AB  - OBJECTIVES: The aim of this study was to investigate different hydrophobic
      gentamicin formulations [gentamicin-bis(2-ethylhexyl) sulfosuccinate (GEN-AOT),
      microstructured GEN-AOT (PCA GEN-AOT) and GEN-AOT-loaded poly(lactide-co
      glycolide) acid (PLGA) nanoparticles (NPs)] in view of improving its therapeutic
      index against intracellular bacteria. The intracellular accumulation, subcellular
      distribution and intracellular activity of GEN-AOT and NPs in different monocytic
      macrophagic cell lines were studied. METHODS: Human THP-1 and murine J774
      phagocytic cells were incubated with GEN-AOT formulations at relevant
      extracellular concentrations [from 1* MIC to 18 mg/L (human C(max))], and their
      intracellular accumulation, subcellular distribution and toxicity were evaluated
      and compared with those of conventional unmodified gentamicin. Intracellular
      activity of the formulations was determined against bacteria showing different
      subcellular localizations, namely Staphylococcus aureus (phagolysosomes) and
      Listeria monocytogenes (cytosol). RESULTS: GEN-AOT formulations accumulated 2
      fold (GEN-AOT) to 8-fold (GEN-AOT NPs) more than gentamicin in phagocytic cells,
      with a predominant subcellular localization in the soluble fraction (cytosol) and
      with no significant cellular toxicity. NP formulations allowed gentamicin to
      exert its intracellular activity after shorter incubation times and/or at lower
      concentrations. With an extracellular concentration of 10* MIC, a 1 log(10)
      decrease in S. aureus intracellular inoculum was obtained after 12 h instead of
      24 h for NPs versus free gentamicin, and a static effect was observed against L.
      monocytogenes at 24 h with NPs, while free gentamicin was ineffective.
      CONCLUSIONS: GEN-AOT formulations yielded a high cellular accumulation,
      especially in the cytosol, which resulted in improved efficacy against both
      intracellular S. aureus and L. monocytogenes.

PMID- 22615303
TI  - Microsatellite markers for Bistorta vivipara (Polygonaceae).
AB  - PREMISE OF THE STUDY: Using genomic shotgun 454 sequencing, 50 candidate
      microsatellite markers were targeted for the arctic-alpine polyploid perennial
      herb Bistorta vivipara to distinguish between individual genets and ramets within
      a population. METHODS AND RESULTS: Out of the 50 markers, 31 were polymorphic for
      seven test samples. We have developed a multiplex protocol for 16 of these
      microsatellite markers. CONCLUSIONS: Our results show that the microsatellite
      markers provide a powerful tool for the research on genetic variation of B.
      vivipara.

PMID- 22615298
TI  - Wall teichoic acid protects Staphylococcus aureus from inhibition by Congo red
      and other dyes.
AB  - OBJECTIVES: Polyanionic polymers, including lipoteichoic acid and wall teichoic
      acid, are important determinants of the charged character of the staphylococcal
      cell wall. This study was designed to investigate the extent to which teichoic
      acid contributes to protection from anionic azo dyes and to identify barriers to
      drug penetration for development of new antibiotics for multidrug-resistant
      Staphylococcus aureus infection. METHODS: We studied antimicrobial activity of
      azo dyes against S. aureus strains with or without inhibition of teichoic acid in
      vitro and in vivo. RESULTS: We observed that inhibition of wall teichoic acid
      expression resulted in an ~1000-fold increase in susceptibility to azo dyes such
      as Congo red, reducing its MIC from >1024 to <4 mg/L. Sensitization occurred when
      the first step in the wall teichoic acid pathway, catalysed by TarO, was
      inhibited either by mutation or by chemical inhibition. In contrast, genetic
      blockade of lipoteichoic acid biosynthesis did not confer Congo red
      susceptibility. Based on this finding, combination therapy was tested using the
      highly synergistic combination of Congo red plus tunicamycin at sub-MIC
      concentrations (to inhibit wall teichoic acid biosynthesis). The combination
      rescued Caenorhabditis elegans from a lethal challenge of S. aureus. CONCLUSIONS:
      Our studies show that wall teichoic acid confers protection to S. aureus from
      anionic azo dyes and related compounds, and its inhibition raises the prospect of
      development of new combination therapies based on this inhibition.

PMID- 22615304
TI  - Microsatellite primers for the endangered aquatic herb, Ottelia acuminata
      (Hydrocharitaceae).
AB  - PREMISE OF THE STUDY: Microsatellite primers were developed in the endangered
      aquatic herb, Ottelia acuminata, to characterize its genetic diversity and
      understand its population structure. METHODS AND RESULTS: Eight polymorphic
      microsatellite markers were developed from two populations of O. acuminata in
      China. The number of alleles per locus ranged from one to 15; the observed and
      expected heterozygosities ranged from 0 to 0.885 and from 0 to 0.888,
      respectively, in the two populations. Selected loci also amplified successfully
      in O. sinensis. CONCLUSIONS: These microsatellite markers will facilitate further
      studies on the conservation genetics and evolutionary history of O. acuminata.

PMID- 22615305
TI  - Polymorphic chloroplast microsatellite loci in Nelumbo (Nelumbonaceae).
AB  - PREMISE OF THE STUDY: To study population genetics, phylogeography, and
      hybridization of Nelumbo (Nelumbonaceae), chloroplast microsatellite markers were
      developed. METHODS AND RESULTS: Seventeen microsatellite loci were identified
      from the chloroplast genomes of N. nucifera and N. lutea. Polymorphisms were
      assessed in three populations of N. nucifera and one population of N. lutea. Nine
      loci were found to be polymorphic in N. nucifera, and all 17 loci were found to
      be polymorphic in N. lutea. In N. nucifera, the number of alleles per locus
      ranged from two to six, and the unbiased haploid diversity per locus ranged from
      0.198 to 0.790. In N. lutea, the number of alleles ranged from two to four, and
      the unbiased haploid diversity per locus ranged from 0.245 to 0.694. CONCLUSIONS:
      The identified chloroplast simple sequence repeat markers will be useful for the
      study of genetic diversity, phylogeography, and identification of Nelumbo
      cultivars.

PMID- 22615306
TI  - Isolation and characterization of microsatellite markers from Clematoclethra
      scandens (Actinidiaceae).
AB  - PREMISE OF THE STUDY: Microsatellite makers were developed for Clematoclethra
      scandens to investigate its population genetics and speciation. METHODS AND
      RESULTS: A total of 36 microsatellite markers were isolated using the Fast
      Isolation by AFLP of Sequences COntaining repeats (FIASCO) method. Their
      polymorphisms were assessed in two natural populations. The results showed that
      30 markers displayed prominent polymorphisms and six markers were monomorphic.
      CONCLUSIONS: These microsatellite loci will facilitate further studies on
      population genetics and speciation of C. scandens.

PMID- 22615307
TI  - Characterization of microsatellite loci from Litsea hypophaea (Lauraceae), a tree
      endemic to Taiwan.
AB  - PREMISE OF THE STUDY: Microsatellite primers were developed for the endemic tree
      Litsea hypophaea (Lauraceae) in Taiwan to investigate its genetic diversity and
      population genetic structure and to investigate species delimitation within
      Litsea. METHODS AND RESULTS: Fifteen new simple sequence repeat markers were
      developed from L. hypophaea with a magnetic bead enrichment method. Most loci
      were also amplified from three closely related species, L. coreana, L. lii, and
      L. acutivena. The number of alleles and observed and expected heterozygosities
      across loci varied with a range of 1-25, 0.000-1.000, and 0.000-0.956,
      respectively. CONCLUSIONS: The application of these microsatellite markers of L.
      hypophaea provides a tool for understanding genetic diversity and population
      differentiation. In addition, interspecific amplification suggests that these
      markers will also be useful for species identification of related taxa within
      Litsea in Taiwan.

PMID- 22615309
TI  - The effect of mammalian herbivory on inflorescence architecture in ornithophilous
      Babiana (Iridaceae): implications for the evolution of a bird perch.
AB  - PREMISE OF THE STUDY: The showiness of floral displays is usually explained as an
      adaptation to attract pollinators. However, selection for less attractive
      displays imposed by non-pollinating agents, particularly herbivores, may balance
      pollinator-driven selection for highly visible inflorescences. We investigated
      whether inflorescence architecture, particularly the unusual ground-level
      flowering associated with a specialized bird perch in Babiana ringens may have
      originated, in part, as an adaptive response to mammalian herbivory. METHODS: We
      measured levels of herbivory by antelope in populations of B. hirsuta, the
      putative sister species of B. ringens, which possesses the likely ancestral form
      of inflorescence architecture. To test for position-dependent effects of
      herbivory on flowers, we compared the herbivory rates and seed production of
      manipulated inflorescences in a field experiment. We predicted that flowers at
      the base of inflorescences would suffer less herbivory than those in apical
      positions. RESULTS: We found herbivore damage to flowers in 50% of naturally
      occurring B. hirsuta plants. Manipulated inflorescences with only basal flowers,
      and consequently similar inflorescence architecture to B. ringens, experienced
      significantly lower herbivory and higher seed set than inflorescences manipulated
      to have only apical flowers. CONCLUSIONS: Our results are consistent with the
      hypothesis that position-dependent herbivory on inflorescences could have played
      a role in the evolution of inflorescence design. More specifically, position
      dependent herbivory may have selected for the loss of apical flowers. Position
      dependent herbivory may have contributed toward the evolution of a naked
      inflorescence axis, a structure that characterizes B. ringens and functions as a
      bird perch facilitating cross-pollination by sunbirds.

PMID- 22615308
TI  - Development of novel chloroplast microsatellite markers for Miscanthus species
      (Poaceae).
AB  - PREMISE OF THE STUDY: A set of novel chloroplast microsatellite markers (cpSSRs)
      was developed for the bioenergy crop Miscanthus, and their utility in cross
      species amplification was evaluated. METHODS AND RESULTS: Twenty-eight novel
      primers flanking cpSSR loci were designed from a complete chloroplast genome
      sequence of Saccharum officinarum, a species closely related to Miscanthus. These
      primers were then tested on eight Miscanthus species, among which 16 cpSSR loci
      were found to be polymorphic. The number of alleles per polymorphic locus ranged
      from two to seven, with an average 3.94 alleles. CONCLUSIONS: These cpSSR markers
      can be applied to all Miscanthus species and will be useful for studying
      Miscanthus population structure, diversity, and phylogeography.

PMID- 22615310
TI  - New silica gel-based monolithic column for nano-liquid chromatography, used in
      the HILIC mode.
AB  - This paper describes the synthesis and chromatographic and morphologic
      characterization of two monolithic silica nano-columns (50 um i.d.) prepared by
      sol-gel processes, using hydrophilic interaction (HILIC) mode separations to
      evaluate their performance. Two types of monoliths were prepared by varying the
      precursors (tetraethoxysilane or a tetraethoxysilane-methyltrimethoxysilane
      mixture) and by changing the type of catalyst (urea and acetic acid or ammonium
      hydroxide). The monoliths were characterized by scanning electron microscopy,
      thermogravimetric analysis, infrared spectroscopy and nitrogen adsorption
      desorption isotherms. The columns were tested for the separation of several
      mixtures, with the organically modified silica (ormosil) column successfully
      separating two challenging mixtures using HILIC conditions.

PMID- 22615311
TI  - Safety and immunogenicity of 2009 pandemic H1N1 influenza vaccination in
      perinatally HIV-1-infected children, adolescents, and young adults.
AB  - BACKGROUND: The safety and immunogenicity of high-dose pandemic H1N1 (pH1N1)
      vaccination in perinatally human immunodeficiency virus type 1 (HIV-1)-infected
      children, adolescents, and young adults are unknown. METHODS: Two 30-MUg doses of
      2009 Novartis pH1N1 monovalent vaccine (Fluvirin) were administered 21-28 days
      apart to perinatally HIV-1-infected children, adolescents, and young adults.
      Antibodies were measured by hemagglutination inhibition (HAI) assay at baseline,
      21-28 days after first vaccination, 7-13 days after the second vaccination, and 7
      months after the first vaccination. RESULTS: Among the 155 participants, 54 were
      aged 4-8 years, 51 were aged 9-17 years, and 50 were aged 18-24 years. After 2
      doses of Fluvirin, seroresponse (>= 4-fold rise in HAI titers) was demonstrated
      in 79.6%, 84.8%, and 83% of participants in the aforementioned age groups,
      respectively, and seroprotection (HAI titers >= 40) was shown in 79.6%, 82.6%,
      and 85.1%, respectively. Of those lacking seroresponse (n = 43) or seroprotection
      (n = 37) after the first vaccination, 46.5% and 40.5% achieved seroresponse or
      seroprotection, respectively, after the second vaccination. Among participants
      who lacked seroprotection at entry, a "complete response" (both seroresponse and
      seroprotection) after first vaccination was associated with higher baseline
      log(10) HAI titer and non-Hispanic ethnicity. No serious vaccine-related events
      occurred. CONCLUSION: Two doses of double-strength pH1N1 vaccine are safe and
      immunogenic and may provide improved protection against influenza in perinatally
      HIV-1-infected children and youth. CLINICAL TRIALS REGISTRATION: NCT00992836.

PMID- 22615313
TI  - Stem bromelain-induced macrophage apoptosis and activation curtail Mycobacterium
      tuberculosis persistence.
AB  - BACKGROUND: Mycobacterium tuberculosis, the causative agent of tuberculosis, has
      a remarkable ability to usurp its host's innate immune response, killing millions
      of infected people annually. One approach to manage infection is prevention
      through the use of natural agents. In this regard, stem bromelain (SBM), a
      pharmacologically active member of the sulfhydryl proteolytic enzyme family,
      obtained from Ananas comosus and possessing a remarkable ability to induce the
      innate and acquired immune systems, is important. METHODS: We evaluated SBM's
      ability to induce apoptosis and free-radical generation in macrophages. We also
      studied antimycobacterial properties of SBM and its effect on foamy macrophages.
      RESULTS: SBM treatment of peritoneal macrophages resulted in the upregulation of
      proapoptotic proteins and downregulation of antiapoptotic proteins. Additionally,
      SBM treatment activated macrophages, curtailed the levels of free glutathione,
      and augmented the production of hydrogen peroxide, superoxide anion,
      peroxynitrite, and nitric oxide. SBM cleaves CD36 and reduced the formation of
      foam cells, the hallmark of M. tuberculosis infection. These conditions created
      an environment for the increased clearance of M. tuberculosis. CONCLUSIONS:
      Together these data provide a mechanism for antimycobacterial activity of SBM and
      provide important insights for the use of cysteine proteases as immunomodulatory
      agents.

PMID- 22615312
TI  - Underrecognized mildly symptomatic viremic dengue virus infections in rural Thai
      schools and villages.
AB  - BACKGROUND: The understanding of dengue virus (DENV) transmission dynamics and
      the clinical spectrum of infection are critical to informing surveillance and
      control measures. Geographic cluster studies can elucidate these features in
      greater detail than cohort studies alone. METHODS: A 4-year longitudinal cohort
      and geographic cluster study was undertaken in rural Thailand. Cohort children
      underwent pre-/postseason serology and active school absence-based surveillance
      to detect inapparent and symptomatic dengue. Cluster investigations were
      triggered by cohort dengue and non-dengue febrile illnesses (positive and
      negative clusters, respectively). RESULTS: The annual cohort incidence of
      symptomatic dengue ranged from 1.3% to 4.4%. DENV-4 predominated in the first 2
      years, DENV-1 in the second 2 years. The inapparent-to-symptomatic infection
      ratio ranged from 1.1:1 to 2.9:1. Positive clusters had a 16.0% infection rate,
      negative clusters 1.1%. Of 119 infections in positive clusters, 59.7% were
      febrile, 20.2% were afebrile with other symptoms, and 20.2% were asymptomatic. Of
      16 febrile children detected during cluster investigations who continued to
      attend school, 9 had detectable viremia. CONCLUSIONS: Dengue transmission risk
      was high near viremic children in both high- and low-incidence years. Inapparent
      infections in the cohort overestimated the rate of asymptomatic infections.
      Ambulatory children with mild febrile viremic infections could represent an
      important component of dengue transmission.

PMID- 22615314
TI  - Identification of strains of RotaTeq rotavirus vaccine in infants with
      gastroenteritis following routine vaccination.
AB  - BACKGROUND: RotaTeq vaccine was introduced into the Australian National
      Immunisation Program in 2007. This study identified and characterised rotavirus
      strains excreted by infants who presented with symptoms of gastroenteritis
      following recent RotaTeq vaccination. METHODS: Fecal samples (N = 61) from
      children who developed gastroenteritis following recent RotaTeq vaccination were
      forwarded to the Australian Rotavirus Surveillance Program (ARSP). RotaTeq
      positive samples were genotyped and regions of the VP3, VP4, VP6, and VP7 genes
      were sequenced. Also, 460 rotavirus-positive ARSP routine surveillance samples
      were analyzed by dot-blot Northern hybridization to detect RotaTeq vaccine
      derived strains circulating in the community. RESULTS: Thirteen of the 61 samples
      collected from infants developing gastroenteritis after RotaTeq vaccination
      contained vaccine-derived (vd) rotavirus strains. Of these, 4 contained a
      vdG1P[8] strain derived by reassortment between the G1P[5] and G6P[8] parental
      vaccine strains. Northern hybridization analysis of 460 surveillance samples
      identified 3 samples that contained RotaTeq vaccine-derived strains, including 2
      vdG1P[8] reassortant vaccine strains. CONCLUSIONS: During replication and
      excretion of RotaTeq vaccine, reassortment of parental strains can occur.
      Shedding of RotaTeq vaccine strains in 7 of 13 infants was associated with
      underlying medical conditions that may have altered their immune function. The
      benefits of vaccination outweigh any small risk of vaccine-associated
      gastroenteritis.

PMID- 22615316
TI  - Hepatitis B virus e antigen physically associates with receptor-interacting
      serine/threonine protein kinase 2 and regulates IL-6 gene expression.
AB  - We previously reported that hepatitis B virus (HBV) e antigen (HBeAg) inhibits
      production of interleukin 6 by suppressing NF-kappaB activation. NF-kappaB is
      known to be activated through receptor-interacting serine/threonine protein
      kinase 2 (RIPK2), and we examined the mechanisms of interleukin 6 regulation by
      HBeAg. HBeAg inhibits RIPK2 expression and interacts with RIPK2, which may
      represent 2 mechanisms through which HBeAg blocks nucleotide-binding
      oligomerization domain-containing protein 1 ligand-induced NF-kappaB activation
      in HepG2 cells. Our findings identified novel molecular mechanisms whereby HBeAg
      modulates intracellular signaling pathways by targeting RIPK2, supporting the
      concept that HBeAg could impair both innate and adaptive immune responses to
      promote chronic HBV infection.

PMID- 22615315
TI  - In vitro-reduced susceptibility to artemether in P. falciparum and its
      association with polymorphisms on transporter genes.
AB  - Plasmodium falciparum with reduced sensitivity to artemisinin derivatives has
      been observed in endemic areas, but the molecular mechanisms for this reduced
      sensitivity remain unclear. We evaluated the association between in vitro
      susceptibility of P. falciparum isolates obtained from southwest Nigeria and
      polymorphisms in selected putative transporter genes (PFE0775C, PF13_0271,
      pfmrp1, pfcrt, and pfmdr1). Modified schizont inhibition assay was used to
      determine the in vitro parasite susceptibility to artemether (ATH). Polymorphisms
      in selected genes were detected by polymerase chain reaction followed by direct
      DNA sequencing. The half-maximal inhibitory concentration (IC(50)) geometric mean
      (GM) for all P. falciparum isolates was 1.78 nM (range, 0.03-10.43 nM).
      Polymorphisms at codons 241, 86, and 76 of PFE0775C, pfmdr1, and pfcrt genes,
      respectively, were associated with reduced susceptibility to ATH. A new S263P
      single-nucleotide polymorphism on the PFE0775C gene was also detected in 27% of
      the isolates. Patient isolates harboring V241L or S263P polymorphisms on the
      PFE0775C gene showed increased IC(50) (GM: 3.08 nM and 1.79 nM, respectively).
      Plasmodium falciparum isolates harboring mutant Y86 pfmdr1 and P263 PFE0775C
      alleles showed a 2.5-5.5-fold increase in ATH IC(50.) This study shows that
      polymorphisms on the PFE0775C and pfmdr1 genes are associated with reduced
      sensitivity to ATH in fresh isolates of P. falciparum from Nigeria.

PMID- 22615318
TI  - Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis
      infections in men with nongonococcal urethritis: predictors and persistence after
      therapy.
AB  - BACKGROUND: Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), and
      Trichomonas vaginalis (TV) are sexually transmitted infections (STIs) associated
      with nongonococcal urethritis (NGU). We assessed their predictors and persistence
      after treatment. METHODS: We analyzed data from an NGU treatment trial among
      symptomatic heterosexual men aged 16-45 years from STI clinics. Nucleic acid
      amplification tests detected CT, MG, and TV at baseline and at 1 and 4 weeks
      after therapy. Associations between variables and STI detection were
      investigated. RESULTS: Among 293 participants, 44% had CT, 31% had MG, and 13%
      had TV at baseline. In multivariate analysis, CT infection was associated with
      young age and STI contact. Young age was also associated with MG, and having >= 1
      new partner was negatively associated with TV. We detected persistent CT in 12%
      and MG in 44% of participants at 4 weeks after therapy, which were associated
      with signs and symptoms of NGU. Persistent CT was detected in 23% of participants
      after azithromycin treatment vs 5% after doxycycline treatment (P = .011);
      persistent MG was detected in 68% of participants after doxycycline vs 33% after
      azithromycin (P = .001). All but 1 TV infection cleared after tinidazole.
      CONCLUSIONS: Persistent CT and MG after treatment of NGU are common, and were
      associated with clinical findings and drug regimen.

PMID- 22615319
TI  - Molecular characterization of the 2011 Hong Kong scarlet fever outbreak.
AB  - A scarlet fever outbreak occurred in Hong Kong in 2011. The majority of cases
      resulted in the isolation of Streptococcus pyogenes emm12 with multiple
      antibiotic resistances. Phylogenetic analysis of 22 emm12 scarlet fever outbreak
      isolates, 7 temporally and geographically matched emm12 non-scarlet fever
      isolates, and 18 emm12 strains isolated during 2005-2010 indicated the outbreak
      was multiclonal. Genome sequencing of 2 nonclonal scarlet fever isolates (HKU16
      and HKU30), coupled with diagnostic polymerase chain reaction assays, identified
      2 mobile genetic elements distributed across the major lineages: a 64.9-kb
      integrative and conjugative element encoding tetracycline and macrolide
      resistance and a 46.4-kb prophage encoding superantigens SSA and SpeC and the
      DNase Spd1. Phenotypic comparison of HKU16 and HKU30 with the S. pyogenes M1T1
      strain 5448 revealed that HKU16 displays increased adherence to HEp-2 human
      epithelial cells, whereas HKU16, HKU30, and 5448 exhibit equivalent resistance to
      neutrophils and virulence in a humanized plasminogen murine model. However, in
      contrast to M1T1, the virulence of HKU16 and HKU30 was not associated with covRS
      mutation. The multiclonal nature of the emm12 scarlet fever isolates suggests
      that factors such as mobile genetic elements, environmental factors, and host
      immune status may have contributed to the 2011 scarlet fever outbreak.

PMID- 22615320
TI  - Human papillomavirus infection and bladder cancer: an alternate perspective from
      a modified meta-analysis.

PMID- 22615321
TI  - Prolonged myalgia in Sindbis virus infection: case description and in vitro
      infection of myotubes and myoblasts.
AB  - BACKGROUND: Sindbis virus (SINV) is a mosquito-borne alphavirus found in Eurasia,
      Africa, and Oceania. Clinical SINV infection is characterized by febrile rash and
      arthritis and sometimes prolonged arthralgia and myalgia. The pathophysiological
      mechanisms of musculoskeletal and rheumatic disease caused by SINV are
      inadequately understood. METHODS: We studied the muscle pathology of SINV
      infection ex vivo by examining a unique muscle biopsy obtained from a patient
      with chronic myalgia and arthralgia 6 months after acute SINV infection and
      assessed potential genetic predisposing factors by determining the human
      leukocyte antigen (HLA) and complement factor C4 genes and proteins. In addition,
      we performed in vitro SINV infections of primary human myoblasts and myotubes.
      RESULTS: In the muscle biopsy we found evidence of muscle regeneration due to
      previous necrotic lesions likely caused by earlier SINV infection. We showed that
      human myoblasts and myotubes were susceptible in vitro for SINV infection as the
      cells became immunoreactive for viral antigens and cytopathic effect was
      observed. The patient was homozygous for HLA-B*35 alleles and heterozygous for
      HLA-DRB1*01 and HLA-DRB1*03 alleles and had total deficiency of C4B protein.
      CONCLUSIONS: This study provides new insights concerning pathological processes
      leading to chronic symptoms in SINV infection and demonstrates for the first time
      the susceptibility of human myogenic cells to SINV infection.

PMID- 22615322
TI  - Efficacy of preerythrocytic and blood-stage malaria vaccines can be assessed in
      small sporozoite challenge trials in human volunteers.
AB  - The development of a vaccine against malaria has public health priority. In a
      controlled setting, preliminary data on the efficacy of Plasmodium falciparum
      vaccine candidates can be obtained by exposing immunized human volunteers to the
      bites of laboratory-reared P. falciparum-infected mosquitoes. Using empirical
      data, we show that these trials, with small numbers of volunteers, are
      sufficiently powered to detect protective biological effects induced by
      preerythrocytic and/or blood-stage candidate vaccines if parasitemia is measured
      daily by quantitative polymerase chain reaction. Sporozoite challenge trials are
      thus a powerful tool for early selection of candidates that warrant efficacy of
      trials in the field.

PMID- 22615323
TI  - Low-level Plasmodium falciparum blood-stage infection causes dendritic cell
      apoptosis and dysfunction in healthy volunteers.
AB  - BACKGROUND: Dendritic cells (DCs) are highly specialized antigen-presenting cells
      that are crucial for initiation of immune responses. During naturally acquired
      malaria, DC number and function is reduced. METHODS: The timing of, parasitemia
      threshold of, and contribution of apoptosis to DC loss were prospectively
      evaluated in 10 men after experimental challenge with approximately 1800
      Plasmodium falciparum-parasitized red blood cells (pRBCs) and after drug cure
      initiated at a parasite level of >= 1000 parasites/mL. RESULTS: The nadir levels
      of total, myeloid, and plasmacytoid DCs occurred 8 days after infection. DC loss
      was partially attributable to apoptosis, which was first detected on day 5
      (median parasite level, 238 parasites/mL) and maximal at day 7. Remaining DCs
      exhibited a reduced ability to uptake particulate antigen. DC numbers recovered
      approximately 60 hours after antimalarial drug administration. There was no loss
      of DC number or function before or after drug cure in 5 men inoculated with <180
      pRBCs and treated on day 6, when their parasite level was approximately 200
      parasites/mL. CONCLUSIONS: Plasmodium causes DC loss in vivo, which is at least
      partially explained by apoptosis in response to blood-stage parasites. In primary
      infection, loss of DC number and function occurs early during the prepatent
      period and before or with onset of clinical symptoms. These findings may explain
      in part the inadequate development of immunity to blood-stage malaria infection.

PMID- 22615324
TI  - Tips for managing a social networking site.

PMID- 22615325
TI  - REFRESH--reducing families' exposure to secondhand smoke in the home: a
      feasibility study.
AB  - OBJECTIVE: To study a novel intervention (REFRESH) aimed at reducing children's
      exposure to secondhand smoke (SHS) in their homes. DESIGN: A randomised
      feasibility study. SETTING: Aberdeen City and Aberdeenshire. PARTICIPANTS: A
      total of 59 smoking mothers with at least one child younger than 6 years.
      Participation took place between July 2010 and March 2011. INTERVENTION: Four
      home visits over a 1-month period, which involved two 24-h measurements of home
      air quality (PM2.5) and a motivational interview to encourage changes to smoking
      behaviour within the home in order to reduce child SHS exposure. The enhanced
      group received their air quality data as part of their motivational interview at
      visit 2; the control group received that information at visit 4. MAIN OUTCOME
      MEASURES: The main outcome measures were comparisons of the data from visits 2
      and 4 on the 24-h average concentration of PM2.5, the peak concentration of
      PM2.5, the percentage of time when household PM2.5 concentrations exceeded a
      health-based threshold of 35 MUg/m(3) and child's salivary cotinine (in nanograms
      per millilitre). The views of the mothers from the enhanced group about their
      understanding of the intervention and the measures used were also analysed to
      assess the acceptability and utility of the intervention. RESULTS: Of the
      recruited 54 participants, 48 completed the study: 27 from the control group and
      21 from the enhanced group. Both groups experienced reductions in PM2.5
      concentrations. When testing paired samples for the enhanced group, there was a
      significant difference (p<0.05) between visit 2 and visit 4 values for maximum
      PM2.5 (p=0.006) and for percentage of time over 35 MUg/m(3) (p=0.017), with
      average PM2.5 approaching significance (p=0.056). There was no significant
      difference for salivary cotinine. The qualitative findings showed that mothers
      were able to understand the data they were shown and were shocked by the values
      measured in their homes despite being aware of the effects of SHS exposure. They
      appreciated the intervention taking place in their homes as it allowed them to
      have personalised data. Many mothers described how they had changed their smoking
      behaviours in their home and in particular were motivated to protect their own
      children as a result of the knowledge they had gained. CONCLUSIONS: Providing
      mothers who smoke with personalised results about the indoor air quality of their
      homes along with a motivational interview is feasible and has an effect on
      improving household air quality. Participants found the intervention
      understandable and acceptable. Taken overall, the results suggest that a future
      large-scale trial using measurements of indoor air quality as part of a complex
      intervention to reduce children's SHS exposure should be explored.

PMID- 22615327
TI  - Gait variability measures reveal differences between multiple sclerosis patients
      and healthy controls.
AB  - The purpose of this study was to determine the differences in gait variability
      between patients with multiple sclerosis (MS) and healthy controls during walking
      at a self-selected pace. METHODS: Kinematics were collected during three minutes
      of treadmill walking for 10 patients with MS and 10 healthy controls. The
      Coefficient of Variation (CoV), the Approximate Entropy (ApEn) and the Detrended
      Fluctuation Analysis (DFA) were used to investigate the fluctuations present in
      stride length and step width from continuous strides. RESULTS: ApEn revealed that
      patients with MS had significantly lower values than healthy controls for stride
      length (p < .001) and step width (p < .001). CONCLUSIONS: ApEn results revealed
      that the natural fluctuations present during gait in the stride length and step
      width time series are more regular and repeatable in patients with MS. These
      changes implied that patients with MS may exhibit reduced capacity to adapt and
      respond to perturbations during gait.

PMID- 22615328
TI  - 1Hz rTMS preconditioned by tDCS over the primary motor cortex in Parkinson's
      disease: absence of effect on arm lift and hand grip force control.
AB  - This study investigated whether a period of low frequency rTMS preconditioned by
      tDCS over the primary motor cortex modulates control of grip force in Parkinson's
      disease. The presented results are from the same patient cohort tested in an
      earlier study (Gruner et al. J Neural Transm 2010: 117: 207-216). 15 patients
      with Parkinson's disease (mean age: 69 +/- 8 years; average disease duration: 5
      +/- 3 years) on dopaminergic drugs performed a grasp-lift task with either hand
      before (baseline) and after a period of 1Hz rTMS (90% of the resting motor
      threshold; 900 pulses) preconditioned by sham, anodal or cathodal tDCS (1mA, 10
      min) over the primary motor cortex. We found that compared with baseline, none of
      the grip force parameters was significantly influenced by either stimulation
      session and concluded that grasping is a higher order motor skill, which cannot
      be modulated by tDCS preconditioned 1Hz rTMS in PD.

PMID- 22615329
TI  - Is the "low-hanging fruit" worth picking for antimicrobial stewardship programs?
AB  - A new antimicrobial stewardship program can be overwhelmed at the breadth of
      interventions and education required to conduct a successful program. The
      expression "low-hanging fruit," in reference to stewardship, refers to selecting
      the most obtainable targets rather than confronting more complicated management
      issues. These targets include intravenous-to-oral conversions, batching of
      intravenous antimicrobials, therapeutic substitutions, and formulary restriction.
      These strategies require fewer resources and less effort than other stewardship
      activities; however, they are applicable to a variety of healthcare settings,
      including limited-resource hospitals, and have demonstrated significant financial
      savings. Our stewardship program found that staged and systematic interventions
      that focus on obvious areas of need, that is, low hanging fruit, provided early
      successes in our expanded program with a substantial cumulative cost savings of
      $832,590.

PMID- 22615330
TI  - Food-borne origins of Escherichia coli causing extraintestinal infections.
AB  - Most human extraintestinal Escherichia coli infections, including those involving
      antimicrobial resistant strains, are caused by the members of a limited number of
      distinctive E. coli lineages, termed extraintestinal pathogenic E. coli (ExPEC),
      that have a special ability to cause disease at extraintestinal sites when they
      exit their usual reservoir in the host's intestinal tract. Multiple lines of
      evidence suggest that many of the ExPEC strains encountered in humans with
      urinary tract infection, sepsis, and other extraintestinal infections, especially
      the most extensively antimicrobial-resistant strains, may have a food animal
      source, and may be transmitted to humans via the food supply. This review
      summarizes the evidence that food-borne organisms are a significant cause of
      extraintestinal E. coli infections in humans.

PMID- 22615331
TI  - In vitro susceptibilities and molecular analysis of vancomycin-intermediate and
      vancomycin-resistant Staphylococcus aureus isolates.
AB  - BACKGROUND: There is increasing frequency of vancomycin-intermediate and 
      resistant Staphylococcus aureus (VISA and VRSA) isolates identified in clinical
      practice. There are limited reports evaluating susceptibility patterns and
      molecular characteristics of these strains. METHODS: Laboratory analysis was
      performed on 13 VRSA and 33 VISA isolates, including susceptibility testing by
      broth microdilution, detection of Panton-Valentine leukocidin (PVL) genes,
      arginine catabolic mobile element (ACME), and staphylococcal cassette chromosome
      mec typing using polymerase chain reaction. Strain typing using pulsed-field gel
      electrophoresis (PFGE) was performed on VRSA isolates. RESULTS: Telavancin,
      linezolid, tigecycline, and minocycline were active against >90% of VISA
      isolates, while >90% of VRSA isolates were susceptible to ceftaroline,
      daptomycin, linezolid, minocyline, tigecycline, rifampin, and
      trimethoprim/sulfamethoxazole. There were no VISA or VRSA isolates that carried
      PVL genes or ACME, and most strains (69.8%) were staphylococcal cassette
      chromosome mec type II. VRSA isolates were predominantly related to USA100
      (53.8%) and none were related to USA300 or USA400. CONCLUSIONS: A large number of
      available antimicrobial agents retain very good in vitro activity against VRSA
      and VISA isolates. The present isolates appear to be derived from healthcare
      associated strains based on the absence of features associated with community
      associated strains, and VRSA isolates are polyclonal by PFGE.

PMID- 22615332
TI  - Old drugs, new purpose: retooling existing drugs for optimized treatment of
      resistant tuberculosis.
AB  - Treatment of drug-resistant tuberculosis is hindered by the high toxicity and
      poor efficacy of second-line drugs. New compounds must be used together with
      existing drugs, yet clinical trials to optimize combinations of drugs for drug
      resistant tuberculosis are lacking. We conducted an extensive review of existing
      in vitro, animal, and clinical studies involving World Health Organization
      defined group 1, 2, and 4 drugs used in drug-resistant tuberculosis regimens to
      inform clinical trials and identify critical research questions. Results suggest
      that optimizing the dosing of pyrazinamide, the injectables, and isoniazid for
      drug-resistant tuberculosis is a high priority. Additional pharmacokinetic,
      pharmacodynamic, and toxicodynamic studies are needed for pyrazinamide and
      ethionamide. Clinical trials of the comparative efficacy and appropriate
      treatment duration of injectables are recommended. For isoniazid, rapid genotypic
      tests for Mycobacterium tuberculosis mutations should be nested in clinical
      trials. Further research focusing on optimization of dose and duration of drugs
      with activity against drug-resistant tuberculosis is paramount.

PMID- 22615333
TI  - Electrocardiographic characteristics of potential organ donors and associations
      with cardiac allograft use.
AB  - BACKGROUND: Current regulations require that all cardiac allograft offers for
      transplantation must include an interpreted 12-lead electrocardiogram (ECG).
      However, little is known about the expected ECG findings in potential organ
      donors or the clinical significance of any identified abnormalities in terms of
      cardiac allograft function and suitability for transplantation. METHODS AND
      RESULTS: A single experienced reviewer interpreted the first ECG obtained after
      brain stem herniation in 980 potential organ donors managed by the California
      Transplant Donor Network from 2002 to 2007. ECG abnormalities were summarized,
      and associations between specific ECG findings and cardiac allograft use for
      transplantation were studied. ECG abnormalities were present in 51% of all cases
      reviewed. The most common abnormalities included voltage criteria for left
      ventricular hypertrophy, prolongation of the corrected QT interval, and
      repolarization changes (ST/T wave abnormalities). Fifty-seven percent of
      potential cardiac allografts in this cohort were accepted for transplantation.
      Left ventricular hypertrophy on ECG was a strong predictor of allograft nonuse.
      No significant associations were seen among corrected QT interval prolongation,
      repolarization changes, and allograft use for transplantation after adjusting for
      donor clinical variables and echocardiographic findings. CONCLUSIONS: We have
      performed the first comprehensive study of ECG findings in potential donors for
      cardiac transplantation. Many of the common ECG abnormalities seen in organ
      donors may result from the heightened state of sympathetic activation that occurs
      after brain stem herniation and are not associated with allograft use for
      transplantation.

PMID- 22615340
TI  - Antiplatelet drug response status does not predict recurrent ischemic events in
      stable cardiovascular patients: results of the Antiplatelet Drug Resistances and
      Ischemic Events study.
AB  - BACKGROUND: The biological response to antiplatelet drugs has repeatedly been
      shown to predict the recurrence of major adverse cardiovascular events (MACEs).
      However, most studies involved coronary artery disease patients with recent
      vessel injury shortly after the initiation of antiplatelet therapy. Data on
      stable cardiovascular patients are scarce, and the added predictive value of
      specific assays (the vasodilator phosphoprotein assay for the clopidogrel
      response and serum thromboxane B2 for the aspirin response) and aggregation-based
      assays relative to common predictors has rarely been addressed. METHODS AND
      RESULTS: Stable cardiovascular outpatients participating in the Antiplatelet Drug
      Resistances and Ischemic Events (ADRIE) study (n=771) were tested twice, at 2
      separate visits, with specific and aggregation-based assays. Follow-up lasted 3
      years, and <1% of patients were lost to follow-up. MACEs were adjudicated by an
      independent committee. Multivariate survival analyses included relevant variables
      identified in univariate analysis and platelet function test results. The C-index
      was used to express the prognostic value of various multivariate models. MACEs,
      the primary end point, occurred in 16% of patients. Hypertension, smoking, older
      age, and elevated low-density lipoprotein cholesterol were predictive of MACE
      recurrence, with a C-index of 0.63 (P<0.001). Neither the specific nor the
      aggregation-based assays added significant predictive value for the primary end
      point. CONCLUSIONS: Biological antiplatelet drug responsiveness, measured with
      specific or aggregation-based assays, has no incremental predictive value over
      common cardiovascular risk factors for MACE recurrence in stable cardiovascular
      outpatients. These results do not support platelet function testing for MACE risk
      evaluation in stable cardiovascular patients. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00501423.

PMID- 22615341
TI  - Duration of QRS complex in resting electrocardiogram is a predictor of sudden
      cardiac death in men.
AB  - BACKGROUND: Previous studies indicate that increased QRS duration in ECG is
      related to the risk of all-cause death. However, the association of QRS duration
      with the risk of sudden cardiac death (SCD) is not well documented in large
      population-based studies. Our aim was to examine the relation of QRS duration
      with SCD in a population-based sample of men. METHODS AND RESULTS: This
      prospective study was based on a cohort of 2049 men aged 42 to 60 years at
      baseline with a 19-year follow-up, during which a total of 156 SCDs occurred. As
      a continuous variable, each 10-ms increase in QRS duration was associated with a
      27% higher risk for SCD (relative risk, 1.27; 95% confidence interval, 1.14-1.40;
      P<0.001). Subjects with QRS duration of >110 ms (highest quintile) had a 2.50
      fold risk for SCD (relative risk, 2.50; 95% confidence interval, 1.38-4.55;
      P=0.002) compared with those with QRS duration of <96 ms (lowest quintile), after
      adjustment for established key demographic and clinical risk factors (age,
      alcohol consumption, previous myocardial infarction, smoking, serum low- and high
      density lipoprotein cholesterol, C-reactive protein, type 2 diabetes mellitus,
      body mass index, systolic blood pressure, and cardiorespiratory fitness). In
      addition to QRS duration, smoking, previous myocardial infarction, type 2
      diabetes mellitus, cardiorespiratory fitness, body mass index, systolic blood
      pressure, and C-reactive protein were independently associated with the risk of
      SCD. CONCLUSIONS: QRS duration is an independent predictor of the risk of SCD and
      may have utility in estimating SCD risk in the general population.

PMID- 22615342
TI  - Immediate antioxidant and antiplatelet effect of atorvastatin via inhibition of
      Nox2.
AB  - BACKGROUND: Statins exert an antithrombotic effect in patients at risk of or with
      acute thrombosis, but no study has investigated whether this effect is immediate
      and whether there is an underline mechanism. METHODS AND RESULTS: Patients with
      hypercholesterolemia were randomly allocated to a Mediterranean diet with low
      cholesterol intake (<300 mg/d; n=15) or atorvastatin (40 mg/d; n=15). Oxidative
      stress, as assessed by serum Nox2 and urinary isoprostanes, and platelet
      activation, as assessed by platelet recruitment, platelet isoprostanes, and
      thromboxane A(2), platelet Nox2, Rac1, p47(phox), protein kinase C, vasodilator
      stimulated phosphoprotein, nitric oxide, and phospholipase A(2), were determined
      at baseline and after 2, 24, and 72 hours and 7 days of follow-up. An in vitro
      study was also performed to see whether atorvastatin affects platelet oxidative
      stress and activation. The atorvastatin-assigned group showed a significant and
      progressive reduction of urinary isoprostanes and serum Nox2, along with
      inhibition of platelet recruitment, platelet isoprostanes, Nox2, Rac1, p47(phox),
      and protein kinase C, starting 2 hours after administration. Platelet
      phospholipase A(2) and thromboxane A(2) significantly decreased and vasodilator
      stimulated phosphoprotein and nitric oxide increased after 24 hours. Low-density
      lipoprotein cholesterol decreased significantly after 72 hours and further
      declined after 7 days. No changes were observed in the Mediterranean diet group.
      In vitro experiments demonstrated that atorvastatin dose-dependently inhibited
      platelet Nox2 and phospholipase A(2) activation, along with inhibition of
      platelet recruitment, platelet isoprostanes, and thromboxane A(2), and increased
      vasodilator-stimulated phosphoprotein and nitric oxide. CONCLUSIONS: The study
      provides the first evidence that atorvastatin acutely and simultaneously
      decreases oxidative stress and platelet activation by directly inhibiting
      platelet Nox2 and ultimately platelet isoprostanes and thromboxane A(2). These
      findings provide a rationale for the use of statins to prevent or modulate
      coronary thrombosis. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01322711.

PMID- 22615343
TI  - The United States Registry for Fibromuscular Dysplasia: results in the first 447
      patients.
AB  - BACKGROUND: Fibromuscular dysplasia (FMD), a noninflammatory disease of medium
      size arteries, may lead to stenosis, occlusion, dissection, and/or aneurysm.
      There has been little progress in understanding the epidemiology, pathogenesis,
      and outcomes since its first description in 1938. METHODS AND RESULTS: Clinical
      features, presenting symptoms, and vascular events are reviewed for the first 447
      patients enrolled in a national FMD registry from 9 US sites. Vascular beds were
      imaged selectively based on clinical presentation and local practice. The
      majority of patients were female (91%) with a mean age at diagnosis of 51.9 (SD
      13.4 years; range, 5-83 years). Hypertension, headache, and pulsatile tinnitus
      were the most common presenting symptoms of the disease. Self-reported family
      history of stroke (53.5%), aneurysm (23.5%), and sudden death (19.8%) were
      common, but FMD in first- or second-degree relatives was reported only in 7.3%.
      FMD was identified in the renal artery in 294 patients, extracranial carotid
      arteries in 251 patients, and vertebral arteries in 82 patients. A past or
      presenting history of vascular events were common: 19.2% of patients had a
      transient ischemic attack or stroke, 19.7% had experienced arterial
      dissection(s), and 17% of patients had an aneurysm(s). The most frequent
      indications for therapy were hypertension, aneurysm, and dissection. CONCLUSIONS:
      In this registry, FMD occurred primarily in middle-aged women, although it
      presents across the lifespan. Cerebrovascular FMD occurred as frequently as renal
      FMD. Although a significant proportion of FMD patients may present with a serious
      vascular event, many present with nonspecific symptoms and a subsequent delay in
      diagnosis.

PMID- 22615344
TI  - Long-term outcome of aortic dissection with patent false lumen: predictive role
      of entry tear size and location.
AB  - BACKGROUND: Patent false lumen in aortic dissection has been associated with poor
      prognosis. We aimed to assess the natural evolution of this condition and
      predictive factors. METHODS AND RESULTS: One hundred eighty-four consecutive
      patients, 108 surgically treated type A and 76 medically treated type B, were
      discharged after an acute aortic dissection with patent false lumen.
      Transesophageal echocardiography was performed before discharge, and computed
      tomography was performed at 3 months and yearly thereafter. Median follow-up was
      6.42 years (quartile 1 to quartile 3: 3.31-10.49). Forty-nine patients died
      during follow-up (22 type A, 27 type B), 31 suddenly. Surgical or endovascular
      treatment was indicated in 10 type A and 25 type B cases. Survival free from
      sudden death and surgical-endovascular treatment was 0.90, 0.81, and 0.46 (95%
      CI, 0.36-0.55) at 3, 5, and 10 years, respectively. Multivariate analysis
      identified baseline maximum descending aorta diameter (hazard ratio [HR]: 1.32
      [1.10-1.59]; P=0.003), proximal location (HR: 1.84 [1.06-3.19]; P=0.03), and
      entry tear size (HR: 1.13 [1.08-1.2]; P<0.001) as predictors of dissection
      related adverse events, whereas mortality was predicted by baseline maximum
      descending aorta diameter (HR: 1.36 [1.08-1.70]; P=0.008), entry tear size (HR:
      1.1 [1.04-1.16]; P=0.001), and Marfan syndrome (HR: 3.66 [1.65-8.13]; P=0.001).
      CONCLUSIONS: Aortic dissection with persistent patent false lumen carries a high
      risk of complications. In addition to Marfan syndrome and aorta diameter, a large
      entry tear located in the proximal part of the dissection identifies a high-risk
      subgroup of patients who may benefit from earlier and more aggressive therapy.

PMID- 22615345
TI  - Trends in patients hospitalized with heart failure and preserved left ventricular
      ejection fraction: prevalence, therapies, and outcomes.
AB  - BACKGROUND: Heart failure with preserved ejection fraction (EF) is a common
      syndrome, but trends in treatments and outcomes are lacking. METHODS AND RESULTS:
      We analyzed data from 275 hospitals in Get With the Guidelines-Heart Failure from
      January 2005 to October 2010. Patients were stratified by EF as reduced EF (EF
      <40% [HF-reduced EF]), borderline EF (40%<=EF<50% [HF-borderline EF]), or
      preserved (EF >=50% [HF-preserved EF]). Using multivariable models, we examined
      trends in therapies and outcomes. Among 110 621 patients, 50% (55 083) had HF
      reduced EF, 14% (15 184) had HF-borderline EF, and 36% (40 354) had HF-preserved
      EF. From 2005 to 2010, the proportion of hospitalizations for HF-preserved EF
      increased from 33% to 39% (P<0.0001). In multivariable analyses, use of
      angiotensin-converting enzyme inhibitors/angiotensin receptor blockers at
      discharge decreased in all EF groups, and beta-blocker use increased. Patients
      with HF-preserved EF less frequently achieved blood pressure control (adjusted
      odds ratio, 0.44 versus HF-reduced EF; P<0.001) and were more likely discharged
      to skilled nursing (adjusted odds ratio, 1.16 versus HF-reduced EF; P<0.001). In
      hospital mortality for HF-preserved EF decreased from 3.32% in 2005 to 2.35% in
      2010 (adjusted odds ratio, 0.89 per year; P=0.01) but was stable for patients
      with HF-reduced EF (3.03%-2.83%; adjusted odds ratio, 0.93 per year; P=0.10).
      CONCLUSIONS: Hospitalization for HF-preserved EF is increasing relative to HF
      reduced EF. Although in-hospital mortality for patients with HF-preserved EF
      declined over the study period, an important opportunity remains for identifying
      evidence-based therapies in patients with HF-preserved EF.

PMID- 22615346
TI  - Identification and characterization of protein phosphatase 2C activation by
      ceramide.
AB  - Ceramide is a bioactive sphingolipid with many associated biological outcomes,
      yet there is a significant gap in our current understanding of how ceramide
      mediates these processes. Previously, ceramide has been shown to activate protein
      phosphatase (PP) 1 and 2A. While continuing this line of work, a late fraction
      from a Mono-Q column was consistently observed to be activated by ceramide, yet
      PP1 and PP2A were undetectable in this fraction. Proteomic analysis of this
      fraction revealed the identity of the phosphatase to be PP2Cgamma/PPM1G. This was
      consistent with our findings that PP2Cgamma 1-eluted in a high salt fraction due
      to its strongly acidic domain, and 2-was insensitive to okadaic acid. Further
      characterization was performed with PP2Calpha, which showed robust activation by
      C(6)-ceramide. Activation was specific for the erythro conformation of ceramide
      and the presence of the acyl chain and hydroxyl group at the first carbon. In
      order to demonstrate more physiological activation of PP2Calpha by ceramide,
      phospho-p38delta was utilized as substrate. Indeed, PP2Calpha induced the
      dephosphorylation of p38delta only in the presence of C(16)-ceramide. Taken
      together, these results show that the PP2C family of phosphatases is activated by
      ceramide, which may have important consequences in mediating the biological
      effects of ceramide.

PMID- 22615347
TI  - Evidence that publication bias contaminated studies relating social class and
      unethical behavior.

PMID- 22615348
TI  - Cellular mechanical properties reflect the differentiation potential of adipose
      derived mesenchymal stem cells.
AB  - The mechanical properties of adipose-derived stem cell (ASC) clones correlate
      with their ability to produce tissue-specific metabolites, a finding that has
      dramatic implications for cell-based regenerative therapies. Autologous ASCs are
      an attractive cell source due to their immunogenicity and multipotent
      characteristics. However, for practical applications ASCs must first be purified
      from other cell types, a critical step which has proven difficult using surface
      marker approaches. Alternative enrichment strategies identifying broad categories
      of tissue-specific cells are necessary for translational applications. One
      possibility developed in our lab uses single-cell mechanical properties as
      predictive biomarkers of ASC clonal differentiation capability. Elastic and
      viscoelastic properties of undifferentiated ASCs were tested via atomic force
      microscopy and correlated with lineage-specific metabolite production. Cell
      sorting simulations based on these "mechanical biomarkers" indicated they were
      predictive of differentiation capability and could be used to enrich for tissue
      specific cells, which if implemented could dramatically improve the quality of
      regenerated tissues.

PMID- 22615349
TI  - In vivo excitation of nanoparticles using luminescent bacteria.
AB  - The lux operon derived from Photorhabdus luminescens incorporated into bacterial
      genomes, elicits the production of biological chemiluminescence typically
      centered on 490 nm. The light-producing bacteria are widely used for in vivo
      bioluminescence imaging. However, in living samples, a common difficulty is the
      presence of blue-green absorbers such as hemoglobin. Here we report a
      characterization of fluorescence by unbound excitation from luminescence, a
      phenomenon that exploits radiating luminescence to excite nearby fluorophores by
      epifluorescence. We show that photons from bioluminescent bacteria radiate over
      mesoscopic distances and induce a red-shifted fluorescent emission from
      appropriate fluorophores in a manner distinct from bioluminescence resonance
      energy transfer. Our results characterizing fluorescence by unbound excitation
      from luminescence, both in vitro and in vivo, demonstrate how the resulting blue
      to-red wavelength shift is both necessary and sufficient to yield contrast
      enhancement revealing mesoscopic proximity of luminescent and fluorescent probes
      in the context of living biological tissues.

PMID- 22615350
TI  - Amorphous diamond-structured photonic crystal in the feather barbs of the scarlet
      macaw.
AB  - Noniridescent coloration by the spongy keratin in parrot feather barbs has
      fascinated scientists. Nonetheless, its ultimate origin remains as yet
      unanswered, and a quantitative structural and optical description is still
      lacking. Here we report on structural and optical characterizations and numerical
      simulations of the blue feather barbs of the scarlet macaw. We found that the
      sponge in the feather barbs is an amorphous diamond-structured photonic crystal
      with only short-range order. It possesses an isotropic photonic pseudogap that is
      ultimately responsible for the brilliant noniridescent coloration. We further
      unravel an ingenious structural optimization for attaining maximum coloration
      apparently resulting from natural evolution. Upon increasing the material
      refractive index above the level provided by nature, there is an interesting
      transition from a photonic pseudogap to a complete bandgap.

PMID- 22615351
TI  - Rewritable digital data storage in live cells via engineered control of
      recombination directionality.
AB  - The use of synthetic biological systems in research, healthcare, and
      manufacturing often requires autonomous history-dependent behavior and therefore
      some form of engineered biological memory. For example, the study or
      reprogramming of aging, cancer, or development would benefit from genetically
      encoded counters capable of recording up to several hundred cell division or
      differentiation events. Although genetic material itself provides a natural data
      storage medium, tools that allow researchers to reliably and reversibly write
      information to DNA in vivo are lacking. Here, we demonstrate a rewriteable
      recombinase addressable data (RAD) module that reliably stores digital
      information within a chromosome. RAD modules use serine integrase and excisionase
      functions adapted from bacteriophage to invert and restore specific DNA
      sequences. Our core RAD memory element is capable of passive information storage
      in the absence of heterologous gene expression for over 100 cell divisions and
      can be switched repeatedly without performance degradation, as is required to
      support combinatorial data storage. We also demonstrate how programmed
      stochasticity in RAD system performance arising from bidirectional recombination
      can be achieved and tuned by varying the synthesis and degradation rates of
      recombinase proteins. The serine recombinase functions used here do not require
      cell-specific cofactors and should be useful in extending computing and control
      methods to the study and engineering of many biological systems.

PMID- 22615352
TI  - Pulse-induced nonequilibrium dynamics of acetylene inside carbon nanotube studied
      by an ab initio approach.
AB  - Nanoscale molecular confinement substantially modifies the functionality and
      electronic properties of encapsulated molecules. Many works have approached this
      problem from the perspective of quantifying ground-state molecular changes, but
      little is known about the nonequilibrium dynamics of encapsulated molecular
      system. In this letter, we report an analysis of the nonequilibrium dynamics of
      acetylene (C(2)H(2)) inside a semiconducting carbon nanotube (CNT). An ultrashort
      high-intense laser pulse (2 fs width and 10(15) W/cm(2) intensity) brings the
      systems out of equilibrium. This process is modeled by comprehensive first
      principles time-dependent density-functional simulations. When encapsulated,
      acetylene dimer, unlike a single acetylene molecule, exhibits correlated
      vibrational dynamics (C-C bond rotation and H-C-C bending) that is markedly
      different from the dynamics observed in the gas phase. This result highlights the
      role of CNT in modulating the optical electric field within the tube. At longer
      simulation timescales (> 20 fs) in the largest-diameter tube studied here
      [CNT(14,0)], we observe synchronized rotation about the C-C axes in the dimer and
      ultimately ejection of one of the four hydrogen atoms. Our results illustrate the
      richness of photochemical phenomena in confined geometries.

PMID- 22615353
TI  - Nanoelectrodes for determination of reactive oxygen and nitrogen species inside
      murine macrophages.
AB  - Reactive oxygen and nitrogen species (ROS and RNS) produced by macrophages are
      essential for protecting a human body against bacteria and viruses. Micrometer
      sized electrodes coated with Pt black have previously been used for selective and
      sensitive detection of ROS and RNS in biological systems. To determine ROS and
      RNS inside macrophages, one needs smaller (i.e., nanometer-sized) sensors. In
      this article, the methodologies have been extended to the fabrication and
      characterization of Pt/Pt black nanoelectrodes. Electrodes with the metal surface
      flush with glass insulator, most suitable for quantitative voltammetric
      experiments, were fabricated by electrodeposition of Pt black inside an etched
      nanocavity under the atomic force microscope control. Despite a nanometer-scale
      radius, the true surface area of Pt electrodes was sufficiently large to yield
      stable and reproducible responses to ROS and RNS in vitro. The prepared
      nanoprobes were used to penetrate cells and detect ROS and RNS inside
      macrophages. Weak and very short leaks of ROS/RNS from the vacuoles into the
      cytoplasm were detected, which a macrophage is equipped to clean within a couple
      of seconds, while higher intensity oxidative bursts due to the emptying of
      vacuoles outside persist on the time scale of tens of seconds.

PMID- 22615354
TI  - Magnetic stripes and skyrmions with helicity reversals.
AB  - It was recently realized that topological spin textures do not merely have
      mathematical beauty but can also give rise to unique functionalities of magnetic
      materials. An example is the skyrmion--a nano-sized bundle of noncoplanar spins-
      that by virtue of its nontrivial topology acts as a flux of magnetic field on
      spin-polarized electrons. Lorentz transmission electron microscopy recently
      emerged as a powerful tool for direct visualization of skyrmions in
      noncentrosymmetric helimagnets. Topologically, skyrmions are equivalent to
      magnetic bubbles (cylindrical domains) in ferromagnetic thin films, which were
      extensively explored in the 1970s for data storage applications. In this study we
      use Lorentz microscopy to image magnetic domain patterns in the prototypical
      magnetic oxide-M-type hexaferrite with a hint of scandium. Surprisingly, we find
      that the magnetic bubbles and stripes in the hexaferrite have a much more complex
      structure than the skyrmions and spirals in helimagnets, which we associate with
      the new degree of freedom--helicity (or vector spin chirality) describing the
      direction of spin rotation across the domain walls. We observe numerous random
      reversals of helicity in the stripe domain state. Random helicity of cylindrical
      domain walls coexists with the positional order of magnetic bubbles in a
      triangular lattice. Most unexpectedly, we observe regular helicity reversals
      inside skyrmions with an unusual multiple-ring structure.

PMID- 22615355
TI  - Role of semiconductivity and ion transport in the electrical conduction of
      melanin.
AB  - Melanins are pigmentary macromolecules found throughout the biosphere that, in
      the 1970s, were discovered to conduct electricity and display bistable switching.
      Since then, it has been widely believed that melanins are naturally occurring
      amorphous organic semiconductors. Here, we report electrical conductivity, muon
      spin relaxation, and electron paramagnetic resonance measurements of melanin as
      the environmental humidity is varied. We show that hydration of melanin shifts
      the comproportionation equilibrium so as to dope electrons and protons into the
      system. This equilibrium defines the relative proportions of hydroxyquinone,
      semiquinone, and quinone species in the macromolecule. As such, the mechanism
      explains why melanin at neutral pH only conducts when "wet" and suggests that
      both carriers play a role in the conductivity. Understanding that melanin is an
      electronic-ionic hybrid conductor rather than an amorphous organic semiconductor
      opens exciting possibilities for bioelectronic applications such as ion-to
      electron transduction given its biocompatibility.

PMID- 22615356
TI  - Theoretical study of catalytic mechanism for single-site water oxidation process.
AB  - Water oxidation is a linchpin in solar fuels formation, and catalysis by single
      site ruthenium complexes has generated significant interest in this area.
      Combining several theoretical tools, we have studied the entire catalytic cycle
      of water oxidation for a single-site catalyst starting with
      [Ru(II)(tpy)(bpm)(OH(2))](2+) (i.e., [Ru(II)-OH(2)](2+); tpy is 2,2':6',2''
      terpyridine and bpm is 2,2'-bypyrimidine) as a representative example of a new
      class of single-site catalysts. The redox potentials and pK(a) calculations for
      the first two proton-coupled electron transfers (PCETs) from [Ru(II)-OH(2)](2+)
      to [Ru(IV) = O](2+) and the following electron-transfer process to [Ru(V) =
      O](3+) suggest that these processes can proceed readily in acidic or weakly basic
      conditions. The subsequent water splitting process involves two water molecules,
      [Ru(V) = O](3+) to generate [Ru(III)-OOH](2+), and H(3)O(+) with a low activation
      barrier (~10 kcal/mol). After the key O-O bond forming step in the single-site Ru
      catalysis, another PECT process oxidizes [Ru(III)-OOH](2+) to [Ru(IV)-OO](2+)
      when the pH is lower than 3.7. Two possible forms of [Ru(IV)-OO](2+), open and
      closed, can exist and interconvert with a low activation barrier (< 7 kcal/mol)
      due to strong spin-orbital coupling effects. In Pathway 1 at pH = 1.0, oxygen
      release is rate-limiting with an activation barrier ~12 kcal/mol while the
      electron-transfer step from [Ru(IV)-OO](2+) to [Ru(V)-OO](3+) becomes rate
      determining at pH = 0 (Pathway 2) with Ce(IV) as oxidant. The results of these
      theoretical studies with atomistic details have revealed subtle details of
      reaction mechanisms at several stages during the catalytic cycle. This
      understanding is helpful in the design of new catalysts for water oxidation.

PMID- 22615357
TI  - Nuclear export of single native mRNA molecules observed by light sheet
      fluorescence microscopy.
AB  - Nuclear export of mRNA is a key transport process in eukaryotic cells. To
      investigate it, we labeled native mRNP particles in living Chironomus tentans
      salivary gland cells with fluorescent hrp36, the hnRNP A1 homolog, and the
      nuclear envelope by fluorescent NTF2. Using light sheet microscopy, we traced
      single native mRNA particles across the nuclear envelope. The particles were
      observed to often probe nuclear pore complexes (NPC) at their nuclear face, and
      in only 25% of the cases yielded actual export. The complete export process took
      between 65 ms up to several seconds. A rate-limiting step was observed, which
      could be assigned to the nuclear basket of the pore and might correspond to a
      repositioning and unfolding of mRNPs before the actual translocation. Analysis of
      single fluorescent Dbp5 molecules, the RNA helicase essential for mRNA export,
      revealed that Dbp5 most often approached the cytoplasmic face of the NPC, and
      exhibited a binding duration of approximately 55 ms. Our results have allowed a
      refinement of the current models for mRNA export.

PMID- 22615358
TI  - Weak electron-phonon coupling contributing to high thermoelectric performance in
      n-type PbSe.
AB  - PbSe is a surprisingly good thermoelectric material due, in part, to its low
      thermal conductivity that had been overestimated in earlier measurements. The
      thermoelectric figure of merit, zT, can exceed 1 at high temperatures in both p
      type and n-type PbSe, similar to that found in PbTe. While the p-type lead
      chalcogenides (PbSe and PbTe) benefit from the high valley degeneracy (12 or more
      at high temperature) of the valence band, the n-type versions are limited to a
      valley degeneracy of 4 in the conduction band. Yet the n-type lead chalcogenides
      achieve a zT nearly as high as the p-type lead chalcogenides. This effect can be
      attributed to the weaker electron-phonon coupling (lower deformation potential
      coefficient) in the conduction band as compared with that in the valence band,
      which leads to higher mobility of electrons compared to that of holes. This study
      of PbSe illustrates the importance of the deformation potential coefficient of
      the charge-carrying band as one of several key parameters to consider for band
      structure engineering and the search for high performance thermoelectric
      materials.

PMID- 22615359
TI  - Direct chemical evidence for eumelanin pigment from the Jurassic period.
AB  - Melanin is a ubiquitous biological pigment found in bacteria, fungi, plants, and
      animals. It has a diverse range of ecological and biochemical functions,
      including display, evasion, photoprotection, detoxification, and metal
      scavenging. To date, evidence of melanin in fossil organisms has relied entirely
      on indirect morphological and chemical analyses. Here, we apply direct chemical
      techniques to categorically demonstrate the preservation of eumelanin in two >
      160 Ma Jurassic cephalopod ink sacs and to confirm its chemical similarity to the
      ink of the modern cephalopod, Sepia officinalis. Identification and
      characterization of degradation-resistant melanin may provide insights into its
      diverse roles in ancient organisms.

PMID- 22615360
TI  - Nascent RNA structure modulates the transcriptional dynamics of RNA polymerases.
AB  - RNA polymerase pausing represents an important mechanism of transcriptional
      regulation. In this study, we use a single-molecule transcription assay to
      investigate the effect of template base-pair composition on pausing by RNA
      polymerase II and the evolutionarily distinct mitochondrial polymerase Rpo41. For
      both enzymes, pauses are shorter and less frequent on GC-rich templates.
      Significantly, incubation with RNase abolishes the template dependence of
      pausing. A kinetic model, wherein the secondary structure of the nascent RNA
      poses an energetic barrier to pausing by impeding backtracking along the
      template, quantitatively predicts the pause densities and durations observed. The
      energy barriers extracted from the data correlate well with RNA folding energies
      obtained from cotranscriptional folding simulations. These results reveal that
      RNA secondary structures provide a cis-acting mechanism by which sequence
      modulates transcriptional elongation.

PMID- 22615361
TI  - Small anatomical variant has profound implications for evolution of human birth
      and brain development.

PMID- 22615362
TI  - Revised paradigm of aquatic biofilm formation facilitated by microgel transparent
      exopolymer particles.
AB  - Transparent exopolymer particles (TEPs) are planktonic, organic microgels that
      are ubiquitous in aqueous environments. Increasing evidence indicates that TEPs
      play an active role in the process of aquatic biofilm formation. Frequently, TEPs
      are intensely colonized by bacteria and other microorganisms, thus serving as hot
      spots of intense microbial activity. We introduce the term "protobiofilm" to
      refer to TEPs with extensive microbial outgrowth and colonization. Such particles
      display most of the characteristics of developing biofilm, with the exception of
      being attached to a surface. In this study, coastal seawater was passed through
      custom-designed flow cells that enabled direct observation of TEPs and
      protobiofilm in the feedwater stream by bright-field and epifluorescence
      microscopy. Additionally, we could follow biofilm development on immersed
      surfaces inside the flow cells. Within minutes, we observed TEP and protobiofilm
      patches adhering to these surfaces. By 30 min, confocal laser-scanning microscopy
      (CLSM) revealed numerous patches of Con A and SYTO 9 staining structures covering
      the surfaces. Atomic force microscopy showed details of a thin, highly sticky,
      organic conditioning layer between these patches. Bright-field and
      epifluorescence microscopy and CLSM showed that biofilm development (observed
      until 24 h) was profoundly inhibited in flow cells with seawater prefiltered to
      remove most large TEPs and protobiofilm. We propose a revised paradigm for
      aquatic biofilm development that emphasizes the critical role of microgel
      particles such as TEPs and protobiofilm in facilitating this process. Recognition
      of the role of planktonic microgels in aquatic biofilm formation can have applied
      importance for the water industry.

PMID- 22615363
TI  - Methylation of CenH3 arginine 37 regulates kinetochore integrity and chromosome
      segregation.
AB  - Centromeres of eukaryotic chromosomes mark the site for kinetochore formation and
      microtubule attachment and are essential for accurate chromosome segregation.
      Although centromere identity is defined by the presence of the histone H3 variant
      CenH3/centromere protein A (CENP-A), little is known about how epigenetic
      modifications on CenH3 might regulate kinetochore assembly and centromere
      function. Here we show that CENP-A from Saccharomyces cerevisiae, termed Cse4, is
      methylated on arginine 37 (R37) and that this methylation regulates the
      recruitment of kinetochore components to centromeric sequences. The absence of
      Cse4 R37 methylation caused a growth defect in cells lacking the centromere
      binding factor Cbf1 and synthetic lethality when combined with mutations in
      components of the Ctf19 linker complex that connects the inner kinetochore to
      microtubule-binding proteins. The cells showed a cell-cycle arrest in G2/M phase
      and defects in plasmid and chromosome segregation. Furthermore, the levels of
      Mtw1/MIND (Mtw1 including Nnf1-Nsl1-Dsn1) and Ctf19 components at the centromere,
      but not of Cse4 itself, were reduced in the absence of Cse4 R37 methylation, thus
      showing that this modification regulates the recruitment of linker components to
      the centromere. Altogether, our data identify a unique regulatory principle on
      centromeric chromatin by posttranslational modification of the amino terminus of
      CenH3.

PMID- 22615364
TI  - Global analysis of chaperone effects using a reconstituted cell-free translation
      system.
AB  - Protein folding is often hampered by protein aggregation, which can be prevented
      by a variety of chaperones in the cell. A dataset that evaluates which chaperones
      are effective for aggregation-prone proteins would provide an invaluable resource
      not only for understanding the roles of chaperones, but also for broader
      applications in protein science and engineering. Therefore, we comprehensively
      evaluated the effects of the major Escherichia coli chaperones, trigger factor,
      DnaK/DnaJ/GrpE, and GroEL/GroES, on ~800 aggregation-prone cytosolic E. coli
      proteins, using a reconstituted chaperone-free translation system. Statistical
      analyses revealed the robustness and the intriguing properties of chaperones. The
      DnaK and GroEL systems drastically increased the solubilities of hundreds of
      proteins with weak biases, whereas trigger factor had only a marginal effect on
      solubility. The combined addition of the chaperones was effective for a subset of
      proteins that were not rescued by any single chaperone system, supporting the
      synergistic effect of these chaperones. The resource, which is accessible via a
      public database, can be used to investigate the properties of proteins of
      interest in terms of their solubilities and chaperone effects.

PMID- 22615365
TI  - Heat shock factor-1 knockout induces multidrug resistance gene, MDR1b, and
      enhances P-glycoprotein (ABCB1)-based drug extrusion in the heart.
AB  - Heat-shock factor 1 (HSF-1), a transcription factor for heat-shock proteins
      (HSPs), is known to interfere with the transcriptional activity of many oncogenic
      factors. In the present work, we have discovered that HSF-1 ablation induced the
      multidrug resistance gene, MDR1b, in the heart and increased the expression of P
      glycoprotein (P-gp, ABCB1), an ATP binding cassette that is usually associated
      with multidrug-resistant cancer cells. The increase in P-gp enhanced the
      extrusion of doxorubicin (Dox) to alleviate Dox-induced heart failure and reduce
      mortality in mice. Dox-induced left ventricular (LV) dysfunction was
      significantly reduced in HSF-1(-/-) mice. DNA-binding activity of NF-kappaB was
      higher in HSF-1(-/-) mice. IkappaB, the NF-kappaB inhibitor, was depleted due to
      enhanced IkappaB kinase (IKK)-alpha activity. In parallel, MDR1b gene expression
      and a large increase in P-gp and lowering Dox loading were observed in HSF-1(-/-)
      mouse hearts. Moreover, application of the P-gp antagonist, verapamil, increased
      Dox loading in HSF-1(-/-) cardiomyocytes, deteriorated cardiac function in HSF-1(
      /-) mice, and decreased survival. MDR1 promoter activity was higher in HSF-1(-/-)
      cardiomyocytes, whereas a mutant MDR1 promoter with heat-shock element (HSE)
      mutation showed increased activity only in HSF-1(+/+) cardiomyocytes. However,
      deletion of HSE and NF-kappaB binding sites diminished luminescence in both HSF
      1(+/+) and HSF-1(-/-) cardiomyocytes, suggesting that HSF-1 inhibits MDR1
      activity in the heart. Thus, because high levels of HSF-1 are attributed to poor
      prognosis of cancer, systemic down-regulation of HSF-1 before chemotherapy is a
      potential therapeutic approach to ameliorate the chemotherapy-induced
      cardiotoxicity and enhance cancer prognosis.

PMID- 22615366
TI  - Rethinking dog domestication by integrating genetics, archeology, and
      biogeography.
AB  - The dog was the first domesticated animal but it remains uncertain when the
      domestication process began and whether it occurred just once or multiple times
      across the Northern Hemisphere. To ascertain the value of modern genetic data to
      elucidate the origins of dog domestication, we analyzed 49,024 autosomal SNPs in
      1,375 dogs (representing 35 breeds) and 19 wolves. After combining our data with
      previously published data, we contrasted the genetic signatures of 121 breeds
      with a worldwide archeological assessment of the earliest dog remains.
      Correlating the earliest archeological dogs with the geographic locations of 14
      so-called "ancient" breeds (defined by their genetic differentiation) resulted in
      a counterintuitive pattern. First, none of the ancient breeds derive from regions
      where the oldest archeological remains have been found. Second, three of the
      ancient breeds (Basenjis, Dingoes, and New Guinea Singing Dogs) come from regions
      outside the natural range of Canis lupus (the dog's wild ancestor) and where dogs
      were introduced more than 10,000 y after domestication. These results demonstrate
      that the unifying characteristic among all genetically distinct so-called ancient
      breeds is a lack of recent admixture with other breeds likely facilitated by
      geographic and cultural isolation. Furthermore, these genetically distinct
      ancient breeds only appear so because of their relative isolation, suggesting
      that studies of modern breeds have yet to shed light on dog origins. We conclude
      by assessing the limitations of past studies and how next-generation sequencing
      of modern and ancient individuals may unravel the history of dog domestication.

PMID- 22615368
TI  - Packaging of influenza virus genome: robustness of selection.

PMID- 22615367
TI  - Pandemic H1N1 influenza vaccine induces a recall response in humans that favors
      broadly cross-reactive memory B cells.
AB  - We have previously shown that broadly neutralizing antibodies reactive to the
      conserved stem region of the influenza virus hemagglutinin (HA) were generated in
      people infected with the 2009 pandemic H1N1 strain. Such antibodies are rarely
      seen in humans following infection or vaccination with seasonal influenza virus
      strains. However, the important question remained whether the inactivated 2009
      pandemic H1N1 vaccine, like the infection, could also induce these broadly
      neutralizing antibodies. To address this question, we analyzed B-cell responses
      in 24 healthy adults immunized with the pandemic vaccine in 2009. In all cases,
      we found a rapid, predominantly IgG-producing vaccine-specific plasmablast
      response. Strikingly, the majority (25 of 28) of HA-specific monoclonal
      antibodies generated from the vaccine-specific plasmablasts neutralized more than
      one influenza strain and exhibited high levels of somatic hypermutation,
      suggesting they were derived from recall of B-cell memory. Indeed, memory B cells
      that recognized the 2009 pandemic H1N1 HA were detectable before vaccination not
      only in this cohort but also in samples obtained before the emergence of the
      pandemic strain. Three antibodies demonstrated extremely broad cross-reactivity
      and were found to bind the HA stem. Furthermore, one stem-reactive antibody
      recognized not only H1 and H5, but also H3 influenza viruses. This exceptional
      cross-reactivity indicates that antibodies capable of neutralizing most influenza
      subtypes might indeed be elicited by vaccination. The challenge now is to improve
      upon this result and design influenza vaccines that can elicit these broadly
      cross-reactive antibodies at sufficiently high levels to provide heterosubtypic
      protection.

PMID- 22615369
TI  - Symbionts provide pesticide detoxification.

PMID- 22615370
TI  - Dual functions of adaptor protein, phosphotyrosine interaction, PH domain and
      leucine zipper containing 1 (APPL1) in insulin signaling and insulin secretion.

PMID- 22615371
TI  - Parasite diversity and coinfection determine pathogen infection success and host
      fitness.
AB  - While the importance of changes in host biodiversity for disease risk continues
      to gain empirical support, the influence of natural variation in parasite
      diversity on epidemiological outcomes remains largely overlooked. Here, we
      combined field infection data from 2,191 amphibian hosts representing 158
      parasite assemblages with mechanistic experiments to evaluate the influence of
      parasite richness on both parasite transmission and host fitness. Using a guild
      of larval trematode parasites (six species) and an amphibian host, our
      experiments contrasted the effects of parasite richness vs. composition, observed
      vs. randomized assemblages, and additive vs. replacement designs. Consistent with
      the dilution effect hypothesis extended to intrahost diversity, increases in
      parasite richness reduced overall infection success, including infections by the
      most virulent parasite. However, the effects of parasite richness on host growth
      and survival were context dependent; pathology increased when parasites were
      administered additively, even when the presence of the most pathogenic species
      was held constant, but decreased when added species replaced or reduced virulent
      species, emphasizing the importance of community composition and assembly. These
      results were similar or stronger when community structures were weighted by their
      observed frequencies in nature. The field data also revealed the highly nested
      structure of parasite assemblages, with virulent species generally occupying
      basal positions, suggesting that increases in parasite richness and antagonism in
      nature will decrease virulent infections. Our findings emphasize the importance
      of parasite biodiversity and coinfection in affecting epidemiological responses
      and highlight the value of integrating research on biodiversity and community
      ecology for understanding infectious diseases.

PMID- 22615372
TI  - Structural differences between apoE3 and apoE4 may be useful in developing
      therapeutic agents for Alzheimer's disease.
AB  - Apolipoproteins E3 and E4, proteins with a molecular mass of 34.15 kDa, differ by
      a single amino acid change. ApoE4 contains an arginine residue at position 112,
      whereas apoE3 has a cysteine at this position. ApoE4 is the major risk factor for
      late-onset Alzheimer's disease, whereas apoE3, the common isoform, is neutral
      with respect to this disease. Here, using literature data from both hydrogen
      deuterium exchange and site-directed mutations, we suggest structural differences
      between these two isoforms that are distant from the site of the arginine-to
      cysteine change. These structural differences involve sequences from both the N-
      and C-terminal domains, sequentially far apart but structurally close. In
      addition, these regions are close to regions that bind lipid and to a region
      involved in association of apoE monomers to higher molecular weight forms. We
      discuss the possibility that these regions could be targeted preferentially to
      affect the function of apoE4 relative to apoE3.

PMID- 22615373
TI  - Intracerebral chondroitinase ABC and heparan sulfate proteoglycan glypican
      improve outcome from chronic stroke in rats.
AB  - Physical and chemical constraints imposed by the periinfarct glial scar may
      contribute to the limited clinical improvement often observed after ischemic
      brain injury. To investigate the role of some of these mediators in outcome from
      cerebral ischemia, we treated rats with the growth-inhibitory chondroitin sulfate
      proteoglycan neurocan, the growth-stimulating heparan sulfate proteoglycan
      glypican, or the chondroitin sulfate proteoglycan-degrading enzyme chondroitinase
      ABC. Neurocan, glypican, or chondroitinase ABC was infused directly into the
      infarct cavity for 7 d, beginning 7 d after middle cerebral artery occlusion.
      Glypican and chondroitinase ABC reduced glial fibrillary acidic protein
      immunoreactivity and increased microtubule-associated protein-2 immunoreactivity
      in the periinfarct region, and glypican- and chondroitinase ABC-treated rats
      showed behavioral improvement compared with neurocan- or saline-treated rats.
      Glypican and chondroitinase ABC also increased neurite extension in cortical
      neuron cultures. Glypican increased fibroblast growth factor-2 expression and
      chondroitinase ABC increased brain-derived neurotrophic factor expression in
      these cultures, whereas no such effects were seen following neurocan treatment.
      Thus, treatment with glypican or enzymatic disruption of neurocan with
      chondroitinase ABC improves gross anatomical, histological, and functional
      outcome in the chronic phase of experimental stroke in rats. Changes in growth
      factor expression and neuritogenesis may help to mediate these effects.

PMID- 22615375
TI  - Iterated Prisoner's Dilemma contains strategies that dominate any evolutionary
      opponent.
AB  - The two-player Iterated Prisoner's Dilemma game is a model for both sentient and
      evolutionary behaviors, especially including the emergence of cooperation. It is
      generally assumed that there exists no simple ultimatum strategy whereby one
      player can enforce a unilateral claim to an unfair share of rewards. Here, we
      show that such strategies unexpectedly do exist. In particular, a player X who is
      witting of these strategies can (i) deterministically set her opponent Y's score,
      independently of his strategy or response, or (ii) enforce an extortionate linear
      relation between her and his scores. Against such a player, an evolutionary
      player's best response is to accede to the extortion. Only a player with a theory
      of mind about his opponent can do better, in which case Iterated Prisoner's
      Dilemma is an Ultimatum Game.

PMID- 22615374
TI  - Epigenetic transgenerational inheritance of altered stress responses.
AB  - Ancestral environmental exposures have previously been shown to promote
      epigenetic transgenerational inheritance and influence all aspects of an
      individual's life history. In addition, proximate life events such as chronic
      stress have documented effects on the development of physiological, neural, and
      behavioral phenotypes in adulthood. We used a systems biology approach to
      investigate in male rats the interaction of the ancestral modifications carried
      transgenerationally in the germ line and the proximate modifications involving
      chronic restraint stress during adolescence. We find that a single exposure to a
      common-use fungicide (vinclozolin) three generations removed alters the
      physiology, behavior, metabolic activity, and transcriptome in discrete brain
      nuclei in descendant males, causing them to respond differently to chronic
      restraint stress. This alteration of baseline brain development promotes a change
      in neural genomic activity that correlates with changes in physiology and
      behavior, revealing the interaction of genetics, environment, and epigenetic
      transgenerational inheritance in the shaping of the adult phenotype. This is an
      important demonstration in an animal that ancestral exposure to an environmental
      compound modifies how descendants of these progenitor individuals perceive and
      respond to a stress challenge experienced during their own life history.

PMID- 22615376
TI  - Quantitative model for predicting lymph formation and muscle compressibility in
      skeletal muscle during contraction and stretch.
AB  - Skeletal muscle is widely perceived as nearly incompressible despite the fact
      that blood and lymphatic vessels within the endomysial and perimysial spaces
      undergo significant changes in diameter and length during stretch and
      contraction. These fluid shifts between fascicle and interstitial compartments
      have proved extremely difficult to measure. In this paper, we propose a
      theoretical framework based on a space-filling hexagonal fascicle array to
      provide predictions of the displacement of blood and lymph into and out of the
      muscle's endomysium and perimysium during stretch and contraction. We also use
      this model to quantify the distribution of blood and initial lymphatic (IL)
      vessels within a fascicle and its perimysial space using data for the rat
      spinotrapezius muscle. On average, there are 11 muscle fibers, 0.4
      arteriole/venule pairs, and 0.2 IL vessels per fascicle. The model predicts that
      the blood volume in the endomysial space increases 24% and decreases 22% for a
      20% contraction and stretch, respectively. However, these significant changes in
      blood volume in the endomysium produce a change of only ~2% in fascicle cross
      sectional area. In contrast, the entire muscle deviates from isovolumetry by 7%
      and 6% for a 20% contraction and stretch, respectively, largely attributable to
      the significantly larger blood volume changes that occur in the perimysial space.
      This suggests that arcade blood vessels in the perimysial space provide the
      primary pumping action required for the filling and emptying of ILs during
      muscular contraction and stretch.

PMID- 22615377
TI  - Cell type-specific targeting dissociates the therapeutic from the adverse effects
      of protein kinase inhibition in allergic skin disease.
AB  - The kinase p38alpha, originally identified because of its endotoxin- and cytokine
      inducible activity and affinity for antiinflammatory compounds, has been posited
      as a promising therapeutic target for various immune-mediated disorders. In
      clinical trials, however, p38alpha inhibitors produced adverse skin reactions and
      other toxic effects that often outweighed their benefits. Such toxicity may arise
      from a perturbation of physiological functions unrelated to or even protective
      against the disease being treated. Here, we show that the effect of interfering
      with p38alpha signaling can be therapeutic or adverse depending on the targeted
      cell type. Using a panel of mutant mice devoid of p38alpha in distinct cell types
      and an experimental model of allergic skin disease, we find that dendritic cell
      (DC)-intrinsic p38alpha function is crucial for both antigen-specific T-cell
      priming and T-cell-mediated skin inflammation, two independent processes
      essential for the immunopathogenesis. By contrast, p38alpha in other cell types
      serves to prevent excessive inflammation or maintain naive T-cell pools in the
      peripheral lymphoid tissues. These findings highlight a dilemma in the clinical
      use of p38alpha inhibitors, yet also suggest cell-selective targeting as a
      potential solution for improving their therapeutic index.

PMID- 22615378
TI  - Stress-induced epigenetic regulation of kappa-opioid receptor gene involves
      transcription factor c-Myc.
AB  - Exposure to stress is associated with adverse emotional and behavioral responses.
      Whereas the kappa-opioid receptor (KOR) system is known to mediate some of the
      effects, it is unclear whether and how stress affects epigenetic regulation of
      this gene. Because the KOR gene can use two promoters (Pr1 and Pr2) and two
      polyadenylation signals (PA1 and PA2), it is also interesting whether and how
      these distinct regulatory mechanisms are differentially modulated by stress. The
      current study examined the effects of stress on these different regulatory
      mechanisms of the KOR gene. Results showed that stress selectively increased the
      expression of KOR mRNA isoforms controlled by Pr1 and terminated at PA1 in
      specific brain areas including the medial-prefrontal cortex, hippocampus,
      brainstem, and sensorimotor cortex, but not in the amygdala or hypothalamus.
      These effects correlated with altered epigenetic state of KOR Pr1 chromatin, as
      well as elevation and increased recruitment of the principal transcription factor
      c-Myc, which could activate Pr1. Stress-induced modulation of Pr1 was further
      validated using glutamate-sensitive murine hippocampal cell line, HT22. The
      results revealed a common molecular mechanism underlying the effect of stress on
      selected chromatin regions of this gene at the cellular level and in the context
      of whole animal and identified a critical role for c-Myc in stress-triggered
      epigenetic regulation of the KOR gene locus. This study sheds light on the
      mechanisms of stress-induced epigenetic regulation that targets specific
      chromatin segments and suggests certain KOR transcripts and its principal
      transcription factor c-Myc as potential targets for brain-area-specific
      intervention.

PMID- 22615379
TI  - Structural basis for substrate specificity and catalysis of human histone
      acetyltransferase 1.
AB  - Histone acetyltransferase 1 is the founding member of the histone
      acetyltransferase superfamily and catalyzes lysine acetylation of newly
      synthesized histone H4. Here we report a 1.9-A resolution crystal structure of
      human histone acetyltransferase 1 in complex with acetyl coenzyme A and histone
      H4 peptide. The crystal structure reveals that the cofactor and the side chain of
      lysine 12 of histone H4 peptide are placed in the canyon between the central and
      C-terminal domains. Histone H4 peptide adopts a well-defined conformation and
      establishes an extensive set of interactions with the enzyme including invariant
      residues Glu64 and Trp199, which together govern substrate-binding specificity of
      histone acetyltransferase 1. Our structure-guided enzyme kinetic study further
      demonstrates a cumulative effect of the active-site residues Glu187, Glu276, and
      Asp277 on deprotonation of the epsilon-amino group of reactive Lys12 for direct
      attack of the acetyl group of the cofactor.

PMID- 22615381
TI  - Frequent skipped spawning in the world's largest cod population.
AB  - Life-history theory suggests that animals may skip reproductive events after
      initial maturation to maximize lifetime fitness. In iteroparous teleosts,
      verifying past spawning history is particularly difficult; the degree of skipped
      spawning at the population level therefore remains unknown. We unequivocally show
      frequent skipped spawning in Northeast Arctic cod (NEAC) in a massive field and
      laboratory effort from 2006 to 2008. This was verified by postovulatory follicles
      in temporarily arrested ovaries close to the putative spawning period. At the
      population level, "skippers" were estimated to be approximately equally abundant
      as spawning females in 2008, constituting ~24% of the females 60-100 cm. These
      females never truly started vitellogenesis and principally remained on the
      feeding grounds when spawners migrated southward, avoiding any migration costs.
      The proximate cause of skipping seems to be insufficient energy to initiate
      oocyte development, indicating that skipped spawning may partly be a density
      dependent response important in population regulation. Our data also indicate
      more skipping among smaller females and potential tradeoffs between current and
      future reproductive effort. We propose that skipped spawning is an integral life
      history component for NEAC, likely varying annually, and it could therefore be an
      underlying factor causing some of the currently unexplained large NEAC
      recruitment variation. The same may hold for other teleosts.

PMID- 22615380
TI  - CCAAT/enhancer-binding protein delta facilitates bacterial dissemination during
      pneumococcal pneumonia in a platelet-activating factor receptor-dependent manner.
AB  - CCAAT/enhancer-binding protein delta (C/EBPdelta) recently emerged as an
      essential player in the inflammatory response to bacterial infections. C/EBPdelta
      levels increase rapidly after a proinflammatory stimulus, and increasing
      C/EBPdelta levels seem to be indispensable for amplification of the inflammatory
      response. Here we aimed to elucidate the role of C/EBPdelta in host defense in
      community-acquired pneumococcal pneumonia. We show that C/EBPdelta(-/-) mice are
      relatively resistant to pneumococcal pneumonia, as indicated by delayed and
      reduced mortality, diminished outgrowth of pneumococci in lungs, and reduced
      dissemination of the infection. Moreover, expression of platelet-activating
      factor receptor (PAFR), which is known to potentiate bacterial translocation of
      gram-positive bacteria, was significantly reduced during infection in C/EBPdelta(
      /-) mice compared with WT controls. Importantly, cell stimulation experiments
      revealed that C/EBPdelta potentiates PAFR expression induced by lipoteichoic acid
      and pneumococci. Thus, C/EBPdelta exaggerates bacterial dissemination during
      Streptococcus pneumoniae-induced pulmonary infection, suggesting an important
      role for PAFR-dependent bacterial translocation.

PMID- 22615382
TI  - H3K4 demethylation by Jarid1a and Jarid1b contributes to retinoblastoma-mediated
      gene silencing during cellular senescence.
AB  - Cellular senescence is a tumor-suppressive program that involves chromatin
      reorganization and specific changes in gene expression that trigger an
      irreversible cell-cycle arrest. Here we combine quantitative mass spectrometry,
      ChIP deep-sequencing, and functional studies to determine the role of histone
      modifications on chromatin structure and gene-expression alterations associated
      with senescence in primary human cells. We uncover distinct senescence-associated
      changes in histone-modification patterns consistent with a repressive chromatin
      environment and link the establishment of one of these patterns--loss of H3K4
      methylation--to the retinoblastoma tumor suppressor and the H3K4 demethylases
      Jarid1a and Jarid1b. Our results show that Jarid1a/b-mediated H3K4 demethylation
      contributes to silencing of retinoblastoma target genes in senescent cells,
      suggesting a mechanism by which retinoblastoma triggers gene silencing.
      Therefore, we link the Jarid1a and Jarid1b demethylases to a tumor-suppressor
      network controlling cellular senescence.

PMID- 22615383
TI  - Oncogene-mediated alterations in chromatin conformation.
AB  - Emerging evidence suggests that chromatin adopts a nonrandom 3D topology and that
      the organization of genes into structural hubs and domains affects their
      transcriptional status. How chromatin conformation changes in diseases such as
      cancer is poorly understood. Moreover, how oncogenic transcription factors, which
      bind to thousands of sites across the genome, influence gene regulation by
      globally altering the topology of chromatin requires further investigation. To
      address these questions, we performed unbiased high-resolution mapping of intra-
      and interchromosome interactions upon overexpression of ERG, an oncogenic
      transcription factor frequently overexpressed in prostate cancer as a result of a
      gene fusion. By integrating data from genome-wide chromosome conformation capture
      (Hi-C), ERG binding, and gene expression, we demonstrate that oncogenic
      transcription factor overexpression is associated with global, reproducible, and
      functionally coherent changes in chromatin organization. The results presented
      here have broader implications, as genomic alterations in other cancer types
      frequently give rise to aberrant transcription factor expression, e.g., EWS-FLI1,
      c-Myc, n-Myc, and PML-RARalpha.

PMID- 22615384
TI  - Contribution of cryoelectron microscopy of vitreous sections to the understanding
      of biological membrane structure.
AB  - Using cryoelectron microscopy of vitreous sections, we investigated in situ the
      ultrastructure of biological membranes, selected from several cell types for
      their diverse biological functions. Here we describe how to visualize the two
      membrane leaflets and tightly apposed membranes, lying as close as 1.1 nm apart,
      by tuning the imaging conditions. We show how defects in membrane stacks may be
      clues to resolving their structure. Details of membrane proteins are also
      resolved, as well as protein lattices with correlations between stacked
      membranes. Imaging the cell in its native hydrated state can now be done in the
      nanometer resolution range, which should open unique routes for investigating
      structure-function relationships.

PMID- 22615385
TI  - Intron-mediated alternative splicing of Arabidopsis P5CS1 and its association
      with natural variation in proline and climate adaptation.
AB  - Drought-induced proline accumulation is widely observed in plants but its
      regulation and adaptive value are not as well understood. Proline accumulation of
      the Arabidopsis accession Shakdara (Sha) was threefold less than that of
      Landsberg erecta (Ler) and quantitative trait loci mapping identified a reduced
      function allele of the proline synthesis enzyme Delta(1)-pyrroline-5-carboxylate
      synthetase1 (P5CS1) as a basis for the lower proline of Sha. Sha P5CS1 had
      additional TA repeats in intron 2 and a G-to-T transversion in intron 3 that were
      sufficient to promote alternative splicing and production of a nonfunctional
      transcript lacking exon 3 (exon 3-skip P5CS1). In Sha, and additional accessions
      with the same intron polymorphisms, the nonfunctional exon 3-skip P5CS1 splice
      variant constituted as much as half of the total P5CS1 transcript. In a larger
      panel of Arabidopsis accessions, low water potential-induced proline accumulation
      varied by 10-fold and variable production of exon 3-skip P5CS1 among accessions
      was an important, but not the sole, factor underlying variation in proline
      accumulation. Population genetic analyses suggest that P5CS1 may have evolved
      under positive selection, and more extensive correlation of exon 3-skip P5CS1
      production than proline abundance with climate conditions of natural accessions
      also suggest a role of P5CS1 in local adaptation to the environment. These data
      identify a unique source of alternative splicing in plants, demonstrate a role of
      exon 3-skip P5CS1 in natural variation of proline metabolism, and suggest an
      association of P5CS1 and its alternative splicing with environmental adaptation.

PMID- 22615386
TI  - CTCF and cohesin help neurons raise their self-awareness.

PMID- 22615387
TI  - Predominance of heavily calcified coccolithophores at low CaCO3 saturation during
      winter in the Bay of Biscay.
AB  - Coccolithophores are an important component of the Earth system, and, as
      calcifiers, their possible susceptibility to ocean acidification is of major
      concern. Laboratory studies at enhanced pCO(2) levels have produced divergent
      results without overall consensus. However, it has been predicted from these
      studies that, although calcification may not be depressed in all species,
      acidification will produce "a transition in dominance from more to less heavily
      calcified coccolithophores" [Ridgwell A, et al., (2009) Biogeosciences 6:2611
      2623]. A recent observational study [Beaufort L, et al., (2011) Nature 476:80-83]
      also suggested that coccolithophores are less calcified in more acidic
      conditions. We present the results of a large observational study of
      coccolithophore morphology in the Bay of Biscay. Samples were collected once a
      month for over a year, along a 1,000-km-long transect. Our data clearly show that
      there is a pronounced seasonality in the morphotypes of Emiliania huxleyi, the
      most abundant coccolithophore species. Whereas pH and CaCO(3) saturation are
      lowest in winter, the E. huxleyi population shifts from <10% (summer) to >90%
      (winter) of the heavily calcified form. However, it is unlikely that the shifts
      in carbonate chemistry alone caused the morphotype shift. Our finding that the
      most heavily calcified morphotype dominates when conditions are most acidic is
      contrary to the earlier predictions and raises further questions about the fate
      of coccolithophores in a high-CO(2) world.

PMID- 22615388
TI  - Surgical removal of the parametrial fat pads stimulates apoptosis and inhibits
      UVB-induced carcinogenesis in mice fed a high-fat diet.
AB  - Removal of the parametrial fat pads (partial lipectomy) from female SKH-1 mice
      fed a high-fat diet inhibited UVB-induced carcinogenesis, but this was not
      observed in mice fed a low-fat chow diet. Partial lipectomy in high-fat-fed mice
      decreased the number of keratoacanthomas and squamous cell carcinomas per mouse
      by 76 and 79%, respectively, compared with sham-operated control mice irradiated
      with UVB for 33 wk. Immunohistochemical analysis indicated that partial lipectomy
      increased caspase 3 (active form) positive cells by 48% in precancerous epidermis
      away from tumors, by 68% in keratoacanthomas, and by 224% in squamous cell
      carcinomas compared with sham-operated control mice. In addition, partial
      lipectomy decreased cell proliferation away from tumors and in tumors. RT-PCR
      analysis for adipokines revealed that mRNAs for TIMP1, MCP1, and SerpinE1
      (proinflammatory/antiapoptotic cytokines) in the parametrial fat pads of sham
      operated control mice were 54- to 83-fold higher than levels in compensatory fat
      that returned after surgery in partially lipectomized mice at the end of the
      tumor study. Feeding mice high-fat diets for 2 wk increased levels of TIMP1 and
      other adipokines in serum and epidermis, and these increases were inhibited by
      removal of the parametrial fat pads. Our results are a unique demonstration that
      surgical removal of a specific tissue fat results in inhibition of carcinogenesis
      in obese mice. This inhibition was associated with an increase in apoptosis and a
      decrease in proliferation in tumors and in precancerous areas away from tumors.

PMID- 22615389
TI  - Social status predicts wound healing in wild baboons.
AB  - Social status can have striking effects on health in humans and other animals,
      but the causes often are unknown. In male vertebrates, status-related differences
      in health may be influenced by correlates of male social status that suppress
      immune responses. Immunosuppressive correlates of low social status may include
      chronic social stress, poor physical condition, and old age; the
      immunosuppressive correlates of high status may include high testosterone and
      energetic costs of reproduction. Here we test whether these correlates could
      create status-related differences in immune function by measuring the incidence
      of illness and injury and then examining healing rates in a 27-y data set of
      natural injuries and illnesses in wild baboon males. We found no evidence that
      the high testosterone and intense reproductive effort associated with high rank
      suppress immune responses. Instead, high-ranking males were less likely to become
      ill, and they recovered more quickly than low-ranking males, even controlling for
      differences in age. Notably, alpha males, who experience high glucocorticoids, as
      well as the highest testosterone and reproductive effort, healed significantly
      faster than other males, even other high-ranking males. We discuss why alpha
      males seem to escape from the immunosuppressive costs of glucocorticoids but low
      ranking males do not, including the idea that glucocorticoids' effects depend on
      an individual's physiological and social context.

PMID- 22615390
TI  - Full-length axon regeneration in the adult mouse optic nerve and partial recovery
      of simple visual behaviors.
AB  - The mature optic nerve cannot regenerate when injured, leaving victims of
      traumatic nerve damage or diseases such as glaucoma with irreversible visual
      losses. Recent studies have identified ways to stimulate retinal ganglion cells
      to regenerate axons part-way through the optic nerve, but it remains unknown
      whether mature axons can reenter the brain, navigate to appropriate target areas,
      or restore vision. We show here that with adequate stimulation, retinal ganglion
      cells are able to regenerate axons the full length of the visual pathway and on
      into the lateral geniculate nucleus, superior colliculus, and other visual
      centers. Regeneration partially restores the optomotor response, depth
      perception, and circadian photoentrainment, demonstrating the feasibility of
      reconstructing central circuitry for vision after optic nerve damage in mature
      mammals.

PMID- 22615391
TI  - Energetics, lifestyle, and reproduction in birds.
AB  - Theoretical and empirical studies of life history aim to account for resource
      allocation to the different components of fitness: survival, growth, and
      reproduction. The pioneering evolutionary ecologist David Lack [(1968) Ecological
      Adaptations for Breeding in Birds (Methuen and Co., London)] suggested that
      reproductive output in birds reflects adaptation to environmental factors such as
      availability of food and risk of predation, but subsequent studies have not
      always supported Lack's interpretation. Here using a dataset for 980 bird species
      (Dataset S1), a phylogeny, and an explicit measure of reproductive productivity,
      we test predictions for how mass-specific productivity varies with body size,
      phylogeny, and lifestyle traits. We find that productivity varies negatively with
      body size and energetic demands of parental care and positively with extrinsic
      mortality. Specifically: (i) altricial species are 50% less productive than
      precocial species; (ii) species with female-only care of offspring are about 20%
      less productive than species with other methods of parental care; (iii)
      nonmigrants are 14% less productive than migrants; (iv) frugivores and
      nectarivores are about 20% less productive than those eating other foods; and (v)
      pelagic foragers are 40% less productive than those feeding in other habitats. A
      strong signal of phylogeny suggests that syndromes of similar life-history traits
      tend to be conservative within clades but also to have evolved independently in
      different clades. Our results generally support both Lack's pioneering studies
      and subsequent research on avian life history.

PMID- 22615392
TI  - Molecular signaling network complexity is correlated with cancer patient
      survivability.
AB  - The 5-y survival for cancer patients after diagnosis and treatment is strongly
      dependent on tumor type. Prostate cancer patients have a >99% chance of survival
      past 5 y after diagnosis, and pancreatic patients have <6% chance of survival
      past 5 y. Because each cancer type has its own molecular signaling network, we
      asked if there are "signatures" embedded in these networks that inform us as to
      the 5-y survival. In other words, are there statistical metrics of the network
      that correlate with survival? Furthermore, if there are, can such signatures
      provide clues to selecting new therapeutic targets? From the Kyoto Encyclopedia
      of Genes and Genomes Cancer Pathway database we computed several conventional and
      some less conventional network statistics. In particular we found a correlation
      (R(2) = 0.7) between degree-entropy and 5-y survival based on the Surveillance
      Epidemiology and End Results database. This correlation suggests that cancers
      that have a more complex molecular pathway are more refractory than those with
      less complex molecular pathway. We also found potential new molecular targets for
      drugs by computing the betweenness--a statistical metric of the centrality of a
      node--for the molecular networks.

PMID- 22615394
TI  - Different glutamate receptors convey feedforward and recurrent processing in
      macaque V1.
AB  - Neurons in the primary visual cortex (V1) receive feedforward input from the
      thalamus, which shapes receptive-field properties. They additionally receive
      recurrent inputs via horizontal connections within V1 and feedback from higher
      visual areas that are thought to be important for conscious visual perception.
      Here, we investigated what roles different glutamate receptors play in conveying
      feedforward and recurrent inputs in macaque V1. As a measure of recurrent
      processing, we used figure-ground modulation (FGM), the increased activity of
      neurons representing figures compared with background, which depends on feedback
      from higher areas. We found that feedforward-driven activity was strongly reduced
      by the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX),
      whereas this drug had no effect on FGM. In contrast, blockers of the NMDA
      receptor reduced FGM, whereas their effect on visually driven activity varied
      with the subunit specificity of the drug. The NMDA receptor blocker 2-amino-5
      phosphonovalerate (APV) caused a slight reduction of the visual response, whereas
      ifenprodil, which targets NMDA receptors containing the NMDA receptor NR2B
      subunit, increased the visual response. These findings demonstrate that glutamate
      receptors contribute differently to feedforward and recurrent processing in V1
      and suggest ways to selectively disrupt recurrent processing so that its role in
      visual perception can be elucidated.

PMID- 22615393
TI  - K-RAS GTPase- and B-RAF kinase-mediated T-cell tolerance defects in rheumatoid
      arthritis.
AB  - Autoantibodies to common autoantigens and neoantigens, such as IgG Fc and
      citrullinated peptides, are immunological hallmarks of rheumatoid arthritis (RA).
      We examined whether a failure in maintaining tolerance is mediated by defects in
      T-cell receptor activation threshold settings. RA T cells responded to
      stimulation with significantly higher ERK phosphorylation (P < 0.001). Gene
      expression arrays of ERK pathway members suggested a higher expression of KRAS
      and BRAF, which was confirmed by quantitative PCR (P = 0.003), Western blot, and
      flow cytometry (P < 0.01). Partial silencing of KRAS and BRAF lowered activation
      induced phosphorylated ERK levels (P < 0.01). In individual cells, levels of
      these signaling molecules correlated with ERK phosphorylation, attesting that
      their concentrations are functionally important. In confocal studies, B-RAF/K-RAS
      clustering was increased in RA T cells 2 min after T-cell receptor stimulation (P
      < 0.001). Overexpression of B-RAF and K-RAS in normal CD4 T cells amplified
      polyclonal T-cell proliferation and facilitated responses to citrullinated
      peptides. We propose that increased expression of B-RAF and K-RAS lowers T-cell
      activation thresholds in RA T cells, enabling responses to autoantigens.

PMID- 22615395
TI  - Castor oil induces laxation and uterus contraction via ricinoleic acid activating
      prostaglandin EP3 receptors.
AB  - Castor oil is one of the oldest drugs. When given orally, it has a laxative
      effect and induces labor in pregnant females. The effects of castor oil are
      mediated by ricinoleic acid, a hydroxylated fatty acid released from castor oil
      by intestinal lipases. Despite the wide-spread use of castor oil in conventional
      and folk medicine, the molecular mechanism by which ricinoleic acid acts remains
      unknown. Here we show that the EP(3) prostanoid receptor is specifically
      activated by ricinoleic acid and that it mediates the pharmacological effects of
      castor oil. In mice lacking EP(3) receptors, the laxative effect and the uterus
      contraction induced via ricinoleic acid are absent. Although a conditional
      deletion of the EP(3) receptor gene in intestinal epithelial cells did not affect
      castor oil-induced diarrhea, mice lacking EP(3) receptors only in smooth-muscle
      cells were unresponsive to this drug. Thus, the castor oil metabolite ricinoleic
      acid activates intestinal and uterine smooth-muscle cells via EP(3) prostanoid
      receptors. These findings identify the cellular and molecular mechanism
      underlying the pharmacological effects of castor oil and indicate a role of the
      EP(3) receptor as a target to induce laxative effects.

PMID- 22615397
TI  - Multiplex assay for condition-dependent changes in protein-protein interactions.
AB  - Changes in protein-protein interactions that occur in response to environmental
      cues are difficult to uncover and have been poorly characterized to date. Here we
      describe a yeast-based assay that allows many binary protein interactions to be
      assessed in parallel and under various conditions. This method combines molecular
      bar-coding and tag array technology with the murine dihydrofolate reductase-based
      protein-fragment complementation assay. A total of 238 protein-fragment
      complementation assay strains, each representing a unique binary protein complex,
      were tagged with molecular barcodes, pooled, and then interrogated against a
      panel of 80 diverse small molecules. Our method successfully identified specific
      disruption of the Hom3:Fpr1 interaction by the immunosuppressant FK506,
      illustrating the assay's capacity to identify chemical inhibitors of protein
      protein interactions. Among the additional findings was specific cellular
      depletion of the Dst1:Rbp9 complex by the anthracycline drug doxorubicin, but not
      by the related drug idarubicin. The assay also revealed chemical-induced
      accumulation of several binary multidrug transporter complexes that largely
      paralleled increases in transcript levels. Further assessment of two such
      interactions (Tpo1:Pdr5 and Snq2:Pdr5) in the presence of 1,246 unique chemical
      compounds revealed a positive correlation between drug lipophilicity and the drug
      response in yeast.

PMID- 22615396
TI  - Genome-wide association mapping of leaf metabolic profiles for dissecting complex
      traits in maize.
AB  - The diversity of metabolites found in plants is by far greater than in most other
      organisms. Metabolic profiling techniques, which measure many of these compounds
      simultaneously, enabled investigating the regulation of metabolic networks and
      proved to be useful for predicting important agronomic traits. However, little is
      known about the genetic basis of metabolites in crops such as maize. Here, a set
      of 289 diverse maize inbred lines was genotyped with 56,110 SNPs and assayed for
      118 biochemical compounds in the leaves of young plants, as well as for agronomic
      traits of mature plants in field trials. Metabolite concentrations had on average
      a repeatability of 0.73 and showed a correlation pattern that largely reflected
      their functional grouping. Genome-wide association mapping with correction for
      population structure and cryptic relatedness identified for 26 distinct
      metabolites strong associations with SNPs, explaining up to 32.0% of the observed
      genetic variance. On nine chromosomes, we detected 15 distinct SNP-metabolite
      associations, each of which explained more then 15% of the genetic variance. For
      lignin precursors, including p-coumaric acid and caffeic acid, we found strong
      associations (P values   to  ) with a region on chromosome 9 harboring cinnamoyl
      CoA reductase, a key enzyme in monolignol synthesis and a target for improving
      the quality of lignocellulosic biomass by genetic engineering approaches.
      Moreover, lignin precursors correlated significantly with lignin content, plant
      height, and dry matter yield, suggesting that metabolites represent promising
      connecting links for narrowing the genotype-phenotype gap of complex agronomic
      traits.

PMID- 22615399
TI  - QnAs with Shu Chien. Interview by Sandeep Ravindran.

PMID- 22615398
TI  - Structural basis for homeodomain recognition by the cell-cycle regulator Geminin.
AB  - Homeodomain-containing transcription factors play a fundamental role in the
      regulation of numerous developmental and cellular processes. Their multiple
      regulatory functions are accomplished through context-dependent inputs of target
      DNA sequences and collaborating protein partners. Previous studies have well
      established the sequence-specific DNA binding to homeodomains; however, little is
      known about how protein partners regulate their functions through targeting
      homeodomains. Here we report the solution structure of the Hox homeodomain in
      complex with the cell-cycle regulator, Geminin, which inhibits Hox
      transcriptional activity and enrolls Hox in cell proliferative control. Side
      chain carboxylates of glutamates and aspartates in the C terminus of Geminin
      generate an overall charge pattern resembling the DNA phosphate backbone. These
      residues provide electrostatic interactions with homeodomain, which combine with
      the van der Waals contacts to form the stereospecific complex. We further showed
      that the interaction with Geminin is homeodomain subclass-selective and Hox
      paralog-specific, which relies on the stapling role of residues R43 and M54 in
      helix III and the basic amino acid cluster in the N terminus. Interestingly, we
      found that the C-terminal residue Ser184 of Geminin could be phosphorylated by
      Casein kinase II, resulting in the enhanced binding to Hox and more potent
      inhibitory effect on Hox transcriptional activity, indicating an additional layer
      of regulation. This structure provides insight into the molecular mechanism
      underlying homeodomain-protein recognition and may serve as a paradigm for
      interactions between homeodomains and DNA-competitive peptide inhibitors.

PMID- 22615400
TI  - CD69 guides CD4+ T cells to the seat of memory.

PMID- 22615401
TI  - Contributions of cultural services to the ecosystem services agenda.
AB  - Cultural ecosystem services (ES) are consistently recognized but not yet
      adequately defined or integrated within the ES framework. A substantial body of
      models, methods, and data relevant to cultural services has been developed within
      the social and behavioral sciences before and outside of the ES approach. A
      selective review of work in landscape aesthetics, cultural heritage, outdoor
      recreation, and spiritual significance demonstrates opportunities for
      operationally defining cultural services in terms of socioecological models,
      consistent with the larger set of ES. Such models explicitly link ecological
      structures and functions with cultural values and benefits, facilitating
      communication between scientists and stakeholders and enabling economic,
      multicriterion, deliberative evaluation and other methods that can clarify
      tradeoffs and synergies involving cultural ES. Based on this approach, a common
      representation is offered that frames cultural services, along with all ES, by
      the relative contribution of relevant ecological structures and functions and by
      applicable social evaluation approaches. This perspective provides a foundation
      for merging ecological and social science epistemologies to define and integrate
      cultural services better within the broader ES framework.

PMID- 22615402
TI  - Release of dendritic cells from cognate CD4+ T-cell recognition results in
      impaired peripheral tolerance and fatal cytotoxic T-cell mediated autoimmunity.
AB  - Resting dendritic cells (DCs) induce tolerance of peripheral T cells that have
      escaped thymic negative selection and thus contribute significantly to protection
      against autoimmunity. We recently showed that CD4(+)Foxp3(+) regulatory T cells
      (Tregs) are important for maintaining the steady-state phenotype of DCs and their
      tolerizing capacity in vivo. We now provide evidence that DC activation in the
      absence of Tregs is a direct consequence of missing DC-Treg interactions rather
      than being secondary to generalized autoimmunity in Treg-less mice. We show that
      DCs that lack MHC class II and thus cannot make cognate interactions with CD4(+)
      T cells are completely unable to induce peripheral CD8(+) T-cell tolerance.
      Consequently, mice in which interactions between DC and CD4(+) T cells are not
      possible develop spontaneous and fatal cytotoxic T lymphocyte-mediated
      autoimmunity.

PMID- 22615403
TI  - Mechanisms of damage to corals exposed to sedimentation.
AB  - We investigated the mechanisms leading to rapid death of corals when exposed to
      runoff and resuspended sediments, postulating that the killing was microbially
      mediated. Microsensor measurements were conducted in mesocosm experiments and in
      naturally accumulated sediment on corals. In organic-rich, but not in organic
      poor sediment, pH and oxygen started to decrease as soon as the sediment
      accumulated on the coral. Organic-rich sediments caused tissue degradation within
      1 d, whereas organic-poor sediments had no effect after 6 d. In the harmful
      organic-rich sediment, hydrogen sulfide concentrations were low initially but
      increased progressively because of the degradation of coral mucus and dead
      tissue. Dark incubations of corals showed that separate exposures to darkness,
      anoxia, and low pH did not cause mortality within 4 d. However, the combination
      of anoxia and low pH led to colony death within 24 h. When hydrogen sulfide was
      added after 12 h of anoxia and low pH, colonies died after an additional 3 h. We
      suggest that sedimentation kills corals through microbial processes triggered by
      the organic matter in the sediments, namely respiration and presumably
      fermentation and desulfurylation of products from tissue degradation. First,
      increased microbial respiration results in reduced O(2) and pH, initiating tissue
      degradation. Subsequently, the hydrogen sulfide formed by bacterial decomposition
      of coral tissue and mucus diffuses to the neighboring tissues, accelerating the
      spread of colony mortality. Our data suggest that the organic enrichment of
      coastal sediments is a key process in the degradation of coral reefs exposed to
      terrestrial runoff.

PMID- 22615404
TI  - Empoasca leafhoppers attack wild tobacco plants in a jasmonate-dependent manner
      and identify jasmonate mutants in natural populations.
AB  - Choice of host plants by phytophagous insects is essential for their survival and
      reproduction. This choice involves complex behavioral responses to a variety of
      physical and chemical characteristics of potential plants for feeding. For
      insects of the order Hemiptera, these behavioral responses involve a series of
      steps including labial dabbing and probing using their piercing mouthparts. These
      initial probing and feeding attempts also elicit a rapid accumulation of
      phytohormones, such as jasmonic acid (JA), and the induced defense metabolites
      they mediate. When Nicotiana attenuata plants are rendered JA deficient by
      silencing the initial committed step of the JA biosynthesis pathway, they are
      severely attacked in nature by hemipteran leafhoppers of the genus Empoasca. By
      producing N. attenuata plants silenced in multiple steps of JA biosynthesis and
      perception and in the biosynthesis of the plant's three major classes of JA
      inducible insecticidal defenses, we demonstrate that the choice of plants for
      feeding by Empoasca leafhoppers in both nature and the glasshouse is independent
      of the accumulation of major insecticidal molecules. Moreover, this choice is
      independent of the presence of Candidatus Phytoplasma spp. and is not associated
      with detectable changes in plant volatiles but instead depends on the plant's
      capacity to mediate JA signaling. We exploited this trait and used Empoasca
      leafhoppers to reveal genetic variation in JA accumulation and signaling hidden
      in N. attenuata natural populations.

PMID- 22615406
TI  - Divergent responses to spring and winter warming drive community level flowering
      trends.
AB  - Analyses of datasets throughout the temperate midlatitude regions show a
      widespread tendency for species to advance their springtime phenology, consistent
      with warming trends over the past 20-50 y. Within these general trends toward
      earlier spring, however, are species that either have insignificant trends or
      have delayed their timing. Various explanations have been offered to explain this
      apparent nonresponsiveness to warming, including the influence of other abiotic
      cues (e.g., photoperiod) or reductions in fall/winter chilling (vernalization).
      Few studies, however, have explicitly attributed the historical trends of
      nonresponding species to any specific factor. Here, we analyzed long-term data on
      phenology and seasonal temperatures from 490 species on two continents and
      demonstrate that (i) apparent nonresponders are indeed responding to warming, but
      their responses to fall/winter and spring warming are opposite in sign and of
      similar magnitude; (ii) observed trends in first flowering date depend strongly
      on the magnitude of a given species' response to fall/winter vs. spring warming;
      and (iii) inclusion of fall/winter temperature cues strongly improves hindcast
      model predictions of long-term flowering trends compared with models with spring
      warming only. With a few notable exceptions, climate change research has focused
      on the overall mean trend toward phenological advance, minimizing discussion of
      apparently nonresponding species. Our results illuminate an understudied source
      of complexity in wild species responses and support the need for models
      incorporating diverse environmental cues to improve predictability of community
      level responses to anthropogenic climate change.

PMID- 22615405
TI  - Reprogramming of proline and glutamine metabolism contributes to the
      proliferative and metabolic responses regulated by oncogenic transcription factor
      c-MYC.
AB  - In addition to glycolysis, the oncogenic transcription factor c-MYC (MYC)
      stimulates glutamine catabolism to fuel growth and proliferation of cancer cells
      through up-regulating glutaminase (GLS). Glutamine is converted to glutamate by
      GLS, entering the tricarboxylic acid cycle as an important energy source. Less
      well-recognized, glutamate can also be converted to proline through Delta(1)
      pyrroline-5-carboxylate (P5C) and vice versa. This study suggests that some MYC
      induced cellular effects are due to MYC regulation of proline metabolism. Proline
      oxidase, also known as proline dehydrogenase (POX/PRODH), the first enzyme in
      proline catabolism, is a mitochondrial tumor suppressor that inhibits
      proliferation and induces apoptosis. MiR-23b* mediates POX/PRODH down-regulation
      in human kidney tumors. MiR-23b* is processed from the same transcript as miR
      23b; the latter inhibits the translation of GLS. Using MYC-inducible human
      Burkitt lymphoma model P493 and PC3 human prostate cancer cells, we showed that
      MYC suppressed POX/PRODH expression primarily through up-regulating miR-23b*. The
      growth inhibition in the absence of MYC was partially reversed by POX/PRODH
      knockdown, indicating the importance of suppression of POX/PRODH in MYC-mediated
      cellular effects. Interestingly, MYC not only inhibited POX/PRODH, but also
      markedly increased the enzymes of proline biosynthesis from glutamine, including
      P5C synthase and P5C reductase 1. MYC-induced proline biosynthesis from glutamine
      was directly confirmed using (13)C,(15)N-glutamine as a tracer. The metabolic
      link between glutamine and proline afforded by MYC emphasizes the complexity of
      tumor metabolism. Further studies of the relationship between glutamine and
      proline metabolism should provide a deeper understanding of tumor metabolism
      while enabling the development of novel therapeutic strategies.

PMID- 22615407
TI  - Quantification of the relative roles of niche and neutral processes in
      structuring gastrointestinal microbiomes.
AB  - The theoretical description of the forces that shape ecological communities
      focuses around two classes of models. In niche theory, deterministic interactions
      between species, individuals, and the environment are considered the dominant
      factor, whereas in neutral theory, stochastic forces, such as demographic noise,
      speciation, and immigration, are dominant. Species abundance distributions
      predicted by the two classes of theory are difficult to distinguish empirically,
      making it problematic to deduce ecological dynamics from typical measures of
      diversity and community structure. Here, we show that the fusion of species
      abundance data with genome-derived measures of evolutionary distance can provide
      a clear indication of ecological dynamics, capable of quantifying the relative
      roles played by niche and neutral forces. We apply this technique to six
      gastrointestinal microbiomes drawn from three different domesticated vertebrates,
      using high-resolution surveys of microbial species abundance obtained from
      carefully curated deep 16S rRNA hypervariable tag sequencing data. Although the
      species abundance patterns are seemingly well fit by the neutral theory of
      metacommunity assembly, we show that this theory cannot account for the
      evolutionary patterns in the genomic data; moreover, our analyses strongly
      suggest that these microbiomes have, in fact, been assembled through processes
      that involve a significant nonneutral (niche) contribution. Our results
      demonstrate that high-resolution genomics can remove the ambiguities of process
      inference inherent in classic ecological measures and permits quantification of
      the forces shaping complex microbial communities.

PMID- 22615408
TI  - Asymmetric forest transition driven by the interaction of socioeconomic
      development and environmental heterogeneity in Central America.
AB  - Forest transitions (FT) have been observed in many developed countries and more
      recently in the developing world. However, our knowledge of FT from tropical
      regions is mostly derived from case studies from within a particular country,
      making it difficult to generalize findings across larger regions. Here we
      overcome these difficulties by conducting a recent (2001-2010) satellite-based
      analysis of trends in forest cover across Central America, stratified by biomes,
      which we related to socioeconomic variables associated with human development.
      Results show a net decrease of woody vegetation resulting from 12,201 km(2) of
      deforestation of moist forests and 6,825 km(2) of regrowth of conifer and dry
      forests. The Human Development Index was the socioeconomic variable best
      associated with forest cover change. The least-developed countries, Nicaragua and
      Guatemala, experienced both rapid deforestation of moist forests and significant
      recovery of conifer and dry forests. In contrast, the most developed countries,
      Panama and Costa Rica, had net woody vegetation gain and a more stable forest
      cover configuration. These results imply a good agreement with FT predictions of
      forest change in relation to socioeconomic development, but strong asymmetry in
      rates and directions of change largely dependent upon the biome where change is
      occurring. The FT model should be refined by incorporating ecological and
      socioeconomic heterogeneity, particularly in multicountry and regional studies.
      These asymmetric patterns of forest change should be evaluated when developing
      strategies for conserving biodiversity and environmental services.

PMID- 22615409
TI  - Shared signaling pathways among gasotransmitters.

PMID- 22615410
TI  - Primate evidence on the late health effects of early-life adversity.
AB  - This paper exploits a unique ongoing experiment to analyze the effects of early
      rearing conditions on physical and mental health in a sample of rhesus monkeys
      (Macaca mulatta). We analyze the health records of 231 monkeys that were randomly
      allocated at birth across three rearing conditions: mother rearing, peer rearing,
      and surrogate peer rearing. We show that the lack of a secure attachment
      relationship in the early years engendered by adverse rearing conditions has
      detrimental long-term effects on health that are not compensated for by a normal
      social environment later in life.

PMID- 22615412
TI  - Notch controls the magnitude of T helper cell responses by promoting cellular
      longevity.
AB  - Generation of effective immune responses requires expansion of rare antigen
      specific CD4(+) T cells. The magnitude of the responding population is ultimately
      determined by proliferation and survival. Both processes are tightly controlled
      to limit responses to innocuous antigens. Sustained expansion occurs only when
      innate immune sensors are activated by microbial stimuli or by adjuvants, which
      has important implications for vaccination. The molecular identity of the signals
      controlling sustained T-cell responses is not fully clear. Here, we describe a
      prominent role for the Notch pathway in this process. Coactivation of Notch
      allows accumulation of far greater numbers of activated CD4(+) T cells than
      stimulation via T-cell receptor and classic costimulation alone. Notch does not
      overtly affect cell cycle entry or progression of CD4(+) T cells. Instead, Notch
      protects activated CD4(+) T cells against apoptosis after an initial phase of
      clonal expansion. Notch induces a broad antiapoptotic gene expression program
      that protects against intrinsic, as well as extrinsic, apoptosis pathways. Both
      Notch1 and Notch2 receptors and the canonical effector RBPJ (recombination signal
      binding protein for immunoglobulin kappa J region) are involved in this process.
      Correspondingly, CD4(+) T-cell responses to immunization with protein antigen are
      strongly reduced in mice lacking these components of the Notch pathway. Our
      findings, therefore, show that Notch controls the magnitude of CD4(+) T-cell
      responses by promoting cellular longevity.

PMID- 22615413
TI  - Model for MLL translocations in therapy-related leukemia involving topoisomerase
      IIbeta-mediated DNA strand breaks and gene proximity.
AB  - Topoisomerase poisons such as the epipodophyllotoxin etoposide are widely used
      effective cytotoxic anticancer agents. However, they are associated with the
      development of therapy-related acute myeloid leukemias (t-AMLs), which display
      characteristic balanced chromosome translocations, most often involving the mixed
      lineage leukemia (MLL) locus at 11q23. MLL translocation breakpoints in t-AMLs
      cluster in a DNase I hypersensitive region, which possesses cryptic promoter
      activity, implicating transcription as well as topoisomerase II activity in the
      translocation mechanism. We find that 2-3% of MLL alleles undergoing
      transcription do so in close proximity to one of its recurrent translocation
      partner genes, AF9 or AF4, consistent with their sharing transcription factories.
      We show that most etoposide-induced chromosome breaks in the MLL locus and the
      overall genotoxicity of etoposide are dependent on topoisomerase IIbeta, but that
      topoisomerase IIalpha and -beta occupancy and etoposide-induced DNA cleavage data
      suggest factors other than local topoisomerase II concentration determine
      specific clustering of MLL translocation breakpoints in t-AML. We propose a model
      where DNA double-strand breaks (DSBs) introduced by topoisomerase IIbeta into
      pairs of genes undergoing transcription within a common transcription factory
      become stabilized by antitopoisomerase II drugs such as etoposide, providing the
      opportunity for illegitimate end joining and translocation.

PMID- 22615414
TI  - Thrips pollination of Mesozoic gymnosperms.
AB  - Within modern gymnosperms, conifers and Ginkgo are exclusively wind pollinated
      whereas many gnetaleans and cycads are insect pollinated. For cycads, thrips are
      specialized pollinators. We report such a specialized pollination mode from Early
      Cretaceous amber of Spain, wherein four female thrips representing a genus and
      two species in the family Melanthripidae were covered by abundant Cycadopites
      pollen grains. These females bear unique ring setae interpreted as specialized
      structures for pollen grain collection, functionally equivalent to the hook
      tipped sensilla and plumose setae on the bodies of bees. The most parsimonious
      explanation for this structure is parental food provisioning for larvae,
      indicating subsociality. This association provides direct evidence of specialized
      collection and transportation of pollen grains and likely gymnosperm pollination
      by 110-105 million years ago, possibly considerably earlier.

PMID- 22615415
TI  - Evolutionary optimum for male sexual traits characterized using the multivariate
      Robertson-Price Identity.
AB  - Phenotypes tend to remain relatively constant in natural populations, suggesting
      a limit to trait evolution. Although stationary phenotypes suggest stabilizing
      selection, directional selection is more commonly reported. However, selection on
      phenotypes will have no evolutionary consequence if the traits do not genetically
      covary with fitness, a covariance known as the Robertson-Price Identity. The
      nature of this genetic covariance determines if phenotypes will evolve
      directionally or whether they reside at an evolutionary optimum. Here, we show
      how a set of traits can be shown to be under net stabilizing selection through an
      application of the multivariate Robertson-Price Identity. We characterize how a
      suite of male sexual displays genetically covaries with fitness in a population
      of Drosophila serrata. Despite strong directional sexual selection on these
      phenotypes directly and significant genetic variance in them, little genetic
      covariance was detected with overall fitness. Instead, genetic analysis of trait
      deviations showed substantial stabilizing selection on the genetic variance of
      these traits with respect to overall fitness, indicating that they reside at an
      evolutionary optimum. In the presence of widespread pleiotropy, stabilizing
      selection on focal traits will arise through the net effects of selection on
      other, often unmeasured, traits and will tend to be stronger on trait
      combinations than single traits. Such selection may be difficult to detect in
      phenotypic analyses if the environmental covariance between the traits and
      fitness obscures the underlying genetic associations. The genetic analysis of
      trait deviations provides a way of detecting the missing stabilizing selection
      inferred by recent metaanalyses.

PMID- 22615417
TI  - Neurological picture. Vertical 'half-and-a-half' syndrome.

PMID- 22615416
TI  - Inhibition of serine palmitoyltransferase delays the onset of radiation-induced
      pulmonary fibrosis through the negative regulation of sphingosine kinase-1
      expression.
AB  - The enforcement of sphingosine-1-phosphate (S1P) signaling network protects from
      radiation-induced pneumonitis. We now demonstrate that, in contrast to early
      postirradiation period, late postirradiation sphingosine kinase-1 (SphK1) and
      sphingoid base-1-phosphates are associated with radiation-induced pulmonary
      fibrosis (RIF). Using the mouse model, we demonstrate that RIF is characterized
      by a marked upregulation of S1P and dihydrosphingosine-1-phosphate (DHS1P) levels
      in the lung tissue and in circulation accompanied by increased lung SphK1
      expression and activity. Inhibition of sphingolipid de novo biosynthesis by
      targeting serine palmitoyltransferase (SPT) with myriocin reduced radiation
      induced pulmonary inflammation and delayed the onset of RIF as evidenced by
      increased animal lifespan and decreased expression of markers of fibrogenesis,
      such as collagen and alpha-smooth muscle actin (alpha-SMA), in the lung. Long
      term inhibition of SPT also decreased radiation-induced SphK activity in the lung
      and the levels of S1P-DHS1P in the lung tissue and in circulation. In vitro,
      inhibition or silencing of serine palmitoyltransferase attenuated transforming
      growth factor-beta1 (TGF-beta)-induced upregulation of alpha-SMA through the
      negative regulation of SphK1 expression in normal human lung fibroblasts. These
      data demonstrate a novel role for SPT in regulating TGF-beta signaling and
      fibrogenesis that is linked to the regulation of SphK1 expression and S1P-DHS1P
      formation.

PMID- 22615418
TI  - Compression of morbidity outcomes key to investment in public health.

PMID- 22615419
TI  - Deprivation-based inequalities in under-18 conception rates and the proportion of
      under-18 conceptions leading to abortion in England, 1998-2010.
AB  - BACKGROUND: In 1999, the UK Government launched a strategy to reduce teenage
      pregnancy and geographical inequalities in teenage conception rates. This study
      investigates how associations between deprivation and under-18 conceptions, along
      with subsequent abortions, since changed as teenage pregnancy rates fell.
      METHODS: A data set was constructed from local authority Indices of Multiple
      Deprivation (IMD) scores and routine data on under-18 conception rates and the
      proportion of under-18 conceptions leading to abortion from 1998 to 2010.
      Correlation analysis (Pearson's r) was used to measure the association between
      each period of conception and abortion data and the relevant version of the IMD.
      Changes in these correlations over the period were tested for statistical
      significance. RESULTS: There remained a strong association between IMD and under
      18 conception rates from 1998 (r = 0.782, P< 0.0001) to 2010 (r = 0.817, P<
      0.0001) with no statistically significant change. A statistically significant
      decrease occurred in the inverse association between IMD and the proportion of
      under-18 conceptions leading to abortion from 1998 (r = -0.501, P< 0.0001) to
      2010 (r = -0.332, P< 0.0001) CONCLUSIONS: While under-18 conceptions fell from
      1998 to 2010, inequalities in rates between the most and least deprived local
      authorities remained undiminished. At the same time, abortion became an
      increasingly common outcome of under-18 conceptions.

PMID- 22615420
TI  - Do hybrid procedures have proven clinical utility and are they the wave of the
      future? : hybrid procedures have proven clinical utility and are the wave of the
      future.

PMID- 22615421
TI  - Do hybrid procedures have proven clinical utility and are they the wave of the
      future? : hybrid procedures have no proven clinical utility and are not the wave
      of the future.

PMID- 22615422
TI  - Sudden cardiac death in the athlete: bridging the gaps between evidence, policy,
      and practice.

PMID- 22615423
TI  - Hoarseness and chest pain in Eisenmenger syndrome with pulmonary artery aneurysm.

PMID- 22615424
TI  - Ortner syndrome associated with aortic pseudoaneurysm after repair of aortic
      coarctation 30 years previously.

PMID- 22615425
TI  - Novel risk factors for atrial fibrillation: useful for risk prediction and
      clinical decision making?

PMID- 22615427
TI  - Letter by Uzun et al regarding article, "comparison of transplacental treatment
      of fetal supraventricular tachyarrhythmias with digoxin, flecainide, and sotalol:
      results of a nonrandomized multicenter study".

PMID- 22615428
TI  - A-type K+ channels encoded by Kv4.2, Kv4.3 and Kv1.4 differentially regulate
      intrinsic excitability of cortical pyramidal neurons.
AB  - Rapidly activating and rapidly inactivating voltage-gated A-type K+ currents, IA,
      are key determinants of neuronal excitability and several studies suggest a
      critical role for the Kv4.2 pore-forming alpha subunit in the generation of IA
      channels in hippocampal and cortical pyramidal neurons. The experiments here
      demonstrate that Kv4.2, Kv4.3 and Kv1.4 all contribute to the generation of IA
      channels in mature cortical pyramidal (CP) neurons and that Kv4.2-, Kv4.3- and
      Kv1.4-encoded IA channels play distinct roles in regulating the intrinsic
      excitability and the firing properties of mature CP neurons. In vivo loss of
      Kv4.2, for example, alters the input resistances, current thresholds for action
      potential generation and action potential repolarization of mature CP neurons.
      Elimination of Kv4.3 also prolongs action potential duration, whereas the input
      resistances and the current thresholds for action potential generation in Kv4.3-/
      and WT CP neurons are indistinguishable. In addition, although increased
      repetitive firing was observed in both Kv4.2-/- and Kv4.3-/- CP neurons, the
      increases in Kv4.2-/- CP neurons were observed in response to small, but not
      large, amplitude depolarizing current injections, whereas firing rates were
      higher in Kv4.3-/- CP neurons only with large amplitude current injections. In
      vivo loss of Kv1.4, in contrast, had minimal effects on the intrinsic
      excitability and the firing properties of mature CP neurons. Comparison of the
      effects of pharmacological blockade of Kv4-encoded currents in Kv1.4-/- and WT CP
      neurons, however, revealed that Kv1.4-encoded IA channels do contribute to
      controlling resting membrane potentials, the regulation of current thresholds for
      action potential generation and repetitive firing rates in mature CP neurons.

PMID- 22615429
TI  - ROS and SOCE: recent advances and controversies in the regulation of STIM and
      Orai.
AB  - Store-operated Ca(2+) entry (SOCE) is a widespread mechanism in cells to raise
      cytosolic Ca(2+) and to refill Ca(2+) stores. T cells critically rely on SOCE
      mediated by stromal interaction molecules (STIM) and Orai molecules for their
      activation and regulation of gene transcription; cells such as muscle cells,
      neurons or melanocytes probably utilize SOCE for the transmission of inducible
      receptor-mediated function as well as for generalized Ca(2+) homeostasis
      mechanisms. Exposure to environmental or cell-intrinisic reactive oxygen species
      (ROS) can affect several components involved in Ca(2+) homeostasis and thus alter
      multiple pathways. While all cells have a capacity to produce intracellular ROS,
      exposure of immune and skin cells to extracellular oxidative stress is
      particularly high during inflammation and/or with UV exposure. This review
      briefly summarizes cell-intrinsic sources of ROS and focuses on current findings
      and controversies regarding the regulation of STIM and Orai by oxidative
      modifications. We also introduce melanocytes as a new model system to study the
      function of STIM and Orai isoforms under physiological conditions that include
      exposure to UV light as an activating stimulus.

PMID- 22615430
TI  - Requirement of neuronal connexin36 in pathways mediating presynaptic inhibition
      of primary afferents in functionally mature mouse spinal cord.
AB  - Electrical synapses formed by gap junctions containing connexin36 (Cx36) promote
      synchronous activity of interneurones in many regions of mammalian brain;
      however, there is limited information on the role of electrical synapses in
      spinal neuronal networks. Here we show that Cx36 is widely distributed in the
      spinal cord and is involved in mechanisms that govern presynaptic inhibition of
      primary afferent terminals. Electrophysiological recordings were made in spinal
      cord preparations from 8- to 11-day-old wild-type and Cx36 knockout mice. Several
      features associated with presynaptic inhibition evoked by conditioning
      stimulation of low threshold hindlimb afferents were substantially compromised in
      Cx36 knockout mice. Dorsal root potentials (DRPs) evoked by low intensity
      stimulation of sensory afferents were reduced in amplitude by 79% and in duration
      by 67% in Cx36 knockouts. DRPs were similarly affected in wild-types by bath
      application of gap junction blockers. Consistent with presynaptic inhibition of
      group Ia muscle spindle afferent terminals on motoneurones described in adult
      cats, conditioning stimulation of an adjacent dorsal root evoked a long duration
      inhibition of monosynaptic reflexes recorded from the ventral root in wild-type
      mice, and this inhibition was antagonized by bicuculline. The same conditioning
      stimulation failed to inhibit monosynaptic reflexes in Cx36 knockout mice.
      Immunofluorescence labelling for Cx36 was found throughout the dorsal and ventral
      horns of the spinal cord of juvenile mice and persisted in mature animals. In
      deep dorsal horn laminae, where interneurones involved in presynaptic inhibition
      of large diameter muscle afferents are located, cells were extensively dye
      coupled following intracellular neurobiotin injection. Coupled cells displayed
      Cx36-positive puncta along their processes. Our results indicate that gap
      junctions formed by Cx36 in spinal cord are required for maintenance of
      presynaptic inhibition, including the regulation of transmission from Ia muscle
      spindle afferents. In addition to a role in presynaptic inhibition in juvenile
      animals, the persistence of Cx36 expression among spinal neuronal populations in
      the adult mouse suggests that the contribution of electrical synapses to
      integrative processes in fully mature spinal cord may be as diverse as that found
      in other areas of the CNS.

PMID- 22615431
TI  - The role of the paraventricular nucleus of the hypothalamus in the regulation of
      cardiac and renal sympathetic nerve activity in conscious normal and heart
      failure sheep.
AB  - The paraventricular nucleus of the hypothalamus (PVN) plays a major role in
      central cardiovascular and volume control, and has been implicated in controlling
      sympathetic nerve activity (SNA) during volume expansion and in heart failure
      (HF). The objectives were to determine the role of the PVN on cardiac and renal
      SNA (CSNA and RSNA) in conscious normal sheep and sheep with pacing-induced heart
      failure. In normovolaemic sheep in the normal state and in HF, bilateral
      microinjection of the GABA agonist muscimol (2 mm, 500 nl), had no effects on
      resting mean arterial pressure (MAP), heart rate (HR), CSNA or RSNA. In addition,
      neither chemical inhibition of the PVN using the inhibitory amino acid glycine
      (0.5 m, 500 nl), nor electrolytic lesion of the PVN reduced the elevated level of
      CSNA in HF. Dysinhibition of the PVN with bilateral microinjection of bicuculline
      (1 mm, 500 nl) in normal sheep increased MAP, HR and CSNA, but decreased RSNA,
      whereas in HF bicuculline had no effects on MAP, HR or CSNA, but inhibited RSNA.
      During volume expansion in normal sheep, muscimol reversed the inhibition of
      RSNA, but not of CSNA. In summary, removal of endogenous GABAergic inhibition to
      the PVN indicated that CSNA is normally under inhibitory control. Although this
      inhibition was absent in HF, the responses to pharmacological inhibition, or
      lesion of the PVN, indicates that it does not drive the increased CSNA in HF.
      These findings indicate the PVN has a greater influence on RSNA than CSNA in the
      resting state in normal and HF sheep, and during volume expansion in normal
      sheep.

PMID- 22615432
TI  - Roles of individual prolyl-4-hydroxylase isoforms in the first 24 hours following
      transient focal cerebral ischaemia: insights from genetically modified mice.
AB  - This study investigated the function of each of the hypoxia inducible factor
      (HIF) prolyl-4-hydroxylase enzymes (PHD1-3) in the first 24 h following transient
      focal cerebral ischaemia by using mice with each isoform genetically suppressed.
      Male, 8- to 12-week old PHD1-/-, PHD2+/- and PHD3-/- mice and their wild-type
      (WT) littermate were subjected to 45 min of middle cerebral artery occlusion
      (MCAO). During the experiments, regional cerebral blood flow (rCBF) was recorded
      by laser Doppler flowmetry. Behaviour was assessed at both 2 h and 24 h after
      reperfusion with a common neuroscore. Infarct volumes, blood-brain barrier (BBB)
      disruption, cerebral vascular density, apoptosis, reactive oxygen species (ROS),
      HIF1alpha, and glycogen levels were then determined using histological and
      immunohistochemical techniques. When compared to their WT littermates, PHD2+/-
      mice had significantly increased cerebral microvascular density and more
      effective restoration of CBF upon reperfusion. PHD2+/- mice showed significantly
      better functional outcomes and higher activity rates at both 2 h and 24 h after
      MCAO, associated with significant fewer apoptotic cells in the penumbra and less
      BBB disruption; PHD3-/- mice had impaired rCBF upon early reperfusion but
      comparable functional outcomes; PHD1-/- mice did not show any significant changes
      following the MCAO. Production of ROS, HIF1alpha staining and glycogen content in
      the brain were not different in any comparison. Life-long genetic inhibition of
      PHD enzymes produces different effects on outcome in the first 24 h after
      transient cerebral ischaemia. These need to be considered in optimizing
      therapeutic effects of PHD inhibitors, particularly when isoform specific
      inhibitors become available.

PMID- 22615433
TI  - The human carotid body transcriptome with focus on oxygen sensing and
      inflammation--a comparative analysis.
AB  - The carotid body (CB) is the key oxygen sensing organ. While the expression of CB
      specific genes is relatively well studied in animals, corresponding data for the
      human CB are missing. In this study we used five surgically removed human CBs to
      characterize the CB transcriptome with microarray and PCR analyses, and compared
      the results with mice data. In silico approaches demonstrated a unique gene
      expression profile of the human and mouse CB transcriptomes and an unexpected
      upregulation of both human and mouse CB genes involved in the inflammatory
      response compared to brain and adrenal gland data. Human CBs express most of the
      genes previously proposed to be involved in oxygen sensing and signalling based
      on animal studies, including NOX2, AMPK, CSE and oxygen sensitive K+ channels. In
      the TASK subfamily of K+ channels, TASK-1 is expressed in human CBs, while TASK-3
      and TASK-5 are absent, although we demonstrated both TASK-1 and TASK-3 in one of
      the mouse reference strains. Maxi-K was expressed exclusively as the spliced
      variant ZERO in the human CB. In summary, the human CB transcriptome shares
      important features with the mouse CB, but also differs significantly in the
      expression of a number of CB chemosensory genes. This study provides key
      information for future functional investigations on the human carotid body.

PMID- 22615434
TI  - Acute and chronic effects of carotid body denervation on ventilation and
      chemoreflexes in three rat strains.
AB  - Brown Norway (BN) rats have a relatively specific deficit in CO2 sensitivity.
      This deficit could be due to an abnormally weak carotid body contribution to CO2
      sensitivity. Accordingly, we tested the hypothesis that CBD would have less of an
      effect on eupnoeic breathing and CO2 sensitivity in the BN rats compared to other
      rat strains.We measured ventilation and blood gases at rest (eupnoea) and during
      hypoxia (FIO2 =0.12) or hypercapnia (FICO2 =0.07) before and up to 23 days after
      bilateral or Sham CBD in BN, Sprague-Dawley (SD) and Dahl Salt-Sensitive (SS)
      rats. In all three rat strains, CBD elicited eupnoeic hypoventilation (PaCO2 +8.7
      11.0 mmHg) 1-2 days post-CBD (P <0.05), and attenuated ventilatory responses to
      hypoxia (P <0.05) and venous sodium cyanide (NaCN; P<0.05), while sham CBD had no
      effect on resting breathing, blood gases or chemoreflexes (P >0.05). In contrast,
      CBD had no effect on CO2 sensitivity (VE/PaCO2) in all strains (P>0.05). Eupnoeic
      PaCO2 returned to pre-CBD values within 15-23 days post-CBD. Thus, the effects of
      CBD in rats (1) further support an important role for the carotid bodies in
      eupnoeic blood gas regulation, (2) suggest that the carotid bodies are not a
      major determinant of CO2 sensitivity in rats, and (3) may not support the concept
      of an interaction among the peripheral and central chemoreceptors in rats.

PMID- 22615436
TI  - An analysis of deformation-dependent electromechanical coupling in the mouse
      heart.
AB  - To investigate the effects of the coupling between excitation and contraction on
      whole-organ function, we have developed a novel biophysically based multiscale
      electromechanical model of the murine heart. Through comparison with a
      comprehensive in vivo experimental data set, we show good agreement with pressure
      and volume measurements at both physiological temperatures and physiological
      pacing frequencies. This whole-organ model was used to investigate the effects of
      material and haemodynamic properties introduced at the tissue level, as well as
      emergent function of our novel cell contraction model. Through a comprehensive
      sensitivity analysis at both the cellular and whole organ level, we demonstrate
      the sensitivity of the model's results to its parameters and the constraining
      effect of experimental data. These results demonstrate the fundamental importance
      of length- and velocity-dependent feedback to the cellular scale for whole-organ
      function, and we show that a strong velocity dependence of tension is essential
      for explaining the differences between measured single cell tension and whole
      organ pressure transients.

PMID- 22615435
TI  - Regulation of lymphocyte function by ORAI and STIM proteins in infection and
      autoimmunity.
AB  - Store-operated Ca(2+) entry (SOCE) in cells of the immune system is mediated by
      Ca(2+) release-activated Ca(2+) (CRAC) channels that are formed by ORAI1 and its
      homologues ORAI2 and ORAI3. They are activated by stromal interaction molecules
      (STIM) 1 and 2 in response to depletion of endoplasmic reticulum Ca(2+) stores.
      Loss-of-function mutations in the human ORAI1 and STIM1 genes abolish CRAC
      channel function and SOCE in a variety of non-excitable cells including
      lymphocytes and other immune cells, resulting in a unique clinical syndrome
      termed CRAC channelopathy. It is dominated by severe immunodeficiency and
      autoimmunity due to impaired SOCE and defects in the function of several
      lymphocyte subsets. These include CD8(+) T cells, CD4(+) effector and regulatory
      T cells, natural killer (NK) cells and B cells. This review provides a concise
      discussion of the role of CRAC channels in these lymphocyte populations and the
      regulation of adaptive immune responses to infection, in autoimmunity and
      inflammation.

PMID- 22615437
TI  - Plasticity of NMDA receptor-mediated excitatory postsynaptic currents at
      perforant path inputs to dendrite-targeting interneurons.
AB  - Synaptic plasticity of NMDA receptors (NMDARs) has been recently described in a
      number of brain regions and we have previously characterised LTP and LTD of
      glutamatergic NMDA receptor-mediated EPSCs (NMDAR-EPSCs) in granule cells of
      dentate gyrus. The functional significance of NMDAR plasticity at perforant path
      synapses on hippocampal network activity depends on whether this is a common
      feature of perforant path synapses on all postsynaptic target cells or if this
      plasticity occurs only at synapses on principal cells. We recorded NMDAR-EPSCs at
      medial perforant path synapses on interneurons in dentate gyrus which had
      significantly slower decay kinetics compared to those recorded in granule cells.
      NMDAR pharmacology in interneurons was consistent with expression of both GluN2B-
      and GluN2D-containing receptors. In contrast to previously described high
      frequency stimulation-induced bidirectional plasticity of NMDAR-EPSCs in granule
      cells, only LTD of NMDAR-EPSCs was induced in interneurons in our standard
      experimental conditions. In interneurons, LTD of NMDAR-EPSCs was associated with
      a loss of sensitivity to a GluN2D-selective antagonist and was inhibited by the
      actin stabilising agent, jasplakinolide. While LTP of NMDAR-EPSCs can be readily
      induced in granule cells, this form of plasticity was only observed in
      interneurons when extracellular calcium was increased above physiological
      concentrations during HFS or when PKC was directly activated by phorbol ester,
      suggesting that opposing forms of plasticity at inputs to interneurons and
      principal cells may act to regulate granule cell dendritic integration and
      processing.

PMID- 22615438
TI  - Two GABAA responses with distinct kinetics in a sound localization circuit.
AB  - The temporal characteristics and functional diversity of GABAergic inhibition are
      determined by the spatiotemporal neurotransmitter profile, intrinsic properties
      of GABAA receptors, and other factors. Here, we report two distinct GABAA
      responses and the underlying mechanisms in neurons of the chicken nucleus
      laminaris (NL), the first encoder of interaural time difference for sound
      localization in birds. The time course of the postsynaptic GABAA currents in NL
      neurons, recorded with whole-cell voltage clamp, differed between different
      characteristic frequency (CF) regions. Compared to low-CF (LF) neurons,
      middle/high-CF (MF/HF) neurons had significantly slower IPSCs, with a 2.6-fold
      difference in the decay time constants of spontaneous IPSCs and a 5.3-fold
      difference in the decay of IPSCs elicited by single-pulse stimulus. Such
      differences were especially dramatic when IPSCs were elicited by train
      stimulations at physiologically relevant frequencies, and at high stimulus
      intensities. To account for these distinct GABAA responses, we showed that MF/HF
      neurons exhibited more prominent asynchronous release of GABA. Supporting this
      observation, replacement of extracellular Ca2+ with Sr2+ increased the decay of
      IPSCs in LF neurons, and EGTA-AM reduced the decay of IPSCs in MF/HF neurons.
      Furthermore, pharmacological evidence suggests that GABA spillover plays a
      greater role in prolonging the IPSCs of MF/HF neurons. Consequently, under whole
      cell current clamp, synaptically released GABA produced short- and long-lasting
      suppression of the neuronal excitability of LF and MF/HF neurons, respectively.
      Taken together, these results suggest that the GABAergic inputs to NL neurons may
      exert a dynamic modulation of interaural time difference (ITD) coding in a CF
      dependent manner.

PMID- 22615439
TI  - Noncardiac surgery: widening the gap in pulse pressure.

PMID- 22615440
TI  - The inhibiting effect of factor XIII on hyperfibrinolysis.

PMID- 22615441
TI  - Stopcock contamination: the source does not explain it all.

PMID- 22615442
TI  - Back to the future: anesthesiology style with courage!

PMID- 22615443
TI  - Blood pressure and adverse perioperative neurologic outcomes: an uncomfortable
      position.

PMID- 22615444
TI  - Caveat lector.

PMID- 22615445
TI  - Pediatric anesthesia safety: then and now.

PMID- 22615446
TI  - Pulmonary artery catheter in cardiac surgery revisited.

PMID- 22615447
TI  - An additional consideration when reviewing the effect of pulmonary artery
      catheters in cardiac surgery performed prior to 2007.

PMID- 22615448
TI  - Not Boyle's Law.

PMID- 22615450
TI  - Development of an Fc-enhanced anti-B7-H3 monoclonal antibody with potent
      antitumor activity.
AB  - PURPOSE: The goal of this research was to harness a monoclonal antibody (mAb)
      discovery platform to identify cell-surface antigens highly expressed on cancer
      and develop, through Fc optimization, potent mAb therapies toward these tumor
      specific antigens. EXPERIMENTAL DESIGN: Fifty independent mAbs targeting the cell
      surface immunoregulatory B7-H3 protein were obtained through independent intact
      cell-based immunizations using human tissue progenitor cells, cancer cell lines,
      or cell lines displaying cancer stem cell properties. Binding studies revealed
      this natively reactive B7-H3 mAb panel to bind a range of independent B7-H3
      epitopes. Immunohistochemical analyses showed that a subset displayed strong
      reactivity to a broad range of human cancers while exhibiting limited binding to
      normal human tissues. A B7-H3 mAb displaying exquisite tumor/normal differential
      binding was selected for humanization and incorporation of an Fc domain modified
      to enhance effector-mediated antitumor function via increased affinity for the
      activating receptor CD16A and decreased binding to the inhibitory receptor CD32B.
      RESULTS: MGA271, the resulting engineered anti-B7-H3 mAb, mediates potent
      antibody-dependent cellular cytotoxicity against a broad range of tumor cell
      types. Furthermore, in human CD16A-bearing transgenic mice, MGA271 exhibited
      potent antitumor activity in B7-H3-expressing xenograft models of renal cell and
      bladder carcinoma. Toxicology studies carried out in cynomolgus monkeys revealed
      no significant test article-related safety findings. CONCLUSIONS: This data
      supports evaluation of MGA271 clinical utility in B7-H3-expressing cancer, while
      validating a combination of a nontarget biased approach of intact cell
      immunizations and immunohistochemistry to identify novel cancer antigens with Fc
      based mAb engineering to enable potent antitumor activity.

PMID- 22615451
TI  - Molecular pathways: interferon/stat1 pathway: role in the tumor resistance to
      genotoxic stress and aggressive growth.
AB  - STAT1 is activated by IFNs and other cell signals. Following activation, STAT1 is
      translocated to the nuclei and activates transcription of IFN-stimulated genes.
      Although the activation of STAT1 by IFNs is classically associated with antiviral
      defense and tumor-suppressive functions, emerging data indicate that expression
      of the STAT1 pathway confers cellular resistance to DNA-damaging agents and
      mediates aggressive tumor growth. Recent advances in the development of Janus
      activated kinase/Stat inhibitors and peptide inhibitors specific for individual
      Stat proteins may provide new insights into the controversial functions of this
      pathway.

PMID- 22615456
TI  - Tocilizumab in patients with active rheumatoid arthritis and inadequate responses
      to DMARDs and/or TNF inhibitors: a large, open-label study close to clinical
      practice.
AB  - OBJECTIVE: To evaluate the safety and efficacy of tocilizumab in clinical
      practice in patients with rheumatoid arthritis (RA) with inadequate responses
      (IR) to disease-modifying antirheumatic drugs (DMARDs) or both DMARDs and tumour
      necrosis factor alpha inhibitors (TNFis). METHODS: Patients-categorised as TNFi
      naive, TNFi-previous (washout) or TNFi-recent (no washout) -received open-label
      tocilizumab (8 mg/kg) every 4 weeks +/- DMARDs for 24 weeks. Adverse events (AEs)
      and treatment discontinuations were monitored. Efficacy end points included
      American College of Rheumatology (ACR) responses, 28-joint disease activity score
      (DAS28) and European League Against Rheumatism responses. RESULTS: Overall, 1681
      (976 TNF-naive, 298 TNFi-previous and 407 TNFi-recent) patients were treated;
      5.1% discontinued treatment because of AEs. The AE rate was numerically higher in
      TNFi-recent (652.6/100 patient-years (PY)) and TNFi-previous (653.6/100PY) than
      in TNFi-naive (551.1/100PY) patients. Serious AE rates were 18.0/100PY,
      28.0/100PY and 18.6/100PY; serious infection rates were 6.0/100PY, 6.8/100PY and
      4.2/100PY, respectively. At week 4, 36.5% of patients achieved ACR20 response and
      14.9% DAS28 remission (<2.6); at week 24, 66.9%, 46.6%, 26.4% and 56.8% achieved
      ACR20/ACR50/ACR70 responses and DAS28 remission, respectively. Overall, 61.6%
      (TNFi-naive), 48.5% (TNFi-previous) and 50.4% (TNFi-recent) patients achieved
      DAS28 remission. CONCLUSIONS: In patients with RA who were DMARD-IR/TNFi-IR,
      tocilizumab +/- DMARDs provided rapid and sustained efficacy without unexpected
      safety concerns.

PMID- 22615457
TI  - Genetic contribution to radiographic severity in osteoarthritis of the knee.
AB  - OBJECTIVE: Knee osteoarthritis (OA) has a significant genetic component. The
      authors have assessed the role of three variants reported to influence risk of
      knee OA with p<5*10-8 in determining patellofemoral and tibiofemoral Kellgren
      Lawrence (K/L) grade in knee OA cases. METHODS: 3474 knee OA cases with sky-line
      and weight-bearing antero-posterior x-rays of the knee were selected based on the
      presentation of K/L grade >=2 at either the tibiofemoral or patellofemoral
      compartments for one or both knees. Patients belonging to three UK cohorts, were
      genotyped for rs143383, rs4730250 and rs11842874 mapping to the GDF5, COG5 and
      MCF2L genes, respectively. The association between tibiofemoral K/L grade and
      patellofemoral K/L grade was assessed after adjusting for age, gender and body
      mass index. RESULTS: No significant association was found between the rs4730250
      and radiographic severity. The rs11842874 mapping to MCF2L was found to be
      nominally significantly associated with patellofemoral K/L grade as a
      quantitative trait (p=0.027) but not as a binary trait. The GDF5 single
      nucleotide polymorphism rs143383 was associated with tibiofemoral K/L grade
      (beta=0.05 (95% CI 0.02 to 0.08) p=0.0011). CONCLUSIONS: Our data indicate that
      within individuals affected by radiographic knee OA, OAGDF5 has a modest but
      significant effect on radiographic severity after adjustment for the major risk
      factors.

PMID- 22615459
TI  - Persistence of immunoglobulin-producing cells in parotid salivary glands of
      patients with primary Sjogren's syndrome after B cell depletion therapy.
AB  - OBJECTIVES: To assess the persistence of immunoglobulin-producing cell
      populations in the parotid salivary glands of patients with primary Sjogren's
      syndrome (pSS) after B cell depletion therapy with rituximab. METHODS: Thirteen
      patients with pSS and four control patients were included in this study. Patients
      with pSS were treated with rituximab or placebo. Sequence analysis was carried
      out on IgA- and IgG-encoding transcripts extracted from parotid salivary gland
      biopsy specimens taken before treatment and at 12-16 and 36-52 weeks after
      treatment. RESULTS: At baseline, many clonally related sequences were seen in
      patients with pSS. The number of clonal expansions was significantly higher in
      patients with pSS than in control patients. Clonal expansions were composed of
      IgA- and/or IgG-expressing cells. Rituximab did not significantly alter the
      degree of clonal expansions. Groups of clonally related cells had members which
      were shared between biopsy specimens taken before and after treatment. Mutation
      frequencies of immunoglobulin sequences from clonally related cells in patients
      with pSS were higher after treatment. CONCLUSIONS: Rituximab treatment does not
      alter the characteristic features of increased clonal expansions seen in the
      parotid salivary glands of patients with pSS. The presence of clonally related
      immunoglobulin-producing cells before and after rituximab treatment strongly
      suggests that immunoglobulin-producing cells persist in salivary glands of
      patients with pSS despite B cell depletion. The presence of mixed isotype
      expression within groups of clonally related cells indicates local class
      switching in salivary glands of patients with pSS. Persistent immunoglobulin
      producing cells may underlie disease relapse after treatment.

PMID- 22615458
TI  - Positivity for anti-cyclic citrullinated peptide is associated with a better
      response to abatacept: data from the 'Orencia and Rheumatoid Arthritis' registry.
AB  - OBJECTIVES: Very limited data are available regarding the efficacy of abatacept
      (ABA) in real life. The aims of this study were to determine the efficacy of ABA
      in rheumatoid arthritis and predicting factors of efficacy in common practice.
      METHODS: The Orencia and Rheumatoid Arthritis" (ORA) prospective registry,
      promoted by the French Society of Rheumatology, has included 1003 patients with
      RA. RESULTS: 773 patients had already fulfilled the 6-month follow-up visit. Only
      21.3% of patients would have fulfilled inclusion criteria used in pivotal
      controlled trials. The European League Against Rheumatism (EULAR) response, was
      observed in 330 (59.1%) of the 558 assessed patients (good response: 20.4%,
      moderate response: 38.7%) and was similar in patients who did and in patients who
      did not fulfill inclusion criteria of controlled trials. Among EULAR responders,
      initial 28-joint disease activity score (5.4 (4.7-6.5) in responders vs 4.9 (4.0
      6.0) in non responders, p< 0.0001), the proportion of rheumatoid factor (75.6% vs
      66.7%, p= 0.03) and the proportion of anti-cyclic citrullinated peptide antibody
      (anti-CCP)-positivity (75.9% vs 62.2%, p= 0.001) were significantly higher. In
      multivariate analysis adjusted on initial 28-joint disease activity score and
      CRP, anti-CCP positivity was associated with EULAR response (OR=1.9;95% CI=1.2 to
      2.9, p=0.007), but not rheumatoid factor (OR=1.0;95% CI=0.6 to 1.6, p=0.9). Anti
      CCP positivity was also significantly associated with a higher ABA retention rate
      at 6 months. CONCLUSIONS: Real life efficacy of ABA in the ORA registry was
      similar as that reported in clinical trials. Anti-CCP positivity was associated
      with a better response to ABA, independently from disease activity.

PMID- 22615461
TI  - Beyond crystals: the dialectic of materials and information.
AB  - We argue for a convergence of crystallography, materials science and biology,
      that will come about through asking materials questions about biology and
      biological questions about materials, illuminated by considerations of
      information. The complex structures now being studied in biology and produced in
      nanotechnology have outstripped the framework of classical crystallography, and a
      variety of organizing concepts are now taking shape into a more modern and
      dynamic science of structure, form and function. Absolute stability and
      equilibrium are replaced by metastable structures existing in a flux of energy
      carrying information and moving within an energy landscape of complex topology.
      Structures give place to processes and processes to systems. The fundamental
      level is that of atoms. As smaller and smaller groups of atoms are used for their
      physical properties, quantum effects become important; already we see quantum
      computation taking shape. Concepts move towards those in life with the emergence
      of specifically informational structures. We now see the possibility of the
      artificial construction of a synthetic living system, different from biological
      life, but having many or all of the same properties. Interactions are essentially
      nonlinear and collective. Structures begin to have an evolutionary history with
      episodes of symbiosis. Underlying all the structures are constraints of time and
      space. Through hierarchization, a more general principle than the periodicity of
      crystals, structures may be found within structures on different scales. We must
      integrate unifying concepts from dynamical systems and information theory to form
      a coherent language and science of shape and structure beyond crystals. To this
      end, we discuss the idea of categorizing structures based on information
      according to the algorithmic complexity of their assembly.

PMID- 22615463
TI  - Using shape for self-assembly.
AB  - A 1980 poem by Alan Mackay outlines his aspiration 'to see what all have seen but
      think what none have thought': a daunting task, which he accomplished not once,
      but several times. A 'truly myriadminded, manysided man-a veritable
      triacontahedron' in the words of his colleagues and friends, Alan Mackay pursued
      a lifelong interest in the problems of morphogenesis and form, a comprehension of
      which necessitated him crisscrossing the borders of the inanimate and animate
      world of soft and hard materials, through the integration of concepts and methods
      of chemistry, physics, mathematics and biology. In other words, he realized in
      his time a genuinely interdisciplinary approach to complex problems that still to
      this day remains beyond much of the academic community. Being invited to
      contribute a paper on the theme 'beyond crystals', we naturally wondered how Alan
      Mackay would think about the world of nanoscale self-assembly where so much
      depends on shape and form.

PMID- 22615464
TI  - Tubular precipitation structures: materials synthesis under non-equilibrium
      conditions.
AB  - Inorganic precipitation reactions are known to self-organize a variety of
      macroscopic structures, including hollow tubes. We discuss recent advances in
      this field with an emphasis on experiments similar to 'silica gardens'. These
      reactions involve metal salts and sodium silicate solution. Reactions triggered
      from reagent-loaded microbeads can produce tubes with inner radii of down to 3
      MUm. Distinct wall morphologies are reported. For pump-driven injection, three
      qualitatively different growth regimes exist. In one of these regimes, tubes
      assemble around a buoyant jet of reactant solution, which allows the quantitative
      prediction of the tube radius. Additional topics include relaxation oscillations
      and the templating of tube growth with pinned gas bubble and mechanical devices.
      The tube materials and their nano-to-micro architectures are discussed for the
      cases of silica/Cu(OH)(2) and silica/Zn(OH)(2)/ZnO tubes. The latter case shows
      photocatalytic activity and photoluminescence.

PMID- 22615465
TI  - Crystal growth as an excitable medium.
AB  - Crystal growth has been widely studied for many years, and, since the pioneering
      work of Burton, Cabrera and Frank, spirals and target patterns on the crystal
      surface have been understood as forms of tangential crystal growth mediated by
      defects and by two-dimensional nucleation. Similar spirals and target patterns
      are ubiquitous in physical systems describable as excitable media. Here, we
      demonstrate that this is not merely a superficial resemblance, that the physics
      of crystal growth can be set within the framework of an excitable medium, and
      that appreciating this correspondence may prove useful to both fields. Apart from
      solid crystals, we discuss how our model applies to the biomaterial nacre, formed
      by layer growth of a biological liquid crystal.

PMID- 22615466
TI  - Decoding the energy landscape: extracting structure, dynamics and thermodynamics.
AB  - Describing a potential energy surface in terms of local minima and the transition
      states that connect them provides a conceptual and computational framework for
      understanding and predicting observable properties. Visualizing the potential
      energy landscape using disconnectivity graphs supplies a graphical connection
      between different structure-seeking systems, which can relax efficiently to a
      particular morphology. Landscapes involving competing morphologies support
      multiple potential energy funnels, which may exhibit characteristic heat capacity
      features and relaxation time scales. These connections between the organization
      of the potential energy landscape and structure, dynamics and thermodynamics are
      common to all the examples presented, ranging from atomic and molecular clusters
      to biomolecules and soft and condensed matter. Further connections between motifs
      in the energy landscape and the interparticle forces can be developed using
      symmetry considerations and results from catastrophe theory.

PMID- 22615467
TI  - Unusual co-crystal of isonicotinamide: the structural landscape in crystal
      engineering.
AB  - The idea of a structural landscape is based on the fact that a large number of
      crystal structures can be associated with a particular organic molecule. Taken
      together, all these structures constitute the landscape. The landscape includes
      polymorphs, pseudopolymorphs and solvates. Under certain circumstances, it may
      also include multi-component crystals (or co-crystals) that contain the reference
      molecule as one of the components. Under still other circumstances, the landscape
      may include the crystal structures of molecules that are closely related to the
      reference molecule. The idea of a landscape is to facilitate the understanding of
      the process of crystallization. It includes all minima that can, in principle, be
      accessed by the molecule in question as it traverses the path from solution to
      the crystal. Isonicotinamide is a molecule that is known to form many co
      crystals. We report here a 2:1 co-crystal of this amide with 3,5-dinitrobenzoic
      acid, wherein an unusual N-H...N hydrogen-bonded pattern is observed. This
      crystal structure offers some hints about the recognition processes between
      molecules that might be implicated during crystallization. Also included is a
      review of other recent results that illustrate the concept of the structural
      landscape.

PMID- 22615460
TI  - Update on the profile of the EUSTAR cohort: an analysis of the EULAR Scleroderma
      Trials and Research group database.
AB  - OBJECTIVES: Systemic sclerosis (SSc) is a rare disease requiring multicentre
      collaboration to reveal comprehensive details of disease-related causes for
      morbidity and mortality. METHODS: The European League Against Rheumatism (EULAR)
      Scleroderma Trials and Research (EUSTAR) group initiated a database to
      prospectively gather key data of patients with SSc using a minimal essential
      dataset that was reorganised in 2008 introducing new items. Baseline visit data
      of patients who were registered between 2004 and 2011 were analysed using
      descriptive statistics. RESULTS: In June 2011, 7655 patients (2838 with diffuse
      cutaneous (dc) and 4481 with limited cutaneous (lc) SSc who fulfilled the
      American College of Rheumatology diagnostic criteria had been registered in 174
      centres, mainly European. The most prominent hallmarks of disease were Raynaud's
      phenomenon (96.3%), antinuclear antibodies (93.4%) and a typical capillaroscopic
      pattern (90.9%). Scleroderma was more common on fingers and hands than on any
      other part of the skin. Proton pump inhibitors (65.2%), calcium channel blockers
      (52.7%), and corticosteroids (45.3%) were most often prescribed. Among the
      immunosuppressant agents, cyclophosphamide was used more often in dcSSc than in
      lcSSc. CONCLUSIONS: The EUSTAR database provides an abundance of information on
      the true clinical face of SSc that will be helpful in improving the
      classification of SSc and its subsets and for developing more specific
      therapeutic recommendations.

PMID- 22615468
TI  - A glimpse of quantum phenomena in optical lattices.
AB  - Optical lattices in cold atomic systems offer an excellent setting for realizing
      quantum condensed matter phenomena. Here, a glimpse of such a setting is provided
      for the non-specialist. Some basic aspects of cold atomic gases and optical
      lattices are reviewed. Quantum many-body physics is explored in the case of
      interacting bosons on a lattice. Quantum behaviour in the presence of a potential
      landscape is examined for three different cases: a hexagonal lattice potential, a
      quasi-periodic potential and a disorder potential.

PMID- 22615469
TI  - The memory of surfaces: epitaxial growth on quasi-crystals.
AB  - If crystal structures can be viewed as repositories of information, then crystal
      surfaces offer a pathway by which this information can be used to grow new
      structures through the process of epitaxy. The information transfer process is
      one of self-organization, and the kinetic and energetic factors influencing this
      are complex. They include the relative strengths of the adsorbate-adsorbate and
      adsorbate-substrate interactions, the flux of incoming species and the
      temperature of the system. In this brief review, we explore how the interplay of
      these factors influences the degree to which the epitaxial structures retain the
      'memory' of the template, illustrating the discussion with examples from epitaxy
      on quasi-crystal surfaces.

PMID- 22615470
TI  - Structures of pseudo-decagonal approximants in Al-Co-Ni.
AB  - Quasi-crystals shocked the crystallographic world when they were reported in
      1984. We now know that they are not a rare exception, and can be found in many
      alloy systems. One of the richer systems for quasi-crystals and their
      approximants is Al-Co-Ni. A large series of pseudo-decagonal (PD) approximants
      have been found. Only two of them, PD4 and PD8, have been solved by X-ray
      crystallography. We report here the structures of PD1, PD2, PD3 and PD5, solved
      from the limited information that is provided by electron diffraction patterns,
      unit cell dimensions and high-resolution electron microscopy images.

PMID- 22615471
TI  - DNA information: from digital code to analogue structure.
AB  - The digital linear coding carried by the base pairs in the DNA double helix is
      now known to have an important component that acts by altering, along its length,
      the natural shape and stiffness of the molecule. In this way, one region of DNA
      is structurally distinguished from another, constituting an additional form of
      encoded information manifest in three-dimensional space. These shape and
      stiffness variations help in guiding and facilitating the DNA during its three
      dimensional spatial interactions. Such interactions with itself allow
      communication between genes and enhanced wrapping and histone-octamer binding
      within the nucleosome core particle. Meanwhile, interactions with proteins can
      have a reduced entropic binding penalty owing to advantageous sequence-dependent
      bending anisotropy. Sequence periodicity within the DNA, giving a corresponding
      structural periodicity of shape and stiffness, also influences the supercoiling
      of the molecule, which, in turn, plays an important facilitating role. In effect,
      the super-helical density acts as an analogue regulatory mode in contrast to the
      more commonly acknowledged purely digital mode. Many of these ideas are still
      poorly understood, and represent a fundamental and outstanding biological
      question. This review gives an overview of very recent developments, and
      hopefully identifies promising future lines of enquiry.

PMID- 22615472
TI  - DNA, dichotomic classes and frame synchronization: a quasi-crystal framework.
AB  - In this article, we show how a new mathematical model of the genetic code can be
      exploited for investigating the almost periodic properties of DNA and mRNA
      protein-coding sequences. We present the main mathematical features of the model
      and highlight its connections with both number theory and group theory. The group
      theoretic framework presents interesting analogies with the theory of crystals.
      Moreover, we exploit the information provided by dichotomic classes, binary
      variables naturally derived from the mathematical model, in order to build
      statistical classifiers for retrieving and predicting the normal reading frame
      used by the ribosome in protein synthesis. The results show that coding sequences
      possess a local informational structure that can be related to frame
      synchronization processes. The information for retrieving the normal reading
      frame, which implies the existence of short-range correlations and almost
      periodic structures related to the organization of codons, offers an interesting
      analogy with the properties of quasi-crystals. From a theoretical point of view,
      our results might contribute to clarifying the relation between biological
      information and shape in nucleic acids and proteins. Also, from the point of view
      of applications, we present new promising tools for designing efficient
      algorithms for frame synchronization, which plays a crucial role in faithful
      synthesis of proteins.

PMID- 22615473
TI  - Peptide and RNA contributions to iron-sulphur chemical gardens as life's first
      inorganic compartments, catalysts, capacitors and condensers.
AB  - Hydrothermal chimneys and compartments comprising transition metal sulphides and
      associated minerals have been proposed as likely locations for the beginnings of
      life. In laboratory simulations of off-axis alkaline springs, it is shown that
      the interaction of a simulated alkaline sulphide-bearing submarine vent solution
      with a primeval anoxic iron-bearing ocean leads to the formation of chimney
      structures reminiscent of chemical gardens. These chimneys display periodicity in
      their deposition and exhibit diverse morphologies and mineralogies, affording the
      possibilities of catalysis and molecular sequestration. The addition of peptides
      and RNA to the alkaline solution modifies the elemental stoichiometry of the
      chimneys-perhaps indicating the very initial stage of the organic takeover on the
      way to living cells by charged organic polymers potentially synthesized in this
      same environment.

PMID- 22615474
TI  - Spatial and temporal organization of multi-protein assemblies: achieving
      sensitive control in information-rich cell-regulatory systems.
AB  - The regulation of cellular processes in living organisms requires signalling
      systems that have a high signal-to-noise ratio. This is usually achieved by
      transient, multi-protein complexes that assemble cooperatively. Even in the
      crowded environment of the cell, such assemblies are unlikely to form by chance,
      thereby providing a sensitive regulation of cellular processes. Furthermore,
      selectivity and sensitivity may be achieved by the requirement for concerted
      folding and binding of previously unfolded components. We illustrate these
      features by focusing on two essential signalling pathways of eukaryotic cells:
      first, the monitoring and repair of DNA damage by non-homologous end joining, and
      second, the mitotic spindle assembly checkpoint, which detects and corrects
      defective attachments of chromosomes to the kinetochore. We show that multi
      protein assemblies moderate the full range of functional complexity and diversity
      in the two signalling systems. Deciphering the nature of the interactions is
      central to understanding the mechanisms that control the flow of information in
      cell signalling and regulation.

PMID- 22615475
TI  - Perceptual acclimatization post nonlinear frequency compression hearing aid
      fitting in older children.
AB  - PURPOSE: In this study, the authors evaluated the effect of frequency compression
      hearing aids on speech perception ability and the time course and magnitude of
      acclimatization-related changes. METHOD: Participants included children ages 11
      18 years. Speech perception ability was evaluated over well-controlled baseline,
      treatment, and withdrawal study phases. Study-worn hearing aids were individually
      fitted to all participants. The authors evaluated speech perception ability using
      outcomes of speech detection (/s/ and /[symbol in text]/ sounds), /s-[symbol in
      text]/ discrimination, and plural and consonant recognition. RESULTS: Indices of
      change were discussed on a case-by-case basis across all study phases.
      Significant treatment effects were measured for all cases, on at least one
      measure, with some listeners displaying significant acclimatization trends
      following a trial of frequency compression. CONCLUSION: Findings suggest that
      frequency compression provided varying outcomes, both in benefit and
      acclimatization, across listeners. For some, a period of acclimatization was
      necessary before change could be measured. For others, performance remained
      stable over the time course under evaluation, suggesting that some but not all
      children will experience improved speech recognition ability after a period of
      frequency compression hearing aid use.

PMID- 22615476
TI  - Spatiotemporal coupling of the tongue in amyotrophic lateral sclerosis.
AB  - PURPOSE: The primary aim of the investigation was to identify deficits in
      spatiotemporal coupling between tongue regions in amyotrophic lateral sclerosis
      (ALS). The relations between disease-related changes in tongue movement patterns
      and speech intelligibility were also determined.  Methods The authors recorded
      word productions from 11 individuals with ALS with mild, moderate, and severe
      dysarthria using an x-ray microbeam during word productions. A coupling index
      based on sliding window covariance was used to determine disease-related changes
      in the coupling between the tongue regions across each word. RESULTS: The results
      indicated decreased spatiotemporal coupling of mid-posterior tongue regions and
      reduced tongue speed in the ALS-moderate subgroup. Changes in the range of tongue
      coupling relations and speed of movement were highly correlated with speech
      intelligibility. CONCLUSIONS: These results provide new insights into the loss of
      lingual motor control due to ALS and suggest that measures of tongue performance
      may provide useful indicators of bulbar disease severity and progression.

PMID- 22615477
TI  - The relationship between perception of vocal effort and relative fundamental
      frequency during voicing offset and onset.
AB  - PURPOSE: In this study, the authors aimed to determine the relationship between
      relative fundamental frequency (RFF) and listener perception of vocal effort in
      individuals with varying degrees of vocal hyperfunction. METHOD: Thirty women
      diagnosed with voice disorders commonly associated with vocal hyperfunction and
      10 healthy women provided speech samples that were used to obtain parameters of
      RFF. Twelve listeners judged the speech samples for overall severity and vocal
      effort (VE) using rating scales. RESULTS: Significant but relatively weak
      negative correlations were found between perceptual measures and offset RFF
      parameters. Although offset RFF was increased in healthy participants relative to
      speakers with voice disorders, no differences were seen in RFF as a function of
      severity of VE in individuals with voice disorders. CONCLUSIONS: Although a
      statistically significant correlation between offset RFF and VE was found,
      examination of data as a function of both VE and health status indicated that RFF
      more accurately classifies the presence of a voice disorder than does severity of
      voice quality or VE. There is a need for further research to investigate the
      clinical utility of RFF measures for assessment of rehabilitation progress.

PMID- 22615478
TI  - A population study of children's acquisition of Hong Kong Cantonese consonants,
      vowels, and tones.
AB  - PURPOSE: This study investigated children's acquisition of Hong Kong Cantonese.
      METHOD: Participants were 1,726 children ages 2;4 to 12;4 (years;months). Single
      word speech samples were collected to examine 4 measures: initial consonants,
      final consonants, vowels/diphthongs, and lexical tones. A 2-way analysis of
      variance was performed to examine the effects of age and sex on phoneme
      acquisition. RESULTS: There was rapid acquisition of initial consonants from age
      2;6 to age 4;6. All 19 initial consonants were acquired by age 6;0 (90%
      criterion): /p-/, /m-/, and /j-/ were acquired the earliest; the last were /ts(h)
      / and /s-/. Final consonants had a different acquisition time from their initial
      counterparts. Vowels were acquired by age 5;0 and diphthongs by age 4;0. All 9
      tones were acquired by age 2;6. The main effect of age was significant for all 4
      measures, whereas sex was significant for all measures except tone. Common
      phonological patterns (>= 10%) for initial consonants were stopping, fronting,
      deaspiration, delabialization, affrication, and nasalization; patterns with 5.0%
      9.9% occurrence were backing, deaffrication, gliding, and dentalization.
      CONCLUSIONS: The acquisition of Cantonese showed similarities with English
      acquisition yet also had specific characteristics. Factors that contributed to
      the acquisition rate were functional load, articulatory ease, consonant-vowel
      interactions, phonetic variations, and the behavior of vowels and their
      allophones.

PMID- 22615479
TI  - The influence of reduced audible bandwidth on asynchronous double-vowel
      identification.
AB  - PURPOSE: In this study, the authors sought to determine whether reduced audible
      bandwidth associated with hearing loss contributes to difficulty benefiting from
      an onset asynchrony between sounds. METHOD: Synthetic double-vowel identification
      was measured for normal-hearing listeners and listeners with hearing loss. One
      vowel (Target 2) was 250 ms in duration, and one (Target 1) varied in duration.
      The vowels had the same offset, and an onset asynchrony between the vowels ranged
      between 0 and 200 ms. Listeners identified both vowels in their perceived order.
      The scoring metrics used were as follows: Target 1 correctly identified in the
      correct position, Target 2 correctly identified in the correct position, ordered
      double-vowel identification, and unordered double-vowel identification. The same
      experiment was conducted with vowels low-pass filtered at 900 Hz simulating
      reduced audible bandwidth. RESULTS: For all scoring metrics, increases in onset
      asynchrony led to better vowel identification. Listeners with hearing loss
      benefited less from onset asynchrony than normal-hearing listeners only for
      Target 2 identification. Filtering the vowels reduced onset asynchrony benefit
      for all scoring categories and for both groups. CONCLUSION: Results implicate
      reduced audible bandwidth in difficulties of listeners when using onset
      asynchrony for sound segregation. Therefore, listeners with a reduced audible
      bandwidth may have communication difficulties in natural environments.

PMID- 22615481
TI  - Post-training unilateral amygdala lesions selectively impair contextual fear
      memories.
AB  - The basolateral amygdala (BLA) and the dorsal hippocampus (dHPC) are both
      structures with key roles in contextual fear conditioning. During fear
      conditioning, it is postulated that contextual representations of the environment
      are formed in the hippocampus, which are then associated with foot shock in the
      amygdala. However, it is not known to what extent a functional connection between
      these two structures is required. This study investigated the effect on
      contextual and cued fear conditioning of disconnecting the BLA and dHPC, using
      asymmetrically placed, excitotoxic unilateral lesions. Post-training lesions
      selectively impaired contextual, but not cued, fear, while pretraining lesions
      resulted in a similar but nonsignificant pattern of results. This effect was
      unexpectedly observed in both the contralateral disconnection group and the
      anticipated ipsilateral control, which prompted further examination of individual
      unilateral lesions of BLA and dHPC. Post-training unilateral dHPC lesions had no
      effect on contextual fear memories while bilateral dHPC lesions and unilateral
      BLA lesions resulted in a near total abolition of contextual fear but not cued
      conditioned fear. Again, pretraining unilateral BLA lesions resulted in a strong
      but nonsignificant trend to the impairment of contextual fear. Furthermore, an
      analysis of context test-induced Fos protein expression in the BLA contralateral
      to the lesion site revealed no differences between post-training SHAM and
      unilateral BLA lesioned animals. Therefore, post-training unilateral lesions of
      the BLA are sufficient to severely impair contextual, but not cued, fear
      memories.

PMID- 22615482
TI  - Can Rowland Universal Dementia Assessment Scale (RUDAS) replace Mini-mental State
      Examination (MMSE) for dementia screening in a Thai geriatric outpatient setting?
AB  - Mini-mental-State Examination (MMSE) is a widely used tool for dementia
      screening. However, several limitations are found and the Rowland Universal
      Dementia Assessment Scale (RUDAS) appears to be an alternative test. The
      objective in this study was to compare the performance of MMSE-Thai 2002 and
      RUDAS-Thai for dementia screening, and to determine their performances and
      identify their optimal cut-off points. The participants were older patients from
      a Geriatric and Neurology Outpatient Clinic, Srinagarind Hospital, Khon Kaen
      University. The RUDAS-Thai and the MMSE-Thai 2002 were administered to each
      participant. Subsequently, a specialist physician assessed each participant for
      dementia. Results showed the area under receiver operating characteristic curve
      for both RUDAS-Thai (81.0%; 95%CI, 74.8-87.2) and MMSE-Thai 2002 (81.2%; 95%CI,
      74.9-87.4) were equal. A score of 24 or lower provided an optimal cut-off point.
      Our finding supports that the RUDAS-Thai can be an effective alternative test for
      dementia screening. For both test scores, a score of 24 or lower is an optimal
      cut-off point to provide an indication of developing dementia.

PMID- 22615480
TI  - The effect of interference on temporal order memory for random and fixed
      sequences in nondemented older adults.
AB  - Two experiments tested the effect of temporal interference on order memory for
      fixed and random sequences in young adults and nondemented older adults. The
      results demonstrate that temporal order memory for fixed and random sequences is
      impaired in nondemented older adults, particularly when temporal interference is
      high. However, temporal order memory for fixed sequences is comparable between
      older adults and young adults when temporal interference is minimized. The
      results suggest that temporal order memory is less efficient and more susceptible
      to interference in older adults, possibly due to impaired temporal pattern
      separation.

PMID- 22615483
TI  - Fifty percent reduced-dose cerebral CT perfusion imaging of Alzheimer's disease:
      regional blood flow abnormalities.
AB  - To evaluate the value of 50% reduced-dose cerebral computed tomography
      (CT)perfusion imaging (CTPI) to show the perfusion abnormalities in Alzheimer's
      disease (AD), as an attempt to develop a new imaging protocol with lower
      radiation dose to track the correlation of AD with regional blood flow
      abnormalities. A total of 52 patients with AD were assigned to the AD group and
      28 healthy volunteers served as the control group. All participants were given a
      50% reduced-dose cerebral CTPI (current was reduced from 160 to 80 mA) test by a
      multislice spiral CT scanner. Perfusion parameters of the bilateral frontal
      cortex, temporal cortex, hippocampus, and basal ganglia were measured, including
      the cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time
      (MTT), and time to peak (TTP). Both the CBV and CBF values of the measured
      regions were significantly higher in the healthy control group than in the AD
      group (P < .05), while the MTT and TTP values of these cerebral areas were
      significantly lower in the healthy control group than in the AD group (P < .05).
      Four perfusion parameters, namely the MTT of the left frontal cortex, right
      temporal cortex, right basal ganglia, and right hippocampus, had the greatest
      sensitivity and a striking correlation with the incidence of AD. The blood flow
      per unit of time in the regions of interest was significantly lower in the AD
      group, which provides new evidence for the existence of microcirculation
      disturbance and ischemia in AD. The 50% reduced-dose cerebral CTPI scan is
      valuable to show the regional perfusion abnormalities in the patients with AD.

PMID- 22615484
TI  - "The brain is such a delicate thing": an exploration of fear and seizures among
      young people with epilepsy.
AB  - Epilepsy is a condition where pathology, diverse manifestations and attached
      social understandings contribute to an emotional experience unlike many other
      chronic conditions. The emotional dimension to epilepsy has been little
      considered in existing research. OBJECTIVES: To explore the emotional experience
      of young people with epilepsy. METHODS: A qualitative study involving in-depth
      interviews with 37 young people diagnosed with epilepsy. RESULTS: Fear emerged as
      the key emotion and this largely related to the experience, or anticipated
      experience, of seizure activity. Three key features of fear and epilepsy emerged
      through the analysis; harm, temporality and action. The fear experienced was not
      only external, relating to immediate injury, but also internal in terms of
      potential damage to the brain. The embodied nature of epilepsy can, therefore,
      present a threat to conceptions of the self. Underlying this internal dimension
      of fear is an understanding of the brain as central to the sense of self.
      CONCLUSIONS: The experience of epilepsy does not only involve fear of physical
      harm but also fear of a loss of self. We conclude that there are broader
      (alternative) readings of the experience of epilepsy that are often overlooked.

PMID- 22615485
TI  - Late presentation of neonatal omphalitis following dry cord care.

PMID- 22615486
TI  - Assessing the feasibility of a Web-based self-management program for adolescents
      with migraines and their caregivers.

PMID- 22615487
TI  - Fever for 14 weeks.

PMID- 22615488
TI  - KDM3B is the H3K9 demethylase involved in transcriptional activation of lmo2 in
      leukemia.
AB  - Histone lysine methylation and demethylation are considered critical steps in
      transcriptional regulation. In this report, we performed chromatin
      immunoprecipitation with microarray technology (ChIP-chip) analysis to examine
      the genome-wide occupancy of H3K9-me2 during all-trans-retinoic acid (ATRA)
      induced differentiation of HL-60 promyelocytic leukemia cells. Using this
      approach, we found that KDM3B, which contains a JmjC domain, was downregulated
      during differentiation through the recruitment of a corepressor complex.
      Furthermore, KDM3B displayed histone H3K9-me1/2 demethylase activity and induced
      leukemogenic oncogene lmo2 expression via a synergistic interaction with CBP.
      Here, we found that KDM3B repressed leukemia cell differentiation and was
      upregulated in blood cells from acute lymphoblastic leukemia (ALL)-type leukemia
      patients. The combined results of this study provide evidence that the H3K9-me1/2
      demethylase KDM3B might play a role in leukemogenesis via activation of lmo2
      through interdependent actions with the histone acetyltransferase (HAT) complex
      containing CBP.

PMID- 22615489
TI  - Transforming growth factor beta inhibits bone morphogenetic protein-induced
      transcription through novel phosphorylated Smad1/5-Smad3 complexes.
AB  - In vivo cells receive simultaneous signals from multiple extracellular ligands
      and must integrate and interpret them to respond appropriately. Here we
      investigate the interplay between pathways downstream of two transforming growth
      factor beta (TGF-beta) superfamily members, bone morphogenetic protein (BMP) and
      TGF-beta. We show that in multiple cell lines, TGF-beta potently inhibits BMP
      induced transcription at the level of both BMP-responsive reporter genes and
      endogenous BMP target genes. This inhibitory effect requires the TGF-beta type I
      receptor ALK5 and is independent of new protein synthesis. Strikingly, we show
      that Smad3 is required for TGF-beta's inhibitory effects, whereas Smad2 is not.
      We go on to demonstrate that TGF-beta induces the formation of complexes
      comprising phosphorylated Smad1/5 and Smad3, which bind to BMP-responsive
      elements in vitro and in vivo and mediate TGF-beta-induced transcriptional
      repression. Furthermore, loss of Smad3 confers on TGF-beta the ability to induce
      transcription via BMP-responsive elements. Our results therefore suggest that not
      only is Smad3 important for mediating TGF-beta's inhibitory effects on BMP
      signaling but it also plays a critical role in restricting the transcriptional
      output in response to TGF-beta.

PMID- 22615490
TI  - Phosphorylation of distinct sites in MeCP2 modifies cofactor associations and the
      dynamics of transcriptional regulation.
AB  - Mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2) lead to
      disrupted neuronal function and can cause the neurodevelopmental disorder Rett
      syndrome. MeCP2 is a transcriptional regulator that binds to methylated DNA and
      is most abundant in neuronal nuclei. The mechanisms by which MeCP2 regulates gene
      expression remain ambiguous, as it has been reported to function as a
      transcriptional silencer or activator and to execute these activities through
      both gene-specific and genome-wide mechanisms. We hypothesized that
      posttranslational modifications of MeCP2 may be important for reconciling these
      apparently contradictory functions. Our results demonstrate that MeCP2 contains
      multiple posttranslational modifications, including phosphorylation, acetylation,
      and ubiquitylation. Phosphorylation of MeCP2 at S229 or S80 influenced selective
      in vivo interactions with the chromatin factors HP1 and SMC3 and the cofactors
      Sin3A and YB-1. pS229 MeCP2 was specifically enriched at the RET promoter, and
      phosphorylation of MeCP2 was necessary for differentiation-induced activation and
      repression of the MeCP2 target genes RET and EGR2. These results demonstrate that
      phosphorylation is one of several factors that are important for interpreting the
      complexities of MeCP2 transcriptional modulation.

PMID- 22615491
TI  - Mitogen-activated protein kinase phosphorylation of splicing factor 45 (SPF45)
      regulates SPF45 alternative splicing site utilization, proliferation, and cell
      adhesion.
AB  - The regulation of alternative mRNA splicing factors by extracellular cues and
      signal transduction cascades is poorly understood. Using an engineered
      extracellular signal-regulated kinase 2 (ERK2) that can utilize ATP analogs, we
      have identified the alternative mRNA splicing factor 45 (SPF45), which is
      overexpressed in cancer, as a novel coimmunoprecipitating ERK2 substrate. ERK2
      phosphorylated SPF45 on Thr71 and Ser222 in vitro and in cells in response to H
      RasV12, B-RAF-V600E, and activated MEK1. Jun N-terminal kinase 1 (JNK1) and
      p38alpha also phosphorylated SPF45 in vitro and associated with SPF45 in cells.
      SPF45 was differentially phosphorylated in cells by all three mitogen-activated
      protein (MAP) kinases in response to phorbol myristate acid (PMA), H(2)O(2), UV,
      and anisomycin stimulation. ERK and p38 activation decreased SPF45-dependent exon
      6 exclusion from fas mRNA in a minigene assay in cells. Stable overexpression of
      SPF45 in SKOV-3 cells dramatically inhibited cell proliferation in a
      phosphorylation-dependent manner through inhibition of ErbB2 expression. SPF45
      overexpression also induced EDA inclusion into fibronectin transcripts and
      fibronectin expression in a phosphorylation-dependent and -independent manner,
      respectively, specifically affecting cellular adhesion to a fibronectin matrix.
      These data identify SPF45 as the first splicing factor regulated by multiple MAP
      kinase pathways and show effects of both SPF45 overexpression and
      phosphorylation.

PMID- 22615493
TI  - Cot kinase promotes Ca2+ oscillation/calcineurin-independent osteoclastogenesis
      by stabilizing NFATc1 protein.
AB  - Osteoclasts are multinuclear bone-resorbing cells formed by the fusion of
      monocyte/macrophage-lineage precursor cells. Activation of the transcription
      factor NFATc1 (nuclear factor of activated T cells c1) by the receptor activator
      of NF-kappaB ligand (RANKL) is critical for osteoclast differentiation. In our
      previous report (Y. Kuroda, C. Hisatsune, T. Nakamura, K. Matsuo, and K.
      Mikoshiba. Proc. Natl. Acad. Sci. U. S. A. 105:8643, 2008), we demonstrated that
      osteoblasts induce osteoclast differentiation via Ca(2+) oscillation/calcineurin
      dependent and -independent NFATc1 activation pathways; however, the mechanism
      underlying the latter remained unclear. Here we show that Cot, a serine/threonine
      kinase also known as tumor progression locus 2 (Tpl-2), directly phosphorylates
      all Ca(2+)/calcineurin-regulated NFAT family members (NFATc1 through NFATc4) and
      increases their protein levels. Moreover, Cot activity in osteoclasts was
      enhanced via cell-cell interaction with osteoblasts, and Cot promoted Ca(2+)
      oscillation/calcineurin-independent osteoclastogenesis by increasing NFATc1
      stability through phosphorylation. We propose that NFAT activation in vivo occurs
      via phosphorylation-induced protein stabilization, even in the absence of Ca(2+)
      oscillation and calcineurin activity.

PMID- 22615492
TI  - MicroRNA-206 regulates cell movements during zebrafish gastrulation by targeting
      prickle1a and regulating c-Jun N-terminal kinase 2 phosphorylation.
AB  - During vertebrate gastrulation, both concurrent inductive events and cell
      movements are required for axis formation. Convergence and extension (CE)
      movements contribute to narrowing and lengthening the forming embryonic axis.
      MicroRNAs (miRNAs) play a critical role in regulating fundamental cellular
      functions and developmental processes, but their functions in CE movements are
      not well known. Zebrafish mir206 is maternally expressed and present throughout
      blastulation and gastrulation periods. Either gain or loss of function of mir206
      leads to severe defects of convergent extension movements both cell autonomously
      and non-cell autonomously. Mosaic lineage tracing studies reveal that the
      formation of membrane protrusions and actin filaments is disturbed in mir206
      overexpressing embryos or mir206 morphants. Mechanistically, mir206 targets
      prickle1a (pk1a) mRNA and as a result regulates c-Jun N-terminal protein kinase 2
      (JNK2) phosphorylation. pk1a overexpression or knockdown can rescue convergent
      extension defects induced by mir206 overexpression or knockdown, respectively.
      Therefore, mir206 is an essential, novel regulator for normal convergent and
      extension movements by regulating mitogen-activated protein kinase (MAPK) JNK
      signaling.

PMID- 22615495
TI  - "This clinic is number one": a qualitative study of factors that contribute
      toward "successful" care at a South African Pediatric HIV/AIDS clinic.
AB  - HIV/AIDS has significantly affected health care practices. The need for high
      adherence and regular clinic visits places pressure on health care providers and
      patients. Poor quality of care has been described in many contexts, but some
      clinics have achieved excellent treatment results. Using a success case approach,
      this study aimed to understand factors which contribute to successful care at a
      South African pediatric HIV/AIDS clinic with documented high patient adherence
      and follow-up rates. Data included over 50 hours of ethnographic observations and
      interviews with a total of 35 clinic staff and caregivers. Thematic analysis
      highlighted strong congruence between caregiver and staff perceptions. Factors
      which seemed to contribute to successful care included organizational routines,
      staff-patient relationships, communication, teamwork, leadership, job commitment,
      caregivers' negative experiences at other clinics, and faith in the "life-saving"
      care at this clinic. Results suggest the need for all factors to be present in
      order to promote quality of care. Recommendations for other clinic settings are
      discussed.

PMID- 22615494
TI  - c-Src links a RANK/alphavbeta3 integrin complex to the osteoclast cytoskeleton.
AB  - RANK ligand (RANKL), by mechanisms unknown, directly activates osteoclasts to
      resorb bone. Because c-Src is key to organizing the cell's cytoskeleton, we asked
      if the tyrosine kinase also mediates RANKL-stimulated osteoclast activity. RANKL
      induces c-Src to associate with RANK(369-373) in an alphavbeta3-dependent manner.
      Furthermore, RANK(369-373) is the only one of six putative TRAF binding motifs
      sufficient to generate actin rings and activate the same cytoskeleton-organizing
      proteins as the integrin. While c-Src organizes the cell's cytoskeleton in
      response to the cytokine, it does not participate in RANKL-stimulated osteoclast
      formation. Attesting to their collaboration, alphavbeta3 and activated RANK
      coprecipitate, but only in the presence of c-Src. c-Src binds activated RANK via
      its Src homology 2 (SH2) domain and alphavbeta3 via its SH3 domain, suggesting
      the kinase links the two receptors. Supporting this hypothesis, deletion or
      inactivating point mutation of either the c-Src SH2 or SH3 domain obviates the
      RANK/alphavbeta3 association. Thus, activated RANK prompts two distinct signaling
      pathways; one promotes osteoclast formation, and the other, in collaboration with
      c-Src-mediated linkage to alphavbeta3, organizes the cell's cytoskeleton.

PMID- 22615496
TI  - The relationship of point-of-sale tobacco advertising and neighborhood
      characteristics to underage sales of tobacco.
AB  - Our objective was to determine how point-of-sale tobacco marketing may relate to
      sales to minors. The authors used data from a 2007 cross-sectional study of the
      retail tobacco marketing environments in the St. Paul, MN metropolitan area
      matched with a database of age-of-sale compliance checks (random, covert test
      purchases by a minor, coordinated by law enforcement) of tobacco retailers and
      U.S. Census data to test whether certain characteristics of advertising or
      neighborhoods were associated with compliance check failure. The authors found
      that tobacco stores were the most likely type of store to fail compliance checks
      (44% failure), supermarkets were least likely (3%). Aside from a marginally
      significant association with Hispanic population proportion, there was no other
      association between either store advertising characteristics or neighborhood
      demographics and stores' compliance check failure. Though our findings were null,
      the relationship between advertising and real youth sales may be more nuanced as
      compliance checks do not perfectly simulate the way youth attempt to purchase
      cigarettes.

PMID- 22615497
TI  - Judgment, resources, and complexity: a qualitative study of the experiences of
      systematic reviewers of health promotion.
AB  - Systematic reviews play an increasingly important role in decision making in
      health promotion and public health. However, little has been published on how
      systematic reviewers acquire necessary knowledge and skills, and on the
      challenges they face in producing reviews. Semistructured interviews were
      conducted with a purposive sample of 17 systematic reviewers of health promotion.
      They described practice, training, and mentoring as being key ways that they
      learned reviewing skills, often in combination. Practice-based learning was
      considered to be particularly beneficial. Training was generally easy to access,
      though questions were raised about the feasibility of training stakeholders such
      as health professionals to become reviewers. It was suggested that an
      understanding of research methods is beneficial for novice reviewers. While
      funding opportunities for doing reviews are available, long-term investment is
      needed to support an infrastructure for the production of high-quality systematic
      reviews of important health promotion priorities.

PMID- 22615499
TI  - Psychometric properties of the Listening Styles Profile (LSP-16): a replication
      study.
AB  - The Listening Style Profile (LSP-16) measures people's self-reported preferences
      for four listening styles that we habitually use when we listen. Research in this
      area is important for health care education since listening is a fundamental
      skill in all the health care professions. The aim of this study was to
      investigate the factor structure of the LSP-16's subscales when completed by a
      group of respondents from a large Australian university. Data from the LSP-16
      completed by 860 undergraduate health science students enrolled in eight
      different courses (response rate of 59%) were analyzed using maximum likelihood
      confirmatory factor analysis. The model fit indices of the maximum likelihood
      analysis demonstrate that the resultant models did not fit the data well. One
      item exhibited model misfit and reliability estimates and factor loadings were
      modest. The confirmatory factor analysis results did not support the overall
      latent factor structure of the LSP-16 as initially proposed by its authors.
      Further work is required to examine the underlying construct validity and other
      measurement properties of the LSP-16.

PMID- 22615498
TI  - What does it mean to "employ" the RE-AIM model?
AB  - Many grant proposals identify the use of a given evaluation model or framework
      but offer little about how such models are implemented. The authors discuss what
      it means to employ a specific model, RE-AIM, and key dimensions from this model
      for program planning, implementation, evaluation, and reporting. The authors
      report both conceptual and content specifications for the use of the RE-AIM model
      and a content review of 42 recent dissemination and implementation grant
      applications to National Institutes of Health  that proposed the use of this
      model. Outcomes include the extent to which proposals addressed the overall RE
      AIM model and specific items within the five dimensions in their methods or
      evaluation plans. The majority of grants used only some elements of the model
      (less than 10% contained thorough measures across all RE-AIM dimensions). Few met
      criteria for "fully developed use" of RE-AIM and the percentage of key issues
      addressed varied from, on average, 45% to 78% across the RE-AIM dimensions. The
      results and discussion of key criteria should help investigators in their use of
      RE-AIM and illuminate the broader issue of comprehensive use of evaluation
      models.

PMID- 22615500
TI  - Meta-analysis: an introduction using regression models.
AB  - Research synthesis of evaluation findings is a multistep process. An investigator
      identifies a research question, acquires the relevant literature, codes findings
      from that literature, and analyzes the coded data to estimate the average
      treatment effect and its distribution in a population of interest. The process of
      estimating the average treatment effect is meta-analysis. Meta-analysis is
      gaining popularity across the social sciences, but introductions and even
      advanced treatments of the subject are often formula-driven. Researchers, who
      apply formulas without understanding, risk both misapplication and
      misinterpretation. This article derives formulas used in meta-analysis using
      standard regression models so this article seeks to introduce readers with an
      understanding of regression analysis to meta-analysis, intending thereby to
      motivate and facilitate a deeper reading of the meta-analysis literature.

PMID- 22615501
TI  - The concept of stability of vitiligo: a reappraisal.
AB  - Stability is taken as the most important parameter before opting for any
      transplantation technique to treat vitiligo. But, simultaneous donor site
      repigmentation and depigmentation of grafts at the recipient site has been noted.
      Similarly donor site depigmentation with complete repigmentation of the recipient
      area with pigment growing out from each graft has been observed. Successful
      repigmentation after regrafting in previous punch failure cases has also been
      reported. Koebner's phenomenon from history (Kp-h) and test grafting were the
      only available indicators to assess stability. It is quite ironic to note that
      even after four decades of experience in vitiligo surgery, there seems to be
      little consensus among workers regarding the optimal required period of
      stability. Moreover, the exact concept of stability in vitiligo is itself still
      not transparent and defined beyond doubt Overdependence on KpH or TG may be
      sometimes misleading in vitiligo. These two reveal the apparent clinical
      stability only and that may not be the true reflection of stability status of the
      disease at the molecular level. Antimelanocyte cytotoxic reactivity was observed
      among CD8+ TCC isolated from perilesional biopsies of patients with vitiligo. An
      attempt should be made to clearly fathom and define stability, not merely only on
      clinical ground but along with electron microscopy and histoenzymological
      analysis of the perilesional and nonlesional skin of vitiligo patients. Probably
      some growth factors which are responsible for both mitogenic and melanogenic
      stimulation of melanocytes should also be taken into account. Some serological
      test(s) could guide us to measure these growth factors.

PMID- 22615503
TI  - Serum Lipid, Lipoprotein and Oxidatively Modified Low Density Lipoprotein Levels
      in Active or Inactive Patients with Behcet's Disease.
AB  - AIM: To determine serum lipid, lipoproteins and oxidized low density lipoprotein
      (oxLDL) levels in Behcet's disease (BD) and to evaluate the relationship of these
      parameters with the clinical activity of the disease. MATERIALS AND METHODS:
      Sixty-two patients (25 active, 37 inactive) and -26 healthy controls were
      included in the study. We measured serum oxLDL levels using the enzyme-linked
      immunosorbent assay method, and serum total cholesterol (TC), triglyceride (TG)
      and high density lipoprotein-cholesterol (HDL-C) levels by spectrophotometric
      method. RESULTS: Serum TG (108+/-70 mg/dL and 79+/-40 mg/dL, respectively;
      P<0.05), LDL-C (124+/-35 mg/dL and 108+/-26 mg/dL, respectively; P<0.05) and
      oxLDL (65+/-19 U/L and 53+/-10 U/L, respectively; P<0.01) levels were
      significantly higher in patients than in controls, but HDL-C levels were
      significantly lower in patients than in controls (39+/-11 mg/dL and 50+/-13
      mg/dL, respectively; P<0.05). The levels of oxLDL in patients were found to
      correlate with those of TC and LDL-C. Neither the lipid parameters nor the oxLDL
      levels in the patients with active disease (n=25) were different than those in
      the patients who were in inactive stage (n=37). Serum levels of oxLDL in the
      patients with active and inactive disease were significantly higher than those in
      controls (66+/-19 U/L, 65+/-19 U/L, and 53+/-10 U/L, respectively; P<0.05).
      CONCLUSIONS: We conclude that the increase of TG, LDL-C and oxLDL levels and the
      decrease of HDL-levels may indicate that there is a tendency to atherothrombotic
      process in patients with BD. Inflammation and immunologic reactions in BD may be
      caused by a response to elevated oxLDL. TG, LDL-C and oxLDL are not useful
      markers for the severity of the disease activity.

PMID- 22615502
TI  - The role of cytokines in the pathomechanism of cutaneous disorders.
AB  - Cytokines are produced transiently by cutaneous cells in response to immune
      stimuli. They are non-immunoglobulin proteins and glycoproteins. Cytokines, which
      are signaling molecules, act by sending downstream signals to various cells
      through a number of signal transduction pathways and by binding to cytokine
      receptors on the surface of cells. Cytokines regulate immunity and inflammation
      and thus play an important role in the pathogenesis of various cutaneous
      disorders.

PMID- 22615504
TI  - Skin tags and acanthosis nigricans in patients with hepatitis C infection in
      relation to insulin resistance and insulin like growth factor-1 levels.
AB  - BACKGROUND: Skin tags (ST) are papillomas commonly found in the neck, axillae of
      middle-aged and elderly people AIM: Insulin and insulin-like growth factor (IGF
      1) levels are affected by hepatitis C virus (HCV) infection and both of them may
      be implicated in the etiopathogenesis of ST and acanthosis nigricans (AN) through
      their proliferative and differentiating properties. So, the aim of this work was
      to evaluate the impact of HCV infection on ST and AN through the estimation of
      insulin resistance and IGF-1. MATERIALS AND METHODS: PARTICIPANTS WERE ARRANGED
      INTO FOUR GROUPS: (ST +ve / HCV +ve) 23 subjects, (ST+ / HCV -ve) 19 subjects,
      (HCV -ve / ST-ve) 20 subjects and (ST-ve /HCV +ve) 22 subjects. Age, ST size,
      color, number, AN, fasting glucose, fasting insulin, insulin resistance, IGF-1,
      HCV-antibodies (Ab) were recorded. RESULTS: The mean number of ST in Group 1 was
      half the number of ST in Group 2 (11.0+/-9.3 / 22.3+/-14.0) (P=0.005). The
      difference in insulin resistance between the same groups was non-significant
      (13.1+/-10.6 / 9.0+/-5.5) (P=0.441) while the difference in IGF-1 was
      statistically significant (218.6+/-46.2 /285.4+/-32.8) (P=0.002). The
      multivariate logistic regression for the variables revealed that insulin
      resistance is the only factor affecting the occurrence of ST (OR=1.096, P=0.023).
      Multivariate regression analysis for the variables showed that HCV was borderline
      but not a significant factor affecting the number of ST (Beta=-0.409, P=0.053).
      The number of patients with AN was doubled in Group 2 in comparison to Group 1
      but this was non significant 3(13%) / 6(32%) (P=0.2800). CONCLUSION: HCV is
      associated with a significant decrease in the ST number and in the serum level of
      IGF-1 together with an obvious decrease in the occurrence of AN. Our results may
      point to the entrant effect of insulin resistance and IGF-1 in ST and AN
      development. The current study suggests the evaluation of IGF-1-lowering agents
      in the control of ST and AN especially in the females with polycystic ovary and
      in the prevention of the recurrence of ST after surgical removal.

PMID- 22615505
TI  - Prevalence of oral, skin, and oral and skin lesions of lichen planus in patients
      visiting a dental school in southern India.
AB  - BACKGROUND: Lichen planus (LP) is a mucocutaneous disease that is relatively
      common among adult population. LP can present as skin and oral lesions. This
      study highlights the prevalence of oral, skin, and oral and skin lesions of LP.
      AIMS: The aim of this study was to evaluate the prevalence of oral, skin, and
      oral and skin lesions of LP from a population of patients attending the
      Department of Oral Medicine and Radiodiagnosis, Pushpagiri College of Dental
      Sciences, Tiruvalla, Kerala, India. MATERIALS AND METHODS: A cross-sectional
      study was designed to evaluate the prevalence of oral, skin, and oral and skin
      lesions of LP. This is a ongoing prospective study with results of 2 years being
      reported. LP was diagnosed on the basis of clinical presentation and
      histopathological analysis of mucosal and skin biopsy done for all patients
      suspected of having LP. Statistical analysis was carried out using SPSS
      (Statistical package for social sciences) software version 14. To test the
      statistical significance, chi-square test was used. RESULTS: Out of 18,306
      patients screened, 8,040 were males and 10,266 females. LP was seen in 118 cases
      (0.64%). Increased prevalence of LP was observed in middle age adults (40-60
      years age group) with lowest age of 12 years and highest age of 65 years. No
      statistically significant differences were observed between the genders in skin
      LP group (P=0.12) and in oral and skin LP groups (P=0.06); however, a strong
      female predilection was seen in oral LP group (P=0.000036). The prevalence of
      cutaneous LP in oral LP patients was 0.06%. CONCLUSION: This study showed an
      increased prevalence of oral LP than skin LP, and oral and skin LP with a female
      predominance.

PMID- 22615506
TI  - The impact of chronic urticaria on the quality of life in Indian patients.
AB  - BACKGROUND: Besides the relief of symptoms, the main purpose of any treatment
      must be to ensure a better quality of life (QOL). Mere recording of symptoms
      reveals their severity and frequency, but gives scant information on its effect
      on QOL. AIM: The study was designed to assess QOL in Indian patients with chronic
      urticaia (CU). SUBJECTS AND METHODS: We used the validated CU-QOL by Bairadani et
      al., consisting of five domains and each domain consisting of several items. Each
      item was scored from 1 to 5 (score 5 = most affected, score 1 = not affected).
      CRITERIA FOR INCLUSION: Patients having symptoms of rash and pruritis on most of
      the days for at least 6 weeks were enrolled. CRITERIA FOR EXCLUSION: If the
      individuals had CU secondary to any other disease, they were excluded. RESULTS:
      We enrolled 48 patients. The means of the domains, the items, and the frequency
      of occurrence of an item were tabulated. The highest mean scores were in the
      domains of symptoms, followed by sleep disturbances, life activities, looks, and
      limits. The highest mean scores for the items were for pruritis and wheals
      followed by sleep disturbances, mood changes, nervousness, embarrassment,
      fatigue, loss of concentration, reduced work, and social relationships. We also
      observed a significant relationship among individual items. It is possible that
      they may have an additive effect. CONCLUSIONS: Even though CU significantly
      affected many items, patients were rarely aware of them. There was a significant
      inter-item correlation, suggesting that items might be aggravating each other. It
      is important to address the issues regarding QOL along with symptoms for better
      management of CU.

PMID- 22615507
TI  - A retrospective analysis of histopathology of 64 cases of lepra reactions.
AB  - BACKGROUND: Lepra reactions are not always diagnosable under the microscope. We
      analyzed skin histopathology in 64 cases of lepra reaction. AIM: To make detailed
      observations on histopathologic features of type 1 and type 2 lepra reaction
      (erythema nodosum leprosum, ENL). MATERIALS AND METHODS: In this retrospective
      study, we included 64 patients diagnosed during a 3-year period as lepra reaction
      based on clinico-pathological co-relation. RESULTS: Out of the 64 patients, 22
      were of type 1 reaction and 42 of ENL. The most consistent finding in type 1
      reaction was papillary dermal edema (86%) followed by pyknosis of lymphocytes
      (77%) and intercellular edema within granuloma (73%). Surprisingly,
      folliculotropism of lymphocytes was seen in 55% and subcutaneous infiltration in
      36%. In ENL, the most common finding was presence of neutrophils within the
      granuloma (100%), followed by leukocytoclasia (81%), papillary dermal edema
      (81%), and neutrophilic panniculitis (69%). Fibrin in the vessel wall or/and
      granulomas was noted in only 38% while fibrin thrombi in the vessel walls were
      seen in only 12% of cases. CONCLUSION: Infiltration of macrophage granulomas by
      neutrophils is a reliable sign of ENL. Classical signs of vasculitis are not
      always present in ENL. Folliculotropism and lymphocytic panniculitis were
      frequent in type 1 reactions while neutrophilic panniculitis was common with ENL.

PMID- 22615508
TI  - Comparison of intralesional two percent zinc sulfate and glucantime injection in
      treatment of acute cutaneous leishmaniasis.
AB  - INTRODUCTION: Cutaneous leishmaniasis is an endemic disease in developing
      countries caused by different species of leishmania parasite, and if left
      untreated, it will result in a deformed scar after a relatively long period.
      Although various systemic and topical treatments have been proposed for
      leishmaniasis, pentavalent Antimony compounds remain the first-line treatment for
      it. Considering the cases with treatment failure, potential side effects and
      reluctance of patients to receive the drug, there are continuing efforts to find
      better treatment alternatives. AIM: Comparison of the effect of intralesional 2%
      zinc sulfate injection with Glucantime in treatment of acute cutaneous
      leishmaniasis. MATERIALS AND METHODS: In this clinical trial, 45 patients with
      clinical diagnosis of cutaneous leishmaniasis and positive direct smear for
      leishman body were treated by intralesional injection of either 2% zinc sulfate
      or Glucantime. After simple randomization, in one group the patients were treated
      with 2 bouts of intralesional 2% zinc sulfate with a 2-week interval, and in the
      other group they were treated with 6 weekly bouts of intralesional Glucantime.
      The patients were monitored in two week intervals for 8 weeks. Healing of the
      lesions was evaluated clinically and by direct smear, and the data were analyzed
      using SPSS (11.5) software, t-Student, Mann-Whitney and Analysis of covariance
      (ANCOVA) statistical tests. FINDINGS: In the end of study, 34 patients completed
      the study, 10 of whom received intralesional Glucantime and 24 of whom received
      intralesional 2% zinc sulfate. The healing rate after 8 weeks was 80% in the
      group receiving intralesional Glucantime and 33.3% in the one receiving 2% zinc
      sulfate (P=0.009). CONCLUSION: Based on the results of this study, intralesional
      injection of 2% zinc sulfate was less effective in treatment of cutaneous
      leishmaniasis than intralesional Glucantime.

PMID- 22615509
TI  - Treatment of cutaneous lesion of 20 years' duration caused by leishmanization.
AB  - The inoculation of live Leishmania (L.) major to produce a single lesion is
      called leishmanization (LZ). LZ lesion upon cure prevents further natural
      infection which might be multiple lesions on unwanted sites such as face.
      Cutaneous leishmaniasis (CL) usually leads to a self healing lesion; though
      rarely the lesion persists and becomes refractory to all types of remedies. Here,
      we present a 41-year-old patient with a 20-year history of cutaneous lesion
      caused by leishmanization. The causative agent is identified as L. major. The
      patient did not respond to treatment with meglumine antimoniate, 20 mg/kg/day
      Sb(+5) for three weeks and allopurinol 10 mg/kg for four weeks. After two months,
      the same treatment was repeated. In addition, a topical liposomal preparation
      containing 10% paromomycin sulfate was administered twice a day for four weeks.
      The lesion showed marked improvement during the treatment and was eventually
      completely healed.

PMID- 22615510
TI  - Variable response to propranolol therapy for infantile hemangiomas.
AB  - Since propranolol was accidentally discovered to induce involution of
      hemangiomas, it is being used by many clinicians with a favourable response. We
      present our experience with use of propranolol and report three infants with
      hemangiomas who were treated with propranolol. First infant had a marked
      involution of the lesion; second infant had a appreciable response while the
      third infant had a initial minimal response with progressive increase in size of
      the lesion.

PMID- 22615511
TI  - Comparison of Red and Infrared Low-level Laser Therapy in the Treatment of Acne
      Vulgaris.
AB  - BACKGROUND/PURPOSE: Acne vulgaris is a very prevalent skin disorder and remains a
      main problem in practice. Recently, phototherapy with various light spectrums for
      acne has been used. There are some evidences that low-level laser therapy (LLLT)
      has beneficial effect in the treatment of acne lesions. In this study, two
      different wavelengths of LLLT (630 and 890 nm) were evaluated in treatment of
      acne vulgaris. MATERIALS AND METHODS: This study was a single-blind randomized
      clinical trial. Patients with mild to moderate acne vulgaris and age above 18
      years and included were treated with red LLLT (630 nm) and infrared LLLT (890 nm)
      on the right and left sides of the face respectively, twice in a week for 12
      sessions, and clinically assessed at baseline and weeks 2, 4, 6, and 8. RESULTS:
      Twenty-eight patients were participated in this study. Ten weeks after treatment
      acne lesion were significantly decreased in the side treated by 630 nm LLLT
      (27.7+/-12.7 to 6.3+/-1.9) (P<0.001), but this decrease was not significant in
      the site treated by 890 nm LLLT (26.9+/-12.4 to 22.2+/-8.5) (P>0.05). CONCLUSION:
      Red wavelength is safe and effective to be used to treat acne vulgaris by LLLT
      compared to infrared wavelength.

PMID- 22615512
TI  - Laptop induced erythema ab igne.
AB  - Erythema ab igne is a reticular, pigmented dermatosis caused by prolonged and
      repeated exposure to infrared radiation that is insufficient to produce a burn.
      The use of laptop computers has increased manifold in the recent past. Prolonged
      contact of the laptop with the skin can lead to the development of erythema ab
      igne. We present a case of erythema ab igne secondary to laptop use in an Indian
      student.

PMID- 22615513
TI  - Blastomycosis presenting as solitary nodule: a rare presentation.
AB  - Blastomycosis is a chronic granulomatous and suppurative mycosis, caused by
      Blastomyces dermatitidis, which in the great majority of cases presents as a
      primary pulmonary disease. Primary cutaneous blastomycosis is very rare. We
      present a 57-year-old female patient with a solitary, slowly progressive nodule
      over upper lip of 21/2 months duration. Initially, differential diagnosis of
      cutaneous leishmaniasis, pyoderma and deep mycoses were entertained. Slit smear
      preparation was suspicious of deep mycotic infection which was subsequently
      confirmed by biopsy and culture.

PMID- 22615514
TI  - Necrodestructive herpes zoster.
AB  - Herpes Zoster (HZ) is a self-limiting viral infection of skin and mucosa caused
      by Varicella zoster virus. Cutaneous lesions of HZ usually heal without any
      scarring and hyper/hypopigmentation. Though, post-inflammatory depigmentation and
      deep scarring can occur in immunocompromised or HIV positive individuals. The
      present report is of a elderly immunocompetent female who had HZ involving the
      ophthalmic division (including nasociliary branch) of trigeminal nerve. The
      lesions over nose caused mutilating scarring resulting in complete obstruction of
      the right anterior nare.

PMID- 22615515
TI  - Unilateral nevoid telangiectasia: a rare disease?
AB  - Unilateral nevoid telangiectasia is a rare congenital or acquired disorder. The
      majority of the authors propose that it is probably related to elevated estrogen
      receptors, although other authors advocate different theories. We report the
      occurrence of lesions clinically compatible with this diagnosis in a child and
      two adults. Only one of the patients had a background of estrogen elevation. The
      other two patients were healthy. We stress the occurrence of this disease in a
      rare idiopathic form and point out to the relative elevated incidence of it,
      because the patients discussed in this article were observed for a short period
      of time.

PMID- 22615516
TI  - Solitary cylindroma with malignant transformation.
AB  - A 59-year-old woman presented with a history of rapidly progressive recurrent
      tumor of 6.5 cm diameter of the scalp. Histopathological examination revealed a
      case of malignant cylindroma. There has been no recurrence or metastases and the
      patient is disease free at the end of 15 months postoperatively. Malignant
      transformation occurs less often in solitary form of cylindroma, but once
      transformed, tumors behave aggressively with extensive local infiltrative growth
      or metastases. The case is reported to document a rare case of malignant
      cylindroma arising in a patient with solitary cylindroma on the parieto-temporal
      region.

PMID- 22615517
TI  - Recurrent facial urticaria following herpes simplex labialis.
AB  - We describe recurrent acute right-sided facial urticaria associated with herpes
      labialis infection in a middle-aged female patient. Antiviral medications and
      antihistamines not only successfully cleared the herpes infection and urticaria
      but also prevented further recurrences.

PMID- 22615518
TI  - Postpartum pemphigoid gestationis.
AB  - Pemphigoid gestationis (PG) or herpes gestationis is a rare autoimmune
      subepidermal blistering disorder associated with pregnancy. The condition
      typically develops during the second or third trimester of pregnancy, but has
      been rarely reported in the first trimester and postpartum period. Here, we
      report a case of PG that presented for the first time in the postpartum period,
      associated with a low birth weight baby.

PMID- 22615519
TI  - Secondary lymphangioma of vulva: a report of two cases.
AB  - Secondary lymphangiomas or acquired lymphangiomas of vulva represent dilatation
      of upper dermal lymphatics following damage to previously normal deep lymphatics.
      They have been reported to occur following various infections, surgeries and
      radiotherapy which can cause damage to deep lymphatics.Treatment options in the
      management of secondary lymphangiomas include surgical resection, carbon dioxide
      laser vaporisation, sclerosing agents etc. We report two cases of secondary
      lymphangioma of vulva that followed radiotherapy for carcinoma of cervix. Both
      the patients were treated successfully by surgery.

PMID- 22615520
TI  - Limits of fine-needle aspiration cytology in diagnosing pilomatrixoma: a series
      of 25 cases with clinico-pathologic correlations.
AB  - BACKGROUND: Pilomatrixoma (PMX) is a benign, quite uncommon, skin neoplasm, which
      is frequently misdiagnosed by clinicians. AIM: We have analyzed 25 PMX to
      determine the agreement between clinical diagnosis, preoperative FNA
      characteristics, and corresponding histopathological specimens; moreover,
      reliable cytologic criteria for PMX and the differential diagnosis to avoid
      cytological pitfalls have been emphasized. MATERIALS AND METHODS: By fine-needle
      aspiration (FNA) cytology a series of consecutive cases of PMX collected during
      last 5 years were studied. Smears were stained by Papanicolau and May-Grunwald
      Giemsa. RESULTS: Patients affected by PMX were 11 males, 14 females (ratio
      1:1.27); the mean age was 32.72 years with age range 3-78 years, being 72%
      (18/25) of patients 40 years or less. PMX was mainly distributed in the head-neck
      region (52%), scalp (16%), upper/lower arms (28%), and chest (4%). The observed
      diagnostic cytological features were represented by clusters of basaloid
      epithelial cells, shadow or ghost cells, inflammatory background, calcification,
      and giant cells. Unfortunately, not all these morphological aspects were always
      disclosed in smears, thus making the cytological preoperative diagnosis
      questionable and problematic. CONCLUSIONS: The experience of a well-trained
      cytopathologist should distinguish the relevant FNA features in terms of smear
      background, architecture, and cell morphology. The most dangerous mistake in FNA
      diagnosis of PMX regards a diagnosis of primary malignant or metastatic cutaneous
      lesions.

PMID- 22615521
TI  - Reed's Syndrome.

PMID- 22615522
TI  - T-cell prolymphocytic leukemia with cutaneous involvement as the presenting
      feature.

PMID- 22615523
TI  - Disseminated discoid lupus erythematosus leading to squamous cell carcinoma.

PMID- 22615524
TI  - IFAP Syndrome with Rickets and Normal Vitamin D Status.

PMID- 22615525
TI  - Keratotic papule with a collarette of skin.

PMID- 22615527
TI  - Effects of tiotropium on sympathetic activation during exercise in stable chronic
      obstructive pulmonary disease patients.
AB  - BACKGROUND: Tiotropium partially relieves exertional dyspnea and reduces the risk
      of congestive heart failure in chronic obstructive pulmonary disease (COPD)
      patients. However, its effect on the sympathetic activation response to exercise
      is unknown. AIMS: This study aimed to determine whether tiotropium use results in
      a sustained reduction in sympathetic activation during exercise. METHODS: We
      conducted a 12-week, open-label (treatments: tiotropium 18 MUg or oxitropium 0.2
      mg * 3 mg), crossover study in 17 COPD patients. Treatment order was randomized
      across subjects. The subjects underwent a pulmonary function test and two modes
      of cardiopulmonary exercise (constant work rate and incremental exercise) testing
      using a cycle ergometer, with measurement of arterial catecholamines after each
      treatment period. RESULTS: Forced expiratory volume in 1 second and forced vital
      capacity were significantly larger in the tiotropium treatment group. In constant
      exercise testing, exercise endurance time was longer, with improvement in dyspnea
      during exercise and reduction in dynamic hyperinflation in the tiotropium
      treatment group. Similarly, in incremental exercise testing, exercise time,
      carbon dioxide production, and minute ventilation at peak exercise were
      significantly higher in the tiotropium treatment group. Plasma norepinephrine
      concentrations and dyspnea intensity were also lower during submaximal isotime
      exercise and throughout the incremental workload exercise in the tiotropium
      treatment group. CONCLUSION: Tiotropium suppressed the increase of sympathetic
      activation during exercise at the end of the 6-week treatment, as compared with
      the effect of oxipropium. This effect might be attributed to improvement in lung
      function and exercise capacity and reduction in exertional dyspnea, which were
      associated with decreases in respiratory frequency and heart rate and reduced
      progression of arterial acidosis.

PMID- 22615528
TI  - Correlation of health-related quality of life with other disease severity indices
      in Indian chronic obstructive pulmonary disease patients.
AB  - BACKGROUND: Improvement in quality of life (QOL) has become a focus for the
      management of incurable chronic diseases, including chronic obstructive pulmonary
      disease (COPD). This study investigates factors influencing the QOL of patients
      with COPD in India. METHODS: Seventy-three consecutive COPD patients visiting an
      outpatient pulmonary clinic underwent health-related QOL (HRQOL) assessment using
      the World Health Organization's QOL abbreviated questionnaire and St George's
      Respiratory Questionnaire (SGRQ). Symptom severity and grade of dyspnea were
      estimated by the Chronic Lung Disease Severity Index (CLD) and Medical Research
      Council assessments, and patient demographic data were collected. Spirometry and
      6-minute walk tests were performed to assess lung function and functional status.
      RESULTS: Patients with COPD showed significantly reduced HRQOL when measured by
      the World Health Organization's QOL abbreviated questionnaire and the SGRQ. CLD
      estimate for severity of lung disease (P < 0.001), Medical Research Council
      assessment for dyspnea (P < 0.01), and duration of illness (P < 0.05) showed
      close correlation with HRQOL. Worsening forced expiratory volume in 1 second and
      6-minute walk test results closely correlated with poorer HRQOL (P < 0.01). No
      association between QOL and age, quantum of smoking, education, comorbid
      illnesses, or occupational exposure was found. CONCLUSION: This study showed that
      Indian patients with COPD had reduced HRQOL. Longer disease duration, patient
      perception of disease severity, and worsening dyspnea impacted negatively on
      HRQOL.

PMID- 22615529
TI  - The preparation and characterization of gold-conjugated polyphenol nanoparticles
      as a novel delivery system.
AB  - Nanogold particles are commonly used in nanomedicine. We generated physical
      nanogold (pNG) conjugated with different ratios of epigallocatechin-3-gallate
      (EGCG) and evaluated its physicochemical properties, antioxidant activity, and
      cytotoxicity in vitro as well as anticancer activity in vivo. Results showed that
      the EGCG-pNG conjugates were successfully prepared at ratios between 23:1 and
      23:5, with the percentage of EGCG content increasing with the EGCG:pNG ratio from
      23:1 (2.0% +/- 0.02%) to 23:5 (28% +/- 0.3%). EGCG-pNG particles at ratios of
      23:1 and 23:5 demonstrated significantly decreased size from 500 to 20 nm and
      decreasing zeta potentials of 21 mV to -22 mV, respectively. At a ratio of
      23:2.5, the EGCG-pNG particles (27% EGCG, 50 nm in size, zeta potential of -8 mV)
      showed longer EGCG activity half-life (110 days vs 5 hours), controlled release
      (2 hours vs 30 minutes), and higher antioxidant activity (four times), as well as
      inhibition of tumor cell growth, than controls. The present study indicated that
      EGCG-pNG possesses promising therapeutic potential, based on its strong free
      radical scavenging and anticancer activities.

PMID- 22615530
TI  - Preparation, characterization, and cytotoxicity of CPT/Fe2O3-embedded PLGA
      ultrafine composite fibers: a synergistic approach to develop promising
      anticancer material.
AB  - The aim of this study was to fabricate camptothecin/iron(III) oxide (CPT/Fe2O3)
      loaded poly(D,L-lactide-co-glycolide) (PLGA) composite mats to modulate the CPT
      release and to improve the structural integrity and antitumor activity of the
      released drug. The CPT/Fe2O3-loaded PLGA ultrafine fibers were prepared for the
      first time by electrospinning a composite solution of CPT/Fe2O3 and neat PLGA (4
      weight percent). The physicochemical characterization of the electrospun
      composite mat was carried out by scanning electron microscopy, energy dispersive
      X-ray spectroscopy, electron probe microanalysis, thermogravimetry, transmission
      electron microscopy, ultraviolet-visible spectroscopy, and X-ray diffraction
      pattern. The medicated composite fibers were evaluated for their cytotoxicity on
      C2C12 cells using Cell Counting Kit-8 assay (Sigma-Aldrich Corporation, St Louis,
      MO). The in vitro studies indicated a slow and prolonged release over a period of
      96 hours with mild initial burst. Scanning electron microscopy, thermogravimetry,
      and X-ray diffraction studies confirmed the interaction of CPT/Fe2O3 with the
      PLGA matrix and showed that the crystallinity of CPT decreased after loading.
      Incorporation of CPT in the polymer media affected both the morphology and the
      size of the CPT/Fe2O3-loaded PLGA composite fibers. Electron probe microanalysis
      and energy dispersive X-ray spectroscopy results confirmed well-oriented
      composite ultrafine fibers with good incorporation of CPT/Fe2O3. The cytotoxicity
      results illustrate that the pristine PLGA did not exhibit noteworthy
      cytotoxicity; conversely, the CPT/Fe2O3 composite fibers inhibited C2C12 cells
      significantly. Thus, the current work demonstrates that the CPT/Fe2O3-loaded PLGA
      composite fibers represent a promising chemotherapeutic system for enhancing
      anticancer drug efficacy and selectively targeting cancer cells in order to treat
      diverse cancers.

PMID- 22615531
TI  - Association between calcifying nanoparticles and placental calcification.
AB  - BACKGROUND: The purpose of this study was to examine the possible contribution of
      calcifying nanoparticles to the pathogenesis of placental calcification. METHODS:
      Calcified placental tissues and distal tissue samples were collected from 36
      confirmed placental calcification cases. In addition, 20 normal placental tissue
      samples were obtained as a control group. All the tissue samples were cultured
      using special nanobacterial culture methods. The cultured calcifying
      nanoparticles were examined by transmission electron microscopy (TEM), and their
      growth was monitored by optical density (OD) at a wavelength of 650 nm. 16S rRNA
      gene expression of the cultured calcifying nanoparticles was also isolated and
      sequenced. RESULTS: Novel calcifying nanoparticles wrapped with electron-dense
      shells between 50 nm to 500 nm in diameter were observed in the extracellular
      matrix of calcified placental tissues. They were detected in placental villi and
      hydroxyapatite crystals, and contained "nucleic acid-like materials". After
      isolation and four weeks of culture, 28 of 36 calcified placental tissue samples
      showed white granular precipitates attached to the bottom of the culture tubes.
      OD(650) measurements indicated that the precipitates from the calcified placental
      tissues were able to grow in culture, whereas no such precipitates from the
      control tissues were observed. The 16S rRNA genes were isolated from the cultured
      calcifying nanoparticles and calcified placental tissues, and their gene
      sequencing results implied that calcifying nanoparticles were novel nanobacteria
      (GenBank JF823648). CONCLUSION: Our results suggest that these novel calcifying
      nanoparticles may play a role in placental calcification.

PMID- 22615532
TI  - The effects of magnetite (Fe3O4) nanoparticles on electroporation-induced inward
      currents in pituitary tumor (GH3) cells and in RAW 264.7 macrophages.
AB  - AIMS: Fe3O4 nanoparticles (NPs) have been known to provide a distinct image
      contrast effect for magnetic resonance imaging owing to their super paramagnetic
      properties on local magnetic fields. However, the possible effects of these NPs
      on membrane ion currents that concurrently induce local magnetic field
      perturbation remain unclear. METHODS: We evaluated whether amine surface-modified
      Fe3O4 NPs have any effect on ion currents in pituitary tumor (GH3) cells via
      voltage clamp methods. RESULTS: The addition of Fe3O4 NPs decreases the amplitude
      of membrane electroporation-induced currents (I(MEP)) with a half-maximal
      inhibitory concentration at 45 MUg/mL. Fe3O4 NPs at a concentration of 3 mg/mL
      produced a biphasic response in the amplitude of I(MEP), ie, an initial decrease
      followed by a sustained increase. A similar effect was also noted in RAW 264.7
      macrophages. CONCLUSION: The modulation of magnetic electroporation-induced
      currents by Fe3O4 NPs constitutes an important approach for cell tracking under
      various imaging modalities or facilitated drug delivery.

PMID- 22615533
TI  - Evolving forecasting classifications and applications in health forecasting.
AB  - Health forecasting forewarns the health community about future health situations
      and disease episodes so that health systems can better allocate resources and
      manage demand. The tools used for developing and measuring the accuracy and
      validity of health forecasts commonly are not defined although they are usually
      adapted forms of statistical procedures. This review identifies previous
      typologies used in classifying the forecasting methods commonly used in
      forecasting health conditions or situations. It then discusses the strengths and
      weaknesses of these methods and presents the choices available for measuring the
      accuracy of health-forecasting models, including a note on the discrepancies in
      the modes of validation.

PMID- 22615534
TI  - Treatment-completion rates with olanzapine long-acting injection versus
      risperidone long-acting injection in a 12-month, open-label treatment of
      schizophrenia: indirect, exploratory comparisons.
AB  - BACKGROUND: Little is known about the comparative effectiveness of atypical
      antipsychotics in long-acting injection formulation. Due to the absence of head
      to-head studies comparing olanzapine long-acting injection and risperidone long
      acting injection, this study was intended to make exploratory, indirect, cross
      study comparisons between the long-acting formulations of these two atypical
      antipsychotics in their effectiveness in treating patients with schizophrenia.
      METHODS: Indirect, cross-study comparisons between olanzapine long-acting
      injection and risperidone long-acting injection used 12-month treatment
      completion rates, because discontinuation of an antipsychotic for any cause is a
      recognized proxy measure of the medication's effectiveness in treating
      schizophrenia. Following a systematic review of the literature, two indirect
      comparisons were conducted using open-label, single-cohort studies in which
      subjects were stabilized on an antipsychotic medication before depot initiation.
      The first analysis compared olanzapine long-acting injection (one study) with
      pooled data from nine identified risperidone long-acting injection studies. The
      second analysis was a "sensitivity analysis," using only the most similar
      studies, one for olanzapine long-acting injection and one for risperidone long
      acting injection, which shared near-identical study designs and involved study
      cohorts with near-identical patient characteristics. Pearson Chi-square tests
      assessed group differences on treatment-completion rates. RESULTS: Comparison of
      olanzapine long-acting injection data (931 patients) with the pooled data from
      the nine risperidone long-acting injection studies (3950 patients) provided
      almost identical 12-month treatment-completion rates (72.7% versus 72.4%; P =
      0.87). When the two most similar studies were compared, the 12-month completion
      rate for olanzapine long-acting injection was significantly higher than for
      risperidone long-acting injection (81.3% versus 47.0%; P < 0.001). However, any
      conclusions drawn from this comparison may be limited by differences in the
      studies' geographic catchment areas. CONCLUSION: Using treatment-completion rates
      as a proxy measure of medication effectiveness, olanzapine long-acting injection
      did not differ significantly from risperidone long-acting injection when
      including all eligible studies. However, the findings of this exploratory
      analysis should be interpreted with caution, considering the methodological
      limitations of these indirect, cross-study comparisons.

PMID- 22615535
TI  - Simultaneous bilateral posterior fracture dislocation of the shoulders in a young
      man with unexpected severe vitamin D deficiency.
AB  - Simultaneous bilateral posterior fracture dislocation of the shoulders is a rare
      clinical presentation. There are three main etiologies described in the
      literature. Given that it presents with relatively uncharacteristic symptoms, in
      many cases it is diagnosed late. We present the case of a man who was admitted
      with bilateral posterior fracture dislocation of the shoulders following a
      seizure. Investigations revealed severe vitamin D deficiency as the principal
      contributory factor to his injury. This is an important association because
      failure to recognize and treat this can result in significant morbidity in
      susceptible groups.

PMID- 22615536
TI  - Serum levels of RBP4 and adipose tissue levels of PTP1B are increased in obese
      men resident in northeast Scotland without associated changes in ER stress
      response genes.
AB  - BACKGROUND: Retinol-binding protein 4 (RBP4) is an adipokine identified as a
      marker of insulin resistance in mice and humans. Protein tyrosine phosphatase 1B
      (PTP1B) expression levels as well as other genes involved in the endoplasmic
      reticulum (ER) stress response are increased in adipose tissue of obese, high-fat
      diet-fed mice. In this study we investigated if serum and/or adipose tissue RBP4
      protein levels and expression levels of PTP1B and other ER stress-response genes
      are altered in obese and obese/diabetic men resident in northeast Scotland.
      METHODS: WE STUDIED THREE GROUPS OF MALE VOLUNTEERS: (1) normal/overweight (body
      mass index [BMI] < 30), (2) obese (BMI > 30), and (3) obese/diabetic (BMI > 30)
      controlling their diabetes either by diet or the antidiabetic drug metformin. We
      analyzed their serum and adipose tissue RBP4 protein levels as well as adipose
      tissue mRNA expression of PTP1B, binding immunoglobulin protein (BIP), activated
      transcription factor 4 (ATF4), and glucose-regulated protein 94 (GRP94) alongside
      other markers of adiposity (percentage body fat, leptin, cholesterol,
      triglycerides) and insulin resistance (oral glucose tolerance tests, insulin,
      homeostatic model assessment-insulin resistance, C-reactive protein, and
      adiponectin). RESULTS: We found that obese Scottish subjects had significantly
      higher serum RBP4 protein levels in comparison to the normal/overweight subjects
      (P < 0.01). Serum RBP4 levels were normalized in obese/diabetic subjects treated
      with diet or metformin (P < 0.05). Adipose tissue RBP4 protein levels were
      comparable between all three groups of subjects as were serum and adipose
      transthyretin levels. Adipose tissue PTP1B mRNA levels were increased in obese
      subjects in comparison to normal/overweight subjects (P < 0.05); however diet
      and/or metformin treatment did not reverse this effect. Adipose tissue BIP, ATF4,
      and GRP94 expression levels were unchanged in obese and obese/diabetic subjects.
      CONCLUSIONS: Human obesity results in an increase in serum but not adipose tissue
      RBP4 protein levels, and these are normalized in obese/diabetic subjects, which
      exhibit improvements in insulin sensitivity through diet or metformin treatment.
      However, while adipose tissue PTP1B mRNA levels increase in obese Scottish
      subjects, these remain high in obese/diabetics on diet or metformin treatment.

PMID- 22615537
TI  - Relative nutritional deficiencies associated with centrally acting monoamines.
AB  - BACKGROUND: Two primary categories of nutritional deficiency exist. An absolute
      nutritional deficiency occurs when nutrient intake is not sufficient to meet the
      normal needs of the system, and a relative nutritional deficiency exists when
      nutrient intake and systemic levels of nutrients are normal, while a change
      occurs in the system that induces a nutrient intake requirement that cannot be
      supplied from diet alone. The purpose of this paper is to demonstrate that the
      primary component of chronic centrally acting monoamine (serotonin, dopamine,
      norepinephrine, and epinephrine) disease is a relative nutritional deficiency
      induced by postsynaptic neuron damage. MATERIALS AND METHODS: Monoamine
      transporter optimization results were investigated, reevaluated, and correlated
      with previous publications by the authors under the relative nutritional
      deficiency hypothesis. Most of those previous publications did not discuss the
      concept of a relative nutritional deficiency. It is the purpose of this paper to
      redefine the etiology expressed in these previous writings into the realm of
      relative nutritional deficiency, as demonstrated by monoamine transporter
      optimization. The novel and broad range of amino acid precursor dosing values
      required to address centrally acting monoamine relative nutritional deficiency
      properly is also discussed. RESULTS: Four primary etiologies are described for
      postsynaptic neuron damage leading to a centrally acting monoamine relative
      nutritional deficiency, all of which require monoamine transporter optimization
      to define the proper amino acid dosing values of serotonin and dopamine
      precursors. CONCLUSION: Humans suffering from chronic centrally acting monoamine
      related disease are not suffering from a drug deficiency; they are suffering from
      a relative nutritional deficiency involving serotonin and dopamine amino acid
      precursors. Whenever low or inadequate levels of monoamine neurotransmitters
      exist, a relative nutritional deficiency is present. These precursors must be
      administered simultaneously under the guidance of monoamine transporter
      optimization in order to achieve optimal relative nutritional deficiency
      management. Improper administration of these precursors can exacerbate and/or
      facilitate new onset of centrally acting monoamine-related relative nutritional
      deficiencies.

PMID- 22615538
TI  - Postural control in children with typical development and children with profound
      hearing loss.
AB  - PURPOSE: To describe the behavior of the postural control in children with
      profound sensorineural hearing loss and compare the results of experimental tests
      with hearing children aged 7 to 10 years. PATIENTS AND METHODS: This is a cross
      sectional study where 100 children were divided into experimental and control
      groups. We used a force platform, AccuSway Plus, where the tests were conducted
      under the experimental conditions: open base, eyes open (OBEO); open base, eyes
      closed (OBEC); closed base, eyes open (CBEO); closed base, eyes closed (CBEC).
      The body sway velocity (V) of the center of pressure, the displacement in the
      anteroposterior direction (COPap) and mediolateral (COPml) of the center of
      pressure were the parameters to evaluate the postural control. For statistical
      analysis we used the nonparametric Mann-Whitney U test, with a significance level
      of 5%. RESULTS: In comparisons of variables between the groups, the experimental
      group outperformed by at least 75% of the control group values. In terms of
      global trends, the experimental group shows higher values of body oscillations in
      all experimental conditions and variables evaluated. Children with hearing loss
      had poorer balance performance compared to the group of hearing. The inferential
      analysis revealed a statistically significant difference in the balance between
      deaf and hearing children in the OBEC experimental condition in relation to the
      COPml parameter (P = 0.04). There were no statistically significant differences
      in comparisons between the sexes when the groups were analyzed separately. The
      prevalence of unknown etiology showed 58% of cases and congenital rubella in 16%.
      The discovery of deafness occurred in 70% of children before the age of 3 years.
      CONCLUSION: In this study, children with hearing loss had poorer balance
      performance compared to the group of hearing children. This finding confirms the
      need to investigate postural control through longitudinal studies to identify the
      area of sensory deficit causing poor balance performance and promote more
      specific early interventions.

PMID- 22615539
TI  - Biological diversity of the Minnesota caddisflies (Insecta, Trichoptera).
AB  - The caddisfly fauna of Minnesota contains at least 277 species within 21 families
      and 75 genera. These species are based on examination of 312,884 specimens from
      2,166 collections of 937 Minnesota aquatic habitats from 1890 to 2007. Included
      in these totals is my own quantitative sampling of 4 representative habitat
      types: small streams, medium rivers, large rivers, and lakes, from each of the 58
      major Minnesota watersheds from June through September during 1999-2001. All
      species are illustrated herein, and their known Minnesota abundances,
      distributions, adult flight periodicities, and habitat affinities presented. Four
      species: Lepidostoma griseum (Lepidostomatidae), Psilotreta indecisa
      (Odontoceridae), and Phryganea sayi and Ptilostomis angustipennis (Phryganeidae)
      are added to the known fauna. An additional 31 dubious species records are
      removed for various reasons. Of the 5 determined caddisfly regions of the state,
      species richness per watershed was highest in the Lake Superior and Northern
      Regions, intermediate in the Southeastern, and lowest in the Northwestern and
      Southern. Of the 48 individual collections that yielded >40 species, all but 1
      were from the Northern Region. Many species, especially within the families
      Limnephilidae and Phryganeidae, have appeared to decrease in distribution and
      abundance during the past 75 years, particularly those once common within the
      Northwestern and Southern Regions. Many species now appear regionally extirpated,
      and a few have disappeared from the entire state. The loss of species in the
      Northwestern and Southern Regions, and probably elsewhere, is almost certainly
      related to the conversion of many habitats to large-scale agriculture during the
      mid-20th century.

PMID- 22615540
TI  - Mechanisms and evolutionary patterns of mammalian and avian dosage compensation.
AB  - As a result of sex chromosome differentiation from ancestral autosomes, male
      mammalian cells only contain one X chromosome. It has long been hypothesized that
      X-linked gene expression levels have become doubled in males to restore the
      original transcriptional output, and that the resulting X overexpression in
      females then drove the evolution of X inactivation (XCI). However, this model has
      never been directly tested and patterns and mechanisms of dosage compensation
      across different mammals and birds generally remain little understood. Here we
      trace the evolution of dosage compensation using extensive transcriptome data
      from males and females representing all major mammalian lineages and birds. Our
      analyses suggest that the X has become globally upregulated in marsupials,
      whereas we do not detect a global upregulation of this chromosome in placental
      mammals. However, we find that a subset of autosomal genes interacting with X
      linked genes have become downregulated in placentals upon the emergence of sex
      chromosomes. Thus, different driving forces may underlie the evolution of XCI and
      the highly efficient equilibration of X expression levels between the sexes
      observed for both of these lineages. In the egg-laying monotremes and birds,
      which have partially homologous sex chromosome systems, partial upregulation of
      the X (Z in birds) evolved but is largely restricted to the heterogametic sex,
      which provides an explanation for the partially sex-biased X (Z) expression and
      lack of global inactivation mechanisms in these lineages. Our findings suggest
      that dosage reductions imposed by sex chromosome differentiation events in
      amniotes were resolved in strikingly different ways.

PMID- 22615541
TI  - Species interactions alter evolutionary responses to a novel environment.
AB  - Studies of evolutionary responses to novel environments typically consider single
      species or perhaps pairs of interacting species. However, all organisms co-occur
      with many other species, resulting in evolutionary dynamics that might not match
      those predicted using single species approaches. Recent theories predict that
      species interactions in diverse systems can influence how component species
      evolve in response to environmental change. In turn, evolution might have
      consequences for ecosystem functioning. We used experimental communities of five
      bacterial species to show that species interactions have a major impact on
      adaptation to a novel environment in the laboratory. Species in communities
      diverged in their use of resources compared with the same species in monocultures
      and evolved to use waste products generated by other species. This generally led
      to a trade-off between adaptation to the abiotic and biotic components of the
      environment, such that species evolving in communities had lower growth rates
      when assayed in the absence of other species. Based on growth assays and on
      nuclear magnetic resonance (NMR) spectroscopy of resource use, all species
      evolved more in communities than they did in monocultures. The evolutionary
      changes had significant repercussions for the functioning of these experimental
      ecosystems: communities reassembled from isolates that had evolved in polyculture
      were more productive than those reassembled from isolates that had evolved in
      monoculture. Our results show that the way in which species adapt to new
      environments depends critically on the biotic environment of co-occurring
      species. Moreover, predicting how functioning of complex ecosystems will respond
      to an environmental change requires knowing how species interactions will evolve.

PMID- 22615542
TI  - Adaptive evolution in ecological communities.
AB  - Understanding how natural selection drives evolution is a key challenge in
      evolutionary biology. Most studies of adaptation focus on how a single
      environmental factor, such as increased temperature, affects evolution within a
      single species. The biological relevance of these experiments is limited because
      nature is infinitely more complex. Most species are embedded within communities
      containing many species that interact with one another and the physical
      environment. To understand the evolutionary significance of such ecological
      complexity, experiments must test the evolutionary impact of interactions among
      multiple species during adaptation. Here we highlight an experiment that
      manipulates species composition and tracks evolutionary responses within each
      species, while testing for the mechanisms by which species interact and adapt to
      their environment. We also discuss limitations of previous studies of adaptive
      evolution and emphasize how an experimental evolution approach can circumvent
      such shortcomings. Understanding how community composition acts as a selective
      force will improve our ability to predict how species adapt to natural and human
      induced environmental change.

PMID- 22615544
TI  - Innovation and access to medicines for neglected populations: could a treaty
      address a broken pharmaceutical R&D system?

PMID- 22615545
TI  - A new deal for global health R&D? The recommendations of the Consultative Expert
      Working Group on Research and Development (CEWG).

PMID- 22615546
TI  - A spatial model of mosquito host-seeking behavior.
AB  - Mosquito host-seeking behavior and heterogeneity in host distribution are
      important factors in predicting the transmission dynamics of mosquito-borne
      infections such as dengue fever, malaria, chikungunya, and West Nile virus. We
      develop and analyze a new mathematical model to describe the effect of spatial
      heterogeneity on the contact rate between mosquito vectors and hosts. The model
      includes odor plumes generated by spatially distributed hosts, wind velocity, and
      mosquito behavior based on both the prevailing wind and the odor plume. On a
      spatial scale of meters and a time scale of minutes, we compare the effectiveness
      of different plume-finding and plume-tracking strategies that mosquitoes could
      use to locate a host. The results show that two different models of chemotaxis
      are capable of producing comparable results given appropriate parameter choices
      and that host finding is optimized by a strategy of flying across the wind until
      the odor plume is intercepted. We also assess the impact of changing the level of
      host aggregation on mosquito host-finding success near the end of the host
      seeking flight. When clusters of hosts are more tightly associated on smaller
      patches, the odor plume is narrower and the biting rate per host is decreased.
      For two host groups of unequal number but equal spatial density, the biting rate
      per host is lower in the group with more individuals, indicative of an attack
      abatement effect of host aggregation. We discuss how this approach could assist
      parameter choices in compartmental models that do not explicitly model the
      spatial arrangement of individuals and how the model could address larger spatial
      scales and other probability models for mosquito behavior, such as Levy
      distributions.

PMID- 22615547
TI  - Insights into the fold organization of TIM barrel from interaction energy based
      structure networks.
AB  - There are many well-known examples of proteins with low sequence similarity,
      adopting the same structural fold. This aspect of sequence-structure relationship
      has been extensively studied both experimentally and theoretically, however with
      limited success. Most of the studies consider remote homology or "sequence
      conservation" as the basis for their understanding. Recently "interaction energy"
      based network formalism (Protein Energy Networks (PENs)) was developed to
      understand the determinants of protein structures. In this paper we have used
      these PENs to investigate the common non-covalent interactions and their
      collective features which stabilize the TIM barrel fold. We have also developed a
      method of aligning PENs in order to understand the spatial conservation of
      interactions in the fold. We have identified key common interactions responsible
      for the conservation of the TIM fold, despite high sequence dissimilarity. For
      instance, the central beta barrel of the TIM fold is stabilized by long-range
      high energy electrostatic interactions and low-energy contiguous vdW interactions
      in certain families. The other interfaces like the helix-sheet or the helix-helix
      seem to be devoid of any high energy conserved interactions. Conserved
      interactions in the loop regions around the catalytic site of the TIM fold have
      also been identified, pointing out their significance in both structural and
      functional evolution. Based on these investigations, we have developed a novel
      network based phylogenetic analysis for remote homologues, which can perform
      better than sequence based phylogeny. Such an analysis is more meaningful from
      both structural and functional evolutionary perspective. We believe that the
      information obtained through the "interaction conservation" viewpoint and the
      subsequently developed method of structure network alignment, can shed new light
      in the fields of fold organization and de novo computational protein design.

PMID- 22615548
TI  - Optimal control of saccades by spatial-temporal activity patterns in the monkey
      superior colliculus.
AB  - A major challenge in computational neurobiology is to understand how populations
      of noisy, broadly-tuned neurons produce accurate goal-directed actions such as
      saccades. Saccades are high-velocity eye movements that have stereotyped,
      nonlinear kinematics; their duration increases with amplitude, while peak eye
      velocity saturates for large saccades. Recent theories suggest that these
      characteristics reflect a deliberate strategy that optimizes a speed-accuracy
      tradeoff in the presence of signal-dependent noise in the neural control signals.
      Here we argue that the midbrain superior colliculus (SC), a key sensorimotor
      interface that contains a topographically-organized map of saccade vectors, is in
      an ideal position to implement such an optimization principle. Most models
      attribute the nonlinear saccade kinematics to saturation in the brainstem pulse
      generator downstream from the SC. However, there is little data to support this
      assumption. We now present new neurophysiological evidence for an alternative
      scheme, which proposes that these properties reside in the spatial-temporal
      dynamics of SC activity. As predicted by this scheme, we found a remarkably
      systematic organization in the burst properties of saccade-related neurons along
      the rostral-to-caudal (i.e., amplitude-coding) dimension of the SC motor map:
      peak firing-rates systematically decrease for cells encoding larger saccades,
      while burst durations and skewness increase, suggesting that this spatial
      gradient underlies the increase in duration and skewness of the eye velocity
      profiles with amplitude. We also show that all neurons in the recruited
      population synchronize their burst profiles, indicating that the burst-timing of
      each cell is determined by the planned saccade vector in which it participates,
      rather than by its anatomical location. Together with the observation that
      saccade-related SC cells indeed show signal-dependent noise, this precisely tuned
      organization of SC burst activity strongly supports the notion of an optimal
      motor-control principle embedded in the SC motor map as it fully accounts for the
      straight trajectories and kinematic nonlinearity of saccades.

PMID- 22615549
TI  - Google goes cancer: improving outcome prediction for cancer patients by network
      based ranking of marker genes.
AB  - Predicting the clinical outcome of cancer patients based on the expression of
      marker genes in their tumors has received increasing interest in the past decade.
      Accurate predictors of outcome and response to therapy could be used to
      personalize and thereby improve therapy. However, state of the art methods used
      so far often found marker genes with limited prediction accuracy, limited
      reproducibility, and unclear biological relevance. To address this problem, we
      developed a novel computational approach to identify genes prognostic for outcome
      that couples gene expression measurements from primary tumor samples with a
      network of known relationships between the genes. Our approach ranks genes
      according to their prognostic relevance using both expression and network
      information in a manner similar to Google's PageRank. We applied this method to
      gene expression profiles which we obtained from 30 patients with pancreatic
      cancer, and identified seven candidate marker genes prognostic for outcome.
      Compared to genes found with state of the art methods, such as Pearson
      correlation of gene expression with survival time, we improve the prediction
      accuracy by up to 7%. Accuracies were assessed using support vector machine
      classifiers and Monte Carlo cross-validation. We then validated the prognostic
      value of our seven candidate markers using immunohistochemistry on an independent
      set of 412 pancreatic cancer samples. Notably, signatures derived from our
      candidate markers were independently predictive of outcome and superior to
      established clinical prognostic factors such as grade, tumor size, and nodal
      status. As the amount of genomic data of individual tumors grows rapidly, our
      algorithm meets the need for powerful computational approaches that are key to
      exploit these data for personalized cancer therapies in clinical practice.

PMID- 22615550
TI  - Mechanical stress inference for two dimensional cell arrays.
AB  - Many morphogenetic processes involve mechanical rearrangements of epithelial
      tissues that are driven by precisely regulated cytoskeletal forces and cell
      adhesion. The mechanical state of the cell and intercellular adhesion are not
      only the targets of regulation, but are themselves the likely signals that
      coordinate developmental process. Yet, because it is difficult to directly
      measure mechanical stress in vivo on sub-cellular scale, little is understood
      about the role of mechanics in development. Here we present an alternative
      approach which takes advantage of the recent progress in live imaging of
      morphogenetic processes and uses computational analysis of high resolution images
      of epithelial tissues to infer relative magnitude of forces acting within and
      between cells. We model intracellular stress in terms of bulk pressure and
      interfacial tension, allowing these parameters to vary from cell to cell and from
      interface to interface. Assuming that epithelial cell layers are close to
      mechanical equilibrium, we use the observed geometry of the two dimensional cell
      array to infer interfacial tensions and intracellular pressures. Here we present
      the mathematical formulation of the proposed Mechanical Inverse method and apply
      it to the analysis of epithelial cell layers observed at the onset of ventral
      furrow formation in the Drosophila embryo and in the process of hair-cell
      determination in the avian cochlea. The analysis reveals mechanical anisotropy in
      the former process and mechanical heterogeneity, correlated with cell
      differentiation, in the latter process. The proposed method opens a way for
      quantitative and detailed experimental tests of models of cell and tissue
      mechanics.

PMID- 22615551
TI  - Resolving the ortholog conjecture: orthologs tend to be weakly, but
      significantly, more similar in function than paralogs.
AB  - The function of most proteins is not determined experimentally, but is
      extrapolated from homologs. According to the "ortholog conjecture", or standard
      model of phylogenomics, protein function changes rapidly after duplication,
      leading to paralogs with different functions, while orthologs retain the
      ancestral function. We report here that a comparison of experimentally supported
      functional annotations among homologs from 13 genomes mostly supports this model.
      We show that to analyze GO annotation effectively, several confounding factors
      need to be controlled: authorship bias, variation of GO term frequency among
      species, variation of background similarity among species pairs, and propagated
      annotation bias. After controlling for these biases, we observe that orthologs
      have generally more similar functional annotations than paralogs. This is
      especially strong for sub-cellular localization. We observe only a weak decrease
      in functional similarity with increasing sequence divergence. These findings hold
      over a large diversity of species; notably orthologs from model organisms such as
      E. coli, yeast or mouse have conserved function with human proteins.

PMID- 22615543
TI  - Pregnancy and infant outcomes among HIV-infected women taking long-term ART with
      and without tenofovir in the DART trial.
AB  - BACKGROUND: Few data have described long-term outcomes for infants born to HIV
      infected African women taking antiretroviral therapy (ART) in pregnancy. This is
      particularly true for World Health Organization (WHO)-recommended tenofovir
      containing first-line regimens, which are increasingly used and known to cause
      renal and bone toxicities; concerns have been raised about potential toxicity in
      babies due to in utero tenofovir exposure. METHODS AND FINDINGS: Pregnancy
      outcome and maternal/infant ART were collected in Ugandan/Zimbabwean HIV-infected
      women initiating ART during The Development of AntiRetroviral Therapy in Africa
      (DART) trial, which compared routine laboratory monitoring (CD4; toxicity) versus
      clinically driven monitoring. Women were followed 15 January 2003 to 28 September
      2009. Infant feeding, clinical status, and biochemistry/haematology results were
      collected in a separate infant study. Effect of in utero ART exposure on infant
      growth was analysed using random effects models. 382 pregnancies occurred in
      302/1,867 (16%) women (4.4/100 woman-years [95% CI 4.0-4.9]). 226/390 (58%)
      outcomes were live-births, 27 (7%) stillbirths (>=22 wk), and 137 (35%)
      terminations/miscarriages (<22 wk). Of 226 live-births, seven (3%) infants died
      <2 wk from perinatal causes and there were seven (3%) congenital abnormalities,
      with no effect of in utero tenofovir exposure (p>0.4). Of 219 surviving infants,
      182 (83%) enrolled in the follow-up study; median (interquartile range [IQR]) age
      at last visit was 25 (12-38) months. From mothers' ART, 62/9/111 infants had
      no/20%-89%/>=90% in utero tenofovir exposure; most were also
      zidovudine/lamivudine exposed. All 172 infants tested were HIV-negative (ten
      untested). Only 73/182(40%) infants were breast-fed for median 94 (IQR 75-212)
      days. Overall, 14 infants died at median (IQR) age 9 (3-23) months, giving 5% 12
      month mortality; six of 14 were HIV-uninfected; eight untested infants died of
      respiratory infection (three), sepsis (two), burns (one), measles (one), unknown
      (one). During follow-up, no bone fractures were reported to have occurred; 12/368
      creatinines and seven out of 305 phosphates were grade one (16) or two (three) in
      14 children with no effect of in utero tenofovir (p>0.1). There was no evidence
      that in utero tenofovir affected growth after 2 years (p = 0.38). Attained height
      and weight for age were similar to general (HIV-uninfected) Ugandan populations.
      Study limitations included relatively small size and lack of randomisation to
      maternal ART regimens. CONCLUSIONS: Overall 1-year 5% infant mortality was
      similar to the 2%-4% post-neonatal mortality observed in this region. No increase
      in congenital, renal, or growth abnormalities was observed with in utero
      tenofovir exposure. Although some infants died untested, absence of recorded HIV
      infection with combination ART in pregnancy is encouraging. Detailed safety of
      tenofovir for pre-exposure prophylaxis will need confirmation from longer term
      follow-up of larger numbers of exposed children. TRIAL REGISTRATION:
      www.controlled-trials.com ISRCTN13968779

PMID- 22615552
TI  - Proteome sampling by the HLA class I antigen processing pathway.
AB  - The peptide repertoire that is presented by the set of HLA class I molecules of
      an individual is formed by the different players of the antigen processing
      pathway and the stringent binding environment of the HLA class I molecules.
      Peptide elution studies have shown that only a subset of the human proteome is
      sampled by the antigen processing machinery and represented on the cell surface.
      In our study, we quantified the role of each factor relevant in shaping the HLA
      class I peptide repertoire by combining peptide elution data, in silico
      predictions of antigen processing and presentation, and data on gene expression
      and protein abundance. Our results indicate that gene expression level, protein
      abundance, and rate of potential binding peptides per protein have a clear impact
      on sampling probability. Furthermore, once a protein is available for the antigen
      processing machinery in sufficient amounts, C-terminal processing efficiency and
      binding affinity to the HLA class I molecule determine the identity of the
      presented peptides. Having studied the impact of each of these factors
      separately, we subsequently combined all factors in a logistic regression model
      in order to quantify their relative impact. This model demonstrated the
      superiority of protein abundance over gene expression level in predicting
      sampling probability. Being able to discriminate between sampled and non-sampled
      proteins to a significant degree, our approach can potentially be used to predict
      the sampling probability of self proteins and of pathogen-derived proteins, which
      is of importance for the identification of autoimmune antigens and vaccination
      targets.

PMID- 22615553
TI  - Reconstruction of genome-scale active metabolic networks for 69 human cell types
      and 16 cancer types using INIT.
AB  - Development of high throughput analytical methods has given physicians the
      potential access to extensive and patient-specific data sets, such as gene
      sequences, gene expression profiles or metabolite footprints. This opens for a
      new approach in health care, which is both personalized and based on system-level
      analysis. Genome-scale metabolic networks provide a mechanistic description of
      the relationships between different genes, which is valuable for the analysis and
      interpretation of large experimental data-sets. Here we describe the generation
      of genome-scale active metabolic networks for 69 different cell types and 16
      cancer types using the INIT (Integrative Network Inference for Tissues)
      algorithm. The INIT algorithm uses cell type specific information about protein
      abundances contained in the Human Proteome Atlas as the main source of evidence.
      The generated models constitute the first step towards establishing a Human
      Metabolic Atlas, which will be a comprehensive description (accessible online) of
      the metabolism of different human cell types, and will allow for tissue-level and
      organism-level simulations in order to achieve a better understanding of complex
      diseases. A comparative analysis between the active metabolic networks of cancer
      types and healthy cell types allowed for identification of cancer-specific
      metabolic features that constitute generic potential drug targets for cancer
      treatment.

PMID- 22615554
TI  - The layer-oriented approach to declarative languages for biological modeling.
AB  - We present a new approach to modeling languages for computational biology, which
      we call the layer-oriented approach. The approach stems from the observation that
      many diverse biological phenomena are described using a small set of mathematical
      formalisms (e.g. differential equations), while at the same time different
      domains and subdomains of computational biology require that models are
      structured according to the accepted terminology and classification of that
      domain. Our approach uses distinct semantic layers to represent the domain
      specific biological concepts and the underlying mathematical formalisms.
      Additional functionality can be transparently added to the language by adding
      more layers. This approach is specifically concerned with declarative languages,
      and throughout the paper we note some of the limitations inherent to declarative
      approaches. The layer-oriented approach is a way to specify explicitly how high
      level biological modeling concepts are mapped to a computational representation,
      while abstracting away details of particular programming languages and simulation
      environments. To illustrate this process, we define an example language for
      describing models of ionic currents, and use a general mathematical notation for
      semantic transformations to show how to generate model simulation code for
      various simulation environments. We use the example language to describe a
      Purkinje neuron model and demonstrate how the layer-oriented approach can be used
      for solving several practical issues of computational neuroscience model
      development. We discuss the advantages and limitations of the approach in
      comparison with other modeling language efforts in the domain of computational
      biology and outline some principles for extensible, flexible modeling language
      design. We conclude by describing in detail the semantic transformations defined
      for our language.

PMID- 22615555
TI  - Emergence of a small-world functional network in cultured neurons.
AB  - The functional networks of cultured neurons exhibit complex network properties
      similar to those found in vivo. Starting from random seeding, cultures undergo
      significant reorganization during the initial period in vitro, yet despite
      providing an ideal platform for observing developmental changes in neuronal
      connectivity, little is known about how a complex functional network evolves from
      isolated neurons. In the present study, evolution of functional connectivity was
      estimated from correlations of spontaneous activity. Network properties were
      quantified using complex measures from graph theory and used to compare cultures
      at different stages of development during the first 5 weeks in vitro. Networks
      obtained from young cultures (14 days in vitro) exhibited a random topology,
      which evolved to a small-world topology during maturation. The topology change
      was accompanied by an increased presence of highly connected areas (hubs) and
      network efficiency increased with age. The small-world topology balances
      integration of network areas with segregation of specialized processing units.
      The emergence of such network structure in cultured neurons, despite a lack of
      external input, points to complex intrinsic biological mechanisms. Moreover, the
      functional network of cultures at mature ages is efficient and highly suited to
      complex processing tasks.

PMID- 22615556
TI  - Network topologies and dynamics leading to endotoxin tolerance and priming in
      innate immune cells.
AB  - The innate immune system, acting as the first line of host defense, senses and
      adapts to foreign challenges through complex intracellular and intercellular
      signaling networks. Endotoxin tolerance and priming elicited by macrophages are
      classic examples of the complex adaptation of innate immune cells. Upon
      repetitive exposures to different doses of bacterial endotoxin
      (lipopolysaccharide) or other stimulants, macrophages show either suppressed or
      augmented inflammatory responses compared to a single exposure to the stimulant.
      Endotoxin tolerance and priming are critically involved in both immune
      homeostasis and the pathogenesis of diverse inflammatory diseases. However, the
      underlying molecular mechanisms are not well understood. By means of a
      computational search through the parameter space of a coarse-grained three-node
      network with a two-stage Metropolis sampling approach, we enumerated all the
      network topologies that can generate priming or tolerance. We discovered three
      major mechanisms for priming (pathway synergy, suppressor deactivation, activator
      induction) and one for tolerance (inhibitor persistence). These results not only
      explain existing experimental observations, but also reveal intriguing test
      scenarios for future experimental studies to clarify mechanisms of endotoxin
      priming and tolerance.

PMID- 22615558
TI  - Influence of microbiota on viral infections.

PMID- 22615557
TI  - Lysogeny with Shiga toxin 2-encoding bacteriophages represses type III secretion
      in enterohemorrhagic Escherichia coli.
AB  - Lytic or lysogenic infections by bacteriophages drive the evolution of enteric
      bacteria. Enterohemorrhagic Escherichia coli (EHEC) have recently emerged as a
      significant zoonotic infection of humans with the main serotypes carried by
      ruminants. Typical EHEC strains are defined by the expression of a type III
      secretion (T3S) system, the production of Shiga toxins (Stx) and association with
      specific clinical symptoms. The genes for Stx are present on lambdoid
      bacteriophages integrated into the E. coli genome. Phage type (PT) 21/28 is the
      most prevalent strain type linked with human EHEC infections in the United
      Kingdom and is more likely to be associated with cattle shedding high levels of
      the organism than PT32 strains. In this study we have demonstrated that the
      majority (90%) of PT 21/28 strains contain both Stx2 and Stx2c phages,
      irrespective of source. This is in contrast to PT 32 strains for which only a
      minority of strains contain both Stx2 and 2c phages (28%). PT21/28 strains had a
      lower median level of T3S compared to PT32 strains and so the relationship
      between Stx phage lysogeny and T3S was investigated. Deletion of Stx2 phages from
      EHEC strains increased the level of T3S whereas lysogeny decreased T3S. This
      regulation was confirmed in an E. coli K12 background transduced with a marked
      Stx2 phage followed by measurement of a T3S reporter controlled by induced levels
      of the LEE-encoded regulator (Ler). The presence of an integrated Stx2 phage was
      shown to repress Ler induction of LEE1 and this regulation involved the CII phage
      regulator. This repression could be relieved by ectopic expression of a cognate
      CI regulator. A model is proposed in which Stx2-encoding bacteriophages regulate
      T3S to co-ordinate epithelial cell colonisation that is promoted by Stx and
      secreted effector proteins.

PMID- 22615559
TI  - Pdl1 is a putative lipase that enhances Photorhabdus toxin complex secretion.
AB  - The Toxin Complex (TC) is a large multi-subunit toxin first characterized in the
      insect pathogens Photorhabdus and Xenorhabdus, but now seen in a range of
      pathogens, including those of humans. These complexes comprise three protein
      subunits, A, B and C which in the Xenorhabdus toxin are found in a 4:1:1
      stoichiometry. Some TCs have been demonstrated to exhibit oral toxicity to
      insects and have the potential to be developed as a pest control technology. The
      lack of recognisable signal sequences in the three large component proteins
      hinders an understanding of their mode of secretion. Nevertheless, we have shown
      the Photorhabdus luminescens (Pl) Tcd complex has been shown to associate with
      the bacteria's surface, although some strains can also release it into the
      surrounding milieu. The large number of tc gene homologues in Pl make study of
      the export process difficult and as such we have developed and validated a
      heterologous Escherichia coli expression model to study the release of these
      important toxins. In addition to this model, we have used comparative genomics
      between a strain that releases high levels of Tcd into the supernatant and one
      that retains the toxin on its surface, to identify a protein responsible for
      enhancing secretion and release of these toxins. This protein is a putative
      lipase (Pdl1) which is regulated by a small tightly linked antagonist protein
      (Orf53). The identification of homologues of these in other bacteria, linked to
      other virulence factor operons, such as type VI secretion systems, suggests that
      these genes represent a general and widespread mechanism for enhancing toxin
      release in gram negative pathogens.

PMID- 22615560
TI  - ATG5 is essential for ATG8-dependent autophagy and mitochondrial homeostasis in
      Leishmania major.
AB  - Macroautophagy has been shown to be important for the cellular remodelling
      required for Leishmania differentiation. We now demonstrate that L. major
      contains a functional ATG12-ATG5 conjugation system, which is required for ATG8
      dependent autophagosome formation. Nascent autophagosomes were found commonly
      associated with the mitochondrion. L. major mutants lacking ATG5 (Deltaatg5) were
      viable as promastigotes but were unable to form autophagosomes, had morphological
      abnormalities including a much reduced flagellum, were less able to differentiate
      and had greatly reduced virulence to macrophages and mice. Analyses of the lipid
      metabolome of Deltaatg5 revealed marked elevation of phosphatidylethanolamines
      (PE) in comparison to wild type parasites. The Deltaatg5 mutants also had
      increased mitochondrial mass but reduced mitochondrial membrane potential and
      higher levels of reactive oxygen species. These findings indicate that the lack
      of ATG5 and autophagy leads to perturbation of the phospholipid balance in the
      mitochondrion, possibly through ablation of membrane use and conjugation of
      mitochondrial PE to ATG8 for autophagosome biogenesis, resulting in a
      dysfunctional mitochondrion with impaired oxidative ability and energy
      generation. The overall result of this is reduced virulence.

PMID- 22615562
TI  - miR-27b targets KSRP to coordinate TLR4-mediated epithelial defense against
      Cryptosporidium parvum infection.
AB  - Cryptosporidium is a protozoan parasite that infects the gastrointestinal
      epithelium and causes a diarrheal disease. Toll-like receptor (TLR)- and NF
      kappaB-mediated immune responses from epithelial cells, such as production of
      antimicrobial peptides and generation of reactive nitrogen species, are important
      components of the host's defense against cryptosporidial infection. Here we
      report data demonstrating a role for miR-27b in the regulation of TLR4/NF-kappaB
      mediated epithelial anti-Cryptosporidium parvum responses. We found that C.
      parvum infection induced nitric oxide (NO) production in host epithelial cells in
      a TLR4/NF-kappaB-dependent manner, with the involvement of the stabilization of
      inducible NO synthase (iNOS) mRNA. C. parvum infection of epithelial cells
      activated NF-kappaB signaling to increase transcription of the miR-27b gene.
      Meanwhile, downregulation of KH-type splicing regulatory protein (KSRP) was
      detected in epithelial cells following C. parvum infection. Importantly, miR-27b
      targeted the 3'-untranslated region of KSRP, resulting in translational
      suppression. C. parvum infection decreased KSRP expression through upregulating
      miR-27b. Functional manipulation of KSRP or miR-27b caused reciprocal alterations
      in iNOS mRNA stability in infected cells. Forced expression of KSRP and
      inhibition of miR-27b resulted in an increased burden of C. parvum infection.
      Downregulation of KSRP through upregulating miR-27b was also detected in
      epithelial cells following LPS stimulation. These data suggest that miR-27b
      targets KSRP and modulates iNOS mRNA stability following C. parvum infection, a
      process that may be relevant to the regulation of epithelial anti-microbial
      defense in general.

PMID- 22615561
TI  - Pathogen-induced proapoptotic phenotype and high CD95 (Fas) expression accompany
      a suboptimal CD8+ T-cell response: reversal by adenoviral vaccine.
AB  - MHC class Ia-restricted CD8(+) T cells are important mediators of the adaptive
      immune response against infections caused by intracellular microorganisms.
      Whereas antigen-specific effector CD8(+) T cells can clear infection caused by
      intracellular pathogens, in some circumstances, the immune response is suboptimal
      and the microorganisms survive, causing host death or chronic infection. Here, we
      explored the cellular and molecular mechanisms that could explain why CD8(+) T
      cell-mediated immunity during infection with the human protozoan parasite
      Trypanosoma cruzi is not optimal. For that purpose, we compared the CD8(+) T-cell
      mediated immune responses in mice infected with T. cruzi or vaccinated with a
      recombinant adenovirus expressing an immunodominant parasite antigen. Several
      functional and phenotypic characteristics of specific CD8(+) T cells overlapped.
      Among few exceptions was an accelerated expansion of the immune response in
      adenoviral vaccinated mice when compared to infected ones. Also, there was an
      upregulated expression of the apoptotic-signaling receptor CD95 on the surface of
      specific T cells from infected mice, which was not observed in the case of
      adenoviral-vaccinated mice. Most importantly, adenoviral vaccine provided at the
      time of infection significantly reduced the upregulation of CD95 expression and
      the proapoptotic phenotype of pathogen-specific CD8(+) cells expanded during
      infection. In parallel, infected adenovirus-vaccinated mice had a stronger CD8 T
      cell mediated immune response and survived an otherwise lethal infection. We
      concluded that a suboptimal CD8(+) T-cell response is associated with an
      upregulation of CD95 expression and a proapoptotic phenotype. Both can be blocked
      by adenoviral vaccination.

PMID- 22615563
TI  - The ubiquitin/proteasome system mediates entry and endosomal trafficking of
      Kaposi's sarcoma-associated herpesvirus in endothelial cells.
AB  - Ubiquitination, a post-translational modification, mediates diverse cellular
      functions including endocytic transport of molecules. Kaposi's sarcoma-associated
      herpesvirus (KSHV), an enveloped herpesvirus, enters endothelial cells primarily
      through clathrin-mediated endocytosis. Whether ubiquitination and proteasome
      activity regulates KSHV entry and endocytosis remains unknown. We showed that
      inhibition of proteasome activity reduced KSHV entry into endothelial cells and
      intracellular trafficking to nuclei, thus preventing KSHV infection of the cells.
      Three-dimensional (3-D) analyses revealed accumulation of KSHV particles in a
      cytoplasmic compartment identified as EEA1+ endosomal vesicles upon proteasome
      inhibition. KSHV particles are colocalized with ubiquitin-binding proteins epsin
      and eps15. Furthermore, ubiquitination mediates internalization of both KSHV and
      one of its receptors integrin beta1. KSHV particles are colocalized with
      activated forms of the E3 ligase c-Cbl. Knock-down of c-Cbl or inhibition of its
      phosphorylation reduced viral entry and intracellular trafficking, resulting in
      decreased KSHV infectivity. These results demonstrate that ubiquitination
      mediates internalization of both KSHV and one of its cognate receptors integrin
      beta1, and identify c-Cbl as a potential E3 ligase that facilitates this process.

PMID- 22615564
TI  - The EBV immunoevasins vIL-10 and BNLF2a protect newly infected B cells from
      immune recognition and elimination.
AB  - Lifelong persistence of Epstein-Barr virus (EBV) in infected hosts is mainly owed
      to the virus' pronounced abilities to evade immune responses of its human host.
      Active immune evasion mechanisms reduce the immunogenicity of infected cells and
      are known to be of major importance during lytic infection. The EBV genes BCRF1
      and BNLF2a encode the viral homologue of IL-10 (vIL-10) and an inhibitor of the
      transporter associated with antigen processing (TAP), respectively. Both are
      known immunoevasins in EBV's lytic phase. Here we describe that BCRF1 and BNLF2a
      are functionally expressed instantly upon infection of primary B cells. Using EBV
      mutants deficient in BCRF1 and BNLF2a, we show that both factors contribute to
      evading EBV-specific immune responses during the earliest phase of infection. vIL
      10 impairs NK cell mediated killing of infected B cells, interferes with CD4+ T
      cell activity, and modulates cytokine responses, while BNLF2a reduces antigen
      presentation and recognition of newly infected cells by EBV-specific CD8+ T
      cells. Together, both factors significantly diminish the immunogenicity of EBV
      infected cells during the initial, pre-latent phase of infection and may improve
      the establishment of a latent EBV infection in vivo.

PMID- 22615566
TI  - Plasticity of the beta-trefoil protein fold in the recognition and control of
      invertebrate predators and parasites by a fungal defence system.
AB  - Discrimination between self and non-self is a prerequisite for any defence
      mechanism; in innate defence, this discrimination is often mediated by lectins
      recognizing non-self carbohydrate structures and so relies on an arsenal of host
      lectins with different specificities towards target organism carbohydrate
      structures. Recently, cytoplasmic lectins isolated from fungal fruiting bodies
      have been shown to play a role in the defence of multicellular fungi against
      predators and parasites. Here, we present a novel fruiting body lectin, CCL2,
      from the ink cap mushroom Coprinopsis cinerea. We demonstrate the toxicity of the
      lectin towards Caenorhabditis elegans and Drosophila melanogaster and present its
      NMR solution structure in complex with the trisaccharide,
      GlcNAcbeta1,4[Fucalpha1,3]GlcNAc, to which it binds with high specificity and
      affinity in vitro. The structure reveals that the monomeric CCL2 adopts a beta
      trefoil fold and recognizes the trisaccharide by a single, topologically novel
      carbohydrate-binding site. Site-directed mutagenesis of CCL2 and identification
      of C. elegans mutants resistant to this lectin show that its nematotoxicity is
      mediated by binding to alpha1,3-fucosylated N-glycan core structures of nematode
      glycoproteins; feeding with fluorescently labeled CCL2 demonstrates that these
      target glycoproteins localize to the C. elegans intestine. Since the identified
      glycoepitope is characteristic for invertebrates but absent from fungi, our data
      show that the defence function of fruiting body lectins is based on the specific
      recognition of non-self carbohydrate structures. The trisaccharide specifically
      recognized by CCL2 is a key carbohydrate determinant of pollen and insect venom
      allergens implying this particular glycoepitope is targeted by both fungal
      defence and mammalian immune systems. In summary, our results demonstrate how the
      plasticity of a common protein fold can contribute to the recognition and control
      of antagonists by an innate defence mechanism, whereby the monovalency of the
      lectin for its ligand implies a novel mechanism of lectin-mediated toxicity.

PMID- 22615565
TI  - Immunogenetic mechanisms driving norovirus GII.4 antigenic variation.
AB  - Noroviruses are the principal cause of epidemic gastroenteritis worldwide with
      GII.4 strains accounting for 80% of infections. The major capsid protein of GII.4
      strains is evolving rapidly, resulting in new epidemic strains with altered
      antigenic potentials. To test if antigenic drift may contribute to GII.4
      persistence, human memory B cells were immortalized and the resulting human
      monoclonal antibodies (mAbs) characterized for reactivity to a panel of time
      ordered GII.4 virus-like particles (VLPs). Reflecting the complex exposure
      history of the volunteer, human anti-GII.4 mAbs grouped into three VLP reactivity
      patterns; ancestral (1987-1997), contemporary (2004-2009), and broad (1987-2009).
      NVB 114 reacted exclusively to the earliest GII.4 VLPs by EIA and blockade. NVB
      97 specifically bound and blocked only contemporary GII.4 VLPs, while NBV 111 and
      43.9 exclusively reacted with and blocked variants of the GII.4.2006 Minerva
      strain. Three mAbs had broad GII.4 reactivity. Two, NVB 37.10 and 61.3, also
      detected other genogroup II VLPs by EIA but did not block any VLP interactions
      with carbohydrate ligands. NVB 71.4 cross-neutralized the panel of time-ordered
      GII.4 VLPs, as measured by VLP-carbohydrate blockade assays. Using mutant VLPs
      designed to alter predicted antigenic epitopes, two evolving, GII.4-specific,
      blockade epitopes were mapped. Amino acids 294-298 and 368-372 were required for
      binding NVB 114, 111 and 43.9 mAbs. Amino acids 393-395 were essential for
      binding NVB 97, supporting earlier correlations between antibody blockade escape
      and carbohydrate binding variation. These data inform VLP vaccine design, provide
      a strategy for expanding the cross-blockade potential of chimeric VLP vaccines,
      and identify an antibody with broadly neutralizing therapeutic potential for the
      treatment of human disease. Moreover, these data support the hypothesis that
      GII.4 norovirus evolution is heavily influenced by antigenic variation of
      neutralizing epitopes and consequently, antibody-driven receptor switching; thus,
      protective herd immunity is a driving force in norovirus molecular evolution.

PMID- 22615567
TI  - Functional analysis of NopM, a novel E3 ubiquitin ligase (NEL) domain effector of
      Rhizobium sp. strain NGR234.
AB  - Type 3 effector proteins secreted via the bacterial type 3 secretion system
      (T3SS) are not only virulence factors of pathogenic bacteria, but also influence
      symbiotic interactions between nitrogen-fixing nodule bacteria (rhizobia) and
      leguminous host plants. In this study, we characterized NopM (nodulation outer
      protein M) of Rhizobium sp. strain NGR234, which shows sequence similarities with
      novel E3 ubiquitin ligase (NEL) domain effectors from the human pathogens
      Shigella flexneri and Salomonella enterica. NopM expressed in Escherichia coli,
      but not the non-functional mutant protein NopM-C338A, showed E3 ubiquitin ligase
      activity in vitro. In vivo, NopM, but not inactive NopM-C338A, promoted
      nodulation of the host plant Lablab purpureus by NGR234. When NopM was expressed
      in yeast, it inhibited mating pheromone signaling, a mitogen-activated protein
      (MAP) kinase pathway. When expressed in the plant Nicotiana benthamiana, NopM
      inhibited one part of the plant's defense response, as shown by a reduced
      production of reactive oxygen species (ROS) in response to the flagellin peptide
      flg22, whereas it stimulated another part, namely the induction of defense genes.
      In summary, our data indicate the potential for NopM as a functional NEL domain
      E3 ubiquitin ligase. Our findings that NopM dampened the flg22-induced ROS burst
      in N. benthamiana but promoted defense gene induction are consistent with the
      concept that pattern-triggered immunity is split in two separate signaling
      branches, one leading to ROS production and the other to defense gene induction.

PMID- 22615568
TI  - Induction of GADD34 is necessary for dsRNA-dependent interferon-beta production
      and participates in the control of Chikungunya virus infection.
AB  - Nucleic acid sensing by cells is a key feature of antiviral responses, which
      generally result in type-I Interferon production and tissue protection. However,
      detection of double-stranded RNAs in virus-infected cells promotes two
      concomitant and apparently conflicting events. The dsRNA-dependent protein kinase
      (PKR) phosphorylates translation initiation factor 2-alpha (eIF2alpha) and
      inhibits protein synthesis, whereas cytosolic DExD/H box RNA helicases induce
      expression of type I-IFN and other cytokines. We demonstrate that the phosphatase
      1 cofactor, growth arrest and DNA damage-inducible protein 34 (GADD34/Ppp1r15a),
      an important component of the unfolded protein response (UPR), is absolutely
      required for type I-IFN and IL-6 production by mouse embryonic fibroblasts (MEFs)
      in response to dsRNA. GADD34 expression in MEFs is dependent on PKR activation,
      linking cytosolic microbial sensing with the ATF4 branch of the UPR. The
      importance of this link for anti-viral immunity is underlined by the extreme
      susceptibility of GADD34-deficient fibroblasts and neonate mice to Chikungunya
      virus infection.

PMID- 22615569
TI  - CD200 receptor controls sex-specific TLR7 responses to viral infection.
AB  - Immunological checkpoints, such as the inhibitory CD200 receptor (CD200R), play a
      dual role in balancing the immune system during microbial infection. On the one
      hand these inhibitory signals prevent excessive immune mediated pathology but on
      the other hand they may impair clearance of the pathogen. We studied the
      influence of the inhibitory CD200-CD200R axis on clearance and pathology in two
      different virus infection models. We find that lack of CD200R signaling strongly
      enhances type I interferon (IFN) production and viral clearance and improves the
      outcome of mouse hepatitis corona virus (MHV) infection, particularly in female
      mice. MHV clearance is known to be dependent on Toll like receptor 7 (TLR7)
      mediated type I IFN production and sex differences in TLR7 responses previously
      have been reported for humans. We therefore hypothesize that CD200R ligation
      suppresses TLR7 responses and that release of this inhibition enlarges sex
      differences in TLR7 signaling. This hypothesis is supported by our findings that
      in vivo administration of synthetic TLR7 ligand leads to enhanced type I IFN
      production, particularly in female Cd200(-/-) mice and that CD200R ligation
      inhibits TLR7 signaling in vitro. In influenza A virus infection we show that
      viral clearance is determined by sex but not by CD200R signaling. However,
      absence of CD200R in influenza A virus infection results in enhanced lung
      neutrophil influx and pathology in females. Thus, CD200-CD200R and sex are host
      factors that together determine the outcome of viral infection. Our data predict
      a sex bias in both beneficial and pathological immune responses to virus
      infection upon therapeutic targeting of CD200-CD200R.

PMID- 22615570
TI  - Interferon-induced Ifit2/ISG54 protects mice from lethal VSV neuropathogenesis.
AB  - Interferon protects mice from vesicular stomatitis virus (VSV) infection and
      pathogenesis; however, it is not known which of the numerous interferon
      stimulated genes (ISG) mediate the antiviral effect. A prominent family of ISGs
      is the interferon-induced with tetratricopeptide repeats (Ifit) genes comprising
      three members in mice, Ifit1/ISG56, Ifit2/ISG54 and Ifit3/ISG49. Intranasal
      infection with a low dose of VSV is not lethal to wild-type mice and all three
      Ifit genes are induced in the central nervous system of the infected mice. We
      tested their potential contributions to the observed protection of wild-type mice
      from VSV pathogenesis, by taking advantage of the newly generated knockout mice
      lacking either Ifit2 or Ifit1. We observed that in Ifit2 knockout (Ifit2(-/-))
      mice, intranasal VSV infection was uniformly lethal and death was preceded by
      neurological signs, such as ataxia and hind limb paralysis. In contrast, wild
      type and Ifit1(-/-) mice were highly protected and survived without developing
      such disease. However, when VSV was injected intracranially, virus replication
      and survival were not significantly different between wild-type and Ifit2(-/-)
      mice. When administered intranasally, VSV entered the central nervous system
      through the olfactory bulbs, where it replicated equivalently in wild-type and
      Ifit2(-/-) mice and induced interferon-beta. However, as the infection spread to
      other regions of the brain, VSV titers rose several hundred folds higher in
      Ifit2(-/-) mice as compared to wild-type mice. This was not caused by a broadened
      cell tropism in the brains of Ifit2(-/-) mice, where VSV still replicated
      selectively in neurons. Surprisingly, this advantage for VSV replication in the
      brains of Ifit2(-/-) mice was not observed in other organs, such as lung and
      liver. Pathogenesis by another neurotropic RNA virus, encephalomyocarditis virus,
      was not enhanced in the brains of Ifit2(-/-) mice. Our study provides a clear
      demonstration of tissue-, virus- and ISG-specific antiviral action of interferon.

PMID- 22615571
TI  - Extracellular superoxide dismutase protects Histoplasma yeast cells from host
      derived oxidative stress.
AB  - In order to establish infections within the mammalian host, pathogens must
      protect themselves against toxic reactive oxygen species produced by phagocytes
      of the immune system. The fungal pathogen Histoplasma capsulatum infects both
      neutrophils and macrophages but the mechanisms enabling Histoplasma yeasts to
      survive in these phagocytes have not been fully elucidated. We show that
      Histoplasma yeasts produce a superoxide dismutase (Sod3) and direct it to the
      extracellular environment via N-terminal and C-terminal signals which promote its
      secretion and association with the yeast cell surface. This localization permits
      Sod3 to protect yeasts specifically from exogenous superoxide whereas
      amelioration of endogenous reactive oxygen depends on intracellular dismutases
      such as Sod1. While infection of resting macrophages by Histoplasma does not
      stimulate the phagocyte oxidative burst, interaction with polymorphonuclear
      leukocytes (PMNs) and cytokine-activated macrophages triggers production of
      reactive oxygen species (ROS). Histoplasma yeasts producing Sod3 survive co
      incubation with these phagocytes but yeasts lacking Sod3 are rapidly eliminated
      through oxidative killing similar to the effect of phagocytes on Candida albicans
      yeasts. The protection provided by Sod3 against host-derived ROS extends in vivo.
      Without Sod3, Histoplasma yeasts are attenuated in their ability to establish
      respiratory infections and are rapidly cleared with the onset of adaptive
      immunity. The virulence of Sod3-deficient yeasts is restored in murine hosts
      unable to produce superoxide due to loss of the NADPH-oxidase function. These
      results demonstrate that phagocyte-produced ROS contributes to the immune
      response to Histoplasma and that Sod3 facilitates Histoplasma pathogenesis by
      detoxifying host-derived reactive oxygen thereby enabling Histoplasma survival.

PMID- 22615572
TI  - Gammaherpesvirus latency accentuates EAE pathogenesis: relevance to Epstein-Barr
      virus and multiple sclerosis.
AB  - Epstein-Barr virus (EBV) has been identified as a putative environmental trigger
      of multiple sclerosis (MS), yet EBV's role in MS remains elusive. We utilized
      murine gamma herpesvirus 68 (gammaHV-68), the murine homolog to EBV, to examine
      how infection by a virus like EBV could enhance CNS autoimmunity. Mice latently
      infected with gammaHV-68 developed more severe EAE including heightened paralysis
      and mortality. Similar to MS, gammaHV-68EAE mice developed lesions composed of
      CD4 and CD8 T cells, macrophages and loss of myelin in the brain and spinal cord.
      Further, T cells from the CNS of gammaHV-68 EAE mice were primarily Th1,
      producing heightened levels of IFN-gamma and T-bet accompanied by IL-17
      suppression, whereas a Th17 response was observed in uninfected EAE mice.
      Clearly, gammaHV-68 latency polarizes the adaptive immune response, directs a
      heightened CNS pathology following EAE induction reminiscent of human MS and
      portrays a novel mechanism by which EBV likely influences MS and other autoimmune
      diseases.

PMID- 22615573
TI  - Identification and functional analysis of the S-layer protein SplA of
      Paenibacillus larvae, the causative agent of American Foulbrood of honey bees.
AB  - The gram-positive, spore-forming bacterium Paenibacillus larvae is the
      etiological agent of American Foulbrood (AFB), a globally occurring, deathly
      epizootic of honey bee brood. AFB outbreaks are predominantly caused by two
      genotypes of P. larvae, ERIC I and ERIC II, with P. larvae ERIC II being the more
      virulent genotype on larval level. Recently, comparative proteome analyses have
      revealed that P. larvae ERIC II but not ERIC I might harbour a functional S-layer
      protein, named SplA. We here determine the genomic sequence of splA in both
      genotypes and demonstrate by in vitro self-assembly studies of recombinant and
      purified SplA protein in combination with electron-microscopy that SplA is a true
      S-layer protein self-assembling into a square 2D lattice. The existence of a
      functional S-layer protein is novel for this bacterial species. For elucidating
      the biological function of P. larvae SplA, a genetic system for disruption of
      gene expression in this important honey bee pathogen was developed. Subsequent
      analyses of in vivo biological functions of SplA were based on comparing a wild
      type strain of P. larvae ERIC II with the newly constructed splA-knockout mutant
      of this strain. Differences in cell and colony morphology suggest that SplA is a
      shape-determining factor. Marked differences between P. larvae ERIC II wild-type
      and mutant cells with regard to (i) adhesion to primary pupal midgut cells and
      (ii) larval mortality as measured in exposure bioassays corroborate the
      assumption that the S-layer of P. larvae ERIC II is an important virulence
      factor. Since SplA is the first functionally proven virulence factor for this
      species, our data extend the knowledge of the molecular differences between these
      two genotypes of P. larvae and contribute to explaining the observed differences
      in virulence. These results present an immense advancement in our understanding
      of P. larvae pathogenesis.

PMID- 22615575
TI  - Rates of viral evolution are linked to host geography in bat rabies.
AB  - Rates of evolution span orders of magnitude among RNA viruses with important
      implications for viral transmission and emergence. Although the tempo of viral
      evolution is often ascribed to viral features such as mutation rates and
      transmission mode, these factors alone cannot explain variation among closely
      related viruses, where host biology might operate more strongly on viral
      evolution. Here, we analyzed sequence data from hundreds of rabies viruses
      collected from bats throughout the Americas to describe dramatic variation in the
      speed of rabies virus evolution when circulating in ecologically distinct
      reservoir species. Integration of ecological and genetic data through a
      comparative bayesian analysis revealed that viral evolutionary rates were labile
      following historical jumps between bat species and nearly four times faster in
      tropical and subtropical bats compared to temperate species. The association
      between geography and viral evolution could not be explained by host metabolism,
      phylogeny or variable selection pressures, and instead appeared to be a
      consequence of reduced seasonality in bat activity and virus transmission
      associated with climate. Our results demonstrate a key role for host ecology in
      shaping the tempo of evolution in multi-host viruses and highlight the power of
      comparative phylogenetic methods to identify the host and environmental features
      that influence transmission dynamics.

PMID- 22615574
TI  - Global analysis of the evolution and mechanism of echinocandin resistance in
      Candida glabrata.
AB  - The evolution of drug resistance has a profound impact on human health. Candida
      glabrata is a leading human fungal pathogen that can rapidly evolve resistance to
      echinocandins, which target cell wall biosynthesis and are front-line
      therapeutics for Candida infections. Here, we provide the first global analysis
      of mutations accompanying the evolution of fungal drug resistance in a human host
      utilizing a series of C. glabrata isolates that evolved echinocandin resistance
      in a patient treated with the echinocandin caspofungin for recurring bloodstream
      candidemia. Whole genome sequencing identified a mutation in the drug target,
      FKS2, accompanying a major resistance increase, and 8 additional non-synonymous
      mutations. The FKS2-T1987C mutation was sufficient for echinocandin resistance,
      and associated with a fitness cost that was mitigated with further evolution,
      observed in vitro and in a murine model of systemic candidemia. A CDC6
      A511G(K171E) mutation acquired before FKS2-T1987C(S663P), conferred a small
      resistance increase. Elevated dosage of CDC55, which acquired a C463T(P155S)
      mutation after FKS2-T1987C(S663P), ameliorated fitness. To discover strategies to
      abrogate echinocandin resistance, we focused on the molecular chaperone Hsp90 and
      downstream effector calcineurin. Genetic or pharmacological compromise of Hsp90
      or calcineurin function reduced basal tolerance and resistance. Hsp90 and
      calcineurin were required for caspofungin-dependent FKS2 induction, providing a
      mechanism governing echinocandin resistance. A mitochondrial respiration
      defective petite mutant in the series revealed that the petite phenotype does not
      confer echinocandin resistance, but renders strains refractory to synergy between
      echinocandins and Hsp90 or calcineurin inhibitors. The kidneys of mice infected
      with the petite mutant were sterile, while those infected with the HSP90
      repressible strain had reduced fungal burden. We provide the first global view of
      mutations accompanying the evolution of fungal drug resistance in a human host,
      implicate the premier compensatory mutation mitigating the cost of echinocandin
      resistance, and suggest a new mechanism of echinocandin resistance with broad
      therapeutic potential.

PMID- 22615576
TI  - Separation of DNA replication from the assembly of break-competent meiotic
      chromosomes.
AB  - The meiotic cell division reduces the chromosome number from diploid to haploid
      to form gametes for sexual reproduction. Although much progress has been made in
      understanding meiotic recombination and the two meiotic divisions, the processes
      leading up to recombination, including the prolonged pre-meiotic S phase (meiS)
      and the assembly of meiotic chromosome axes, remain poorly defined. We have used
      genome-wide approaches in Saccharomyces cerevisiae to measure the kinetics of pre
      meiotic DNA replication and to investigate the interdependencies between
      replication and axis formation. We found that replication initiation was delayed
      for a large number of origins in meiS compared to mitosis and that meiotic cells
      were far more sensitive to replication inhibition, most likely due to the
      starvation conditions required for meiotic induction. Moreover, replication
      initiation was delayed even in the absence of chromosome axes, indicating
      replication timing is independent of the process of axis assembly. Finally, we
      found that cells were able to install axis components and initiate recombination
      on unreplicated DNA. Thus, although pre-meiotic DNA replication and meiotic
      chromosome axis formation occur concurrently, they are not strictly coupled. The
      functional separation of these processes reveals a modular method of building
      meiotic chromosomes and predicts that any crosstalk between these modules must
      occur through superimposed regulatory mechanisms.

PMID- 22615577
TI  - Integrin alpha PAT-2/CDC-42 signaling is required for muscle-mediated clearance
      of apoptotic cells in Caenorhabditis elegans.
AB  - Clearance of apoptotic cells by engulfment plays an important role in the
      homeostasis and development of multicellular organisms. Despite the fact that the
      recognition of apoptotic cells by engulfment receptors is critical in inducing
      the engulfment process, the molecular mechanisms are still poorly understood.
      Here, we characterize a novel cell corpse engulfment pathway mediated by the
      integrin alpha subunit PAT-2 in Caenorhabditis elegans and show that it
      specifically functions in muscle-mediated engulfment during embryogenesis.
      Inactivation of pat-2 results in a defect in apoptotic cell internalization. The
      PAT-2 extracellular region binds to the surface of apoptotic cells in vivo, and
      the intracellular region may mediate signaling for engulfment. We identify
      essential roles of small GTPase CDC-42 and its activator UIG-1, a guanine
      nucleotide exchange factor, in PAT-2-mediated cell corpse removal. PAT-2 and CDC
      42 both function in muscle cells for apoptotic cell removal and are co-localized
      in growing muscle pseudopods around apoptotic cells. Our data suggest that PAT-2
      functions through UIG-1 for CDC-42 activation, which in turn leads to
      cytoskeletal rearrangement and apoptotic cell internalization by muscle cells.
      Moreover, in contrast to PAT-2, the other integrin alpha subunit INA-1 and the
      engulfment receptor CED-1, which signal through the conserved signaling molecules
      CED-5 (DOCK180)/CED-12 (ELMO) or CED-6 (GULP) respectively, preferentially act in
      epithelial cells to mediate cell corpse removal during mid-embryogenesis. Our
      results show that different engulfing cells utilize distinct repertoires of
      receptors for engulfment at the whole organism level.

PMID- 22615578
TI  - Genomic hypomethylation in the human germline associates with selective
      structural mutability in the human genome.
AB  - The hotspots of structural polymorphisms and structural mutability in the human
      genome remain to be explained mechanistically. We examine associations of
      structural mutability with germline DNA methylation and with non-allelic
      homologous recombination (NAHR) mediated by low-copy repeats (LCRs). Combined
      evidence from four human sperm methylome maps, human genome evolution, structural
      polymorphisms in the human population, and previous genomic and disease studies
      consistently points to a strong association of germline hypomethylation and
      genomic instability. Specifically, methylation deserts, the ~1% fraction of the
      human genome with the lowest methylation in the germline, show a tenfold
      enrichment for structural rearrangements that occurred in the human genome since
      the branching of chimpanzee and are highly enriched for fast-evolving loci that
      regulate tissue-specific gene expression. Analysis of copy number variants (CNVs)
      from 400 human samples identified using a custom-designed array comparative
      genomic hybridization (aCGH) chip, combined with publicly available structural
      variation data, indicates that association of structural mutability with germline
      hypomethylation is comparable in magnitude to the association of structural
      mutability with LCR-mediated NAHR. Moreover, rare CNVs occurring in the genomes
      of individuals diagnosed with schizophrenia, bipolar disorder, and developmental
      delay and de novo CNVs occurring in those diagnosed with autism are significantly
      more concentrated within hypomethylated regions. These findings suggest a new
      connection between the epigenome, selective mutability, evolution, and human
      disease.

PMID- 22615579
TI  - Inactivation of a novel FGF23 regulator, FAM20C, leads to hypophosphatemic
      rickets in mice.
AB  - Family with sequence similarity 20,-member C (FAM20C) is highly expressed in the
      mineralized tissues of mammals. Genetic studies showed that the loss-of-function
      mutations in FAM20C were associated with human lethal osteosclerotic bone
      dysplasia (Raine Syndrome), implying an inhibitory role of this molecule in bone
      formation. However, in vitro gain- and loss-of-function studies suggested that
      FAM20C promotes the differentiation and mineralization of mouse mesenchymal cells
      and odontoblasts. Recently, we generated Fam20c conditional knockout (cKO) mice
      in which Fam20c was globally inactivated (by crossbreeding with Sox2-Cre mice) or
      inactivated specifically in the mineralized tissues (by crossbreeding with 3.6 kb
      Col 1a1-Cre mice). Fam20c transgenic mice were also generated and crossbred with
      Fam20c cKO mice to introduce the transgene in the knockout background. In vitro
      gain- and loss-of-function were examined by adding recombinant FAM20C to MC3T3-E1
      cells and by lentiviral shRNA-mediated knockdown of FAM20C in human and mouse
      osteogenic cell lines. Surprisingly, both the global and mineralized tissue
      specific cKO mice developed hypophosphatemic rickets (but not osteosclerosis),
      along with a significant downregulation of osteoblast differentiation markers and
      a dramatic elevation of fibroblast growth factor 23 (FGF23) in the serum and
      bone. The mice expressing the Fam20c transgene in the wild-type background showed
      no abnormalities, while the expression of the Fam20c transgene fully rescued the
      skeletal defects in the cKO mice. Recombinant FAM20C promoted the differentiation
      and mineralization of MC3T3-E1 cells. Knockdown of FAM20C led to a remarkable
      downregulation of DMP1, along with a significant upregulation of FGF23 in both
      human and mouse osteogenic cell lines. These results indicate that FAM20C is a
      bone formation "promoter" but not an "inhibitor" in mouse osteogenesis. We
      conclude that FAM20C may regulate osteogenesis through its direct role in
      facilitating osteoblast differentiation and its systemic regulation of phosphate
      homeostasis via the mediation of FGF23.

PMID- 22615580
TI  - Slowing replication in preparation for reduction.

PMID- 22615581
TI  - Psip1/Ledgf p52 binds methylated histone H3K36 and splicing factors and
      contributes to the regulation of alternative splicing.
AB  - Increasing evidence suggests that chromatin modifications have important roles in
      modulating constitutive or alternative splicing. Here we demonstrate that the
      PWWP domain of the chromatin-associated protein Psip1/Ledgf can specifically
      recognize tri-methylated H3K36 and that, like this histone modification, the
      Psip1 short (p52) isoform is enriched at active genes. We show that the p52, but
      not the long (p75), isoform of Psip1 co-localizes and interacts with Srsf1 and
      other proteins involved in mRNA processing. The level of H3K36me3 associated
      Srsf1 is reduced in Psip1 mutant cells and alternative splicing of specific genes
      is affected. Moreover, we show altered Srsf1 distribution around the
      alternatively spliced exons of these genes in Psip1 null cells. We propose that
      Psip1/p52, through its binding to both chromatin and splicing factors, might act
      to modulate splicing.

PMID- 22615582
TI  - Karyotypic determinants of chromosome instability in aneuploid budding yeast.
AB  - Recent studies in cancer cells and budding yeast demonstrated that aneuploidy,
      the state of having abnormal chromosome numbers, correlates with elevated
      chromosome instability (CIN), i.e. the propensity of gaining and losing
      chromosomes at a high frequency. Here we have investigated ploidy- and chromosome
      specific determinants underlying aneuploidy-induced CIN by observing karyotype
      dynamics in fully isogenic aneuploid yeast strains with ploidies between 1N and
      2N obtained through a random meiotic process. The aneuploid strains exhibited
      various levels of whole-chromosome instability (i.e. chromosome gains and
      losses). CIN correlates with cellular ploidy in an unexpected way: cells with a
      chromosomal content close to the haploid state are significantly more stable than
      cells displaying an apparent ploidy between 1.5 and 2N. We propose that the
      capacity for accurate chromosome segregation by the mitotic system does not scale
      continuously with an increasing number of chromosomes, but may occur via discrete
      steps each time a full set of chromosomes is added to the genome. On top of such
      general ploidy-related effect, CIN is also associated with the presence of
      specific aneuploid chromosomes as well as dosage imbalance between specific
      chromosome pairs. Our findings potentially help reconcile the divide between gene
      centric versus genome-centric theories in cancer evolution.

PMID- 22615583
TI  - Drosophila activated Cdc42 kinase has an anti-apoptotic function.
AB  - Activated Cdc42 kinases (Acks) are evolutionarily conserved non-receptor tyrosine
      kinases. Activating somatic mutations and increased ACK1 protein levels have been
      found in many types of human cancers and correlate with a poor prognosis. ACK1 is
      activated by epidermal growth factor (EGF) receptor signaling and functions to
      regulate EGF receptor turnover. ACK1 has additionally been found to propagate
      downstream signals through the phosphorylation of cancer relevant substrates.
      Using Drosophila as a model organism, we have determined that Drosophila Ack
      possesses potent anti-apoptotic activity that is dependent on Ack kinase activity
      and is further activated by EGF receptor/Ras signaling. Ack anti-apoptotic
      signaling does not function through enhancement of EGF stimulated MAP kinase
      signaling, suggesting that it must function through phosphorylation of some
      unknown effector. We isolated several putative Drosophila Ack interacting
      proteins, many being orthologs of previously identified human ACK1 interacting
      proteins. Two of these interacting proteins, Drk and yorkie, were found to
      influence Ack signaling. Drk is the Drosophila homolog of GRB2, which is required
      to couple ACK1 binding to receptor tyrosine kinases. Drk knockdown blocks Ack
      survival activity, suggesting that Ack localization is important for its pro
      survival activity. Yorkie is a transcriptional co-activator that is downstream of
      the Salvador-Hippo-Warts pathway and promotes transcription of proliferative and
      anti-apoptotic genes. We find that yorkie and Ack synergistically interact to
      produce tissue overgrowth and that yorkie loss of function interferes with Ack
      anti-apoptotic signaling. Our results demonstrate how increased Ack signaling
      could contribute to cancer when coupled to proliferative signals.

PMID- 22615584
TI  - Deletion of PTH rescues skeletal abnormalities and high osteopontin levels in
      Klotho-/- mice.
AB  - Maintenance of normal mineral ion homeostasis is crucial for many biological
      activities, including proper mineralization of the skeleton. Parathyroid hormone
      (PTH), Klotho, and FGF23 have been shown to act as key regulators of serum
      calcium and phosphate homeostasis through a complex feedback mechanism. The
      phenotypes of Fgf23(-/-) and Klotho(-/-) (Kl(-/-)) mice are very similar and
      include hypercalcemia, hyperphosphatemia, hypervitaminosis D, suppressed PTH
      levels, and severe osteomalacia/osteoidosis. We recently reported that complete
      ablation of PTH from Fgf23(-/-) mice ameliorated the phenotype in Fgf23(-/-)/PTH(
      /-) mice by suppressing serum vitamin D and calcium levels. The severe
      osteomalacia in Fgf23(-/-) mice, however, persisted, suggesting that a different
      mechanism is responsible for this mineralization defect. In the current study, we
      demonstrate that deletion of PTH from Kl(-/-) (Kl(-/-)/PTH(-/-) or DKO) mice
      corrects the abnormal skeletal phenotype. Bone turnover markers are restored to
      wild-type levels; and, more importantly, the skeletal mineralization defect is
      completely rescued in Kl(-/-)/PTH(-/-) mice. Interestingly, the correction of the
      osteomalacia is accompanied by a reduction in the high levels of osteopontin
      (Opn) in bone and serum. Such a reduction in Opn levels could not be observed in
      Fgf23(-/-)/PTH(-/-) mice, and these mice showed sustained osteomalacia. This
      significant in vivo finding is corroborated by in vitro studies using calvarial
      osteoblast cultures that show normalized Opn expression and rescued
      mineralization in Kl(-/-)/PTH(-/-) mice. Moreover, continuous PTH infusion of Kl(
      /-) mice significantly increased Opn levels and osteoid volume, and decreased
      trabecular bone volume. In summary, our results demonstrate for the first time
      that PTH directly impacts the mineralization disorders and skeletal deformities
      of Kl(-/-), but not of Fgf23(-/-) mice, possibly by regulating Opn expression.
      These are significant new perceptions into the role of PTH in skeletal and
      disease processes and suggest FGF23-independent interactions of PTH with Klotho.

PMID- 22615586
TI  - Investigation of formulation variables affecting the properties of lamotrigine
      nanosuspension using fractional factorial design.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Lamotrigine (LMG) undergoes extensive
      hepatic metabolism upon oral administration and its absorption is affected in the
      presence of food. This study was aimed to develop nanosuspension of LMG and
      investigate its formulation characteristics using L(9) orthogonal array. METHODS:
      Nanosuspension was prepared using emulsification-solvent diffusion method. All
      the formulations were subjected to in-vitro evaluation and the statistically
      optimized one was used for stability, scanning electron microscopic and
      differential scanning calorimetric studies. RESULTS: Nanoparticles were spherical
      with little surface adsorbed drug. Formulation characteristics in terms of size,
      zeta potential, polydispersity index (PDI), entrapment efficiency (EE), drug
      content and in vitro drug release were consistent and within their acceptable
      range. All the batches provided a burst release profile during first 1 hr,
      followed by a controlled release extending up to 24 hrs. The values of n in
      Peppas model ranged between 0.2-0.4 for all the formulations indicative of
      Fickian release mechanism. The formulation remained reasonably stable up to 3
      months. No interaction was observed among the drug and polymers. MAJOR
      CONCLUSION: Results of in vitro drug release studies suggested that
      nanosuspension might be used as a sustained delivery vehicle for LMG. Statistical
      analysis revealed that size of the nanoparticles was most strongly affected by
      stabilizer type while EE was influenced by the drug-to-polymer ratio.

PMID- 22615585
TI  - Target gene analysis by microarrays and chromatin immunoprecipitation identifies
      HEY proteins as highly redundant bHLH repressors.
AB  - HEY bHLH transcription factors have been shown to regulate multiple key steps in
      cardiovascular development. They can be induced by activated NOTCH receptors, but
      other upstream stimuli mediated by TGFbeta and BMP receptors may elicit a similar
      response. While the basic and helix-loop-helix domains exhibit strong similarity,
      large parts of the proteins are still unique and may serve divergent functions.
      The striking overlap of cardiac defects in HEY2 and combined HEY1/HEYL knockout
      mice suggested that all three HEY genes fulfill overlapping function in target
      cells. We therefore sought to identify target genes for HEY proteins by
      microarray expression and ChIPseq analyses in HEK293 cells, cardiomyocytes, and
      murine hearts. HEY proteins were found to modulate expression of their target
      gene to a rather limited extent, but with striking functional interchangeability
      between HEY factors. Chromatin immunoprecipitation revealed a much greater number
      of potential binding sites that again largely overlap between HEY factors.
      Binding sites are clustered in the proximal promoter region especially of
      transcriptional regulators or developmental control genes. Multiple lines of
      evidence suggest that HEY proteins primarily act as direct transcriptional
      repressors, while gene activation seems to be due to secondary or indirect
      effects. Mutagenesis of putative DNA binding residues supports the notion of
      direct DNA binding. While class B E-box sequences (CACGYG) clearly represent
      preferred target sequences, there must be additional and more loosely defined
      modes of DNA binding since many of the target promoters that are efficiently
      bound by HEY proteins do not contain an E-box motif. These data clearly establish
      the three HEY bHLH factors as highly redundant transcriptional repressors in
      vitro and in vivo, which explains the combinatorial action observed in different
      tissues with overlapping expression.

PMID- 22615587
TI  - Development of matrix type transdermal patches of lercanidipine hydrochloride:
      physicochemical and in-vitro characterization.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Lercanidipine hydrochloride (LRDP) is
      used in the treatment of hypertension because of its selectivity and specificity
      on the smooth vascular cells. The pharmacokinetic parameters make LRDP a suitable
      candidate for transdermal delivery. The purpose of the study was to select a
      suitable formulation for the development of transdermal drug-delivery system
      (TDDS) of LRDP and to determine the effect of penetration enhancer, limonene on
      drug permeation METHODS: The matrix type TDDS of LRDP were prepared by solvent
      evaporation technique. Formulations A1, A2, A3, A4, A5 and A6 were composed of
      Eudragit RL100 (ERL) and hydroxypropyl methyl cellulose (HPMC) in 1.5:8.5, 3:7,
      4:6, 6:4, 7:3 and 8.5:1.5 ratios respectively. All the six formulations carried
      10 mg of LRDP/patch area, 8% v/w of d-limonene as a penetration enhancer, 20% v/w
      of propylene glycol as plasticizer in methanol and dichloromethane as solvent
      system. The prepared TDDS were evaluated for physicochemical characteristics, in
      vitro release, ex-vivo permeation and skin irritation. The ex-vivo permeation
      studies were carried out across excised rat skin using Franz diffusion cell.
      RESULTS: All the formulations exhibited satisfactory physicochemical
      characteristics. Cumulative percentage of the drug released in 24 hrs from the
      six formulations were 82.0%, 74.9%, 63.2%, 63.5%, 59.8% and 53.5% respectively.
      Corresponding values for the cumulative amounts of the drug permeated across the
      rat skin for the above matrix films were 2644.5, 2347.2, 2249.5, 1933.4, 2021.5
      and 1663.4 ug/cm(2) respectively. By fitting the data into zero order, first
      order and Higuchi model, it was concluded that drug release from matrix films
      followed Higuchi model and the mechanism of the drug release was diffusion
      mediated. The patches were seemingly free of potentially hazardous skin
      irritation. CONCLUSIONS: The patches composed of ERL, HPMC (1.5:8.5) with 8% v/w
      limonene as penetration enhancer may be selected for the development of TDDS of
      LRDP for potential therapeutic use by using a suitable adhesive layer and backing
      membrane.

PMID- 22615588
TI  - Molecular analysis of MEN1 expression in MCF7, T47D and MDA-MB 468 breast cancer
      cell lines treated with adriamycin using RT-PCR and immunocytochemistry.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: MEN1 is an important tumor suppressor
      gene that encodes a nuclear protein called menin. Recent data suggest that
      interactions between menin and other proteins have important roles in control of
      the cell cycle and apoptosis. In addition, estrogen receptor (ER), an important
      prognostic factor is differentially expressed in breast cancer cells. In this
      study the MEN1 gene and protein expression in MCF7, T47D and MDA-MB-468 breast
      cancer cell lines with different ER status following exposure to adriamycin (ADR)
      was investigated. MATERIALS AND METHODS: Cytotoxicity of ADR on these cell lines
      was determined using MTT assay. The mRNA and protein levels were analyzed in
      tested cell lines using RT-PCR and immunocytochemistry (ICC) assays,
      respectively. RESULTS: ADR cytotoxicity was highest on MDA-MB-468 and lowest on
      MCF7 cells. MEN1 mRNA showed significant decrease after ADR exposure only in the
      MDA-MB-468 cell line. Menin protein expression was higher in MDA-MB-468 and lower
      in MCF7 cells. CONCLUSION: Differential molecular responses to adriamycin were
      observed in cancer cell lines. Molecular data also suggest that MEN1 as a new
      biomarker can be used in combination with current biomarkers for prediction of
      response to chemotherapy.

PMID- 22615589
TI  - Examination of Setarud (IMODTM) in the management of patients with severe sepsis.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Analysis of current immunomodulating
      strategies indicates that monovalent approaches are unlikely to restore
      immunostasis or achieve complete therapy of sepsis. Setarud (IMOD) as a mixture
      of urtica, carotenoids, urea, and selenium has been recently patented for its
      potential in reduction of Tumor Necrosis Factor alpha (TNF-alpha) and Interferon
      gamma and Interleukin-2 levels. The aim of this study was to examine efficacy of
      IMOD in the management of patients with severe sepsis. METHODS: Twenty patients
      with severe sepsis and acute physiology and chronic health evaluation (APACHE)
      score of more than 20 were randomized to receive standard treatment of severe
      sepsis (control group) or standard treatment plus IMOD (IMOD group). The group
      treated with IMOD for 14 days was according to the pilot study and regarding the
      stability of patient's conditions in the ICU. Of course patients in both groups
      received standard treatment and all were monitored for 28 days. Blood samples
      were analyzed for interleukins (IL-1, IL-2, IL-6), plasminogen activator
      inhibitor (PAI-1), TNF-alpha, total thiol molecules (TTM), nitric oxide (NO),
      total antioxidant power (TAP), and lipid peroxidation (LPO). Daily APACHE,
      Sequential Organ Failure Assessment (SOFA), and Simplified Acute Physiology Score
      (SAPS) were calculated. RESULTS AND MAJOR CONCLUSION: Comparing with controls,
      IMOD was significantly effective in improving SAPS, SOFA, and APACHE scores, and
      reduction of mortality rate. Among tested inflammatory biomarkers, IMOD
      significantly improved TTM and TNF-alpha values. It is concluded that IMOD might
      be added as a safe adjutant to standard treatment of severe sepsis.

PMID- 22615590
TI  - Formalin pain increases the concentration of serotonin and its 5
      hydroxyindoleacetic acid metabolite in the CA1 region of hippocampus.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: The hippocampal formation is involved in
      nociception. Prenatal serotonin depletion results in a significant decrease in
      the concentration of nociceptive sensitivity during the second phase of
      behavioral response in the formalin test. METHODS: A microdialysis probe was
      inserted via a guide cannula into the right CA1 region of the hippocampus.
      Extracellular serotonin (5HT) and its 5- hydroxyindoleacetic acid (5HIAA)
      metabolite overflow were collected every 10 min during the formalin test and
      measured by HPLC with electrochemichal detector. RESULTS: Compared to the sham
      group, formalin injection in the hind paw of the rat significantly increased 5HT
      after 10, 30, 40, and 50 min and increased 5HIAA after 10, 30, 40, 50, and 60 min
      collection time periods in hippocampal dialysate. (n=6 for each group at each
      sampling time). In the formalin treated rats serotonin and 5HIAA concentrations
      increased in the biphasic pattern in concert with the first and second phases of
      formalin pain. CONCLUSION: The hippocampal formation might be involved in the
      processing of nociceptive information and serotonin-related mechanisms in the
      hippocampus may play a role in the biphasic behavioral responses to formalin
      noxious stimulation.

PMID- 22615591
TI  - Inhibition of central angiotensin-converting enzyme with enalapril protects the
      brain from ischemia/reperfusion injury in normotensive rat.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Central Angiotensin Converting Enzyme
      (ACE) has an important role on cerebral microcirculation and metabolism. However,
      its role in terms of protecting the brain from ischemic/reperfusion (I/R) injury
      are debatable. This study evaluated the role of ACE, using enalapril as ACE
      inhibitor, in protection of the brain from I/R injury during transient focal
      cerebral ischemia (TFCI) in normotensive rat. METHOD: Male Sprague Dawley rats
      (280-320g) randomly assigned to control ischemic and enalapril pre-treated
      ischemic groups. Enalapril was injected intraperitoneally 1 h before middle
      cerebral artery occlusion (MCAO) at the dose of 0.03 or 0.1 mg/kg. Cerebral
      ischemia was induced by 60 min MCAO followed by 24 hrs reperfusion. After
      evaluation of neurological deficit scores (NDS) the animal was sacrificed for
      assessment of cerebral infarction and edema. RESULTS: TFCI induced cerebral
      infarctions (283+/-18 mm(3)), brain edema (4.1+/-0.4%) and swelling (9.8+/-1.5%)
      with NDS of 3.11+/-0.36. Non-hypotensive dose of enalapril (0.03 mg/kg) improved
      NDS (1.37+/-0.26), reduced cerebral infarction (45%), brain edema (54%) and
      swelling of the lesioned hemispheres (34%) significantly. However, hypotensive
      dose of enalapril (0.1 mg/kg) could improve neurological activity (1.67+/-0.31)
      and failed to reduce cerebral infarction (276+/-39 mm(3)) and swelling (10.4+/
      1.4%). CONCLUSION: In the rat model of transient focal cerebral ischemia,
      inhibition of angiotensin converting enzyme with non-hypotensive doses of
      enalapril has the benefit of improving neurological activity, reducing cerebral
      infarction, brain swelling and edema of acute ischemic stroke. Therefore, it is
      reasonable to conclude that central renin-angiotensin system may participate in
      ischemic/reperfusion injury of the cerebral cortex.

PMID- 22615593
TI  - Efficacy of topical phenytoin on chemotherapy-induced oral mucositis; a pilot
      study.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Oral mucositis is one of the most common
      complications of malignancy chemotherapy. As yet, no absolute treatment has been
      demonstrated to be effective for chemotherapy-induced oral mucositis. This study
      evaluates the effectiveness of phenytoin mouthwash as a wound healing agent, on
      the basis of stimulating effects on fibroblast proliferation. MATERIALS AND
      METHODS: In this multicenter, randomized, placebo-controlled clinical trial;
      twelve patients received phenytoin mouthwash (0.5%) or placebo for about two
      weeks. Oral pain severity was scored on the daily basis using a VAS (visual
      analogue scale) of 10 centimeters. National Cancer Institute (NCI) scale was used
      to grade the intensity of mucositis. To determine the effect of treatment, a
      quality of life questionnaire, consisting of 35 queries, was filled out for all
      patients. Statistical analyses of data was performed using Mann-Whitney test.
      RESULTS: The average time for complete remission of mucositis in phenytoin
      treated group was less than that of the placebo group. The quality of life
      improved dramatically in the phenytoin group with the healing process being more
      evident in the first week. Furthermore, reduction in the wound area was greater
      in the phenytoin group than controls at the end of the first week of treatment.
      Both groups eventually demonstrated reduction in pain intensity; however no
      statistically significant difference was observed between two groups. CONCLUSION:
      Phenytoin mouthwash accelerated wound healing and resolution of mucositis and
      improved life quality impressively.

PMID- 22615592
TI  - Buspirone improves haloperidol-induced Parkinson disease in mice through 5-HT(1A)
      recaptors.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: The available literatures show that 5
      HT(1A) receptors are widely distributed throughout the basal ganglia, and their
      activation facilitate dopamine release. Neuroleptic drugs such as haloperidol
      induce Parkinson-like syndrome through blocking brain D(2) receptors. This study
      aimed to investigate effect of buspirone, a partial agonist of 5HT(1A) receptor,
      on motor dysfunctions induced by haloperidol and involvement of 5HT(1A) receptors
      in this regard. METHODS: Study was performed on the male mice weighing 25-30 g.
      Animals were divided randomly to groups of 10 animals. Motor dysfunction was
      induced by intraperitoneal (i.p.) injection of haloperidol (1 mg/kg). Catalepsy
      was assayed by bar-test method 5, 60, 120 and 180 minutes after drug
      administration and motor imbalance was studied by rotarod test. RESULTS AND MAJOR
      CONCLUSION: Results showed that buspirone (20 mg/kg, i.p.) decreased
      significantly haloperidol-induced catalepsy and balance disorder in a dose
      dependent manner. Furthermore, 8-OH-DPAT (10 mg/kg, i.p.), as an agonist of 5
      HT(1A) receptor, decreased haloperidol-induced catalepsy and balance disorder.
      The effect of buspirone (20 mg/kg, i.p.) on haloperidol-induced motor disorders
      was abolished by NAN-190 (10 mg/kg, i.p.), as a 5-HT(1A) receptor antagonist.
      From the results it may be concluded that buspirone improves haloperidol-induced
      catalepsy and balance disorder through activation of 5-HT(1A) receptors.

PMID- 22615595
TI  - Selection for autochthonous bifidobacteial isolates adapted to simulated
      gastrointestinal fluid.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Bifidobacterial strains are excessively
      sensitive to acidic conditions and this can affect their living ability in the
      stomach and fermented foods, and as a result, restrict their use as live
      probiotic cultures. The aim of the present study was to obtain bifidobacterial
      isolates with augmented tolerance to simulated gastrointestinal condition using
      cross-protection method. METHODS: Individual bifidobacterial strains were treated
      in acidic environment and also in media containing bile salts and NaCl. Viability
      of the acid and acid-bile-NaCl tolerant isolates was further examined in
      simulated gastric and small intestine by subsequent incubation of the probiotic
      bacteria in the corresponding media for 120 min. Antipathogenic activities of the
      adapted isolates were compared with those of the original strains. RESULTS AND
      MAJOR CONCLUSION: The acid and acid-bile-NaCl adapted isolates showed improved
      viabilities significantly (p<0.05) in simulated gastric fluid compared to their
      parent strains. The levels of reduction in bacterial count (Log cfu/ml) of the
      acid and acid-bile-NaCl adapted isolates obtained in simulated gastric fluid
      ranged from 0.64-3.06 and 0.36-2.43 logarithmic units after 120 min of
      incubation. There was no significant difference between the viability of the acid
      bile-NaCl-tolerant isolates and the original strains in simulated small
      intestinal condition except for Bifidobacterium adolescentis (p<0.05). The
      presence of 15 ml of supernatants of acid-bile-NaCl-adapted isolates and also
      those of the initial Bifidobacterium strains inhibited pathogenic bacterial
      growth for 24 hrs. Probiotic bacteria with improved ability to survive in harsh
      gastrointestinal environment could be obtained by subsequent treatment of the
      strains in acid, bile salts and NaCl environments.

PMID- 22615594
TI  - Effects of aminoguanidine on infertile varicocelized rats: A functional and
      morphological study.
AB  - BACKGROUNDS AND THE PURPOSE OF THE STUDY: Inducible NO synthase activity has been
      frequently reported in varicose veins. Aminoguanidine is known to inhibit iNOS.
      The aim of this study was to examine the effects of aminoguanidine on
      varicocelized rats. METHODS: Male Wistar rats were divided into groups A, B, C,
      D, E, and F (control group). Groups A, B, C, and D rats underwent left varicocele
      induction with a 20-gauge needle. Group E (sham) rats underwent a similar
      procedure, but the renal vein was left intact. Ten weeks after varicocele
      induction, sperm parameters were evaluated in groups D, E, and F. Groups A and B
      received 50 mg/kg aminoguanidine or placebo, respectively, daily for 10 weeks.
      After 10 and 20 weeks of varicocele induction, the fertility outcomes of the
      experimental groups were evaluated. RESULTS: The values of the sperm parameters
      did not differ significantly between groups B and D, but were significant when
      compared with groups F and E (P<=0.05). The values of the sperm parameters of
      groups F and E showed no significant changes (P<=0.05). The changes between group
      A and groups B and D were significant (P<=0.05). Ten weeks after varicocele
      induction, rats of groups A, B, and C were still fertile. After 20 weeks, only
      half of the rats in group A were fertile. CONCLUSIONS: Aminoguanidine improved
      the sperm parameters and mating outcomes in vari-cocelized rats.

PMID- 22615597
TI  - Isolation of a new quinic acid derivative and its antibacterial modulating
      activity.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: The species Hymenocrater calycinus,
      belongs to the plant family Lamiaceae and grows wildly in the north-east of Iran.
      Previously, the antimicrobial activity of the plant extracts was reported. In the
      present study, the bioactivity-guided fractionation of the methanol extract of H.
      calycinus and the combination effects of the isolated compound with cell wall
      active agents against S. aureus and E. coli was investigated. METHODS: Column and
      thin layer chromatographic methods were used for isolation and purification and
      spectroscopic data (MS, (1)H- and (13)C-NMR, HMQC, HMBC and (1)H-(1)H COSY) were
      employed for identification of the compound isolated from the extract. A disk
      diffusion method was used to determine the antibacterial activity of the isolated
      compound against S. aureus and E. coli in comparison with 7 different
      antibiotics. RESULTS: The isolated compound 1 was identified as 3-(3, 4-
      dihydroxyphenyl) lactic acid 2-O-quinic acid. Compound 1 (500 ug/disc) enhanced
      antibacterial effect of ampicillin, ciprofloxacin, vancomycin and cefepime
      against S. aureus and activated the effects of ampicillin and vancomycin against
      E. coli. CONCLUSION: Results showed that the compound 1 was not active against
      both tested strains at any concentration below 1 mg/disk, and as a result the
      enhancing effect of the compound could be due its association with antibiotics.

PMID- 22615596
TI  - An efficient procedure for purification of recombinant human beta heat shock
      protein 90.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Heat Shock Protein 90 (Hsp90) is
      typically the most abundant chaperone in the eukaryotic cell cytoplasm, and its
      expression is essential for loading immunogenic peptides onto major
      histocompatibility complex molecules for presentation to T-cells. Therefore, it
      may act as a good candidate as an adjuvant molecule in vaccine technology.
      METHODS: Initially the human Hsp90beta gene was cloned into the heat inducible
      expression vector pGP1-2 and then the recombinant protein was isolated by ion
      exchange chromatography. After intradermal injection of confirmed purified band
      of protein to rabbits and isolation of the serum IgG antibody, for its affinity
      purification, the rabbit's purified Hsp90 specific IgG was coupled to the
      cyanogen bromide-activated Sepharose 4B. RESULTS: The recovery of the purified
      protein of interest by affinity chromatography was 50%. CONCLUSION: This research
      enabled purification of human heat shock protein by a laboratory prepared column
      chromatography.

PMID- 22615598
TI  - Physico-mechanical and dissolution behaviours of ibuprofen crystals crystallized
      in the presence of various additives.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: The success of any direct-tableting
      procedure is strongly affected by the quality of the crystals used in the
      process. Ibuprofen is a poorly compactible drug with a high tendency for capping.
      In order to use ibuprofen in direct compression formulations, physico-mechanical
      properties of ibuprofen should be improved considerably. The aim of the present
      investigation was to employ crystallization techniques in order to improve the
      physico- mechanical properties of ibuprofen for direct compression. METHODS: The
      experimental methods involved the preparation of ibuprofen crystals by solvent
      change technique. Ibuprofen was dissolved in ethanol and crystallized out with
      water in the absence or presence of various hydrophilic additives (PEG 6000,
      8000, Brij 98P and polyvinyl alcohol 22000, PVA (22000)) with different
      concentrations. The physico-mechanical properties of the ibuprofen crystals were
      studied in terms of flow, density, tensile strength and dissolution behaviour.
      Morphology of ibuprofen crystals was studied by scanning electron microscopic
      (SEM). Solid state of the recrystallized particles was also investigated using
      differential scanning calorimeter (DSC) and FT-IR. RESULTS: Ibuprofen samples
      crystallized in the presence of PEG 6000 and 8000 and PVA showed remarkable
      increase in the tensile strengths of the directly compressed tablets, while some
      other additives, i.e. Brij 98P did not produce improved ibuprofen crystals.
      Ibuprofen powders made from particles obtained in the presence of PVA and Brij
      98P showed similar dissolution profiles to the commercial ibuprofen particles.
      DSC and FT-IR results ruled out any significant interaction between ibuprofen and
      additives except for the samples crystallized in the presence of PEG 8000.
      CONCLUSION: The crystal habit of ibuprofen can be altered successfully by the
      crystallization technique which was developed in this study. The crystals
      developed in the presence of certain additives can be recommended for direct
      compression.

PMID- 22615599
TI  - Itraconazole nanosuspension for oral delivery: Formulation, characterization and
      in vitro comparison with marketed formulation.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Itraconazole is a poorly water soluble
      drug which results in its insufficient bioavailability. The purpose of the
      present study was to formulate Itraconazole in a nanosuspension to increase the
      aqueous solubility and to improve its formulation related parameters, dissolution
      and hence oral bioavailability. METHODS: Itraconazole nanosuspension was prepared
      by pearl milling technique using zirconium oxide beads as a milling media,
      Poloxamer 407 as a stabilizer and glycerol as a wetting agent. Effects of various
      process parameters like, stirring time and the ratio of the beads were optimized
      by keeping drug:surfactant:milling media (1:3.0:50) as a constant initially and
      then optimized process parameters were used to optimize formulation parameters by
      32 factorial designs. The optimized nanosuspension was lyophilized using mannitol
      (1:1 ratio) as a cryoprotectant. Nanosuspension was characterized by particle
      size and size distribution, drug content, scanning electron microscopy,
      differential scanning colorimetry and X-ray diffraction techniques. RESULTS:
      Optimized nanosuspension showed spherical shape with surface oriented surfactant
      molecules and a mean particle diameter of 294 nm. There was no significant change
      in crystalline nature after formulation and it was found to be chemically stable
      with high drug content. CONCLUSION: The in vitro dissolution profile of the
      optimized formulation compared to the pure drug and marketed formulation
      (Canditral Capsule) by using 0.1N Hydrochloric acid as release medium showed
      higher drug release.

PMID- 22615600
TI  - The effect of pectin on swelling and permeability characteristics of free films
      containing Eudragit RL and/or RS as a coating formulation aimed for colonic drug
      delivery.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: The potential of pectin as a bacterially
      degradable polysaccharide for colon drug delivery has been demonstrated. Due to
      the high solubility and swelling properties of pectin in aqueous media, it is
      frequently used in combination with water insoluble polymers for targeting drugs
      to the colon. The aim of this study was to evaluate free films containing pectin
      as a bacterially-degradable polysaccharide in combination with Eudragit RL (ERL)
      and/or RS (ERS) as a coating formulation for colonic drug delivery. METHODS:
      Isolated free films comprising 20% pectin and 80% ERL or ERS and their
      combination in 1:1 ratio were prepared by casting method. Then, free films were
      evaluated by water vapor transmission (WVT), swelling and permeability
      experiments for theophylline and indomethacin in different media. RESULTS:
      Formulations containing ERL exhibited higher WVT, swelling and permeability
      compared with formulations containing ERS. The permeability of theophylline
      through free films composed of pectin and eudragit polymers in simulated colonic
      media was not significantly different from those obtained in other media. However
      indomethacin free films containing pectin and ERL showed higher permeation in
      simulated colonic fluid (SCF) compared to the other media. MAJOR CONCLUSION:
      Formulation containing pectin and ERL may be suitable as a coating formulation
      for colon targeted delivery of drugs of low solubility such as indomethacin.

PMID- 22615601
TI  - Development and validation of a rapid HPLC- fluorescence method for simultaneous
      determination of venlafaxine and its major metabolites in human plasma.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: To develop a simple, rapid and accurate
      HPLC method for the measurement of the venlafaxine and its main metabolites, O
      desmethylvenlafaxine and O,N-didesmethylvenlafaxine in pharmacokinetic studies
      and therapeutic drug monitoring. METHOD: Chromatographic separation was achieved
      with a ChromolithTM Performance RP-18e 100 mm*4.6 mm column equipped with a
      Fluorescence detectore (lambda(ex) 200 nm/lambda(em) 300 nm) The mobile phase of
      methanol:water (35:65, v/v) adjusted to pH 2.5 by phosphoric acid was passed
      through the column in an isocratic mode at flow rate of 2 ml/min. The sample
      preparation involved a simple, one-step, extraction with ethyl acetate. RESULTS:
      The calibration curves were linear in the concentration range of 1-300 ng/ml for
      all analytes (r2>0.998). The lower limit of quantification was 1 ng/ml for all
      analytes. Within and between day precisions in the measurement of quality control
      (QC) of samples were in the range of 1.8-14.1% for all analytes. CONCLUSION: The
      developed procedure was used to assess the pharmacokinetics of venlafaxine and
      its main metabolites following oral administration of 75 mg venlafaxine to a
      healthy subject.

PMID- 22615602
TI  - Comparison the inflammatory effects of early supplemental parenteral nutrition
      plus enteral nutrition versus enteral nutrition alone in critically ill patients.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: It is believed that enteral nutrition
      (EN) support is the preferred route as compared to parenteral nutrition (PN).
      Critically ill patients on EN receive less than 60% of their metabolic
      requirements. To meet patients' calorie goal addition of PN to EN was proposed.
      This study was conducted to determine whether supplemental PN have any difference
      with EN alone in regard to inflammatory indices. METHODS: Twenty patients were
      randomized to either receive EN alone or EN+PN for 7 days. Pre albumin and
      inflammatory indices including interleukin IL-1, IL-6 and tumor necrosis factor
      alpha (TNF-alpha) were measured on days of 0, 3,7. Also Sequential Organ Failure
      Assessment (SOFA) score and Therapeutic Intervention Scoring System-28 (TISS-28)
      score were calculated on days of 0, 3 and 7. RESULTS AND MAJOR CONCLUSION: IL-1,
      IL-6 and TNF-alpha did not show significant difference between two interventions.
      Pre-albumin was increased from baseline by 9% and 81% in EN and EN+PN groups
      respectively but it did not reach to statistical significance. SOFA score did not
      show significant difference. TISS score was higher in EN+PN group on days of 3
      and 7. No difference was found between EN and EN+PN regimens in regard to
      inflammation, while severity of illness may not change with these regimens,
      nursing workload increases with implementation of supplemental PN.

PMID- 22615604
TI  - Evaluation of the plasma quality after filtration.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: The quality of some of the human plasma
      derived drugs such as coagulation factor VIII and coagulation factor IX which can
      be used for the treatment of hemophilia A and B, depends on their activity which
      may be affected by filtration. In this study the quality of plasma with respect
      to coagulation factors FVII, FVIII, FIX, FV, FXI, Fibrinogen, antithrombin III,
      anti-plasmin and antitrypsin activities obtained after plasma filtration with CPD
      (citrate-phosphate-dextrose) using integral filter was evaluated. METHODS: Sixty
      units of plasma were individually separated from whole blood by centrifugation
      and immediately filtered by integral filter system. Specific plasma filtration
      was carried out between 4 and 20 hrs after blood donation. Before filtration, 60
      units of non filtered fresh plasmas were kept as control. Coagulation factors
      were determined by one-stage clotting assay in an automated system. Antithrombin
      III activity was determined by immunochrom assay in an automated system. Activity
      of anti-plasmin was determined by Berichrom alpha(2)-antiplasmin and antitrypsin
      activity was assayed with human neutrophil elastase. RESULTS: The activity of
      coagulation factors FVIII, FIX, Fibrinogen, FV, and FXI, were not affected by
      filtration, in all experiments. Filtration only caused negligible change in FVII
      activity. Antithrombin III, anti-plasmin and antitrypsin activities were not
      influenced by filtration. Nonfiltrated and filtrated plasma values were not
      significantly different (P> 0.05). CONCLUSIONS: Plasma filtration dose not result
      in a measurable impairment of coagulation factors and inhibitors. Although a
      little changes in FVII activity was observed after filtration, but these
      filtration-dependent changes apparently have no impact on the therapeutic quality
      of whole blood- filtered fresh plasma for transfusion.

PMID- 22615603
TI  - Impact of anti-cancer drugs and other determinants on serum protein binding of
      morphine 6-glucuronide.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: The aim of the present study was to
      examine factors that may influence the protein binding of morphine 6-glucuronide
      (M6G), the most active metabolite of morphine. METHODS: An enzyme-linked
      immunoabsorbent assay technique was used to measure the M6G concentration in
      serum of 18 healthy adults, 18 neonatal and 7 children with cancer. Total and
      free M6G concentrations were measured following equilibrium dialysis for 3 hrs
      and at physiological pH at 37 degrees C. The influence of vincristine,
      methotrexate, 6-mercaptopurine, morphine, human albumin, alpha-1-acid
      glycoprotein, palmitic acid, oleic acid and pH on M6G protein binding was
      examined. RESULTS: M6G was 66.87+/-0.73 percent free in human serum at
      physiological pH and temperature. The percentage free (unbound) was increased
      significantly by vincristine (4.33%) and methotrexate (9.68%), but 6-
      mercaptopurine and morphine had no significant effect on it. Free percentages of
      M6G was reduced by decreasing serum albumin concentration but was unaffected by
      the presence of alpa-1-acid glycoprotein (AAG) or changes in serum pH. Similar
      results were obtained in human serum albumin (HAS) solutions. Addition of
      palmitic acid and oleic acid reduced protein binding significantly by 6.3% and
      7.4%, respectively. MAJOR CONCLUSION: Although M6G in this study was not highly
      bounded, but because of its high analgesic potency, any change in its free
      concentration due to concurrent medication or disease caused significant changes
      in its effects. This dearth of evidence has been implicated in the reluctance of
      professionals to be cautious in prescribing them to children, particularly in the
      neonatal period.

PMID- 22615605
TI  - Synthesis and cloxacillin antimicrobial enhancement of 2-methylsulfonylimidazolyl
      1,4-dihydropyridine derivatives.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Hospital-acquired methicillin-resistant
      Staphylococcus aureus (MRSA) has been a major problem worldwide in chemotherapy
      of infection disease. This study was designed to assess the enhancing effects of
      a new group of dihydropyridine-3,5dicarboxamides, in combination with cloxacillin
      with distinctly different mechanisms of action against MRSAs. MATERIAL AND
      METHODS: Dihydropyridine-3,5-dicarboxamides with 2-methylsulfonylimidazole at 4
      position 6a-k were synthesized by the reaction of corresponding aldehyde 5 with
      different N-aryl acetoacetamides 3 in the presence of ammonium hydroxide. Agar
      disc diffusion method was used to determine the antibacterial and potentiating
      activity of different synthetic compounds in the presence and absence of
      cloxacillin to evaluate their activity as modulators of multidrugresistant (MDR).
      RESULTS AND MAJOR CONCLUSION: The antibacterial effect of cloxacillin was
      enhanced by compounds 6g and 6h against cloxacillin-resistant strains (MRSA(1)
      and MRSA(2)). The potentiation was found 1 2 to be statistically significant
      (p<0.01). Compound 6g at concentration of 1000 ug/disc, caused a 329 percent
      potentiation of the activity of cloxacillin against MRSA(1).

PMID- 22615606
TI  - The first phytochemical report of Galanthus transcaucasicus Fomin.
AB  - BACKGROUND AND THE PURPOSE OF STUDY: Galanthus transcaucasicus Fomin
      (Amaryllidaceae) is an endemic species to the Caucasia and Alborz mountains in
      Iran which locally named "Gole-Barfi". While there are many reports on
      pharmacological activities of Galanthus species' alkaloids, there is no report on
      G. transcaucasicus and this article is the first phytochemical study on this
      species. METHODS: Extracted alkaloids from G. transcaucasicus bulbs were isolated
      using different chromatographic methods and the structures of the components were
      determined by physical and spectroscopic data. RESULTS: Five isoquinoline type
      alkaloids namely galanthamine (8.04%), narwedine (6.90%), lycorine (19.48%),
      caranine (3.45%) and tazettine (5.75%) of total alkaloid extract were isolated
      from the bulbs of Galanthus transcaucasicus Fomin. MAJOR CONCLUSION: Because of
      the presence of biologically active alkaloids especially galanthamine and the
      major alkaloid lycorine in Gol-e-Barfi, the plant may be used as a natural source
      for pharmaceutical purposes.

PMID- 22615607
TI  - An investigation of the neuroprotective effects of Curcumin in a model of
      Homocysteine - induced oxidative stress in the rat's brain.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Aging is the major risk factor for
      neurodegenerative diseases and oxidative stress is involved in the
      pathophysiology of them. Oxidative stress can induce neuronal damages and
      modulate intracellular signaling, ultimately leading to neuronal death by
      apoptosis or necrosis. In this study, the possible antioxidant and
      neuroprotective properties of the natural polyphenolic antioxidant compound,
      curcumin against homocysteine (Hcy) neurotoxicity was investigated. METHODS:
      Curcumin (5, 15, 45 mg/kg) was injected intraperitonealy (i.p.) once daily for a
      period of 10 days beginning 5 days prior to Hcy (0.2 umol/ul)
      intracerebroventricular (i.c.v) injection in rats. Biochemical and behavioral
      studies, including passive avoidance learning and locomotor activity tests were
      studied 24 hrs after the last curcumin or its vehicle injection. The cell density
      of hippocampus layers and apoptosis in rats' hippocampi by immunohistochical
      methods were also studied. RESULTS AND MAJOR CONCLUSION: Results indicated that
      Hcy could induce lipid peroxidation and increase Malondialdehyde (MDA) and Super
      Oxide Anion (SOA) levels in rat's brain. Additionally, Hcy impaired memory
      retention in passive avoidance learning test. However, curcumin decreased MDA and
      SOA levels significantly and improved learning and memory in rats. On the other
      hand Hcy could induce cell death and apoptosis in rats' hippocampi which was
      inhibited by curcumin. These results suggest that Hcy may induce lipid
      peroxidation in rat's brain. and polyphenol treatment (curcumin) improves
      learning and memory deficits by protecting the nervous system against Oxidative
      stress.

PMID- 22615608
TI  - Role of NADPH-insensitive nitroreductase gene to metronidazole resistance of
      Helicobacter pylori strains.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Current anti-H. pylori therapies are
      based on the use of two antibiotics with a proton pump inhibitor and/or a bismuth
      component. Metronidazole is a key component of such combination therapies in
      Iran. The aim of this study was to determine the role of rdxA gene in resistant
      strains of H. pylori isolated from Shahrekord Hajar hospital to metronidazole.
      METHODS: This study was a cross-sectional method, which was carried out on 263
      patients who referred to endoscopy department of Hajar hospital, in 2007. Biopsy
      samples were cultured on selective Brucella agar containing 10% blood and
      incubated under microerophilic condition at 370C for 3-7 days. Suspected colonies
      were tested by Gram staining, urease, oxidase and catalase activities. Organisms
      were confirmed to be H. pylori on the basis of the presence of ureC(glmM) gene by
      PCR.Specific primers were used for detection of rdxA gene mutation. RESULTS:
      Eighty and four strains of H. pylori determined by PCR method. Of the isolated
      strains, 49 (58.33%) were resistant, 7 (8.33%) were semi-sensitive to
      metronidazole and 200bp deletion in rdxA gene was observed in 2 strains.
      CONCLUSION: Because of the high metronidazole resistance in patients under study
      it was necessary to replace it by other antibiotics in therapeutic regimens. On
      the basis of low frequency of resistance mutation in rdxA gene, sequence analysis
      for identification of other mechanisms is suggested.

PMID- 22615609
TI  - Primary WWOX phosphorylation and JNK activation during etoposide induces
      cytotoxicity in HEK293 cells.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Etoposide is an antineoplastic agent
      used in multiple cancers. It is known that etoposide induce cell death via
      interaction with topoisomerase II; however, the etopoisde cellular response is
      poorly understood. Upon etoposide induced DNA damage, many stress signaling
      pathways including JNK are activated. In response to DNA damage, it has been
      shown that WWOX, a recently introduced tumor suppressor, can be activated. In
      this study the activation of WWOX and JNK and their interaction following
      etoposide treatment were evaluated. MATERIALS AND METHODS: HEK293 cells treated
      with etoposide were lysed in a time course manner. The whole cell lysates were
      used to evaluate JNK and WWOX activation pattern using Phospho specific
      antibodies on western blots. The viability of cells treated with etoposide, JNK
      specific inhibitor and their combination was examined using MTT assay. RESULTS:
      Findings of this study indicate that WWOX and JNK are activated in a simultaneous
      way in response to DNA damage. Moreover, JNK inhibition enhances etoposide
      induced cytotoxicity in HEK293. CONCLUSION: Taken together, our results indicate
      that etoposide induces cytotoxicity and WWOX phosphorylation and the cytotoxicty
      is augmented by blocking JNK pathway.

PMID- 22615610
TI  - Pharmacological management of metabolic syndrome and its lipid complications.
AB  - Obesity epidemic has been spread all over the world in the past few decades and
      has caused a major public health concern due to its increasing global prevalence.
      Obese individuals are at higher risks of developing dyslipidemic characteristics
      resulting in increased triglyceride and LDL-cholesterol content and reduced HDL
      cholesterol levels. This disorder has profound implications as afflicted
      individuals have been demonstrated to be at increased risk of development of
      hypertension, atherosclerosis, type 2 diabetes and cardiovascular diseases.
      Today, this phenotype is designated as metabolic syndrome. According to the
      criteria set by the International Diabetes Federation (IDF), for a patient to be
      diagnosed with metabolic syndrome, the person must have central obesity plus any
      two of the following conditions: raised TG, reduced HDL-cholesterol, raised blood
      pressure, and increased fasting plasma glucose. Current National Cholesterol
      Education Program Adult Treatment Panel III (NCEP-ATP III) guidelines for the
      treatment of patients with the metabolic syndrome encourage therapies that lower
      LDL cholesterol and TG and raise HDL-cholesterol. Primary intervention often
      involves treatment with statins to improve the lipid profiles of these patients.
      However, recent studies suggest the potential of newly identified drugs including
      thiazolidinediones, GLP-1 agonists, and DPP-4 inhibitors that seem to be
      promising in reducing the level of progression of metabolic syndrome related
      disorders. This review discusses the current pharmacological treatments of the
      metabolic syndrome with the above mentioned drugs.

PMID- 22615611
TI  - Identification of enhanced cytokine generation following sepsis. Dream of magic
      bullet for mortality prediction and therapeutic evaluation.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: sepsis is one of the most widespread and
      lethal disease in Intensive Care Units (ICU). Based on pathophisyology of sepsis,
      it seems that routine laboratory tests combined with analysis of pro-inflammatory
      cytokines plasma levels, help clinicians to have more information about disease
      progress and its correct management. METHODS: This was a prospective
      observational study to determine the predictive role of Tumor Necrosis Factor
      alpha (TNF-alpha), Interleukin (IL)-1beta and IL-6 as three main pro-inflammatory
      cytokines and Acute Physiology and Chronic Health Evaluation (APACHE II) and
      Sequential Organ Failure Assessment (SOFA) as two scoring systems in mortality of
      critically ill patients with severe sepsis. Fifty and five patients with criteria
      of severe sepsis were included in this study. An exclusion criterion was post
      Cardiopulmonary Resuscitation (CPR) status. Cytokines (TNF-alpha, IL-1beta and IL
      6) were assayed in the first, third and seventh days in blood of patients.
      RESULTS AND MAJOR CONCLUSION: Among three measured cytokines, sequential levels
      of TNF-alpha and IL-6 showed significant differences between survivors and
      nonsurvivors. IL-6 had a good correlation with outcome and scoring systems during
      the period of this study. The areas under the receiver operating characteristic
      (AUROC) curve indicated that APACHE II (0.858, 0.848, 0.861) and IL-6 (0.797,
      0.799, 0.899) had discriminative power in prediction of mortality during
      sequental measured days. Multiple logestic regression analysis identified that
      evaluation of APACHE II and TNF-alpha in the first day and APACHE II and IL-6 in
      the third and seventh days of severe septic patients are independent outcome
      predictors. Results of this study suggest that IL-6 and APACHE II are useful
      cytokine and scoring systems respectively in prediction of mortality and clinical
      evaluation of severe septic patients.

PMID- 22615612
TI  - The effect of full length and mature NAG-1 protein overexpression on cytotoxicity
      of celecoxib, tamoxifen and doxorubicin in HT1080.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Non-steroidal anti-inflammatory drug
      activated gene-1 (NAG-1) is involved in inflammation, apoptosis/survival and
      tumorigenesis as well as resistance to chemotherapy. NAG-1 protein is synthesized
      as pro-peptide, cleaved and secreted as mature protein. Regulation of NAG-1 is
      not completely discovered and increased level of NAG-1 has been reported in many
      cancers. The expression of NAG-1 in cancer cells could affect the progression of
      tumor growth. In addition the secretion of full length and mature forms of NAG-1
      can influence cell proliferation in other cells. In this study the role of full
      length and mature forms of NAG-1 on viability of HT-1080 and MCF-7 cells were
      evaluated, and the cytotoxicity of celecoxib, indomethacin, tamoxifen and
      doxorubicin in HT1080 cells stably expressing NAG-1 were also tested. METHODS:
      Full length and mature NAG-1 was cloned from cDNA library of HCT116 cells and
      stably transfected in HT1080 cells. Cells were treated with different
      concentrations of indomethacin, celecoxib, tamoxifen and doxorubicin and
      viability was assessed by MTT assay. The effect of conditioned medium of NAG-1
      expressing cells on proliferation of MCF-7 and HT1080 cells were also tested.
      RESULTS: The growth curves of HT1080 cells expressing full length and mature NAG
      1 were not different. The viability of HT1080 cells expressing NAG-1 in the
      presence of indomethacin, doxorubicin and tamoxifen compared to untransfected
      cells was higher. The proliferation of HT1080 and MCF-7 cells were inhibited by
      conditioned medium of NAG-1 expressing cells in 24 and 48 hrs. MAJOR CONCLUSION:
      NAG-1 expression enhances drug resistance to tamoxifen, indomethacin and
      doxorubicin in HT1080. In addition, condition medium of NAG-1 expression cells
      inhibits proliferation in MCF-7 and HT1080 cells. Thus, NAG-1 expression can
      induce drug resistance in NAG-1 expressing cells and inhibition of viability in
      non expressing cells. Thus, NAG-1 is suggested as a marker for effective cancer
      chemotherapy and tumor progression.

PMID- 22615613
TI  - Synthesis and antimicrobial effects of silver nanoparticles produced by chemical
      reduction method.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: The most prominent nanoparticles for
      medical uses are nanosilver particles which are famous for their high anti
      microbial activity. Silver ion has been known as a metal ion that exhibit anti
      mold, anti-microbial and anti-algal properties for a long time. In particular, it
      is widely used as silver nitrate aqueous solution which has disinfecting and
      sterilizing actions. The purpose of this study was to evaluate the antimicrobial
      activity as well as physical properties of the silver nanoparticles prepared by
      chemical reduction method. METHODS: Silver nanoparticles (NPs) were prepared by
      reduction of silver nitrate in the presence of a reducing agent and also poly [N
      vinylpyrolidone] (PVP) as a stabilizer. Two kinds of NPs were synthesized by
      ethylene glycol (EG) and glucose as reducing agent. The nanostructure and
      particle size of silver NPs were confirmed by scanning electron microscopy (SEM)
      and laser particle analyzer (LPA). The formations of the silver NPs were
      monitored using ultraviolet- visible spectroscopy. The anti-bacterial activity of
      silver NPs were assessed by determination of their minimum inhibitory
      concentrations (MIC) against the Gram positive (Staphylococcus aureus and
      Staphylococcus epidermidis) as well as Gram-negative (Escherichia coli and
      Pseudomonas aeruginosa) bacteria. RESULTS AND CONCLUSION: The silver
      nanoparticles were spherical with particle size between 10 to 250 nm. Analysis of
      the theoretical (Mie light scattering theory) and experimental results showed
      that the silver NPs in colloidal solution had a diameter of approximately 50 nm.
      Both colloidal silver NPs showed high anti-bacterial activity against Gram
      positive and Gram negative bacteria. Glucose nanosilver colloids showed a shorter
      killing time against most of the tested bacteria which could be due to their
      nanostructures and uniform size distribution patterns.

PMID- 22615614
TI  - Measurement of melatonin in alcoholic and hot water extracts of Tanacetum
      parthenium, Tripleurospermum disciforme and Viola odorata.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Melatonin has recently been found in
      several plant tissues. Some reports show that the majority of the herbs
      containing the high level of melatonin have been used traditionally to treat
      neurological disorders or diseases associated with the generation of free
      radicals. Current study was undertaken to screen some medicinal plant species
      with historical evidence of efficacy in the treatment of neurological and
      antioxidant deficiency related disorders for their melatonin content. The
      melatonin content of boiled and alcoholic extracts were also compared. METHODS:
      In this study, three medicinal herbs, Tanacetum parthenium (L.) Schultz. Bip.
      (Asteraceae), Tripleurospermum disciforme (C.A.Mey) Schultz. Bip. (Asteraceae)
      and Viola odorata (L.) (Violaceae) were analyzed using high performance liquid
      chromatography with ultraviolet detector (HPLC-UV), enzyme linked immunosorbent
      assay (ELISA) and thin layer chromatography (TLC). RESULTS: Melatonin content in
      the dry plant powders differed with different assay methods (p < 0.001). For
      example, the melatonin content in T. disciforme was determined as 3.073 ug/g and
      2.906 ug/g by the HPLC and the ELISA methods, respectively. MAJOR CONCLUSION: The
      results demonstrated that a hydroalcoholic solution could extract more melatonin
      from flowers of the herbs than hot water (p < 0.001). The presence of melatonin
      in these plant tissues may provide some explanation for the anecdotal evidence of
      their physiological effects in humans.

PMID- 22615615
TI  - Spectroscopic studies on the interaction between erlotinib hydrochloride and
      bovine serum albumin.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: The binding ability of a drug to serum
      albumin has influence on the pharmacokinetics of a drug. In the present study,
      the mutual interaction of anticancer drug erlotinib hydrochloride with bovine
      serum albumin (BSA) using fluorescence and UV/vis spectroscopy was investigated.
      METHODS: The BSA solution (0.1 mM) was prepared daily in Tris buffer (0.05 mol l
      1, pH =7.4) and treated at final concentration of 1.67*10-5 M with different
      amounts of erlotinib hydrochloride to obtain final concentrations of 0, 0.2, 0.4,
      0.8, 1, 2, 4, 6, 8, 20 and 42 uM receptively. The mixture was allowed to stand
      for 5 min and the fluorescence quenching spectra were recorded at 298, 303, 308
      and 313 K. RESULTS: It was found that erlotinib hydrochloride caused the
      fluorescence quenching of BSA by the formation of a BSA-erlotinib hydrochloride
      complex. The mechanism of the complex formation was then analyzed by
      determination of the number of binding sites, apparent binding constant K, and
      calculation of the corresponding thermodynamic parameters such as the free energy
      (?G), enthalpy (?H) and entropy changes (?S) at different temperatures. Results
      showed that binding of erlotinib hydrochloride to BSA was spontaneous, and the
      hydrophobic forces played a major role in the complex formation. The distance, r,
      between donor (BSA) and acceptor (erlotinib hydrochloride) was found to be less
      than 8 nm suggesting the occurrence of non-radiative energy transferring and
      static quenching between these two molecules. CONCLUSION: The results provided
      preliminary information on the binding of erlotinib hydrochloride to BSA and the
      presence of a single binding site on BSA and K values for the association of BSA
      with erlotinib hydrochloride increased by the increase in temperature.

PMID- 22615616
TI  - Preparation and in-vitro evaluation of indomethacin nanoparticles.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: During the last two decades one of the
      most important problems in drug formulations has been low aqueous solubility of
      new molecules. However, numerous techniques, such as milling, co-solvent
      solubilization and solid dispersion have been used conventionally for aqueous
      solubility enhancement and the rate of solubility. Recently, nanoparticle
      engineering processes have been developed and reported for pharmaceutical
      applications to increase the dissolution rate of low-soluble drugs which in turn
      may leads to substantial increases in bioavailability. In this study, a
      controlled precipitation method was used to produce indomethacin nano-solid
      suspension in a polymeric matrix (as a model), in order to increase the
      solubility and rate of the dissolution of poorly soluble model drug. METHODS:
      Nano-solid suspension of indomethacin in polyvinyl pyrrolidine (PVP) was prepared
      by controlled precipitation technique, characterized by differential scanning
      calorimetry (DSC), X-ray diffraction (XRD), Fourier Transform Infrared
      Spectroscopy (FTIR) and evaluated for in vitro solubility and dissolution rate.
      RESULTS AND MAJOR CONCLUSION: Absence of thermal and diffractional peaks in DSC
      and XRD studies indicated that indomethacin interacts with PVP in solid phase.
      The solubility of indomethacin in nano-solid suspension compared to crystalline
      form was increased to about four-fold. It was found that particle size
      distribution depend to the polymer MW and drug: polymer ratios. Spectroscopy
      methods and Transmission Electron Microscopy (TEM) images showed that
      indomethacin dispersed as amorphous nanosize particles in freeze dried powder.
      Enhanced solubility and dissolution rate of indomethacin compared to physical
      mixtures and crystalline form of indomethacin (polymorph I), demonstrated that it
      interacts with PVP via hydrogen bond and probably forming eutectic mixture.

PMID- 22615617
TI  - Comparative in vitro and in vivo evaluation of three tablet formulations of
      amiodarone in healthy subjects.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: The relative in vivo bioavailability and
      in vitro dissolution studies of three chemically equivalent amiodarone generic
      products in healthy volunteers was evaluated in three separate occasions. The
      possibility of a correlation between in vitro and in vivo performances of these
      tablet formulations was also evaluated. METHODS: The bioequivalence studies were
      conducted based on a single dose, two-sequence, cross over randomized design. The
      bioavailability was compared using AUC(0-72), AUC(0-8), C(max) and T(max).
      Similarity factor, dissolution efficiency (DE), and mean dissolution time (MDT)
      was used to compare the dissolution profiles. Polynomial linear correlation
      models were tested using either MDT vs mean residence time (MRT) or fraction of
      the drug dissolved (FRD) vs fraction of the drug absorbed (FRA). RESULTS:
      Significant differences were found in the dissolution performances of the tested
      formulations and therefore they were included in the development of the
      correlation. The 90% confidence intervals of the log-transformed AUC0-72, AUC(0
      8), and C(max) of each two formulations in each bioequivalence studies were
      within the acceptable range of 80-125%. Differences were not observed between the
      untransformed T(max) values. Poor correlation was found between MRT and MDT of
      the products. A point-to-point correlation which is essential for a reliable
      correlation was not obtained between pooled FRD and FRA. The dissolution
      condition which was used for amiodarone tablets failed for formulations which
      were bioequivalent in vivo and significant difference between the dissolution
      characteristics of products (f2<50) did not reflect their in vivo properties.
      MAJOR CONCLUSIONS: Bioequivalence studies should be considered as the only
      acceptable way to ensure the interchangeability and in vivo equivalence of
      amiodarone generic drug products. The dissolution conditions used of the present
      study could be used for routine and in-process quality control of amiodarone
      tablet formulations.

PMID- 22615618
TI  - Preparation and characterization of superporous hydrogels as gastroretentive drug
      delivery system for rosiglitazone maleate.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Many drugs which have narrow therapeutic
      window and are absorbed mainly in stomach have been developed as gastroretentive
      delivery system. Rosiglitazone maleate, an anti-diabetic, is highly unstable at
      basic pH and is extensively absorbed from the stomach. Hence there is a need to
      develop a gastroretentive system. In this study a superporous hydrogel was
      developed as a gastroretentive drug delivery system. METHODS: Chitosan/poly(vinyl
      alcohol) interpenetrating polymer network type superporous hydrogels were
      prepared using a gas foaming method employing glyoxal as the crosslinking agent
      for Rosiglitazone maleate. Sodium bicarbonate was applied as a foaming agent to
      introduce the porous structure. Swelling behaviors of superporous hydrogel in
      acidic solution were studied to investigate their applications for gastric
      retention device. The optimum preparation condition of superporous hydrogels was
      obtained from the gelation kinetics. FT-IR, scanning electron microscopy,
      porosity and swelling ratio studies were used to characterize these polymers. In
      vitro drug release studies were also carried out. RESULTS: The introduction of a
      small amount of Poly(Vinyl Alcohol) enhanced the mechanical strength but slightly
      reduced the swelling ratio. The prepared superporous hydrogels were highly
      sensitive to pH of swelling media, and showed reversible swelling and de-swelling
      behaviors maintaining their mechanical stability. The degradation kinetics in
      simulated gastric fluid showed that it had biodegradability. Swelling was
      dependent on the amount of chitosan and crosslinker. The drug release from
      superporous hydrogels was sustained for 6 hrs. MAJOR CONCLUSION: The studies
      showed that chitosan-based superporous hydrogels could be used as a
      gastroretentive drug delivery system for rosiglitazone maleate in view of their
      swelling and prolonged drug release characteristics in acidic pH.

PMID- 22615619
TI  - Evaluation of potential of Zn-pectinate gel (ZPG) microparticles containing
      mesalazine for colonic drug delivery.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Pectin derivatives have been utilized
      for colonic drug delivery (CDD). In this study the effects of different
      formulation variables upon the characteristics of pectinate microparticles (MPs)
      prepared by ionotropic gelation technique for colonic delivery of mesalazine was
      investigated. METHODS: In-vitro drug release of MPs was studied using USP XXIV
      dissolution apparatus type I, in different fluids e.g. simulated gastric fluid
      (SGF: pH 1.2), simulated intestinal fluid (SIF: pH 7.4), and simulated colonic
      fluid (SCF: pH 6.8) of volume 900 ml, at 100 rpm maintained at 37+/-0.2 degrees
      C. This study was also performed in the presence of 4% w/v rat caecal content
      (RCC) using phosphate buffer saline (pH 6.8) as SCF. Gamma scintigraphy study was
      performed on New Zealand rabbit animal model using (99m) Tc. RESULTS: The results
      showed that maximum entrapment of mesalazine (86.1+/-1.7%) and strength of gel
      network zinc pectinate gel microparticles (ZPGD2) was achieved in cross-linking
      solution of pH 1.6. Batch of ZPGD2 showed least swelling ratio and drug release.
      In RCC medium the t(50%) value of CPG-MPs was 3-4 folds greater than ZPG-MPs.
      Scintigram showed the residence of ZPG-MPs (filled in enteric coated capsule) in
      colon more than 9 hrs and delivery of almost all the drug loading dose in colon.
      MAJOR CONCLUSION: The results of this study suggest the designed formulation of
      ZPG-MPs has the potential to serve as a colonic drug delivery system.

PMID- 22615620
TI  - Development of domperidone bilayered matrix type transdermal patches:
      physicochemical, in vitro and ex vivo characterization.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Domperidone (DOM) is a dopamine-
      receptor (D(2)) antagonist, which is widely used in the treatment of motion
      sickness. The pharmacokinetic parameters make DOM a suitable candidate for
      transdermal delivery. The purpose of the present investigation was to develop
      transdermal delivery systems for DOM and to evaluate their physicochemical
      characteristics, in vitro release an ex vivo permeation through rat abdominal
      skin and their mechanical properties. METHODS: Bilayered matrix type transdermal
      drug delivery systems (TDDS) of DOM were prepared by film casting technique using
      hydroxypropyl methyl cellulose as primary and Eudragit RL 100 as secondary
      layers. Brij-35 was incorporated as a solubilizer, d-limonene and propylene
      glycol were employed as permeation enhancer and plasticizer respectively. The
      prepared TDDS were extensively evaluated for in vitro release, moisture
      absorption, moisture content, water vapor transmission, ex vivo permeation
      through rat abdominal skin, mechanical properties and stability studies. The
      physicochemical interaction between DOM and polymers were investigated by
      Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared
      Spectroscopy (FTIR). RESULTS: All the formulations exhibited satisfactory
      physicochemical and mechanical characteristics. The optimized formulation F6
      showed maximum cumulative percentage of drug release (90.7%), permeation (6806.64
      ug) in 24 hrs, flux (86.02 ug /hr/cm(2)) and permeation coefficient of 0.86x10(
      2) cm/hr. Values of tensile strength (4.34 kg/mm(2)) and elastic modulus (5.89
      kg/cm(2)) revealed that formulation F6 was strong but not brittle. DSC and FTIR
      studies showed no evidence of interaction between the drug and polymers. A shelf
      life of 2 years is predicted for the TDDS. CONCLUSIONS: Domperidone bilayered
      matrix type transdermal therapeutic systems could be prepared with the required
      flux and suitable mechanical properties.

PMID- 22615621
TI  - Exploring the influence of steric, electronic and lipophilic descriptors of 1,3
      diarly propenones on their anti-inflammatory activity.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Various compounds from natural and
      synthetic origins containing the 1,3-diarylpropenone structure have been reported
      to produce a variety of biological activities like anti-microbial, anti
      inflammatory, vascular muscle relaxant, etc. A systematic analysis of the
      structural features responsible for anti-inflammatory activity and a possible
      mode of their actions were proposed to be evaluated by synthesizing a set of
      compounds, screening them for anti-inflammatory activity and developing a QSAR
      model. METHODS: Two types of 1,3-diarylpropenone derivatives were synthesized
      employing the Claisen-Schmidt condensation. These compounds were then screened
      for their in vivo anti- inflammatory activity by the carrageenin induced rat paw
      edema method and also for in vitro cyclooxygenase-2 (COX-2) inhibition activity
      using a colorimetric kit for COX (ovine) inhibitor screening assay. These
      derivatives and their anti-inflammatory activity data were employed for QSAR
      analysis on Vlife MDS 3.5 software. The molecules were divided into training and
      test sets based on observed activity and QSAR models were generated for the
      training set and validated. The activity of the molecules of the test set was
      predicted according to the QSAR equation fit. Possible correlation between
      observed anti-inflammatory activity and in vitro cyclooxygenase-2 inhibition was
      also studied. RESULTS AND CONCLUSION: Insignificant difference between the
      observed and predicted biological activity revealed that the selected electronic,
      steric and lipophilic parameters have a significant correlation (r(2)=0.85) with
      anti-inflammatory activity of the selected class of compounds. On the basis of
      results it may be suggested that the 1,3-diaryl-2-propen-1-ones framework is an
      attractive template for structural optimization to achieve better potency of anti
      inflammatory activity. Similarly, the relatively low correlation between anti
      inflammatory activity and cyclooxygenase-2 inhibition indicates that other modes
      of actions may also be responsible for the anti-inflammatory activity of the
      tested compounds.

PMID- 22615622
TI  - Preparation and in vitro antibacterial evaluation of gatifloxacin mucoadhesive
      gellan system.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: The poor bioavailability and therapeutic
      response exhibited by the conventional ophthalmic solutions due to precorneal
      elimination of the drug may be overcome by the use of mucoadhesive in situ gel
      forming systems that are instilled as drops into the eye and undergo a sol-gel
      transition in the cul-de-sac and have good mucoadhesion with ocular mucus layers.
      The objective of this study was to formulate ophthalmic mucoadhesive system of
      gatifloxacin (GTN) and to evaluate its in vitro antibacterial potential against,
      Staphylococcus aureus and Escherichia coli. METHODS: : Mucoadhesive systems were
      prepared using gellan combined with sodium carboxymethylcellulose (NaCMC) or
      sodium alginate to enhance the gel bioadhesion properties. The prepared
      formulations were evaluated for their gelation, and rheological behaviors,
      mucoadhesion force, in vitro drug release, and antibacterial activity. RESULTS:
      All formulations in non-physiological or physiological conditions showed
      pseudoplastic behaviors. Increase in the concentration of mucoadhesive agent
      enhanced the mucoadhesive force significantly. In vitro release of gatifloxacin
      from the mucoadhesive system in simulated tear fluid (STF, pH of 7.4) was
      influenced significantly by the properties and concentration of gellan, sodium
      carboxymethyl cellulose and sodium alginate. Significant reduction in the total
      bacterial count was observed between drug solution (control) and mucoadhesive
      batches against both tested organisms. MAJOR CONCLUSION: The developed
      mucoadhesive system is a viable alternative to conventional eye drops of GTN due
      to its ability to enhance bioavailability through its longer precorneal residence
      time and ability to sustain the release of the drug.

PMID- 22615623
TI  - Formulation and In Vitro evaluation of pH sensitive oil entrapped polymeric
      blended gellan gum buoyant beads of clarithromycin.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: A gastroretentive pH sensitive system
      has been a frontier approach to release the drug in controlled manner in stomach
      and duodenum. The aim of this study was to develop buoyant beads of gellan based,
      wherein, the oil was entrapped, blended with hydroxypropyl methyl cellulose or
      carbopol 934 in order to evaluate its potential for targeted sustained delivery
      of clarithromycin in the gastric region. METHODS: Buoyant beads of gellan was
      developed by inotropic gelation technique using calcium carbonate as gas forming
      agent and the drug polymer dispersion was emulsified with mineral oil. The oil
      was entrapped and blended with hydroxypropyl methyl cellulose or carbopol 934.
      The developed beads were evaluated in terms of diameter,% floating, encapsulation
      efficiency, In vitro drug release, In vivo gastric residence efficacy and
      clarithromycine concentration in the mucosa of the experimental animal model.
      RESULTS: The scanning electron microscope photograph indicated that the prepared
      beads were spherical in shape and buoyancy, encapsulation efficiency and drug
      content obtained from all batches were satisfactory. Particle size and percentage
      buoyancy of the gel beads increased by raising the concentration of calcium
      carbonate. The formulation exhibited sustained release profile and was best
      fitted in the Peppas model with n<0.45. Subsequent coating of microbeads
      exhibited zero-order sustained pattern of the drug release up to 8 hrs. Batch
      B(4) showed comparatively better residence and the drug concentration in the
      gastric mucosa of the treated animals. CONCLUSION: The result provides evidence
      that the prepared optimized formulation may be used effectively for pH sensitive
      gastric targeted antibiotic such as clarithromycin.

PMID- 22615624
TI  - Effect of pomegranate juice pre-treatment on the transport of carbamazepine
      across rat intestine.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Many drug substances along with a
      variety of naturally occurring dietary or herbal components interact with the CYP
      enzyme system. The present study was aimed to investigate the effect of
      pomegranate juice pre-treatment on the transport of carbamazepine across the rat
      intestine. METHODS: The transport of carbamazepine across different parts of rat
      intestine was studied by everted and non-everted sac methods. The control and
      pomegranate juice (10 ml Kg(-1) for 7 days) pre-treated rats were sacrificed and
      isolated the intestine. The sacs of intestine were prepared, treated with
      carbamazepine solution and then placed in dulbeccos buffer. Samples were
      collected periodically and the drug content was estimated using HPLC. RESULTS AND
      CONCLUSION: The results show that there was a significant (p<0.05) difference in
      the transport of carbamazepine from the intestinal sacs of pretreated with
      pomegranate juice and control. It seems that pomegranate juice might have induced
      CYP3A4 enzymes and hence drug is extensively metabolized.

PMID- 22615625
TI  - Effects of Angipars on oxidative inflammatory indices in a murine model of
      periodontitis.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: There are strong evidences linking
      overproduction of reactive oxygen species and periodontal diseases. The aim of
      this study was to evaluate efficacy of Angipars a natural potent anti oxidative
      agent on markers of the oxidative damages and periodontal inflammation in the
      rat. METHODS: Periodontitis was induced by single injection of lipopolysaccharide
      (LPS) from E. coli (10 ug/ul saline) into rat mandibular gingiva. After 10 days,
      animals in the test group received Angipars (2.1 mg/kg) by gavage once a day and
      those of control group received same amount of vehicle. The amount of interleukin
      (IL)-1beta, lipid peroxidation (LPO), and 8-hydroxydeoxyguanosine (8-OHdG) were
      measured in gingival biopsy samples and the degree of apical migration of
      junctional epithelium (JE), alveolar bone resorption, and the number of
      polymorphonuclears (PMN) were evaluated by histological analysis of block samples
      of the left mandibular first molars. RESULTS: Periodontitis group showed a
      significant increase in periodontal IL-1beta, LPO, 8-OHdG, apical migration of
      JE, alveolar bone resorption and number of PMNs. Angipars treatment resulted in a
      significant decrease in gingival IL-1beta, LPO, 8-OHdG and the apical migration
      of JE; however, the reduction of alveolar bone resorption was not significant.
      The number of PMN increased significantly after treatment with Angipars. While
      intake of vehicle resulted in a significant decrease in gingival IL-1beta and
      LPO, the reduction of 8-OHdG, apical migration of JE, and alveolar bone
      resorption were not significant. Interestingly, PMNs were increased in groups
      received Angipars or the vehicle. CONCLUSION: From the results of this study, it
      seems that Angipars is beneficial in periodontitis by reduction of inflammatory
      and oxidative damage. Unexpected increase of PMN count by Angipars strengthens
      the hypothesis that chronic inflammatory disorders like periodontitis may need
      more time to get best advantage of anti oxidative drugs like Angipars. Regarding
      role of microbes in pathogenesis of periodontitis, further studies should be
      focused on antimicrobial effects of Angipars.

PMID- 22615626
TI  - Effects of Semelil (ANGIPARSTM) on focal cerebral ischemia in male rats.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Cerebral ischemia is one of the main
      causes of long term disability and death in aged populations. Many herbal drugs
      and extracts have been used for the treatment of cerebral ischemia induced
      insults. This study was designed to investigate the protective effect of Semelil
      (ANGIPARSTM), a new herbal drug, on focal cerebral ischemia in male rats.
      MATERIAL AND METHODS: MALE RATS WERE DIVIDED INTO FIVE GROUPS: sham-operated,
      ischemic animals treated with distilled water as vehicle, ischemic animals
      treated with 1, 10 and 100 mg/kg of Semilil respectively. Middle cerebral artery
      occlusion (MCAO) model was used in NMRI rats and neuronal injury analyzed in
      hippocampal CA1 sector after 48 hrs of Middle Cerebral Artery (MCAO). RESULTS:
      Results of this study showed that treatment with semelil attenuated ischemic
      damages and has positive effects on focal cerebral ischemia.

PMID- 22615627
TI  - Antidiabetic properties of the ethanolic extract of Rhus coriaria fruits in rats.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Fruits of Rhus coriaria L.
      (Anacardiaceae) are traditionally used as a table spice in Iran and are highly
      recommended for diabetic patients. The purpose of this study was to determine the
      antidiabetic properties of the ethanolic extract of Rhus coriaria fruits and also
      its mechanisms of action. METHODS: The effects of ethanolic extract of Rhus
      coriaria fruits were measured on blood glucose, lipids and antioxidant enzymes by
      commercial kits. mRNA levels of insulin (INS) and glucose transporter type-4
      (GLUT-4) genes were investigated by RT-PCR (Reverse transcription- polymerase
      chain reaction) technique. Moreover, its effects on intestinal a-glucosidases was
      measured using an in vitro method. RESULTS AND CONCLUSION: Following a single
      dose administration of the extract it was found that extract could significantly
      reduce postprandial blood glucose by 24% (at 5 hrs). In the long term experiment,
      on the day of 21, postprandial blood glucose (PBG) was found to be significantly
      lower (by 26%) compared to diabetic control group. The plant extract raised
      markedly serum high-density lipoprotein (HDL) by 34% and also reduced low-density
      lipoprotein (HDL) by 32%. Also it had noticeable antioxidant effects by elevating
      superoxide dismutase (SOD) and catalase(CAT) activities by 46% and 77%,
      respectively. However it did not show a strong effect on glutathione peroxidase
      (GPX) activity. The extract inhibited maltase and sucrase activities by 44% and
      27%, respectively. However it made no changes in the transcript levels of INS and
      GLUT-4 genes. It can be concluded that constituents of Rhus coriaria fruits have
      effective components which can be utilized as useful herb for alleviation of
      diabetes complications.

PMID- 22615628
TI  - Upregulation of the ERG11 gene in Candida krusei by azoles.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Candida species are the agents of local
      and systemic opportunistic infections and have become a major cause of morbidity
      and mortality in the last few decades. Azole resistance in Candida krusei (C.
      krusei) species appears to be the result of gene alterations in relation to the
      ergosterol biosynthesis pathway, as well as efflux pumps. The main objective of
      this study was to examine the RNA expression of ERG11 in C. krusei which had been
      identified to be resistance to azoles. METHODS: The ERG11 mRNA expression was
      investigated in four Iranian clinical isolates of C. krusei, which were resistant
      to fluconazole and itraconazole by a semiquantitative RT-PCR. RESULTS: The mRNA
      expression levels were observed in all four isolates by this technique.
      Furthermore, it was found that ERG11 expression levels vary among four
      representative isolates of C. krusei. Although DNA sequencing revealed no
      significant genetic alteration in the ERG11 gene, one heterozygous polymorphism
      was observed in two isolates, but not in others. This polymorphism was found in
      the third base of codon 313 for Thr (ACT>ACC). MAJOR CONCLUSION: Even though such
      a polymorphism creates a new Ear1 restriction site, no significant effect was
      found on the resistance of C. krusei to azoles. RESULTS of this investigation are
      consistent with previous studies and may provide further evidence for the genetic
      heterogeneity and complexity of the ergosterol biosynthetic pathway or efflux
      pumps.

PMID- 22615629
TI  - Cloning and expression of human vascular endothelial growth factor gene and
      inhibition of its expression by antisense in prokaryotic system.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Angiogenesis is an important process in
      physiology and disease pathogenesis and is controlled in a healthy body by a
      number of stimulatory and inhibitory factors. The aim of this study was to
      determine the effect of antisense transcript on the sense transcript of the
      endothelial growth factor (EGF) gene in bacterial system as an approach for the
      gene regulation in tumors. METHODS: The hepatoma cell line (HepG2) was stimulated
      by PMA. VEGF mRNA was used for RT-PCR. VEGF cDNA was synthesised and cloned into
      T-vector pTZ57R, then sense fragment of VEGF subcloned into pACYC Duet-1
      expression vector and antisense VEGF subcloned into pCDNA3 expression vector.
      Recombinant plasmids were transforemed into BL21 bacterial cells. Expression of
      recombinant plasmid was analysed by western blot technique. RESULTS: The
      recombinant pCDNA3-VEGF (pYZantiVEGF) was successfully expressed in BL21 cells.
      Western blot analysis showed that the expression of VEGF decreased significantly
      in the cells transfected with VEGF antisense RNA compared with the pACYCDUET-1
      VEGF (pYZsenseVEGF) transfected and control. MAJOR CONCLUSIONS: The expression of
      VEGF in BL21 cells was strong. In vitro, antisense of VEGF inhibited VEGF
      expression significantly in BL21 cells.

PMID- 22615630
TI  - Mutation of the histidin residue of the DRH motif in vasopressin V2 receptor
      expression and function.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Vasopressin type 2 receptor (V2R), a G
      protein coupled receptor (GPCR), plays an important role in the regulation of
      renal antidiuretic function. The highly conserved DRH motif is essential for G
      protein signaling of V2R; however its role especially regarding the histidin
      residue is not fully understood.. METHODS: Site directed mutagenesis was
      performed with replacements of the histidin to isoleucine by using nested
      polymerase chain reaction. ELISA was performed for receptor expression assay and
      the adenylyl cyclase activity assay was performed for functional characterization
      of DRI mutation on V2R signaling. RESULTS AND MAJOR CONCLUSION: The adenylyl
      cyclase activity assay in COS-7 cells showed no difference in the amount of cAMP
      production between the wild type and the mutant V2 receptors. The V2 receptor
      expression was not changed in the presence of this mutation using ELISA assay.
      These results suggest that the role of histidin residue is not critical in the V2
      receptor function, however further mutagenesis studies are required to define the
      role of this motif in V2R function.

PMID- 22615631
TI  - Simultaneous spectrophotometric determination of paracetamol, phenylephrine and
      chlropheniramine in pharmaceuticals using chemometric approaches.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: The linear multivariate calibration
      models such as principal components regression (PCR) and partial least squares
      regressions (PLS1 and PLS2) due to the mathematical simplicity and physical or
      chemical interpretability are sufficient and generally preferred method for
      analysis of multicomponent drugs. In this study, simultaneous determination of
      paracetamol, phenylephrine and chlorpheniramine in pharmaceuticals using
      chemometric methods and UV spectrophotometry is reported as a simple alternative
      technique. MATERIAL AND METHODS: Principal components regression (PCR) and
      partial least squares regressions (PLS1 and PLS2) were used for chemometric
      analyses of data obtained from the spectra of paracetamol, phenylephrine and
      chlorpheniramine between wavelengths of 200 to 400 nm at several concentrations
      within their linear ranges. The analytical performance of these chemometric
      methods were characterized by relative prediction errors and recoveries (%) and
      compared with each other. RESULTS: PCR, PLS1 and PLS2 were successfully applied
      to a tablet formulation, with no interference from excipients as indicated by the
      recovery. However, the PLS1 shows better results due to its flexibility and
      mathematical principals. CONCLUSION: The proposed methods are simple and rapid
      requiring no separation step, and can be easily used as an alternative in the
      quality control of drugs.

PMID- 22615632
TI  - Fentanyl supplement expedites the onset time of sensory and motor blocking in
      interscalene lidocaine anesthesia.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Opioids are usually used in regional
      anesthesia, with or without local anesthetics to improve the regional block or
      postoperative pain control. Since no data are available on fentanyl's effect on
      the onset time of lidocaine interscalene anesthesia, the purpose of this study
      was to examine its effect on the onset time of sensory and motor blockade during
      interscalene anesthesia. METHODS: In a prospective, randomized, double-blind
      study, ninety patients scheduled for elective shoulder, arm and forearm surgeries
      under an interscalene brachial plexus block.They were randomly allocated to
      receive either 30 ml of 1.5% lidocaine with 1.5 ml of isotonic saline (control
      group, n=39) or 30 ml of 1.5% lidocaine with 1.5 ml (75 ug) of fentanyl (fentanyl
      group, n=41). Then the onset time of sensory and motor blockades of the shoulder,
      arm and forearm were evaluated every 60 sec. The onset time of the sensory and
      motor blockades was defined as the time between the last injection and the total
      abolition of the pinprick response and complete paralysis. The duration of
      sensory blocks were considered as the time interval between the administration of
      the local anesthetic and the first postoperative pain sensation. RESULTS: Ten
      patients were excluded because of unsuccessful blockade or unbearable pain during
      the surgery. The onset time of the sensory block was significantly faster in the
      fentanyl group (186.54+/-62.71sec) compared with the control group (289.51+/
      81.22, P<0.01). The onset times of the motor block up to complete paralysis in
      forearm flexion was significantly faster in the fentanyl group (260.61+/
      119.91sec) than the control group (367.08+/-162.43sec, P<0.01). There was no
      difference in the duration of the sensory block between two groups. CONCLUSION:
      Results of the study showed that the combination of 75 ug fentanyl and 1.5%
      lidocaine solution accelerated the onset of sensory and motor blockade during
      interscalene anesthesia.

PMID- 22615633
TI  - Effects of arsenic trioxide, all-trans-retinoic acid and dexamethasone on NB4
      cell line.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Experimental and preclinical
      observations have indicated that combination therapy with all-trans-retinoic acid
      (ATRA) and arsenic trioxide (ATO) may strongly enhance their therapeutic effects
      in the treatment of acute promyelocytic leukemia (APL). Whilst dexamethasone
      (Dex) is routinely used for the control of APL- differentiation syndrome, its
      effect on the pharmacodynamics of ATO is not clear. Therefore, in this study,
      effects of therapeutic concentrations of ATO, ATRA and Dex and their sequential
      usages on the proliferation, differentiation and apoptosis in t(15;17)-positive
      NB4 cells was investigated. METHODS: Cells were treated with therapeutic
      concentrations of ATO, ATRA and Dex either as single or in combination and cell
      proliferation was assessed by XTT assay. Expression of CD11b as an indicator of
      cell differentiation and the percentage of 7-AAD positive cells as a marker of
      apoptosis were determined by flow cytometry. RESULTS: ATO, but not ATRA and Dex,
      decreased proliferation of the cells dose-dependently. Pre-treatment of the cells
      with any of the drugs did not alter the effects of other drugs on the
      proliferation. Pre-treatments with Dex blocked the apoptotic effect of ATO (1
      uM). CONCLUSION: No improvement or antagonistic effects was observed with the
      pretreatment/ combination of the ATO and ATRA on the differentiation and
      apoptosis of the cells. It is possible that concomitant usage of Dex with
      apoptotic doses of ATO in APL patients counteract therapeutic effects of ATO.

PMID- 22615634
TI  - Angelica archengelica extract induced perturbation of rat skin and tight
      junctional protein (ZO-1) of HaCaT cells.
AB  - BACKGROUND AND PURPOSE OF THE STUDY: Herbal enhancers compared to the synthetic
      ones have shown less toxis effects. Coumarins have been shown at concentrations
      inhibiting phospoliphase C-Y (Phc-Y) are able to enhance tight junction (TJ)
      permeability due to hyperpoalation of Zonolous Occludense-1 (ZO-1) proteins. The
      purpose of this study was to evaluate the influence of ethanolic extract of
      Angelica archengelica (AA-E) which contain coumarin on permeation of repaglinide
      across rat epidermis and on the tight junction plaque protein ZO-1 in HaCaT
      cells. METHODS: Transepidermal water loss (TEWL) from the rat skin treated with
      different concentrations of AA-E was assessed by Tewameter. Scanning and
      Transmission Electron Microscopy (TEM) on were performed on AA-E treated rat skin
      portions. The possibility of AA-E influence on the architecture of tight
      junctions by adverse effect on the cytoplasmic ZO-1 in HaCaT cells was
      investigated. Finally, the systemic delivery of repaglinide from the optimized
      transdermal formulation was investigated in rats. RESULTS: The permeation of
      repaglinide across excised rat epidermis was 7-fold higher in the presence of AA
      E (5% w/v) as compared to propylene glycol:ethanol (7:3) mixture. The extract was
      found to perturb the lipid microconstituents in both excised and viable rat skin,
      although, the effect was less intense in the later. The enhanced permeation of
      repaglinide across rat epidermis excised after treatment with AA-E (5% w/v) for
      different periods was in concordance with the high TEWL values of similarly
      treated viable rat skin. Further, the observed increase in intercellular space,
      disordering of lipid structure and corneocyte detachment indicated considerable
      effect on the ultrastructure of rat epidermis. Treatment of HaCaT cell line with
      AA-E (0.16% w/v) for 6 hrs influenced ZO-1 as evidenced by reduced
      immunofluorescence of anti-TJP1 (ZO-1) antibody in Confocal Laser Scanning
      Microscopy studies (CLSM) studies. The plasma concentration of repaglinide from
      transdermal formulation was maintained higher and for longer time as compared to
      oral administration of repaglinide. MAJOR CONCLUSION: Results suggest the
      overwhelming influence of Angelica archengelica in enhancing the percutaneous
      permeation of repaglinide to be mediated through perturbation of skin lipids and
      tight junction protein (ZO-1).

PMID- 22615635
TI  - Preparation and evaluation of poly (caprolactone fumarate) nanoparticles
      containing doxorubicin HCI.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Biodegradable Poly(caprolactone
      fumarate) (PCLF) has been used as bioresorbable sutures. In this study,
      doxorubicin HCl (Dox) loaded PCLF nanoparticles were prepared and characterized.
      MATERIAL AND METHODS: PCLFs were synthesized by polycondensation of PCL diols
      (Mws of 530, 1250 and 2000) with fumaryl chloride. The degradation of PCLF in
      NaOH, water and phosphate buffer saline (PBS), was determined in terms of changes
      in Mw. Nanoparticles (NPs) were prepared by two methods. In microemulsion
      polymerization method, dichloromethane containing PCLF and photoinitiator were
      combined with the water containing surfactants and then the mixture was placed
      under light for crosslinking. In nanoprecipitation method, the organic solvent
      containing PCLF was poured into the stirring water. The effect of several
      variables including concentration of PCLF, polyvinyl alcohol (PVA), Dox and
      Trypan blue (Trb) and the Mw of PCLF and PVA on NP size and loading were
      evaluated. RESULT: PCLF 530, 1250 and 2000 in PBS or water were not degraded over
      28 days. Nanoprecipitaion method gave spherical (revealed by SEM images) stable
      NPs of about 225 with narrow size distribution and a zeta potential of -43 mV.
      The size of NP increased significantly by increase in Mw or concentration of
      PCLF. Although PVA was not necessary for formation of NPs, but it decreased with
      NP size. Dox loading and EE were 2.5-6.8% and 15-20%, respectively. Increasing
      the drug concentration increased the drug loading (DL) and NP size. The
      entrapment efficiency (EE) for Trb ranged from 1% for PCLF530 to 6% for PCLF2000.
      An increase in PCLF concentration resulted in an increase in EE. Dox and Trb
      release showed a burst followed by 80% and 78% release during 3 and 4 days
      respectively. CONCLUSION: PCLF possessed suitable characteristics for preparation
      of nanoparticulate drug delivery system such as desired NP size, stability and
      degradation time. Although PCLF530 NPs were the smallest, but their DL were lower
      than PCLF1250 and 2000 NPs.

PMID- 22615636
TI  - Formulation and in vitro characterization of domperidone loaded solid lipid
      nanoparticles and nanostructured lipid carriers.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Domperidone (DOM) is a dopamine-
      receptor (D(2)) antagonist, widely used in the treatment of motion-sickness. The
      pharmacokinetic parameters of DOM make it a suitable candidate for development of
      Solid Lipid Nanoparticle (SLN) and Nanostructured Lipide Carrier (NLC). The
      purpose of the present investigation was to prepare and evaluate DOM loaded solid
      lipid nanoparticles (DOM-SLN) and DOM loaded nanostructured lipid carriers (DOM
      NLC). METHODS: DOM loaded SLN and NLC were prepared by hot homogenization
      followed by ultrasonication technique, using trimyristin as solid lipid, cetyl
      recinoleate as liquid lipid and a mixture of soy phosphatidylcholine (99%) and
      tween 80 as surfactant. SLN and NLC were characterized for particle size,
      polydispersity index (PDI), zeta potential and entrapment efficiency. The effects
      of composition of lipid materials and surfactant mixture on the particle size,
      PDI, zeta potential, drug entrapment efficiency, and in vitro drug release
      behavior were investigated. DSC analysis was performed to characterize the state
      of drug and lipid modification. Shape and surface morphology were determined by
      transmission electron microscopy (TEM). SLN and NLC formulations were subjected
      to stability study over a period of 40 days. RESULTS: The mean particle size,
      PDI, zeta potential and entrapment efficiency of optimized SLN (SLN1) and NLC
      were found to be 30.45 nm, 0.156, 12.40 mV, 87.84% and 32.23 nm, 0.160, 10.47 mV,
      90.49% respectively. DSC studies revealed that DOM was in an amorphous state and
      triglycerides were in the beta prime form in SLN and NLC. Shape and surface
      morphology was determined by TEM revealed fairly spherical shape of
      nanoparticles. In vitro release studies demonstrated that both the SLN and NLC
      formulations possessed a controlled release over a period of 24 hrs. SLN and NLC
      formulations were subjected to stability over a period of 40 days. There was no
      significant (P<0.05) change in particle size, zeta potential, PDI and entrapment
      efficiency indicating the developed SLN and NLC were fairly stable. CONCLUSION:
      Fairly spherical shaped, stable and controlled release DOM-SLN and DOM-NLC could
      be prepared by hot homogenization followed by ultrasonication technique.

PMID- 22615637
TI  - Formulation and in vitro characterization of cefpodoxime proxetil gastroretentive
      microballoons.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: The objective of the present work was to
      improve bioavailability of cepodoxime proxetil through gastroretentive
      microballoon formulation. METHODS: Microballoons of cefpodoxime proxetil were
      formulated by solvent evaporation and diffusion method employing
      hydroxypropylmethyl cellulose (HPMC) and ethyl cellulose (EC) polymers and
      characterized for particle size, surface morphology, incorporation efficiency,
      floating behavior, in vitro drug release study and differential scanning
      calorimetry (DSC). RESULTS: The average particle size of formulated microballoons
      was in the range of 54.23+/-2.78-95.66+/-2.19um. Incorporation efficiencies of
      over 83.77+/-0.85% were achieved for the optimized formulations. Most of
      formulations remained buoyant (having buoyancy percentage maximum of 81.36+/
      1.96%) for more than 12 hrs indicating good floating behavior of microballoons.
      Higher values of correlation coefficients were obtained with Higuchi's square
      root of time kinetic treatment heralding diffusion as predominant mechanism of
      drug release. CONCLUSION: Inferences drawn from in vitro studies suggest that
      microballoons may be potential delivery system for cefpodoxime proxetil with
      improvement in bioavailability in comparison to conventional dosage forms.

PMID- 22615638
TI  - Multilayered membrane-controlled microcapsules for controlled delivery of
      isoniazid.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Layer-by-layer (LbL) deposition of
      polyelectrolytes (PEs) has received a great attention in the area of drug
      delivery due to its simplicity and versatility. This research was aimed to
      develop multilayered microcapsules through LbL deposition of chitosan (CHI) and
      sodium alginate (NaALG) and utilize them as vehicle for controlled delivery of
      isoniazid (INH). METHODS: CaCO(3) particles, prepared by colloidal
      crystallization of CaCl(2) and Na(2)CO(3) solutions, were used as micro-templates
      for LbL deposition of CHI and NaALG. Subsequent to the deposition, templates were
      decomposed to obtain hollow microcapsules. Prepared microcapsules were subjected
      to physicochemical evaluations, drug release and stability studies. RESULTS AND
      MAJOR CONCLUSION: Though CaCO(3) particles possessed a rough and irregular
      surface, prepared hollow microcapsules were spherical in shape, having smooth
      surface and regular thickness. Following deposition of each layer, alternating
      values of zeta potential were observed, indicating the formation of multilayered
      films. Microcapsules with 5 bilayers, i.e. (CHI/NaALG)(5) provided 39% entrapment
      efficiency and exhibited a controlled release behavior, lasting up to 24 hrs. An
      improvement in drug release rate and stability profile of the formulation was
      observed by increasing the number of deposition steps and performing the
      crosslinking of polyelectrolytes. This study showed that the prepared formulation
      could promisingly be utilized as controlled delivery vehicle for INH.

PMID- 22615639
TI  - Preparation and gamma scintigraphic evaluation of colon specific pellets of
      ketoprofen prepared by powder layering technology.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Multiparticulates by powder layering
      process have advantages of the uniform distribution of the binder solution, easy
      to-clean pan and the possibility of applying the successive functional film
      coating using the same equipment. This study relates to a multiparticulate
      formulation comprising pellets with a multilayer of pectin-ethyl cellulose on non
      pareil seeds by powder layering technology. The pellets were prepared to target
      ketoprofen in colon based on the microbial enzyme dependent drug release
      mechanism. METHODS: Multiparticulate formulation by powder layering technology
      was prepared by conventional pan coating process to evaluate the effect of 59%
      methoxylated pectin and 45 cps ethyl cellulose on coating label. The formulations
      were tagged with (99m)Tc-DTPA, a tracer in gamma scintigraphy study to evaluate
      the transit behavior of drug loaded pellets and compared with uncoated pellets to
      evaluate its specific release. RESULTS: The transit behavior and scintigraphy
      image clearly indicates that the formulation can delay the drug release prior to
      colon. In albino rabbit, the coated pellets released drug in the colon indicating
      that site specificity has been achieved with pectin/ethyl cellulose coating at
      1:2 ratio with 20% coating label. MAJOR CONCLUSION: Formulation containing pectin
      and ethyl cellulose with suitable coating label may be suitable as a coating
      formulation for colon delivery of ketoprofen and can be successfully evaluated by
      gamma scintigraphy method.

PMID- 22615640
TI  - Improved bioavailability through floating microspheres of lovastatin.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Lovastatin is an antihyperlipidemic
      agent which has low bioavailability due to the extensive first pass metabolism.
      It was sought to increase gastric retention of lovastatin by development of a
      sustained release gastroretentive drug delivery system leading to reduced
      fluctuation in the plasma concentration and improved bioavailability.  MEHODS:
      Floating microspheres were prepared by emulsion solvent diffusion technique,
      using various polymers and their blends. The in vitro performance was evaluated
      for drug-polymer compatibility, percent yield, particle size, drug entrapment
      efficiency, in vitro onset and duration of floatation, in vitro drug release as
      well as in vivo determination of serum cholesterol level. RESULTS: The mean
      particle size of microspheres was observed to be between 6.9 to 9.5 um and the
      maximum particle size was around 50 um. In vivo studies of the selected batches
      indicated lower level of serum cholesterol compared to the marketed tablet at the
      same dose but was not significant. MAJOR CONCLUSION: The data obtained in this
      study suggested that a microparticulate floating dosage form of lovastatin can be
      successfully designed to yield controlled delivery with improved therapeutic
      efficacy.

PMID- 22615641
TI  - Effects of Semelil (ANGIPARSTM) on diabetic peripheral neuropathy: A randomized,
      double-blind Placebo-controlled clinical trial.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Diabetic neuropathy is the most common
      diabetic complication that often is accompanied by significant morbidity,
      mortality and economic burden. The purpose of this study was evaluation of effect
      of Semelil (ANGIPARSTM), a new herbal drug for treatment of diabetic foot ulcers
      or diabetic peripheral neuropathy. METHODS: In this double blind clinical trial,
      49 type 2 diabetes patients with different degrees of neuropathy were evaluated
      in two groups (ANGIPARSTM and placebo groups). All patients were assessed at the
      start and 12 weeks after treatment, with laboratory tests, United Kingdom
      screening test, Michigan neuropathy screening score, Michigan diabetic neuropathy
      score, vibration perception thresholds, nerve conduction study, monofilament test
      and visual analog scale. RESULTS: Michigan diabetic neuropathy score was
      decreased notably in ANGIPARSTM group. In the nerve conduction study, appropriate
      meaningful changes were observed in the distal latency and amplitude in the motor
      Ulnar nerve in ANGIPARSTM group. CONCLUSION: The results showed limited evidence
      of efficacy of ANGIPARSTM in diabetic neuropathy treatment and more studies with
      a larger sample size and longer duration are required.

PMID- 22615642
TI  - A comparison between zinc sulfate and chlorhexidine gluconate mouthwashes in the
      prevention of chemotherapy-induced oral mucositis.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Patients undergoing high-dose
      chemotherapy for hematological malignancies are susceptible to development of
      oral mucositis, and no effective modality has been reported for its prophylaxis
      and treatment. The aim of this study was to evaluate the effectiveness of zinc
      mouthwash on chemotherapy-induced oral mucositis lesions. METHODS: In this double
      blind randomized trial, patients under chemotherapy for acute leukemia were
      divided into two test and control groups of 15 patients each. The groups were
      homogeneous with respect to medical history, tumor characteristics, and
      therapeutic details. The test group received 10ml 0.2% zinc sulfate mouthwash,
      and the control group received 10ml 0.2% chlorhexidine gluconate mouthwash, twice
      a day for a period of two weeks. Spijkervet scale was used to grade the severity
      of mucositis at every other week during eight weeks. The severity scores were
      analyzed with repeated measure ANOVA using SPSS 13.0 computer software. RESULTS:
      Mean severity scores were generally lower in the test group compared to the
      controls at all four time intervals evaluated; but only, the differences in weeks
      of 2 and 3 were statistically significant (P=0.025). CONCLUSION: Zinc mouthwash
      used in conjunction with chemotherapy may reduce the severity of oral mucositis
      lesions in patients with leukaemia.

PMID- 22615643
TI  - Lignans and neolignans from Stelleropsis antoninae.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Stelleropsis antoninae Pobed. (Family:
      Thymelaeaceae) grows wildly as an herbaceous plant in Iran. Most of the
      Thymelaeaceous plants contain lignans and neolignans, which have important
      pharmacologically properties. In the present study, the isolation and
      identification of the main lignans and neolignans of S. antoninae, which has not
      been previously reported is described and compared to other species. METHODS:
      Column (CC) and High Performance Liquid Chromatographic (HPLC) methods were used
      for the isolation and purification, and (1)H-NMR, (13)C-NMR, HMBC, HMQC, H-H COSY
      and MS were employed for the identification of the compounds isolated from the
      methanol extract. RESULTS: From the methanol extract of the aerial parts of S.
      antoninae four lignans, syringaresinol (1), syringaresinol 4-O-beta-D
      glucopyranoside (4), syringaresinol 4-O-beta-D-glucopyranosyl-(1->6)-beta-D
      glucopyranoside (5), liriodendrin (6), and two neolignans, 5-methoxylariciresinol
      4'-O- beta-D-glucopyranoside (3) and dehydrodiconiferyl alcohol 4-O-beta -D
      glucopyranoside (2) were isolated and identified. MAJOR CONCLUSION: The results
      of this study show that siringaresinol, a well-known bioavtive compound, and its
      glucosides are the main lignans, and lariciresinol and coniferyl alcohol
      derivatives are the main neolignans of S. antoninae.

PMID- 22615644
TI  - Perspective of pharmaceutical sciences in Iran; Jobs remaining.
AB  - Iran is growing fast in production of science and technology in the world. Based
      on experts' opinion and reports of the Institute for Scientific Information
      (ISI), SCImago Journal and Country Rank, and Scopus it is concluded that the
      scientific field of Pharmacology Toxicology Pharmaceutics in Iran is growing very
      fast with great impact on the country science growth. Regarding various elements
      that have been involved in growth of sciences in Iran, focusing on quality of
      researches by the proposed methods in the present essay would be the key element
      of success in future.

PMID- 22615645
TI  - Evaluation of the use of partition coefficients and molecular surface properties
      as predictors of drug absorption: a provisional biopharmaceutical classification
      of the list of national essential medicines of Pakistan.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Partition coefficients (log D and log P)
      and molecular surface area (PSA) are potential predictors of the intestinal
      permeability of drugs. The aim of this investigation was to evaluate and compare
      these intestinal permeability indicators. METHODS: Aqueous solubility data were
      obtained from literature or calculated using ACD/Labs and ALOGPS. Permeability
      data were predicted based on log P, log D at pH 6.0 (log D(6.0)), and PSA.
      RESULTS: Metoprolol's log P, log D(6.0,) and a PSA of <65 A correctly predicted
      55.9%, 50.8% and 54.2% of permeability classes, respectively. Labetalol's log P,
      log D(6.0) and PSA correctly predicted 54.2%, 64.4% and 61% of permeability
      classes, respectively. Log D(6.0) correlated well (81%) with Caco-2 permeability
      (P(app)). Of the list of national essential medicines, 135 orally administered
      drugs were classified into biopharmaceutical classification system (BCS). Of
      these, 57 (42.2%), 28 (20.7%), 44 (32.6%), and 6 (4.4%) were class I, II, III and
      IV respectively. CONCLUSION: Log D(6.0) showed better prediction capability than
      log P. Metoprolol as permeability internal standard was more conservative than
      labetalol.

PMID- 22615646
TI  - Comparison of physicomechanical properties of films prepared from organic
      solutions and aqueous dispersion of Eudragit RL.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Mechanical properties of films prepared
      from aqueous dispersion and organic solutions of Eudragit RL were assessed and
      the effects of plasticizer type, concentration and curing were examined. METHODS:
      Films were prepared from aqueous dispersion and solutions of Eudragit RL
      (isopropy alcohol-water 9:1) containing 0, 10 or 20% (based on polymer weight) of
      PEG 400 or Triethyl Citrate (TEC) as plasticizer using casting method. Samples of
      films were stored in oven at 60 degrees C for 24 hrs (Cured). The stress-strain
      curve was obtained for each film using material testing machine and tensile
      strength, elastic modulus, %elongation and work of failure were calculated.
      RESULTS AND MAJOR CONCLUSION: The films with no plasticizer showed different
      mechanical properties depending on the vehicle used. Addition of 10% or 20% of
      plasticizer decreased the tensile strength and elastic modulus and increased
      %elongation and work of failure for all films. The effect of PEG 400 on
      mechanical properties of Eudragit RL films was more pronounced. The differences
      in mechanical properties of the films due to vehicle decreased with addition of
      plasticizer and increase in its concentration. Curing process weakened the
      mechanical properties of the films with no plasticizer and for films with 10%
      plasticizer no considerable difference in mechanical properties was observed
      before and after curing. For those with 20% plasticizer only films prepared from
      aqueous dispersion showed remarkable difference in mechanical properties before
      and after curing. Results of this study suggest that the mechanical properties of
      the Eudragit RL films were affected by the vehicle, type of plasticizer and its
      concentration in the coating liquid.

PMID- 22615647
TI  - Development of novel budesonide pellets based on CODES(TM) technology: In
      vitro/in vivo evaluation in induced colitis in rats.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Budesonide is the drug of choice for
      treatment of active inflammatory bowel disease (IBD). The aim of this study was
      to develop budesonide pellets based on a novel colon drug delivery system
      (CODES). METHODS: Pellet cores containing lactulose or mannitol were prepared by
      extrusion/spheronization and coated with an acid soluble polymer (Eudragit E100),
      hydroxypropylmethyl cellulose (HPMC) and an enteric coat (Eudragit FS 30D)
      sequentially. In vitro drug release of coated pellets was studied using USP
      dissolution apparatus type II in buffers of pH 1.2 (2 hrs), pH of 7.4 (4 hrs) and
      pH of 6.8 containing 8% rat cecal contents (RCC) (18 hrs). The efficacy of the
      optimized formulation (containing 50% lactulose coated with Eudragit E (30% w/w)
      and Eudragit FS 30D (12% w/w)) was evaluated against 2, 4, 6
      trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. RESULTS: The results
      of the kind of bacteria in vitro dissolution tests indicated absence of drug
      release in pHs of 1.2 and 7.4 and controlled release in buffer of pH 6.8
      containing RCC. It was found that release rate was controlled by the type and
      amount of polysaccharide and the thickness of the acid soluble layer. The
      prepared formulation showed promising results in alleviating the conditions of
      experimental model of colitis. CONCLUSION: The results of this study suggest that
      pellets based on CODES technology could be useful for colonic delivery of
      budesonide.

PMID- 22615648
TI  - Formulation development and rheological studies of palatable cefetamet pivoxil
      hydrochloride dry powder suspension.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Because of its intense bitter taste and
      susceptibility to moisture Cefetamet Pivoxil (CPH) is presently available only in
      the form of tablet. The aim of this study was to develop taste masked CPH dry
      powder suspension. METHODS: METHODS EMPLOYED FOR FORMULATIONS WERE: a) Film
      coating of CPH using Eudragit E100 and subsequent adsorption on different
      carriers such as spray-dried lactose, sodium starch glycolate and spray-dried
      mannitol and b) Complexation of CPH with three different ion exchange resins
      indion 234 amberlite IRP64 and amberlite IRP69. RESULTS: Taste viz evaluation as
      recognized by volunteers revealed that coating with Eudragit E100 and subsequent
      adsorption on different carriers do not mask the bitter taste of the drug.
      Suspensions prepared using amberlite IRP64 and amberlite IRP69 were extremely
      palatable with no bitter after taste. They showed pseudoplastic flow behavior and
      were too viscous even after shearing for sufficient duration of time and
      exhibited poor pourability. The suspension made with indion 234 was palatable
      with slight or no bitter after taste. It demonstrated plastic flow with
      negligible thixotropy. It had moderate viscosity at rest and could be poured
      after a reasonable amount of shaking. CPH dry powder suspensions were very
      unstable under different conditions except under refrigeration. A 5% degradation
      of drug was occurred in reconstituted suspension in 4 days period when stored at
      room temperature. CONCLUSION: Dry powder suspension prepared with indion 234
      having 5% overages was stable even after 4th day of reconstitution and palatable
      with slight or no bitter after taste.

PMID- 22615649
TI  - Design of a controlled release liquid formulation of lamotrigine.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Lamotrigine is a broad spectrum
      anticonvulsant drug widely used as mono- or adjunct- therapy in adults and
      children. The aim of this study was to develop controlled release liquid
      formulation of lamotrigine to improve bioavailability and compliance of pediatric
      and geriatric epileptic patients. METHODS: Multiple (w/o/w) emulsion was prepared
      using one step emulsification technique. It was evaluated for entrapment
      efficiency (EE), morphology, zeta potential (ZP), polydispersity index (PI),
      rheology, thermal property, in vitro drug release behavior and stability. In vivo
      studies in albino mice were carried out using maximal electroshock seizure (MES)
      test and strychnine induced seizure (SIS) pattern test and results were compared
      with marketed formulation. RESULTS: The EE of the formulations varied from 84.37%
      to 98.11%. The ZP and PI values of the prepared batches were in the range of
      +23.46 to +28.07 and 0.256 and 0.365, respectively. Microscopic observation
      clearly indicated the stability of the emulsions during the storage period. All
      batches exhibited controlled in vitro drug release up to 12 hrs. Batch C11
      exhibited significantly longer duration of protection of seizure in mice against
      MES and exhibited comparable efficacy in SIS as compared to the marketed
      formulation. MAJOR CONCLUSION: Multiple emulsion of lamotrigine compared to the
      marketed tablet showed plasma drug concentration within therapeutic range for
      longer time and comparable efficacy.

PMID- 22615650
TI  - Effects of temperature and additives on stability and spectrum of a therapeutic
      fibroblast growth factor.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Human fibroblast growth factor 20
      (FGF20) is a 16.5 kDa protein containing 154 amino acid residues with reportedly
      poor thermal stability, and low stability, which are considered to be major
      factors that can limit its pharmacological applications. Thus, the aim of this
      study was to enhance the thermal stability and bio activity of a therapeutic
      FGF20 by addition of sucrose or heparin as additives and also at different
      temperatures. METHODS: A variety of biophysical techniques such as far-UV
      circular dichroism (CD), fluorescence and high resolution derivative UV
      absorption spectroscopy, were employed to characterize FGF20 and study the
      effects of heparin and sucrose on its thermal stability and bio activity at pH
      7.0. RESULTS: Results of this study suggest that human FGF20 is significantly
      unstable and induction of heat by increased temperatures results in aggregation
      and precipitation at pH 7.0. Great changes in the fluorescence intensity and
      shape were achieved by addition of heparin and sucrose at different temperatures
      compared to the control. From 10  degrees C to 60  degrees C, no significant
      changes were observed in far-UV CD spectrum compared to the control, but
      significant changes were observed by adding sucrose when these temperatures are
      above 45  degrees C. Upon addition of heparin and sucrose, the mitogenic activity
      increased significantly at all tested temperatures, and these changes may be
      related to the roles of heparin and sucrose on the structure and conformation of
      FGF20. CONCLUSION: Results of this study suggest that heparin and sucrose as
      additives seems to benjm sufficient to prevent thermal inactivation of FGF20 and
      also maintain its conformation stability and bio activity.

PMID- 22615651
TI  - Proliferation inhibition, cell cycle arrest and apoptosis induced in HL-60 cells
      by a natural diterpene ester from Daphne mucronata.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Gnidilatimonoein (Gn), a new diterpene
      ester from Daphne mucronata, possesses strong anti-metastasis and anti-tumor
      activities. In this study, its apoptosis and differentiation capabilities were
      evaluated by using the leukemia HL-60 cell line. MATERIAL AND METHODS: Cell
      prolifaration inhibition was estimated by MTT assay. The occurrence of apoptosis
      was evaluated by EtBr/AO double staining technique, cell cycle analyses and
      detection of apoptotic cells by Annexin V-FITC and propodium iodide (PI).
      Differentiation of the cells was determined by NBT reduction assay and the
      expression of specific cell surface markers such as CD14 and CD11b, were analyzed
      by flow cytometry. RESULTS: The drug decreased the growth of the cells dose- and
      time-dependently and the IC(50) was found to be 1.3 uM. Our data suggested that
      Gn induced both monocytic differentiation and apoptosis among HL-60 cells. In
      addition, cell cycle analyses showed an increase in G1 phase population by 24
      hrs, which was gradually replaced by Sub-G1 cell population (apoptotic cells) by
      72 hrs. CONCLUSION: Based on these data, the Gn-treated HL-60 cells displayed
      differentiation-dependent apoptosis. Thus, Gn might be a good candidate for
      differentiation therapy of leukemia, pending full biological evaluation of the
      compound among the wide array of leukemia cells.

PMID- 22615652
TI  - Clinical efficacy and safety of polyethylene glycol 3350 versus liquid paraffin
      in the treatment of pediatric functional constipation.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Functional constipation is prevalent in
      children. Recently polyethylene glycol has been introduced as an effective and
      safe drug to treat chronic constipation. There are only a few clinical trials on
      comparison of PEG and liquid paraffin in childhood constipation. The purpose of
      this study was to evaluate clinical efficacy and safety of PEG 3350 solution and
      liquid paraffin in the treatment of children with functional constipation in Sari
      Toba clinic during the period of 2008-2009. METHODS: Children with a history of
      functional constipation were subjects of this study. One hundred and sixty
      children of 2-12 years old with functional constipation were randomized in two
      PEG and paraffin treatment groups. Patients received either 1.0-1.5 g/kg/day PEG
      3350 or 1.0-1.5 ml/kg/day liquid paraffin for 4 months. Clinical efficacy was
      evaluated by stool and encopresis frequency/week and overall treatment success
      rate was compared in two groups. RESULTS AND MAJOR CONCLUSION: Compared with the
      baseline, defecation frequency/ week increased significantly and encopresis
      frequency meaningfully decreased in two groups during the period of the study.
      Patients using PEG 3350 had more success rate (mean: 95.3%+/-3.7) compared with
      the patients in paraffin group (mean: 87.2%+/-7.1) (p=0.087). Administration of
      PEG 3350 were associated with less adverse events than liquid paraffin. In
      conclusion in treatment of pediatric functional constipation, regarding clinical
      efficacy and safety, PEG 3350 were at least as effective as liquid paraffin and
      but less adverse drug events.

PMID- 22615653
TI  - Recombinant human erythropoietin reduces plasminogen activator inhibitor and
      ameliorates pro-inflammatory responses following trauma.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: sBesides its hematopoietic effects,
      erythropoietin (EPO) by mobilization of iron and modulation of some inflammatory
      cytokines has antioxidant and anti-inflammatory properties. The purpose of this
      study was to evaluate these effects of erythropoietin and its impact on organ
      function in traumatized patients. METHODS: Twenty-six ICU-admitted traumatized
      patients within 24 hrs after trauma were randomly assigned to the EPO (received
      EPO, 300 units/Kg/day) and Control (not received EPO) groups. The inflammatory
      biomarkers including Tumor Necrosis Factor alpha (TNF-alpha), Interleukin 1 (IL
      1), Plasminogen Activator Inhibitor 1 (PAI-1) and Nitrotyrosine were recorded at
      the admission, 3, 6 and 9 days thereafter. Acute Physiology and Chronic Health
      Evaluation (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores were
      also recorded. RESULTS: Among 12 patients (EPO group) TNF-alpha level at the day
      of 9 (P=0.046), and within EPO group at the days of 3 (P=0.026 ameliorate), 6
      (P=0.016), and 9 (P=0.052) were significantly lowered. Level of IL-1 and PAI-1
      decreased significantly at days of 3, 6 and 9 post intervention. Also there were
      significant differences between two groups in the SOFA score during three
      measured time intervals (the first, third and seventh days). CONCLUSION: From the
      results of this study it seems that injection of erythrocyte stimulating agent is
      well tolerated and inhibits the inflammatory response and oxidative stress
      following trauma.

PMID- 22615654
TI  - Effects of training in the Morris water maze on the spatial learning acquisition
      and VAChT expression in male rats.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: It has been well established that
      cholinergic pathway plays an important role in learning and memory processes. The
      present study was designed to evaluate the effects of Morris water maze (MWM)
      training on spatial memory acquisition and expression of the vesicular
      acetylcholine transporter (VAChT) in male rats. METHODS: In this study, training
      trials of all groups of animals were conducted in the MWM task. Rats received one
      training session consisting of four trials per day which continued for another
      four consecutive days. Controls received visible platform MWM training. The
      escape latency, the traveled distance and swimming speed for each rat were
      recorded and used to evaluate the performance of the animal during training
      period. For evaluation of expression of VAChT protein levels, brain tissues from
      animals in each experiment were obtained immediately after the last trial on the
      related experimental day and processed for immunohistochemistry staining and
      western blotting analysis. RESULTS: There was a significant difference between
      animals subjected to one day training and those receiving four days of training
      in escape latency and travel distance. There were an apparent increase in VAChT
      immunoreactivity in the medial septal area (MSA) and CA1 region of the
      hippocampus in one day and four day trained animals compared with controls
      (visible group). Quantitative immunostaining analysis by optical density
      measurements in the CA1 region and evaluation of immunopositive neurons in medial
      septal area of brain sections confirmed qualitative findings. Assessment of VAChT
      protein level expression in hippocampus by western blotting evaluation showed the
      same pattern of immunohistochemistry results. CONCLUSION: Overall, results of
      this study reveal changes in cholinergic neuron activity in different stages of
      training in the MWM task. Data suggest that there is a significant level of
      cholinergic neuronal activity during early stages of the training especially in
      the hippocampus region that may contribute to the apparent increase in VAChT
      expression.

PMID- 22615655
TI  - A review on phytochemistry and medicinal properties of the genus Achillea.
AB  - Achillea L. (Compositae or Asteraceae) is a widely distributed medicinal plant
      throughout the world and has been used since ancient time. Popular indications of
      the several species of this genus include treatment of wounds, bleedings,
      headache, inflammation, pains, spasmodic diseases, flatulence and dyspepsia.
      Phytochemical investigations of Achillea species have revealed that many
      components from this genus are highly bioactive. There are many reports on the
      mentioned folk and traditional effects. Although, the medicinal properties of
      Achillea plants are recognized worldwide, there are only one review article
      mainly about the structures of the phytochemical constituents of Achillea. The
      present paper reviews the medicinal properties of various species of Achillea,
      which have been examined on the basis of the scientific in vitro, in vivo or
      clinical evaluations. Various effects of these plants may be due to the presence
      of a broad range of secondary active metabolites such as flavonoids, phenolic
      acids, coumarins, terpenoids (monoterpenes, sesquiterpenes, diterpenes,
      triterpenes) and sterols which have been frequently reported from Achillea
      species.

PMID- 22615656
TI  - Direct Technetium radiopharmaceuticals production using a 30MeV Cyclotron.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Technetium-99m is the major radionuclide
      used in the world and mainly is provided by fission product. However extensive
      research has been conducted on the use of accelerators for production of (99m)Tc.
      This investigation reports the production of (99m)Tc radioisotope using
      cyclotrons and the preparation, quality control and biodistribution studies of
      four major Tc-radiopharmaceuticals. METHODS: The high purity molybdenum natural
      target (130 mg/cm(2)) was irradiated in a Cyclone 30 accelerator using 160 uA of
      25 MeV proton beam energy for 1000 uA-h. After dissolution, the technetium
      radionuclides were extracted using methyl ethyl ketone (MEK) followed by
      preparation of Tc-MIBI, Tc-DTPA, Tc-DMSA and Tc-phytate as radiopharmaceutical
      samples. RESULTS: The results of quality controls and animal biodistribution
      studies showed successful production of Tc radionuclides (including (99m)Tc) in
      the bombarded target and subsequent labelling of the kit with Tc. CONCLUSION: The
      developed high power Mo target if constructed using enriched (100)Mo, could be a
      practical method for large-scale production of (99m)Tc and promising as an
      alternative to fission product (99)Mo-(99m)Tc generators for local applications
      near cyclotron facilities.

PMID- 22615657
TI  - Preparation and evaluation of sustained release microballoons of propranolol.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: The purpose of the present investigation
      was to characterize, optimize and evaluate microballoons of Propranolol
      hydrochloride and to increase its boioavailability by increasing the retention
      time of the drug in the gastrointestinal tract. METHODS: Propranolol
      hydrochloride-loaded microballoons were prepared by the non-aqueous O/O emulsion
      solvent diffusion evaporation method using Eudragit RSPO as polymer. It was found
      that preparation temperature determined the formation of cavity inside the
      microballoon and this in turn determined the buoyancy. Microballoons were
      subjected to particle size determination, micromeritic properties, buoyancy,
      entrapment efficiency, drug loading, in vitro drug release and IR study. The
      correlation between the buoyancy, bulk density and porosity of microballoons were
      elucidated. The release rate was determined in simulated gastric fluid (SGF) of
      pH 1.2 at 37+/-0.5 degrees C. RESULTS: The microballoons presented spherical and
      smooth morphologies (SEM) and were porous due to presence of hollow cavity.
      Microballoons remained buoyant for >12 hrs for the optimized formulation. The
      formulation demonstrated favorable in vitro floating and release characteristics.
      The encapsulation efficiency was high. In vitro dissolution kinetics followed the
      Higuchi model. The drug release from microballoons was mainly controlled by
      diffusion and showed a biphasic pattern with an initial burst release, followed
      by sustained release for 12 hrs. The amount of the drug which released up to 12
      hrs was 82.05+/-0.64%. Statistical analysis (ANOVA) showed significant difference
      (p<0.05) in the cumulative amount of drug released after 30 min, and up to 12 hrs
      from optimized formulations. CONCLUSION: The designed system for propanolol would
      possibly be advantageous in terms of increased bioavailability and patient
      compliance.

PMID- 22615658
TI  - Sustained-release effervescent floating matrix tablets of baclofen: development,
      optimization and in vitro-in vivo evaluation in healthy human volunteers.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Baclofen, a centrally acting skeletal
      muscle relaxant, is indicated in the long-term treatment of spasticity. It is
      difficult to formulate baclofen sustained release dosage forms because its
      absorption on arrival to colon (or even before) is low or nonexistent. In the
      present investigation efforts were made to improve the bioavailability of
      baclofen by increasing the residence time of the drug through sustained-release
      matrix tablet formulation via gastroretentive mechanism. METHODS: Tablets were
      prepared by wet granulation technique. The influence of gas generating and gel
      forming agents, amount of baclofen and total weight of tablet on physical
      properties, in vitro buoyancy, floating lag time, drug release, DSC, X-ray
      studies were investigated. The release mechanisms were explored and explained by
      applying zero order, first order, Higuchi and Korsmeyer equations. The selected
      formulations were subjected to stability study for the period of three months.
      RESULTS: For all formulations, kinetics of drug release from tablet followed
      Higuchi's square root of time kinetic treatment heralding diffusion as
      predominant mechanism of drug release. Formulations containing 20 mg and 40 mg (F
      1 and F-7) showed similar release profiles. There was no significant change in
      the selected formulations, when subjected to accelerated stability conditions
      over a period of three months. X-ray imaging in six healthy human volunteers
      revealed a mean gastric retention period of 5.50+/-0.7 hrs for the selected
      formulation. CONCLUSION: Stable, sustained release effervescent floating matrix
      tablets of baclofen could be prepared by wet granulation technique.

PMID- 22615660
TI  - Population pharmacokinetics of oral high-dose busulfan in adult patients
      undergoing hematopoietic stem cell transplantation.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Many factors have been reported that
      contribute to the wide intra- and inter-patient variability of Busulfan (Bu)
      disposition. The purpose of this study was to develop a population
      pharmacokinetic model and to determine the covariates affecting the
      pharmacokinetics (PK) of Bu in Iranian adult patients who received oral high-dose
      as a conditioning regimen before Hematopoietic Stem Cell Transplantation (HSCT).
      METHODS: A population PK analysis was performed in 30 patients who received an
      oral Bu and cyclophosphamide regimen before HSCT. Bu was given orally according
      to the protocol of the institution. In order to prevent seizures caused by Bu,
      phenytoin was administered orally one hour before each dose of Bu.A total of 180
      blood samples were analyzed by HPLC and PK parameters were estimated by the non
      linear mixed effect model by MONOLIX 3.1 program. A one-compartment model with an
      additive error model was used to describe the concentration-time profile of Bu.
      RESULTS: Patients' disease and weight was found to be the determinant factors for
      clearance (CL) and the volume of distribution (Vd) according to Monolix analysis.
      The covariate entered in final model followed by these equations:[Formula: see
      text][Formula: see text] In this limited study, the age (15-43 years) had no
      significant effect. For a patient weighting 60 kg, the typical CL and Vd were
      estimated to be 13.4 l/hr and 42.6 L, respectively. The interindividual
      variability of CL and Vd were 13.6 and 6.3%, respectively. There was no
      significant metabolic induction in these four days as is evident by comparing the
      trough levels of Bu. However it should be mentioned that, one tailed t-test p
      values of the days of two and three, two and four and three and four were 0.083,
      0.069 and 0.388, respectively. MAJOR CONCLUSIONS: Results of this study showed
      that the type of disease was a determinant of CL and the weight of patient was a
      determinant of Vd for Bu population PK parameters. A reliable PK parameters and
      Css, estimated from only one plasma concentrations (5 hrs after the first dose),
      were validated. Since these methods require few sampling and are easy to be used,
      the limited sampling methods might be advantageous in the routine clinical
      practice.

PMID- 22615659
TI  - Pharmacokinetics of dl-praeruptorin A after single-dose intravenous
      administration to rats with liver cirrhosis.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: As a novel drug in the treatment of
      cardiac diseases, dl-praeruptorin A (Pd-Ia) is the major active component of
      traditional herbal medicine Peucedanum praeruptorum Dunn and is metabolized
      primarily via cytochrome P450 isozymes (CYP) 3A1 and 3A2 in rats. In the present
      study, the influence of liver cirrhosis on pharmacokinetics of Pd-Ia and hepatic
      mRNA expression of CYP3A1 and 3A2 in rats with experimental liver cirrhosis (LC
      rats) were evaluated. METHODS: Pd-Ia was given intravenously (5 mg kg(-1)) to LC
      rats induced by dimethylnitrosamine and pharmacokinetic variables were measured.
      Enzyme kinetic metabolism of Pd-Ia in rat hepatic microsomes was also
      investigated and hepatic mRNA expression of CYP3A1 and 3A2 were measured by real
      time PCR. RESULTS AND MAJOR CONCLUSION: After intravenous administration in LC
      rats, the area under the plasma concentration-time curve from time zero to
      infinity (AUC0-8) was significantly greater than that in control rats, which
      might be due to slower rate of the hepatic blood flow and significant slower
      hepatic intrinsic clearance (CL(int)) in rats. The decreased metabolic clearance
      of Pd-Ia in LC rats might be at least partly caused by the decreased levels of
      CYP3A1 and 3A2 responsible for Pd-Ia metabolism. These findings may provide new
      insights into the inter- and intra-individual pharmacokinetic variability of Pd
      Ia.

PMID- 22615661
TI  - In vivo bioavailability studies of sumatriptan succinate buccal tablets.
AB  - BACK GROUND AND THE PURPOSE OF STUDY:  Sumatriptan succinate is a Serotonin 5-
      HT1 receptor agonist, used in treatment of migraine. It is absorbed rapidly but
      incompletely when given orally and undergoes first-pass metabolism, resulting in
      a low absolute bioavailability of about 15%. The aim of this work was to design
      mucoadhesive bilayered buccal tablets of sumatriptan succinate to improve its
      bioavailability. METHODS: Mucoadhesive polymers carbopol 934 (Carbopol), HPMC
      K4M, HPMC K15M along with ethyl cellulose as an impermeable backing layer were
      used for the preparation of mucoadhesive bilayered tablets. In vivo
      bioavailability studies was also conducted in rabbits for optimized formulation
      using oral solution of sumatriptan succinate as standard. RESULTS: Bilayered
      buccal tablets (BBT) containing the mixture of Carbopol and HPMC K4M in the ratio
      1:1 (T1) had the maximum percentage of in vitro drug release within 6 hrs. The
      optimized formulation (T1) followed non-Fickian release mechanism. The percentage
      relative bioavailability of sumatriptan succinate from selected bilayered buccal
      tablets (T1) was found to be 140.78%. CONCLUSIONS: Bilayered buccal tablets of
      sumatriptan succinate was successfully prepared with improved bioavailability.

PMID- 22615662
TI  - A comparison of the effects of reboxetine and placebo on reaction time in adults
      with Attention Deficit-Hyperactivity Disorder (ADHD).
AB  - OBJECTIVE: Some studies have demonstrated that Reaction Time (RT) is longer in
      patients with ADHD which in turn may be associated with educational and
      occupational impairment and increased driving risks. Any alteration on RT which
      is induced by the treatment in this population may have great consequences
      positively or negatively. This study was designed to examine the effects of
      reboxetine on RT in adults with Attention Deficit-Hyperactivity Disorder (ADHD).
      METHODS: A total of 30 adult patients with ADHD who did not suffer from any other
      major psychiatric disorder were eligible to participate in this double blind,
      placebo controlled study. Patients were randomly assigned to receive either
      reboxetine (4 mg/day for one week, then 8 mg/day) or placebo for 4 weeks. RT was
      assessed at baseline and after 4 weeks by validated software which collects and
      analyses the data for auditory and visual stimulants. Numbers of correct
      responses, omission and substitution errors for each stimulus were calculated.
      RESULTS: Regarding visual tasks and in comparison with baseline scores, the
      number of correct responses increased significantly and the number of omission
      errors decreased significantly after 4 weeks of treatment (P<0.05) in both
      groups. However, with regard to auditory tasks scores, no significant differences
      were found at the end of the study compared to the baseline in each of the two
      groups. Additionally, no significant differences were noted between the two
      groups when both visual and auditory tasks were considered. CONCLUSION: Results
      of this study showed that reboxetine did not affect the RT of the patients when
      both visual and auditory tasks were assessed. Further studies with larger number
      of patients and for a longer period of time are required to confirm the result of
      this study.

PMID- 22615663
TI  - Suppression of humoral immune response to hepatitis B surface antigen vaccine in
      BALB/c mice by 1-methyl-tryptophan co-administration.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Indoleamine 2,3-dioxygenase (IDO)
      suppresses adaptive immune response. The purpose of this study was to determine
      the effect of the IDO inhibitor namely 1-methyl-DL-tryptophan (DL-1-MT) on
      antibody production after vaccination with hepatitis B surface (HBs) antigen.
      METHODS: Four groups of BALB/c mice were immunized with a HBs antigen vaccine. In
      the first group the vaccine had no DL-1-MT, whereas in the other three groups the
      vaccine contained 1 mg, 10 mg and 20 mg DL-1-MT. Blood samples were collected 5
      weeks post-vaccination and anti-HBs antibodies in the serum were measured by
      ELISA. RESULTS: Compared to the three groups of mice that were immunized with the
      vaccines containing DL-1-MT, serum anti-HBs level was much higher in the mice
      that were immunized with the vaccine with out DL-1-MT. CONCLUSIONS: Inhibition of
      IDO at the time of vaccination decreased humoral immune response to HBs antigen
      vaccine. The idea that IDO activity is simply immunosuppressive may need to be re
      evaluated.

PMID- 22615664
TI  - Efficacy and safety of Iranian made Deferasirox (Osveral(r)) in Iranian major
      thalassemic patients with transfusional iron overload: A one year prospective
      multicentric open-label non-comparative study.
AB  - PURPOSE OF THE STUDY: to determine the efficacy, adverse effects and safety of a
      new Iranian generic product of deferasirox (Osveral(r)) in Iranian transfusion
      dependent major thalassemic (TD-MT) patients. METHODS: In 9 main thalassemia
      treatment centers, all of TD-MT patients (aged >=2 yrs) with serum ferritin (SF)
      levels>=1000 ng/ml, or >100 ml/kg of RBC transfusion,who could not tolerate
      parental iron chelating were recruited regardless of their previous iron
      chelation therapy. Periodical clinical and laboratory evaluations were conducted
      for adverse effects (AEs). Primary efficacy end point was Mean of Relative Change
      of Serum Ferritin (MRC-SF) from the baseline level during one year. Analysis of
      variance (ANOVA), t test, chi-square or Fisher exact test were used for statistic
      analysis appropriately (P values <0.05 were considered as statistical
      significant). RESULTS: In 407 cases the male/female ratio was 0.98. Mean age was
      11.5+/-7.4 (2-58) years. The mean of initiating dose of Osveral(r) and mean usage
      dose during the study was 23.5+/-4.9 mg/kg and 24.9+/-4.9 mg/kg respectively. MRC
      SF was -11.44% +/-38.92 and it showed significant decline in SF (P value<0.001)
      one hundred and forty eight patients out of 407 patients experienced at least
      one. AE, the most common of them were transient increase in serum creatinin
      (97;24.1%) and>5 time increase in transaminases (24;5.89%).The causes of
      discontinuation of treatment were non-satisfactory treatment ( 24; 5.8%), poor or
      non-compliance of patients (21;5.1%), and adverse effects (13; 3.1%) CONCLUSION:
      A detailed comparison with similar studies on deferasirox (Exjade(r)) shows a
      promising efficacy and safety for its Iranian generic product (Osveral (r)).

PMID- 22615665
TI  - Formulation and evaluation of olanzapine matrix pellets for controlled release.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Olanzapine is an antipsychotic used in
      treatment of schizophrenia. This research was carried out to design oral
      controlled release matrix pellets of water insoluble drug Olanzapine (OZ), using
      blend of Sodium Alginate (SA) and Glyceryl Palmito-Stearate (GPS) as matrix
      polymers, micro crystalline cellulose (MCC) as spheronizer enhancer and Sodium
      Lauryl Sulphate (SLS) as pore forming agent. METHODS: OZ formulations were
      developed by the pelletization technique by drug loaded pellets and characterized
      with regard to the drug content, size distribution, Scanning Electron Microscopy
      (SEM), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared
      Spectroscopy (FTIR) and X-ray Diffraction study (XRD). Stability studies were
      carried out on the optimized formulation for a period of 90 days at 40+/-2 
      degrees C and 75+/-5% relative humidity. RESULTS AND MAJOR CONCLUSION: The drug
      content was in the range of 93.34-98.12%. The mean particle size of the drug
      loaded pellets was in the range 1024 to 1087um. SEM photographs and calculated
      sphericity factor confirmed that the prepared formulations were spherical in
      nature. The compatibility between drug and polymers in the drug loaded pellets
      was confirmed by DSC and FTIR studies. Stability studies indicated that pellets
      are stable. XRD patterns revealed the crystalline nature of the pure OZ. Loose
      surface crystal study indicated that crystalline OZ is present in all
      formulations and more clear in formulation F5. Drug release was controlled for
      more than 24 hrs and mechanism of the drug release followed by Fickian diffusion.
      It may be concluded that F5 is an ideal formulation for once a day
      administration.

PMID- 22615667
TI  - Effect of pomegranate pretreatment on the oral bioavailability of buspirone in
      male albino rabbits.
AB  - BACK GROUND AND THE PURPOSE OF STUDY: Many drug substances and variety of
      naturally occurring dietary or herbal components are capable of interaction with
      the CYP enzyme system. The aim of the study was to investigate the effect of
      pomegranate juice pretreatment on the bioavailability of buspirone in rabbits.
      METHODS: White New Zealand rabbits weighing 2.1+/-0.13 Kg were selected for
      study. The bioavailability of buspirone after pre-treatment with pomegranate
      juice (10 ml Kg(-1) for seven days) was compared with an oral solution of 10 mg
      kg(-1) of buspirone in distilled water. Animals were allowed free access to food
      and water, until night prior to dosing and were fasted for 10 hrs. In the first
      phase oral solution (10 mg kg(-1)) was administered through feeding tube followed
      by rinsing with 10 ml of water. In the second phase, the group was pretreated
      with pomegranate juice for 7 days and study was conducted after 15 days of
      washout period. RESULTS AND CONCLUSION: The results showed that there was a
      significant (p<0.05) difference in the bioavailability of buspirone after pre
      treatment with pomegranate juice.This increase in bioavailability might be due to
      inhibition of CYP3A4. Further studies are required to prove this mechanism in
      humans.

PMID- 22615666
TI  - Core shell methyl methacrylate chitosan nanoparticles: In vitro mucoadhesion and
      complement activation.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Studies show that chitosan nanoparticles
      increase mucoadhesivity and penetration of large molecules across mucosal
      surface. The aim of the present study was to investigate the use of thiolated
      chitosan in the development of polysaccharide-coated nanoparticles in order to
      confer specific functionality to the system. METHODS: Methyl methacrylate
      nanoparticles were coated with thiolated chitosan using a radical polymerization
      method. Thiolation was carried out using glutathione (GSH) to improve
      mucoadhesivity and permeation enhancing properties of chitosan. Mucoadhesion
      studies were carried out by calculating the amount of mucin adsorbed on
      nanoparticles in a specific period of time. Complement consumption was assessed
      in human serum (HS) by measurement of the hemolytic capacity of the complement
      system after contact with nanoparticles. RESULTS: The FT-IR and (1)HNMR spectra
      both confirmed the synthesis and showed the conjugation of thiolated chitosan to
      methyl methacrylate (MMA) homopolymer. Nanoparticles were spherical having a mean
      diameter within the range of about 334-650 nm and their positive zeta potential
      values indicated the presence of the cationic polysaccharide at the nanoparticle
      surface. Increasing the amount of thiolated chitosan led to mucoadhesivity and
      complement activation. However there was not dose dependent correlation between
      these phenomenons and the absence of thiolated chitosan led to particles with
      larger size, and without ability to activate complement process. MAJOR
      CONCLUSION: It can be concluded that nanoparticles could be used for the mucosal
      delivery of peptides and proteins. Results show that the thiolated chitosan had
      higher mucoadhesion and complement activation than unmodified chitosan.

PMID- 22615668
TI  - Cheap and easy modification of glassy carbon electrode for voltammetric
      determination of dopamine in the presence of ascorbic acid.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Different methods have been proposed to
      modify glassy carbon electrode in order to determine dopamine (DA), as one of the
      most important neurotransmitters in central nervous systems of mammalian. These
      methods are time comsuming and in some cases expensive. In this work, a very
      simple and cheap pretreatment method is developed for the bare glassy carbon
      electrode (GCE) to determine DA in the presence of Ascorbic acid (AA). METHODS:
      Cyclic voltammetry as an electrochemical activation procedure was used for
      activation of glassy carbon electrode in order to separate diffrential pulse
      peaks of DA and AA. The effect of different parameters such as pH for supporting
      electrolyte, range of potential and the number of cycles were investigated.
      Finally, differential pulse voltammetry was used to determine DA in the presence
      of AA. RESULTS: On the activated electrode under optimum condition, anodic peak
      of AA shifted to negative potentials and peak current decreased, but the peak
      current of DA increased. The peak current was linearly proportional to the bulk
      concentration of DA in the range of 6.5*10(-7)-1.8*10(-5) mol l(-1). The limit of
      detection was 6.2*10(-7) mol l(-1). CONCLUSION: A simple and cheap method was
      developed for the activation of glassy carbon electrode. It was possible to
      determine DA in the presence of AA on the treated electrode. The proposed method
      was used to determine DA in pharmacutical samples.

PMID- 22615669
TI  - Gastroprotective activity of alpha-terpineol in two experimental models of
      gastric ulcer in rats.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Several plant essential oils, as well as
      terpenes present in essential oils, have shown gastroprotective activity. The aim
      of the present work was to evaluate the gastroprotective activity of alpha
      terpineol, a monoterpene alcohol which is present in essential oils of various
      plants. METHODS: The gastroprotective activity of alpha-terpineol was evaluated
      in rats by assessing the changes in ethanol and indomethacin-induced gastric
      ulcer scores and on gastric secretory volume and total acidity in pylorus-ligated
      rats. Alpha-terpineol was administrated orally at the doses of 10, 30, and 50
      mg/kg one hour before administration of the ulcer inducing agents by the pylorus
      ligation procedure. The involvement of endogenous prostaglandins in the
      protective effect of alpha-terpineol in ethanol-induced gastric lesions test was
      assessed by administration of indomethacin (10 mg/kg, s.c.) 30 min before oral
      administration of alpha-terpineol at the dose of 50 mg/kg. RESULTS: alpha
      terpineol presented gastroprotective activity against ethanol-induced ulcers at
      the doses of 10, 30, and 50 mg/kg. Epoxy-carvone at the dose of 10 mg/kg did not
      present gastroprotective activity against ulcer induced by indomethacin, but at
      the doses of 30 and 50 mg/kg it attenuated the gastric damages induced by this
      agent significantly. Pretreatment with indomethacin did not prevent the
      gastroprotective effect of alpha-terpineol on ethanol-induced ulcers. Alpha
      terpineol also did not affect the gastric secretion in pylorus-ligated rats.
      MAJOR CONCLUSION: The results suggest that alpha-terpineol presents
      gastroprotective action which does not involve either an increase in the
      synthesis of endogenous prostaglandin or a decrease in the gastric acid
      secretion.

PMID- 22615670
TI  - Protective effect of pretreatment with thymoquinone against Aflatoxin B(1)
      induced liver toxicity in mice.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Thymoquinone (TQ) is one of the active
      components of Nigella sativa. The plant has been used in herbal medicine for
      treatment of many diseases including liver complications. The present study aimed
      to investigate protective effects of TQ on Aflatoxin B(1) (AFB(1)) induced liver
      toxicity in mice. METHODS: Animals were divided into six groups and treated
      intraperitoneally. Group 1 (blank) served as vehicle, group 2 (positive control)
      received AFB(1), Group 3 was treated with 9 mg/kg of TQ, Groups 4, 5 and 6 were
      treated with 4.5, 9 and 18 mg/kg of TQ, respectively. After three consecutive
      days, except for groups 1 and 3, animals were administered with a single dose of
      AFB(1) (2 mg/kg). All the animals were killed 24 hrs following the AFB(1)
      administration under ether anesthesia. Biochemical parameters including AST, ALT
      and ALP in serum samples and glutathione (GSH) and malondialdehyde (MDA) contents
      in liver homogenates were determined. Liver sections were collected for
      histopathological examination. RESULTS: Findings of this study showed that AST,
      ALT, ALP and MDA levels were significantly lower in the TQ treated animals as
      compared to AFB(1) group (group 2). Furthermore, TQ was able to recover
      glutathione content (GSH) of liver tissue. The best response, however, was
      observed with the dose of 9 mg/kg. Liver sections of AFB(1) intoxicated mice
      showed inflammation, necrosis, hyperplasia of kupffer and infiltration of
      mononuclear cells, dilation of sinusoids and disruption of hepatocytes, while
      treatment with TQ helped to normalize liver architecture in accordance to
      biochemical findings. CONCLUSION: Taken collectively, TQ has a protective role
      with optimum dose of 9 mg/kg in AFB(1) hepatotoxicity.

PMID- 22615671
TI  - The effect of Frankincense in the treatment of moderate plaque-induced
      gingivitis: a double blinded randomized clinical trial.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Extract of Boswellia Serrata species has
      been used in the Indian traditional medicine in the treatment of various
      inflammatory diseases. The present study was designed to evaluate anti
      inflammatory effects of Frankincense in the treatment of gingivitis, which is a
      periodontal tissue inflammatory disease. METHODS: This double blind randomized
      placebo controlled trial was carried out among high school female students with
      moderate plaque-induced gingivitis. Based on either administration of 0.1 gram of
      Frankincense extract or 0.2 gram of its powder or placebo and whether the
      patients undergone scaling and root planning (SRP) or not, they were randomly
      assigned to 6 groups. The primary efficacy outcome was changes in Gingival Index
      (Loe & Sillness) and the secondary outcomes were alteration in plaque index
      (Sillness & Loe), bleeding index (Cowell) and probing pocket depth (WHO probe).
      All indices were measured in the 0, 7th and 14th days of the study. RESULTS:
      Seventy five patients ranged of 15-18 years old were enrolled. At the end of the
      study, the indices in all groups showed significant decreases in comparison to
      the first day (p< 0.05), except for the bleeding index in the group without SRP
      and drug therapy (p=0.111). More precise analysis of data revealed that SRP in
      association with Frankincense application (either extract or powder) can lead to
      remarkable decrease in inflammatory indices in comparison to the groups without
      SRP and drug therapy (p<0.001). In addition, no significant difference was
      observed between powder or extract therapy (p >0.05) and between patients
      received either SRP or treatment alone (p=0.169). CONCLUSION: Frankincense, a
      safe and low-cost herbal medicine, may be feasibly applied to improve
      inflammation based disease of gingival as an adjunct to the conventional
      mechanical therapy.

PMID- 22615672
TI  - Protective effects of aqueous and ethanolic extracts of Nigella sativa L. and
      Portulaca oleracea L. on free radical induced hemolysis of RBCs.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: It has been shown that Nigella sativa L.
      and Portulaca oleracea L. have many antioxidant components. In the present study,
      the cytoprotective effect of ethanolic and aqueous extracts of N.sativa and
      P.oleracea against hemolytic damages induced by free radical initiator, AAPH [2,
      2' azobis (2- amidinopropane) hydrochloride] was evaluated. METHODS: Hemolysis
      was induced by addition of AAPH. To study the cytoprotective effect, aqueous (50,
      200, 300, 400, 800 ug/ml) and ethanolic (25, 100, 150, 200 and 400 ug/ml)
      extracts of N. sativa and aqueous (25, 50, 100, 150, 200 and 400 ug/ml) and
      ethanolic (300, 600, 900, 1200 and 1800 ug/ml) extracts of P. oleracea were
      employed. RBCs were incubated with both extracts and AAPH at 37  degrees C for 6
      hrs. In order to evaluate the impact of the time of addition, extracts were added
      one and 2 hrs after AAPH. Samples of suspensions were removed at different times
      and the degree of hemolysis was assessed spectrophotometrically by reading the
      absorption of supernatants at 540 nm. RESULTS: Aqueous (300, 400 and 800 ug/ml)
      and ethanolic (150, 200 and 400 ug/ml) extracts of N.sativa and also, aqueous
      (100, 150, 200 and 400 ug/ml) and ethanolic (1200, 1800 ug/ml) extracts of
      P.oleracea showed concentration-dependent cytoprotective effects. Addition of
      extracts one hour after AAPH reduced but did not eliminate protective activities
      of extracts. CONCLUSION: Cytorotective effect of aqueous and ethanolic extracts
      of N. sativa and P. oleracea against AAPH- induced hemolysis may be related to
      antioxidant properties of these plants.

PMID- 22615673
TI  - Screening of the anticonvulsant activity of some plants from Fabaceae family in
      experimental seizure models in mice.
AB  - BACKGROUND AND PURPOSE OF THE STUDY: Fabaceae is the third largest family of
      flowering plants. Lack of essential oils in the plants of this family can be an
      advantage in search for safe and effective medicines. In this study the
      anticonvulsant effect of the leaves of Albizzia julibrissin, Acacia juliflora,
      Acacia nubica and aerial parts of Astragalus obtusifolius was evaluated in
      pentylenetetrazole (PTZ) and maximal electroshock (MES) seizure tests. METHODS:
      The hydroalcoholic extracts of the plants were obtained by percolation. Different
      doses of the extracts were injected to the mice intraperitoneally (i.p.) and
      occurrence of clonic seizures induced by PTZ (60 mg/kg, i.p.) or tonic seizures
      induced by MES (50 mA, 50Hz, 1sec) were monitored up to 30 min after
      administration. Acute toxicity of the extracts was also assessed. The safe and
      effective extract was then fractionated by dichloromethane and anticonvulsant
      activity of the fractions was determined. Finally, the constituents of the
      extract and the fractions were screened by thin layer chromatography. RESULTS:
      Among the extracts, only A. obtusifolius extract showed low toxicity and
      protective effect against clonic seizures with ED50 value of 3.97 g/kg.
      Fractionation of the extract led to increase in anticonvulsant activity and ED50
      value of 2.86 g/kg was obtained for the aqueous fraction. Phytochemical screening
      revealed the presence of alkaloids, flavonoids, anthrones and saponins in the
      aqueous fraction. MAJOR CONCLUSION: The presence of anticonvulsant compounds in
      A. obtusifolius suggests further activity-guided fractionation and analytical
      studies to find out the potential of this plant as a source of anticonvulsant
      agent.

PMID- 22615674
TI  - Pentoxifylline decreases allodynia and hyperalgesia in a rat model of neuropathic
      pain.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Pentoxifylline (PTX) is a non-specific
      cytokite pain in several animal models and humans. However, long-term therapeutic
      effects of PTX on neuropathic pain in a rat model of chronic constriction injury
      (CCI) are not completely clear. This study was conducted to examine the effect of
      long-term administration of PTX on neuropathic pain in rats. METHODS: Neuropathic
      pain was induced by sciatic nerve ligation using of CCI model in rats. Rats were
      randomly assigned into sham, CCI-saline treated, and CCI-PTX treated (30 or 60
      mg/kg ip) groups. PTX or saline administered at 30 min before CCI and daily for
      14 days post-CCI. At the days of 3, 7, 11 and 14 following CCI, by using standard
      methods effects of thermal hyperalgesia, thermal and mechanical allodynia in all
      groups were examined using the standard methods. RESULTS: The CCI-saline treated
      group showed a significant increase in mechanical and thermal allodynia, and
      thermal hyperalgesia as compared with the sham group in the tested days.
      Administration of the higher dose of PTX (60 mg/kg/day), but not the lower dose
      (30 mg/kg/day) significantly reduced mechanical and thermal allodynia, as
      compared with the CCI-saline treated group on days of 3, 7, 11 and 14 (all P
      values<0.001). Also, both doses of PTX significantly reduced thermal hyperalgesia
      as compared with the CCI-saline treated group on these days (all P values<0.001).
      CONCLUSION: Results of this study show that chronic administration of PTX reduces
      the neuropathic pain in a rat model of CCI. Thus, this drug may have a
      therapeutic application in the treatment and management of neuropathic pain in
      humans.

PMID- 22615675
TI  - A systematic review on pharmacokinetic changes in critically ill patients: role
      of extracorporeal membrane oxygenation.
AB  - OBJECTIVE: Several factors including disease condition and different procedures
      could alter pharmacokinetic profile of drugs in critically ill patients. For
      optimizing patient's outcome, changing in dosing regimen is necessary.
      Extracorporeal Membrane Oxygenation (ECMO) is one of the procedures which could
      change pharmacokinetic parameters.The aim of this review was to evaluate the
      effect of ECMO support on pharmacokinetic parameters and subsequently
      pharmacotherapy. METHOD: A systematic review was conducted by reviewing all
      papers found by searching following key words; extracorporeal membrane
      oxygenation, ECMO, pharmacokinetic and pharmacotherapy in bibliography database.
      RESULTS: Different drug classes have been studied; mostly antibiotics. Almost all
      of the studies have been performed in neonates (as a case series). ECMO support
      is associated with altered pharmacokinetic parameters that may result in acute
      changes in plasma concentrations with potentially unpredictable pharmacological
      effect. Altreation in volume of distribution, protein binding, renal or hepatic
      clearance and sequestration of drugs by ECMO circuit may result in higher or
      lower doses requirement during ECMO. As yet, definite dosing guideline is not
      available. ECMO is extensively used recently for therapy and as a procedure
      affects pharmacokinetics profile along with other factors in critically ill
      patients. For optimizing the pharmacodynamic response and outcome of patients,
      drug regimen should be individualized through therapeutic drug monitoring
      whenever possible.

PMID- 22615676
TI  - Renoprotective effects of combining ACE inhibitors and statins in experimental
      diabetic rats.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: The combination of angiotensin II
      receptor antagonists and HMG CoA reductase inhibitors have shown to confer
      renoprotection.The purpose of this study was to find out the renoprotective
      effects of telmisartan and atorvastatin in combination and in monotherapy of
      Streptozotocin (STZ) induced diabetic nephropathy in rats. METHODS: Diabetes was
      induced by i.p injection of STZ to rats, after 18 hrs of fasting. Diabetic rats
      were randomly grouped and treated with telmisartan and atorvastatin in
      combination as well as monotherapy for 30 days. The serum and urine glucose,
      creatinine and serum triglyceride, cholesterol, albumin and micro-albumin and
      blood urea nitrogen, total protein and histological analyses of the left kidney
      were performed at the end of the study. RESULTS: By the end of the study, the
      combination showed significant (P < 0.05) improvement in urine glucose, serum
      cholesterol, serum and urine creatinine, blood urea nitrogen, total protein,
      serum albumin, micro-albuminuria levels in comparison to monotherapy. However,
      this combination didn't show significant changes on serum glucose and
      triglyceride levels. Kidney pathological injury was attenuated by the combination
      as compared to the diabetic group. CONCLUSION: The present study document that,
      telmisartan and atorvastatin combination have better renoprotective effects but
      not with individual drug when compared to the diabetic group. The combination
      also attenuated the progression of diabetic nephropathy by slowing the
      proteinuria and microalbuminuria and these effects were confirmed by
      histopathological analysis.

PMID- 22615677
TI  - Effects of polygonum aviculare herbal extract on proliferation and apoptotic gene
      expression of MCF-7.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: One of the most common malignancies in
      women is breast cancer. Although several treatments for breast cancer are
      available, application of herbal medicine as a supplementary treatment is a new
      option to help curing the disease. In this study anticancer effects of Polygonum
      avicular herbal extract was investigated. METHODS: Polygonum avicular extract was
      obtained by methanol. MCF-7 cell line was treated with different concentrations
      of Polygonum avicular (50, 100, 150, 200, 250, 300,350 400 ng/ul) for different
      time lengths ( 6, 12, 24, and 48 hrs). MTT assay and Flow Cytometry were used to
      evaluate cell proliferation and apoptosis, respectively. RT-PCR was also carried
      out to evaluate the expression of apoptotic genes. RESULTS AND DISCUSSION:
      Results showed that Polygonum avicular induced cytotoxicity in MCF-7 cell line at
      concentrations higher than 300 ng/ul and this was confirmed by the highest rate
      of cell death as measured by Trypan Blue and MTT assays. RT-PCR results showed up
      regulation of P53 and down-regulation of Bcl-2 proteins which implied the ability
      of Polygonum avicular to induce apoptosis in MCF-7 cells and confirmed its
      anticancer property. Further studies are required to evaluate effects of the
      extract on other apoptotic genes.

PMID- 22615678
TI  - The presence of amorpha-4, 11-diene synthase, a key enzyme in artemisinin
      production in ten Artemisia species.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Artemisinin is one of the most effective
      medicine against malaria, which is produced naturally by Artemisia annua in low
      yield. It is produced in a metabolic pathway, in which several genes and gene
      products are involved. One of the key genes in this pathway is am1, which encodes
      amorpha-4, 11-diene synthase (ADS), a key enzyme in artemisinin biosynthesis
      pathway. The aim of this study was to determine the presence of this gene in ten
      Artemisia species in order to increase the yield of production of Artemisinin.
      METHODS: The experiments were carried out using PCR. Specific primers were
      designed based on the published am1 gene sequence obtained from A. annua (NCBI,
      accession number AF327527). RESULTS: The amplification of this gene by the
      specific primers was considered as a positive sign for the potentiality of
      artemisinin production. Since the entire am1 gene was not amplified in any of the
      10 species used, four parts of the gene, essential in ADS enzyme function,
      corresponding to a) pair site of Arg10-Pro12 in the first 100 amino acids, b)
      aspartate rich motif (DDXXD), c) active site final lid and d) active site
      including farnesyl diphosphate (FDP) ionization sites and catalytic site in the
      ADS enzyme, were investigated. MAJOR CONCLUSION: The sequence corresponding to
      ADS active site was amplified only in A. annua, A. aucheri and A.
      chamaemelifolia. The negative results obtained with other species could be due to
      some sequence alteration, such as point mutations or INDELs. We propose A.
      aucheri and A. chamaemelifolia as two potential candidate species for further
      characterization, breeding and transferring am1 gene for artemisinin
      overproduction.

PMID- 22615679
TI  - 5-HT(1A) receptor activation improves anti-cataleptic effects of levodopa in 6
      hydroxydopamine-lesioned rats.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: In Parkinson>s disease (PD) prolong use
      of L-DOPA causes some motor disorders such as wearing-off and L-DOPA induced
      dyskinesia (LID). In this investigation the effect of 8-OHDAPT, as a 5-HT(1A)
      agonist on anti-cataleptic effect of L-DOPA in 6-hydroxydopamine (6-OHDA)
      lesioned male Wistar rats was investigated. METHODS: Catalepsy was induced by
      unilateral injection of 6-OHDA (8 ug/2ul/rat) into the central region of the SNc.
      After 3 weeks as a recovery period, animals received intraperitoneally (i.p.) L
      DOPA (15 mg/kg) twice daily for 20 days, and anti-cataleptic effect of L-DOPA was
      assessed by bar-test at days of 5, 10, 15 and 20. RESULTS AND MAJOR CONCLUSION:
      The results showed that L-DOPA had anti-cataleptic effect only until the day of
      15, and its effect was decreased on the day of 20. On the day of 21, rats were co
      injected with three different doses of 8-OHDAPT (0.1, 0.5 and 2.5 mg/kg, i.p.)
      and L-DOPA (15 mg/kg, ip). 8-Hydroxy-2-(di-n-propylamino) tetralin (8-OHDAPT)
      improved anti-cataleptic effect of L-DOPA at the dose of 0.5 mg/kg. Moreover the
      effect of 8-OHDAPT on anti-cataleptic effect of L-DOPA (15 mg/kg, ip) was
      abolished by 1-(2-methyoxyphenyl)-4-[4-(2-phthalamido) butyl] piperazine
      hydrobromide (NAN-190; 0.5 mg/kg, i.p.) as a 5-HT(1A) receptor antagonist.
      According to the obtained results, it may be concluded that activation of 5
      HT(1A) receptors by 8-OHDAPT may improve anti-cataleptic effect of L-DOPA in a 6
      OHDA- induced rat model of PD. Further studies are required to clarify the exact
      mechanism of interaction between 5-HT(1A) and dopaminergic neurons.

PMID- 22615681
TI  - Preparation and antifungal activity of spray-dried amphotericin B-loaded
      nanospheres.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Amphotericin B (AmB) which is an
      appropriate antibiotic for the treatment of mycosis has many toxic effects
      including nephrotoxicity. Recently preparation of a new drug loaded nanoparticles
      for the reduction of toxicity and increase in the effectiveness of AmB has been
      reported. The objective of this study was to prepare and evaluate in vitro and in
      vivo efficacy of the spray-dried AmB-loaded nanospheres. METHODS: AmB-loaded
      nanospheres was prepared by means of nanoprecipitation method. The spray-dried
      nanospheres was prepared by using aerosil and AmB entrapment efficacy was
      measured by HPLC method. Minimum inhibitory concentration (MIC) of AmB-loaded
      nanospheres against Candida albicans (ATCC 90028) was determined by using
      microdilution method and its in vitro haemolytic effect and antifungal efficacy
      on infected rabbits was also analyzed. RESULTS: The entrapment efficacy for AmB
      loaded nanospheres was 65.2%+/-3. The MIC of AmB-loaded nanospheres against C.
      albicans compared to the free antibiotic was lower significantly. Also, the AmB
      loaded nanospheres found to be 9.5 times less toxic than free AmB on human red
      blood cells. In vivo testing indicated that AmB-loaded nanospheres have a
      stronger protective effect against candidiasis compared to the free AmB.
      CONCLUSION: Results of this study suggest that prepared spray-dried AmB-loaded
      nanospheres would be a good choice for the treatment of mycosis because of low
      toxicity and high stability and effectiveness.

PMID- 22615680
TI  - Formulation and in vivo evaluation for anti-aging effects of an emulsion
      containing basil extract using non- invasive biophysical techniques.
AB  - BACKGROUND AND THE PURPOSE OF STUDY: Skin aging is a complex process induced by
      constant exposure to ultraviolet (UV) irradiation and damages human skin. UV
      generates reactive oxygen species leading to collagen deficiency and eventually
      skin wrinkling. Basil contains a number of phenolics and favonoids which possess
      antioxidant properties. The aim of this study was to formulate and investigate
      the antiaging potential of a cream containing Basil extract. METHODS: A single
      blinded study was conducted using non-invasive methods. Formulation containing 3%
      of the concentrated extract of Basil was developed by entrapping in the inner
      aqueous phase of w/o emulsion and base contained no extract. Both creams were
      stored at different storage conditions of 8 degrees C, 25 degrees C, 40 degrees C
      and 40 degrees C+ 75% relative humidity to predict their stabilities. The
      formulation and base were evaluated for their effects on various skin parameters
      i.e., moisture and trans epidermal water loss (TEWL), volume, energy and surface
      evaluation of the living skin (SELS). RESULTS: Significant effects (p<=0.05) were
      observed for both creams in the case of TEWL. The base showed insignificant
      (p<=0.05) while formulation showed significant effects on skin moisture. Volume,
      SELS SEr (skin roughness), SEsc (skin scaliness), SEsm (skin smoothness), SEw
      (skin wrinkles) parameter showed significant decline while texture parameter of
      'Energy' showed significant increase. CONCLUSION: The results statistically
      indicated that the active formulation containg extract of Basil exert antiaging
      effects when applied topically.

PMID- 22615682
TI  - Development of diclofenac sodium-loaded alginate-PVP K 30 microbeads using
      central composite design.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Diclofenac sodium is a non-steroidal
      anti-inflammatory agent with a short biological half-life (1-2 hr) and requires
      multiple dosing. This research was carried out to develop and optimize diclofenac
      sodium loaded alginate-PVP K 30 microbeads to eliminate the need for multiple
      dosing and adverse effects. METHODS: Diclofenac sodium loaded alginate-PVP K 30
      microbeads were prepared by ionotropic gelation. Particle size, drug release,
      swelling, FTIR and SEM analyses were performed. RESULTS: Optimized microbeads
      showed particle size of 0.589+/-0.054 to 0.620+/-0.067 mm, and drug entrapment
      efficiency of 97.88+/-2.86 to 98.60+/-3.55%. The in vitro drug release from
      microbeads was sustained over 10 hrs and followed controlled-release pattern.
      FTIR analysis indicated the possibility of intermolecular hydrogen bonding
      interactions, i.e., -OH...O=C in microbeads. CONCLUSION: Microbeads for oral
      controlled delivery of diclofenac sodium were successfully developed by
      ionotropic gelation.

PMID- 22615683
TI  - Preparation and comparison of chitosan nanoparticles with different degrees of
      glutathione thiolation.
AB  - BACKGROUND: Chitosan has gained considerable attentions as a biocompatible
      carrier to improve delivery of active agents. Application of this vehicle in the
      form of nanoparticle could profit advantages of nanotechnology to increase
      efficacy of active agents. The purpose of this study was to provide detailed
      information about chitosan-glutathione (Cht-GSH)nanoparticles which are gaining
      popularity because of their high mucoadhesive and extended drug release
      properties. METHODS: Depolymerization of chitosan was carried out using sodium
      nitrite method.Glutathione was covalently attached to chitosan and the solubility
      of the resulting conjugates was evaluated. Nanoparticles were prepared by ionic
      gelation method and then the effect of glutathione immobilization on properties
      of nanoparticles was investigated. RESULTS: Thiolation efficiency was higher in
      lower molecular weight chitosan polymers compared to unmodified chitosan
      nanoparticles. Cht-GSH conjugates of the same molecular weight but with different
      degrees of thiolation had the same hydrodynamic diameter (995+/- nm) and surface
      charge (102+/- mV) as unmodified chitosan, but comprised of a denser network
      structure and lower concentration. Cht-GSH nanoparticles also exhibited greater
      mucoadhesive strength which was less affected by ionic strength and pH of the
      environment. CONCLUSION: Thiolation improves the solubility of chitosan without
      any significant changes in size and charge of nanoparticles, but affects the
      nanogel structure.

PMID- 22615684
TI  - A QSAR study of some cyclobutenediones as CCR1 antagonists by artificial neural
      networks based on principal component analysis.
AB  - BACKGROUND AND PURPOSE OF THE STUDY: A quantitative structure activity
      relationship (QSAR) model based on artificial neural networks (ANN) was developed
      to study the activities of 29 derivatives of 3-amino-4-(2-(2-(4-benzylpiperazin-1
      yl)-2-oxoethoxy) phenylamino) cyclobutenedione as C-C chemokine receptor type
      1(CCR1) inhibitors. METHODS: A feed-forward ANN with error back-propagation
      learning algorithm was used for model building which was achieved by optimizing
      initial learning rate, learning momentum, epoch and the number of hidden neurons.
      RESULTS: Good results were obtained with a Root Mean Square Error (RMSE) and
      correlation coefficients (R(2)) of 0.189 and 0.906 for the training and 0.103 and
      0.932 prediction sets, respectively. CONCLUSION: The results reflect a nonlinear
      relationship between the Principal components obtained from calculated molecular
      descriptors and the inhibitory activities of the investigated molecules.

PMID- 22615685
TI  - Gephyrin, the enigmatic organizer at GABAergic synapses.
AB  - GABA(A) receptors are clustered at synaptic sites to achieve a high density of
      postsynaptic receptors opposite the input axonal terminals. This allows for an
      efficient propagation of GABA mediated signals, which mostly result in neuronal
      inhibition. A key organizer for inhibitory synaptic receptors is the 93 kDa
      protein gephyrin that forms oligomeric superstructures beneath the synaptic area.
      Gephyrin has long been known to be directly associated with glycine receptor beta
      subunits that mediate synaptic inhibition in the spinal cord. Recently, synaptic
      GABA(A) receptors have also been shown to directly interact with gephyrin and
      interaction sites have been identified and mapped within the intracellular loops
      of the GABA(A) receptor alpha1, alpha2, and alpha3 subunits. Gephyrin-binding to
      GABA(A) receptors seems to be at least one order of magnitude weaker than to
      glycine receptors (GlyRs) and most probably is regulated by phosphorylation.
      Gephyrin not only has a structural function at synaptic sites, but also plays a
      crucial role in synaptic dynamics and is a platform for multiple protein-protein
      interactions, bringing receptors, cytoskeletal proteins and downstream signaling
      proteins into close spatial proximity.

PMID- 22615686
TI  - Stimulus-evoked high frequency oscillations are present in neuronal networks on
      microelectrode arrays.
AB  - Pathological high frequency oscillations (250-600 Hz) are present in the brains
      of epileptic animals and humans. The etiology of these oscillations and how they
      contribute to the diseased state remains unclear. This work identifies the
      presence of microstimulation-evoked high frequency oscillations (250-400 Hz) in
      dissociated neuronal networks cultured on microelectrode arrays (MEAs).
      Oscillations are more apparent with higher stimulus voltages. As with in vivo
      studies, activity is isolated to a single electrode, however, the MEA provides
      improved spatial resolution with no spread of the oscillation to adjacent
      electrodes 200 MUm away. Oscillations develop across four weeks in vitro.
      Oscillations still occur in the presence of tetrodotoxin and synaptic blockers,
      and they cause no apparent disruption in the ability of oscillation-presenting
      electrodes to elicit directly evoked action potentials (dAPs) or promote the
      spread of synaptic activity throughout the culture. Chelating calcium with
      ethylene glycol tetraacetic acid (EGTA) causes a temporal prolongation of the
      oscillation. Finally, carbenoxolone significantly reduces or eliminates the high
      frequency oscillations. Gap junctions may play a significant role in maintaining
      the oscillation given the inhibitory effect of carbenoxolone, the propagating
      effect of reduced calcium conditions and the isolated nature of the activity as
      demonstrated in previous studies. This is the first demonstration of stimulus
      evoked high frequency oscillations in dissociated cultures. Unlike current models
      that rely on complex in vivo recording conditions, this work presents a simple
      controllable model in neuronal cultures on MEAs to further investigate how the
      oscillations occur at the molecular level and how they may contribute to the
      pathophysiology of disease.

PMID- 22615687
TI  - Mixed Electrical-Chemical Synapses in Adult Rat Hippocampus are Primarily
      Glutamatergic and Coupled by Connexin-36.
AB  - Dendrodendritic electrical signaling via gap junctions is now an accepted feature
      of neuronal communication in mammalian brain, whereas axodendritic and axosomatic
      gap junctions have rarely been described. We present ultrastructural,
      immunocytochemical, and dye-coupling evidence for "mixed" (electrical/chemical)
      synapses on both principal cells and interneurons in adult rat hippocampus. Thin
      section electron microscopic images of small gap junction-like appositions were
      found at mossy fiber (MF) terminals on thorny excrescences of CA3 pyramidal
      neurons (CA3pyr), apparently forming glutamatergic mixed synapses. Lucifer Yellow
      injected into weakly fixed CA3pyr was detected in MF axons that contacted four
      injected CA3pyr, supporting gap junction-mediated coupling between those two
      types of principal cells. Freeze-fracture replica immunogold labeling revealed
      diverse sizes and morphologies of connexin-36-containing gap junctions throughout
      hippocampus. Of 20 immunogold-labeled gap junctions, seven were large (328-1140
      connexons), three of which were consistent with electrical synapses between
      interneurons; but nine were at axon terminal synapses, three of which were
      immediately adjacent to distinctive glutamate receptor-containing postsynaptic
      densities, forming mixed glutamatergic synapses. Four others were adjacent to
      small clusters of immunogold-labeled 10-nm E-face intramembrane particles,
      apparently representing extrasynaptic glutamate receptor particles. Gap junctions
      also were on spines in stratum lucidum, stratum oriens, dentate gyrus, and hilus,
      on both interneurons and unidentified neurons. In addition, one putative
      GABAergic mixed synapse was found in thin-section images of a CA3pyr, but none
      were found by immunogold labeling, suggesting the rarity of GABAergic mixed
      synapses. Cx36-containing gap junctions throughout hippocampus suggest the
      possibility of reciprocal modulation of electrical and chemical signals in
      diverse hippocampal neurons.

PMID- 22615688
TI  - Brain electromagnetic activity and lightning: potentially congruent scale
      invariant quantitative properties.
AB  - The space-time characteristics of the axonal action potential are remarkably
      similar to the scaled equivalents of lightning. The energy and current densities
      from these transients within their respective volumes or cross-sectional areas
      are the same order of magnitude. Length-velocity ratios and temporal durations
      are nearly identical. There are similar chemical consequences such as the
      production of nitric oxide. Careful, quantitative examination of the
      characteristics of lightning may reveal analogous features of the action
      potential that could lead to a more accurate understanding of these powerful
      correlates of neurocognitive processes.

PMID- 22615689
TI  - Parietal lesions produce illusory conjunction errors in rats.
AB  - When several different objects are presented, visual objects are perceived
      correctly only if their features are identified and then bound together. Illusory
      conjunction errors result when an object is correctly identified but is combined
      incorrectly. The parietal cortex (PC) has been shown repeatedly to play an
      important role in feature binding. The present study builds on a series of recent
      studies that have made use of visual search paradigms to elucidate the neural
      system involved in feature binding. This experiment attempts to define the role
      the PC plays in binding the properties of a visual object that varies on the
      features of color and size in rats. Rats with PC lesions or control surgery were
      exposed to three blocks of 20 trials administered over a 1-week period, with each
      block containing 10-one feature and 10-two feature trials. The target object
      consisted of one color object (e.g., black and white) and one size object (e.g.,
      short and tall). Of the 10 one feature trials, five of the trials were tailored
      specifically for size discrimination and five for color discrimination. In the
      two-feature condition, the animal was required to locate the targeted object
      among four objects with two objects differing in size and two objects differing
      in color. The results showed that the PC lesioned compared to control rats had
      difficulty in learning the one and two features components of the task and the
      rats also performed more poorly on the one vs. two feature components of the
      task. Based on a subsequent error analysis for color and size, the results showed
      a significant increase in illusory conjunction errors for the PC lesioned rats
      relative to controls for color and relative to color discrimination, suggesting
      that the PC may support feature binding as it relates to color. There was an
      increase in illusory conjunctions errors for both the PC lesioned and control
      animals for size, but this appeared to be due to highly variable performance with
      size discrimination. Overall these results suggest that the PC rats display
      performance errors that appear to be consistent with the notion of illusory
      conjunction errors.

PMID- 22615690
TI  - Examining neural correlates of skill acquisition in a complex videogame training
      program.
AB  - Acquisition of complex skills is a universal feature of human behavior that has
      been conceptualized as a process that starts with intense resource dependency,
      requires effortful cognitive control, and ends in relative automaticity on the
      multi-faceted task. The present study examined the effects of different
      theoretically based training strategies on cortical recruitment during
      acquisition of complex video game skills. Seventy-five participants were
      recruited and assigned to one of three training groups: (1) Fixed Emphasis
      Training (FET), in which participants practiced the game, (2) Hybrid Variable
      Priority Training (HVT), in which participants practiced using a combination of
      part-task training and variable priority training, or (3) a Control group that
      received limited game play. After 30 h of training, game data indicated a
      significant advantage for the two training groups relative to the control group.
      The HVT group demonstrated enhanced benefits of training, as indexed by an
      improvement in overall game score and a reduction in cortical recruitment post
      training. Specifically, while both groups demonstrated a significant reduction of
      activation in attentional control areas, namely the right middle frontal gyrus,
      right superior frontal gyrus, and the ventral medial prefrontal cortex,
      participants in the control group continued to engage these areas post-training,
      suggesting a sustained reliance on attentional regions during challenging task
      demands. The HVT group showed a further reduction in neural resources post
      training compared to the FET group in these cognitive control regions, along with
      reduced activation in the motor and sensory cortices and the posteromedial
      cortex. Findings suggest that training, specifically one that emphasizes
      cognitive flexibility can reduce the attentional demands of a complex cognitive
      task, along with reduced reliance on the motor network.

PMID- 22615691
TI  - Meditation increases the depth of information processing and improves the
      allocation of attention in space.
AB  - During meditation, practitioners are required to center their attention on a
      specific object for extended periods of time. When their thoughts get diverted,
      they learn to quickly disengage from the distracter. We hypothesized that
      learning to respond to the dual demand of engaging attention on specific objects
      and disengaging quickly from distracters enhances the efficiency by which
      meditation practitioners can allocate attention. We tested this hypothesis in a
      global-to-local task while measuring electroencephalographic activity from a
      group of eight highly trained Buddhist monks and nuns and a group of eight age
      and education matched controls with no previous meditation experience.
      Specifically, we investigated the effect of attentional training on the global
      precedence effect, i.e., faster detection of targets on a global than on a local
      level. We expected to find a reduced global precedence effect in meditation
      practitioners but not in controls, reflecting that meditators can more quickly
      disengage their attention from the dominant global level. Analysis of reaction
      times confirmed this prediction. To investigate the underlying changes in brain
      activity and their time course, we analyzed event-related potentials. Meditators
      showed an enhanced ability to select the respective target level, as reflected by
      enhanced processing of target level information. In contrast with control group,
      which showed a local target selection effect only in the P1 and a global target
      selection effect in the P3 component, meditators showed effects of local
      information processing in the P1, N2, and P3 and of global processing for the N1,
      N2, and P3. Thus, meditators seem to display enhanced depth of processing. In
      addition, meditation altered the uptake of information such that meditators
      selected target level information earlier in the processing sequence than
      controls. In a longitudinal experiment, we could replicate the behavioral
      effects, suggesting that meditation modulates attention already after a 4-day
      meditation retreat. Together, these results suggest that practicing meditation
      enhances the speed with which attention can be allocated and relocated, thus
      increasing the depth of information processing and reducing response latency.

PMID- 22615692
TI  - Training-induced compensation versus magnification of individual differences in
      memory performance.
AB  - Do individuals with higher levels of task-relevant cognitive resources gain more
      from training, or do they gain less? For episodic memory, empirical evidence is
      mixed. Here, we revisit this issue by applying structural equation models for
      capturing individual differences in change to data from 108 participants aged 9
      12, 20-25, and 65-78 years. Participants learned and practiced an imagery-based
      mnemonic to encode and retrieve words by location cues. Initial mnemonic
      instructions reduced between-person differences in memory performance, whereas
      further practice after instruction magnified between-person differences. We
      conclude that strategy instruction compensates for inefficient processing among
      the initially less able. In contrast, continued practice magnifies ability-based
      between-person differences by uncovering individual differences in memory
      plasticity.

PMID- 22615693
TI  - Ventral and dorsal streams in the evolution of speech and language.
AB  - The brains of humans and old-world monkeys show a great deal of anatomical
      similarity. The auditory cortical system, for instance, is organized into a
      ventral and a dorsal pathway in both species. A fundamental question with regard
      to the evolution of speech and language (as well as music) is whether human and
      monkey brains show principal differences in their organization (e.g., new
      pathways appearing as a result of a single mutation), or whether species
      differences are of a more subtle, quantitative nature. There is little doubt
      about a similar role of the ventral auditory pathway in both humans and monkeys
      in the decoding of spectrally complex sounds, which some authors have referred to
      as auditory object recognition. This includes the decoding of speech sounds
      ("speech perception") and their ultimate linking to meaning in humans. The
      originally presumed role of the auditory dorsal pathway in spatial processing, by
      analogy to the visual dorsal pathway, has recently been conceptualized into a
      more general role in sensorimotor integration and control. Specifically for
      speech, the dorsal processing stream plays a role in speech production as well as
      categorization of phonemes during on-line processing of speech.

PMID- 22615694
TI  - Presumed idiopathic central serous chorioretinopathy in a 12-year-old girl.
AB  - Idiopathic central serous chorioretinopathy (CSC) typically affects middle-aged
      males. To date, only one case of idiopathic CSC in a prepubertal subject has been
      reported. Atypical idiopathic CSC presentation may be challenging to diagnose.
      Exclusion of secondary causes of serous retinal detachment (SRD) is warranted. We
      describe the atypical case of a 12-year-old female with a circumscribed SRD that
      resolved spontaneously and with fluorescein angiography (FA) findings that were
      compatible with idiopathic CSC. Optical coherence tomography (OCT) and systemic
      assessment were performed to exclude other etiologies. FA demonstrated multiple
      focal leaks in early phases, with subretinal leakage and pooling in late phases.
      OCT showed a localized circumscribed retinal detachment. Complete blood count was
      within normal limits. Serum cortisol was normal (22.1 MUg/dl) and mean arterial
      blood pressure was 100/60 mm Hg, thereby excluding secondary causes of CSC. This
      is the second reported case of idiopathic CSC in a prepubertal female and the
      first one documented by FA and OCT, as well as other studies to exclude secondary
      causes. Albeit rare, idiopathic CSC should be considered in the differential
      diagnosis of SRD in this (prepubertal) age group, after excluding secondary
      ocular or systemic etiologies.

PMID- 22615695
TI  - Intraretinal Exudates in Coats' Disease as Demonstrated by Spectral-Domain OCT.
AB  - PURPOSE: To describe the spectral-domain optical coherence tomography (SD-OCT)
      findings in a case of Coats' disease, with emphasis on the intraretinal exudates.
      METHODS: Case report of a 4.5-year-old girl who presented with total exudative
      retinal detachment and organized exudates in a stellate configuration. SD-OCT was
      performed before and after treatment, which included surgical drainage of
      subretinal fluid and indirect laser application during the surgery. RESULTS: At
      presentation, the SD-OCT showed an elevation of the foveal contour, with
      thickening of the retina, many exudates and a large quantity of subretinal fluid.
      Two months after the surgical treatment, SD-OCT revealed a significant reduction
      in the amount of subretinal fluids, but with persistence of the exudates.
      CONCLUSION: SD-OCT can be used as an important tool in order to describe the
      changes in each layer of the retina in Coats' disease. Considering the
      histopathological findings in Coats' disease, it is reasonable to assume that the
      exudates accumulate in the outer plexiform layer.

PMID- 22615696
TI  - Bilateral Implantation of Scleral-Fixated Cionni Endocapsular Rings and Toric
      Intraocular Lenses in a Pediatric Patient with Marfan's Syndrome.
AB  - The management of ectopia lentis in Marfan's syndrome is challenging. Multiple
      disease-associated factors conspire to deprive these patients of adequate vision.
      While optical correction with glasses and contact lenses is usually advocated
      early on, the irregular astigmatism and even partial aphakia that accompanies
      advanced cases generally warrant surgical intervention. Several surgical
      strategies have been devised to manage these challenging cases, including the
      combination of endocapsular or pars plana lensectomy and iris or scleral fixation
      of the intraocular lens (IOL) or IOL-bag complex. All of the reported cases have
      been implanted with IOLs that correct for myopia only. With toric lenses, it is
      now possible to correct for corneal astigmatism in these patients as well,
      provided that the capsular bag is maintained and can be properly centered. We
      report the combination of scleral-fixated Cionni endocapsular rings and toric
      IOLs in a pediatric patient with bilateral ectopia lentis secondary to Marfan's
      syndrome.

PMID- 22615697
TI  - Corneal melting two weeks after pterygium excision with topical mitomycin C:
      successfully treated with lamellar keratoplasty and amnion membrane
      transplantation.
AB  - PURPOSE: To report the management of a case of corneal melting two weeks after
      pterygium excision with intraoperative topical mitomycin C (MMC). METHODS: Case
      report. RESULTS: A 57-year-old male was referred to our Department for therapy of
      rapidly progressive corneal melting two weeks after primary pterygium surgery
      with MMC (0.2 mg/ml) in September 2009. Initial treatment consisted of topical
      and systemic immunosuppression along with topical antibiotics. Eight days after
      presentation, the patient underwent successful lamellar keratoplasty and amnion
      membrane transplantation. Subconjunctival injection of triamcinolone (40 mg/ml)
      and topical bevacizumab were used to manage the increased fibrovascular activity
      around the site of the former pterygium. CONCLUSION: Topical use of MMC during
      pterygium surgery may be related to serious postoperative complications such as
      progressive inflammatory corneal melting. The etiology may be multifactorial,
      which is related to MMC-induced inflammation and/or induced apoptosis. A
      therapeutic option is the described combination of systemic and local anti
      inflammatory treatment along with lamellar keratoplasty and amniotic membrane
      transplantation. Adjunctive therapy may be needed if recurrence occurs.

PMID- 22615698
TI  - Resolution of Persistent Cystoid Macular Edema due to Central Retinal Vein
      Occlusion in a Vitrectomized Eye following Intravitreal Implant of Dexamethasone
      0.7 mg.
AB  - We report the case of a 62-year-old woman with a history of vitreoretinal surgery
      for vitreous hemorrhage secondary to central retinal vein occlusion (CRVO).
      Because of the persistence of macular edema (ME), she received 2 intravitreal
      injections of bevacizumab 0.5 mg (Avastin(r), Genentech/Roche) three months after
      vitrectomy, without functional or anatomical improvement. Six months after
      vitrectomy, she therefore received an intravitreal implant of dexamethasone 0.7
      mg (Ozurdex(r)). An improvement in her best-corrected visual acuity and central
      macular thickness, as measured by optical coherence tomography, was detected 7
      days after the injection, and complete resolution of the ME and retinal
      hemorrhages was observed 6 months after the injection. Dexamethasone intravitreal
      implant might be an effective treatment option in ME secondary to CRVO, also in
      vitrectomized eyes.

PMID- 22615699
TI  - Bilateral Exudative Retinal Detachment in HELLP Syndrome.
AB  - The HELLP syndrome is a pregnancy complication, life-threatening for mother and
      child, characterized by hypertension, elevated liver enzymes and low platelets.
      Blurred vision is the most common visual complaint. A rare case of bilateral
      exudative retinal detachment associated with the HELLP syndrome is described in a
      30-year-old Caucasian woman at 33 weeks' gestation. The retinal detachment did
      reattach with good improvement in vision under steroid therapy. The case
      highlights the importance of early involvement of the ophthalmologist when
      pregnant women complain about visual disorders.

PMID- 22615700
TI  - Choroidal folds in acute-stage vogt-koyanagi-harada disease patients with
      relatively short axial length.
AB  - PURPOSE: To report 2 cases of Vogt-Koyanagi-Harada disease accompanied by
      remarkable choroidal folds in the acute stage. The early indicator of recurrence
      in these 2 cases was the identification of choroidal folds by spectral-domain
      optical coherence tomography (SD-OCT). CASE REPORTS: A 68-year-old woman (Case 1)
      presented with visual loss in both eyes. Funduscopic examination revealed optic
      disc swelling and serous retinal detachment in both eyes. SD-OCT revealed
      remarkable choroidal folds and serous retinal detachment. After the initiation of
      systemic steroid treatment, choroidal folds disappeared rapidly and the amount of
      serous retinal detachment reduced remarkably. Choroidal folds observed on SD-OCT
      were the early indicators of recurrence prior to the emergence of serous retinal
      detachment. A 62-year-old woman (Case 2) presented with bilateral blurred vision
      and metamorphopsia. SD-OCT showed remarkable choroidal folds and serous retinal
      detachment in both eyes. After the initiation of systemic steroid treatment,
      choroidal folds and serous retinal detachment disappeared. At the time of
      recurrence, choroidal folds were observed by OCT. DISCUSSION: During monitoring
      of Vogt-Koyanagi-Harada disease treatment, choroidal folds could be an early sign
      of recurrence. When choroidal folds are observed and recognized as an early
      indicator of recurrence, a prompt increase in steroids can improve the patients'
      prognosis. Finally, both cases presented here had relatively short axial lengths,
      and we speculate that a shortened axial length may be a cause of choroidal folds
      in the acute stage of the disease.

PMID- 22615701
TI  - BLAP-Tags, TUBEs and DUB-Chips: Combined Novel Technologies will Advance
      Molecular Epithelial Physiology.
AB  - The field of ubiquitylation and deubiquitylation of proteins in molecular
      physiology is growing at a rapid rate. Our understanding of molecular physiology
      of these processes may become limited by the advancement of technologies that
      scientists can employ. Therefore, it is important to approach physiological
      questions of ubiquitylation and deubiquitylation of proteins from a multiple
      methodological direction. Indeed, the role of ubiquitylation and deubiquitylation
      of proteins in cellular function has been implicated in the pathophysiology of
      human diseases including cancer, viral diseases, and neurodegenerative disorders.
      There are many modulators (activators and inhibitors) of ubiquitylation and
      deubiquitylation. Therefore, the link is being able to rapidly assess potential
      modulators of ubiquitylation and deubiquitylation and determine which specific
      modulators play a role(s) within a particular physiological setting. After the
      specific modulators have been identified, further experimentation is required to
      assess the downstream use as potential clinical targets for a particular disease.
      The first step is to identify the specific modulators. This perspective
      highlights a multi-prong technologies approach that uses three novel technologies
      (BLAP-tagged proteins, TUBES, and DUB-Chips) that can rapidly identify a number
      of potential candidates that modulate ubiquitylation and deubiquitylation of
      cellular proteins.

PMID- 22615703
TI  - Action mechanisms of transcranial direct current stimulation in Alzheimer's
      disease and memory loss.
AB  - The pharmacological treatment of Alzheimer's disease (AD) is often limited and
      accompanied by drug side effects. Thus alternative therapeutic strategies such as
      non-invasive brain stimulation are needed. Few studies have demonstrated that
      transcranial direct current stimulation (tDCS), a method of neuromodulation with
      consecutive robust excitability changes within the stimulated cortex area, is
      beneficial in AD. There is also evidence that tDCS enhances memory function in
      cognitive rehabilitation in depressive patients, Parkinson's disease, and stroke.
      tDCS improves working and visual recognition memory in humans and object
      recognition learning in the elderly. AD's neurobiological mechanisms comprise
      changes in neuronal activity and the cerebral blood flow (CBF) caused by altered
      microvasculature, synaptic dysregulation from beta-amyloid peptide accumulation,
      altered neuromodulation via degenerated modulatory amine transmitter systems,
      altered brain oscillations, and changes in network connectivity. tDCS alters (i)
      neuronal activity and (ii) human CBF, (iii) has synaptic and non-synaptic after
      effects (iv), can modify neurotransmitters polarity-dependently, (v) and alter
      oscillatory brain activity and (vi) functional connectivity patterns in the
      brain. It thus is reasonable to use tDCS as a therapeutic instrument in AD as it
      improves cognitive function in manner based on a disease mechanism. Moreover, it
      could prove valuable in other types of dementia. Future large-scale clinical and
      mechanism-oriented studies may enable us to identify its therapeutic validity in
      other types of demential disorders.

PMID- 22615704
TI  - Do the dynamics of prior information depend on task context? An analysis of
      optimal performance and an empirical test.
AB  - In speeded two-choice tasks, optimal performance is prescribed by the drift
      diffusion model. In this model, prior information or advance knowledge about the
      correct response can manifest itself as a shift in starting point or as a shift
      in drift rate criterion. These two mechanisms lead to qualitatively different
      choice behavior. Analyses of optimal performance (i.e., Bogacz et al., 2006;
      Hanks et al., 2011) have suggested that bias should manifest itself in starting
      point when difficulty is fixed over trials, whereas bias should (additionally)
      manifest itself in drift rate criterion when difficulty is variable over trials.
      In this article, we challenge the claim that a shift in drift criterion is
      necessary to perform optimally in a biased decision environment with variable
      stimulus difficulty. This paper consists of two parts. Firstly, we demonstrate
      that optimal behavior for biased decision problems is prescribed by a shift in
      starting point, irrespective of variability in stimulus difficulty. Secondly, we
      present empirical data which show that decision makers do not adopt different
      strategies when dealing with bias in conditions of fixed or variable across-trial
      stimulus difficulty. We also perform a test of specific influence for drift rate
      variability.

PMID- 22615702
TI  - Imaging-genetics in autism spectrum disorder: advances, translational impact, and
      future directions.
AB  - Autism Spectrum Disorder (ASD) refers to a group of heterogeneous
      neurodevelopmental disorders that are unified by impairments in reciprocal social
      communication and a pattern of inflexible behaviors. Recent genetic advances have
      resolved some of the complexity of the genetic architecture underlying ASD by
      identifying several genetic variants that contribute to the disorder. Different
      etiological pathways associated with ASD may converge through effects on common
      molecular mechanisms, such as synaptogenesis, neuronal motility, and axonal
      guidance. Recently, with more sophisticated techniques, neuroimaging, and
      neuropathological studies have provided some consistency of evidence that altered
      structure, activity, and connectivity within complex neural networks is present
      in ASD, compared to typically developing children. The imaging-genetics approach
      promises to help bridge the gap between genetic variation, resultant biological
      effects on the brain, and production of complex neuropsychiatric symptoms. Here,
      we review recent findings from the developing field of imaging-genetics applied
      to ASD. Studies to date have indicated that relevant risk genes are associated
      with alterations in circuits that mediate socio-emotional, visuo-spatial, and
      language processing. Longitudinal studies ideally focused on early development,
      in conjunction with investigation for gene-gene, and gene-environment
      interactions may move the promise of imaging-genetics in ASD closer to the
      clinical domain.

PMID- 22615705
TI  - Temporal adaptation to audiovisual asynchrony generalizes across different sound
      frequencies.
AB  - The human brain exhibits a highly adaptive ability to reduce natural asynchronies
      between visual and auditory signals. Even though this mechanism robustly
      modulates the subsequent perception of sounds and visual stimuli, it is still
      unclear how such a temporal realignment is attained. In the present study, we
      investigated whether or not temporal adaptation generalizes across different
      auditory frequencies. In a first exposure phase, participants adapted to a fixed
      220-ms audiovisual asynchrony or else to synchrony for 3 min. In a second phase,
      the participants performed simultaneity judgments (SJs) regarding pairs of
      audiovisual stimuli that were presented at different stimulus onset asynchronies
      (SOAs) and included either the same tone as in the exposure phase (a 250 Hz
      beep), another low-pitched beep (300 Hz), or a high-pitched beep (2500 Hz).
      Temporal realignment was always observed (when comparing SJ performance after
      exposure to asynchrony vs. synchrony), regardless of the frequency of the sound
      tested. This suggests that temporal recalibration influences the audiovisual
      perception of sounds in a frequency non-specific manner and may imply the
      participation of non-primary perceptual areas of the brain that are not
      constrained by certain physical features such as sound frequency.

PMID- 22615706
TI  - Selective rapid eye movement sleep deprivation affects cell size and number in
      kitten locus coeruleus.
AB  - Cells in the locus coeruleus (LC) constitute the sole source of norepinephrine
      (NE) in the brain and change their discharge rates according to vigilance state.
      In addition to its well established role in vigilance, NE affects synaptic
      plasticity in the postnatal critical period (CP) of development. One form of CP
      synaptic plasticity affected by NE results from monocular occlusion, which leads
      to physiological and cytoarchitectural alterations in central visual areas.
      Selective suppression of rapid eye movement sleep (REMS) in the CP kitten
      enhances the central effects of monocular occlusion. The mechanisms responsible
      for heightened cortical plasticity following REMS deprivation (REMSD) remain
      undetermined. One possible mediator of an increase in plasticity is continuous NE
      outflow, which presumably persists during extended periods of REMSD. Tyrosine
      hydroxylase (TH) is the rate-limiting enzyme in the synthesis of NE and serves as
      a marker for NE-producing cells. We selectively suppressed REMS in kittens for 1
      week during the CP. The number and size of LC cells expressing immunoreactivity
      to tyrosine hydroxylase (TH-ir) was assessed in age-matched REMS-deprived (RD)-,
      treatment-control (TXC)-, and home cage-reared (HCC) animals. Sleep amounts and
      slow wave activity (SWA) were also examined relative to baseline. Time spent in
      REMS during the study was lower in RD compared to TXC animals, and RD kittens
      increased SWA delta power in the latter half of the REMSD period. The estimated
      total number of TH-ir cells in LC was significantly lower in the RD than in the
      TXC kittens and numerically lower than in the HCC animals. The size of LC cells
      expressing TH-ir was greatest in the HCC group. HCC cells were significantly
      larger than TH-ir cells in the RD kittens. These data are consistent with
      presumed reduction in NE in forebrain areas, including visual cortex, caused by 1
      week of REMSD.

PMID- 22615708
TI  - Alkali therapy in patients with metabolic acidosis.

PMID- 22615709
TI  - The authors reply: alkali therapy in patients with metabolic acidosis.

PMID- 22615710
TI  - A case of clear cell adenocarcinoma arising from the urethral diverticulum:
      Utility of urinary cytology and immunohistochemistry.
AB  - Carcinomas rarely arise from the urethral diverticulum. In this report, we
      present a case of clear cell adenocarcinoma arising from the urethral
      diverticulum. A 42-year-old woman complained of bloody discharge and lower back
      pain. Imaging studies showed a tumor involving the region surrounding the urethra
      and cystourethroscopy showed papillary and villous tumors in the urethral
      diverticula. Cytology of the urine sediment showed papillary or spherical
      clusters of atypical cells, some of which had clear abundant cytoplasm and formed
      mirror ball-like clusters, suggesting adenocarcinoma. Although histological
      diagnosis was indeterminate by biopsy and transurethral resection (TUR) because
      of absence of stromal invasion, surgically resected specimen via cysturethrectomy
      revealed that the tumor was clear cell carcinoma. Urinary cytological findings
      and immunohistochemical analysis for CD15, Ki-67, and p53 might be useful for
      accurate diagnosis of clear cell adenocarcinoma that arises from the urethral
      diverticulum when sufficient materials are not available by biopsy and TUR.

PMID- 22615711
TI  - Diagnosis of pulmonary hydatid disease presenting with solid nodule and mimicking
      malignancy by fine needle aspiration cytology.

PMID- 22615712
TI  - Endoscopic ultrasound and endobronchial ultrasound-guided fine-needle aspiration
      of deep-seated lymphadenopathy: Analysis of 1338 cases.
AB  - BACKGROUND: We retrospectively studied 1338 samples of lymph nodes obtained by
      endoscopic and endobronchial ultrasound-guided fine needle aspiration biopsy (EUS
      and EBUS-FNAB) with an objective of characterizing the utility of this diagnostic
      modality in the assessment of deep-seated lymphadenopathy. The secondary aims
      were to establish the utility in the diagnosis of lymphoma and to determine the
      number of passes required to obtain adequate cellularity for flow cytometric
      analysis. MATERIALS AND METHODS: On-site assessment was performed by a
      cytopathologist using Diff-Quik (American Scientific Products, McGraw Park, IL)
      stain. In addition, Papanicolaou and immunohistochemical stains were performed
      and additional samples were sent for flow cytometric analyses (n = 145). The
      final cytologic diagnosis was correlated with surgical pathology diagnosis and/or
      clinical follow-up. In select cases, fluorescence in situ hybridization analysis
      with specific probes was performed on Diff-Quik smears. RESULTS: Both morphology
      as well as ancillary studies (flow cytometry or immunohistochemical stain and/or
      fluorescence in situ hybridization) show that EUS and EBUS-FNA are effective
      techniques to detect and stage intrathoracic and intra-abdominal tumors.
      Operating characteristics show that these are highly sensitive (89%) and specific
      (100%) techniques for the diagnosis of lymphoma. At least two passes provided an
      average of 5.66 million cells (range, 0.12-62.32 million) for lymphoma cases.
      CONCLUSIONS: EUS and EBUS-FNA are powerful modalities to stage malignancies and
      at least two passes can provide adequate cells for flow cytometric analysis. We
      also demonstrate that fluorescence in situ hybridization analysis can be
      performed on Diff-Quik-stained and mounted smears.

PMID- 22615707
TI  - Vaccine Development Against Leishmania donovani.
AB  - Visceral leishmaniasis (VL) caused by Leishmania donovani and Leishmania
      infantum/chagasi represents the second most challenging infectious disease
      worldwide, leading to nearly 500,000 new cases and 60,000 deaths annually.
      Zoonotic VL caused by L. infantum is a re-emergent canid zoonoses which
      represents a complex epidemiological cycle in the New world where domestic dogs
      serve as a reservoir host responsible for potentially fatal human infection and
      where dog culling is the only measure for reservoir control. Life-long immunity
      to VL has motivated development of prophylactic vaccines against the disease but
      very few have progressed beyond the experimental stage. No licensed vaccine is
      available till date against any form of leishmaniasis. High toxicity and
      increasing resistance to the current chemotherapeutic regimens have further
      complicated the situation in VL endemic regions of the world. Advances in
      vaccinology, including recombinant proteins, novel antigen-delivery
      systems/adjuvants, heterologous prime-boost regimens and strategies for
      intracellular antigen presentation, have contributed to recent advances in
      vaccine development against VL. Attempts to develop an effective vaccine for use
      in domestic dogs in areas of canine VL should be pursued for preventing human
      infection. Studies in animal models and human patients have revealed the
      pathogenic mechanisms of disease progression and features of protective immunity.
      This review will summarize the accumulated knowledge of pathogenesis, immune
      response, and prerequisites for protective immunity against human VL. Authors
      will discuss promising vaccine candidates, their developmental status and future
      prospects in a quest for rational vaccine development against the disease. In
      addition, several challenges such as safety issues, renewed and coordinated
      commitment to basic research, preclinical studies and trial design will be
      addressed to overcome the problems faced in developing prophylactic strategies
      for protection against this lethal infection.

PMID- 22615713
TI  - Depression and Anxiety Symptoms in Children and Adolescents with Autism Spectrum
      Disorders without Intellectual Disability.
AB  - Recent studies have shown that rates of depression and anxiety symptoms are
      elevated among individuals with autism spectrum disorders (ASDs) of various ages
      and IQs and that depression/anxiety symptoms are associated with higher IQ and
      fewer ASD symptoms. In this study which examined correlates of depression and
      anxiety symptoms in the full school-age range of children and adolescents (age 6
      18) with ASDs and IQs >= 70 (n=95), we also observed elevated rates of
      depression/anxiety symptoms, but we did not find higher IQ or fewer ASD symptoms
      among individuals with ASDs and depression or anxiety symptoms. These findings
      indicate an increased risk for depression/anxiety symptoms in children and
      adolescents with ASDs without intellectual disability, regardless of age, IQ, or
      ASD symptoms.

PMID- 22615715
TI  - The immune diet: meeting the metabolic demands of lymphocyte activation.
AB  - During the adaptive immune response, lymphocytes undergo dramatic changes in
      metabolism that accompany the proliferative burst and differentiation into
      functional subsets. This brief overview focuses on recent advances in
      understanding the mechanisms of this metabolic reprogramming in T lymphocytes.

PMID- 22615714
TI  - Applications of MicroRNAs in the Diagnosis and Prognosis of Lung Cancer.
AB  - INTRODUCTION: Lung cancer is the leading cause of cancer death worldwide, due to
      its late diagnosis and poor outcome. MicroRNAs (miRNAs) are small non-coding RNAs
      that regulate gene expression at the posttranscriptional levels by either
      degrading or blocking translation of messenger RNA targets. Accumulating evidence
      indicates that miRNAs play a pivotal role in the development and progression of
      human malignancies, including lung cancer.  AREAS COVERED: In this review, the
      authors focus on 1) application of miRNA-based biomarkers to help classify lung
      cancer, 2) application of the miRNA biomarkers for the early detection of lung
      cancer, and 3) use of miRNAs as biomarkers to predict outcomes of lung cancer. 
      EXPERT OPINION: MiRNAs provide promising biomarkers for the diagnosis and
      prognosis of lung cancer. The developed miRNA biomarkers should be
      comprehensively and prospectively validated in clinical trials before being used
      in laboratory settings.

PMID- 22615717
TI  - Minimally Invasive Periodontal Treatment Using the Er,Cr: YSGG Laser. A 2-year
      Retrospective Preliminary Clinical Study.
AB  - MINIMALLY INVASIVE SURGERY (MIS) USING THE ERBIUM, CHROMIUM: yttrium-scandium
      gallium-garnet (Er,Cr:YSGG) laser (Waterlase MD, Biolase, Irvine, CA) to treat
      moderate to advanced periodontal disease is presented as an alternative to
      conventional therapies. To date, there are few short- or long-term studies to
      demonstrate the effects of this laser in treating and maintaining periodontal
      health. Electronic clinical records from 16 patients - total of 126 teeth, with
      pocket depths ranging from 4 mm to 9 mm - were treated with the same protocol
      using the Er,Cr:YSGG laser. The mean baseline probing depths (PD) were 5 mm and
      clinical attachment levels (CAL) were 5 mm in the 4 - 6 mm pretreated laser
      group. The mean baseline probing depths were 7.5 and 7.6 mm for PD and CAL
      respectfully in the 7 - 9 mm pretreatment laser group. At the 2 year mark, the
      average PD was 3.2 +/- 1.1 mm for the 4-6 mm pocket group and the 7-9 mm pocket
      group had a mean PD of 3.7 +/- 1.2 mm. mean CAL was 3.1 +/- 1.1 mm for the 4-6 mm
      group and 3.6 +/- 1.2 for the 7-9 mm group with an overall reduction of 1.9 mm
      and 4.0 mm respectively. At one and two years, both groups remained stable with
      PD comparable to the three-month gains. The CAL measurements at one and two years
      were also comparable to the three-month gains.

PMID- 22615716
TI  - Development of feedstocks for cellulosic biofuels.
AB  - The inclusion of cellulosic ethanol in the Energy Independence and Security Act
      (EISA) of 2007 and the revised Renewable Fuel Standard (RFS2) has spurred
      development of the first commercial scale cellulosic ethanol biorefineries. These
      efforts have also revived interest in the development of dedicated energy crops
      selected for biomass productivity and for properties that facilitate conversion
      of biomass to liquid fuels. While many aspects of developing these feedstocks are
      compatible with current agricultural activities, improving biomass productivity
      may provide opportunities to expand the potential for biofuel production beyond
      the classical research objectives associated with improving traditional food and
      feed crops.

PMID- 22615718
TI  - Causes of adverse pregnancy outcomes and the role of maternal periodontal status 
      a review of the literature.
AB  - Preterm (PT) and Low birth weight (LBW) are considered to be the most relevant
      biological determinants of newborn infants survival, both in developed and in
      developing countries. Numerous risk factors for PT and LBW have been defined in
      the literature. Infections of the genitourinary tract infections along with
      various biological and genetic factors are considered to be the most common
      etiological factors for PT/LBW deliveries. However, evidence suggests that sub
      clinical infection sites that are also distant from the genitor-urinary tract may
      be an important cause for PT/LBW deliveries. Maternal periodontal status has also
      been reported by many authors as a possible risk factor for PT and LBW, though
      not all of the actual data support such hypothesis. The aim of this paper is to
      review the evidence from various published literature on the association between
      the maternal periodontal status and adverse pregnancy outcomes. Although this
      review found a consistent association between periodontitis and PT/LBW, this
      finding should be treated with great caution until the sources of heterogeneity
      can be explained.

PMID- 22615719
TI  - Rapid tooling method for soft customized removable oral appliances.
AB  - Traditionally oral appliances i.e. removable orthodontic appliances, bite splints
      and snoring / sleep apnea appliances are made with alginate impressions and wax
      registrations. Our aim was to describe the process of manufacturing customized
      oral appliances with a new technique i.e. rapid tooling method. The appliance
      should ideally be custom made to match the teeth. An orthodontic patient,
      scheduled for conventional orthodontic treatment, served as a study subject.
      After a precise clinical and radiographic examination, the approach was to
      digitize the patient's dental arches and then to correct them virtually by
      computer. Additive manufacturing was then used to fabricate a mould for a soft
      customized appliance. The mould was manufactured using stereolithography from
      Somos ProtoGen O-XT 18420 material. Casting material for the mould to obtain the
      final appliance was silicone. As a result we managed to create a customized soft
      orthodontic appliance. Also, the accuracy of the method was found to be adequate.
      Two versions of the described device were manufactured: one with small and one
      with moderate orthodontic force. The study person also gave information on the
      subjective patient adaptation aspects of the oral appliance.

PMID- 22615729
TI  - Using knowledge fusion to analyze avian influenza H5N1 in East and Southeast
      Asia.
AB  - Highly pathogenic avian influenza (HPAI) H5N1, a disease associated with high
      rates of mortality in infected human populations, poses a serious threat to
      public health in many parts of the world. This article reports findings from a
      study aimed at improving our understanding of the spatial pattern of the highly
      pathogenic avian influenza, H5N1, risk in East-Southeast Asia where the disease
      is both persistent and devastating. Though many disciplines have made important
      contributions to our understanding of H5N1, it remains a challenge to integrate
      knowledge from different disciplines. This study applies genetic analysis that
      identifies the evolution of the H5N1 virus in space and time, epidemiological
      analysis that determines socio-ecological factors associated with H5N1
      occurrence, and statistical analysis that identifies outbreak clusters, and then
      applies a methodology to formally integrate the findings of the three sets of
      methodologies. The present study is novel in two respects. First it makes the
      initiative attempt to use genetic sequences and space-time data to create a space
      time phylogenetic tree to estimate and map the virus' ability to spread. Second,
      by integrating the results we are able to generate insights into the space-time
      occurrence and spread of H5N1 that we believe have a higher level of
      corroboration than is possible when analysis is based on only one methodology.
      Our research identifies links between the occurrence of H5N1 by area and a set of
      socio-ecological factors including altitude, population density, poultry density,
      and the shortest path distances to inland water, coastlines, migrating routes,
      railways, and roads. This study seeks to lay a solid foundation for the
      interdisciplinary study of this and other influenza outbreaks. It will provide
      substantive information for containing H5N1 outbreaks.

PMID- 22615730
TI  - Proteomic validation of multifunctional molecules in mesenchymal stem cells
      derived from human bone marrow, umbilical cord blood and peripheral blood.
AB  - Mesenchymal stem cells (MSCs) are one of the most attractive therapeutic
      resources in clinical application owing to their multipotent capability, which
      means that cells can differentiate into various mesenchymal tissues such as bone,
      cartilage, fat, tendon, muscle and marrow stroma. Depending on the cellular
      source, MSCs exhibit different application potentials according to their
      different in vivo functions, despite similar phenotypic and cytological
      characteristics. To understand the different molecular conditions that govern the
      different application or differentiation potential of each MSC according to
      cellular source, we generated a proteome reference map of MSCs obtained from bone
      marrow (BM), umbilical cord blood (CB) and peripheral blood (PB). We identified
      approximately 30 differentially regulated (or expressed) proteins. Most up
      regulated proteins show a cytoskeletal and antioxidant or detoxification role
      according to their functional involvement. Additionally, these proteins are
      involved in the increase of cell viability, engraftment and migration in
      pathological conditions in vivo. In summary, we examined differentially expressed
      key regulatory factors of MSCs obtained from several cellular sources,
      demonstrated their differentially expressed proteome profiles and discussed their
      functional role in specific pathological conditions. With respect to the field of
      cell therapy, it may be particularly crucial to determine the most suitable cell
      sources according to target disease.

PMID- 22615731
TI  - Experience of pleasure and emotional expression in individuals with schizotypal
      personality features.
AB  - Difficulties in feeling pleasure and expressing emotions are one of the key
      features of schizophrenia spectrum conditions, and are significant contributors
      to constricted interpersonal interactions. The current study examined the
      experience of pleasure and emotional expression in college students who
      demonstrated high and low levels of schizotypal personality disorder (SPD) traits
      on self-report questionnaires. One hundred and seventeen subjects with SPD traits
      and 116 comparison controls were recruited to participate. Cluster analyses
      conducted in the SPD group identified negative SPD and positive SPD subgroups.
      The negative SPD group exhibited deficient emotional expression and anticipatory
      pleasure, but showed intact consummatory pleasure. The positive SPD group
      reported significantly greater levels of anticipatory, consummatory and total
      pleasure compared to the control group. Both SPD groups reported significantly
      more problems in everyday memory and greater levels of depressive and anxiety
      related symptoms.

PMID- 22615732
TI  - Deficiency in nucleotide excision repair family gene activity, especially ERCC3,
      is associated with non-pigmented hair fiber growth.
AB  - We conducted a microarray study to discover gene expression patterns associated
      with a lack of melanogenesis in non-pigmented hair follicles (HF) by microarray.
      Pigmented and non-pigmented HFs were collected and micro-dissected into the hair
      bulb (HB) and the upper hair sheaths (HS) including the bulge region. In
      comparison to pigmented HS and HBs, nucleotide excision repair (NER) family genes
      ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, ERCC6, XPA, NTPBP, HCNP, DDB2 and POLH
      exhibited statistically significantly lower expression in non- pigmented HS and
      HBs. Quantitative PCR verified microarray data and identified ERCC3 as highly
      differentially expressed. Immunohistochemistry confirmed ERCC3 expression in HF
      melanocytes. A reduction in ERCC3 by siRNA interference in human melanocytes in
      vitro reduced their tyrosinase production ability. Our results suggest that loss
      of NER gene function is associated with a loss of melanin production capacity.
      This may be due to reduced gene transcription and/or reduced DNA repair in
      melanocytes which may eventually lead to cell death. These results provide novel
      information with regard to melanogenesis and its regulation.

PMID- 22615733
TI  - Improving quality of care for maternal and newborn health: prospective pilot
      study of the WHO safe childbirth checklist program.
AB  - BACKGROUND: Most maternal deaths, intrapartum-related stillbirths, and newborn
      deaths in low income countries are preventable but simple, effective methods for
      improving safety in institutional births have not been devised. Checklist-based
      interventions aid management of complex or neglected tasks and have been shown to
      reduce harm in healthcare. We hypothesized that implementation of the WHO Safe
      Childbirth Checklist program, a novel childbirth safety program for institutional
      births incorporating a 29-item checklist, would increase delivery of essential
      childbirth practices linked with improved maternal and perinatal health outcomes.
      METHODS AND FINDINGS: A pilot, pre-post-intervention study was conducted in a sub
      district level birth center in Karnataka, India between July and December 2010.
      We prospectively observed health workers that attended to women and newborns
      during 499 consecutively enrolled birth events and compared these with observed
      practices during 795 consecutively enrolled birth events after the introduction
      of the WHO Safe Childbirth Checklist program. Twenty-nine essential practices
      that target the major causes of childbirth-related mortality, such as hand
      hygiene and uterotonic administration, were evaluated. The primary end point was
      the average rate of successful delivery of essential childbirth practices by
      health workers. Delivery of essential childbirth-related care practices at each
      birth event increased from an average of 10 of 29 practices at baseline (95%CI
      9.4, 10.1) to an average of 25 of 29 practices afterwards (95%CI 24.6, 25.3;
      p<0.001). There was significant improvement in the delivery of 28 out of 29
      individual practices. No adverse outcomes relating to the intervention occurred.
      Study limitations are the pre-post design, potential Hawthorne effect, and focus
      on processes of care versus health outcomes. CONCLUSIONS: Introduction of the WHO
      Safe Childbirth Checklist program markedly improved delivery of essential safety
      practices by health workers. Future study will determine if this program can be
      implemented at scale and improve health outcomes.

PMID- 22615734
TI  - The classical pink-eyed dilution mutation affects angiogenic responsiveness.
AB  - Angiogenesis is the process by which new blood vessels are formed from existing
      vessels. Mammalian populations, including humans and mice, harbor genetic
      variations that alter angiogenesis. Angiogenesis-regulating gene variants can
      result in increased susceptibility to multiple angiogenesis-dependent diseases in
      humans. Our efforts to dissect the complexity of the genetic diversity that
      regulates angiogenesis have used laboratory animals due to the availability of
      genome sequence for many species and the ability to perform high volume
      controlled breeding. Using the murine corneal micropocket assay, we have observed
      more than ten-fold difference in angiogenic responsiveness among various mouse
      strains. This degree of difference is observed with either bFGF or VEGF induced
      corneal neovascularization. Ongoing mapping studies have identified multiple loci
      that affect angiogenic responsiveness in several mouse models. In this study, we
      used F2 intercrosses between C57BL/6J and the 129 substrains 129P1/ReJ and
      129P3/J, as well as the SJL/J strain, where we have identified new QTLs that
      affect angiogenic responsiveness. In the case of AngFq5, on chromosome 7,
      congenic animals were used to confirm the existence of this locus and subcongenic
      animals, combined with a haplotype-based mapping approach that identified the
      pink-eyed dilution mutation as a candidate polymorphism to explain AngFq5. The
      ability of mutations in the pink-eyed dilution gene to affect angiogenic response
      was demonstrated using the p-J allele at the same locus. Using this allele, we
      demonstrate that pink-eyed dilution mutations in Oca2 can affect both bFGF and
      VEGF-induced corneal angiogenesis.

PMID- 22615735
TI  - BMP-2 up-regulates PTEN expression and induces apoptosis of pulmonary artery
      smooth muscle cells under hypoxia.
AB  - AIM: To investigate the role of bone morphogenetic protein 2 (BMP-2) in
      regulation of phosphatase and tensin homologue deleted on chromosome ten (PTEN)
      and apoptosis of pulmonary artery smooth muscle cells (PASMCs) under hypoxia.
      METHODS: Normal human PASMCs were cultured in growth medium (GM) and treated with
      BMP-2 from 5-80 ng/ml under hypoxia (5% CO(2)+94% N(2)+1% O(2)) for 72 hours.
      Gene expression of PTEN, AKT-1 and AKT-2 were determined by quantitative RT-PCR
      (QRT-PCR). Protein expression levels of PTEN, AKT and phosph-AKT (pAKT) were
      determined. Apoptosis of PASMCs were determined by measuring activities of
      caspases-3, -8 and -9. siRNA-smad-4, bpV(HOpic) (PTEN inhibitor) and GW9662
      (PPARgamma antagonist) were used to determine the signalling pathways. RESULTS:
      Proliferation of PASMCs showed dose dependence of BMP-2, the lowest proliferation
      rate was achieved at 60 ng/ml concentration under hypoxia (82.2+/-2.8%). BMP-2
      increased PTEN gene expression level, while AKT-1 and AKT-2 did not change.
      Consistently, the PTEN protein expression also showed dose dependence of BMP-2.
      AKT activity significantly reduced in BMP-2 treated PASMCs. Increased activities
      of caspase-3, -8 and -9 of PASMCs were found after cultured with BMP-2. PTEN
      expression remained unchanged when Smad-4 expression was inhibited by siRNA-Smad
      4. bpV(HOpic) and GW9662 (PPARgamma inhibitor) inhibited PTEN protein expression
      and recovered PASMCs proliferation rate. CONCLUSION: BMP-2 increased PTEN
      expression under hypoxia in a dose dependent pattern. BMP-2 reduced AKT activity
      and increased caspase activity of PASMCs under hypoxia. The increased PTEN
      expression may be mediated through PPARgamma signalling pathway, instead of
      BMP/Smad signalling pathway.

PMID- 22615736
TI  - The YARHG domain: an extracellular domain in search of a function.
AB  - We have identified a new bacterial protein domain that we hypothesise binds to
      peptidoglycan. This domain is called the YARHG domain after the most highly
      conserved sequence-segment. The domain is found in the extracellular space and is
      likely to be composed of four alpha-helices. The domain is found associated with
      protein kinase domains, suggesting it is associated with signalling in some
      bacteria. The domain is also found associated with three different families of
      peptidases. The large number of different domains that are found associated with
      YARHG suggests that it is a useful functional module that nature has recombined
      multiple times.

PMID- 22615737
TI  - Adherence to interferon beta-1b treatment in patients with multiple sclerosis in
      Spain.
AB  - BACKGROUND: Adherence to interferon beta-1b (INFbeta-1b) therapy is essential to
      maximize the beneficial effects of treatment in multiple sclerosis (MS). For that
      reason, the main objectives of this study are to assess adherence to INFbeta-1b
      in patients suffering from MS in Spain, and to identify the factors responsible
      for adherence in routine clinical practice. METHODOLOGY/PRINCIPAL FINDINGS: This
      was an observational, retrospective, cross-sectional study including 120 Spanish
      patients with MS under INFbeta-1b treatment. Therapeutic adherence was assessed
      with Morisky-Green test and with the percentage of doses received. The proportion
      of adherent patients assessed by Morisky-Green test was 68.3%, being indicative
      of poor adherence. Nevertheless, the percentage of doses received, which was
      based on the number of injected medication, was 94.3%. The main reason for
      missing INFbeta-1b injections was forgetting some of the administrations (64%).
      Therefore, interventions that diminish forgetfulness might have a positive effect
      in the proportion of adherent patients and in the percentage of doses received.
      In addition, age and comorbidities had a significant effect in the number of
      doses injected per month, and should be considered in the management of adherence
      in MS patients. CONCLUSION/SIGNIFICANCE: Among all the available methods for
      assessing adherence, the overall consumption of the intended dose has to be
      considered when addressing adherence.

PMID- 22615738
TI  - Herbal medicines for Parkinson's disease: a systematic review of randomized
      controlled trials.
AB  - OBJECTIVE: We conducted systematic review to evaluate current evidence of herbal
      medicines (HMs) for Parkinson's disease (PD). METHODS: Along with hand searches,
      relevant literatures were located from the electronic databases including
      CENTRAL, MEDLINE, EMBASE, CINAHL, AMED, PsycInfo, CNKI, 7 Korean Medical
      Databases and J-East until August, 2010 without language and publication status.
      Randomized controlled trials (RCTs), quasi-randomized controlled trials and
      randomized crossover trials, which evaluate HMs for idiopathic PD were selected
      for this review. Two independent authors extracted data from the relevant
      literatures and any disagreement was solved by discussion. RESULTS: From the 3432
      of relevant literatures, 64 were included. We failed to suggest overall estimates
      of treatment effects on PD because of the wide heterogeneity of used herbal
      recipes and study designs in the included studies. When compared with placebo,
      specific effects were not observed in favor of HMs definitely. Direct comparison
      with conventional drugs suggested that there was no evidence of better effect for
      HMs. Many studies compared combination therapy with single active drugs and
      combination therapy showed significant improvement in PD related outcomes and
      decrease in the dose of anti-Parkinson's drugs with low adverse events rate.
      CONCLUSION: Currently, there is no conclusive evidence about the effectiveness
      and efficacy of HMs on PD. For establishing clinical evidence of HMs on PD,
      rigorous RCTs with sufficient statistical power should be promoted in future.

PMID- 22615739
TI  - Evolution of cooperation driven by reputation-based migration.
AB  - How cooperation emerges and is stabilized has been a puzzling problem to
      biologists and sociologists since Darwin. One of the possible answers to this
      problem lies in the mobility patterns. These mobility patterns in previous works
      are either random-like or driven by payoff-related properties such as fitness,
      aspiration, or expectation. Here we address another force which drives us to move
      from place to place: reputation. To this end, we propose a reputation-based model
      to explore the effect of migration on cooperation in the contest of the
      prisoner's dilemma. In this model, individuals earn their reputation scores
      through previous cooperative behaviors. An individual tends to migrate to a new
      place if he has a neighborhood of low reputation. We show that cooperation is
      promoted for relatively large population density and not very large temptation to
      defect. A higher mobility sensitivity to reputation is always better for
      cooperation. A longer reputation memory favors cooperation, provided that the
      corresponding mobility sensitivity to reputation is strong enough. The
      microscopic perception of the effect of this mechanism is also given. Our results
      may shed some light on the role played by migration in the emergence and
      persistence of cooperation.

PMID- 22615741
TI  - Reduction in predator defense in the presence of neighbors in a colonial fish.
AB  - Predation pressure has long been considered a leading explanation of colonies,
      where close neighbors may reduce predation via dilution, alarming or group
      predator attacks. Attacking predators may be costly in terms of energy and
      survival, leading to the question of how neighbors contribute to predator
      deterrence in relationship to each other. Two hypotheses explaining the relative
      efforts made by neighbors are byproduct-mutualism, which occurs when breeders
      inadvertently attack predators by defending their nests, and reciprocity, which
      occurs when breeders deliberately exchange predator defense efforts with
      neighbors. Most studies investigating group nest defense have been performed with
      birds. However, colonial fish may constitute a more practical model system for an
      experimental approach because of the greater ability of researchers to manipulate
      their environment. We investigated in the colonial fish, Neolamprologus
      caudopunctatus, whether prospecting pairs preferred to breed near conspecifics or
      solitarily, and how breeders invested in anti-predator defense in relation to
      neighbors. In a simple choice test, prospecting pairs selected breeding sites
      close to neighbors versus a solitary site. Predators were then sequentially
      presented to the newly established test pairs, the previously established
      stimulus pairs or in between the two pairs. Test pairs attacked the predator
      eight times more frequently when they were presented on their non-neighbor side
      compared to between the two breeding sites, where stimulus pairs maintained high
      attack rates. Thus, by joining an established pair, test pairs were able to
      reduce their anti-predator efforts near neighbors, at no apparent cost to the
      stimulus pairs. These findings are unlikely to be explained by reciprocity or
      byproduct-mutualism. Our results instead suggest a commensal relationship in
      which new pairs exploit the high anti-predator efforts of established pairs,
      which invest similarly with or without neighbors. Further studies are needed to
      determine the scope of commensalism as an anti-predator strategy in colonial
      animals.

PMID- 22615742
TI  - Urinary proteomics to support diagnosis of stroke.
AB  - Accurate diagnosis in suspected ischaemic stroke can be difficult. We explored
      the urinary proteome in patients with stroke (n = 69), compared to controls (n =
      33), and developed a biomarker model for the diagnosis of stroke. We performed
      capillary electrophoresis online coupled to micro-time-of-flight mass
      spectrometry. Potentially disease-specific peptides were identified and a
      classifier based on these was generated using support vector machine-based
      software. Candidate biomarkers were sequenced by liquid chromatography-tandem
      mass spectrometry. We developed two biomarker-based classifiers, employing 14
      biomarkers (nominal p-value <0.004) or 35 biomarkers (nominal p-value <0.01).
      When tested on a blinded test set of 47 independent samples, the classification
      factor was significantly different between groups; for the 35 biomarker model,
      median value of the classifier was 0.49 (-0.30 to 1.25) in cases compared to 
      1.04 (IQR -1.86 to -0.09) in controls, p<0.001. The 35 biomarker classifier gave
      sensitivity of 56%, specificity was 93% and the AUC on ROC analysis was 0.86.
      This study supports the potential for urinary proteomic biomarker models to
      assist with the diagnosis of acute stroke in those with mild symptoms. We now
      plan to refine further and explore the clinical utility of such a test in large
      prospective clinical trials.

PMID- 22615740
TI  - Targeting tumour-initiating cells with TRAIL based combination therapy ensures
      complete and lasting eradication of multiple myeloma tumours in vivo.
AB  - Multiple myeloma (MM) remains an incurable disease despite improvements to
      available treatments and efforts to identify new drug targets. Consequently new
      approaches are urgently required. We have investigated the potential of native
      tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), in combination
      with doxorubicin, to induce apoptotic cell death in phenotypically distinct
      populations of myeloma cells in vitro and in vivo. The cytotoxic potential of
      TRAIL alone, and in combination with DOX, was assessed in vitro in purified
      CD138(+) and CD138(-) cells from the MM cell lines and samples from patients with
      MM. Mouse xenografts obtained by implanting CD138(-) MM cells were used to assess
      the efficacy of TRAIL, alone and in combination with DOX, in vivo. CD138(-) cells
      were shown to be more resistant to the cytotoxic activity of TRAIL than CD138(+)
      cells and have reduced expression of TRAIL death receptors. This resistance
      results in preferential killing of CD 138(+) cells during exposure of MM culture
      to TRAIL. Furthermore, prolonged exposure results in the appearance of TRAIL
      resistant CD138(-) cells. However, when TRAIL is combined with doxorubicin, this
      results in complete eradication of MM cells in vivo. Most importantly, this
      treatment successfully eliminates CD138(-) cells implicated in tumour initiation
      and growth maintenance. These findings may explain the failure of current
      therapies and offer a promising new approach in the quest to cure MM and
      disseminated cancers.

PMID- 22615743
TI  - Clusters of sudden unexplained death associated with the mushroom, Trogia
      venenata, in rural Yunnan Province, China.
AB  - INTRODUCTION: Since the late 1970's, time-space clusters of sudden unexplained
      death (SUD) in northwest Yunnan, China have alarmed the public and health
      authorities. From 2006-2009, we initiated enhanced surveillance for SUD to
      identify a cause, and we warned villagers to avoid eating unfamiliar mushrooms.
      METHODS: We established surveillance for SUD, defined as follows: sudden onset of
      serious, unexplained physical impairment followed by death in <24 hours. A mild
      case was onset of any illness in a member of the family or close socially related
      group of a SUD victim within 1 week of a SUD. We interviewed witnesses of SUD and
      mild case-persons to identify exposures to potentially toxic substances. We
      tested blood from mild cases, villagers, and for standard biochemical, enzyme,
      and electrolyte markers of disease. RESULTS: We identified 33 SUD, a 73% decline
      from 2002-2005, distributed among 21 villages of 11 counties. We found a
      previously undescribed mushroom, Trogia venenata, was eaten by 5 of 7 families
      with SUD clusters compared to 0 of 31 other control-families from the same
      villages. In T. venenata-exposed persons SUD was characterized by sudden loss of
      consciousness during normal activities. This mushroom grew nearby 75% of 61
      villages that had time-space SUD clusters from 1975 to 2009 compared to 17% of 18
      villages with only single SUD (p<0.001, Fisher's exact test). DISCUSSION:
      Epidemiologic data has implicated T. venenata as a probable cause of clusters of
      SUD in northwestern Yunnan Province. Warnings to villagers about eating this
      mushroom should continue.

PMID- 22615745
TI  - Interactions between soil habitat and geographic range location affect plant
      fitness.
AB  - Populations are often found on different habitats at different geographic
      locations. This habitat shift may be due to biased dispersal, physiological
      tolerances or biotic interactions. To explore how fitness of the native plant
      Chamaecrista fasciculata depends on habitat within, at and beyond its range edge,
      we planted seeds from five populations in two soil substrates at these geographic
      locations. We found that with reduced competition, lifetime fitness was always
      greater or equivalent in one habitat type, loam soils, though early-season
      survival was greater on sand soils. At the range edge, natural populations are
      typically found on sand soil habitats, which are also less competitive
      environments. Early-season survival and fitness differed among source
      populations, and when transplanted beyond the range edge, range edge populations
      had greater fitness than interior populations. Our results indicate that even
      when the optimal soil substrate for a species does not change with geographic
      range location, the realized niche of a species may be restricted to sub-optimal
      habitats at the range edge because of the combined effects of differences in
      abiotic and biotic effects (e.g. competitors) between substrates.

PMID- 22615744
TI  - Reduced mature microRNA levels in association with dicer loss in human temporal
      lobe epilepsy with hippocampal sclerosis.
AB  - Hippocampal sclerosis (HS) is a common pathological finding in patients with
      temporal lobe epilepsy (TLE) and is associated with altered expression of genes
      controlling neuronal excitability, glial function, neuroinflammation and cell
      death. MicroRNAs (miRNAs), a class of small non-coding RNAs, function as post
      transcriptional regulators of gene expression and are critical for normal brain
      development and function. Production of mature miRNAs requires Dicer, an RNAase
      III, loss of which has been shown to cause neuronal and glial dysfunction,
      seizures, and neurodegeneration. Here we investigated miRNA biogenesis in
      hippocampal and neocortical resection specimens from pharmacoresistant TLE
      patients and autopsy controls. Western blot analysis revealed protein levels of
      Dicer were significantly lower in certain TLE patients with HS. Dicer levels were
      also reduced in the hippocampus of mice subject to experimentally-induced
      epilepsy. To determine if Dicer loss was associated with altered miRNA
      processing, we profiled levels of 380 mature miRNAs in control and TLE-HS
      samples. Expression of nearly 200 miRNAs was detected in control human
      hippocampus. In TLE-HS samples there was a large-scale reduction of miRNA
      expression, with 51% expressed at lower levels and a further 24% not detectable.
      Primary transcript (pri-miRNAs) expression levels for several tested miRNAs were
      not different between control and TLE-HS samples. These findings suggest loss of
      Dicer and failure of mature miRNA expression may be a feature of the
      pathophysiology of HS in patients with TLE.

PMID- 22615746
TI  - Does the reading of different orthographies produce distinct brain activity
      patterns? An ERP study.
AB  - Orthographies vary in the degree of transparency of spelling-sound
      correspondence. These range from shallow orthographies with transparent grapheme
      phoneme relations, to deep orthographies, in which these relations are opaque.
      Only a few studies have examined whether orthographic depth is reflected in brain
      activity. In these studies a between-language design was applied, making it
      difficult to isolate the aspect of orthographic depth. In the present work this
      question was examined using a within-subject-and-language investigation. The
      participants were speakers of Hebrew, as they are skilled in reading two forms of
      script transcribing the same oral language. One form is the shallow pointed
      script (with diacritics), and the other is the deep unpointed script (without
      diacritics). Event-related potentials (ERPs) were recorded while skilled readers
      carried out a lexical decision task in the two forms of script. A visual non
      orthographic task controlled for the visual difference between the scripts
      (resulting from the addition of diacritics to the pointed script only). At an
      early visual-perceptual stage of processing (~165 ms after target onset), the
      pointed script evoked larger amplitudes with longer latencies than the unpointed
      script at occipital-temporal sites. However, these effects were not restricted to
      orthographic processing, and may therefore have reflected, at least in part, the
      visual load imposed by the diacritics. Nevertheless, the results implied that
      distinct orthographic processing may have also contributed to these effects. At
      later stages (~340 ms after target onset) the unpointed script elicited larger
      amplitudes than the pointed one with earlier latencies. As this latency has been
      linked to orthographic-linguistic processing and to the classification of
      stimuli, it is suggested that these differences are associated with distinct
      lexical processing of a shallow and a deep orthography.

PMID- 22615747
TI  - Dysregulated nephrin in diabetic nephropathy of type 2 diabetes: a cross
      sectional study.
AB  - BACKGROUND: Podocyte specific proteins are dysregulated in diabetic nephropathy,
      though the extent of their expression loss is not identical and may be subject to
      different regulatory factors. Quantifying the degree of loss may help identify
      the most useful protein to use as an early biomarker of diabetic nephropathy.
      METHODOLOGY/PRINCIPAL FINDINGS: Protein expression of synaptopodin, podocin and
      nephrin were quantified in 15 Type 2 diabetic renal biopsies and 12 control
      patients. We found statistically significant downregulation of synaptopodin
      (P<0.0001), podocin (P = 0.0002), and nephrin (P<0.0001) in kidney biopsies of
      diabetic nephropathy as compared with controls. Urinary nephrin levels
      (nephrinuria) were then measured in 66 patients with Type 2 diabetes and 10
      healthy controls by an enzyme-linked immunosorbent assay (Exocell, Philadelphia,
      PA). When divided into groups according to normo-, micro-, and macroalbuminuria,
      nephrinuria was found to be present in 100% of diabetic patients with micro- and
      macroalbuminuria, as well as 54% of patients with normoalbuminuria. Nephrinuria
      also correlated significantly with albuminuria (rho = 0.89, p<0.001), systolic
      blood pressure (rho = 0.32, p = 0.007), and correlated negatively with serum
      albumin (rho = -0.48, p<0.0001) and eGFR (rho = -0.33, p = 0.005).
      CONCLUSIONS/SIGNIFICANCE: These data suggest that key podocyte-specific protein
      expressions are significantly and differentially downregulated in diabetic
      nephropathy. The finding that nephrinuria is observed in a majority of these
      normoalbuminuric patients demonstrates that it may precede microalbuminuria. If
      further research confirms nephrinuria to be a biomarker of pre-clinical diabetic
      nephropathy, it would shed light on podocyte metabolism in disease, and raise the
      possibility of new and earlier therapeutic targets.

PMID- 22615748
TI  - Absence of XMRV and closely related viruses in primary prostate cancer tissues
      used to derive the XMRV-infected cell line 22Rv1.
AB  - The 22Rv1 cell line is widely used for prostate cancer research and other studies
      throughout the world. These cells were established from a human prostate tumor,
      CWR22, that was serially passaged in nude mice and selected for androgen
      independence. The 22Rv1 cells are known to produce high titers of xenotropic
      murine leukemia virus-related virus (XMRV). Recent studies suggested that XMRV
      was inadvertently created in the 1990's when two murine leukemia virus (MLV)
      genomes (pre-XMRV1 and pre-XMRV-2) recombined during passaging of the CWR22 tumor
      in mice. The conclusion that XMRV originated from mice and not the patient was
      based partly on the failure to detect XMRV in early CWR22 xenografts. While that
      deduction is certainly justified, we examined the possibility that a closely
      related virus could have been present in primary tumor tissue. Here we report
      that we have located the original prostate tumor tissue excised from patient
      CWR22 and have assayed the corresponding DNA by PCR and the tissue sections by
      fluorescence in situ hybridization for the presence of XMRV or a similar virus.
      The primary tumor tissues lacked mouse DNA as determined by PCR for
      intracisternal A type particle DNA, thus avoiding one of the limitations of
      studying xenografts. We show that neither XMRV nor a closely related virus was
      present in primary prostate tissue of patient CWR22. Our findings confirm and
      reinforce the conclusion that XMRV is a recombinant laboratory-generated mouse
      virus that is highly adapted for human prostate cancer cells.

PMID- 22615749
TI  - No biological evidence of XMRV in blood or prostatic fluid from prostate cancer
      patients.
AB  - BACKGROUND: XMRV (xenotropic murine leukemia virus-related virus) was initially
      discovered in association with prostate cancer and later with chronic fatigue
      syndrome (CFS). Its association with CFS is now largely discredited, and current
      results support a laboratory origin for XMRV with no reproducible evidence for
      infection of humans. However, some results indicating the presence of XMRV in
      prostate cancer are difficult to attribute to sample contamination. Here we have
      sought biological evidence that might confirm the presence of XMRV in prostate
      cancer samples previously having tested positive. METHODS AND RESULTS: We have
      tested for infectious XMRV and neutralizing antibodies against XMRV in blood
      plasma from 29 subjects with prostate cancer, and for infectious XMRV in prostate
      secretions from another five prostate cancer subjects. Nine of these subjects had
      previously tested positive for XMRV by PCR or by virus assay. We did not detect
      XMRV or related retroviruses in any sample, and the neutralizing activities of
      the plasma samples were all very low, a result inconsistent with XMRV infection
      of the plasma donors. CONCLUSIONS: We find no evidence for XMRV infection of any
      human subject tested, either by assay for infectious virus or for neutralizing
      antibodies. Our results are consistent with the majority of published studies on
      XMRV, which find that XMRV is not present in humans. The observed low to
      undetectable XMRV neutralization by human plasma indicates a lack of innate
      restriction of XMRV replication by soluble factors in human blood.

PMID- 22615750
TI  - The tyrphostin agent AG490 prevents and reverses type 1 diabetes in NOD mice.
AB  - BACKGROUND: Recent studies in the NOD (non-obese diabetic) mouse model of type 1
      diabetes (T1D) support the notion that tyrosine kinase inhibitors have the
      potential for modulating disease development. However, the therapeutic effects of
      AG490 on the development of T1D are unknown. MATERIALS AND METHODS: Female NOD
      mice were treated with AG490 (i.p, 1 mg/mouse) or DMSO starting at either 4 or 8
      week of age, for five consecutive week, then once per week for 5 additional week.
      Analyses for the development and/or reversal of diabetes, insulitis, adoptive
      transfer, and other mechanistic studies were performed. RESULTS: AG490
      significantly inhibited the development of T1D (p = 0.02, p = 0.005; at two
      different time points). Monotherapy of newly diagnosed diabetic NOD mice with
      AG490 markedly resulted in disease remission in treated animals (n = 23) in
      comparision to the absolute inability (0%; 0/10, p = 0.003, Log-rank test) of
      DMSO and sustained eugluycemia was maintained for several months following drug
      withdrawal. Interestingly, adoptive transfer of splenocytes from AG490 treated
      NOD mice failed to transfer diabetes to recipient NOD.Scid mice. CD4 T-cells as
      well as bone marrow derived dendritic cells (BMDCs) from AG490 treated mice,
      showed higher expression of Foxp3 (p<0.004) and lower expression of co
      stimulatory molecules, respectively. Screening of the mouse immune response gene
      arrary indicates that expression of costimulaotry molecule Ctla4 was upregulated
      in CD4+ T-cell in NOD mice treated with AG490, suggesting that AG490 is not a
      negative regulator of the immune system. CONCLUSION: The use of such agents,
      given their extensive safety profiles, provides a strong foundation for their
      translation to humans with or at increased risk for the disease.

PMID- 22615751
TI  - Telephone consultation for improving health of people living with or at risk of
      HIV: a systematic review.
AB  - BACKGROUND: Low cost, effective interventions are needed to deal with the major
      global burden of HIV/AIDS. Telephone consultation offers the potential to improve
      health of people living with HIV/AIDS cost-effectively and to reduce the burden
      on affected people and health systems. The aim of this systematic review was to
      assess the effectiveness of telephone consultation for HIV/AIDS care. METHODS: We
      undertook a comprehensive search of peer-reviewed and grey literature. Two
      authors independently screened citations, extracted data and assessed the quality
      of randomized controlled trials which compared telephone interventions with
      control groups for HIV/AIDS care. Telephone interventions were voice calls with
      landlines or mobile phones. We present a narrative overview of the results as the
      obtained trials were highly heterogeneous in design and therefore the data could
      not be pooled for statistical analysis. RESULTS: The search yielded 3321
      citations. Of these, nine studies involving 1162 participants met the inclusion
      criteria. The telephone was used for giving HIV test results (one trial) and for
      delivering behavioural interventions aimed at improving mental health (four
      trials), reducing sexual transmission risk (one trial), improving medication
      adherence (two trials) and smoking cessation (one trial). Limited effectiveness
      of the intervention was found in the trial giving HIV test results, in one trial
      supporting medication adherence and in one trial for smoking cessation by
      telephone. CONCLUSIONS: We found some evidence of the benefits of interventions
      delivered by telephone for the health of people living with HIV or at risk of
      HIV. However, only limited conclusions can be drawn as we only found nine studies
      for five different interventions and they mainly took place in the United States.
      Nevertheless, given the high penetration of low-cost mobile phones in countries
      with high HIV endemicity, more evidence is needed on how telephone consultation
      can aid in the delivery of HIV prevention, treatment and care.

PMID- 22615752
TI  - Functional analysis of conserved motifs in influenza virus PB1 protein.
AB  - The influenza virus RNA polymerase complex is a heterotrimer composed of the PB1,
      PB2, and PA subunits. PB1, the catalytic core and structural backbone of the
      polymerase, possesses four highly conserved amino acid motifs that are present
      among all viral RNA-dependent RNA polymerases. A previous study demonstrated the
      importance of several of these conserved amino acids in PB1 for influenza
      polymerase activity through mutational analysis. However, a small number of
      viruses isolated in nature possesses non-consensus amino acids in one of the four
      motifs, most of which have not been tested for their replicative ability. Here,
      we assessed the transcription/replication activities of 25 selected PB1 mutations
      found in natural isolates by using minireplicon assays in human and avian cells.
      Most of the mutations tested significantly reduced polymerase activity. One
      exception was mutation K480R, observed in several pandemic (H1N1) 2009 viruses,
      which slightly increased polymerase activity relative to wild-type. However, in
      the background of the pandemic A/California/04/2009 (H1N1) virus, this mutation
      did not affect virus titers in cell culture. Our results further demonstrate the
      functional importance of the four conserved PB1 motifs in influenza virus
      transcription/replication. The finding of natural isolates with non-consensus PB1
      motifs that are nonfunctional in minireplicon assays suggests compensatory
      mutations and/or mixed infections which may have 'rescued' the inactive PB1
      protein.

PMID- 22615753
TI  - Does the precision of a biological clock depend upon its period? Effects of the
      duper and tau mutations in Syrian hamsters.
AB  - Mutations which alter the feedback loops that generate circadian rhythms may
      provide insight into their insensitivity to perturbation robustness) and their
      consistency of period (precision). I examined relationships between endogenous
      period, activity and rest (tau(DD), alpha and rho) in Syrian hamsters using two
      different mutations, duper and tau, both of which speed up the circadian clock. I
      generated 8 strains of hamsters that are homozygous or heterozygous for the tau,
      duper, and wild type alleles in all combinations. The endogenous period of
      activity onsets among these strains ranged from 17.94+0.04 to 24.13 +/- 0.04 h.
      Contrary to predictions, the variability of period was unrelated to its absolute
      value: all strains showed similar variability of tau(DD) when activity onsets and
      acrophase were used as phase markers. The tau(DD) of activity offsets was more
      variable than onsets but also differed little between genotypes. Cycle variation
      and precision were not correlated with tau(DD) within any strain, and only weakly
      correlated when all strains are considered together. Only in animals homozygous
      for both mutations (super duper hamsters) were cycle variation and precision
      reduced. Rhythm amplitude differed between strains and was positively correlated
      with tau(DD) and precision. All genotypes showed negative correlations between
      alpha and rho. This confirms the expectation that deviations in the duration of
      subjective day and night should offset one another in order to conserve circadian
      period, even though homeostatic maintenance of energy reserves predicts that
      longer intervals of activity or rest would be followed by longer durations of
      rest or activity. Females consistently showed greater variability of the period
      of activity onset and acrophase, and of alpha, but variability of the period of
      offset differed between sexes only in super duper hamsters. Despite the
      differences between genotypes in tau(DD), rho was consistently more strongly
      correlated with the preceding than the succeeding alpha.

PMID- 22615754
TI  - The role of gender information in pronoun resolution: evidence from Chinese.
AB  - Although previous studies have consistently demonstrated that gender information
      is used to resolve pronouns, the mechanisms underlying the use of gender
      information continue to be controversial. The present study used event-related
      potentials (ERPs) to investigate whether working memory modulates the effect of
      gender information on pronoun resolution. The critical pronoun agreed or
      disagreed with its antecedent in gender. Moreover, the distance between a pronoun
      and its antecedent was varied to assess the influence of working memory. Compared
      with the congruent pronouns, the incongruent pronouns elicited an N400 effect in
      the short distance condition and a P600 effect in the long distance condition.
      The results suggest that the effect of gender information on pronoun
      comprehension is modulated by working memory.

PMID- 22615755
TI  - Numerical integration of the master equation in some models of stochastic
      epidemiology.
AB  - The processes by which disease spreads in a population of individuals are
      inherently stochastic. The master equation has proven to be a useful tool for
      modeling such processes. Unfortunately, solving the master equation analytically
      is possible only in limited cases (e.g., when the model is linear), and thus
      numerical procedures or approximation methods must be employed. Available
      approximation methods, such as the system size expansion method of van Kampen,
      may fail to provide reliable solutions, whereas current numerical approaches can
      induce appreciable computational cost. In this paper, we propose a new numerical
      technique for solving the master equation. Our method is based on a more
      informative stochastic process than the population process commonly used in the
      literature. By exploiting the structure of the master equation governing this
      process, we develop a novel technique for calculating the exact solution of the
      master equation--up to a desired precision--in certain models of stochastic
      epidemiology. We demonstrate the potential of our method by solving the master
      equation associated with the stochastic SIR epidemic model. MATLAB software that
      implements the methods discussed in this paper is freely available as Supporting
      Information S1.

PMID- 22615756
TI  - Keeping the faith: African American faith leaders' perspectives and
      recommendations for reducing racial disparities in HIV/AIDS infection.
AB  - In Philadelphia, 66% of new HIV infections are among African Americans and 2% of
      African Americans are living with HIV. The city of Philadelphia has among the
      largest numbers of faith institutions of any city in the country. Although faith
      based institutions play an important role in the African American community,
      their response to the AIDS epidemic has historically been lacking. We convened 38
      of Philadelphia's most influential African American faith leaders for in-depth
      interviews and focus groups examining the role of faith-based institutions in HIV
      prevention. Participants were asked to comment on barriers to engaging faith
      based leaders in HIV prevention and were asked to provide normative
      recommendations for how African American faith institutions can enhance HIV/AIDS
      prevention and reduce racial disparities in HIV infection. Many faith leaders
      cited lack of knowledge about Philadelphia's racial disparities in HIV infection
      as a common reason for not previously engaging in HIV programs; others noted
      their congregations' existing HIV prevention and outreach programs and shared
      lessons learned. Barriers to engaging the faith community in HIV prevention
      included: concerns about tacitly endorsing extramarital sex by promoting condom
      use, lack of educational information appropriate for a faith-based audience, and
      fear of losing congregants and revenue as a result of discussing human sexuality
      and HIV/AIDS from the pulpit. However, many leaders expressed a moral imperative
      to respond to the AIDS epidemic, and believed clergy should play a greater role
      in HIV prevention. Many participants noted that controversy surrounding
      homosexuality has historically divided the faith community and prohibited an
      appropriate response to the epidemic; many expressed interest in balancing
      traditional theology with practical public health approaches to HIV prevention.
      Leaders suggested the faith community should: promote HIV testing, including
      during or after worship services and in clinical settings; integrate HIV/AIDS
      topics into health messaging and sermons; couch HIV/AIDS in social justice, human
      rights and public health language rather than in sexual risk behavior terms;
      embrace diverse approaches to HIV prevention in their houses of worship; conduct
      community outreach and host educational sessions for youth; and collaborate on a
      citywide, interfaith HIV testing and prevention campaign to combat stigma and
      raise awareness about the African American epidemic. Many African American faith
      based leaders are poised to address racial disparities in HIV infection. HIV
      prevention campaigns should integrate leaders' recommendations for tailoring HIV
      prevention for a faith-based audience.

PMID- 22615757
TI  - alpha-Synuclein genetic variants predict faster motor symptom progression in
      idiopathic Parkinson disease.
AB  - Currently, there are no reported genetic predictors of motor symptom progression
      in Parkinson's disease (PD). In familial PD, disease severity is associated with
      higher alpha-synuclein (SNCA) expression levels, and in postmortem studies
      expression varies with SNCA genetic variants. Furthermore, SNCA is a well-known
      risk factor for PD occurrence. We recruited Parkinson's patients from the
      communities of three central California counties to investigate the influence of
      SNCA genetic variants on motor symptom progression in idiopathic PD. We
      repeatedly assessed this cohort of patients over an average of 5.1 years for
      motor symptom changes employing the Unified Parkinson's Disease Rating Scale
      (UPDRS). Of 363 population-based incident PD cases diagnosed less than 3 years
      from baseline assessment, 242 cases were successfully re-contacted and 233 were
      re-examined at least once. Of subjects lost to follow-up, 69% were due to death.
      Adjusting for covariates, risk of faster decline of motor function as measured by
      annual increase in motor UPDRS exam score was increased 4-fold in carriers of the
      REP1 263bp promoter variant (OR 4.03, 95%CI:1.57-10.4). Our data also suggest a
      contribution to increased risk by the G-allele for rs356165 (OR 1.66; 95%CI:0.96
      2.88), and we observed a strong trend across categories when both genetic
      variants were considered (p for trend = 0.002). Our population-based study has
      demonstrated that SNCA variants are strong predictors of faster motor decline in
      idiopathic PD. SNCA may be a promising target for therapies and may help identify
      patients who will benefit most from early interventions. This is the first study
      to link SNCA to motor symptom decline in a longitudinal progression study.

PMID- 22615758
TI  - "Mind the trap": mindfulness practice reduces cognitive rigidity.
AB  - Two experiments examined the relation between mindfulness practice and cognitive
      rigidity by using a variation of the Einstellung water jar task. Participants
      were required to use three hypothetical jars to obtain a specific amount of
      water. Initial problems were solvable by the same complex formula, but in later
      problems ("critical" or "trap" problems) solving was possible by an additional
      much simpler formula. A rigidity score was compiled through perseverance of the
      complex formula. In Experiment 1, experienced mindfulness meditators received
      significantly lower rigidity scores than non-meditators who had registered for
      their first meditation retreat. Similar results were obtained in randomized
      controlled Experiment 2 comparing non-meditators who underwent an eight meeting
      mindfulness program with a waiting list group. The authors conclude that
      mindfulness meditation reduces cognitive rigidity via the tendency to be
      "blinded" by experience. Results are discussed in light of the benefits of
      mindfulness practice regarding a reduced tendency to overlook novel and adaptive
      ways of responding due to past experience, both in and out of the clinical
      setting.

PMID- 22615759
TI  - Manipulation of pre-target activity on the right frontal eye field enhances
      conscious visual perception in humans.
AB  - The right Frontal Eye Field (FEF) is a region of the human brain, which has been
      consistently involved in visuo-spatial attention and access to consciousness.
      Nonetheless, the extent of this cortical site's ability to influence specific
      aspects of visual performance remains debated. We hereby manipulated pre-target
      activity on the right FEF and explored its influence on the detection and
      categorization of low-contrast near-threshold visual stimuli. Our data show that
      pre-target frontal neurostimulation has the potential when used alone to induce
      enhancements of conscious visual detection. More interestingly, when FEF
      stimulation was combined with visuo-spatial cues, improvements remained present
      only for trials in which the cue correctly predicted the location of the
      subsequent target. Our data provide evidence for the causal role of the right FEF
      pre-target activity in the modulation of human conscious vision and reveal the
      dependence of such neurostimulatory effects on the state of activity set up by
      cue validity in the dorsal attentional orienting network.

PMID- 22615760
TI  - Egocentric social network structure, health, and pro-social behaviors in a
      national panel study of Americans.
AB  - Using a population-based, panel survey, we study how egocentric social networks
      change over time, and the relationship between egocentric network properties and
      health and pro-social behaviors. We find that the number of prosocial activities
      is strongly positively associated with having more friends, or an increase in
      degree, with approximately 0.04 more prosocial behaviors expected for every
      friend added. Moreover, having more friends is associated with an improvement in
      health, while being healthy and prosocial is associated with closer
      relationships. Specifically, a unit increase in health is associated with an
      expected 0.45 percentage-point increase in average closeness, while adding a
      prosocial activity is associated with a 0.46 percentage-point increase in the
      closeness of one's relationships. Furthermore, a tradeoff between degree and
      closeness of social contacts was observed. As the number of close social contacts
      increases by one, the estimated average closeness of each individual contact
      decreases by approximately three percentage-points. The increased awareness of
      the importance of spillover effects in health and health care makes the
      ascertainment of egocentric social networks a valuable complement to
      investigations of the relationship between socioeconomic factors and health.

PMID- 22615761
TI  - Reputation-based conditional interaction supports cooperation in well-mixed
      prisoner's dilemmas.
AB  - In the well-mixed prisoner's dilemma game, individuals are typically assumed to
      have no choice about whether to interact with other individuals in the
      population. In this paper, we instead consider reputation-based conditional
      interaction and its consequences for the evolution of cooperation. Each
      individual has a tolerance range, and only interacts with other individuals whose
      reputation lies within its tolerance range in a chosen sample of the population.
      Reputation contains information about the number of interaction partners an
      individual has just cooperated with. We find that the introduction of conditional
      interaction promotes cooperation in well-mixed populations, and there exist
      moderate tolerance ranges for which this effect is maximized. For a given
      tolerance range, there is a critical cost-to-benefit ratio below which
      cooperation can be promoted. Interestingly, we find that if cooperation evolves,
      different cooperators' interaction clusters are typically maintained in the
      population, each around a different reputation level. We further investigate some
      properties of these cooperators' clusters. Moreover, we examine the effects of
      the sample number on the evolution of cooperation. Our results highlight the
      importance of the detailed consideration of modes of interaction for the
      evolution of cooperation in well-mixed populations.

PMID- 22615762
TI  - Election turnout statistics in many countries: similarities, differences, and a
      diffusive field model for decision-making.
AB  - We study in details the turnout rate statistics for 77 elections in 11 different
      countries. We show that the empirical results established in a previous paper for
      French elections appear to hold much more generally. We find in particular that
      the spatial correlation of turnout rates decay logarithmically with distance in
      all cases. This result is quantitatively reproduced by a decision model that
      assumes that each voter makes his mind as a result of three influence terms: one
      totally idiosyncratic component, one city-specific term with short-ranged
      fluctuations in space, and one long-ranged correlated field which propagates
      diffusively in space. A detailed analysis reveals several interesting features:
      for example, different countries have different degrees of local heterogeneities
      and seem to be characterized by a different propensity for individuals to conform
      to the cultural norm. We furthermore find clear signs of herding (i.e., strongly
      correlated decisions at the individual level) in some countries, but not in
      others.

PMID- 22615763
TI  - Cystatin a, a potential common link for mutant myocilin causative glaucoma.
AB  - Myocilin (MYOC) is a 504 aa secreted glycoprotein induced by stress factors in
      the trabecular meshwork tissue of the eye, where it was discovered. Mutations in
      MYOC are linked to glaucoma. The glaucoma phenotype of each of the different MYOC
      mutation varies, but all of them cause elevated intraocular pressure (IOP). In
      cells, forty percent of wild-type MYOC is cleaved by calpain II, a cysteine
      protease. This proteolytic process is inhibited by MYOC mutants. In this study,
      we investigated the molecular mechanisms by which MYOC mutants cause glaucoma. We
      constructed adenoviral vectors with variants Q368X, R342K, D380N, K423E, and
      overexpressed them in human trabecular meshwork cells. We analyzed expression
      profiles with Affymetrix U133Plus2 GeneChips using wild-type and null viruses as
      controls. Analysis of trabecular meshwork relevant mechanisms showed that the
      unfolded protein response (UPR) was the most affected. Search for individual
      candidate genes revealed that genes that have been historically connected to
      trabecular meshwork physiology and pathology were altered by the MYOC mutants.
      Some of those had known MYOC associations (MMP1, PDIA4, CALR, SFPR1) while others
      did not (EDN1, MGP, IGF1, TAC1). Some, were top-changed in only one mutant
      (LOXL1, CYP1B1, FBN1), others followed a mutant group pattern. Some of the genes
      were new (RAB39B, STC1, CXCL12, CSTA). In particular, one selected gene, the
      cysteine protease inhibitor cystatin A (CSTA), was commonly induced by all
      mutants and not by the wild-type. Subsequent functional analysis of the selected
      gene showed that CSTA was able to reduce wild-type MYOC cleavage in primary
      trabecular meshwork cells while an inactive mutated CSTA was not. These findings
      provide a new molecular understanding of the mechanisms of MYOC-causative
      glaucoma and reveal CSTA, a serum biomarker for cancer, as a potential biomarker
      and drug for the treatment of MYOC-induced glaucoma.

PMID- 22615764
TI  - SH3 domain tyrosine phosphorylation--sites, role and evolution.
AB  - BACKGROUND: SH3 domains are eukaryotic protein domains that participate in a
      plethora of cellular processes including signal transduction, proliferation, and
      cellular movement. Several studies indicate that tyrosine phosphorylation could
      play a significant role in the regulation of SH3 domains. RESULTS: To explore the
      incidence of the tyrosine phosphorylation within SH3 domains we queried the
      PhosphoSite Plus database of phosphorylation sites. Over 100 tyrosine
      phosphorylations occurring on 20 different SH3 domain positions were identified.
      The tyrosine corresponding to c-Src Tyr-90 was by far the most frequently
      identified SH3 domain phosphorylation site. A comparison of sequences around this
      tyrosine led to delineation of a preferred sequence motif ALYD(Y/F). This motif
      is present in about 15% of human SH3 domains and is structurally well conserved.
      We further observed that tyrosine phosphorylation is more abundant than serine or
      threonine phosphorylation within SH3 domains and other adaptor domains, such as
      SH2 or WW domains. Tyrosine phosphorylation could represent an important
      regulatory mechanism of adaptor domains. CONCLUSIONS: While tyrosine
      phosphorylation typically promotes signaling protein interactions via SH2 or PTB
      domains, its role in SH3 domains is the opposite - it blocks or prevents
      interactions. The regulatory function of tyrosine phosphorylation is most likely
      achieved by the phosphate moiety and its charge interfering with binding of
      polyproline helices of SH3 domain interacting partners.

PMID- 22615765
TI  - SOX2 gene regulates the transcriptional network of oncogenes and affects
      tumorigenesis of human lung cancer cells.
AB  - Recent studies demonstrated that cancer stem cells (CSCs) have higher
      tumorigenesis properties than those of differentiated cancer cells and that
      transcriptional factor-SOX2 plays a vital role in maintaining the unique
      properties of CSCs; however, the function and underlying mechanism of SOX2 in
      carcinogenesis of lung cancer are still elusive. This study applied
      immunohistochemistry to analyze the expression of SOX2 in human lung tissues of
      normal individuals as well as patients with adenocarcinoma, squamous cell
      carcinoma, and large cell and small cell carcinoma and demonstrated specific
      overexpression of SOX2 in all types of lung cancer tissues. This finding supports
      the notion that SOX2 contributes to the tumorigenesis of lung cancer cells and
      can be used as a diagnostic probe. In addition, obviously higher expression of
      oncogenes c-MYC, WNT1, WNT2, and NOTCH1 was detected in side population (SP)
      cells than in non-side population (NSP) cells of human lung adenocarcinoma cell
      line-A549, revealing a possible mechanism for the tenacious tumorigenic potential
      of CSCs. To further elucidate the function of SOX2 in tumorigenesis of cancer
      cells, A549 cells were established with expression of luciferase and doxycycline
      inducible shRNA targeting SOX2. We found silencing of SOX2 gene reduces the
      tumorigenic property of A549 cells with attenuated expression of c-MYC, WNT1,
      WNT2, and NOTCH1 in xenografted NOD/SCID mice. By using the RNA-Seq method, an
      additional 246 target cancer genes of SOX2 were revealed. These results present
      evidence that SOX2 may regulate the expression of oncogenes in CSCs to promote
      the development of human lung cancer.

PMID- 22615766
TI  - Serratamolide is a hemolytic factor produced by Serratia marcescens.
AB  - Serratia marcescens is a common contaminant of contact lens cases and lenses.
      Hemolytic factors of S. marcescens contribute to the virulence of this
      opportunistic bacterial pathogen. We took advantage of an observed hyper
      hemolytic phenotype of crp mutants to investigate mechanisms of hemolysis. A
      genetic screen revealed that swrW is necessary for the hyper-hemolysis phenotype
      of crp mutants. The swrW gene is required for biosynthesis of the biosurfactant
      serratamolide, previously shown to be a broad-spectrum antibiotic and to
      contribute to swarming motility. Multicopy expression of swrW or mutation of the
      hexS transcription factor gene, a known inhibitor of swrW expression, led to an
      increase in hemolysis. Surfactant zones and expression from an swrW
      transcriptional reporter were elevated in a crp mutant compared to the wild type.
      Purified serratamolide was hemolytic to sheep and murine red blood cells and
      cytotoxic to human airway and corneal limbal epithelial cells in vitro. The swrW
      gene was found in the majority of contact lens isolates tested. Genetic and
      biochemical analysis implicate the biosurfactant serratamolide as a hemolysin.
      This novel hemolysin may contribute to irritation and infections associated with
      contact lens use.

PMID- 22615767
TI  - Movement patterns for a critically endangered species, the leatherback turtle
      (Dermochelys coriacea), linked to foraging success and population status.
AB  - Foraging success for pelagic vertebrates may be revealed by horizontal and
      vertical movement patterns. We show markedly different patterns for leatherback
      turtles in the North Atlantic versus Eastern Pacific, which feed on gelatinous
      zooplankton that are only occasionally found in high densities. In the Atlantic,
      travel speed was characterized by two modes, indicative of high foraging success
      at low speeds (<15 km d(-1)) and transit at high speeds (20-45 km d(-1)). Only a
      single mode was evident in the Pacific, which occurred at speeds of 21 km d(-1)
      indicative of transit. The mean dive depth was more variable in relation to
      latitude but closer to the mean annual depth of the thermocline and nutricline
      for North Atlantic than Eastern Pacific turtles. The most parsimonious
      explanation for these findings is that Eastern Pacific turtles rarely achieve
      high foraging success. This is the first support for foraging behaviour
      differences between populations of this critically endangered species and
      suggests that longer periods searching for prey may be hindering population
      recovery in the Pacific while aiding population maintenance in the Atlantic.

PMID- 22615768
TI  - Atypical audiovisual speech integration in infants at risk for autism.
AB  - The language difficulties often seen in individuals with autism might stem from
      an inability to integrate audiovisual information, a skill important for language
      development. We investigated whether 9-month-old siblings of older children with
      autism, who are at an increased risk of developing autism, are able to integrate
      audiovisual speech cues. We used an eye-tracker to record where infants looked
      when shown a screen displaying two faces of the same model, where one face is
      articulating/ba/and the other/ga/, with one face congruent with the syllable
      sound being presented simultaneously, the other face incongruent. This method was
      successful in showing that infants at low risk can integrate audiovisual speech:
      they looked for the same amount of time at the mouths in both the fusible
      visual/ga/- audio/ba/and the congruent visual/ba/- audio/ba/displays, indicating
      that the auditory and visual streams fuse into a McGurk-type of syllabic percept
      in the incongruent condition. It also showed that low-risk infants could perceive
      a mismatch between auditory and visual cues: they looked longer at the mouth in
      the mismatched, non-fusible visual/ba/- audio/ga/display compared with the
      congruent visual/ga/- audio/ga/display, demonstrating that they perceive an
      uncommon, and therefore interesting, speech-like percept when looking at the
      incongruent mouth (repeated ANOVA: displays x fusion/mismatch conditions
      interaction: F(1,16) = 17.153, p = 0.001). The looking behaviour of high-risk
      infants did not differ according to the type of display, suggesting difficulties
      in matching auditory and visual information (repeated ANOVA, displays x
      conditions interaction: F(1,25) = 0.09, p = 0.767), in contrast to low-risk
      infants (repeated ANOVA: displays x conditions x low/high-risk groups
      interaction: F(1,41) = 4.466, p = 0.041). In some cases this reduced ability
      might lead to the poor communication skills characteristic of autism.

PMID- 22615769
TI  - The role of primary care in service provision for people with severe mental
      illness in the United Kingdom.
AB  - BACKGROUND: Severe mental illness is a serious and potentially life changing set
      of conditions. This paper describes and analyses patient characteristics and
      service usage over one year of a representative cohort of people with a diagnosis
      of severe mental illness across England, including contacts with primary and
      secondary care and continuity of care. METHODS AND FINDINGS: Data were collected
      from primary care patient notes (n = 1150) by trained nurses from 64 practices in
      England, covering all service contacts from 1(st) April 2008 to 31st March 2009.
      The estimated national rate of patients seen only in primary care in the period
      was 31.1% (95% C.I. 27.2% to 35.3%) and the rates of schizophrenia and bipolar
      disorder were 56.8% (95% C.I. 52.3% to 61.2%) and 37.9% (95% C.I. 33.7% to
      42.2%). In total, patients had 7,961 consultations within primary care and 1,993
      contacts with mental health services (20% of the total). Unemployed individuals
      diagnosed more recently were more likely to have contact with secondary care. Of
      those seen in secondary care, 61% had at most two secondary care contacts in the
      period. Median annual consultation rates with GPs were lower than have been
      reported for previous years and were only slightly above the general population.
      Relational continuity in primary care was poor for 21% of patients (Modified
      Modified Continuity Index = <0.5), and for almost a third of new referrals to
      mental health services the primary care record contained no information on the
      referral outcome. CONCLUSIONS: Primary care is centrally involved in the care of
      people with serious mental illness, but primary care and cross-boundary
      continuity is poor for a substantial proportion. Research is needed to determine
      the impact of poor continuity on patient outcomes, and above all, the impact of
      new collaborative ways of working at the primary/secondary care interface.

PMID- 22615770
TI  - Sphingosine kinase 1 deficiency exacerbates LPS-induced neuroinflammation.
AB  - The pathogenesis of inflammation in the central nervous system (CNS), which
      contributes to numerous neurodegenerative diseases and results in encephalopathy
      and neuroinflammation, is poorly understood. Sphingolipid metabolism plays a
      crucial role in maintaining cellular processes in the CNS, and thus mediates the
      various pathological consequences of inflammation. For a better understanding of
      the role of sphingosine kinase activation during neuroinflammation, we developed
      a bacterial lipopolysaccharide (LPS)-induced brain injury model. The onset of the
      inflammatory response was observed beginning 4 hours after intracerebral
      injection of LPS into the lateral ventricles of the brain. A comparison of
      established neuroinflammatory parameters such as white matter rarefactions,
      development of cytotoxic edema, astrogliosis, loss of oligodendrocytes, and major
      cytokines levels in wild type and knockout mice suggested that the
      neuroinflammatory response in SphK1-/- mice was significantly upregulated. At 6
      hours after intracerebroventricular injection of LPS in SphK1-/- mice, the
      immunoreactivity of the microglia markers and astrocyte marker glial fibrillary
      acidic protein (GFAP) were significantly increased, while the oligodendrocyte
      marker O4 was decreased compared to WT mice. Furthermore, western blotting data
      showed increased levels of GFAP. These results suggest that SphK1 activation is
      involved in the regulation of LPS induced brain injury. RESEARCH HIGHLIGHTS: *
      Lipopolysaccharide (LPS) intracerebral injection induces severe
      neuroinflammation. * Sphingosine kinase 1 deletion worsens the effect of the LPS.
      * Overexpression of SphK1 might be a potential new treatment approach to
      neuroinflammation.

PMID- 22615771
TI  - MiR-200c regulates Noxa expression and sensitivity to proteasomal inhibitors.
AB  - The pro-apoptotic p53 target Noxa is a BH3-only protein that antagonizes the
      function of selected anti-apoptotic Bcl-2 family members. While much is known
      regarding the transcriptional regulation of Noxa, its posttranscriptional
      regulation remains relatively unstudied. In this study, we therefore investigated
      whether Noxa is regulated by microRNAs. Using a screen combining luciferase
      reporters, bioinformatic target prediction analysis and microRNA expression
      profiling, we identified miR-200c as a negative regulator of Noxa expression. MiR
      200c was shown to repress basal expression of Noxa, as well as Noxa expression
      induced by various stimuli, including proteasomal inhibition. Luciferase reporter
      experiments furthermore defined one miR-200c target site in the Noxa 3'UTR that
      is essential for this direct regulation. In spite of the miR-200c:Noxa
      interaction, miR-200c overexpression led to increased sensitivity to the
      clinically used proteasomal inhibitor bortezomib in several cell lines. This
      apparently contradictory finding was reconciled by the fact that in cells devoid
      of Noxa expression, miR-200c overexpression had an even more pronounced positive
      effect on apoptosis induced by proteasomal inhibition. Together, our data define
      miR-200c as a potentiator of bortezomib-induced cell death. At the same time, we
      show that miR-200c is a novel negative regulator of the pro-apoptotic Bcl-2
      family member Noxa.

PMID- 22615772
TI  - Coccidian infection causes oxidative damage in greenfinches.
AB  - The main tenet of immunoecology is that individual variation in immune
      responsiveness is caused by the costs of immune responses to the hosts. Oxidative
      damage resulting from the excessive production of reactive oxygen species during
      immune response is hypothesized to form one of such costs. We tested this
      hypothesis in experimental coccidian infection model in greenfinches Carduelis
      chloris. Administration of isosporan coccidians to experimental birds did not
      affect indices of antioxidant protection (TAC and OXY), plasma triglyceride and
      carotenoid levels or body mass, indicating that pathological consequences of
      infection were generally mild. Infected birds had on average 8% higher levels of
      plasma malondialdehyde (MDA, a toxic end-product of lipid peroxidation) than un
      infected birds. The birds that had highest MDA levels subsequent to experimental
      infection experienced the highest decrease in infection intensity. This
      observation is consistent with the idea that oxidative stress is a causative
      agent in the control of coccidiosis and supports the concept of oxidative costs
      of immune responses and parasite resistance. The finding that oxidative damage
      accompanies even the mild infection with a common parasite highlights the
      relevance of oxidative stress biology for the immunoecological research.

PMID- 22615773
TI  - Evolution of Burkholderia pseudomallei in recurrent melioidosis.
AB  - Burkholderia pseudomallei, the etiologic agent of human melioidosis, is capable
      of causing severe acute infection with overwhelming septicemia leading to death.
      A high rate of recurrent disease occurs in adult patients, most often due to
      recrudescence of the initial infecting strain. Pathogen persistence and evolution
      during such relapsing infections are not well understood. Bacterial cells present
      in the primary inoculum and in late infections may differ greatly, as has been
      observed in chronic disease, or they may be genetically similar. To test these
      alternative models, we conducted whole-genome comparisons of clonal primary and
      relapse B. pseudomallei isolates recovered six months to six years apart from
      four adult Thai patients. We found differences within each of the four pairs, and
      some, including a 330 Kb deletion, affected substantial portions of the genome.
      Many of the changes were associated with increased antibiotic resistance. We also
      found evidence of positive selection for deleterious mutations in a TetR family
      transcriptional regulator from a set of 107 additional B. pseudomallei strains.
      As part of the study, we sequenced to base-pair accuracy the genome of B.
      pseudomallei strain 1026b, the model used for genetic studies of B. pseudomallei
      pathogenesis and antibiotic resistance. Our findings provide new insights into
      pathogen evolution during long-term infections and have important implications
      for the development of intervention strategies to combat recurrent melioidosis.

PMID- 22615775
TI  - Misperceptions in the trajectories of objects undergoing curvilinear motion.
AB  - Trajectory perception is crucial in scene understanding and action. A variety of
      trajectory misperceptions have been reported in the literature. In this study, we
      quantify earlier observations that reported distortions in the perceived shape of
      bilinear trajectories and in the perceived positions of their deviation. Our
      results show that bilinear trajectories with deviation angles smaller than 90 deg
      are perceived smoothed while those with deviation angles larger than 90 degrees
      are perceived sharpened. The sharpening effect is weaker in magnitude than the
      smoothing effect. We also found a correlation between the distortion of perceived
      trajectories and the perceived shift of their deviation point. Finally, using a
      dual-task paradigm, we found that reducing attentional resources allocated to the
      moving target causes an increase in the perceived shift of the deviation point of
      the trajectory. We interpret these results in the context of interactions between
      motion and position systems.

PMID- 22615774
TI  - Prefrontal neural activity when feedback is not relevant to adjust performance.
AB  - It has been shown that the rostral cingulate zone (RCZ) in humans uses both
      positive and negative feedback to evaluate performance and to flexibly adjust
      behaviour. Less is known on how the feedback types are processed by the RCZ and
      other prefrontal brain areas, when feedback can only be used to evaluate
      performance, but cannot be used to adjust behaviour. The present fMRI study aimed
      at investigating feedback that can only be used to evaluate performance in a word
      learning paradigm. One group of volunteers (N = 17) received informative,
      performance-dependent positive or negative feedback after each trial. Since new
      words had to be learnt in each trial, the feedback could not be used for task
      specific adaptations. The other group (N = 17) always received non-informative
      feedback, providing neither information about performance nor about possible task
      specific adaptations. Effects of the informational value of feedback were
      assessed between-subjects, comparing trials with positive and negative
      informative feedback to non-informative feedback. Effects of feedback valence
      were assessed by comparing neural activity to positive and negative feedback
      within the informative-feedback group. Our results show that several prefrontal
      regions, including the pre-SMA, the inferior frontal cortex and the insula were
      sensitive to both, the informational value and the valence aspect of the feedback
      with stronger activations to informative as compared to non-informative feedback
      and to informative negative compared to informative positive feedback. The only
      exception was RCZ which was sensitive to the informational value of the feedback,
      but not to feedback valence. The findings indicate that outcome information per
      se is sufficient to activate prefrontal brain regions, with the RCZ being the
      only prefrontal brain region which is equally sensitive to positive and negative
      feedback.

PMID- 22615776
TI  - Recovery in Borderline Personality Disorder (BPD): a qualitative study of service
      users' perspectives.
AB  - BACKGROUND: Symptom improvement in Borderline Personality Disorder (BPD) is more
      common than previously hypothesised. However, it remains unclear whether it
      reflects service users' personal goals of recovery. The present study aimed to
      explore what service users with BPD view as recovery. METHODS: 48 service users
      were recruited from secondary mental health services and their views on their
      personal goals and the meaning of recovery were explored in in-depth semi
      structured interviews. The study drew on grounded theory and thematic analysis.
      RESULTS: Service users believed that recovery involved developing self-acceptance
      and self-confidence, gaining control over emotions, improving relationships,
      employment, and making progress in symptoms like suicidality and self-harming.
      They felt that psychotherapies for BPD often had an extreme focus on specific
      areas, like self-harming or relationships, and that some of their goals were
      neglected. Although full recovery was seen as a distant goal, interviewees felt
      that they could learn how to deal with their problems in more effective ways and
      make meaningful progress in their lives. CONCLUSIONS: Specialist therapies for
      BPD explicitly address some of the recovery goals that are important to service
      users, whereas other goals are only indirectly or poorly addressed. Professionals
      might need to work with service users towards devising comprehensive
      individualised case formulations, including all treatment targets that are
      important to service users, their priorities, and long-term plans on how their
      targets might be met and which services might be involved.

PMID- 22615777
TI  - Mechanism of nucleic acid unwinding by SARS-CoV helicase.
AB  - The non-structural protein 13 (nsp13) of Severe Acute Respiratory Syndrome
      Coronavirus (SARS-CoV) is a helicase that separates double-stranded RNA (dsRNA)
      or DNA (dsDNA) with a 5' -> 3' polarity, using the energy of nucleotide
      hydrolysis. We determined the minimal mechanism of helicase function by nsp13. We
      showed a clear unwinding lag with increasing length of the double-stranded region
      of the nucleic acid, suggesting the presence of intermediates in the unwinding
      process. To elucidate the nature of the intermediates we carried out transient
      kinetic analysis of the nsp13 helicase activity. We demonstrated that the enzyme
      unwinds nucleic acid in discrete steps of 9.3 base-pairs (bp) each, with a
      catalytic rate of 30 steps per second. Therefore the net unwinding rate is ~280
      base-pairs per second. We also showed that nsp12, the SARS-CoV RNA-dependent RNA
      polymerase (RdRp), enhances (2-fold) the catalytic efficiency of nsp13 by
      increasing the step size of nucleic acid (RNA/RNA or DNA/DNA) unwinding. This
      effect is specific for SARS-CoV nsp12, as no change in nsp13 activity was
      observed when foot-and-mouth-disease virus RdRp was used in place of nsp12. Our
      data provide experimental evidence that nsp13 and nsp12 can function in a
      concerted manner to improve the efficiency of viral replication and enhance our
      understanding of nsp13 function during SARS-CoV RNA synthesis.

PMID- 22615778
TI  - Algebraic comparison of partial lists in bioinformatics.
AB  - The outcome of a functional genomics pipeline is usually a partial list of
      genomic features, ranked by their relevance in modelling biological phenotype in
      terms of a classification or regression model. Due to resampling protocols or to
      a meta-analysis comparison, it is often the case that sets of alternative feature
      lists (possibly of different lengths) are obtained, instead of just one list.
      Here we introduce a method, based on permutations, for studying the variability
      between lists ("list stability") in the case of lists of unequal length. We
      provide algorithms evaluating stability for lists embedded in the full feature
      set or just limited to the features occurring in the partial lists. The method is
      demonstrated by finding and comparing gene profiles on a large prostate cancer
      dataset, consisting of two cohorts of patients from different countries, for a
      total of 455 samples.

PMID- 22615779
TI  - K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen
      including d4T or AZT: comparison of Sanger and UDP sequencing data.
AB  - BACKGROUND: We and others have shown that subtype C HIV-1 isolates from patients
      failing on a regimen containing stavudine (d4T) or zidovudine (AZT) exhibit
      thymidine-associated mutations (TAMs) and K65R which can impair the efficacy of
      Tenofovir (TDF) at second line. Depending on the various studies, the prevalence
      of K65R substitution as determined by the Sanger method ranges from 4 to 30%. Our
      aim was to determine whether ultra-deep pyrosequencing (UDPS) could provide more
      information than the Sanger method about selection of K65R in this population of
      patients. METHODS: 27 subtype C HIV-1 isolates from treated patients failing on a
      regimen with d4T or AZT plus lamivudine (3TC) plus nevirapine (NVP) or efavirenz
      (EFV) and who had been sequenced by Sanger were investigated by UDPS at codon 65
      of the reverse transcriptase (RT). 18 isolates from naive patients and dilutions
      of a control K65R plasmid were analysed by Sanger plus UDPS. RESULTS: Analysis of
      Sanger sequences of subtype C HIV-1 isolates from naive patients exhibited
      expected polymorphic substitutions compared to subtype B but no drug resistance
      mutations (DRMs). Quantitation of K65R variants by UDPS ranged from <0.4% to
      3.08%. Sanger sequences of viral isolates from patients at failure of d4T or AZT
      plus 3TC plus NVP or EFV showed numerous DRMs to nucleoside reverse transcriptase
      inhibitors (NRTIs) including M184V, thymidine-associated mutations (TAMs) plus
      DRMs to non- nucleoside reverse transcriptase inhibitors (NNRTIs). Two K65R were
      observed by Sanger in this series of 27 samples with UDPS percentages of 27 and
      87%. Other samples without K65R by Sanger exhibited quantities of K65R variants
      ranging from <0.4% to 0.80%, which were below the values observed in isolates
      from naive patients. CONCLUSIONS: While Sanger sequencing of subtype C isolates
      from treated patients at failure of d4T or AZT plus 3TC plus NVP or EFV exhibited
      numerous mutations including TAMs and 8% K65R, UDPS quantitation of K65R variants
      in the same series did not provide any more information than Sanger.

PMID- 22615781
TI  - Candidate gene-based association study of antipsychotic-induced movement
      disorders in long-stay psychiatric patients: a prospective study.
AB  - OBJECTIVE: Four types of antipsychotic-induced movement disorders: tardive
      dyskinesia (TD), parkinsonism, akathisia and tardive dystonia, subtypes of TD
      (orofacial and limb truncal dyskinesia), subtypes of parkinsonism (rest tremor,
      rigidity, and bradykinesia), as well as a principal-factor of the movement
      disorders and their subtypes, were examined for association with variation in 10
      candidate genes (PPP1R1B, BDNF, DRD3, DRD2, HTR2A, HTR2C, COMT, MnSOD, CYP1A2,
      and RGS2). METHODS: Naturalistic study of 168 white long-stay patients with
      chronic mental illness requiring long-term antipsychotic treatment, examined by
      the same rater at least two times over a 4-year period, with a mean follow-up
      time of 1.1 years, with validated scales for TD, parkinsonism, akathisia, and
      tardive dystonia. The authors genotyped 31 SNPs, associated with movement
      disorders or schizophrenia in previous studies. Genotype and allele frequency
      comparisons were performed with multiple regression methods for continuous
      movement disorders. RESULTS: VARIOUS SNPS REACHED NOMINAL SIGNIFICANCE: TD and
      orofacial dyskinesia with rs6265 and rs988748, limb truncal dyskinesia with
      rs6314, rest tremor with rs6275, rigidity with rs6265 and rs4680, bradykinesia
      with rs4795390, akathisia with rs4680, tardive dystonia with rs1799732, rs4880
      and rs1152746. After controlling for multiple testing, no significant results
      remained. CONCLUSIONS: The findings suggest that selected SNPs are not associated
      with a susceptibility to movement disorders. However, as the sample size was
      small and previous studies show inconsistent results, definite conclusions cannot
      be made. Replication is needed in larger study samples, preferably in
      longitudinal studies which take the fluctuating course of movement disorders and
      gene-environment interactions into account.

PMID- 22615780
TI  - Novel role for the innate immune receptor Toll-like receptor 4 (TLR4) in the
      regulation of the Wnt signaling pathway and photoreceptor apoptosis.
AB  - Recent evidence has implicated innate immunity in regulating neuronal survival in
      the brain during stroke and other neurodegenerations. Photoreceptors are
      specialized light-detecting neurons in the retina that are essential for vision.
      In this study, we investigated the role of the innate immunity receptor TLR4 in
      photoreceptors. TLR4 activation by lipopolysaccharide (LPS) significantly reduced
      the survival of cultured mouse photoreceptors exposed to oxidative stress. With
      respect to mechanism, TLR4 suppressed Wnt signaling, decreased phosphorylation
      and activation of the Wnt receptor LRP6, and blocked the protective effect of the
      Wnt3a ligand. Paradoxically, TLR4 activation prior to oxidative injury protected
      photoreceptors, in a phenomenon known as preconditioning. Expression of TNFalpha
      and its receptors TNFR1 and TNFR2 decreased during preconditioning, and
      preconditioning was mimicked by TNFalpha antagonists, but was independent of Wnt
      signaling. Therefore, TLR4 is a novel regulator of photoreceptor survival that
      acts through the Wnt and TNFalpha pathways.

PMID- 22615782
TI  - Residency and spatial use by reef sharks of an isolated seamount and its
      implications for conservation.
AB  - Although marine protected areas (MPAs) are a common conservation strategy, these
      areas are often designed with little prior knowledge of the spatial behaviour of
      the species they are designed to protect. Currently, the Coral Sea area and its
      seamounts (north-east Australia) are under review to determine if MPAs are
      warranted. The protection of sharks at these seamounts should be an integral
      component of conservation plans. Therefore, knowledge on the spatial ecology of
      sharks at the Coral Sea seamounts is essential for the appropriate implementation
      of management and conservation plans. Acoustic telemetry was used to determine
      residency, site fidelity and spatial use of three shark species at Osprey Reef:
      whitetip reef sharks Triaenodon obesus, grey reef sharks Carcharhinus
      amblyrhynchos and silvertip sharks Carcharhinus albimarginatus. Most individuals
      showed year round residency at Osprey Reef, although five of the 49 individuals
      tagged moved to the neighbouring Shark Reef (~14 km away) and one grey reef shark
      completed a round trip of ~250 km to the Great Barrier Reef. Additionally,
      individuals of white tip and grey reef sharks showed strong site fidelity to the
      areas they were tagged, and there was low spatial overlap between groups of
      sharks tagged at different locations. Spatial use at Osprey Reef by adult sharks
      is generally restricted to the north-west corner. The high residency and limited
      spatial use of Osprey Reef suggests that reef sharks would be highly vulnerable
      to targeted fishing pressure and that MPAs incorporating no-take of sharks would
      be effective in protecting reef shark populations at Osprey and Shark Reef.

PMID- 22615783
TI  - High LRRK2 levels fail to induce or exacerbate neuronal alpha-synucleinopathy in
      mouse brain.
AB  - The G2019S mutation in the multidomain protein leucine-rich repeat kinase 2
      (LRRK2) is one of the most frequently identified genetic causes of Parkinson's
      disease (PD). Clinically, LRRK2(G2019S) carriers with PD and idiopathic PD
      patients have a very similar disease with brainstem and cortical Lewy pathology
      (alpha-synucleinopathy) as histopathological hallmarks. Some patients have Tau
      pathology. Enhanced kinase function of the LRRK2(G2019S) mutant protein is a
      prime suspect mechanism for carriers to develop PD but observations in LRRK2
      knock-out, G2019S knock-in and kinase-dead mutant mice suggest that LRRK2 steady
      state abundance of the protein also plays a determining role. One critical
      question concerning the molecular pathogenesis in LRRK2(G2019S) PD patients is
      whether alpha-synuclein (aSN) has a contributory role. To this end we generated
      mice with high expression of either wildtype or G2019S mutant LRRK2 in brainstem
      and cortical neurons. High levels of these LRRK2 variants left endogenous aSN and
      Tau levels unaltered and did not exacerbate or otherwise modify alpha
      synucleinopathy in mice that co-expressed high levels of LRRK2 and aSN in brain
      neurons. On the contrary, in some lines high LRRK2 levels improved motor skills
      in the presence and absence of aSN-transgene-induced disease. Therefore, in many
      neurons high LRRK2 levels are well tolerated and not sufficient to drive or
      exacerbate neuronal alpha-synucleinopathy.

PMID- 22615784
TI  - An osmotic model of the growing pollen tube.
AB  - Pollen tube growth is central to the sexual reproduction of plants and is a
      longstanding model for cellular tip growth. For rapid tip growth, cell wall
      deposition and hardening must balance the rate of osmotic water uptake, and this
      involves the control of turgor pressure. Pressure contributes directly to both
      the driving force for water entry and tip expansion causing thinning of wall
      material. Understanding tip growth requires an analysis of the coordination of
      these processes and their regulation. Here we develop a quantitative
      physiological model which includes water entry by osmosis, the incorporation of
      cell wall material and the spreading of that material as a film at the tip.
      Parameters of the model have been determined from the literature and from
      measurements, by light, confocal and electron microscopy, together with results
      from experiments made on dye entry and plasmolysis in Lilium longiflorum. The
      model yields values of variables such as osmotic and turgor pressure, growth
      rates and wall thickness. The model and its predictive capacity were tested by
      comparing programmed simulations with experimental observations following
      perturbations of the growth medium. The model explains the role of turgor
      pressure and its observed constancy during oscillations; the stability of wall
      thickness under different conditions, without which the cell would burst; and
      some surprising properties such as the need for restricting osmotic permeability
      to a constant area near the tip, which was experimentally confirmed. To achieve
      both constancy of pressure and wall thickness under the range of conditions
      observed in steady-state growth the model reveals the need for a sensor that
      detects the driving potential for water entry and controls the deposition rate of
      wall material at the tip.

PMID- 22615785
TI  - Identification of genes related to white and black plumage formation by RNA-Seq
      from white and black feather bulbs in ducks.
AB  - To elucidate the genes involved in the formation of white and black plumage in
      ducks, RNA from white and black feather bulbs of an F(2) population were analyzed
      using RNA-Seq. A total of 2,642 expressed sequence tags showed significant
      differential expression between white and black feather bulbs. Among these tags,
      186 matched 133 annotated genes that grouped into 94 pathways. A number of genes
      controlling melanogenesis showed differential expression between the two types of
      feather bulbs. This differential expression was confirmed by qPCR analysis and
      demonstrated that Tyr (Tyrosinase) and Tyrp1 (Tyrosinase-related protein-1) were
      expressed not in W-W (white feather bulb from white dorsal plumage) and W-WB
      (white feather bulb from white-black dorsal plumage) but in B-B (black feather
      bulb from black dorsal plumage) and B-WB (black feather bulb from white-black
      dorsal plumage) feather bulbs. Tyrp2 (Tyrosinase-related protein-2) gene did not
      show expression in the four types of feather bulbs but expressed in retina. C-kit
      (The tyrosine kinase receptor) expressed in all of the samples but the relative
      mRNA expression in B-B or B-WB was approximately 10 fold higher than that in W-W
      or W-WB. Additionally, only one of the two Mitf isoforms was associated with
      plumage color determination. Downregulation of c-Kit and Mitf in feather bulbs
      may be the cause of white plumage in the duck.

PMID- 22615786
TI  - Do natural proteins differ from random sequences polypeptides? Natural vs. random
      proteins classification using an evolutionary neural network.
AB  - Are extant proteins the exquisite result of natural selection or are they random
      sequences slightly edited by evolution? This question has puzzled biochemists for
      long time and several groups have addressed this issue comparing natural protein
      sequences to completely random ones coming to contradicting conclusions. Previous
      works in literature focused on the analysis of primary structure in an attempt to
      identify possible signature of evolutionary editing. Conversely, in this work we
      compare a set of 762 natural proteins with an average length of 70 amino acids
      and an equal number of completely random ones of comparable length on the basis
      of their structural features. We use an ad hoc Evolutionary Neural Network
      Algorithm (ENNA) in order to assess whether and to what extent natural proteins
      are edited from random polypeptides employing 11 different structure-related
      variables (i.e. net charge, volume, surface area, coil, alpha helix, beta sheet,
      percentage of coil, percentage of alpha helix, percentage of beta sheet,
      percentage of secondary structure and surface hydrophobicity). The ENNA algorithm
      is capable to correctly distinguish natural proteins from random ones with an
      accuracy of 94.36%. Furthermore, we study the structural features of 32 random
      polypeptides misclassified as natural ones to unveil any structural similarity to
      natural proteins. Results show that random proteins misclassified by the ENNA
      algorithm exhibit a significant fold similarity to portions or subdomains of
      extant proteins at atomic resolution. Altogether, our results suggest that
      natural proteins are significantly edited from random polypeptides and
      evolutionary editing can be readily detected analyzing structural features.
      Furthermore, we also show that the ENNA, employing simple structural descriptors,
      can predict whether a protein chain is natural or random.

PMID- 22615787
TI  - Acupuncture for the treatment of dry eye: a multicenter randomised controlled
      trial with active comparison intervention (artificial teardrops).
AB  - PURPOSE: To evaluate the effects of acupuncture compared to a control group using
      artificial tears. METHODS:  SETTING & DESIGN: multicenter randomised controlled
      trial (three local research hospitals of South Korea). STUDY POPULATION: 150
      patients with moderate to severe dry eye. INTERVENTION: Participants were
      randomly allocated into four weeks of acupuncture treatment (bilateral BL2, GB14,
      TE 23, Ex1, ST1, GB20, LI4, LI11 and single GV23) or to the artificial tears
      group (sodium carboxymethylcellulose). MAIN OUTCOME MEASURE(S): The ocular
      surface disease index (OSDI), tear film break-up time (TFBUT), Schirmer Iota
      test, visual analogue scale (VAS) for self-assessment of ocular discomfort,
      general assessment (by both acupuncture practitioners and participants) and
      quality of life (QOL) through the Measure Yourself Medical Outcome Profile-2
      (MYMOP-2). RESULTS: There was no statistically significant difference between two
      groups for the improvement of dry eye symptoms as measured by OSDI (MD -16.11,
      95% CI [-20.91, -11.32] with acupuncture and -15.37, 95% CI [-19.57, -11.16] with
      artificial tears; P = 0.419), VAS (acupuncture: -23.84 [-29.59, -18.09];
      artificial tears: -22.2 [-27.24, -17.16], P = 0.530) or quality of life
      (acupuncture: -1.32 [-1.65, -0.99]; artificial tears: -0.96 [-1.32, -0.6], P =
      0.42) immediately after treatment. However, compared with artificial tears group,
      the OSDI (acupuncture: -16.15 [-21.38, -10.92]; artificial tears: -10.76 [-15.25,
      -6.27], P = 0.030) and VAS (acupuncture: -23.88 [-30.9, -16.86]; artificial
      tears: -14.71 [-20.86, -8.55], P = 0.018) were significantly improved in the
      acupuncture group at 8 weeks after the end of acupuncture treatment. TFBUT
      measurements increased significantly in the acupuncture group after treatment.
      CONCLUSIONS: Acupuncture may have benefits on the mid-term outcomes related to
      dry eye syndrome compared with artificial tears. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01105221.

PMID- 22615788
TI  - Normal leptin expression, lower adipogenic ability, decreased leptin receptor and
      hyposensitivity to Leptin in Adolescent Idiopathic Scoliosis.
AB  - Leptin has been suggested to play a role in the etiology of Adolescent Idiopathic
      Scoliosis (AIS), however, the leptin levels in AIS girls are still a discrepancy,
      and no in vitro study of leptin in AIS is reported. We took a series of case
      control studies, trying to understand whether Leptin gene polymorphisms are
      involved in the etiology of the AIS or the change in leptin level is a secondary
      event, to assess the level of leptin receptor, and to evaluate the differences of
      response to leptin between AIS cases and controls. We screened all exons of
      Leptin gene in 45 cases and 45 controls and selected six tag SNPs to cover all
      the observed variations. Association analysis in 446 AIS patients and 550 healthy
      controls showed no association between the polymorphisms of Leptin gene and
      susceptibility/severity to AIS. Moreover, adipogenesis assay of bone mesenchymal
      stem cells (MSCs) suggested that the adipogenic ability of MSCs from AIS girls
      was lower than controls. After adjusting the differentiation rate, expressions of
      leptin and leptin receptor were similar between two groups. Meanwhile,
      osteogenesis assay of MSC showed the leptin level was similar after adjusting the
      differentiation rate, but the leptin receptor level was decreased in induced AIS
      osteoblasts. Immunocytochemistry and western blot analysis showed less leptin
      receptors expressed in AIS group. Furthermore, factorial designed studies with
      adipogenesis and osteogenesis revealed that the MSCs from patients have no
      response to leptin treatment. Our results suggested that Leptin gene variations
      are not associated with AIS and low serum leptin probably is a secondary outcome
      which may be related to the low capability of adipogenesis in AIS. The decreased
      leptin receptor levels may lead to the hyposensitivity to leptin. These findings
      implied that abnormal peripheral leptin signaling plays an important role in the
      pathological mechanism of AIS.

PMID- 22615789
TI  - Drugs of last resort? The use of polymyxins and tigecycline at US Veterans
      Affairs medical centers, 2005-2010.
AB  - Multidrug-resistant (MDR) and carbapenem-resistant (CR) Gram-negative pathogens
      are becoming increasingly prevalent around the globe. Polymyxins and tigecycline
      are among the few antibiotics available to treat infections with these bacteria
      but little is known about the frequency of their use. We therefore aimed to
      estimate the parenteral use of these two drugs in Veterans Affairs medical
      centers (VAMCs) and to describe the pathogens associated with their
      administration. For this purpose we retrospectively analyzed barcode medication
      administration data of parenteral administrations of polymyxins and tigecycline
      in 127 acute-care VAMCs between October 2005 and September 2010. Overall,
      polymyxin and tigecycline use were relatively low at 0.8 days of therapy
      (DOT)/1000 patient days (PD) and 1.6 DOT/1000PD, respectively. Use varied widely
      across facilities, but increased overall during the study period. Eight
      facilities accounted for three-quarters of all polymyxin use. The same statistic
      for tigecycline use was twenty-six VAMCs. There were 1,081 MDR or CR isolates
      during 747 hospitalizations associated with polymyxin use (1.4/hospitalization).
      For tigecycline these number were slightly lower: 671 MDR or CR isolates during
      500 hospitalizations (1.3/hospitalization) (p = 0.06). An ecological correlation
      between the two antibiotics and combined CR and MDR Gram-negative isolates per
      1000PD during the study period was also observed (Pearson's correlation
      coefficient r = 0.55 polymyxin, r = 0.19 tigecycline). In summary, while
      polymyxin and tigecycline use is low in most VAMCs, there has been an increase
      over the study period. Polymyxin use in particular is associated with the
      presence of MDR Gram-negative pathogens and may be useful as a surveillance
      measure in the future.

PMID- 22615790
TI  - Kinematic plasticity during flight in fruit bats: individual variability in
      response to loading.
AB  - All bats experience daily and seasonal fluctuation in body mass. An increase in
      mass requires changes in flight kinematics to produce the extra lift necessary to
      compensate for increased weight. How bats modify their kinematics to increase
      lift, however, is not well understood. In this study, we investigated the effect
      of a 20% increase in mass on flight kinematics for Cynopterus brachyotis, the
      lesser dog-faced fruit bat. We reconstructed the 3D wing kinematics and how they
      changed with the additional mass. Bats showed a marked change in wing kinematics
      in response to loading, but changes varied among individuals. Each bat adjusted a
      different combination of kinematic parameters to increase lift, indicating that
      aerodynamic force generation can be modulated in multiple ways. Two main
      kinematic strategies were distinguished: bats either changed the motion of the
      wings by primarily increasing wingbeat frequency, or changed the configuration of
      the wings by increasing wing area and camber. The complex, individual-dependent
      response to increased loading in our bats points to an underappreciated aspect of
      locomotor control, in which the inherent complexity of the biomechanical system
      allows for kinematic plasticity. The kinematic plasticity and functional
      redundancy observed in bat flight can have evolutionary consequences, such as an
      increase potential for morphological and kinematic diversification due to
      weakened locomotor trade-offs.

PMID- 22615791
TI  - Genetic diversity of the genus Cosavirus in the family Picornaviridae: a new
      species, recombination, and 26 new genotypes.
AB  - The proposed viral genus human Cosavirus (HCoSV) consists of diverse
      picornaviruses found at high prevalence in the feces of children from developing
      countries. We sequenced four near-full length genomes and 45 partial VP1 region
      from HCoSV in human feces from healthy children and children with acute flaccid
      paralysis in Pakistan, Nigeria and Tunisia and from healthy and diarrhetic adults
      in Nepal. Genetic analyses of the near-full length genomes revealed presence of a
      new candidate cosavirus species provisionally labelled as species F (HCoSV-F). A
      HCoSV genome showed evidence of recombination between species D and E viruses at
      the P1/P2 junction indicating that these viruses may be reclassified as a single
      highly diverse species. Based on genetic distance criteria for assigning
      genotypes corresponding to neutralization serotypes in enteroviruses we
      identified 26 new HCoSV genotypes belonging to species A, D, and E. The detection
      of a large number of HCoSV genotypes based on still limited geographic sampling
      indicates that the phenotypic effects of cosaviruses on infected subjects are
      likely to be as highly diverse as those of human enteroviruses.

PMID- 22615792
TI  - Development and validation of an automated high-throughput system for zebrafish
      in vivo screenings.
AB  - The zebrafish is a vertebrate model compatible with the paradigms of drug
      discovery. The small size and transparency of zebrafish embryos make them
      amenable for the automation necessary in high-throughput screenings. We have
      developed an automated high-throughput platform for in vivo chemical screenings
      on zebrafish embryos that includes automated methods for embryo dispensation,
      compound delivery, incubation, imaging and analysis of the results. At present,
      two different assays to detect cardiotoxic compounds and angiogenesis inhibitors
      can be automatically run in the platform, showing the versatility of the system.
      A validation of these two assays with known positive and negative compounds, as
      well as a screening for the detection of unknown anti-angiogenic compounds, have
      been successfully carried out in the system developed. We present a totally
      automated platform that allows for high-throughput screenings in a vertebrate
      organism.

PMID- 22615793
TI  - Investigation of host candidate malaria-associated risk/protective SNPs in a
      Brazilian Amazonian population.
AB  - The Brazilian Amazon is a hypo-endemic malaria region with nearly 300,000 cases
      each year. A variety of genetic polymorphisms, particularly in erythrocyte
      receptors and immune response related genes, have been described to be associated
      with susceptibility and resistance to malaria. In order to identify polymorphisms
      that might be associated with malaria clinical outcomes in a Brazilian Amazonian
      population, sixty-four human single nucleotide polymorphisms in 37 genes were
      analyzed using a Sequenom massARRAY iPLEX platform. A total of 648 individuals
      from two malaria endemic areas were studied, including 535 malaria cases (113
      individuals with clinical mild malaria, 122 individuals with asymptomatic
      infection and 300 individuals with history of previous mild malaria) and 113
      health controls with no history of malaria. The data revealed significant
      associations (p<0.003) between one SNP in the IL10 gene (rs1800896) and one SNP
      in the TLR4 gene (rs4986790) with reduced risk for clinical malaria, one SNP in
      the IRF1 gene (rs2706384) with increased risk for clinical malaria, one SNP in
      the LTA gene (rs909253) with protection from clinical malaria and one SNP in the
      TNF gene (RS1800750) associated with susceptibility to clinical malaria. Also, a
      new association was found between a SNP in the CTL4 gene (rs2242665), located at
      the major histocompatibility complex III region, and reduced risk for clinical
      malaria. This study represents the first association study from an Amazonian
      population involving a large number of host genetic polymorphisms with
      susceptibility or resistance to Plasmodium infection and malaria outcomes.
      Further studies should include a larger number of individuals, refined parameters
      and a fine-scale map obtained through DNA sequencing to increase the knowledge of
      the Amazonian population genetic diversity.

PMID- 22615794
TI  - Stable gene targeting in human cells using single-strand oligonucleotides with
      modified bases.
AB  - Recent advances allow multiplexed genome engineering in E. coli, employing easily
      designed oligonucleotides to edit multiple loci simultaneously. A similar
      technology in human cells would greatly expedite functional genomics, both by
      enhancing our ability to test how individual variants such as single nucleotide
      polymorphisms (SNPs) are related to specific phenotypes, and potentially allowing
      simultaneous mutation of multiple loci. However, oligo-mediated targeting of
      human cells is currently limited by low targeting efficiencies and low survival
      of modified cells. Using a HeLa-based EGFP-rescue reporter system we show that
      use of modified base analogs can increase targeting efficiency, in part by
      avoiding the mismatch repair machinery. We investigate the effects of
      oligonucleotide toxicity and find a strong correlation between the number of
      phosphorothioate bonds and toxicity. Stably EGFP-corrected cells were generated
      at a frequency of ~0.05% with an optimized oligonucleotide design combining
      modified bases and reduced number of phosphorothioate bonds. We provide evidence
      from comparative RNA-seq analysis suggesting cellular immunity induced by the
      oligonucleotides might contribute to the low viability of oligo-corrected cells.
      Further optimization of this method should allow rapid and scalable genome
      engineering in human cells.

PMID- 22615795
TI  - A primary survey on bryophyte species reveals two novel classes of nucleotide
      binding site (NBS) genes.
AB  - Due to their potential roles in pathogen defense, genes encoding nucleotide
      binding site (NBS) domain have been particularly surveyed in many angiosperm
      genomes. Two typical classes were found: one is the TIR-NBS-LRR (TNL) class and
      the other is the CC-NBS-LRR (CNL) class. It is seldom known, however, what kind
      of NBS-encoding genes are mainly present in other plant groups, especially the
      most ancient groups of land plants, that is, bryophytes. To fill this gap of
      knowledge, in this study, we mainly focused on two bryophyte species: the moss
      Physcomitrella patens and the liverwort Marchantia polymorpha, to survey their
      NBS-encoding genes. Surprisingly, two novel classes of NBS-encoding genes were
      discovered. The first novel class is identified from the P. patens genome and a
      typical member of this class has a protein kinase (PK) domain at the N-terminus
      and a LRR domain at the C-terminus, forming a complete structure of PK-NBS-LRR
      (PNL), reminiscent of TNL and CNL classes in angiosperms. The second class is
      found from the liverwort genome and a typical member of this class possesses an
      alpha/beta-hydrolase domain at the N-terminus and also a LRR domain at the C
      terminus (Hydrolase-NBS-LRR, HNL). Analysis on intron positions and phases also
      confirmed the novelty of HNL and PNL classes, as reflected by their specific
      intron locations or phase characteristics. Phylogenetic analysis covering all
      four classes of NBS-encoding genes revealed a closer relationship among the HNL,
      PNL and TNL classes, suggesting the CNL class having a more divergent status from
      the others. The presence of specific introns highlights the chimerical structures
      of HNL, PNL and TNL genes, and implies their possible origin via exon-shuffling
      during the quick lineage separation processes of early land plants.

PMID- 22615796
TI  - Interaction between coastal and oceanic ecosystems of the Western and Central
      Pacific Ocean through predator-prey relationship studies.
AB  - The Western and Central Pacific Ocean sustains the highest tuna production in the
      world. This province is also characterized by many islands and a complex
      bathymetry that induces specific current circulation patterns with the potential
      to create a high degree of interaction between coastal and oceanic ecosystems.
      Based on a large dataset of oceanic predator stomach contents, our study used
      generalized linear models to explore the coastal-oceanic system interaction by
      analyzing predator-prey relationship. We show that reef organisms are a frequent
      prey of oceanic predators. Predator species such as albacore (Thunnus alalunga)
      and yellowfin tuna (Thunnus albacares) frequently consume reef prey with higher
      probability of consumption closer to land and in the western part of the Pacific
      Ocean. For surface-caught-predators consuming reef prey, this prey type
      represents about one third of the diet of predators smaller than 50 cm. The
      proportion decreases with increasing fish size. For predators caught at depth and
      consuming reef prey, the proportion varies with predator species but generally
      represents less than 10%. The annual consumption of reef prey by the yellowfin
      tuna population was estimated at 0.8 +/- 0.40 CV million tonnes or 2.17 *
      10(12)+/- 0.40 CV individuals. This represents 6.1% +/- 0.17 CV in weight of
      their diet. Our analyses identify some of the patterns of coastal-oceanic
      ecosystem interactions at a large scale and provides an estimate of annual
      consumption of reef prey by oceanic predators.

PMID- 22615798
TI  - Targeting FGFR4 inhibits hepatocellular carcinoma in preclinical mouse models.
AB  - The fibroblast growth factor (FGF)-FGF receptor (FGFR) signaling system plays
      critical roles in a variety of normal developmental and physiological processes.
      It is also well documented that dysregulation of FGF-FGFR signaling may have
      important roles in tumor development and progression. The FGFR4-FGF19 signaling
      axis has been implicated in the development of hepatocellular carcinomas (HCCs)
      in mice, and potentially in humans. In this study, we demonstrate that FGFR4 is
      required for hepatocarcinogenesis; the progeny of FGF19 transgenic mice, which
      have previously been shown to develop HCCs, bred with FGFR4 knockout mice fail to
      develop liver tumors. To further test the importance of FGFR4 in HCC, we
      developed a blocking anti-FGFR4 monoclonal antibody (LD1). LD1 inhibited: 1) FGF1
      and FGF19 binding to FGFR4, 2) FGFR4-mediated signaling, colony formation, and
      proliferation in vitro, and 3) tumor growth in a preclinical model of liver
      cancer in vivo. Finally, we show that FGFR4 expression is elevated in several
      types of cancer, including liver cancer, as compared to normal tissues. These
      findings suggest a modulatory role for FGFR4 in the development and progression
      of hepatocellular carcinoma and that FGFR4 may be an important and novel
      therapeutic target in treating this disease.

PMID- 22615797
TI  - The mbo operon is specific and essential for biosynthesis of mangotoxin in
      Pseudomonas syringae.
AB  - Mangotoxin is an antimetabolite toxin produced by certain Pseudomonas syringae
      pv. syringae strains. This toxin is an oligopeptide that inhibits ornithine N
      acetyl transferase, a key enzyme in the biosynthesis of ornithine and arginine.
      Previous studies have reported the involvement of the putative nonribosomal
      peptide synthetase MgoA in virulence and mangotoxin production. In this study, we
      analyse a new chromosomal region of P. syringae pv. syringae UMAF0158, which
      contains six coding sequences arranged as an operon (mbo operon). The mbo operon
      was detected in only mangotoxin-producing strains, and it was shown to be
      essential for the biosynthesis of this toxin. Mutants in each of the six ORFs of
      the mbo operon were partially or completely impaired in the production of the
      toxin. In addition, Pseudomonas spp. mangotoxin non-producer strains transformed
      with the mbo operon gained the ability to produce mangotoxin, indicating that
      this operon contains all the genetic information necessary for mangotoxin
      biosynthesis. The generation of a single transcript for the mbo operon was
      confirmed and supported by the allocation of a unique promoter and Rho
      independent terminator. The phylogenetic analysis of the P. syringae strains
      harbouring the mbo operon revealed that these strains clustered together.

PMID- 22615799
TI  - Feedback within the inter-cellular communication and tumorigenesis in carcinomas.
AB  - The classical somatic mutation theory (SMT) of carcinogenesis and metastasis
      postulates that malignant transformation occurs in cells that accumulate a
      sufficient amount of mutations in the appropriate oncogenes and/or tumor
      suppressor genes. These mutations result in cell-autonomous activation of the
      mutated cell and a growth advantage relative to neighboring cells. However, the
      SMT cannot completely explain many characteristics of carcinomas. Contrary to the
      cell-centered view of the SMT with respect to carcinogenesis, recent research has
      revealed evidence that the tumor microenvironment plays a role in carcinogenesis
      as well. In this review, we present a new model that accommodates the role of the
      tumor microenvironment in carcinogenesis and complements the classical SMT. Our
      "feedback" model emphasizes the role of an altered spatiotemporal communication
      between epithelial and stromal cells during carcinogenesis: a dysfunctional
      intracellular signaling in tumorigenic epithelial cells leads to inappropriate
      cellular responses to stimuli from associated stromal or inflammatory cells.
      Thus, a positive feedback loop of the information flow between parenchymal and
      stromal cells results. This constant communication between the stromal cells and
      the tumor cells causes a perpetually activated state of tumor cells analogous to
      resonance disaster.

PMID- 22615800
TI  - BC4707 is a major facilitator superfamily multidrug resistance transport protein
      from Bacillus cereus implicated in fluoroquinolone tolerance.
AB  - Transcriptional profiling highlighted a subset of genes encoding putative
      multidrug transporters in the pathogen Bacillus cereus that were up-regulated
      during stress produced by bile salts. One of these multidrug transporters
      (BC4707) was selected for investigation. Functional characterization of the
      BC4707 protein in Escherichia coli revealed a role in the energized efflux of
      xenobiotics. Phenotypic analyses after inactivation of the gene bc4707 in
      Bacillus cereus ATCC14579 suggested a more specific, but modest role in the
      efflux of norfloxacin. In addition to this, transcriptional analyses showed that
      BC4707 is also expressed during growth of B. cereus under non-stressful
      conditions where it may have a role in the normal physiology of the bacteria.
      Altogether, the results indicate that bc4707, which is part of the core genome of
      the B. cereus group of bacteria, encodes a multidrug resistance efflux protein
      that is likely involved in maintaining intracellular homeostasis during growth of
      the bacteria.

PMID- 22615801
TI  - Foraging behavior and success of a mesopelagic predator in the northeast Pacific
      Ocean: insights from a data-rich species, the northern elephant seal.
AB  - The mesopelagic zone of the northeast Pacific Ocean is an important foraging
      habitat for many predators, yet few studies have addressed the factors driving
      basin-scale predator distributions or inter-annual variability in foraging and
      breeding success. Understanding these processes is critical to reveal how
      conditions at sea cascade to population-level effects. To begin addressing these
      challenging questions, we collected diving, tracking, foraging success, and
      natality data for 297 adult female northern elephant seal migrations from 2004 to
      2010. During the longer post-molting migration, individual energy gain rates were
      significant predictors of pregnancy. At sea, seals focused their foraging effort
      along a narrow band corresponding to the boundary between the sub-arctic and sub
      tropical gyres. In contrast to shallow-diving predators, elephant seals target
      the gyre-gyre boundary throughout the year rather than follow the southward
      winter migration of surface features, such as the Transition Zone Chlorophyll
      Front. We also assessed the impact of added transit costs by studying seals at a
      colony near the southern extent of the species' range, 1,150 km to the south. A
      much larger proportion of seals foraged locally, implying plasticity in foraging
      strategies and possibly prey type. While these findings are derived from a single
      species, the results may provide insight to the foraging patterns of many other
      meso-pelagic predators in the northeast Pacific Ocean.

PMID- 22615802
TI  - Pattern classification of large-scale functional brain networks: identification
      of informative neuroimaging markers for epilepsy.
AB  - The accurate prediction of general neuropsychiatric disorders, on an individual
      basis, using resting-state functional magnetic resonance imaging (fMRI) is a
      challenging task of great clinical significance. Despite the progress to chart
      the differences between the healthy controls and patients at the group level, the
      pattern classification of functional brain networks across individuals is still
      less developed. In this paper we identify two novel neuroimaging measures that
      prove to be strongly predictive neuroimaging markers in pattern classification
      between healthy controls and general epileptic patients. These measures
      characterize two important aspects of the functional brain network in a
      quantitative manner: (i) coordinated operation among spatially distributed brain
      regions, and (ii) the asymmetry of bilaterally homologous brain regions, in terms
      of their global patterns of functional connectivity. This second measure offers a
      unique understanding of brain asymmetry at the network level, and, to the best of
      our knowledge, has not been previously used in pattern classification of
      functional brain networks. Using modern pattern-recognition approaches like
      sparse regression and support vector machine, we have achieved a cross-validated
      classification accuracy of 83.9% (specificity: 82.5%; sensitivity: 85%) across
      individuals from a large dataset consisting of 180 healthy controls and epileptic
      patients. We identified significantly changed functional pathways and subnetworks
      in epileptic patients that underlie the pathophysiological mechanism of the
      impaired cognitive functions. Specifically, we find that the asymmetry of brain
      operation for epileptic patients is markedly enhanced in temporal lobe and limbic
      system, in comparison with healthy individuals. The present study indicates that
      with specifically designed informative neuroimaging markers, resting-state fMRI
      can serve as a most promising tool for clinical diagnosis, and also shed light
      onto the physiology behind complex neuropsychiatric disorders. The systematic
      approaches we present here are expected to have wider applications in general
      neuropsychiatric disorders.

PMID- 22615804
TI  - Widespread climate change in the Himalayas and associated changes in local
      ecosystems.
AB  - BACKGROUND: Climate change in the Himalayas, a biodiversity hotspot, home of many
      sacred landscapes, and the source of eight largest rivers of Asia, is likely to
      impact the well-being of ~20% of humanity. However, despite the extraordinary
      environmental, cultural, and socio-economic importance of the Himalayas, and
      despite their rapidly increasing ecological degradation, not much is known about
      actual changes in the two most critical climatic variables: temperature and
      rainfall. Nor do we know how changes in these parameters might impact the
      ecosystems including vegetation phenology. METHODOLOGY/PRINCIPAL FINDINGS: By
      analyzing temperature and rainfall data, and NDVI (Normalized Difference
      Vegetation Index) values from remotely sensed imagery, we report significant
      changes in temperature, rainfall, and vegetation phenology across the Himalayas
      between 1982 and 2006. The average annual mean temperature during the 25 year
      period has increased by 1.5  degrees C with an average increase of 0.06  degrees
      C yr(-1). The average annual precipitation has increased by 163 mm or 6.52 mmyr(
      1). Since changes in temperature and precipitation are immediately manifested as
      changes in phenology of local ecosystems, we examined phenological changes in all
      major ecoregions. The average start of the growing season (SOS) seems to have
      advanced by 4.7 days or 0.19 days yr(-1) and the length of growing season (LOS)
      appears to have advanced by 4.7 days or 0.19 days yr(-1), but there has been no
      change in the end of the growing season (EOS). There is considerable spatial and
      seasonal variation in changes in climate and phenological parameters.
      CONCLUSIONS/SIGNIFICANCE: This is the first time that large scale climatic and
      phenological changes at the landscape level have been documented for the
      Himalayas. The rate of warming in the Himalayas is greater than the global
      average, confirming that the Himalayas are among the regions most vulnerable to
      climate change.

PMID- 22615803
TI  - Mathematical model of plasmid-mediated resistance to ceftiofur in commensal
      enteric Escherichia coli of cattle.
AB  - Antimicrobial use in food animals may contribute to antimicrobial resistance in
      bacteria of animals and humans. Commensal bacteria of animal intestine may serve
      as a reservoir of resistance-genes. To understand the dynamics of plasmid
      mediated resistance to cephalosporin ceftiofur in enteric commensals of cattle,
      we developed a deterministic mathematical model of the dynamics of ceftiofur
      sensitive and resistant commensal enteric Escherichia coli (E. coli) in the
      absence of and during parenteral therapy with ceftiofur. The most common
      treatment scenarios including those using a sustained-release drug formulation
      were simulated; the model outputs were in agreement with the available
      experimental data. The model indicated that a low but stable fraction of
      resistant enteric E. coli could persist in the absence of immediate ceftiofur
      pressure, being sustained by horizontal and vertical transfers of plasmids
      carrying resistance-genes, and ingestion of resistant E. coli. During parenteral
      therapy with ceftiofur, resistant enteric E. coli expanded in absolute number and
      relative frequency. This expansion was most influenced by parameters of
      antimicrobial action of ceftiofur against E. coli. After treatment (>5 weeks from
      start of therapy) the fraction of ceftiofur-resistant cells among enteric E.
      coli, similar to that in the absence of treatment, was most influenced by the
      parameters of ecology of enteric E. coli, such as the frequency of transfer of
      plasmids carrying resistance-genes, the rate of replacement of enteric E. coli by
      ingested E. coli, and the frequency of ceftiofur resistance in the latter.

PMID- 22615805
TI  - Geminivirus-mediated delivery of florigen promotes determinate growth in aerial
      organs and uncouples flowering from photoperiod in cotton.
AB  - BACKGROUND: Plant architecture and the timing and distribution of reproductive
      structures are fundamental agronomic traits shaped by patterns of determinate and
      indeterminate growth. Florigen, encoded by FLOWERING LOCUS T (FT) in Arabidopsis
      and SINGLE FLOWER TRUSS (SFT) in tomato, acts as a general growth hormone,
      advancing determinate growth. Domestication of upland cotton (Gossypium hirsutum)
      converted it from a lanky photoperiodic perennial to a highly inbred, compact day
      neutral plant that is managed as an annual row-crop. This dramatic change in
      plant architecture provides a unique opportunity to analyze the transition from
      perennial to annual growth. METHODOLOGY/PRINCIPAL FINDINGS: To explore these
      architectural changes, we addressed the role of day-length upon flowering in an
      ancestral, perennial accession and in a domesticated variety of cotton. Using a
      disarmed Cotton leaf crumple virus (CLCrV) as a transient expression system, we
      delivered FT to both cotton accessions. Ectopic expression of FT in ancestral
      cotton mimicked the effects of day-length, promoting photoperiod-independent
      flowering, precocious determinate architecture, and lanceolate leaf shape.
      Domesticated cotton infected with FT demonstrated more synchronized fruiting and
      enhanced "annualization". Transient expression of FT also facilitated simple
      crosses between wild photoperiodic and domesticated day-neutral accessions,
      effectively demonstrating a mechanism to increase genetic diversity among
      cultivated lines of cotton. Virus was not detected in the F(1) progeny,
      indicating that crosses made by this approach do not harbor recombinant DNA
      molecules. CONCLUSIONS: These findings extend our understanding of FT as a
      general growth hormone that regulates shoot architecture by advancing organ
      specific and age-related determinate growth. Judicious manipulation of FT could
      benefit cotton architecture to improve crop management.

PMID- 22615806
TI  - Transmission electron microscopy reveals distinct macrophage- and tick cell
      specific morphological stages of Ehrlichia chaffeensis.
AB  - BACKGROUND: Ehrlichia chaffeensis is an emerging tick-borne rickettsial pathogen
      responsible for human monocytic ehrlichiosis. Despite the induction of an active
      host immune response, the pathogen has evolved to persist in its vertebrate and
      tick hosts. Understanding how the organism progresses in tick and vertebrate host
      cells is critical in identifying effective strategies to block the pathogen
      transmission. Our recent molecular and proteomic studies revealed differences in
      numerous expressed proteins of the organism during its growth in different host
      environments. METHODOLOGY/PRINCIPAL FINDINGS: Transmission electron microscopy
      analysis was performed to assess morphological changes in the bacterium within
      macrophages and tick cells. The stages of pathogen progression observed included
      the attachment of the organism to the host cells, its engulfment and replication
      within a morulae by binary fission and release of the organisms from infected
      host cells by complete host cell lysis or by exocytosis. E. chaffeensis grown in
      tick cells was highly pleomorphic and appears to replicate by both binary fission
      and filamentous type cell divisions. The presence of Ehrlichia-like inclusions
      was also observed within the nucleus of both macrophages and tick cells. This
      observation was confirmed by confocal microscopy and immunoblot analysis.
      CONCLUSIONS/SIGNIFICANCE: Morphological differences in the pathogen's
      progression, replication, and processing within macrophages and tick cells
      provide further evidence that E. chaffeensis employs unique host-cell specific
      strategies in support of adaptation to vertebrate and tick cell environments.

PMID- 22615808
TI  - Presenting survey items one at a time compared to all at once decreases missing
      data without sacrificing validity in research with internet volunteers.
AB  - In two large web-based studies, across five distinct criteria, presenting survey
      items one-at-a-time was psychometrically either the same or better than
      presenting survey items all-at-once on a single web page to volunteer
      participants. In the one-at-a-time format, participants were no more likely to
      drop-out of the study (Criterion 1), and were much more likely to provide answers
      for the survey items (Criterion 2). Rehabilitating participants who otherwise
      would not have provided survey responses with the one-at-a-time format did not
      damage internal consistency of the measures (Criterion 3) nor did it negatively
      affect criterion validity (Criterion 4). Finally, the one-at-a-time format was
      more efficient with participants completing it more quickly than the all-at-once
      format (Criterion 5). In short, the one-at-a-time format results in less missing
      data with a shorter presentation time, and ultimately more power to detect
      relations among variables.

PMID- 22615807
TI  - Crystal structures of Lsm3, Lsm4 and Lsm5/6/7 from Schizosaccharomyces pombe.
AB  - Sm-like (Lsm) proteins are ubiquitous and function in many aspects of RNA
      metabolism, including pre-mRNA splicing, nuclear RNA processing, mRNA decay and
      miRNA biogenesis. Here three crystal structures including Lsm3, Lsm4 and Lsm5/6/7
      sub-complex from S. pombe are reported. These structures show that all the five
      individual Lsm subunits share a conserved Sm fold, and Lsm3, Lsm4, and Lsm5/6/7
      form a heptamer, a trimer and a hexamer within the crystal lattice, respectively.
      Analytical ultracentrifugation indicates that Lsm3 and Lsm5/6/7 sub-complex exist
      in solution as a heptamer and a hexamer, respectively while Lsm4 undergoes a
      dynamic equilibrium between monomer and trimer in solution. RNA binding assays
      show that Lsm2/3 and Lsm5/6/7 bind to oligo(U) whereas no RNA binding is observed
      for Lsm3 and Lsm4. Analysis of the inter-subunit interactions in Lsm5/6/7 reveals
      the organization order among Lsm5, Lsm6 and Lsm7.

PMID- 22615809
TI  - Coupling of glucose deprivation with impaired histone H2B monoubiquitination in
      tumors.
AB  - Metabolic reprogramming is associated with tumorigenesis. However, glucose
      metabolism in tumors is poorly understood. Here, we report that glucose levels
      are significantly lower in bulk tumor specimens than those in normal tissues of
      the same tissue origins. We show that mono-ubiquitinated histone H2B (uH2B) is a
      semi-quantitative histone marker for glucose. We further show that loss of uH2B
      occurs specifically in cancer cells from a wide array of tumor specimens of
      breast, colon, lung and additional 23 anatomic sites. In contrast, uH2B levels
      remain high in stromal tissues or non-cancerous cells in the tumor specimens.
      Taken together, our data suggest that glucose deficiency and loss of uH2B are
      novel properties of cancer cells in vivo, which may represent important
      regulatory mechanisms of tumorigenesis.

PMID- 22615810
TI  - Early warning indicators for HIV drug resistance in Cameroon during the year
      2010.
AB  - BACKGROUND: Rapid scale-up of antiretroviral therapy (ART) in resource-limited
      settings is accompanied with an increasing risk of HIV drug resistance (HIVDR),
      which in turn could compromise the performance of national ART rollout programme.
      In order to sustain the effectiveness of ART in a resource-limited country like
      Cameroon, HIVDR early warning indicators (EWI) may provide relevant corrective
      measures to support the control and therapeutic management of AIDS. METHODS: A
      retrospective study was conducted in 2010 among 40 ART sites (12 Approved
      Treatment Centers and 28 Management Units) distributed over the 10 regions of
      Cameroon. Five standardized EWIs were selected for the evaluation using data from
      January through December, among which: (1) Good ARV prescribing practices: target
      = 100%; (2) Patient lost to follow-up: target <= 20%; (3) Patient retention on
      first line ART: target >= 70%; (4) On-time drug pick-up: target >= 90%; (5) ARV
      drug supply continuity: target = 100%. Analysis was performed using a Data
      Quality Assessment tool, following WHO protocol. RESULTS: THE NUMBER OF SITES
      ATTAINING THE REQUIRED PERFORMANCE ARE: 90% (36/40) for EWI(1), 20% (8/40) for
      EWI(2); 20% (8/40) for EWI(3); 0% (0/37) for EWI(4); and 45% (17/38) for EWI 5.
      ARV prescribing practices were in conformity with the national guidelines in
      almost all the sites, whereas patient adherence to ART (EWI(2), EWI(3), and
      EWI(4)) was very low. A high rate of patients was lost-to-follow-up and others
      failing first line ART before 12 months of initiation. Discontinuity in drug
      supply observed in about half of the sites may negatively impact ARV prescription
      and patient adherence. These poor ART performances may also be due to low number
      of trained staff and community disengagement. CONCLUSIONS: The poor performance
      of the national ART programme, due to patient non-adherence and drug stock outs,
      requires corrective measures to limit risks of HIVDR emergence in Cameroon.

PMID- 22615811
TI  - The prognostic role of RASSF1A promoter methylation in breast cancer: a meta
      analysis of published data.
AB  - PURPOSE: Epigenetic alterations have been investigated as prognostic indicators
      in breast cancer but their translation into clinical practice has been impeded by
      a lack of appropriate validation. We present the results of a meta-analysis of
      the associations between RASSF1A promoter methylation status and both disease
      free survival (DFS) and overall survival (OS) in female breast cancer. METHODS:
      Eligible studies were identified through searching the PubMed, Web of Science and
      Embase databases. Studies were pooled and summary hazard ratios (HR) with
      corresponding confidence intervals (CIs) were calculated. Funnel plots were also
      carried out to evaluate publication bias. RESULTS: A total of 1795 patients from
      eight studies were included in the meta-analysis. There are eight studies which
      investigated DFS in 1795 cases. The relative hazard estimates ranged from 1.77
      5.64 with a combined HR of 2.75 (95%CI 1.96-3.84). The HR of RASSF1A promoter
      methylation on DFS adjusted for other potential prognostic factors was 2.54
      (95%CI 1.77-3.66). There has been five trials which analyzed the associations of
      RASSF1A promoter methylation status with OS in 1439 patients. The hazard
      estimates ranged from 1.21-6.90 with a combined random-effects estimates of 3.47
      (95%CI 1.44-8.34). OS reported in multivariate analysis was evaluated in four
      series comprising 1346 cases and the summarized random-effects HR estimate was
      3.35 (95%CI 1.14-9.85). Additionally, no publication bias was detected for both
      OS and DFS. CONCLUSION: The results of this meta-analysis suggest that RASSF1A
      promoter hypermethylation confers a higher risk of relapse and a worse survival
      in patients with breast cancer. Large prospective studies are now needed to
      establish the clinical utility of RASSF1A promoter methylation.

PMID- 22615813
TI  - New Dromaeosaurids (Dinosauria: Theropoda) from the lower cretaceous of Utah, and
      the evolution of the Dromaeosaurid tail.
AB  - BACKGROUND: The Yellow Cat Member of the Cedar Mountain Formation (Early
      Cretaceous, Barremian?--Aptian) of Utah has yielded a rich theropod fauna,
      including the coelurosaur Nedcolbertia justinhofmanni, the therizinosauroid
      Falcarius utahensis, the troodontid Geminiraptor suarezarum, and the
      dromaeosaurid Utahraptor ostrommaysorum. Recent excavation has uncovered three
      new dromaeosaurid specimens. One specimen, which we designate the holotype of the
      new genus and species Yurgovuchia doellingi, is represented by a partial axial
      skeleton and a partial left pubis. A second specimen consists of a right pubis
      and a possibly associated radius. The third specimen consists of a tail skeleton
      that is unique among known Cedar Mountain dromaeosaurids. METHODOLOGY/PRINCIPAL
      FINDINGS: Y. doellingi resembles Utahraptor ostrommaysorum in that its caudal
      prezygapophyses are elongated but not to the degree present in most
      dromaeosaurids. The specimen represented by the right pubis exhibits a pronounced
      pubic tubercle, a velociraptorine trait that is absent in Y. doellingi. The
      specimen represented by the tail skeleton exhibits the extreme elongation of the
      caudal prezygapophyses that is typical of most dromaeosaurids. Here we perform a
      phylogenetic analysis to determine the phylogenetic position of Y. doellingi.
      Using the resulting phylogeny as a framework, we trace changes in character
      states of the tail across Coelurosauria to elucidate the evolution of the
      dromaeosaurid tail. CONCLUSIONS/SIGNIFICANCE: The new specimens add to the known
      diversity of Dromaeosauridae and to the known diversity within the Yellow Cat
      paleofauna. Phylogenetic analysis places Y. doellingi in a clade with Utahraptor,
      Achillobator, and Dromaeosaurus. Character state distribution indicates that the
      presence of intermediate-length caudal prezygapophyses in that clade is not an
      evolutionarily precursor to extreme prezygapophyseal elongation but represents a
      secondary shortening of caudal prezygapophyses. It appears to represent part of a
      trend within Dromaeosauridae that couples an increase in tail flexibility with
      increasing size.

PMID- 22615812
TI  - Scavenger receptor CD36 expression contributes to adipose tissue inflammation and
      cell death in diet-induced obesity.
AB  - OBJECTIVE: The enlarged adipose tissue in obesity is characterized by
      inflammation, including the recruitment and infiltration of macrophages and
      lymphocytes. The objective of this study was to investigate the role of the
      scavenger receptor CD36 in high fat diet-induced obesity and adipose tissue
      inflammation and cell death. EXPERIMENTAL APPROACH: Obesity and adipose tissue
      inflammation was compared in CD36 deficient (CD36 KO) mice and wild type (WT)
      mice fed a high fat diet (60% kcal fat) for 16 weeks and the inflammatory
      response was studied in primary adipocytes and macrophages isolated from CD36 KO
      and WT mice. RESULTS: Compared to WT mice, CD36 KO mice fed a high fat diet
      exhibited reduced adiposity and adipose tissue inflammation, with decreased
      adipocyte cell death, pro-inflammatory cytokine expression and macrophage and T
      cell accumulation. In primary cell culture, the absence of CD36 expression in
      macrophages decreased pro-inflammatory cytokine, pro-apoptotic and ER stress gene
      expression in response to lipopolysaccharide (LPS). Likewise, CD36 deficiency in
      primary adipocytes reduced pro-inflammatory cytokine and chemokine secretion in
      response to LPS. Primary macrophage and adipocyte co-culture experiments showed
      that these cell types act synergistically in their inflammatory response to LPS
      and that CD36 modulates such synergistic effects. CONCLUSIONS: CD36 enhances
      adipose tissue inflammation and cell death in diet-induced obesity through its
      expression in both macrophages and adipocytes.

PMID- 22615814
TI  - Fostering critical thinking, reasoning, and argumentation skills through
      bioethics education.
AB  - Developing a position on a socio-scientific issue and defending it using a well
      reasoned justification involves complex cognitive skills that are challenging to
      both teach and assess. Our work centers on instructional strategies for fostering
      critical thinking skills in high school students using bioethical case studies,
      decision-making frameworks, and structured analysis tools to scaffold student
      argumentation. In this study, we examined the effects of our teacher professional
      development and curricular materials on the ability of high school students to
      analyze a bioethical case study and develop a strong position. We focused on
      student ability to identify an ethical question, consider stakeholders and their
      values, incorporate relevant scientific facts and content, address ethical
      principles, and consider the strengths and weaknesses of alternate solutions. 431
      students and 12 teachers participated in a research study using teacher cohorts
      for comparison purposes. The first cohort received professional development and
      used the curriculum with their students; the second did not receive professional
      development until after their participation in the study and did not use the
      curriculum. In order to assess the acquisition of higher-order justification
      skills, students were asked to analyze a case study and develop a well-reasoned
      written position. We evaluated statements using a scoring rubric and found highly
      significant differences (p<0.001) between students exposed to the curriculum
      strategies and those who were not. Students also showed highly significant gains
      (p<0.001) in self-reported interest in science content, ability to analyze socio
      scientific issues, awareness of ethical issues, ability to listen to and discuss
      viewpoints different from their own, and understanding of the relationship
      between science and society. Our results demonstrate that incorporating ethical
      dilemmas into the classroom is one strategy for increasing student motivation and
      engagement with science content, while promoting reasoning and justification
      skills that help prepare an informed citizenry.

PMID- 22615815
TI  - Regulation of the fruit-specific PEP carboxylase SlPPC2 promoter at early stages
      of tomato fruit development.
AB  - The SlPPC2 phosphoenolpyruvate carboxylase (PEPC; EC 4.1.1.31) gene from tomato
      (Solanum lycopersicum) is differentially and specifically expressed in expanding
      tissues of developing tomato fruit. We recently showed that a 1966 bp DNA
      fragment located upstream of the ATG codon of the SlPPC2 gene (GenBank AJ313434)
      confers appropriate fruit-specificity in transgenic tomato. In this study, we
      further investigated the regulation of the SlPPC2 promoter gene by analysing the
      SlPPC2 cis-regulating region fused to either the firefly luciferase (LUC) or the
      beta-glucuronidase (GUS) reporter gene, using stable genetic transformation and
      biolistic transient expression assays in the fruit. Biolistic analyses of 5'
      SlPPC2 promoter deletions fused to LUC in fruits at the 8(th) day after anthesis
      revealed that positive regulatory regions are mostly located in the distal region
      of the promoter. In addition, a 5' UTR leader intron present in the 1966 bp
      fragment contributes to the proper temporal regulation of LUC activity during
      fruit development. Interestingly, the SlPPC2 promoter responds to hormones
      (ethylene) and metabolites (sugars) regulating fruit growth and metabolism. When
      tested by transient expression assays, the chimeric promoter:LUC fusion
      constructs allowed gene expression in both fruit and leaf, suggesting that
      integration into the chromatin is required for fruit-specificity. These results
      clearly demonstrate that SlPPC2 gene is under tight transcriptional regulation in
      the developing fruit and that its promoter can be employed to drive transgene
      expression specifically during the cell expansion stage of tomato fruit. Taken
      together, the SlPPC2 promoter offers great potential as a candidate for driving
      transgene expression specifically in developing tomato fruit from various tomato
      cultivars.

PMID- 22615816
TI  - Genome-wide association studies identified three independent polymorphisms
      associated with alpha-tocopherol content in maize kernels.
AB  - Tocopherols are a class of four natural compounds that can provide nutrition and
      function as antioxidant in both plants and animals. Maize kernels have low alpha
      tocopherol content, the compound with the highest vitamin E activity, thus,
      raising the risk of vitamin E deficiency in human populations relying on maize as
      their primary vitamin E source. In this study, two insertion/deletions (InDels)
      within a gene encoding gamma-tocopherol methyltransferase, Zea mays VTE4
      (ZmVTE4), and a single nucleotide polymorphism (SNP) located ~85 kb upstream of
      ZmVTE4 were identified to be significantly associated with alpha-tocopherol
      levels in maize kernels by conducting an association study with a panel of ~500
      diverse inbred lines. Linkage analysis in three populations that segregated at
      either one of these three polymorphisms but not at the other two suggested that
      the three polymorphisms could affect alpha-tocopherol content independently.
      Furthermore, we found that haplotypes of the two InDels could explain ~33% of
      alpha-tocopherol variation in the association panel, suggesting ZmVTE4 is a major
      gene involved in natural phenotypic variation of alpha-tocopherol. One of the two
      InDels is located within the promoter region and associates with ZmVTE4
      transcript level. This information can not only help in understanding the
      underlying mechanism of natural tocopherol variations in maize kernels, but also
      provide valuable markers for marker-assisted breeding of alpha-tocopherol content
      in maize kernels, which will then facilitate the improvement of maize as a better
      source of daily vitamin E nutrition.

PMID- 22615817
TI  - A novel mutation in LEPRE1 that eliminates only the KDEL ER- retrieval sequence
      causes non-lethal osteogenesis imperfecta.
AB  - Prolyl 3-hydroxylase 1 (P3H1), encoded by the LEPRE1 gene, forms a molecular
      complex with cartilage-associated protein (CRTAP) and cyclophilin B (encoded by
      PPIB) in the endoplasmic reticulum (ER). This complex is responsible for one step
      in collagen post-translational modification, the prolyl 3-hydroxylation of
      specific proline residues, specifically alpha1(I) Pro986. P3H1 provides the
      enzymatic activity of the complex and has a Lys-Asp-Glu-Leu (KDEL) ER-retrieval
      sequence at the carboxyl terminus. Loss of function mutations in LEPRE1 lead to
      the Pro986 residue remaining unmodified and lead to slow folding and excessive
      helical post-translational modification of type I collagen, which is seen in both
      dominant and recessive osteogenesis imperfecta (OI). Here, we present the case of
      siblings with non-lethal OI due to novel compound heterozygous mutations in
      LEPRE1 (c.484delG and c.2155dupC). The results of RNA analysis and real-time PCR
      suggest that mRNA with c.2155dupC escapes from nonsense-mediated RNA decay.
      Without the KDEL ER- retrieval sequence, the product of the c.2155dupC variant
      cannot be retained in the ER. This is the first report of a mutation in LEPRE1
      that eliminates only the KDEL ER-retrieval sequence, whereas other functional
      domains remain intact. Our study shows, for the first time, that the KDEL ER-
      retrieval sequence is essential for P3H1 functionality and that a defect in KDEL
      is sufficient for disease onset.

PMID- 22615819
TI  - The antiquity of the Rhine River: stratigraphic coverage of the dinotheriensande
      (eppelsheim formation) of the Mainz Basin (Germany).
AB  - BACKGROUND: Mammalian fossils from the Eppelsheim Formation (Dinotheriensande)
      have been a benchmark for Neogene vertebrate palaeontology since 200 years.
      Worldwide famous sites like Eppelsheim serve as key localities for
      biochronologic, palaeobiologic, environmental, and mammal community studies. So
      far the formation is considered to be of early Late Miocene age (~9.5 Ma,
      Vallesian), representing the oldest sediments of the Rhine River. The
      stratigraphic unity of the formation and of its fossil content was disputed at
      times, but persists unresolved. PRINCIPAL FINDINGS: Here we investigate a new
      fossil sample from Sprendlingen, composed by over 300 mammalian specimens and
      silicified wood. The mammals comprise entirely Middle Miocene species, like
      cervids Dicrocerus elegans, Paradicrocerus elegantulus, and deinotheres
      Deinotherium bavaricum and D. levius. A stratigraphic evaluation of Miocene
      Central European deer and deinothere species proof the stratigraphic inhomogenity
      of the sample, and suggest late Middle Miocene (~12.5 Ma) reworking of early
      Middle Miocene (~15 Ma) sediments. This results agree with taxonomic and
      palaeoclimatic analysis of plant fossils from above and within the mammalian
      assemblage. Based on the new fossil sample and published data three
      biochronologic levels within the Dinotheriensand fauna can be differentiated,
      corresponding to early Middle Miocene (late Orleanian to early Astaracian), late
      Middle Miocene (late Astaracian), and early Late Miocene (Vallesian) ages.
      CONCLUSIONS/SIGNIFICANCE: This study documents complex faunal mixing of classical
      Dinotheriensand fauna, covering at least six million years, during a time of low
      subsidence in the Mainz Basin and shifts back the origination of the Rhine River
      by some five million years. Our results have severe implications for
      biostratigraphy and palaeobiology of the Middle to Late Miocene. They suggest
      that turnover events may be obliterated and challenge the proposed
      'supersaturated' biodiversity, caused by Middle Miocene superstites, of Vallesian
      ecosystems in Central Europe.

PMID- 22615818
TI  - Increased levels of inflammatory cytokines and endothelin-1 in alveolar
      macrophages from patients with chronic heart failure.
AB  - BACKGROUND: Pathophysiological interactions between heart and lungs in heart
      failure (HF) are well recognized. We investigated whether expression of different
      factors known to be increased in the myocardium and/or the circulation in HF is
      also increased in alveolar macrophages in HF. METHODOLOGY/PRINCIPAL FINDINGS:
      Lung function, hemodynamic parameters, gene expression in alveolar macrophages,
      and plasma levels in the pulmonary and femoral arteries of HF patients (n = 20)
      were compared to control subjects (n = 16). Our principal findings were: (1) Lung
      function was significantly lower in HF patients compared to controls (P<0.05).
      (2) mRNA levels of ET-1, tumor necrosis factor (TNF)-alpha and interleukin-6 (IL
      6) were increased in alveolar macrophages from HF patients. (3) Plasma levels of
      ET-1, TNFalpha, IL-6 and MCP-1 were significantly increased in HF patients,
      whereas our data indicate a net pulmonary release of MCP-1 into the circulation
      in HF. CONCLUSIONS/SIGNIFICANCE: Several important cytokines and ET-1 are induced
      in alveolar macrophages in human HF. Further studies should clarify whether
      increased synthesis of these factors affects pulmonary remodeling and, directly
      or indirectly, adversely affects the failing myocardium.

PMID- 22615821
TI  - Elucidating the mechanisms of influenza virus recognition by Ncr1.
AB  - Natural killer (NK) cells are innate cytotoxic lymphocytes that specialize in the
      defense against viral infection and oncogenic transformation. Their action is
      tightly regulated by signals derived from inhibitory and activating receptors;
      the later include proteins such as the Natural Cytotoxicity Receptors (NCRs:
      NKp46, NKp44 and NKp30). Among the NCRs, NKp46 is the only receptor that has a
      mouse orthologue named Ncr1. NKp46/Ncr1 is also a unique marker expressed on NK
      and on Lymphoid tissue inducer (LTI) cells and it was implicated in the control
      of various viral infections, cancer and diabetes. We have previously shown that
      human NKp46 recognizes viral hemagglutinin (HA) in a sialic acid-dependent manner
      and that the O-glycosylation is essential for the NKp46 binding to viral HA. Here
      we studied the molecular interactions between Ncr1 and influenza viruses. We show
      that Ncr1 recognizes influenza virus in a sialic acid dependent manner and that N
      glycosylation is important for this binding. Surprisingly we demonstrate that
      none of the predicted N-glycosilated residues of Ncr1 are essential for its
      binding to influenza virus and we thus conclude that other, yet unidentified N
      glycosilated residues are responsible for its recognition. We have demonstrated
      that N glycosylation play little role in the recognition of mouse tumor cell
      lines and also showed the in-vivo importance of Ncr1 in the control of influenza
      virus infection by infecting C57BL/6 and BALB/c mice knockout for Ncr1 with
      influenza.

PMID- 22615820
TI  - Paraoxonase 1 polymorphism and prenatal pesticide exposure associated with
      adverse cardiovascular risk profiles at school age.
AB  - BACKGROUND: Prenatal environmental factors might influence the risk of developing
      cardiovascular disease later in life. The HDL-associated enzyme paraoxonase 1
      (PON1) has anti-oxidative functions that may protect against atherosclerosis. It
      also hydrolyzes many substrates, including organophosphate pesticides. A common
      polymorphism, PON1 Q192R, affects both properties, but a potential interaction
      between PON1 genotype and pesticide exposure on cardiovascular risk factors has
      not been investigated. We explored if the PON1 Q192R genotype affects
      cardiovascular risk factors in school-age children prenatally exposed to
      pesticides. METHODS: Pregnant greenhouse-workers were categorized as high,
      medium, or not exposed to pesticides. Their children underwent a standardized
      examination at age 6-to-11 years, where blood pressure, skin folds, and other
      anthropometric parameters were measured. PON1-genotype was determined for 141
      children (88 pesticide exposed and 53 unexposed). Serum was analyzed for insulin
      like growth factor I (IGF-I), insulin-like growth factor binding protein 3
      (IGFBP3), insulin and leptin. Body fat percentage was calculated from skin fold
      thicknesses. BMI results were converted to age and sex specific Z-scores.
      RESULTS: Prenatally pesticide exposed children carrying the PON1 192R-allele had
      higher abdominal circumference, body fat content, BMI Z-scores, blood pressure,
      and serum concentrations of leptin and IGF-I at school age than unexposed
      children. The effects were related to the prenatal exposure level. For children
      with the PON1 192QQ genotype, none of the variables was affected by prenatal
      pesticide exposure. CONCLUSION: Our results indicate a gene-environment
      interaction between prenatal pesticide exposure and the PON1 gene. Only exposed
      children with the R-allele developed adverse cardiovascular risk profiles thought
      to be associated with the R-allele.

PMID- 22615822
TI  - Analysis of spatial point patterns in nuclear biology.
AB  - There is considerable interest in cell biology in determining whether, and to
      what extent, the spatial arrangement of nuclear objects affects nuclear function.
      A common approach to address this issue involves analyzing a collection of images
      produced using some form of fluorescence microscopy. We assume that these images
      have been successfully pre-processed and a spatial point pattern representation
      of the objects of interest within the nuclear boundary is available. Typically in
      these scenarios, the number of objects per nucleus is low, which has consequences
      on the ability of standard analysis procedures to demonstrate the existence of
      spatial preference in the pattern. There are broadly two common approaches to
      look for structure in these spatial point patterns. First a spatial point pattern
      for each image is analyzed individually, or second a simple normalization is
      performed and the patterns are aggregated. In this paper we demonstrate using
      synthetic spatial point patterns drawn from predefined point processes how
      difficult it is to distinguish a pattern from complete spatial randomness using
      these techniques and hence how easy it is to miss interesting spatial preferences
      in the arrangement of nuclear objects. The impact of this problem is also
      illustrated on data related to the configuration of PML nuclear bodies in
      mammalian fibroblast cells.

PMID- 22615823
TI  - Risk assessment of gastric cancer caused by Helicobacter pylori using CagA
      sequence markers.
AB  - BACKGROUND: As a marker of Helicobacter pylori, Cytotoxin-associated gene A
      (cagA) has been revealed to be the major virulence factor causing gastroduodenal
      diseases. However, the molecular mechanisms that underlie the development of
      different gastroduodenal diseases caused by cagA-positive H. pylori infection
      remain unknown. Current studies are limited to the evaluation of the correlation
      between diseases and the number of Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs in the CagA
      strain. To further understand the relationship between CagA sequence and its
      virulence to gastric cancer, we proposed a systematic entropy-based approach to
      identify the cancer-related residues in the intervening regions of CagA and
      employed a supervised machine learning method for cancer and non-cancer cases
      classification. METHODOLOGY: An entropy-based calculation was used to detect key
      residues of CagA intervening sequences as the gastric cancer biomarker. For each
      residue, both combinatorial entropy and background entropy were calculated, and
      the entropy difference was used as the criterion for feature residue selection.
      The feature values were then fed into Support Vector Machines (SVM) with the
      Radial Basis Function (RBF) kernel, and two parameters were tuned to obtain the
      optimal F value by using grid search. Two other popular sequence classification
      methods, the BLAST and HMMER, were also applied to the same data for comparison.
      CONCLUSION: Our method achieved 76% and 71% classification accuracy for Western
      and East Asian subtypes, respectively, which performed significantly better than
      BLAST and HMMER. This research indicates that small variations of amino acids in
      those important residues might lead to the virulence variance of CagA strains
      resulting in different gastroduodenal diseases. This study provides not only a
      useful tool to predict the correlation between the novel CagA strain and
      diseases, but also a general new framework for detecting biological sequence
      biomarkers in population studies.

PMID- 22615824
TI  - Prevalence of allergic disorders among primary school-aged children in Madinah,
      Saudi Arabia: two-stage cross-sectional survey.
AB  - BACKGROUND: There are limited data on the epidemiology of allergic disorders in
      Saudi Arabia. Such data are needed for, amongst other things, helping to plan
      service provision at a time when there is considerable investment taking place in
      national healthcare development. We sought to estimate the prevalence of atopic
      eczema, allergic rhinitis and asthma in primary school children in Madinah, Saudi
      Arabia. METHODS AND FINDINGS: We conducted a two-stage cross-sectional survey of
      schoolchildren in Madinah. Children were recruited from 38 randomly selected
      schools. Questionnaires were sent to the parents of all 6,139 6-8 year old
      children in these schools. These parental-completed questionnaires incorporated
      questions from the International Study of Asthma and Allergies in Childhood
      (ISAAC), which had previously been validated for use in Arab populations. We
      undertook descriptive analyses, using the Generalized Estimating Equation (GEE)
      to calculate 95% confidence intervals. The overall response rate was 85.9% (n =
      5,188), 84.6% for girls and 86.2% for boys, respectively. Overall, parents
      reported symptoms suggestive of a history of eczema in 10.3% (95%CI 9.4, 11.4),
      rhinitis in 24.2% (95%CI 22.3, 26.2) and asthma in 23.6% (95%CI 21.3, 26.0) of
      children. Overall, 41.7% (95%CI 39.1, 44.4) of children had symptoms suggestive
      of at least one allergic disorder, with a substantial minority manifesting
      symptoms indicative of co-morbid allergic disease. Comparison of these symptom
      based prevalence estimates with reports of clinician-diagnosed disease suggested
      that the majority of children with eczema and asthma had been diagnosed, but only
      a minority (17.4%) of children had been diagnosed with rhinitis. International
      comparisons indicated that children in Madinah have amongst the highest
      prevalence of allergic problems in the world. CONCLUSIONS: Symptoms indicative of
      allergic disease are very common in primary school-aged children in Madinah,
      Saudi Arabia, with figures comparable to the highest risk regions in the world.

PMID- 22615825
TI  - Generalized DNA barcode design based on Hamming codes.
AB  - The diversity and scope of multiplex parallel sequencing applications is steadily
      increasing. Critically, multiplex parallel sequencing applications methods rely
      on the use of barcoded primers for sample identification, and the quality of the
      barcodes directly impacts the quality of the resulting sequence data. Inspection
      of the recent publications reveals a surprisingly variable quality of the
      barcodes employed. Some barcodes are made in a semi empirical fashion, without
      quantitative consideration of error correction or minimal distance properties.
      After systematic comparison of published barcode sets, including commercially
      distributed barcoded primers from Illumina and Epicentre, methods for improved,
      Hamming code-based sequences are suggested and illustrated. Hamming barcodes can
      be employed for DNA tag designs in many different ways while preserving minimal
      distance and error-correcting properties. In addition, Hamming barcodes remain
      flexible with regard to essential biological parameters such as sequence
      redundancy and GC content. Wider adoption of improved Hamming barcodes is
      encouraged in multiplex parallel sequencing applications.

PMID- 22615826
TI  - Characterization of digestive enzymes of bruchid parasitoids-initial steps for
      environmental risk assessment of genetically modified legumes.
AB  - Genetically modified (GM) legumes expressing the alpha-amylase inhibitor 1
      (alphaAI-1) from Phaseolus vulgaris L. or cysteine protease inhibitors are
      resistant to several bruchid pests (Coleoptera: Chrysomelidae). In addition, the
      combination of plant resistance factors together with hymenopteran parasitoids
      can substantially increase the bruchid control provided by the resistance alone.
      If the strategy of combining a bruchid-resistant GM legume and biological control
      is to be effective, the insecticidal trait must not adversely affect bruchid
      antagonists. The environmental risk assessment of such GM legumes includes the
      characterization of the targeted enzymes in the beneficial species and the
      assessment of the in vitro susceptibility to the resistance factor. The digestive
      physiology of bruchid parasitoids remain relatively unknown, and their
      susceptibility to alphaAI-1 has never been investigated. We have detected alpha
      amylase and serine protease activities in all five bruchid parasitoid species
      tested. Thus, the deployment of GM legumes expressing cysteine protease
      inhibitors to control bruchids should be compatible with the use of parasitoids.
      In vitro inhibition studies showed that sensitivity of alpha-amylase activity to
      alphaAI-1 in the parasitoids was comparable to that in the target species. Direct
      feeding assays revealed that harmful effects of alpha-amylase inhibitors on
      bruchid parasitoids cannot be discounted and need further evaluation.

PMID- 22615827
TI  - A proposed taxonomy of anaerobic fungi (class neocallimastigomycetes) suitable
      for large-scale sequence-based community structure analysis.
AB  - Anaerobic fungi are key players in the breakdown of fibrous plant material in the
      rumen, but not much is known about the composition and stability of fungal
      communities in ruminants. We analyzed anaerobic fungi in 53 rumen samples from
      farmed sheep (4 different flocks), cattle, and deer feeding on a variety of
      diets. Denaturing gradient gel electrophoresis fingerprinting of the internal
      transcribed spacer 1 (ITS1) region of the rrn operon revealed a high diversity of
      anaerobic fungal phylotypes across all samples. Clone libraries of the ITS1
      region were constructed from DNA from 11 rumen samples that had distinctly
      different fungal communities. A total of 417 new sequences were generated to
      expand the number and diversity of ITS1 sequences available. Major phylogenetic
      groups of anaerobic fungi in New Zealand ruminants belonged to the genera
      Piromyces, Neocallimastix, Caecomyces and Orpinomyces. In addition, sequences
      forming four novel clades were obtained, which may represent so far undetected
      genera or species of anaerobic fungi. We propose a revised phylogeny and
      pragmatic taxonomy for anaerobic fungi, which was tested and proved suitable for
      analysis of datasets stemming from high-throughput next-generation sequencing
      methods. Comparing our revised taxonomy to the taxonomic assignment of sequences
      deposited in the GenBank database, we believe that >29% of ITS1 sequences derived
      from anaerobic fungal isolates or clones are misnamed at the genus level.

PMID- 22615828
TI  - Combined use of serum adiponectin and tumor necrosis factor-alpha receptor 2
      levels was comparable to 2-hour post-load glucose in diabetes prediction.
AB  - BACKGROUND: Adipose tissue inflammation and dysregulated adipokine secretion are
      implicated in obesity-related insulin resistance and type 2 diabetes. We
      evaluated the use of serum adiponectin, an anti-inflammatory adipokine, and
      several proinflammatory adipokines, as biomarkers of diabetes risk and whether
      they add to traditional risk factors in diabetes prediction. METHODS: We studied
      1300 non-diabetic subjects from the prospective Hong Kong Cardiovascular Risk
      Factor Prevalence Study (CRISPS). Serum adiponectin, tumor necrosis factor-alpha
      receptor 2 (TNF-alpha R2), interleukin-6 (IL-6), adipocyte-fatty acid binding
      protein (A-FABP) and high-sensitivity C-reactive protein (hsCRP) were measured in
      baseline samples. RESULTS: Seventy-six participants developed diabetes over 5.3
      years (median). All five biomarkers significantly improved the log-likelihood of
      diabetes in a clinical diabetes prediction (CDP) model including age, sex, family
      history of diabetes, smoking, physical activity, hypertension, waist
      circumference, fasting glucose and dyslipidaemia. In ROC curve analysis,
      "adiponectin + TNF-alpha R2" improved the area under ROC curve (AUC) of the CDP
      model from 0.802 to 0.830 (P = 0.03), rendering its performance comparable to the
      "CDP + 2-hour post-OGTT glucose" model (AUC = 0.852, P = 0.30). A biomarker risk
      score, derived from the number of biomarkers predictive of diabetes (low
      adiponectin, high TNF-alpha R2), had similar performance when added to the CDP
      model (AUC = 0.829 [95% CI: 0.808-0.849]). CONCLUSIONS: The combined use of serum
      adiponectin and TNF-alpha R2 as biomarkers provided added value over traditional
      risk factors for diabetes prediction in Chinese and could be considered as an
      alternative to the OGTT.

PMID- 22615829
TI  - Comparing HLA shared epitopes in French Caucasian patients with scleroderma.
AB  - Although many studies have analyzed HLA allele frequencies in several ethnic
      groups in patients with scleroderma (SSc), none has been done in French Caucasian
      patients and none has evaluated which one of the common amino acid sequences,
      (67)FLEDR(71), shared by HLA-DRB susceptibility alleles, or (71)TRAELDT(77),
      shared by HLA-DQB1 susceptibility alleles in SSc, was the most important to
      develop the disease. HLA-DRB and DQB typing was performed for a total of 468
      healthy controls and 282 patients with SSc allowing FLEDR and TRAELDT analyses.
      Results were stratified according to patient's clinical subtypes and autoantibody
      status. Moreover, standardized HLA-DRbeta1 and DRbeta5 reverse transcriptase
      Taqman PCR assays were developed to quantify beta1 and beta5 mRNA in 20 subjects
      with HLA-DRB1*15 and/or DRB1*11 haplotypes. FLEDR motif is highly associated with
      diffuse SSc (chi(2) = 28.4, p<10-6) and with anti-topoisomerase antibody (ATA)
      production (chi(2) = 43.9, p<10-9) whereas TRAELDT association is weaker in both
      subgroups (chi(2) = 7.2, p = 0.027 and chi(2) = 14.6, p = 0.0007 respectively).
      Moreover, FLEDR motif- association among patients with diffuse SSc remains
      significant only in ATA subgroup. The risk to develop ATA positive SSc is higher
      with double dose FLEDR than single dose with respectively, adjusted standardised
      residuals of 5.1 and 2.6. The increase in FLEDR motif is mostly due to the higher
      frequency of HLA-DRB1*11 and DRB1*15 haplotypes. Furthermore, FLEDR is always
      carried by the most abundantly expressed beta chain: beta1 in HLA DRB1*11
      haplotypes and beta5 in HLA-DRB1*15 haplotypes.In French Caucasian patients with
      SSc, FLEDR is the main presenting motif influencing ATA production in dcSSc.
      These results open a new field of potential therapeutic applications to interact
      with the FLEDR peptide binding groove and prevent ATA production, a hallmark of
      severity in SSc.

PMID- 22615830
TI  - Enzymatic analysis of recombinant Japanese encephalitis virus NS2B(H)-NS3pro
      protease with fluorogenic model peptide substrates.
AB  - BACKGROUND: Japanese encephalitis virus (JEV), a member of the Flaviviridae
      family, causes around 68,000 encephalitis cases annually, of which 20-30% are
      fatal, while 30-50% of the recovered cases develop severe neurological sequelae.
      Specific antivirals for JEV would be of great importance, particularly in those
      cases where the infection has become persistent. Being indispensable for
      flaviviral replication, the NS2B-NS3 protease is a promising target for design of
      anti-flaviviral inhibitors. Contrary to related flaviviral proteases, the JEV
      NS2B-NS3 protease is structurally and mechanistically much less characterized.
      Here we aimed at establishing a straightforward procedure for cloning,
      expression, purification and biochemical characterization of JEV NS2B(H)-NS3pro
      protease. METHODOLOGY/PRINCIPAL FINDINGS: The full-length sequence of JEV NS2B
      NS3 genotype III strain JaOArS 982 was obtained as a synthetic gene. The sequence
      of NS2B(H)-NS3pro was generated by splicing by overlap extension PCR (SOE-PCR)
      and cloned into the pTrcHisA vector. Hexahistidine-tagged NS2B(H)-NS3pro,
      expressed in E. coli as soluble protein, was purified to >95% purity by a single
      step immobilized metal affinity chromatography. SDS-PAGE and immunoblotting of
      the purified enzyme demonstrated NS2B(H)-NS3pro precursor and its autocleavage
      products, NS3pro and NS2B(H), as 36, 21, and 10 kDa bands, respectively. Kinetic
      parameters, K(m) and k(cat), for fluorogenic protease model substrates, Boc-GRR
      amc, Boc-LRR-amc, Ac-nKRR-amc, Bz-nKRR-amc, Pyr-RTKR-amc and Abz-(R)(4)SAG-nY
      amide, were obtained using inner filter effect correction. The highest catalytic
      efficiency k(cat)/K(m) was found for Pyr-RTKR-amc (k(cat)/K(m): 1962.96 +/- 85.0
      M(-1) s(-1)) and the lowest for Boc-LRR-amc (k(cat)/K(m): 3.74+/-0.3 M(-1) s(
      1)). JEV NS3pro is inhibited by aprotinin but to a lesser extent than DEN and WNV
      NS3pro. CONCLUSIONS/SIGNIFICANCE: A simplified procedure for the cloning,
      overexpression and purification of the NS2B(H)-NS3pro was established which is
      generally applicable to other flaviviral proteases. Kinetic parameters obtained
      for a number of model substrates and inhibitors, are useful for the
      characterization of substrate specificity and eventually for the design of high
      throughput assays aimed at antiviral inhibitor discovery.

PMID- 22615831
TI  - Hyperphosphorylation and cleavage at D421 enhance tau secretion.
AB  - It is well established that tau pathology propagates in a predictable manner in
      Alzheimer's disease (AD). Moreover, tau accumulates in the cerebrospinal fluid
      (CSF) of AD's patients. The mechanisms underlying the propagation of tau
      pathology and its accumulation in the CSF remain to be elucidated. Recent studies
      have reported that human tau was secreted by neurons and non-neuronal cells when
      it was overexpressed indicating that tau secretion could contribute to the
      spreading of tau pathology in the brain and could lead to its accumulation in the
      CSF. In the present study, we showed that the overexpression of human tau
      resulted in its secretion by Hela cells. The main form of tau secreted by these
      cells was cleaved at the C-terminal. Surprisingly, secreted tau was
      dephosphorylated at several sites in comparison to intracellular tau which
      presented a strong immunoreactivity to all phospho-dependent antibodies tested.
      Our data also revealed that phosphorylation and cleavage of tau favored its
      secretion by Hela cells. Indeed, the mimicking of phosphorylation at 12 sites
      known to be phosphorylated in AD enhanced tau secretion. A mutant form of tau
      truncated at D421, the preferential cleavage site of caspase-3, was also
      significantly more secreted than wild-type tau. Taken together, our results
      indicate that hyperphosphorylation and cleavage of tau by favoring its secretion
      could contribute to the propagation of tau pathology in the brain and its
      accumulation in the CSF.

PMID- 22615832
TI  - Metabolic adaptation of Ralstonia solanacearum during plant infection: a
      methionine biosynthesis case study.
AB  - MetE and MetH are two distinct enzymes that catalyze a similar biochemical
      reaction during the last step of methionine biosynthesis, MetH being a cobalamin
      dependent enzyme whereas MetE activity is cobalamin-independent. In this work, we
      show that the last step of methionine synthesis in the plant pathogen Ralstonia
      solanacearum is under the transcriptional control of the master pathogenicity
      regulator HrpG. This control is exerted essentially on metE expression through
      the intermediate regulator MetR. Expression of metE is strongly and specifically
      induced in the presence of plant cells in a hrpG- and metR-dependent manner. metE
      and metR mutants are not auxotrophic for methionine and not affected for growth
      inside the plant but produce significantly reduced disease symptoms on tomato
      whereas disruption of metH has no impact on pathogenicity. The finding that the
      pathogen preferentially induces metE expression rather than metH in the presence
      of plant cells is indicative of a probable metabolic adaptation to physiological
      host conditions since this induction of metE occurs in an environment in which
      cobalamin, the required co-factor for MetH, is absent. It also shows that MetE
      and MetH are not functionally redundant and are deployed during specific stages
      of the bacteria lifecycle, the expression of metE and metH being controlled by
      multiple and distinct signals.

PMID- 22615833
TI  - Sex allocation in relation to host races in the brood-parasitic common cuckoo
      (Cuculus canorus).
AB  - Sex allocation theory and empirical evidence both suggest that natural selection
      should favour maternal control of offspring sex ratio in relation to their
      ability to invest in the offspring. Generalist parasites constitute a
      particularly interesting group to test this theory as different females commonly
      utilize different host species showing large variation in provisioning ability.
      The common cuckoo (Cuculus canorus) is a generalist brood parasite that lays its
      eggs in the nest of many different passerine birds, but each female tends to
      specialize on one particular host species giving rise to highly specialized host
      races. The different host species show large variation in their ability to invest
      in the parasitic offspring, presenting an opportunity for female cuckoos to bias
      offspring sex ratio in relation to host species quality. Here, we investigate
      host-race specific sex allocation controlling for maternal identity in the common
      cuckoo. We found no evidence of any significant relationship between host race
      and sex ratio in one sympatric population harbouring three different host races,
      or in a total of five geographically separated populations. There was also no
      significant association between host quality, as determined by species-specific
      female host body mass, and cuckoo sex ratio. Finally, we found no significant
      relationship between individual cuckoo maternal quality, as determined by her egg
      volume, and sex ratio within each host race. We conclude that the generalist
      brood-parasitic common cuckoo show no significant sex-ratio bias in relation to
      host race and discuss this finding in light of gene flow and host adaptations.

PMID- 22615834
TI  - Epigenetic repression of RARRES1 is mediated by methylation of a proximal
      promoter and a loss of CTCF binding.
AB  - BACKGROUND: The cis-acting promoter element responsible for epigenetic silencing
      of retinoic acid receptor responder 1 (RARRES1) by methylation is unclear.
      Likewise, how aberrant methylation interplays effectors and thus affects breast
      neoplastic features remains largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: We
      first compared methylation occurring at the sequences (-664~+420) flanking the
      RARRES1 promoter in primary breast carcinomas to that in adjacent benign tissues.
      Surprisingly, tumor cores displayed significantly elevated methylation occurring
      solely at the upstream region (-664~-86), while the downstream element (-85~+420)
      proximal to the transcriptional start site (+1) remained largely unchanged. Yet,
      hypermethylation at the former did not result in appreciable silencing effect. In
      contrast, the proximal sequence displayed full promoter activity and methylation
      of which remarkably silenced RARRES1 transcription. This phenomenon was
      recapitulated in breast cancer cell lines, in which methylation at the proximal
      region strikingly coincided with downregulation. We also discovered that CTCF
      occupancy was enriched at the unmethylayed promoter bound with transcription
      active histone markings. Furthermore, knocking-down CTCF expression hampered
      RARRES1 expression, suggesting CTCF positively regulated RARRES1 transcription
      presumably by binding to unmethylated promoter poised at transcription-ready
      state. Moreover, RARRES1 restoration not only impeded cell invasion but also
      promoted death induced by chemotherapeutic agents, denoting its tumor suppressive
      effect. Its role of attenuating invasion agreed with data generated from clinical
      specimens revealing that RARRES1 was generally downregulated in metastatic lymph
      nodes compared to the tumor cores. CONCLUSION/SIGNIFICANCE: This report
      delineated silencing of RARRES1 by hypermethylation is occurring at a proximal
      promoter element and is associated with a loss of binding to CTCF, an activator
      for RARRES1 expression. We also revealed the tumor suppressive roles exerted by
      RARRES1 in part by promoting breast epithelial cell death and by impeding cell
      invasion that is an important property for metastatic spread.

PMID- 22615835
TI  - Morphological and pathological evolution of the brain microcirculation in aging
      and Alzheimer's disease.
AB  - Key pathological hallmarks of Alzheimer's disease (AD), including amyloid
      plaques, cerebral amyloid angiopathy (CAA) and neurofibrillary tangles do not
      completely account for cognitive impairment, therefore other factors such as
      cardiovascular and cerebrovascular pathologies, may contribute to AD. In order to
      elucidate the microvascular changes that contribute to aging and disease, direct
      neuropathological staining and immunohistochemistry, were used to quantify the
      structural integrity of the microvasculature and its innervation in three oldest
      old cohorts: 1) nonagenarians with AD and a high amyloid plaque load; 2)
      nonagenarians with no dementia and a high amyloid plaque load; 3) nonagenarians
      without dementia or amyloid plaques. In addition, a non-demented (ND) group
      (average age 71 years) with no amyloid plaques was included for comparison. While
      gray matter thickness and overall brain mass were reduced in AD compared to ND
      control groups, overall capillary density was not different. However, degenerated
      string capillaries were elevated in AD, potentially suggesting greater
      microvascular "dysfunction" compared to ND groups. Intriguingly, apolipoprotein
      epsilon4 carriers had significantly higher string vessel counts relative to non
      epsilon4 carriers. Taken together, these data suggest a concomitant loss of
      functional capillaries and brain volume in AD subjects. We also demonstrated a
      trend of decreasing vesicular acetylcholine transporter staining, a marker of
      cortical cholinergic afferents that contribute to arteriolar vasoregulation, in
      AD compared to ND control groups, suggesting impaired control of vasodilation in
      AD subjects. In addition, tyrosine hydroxylase, a marker of noradrenergic
      vascular innervation, was reduced which may also contribute to a loss of control
      of vasoconstriction. The data highlight the importance of the brain
      microcirculation in the pathogenesis and evolution of AD.

PMID- 22615836
TI  - Adaptive and bounded investment returns promote cooperation in spatial public
      goods games.
AB  - The public goods game is one of the most famous models for studying the evolution
      of cooperation in sizable groups. The multiplication factor in this game can
      characterize the investment return from the public good, which may be variable
      depending on the interactive environment in realistic situations. Instead of
      using the same universal value, here we consider that the multiplication factor
      in each group is updated based on the differences between the local and global
      interactive environments in the spatial public goods game, but meanwhile limited
      to within a certain range. We find that the adaptive and bounded investment
      returns can significantly promote cooperation. In particular, full cooperation
      can be achieved for high feedback strength when appropriate limitation is set for
      the investment return. Also, we show that the fraction of cooperators in the
      whole population can become larger if the lower and upper limits of the
      multiplication factor are increased. Furthermore, in comparison to the
      traditionally spatial public goods game where the multiplication factor in each
      group is identical and fixed, we find that cooperation can be better promoted if
      the multiplication factor is constrained to adjust between one and the group size
      in our model. Our results highlight the importance of the locally adaptive and
      bounded investment returns for the emergence and dominance of cooperative
      behavior in structured populations.

PMID- 22615837
TI  - The brain matures with stronger functional connectivity and decreased randomness
      of its network.
AB  - We investigated the development of the brain's functional connectivity throughout
      the life span (ages 5 through 71 years) by measuring EEG activity in a large
      population-based sample. Connectivity was established with Synchronization
      Likelihood. Relative randomness of the connectivity patterns was established with
      Watts and Strogatz' (1998) graph parameters C (local clustering) and L (global
      path length) for alpha (~10 Hz), beta (~20 Hz), and theta (~4 Hz) oscillation
      networks. From childhood to adolescence large increases in connectivity in alpha,
      theta and beta frequency bands were found that continued at a slower pace into
      adulthood (peaking at ~50 yrs). Connectivity changes were accompanied by
      increases in L and C reflecting decreases in network randomness or increased
      order (peak levels reached at ~18 yrs). Older age (55+) was associated with
      weakened connectivity. Semi-automatically segmented T1 weighted MRI images of 104
      young adults revealed that connectivity was significantly correlated to cerebral
      white matter volume (alpha oscillations: r = 33, p<01; theta: r = 22, p<05),
      while path length was related to both white matter (alpha: max. r = 38, p<001)
      and gray matter (alpha: max. r = 36, p<001; theta: max. r = 36, p<001) volumes.
      In conclusion, EEG connectivity and graph theoretical network analysis may be
      used to trace structural and functional development of the brain.

PMID- 22615838
TI  - Photic desynchronization of two subgroups of circadian oscillators in a network
      model of the suprachiasmatic nucleus with dispersed coupling strengths.
AB  - The suprachiasmatic nucleus (SCN) is the master circadian clock in mammals and is
      composed of thousands of neuronal oscillators expressing different intrinsic
      periods. These oscillators form a coupled network with a free-running period
      around 24 h in constant darkness and entrainable to the external light-dark cycle
      (T cycle). Coupling plays an important role in setting the period of the network
      and its range of entrainment. Experiments in rats have shown that two subgroups
      of oscillators within the SCN, a ventrolateral (VL) subgroup that receives photic
      input and a dorsomedial (DM) subgroup that is coupled to VL, can be
      desynchronized under a short (22-h) T cycle, with VL entrained to the cycle and
      DM free-running. We use a modified Goodwin model to understand how entrainment of
      the subgroups to short (22-h) and long (26-h) T cycles is influenced by light
      intensity, the proportion of neurons that receives photic input, and coupling
      heterogeneity. We find that the model's critical value for the proportion of
      photically-sensitive neurons is in accord with actual experimental estimates,
      while the model's inclusion of dispersed coupling can account for the
      experimental observation that VL and DM desynchronize more readily under the 22-h
      than under the 26-h T cycle. Heterogeneous intercellular coupling within the SCN
      is likely central to the generation of complex behavioral patterns.

PMID- 22615839
TI  - Failure to recognize nontuberculous mycobacteria leads to misdiagnosis of chronic
      pulmonary tuberculosis.
AB  - BACKGROUND: Nontuberculous mycobacterial (NTM) infections cause morbidity
      worldwide. They are difficult to diagnose in resource-limited regions, and most
      patients receive empiric treatment for tuberculosis (TB). Our objective here is
      to evaluate the potential impact of NTM diseases among patients treated
      presumptively for tuberculosis in Mali. METHODS: We re-evaluated sputum specimens
      among patients newly diagnosed with TB (naive) and those previously treated for
      TB disease (chronic cases). Sputum microscopy, culture and Mycobacterium
      tuberculosis drug susceptibility testing were performed. Identification of
      strains was performed using molecular probes or sequencing of secA1 and/or 16S
      rRNA genes. RESULTS: Of 142 patients enrolled, 61 (43%) were clinically
      classified as chronic cases and 17 (12%) were infected with NTM. Eleven of the
      142 (8%) patients had NTM disease alone (8 M. avium, 2 M. simiae and 1 M.
      palustre). All these 11 were from the chronic TB group, comprising 11/61 (18%) of
      that group and all were identified as candidates for second line treatment. The
      remaining 6/17 (35.30%) NTM infected patients had coinfection with M.
      tuberculosis and all 6 were from the TB treatment naive group. These 6 were
      candidates for the standard first line treatment regimen of TB. M. avium was
      identified in 11 of the 142 (8%) patients, only 3/11 (27.27%) of whom were HIV
      positive. CONCLUSIONS: NTM infections should be considered a cause of morbidity
      in TB endemic environments especially when managing chronic TB cases to limit
      morbidity and provide appropriate treatment.

PMID- 22615841
TI  - Tailored vs. standardized internet-based cognitive behavior therapy for
      depression and comorbid symptoms: a randomized controlled trial.
AB  - BACKGROUND AND AIMS: Major depression can be treated by means of cognitive
      behavior therapy, delivered via the Internet as guided self-help. Individually
      tailored guided self-help treatments have shown promising results in the
      treatment of anxiety disorders. This randomized controlled trial tested the
      efficacy of an Internet-based individually tailored guided self-help treatment
      which specifically targeted depression with comorbid symptoms. The treatment was
      compared both to standardized (non-tailored) Internet-based treatment and to an
      active control group in the form of a monitored online discussion group. Both
      guided self-help treatments were based on cognitive behavior therapy and lasted
      for 10 weeks. The discussion group consisted of weekly discussion themes related
      to depression and the treatment of depression. METHODS: A total of 121
      participants with diagnosed major depressive disorder and with a range of
      comorbid symptoms were randomized to three groups. The tailored treatment
      consisted of a prescribed set of modules targeting depression as well as comorbid
      problems. The standardized treatment was a previously tested guided self-help
      program for depression. RESULTS: From pre-treatment to post-treatment, both
      treatment groups improved on measures of depression, anxiety and quality of life.
      The results were maintained at a 6-month follow-up. Subgroup analyses showed that
      the tailored treatment was more effective than the standardized treatment among
      participants with higher levels of depression at baseline and more comorbidity,
      both in terms of reduction of depressive symptoms and on recovery rates. In the
      subgroup with lower baseline scores of depression, few differences were seen
      between treatments and the discussion group. CONCLUSIONS: This study shows that
      tailored Internet-based treatment for depression is effective and that addressing
      comorbidity by tailoring may be one way of making guided self-help treatments
      more effective than standardized approaches in the treatment of more severe
      depression. TRIAL REGISTRATION: Clinicaltrials.gov NCT01181583.

PMID- 22615840
TI  - Overexpression of CARMA3 in non-small-cell lung cancer is linked for tumor
      progression.
AB  - We aimed to investigate the clinical significance of the expression of novel
      scaffold protein CARMA3 in non-small-cell lung cancer (NSCLC) and the biological
      function of CARMA3 in NSCLC cell lines. We observed moderate to high CARMA3
      staining in 68.8% of 141 NSCLC specimens compared to corresponding normal
      tissues. The overexpression of CARMA3 was significantly correlated with TNM stage
      (P = 0.022) and tumor status (P = 0.013). CARMA3 upregulation also correlated
      with a shorter survival rate of patients of nodal status N0 (P = 0.042)as well as
      the expression of epidermal growth factor receptor (EGFR) (P = 0.009). In EGFR
      mutation positive cases, CARMA3 expression was much higher (87.5%) compared to
      non-mutation cases (66.1%). In addition, we observed that knockdown of CARMA3
      inhibits tumor cell proliferation and invasion, and induces cell cycle arrest at
      the boundary between the G1 and S phase. We further demonstrated a direct link
      between CARMA3 and NF-kappaB activation. The change of biological behavior in
      CARMA3 knockdown cells may be NF-kappaB-related. Our findings demonstrated, for
      the first time, that CARMA3 was overexpressed in NSCLC and correlated with lung
      cancer progression, EGFR expression, and EGFR mutation. CARMA3 could serve as a
      potential companion drug target, along with NF-kB and EGFR in EGFR-mutant lung
      cancers.

PMID- 22615842
TI  - Modified laminar bone in Ampelosaurus atacis and other Titanosaurs (Sauropoda):
      implications for life history and physiology.
AB  - BACKGROUND: Long bone histology of the most derived Sauropoda, the Titanosauria
      suggests that titanosaurian long bone histology differs from the uniform bone
      histology of basal Sauropoda. Here we describe the long bone histology of the
      titanosaur Ampelosaurus atacis and compare it to that of basal neosauropods and
      other titanosaurs to clarify if a special titanosaur bone histology exists.
      METHODOLOGY/PRINCIPAL FINDINGS: Ampelosaurus retains the laminar vascular
      organization of basal Sauropoda, but throughout most of cortical growth, the
      scaffolding of the fibrolamellar bone, which usually is laid down as matrix of
      woven bone, is laid down as parallel-fibered or lamellar bone matrix instead. The
      remodeling process by secondary osteons is very extensive and overruns the
      periosteal bone deposition before skeletal maturity is reached. Thus, no EFS is
      identifiable. Compared to the atypical bone histology of Ampelosaurus, the large
      titanosaur Alamosaurus shows typical laminar fibrolamellar bone. The titanosaurs
      Phuwiangosaurus, Lirainosaurus, and Magyarosaurus, although differing in certain
      features, all show this same low amount or absence of woven bone from the
      scaffolding of the fibrolamellar bone, indicating a clear reduction in growth
      rate resulting in a higher bone tissue organization. To describe the peculiar
      primary cortical bone tissue of Phuwiangosaurus, Ampelosaurus, Lirainosaurus, and
      Magyarosaurus, we here introduce a new term, "modified laminar bone" (MLB).
      CONCLUSIONS/SIGNIFICANCE: Importantly, MLB is as yet not known from extant
      animals. At least in Lirainosaurus and Magyarosaurus the reduction of growth rate
      indicated by MLB is coupled with a drastic body size reduction and maybe also a
      reduction in metabolic rate, interpreted as a result of dwarfing on the European
      islands during the Late Cretaceous. Phuwiangosaurus and Ampelosaurus both show a
      similar reduction in growth rate but not in body size, possibly indicating also a
      reduced metabolic rate. The large titanosaur Alamosaurus, on the other hand,
      retained the plesiomorphic bone histology of basal neosauropods.

PMID- 22615843
TI  - Interferon-beta induces cellular senescence in cutaneous human papilloma virus
      transformed human keratinocytes by affecting p53 transactivating activity.
AB  - Interferon (IFN)-beta inhibits cell proliferation and affects cell cycle in
      keratinocytes transformed by both mucosal high risk Human Papilloma Virus (HPV)
      and cutaneous HPV E6 and E7 proteins. In particular, upon longer IFN-beta
      treatments, cutaneous HPV38 expressing cells undergo senescence. IFN-beta appears
      to induce senescence by upregulating the expression of the tumor suppressor PML,
      a well known IFN-induced gene. Indeed, experiments in gene silencing via specific
      siRNAs have shown that PML is essential in the execution of the senescence
      programme and that both p53 and p21 pathways are involved. IFN-beta treatment
      leads to a modulation of p53 phosphorylation and acetylation status and a
      reduction in the expression of the p53 dominant negative DeltaNp73. These effects
      allow the recovery of p53 transactivating activity of target genes involved in
      the control of cell proliferation. Taken together, these studies suggest that
      signaling through the IFN pathway might play an important role in cellular
      senescence. This additional understanding of IFN antitumor action and mechanisms
      influencing tumor responsiveness or resistance appears useful in aiding further
      promising development of biomolecular strategies in the IFN therapy of cancer.

PMID- 22615844
TI  - HBsAg inhibits the translocation of JTB into mitochondria in HepG2 cells and
      potentially plays a role in HCC progression.
AB  - BACKGROUND AND AIMS: The expression of the jumping translocation breakpoint (JTB)
      gene is upregulated in malignant liver tissues; however, JTB is associated with
      unbalanced translocations in many other types of cancer that suppress JTB
      expression. No comprehensive analysis on its function in human hepatocellular
      carcinoma (HCC) has been performed to date. We aimed to define the biological
      consequences for interaction between JTB and HBsAg in HCC cell lines. METHODS: We
      employed the stable transfection to establish small HBsAg expressing HepG2 cell
      line, and stably silenced the JTB expression using short hairpin RNA in HepG2
      cell line. The effects of JTB and small HBsAg in vitro were determined by
      assessing cell apoptosis and motility. RESULTS: Silencing of JTB expression
      promoted cancer cell motility and reduced cell apoptosis, which was significantly
      enhanced by HBs expression. Expression of HBsAg inhibited the translocation of
      JTB to the mitochondria. Furthermore, silencing of the JTB resulted in an
      increase in the phosphorylation of p65 in HepG2 cells and HepG2-HBs cells,
      whereas HBsAg expression decreased the phosphorylation of p65. The silencing of
      JTB in HepG2-HBs cells conferred increased advantages in cell motility and anti
      apoptosis. CONCLUSION: HBsAg inhibited the translocation of JTB to the
      mitochondria and decreased the phosphorylation of p65 through the interaction
      with JTB, After JTB knockdown, HBsAg exhibited a stronger potential to promote
      tumor progression. Our data suggested that JTB act as a tumor suppressor gene in
      regards to HBV infection and its activation might be applied as a therapeutic
      strategy for in control of HBV related HCC development.

PMID- 22615845
TI  - VIP deficient mice exhibit resistance to lipopolysaccharide induced endotoxemia
      with an intrinsic defect in proinflammatory cellular responses.
AB  - Vasoactive intestinal peptide (VIP) is a pleiotropic neuropeptide with
      immunomodulatory properties. The administration of this peptide has been shown to
      have beneficial effects in murine models of inflammatory diseases including
      septic shock, rheumatoid arthritis, multiple sclerosis (MS) and Crohn's disease.
      However, the role of the endogenous peptide in inflammatory disease remains
      obscure because VIP-deficient mice were recently found to exhibit profound
      resistance in a model of MS. In the present study, we analyzed the response of
      female VIP deficient (KO) mice to intraperitoneal lipopolysaccharide (LPS)
      administration. We observed significant resistance to LPS in VIP KO mice, as
      evidenced by lower mortality and reduced tissue damage. The increased survival
      was associated with decreased levels of proinflammatory cytokines (TNFalpha, IL-6
      and IL-12) in sera and peritoneal suspensions of these mice. Moreover, the
      expression of TNFalpha and IL-6 mRNA was reduced in peritoneal cells, spleens and
      lungs from LPS-treated VIP KO vs. WT mice, suggesting that the resistance might
      be mediated by an intrinsic defect in the responsiveness of immune cells to
      endotoxin. In agreement with this hypothesis, peritoneal cells isolated from VIP
      KO naive mice produced lower levels of proinflammatory cytokines in response to
      LPS in vitro. Finally, decreased NF-kappaB pathway activity in peritoneal cells
      was observed both in vivo and in vitro, as determined by assay of phosphorylated
      I-kappaB. The results demonstrate that female VIP KO mice exhibit resistance to
      LPS-induced shock, explainable in part by the presence of an intrinsic defect in
      the responsiveness of inflammatory cells to endotoxin.

PMID- 22615846
TI  - Shape self-regulation in early lung morphogenesis.
AB  - The arborescent architecture of mammalian conductive airways results from the
      repeated branching of lung endoderm into surrounding mesoderm. Subsequent lung's
      striking geometrical features have long raised the question of developmental
      mechanisms involved in morphogenesis. Many molecular actors have been identified,
      and several studies demonstrated the central role of Fgf10 and Shh in growth and
      branching. However, the actual branching mechanism and the way branching events
      are organized at the organ scale to achieve a self-avoiding tree remain to be
      understood through a model compatible with evidenced signaling. In this paper we
      show that the mere diffusion of FGF10 from distal mesenchyme involves
      differential epithelial proliferation that spontaneously leads to branching.
      Modeling FGF10 diffusion from sub-mesothelial mesenchyme where Fgf10 is known to
      be expressed and computing epithelial and mesenchymal growth in a coupled manner,
      we found that the resulting laplacian dynamics precisely accounts for the
      patterning of FGF10-induced genes, and that it spontaneously involves
      differential proliferation leading to a self-avoiding and space-filling tree,
      through mechanisms that we detail. The tree's fine morphological features depend
      on the epithelial growth response to FGF10, underlain by the lung's complex
      regulatory network. Notably, our results suggest that no branching information
      has to be encoded and that no master routine is required to organize branching
      events at the organ scale. Despite its simplicity, this model identifies key
      mechanisms of lung development, from branching to organ-scale organization, and
      could prove relevant to the development of other branched organs relying on
      similar pathways.

PMID- 22615847
TI  - Association analysis of the extended MHC region in celiac disease implicates
      multiple independent susceptibility loci.
AB  - Celiac disease is a common autoimmune disease caused by sensitivity to the
      dietary protein gluten. Forty loci have been implicated in the disease. All
      disease loci have been characterized as low-penetrance, with the exception of the
      high-risk genotypes in the HLA-DQA1 and HLA-DQB1 genes, which are necessary but
      not sufficient to cause the disease. The very strong effects from the known HLA
      loci and the genetically complex nature of the major histocompatibility complex
      (MHC) have precluded a thorough investigation of the region. The purpose of this
      study was to test the hypothesis that additional celiac disease loci exist within
      the extended MHC (xMHC). A set of 1898 SNPs was analyzed for association across
      the 7.6 Mb xMHC region in 1668 confirmed celiac disease cases and 517 unaffected
      controls. Conditional recursive partitioning was used to create an informative
      indicator of the known HLA-DQA1 and HLA-DQB1 high-risk genotypes that was
      included in the association analysis to account for their effects. A linkage
      disequilibrium-based grouping procedure was utilized to estimate the number of
      independent celiac disease loci present in the xMHC after accounting for the
      known effects. There was significant statistical evidence for four new
      independent celiac disease loci within the classic MHC region. This study is the
      first comprehensive association analysis of the xMHC in celiac disease that
      specifically accounts for the known HLA disease genotypes and the genetic
      complexity of the region.

PMID- 22615848
TI  - Procalcitonin predicts response to beta-lactam treatment in hospitalized children
      with community-acquired pneumonia.
AB  - BACKGROUND: Antibiotic treatment of community-acquired pneumonia (CAP) in
      children remains mostly empirical because clinical and paraclinical findings
      poorly discriminate the principal causes of CAP. Fast response to beta-lactam
      treatment can be considered a proxy of pneumococcal aetiology. We aimed to
      identify the best biological predictor of response to beta-lactam therapy in
      children hospitalized for CAP. METHODS: A retrospective, single-centre cohort
      study included all consecutive patients 1 month to 16 years old hospitalized in a
      teaching hospital in Paris, France, because of CAP empirically treated with a
      beta-lactam alone from 2003 to 2010. Uni- and multivariate analyses were used to
      study the ability of routine biological parameters available in the Emergency
      Department to predict a favourable response to beta-lactam (defined as apyrexia
      within 48 hours of treatment onset). RESULTS: Among the 125 included patients,
      85% (106) showed a favourable response to beta-lactam. In multivariate logistic
      regression, we found procalcitonin (PCT) the only independent predictor of
      apyrexia (p = 0.008). The adjusted odds ratio for the decadic logarithm of PCT
      was 4.3 (95% CI 1.5-12.7). At >= 3 ng/mL, PCT had 55.7% sensitivity (45.7-65.3),
      78.9% specificity (54.4-93.9), 93.7% positive predictive value (84.5-98.2), 24.2%
      negative predictive value (14.2-36.7), 2.64 positive likelihood ratio (1.09-6.42)
      and 0.56 negative likelihood ratio (0.41-0.77). In the 4 children with a PCT
      level >= 3 ng/mL and who showed no response to beta-lactam treatment, secondary
      pleural effusion had developed in 3, and viral co-infection was documented in 1.
      CONCLUSIONS: PCT is the best independent biologic predictor of favourable
      response to beta-lactam therapy in children hospitalized for CAP. Thus, a high
      PCT level is highly suggestive of pneumococcal aetiology. However, a 3-ng/mL cut
      off does not seem compatible with daily medical practice, and additional research
      is needed to further define the role of PCT in managing CAP in children.

PMID- 22615849
TI  - Measures of anxiety in zebrafish (Danio rerio): dissociation of black/white
      preference and novel tank test.
AB  - The effects of wall color stimuli on diving, and the effects of depth stimuli on
      scototaxis, were assessed in zebrafish. Three groups of fish were confined to a
      black, a white, or a transparent tank, and tested for depth preference. Two
      groups of fish were confined to a deep or a shallow tank, and tested for black
      white preference. As predicted, fish preferred the deep half of a split-tank over
      the shallow half, and preferred the black half of a black/white tank over the
      white half. Results indicated that the tank wall color significantly affected
      depth preference, with the transparent tank producing the strongest depth
      preference and the black tank producing the weakest preference. Tank depth,
      however, did not significantly affect color preference. Additionally, wall color
      significantly affected shuttling and immobility, while depth significantly
      affected shuttling and thigmotaxis. These results are consistent with previous
      indications that the diving response and scototaxis may reflect dissociable
      mechanisms of behavior. We conclude that the two tests are complementary rather
      than interchangeable, and that further research on the motivational systems
      underlying behavior in each of the two tests is needed.

PMID- 22615850
TI  - Dark or short nights: differential latitudinal constraints in nestling
      provisioning patterns of a nocturnally hunting bird species.
AB  - In diurnal bird species, individuals breeding at high latitudes have larger
      broods than at lower latitudes, which has been linked to differences in the daily
      time available for foraging. However, it remains unclear how latitude is linked
      with parental investment in nocturnal species. Here, we investigate nestling
      provisioning rates of male Tengmalm's owls in two populations at different
      latitudes (Czech Republic 50  degrees N; Finland 63  degrees N) with the help of
      cameras integrated into nest boxes. Clutch sizes were smaller in the Czech
      population (CZ: 5.1 +/- 0.1; FIN: 6.6 +/- 0.1), but given the higher nestling
      mortality in the Finnish population, the number of fledglings did not differ
      between the two populations (CZ: 3.5 +/- 0.3; FIN: 3.9 +/- 0.2). Nestling
      provisioning patterns varied within days, over the reproductive season and
      between the two sites. Males delivered most food at dusk and dawn, having peak
      delivery rates at sun angles of -11 degrees  to -15 degrees  at both sites, and
      males increased the prey delivery rates with higher nestling requirements. Given
      the longer nights during summer in the Czech Republic compared to Finland, Czech
      males only showed a small shift in their delivery peak during the night from -17
      degrees  in April to -14 degrees  in July. In contrast, Finnish males shifted
      their peak of prey delivery from -11 degrees  in April to -1 degrees  in July.
      Consequently, Czech males had a longer hunting time per night around midsummer
      when feeding young (360 min) than Finnish males (270 min). This suggests that
      nocturnal owl species in northern populations are constrained by the short nights
      during the breeding season, which can limit the number of young they can raise.
      Moreover, owls in northern populations are additionally constrained through the
      unpredictable changes in food availability between years, and both these factors
      are likely to influence the reproductive investment between populations.

PMID- 22615851
TI  - Transcriptome characterization by RNA-seq unravels the mechanisms of butyrate
      induced epigenomic regulation in bovine cells.
AB  - Short-chain fatty acids (SCFAs), especially butyrate, affect cell
      differentiation, proliferation, and motility. Butyrate also induces cell cycle
      arrest and apoptosis through its inhibition of histone deacetylases (HDACs). In
      addition, butyrate is a potent inducer of histone hyper-acetylation in cells.
      Therefore, this SCFA provides an excellent in vitro model for studying the
      epigenomic regulation of gene expression induced by histone acetylation. In this
      study, we analyzed the differential in vitro expression of genes induced by
      butyrate in bovine epithelial cells by using deep RNA-sequencing technology (RNA
      seq). The number of sequences read, ranging from 57,303,693 to 78,933,744, were
      generated per sample. Approximately 11,408 genes were significantly impacted by
      butyrate, with a false discovery rate (FDR) <0.05. The predominant cellular
      processes affected by butyrate included cell morphological changes, cell cycle
      arrest, and apoptosis. Our results provided insight into the transcriptome
      alterations induced by butyrate, which will undoubtedly facilitate our
      understanding of the molecular mechanisms underlying butyrate-induced epigenomic
      regulation in bovine cells.

PMID- 22615852
TI  - IL-1beta is upregulated in the diabetic retina and retinal vessels: cell-specific
      effect of high glucose and IL-1beta autostimulation.
AB  - Many molecular and cellular abnormalities detected in the diabetic retina support
      a role for IL-1beta-driven neuroinflammation in the pathogenesis of diabetic
      retinopathy. IL-1beta is well known for its role in the induction and, through
      autostimulation, amplification of neuroinflammation. Upregulation of IL-1beta has
      been consistently detected in the diabetic retina; however, the mechanisms and
      cellular source of IL-1beta overexpression are poorly understood. The aim of this
      study was to investigate the effect of high glucose and IL-1beta itself on IL
      1beta expression in microglial, macroglial (astrocytes and Muller cells) and
      retinal vascular endothelial cells; and to study the effect of diabetes on the
      expression of IL-1beta in isolated retinal vessels and on the temporal pattern of
      IL-1beta upregulation and glial reactivity in the retina of streptozotocin
      diabetic rats. IL-1beta was quantified by RealTime RT-PCR and ELISA, glial
      fibrillar acidic protein, alpha2-macroglobulin, and ceruloplasmin by
      immunoblotting. We found that high glucose induced a 3-fold increase of IL-1beta
      expression in retinal endothelial cells but not in macroglia and microglia. IL
      1beta induced its own synthesis in endothelial and macroglial cells but not in
      microglia. In retinal endothelial cells, the high glucose-induced IL-1beta
      overexpression was prevented by calphostin C, a protein kinase C inhibitor. The
      retinal vessels of diabetic rats showed increased IL-1beta expression as compared
      to non-diabetic rats. Retinal expression of IL-1beta increased early after the
      induction of diabetes, continued to increase with progression of the disease, and
      was temporally associated with upregulation of markers of glial activation. These
      findings point to hyperglycemia as the trigger and to the endothelium as the
      origin of the initial retinal upregulation of IL-1beta in diabetes; and to IL
      1beta itself, via autostimulation in endothelial and macroglial cells, as the
      mechanism of sustained IL-1beta overexpression. Interrupting the vicious circle
      triggered by IL-1beta autostimulation could limit the progression of diabetic
      retinopathy.

PMID- 22615853
TI  - The sound of feelings: electrophysiological responses to emotional speech in
      alexithymia.
AB  - BACKGROUND: Alexithymia is a personality trait characterized by difficulties in
      the cognitive processing of emotions (cognitive dimension) and in the experience
      of emotions (affective dimension). Previous research focused mainly on visual
      emotional processing in the cognitive alexithymia dimension. We investigated the
      impact of both alexithymia dimensions on electrophysiological responses to
      emotional speech in 60 female subjects. METHODOLOGY: During unattended
      processing, subjects watched a movie while an emotional prosody oddball paradigm
      was presented in the background. During attended processing, subjects detected
      deviants in emotional prosody. The cognitive alexithymia dimension was associated
      with a left-hemisphere bias during early stages of unattended emotional speech
      processing, and with generally reduced amplitudes of the late P3 component during
      attended processing. In contrast, the affective dimension did not modulate
      unattended emotional prosody perception, but was associated with reduced P3
      amplitudes during attended processing particularly to emotional prosody spoken in
      high intensity. CONCLUSIONS: Our results provide evidence for a dissociable
      impact of the two alexithymia dimensions on electrophysiological responses during
      the attended and unattended processing of emotional prosody. The observed
      electrophysiological modulations are indicative of a reduced sensitivity to the
      emotional qualities of speech, which may be a contributing factor to problems in
      interpersonal communication associated with alexithymia.

PMID- 22615854
TI  - Fatigue in patients with lung cancer is related with accelerated tryptophan
      breakdown.
AB  - BACKGROUND: Patients with cancer often suffer from fatigue and decreased quality
      of life which might be related to the breakdown of essential amino acid
      tryptophan. METHODS: In 50 patients with lung cancer we examined fatigue and the
      deterioration of quality of life in patients using the Functional Assessment of
      Cancer Therapy Anemia (FACT-An) and -Fatigue (FACT-F) subscales of FACT-General
      and the Mental adjustment to Cancer (MAC) questionnaires. Results were compared
      with tryptophan breakdown as well as serum concentrations of immune activation
      markers. RESULTS: Scores of psychological tests correlated significantly with
      tryptophan breakdown and with circulatory markers of inflammation. However,
      immune activation and tryptophan breakdown were not related to MAC scores.
      CONCLUSIONS: Tryptophan breakdown relates with fatigue and impaired quality of
      life in patients with lung cancer, while declining tryptophan levels are not
      associated with patients'coping strategies.

PMID- 22615855
TI  - A neuromorphic architecture for object recognition and motion anticipation using
      burst-STDP.
AB  - In this work we investigate the possibilities offered by a minimal framework of
      artificial spiking neurons to be deployed in silico. Here we introduce a
      hierarchical network architecture of spiking neurons which learns to recognize
      moving objects in a visual environment and determine the correct motor output for
      each object. These tasks are learned through both supervised and unsupervised
      spike timing dependent plasticity (STDP). STDP is responsible for the
      strengthening (or weakening) of synapses in relation to pre- and post-synaptic
      spike times and has been described as a Hebbian paradigm taking place both in
      vitro and in vivo. We utilize a variation of STDP learning, called burst-STDP,
      which is based on the notion that, since spikes are expensive in terms of energy
      consumption, then strong bursting activity carries more information than single
      (sparse) spikes. Furthermore, this learning algorithm takes advantage of
      homeostatic renormalization, which has been hypothesized to promote memory
      consolidation during NREM sleep. Using this learning rule, we design a spiking
      neural network architecture capable of object recognition, motion detection,
      attention towards important objects, and motor control outputs. We demonstrate
      the abilities of our design in a simple environment with distractor objects,
      multiple objects moving concurrently, and in the presence of noise. Most
      importantly, we show how this neural network is capable of performing these tasks
      using a simple leaky-integrate-and-fire (LIF) neuron model with binary synapses,
      making it fully compatible with state-of-the-art digital neuromorphic hardware
      designs. As such, the building blocks and learning rules presented in this paper
      appear promising for scalable fully neuromorphic systems to be implemented in
      hardware chips.

PMID- 22615856
TI  - Enzymatic activities and DNA substrate specificity of Mycobacterium tuberculosis
      DNA helicase XPB.
AB  - XPB, also known as ERCC3 and RAD25, is a 3' -> 5' DNA repair helicase belonging
      to the superfamily 2 of helicases. XPB is an essential core subunit of the
      eukaryotic basal transcription factor complex TFIIH. It has two well-established
      functions: in the context of damaged DNA, XPB facilitates nucleotide excision
      repair by unwinding double stranded DNA (dsDNA) surrounding a DNA lesion; while
      in the context of actively transcribing genes, XPB facilitates initiation of RNA
      polymerase II transcription at gene promoters. Human and other eukaryotic XPB
      homologs are relatively well characterized compared to conserved homologs found
      in mycobacteria and archaea. However, more insight into the function of bacterial
      helicases is central to understanding the mechanism of DNA metabolism and
      pathogenesis in general. Here, we characterized Mycobacterium tuberculosis XPB
      (Mtb XPB), a 3'->5' DNA helicase with DNA-dependent ATPase activity. Mtb XPB
      efficiently catalyzed DNA unwinding in the presence of significant excess of
      enzyme. The unwinding activity was fueled by ATP or dATP in the presence of
      Mg(2+)/Mn(2+). Consistent with the 3'->5' polarity of this bacterial XPB
      helicase, the enzyme required a DNA substrate with a 3' overhang of 15
      nucleotides or more. Although Mtb XPB efficiently unwound DNA model substrates
      with a 3' DNA tail, it was not active on substrates containing a 3' RNA tail. We
      also found that Mtb XPB efficiently catalyzed ATP-independent annealing of
      complementary DNA strands. These observations significantly enhance our
      understanding of the biological roles of Mtb XPB.

PMID- 22615857
TI  - Dynamic compression of chondrocyte-agarose constructs reveals new candidate
      mechanosensitive genes.
AB  - Articular cartilage is physiologically exposed to repeated loads. The mechanical
      properties of cartilage are due to its extracellular matrix, and homeostasis is
      maintained by the sole cell type found in cartilage, the chondrocyte. Although
      mechanical forces clearly control the functions of articular chondrocytes, the
      biochemical pathways that mediate cellular responses to mechanical stress have
      not been fully characterised. The aim of our study was to examine early molecular
      events triggered by dynamic compression in chondrocytes. We used an experimental
      system consisting of primary mouse chondrocytes embedded within an agarose
      hydrogel; embedded cells were pre-cultured for one week and subjected to short
      term compression experiments. Using Western blots, we demonstrated that
      chondrocytes maintain a differentiated phenotype in this model system and
      reproduce typical chondrocyte-cartilage matrix interactions. We investigated the
      impact of dynamic compression on the phosphorylation state of signalling
      molecules and genome-wide gene expression. After 15 min of dynamic compression,
      we observed transient activation of ERK1/2 and p38 (members of the mitogen
      activated protein kinase (MAPK) pathways) and Smad2/3 (members of the canonical
      transforming growth factor (TGF)-beta pathways). A microarray analysis performed
      on chondrocytes compressed for 30 min revealed that only 20 transcripts were
      modulated more than 2-fold. A less conservative list of 325 modulated genes
      included genes related to the MAPK and TGF-beta pathways and/or known to be
      mechanosensitive in other biological contexts. Of these candidate
      mechanosensitive genes, 85% were down-regulated. Down-regulation may therefore
      represent a general control mechanism for a rapid response to dynamic
      compression. Furthermore, modulation of transcripts corresponding to different
      aspects of cellular physiology was observed, such as non-coding RNAs or primary
      cilium. This study provides new insight into how chondrocytes respond to
      mechanical forces.

PMID- 22615858
TI  - Optic nerve head quantification in idiopathic intracranial hypertension by
      spectral domain OCT.
AB  - OBJECTIVE: To evaluate 3D spectral domain optical coherence tomography (SDOCT)
      volume scans as a tool for quantification of optic nerve head (ONH) volume as a
      potential marker for treatment effectiveness and disease progression in
      idiopathic intracranial hypertension (IIH). DESIGN AND PATIENTS: Cross-sectional
      pilot trial comparing 19 IIH patients and controls matched for gender, age and
      body mass index. Each participant underwent SDOCT. A custom segmentation
      algorithm was developed to quantify ONH volume (ONHV) and height (ONHH) in 3D
      volume scans. RESULTS: Whereas peripapillary retinal nerve fiber layer thickness
      did not show differences between controls and IIH patients, the newly developed
      3D parameters ONHV and ONHH were able to discriminate between controls, treated
      and untreated patients. Both ONHV and ONHH measures were related to levels of
      intracranial pressure (ICP). CONCLUSION: Our findings suggest 3D ONH measures as
      assessed by SDOCT as potential diagnostic and progression markers in IIH and
      other disorders with increased ICP. SDOCT may promise a fast and easy diagnostic
      alternative to repeated lumbar punctures and could therefore ease monitoring of
      treatment or disease progression.

PMID- 22615859
TI  - Computational and statistical analyses of amino acid usage and physico-chemical
      properties of the twelve late embryogenesis abundant protein classes.
AB  - Late Embryogenesis Abundant Proteins (LEAPs) are ubiquitous proteins expected to
      play major roles in desiccation tolerance. Little is known about their structure 
      function relationships because of the scarcity of 3-D structures for LEAPs. The
      previous building of LEAPdb, a database dedicated to LEAPs from plants and other
      organisms, led to the classification of 710 LEAPs into 12 non-overlapping classes
      with distinct properties. Using this resource, numerous physico-chemical
      properties of LEAPs and amino acid usage by LEAPs have been computed and
      statistically analyzed, revealing distinctive features for each class. This
      unprecedented analysis allowed a rigorous characterization of the 12 LEAP
      classes, which differed also in multiple structural and physico-chemical
      features. Although most LEAPs can be predicted as intrinsically disordered
      proteins, the analysis indicates that LEAP class 7 (PF03168) and probably LEAP
      class 11 (PF04927) are natively folded proteins. This study thus provides a
      detailed description of the structural properties of this protein family opening
      the path toward further LEAP structure - function analysis. Finally, since each
      LEAP class can be clearly characterized by a unique set of physico-chemical
      properties, this will allow development of software to predict proteins as LEAPs.

PMID- 22615860
TI  - The Fanconi anaemia components UBE2T and FANCM are functionally linked to
      nucleotide excision repair.
AB  - The many proteins that function in the Fanconi anaemia (FA) monoubiquitylation
      pathway initiate replicative DNA crosslink repair. However, it is not clear
      whether individual FA genes participate in DNA repair pathways other than
      homologous recombination and translesion bypass. Here we show that avian DT40
      cell knockouts of two integral FA genes--UBE2T and FANCM are unexpectedly
      sensitive to UV-induced DNA damage. Comprehensive genetic dissection experiments
      indicate that both of these FA genes collaborate to promote nucleotide excision
      repair rather than translesion bypass to protect cells form UV genotoxicity.
      Furthermore, UBE2T deficiency impacts on the efficient removal of the UV-induced
      photolesion cyclobutane pyrimidine dimer. Therefore, this work reveals that the
      FA pathway shares two components with nucleotide excision repair, intimating not
      only crosstalk between the two major repair pathways, but also potentially
      identifying a UBE2T-mediated ubiquitin-signalling response pathway that
      contributes to nucleotide excision repair.

PMID- 22615861
TI  - Phylogenomics of prokaryotic ribosomal proteins.
AB  - Archaeal and bacterial ribosomes contain more than 50 proteins, including 34 that
      are universally conserved in the three domains of cellular life (bacteria,
      archaea, and eukaryotes). Despite the high sequence conservation, annotation of
      ribosomal (r-) protein genes is often difficult because of their short lengths
      and biased sequence composition. We developed an automated computational pipeline
      for identification of r-protein genes and applied it to 995 completely sequenced
      bacterial and 87 archaeal genomes available in the RefSeq database. The pipeline
      employs curated seed alignments of r-proteins to run position-specific scoring
      matrix (PSSM)-based BLAST searches against six-frame genome translations,
      mitigating possible gene annotation errors. As a result of this analysis, we
      performed a census of prokaryotic r-protein complements, enumerated missing and
      paralogous r-proteins, and analyzed the distributions of ribosomal protein genes
      among chromosomal partitions. Phyletic patterns of bacterial and archaeal r
      protein genes were mapped to phylogenetic trees reconstructed from concatenated
      alignments of r-proteins to reveal the history of likely multiple independent
      gains and losses. These alignments, available for download, can be used as search
      profiles to improve genome annotation of r-proteins and for further comparative
      genomics studies.

PMID- 22615862
TI  - The therapeutic effect of memantine through the stimulation of synapse formation
      and dendritic spine maturation in autism and fragile X syndrome.
AB  - Although the pathogenic mechanisms that underlie autism are not well understood,
      there is evidence showing that metabotropic and ionotropic glutamate receptors
      are hyper-stimulated and the GABAergic system is hypo-stimulated in autism.
      Memantine is an uncompetitive antagonist of NMDA receptors and is widely
      prescribed for treatment of Alzheimer's disease treatment. Recently, it has been
      shown to improve language function, social behavior, and self-stimulatory
      behaviors of some autistic subjects. However the mechanism by which memantine
      exerts its effect remains to be elucidated. In this study, we used cultured
      cerebellar granule cells (CGCs) from Fmr1 knockout (KO) mice, a mouse model for
      fragile X syndrome (FXS) and syndromic autism, to examine the effects of
      memantine on dendritic spine development and synapse formation. Our results show
      that the maturation of dendritic spines is delayed in Fmr1-KO CGCs. We also
      detected reduced excitatory synapse formation in Fmr1-KO CGCs. Memantine
      treatment of Fmr1-KO CGCs promoted cell adhesion properties. Memantine also
      stimulated the development of mushroom-shaped mature dendritic spines and
      restored dendritic spine to normal levels in Fmr1-KO CGCs. Furthermore, we
      demonstrated that memantine treatment promoted synapse formation and restored the
      excitatory synapses to a normal range in Fmr1-KO CGCs. These findings suggest
      that memantine may exert its therapeutic capacity through a stimulatory effect on
      dendritic spine maturation and excitatory synapse formation, as well as promoting
      adhesion of CGCs.

PMID- 22615863
TI  - Persistent hepatitis B viral replication in a FVB/N mouse model: impact of host
      and viral factors.
AB  - The mechanism underlying the chronicity of hepatitis B virus (HBV) infection has
      long been an interesting question. However, this mechanism remains unclear
      largely due to the lack of an animal model that can support persistent HBV
      replication and allow for the investigation of the relevant immune responses. In
      this study, we used hydrodynamic injection to introduce HBV replicon DNA into the
      livers of three different mouse strains: BALB/c, C57BL/6, and FVB/N.
      Interestingly, we found that an HBV clone persistently replicated in the livers
      of FVB/N mice for up to 50 weeks but was rapidly cleared from the livers of
      BALB/c and C57BL/6 mice. Flow cytometric analysis and quantitative reverse
      transcription PCR analysis of the mouse livers indicated that after DNA
      injection, FVB/N mice had few intrahepatic activated cytotoxic T lymphocytes
      (CTLs) and produced low levels of alanine aminotransferase, interferon (IFN)
      gamma, tumor necrosis factor (TNF)-alpha, and the CXCL9 and CXCL10 chemokines.
      These findings were in sharp contrast with those observed in BALB/c and C57BL/6
      mice, reflecting a strong correlation between the degree of liver inflammation
      and viral clearance. Mutational analysis further demonstrated that a change of
      Asn-214 to Ser-214 in the HBV surface antigen rendered the persistent HBV clone
      clearable in FVB/N mice, which was accompanied by increased levels of activated
      CTL and upregulated expression of IFN-gamma, CXCL9, and CXCL10 in the livers.
      These results indicate that the heterogeneity of the host factors and viral
      sequences may influence the immune responses against HBV. An inadequate
      activation of immune or inflammatory responses can lead to persistent HBV
      replication in vivo.

PMID- 22615864
TI  - Characterization of modular bacteriophage endolysins from Myoviridae phages OBP,
      201phi2-1 and PVP-SE1.
AB  - Peptidoglycan lytic enzymes (endolysins) induce bacterial host cell lysis in the
      late phase of the lytic bacteriophage replication cycle. Endolysins OBPgp279
      (from Pseudomonas fluorescens phage OBP), PVP-SE1gp146 (Salmonella enterica
      serovar Enteritidis phage PVP-SE1) and 201phi2-1gp229 (Pseudomonas chlororaphis
      phage 201phi2-1) all possess a modular structure with an N-terminal cell wall
      binding domain and a C-terminal catalytic domain, a unique property for
      endolysins with a Gram-negative background. All three modular endolysins showed
      strong muralytic activity on the peptidoglycan of a broad range of Gram-negative
      bacteria, partly due to the presence of the cell wall binding domain. In the case
      of PVP-SE1gp146, this domain shows a binding affinity for Salmonella
      peptidoglycan that falls within the range of typical cell adhesion molecules
      (K(aff) = 1.26 * 10(6) M(-1)). Remarkably, PVP-SE1gp146 turns out to be
      thermoresistant up to temperatures of 90  degrees C, making it a potential
      candidate as antibacterial component in hurdle technology for food preservation.
      OBPgp279, on the other hand, is suggested to intrinsically destabilize the outer
      membrane of Pseudomonas species, thereby gaining access to their peptidoglycan
      and exerts an antibacterial activity of 1 logarithmic unit reduction. Addition of
      0.5 mM EDTA significantly increases the antibacterial activity of the three
      modular endolysins up to 2-3 logarithmic units reduction. This research work
      offers perspectives towards elucidation of the structural differences explaining
      the unique biochemical and antibacterial properties of OBPgp279, PVP-SE1gp146 and
      201phi2-1gp229. Furthermore, these endolysins extensively enlarge the pool of
      potential antibacterial compounds used against multi-drug resistant Gram-negative
      bacterial infections.

PMID- 22615865
TI  - Grassland resistance and resilience after drought depends on management intensity
      and species richness.
AB  - The degree to which biodiversity may promote the stability of grasslands in the
      light of climatic variability, such as prolonged summer drought, has attracted
      considerable interest. Studies so far yielded inconsistent results and in
      addition, the effect of different grassland management practices on their
      response to drought remains an open question. We experimentally combined the
      manipulation of prolonged summer drought (sheltered vs. unsheltered sites), plant
      species loss (6 levels of 60 down to 1 species) and management intensity (4
      levels varying in mowing frequency and amount of fertilizer application).
      Stability was measured as resistance and resilience of aboveground biomass
      production in grasslands against decreased summer precipitation, where resistance
      is the difference between drought treatments directly after drought induction and
      resilience is the difference between drought treatments in spring of the
      following year. We hypothesized that (i) management intensification amplifies
      biomass decrease under drought, (ii) resistance decreases with increasing species
      richness and with management intensification and (iii) resilience increases with
      increasing species richness and with management intensification.We found that
      resistance and resilience of grasslands to summer drought are highly dependent on
      management intensity and partly on species richness. Frequent mowing reduced the
      resistance of grasslands against drought and increasing species richness
      decreased resistance in one of our two study years. Resilience was positively
      related to species richness only under the highest management treatment. We
      conclude that low mowing frequency is more important for high resistance against
      drought than species richness. Nevertheless, species richness increased
      aboveground productivity in all management treatments both under drought and
      ambient conditions and should therefore be maintained under future climates.

PMID- 22615866
TI  - Introduced pathogens and native freshwater biodiversity: a case study of
      Sphaerothecum destruens.
AB  - A recent threat to European fish diversity was attributed to the association
      between an intracellular parasite, Sphaerothecum destruens, and a healthy
      freshwater fish carrier, the invasive Pseudorasbora parva originating from China.
      The pathogen was found to be responsible for the decline and local extinction of
      the European endangered cyprinid Leucaspius delineatus and high mortalities in
      stocks of Chinook and Atlantic salmon in the USA. Here, we show that the emerging
      S. destruens is also a threat to a wider range of freshwater fish than originally
      suspected such as bream, common carp, and roach. This is a true generalist as an
      analysis of susceptible hosts shows that S. destruens is not limited to a
      phylogenetically narrow host spectrum. This disease agent is a threat to fish
      biodiversity as it can amplify within multiple hosts and cause high mortalities.

PMID- 22615867
TI  - Decoding the folding of Burkholderia glumae lipase: folding intermediates en
      route to kinetic stability.
AB  - The lipase produced by Burkholderia glumae folds spontaneously into an inactive
      near-native state and requires a periplasmic chaperone to reach its final active
      and secretion-competent fold. The B. glumae lipase-specific foldase (Lif) is
      classified as a member of the steric-chaperone family of which the propeptides of
      alpha-lytic protease and subtilisin are the best known representatives. Steric
      chaperones play a key role in conferring kinetic stability to proteins. However,
      until present there was no solid experimental evidence that Lif-dependent lipases
      are kinetically trapped enzymes. By combining thermal denaturation studies with
      proteolytic resistance experiments and the description of distinct folding
      intermediates, we demonstrate that the native lipase has a kinetically stable
      conformation. We show that a newly discovered molten globule-like conformation
      has distinct properties that clearly differ from those of the near-native
      intermediate state. The folding fingerprint of Lif-dependent lipases is put in
      the context of the protease-prodomain system and the comparison reveals clear
      differences that render the lipase-Lif systems unique. Limited proteolysis
      unveils structural differences between the near-native intermediate and the
      native conformation and sets the stage to shed light onto the nature of the
      kinetic barrier.

PMID- 22615868
TI  - The viral TRAF protein (ORF111L) from infectious spleen and kidney necrosis virus
      interacts with TRADD and induces caspase 8-mediated apoptosis.
AB  - Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the
      Megalocytivirus genus of the Iridoviridae family. It causes a serious and
      potentially pandemic disease in wild and cultured fishes. ISKNV infection induces
      evident apoptosis in mandarin fish (Siniperca chuatsi) and zebrafish (Danio
      renio). However, the mechanism is still unknown. After a genome-wide
      bioinformatics analysis of ISKNV-encoded proteins, the ISKNV open reading frame
      111L (ORF111L) shows a high similarity to the tumour necrosis factor receptor
      associated factor (TRAF) encoded by fish, mice and mammals, which is essential
      for apoptotic signal transduction. Moreover, ORF111L was verified to directly
      interact with the zebrafish TNF receptor type 1 associated death domain protein
      (TRADD). A recombinant plasmid containing the DNA sequence of ORF111L was
      constructed and microinjected into zebrafish embryos at the 1-2 cell stage to
      investigate its biological function in vivo. ORF111L overexpression in the
      embryos resulted in increased apoptosis. ORF111L-induced apoptosis was clearly
      associated with significant caspase 8 upregulation and activation. The knockdown
      of zebrafish caspase 8 expression effectively blocked the apoptosis induced by
      ORF111L overexpression. Significantly, ORF111L overexpression resulted in much
      stronger effect on caspase 8 and caspase 3 upregulation compared to zebrafish
      TRAF2. This is the first report of a viral protein similar to TRAF that interacts
      with TRADD and induces caspase 8-mediated apoptosis, which may provide novel
      insights into the pathogenesis of ISKNV infection.

PMID- 22615869
TI  - Species tree estimation for the late blight pathogen, Phytophthora infestans, and
      close relatives.
AB  - To better understand the evolutionary history of a group of organisms, an
      accurate estimate of the species phylogeny must be known. Traditionally, gene
      trees have served as a proxy for the species tree, although it was acknowledged
      early on that these trees represented different evolutionary processes.
      Discordances among gene trees and between the gene trees and the species tree are
      also expected in closely related species that have rapidly diverged, due to
      processes such as the incomplete sorting of ancestral polymorphisms. Recently,
      methods have been developed for the explicit estimation of species trees, using
      information from multilocus gene trees while accommodating heterogeneity among
      them. Here we have used three distinct approaches to estimate the species tree
      for five Phytophthora pathogens, including P. infestans, the causal agent of late
      blight disease in potato and tomato. Our concatenation-based "supergene" approach
      was unable to resolve relationships even with data from both the nuclear and
      mitochondrial genomes, and from multiple isolates per species. Our multispecies
      coalescent approach using both Bayesian and maximum likelihood methods was able
      to estimate a moderately supported species tree showing a close relationship
      among P. infestans, P. andina, and P. ipomoeae. The topology of the species tree
      was also identical to the dominant phylogenetic history estimated in our third
      approach, Bayesian concordance analysis. Our results support previous suggestions
      that P. andina is a hybrid species, with P. infestans representing one parental
      lineage. The other parental lineage is not known, but represents an independent
      evolutionary lineage more closely related to P. ipomoeae. While all five species
      likely originated in the New World, further study is needed to determine when and
      under what conditions this hybridization event may have occurred.

PMID- 22615870
TI  - Small-molecule synthetic compound norcantharidin reverses multi-drug resistance
      by regulating Sonic hedgehog signaling in human breast cancer cells.
AB  - Multi-drug resistance (MDR), an unfavorable factor compromising treatment
      efficacy of anticancer drugs, involves upregulated ATP binding cassette (ABC)
      transporters and activated Sonic hedgehog (Shh) signaling. By preparing human
      breast cancer MCF-7 cells resistant to doxorubicin (DOX), we examined the effect
      and mechanism of norcantharidin (NCTD), a small-molecule synthetic compound, on
      reversing multidrug resistance. The DOX-prepared MCF-7R cells also possessed
      resistance to vinorelbine, characteristic of MDR. At suboptimal concentration,
      NCTD significantly inhibited the viability of DOX-sensitive (MCF-7S) and DOX
      resistant (MCF-7R) cells and reversed the resistance to DOX and vinorelbine. NCTD
      increased the intracellular accumulation of DOX in MCF-7R cells and suppressed
      the upregulated the mdr-1 mRNA, P-gp and BCRP protein expression, but not the MRP
      1. The role of P-gp was strengthened by partial reversal of the DOX and
      vinorelbine resistance by cyclosporine A. NCTD treatment suppressed the
      upregulation of Shh expression and nuclear translocation of Gli-1, a hallmark of
      Shh signaling activation in the resistant clone. Furthermore, the Shh ligand
      upregulated the expression of P-gp and attenuated the growth inhibitory effect of
      NCTD. The knockdown of mdr-1 mRNA had not altered the expression of Shh and
      Smoothened in both MCF-7S and MCF-7R cells. This indicates that the role of Shh
      signaling in MDR might be upstream to mdr-1/P-gp, and similar effect was shown in
      breast cancer MDA-MB-231 and BT-474 cells. This study demonstrated that NCTD may
      overcome multidrug resistance through inhibiting Shh signaling and expression of
      its downstream mdr-1/P-gp expression in human breast cancer cells.

PMID- 22615871
TI  - N-terminal 1-54 amino acid sequence and Armadillo repeat domain are indispensable
      for P120-catenin isoform 1A in regulating E-cadherin.
AB  - P120-catenin (p120ctn) exerts important roles in regulating E-cadherin and
      invasiveness in cancer cells. However, the mechanisms by which p120ctn isoforms 1
      and 3 modulate E-cadherin expression are poorly understood. In the current study,
      HBE, H460, SPC and LTE cell lines were used to examine the effects of p120ctn
      isoforms 1A and 3A on E-cadherin expression and cell invasiveness. E-cadherin was
      localized on the cell membrane of HBE and H460 cells, while it was confined to
      the cytoplasm in SPC and LTE cells. Depletion of endogenous p120ctn resulted in
      reduced E-cadherin expression; however, p120ctn ablation showed opposite effects
      on invasiveness in the cell lines by decreasing invasiveness in SPC and LTE cells
      and increasing it in HBE and H460 cells. Restitution of 120ctn isoform 1A
      restored E-cadherin on the cell membrane and blocked cell invasiveness in H460
      and HBE cells, while it restored cytoplasmic E-cadherin and enhanced cell
      invasiveness in SPC and LTE cells. P120ctn isoform 3A increased the invasiveness
      in all four cell lines despite the lack of effect on E-cadherin expression,
      suggesting a regulatory pathway independent of E-cadherin. Moreover, five p120ctn
      isoform 1A deletion mutants were constructed and expressed in H460 and SPC cells.
      The results showed that only the M4 mutant, which contains N-terminal 1-54 amino
      acids and the Armadillo repeat domain, was functional in regulating E-cadherin
      and cell invasiveness, as observed in p120ctn isoform 1A. In conclusion, the N
      terminal 1-54 amino acid sequence and Armadillo repeat domain of p120ctn isoform
      1A are indispensable for regulating E-cadherin protein. P120ctn isoform 1A exerts
      opposing effects on cell invasiveness, corresponding to the subcellular
      localization of E-cadherin.

PMID- 22615872
TI  - Long interspersed nuclear element-1 hypomethylation and oxidative stress:
      correlation and bladder cancer diagnostic potential.
AB  - Although, increased oxidative stress and hypomethylation of long interspersed
      nuclear element-1 (LINE-1) associate with bladder cancer (BCa) development, the
      relationship between these alterations is unknown. We evaluated the oxidative
      stress and hypomethylation of the LINE-1 in 61 BCa patients and 45 normal
      individuals. To measure the methylation levels and to differentiate the LINE-1
      loci into hypermethylated, partially methylated and hypomethylated, peripheral
      blood cells, urinary exfoliated cells and cancerous tissues were evaluated by
      combined bisulfite restriction analysis PCR. The urinary total antioxidant status
      (TAS) and plasma protein carbonyl content were determined. The LINE-1 methylation
      levels and patterns, especially hypomethylated loci, in the blood and urine cells
      of the BCa patients were different from the levels and patterns in the healthy
      controls. The urinary TAS was decreased, whereas the plasma protein carbonyl
      content was increased in the BCa patients relative to the controls. A positive
      correlation between the methylation of LINE-1 in the blood-derived DNA and
      urinary TAS was found in both the BCa and control groups. The urinary
      hypomethylated LINE-1 loci and the plasma protein carbonyl content provided the
      best diagnostic potential for BCa prediction. Based on post-diagnostic samples,
      the combination test improved the diagnostic power to a sensitivity of 96% and a
      specificity of 96%. In conclusion, decreased LINE-1 methylation is associated
      with increased oxidative stress both in healthy and BCa subjects across the
      various tissue types, implying a dose-response association. Increases in the LINE
      1 hypomethylation levels and the number of hypomethylated loci in both the blood-
      and urine-derived cells and increase in the oxidative stress were found in the
      BCa patients. The combination test of the urinary hypomethylated LINE-1 loci and
      the plasma protein carbonyl content may be useful for BCa screening and
      monitoring of treatment.

PMID- 22615873
TI  - Social anxiety modulates subliminal affective priming.
AB  - BACKGROUND: It is well established that there is anxiety-related variation
      between observers in the very earliest, pre-attentive stage of visual processing
      of images such as emotionally expressive faces, often leading to enhanced
      attention to threat in a variety of disorders and traits. Whether there is also
      variation in early-stage affective (i.e. valenced) responses resulting from such
      images, however, is not yet known. The present study used the subliminal
      affective priming paradigm to investigate whether people varying in trait social
      anxiety also differ in their affective responses to very briefly presented,
      emotionally expressive face images. METHODOLOGY/PRINCIPAL FINDINGS: Participants
      (n = 67) completed a subliminal affective priming task, in which briefly
      presented and smiling, neutral and angry faces were shown for 10 ms durations
      (below objective and subjective thresholds for visual discrimination), and
      immediately followed by a randomly selected Chinese character mask (2000 ms).
      Ratings of participants' liking for each Chinese character indicated the degree
      of valenced affective response made to the unseen emotive images. Participants'
      ratings of their liking for the Chinese characters were significantly influenced
      by the type of face image preceding them, with smiling faces generating more
      positive ratings than neutral and angry ones (F(2,128) = 3.107, p<0.05). Self
      reported social anxiety was positively correlated with ratings of smiling
      relative to neutral-face primed characters (Pearson's r = .323, p<0.01).
      Individual variation in self-reported mood awareness was not associated with
      ratings. CONCLUSIONS: Trait social anxiety is associated with individual
      variation in affective responding, even in response to the earliest, pre
      attentive stage of visual image processing. However, the fact that these priming
      effects are limited to smiling and not angry (i.e. threatening) images leads us
      to propose that the pre-attentive processes involved in generating the subliminal
      affective priming effect may be different from those that generate attentional
      biases in anxious individuals.

PMID- 22615874
TI  - Transcriptional protein Sp1 regulates LEDGF transcription by directly interacting
      with its cis-elements in GC-rich region of TATA-less gene promoter.
AB  - LEDGF/p75 interacts with DNA/protein to regulate gene expression and function.
      Despite the recognized diversity of function of LEDGF/p75, knowledge of its
      transregulation is in its infancy. Here we report that LEDGF/p75 gene is TATA
      less, contains GC-rich cis elements and is transcriptionally regulated by Sp1
      involving small ubiquitin-like modifier (Sumo1). Using different cell lines, we
      showed that Sp1 overexpression increased the level of LEDGF/p75 protein and mRNA
      expression in a concentration-dependent fashion. In contrast, RNA interference
      depletion of intrinsic Sp1 or treatment with artemisinin, a Sp1 inhibitor,
      reduced expression of LEDGF/p75, suggesting Sp1-mediated regulation of LEDGF/p75.
      In silico analysis disclosed three evolutionarily conserved, putative Sp1 sites
      within LEDGF/p75 proximal promoter (-170/+1 nt). DNA-binding and transactivation
      assays using deletion and point mutation constructs of LEDGF/p75 promoter-CAT
      revealed that all Sp1 sites (-50/-43, -109/-102 and -146/-139) differentially
      regulate LEDGF/p75. Cotransfection studies with Sp1 in Drosophila cells that were
      Sp1-deficient, showed increased LEDGF/p75 transcription, while in lens epithelial
      cells (LECs) promoter activity was inhibited by artemisinin. These events were
      correlated with levels of endogenous Sp1-dependent LEDGF/p75 expression, and
      higher resistance to UVB-induced cell death. ChIP and transactivation assays
      showed that Sumoylation of Sp1 repressed its transcriptional activity as
      evidenced through its reduced binding to GC-box and reduced ability to activate
      LEDGF/p75 transcription. As whole, results revealed the importance of Sp1 in
      regulating expression of LEDGF/p75 gene and add to our knowledge of the factors
      that control LEDGF/p75 within cellular microenvironments, potentially providing a
      foundation for LEDGF/p75 expression-based transcription therapy.

PMID- 22615875
TI  - MENA is a transcriptional target of the Wnt/beta-catenin pathway.
AB  - Wnt/beta-catenin signalling pathway plays important roles in embryonic
      development and carcinogenesis. Overactivation of the pathway is one of the most
      common driving forces in major cancers such as colorectal and breast cancers. The
      downstream effectors of the pathway and its regulation of carcinogenesis and
      metastasis are still not very well understood. In this study, which was based on
      two genome-wide transcriptomics screens, we identify MENA (ENAH, Mammalian
      enabled homologue) as a novel transcriptional target of the Wnt/beta-catenin
      signalling pathway. We show that the expression of MENA is upregulated upon
      overexpression of degradation-resistant beta-catenin. Promoters of all mammalian
      MENA homologues contain putative binding sites for Tcf4 transcription factor--the
      primary effector of the Wnt/beta-catenin pathway and we demonstrate functionality
      of these Tcf4-binding sites using luciferase reporter assays and overexpression
      of beta-catenin, Tcf4 and dominant-negative Tcf4. In addition, lithium chloride
      mediated inhibition of GSK3beta also resulted in increase in MENA mRNA levels.
      Chromatin immunoprecipitation showed direct interaction between beta-catenin and
      MENA promoter in Huh7 and HEK293 cells and also in mouse brain and liver tissues.
      Moreover, overexpression of Wnt1 and Wnt3a ligands increased MENA mRNA levels.
      Additionally, knock-down of MENA ortholog in D. melanogaster eyeful and
      sensitized eye cancer fly models resulted in increased tumor and metastasis
      formations. In summary, our study identifies MENA as novel nexus for the Wnt/beta
      catenin and the Notch signalling cascades.

PMID- 22615876
TI  - Reduced gray to white matter tissue intensity contrast in schizophrenia.
AB  - BACKGROUND: While numerous structural magnetic resonance imaging (MRI) studies
      revealed changes of brain volume or density, cortical thickness and fibre
      integrity in schizophrenia, the effect of tissue alterations on the contrast
      properties of neural structures has so far remained mostly unexplored. METHODS:
      Whole brain high-resolution MRI at 3 Tesla was used to investigate tissue
      contrast and cortical thickness in patients with schizophrenia and healthy
      controls. RESULTS: Patients showed significantly decreased gray to white matter
      contrast in large portions throughout the cortical mantle with preponderance in
      inferior, middle, superior and medial temporal areas as well as in lateral and
      medial frontal regions. The extent of these intensity contrast changes exceeded
      the extent of cortical thinning. Further, contrast changes remained significant
      after controlling for cortical thickness measurements. CONCLUSIONS: Our findings
      clearly emphasize the presence of schizophrenia related brain tissue changes that
      alter the imaging properties of brain structures. Intensity contrast measurements
      might not only serve as a highly sensitive metric but also as a potential
      indicator of a distinct pathological process that might be independent from
      volume or thickness alterations.

PMID- 22615877
TI  - The adjuvanticity of an O. volvulus-derived rOv-ASP-1 protein in mice using
      sequential vaccinations and in non-human primates.
AB  - Adjuvants potentiate antigen-specific protective immune responses and can be key
      elements promoting vaccine effectiveness. We previously reported that the
      Onchocerca volvulus recombinant protein rOv-ASP-1 can induce activation and
      maturation of naive human DCs and therefore could be used as an innate adjuvant
      to promote balanced Th1 and Th2 responses to bystander vaccine antigens in mice.
      With a few vaccine antigens, it also promoted a Th1-biased response based on
      pronounced induction of Th1-associated IgG2a and IgG2b antibody responses and the
      upregulated production of Th1 cytokines, including IL-2, IFN-gamma, TNF-alpha and
      IL-6. However, because it is a protein, the rOv-ASP-1 adjuvant may also induce
      anti-self-antibodies. Therefore, it was important to verify that the host
      responses to self will not affect the adjuvanticity of rOv-ASP-1 when it is used
      in subsequent vaccinations with the same or different vaccine antigens. In this
      study, we have established rOv-ASP-1's adjuvanticity in mice during the course of
      two sequential vaccinations using two vaccine model systems: the receptor-binding
      domain (RBD) of SARS-CoV spike protein and a commercial influenza virus
      hemagglutinin (HA) vaccine comprised of three virus strains. Moreover, the
      adjuvanticity of rOv-ASP-1 was retained with an efficacy similar to that obtained
      when it was used for a first vaccination, even though a high level of anti-rOv
      ASP-1 antibodies was present in the sera of mice before the administration of the
      second vaccine. To further demonstrate its utility as an adjuvant for human use,
      we also immunized non-human primates (NHPs) with RBD plus rOv-ASP-1 and showed
      that rOv-ASP-1 could induce high titres of functional and protective anti-RBD
      antibody responses in NHPs. Notably, the rOv-ASP-1 adjuvant did not induce high
      titer antibodies against self in NHPs. Thus, the present study provided a sound
      scientific foundation for future strategies in the development of this novel
      protein adjuvant.

PMID- 22615879
TI  - The loss of functional caspase-12 in Europe is a pre-neolithic event.
AB  - BACKGROUND: Caspase-12 (CASP12) modulates the susceptibility to sepsis. In
      humans, the "C" allele at CASP12 rs497116 has been associated with an increased
      risk of sepsis. Instead, the derived "T" allele encodes for an inactive caspase
      12. Interestingly, Eurasians are practically fixed for the inactive variant,
      whereas in Sub-Saharan Africa the active variant is still common (~24%). This
      marked structure has been explained as a function of the selective advantage that
      the inactive caspase-12 confers by increasing resistance to infection. As regards
      to both when positive selection started acting and as to the speed with which
      fixation was achieved in Eurasia, estimates depend on the method and assumptions
      used, and can vary substantially. Using experimental evidence, we propose that,
      least in Eurasia, the increase in the frequency of the T allele might be related
      to the selective pressure exerted by the increase in zoonotic diseases
      transmission caused by the interplay between increased human population densities
      and a closer contact with animals during the Neolithic. METHODOLOG/PRINCIPAL
      FINDINGS: We genotyped CASP12 rs497116 in prehistoric individuals from 6
      archaeological sites from the North of the Iberian Peninsula that date from Late
      Upper Paleolithic to Late Neolithic. DNA extraction was done from teeth lacking
      cavities or breakages using standard anti-contamination procedures, including
      processing of the samples in a positive pressure, ancient DNA-only chamber,
      quantitation of DNAs by qPCR, duplication, replication, genotyping of associated
      animals, or cloning of PCR products. Out of 50, 24 prehistoric individuals could
      finally be genotyped for rs497116. Only the inactive form of CASP12 was found.
      CONCLUSIONS/SIGNIFICANCE: We demonstrate that the loss of caspase-12 in Europe
      predates animal domestication and that consequently CASP12 loss is unlikely to be
      related to the impact of zoonotic infections transmitted by livestock.

PMID- 22615878
TI  - Xenon and sevoflurane provide analgesia during labor and fetal brain protection
      in a perinatal rat model of hypoxia-ischemia.
AB  - It is not possible to identify all pregnancies at risk of neonatal hypoxic
      ischemic encephalopathy (HIE). Many women use some form of analgesia during
      childbirth and some anesthetic agents have been shown to be neuroprotective when
      used as analgesics at subanesthetic concentrations. In this study we sought to
      understand the effects of two anesthetic agents with presumptive analgesic
      activity and known preconditioning-neuroprotective properties (sevoflurane or
      xenon), in reducing hypoxia-induced brain damage in a model of intrauterine
      perinatal asphyxia. The analgesic and neuroprotective effects at subanesthetic
      levels of sevoflurane (0.35%) or xenon (35%) were tested in a rat model of
      intrauterine perinatal asphyxia. Analgesic effects were measured by assessing
      maternal behavior and spinal cord dorsal horn neuronal activation using c-Fos. In
      separate experiments, intrauterine fetal asphyxia was induced four hours after
      gas exposure; on post-insult day 3 apoptotic cell death was measured by caspase-3
      immunostaining in hippocampal neurons and correlated with the number of viable
      neurons on postnatal day (PND) 7. A separate cohort of pups was nurtured by a
      surrogate mother for 50 days when cognitive testing with Morris water maze was
      performed. Both anesthetic agents provided analgesia as reflected by a reduction
      in the number of stretching movements and decreased c-Fos expression in the
      dorsal horn of the spinal cord. Both agents also reduced the number of caspase-3
      positive (apoptotic) neurons and increased cell viability in the hippocampus at
      PND7. These acute histological changes were mirrored by improved cognitive
      function measured remotely after birth on PND 50 compared to control group.
      Subanesthetic doses of sevoflurane or xenon provided both analgesia and
      neuroprotection in this model of intrauterine perinatal asphyxia. These data
      suggest that anesthetic agents with neuroprotective properties may be effective
      in preventing HIE and should be tested in clinical trials in the future.

PMID- 22615880
TI  - Non-invasive quantification of white and brown adipose tissues and liver fat
      content by computed tomography in mice.
AB  - OBJECTIVES: Obesity and its distribution pattern are important factors for the
      prediction of the onset of diabetes in humans. Since several mouse models are
      suitable to study the pathophysiology of type 2 diabetes the aim was to validate
      a novel computed tomograph model (Aloka-Hitachi LCT-200) for the quantification
      of visceral, subcutaneous, brown and intrahepatic fat depots in mice. METHODS:
      Different lean and obese mouse models (C57BL/6, B6.V-Lep(ob), NZO) were used to
      determine the most adequate scanning parameters for the detection of the
      different fat depots. The data were compared with those obtained after
      preparation and weighing the fat depots. Liver fat content was determined by
      biochemical analysis. RESULTS: The correlations between weights of fat tissues on
      scale and weights determined by CT were significant for subcutaneous (r(2) =
      0.995), visceral (r(2) = 0.990) and total white adipose tissue (r(2) = 0.992).
      Moreover, scans in the abdominal region, between lumbar vertebrae L4 to L5
      correlated with whole-body fat distribution allowing experimenters to reduce
      scanning time and animal exposure to radiation and anesthesia. Test-retest
      reliability and measurements conducted by different experimenters showed a high
      reproducibility in the obtained results. Intrahepatic fat content estimated by CT
      was linearly related to biochemical analysis (r(2) = 0.915). Furthermore, brown
      fat mass correlated well with weighted brown fat depots (r(2) = 0.952). In
      addition, short-term cold-expose (4  degrees C, 4 hours) led to alterations in
      brown adipose tissue attributed to a reduction in triglyceride content that can
      be visualized as an increase in Hounsfield units by CT imaging. CONCLUSION: The
      3D imaging of fat by CT provides reliable results in the quantification of total,
      visceral, subcutaneous, brown and intrahepatic fat in mice. This non-invasive
      method allows the conduction of longitudinal studies of obesity in mice and
      therefore enables experimenters to investigate the onset of complex diseases such
      as diabetes and obesity.

PMID- 22615882
TI  - Circulating mesenchymal stem cells microparticles in patients with
      cerebrovascular disease.
AB  - Preclinical and clinical studies have shown that the application of CD105(+)
      mesenchymal stem cells (MSCs) is feasible and may lead to recovery after stroke.
      In addition, circulating microparticles are reportedly functional in various
      disease conditions. We tested the levels of circulating CD105(+) microparticles
      in patients with acute ischemic stroke. The expression of CD105 (a surface marker
      of MSCs) and CXCR4 (a CXC chemokine receptor for MSC homing) on circulating
      microparticles was evaluated by flow cytometry of samples from 111 patients and
      50 healthy subjects. The percentage of apoptotic CD105 microparticles was
      determined based on annexin V (AV) expression. The relationship between serum
      levels of CD105(+)/AV(-) microparticles, stromal cells derived factor-1alpha (SDF
      1alpha), and the extensiveness of cerebral infarcts was also evaluated.
      CD105(+)/AV(-) microparticles were higher in stroke patients than control
      subjects. Correlation analysis showed that the levels of CD105(+)/AV(-)
      microparticles increased as the baseline stroke severity increased. Multivariate
      testing showed that the initial severity of stroke was independently associated
      with circulating CD105(+)/AV(-) microparticles (OR, 1.103 for 1 point increase in
      the NIHSS score on admission; 95% CI, 1.032-1.178) after adjusting for other
      variables. The levels of CD105(+)/CXCR4(+)/AV(-) microparticles were also
      increased in patients with severe disability (r = 0.192, p = 0.046 for NIHSS
      score on admission), but were decreased with time after stroke onset (r = -0.204,
      p = 0.036). Risk factor profiles were not associated with the levels of
      circulating microparticles or SDF-1alpha. In conclusion, our data showed that
      stroke triggers the mobilization of MSC-derived microparticles, especially in
      patients with extensive ischemic stroke.

PMID- 22615881
TI  - Comparative proteomic analysis of Aedes aegypti larval midgut after intoxication
      with Cry11Aa toxin from Bacillus thuringiensis.
AB  - Cry toxins produced by Bacillus thuringiensis bacteria are environmentally safe
      alternatives to control insect pests. They are pore-forming toxins that
      specifically affect cell permeability and cellular integrity of insect-midgut
      cells. In this work we analyzed the defensive response of Aedes aegypti larva to
      Cry11Aa toxin intoxication by proteomic and functional genomic analyses. Two
      dimensional differential in-gel electrophoresis (2D-DIGE) was utilized to analyze
      proteomic differences among A. aegypti larvae intoxicated with different doses of
      Cry11Aa toxin compared to a buffer treatment. Spots with significant differential
      expression (p<0.05) were then identified by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS), revealing 18 up-regulated and seven down-regulated
      proteins. The most abundant subcategories of differentially expressed proteins
      were proteins involved in protein turnover and folding, energy production, and
      cytoskeleton maintenance. We selected three candidate proteins based on their
      differential expression as representatives of the different functional categories
      to perform gene silencing by RNA interference and analyze their functional role.
      The heat shock protein HSP90 was selected from the proteins involved in protein
      turnover and chaperones; actin, was selected as representative of the
      cytoskeleton protein group, and ATP synthase subunit beta was selected from the
      group of proteins involved in energy production. When we affected the expression
      of ATP synthase subunit beta and actin by silencing with RNAi the larvae became
      hypersensitive to toxin action. In addition, we found that mosquito larvae
      displayed a resistant phenotype when the heat shock protein was silenced. These
      results provide insight into the molecular components influencing the defense to
      Cry toxin intoxication and facilitate further studies on the roles of identified
      genes.

PMID- 22615883
TI  - GABA-A channel subunit expression in human glioma correlates with tumor histology
      and clinical outcome.
AB  - GABA (gamma-aminobutyric acid) is the main inhibitory neurotransmitter in the CNS
      and is present in high concentrations in presynaptic terminals of neuronal cells.
      More recently, GABA has been ascribed a more widespread role in the control of
      cell proliferation during development where low concentrations of extrasynaptic
      GABA induce a tonic activation of GABA receptors. The GABA-A receptor consists of
      a ligand-gated chloride channel, formed by five subunits that are selected from
      19 different subunit isoforms. The functional and pharmacological properties of
      the GABA-A channels are dictated by their subunit composition. Here we used qRT
      PCR to compare mRNA levels of all 19 GABA-A channel subunits in samples of human
      glioma (n = 29) and peri-tumoral tissue (n = 5). All subunits except the rho1 and
      rho3 subunit were consistently detected. Lowest mRNA levels were found in
      glioblastoma compared to gliomas of lower malignancy, except for the theta
      subunit. The expression and cellular distribution of the alpha1, gamma1, rho2 and
      theta subunit proteins was investigated by immunohistochemistry on tissue
      microarrays containing 87 gliomas grade II. We found a strong co-expression of
      rho2 and theta subunits in both astrocytomas (r = 0.86, p<0.0001) and
      oligodendroglial tumors (r = 0.66, p<0.0001). Kaplan-Meier analysis and Cox
      proportional hazards modeling to estimate the impact of GABA-A channel subunit
      expression on survival identified the rho2 subunit (p = 0.043) but not the theta
      subunit (p = 0.64) as an independent predictor of improved survival in
      astrocytomas, together with established prognostic factors. Our data give support
      for the presence of distinct GABA-A channel subtypes in gliomas and provide the
      first link between specific composition of the A-channel and patient survival.

PMID- 22615884
TI  - Residential proximity to a major roadway is associated with features of asthma
      control in children.
AB  - BACKGROUND: While several studies suggest that traffic-related air pollutants are
      detrimental for respiratory health, few studies have examined relationships
      between residential proximity to a major roadway and asthma control in children.
      Furthermore, a major limitation of existing research is reliance on self-reported
      outcomes. We therefore determined the spatial relationship between the distance
      from a major roadway and clinical, physiologic and inflammatory features of
      asthma in a highly characterized sample of asthmatic children 6-17 years of age
      across a wide range of severities. We hypothesized that a closer residential
      proximity to a major roadway would be associated with increased respiratory
      symptoms, altered pulmonary function and a greater magnitude of airway and
      systemic inflammation. METHODOLOGY/PRINCIPAL FINDINGS: 224 children 6-17 years
      with confirmed asthma completed questionnaires and underwent spirometry,
      plethysmography, exhaled nitric oxide determination, exhaled breath condensate
      collection and venipuncture. Residential distance from a major roadway was
      determined by mapping the geographic coordinates of the residential address in
      Geographic Information System software. The distance between the home address and
      the nearest major roadway was calculated according to the shortest distance
      between the two points (i.e., "as the crow flies"). Asthmatic children living in
      closer proximity to a major roadway had an increased frequency of wheezing
      associated with increased medication requirements and more hospitalizations even
      after controlling for potential confounders. These children also had increased
      airway resistance, increased airway inflammation reflected by a lower breath
      condensate pH, and higher plasma EGF concentrations. CONCLUSIONS/SIGNIFICANCE:
      These findings suggest that closer residential proximity to a major roadway is
      associated with poorer asthma control in school-age children. Assessment of
      residential proximity to major roadways may be useful in the clinical evaluation
      of asthma in children.

PMID- 22615885
TI  - A novel function of Noc2 in agonist-induced intracellular Ca2+ increase during
      zymogen-granule exocytosis in pancreatic acinar cells.
AB  - Noc2, a putative Rab effector, contributes to secretory-granule exocytosis in
      neuroendocrine and exocrine cells. Here, using two-photon excitation live-cell
      imaging, we investigated its role in Ca(2+)-dependent zymogen granule (ZG)
      exocytosis in pancreatic acinar cells from wild-type (WT) and Noc2-knockout (KO)
      mice. Imaging of a KO acinar cell revealed an expanded granular area, indicating
      ZG accumulation. In our spatiotemporal analysis of the ZG exocytosis induced by
      agonist (cholecystokinin or acetylcholine) stimulation, the location and rate of
      progress of ZG exocytosis did not differ significantly between the two strains.
      ZG exocytosis from KO acinar cells was seldom observed at physiological
      concentrations of agonists, but was normal (vs. WT) at high concentrations. Flash
      photolysis of a caged calcium compound confirmed the integrity of the fusion step
      of ZG exocytosis in KO acinar cells. The decreased ZG exocytosis present at
      physiological concentrations of agonists raised the possibility of impaired
      elicitation of calcium spikes. When calcium spikes were evoked in KO acinar cells
      by a high agonist concentration: (a) they always started at the apical portion
      and traveled to the basal portion, and (b) calcium oscillations over the 10 uM
      level were observed, as in WT acinar cells. At physiological concentrations of
      agonists, however, sufficient calcium spikes were not observed, suggesting an
      impaired [Ca(2+)](i)-increase mechanism in KO acinar cells. We propose that in
      pancreatic acinar cells, Noc2 is not indispensable for the membrane fusion of ZG
      per se, but instead performs a novel function favoring agonist-induced
      physiological [Ca(2+)](i) increases.

PMID- 22615887
TI  - Identification of milk component in ancient food residue by proteomics.
AB  - BACKGROUND: Proteomic approaches based on mass spectrometry have been recently
      used in archaeological and art researches, generating promising results for
      protein identification. Little information is known about eastward spread and
      eastern limits of prehistoric milking in eastern Eurasia. METHODOLOGY/PRINCIPAL
      FINDING: In this paper, an ancient visible food remain from Subeixi Cemeteries
      (cal. 500 to 300 years BC) of the Turpan Basin in Xinjiang, China, preliminarily
      determined containing 0.432 mg/kg cattle casein with ELISA, was analyzed by using
      an improved method based on liquid chromatography (LC) coupled with MALDI-TOF/TOF
      MS to further identify protein origin. The specific sequence of bovine casein and
      the homology sequence of goat/sheep casein were identified.
      CONCLUSIONS/SIGNIFICANCE: The existence of milk component in ancient food implies
      goat/sheep and cattle milking in ancient Subeixi region, the furthest eastern
      location of prehistoric milking in the Old World up to date. It is envisioned
      that this work provides a new approach for ancient residue analysis and other
      archaeometry field.

PMID- 22615886
TI  - Revisiting brain atrophy and its relationship to disability in multiple
      sclerosis.
AB  - BACKGROUND: Brain atrophy is a well-accepted imaging biomarker of multiple
      sclerosis (MS) that partially correlates with both physical disability and
      cognitive impairment. METHODOLOGY/PRINCIPAL FINDINGS: Based on MRI scans of 60 MS
      cases and 37 healthy volunteers, we measured the volumes of white matter (WM)
      lesions, cortical gray matter (GM), cerebral WM, caudate nucleus, putamen,
      thalamus, ventricles, and brainstem using a validated and completely automated
      segmentation method. We correlated these volumes with the Expanded Disability
      Status Scale (EDSS), MS Severity Scale (MSSS), MS Functional Composite (MSFC),
      and quantitative measures of ankle strength and toe sensation. Normalized volumes
      of both cortical and subcortical GM structures were abnormally low in the MS
      group, whereas no abnormality was found in the volume of the cerebral WM. High
      physical disability was associated with low cerebral WM, thalamus, and brainstem
      volumes (partial correlation coefficients ~0.3-0.4) but not with low cortical GM
      volume. Thalamus volumes were inversely correlated with lesion load (r = -0.36,
      p<0.005). CONCLUSION: The GM is atrophic in MS. Although lower WM volume is
      associated with greater disability, as might be expected, WM volume was on
      average in the normal range. This paradoxical result might be explained by the
      presence of coexisting pathological processes, such as tissue damage and repair,
      that cause both atrophy and hypertrophy and that underlie the observed
      disability.

PMID- 22615889
TI  - Modulation of corticospinal excitability during acquisition of action sequences
      by observation.
AB  - Excitability of the corticospinal pathway increases during observation of an
      action. However, how corticospinal excitability changes during observation of
      sequential actions in the course of acquiring novel skills (observational
      learning) remains unexplored. To investigate this, we used a previously
      unpracticed sequence of ten hand postures. Participants were asked to repeat
      observation and replication of the sequence. This block of observation and
      replication was repeated 5 times. During observation of a given hand posture (OK
      sign), motor-evoked potentials (MEPs) elicited by transcranial magnetic
      stimulation were recorded from hand muscles. In experiment 1, the OK sign
      appeared in the 9th position of the sequence. Almost all participants could
      replicate the OK sign only at the 5th block of the experiment. MEP amplitude was
      greater than that in the control, and decreased with the stages. This suggested
      that during observational learning of sequential hand postures MEP changed with
      the progress of the learning. To evaluate this idea, we performed two additional
      experiments. In experiment 2, the OK sign appeared in the 2nd position. Almost
      all participants replicated the OK sign even in the 1st block. The MEP amplitude
      did not change across stages. In experiment 3, the OK sign appeared in the 9th
      position, but the order of other signs was randomized in every stage. Many
      participants were not able to replicate the OK sign even during the 5th block of
      the experiment. The MEP amplitude did not change across stages. These results
      suggest that: (1) During observational learning modulation of corticospinal
      excitability is associated with the learning process. (2) Corticospinal
      excitability decreases as learning progresses.

PMID- 22615888
TI  - Differential contribution of hypothalamic MAPK activity to anxiety-like behaviour
      in virgin and lactating rats.
AB  - The c-Raf - MEK1/2 - ERK1/2 mitogen-activated protein kinase (MAPK) intracellular
      signalling cascade in neurons plays important roles in the control of a variety
      of behaviours, including social behaviours and anxiety. These roles partially
      overlap with those described for oxytocin (OXT), and it has been shown that OXT
      activates the MAPK pathway in the hypothalamus (of male), and hippocampus (of
      female) rats. Here, by combining behavioural (light/dark box) and biochemical
      analyses (western blotting), we tested two hypotheses: (i) that OXT is anxiolytic
      within the hypothalamus of females, and (ii) that this effect, as well as that of
      lactation-associated anxiolysis, depends on the recruitment of the MAPK pathway.
      We found that, when injected bilaterally into the hypothalamic paraventricular
      nucleus (PVN), OXT decreased anxiety-like behaviour in virgins, and that this
      effect depended on phosphorylation of MEK1/2. MAPK pathway activation in
      lactation was evident by high phosphorylated (p) MEK1/2 levels, and nuclear
      translocation of ERK1. The high pMEK1/2 levels were necessary for the anxiolytic
      phenotype typically observed during lactation. Interestingly, exogenous OXT in
      lactating rats reduced pMEK1/2 levels without a concomitant effect on anxiety,
      indicating that OXT receptor activation can lead to recruitment of additional
      intracellular pathways to modulate MEK activity. Still other pathways could
      include MEK, but without subsequent activation of ERK, as we did not observe any
      increase in OXT-induced ERK phosphorylation. Together the results demonstrate
      that the MAPK pathway, especially MEK1/2, is critically involved in the
      regulation of anxiety-like behaviour in female rats.

PMID- 22615890
TI  - Evaluation of accelerometer-based fall detection algorithms on real-world falls.
AB  - Despite extensive preventive efforts, falls continue to be a major source of
      morbidity and mortality among elderly. Real-time detection of falls and their
      urgent communication to a telecare center may enable rapid medical assistance,
      thus increasing the sense of security of the elderly and reducing some of the
      negative consequences of falls. Many different approaches have been explored to
      automatically detect a fall using inertial sensors. Although previously published
      algorithms report high sensitivity (SE) and high specificity (SP), they have
      usually been tested on simulated falls performed by healthy volunteers. We
      recently collected acceleration data during a number of real-world falls among a
      patient population with a high-fall-risk as part of the SensAction-AAL European
      project. The aim of the present study is to benchmark the performance of thirteen
      published fall-detection algorithms when they are applied to the database of 29
      real-world falls. To the best of our knowledge, this is the first systematic
      comparison of fall detection algorithms tested on real-world falls. We found that
      the SP average of the thirteen algorithms, was (mean +/- std) 83.0% +/- 30.3%
      (maximum value = 98%). The SE was considerably lower (SE = 57.0% +/- 27.3%,
      maximum value = 82.8%), much lower than the values obtained on simulated falls.
      The number of false alarms generated by the algorithms during 1-day monitoring of
      three representative fallers ranged from 3 to 85. The factors that affect the
      performance of the published algorithms, when they are applied to the real-world
      falls, are also discussed. These findings indicate the importance of testing fall
      detection algorithms in real-life conditions in order to produce more effective
      automated alarm systems with higher acceptance. Further, the present results
      support the idea that a large, shared real-world fall database could,
      potentially, provide an enhanced understanding of the fall process and the
      information needed to design and evaluate a high-performance fall detector.

PMID- 22615891
TI  - Tetraploid wheat landraces in the Mediterranean basin: taxonomy, evolution and
      genetic diversity.
AB  - The geographic distribution of genetic diversity and the population structure of
      tetraploid wheat landraces in the Mediterranean basin has received relatively
      little attention. This is complicated by the lack of consensus concerning the
      taxonomy of tetraploid wheats and by unresolved questions regarding the
      domestication and spread of naked wheats. These knowledge gaps hinder crop
      diversity conservation efforts and plant breeding programmes. We investigated
      genetic diversity and population structure in tetraploid wheats (wild emmer,
      emmer, rivet and durum) using nuclear and chloroplast simple sequence repeats,
      functional variations and insertion site-based polymorphisms. Emmer and wild
      emmer constitute a genetically distinct population from durum and rivet, the
      latter seeming to share a common gene pool. Our population structure and genetic
      diversity data suggest a dynamic history of introduction and extinction of
      genotypes in the Mediterranean fields.

PMID- 22615892
TI  - Proposed role for COUP-TFII in regulating fetal Leydig cell steroidogenesis,
      perturbation of which leads to masculinization disorders in rodents.
AB  - Reproductive disorders that are common/increasing in prevalence in human males
      may arise because of deficient androgen production/action during a fetal
      'masculinization programming window'. We identify a potentially important role
      for Chicken Ovalbumin Upstream Promoter-Transcription Factor II (COUP-TFII) in
      Leydig cell (LC) steroidogenesis that may partly explain this. In rats, fetal LC
      size and intratesticular testosterone (ITT) increased ~3-fold between e15.5-e21.5
      which associated with a progressive decrease in the percentage of LC expressing
      COUP-TFII. Exposure of fetuses to dibutyl phthalate (DBP), which induces
      masculinization disorders, dose-dependently prevented the age-related decrease in
      LC COUP-TFII expression and the normal increases in LC size and ITT. We show that
      nuclear COUP-TFII expression in fetal rat LC relates inversely to LC expression
      of steroidogenic factor-1 (SF-1)-dependent genes (StAR, Cyp11a1, Cyp17a1) with
      overlapping binding sites for SF-1 and COUP-TFII in their promoter regions, but
      does not affect an SF-1 dependent LC gene (3beta-HSD) without overlapping sites.
      We also show that once COUP-TFII expression in LC has switched off, it is re
      induced by DBP exposure, coincident with suppression of ITT. Furthermore, other
      treatments that reduce fetal ITT in rats (dexamethasone, diethylstilbestrol
      (DES)) also maintain/induce LC nuclear expression of COUP-TFII. In contrast to
      rats, in mice DBP neither causes persistence of fetal LC COUP-TFII nor reduces
      ITT, whereas DES-exposure of mice maintains COUP-TFII expression in fetal LC and
      decreases ITT, as in rats. These findings suggest that lifting of repression by
      COUP-TFII may be an important mechanism that promotes increased testosterone
      production by fetal LC to drive masculinization. As we also show an age-related
      decline in expression of COUP-TFII in human fetal LC, this mechanism may also be
      functional in humans, and its susceptibility to disruption by environmental
      chemicals, stress and pregnancy hormones could explain the origin of some human
      male reproductive disorders.

PMID- 22615893
TI  - The spread of influenza A(H1N1)pdm09 virus in Madagascar described by a sentinel
      surveillance network.
AB  - BACKGROUND: The influenza A(H1N1)pdm09 virus has been a challenge for public
      health surveillance systems in all countries. In Antananarivo, the first imported
      case was reported on August 12, 2009. This work describes the spread of
      A(H1N1)pdm09 in Madagascar. METHODS: The diffusion of influenza A(H1N1)pdm09 in
      Madagascar was explored using notification data from a sentinel network. Clinical
      data were charted to identify peaks at each sentinel site and virological data
      was used to confirm viral circulation. RESULTS: From August 1, 2009 to February
      28, 2010, 7,427 patients with influenza-like illness were reported. Most patients
      were aged 7 to 14 years. Laboratory tests confirmed infection with A(H1N1)pdm09
      in 237 (33.2%) of 750 specimens. The incidence of patients differed between
      regions. By determining the epidemic peaks we traced the diffusion of the
      epidemic through locations and time in Madagascar. The first peak was detected
      during the epidemiological week 47-2009 in Antananarivo and the last one occurred
      in week 07-2010 in Tsiroanomandidy. CONCLUSION: Sentinel surveillance data can be
      used for describing epidemic trends, facilitating the development of
      interventions at the local level to mitigate disease spread and impact.

PMID- 22615894
TI  - The impact of human conflict on the genetics of Mastomys natalensis and Lassa
      virus in West Africa.
AB  - Environmental changes have been shown to play an important role in the emergence
      of new human diseases of zoonotic origin. The contribution of social factors to
      their spread, especially conflicts followed by mass movement of populations, has
      not been extensively investigated. Here we reveal the effects of civil war on the
      phylogeography of a zoonotic emerging infectious disease by concomitantly
      studying the population structure, evolution and demography of Lassa virus and
      its natural reservoir, the rodent Mastomys natalensis, in Guinea, West Africa.
      Analysis of nucleoprotein gene sequences enabled us to reconstruct the
      evolutionary history of Lassa virus, which appeared 750 to 900 years ago in
      Nigeria and only recently spread across western Africa (170 years ago). Bayesian
      demographic inferences revealed that both the host and the virus populations have
      gone recently through severe genetic bottlenecks. The timing of these events
      matches civil war-related mass movements of refugees and accompanying
      environmental degradation. Forest and habitat destruction and human predation of
      the natural reservoir are likely explanations for the sharp decline observed in
      the rodent populations, the consequent virus population decline, and the
      coincident increased incidence of Lassa fever in these regions. Interestingly, we
      were also able to detect a similar pattern in Nigeria coinciding with the Biafra
      war. Our findings show that anthropogenic factors may profoundly impact the
      population genetics of a virus and its reservoir within the context of an
      emerging infectious disease.

PMID- 22615896
TI  - Multiple fitness benefits of polyandry in a cephalopod.
AB  - BACKGROUND: Sex differences in reproductive investment play a crucial role in
      sexual conflict. One intriguing aspect of sexual conflict is the evolution of
      female multiple mating (polyandry), particularly in systems where females receive
      no obvious direct benefits from males, and where mating is highly costly. Here,
      theory predicts that polyandrous females can increase their reproductive success
      by taking advantage of the genetic benefits of mating with multiple males.
      Cephalopods provide a model system for addressing this question, as all species
      mate multiply. Here we examine differences in reproductive success between
      monandrous, multiply mated (to the same male) and polyandrous female dumpling
      squid (Euprymna tasmanica). METHODOLOGY/PRINCIPAL FINDINGS: We mated females in
      the laboratory with two different males (polyandrous; controlling for mating
      order), or with a single male (monandrous). To control for mating frequency, we
      mated monandrous females either once (monandrous 1), or with the same male twice
      (monandrous 2), and measured reproductive success for each of the three
      treatments (polyandrous, monandrous 1, monandrous 2). Females mated to two
      different males produced eggs faster and had larger hatchlings relative to egg
      mass than females mated once with a single male. CONCLUSIONS/SIGNIFICANCE: The
      benefits of polyandry demonstrated here are the first, to our knowledge, in any
      cephalopod. These benefits may outweigh the significant costs associated with
      mating and help to explain how multiple mating has evolved (or is maintained) in
      this group.

PMID- 22615895
TI  - Targeting of the human coagulation factor IX gene at rDNA locus of human
      embryonic stem cells.
AB  - BACKGROUND: Genetic modification is a prerequisite to realizing the full
      potential of human embryonic stem cells (hESCs) in human genetic research and
      regenerative medicine. Unfortunately, the random integration methods that have
      been the primary techniques used keep creating problems, and the primary
      alternative method, gene targeting, has been effective in manipulating mouse
      embryonic stem cells (mESCs) but poorly in hESCs. METHODOLOGY/PRINCIPAL FINDINGS:
      Human ribosomal DNA (rDNA) repeats are clustered on the short arm of acrocentric
      chromosomes. They consist of approximately 400 copies of the 45S pre-RNA (rRNA)
      gene per haploid. In the present study, we targeted a physiological gene, human
      coagulation factor IX, into the rDNA locus of hESCs via homologous recombination.
      The relative gene targeting efficiency (>50%) and homologous recombination
      frequency (>10(-5)) were more than 10-fold higher than those of loci targeted in
      previous reports. Meanwhile, the targeted clones retained both a normal karyotype
      and the main characteristics of ES cells. The transgene was found to be stably
      and ectopically expressed in targeted hESCs. CONCLUSION/SIGNIFICANCE: This is the
      first targeting of a human physiological gene at a defined locus on the hESC
      genome. Our findings indicate that the rDNA locus may serve as an ideal harbor
      for transgenes in hESCs.

PMID- 22615897
TI  - Increased expression of PITX2 transcription factor contributes to ovarian cancer
      progression.
AB  - BACKGROUND: Paired-like homeodomain 2 (PITX2) is a bicoid homeodomain
      transcription factor which plays an essential role in maintaining embryonic left
      right asymmetry during vertebrate embryogenesis. However, emerging evidence
      suggests that the aberrant upregulation of PITX2 may be associated with tumor
      progression, yet the functional role that PITX2 plays in tumorigenesis remains
      unknown. PRINCIPAL FINDINGS: Using real-time quantitative RT-PCR (Q-PCR), Western
      blot and immunohistochemical (IHC) analyses, we demonstrated that PITX2 was
      frequently overexpressed in ovarian cancer samples and cell lines.
      Clinicopathological correlation showed that the upregulated PITX2 was
      significantly associated with high-grade (P = 0.023) and clear cell subtype (P =
      0.011) using Q-PCR and high-grade (P<0.001) ovarian cancer by IHC analysis.
      Functionally, enforced expression of PITX2 could promote ovarian cancer cell
      proliferation, anchorage-independent growth ability, migration/invasion and tumor
      growth in xenograft model mice. Moreover, enforced expression of PITX2 elevated
      the cell cycle regulatory proteins such as Cyclin-D1 and C-myc. Conversely, RNAi
      mediated knockdown of PITX2 in PITX2-high expressing ovarian cancer cells had the
      opposite effect. CONCLUSION: Our findings suggest that the increased expression
      PITX2 is involved in ovarian cancer progression through promoting cell growth and
      cell migration/invasion. Thus, targeting PITX2 may serve as a potential
      therapeutic modality in the management of high-grade ovarian tumor.

PMID- 22615898
TI  - Genetic structure and inferences on potential source areas for Bactrocera
      dorsalis (Hendel) based on mitochondrial and microsatellite markers.
AB  - Bactrocera dorsalis (Diptera: Tephritidae) is mainly distributed in tropical and
      subtropical Asia and in the Pacific region. Despite its economic importance, very
      few studies have addressed the question of the wide genetic structure and
      potential source area of this species. This pilot study attempts to infer the
      native region of this pest and its colonization pathways in Asia. Combining
      mitochondrial and microsatellite markers, we evaluated the level of genetic
      diversity, genetic structure, and the gene flow among fly populations collected
      across Southeast Asia and China. A complex and significant genetic structure
      corresponding to the geographic pattern was found with both types of molecular
      markers. However, the genetic structure found was rather weak in both cases, and
      no pattern of isolation by distance was identified. Multiple long-distance
      dispersal events and miscellaneous host selection by this species may explain the
      results. These complex patterns may have been influenced by human-mediated
      transportation of the pest from one area to another and the complex topography of
      the study region. For both mitochondrial and microsatellite data, no signs of
      bottleneck or founder events could be identified. Nonetheless, maximal genetic
      diversity was observed in Myanmar, Vietnam and Guangdong (China) and asymmetric
      migration patterns were found. These results provide indirect evidence that the
      tropical regions of Southeast Asia and southern coast of China may be considered
      as the native range of the species and the population expansion is northward.
      Yunnan (China) is a contact zone that has been colonized from different sources.
      Regions along the southern coast of Vietnam and China probably served to colonize
      mainly the southern region of China. Southern coastal regions of China may also
      have colonized central parts of China and of central Yunnan.

PMID- 22615899
TI  - Calpain activity is essential in skin wound healing and contributes to scar
      formation.
AB  - Wound healing is a multistep phenomenon that relies on complex interactions
      between various cell types. Calpains are ubiquitously expressed proteases
      regulating several processes including cellular adhesion and motility as well as
      inflammation and angiogenesis. Calpains can be targeted by inhibitors, and their
      inhibition was shown to reduce organ damage in various disease models. We aimed
      to assess the role of calpains in skin healing and the potential benefit of
      calpain inhibition on scar formation. We used a pertinent model where calpain
      activity is inhibited only in lesional organs, namely transgenic mice
      overexpressing calpastatin (CPST), a specific natural calpain inhibitor. CPST
      mice showed a striking delay in wound healing particularly in the initial steps
      compared to wild types (WT). CPST wounds displayed reduced proliferation in the
      epidermis and delayed re-epithelization. Granulation tissue formation was
      impaired in CPST mice, with a reduction in CD45+ leukocyte infiltrate and in
      CD31+ blood vessel density. Interestingly, wounds on WT skin grafted on CPST mice
      (WT/CPST) showed a similar delayed healing with reduced angiogenesis and
      inflammation compared to wounds on WT/WT mice demonstrating the implication of
      calpain activity in distant extra-cutaneous cells during wound healing. CPST
      wounds showed a reduction in alpha-smooth muscle actin (alphaSMA) expressing
      myofibroblasts as well as alphaSMA RNA expression suggesting a defect in
      granulation tissue contraction. At later stages of skin healing, calpain
      inhibition proved beneficial by reducing collagen production and wound fibrosis.
      In vitro, human fibroblasts exposed to calpeptin, a pan-calpain inhibitor, showed
      reduced collagen synthesis, impaired TGFbeta-induced differentiation into
      alphaSMA-expressing myofibroblasts, and were less efficient in a collagen gel
      contraction assay. In conclusion, calpains are major players in granulation
      tissue formation. In view of their specific effects on fibroblasts a late
      inhibition of calpains should be considered for scar reduction.

PMID- 22615900
TI  - Arabidopsis RPT2a, 19S proteasome subunit, regulates gene silencing via DNA
      methylation.
AB  - The ubiquitin/proteasome pathway plays a crucial role in many biological
      processes. Here we report a novel role for the Arabidopsis 19S proteasome subunit
      RPT2a in regulating gene activity at the transcriptional level via DNA
      methylation. Knockout mutation of the RPT2a gene did not alter global protein
      levels; however, the transcriptional activities of reporter transgenes were
      severely reduced compared to those in the wild type. This transcriptional gene
      silencing (TGS) was observed for transgenes under control of either the
      constitutive CaMV 35S promoter or the cold-inducible RD29A promoter. Bisulfite
      sequencing analysis revealed that both the transgene and endogenous RD29A
      promoter regions were hypermethylated at CG and non-CG contexts in the rpt2a
      mutant. Moreover, the TGS of transgenes driven by the CaMV 35S promoters was
      released by treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine,
      but not by application of the inhibitor of histone deacetylase Trichostatin A.
      Genetic crosses with the DNA methyltransferase met1 single or drm1drm2cmt3 triple
      mutants also resulted in a release of CaMV 35S transgene TGS in the rpt2a mutant
      background. Increased methylation was also found at transposon sequences,
      suggesting that the 19S proteasome containing AtRPT2a negatively regulates TGS at
      transgenes and at specific endogenous genes through DNA methylation.

PMID- 22615901
TI  - Association of typical versus atypical antipsychotics with symptoms and quality
      of life in schizophrenia.
AB  - BACKGROUND: Several reports on patients with chronic schizophrenia suggest that
      atypical versus typical antipsychotics are expected to lead to better quality of
      life (QOL) and cognitive function. Our aim was to examine the association of
      chronic treatment with typical or atypical antipsychotics with cognitive
      function, psychiatric symptoms, QOL, and drug-induced extrapyramidal symptoms in
      long-hospitalized patients with schizophrenia. METHODOLOGY AND PRINCIPAL
      FINDINGS: The Hasegawa Dementia Scale-Revised (HDS-R), Brief Psychiatric Rating
      Scale (BPRS), the Schizophrenia Quality of Life Scale, translated into Japanese
      (JSQLS), and the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) were used to
      evaluate cognitive function, psychiatric symptoms, QOL, and drug-induced
      extrapyramidal symptoms. We examined the correlation between the dose of
      antipsychotics and each measure derived from these psychometric tests. The
      student t-test was used to compare scores obtained from psychometric tests
      between patients receiving typical and atypical antipsychotics. Results showed
      significant correlations between chlorpromazine (CPZ)-equivalent doses of typical
      antipsychotics and atypical antipsychotics, and the total BPRS score and BPRS
      subscale scores for positive symptoms. CPZ-equivalent doses of typical
      antipsychotics were correlated with the JSQLS subscale score for dysfunction of
      psycho-social activity and DIEPSS score. Furthermore, the total BPRS scores, BPRS
      subscale score for positive symptoms, the JSQLS subscale score for dysfunction of
      psycho-social activity, and the DIEPSS score were significantly higher in
      patients receiving typical antipsychotics than atypical antipsychotics.
      CONCLUSION AND SIGNIFICANCE: These findings suggest that long-term administration
      of typical antipsychotics has an unfavorable association with feelings of
      difficulties mixing in social situations in patients with chronic schizophrenia.

PMID- 22615902
TI  - A comprehensive breath plume model for disease transmission via expiratory
      aerosols.
AB  - The peak in influenza incidence during wintertime in temperate regions represents
      a longstanding, unresolved scientific question. One hypothesis is that the
      efficacy of airborne transmission via aerosols is increased at lower humidities
      and temperatures, conditions that prevail in wintertime. Recent work with a
      guinea pig model by Lowen et al. indicated that humidity and temperature do
      modulate airborne influenza virus transmission, and several investigators have
      interpreted the observed humidity dependence in terms of airborne virus
      survivability. This interpretation, however, neglects two key observations: the
      effect of ambient temperature on the viral growth kinetics within the animals,
      and the strong influence of the background airflow on transmission. Here we
      provide a comprehensive theoretical framework for assessing the probability of
      disease transmission via expiratory aerosols between test animals in laboratory
      conditions. The spread of aerosols emitted from an infected animal is modeled
      using dispersion theory for a homogeneous turbulent airflow. The concentration
      and size distribution of the evaporating droplets in the resulting "Gaussian
      breath plume" are calculated as functions of position, humidity, and temperature.
      The overall transmission probability is modeled with a combination of the time
      dependent viral concentration in the infected animal and the probability of
      droplet inhalation by the exposed animal downstream. We demonstrate that the
      breath plume model is broadly consistent with the results of Lowen et al.,
      without invoking airborne virus survivability. The results also suggest that, at
      least for guinea pigs, variation in viral kinetics within the infected animals is
      the dominant factor explaining the increased transmission probability observed at
      lower temperatures.

PMID- 22615903
TI  - Ammonium is toxic for aging yeast cells, inducing death and shortening of the
      chronological lifespan.
AB  - Here we show that in aging Saccharomyces cerevisiae (budding yeast) cells, NH(4)
      (+) induces cell death associated with shortening of chronological life span.
      This effect is positively correlated with the concentration of NH(4) (+) added to
      the culture medium and is particularly evident when cells are starved for
      auxotrophy-complementing amino acids. NH(4) (+)-induced cell death is accompanied
      by an initial small increase of apoptotic cells followed by extensive necrosis.
      Autophagy is inhibited by NH(4) (+), but this does not cause a decrease in cell
      viability. We propose that the toxic effects of NH(4) (+) are mediated by
      activation of PKA and TOR and inhibition of Sch9p. Our data show that NH(4) (+)
      induces cell death in aging cultures through the regulation of evolutionary
      conserved pathways. They may also provide new insights into longevity regulation
      in multicellular organisms and increase our understanding of human disorders such
      as hyperammonemia as well as effects of amino acid deprivation employed as a
      therapeutic strategy.

PMID- 22615904
TI  - Phenotypic and functional changes in blood monocytes following adherence to
      endothelium.
AB  - OBJECTIVE: Blood monocytes are known to express endothelial-like genes during co
      culture with endothelium. In this study, the time-dependent change in the
      phenotype pattern of primary blood monocytes after adhering to endothelium is
      reported using a novel HLA-A2 mistyped co-culture model. METHODS AND RESULTS:
      Freshly isolated human PBMCs were co-cultured with human umbilical vein
      endothelial cells or human coronary arterial endothelial cells of converse human
      leukocyte antigen A2 (HLA-A2) status. This allows the tracking of the PBMC
      derived cells by HLA-A2 expression and assessment of their phenotype pattern over
      time. PBMCs that adhered to the endothelium at the start of the co-culture were
      predominantly CD11b+ blood monocytes. After 24 to 72 hours in co-culture, the
      endothelium-adherent monocytes acquired endothelial-like properties including the
      expression of endothelial nitric oxide synthase, CD105, CD144 and vascular
      endothelial growth factor receptor 2. The expression of monocyte/macrophage
      lineage antigens CD14, CD11b and CD36 were down regulated concomitantly. The
      adherent monocytes did not express CD115 after 1 day of co-culture. By day 6, the
      monocyte-derived cells expressed vascular cell adhesion molecule 1 in response to
      tumour necrosis factor alpha. Up to 10% of the PBMCs adhered to the endothelium.
      These monocyte-derived cells contributed up to 30% of the co-cultured cell layer
      and this was dose-dependent on the PBMC seeding density. CONCLUSIONS: Human blood
      monocytes undergo rapid phenotype change to resemble endothelial cells after
      adhering to endothelium.

PMID- 22615905
TI  - Functions of protosilencers in the formation and maintenance of heterochromatin
      in Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, transcriptionally silent heterochromatin at HML and
      HMR loci is established by silencers that recruit SIR complex and promote its
      propagation along chromatin. Silencers consist of various combinations of two or
      three binding sites for origin recognition complex (ORC), Abf1 and Rap1. A single
      ORC, Abf1 or Rap1 site cannot promote silencing, but can enhance silencing by a
      distant silencer, and is called a protosilencer. The mechanism of protosilencer
      function is not known. We examine the functions of ORC, Abf1 and Rap1 sites as
      components of the HMR-E silencer, and as protosilencers. We find that the Rap1
      site makes a larger and unique contribution to HMR-E function compared to ORC and
      Abf1 sites. On the other hand, Rap1 site does not act as a protosilencer to
      assist HML-E silencer in forming heterochromatin, whereas ORC and Abf1 sites do.
      Therefore, different mechanisms may be involved in the roles of Rap1 site as a
      component of HMR-E and as a protosilencer. Heterochromatin formed by ORC or Abf1
      site in collaboration with HML-E is not as stable as that formed by HMR-E and HML
      E, but increasing the copy number of Abf1 site enhances heterochromatin
      stability. ORC and Abf1 sites acting as protosilencers do not modulate chromatin
      structure in the absence of SIR complex, which argues against the hypothesis that
      protosilencers serve to create a chromatin structure favorable for SIR complex
      propagation. We also investigate the function of ARS1 containing an ORC site and
      an Abf1 site as a protosilencer. We find that ARS1 inserted at HML enhances
      heterochromatin stability, and promotes de novo formation of a chromatin
      structure that partially resembles heterochromatin in an S phase dependent
      manner. Taken together, our results indicate that protosilencers aid in the
      formation and maintenance of heterochromatin structure.

PMID- 22615906
TI  - A dual-color luciferase assay system reveals circadian resetting of cultured
      fibroblasts by co-cultured adrenal glands.
AB  - In mammals, circadian rhythms of various organs and tissues are synchronized by
      pacemaker neurons in the suprachiasmatic nucleus (SCN) of the hypothalamus.
      Glucocorticoids released from the adrenal glands can synchronize circadian
      rhythms in other tissues. Many hormones show circadian rhythms in their plasma
      concentrations; however, whether organs outside the SCN can serve as master
      synchronizers to entrain circadian rhythms in target tissues is not well
      understood. To further delineate the function of the adrenal glands and the
      interactions of circadian rhythms in putative master synchronizing organs and
      their target tissues, here we report a simple co-culture system using a dual
      color luciferase assay to monitor circadian rhythms separately in various
      explanted tissues and fibroblasts. In this system, circadian rhythms of organs
      and target cells were simultaneously tracked by the green-emitting beetle
      luciferase from Pyrearinus termitilluminans (ELuc) and the red-emitting beetle
      luciferase from Phrixothrix hirtus (SLR), respectively. We obtained tissues from
      the adrenal glands, thyroid glands, and lungs of transgenic mice that expressed
      ELuc under control of the promoter from a canonical clock gene, mBmal1. The
      tissues were co-cultured with Rat-1 fibroblasts as representative target cells
      expressing SLR under control of the mBmal1 promoter. Amplitudes of the circadian
      rhythms of Rat-1 fibroblasts were potentiated when the fibroblasts were co
      cultured with adrenal gland tissue, but not when co-cultured with thyroid gland
      or lung tissue. The phases of Rat-1 fibroblasts were reset by application of
      adrenal gland tissue, whereas the phases of adrenal gland tissue were not
      influenced by Rat-1 fibroblasts. Furthermore, the effect of the adrenal gland
      tissue on the fibroblasts was blocked by application of a glucocorticoid receptor
      (GR) antagonist. These results demonstrate that glucocorticoids are strong
      circadian synchronizers for fibroblasts and that this co-culture system is a
      useful tool to analyze humoral communication between different tissues or cell
      populations.

PMID- 22615907
TI  - Concurrent word generation and motor performance: further evidence for language
      motor interaction.
AB  - Embodied/modality-specific theories of semantic memory propose that sensorimotor
      representations play an important role in perception and action. A large body of
      evidence supports the notion that concepts involving human motor action (i.e.,
      semantic-motor representations) are processed in both language and motor regions
      of the brain. However, most studies have focused on perceptual tasks, leaving
      unanswered questions about language-motor interaction during production tasks.
      Thus, we investigated the effects of shared semantic-motor representations on
      concurrent language and motor production tasks in healthy young adults,
      manipulating the semantic task (motor-related vs. nonmotor-related words) and the
      motor task (i.e., standing still and finger-tapping). In Experiment 1 (n = 20),
      we demonstrated that motor-related word generation was sufficient to affect
      postural control. In Experiment 2 (n = 40), we demonstrated that motor-related
      word generation was sufficient to facilitate word generation and finger tapping.
      We conclude that engaging semantic-motor representations can have a reciprocal
      influence on motor and language production. Our study provides additional support
      for functional language-motor interaction, as well as embodied/modality-specific
      theories.

PMID- 22615908
TI  - Down-regulation of AP-4 inhibits proliferation, induces cell cycle arrest and
      promotes apoptosis in human gastric cancer cells.
AB  - BACKGROUND: AP-4 belongs to the basic helix-loop-helix leucine-zipper subgroup;
      it controls target gene expression, regulates growth, development and cell
      apoptosis and has been implicated in tumorigenesis. Our previous studies
      indicated that AP-4 was frequently overexpressed in gastric cancers and may be
      associated with the poor prognosis. The purpose of this study is to examine
      whether silencing of AP-4 can alter biological characteristics of gastric cancer
      cells. METHODS: Two specific siRNAs targeting AP-4 were designed, synthesized,
      and transfected into gastric cancer cell lines and human normal mucosa cells. AP
      4 expression was measured with real-time quantitative PCR and Western blot. Cell
      proliferation and chemo-sensitivity were detected by CCK-8 assay. Cell cycle
      assay and apoptosis assay were performed by flow cytometer, and relative
      expression of cell cycle regulators were detected by real-time quantitative PCR
      and Western blot, expression of the factors involved in the apoptosis pathway
      were examined in mRNA and protein level. RESULTS: The expression of AP-4 was
      silenced by the siRNAs transfection and the effects of AP-4 knockdown lasted 24
      to 96 hrs. The siRNA-mediated silencing of AP-4 suppressed the cellular
      proliferation, induced apoptosis and sensitized cancer cells to anticancer drugs.
      In addition, the expression level of p21, p53 and Caspase-9 were increased when
      AP-4 was knockdown, but the expression of cyclin D1, Bcl-2 and Bcl-x(L) was
      inhibited. It didn't induce cell cycle arrest when AP-4 was knockdown in p53
      defect gastric cancer cell line Kato-III. CONCLUSIONS: These results illustrated
      that gene silencing of AP-4 can efficiently inhibited cell proliferation,
      triggered apoptosis and sensitized cancer cells to anticancer drugs in vitro,
      suggesting that AP-4 siRNAs mediated silencing has a potential value in the
      treatment of human gastric cancer.

PMID- 22615909
TI  - Examining the interactome of huperzine A by magnetic biopanning.
AB  - Huperzine A is a bioactive compound derived from traditional Chinese medicine
      plant Qian Ceng Ta (Huperzia serrata), and was found to have multiple
      neuroprotective effects. In addition to being a potent acetylcholinesterase
      inhibitor, it was thought to act through other mechanisms such as antioxidation,
      antiapoptosis, etc. However, the molecular targets involved with these mechanisms
      were not identified. In this study, we attempted to exam the interactome of
      Huperzine A using a cDNA phage display library and also mammalian brain tissue
      extracts. The drugs were chemically linked on the surface of magnetic particles
      and the interactive phages or proteins were collected and analyzed. Among the
      various cDNA expressing phages selected, one was identified to encode the
      mitochondria NADH dehydrogenase subunit 1. Specific bindings between the drug and
      the target phages and target proteins were confirmed. Another enriched phage
      clone was identified as mitochondria ATP synthase, which was also panned out from
      the proteome of mouse brain tissue lysate. These data indicated the possible
      involvement of mitochondrial respiratory chain matrix enzymes in Huperzine A's
      pharmacological effects. Such involvement had been suggested by previous studies
      based on enzyme activity changes. Our data supported the new mechanism. Overall
      we demonstrated the feasibility of using magnetic biopanning as a simple and
      viable method for investigating the complex molecular mechanisms of bioactive
      molecules.

PMID- 22615910
TI  - Evidence for the 'good genes' model: association of MHC class II DRB alleles with
      ectoparasitism and reproductive state in the neotropical lesser bulldog bat,
      Noctilio albiventris.
AB  - The adaptive immune system has a major impact on parasite resistance and life
      history strategies. Immunological defence is costly both in terms of immediate
      activation and long-term maintenance. The 'good genes' model predicts that males
      with genotypes that promote a good disease resistance have the ability to
      allocate more resources to reproductive effort which favours the transmission of
      good alleles into future generations. Our study shows a correlation between
      immune gene constitution (Major Histocompatibility Complex, MHC class II DRB),
      ectoparasite loads (ticks and bat flies) and the reproductive state in a
      neotropical bat, Noctilio albiventris. Infestation rates with ectoparasites were
      linked to specific Noal-DRB alleles, differed among roosts, increased with body
      size and co-varied with reproductive state particularly in males. Non
      reproductive adult males were more infested with ectoparasites than
      reproductively active males, and they had more often an allele (Noal-DRB*02)
      associated with a higher tick infestation than reproductively active males or
      subadults. We conclude that the individual immune gene constitution affects
      ectoparasite susceptibility, and contributes to fitness relevant trade-offs in
      male N. albiventris as suggested by the 'good genes' model.

PMID- 22615912
TI  - Fetal and early post-natal mineralization of the tympanic bulla in fin whales may
      reveal a Hitherto undiscovered evolutionary trait.
AB  - The evolution of the cetacean skeleton followed a path that differentiated this
      group from other terrestrial mammals about 50 million years ago [1], and debate
      is still going on about the relationships between Cetacea and Artiodactyla [2],
      [3], [4]. Some skeletal traits of the basilosaurids (the more advanced forms of
      Archaeocetes), such as the expansion of the peribullary air sinuses, dental
      modification and vertebral size uniformity [5] are maintained and further
      emphasized also in contemporary odontocetes and mysticetes. Using Dual-Energy X
      Ray Absorptiometry here we report that the deposition of bone mineral in fetal
      and newborn specimens of the fin whale Balaenoptera physalus is remarkably higher
      in the bulla tympanica than in the adjacent basal skull or in the rest of the
      skeleton. Ossification of the tympanic bulla in fetal Artiodactyla (bovine,
      hippopotamus) is minimal, becomes sensible after birth and then progresses during
      growth, contrarily to the precocious mineralization that we observed in fin
      whales. Given the importance of the ear bones for the precise identification of
      phylogenetic relationship in therian evolution [6], this feature may indicate a
      specific evolutionary trait of fin whales and possibly other cetacean species or
      families. Early mineralization of the tympanic bulla allows immediate sound
      conduction in the aquatic medium and consequently holds potential importance for
      mother-calf relationship and postnatal survival.

PMID- 22615911
TI  - PCB 126 and other dioxin-like PCBs specifically suppress hepatic PEPCK expression
      via the aryl hydrocarbon receptor.
AB  - Dioxins and dioxin-like compounds encompass a group of structurally related
      heterocyclic compounds that bind to and activate the aryl hydrocarbon receptor
      (AhR). The prototypical dioxin is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a
      highly toxic industrial byproduct that incites numerous adverse physiological
      effects. Global commercial production of the structurally similar polychlorinated
      biphenyls (PCBs), however, commenced early in the 20(th) century and continued
      for decades; dioxin-like PCBs therefore contribute significantly to total dioxin
      associated toxicity. In this study, PCB 126, the most potent dioxin-like PCB, was
      evaluated with respect to its direct effects on hepatic glucose metabolism using
      primary mouse hepatocytes. Overnight treatment with PCB 126 reduced hepatic
      glycogen stores in a dose-dependent manner. Additionally, PCB 126 suppressed
      forskolin-stimulated gluconeogenesis from lactate. These effects were independent
      of acute toxicity, as PCB 126 did not increase lactate dehydrogenase release nor
      affect lipid metabolism or total intracellular ATP. Interestingly, provision of
      cells with glycerol instead of lactate as the carbon source completely restored
      hepatic glucose production, indicating specific impairment in the distal arm of
      gluconeogenesis. In concordance with this finding, PCB 126 blunted the forskolin
      stimulated increase in phosphoenolpyruvate carboxykinase (PEPCK) mRNA levels
      without affecting glucose-6-phosphatase expression. Myricetin, a putative
      competitive AhR antagonist, reversed the suppression of PEPCK induction by PCB
      126. Furthermore, other dioxin-like PCBs demonstrated similar effects on PEPCK
      expression in parallel with their ability to activate AhR. It therefore appears
      that AhR activation mediates the suppression of PEPCK expression by dioxin-like
      PCBs, suggesting a role for these pollutants as disruptors of energy metabolism.

PMID- 22615913
TI  - Seroprevalence of IgG antibodies against Echinococcus granulosus in the
      population of the region of Thessaly, Central Greece.
AB  - Echinococcosis notification rate in Greece, based on the most recent data, is
      below 0.25 per 100,000 population. To further investigate the epidemiology of
      echinococcosis in Greece a study was designed to determine the seroprevalence of
      Echinococcus granulosus antibodies in the population of Thessaly, Central Greece.
      Five hundred and forty two left over blood samples in Thessaly laboratories, were
      collected using a stratified convenient sampling procedure. Samples were analyzed
      with enzyme linked immunosorbent assay. The seropositivity found was 1.1%(95%
      C.I., 0.5-2.5), with 5 out of 6 seropositive results to be in the age group of
      over 65 (OR = 17.95, 95%CI 2.04-157.11, p value 0.009). Rural residence was also
      found as a risk factor to seropositivity (RR = 7.60, 95% CI 0.89-64.64, p value
      0.039). Surveillance data and our study results converge that echinococcosis is
      being reduced in Greece, with older population to be affected mostly. These might
      be due to the disease transmission restriction, by the control measures being
      implemented. Efforts should be continued, in both animals and humans side, by
      increasing training campaigns and public awareness.

PMID- 22615914
TI  - Experimental incubations elicit profound changes in community transcription in
      OMZ bacterioplankton.
AB  - Sequencing of microbial community RNA (metatranscriptome) is a useful approach
      for assessing gene expression in microorganisms from the natural environment.
      This method has revealed transcriptional patterns in situ, but can also be used
      to detect transcriptional cascades in microcosms following experimental
      perturbation. Unambiguously identifying differential transcription between
      control and experimental treatments requires constraining effects that are simply
      due to sampling and bottle enclosure. These effects remain largely
      uncharacterized for "challenging" microbial samples, such as those from anoxic
      regions that require special handling to maintain in situ conditions. Here, we
      demonstrate substantial changes in microbial transcription induced by sample
      collection and incubation in experimental bioreactors. Microbial communities were
      sampled from the water column of a marine oxygen minimum zone by a pump system
      that introduced minimal oxygen contamination and subsequently incubated in
      bioreactors under near in situ oxygen and temperature conditions. Relative to the
      source water, experimental samples became dominated by transcripts suggestive of
      cell stress, including chaperone, protease, and RNA degradation genes from
      diverse taxa, with strong representation from SAR11-like alphaproteobacteria. In
      tandem, transcripts matching facultative anaerobic gammaproteobacteria of the
      Alteromonadales (e.g., Colwellia) increased 4-13 fold up to 43% of coding
      transcripts, and encoded a diverse gene set suggestive of protein synthesis and
      cell growth. We interpret these patterns as taxon-specific responses to combined
      environmental changes in the bioreactors, including shifts in substrate or oxygen
      availability, and minor temperature and pressure changes during sampling with the
      pump system. Whether such changes confound analysis of transcriptional patterns
      may vary based on the design of the experiment, the taxonomic composition of the
      source community, and on the metabolic linkages between community members. These
      data highlight the impressive capacity for transcriptional changes within complex
      microbial communities, underscoring the need for caution when inferring in situ
      metabolism based on transcript abundances in experimental incubations.

PMID- 22615915
TI  - Crystal structure of a complex of DNA with one AT-hook of HMGA1.
AB  - We present here for the first time the crystal structure of an AT-hook domain. We
      show the structure of an AT-hook of the ubiquitous nuclear protein HMGA1,
      combined with the oligonucleotide d(CGAATTAATTCG)(2), which has two potential
      AATT interacting groups. Interaction with only one of them is found. The
      structure presents analogies and significant differences with previous NMR
      studies: the AT-hook forms hydrogen bonds between main-chain NH groups and
      thymines in the minor groove, DNA is bent and the minor groove is widened.

PMID- 22615916
TI  - Theropod fauna from southern Australia indicates high polar diversity and climate
      driven dinosaur provinciality.
AB  - The Early Cretaceous fauna of Victoria, Australia, provides unique data on the
      composition of high latitude southern hemisphere dinosaurs. We describe and
      review theropod dinosaur postcranial remains from the Aptian-Albian Otway and
      Strzelecki groups, based on at least 37 isolated bones, and more than 90 teeth
      from the Flat Rocks locality. Several specimens of medium- and large-bodied
      individuals (estimated up to ~8.5 metres long) represent allosauroids.
      Tyrannosauroids are represented by elements indicating medium body sizes (~3
      metres long), likely including the holotype femur of Timimus hermani, and a
      single cervical vertebra represents a juvenile spinosaurid. Single specimens
      representing medium- and small-bodied theropods may be referrable to
      Ceratosauria, Ornithomimosauria, a basal coelurosaur, and at least three taxa
      within Maniraptora. Thus, nine theropod taxa may have been present.
      Alternatively, four distinct dorsal vertebrae indicate a minimum of four taxa.
      However, because most taxa are known from single bones, it is likely that small
      bodied theropod diversity remains underestimated. The high abundance of
      allosauroids and basal coelurosaurs (including tyrannosauroids and possibly
      ornithomimosaurs), and the relative rarity of ceratosaurs, is strikingly
      dissimilar to penecontemporaneous dinosaur faunas of Africa and South America,
      which represent an arid, lower-latitude biome. Similarities between dinosaur
      faunas of Victoria and the northern continents concern the proportional
      representatation of higher clades, and may result from the prevailing temperate
      polar climate of Australia, especially at high latitudes in Victoria, which is
      similar to the predominant warm-temperate climate of Laurasia, but distinct from
      the arid climate zone that covered extensive areas of Gondwana. Most dinosaur
      groups probably attained a near-cosmopolitan distribution in the Jurassic, prior
      to fragmentation of the Pangaean supercontinent, and some aspects of the hallmark
      'Gondwanan' fauna of South America and Africa may therefore reflect climate
      driven provinciality, not vicariant evolution driven by continental
      fragmentation. However, vicariance may still be detected at lower phylogenetic
      levels.

PMID- 22615917
TI  - Factors associated with late antiretroviral therapy initiation among adults in
      Mozambique.
AB  - BACKGROUND: Despite recent changes to expand the ART eligibility criteria in sub
      Saharan Africa, many patients still initiate ART in the advanced stages of HIV
      infection, which contributes to increased early mortality rates, poor patient
      outcomes, and onward transmission. METHODS: To evaluate individual and clinic
      level factors associated with late ART initiation in Mozambique, we conducted a
      retrospective sex-specific analysis of data from 36,411 adult patients who
      started ART between January 2005 and June 2009 at 25 HIV clinics in Mozambique.
      Late ART initiation was defined as CD4 count<100 cells/uL or WHO stage IV. Mixed
      effects models were used to identify patient- and clinic-level factors associated
      with late ART initiation. RESULTS: The proportion of patients initiating ART late
      decreased from 46% to 37% during 2005-2007, but remained constant (between 37
      33%) from 2007-2009. Of those who initiated ART late (median CD4 = 57 cells/uL),
      5% were known to have died and 54% were lost to clinic within 6 months of ART
      initiation (compared with 2% and 47% among other patients starting ART [median
      CD4 = 192 cells/uL]). In multivariate analysis, female sex and pregnancy at ART
      initiation (AOR(female_not_pregnant_vs._male) = 0.66, 95%CI [0.62-0.69];
      AOR(pregnant_vs._non_pregnant) = 0.60, 95%CI [0.49-0.73]), younger and older age
      (AOR(15-25_vs.26-30) = 0.86, 95%CI [0.79-0.94], AOR(>45_vs.26-30) = 0.72, 95%CI
      [0.67-0.77]), entry into care via PMTCT (AOR(entry_through_PMTCT_vs.VCT) = 0.42,
      95%CI [0.35-0.50]), marital status (AOR(married/in union_vs.single) = 0.87, 95%CI
      [0.83-0.92]), education (AOR(secondary_or_higher_vs.primary) = 0.87, 95%CI [0.83
      0.93]) and year of ART initiation were associated with a lower likelihood of late
      ART initiation. Clinic-level factors independently associated with a lower
      likelihood of late ART initiation included CD4 machine on-site
      (AOR(CD4_machine_onsite_vs.offsite) = 0.83, 95%CI [0.74-0.94]) and presence of
      PMTCT services onsite (AOR = 0.85, 95%CI [0.77-0.93]). CONCLUSION: The risk of
      starting ART late remained persistently high. Efforts are needed to ensure
      identification and enrollment of patients at earlier stages of HIV disease.
      Individual and clinic level factors identified may provide clues for upstream
      structural interventions.

PMID- 22615918
TI  - Identification and characterisation of the early differentiating cells in neural
      differentiation of human embryonic stem cells.
AB  - One of the challenges in studying early differentiation of human embryonic stem
      cells (hESCs) is being able to discriminate the initial differentiated cells from
      the original pluripotent stem cells and their committed progenies. It remains
      unclear how a pluripotent stem cell becomes a lineage-specific cell type during
      early development, and how, or if, pluripotent genes, such as Oct4 and Sox2, play
      a role in this transition. Here, by studying the dynamic changes in the
      expression of embryonic surface antigens, we identified the sequential loss of
      Tra-1-81 and SSEA4 during hESC neural differentiation and isolated a transient
      Tra-1-81(-)/SSEA4(+) (TR-/S4+) cell population in the early stage of neural
      differentiation. These cells are distinct from both undifferentiated hESCs and
      their committed neural progenitor cells (NPCs) in their gene expression profiles
      and response to extracellular signalling; they co-express both the pluripotent
      gene Oct4 and the neural marker Pax6. Furthermore, these TR-/S4+ cells are able
      to produce cells of both neural and non-neural lineages, depending on their
      environmental cues. Our results demonstrate that expression of the pluripotent
      factor Oct4 is progressively downregulated and is accompanied by the gradual
      upregulation of neural genes, whereas the pluripotent factor Sox2 is consistently
      expressed at high levels, indicating that these pluripotent factors may play
      different roles in the regulation of neural differentiation. The identification
      of TR-S4+ cells provides a cell model for further elucidation of the molecular
      mechanisms underlying hESC neural differentiation.

PMID- 22615919
TI  - Clinical severity of beta-thalassaemia/Hb E disease is associated with
      differential activities of the calpain-calpastatin proteolytic system.
AB  - Earlier observations in the literature suggest that proteolytic degradation of
      excess unmatched alpha-globin chains reduces their accumulation and precipitation
      in beta-thalassaemia erythroid precursor cells and have linked this proteolytic
      degradation to the activity of calpain protease. The aim of this study was to
      correlate the activity of calpain and its inhibitor, calpastatin, with different
      degrees of disease severity in beta-thalassaemia. CD34(+) cells were enriched
      from peripheral blood of healthy individuals (control group) and patients with
      mild and severe clinical presentations of beta(0)-thalassaemia/Hb E disease. By
      ex vivo cultivation promoting erythroid cell differentiation for 7 days,
      proerythroblasts, were employed for the functional characterization of the
      calpain-calpastatin proteolytic system. In comparison to the control group,
      enzymatic activity and protein amounts of MU-calpain were found to be more than 3
      fold increased in proerythroblasts from patients with mild clinical symptoms,
      whereas no significant difference was observed in patients with severe clinical
      symptoms. Furthermore, a 1.6-fold decrease of calpastatin activity and 3.2-fold
      accumulation of a 34 kDa calpain-mediated degradation product of calpastatin were
      observed in patients with mild clinical symptoms. The increased activity of
      calpain may be involved in the removal of excess alpha-globin chains contributing
      to a lower degree of disease severity in patients with mild clinical symptoms.

PMID- 22615920
TI  - LGR6 is a high affinity receptor of R-spondins and potentially functions as a
      tumor suppressor.
AB  - BACKGROUND: LGR6 (leucine-rich repeat containing, G protein-coupled receptor 6)
      is a member of the rhodopsin-like seven transmembrane domain receptor superfamily
      with the highest homology to LGR4 and LGR5. LGR6 was found as one of the novel
      genes mutated in colon cancer through total exon sequencing and its promoter
      region is hypermethylated in 20-50% of colon cancer cases. In the skin, LGR6
      marks a population of stem cells that can give rise to all cell lineages.
      Recently, we and others demonstrated that LGR4 and LGR5 function as receptors of
      R-spondins to potentiate Wnt/beta-catenin signaling. However, the binding
      affinity and functional response of LGR6 to R-spondins, and the activity of colon
      cancer mutants of LGR6 have not been determined. PRINCIPAL FINDINGS: We found
      that LGR6 also binds and responds to R-spondins 1-3 with high affinity to enhance
      Wnt/beta-catenin signaling through increased LRP6 phosphorylation. Similar to
      LGR4 and LGR5, LGR6 is not coupled to heterotrimeric G proteins or to beta
      arrestin following R-spondin stimulation. Functional and expression analysis of
      three somatic mutations identified in colon cancer samples indicates that one
      mutant fails to bind and respond to R-spondin (loss-of-function), but the other
      two have no significant effect on receptor function. Overexpression of wild-type
      LGR6 in HeLa cells leads to increased cell migration following co-treatment with
      R-spondin1 and Wnt3a when compared to vector control cells or cells
      overexpressing the loss-of-function mutant. CONCLUSIONS: LGR6 is a high affinity
      receptor for R-spondins 1-3 and potentially functions as a tumor suppressor
      despite its positive effect on Wnt/beta-catenin signaling.

PMID- 22615921
TI  - Does S-metolachlor affect the performance of Pseudomonas sp. strain ADP as
      bioaugmentation bacterium for atrazine-contaminated soils?
AB  - Atrazine (ATZ) and S-metolachlor (S-MET) are two herbicides widely used, often as
      mixtures. The present work examined whether the presence of S-MET affects the ATZ
      biodegradation activity of the bioaugmentation bacterium Pseudomonas sp. strain
      ADP in a crop soil. S-MET concentrations were selected for their relevance in
      worst-case scenarios of soil contamination by a commercial formulation containing
      both herbicides. At concentrations representative of application of high doses of
      the formulation (up to 50 ug g(-1) of soil, corresponding to a dose approximately
      50* higher than the recommended field dose (RD)), the presence of pure S-MET
      significantly affected neither bacteria survival (~10(7) initial viable cells g(
      1) of soil) nor its ATZ-mineralization activity. Consistently, biodegradation
      experiments, in larger soil microcosms spiked with 20* or 50 * RD of the double
      formulation and inoculated with the bacterium, revealed ATZ to be rapidly (in up
      to 5 days) and extensively (>96%) removed from the soil. During the 5 days,
      concentration of S-MET decreased moderately to about 60% of the initial, both in
      inoculated and non-inoculated microcosms. Concomitantly, an accumulation of the
      two metabolites S-MET ethanesulfonic acid and S-MET oxanilic acid was found.
      Despite the dissipation of almost all the ATZ from the treated soils, the
      respective eluates were still highly toxic to an aquatic microalgae species,
      being as toxic as those from the untreated soil. We suggest that this high
      toxicity may be due to the S-MET and/or its metabolites remaining in the soil.

PMID- 22615922
TI  - The electrically silent Kv6.4 subunit confers hyperpolarized gating charge
      movement in Kv2.1/Kv6.4 heterotetrameric channels.
AB  - The voltage-gated K(+) (Kv) channel subunit Kv6.4 does not form functional
      homotetrameric channels but co-assembles with Kv2.1 to form functional
      Kv2.1/Kv6.4 heterotetrameric channels. Compared to Kv2.1 homotetramers, Kv6.4
      exerts a ~40 mV hyperpolarizing shift in the voltage-dependence of Kv2.1/Kv6.4
      channel inactivation, without a significant effect on activation gating. However,
      the underlying mechanism of this Kv6.4-induced modulation of Kv2.1 channel
      inactivation, and whether the Kv6.4 subunit participates in the voltage-dependent
      gating of heterotetrameric channels is not well understood. Here we report
      distinct gating charge movement of Kv2.1/Kv6.4 heterotetrameric channels,
      compared to Kv2.1 homotetramers, as revealed by gating current recordings from
      mammalian cells expressing these channels. The gating charge movement of
      Kv2.1/Kv6.4 heterotetrameric channels displayed an extra component around the
      physiological K(+) equilibrium potential, characterized by a second sigmoidal
      relationship of the voltage-dependence of gating charge movement. This distinct
      gating charge displacement reflects movement of the Kv6.4 voltage-sensing domain
      and has a voltage-dependency that matches the hyperpolarizing shift in
      Kv2.1/Kv6.4 channel inactivation. These results provide a mechanistic basis for
      the modulation of Kv2.1 channel inactivation gating kinetics by silent Kv6.4
      subunits.

PMID- 22615923
TI  - Adrenergic alpha-1 pathway is associated with hypertension among Nigerians in a
      pathway-focused analysis.
AB  - BACKGROUND: The pathway-focused association approach offers a hypothesis driven
      alternative to the agnostic genome-wide association study. Here we apply the
      pathway-focused approach to an association study of hypertension, systolic blood
      pressure (SBP), and diastolic blood pressure (DBP) in 1614 Nigerians with genome
      wide data. METHODS AND RESULTS: Testing of 28 pathways with biological relevance
      to hypertension, selected a priori, containing a total of 101 unique genes and
      4,349 unique single-nucleotide polymorphisms (SNPs) showed an association for the
      adrenergic alpha 1 (ADRA1) receptor pathway with hypertension (p<0.0009) and
      diastolic blood pressure (p<0.0007). Within the ADRA1 pathway, the genes PNMT
      (hypertension P(gene)<0.004, DBP P(gene)<0.004, and SBP P(gene)<0.009, and ADRA1B
      (hypertension P(gene)<0.005, DBP P(gene)<0.02, and SBP P(gene)<0.02) displayed
      the strongest associations. Neither ADRA1B nor PNMT could be the sole mediator of
      the observed pathway association as the ADRA1 pathway remained significant after
      removing ADRA1B, and other pathways involving PNMT did not reach pathway
      significance. CONCLUSIONS: We conclude that multiple variants in several genes in
      the ADRA1 pathway led to associations with hypertension and DBP. SNPs in ADRA1B
      and PNMT have not previously been linked to hypertension in a genome-wide
      association study, but both genes have shown associations with hypertension
      through linkage or model organism studies. The identification of moderately
      significant (10(-2)>p>10(-5)) SNPs offers a novel method for detecting the
      "missing heritability" of hypertension. These findings warrant further studies in
      similar and other populations to assess the generalizability of our results, and
      illustrate the potential of the pathway-focused approach to investigate genetic
      variation in hypertension.

PMID- 22615924
TI  - A selective PMCA inhibitor does not prolong the electroolfactogram in mouse.
AB  - BACKGROUND: Within the cilia of vertebrate olfactory receptor neurons, Ca(2+)
      accumulates during odor transduction. Termination of the odor response requires
      removal of this Ca(2+), and prior evidence suggests that both Na(+)/Ca(2+)
      exchange and plasma membrane Ca(2+)-ATPase (PMCA) contribute to this removal.
      PRINCIPAL FINDINGS: In intact mouse olfactory epithelium, we measured the time
      course of termination of the odor-induced field potential. Replacement of mucosal
      Na(+) with Li(+), which reduces the ability of Na(+)/Ca(2+) exchange to expel
      Ca(2+), prolonged the termination as expected. However, treating the epithelium
      with the specific PMCA inhibitor caloxin 1b1 caused no significant increase in
      the time course of response termination. CONCLUSIONS: Under these experimental
      conditions, PMCA does not contribute detectably to the termination of the odor
      response.

PMID- 22615925
TI  - The SAM domain of human TEL2 can abrogate transcriptional output from TEL1 (ETV
      6) and ETS1/ETS2.
AB  - Regulation of gene expression downstream of the Receptor Tyrosine Kinase
      signaling pathway in Drosophila relies on a transcriptional effector network
      featuring two conserved Ets family proteins, Yan and Pointed, known as TEL1
      (ETV6) and ETS1/ETS2, respectively, in mammals. As in Drosophila, both TEL1 and
      ETS1/ETS2 operate as Ras pathway transcriptional effectors and misregulated
      activity of either factor has been implicated in many human leukemias and solid
      tumors. Providing essential regulation to the Drosophila network, direct
      interactions with the SAM domain protein Mae attenuate both Yan-mediated
      repression and PointedP2-mediated transcriptional activation. Given the critical
      contributions of Mae to the Drosophila circuitry, we investigated whether the
      human Ets factors TEL1 and ETS1/ETS2 could be subject to analogous regulation.
      Here we demonstrate that the SAM domain of human TEL2 can inhibit the
      transcriptional activities of ETS1/2 and TEL1. Drosophila Mae can also attenuate
      human ETS1/ETS2 function, suggesting there could be cross-species conservation of
      underlying mechanism. In contrast, Mae is not an effective inhibitor of TEL1,
      suggesting the mode of TEL2SAM-mediated inhibition of TEL1 may be distinct from
      how Drosophila Mae antagonizes Yan. Together our results reveal both further
      similarities and new differences between the mammalian and Drosophila networks
      and more broadly suggest that SAM domain-mediated interactions could provide an
      effective mechanism for modulating output from the TEL1 and ETS1/2 oncogenes.

PMID- 22615926
TI  - Resveratrol exerts dosage and duration dependent effect on human mesenchymal stem
      cell development.
AB  - Studies in the past have illuminated the potential benefit of resveratrol as an
      anticancer (pro-apoptosis) and life-extending (pro-survival) compound. However,
      these two different effects were observed at different concentration ranges.
      Studies of resveratrol in a wide range of concentrations on the same cell type
      are lacking, which is necessary to comprehend its diverse and sometimes
      contradictory cellular effects. In this study, we examined the effects of
      resveratrol on cell self-renewal and differentiation of human mesenchymal stem
      cells (hMSCs), a type of adult stem cells that reside in a number of tissues, at
      concentrations ranging from 0.1 to 10 uM after both short- and long-term
      exposure. Our results reveal that at 0.1 uM, resveratrol promotes cell self
      renewal by inhibiting cellular senescence, whereas at 5 uM or above, resveratrol
      inhibits cell self-renewal by increasing senescence rate, cell doubling time and
      S-phase cell cycle arrest. At 1 uM, its effect on cell self-renewal is minimal
      but after long-term exposure it exerts an inhibitory effect, accompanied with
      increased senescence rate. At all concentrations, resveratrol promotes osteogenic
      differentiation in a dosage dependent manner, which is offset by its inhibitory
      effect on cell self-renewal at high concentrations. On the contrary, resveratrol
      suppresses adipogenic differentiation during short-term exposure but promotes
      this process after long-term exposure. Our study implicates that resveratrol is
      the most beneficial to stem cell development at 0.1 uM and caution should be
      taken in applying resveratrol as an anticancer therapeutic agent or nutraceutical
      supplement due to its dosage dependent effect on hMSCs.

PMID- 22615927
TI  - Distinct roles for neuropilin1 and neuropilin2 during mouse corneal innervation.
AB  - Trigeminal sensory innervation of the cornea is critical for protection and
      synthesis of neuropeptides required for normal vision. Little is known about axon
      guidance during mammalian corneal innervation. In contrast to the chick where a
      pericorneal nerve ring forms via Npn/Sema signaling, mouse corneal axons project
      directly into the presumptive cornea without initial formation of an analogous
      nerve ring. Here we show that during development of the mouse cornea, Npn1 is
      strongly expressed by the trigeminal ganglion whereas Npn2 is expressed at low
      levels. At the same time Sema3A and Sema3F are expressed in distinct patterns in
      the ocular tissues. Npn1(sema-/-) mutant corneas become precociously and
      aberrantly innervated by nerve bundles that project further into the corneal
      stroma. In contrast, stromal innervation was not affected in Npn2(-/-) mutants.
      The corneal epithelium was prematurely innervated in both Npn1(sema-/-) and Npn2(
      /-) mutants. These defects were exacerbated in Npn1(sema-/-);Npn2(-/-) double
      mutants, which in addition showed ectopic innervation of the region between the
      optic cup and lens vesicle. Collectively, our data show that Sema3A/Npn1 and
      Sema3F/Npn2 signaling play distinct roles and both are required for proper
      innervation of the mouse cornea.

PMID- 22615929
TI  - Survival differences among native-born and foreign-born older adults in the
      United States.
AB  - BACKGROUND: Studies show that the U.S. foreign-born population has lower
      mortality than the native-born population before age 65. Until recently, the lack
      of data prohibited reliable comparisons of U.S. mortality by nativity at older
      ages. This study provides reliable estimates of U.S. foreign-born and native-born
      mortality at ages 65 and older at the end of the 20(th) century. Life
      expectancies of the U.S. foreign born are compared to other developed nations and
      the foreign-born contribution to total life expectancy (TLE) in the United States
      is assessed. METHODS: Newly available data from Medicare Part B records linked
      with Social Security Administration files are used to estimate period life tables
      for nearly all U.S. adults aged 65 and older in 1995. Age-specific survival
      differences and life expectancies are examined in 1995 by sex, race, and place of
      birth. RESULTS: Foreign-born men and women had lower mortality at almost every
      age from 65 to 100 compared to native-born men and women. Survival differences by
      nativity were substantially greater for blacks than whites. Foreign-born blacks
      had the longest life expectancy of all population groups (18.73 [95% confidence
      interval {CI}, 18.15-19.30] years at age 65 for men and 22.76 [95% CI, 22.28
      23.23] years at age 65 for women). The foreign-born population increased TLE in
      the United States at older ages, and by international comparison, the U.S.
      foreign born were among the longest-lived persons in the world. CONCLUSION:
      Survival estimates based on reliable Medicare data confirm that foreign-born
      adults have longer life expectancy at older ages than native-born adults in the
      United States.

PMID- 22615928
TI  - A significant but rather mild contribution of T286 autophosphorylation to
      Ca2+/CaM-stimulated CaMKII activity.
AB  - BACKGROUND: Autophosphorylation of the Ca(2+)/calmodulin (CaM)-dependent protein
      kinase II (CaMKII) at T286 generates partially Ca(2+)/CaM-independent
      "autonomous" activity, which is thought to be required for long-term potentiation
      (LTP), a form of synaptic plasticity thought to underlie learning and memory. A
      requirement for T286 autophosphorylation also for efficient Ca(2+)/CaM-stimulated
      CaMKII activity has been described, but remains controversial.
      METHODOLOGY/PRINCIPAL FINDINGS: In order to determine the contribution of T286
      autophosphorylation to Ca(2+)/CaM-stimulated CaMKII activity, the activity of
      CaMKII wild type and its phosphorylation-incompetent T286A mutant was compared.
      As the absolute activity can vary between individual kinase preparations, the
      activity was measured in six different extracts for each kinase (expressed in HEK
      293 cells). Consistent with measurements on purified kinase (from a
      baculovirus/Sf9 cell expression system), CaMKII T286A showed a mildly but
      significantly reduced rate of Ca(2+)/CaM-stimulated phosphorylation for two
      different peptide substrates (to ~75-84% of wild type). Additional slower CaMKII
      autophosphorylation at T305/306 inhibits stimulation by Ca(2+)/CaM, but occurs
      only minimally for CaMKII wild type during CaM-stimulated activity assays. Thus,
      we tested if the T286A mutant may show more extensive inhibitory
      autophosphorylation, which could explain its reduced stimulated activity. By
      contrast, inhibitory autophosphorylation was instead found to be even further
      reduced for the T286A mutant under our assay conditions. On a side note, the
      phospho-T305 antibody showed some basal background immuno-reactivity also with
      non-phosphorylated CaMKII, as indicated by T305/306A mutants.
      CONCLUSIONS/SIGNIFICANCE: These results indicate that Ca(2+)/CaM-stimulated
      CaMKII activity is mildly (~1.2-1.3fold) further increased by additional T286
      autophosphorylation, but that this autophosphorylation is not required for the
      major part of the stimulated activity. This indicates that the phenotype of
      CaMKII T286A mutant mice is indeed due to the lack of autonomous activity, as the
      T286A mutant showed no dramatic reduction in stimulated activity.

PMID- 22615930
TI  - Mechanics regulates fate decisions of human embryonic stem cells.
AB  - Research on human embryonic stem cells (hESCs) has attracted much attention given
      their great potential for tissue regenerative therapy and fundamental
      developmental biology studies. Yet, there is still limited understanding of how
      mechanical signals in the local cellular microenvironment of hESCs regulate their
      fate decisions. Here, we applied a microfabricated micromechanical platform to
      investigate the mechanoresponsive behaviors of hESCs. We demonstrated that hESCs
      are mechanosensitive, and they could increase their cytoskeleton contractility
      with matrix rigidity. Furthermore, rigid substrates supported maintenance of
      pluripotency of hESCs. Matrix mechanics-mediated cytoskeleton contractility might
      be functionally correlated with E-cadherin expressions in cell-cell contacts and
      thus involved in fate decisions of hESCs. Our results highlighted the important
      functional link between matrix rigidity, cellular mechanics, and pluripotency of
      hESCs and provided a novel approach to characterize and understand
      mechanotransduction and its involvement in hESC function.

PMID- 22615932
TI  - Uric acid is more strongly associated with impaired glucose regulation in women
      than in men from the general population: the KORA F4-Study.
AB  - OBJECTIVE: High serum uric acid (UA) levels are associated with the metabolic
      syndrome, type 2 diabetes and cardiovascular disease. It is largely unknown
      whether there are gender-specific differences regarding the association between
      UA and prediabetic states. We examined the possible association between UA levels
      and known as well as newly diagnosed diabetes (NDD), isolated impaired fasting
      glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), and combined
      IFG/IGT in a population-based sample of 32-to-81-year-old men and women. RESEARCH
      DESIGN AND METHODS: An oral glucose tolerance test was carried out in all 2,740
      participants without known diabetes of the Cooperative Health Research in the
      Region of Augsburg (KORA) F4 Study conducted between 2006 and 2008 in Southern
      Germany. Serum UA was analysed by the uricase method. RESULTS: In women after
      multivariable adjustment the associations between UA and i-IFG (OR 1.57, 95% CI
      1.15-2.14), IFG/IGT (OR 1.52, 1.07-2.16), NDD (OR 1.67, 95% CI 1.28-2.17), and
      known diabetes (OR 1.47, 95% CI 1.18-1.82) remained significant, but the
      association with i-IGT (OR 1.14, 95% CI 0.95-1.36) lost significance. In contrast
      in men, after multivariable adjustment there was only a significant association
      between UA levels and i-IFG (OR 1.49, 95% CI 1.21-1.84), all other associations
      were non-significant (i-IGT: OR 1.09, IFG/IGT: OR 1.06, NDD: OR 0.91, known
      diabetes: OR 1.04; all p-values>0.05). CONCLUSIONS: Serum UA concentrations were
      associated with different categories of impaired glucose regulation in
      individuals from the general population, particularly in women. Further studies
      investigating the role of UA in the development of derangements in glucose
      metabolism are needed.

PMID- 22615931
TI  - Algae-produced Pfs25 elicits antibodies that inhibit malaria transmission.
AB  - Subunit vaccines are significantly more expensive to produce than traditional
      vaccines because they are based primarily on recombinant proteins that must be
      purified from the expression system. Despite the increased cost, subunit vaccines
      are being developed because they are safe, effective, and can elicit antibodies
      that confer protection against diseases that are not currently vaccine
      preventable. Algae are an attractive platform for producing subunit vaccines
      because they are relatively inexpensive to grow, genetically tractable, easily
      scaled to large volumes, have a short generation time, and are devoid of
      inflammatory, viral, or prion contaminants often present in other systems. We
      tested whether algal chloroplasts can produce malaria transmission blocking
      vaccine candidates, Plasmodium falciparum surface protein 25 (Pfs25) and 28
      (Pfs28). Antibodies that recognize Pfs25 and Pfs28 disrupt the sexual development
      of parasites within the mosquito midgut, thus preventing transmission of malaria
      from one human host to the next. These proteins have been difficult to produce in
      traditional recombinant systems because they contain tandem repeats of
      structurally complex epidermal growth factor-like domains, which cannot be
      produced in bacterial systems, and because they are not glycosylated, so they
      must be modified for production in eukaryotic systems. Production in algal
      chloroplasts avoids these issues because chloroplasts can fold complex eukaryotic
      proteins and do not glycosylate proteins. Here we demonstrate that algae are the
      first recombinant system to successfully produce an unmodified and aglycosylated
      version of Pfs25 or Pfs28. These antigens are structurally similar to the native
      proteins and antibodies raised to these recombinant proteins recognize Pfs25 and
      Pfs28 from P. falciparum. Furthermore, antibodies to algae-produced Pfs25 bind
      the surface of in-vitro cultured P. falciparum sexual stage parasites and exhibit
      transmission blocking activity. Thus, algae are promising organisms for producing
      cysteine-disulfide-containing malaria transmission blocking vaccine candidate
      proteins.

PMID- 22615933
TI  - Inbreeding avoidance influences the viability of reintroduced populations of
      African wild dogs (Lycaon pictus).
AB  - The conservation of many fragmented and small populations of endangered African
      wild dogs (Lycaon pictus) relies on understanding the natural processes affecting
      genetic diversity, demographics, and future viability. We used extensive
      behavioural, life-history, and genetic data from reintroduced African wild dogs
      in South Africa to (1) test for inbreeding avoidance via mate selection and (2)
      model the potential consequences of avoidance on population persistence. Results
      suggested that wild dogs avoided mating with kin. Inbreeding was rare in natal
      packs, after reproductive vacancies, and between sibling cohorts (observed on
      0.8%, 12.5%, and 3.8% of occasions, respectively). Only one of the six (16.7%)
      breeding pairs confirmed as third-order (or closer) kin consisted of animals that
      were familiar with each other, while no other paired individuals had any prior
      association. Computer-simulated populations allowed to experience inbreeding had
      only a 1.6% probability of extinction within 100 years, whereas all populations
      avoiding incestuous matings became extinct due to the absence of unrelated mates.
      Populations that avoided mating with first-order relatives became extinct after
      63 years compared with persistence of 37 and 19 years for those also prevented
      from second-order and third-order matings, respectively. Although stronger
      inbreeding avoidance maintains significantly more genetic variation, our results
      demonstrate the potentially severe demographic impacts of reduced numbers of
      suitable mates on the future viability of small, isolated wild dog populations.
      The rapid rate of population decline suggests that extinction may occur before
      inbreeding depression is observed.

PMID- 22615934
TI  - SUMOylation of paraflagellar rod protein, PFR1, and its stage-specific
      localization in Trypanosoma cruzi.
AB  - BACKGROUND: The flagellate protozoan parasite, Trypanosoma cruzi, is a causative
      agent of Chagas disease that is transmitted by reduviid bugs to humans. The
      parasite exists in multiple morphological forms in both vector and host, and cell
      differentiation in T. cruzi is tightly associated with stage-specific protein
      synthesis and degradation. However, the specific molecular mechanisms responsible
      for this coordinated cell differentiation are unclear. METHODOLOGY/PRINCIPAL
      FINDINGS: The SUMO conjugation system plays an important role in specific protein
      expression. In T. cruzi, a subset of SUMOlylated protein candidates and the
      nuclear localization of SUMO have been shown. Here, we examined the biological
      roles of SUMO in T. cruzi. Site-directed mutagenesis analysis of SUMO consensus
      motifs within T. cruzi SUMO using a bacterial SUMOylation system revealed that T.
      cruzi SUMO can polymerize. Indirect fluorescence analysis using T. cruzi SUMO
      specific antibody showed the extra-nuclear localization of SUMO on the flagellum
      of epimastigote and metacyclic and bloodstream trypomastigote stages. In the
      short-flagellate intracellular amastigote, an extra-nuclear distribution of SUMO
      is associated with basement of the flagellum and becomes distributed along the
      flagellum as amastigote transforms into trypomastigote. We examined the flagellar
      target protein of SUMO and show that a paraflagellar rod protein, PFR1, is
      SUMOylated. CONCLUSIONS: These findings indicate that SUMOylation is associated
      with flagellar homeostasis throughout the parasite life cycle, which may play an
      important role in differentiation of T. cruzi.

PMID- 22615935
TI  - Decontamination efficiencies of pot-type water purifiers for 131I, 134Cs and
      137Cs in rainwater contaminated during Fukushima Daiichi nuclear disaster.
AB  - Rainwater was contaminated by a large release of radionuclides into the
      environment during the Fukushima Daiichi nuclear disaster. It became a matter of
      concern for Japan when several water purification plants detected 131I
      contamination in the drinking water. In the present study, the decontamination
      efficiency of two easily obtainable commercial water purifiers were examined for
      rainwater contaminated with 131I, 134Cs and 137Cs. The water purifiers removed
      94.2-97.8% of the 131I and 84.2-91.5% of the 134Cs and 137Cs after one
      filtration. Seven filtrations removed 98.2-99.6% of the 131I and over 98.0% of
      the 134Cs and 137Cs. From a practical perspective, over the fourth filtrations
      were not needed because of no significant improvements after the third
      filtration.

PMID- 22615936
TI  - The mir-51 family of microRNAs functions in diverse regulatory pathways in
      Caenorhabditis elegans.
AB  - The mir-51 family of microRNAs (miRNAs) in C. elegans are part of the deeply
      conserved miR-99/100 family. While loss of all six family members (mir-51-56) in
      C. elegans results in embryonic lethality, loss of individual mir-51 family
      members results in a suppression of retarded developmental timing defects
      associated with the loss of alg-1. The mechanism of this suppression of
      developmental timing defects is unknown. To address this, we characterized the
      function of the mir-51 family in the developmental timing pathway. We performed
      genetic analysis and determined that mir-51 family members regulate the
      developmental timing pathway in the L2 stage upstream of hbl-1. Loss of the mir
      51 family member, mir-52, suppressed retarded developmental timing defects
      associated with the loss of let-7 family members and lin-46. Enhancement of
      precocious defects was observed for mutations in lin-14, hbl-1, and mir-48(ve33),
      but not later acting developmental timing genes. Interestingly, mir-51 family
      members showed genetic interactions with additional miRNA-regulated pathways,
      which are regulated by the let-7 and mir-35 family miRNAs, lsy-6, miR-240/786,
      and miR-1. Loss of mir-52 likely does not suppress miRNA-regulated pathways
      through an increase in miRNA biogenesis or miRNA activity. We found no increase
      in the levels of four mature miRNAs, let-7, miR-58, miR-62 or miR-244, in mir-52
      or mir-52/53/54/55/56 mutant worms. In addition, we observed no increase in the
      activity of ectopic lsy-6 in the repression of a downstream target in uterine
      cells in worms that lack mir-52. We propose that the mir-51 family functions
      broadly through the regulation of multiple targets, which have not yet been
      identified, in diverse regulatory pathways in C. elegans.

PMID- 22615937
TI  - Proteomic analysis of S-acylated proteins in human B cells reveals palmitoylation
      of the immune regulators CD20 and CD23.
AB  - S-palmitoylation is a reversible post-translational modification important for
      controlling the membrane targeting and function of numerous membrane proteins
      with diverse roles in signalling, scaffolding, and trafficking. We sought to
      identify novel palmitoylated proteins in B lymphocytes using acyl-biotin exchange
      chemistry, coupled with differential analysis by liquid-chromatography tandem
      mass spectrometry. In total, we identified 57 novel palmitoylated protein
      candidates from human EBV-transformed lymphoid cells. Two of them, namely CD20
      and CD23 (low affinity immunoglobulin epsilon Fc receptor), are immune regulators
      that are effective/potential therapeutic targets for haematological malignancies,
      autoimmune diseases and allergic disorders. Palmitoylation of CD20 and CD23 was
      confirmed by heterologous expression of alanine mutants coupled with
      bioorthogonal metabolic labeling. This study demonstrates a new subset of
      palmitoylated proteins in B cells, illustrating the ubiquitous role of protein
      palmitoylation in immune regulation.

PMID- 22615939
TI  - Synchronized audio-visual transients drive efficient visual search for motion-in
      depth.
AB  - In natural audio-visual environments, a change in depth is usually correlated
      with a change in loudness. In the present study, we investigated whether
      correlating changes in disparity and loudness would provide a functional
      advantage in binding disparity and sound amplitude in a visual search paradigm.
      To test this hypothesis, we used a method similar to that used by van der Burg et
      al. to show that non-spatial transient (square-wave) modulations of loudness can
      drastically improve spatial visual search for a correlated luminance modulation.
      We used dynamic random-dot stereogram displays to produce pure disparity
      modulations. Target and distractors were small disparity-defined squares (either
      6 or 10 in total). Each square moved back and forth in depth in front of the
      background plane at different phases. The target's depth modulation was
      synchronized with an amplitude-modulated auditory tone. Visual and auditory
      modulations were always congruent (both sine-wave or square-wave). In a speeded
      search task, five observers were asked to identify the target as quickly as
      possible. Results show a significant improvement in visual search times in the
      square-wave condition compared to the sine condition, suggesting that transient
      auditory information can efficiently drive visual search in the disparity domain.
      In a second experiment, participants performed the same task in the absence of
      sound and showed a clear set-size effect in both modulation conditions. In a
      third experiment, we correlated the sound with a distractor instead of the
      target. This produced longer search times, indicating that the correlation is not
      easily ignored.

PMID- 22615938
TI  - In situ identification of plant-invasive bacteria with MALDI-TOF mass
      spectrometry.
AB  - Rhizobia form a disparate collection of soil bacteria capable of reducing
      atmospheric nitrogen in symbiosis with legumes. The study of rhizobial
      populations in nature involves the collection of large numbers of nodules found
      on roots or stems of legumes, and the subsequent typing of nodule bacteria. To
      avoid the time-consuming steps of isolating and cultivating nodule bacteria prior
      to genotyping, a protocol of strain identification based on the comparison of
      MALDI-TOF MS spectra was established. In this procedure, plant nodules were
      considered as natural bioreactors that amplify clonal populations of nitrogen
      fixing bacteroids. Following a simple isolation procedure, bacteroids were
      fingerprinted by analysing biomarker cellular proteins of 3 to 13 kDa using
      Matrix Assisted Laser Desorption/Ionization Time of Flight (MALDI-TOF) mass
      spectrometry. In total, bacteroids of more than 1,200 nodules collected from
      roots of three legumes of the Phaseoleae tribe (cowpea, soybean or siratro) were
      examined. Plants were inoculated with pure cultures of a slow-growing
      Bradyrhizobium japonicum strain G49, or either of two closely related and fast
      growing Sinorhizobium fredii strains NGR234 and USDA257, or with mixed
      inoculants. In the fully automatic mode, correct identification of bacteroids was
      obtained for >97% of the nodules, and reached 100% with a minimal manual input in
      processing of spectra. These results showed that MALDI-TOF MS is a powerful tool
      for the identification of intracellular bacteria taken directly from plant
      tissues.

PMID- 22615940
TI  - Caspase inhibition with XIAP as an adjunct to AAV vector gene-replacement
      therapy: improving efficacy and prolonging the treatment window.
AB  - PURPOSE: AAV-mediated gene therapy in the rd10 mouse, with retinal degeneration
      caused by mutation in the rod cyclic guanosine monophosphate phosphodiesterase
      beta-subunit (PDEbeta) gene, produces significant, but transient, rescue of
      photoreceptor structure and function. This study evaluates the ability of AAV
      mediated delivery of X-linked inhibitor of apoptosis (XIAP) to enhance and
      prolong the efficacy of PDEbeta gene-replacement therapy. METHODS: Rd10 mice were
      bred and housed in darkness. Two groups of animals were generated: Group 1
      received sub-retinal AAV5-XIAP or AAV5-GFP at postnatal age (P) 4 or 21 days;
      Group 2 received sub-retinal AAV5-XIAP plus AAV5- PDEbeta, AAV5-GFP plus AAV5-
      PDEbeta, or AAV- PDEbeta alone at age P4 or P21. Animals were maintained for an
      additional 4 weeks in darkness before being moved to a cyclic-light environment.
      A subset of animals from Group 1 received a second sub-retinal injection of AAV8
      733-PDEbeta two weeks after being moved to the light. Histology,
      immunohistochemistry, Western blots, and electroretinograms were performed at
      different times after moving to the light. RESULTS: Injection of AAV5-XIAP alone
      at P4 and 21 resulted in significant slowing of light-induced retinal
      degeneration, as measured by outer nuclear thickness and cell counts, but did not
      result in improved outer segment structure and rhodopsin localization. In
      contrast, co-injection of AAV5-XIAP and AAV5-PDEbeta resulted in increased levels
      of rescue and decreased rates of retinal degeneration compared to treatment with
      AAV5-PDEbeta alone. Mice treated with AAV5-XIAP at P4, but not P21, remained
      responsive to subsequent rescue by AAV8-733-PDEbeta when injected two weeks after
      moving to a light-cycling environment. CONCLUSIONS: Adjunctive treatment with the
      anti-apoptotic gene XIAP confers additive protective effect to gene-replacement
      therapy with AAV5-PDEbeta in the rd10 mouse. In addition, AAV5-XIAP, when given
      early, can increase the age at which gene-replacement therapy remains effective,
      thus effectively prolonging the window of opportunity for therapeutic
      intervention.

PMID- 22615942
TI  - CCR2 acts as scavenger for CCL2 during monocyte chemotaxis.
AB  - BACKGROUND: Leukocyte migration is essential for effective host defense against
      invading pathogens and during immune homeostasis. A hallmark of the regulation of
      this process is the presentation of chemokines in gradients stimulating leukocyte
      chemotaxis via cognate chemokine receptors. For efficient migration, receptor
      responsiveness must be maintained whilst the cells crawl on cell surfaces or on
      matrices along the attracting gradient towards increasing concentrations of
      agonist. On the other hand agonist-induced desensitization and internalization is
      a general paradigm for chemokine receptors which is inconsistent with the
      prolonged migratory capacity. METHODOLOGY/PRINCIPAL FINDINGS: Chemotaxis of
      monocytes was monitored in response to fluorescent CCL2-mCherry by time-lapse
      video microscopy. Uptake of the fluorescent agonist was used as indirect measure
      to follow the endogenous receptor CCR2 expressed on primary human monocytes.
      During chemotaxis CCL2-mCherry becomes endocytosed as cargo of CCR2, however, the
      internalization of CCR2 is not accompanied by reduced responsiveness of the cells
      due to desensitization. CONCLUSIONS/SIGNIFICANCE: During chemotaxis CCR2
      expressed on monocytes internalizes with the bound chemoattractant, but cycles
      rapidly back to the plasma membrane to maintain high responsiveness. Moreover,
      following relocation of the source of attractant, monocytes can rapidly reverse
      their polarization axis organizing a new leading edge along the newly formed
      gradient, suggesting a uniform distribution of highly receptive CCR2 on the
      plasma membrane. The present observations further indicate that during chemotaxis
      CCR2 acts as scavenger consuming the chemokine forming the attracting cue.

PMID- 22615941
TI  - Immunological and regenerative aspects of hepatic mast cells in liver allograft
      rejection and tolerance.
AB  - The precise roles of mast cells in liver allograft rejection and tolerance are
      still unknown. This study aimed to explore the roles of mast cells in immune
      regulation and liver regeneration for tolerance induction by using rat models of
      orthotopic liver transplantation (OLT). Stem cell factor (SCF) and its receptor c
      Kit, which are critical to the migration and development of not only stem cells
      but also mast cells, significantly increased in the tolerogenic livers as
      compared with rejected livers. The significant elevation of mast cell tryptase,
      high-affinity IgE receptor, and histamine suggested the activation of mast cells
      in liver allografts at the tolerogenic phase after OLT. Immunohistochemical
      analysis using confocal microscope clearly showed colocalization of mast cells,
      Foxp3+ Tregs, gammadelta T cells, and recipient-derived hepatic progenitor cells
      with higher expression of SCF, IL-9, IL-10, TGF-beta1, and IL-17 related to
      immunoregulation and liver regeneration in the donor grafts of a tolerogenic OLT
      model. Cross-talk among mast cells and other cells was evaluated by in vitro
      studies demonstrating that syngeneic bone marrow-derived mast cells (BMMCs) co
      cultured with naive splenocytes or primary hepatocytes significantly increased
      the population of splenic gammadelta T cells by mitogen stimulation or by mast
      cell degranulation, and also significantly induced the hepatocyte proliferation,
      respectively. Our results suggested that mast cells in the donor grafts may play
      important roles in the induction/maintenance of immune tolerance and liver
      regeneration resulting in the replacement of hepatic cells from donor to
      recipient.

PMID- 22615943
TI  - Caloric restriction suppresses microglial activation and prevents neuroapoptosis
      following cortical injury in rats.
AB  - Traumatic brain injury (TBI) is a widespread cause of death and a major source of
      adult disability. Subsequent pathological events occurring in the brain after
      TBI, referred to as secondary injury, continue to damage surrounding tissue
      resulting in substantial neuronal loss. One of the hallmarks of the secondary
      injury process is microglial activation resulting in increased cytokine
      production. Notwithstanding that recent studies demonstrated that caloric
      restriction (CR) lasting several months prior to an acute TBI exhibits
      neuroprotective properties, understanding how exactly CR influences secondary
      injury is still unclear. The goal of the present study was to examine whether CR
      (50% of daily food intake for 3 months) alleviates the effects of secondary
      injury on neuronal loss following cortical stab injury (CSI). To this end, we
      examined the effects of CR on the microglial activation, tumor necrosis factor
      alpha (TNF-alpha) and caspase-3 expression in the ipsilateral (injured) cortex of
      the adult rats during the recovery period (from 2 to 28 days) after injury. Our
      results demonstrate that CR prior to CSI suppresses microglial activation,
      induction of TNF-alpha and caspase-3, as well as neurodegeneration following
      injury. These results indicate that CR strongly attenuates the effects of
      secondary injury, thus suggesting that CR may increase the successful outcome
      following TBI.

PMID- 22615945
TI  - Spondin-2 (SPON2), a more prostate-cancer-specific diagnostic biomarker.
AB  - BACKGROUND: Prostate-specific antigen (PSA) screening, although common, has
      recently been called into question. To find prostate cancer (PCa) diagnostic
      biomarkers that can make up for the defects of PSA, we compared the secretomes of
      several benign and PCa cell lines, selected candidate molecules, and then
      confirmed their clinical value. METHODOLOGY/PRINCIPAL FINDINGS: We first
      identified extracellular proteins by two-dimensional gel electrophoresis (2-DE)
      coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      identification. We then validated the secreted proteins on a cellular level, and
      finally determined whether they could be used as PCa diagnostic biomarkers using
      prostate tissue and serum specimens of Chinese volunteers by immunohistostaining
      and sandwich ELISA. We obtained credible extracellular protein 2-DE graphs of
      prostate cell lines. The 5 spots that showed superior repeatability were selected
      for LC-MS/MS analysis, which identified seven candidate molecules. One of the
      candidate molecules, spondin-2 (SPON2), was only expressed in the conditioned
      media (CM) of androgen receptor (AR) positive PCa cell lines. Using tissue
      microarray by immunohistostaining, we found SPON2 to be over-expressed in PCa.
      SPON2 staining was more intense in Gleason score sum 7-8 and in PCa patients with
      metastasis. By receiver operator characteristic (ROC) curve analysis, we found
      that the serum SPON2 level was elevated in PCa patients, showing sensitivity and
      specificity suitable for diagnostic use. We also found that SPON2 could be used
      to identify PCa patients with serum PSA levels no higher than 10 ng/ml from
      healthy elderly men. CONCLUSION/SIGNIFICANCE: SPON2 is a new serum and
      histological diagnostic biomarker for PCa. It can avoid some of the problems of
      PSA testing and was here found to offer relatively high sensitivity and
      specificity relative to PSA.

PMID- 22615944
TI  - Developmental hippocampal neuroplasticity in a model of nicotine replacement
      therapy during pregnancy and breastfeeding.
AB  - RATIONALE: The influence of developmental nicotine exposure on the brain
      represents an important health topic in light of the popularity of nicotine
      replacement therapy (NRT) as a smoking cessation method during pregnancy.
      OBJECTIVES: In this study, we used a model of NRT during pregnancy and
      breastfeeding to explore the consequences of chronic developmental nicotine
      exposure on cerebral neuroplasticity in the offspring. We focused on two dynamic
      lifelong phenomena in the dentate gyrus (DG) of the hippocampus that are highly
      sensitive to the environment: granule cell neurogenesis and long-term
      potentiation (LTP). METHODS: Pregnant rats were implanted with osmotic mini-pumps
      delivering either nicotine or saline solutions. Plasma nicotine and metabolite
      levels were measured in dams and offspring. Corticosterone levels, DG
      neurogenesis (cell proliferation, survival and differentiation) and glutamatergic
      electrophysiological activity were measured in pups. RESULTS: Juvenile (P15) and
      adolescent (P41) offspring exposed to nicotine throughout prenatal and postnatal
      development displayed no significant alteration in DG neurogenesis compared to
      control offspring. However, NRT-like nicotine exposure significantly increased
      LTP in the DG of juvenile offspring as measured in vitro from hippocampal slices,
      suggesting that the mechanisms underlying nicotine-induced LTP enhancement
      previously described in adult rats are already functional in pups. CONCLUSIONS:
      These results indicate that synaptic plasticity is disrupted in offspring
      breastfed by dams passively exposed to nicotine in an NRT-like fashion.

PMID- 22615946
TI  - Pemetrexed plus platinum as the first-line treatment option for advanced non
      small cell lung cancer: a meta-analysis of randomized controlled trials.
AB  - To compare the efficacy and toxicities of pemetrexed plus platinum with other
      platinum regimens in patients with previously untreated advanced non-small cell
      lung cancer (NSCLC). METHODS: A meta-analysis was performed using trials
      identified through PubMed, EMBASE, and Cochrane databases. Two investigators
      independently assessed the quality of the trials and extracted data. The outcomes
      included overall survival (OS), progression-free survival (PFS), response rate
      (RR), and different types of toxicity. Hazard ratios (HRs), odds ratios (ORs) and
      their 95% confidence intervals (CIs) were pooled using RevMan software. RESULTS:
      Four trials involving 2,518 patients with previously untreated advanced NSCLC met
      the inclusion criteria. Pemetrexed plus platinum chemotherapy (PPC) improved
      survival compared with other platinum-based regimens (PBR) in patients with
      advanced NSCLC (HR = 0.91, 95% CI: 0.83-1.00, p = 0.04), especially in those with
      non-squamous histology (HR = 0.87, 95% CI: 0.77-0.98, p = 0.02). No statistically
      significant improvement in either PFS or RR was found in PPC group as compared
      with PBR group (HR = 1.03, 95% CI: 0.94-1.13, p = 0.57; OR = 1.15, 95% CI: 0.95
      1.39, p = 0.15, respectively). Compared with PBR, PPC led to less grade 3-4
      neutropenia and leukopenia but more grade 3-4 nausea. However, hematological
      toxicity analysis revealed significant heterogeneities. CONCLUSION: Our results
      suggest that PPC in the first-line setting leads to a significant survival
      advantage with acceptable toxicities for advanced NSCLC patients, especially
      those with non-squamous histology, as compared with other PRB. PPC could be
      considered as the first-line treatment option for advanced NSCLC patients,
      especially those with non-squamous histology.

PMID- 22615947
TI  - Semi-selective fatty acyl reductases from four heliothine moths influence the
      specific pheromone composition.
AB  - BACKGROUND: Sex pheromones are essential in moth mate communication. Information
      on pheromone biosynthetic genes and enzymes is needed to comprehend the
      mechanisms that contribute to specificity of pheromone signals. Most heliothine
      moths use sex pheromones with (Z)-11-hexadecenal as the major component in
      combination with minor fatty aldehydes and alcohols. In this study we focus on
      four closely related species, Heliothis virescens, Heliothis subflexa,
      Helicoverpa armigera and Helicoverpa assulta, which use (Z)-11-hexadecenal, (Z)-9
      tetradecanal, and (Z)-9-hexadecenal in different ratios in their pheromone blend.
      The components are produced from saturated fatty acid precursors by desaturation,
      beta-oxidation, reduction and oxidation. RESULTS: We analyzed the composition of
      fatty acyl pheromone precursors and correlated it to the pheromone composition.
      Next, we investigated whether the downstream fatty-acyl reduction step modulates
      the ratio of alcohol intermediates before the final oxidation step. By isolating
      and functionally characterizing the Fatty Acyl Reductase (pgFAR) from each
      species we found that the pgFARs were active on a broad set of C8 to C16 fatty
      acyl substrates including the key pheromone precursors, Z9-14, Z9-16 and Z11
      16:acyls. When presenting the three precursors in equal ratios to yeast cultures
      expressing any of the four pgFARs, all reduced (Z)-9-tetradecenoate
      preferentially over (Z)-11-hexadecenoate, and the latter over (Z)-9
      hexadecenoate. Finally, when manipulating the precursor ratios in vitro, we found
      that the pgFARs display small differences in the biochemical activity on various
      substrates. CONCLUSIONS: We conclude that a pgFAR with broad specificity is
      involved in heliothine moth pheromone biosynthesis, functioning as a semi
      selective funnel that produces species-specific alcohol product ratios depending
      on the fatty-acyl precursor ratio in the pheromone gland. This study further
      supports the key role of these in pheromone biosynthesis and emphasizes the
      interplay between the pheromone fatty acyl precursors and the Lepidoptera
      specific pgFARs in shaping the pheromone composition.

PMID- 22615948
TI  - Structural basis for specificity of propeptide-enzyme interaction in barley C1A
      cysteine peptidases.
AB  - C1A cysteine peptidases are synthesized as inactive proenzymes. Activation takes
      place by proteolysis cleaving off the inhibitory propeptide. The inhibitory
      capacity of propeptides from barley cathepsin L and B-like peptidases towards
      commercial and barley cathepsins has been characterized. Differences in
      selectivity have been found for propeptides from L-cathepsins against their
      cognate and non cognate enzymes. Besides, the propeptide from barley cathepsin B
      was not able to inhibit bovine cathepsin B. Modelling of their three-dimensional
      structures suggests that most propeptide inhibitory properties can be explained
      from the interaction between the propeptide and the mature cathepsin structures.
      Their potential use as biotechnological tools is discussed.

PMID- 22615949
TI  - Plasma and muscle myostatin in relation to type 2 diabetes.
AB  - OBJECTIVE: Myostatin is a secreted growth factor expressed in skeletal muscle
      tissue, which negatively regulates skeletal muscle mass. Recent animal studies
      suggest a role for myostatin in insulin resistance. We evaluated the possible
      metabolic role of myostatin in patients with type 2 diabetes and healthy
      controls. DESIGN: 76 patients with type 2 diabetes and 92 control subjects were
      included in the study. They were matched for age, gender and BMI. Plasma samples
      and biopsies from the vastus lateralis muscle were obtained to assess plasma
      myostatin and expression of myostatin in skeletal muscle. RESULTS: Patients with
      type 2 diabetes had higher fasting glucose (8.9 versus 5.1 mmol/L, P<0.001),
      plasma insulin (68.2 versus 47.2 pmol/L, P<0.002) and HOMA2-IR (1.6 versus 0.9,
      P<0.0001) when compared to controls. Patients with type 2 diabetes had 1.4
      (P<0.01) higher levels of muscle myostatin mRNA content than the control
      subjects. Plasma myostatin concentrations did not differ between patients with
      type 2 diabetes and controls. In healthy controls, muscle myostatin mRNA
      correlated with HOMA2-IR (r = 0.30, P<0.01), plasma IL-6 (r = 0.34, P<0.05) and
      VO2 max (r = -0.26, P<0.05), however, no correlations were observed in patients
      with type 2 diabetes. CONCLUSIONS: This study supports the idea that myostatin
      may have a negative effect on metabolism. However, the metabolic effect of
      myostatin appears to be overruled by other factors in patients with type 2
      diabetes.

PMID- 22615950
TI  - Preclinical evaluation of oncolytic vaccinia virus for therapy of canine soft
      tissue sarcoma.
AB  - Virotherapy using oncolytic vaccinia virus (VACV) strains is one promising new
      strategy for canine cancer therapy. In this study we describe the establishment
      of an in vivo model of canine soft tissue sarcoma (CSTS) using the new isolated
      cell line STSA-1 and the analysis of the virus-mediated oncolytic and
      immunological effects of two different Lister VACV LIVP1.1.1 and GLV-1h68 strains
      against CSTS. Cell culture data demonstrated that both tested VACV strains
      efficiently infected and destroyed cells of the canine soft tissue sarcoma line
      STSA-1. In addition, in our new canine sarcoma tumor xenograft mouse model,
      systemic administration of LIVP1.1.1 or GLV-1h68 viruses led to significant
      inhibition of tumor growth compared to control mice. Furthermore, LIVP1.1.1
      mediated therapy resulted in almost complete tumor regression and resulted in
      long-term survival of sarcoma-bearing mice. The replication of the tested VACV
      strains in tumor tissues led to strong oncolytic effects accompanied by an
      intense intratumoral infiltration of host immune cells, mainly neutrophils. These
      findings suggest that the direct viral oncolysis of tumor cells and the virus
      dependent activation of tumor-associated host immune cells could be crucial parts
      of anti-tumor mechanism in STSA-1 xenografts. In summary, the data showed that
      both tested vaccinia virus strains and especially LIVP1.1.1 have great potential
      for effective treatment of CSTS.

PMID- 22615951
TI  - Millipede taxonomy after 250 years: classification and taxonomic practices in a
      mega-diverse yet understudied arthropod group.
AB  - BACKGROUND: The arthropod class Diplopoda is a mega-diverse group comprising
      >12,000 described millipede species. The history of taxonomic research within the
      group is tumultuous and, consequently, has yielded a questionable higher-level
      classification. Few higher-taxa are defined using synapomorphies, and the
      practice of single taxon descriptions lacking a revisionary framework has
      produced many monotypic taxa. Additionally, taxonomic and geographic biases
      render global species diversity estimations unreliable. We test whether the
      ordinal taxa of the Diplopoda are consistent with regards to underlying taxonomic
      diversity, attempt to provide estimates for global species diversity, and examine
      millipede taxonomic effort at a global geographic scale. METHODOLOGY/PRINCIPAL
      FINDINGS: A taxonomic distinctness metric was employed to assess uniformity of
      millipede ordinal taxa. We found that ordinal-level taxa are not uniform and are
      likely overinflated with higher-taxa when compared to related groups. Several
      methods of estimating global species richness were employed (Bayesian, variation
      in taxonomic productivity, extrapolation from nearly fully described taxa). Two
      of the three methods provided estimates ranging from 13,413-16,760 species.
      Variations in geographic diversity show biases to North America and Europe and a
      paucity of works on tropical taxa. CONCLUSIONS/SIGNIFICANCE: Before taxa can be
      used in an extensible way, they must be definable with respect to the diversity
      they contain and the diagnostic characters used to delineate them. The higher
      classification for millipedes is shown to be problematic from a number of
      perspectives. Namely, the ordinal taxa are not uniform in their underlying
      diversity, and millipedes appear to have a disproportionate number of higher
      taxa. Species diversity estimates are unreliable due to inconsistent taxonomic
      effort at temporal, geographic, and phylogenetic scales. Lack of knowledge
      concerning many millipede groups compounds these issues. Diplopods are likely not
      unique in this regard as these issues may persist in many other diverse yet
      poorly studied groups.

PMID- 22615952
TI  - A cohort study of serum bilirubin levels and incident non-alcoholic fatty liver
      disease in middle aged Korean workers.
AB  - BACKGROUND: Serum bilirubin may have potent antioxidant and cytoprotective
      effects. Serum bilirubin levels are inversely associated with several
      cardiovascular and metabolic endpoints, but their association with nonalcoholic
      fatty liver disease (NAFLD) has not been investigated except for a single cross
      sectional study in a pediatric population. We assessed the prospective
      association between serum bilirubin concentrations (total, direct, and indirect)
      and the risk for NAFLD. METHODS AND FINDINGS: We performed a cohort study in
      5,900 Korean men, 30 to 59 years of age, with no evidence of liver disease and no
      major risk factors for liver disease at baseline. Study participants were
      followed in annual or biennial health examinations between 2002 and 2009. The
      presence of fatty liver was determined at each visit by ultrasonography. We
      observed 1,938 incident cases of NAFLD during 28,101.8 person-years of follow-up.
      Increasing levels of serum direct bilirubin were progressively associated with a
      decreasing incidence of NAFLD. In age-adjusted models, the hazard ratio for NAFLD
      comparing the highest to the lowest quartile of serum direct bilirubin levels was
      0.61 (95% CI 0.54-0.68). The association persisted after adjusting for multiple
      metabolic parameters (hazard ratio comparing the highest to the lowest quartile
      0.86, 95% CI 0.76-0.98; P trend = 0.039). Neither serum total nor indirect
      bilirubin levels were significantly associated with the incidence of NAFLD.
      CONCLUSIONS: In this large prospective study, higher serum direct bilirubin
      levels were significantly associated with a lower risk of developing NAFLD, even
      adjusting for a variety of metabolic parameters. Further research is needed to
      elucidate the mechanisms underlying this association and to establish the role of
      serum direct bilirubin as a marker for NAFLD risk.

PMID- 22615953
TI  - The risk of amenorrhea is related to chemotherapy-induced leucopenia in breast
      cancer patients receiving epirubicin and taxane based chemotherapy.
AB  - BACKGROUND: Chemotherapy-induced amenorrhea (CIA) is common in young breast
      cancer patients. The incidence of CIA associated with regimens involving
      epirubicin and taxane was not well known. Furthermore, previous studies suggested
      leucopenia and amenorrhea may reflect inter-individual variations in
      pharmacokinetics. The purpose of this study was to investigate the association
      between leucopenia after first cycle of chemotherapy and CIA in young breast
      cancer patients receiving epirubicin and taxane based chemotherapy. Furthermore,
      the incidence of CIA was also assessed. METHODOLOGY AND PRINCIPAL FINDINGS:
      Between October 2008 and March 2010, 186 consecutive premenopausal patients,
      treated with epirubicin and taxane based chemotherapy, were recruited.
      Information about CIA was collected by telephone and out-patient clinic. Of these
      186 patients, data from 165 patients were included and analyzed. Of all 165
      patients, CIA occurred in 72 patients (43.64%). In multivariate analysis, age
      older than 40 y (OR: 16.10, 95% CI: 6.34-40.88, P<0.001) and previous
      childbearing (OR: 3.17, 95% CI: 1.06-9.47, P = 0.038) were significantly
      associated with probability of CIA. Compared to patients treated without taxane,
      patients treated with taxane-contained regimens did not have a significantly
      higher rate of CIA (P>0.05). The rate of CIA in leucopenia group (52.56%) was
      significantly higher than that in normal leukocyte group (34.62%) (P = 0.024). In
      patients treated with a FEC regimen (cyclophosphamide, epirubicin and 5
      fluorouracil), the rate of CIA in leucopenia group (59.57%) was significantly
      higher than that in normal leukocyte group (36.84%) (P = 0.037). CONCLUSIONS: Age
      at diagnosis and previous childbearing were both found to significantly increase
      the risk of CIA, whereas additional taxane was not associated with increased rate
      of CIA. Importantly, leucopenia after first cycle of chemotherapy was associated
      with increased risk of CIA, which suggested that leucopenia may be an early
      predictor of chemotherapy-induced infertility.

PMID- 22615954
TI  - High-resolution positional tracking for long-term analysis of Drosophila sleep
      and locomotion using the "tracker" program.
AB  - Drosophila melanogaster has been used for decades in the study of circadian
      behavior, and more recently has become a popular model for the study of sleep.
      The classic method for monitoring fly activity involves counting the number of
      infrared beam crosses in individual small glass tubes. Incident recording methods
      such as this can measure gross locomotor activity, but they are unable to provide
      details about where the fly is located in space and do not detect small movements
      (i.e. anything less than half the enclosure size), which could lead to an
      overestimation of sleep and an inaccurate report of the behavior of the fly. This
      is especially problematic if the fly is awake, but is not moving distances that
      span the enclosure. Similarly, locomotor deficiencies could be incorrectly
      classified as sleep phenotypes. To address these issues, we have developed a
      locomotor tracking technique (the "Tracker" program) that records the exact
      location of a fly in real time. This allows for the detection of very small
      movements at any location within the tube. In addition to circadian locomotor
      activity, we are able to collect other information, such as distance, speed, food
      proximity, place preference, and multiple additional parameters that relate to
      sleep structure. Direct comparisons of incident recording and our motion tracking
      application using wild type and locomotor-deficient (CASK-beta null) flies show
      that the increased temporal resolution in the data from the Tracker program can
      greatly affect the interpretation of the state of the fly. This is especially
      evident when a particular condition or genotype has strong effects on the
      behavior, and can provide a wealth of information previously unavailable to the
      investigator. The interaction of sleep with other behaviors can also be assessed
      directly in many cases with this method.

PMID- 22615956
TI  - Evolutionary constraint helps unmask a splicing regulatory region in BRCA1 exon
      11.
AB  - BACKGROUND: Alternative splicing across exon 11 produces several BRCA1 isoforms.
      Their proportion varies during the cell cycle, between tissues and in cancer
      suggesting functional importance of BRCA1 splicing regulation around this exon.
      Although the regulatory elements driving exon 11 splicing have never been
      identified, a selective constraint against synonymous substitutions (silent
      nucleotide variations that do not alter the amino acid residue sequence) in a
      critical region of BRCA1 exon 11 has been reported to be associated with the
      necessity to maintain regulatory sequences. METHODOLOGY/PRINCIPAL FINDINGS: Here
      we have designed a specific minigene to investigate the possibility that this
      bias in synonymous codon usage reflects the need to preserve the BRCA1
      alternative splicing program. We report that in-frame deletions and
      translationally silent nucleotide substitutions in the critical region affect
      splicing regulation of BRCA1 exon 11. CONCLUSIONS/SIGNIFICANCE: Using a hybrid
      minigene approach, we have experimentally validated the hypothesis that the need
      to maintain correct alternative splicing is a selective pressure against
      translationally silent sequence variations in the critical region of BRCA1 exon
      11. Identification of the trans-acting factors involved in regulating exon 11
      alternative splicing will be important in understanding BRCA1-associated
      tumorigenesis.

PMID- 22615955
TI  - The cerebellum link to neuroticism: a volumetric MRI association study in healthy
      volunteers.
AB  - Prior research suggests an association between reduced cerebellar volumes and
      symptoms of depression and anxiety in patients with mood disorders. However,
      whether a smaller volume in itself reflects a neuroanatomical correlate for
      increased susceptibility to develop mood disorders remains unclear. The aim of
      the present study was to examine the relationship between cerebellar volume and
      neurotic personality traits in a non-clinical subject sample. 3T Structural
      magnetic resonance imaging scans were acquired, and trait depression and anxiety
      scales of the revised NEO personality inventory were assessed in thirty-eight
      healthy right-handed volunteers. Results showed that cerebellar volume corrected
      for total brain volume was inversely associated with depressive and anxiety
      related personality traits. Cerebellar gray and white matter contributed equally
      to the observed associations. Our findings extend earlier clinical observations
      by showing that cerebellar volume covaries with neurotic personality traits in
      healthy volunteers. The results may point towards a possible role of the
      cerebellum in the vulnerability to experience negative affect. In conclusion,
      cerebellar volumes may constitute a clinico-neuroanatomical correlate for the
      development of depression- and anxiety-related symptoms.

PMID- 22615957
TI  - Diabetes and pre-diabetes as determined by glycated haemoglobin A1c and glucose
      levels in a developing southern Chinese population.
AB  - BACKGROUND: The American Diabetes Association and World Health Organization have
      recently adopted the HbA1c measurement as one method of diagnostic criteria for
      diabetes. The change in diagnostic criteria has important implications for
      diabetes treatment and prevention. We therefore investigate diabetes using HbA1c
      and glucose criteria together, and assess the prevalent trend in a developing
      southern Chinese population with 85 million residents. METHODS: A stratified
      multistage random sampling method was applied and a representative sample of 3590
      residents 18 years of age or above was obtained in 2010. Each participant
      received a full medical check-up, including measurement of fasting plasma
      glucose, 2-hour post-load plasma glucose, and HbA1c. Information on history of
      diagnosis and treatment of diabetes was collected. The prevalence of diabetes
      obtained from the present survey was compared with the data from the survey in
      2002. RESULTS: The prevalence of diabetes based on both glucose and HbA1c
      measurements was 21.7% (95% CI: 17.4%-26.1%) in 2010, which suggests that more
      than 1 in 5 adult residents were suffering from diabetes in this developing
      population. Only 12.9% (95% CI: 8.3%-17.6%) of diabetic residents were aware of
      their condition. The prevalence of pre-diabetes was 66.3% (95% CI: 62.7%-69.8%).
      The prevalence of diabetes and pre-diabetes which met all the three diagnostic
      thresholds (fast plasma glucose, 2 hour post-load plasma glucose, and HbA1c) was
      3.1% and 5.2%, respectively. Diabetes and pre-diabetes as determined by HbA1c
      measurement had higher vascular risk than those determined by glucose levels. The
      prevalence of diabetes increased from 2.9% (95% CI: 2.0%-3.7%) in 2002 to 13.8%
      (95% CI: 10.2%-17.3%) in 2010 based on the same glucose criteria. CONCLUSIONS:
      Our results show that the diabetes epidemic is accelerating in China. The
      awareness of diabetes is extremely low. The glucose test and HbA1c measurement
      should be used together to increase detection of diabetes and pre-diabetes.

PMID- 22615958
TI  - Insufficient radiofrequency ablation promotes angiogenesis of residual
      hepatocellular carcinoma via HIF-1alpha/VEGFA.
AB  - BACKGROUND: The mechanism of rapid growth of the residual tumor after
      radiofrequency (RF) ablation is poorly understood. In this study, we investigated
      the effect of hyperthermia on HepG2 cells and generated a subline with enhanced
      viability and dys-regulated angiogenesis in vivo, which was used as a model to
      further determine the molecular mechanism of the rapid growth of residual HCC
      after RF ablation. METHODOLOGY/PRINCIPAL FINDINGS: Heat treatment was used to
      establish sublines of HepG2 cells. A subline (HepG2 k) with a relatively higher
      viability and significant heat tolerance was selected. The cellular protein
      levels of VEGFA, HIF-1alpha and p-Akt, VEGFA mRNA and secreted VEGFA were
      measured, and all of these were up-regulated in this subline compared to parental
      HepG2 cells. HIF-1alpha inhibitor YC-1 and VEGFA siRNA inhibited the high
      viability of the subline. The conditioned media from the subline exerted stronger
      pro-angiogenic effects. Bevacizumab, VEGFA siRNA and YC-1 inhibited proangiogenic
      effects of the conditioned media of HepG2 k cells and abolished the difference
      between parental HepG2 cells and HepG2 k cells. For in vivo studies, a nude mouse
      model was used, and the efficacy of bavacizumab was determined. HepG2 k tumor had
      stronger pro-angiogenic effects than parental HepG2 tumor. Bevacizumab could
      inhibit the tumor growth and angiogenesis, and also eliminate the difference in
      tumor growth and angiogenesis between parental HepG2 tumor and HepG2 k tumor in
      vivo. CONCLUSIONS/SIGNIFICANCE: The angiogenesis induced by HIF1alpha/VEGFA
      produced by altered cells after hyperthermia treatment may play an important role
      in the rapid growth of residual HCC after RF ablation. Bevacizumab may be a good
      candidate drug for preventing and treating the process.

PMID- 22615959
TI  - In vivo ultrasound and photoacoustic monitoring of mesenchymal stem cells labeled
      with gold nanotracers.
AB  - Longitudinal monitoring of cells is required in order to understand the role of
      delivered stem cells in therapeutic neovascularization. However, there is not an
      imaging technique that is capable of quantitative, longitudinal assessment of
      stem cell behaviors with high spatial resolution and sufficient penetration
      depth. In this study, in vivo and in vitro experiments were performed to
      demonstrate the efficacy of ultrasound-guided photoacoustic (US/PA) imaging to
      monitor mesenchymal stem cells (MSCs) labeled with gold nanotracers (Au NTs). The
      Au NT labeled MSCs, injected intramuscularly in the lower limb of the Lewis rat,
      were detected and spatially resolved. Furthermore, our quantitative in vitro cell
      studies indicate that US/PA imaging is capable of high detection sensitivity
      (1*104 cells/mL) of the Au NT labeled MSCs. Finally, Au NT labeled MSCs captured
      in the PEGylated fibrin gel system were imaged in vivo, as well as in vitro, over
      a one week time period, suggesting that longitudinal cell tracking using US/PA
      imaging is possible. Overall, Au NT labeling of MSCs and US/PA imaging can be an
      alternative approach in stem cell imaging capable of noninvasive, sensitive,
      quantitative, longitudinal assessment of stem cell behaviors with high spatial
      and temporal resolutions at sufficient depths.

PMID- 22615961
TI  - Slip-flow and heat transfer of a non-newtonian nanofluid in a microtube.
AB  - The slip-flow and heat transfer of a non-Newtonian nanofluid in a microtube is
      theoretically studied. The power-law rheology is adopted to describe the non
      Newtonian characteristics of the flow, in which the fluid consistency coefficient
      and the flow behavior index depend on the nanoparticle volume fraction. The
      velocity profile, volumetric flow rate and local Nusselt number are calculated
      for different values of nanoparticle volume fraction and slip length. The results
      show that the influence of nanoparticle volume fraction on the flow of the
      nanofluid depends on the pressure gradient, which is quite different from that of
      the Newtonian nanofluid. Increase of the nanoparticle volume fraction has the
      effect to impede the flow at a small pressure gradient, but it changes to
      facilitate the flow when the pressure gradient is large enough. This remarkable
      phenomenon is observed when the tube radius shrinks to micrometer scale. On the
      other hand, we find that increase of the slip length always results in larger
      flow rate of the nanofluid. Furthermore, the heat transfer rate of the nanofluid
      in the microtube can be enhanced due to the non-Newtonian rheology and slip
      boundary effects. The thermally fully developed heat transfer rate under constant
      wall temperature and constant heat flux boundary conditions is also compared.

PMID- 22615960
TI  - Cell free expression of hif1alpha and p21 in maternal peripheral blood as a
      marker for preeclampsia and fetal growth restriction.
AB  - Preeclampsia, a severe unpredictable complication of pregnancy, occurs in 6% of
      pregnancies, usually in the second or third trimester. The specific etiology of
      preeclampsia remains unclear, although the pathophysiological hallmark of this
      condition appears to be an inadequate blood supply to the placenta. As a result
      of the impaired placental blood flow, intrauterine growth restriction (IUGR) and
      consequential fetal oxidative stress may occur. Consistent with this view,
      pregnancies complicated by preeclampsia and IUGR are characterized by up
      regulation of key transcriptional regulators of the hypoxic response including,
      hif1alpha and as well as p53 and its target genes. Recently, the presence of
      circulating cell-free fetal RNA has been documented in maternal plasma. We
      speculated that pregnancies complicated by preeclampsia and IUGR, will be
      associated with an abnormal expression of p53 and/or hif1alpha related genes in
      the maternal plasma. Maternal plasma from 113 singleton pregnancies (72 normal
      and 41 complicated pregnancies) and 19 twins (9 normal and 10 complicated
      pregnancies) were collected and cell free RNA was extracted. The expression of 18
      genes was measured by one step real-time RT-PCR and was analyzed for prevalence
      of positive/negative expression levels. Results indicate that, among the genes
      examined, cell free plasma expressions of p21 and hif1alpha were more prevalent
      in pregnancies complicated by hypoxia and/or IUGR (p<0.001). To conclude, we
      present in this manuscript data to support the association between two possible
      surrogate markers of hypoxia and common complications of pregnancy. More work is
      needed in order to implement these findings in clinical practice.

PMID- 22615962
TI  - Distinct genetic lineages of Bactrocera caudata (Insecta: Tephritidae) revealed
      by COI and 16S DNA sequences.
AB  - The fruit fly Bactrocera caudata is a pest species of economic importance in
      Asia. Its larvae feed on the flowers of Cucurbitaceae such as Cucurbita moschata.
      To-date it is distinguished from related species based on morphological
      characters. Specimens of B. caudata from Peninsular Malaysia and Indonesia (Bali
      and Lombok) were analysed using the partial DNA sequences of cytochrome c oxidase
      subunit I (COI) and 16S rRNA genes. Both gene sequences revealed that B. caudata
      from Peninsular Malaysia was distinctly different from B. caudata of Bali and
      Lombok, without common haplotype between them. Phylogenetic analysis revealed two
      distinct clades, indicating distinct genetic lineage. The uncorrected 'p'
      distance for COI sequences between B. caudata of Malaysia-Thailand-China and B.
      caudata of Bali-Lombok was 5.65%, for 16S sequences from 2.76 to 2.99%, and for
      combined COI and 16S sequences 4.45 to 4.46%. The 'p' values are distinctly
      different from intraspecific 'p' distance (0-0.23%). Both the B. caudata lineages
      are distinctly separated from related species in the subgenus Zeugodacus - B.
      ascita, B. scutellata, B. ishigakiensis, B. diaphora, B. tau, B. cucurbitae, and
      B. depressa. Molecular phylogenetic analysis indicates that the B. caudata
      lineages are closely related to B. ascita sp. B, and form a clade with B.
      scutellata, B. ishigakiensis, B. diaphora and B. ascita sp. A. This study
      provides additional baseline for the phylogenetic relationships of Bactrocera
      fruit flies of the subgenus Zeugodacus. Both the COI and 16S genes could be
      useful markers for the molecular differentiation and phylogenetic analysis of
      tephritid fruit flies.

PMID- 22615963
TI  - Cyclosporin A inhibits the influenza virus replication through cyclophilin A
      dependent and -independent pathways.
AB  - The immunosuppressive drug cyclosporin A (CsA) has inhibitory effects on the
      replication of several viruses. The antiviral effects are through targeting the
      interaction between viral proteins and host factor cyclophilin A (CypA). CypA has
      been identified to interact with influenza A virus M1 protein and impair the
      early stage of the viral life cycle. In order to identify the effect of CsA on
      influenza virus replication, a CypA-depleted 293T cell line, which was named as
      293T/CypA-, was constructed. The cytopathic effect (CPE) assay and the growth
      curve results indicated that CsA specifically suppressed the influenza A virus
      replication in a dose-dependent manner. CsA treatment had no effect on the viral
      genome replication and transcription but selectively suppressed the viral
      proteins expression. Further studies indicated that CsA could impair the nuclear
      export of viral mRNA in the absence of CypA. In addition, the antiviral activity
      of CsA was independent of calcineurin signaling. Finally, CsA could enhance the
      binding between CypA and M1. The above results suggested that CsA inhibited the
      replication of influenza A virus through CypA-dependent and -independent
      pathways.

PMID- 22615964
TI  - A rat model of central venous catheter to study establishment of long-term
      bacterial biofilm and related acute and chronic infections.
AB  - Formation of resilient biofilms on medical devices colonized by pathogenic
      microorganisms is a major cause of health-care associated infection. While in
      vitro biofilm analyses led to promising anti-biofilm approaches, little is known
      about their translation to in vivo situations and on host contribution to the in
      vivo dynamics of infections on medical devices. Here we have developed an in vivo
      model of long-term bacterial biofilm infections in a pediatric totally
      implantable venous access port (TIVAP) surgically placed in adult rats. Using non
      invasive and quantitative bioluminescence, we studied TIVAP contamination by
      clinically relevant pathogens, Escherichia coli, Pseudomonas aeruginosa,
      Staphylococcus aureus and Staphylococcus epidermidis, and we demonstrated that
      TIVAP bacterial populations display typical biofilm phenotypes. In our study, we
      showed that immunocompetent rats were able to control the colonization and clear
      the bloodstream infection except for up to 30% that suffered systemic infection
      and death whereas none of the immunosuppressed rats survived the infection.
      Besides, we mimicked some clinically relevant TIVAP associated complications such
      as port-pocket infection and hematogenous route of colonization. Finally, by
      assessing an optimized antibiotic lock therapy, we established that our in vivo
      model enables to assess innovative therapeutic strategies against bacterial
      biofilm infections.

PMID- 22615965
TI  - A genome-wide association study reveals loci influencing height and other
      conformation traits in horses.
AB  - The molecular analysis of genes influencing human height has been notoriously
      difficult. Genome-wide association studies (GWAS) for height in humans based on
      tens of thousands to hundreds of thousands of samples so far revealed ~200 loci
      for human height explaining only 20% of the heritability. In domestic animals
      isolated populations with a greatly reduced genetic heterogeneity facilitate a
      more efficient analysis of complex traits. We performed a genome-wide association
      study on 1,077 Franches-Montagnes (FM) horses using ~40,000 SNPs. Our study
      revealed two QTL for height at withers on chromosomes 3 and 9. The association
      signal on chromosome 3 is close to the LCORL/NCAPG genes. The association signal
      on chromosome 9 is close to the ZFAT gene. Both loci have already been shown to
      influence height in humans. Interestingly, there are very large intergenic
      regions at the association signals. The two detected QTL together explain ~18.2%
      of the heritable variation of height in horses. However, another large fraction
      of the variance for height in horses results from ECA 1 (11.0%), although the
      association analysis did not reveal significantly associated SNPs on this
      chromosome. The QTL region on ECA 3 associated with height at withers was also
      significantly associated with wither height, conformation of legs, ventral border
      of mandible, correctness of gaits, and expression of the head. The region on ECA
      9 associated with height at withers was also associated with wither height,
      length of croup and length of back. In addition to these two QTL regions on ECA 3
      and ECA 9 we detected another QTL on ECA 6 for correctness of gaits. Our study
      highlights the value of domestic animal populations for the genetic analysis of
      complex traits.

PMID- 22615966
TI  - Long-term results and prognostic factors of gastric cancer patients with
      microscopic peritoneal carcinomatosis.
AB  - BACKGROUND: Clinical significance of microscopic peritoneal carcinomatosis
      remained unclear. The aim of this study was to evaluate the prognostic value of
      microscopic peritoneal carcinomatosis in gastric cancer. METHODS: From 1996 to
      2007, 4426 patients underwent gastrectomy for gastric cancer at Fudan University
      Shanghai Cancer Center. The clinical and pathological data were reviewed to
      identify patients with microscopic peritoneal carcinomatosis (group 1). The
      clinicopathological features and prognosis were examined. Additionally, 242 stage
      matched gastric cancer patients without microscopic peritoneal carcinomatosis
      (group 2) and 118 with macroscopic peritoneal carcinomatosis (group 3) were
      selected as control groups. RESULTS: Microscopic peritoneal carcinomatosis was
      found in 121 patients. There were 85 males and 36 females (2.36:1). There was a
      higher incidence rate of large size tumor (>=5 cm) (P = 0.045), Borrmann IV (P =
      0.000), and serosal invasion (P = 0.000) in gastric cancer with microscopic
      peritoneal carcinomatosis compared with the control group. The 5-year survival
      rate of gastric cancer with microscopic peritoneal carcinomatosis was 24%,
      significantly poorer than that of the stage-matched control group but better than
      that of patients with macroscopic peritoneal carcinomatosis. The independent
      prognostic factors identified included pathological stage and operative
      curability. CONCLUSIONS: The presence of microscopic peritoneal carcinomatosis
      was associated with worse prognosis for gastric cancer, but curative surgery
      showed potential to improve prognosis.

PMID- 22615967
TI  - Tregs promote the differentiation of Th17 cells in silica-induced lung fibrosis
      in mice.
AB  - BACKGROUND: Silicosis is an occupational lung disease caused by inhalation of
      silica dust and characterized by lung inflammation and fibrosis. Previous study
      showed that Tregs regulate the process of silicosis by modulating the maintenance
      of immune homeostasis in the lung. Th17 cells share reciprocal developmental
      pathway with Tregs and play a pivotal role in the immunopathogenesis of many lung
      diseases by recruiting and activating neutrophils, but the regulatory function of
      Tregs on Th17 response in silica induced lung fibrosis remains to be explored.
      METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the role of Th17 and IL-17 in the
      development of silicosis and their interaction with Tregs, Treg-depleted mice
      model was generated and exposed to silica to establish experimental model of
      silica-induced lung fibrosis. Here we showed that silica increased Th17 response
      in lung fibrosis. Tregs depletion enhanced the neutrophils accumulation and
      attenuated Th17 response in silica induced lung fibrosis. Both mRNA and protein
      results showed that Tregs exerted its modulatory function on Th17 cells and IL-17
      by regulating TGF-beta1 and IL-1beta. CONCLUSION/SIGNIFICANCE: Our study
      suggested that Tregs could promote Th17 cells differentiation by regulating TGF
      beta1 and IL-1beta in silica induced lung fibrosis of mice, which further the
      understanding of the progress of silicosis and provide a new insight in the
      regulatory mechanism of Th17 by Tregs in lung inflammation.

PMID- 22615970
TI  - Chromosome evolution and genome miniaturization in minifish.
AB  - BACKGROUND: Paedocypris is a newly established genus of fish in Southeast Asia.
      Paedocypris is characterized by several unique features, including a tiny adult
      size (thus named miniature fish or minifish), fragmentary habitats of acidic peat
      blackwater swamps, an unusual reproduction mode and truncated development. These
      peculiarities lend themselves excellent for studying chromosome evolution and
      rapid speciation in vertebrates but also make them highly controversial for the
      phylogenetic position. METHODOLOGY AND PRINCIPAL FINDINGS: We have established an
      organ procedure to prepare chromosome spreads from tiny organs of minifish and
      performed a cytogenetic study on two species of the genus Paedocypris, namely P.
      carbunculus (Pc) and P. sp. "Singkep" (Ps). We found 30 and 34 chromosomes in
      diploid cells of Pc and Ps, respectively, which are unusual in teleost fishes.
      The diploid metaphase has 5 pairs of metacentrics and 7 pairs of subtelocentrics
      in Pc compared to 3 pairs of metacentrics and 11 pairs of subtelocentrics in Ps,
      whereas the haploid metaphase contains 5 metacentrics and 7 subtelocentrics in Pc
      compared to 3 metacentrics and 11 subtelocentrics Ps. Chromosome behavior in
      first meiosis revealed the presence of a chromosomal ring consisting of 2
      metacentrics in Pc, suggesting that centric fusion rather than fission was
      responsible for the karyotypic evolution from Ps to Pc. Flow cytometry revealed
      that Pc had a 45% nuclear staining intensity relative to medaka whose genome is
      700 Mb in size and contains 0.81 pg DNA. The Pc genome should have 315 Mb in
      length and 0.36 pg of DNA, which represent one of the smallest values in
      vertebrates, suggesting genome miniaturization in this organism. CONCLUSIONS: Our
      data demonstrate that gross chromosome rearrangements and genome miniaturization
      have accompanied the evolution of Paedocypris fishes. Our data also place
      Paedocypris outside currently described taxa of the Cypriniformes.

PMID- 22615968
TI  - Salmonella strains isolated from Galapagos iguanas show spatial structuring of
      serovar and genomic diversity.
AB  - It is thought that dispersal limitation primarily structures host-associated
      bacterial populations because host distributions inherently limit transmission
      opportunities. However, enteric bacteria may disperse great distances during food
      borne outbreaks. It is unclear if such rapid long-distance dispersal events
      happen regularly in natural systems or if these events represent an anthropogenic
      exception. We characterized Salmonella enterica isolates from the feces of free
      living Galapagos land and marine iguanas from five sites on four islands using
      serotyping and genomic fingerprinting. Each site hosted unique and nearly
      exclusive serovar assemblages. Genomic fingerprint analysis offered a more
      complex model of S. enterica biogeography, with evidence of both unique strain
      pools and of spatial population structuring along a geographic gradient. These
      findings suggest that even relatively generalist enteric bacteria may be strongly
      dispersal limited in a natural system with strong barriers, such as oceanic
      divides. Yet, these differing results seen on two typing methods also suggests
      that genomic variation is less dispersal limited, allowing for different
      ecological processes to shape biogeographical patterns of the core and flexible
      portions of this bacterial species' genome.

PMID- 22615969
TI  - Reph, a regulator of Eph receptor expression in the Drosophila melanogaster optic
      lobe.
AB  - Receptors of the Eph family of tyrosine kinases and their Ephrin ligands are
      involved in developmental processes as diverse as angiogenesis, axon guidance and
      cell migration. However, our understanding of the Eph signaling pathway is
      incomplete, and could benefit from an analysis by genetic methods. To this end,
      we performed a genetic modifier screen for mutations that affect Eph signaling in
      Drosophila melanogaster. Several dozen loci were identified on the basis of their
      suppression or enhancement of an eye defect induced by the ectopic expression of
      Ephrin during development; many of these mutant loci were found to disrupt visual
      system development. One modifier locus, reph (regulator of eph expression), was
      characterized in molecular detail and found to encode a putative nuclear protein
      that interacts genetically with Eph signaling pathway mutations. Reph is an
      autonomous regulator of Eph receptor expression, required for the graded
      expression of Eph protein and the establishment of an optic lobe axonal
      topographic map. These results reveal a novel component of the regulatory pathway
      controlling expression of eph and identify reph as a novel factor in the
      developing visual system.

PMID- 22615971
TI  - Multiple-locus variable-number tandem-repeat analysis of pathogenic Yersinia
      enterocolitica in China.
AB  - The predominant bioserotypes of pathogenic Yersinia enterocolitica in China are
      2/O: 9 and 3/O: 3; no pathogenic O: 8 strains have been found to date. Multiple
      Locus Variable-Number Tandem-Repeat Analysis (MLVA) based on seven loci was able
      to distinguish 104 genotypes among 218 pathogenic Y. enterocolitica isolates in
      China and from abroad, showing a high resolution. The major pathogenic serogroups
      in China, O: 3 and O: 9, were divided into two clusters based on MLVA genotyping.
      The different distribution of Y. enterocolitica MLVA genotypes maybe due to the
      recent dissemination of specific clones of 2/O: 9 and 3/O: 3 strains in China.
      MLVA was a helpful tool for bacterial pathogen surveillance and investigation of
      pathogenic Y. enterocolitica outbreaks.

PMID- 22615973
TI  - Gestational valproate alters BOLD activation in response to complex social and
      primary sensory stimuli.
AB  - Valproic acid (VPA) has been used clinically as an anticonvulsant medication
      during pregnancy; however, it poses a neurodevelopmental risk due to its high
      teratogenicity. We hypothesized that midgestational (GD) exposure to VPA will
      lead to lasting deficits in social behavior and the processing of social stimuli.
      To test this, animals were given a single IP injection of 600 mg/kg of VPA on GD
      12.5. Starting on postnatal day 2 (PND2), animals were examined for physical and
      behavior abnormalities. Functional MRI studies were carried out after PND60. VPA
      and control animals were given vehicle or a central infusion of a V(1a)
      antagonist 90 minutes before imaging. During imaging sessions, rats were
      presented with a juvenile test male followed by a primary visual stimulus (2 Hz
      pulsed light) to examine the effects of prenatal VPA on neural processing. VPA
      rats showed greater increases in BOLD signal response to the social stimulus
      compared to controls in the temporal cortex, thalamus, midbrain and the
      hypothalamus. Blocking the V(1a) receptor reduced the BOLD response in VPA
      animals only. Neural responses to the visual stimulus, however, were lower in VPA
      animals. Blockade with the V(1a) antagonist did not revert this latter effect.
      Our data suggest that prenatal VPA affects the processing of social stimuli and
      perhaps social memory, partly through a mechanism that may involve vasopressin
      V(1a) neurotransmission.

PMID- 22615972
TI  - Genetic variation in selenoprotein genes, lifestyle, and risk of colon and rectal
      cancer.
AB  - BACKGROUND: Associations between selenium and cancer have directed attention to
      role of selenoproteins in the carcinogenic process. METHODS: We used data from
      two population-based case-control studies of colon (n = 1555 cases, 1956
      controls) and rectal (n = 754 cases, 959 controls) cancer. We evaluated the
      association between genetic variation in TXNRD1, TXNRD2, TXNRD3, C11orf31 (SelH),
      SelW, SelN1, SelS, SepX, and SeP15 with colorectal cancer risk. RESULTS: After
      adjustment for multiple comparisons, several associations were observed. Two SNPs
      in TXNRD3 were associated with rectal cancer (rs11718498 dominant OR 1.42 95% CI
      1.16,1.74 pACT 0.0036 and rs9637365 recessive 0.70 95% CI 0.55,0.90 pACT 0.0208).
      Four SNPs in SepN1 were associated with rectal cancer (rs11247735 recessive OR
      1.30 95% CI 1.04,1.63 pACT 0.0410; rs2072749 GGvsAA OR 0.53 95% CI 0.36,0.80 pACT
      0.0159; rs4659382 recessive OR 0.58 95% CI 0.39,0.86 pACT 0.0247; rs718391
      dominant OR 0.76 95% CI 0.62,0.94 pACT 0.0300). Interaction between these genes
      and exposures that could influence these genes showed numerous significant
      associations after adjustment for multiple comparisons. Two SNPs in TXNRD1 and
      four SNPs in TXNRD2 interacted with aspirin/NSAID to influence colon cancer; one
      SNP in TXNRD1, two SNPs in TXNRD2, and one SNP in TXNRD3 interacted with
      aspirin/NSAIDs to influence rectal cancer. Five SNPs in TXNRD2 and one in SelS,
      SeP15, and SelW1 interacted with estrogen to modify colon cancer risk; one SNP in
      SelW1 interacted with estrogen to alter rectal cancer risk. Several SNPs in this
      candidate pathway influenced survival after diagnosis with colon cancer (SeP15
      and SepX1 increased HRR) and rectal cancer (SepX1 increased HRR). CONCLUSIONS:
      Findings support an association between selenoprotein genes and colon and rectal
      cancer development and survival after diagnosis. Given the interactions observed,
      it is likely that the impact of cancer susceptibility from genotype is modified
      by lifestyle.

PMID- 22615975
TI  - What role do annelid neoblasts play? A comparison of the regeneration patterns in
      a neoblast-bearing and a neoblast-lacking enchytraeid oligochaete.
AB  - The term 'neoblast' was originally coined for a particular type of cell that had
      been observed during annelid regeneration, but is now used to describe the
      pluripotent/totipotent stem cells that are indispensable for planarian
      regeneration. Despite having the same name, however, planarian and annelid
      neoblasts are morphologically and functionally distinct, and many annelid species
      that lack neoblasts can nonetheless substantially regenerate. To further
      elucidate the functions of the annelid neoblasts, a comparison was made between
      the regeneration patterns of two enchytraeid oligochaetes, Enchytraeus japonensis
      and Enchytraeus buchholzi, which possess and lack neoblasts, respectively. In E.
      japonensis, which can reproduce asexually by fragmentation and subsequent
      regeneration, neoblasts are present in all segments except for the eight anterior
      most segments including the seven head-specific segments, and all body fragments
      containing neoblasts can regenerate a complete head and a complete tail,
      irrespective of the region of the body from which they were originally derived.
      In E. japonensis, therefore, no antero-posterior gradient of regeneration ability
      exists in the trunk region. However, when amputation was carried out within the
      head region, where neoblasts are absent, the number of regenerated segments was
      found to be dependent on the level of amputation along the body axis. In E.
      buchholzi, which reproduces only sexually and lacks neoblasts in all segments,
      complete heads were never regenerated and incomplete (hypomeric) heads could be
      regenerated only from the anterior region of the body. Such an antero-posterior
      gradient of regeneration ability was observed for both the anterior and posterior
      regeneration in the whole body of E. buchholzi. These results indicate that the
      presence of neoblasts correlates with the absence of an antero-posterior gradient
      of regeneration ability along the body axis, and suggest that the annelid
      neoblasts are more essential for efficient asexual reproduction than for the
      regeneration of missing body parts.

PMID- 22615974
TI  - Characterization and expression of glutamate dehydrogenase in response to acute
      salinity stress in the Chinese mitten crab, Eriocheir sinensis.
AB  - BACKGROUND: Glutamate dehydrogenase (GDH) is a key enzyme for the synthesis and
      catabolism of glutamic acid, proline and alanine, which are important osmolytes
      in aquatic animals. However, the response of GDH gene expression to salinity
      alterations has not yet been determined in macro-crustacean species.
      METHODOLOGY/PRINCIPAL FINDINGS: GDH cDNA was isolated from Eriocheir sinensis.
      Then, GDH gene expression was analyzed in different tissues from normal crabs and
      the muscle of crabs following transfer from freshwater (control) directly to
      water with salinities of 160/00 and 300/00, respectively. Full-length GDH cDNA is
      2,349 bp, consisting of a 76 bp 5'- untranslated region, a 1,695 bp open reading
      frame encoding 564 amino acids and a 578 bp 3'- untranslated region. E. sinensis
      GDH showed 64-90% identity with protein sequences of mammalian and crustacean
      species. Muscle was the dominant expression source among all tissues tested.
      Compared with the control, GDH expression significantly increased at 6 h in crabs
      transferred to 160/00 and 300/00 salinity, and GDH expression peaked at 48 h and
      12 h, respectively, with levels approximately 7.9 and 8.5 fold higher than the
      control. The free amino acid (FAA) changes in muscle, under acute salinity stress
      (160/00 and 300/00 salinities), correlated with GDH expression levels. Total FAA
      content in the muscle, which was based on specific changes in arginine, proline,
      glycine, alanine, taurine, serine and glutamic acid, tended to increase in crabs
      following transfer to salt water. Among these, arginine, proline and alanine
      increased significantly during salinity acclimation and accounted for the highest
      proportion of total FAA. CONCLUSIONS: E. sinensis GDH is a conserved protein that
      serves important functions in controlling osmoregulation. We observed that higher
      GDH expression after ambient salinity increase led to higher FAA metabolism,
      especially the synthesis of glutamic acid, which increased the synthesis of
      proline and alanine to meet the demand of osmoregulation at hyperosmotic
      conditions.

PMID- 22615976
TI  - Neuron to astrocyte communication via cannabinoid receptors is necessary for
      sustained epileptiform activity in rat hippocampus.
AB  - Astrocytes are integral functional components of synapses, regulating
      transmission and plasticity. They have also been implicated in the pathogenesis
      of epilepsy, although their precise roles have not been comprehensively
      characterized. Astrocytes integrate activity from neighboring synapses by
      responding to neuronally released neurotransmitters such as glutamate and ATP.
      Strong activation of astrocytes mediated by these neurotransmitters can promote
      seizure-like activity by initiating a positive feedback loop that induces
      excessive neuronal discharge. Recent work has demonstrated that astrocytes
      express cannabinoid 1 (CB1) receptors, which are sensitive to endocannabinoids
      released by nearby pyramidal cells. In this study, we tested whether this
      mechanism also contributes to epileptiform activity. In a model of 4
      aminopyridine induced epileptic-like activity in hippocampal slice cultures, we
      show that pharmacological blockade of astrocyte CB1 receptors did not modify the
      initiation, but significantly reduced the maintenance of epileptiform discharge.
      When communication in astrocytic networks was disrupted by chelating astrocytic
      calcium, this CB1 receptor-mediated modulation of epileptiform activity was no
      longer observed. Thus, endocannabinoid signaling from neurons to astrocytes
      represents an additional significant factor in the maintenance of epileptiform
      activity in the hippocampus.

PMID- 22615977
TI  - Wild pigs (Sus scrofa) mediate large-scale edge effects in a lowland tropical
      rainforest in Peninsular Malaysia.
AB  - Edge-effects greatly extend the area of tropical forests degraded through human
      activities. At Pasoh, Peninsular Malaysia, it has been suggested that soil
      disturbance by highly abundant wild pigs (Sus scrofa), which feed in adjacent Oil
      Palm plantations, may have mediated the invasion of Clidemia hirta
      (Melastomataceae) into the diverse tropical lowland rain forest. To investigate
      this hypothesis, we established three 1 km transects from the forest/Oil Palm
      plantation boundary into the forest interior. We recorded the distribution of
      soil disturbance by wild pigs, C. hirta abundance, and environmental variables.
      These data were analyzed using a hierarchical Bayesian model that incorporated
      spatial auto-correlation in the environmental variables. As predicted, soil
      disturbance by wild pigs declined with distance from forest edge and C. hirta
      abundance was correlated with the level of soil disturbance. Importantly there
      was no effect of distance on C. hirta abundance, after controlling for the effect
      of soil disturbance. Clidemia hirta abundance was also correlated with the
      presence of canopy openings, but there was no significant association between the
      occurrence of canopy openings and distance from the edge. Increased levels of
      soil disturbance and C. hirta abundance were still detectable approximately 1 km
      from the edge, demonstrating the potential for exceptionally large-scale animal
      mediated edge effects.

PMID- 22615978
TI  - Plasmodium vivax malaria endemicity in Indonesia in 2010.
AB  - BACKGROUND: Plasmodium vivax imposes substantial morbidity and mortality burdens
      in endemic zones. Detailed understanding of the contemporary spatial distribution
      of this parasite is needed to combat it. We used model based geostatistics (MBG)
      techniques to generate a contemporary map of risk of Plasmodium vivax malaria in
      Indonesia in 2010. METHODS: Plasmodium vivax Annual Parasite Incidence data (2006
      2008) and temperature masks were used to map P. vivax transmission limits. A
      total of 4,658 community surveys of P. vivax parasite rate (PvPR) were identified
      (1985-2010) for mapping quantitative estimates of contemporary endemicity within
      those limits. After error-checking a total of 4,457 points were included into a
      national database of age-standardized 1-99 year old PvPR data. A Bayesian MBG
      procedure created a predicted PvPR(1-99) endemicity surface with uncertainty
      estimates. Population at risk estimates were derived with reference to a 2010
      human population surface. RESULTS: We estimated 129.6 million people in Indonesia
      lived at risk of P. vivax transmission in 2010. Among these, 79.3% inhabited
      unstable transmission areas and 20.7% resided in stable transmission areas. In
      western Indonesia, the predicted P. vivax prevalence was uniformly low. Over 70%
      of the population at risk in this region lived on Java and Bali islands, where
      little malaria transmission occurs. High predicted prevalence areas were observed
      in the Lesser Sundas, Maluku and Papua. In general, prediction uncertainty was
      relatively low in the west and high in the east. CONCLUSION: Most Indonesians
      living with endemic P. vivax experience relatively low risk of infection.
      However, blood surveys for this parasite are likely relatively insensitive and
      certainly do not detect the dormant liver stage reservoir of infection. The
      prospects for P. vivax elimination would be improved with deeper understanding of
      glucose-6-phosphate dehydrogenase deficiency (G6PDd) distribution, anti-relapse
      therapy practices and manageability of P. vivax importation risk, especially in
      Java and Bali.

PMID- 22615979
TI  - Delayed retention of new word-forms is better in children than adults regardless
      of language ability: a factorial two-way study.
AB  - BACKGROUND: Nonword repetition, the ability to retain and repeat unfamiliar
      sequences of phonemes is usually impaired in children with specific language
      impairment (SLI), but it is unclear whether this explains slow language learning.
      Traditional nonword repetition tests involve a single presentation of nonwords
      for immediate repetition. Here we considered whether rate of learning of novel
      phonological sequences was impaired when the same items were presented
      repeatedly. METHODOLOGY/PRINCIPAL FINDINGS: Three complex nonwords were each
      presented for repetition five times in two sessions (A and B) separated by one
      hour. We studied both adults and children from (i) families with a child with SLI
      and (ii) families whose children did not have SLI. This gave a 2*2 design with
      familial SLI as one factor, and age (up to or above 18 years) as the other.
      Overall, participants from families with SLI were poorer at nonword repetition
      than their peers from typical-language families, and there was a trend for
      children with SLI to show less within-session learning than typically developing
      children. However, between-session retention, measured as the difference between
      the last trial from session 1 and the first trial of session 2, showed a
      significant age effect, eta2  =  .139, p  =  .004, regardless of family SLI
      status. Adult participants showed a decrease in score from the last trial of
      session A to the first trial of session B, whereas children maintained their
      level of performance, regardless of whether or not they had SLI.
      CONCLUSIONS/SIGNIFICANCE: Poor nonword repetition in SLI appears to reflect
      inadequate encoding of phonological information, rather than problems retaining
      encoded information. Furthermore, the nonword learning task is consistent with
      the notion of a sensitive period in language learning: Children show better
      retention over a delay for new phonological sequences than adults, regardless of
      overall level of language ability.

PMID- 22615980
TI  - Feasibility of using ultra-high field (7 T) MRI for clinical surgical targeting.
AB  - The advantages of ultra-high magnetic field (7 Tesla) MRI for basic science
      research and neuroscience applications have proven invaluable. Structural and
      functional MR images of the human brain acquired at 7 T exhibit rich information
      content with potential utility for clinical applications. However, (1)
      substantial increases in susceptibility artifacts, and (2) geometrical
      distortions at 7 T would be detrimental for stereotactic surgeries such as deep
      brain stimulation (DBS), which typically use 1.5 T images for surgical planning.
      Here, we explore whether these issues can be addressed, making feasible the use
      of 7 T MRI to guide surgical planning. Twelve patients with Parkinson's disease,
      candidates for DBS, were scanned on a standard clinical 1.5 T MRI and a 7 T MRI
      scanner. Qualitative and quantitative assessments of global and regional
      distortion were evaluated based on anatomical landmarks and transformation matrix
      values. Our analyses show that distances between identical landmarks on 1.5 T vs.
      7 T, in the mid-brain region, were less than one voxel, indicating a successful
      co-registration between the 1.5 T and 7 T images under these specific imaging
      parameter sets. On regional analysis, the central part of the brain showed
      minimal distortion, while inferior and frontal areas exhibited larger distortion
      due to proximity to air-filled cavities. We conclude that 7 T MR images of the
      central brain regions have comparable distortions to that observed on a 1.5 T
      MRI, and that clinical applications targeting structures such as the STN, are
      feasible with information-rich 7 T imaging.

PMID- 22615981
TI  - Francisella tularensis elicits IL-10 via a PGE2-inducible factor, to drive
      macrophage MARCH1 expression and class II down-regulation.
AB  - Francisella tularensis is a bacterial pathogen that uses host-derived PGE2 to
      subvert the host's adaptive immune responses in multiple ways. Francisella
      induced PGE2 acts directly on CD4 T cells to blunt production of IFN-gamma.
      Francisella-induced PGE2 can also elicit production of a >10 kDa soluble host
      factor termed FTMOSN (F. tularensismacrophage supernatant), which acts on IFN
      gamma pre-activated MO to down-regulate MHC class II expression via a ubiquitin
      dependent mechanism, blocking antigen presentation to CD4 T cells. Here, we
      report that FTMOSN-induced down-regulation of MO class II is the result of the
      induction of MARCH1, and that MO expressing MARCH1 "resistant" class II molecules
      are resistant to FTMOSN-induced class II down-regulation. Since PGE2 can induce
      IL-10 production and IL-10 is the only reported cytokine able to induce MARCH1
      expression in monocytes and dendritic cells, these findings suggested that IL-10
      is the active factor in FTMOSN. However, use of IL-10 knockout MO established
      that IL-10 is not the active factor in FTMOSN, but rather that Francisella
      elicited PGE2 drives production of a >10 kDa host factor distinct from IL-10.
      This factor then drives MO IL-10 production to induce MARCH1 expression and the
      resultant class II down-regulation. Since many human pathogens such as Salmonella
      typhi, Mycobacterium tuberculosis and Legionella pneumophila also induce
      production of host PGE2, these results suggest that a yet-to-be-identified PGE2
      inducible host factor capable of inducing IL-10 is central to the immune evasion
      mechanisms of multiple important human pathogens.

PMID- 22615982
TI  - Sexual signalling in Propithecus verreauxi: male "chest badge" and female mate
      choice.
AB  - Communication, an essential prerequisite for sociality, involves the transmission
      of signals. A signal can be defined as any action or trait produced by one
      animal, the sender, that produces a change in the behaviour of another animal,
      the receiver. Secondary sexual signals are often used for mate choice because
      they may inform on a potential partner's quality. Verreaux's sifaka (Propithecus
      verreauxi) is characterized by the presence of two different morphs of males
      (bimorphism), which can show either a stained or clean chest. The chest becomes
      stained by secretions of the sternal gland during throat marking (rubbing throat
      and chest on a vertical substrate while smearing the scent deposition). The role
      of the chest staining in guiding female mate choice was previously hypothesized
      but never demonstrated probably due to the difficulty of observing sifaka
      copulations in the wild. Here we report that stained-chested males had a higher
      throat marking activity than clean-chested males during the mating season, but
      not during the birth season. We found that females copulated more frequently with
      stained-chested males than the clean-chested males. Finally, in agreement with
      the biological market theory, we found that clean-chested males, with a lower
      scent-releasing potential, offered more grooming to females. This "grooming for
      sex" tactic was not completely unsuccessful; in fact, half of the clean-chested
      males copulated with females, even though at low frequency. In conclusion, the
      chest stain, possibly correlated with different cues targeted by females, could
      be one of the parameters which help females in selecting mates.

PMID- 22615983
TI  - Granulocyte colony-stimulating factor protects mice during respiratory virus
      infections.
AB  - A burst in the production of pro-inflammatory molecules characterizes the
      beginning of the host response to infection. Cytokines, chemokines, and growth
      factors work in concert to control pathogen replication and activate innate and
      adaptive immune responses. Granulocyte colony-stimulating factor (G-CSF)
      mobilizes and activates hematopoietic cells from the bone marrow, and it has been
      shown to mediate the generation of effective immunity against bacterial and
      fungal infections. G-CSF is produced at high levels in the lungs during infection
      with influenza and parainfluenza viruses, but its role during these infections is
      unknown. Here we show that during infection of mice with a non-lethal dose of
      influenza or Sendai virus, G-CSF promotes the accumulation of activated Ly6G+
      granulocytes that control the extent of the lung pro-inflammatory response.
      Remarkably, these G-CSF-mediated effects facilitate viral clearance and sustain
      mouse survival.

PMID- 22615984
TI  - Accelerated and improved quantification of lymphocytic choriomeningitis virus
      (LCMV) titers by flow cytometry.
AB  - Lymphocytic choriomeningitis virus (LCMV), a natural murine pathogen, is a member
      of the Arenavirus family, may cause atypical meningitis in humans, and has been
      utilized extensively as a model pathogen for the study of virus-induced disease
      and immune responses. Historically, viral titers have been quantified by a
      standard plaque assay, but for non-cytopathic viruses including LCMV this
      requires lengthy incubation, so results cannot be obtained rapidly. Additionally,
      due to specific technical constraints of the plaque assay including the visual
      detection format, it has an element of subjectivity along with limited
      sensitivity. In this study, we describe the development of a FACS-based assay
      that utilizes detection of LCMV nucleoprotein (NP) expression in infected cells
      to determine viral titers, and that exhibits several advantages over the standard
      plaque assay. We show that the LCMV-NP FACS assay is an objective and
      reproducible detection method that requires smaller sample volumes, exhibits a
      ~20-fold increase in sensitivity to and produces results three times faster than
      the plaque assay. Importantly, when applied to models of acute and chronic LCMV
      infection, the LCMV-NP FACS assay revealed the presence of infectious virus in
      samples that were determined to be negative by plaque assay. Therefore, this
      technique represents an accelerated, enhanced and objective alternative method
      for detection of infectious LCMV that is amenable to adaptation for other viral
      infections as well as high throughput diagnostic platforms.

PMID- 22615985
TI  - Highly sensitive in vitro methods for detection of residual undifferentiated
      cells in retinal pigment epithelial cells derived from human iPS cells.
AB  - Human induced pluripotent stem cells (hiPSCs) possess the capabilities of self
      renewal and differentiation into multiple cell types, and they are free of the
      ethical problems associated with human embryonic stem cells (hESCs). These
      characteristics make hiPSCs a promising choice for future regenerative medicine
      research. There are significant obstacles, however, preventing the clinical use
      of hiPSCs. One of the most obvious safety issues is the presence of residual
      undifferentiated cells that have tumorigenic potential. To locate residual
      undifferentiated cells, in vivo teratoma formation assays have been performed
      with immunodeficient animals, which is both costly and time-consuming. Here, we
      examined three in vitro assay methods to detect undifferentiated cells
      (designated an in vitro tumorigenicity assay): soft agar colony formation assay,
      flow cytometry assay and quantitative real-time polymerase chain reaction assay
      (qRT-PCR). Although the soft agar colony formation assay was unable to detect
      hiPSCs even in the presence of a ROCK inhibitor that permits survival of
      dissociated hiPSCs/hESCs, the flow cytometry assay using anti-TRA-1-60 antibody
      detected 0.1% undifferentiated hiPSCs that were spiked in primary retinal pigment
      epithelial (RPE) cells. Moreover, qRT-PCR with a specific probe and primers was
      found to detect a trace amount of Lin28 mRNA, which is equivalent to that present
      in a mixture of a single hiPSC and 5.0*104 RPE cells. Our findings provide highly
      sensitive and quantitative in vitro assays essential for facilitating safety
      profiling of hiPSC-derived products for future regenerative medicine research.

PMID- 22615986
TI  - Improved tolerance to various abiotic stresses in transgenic sweet potato
      (Ipomoea batatas) expressing spinach betaine aldehyde dehydrogenase.
AB  - Abiotic stresses are critical delimiters for the increased productivity and
      cultivation expansion of sweet potato (Ipomoea batatas), a root crop with
      worldwide importance. The increased production of glycine betaine (GB) improves
      plant tolerance to various abiotic stresses without strong phenotypic changes,
      providing a feasible approach to improve stable yield production under
      unfavorable conditions. The gene encoding betaine aldehyde dehydrogenase (BADH)
      is involved in the biosynthesis of GB in plants, and the accumulation of GB by
      the heterologous overexpression of BADH improves abiotic stress tolerance in
      plants. This study is to improve sweet potato, a GB accumulator, resistant to
      multiple abiotic stresses by promoted GB biosynthesis. A chloroplastic BADH gene
      from Spinacia oleracea (SoBADH) was introduced into the sweet potato cultivar
      Sushu-2 via Agrobacterium-mediated transformation. The overexpression of SoBADH
      in the transgenic sweet potato improved tolerance to various abiotic stresses,
      including salt, oxidative stress, and low temperature. The increased BADH
      activity and GB accumulation in the transgenic plant lines under normal and
      multiple environmental stresses resulted in increased protection against cell
      damage through the maintenance of cell membrane integrity, stronger
      photosynthetic activity, reduced reactive oxygen species (ROS) production, and
      induction or activation of ROS scavenging by the increased activity of free
      radical-scavenging enzymes. The increased proline accumulation and systemic
      upregulation of many ROS-scavenging genes in stress-treated transgenic plants
      also indicated that GB accumulation might stimulate the ROS-scavenging system and
      proline biosynthesis via an integrative mechanism. This study demonstrates that
      the enhancement of GB biosynthesis in sweet potato is an effective and feasible
      approach to improve its tolerance to multiple abiotic stresses without causing
      phenotypic defects. This strategy for trait improvement in sweet potato not only
      stabilizes yield production in normal soils in unpredictable climates but also
      provides a novel germplasm for sweet potato production on marginal lands.

PMID- 22615987
TI  - Molecular and physiological properties associated with zebra complex disease in
      potatoes and its relation with Candidatus Liberibacter contents in psyllid
      vectors.
AB  - Zebra complex (ZC) disease on potatoes is associated with Candidatus Liberibacter
      solanacearum (CLs), an alpha-proteobacterium that resides in the plant phloem and
      is transmitted by the potato psyllid Bactericera cockerelli (Sulc). The name ZC
      originates from the brown striping in fried chips of infected tubers, but the
      whole plants also exhibit a variety of morphological features and symptoms for
      which the physiological or molecular basis are not understood. We determined that
      compared to healthy plants, stems of ZC-plants accumulate starch and more than
      three-fold total protein, including gene expression regulatory factors (e.g.
      cyclophilin) and tuber storage proteins (e.g., patatins), indicating that ZC
      affected stems are reprogrammed to exhibit tuber-like physiological properties.
      Furthermore, the total phenolic content in ZC potato stems was elevated two-fold,
      and amounts of polyphenol oxidase enzyme were also high, both serving to explain
      the ZC-hallmark rapid brown discoloration of air-exposed damaged tissue. Newly
      developed quantitative and/or conventional PCR demonstrated that the percentage
      of psyllids in laboratory colonies containing detectable levels of CLs and its
      titer could fluctuate over time with effects on colony prolificacy, but presumed
      reproduction-associated primary endosymbiont levels remained stable. Potato
      plants exposed in the laboratory to psyllid populations with relatively low-CLs
      content survived while exposure of plants to high-CLs psyllids rapidly culminated
      in a lethal collapse. In conclusion, we identified plant physiological biomarkers
      associated with the presence of ZC and/or CLs in the vegetative potato plant
      tissue and determined that the titer of CLs in the psyllid population directly
      affects the rate of disease development in plants.

PMID- 22615989
TI  - Altered risk-based decision making following adolescent alcohol use results from
      an imbalance in reinforcement learning in rats.
AB  - Alcohol use during adolescence has profound and enduring consequences on decision
      making under risk. However, the fundamental psychological processes underlying
      these changes are unknown. Here, we show that alcohol use produces over-fast
      learning for better-than-expected, but not worse-than-expected, outcomes without
      altering subjective reward valuation. We constructed a simple reinforcement
      learning model to simulate altered decision making using behavioral parameters
      extracted from rats with a history of adolescent alcohol use. Remarkably, the
      learning imbalance alone was sufficient to simulate the divergence in choice
      behavior observed between these groups of animals. These findings identify a
      selective alteration in reinforcement learning following adolescent alcohol use
      that can account for a robust change in risk-based decision making persisting
      into later life.

PMID- 22615990
TI  - An improved test for detecting multiplicative homeostatic synaptic scaling.
AB  - Homeostatic scaling of synaptic strengths is essential for maintenance of network
      "gain", but also poses a risk of losing the distinctions among relative synaptic
      weights, which are possibly cellular correlates of memory storage. Multiplicative
      scaling of all synapses has been proposed as a mechanism that would preserve the
      relative weights among them, because they would all be proportionately adjusted.
      It is crucial for this hypothesis that all synapses be affected identically, but
      whether or not this actually occurs is difficult to determine directly.
      Mathematical tests for multiplicative synaptic scaling are presently carried out
      on distributions of miniature synaptic current amplitudes, but the accuracy of
      the test procedure has not been fully validated. We now show that the existence
      of an amplitude threshold for empirical detection of miniature synaptic currents
      limits the use of the most common method for detecting multiplicative changes.
      Our new method circumvents the problem by discarding the potentially distorting
      subthreshold values after computational scaling. This new method should be useful
      in assessing the underlying neurophysiological nature of a homeostatic synaptic
      scaling transformation, and therefore in evaluating its functional significance.

PMID- 22615988
TI  - Impact of short-term HAART initiated during the chronic stage or shortly post
      exposure on SIV infection of male genital organs.
AB  - BACKGROUND: The male genital tract is suspected to constitute a viral sanctuary
      as persistent HIV shedding is found in the semen of a subset of HIV-infected men
      receiving effective antiretroviral therapy (HAART). The origin of this persistent
      shedding is currently unknown. Phylogenetic studies indicated that HIV in semen
      from untreated men arises from local sources and/or passive diffusion from the
      blood. We previously demonstrated in human and macaque low levels and localized
      infection of several semen-producing organs by HIV/SIV. Using a macaque model,
      this study investigates the impact of short term HAART (2-4 weeks) initiated
      either during the asymptomatic chronic stage or 4 h post-intravenous inoculation
      of SIVmac251 on the infection of male genital organs. METHODOLOGY/PRINCIPAL
      FINDINGS: Short term HAART during the chronic stage decreased blood viral load.
      No major impact of HAART was observed on SIV DNA levels in male genital organs
      using a sensitive nested PCR assay. Using in situ hybridization, SIV RNA+ cells
      were detected in all male genital tract organs from untreated and treated animals
      with undetectable blood viral load following HAART. Infected CD68+ myeloid cells
      and CD3+ T lymphocytes were detected pre- and post-HAART. In contrast, short term
      HAART initiated 4 h post-SIV exposure led to a drastic decrease of the male
      genital tissues infection, although it failed to prevent systemic infection. In
      both cases, HAART tended to decrease the number of CD3+ T cells in the male
      organs. CONCLUSIONS: Our results indicate that the established infection of male
      genital organs is not greatly impacted by short term HAART, whereas the same
      treatment during pre-acute phase of the infection efficiently impairs viral
      dissemination to the male genital tract. Further investigations are now needed to
      determine whether infection of male genital organs is responsible for long term
      persistent HIV shedding in semen despite HAART.

PMID- 22615991
TI  - Notch2 and Notch3 function together to regulate vascular smooth muscle
      development.
AB  - Notch signaling has been implicated in the regulation of smooth muscle
      differentiation, but the precise role of Notch receptors is ill defined. Although
      Notch3 receptor expression is high in smooth muscle, Notch3 mutant mice are
      viable and display only mild defects in vascular patterning and smooth muscle
      differentiation. Notch2 is also expressed in smooth muscle and Notch2 mutant mice
      show cardiovascular abnormalities indicative of smooth muscle defects. Together,
      these findings infer that Notch2 and Notch3 act together to govern vascular
      development and smooth muscle differentiation. To address this hypothesis, we
      characterized the phenotype of mice with a combined deficiency in Notch2 and
      Notch3. Our results show that when Notch2 and Notch3 genes are simultaneously
      disrupted, mice die in utero at mid-gestation due to severe vascular
      abnormalities. Assembly of the vascular network occurs normally as assessed by
      Pecam1 expression, however smooth muscle cells surrounding the vessels are
      grossly deficient leading to vascular collapse. In vitro analysis show that both
      Notch2 and Notch3 robustly activate smooth muscle differentiation genes, and
      Notch3, but not Notch2 is a target of Notch signaling. These data highlight the
      combined actions of the Notch receptors in the regulation of vascular
      development, and suggest that while these receptors exhibit compensatory roles in
      smooth muscle, their functions are not entirely overlapping.

PMID- 22615992
TI  - Thermoregulation of capsule production by Streptococcus pyogenes.
AB  - The capsule of Streptococcus pyogenes serves as an adhesin as well as an anti
      phagocytic factor by binding to CD44 on keratinocytes of the pharyngeal mucosa
      and the skin, the main entry sites of the pathogen. We discovered that S.
      pyogenes HSC5 and MGAS315 strains are further thermoregulated for capsule
      production at a post-transcriptional level in addition to the transcriptional
      regulation by the CovRS two-component regulatory system. When the transcription
      of the hasABC capsular biosynthetic locus was de-repressed through mutation of
      the covRS system, the two strains, which have been used for pathogenesis studies
      in the laboratory, exhibited markedly increased capsule production at sub-body
      temperature. Employing transposon mutagenesis, we found that CvfA, a previously
      identified membrane-associated endoribonuclease, is required for the
      thermoregulation of capsule synthesis. The mutation of the cvfA gene conferred
      increased capsule production regardless of temperature. However, the amount of
      the capsule transcript was not changed by the mutation, indicating that a post
      transcriptional regulator mediates between CvfA and thermoregulated capsule
      production. When we tested naturally occurring invasive mucoid strains, a high
      percentage (11/53, 21%) of the strains exhibited thermoregulated capsule
      production. As expected, the mucoid phenotype of these strains at sub-body
      temperature was due to mutations within the chromosomal covRS genes. Capsule
      thermoregulation that exhibits high capsule production at lower temperatures that
      occur on the skin or mucosal surface potentially confers better capability of
      adhesion and invasion when S. pyogenes penetrates the epithelial surface.

PMID- 22615993
TI  - Identification of novel human damage response proteins targeted through yeast
      orthology.
AB  - Studies in Saccharomyces cerevisiae show that many proteins influence cellular
      survival upon exposure to DNA damaging agents. We hypothesized that human
      orthologs of these S. cerevisiae proteins would also be required for cellular
      survival after treatment with DNA damaging agents. For this purpose, human
      homologs of S. cerevisiae proteins were identified and mapped onto the human
      protein-protein interaction network. The resulting human network was highly
      modular and a series of selection rules were implemented to identify 45
      candidates for human toxicity-modulating proteins. The corresponding transcripts
      were targeted by RNA interference in human cells. The cell lines with depleted
      target expression were challenged with three DNA damaging agents: the alkylating
      agents MMS and 4-NQO, and the oxidizing agent t-BuOOH. A comparison of the
      survival revealed that the majority (74%) of proteins conferred either
      sensitivity or resistance. The identified human toxicity-modulating proteins
      represent a variety of biological functions: autophagy, chromatin modifications,
      RNA and protein metabolism, and telomere maintenance. Further studies revealed
      that MMS-induced autophagy increase the survival of cells treated with DNA
      damaging agents. In summary, we show that damage recovery proteins in humans can
      be identified through homology to S. cerevisiae and that many of the same
      pathways are represented among the toxicity modulators.

PMID- 22615995
TI  - Conjugation of functionalized SPIONs with transferrin for targeting and imaging
      brain glial tumors in rat model.
AB  - Currently, effective and specific diagnostic imaging of brain glioma is a major
      challenge. Nanomedicine plays an essential role by delivering the contrast agent
      in a targeted manner to specific tumor cells, leading to improvement in accurate
      diagnosis by good visualization and specific demonstration of tumor cells. This
      study investigated the preparation and characterization of a targeted MR contrast
      agent, transferrin-conjugated superparamagnetic iron oxide nanoparticles (Tf
      SPIONs), for brain glioma detection. MR imaging showed the obvious contrast
      change of brain glioma before and after administration of Tf-SPIONs in C6 glioma
      rat model in vivo on T2 weighted imaging. Significant contrast enhancement of
      brain glioma could still be clearly seen even 48 h post injection, due to the
      retention of Tf-SPIONs in cytoplasm of tumor cells which was proved by Prussian
      blue staining. Thus, these results suggest that Tf-SPIONs could be a potential
      targeting MR contrast agent for the brain glioma.

PMID- 22615994
TI  - Targeting Cx43 and N-cadherin, which are abnormally upregulated in venous leg
      ulcers, influences migration, adhesion and activation of Rho GTPases.
AB  - BACKGROUND: Venous leg ulcers can be very hard to heal and represent a
      significant medical need with no effective therapeutic treatment currently
      available. PRINCIPAL FINDINGS: In wound edge biopsies from human venous leg
      ulcers we found a striking upregulation of dermal N-cadherin, Zonula Occludens-1
      and the gap junction protein Connexin43 (Cx43) compared to intact skin, and in
      stark contrast to the down-regulation of Cx43 expression seen in acute, healing
      wounds. We targeted the expression of these proteins in 3T3 fibroblasts to
      evaluate their role in venous leg ulcers healing. Knockdown of Cx43 and N
      cadherin, but not Zonula Occludens-1, accelerated cell migration in a scratch
      wound-healing assay. Reducing Cx43 increased Golgi reorientation, whilst
      decreasing cell adhesion and proliferation. Furthermore, Connexin43 and N
      cadherin knockdown led to profound effects on fibroblast cytoskeletal dynamics
      after scratch-wounding. The cells exhibited longer lamelipodial protrusions
      lacking the F-actin belt seen at the leading edge in wounded control cells. This
      phenotype was accompanied by augmented activation of Rac-1 and RhoA GTPases, as
      revealed by Forster Resonance Energy Transfer and pull down experiments.
      CONCLUSIONS: Cx43 and N-cadherin are potential therapeutic targets in the
      promotion of healing of venous leg ulcers, by acting at least in part through
      distinct contributions of cell adhesion, migration, proliferation and
      cytoskeletal dynamics.

PMID- 22615996
TI  - Efficacy, stability, and biosafety of sifuvirtide gel as a microbicide candidate
      against HIV-1.
AB  - Sifuvirtide is a proven effective HIV-1 entry inhibitor and its safety profile
      has been established for systemic administration. The present study evaluated the
      potential of sifuvirtide formulated in a universal gel for topical use as a
      microbicide candidate for preventing sexual transmission of HIV. Our data showed
      that sifuvirtide formulated in HEC gel is effective against HIV-1 B, C subtypes,
      CRF07_BC and CRF01_AE, the latter two recombinants represents the most prevalent
      strains in China. In addition, we demonstrated that sifuvirtide in gel is stable
      for at least 8 weeks even at 40 degrees C, and did not cause the disruption of
      integrity of mucosal epithelial surface, or the up-regulation of inflammatory
      cytokines both in vitro or in vivo. These results suggest that sifuvirtide gel is
      an effective, safe and stable product, and should be further tested as a vaginal
      or rectal microbicide in pre-clinical model or clinical trial for preventing HIV
      sexual transmission.

PMID- 22615997
TI  - Movement behavior of high-heeled walking: how does the nervous system control the
      ankle joint during an unstable walking condition?
AB  - The human locomotor system is flexible and enables humans to move without falling
      even under less than optimal conditions. Walking with high-heeled shoes
      constitutes an unstable condition and here we ask how the nervous system controls
      the ankle joint in this situation? We investigated the movement behavior of high
      heeled and barefooted walking in eleven female subjects. The movement variability
      was quantified by calculation of approximate entropy (ApEn) in the ankle joint
      angle and the standard deviation (SD) of the stride time intervals.
      Electromyography (EMG) of the soleus (SO) and tibialis anterior (TA) muscles and
      the soleus Hoffmann (H-) reflex were measured at 4.0 km/h on a motor driven
      treadmill to reveal the underlying motor strategies in each walking condition.
      The ApEn of the ankle joint angle was significantly higher (p<0.01) during high
      heeled (0.38+/-0.08) than during barefooted walking (0.28+/-0.07). During high
      heeled walking, coactivation between the SO and TA muscles increased towards heel
      strike and the H-reflex was significantly increased in terminal swing by 40%
      (p<0.01). These observations show that high-heeled walking is characterized by a
      more complex and less predictable pattern than barefooted walking. Increased
      coactivation about the ankle joint together with increased excitability of the SO
      H-reflex in terminal swing phase indicates that the motor strategy was changed
      during high-heeled walking. Although, the participants were young, healthy and
      accustomed to high-heeled walking the results demonstrate that that walking on
      high-heels needs to be controlled differently from barefooted walking. We suggest
      that the higher variability reflects an adjusted neural strategy of the nervous
      system to control the ankle joint during high-heeled walking.

PMID- 22615998
TI  - Multiple interferon stimulated genes synergize with the zinc finger antiviral
      protein to mediate anti-alphavirus activity.
AB  - The zinc finger antiviral protein (ZAP) is a host factor that mediates inhibition
      of viruses in the Filoviridae, Retroviridae and Togaviridae families. We
      previously demonstrated that ZAP blocks replication of Sindbis virus (SINV), the
      prototype Alphavirus in the Togaviridae family at an early step prior to
      translation of the incoming genome and that synergy between ZAP and one or more
      interferon stimulated genes (ISGs) resulted in maximal inhibitory activity. The
      present study aimed to identify those ISGs that synergize with ZAP to mediate
      Alphavirus inhibition. Using a library of lentiviruses individually expressing
      more than 350 ISGs, we screened for inhibitory activity in interferon defective
      cells with or without ZAP overexpression. Confirmatory tests of the 23 ISGs
      demonstrating the largest infection reduction in combination with ZAP revealed
      that 16 were synergistic. Confirmatory tests of all potentially synergistic ISGs
      revealed 15 additional ISGs with a statistically significant synergistic effect
      in combination with ZAP. These 31 ISGs are candidates for further mechanistic
      studies. The number and diversity of the identified ZAP-synergistic ISGs lead us
      to speculate that ZAP may play an important role in priming the cell for optimal
      ISG function.

PMID- 22615999
TI  - Molecular epidemiology of HIV-1 transmission in a cohort of HIV-1 concordant
      heterosexual couples from Dakar, Senegal.
AB  - BACKGROUND: A large number of HIV-1 infections in Africa occur in married
      couples. The predominant direction of intracouple transmission and the principal
      external origins of infection remain important issues of debate. METHODS: We
      investigated HIV-1 transmission in 46 HIV-1 concordant positive couples from
      Dakar, Senegal. Intracouple transmission was confirmed by maximum-likelihood
      phylogenetic analysis and pairwise distance comparisons of HIV-1 env gp41
      sequences from both partners. Standardized interview data were used to deduce the
      direction as well as the external sources of the intracouple transmissions.
      RESULTS: Conservative molecular analyses showed linked viruses in 34 (74%)
      couples, unlinked viruses in 6 (13%) couples, and indeterminate results for 6
      (13%) couples. The interview data corresponded completely with the molecular
      analyses: all linked couples reported internal transmission and all unlinked
      couples reported external sources of infection. The majority of linked couples
      (93%) reported the husband as internal source of infection. These husbands most
      frequently (82%) reported an occasional sexual relationship as external source of
      infection. Pairwise comparisons of the CD4 count, antiretroviral therapy status,
      and the proportion of gp41 ambiguous base pairs within transmission pairs
      correlated with the reported order of infection events. CONCLUSIONS: In this
      suburban Senegalese population, a majority of HIV-1 concordant couples showed
      linked HIV-1 transmission with the husband as likely index partner. Our data
      emphasize the risk of married women for acquiring HIV-1 as a result of the
      occasional sexual relationships of their husbands.

PMID- 22616000
TI  - Expanding the hygiene hypothesis: early exposure to infectious agents predicts
      delayed-type hypersensitivity to Candida among children in Kilimanjaro.
AB  - BACKGROUND: Multiple lines of evidence suggest that infections in early life
      prevent the development of pathological immune responses to allergens and
      autoantigens (the hygiene hypothesis). Early infections may also affect later
      immune responses to pathogen antigen. METHODS: To evaluate an association between
      early infections and immune responses to pathogen antigen, delayed-type
      hypersensitivity (DTH) to Candida albicans was evaluated among 283 2- to 7-year
      old children in Kilimanjaro, Tanzania. A questionnaire and physical examination
      were used to characterize variables reflecting early exposure to infectious
      agents (family size, house construction materials, BCG vaccination,
      hospitalization history). Logistic regression was used to evaluate the
      association between early exposure to infectious agents and DTH to C. albicans.
      RESULTS: Triceps skinfold thickness (OR: 1.11; 95% CI: 1.01, 1.22) and age (OR:
      1.27; 95% CI: 1.04, 1.55) were positively associated with DTH to C. albicans.
      Adjusted for age and sex, large family size (OR: 2.81; 95% CI: 1.04, 7.61), BCG
      vaccination scar (OR: 3.10; 95% CI: 1.10, 8.71), and hospitalization during
      infancy with an infectious disease (OR: 4.67; 95% CI: 1.00, 21.74) were
      positively associated with DTH to C. albicans. CONCLUSIONS: Early life infections
      were positively associated with later DTH to C. albicans. This result supports an
      expansion of the hygiene hypothesis to explain not only pathological immune
      responses to allergens, but also appropriate immune responses to pathogens.
      Immune system development may be responsive to early infections as an adaptive
      means to tailor reactivity to the local infectious disease ecology.

PMID- 22616001
TI  - UBR2 of the N-end rule pathway is required for chromosome stability via histone
      ubiquitylation in spermatocytes and somatic cells.
AB  - The N-end rule pathway is a proteolytic system in which its recognition
      components (N-recognins) recognize destabilizing N-terminal residues of short
      lived proteins as an essential element of specific degrons, called N-degrons. The
      RING E3 ligases UBR2 and UBR1 are major N-recognins that share size (200 kDa),
      conserved domains and substrate specificities to N-degrons. Despite the known
      function of the N-end rule pathway in degradation of cytosolic proteins, the
      major phenotype of UBR2-deficient male mice is infertility caused by arrest of
      spermatocytes at meiotic prophase I. UBR2-deficient spermatocytes are impaired in
      transcriptional silencing of sex chromosome-linked genes and ubiquitylation of
      histone H2A. In this study we show that the recruitment of UBR2 to meiotic
      chromosomes spatiotemporally correlates to the induction of chromatin-associated
      ubiquitylation, which is significantly impaired in UBR2-deficient spermatocytes.
      UBR2 functions as a scaffold E3 that promotes HR6B/UbcH2-dependent ubiquitylation
      of H2A and H2B but not H3 and H4, through a mechanism distinct from typical
      polyubiquitylation. The E3 activity of UBR2 in histone ubiquitylation is
      allosterically activated by dipeptides bearing destabilizing N-terminal residues.
      Insufficient monoubiquitylation and polyubiquitylation on UBR2-deficient meiotic
      chromosomes correlate to defects in double strand break (DSB) repair and other
      meiotic processes, resulting in pachytene arrest at stage IV and apoptosis. Some
      of these functions of UBR2 are observed in somatic cells, in which UBR2 is a
      chromatin-binding protein involved in chromatin-associated ubiquitylation upon
      DNA damage. UBR2-deficient somatic cells show an array of chromosomal
      abnormalities, including hyperproliferation, chromosome instability, and
      hypersensitivity to DNA damage-inducing reagents. UBR2-deficient mice enriched in
      C57 background die upon birth with defects in lung expansion and neural
      development. Thus, UBR2, known as the recognition component of a major cellular
      proteolytic system, is associated with chromatin and controls chromatin dynamics
      and gene expression in both germ cells and somatic cells.

PMID- 22616002
TI  - Susceptibility of human lymphoid tissue cultured ex vivo to xenotropic murine
      leukemia virus-related virus (XMRV) infection.
AB  - BACKGROUND: Xenotropic murine leukemia virus-related virus (XMRV) was generated
      after a recombination event between two endogenous murine leukemia viruses during
      the production of a prostate cancer cell line. Although the associations of the
      XMRV infection with human diseases appear unlikely, the XMRV is a retrovirus of
      undefined pathogenic potential, able to replicate in human cells in vitro. Since
      recent studies using animal models for infection have yielded conflicting
      results, we set out an ex vivo model for XMRV infection of human tonsillar tissue
      to determine whether XMRV produced by 22Rv1 cells is able to replicate in human
      lymphoid organs. Tonsil blocks were infected and infection kinetics and its
      pathogenic effects were monitored RESULTS: XMRV, though restricted by APOBEC,
      enters and integrates into the tissue cells. The infection did not result in
      changes of T or B-cells, immune activation, nor inflammatory chemokines.
      Infectious viruses could be recovered from supernatants of infected tonsils by
      reinfecting DERSE XMRV indicator cell line, although these supernatants could not
      establish a new infection in fresh tonsil culture, indicating that in our model,
      the viral replication is controlled by innate antiviral restriction factors.
      CONCLUSIONS: Overall, the replication-competent retrovirus XMRV, present in a
      high number of laboratories, is able to infect human lymphoid tissue and produce
      infectious viruses, even though they were unable to establish a new infection in
      fresh tonsillar tissue. Hereby, laboratories working with cell lines producing
      XMRV should have knowledge and understanding of the potential biological
      biohazardous risks of this virus.

PMID- 22616004
TI  - Evolutionary history of the odd-nosed monkeys and the phylogenetic position of
      the newly described Myanmar snub-nosed monkey Rhinopithecus strykeri.
AB  - Odd-nosed monkeys represent one of the two major groups of Asian colobines. Our
      knowledge about this primate group is still limited as it is highlighted by the
      recent discovery of a new species in Northern Myanmar. Although a common origin
      of the group is now widely accepted, the phylogenetic relationships among its
      genera and species, and the biogeographic processes leading to their current
      distribution are largely unknown. To address these issues, we have analyzed
      complete mitochondrial genomes and 12 nuclear loci, including one X chromosomal,
      six Y chromosomal and five autosomal loci, from all ten odd-nosed monkey species.
      The gene tree topologies and divergence age estimates derived from different
      markers were highly similar, but differed in placing various species or
      haplogroups within the genera Rhinopithecus and Pygathrix. Based on our data,
      Rhinopithecus represent the most basal lineage, and Nasalis and Simias form
      closely related sister taxa, suggesting a Northern origin of odd-nosed monkeys
      and a later invasion into Indochina and Sundaland. According to our divergence
      age estimates, the lineages leading to the genera Rhinopithecus, Pygathrix and
      Nasalis+Simias originated in the late Miocene, while differentiation events
      within these genera and also the split between Nasalis and Simias occurred in the
      Pleistocene. Observed gene tree discordances between mitochondrial and nuclear
      datasets, and paraphylies in the mitochondrial dataset for some species of the
      genera Rhinopithecus and Pygathrix suggest secondary gene flow after the taxa
      initially diverged. Most likely such events were triggered by dramatic changes in
      geology and climate within the region. Overall, our study provides the most
      comprehensive view on odd-nosed monkey evolution and emphasizes that data from
      differentially inherited markers are crucial to better understand evolutionary
      relationships and to trace secondary gene flow.

PMID- 22616003
TI  - Pretubulysin: from hypothetical biosynthetic intermediate to potential lead in
      tumor therapy.
AB  - Pretubulysin is a natural product that is found in strains of myxobacteria in
      only minute amounts. It represents the first enzyme-free intermediate in the
      biosynthesis of tubulysins and undergoes post-assembly acylation and oxidation
      reactions. Pretubulysin inhibits the growth of cultured mammalian cells, as do
      tubulysins, which are already in advanced preclinical development as anticancer
      and antiangiogenic agents. The mechanism of action of this highly potent compound
      class involves the depolymerization of microtubules, thereby inducing mitotic
      arrest. Supply issues with naturally occurring derivatives can now be
      circumvented by the total synthesis of pretubulysin, which, in contrast to
      tubulysin, is synthetically accessible in gram-scale quantities. We show that the
      simplified precursor is nearly equally potent to the parent compound.
      Pretubulysin induces apoptosis and inhibits cancer cell migration and tubulin
      assembly in vitro. Consequently, pretubulysin appears to be an ideal candidate
      for future development in preclinical trials and is a very promising early lead
      structure in cancer therapy.

PMID- 22616005
TI  - Insect eggs can enhance wound response in plants: a study system of tomato
      Solanum lycopersicum L. and Helicoverpa zea Boddie.
AB  - Insect oviposition on plants frequently precedes herbivory. Accumulating evidence
      indicates that plants recognize insect oviposition and elicit direct or indirect
      defenses to reduce the pressure of future herbivory. Most of the oviposition
      triggered plant defenses described thus far remove eggs or keep them away from
      the host plant or their desirable feeding sites. Here, we report induction of
      antiherbivore defense by insect oviposition which targets newly hatched larvae,
      not the eggs, in the system of tomato Solanum lycopersicum L., and tomato
      fruitworm moth Helicoverpa zea Boddie. When tomato plants were oviposited by H.
      zea moths, pin2, a highly inducible gene encoding protease inhibitor2, which is a
      representative defense protein against herbivorous arthropods, was expressed at
      significantly higher level at the oviposition site than surrounding tissues, and
      expression decreased with distance away from the site of oviposition. Moreover,
      more eggs resulted in higher pin2 expression in leaves, and both fertilized and
      unfertilized eggs induced pin2 expression. Notably, when quantified daily
      following deposition of eggs, pin2 expression at the oviposition site was highest
      just before the emergence of larvae. Furthermore, H. zea oviposition primed the
      wound-induced increase of pin2 transcription and a burst of jasmonic acid (JA);
      tomato plants previously exposed to H. zea oviposition showed significantly
      stronger induction of pin2 and higher production of JA upon subsequent simulated
      herbivory than without oviposition. Our results suggest that tomato plants
      recognize H. zea oviposition as a signal of impending future herbivory and induce
      defenses to prepare for this herbivory by newly hatched neonate larvae.

PMID- 22616006
TI  - Tetrahydrouridine inhibits cell proliferation through cell cycle regulation
      regardless of cytidine deaminase expression levels.
AB  - Tetrahydrouridine (THU) is a well characterized and potent inhibitor of cytidine
      deaminase (CDA). Highly expressed CDA catalyzes and inactivates cytidine
      analogues, ultimately contributing to increased gemcitabine resistance.
      Therefore, a combination therapy of THU and gemcitabine is considered to be a
      potential and promising treatment for tumors with highly expressed CDA. In this
      study, we found that THU has an alternative mechanism for inhibiting cell growth
      which is independent of CDA expression. Three different carcinoma cell lines
      (MIAPaCa-2, H441, and H1299) exhibited decreased cell proliferation after sole
      administration of THU, while being unaffected by knocking down CDA. To
      investigate the mechanism of THU-induced cell growth inhibition, cell cycle
      analysis using flow cytometry was performed. This analysis revealed that THU
      caused an increased rate of G1-phase occurrence while S-phase occurrence was
      diminished. Similarly, Ki-67 staining further supported that THU reduces cell
      proliferation. We also found that THU regulates cell cycle progression at the
      G1/S checkpoint by suppressing E2F1. As a result, a combination regimen of THU
      and gemcitabine might be a more effective therapy than previously believed for
      pancreatic carcinoma since THU works as a CDA inhibitor, as well as an inhibitor
      of cell growth in some types of pancreatic carcinoma cells.

PMID- 22616007
TI  - The role of visual information in numerosity estimation.
AB  - Mainstream theory suggests that the approximate number system supports our non
      symbolic number abilities (e.g. estimating or comparing different sets of items).
      It is argued that this system can extract number independently of the visual cues
      present in the stimulus (diameter, aggregate surface, etc.). However, in a recent
      report we argue that this might not be the case. We showed that participants
      combined information from different visual cues to derive their answers. While
      numerosity comparison requires a rough comparison of two sets of items (smaller
      versus larger), numerosity estimation requires a more precise mechanism. It could
      therefore be that numerosity estimation, in contrast to numerosity comparison,
      might rely on the approximate number system. To test this hypothesis, we
      conducted a numerosity estimation experiment. We controlled for the visual cues
      according to current standards: each single visual property was not informative
      about numerosity. Nevertheless, the results reveal that participants were
      influenced by the visual properties of the dot arrays. They gave a larger
      estimate when the dot arrays consisted of dots with, on average, a smaller
      diameter, aggregate surface or density but a larger convex hull. The reliance on
      visual cues to estimate numerosity suggests that the existence of an approximate
      number system that can extract numerosity independently of the visual cues is
      unlikely. Instead, we propose that humans estimate numerosity by weighing the
      different visual cues present in the stimuli.

PMID- 22616008
TI  - The role of the Yap5 transcription factor in remodeling gene expression in
      response to Fe bioavailability.
AB  - The budding yeast Saccharomyces cerevisiae has developed several mechanisms to
      avoid either the drastic consequences of iron deprivation or the toxic effects of
      iron excess. In this work, we analysed the global gene expression changes
      occurring in yeast cells undergoing iron overload. Several genes directly or
      indirectly involved in iron homeostasis showed altered expression and the
      relevance of these changes are discussed. Microarray analyses were also performed
      to identify new targets of the iron responsive factor Yap5. Besides the iron
      vacuolar transporter CCC1, Yap5 also controls the expression of glutaredoxin
      GRX4, previously known to be involved in the regulation of Aft1 nuclear
      localization. Consistently, we show that in the absence of Yap5 Aft1 nuclear
      exclusion is slightly impaired. These studies provide further evidence that cells
      control iron homeostasis by using multiple pathways.

PMID- 22616009
TI  - Evidence of coexistence of C3 and C4 photosynthetic pathways in a green-tide
      forming alga, Ulva prolifera.
AB  - Ulva prolifera, a typical green-tide-forming alga, can accumulate a large biomass
      in a relatively short time period, suggesting that photosynthesis in this
      organism, particularly its carbon fixation pathway, must be very efficient. Green
      algae are known to generally perform C3 photosynthesis, but recent metabolic
      labeling and genome sequencing data suggest that they may also perform C4
      photosynthesis, so C4 photosynthesis might be more wide-spread than previously
      anticipated. Both C3 and C4 photosynthesis genes were found in U. prolifera by
      transcriptome sequencing. We also discovered the key enzymes of C4 metabolism
      based on functional analysis, such as pyruvate orthophosphate dikinase (PPDK),
      phosphoenolpyruvate carboxylase (PEPC), and phosphoenolpyruvate carboxykinase
      (PCK). To investigate whether the alga operates a C4-like pathway, the expression
      of rbcL and PPDK and their enzyme activities were measured under various forms
      and intensities of stress (differing levels of salinity, light intensity, and
      temperature). The expression of rbcL and PPDK and their enzyme activities were
      higher under adverse circumstances. However, under conditions of desiccation, the
      expression of rbcL and ribulose-1, 5-biphosphate carboxylase (RuBPCase) activity
      was lower, whereas that of PPDK was higher. These results suggest that elevated
      PPDK activity may alter carbon metabolism and lead to a partial operation of C4
      type carbon metabolism in U. prolifera, probably contributing to its wide
      distribution and massive, repeated blooms in the Yellow Sea.

PMID- 22616010
TI  - A meta-analysis of caspase 9 polymorphisms in promoter and exon sequence on
      cancer susceptibility.
AB  - BACKGROUND: Caspases are important regulators and executioners in apoptosis
      pathway and have been defined as either tumor suppressors or oncogenes.
      Polymorphisms in promoter and exon of caspase 9 were shown to confer genetic
      susceptibility to multiple cancers, but the results were inconsistent. To
      accomplish a more precise estimation of the relationship, a meta-analysis was
      performed. METHODOLOGY/PRINCIPAL FINDINGS: We assessed published studies of the
      association between caspase 9 polymorphisms and cancer risk from nine studies
      with 5,528 subjects for rs4645978, six studies with 2,403 subjects for rs105276
      and two studies for rs4645981. Overall meta-analysis indicated that no evidence
      of an association between rs4645978 and cancers was found. Through the stratified
      analysis, statistically significant reduced cancer risks were observed among
      Caucasians (AG vs AA: OR = 0.81, 95% CI = 0.66-0.99, P(heterogeneity) = 0.150 and
      the dominant model: OR = 0.86, 95% CI = 0.75-0.99, P(heterogeneity) = 0.290) and
      prostate cancer. As for rs105276, Ex5+32G>A polymorphism was found with
      protective effect in overall meta-analysis (AA vs GG: OR = 0.75, 95% CI = 0.60
      0.92, P(heterogeneity) = 0.887; A vs G: OR = 0.85, 95% CI = 0.77-0.95,
      P(heterogeneity) = 0.739 and the recessive model: OR = 0.68, 95% CI = 0.56-0.82,
      P(heterogeneity) = 0.309) and Asians group. While for rs4645981, a statistically
      significant increase in risk of lung cancer was shown in Asians (T vs C: OR =
      1.23, 95% CI = 1.07-1.42, P(heterogeneity) = 0.399 and the dominant model: OR =
      1.22, 95% CI = 1.04-1.43, P(heterogeneity) = 0.660). CONCLUSIONS/SIGNIFICANCE:
      Our meta-analysis suggests that the caspase 9 rs4645978 most likely contributes
      to decreased susceptibility to cancer in Caucasians and prostate cancer. The A
      allele of rs105276 might be a protective factor for cancer, especially for
      Asians. However, it seems that rs4645981 confers increased susceptibility to lung
      cancer in Asians.

PMID- 22616011
TI  - Mapping connectivity damage in the case of Phineas Gage.
AB  - White matter (WM) mapping of the human brain using neuroimaging techniques has
      gained considerable interest in the neuroscience community. Using diffusion
      weighted (DWI) and magnetic resonance imaging (MRI), WM fiber pathways between
      brain regions may be systematically assessed to make inferences concerning their
      role in normal brain function, influence on behavior, as well as concerning the
      consequences of network-level brain damage. In this paper, we investigate the
      detailed connectomics in a noted example of severe traumatic brain injury (TBI)
      which has proved important to and controversial in the history of neuroscience.
      We model the WM damage in the notable case of Phineas P. Gage, in whom a "tamping
      iron" was accidentally shot through his skull and brain, resulting in profound
      behavioral changes. The specific effects of this injury on Mr. Gage's WM
      connectivity have not previously been considered in detail. Using computed
      tomography (CT) image data of the Gage skull in conjunction with modern
      anatomical MRI and diffusion imaging data obtained in contemporary right handed
      male subjects (aged 25-36), we computationally simulate the passage of the iron
      through the skull on the basis of reported and observed skull fiducial landmarks
      and assess the extent of cortical gray matter (GM) and WM damage. Specifically,
      we find that while considerable damage was, indeed, localized to the left frontal
      cortex, the impact on measures of network connectedness between directly affected
      and other brain areas was profound, widespread, and a probable contributor to
      both the reported acute as well as long-term behavioral changes. Yet, while
      significantly affecting several likely network hubs, damage to Mr. Gage's WM
      network may not have been more severe than expected from that of a similarly
      sized "average" brain lesion. These results provide new insight into the
      remarkable brain injury experienced by this noteworthy patient.

PMID- 22616012
TI  - Alcohol-related context modulates performance of social drinkers in a visual
      Go/No-Go task: a preliminary assessment of event-related potentials.
AB  - BACKGROUND: Increased alcohol cue-reactivity and altered inhibitory processing
      have been reported in heavy social drinkers and alcohol-dependent patients, and
      are associated with relapse. In social drinkers, these two processes have been
      usually studied separately by recording event-related potentials (ERPs) during
      rapid picture presentation. The aim of our study was to confront social drinkers
      to a task triggering high alcohol cue-reactivity, to verify whether it
      specifically altered inhibitory performance, by using long-lasting background
      picture presentation. METHODS: ERP were recorded during visual Go/No-Go tasks
      performed by social drinkers, in which a frequent Go signal (letter "M"), and a
      rare No-Go signal (letter "W") were superimposed on three different types of
      background pictures: neutral (black background), alcohol-related and non alcohol
      related. RESULTS: Our data suggested that heavy social drinkers made more
      commission errors than light drinkers, but only in the alcohol-related context.
      Neurophysiologically, this was reflected by a delayed No-Go P3 component.
      CONCLUSIONS: Elevated alcohol cue-reactivity may lead to poorer inhibitory
      performance in heavy social drinkers, and may be considered as an important
      vulnerability factor in developing alcohol misuse. Prevention programs should be
      designed to decrease the high arousal of alcohol stimuli and strengthen cognitive
      control in young, at-risk individuals.

PMID- 22616013
TI  - Uptake rate of cationic mitochondrial inhibitor MKT-077 determines cellular
      oxygen consumption change in carcinoma cells.
AB  - OBJECTIVE: Since tumor radiation response is oxygen-dependent, radiosensitivity
      can be enhanced by increasing tumor oxygenation. Theoretically, inhibiting
      cellular oxygen consumption is the most efficient way to increase oxygen levels.
      The cationic, rhodacyanine dye-analog MKT-077 inhibits mitochondrial respiration
      and could be an effective metabolic inhibitor. However, the relationship between
      cellular MKT-077 uptake and metabolic inhibition is unknown. We hypothesized that
      rat and human mammary carcinoma cells would take up MKT-077, causing a decrease
      in oxygen metabolism related to drug uptake. METHODS: R3230Ac rat breast
      adenocarcinoma cells were exposed to MKT-077. Cellular MKT-077 concentration was
      quantified using spectroscopy, and oxygen consumption was measured using
      polarographic electrodes. MKT-077 uptake kinetics were modeled by accounting for
      uptake due to both the concentration and potential gradients across the plasma
      and mitochondrial membranes. These kinetic parameters were used to model the
      relationship between MKT-077 uptake and metabolic inhibition. MKT-077-induced
      changes in oxygen consumption were also characterized in MDA-MB231 human breast
      carcinoma cells. RESULTS: Cells took up MKT-077 with a time constant of ~1 hr,
      and modeling showed that over 90% of intracellular MKT-077 was bound or
      sequestered, likely by the mitochondria. The uptake resulted in a rapid decrease
      in oxygen consumption, with a time constant of ~30 minutes. Surprisingly the
      change in oxygen consumption was proportional to uptake rate, not cellular
      concentration. MKT-077 proved a potent metabolic inhibitor, with dose-dependent
      decreases of 45-73% (p = 0.003). CONCLUSIONS: MKT-077 caused an uptake rate
      dependent decrease in cellular metabolism, suggesting potential efficacy for
      increasing tumor oxygen levels and radiosensitivity in vivo.

PMID- 22616014
TI  - Kinship index variations among populations and thresholds for familial searching.
AB  - Current familial searching strategies are developed primarily based on autosomal
      STR loci, since most of the offender profiles in the forensic DNA databases do
      not contain Y-STR or mitochondrial DNA data. There are generally two familial
      searching methods, Identity-by-State (IBS) based methods or kinship index (KI)
      based methods. The KI based method is an analytically superior method because the
      allele frequency information is considered as opposed to solely allele counting.
      However, multiple KIs should be calculated if the unknown forensic profile may be
      attributed to multiple possible relevant populations. An important practical
      issue is the KI threshold to select for limiting the list of candidates from a
      search. There are generally three strategies of setting the KI threshold for
      familial searching: (1) SWGDAM recommendation 6; (2) minimum KI>=KI threshold;
      and (3) maximum KI>=KI threshold. These strategies were evaluated and compared by
      using both simulation data and empirical data. The minimum KI will tend to be
      closer to the KI appropriate for the population of which the forensic profile
      belongs. The minimum KI>=KI threshold performs better than the maximum KI>=KI
      threshold. The SWGDAM strategy may be too stringent for familial searching with
      large databases (e.g., 1 million or more profiles), because its KI thresholds
      depend on the database size and the KI thresholds of large databases have a
      higher probability to exclude true relatives than smaller databases. Minimum
      KI>=KI threshold strategy is a better option, as it provides the flexibility to
      adjust the KI threshold according to a pre-determined number of candidates or
      false positive/negative rates. Joint use of both IBS and KI does not
      significantly reduce the chance of including true relatives in a candidate list,
      but does provide a higher efficiency of familial searching.

PMID- 22616015
TI  - Bananas as an energy source during exercise: a metabolomics approach.
AB  - This study compared the acute effect of ingesting bananas (BAN) versus a 6%
      carbohydrate drink (CHO) on 75-km cycling performance and post-exercise
      inflammation, oxidative stress, and innate immune function using traditional and
      metabolomics-based profiling. Trained cyclists (N = 14) completed two 75-km
      cycling time trials (randomized, crossover) while ingesting BAN or CHO (0.2 g/kg
      carbohydrate every 15 min). Pre-, post-, and 1-h-post-exercise blood samples were
      analyzed for glucose, granulocyte (GR) and monocyte (MO) phagocytosis (PHAG) and
      oxidative burst activity, nine cytokines, F2-isoprostanes, ferric reducing
      ability of plasma (FRAP), and metabolic profiles using gas chromatography-mass
      spectrometry. Blood glucose levels and performance did not differ between BAN and
      CHO (2.41+/-0.22, 2.36+/-0.19 h, P = 0.258). F2-isoprostanes, FRAP, IL-10, IL-2,
      IL-6, IL-8, TNFalpha, GR-PHAG, and MO-PHAG increased with exercise, with no trial
      differences except for higher levels during BAN for IL-10, IL-8, and FRAP
      (interaction effects, P = 0.003, 0.004, and 0.012). Of 103 metabolites detected,
      56 had exercise time effects, and only one (dopamine) had a pattern of change
      that differed between BAN and CHO. Plots from the PLS-DA model visualized a
      distinct separation in global metabolic scores between time points [R2Y(cum) =
      0.869, Q2(cum) = 0.766]. Of the top 15 metabolites, five were related to liver
      glutathione production, eight to carbohydrate, lipid, and amino acid metabolism,
      and two were tricarboxylic acid cycle intermediates. BAN and CHO ingestion during
      75-km cycling resulted in similar performance, blood glucose, inflammation,
      oxidative stress, and innate immune levels. Aside from higher dopamine in BAN,
      shifts in metabolites following BAN and CHO 75-km cycling time trials indicated a
      similar pattern of heightened production of glutathione and utilization of fuel
      substrates in several pathways.

PMID- 22616016
TI  - In vivo analysis of the role of O-glycosylations of von Willebrand factor.
AB  - The objective of this project was to study the function of O-glycosylations in
      von Willebrand factor (VWF) life cycle. In total, 14 different murine Vwf cDNAs
      mutated on one or several O-glycosylations sites were generated: 9 individual
      mutants, 2 doublets, 2 clusters and 1 mutant with all 9 murine glycosylation
      sites mutated (Del-O-Gly). We expressed each mutated cDNA in VWF deficient-mice
      by hydrodynamic injection. An immunosorbent assay with Peanut Agglutinin (PNA)
      was used to verify the O-glycosylation status. Wild-type (WT) VWF expressed by
      hepatocytes after hydrodynamic injection was able to bind PNA with slightly
      higher affinity than endothelial-derived VWF. In contrast, the Del-O-Gly VWF
      mutant did not bind PNA, demonstrating removal of O-linked glycans. All mutants
      displayed a normal multimeric pattern. Two mutants, Del-O-Gly and T1255A/T1256A,
      led to expression levels 50% lower than those induced by WT VWF and their half
      life in vivo was significantly reduced. When testing the capacity of each mutant
      to correct the bleeding time of VWF-deficient mice, we found that S1486A, T1255A,
      T1256A and the doublet T1255A/T1256A were unable to do so. In conclusion we have
      shown that O-glycosylations are dispensable for normal VWF multimerization and
      biosynthesis. It also appears that some O-glycosylation sites, particularly the
      T1255 and T1256 residues, are involved in the maintenance of VWF plasma levels
      and are essential for normal haemostasis. As for the S1486 residue, it seems to
      be important for platelet binding as demonstrated in vitro using perfusion
      experiments.

PMID- 22616017
TI  - Modeling the control of trypanosomiasis using trypanocides or insecticide-treated
      livestock.
AB  - BACKGROUND: In Uganda, Rhodesian sleeping sickness, caused by Trypanosoma brucei
      rhodesiense, and animal trypanosomiasis caused by T. vivax and T. congolense, are
      being controlled by treating cattle with trypanocides and/or insecticides. We
      used a mathematical model to identify treatment coverages required to break
      transmission when host populations consisted of various proportions of wild and
      domestic mammals, and reptiles. METHODOLOGY/PRINCIPAL FINDINGS: An Ro model for
      trypanosomiasis was generalized to allow tsetse to feed off multiple host
      species. Assuming populations of cattle and humans only, pre-intervention Ro
      values for T. vivax, T. congolense, and T. brucei were 388, 64 and 3,
      respectively. Treating cattle with trypanocides reduced R(0) for T. brucei to <1
      if >65% of cattle were treated, vs 100% coverage necessary for T. vivax and T.
      congolense. The presence of wild mammalian hosts increased the coverage required
      and made control of T. vivax and T. congolense impossible. When tsetse fed only
      on cattle or humans, R(0) for T. brucei was <1 if 20% of cattle were treated with
      insecticide, compared to 55% for T. congolense. If wild mammalian hosts were also
      present, control of the two species was impossible if proportions of non-human
      bloodmeals from cattle were <40% or <70%, respectively. R(0) was <1 for T. vivax
      only when insecticide treatment led to reductions in the tsetse population. Under
      such circumstances R(0)<1 for T. brucei and T. congolense if cattle make up 30%
      and 55%, respectively of the non-human tsetse bloodmeals, as long as all cattle
      are treated with insecticide. CONCLUSIONS/SIGNIFICANCE: In settled areas of
      Uganda with few wild hosts, control of Rhodesian sleeping sickness is likely to
      be much more effectively controlled by treating cattle with insecticide than with
      trypanocides.

PMID- 22616018
TI  - In vitro and in vivo activity of a palladacycle complex on Leishmania
      (Leishmania) amazonensis.
AB  - BACKGROUND: Antitumor cyclopalladated complexes with low toxicity to laboratory
      animals have shown leishmanicidal effect. These findings stimulated us to test
      the leishmanicidal property of one palladacycle compound called DPPE 1.2 on
      Leishmania (Leishmania) amazonensis, an agent of simple and diffuse forms of
      cutaneous leishmaniasis in the Amazon region, Brazil. METHODOLOGY/PRINCIPAL
      FINDINGS: Promastigotes of L. (L.) amazonensis and infected bone marrow-derived
      macrophages were treated with different concentrations of DPPE 1.2. In in vivo
      assays foot lesions of L. (L.) amazonensis-infected BALB/c mice were injected
      subcutaneously with DPPE 1.2 and control animals received either Glucantime or
      PBS. The effect of DPPE 1.2 on cathepsin B activity of L. (L.) amazonensis
      amastigotes was assayed spectrofluorometrically by use of fluorogenic substrates.
      The main findings were: 1) axenic L. (L.) amazonensis promastigotes were
      destroyed by nanomolar concentrations of DPPE 1.2 (IC50 = 2.13 nM); 2)
      intracellular parasites were killed by DPPE 1.2 (IC50 = 128.35 nM), and the drug
      displayed 10-fold less toxicity to macrophages (CC50 = 1,267 nM); 3) one month
      after intralesional injection of DPPE 1.2 infected BALB/c mice showed a
      significant decrease of foot lesion size and a reduction of 97% of parasite
      burdens when compared to controls that received PBS; 4) DPPE 1.2 inhibited the
      cysteine protease activity of L. (L.) amazonensis amastigotes and more
      significantly the cathepsin B activity. CONCLUSIONS/SIGNIFICANCE: The present
      results demonstrated that DPPE 1.2 can destroy L. (L.) amazonensis in vitro and
      in vivo at concentrations that are non toxic to the host. We believe these
      findings support the potential use of DPPE 1.2 as an alternative choice for the
      chemotherapy of leishmaniasis.

PMID- 22616019
TI  - Characterisation of the native lipid moiety of Echinococcus granulosus antigen B.
AB  - Antigen B (EgAgB) is the most abundant and immunogenic antigen produced by the
      larval stage (metacestode) of Echinococcus granulosus. It is a lipoprotein, the
      structure and function of which have not been completely elucidated. EgAgB
      apolipoprotein components have been well characterised; they share homology with
      a group of hydrophobic ligand binding proteins (HLBPs) present exclusively in
      cestode organisms, and consist of different isoforms of 8-kDa proteins encoded by
      a polymorphic multigene family comprising five subfamilies (EgAgB1 to EgAgB5). In
      vitro studies have shown that EgAgB apolipoproteins are capable of binding fatty
      acids. However, the identity of the native lipid components of EgAgB remains
      unknown. The present work was aimed at characterising the lipid ligands bound to
      EgAgB in vivo. EgAgB was purified to homogeneity from hydatid cyst fluid and its
      lipid fraction was extracted using chloroform?methanol mixtures. This fraction
      constituted approximately 40-50% of EgAgB total mass. High-performance thin layer
      chromatography revealed that the native lipid moiety of EgAgB consists of a
      variety of neutral (mainly triacylglycerides, sterols and sterol esters) and
      polar (mainly phosphatidylcholine) lipids. Gas-liquid chromatography analysis
      showed that 16?0, 18?0 and 18?1(n-9) are the most abundant fatty acids in EgAgB.
      Furthermore, size exclusion chromatography coupled to light scattering
      demonstrated that EgAgB comprises a population of particles heterogeneous in
      size, with an average molecular mass of 229 kDa. Our results provide the first
      direct evidence of the nature of the hydrophobic ligands bound to EgAgB in vivo
      and indicate that the structure and composition of EgAgB lipoprotein particles
      are more complex than previously thought, resembling high density plasma
      lipoproteins. Results are discussed considering what is known on lipid metabolism
      in cestodes, and taken into account the Echinococcus spp. genomic information
      regarding both lipid metabolism and the EgAgB gene family.

PMID- 22616020
TI  - Dengue-1 envelope protein domain III along with PELC and CpG
      oligodeoxynucleotides synergistically enhances immune responses.
AB  - The major weaknesses of subunit vaccines are their low immunogenicity and poor
      efficacy. Adjuvants can help to overcome some of these inherent defects with
      subunit vaccines. Here, we evaluated the efficacy of the newly developed water-in
      oil-in-water multiphase emulsion system, termed PELC, in potentiating the
      protective capacity of dengue-1 envelope protein domain III. Unlike aluminum
      phosphate, dengue-1 envelope protein domain III formulated with PELC plus CpG
      oligodeoxynucleotides induced neutralizing antibodies against dengue-1 virus and
      increased the splenocyte secretion of IFN-gamma after in vitro re-stimulation.
      The induced antibodies contained both the IgG1 and IgG2a subclasses. A rapid
      anamnestic neutralizing antibody response against a live dengue virus challenge
      was elicited at week 26 after the first immunization. These results demonstrate
      that PELC plus CpG oligodeoxynucleotides broaden the dengue-1 envelope protein
      domain III-specific immune responses. PELC plus CpG oligodeoxynucleotides is a
      promising adjuvant for recombinant protein based vaccination against dengue
      virus.

PMID- 22616021
TI  - Lower richness of small wild mammal species and chagas disease risk.
AB  - A new epidemiological scenario involving the oral transmission of Chagas disease,
      mainly in the Amazon basin, requires innovative control measures. Geospatial
      analyses of the Trypanosoma cruzi transmission cycle in the wild mammals have
      been scarce. We applied interpolation and map algebra methods to evaluate
      mammalian fauna variables related to small wild mammals and the T. cruzi
      infection pattern in dogs to identify hotspot areas of transmission. We also
      evaluated the use of dogs as sentinels of epidemiological risk of Chagas disease.
      Dogs (n = 649) were examined by two parasitological and three distinct
      serological assays. kDNA amplification was performed in patent infections,
      although the infection was mainly sub-patent in dogs. The distribution of T.
      cruzi infection in dogs was not homogeneous, ranging from 11-89% in different
      localities. The interpolation method and map algebra were employed to test the
      associations between the lower richness in mammal species and the risk of
      exposure of dogs to T. cruzi infection. Geospatial analysis indicated that the
      reduction of the mammal fauna (richness and abundance) was associated with higher
      parasitemia in small wild mammals and higher exposure of dogs to infection. A
      Generalized Linear Model (GLM) demonstrated that species richness and positive
      hemocultures in wild mammals were associated with T. cruzi infection in dogs.
      Domestic canine infection rates differed significantly between areas with and
      without Chagas disease outbreaks (Chi-squared test). Geospatial analysis by
      interpolation and map algebra methods proved to be a powerful tool in the
      evaluation of areas of T. cruzi transmission. Dog infection was shown to not only
      be an efficient indicator of reduction of wild mammalian fauna richness but to
      also act as a signal for the presence of small wild mammals with high
      parasitemia. The lower richness of small mammal species is discussed as a risk
      factor for the re-emergence of Chagas disease.

PMID- 22616022
TI  - Detection, isolation and confirmation of Crimean-Congo hemorrhagic fever virus in
      human, ticks and animals in Ahmadabad, India, 2010-2011.
AB  - BACKGROUND: In January 2011, human cases with hemorrhagic manifestations in the
      hospital staff were reported from a tertiary care hospital in Ahmadabad, India.
      This paper reports a detailed epidemiological investigation of nosocomial
      outbreak from the affected area of Ahmadabad, Gujarat, India. PRINCIPAL FINDINGS:
      Samples from 3 suspected cases, 83 contacts, Hyalomma ticks and livestock were
      screened for Crimean-Congo hemorrhagic fever (CCHF) virus by qRT-PCR of which
      samples of two medical professionals (case C and E) and the husband of the index
      case (case D) were positive for CCHFV. The sensitivity and specificity of
      indigenous developed IgM ELISA to screen CCHFV specific antibodies in human serum
      was 75.0% and 97.5% respectively as compared to commercial kit. About 17.0%
      domestic animals from Kolat, Ahmadabad were positive for IgG antibodies while
      only two cattle and a goat showed positivity by qRT-PCR. Surprisingly, 43.0%
      domestic animals (Buffalo, cattle, sheep and goat) showed IgG antibodies in the
      adjoining village Jivanpara but only one of the buffalo was positive for CCHFV.
      The Hyalomma anatolicum anatolicum ticks were positive in PCR and virus
      isolation. CCHFV was isolated from the blood sample of case C, E in Vero E-6
      cells and Swiss albino mice. In partial nucleocapsid gene phylogeny from CCHFV
      positive human samples of the years 2010 and 2011, livestock and ticks showed
      this virus was similar to Tajikistan (strain TAJ/H08966), which belongs in the
      Asian/middle east genetic lineage IV. CONCLUSIONS: The likely source of CCHFV was
      identified as virus infected Hyalomma ticks and livestock at the rural village
      residence of the primary case (case A). In addition, retrospective sample
      analysis revealed the existence of CCHFV in Gujarat and Rajasthan states before
      this outbreak. An indigenous developed IgM ELISA kit will be of great use for
      screening this virus in India.

PMID- 22616023
TI  - Transcription factor OsHsfC1b regulates salt tolerance and development in Oryza
      sativa ssp. japonica.
AB  - BACKGROUND AND AIMS: Salt stress leads to attenuated growth and productivity in
      rice. Transcription factors like heat shock factors (HSFs) represent central
      regulators of stress adaptation. Heat shock factors of the classes A and B are
      well established as regulators of thermal and non-thermal stress responses in
      plants; however, the role of class C HSFs is unknown. Here we characterized the
      function of the OsHsfC1b (Os01g53220) transcription factor from rice.
      METHODOLOGY: We analysed the expression of OsHsfC1b in the rice japonica
      cultivars Dongjin and Nipponbare exposed to salt stress as well as after
      mannitol, abscisic acid (ABA) and H(2)O(2) treatment. For functional
      characterization of OsHsfC1b, we analysed the physiological response of a T-DNA
      insertion line (hsfc1b) and two artificial micro-RNA (amiRNA) knock-down lines to
      salt, mannitol and ABA treatment. In addition, we quantified the expression of
      small Heat Shock Protein (sHSP) genes and those related to signalling and ion
      homeostasis by quantitative real-time polymerase chain reaction in roots exposed
      to salt. The subcellular localization of OsHsfC1b protein fused to green
      fluorescent protein (GFP) was determined in Arabidopsis mesophyll cell
      protoplasts. PRINCIPAL RESULTS: Expression of OsHsfC1b was induced by salt,
      mannitol and ABA, but not by H(2)O(2). Impaired function of OsHsfC1b in the
      hsfc1b mutant and the amiRNA lines led to decreased salt and osmotic stress
      tolerance, increased sensitivity to ABA, and temporal misregulation of salt
      responsive genes involved in signalling and ion homeostasis. Furthermore, sHSP
      genes showed enhanced expression in knock-down plants under salt stress. We
      observed retarded growth of hsfc1b and knock-down lines in comparison with
      control plants under non-stress conditions. Transient expression of OsHsfC1b
      fused to GFP in protoplasts revealed nuclear localization of the transcription
      factor. CONCLUSIONS: OsHsfC1b plays a role in ABA-mediated salt stress tolerance
      in rice. Furthermore, OsHsfC1b is involved in the response to osmotic stress and
      is required for plant growth under non-stress conditions.

PMID- 22616024
TI  - Long-term population demography of Trillium recurvatum on loess bluffs in western
      Tennessee, USA.
AB  - BACKGROUND AND AIMS: Understanding the demography of long-lived clonal herbs,
      with their extreme modularity, requires knowledge of both their short- and long
      term survival and ramet growth patterns. The primary objective of this study was
      to understand the dynamics of a clonal forest herb, Trillium recurvatum, by
      examining temporal and small-scale demographic patterns. We hypothesized: (i)
      there would be more variability in the juvenile age class compared with non
      flowering adult and flowering adult classes due to year-to-year fluctuations in
      recruitment; (ii) rates of population growth (lambda) and increase (r) would be
      highest in non-flowering ramets due to a combination of transitions from the
      juvenile stage and reversions from flowering adults; and (iii) inter-ramet
      distances would be most variable between flowering and juvenile ramets due to a
      combination of clonal growth, seed dispersal by ants and ramet death over time.
      METHODOLOGY: Census data were collected on the total number of stems in the
      population from 1990 to 2007, and placed within one of three life stages
      (juvenile, three-leaf non-flowering and three-leaf flowering). Modified
      population viability equations were used to assess temporal population viability,
      and spatial structure was assessed using block krigging. Correlations were
      performed using current and prior season weather to current population
      demography. PRINCIPAL RESULTS: The first hypothesis was rejected. The second
      hypothesis was supported: population increase (r) and growth rate (lambda) were
      highest in non-flowering ramets. Finally, the third hypothesis was rejected:
      there was no apparent density dependence within this population of Trillium and
      no apparent spatial structure among life stages. CONCLUSIONS: Overall population
      density fluctuated over time, possibly due to storms that move soil, and prior
      year's temperature and precipitation. However, density remained at some dynamic
      stable level. The juvenile age class had greater variability for the duration of
      this study and population growth rate was greatest for non-flowering ramets.

PMID- 22616026
TI  - Comment on "Quality evaluation of microscopy and scanned histological images for
      diagnostic purposes": Are scanners better than microscopes?

PMID- 22616025
TI  - Epstein-Barr virus latent membrane protein 2A exacerbates experimental autoimmune
      encephalomyelitis and enhances antigen presentation function.
AB  - Multiple sclerosis (MS) is an inflammatory, autoimmune disease of the central
      nervous system. The cause of MS is still unknown but epidemiological and
      immunological studies have implicated Epstein-Barr virus (EBV), which infects B
      cells, as a possible etiological agent involved in disease. Of particular
      interest is EBV latent membrane protein 2A (LMP2A) because previous studies have
      demonstrated that LMP2A enhances the expansion and differentiation of B cells
      upon antigen stimulation, revealing a potential contribution of this protein in
      autoimmunity. Since B cells are thought to contribute to MS, we examined the role
      of LMP2A in the animal model experimental autoimmune encephalomyelitis (EAE). In
      this model, transgenic mice in which B cells express LMP2A show increased
      severity and incidence of disease. This difference was not due to lymphocyte
      recruitment into the CNS or differences in T cell activation, rather, we show
      that LMP2A enhances antigen presentation function.

PMID- 22616028
TI  - Changes, disruption and innovation: An investigation of the introduction of new
      health information technology in a microbiology laboratory.
AB  - BACKGROUND: It is expected that health information technology (HIT) will deliver
      a safer, more efficient and effective health care system. The aim of this study
      was to undertake a qualitative and video-ethnographic examination of the impact
      of information technologies on work processes in the reception area of a
      Microbiology Department, to ascertain what changed, how it changed and the impact
      of the change. MATERIALS AND METHODS: The setting for this study was the
      microbiology laboratory of a large tertiary hospital in Sydney. The study
      consisted of qualitative (interview and focus group) data and observation
      sessions for the period August 2005 to October 2006 along with video footage shot
      in three sessions covering the original system and the two stages of the Cerner
      implementation. Data analysis was assisted by NVivo software and process maps
      were produced from the video footage. RESULTS: There were two laboratory
      information systems observed in the video footage with computerized provider
      order entry introduced four months later. Process maps highlighted the large
      number of pre data entry steps with the original system whilst the newer system
      incorporated many of these steps in to the data entry stage. However, any time
      saved with the new system was offset by the requirement to complete some data
      entry of patient information not previously required. Other changes noted
      included the change of responsibilities for the reception staff and the physical
      changes required to accommodate the increased activity around the data entry
      area. CONCLUSIONS: Implementing a new HIT is always an exciting time for any
      environment but ensuring that the implementation goes smoothly and with minimal
      trouble requires the administrator and their team to plan well in advance for
      staff training, physical layout and possible staff resource reallocation.

PMID- 22616027
TI  - Handheld computing in pathology.
AB  - Handheld computing has had many applications in medicine, but relatively few in
      pathology. Most reported uses of handhelds in pathology have been limited to
      experimental endeavors in telemedicine or education. With recent advances in
      handheld hardware and software, along with concurrent advances in whole-slide
      imaging (WSI), new opportunities and challenges have presented themselves. This
      review addresses the current state of handheld hardware and software, provides a
      history of handheld devices in medicine focusing on pathology, and presents
      future use cases for such handhelds in pathology.

PMID- 22616029
TI  - Compressing pathology whole-slide images using a human and model observer
      evaluation.
AB  - INTRODUCTION: We aim to determine to what degree whole-slide images (WSI) can be
      compressed without impacting the ability of the pathologist to distinguish benign
      from malignant tissues. An underlying goal is to demonstrate the utility of a
      visual discrimination model (VDM) for predicting observer performance. MATERIALS
      AND METHODS: A total of 100 regions of interest (ROIs) from a breast biopsy whole
      slide images at five levels of JPEG 2000 compression (8:1, 16:1, 32:1, 64:1, and
      128:1) plus the uncompressed version were shown to six pathologists to determine
      benign versus malignant status. RESULTS: There was a significant decrease in
      performance as a function of compression ratio (F = 14.58, P < 0.0001). The
      visibility of compression artifacts in the test images was predicted using a VDM.
      Just-noticeable difference (JND) metrics were computed for each image, including
      the mean, median, >=90th percentiles, and maximum values. For comparison, PSNR
      (peak signal-to-noise ratio) and Structural Similarity (SSIM) were also computed.
      Image distortion metrics were computed as a function of compression ratio and
      averaged across test images. All of the JND metrics were found to be highly
      correlated and differed primarily in magnitude. Both PSNR and SSIM decreased with
      bit rate, correctly reflecting a loss of image fidelity with increasing
      compression. Observer performance as measured by the Receiver Operating
      Characteristic area under the curve (ROC Az) was nearly constant up to a
      compression ratio of 32:1, then decreased significantly for 64:1 and 128:1
      compression levels. The initial decline in Az occurred around a mean JND of 3,
      Minkowski JND of 4, and 99th percentile JND of 6.5. CONCLUSION: Whole-slide
      images may be compressible to relatively high levels before impacting WSI
      interpretation performance. The VDM metrics correlated well with artifact
      conspicuity and human performance.

PMID- 22616030
TI  - Investigation into diagnostic agreement using automated computer-assisted
      histopathology pattern recognition image analysis.
AB  - The extent to which histopathology pattern recognition image analysis (PRIA)
      agrees with microscopic assessment has not been established. Thus, a commercial
      PRIA platform was evaluated in two applications using whole-slide images.
      Substantial agreement, lacking significant constant or proportional errors,
      between PRIA and manual morphometric image segmentation was obtained for
      pulmonary metastatic cancer areas (Passing/Bablok regression). Bland-Altman
      analysis indicated heteroscedastic measurements and tendency toward increasing
      variance with increasing tumor burden, but no significant trend in mean bias. The
      average between-methods percent tumor content difference was -0.64. Analysis of
      between-methods measurement differences relative to the percent tumor magnitude
      revealed that method disagreement had an impact primarily in the smallest
      measurements (tumor burden <3%). Regression-based 95% limits of agreement
      indicated substantial agreement for method interchangeability. Repeated measures
      revealed concordance correlation of >0.988, indicating high reproducibility for
      both methods, yet PRIA reproducibility was superior (C.V.: PRIA = 7.4, manual =
      17.1). Evaluation of PRIA on morphologically complex teratomas led to diagnostic
      agreement with pathologist assessments of pluripotency on subsets of teratomas.
      Accommodation of the diversity of teratoma histologic features frequently
      resulted in detrimental trade-offs, increasing PRIA error elsewhere in images.
      PRIA error was nonrandom and influenced by variations in histomorphology. File
      size limitations encountered while training algorithms and consequences of
      spectral image processing dominance contributed to diagnostic inaccuracies
      experienced for some teratomas. PRIA appeared better suited for tissues with
      limited phenotypic diversity. Technical improvements may enhance diagnostic
      agreement, and consistent pathologist input will benefit further development and
      application of PRIA.

PMID- 22616031
TI  - Estrogen receptor testing and 10-year mortality from breast cancer: A model for
      determining testing strategy.
AB  - BACKGROUND: The use of adjuvant tamoxifen therapy in the treatment of estrogen
      receptor (ER) expressing breast carcinomas represents a major advance in
      personalized cancer treatment. Because there is no benefit (and indeed there is
      increased morbidity and mortality) associated with the use of tamoxifen therapy
      in ER-negative breast cancer, its use is restricted to women with ER expressing
      cancers. However, correctly classifying cancers as ER positive or negative has
      been challenging given the high reported false negative test rates for ER
      expression in surgical specimens. In this paper I model practice recommendations
      using published information from clinical trials to address the question of
      whether there is a false negative test rate above which it is more efficacious to
      forgo ER testing and instead treat all patients with tamoxifen regardless of ER
      test results. METHODS: I USED DATA FROM RANDOMIZED CLINICAL TRIALS TO MODEL TWO
      DIFFERENT HYPOTHETICAL TREATMENT STRATEGIES: (1) the current strategy of treating
      only ER positive women with tamoxifen and (2) an alternative strategy where all
      women are treated with tamoxifen regardless of ER test results. The variables
      used in the model are literature-derived survival rates of the different
      combinations of ER positivity and treatment with tamoxifen, varying true ER
      positivity rates and varying false negative ER testing rates. The outcome
      variable was hypothetical 10-year survival. RESULTS: The model predicted that
      there will be a range of true ER rates and false negative test rates above which
      it would be more efficacious to treat all women with breast cancer with tamoxifen
      and forgo ER testing. This situation occurred with high true positive ER rates
      and false negative ER test rates in the range of 20-30%. CONCLUSIONS: It is hoped
      that this model will provide an example of the potential importance of diagnostic
      error on clinical outcomes and furthermore will give an example of how the effect
      of that error could be modeled using real-world data from clinical trials.

PMID- 22616032
TI  - Computer-assisted imaging algorithms facilitate histomorphometric quantification
      of kidney damage in rodent renal failure models.
AB  - INTRODUCTION: Surgical 5/6 nephrectomy and adenine-induced kidney failure in rats
      are frequently used models of progressive renal failure. In both models, rats
      develop significant morphological changes in the kidneys and quantification of
      these changes can be used to measure the efficacy of prophylactic or therapeutic
      approaches. In this study, the Aperio Genie Pattern Recognition technology, along
      with the Positive Pixel Count, Nuclear and Rare Event algorithms were used to
      quantify histological changes in both rat renal failure models. METHODS: Analysis
      was performed on digitized slides of whole kidney sagittal sections stained with
      either hematoxylin and eosin or immunohistochemistry with an anti-nestin antibody
      to identify glomeruli, regenerating tubular epithelium, and tubulointerstitial
      myofibroblasts. An anti-polymorphonuclear neutrophil (PMN) antibody was also used
      to investigate neutrophil tissue infiltration. RESULTS: Image analysis allowed
      for rapid and accurate quantification of relevant histopathologic changes such as
      increased cellularity and expansion of glomeruli, renal tubular dilatation, and
      degeneration, tissue inflammation, and mineral aggregation. The algorithms
      provided reliable and consistent results in both control and experimental groups
      and presented a quantifiable degree of damage associated with each model.
      CONCLUSION: These algorithms represent useful tools for the uniform and
      reproducible characterization of common histomorphologic features of renal injury
      in rats.

PMID- 22616033
TI  - An unusual case of gallium scan mimicking a bone scan.
AB  - Gallium-67 localization is based on the fact that it binds to plasma proteins
      like transferrin and lactoferrin, which have iron-binding sites. Abnormal
      biodistribution of gallium-67 citrate can occur in iron-overload states. We
      report one such case of gallium scan mimicking a bone scan due to skeletal uptake
      of gallium.

PMID- 22616034
TI  - Agenesis of the gallbladder with the presence of a small dysmorphic cyst: role of
      magnetic resonance cholangiopancreatography.
AB  - We report a case of agenesis of the gallbladder with the presence of a small
      dysmorphic cyst, along the bed of the gallbladder and cystic duct. The patient
      presented to us with a suspected diagnosis of atrophic and sclerotic gallbladder
      that was not seen on ultrasound examination, indicating the need for
      cholecystectomy. The patient's medical history report mentioned agenesis of the
      left kidney. The existence of a congenital abnormality led us to suspect the
      inability to visualize the gallbladder was probably due to a possible agenesis of
      the gallbladder. The patient was investigated with magnetic resonance
      cholangiopancreatography (MRCP), that confirmed the suspected diagnosis and
      avoided unnecessary surgery. The hypothesis of anomalous development or agenesis
      of the gallbladder should always be suspected when the gallbladder is not visible
      on ultrasound imaging, especially in patients with other congenital anomalies. We
      believe that in all these patients, MRCP must always be performed to help make
      decisions on the treatment protocol.

PMID- 22616035
TI  - Report of Two Siblings with Overlapping Features of Ellis-van Creveld and Weyers
      Acrodental Dysostosis.
AB  - Skeletal dysplasias are a heterogenous group of disorders combining abnormalities
      in the skull and other skeletal bones. Weyers acrofacial dysostosis also known as
      Weyers acrodental dysostosis was first described in 1952, by Weyers, as a
      postaxial polydactyly, which had features distinct from, yet some in common with
      the Ellis-van Creveld Syndrome (EvC). Both the syndromes have been mapped to the
      same chromosome, 4p16. The cases reported here highlight the overlapping features
      of both syndromes, which are dissimilar in mode of inheritance and phenotypic
      severity, emphasizing the need for genetic analysis, to categorize these
      conditions.

PMID- 22616036
TI  - Rupture of plantaris muscle - a mimic: MRI findings.
AB  - Calf muscle trauma commonly involves the gastrocnemius and soleus muscles.
      Plantaris muscle is a vestigial muscle coursing through the calf. Similar
      clinical features may be seen with injury to the plantaris muscle. It can also
      mimic other conditions like deep vein thrombosis, rupture of Baker's cyst, and
      tumors. MRI is helpful in identifying and characterizing it. We report two cases
      of ruptured plantaris muscle seen on MRI.

PMID- 22616037
TI  - Idiopathic thrombus in the common carotid artery on digital subtraction
      angiography.
AB  - In the present study, we discuss the accuracy of digital subtraction angiography
      (DSA) in diagnosis of thrombus in the common carotid artery and its role in the
      medical management of this disorder. Between 2006 and 2011, four patients (age
      group ranging from 26 to 48 years) presented to our institution with symptoms of
      stroke. DSA in all these patients showed cigar-shaped filling defect in the
      common carotid artery. All the patients were managed successfully with
      anticoagulation treatment. Follow-up Duplex scan was done in all the patients.
      DSA is the gold standard to diagnose free floating thrombus in the common carotid
      artery. Medical management can be effective in these patients but a
      multidisciplinary team approach is needed for appropriate management.

PMID- 22616038
TI  - Review of metaplastic carcinoma of the breast: imaging findings and pathologic
      features.
AB  - Metaplastic carcinoma (MPC), an uncommon but often aggressive breast cancer, can
      be challenging to differentiate from other types of breast cancer and even benign
      lesions based on the imaging appearance. It has a variable pathology
      classification system. These types of tumors are generally rapidly growing
      palpable masses. MPCs on imaging can present with imaging features similar to
      invasive ductal carcinoma and probably even benign lesions. The purpose of this
      article is to review MPC of the breast including the pathology subtypes, imaging
      features, and imaging pathology correlations. By understanding the clinical
      picture, pathology, and overlap in imaging characteristics of MPC with invasive
      ductal carcinoma and probably benign lesions can assist in diagnosing these
      difficult malignancies.

PMID- 22616039
TI  - prenatal diagnosis of amniotic band syndrome in the third trimester of pregnancy
      using 3D ultrasound.
AB  - Amniotic band syndrome is characterized by a build-up of bands and strings of
      fibrous tissue that adhere to the fetus and can compress parts of the fetus, thus
      causing malformations and even limb amputation while the fetus is still in the
      uterus. The clinical manifestations are extremely variable and their extent may
      range from a single abnormality, like a constriction ring, to multiple
      abnormalities. Such abnormalities are generally diagnosed at the end of the first
      or the beginning of the second trimester using two-dimensional ultrasonography
      (2DUS). Three-dimensional ultrasonography (3DUS) in rendering mode allows spatial
      analysis of the fetus and amniotic band, thus enabling better comprehension of
      this pathological condition and better counseling for the parents. There has not
      previously been any evidence to show that 3DUS would be useful in cases of late
      diagnosis (third trimester) of amniotic band syndrome. In the present case, a
      primigravid woman underwent her second obstetric ultrasound scan in the 34(th)
      week, from which we observed two bands in contact with the right forearm, but
      with normal movement of this limb and its fingers. 3DUS made it possible to see
      the spatial relationship of these bands to the fetal body, thereby confirming
      their adherence to the limb. After the birth, the prenatal diagnosis of amniotic
      band syndrome without limb constriction was confirmed. A surgical procedure was
      carried out on the third day after birth to excise the bands, and the newborn was
      then discharged in a good general condition.

PMID- 22616040
TI  - Avoiding unnecessary fine-needle aspiration cytology by accuractely predicting
      the benign nature of thyroid nodules using ultrasound.
AB  - OBJECTIVE: The objective of this study was to describe a reliable ultrasound
      based index scoring system based on ultraound characteristics to identify benign
      thyroid nodules and avoid unnecessary fine needle aspiration cytology. MATERIALS
      AND METHODS: Patients undergoing ultrasound-guided fine-needle aspiration
      cytology (FNAC) for thyroid nodules were evaluated prospectively. A total of 284
      patients were evaluated from November 2005 to November 2011. There were 284
      nodules. Any solid or partly solid focal nodule in the thyroid gland was included
      in the study. Cysts with no solid component were excluded. We used LOGIQ 9 (GE
      Healthcare) scanner equipped with a 10--14 MHz linear matrix transducer with
      color and power Doppler capability. Four US characteristics were evaluated, i.e.,
      nodule margins, echo texture, vascularity, and calcification. Fine needle
      aspiration (FNA) was performed on all nodules. The nodules were labeled benign or
      suspicious using an ultrasound index score and the results compared with FNAC.
      Follicular neoplasms on fine-needle aspiration cytology were further assessed by
      excision biopsy and histology. Cytology/histology was used as the final
      diagnosis. RESULTS: In total 284 nodules were analyzed. All the 234 nodules in US
      labeled benign category were proven to be benign on cytology/histology. Therefore
      the specificity of ultrasound in labeling a nodule benign was 100%. Twenty of the
      50 nodules that were suspicious on US were malignant. The most significant US
      differentiating characteristics were nodule margins, vascularity, and
      microcalcification. CONCLUSION: Our results show that US can accurately
      characterize benign thyroid nodules using an index scoring system and therefore
      preclude FNAC in these patients.

PMID- 22616041
TI  - What happened to the large studies?

PMID- 22616042
TI  - Bending moments and types of failure of zirconia and titanium abutments with
      internal implant-abutment connections: a laboratory study.
AB  - PURPOSE: The aim of this study was to examine the bending moments and fracture
      patterns of different zirconia abutments with internal implant-abutment
      connections after static loading and to compare their bending moments to those of
      internally connected titanium abutments. MATERIALS AND METHODS: Three types of
      customized zirconia abutments (Straumann CARES abutments/Straumann BL implants
      [T1], Astra ZirDesign abutments/Astra Micro Thread OsseoSpeed implants [T2],
      Zirabut prototype abutments/Straumann SP implants [T3]) and one type of
      customized titanium abutment (control group, Straumann CARES abutments/Straumann
      BL implants [C]) were included. All abutments were one-piece abutments with an
      internal implant-abutment connection and were customized to the same shape but
      featured different implant-abutment connection designs. For each group, 20
      identical copies of a master abutment were fabricated and fixed on their
      corresponding implants. Half of the abutments in each group were left unrestored,
      and the other 10 received glass-ceramic crowns. Static loading was applied at a
      30-degree angle to the palatal surface until failure, and bending moments were
      calculated. The type of failure was characterized visually by dismounting the
      abutments and by examination of cross-sections of the embedded specimens. The
      results were analyzed statistically. RESULTS: The mean range of bending moments
      was higher for the unrestored groups (158.2 to 678.2 Ncm) than for the restored
      groups (117.9 to 419.4 Ncm). The highest mean bending moments were seen in the
      control group, both restored and unrestored (419.4/678.2 Ncm). Unrestored, T1 and
      T2 exhibited significantly higher bending moments than T3. This was also observed
      in the restored groups. CONCLUSION: Both the abutment material and the implant
      abutment connection design affected the bending moments of abutments after static
      loading. Internally connected zirconia abutments with horizontal mismatch to the
      implant exhibited significantly higher bending moments compared to those without
      horizontal mismatch.

PMID- 22616043
TI  - Load-dependent heat development, thermal effects, duration, and soft tissue
      preservation in piezosurgical implant site preparation: an experimental ex vivo
      study.
AB  - PURPOSE: Piezoelectric surgery is meant to be a gentle method for implant site
      preparation (ISP). However, the application of load and its influence on heat
      development over time and effects on soft tissue are unknown. Therefore, this
      study sought to evaluate heat development in the bone and the duration of the
      procedure according to load application, as well as preservation of the sinus
      floor mucosa during piezoelectric ISP. MATERIALS AND METHODS: One hundred twenty
      implant sites (6 mm deep x 3 mm wide) were prepared in the calvaria of ex vivo
      pig heads using piezoelectric surgery. The load applied to the working tip was
      increased in 100-g intervals up to 1,000 g. The bone temperature was measured,
      and thermal effects were analyzed histomorphometrically. The duration of each ISP
      was recorded. Another 12 ISPs were performed at the lateral wall of the maxillary
      sinus in the vicinity of the sinus floor mucosa, and sites were checked for
      perforation. RESULTS: Temperature and histologic effects of heat demonstrated a
      significant positive correlation with the applied load. The duration of ISP was
      significantly negatively correlated with load application. The maximum
      temperature generated by piezoelectric surgery was 64.5 degrees C (load of 901 to
      1,000 g). At a load of 401 to 500 g, the average temperature was 40.2 degrees C
      +/- 3.3 degrees C, the average thermal damage extended 115.9 +/- 16.3 MUm beyond
      the ISP area, and the maximum temperature did not exceed 47 degrees C. The
      average duration of ISP using this load interval was 45.5 +/- 9.4 seconds. Two
      perforations of the sinus floor mucosa were detected. CONCLUSIONS: In the present
      setting, the applied load during piezoelectric ISP should not exceed 500 g to
      prevent temperatures above 47 degrees C in the bony implant socket. With a load
      of 400 to 500 g, ISP took 40 to 50 seconds.

PMID- 22616044
TI  - A novel device for resonance frequency assessment of one-piece implants.
AB  - PURPOSE: Immediate loading and/or restoration of dental implants requires the
      assessment of implant stability, which is best performed by resonance frequency
      analysis (RFA) prior to loading. One-piece dental implants are usually used for
      immediate loading, but there is currently no available reliable method to assess
      the primary stability of one-piece dental implants. Therefore, this study sought
      to validate a novel device designed for RFA measurements of one-piece implants.
      MATERIAL AND METHODS: Thirty (3.75 x 13 mm) internal-hex implants (Seven, MIS)
      were divided into two groups; 15 were placed in an acrylic glass block and 15
      were placed in fresh porcine jawbone using 30 N/cm2 of insertion torque. Implant
      stability quotient (ISQ) values were measured using the Osstell Mentor device;
      then, a new external fixation device was attached to the implant abutment with a
      10-mm arm extending from the implant to an internal-hex ring at its proximal end.
      ISQ values were measured at the implant's internal hex and at the internal hex of
      the device, and the damping ratio was calculated. The measurements were repeated
      with 15 (3 x 13 mm) one-piece implants (UNO, MIS) attached to the same device.
      RESULTS: The damping ratio between the implant and the proximal device was 23.6%
      +/- 4% in acrylic glass (50.1 +/- 1.7 ISQ and 38.2 +/- 1.8 ISQ, respectively) and
      23.1% +/- 3% in porcine bone (74.9 +/- 2.8 ISQ and 57.5 +/- 0.5 ISQ,
      respectively). ISQ values determined by the device on one-piece and two-piece
      implants were similar (57.4 +/- 0.9 and 57.5 +/- 0.5, respectively). CONCLUSION:
      With the present validation of this external fixation device for the measurements
      of implant stability using RFA, it is now possible to measure primary stability
      of any one-piece implant system, obviating the need for custom-made Osstell
      adaptors.

PMID- 22616045
TI  - Influence of vertical misfit of titanium and zirconia frameworks on peri-implant
      strain.
AB  - PURPOSE: To assess the influence of misfit of implant titanium and zirconia
      frameworks on peri-implant strains. MATERIALS AND METHODS: Two Branemark implants
      were inserted in the areas of the mandibular left second premolar and second
      molar of an artificial epoxy resin mandible. From this model, five titanium and
      five zirconia frameworks of similar design were fabricated by means of computer
      numeric controlled milling. Strain gauges were mounted around each implant to
      assess strain development as a result of framework fit/misfit. In addition, the
      vertical gap at the framework-implant interface was measured using an optical
      microscope when only one screw was tightened (one-screw test) and when both
      screws were tightened (two-screw test). The vertical fit of the frameworks was
      altered by introducing one to three nominally 30-MUm steel shims on one of the
      implants. The data were analyzed statistically using one-way analysis of variance
      and the Mann-Whitney test. RESULTS: For each condition, a measurable amount of
      strain was recorded. As more vertical misfit was introduced, a linear increase in
      peri-implant strains was observed. The two framework materials generated similar
      amounts of strain. A direct relationship was observed between strain and the
      vertical gap. CONCLUSIONS: The magnitude of peri-implant strain is primarily
      affected by the fit of the framework rather than the material. Titanium and
      zirconia frameworks showed a similar outcome in relation to fit and strain
      development.

PMID- 22616046
TI  - Marginal accuracy of three implant-ceramic abutment configurations.
AB  - PURPOSE: Microgaps at the implant-abutment interface allow for microbial
      colonization, which can lead to peri-implant tissue inflammation. This study
      sought to determine the marginal accuracy of three different implant-zirconium
      oxide (zirconia) abutment configurations and one implant?titanium abutment
      configuration. MATERIALS AND METHODS: Three combinations of implants with custom
      made zirconia abutments were analyzed (n = 5/group): NobelProcera
      abutments/titanium inserts on Replace Select Tapered TiUnite implants (Nobel
      Biocare) (NP); Encode abutments/NanoTite Tapered Certain implants (Biomet 3i)
      (B3i); Astra Tech Dental Atlantis abutments/Biomet 3i NanoTite Tapered Certain
      implants (At). Five custom-made Encode titanium abutments/NanoTite Tapered
      Certain implants (Ti) were used as a control group. All abutments were fabricated
      with computer-aided design/computer-assisted manufacture. One-hundred twenty
      vertical gap measurements were made per sample using scanning electron microscopy
      (15 scans x 4 aspects of each specimen [buccal, mesial, palatal, distal] x 2
      measurements). Analysis of variance was used to compare the marginal fit values
      among the four groups, the specimens within each group, and the four aspects of
      each specimen. RESULTS: Mean (+/- standard deviation) gap values were 8.4 +/- 5.6
      MUm (NP), 5.7 +/- 1.9 MUm (B3i), 11.8 +/- 2.6 MUm (At), and 1.6 +/- 0.5 MUm (Ti).
      A significant difference was found between B3i and At. No difference resulted
      between NP with the other two groups. Gap values were significantly smaller for
      Ti relative to all zirconia systems. For each ceramic abutment configuration, the
      fit was significantly different among the five specimens. For 12 of the 15
      ceramic abutment specimens, gap values sorted by aspect were significantly
      different. CONCLUSIONS: The implant?titanium abutment connection showed
      significantly better fit than all implant?zirconia abutment configurations, which
      demonstrated mean gaps that were approximately three to seven times larger than
      those in the titanium abutment system.

PMID- 22616047
TI  - Comparison of the accuracy of plastic and metal stock trays for implant
      impressions.
AB  - PURPOSE: This in vitro study evaluated the dimensional accuracy of two impression
      techniques (tapered and splinted) with two stock trays (plastic and metal) for
      implant-supported prostheses. MATERIALS AND METHODS: A master cast with four
      parallel abutment analogs and a passive framework were fabricated. Polyvinyl
      siloxane impression material was used for all impressions with two metal stock
      trays and two plastic stock trays (closed and open trays). Four groups (tapered
      plastic, splinted plastic, tapered metal, and splinted metal) and a control group
      (master cast) were tested (n = 5 for each group). After the framework was seated
      on each of the casts, one abutment screw was tightened, and the marginal gap
      between the abutment and framework on the other side was measured with a
      stereomicroscope. The measurements were analyzed with the Kruskal-Wallis one-way
      analysis of variance on ranks test followed by the Dunn method. RESULTS: The mean
      values (+/- standard deviations) for the abutment/framework interface gaps were:
      master cast, 32 +/- 2 MUm; tapered metal, 44 +/- 10 MUm; splinted metal, 69 +/-
      28 MUm; tapered plastic, 164 +/- 58 MUm; splinted plastic, 128 +/- 47 MUm. No
      significant difference was detected between the master cast, tapered metal, and
      splinted metal groups or between the tapered and splinted plastic groups.
      CONCLUSIONS: In this study, the rigidity of the metal stock tray ensured better
      results than the plastic stock tray for implant impressions with a high-viscosity
      impression material (putty). Statistically similar results were obtained using
      tapered impression copings and splinted squared impression copings. The tapered
      impression copings technique and splinted squared impression copings technique
      with a metal stock tray produced precise casts with no statistically significant
      difference in interface gaps compared to the master cast.

PMID- 22616048
TI  - Leakage of saliva through the implant-abutment interface: in vitro evaluation of
      three different implant connections under unloaded and loaded conditions.
AB  - PURPOSE: Bacterial leakage along the implant-abutment interface, with consequent
      species harboring the inner parts of two-part dental implant systems, has been
      reported in the literature. The aim of this in vitro study was to evaluate
      bacterial leakage from human saliva to the internal part of the implants along
      the implant-abutment interface under loaded and unloaded conditions using DNA
      Checkerboard. MATERIALS AND METHODS: Sixty dental implants--20 each of external
      hexagon, internal-hexagon, and Morse cone-connection designs--and their conical
      abutments were used in this study. Each group was subdivided into two groups of
      10 loaded and 10 unloaded implants. The assemblies were immersed in human saliva
      and either (1) loaded with 500,000 cycles at 120 N (experimental group) or (2)
      incubated in static conditions for 7 days at 35 degrees C (unloaded control
      group). RESULTS: Microorganisms were found in the internal surfaces of all types
      of connections. The Morse cone connection presented the lowest count of
      microorganisms in both the unloaded and loaded groups. Loaded implants presented
      with higher counts of microorganisms than unloaded implants for external- and
      internal-hex connections. CONCLUSION: Bacterial species from human saliva may
      penetrate along the implant-abutment interface under both unloaded and loaded
      conditions for all connections evaluated. Morse cone-connection implants showed
      the lowest counts of microorganisms for both conditions. External- and internal
      hex implants showed a higher incidence of bacteria and higher bacterial counts
      after simulated loading.

PMID- 22616049
TI  - Assessment of osteointegrative response around dental implants using technetium
      99-methylene diphosphate scintigraphy: a comparison of two implant surfaces in a
      rabbit model.
AB  - PURPOSE: To compare the metabolic activity at the bone-implant interface of
      implants with machined and rough surfaces using bone scintigraphy during the in
      vivo process of osseointegration in a rabbit model, as well to establish a
      correlation between activity index (AI) and the bone-implant contact percentage
      (%BIC). MATERIALS AND METHODS: Twenty-four implants were placed (12 with a
      machined surface and 12 with a rough titanium oxide surface) in 12 New Zealand
      White rabbits. Preoperatively and during the postoperative period (at 15 days and
      at monthly intervals), animals underwent bone scintigraphy with technetium 99m
      methylene diphosphate (Tc-99m-MDP), and the AI for each implant was calculated by
      planar and pinhole collimator scintigraphy. A total of 240 AIs were obtained;
      after animal sacrifice at 105 days postsurgery, the %BIC was measured by scanning
      electron microscopy in 10 samples of each implant surface type. RESULTS: The
      activity-time curve showed a similar morphology for both implant types and both
      scintigraphy techniques. The maximum mean AI appeared after 15 days of
      implantation and was higher in machined implants. Significant differences were
      not found in the %BIC according to implant type. A significant correlation
      between the mean activity registered in the first postoperative scintigraph and
      the mean %BIC at the end of the study was observed for machined implants only.
      CONCLUSIONS: Tc-99m-MDP is useful for the assessment of osseous metabolic
      activity associated with different microsurfaces. The association between mean AI
      and %BIC was only demonstrated for machined implants in the first postoperative
      scintigraphy image.

PMID- 22616050
TI  - Effects of thermocycling on the retention of various cements of one-unit and
      three-unit fixed implant-supported restorations.
AB  - PURPOSE: To investigate the physical retention of different cements on one-unit
      and three-unit implant-supported restorations before and after thermocycling.
      MATERIALS AND METHODS: Twenty acrylic resin maxilla models with a single missing
      tooth and three missing teeth were fabricated and implants were placed. Cast
      partial denture copings were cemented to Straumann solid abutments with seven
      different cements. Specimens were placed in a humidifier at 37 degrees C for 24
      hours; half of them were then subjected to thermocycling. The tensile force was
      measured using a universal testing machine with a crosshead speed of 0.5 mm/min.
      The retention force required to remove the specimens was recorded and the data
      were submitted to statistical analyses. RESULTS: The retentive strength of the
      cements was highest for Multilink Implant, followed in descending order by
      Kavitan Cem, Adhesor Carbofine, Premier Implant, Adhesor, RelyX Temp, and Cavex
      before and after thermocycling for both one- and three-unit restorations. The
      bond strength was statistically significantly higher for three-unit than for one
      unit restorations before and after thermocycling, and there were statistically
      significant differences between cements for all groups before and after
      thermocycling. Both groups showed a statistically significant decrease in bond
      strength after thermocycling, and the largest differences were seen for Cavex and
      RelyX Temp for one-unit restorations and Cavex, RelyX Temp, and Kavitan Cem for
      three-unit restorations. CONCLUSIONS: The bond strength value was higher for
      three-unit than for one-unit restorations, and thermocycling reduced the bond
      strength of cements, especially Cavex, RelyX Temp, and Kavitan Cem.

PMID- 22616051
TI  - Changes in retention force with electroplated copings on conical crowns: a
      comparison of gold and zirconia primary crowns.
AB  - PURPOSE: The aim of this study was to examine the wear behavior of conical crowns
      with electroplated gold copings that are used to connect implants and teeth to a
      removable denture. Gold alloy and zirconium dioxide ceramic crowns were compared.
      MATERIALS AND METHODS: Fifteen crowns each were milled for two groups: gold alloy
      and zirconium dioxide. Each specimen had a 2-degree taper. The electroplated
      coping was established by direct electroforming. The retentive forces and the
      correlating distance during insertion and separation were measured after 10,000
      wear cycles were applied. The wear testing was separated into a start phase, an
      initial wear phase, and the long-term wear period. The retention force value and
      the force-distance integral of the first 0.3 mm of each cycle were calculated.
      RESULTS: The changes in retention force and integral did not differ significantly
      between both groups in the start and the initial wear phase. No differences were
      seen in force development during the long-term wear period. Only the force
      distance integral showed a significant difference: the median values of the gold
      crowns increased slightly, and they decreased slightly for the zirconia crowns.
      The median force values never fell below 6 N for gold and 4 N for zirconia.
      CONCLUSIONS: Within the limitations of this study, the tested conical crowns
      showed clinically acceptable retentive properties. As with other retentive
      elements for dentures, the specimens tested showed the greatest amount of change
      in retentive forces during the first 2,000 cycles. The development of retention
      force in both groups was not significantly different. However, the zirconia
      specimens showed reduced variability, which is preferable in clinical practice.

PMID- 22616052
TI  - Evaluation of guided bone regeneration with poly(lactic acid-co-glycolic acid-co
      epsilon-caprolactone) porous membrane in lateral bone defects of the canine
      mandible.
AB  - PURPOSE: The aim of this study was to qualitatively evaluate a poly(lactic acid
      co-glycolic acid-co-epsilon-caprolactone) (PLGC) membrane as a barrier for guided
      bone regeneration in the canine mandible and to compare it to a nonresorbable
      polytetrafluoroethylene (PTFE) membrane. MATERIALS AND METHODS: Two wedge-shaped
      bone defects were created bilaterally in the mandibles of 12 beagle dogs. The
      bone defects in the left mandible were divided into three groups and treated as
      follows: PLGC membrane alone, PLGC membrane plus autogenous cortical bone chips,
      and titanium-reinforced expanded PTFE (TR-PTFE) membrane. The bone defects in the
      right mandible of each animal were left without membranes as a control. Computed
      tomography (CT) was performed at 3 and 6 months postoperative to evaluate bone
      regeneration. After a healing period of 6 months, the mandibles were removed en
      bloc for micro-CT and histologic analyses. RESULTS: CT analyses at 3 and 6 months
      showed that there was significantly more bone augmentation at all experimental
      sites than at the control sites. The volume of bone at defect sites covered with
      TR-PTFE was significantly greater than at defect sites covered with PLGC membrane
      with or without autogenous cortical bone. Micro-CT measurements showed that the
      volume of new bone formed at sites covered with TR-PTFE was significantly greater
      than at sites covered with PLGC membrane. However, the density of new bone was
      significantly higher at sites covered with PLGC membrane, with or without
      cortical bone, than at sites covered with TR-PTFE. Histologic analysis verified
      the presence of well-vascularized loose connective tissue in the pores of the
      PLGC membrane. CONCLUSIONS: Compared to TR-PTFE, the macroporous bioresorbable
      PLGC membrane did not significantly increase the amount of new bone in defect
      sites, but it facilitated the regeneration of mature bone.

PMID- 22616054
TI  - Comparison of immediate and delayed implants in the maxillary molar region: a
      retrospective study of 123 implants.
AB  - PURPOSE: The purpose of this study was to compare marginal bone loss and success
      rates 1 year after implants had been placed in maxillary molar sites, either
      immediately postextraction or after the extraction sites had healed (delayed).
      MATERIALS AND METHODS: A retrospective case study was made of subjects treated
      with immediate or delayed dental implants in the maxillary molar region between
      January 2006 and December 2008. A protocol was prepared in which patient age,
      sex, implant length and diameter, type of prosthesis, buccal plate width, and use
      of bone grafting were recorded. After 12 months, data relating to the clinical
      and radiologic conditions of the implants and the success rate according to the
      criteria of Buser et al were recorded. The variables were analyzed statistically
      (Student t test, Pearson correlation, Games-Howell test). RESULTS: The study
      included 123 implants placed in 70 patients; 35 implants were immediate and 88
      were delayed. Two immediate and six delayed implants failed, resulting in success
      rates of 94.3% and 93.2%, respectively. Average marginal bone loss was 0.56 mm
      for immediate implants and 0.67 mm for delayed implants. CONCLUSIONS: The
      placement of immediate implants in maxillary molar sites achieved similar results
      to implants placed in healed sites in the same region after 12 months. No
      statistically significant differences were found between implant survival rates
      or average marginal bone loss.

PMID- 22616053
TI  - Incidental findings from a retrospective study of 318 cone beam computed
      tomography consultation reports.
AB  - PURPOSE: Cone beam computed tomography (CBCT) is a three-dimensional radiographic
      technique used in planning implant therapy to help clinicians determine the
      volume and dimension of bone available for implant placement, and CBCT images
      potentially depict coincident findings. MATERIALS AND METHODS: Three hundred
      eighteen patients received CBCT scans prior to receiving implants, which were
      interpreted by blinded board-certified oral and maxillofacial radiologists. All
      incidental findings were defined as non-tooth-related pathologies or
      abnormalities. These findings were categorized and analyzed using descriptive
      statistics. RESULTS: The patients ranged in age from 16 to 91 years (mean age for
      men, 64.73 +/- 15.05 years; for women, 62.47 +/- 15.83 years). Controlling for
      age, men were 2.13 times more likely to have sinus pathology than women. Patients
      over age 65 were 5.01 times more likely to demonstrate vascular pathology (eg,
      carotid artery calcification) than patients ages 41 to 65; the likelihood versus
      patients ages 16 to 40 was 13.39. Women were 2.63 times more likely to display
      brain pathology (eg, pineal or pituitary calcifications). Controlling for gender,
      patients ages 41 to 65 were 3.17 times more likely to exhibit condylar pathology
      (eg, degenerative changes) than patients ages 16 to 40. Similarly, patients above
      age 65 were 3.53 times more likely to show condylar pathology than patients ages
      16 to 40, and women were 1.61 times more likely to have condylar pathology than
      men. Versus patients ages 16 to 40, patients ages 41 to 65 were 17.69 times more
      likely to show signs of vertebral pathology (eg, degenerative disc changes) and
      patients over age 65 were 28.67 times more likely to display vertebral pathology.
      CONCLUSION: CBCT scans frequently reveal non-tooth-related pathologies and/or
      abnormalities in the head and neck region. Therefore, comprehensive review of the
      entire CBCT image set is necessary.

PMID- 22616055
TI  - Two-year evaluation of a variable-thread tapered implant in extraction sites with
      immediate temporization: a multicenter clinical trial.
AB  - PURPOSE: The purpose of this clinical trial was to evaluate the survival rate,
      bone remodeling, and soft tissue health surrounding variable-thread tapered
      implants placed in fresh extraction sites and loaded immediately. MATERIALS AND
      METHODS: Sixty implants were placed in 55 patients at six centers according to a
      predetermined protocol. All implants were placed in extraction sockets and were
      subjected to immediate temporization. Definitive prostheses were placed within
      the first year. Clinical and radiographic examinations were performed at implant
      placement and after 3, 6, 12, and 24 months. Assessments of implant stability,
      Papilla Index, plaque, peri-implant mucosa, and marginal bone levels were
      performed at the respective visits. RESULTS: Fifty-five patients were treated and
      were restored with 58 single crowns and 1 two-unit fixed partial prosthesis. The
      cumulative survival rate was 98.3% after 2 years. One implant failed prior to 3
      months. The mean marginal bone remodeling from implant insertion to 1 year was 
      0.22 +/- 1.30 mm (n = 41), followed by an average bone gain of 0.12 +/- 0.77 mm
      (n = 33) between 12 and 24 months. Mean marginal bone remodeling was -0.10 +/-
      1.38 mm (n = 35) from implant insertion to 2 years. Papilla size increased
      significantly over the 2-year study period. Patient assessments of function,
      esthetics, and self-esteem also showed significant improvement. CONCLUSION: The
      24-month results indicate that the variable-thread tapered implant can be used
      safely and effectively under demanding conditions as an immediate postextraction
      tooth replacement.

PMID- 22616056
TI  - Development of implant stability during early healing of immediately loaded
      implants.
AB  - PURPOSE: To monitor the development of stability of immediately loaded implants
      during early healing. MATERIALS AND METHODS: A total of 90 interforaminally
      placed implants with an alkali-treated surface were considered. The stability of
      each implant was examined at placement and 1, 2, 3, 4, 5, 6, 8, and 10 weeks
      after the surgery using resonance frequency analysis (RFA) and damping capacity
      measurement. The development of implant stability, focusing on the decrease in
      stability (as measured by implant stability quotient [ISQ]) and the interplay of
      primary (ISQ0) and secondary implant stability, was evaluated. The implants were
      divided into three groups based on primary stability: group L (ISQ0 < 68), group
      M (ISQ0 68 to72), and group H (ISQ0 > 72). Stability curves for each group were
      created and analyzed statistically. Implant stability measurement results gained
      with RFA and damping capacity were compared employing the Wilcoxon paired test,
      correlation coefficients, and regression analysis. The threshold for statistical
      significance was set at P < .05. RESULTS: The most pronounced decrease in ISQ
      values occurred 1 week after implant placement (mean decrease of 2.2 ISQ). During
      the 10-week experiment, mean ISQ rose by 5.5 in group L and by 1.3 in group M and
      dropped by 1.8 in group H (P < .001). The coefficient of determination R2 = 0.06
      showed a weak dependence of RFA on the damping capacity (P < .001). CONCLUSIONS:
      Implants with low primary stability showed a significant increase in stability
      during healing. In contrast, implants with high primary stability lost some
      stability over time.

PMID- 22616057
TI  - Immediately loaded mandibular fixed implant prostheses using the all-on-four
      protocol: a report of 183 consecutively treated patients with 1 year of function
      in definitive prostheses.
AB  - PURPOSE: The purpose of this study was to evaluate a specific protocol using four
      implants to support immediately loaded fixed prostheses to restore edentulous and
      partially edentulous mandibles and report on the outcome after 1 year of function
      with the definitive prostheses. MATERIALS AND METHODS: A retrospective study was
      conducted of all patients who were treated between June 2008 and December 2010
      with fixed prostheses that were loaded immediately after placement of implants.
      The provisional prostheses were later replaced with computer-aided
      design/computer-assisted manufacture titanium frames supporting acrylic resin and
      denture teeth in the definitive prosthesis. All patients were followed for a
      minimum of 12 months and were assessed for implant survival and prosthetic
      performance, with descriptive statistics utilized to demonstrate results.
      RESULTS: One hundred eighty-three consecutive patients received immediately
      loaded axial and tilted implants according to the defined protocol. One implant
      failed, resulting in a 99.86% implant success rate. There were two catastrophic
      prosthetic failures (fracture of the titanium framework), for a 98.9% prosthetic
      success rate. Three patients (1.6%) presented with fracture of a prosthetic
      mandibular incisor tooth. No prosthetic screw loosening or fractures were seen.
      Radiographic evaluation revealed no major bone loss around dental implants.
      CONCLUSIONS: Based on this retrospective study, the following conclusions can be
      drawn: (1) this technique appears to provide a highly predictable implant
      performance; (2) it is necessary to critically evaluate framework design,
      especially around the connectors for cantilever extensions around the most distal
      implants; and (3) minor complications related to acrylic resin tooth fracture may
      be anticipated during the early phases of prosthetic treatment.

PMID- 22616058
TI  - Application and success of two stereolithographic surgical guide systems for
      implant placement with immediate loading.
AB  - PURPOSE: Two different stereolithographic surgical guide systems, NobelGuide
      (Nobel Biocare) and SimPlant (Materialise), were compared clinically, and the
      survival rates of the planned immediately loaded dental implants with
      prefabricated provisional restorations were evaluated. MATERIALS AND METHODS:
      Patients were treated with implants using either the Materialise SimPlant system
      or the Nobel Biocare system. All implants were planned on cone beam computed
      tomography (CBCT) or CT-derived images. Mucosa-, bone-, or tooth-supported
      stereolithographic guides were produced using the two commercial systems. A
      provisional was placed immediately after implant insertion in all cases. RESULTS:
      Fourteen patients were enrolled. Seventy-five implants were placed (34 with
      Materialise, 41 with Nobel Biocare) using stereolithographic surgical guides. All
      but one implant were loaded immediately with prefabricated provisionals. In all
      cases, implants were in place for a minimum of 12 months. No complications
      related to associated anatomy occurred. One implant failed, leading to a combined
      cumulative survival rate of 98.7%. There were no other intraoperative or
      postoperative complications. Implants placed by bone-supported guides had
      increased patient symptoms of postoperative swelling and discomfort. All
      provisionals were successful. CONCLUSIONS: Both types of stereolithographic
      surgical templates were sufficiently accurate in transferring the planned implant
      positions to the surgical field, allowing the placement of prefabricated
      provisionals. These technologies are most beneficial in patients in whom the
      simultaneous placement of multiple implants in combination with complex
      restorations is planned.

PMID- 22616059
TI  - The survival of ultrashort locking-taper implants.
AB  - PURPOSE: To evaluate the performance of 5-mm-long implants. MATERIALS AND
      METHODS: A retrospective cohort study was conducted between January 2008 and
      December 2009. The sample was composed of patients who had received at least one
      5-mm-wide, hydroxyapatite-coated Bicon implant. The outcome variable was implant
      failure. Descriptive statistics and univariate and multivariate Cox proportional
      hazards regression models, adjusted for multiple implants in the same patient,
      were utilized to identify predictors of dental implant failure. RESULTS: Two
      hundred ninety-one subjects who received 410 locking-taper implants were followed
      for an average of 20 months. Of these, 211 were ultrashort implants (57 were 5 x
      5.0 mm and 154 were 5 x 6.0 mm) and 199 were short implants (5 x 8.0 mm). Three
      hundred twenty-two implants (93.4%) were restored with single crowns. There was a
      higher proportion of ultrashort single-tooth implants (94.6%) as compared to
      short single-tooth implants (92.2%). Nine implants failed, for a cumulative
      survival rate of 97.5%. Of the failed implants, five were ultrashort (all 5 x 6.0
      mm) and four were short. No failures were documented for 5- x 5.0-mm ultrashort
      implants. There was no statistically significant difference (P = .68) in the
      Kaplan-Meier survival rates of ultrashort implants (97.6%) and short implants
      (95.2%). After adjusting for other covariates in a multivariate model, implant
      length was not associated with implant failure (P = .49). CONCLUSIONS: The
      survival of ultrashort (5- and 6-mm) implants was comparable to that of short (8
      mm) implants.

PMID- 22616060
TI  - Accuracy of implant placement with a stereolithographic surgical template.
AB  - PURPOSE: The possible advantages of stereolithographic (SLA) surgical template
      use have not been adequately demonstrated, and studies of the accuracy of
      computer-aided implant placement are few. The purpose of this in vivo study was
      to evaluate the accuracy of a computer-designed (SLA) surgical guide by comparing
      the three-dimensional positions of planned and placed implants. MATERIALS AND
      METHODS: One hundred sixteen implants were inserted in partially and completely
      edentulous patients using multiple SLA templates. Preoperative and postoperative
      computed tomographic images were compared. Four deviation parameters--global,
      angular, depth, and lateral--were defined and calculated between the planned and
      actual implant positions and analyzed statistically. RESULTS: The mean global
      deviations between planned and actual implant positions at the coronal and apical
      ends were 1.47 mm and 1.83 mm, respectively; the mean angular deviation was 5.09
      degrees. There were significant linear correlations at the implant level between
      coronal and angular deviations and between coronal and apical deviations.
      CONCLUSIONS: The study highlighted deviations between the postoperative position
      and the preoperative plan at the coronal and apical portions of the implant, as
      well as in the angulation of the implant. Although the reported deviation values
      were extremely high, they do not appear to have resulted in important clinical
      complications. This suggests the necessity of always keeping a safety zone of at
      least 2 mm to avoid critical anatomical structures.

PMID- 22616061
TI  - The positions of implant heads in relation to the fixed dental prosthesis: a
      comparison of multiple zygomatic implants with standard implants for the
      reconstruction of the atrophic maxilla.
AB  - PURPOSE: The aim of this study was to investigate the positions of dental
      implants at the crestal level and the occlusal level of a fixed dental prosthesis
      (FDP) in severely and moderately resorbed maxillae. Restorations supported by
      multiple zygomatic implants were compared with restorations supported by standard
      implants. MATERIAL AND METHODS: Between 2004 and 2007, measurements were
      performed on FDPs and working casts. Two groups were investigated: (1) patients
      with severe atrophy and extensive resorption into basal bone treated with
      multiple zygomatic implants (Zyg) and (2) patients with moderate atrophy with
      standard implants only (Stand). The areas bounded by the FDP at the implant level
      (A(impl)) and at the occlusal level (A(prost)) were calculated, and A(prost) 
      A(impl) represented the total horizontal overjet of the FDP. A(prost)/A(impl) was
      established as the degree of overlapping of these two areas. The transverse and
      sagittal dimensions at the implant level (T(impl) and S(impl)) and at the
      occlusal level (T(prost) and S(prost)) were also measured. T(impl)/S(impl) and
      T(prost)/S(prost) represented the shape of the superstructure at these respective
      levels. RESULTS: Seven consecutive patients in the Zyg group were matched by age
      and gender with seven individuals in the Stand group. In the Zyg group, 28
      zygomatic and 5 standard implants were placed; in the Stand group, 41 standard
      implants were placed, of which 3 were lost. All patients received an FDP. T(impl)
      was shorter and S(impl) was longer in the Zyg group, yielding a smaller
      T(impl)/S(impl) in this group. The Zyg group also displayed less overjet and a
      smaller A(prost)/A(impl) compared to the Stand group. CONCLUSION: Multiple
      zygomatic implants emerged through the residual crest with a more even
      distribution in the sagittal plane compared to standard implants and with a
      better congruence with the occlusal location of the FDP.

PMID- 22616062
TI  - Expression of interleukin 6 and tumor necrosis factor alpha in soft tissue over
      ceramic and metal implant materials before uncovering: a clinical pilot study.
AB  - PURPOSE: To compare the effect of ceramic and metal implant materials on the
      expression pattern of inflammatory cytokines in peri-implant soft tissue.
      MATERIALS AND METHODS: This split-mouth study included patients who received
      dental implants. In each patient, four different materials were used for the
      implant cover screws: the ceramic material titanium niobium oxynitride
      ([Ti,Nb]ON) with plasma-chemical oxidation treatment, (Ti,Nb)ON, a titanium
      tantalum alloy, and tantalum. Biopsy specimens of peri-implant tissue were
      harvested at reentry, 4 months after the initial surgery. Immunohistochemical
      staining was performed for tumor necrosis factor alpha (TNF-alpha) and
      interleukin 6 (IL-6). RESULTS: Six patients received a total of 24 dental
      implants with the four different types of implant cover screws. Quantitative
      analysis of TNF-alpha; and IL-6 expression showed the lowest expression of IL-6
      (1.5; interquartile range, 0 to 8.5) and TNF-alpha (4.8; interquartile range, 3.5
      to 7.5) in tissue adjacent to the (Ti,Nb)ON layer. In comparison to the metal
      surfaces, the expression of both cytokines was significantly lower (P = .01 and P
      = .03). CONCLUSIONS: The lowest levels of cytokine expression were observed in
      tissue adjacent to the ceramic (Ti,Nb)ON coating with plasma-chemical oxidation.
      Based on the results of this study, this ceramic layer shows promise as a
      biocompatible material, and further study is warranted.

PMID- 22616063
TI  - Intracoronal mandibular Kennedy Class I implant-tooth supported removable partial
      overdenture: a 2-year multicenter prospective study.
AB  - PURPOSE: The aim of this study was to assess the clinical status and radiographic
      and densitometric peri-implant tissue changes as parameters for the success or
      failure of 40 mandibular implants supporting intracoronal mandibular Kennedy
      Class I removable partial overdentures in a 2-year prospective study. MATERIALS
      AND METHODS: Twenty consecutively treated men who received mandibular implants
      bilaterally to support an intracoronal Kennedy Class I removable partial
      overdenture were selected. Plaque and gingival bleeding indices, probing pocket
      depths, marginal bone loss, and bone mineral density were recorded. Bone loss and
      density were assessed through intraoral periapical radiographs and dual-energy x
      ray absorptiometry, respectively. Data were recorded at the time of overdenture
      insertion and 6, 12, 18, and 24 months later. RESULTS: Two implants failed,
      resulting in a success rate of 95% after 24 months. The plaque and gingival
      bleeding indices changed significantly between the different observational
      periods. Within the physiologic limit, there were detrimental effects on both
      marginal bone levels and probing pocket depths. Meanwhile, the bone mineral
      density around the implants increased significantly in a time-dependent manner.
      CONCLUSION: Within the limitations of this study, mandibular implants supporting
      an intracoronal Kennedy Class I removable partial overdenture can be recommended
      as a viable treatment modality for rehabilitation of patients with partial
      bilateral mandibular posterior edentulism.

PMID- 22616064
TI  - Association between microbial flora and tissue abnormality around dental implants
      penetrating the skin in reconstructed oral cancer patients.
AB  - PURPOSE: Patients with skin-penetrating implants sometimes report episodic soft
      tissue reactions. This pilot clinical trial identified the oral microflora of the
      peri-implant sulcus of cancer patients with jaw reconstruction and compared sites
      with and without clinical signs of inflammation. MATERIALS AND METHODS: Ten
      patients were selected during routine follow-up of their implant-supported
      removable prostheses. Eligible patients had at least two intraoral skin
      penetrating implants; one showed clinical signs of inflammation with/without
      symptoms and the other served as a healthy control site. Eight of the 10 patients
      had undergone osseocutaneous fibula free flap reconstruction and two had received
      split-thickness skin grafts on the surface of the native mandible. Subjects were
      assessed on two visits, 30 to 40 days apart. Subgingival microbial samples were
      obtained and periodontal pocket depths were measured at the test implant
      abutment. Between visits, patients followed a strict oral hygiene regimen.
      Radiographic marginal bone loss around implants was measured using cone beam
      imaging during the second visit. The microflora were identified after isolation
      and purification of all growing colonies. RESULTS: The number of different
      microorganisms ranged from 10 to 21 per site. Among all patients, a total of 47
      different microorganisms were identified, but none were considered virulent red
      complex periodontal pathogens. By the time of the second visit, after adherence
      to strict mechanical oral hygiene, the average number of microorganisms per site
      was reduced through elimination of some species. Almost all subjects had
      identical microbial species in both sites, but the number of visible colonies was
      lower at the healthy site. CONCLUSION: Oral peri-implant epidermal proliferation
      does not appear to be caused by specific microbial pathogens but is likely
      related to increased microbial load in the implant sulci. Mechanical oral hygiene
      improves and maintains healthier peri-implant skin tissues.

PMID- 22616066
TI  - Digitally designed surgical guides for placing extraoral implants in the mastoid
      area.
AB  - PURPOSE: When planning implant therapy, knowledge of the bone volume in the
      implant area is needed to plan and place implants in the most appropriate
      locations from the prosthetic and surgical perspectives. Commercial software for
      digital planning of implants in the craniofacial region is not yet available.
      This article describes a method that enables digital planning of extraoral
      implants in the mastoid region utilizing commercially available computer-aided
      design (CAD) software and rapid-prototyping techniques to manufacture a
      corresponding surgical guide. MATERIALS AND METHODS: With the aid of CAD software
      designed for reverse engineering and three-dimensional animation, digital implant
      planning based on cone beam computed tomography (CBCT) scanning was performed. On
      the basis of this planning, surgical guides were digitally designed to facilitate
      the placement of dental implants in the mastoid area. The guides were fabricated
      using rapid prototyping. The appropriateness of the digitally designed surgical
      guides for placing extraoral implants was tested on six human cadaver heads with
      simulated bilateral ear defects. After implant placement, a second CBCT scan was
      performed to compare preoperative planning with the actual postoperative implant
      positions. RESULTS: Twenty-four implants were placed. The surgical guide helped
      the surgeon to place the implants at the preoperatively planned positions.
      Comparison of the CBCT scans revealed that adequate accuracy of implant placement
      was achieved, both for deviation of the neck (1.56 +/- 0.56 mm) and the tip (1.40
      +/- 0.53 mm) of the implant, and for deviation of the angulation of the implant
      (0.97 +/- 2.33 deg). CONCLUSION: The presented method for digitally planning
      extraoral implants in the mastoid area and designing surgical guides allows for
      placement of implants in the mastoid area in close proximity to the
      preoperatively planned implant position. The actual implant positions were
      satisfactory both surgically and prosthetically.

PMID- 22616065
TI  - Assessment of rehabilitation in edentulous patients treated with an immediately
      loaded complete fixed mandibular prosthesis supported by three implants.
AB  - PURPOSE: Conventionally, in patients with completely edentulous mandibles, fixed
      prostheses have been supported by four or more implants. However, an alternative
      protocol employing three implants and immediate loading has been developed. The
      objective of the present study was to assess the rehabilitation of edentulous
      patients treated with a complete fixed mandibular prosthesis with immediate
      loading and supported by three implants. MATERIALS AND METHODS: In this
      observational study, a total of 99 implants placed in 33 patients was evaluated
      after 18 months in use. Panoramic radiographs were digitized to measure bone loss
      at the mesial and distal surfaces of each implant. RESULTS: Mean peri-implant
      bone loss was 0.66 +/- 0.51 mm for the left implant, 0.92 +/- 0.61 mm for the
      central implant, and 0.82 +/- 0.53 mm for the right implant. The bone loss
      observed around the distal implants was similar to that seen around the central
      implant, and there were no statistically significant differences in peri-implant
      bone loss between the three implant locations. There was no significant
      correlation between implant length and bone loss. The results were compatible
      with the peri-implant bone loss that has been described for prostheses of the
      same type supported by larger numbers of implants. CONCLUSIONS: The use of a
      complete fixed mandibular prosthesis with immediate loading supported by three
      implants proved to be an adequate option for the rehabilitation of edentulous
      patients. The protocol allowed simplification of treatment while maintaining
      similar bone loss to that reported for the same type of treatment supported by a
      larger number of implants.

PMID- 22616067
TI  - Influence of crown-to-implant ratio, retention system, restorative material, and
      occlusal loading on stress concentrations in single short implants.
AB  - PURPOSE: The aim of this study was to assess the contributions of some prosthetic
      parameters such as crown-to-implant (C/I) ratio, retention system, restorative
      material, and occlusal loading on stress concentrations within a single posterior
      crown supported by a short implant. MATERIALS AND METHODS: Computer-aided design
      software was used to create 32 finite element models of an atrophic posterior
      partially edentulous mandible with a single external-hexagon implant (5 mm wide x
      7 mm long) in the first molar region. Finite element analysis software with a
      convergence analysis of 5% to mesh refinement was used to evaluate the effects of
      C/I ratio (1:1; 1.5:1; 2:1, or 2.5:1), prosthetic retention system (cemented or
      screwed), and restorative material (metal-ceramic or all ceramic). The crowns
      were loaded with simulated normal or traumatic occlusal forces. The maximum
      principal stress (stressmax) for cortical and cancellous bone and von Mises
      stress (stressvM) for the implant and abutment screw were computed and analyzed.
      The percent contribution of each variable to the stress concentration was
      calculated from the sum of squares analysis. RESULTS: Traumatic occlusion and a
      high C/I ratio increased stress concentrations. The C/I ratio was responsible for
      11.45% of the total stress in the cortical bone, whereas occlusal loading
      contributed 70.92% to the total stress in the implant. The retention system
      contributed 0.91% of the total stress in the cortical bone. The restorative
      material was responsible for only 0.09% of the total stress in the cancellous
      bone. CONCLUSION: Occlusal loading was the most important stress concentration
      factor in the finite element model of a single posterior crown supported by a
      short implant.

PMID- 22616068
TI  - The effect of prosthesis length and implant diameter on the stress distribution
      in tooth-implant-supported prostheses: a finite element analysis.
AB  - PURPOSE: The goal of this study was to compare the stress distribution of tooth
      implant-supported prostheses (TISPs) and solely implant-supported prostheses
      (ISPs) with two different pontic spans (three units versus four units). MATERIALS
      AND METHODS: Two-dimensional finite element models were constructed from the
      radiographs of polyester resin casts to mimic TISPs and ISPs. In all, eight
      models were analyzed. Occlusal loads of 15 N and 30 N were applied to the
      premolars and molars, respectively. The lateral and inferior borders of the
      models were constrained, with all degrees of freedom equal to zero. Eight-node
      elements with plane strain assumption were used for simulation. RESULTS: The
      authors found that TISPs with a short span and wider-diameter implants resulted
      in more homogenous stress distribution and less stress concentration on the
      implants. The long span yielded higher stress concentrations on the implants and
      between the pontics. CONCLUSIONS: In all models analyzed, stress concentrations
      were present in the implants.

PMID- 22616069
TI  - Stress distribution on scalloped implants with different microthread and
      connection configurations using three-dimensional finite element analysis.
AB  - PURPOSE: The objective of this study was to investigate the effects of different
      microthread designs and implant-abutment connection configurations of scalloped
      implants on stress distribution in bone using three-dimensional finite element
      analysis. MATERIALS AND METHODS: Three different designs of scalloped implants
      (two different microthread designs and one without microthreads) with two
      different connection systems and two flat-top implants with similar connection
      systems were compared in a bone model that mimicked the anterior maxilla.
      Vertical and oblique (30-degree) loading with 100 N of force was applied to eight
      models. Peak stress levels and the distribution of stress were observed. RESULTS:
      The stress pattern of scalloped implants was distinctively different from that
      observed on flat-top implants. Scalloped implants showed peak stresses in the
      proximal cortical bone as well as in the buccal and palatal cortical bone,
      whereas flat-top implants showed peak stresses mainly in the buccal and palatal
      cortical bone and limited stress in the proximal bone. The scalloped implant
      without microthreads and a conical platform-switched connection demonstrated the
      lowest peak stress levels. The scalloped implant with a straight platform
      connection generally showed peak stress that was two to three times higher than
      that seen in the conical platform-switched model. CONCLUSIONS: Peak stress levels
      in scalloped implants varied with microthread designs, connection configurations,
      and the direction of loading. The conical platform-switched connection seemed
      more important for a scalloped implant than the microthread design in reducing
      loading stresses exerted on the surrounding bone. Scalloped implants without
      microthread and a with a conical platform-switched connection or closed
      microthreads and a conical platform-switched connection showed consistently lower
      buccal bone stress than the flat-top implants in areas where the bone had a
      sloping and scalloping shape.

PMID- 22616070
TI  - This and that !

PMID- 22616071
TI  - Gene therapy and nasopharyngeal carcinoma.
AB  - In 2003, a non-replicating adenoviral gene therapy product received the world's
      first government licence for the treatment of head and neck cancer. Two years
      later approval was granted to a replication-selective adenovirus for the
      treatment of nasopharyngeal carcinoma in combination with chemotherapy. This
      review introduces the reader to gene therapy as an emerging treatment modality,
      and outlines its application to the management of nasopharyngeal carcinoma by
      examining recent pre-clinical and clinical research.

PMID- 22616072
TI  - Allergic rhinitis and associated factors in schoolchildren from Bogota, Colombia.
AB  - BACKGROUND: Allergic rhinitis is one of the most frequent chronic diseases among
      children. The objective of the study was to assess the prevalence of and the
      factors associated with self-reported allergic rhinitis symptoms in
      schoolchildren from Bogota, Colombia. METHODOLOGY/PRINCIPAL: We followed the
      International Study of Asthma and Allergies in Childhood (ISAAC) methodology. Our
      sample included 3,256 children aged 6 - 7 and 3,830 adolescents aged 13 - 14
      years. RESULTS: The prevalence of self-reported allergic rhinitis symptoms was
      30.8% among children and 36.6% among adolescents. Factors associated with self
      reported allergic rhinitis among children included current asthma and atopic
      dermatitis symptoms; use of acetaminophen in the first year of life and in the
      last 12 months; antibiotic use in the first year of life; high- school and
      university maternal education; smokers at home; and caesarean delivery. Among
      adolescents, associated factors included current asthma and atopic dermatitis
      symptoms; current acetaminophen use once per month; frequent fast-food
      consumption; cat exposure at home; and smoking. CONCLUSION: Further exploration
      of factors associated with allergic rhinitis symptoms is needed.

PMID- 22616073
TI  - Prevalence of chronic rhinosinusitis in Sao Paulo.
AB  - INTRODUCTION: Studies designed to investigate chronic rhinosinusitis (CRS)
      epidemiology play an important role to assess population's distribution and risk
      factors to result in the development and promotion of public health policies.
      METHOD: This study design is a survey carried out with a complex two-stage
      cluster sampling plan. Personal interviews were carried out with 2,003
      individuals. The questionnaire included the epidemiological criteria for CRS.
      Demographic data, history of physician-diagnosed respiratory diseases (asthma,
      sinusitis, rhinitis), smoking, family income, educational attainment, and
      household characteristics were also evaluated. RESULTS: The overall response rate
      was 93.9% of the households. Mean age was 39.8 +- 21 years; 45.33% were male. The
      overall prevalence of CRS in the city of Sao Paulo was 5.51%. We found a
      significant association between diagnosis of CRS and diagnosis of asthma and CRS
      and diagnosis of rhinitis and a significant association between presence of CRS
      and belonging to the low-income subgroup. CONCLUSION: The municipality of Sao
      Paulo has an urban population of 11 million. According to the present study, the
      prevalence of CRS is 5.51%, which represents more than 500,000 individuals
      affected by this condition in the city.

PMID- 22616074
TI  - A prospective study of bacterial flora in nasal cavity of patients with
      persistent allergic rhinitis.
AB  - It remains unanswered whether persistent allergic inflammation in nasal mucosa
      alters bacterial colonization and infection. The aim of this study was to
      investigate the bacterial flora in the nasal cavity of patients with persistent
      allergic rhinitis (PAR) and to correlate the bacteriological findings with
      presence of nasal symptoms, nasal eosinophil and neutrophil counts. A total of
      255 subjects, aged between 6 - 74 years (mean 33.9 years) was randomly selected
      from a population-based rhinitis survey study in Singapore. All subjects went
      through a thorough medical history and nasal examinations. Serum specific IgE to
      a panel of common house dust mites, nasal cytological and microbiological
      examinations were performed. PAR was diagnosed in 107 patients and none of them
      had received previous regular therapy. There is a significant relationship
      between PAR and eosinophil grades, but not with neutrophil count. No
      statistically significant difference was found in quantitative and qualitative
      bacterial flora in nasal cavity between PAR patients and subjects with non
      rhinitis or with non-allergic rhinitis. There is a significant inverse
      correlation between ongoing rhinorrhoea and quantitative bacterial load, and
      between signs of nasal mucosa (pale and edema) and the presence and type of
      bacterial pathogens. In conclusion, our study demonstrates that patients with
      untreated (or using PRN medicine) PAR do not result in a significant change in
      bacterial flora in their nasal cavity.

PMID- 22616075
TI  - Lysozyme expression is increased in the sinus mucosa of patients with chronic
      rhinosinusitis.
AB  - BACKGROUND: The presence of fungi and bacteria in the paranasal sinuses may
      contribute to ongoing inflammation. Lysozyme is an innate immune peptide with
      bactericidal and fungicidal activity. The expression of lysozyme in chronic
      rhinosinusitis (CRS) is poorly understood and deficiencies in lysozyme expression
      may contribute to the ongoing inflammation in CRS patients. OBJECTIVE: Determine
      lysozyme expression in sinus mucosa of normal and CRS patients with (CRSwNP) and
      without (CRSsNP) nasal polyps. METHODOLOGY: Sinus mucosa specimens (n = 82) were
      processed for standard histology, immunohistochemical localisation of lysozyme,
      immunofluorescent localisation of fungi, and qPCR analysis of lysozyme
      expression. RESULTS: CRS specimens displayed high-levels of lysozyme
      immunoreactivity in many of the abundant serous cells. Moderate levels were
      detected in some epithelial cells and inflammatory cells. Low levels were
      detected in some subepithelial glands of control specimens. No difference in
      immunoreactivity was detected between CRSwNP and CRSsNP specimens. Fungal
      elements were not visualised in any sinus specimen. qPCR analysis demonstrated
      variable lysozyme expression between individuals. CONCLUSIONS: Lysozyme protein
      expression is increased in patients with CRS, suggesting a defect in lysozyme
      expression is not responsible for the microbial colonisation often associated
      with CRS. The functional activity of lysozyme in CRS patients needs to be further
      investigated.

PMID- 22616076
TI  - Numerical simulation of humidification and heating during inspiration within an
      adult nose.
AB  - BACKGROUND: The temperature of inhaled air is highly relevant for the
      humidification process. Narrow anatomical conditions limit possibilities for in
      vivo measurements. Numerical simulations offer a great potential to examine the
      function of the human nose. OBJECTIVE: In the present study, the nasal
      humidification of inhaled air was simulated simultaneously with temperature
      distribution during a respiratory cycle. METHODS: A realistic nose model based on
      a multislice CT scan was created. The simulation was performed by the Software
      Fluent(r). Boundary conditions were based on previous in vivo measurements.
      Inhaled air had a temperature of 20(deg)C and relative humidity of 30%. The wall
      temperature was assumed to be variable from 34(deg)C to 30(deg)C with constant
      humidity saturation of 100% during the respiratory cycle. RESULTS: A substantial
      increase in temperature and humidity can be observed after passing the nasal
      valve area. Areas with high speed air flow, e.g. the space around the turbinates,
      show an intensive humidification and heating potential. Inspired air reaches 95%
      humidity and 28(deg)C within the nasopharynx. CONCLUSION: The human nose features
      an enormous humidification and heating capability. Warming and humidification are
      dependent on each other and show a similar spacial pattern. Concerning the
      climatisation function, the middle turbinate is of high importance. In contrast
      to in vivo measurements, numerical simulations can explore the impact of airflow
      distribution on nasal air conditioning. They are an effective method to
      investigate nasal pathologies and impacts of surgical procedures.

PMID- 22616077
TI  - Combined transnasal transcervical robotic dissection of posterior skull base:
      feasibility in a cadaveric model.
AB  - The current surgical trend is to expand the variety of minimally invasive
      approaches and, in particular,  the possible application of robotic surgery in
      head and neck surgery. For this purpose, we explored the feasibility of a
      combined transcervical-transnasal approach to the posterior skull base, using the
      da Vinci Surgical System in 3 cadaver heads. Superb visualization of the sellar,
      suprasellar and clival regions was possible in all three specimens. The trocars'
      placement through a transcervical port made a more cephalad visualization
      possible, eliminating the need to split the palate. The advantages of robotic
      surgery applied to the posterior cranial fossa are similar to the ones already
      clinically experienced in other districts (oropharynx, tongue base), in terms of
      tremor-free, bimanual, precise dissection. The implementation of instruments for
      bony work will definitely increase the applicability of such a system in the
      forthcoming years.

PMID- 22616078
TI  - Oral and intranasal steroid treatments improve nasal patency and paradoxically
      increase nasal nitric oxide in patients with severe nasal polyposis.
AB  - INTRODUCTION: Recently, we demonstrated that acoustic rhinometry (AR)
      measurements correlated with nasal cavity volumes in patients with nasal
      polyposis (NP). The aim of the present study was to evaluate whether AR and nasal
      nitric oxide (nNO) are useful methods in monitoring and follow-up of medical
      treatment of NP. MATERIAL AND METHODS: Patients with severe nasal polyps were
      randomized into two groups after a 4-week steroid washout period (w0): a
      treatment group received oral prednisone for 2 weeks (w2) and intranasal
      budesonide for 12 weeks (w12) while the control group received no steroid
      treatment. Nasal volume (Vol 0-6), minimum cross-sectional area (mCSA), nNO, peak
      nasal inspiratory flow (PNIF), nasal obstruction, and smell loss were evaluated.
      RESULTS: At w2, the treatment group showed a significant increase of vol 0-6
      compared to w0 and the control group. The mCSA area also increased compared to w0
      and the control group. At w12, the improvement in vol 0-6 and mCSA was maintained
      after intranasal steroids compared to w0. At w2, the treatment group showed a
      paradoxical increase of nNO compared to w0 and the control group. At w12, this
      increase was maintained by intranasal steroids. CONCLUSION: Both oral and
      intranasal steroid treatments improve nasal patency and paradoxically increase
      nNO, by opening the ostiomeatal complex. This suggests that AR and nNO are useful
      methods in the monitoring and follow-up of patients with NP.

PMID- 22616079
TI  - Olfaction after endoscopic sinus surgery: long-term results.
AB  - Loss of olfactory function is one of the main symptoms in patients with chronic
      rhinosinusitis. This prospective, non-randomized interventional study reports
      five years results of olfaction of patients with chronic rhinosinusitis who
      underwent endoscopic sinus surgery in conjunction with topical medical treatment.
      Forty-five patients with chronic rhinosinusitis who underwent endoscopic sinus
      surgery were evaluated preoperatively, after three months and 34 (76%) of them
      after five years. Olfactory function was assessed by a subjective visual analogue
      scale, by a screening test of olfaction with Smell Diskettes and by measuring the
      N-Butanol threshold. Patient's subjective sense of olfaction using a visual
      analogue scale was improved in 79% at 5 years. Objective measurements by Smell
      Diskettes improved in 53% at 5 years whilst the quantitative measurement by the N
      Butanol threshold improved in 85% at 5 years. The high percentage of patients
      with improvement of olfaction five years after surgery indicates that endoscopic
      sinus surgery in conjunction with continued topical treatment leads to a long
      term improvement of the sense of smell. However, it was found that - measured by
      the sensitive N-Butanol threshold - up to 9% had no improvement and 6% had
      deterioration in their olfaction at 5 years after endoscopic sinus surgery. This
      fact has to be considered in the preoperative counselling of patients.

PMID- 22616080
TI  - Are too many septal deviations operated on? A retrospective patient's
      satisfaction questionnaire with 11 years follow-up.
AB  - BACKGROUND: Not much is known about long-term satisfaction of septoplasty. The
      goal of this study was to assess disease specific quality of life outcomes as
      well as satisfaction at more than 10 years follow-up after septoplasty.
      METHODOLOGY/PRINCIPAL: The study was conducted as a retrospective questionnaire
      study (based on the NOSE scale) in which a questionnaire was sent to every
      patient and followed up by a telephone interview conducted in a tertiary
      otorhinolaryngologic clinic. RESULTS: 238 out of 369 patients who underwent
      septoplasty accepted to participate of which 222 were eligible. We found a
      significant reduction in NOSE score from 56.9 before surgery to 31.9 at follow
      up. 68.0% experienced improved nasal breathing and 55.9% were satisfied with the
      overall outcome. Predictive analysis showed that only severity of symptoms before
      surgery was predictive of all final outcome parameters. CONCLUSIONS: Long-term
      outcome of septoplasty appears to be in line with shorter follow-up. Surprisingly
      a sizable difference was noted between rate of satisfaction and improvement in
      nasal breathing. It is important that the surgeon and patient have the same
      expectations to septoplasty as to avoid any inappropriate disappointment, which
      is more likely to occur if symptoms are not severe.

PMID- 22616081
TI  - The microdebrider, a step forward or an expensive gadget?
AB  - BACKGROUND: Although the use of the microdebrider (shaver) is well known in
      endoscopic sinus surgery (FESS), there is lack of evidence from comparative
      studies focussing on the difference in operating time, intra-operative blood loss
      and user-friendliness between the microdebrider and traditional operating
      techniques. In this study we compared the use of the microdebrider to
      conventional instruments in FESS in these areas. METHODS: A prospective
      randomised double blind controlled trial in 60 patients with chronic
      rhinosinusitis with nasal polyposis (CRSwNP) undergoing bilateral FESS. Each
      subject received FESS using only traditional instruments (Blakseley forceps) on
      one side and the other side with the additional use of the microdebrider, this
      way serving as their own control. The primary outcome was operation time, intra
      operative blood loss and user friendliness and secondly safety and postoperative
      healing with a follow-up period at different time points up to three months
      postoperative. RESULTS: We found a 37% longer operating time when operating
      without a microdebrider. This difference was highly significant. The
      microdebrider scored significantly higher on every different parameter of user
      friendliness, except on the preparation of the instrument needed before surgery.
      For estimated blood loss during surgery we found no differences. Also there was
      no significant difference in postoperative healing at any point of time.
      CONCLUSIONS: This study demonstrates that operating patient with CRSwNP with the
      microdebrider is efficient and that the microdebrider at the same time is safe
      and easy to use.

PMID- 22616082
TI  - Juvenile angiofibroma: major and minor complications of preoperative
      embolization.
AB  - INTRODUCTION: Juvenile angiofibromas (JA) are highly vascular, benign tumours for
      which surgery is the treatment of choice. In most services, embolisation is
      performed prior to resection. Nevertheless, there are few data on the
      complications of preoperative embolisation for JA. AIM: To describe major and
      minor complications of preoperative embolisation in a 32-year experience of
      patients undergoing surgical resection of JA at a tertiary hospital. METHODS:
      Retrospective chart review study of 170 patients who underwent surgical resection
      of JA at a tertiary hospital between September 1976 and July 2008. RESULTS: All
      patients were male. Age ranged from 9 to 26 years. Ninety-one patients had no
      complications after embolisation. Overall, 105 complication events occurred of
      which four major and 101 minor. CONCLUSION: In our series, preoperative
      embolisation for JA produced no irreversible complications and no aesthetic or
      functional sequelae. The vast majority of complications were transient and
      amenable to clinical management.

PMID- 22616083
TI  - Sinonasal malignant melanoma: an analysis of 115 cases assessing outcomes of
      surgery, postoperative radiotherapy and endoscopic resection.
AB  - BACKGROUND: Melanomas account for 4% of sinonasal malignancies. We present the
      largest single institution series reported thus far and analyze the outcome with
      reference to lymph node involvement, radiotherapy and endoscopic resection.
      METHODOLOGY: Survival and recurrence data were analyzed on sinonasal melanoma
      cases collected from 1963-2010 to compare treatment strategies and to ascertain
      factors predicting outcome. RESULTS: 115 cases (mean age 65.9) were treated at
      our institution during this period. All underwent surgical resection of the
      tumour, 31 (27%) endoscopically, and 51 (44%) also received radiotherapy. Five
      year overall survival was 28% and disease-free survival was 23.7%. Local control
      was achieved for a median of 21 months, 5-year disease control rate of 27.7%.
      Endoscopically resected cases showed a significant overall survival advantage up
      to 5 years. Radiotherapy did not improve local control or survival. Cervical
      metastases conferred a dramatically worse outcome. CONCLUSIONS: Endoscopic
      resection of sinonasal melanoma does not prejudice outcome. The role of
      radiotherapy is unproven.

PMID- 22616085
TI  - How we do it: mini posterior septal artery flap for coverage after transphenoidal
      approaches.
AB  - We propose a novel posterior nasal flap for use in endoscopic approaches to the
      sella and parasellar region that involve resection of the sphenoid face and a
      posterior nasal septectomy.  It involves elevation of the mucosa of the posterior
      septum and sphenoid face with preservation of the angiosome based on the
      posterior septal artery.  This flap has the advantages of maximal mucosal
      preservation in order to optimize postoperative healing and has been demonstrated
      to permit future elevation of a complete naso-septal flap for reconstruction of
      anterior skull base defects.  An illustration of the technique is provided.

PMID- 22616084
TI  - Endonasal endoscopic approach for removal of intranasal nasal glial heterotopias.
AB  - BACKGROUND: Nasal Glial Heterotopias also called Nasal Gliomas (NG) are rare
      congenital tumours of the midline frontonasal space arising from a normal
      neurectodermal tissue entrapped during the closure of the anterior neuropore.
      Historically, such tumours were approached using a frontal craniotomy. The study
      aims to evaluate a fully endonasal endoscopic approach for intranasal NG removal.
      METHODS: We report a retrospective study of intranasal and mixed NG treated using
      endonasal endoscopic techniques and computer assisted navigation system from 1997
      to 2010 in two tertiary referral centres of Paediatric Otolaryngology. All
      tumours were investigated using two imaging modalities: craniofacial MRI and CT
      scan. RESULTS: Fifteen patients were included (0 to 14 years of age). All tumours
      were totally removed and no recurrence was observed after a mean follow-up of 32
      months. A skull base plasty was done in 13 cases to cover a bony defect or to
      treat a cerebrospinal leak. Nasal packing was usually removed 24 hours after
      surgery and all children were discharged home after 2 to 4 days. CONCLUSION:
      Removal of intranasal NGs using an endonasal endoscopic approach and a dedicated
      computer assisted navigation system is a safe and efficient procedure. Early
      management is recommended to treat neonatal airway obstruction.

PMID- 22616087
TI  - Charisma, status, and gender in groups with and without gurus.
AB  - A number of studies have noted that small religious groups with charismatic
      leaders seem to have different gender dynamics than do groups without. We argue
      that the presence of such a leader changes what charisma "means" in such a group.
      Without such a leader, strong personalities may appear charismatic and lead to
      positions of high status-and such dynamics historically have tended to be
      associated with a positional advantage to males. With such a leader, however,
      charisma is more likely to be compatible with receptivity and decoupled from
      gender characteristics that tend to disadvantage women, leading charismatic women
      to have greater status than they would otherwise have.

PMID- 22616088
TI  - Family structure, family disruption, and profiles of adolescent religiosity.
AB  - Youth in the United States are experiencing increasing numbers of family
      transitions as parents move in and out of marriages and cohabiting relationships.
      Using three waves of survey data from the National Study of Youth and Religion, I
      examine the relationship between family structure, parental breakup, and
      adolescent religiosity. A person-centered measure of the religiosity of
      adolescents is used to identify youth as Abiders, Adapters, Assenters, Avoiders,
      or Atheists and to assess movement of youth between the religious profiles
      between 2003 and 2008. Wave 1 family structure is not significantly related to
      religious change among adolescents at Wave 3. In contrast, the experience of a
      parental breakup is related to a change in religious profiles over time. Parental
      breakup is associated with religious decline among Abiders and Adapters, youth
      characterized by high levels of religious salience. However, among Assenters who
      are marginally tied to religion, a parental breakup or divorce is associated with
      increased religious engagement.

PMID- 22616089
TI  - "God must have been sleeping": faith as an obstacle and a resource for Rwandan
      genocide survivors in the United States.
AB  - In 1994, 1 million Rwandans were violently killed in only 100 days. Devastating
      for some Rwandan survivors was the significant role that some Catholic parishes
      and leaders took in ignoring, facilitating, and even perpetuating the genocide.
      This article seeks to understand how Rwandan genocide survivors draw on religion
      as they negotiate their postgenocide identities in the United States and
      comprehend their current faiths, beliefs, and practices. Based on qualitative
      interviews with Rwandan survivors now located within the United States, I argue
      that the experiences of religiosity postgenocide serve as both an obstacle and a
      resource in postgenocide life, creating significant individual and local
      ramifications for community engagement, reconciliation, and trauma recovery.

PMID- 22616090
TI  - Pornography, religion, and the happiness gap: does pornography impact the
      actively religious differently?
AB  - Club good models developed by economists suggest that the club provides a benefit
      to members by fostering the provision of semi-public goods. In the case of
      religion, churches create enforcement mechanisms to reduce free riding.
      Consequently, the psychic costs of deviant activity should be higher for
      individuals who belong to religious groups with strong social norms. Data from
      the General Social Survey are used to examine whether the cost of using
      pornography is greater for the more religiously involved. We measure the cost of
      using pornography as the happiness gap or the gap between the average happiness
      reported by individuals who do and individuals who do not report using
      pornography. The happiness gap is larger for individuals who regularly attend
      church and who belong to religious groups with strong attitudes against
      pornography.

PMID- 22616091
TI  - Contribution of monaural and binaural cues to sound localization in listeners
      with acquired unilateral conductive hearing loss: improved directional hearing
      with a bone-conduction device.
AB  - Sound localization in the horizontal (azimuth) plane relies mainly on interaural
      time differences (ITDs) and interaural level differences (ILDs). Both are
      distorted in listeners with acquired unilateral conductive hearing loss (UCHL),
      reducing their ability to localize sound. Several studies demonstrated that UCHL
      listeners had some ability to localize sound in azimuth. To test whether
      listeners with acquired UCHL use strongly perturbed binaural difference cues, we
      measured localization while they listened with a sound-attenuating earmuff over
      their impaired ear. We also tested the potential use of monaural pinna-induced
      spectral-shape cues for localization in azimuth and elevation, by filling the
      cavities of the pinna of their better-hearing ear with a mould. These conditions
      were tested while a bone-conduction device (BCD), fitted to all UCHL listeners in
      order to provide hearing from the impaired side, was turned off. We varied
      stimulus presentation levels to investigate whether UCHL listeners were using
      sound level as an azimuth cue. Furthermore, we examined whether horizontal sound
      localization abilities improved when listeners used their BCD. Ten control
      listeners without hearing loss demonstrated a significant decrease in their
      localization abilities when they listened with a monaural plug and muff. In 4/13
      UCHL listeners we observed good horizontal localization of 65 dB SPL broadband
      noises with their BCD turned off. Localization was strongly impaired when the
      impaired ear was covered with the muff. The mould in the good ear of listeners
      with UCHL deteriorated the localization of broadband sounds presented at 45 dB
      SPL. This demonstrates that they used pinna cues to localize sounds presented at
      low levels. Our data demonstrate that UCHL listeners have learned to adapt their
      localization strategies under a wide variety of hearing conditions and that sound
      localization abilities improved with their BCD turned on.

PMID- 22616093
TI  - Diabetes.

PMID- 22616092
TI  - Improving virtual channel discrimination in a multi-channel context.
AB  - Improving spectral resolution in cochlear implants is key to improving
      performance in difficult listening conditions (e.g. speech in noise, music,
      etc.). Current focusing might reduce channel interaction, thereby increasing
      spectral resolution. Previous studies have shown that combining current steering
      and current focusing reduces spread of excitation and improves virtual channel
      discrimination in a single-channel context. It is unclear whether the single
      channel benefits from current focusing extend to a multi-channel context, in
      which the physical and perceptual interference of multiple stimulated channels
      might overwhelm the benefits of improved spectral resolution. In this study,
      signal discrimination was measured with and without current focusing, in the
      presence of competing stimuli on nearby electrodes. Results showed that signal
      discrimination was consistently better with current focusing than without,
      regardless of the amplitude of the competing stimuli. Therefore, combining
      current steering and current focusing may provide more effective spectral cues
      than are currently available.

PMID- 22616094
TI  - Diabetes in numbers.

PMID- 22616095
TI  - Immunomodulators: Cell savers.

PMID- 22616096
TI  - Medical devices: Managed by machine.

PMID- 22616097
TI  - Perspective: Rethink the immune connection.

PMID- 22616098
TI  - Pathology: Cause and effect.

PMID- 22616099
TI  - Microbiome: The critters within.

PMID- 22616100
TI  - Public health: India's diabetes time bomb.

PMID- 22616101
TI  - Perspective: Testing failures.

PMID- 22616102
TI  - Prevention: Nipped in the bud.

PMID- 22616103
TI  - Skies darken over drug companies.

PMID- 22616104
TI  - Many US cancer survivors still lost in transition.

PMID- 22616105
TI  - Drunk driving across the globe: let's learn from one another.

PMID- 22616106
TI  - Multiple ring-enhancing lesions in the brain.

PMID- 22616107
TI  - Hypoglossal nerve palsy after extensive vomiting.

PMID- 22616108
TI  - ApiNATOMY: a novel toolkit for visualizing multiscale anatomy schematics with
      phenotype-related information.
AB  - A significant proportion of biomedical resources carries information that cross
      references to anatomical structures across multiple scales. To improve the
      visualization of such resources in their anatomical context, we developed an
      automated methodology that produces anatomy schematics in a consistent manner,and
      provides for the overlay of anatomy-related resource information onto the same
      diagram. This methodology, called ApiNATOMY, draws upon the topology of ontology
      graphs to automatically lay out treemaps representing body parts as well as
      semantic metadata linking to such ontologies. More generally, ApiNATOMY treemaps
      provide an efficient and manageable way to visualize large biomedical ontologies
      in a meaningful and consistent manner. In the anatomy domain, such treemaps will
      allow epidemiologists, clinicians, and biomedical scientists to review, and
      interact with, anatomically aggregated heterogeneous data and model resources.
      Such an approach supports the visual identification of functional relations
      between anatomically colocalized resources that may not be immediately amenable
      to automation by ontology-based inferencing. We also describe the application of
      ApiNATOMY schematics to integrate, and add value to, human phenotype-related
      information-results are found at http://apinatomy.org. The long-term goal for the
      ApiNATOMY toolkit is to support clinical and scientific graphical user interfaces
      and dashboards for biomedical resource management and data analytics.

PMID- 22616109
TI  - Current situations and challenges of occupational disease prevention and control
      in China.
AB  - China is one of ancient countries with nearly 5,000 yr history of civilization,
      with land area of 9,600,000 km2, including 4 municipalities, 23 provinces, 5
      autonomous regions and 2 special administrative regions. There are 56 nations and
      1.37 billion peoples (2010, November). In 2010, GDP was 40120.2 billion Yuan, and
      per capita GDP was 3,600 dollars. Employment population nearly reached 780
      million peoples, including a total of 226 million migrant workers. At present,
      China is in the rapid development period of industrialization, urbanization and
      globalization, and workers face the traditional and novel dual occupational
      hazards. Also, prevention and control of occupational disease faces severe
      situations and challenges.

PMID- 22616111
TI  - 'One size fits all' health policies crippling rural rehab-therapists.

PMID- 22616113
TI  - PE eye department carves up cataract surgery record book.

PMID- 22616112
TI  - Tighter medical parole - no more 'Shaik, rattle and roll'.

PMID- 22616110
TI  - Ethanol withdrawal-induced brain metabolites and the pharmacological effects of
      acamprosate in mice lacking ENT1.
AB  - Acamprosate is clinically used to treat alcohol-dependent patients. While the
      molecular and pharmacological mechanisms of acamprosate remain unclear, it has
      been shown to regulate gamma-aminobutyric acid (GABA) or glutamate levels in the
      cortex and striatum. To investigate the effect of acamprosate on brain
      metabolites in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc),
      we employed in vivo 16.4 T proton magnetic resonance spectroscopy. We utilized
      type 1 equilibrative nucleoside transporter (ENT1) null mice since acamprosate
      attenuates ethanol drinking in these mice. Our findings demonstrated that ethanol
      withdrawal reduced GABA levels and increased phosphorylated choline compounds in
      the mPFC of both wild-type and ENT1 null mice. Notably, acamprosate normalized
      these withdrawal-induced changes only in ENT1 null mice. In the NAc, ethanol
      withdrawal increased glutamate and glutamine (Glx) levels only in wild-type mice.
      Interestingly, acamprosate reduced Glx levels in the NAc compared to the
      withdrawal state in both genotypes. These results provide a molecular basis for
      the pharmacological effect of acamprosate in the cortical-striatal circuit.

PMID- 22616114
TI  - Isolated in a technologically connected world?: Changes in the core professional
      ties of female researchers in Ghana, Kenya, and Kerala, India.
AB  - Using panel data gathered across two waves (2001 and 2005) from researchers in
      Ghana, Kenya, and Kerala, India, we examine three questions: (1) To what extent
      do gender differences exist in the core professional networks of scientists in
      low-income areas? (2) How do gender differences shift over time? (3) Does use of
      information and communication technologies (ICTs) mediate the relationship
      between gender and core network composition? Our results indicate that over a
      period marked by dramatic increases in access to and use of various ICTs, the
      composition and size of female researchers core professional ties have either not
      changed significantly or have changed in an unexpected direction. Indeed, the
      size of women's ties are retracting over time rather than expanding.

PMID- 22616115
TI  - Race and imprisonments: vigilante violence, minority threat, and racial politics.
AB  - The effects of lynchings on criminal justice outcomes have seldom been examined.
      Recent findings also are inconsistent about the effects of race on imprisonments.
      This study uses a pooled time-series design to assess lynching and racial threat
      effects on state imprisonments from 1972 to 2000. After controlling for
      Republican strength, conservatism, and other factors, lynch rates explain the
      growth in admission rates. The findings also show that increases in black
      residents produce subsequent expansions in imprisonments that likely are
      attributable to white reactions to this purported menace. But after the
      percentage of blacks reaches a substantial threshold-and the potential black vote
      becomes large enough to begin to reduce these harsh punishments-reductions in
      prison admissions occur. These results also confirm a political version of racial
      threat theory by indicating that increased Republican political strength produces
      additional imprisonments.

PMID- 22616117
TI  - The influence of world societal forces on social tolerance. A time comparative
      study of prejudices in 32 countries.
AB  - Societal variation in xenophobia, homophobia, and other prejudices is frequently
      explained by the economic background and political history of different
      countries. This article expands these explanations by considering the influence
      of world societal factors on individual attitudes. The empirical analysis is
      based on survey data collected within the World Value Survey and European Values
      Study framework between 1989 and 2010. Data are combined to a three-wave cross
      sectional design including about 130,000 respondents from 32 countries. Results
      show that xenophobia and homophobia are influenced by the national political
      history, societal affluence, and the presence of international organizations.
      Global forces, however, are of particular importance for homophobia.

PMID- 22616119
TI  - Activating diversity: the impact of student race on contributions to course
      discussions.
AB  - Racial diversity is understood to play an important role for all students on the
      college campus. In recent years, much effort has gone into documenting the
      positive effects of this diversity. However, few studies have focused on how
      diversity impacts student interactions in the classroom, and even fewer studies
      attempt to quantify contributions from students of different races. Using Web
      blog discussions about race and religion, the authors uncover the differences in
      contributions black and white students make to those discussions. The
      implications of these findings are important for scholars interested in how
      diversity impacts student learning, and for policymakers advocating on behalf of
      affirmative action legislation.

PMID- 22616120
TI  - What's nature got to do with it? A situated historical perspective on socio
      natural commodities.
AB  - Nature(s) have been commodified since the early days of capitalism, but through
      processes and socio-natural relationships mediated by their times, histories and
      localities. While the conditions under which nature's commodities are being
      trademarked today may be new, their potential for commodification is not.
      Commodifications of nature should not come as a surprise to environmental social
      scientists and activists. In this article, I argue that commodification of
      'nature's products, places and processes' produces new sorts of socio-natures.
      Situated histories of rubber are particularly relevant because, like carbon,
      ecosystem services and other recently commodified natures, rubber sits
      comfortably on the line between a fictitious commodity and a commodity produced
      explicitly for market: the latex alone has almost no use value, and to give it
      any exchange value, it requires processing. Yet analytically, it is still
      considered a 'natural commodity', different from 'synthetic rubber' and other
      tradable tree latexes in qualities and socio-natural characteristics. However, it
      is the social relations constituting rubber's production and trade in various
      rainforest and agro-forestry environments that have given it a positive or
      negative connotation, rather than its natural properties or the ecological
      contexts within which it has been produced. By situating rubber in three of its
      globally important temporal and spatial contexts, I show how it has been
      subjected to fairy-tale-like stories that masked and naturalized its commodity
      lives of the moment. Understanding how history is told or remains untold is thus
      an essential part of the politics of knowledge production, but also of human
      experience and mobilization for change. It should be part of any political
      ecology analysis.

PMID- 22616121
TI  - The contradictory logic of global ecosystem services markets.
AB  - Commodification and transnational trading of ecosystem services is the most
      ambitious iteration yet of the strategy of 'selling nature to save it'. The World
      Bank and UN agencies contend that global carbon markets can slow climate change
      while generating resources for development. Consonant with 'inclusionary'
      versions of neoliberal development policy, advocates assert that international
      payment for ecosystem services (PES) projects, financed by carbon-offset sales
      and biodiversity banking, can benefit the poor. However, the World Bank also
      warns that a focus on poverty reduction can undermine efficiency in conservation
      spending. The experience of ten years of PES illustrates how, in practice, market
      efficiency criteria clash directly with poverty-reduction priorities.
      Nevertheless, the premises of market-based PES are being extrapolated as a model
      for global REDD programmes financed by carbon-offset trading. This article argues
      that the contradiction between development and conservation observed in PES is
      inevitable in projects framed by the asocial logic of neoclassical economics.
      Application in international conservation policy of the market model, in which
      profit incentives depend upon differential opportunity costs, will entail a net
      upward redistribution of wealth from poorer to wealthier classes and from rural
      regions to distant centres of capital accumulation, mainly in the global North.

PMID- 22616124
TI  - Biodiversity for billionaires: capitalism, conservation and the role of
      philanthropy in saving/selling nature.
AB  - This article examines the role of philanthropy in conservation as a way of
      exploring how and why conservation might be becoming more neoliberal. It
      describes how conservation philanthropy supports capitalism both discursively and
      in more practical ways. Philanthropy is examined in terms of the two forces
      considered to be driving the neoliberalization of conservation - the need for
      capitalism to find new ways of making money, and the desire of conservationists
      to engage with capitalism as the best way of getting things done. It demonstrates
      how philanthropy can speak to both of these logics simultaneously, particularly
      through emerging ideas of philanthrocapitalism, which may be enhancing the
      neoliberalization of both philanthropy and conservation.

PMID- 22616123
TI  - "TEEB begins now": a virtual moment in the production of natural capital.
AB  - This article uses theories of virtualism to analyse the role of The Economics of
      Ecosystems and Biodiversity (TEEB) project in the production of natural capital.
      Presented at the 10th Conference of the Parties to the Convention on Biological
      Diversity, the project seeks to redress the 'economic invisibility of nature' by
      quantifying the value of ecosystems and biodiversity. This endeavour to put an
      economic value on ecosystems makes nature legible by abstracting it from social
      and ecological contexts and making it subject to, and productive of, new market
      devices. In reducing the complexity of ecological dynamics to idealized
      categories TEEB is driven by economic ideas and idealism, and, in claiming to be
      a quantitative force for morality, is engaged in the production of practices
      designed to conform the 'real' to the virtual. By rendering a 'valued' nature
      legible for key audiences, TEEB has mobilized a critical mass of support
      including modellers, policy makers and bankers. We argue that TEEB's rhetoric of
      crisis and value aligns capitalism with a new kind of ecological modernization in
      which 'the market' and market devices serve as key mechanisms to conform the real
      and the virtual. Using the case of TEEB, and drawing on data collected at COP10,
      we illustrate the importance of international meetings as key points where
      idealized models of biodiversity protection emerge, circulate and are negotiated,
      and as sites where actors are aligned and articulated with these idealized models
      in ways that begin further processes of conforming the real with the virtual and
      the realization of 'natural capital'.

PMID- 22616125
TI  - Consuming the forest in an environment of crisis: nature tourism, forest
      conservation and neoliberal agriculture in south India.
AB  - This article engages ethnographically with the neoliberalization of nature in the
      spheres of tourism, conservation and agriculture. Drawing on a case study of
      Wayanad district, Kerala, the article explores a number of themes. First, it
      shows how a boom in domestic nature tourism is currently transforming Wayanad
      into a landscape for tourist consumption. Second, it examines how tourism in
      Wayanad articulates with projects of neoliberalizing forest and wildlife
      conservation and with their contestations by subaltern groups. Third, it argues
      that the contemporary commodification of nature in tourism and conservation is
      intimately related to earlier processes of commodifying nature in agrarian
      capitalism. Since independence, forest land has been violently appropriated for
      intensive cash-cropping. Capitalist agrarian change has transformed land into a
      (fictitious) commodity and produced a fragile and contested frontier of
      agriculture and wildlife. When agrarian capitalism reached its ecological limits
      and entered a crisis of accumulation, farming became increasingly speculative,
      exploring new modes of accumulation in out-of-state ginger cultivation. In this
      scenario nature and wildlife tourism emerges as a new prospect for accumulation
      in a post-agrarian economy. The neoliberalization of nature in Wayanad, the
      authors argue, is a process driven less by new modes of regulation than by the
      agrarian crisis and new modes of speculative farming.

PMID- 22616126
TI  - James Hinton and Victorian individuality: polygamy and the sacrifice of the self.

PMID- 22616127
TI  - [A survey of compliance to oral anti-cancer drugs in outpatients].

PMID- 22616128
TI  - Poetry and clover therapies bolster patients.

PMID- 22616129
TI  - [Contemporary Chinese historiography's response to psychohistory].

PMID- 22616131
TI  - [On the role of the British government in the postwar    housing development].

PMID- 22616132
TI  - [The problem of prostitution during China's early    urban modernization].

PMID- 22616133
TI  - [The development of agriculture by migrants in northeastern China during    the
      1920's].

PMID- 22616134
TI  - [Peasant migration and urban social problems in modern China].

PMID- 22616135
TI  - [A critique of utopia, eschatology, and historical    progress in Western
      historiography].

PMID- 22616136
TI  - Commentary on Peter Eyre's personal perspective on all-purpose veterinary
      education.

PMID- 22616137
TI  - International Conference on Harmonisation; addendum to International Conference
      on Harmonisation Guidance on S6 Preclinical Safety Evaluation of Biotechnology
      Derived Pharmaceuticals; availability. Notice.
AB  - The Food and Drug Administration (FDA) is announcing the availability of a
      guidance entitled "S6 Addendum to Preclinical Safety Evaluation of Biotechnology
      Derived Pharmaceuticals'' (S6 addendum). The S6 addendum was prepared under the
      auspices of the International Conference on Harmonisation of Technical
      Requirements for Registration of Pharmaceuticals for Human Use (ICH). The S6
      addendum is intended to incorporate new knowledge and experience gained since the
      implementation of the ICH guidance entitled "S6 Preclinical Safety Evaluation of
      Biotechnology-Derived Pharmaceuticals'' (ICH S6) and to clarify and provide
      greater detail to enable the development of safe and effective
      biopharmaceuticals.

PMID- 22616138
TI  - The impact of AVMA COE's accreditation on veterinary medical education.
AB  - Point 1: the American Veterinary Medical Association Council on Education's (AVMA
      COE's) accreditation pro-cess is aimed at minimum training for entry-level
      veterinarians. This has a two-fold consequence: 1. The opportunity to discover
      the absolute minimum number of necessary resources is opened. While this is a
      threat to the standard model of veterinary education, it might have value if it
      is cost-efficient and students graduate with minimal or no debt. 2. There is no
      mechanism to measure training,research, or service programs above the minimum or
      beyond the entry level. Point 2: the implication of the minimum entry-level
      general standard is also two-fold: 1. We must measure performance above the mini
      mum. A separate process is necessary (a) to develop and implement objective
      metrics and (b) to publicize superior achievement as opposed to minimal
      performance. 2. We must measure and publicize institutions or programs that
      advance the field beyond training entry-level veterinarians. Service, research,
      and training aimed at advancing the field, providing leadership, and improving
      public health and safety(One Health) require separate measurement and advocacy in
      order to obtain and justify the necessary resources. I conclude that in the
      absence of a new process by which to measure excellence, market forces will push
      the entire profession toward the most cost-effective method of providing minimal
      training for entry-level veterinarians. But what about the far more expensive
      goal of providing a global public good of which our profession is so proud?The
      public health and safety mission of veterinary medi-cine, including the entire
      One Health initiative, requires separate measurement in order to give objective
      metrics to the institutions and components of the profession committed to those
      goals to pursue vigorous advocacy and obtain or retain the necessary resources.

PMID- 22616139
TI  - Reviving full-service family practice in British Columbia.
AB  - In 2003, British Columbia created a joint committee of doctors and government
      representatives to reverse the deterioration in full-service family practice,
      particularly evidenced in poor morale among family physicians. The committee
      introduced an array of innovative programs into the province's fee-for-service
      system of solo and small-group practices, focusing on operational rather than
      structural changes. Incentive payments for managing chronically ill patients were
      followed by maternity care bonuses, training to enhance clinical skills and to
      support practice redesign, recruitment incentives for new family doctors, and
      other patient care initiatives. The programs, which are open to all general
      practitioners, have reduced health care spending on high-needs patients, research
      shows. Moreover, British Columbia now has the lowest hospitalization rate in
      Canada for seven medical conditions. The experience dem-onstrates that
      coordinated, operational reform of full-service family practice can improve care
      and reduce costs without radical restructuring of the primary care system.

PMID- 22616140
TI  - [Writing a scientific paper].

PMID- 22616141
TI  - Alterations in pancreatic protein expression in STZ-induced diabetic rats and
      genetically diabetic mice in response to treatment with hypoglycemic dipeptide
      Cyclo (His-Pro).
AB  - To provide insights into the molecular mechanisms underlying diabetes mellitus,
      we performed a proteomic study on two diabetic animal models, streptozotocin
      (STZ)-induced diabetic rats (T1DM) and genetically diabetic (C57BL/6J ob/ob) mice
      (T2DM). To better understand the recovery process of those diabetic rodents, we
      examined the effect of hypoglycemic dipeptide Cyclo (His-Pro) (CHP) treatment on
      the differential expression of pancreatic proteins in both animal models. Oral
      administration of CHP had an excellent hypoglycemic effect in both animal models,
      lowering the average plasma glucose level by over 50%. Pancreatic proteins were
      separated by two-dimensional gel electrophoresis (2-DE) and identified by MALDI
      TOF mass spectrometry. This study allowed, for the first time, the identification
      of 34 proteins that are related to diabetes and potential targets of CHP, a
      potent anti-diabetic agent for both T1DM and T2DM. The alterations in the
      expression of these proteins could indicate a tendency for diabetic animals to
      overcome their diabetic state. These proteins are involved in cellular functions
      such as metabolism, cellular structure, oxidative stress, as well as signal and
      energy transduction. Some have already been linked to diabetes, suggesting that
      the newly identified proteins might also be significant in the etiology of this
      pathology and should be further investigated. Furthermore, CHP has emerged as a
      potent tool for both the treatment and study of the molecular mechanisms
      underlying diabetes. Thus, the findings presented here provide new insights into
      the study and potential treatment of this pathology.

PMID- 22616143
TI  - [Challenges and trends in pulmonary medicine].
AB  - Several breakthrough discoveries have led to substantial improvements in the
      quality of pulmonary medicine, as well as to new medications, techniques, and
      toots. This issue of "Harefuah" is dedicated to the current knowledge in
      pulmonary research and medicine, novel discoveries in the field, and challenges
      for the future. One paper adds informative data about COPD while another provides
      a review that summarizes the development of asthma therapy and the potential
      clinical use of omalizumab for the treatment of severe, allergic asthma. This
      issue provides new information regarding the various modalities of endoscopic
      treatment for patients with emphysema, and the role of pulmonary rehabilitation
      in pulmonary fibrosis. Encouraging data are provided regarding coagulation
      disease in acute tuberculosis and uncommon malignancies, such as adenocystic
      carcinoma of the bronchial tree. Additional papers illuminate recent discoveries
      in the field of COPD, including the role of pleural effusion in anemic patients
      admitted to intensive care units. Overall, this issue of Harefuah provides
      important updates regarding advances in pulmonary medicine in 2012.

PMID- 22616142
TI  - Gender-dependent protein expression in white adipose tissues of lean and obese
      rats fed a high fat diet.
AB  - BACKGROUND: Proper understanding of molecular mechanisms underlying gender
      dimorphism in obesity for better nutritional recommendation is still in early
      stages. As white adipose tissues (WAT) is most important tissue in obesity
      metabolism, comparative proteomic analysis of all three WAT deposits at the same
      time to yield immensely important protein markers was the primary goal of this
      study. METHODS: We performed differential expression analysis of protein profiles
      of three different WAT viz. subcutaneous, inguinal, and abdominal fat deposits of
      both genders in lean and obese rats fed a high fat diet (HFD) using a combination
      of 2-DE and MALDI-TOF-MS. RESULTS: The proteomics analysis enabled us to detect
      25, 29, and 46 proteins showing gender differences in three WAT deposits,
      respectively, to gain insight into cause of higher body weight gain in male in
      response to HFD. CONCLUSION: The gender dimorphism found in this proteomic study
      implies that female rats have a lower tendency to undergo metabolic syndrome
      manifestation, which is associated with lower reliance on lipid as an energy
      fuel, lower lipogenesis, as well as increased mitochondrial oxidative capacity.
      In conclusion, most of the candidate proteins identified herein by differential
      proteomics were previously unrecognized in gender dimorphism of adipose tissue.

PMID- 22616144
TI  - [Pleural effusion in chronic obstructive pulmonary medicine (COPD) patients in a
      medical intensive care unit: characteristics and clinical implications].
AB  - BACKGROUND: Pleural effusions are common among patients admitted to an Intensive
      Care Unit (ICU). AIM: To retrospectively assess the role of pleural effusions in
      chronic obstructive pulmonary disease (COPD) patients admitted to a Medical ICU
      (MICU). PATIENTS AND METHODS: We reviewed records of patients admitted over 12
      months to the MICU with a diagnosis of COPD. We colLected clinical and laboratory
      data for their entire MICU stay. A radiologist reviewed all chest radiographs to
      determine the presence and estimated volume of pleural effusions. RESULTS: A
      total of 100 consecutive patients with COPD admitted to the MICU were included;
      32 (32%) developed pleural effusions. COPD exacerbations were more common among
      patients without pleural effusion. Congestive heart failure (CHF) exacerbations
      were more common among patients with pleural effusions (p=0.001 and p=0.006,
      respectively). The length of stay was significantly longer among COPD patients
      with a pleural effusion (19 +/- 8 days) than those without it (14 +/- 3 days,
      p=0.001). The mortality rate was similar (40%) in both groups. Only patients with
      a large or unexplained effusion (19%) underwent thoracocentesis. In all cases,
      the pleural fluids were transudate and confirmed the diagnosis of CHF.
      CONCLUSIONS: Pleural effusion is common among COPD patients admitted to a MICU.
      Most are due to CHF and parapneumonic effusions and respond well to treatment of
      the underlying problem.

PMID- 22616145
TI  - [Tracheobronchial adenoid cystic carcinoma: seven case reports].
AB  - BACKGROUND: Adenoid cystic carcinoma of the respiratory tract is a rare form of
      malignant neoplasm that arises from salivary glands. A surgical resection with or
      without radiotherapy is commonly recommended. For inoperable patients,
      radiotherapy and endobronchial treatment, which include laser and stent
      insertion, are important therapeutic modalities. AIM: To summarize our experience
      in adenocystic carcinoma of the respiratory tract. METHODS: Seven patients with
      adenoid cystic carcinoma were diagnosed and treated in the Pulmonary Institute at
      Rabin Medical Center, a tertiary care hospital in central Israel in 2000-2006.
      RESULTS: Three patients were men and four were women, with a presenting age at
      diagnosis ranging from 31 to 79 years. All the patients were nonsmokers. Major
      symptoms at presentation included dry cough, dyspnea and hemoptysis. Only two
      patients were operable at time of presentation and 4 patients had local and
      distant metastases. In 6 patients the tumor was presented in the trachea with
      marked obstruction of the tracheal lumen. In 4 patients coexisting lesions in the
      main bronchus were also found. Two patients with non-metastatic disease underwent
      surgical resection with external radiation. Multiple laser therapy and
      brachytherapy were performed in 4 patients. Two patients with severe airway
      stenosis that was resistant to radiotherapy were treated with laser and
      intratracheal stent replacement. CONCLUSIONS: Endobronchial therapy that includes
      brachytherapy, laser and stent insertion, is a useful therapeutic modality for
      the treatment of patients with adenoid cystic carcinoma of the respiratory tract
      who are resistant to radiotherapy.

PMID- 22616146
TI  - [Actinomyces empyema treated with decortications].
AB  - Actinomyces infections are rare infections, involving the head and neck,
      abdominal cavity, and the lung. We report a case of a 66 year old woman with
      shortness of breath and a pleural effusion from which Actinomyces meyeriwas
      cultured. The diagnosis was confirmed by the polymerase chain reaction technique.
      The infection was successfully treated with a combination of ampicillin and
      surgical decortication. Due to their rarity, Actinomyces infections are not often
      suspected. These infections are difficult to diagnose due to specific
      microbiologic requirements for isolation of Actinomyces. In many reviewed cases
      of Actinomyces infection, patients underwent surgery for presumed cancer but were
      eventually diagnosed as being infected with actinomycosis. Due to lack of
      improvement of our patient, surgical decortication was performed, which led to a
      successful outcome.

PMID- 22616147
TI  - [Incidence of venous thromboembolism in 700 patients with acute tuberculosis].
AB  - BACKGROUND: Studies have demonstrated a link between pulmonary tuberculosis and
      hypercoagulable state, with reported rates of 3-10% venous thromboembolism (VTE)
      in all adults with tuberculosis. However, the latest research was conducted
      almost 18 years ago. AIM: The present study aims to evaluate the current
      incidence and characteristics of VTE in a large sample of patients with acute
      tubercuLosis. METHODS: The study included 700 adults treated for tuberculosis
      from 1999 to 2007.The files were reviewed for Length of hospital stay, occurrence
      of VTE, site of VTE, interval from onset of tuberculosis/treatment to VTE, and
      outcome. To exclude primary hypercoagulable state, all patients with VTE
      underwent a complete hypercoagulation profile. RESULTS: VTE was noted in 5 of the
      700 patients (0.7%). Ages ranged from 19 to 70 years (median 53). All had
      pulmonary tuberculosis; median hospital stay was 28 days (range, 26-44 days). All
      cases of VTE occurred within the first month of treatment. All 5 patients had
      deep vein thrombosis, and one also subsequently developed a pulmonary embolism.
      All patients responded to anticoagulation treatment. CONCLUSION: VTE occurs in 1
      out of every 140 patients with acute tuberculosis. It seems to deveLop mainly in
      the first month of treatment, especially in those with a prolonged hospital stay.
      Outcome is good.

PMID- 22616148
TI  - [Incidence of hospitalizations among chronic obstructive pulmonary disease (COPD)
      patients with anemia].
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by
      progressive exertional and resting dyspnea and is associated with major co
      morbidities. Hemoglobin level disorders (anemia and polycythemia) prevalence
      among patients and the relationship between them and the clinical expression are
      still not characterized unequivocally. The main purpose of this work is to test
      the association between anemia and hospitalizations. The presence of such a link
      may promote the diagnosis and treatment aimed at the patient's hemoglobin levels.
      HYPOTHESIS: Anemia in patients with COPD is associated with an increased number
      of hospitalizations. METHODS: A retrospective cohort study analysis, conducted on
      a group of COPD patients (n = 333) followed in the Pulmonology Institute of the
      Soroka University Medical Center in the years 2003-2009. Demographic
      physiological and clinical characteristics were compared between anemic,
      polycythemic and normal hemoglobin patients. Using statistical models, we
      examined the relationship between the presence of anemia and clinical outcome.
      RESULTS: Anemia was found in 79 patients (24%) and polycythemia among seven
      patients (2%). No difference was found between the groups in terms of number of
      hospitalizations, number of hospitalization days and ventilator events. There was
      a higher rate of co-morbidities (such as heart failure, chronic kidney disease)
      among anemic patients. There were also lower values of BMI and lung function and
      a higher proportion of men among anemic patients. CONCLUSIONS: Anemia in patients
      with COPD was not associated with an increase in the number of severe
      exacerbations. More studies are needed to clarify the threshold of a hemoglobin
      level below which there is an increase in the rate of hospitalizations.

PMID- 22616149
TI  - [Omalizumab treatment in patients with asthma: summary of Meir Medical Center
      experience with 47 patients].
AB  - INTRODUCTION: Omalizumab is a humanized monoclonal anti-IgE for the treatment of
      moderate to severe allergic asthma. Although the treatment has been available for
      several years, there are some concerns about its safety and efficacy. AIM: To
      assess the efficacy and safety of Omalizumab in all asthmatic patients who were
      treated with Omalizumab during at least 3 months in the Pulmonary Department at
      the Meir Medical Center. METHODS: Retrospective analysis was conducted for all
      our asthmatic patients. Demographic and clinical characteristics of the patients
      were recorded from the computerized system of the Clalit Medical Service. Data
      collected included the degree of severity of the asthma, steroids usage, rate of
      asthma exacerbations, hospitalizations before and with Omalizumab treatment, as
      well as the safety profile. RESULTS: Forty seven patients were included in the
      study; 70% were female; mean age was 61 +/- 12 years. Duration of asthma was 25
      +/- 17 years. Asthma exacerbations rate decLined from 70.2% to 38.3% (p=0.007).
      Pulmonary functions improved from 58 +/- 14% FEV1 to 63 +/- 17% (p=0.002). Forty
      five percent of the patients had no hospitalizations during the Omalizumab
      treatment; 25% had one hospitalization, 17% two and 13% had 3 or more
      hospitalizations. No anaphylaxis or malignancies were observed. No serious
      adverse events were noticed except for 4 patients with injection site pain.
      CONCLUSIONS: Data indicates that the high efficacy of add-on Omalizumab in
      patients with moderate to severe allergic asthma is accompanied by an acceptable
      safety profile.

PMID- 22616150
TI  - [The role of pulmonary rehabilitation in idiopathic pulmonary fibrosis].
AB  - Idiopathic pulmonary fibrosis (IPF) is the most common interstitial lung disease
      (ILD) characterized by exertional dyspnea, hypoxemia and exercise intolerance.
      The pathophysiology of IPF usually presents restrictive physiology of lung volume
      and impaired gas exchange. Most of the research which supports the effectiveness
      of pulmonary rehabilitation (PR) comes from chronic obstructive pulmonary disease
      (COPD) patients' studies. However, in the past few years growing evidence has
      emerged to support the effectiveness and safety of PR programs in IPF patients.
      Exercise training in PR programs was shown to increase exercise and functional
      capacity, decreasing shortness of breath and improving quality of life in IPF
      patients. Nevertheless, PR guidelines for IPF patients have not yet been
      established. This review presents the current existing data on the effectiveness
      of PR programs in IPF patients. Large and well controlled trials are needed for
      the establishment of clinical guidelines of PR in IPF patients.

PMID- 22616151
TI  - [Perspectives in future asthma therapy].
AB  - Five to ten percent of all asthmatics, many dozens of millions of patients all
      over the world, do not respond to maximal medical therapy, including systemic
      steroids, and the toll of treating them constitutes about eighty percent of the
      total cost of managing all asthmatics. Other asthmatics who do respond to medical
      therapy either are not compliant with their medications or suffer from disabling
      adverse effects. The future therapy of asthma will concentrate on finding medical
      solutions to these sub-groups of patients but the entire asthmatic population
      will enjoy its achievements. The future trends in asthma therapy include
      immunomodulation, managing receptors and inflammatory mediators that are crucial
      in asthma pathogenesis, formulation of custom-made medications using individual
      pharmacogenetics, elaborated specific immunotherapy of atopic rhinitis,
      development of "smart inhalers" and sophisticated techniques in aerosol
      transportation to the airways, and bronchial thermoplasty which has only recently
      been approved. The daily clinical implications of these trends will probably
      unfold in the next five to fifteen years.

PMID- 22616152
TI  - [Bronchoscopic treatment of emphysema].
AB  - Bronchoscopic techniques for the management of emphysema have evolved from the
      success of surgical treatment. Lung volume reduction surgery (LVRS) involves the
      removal of 20% to 30% of each lung and targets the most emphysematous segments.
      Patients with heterogeneous upper lobe emphysema and a low baseline exercise
      capacity have been identified as a subgroup within COPD in whom mortality
      benefits can even be achieved, along with improvements in exercise capacity and
      quality of life. Increased short-term mortality of approximately 5% and
      postoperative morbidity are the main limitations of LVRS. The extremely
      restrictive selection criteria for LVRS coupled with the relatively high
      mortality/morbidity have been the impetus for developing less invasive endoscopic
      modalities. Bronchoscopic lung volume reduction (BLVR) researchers have pursued
      various approaches using a range of modalities, such as blockers, stents, valves,
      sealants, and implants. BLVR appears to be safer than LVRS in terms of mortality
      and morbidity. This safety profile presents an attractive alternative for
      patients with COPD who are fragile physiologically because of the severity of
      their lung disease and the presence of co-morbid illnesses. The current report
      aims to describe the various minimally invasive modalities available for the
      treatment of emphysema.

PMID- 22616153
TI  - [What do doctors understand regarding ultrasound safety during pregnancy?].
AB  - Ultrasound has a well established record for being a safe procedure during
      pregnancy. Nevertheless, one should bear in mind the fact that ultrasound is a
      source of energy with two main bioeffects in tissue: heat and cavitation. These
      effects are inherent in the physical properties of the ultrasound transducers and
      have not been shown to be harmful to the developing fetus. The two bioeffects are
      approximated by the thermal index for heating (TI) and the mechanical index (MI)
      for cavitation effects. These indices appear clearly on the ultrasound screen,
      enabling the operator to see if their values are within the normal range. Poor
      level of knowledge regarding safety issues were found among ultrasound performers
      both in Israel and the USA. This lack of knowledge is an alarm signal for the
      health authorities, arousing a demand for the establishment of training programs
      for all ultrasound end-users.

PMID- 22616154
TI  - [Transcatheter aortic-valve implantation].
AB  - Aortic valve stenosis is associated with severe morbidity and death within
      several years of symptom onset, and its accepted treatment is surgical aortic
      valve replacement. However, many affected patients are not referred for surgery
      because of old age and significant comorbidities. In recent years, an alternative
      treatment approach has been developed, transcatheter aortic-valve implantation.
      In this review we would like to describe this treatment modality and to present
      several cases performed in our center.

PMID- 22616155
TI  - [Biphosphonate in the treatment of avascular necrosis of the femoral head].
AB  - Avascular necrosis (AVN) is a multifactorial, heterogeneous group of disorders
      that lead to a final common pathway of mechanical failure of the bone joint
      dysfunction. Pain in avascular necrosis is the result of resorption of necrotic
      bone during revascularization, before new bone has formed or consolidated enough
      for load-bearing. Biphosphonate can reduce bone resorption, thus prolonging the
      bone formation phase available, so that structural failure may be avoided. The
      aim of this study was to make a systematic review of the use of bisphosphonate in
      the treatment of AVN.

PMID- 22616156
TI  - [A prophet without honor in his own country: Dr. Ernst Wodak (1891-1962)].
AB  - Among all otolaryngologists who lived in Israel during the first half of the 20th
      century, one was most prominent - Dr. Ernst Wodak. Ernst Wodak was born in
      Czechoslovakia in 1891 and he graduated from the German University of Prague in
      1915. Dr. Wodak was a knowledgeable clinician and an outstanding researcher. He
      was mainly interested in the vestibular system, and already started to publish
      the results of his observations in 1914. In a short time Dr. Wodak became famous
      all over Europe. He was on the Editorial Boards of the Acta Oto-Laryngologica,
      and of the Excerpta Medica, and a member of the International Collegium
      Otolaryngologicum. In 1939, following the invasion of Czechoslovakia by the
      Germans, Dr. Wodak had to leave his work, and soon after he immigrated to Israel
      and settled in Tel-Aviv. For 5 years he volunteered in the ENT department in
      'Hadassah' Hospital. Even though he was already famous worldwide, Dr Wodak was
      not appreciated by most of his colleagues nor by the academic authorities. He
      could not continue his research and was forced to work only in his private clinic
      and mainly performed plastic and cosmetic operations. In spite of his
      frustration, Dr. Wodak did not lose the drive to publish and continued to
      contribute important papers to medical journals both in Israel and abroad. He
      published more than 200 papers and also wrote a few books. Dr Wodak died on
      27.4.1962 following a prolonged period of pain and suffering, away from his wife
      and daughter and abandoned by most of his friends.

PMID- 22616157
TI  - [How to write a medical book].

PMID- 22616158
TI  - [MR image registration based on an improved maximum mutual information].
AB  - Medical image registration is a key step of image processing and analysis and the
      first problem of medical image fusion to be solved. In this paper, we focus on
      magnetic resonance images registration for preoperative and postoperative of deep
      brain stimulation for the Parkinson's disease. First of all, mutual distance is
      brought into the mutual information in this paper, realize the two groups of MR
      slices (for both preoperative and postoperative) mapping, and then 3D images are
      reconstructed from the corresponding MR slices. Finally, we use Powell algorithm
      to register 3D images. After the 3D images is registered, we can analyze the
      relative position between planted electrode (postoperative) and the subthalamic
      nucleus (preoperative), and measure the quality of deep brain stimulation
      scientifically.

PMID- 22616159
TI  - [Extraction of the EEG signal feature based on echo state networks].
AB  - The performance of an electroencephalography (EEG) automatic detection and
      classification system mainly depends on the feature extraction of EEG signal.
      This paper analyses the advantages and disadvantages of the current EEG feature
      extraction methods, and then presents a new EEG feature extraction method based
      on echo state networks (ESN). The new method is a nonlinear method, and can
      extract the EEG features reversibly. Therefore, the information lost in the
      process of feature extraction is much less than that of the traditional EEG.
      Additionally, the realization of this method just needs to compute the pseudo
      inverse of a matrix, which keeps it efficient. Experimental results have showed
      that the new method could well accomplish the task of automatic detection and
      classification of EEG signals.

PMID- 22616160
TI  - [Optimization of the ray-casting algorithm based on streaming single instruction
      multiple datum extension].
AB  - At present, ray-casting algorithm is the most widely used algorithm in the field
      of medical image visualization, and it can achieve the best image quality. Due to
      large amounts of computation like sampling, gradient, lighting and blending
      calculation, the cost of ray-casting algorithm is very large. The characteristic
      of Streaming single instruction multiple datum extensions (SSE) instruction-
      supporting vector computation--can satisfy the property of ray-casting algorithm
      well. Therefore, in this paper, we improved the implementation efficient
      significantly by vectorization of gradient, lighting and blending calculation,
      and still achieved a high quality image at the same time.

PMID- 22616161
TI  - [Research on the methods for multi-class kernel CSP-based feature extraction].
AB  - To relax the presumption of strictly linear patterns in the common spatial
      patterns (CSP), we studied the kernel CSP (KCSP). A new multi-class KCSP (MKCSP)
      approach was proposed in this paper, which combines the kernel approach with
      multi-class CSP technique. In this approach, we used kernel spatial patterns for
      each class against all others, and extracted signal components specific to one
      condition from EEG data sets of multiple conditions. Then we performed
      classification using the Logistic linear classifier. Brain computer interface
      (BCI) competition III_3a was used in the experiment. Through the experiment, it
      can be proved that this approach could decompose the raw EEG singles into spatial
      patterns extracted from multi-class of single trial EEG, and could obtain good
      classification results.

PMID- 22616162
TI  - [The effect of anesthetic concentration on burst-suppression of the EEG in rats].
AB  - The term "burst-suppression" is used to describe the electroencephalogram (EEG)
      pattern characterized by theta or delta waves, at times intermixed with faster
      waves, and intervening periods of relative quiescence. Burst-suppression pattern
      can reflect the seriously suppressed brain activity under deep anesthesia. To
      investigate the relationship between burst-suppression features and anesthetic
      concentration, we adopted four straightforward indexes, i. e., burst-suppression
      ratio (BSR), burst frequency, burst amplitude and suppression amplitude, and used
      them to analyze the EEG recordings in ten isoflurane-anesthetized rats. It was
      found that all the four burst-suppression indexes changed along with anesthetic
      concentration, that BSR and burst amplitude increased with higher concentration
      of isoflurane while burst frequency and suppression amplitude decreased, and that
      BSR was the most sensitive and consistent measurement to indicate isoflurane
      concentration so it constituted a valuable tool for timely evaluation of burst
      suppression feature under deep anesthesia. The result also showed that the
      composition of carrier gas (i. e. pure oxygen vs. mixed oxygen) did not influence
      the effect of anesthesia significantly; and the four indexes of burst-suppression
      features could keep relatively stable within 60 min under the isoflurane
      concentration of 2%. The present study provides quantitative information of burst
      suppression features under different anesthetic depth and may help to develop a
      clinically satisfied system that could quantify the characteristics of EEG and
      rigorously evaluate the cerebral state of patients.

PMID- 22616163
TI  - [Study on the ReHo in treatment-naive of temporal lobe epilepsy patients with
      depressive symptoms using resting functional-MRI (fMRI)].
AB  - Epilepsy is a common neurological disease accompanied with laden economic burdens
      and heavy social resources consuming. Temporal lobe epilepsy (TLE) is an
      important subtype of the epilepsies. Our experiment was aimed to characterize the
      regional brain function alteration among the treatment na? ve TLE patients using
      ReHo. We found that elevated regional ReHo was in the left insula in the TLE
      patients, and the right one was cingulated, while the decreasing ReHo was in
      right putamen. Our result demonstrated that the key components associated with
      the epilepsy symptoms had altered the regional function in the TLE patients, and
      the disruption of cortex-thalamus-striatum loop. Our experiment provides evidence
      on the pathophysiological alteration in treatment na? ve TLE patients.

PMID- 22616164
TI  - [Decreased occipital GABA concentrations in patients with first-episode major
      depressive disorder: a magnetic resonance spectroscopy study].
AB  - Gamma amino butyric acid (GABA) is the major inhibitory neurotransmitter in the
      human brain. Alterations in GABAergic function are associated with a variety of
      neurological and psychiatric disorders. However, noninvasive in vivo measurement
      of GABA is difficult because of its low concentration and the presence of
      overlapping resonances. To study GABA concentration in the occipital cortex in
      major depressive disorder (MDD), a group of medication-naive, first episode
      depressed patients (n = 18, HAMD > 17), and a group of healthy controls (n = 23)
      were investigated using a Point Resolved Spectroscopy (MEGA-PRESS) on a 3.0 T MR
      scanner. The results showed that occipital GABA levels were significantly lower
      (P < 0.001) in the patient group than those in the healthy controls, yet the
      correlations between the severity of MDD (HAMD, BDI) and the GABA concentration
      is insignificant. Therefore, our data suggest that patients with first episode,
      unmedicated MDD have changes in cortical concentrations of GABA. This biochemical
      abnormality may be a marker of a trait vulnerability to mood disorder, and may
      explain the visual problem of severe MDD patients.

PMID- 22616165
TI  - [Verification of the accuracy of Monte Carlo-based dose calculation algorithm,
      DPM, in homogeneous and inhomogeneous tissues].
AB  - The present paper is to verify the accuracy of DPM, a Monte Carlo-based dose
      calculation algorithm, in homogeneous and inhomogeneous tissues. DPM was applied
      to calculate (1) depth dose curves and off-axis ratios at a depth of 10 cm in
      water using a 6 MeV photon beam with a 3 cm x 3 cm field and phase space file
      simulated Varian 60 degrees C medical linear accelerator with a 10 cm x 10 cm
      field at SSD = 100 (cm); (2) depth dose curves using 6 MeV photon beam in
      inhomogeneous tissues, such as water (6 cm)/lung (6 cm)/water (8 cm) with a 3 cm
      x 3 cm field and water (6 cm)/ bone (2 cm)/water (12 cm) with a 10 cm x 10 cm
      field; (3) depth dose curves using 6 MeV photon beam based on the CT data of a
      patient's head and abdomen. The doses based on DPM are compared to the doses
      calculated by DOSXYZnrc under the same condition. The error was within 3% in
      water phantom while the error was within 3% in inhomogeneous tissues, except a
      few points. It has been concluded that the DPM can accurately predict the dose to
      homogeneous and inhomogeneous tissues.

PMID- 22616166
TI  - [Research on comparison of thyroglobulin autoantibody interference in measurement
      of thyroglobulin between electrochemiluminescent assay and radioimmunoassay].
AB  - This paper is aimed to evaluatethe thyroglobulin autoantibody (TgAb) interference
      in measurement of thyroglobulin (Tg) between electrochemiluminescent assay
      (ECLIA) and radioimmunoassay (RIA). Tg and TgAb of 84 sera, including 22 Graves'
      hyperthyroidism(GD), 24 Hashimoto thyroiditis (HT) and 38 differentiated thyroid
      carcinomas (DTC), were measured by RIA and ECLIA, respectively. Recovery tests
      were carried out in 3 groups. The sera samples of the first group were added 3
      different amount of Tg calibrator; the sera samples of the second group were
      diluted 5 times, then 100 ng/ml Tg calibrator was added; the sera samples of the
      third group were divided into different subgroups depending on TgAb concentration
      with adding 100 ng/ml Tg calibrator,Tg and TgAb were measured in each dilution by
      ECLIA and RIA. Recovery rate was calculated. The Tg and TgAb values measured by
      ECLIA were correlated with that measured by RIA (r = 0.676, P = 0.000; r = 0.677,
      P = 0.000, respectively). When TgAb concentration increased, the Tg values
      decreased by ECLIA and increased by RIA. The TgAb values were decreased when sera
      were diluted, and the Tg values also reduced by RIA and increased by ECLIA. The
      added different amount of Tg calibrator had not significant influence on Tg
      recovery rates. When TgAb concentration increased, recovery rates of Tg were
      decreased by ECLIA and increased by RIA. When sera were diluted, the recovery
      rates of Tg were increased by ECLIA while decreased by RIA. RIA and ECLIA have
      good correlation with Tg measurement in 10-400 ng/ml. ECLIA has wider measuring
      range and higher sensitivity than RIA. RIA and ECLIA have good correlation with
      TgAb measurement. When TgAb is positive, Tg values are underestimated by ECLIA
      and overestimated by RIA. When sera are diluted, Tg value and the recovery rate
      are increasing by ECLIA and decreased by RIA. Recovery test can not efficiently
      rectify Tg value when TgAb is positive.

PMID- 22616167
TI  - [Studies on personalized porous titanium implant fabricated using three
      dimensional printing forming technique].
AB  - Three-dimensional printing (3DP) forming technology can shape personalized porous
      implant material with complex shape and fine structure to meet the various needs
      of different patients. In this paper, the green parts of porous titanium implants
      with diameter 25 mm x 20 mm were prepared using 3DP, and then debinded at 500
      degrees C under vacuum. Finally they were sintered in the argon gas at 1 300
      degrees C. The pore sizes were observed, and they were between 50-150 microm
      under SEM. The results of porosity, bulk density, Vickers hardness, compressive
      strength and elastic modulus were (44.26% +/- 2.43)%, (2.59 +/- 0.81)g/cm3, 134.2
      151.6 (61.2 +/- 3.2) MPa, (3.25 +/- 1.08) GPa, respectively. That shows excellent
      biomechanical compatibility. It is concluded that 3DP has wide application for
      fabrication of personalized porous titanium implant.

PMID- 22616168
TI  - [Establishment and application of subject-specific three-dimensional finite
      element mesh model for osteonecrosis of femoral head].
AB  - This paper is aimed to acquire high Geometric similar Subject-specific three
      dimensional (3D) finite element mesh model of hip joint containing necrotic
      femoral head according to individual patient's X-ray, CT and MRI by using the
      image registration and fusion technology. We selected a middle-aged female
      patient with osteonecrosis of femoral head, obtained the X-ray, CT and MRI images
      respectively. Then we established 3D solid model separately based on these image
      data by using Mimics 13. 1 and Pro/E 5.1 software. We confirmed the match points
      and then proceed the 2D image registration after image projection conversion.
      Finally we showed the 3D finite element mesh model. A highly geometric similar
      subject-specific 3D finite element mesh model for osteonecrosis of femoral head
      has been established, which included normal cortical bone, cancellous bone,
      articular cartilage and necrotic zone, fractured trabecular bone within the
      femoral head. The model truly reflects the morphological characteristics and
      relationship of hip joint with osteonecrosis of femoral head, provides a
      relatively ideal research platform for further biomechanical analysis and
      surgical simulation.

PMID- 22616170
TI  - [Segmentation and cavity filling of color image from stained trabecular sections
      based on HSV space].
AB  - A approach to segment the color image based on Hue-Saturation-Value (HSV) space
      was proposed, and it was used to segment the color image digitized from the bone
      sections stained with Masson-Goldner's Trichrome by CCD camera. According to HSV
      approach, color image was transformed from RGB space to HSV space at first, and
      then the image was segmented by using the threshold value of hue (90 < H < 150)
      and saturation (S > 0.25) to find the image of the green color stained
      trabecular. And then used the threshold value of saturation (S < 0.2) and value
      (V > V(background) x 0.95) to find the unstained high brightness field. At last,
      unstained high brightness fields which were concluded in stained trabecular image
      were filled with the color of trabecular, so the completely trabecular image
      could be drawn. The results showed that HSV approach was fast and simple, and it
      could be an efficient automatic algorithm.

PMID- 22616169
TI  - [Preliminary study on simulating sensory nerves of intestinal contents using
      ultrasound detecting system].
AB  - Successful assessing intestinal lumen content with ultrasound signals might lay a
      strong basis for the development of the artificial anal sphincter. In the present
      study, we utilized a modified MLU02-212 ultrasonic gas bubble detector to test
      the distal part of proximal colon in each rabbit, for the group of twenty healthy
      New Zealand rabbits. Voltage signals of solid, liquid, gas and empty content of
      the lumen were collected and compared. The results indicated that there were
      significant differences among the voltage signals in the 4 conditions (P =
      0.000), respectively. Multiple comparison showed significant differences existed
      in any pair of the four conditions (P = 0.000). Three signal non-overlapping
      regions existed in these 4 conditions. Thus it seemed that ultrasound could be
      utilized to distinguish various contents inside the intestinal lumen and could
      act as "artificial sensory nerve".

PMID- 22616171
TI  - [Production and law of variation of the pleural cavity intrinsic pressure and the
      pressure of alveolar wall during respiratory process].
AB  - All physiologic textbooks deal with pleural cavity pressure, alveolar wall
      pressure and pressure inside the lung, but they have not stated these ideas
      clearly. The present study reveals production and Law of variation of the
      intrinsic pressure of pleural cavity, the pressure of alveolar wall and the
      intrinsic pressure in the alveoli. Pleural cavity intrinsic pressure is produced
      by the pressure from pleura expanding or compressing force of the lungs. When the
      lungs calmly inhale, the thorax expands, pleural cavity negative pressure
      increase. When the lungs calmly exhale, thorax reduces, but thorax and lungs are
      still in the extended state, pleural cavity is still in negative pressure. With
      thorax reducing, negative pressure decreases. When the lungs are at the forced
      expiration, the lung pleura and wall pleura extrude pleural cavity, only to
      produce positive pressure. The pressure of alveolar wall is the algebraic sum of
      the intrinsic pressure of pleural cavity, the intrinsic pressure of pulmonary
      tissue and the additional pressure of alveolar wall. We did the calculation of
      additional pressure on the alveolar wall by using Laplace formula of spherical
      elastic membrane. The intrinsic pressure of alveoli depends on the moving speed
      or slowness of expansion or compression of alveolar wall and the size of trachea
      resistance.

PMID- 22616172
TI  - [The application value of dual-source CT in the preoperative evaluation of living
      donor kidneys].
AB  - This study was to evaluate the value of dual-source CT in the preoperative
      assessment of living donor kidneys. We collected fifty-five consecutive living
      kidney donors (male 35, female 20, average age, 39 years old), and performed dual
      source CT scan. The plain scan, pre-enhanced arterial phase and venous phase
      examinations were performed, with the scan level ranged from the 11th thoracic
      vertebral body to the iliac crest. All the basic images were reconstructed using
      volume rendering(VR), maximum intensity projection (MIP), multi-planar
      reconstruction (MPR) techniques to evaluate the anatomical location and variation
      of renal arteries and veins, and the morphology and function of kidney and
      urinary tract. All the 55 cases were successful, with completion of CT scan and
      clear images. 46 cases among the all cases had normal renal arteries and veins,
      while 6 cases had accessory arteries, 2 cases had pre-hilar renal artery
      branching, and 1 case had vein variation. For the renal parenchymas, 48 cases
      were normal, while 2 cases had angiomyolipoma and 5 cases had cortical cyst.
      There were no variation and disease in upper urinary tract. Compared with the
      surgical findings, the diagnostic accuracy was 100% with dual-source CT. In
      conclusion, the dual-source CT can accurately evaluate the vessel of kidney,
      renal parenchyma and upper urinary tract of living renal donors, can provide
      reliable imaging information for screening of living donor kidney and can help
      make operation program in living kidney transplantation.

PMID- 22616173
TI  - [Studies on the ERP underlying premeditated and temporary deception].
AB  - The event-related potential (ERP) P300 was recorded to analyze the temporal
      sequences character and the P300 compositions in premeditated and temporary
      deception. When 15 healthy undergraduates watched the stolen, familiar but not
      stolen and strange object pictures, the reaction time was recorded and EEG data
      were collected to analyze the amplitudes of N1, N2 and P3 sub-component of P300
      in honesty and deception group respectively through analog theft paradigm. The
      results showed that the amplitudes of N1, N2 and P3 in premeditated deception
      group were markedly larger than those in temporary deception, and the reaction
      time of deception group was longer than that of honesty group. Compared with
      temporary deception, more attention resources were invested and intensely
      response conflict was induced by premeditated deception.

PMID- 22616174
TI  - [Preliminary research into the relation between characteristic parameters of
      transesophageal photoelectric pulse wave in descending aorta and ambulatory
      artery blood pressure].
AB  - The present paper aims to investigate the relation between characteristic
      parameters of transesophageal photoelectric pulse wave in descending aorta and
      ambulatory artery blood pressure. The chests of ten adult experimental dogs were
      performed to take the photoelectric pulse wave of descending aorta
      transesophageally. The concurrent femoral artery invasive blood pressure was
      recorded simultaneously. Stepwise regression analysis method was used to study
      the correlation efficient between characteristic parameters of descending aorta
      pulse wave (H, h, h/H, g/H, At, s, H(1 + ts/td), k)and invasive artery blood
      pressure. The characteristic parameters, k and h/H (ratio: 90% and 80%) was
      proved that they had good correlation with systolic pressure; and k, H and s
      (ratio: 90%, 80% and 70%), had good correlation with diastolic pressure; while k
      and H (ratio: 90% for both) had good correlation with mean pressure. The mean
      values of multiple correlation coefficients of the selected characteristic
      parameters of descending aorta pulse wave with systolic pressure, diastolic
      pressure and mean pressure of femoral artery were 0.871, 0.900 and 0.856,
      respectively. The characteristic parameters of descending aorta pulse wave had
      specific correlation with systolic pressure, diastolic pressure and mean
      pressure.

PMID- 22616175
TI  - [The source and influential factors in signals of trans-esophageal oxygen
      saturation].
AB  - This paper is aimed to investigate the signal source and influential factors in
      signals of trans-esophageal pulse oxygen saturation (SeO2). The red light of the
      SeO2 probe was faced directly to the descending aorta (DA) of the mongrel dogs.
      The readings and waveform of SeO2 signals were recorded under following
      conditions: before and after DA was shield; before and after the blood supply of
      esophagus was cut off; under the different touch pressures between the SeO2 probe
      and the esophageal wall. The readings and waveform of SeO2 signals were also
      recorded respectively at both different esophageal depth and directions when
      mechanical ventilation was on and off. The tongue oxygen saturation (StO2) was
      recorded simultaneously as control. The waveform of SeO2 signals disappeared
      after DA was shield (P < 0.001). No significant difference was found in the SeO2
      signals before and after the blood supply of esophagus was cut off (P > 0.05).
      Compared with the StO2 readings when the SeO2 probe was placed at different
      esophageal depth, the waldeyer ring, cervical area and thoracic inlet,the
      readings of SeOz significantly decreased (P < 0.05) while mechanical ventilation
      was on and off. However, there was no significant difference in the readings
      between SeO2 signals from DA, aortic arch (AA) and left subclavian artery and the
      StO2 signals recorded simultaneously. Mechanical ventilation had a remarkable
      effect on the SeO2 signals at different esophageal depth (P < 0.05), but the StO2
      signals lay in its insensitivity to its influence. The readings of StO2 signals
      were significantly different from that of StO2 signals when the touch pressure
      between the SeO2 probe and the esophageal wall below 40 mmHg (P < 0.01). The
      directions of the optimum SeO2 signals acquired at different esophageal depth
      were not the same. The SeO2 signals were primarily derived from deeper arteries
      around the esophagus. All of Mechanical ventilation, location of the SeO2 probe
      in the esophagus and the touch pressure between the probe and esophageal wall can
      influence SeO2 signals.

PMID- 22616176
TI  - [Effects of electrode on epileptogenic focus potential and expressions of the
      beta subunit of ATP synthase in rats with penicillin-induced epilepsy].
AB  - The changed process of bioenergy and the effects of electrode interfering on
      penicillin-induced epileptic brains in epileptic seizures rats were investigated.
      Fifty Sprague-Dawley (SD) rats were randomly divided into 4 groups, i. e. normal
      saline control group (group A), penicillin model group (group B), metal electrode
      interfere group (group C) and insulated electrode interfere group (group D). The
      epileptogenic potential and the expressions of the beta subunit of-ATP synthase(
      ATP5B) in hippocampal neurons were measured. The epileptogenic foucus potential
      and expressions of ATP5B in hippocampus neurons showed that the trend increased
      at first and decreased implantation of later, and the implantation of metal
      electrodes decreased the epileptogenic foucus potential at corresponding time
      point, but had no effect on the expressions of ATP5B. The change of epileptogenic
      focus potential was reduced by implantation of metal electrode, possibly due to
      the alteration of corrosponding bioenergy metabolism which had participated in
      the process of epileptic seizure.

PMID- 22616177
TI  - [Effect of pulsed electromagnetic field with different frequencies on the
      proliferation, apoptosis and migration of human ovarian cancer cells].
AB  - Pulsed electromagnetic field (PEMF), a non-invasive physical treatment modality,
      is now used clinically to promote bone formation for osteoporosis. The patients
      after ectomy of ovarian cancer are easily complicated with osteoporosis. However,
      the safety parameters of PEMF treatment for the osteoporosis patients after
      resection of ovarian cancer remain unknown. Therefore, this study was designed to
      examine the effect of different frequency of PEMF on the proliferation, apoptosis
      and migration of human ovarian cancer cells (SKOV3 cells). Cultured SKOV3 cells
      were exposed to PEMF stimulation daily with radiation of 8 Hz, 16 Hz, 32 Hz and
      64 Hz, respectively. We used sinusoidal waves with strength of 1 mT, twice a day
      with an interval of 12 hours. An exposure to the waves lasted 30 minutes, for 3
      days, with those no PEMF stimulation serving as the control. The proliferation of
      cells was detected using EdU assay, and the apoptosis of cell was assessed with
      Annexin V-FITC fluorescence. The migration of cells was measured with the scratch
      wound assay. The data showed that exposure to PEMF of 1 mT, 8 Hz for 3 days could
      significantly inhibit the proliferation of SKOV3 cells and induce the apoptosis
      of the cells. The migrated distance and number were increased by 1 mT, 8 Hz or 32
      Hz PEMF stimulation, but decreased by 1 mT, 16 Hz treatment. The results
      suggested that we should be careful about the safety of PEMF treatment and
      strictly choose the optical parameters in preventing or treating the osteoporosis
      of the patients after resection of ovarian cancer.

PMID- 22616178
TI  - [Effect of the composition and structure of the drug delivery device on the drug
      release rate].
AB  - To investigate the effects of the property of drugs and the structure of drug
      delivery devices on the drug release rate, the effects of sealing methods,
      length, thickness and drug-loading manner of the silicone tubes on the drug
      release rate were examined using progestin, testosterone, estradiol as the
      delivery drugs. The results showed that the property of the drug was the crucial
      factor to the drug release rate. The sealing methods, length, thickness and drug
      status of the silicone tubes had significant effects on the drug release rate and
      the effects were closely related to the property of the drugs. In addition, our
      newly developed glass-silicone tube has larger drug deposition capability and
      smaller drug release area, offers an effective and convenient method for the
      sustained drug delivery with quick release traits in vivo.

PMID- 22616179
TI  - [Three methods with functions of modification on aluminum borate whisker and with
      influence on flexural properties of dental composite resins].
AB  - The present paper is aimed to discuss the influence of three different ways on
      modification of aluminum borate whiskers (AlBw) and on flexural properties of
      dental composite resins. In Group A, AlBw and silicon dioxide (SiO2)
      nanoparticles were thermally fused directly under certain processes. In Group B,
      Si-O network was formed on the surface of AlBw via the sol-gel process of
      tetraethoxysilane, then thermally fused with SiO2 nanoparticles to form AlBw-SiO2
      compound as inorganic fillers. In Group C, SiO2 nanoparticles were repaired by
      sol-gel method of tetraethoxysilane under certain processes, and were deposited
      in the surface of AlBw. The mixtures were fused with high temperature sintering
      method. The effects of the surface morphology of AlBw with different ways were
      characterized by TEM and SEM. Then the mixtures were polymerized with resin
      matrix after surface siliconization and their flexural strength and Young's
      modulus were determined. SEM was used to examine specimen fracture surfaces. The
      results showed that the flexural properties of dental composite resins were
      significantly improved after whiskers were modified. Different methods produce
      different effects. Flexural strength of the Group A is (95.28 +/- 4.53) MPa. The
      results of TEM and SEM revealed that the aggregation was obvious between AlBw and
      SiO2 nanoparticles. Flexural strength of the Group B was (123.14 +/- 17.37) MPa.
      The results of TEM and SEM revealed that the dispersity was improved but SiO2
      nanoparticles also reunited. AlBw were modified with nanometer-size SiO2
      particles which were prepared by sol-gel method based on tetraethyl orthosioate
      (TEOS), the flexural properties of a new type of dental composite resins was
      (130.29 +/- 8.38) MPa. The results of TEM and SEM revealed that better dispersion
      between AlBw and SiO2 nanoparticles occurred. The SiO2 nanoparticles were fused
      and attached onto the surface of AlBw uniformly.

PMID- 22616180
TI  - [In vitro biologic evaluation on nano-hydroxyapatite/poly (L-lactic acid)
      biocomposites fabricated using in-situ growth method].
AB  - The aim of this research was to estimate the bioactivity of nano
      hydroxyapatite/poly (L-lactic acid) composites in simulated body fluid. In vitro
      test showed that the pH value of simulated body fluid (SBF) declined gradually
      and the existence of hydroxyapatite (HA) particles neutralized the acid
      degradation product of poly (L-lactic acid) (PLLA). Bone-like apatite deposited
      on the surface, and silkworm-like crystals and plate-like clusters appeared after
      soaking. At the same time, there were many honeycomb-like pores caused by nano
      composite degraded. The results indicated that the hydroxyapatite/poly (L-lactic
      acid) nano-composites have good bioactivity and degradation characteristics.

PMID- 22616181
TI  - [Bioequivalence research of cyclosporin soft capsules].
AB  - This paper is aimed to study the bioavailability and bioequivalence of
      Cyclosporin Soft Capsules (test preparation and reference preparation) in Chinese
      healthy volunteers. A high performance liquid chromatography-ultraviolet (HPLC
      UV) method for determining the concentration of Cyclosporin A in human whole
      blood was developed and methodological validated. In accordance with the
      randomized two-period self crossover study, 24 volunteers received a single oral
      dose of 400 mg of test preparation or reference preparation. Multiple blood
      samples were collected post dose and then the concentration of Cyclosporin A in
      human whole blood samples was determined using the validated assay. The
      pharmacokinetic parameters including AUC0-t, Cmax, Tmax, and T1/2 were calculated
      using the non-compartmental method. The bioequivalence of the two preparations
      was evaluated. After receiving single dose of 400 mg of Cyclosporine A, the
      pharmacokinetic parameters of T1/2, Cmax, Tmax, and AUC0-t, of Cyclosporin A were
      (10.114 +/- 6.329) h and (9.717 +/- 4.076) h, (2021.235 +/- 298.581) ng x ml(-1)
      and (1992.192 +/- 1286.923) ng x ml(-1) (1.729 +/- 0.361) h and (1.813 +/- 0.323)
      h, (9824.811 +/- 1633.026) ng x h x ml(-1) and (10316.514 +/- 1395.955) ng x h x
      ml(-1) for test preparation and reference preparation, respectively. The
      statistical results suggested that these parameters were comparable between the
      two preparations. The results showed that the test preparation was bioequivalent
      with the reference preparation in healthy volunteers.

PMID- 22616182
TI  - [The preparation and evaluation of tissue inducible nerve guide conduit].
AB  - The objective of this research was to fabricate a novel tissue inducible nerve
      guide conduit, and to evaluate its biologic property. The microspheres were
      prepared with chitosan that encapsulated ligustrazine. The drug release of the
      chitosan microspheres was detected with application of the controlled release
      method in vitro. Chitosan microspheres were mixed with collagen to fabricate the
      tissue inducible nerve conduit, which were crosslinked with 2% genipin for 24h.
      Mechanical properties of the nerve guide conduit samples, including maximum load
      and breaking load, were measured using an Instron Series IX Automated Materials
      Testing System. The flexibility of the nerve guide conduit was determined with
      the texture evaluation instrument. Different methods, such as scanning electron
      microscope (SEM), light microscope (LMS) and immunofluorescence were used to
      analyze the spatial structure of the nerve guide conduit, the distribution of the
      microspheres, the state of the nerve duct combined with mesenchymal stem cells
      (MSCs), and the effect of the ligustrazine that released from chitosan
      microsphere on MSCs differentiation into nerve cells, respectively. The results
      showed that the chitosan microspheres had better releasing effect. The mechanical
      properties resultant nerve guide conduit were determined. The maximum load and
      breaking load of the genipin crosslinked samples were significantly higher than
      that observed with the non-crosslinkers, increasing to (0.76 +/- 0.15) N and
      (0.69 +/- 0.17) N from (0.23 +/- 0.09) N and (0.20 +/- 0.12) N for the non
      crosslinkers (P < 0.01). The degradation rates of non-crosslinked and crosslinked
      by genipin were(58.62 +/- 7.59) mg and (9.23 +/- 2.47) mg, respec- tively. This
      had a statistical significance (P < 0.01). The average linearities in dry and
      hygrometric state of the nerve guide conduit were (0.597 +/- 0.012) LC and (0.333
      +/- 0.015) LC, respectively, which also had statistical significance (P < 0.01).
      The flexibility in the hygrometric state of the nerve guide conduit was better
      than that of the dry. SEM analysis of the samples demonstrated that the
      structures of the nerve guide conduit were significantly changed in crosslinking
      samples, the microspheres were uniformly distributed on the surface of scaffold,
      the ligustrazine that released from the chitosan microspheres could promote MSCs
      to express NSE and MAP2 that were the relevant marker molecule of nerve cells.
      The nerve guide conduit is combined with MSCs, which promote MSCs proliferation
      and NSE expression by the ligustrazine that released from the chitosan
      microspheres. The conduit has better biological compatibility and tissue
      inducible function.

PMID- 22616183
TI  - [Increased oxidative damages of erythrocytes caused by declined blood oxygen
      saturation].
AB  - This paper was to explore the effect of blood oxygen saturation (SO2) on
      oxidative damages of erythrocytes under the condition of oxidative stress.
      Keeping SO2 of cultured erythrocytes in vitro at the states of 0.3, 0.5, 0.7, 0.9
      and 0.98, respectively, we induced oxidative stress by tert-buthylhydroperoxide
      (BHP, 0.15 mmol/L of final concentration). After incubation, antioxidant capacity
      was assessed by measuring content of reduced glutathin hormone (GSH) in
      erythrocytes. Methemoglobin (MetHb) content, lipid peroxidation (thiobarbituric
      acid-reactive substances, TBARS) and denatured globin-chains on the plasma
      membrane were measured to assess the extent of oxidative damages. The results
      showed that in the presence of BHP, GSH contents increased from 0.3 to 0.98
      groups; MetHb, TBARS and globin-chains levels all dropped with the rise of SO2.
      In conclusion, antioxidant capacity and oxidative damages of erythrocytes are
      closely related to SO2, declined SO2 could promote oxidative damages of
      erythrocytes.

PMID- 22616184
TI  - [Study on genetic transformation of antigen G3VP7 gene of human rotavirus in
      peanut].
AB  - In order to increase the expression level of target gene and to simplify the
      purifying process of separation and purification, we performed the transgenetic
      research of antigen VP7 gene into peanut via Agrobacterium tumefaciens. The plant
      binary expression vector is pBOG3VP7 harboring fusion gene oleosin-vp7, which is
      promoted by ole-promoter. Cotyledon nodes were used as transformation recipients.
      Transformed individuals were obtained through selection on medium containing 125
      mg L-1 Kan. Integration of transgenes was assessed by PCR amplification and PCR
      Southern blot hybridization. Taking pBOG3VP7 plasmid as positive control, non
      transformed peanut as negative control. 6 plants among 11 plants grown up through
      seletion medium were detected by PCR and the rate of positive plants is 54.5%.
      PCR positive plants were further analysed by PCR-Southern blot hybridization. The
      results showed that 3 plants have DNA bloting bands. The results also showed that
      the foreign gene was integrated into genome of transformed peanuts. Elevated
      expression of rotavirus VP7 antigen in transgenic peanuts was a critical factor
      in the development of efficient and cheap plant oral vaccine.

PMID- 22616185
TI  - [Ultrasound image de-noising based on nonlinear diffusion of complex wavelet
      transform].
AB  - Ultrasound images are easily corrupted by speckle noise, which limits its further
      application in medical diagnoses. An image de-noising method combining dual-tree
      complex wavelet transform (DT-CWT) with nonlinear diffusion is proposed in this
      paper. Firstly, an image is decomposed by DT-CWT. Then adaptive-contrast-factor
      diffusion and total variation diffusion are applied to high-frequency component
      and low-frequency component, respectively. Finally the image is synthesized. The
      experimental results are given. The comparisons of the image de-noising results
      are made with those of the image de-noising methods based on the combination of
      wavelet shrinkage with total variation diffusion, the combination of
      wavelet/multiwavelet with nonlinear diffusion. It is shown that the proposed
      image de-noising method based on DT-CWT and nonlinear diffusion can obtain
      superior results. It can both remove speckle noise and preserve the original
      edges and textural features more efficiently.

PMID- 22616187
TI  - [Image segmentation in tumor CT based on the improved C-V model].
AB  - Aiming at the shortcomings of slow convergence and inaccuracy segmentation in non
      homogeneous images, improvements were made on the traditional C-V model in two
      aspects. Firstly, using a novel model based on local gradient, the initial
      contour of the C-V model was quickly moved near the target border, greatly
      reducing the evolution time. Secondly, combining the characteristics of GVF model
      from two directions to the target border, an adaptive velocity reconciling item
      was added for velocity equation of the C-V model to make the model converge to
      the true border. The segmentation experiments for liver tumors in CT showed that
      the proposed method could be effective.

PMID- 22616186
TI  - [Instantaneous energy spectrum analysis for frequency following response of
      speech evoked brainstem response].
AB  - Speech evoked brainstem responses (s-ABRs) elicited by a speech syllable /da/ are
      composed of four parts: onset response (OR), transitional response, frequency
      following response (FFR) and offset response. FFR elicited by periodic events
      behaves like a quasi-periodic waveform corresponding to the stimulus sounds. The
      fast Fourier transform based spectra are commonly used to exam the
      characteristics of s-ABR in practice, which is, however, unable to trace the
      occurrence of the main components of s-ABR. The FFR is usually not obvious in the
      original individual s-ABR waveform. In this paper, we proposed a novel approach
      to observe the FFR by an instantaneous energy spectrum performed on the intrinsic
      mode functions (IMFs) after empirical mode decomposition (EMD) of the s-ABR. We
      demonstrated that the FFR is most pronounced on the second layer of IMFs. This
      finding suggests a new way which may be available to characterize and to detect
      the FFR better. This will benefit the clinic applications of s-ABRs.

PMID- 22616188
TI  - [Infrared video-nystagmograph tracing].
AB  - As the infrared image gray distribution of nystagmus video is uneven, the
      accuracy of pupil edge detection could not be high enough. A pupil location
      method based on morphology and Canny algorithm was presented in this paper. Some
      meaningless regions were removed by morphology, and target was smoothed. The
      connected regions were separated, and the largest connected region-pupil was
      found. Then the pupil edges were extracted by the designed Canny edge detection
      algorithm. The coordinates of pupil for each frame images were calculated and the
      pupil movement tracking was fitted. Finally, desired clinical diagnostic
      information would be obtained from the tracking. Experimental results showed that
      the method could be adapted to different gray values for different objects, and
      could accurately detect the edge of the pupil. As the pupil was tracked well, the
      experimental results could reflect the eye movement. The method provides a
      practical way for the pupil location of existing domestic researches in video
      nystagmograph.

PMID- 22616190
TI  - [Continuous wavelet analysis of heart rate variability during general
      anesthesia].
AB  - The depth of anesthesia can be assessed by means of analyzing heart rate
      variability (HRV). Continuous wavelet transform (CWT) was used to obtain more
      accurate results on the changes of low frequency (LF) and high frequency (HF)
      components of HRV signals (RR interval sequences) before and after general
      anesthesia. With wavelet scale transformed into frequency, the obtained time
      frequency energy distributions showed that the LF and HF components of HRV
      signals were suppressed after general anesthesia, while the LF/HF ratio reduced
      from 9.0219 to 3.5573. The time-frequency distribution showed that CWT can more
      accurately locate the abrupt changes in time-domain, giving more precise range of
      frequency changing, compared with traditional time-frequency analysis method. The
      results indicated that, as a new time-frequency analysis method of analyzing HRV
      during general anesthesia, CWT provides more accurate time-frequency location,
      and consequently, offers more accurate monitoring results of anesthesia depth.

PMID- 22616189
TI  - [A tracking algorithm for live mitochondria in fluorescent microscopy images].
AB  - Quantitative analysis of biological image data generally involves the detection
      of many pixel spots. In live mitochondria video image, for which fluorescent
      microscopy is often used, the signal-to-noise ratio (SNR) can be extremely low,
      making the detection and tracking of mitochondria particle difficult. It is
      especially not easy to get the movement curve when the movement of the
      mitochondria involves its self-move and the motion caused by the neuron. An
      tracking algorithm for live mitochondria is proposed in this paper. First the
      whole image sequence is frame-to-frame registered, in which the edge corners are
      chosen to be the feature points. Then the mitochondria particles are tracked by
      frame-to-frame displacement vector. The algorithm proposed has been applied to
      the dynamic image sequence including neuron and mitochondria, saving time without
      manually picking up the feature points. It provides an new method and reference
      for medical image processing and biotechnological research.

PMID- 22616191
TI  - [Research on an in vivo near-infrared real-time monitoring system and its
      application in pharmacokinetics].
AB  - The real-time in vivo measurement method has been urgently needed in the research
      of pharmacokinetics. In the present paper a new in vivo detection method based on
      fluorescence spectroscopy has been proposed and the monitoring system has been
      built which is used for pharmacokinetics studies in rats. The relationship
      between fluorescence intensity and concentration was obtained. By detecting the
      fluorescent dye Cypate in real-time in rats, the properties of the system have
      been validated by comparing with the fluorescence imaging system in vitro. The
      results showed that the system could be feasible for: (1) The linear regression
      equation of Cypate concentration in the range of 0.098-25 microg/ml is y =
      73.249x + 130.97 (R2 = 0.9991 and P < 0.001). RSD of high, medium and low
      concentration is 1.23%, 6.29% and 13.48%, respectively, and the detecting
      sensitivity is 0.0981 g/ml; (2) The fluorescent dye concentration from the system
      is consistent (r = 0.9925) with the fluorescence imaging system in vitro. The
      fluorescent dye metabolism in rats can be well detected. It can be concluded that
      a new real-time in vivo detecting method in the paper can be used in
      pharmacokinetics research.

PMID- 22616193
TI  - [Progress in data mining techniques of diagnosis of breast cancer].
AB  - Data mining is to extract the interested information or knowledge from large
      databases using a series of techniques. The information and knowledge are
      generally hidden, unknown, but potentially useful, which can be expressed as
      concepts, rules, laws, modes or other forms. This article introduces the
      background and concepts of data mining, and reviews its application in medicine
      and the diagnosis of breast cancer for the most recent years. We also discuss the
      significance and current problems of this application in the diagnosis of breast
      cancer.

PMID- 22616194
TI  - [Exploration of the design of media access control layer of wireless body area
      network for medical healthcare].
AB  - This paper proposes a media access control (MAC) layer design for wireless body
      area network (WBAN) systems. WBAN is a technology that targets for wireless
      networking of wearable and implantable body sensors which monitor vital body
      signs, such as heart-rate, body temperature, blood pressure, etc. It has been
      receiving attentions from international organizations, e. g. the Institute of
      Electrical and Electronics Engineers (IEEE), due to its capability of providing
      efficient healthcare services and clinical management. This paper reviews the
      standardization procedure of WBAN and summarizes the challenge of the MAC layer
      design. It also discusses the methods of improving power consumption performance,
      which is one of the major issues of WBAN systems.

PMID- 22616192
TI  - [Spinal injury: multidetector computed tomography features and mechanism].
AB  - As one of the severe injuries, spinal injury is common in major blunt trauma and
      a spinal cord injury can make the patient be disabled or life-threatened with
      poor long-term physical and psychological consequences. The treatment of spinal
      injuries is a significant proportion of all the workload of trauma management
      based on the neurologic defect, spinal column instability, and the compression of
      spinal cord. Multidetector computed tomography (MDCT) is the better examination
      than conventional radiography in depicting the type of injuries, spinal column
      instability, spinal canal narrowing degree and neurologic defect, and can be
      performed alone in patients sustaining severe trauma. The purpose of this review
      is to evaluate the MDCT features of this types of injuries based on the
      mechanism.

PMID- 22616195
TI  - [Progress with research on the permeability characteristics of reproductive cell
      membranes].
AB  - The successful cryopreservation of reproductive cells has important practical
      significance in many fields. In order to improve the recovery rate and viability
      of cryopreserved cells, it is necessary to study the permeability characteristics
      of cell membrane to both water and cryoprotectant. In this paper we review the
      studies on membrane permeability of animal reproductive cell for the recent
      years. We firstly list the typical permeability data of spermatozoa and oocyte
      membrane for water and cryoprotectant. We then analyze the effects of these
      characteristics on the design of cryopreservation protocol. We also introduce the
      latest experimental methods to measure the cell membrane permeability.

PMID- 22616196
TI  - [Roles of matrix metalloproteinase in migration and differentiation of bone
      marrow-derived mesenchymal stem cells].
AB  - Matrix metalloproteinases (MMPs) are endocellular proteolytic enzymes. They are
      so named because they need Ca2+, Zn2+ and other metal ions as their cofactors.
      MMPs play an important biological role in regulating the formation, remodeling
      and degradation of extracellular matrix and participate in various physiological
      and pathological processes of cells. Bone marrow-derived mesenchymal stem cells
      (BMSCs) are a kind of pluripotent stem cell which has the ability to self-renew
      and differentiate into functional cells. Meanwhile, they can respond to the
      damage signals and migrate to injured site for tissue repair and regeneration.
      MMPs and their inhibitors TIMPs affect the differentiation and migration of
      BMSCs. This article reviews the roles of MMPs in differentiation and migration of
      BMSCs.

PMID- 22616197
TI  - [Progress in research on molecular biology and application in dominant antigens
      ESAT6 and CFP10 of TB vaccine].
AB  - As the dominant antigens, early secreted antigenic target 6 (ESAT6, E6) and
      culture filtrate protein 10 (CFP10, C10) had once been the focus of tuberculosis
      (TB) vaccine due to their capability of inducing strong cell immune response in
      the host. They are also endowed with promising future of prevention against and
      diagnosis of TB. In this review, we systematically introduce recent research
      progress of E6 and C10, especially in structure-function, biological
      characteristics, protein expression and secretion, host immunity and vaccine
      development, and the prospects of their application are also discussed.

PMID- 22616200
TI  - Deletion of exon 26 of the dystrophin gene is associated with a mild Becker
      muscular dystrophy phenotype.
AB  - With the possible introduction of exon skipping therapy in Duchenne muscular
      dystrophy, it has become increasingly important to know the role of each exon of
      the dystrophin gene to protein expression, and thus the phenotype. In this
      report, we present two related men with an unusually mild BMD associated with an
      exon 26 deletion. The proband, a 23-year-old man, had slightly delayed motor
      milestones, walking 1 1/2 years old. He had no complaints of muscle weakness, but
      had muscle pain. Clinical examination revealed no muscle wasting or loss of
      power, but his CK was 1500-7000 U/l. Muscle biopsy showed dystrophic changes. He
      had comorbidity with dystonia, slight mental retardation, low stature and
      neuropathy. The brother of the proband's mother came to medical attention when he
      was 43 years old. He complained about muscle pain. On examination, a MRC grade 4+
      hip extention palsy and a discrete calf hypertrophy was noted. Creatine kinase
      was normal or raised maximally to 500 U/l. The muscle biopsy was myopathic with
      increased fiber size variation and many internal nuclei, but no dystrophy. No
      comorbidity was found. In both cases, western blot showed a reduced dystrophin
      band. Genetic evaluation revealed a deletion of exon 26 of the dystrophin gene in
      both. This is the first description of patients with a exon 26 deletion of the
      dystrophin gene. Assuming the proband's comorbidity is unrelated, exon 26
      deletion results in a very mild phenotype. This might be of interest in planning
      exon skipping therapy for Duchenne muscular dystrophy. This report also shows
      that BMD may present with a normal CK.

PMID- 22616199
TI  - Genetic counseling in Pompe disease.
AB  - Pompe disease is caused by glycogen accumulation due to a deficiency of the
      lysosomal acid alpha-glucosidase enzyme by which it is degraded. It is a rare
      disease, accounting for 1:40.000 births. It is inherited as an autosomal
      recessive trait so that a couple presents a recurrent risk of 25% to have a child
      affected, at each pregnancy. The diagnosis could be achieved by biochemical
      and/or molecular testing. Carrier detection and prenatal diagnosis are available
      when the molecular defect is known.

PMID- 22616198
TI  - Cardiac involvement in patients with spinal muscular atrophies.
AB  - The spinal muscular atrophies (SMAs) include a group of disorders characterized
      by progressive weakness of the lower motor neurons. Several types of SMAs have
      been described based on age onset of clinical features: Acute infantile (SMA type
      I), chronic infantile (SMA type II), chronic juvenile (SMA type III), and adult
      onset (SMA type IV) forms. The incidence is about 1:6,000 live births with a
      carrier frequency of 1:40 for the severe form and 1:80 for the juvenile form. The
      mortality and/or morbidity rates of SMAs are inversely correlated with the age at
      onset. SMAs are believed to only affect skeletal muscles; however, new data on
      SMA mice models suggest they may also impact the heart. Aim of the study was to
      retrospectively examine the cardiological records of 37 type molecularly
      confirmed II/III SMA patients, aged 6 to 65 years, in order to evaluate the onset
      and evolution of the cardiac involvement in these disorders. All patients had a
      standard ECG and a routine echocardiography. The parameters analysed were the
      following: Heart rate (HR), PQ interval, PQ segment, Cardiomyopathic Index (ratio
      QT/PQs), ventricular and supraventricular ectopic beats, pauses > or = 2,5 msec,
      ventricle diameters, wall and septum thickness, ejection fraction, fiber
      shortening. The results showed that HR and the other ECG parameters were within
      the normal limits except for the Cardiomyopathic Index that was higher than the
      normal values (2,6-4,2) in 2 patients. Left ventricular systolic function was
      within the normal limits in all patients. A dilation of the left ventricle
      without systolic dysfunction was observed in only 2 patients, aged respectively
      65 and 63 years; however they were hypertensive and/or affected by coronary
      artery disease. Data here reported contribute to reassure patients and their
      clinicians that type II/III SMAs do not present heart dysfunction.

PMID- 22616201
TI  - Diagnosis by protein analysis of dysferlinopathy in two patients mistaken as
      polymyositis.
AB  - We investigated the clinical and molecular pattern of two young men affected by
      dysferlinopathy, that was first diagnosed as polymyositis. We show that their
      symptoms and clinical course although progressive were peculiar, as well as their
      biopsy suggesting a subsequent analysis of dysferlin protein by western blotting.
      Molecular analysis of dysferlin gene revealed pathogenetic mutations in both
      cases. In such cases a screening with Western blot followed by DNA analysis of
      dysferlin gene is therefore recommended. We present a diagnostic algorythm for
      patients with suspected myositis but presenting signs of disease progression and
      poor response to steroids.

PMID- 22616202
TI  - Sensory ataxic neuropathy with dysarthria/dysphagia and ophthalmoplegia (SANDO).
      Two case reports.
AB  - Case histories of two unrelated patients suffering from sensory ataxic
      neuropathy, dysarthria/dysphagia and external ophthalmoplegia (SANDO) are
      reported. Both patients showed compound heterozygosity for POLG1 gene mutations,
      and presented with symptom of the clinical characteristics of SANDO. A patient
      with a p.A467T and p.W748S, well-known mutations showed a progressive course with
      early onset and multisystem involvement, including symptoms characteristics for
      mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). The second patient
      showed a less well-known p.T251I and p.G848S mutations with late onset and
      dysphagia/dysarthria dominated, moderate symptoms. This later is the second
      published case history, when these POLG1 gene mutations are the possible
      background of late onset SANDO, dominantly presenting with bulbar symptoms.

PMID- 22616203
TI  - Parting questions.

PMID- 22616204
TI  - Power-up: a collaborative after-school program to prevent obesity in African
      American children.
AB  - BACKGROUND: Schools represent a key potential venue for addressing childhood
      obesity. OBJECTIVE: To assess the feasibility of Power-Up, an after-school
      program to decrease obesity risk among African American children, using community
      based participatory research (CBPR) principles. METHODS: Teachers led 14 weekly
      nutrition and physical activity sessions during afterschool care at the Woodlawn
      Community School on Chicago's South Side. Forty African American children ages 5
      to 12 participated; their 28 parents discussed similar topics weekly at pickup
      time, and families practiced relevant skills at home. Pre- and post-intervention
      anthropometrics, blood pressure, dietary measures, and health knowledge and
      beliefs for children and parents were compared in univariate analysis. RESULTS:
      At baseline, 26% of children were overweight; 28% were obese. Post-intervention,
      mean body mass index (BMI) z scores decreased from 1.05 to 0.81 (p<.0001).
      Changes were more pronounced for overweight (-0.206 z-score units) than for obese
      children (-0.062 z-score units; p=.01). Girls decreased their combined prevalence
      of overweight/obesity from 52% to 46%; prevalence across these categories did not
      change for boys. The prevalence of healthful attitudes rose, including plans to
      "eat more foods that are good for you" (77% to 90%; p=.027) and "planning to try
      some new sports" (80% to 88%; p=.007). CONCLUSION: Children in the Power-Up
      program reduced mean BMI z scores significantly. The after-school venue proved
      feasible. The use of CBPR principles helped to integrate Power-Up into school
      activities and contributed to likelihood of sustainability. Engaging parents
      effectively in the afterschool time frame proved challenging; additional
      strategies to engage parents are under development. Plans are underway to
      evaluate this intervention through a randomized study.

PMID- 22616206
TI  - Key informants and community members in community-based participatory research:
      one is not like the other.
AB  - BACKGROUND: As community-based participatory research (CBPR) gains national
      prominence, it is increasingly important to examine critically the meaning of
      community participation and the roles of research participants. Many CBPR
      projects rely heavily on key informants, but because of their social position,
      economic status, or professional role, they may not represent the views of
      community members. OBJECTIVES: This paper compares key informant and community
      member perspectives about neighborhood health to explore the types of knowledge
      produced by each group. METHODS: The data used for this study are part of a
      larger CBPR project, Taking Neighborhood Health to Heart (TNH2H). We conducted
      five focus groups with community members and 16 interviews with key informants.
      RESULTS: Reported knowledge and beliefs about the community generally came from
      three perspectives: Primary key informant (key informant reports about
      neighborhoods and community members), secondary key informant (key informant
      assessments of community member beliefs and motivations for their behaviors), and
      community members. A number of differences emerged between key informants and
      community members in the types of knowledge they shared, revealing important
      assumptions held by key informants about community members. CONCLUSIONS: As more
      funders call for health researchers to engage community members to improve the
      reach, impact, and translation of their research to improve population health,
      they must clarify what is meant by community engagement and recognize the roles
      that people's relative status and positions in society play in their knowledge
      about a given place.

PMID- 22616205
TI  - Community-based participatory approach to reduce breast cancer disparities in
      south Dallas.
AB  - BACKGROUND: South Dallas experiences significant disparities in breast cancer
      mortality, with a high proportion of stage III and IV diagnoses. To address these
      rates, the Dallas Cancer Disparities Community Research Coalition created an
      educational intervention to promote breast health and early detection efforts.
      OBJECTIVES: The goals of the intervention were to increase (a) knowledge
      regarding the chief contributing factors for breast cancer, (b) awareness of the
      importance of screening for early detection, and (c) the proportion of women who
      have engaged in appropriate breast cancer screening practices. METHODS:
      Eligibility criteria for this nonrandomized, controlled trial included women age
      40 and older, English-speaking, and having no personal history of cancer. Control
      participants received written breast health educational materials. Intervention
      participants attended 8 weekly sessions that included interactive educational
      materials, cooking demonstrations, and discussions emphasizing primary and
      secondary breast cancer prevention. All study participants completed a 1-hour
      survey at baseline and 4 months later. RESULTS: There were 59 women were enrolled
      in the intervention and 60 in the control group. At follow-up, after controlling
      for baseline mammography status, women in the intervention group were 10.4 times
      more likely (95% confidence interval [CI], 2.9-36.4) to have received a screening
      mammogram in the last year compared with the control group. Intervention
      participants demonstrated statistically significantly higher rates of breast self
      examination (odds ratio [OR], 3.0; 95% CI, 1.0-8.6) and breast cancer knowledge
      (p=.003). CONCLUSION: Lessons learned from this community-based participatory
      research (CBPR) study can be used to create sustainable cancer disparity
      reduction models that can be replicated in similar communities.

PMID- 22616207
TI  - Community ACTION boards: an innovative model for effective community-academic
      research partnerships.
AB  - BACKGROUND: Community-based participatory research (CBPR) requires equitable
      partnerships between community stakeholders and academics. Traditionally,
      researchers relied on community advisory boards, but these boards often play a
      reactive role limited to a project-by-project basis. The East and Central Harlem
      Health Outcomes (ECHHO) Community Action Board (CAB), however, is an effective,
      proactive group. OBJECTIVES: The ECHHO board sought to identify key strategies
      and tools used to build and sustain the model, and to disseminate lessons learned
      to other community-academic partnerships. METHODS: Current and former board
      members were interviewed and a wide range of related documents was reviewed.
      LESSONS LEARNED: The board became effective when it prioritized action and
      relationship-building, across seven key domains: Shared priorities, diversity,
      participation, transparency, mutual respect and recognition, and personal
      connections. The model is depicted graphically. CONCLUSION: Community advisory
      boards may benefit from reduced emphasis on protocols and procedures, and
      increased attention to building relationships between academics and community
      members.

PMID- 22616208
TI  - Lessons learned in using community-based participatory research to build a
      national diabetes collaborative in Canada.
AB  - BACKGROUND: Using community-based participatory research (CBPR) principles, the
      Canadian First Nations Diabetes Clinical Management Epidemiologic (CIRCLE) study
      documents the current clinical management of type 2 diabetes (T2DM) and
      complications in 19 partnering First Nations (FN) communities. OBJECTIVES: To
      outline the lessons learned in developing and fostering community health
      partnerships, and demonstrate the feasibility of using CBPR in multisite research
      at a national level. METHODS: Investigators developed investigator-FN community
      partnerships from seven Canadian provinces, and research assistants were hired
      from each community to facilitate data collection. Research assistants randomly
      selected patients from each community's diabetes registry, and audited the charts
      of consenting patients from 2006 to 2009 for diabetes indicators in accordance
      with national diabetes guidelines. LESSONS LEARNED: Lessons learned in using CBPR
      on a national scale are outlined by highlighting challenges and facilitating
      factors associated with (1) building collaborative relationships, (2) culture and
      ethics, (3) collaboration and partnership, and (4) innovative avenues of data
      management and dissemination. Lessons learned include the need for a flexible
      research agenda, clear and mutually agreed upon roles, partnership from all
      community levels including Elders, regional coordinators managing several sites,
      and wide-scale dissemination methods. CONCLUSION: The CIRCLE national CBPR
      multisite collaborative is unprecedented in Canada, and provides a feasible model
      for other studies. Using CBPR on a national scale exacerbates challenges commonly
      faced with single-site or multisite research, but the benefits provided in
      developing partnerships based on mutual trust and goals makes it of great
      importance.

PMID- 22616209
TI  - A participatory approach to understanding and measuring patient satisfaction in a
      primary care teaching setting.
AB  - BACKGROUND: Patient satisfaction is a complex, multidimensional concept that is
      difficult to measure. However, there is agreement that understanding the
      expectations of a patient community or "what is important to them" is an
      essential consideration. We chose a participatory approach to address patient
      satisfaction in the context of a primary care teaching clinic. OBJECTIVES: The
      objectives of this project were to use a participatory research team of patients
      staff and researchers to (1) adapt an existing patient satisfaction questionnaire
      (PSQ) to the specific cultural and organizational elements ofa primary care
      teaching clinic, (2) administer the revised questionnaire and use the findings as
      a tool for organizational improvement, with the ultimate goal of increasing
      patient satisfaction, and (3) ensure that all decision making involved patients
      and staff to empower them in the process of organizational change. METHODS: We
      used an iterative, mixed methods approach to conduct this project. An
      interdisciplinary committee composed of members of the patient community,
      clinical and administrative staff, and researchers worked together as the primary
      decision making body. RESULTS: We modified a preexisting questionnaire to address
      the unique care delivery model of the clinic, issues of cultural sensitivity, and
      the need for simplified language and response format. Patient dissatisfaction was
      found to center on continuity and access to care. CONCLUSIONS: The participatory
      approach was critical to our success in understanding and measuring patient
      satisfaction from the patients' perspective. The involvement of the
      interdisciplinary committee and the high level of joint decision making in this
      project represents a unique contribution to assessing primary care patient
      satisfaction.

PMID- 22616210
TI  - Involving faith-based organizations in adolescent HIV prevention.
AB  - BACKGROUND: The rates of sexually transmitted infections (STIs; including
      HIV/AIDS) among African Americans in Flint, Michigan, are among the highest in
      the state. In Genesee County, where Flint is located, the incidence of HIV/AIDS
      cases increased at an average rate of 24% each year from 2003 to 2007 for
      adolescents between the ages of 13 and 19. OBJECTIVES: YOUR Blessed Health (YBH)
      is a multilevel, faith-based HIV prevention program designed to increase HIV
      awareness and knowledge and reduce HIV risk behaviors among African American
      congregations. This article describes one of the five components of the
      intervention--training of faith leaders to implement a sexual health curriculum
      for adolescents in their congregations. METHODS: Staff from YOUR Center, a
      community-based HIV service organization, and researchers from the University of
      Michigan, School of Public Health, partnered with faith-based organizations
      (FBOs) to address HIV/AIDS in Flint, Michigan. RESULTS: Participating FBOs
      selected faith leaders to be trained by YOUR Center staff to implement the YBH
      program in their congregations. Using the HIV Outreach, Prevention and Education
      (HOPE) curriculum, faith leaders from 20 FBOs provided HIV education to 212
      adolescents in Flint, Michigan. CONCLUSION: Study findings demonstrate that faith
      leaders who participate in specific and ongoing HIV prevention education training
      can be useful sexual health resources for youth in faith-based settings.
      Implications for research and practice highlight the advantages of continued
      partnerships between FBOs and public health professionals in future HIV
      prevention efforts for adolescents.

PMID- 22616211
TI  - Evaluation of a community-based, service-oriented social medicine residency
      curriculum.
AB  - BACKGROUND: Educators can create opportunities for physicians-in-training to
      learn about the health care needs of the underserved and expose learners to
      models of care and opportunities for service. OBJECTIVES: We evaluated a
      community-based, service-oriented Social Medicine curriculum for Internal
      Medicine interns and residents initiated in 2007. METHODS: Qualitative data were
      collected through focus groups. CONCLUSIONS: Potent community-based experiential
      learning with adequate time and encouragement to hear clients' stories allowed
      residents to gain an understanding of some of the complex factors that contribute
      to ill health in this population and seemed to influence residents' confidence in
      their skills in working with an undeserved population, particularly a population
      struggling with addiction. However, the curriculum did not provide adequate time
      for facilitated, personal reflection. These data will assist community health
      partnerships in developing their own curricula to address health needs of the
      underserved.

PMID- 22616212
TI  - Using the critical incident technique in community-based participatory research:
      a case study.
AB  - BACKGROUND: Successful community-based participatory research involves the
      community partner in every step of the research process. The primary study for
      this paper took place in rural, Northern California. Collaborative partners
      included an academic researcher and two community based resource centers that
      provide supportive services to people diagnosed with cancer. OBJECTIVES: This
      paper describes our use of the Critical Incident Technique (CIT) to conduct
      Community-based Participatory Research. We ask: Did the CIT facilitate or impede
      the active engagement of the community in all steps of the study process?
      METHODS: We identified factors about the Critical Incident Technique that were
      either barriers or facilitators to involving the community partner in every step
      of the research process. CONCLUSIONS: Facilitators included the CIT's ability to
      accommodate involvement from a large spectrum of the community, its flexible
      design, and its personal approach. Barriers to community engagement included
      training required to conduct interviews, depth of interview probes, and time
      required. Overall, our academic-community partners felt that our use of the CIT
      facilitated community involvement in our Community-Based Participatory Research
      Project, where we used it to formally document the forces promoting and
      inhibiting successful achievement of community aims.

PMID- 22616213
TI  - Objectively assessing a dental practice.

PMID- 22616214
TI  - Postextraction maintenance of the alveolar ridge: rationale and review.
AB  - Alveolar ridge resorption has long been considered an unavoidable consequence of
      tooth extraction and can be a significant problem in implant and restorative
      dentistry. Postextraction maintenance of the alveolar ridge minimizes residual
      ridge resorption and allows placement of an implant that satisfies both esthetic
      and functional criteria. Guided bone-regeneration techniques and the use of bone
      replacement materials have been shown to enhance socket healing and potentially
      modify the resorption process. The prime indication for socket preservation is
      the prevention of alveolar-bone and soft-tissue collapse, which would cause
      unacceptable prosthesis esthetics. This review describes the rationale behind
      socket preservation, and the various techniques and materials used for extraction
      site grafting.

PMID- 22616215
TI  - "Rules of 10"--guidelines for successful planning and treatment of mandibular
      edentulism using dental implants.
AB  - The three "Rules of 10" for treatment planning dental implant therapy in the
      edentulous mandible are designed to improve the success of both the endosseous
      implants and the prosthesis. These "rules" acknowledge and provide a method to
      control the mechanical environment, addressing factors affecting implant and
      prosthesis longevity, including magnitude of forces, resistance of the prosthesis
      against these forces, and the biology of bone and its ability to respond to
      loading environments. The rules specify that for any IRO or ISFP, there must be a
      minimum of 10 mm of alveolar dimension (inferior/superior) and a minimum of 10 mm
      of interocclusal (restorative) dimension measured from the soft-tissue ridge
      crest to the occlusal plane. Additionally, for an ISFP, the anterior/posterior
      distribution of implants must be greater than 10 mm. This article provides
      support in the literature for these rules and illustrates their application in
      the treatment of mandibular edentulism.

PMID- 22616216
TI  - A maxillary fixed bridge supported by dental implants: treatment sequence and
      soft-tissue considerations.
AB  - Reconstruction of a patient's maxillary arch with dental implants is a multi-step
      process that includes esthetics, phonetics, lip support, bone support, occlusion,
      medical and dental history, and patient values. This clinical report details the
      step-by-step process--with a rationale for each step--for one patient who elected
      to reconstruct a maxillary arch with an implant-supported fixed prosthesis.
      Diagnosis, treatment planning, and appointment sequence are described, as is the
      importance of establishing soft-tissue outcomes that enable the patient to
      properly clean the area.

PMID- 22616217
TI  - Use of additive dentistry decreases risk by minimizing reduction.
AB  - This case required enhancement of esthetics and reduction of long-term risk of
      pathologic tooth wear and decay, as well as minimizing erosion caused by innate
      and environmental influences. The author weighed patient expectations, diet,
      treatment of teeth, and age to create a treatment plan that would conserve tooth
      structure while accomplishing the goals of the case. The patient's dentition was
      restored utilizing intact enamel, adhesive dentistry, and etchable ceramic
      materials that require less than 1 mm of occlusal reduction without a significant
      loss of strength. In this case, opening the vertical dimension of occlusion-
      which was done to increase the height of both the maxillary and mandibular
      arches, in keeping with the patient's esthetic desires--eliminated the need to
      remove excessive amounts of healthy tooth structure and facilitated treatment of
      the occlusal dysfunction.

PMID- 22616218
TI  - Down syndrome-associated periodontitis: a critical review of the literature.
AB  - Down syndrome, or trisomy 21 (T21), was first described by John Langdon Down in
      1866. Down identified the phenotypic expression of patients with circulation and
      coordination problems as having Down syndrome. More than a century later, Jerome
      Lejeune hypothesized that nondysjunction during meiosis could lead to trisomy of
      the 21st chromosome. The incidence of T21 is one in 800 to 1,000 live births in
      the United States. Generally, these patients now live to age 50 and some to age
      60. As life expectancy increases, medical and social costs garner greater
      attention. Also, societal changes have allowed for better quality of life. Dental
      practitioners are challenged by the high incidence of early onset aggressive
      periodontal disease in T21; these patients have higher levels of periodontal
      pathogens and periodontitis-associated interproximal bone loss. The complex
      anatomy, physiology, immunology, and microbiology underscore the need for further
      investigation in specific areas related to dental treatment of these patients.
      This article is a critical review of the periodontal research concerning T21.
      Creating awareness enables dental professionals who have the power and knowledge
      to appropriately address the needs of those affected by T21.

PMID- 22616219
TI  - Analysis of bone formation after sinus augmentation using beta-tricalcium
      phosphate.
AB  - Implant placement in the edentulous maxilla often represents a clinical challenge
      due to insufficient bone height after crestal bone resorption and maxillary sinus
      pneumatization. Several graft materials have been evaluated for augmenting the
      maxillary sinus to compensate for the lost vertical dimension. Allografts are
      readily available without the risk of disease transmission and the need for a
      second site surgery. The aim of this case series was to systematically evaluate
      the development and maturation of augmented bone in the maxillary sinus using
      beta-tricalcium phosphate. In 21 to 40 weeks post-sinus elevation, bone biopsies
      were taken and implants placed simultaneously. All specimens were demineralized
      and subjected to staining procedures (ie, Hematoxylin and Eosin [H&E], Goldner's
      staining, and tartrate-resistant acid phosphatase [TRAP]). Total bone increased
      over time, whereas the amount of graft material diminished. A lack of
      inflammatory reaction was noticed with the use of this graft material. In
      addition, TRAP staining revealed the presence of osteoclasts surrounding the
      remaining particles. During a 12-month follow-up, no implant failure or
      complications were observed.

PMID- 22616221
TI  - BIOLASE lasers combine excellent clinical results with ease of use.

PMID- 22616220
TI  - Laser technology: its role in treating and managing periodontal disease.

PMID- 22616223
TI  - [Results of a multicentre clinical trial studying efficacy and safety of Vasocet
      in patients with varicose disease and chronic venous insufficiency].
AB  - Presented in the article are the findings of a multicenter prospective clinical
      trial assessing quality of life of patients with chronic diseases of lower limb
      veins on the background of administration of nonmicronized diosmin (Vasocet).
      Specialized questionnaires (CIVIQ-2) appeared to be the most optimal evaluating
      tools, more precisely catching alterations in patients' quality of life on the
      background of drug therapy.

PMID- 22616222
TI  - Reverse spot bonding: a novel technique for provisionalization with immediate
      dentin sealing.
AB  - Described here is a clinical technique for the creation of predictable, stable,
      and efficient provisionals in combination with the use of immediate dentin
      sealing for partial-coverage posterior ceramic restorations.

PMID- 22616224
TI  - Diabetic angiopathy.
AB  - Peripheral arterial disease is high prevalent in patients with diabetes mellitus.
      The purpose of this review article is to resume ethiogenesis, diagnostic
      methodology and treatment modalities of this condition, also known as diabetic
      angiopathy.

PMID- 22616225
TI  - [Hyperhomocysteinemia and plasma acute-phase proteins in patients with type 2
      diabetes mellitus and severe course of atherosclerosis after vascular
      operations].
AB  - Interdependence between the level of homocysteine and acute-phase proteins was
      assessed in patients presenting with a severe course of atherosclerosis. We
      examined a total of 67 patients aged 62.3 +/- 1.03 years. Of these, 34 patients
      had type 2 diabetes mellitus and 35 were non-diabetic. The diabetic patients were
      found to suffer a severe course of the disease, with 65.6% having a decompensated
      form. We carried out a comparative analysis of the level of homocysteine, C
      reactive protein, and that of fibrinogen. It was noted that diabetic patients
      significantly more often showed high levels of blood-plasma total homocysteine, C
      reactive protein, and that of fibrinogen as compared to nondiabetic patients.
      Hyperhomocysteinemia appeared to correlate with elevated levels of C-reactive
      protein (r = 0.37, p = 0.04) and that of fibrinogen (r = 0.36, p = 0.04) at HbA1c
      > or = 7%. The obtained findings strongly suggest interrelationship of high
      levels of blood-plasma homocysteine and an elevation in acute-phase proteins in a
      decompensated form of diabetes mellitus and the presence of sluggish chronic
      inflammation in all patients, either with or without diabetes mellitus. Inclusion
      of homocysteine measuring and a highly sensitive method for determining C
      reactive protein into the standard of examining patients with atherosclerosis
      improves diagnosis of the pathological condition, while timely correction of the
      impairments revealed promotes a decrease in the risk of the development of
      complications.

PMID- 22616226
TI  - [Intraoperative assessment of blood flow along coronary and internal thoracic
      arteries before and after myocardial revascularization].
AB  - The article deals with intraoperative assessment of the blood flow in the
      coronary arteries and internal thoracic artery before and after myocardial
      revascularization. This is accompanied and followed by ultrasonographic
      characteristics of the coronary blood flow before and after surgical
      intervention, as well as competence of anastomoses and functional state of
      revascularization depending on the degree of the atherosclerotic lesion and the
      diameter of coronary arteries. The average linear and volumetric velocities of
      the blood flow in the coronary arteries were found to depend upon the degree of
      the lesion of coronary arteries, the diameter and capacity of the coronary bed.
      The work was based on studying a total of forty-eight patients presenting with
      coronary artery disease and subjected to myocardial revascularization using the
      internal thoracic artery (ITA). Also determined was efficacy of myocardial
      revascularization in different diameters of the coronary arteries and parameters
      of the ITA blood flow.

PMID- 22616227
TI  - [Immediate and remote outcomes of hybrid and stage-wise treatment for concomitant
      pathology (heart defects and coronary artery disease in patients over 70 years
      old].

PMID- 22616228
TI  - [Radionuclide renal scintigraphy in assessment of nephroprotective effect of
      hypoxic preconditioning for myocardial revascularization under artificial
      circulation].
AB  - OBJECTIVE: Using renal scintigraphy to assess the nephroprotective efficacy of
      hypoxic preconditioning (HP) during myocardial revascularization under the
      conditions of artificial circulation (AC). MATERIALS AND METHODS: We examined a
      total of forty-seven patients with CAD (mean age 52.81 +/- 1.40 years) who
      endured coronary artery bypass grafting (CABG) under AC. All patients were
      randomly divided into 2 groups:patients (n = 16) who during CABG underwent HP
      (study group) and those (n = 31) without renal protection (comparison group). HP
      was performed in the mode of one cycle of 10-minute hypoxemia followed by a 5
      minute period of reoxygenation. Dynamic radionuclide renal scintigraphy with
      99mTc-DTPA was carried out before and 6-7 days after surgical treatment with
      calculating the parameters of the filtrating and excreting renal function.
      RESULTS: The comparison-group patients after CABG were found to have negative
      dynamics of the parameters of the renal filtration activity. Thus there was a
      significant decrease in the mean values of total and individually for each kidney
      glomerular filtration rate (GFR) combined with deceleration of the blood
      clearance. Besides patients of this group showed a significant increase in the
      mean value of the half-period of excretion of the indicator from the
      pelvicalyceal system of the left kidney and the parenchyma of the both kidneys.
      The study group patients showed no alterations in the values of the filtration
      activity of the kidneys as compared with the baseline measures, with the
      exception of the GFR of the right kidney. Thus a decrease in the filtration
      function of either one kidney or both kidneys under the influence of non
      pulsating blood flow was observed only in three (19%) patients and was not
      pronounced. Alterations in the indices reflecting the excretory renal function in
      the study group were also insignificant. CONCLUSION: Radionuclide renal
      scintigraphy makes it possible to objectively and with a high level of the
      informative value to determine the degree and pattern of the effect of open-heart
      surgery on renal functional activity. HPC exerts a nephroprotective effect action
      on the renal functional activity in patients with endured open-heart surgery in
      the conditions of assisted circulation.

PMID- 22616229
TI  - [Endovascular treatment of a female patient with resistant arterial hypertension
      secondary to a renal artery aneurysm].
AB  - Described herein is a successful therapeutic outcome in a female patient
      presenting with resistant arterial hypertension secondary to a gigantic
      intraorganic aneurysm of the right renal artery. Treatment consisted of
      intravascular prosthetic repair of the parenchymatous portion of the renal
      artery, eventually making itpossible to entirely bypass the aneurysmatic sac and
      to restore the lumen of the renal artery, followed by normalization of arterial
      pressure.

PMID- 22616230
TI  - [Results of proximal vertebral arteries endovascular interventions].
AB  - OBJECTIVE: To evaluate immediate and long-term clinical and ultrasound efficacy
      of proximal vertebral arteries stenting. We studied 74 subjects (age 61+/-10
      years) who underwent transluminal balloon angioplasty with stenting of vertebral
      arteries (77 vessels). Technical success (i.e., residual stenosis < 20%) was
      achieved in 95% patients. No events (acute stroke, myocardial infarction, or
      death) were recorded during the procedure or in early postoperative period.
      Clinical improvement was seen in 81% patients presented with symptoms of
      vetebrobasilar insufficiency at the baseline (n = 52). Sixty six patients (89%)
      were followed up in the late postoperative period (6 to 54 months after the
      intervention). No events of acute stroke were recorded in the vertebrobasilar
      circulation. Relapse of vertebrobasilar symptoms after temporary improvement was
      seen in 13% patients. Stent restenosis/occlusion was diagnosed in 36% patients
      although no relationship was revealed between the alteration of stent patency and
      relapse of clinical symptoms. Restenosis correlated with initial stenosis of > or
      = 70% (p < 0.05) and type of stent material. Use of cobalt chromium stents was
      associated with 2-fold decrease of restenosis rate vs non cobalt chromium stents
      (24% vs 50%, respectively, p < 0.05). Therefore, stenting of proximal vertebral
      arteries yields good technical and clinical results. High restenosis rate is a
      major problem of endovascular treatment of atherosclerosis and needs further
      evaluation.

PMID- 22616231
TI  - [Variants of anatomical structure of lower-limb veins as a possible cause of the
      development of primary varicosity].
AB  - In order to reveal anatomical prerequisites for the development of primary
      varicose veins we investigated the structure of the venous system on a total of
      53 adult human cadaveric lower extremities. Congenital morphological grounds
      providing the phlebohaemodynemics of the lower limbs are ambiguous in different
      individual forms. We revealed a total of 18 variants of the structure of deep
      veins, reflecting various stages of the embryonic development. In 34.1% of cases
      we saw the forms characteristic of incomplete reduction and unfinished
      transformation, with 30.2% of cases showing the utmost degree of reduction and
      transformation. An inadequate outflow along the deep veins conditioned by their
      anatomical structure is a prerequisite for the development of valvular
      insufficiency and venous reflux to the superficial veins followed by varicose
      transformation thereof

PMID- 22616232
TI  - [Microfoam truncal scleroobliteration in varicose disease].
AB  - Analysed herein are present-day views on using the technique of
      scleroobliteration of major veins (particularly, microfoam scleroobliteration) in
      treatment for varicose disease. Based on the analysis of literature data,
      attempts are made to systematize the indications for such interventions,
      underlying advantages and disadvantages of the technique, and analysing possible
      complications. A conclusion is drawn that the remote results of microfoam
      scleroobliteration are inferior to those of the currently popular thermal
      obliterating techniques. However, this method oftreatment may under certain
      conditions be used to remove the truncal reflux.

PMID- 22616233
TI  - [Advantages of endovenous laser coagulation in surgical management of varicose
      disease].
AB  - Presented in the article are the results of endovenous laser coagulation of the
      greater saphenous vein in a total of ony hundred seventeen patients suffering
      from varicose disease. Favourable outcomes consisted in achieving complete
      removal of the vertical reflux, accompanied and followed by rapid rehabilitation,
      an utterly low complication rate, and an excellent cosmetic effect obtained.

PMID- 22616234
TI  - [Mixed-aetiology extensive ulcers of the crus: postthrombotic disease and
      gangrenous pyoderma].
AB  - Gangrenous pyoderma (GP) is a rare infectious disease typically manifesting
      itself by utterly painful crural ulcers. Currently, the disease is considered to
      be most likely of an autoimmune origin. The author presents herein a case report
      describing key diagnostic and treatment decisions regarding a 30-year-old woman
      suffering from extensive crural ulcers. Of special interest was the finding that
      this patient's ultrasonographic duplex scanning showed the signs corresponding to
      postthrombotic disease. However, conventional treatment of venous trophic ulcers
      turned out inefficient. The woman was diagnosed as having GP. Topical therapy
      with corticosteroid drugs (combined with autodermoplasty and compression therapy)
      made it possible to achieve complete epithelisation of ulcers. Thus, should
      conventional treatment of venous trophic ulcers result in the patient's failure
      to respond properly, it is necessary to take into consideration the probability
      of gangrenous pyoderma.

PMID- 22616235
TI  - [Use of autovenous tissue for treatment of patients with venous-aetiology lower
      limb trophic ulcers].
AB  - The authors analyse herein the results of using removed dilated autologous veins
      simultaneously with operations aimed at correcting venous blood circulation in a
      total of fifty patients presenting with lower-limb trophic ulcers caused by
      varicose and postthrombotic diseases. The comparison group was composed of forty
      four patients subjected to autodermoplasty. In the postoperative period all the
      patients used mechanical stimulation of angiogenesis for bettering and speeding
      up the process of healing and regeneration of trophic ulcers. The use of
      autovenous plastic material appeared to significantly increase the efficacy of
      treatment of patients. The time of epithelisation averagely amounted to 10 days
      for varicose and 14 days for postthrombotic ulcers. In the control group healing
      of varicose trophic ulcers occurred in 91% and in postthrombotic ulcers in 85% of
      patients. The terms of healing averaged 22 and 29 days, respectively. Autovenous
      plasty of trophic ulcers in comprehensive treatment with correcting operations is
      a method turning out to be superior in its efficacy and healing terms to the
      currently existing wound covers.

PMID- 22616236
TI  - [Immediate outcomes of reconstructive operations for pathological deformity of
      the internal carotid artery].
AB  - OBJECTIVE: To investigate the immediate outcomes of surgical treatment of
      patients presenting with pathological deformity of the internal carotid artery.
      METHODS: The study was based on retrospective analysis of the outcomes of
      surgical management of 142 patients with isolated pathological deformity of the
      internal carotid artery who underwent a total of 166 reconstructive procedures.
      RESULTS: Resection with redressing of the internal carotid artery and
      reimplantation into the old bed was a method of choice of repairing the deformed
      artery (74%). More often it was possible to have performed it in kinking, C- and
      S-shape tortuosity of the internal carotid artery, whereas prosthetic repair was
      more often in coiling (P < 0.05). A positive clinical effect of the operation was
      achieved in 97% of the patients. Neurological efficacy of the performed
      interventions depended upon the baseline degree of cerebrovascular insufficiency
      and the duration of clamping of carotid arteries (P < 0.05). The incidence of the
      development of thrombosis of the reconstructed internal carotid artery (1.2%) did
      not depend on either the form of pathological deformity or the method of
      reconstruction thereof. Cerebral circulation impairments in two (1.2%) cases were
      transitory and in three (1.8%) resulted in ischaemic stroke, one of which having
      become the cause of the patient's death. The index "stroke + lethality from
      stroke" amounted to 2.4%. Neurological complications had been caused by
      rheological impairments, instability of haemodynamics and inadequate redressing
      of the internal carotid artery. CONCLUSION: Analysing the immediate outcomes
      confirmed that surgical treatment of pathological deformity of the internal
      carotid artery is an effective method aimed at preventing cerebral circulation
      impairments and removal of cerebrovascular insufficiency in patients with the
      disease concerned.

PMID- 22616237
TI  - [Hybrid reconstructive interventions in distal aortic dissection].
AB  - The authors report herein the findings of a prospective study including a total
      of 26 patients presenting with distal aortic dissection and treated by prosthetic
      repair of the descending portion of the thoracic aorta. The patients were
      subdivided into two groups, with Group One comprising 15 patients having the
      blood flow directed into the true channel and Group Two composed of eleven
      patients subjected to directing blood flow into the both channels. Twelve (80%)
      Group One patients were found to have thrombosis of the false channel and an
      increase in the true channel's diameter. Five (45%) Group Two patients in the
      remote period developed dilatation of the abdominal aorta requiring distal
      prosthetic repair in three of them. A further two patients intraoperatively
      received uncoated stentgrafts (Djumbodies Dissection System, Saint Come
      Chirurgie, France) inserted into the distal portion of the thoracoabdominal aorta
      in order to provide adequate perfusion of the visceral branches. It was shown
      that local prosthetic repair of the descending thoracic aorta is appropriate only
      in case of the blood flow directed into the true lumen and expansion of the
      compressed true channel of the aorta distal to the reconstruction site by means
      of stenting resulted in better haemodynamic outcomes.

PMID- 22616238
TI  - [Systemic multimodality postoperative analgesia in vascular surgery].
AB  - The study comprised a total of fifty-three patients after endured operations
      performed on the infrarenal portion of the aorta and large vessels of the lower
      extremities. The work was aimed at evaluating quality of postoperative analgesia
      in various regimens of multimodality analgesia based on non-narcotic analgesics.
      The following combinations of the drugs were used: ketoprofen + tramadol;
      lornoxicam + tramadol; paracetamol + tramadol; paracetamol + lornoxicam +
      tramadol. The use in the postoperative period of the above mentioned regimens of
      multimodality analgesics makes it/nmpfble to achieve a good analgesic effect
      without administration of narcotic analgesics. The inclusion of paracetamol into
      the postoperative multimodality analgesia results in a rapid onset of an
      analgesic effect and decreased requirements in prescribing tramadol. In patients
      running a high risk of an ulcerogenic effect of non-steroidal anti-inflammatory
      drugs, postoperative analgesia should be carried out based on paracetamol and
      tramadol whose combination appears to provide a beneficial analgesic effect.

PMID- 22616239
TI  - [Methods of treatment in patients with lower extremity arterial occlusive disease
      in presence of distal arterial lesion. (Part II)].
AB  - This report is based upon the data published in Russian and foreign reference
      sources and represents the analysis of methods of treatment in patients with
      lower extremity arterial occlusive disease in presence of distal arterial lesion.

PMID- 22616241
TI  - [The world's fist successful closure of the wound of the ascending aorta. Russian
      priority].
AB  - The year of 1896 became the starting point in the development of cardiovascular
      surgery, since it was just then that Ludwig Rhen was the first in the world to
      have performed a successful closure of a right-ventricle wound, thus opening up
      the era of active surgical policy in heart wounds. However, tangible progress in
      surgical management of intrathoracic vessels was made later on. One of the
      important stages of this trend was a successful closure of an ascending-aorta
      wound performed by I.I. Dzhanelidze in 1913. It was not only the world's first
      successful operation performed in a traumatic lesion of the ascending aorta but
      also apf intervention giving rise to further development of surgery in this
      field. The present-day notions concerning surgical policy in traumatic lesions of
      intrathoracic vessels are based on the experience of prominent and outstanding
      surgeons of the 20th century. The material for this publication was I.I.
      Dzhanelidze's article entitled "A case of ascending- aorta wound closure" and
      published in 1916.

PMID- 22616240
TI  - [Outcomes of surgical management of elderly and aged patients with complicated
      forms of coronary artery disease].
AB  - The article is dedicated to comparative analysis of surgical management of
      elderly and aged patients presenting with complicated forms of coronary artery
      disease (CAD). Suggested herein is an algorithm of concerning the choice of
      methods aimed at surgical correction of postinfarction aneurysms of the right
      ventricle of the heart and postinfarction ruptures of the interventricular septum
      in these patients, depending on the morphological structure of the right
      ventricular postinfarction aneurysms and postinfarction ruptures of the
      interventricular septum, followed by determining the incidence rate of using
      "complete" and "incomplete" myocardial revascularization in elderly and aged
      patients with complicated forms of CAD depending on peculiarities of the coronary
      blood flow. Also considered herein is efficacy of preventing rethrombosis
      following correction of right-ventricular postinfarction aneurysms and
      thrombectomy. The article is based on studying a total of forty-two 60-to-78-year
      old patients with CAD. The measures taken made it possible to decrease
      postoperative lethality and postoperative complications rate in the patients
      concerned.

PMID- 22616242
TI  - Hybrid surgical management of a patient with an aneurysm of the arch and
      descending portion of the right-sided aorta combined with type B dissection and
      decompensated tracheal stenosis.
AB  - The right-sided aorta is a rare congenital abnormality of the cardiovascular
      system encountered in 0.05-0.1% of cases during roentgenological examinations and
      in 0.04-0.1% of cases of autopsy series. Given utterly low prevalence of this
      pathology, we considered it wise to present herein our own case report dealing
      with hybrid surgical management of a patient suffering from an aneurysm of both
      the arch and descending portion of the right-sided aorta combined with type B
      dissection thereof and decompensated tracheal stenosis. The first stage of the
      operation consisted in prosthetic repair of the distal third of the arch and the
      descending portion of the aorta with the "Vascutek" stent graft 20 mm with type 1
      haemodynamical correction (i. e., re-establishing the blood flow into the true
      channel in the zone of the distal anastomosis) in the conditions of
      extracorporeal circulation (EC) and bihemispheric antegrade cerebral perfusion
      ACP, followed by replantation of the left subclavian artery ostium into the left
      common carotid artery. An aneurysmal growth rate of more than 1 cm a year was
      considered an absolute indication for the second stage of correction of the
      aortic pathology concerned. The second stage included stenting of the thoracic
      portion of the aorta. The TF262C150X Valiant thoracic stent graft was implanted
      into the area of the distal anastomosis with a conduit, followed by positioning
      the TF 323C150X Valiant thoracic system inserted into the distal end of the first
      stent. The use of hybrid techniques (a combination of open and endovascular
      interventions) predetermined the success of surgical management of the patient
      presenting with dissection of the right-sided aorta.

PMID- 22616243
TI  - [Hybrid surgical management of a saccular aneurysm of the aortic arch].
AB  - The present article aims to describe a clinical case of hybrid surgical
      intervention consisting in complete prosthetic repair of the aortic arch in a
      high-risk male patient diagnosed with a gigantic saccular aneurysm of the aortic
      arch. The patient was subjected to a hybrid operation--an operation of
      endovascular prosthetic repair of the thoracic portion of the aorta with the Gore
      Tag stent graft in a combination with bypass grafting of the left common carotid
      and left subclavian arteries with the Gore bifurcated stent graft, autovenous
      aortocoronary bypass grafting of the CA without artificial circulation. The
      postoperative period was uneventful with the patient's favourable convalescence
      and rehabilitation occurring within the shortest terms possible. According to the
      findings of MSCT-aortography, fulfilment of the arteries of the aortic arch with
      contrast medium was satisfactory. The residual cavity of the aneurysm was
      completely isolated from the blood flow, with no endoleak. The arteries of the
      aortic arch were opacified through the bifurcation prosthesis from the ascending
      portion of the aorta. Hybrid surgical interventions appear to possess all
      positive properties of endovascular (according to the findings of the EVAR1 and
      EVAR2 Trials) and traditional open surgery, thus allowing of both avoiding
      threatening complications and minimizing the terms of rehabilitation. This
      technique might thus be considered a useful tool to be included into the basic
      armamentarium of the vascular surgeon as an option of revascularization.

PMID- 22616244
TI  - [Surgical management of a hypertensive young adult suffering from nonspecific
      aortoarteritis accompanied by renal arterial lesions].
AB  - Presented herein is a successful outcome of stagewise surgical management of a
      young adult suffering from nonspecific aortoarteritis accompanied renal artery
      lesions. The patient was subjected to a stagewise intervention consisting of
      stenting of the renal arteries and an open operation, i.e. bilateral aortorenal
      bypass grafting performed with the synthetic stent B-Braun.

PMID- 22616245
TI  - [Traditional open vascular surgery and roentgenosurgical intervention-
      competition or interaction leading to hybrid surgeries?].
AB  - On the basis of data published in Russian and foreign medical literature the
      article analyses traditional open surgical and roentgenosurgical methods of
      treating vascular diseases and the effectiveness of their joint application.

PMID- 22616246
TI  - Thanks for editorial.

PMID- 22616247
TI  - Space maintenance--or appropriate care?

PMID- 22616248
TI  - What is really the problem?

PMID- 22616249
TI  - Including your dental license number in advertisements.

PMID- 22616250
TI  - Frequently asked questions about unemployment benefits.

PMID- 22616251
TI  - Prescription drug-running.

PMID- 22616252
TI  - Benefit payment errors and what to do about them.

PMID- 22616253
TI  - An associate's ethical dilemma.

PMID- 22616254
TI  - Computerized restorative dentistry.

PMID- 22616255
TI  - CAD/CAM in digital dentistry: the lab perspective.

PMID- 22616256
TI  - Detroit's Herman Kiefer dental clinic: a passion for public health dentistry.

PMID- 22616257
TI  - A move to local pay would make no sense.

PMID- 22616258
TI  - DH wants wider pay gap to reflect local market conditions in England.

PMID- 22616259
TI  - Nursing school under threat after reduction in SHA commissions.

PMID- 22616260
TI  - Employers fail challenge to improve staff fitness in time for the Olympics.

PMID- 22616261
TI  - Union seeks royal intervention over NHS rates for jubilee holiday.

PMID- 22616262
TI  - 'Dysfunctional' regulator accepts criticisms and plans for change.

PMID- 22616263
TI  - 'Speaking the truth'.
AB  - Whistleblowers are protected by law, but in practice many nurses still report
      that fear of reprisals and inaction by line managers are dissuading them from
      speaking out about poor care. A radical change of culture is needed within
      healthcare organisations.

PMID- 22616264
TI  - In the market for change.
AB  - The government is pushing the NHS into a closer relationship with the private
      sector, one that could put nursing jobs at risk and destabilise services. The
      Health and Social Care Act signals a shift to a 'mixed economy' where market
      principles are more important than ever.

PMID- 22616265
TI  - Plugging a gap in support.
AB  - People diagnosed with secondary breast cancer are often on almost continuous
      treatment and require high levels of support. However, there is evidence that the
      treatment and care they receive are inadequate. The NHS and voluntary sector
      services need to do more to reach these patients.

PMID- 22616266
TI  - Dangerous beginnings.
AB  - Group B streptococcus (GBS) is a common bacterium that can cause severe illness
      in newborn babies. The risk of GBS being passed from a mother to her baby is
      highest during labour or delivery and there are calls for all pregnant women in
      the UK to be screened for the infection.

PMID- 22616268
TI  - The benefits of creative therapy for people with dementia.
AB  - AIM: To evaluate the use of creative therapy, including dance, drama, music and
      movement, with people who have dementia attending one NHS organisation that
      provides day treatment and inpatient services. METHOD: A one-day training package
      in the use of creative therapy in dementia care was commissioned from a dance
      movement psychotherapist. Creative therapy sessions, including dance, drama,
      music and movement activities were implemented over an eight-week period, a
      minimum of three times a week. Observational outcomes of creative self
      expression, communication, pleasure and enjoyment, and general engagement were
      recorded. FINDINGS: Implementation of creative therapy resulted in improvements
      in creative self-expression, communication, pleasure and enjoyment, and general
      engagement in people with dementia. CONCLUSION: The evaluation has emphasised the
      positive effects of creative or artistic approaches on dementia care, and
      supports previous research on the use of such approaches in NHS dementia care
      services. Further research on the immediate and longer-term outcomes and benefits
      of creative therapy for people with dementia is recommended to support the
      routine availability of such therapy in dementia care.

PMID- 22616267
TI  - The diversity of human factors: illustrating the relevance for nursing.
AB  - This article looks at a selection of human factors tools and activities that may
      be used in nursing practice to improve the safety of patient care. The Human
      Factors Walk-Around tool and the Foresight training programme are highlighted as
      means to raise awareness of systems factors that may compromise safety. Ideas are
      given on how to improve team skills, to consider risk proactively, and to
      influence the design of the healthcare system in which care is delivered.

PMID- 22616270
TI  - Spiritual care.

PMID- 22616269
TI  - Skin flora: implications for nursing.
AB  - Many patients receiving inpatient care or admitted as day cases undergo invasive
      procedures that place them at potential risk of healthcare-associated infection.
      Human skin is populated with microorganisms most of which are harmless, however
      some have pathogenic potential. This article outlines the protective function of
      intact skin and describes its resident and transient microbial flora. The role
      and limitations of antiseptics in reducing the risk of infection are discussed.

PMID- 22616272
TI  - Forging new community services.

PMID- 22616271
TI  - Educated for practice.

PMID- 22616273
TI  - Keeping it personal.

PMID- 22616274
TI  - Assessment package for language development in Japanese hearing-impaired children
      (ALADJIN) as a test battery for the development of practical communication.
AB  - OBJECTIVES: The measurement of language development in hearing-impaired children
      is an important step in assessing the appropriateness of an intervention. We
      proposed a set of language tests (the Assessment Package for Language Development
      in Japanese Hearing-Impaired Children [ALADJIN]) to evaluate the development of
      practical communication skills. This package consisted of communication skills
      (TQAID), comprehensive (PVT-R and SCTAW) and productive vocabulary (WFT),
      comprehensive and productive syntax (STA), and the STRAW. METHODS: A total of 638
      children with greater than 70-dB hearing impairment were subjected to this set of
      language tests. Additional tests, including the PARS, the RCPM, and parental
      questionnaires, were administered to assess the backgrounds of the children.
      RESULTS: A trimodal distribution was observed among hearing-impaired children by
      the histogram-based analysis of each test. CONCLUSIONS: The ALADJIN is a useful
      Japanese-language evaluation kit for hearing-impaired children.

PMID- 22616275
TI  - Effects of early identification and intervention on language development in
      Japanese children with prelingual severe to profound hearing impairment.
AB  - OBJECTIVES: Early identification and intervention for prelingual bilateral severe
      to profound hearing loss is supposed to reduce the delay in language development.
      Many countries have implemented early detection and hearing intervention and
      conducted regional universal newborn hearing screening (UNHS). However, the
      benefits of UNHS in later childhood have not yet been confirmed, although
      language development at school age has a lifelong impact on children's future.
      Our Research on Sensory and Communicative Disorders project attempted to reveal
      the effects of UNHS and those of early intervention on the development of verbal
      communication in Japanese children. METHODS: In this study, 319 children with
      prelingual bilateral severe to profound hearing loss, 4 to 10 years of age, were
      evaluated with the Test of Question-Answer Interaction Development used as an
      objective variable. Participation in UNHS and early intervention were used as
      explanatory variables. The adjusted odds ratio (AOR) was calculated after
      adjusting several confounding factors with use of logistic regression analysis.
      In addition, caregivers' answers were obtained by a questionnaire, and the
      process of diagnosis with and without UNHS was analyzed retrospectively. RESULTS:
      Early intervention was significantly associated with better language development
      (AOR, 3.23; p < 0.01). Participation in UNHS may contribute to better language
      development to some extent (AOR, 1.32), but not one that was statistically
      significant (p = 0.37). However, UNHS was significantly associated with early
      intervention (AOR, 20.21; p < 0.001). The questionnaire results indicated a lag
      in treatment after UNHS in more than 40% of screened cases. CONCLUSIONS: Early
      intervention strongly influenced language development. It is necessary to ensure
      that early identification leads directly to early intervention.

PMID- 22616276
TI  - Language ability in the intermediate-scoring group of hearing-impaired children.
AB  - OBJECTIVES: Language development is a key issue in hearing-impaired children.
      However, interpersonal differences complicate our understanding of the situation.
      The bimodal or trimodal distribution of language scores in our other reports in
      this publication imply the presence of fundamental differences among these
      groups. The characteristic aspects of each group were profiled according to
      language data. METHODS: We divided 268 children with prelingual severe to
      profound hearing impairment into 3 groups according to their trimodal
      distribution observed on histogram-based analysis of their responses to the Test
      of Question-Answer Interaction Development. Test results in several language
      domains, including productive and comprehensive vocabulary, productive and
      comprehensive syntax, and academic achievement, were profiled and compared among
      these 3 groups. RESULTS: Significant differences were observed in the results of
      the Word Fluency Test, the Picture Vocabulary Test-Revised, and the Syntax Test
      of Aphasia among the 3 groups. No significant difference was observed between
      groups who were lower-scoring and intermediate-scoring on the academic
      achievement tests referred to as Criterion Referenced Test-II and the
      Standardized Comprehension Test for Abstract Words. Only the higher-scoring group
      showed excellent results. The demographic factors were not significantly
      different among the 3 groups. CONCLUSIONS: Relatively poor academic achievement
      despite fair language production was the dominant feature of the intermediate
      scoring group. This profile might correlate with academic failure in school.

PMID- 22616277
TI  - Syntactic development in Japanese hearing-impaired children.
AB  - OBJECTIVES: This study examined syntactic development of auditory comprehension
      of sentences in Japanese-speaking school-age children with and without hearing
      impairment. METHODS: In total, 592 preschool and school-age children (421 normal
      hearing and 171 hearing-impaired) were included in this cross-sectional
      observation study conducted using the Syntactic Processing Test for Aphasia for
      Japanese language users. Linear regression analysis was used to determine the
      estimated age at which each syntactic structure was acquired. RESULTS:
      Acquisition of syntactic structures was observed in hearing-impaired and normal
      hearing children. Basic word order sentences of agent-object-verb and the goal
      benefactive construction were acquired at preschool age (earlier group), whereas
      reverse word order sentences of object-agent-verb, source benefactive
      construction, passive voice, and relative clauses were acquired at school age
      (later group). The results showed that many hearing-impaired children may not
      acquire Japanese grammatical structures until the age of 12 years. CONCLUSIONS:
      Adequate screening for language development for school-age hearing-impaired
      children is required for an effective intervention.

PMID- 22616278
TI  - Language development, interpersonal communication, and academic achievement among
      Japanese children as assessed by the ALADJIN.
AB  - OBJECTIVES: Japanese-speaking children in a standard sample were subjected to a
      test battery (ALADJIN: Assessment Package for Language Development in Japanese
      Hearing-Impaired Children) to evaluate the effect of language development on both
      interpersonal communication skills and academic achievement. METHODS: A total of
      414 preschool and school-age children without hearing impairment were included in
      this study. The following tests make up the ALADJIN: the Test of Question-Answer
      Interaction Development (TQAID), the Japanese Language by Criterion Referenced
      Test-II (CRT-II) for measuring academic achievement, the Picture Vocabulary Test
      Revised (PVT-R), the Standardized Comprehension Test of Abstract Words (SCTAW),
      both parts of the Syntactic Processing Test for Aphasia (STA), and the Word
      Fluency Test (WFT). Means and standard deviations at each academic grade level
      were calculated, and a multiple regression analysis was performed. RESULTS: A
      ceiling effect was observed for the TQAID and the STA in children in grade 3 of
      elementary school, and the scores for the PVT-R, SCTAW, and WFT increased
      incrementally according to grade level. Multiple regression analysis revealed
      that the PVT-R, WFT, and STA (production) have predictive power for the results
      of the TQAID (R = 0.59; R2 = 0.58; p <0.0001), whereas the SCTAW and STA
      (comprehension) have predictive power for the results of the CRT-II. CONCLUSIONS:
      Both vocabulary and syntax are important in communication development among
      children. The results of our multiple regression analysis suggest that different
      language domains may play different roles in the development of interpersonal
      communication skills and in academic achievement. The development of
      interpersonal communication skills is largely based on productive vocabulary and
      syntax abilities, whereas academic achievement is largely based on comprehensive
      vocabulary and syntax abilities. Children who have difficulties in either area
      should be evaluated with detailed language assessment tools such as the ALADJIN
      in an effort to aid in the selection of appropriate intervention.

PMID- 22616279
TI  - Assessment of exposure to airborne ultrafine particles in the urban environment
      of Lisbon, Portugal.
AB  - The aim of this study was the assessment of exposure to ultrafine in the urban
      environment ofLisbon, Portugal, due to automobile traffic, and consisted of the
      determination of deposited alveolar surface area in an avenue leading to the town
      center during late spring. This study revealed differentiated patterns for
      weekdays and weekends, which could be related with the fluxes of automobile
      traffic. During a typical week, ultrafine particles alveolar deposited surface
      area varied between 35.0 and 89.2 microm2/cm3, which is comparable with levels
      reported for other towns such in Germany and the United States. These
      measurements were also complemented by measuring the electrical mobility diameter
      (varying from 18.3 to 128.3 nm) and number of particles that showed higher values
      than those previously reported for Madrid and Brisbane. Also, electron microscopy
      showed that the collected particles were composed of carbonaceous agglomerates,
      typical of particles emitted by the exhaustion of diesel vehicles.

PMID- 22616280
TI  - Comparison of seasonal phenol and p-cresol emissions from ground-level area
      sources in a dairy operation in central Texas.
AB  - Although there are more than 200 odor-causing volatile organic compounds (VOCs),
      phenol and p-cresol are two prominent odor-causing VOCs found downwind from
      concentrated animal feeding operations (CAFOs). The VOC emissions from cattle and
      dairy production are difficult to quantify accurately because of their low
      concentrations, spatial variability, and limitations of available instruments. To
      quantify VOCs, a protocol following US. Environmental Protection Agency (EPA)
      Method TO-14A has been established based on the isolation flux chamber method and
      a portable gas chromatograph (GC) coupled with a purge-and-trap system. The
      general objective of this research was to quantify phenol and p-cresol emission
      rates (ERs) from different ground-level area sources (GLASs) in a free-stall
      dairy during summer and winter seasons using this protocol. Two-week-long
      sampling campaigns were conducted in a dairy operation in central Texas. Twenty
      nine air samples were collected during winter and 37 samples were collected
      during summer from six specifically delineated GLASs (barn, loafing pen, lagoon,
      settling basin, silage pile, and walkway) at the free-stall dairy. Thirteen VOCs
      were identified during the sampling period and the GC was calibrated for phenol
      and p-cresol, the primary odorous VOCs identified. The overall calculated ERs for
      phenol and p-cresol were 2656 +/- 728 and 763 +/- 212 mg hd(-1) day(-1),
      respectively, during winter. Overall phenol and p-cresol ERs were calculated to
      be 1183 +/- 361 and 551 +/- 214 mg hd(-1) day(-1), respectively, during summer.
      In general, overall phenol and p-cresol ERs during winter were about 2.3 and 1.4
      times, respectively, higher than those during summer.

PMID- 22616281
TI  - Rapidly eliminating pathogenic microorganisms in large air space using spraying
      *OH radicals.
AB  - A new method for rapidly eliminating pathogenic microorganisms in large air space
      using spraying *OH radicals is presented in this paper With a physical method of
      strong electric-field discharge, large numbers of *OH radicals were produced by
      the oxygen activated particles of O2+, O(1D), O(3P), etc., and the introducing
      reagent HO2-. The gram-positive bacteria Bacillus subtilis, the gram-negative
      bacteria Serratia marcescens, and Bacillus spores were used for the eliminating
      experiments. Results show that the different microorganisms were rapidly killed
      by *OH radicals with a concentration of 0.8 mg/L and spraying density of 21
      microL/m2 within 4 sec. Cell morphological changes were also observed under
      microscope. The cells of B. subtilis and Bacillus spores in their cellular wall,
      cellular membrane, or cell protoplasm were greatly destroyed when being exposed
      to a killing dosage of *OH radicals.

PMID- 22616282
TI  - Volatile organic compound emissions from municipal solid waste disposal sites: a
      case study of Mumbai, India.
AB  - Improper solid waste management leads to aesthetic and environmental problems.
      Emission ofvolatile organic compounds (VOCs) is one of the problems from
      uncontrolled dumpsite. VOCs are well known to be hazardous to human health and
      many of them are known or potential carcinogens. They also contribute to ozone
      formation at ground level and climate change as well. The qualitative and
      quantitative analysis of VOCs emitting from two municipal waste (MSW) disposal
      sites in Mumbai, India, namely Deonar and Malad, are presented in this paper. Air
      at dumpsites was sampled and analyzed on gas chromatography-mass spectrometry (GC
      MS) in accordance with U.S. Environmental Protection Agency (EPA) TO-17
      compendium method for analysis of toxic compounds. As many as 64 VOCs were
      qualitatively identified, among which 13 are listed under hazardous air
      pollutants (HAPs). Study of environmental distribution of a few major VOCs
      indicates that although air is the principal compartment of residence, they also
      get considerably partitioned in soil and vegetation. The CO2 equivalent of target
      VOCs from the landfills in Malad and Deonar shows that the total yearly emissions
      are 7.89E+03 and 8.08E+02 kg, respectively. The total per hour ozone production
      from major VOCs was found to be 5.34E-01 ppb in Deonar and 9.55E-02 ppb in Malad.
      The total carcinogenic risk for the workers in the dumpsite considering all
      target HAPs are calculated to be 275 persons in 1 million in Deonar and 139
      persons in 1 million in Malad.

PMID- 22616283
TI  - Determination of air quality zones in Turkey.
AB  - In this study, the particulate matter (with an aerodynamic diameter <10 microm;
      PM10) profile of Turkey with data from the air quality monitoring stations
      located throughout the country was used. The number of stations (119) was reduced
      to 55 after a missing data treatment for statistical analyses. First, a
      classification method was developed based on ongoing national and international
      (European Commission directives) legislations to categorize air zones into six
      groups, from a "Very Clear Air Zone" to a "Polluted Air Zone". Then, a Geographic
      Information System (GIS)-based interpolation technique and statistical analyses
      (correlation analysis and factor analysis) were used to generate PM10 pollution
      profiles of the annual heating time and nonheating time periods. Finally, the
      coherent air pollution management zones of Turkey, based on air quality criteria
      and measured data using a GIS-based model supported by statistical analyses, were
      suggested. Based on the analysis, four hot spots were identified: (i) the eastern
      part of the Black Sea region; (ii) the northeastern part of inland Anatolia;
      (iii) the western part of Northeastern Anatolia; and (vi) the eastern part of
      Turkey. The possible reasons for the elevated PM10 levels are discussed using
      topographic, climatologic, land use, and energy utilization parameters. Finally,
      the suggested air zones were compared with the administrative air zones, which
      were newly developed by the Turkish Ministry of Environment and Forestry, to
      evaluate the level of agreement between the two.

PMID- 22616284
TI  - Determination of the emissions from an aircraft auxiliary power unit (APU) during
      the Alternative Aviation Fuel Experiment (AAFEX).
AB  - The emissions from a Garrett-AiResearch (now Honeywell) Model GTCP85-98CK
      auxiliary power unit (APU) were determined as part of the National Aeronautics
      and Space Administration's (NASA's) Alternative Aviation Fuel Experiment (AAFEX)
      using both JP-8 and a coal-derived Fischer Tropsch fuel (FT-2). Measurements were
      conducted by multiple research organizations for sulfur dioxide (SO2, total
      hydrocarbons (THC), carbon monoxide (CO), carbon dioxide (CO2), nitrogen oxides
      (NOx), speciated gas-phase emissions, particulate matter (PM) mass and number,
      black carbon, and speciated PM. In addition, particle size distribution (PSD),
      number-based geometric mean particle diameter (GMD), and smoke number were also
      determined from the data collected. The results of the research showed PM mass
      emission indices (EIs) in the range of 20 to 700 mg/kg fuel and PM number EIs
      ranging from 0.5 x 10(15) to 5 x 10(15) particles/kg fuel depending on engine
      load and fuel type. In addition, significant reductions in both the SO2 and PM
      EIs were observed for the use of the FT fuel. These reductions were on the order
      of approximately 90% for SO2 and particle mass EIs and approximately 60% for the
      particle number EI, with similar decreases observed for black carbon. Also, the
      size of the particles generated by JP-8 combustion are noticeably larger than
      those emitted by the APU burning the FT fuel with the geometric mean diameters
      ranging from 20 to 50 nm depending on engine load and fuel type. Finally, both
      particle-bound sulfate and organics were reduced during FT-2 combustion. The PM
      sulfate was reduced by nearly 100% due to lack of sulfur in the fuel, with the PM
      organics reduced by a factor of approximately 5 as compared with JP-8.

PMID- 22616286
TI  - Comparison of on-road emissions for B-0, B-10, and B-20 in transit buses.
AB  - Biodiesels are often marketed as being cleaner than regular diesel for emissions.
      Emission test results depend on the biodiesel blend, but laboratory tests suggest
      that biodiesels decrease particulate matter, carbon monoxide, hydrocarbons, and
      air toxins when compared to regular diesel. Results for the amount of oxides of
      nitrogen (NOx) have been less conclusive. Tests have also not evaluated the
      commonly available ranges of biodiesel blends in the laboratory. Additionally,
      little information is available from on-road studies, so the effectiveness of
      using biodiesels to reduce actual emissions is unknown. A more complex
      relationship exists between engine operation and the rate of emission production
      than is typically evaluated using engine or chassis dynamometer tests. On-road
      emissions can vary dramatically because emissions are correlated to engine mode.
      Additionally, activity such as idling, acceleration, deceleration, and operation
      against a grade can produce higher emissions than more stable engine operating
      modes. Because these modes are not well captured in a laboratory environment,
      understanding on-road relationships is critical in evaluating the emissions
      reductions that may be possible with biodiesels. More tests and quantifications
      of the effects of different blends on engine and vehicle performance are required
      to promote widespread use of biodiesel. The objective of this research was to
      conduct on-road tests to compare the emission impacts of different blends of
      biodiesel to regular diesel fuel under different operating conditions. The team
      conducted on-road tests that utilized a portable emissions monitoring system that
      was used to instrument transit buses. Regular diesel and different blends of
      biodiesel were evaluated during on-road engine operation by instrumenting three
      in-use transit buses, from the CyRide system of Ames, Iowa, along an existing
      transit route.

PMID- 22616285
TI  - Development of outcome-based, multipollutant mobile source indicators.
AB  - Multipollutant indicators of mobile source impacts are developed from readily
      available CO, NOx, and elemental carbon (EC) data for use in air quality and
      epidemiologic analysis. Two types of outcome-based Integrated Mobile Source
      Indicators (IMSI) are assessed. The first is derived from analysis of emissions
      of EC, CO, and NOx such that pollutant concentrations are mixed and weighted
      based on emission ratios for both gasoline and diesel vehicles. The emission
      based indicators (IMSI(EB)) capture the impact of mobile sources on air quality
      estimated from receptor models and their uncertainty is comparable to measurement
      and source apportionment uncertainties. The IMSI(EB) have larger correlation
      between two different receptor sites impacted by traffic than single pollutants,
      suggesting they are better indicators of the local impact ofmobile sources. A
      sensitivity analysis of fractions of pollutants in a two-pollutant mixture and
      the inclusion in an epidemiologic model is conducted to develop a second set of
      indicators based on health outcomes. The health-based indicators (IMSI(HB)) are
      weighted combinations of CO, NOx, and EC pairs that have the lowest P value in
      their association with cardiovascular disease emergency department visits,
      possibly due to their better spatial representativeness. These outcome-based,
      multipollutant indicators can provide support for the setting of multipollutant
      air quality standards and other air quality management activities.

PMID- 22616287
TI  - Optimizing nutrient supply in a rotatory-switching biofilter for toluene vapor
      treatment.
AB  - The influence of nutrient conditions on the degradation of toluene vapor in a
      rotatory-switching biofilter (RSB) was investigated. The biofilter consists of
      four segments connected in series, each with a packing layer made of polyvinyl
      formal. The influent airstreams including toluene vapors were passed through
      segments 1-3 as up-flow with a toluene concentration of 0.9-1.2 g m(-3) and with
      an empty-bed retention time of 26-52 sec. Nutrient solutions were fed to all
      packed segments once a day by means of immersion. The nutrient solution was used
      repeatedly and replenished by the addition of (NH4)2SO4. The result at 155 days
      showed nitrogen depletion was particularly obvious and the lack of nitrogen
      affected toluene removal. By adding 161 g of nitrogen solution per volumetric
      cubic meter of reactor, toluene removal efficiency was immediately increased to
      greater than 99%. With long-term biofilter operation, 21%-32% of ammonium was
      utilized for nitrification because of the growth of nitrifying bacteria such as
      Nitrosomonas sp. Based on the carbon-nitrogen balance, the daily nitrogen demand
      for toluene removal was estimated 2.1 g day(-1) at a toluene load of 70 g m(-3)
      hr(-1).

PMID- 22616288
TI  - The emission patterns of volatile organic compounds during aerobic biotreatment
      of municipal solid waste using continuous and intermittent aeration.
AB  - Because volatile organic compounds (VOCs) are one of the main concerns during
      municipal solid waste (MSW) treatment, the release patterns and the environmental
      effects of VOCs were investigated during laboratory-scale aerobic biotreatments
      of MSW with continuous and intermittent negative ventilation. When the same
      airflow amounts were used, intermittent ventilation was found to reduce the total
      VOC emissions from continuous ventilation process by 28%. In this study, 23 types
      of volatile organic compounds were analyzed, of which butyraldehyde, ethanol, and
      butanone were emitted in the highest concentrations of 748, 372, and 260 mg/m3,
      respectively. During the aerobic biotreatment process, ketones, aldehydes, and
      alcohols were primarily released during the first 4 days, accounting for 86-98%
      of the total VOC emissions during this period. The emission concentrations of
      malodorous sulfide compounds displayed two peaks on day 4 and day 9, with the
      contribution to the total VOC emissions being enhanced from less than 10% to 76
      83%. The release of terpenes and aromatics lasted for more than 10 days with no
      significant emission peaks and the proportions of those compounds in the total
      VOCs increased gradually, but no more than 50% even at the end of the process.
      Considering the strength of the odors, aldehydes were the predominant
      contributors at the beginning of the experiment, whereas malodorous sulfide
      compounds became the most odorous compound as the biological process continued.
      Most of the VOCs emitted at the concentrations beneath the level causing health
      threat to the workers.

PMID- 22616289
TI  - Effects of improved spatial and temporal modeling of on-road vehicle emissions.
AB  - Numerous emission and air quality modeling studies have suggested the need to
      accurately characterize the spatial and temporal variations in on-road vehicle
      emissions. The purpose of this study was to quantify the impact that using
      detailed traffic activity data has on emission estimates used to model air
      quality impacts. The on-road vehicle emissions are estimated by multiplying the
      vehicle miles traveled (VMT) by the fleet-average emission factors determined by
      road link and hour of day. Changes in the fraction of VMT from heavy-duty diesel
      vehicles (HDDVs) can have a significant impact on estimated fleet-average
      emissions because the emission factors for HDDV nitrogen oxides (NOx) and
      particulate matter (PM) are much higher than those for light-duty gas vehicles
      (LDGVs). Through detailed road link-level on-road vehicle emission modeling, this
      work investigated two scenarios for better characterizing mobile source
      emissions: (1) improved spatial and temporal variation of vehicle type fractions,
      and (2) use of Motor Vehicle Emission Simulator (MOVES2010) instead of MOBILE6
      exhaust emission factors. Emissions were estimated for the Detroit and Atlanta
      metropolitan areas for summer and winter episodes. The VMT mix scenario
      demonstrated the importance of better characterizing HDDV activity by time of
      day, day of week, and road type. More HDDV activity occurs on restricted access
      road types on weekdays and at nonpeak times, compared to light-duty vehicles,
      resulting in 5-15% higher NOx and PM emission rates during the weekdays and 15
      40% lower rates on weekend days. Use of MOVES2010 exhaust emission factors
      resulted in increases of more than 50% in NOx and PM for both HDDVs and LDGVs,
      relative to MOBILE6. Because LDGV PM emissions have been shown to increase with
      lower temperatures, the most dramatic increase from MOBILE6 to MOVES2010 emission
      rates occurred for PM2.5 from LDGVs that increased 500% during colder wintertime
      conditions found in Detroit, the northernmost city modeled.

PMID- 22616290
TI  - Characteristics of penicillin bacterial residue.
AB  - IMPLICATIONS: During the production of penicillin, a mass of waste bacterial
      residue is generated. In the past, the bacterial residues have been used for food
      additives. Unfortunately, doubts of their suitability as a feedstock have been
      raised because of the small amount of antibiotics and the degradation products
      remaining in the bacterial residues. So, penicillin bacterial residue is one of
      the hazardous wastes. Therefore, penicillin bacterial residue should be managed
      in accordance with the hazardous waste. To get a right method, the penicillin
      bacterial residue was characterized.

PMID- 22616291
TI  - Nursing an academic profession!

PMID- 22616292
TI  - Student dilemma.

PMID- 22616293
TI  - Complementary therapies.

PMID- 22616294
TI  - The third space.

PMID- 22616295
TI  - Graduate succeeds against the odds!

PMID- 22616296
TI  - Health care workers and vaccination.

PMID- 22616297
TI  - Employers pushing WorkChoices agenda.

PMID- 22616298
TI  - Our older Australians: worth caring for.

PMID- 22616299
TI  - Recognising difference: the need to develop culturally appropriate care.

PMID- 22616300
TI  - Michelle Orr: Mental health nurse practitioner candidate.

PMID- 22616301
TI  - Nurses and ethical conflict with employer organisations.

PMID- 22616302
TI  - Care of the type 1 latex allergy patient.

PMID- 22616303
TI  - Management of clients with Alzheimer's dementia and co-morbid depression.

PMID- 22616304
TI  - Health life with cranberry.

PMID- 22616305
TI  - Managing terminal dementia.

PMID- 22616306
TI  - Impact of a death on other residents in aged care.

PMID- 22616307
TI  - Exercise to reduce effects of sarcopenia.

PMID- 22616308
TI  - First in aged care education: uni and industry collaborate.

PMID- 22616309
TI  - Residential aged care facilities: part of the educational tea.

PMID- 22616310
TI  - A palliative approach in aged care.

PMID- 22616311
TI  - AsthmaWise: helping older adults manage their asthma.

PMID- 22616312
TI  - Nurses and midwives forced on to the streets.

PMID- 22616313
TI  - Physician survey examining the impact of an educational tool for responsible
      opioid prescribing.
AB  - INTRODUCTION: In response to the need for physician education on proper opioid
      prescribing, the Federation of State Medical Boards (FSMB) and the FSMB
      Foundation, the philanthropic arm of the FSMB, commissioned and distributed
      Responsible Opioid Use: A Physician's Guide to more than 165, 000 licensed
      physicians in the United States. The book, written by pain management specialist
      Scott Fishman, MD, seeks tofurtherphysicians' continuing medical education by
      providing information on how to properly prescribe opioids to treat patients in
      pain. Although the book has been widely distributed, there have been no
      systematic studies of its impact. To address this knowledge gap, the authors
      surveyed licensed physicians in Georgia who received a copy of the book to
      determine whether it added to their knowledge about prescribing opioids, and if
      they planned to make changes in theirpractice based on reading the book. METHODS:
      Six weeks after licensed physicians in Georgia received the book, a survey was
      sent to 12,666 of them via e-mail. RESULTS: A total of508 physicians completed
      the online survey. Of these, 82.1 percent rated the book either "very good" or
      "good" on providing pragmatic steps for improved care forpatients in pain, and
      more than 80 percent agreed that the book is a useful educational tool. Almost
      one-third (32.2percent) claimed that they intend to make changes to theirpractice
      after reading the book. The analysis also showed physicians in a solo practice
      were more likely to make changes (41.8percent) than their counterparts in office
      based group practice (33.3 percent) and hospital-based (25.0 percent) settings.
      Primary care providers (41.6 percent) were also much more likely to make changes
      than physicians working in other specialty areas of medicine (22.8 percent). Well
      over half (57. 7percent) of the respondents indicated the book was better than
      other publications they had read on opioid prescribing and pain management.
      CONCLUSIONS: The results from this state-wide survey of licensed physicians
      demonstrate the value of educating physicians about how to appropriately
      prescribe, document, and treat patients who need opioid medications for pain
      management. The findings should be of value to organizations seeking to better
      educate physicians about appropriate opioid prescribing by providing insight into
      which physician population would be the most receptive to the type of information
      presented in Dr. Fishman's book. When faced with limited resources, an
      organizational strategy that first targets solo and primary care practitioners
      may improve physician educational efforts about prescribing opioids better than a
      strategy targeting medical and surgical specialists or those physicians
      participating in group practice settings.

PMID- 22616314
TI  - Tolerability and efficacy of two synergistic ratios of oral morphine and
      oxycodone combinations versus morphine in patients with chronic noncancer pain.
AB  - OBJECTIVES: Analgesic synergy and improved tolerability have been reported for
      flexible dose morphine and oxycodone combinations. This report describes two
      studies with similar double-blind, randomized, 7-day crossover designs (up to 7
      days per arm) conducted to 1) explore the analgesic and safety benefit offixed
      ratio of morphine (M) and oxycodone (0) combinations (MOX) and 2) define the
      optimal ratio for morphine and oxycodone combination. SETTING: Clinical study
      centers in Australia. PATIENTS: Patients with chronic noncancer pain.
      INTERVENTION: Eligible patients were randomly assigned to receive flexible doses
      of either M or fixed ratio of MOX (M3:02 in study A; M1:02 in study B). The
      starting doses of M or MOX were the morphine equivalent doses (MEDs) converted
      from the analgesics received before entering double-blind treatment. At each
      crossover period, the doses were titrated to achieve analgesia at steady state,
      which was defined as when the same total daily dose (+/-10 percent) had been
      given consecutively for 3 days. MAIN OUTCOME MEASURE: The primary endpoint was
      the study medication dose (MED), which produced adequate pain control at steady
      state. RESULTS: Analgesic synergy in MOX was observed in both studies. On an MED
      basis, 61.6 percent (study A, M:0 = 3:2) or 46.8 percent (study B, M:0 = 1:2)
      more MED were needed forM monotherapy to achieve steady-state pain control when
      compared with MOX. Patient tolerability profiles were also generally better in
      the MOX groups. CONCLUSION: A 3:2 or 1:2 fixed ratio combination of morphine and
      oxycodone (MOX) produced analgesic synergy and a tolerability profile improvement
      in patients with chronic noncancer pain.

PMID- 22616315
TI  - Continuous hydromorphone for pain and sedation in mechanically ventilated infants
      and children.
AB  - OBJECTIVE: To describe dosing regimens and efficacy of continuous infusion
      hydromorphone in mechanically ventilated children. DESIGN: Retrospective review.
      SETTING: Tertiary care, pediatric hospital. PATIENTS: Ninety-two critically ill
      children (<18 years old). MAIN OUTCOME MEASURE(S): Hydromorphone dosing
      requirements, concomitant pain and sedation therapy, patient-specific pain scores
      (using Face Legs Activity Cry Consolability [FLACC] pain scale), and possible
      adverse drug events related to therapy. RESULTS: Starting dose was 0.024 +/- 0.04
      mg/kg/h. Maximum dose was 0.05 + 0.1 mg/kg/h. Duration of therapy was 182 +/- 169
      hours. Most patients received additional pain and sedation therapy. Most mean
      daily FLACC scores (66 percent) were below 1. Less than 10 percent of scores were
      above 3; only 1 score was above 6. Mean FLACC score, when averaged per patient
      course, was 1.004 +/- 0.71. Extracorporeal membrane oxygenation (ECMO) patients
      had a significantly higher initial and maximum dosing requirement than non-ECMO
      patients (p = 0.001). CONCLUSIONS: Continuous infusion hydromorphone appears to
      be an effective adjunctive analgesic in mechanically ventilated children.

PMID- 22616316
TI  - A comparative study on the effects of intrathecal morphine added to
      levobupivacaine for spinal anesthesia.
AB  - OBJECTIVE: In this prospective, randomized, double-blind, controlled study, we
      investigated the sensory, motor, and analgesic block characteristics oftwo
      diferent doses of morphine compared with saline when added to 0.5 percent
      levobupivacaine. DESIGN: Prospective, randomized, double-blinded, controlled
      study. SETTING: University hospital. PATIENTS, PARTICIPANTS, INTERVENTIONS: One
      hundred and twelve ASA I or II adult patients undergoing cesarean section with
      combined-spinal epidural anesthesia (CSEA) were randomly allocated to receive 0.5
      mL of0.9 percent sodium chloride in group S, 0.1 mg of morphine in group M1, or
      0.2 mg of morphine in group M2 following 15 mg of isobaric spinal levobupivacaine
      0.5 percent (3 mi). MAIN OUTCOME MEASURE(S): We recorded the following: onset and
      duration of sensory and motor block, duration of spinal anesthesia, time to first
      request for analgesia, and side effects. RESULTS: The onset time ofsensory block
      was significantly less in group M2 (3.5 + 3 minutes) than S (4 +/- 3 minutes; p <
      0.003). Parturientsgiven morphine had a significantly greater duration of
      analgesia (554 +/- 350 minutes in group M1 and 879 -725 minutes in group M2) than
      the saline group (80 +/- 70 minutes; p < 0.001). Similarly, the time to first
      request for analgesia was longer in groups M1 (582 +/- 470 minutes) and M2 (917+/
      709 minutes) than in group S (92 +/- 77 minutes; p < 0.001). CONCLUSION: In
      patients undergoing cesarean delivery with CSEA, adding intrathecal morphine (0.1
      and 0.2 mg) to 15 mg of spinal levobupivacaine prolonged the duration of spinal
      analgesia and provided rapid onset of action and longer time to first analgesic
      request without causing any significant side effect compared to saline.

PMID- 22616317
TI  - Safety of EMBEda (morphine sulfate and naltrexone hydrochloride) extended-release
      capsules: review of postmarketing adverse events during the first year.
AB  - BACKGROUND: EMBEDA@ (morphine sulfate and naltrexone hydrochloride) extended
      release capsules, indicated for management of chronic, moderate-to-severe pain,
      contain pellets of morphine sulfate with a core of sequestered naltrexone, an
      opioid antagonist. OBJECTIVE: To review postmarketing adverse event (AE) reports
      received during first year following approval. METHODS: All postmarketing AEs
      reported to the manufacturer were reviewed. RESULTS: During the reporting period,
      approximately 97,000 prescriptions for EMBEDA were dispensed. One hundred eighty
      two case reports containing 429 events were reviewed; 33 (18 percent) were
      reported as serious and 149 (82 percent), as non-serious. Of 429 AEs reported,
      the most common were drug ineffective (7 percent), headache (6 percent), drug
      withdrawal syndrome (6 percent), and nausea (4 percent). Seven cases involved
      oral overdose; of these, two suicide attempts resulted in fatalities. Product
      tampering was confirmed in six cases; suspected in five. No cases of confirmed
      tampering resulted in fatality; none resulted in symptoms typically associated
      with opioid overdose. Three were associated with opioid withdrawal symptoms,
      suggesting that naltrexone released during tampering potentially blocked the
      opioid effects. Twenty-five cases involving reported withdrawal or symptoms of
      withdrawal were reviewed; most were associated with dose interruption, capsule
      manipulation, history of drug abuse, or intolerance to a new opioid regimen.
      CONCLUSIONS: Results suggest that the safety profile of EMBEDA is consistent with
      that of an extended-release morphine formulation. Reports of exposure to tampered
      product yielded either withdrawal reactions or events not typical of opioid
      abuse. The clinical effects of EMBEDA in the context of misuse and abuse require
      further clinical and epidemiological exploration.

PMID- 22616319
TI  - A remifentanil/ketamine sedation in surgical cancer patients having severe
      Parkinson's disease: two case reports.
AB  - Symptoms of Parkinson's disease are related to a progressive loss of substancia
      nigra's dopaminergic neurons in addition to persistent activation of N-methyl-D
      aspartate receptors. In specific situations such as sedation for minor surgery,
      tremor and dyskinesia can be very disabling. We report the beneficial effect of
      the combination of remifentanil (target-controlled infusion mode) and ketamine
      (boluses IV) to control dyskinesia and tremor for two elderly patients with
      Parkinson's disease. The patients were scheduled for elective oncological plastic
      surgery under sedation, for which dyskinesia and tremor needed to be quickly
      abolished to permit surgery. Both procedures were completed with this drug
      combination resulting with no major side effects.

PMID- 22616320
TI  - Who's driving health care's transformation?

PMID- 22616318
TI  - Do transdermal opioids affect the personal socioeconomic costs of healthcare
      access in an australian rural pain population? A comparison with oral opioids.
AB  - OBJECTIVE: To determine whether there are differences in the personal
      socioeconomic costs of healthcare access between transdermal (TD) and oral opioid
      use in a rural population with chronic noncancer pain (CNCP). DESIGN: An
      observational longitudinal study, measuring change in the self-reported personal
      time and expense of healthcare access by route of opioid administration over time
      (monthly for 1 year). Subjects were opioid treated patients with CNCP from North
      West Tasmania, Australia. Subjects completed monthly datasheets by recording all
      personal healthcare access time and expense, together with the route(s) of opioid
      administration. The outcome measures of mean monthly healthcare time (MHT) and
      expense (MHE), by route of opioid administration, were analyzed using generalized
      estimating equations with robust standard errors. RESULTS: The details of 10,564
      healthcare contacts from 198 subjects were obtained during the study. Total mean
      MHT with oral opioids was 3.76 hours (95% confidence interval [CI] = 2.21-5.32)
      and unchanged (p = 0.59) with TD opioids at 3.48 hours (95% CI = 2.23-4.72).
      Total mean MHE with oral opioids was AU$ 92.72 (95% CI = 51.21-134.24) and
      unchanged (p = 0.81) with TD opioids atAU$ 89.12 (95% CI = 54.53-123.71).
      CONCLUSIONS: The personal socioeconomic costs of healthcare access for rural
      patients with CNCP are similar for TD and oral opioid use. The prolonged
      analgesic affect of TD opioids may be advantageous for rural population.

PMID- 22616321
TI  - Caring for vulnerable populations.

PMID- 22616322
TI  - A second opinion. Is it really an emergency?

PMID- 22616323
TI  - Forecast: cloudy. Are you ready to navigate the cloud?

PMID- 22616324
TI  - Wellness proves good (for) business.

PMID- 22616325
TI  - Big demands for data center reliability.

PMID- 22616326
TI  - Burned out or fired up?
AB  - Unprecedented pressures are prompting some hospital CEOs to leave the field.
      Others see a once-in-a-lifetime career opportunity.

PMID- 22616327
TI  - Time to rise to the challenge. Interviewed by Matthew Weinstock.

PMID- 22616328
TI  - Hospitals get aggressive, and infections plunge.
AB  - One hospital targeted surgical-site infections, another MRSA, a third CLAUTI, a
      fourth CLABSI. The results are all remarkable.

PMID- 22616329
TI  - Surgical robots: worth the investment?

PMID- 22616330
TI  - One small hospital one big mission.

PMID- 22616332
TI  - Compassionate care.

PMID- 22616333
TI  - Enhancing value in care delivery.

PMID- 22616334
TI  - Vitamin D deficiency: Indian scenario.

PMID- 22616335
TI  - Vitamin D status and bone mineral density in women of reproductive and
      postmenopausal age groups: a cross-sectional study from south India.
AB  - INTRODUCTION: This study documents 25(OH)D status and bone mineral density (BMD)
      in women of reproductive (WR) and post-menopausal (PMW) age-groups in south
      India. SUBJECTS AND METHODS: Serum calcium (Ca), phosphorus (iP), albumin,
      alkaline phosphatase (ALP), creatinine, 25(OH)D and intact parathormone (N-tact
      PTH) of WR (n = 55) and PMW (n = 136) women were analyzed over a period of one
      year. Bone mineral Density (BMD) (Hologic, USA) was estimated using Caucasian
      data as reference. RESULTS: In both, WR and in PMW 25(OH)D deficiency (< 20
      ng/ml), insufficiency (20-30 ng/ml) and replete states (> 30 ng/ml) were seen in
      76%, 16.5%, 7.5% vs 70%, 23% and 7% respectively. PMW had lower BMD (gm/cm2) than
      WR at forearm ( P = < 0.001), hip trochanter (P = < 0.0001), lumbar spine antero
      posterior (LSAP) (P = < 0.001) and lateral (LS Lateral) (P = < 0.001).
      Osteoporosis was seen at hip (15% and 28%), forearm (nil and 11%), LSAP (6% and
      22%) and LS lateral (0% and 23%) among WR and PMW respectively. BMD did not
      correlate with any of the biochemical indices but correlated with BMD at other
      sites. CONCLUSIONS: Vitamin D deficiency coexists with low BMD in our study
      group. Serum 25(OH)D needs to be documented in women having low BMD. Calcium and
      vitamin D need to be supplemented as part of therapy in PMW.

PMID- 22616336
TI  - Vitamin D status in healthy Indians aged 50 years and above.
AB  - INTRODUCTION: There is widespread prevalence of vitamin D deficiency from new
      born to infancy, childhood and adult male and females (non-pregnant, pregnant and
      lactating). However, there is limited information of the vitamin D status in
      elderly Indians. MATERIAL AND METHODS: The study was carried in 1346 healthy
      subjects more than 50 years of age residing in Delhi, India. These subjects, who
      were divided in two groups: Group-1 (50-< 65 years) and Group-2 (> or = 65
      years), underwent anthropometric, biochemical and hormonal evaluation for vitamin
      D status Bone mineral density was measured by dual X-ray absorptiometry. RESULTS:
      There were 643 males and 703 females, with a mean age of 58.0 +/- 9.5 years
      (range 50-84 years). Vitamin D deficiency [VDD, serum 25(OH)D levels < 20 ng/ml)
      was present in 1228 (91.2%) and Vitamin D insufficiency [VDI, serum 25(OH)D
      levels 20-< 30 ng/ml] in 92 (6.8%). There was no significant difference in
      prevalence of either VDD or VDI between two age groups and sexes. Serum 25(OH)D
      levels were negatively correlated with PTH levels (r -0.027, p <0.00001) and BMI
      (r -0.128, p 0.05). Prevalence of secondary hyperparathyroidism increased from
      14.1% to 43.1% from VDI to severe VDD. PTH levels started rising at vitamin D
      level < 30 ng/ml. However, more than 50% of subjects with severe VDD had PTH
      levels within normal range. High prevalence of osteopenia (50.2%) and
      osteoporosis (31.2%) was observed in this population. CONCLUSION: Hypovitaminosis
      D is universal above the age of 50 years in north India. Absence of a PTH
      response was observed in more than 50% of individuals with VDD, the cause of
      which merits further evaluation. Normal bone mass was observed in only 18.6% of
      study subjects.

PMID- 22616337
TI  - Reinforcement of adherence to prescription recommendations in Asian Indian
      diabetes patients using short message service (SMS)--a pilot study.
AB  - OBJECTIVES: To investigate the acceptability and feasibility of using short
      message services (SMS) via cell phones to ensure adherence to management
      prescriptions by diabetic patients. METHODS: Type 2 diabetic patients with 5 or
      more years of diabetes and having HbA1c between 7.0% to 10% were randomized to
      the control arm (n = 105) to receive standard care and to the intervention arm
      (SMS, n = 110). Messages in English on principles of diabetes management were
      sent once in 3 days, the contents and frequencies varied as per the patients'
      preferences. The study duration was 1 year. All participants were advised to
      report for quarterly clinic visits. A comparative assessment of the clinical,
      biochemical and anthropometric outcomes was made among the groups at the annual
      visit. RESULTS: Annual review was possible in 71% of intervention group and 63%
      of control group. SMS was acceptable to the patients and the median number
      requested was 2 per week. HbA1c and plasma lipids improved significantly in the
      SMS group. CONCLUSIONS: The pilot study showed that frequent communication via
      SMS was acceptable to diabetic patients and it helped to improve the health
      outcomes.

PMID- 22616338
TI  - Cardiovascular disease in live related renal transplantation.
AB  - Cardiovascular disease has become the leading cause of morbidity and mortality in
      renal transplant recipients, although its pathogenesis and treatment are poorly
      understood. Modifiable cardiovascular risk factors and graft dysfunction both
      play an important role in development of post transplant cardiovascular events.
      Prevalence of cardiovascular disease was studied in stable kidney transplant
      patients on cyclosporine based triple immunosuppression in relation to the
      various risk factors and post transplant cardiovascular events. Analysis of 562
      post transplant patients with stable graft function for 6 months, the patients
      were evaluated for cardiovascular events in post transplant period. Pre and post
      transplant risk factors were analyzed using the COX proportional hazard model.
      174 patients had undergone pre transplant coronary angiography, 15 of these
      patients underwent coronary revascularization (angioplasty in 12, CABG in 3). The
      prevalence of CAD was 7.2% in transplant recipients. Of 42 patients with CAD 31
      (73.8%) had cardiovascular event in post transplant period. Age > or = 40 yrs,
      male sex, graft dysfunction, diabetes as primary renal disease, pre transplant
      cardiovascular event, chronic rejection showed significant correlation in
      univariate analysis and there was significant between age > or = 40 years (OR =
      2.16 with 95% CI, 0.977-4.78) S creatinine > or = 1.4 mg % (OR = 2.40 with 95%
      CI, 1.20 - 4.82), diabetes as primary disease (OR with 95% CI 3.67, 3.2-14.82),
      PTDM (OR 3.67, 95% CI 1.45-9.40), pre-transplant cardiovascular disease (OR 4.14,
      95% CI .38-13.15) with post transplant cardiovascular event on multivariate
      analysis. There was poor patient and graft survival among those who suffered post
      transplant cardiovascular event. The incidence of cardiovascular disease
      continues to be high after renal transplantation and modifiable risk factors
      should be identified to prevent occurrence of events in post transplant period.

PMID- 22616339
TI  - The mitral valve: characterisation by real-time three-dimensional transesophageal
      echocardiography. Current status.
AB  - The complex anatomy of mitral valve demands precise and sophisticated imaging
      during any intervention .Transesophageal echocardiography has been the most
      frequently used modality. With the advent of three-dimensional echocardiography a
      more comprehensive description of the mitral valve is now possible. This review
      aims to discuss the framework for imaging the mitral valve by three-dimensional
      echocardiography; its current status and the limitations of three-dimensional
      echocardiography in its current platform.

PMID- 22616340
TI  - Left ventricular pseudoaneurysm.

PMID- 22616341
TI  - Intestinal lymphangiectasia in a patient with autoimmune polyglandular syndrome
      type III.
AB  - Autoimmune polyglandular syndromes (APS) comprise a wide clinical spectrum of
      autoimmune disorders. APS is divided into Type I, Type II, Type I and Type IV
      depending upon the pattern of disease combination. Ghronic diarrhoea is one of
      the many manifestations of APS and many aetiological factors have been suggested
      for it. Apart from the established aetiological factors, intestinal
      lymphangiectasia may be responsible for chronic diarrhea in some cases.Intestinal
      lymphangiectasia has been reported in Type I APS. We report a case of Type III
      APS with hypocalcaemia and hypothyroidism who had chronic diarrhea of long
      duration and was finally diagnosed to have intestinal lymphangiectasia.

PMID- 22616342
TI  - Acute pancreatitis in a case of falciparum malaria--a rare presentation.
AB  - Various complications including multiorgan failure is not uncommon in Falciparum
      malaria. But acute pancreatitis is a very rare complication in falciparum
      malaria. We describe here such a patient who suffered from acute pancreatitis and
      multiorgan failure.

PMID- 22616343
TI  - Unilateral and painless development of isoniazid induced gynecomastia during re
      treatment of pulmonary tuberculosis.
AB  - A case of isoniazid induced gynecomastia is being reported in an 18-year old
      male, who received a re-treatment regimen for the relapse of pulmonary
      tuberculosis (TB). At the end of two months of the treatment, the patient
      developed a painless unilateral gynecomastia, which completely disappeared after
      a month of the cessation of isoniazid. A review of literature on isoniazid
      induced gynecomastia is discussed.

PMID- 22616344
TI  - Hypokalemic periodic paralysis due to proximal renal tubular acidosis in a case
      with membranoproliferative glomerulonephritis.
AB  - Proximal renal tubular acidosis (pRTA) is a rare disorder. Hypokalemia may be
      associated with it; occasionally leading to features like hypokalemic periodic
      paralysis. Though pRTA is a tubulointerstitial kidney disease, glomerulonephritis
      may occasionally lead to pRTA by tubular damage through leaking proteins,
      cytokines or by inflammatory infiltrates. In our reported case a 27 year old male
      had recurrent episodes of hypokalemic quadriparesis. Investigations revealed
      features of pRTA including hypokalemia and non-anion-gap hyperchloremic metabolic
      acidosis. His urine pH dropped to 5 with NH4Cl loading test. Kidney biopsy showed
      membranoproliferative glomerulonephritis with tubulointerstitial damage.
      Hypokalemic periodic paralysis and pRTA are uncommon associations of
      membranoproliferative glomerulonephritis.

PMID- 22616345
TI  - An interesting case of cardiotoxicity due to bufotoxin (toad toxin).
AB  - Consumption of toads for their aphrodisiac effect is a common practice in Laos,
      China and in some parts of India. Toad secretions from parotid and skin contains
      toxin similar to cardiac glycosides. It results in bradycardia and cardiac
      dysfunction leading on to death in some cases. We report a case of toad poisoning
      in a young previously healthy male.

PMID- 22616346
TI  - A case of primary ciliary dyskinesia with pulmonary arterial hypertension
      responding to oral sildenafil.
AB  - Primary ciliary dyskinesia (PCD) is an autosomal recessive heterogeneous group of
      conditions with variable clinical findings like recurrent respiratory tract
      infections, bronchiectasis, situs inversus, singly or in various combinations.
      Development of Pulmonary arterial hypertension can be a late complication of this
      disease. Here we present a case of PCD with recurrent respiratory tract
      infections, bronchiectasis and severe PAH, who responded to treatment with
      Oxygen, IV broad spectrum antibiotics and oral sildenafil.

PMID- 22616347
TI  - Deep vein thrombosis and euvolemic hyponatremia in a hypothyroid patient.
AB  - Hypothyroidism is a procoagulant state; hypothyroid females have greater risk of
      DVT than hypothyroid males. We present a case of primary hypothyroidism who
      presented with euvolemic hyponatremia and DVT that required thyroxine replacement
      and correction of hyponatremia. This highlights that hypothyroidism can present
      as euvolemic hyponatremia and deep vein thrombosis.

PMID- 22616348
TI  - Brown-Sequard & his syndrome.

PMID- 22616349
TI  - Emerging role of DPP-4 inhibitor Vildagliptin in the management of type-2
      diabetes.

PMID- 22616350
TI  - Osseous hydatid cyst.

PMID- 22616351
TI  - Getting on with the job.

PMID- 22616352
TI  - Opening up the 'black box' of the electronic patient record: a linguistic
      ethnographic study in general practice.
AB  - One of the most pervasive changes in general practice is the introduction of the
      electronic patient record (EPR). The EPR supports both immediate clinical and
      anticipatory care (e.g. management of risk factors). Incorporating the EPR into
      social interaction is a complex task which is achieved discursively, clinician
      and patient responding to interactional contingencies as the consultation
      unfolds. Clinicians are presented with a 'dilemma of attention' as they seek to
      deal with the immediacy ('here and now') of the interpersonal interaction and the
      institutional demands ('there and then') of the EPR. We present data analysis
      which illuminates the EPR as an important presence in the clinic consultation
      context, one which places material and textual demands. Developing previous work
      on the triadic (three party) consultation, our novel multimodal analysis of the
      EPR-in-use suggests there is value in considering the EPR as a collection of
      silent but consequential voices. Micro-analytic attention to the way in which
      these different voices are managed, combined with understandings drawn from
      ethnographic observation of the primary care context, reveals the EPR as
      exhibiting a previously under-explored kind of 'agency' within the consultation.

PMID- 22616353
TI  - Patients' narratives of chronic illnesses and the notion of biographical
      disruption.
AB  - Bury's (1982) argument that the onset of a chronic illness represents a
      biographical disruption has become paradigmatic in the sociology of illness
      studies. More recently Bury (1991, 1997) himself Williams (2000) and other
      medical sociologists have argued that the notion of illness as biographical
      disruption needs re-examination. Following a phenomenological approach, in this
      paper the author draws on different narrative models (Labov and Waletzky 1967 and
      Ricoeur 1980) to analyze how patients orient to the onset of chronic illness as
      the complicating action. The data comprise eight narratives collected in South
      America: three correspond to patients with renal failure, and five to patients
      with HIV/AIDS disease. It is observed that in some cases, patients' complicating
      actions are rather oriented to experiences of poverty, drug addiction, and
      criminality that took place prior to their onset of their illnesses. These
      experiences, instead of the onset of their illnesses, occupy the place of the
      complicating action in these patients' narratives. The author discusses that in
      the studies of illness narratives, it is difficult to operate from a different
      paradigm, but argues that conflating the onset of chronic illness with a
      biographical disruption may confuse the episodic dimension of narrative with the
      configurational dimension.

PMID- 22616354
TI  - Interdisciplinary research on patient-provider communication: a cross-method
      comparison.
AB  - Patient-provider communication, a key aspect of healthcare delivery, has been
      assessed through multiple methods for purposes of research, education, and
      quality control. Common techniques include satisfaction ratings and
      quantitatively- and qualitatively-oriented direct observations. Identifying the
      strengths and weaknesses of different approaches is critically important in
      determining the appropriate assessment method for a specific research or
      practical goal. Analyzing ten videotaped simulated encounters between medical
      students and Standardized Patients (SPs), this study compared three existing
      assessment methods through the same data set. Methods included: (1) dichotomized
      SP ratings on students' communication skills; (2) Roter Interaction Analysis
      System (RIAS) analysis; and (3) inductive discourse analysis informed by
      sociolinguistic theories. The large dichotomous contrast between good and poor
      ratings in (1) was not evidenced in any of the other methods. Following a
      discussion of strengths and weaknesses of each approach, we pilot-tested a
      combined assessment done by coders blinded to results of (1)-(3). This type of
      integrative approach has the potential of adding a quantifiable dimension to
      qualitative, discourse-based observations. Subjecting the same data set to
      separate analytic methods provides an excellent opportunity for methodological
      comparisons with the goal of informing future assessment of clinical encounters.

PMID- 22616355
TI  - Combining interdisciplinary and International Medical Graduate perspectives to
      teach clinical and ethical communication using multimedia.
AB  - In Australia, international medical graduates (IMGs) play a crucial role in
      addressing workforce shortages in healthcare. Their ability to deliver safe and
      effective healthcare in an unfamiliar cultural setting is intrinsically tied to
      effective communication. Hospital-based medical clinical educators, who play an
      important role in providing communication training to IMGs, would benefit from
      practical resources and an understanding of the relevant pedagogies to address
      these issues in their teaching. This paper examines the nature of an
      interdisciplinary collaboration to develop multimedia resources for teaching
      clinical and ethical communication to IMGs. We describe the processes and
      dynamics of the collaboration, and outline the methodologies from applied
      linguistics, medical education, and health ethics that we drew upon. The
      multimedia consist of three video clips of challenging communication scenarios as
      well as experienced IMGs talking about communication and ethics. The multimedia
      are supported by teaching guidelines that address relevant disciplinary concerns
      of the three areas of collaboration. In the paper's discussion we point out the
      pre-conditions that facilitated the interdisciplinary collaboration. We propose
      that such collaborative approaches between the disciplines and participants can
      provide new perspectives to address the multifaceted challenges of clinical
      teaching and practice.

PMID- 22616356
TI  - Promissory accounts of personalisation in the commercialisation of genomic
      knowledge.
AB  - As part of personalised medicine emerging from the human genomics revolution,
      many websites now offer direct-to-consumer genetic testing. Here, we examine
      three personal genomics companies--Navigenics, deCODEme and 23andMe--each of
      which represents contrasting registers of 'personalisation'. We identify three
      distinctive registers in these websites: a paternalistic (medical) register; a
      translational (scientific) register and a democratic (consumerist) register. We
      explore in detail the rhetorical and discourse devices employed in these websites
      to assess how personalised healthcare is promised to the public. Promising
      information that will empower prevention of common complex diseases and ensure
      better quality of life is conflated with promising greater access to personal
      information. The presence and absence of scientific legitimacy is related to
      concerns about accuracy and validity on the one side, and fears of paternalism
      and elitism on the other. Nevertheless, a common strategy uniting these different
      styles of personalisation is consumer empowerment. Finally, we consider the
      tension between the drive of translational medicine to make human genomic
      research practically relevant, and the intrinsic uncertainties of scientific
      research and show how, in the commercial domain, future risks are transformed
      into discourses of promise by concealing these uncertainties.

PMID- 22616357
TI  - The persuasive role of ethos in doctor-patient interactions.
AB  - In 'expert-to-non-expert' interactions, one of the distinguishing features is
      that there is no or very little shared knowledge between the subjects. This
      situation may become particularly challenging when the unshared knowledge is of a
      very technical kind, as the likeliness of misunderstandings or unsuccessful
      communication becomes very high. This is particularly true of interactions
      between patients and physicians. In the course of such interactions, physicians
      are expected to inform, advise and persuade patients regarding their health
      problems. It is especially when differences of opinion emerge that physicians
      need to be persuasive, but it is also then that this may become very difficult,
      as the patient does not share the medical expertise of the physician. At these
      moments, one of the most powerful means of persuasion in the hands of physicians
      is their professional ethos, or authority. The paper presents partial results of
      an ongoing research project aimed at describing the ways in which physicians
      construct their professional ethos in interactions with their patients, and how
      they use it to reconcile patients' diverging opinions with their own. The
      analysis is carried out on a corpus of video recordings of doctor-patient
      interactions and it is aimed at identifying different persuasive strategies based
      on the professional ethos.

PMID- 22616358
TI  - 'Sometimes you've just got to have fun, haven't you?': The discursive
      construction of social drinking practices in young adults' accounts of chronic
      illness.
AB  - Social drinking practices have been found to be a salient issue for young adults
      suffering from type 1 diabetes (T1DM), and inflammatory bowel disease (IBD), with
      many reporting participating in such practices in spite of the potential
      additional health risks (Eaton et al. 2001; Balfe 2009). Drawing on interviews
      with sufferers of T1DM and IBD, aged 18-29 (n = 30), this paper aims to
      investigate how their reasoning behind this behaviour is discursively
      constructed. Through using the 'Accounts' framework (Scott and Lyman 1968),
      sufferers were shown to construct an identity of 'good' diabetic, or IBD,
      sufferer. A key difference found across the two conditions was that T1DM
      sufferers more regularly constructed 'excuses' for engaging in potentially
      'risky' behaviour, whereas IBD sufferers predominantly produced 'justifications'
      which framed their behaviour as not necessarily being irresponsible. This finding
      reflects the degree of risk at which sufferers of the respective conditions view
      their social drinking behaviour as placing them. The stronger biomedical evidence
      that alcohol has negative effects on T1DM leads sufferers to view their 'healthy
      body' (Balfe 2009) in terms of more serious health implications, whereas IBD
      sufferers view their 'healthy body' in terms of short-term exacerbation of
      symptoms, which they do not see as significantly affecting their general IBD
      health.

PMID- 22616359
TI  - An exploratory study of how trust in health care institutions varies across
      African American, Hispanic and white populations.
AB  - BACKGROUND: Minority and non-minority patients in the United States have
      different levels of trust in health care; however, few studies have examined how
      determinants of trust and distrust in health care vary across diverse groups.
      OBJECTIVE: To explore how trust in health care institutions varies across diverse
      populations. METHODS: We conducted 17 focus groups with 117 participants in
      Chicago: 9 with African American, 5 with Hispanic, and 3 with white participants.
      Discussions were audiotaped, transcribed verbatim and coded using grounded theory
      analysis to identify dominant themes. RESULTS: We found a core set of factors
      that contribute to trust and distrust across racial/ethnic groups. In addition,
      there were unique factors that contributed to distrust among African Americans
      and Hispanics. Both of these groups discussed expectations of discrimination in
      the health care setting and African Americans discussed expectations of being
      experimented on as determinants of distrust. Based on these findings, we
      developed a hypothetical model of how different factors influence trust and
      distrust in health care across these different racial/ethnic groups. CONCLUSIONS:
      Contributors to trust and distrust in health care institutions are not always
      uniform across racial/ethnic groups. These differences should be addressed in
      future research and efforts to enhance trust in health care institutions.

PMID- 22616360
TI  - What to eat in the land of cheese and chocolate: a content analysis of Swiss
      print media messages on a healthy diet.
AB  - This paper describes a specific coding scheme for measuring health-related media
      content on the level of single assertions and in relative complexity. The basic
      idea is to code messages into an if-part (nutrition, physical activity, body
      weight) and a then-part (weight and health). Detailed codeplans can then be used
      to determine the specific nature of the if- and then-parts of an assertion. An
      exemplary analysis of Swiss-German newspaper and magazine messages between March
      1, 2003 and June 30, 2005 provides evidence of recommendations that are more or
      less in line with official suggestions for a healthy diet: Newspapers and
      magazines tell their readers to eat vegetables, fruit, grain and cereal products,
      dairy products, and to care about vitamin and minerals intake. They also advise
      to stay away from tobacco, alcohol, fast food, sugar, and animal fat. Results are
      interpreted as evidence for the existence of a rather good source for diet
      information in print media, which is, however, very likely to be counteracted by
      other media content.

PMID- 22616361
TI  - [Aging nurses. Reorganizing work to retain nurses].
AB  - The nurse population is growing old in most occidental countries. Facing the
      physical and psychological loud of their job, many nurses aspire to get retired
      before the legal age. Such a process is likely to increase the present nursing
      shortage and so to endanger the care access for a part of the population.
      Different concepts such the Work ability or the Age management have been
      developed to allow a better response the professionals' needs. Their offer models
      and tools to redesign the work organization in a way so that nurses would be able
      to stay at work in good conditions. These approaches require nevertheless a real
      political and organizational willingness.

PMID- 22616362
TI  - [First elements for a phenomenology of suffering].
AB  - The context of emergence of the theme of the professional suffering requires the
      research of means to understand the notion of "suffering" and to act. In this
      sense, the phenomelogical pratice displays a method to lead our glance to the
      concrete phenomenon felt by the suffering Self, in closer of his alive experience
      and innermost sense. This method, made of suspension of the judgment, of
      reflexive conversion and of eidetic variation, helps to obtain an other quality
      of knowledge than the knowledge obtained by the objectivized procedures. Thus, we
      find several prominent dimensions of the phenomenal suffering: the passivity, the
      interlacing and the uncertainty, among others. This "man level" approach may
      interest the professionals in the jobs of the relations, especially in the caring
      sector, with the double aim of the accompaniment of the suffering and of the
      resistance against the growing professional suffering.

PMID- 22616363
TI  - [The association between the patient-nurse relationship and patient perception of
      substance use control in an addiction therapy setting: a descriptive correlation
      study].
AB  - The aim of this study is to explore the association between the patient-nurse
      working alliance and the degree of how much substance use control is perceived as
      burdensome in an addiction therapy setting. Imogene King's theory and the working
      alliance concept were used as the theoretical framework. The investigation was
      undertaken using a self-administered questionnaire with the short-form of the
      working alliance inventory (WAI) translated and validated in French and targeting
      a convenience sample (n=28). In this sample the working alliance was evaluated by
      12 questions on a Likert-Scale and perceived as generally good (x = 61.68, max =
      84). A significant negative linear relation was found between the perception of
      the drug-controls as burdensome, evaluated by an additional question on a visual
      analogue scale (VAS), and the establishment of a working alliance (r = -0.67, p
      value > 0.001). Furthermore, the form of admission is important as involuntarily
      hospitalized patients (n = 7) (t, p-value = 0.018) form poorer working alliances,
      and perceive the controls as more burdensome (Z, p-value = 0.004) as opposed to
      voluntarily hospitalized patients (n = 21). Even though these results cannot be
      generalized because of the small sample (n = 28), they raise important questions
      for nursing practice, especially for involuntarily hospitalized patients. These
      patients seem to be more susceptible to any disturbance of the relationship and
      possible consequences need to be taken into account. In addition, drug-control
      might have to be reassessed. The findings also raise questions about the use of
      camera supervision as an alternative to nursing supervision and about the need
      for the primary nurses to refrain from control interventions.

PMID- 22616364
TI  - [Participation of healthcare staff and nurse autonomy for HIV/AIDS screening].
AB  - A study on rapid routine HIV screening was mainly performed by nurses in 29
      Emergency departments (EDs) of Paris urban area. Individual and collective
      covariates of healthcare staff participation were analyzed, along with
      positioning regarding the nurse autonomy for this activity. International studies
      confirm the interest of nurse screening. 25 interviews with nurses, nurse
      supervisors and physicians were performed in 5 departments. The staff
      participation is associated with motivation for HIV or prevention, a
      multidisciplinary approach, a generalist background or short professional
      experience, as well as the perception of an easy process. Most of nurses
      succeeded in offering, realizing the test and disclosing the negative results to
      patients. This activity was considered as an autonomy vector. After training
      sessions, HIV screening could become part of the nurse mandate of prevention in
      collaboration with physicians. This collaboration addresses a classic work
      division for nurse supervisors and doctors. However, a systematic implementation
      of HIV screening in EDs seems not to be executable because of structural
      constraints. The autonomy for nurse-initiated HIV screening enlarged to
      prevention and public health activities is positively considered by nurses.

PMID- 22616365
TI  - [Professional values: a strategic component of health professionals. The
      contribution of decisional research at the Toulouse University Hospital Center].
AB  - The organizational involvement concept is often developed by many researchers and
      practitioners. This study is in the right inheritance of Allen and Meyer (1990)
      and Thevenet and Neveu (2002) works who all considered the involvement as "an
      affective or emotional attachment towards the organization such as an individual
      strongly involved identifies himself, reinforces his own agreement and enjoys
      being a member of the organization that employs him". The aim of this study was
      to demonstrate the impact of professional values (in terms of adherence to the
      purposes, norms and values of the establishment upon the subject's involvement in
      professional activities). 1538 health professionals practising in Toulouse
      academic hospital center have answered a questionnaire upon the subject's
      individual perception of his personal involvement in his workplace; the possible
      working impacts upon his own motivation, the perceptions upon professional
      values. Results indicate that if involvement is subject to professional values,
      it turns towards a double determination: technical and axiological or ethical.
      The professional and axiological dimension introduces a moral position and a
      cognitive framework that participates in the decision-making action : working
      together, creating a climate of confidence, trusting the group, and progressing
      for greater cohesion. The ethical dimension joins historic and humanist values:
      self respect and altruism; developing human values for oneself and for others.
      Specifying values is already a project in itself, in terms of consciousness.
      Understanding those impacts upon health professionals involvements' is also the
      aim to include the historical of our Care Project in collective interaction,
      alteration and construction purposes.

PMID- 22616366
TI  - [Competence in and uses for information technology at the Training Institute in
      Nursing].
AB  - After the presentation of three references to Information and communication
      technology (ICT) skills, the capacity of trainers training institute in nursing
      are explored through a survey of opinion. The use in the professional practice of
      these skills is captured by a dichotomous terms question.

PMID- 22616368
TI  - [A synthesis of patient problems: a first step to the nursing minimum data set].
AB  - In 2012 Switzerland will adopt a system for hospital funding, named SwissDRG,
      based on the German Diagnosis Related Group model. This method of funding takes
      little account of nursing as the grouping is based on diagnoses and treatments.
      OBJECTIVE: This study conducted at the University Hospital of Lausanne seeks to
      introduce nursing data in the medical statistic under the form of diagnosis.
      METHOD: Based on a web questionnaire, this study interviewed 293 nursing clinical
      and administrative managers. According to their experience they had to selected
      10 problems of care from a list of 30 and sort them depending to their impact on
      the workload and length of stay. RESULTS: 95 responses from most of the clinical
      specialties of the University Hospital of Lausanne. A list of 15 nursing problems
      has been published. The use of the RIDITs shows a difference between the
      subgroups determined by sex and length of service. CONCLUSION: This study showed
      that the use of web questionnaires is a way that should be continued. It also
      shows that through the RIDITs it is possible to analyze the differences in
      responses between groups even if the sample is small. This study must now be
      extended to the pediatrics and obstetrics.

PMID- 22616367
TI  - [Postprandial blood pressure drop in hemodialysis: myth or reality?].
AB  - The meal is a friendly moment of the sessions of dialysis, appreciated by most of
      the dialysed persons. However the empirical observation allows to notice that
      certain dialysed persons, present drops of arterial pressure after taking the
      meal. Where from the questioning: except factors inherent to the dialysis, has
      the meal a particular incidence on the blood pressure in the course of session?
      Numerous studies were realized since 1983 on the low blood pressure comment
      prandiale at the old person, very few studies are available on the low blood
      pressure comment prandiale in the course of session of hemodialysis, and
      sometimes little convincing. A comparative method on 2 sessions, one with meal
      and one without meal, every patient being its own witness, was used. The tool of
      evaluation consists of a railing resuming variables retained for the study. In
      view of the study carried out further to this questioning, the hypothesis of
      departure does not come true: we cannot demonstrate of significant link between
      meal and arterial pressure drop. However the number restricted by patients
      (fifty) include in the study, does not allow us to end in favour of the myth, it
      is necessary for it to pursue the study to obtain the same data with a much more
      important population.

PMID- 22616369
TI  - [Inside the French reform of nursing education: a survey of faculty members].
AB  - Changing societal health care needs has led the Ministry of Health to rethink the
      paramedical courses. European harmonization was needed to set up this training
      with the LMD system within a university scheme. Based on this new paradigm, an
      educational reform consisting of a competency-based approach was implemented,
      leading to major modifications in the function of a trainer. Consequently,
      training institutes for health care managers had to adapt their program to this
      new learning concept. The main objective of this study was to identify the needs
      of trainers in charge of this new graduate nurse program. The secondary objective
      was to collect their perceptions in order to recognize the positive or negative
      factors related to these changes. A questionnaire survey was conducted with 276
      trainers belonging to 16 out of the 17 nursing schools of the Rhone-Alpes 2
      region. One hundred and five trainers responded, corresponding to a rate of 38%.
      The majority of the respondents considered the new program as suitable, both for
      training and for profession. The skills approach is seen as a factor for
      improvement. The learnings to be developed are in line with reflective practice
      and the conception of symbolic situations. The study has allowed to gather the
      needs for the trainers to adapt their training. It highlighted the importance of
      a referent trainer for the trainee, a major and precious lever for change.

PMID- 22616370
TI  - [Albert Bandura and his work].
AB  - The Canadian psychologist Albert Bandura (1925) author of the concept of self
      efficacy is still not much known of nurses. This article offers an outline of his
      biography and his work. Theories of Albert Bandura provide a positive, dynamic
      relationship with the agentivity human control over events that affect their
      existence. The concept of vicarious learning, self-efficacy and agency can enrich
      nursing research.

PMID- 22616372
TI  - [Statin therapy--for whom?].
AB  - For patients with cardiovascular disease, statins belong to routine medical
      treatment irrespective of blood lipid levels. In primary prevention also, statins
      have been found to prevent cardiovascular diseases, associated deaths and
      decrease overall mortality. In previously healthy persons the use of statins
      should be based on the assessment of total risk--mere cholesterol level does not
      usually constitute an indication for treatment. The use of statins may lead to
      adverse effects, the major one being myopathy, for which an elevated risk is
      associated with increasing statin dosages.

PMID- 22616371
TI  - [Is it necessary to monitor the cognitive development of a child having
      diabetes?].
AB  - Metabolic disorders associated with type 1 diabetes may affect brain function
      both momentarily during excessively low or high blood glucose levels and by
      causing permanent alterations. These may have an influence on the cognitive
      development of a child who has been diagnosed with diabetes at a very young age.
      Significant learning problems are rare, but their early detection and appropriate
      support are part of good clinical practice. Good glucose control protects also
      the brain.

PMID- 22616373
TI  - [Paroxysmal feeling of suffocation during sleep--a diagnostic challenge].
AB  - Our patient suffered from nocturnal awakenings due to paroxysmal feelings of
      suffocation for three years. He was extensively examined at the community health
      centre and at the departments of neurology, psychiatry, oral diseases and
      respiratory medicine of the district hospital and the university hospital. The
      clinical hunch of the night nurses of the department of respiratory medicine and
      video EEG monitoring recommended by the sleep disorders team eventually revealed
      the real cause of the patient's symptoms.

PMID- 22616374
TI  - [Group A streptococcal pneumonia].
AB  - Group A betahemolytic streptococcus may cause a severe pneumonia that is
      accompanied by septic shock and multiorgan failure. The disease is rare and may
      develop slowly and thus the diagnosis and the most efficient treatment may be
      delayed. We describe two children and two adults with pneumonia and toxic shock
      syndrome caused by group A streptococci. All patients needed ventilator
      treatment. In addition to other antibiotics clindamycin, that restrains toxin
      production by group A streptococci, was administered to three of the patients.
      All patients had a full recovery, but one patient developed optic neuropathy and
      lost his vision.

PMID- 22616375
TI  - [Update on current care guidelines: sore throat].
AB  - Sore throat (pharyngitis) is typically a viral infection. Patients should be
      informed that pharyngitis is usually a mild, self-healing disease. Throat swab is
      recommended for adults with two or more symptoms: fever over 38 degrees C,
      swollen submandibular lymph nodes, tonsillar exudate and no cough. Children under
      15 years of age with any of these symptoms should be tested. If antibiotic is
      indicated, penicillin is the preferred choice, whereas first generation
      cephalosporins are recommended for those with penicillin allergy. Antibiotics can
      be started for patients with high fever before culture results are available.
      Adequate pain medication is important.

PMID- 22616376
TI  - [Infertility and risk of cancer].
AB  - Ovulation problems, ovarian endometriosis and impaired sperm quality may be
      factors underlying infertility and possibly predisposing to cancer diseases.
      Infertility therapies utilize products that alter the hormonal balance and may in
      theory increase the risk of cancer. Handling of gametes in the laboratory is also
      likely to influence gene regulation. Ovulation induction therapies may increase
      the risk of uterine cancer, and in vitro fertilization (IVF) therapies may
      increase ovarian tumors. Children born after IVF therapies seem to have a
      statistically elevated risk of cancer. Instead of risk ratios, the use of clear
      figures is recommended in patient information.

PMID- 22616377
TI  - [Effects of cancer treatments on gonads].
AB  - High dose cytotoxic drug combinations as well as radiotherapies to the whole
      body, the pelvic region and the head ovarian are associated with a risk of
      gonadal damage. In men, cells responsible for sperm production are most prone to
      damage, but testosterone production is usually preserved. In women, cancer
      treatments are known to accelerate the disappearance of primordial follicles,
      prevent ovarian follicle growth and increase fibrosis. This decreases the non
      regenerable pool of oocytes. In young women, the ovaries may function well
      shortly after cancer treatments, whereby getting pregnant is possible. However
      they are in inreased risk of premature menopause.

PMID- 22616378
TI  - [Reproductive health after cancer treatment--contraception, planning and
      monitoring of pregnancy].
AB  - Infertility is common after cancer treatments, but pregnancies of those treated
      for cancer usually proceed well. Pretreatment counseling by a fertility doctor
      improves posttreatment quality of life. The most important issues to be
      considered in pregnancy planning and monitoring include cytotoxic drug induced
      organ-specific insufficiencies and radiotherapy targeted at the thoracic region,
      whole body, or at the uterus during childhood. Hypothyroidism is the most common
      hormonal complication and is also significant with respect to fertility and
      gravidity.

PMID- 22616379
TI  - [Cancer diagnosed during pregnancy].
AB  - The risk of contracting cancer is approximately 1 out of 1,000 pregnancies. The
      most common types of cancer include melanoma, cervical cancer and breast cancer.
      Utilization of MRI studies for radiological examination of cancer during
      pregnancy is recommended. Mammography and chest radiography are also allowed.
      Computed tomographic scanning of the abdominal region should be avoided. The
      prognosis during pregnancy is dependent on the extent and histologic type of the
      cancer. Chemotherapy can be started after the first trimester of pregnancy and
      terminated about one month before delivery.

PMID- 22616380
TI  - [The health of children born after cancer treatments].
AB  - With the development of cancer treatments an increasing number of patients having
      contracted cancer at a young age will survive. Those who have recovered from
      cancer will, however, have children almost twice more infrequently than their
      siblings. Women who have received radiotherapy especially in the abdominal and
      pelvic region possess an increased risk of premature delivery. Progeny of the
      patients have been shown not to possess an increased risk of intrauterine death,
      death during the neonatal period or embryonic deaths. According to current
      knowledge, cancer treatments do not have transgenerational effects and do not
      increase the risk of cancer among the progeny.

PMID- 22616381
TI  - [Mature eggs from primordial follicles in vitro--a challenge in the near future].
AB  - In vitro maturation of eggs from frozen-preserved tissue would be an important
      infertility therapy for women, whose eggs have been destroyed during cancer
      treatment. If there is a risk of presence of malignant cells in the tissue, it
      cannot be transferred back to the woman. Almost full-sized eggs are obtained in
      ovarian tissue culture by abolishing inhibition of the activation of ovarian
      follicles and by adding growth-regulating growth factors and hormones. Their
      final maturation in the subsequent culture and fertilization will hopefully be
      successful in the near future.

PMID- 22616382
TI  - Two dreams.

PMID- 22616383
TI  - How should we model rare disease allocation decisions?

PMID- 22616384
TI  - Too much information?

PMID- 22616385
TI  - Too much information?

PMID- 22616386
TI  - Too much information?

PMID- 22616387
TI  - Too much information?

PMID- 22616388
TI  - Doctors and torture.

PMID- 22616389
TI  - Dr. Douchebag: a tale of the emergency department.

PMID- 22616390
TI  - What law really requires.

PMID- 22616391
TI  - Fees can't build good fences.

PMID- 22616392
TI  - Case study. Undocumented patients.

PMID- 22616393
TI  - Undocumented patients. Commentary.

PMID- 22616394
TI  - Undocumnted patients. Commentary.

PMID- 22616395
TI  - Conceived and deceived: the medical interests of donor-conceived individuals.

PMID- 22616396
TI  - The ghosts of institutionalization at Pennhurst's haunted asylum.

PMID- 22616397
TI  - The outsider.

PMID- 22616398
TI  - Which orphans will find a home? The rule of rescue in resource allocation for
      rare diseases.

PMID- 22616399
TI  - Reasonable disagreement about identified vs. statistical.

PMID- 22616400
TI  - Should we call it fraud?

PMID- 22616401
TI  - Assuring the future of nursing education.

PMID- 22616402
TI  - The PNAA Nurse Balik Turo: return to the homeland to give back and teach.

PMID- 22616403
TI  - Nurse preceptors' views of precepting undergraduate nursing students.
AB  - The nurse preceptor is an essential bridge between the classroom and the real
      world of human patients and clinical settings. The 26 experienced nurse
      preceptors who participated in this qualitative study shared stories and
      important perspectives on the nurse preceptor role in pre-licensure nursing
      education. Three consistent themes emerged: being engaged in the educational
      process, acknowledge my efforts, and it depends on the student. These findings
      have implications for schools of nursing and faculty working with undergraduate
      students in the clinical setting.

PMID- 22616404
TI  - Nurses' attitudes toward continuing formal education: a comparison by level of
      education and geography.
AB  - The education of nurses has an influence on patient safety and outcomes, the
      nursing shortage, the faculty shortage, and nurses' attitudes and actions. This
      article reports on a dissertation study designed to examine the attitudes of
      nurses, initially registered with an associate degree or diploma in nursing,
      toward continuing formal education. Actively licensed registered nurses in the
      eastern and western United States (n=535) participated. The main finding of this
      study was that, although nurses held positive attitudes overall, attitudes ranked
      barely above neutral. The findings suggest that work needs to be done to improve
      nurses' attitudes toward continuing formal education and research needs to be
      undertaken to understand what would entice nurses back to school. Implications
      for nursing practice and education are discussed along with suggestions for
      future research.

PMID- 22616405
TI  - Assessing outcomes of a study abroad course for nursing students.
AB  - There is little debate about the importance of preparing nursing graduates to
      provide culturally sensitive care to an increasingly diverse society. However, it
      is difficult for nurse educators to fit learning experiences that help students
      develop cultural competence into already full programs and create mechanisms to
      evaluate the results. This article describes a study to assess the impact of a
      study abroad program on developing cultural competence, including cultural
      awareness, sensitivity, knowledge, and skills. Results from the Cultural
      Awareness Survey, reflective journals, and interviews illustrate how the study
      abroad experience influenced the development of components of cultural competence
      and might influence clinical practice. Results suggest effective teaching
      strategies to assist students in becoming culturally competent are experiential
      in nature and include role modeling, reflective activities, and group discussion.

PMID- 22616406
TI  - Bilingual nurse education program: applicant characteristics that predict
      success.
AB  - Nurses are in great demand across the United States, but those fluent in both
      Spanish and English are in particularly short supply. This study examined three
      cohorts of students that entered a Spanish-English nursing education program to
      determine characteristics of applicants that produced student success. Unlike
      many nursing programs, entrance requirements for this bilingual program did not
      include a minimal grade point average (GPA) or previous course completions.
      Logistic regression was used to analyze the relationship between five different
      characteristics of entering students and their later success in the program.
      Success was measured in terms of program persistence and performance on the NCLEX
      PN and NCLEX-RN exams. Incoming students with relatively high GPAs (M = 3.2) were
      significantly more likely to persist through the entire nursing 0ronram and oass
      the NCLEX-RN exam (t < .05) than those with lower GPAs (M = 2.5).

PMID- 22616407
TI  - Reflective journaling and development of cultural humility in students.
AB  - Cultural humility requires self-evaluation and the awareness that one's own
      culture is not the only or best one. Teaching health care providers to become
      culturally humble includes the development of critical thinking skills and the
      ability to reflect on practice. Journaling as a teaching strategy helps students
      develop these skills. This article describes the use of reflective journaling as
      students progressed through four semesters of a community clinical experience.
      This qualitative, descriptive study was based on the principles of naturalistic
      inquiry with person-centered written reflections.Two hundred journal entries from
      50 students were reviewed, and II themes were identified. Cultural humility
      cannot be learned merely in the classroom with traditional teaching methods.
      Reflection on experiences over time leads to the development of cultural
      humility.

PMID- 22616408
TI  - "Me and my computer": emotional factors in online learning.
AB  - This study focused on nursing student perceptions of sense of community in the
      online classroom. Using qualitative analysis of data gathered from five student
      focus groups, themes related to the affective domain in online learning were
      identified: aloneness, anonymity, nonverbal communication, trepidations, and
      unknowns. This article provides detailed examples of student experiences under
      each theme and suggests that greater attention to the affective domain is needed,
      particularly in asynchronous online learning. Pedagogical strategies that foster
      a sense of community in online courses between students and faculty enhance
      cognition through affective engagement of students. Strategies for instructors
      are given.

PMID- 22616409
TI  - Teaching critical management skills to senior nursing students: videotaped or
      interactive hands-on instruction?
AB  - This study examined and compared the effectiveness of videotape training versus
      hands-on instruction in preparing senior nursing students to respond to emergency
      clinical situations. Fourth year nursing students (n=27) were randomly assigned
      to one of three groups; one group received videotaped instruction, one group
      engaged in a hands-on experience, and one group, a control, received no
      instruction. Students were evaluated using a three-station objective structured
      clinical examination that involved high-fidelity simulations. Differences between
      the control and the two instructional groups were significant (p = .007);
      however, there was no significant difference between the two types of
      instruction. It was concluded that instruction on crisis management with a high
      fidelity simulator, using either video or hands-on instruction, can result in a
      significant improvement in performance.

PMID- 22616410
TI  - Teaching home care electronic documentation skills to undergraduate nursing
      students.
AB  - Although there is general consensus that nursing students need knowledge and
      significant skill to document clinical findings electronically, nursing faculty
      face many barriers in ensuring that undergraduate students can practice on
      electronic health record systems (EHRS). External funding supported the
      development of an educational innovation through a partnership between a home
      care agency staff and nursing faculty. Modules were developed to teach EHRS
      skills using a case study of a homebound person requiring wound care and the
      Medicare-required OASIS documentation system. This article describes the
      development and implementation of the module for an upper-level baccalaureate
      nursing program located in New York City. Nursing faculty are being challenged to
      develop creative and economical solutions to expose nursing students to EHRSs in
      nonclinical settings.

PMID- 22616411
TI  - Development and evaluation of web-based animated pedagogical agents for
      facilitating critical thinking in nursing.
AB  - The purpose of this study was to evaluate the effectiveness of Web-based animated
      pedagogical agents on critical thinking among nursing students. A pedagogical
      agent or virtual character provides a possible innovative tool for critical
      thinking through active engagement of students by asking questions and providing
      feedback about a series of nursing case studies. This mixed methods experimental
      study used a pretest, posttest design with a control group. ANCOVA demonstrated
      no significant difference between the groups on the Critical Thinking Process
      Test. Pre- and post-think-alouds were analyzed using a rating tool and rubric for
      the presence of eight cognitive processes, level of critical thinking, and for
      accuracy of nursing diagnosis, conclusions, and evaluation. Chi-square analyses
      for each group revealed a significant difference for improvement of the critical
      thinking level and correct conclusions from pre-think-aloud to post-think-aloud,
      but only the pedagogical agent group had a significant result for appropriate
      evaluations.

PMID- 22616412
TI  - Interactive learning environment: engaging students using clickers.
AB  - Educators continue to search for effective methods that will engage students in
      their learning. This article presents the integration of clickers using the
      constructivist approach to foster critical thinking while engaging learners in a
      large classroom setting. A 22-item survey was used to measure the perceived value
      by students to the use of clickers in engaging them in the learning process and
      fostering critical thinking. Clickers, also known as personal response systems,
      created an interactive environment, moving students beyond simple recall to
      application, analysis, and construction of knowledge.

PMID- 22616413
TI  - On the horizon: what is new for 2012 and beyond? Part I.

PMID- 22616415
TI  - An Olympiad for public health?

PMID- 22616414
TI  - Collaborative interprofessional simulation in a baccalaureate nursing education
      program.

PMID- 22616416
TI  - Postcard from America.

PMID- 22616417
TI  - Peep into policy, politics, parliament.

PMID- 22616418
TI  - London 2012 construction project provides important lessons for improving health
      and safety in the construction industry.

PMID- 22616419
TI  - Paving the way.

PMID- 22616420
TI  - The financial crisis implications on the expected 2012 Olympics public health
      effect.

PMID- 22616421
TI  - London 2012.

PMID- 22616422
TI  - 'A Dance a Day'.

PMID- 22616423
TI  - Not all Olympic 'events' are good for the health just ask the previous occupants
      of the Manor Road Allotments.

PMID- 22616424
TI  - Promoting a healthy legacy for the Olympic Park: findings from a pre-games study.

PMID- 22616425
TI  - The contribution of informal logic to public health.

PMID- 22616426
TI  - Affirmation through disability: one athlete's personal journey to the London
      Paralympic Games.
AB  - AIMS: This article explores the personal narrative of a British Paralympic
      wheelchair tennis player who experienced a spinal cord injury (SCI) following a
      motorcycle accident in 2001 that left her paralysed from the waist down. The
      study responds to the call by Swain and French, among others, for alternative
      accounts of disability that demonstrate how life following impairment need not be
      empty and meaningless, but can actually reflect a positive, if different, social
      identity. METHODS: This study draws upon life history data to investigate the
      journey of one athlete who has managed to achieve international sporting success
      following a life-changing accident. A pseudonym has not been used for this study
      as the athlete wanted to be named in the research account and for her story to be
      shared. RESULTS: A chronological approach was adopted to map the pre- and post
      accident recovery process. The account examines life before the trauma, the
      impact of the accident, the process of rehabilitation and the journey to athletic
      accomplishment. CONCLUSIONS: Negative views of disability can be challenged if
      disability is viewed in the context of positive life narratives. The story of one
      Paralympian demonstrates how an 'ordinary' person has made the most of an
      extraordinary situation and become a world-class athlete. This paper demonstrates
      that in contrast to typical discourse in disability studies, becoming disabled or
      living with a disability need not be a tragedy but may on the contrary enhance
      life and lead to positive affirmation.

PMID- 22616427
TI  - Developing a physical activity legacy from the London 2012 Olympic and Paralympic
      Games: a policy-led systematic review.
AB  - AIMS: There is no evidence that previous Olympic Games have raised physical
      activity levels in adult populations. However, it may be premature to assume that
      this lack of previous evidence for an inherent effect is an indication that there
      is no potential to proactively harness the Games to generate a physical activity
      or sport legacy. Given that the political goal of achieving a physical activity
      legacy had already been set, the policy-led aim of this systematic review was to
      examine the processes by which the London 2012 Olympic and Paralympic Games might
      deliver a physical activity (as opposed to sport) legacy. METHODS: Searches were
      conducted on five databases: SPORTS DISCUS, CINAHL, PsychLNFO, MEDLINE and Web of
      Knowledge. RESULTS: There are two key findings: first, that communities that are
      not positively engaged with hosting the 2012 Games in London are likely to be
      beyond the reach of any initiatives seeking to harness the Games to develop
      legacies in any area; second, major events such as London 2012 can, if promoted
      in the right way, generate a 'festival effect' that may have the potential to be
      harnessed to promote physical activity among the least active. The 'festival
      effect' derives from the promotion of the 2012 Games as a national festival that
      is bigger than and beyond sport, but that is also rooted in the lives of local
      and cultural communities, thus creating a strong desire to participate in some
      way in an event that is both nationally significant and locally or culturally
      relevant. CONCLUSIONS: Physical activity policy makers and professionals should
      seek to satisfy this desire to participate through providing physical activity
      (rather than sport) opportunities presented as fun community events or
      programmes. The key to generating a physical activity legacy among the least
      active adults through this process is to de-emphasise the sporting element of the
      2012 Games and promote the festival element.

PMID- 22616428
TI  - Compliance of children in northern France with physical activity recommendations.
AB  - AIMS: This study examined the compliance of French children with physical
      activity (PA) guidelines, using objective assessments of PA. METHODS: The study
      involved 252 children aged 9.9 +/- 0.9 years, with mean height and weight of 1.39
      +/- 0.08 m and 35.8 +/- 8.8 kg, respectively. Their usual PA was evaluated during
      a week using an Actigraph accelerometer. RESULTS: The time spent in a moderate-to
      vigorous PA (MVPA) ranged from 142 +/- 44 min x d(-1) to 25 +/- 18 min/day
      according to the cut-offs used. Boys were significantly more active than girls (p
      < or = .001). Overweight/obese children spent significantly less time in MVPA as
      determined with cut-off points at 3200 cpm (-26%) or 3600 cpm (-35%) (p < .01).
      Between 5% (8% of boys vs 1% of girls, p < .0001) and 9% (14% of boys vs 3% of
      girls, p < .0001) of children probably met the PA guidelines. No relationships
      were found with socioeconomic status. CONCLUSIONS: This high proportion of
      insufficiently active children (> 90%), together with the relatively high
      proportion of overweight children in this area, advocates a more aggressive PA
      promotion project, which should target all children whatever their social
      origins.

PMID- 22616429
TI  - Exercise-, nature- and socially interactive-based initiatives improve mood and
      self-esteem in the clinical population.
AB  - AIMS: This study evaluated two existing group-based health promotion initiatives
      (a social club and a swimming group) and compared these to a new green exercise
      programme (weekly countryside and urban park walks). METHODS: Participants
      represented a clinical population (N = 53) and were all experiencing a range of
      mental health problems. They only attended one of the three programmes and
      sessions were held once a week for six weeks in all initiatives. Composite
      questionnaires incorporating two standardized measures to analyse changes in self
      esteem and mood were completed before and after all sessions. RESULTS: A
      significant main effect for self-esteem and mood pre and post activity (p <
      0.001) was reported after participating in a single session. The change in self
      esteem was significantly greater in the green exercise group compared with the
      social activities club (p < 0.001). Dose responses showed that both self-esteem
      and mood levels improved over the six-week period and improvements were related
      to attendance in the green exercise group. CONCLUSIONS: Green exercise as a
      health-promoting initiative for people experiencing mental ill health is equally
      as effective as existing programmes. Combining exercise, nature and social
      components in future initiatives may play a key role in managing and supporting
      recovery from mental ill health, suggesting a potential 'green' approach to
      mental healthcare and promotion.

PMID- 22616430
TI  - A short history of sheep scab.
AB  - The history of sheep scab is briefly discussed since it was first mentioned in
      180 BC. It was probably introduced to South Africa by the early settlers and was
      mentioned as a problem by Simon van der Stel, although its cause was only
      discovered in 1809. Various measures taken over the centuries to control or
      eradicate the disease, which has always been of considerable economic importance,
      are discussed, as well as the failures and reasons why it is still with us today.

PMID- 22616431
TI  - Veterinary education in South Africa: the classes of 1938 and 1939.
AB  - Concise descriptions are given of the life histories of the 10 members of the
      classes of 1938 and 1939. All of them initially joined the government service,
      Hugo, Steenekamp and Schatz spending their entire careers in the South African
      Veterinary (Field) Services. Mansvelt, the first recipient of the much-coveted
      Theiler medal, was the 2nd veterinarian to be appointed Director of Veterinary
      Services, a position specially created for the 'Field' in 1962. Having first
      established a successful private practice, Hofmeyr was appointed as the 1st full
      time professor of surgery of the Onderstepoort Faculty in 1958 and its 1st full
      time Dean in 1976. Albertyn opted for a career in public health, becoming
      director of 1 of the largest local municipal abattoirs. Turner spent virtually
      his entire career in private practice and was eventually joined by Brown who had
      served in the British Colonial Veterinary Service for many years. Fick was a
      government veterinarian for his entire career, first in South Africa, then in the
      British Colonial Service (for 13 years) and finally returning to South Africa.
      Like Hugo, Muller filled a senior position in veterinary (field) services before
      he opted for a farming career.

PMID- 22616432
TI  - Radiographic changes in Thoroughbred yearlings in South Africa.
AB  - This study involves the evaluation of pre-purchase radiographic studies of South
      African Thoroughbred yearlings. Radiographic changes were recorded and compared
      with similar international studies. The study differs from other studies in that
      a lower prevalence of pedal osteitis (1.26%), dorsal osteochondral fragmentation
      of the metatarsophalangeal joint (1.60%), distal metacarpal sagittal ridge
      changes (15.7%), ulnar carpal bone lucencies (8.33%), carpal osteophytes (1.19%),
      distal intertarsal and tarsometatarsal joint radiographic changes (9.92%), tarsal
      osteochondrosis lesions (4.40%) and stifle osteochondrosis lesions (0.4%) was
      found. The prevalence of dorsal osteochondral fragments in the
      metacarpophalangeal joint was similar to other studies (1.60%). A higher
      prevalence of vascular channels as well as irregular borders and lucencies was
      evident in the proximal sesamoid bones. There was a higher prevalence of palmar
      metacarpophalangeal and plantar metatarsophalangeal osteochondral fragments (2%
      and 7.10% respectively). Palmar metacarpal disease, metacarpal supracondylar
      lysis, proximal sesamoid bone fractures and carpal osteochondral fragmentation
      were absent in the current study. Additional findings recorded in the current
      study were proximal interphalangeal joint hyperextension (left front 15.13%,
      right front 18.91%), the solar angle (right front 2.38 degrees, left front 2.79
      degrees), the prevalence of carpal bone 1 (30.95%) and carpal bone 5 (1.59%).
      Management, nutrition and genetics in the various groups of Thoroughbred
      yearlings should be further investigated in order to explain the reasons for the
      differences recorded in the current study.

PMID- 22616433
TI  - Brucellae through the food chain: the role of sheep, goats and springbok
      (Antidorcus marsupialis) as sources of human infections in Namibia.
AB  - A confirmed case of human brucellosis motivated an investigation into the
      potential source of infection in Namibia. Since domestic animals are principal
      sources of Brucella infection in humans, 1692 serum samples were screened from
      sheep, goats and cattle from 4 presumably at-risk farms and 900 springbok
      (Antidorcas marsupialis) serum samples from 29 mixed farming units for Brucella
      antibodies by the Rose-Bengal test (RBT) and positive cases confirmed by
      complement fixation test (CFT). To assess the prevalence of human brucellosis,
      137 abattoir employees were tested for Brucella antibodies using the standard
      tube agglutination test (STAT) and by enzyme linked immunosorbent assay (ELISA).
      Cattle and sheep from all 4 farms were negative by RBT and CFT but 2 of the 4
      farms (Ba and C) had 26/42 and 12/285 seropositive goats, respectively. Post
      mortem examination of seropositive goats revealed no gross pathological lesions
      typical of brucellosis except enlarged mesenteric and iliac lymph nodes seen in a
      single buck. Culture for brucellae from organs of seropositive animals was
      negative. None of the wildlife sera tested positive by either RBT or CFT.
      Interviews revealed that besides the case that prompted the investigation, a
      family and another person from other farms with confirmed brucellosis shared a
      common history of consumption of unpasteurised goat milk, home-made goat cheese
      and coffee with raw milk and prior contact with goats, suggesting goats as the
      likely source of infection. All 137 abattoir employees tested negative by STAT,
      but 3 were positive by ELISA. The 3 abattoir workers were clinically normal and
      lacked historical connections with clinical cases. Although goats are often
      associated with B. melitensis, these studies could not explicitly implicate this
      species owing to cross-reactivity with B. abortus, which can also infect goats.
      Nevertheless, these data reinforce the need for a better National Control
      Programme for brucellosis in Namibia.

PMID- 22616435
TI  - Pharmacokinetics of ceftazidime administered to lactating and non-lactating
      goats.
AB  - The aim of this work was to determine the pharmacokinetics of intravenous (i.v.)
      and intramuscular (i.m.) ceftazidime administered to lactating (LTG; n=6) and non
      lactating (NLTG; n=6) healthy Creole goats in 2 trials (T1 and T2). During T1 and
      T2, goats randomly received a single dose of i.m. or i.v. ceftazidime (10 mg/kg).
      Serum concentration of iv ceftazidime in NLTG and LTG goats is best described by
      2 and 3 compartment models, respectively. The pharmacokinetic parameters of iv
      and im ceftazidime administered to LTG and NLTG showed statistically significant
      differences (P < 0.05) in the constants (lamda(z), T1 vs. T2 [i.v.] 0.5 +/- 0.1
      vs. 0.3 +/- 0.1/h; T1 vs. T2 [i.m.] 0.5 +/- 0.2 vs. 0.3 +/- 0.1/h) and in the
      mean times (t(1/2), T1 vs. T2 [i.v.] 1.6 +/- 0.3 vs. 2.3 +/- 0.6 h; T1 vs. T2
      [i.m.] 1.6 +/- 0.7 vs. 2.6 +/- 0.9 h) of elimination. The bioavailability of
      ceftazidime in LTG and NLTG was 113.0 +/- 17.8 and 96.0 +/- 18.0%, respectively.
      Ceftazidime concentration in milk at 2 h was: i.v. = 1.9 +/- 0.2 and i.m. = 2.4
      +/- 0.5 microg/ml; the penetration in milk was i.v. = 18.3 +/- 13.5 and im = 14.3
      +/- 10.6%. Ninety-six hours after i.v. and i.m. administration, residues of the
      drug were not found in milk. In conclusion, ceftazidime, when administered to
      goats, showed high concentration times in serum, good penetration into milk and a
      bioavailability that makes it suitable to be used by the i.m. route.

PMID- 22616434
TI  - A study of some infectious causes of reproductive disorders in cattle owned by
      resource-poor farmers in Gauteng Province, South Africa.
AB  - Two hundred and thirty-nine cattle from Gauteng Province in South Africa were
      tested for various pathogens causing reproductive diseases includingbovine viral
      diarrhoea/mucosal disease (BVD/MD) virus, infectious bovine
      rhinotracheitis/infectious pustular vulvovaginitis (IBR/IPV) virus, Neospora
      caninum and Brucella abortus usingvarious tests. For BVD/MD virus, 49.37% tested
      positive, 74.47% for IBR/IPV virus, 8.96% for Neospora caninum and 3.8% for
      Brucella abortus. The result for Brucella abortus is higher than the national
      average, possibly due to the small sample size. A high seroprevalence of
      antibodies to both BVD/MD virus and IBR/IPV virus was evident. These 2 viruses
      should be considered, in addition to Brucella abortus, when trying to establish
      causes of abortion in cattle. The clinical significance of Neospora caninum as a
      cause of abortion in Gauteng needs further investigation. One hundred and forty
      three bulls were tested for Campylobacter fetus and Trichomonas fetus, and a low
      prevalence of 1.4% and 2.1% respectively was found in this study. The clinical
      implications of these findings are discussed.

PMID- 22616436
TI  - Seroepidemiological survey of Rhodococcus equi infection in asymptomatic horses
      and donkeys from southeast Turkey.
AB  - In order to assess the level of Rhodococcus equi infection in southeast Turkey,
      679 sera from healthy foals and adult horses and 78 sera from donkeys were tested
      by indirect ELISA using a R. equi reference strain (ATCC 33701) as antigen.
      Eighty (11.7%) sera from horses and 9 (11.5%) sera from donkeys with titres >0.85
      were positive. The prevalence of seropositive horses in Sanliurfa Province was
      higher than in Diyarbakir Province; 56 (13.9%) horses in Sanliurfa Province and
      24 (8.7%) horses in Diyarbakir Province were defined as seropositive. In
      Sanliurfa Province 14.5% of female (n=343) and 10.1% of male (n = 59) horses
      tested were defined as seropositive, while in Diyarbakir Province more males
      (11.4%, n=114) were seropositive than females (6.7%, n=163). Horses 1 to 5 years
      of age were found to have the highest seropositivity rate in both provinces. A
      total of 78 sera from donkeys were investigated in Sanliurfa Province, of which 9
      (11.5%) were positive by ELISA. Among the 9 positive sera, 6 (12.8%) were from
      donkeys 1-5 years old and 3 (13.6%) were from donkeys >5 years of age. No
      positive sera were found in donkeys less than 1 year old. Five (12.5%) sera of
      females and 4 (10.5%) sera of males tested were positive. These results indicate
      the existence of R. equi in the horse populations in Sanliurfa and Diyarbakir
      Provinces. Similar infection rates were found for donkeys in Sanliurfa. This
      suggests the importance of serological surveys to diagnose R. equi infection in
      the region and to prevent the zoonotic risk.

PMID- 22616438
TI  - Treatment rationale for dogs poisoned with aldicarb (carbamate pesticide).
AB  - The treatment rationale for dogs poisoned by aldicarb is reviewed from a
      pharmacological perspective. The illegal use of aldicarb to maliciously poison
      dogs is a major problem in some parts of the world. In South Africa, it is
      probably the most common canine poisoning treated by companion animal
      veterinarians. Aldicarb poisoning is an emergency and veterinarians need to be
      able to diagnose it and start with effective treatment immediately to ensure a
      reasonable prognosis. Successful treatment depends on the timely use of an anti
      muscarinic drug (e.g. atropine). Additional supportive treatment options,
      including fluid therapy, diphenhydramine, benzodiazepines and the prevention of
      further absorption (activated charcoal) should also be considered. Possible
      complications after treatment are also briefly discussed.

PMID- 22616437
TI  - A literature review and investigation of staphylococcal necrotic dermatitis in
      sheep.
AB  - An outbreak of necrotic dermatitis in sheep was intensively investigated.
      Initially 19 of 147 Letelle (Merino-type) ewes were identified but closer
      inspection revealed 57 sheep that had skin lesions, some very slight, and that
      the majority (46 or 80%) had lesions only above the lips. A small number of them
      had multiple lesions on the legs or vulvae apart from lip lesions. Seven had only
      vulvar lesions and 2 only leg lesions. Among the sheep with lip lesions, twice as
      many had lesions on the right as on the left. Electron micrographs did not reveal
      any virus particles from the lesions, but all bacterial swabs yielded pure
      cultures of beta-haemolytic, Gram-positive cocci that were catalase, coagulase
      and DNase positive. The organism was identified as Staphylococcus aureus.
      Histopathology was consistent with a dermotoxic insult. A review of available
      literature indicated that this outbreak was consistent with a diagnosis of ovine
      necrotic (staphylococcal) dermatitis, supported by data on signalment, lesions,
      distribution, size, number, epidemiology as well as specific tests. The range of
      differential diagnoses and possible confusers are discussed.

PMID- 22616439
TI  - Patent ductus arteriosus repair in general practice.
AB  - A 3-month-old female German Shepherd puppy was presented for routine vaccination.
      Clinical evaluation revealed a grade 5/6 continuous murmur with the point of
      maximal intensity over the left 4th intercostal space. Echocardiography revealed
      a patent ductus arteriosus (PDA). The PDA was closed by a team of general
      practitioners using the Jackson-Henderson technique, via a standard 4th
      intercostal thoracotomy. A multi-modal approach to analgesia and premedication
      was employed. A successful outcome was achieved with no murmur or evidence of
      cardiac disease present 6 months after surgical occlusion. The literature is
      reviewed with an emphasis placed on choosing techniques that are appropriate to
      the level of expertise of the surgical and anaesthetic teams, as well as the
      surgical facilities available.

PMID- 22616440
TI  - Hypercalcaemia in a dog with primary hypothyroidism.
AB  - A 7-year-old female beagle was evaluated for symptomatic hypercalcaemia and
      primary hypothyroidism. Clinical findings were typical for hypothyroidism. Plasma
      parathyroid hormone was low and obvious causes for the hypercalcaemia were ruled
      out by means of abdominal ultrasonography, ultrasonography of the parathyroid
      glands, survey thoracic radiographs, and fine needle aspirate cytology of the
      spleen, liver, and peripheral lymph nodes. Treatment with thyroxine resulted in
      resolution of the hypercalcaemia after approximately 9 weeks of therapy. This is
      the 1st report of primary adult-onset hypothyroidism associated with symptomatic
      hypercalcaemia in a dog.

PMID- 22616441
TI  - Barbiturate ingestion in three adult captive tigers (Panthera tigris) and
      concomitant fatal botulism of one.
AB  - Zoo animals, including tigers, have been reported to suffer from barbiturate
      intoxication, with pentabarbitone being most commonly recorded. Clinical signs
      range from mild ataxia to general anaesthesia with recovery over hours to days
      with several factors affecting hepatic barbiturate metabolism and tissue
      partitioning. Botulism is an often fatal intoxication in man, animals, birds and
      certain fish. The occurrence in carnivores is uncommon to rare, with only 2
      reports found of botulism in felids. This report relates to 3 adult captive
      cohabiting tigers that simultaneously developed signs of abdominal discomfort,
      progressive ataxia, recumbency and comatose sleep resembling stage 2 anaesthesia,
      alternating with periods of distracted wakefulness and ataxic movements. These
      signs occurred 4 days after being fed the carcass of a horse that had ostensibly
      died of colic and not been euthanased. The male tiger that was the dominant
      animal in the feeding hierarchy was worst affected and had to be given
      intravenous fluids. The female that was lowest in hierarchy was unaffected. After
      48-72 hours of treatment at the Onderstepoort Veterinary Academic Hospital the
      females could eat and made an uneventful recovery. The male tiger showed partial
      recovery but died during the night a few hours after drinking water on his return
      to the owner. Necropsy revealed severe oesophageal dilation and impaction with
      decaying grass; some of this material and water were present in the pharynx and
      trachea, and had been aspirated causing acute widespread bronchopneumonia. Colon
      content tested negative for common pesticides but, together with liver, tested
      positive for barbiturate. Serum taken on the day of admission had tested negative
      for barbiturate and the residual serum from the 3 animals later tested negative
      for botulinum toxin. Colon and oesophageal content from the male at necropsy were
      positive for Clostridium botulinum toxin type C by the mouse bioassay
      neutralisation test, confirming that this male had had concomitant barbiturate
      toxicity and botulism, and had succumbed to aspiration bronchopneumonia secondary
      to pharyngeal, laryngeal and oesophageal paralysis and oesophageal

PMID- 22616442
TI  - A case study of rabies diagnosis from formalin-fixed brain material.
AB  - Rabies is caused by several Lyssavirus species, a group of negative sense RNA
      viruses. Although rabies is preventable, it is often neglected particularly in
      developing countries in the face of many competing public and veterinary health
      priorities. Epidemiological information based on laboratory-based surveillance
      data is critical to adequately strategise control and prevention plans. In this
      regard the fluorescent antibody test for rabies virus antigen in brain tissues is
      still considered the basic requirement for laboratory confirmation of animal
      cases. Occasionally brain tissues from suspected rabid animals are still
      submitted in formalin, although this has been discouraged for a number of years.
      Immunohistochemical testing or a modified fluorescent antibody technique can be
      performed on such samples. However, this method is cumbersome and cannot
      distinguish between different Lyssavirus species. Owing to RNA degradation in
      formalin-fixed tissues, conventional RT-PCR methodologies have also been proven
      to be unreliable. This report is concerned with a rabies case in a domestic dog
      from an area in South Africa where rabies is not common. Typing of the virus
      involved was therefore important, but the only available sample was submitted as
      a formalin-fixed specimen. A real-time RT-PCR method was therefore applied and it
      was possible to confirm rabies and obtain phylogenetic information that indicated
      a close relationship between this virus and the canid rabies virus variants from
      another province (KwaZulu-Natal) in South Africa.

PMID- 22616443
TI  - 2011 nutritional assessment guidelines.
AB  - Careful assessment of nutritional needs of dogs and cats must be taken into
      consideration in order to maintain optimum health, be part of a treatment regimen
      for a diseased state, or to maximise the quality of life in all animals.
      Therefore, the goal of these WSAVA Guidelines is that a nutritional assessment
      and specific nutritional recommendation be made on every patient on every visit.
      This will become known as the 5th Vital Assessment (5VA), following the four
      vital assessments of temperature, pulse, respiration and pain that are already
      addressed on each patient interaction. Routinely doing a brief screening
      evaluation of the nutritional status during history taking and the physical
      examination can be seamlessly performed as part of every patient exam. Nutrition
      related risk factors that can be easily identified from the history and physical
      examination include age (growing or old), suboptimal body condition score
      (overweight or thin), muscle loss, atypical or homemade diet, medical conditions,
      or changes in appetite. An extended evaluation would follow, if one or more risk
      factors is identified on screening. These guidelines provide criteria to evaluate
      the animal and the diet, as well as key feeding and environmental factors. In
      addition, recommendations for interpretation, analysis, and action are included
      so that a plan for optimising the animal's nutritional status can be instituted.
      Client compliance with nutritional recommendations requires input from the
      veterinarian, veterinary technicians/nurses, and the hospital staff. A team
      approach to continuous nutritional education, implementation of appropriate
      protocols, and focused client communication, utilising these WSAVA Nutritional
      Guidelines, are key components to reach this 5VA goal.

PMID- 22616444
TI  - Assessing readiness to change of a high fall risk patient: a case report.
AB  - The case report discusses a patient with an extensive history offalls living in
      the community. The patient's medical record was analyzed and an informal
      interview was conducted with the patient to provide an overview of his care
      provided by the Veterans Health Administration (VHA) Home-Based Primary Care
      (HBPC) program from June 2008 to February 2011. The report will also apply the
      transtheoretical model of behavioral change to discuss the behavior change
      process of a high fall risk patient. Applying this model to the high fall risk
      population may assist with decreasing the frustration of clinicians and
      caregivers, as it acknowledges the "smaller gains" with fall prevention.

PMID- 22616445
TI  - Death, drugs, and disaster: mortality among New Orleans' homeless.
AB  - Tracking homeless individuals over time has proved to be extremely difficult;
      thus, only limited longitudinal data on the homeless exist. We analyze
      longitudinal data originally collected from the New Orleans Homeless Substance
      Abusers Program in 1991-1993, supplemented with mortality data for the same
      sample by year 2010. We use social bonding theory to examine the effect of
      conventional social ties on mortality among a sample of substance abusing
      homeless people. This is of special concern when researching the older homeless
      persons. We find that social bonding theory does not help to understand mortality
      among this population. However, alcohol abuse, as compared to crack cocaine, does
      increase the likelihood of early mortality.

PMID- 22616446
TI  - Eleven blogs on aging.

PMID- 22616447
TI  - Recertification in New York State: the revolving door of the Medicare savings
      program.

PMID- 22616448
TI  - Aging, widowhood, multiple sclerosis, and a dog. Interview by Marian Brickner.

PMID- 22616451
TI  - Transforming power of nature.

PMID- 22616450
TI  - Raising your voice to transform health care.

PMID- 22616449
TI  - The next generation of senior services: responding to health reform.

PMID- 22616452
TI  - Ritual in the ecosystem of caregiving.

PMID- 22616453
TI  - The people to People Ambassador Program: a catalyst for change.

PMID- 22616454
TI  - Conscious change: a Zen perspective.

PMID- 22616455
TI  - [The professional report, a tool at the heart of care].

PMID- 22616458
TI  - [Information and communication technologies in pediatrics, ethical reflection].
AB  - Information and communication technologies play an important role in the field of
      paediatrics. These aids diversify and supplement information and medical
      monitoring, and call also transform the helping relationship between the nurse
      and the child. Some areas of reflection enable these technologies to be
      approached from an ethical angle.

PMID- 22616457
TI  - [Information technology].

PMID- 22616456
TI  - [Care of the umbilical cord in developing countries].

PMID- 22616459
TI  - [The Serious Game, a care tool for hospitalized children].
AB  - For the last 4 years, the paediatric department of Seclin hospital in the north
      of France has provided children and professionals with a fun tool which helps to
      inform young children and assess their pain, Dolo:kids. This Serious Game also
      helps to make the hospital environment less traumatic for the patient.

PMID- 22616460
TI  - [Baby online to support the mother-baby relationship in neonatalogy].
AB  - Neonatal separations are always harmful to the development of the parent/baby
      relationship. At Ales general hospital, the Bebe online scheme enables live
      images to be transmitted remotely and safely between maternity wards and
      neonatalogy, physically distant from each other. Supervised by the nursing team,
      it supports the attachment process by giving parents the possibility of
      maintainingvisual contact with their newborn.

PMID- 22616461
TI  - [Information and pediatric advice by telephone].
AB  - Pediatrie Info is a call center which enables parents to speak to doctors trained
      in paediatric issues 24 hours a day, 7 days a week. Marketed initially to
      companies and organisations, this service meets a real need in terms of
      paediatric advice and enables the influx of patients to emergency departments to
      be controlled upstream.

PMID- 22616462
TI  - [The digital avatar, an assistant in adolescent psychiatry].
AB  - The digital universe, from the internet to video games, arouses mixed feelings in
      parents of adolescents. However, it is possible to use the growing "digitisation"
      of the relationships between young people to develop care tools. Avatars or
      virtual characters, for example, make it possible to develop a relationship with
      adolescents hospitalised in child psychiatry units.

PMID- 22616463
TI  - [Protecting children and adolescents from the risks and excesses of the
      internet].

PMID- 22616464
TI  - [Bibliography. Information technology].

PMID- 22616465
TI  - [Enabling parents to feel useful in the care of their preterm baby].
AB  - In a department such as neonatal intensive care, where techniques are constantly
      evolving, the relational aspect of support for the parents given by the neonatal
      nurse can often take a back seat to the technical care. However, this support is
      necessary for the psychological well-being of the families. Indeed, in order to
      access parenthood, parents need to feel useful and to be involved in the care of
      their preterm baby.

PMID- 22616466
TI  - [The role of the nurse in the health centre of the Maison de Solenn].
AB  - Adolescent units provide anonymous and free consultations with different health
      professionals. At the Maison de Solenn in Paris, the initial nurse consultation
      enables particular attention to be paid to the adolescent in a special health
      centre. The nurse is responsible for assessing the situation and orienting the
      adolescents to meet their specific needs.

PMID- 22616467
TI  - [Entering into a relationship with an infant].
AB  - Many infants suffer from having to adapt to an environment which does not appeal
      to them. As the guarantor of a safe environment, the adult enters into a
      relationship with the infant considered as a real person in his or her own right.
      From this authentic encounter support for infants in their discovery of their
      surroundings can be developed.

PMID- 22616468
TI  - Effective doctor-patient communication--a hit or a myth?

PMID- 22616469
TI  - Treffert's work with 'extraordinary people' reaches global community.

PMID- 22616470
TI  - A potpourri.

PMID- 22616471
TI  - Prevalence of involuntary commitment for alcohol dependence.
AB  - BACKGROUND: Alcohol dependence is a chronic relapsing illness. While some
      patients respond to treatment, others continue to drink alcohol and suffer
      serious health effects such as delirium tremens, liver failure, heart disease,
      and central nervous effects. One option society has used to force treatment and
      abstinence is the legal mechanism of "involuntary commitment." The goal of this
      study was to determine the utilization of "involuntary commitment" among the 72
      counties in Wisconsin. METHODS: A statewide survey was conducted using a mailed
      survey to assess the current use of this treatment option. RESULTS: Forty-nine
      counties responded to the survey (68%); the mean number of commitments in the
      last year was 5 with a range of 0 to 30. Of the petitioners who participated in
      the commitment, 98% were family members, 62% were friends, 49% were physicians,
      and 26% were counselors. Over half of the respondents (53%) felt that the process
      was effective in helping people deal with their alcoholism. DISCUSSION: The
      overall perception among those surveyed is that involuntary commitment for the
      treatment of alcohol dependence can help addicted persons, but its utilization
      varies by county in Wisconsin. Physicians may consider exploring the use of this
      legal process to assist patients struggling with alcoholism.

PMID- 22616472
TI  - A case of pulmonary embolism and stroke in a 16-year-old girl.
AB  - A 16-year-old girl arrived intubated to the emergency department. She had
      shortness of breath and cough for 2 days with leg pain. On arrival, she was
      hemodynamically stable with an unremarkable physical exam. Electrocardiogram
      revealed a prolonged QT interval; laboratory work-up was normal except for an
      elevated dimerized plasmin fragment D. Acute pulmonary embolism was confirmed by
      a chest computed tomography scan. A lower extremity duplex scan was negative and
      echocardiogram revealed a patent foramen ovale with bidirectional shunting. An
      inferior vena cava filter was placed to prevent acute recurrence and
      unfractionated heparin was initiated. The next day she was noted to have right
      hemiparesis. Stroke was confirmed by magnetic resonance imaging. The patient
      underwent mechanical clot retrieval and was discharged on anticoagulation therapy
      to a brain rehabilitation unit.

PMID- 22616473
TI  - Pulmonary lymphomatoid granulomatosis presenting with neuropathy and renal
      nodules.
AB  - Pulmonary lymphomatoid granulomatosis is a rare diagnosis that frequently
      presents with a constellation of seemingly unrelated signs and symptoms. It can
      present with bilateral pulmonary nodules, subcutaneous skin nodules, renal
      nodules, and peripheral neuropathy. Its protean manifestation, both clinically
      and radiologically, may delay a definitive diagnosis. We present the case of a
      patient who had thoracotomy twice and waited for nearly a year to get the final
      diagnosis because of the presence of a variety of seemingly unrelated symptoms.

PMID- 22616474
TI  - An acute, progressive encephalopathy.
AB  - Rabies holds the distinction of having the highest case-fatality ratio of any
      infectious disease. Aggressive public health campaigns have reduced the incidence
      of this disease in the United States to a record low. We report a case of this
      increasingly rare disease in a 70-year-old man in Wisconsin.

PMID- 22616475
TI  - Influenza vaccination as a condition of employment for a large regional health
      care system.
AB  - Aurora Health Care (Aurora) is a large integrated delivery system in eastern
      Wisconsin/northern Illinois that serves over 1.2 million patients per year and
      has over 30,000 employees. Aurora adopted a policy of annual influenza
      vaccination as a condition of employment for all employees during May 2011, to
      commence with the 2011-2012 influenza season. The percentage of employees
      vaccinated against influenza had been below 100%-the rate recommended by the
      Centers for Disease Control and Prevention. The intervention increased the
      percentage of employees vaccinated to 97.7% in the first year of implementation,
      compared to 71% in 2010 (P < 0.00001). No medical or economic reactions to this
      intervention were determined to be unmanageable. Aurora recommends that health
      systems that currently fail to achieve 90% employee influenza vaccination rates
      adopt a similar process.

PMID- 22616476
TI  - Advance care planning conversations can be difficult, but essential.

PMID- 22616477
TI  - Transforming the research environment and culture for the betterment of health in
      Wisconsin.

PMID- 22616478
TI  - Expression of complete metabolic pathways in transgenic plants.
AB  - Plant genetic engineering emerged as a methodology to introduce only few
      transgenes into the plant genome. Following fast-paced developments of the past
      few decades, engineering of much larger numbers of transgenes became a reality,
      allowing to introduce full metabolic pathways from other organisms into plants
      and generate transgenics with startling new traits. From the advent of the
      classical plant genetic engineering, the transgenes were introduced into the
      nuclear genome of the plant cell, and this strategy still is quite successful
      when applied to few transgenes. However, for introducing large number of
      transgenes, we advocate that the chloroplast genome is a superior choice,
      especially for engineering of new complete metabolic pathways into plants. The
      ability to genetically engineer plants with complex and fully functional
      metabolic pathways from other organisms bears a substantial promise in generation
      of pharmaceuticals, i.e., biopharming, and new agricultural crops with that
      traits never existed before, leading to enhancement in quality of human life.

PMID- 22616479
TI  - Assessing compositional variability through graphical analysis and Bayesian
      statistical approaches: case studies on transgenic crops.
AB  - New transgenic (GM) crops are subjected to extensive safety assessments that
      include compositional comparisons with conventional counterparts as a cornerstone
      of the process. The influence of germplasm, location, environment, and agronomic
      treatments on compositional variability is, however, often obscured in these pair
      wise comparisons. Furthermore, classical statistical significance testing can
      often provide an incomplete and over-simplified summary of highly responsive
      variables such as crop composition. In order to more clearly describe the
      influence of the numerous sources of compositional variation we present an
      introduction to two alternative but complementary approaches to data analysis and
      interpretation. These include i) exploratory data analysis (EDA) with its
      emphasis on visualization and graphics-based approaches and ii) Bayesian
      statistical methodology that provides easily interpretable and meaningful
      evaluations of data in terms of probability distributions. The EDA case-studies
      include analyses of herbicide-tolerant GM soybean and insect-protected GM maize
      and soybean. Bayesian approaches are presented in an analysis of herbicide
      tolerant GM soybean. Advantages of these approaches over classical frequentist
      significance testing include the more direct interpretation of results in terms
      of probabilities pertaining to quantities of interest and no confusion over the
      application of corrections for multiple comparisons. It is concluded that a
      standardized framework for these methodologies could provide specific advantages
      through enhanced clarity of presentation and interpretation in comparative
      assessments of crop composition.

PMID- 22616480
TI  - Application and use of Inulin as a tool for therapeutic drug delivery.
AB  - Inulin is a polysaccharide with an extensive range of therapeutic uses such as a
      vehicle in drug delivery vehicle, as a diagnostic/analytical tool or as a dietary
      fibre with additional health benefits. In the main, much research has focussed on
      inulin as a drug delivery carrier for colon-targeted drug delivery. The
      justification for this is its potential to survive the stomach's acidic
      environment. This unique stability and strength is utilized in many ways to
      deliver drugs safely to colon, where they can be easily absorbed through the gut
      epithelium into the blood. Inulin based hydrodynamic research will be useful to
      discover the potential of inulin.

PMID- 22616481
TI  - Plant natural products: history, limitations and the potential of cambial
      meristematic cells.
AB  - Humans have utilised plant derived natural products as medicines for millenia.
      Moreover, many contemporary pharmaceuticals are also natural products or
      derivatives thereof. However, the full potential of these compounds remains to be
      exploited because often they are: complex and difficult to synthesise; found in
      low quantities; produced by undomesticated and sometimes rare plants; and, their
      synthesis is routinely influenced by weather conditions. Potentially, the in
      vitro culture of cells from the corresponding plant species could circumvent some
      of these problems but the growth of plant cells on an industrial scale is also
      problematic. The recent isolation and culture of cambial meristematic cells
      (CMCs), stem cells which ordinarily generate the plant vasculature, may now
      provide a key platform technology to help realise the full potential of plant
      natural products.

PMID- 22616482
TI  - Ras and Rho small G proteins: insights from the Schizophyllum commune genome
      sequence and comparisons to other fungi.
AB  - Unlike in animal cells and yeasts, the Ras and Rho small G proteins and their
      regulators have not received extensive research attention in the case of the
      filamentous fungi. In an effort to begin to rectify this deficiency, the genome
      sequence of the basidiomycete mushroom Schizophyllum commune was searched for all
      known components of the Ras and Rho signalling pathways. The results of this
      study should provide an impetus for further detailed investigations into their
      role in polarized hyphal growth, sexual reproduction and fruiting body
      development. These processes have long been the targets for genetic and cell
      biological research in this fungus.

PMID- 22616484
TI  - The interaction of dietary fibres with disulphide bonds (S-S) and a potential
      strategy to reduce the toxicity of the gluten proteins in coeliac disease.

PMID- 22616483
TI  - The potential benefit of non-purified islets preparations for islet
      transplantation.
AB  - Since the advent of islet transplantation, there has been a significant emphasis
      on the importance of islet purity despite an inevitable associated loss of islet
      mass during the purification process. One of the key elements of the 'Edmonton
      Protocol' for islet transplantation published in 2000 was an emphasis on the need
      for sequential transplants of highly purified islets (averaging 24% beta cell
      purity) and the close correlation between the numbers of islets transplanted and
      the success of the procedure. However, the emphasis on islet purity may warrant
      further consideration as auto transplantation of non-purified islets currently
      provides the most successful insulin independence rates within the field of islet
      transplantation. While the role of auto and allo immunity could contribute to the
      differences in the success rates it is clear that within the clinical setting,
      significant acinar and ductal contamination is well tolerated. However, one could
      go further and hypothesize that extra-insular tissue including acinar tissue,
      ductal tissue, peri-pancreatic lymph nodes and vascular tissue actually confer an
      advantage to islet survival/function and may even contribute to the insulin
      secreting capacity of the graft post transplant. As such this review will assess
      the influence of extra-insular pancreatic tissue on the results of islet
      transplantation based on published evidence and will also explore the possibility
      that non-islet pancreatic cells are capable of differentiating into a beta cell
      phenotype in vivo contributing to an ongoing regeneration of endocrine mass
      during the period following transplantation.

PMID- 22616485
TI  - Arrayed protein library technology for therapeutic biologic discovery.

PMID- 22616486
TI  - Production platforms for biotherapeutic glycoproteins. Occurrence, impact, and
      challenges of non-human sialylation.
AB  - One of the fastest growing fields in the pharmaceutical industry is the market
      for therapeutic glycoproteins. Today, these molecules play a major role in the
      treatment of various diseases, and include several protein classes, i.e.,
      clotting factors, hormones, cytokines, antisera, enzymes, enzyme inhibitors, Ig
      Fc-Fusion proteins, and monoclonal antibodies. Optimal glycosylation is critical
      for therapeutic glycoproteins, as glycans can influence their yield,
      immunogenicity and efficacy, which impact the costs and success of such
      treatments. While several mammalian cell expression systems currently used can
      produce therapeutic glycoproteins that are mostly decorated with human-like
      glycans, they can differ from human glycans by presenting two structures at the
      terminal and therefore most exposed position. First, natural human N-glycans are
      lacking the terminal Gal 1-3Gal (alpha-Gal) modification; and second, they do not
      contain the non-human sialic acid N-glycolylneuraminic acid (Neu5Gc). All humans
      spontaneously express antibodies against both of these glycan structures, risking
      increased immunogenicity of biotherapeutics carrying such non-human glycan
      epitopes. However, in striking contrast to the alpha-Gal epitope, exogenous
      Neu5Gc can be metabolically incorporated into human cells and presented on
      expressed glycoproteins in several possible epitopes. Recent work has
      demonstrated that this non-human sialic acid is found in widely varying amounts
      on biotherapeutic glycoproteins approved for treatment of various medical
      conditions. Neu5Gc on glycans of these medical agents likely originates from the
      production process involving the non-human mammalian cell lines and/or the
      addition of animal-derived tissue culture supplements. Further studies are needed
      to fully understand the impact of Neu5Gc in biotherapeutic agents. Similar
      concerns apply to human cells prepared for allo- or auto-transplantation, that
      have been grown in animal-derived tissue culture supplements.

PMID- 22616487
TI  - Meeting report: the stability and degradation of complex carbohydrate structures:
      mechanisms and measurement.

PMID- 22616488
TI  - [Multiple-branched polyp in screening colonoscopy].

PMID- 22616489
TI  - Colonic distension and constipation.

PMID- 22616490
TI  - [World Gastroenterology Organisation: origin and future on its 50th foundation
      anniversary].

PMID- 22616491
TI  - [Julio Vicente Uriburu].

PMID- 22616492
TI  - [Quality of life in children and adolescents with celiac disease: Argentinian
      version of the specific questionnaire CDDUX].
AB  - The treatment of the celiac disease implies lifelong alimentary restrictions,
      with impact on social and family activities. Therefore, it is important to
      consider the health-related quality of life (HRQL) in the approach. OBJECTIVE: To
      validate the Argentinian version of the specific tool CDDUX in order to measure
      HRQL in children and adolescents with celiac disease. METHODS: In this
      prospective and transversal investigation, children and adolescents from 8 to 18
      years-old who attended the "Prof Dr. J P Garrahan" Hospital and their father or
      tutor were recruited, between June 2009 and May 2010. Participants were given the
      informed consent sheet, the Argentinian version of CDDUX, a visual analogue scale
      (VAS) and the PedsQL 4.0, generic questionnaire. Sociodemographic data were also
      registered. RESULTS: We included 193 patients, female 56.5%, with these age
      categories: 8 to 11 years-old 48.7%, 12 to 15 years-old 43%, 16 to 18 years-old
      8.3%. Schooling was below the standard level in children in 23.4% of cases,
      primary school incomplete in adults in 11.4%. Socioeconomic status was poor in
      24.4% of cases and indigent in 4.7%. Unsatisfied basic needs were observed in
      41.5% of patients. The feasibility was: average filling time: 4 minutes in
      children and parents. All completed the questionnaire. Without help: 91.7% in
      children and 79.8% in parents. The reliability was: Cronbach alpha's internal
      consistency 0.84 in children and 0.88 in parents. The construction validity was:
      moderate correlation between CDDUX and PedsQL (P < 0.001), low between parents
      and children in CDDUX (P < 0.001), moderate and negative between CDDUX and VAS (P
      < 0.001). Scores of CDDUX were lower in poor people and significant for parents
      (P = 0.04). Higher scores of CDDUX were observed in those patients who complied
      with the gluten-free diet (P < 0001). Conclusion. The Argentinian version of
      CDDUX was both feasible and easy to administer in the studied population. It
      shows good psychometric properties in children and parents.

PMID- 22616493
TI  - IGF-1 levels in different stages of liver steatosis and its association with
      metabolic syndrome.
AB  - BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is the hepatic
      manifestation of the metabolic syndrome related to insulin resistance. Insulin
      like growth factor 1 (IGF-1) is mainly produced by hepatocytes and its secretion
      is stimulated by growth hormone. Our aim was to assess possible changes in IGF-1
      levels in patients with different ultrasonography stages of NAFLD and its
      association with hyperlipidemia, impaired glucose tolerance, non-insulin
      dependant type 2 diabetes, waist circumference, obesity and arterial
      hypertension. METHODS: One hundred and ten consecutive patients were evaluated.
      RESULTS: IGF-1 levels decreased as liver steatosis worsened. There was a
      statistically significant difference between mild-moderate steatosis on one hand,
      and severe steatosis on the other (142 vs. 110, P < 0.05). Homeostasis model
      assessment of insulin resistance (HOMA) and insulin levels showed a tendency to
      inverse association with IGF-1, but it was not statistically significant. HOMA
      significantly increased in severe liver steatosis when compared with mild
      moderate steatosis (6.20 vs. 3.99, P < 0.05). Insulin levels also showed a
      significant increase (3.01 +/- 0.61 vs. 2.59 +/- 0.56, P < 0.05). Body mass index
      showed a significant inverse correlation with IGF-1 level (r = -0.19, P < 0.05)
      and a tendency to increase as liver steatosis worsened. Waist circumference
      increased significantly as liver steatosis worsened (severe vs. mild-moderate:
      114 vs. 100, P < 0.05). CONCLUSIONS: IGF-1 levels showed a decrease as liver
      steatosis worsened. This difference was statistically significant between mild
      moderate and severe stetaosis. Inverse correlation between IGF-1 levels and BMI
      was also statistically significant. There was no statistically significant
      correlation between IGF-1 levels and HOMA and insulin levels.

PMID- 22616494
TI  - [N-butyl-2-cyanoacrylate for the treatment of gastric varices].
AB  - OBJECTIVE: To evaluate the success of the treatment with cyanoacrylate in primary
      hemostasis, rebleeding, and gastric varices eradication. MATERIAL AND METHODS: In
      this retrospective study 65 patients with gastric varices treated with N-butyl-2
      cyanoacrylate (Histoacryl) were included from January 1999 to January 2008. We
      used a solution of 0,5 mL of cyanoacrylate and 0.9 mL of lipiodol, utilizing an
      average of 3.46 mL of this mixture per session (range 1 to 6 mL). Sclerosing
      needles of 21 gauge were used. Patients were sedated. Data were analyzed using a
      chi-squared test. RESULTS: Sixty-five patients were included, 42 men and 23 women
      with an average age of 53.8 years (range 18 to 76 years). The etiology of the
      portal hypertension (PH) was cirrhosis in 52 patients (80%), prehepatic PH in 7
      (10.8%), and segmentary PH in 3 (4.6%), and non-classified in 3 (4.6%). Cirrhotic
      patients were classified as Child A in 21 cases, Child B in 25 and Child C in 6.
      According to the Sarin classification, 7 patients had gastric-oesophageal varices
      (GOV) type 1, 32 GOV2, 8 GOV1 and 2, and 8 isolated gastric varices (IGV) type 1.
      Fifty-six patients (86%) presented active bleeding or stigmata of recent bleeding
      at time of initial endoscopy. Primary hemostasis was achieved in 50 of them (89%)
      and the remaining 6 required a second session. Eleven patients presented
      rebleeding within the following 6 weeks and were again treated with
      cyanoacrylate. Hemostasis was achieved in 8 of them, 2 were referred for surgical
      management, and 1 received endovascular treatment. Follow-up was able in 53
      patients for an average period of 11 months (range 1 to 81 months). During this
      period, 7 patients presented an episode ofrebleeding and were treated with
      cyanoacrylate, achieving hemostasis. Eradication of varices was documented on 21
      patients (39.6%). The global rate of rebleeding was 37%. One patient developed
      splenic vein thrombosis as a major complication of treatment. CONCLUSION:
      Definitive hemostasis was achieved in 94.6% of patients, with primary hemostasis
      in 89%. The global rate of rebleeding was 37% and the rate of major complications
      associated with treatment 0.6%. Eradication of gastric varices was achieved in
      35.8% of cases. As these data show, it can be concluded that butyl-cyanoacrylate
      constitutes an effective method for the treatment of gastric variceal bleeding.

PMID- 22616495
TI  - [Adherence of physicians to colorectal cancer screening: which is their
      compliance to this strategy?].
AB  - BACKGROUND: Colorectal cancer (CRC) screening is strongly recommended as early
      diagnosis improves survival and reduces mortality. However, the adherence in
      general population is about 50% and even lower among physicians. OBJECTIVE: 1) To
      estimate the percentage of physicians that had done a screening test. 2) To
      estimate the frequency of tests used by these professionals. METHODS: We
      conducted an anonymous survey among 269 physicians, 50-year-old or more, from
      four hospitals and four scientific conventions in 2008. This validated survey
      included specialty, family history, compliance to screening, clinical features at
      screening, age, tests used reasons for having or not done the tests and results.
      RESULTS: Twenty-four hundred and two data surveys were included (response rate
      90%). Average age was 58+6 years. Specialties were Internal Medicine (72%),
      Surgery (18%) and others (9%). One hundred physicians had a test done [41% (IC95%
      35-47)]. The most used test was colonoscopy [70% (IC 95% 60-78)], followed by
      barium enema [10% (IC 95% 5-18)]. From screened physicians, 36% had family
      history of CRC, 63% did not and 1% was unaware of this antecedent. Physicians
      referred the following reasons for not being compliant: personal decision, fear
      of the procedure, insufficient knowledge of guidelines and lack of time.
      CONCLUSIONS: The compliance of physicians to CRC screening is suboptimal. New
      strategies should be implemented to achieve changes in health habits of
      physicians and compliance to preventive strategies.

PMID- 22616496
TI  - [Frequency of imperforate anus and associated risk factors in patients with Down
      syndrome].
AB  - OBJECTIVES: To establish the frequency of imperforate anus (IA) in the population
      with Down syndrome (DS) and study the associated risk factors. METHODS: An
      observational clinical study case control type was performed. The patients were
      evaluated at the Unit of Medical Genetics, University of the Andes, from February
      2006 to February 2011. The patients with DS and IA were compared with 20 DS
      without IA. Antecedents of parents were obtained. RESULTS: The frequency de IA in
      the population with DS was 4.79%. The presence of fever in the first trimester of
      gestation and the rural origin were associated as risk factors of AI in patients
      with DS [OR: 25.33 (IC 95% 2.07- 310.76; P = 0.009) and OR: 7.50 (IC 95% 1.09 -
      51.52; P = 0.043), respectively]. The maternal age superior to 35 years presented
      a marginal significance (P = 0.048). CONCLUSIONS: These papers emphasize the high
      frequency of IA in patients with DS and recommend to investigate the prenatal and
      environmental risk factors that can increase the presence of this anorectal
      anomaly in the population with DS, in order to consider them in the programs of
      prevention of congenital pathologies.

PMID- 22616497
TI  - [Esopheal foreign body impaction].
AB  - Esophageal ingestion of foreign bodies is a frequent urgency. It occurs more
      commonly in patients with psychiatric disorders, prisoners and extreme ages of
      the life. Early upper endoscopy is the method of choice for the treatment of
      symptomatic patients. Surgery is only considered when a complication is present
      or the extraction can not be done by the endoscopist. We report a case of a 34
      year-old male who voluntarily ingested an uncommon foreign body. Surgical
      treatment was required because of impaction after endoscopic maneuvers and
      suspicion of esophageal perforation.

PMID- 22616498
TI  - [Jejuno-jejunal intussusception as presentation of a primary lung carcinoma: a
      case report].
AB  - Intestinal metastases from lung cancer are exceptional and even more rare is
      their manifestation before the primary tumor. The clinical manifestation may
      require surgical resection because of intestinal perforation, hemorrhage,
      intestinal obstruction or partial blockage as in the case that we report.
      Survival in the few cases reported, is low and generally does not exceed 20
      weeks, regardless of the treatment performed. We report the case of a jejuno
      jejunal intussusception manifested by occlusive syndrome and gastrointestinal
      bleeding due to the metastasis of an adenosquamous lung carcinoma.

PMID- 22616499
TI  - [Digestive bleeding and acute abdomen caused by jejunal diverticulosis. Case
      report].
AB  - We present a patient with acute abdomen and digestive bleeding caused by jejunal
      diverticulosis. Jejunal diverticulosis, mainly asymptomatic, when is symptomatic
      have a wide clinical spectrum, ranging from chronic anemic syndrome to acute
      abdomen. In this communication, we reviewed the clinical presentation, the
      pathogenesis and the treatment this infrequent pathology.

PMID- 22616500
TI  - [Acute renal failure and chronic diarrhea: McKittrick-Wheelock syndrome].
AB  - In 1954, McKittrick and Wheelock described for the first time a syndrome
      presenting chronic lost of fluid and electrolytes secondary to chronic diarrhea,
      associated to large rectal villous adenomas. We report a case of a 75-year-old
      female who presented chronic diarrhea (3 to 4 depositions per day in the last
      year), accompanied by acute renal failure. In the rectal tact, we objective the
      presence of a mass of soft consistency with an irregular surface, occupying
      approximately two thirds of the circumference, at about 3 cm from the anal
      margin. It was confirmed by the colonoscopy and the patology was informed as
      villous adenoma, producing chronic diarrhea or McKittrick-Wheelock syndrome. We
      decide the surgical approach after the normalization of patient's general status
      and a proctectomy with coloanal anastomosis was performed. We conclude that we
      must think about this syndrome in aged patients with chronic diarrhea,
      alterations of the electrolyte balance and presence of renal failure. Surgery
      treatment after the replacement of water and electrolytes is the unique curative
      treatment. The absence of this can cause the death of these patients.

PMID- 22616501
TI  - [Hepatogastric fistula after chemoembolization of liver metastasis: a case
      report].
AB  - Liver metastases of colorectal cancer are a challenge in current oncology. Less
      than 5% of untreated patients are alive after 5 years of diagnosis. The only
      curative treatment is surgical resection, but there are other options for
      palliative or neoadjuvant treatment such as transarterial chemoembolization.
      Serious complications after liver chemoembolization are very rare, and one of the
      possible complications is a liver abscess. We report a case of hepatogastric
      fistula caused by a liver abscess ten days after the chemoembolization of a liver
      metastasis. It was treated surgically with left hepatectomy and parcial
      gastrectomy, with good outcome. There are only a few reported cases of
      hepatogastric fistula after liver transarterial chemoembolization.

PMID- 22616502
TI  - [Pharmacogenomics in gastroenterologic diseases].
AB  - Pharmacogenomics is the study of genetic variations that produce a modification
      of the response to drugs. These variations are expressed as a different capacity
      for the metabolism or the transport of drugs, or a variable activity of drug
      receptors. Drug use in gastroenterology offers different examples of the use of
      pharmacogenomic analysis in the identification of the appropriate drug and drug
      dose for each individual patient. The use of proton pump inhibitors in the
      treatment of gastroesophagic reflux disease and Helicobacter pylori eradication
      may be optimized by the analysis of polymorphisms of the CYP2C19 gene.
      Additionally, the study of variants of IL28 helps in the identification of
      patients with more chances of response to the treatment of hepatitis C with
      interferon and ribavirin. The analysis of polymorphisms of the gene coding for
      the enzyme thiopurine methyl transferase (TPMT) helps in the reduction of the
      risks associated with the use of azathioprine in the treatment of inflammatory
      bowel disease. In this way, pharmacogenomics constitute not only a therapeutic
      tool that already shows an impact in the individualization of drug use in
      gastroenterology but also a tool with a great projection in the future.

PMID- 22616503
TI  - [The methodology course in career specialist].

PMID- 22616504
TI  - James M. Connelly: each challenge is an opportunity.

PMID- 22616505
TI  - What happens now with the Affordable Care Act?

PMID- 22616506
TI  - 5 ways to better understand costing for physician practices.

PMID- 22616507
TI  - Medical foundations: one model for hospital-physician alignment.
AB  - Some states that enforce a corporate practice of medicine prohibition have
      created medical foundation statutes allowing hospitals or health systems to own
      corporations providing physician services. Medical foundations may be useful in
      the coordination of care through employed or contracted physicians. Medical
      foundations that qualify as a tax-exempt entities have lower risks associated
      with tax-exempt rules as long as payments to physicians are reasonable and don't
      result in private inurement.

PMID- 22616508
TI  - Technology safeguards needed as security rule audits loom.
AB  - The Department of Health and Human Services will conduct security rule audits
      that will involve on-site visits and include: Compliance-focused interviews with
      key organizational leaders. Scrutiny of physical operations controls, especially
      regarding storage, maintenance, and use of protected health information.
      Assessment of organizational policies and procedures to ensure compliance with
      privacy and security rules. Identification of regulatory compliance areas of
      concern.

PMID- 22616510
TI  - George C. Halvorson: the future is connectivity.

PMID- 22616509
TI  - Understanding your capital options.
AB  - When planning capital expenditures, hospitals and health systems should
      understand the following financing considerations: Traditional fixed-rate tax
      exempt bonds; Variable-rate financing alternatives; Basel III Accord
      requirements; Direct tax-exempt bank loans; Total return swaps Taxable
      financings; Interest-rate swaps and collateral requirements

PMID- 22616511
TI  - Risks and rewards of variable-rate debt.
AB  - Hospital and health system finance leaders should position their organizations to
      participate in the variable-rate market. To this end, one important step is to
      establish the right baseline variable-rate exposure target for the organization
      based on its credit and risk profile. Leaders also should be thoroughly familiar
      with the available products and understand the circumstances (pricing, terms, and
      embedded risk) under which the organization would be willing to deploy them
      within the overall capital structure.

PMID- 22616512
TI  - Multi-track financing.
AB  - In today's uncertain economic environment, when seeking to finance a capital
      project, healthcare borrowers should adopt a multi-tracked funding strategy that
      permits them to change capital-funding routes quickly in response to changing
      circumstances. The multi-tracking process requires two stages prior to securing a
      commitment and beginning the closing process: due diligence and indication of
      interest. This process should present no material additional cost during these
      two stages, giving healthcare borrowers the flexibility to explore a variety of
      financing options.

PMID- 22616513
TI  - Strategies for healthcare facilities, construction, and real estate management.
AB  - Adventist HealthCare offers the following lessons learned in improving the value
      of healthcare facilities, construction, and real estate management: Use an
      integrated approach. Ensure that the objectives of the approach align the
      hospital or health system's mission and values. Embrace innovation. Develop a
      plan that applies to the whole organization, rather than specific business units.
      Ensure commitment of senior leaders.

PMID- 22616514
TI  - Developing healthcare facilities for a changing environment.
AB  - When approaching facility and real estate development, healthcare leaders should:
      Enhance clinical integration and ensure more patient-friendly facilities. Focus
      on a facility's business requirements and operating needs. Create a business plan
      that demonstrates how a project would help deliver better care at lower cost
      during a time of declining payment levels. Develop an approach that balances the
      needs of all stakeholders, including payers, staff, and patients.

PMID- 22616515
TI  - Hospital design and construction: song of the sirens.
AB  - Hospital and health system executives charged with overseeing a facility design
      and-build project should follow the examples of organizations that have
      successfully completed such projects. Here are just a few lessons learned from
      fruitful projects: Simplistic cost comparisons do not define value. Alternative
      design solutions offer a hospital the opportunity to test the value of its
      original design thinking. Functional designs reflect proven best practices.

PMID- 22616516
TI  - Physician relationships: make your first impression count.
AB  - Strategies for physician recruitment should include the following: Consider
      creating an in-house recruiting system to save money and to "own" the health
      system's first impression. Gain a competitive advantage by nurturing
      relationships with prospects over the long-term. Use innovative recruitment
      techniques, such as video interviewing and electronic reference checking, to
      better coordinate recruitment, follow-up, and mentoring. Make a new hire's job
      satisfaction and home life a top priority during the first 90 days of employment,
      and then plan regular follow-ups to maintain a positive relationship.

PMID- 22616517
TI  - Engaging staff with team-based performance sharing.
AB  - Team-based performance sharing (TPS) is a tool that hospitals can use to achieve
      higher levels of performance by tapping into innovative thinking within a unit's
      staff regarding opportunities to improve performance. In a recent pilot
      implementation of TPS, employees were able to share in the financial gains from
      recommended and approved improvements, as long as patient satisfaction remained
      above a certain specified threshold. Proposals for improvements were vetted by a
      dedicated crossfunctional team composed of unit staff, who had to be in full
      agreement regarding the merits of a proposal for it to be accepted.

PMID- 22616518
TI  - No satisfaction?

PMID- 22616519
TI  - What would you do? What should our new system's strategic priorities be post
      merger?

PMID- 22616520
TI  - Continued investment in healthcare IT critical.

PMID- 22616521
TI  - Governance: still at the top of the investment agenda.

PMID- 22616522
TI  - ROI from facility investment: quality and patient satisfaction.

PMID- 22616523
TI  - [Current principles of cholelithiasis prophylaxis in the practice of district
      physician].
AB  - The key task of the district physician is staged diagnostic search and clinical
      detection of functional disorders--conduction of laboratory tests and device
      investigations (in cholelithiasis patients--ultramicroscopic investigation of
      bile, x-ray methods, ultrasonography) to initiate prophylactic-therapeutic
      measures (medico-social, pharmacological and therapeutic-dietary).

PMID- 22616524
TI  - [Subjective sleep characteristics, apnea episodes and day drowse in patients with
      systolic cardiac failure: potential of clinicofunctional outpatient examination].
AB  - AIM: To characterize sleep apnea (SA) in patients with systolic cardiac failure
      (SCF) using respiratory monitoring, sleep quality and diurnal drowse
      questionnaires. MATERIAL AND METHODS: A total of 358 SCF outpatients with SA
      episodes were examined: 24 hour ECG and respiration monitoring, an analysis of
      diurnal drowse questionnaire survey, apnea and snoring self-appraisal. RESULTS:
      Significant SA episodes were registered in 15.1% of 358 patients (SA index 5 and
      more per hour). The episodes occurred significantly more frequently in patients
      with overweight and had high sensitivity and specificity. However no correlation
      was found with severity ofdiurnal drowse, sleep duration and age. SA risk was
      relatively high in patients with a history of snoring and nocturnal sleep apnea
      (2.95-2.79). The significance of the latter rose to 9.12-8.81 in SCF patients
      with normal myocardial mass index CONCLUSION: Subjective and objective sleep
      characteristics, except diurnal drowse, can be used for risk stratification in
      SCF patients with SA.

PMID- 22616525
TI  - [The role of day hospital in optimization of medical care for patients of a
      therapeutic department of an outpatient clinic].
AB  - Day hospital (DH) provides consultations and treatment for all referred patients
      according to standards of medical care quality. DH has facilities for therapeutic
      and gastroenterological patients. Treatment in DH is performed according to
      current standards which cover basic treatment of the diseases (documented
      medicines, duration of treatment). Efficacy of DH's use of the Standards of
      Diagnosis and Therapy of Acid-Dependent Diseases associated with Helicobacter
      pylori (standards of Moscow consensus) is used as illustration. As a result of
      treatment in DH 93% outpatients resumed their jobs, improvement occurred in 96.7%
      patients, a complete response was seen in 23%, 1.9% cases failed treatment. Most
      DH patients (83%) were satisfied with treatment given in DH and think it a
      convenient replacement of hospital stay.

PMID- 22616526
TI  - [Visits to the doctor because of illness or injury of the students of vocational
      schools who consume or do not consume psychoactive substances (comparative
      aspects)].
AB  - AIM: To elucidate what impact has the use of different narcotic drugs, alcohol
      and tobacco on the health of students and the risk of injuries. MATERIAL AND
      METHODS: We carried out a questionnaire survey of the first year students from
      all six vocational schools of Klaipeda (Lithuania) in 2004, 2006 and 2008. A
      total of 912 students (507 boys and 405 girls, mean age 17.5 years) were surveyed
      with an anonymous questionnaire. The findings were analysed with computer soft
      SPSS (SPSS 16.0 for Windows). RESULTS: The results showed that the use of any
      psychoactive substances is damaging to health, especially injection and club
      narcotic drugs. Adolescents addicted to any psychoactive substances more often
      than non-addicts visited doctor due to illness or injury during the last 12
      months. CONCLUSION: Adolescents on illegal drugs, especially boys on injectable
      narcotic drugs and girls on club drugs were at twice higher risk for disease or
      injury (odds ratio--OR--3.39, 95% confidence interval--CI--1.25 to 9.19, p =
      0.016 and OR--2.38, CI--1.35 to 4.20, p = 0.003, respectively). Tobacco and
      alcohol consumption did not significantly increase this risk with the exception
      of tobacco smoking girls. We think it happened because these two addictions are
      widely spread among large part of the boys from the vocational schools.

PMID- 22616527
TI  - [Optimal rehabilitation of patients with coronary heart disease in outpatient
      setting].
AB  - The problem of invalid rehabilitation in Russia is an important state task and
      dictates necessity of design of an effective state program of primary prevention
      of cardiovascular diseases. Common global practice of medico-social model is
      based on complex detailed medico-social aid. Rehabilitation of postmyocardial
      infarction patients consists of three phases (stages): hospital posthospital
      (readaptation) and postreconvalescent (supportive). The program includes
      physical, psychological and pharmacological rehabilitation. Departments of
      readaptation and medico-social rehabilitation provide effective conduction of all
      kinds of rehabilitation. The Moscow North-East Regional Administration has a rich
      experience in organization of departments of readaptation and medico-social
      rehabilitation. The departments practice an individual approach to the patients
      and work in a close contact with bureaus of medico-social commission of experts.
      Management of patients by cardiologist, rehabilitation specialist and outpatient
      clinic's physicians provides uninterrupted staged rehabilitation, timely
      correction of pharmacotherapy, early patient referral to invasive investigations
      and treatment of coronary heart disease. A course of rehabilitative measures
      lasts 2 months. Setting up departments of medico-social rehabilitation in
      outpatient clinics provides more effective use of money assigned by the state for
      social support of invalids.

PMID- 22616528
TI  - [Assessment of the quality of medical assistance for patients with acute ST
      elevation coronary syndrome for 2009-2010 in regions of the Russian Federation
      participating in the "vascular program" (by the data of the Russian ACS
      Register)].
AB  - AIM: To assess quality of medical assistance for patients with acute ST elevation
      coronary syndrome (aSTeCS) for the period from 2009 to 2010 in 23 administrative
      regions of the Russian Federation (RF) realizing the "vascular program". MATERIAL
      AND METHODS: We analysed management of aSTeCS patients treated in the regional
      vascular centers and/or primary vascular departments of 23 administrative regions
      of the RF for the period from January 1, 2009 to January 1, 2011. Mean age of the
      patients was 64 (56-75) years, 65.8% were males. For the above period computer
      medical information was available for 45407 acute coronary syndrome (ACS)
      patients, of them the diagnosis of aSTeCS was in 17514 patients. RESULTS: We
      found that most aSTeCS patients seek medical advice late, prehospital aspirin was
      prescribed only in 50-60% cases. Thrombolytic therapy (TLT) was performed, on the
      average, in 22 and 27% cases in 2009 u 2010, respectively A definite positive
      trend in TLT administration in 2009-2010 was seen only in 5 regions. In 2010,
      frequency of TLT conduction was below the evarage for all the sample in 8 regions
      of the RE Procedures of urgent percutaneous coronary intervention (UPCI) in 2009
      were made, on the average, in aSTeCS patients, in 2010--in 22,6%. A positive
      trend in application of UPCI in aSTeCS patients was registered in 9 RF regions.
      The number of UPCI procedures under 100 in 2010 was seen in 5 RF regions.
      CONCLUSION: CS Register provided data on application of high-tech treatment and
      pharmacotherapy in 2009 u 2010 in medical institutions of 23 RF regions realizing
      "vascular program".

PMID- 22616529
TI  - [Effects of anomalous rise of air temperature on population mortality].
AB  - Global climate warming for the last 10 years actualized the problem of mortality
      rise in some European countries in anomalous summer heat. Russia faced this
      problem in July-August 2010 when extreme heat entailed a significant elevation of
      mortality in 31 regions of the country primarily due to coronary heart disease
      and cerebrovascular diseases. The analysis of foreign researches has shown that
      old age and living in cities are leading risk factors of deat in anomalous heat.
      Experience of the European countries and USA evidences that stay in conditioned
      apartments and early referral for medical assistance are most effective death
      preventive measures in heat.

PMID- 22616530
TI  - [Systolic and diastolic intraventricular asynchrony of the left ventricular
      myocardium in patients with pacemaker].
AB  - AIM: To study intraventricular asynchrony and effects of pacemaker implantation
      on asynchrony severity in patients with rhythm and conduction disorders. MATERIAL
      AND METHODS: The study of 46 patients with cardiac arrhythmia (atrial
      fibrillation, sick sinus syndrome, AB-block of the third degree) included such
      examinations as echocardiography, tissue dopplerography (PWTDI) before pacemaker
      implantation and 7 days after it. Electromechanic systolic and diastolic
      myocardial asynchrony was assessed by intraventricular heterogeneity index (IHb,
      IHm, TSD) in 8 segments of the left ventricle (LV) at the basal and mean levels.
      Values obtained in examination of 32 healthy volunteers were considered normal.
      RESULTS: Parameters of systolic and diastolic asynchrony in patients with cardiac
      arrhythmia significantly differ from normal ones. Basal LV diastolic asynchrony
      was detected in 41-48% patients, systolic one--in 62-100%, systolodiastolic--in
      41% cases. Pacemaker implantation into the right heart significantly reduces LV
      systolic asynchrony while diastolic one was unaffected in an early postoperative
      period. The best sensitivity in detection of systolic asynchrony is achieved with
      TsSD index. Informative value of diastolic asynchrony parameters is much less
      than of the systolic one. CONCLUSION: Indices of systolic asynchrony (TsSD, IhbS,
      IhmS) can be used for heart condition control after pacemaker implantation.

PMID- 22616531
TI  - [Successful treatment of massive thrombosis of the vena cava inferior with
      nephrotic syndrome and chronic bilateral pulmonary artery thromboembolism in a
      patient with genetic thrombophilia].
AB  - A case is reported of a 23-year-old male patient who developed, after severe
      blunt injury of the lumbar region, massive thrombosis of the vena cava inferior
      (VCI), both renal veins, bilateral pulmonary artery thromboembolism (PATE),
      nephrotic syndrome (NS). In spite of anticoagulant therapy, the condition of the
      patient progressively aggravated for 1.5 year: thrombosis involved the ileac and
      femoral arteries on the right, thrombus floated in the right atrium with PATE
      recurrent episodes, pulmonary hypertension reached 120 mm Hg with formation of
      decompensated cor pulmnonale, proteinuria and hypoalbuminemia deteriorated,
      anasarca edema developed Multigenic thrombophilia was diagnosed (1 homozygous and
      5 heterozygous mutations). A radical one-stage operation was successful:
      thromboectomy from the VCI, right ileac and left renal veins,
      thrombendarterectomy from the pulmonary arteries, suture of the interatrial
      septum defect, installation of cava-filter After the operation pulmonary pressure
      lowered to 40-45 mm Hg, right heart volume normalized, immunosuppressive therapy
      with prednisolone and cyclosporine led to nephropathy remission. The discussion
      covers mechanisms and factors (including genetic) of thrombosis progression,
      correlations between intravascular thrombosis, NS and chronic glomerulonephritis
      (possible NS development due to bilateral thrombosis of the renal veins and
      nephropathy role in thrombosis progression), approaches to conservative and
      surgical treatment of such patients. Global experience in conduction of pulmonary
      thrombendarterectomy and thrombectomy from VCI is reviewed (one-stage operations
      were not described earlier).

PMID- 22616532
TI  - [Hypertension in pregnant women--a novel cardiorenal continuum].
AB  - AIM: To investigate cardiorenal correlations in pregnant patients with arterial
      hypertension. MATERIAL AND METHODS: Risk factors (RF), initial stages,
      progression, and final stage of both cardiovascular disease (CVD) and chronic
      kidney disease (CKD) were analysed in a cohort of 159 pregnant women with
      hypertensive disorders versus a cohort of 32 healthy pregnant controls.
      Cardiorenal continuum factors were investigated in patients with different ways
      of gestational hypertension (HT) diagnosis: 13 with isolated clinic HT (ICHT), 11
      -isolated ambulatory HT (IAHT), and 18--HT found by all three blood pressure (BP)
      measurement modalities (clinic, ambulatory, and home BP). RESULTS: A novel
      cardiorenal continuum exists in pregnant women with HT where chronic HT
      (essential HT) on the one hand and pre-eclampsia on the other hand may lead
      through the common RF and initial stages (subclinical organ damage) to the stage
      of progression (CVD, CKD) and to the final stage (cardiovascular events and renal
      failure). The number of RF signs of subclinical organ damage, and total
      cardiovascular risk progressively increase from the condition of being
      normotensive on clinic, home, and 24-hour definitions to the condition of being
      found hypertensive by one, two and all three BP measurement methods, forming the
      continuum "healthy pregnant women--ICHT--IAHT--gestational HT" in which each item
      is almost the same as the ones next to it but the last is very different from the
      first. CONCLUSION: Assessment of the cardiorenal state in all pregnant women
      allows to compose the cline "healthy pregnants--gestational HT--stage I essential
      HT--stage II essential HT--pre-eclampsia--essential HT with superimposed pre
      eclampsia" with growing risk of CVD and CKD and a potential danger of
      cardiovascular events (complications) and chronic renal failure.

PMID- 22616533
TI  - [Perspectives of molecular visualization in cardiology].
AB  - The lecture concerns prospects of molecular visualization in cardiology. The term
      molecular visualization, its aims and problems are characterized Methods of
      molecular visualization involve such non-invasive techniques as ultrasonic
      investigation, optic visualization, MR tomography, x-ray CT radionuclide
      examinations (single photon emission computed tomography and positron-emission
      tomography). The scope of the above methods and their limits in visualization of
      biomarker target molecules in different pathological processes on the molecular
      level, cardiovascular diseases (CVD) are outlined. The discussion covers various
      methodological approaches to molecular visualization of the processes associated
      with development and progression of atherosclerosis, visualization of
      atherosclerotic plaques of a high risk underlying myocardial infarction or
      stroke, thrombosis, inflammation, apoptosis, cardiac failure; with myocardial
      regeneration after myocardial infarction, angiogenesis and other conditions as
      well as assessment of effect of novel target approaches to CVD treatment. For
      each of the processes (atherosclerosis, thrombosis, angiogenesis, apoptosis, gene
      expression and other pathological conditions) biomarker target molecules are
      considered. Optimal among them are molecular targets with established biological
      and clinical significance, target-receptors or enzymes, contrast substances,
      molecular probes tropic to biomarker molecular targets having adequate affinity
      and pharmacodynamics which allows molecular visualization in clinical setting.
      The investigators are faced with many unsolved problems which can be studied with
      methods of molecular visualization.

PMID- 22616534
TI  - [New guidelines for hypertension in Russia--a priority of combined treatment].
AB  - This review provides an analysis of the results of Russian and foreign clinical
      trials that have shown a high antihypertensive efficacy and tolerability of
      combined medications containing fixed doses of perindopril and indapamide.

PMID- 22616535
TI  - [Renal affection in gout].
AB  - The study of the problem of impairment of the kidneys in gout is important
      because investigation of gout nephropathy specifies the role of hyperuricemia (a
      known risk factor) in development of renal damage, on the one side, and
      emphasizes the role of early detection of hyperuricemic genesis of nephropathy
      allowing prognosis improvement due to administration of uricostatic treatment, on
      the other side. Earlier data on tubulointerstitial lesion are now supplied with
      information on essential glomerular damage due to endothelial dysfunction in the
      presence of insulin resistance often associated with gout.

PMID- 22616536
TI  - [From classification medicine to clinical medicine (the end of the XVIII century-
      1870s) communication 5. Reforms in therapy in 1840s-1860s].
AB  - Reforms of therapy in 1840-1860s are considered: development of the methods of
      objective assessment of efficacy of some methods of treatment, appearance of
      experimental pharmacology, introduction of anasthesia.

PMID- 22616537
TI  - Clinical privileges: opening doors for APRNs.

PMID- 22616538
TI  - The "impaired" nurse--is it "breaking news" in your workplace?

PMID- 22616539
TI  - Nurses for breastfeeding: policy alert.

PMID- 22616540
TI  - History of autism.

PMID- 22616541
TI  - Waiver of the psychotherapist-patient privilege: implications for child custody
      litigation.
AB  - The psychotherapist-patient privilege, rooted in both common and statutory law,
      is predicated upon the public policy goal of protecting the reasonable
      expectation of privacy of individuals seeking psychotherapy. The privilege is not
      absolute, however. State and federal courts are far from uniform in determining
      how and when the privilege should be waived, in whole or in part, through
      implication, inadvertence or the affirmative action of the parties. In the family
      law context, the law that has evolved around the exercise of this privilege is
      even more complex as the needs of children add another wrinkle to the goal of
      balancing the imperative of confidentiality with the need for useful information
      that may be provided.

PMID- 22616542
TI  - PGTandMe: social networking-based genetic testing and the evolving research
      model.
AB  - The opportunity to use extensive genetic data, personal information, and family
      medical history for research purposes may be naturally appealing to the personal
      genetic testing (PGT) industry, which is already coupling direct-to-consumer
      (DTC) products with social networking technologies, as well as to potential
      industry or institutional partners. This article evaluates the transformation in
      research that the hybrid of PGT and social networking will bring about, and-
      highlighting the challenges associated with a new paradigm of "patient-driven"
      genomic research--focuses on the consequences of shifting the structure, locus,
      timing, and scope of research through genetic crowd-sourcing. This article also
      explores potential ethical, legal, and regulatory issues that arise from the
      hybrid between personal genomic research and online social networking,
      particularly regarding informed consent, institutional review board (IRB)
      oversight, and ownership/intellectual property (IP) considerations.

PMID- 22616543
TI  - Bending the health cost curve: the promise and peril of the Independent Payment
      Advisory Board.
AB  - Underlying today's and the future's health-care reform debate is a consensus that
      America's health-care financing system is in a slow-moving but deep crisis: care
      appears substandard in comparison with other advanced industrial countries, and
      relative costs are exploding beyond all reasonable measures. The Obama
      Administration's Patient Protection and Affordable Care Act (ACA) attempts to
      grapple with both of these problems. One of ACA's key instrumentalities is the
      Independent Payment Advisory Board-the IPAB, designed to discover and authorize
      ways to reduce the rate of growth of Medicare and other categories of health
      spending. The IPAB is a peril. Expert boards to perform regulatory tasks in the
      interest of efficiency and social goals always run a high risk of being captured
      by the industry they are supposed to regulate. Even should it succeed at its task
      of reducing the rate of growth of Medicare spending, who is to say that the
      reductions will not come at a heavy cost in reduced quantity and effectiveness of
      medical care? But the IPAB also has promise. The need for a better process than
      our current specialist-driven one to assign value to the medical services
      provided by Medicare is great. The bellwether status of Medicare payment systems
      means that commercial insurance consumers and payors would also benefit mightily
      from bringing more coherent, technocratic, and cost-effectiveness oriented logic
      to this process. And the current system of relative Medicare reimbursement rates
      is, in the judgment of many, currently well out of whack. We quail when we
      consider the magnitude of the tasks the IPAB faces--even its initial task.
      Nevertheless, we remain optimistic that this administrative agency will manage to
      bend the long-run healthcare cost curve and moderate future price increases.

PMID- 22616544
TI  - Quality of health care and the role of relationships: bridging the medico-legal
      divide.
AB  - This Article focuses on an often overlooked barrier to efforts to enhance the
      quality of health care: the relationship crisis that currently exists between
      physicians and patients. This state of affairs has resulted from the divide
      between the medical and legal worlds. The medical arena has understandably tended
      to view the doctor-patient relationship as a purely medical issue, ignoring the
      law's impact in generating and sustaining problematic relationship patterns. The
      legal world has yet to fully recognize this state of affairs, and the law's role
      in its evolution and persistence. We offer a relational approach to health-care
      law as a means of bridging the divide between the two disciplines. In the
      malpractice context, this would entail adopting a no-fault compensation scheme,
      which is committed to strengthening collaborative doctor-patient relations,
      enhancing patient safety and systemic learning, while providing adequate
      compensation.

PMID- 22616545
TI  - University opposition to unfettered research: a new bedfellow for biotech?
AB  - This Article examines university opposition to a proposed statutory exemption to
      infringement liability for basic genetic research and patient care. Gene
      patenting has allowed patentees to bar basic genetic research, slowing the
      progress of developing and administering diagnostics and gene-targeting
      therapeutics. Debates over the merits of gene patents have been heated, most
      recently leading to an unprecedented invalidation of several broad patents
      covering all variations and use of two genes linked to breast and ovarian
      cancers. More important, however (as this ruling was reversed in part), are
      proposed statutory exemptions to infringement liability. The Department of Health
      and Human Services' Secretary's Advisory Committee on Genetics, Health, and
      Society (SACGHS) has promulgated an exemption from liability for infringement
      that occurs in the course of research. This exemption would promote basic
      research by granting academic scientists unfettered access to genetic material.
      The proposal does not alter the patentability of gene sequences; it merely
      restricts patentees from using infringement threats to stop research.
      Surprisingly, the Association of University Technology Managers (AUTM), an
      organization responsible for promoting development of university research,
      opposes such an exemption. The AUTM alleges that the exemption would slow
      research by reducing the incentive for private firms to invest in upstream
      discoveries made in university laboratories. Yet the exemption would do the
      opposite: by opening the doors to research relating to any gene segment, a
      research exemption would accelerate basic research. Moreover, it would not affect
      collaboration with private industry: where there is potential to commercialize
      basic research, biomedical companies would continue to license the rights to
      university discoveries. Thus, the AUTM's motivations in opposing the proposed
      research exemption are suspect. They appear to reflect either a misunderstanding
      of the purpose behind granting property rights to publicly funded university
      research, or an improper alignment with industry goals.

PMID- 22616546
TI  - Catching flies with vinegar: a critique of the Centers for Medicare and Medicaid
      self-disclosure program.
AB  - This Article argues that the current approach of the Department of Health and
      Human Services and the Centers for Medicare and Medicaid Services (CMS) to
      enforcement of the Ethics in Patient Referrals Act (the "Stark Law") is
      unnecessarily punitive and discourages health-care providers from self-disclosing
      even very minor violations of the Stark Law. This Article suggests a number of
      specific changes to encourage provider self-disclosure and proposes that CMS
      create a demonstration project under the authority of the Patient Protection and
      Affordable Care Act to test the reforms. A demonstration project provides the
      perfect vehicle to prove that increased self-disclosure protocols for the Stark
      Law can decrease the government's costs of enforcement, improve program
      integrity, and encourage providers to deal responsibly with the inevitable minor
      lapses in compliance that arise in such an enormous government program as
      Medicare.

PMID- 22616547
TI  - Setting gender identity free: expanding treatment for transsexual inmates.

PMID- 22616548
TI  - Rehabilitating opioid regulation: a prescription for the FDA's next proposal of
      an opioid risk evaluation and mitigation strategy (REMS).

PMID- 22616549
TI  - Medical marijuana and the ADA: removing barriers to employment for disabled
      individuals.

PMID- 22616550
TI  - Water is a poor solvent for densely grafted poly(ethylene oxide) chains: a
      conclusion drawn from a self-consistent field theory-based analysis of neutron
      reflectivity and surface pressure-area isotherm data.
AB  - By use of a combined experimental and theoretical approach, a model poly(ethylene
      oxide) (PEO) brush system, prepared by spreading a poly(ethylene oxide)-poly(n
      butyl acrylate) (PEO-PnBA) amphiphilic diblock copolymer onto an air-water
      interface, was investigated. The polymer segment density profiles of the PEO
      brush in the direction normal to the air-water interface under various grafting
      density conditions were determined by using the neutron reflectivity (NR)
      measurement technique. To achieve a theoretically sound analysis of the
      reflectivity data, we used a data analysis method that utilizes the self
      consistent field (SCF) theoretical modeling as a tool for predicting expected
      reflectivity results for comparison with the experimental data. Using this data
      analysis technique, we discovered that the effective Flory-Huggins interaction
      parameter of the PEO brush chains is significantly greater than that
      corresponding to the theta condition in Flory-Huggins solutions (i.e., chi(PEO
      water)(brush chains)/chi(PEO-water)(theta condition) ~ 1.2), suggesting that
      contrary to what is more commonly observed for PEO in normal situations (chi(PEO
      water)(free chains)/chi(PEO-water)(theta condition) ~ 0.92), the PEO chains are
      actually not "hydrophilic" when they exist as polymer brush chains, because of
      the many body interactions that are forced to be effective in the brush
      situation. This result is further supported by the fact that the surface
      pressures of the PEO brush calculated on the basis of the measured chi(PEO-water)
      value are in close agreement with the experimental surface pressure-area isotherm
      data. The SCF theoretical analysis of the surface pressure behavior of the PEO
      brush also suggests that even though the grafted PEO chains experience a poor
      solvent environment, the PEO brush layer exhibits positive surface pressures,
      because the hydrophobicity of the PEO brush chains (which favors compression) is
      insufficient to overcome the opposing effect of the chain conformational entropy
      (which resists compression).

PMID- 22616551
TI  - Effects of integrin-linked kinase on human corpus cavernosum smooth muscle cell
      cytoskeletal organisation.
AB  - We investigated the effects of integrin-linked kinase (ILK) on the in vitro
      attachment, spreading, migration and microfilament dynamics of human corpus
      cavernosum smooth muscle cells. ILK small interfering RNA (siRNA) was used to
      transfect human corpus cavernosum smooth muscle cells; and cell attachment,
      spreading and migration were assessed. Additionally, microfilament dynamics were
      evaluated using Alexa Fluor 488 and phalloidin staining. We found that ILK gene
      knock-down significantly inhibited human corpus cavernosum smooth muscle cell
      attachment, spreading and migration. Moreover, blocking the expression of ILK
      disturbed actin cytoskeleton reorganisation and morphology in human corpus
      cavernosum smooth muscle cells. These results show that the targeting of ILK with
      siRNA significantly inhibited cell attachment, spreading, migration and
      microfilament dynamics in human corpus cavernosum smooth muscle cells. These
      findings indicate that ILK might be a potential therapeutic molecular target for
      the treatment of erectile dysfunction.

PMID- 22616552
TI  - ERCC1 as a biomarker for bladder cancer patients likely to benefit from adjuvant
      chemotherapy.
AB  - BACKGROUND: The role of adjuvant chemotherapy and the value of molecular
      biomarkers in bladder cancer have not been determined. We aimed to assess the
      predictive and prognostic values of excision repair cross-complementation 1
      (ERCC1) in identifying appropriate patients who may potentially benefit from
      adjuvant chemotherapy for bladder cancer. METHODS: A retrospective analysis was
      performed on 93 patients with completely resected transitional cell carcinoma of
      the bladder. ERCC1 expression was assessed by immunohistochemistry. ERCC1
      expression was analyzed in 57 patients treated with adjuvant gemcitabine plus
      cisplatin chemotherapy and 36 who were not treated. RESULTS: Among 93 patients,
      ERCC1 expression was positive in 54 (58.1%) and negative in 39 (41.9%). ERCC1
      positivity was significantly associated with longer survival (adjusted hazard
      ratio for death, 0.12, 95% confidence interval [CI] 0.014-0.99; P = 0.049) in the
      group without adjuvant chemotherapy while ERCC1 positivity was associated with
      shorter survival among patients who have received adjuvant chemotherapy (adjusted
      hazard ratio for death, 2.64; 95% CI 1.01-6.85; P = 0.047). Therefore, clinical
      benefit from adjuvant chemotherapy was associated with ERCC1 negativity as
      measured by overall survival (test for interaction, P = 0.034) and by disease
      free survival (test for interaction, P = 0.20). CONCLUSIONS: Among patients with
      completely resected transitional cell carcinoma of the bladder, those with ERCC1
      negative tumors seemed to benefit more from adjuvant gemcitabine plus cisplatin
      chemotherapy than those with ERCC1-positive tumors. Future prospective,
      randomized studies are warranted to confirm our findings.

PMID- 22616553
TI  - Anti-inflammatory effects of moxifloxacin on rat airway smooth muscle cells
      exposed to allergen: Inhibition of extracellular-signal-regulated kinase and
      nuclear factor-kappaB activation and of interleukin-8 and eotaxin synthesis.
AB  - BACKGROUND AND OBJECTIVE: Moxifloxacin (MXF) has been shown to possess
      immunomodulatory properties in addition to its antimicrobial effects. We
      investigated the effects of MXF on cytokine secretion and signal transduction
      mechanisms in naive control and allergen-exposed airway smooth muscle cell (ASMC)
      stimulated with tumour necrosis factor (TNF)-alpha. METHODS: An animal model was
      established. ASMC was derived from rat airway tissue and cultured in vitro, then
      incubated with 10 ng/mL of TNF-alpha. Interleukin (IL)-8 and eotaxin secretion
      were measured by enzyme-linked immunosorbent assay, and activation of
      extracellular-signal-regulated kinase (ERK)1/2 and nuclear factor (NF)-kappaB p65
      was measured by western blotting, with or without the addition of MXF (20 ug/mL)
      and/or dexamethasone (DXM) (10(-6)  M). RESULTS: Baseline IL-8 and eotaxin
      secretion did not differ between control and allergen-exposed cells. Stimulation
      with TNF-alpha increased IL-8 and eotaxin secretion, with increased IL-8
      secretion by allergen-exposed compared with naive control ASMC, post-TNF-alpha
      stimulation (P = 0.001). Baseline phosphorylation of ERK1/2 (p-ERK1/2) and NF
      kappaB p65 was higher in allergen-exposed than in control ASMC. TNF-alpha
      increased p-ERK1/2 and NF-kappaB p65 levels, with higher levels in allergen
      exposed ASMC, post-TNF-alpha stimulation (P < 0.001). MXF and the combination of
      MXF with DXM suppressed the secretion of IL-8 and eotaxin, but DXM alone did not
      affect IL-8, post-TNF-alpha stimulation (P > 0.05). MXF, DXM and the combination
      of MXF with DXM inhibited TNF-alpha-stimulated p-ERK1/2 and NF-kappaB p65 levels
      by 34, 40 and 62%, and 33, 38 and 64%, respectively. CONCLUSIONS: MXF suppressed
      the secretion of pro-inflammatory cytokines by allergen-exposed rat ASMC, partly
      by inhibiting NF-kappaB and ERK activation. DXM may have additional or
      synergistic effects with MXF.

PMID- 22616555
TI  - Preface to the colloidal nanoplasmonics special issue.

PMID- 22616554
TI  - Halogenated spirotetronates from Actinoallomurus.
AB  - Two new members of the spirotetronate class, nai414-A and nai414-B, were
      discovered and isolated from an Actinoallomurus sp. Their structures were
      established by 1D and 2D NMR, UV, and MS analyses and by chemical degradation.
      They showed antimicrobial and antitumor activity against Gram-positive bacteria
      and against human microvascular endothelial cells, respectively. Substituting
      bromide for chloride ions in the growth medium afforded mono- and dibrominated
      derivatives.

PMID- 22616556
TI  - The value of environmental information without control of subsequent decisions.
AB  - The standard value of information approach of decision analysis assumes that the
      individual or agency that collects the information is also in control of the
      subsequent decisions based on the information. We refer to this situation as the
      "value of information with control (VOI-C)." This paradigm leads to powerful
      results, for example, that the value of information cannot be negative and that
      it is zero, when the information cannot change subsequent decisions. In many real
      world situations, however, the agency collecting the information is different
      from the one that makes the decision on the basis of that information. For
      example, an environmental research group may contemplate to fund a study that can
      affect an environmental policy decision that is made by a regulatory
      organization. In this two-agency formulation, the information-acquiring agency
      has to decide, whether an investment in research is worthwhile, while not being
      in control of the subsequent decision. We refer to this situation as "value of
      information without control (VOI-NC)." In this article, we present a framework
      for the VOI-NC and illustrate it with an example of a specific problem of
      determining the value of a research program on the health effects of power
      frequency electromagnetic fields. We first compare the VOI-C approach with the
      VOI-NC approach. We show that the VOI-NC can be negative, but that with high
      quality research (low probabilities of errors of type I and II) it is positive.
      We also demonstrate, both in the example and in more general mathematical terms,
      that the VOI-NC for environmental studies breaks down into a sum of the VOI-NC
      due to the possible reduction of environmental impacts and the VOI-NC due to the
      reduction of policy costs, with each component being positive for low
      environmental impacts and high-quality research. Interesting results include that
      the environmental and cost components of the VOI-NC move in opposite directions
      as a function of the probability of environmental impacts and that VOI-NC can be
      positive, even though the probability of environmental impacts is zero or one.

PMID- 22616557
TI  - [3 + 2]-dipolar cycloaddition reactions of an N-heterocyclic carbene boryl azide.
AB  - Thermal 1,3-dipolar cycloaddition reactions of 1,3-bis(2,6
      diisopropylphenyl)imidazol-2-ylidene dihydridoboron azide occur smoothly with
      alkynes, nitriles, and alkenes bearing electron-withdrawing groups. New, stable
      NHC-boryl-substituted triazoles, tetrazoles, and triazolidines are formed in good
      to excellent yields.

PMID- 22616558
TI  - Potential application of IDH1 and IDH2 mutations as prognostic indicators in non
      promyelocytic acute myeloid leukemia: a meta-analysis.
AB  - Recurrent mutations of isocitrate dehydrogenase isoforms 1 and 2 (IDH1 and IDH2)
      have recently been studied in adult patients with acute myeloid leukemia (AML). A
      meta-analysis was performed to demonstrate their controversial prognostic
      impacts. The associations of IDH1 or IDH2 mutations with other molecular
      abnormalities were also investigated. In patients with AML, IDH1/2 mutations were
      significantly associated with normal karyotype and isolated trisomy 8 (p < .05).
      After adjusting for well-studied prognostic factors, IDH1 mutation seems to be
      associated with subtle but significantly inferior event-free survival (EFS) (p =
      0.02) and possible adverse overall survival (OS) (p = 0.13) in patients with AML,
      especially in the favorable genotype subset with mutated NPM1 but without FLT3
      ITD mutation (p < 0.05). Longer OS (p = 0.01) and better EFS tendency (p = 0.18)
      are implicated in patients with IDH2 mutations, which suggests that IDH2
      mutations appear to confer a favorable prognosis. Moreover, IDH1 and IDH2
      mutations may play a more important role in abnormal cytogenetics subgroups such
      as isolated trisomy 8. Screening of IDH1/2 mutations could help to identify
      patients at high risk within some subsets of AML.

PMID- 22616559
TI  - The first total synthesis of apigenin 7-O-beta-D-cellobiosyl-4'-O-beta-D
      glucopyranoside isolated from Salvia uliginosa.
AB  - The first total synthesis of apigenin 7-O-beta-D-cellobioside (5) and apigenin 7
      O-beta-D-cellobiosyl-4'-O-beta-D-glucopyranoside (8), which were isolated from
      petals of Salvia patens and Salvia uliginosa, were achieved in four and six steps
      and 76% and 57%, respectively, overall yield, from naringenin (1). The total
      synthesis contained two-glycosylation, acetylation, oxidation, selective
      deacetylation and deprotection steps. Although this route contained six steps,
      the targeted compounds were obtained with higher yields and easier purifications
      than other synthetic methods.

PMID- 22616560
TI  - Community health-care staff's experiences of support to prevent type 2 diabetes
      among people with psychosis: an interview study with health staff.
AB  - The aim of the study was to describe mental health staff experiences of giving
      support to prevent type 2 diabetes mellitus (DM) among people with psychosis in
      community psychiatry. A qualitative interview study with a purposeful sample of
      12 community health staff was conducted. Data were analysed using qualitative
      content analysis. The results show how staff reported continuously supporting
      people with psychosis to adapt to healthy lifestyles, but stated that support is
      not given until after a person becomes overweight or is diagnosed with type 2 DM.
      Support was described as a never-ending process of motivation facing many
      reverses. Individually-adapted support given in practical situations was
      perceived as most successful. Cooperation between health-care organizations was
      seen as essential, but inadequate. Limitations in income and social network, and
      easy access to fast food and alcohol, were seen as obstacles to support. The
      results indicate that community health staff are in a position to make a
      considerable impact in motivating and supporting healthy lifestyle changes in
      practical situations in daily life among people with psychosis. This study raises
      awareness of how community health staff's support can be useful when developing
      nursing skills and health-care plans for people with psychosis.

PMID- 22616561
TI  - Novel oral anticoagulants: focus on the direct factor Xa inhibitor darexaban.
AB  - INTRODUCTION: Inhibition of the pathways of anticoagulation is widely used for
      the prevention and treatment of arterial and venous thrombosis. Vitamin K
      antagonists (VKAs) have been the mainstay of oral anticoagulation for more than
      60 years. Their safety and effectiveness have been established in multiple
      clinical trials, for a variety of clinical indications. However, there are
      several limitations to the use of VKAs including delayed onset of action and
      dosage titration, numerous food and drug interactions and need for regular
      laboratory monitoring. To overcome some of the limitations of traditional agents,
      new oral anticoagulants (OACs) have been developed and evaluated. AREAS COVERED:
      In the present review article, the pharmacokinetic properties of darexaban are
      presented, along with the available preliminary clinical data. The performance of
      darexaban in respect to safety and efficacy compared with its competitors is
      further discussed. EXPERT OPINION: Darexaban is a potent direct factor Xa
      inhibitor that demonstrated impressive pharmacokinetic properties in pre-clinical
      studies. It was further successfully evaluated in the ONYX program for the
      prevention of venous thromboembolism in patients undergoing hip replacement.
      Finally, in the Phase II RUBY-1 trial, darexaban was tested on the top of
      standard antiplatelet therapy for the prevention of ischemic events in acute
      coronary syndrome (ACS) patients. Despite the fact that darexaban had a
      relatively uneventful clinical evaluation program, its further development was
      recently discontinued. This decision could probably reflect the non-favorite
      results in commercially attractive indications, such as secondary prevention post
      ACS and the increased competition for less common or short-term indications such
      stroke prevention in AF or VTE prophylaxis respectively.

PMID- 22616562
TI  - Structural characterization of moganite-type AlPO4 by NMR and powder X-ray
      diffraction.
AB  - Structural characterization of a new high-pressure AlPO(4) phase synthesized at 5
      GPa and 1500  degrees C is reported. The phase is monoclinic (P2/a) with a =
      8.7437(1) A, b = 4.8584(1) A, c = 10.8600(2) A, beta = 90.124(1) degrees  (Z =
      6). (31)P MAS NMR and two-dimensional (2D) (27)Al triple-quantum (3Q) MAS NMR
      revealed that it contains two tetrahedral P sites of 1:2 abundance ratio, and two
      tetrahedral Al sites with 1:2 ratio. 2D (31)P dipolar-recoupled double-quantum
      (DQ) MAS NMR and (27)Al -> (31)P dipolar-based (through-space) and J coupling
      based (through-bond) 3Q-heteronuclear correlation (HETCOR) experiments provided
      direct information on the linkages of these sites. The crystal structure was
      solved and refined from synchrotron powder X-ray diffraction data utilizing the
      information from NMR. The phase is isostructural to moganite, a rare SiO(2)
      polymorph, and its structure can be derived from the latter via an ordered
      replacement of tetrahedral Si sites by Al and P. The NMR parameters of the phase
      were also calculated by first-principles method, which are consistent with those
      observed. Contrary to the other moganite phases known to date (i.e., SiO(2) and
      PON), moganite-AlPO(4) has a higher-pressure stability field than the
      corresponding quartz phase. This is the first moganite-type phase found in the
      ABX(4) system.

PMID- 22616563
TI  - Salvage peripheral extracorporeal membrane oxygenation using Cobe Revolution((r))
      centrifugal pump as a bridge to decision for acute refractory cardiogenic shock.
AB  - OBJECTIVES: Acute refractory cardiogenic shock with early multisystem organ
      failure has a poor outcome without mechanical circulatory support. We review our
      experience with emergent peripheral cardiopulmonary support as a bridge to
      decision in these patients. METHODS: A retrospective review from January 2009
      through December 2010 was conducted of 26 consecutive adult patients at a single
      institution with acute refractory cardiogenic shock who underwent salvage
      peripheral cardiopulmonary support. RESULTS: There were 18 men and 8 women with a
      mean age of 54 years (range 18 to 76). Indications for support: acute myocardial
      infarction (n = 16), decompensated chronic heart failure (n = 2), refractory
      arrhythmic arrest (n = 3), acute valvular pathology (n = 4), and unknown (n = 1).
      Patients with primary postcardiotomy shock were excluded. Median duration of
      support was 3 days (range 1 to 14). Decisions included: withdraw of support (n =
      4), recovery (n = 5), and bridge to a procedure (n = 17). The procedures were
      percutaneous coronary intervention (n = 4), left ventricular assist device (n =
      9), heart transplantation (n = 1), and miscellaneous cardiac surgery (n = 3).
      Overall survival to discharge was 65%. In the recovery and bridge to a procedure
      group, 78% were discharged from the hospital and survival at three months was
      72%. CONCLUSIONS: Salvage peripheral cardiopulmonary support is a useful tool to
      rapidly stabilize acute refractory cardiogenic shock permitting an assessment of
      neurologic and end-organ viability.

PMID- 22616564
TI  - Lack of pregnancy loss history Mars depression study.

PMID- 22616565
TI  - Combinatorial strategies in fluorescent probe development.

PMID- 22616566
TI  - Quality of life of people living with HIV.
AB  - HIV infection is a global growing pandemic, and it is considered a public health
      problem. Treatment advances improved survival rates for HIV-infected individuals,
      although not always with a good quality of life (QoL). The aim of this study was
      to assess the QoL of people living with HIV (PLHIV) in the city of Sao Jose,
      Brazil. A cross-sectional study was performed involving a convenience sample of
      85 individuals. Self-administered questionnaires were used to collect
      sociodemographic information, treatment length and period of infection. The
      WHOQoL-HIV-Bref instrument was used to assess QoL. The collected data were first
      described in proportions, means, median and percentiles. Chi-square test or
      Fisher's exact test was used to test association between the perception of poor
      QoL taking the first quartile of the distribution of values with gender, age,
      education level, marital status, period of diagnosis, infection status, self
      rated health status and believing to be ill or not. The p values were established
      at <0.05. The found mean score of WHOQoL-HIV-Bref was 14.1 (SD = 2.9). Lower
      education level (p=0.011) and believing to be ill (p<0.001) were associated with
      poor QoL. Also lower education level was associated with poor QoL in the
      psychological (p=0.020) and environment (p=0.047) domains; being diagnosed with
      HIV infection within the past five years (p=0.029) was found to be associated
      with poor QoL in the social relationships domain; and believing to be ill was
      associated with all domains (physical: p<0.001; psychological: p=0.022; level of
      independence: p=0.009; social relationships: p=0.009; environment: p=0.005; and
      spirituality/religion/personal beliefs: p=0.021). It could be concluded that in
      general, PLHIV have a good QoL. A poor QoL was associated mainly with lower
      education level and when they believe to be ill.

PMID- 22616567
TI  - Decompression of benign orbital apex lesion via medial endoscopic approach.
AB  - The use of endoscopic orbital and optic nerve decompression for traumatic optic
      neuropathy and dysthyroid orbitopathy have been well documented; however, reports
      on endoscopic decompression for benign orbital apex lesions are scarce. The
      records of two patients who underwent endoscopic decompression of the bony orbit
      for progressive visual loss were reviewed. Patient 1 had fibrous dysplasia and
      presented with headache and visual field defects. Patient 2 had sphenoid wing
      meningioma and multiple previous attempts of transcranial tumor resection and
      orbital decompression. Both had progressive visual deterioration and ultimately
      underwent transnasal endoscopic orbital decompression. Post-operatively, both
      patients had subjective and objective improvement in visual function and
      compressive symptoms. No complications from the endoscopic decompression were
      observed in both patients. Transnasal endoscopic approach may be a viable option
      for decompression of benign orbital apex lesions.

PMID- 22616568
TI  - Simultaneous determination of five active compounds in chimonanthus nitens by
      double-development HPTLC and scanning densitometry.
AB  - BACKGROUND: Chimonanthus nitens (family Calycanthaceae), Shanlamei in Chinese, is
      an unique species in China. The extract of dried leaves of Chimonanthus nitens
      has anti-inflammatory, antipyretic and antitussive effects. Terpenes, coumarins,
      and flavonoids are usually regarded as the main active components. Therefore,
      simultaneous determination of these compounds is very important to control the
      quality of Chimonanthus nitens. RESULTS: A double-development TLC method was
      developed for simultaneous analysis of five compounds in Chimonanthus nitens. The
      chromatography was performed on silica gel 60 plate with chloroform-methanol
      (9?1, v/v) and petroleum ether-ethyl acetate (10?1, v/v) as mobile phase for
      twice development. Their characteristic TLC profiles were observed under UV light
      at 365 nm and the bands were then revealed by reaction with 1% vanillin-H2SO4
      solution. Quantification of three monoterpenes was achieved by densitometry at
      545 nm (beta-caryophyllene) or 606 nm (cineole and linalool). Two coumarins
      (scopoletin and scoparone) were determined by densitometry at 340 nm with filter
      wavelength of 370 nm. The investigated compounds had good linearity (R2 >0.99)
      within test ranges. CONCLUSIONS: The developed double-development TLC method is
      helpful to control the quality of Chimonanthus nitens, which is simple and
      accurate.

PMID- 22616569
TI  - The effects of combined glucose-electrolyte and sodium bicarbonate ingestion on
      prolonged intermittent exercise performance.
AB  - This study examined the effects of combined glucose and sodium bicarbonate
      ingestion prior to intermittent exercise. Ninemales (mean +/- s age 25.4 +/- 6.6
      years, body mass 78.8 +/- 12.0 kg, maximal oxygen uptake (VO2 max)) 47.0 +/- 7 ml
      . kg . min(-1)) undertook 4 * 45 min intermittent cycling trials including 15 *
      10 s sprints one hour after ingesting placebo (PLA), glucose (CHO), sodium
      bicarbonate (NaHCO3) or a combined CHO and NaHCO3 solution (COMB). Post ingestion
      blood pH (7.45 +/- 0.03, 7.46 +/- 0.03, 7.32 +/- 0.05, 7.32 +/- 0.01) and
      bicarbonate (30.3 +/- 2.1, 30.7 +/- 1.8, 24.2 +/- 1.2, 24.0 +/- 1.8 mmol . l(-1))
      were greater for NaHCO3 and COMB when compared to PLA and CHO, remaining elevated
      throughout exercise (main effect for trial; P < 0.05). Blood lactate
      concentration was greatest throughout exercise for NaHCO3 and COMB (main effect
      for trial; P < 0.05). Blood glucose concentration was greatest 15 min post
      ingestion for CHO followed by COMB, NaHCO3 and PLA (7.13 +/- 0.60, 5.58 +/- 0.75,
      4.51 +/- 0.56, 4.46 +/- 0.59 mmol . l(-1), respectively; P < 0.05).
      Gastrointestinal distress was lower during COMB compared to NaHCO3 at 15 min post
      ingestion (P < 0.05). No differences were observed for sprint performance between
      trials (P = 1.00). The results of this study suggest that a combined CHO and
      NaHCO3 beverage reduced gastrointestinal distress and CHO availability but did
      not improve performance. Although there was no effect on performance an
      investigation of the effects in more highly trained individuals may be warranted.

PMID- 22616570
TI  - Synthesis and characterization of soybean-based hydrogels with an intrinsic
      activity on cell differentiation.
AB  - The successful regeneration of large defects in traumatized and diseased tissues
      depends on the availability of biodegradable and bioactive biomaterials able to
      guide the tissue during its repair by offering both a physical support and a
      control of its biological mechanisms. Recently, a novel class of natural,
      biodegradable biomaterials has been obtained by the thermosetting of defatted soy
      curd. These biomaterials have been shown to regulate the activity of both tissue
      and inflammatory cells. Here, soybean-based hydrogels with different
      physicochemical properties and bioactivity have been obtained with a relatively
      simple and highly reproducible processing method. The content of the different
      soy components (e.g., the isoflavones) was tuned varying the solvent system
      during the extraction procedure, while variations in the material crosslinking
      provided either loose hydrogels or a bioglue. The biomaterials obtained can be
      used as either bioadhesives or injectable formulations in regenerative medicine
      as they were shown to stimulate the synthesis of collagen by fibroblasts and the
      formation of mineralized bone noduli by osteoblasts.

PMID- 22616571
TI  - Influence of anions in silver supramolecular frameworks: structural
      characteristics and sorption properties.
AB  - The complexation of a preorganized thioether-functionalized bis(pyrazolyl)methane
      ligand (L) with silver precursors produces supramolecular structures organized at
      two hierarchical levels: [AgL](6)(X)(6) metal-organic cyclic hexamers and their
      organization in 3D architectures. The cyclic toroidal hexamers of 22-26 A
      external diameter are found to be stable already in solution before self-assembly
      into the crystalline state. In the 3D lattice, the hexameric building block are
      arranged in different highly symmetric space groups as a function of a variety of
      anions (cubic Fd3 with PF(6)(-) or BF(4)(-) and rhombohedral R3 with CF(3)SO(3)(
      ) or NO(3)(-)) and form cavities with the geometrical shapes of Platonic solids
      (tetrahedron and octahedron) that can be occupied by a variety of solvent
      molecules. Upon evacuation, cubic crystals can produce stable frameworks with
      permanent porosity, which can absorb reversibly several vapors, CO(2) and CH(4).

PMID- 22616572
TI  - Predictive factors for residual disease in re-excision specimens after breast
      conserving surgery.
AB  - Local recurrence is an issue of concern after breast-conserving therapy and
      removing the primary tumor with negative surgical margins is the most important
      determinant of local recurrence. However, some patients with positive margins
      after initial surgery will have no residual tumor in the re-excision specimen. To
      avoid unnecessary re-excisions, factors predicting residual disease in re
      excision material should be determined. This study aimed to determine the
      predictive factors for residual disease in the re-excision material in a
      homogeneous group of patients with positive margins and only invasive ductal
      carcinoma. Breast cancer patients treated between 2005 and 2008 with breast
      conserving surgery and subsequent re-excisions due to positive surgical margins
      after initial surgery were included in the study. Patients were divided into two
      groups as those with and without residual disease in the re-excision material.
      One hundred and four breast cancer patients were included in the study. Forty
      seven patients (45.2%) had residual tumor in re-excision specimen. Patient
      characteristics such as age (p = 0.42) and physical findings (p = 1.0) and
      specimen volume (p = 0.24), tumor grade (p = 0.33), estrogen (p = 1.0), and
      progesterone (p = 0.37) receptor status, axillary lymph node metastases (p =
      0.16), extensive intraductal component (p = 0.8), and lymphovascular invasion (p
      = 0.064) were found as insignificant factors for predicting residual tumor. Large
      tumor size (>3 cm) (p = 0.026), human epidermal growth factor receptor2 (HER2)
      positivity (p = 0.013), and tumor to specimen volume ratio of >70% (p = 0.002)
      significantly increased the probability of finding residual disease after re
      excision. In multivariate analysis, HER2 positivity (p = 0.046) and tumor to
      specimen volume ratio of >70% (p = 0.006) independently predicted the presence of
      residual disease. As a result, in patients with HER2 positive tumors larger than
      3 cm, larger volume of breast tissue around the tumor should be removed to
      decrease the number of re-excisions due to positive surgical margins.

PMID- 22616573
TI  - First case of donor transmitted non-leukemic promyelocytic sarcoma.

PMID- 22616574
TI  - The Altar Machine in the Church Mother of Gangi (Palermo, Italy). Interpretation
      of the past uses, scientific investigation and preservation challenge.
AB  - BACKGROUND: The aim of this work was to study the Altar Machine in the Church
      Mother of Gangi, a little town near Palermo (Italy) regarding the history, the
      technical manufacture, the constitutive materials and the state of
      preservation.The Altar Machine was dated back to the second half of the 18th
      century; it is constituted by carved and painted wood, a complex system of winch
      and pulleys allows move various statues and parts of the Machine in accordance
      with the baroque scenography machineries. RESULTS: The observation and survey of
      the mechanisms allowed formulate hypothesis on a more ancient mode of operation
      of the Altar Machine.Laboratory analysis revealed the presence of many
      superimposed layers constituted by several different materials (protein binders,
      siccative oils, natural terpene resins, shellac, calcium carbonate, gypsum, lead
      white, brass, zinc white, iron oxides) and different wood species employed for
      the original and restoration elements of the Machine. This is due to a continuous
      usage of the object that has got a demo-ethno-anthropological
      significance.Microclimate monitoring (relative humidity RH and temperature T) put
      in evidence that most of the data fall outside the tolerance intervals, i.e. the
      RH and T limits defined by the international standards. In particular, T values
      were generally high (out of the tolerance range) but they appeared to be quite
      constant; on the other hand RH values fell almost always inside the tolerance
      area but they often exhibited dangerous variations. CONCLUSIONS: The
      characterization of the constitutive materials provided useful information both
      to support the dating of the Machine proposed by the inscription and to obtain a
      base of data for a possible conservation work.The microclimate monitoring put in
      evidence that the temperature and relative humidity values are not always
      suitable to correctly preserve the artefact. The careful in situ investigation
      confirmed an on-going climate induced damage to the Altar Machine that,
      associated to the deterioration caused by its usage, may have dramatic
      consequences on this unique and peculiar work of art.The results of this work
      will have potential implications in the near future regarding a probable
      conservation project on the Machine.

PMID- 22616575
TI  - Characterization of a dynamic string method for the construction of transition
      pathways in molecular reactions.
AB  - We explore the theoretical foundation of different string methods used to find
      dominant reaction pathways in high-dimensional configuration spaces. Pathways are
      assessed by the amount of reactive flux they carry and by their orientation
      relative to the committor function. By examining the effects of transforming
      between different collective coordinates that span the same underlying space, we
      unmask artificial coordinate dependences in strings optimized to follow the free
      energy gradient. In contrast, strings optimized to follow the drift vector
      produce reaction pathways that are significantly less sensitive to
      reparameterizations of the collective coordinates. The differences in these paths
      arise because the drift vector depends on both the free energy gradient and the
      diffusion tensor of the coarse collective variables. Anisotropy and position
      dependence of diffusion tensors arise commonly in spaces of coarse variables,
      whose generally slow dynamics are obtained by nonlinear projections of the
      strongly coupled atomic motions. We show here that transition paths constructed
      to account for dynamics by following the drift vector will (to a close
      approximation) carry the maximum reactive flux both in systems with isotropic
      position dependent diffusion and in systems with constant but anisotropic
      diffusion. We derive a simple method for calculating the committor function along
      paths that follow the reactive flux. Lastly, we provide guidance for the
      practical implementation of the dynamic string method.

PMID- 22616577
TI  - Cytotoxicity of semisynthetic acetal triterpenes from one-pot vicinal diol
      cleavage following by lactolization: reaction promoted by NaIO4/SiO2 gel in THF.
AB  - In situ C-C bond cleavage of vicinal diol following by the lactolisation resulted
      from separated treatment of Arjunolic acid (1), 24-hydroxytormentic acid (2) and
      3-O-beta-D-glucopyranosylsitosterol (3) with sodium periodate and silica gel in
      dried THF according to the strategic position of hydroxyl functions in the
      molecule. The reaction led to a lactol pentacyclic triterpenes 1A, 2A and a
      bicyclotriacetal of beta-sitosterol 3A. These products were further acetylated
      and the cytotoxicity of all molecules was evaluated against human fibrosarcoma
      HT1080 cancer cells lines.

PMID- 22616576
TI  - Developing an algorithm to identify people with Chronic Obstructive Pulmonary
      Disease (COPD) using administrative data.
AB  - BACKGROUND: An important prerequisite for the Chronic Care Model is to be able to
      identify, in a valid, simple and inexpensive way, the population with a chronic
      condition that needs proactive and planned care. We investigated if a set of
      administrative data could be used to identify patients with Chronic Obstructive
      Pulmonary Disease in a Danish population. METHODS: Seven general practices were
      asked to identify patients with known Chronic Obstructive Pulmonary Disease in
      their practices. For the 266 patients (population A), we used administrative data
      on hospital admissions for lung-related diagnoses, redeemed prescriptions for
      lung-diseases drugs and lung- function tests combined to develop an algorithm
      that identified the highest proportion of patients with Chronic Obstructive
      Pulmonary Disease with the fewest criteria involved. We tested nine different
      algorithms combining two to four criteria. The simplest algorithm with highest
      positive predictive value identified 532 patients (population B); with possible
      diagnosis of Chronic Obstructive Pulmonary Disease in five general practices. The
      doctors were asked to confirm the diagnosis. The same algorithm identified 2,895
      patients whom were asked to confirm their diagnosis (population C). RESULTS: In
      population A the chosen algorithm had a positive predictive value of 72.2 % and
      three criteria: a) discharged patients with a chronic lung-disease diagnosis at
      least once during the preceding 5 years; or b) redeemed prescription of lung
      medication at least twice during the preceding 12 months; or c) at least two
      spirometries performed at different dates during the preceding 12 months. In
      population B the positive predictive value was 65.0 % [60.8;69.1 %] and the
      sensitivity 44.8 % [41.3;48.4 %)] when the "uncertain" were added to where
      doctors agreed with the diagnosis. For the 1,984 respondents in population C, the
      positive predictive value was 72.9 % [70.8;74.8 %] and the sensitivity 29.7 %
      [28.4;31.0 %]. CONCLUSIONS: An algorithm based on administrative data has been
      developed and validated with sufficient positive predictive value to be used as a
      tool for identifying patients with Chronic Obstructive Pulmonary Disease. Some of
      the identified patients had other chronic lung-diseases (asthma). The algorithm
      should mostly be regarded as a tool for identifying chronic lung-disease and
      further development of the algorithm is needed. TRIAL REGISTRATION:
      www.clinicaltrials.gov (NCT01228708).

PMID- 22616578
TI  - Conductance statistics from a large array of sub-10 nm molecular junctions.
AB  - Devices made of few molecules constitute the miniaturization limit that both
      inorganic and organic-based electronics aspire to reach. However, integration of
      millions of molecular junctions with less than 100 molecules each has been a long
      technological challenge requiring well controlled nanometric electrodes. Here we
      report molecular junctions fabricated on a large array of sub-10 nm single
      crystal Au nanodots electrodes, a new approach that allows us to measure the
      conductance of up to a million of junctions in a single conducting atomic force
      microscope (C-AFM) image. We observe two peaks of conductance for alkylthiol
      molecules. Tunneling decay constant (beta) for alkanethiols, is in the same range
      as previous studies. Energy position of molecular orbitals, obtained by transient
      voltage spectroscopy, varies from peak to peak, in correlation with conductance
      values.

PMID- 22616579
TI  - Total synthesis and biological evaluation of transvalencin Z.
AB  - The emerging global epidemic of drug-resistant tuberculosis has created an urgent
      need to identify novel therapeutic approaches for disease treatment.
      Transvalencin Z (1) is a natural product from Nocardia transvalensis with
      relatively potent and selective antimycobacterial activity against Mycobacterium
      smegmatis, making it an attractive target for structure-activity and mechanism of
      action studies. The total synthesis of the four possible diastereomers of
      transvalencin Z was completed (1a-d), and the absolute configurations were
      defined using chemical synthesis, HPLC retention times, and optical rotation
      measurements. Surprisingly, none of the transvalencin Z diastereomers exhibited
      any inhibitory activity against a panel of microbial pathogens, including several
      species of mycobacteria.

PMID- 22616581
TI  - Correlation of biochemical parameters and neonatal outcome in patients with
      gestational hypertension.
AB  - Hypertensive disorders in pregnancy are one of the leading causes of maternal
      death in the world and one of the major causes of perinatal mortality. The
      incidence of hypertensive disorders in pregnancy is 8%-15%. Significant changes
      of biochemical parameters in cases of hypertensive disorders in pregnancy are
      increased levels of blood glucose, urea, creatinine, uric acid (hyperuricemia),
      transaminases, and LDH. The most increased is the level of proteinuria. Bad
      laboratory results and the intensification of clinical signs, with multiorgan
      dysfunction, are indications for termination of pregnancy.

PMID- 22616580
TI  - Sorafenib  in locally advanced or metastatic breast cancer.
AB  - INTRODUCTION: Sorafenib is an oral multikinase inhibitor with anti-angiogenic and
      anti-proliferative activity that is indicated for use in hepatocellular and renal
      cell carcinomas. Sorafenib is being developed in a number of solid tumors,
      including breast cancer (BC). AREAS COVERED: A series of four randomized, double
      blind, placebo-controlled Phase IIb screening Trials were developed to
      Investigate the Efficacy of Sorafenib (TIES) when added to select chemotherapies
      for patients with HER2-negative advanced BC with a primary endpoint of
      progression-free survival (PFS). Results have been varied. SOLTI-0701 reported
      significant PFS benefit for sorafenib plus capecitabine as first- or second-line
      treatment, and AC01B07 reported a modest but significant PFS benefit when
      sorafenib was combined with gemcitabine or capecitabine for patients whose
      disease had progressed during or after bevacizumab. Sorafenib plus first-line
      paclitaxel did not significantly improve PFS (NU07B1 study), nor did its addition
      to first-line docetaxel and/or letrozole (FM-B07-01 study). A Phase III trial of
      sorafenib plus capecitabine has been initiated. EXPERT OPINION: Phase IIb data
      indicate a potential role for sorafenib in combination with select chemotherapies
      for HER2-negative advanced BC, but Phase III confirmatory trials are necessary.
      The variability in results across studies with sorafenib may be related to the
      chemotherapy combination and/or patient population.

PMID- 22616582
TI  - The effect of melatonin on body mass and behaviour of rats during an exposure to
      microwave radiation from mobile phone.
AB  - BACKGROUND: Microwave radiation (MW) produced by wireless telecommunications and
      a number of electrical devices used in household or in healthcare institutions
      may cause various disorders in human organism. On the other hand, melatonin is a
      potent antioxidant, immunostimulator and neuromodulator. The aim of this research
      was to determine body mass and behaviour changes in rats after a chronic
      microwave exposure, as well as to determine the effects of melatonin on body mass
      and behaviour in irradiated rats. METHODS: Wistar rats were divided into the four
      experimental groups: I group (control) - rats treated with 0,9 % saline, II group
      (Mel) - rats treated with melatonin (2 mg/kg), III group (MW) - rats exposed to
      MW radiation (4 h/day), IV group (MW+Mel) - rats, which were both exposed to MW
      radiation and received melatonin premedication (2 mg/kg). RESULTS: A significant
      body mass reduction was noted in animals exposed to MW radiation when compared to
      controls after 20, 40 and 60 days (p<0.001). Furthermore, body weight was
      significantly increased (p<0.05) in irradiated rats, which received melatonin
      pretreatment (MW+Mel) in comparison to irradiated group (MW) after 20 days.
      Microwave radiation exposed animals showed an anxiety related behaviour
      (agitation, irritability) after 10 days of exposure. After the radiation source
      removal, changes in behaviour were less noticeable. Melatonin administration to
      irradiated rats caused a decrease in the stress induced behaviour. CONCLUSION:
      Microwave radiation causes body mass decrease and anxiety related behaviour in
      rats, however melatonin causes a reverse of those effects on both body weight and
      behaviour of irradiated animals (Fig. 2, Ref. 32).

PMID- 22616583
TI  - The role of nitric oxide on the responses of curcumin-treated rat aorta.
AB  - OBJECTIVES: The aim of the present study was to evaluate the influence of
      endothelial nitric oxide (NO) on the vascular responses of curcumin-treated rats.
      METHODS: The experimental groups included the control and curcumin-treated (200
      mg/kg/day, p.o., for 4 weeks) group. The concentration response curves to
      receptor-dependent agent 5-hydroxytryptamine (5-HT; 10--3x10- M) and receptor
      independent agent potassium chloride (KCl; 5-100 mM) were observed. RESULTS: The
      concentration response curves to 5-HT and KCl shifted to the right and the
      maximal response was significantly decreased in the curcumin-treated rat aortas.
      A pretreatment of rings with L-NAME (a NOS inhibitor, 10- M) increased both the
      sensitivity and maximal response to only 5-HT. No apparent histological changes
      were demonstrated in smooth muscle and connective tissue layers in the aortas of
      the control and curcumin-treated rat preparations. CONCLUSION: The results of the
      present study suggest that NO release from endothelial cells modulates curcumin
      treated rat aorta responses to 5-HT, but not to KCl (Tab. 2, Fig. 4, Ref. 25).

PMID- 22616584
TI  - The effects of ellagic acid on the liver and remote organs' oxidative stress and
      structure after hepatic ischemia reperfusion injury caused by pringle maneuver in
      rats.
AB  - INTRODUCTION: We aimed to investigate the possible protective effects of ellagic
      acid (EA) on the liver and remote organs against the hepatic ischemia-reperfusion
      injury. METHODS: Forty Wistar-Albino rats were divided into four groups each
      containing 10 rats. Group I with laparotomy only, Group II with laparatomy and
      ellagic acid application, Group III with hepatic ischemia-reperfusion and Group
      IV with hepatic ischemia-reperfusion and ellagic acid application. Hepatic
      ischemia was induced by pringle's manoeuvre for 30 minutes followed by 30 minutes
      reperfusion period. After induction of ischemia, EA was applied via oral gavage
      at a dose of 85 mg/kg. Blood samples were taken from the animals for biochemical
      analysis at 60th minute of the experiment in all groups. Simultaneously, liver,
      lung and kidney tissues were sampled for biochemical analyses and
      histopathological examinations. RESULTS: The administration of EA reduced serum
      malonyldialdehid levels (p<0.05) and liver's oxidative stress index compared with
      the non-use EA groups (p0.05). The use of EA did not exert significant protective
      effects against the effects of liver ischemia-reperfusion injury on the kidney
      and lung. CONCLUSION: In our experiments ellagic acid reduced the liver oxidative
      stress induced by ischemia-reperfusion injury. However, no significant
      histological improvement was found with EA. There were no significant protective
      effects on the remote organ injuries induced by ischemia-reperfusion (Tab. 3,
      Fig. 7, Ref. 37).

PMID- 22616585
TI  - Prevalence of mutations in thiopurine S-methyltransferase gene among Slovak IBD
      patients.
AB  - BACKGROUND: Thiopurine S-methyltransferase (TPMT) plays an important role in the
      metabolism of thiopurines. It has been suggested that TPMT genetic polymorphisms
      lead to dose-related hematopoetic toxicity. Since there are major ethnic
      differences in the prevalence of particular TPMT variants, it is important for
      each country to study their own prevalence in order to estimate the role of TPMT
      variants-related thiopurines toxicity in the particular inflammatory bowel
      disease (IBD) population. AIMS: The aim of this study was to determine the
      frequency of the four most common allelic variants of TPMT gene in the population
      of Slovak IBD patients. METHODS: TPMT genetic polymorphisms (TPMT*2, TPMT*3A,
      TPMT*3B, TPMT*3C) were amplified using PCR and consequently genotyped on genetic
      analyzer. The allele frequencies of particular allelic variants were calculated
      and compared with other Caucasian populations reported so far. RESULTS: Three
      hundred and thirty IBD patients were included; 196/132/2 Crohn's
      disease/ulcerative colitis/unclassified colitis, 180 (55 %) males. Ninety-three
      percent of patients were homozygous for wild type TPMT variant. Heterozygous
      genotype of any of the studied polymorphisms was present in 6 % of patients, only
      one patient was homozygous for TPMT*3A allele (0.3 %). The most prevalent mutant
      allele was TPMT*3A (3.2 %). The distribution of the most common allelic variants
      of TPMT gene among Slovak IBD patients were in accordance with previously
      reported prevalence in Caucasian populations. CONCLUSION: This study shows the
      prevalence of TPMT genetic polymorphisms in the Slovak IBD patient's population.
      As in other Caucasian populations, the most common mutant allelic variant is
      TPMT*3A, and the prevalence of homozygosity is relatively low (Tab. 3, Ref. 16).

PMID- 22616586
TI  - The combined algorithm of venous ulcer therapy.
AB  - AIM: This prospective study was undertaken to find a new combined algorithm to
      help patients suffering from long-term chronic non-healing venous ulcers.
      METHODS: A total number of 20 patients suffering from chronic venous ulcers and
      important co-morbidities such as diabetes mellitus or cardiac failure and not
      responding to other therapeutic modalities were treated at our surgical
      department with a combination of compressive sclerotherapy, and maggot
      debridement therapy (MDT) using larvae of green blowfly Lucilia sericata.
      RESULTS: Using the combined therapy we have achieved a significant clinical
      effect in 19 patients (95 %). In 1 patient, this effect was only impermanent
      while 5 patients (25 %) were completely cured. Eleven patients (55 %) benefited
      despite incomplete healing of the ulcer. With three of our patients we have lost
      contact. CONCLUSIONS: Even though the number of patients in our study is not
      large, we have achieved remarkable results with the combined algorithm of venous
      ulcer therapy. We start the healing process with compressive sclerotherapy and
      when this kind of therapy does not bring about the expected effect, we continue
      with Maggot debridement therapy. This combination of therapeutic modalities
      appears to be very effective and efficient (Fig. 2, Ref. 16).

PMID- 22616587
TI  - Arterio-venous fistula with pseudoaneurysm of renal artery.
AB  - INTRODUCTION: The authors describe a rare but potentially severe, sometimes even
      life-threatening complication occurring after various invasive renal
      interventions. The cause that gives rise to a fistula formation between close
      branches of renal artery and vein is an injury of these vessels during resection
      of a localised renal tumour, renal biopsy, percutaneous nephrostomy, and even
      blunt injury of the kidney. Blood flows under pressure from renal artery, pushes
      the surrounding renal parenchyma open, and creates a cavity varying in size and
      shape. This pseudoaneurysm may communicate with the collecting system of the
      kidney, in which case it may lead to haematuria, one of the typical symptoms of
      arteriovenous fistula. MATERIAL AND METHODS: The authors observed this
      complication in 8 patients (6 males aged from 56 to 70, average 61.7, and two
      females aged 28 and 54). In 7 patients, the fistula developed after resection of
      a localised renal tumour, in one patient after percutaneous nephrolitholapaxy of
      a stone in the kidney. The fistulae manifested themselves between 7 an 21 days
      after surgery by massive haematuria in 4 patients and by intermittent macroscopic
      haematuria in 3 patients. In one patient the fistula was asymptomatic while the
      pseudoaneurysm at the place of pathological connection of renal veins was found
      during ultrasonographic examination after renal resection. RESULTS: In all
      patients, the diagnosis of arteriovenous fistula and pseudoaneurysm of renal
      artery was achieved by ultrasonographic and/or CT examinations. The highest
      diagnostic value can be ascribed to digital subtraction renoangiography by
      Seldinger method that subsequently allowed active treatment by introducing an
      endovascular coil. By this method we cured 5 fistulae. In two patients, urgent
      nephrectomies were needed because of massive life-threatening haematuria. One of
      arteriovenous fistulae underwent spontaneous thrombosis. CONCLUSION: The
      symptomatic arteriovenous fistula requires fast and precise diagnosis
      subsequently enabling efficient treatment. Endovascular manipulation is a method
      allowing the preservation of kidney affected by arteriovenous fistula with renal
      artery pseudoaneurysm (Fig. 7, Ref. 21).

PMID- 22616588
TI  - Nasoalveolar molding in complete cleft lip nasal deformity patients.
AB  - OBJECTIVES: The aim of this study was to compare nostril height, width,
      collumelar length, interalar distance and nostril symetry between unilateral
      complete cleft lip/palate patients undergoing nasoalveolar moulding (NAM) and
      incomplete cleft lip patients/palate with no need of presurgical moulding before
      and after cheiloplasty with primary nasal correction. Our study group included 18
      patients from whom 9 were NAM cleft lip/palate nasal deformity cases and 9
      incomplete cleft lip/palate cases. All measurements were obtained by two
      independent investigators and averaged, standard deviations and symetry ratios
      were calculated, and paired and unpaired t-test was performed to compare the
      groups. RESULTS: Our study results showed no statistically significant difference
      in nostril height, width, collumelar lenght, interalar distance in unilateral
      cases in preoperative and postoperative measurements between these two groups.
      Symetry measurements included nostril width on the affected and nonaffected side,
      nostril height on the affected and nonaffected side before (T1) and after (T2)
      cheiloplasty. The nostril height ratio was 1.2 and 1.03 for T1 to T2 and the
      nostril width revealed a ratio of 0.5 and 0.8 for T1 to T2 in unilateral NAM
      cases. In the incomplete cleft lip group the height ratio was 1.04 and 1.03 for
      T1 to T2 and the width ratio was 0.59/0.93 in pre-/postoperative measurements.
      These symetry values showed also no statistical significance between NAM and
      incomplete cleft lip cases. CONCLUSION: Our study results showed no statistical
      significant difference in nostril height, width, collumelar lenght, interalar
      distance and nostril symetry between unilateral complete cleft lip/palate
      patients undergoing NAM and incomplete cleft lip patients/palate with no need of
      presurgical moulding, proving NAM combined with primary nasal correction is a
      very efficient management for cleft lip/palate children with outstanding results
      (Tab. 5, Fig. 4, Ref. 25). KEYWORDS: nasoalveolar molding, complete cleft lip
      nasal deformity, cleft lip, nostril height, width, collumelar lenght, interalar
      distance, nostril symetry.

PMID- 22616589
TI  - The feasibility of an early hospital discharge following chemotherapy for the
      acute myeloid leukemia.
AB  - OBJECTIVE: The hospitalization of the patient during the critical
      myelosuppressive period after chemotherapy is often complicated by infections
      caused by nosocomial pathogens, what is associated with a high antibiotics
      consumption and with prolongation of the period of hospitalization. These
      findings have led many centres to change their policy from "in-hospital" to "out
      hospital care". In this retrospective study we tried, on the basis of our
      experiences, to identify the feasibility and safety of this approach. PATIENTS
      AND METHODS: We studied 56 patients with the acute myeloid leukemia treated in
      our clinic with the consolidation chemotherapy. We compared two groups of
      patients. In the first group, the patients were discharged upon completion of
      chemotherapy, consequently followed up as outpatients. Patients in the second
      group were observed in hospital during the entire nadir. Following 41 courses,
      patients were discharged and instructed to return immediately if fever or any
      other change of their clinical status occurred. RESULTS: In 24 cases after
      chemotherapy, the patients returned to the hospital after a discharge (in 23
      cases because of fever), in 17 cases of nadir periods the hospitalisation was not
      necessary at all. Seven patients were readmitted in septic shock, but rapidly
      recovered. Two other patients died, one due to an irreversible shock within 12
      hours of readmission and one due to bacterial meningitis within 48 hours after
      readmission. In 10 cases of rehospitalization, patients responded to the first
      line of antibiotics. In the second group of the patients, only 2 courses of
      consolidation from a total of 15 were not complicated. In contrast to the first
      group, we detected only poor effectiveness of broad-spectrum antibiotics in the
      group of inpatients. CONCLUSIONS: For AML patients in a good clinical status
      without any complicating medical conditions, the early discharge is feasible,
      safe and cost saving option (Tab. 2, Fig. 2, Ref. 7).

PMID- 22616590
TI  - The role of vestibular evoked myogenic potentials (VEMPs)  in vestibulopathy
      diagnostics.
AB  - OBJECTIVE: This study presents the role of vestibular evoked myogenic potentials
      (VEMPs) in the vestibular system investigation focused on the function of the
      saccule and inferior portion of the vestibular nerve. The main goal of the study
      is to report VEMP findings in different groups of patients with inner ear
      disorders symptoms and to identify some clinical application of this test in our
      patients. MATERIAL AND METHODS: WE have examined 218 patients with
      cochleovestibular symptomatology (sudden sensorineural cochlear hearing loss,
      retrocochlear hearing loss, vestibular neuronitis, benign paroxysmal positional
      vertigo (BPPV), Meniere's disease, central vestibular disorder, as well as
      vertigo of non vestibular ethiology and 32 patients with conductive hearing loss
      with VEMP testing. We performed I channel and II channels measurements. RESULTS:
      We found no VEMP response in the group of conductive or mixed hearing loss in all
      cases - 100 % of 32 patients, in sudden sensorineural cochlear hearing loss in
      35.4 % of 48 patients, in retrocochlear hearing loss in 19 % of 26 patients, in
      vestibular neuronitis in 40 % of 35 patients , in (BPPV) in 10 % of 43 patients,
      in Meniere's disease in 61 % of 18 patients, in non vestibular vertigo in no case
      of 22 patients and in central vestibular disorders in 35 % of 23 patients.
      CONCLUSION: The present study shows the potential value of VEMP investigation in
      periferal vestibulopathy diagnosis (Tab. 1, Fig. 7, Ref. 33).

PMID- 22616592
TI  - The use of optical magnifying devices in periradicular microsurgery.
AB  - Microsurgery is a more precise modification of present procedures with less
      operative trauma and improved healing. The basic risk with traditional
      periradicular surgery arises from potential damage to major vessels or nerve
      bundles. These potential problems can be fixed using optical magnifying tools
      such as dental operating microscopes and endoscopes. Instruments have been also
      designed to take the full advantage of increased visibility. The higher
      magnification and illumination is favorable in all phases of periradicular
      surgery. The article focuses mainly on the advantages of optical magnifying
      devices by root-end resection (Tab. 1, Ref. 22).

PMID- 22616591
TI  - Molecular diagnosis of Toxoplasma gondii in pregnant women.
AB  - BACKGROUND: Novel approaches in the diagnostics of T. gondii have enabled a
      detection of the parasite in the amniotic fluid or blood of pregnant women.
      OBJECTIVE: The high titres of IgM and IgG antibodies against T. gondii are not
      always indicative of the presence of this parasite in pregnant women, therefore
      the molecular assays can be used to diagnose and genetically characterise T.
      gondii in amniotic fluids and blood samples. METHODS: The study analysed 15
      samples of amniotic fluid and 1 sample of the blood from pregnant women suspected
      for toxoplasmosis. The serological ELISA test was used for the immunological
      study and molecular analyses, PCR at SAG2 locus followed by RFLP analysis were
      used for Toxoplasma gondii genotyping. CONCLUSION: Using PCR assay with TGR1E
      gene we have confirmed the presence of T. gondii in the blood of a pregnant
      woman. The parasite was typed as genotype I, belonging to virulent strains (Tab.
      1, Fig. 2, Ref. 30).

PMID- 22616593
TI  - Moldy buildings, health of their occupants and fungal prevention.
AB  - Microscopic fungi are important biological pollutants in the indoor environment,
      they are spread generally: on building materials, carpets, ceiling tiles,
      insulations, any surfaces, wallpapers, or in heating, ventilation, and air
      conditioning systems. Molds are able to grow on any materials, as long as
      moisture and oxygen are available. Exposure to fungi in indoor environments (esp.
      in water-damaged buildings) can cause adverse health effects, such as allergy,
      asthma, hypersensitivity pneumonia, mucous membrane irritation, different toxic
      effects, or even mycoses (in immunocompromised individuals) - alone or in
      combination. As serious adverse health effects could be caused antifungal
      prevention is an absolute need.This review article summarizes the occurrence of
      fungi in the indoor environment of buildings and their contribution to occupants'
      health problems, and preventive measures against molds (Tab. 1, Fig. 1, Ref. 48).

PMID- 22616594
TI  - Hidradenitis suppurativa treated with combination of infliximab and dapsone.
AB  - Hidradenitis suppurativa (HS) is chronic inflammatory disease characterized by
      recurrent painful nodules, which leads to forming an abscess and sinus tracts,
      together with pustulation and hypertrophic scarring in the areas of apocrine
      sweat glands. Systemic and local antibiotic therapy, together with corticoid
      therapy, sulphonates, retinoids and surgical treatment with incisions and
      drainage belongs to actual treatment possibilities. Biological therapy represents
      the absolute peak in the treatment last years, mostly TNFalpha-inhibitors. Even
      though their very good short term effect is described, long term keeping up the
      good long effect of the treatment is not achieved with satisfaction. This is the
      reason to reach for traditional therapeutic possibilities combined with
      biological treatment in cases of torpid and resistive disease. In the following
      article a case report of a patient with hidradenitis suppurativa treated
      subsequently with combination of TNFalpha-inhibitors and dapson (Fig. 6, Ref.
      19).

PMID- 22616595
TI  - Integration of the e-Learning into the medical university curricula.
AB  - OBJECTIVES: The aim of this contribution was to present the e-Learning
      introduction in the Slovak Medical University (SMU) with a focus on the
      implementation phase of the two blended courses - Healthcare Quality and
      Healthcare Professionals' Ethics. BACKGROUND: The introduction of the e-Learning
      was realized during the period 2008-2009 in the partnership of SMU and IBM
      Company, following strictly the project management approach. METHODS: The
      development of the e-module beta-versions was evaluated by the modules' authors
      using a structured interview. In a consequent pilot testing, the blended courses
      were evaluated by 23 students of the bachelor program in Rescue health care, and
      by 61 public health students at the master level program, respectively, using the
      standardized questionnaires. RESULTS: The tangible results included the
      documented SMU strategy for the e-Learning integration, six e-Learning modules
      and evaluation results. The authors' evaluation showed high scores for the
      experience in collaboration with IBM, as well as for the experience with the LMS
      environment. The students' evaluation showed a high acceptance of the e-Learning
      by both part-time and full-time students. The access to Internet was not
      recognized as a serious barrier. CONCLUSION: The first experience with the
      integration of the e-Learning into the curricula of the Slovak Medical University
      showed the advantage of the systematic approach. The experience with developing
      the strategy in an interdisciplinary/ intercultural team, the knowledge about
      specific characteristics of distance learning by the involved SMU staff, and the
      know-how and skills represented the important benefits. It was demonstrated that
      the blended learning is recommended as optimal for the education in medical
      environment (Tab. 4, Fig. 1, Ref. 22).

PMID- 22616597
TI  - Signet-ring cell gastric adenocarcinoma metastasizing into a primary cutaneous
      squamous cell carcinoma of the scalp.

PMID- 22616596
TI  - Influence of kick frequency on metabolic efficiency and performance at a severe
      intensity in international monofin-swimmers.
AB  - The aim of this study was to examine the effect of kick frequency on metabolic
      efficiency and performance in elite monofin-swimmers at the surface. Seven
      participants of international calibre were requested to perform three separate
      time limit exercises conducted at an intensity corresponding to 97.5% of the
      velocity at the maximal oxygen uptake. The first Time Limit exercise was
      systematically conducted at a freely chosen kick frequency (FCK(F)) and the other
      Time Limit exercises were performed in random order at FCK(F)-10% and FCK(F) +
      10%. The slow component of oxygen uptake (VO2sc) was identified independently of
      the Time Limit exercise (ranging from 180 to 243 ml . min(-1), P < 0.05). No
      significant change in energy cost of aquatic locomotion (ranging from 565 to (596
      J . m(-1)) and [VO2sc) responses was observed between the three Time Limit
      exercises. An increase or decrease of 10% of the FCK(F) was associated with a
      significant reduction in Time Limit of -47.3% and -49.1%, respectively (P <
      0.05). The analysis of the Time Limit exercise indicates that the selection of
      kick frequency other than FCK(F) is detrimental to overall monofin-swimming
      performance. Furthermore, the study results showed that the indicators of
      metabolic efficiency such as energy cost or [VO2sc) do not determine the
      performance response in elite monofin-swimmers at a severe intensity.

PMID- 22616599
TI  - In the thick of it.

PMID- 22616600
TI  - Histopathological spectrum of cutaneous tuberculosis and non-tuberculous
      mycobacterial infections.
AB  - The non-specific clinical findings and variable histopathological features of
      cutaneous tuberculosis and non-tuberculous mycobacterial infections often make it
      difficult to establish a diagnosis and initiate appropriate therapy. We
      investigated 25 patients diagnosed with mycobacterial infections of the skin in
      Hanyang University Hospital between 2001 and 2011. Skin biopsy specimens were re
      evaluated by various histopathological criteria and molecular studies. To
      identify the mycobacteria, we performed staining for acid-fast bacilli and also
      completed polymerase chain reaction analysis. The non-tuberculous mycobacterium
      species were identified by genetic sequencing of formalin-fixed, paraffin
      embedded tissues. Immunocompromised status was more frequent in non-tuberculous
      mycobacterial infections than in tuberculosis (p = 0.017) while disease duration
      was longer in tuberculosis (p = 0.026). Microscopically, neutrophil infiltration,
      interstitial granuloma, small vessel proliferation and increased numbers of
      bacilli were found to be associated with non-tuberculous mycobacterial infections
      (all p < 0.05). In contrast, giant cells, plasma cells, tuberculoid granulomas
      and necrosis were associated with tuberculosis (all p < 0.05). There were no
      species-specific histopathological findings in non-tuberculous mycobacterial
      infections. The significant histopathological differences between cutaneous
      tuberculous and non-tuberculous mycobacterial infections are helpful in
      considering differential diagnoses. In addition, molecular techniques together
      with clinico-pathological findings may assist in making accurate diagnoses of
      cutaneous non-tuberculous mycobacterial infections.

PMID- 22616601
TI  - Histopathologic features of alopecia areata incognito: a review of 46 cases.
AB  - BACKGROUND: Alopecia areata (AA) incognito represents a variant of AA
      characterized by acute diffuse hair thinning. Dermoscopy shows yellow dots and
      short regrowing hairs. The differential diagnosis with telogen effluvium (TE) and
      androgenetic alopecia may be difficult. METHODS: In order to establish
      histopathological criteria for the diagnosis of AA incognito, we evaluated
      retrospectively 92 specimens (46 horizontal and 46 vertical) of 46 patients
      diagnosed with AA incognito within 1 year. All specimens were assessed for 20
      features, including hair counts and follicular ratios. The numbers were compared
      with 46 control specimens, consisting of 21 cases of TE and 25 cases of
      androgenetic alopecia. RESULTS: The following main criteria are proposed: (a)
      preserved number of follicular units and decreased number of terminal follicles;
      (b) increased number of telogen structures (mean count of 37%) with presence of
      at least one telogen germinal unit or/and one small telogen follicle (c)
      decreased terminal:vellus ratio (mean ratio of 3.3 : 1) and (d) dilated
      infundibular openings. CONCLUSION: Two histopathologic clues for AA incognito
      include the presence of dilated infundibular openings and small basaloid
      aggregates of cells with round, irregular or polygonal shape, lack of hair shaft
      and no apoptosis in the outer root sheath, corresponding to small telogen
      follicles.

PMID- 22616602
TI  - Proliferation and maturation of microvessels in arteriovenous malformations-
      expression patterns of angiogenic and cell cycle-dependent factors.
AB  - BACKGROUND: Areas of microvascular proliferation have been observed in a
      subpopulation of symptomatic congenital vascular malformations later in life. We
      investigated whether this angiogenic response is followed by a stage of
      maturation. METHODS: Resections of vascular malformations (n = 15), infantile
      hemangiomas (IHs) (n = 8) and pyogenic granulomas (PGs) (n = 5) were studied.
      Histopathologically, all lesions were screened for presence of foci of immature
      and/or mature microvessels. These areas were further studied
      immunohistochemically for differential expression of several angiogenic factors,
      cell cycle-dependent proteins, p53 and active caspase3. Immunostains were scored
      semiquantitatively. RESULTS: Immature microvessel areas were present in five
      vascular malformations (all of the arteriovenous type), five IHs and five PGs;
      these lesions also contained transitions between immature and mature
      microvessels. Conglomerates of mature microvessels were found in 19 cases (6
      vascular malformations, 5 PGs and 8 IHs). Expression of vascular endothelial
      growth factor-A, angiopoietin-1, Ki-67, p16 and p21/27 ratios were overall
      significantly lower in mature areas than in immature areas including those in
      vascular malformations. P53 and caspase3 expression was scarce in all lesions.
      CONCLUSIONS: Microvascular areas in vascular malformations appear to follow the
      same pattern of vascular proliferation and maturation as seen in other
      microvascular lesions of skin and soft tissue.

PMID- 22616603
TI  - Diagnosis of blue nevus-like metastatic uveal melanoma confirmed by fluorescence
      in situ hybridization (FISH) for monosomy 3.
AB  - Metastatic melanoma can on rare occasion simulate the appearance of a blue nevus
      clinically and/or histopathologically, which may lead to diagnostic confusion and
      delay in treatment. Given the known difficulty in recognizing a small dermal blue
      nevus-like melanoma metastasis by light microscopic findings alone, recent
      discoveries of unique cytogenetic aberrations in various types of melanomas have
      led pathologists to explore cytogenetic techniques as an ancillary diagnostic
      tool. Herein, we report a case of a 58-year-old man with a history of uveal
      melanoma, in which fluorescence in situ hybridization (FISH) analysis for
      monosomy 3 helped confirm a diagnosis of blue nevus-like uveal melanoma
      metastasis. The patient had presented clinically with a new small 1-mm dark blue
      gray macule on the forehead. Histopathologically, a small dermal nodule of
      pigmented epithelioid melanocytes and melanophages was found with a rare mitotic
      figure. The pathologist's suspicion of a blue nevus-like melanoma metastasis was
      confirmed by FISH analysis: both the tumor cells of the patient's prior uveal
      melanoma and the melanocytes of the new dermal blue nevus-like nodule carried
      only one copy of chromosome 3. Furthermore, deletion of 1p36 and amplifications
      of 8q32 were also identified.

PMID- 22616604
TI  - Langerhans cell sarcoma in a patient with hairy cell leukemia: common clonal
      origin indicated by identical immunoglobulin gene rearrangements.
AB  - Histiocytic/dendritic cell sarcomas are rare tumors, a few of which have been
      reported in association with B-cell lymphoma/leukemia. Isolated reports have
      documented identical immunoglobulin gene rearrangements suggesting a common
      clonal origin for both the sarcoma and the B-cell neoplasm from individual
      patients. We report a case of a 75-year-old male with hairy cell leukemia who
      subsequently developed Langerhans cell sarcoma 1 year after his primary diagnosis
      of leukemia. The bone marrow biopsy containing hairy cell leukemia and skin
      biopsies of Langerhans cell sarcoma were evaluated by routine histology,
      immunohistochemistry, flow cytometric immunophenotyping and PCR-based gene
      rearrangement studies of the immunoglobulin heavy chain and kappa genes. The
      hairy cell leukemia showed characteristic morphologic, immunohistochemical and
      flow cytometric features. The Langerhans cell sarcoma showed pleomorphic
      cytology, a high mitotic rate and characteristic immunohistochemical staining for
      Langerin, S100 and CD1a. There was no evidence of B-cell differentiation or a
      background B-cell infiltrate based on the absence of immunoreactivity with
      antibodies to multiple B-cell markers. Identical immunoglobulin gene
      rearrangements were identified in both the hairy cell leukemia and Langerhans
      cell sarcoma specimens. Despite the phenotypic dissimilarity of the two
      neoplasms, identical immunoglobulin gene rearrangements indicate a common origin.

PMID- 22616605
TI  - Follicular induction by metastatic gastric carcinoma.

PMID- 22616606
TI  - Cellular neurothekeoma with perineural extension: a potential diagnostic pitfall.

PMID- 22616608
TI  - An essential function of sphingolipids in yeast cell division.
AB  - Ceramides are bioactive lipids and precursors to sphingolipids. They have been
      shown to take part in a wide variety of different physiological processes in
      eukaryotic organisms and are thought to be toxic at high concentrations. Ceramide
      is synthesized by condensation of the sphingoid base sphinganine and a fatty acyl
      CoA by ceramide synthases, a family of enzymes that differ in their specificity
      for the length of the acyl CoA substrate. We have engineered a yeast strain where
      the endogenous ceramide synthase has been replaced by one of the putative enzymes
      from cotton. As a result, the yeast strain produces C18 rather than C26 ceramides
      showing that the cotton protein is a bona fide ceramide synthase with specificity
      towards C18 acyl CoA. Strikingly, the accumulation of C18 ceramide is not toxic
      in Saccharomyces cerevisiae. This allows survival of the yeast after deletion of
      the normally essential AUR1 (inositol phosphorylceramide synthase) gene
      permitting us to address the essential roles of sphingolipids. Deletion of AUR1
      allows cell growth, but leads to a defect in cytokinesis, which takes twice as
      long as in wild-type strains. Nuclear division and recruitment of septins is
      apparently not affected, but cytokinesis is delayed and cell separation is
      incomplete.

PMID- 22616609
TI  - Transcriptomic analysis of responses to exudates reveal genes required for
      rhizosphere competence of the endophyte Azoarcus sp. strain BH72.
AB  - Endophytic colonization is a very complex process which is not yet completely
      understood. Molecules exuded by the plants may act as signals which influence the
      ability of the microbe to colonize the host or survive in the rhizosphere. Here
      we used the whole genome microarray approach to investigate the response of the
      diazotrophic model endophyte, Azoarcus sp. strain BH72, to exudates of O. sativa
      cv. Nipponbare in order to identify differentially regulated genes. On exposure
      to exudates, an overall expression of 4.4% of the 3992 protein coding genes of
      Azoarcus sp. strain BH72 was altered, out of which 2.4% was upregulated and 2.0%
      was downregulated. Genes with modulated expression included a few whose
      involvement in plant-microbe interaction had already been established, whereas a
      large fraction comprised of genes encoding proteins with putative or unknown
      functions. Mutational analysis of several differentially regulated genes like
      those encoding a minor pilin PilX, signal transduction proteins containing GGDEF
      domains and a serine-threonine kinase as a putative component of the type IV
      secretion system (T6SS), revealed their role in host colonization. Our data
      suggest that strain BH72 may be primed for the endophytic lifestyle by exudates,
      as the expression of bacterial genes relevant for endophytic colonization of
      roots is induced by root exudates.

PMID- 22616610
TI  - Rolling the human amnion to engineer laminated vascular tissues.
AB  - The prevalence of cardiovascular disease and the limited availability of suitable
      autologous transplant vessels for coronary and peripheral bypass surgeries is a
      significant clinical problem. A great deal of progress has been made over recent
      years to develop biodegradable materials with the potential to remodel and
      regenerate vascular tissues. However, the creation of functional biological
      scaffolds capable of withstanding vascular stress within a clinically relevant
      time frame has proved to be a challenging proposition. As an alternative
      approach, we report the use of a multilaminate rolling approach using the human
      amnion to generate a tubular construct for blood vessel regeneration. The human
      amniotic membrane was decellularized by agitation in 0.03% (w/v) sodium dodecyl
      sulfate to generate an immune compliant material. The adhesion of human umbilical
      vein endothelial cells (EC) and human vascular smooth muscle cells (SMC) was
      assessed to determine initial binding and biocompatibility (monocultures).
      Extended cultures were either assessed as flat membranes, or rolled to form
      concentric multilayered conduits. Results showed positive EC adhesion and a
      progressive repopulation by SMC. Functional changes in SMC gene expression and
      the constructs' bulk mechanical properties were concomitant with vessel
      remodeling as assessed over a 40-day culture period. A significant advantage with
      this approach is the ability to rapidly produce a cell-dense construct with an
      extracellular matrix similar in architecture and composition to natural vessels.
      The capacity to control physical parameters such as vessel diameter, wall
      thickness, shape, and length are critical to match vessel compliance and tailor
      vessel specifications to distinct anatomical locations. As such, this approach
      opens new avenues in a range of tissue regenerative applications that may have a
      much wider clinical impact.

PMID- 22616611
TI  - Context-specific, scenario-based risk scales.
AB  - Reacting to an emergency requires quick decisions under stressful and dynamic
      conditions. To react effectively, responders need to know the right actions to
      take given the risks posed by the emergency. While existing research on risk
      scales focuses primarily on decision making in static environments with known
      risks, these scales may be inappropriate for conditions where the decision
      maker's time and mental resources are limited and may be infeasible if the actual
      risk probabilities are unknown. In this article, we propose a method to develop
      context-specific, scenario-based risk scales designed for emergency response
      training. Emergency scenarios are used as scale points, reducing our dependence
      on known probabilities; these are drawn from the targeted emergency context,
      reducing the mental resources required to interpret the scale. The scale is
      developed by asking trainers/trainees to rank order a range of risk scenarios and
      then aggregating these orderings using a Kemeny ranking. We propose measures to
      assess this aggregated scale's internal consistency, reliability, and validity,
      and we discuss how to use the scale effectively. We demonstrate our process by
      developing a risk scale for subsurface coal mine emergencies and test the
      reliability of the scale by repeating the process, with some methodological
      variations, several months later.

PMID- 22616612
TI  - A short history of contemporary oculoplastic surgery (and the need for RCTs):
      excerpts from the Mustarde lecture 2011.
AB  - A short review of some contemporary developments in oculoplastic surgery (OPS),
      in particular of lacimal surgery, of orbital implants and of Graves' orbitopathy,
      discloses the influence of different sorts of research and underlines (according
      to the author) the need for (more) randomized clinical trials in nowadays OPS.

PMID- 22616613
TI  - Uptake of SO2 to aqueous formaldehyde surfaces.
AB  - Aqueous surfaces act as a gateway to absorption and aqueous-phase reaction of
      gases in the atmosphere. The composition of aerosols varies greatly and is
      expected to influence the structure of the interface. For example, aldehydes
      comprise a significant fraction of atmospheric organics and are likely to
      accumulate at aqueous surfaces. But it is difficult to anticipate their effect on
      the migration of gaseous species through the interfacial region. Surface organics
      may act as a barrier to absorption, or they may facilitate uptake via cooperative
      interactions with absorbing compounds. The surface spectroscopic studies
      presented here examine the nature of the vapor/water interface during uptake of
      SO(2) to aqueous formaldehyde solutions, elucidating the role of surface species
      in a multicomponent interfacial system. The results show that the product of the
      reaction between SO(2) and formaldehyde, hydroxymethanesulfonate, shows a surface
      affinity that is enhanced in the presence of SO(2).

PMID- 22616614
TI  - Multiple anomalous systemic-pulmonary connections and coronary-pulmonary artery
      fistula associated with large aneurysms in an elderly woman.
AB  - We report the repair of a coronary artery fistula arising from the right coronary
      artery draining into the right pulmonary artery associated with multiple systemic
      pulmonary connections.

PMID- 22616615
TI  - Pathologic changes in breast cancer after anti-estrogen therapy.
AB  - Breast cancer patients do not commonly receive anti-estrogens prior to surgical
      excision. We reviewed a cohort of patients who received preoperative anti
      estrogen therapy after baseline biopsy and then had a repeat biopsy after several
      weeks on treatment. Patients with estrogen receptor positive tumors received
      anastrozole and fulvestrant in combination with gefitinib. Core needle biopsies
      were performed at day 1 and 21, and tumors were completely excised if operable at
      day 112. All patients were postmenopausal. Following treatment, tumors had
      degenerative changes including smudged nuclei, decreased nuclear size,
      intranuclear vacuoles, vacuolated cytoplasm, and increased cellular discohesion.
      In addition, increased tubule formation and intracytoplasmic lumina were seen in
      6/9 cases (66.7%) and decreased mitotic rate was demonstrated in 7/9 cases
      (77.8%). These findings indicate increased differentiation of the tumor cells in
      response to anti-estrogen therapy and that may correlate with clinical response.

PMID- 22616616
TI  - Triphenylene silanes for direct surface anchoring in binary mixed self-assembled
      monolayers.
AB  - New triphenylene-based silanes 2-(omega-(chlorodimethylsilyl)-n-alkyl)
      3,6,7,10,11-penta-m-alkoxytriphenylene 4 (Tm-Cn) with n = 8 or 9 and m = 7, 8, 9,
      10, or 11 were synthesized, and their self-assembly behavior in the liquid state
      and at glass and silicon oxide surfaces was investigated. The mesomorphic
      properties of triphenylene silanes 4 (Tm-Cn) and their precursors 3 (Tm-Cn) were
      determined by differential scanning calorimetry (DSC), polarizing optical
      microscopy (POM), and X-ray diffraction. From the small-angle X-ray scattering
      (SAXS) regime, a preferential discotic lamellar mesophase can be deduced, and
      wide-angle X-ray scattering (WAXS) highlights the liquid-like characteristics of
      the alkyl side chains. To transfer these bulk structural properties to thin
      films, self-assembled monolayers (SAMs) were obtained by adsorption from solution
      and characterized by water contact angle measurements, null ellipsometry, and
      atomic force microscopy (AFM). Employing the concentration as an additional
      degree of freedom, binary SAMs of 2-(omega-(chlorodimethylsilyl)-undecyl)
      3,6,7,10,11-penta-decyloxytriphenylene 4 (T10-C11) were coassembled with
      chlorodecyldimethylsilane or chlorodimethyloctadecylsilane, and their capability
      as model systems for organic templating was evaluated. The structure of the
      resulting binary mixed SAMs was analyzed by water contact angle measurements,
      null ellipsometry, and X-ray reflectivity (XRR) in combination with theoretical
      modeling by a multidimensional Parratt algorithm and AFM. The composition
      dependence of film thickness and roughness can be explained by a microscopic
      model including the steric hindrance of the respective molecular constituents.

PMID- 22616617
TI  - Symptomatic and functional remission in patients with first-episode psychosis.
AB  - OBJECTIVE: For patients suffering from psychotic disorders and their caregivers,
      'recovery' remains important. Our study aims to examine the rates of both
      symptomatic and functional remission in first-episode psychosis (FEP) patients at
      2 years and identify sociodemographic and clinical factors associated with
      recovery. METHOD: In this naturalistic study, all consecutive FEP patients
      presenting to an early psychosis intervention programme were recruited.
      Symptomatic remission was defined by the Schizophrenia Working Group's criteria;
      functional remission was defined as a Global Assessment of Functioning (GAF)
      disability score of >=61 with engagement in age-appropriate vocation. Simple and
      multiple logistic regressions using stepwise method were used. RESULTS: Out of
      1175 patients, 636 (54.1%) met criteria for symptomatic remission, 686 (58.4%)
      for functional remission, while 345 (29.4%) met for both. Multiple logistic
      regression revealed female gender (OR 1.47; 95%CI, 1.12-1.93), those married (OR
      1.49; 95%CI, 1.02-2.18), younger age (OR 0.98; 95%CI, 0.95-0.99), tertiary
      education (OR 1.56; 95%CI, 1.02-2.38), shorter DUP (OR 0.99; 95%CI, 0.98-0.99),
      lower baseline PANSS negative scores (OR 0.97; 95%CI, 0.95-0.99), and early
      response at month 3 (OR 1.78; 95%CI, 1.31-2.42), as significant predictors of
      recovery at year 2. CONCLUSION: Our results indicate that strategies to reduce
      DUP and achieve early response could improve remission rates in FEP patients.

PMID- 22616618
TI  - New recurrent chromosome change in pediatric therapy-related myelodysplastic
      syndrome: unbalanced translocation 1/6 with cryptic duplication of short arm of
      chromosome 6.
AB  - The incidence of therapy-related myelodysplastic syndrome (t-MDS) in pediatric
      patients is increasing in parallel with the more successful management of the
      primary tumor, but scant information is available on clinical and cytogenetic
      characteristics. We report here two children affected by t-MDS after
      chemo/radiotherapy for a primary solid tumor, both with an unbalanced
      translocation 1/6 in their bone marrow. Characterization by array comparative
      genomic hybridization of the imbalances showed an almost identical pattern:
      almost complete trisomy of the long arm of chromosome 1, and a terminal deletion
      and interstitial duplication of the short arm of chromosome 6. The gain of
      chromosome 6 short arm encompasses regions already highlighted as possibly
      relevant for t-MDS in adults, and we suggest that the unbalanced translocation
      reported here be considered a new recurrent, non-random chromosomal abnormality
      in pediatric patients with t-MDS.

PMID- 22616620
TI  - Use of an age-period-cohort model to reveal the impact of cigarette smoking on
      trends in twentieth-century adult cohort mortality in England and Wales.
AB  - We use an age-period-cohort (APC) model to estimate the contribution of smoking
      related mortality to cohort changes in adult mortality in Britain since 1950. We
      show that lung cancer and overall mortality can be satisfactorily modelled using
      cohort relative risk and a fixed age pattern. The results of the model suggest
      that smoking by itself can account for a substantial fraction of change in cohort
      mortality for those born around the first half of the twentieth century. In
      particular, smoking provides an explanation for the higher-than-average
      improvement in the mortality of both males and females born around 1930. Our
      confidence in the correctness of the results of the models is strengthened by the
      fact that they are very similar to those of the Peto-Lopez and Preston-Glei
      Wilmoth models that estimate the contribution of smoking-related to overall
      mortality.

PMID- 22616619
TI  - Willingness to share personal health record data for care improvement and public
      health: a survey of experienced personal health record users.
AB  - BACKGROUND: Data stored in personally controlled health records (PCHRs) may hold
      value for clinicians and public health entities, if patients and their families
      will share them. We sought to characterize consumer willingness and unwillingness
      (reticence) to share PCHR data across health topics, and with different
      stakeholders, to advance understanding of this issue. METHODS: Cross-sectional
      2009 Web survey of repeat PCHR users who were patients over 18 years old or
      parents of patients, to assess willingness to share their PCHR data with an-out
      of-hospital provider to support care, and the state/local public health authority
      to support monitoring; the odds of reticence to share PCHR information about ten
      exemplary health topics were estimated using a repeated measures approach.
      RESULTS: Of 261 respondents (56% response rate), more reported they would share
      all information with the state/local public health authority (63.3%) than with an
      out-of-hospital provider (54.1%) (OR 1.5, 95% CI 1.1, 1.9; p = .005); few would
      not share any information with these parties (respectively, 7.9% and 5.2%). For
      public health sharing, reticence was higher for most topics compared to
      contagious illness (ORs 4.9 to 1.4, all p-values < .05), and reflected concern
      about anonymity (47.2%), government insensitivity (41.5%), discrimination (24%).
      For provider sharing, reticence was higher for all topics compared to contagious
      illness (ORs 6.3 to 1.5, all p-values < .05), and reflected concern for relevance
      (52%), disclosure to insurance (47.6%) and/or family (20.5%). CONCLUSIONS:
      Pediatric patients and their families are often willing to share electronic
      health information to support health improvement, but remain cautious. Robust
      trust models for PCHR sharing are needed.

PMID- 22616621
TI  - Fermentative hydrogen production from glucose and starch using pure strains and
      artificial co-cultures ofClostridium spp.
AB  - BACKGROUND: Pure bacterial strains give better yields when producing H2 than
      mixed, natural communities. However the main drawback with the pure cultures is
      the need to perform the fermentations under sterile conditions. Therefore, H2
      production using artificial co-cultures, composed of well characterized strains,
      is one of the directions currently undertaken in the field of biohydrogen
      research. RESULTS: Four pure Clostridium cultures, including C. butyricum
      CWBI1009, C. pasteurianum DSM525, C. beijerinckii DSM1820 and C. felsineum
      DSM749, and three different co-cultures composed of (1) C. pasteurianum and C.
      felsineum, (2) C. butyricum and C. felsineum, (3) C. butyricum and C.
      pasteurianum, were grown in 20 L batch bioreactors. In the first part of the
      study a strategy composed of three-culture sequences was developed to determine
      the optimal pH for H2 production (sequence 1); and the H2-producing potential of
      each pure strain and co-culture, during glucose (sequence 2) and starch (sequence
      3) fermentations at the optimal pH. The best H2 yields were obtained for starch
      fermentations, and the highest yield of 2.91 mol H2/ mol hexose was reported for
      C. butyricum. By contrast, the biogas production rates were higher for glucose
      fermentations and the highest value of 1.5 L biogas/ h was observed for the co
      culture (1). In general co-cultures produced H2 at higher rates than the pure
      Clostridium cultures, without negatively affecting the H2 yields. Interestingly,
      all the Clostridium strains and co-cultures were shown to utilize lactate
      (present in a starch-containing medium), and C. beijerinckii was able to re
      consume formate producing additional H2. In the second part of the study the co
      culture (3) was used to produce H2 during 13 days of glucose fermentation in a
      sequencing batch reactor (SBR). In addition, the species dynamics, as monitored
      by qPCR (quantitative real-time PCR), showed a stable coexistence of C.
      pasteurianum and C. butyricum during this fermentation. CONCLUSIONS: The four
      pure Clostridium strains and the artificial co-cultures tested in this study were
      shown to efficiently produce H2 using glucose and starch as carbon sources. The
      artificial co-cultures produced H2 at higher rates than the pure strains, while
      the H2 yields were only slightly affected.

PMID- 22616622
TI  - Influence of the shape of crowding particles on the structural transitions in a
      polymer.
AB  - We investigate the structural transitions in a polymer induced by spherical and
      nonspherical crowding particles over a wide range of conditions. The polymer
      conformations are specified by the radius of gyration and the quality of the
      solvent in the absence of crowding particles. In the presence of crowding
      particles, the structures are altered by the volume fraction, size, shape, and
      polydispersity of the crowders. We show that crowding induces an array of
      structural changes, ranging from helix, helical hairpin (HH), and multiple helix
      bundles (HBs), depending on the interplay of multiple length and energy scales
      including the solvent quality, length of the polymer, temperature, and the
      characteristics of the crowding agents. In nearly good solvents, the polymer
      undergoes coil-helix transition in accord with the predictions based on the
      entropic stabilization mechanism. Higher-order (HH and HB) structures are
      obtained in poor or moderately poor solvents. In a binary mixture of spherical
      crowders, the effect of the two components is largely additive with the polymer
      undergoing greater compaction at higher volume fraction. In contrast to spherical
      crowders, spherocylinder-like crowders have a dramatically different effect on
      the diagram of states of the polymer. In the presence of spherocylinders, the
      polymer prefers to form a nearly ideal helix, especially at low temperatures and
      high aspect ratios of the crowders, at volume fractions that are not large enough
      for nematic order. Surprisingly, there is a complete absence of HH and HB in the
      range of conditions explored here. The dominant formation of spherocylinder
      induced helix formation is due to the tendency of the spherocylinders and the
      polymer to align along the director formed by an increase in nematic order only
      in the vicinity of the polymer. Our study, which has produced several testable
      predictions, shows that only by probing the effects of crowding on a polymer (or
      a protein and RNA) over a wide range of conditions can the diagram of states be
      quantitatively described.

PMID- 22616624
TI  - Diversin, from Ferula diversivittata protects human lymphocytes against oxidative
      stress induced by H2O2.
AB  - In this study, the antigenotoxic effects of diversin, a prenylated coumarin
      obtained from Ferula diversivittata roots were evaluated using comet assay.
      Isolated lymphocytes from healthy volunteers' blood samples were incubated with
      diversin (10, 25, 50, 100, 200 and 400 uM) alone, or in the presence of H2O2 (25
      uM). DNA break was measured based on the %tail DNA and compared with different
      concentrations of curcumin (10, 25 and 50 uM) as the positive control. It was
      shown that all concentrations of diversin significantly reduce DNA damage caused
      by H2O2.

PMID- 22616623
TI  - Development of iron-doped silicon nanoparticles as bimodal imaging agents.
AB  - We demonstrate the synthesis of water-soluble allylamine-terminated Fe-doped Si
      (Si(xFe)) nanoparticles as bimodal agents for optical and magnetic imaging. The
      preparation involves the synthesis of a single-source iron-containing precursor,
      Na(4)Si(4) with x% Fe (x = 1, 5, 10), and its subsequent reaction with NH(4)Br to
      produce hydrogen-terminated Si(xFe) nanoparticles. The hydrogen-capped
      nanoparticles are further terminated with allylamine via thermal hydrosilylation.
      Transmission electron microscopy indicates that the average particle diameter is
      ~3.0 +/- 1.0 nm. The Si(5Fe) nanoparticles show strong photoluminescence quantum
      yield in water (~10%) with significant T(2) contrast (r(2)/r(1) value of 4.31).
      Electron paramagnetic resonance and Mossbauer spectroscopies indicate that iron
      in the nanoparticles is in the +3 oxidation state. Analysis of cytotoxicity using
      the resazurin assay on HepG2 liver cells indicates that the particles have
      minimal toxicity.

PMID- 22616625
TI  - Taxonomic and symbiotic diversity of bacteria isolated from nodules of  Acacia
      tortilis  subsp. raddiana in arid soils of Tunisia.
AB  - A collection of rhizobia isolated from Acacia tortilis subsp. raddiana nodules
      from various arid soils in Tunisia was analyzed for their diversity at both
      taxonomic and symbiotic levels. The isolates were found to be phenotypically
      diverse. The majority of the isolates tolerated 3% NaCl and grew at 40  degrees
      C. Genetic characterization emphasized that most of the strains (42/50) belong to
      the genus Ensifer, particularly the species Ensifer meliloti, Ensifer
      garamanticus, and Ensifer numidicus. Symbiotic properties of isolates showed
      diversity in their capacity to nodulate their host plant and to fix atmospheric
      nitrogen. The most effective isolates were closely related to E. garamanticus.
      Nodulation tests showed that 3 strains belonging to Mesorhizobium genus failed to
      renodulate their host plant, which is surprising for symbiotic rhizobia.
      Furthermore, our results support the presence of non-nodulating endophytic
      bacteria belonging to the Acinetobacter genus in legume nodules.

PMID- 22616626
TI  - TMC435  for the treatment of chronic hepatitis C.
AB  - INTRODUCTION: Chronic hepatitis C (CHC) virus infection affects more than 170
      million people globally. The aim of treatment of CHC is to effect sustained
      elimination of the virus (a sustained virological response, SVR). Prior to the
      development of direct-acting antiviral (DAA) agents, the standard of care (SOC)
      for CHC comprised combined treatment with pegylated interferon (PegIFN) and
      ribavirin (RBV). AREAS COVERED: TMC435 (Tibotec pharmaceuticals) is a macrocyclic
      non-covalent NS3/NS4A protease inhibitor (DAA) that is currently in Phase III
      clinical development. TMC435 is being developed in treatment regimens both with
      and without PegIFN and RBV. In Phase IIb clinical trials, the addition of TMC435
      to current SOC significantly increased the SVR rate in both treatment-naive and
      experienced patients with CHC. It differs, however, from the other first
      generation protease inhibitors in that it is administered once daily, has a
      different tolerability and resistance profile and has activity against CHC
      genotypes 1 - 6 with the exception of genotype 3. Furthermore, the addition of
      TMC435 to PegIFN/RBV appears to be able to significantly shorten treatment
      duration in the majority of patients. This article will review the pharmacology,
      pharmacodynamics, safety and efficacy of TMC435 by evaluating the preclinical and
      clinical studies to date. EXPERT OPINION: TMC435 is a 'second-wave' protease
      inhibitor that has the potential to play a pivotal role in the next phase of CHC
      treatment. The forthcoming results of Phase III trials involving TMC435 are
      awaited with interest.

PMID- 22616627
TI  - Prostate cancer incidence and mortality in rural men--a systematic review of the
      literature.
AB  - INTRODUCTION: Prostate cancer is a common health problem in men worldwide. This
      systematic review has been undertaken to determine if there are differences in
      incidence of and mortality from prostate cancer between rural and urban men. The
      understanding of geographical patterns of prostate cancer incidence and mortality
      is necessary in order to identify and assess any disparities between rural and
      urban residents in gaining access to healthcare services, such as screening,
      diagnosis and treatment. METHODS: Medline, CINAHL and Embase were searched using
      relevant mesh phrases, such as 'prostate cancer incidence rural' or 'prostatic
      neoplasms mortality rural'. Secondary literature and reports not published in
      peer-reviewed journals were included if inclusion criteria had been met. The
      following inclusion criteria were applied: cohort (population-based study) of
      adult men, diagnosis of prostate cancer, comparing rural and urban groups, and
      incidence or mortality with available statistical parameters as outcome. RESULTS:
      In total, 25 studies were found to fit the inclusion criteria. Sixteen cohort
      studies were identified that examined incidence of prostate cancer in rural and
      urban populations, while 18 studies focused on mortality. Nine of these
      publications discussed both aspects. Twenty of these studies were published in
      scientific journals, while five were reports identified through secondary
      literature search. Prostate cancer incidence was found to be higher in urban men,
      while mortality patterns seemed to vary to some degree depending on different
      definitions of rural/urban groups, as well as on variations in demographic
      factors and study periods. There is evidence, however, that after prostate
      specific antigen testing was introduced death rates tended to be higher in rural
      men with prostate cancer. CONCLUSIONS: The review of the literature showed that
      in spite of inconsistent definitions of rural/urban categories among studies the
      majority reported higher incidence rates in urban men. This finding suggests that
      rural men are less likely to be screened and less likely to be subsequently
      diagnosed with prostate cancer. Although mortality patterns tended to be
      heterogeneous, there was some evidence that rural residents with prostate cancer
      experience higher death rates. It would be beneficial if future studies take into
      consideration factors such as stage at initial diagnosis, ethnicity, and
      socioeconomic and health status when assessing differences in cancer outcomes.
      Few studies in this review accounted for one or more of these variables, although
      there are indications that they contribute to differences in prostate cancer
      incidence and mortality between rural and urban populations.

PMID- 22616628
TI  - A phase 1, randomized, placebo-controlled, dose-escalation study of an anti-IL-13
      monoclonal antibody in healthy subjects and mild asthmatics.
AB  - AIMS: IL-13 is implicated as an important mediator of the pathology of asthma.
      This first clinical study with GSK679586, a novel humanized anti-IL-13 IgG1
      monoclonal antibody, evaluated the safety, pharmacokinetics and pharmacodynamics
      of escalating single and repeat doses of GSK679586. METHODS: In this randomized,
      double-blind study, healthy subjects received single intravenous infusions of
      GSK679586 (0.005, 0.05, 0.5, 2.5, 10 mg kg(-1)) or placebo and mild intermittent
      asthmatics received two once monthly intravenous infusions of GSK679586 (2.5, 10,
      20 mg kg(-1)) or placebo. RESULTS: GSK679586 displayed approximately linear
      pharmacokinetics (based on AUC and C(max)) with limited accumulation upon repeat
      administration. In mild intermittent asthmatics, treatment with GSK679586
      produced an increase in serum total IL-13 concentrations, indicative of GSK679586
      IL-13 complex formation. Additionally, mean levels of exhaled nitric oxide
      (FeNO), a marker of pulmonary inflammation, were reduced relative to baseline at
      2.5, 10 and 20 mg kg(-1) doses of GSK679586 at both 2 weeks (19%, 44% and 52%
      decreases) and 8 weeks (29%, 55% and 42% decreases) after the second infusion.
      GSK679586 was well tolerated; the incidence of AEs was comparable across all
      presumed biologically active doses and there were no treatment-related SAEs.
      CONCLUSIONS: GSK679586 demonstrated dose-dependent pharmacological activity in
      the lungs of mild intermittent asthmatics. These findings, together with the
      favourable safety profile and advantageous PK characteristics of a monoclonal
      antibody (e.g. a long half-life supporting less frequent dosing), warrant further
      investigation of GSK679586 in a broader asthma patient population.

PMID- 22616629
TI  - The return period analysis of natural disasters with statistical modeling of
      bivariate joint probability distribution.
AB  - New features of natural disasters have been observed over the last several years.
      The factors that influence the disasters' formation mechanisms, regularity of
      occurrence and main characteristics have been revealed to be more complicated and
      diverse in nature than previously thought. As the uncertainty involved increases,
      the variables need to be examined further. This article discusses the importance
      and the shortage of multivariate analysis of natural disasters and presents a
      method to estimate the joint probability of the return periods and perform a risk
      analysis. Severe dust storms from 1990 to 2008 in Inner Mongolia were used as a
      case study to test this new methodology, as they are normal and recurring
      climatic phenomena on Earth. Based on the 79 investigated events and according to
      the dust storm definition with bivariate, the joint probability distribution of
      severe dust storms was established using the observed data of maximum wind speed
      and duration. The joint return periods of severe dust storms were calculated, and
      the relevant risk was analyzed according to the joint probability. The copula
      function is able to simulate severe dust storm disasters accurately. The joint
      return periods generated are closer to those observed in reality than the
      univariate return periods and thus have more value in severe dust storm disaster
      mitigation, strategy making, program design, and improvement of risk management.
      This research may prove useful in risk-based decision making. The exploration of
      multivariate analysis methods can also lay the foundation for further
      applications in natural disaster risk analysis.

PMID- 22616631
TI  - Enantioselective alpha-vinylation of aldehydes via the synergistic combination of
      copper and amine catalysis.
AB  - The enantioselective alpha-vinylation of aldehydes using vinyl iodonium triflate
      salts has been accomplished via the synergistic combination of copper and chiral
      amine catalysis. These mild catalytic conditions provide a direct route for the
      enantioselective construction of enolizable alpha-formyl vinylic stereocenters
      without racemization or olefin transposition. These high-value coupling adducts
      are readily converted into a variety of useful olefin synthons.

PMID- 22616632
TI  - Fragmented esophageal smooth muscle contraction segments on high resolution
      manometry: a marker of esophageal hypomotility.
AB  - BACKGROUND: Esophageal peristalsis consists of a chain of contracting striated
      and smooth muscle segments on high resolution manometry (HRM). We compared smooth
      muscle contraction segments in symptomatic subjects with reflux disease to
      healthy controls. METHODS: High resolution manometry Clouse plots were analyzed
      in 110 subjects with reflux disease (50 +/- 1.4 years, 51.5% women) and 15
      controls (27 +/- 2.1 years, 60.0% women). Using the 30 mmHg isobaric contour
      tool, sequences were designated fragmented if either smooth muscle contraction
      segment was absent or if the two smooth muscle segments were separated by a
      pressure trough, and failed if both smooth muscle contraction segments were
      absent. The discriminative value of contraction segment analysis was assessed.
      KEY RESULTS: A total of 1115 swallows were analyzed (reflux group: 965, controls:
      150). Reflux subjects had lower peak and averaged contraction amplitudes compared
      with controls (P < 0.0001 for all comparisons). Fragmented sequences followed
      18.4% wet swallows in the reflux group, compared with 7.5% in controls (P <
      0.0001), and were seen more frequently than failed sequences (7.9% and 2.5%,
      respectively). Using a threshold of 30% in individual subjects, a composite of
      failed and/or fragmented sequences was effective in segregating reflux subjects
      from control subjects (P = 0.04). CONCLUSIONS & INFERENCES: Evaluation of smooth
      muscle contraction segments adds value to HRM analysis. Specifically, fragmented
      smooth muscle contraction segments may be a marker of esophageal hypomotility.

PMID- 22616633
TI  - Marine sulfate-reducing bacteria cause serious corrosion of iron under
      electroconductive biogenic mineral crust.
AB  - Iron (Fe(0) ) corrosion in anoxic environments (e.g. inside pipelines), a process
      entailing considerable economic costs, is largely influenced by microorganisms,
      in particular sulfate-reducing bacteria (SRB). The process is characterized by
      formation of black crusts and metal pitting. The mechanism is usually explained
      by the corrosiveness of formed H(2) S, and scavenge of 'cathodic' H(2)  from
      chemical reaction of Fe(0)  with H(2) O. Here we studied peculiar marine SRB that
      grew lithotrophically with metallic iron as the only electron donor. They
      degraded up to 72% of iron coupons (10 mm * 10 mm * 1 mm) within five months,
      which is a technologically highly relevant corrosion rate (0.7 mm Fe(0)  year(-1)
      ), while conventional H(2) -scavenging control strains were not corrosive. The
      black, hard mineral crust (FeS, FeCO(3) , Mg/CaCO(3) ) deposited on the corroding
      metal exhibited electrical conductivity (50 S m(-1) ). This was sufficient to
      explain the corrosion rate by electron flow from the metal (4Fe(0)  -> 4Fe(2+)  +
      8e(-) ) through semiconductive sulfides to the crust-colonizing cells reducing
      sulfate (8e(-)  + SO(4) (2-)  + 9H(+)  -> HS(-)  + 4H(2) O). Hence, anaerobic
      microbial iron corrosion obviously bypasses H(2)  rather than depends on it. SRB
      with such corrosive potential were revealed at naturally high numbers at a
      coastal marine sediment site. Iron coupons buried there were corroded and covered
      by the characteristic mineral crust. It is speculated that anaerobic biocorrosion
      is due to the promiscuous use of an ecophysiologically relevant catabolic trait
      for uptake of external electrons from abiotic or biotic sources in sediments.

PMID- 22616634
TI  - Epithelioid sarcoma of the penis: a case report.
AB  - INTRODUCTION: Epithelioid sarcoma of the penis is a slowly growing soft tissue
      neoplasm that rarely arises from the penis. AIM: The aim of this case is to
      describe this rare pathology and to underline the importance of differential
      diagnosis with benign diseases such as Peyronie's disease. METHOD: We report the
      case of a 20-year-old man who referred the onset of a progressive left
      dorsolateral penile curvature (about 60 degrees ) started 3 years before. The
      patient was evaluated with two US examinations that revealed two sites of tunical
      thickening with normal hemodynamic evaluation. The physical examination
      demonstrated a dorsal fibrotic plaque of about 2.5 cm. RESULTS: A juvenile form
      of Peyronie's Disease was diagnosed, and the patient was scheduled for surgical
      treatment (plaque's incision/excision and grafting). Intraoperative appearance
      showed that the great part of the left cavernous body was substituted by a very
      tough tissue which deeply involved the erectile tissue; intraoperative frozen
      section was suspicious for mesenchymal epithelioid neoplasm. In order to obtain
      definitive histological analysis and collect proper informed consent, we
      preferred to proceed with our original project, applying a dual graft (buccal
      mucosa and allograft dermal matrix) to cover the wide excised area. The final
      histological report confirmed the diagnosis of epithelioid sarcoma. Postoperative
      CT and MRI, at 3 and 6 months from surgery, were negative for metastases. The
      patient underwent radical intervention after 6 months. CONCLUSIONS: Epithelioid
      sarcoma of the penis and Peyronie's Disease can present with similar clinical
      findings although they obviously entail a different clinical progress. Since the
      diagnosis of neoplasm can be established only by the pathologist on biopsy
      specimen, in cases of unusual clinical presentation of Peyronie's disease
      (especially in young men suffering from a fast-growing penile induration), an
      early histological assessment should be performed to avoid the possibility of
      misdiagnosis in case of this poor-prognosis disease and to assure the definitive
      diagnosis.

PMID- 22616635
TI  - Quality of life and satisfaction with life of malaria patients in context of
      acceptance of the disease: quantitative studies.
AB  - BACKGROUND: Health status is one of the basic factors of a high quality of life
      and the problem of the acceptance of illness is important for adaptation to the
      limitations imposed by it. The purpose of the study was the evaluation of the
      quality of life, satisfaction with life and the acceptance of illness by malaria
      patients, as well as the discovery of a relationship between studied parameters.
      METHODS: The study was undertaken in August 2010, on 120 Nigerian patients with
      confirmed malaria. A method of diagnostic survey, based on standardized scales -
      Acceptance of Illness Scale, The Satisfaction With Life Scale and a standardized
      survey questionnaire World Health Organization Quality of Life/BREF - was used in
      this study. Descriptive statistics, variability range, 95% confidence interval,
      correlation analysis, Spearman's non-parametric correlation coefficient, Mann
      Whitney test and Kruskal-Wallis test were applied and the, so called, test
      statistics was calculated, followed by the calculation of the test probability p.
      Results of analyses were presented in a box graph, and a graph of dispersion.
      RESULTS: A dominating share in the adjective scale of the AIS scale was the
      category of "no acceptance", given by 71.7% of respondents. The average level of
      a "somatic domain" was 41.7, and of a "social domain" was 62.8. The mean
      satisfaction of life evaluation in the SWLS scale was 18 points. The correlation
      between acceptance of the disease and quality of life for the psychological
      domain was 0.39***, and between acceptance of the disease and satisfaction with
      life was 0.40***. The correlation between satisfaction with life and quality of
      life for the psychological domain was 0.65***, and between satisfaction with life
      and quality of life for the environment domain was 0.60***. The mean level of AIS
      for the studied population of men was 16.5, and test probability: p = 0.0014**,
      and for the environment domain the level was 50, and the test probability: p =
      0.0073**. For quality of life in the social sphere the test probability: p =
      0.0013** in relatively older individuals. CONCLUSION: The majority of people do
      not accept their condition. Evaluation of the quality of life was the highest in
      the social domain, and the lowest in the somatic domain. There is a statistically
      significant correlation between the level of acceptance of illness and the
      quality of life and satisfaction with life. The strongest correlation is found
      between satisfaction with life and the evaluation of the quality of life in
      psychological and environmental domains. Men evaluate their quality of life in
      the environmental domain higher and demonstrate a higher acceptance of their
      disease. There is a correlation regarding a significantly higher quality of life
      in the social sphere in relatively older people.

PMID- 22616636
TI  - Contributing variables to post mastectomy tissue expander infection.
AB  - Tissue expander breast reconstruction is a common post mastectomy breast
      procedure performed by plastic surgeons. The purpose of this study was to define
      the incidence of breast reconstruction prosthetic infection, relate patient
      characteristics with increased rate of infection, and analyze the influence of
      postoperative complications to expander/implant infection. A retrospective,
      single-institution chart review of 195 women with post mastectomy tissue
      expander/implant reconstructions performed from 2006 through 2008 was conducted.
      Total periprosthetic infection rate was calculated. Patient factors, operative
      technique, and noninfectious complications were analyzed and related to increased
      periprosthetic infection rate. A binary logistic regression model was fitted
      using periprosthetic infection as the dependent variable and 12 patient
      characteristics as independent variables, followed by a step-wise model for best
      fit with a limited number of independent variables. The overall periprosthetic
      infection rate per patient over the 2 year period was 5.1%. The incidence of
      periprosthetic infection per reconstructed breast was 3.2%. Odds ratio estimates
      indicated that the presence of cellulitis increased the odds of periprosthetic
      infection more than 200 times (p = <0.0001), and inpatient procedures increased
      the odds 16 times (p = 0.02). Other variables (i.e., age > 65, DM, flap necrosis,
      smoking, dehiscence, AlloDerm, etc) failed to reach statistical significance (p >
      0.05). Postoperative breast cellulitis and inpatient status appear to be
      significant risk factors for increased periprosthetic infection. No significant
      increase in periprosthetic infection rate was noted with other variables in this
      model.

PMID- 22616638
TI  - Exercise increases the frequency of circulating hematopoietic progenitor cells,
      but reduces hematopoietic colony-forming capacity.
AB  - Circulating hematopoietic progenitor cells (CPCs) may be triggered by physical
      exercise and/or normobaric hypoxia from the bone marrow. The aim of the study was
      to investigate the influence of physical exercise and normobaric hypoxia on CPC
      number and functionality in the peripheral blood as well as the involvement of
      oxidative stress parameters as possibly active agents. Ten healthy male subjects
      (25.3+/-4.4 years) underwent a standardized cycle incremental exercise test
      protocol (40 W+20 W/min) under either normoxic (FiO2 ~0.21) or hypoxic conditions
      (FiO2<0.15, equals 3,500 m, 3 h xposure) within a time span of at least 1 week.
      Blood was drawn from the cubital vein before and 10, 30, 60, and 120 min after
      exercise. The number of CPCs in the peripheral blood was analyzed by flow
      cytometry (CD34/CD45-positive cells). The functionality of cells present was
      addressed by secondary colony-forming unit-granulocyte macrophage (CFU-GM)
      assays. To determine a possible correlation between the mobilization of CPCs and
      reactive oxygen species, parameters for oxidative stress such as malondialdehyde
      (MDA) and myeloperoxidase (MPO) were obtained. Data showed a significant increase
      of CPC release under normoxic as well as hypoxic conditions after 10 min of
      recovery (P<0.01). Most interestingly, although CD34+/CD45dim cells increased in
      number, the proliferative capacity of CPCs decreased significantly 10 min after
      cessation of exercise (P<0.05). A positive correlation between CPCs and MDA/MPO
      levels turned out to be significant for both normoxic and hypoxic conditions
      (P<0.05/P<0.01). Hypoxia did not provoke an additional effect. Although the CPC
      frequency increased, the functionality of CPCs decreased significantly after
      exercise, possibly due to the influence of increased oxidative stress levels.

PMID- 22616637
TI  - Structural evolution of environmentally responsive cationic liposome-DNA
      complexes with a reducible lipid linker.
AB  - Environmentally responsive materials (i.e., materials that respond to changes in
      their environment with a change in their properties or structure) are attracting
      increasing amounts of interest. We recently designed and synthesized a series of
      cleavable multivalent lipids (CMVLn, with n = 2-5 being the number of positive
      headgroup charges at full protonation) with a disulfide bond in the linker
      between their cationic headgroup and hydrophobic tails. The self-assembled
      complexes of the CMVLs and DNA are a prototypical environmentally responsive
      material, undergoing extensive structural rearrangement when exposed to reducing
      agents. We investigated the structural evolution of CMVL-DNA complexes at varied
      complex composition, temperature, and incubation time using small-angle X-ray
      scattering (SAXS) and wide-angle X-ray scattering (WAXS). A related lipid with a
      stable linker, TMVL4, was used as a control. In a nonreducing environment, CMVL
      DNA complexes form the lamellar (L(alpha)(C)) phase, with DNA rods sandwiched
      between lipid bilayers. However, new self-assembled phases form when the
      disulfide linker is cleaved by dithiothreitol or the biologically relevant
      reducing agent glutathione. The released DNA and cleaved CMVL headgroups form a
      loosely organized phase, giving rise to a characteristic broad SAXS correlation
      profile. CMVLs with high headgroup charge also form condensed DNA bundles.
      Intriguingly, the cleaved hydrophobic tails of the CMVLs reassemble into tilted
      chain-ordered L(beta') phases upon incubation at physiological temperature (37 
      degrees C), as indicated by characteristic WAXS peaks. X-ray scattering further
      reveals that two of the three phases (L(betaF), L(betaL), and L(betaI))
      constituting the L(beta') phase coexist in these samples. The described system
      may have applications in lipid-based nanotechnologies.

PMID- 22616639
TI  - Late left ventricular perforation by active fixation pacemaker lead implanted in
      the right ventricular septum.
AB  - We report a rare case of late left ventricular perforation caused by a migrated
      pacemaker lead, which had been implanted in the right ventricular septum three
      months prior. Preoperative computed tomography findings revealed that the tip of
      the migrated pacemaker lead had perforated the ventricular wall near the
      intraventricular groove into the anterior chest wall.

PMID- 22616640
TI  - Primary care physicians' and psychiatrists' approaches to treating mild
      depression.
AB  - OBJECTIVE: To measure how primary care physicians (PCPs) and psychiatrists treat
      mild depression. METHOD: We surveyed a national sample of US PCPs and
      psychiatrists using a vignette of a 52-year-old man with depressive symptoms not
      meeting Major Depressive Episode criteria. Physicians were asked how likely they
      were to recommend an antidepressant counseling, combined medication, and
      counseling or to make a psychiatric referral. RESULTS: Response rate was 896/1427
      PCPs and 312/487 for psychiatrists. Compared with PCPs, psychiatrists were more
      likely to recommend an antidepressant (70% vs. 56%), counseling (86% vs. 54%), or
      the combination of medication and counseling (61% vs. 30%). More psychiatrists
      (44%) than PCPs (15%) were 'very likely' to promote psychiatric referral. PCPs
      who frequently attended religious services were less likely (than infrequent
      attenders) to refer the patient to a psychiatrist (12% vs. 18%); and more likely
      to recommend increased involvement in meaningful relationships/activities (50%
      vs. 41%) and religious community (33% vs. 17%). CONCLUSION: Psychiatrists treat
      mild depression more aggressively than PCPs. Both are inclined to use
      antidepressants for patients with mild depression.

PMID- 22616641
TI  - Improved elevated temperature performance of Al-intercalated V(2)O(5) electrospun
      nanofibers for lithium-ion batteries.
AB  - Al-inserted vanadium pentoxide (V2O5) nanofibers (Al-VNF) are synthesized by
      simple electrospinning technique. Powder X-ray diffraction (XRD) patterns confirm
      the formation of phase-pure structure. Elemental mapping and XPS studies are used
      to confirm chemical insertion of Al in VNF. Surface morphological features of as
      spun and sintered fibers with Al-insertion are investigated by field-emission
      scanning electron microscopy (FE-SEM). Electrochemical Li-insertion behavior of
      Al-VNFs are explored as cathode in half-cell configuration (vs. Li) using cyclic
      voltammetry and galvanostatic charge-discharge studies. Al-VNF (Al0.5V2O5) shows
      an initial discharge capacity of ~250 mA h g(-1) and improved capacity retention
      of >60% after 50 cycles at 0.1 C rate, whereas native VNF showed only ~40%
      capacity retention at room temperature. Enhanced high current rate and elevated
      temperature performance of Al-VNF (Al1.0V2O5) is observed with improved capacity
      retention (~70%) characteristics. Improved performance of Al-inserted VNF is
      mainly attributed to the retention of fibrous morphology, apart from structural
      stabilization during electrochemical cycling. 

PMID- 22616642
TI  - Off-target effects of BCR-ABL1 inhibitors and their potential long-term
      implications in patients with chronic myeloid leukemia.
AB  - In patients with chronic myeloid leukemia (CML), use of the BCR-ABL1-specific
      tyrosine kinase inhibitors (TKIs) imatinib, nilotinib and dasatinib has greatly
      improved patient survival and prolonged disease remission. More than 10 years of
      data from imatinib clinical studies and many years of data for nilotinib and
      dasatinib have demonstrated that these TKIs are well tolerated in most patients
      with CML. However, these inhibitors are not entirely BCR-ABL1-specific, and this
      lack of specificity could account for the off-target effects of these drugs.
      Adverse events (AEs) are off-target effects that are detrimental to the patient.
      The underlying mechanisms that contribute to these effects are poorly understood
      and the long-term consequences of chronic TKI therapy remain largely unknown,
      particularly with the newer agents. Here, we review the preclinical and clinical
      data for several of the more frequent AEs associated with TKIs and discuss the
      therapeutic relevance of these AEs for patients with CML.

PMID- 22616643
TI  - Eyelid lipomas: a case report and review of the literature.
AB  - Simple lipomas of the eyelid are rare. We present a case of a 61-year-old man,
      who presented with 6 months of a slowly worsening blepharoptosis. On examination,
      that patient was noted to have a palpable, soft mass in the medial left upper
      eyelid. Histopathological examination of the mass revealed mature adipose tissue
      most consistent with lipoma. Simple lipomas of the eyelid are very unusual but
      should be considered in the differential diagnosis of patients presenting with
      mechanical ptosis.

PMID- 22616644
TI  - Aggregation control of quantum dots through ion-mediated hydrogen bonding
      shielding.
AB  - Nanoparticle stabilization against detrimental aggregation is a critical
      parameter that needs to be well controlled. Herein, we present a facile and rapid
      ion-mediated dispersing technique that leads to hydrophilic aggregate-free
      quantum dots (QDs). Because of the shielding of the hydrogen bonds between
      cysteamine-capped QDs, the presence of F(-) ions disassembled the aggregates of
      QDs and afforded their high colloidal stability. The F(-) ions also greatly
      eliminated the nonspecific adsorption of the QDs on glass slides and cells.
      Unlike the conventional colloidal stabilized method that requires the use of any
      organic ligand and/or polymer for the passivation of the nanoparticle surface,
      the proposed approach adopts the small size and large diffusion coefficient of
      inorganic ions as dispersant, which offers the disaggregation a fast reaction
      dynamics and negligible influence on their intrinsic surface functional
      properties. Therefore, the ion-mediated dispersing strategy showed great
      potential in chemosensing and biomedical applications.

PMID- 22616646
TI  - The role of high-dose corticosteroids in the treatment of chronic lymphocytic
      leukemia.
AB  - INTRODUCTION: Management of refractory chronic lymphocytic leukemia (CLL)
      represents a major challenge because of the poor prognosis and limited treatment
      options. While corticosteroids have been used to treat CLL since 1940s, their
      benefit has never been conclusively proved. Recently, several groups reported use
      of high-dose corticosteroids (methylprednisolone or dexamethasone) either alone
      or combined with chemotherapy and/or monoclonal antibodies in relapsed/refractory
      CLL. AREAS COVERED: While efficacy of high-dose corticosteroids is excellent
      including responses in patients with bulky lymphadenopathy or those considered
      ultra high-risk CLL because of deletion and/or mutation of p53 gene, the duration
      of response is still unsatisfactory. Combination with monoclonal antibodies seems
      to improve therapeutic efficacy but no randomized trials have been conducted. For
      the purpose of this review, a search for terms, high-dose
      corticosteroids/methylprednisolone/dexamethasone, and chronic lymphocytic
      leukemia has been performed in PubMed and database of abstracts from American
      Society of Hematology Meetings. EXPERT OPINION: High-dose corticosteroids appear
      to play an important role in the management of highly pretreated
      relapsed/refractory CLL including patients with massive lymphadenopathy.
      Myelosuppression is usually limited but infectious toxicity, including increased
      risk of invasive fungal infections, represents the most dreaded side effects.
      This therapeutic approach should be further tested within large prospective
      trials, to optimize efficacy and safety.

PMID- 22616645
TI  - Food Intake Recording Software System, version 4 (FIRSSt4): a self-completed 24-h
      dietary recall for children.
AB  - The Food Intake Recording Software System, version 4 (firsst4), is a web-based 24
      h dietary recall (24 hdr) self-administered by children based on the Automated
      Self-Administered 24-h recall (ASA24) (a self-administered 24 hdr for adults).
      The food choices in firsst4 are abbreviated to include only those reported by
      children in US national surveys; and detailed food probe questions are simplified
      to exclude those that children could not be expected to answer (e.g. questions
      regarding food preparation and added fats). ASA24 and firsst4 incorporate 10 000+
      food images, with up to eight images per food, to assist in portion size
      estimation. We review the formative research conducted during the development of
      firsst4. When completed, firsst4 will be hosted and maintained for investigator
      use on the National Cancer Institute's ASA24 website. 

PMID- 22616647
TI  - Low drug resistance levels among drug-naive individuals with recent HIV type 1
      infection in a rural clinical cohort in southwestern Uganda.
AB  - To investigate the prevalence of transmitted drug resistance (TDR) among
      individuals with recent HIV-1 infection between February 2004 and January 2010 in
      a rural clinical cohort, samples from 72 participants were analyzed. Results from
      the 72 participants showed no protease inhibitor and nucleoside reverse
      transcriptase inhibitor-associated mutations. One participant (1.4%, 95% CI: 0.04
      7.5%) had two nonnucleoside reverse transcriptase inhibitor mutations (G190E and
      P225H). HIV-1 subtype frequencies were A 22 (30.6%), D 38 (52.8%), and C 1
      (1.4%); 11 (15.3%) were A/D unique recombinant forms. Seven years after the scale
      up of antiretroviral therapy (ART) in a rural clinical cohort in Uganda, the
      prevalence of TDR among recently HIV-1-infected individuals was low at 1.4%.
      Since our findings from an HIV study cohort may not be generalizable to the
      general population, routine TDR surveys in specific populations may be necessary
      to inform policy on the magnitude and prevention strategies of TDR.

PMID- 22616648
TI  - Structural evaluation of sugar cane bagasse steam pretreated in the presence of
      CO2 and SO2.
AB  - BACKGROUND: Previous studies on the use of SO2 and CO2 as impregnating agent for
      sugar cane bagasse steam treatment showed comparative and promising results
      concerning the cellulose enzymatic hydrolysis and the low formation of the
      inhibitors furfural and hydroxymethylfurfural for the use of CO2 at 205 degrees
      C/15 min or SO2 at 190 degrees C/5 min. In the present study sugar cane bagasse
      materials pretreated as aforementioned were analyzed by scanning and transmission
      electron microscopy (SEM and TEM), X-Ray Diffraction (XRD) and Infrared (FTIR
      spectroscopy) aiming a better understanding of the structural and chemical
      changes undergone by the pretreated materials. RESULTS: SEM and TEM data showed
      that the structural modifications undergone by the pretreatment with CO2 were
      less pronounced in comparison to that using SO2, which can be directly related to
      the combined severity of each pretreatment. According to XRD data, untreated
      bagasse showed, as expected, a lower crystallinity index (CI = 48.0%) when
      compared to pretreated samples with SO2 (CI = 65.5%) or CO2 (CI = 56.4%), due to
      the hemicellulose removal of 68.3% and 40.5%, respectively. FTIR spectroscopy
      supported SEM, TEM and XRD results, revealing a more extensive action of SO2.
      CONCLUSIONS: The SEM, TEM, XRD and FTIR spectroscopy techniques used in this work
      contributed to structural and chemical analysis of the untreated and pretreated
      bagasse. The images from SEM and TEM can be related to the severity of SO2
      pretreatment, which is almost twice higher. The crystallinity index values
      obtained from XRD showed that pretreated materials have higher values when
      compared with untreated material, due to the partial removal of hemicellulose
      after pretreatment. FTIR spectroscopy supported SEM, TEM and XRD results. CO2 can
      actually be used as impregnating agent for steam pretreatment, although the
      present study confirmed a more extensive action of SO2.

PMID- 22616649
TI  - Preface: special issue commemorating the 50th anniversary of the Department of
      Pharmacology at the University of Alberta.

PMID- 22616650
TI  - Deep-sea bacteria enriched by oil and dispersant from the Deepwater Horizon
      spill.
AB  - The Deepwater Horizon oil spill resulted in a massive influx of hydrocarbons into
      the Gulf of Mexico (the Gulf). To better understand the fate of the oil, we
      enriched and isolated indigenous hydrocarbon-degrading bacteria from deep,
      uncontaminated waters from the Gulf with oil (Macondo MC252) and dispersant used
      during the spill (COREXIT 9500). During 20 days of incubation at 5 degrees C,
      CO(2)  evolution, hydrocarbon concentrations and the microbial community
      composition were determined. Approximately 60% to 25% of the dissolved oil with
      or without COREXIT, respectively, was degraded, in addition to some hydrocarbons
      in the COREXIT. FeCl(2)  addition initially increased respiration rates, but not
      the total amount of hydrocarbons degraded. 16S rRNA gene sequencing revealed a
      succession in the microbial community over time, with an increase in abundance of
      Colwellia and Oceanospirillales during the incubations. Flocs formed during
      incubations with oil and/or COREXIT in the absence of FeCl(2) . Synchrotron
      radiation-based Fourier transform infrared (SR-FTIR) spectromicroscopy revealed
      that the flocs were comprised of oil, carbohydrates and biomass. Colwellia were
      the dominant bacteria in the flocs. Colwellia sp. strain RC25 was isolated from
      one of the enrichments and confirmed to rapidly degrade high amounts
      (approximately 75%) of the MC252 oil at 5 degrees C. Together these data
      highlight several features that provide Colwellia with the capacity to degrade
      oil in cold, deep marine habitats, including aggregation together with oil
      droplets into flocs and hydrocarbon degradation ability.

PMID- 22616651
TI  - Effects of ions on hydrogen-bonding water networks in large aqueous nanodrops.
AB  - Ensemble infrared photodissociation (IRPD) spectra in the hydrogen stretch region
      (~2800-3800 cm(-1)) are reported for aqueous nanodrops containing ~250 water
      molecules and either SO(4)(2-), I(-), Na(+), Ca(2+), or La(3+) at 133 K. Each
      spectrum has a broad feature in the bonded-OH region (~2800-3500 cm(-1)) and a
      sharp feature near 3700 cm(-1), corresponding to the free-OH stretch of surface
      water molecules that accept two hydrogen bonds and donate one hydrogen bond (AAD
      water molecules). A much weaker band corresponding to AD surface water molecules
      is observed for all ions except SO(4)(2-). The frequencies of the AAD free-OH
      stretch red-shift with increasingly positive charge, consistent with a Stark
      effect as a result of the ion's electric field at the droplet surface, and from
      which the corresponding frequency for water molecules at the surface of neutral
      nanodrops of this size is estimated to be 3699.3-3700.1 cm(-1). The intensity of
      the AAD band increases with increasing positive charge, consistent with a greater
      population of AAD water molecules for the more positively charged nanodrops. The
      spectra of M(H(2)O)(~250), M = Na(+) and I(-), are very similar, whereas those
      for Ca(2+) and SO(4)(2-) have distinct differences. These results indicate that
      the monovalent ions do not affect the hydrogen-bonding network of the majority of
      water molecules whereas this network is significantly affected in nanodrops
      containing the multivalent ions. The ion-induced effect on water structure
      propagates all the way to the surface of the nanodrops, which is located more
      than 1 nm from the ion.

PMID- 22616652
TI  - Susceptibility to dysphagia after fundoplication revealed by novel automated
      impedance manometry analysis.
AB  - BACKGROUND: Conventional measures of esophageal pressures or bolus transport fail
      to identify patients at risk of dysphagia after laparoscopic fundoplication.
      METHODS: Liquid and viscous swallows were evaluated with impedance/manometry in
      19 patients with reflux disease before and after surgery. A new method of
      automated impedance manometry (AIM) analysis correlated esophageal pressure with
      impedance data and automatically calculated a range of pressure and bolus
      movement variables. An iterative analysis determined whether any variables were
      altered in relation to dysphagia. Standard measures of esophago-gastric junction
      pressure, bolus presence time, and total bolus transit time were also evaluated.
      KEY RESULTS: At 5 months postop, 15 patients reported some dysphagia, including 7
      with new-onset dysphagia. For viscous boluses, three AIM-derived pressure-flow
      variables recorded preoperatively varied significantly in relation to
      postoperative dysphagia. These were: time from nadir esophageal impedance to peak
      esophageal pressure (TNadImp-PeakP), median intra-bolus pressure (IBP, mmHg), and
      the rate of bolus pressure rise (IBP slope, mmHgs(-1) ). These variables were
      combined to form a dysphagia risk index (DRI=IBP*IBP_slope/TNadImp-PeakP). DRI
      values derived from preoperative measurements were significantly elevated in
      those with postoperative dysphagia (DRI=58, IQR=21-408 vs no dysphagia DRI=9,
      IQR=2-19, P<0.02). A DRI >14 was optimally predictive of dysphagia (sensitivity
      75% and specificity 93%). CONCLUSIONS & INFERENCES: Before surgery, a greater and
      faster compression of a swallowed viscous bolus with less bolus flow time relates
      to postoperative dysphagia. Thus, susceptibility to postfundoplication dysphagia
      is related to a pre-existing sub-clinical variation of esophageal function.

PMID- 22616654
TI  - Stereotactic Ablative Radio Therapy (SABR) followed by immunotherapy a challenge
      for individualized treatment of metastatic solid tumours.
AB  - Combination strategies surely play a crucial role in treatment of cancer.
      Stereotactic ablative radiotherapy (SABR) has been described to induce abscopal
      effects particularly in renal cell cancer metastases. This effect is a reaction
      induced following irradiation of tumour tissue and occurring in another
      metastatic location outside the treatment field. However, this effect is limited
      and occurs sparsely in about 1-5% of patient. We are planning to improve the
      clinical outcome of this treatment in metastatic solid tumours by combining SABR
      with sequential immunotherapeutic treatments including vaccination strategies,
      adoptive cell therapy, cytokine therapy, or anti-CTLA-4 therapy.

PMID- 22616653
TI  - Adipokines, hormonal parameters, and cardiovascular risk factors: similarities
      and differences between patients with erectile dysfunction of arteriogenic and
      nonarteriogenic origin.
AB  - INTRODUCTION: Erectile dysfunction (ED) is often associated with metabolic
      disorders. Leptin and adiponectin are adipose tissue-derived hormones involved in
      the regulation of metabolic homeostasis and considered important players in the
      relationship among obesity and cardiovascular diseases. AIM: Leptin, adiponectin,
      leptin to adiponectin ratio (L/A), and their correlation with hormonal and
      metabolic parameters were examined in male with arteriogenic- (A-ED) and
      nonarteriogenic-ED (NA-ED). MAIN OUTCOME MEASURES: Biochemical, metabolic, and
      hormonal parameters of men with A-ED were compared with those of male with NA-ED.
      METHODS: Diagnosis of ED was based on the International Index of Erectile
      Function Score. Its etiology was classified with penile echo-color Doppler at
      baseline and after intracavernous injection of prostaglandin E1. Leptin and
      adiponectin were measured by enzyme-linked immunosorbent assay. RESULTS: In A-ED
      subjects, increased levels of insulin, glycated hemoglobin, homeostasis model
      assessment of insulin resistance (HOMA-IR) index, body mass index (BMI), leptin,
      and L/A and decreased levels of total, free, and bioavailable testosterone were
      observed compared with NA-ED subjects. A trend toward lower estradiol level was
      also present in A-ED patients, even if not statistically significant. Reduced
      levels of adiponectin have been observed in both groups compared with patients
      without ED. Leptin and L/A correlated similarly with several parameters
      (negatively with testosterone/estradiol ratio and positively with BMI, insulin,
      HOMA-IR, and 17-beta estradiol). L/A resulted further correlated negatively with
      high-density lipoprotein and positively with triglycerides. CONCLUSIONS: Not all
      ED cases are similar. In fact, A-ED patients display a more complicated metabolic
      status characterized by overweight and obesity and associated to sexual hormone
      alteration. Whether changes in body composition and modulation of adipokine
      levels can improve local endothelial function need further investigation.

PMID- 22616656
TI  - Decision making for risk management: a comparison of graphical methods for
      presenting quantitative uncertainty.
AB  - Previous research has shown that people err when making decisions aided by
      probability information. Surprisingly, there has been little exploration into the
      accuracy of decisions made based on many commonly used probabilistic display
      methods. Two experiments examined the ability of a comprehensive set of such
      methods to effectively communicate critical information to a decision maker and
      influence confidence in decision making. The second experiment investigated the
      performance of these methods under time pressure, a situational factor known to
      exacerbate judgmental errors. Ten commonly used graphical display methods were
      randomly assigned to participants. Across eight scenarios in which a
      probabilistic outcome was described, participants were asked questions regarding
      graph interpretation (e.g., mean) and made behavioral choices (i.e., act; do not
      act) based on the provided information indicated that decision-maker accuracy
      differed by graphical method; error bars and boxplots led to greatest mean
      estimation and behavioral choice accuracy whereas complementary cumulative
      probability distribution functions were associated with the highest probability
      estimation accuracy. Under time pressure, participant performance decreased when
      making behavioral choices.

PMID- 22616655
TI  - The pharmacokinetics and pharmacodynamics of single dose (R)- and (S)-warfarin
      administered separately and together: relationship to VKORC1 genotype.
AB  - AIMS: 1) To determine the pharmacokinetics and pharmacodynamics of (R)- and (S)
      warfarin given alone and in combination and 2) to determine whether the relative
      potency of (R)- and (S)-warfarin is dependent on VKORC1 genotype. METHODS: A
      three way crossover study was conducted in which 17 healthy male subjects
      stratified by VKORC1 1173 C>T genotype and all CYP2C9 1*/1* received (R)-warfarin
      80 mg, (S)-warfarin 12.5 mg and rac-warfarin sodium 25 mg. Plasma (R)- and (S)
      warfarin unbound and total concentrations and prothrombin time were determined at
      multiple time points to 168 h. RESULTS: Pharmacokinetic parameters for (R)- and
      (S)-warfarin were similar to the literature. (R)-warfarin 80 mg alone resulted in
      a mean AUC(PT) (0,168 h) of 3550 s h (95% CI 3220, 3880). Rac-warfarin sodium 25
      mg containing (S)-warfarin 11.7 mg produced a greater effect on AUC(PT) (0,168 h)
      than (S)-warfarin 12.5 mg (mean difference 250 s.h, 95% CI 110, 380, P < 0.002)
      given alone. In a mixed effects model the ratio of response between (R)- and (S)
      warfarin (AUC(PT((R)-warfarin)) : AUC(PT((S)-warfarin))) was 1.21 fold higher
      (95% CI 1.05, 1.41, P < 0.02) in subjects of VKORC1 TT genotype compared with the
      CC genotype. CONCLUSIONS: (R)-warfarin has a clear PD effect and contributes to
      the hypoprothrombinaemic effect of rac-warfarin. VKORC1 genotype is a covariate
      of the relative R/S potency relationship. Prediction of drug interactions with
      warfarin needs to consider effects on (R)-warfarin PK and VKORC1 genotype.

PMID- 22616657
TI  - Exploring stress-induced cognitive impairment in middle aged, centrally obese
      adults.
AB  - Extensive research has shown that psychosocial stress can induce cognitive
      impairment. However, few studies have explored impairment following acute stress
      exposure in individuals with central obesity. Central obesity co-occurs with
      glucocorticoid excess and can lead to elevated cortisol responses to stress. It
      is not clear whether centrally obese individuals exhibit greater cognitive
      impairment following acute stress. Cortisol responses to stress versus no-stress
      control were compared in 66 high- and low waist to hip ratio (WHR) middle-aged
      adults (mean age of 46 +/- 7.17 years). Cognitive performance post exposure was
      assessed using Cambridge Automated Neuropsychological Test Battery. It was
      hypothesised that high WHR would exhibit greater cortisol in response to stress
      exposure and would show poorer cognitive performance. Males, particularly of high
      WHR, tended to secrete greater cortisol during stress exposure. Exposure to
      stress and increasing WHR were specifically associated with poorer performance on
      declarative memory tasks (spatial recognition memory and paired associates
      learning). These data tentatively suggest a reduction in cognitive performance in
      those with central obesity following exposure to acute stress. Further research
      is needed to elucidate the effects of stress on cognition in this population.

PMID- 22616658
TI  - Lupus mastitis without systemic disease: unusual imaging findings including MRI.

PMID- 22616659
TI  - Cationic thermosensitive liposomes: a novel dual targeted heat-triggered drug
      delivery approach for endothelial and tumor cells.
AB  - Developing selectively targeted and heat-responsive nanocarriers holds paramount
      promises in chemotherapy. We show that this can be achieved by designing
      liposomes combining cationic charged and thermosensitive lipids in the bilayer.
      We demonstrated, using flow cytometry, live cell imaging, and intravital optical
      imaging, that cationic thermosensitive liposomes specifically target angiogenic
      endothelial and tumor cells. Application of mild hyperthermia led to a rapid
      content release extra- and intracellularly in two crucial cell types in a solid
      tumor.

PMID- 22616660
TI  - Improved dielectric and mechanical properties of polystyrene-hybrid silica sphere
      composite induced through bifunctionalization at the interface.
AB  - Hybrid silica spheres (HS) of size 270-350 nm with vinyl and aminopropyl surface
      groups were incorporated in polystyrene (PS), and its effect on dielectric
      properties, coefficient of thermal expansion (CTE), and strength of PS-HS
      composite was studied. Incorporation of HS in PS followed a decrease in the
      dielectric constant from 3.2 for PS to 2.6 for composite with 7.5 vol % HS. The
      decrease in the dielectric constant was attributed to (i) increased interfacial
      porosity, (ii) formation of anhydrous HS having low dielectric constant, during
      hot processing of the composites, and (iii) dispersion and preservation of the
      anhydrous HS in the hydrophobic matrix. The dielectric constant of the composites
      with HS content up to 7.5 vol % does not vary much with temperature in the range
      from -20 to 65  degrees C. These composites also exhibited reduced CTE and
      improved flexural strength/stiffness due to good interfacial bonding through HS
      vinyl groups and dispersion of the filler in the matrix. The dielectric loss
      increased with HS content, and the loss measured for 7.5 vol % PS-HS composite
      was 6 * 10(-3), as compared to 10(-4) for PS. At HS loading above 7.5 vol %, the
      tendency of HS to agglomerate and form percolated structure lead to an increase
      in the dielectric constant and decrease in the mechanical properties of the
      composites.

PMID- 22616661
TI  - Fully biodegradable and biorenewable ternary blends from polylactide, poly(3
      hydroxybutyrate-co-hydroxyvalerate) and poly(butylene succinate) with balanced
      properties.
AB  - A ternary blend of entirely biodegradable polymers, namely polylactide (PLA),
      poly(3-hydroxybutyrate-co-hydroxyvalerate) (PHBV), and poly(butylene succinate)
      (PBS), was first melt-compounded in an effort to prepare novel fully
      biodegradable materials with an excellent balance of properties. The miscibility,
      morphology, thermal behavior, mechanical properties, and thermal resistance of
      the blends were investigated. DMA analysis revealed that PHBV and PLA showed some
      limited miscibility with each other, but PBS is immiscible with PLA or PHBV.
      Minor phase-separated structure was observed from SEM for all the blends
      composition except PHBV/PLA/PBS 60/30/10 blend, which formed a typical mixture of
      core-shell morphology. The morphologies were verified by analysis of the
      spreading coefficients. Excellent stiffness-toughness balance was achieved by
      ternary blends of PLA, PHBV, and PBS. Significant enhancement of the toughness
      and flexibility of PLA was achieved by the incorporation of PBS and PHBV without
      sacrificing the strength apparently. Both the stiffness and toughness were
      improved for PHBV in the ternary blends with PHBV as matrix. The crystallization
      of the PLA and PBS were enhanced by presence of PHBV in the blends, while the
      crystallization of PHBV was confined by PLA and PBS phases. Moreover, the thermal
      resistances and melt flow properties of the materials were also studied by
      analysis of the heat deflection temperature (HDT) and melt flow index (MFI) value
      in the work. 

PMID- 22616662
TI  - Real-time stochastic detection of multiple neurotransmitters with a protein
      nanopore.
AB  - The detection of several different neurotransmitters with the same sensor in real
      time would be a powerful asset to the field of neurochemistry. We have developed
      a detector for a broad range of neurotransmitters including amino acids,
      catecholamines, and nucleotides, which relies on the reversible binding of the
      analytes to a copper(II) complex within an engineered protein nanopore.

PMID- 22616663
TI  - Adjunctive re-dilation for early cicatrization after punctoplasty.
AB  - PURPOSE: To evaluate punctoplasty outcomes with adjunctive in-office probing of
      early post-procedure cicatricial changes. METHOD: Retrospective analysis of all
      eyes undergoing 3-snip punctoplasty by a single surgeon between August 1,2008 and
      June 30, 2011. RESULTS: Twenty-two patients were eligible for this study. Twenty
      eight eyes (15 right, 13 left) underwent punctoplasty. Twenty-three eyes
      underwent in-office post-procedure dilation for early cicatricial changes.
      Anatomical success was achieved in 22 patients (100%). Twenty-one patients
      (95.5%) reported improvement in epiphora. CONCLUSIONS: Functional and anatomical
      success rates after punctoplasty may be improved by close post-procedure follow
      up with in-office re-dilation for recurrent punctal cicatrization.

PMID- 22616664
TI  - High frequency of overlap between functional dyspepsia and overactive bladder.
AB  - BACKGROUND: Overactive bladder syndrome (OAB) is defined as a symptom complex
      comprising urgency, with or without urge incontinence, and usually frequency and
      nocturia. The association between irritable bowel syndrome (IBS) and bladder
      symptoms has been reported. This study is designed to investigate whether
      functional dyspepsia (FD), like IBS, is associated with OAB. METHODS: A web
      surveys containing questions about OAB, FD, IBS, and demographics were completed
      by 5494 public individuals (2302 men and 3192 women) who have no history of
      severe illness. The prevalence and overlap of OAB, FD, and IBS were examined. KEY
      RESULTS: Among participants with FD, 20.5% could also be diagnosed with OAB (odds
      ratio [OR]: 2.85; 95% confidence interval [CI]: 2.21-3.67). Although concomitant
      FD and IBS were more strongly associated with OAB (OR: 4.34; 95% CI: 2.81-6.73),
      OAB was also highly prevalent among participants with FD but without IBS (OR:
      3.09; 95% CI: 2.29-4.18). Among participants with FD, an overlapping OAB
      condition was more prevalent in those with both postprandial distress syndrome
      (PDS) and epigastric pain syndrome (EPS) (OR: 3.75; 95% CI: 2.48-5.67) than in
      those with PDS or EPS alone. Among participants with OAB, the severity of bladder
      symptoms was greater in participants with dyspeptic symptoms than without them.
      CONCLUSIONS & INFERENCES: Overactive bladder syndrome is common among FD
      patients, even if they do not have IBS. To improve FD patients' quality of life,
      it will be important to provide management for OAB.

PMID- 22616665
TI  - Ingesting a high-dose carbohydrate solution during the cycle section of a
      simulated Olympic-distance triathlon improves subsequent run performance.
AB  - The well-established ergogenic benefit of ingesting carbohydrates during single
      discipline endurance sports has only been tested once within an Olympic-distance
      (OD) triathlon. The aim of the present study was to compare the effect of
      ingesting a 2:1 maltodextrin/fructose solution with a placebo on simulated OD
      triathlon performance. Six male and 4 female amateur triathletes (age, 25 +/- 7
      years; body mass, 66.8 +/- 9.2 kg; peak oxygen uptake, 4.2 +/- 0.6 L.min(-1))
      completed a 1500-m swim time-trial and an incremental cycle test to determine
      peak oxygen uptake before performing 2 simulated OD triathlons. The swim and
      cycle sections of the main trials were of fixed intensities, while the run
      section was completed as a time-trial. Two minutes prior to completing every
      quarter of the cycle participants consumed 202 +/- 20 mL of either a solution
      containing 1.2 g.min(-1) of maltodextrin plus 0.6 g.min(-1) of fructose at 14.4%
      concentration (CHO) or a sugar-free, fruit-flavored drink (PLA). The time-trial
      was 4.0% +/- 1.3% faster during the CHO versus PLA trial, with run times of 38:43
      +/- 1:10 min:s and 40:22 +/- 1:18 min:s, respectively (p = 0.010). Blood glucose
      concentrations were higher in the CHO versus PLA trial (p < 0.001), while
      perceived stomach upset did not differ between trials (p = 0.555). The current
      findings show that a 2:1 maltodextrin/fructose solution (1.8 g.min(-1) at 14.4%)
      ingested throughout the cycle section of a simulated OD triathlon enhances
      subsequent 10-km run performance in triathletes.

PMID- 22616666
TI  - Smoke-induced signal molecules in bone marrow cells from altered low-density
      lipoprotein receptor-related protein 5 mice.
AB  - Mechanism underlying smoke-induced loss of bone mass is unknown. In this study,
      we hypothesized that protein signals induced by smoking in bone marrow may be
      associated with the loss of bone mass. Using a proteomics approach, we identified
      38 proteins differentially expressed in bone marrow cells from low-density
      lipoprotein receptor-related protein 5 (Lrp5) mice exposed to cigarette smoking.
      Smoking effects on protein expression in bone marrow among three genotypes
      (Lrp5(+/+), Lrp5(G171V), and Lrp5(-/-)) varied. On the basis of the ratio of
      protein expression induced by smoking versus nonsmoking, smoke induced protein
      expression significantly in wild-type mice compared to the other two genotypes
      (Lrp5(G171V) and Lrp5(-/-)). These proteins include inhibitors of beta-catenin
      and proteins associated with differentiation of osteoclasts. We observed that
      S100A8 and S100A9 were overexpressed in human smokers compared to nonsmokers,
      which confirmed the effect of smoking on the expression of two proteins in Lrp5
      mice, suggesting the role of these proteins in bone remodeling. Smoke induced
      expression of S100A8 and S100A9 in a time-dependent fashion, which was opposite
      of the changes in the ratio of OPG/RANKL in bone marrow cells, suggesting that
      the high levels of S100A8 and S100A9 may be associated with smoke-induced bone
      loss by increasing bone resorption.

PMID- 22616667
TI  - Drug-drug interactions involving lysosomes: mechanisms and potential clinical
      implications.
AB  - INTRODUCTION: Many commercially available, weakly basic drugs have been shown to
      be lysosomotropic, meaning they are subject to extensive sequestration in
      lysosomes through an ion trapping-type mechanism. The extent of lysosomal
      trapping of a drug is an important therapeutic consideration because it can
      influence both activity and pharmacokinetic disposition. The administration of
      certain drugs can alter lysosomes such that their accumulation capacity for co
      administered and/or secondarily administered drugs is altered. AREAS COVERED: In
      this review the authors explore what is known regarding the mechanistic basis for
      drug-drug interactions involving lysosomes. Specifically, the authors address the
      influence of drugs on lysosomal pH, volume and lipid processing. EXPERT OPINION:
      Many drugs are known to extensively accumulate in lysosomes and significantly
      alter their structure and function; however, the therapeutic and toxicological
      implications of this remain controversial. The authors propose that drug-drug
      interactions involving lysosomes represent an important potential source of
      variability in drug activity and pharmacokinetics. Most evaluations of drug-drug
      interactions involving lysosomes have been performed in cultured cells and
      isolated tissues. More comprehensive in vivo evaluations are needed to fully
      explore the impact of this drug-drug interaction pathway on therapeutic outcomes.

PMID- 22616668
TI  - Paraoxonase-1 activity and oxidative status in patients with knee osteoarthritis
      and their relationship with radiological and clinical parameters.
AB  - BACKGROUND: The aim of this study was to investigate serum paraoxonase-1 (PON1)
      activity and oxidative/anti-oxidative status in knee osteoarthritis (OA), and
      evaluate their relationship using radiological and clinical parameters. MATERIALS
      AND METHODS: The study population comprised 127 patients with knee OA and 107
      healthy volunteers. Patients with knee OA were divided into four subgroups
      according to the Kellgren-Lawrence (K&L) grading scale. In addition, each patient
      was clinically evaluated by the Western Ontario and McMaster University
      Osteoarthritis Index (WOMAC). Serum PON1 activity was measured
      spectrophotometrically. Oxidative status was assessed by measuring serum lipid
      hydroperoxide (LOOH) and total oxidant status (TOS). Anti-oxidative status was
      assessed by measuring serum free sulfydryl groups (-SH = total thiol) and total
      antioxidant capacity (TAC). Oxidative stress index (OSI) was calculated. Lipid
      parameters were determined by routine laboratory methods. RESULTS: Serum PON1
      activity was significantly lower in the knee OA group compared to the control
      group (p < 0.001), whereas serum LOOH, TOS, and OSI levels of the knee OA group
      were significantly higher than those of the controls (p < 0.001 for all).
      However, TAC and -SH levels did not differ between the two groups (p > 0.05). The
      lowest and highest mean serum PON1 activities were detected in patients with
      grades 4 and 1, respectively (ANOVA p < 0.001). In multiple regression analysis,
      WOMAC score was independently associated with serum PON1 activity (beta = -0.248,
      p = 0.027). CONCLUSIONS: Decreased serum PON1 activity and elevated LOOH, TOS,
      and OSI levels may be associated with knee OA, and serum PON1 activity may be a
      useful adjunctive indicator of the severity of knee OA for follow-up.

PMID- 22616669
TI  - The influence of treatments in daily clinical practice on the Children's
      Dermatology Life Quality Index in juvenile psoriasis: a longitudinal study from
      the Child-CAPTURE patient registry.
AB  - BACKGROUND: Juvenile psoriasis has a negative effect on the quality of life
      (QoL). The influence of treatments on QoL of these children has never been
      investigated before in a prospective observational study. OBJECTIVES: To assess
      the Children's Dermatology Life Quality Index (CDLQI) in a cohort of patients
      with juvenile psoriasis and to evaluate the influence of treatments in daily
      clinical practice on CDLQI. METHODS: We conducted a prospective observational
      study of children with psoriasis from a registry containing daily clinical
      practice data. Before and after treatment, QoL was assessed by the CDLQI and
      disease severity was documented by the Psoriasis Area and Severity Index (PASI).
      Three clusters of treatments were analysed: topical, dithranol and systemic
      therapy. RESULTS: In total, 125 patients were enrolled in the registry. Cross
      sectionally, a mean +/- SD CDLQI score of 7.5 +/- 5.0 and a mean +/- SD PASI of
      7.0 +/- 5.8 were recorded. Itching and problems with treatment had the highest
      impact on the children's QoL. Longitudinally, 85 patients were analysed with a
      total of 137 treatment episodes. All treatments contributed to a significant
      decline in total CDLQI score, with the largest decrease seen in dithranol and
      systemic treatments. A significant correlation was found between DeltaCDLQI and
      DeltaPASI for all treatment modalities. The highest positive impact of treatments
      was found in a decline of itch and sleep disturbance. CONCLUSIONS: In this first
      prospective observational study on CDLQI in juvenile psoriasis, a positive
      influence of treatments in daily clinical practice on QoL was demonstrated.

PMID- 22616670
TI  - Effects of mechanical properties of polymer on ceramic-polymer composite thick
      films fabricated by aerosol deposition.
AB  - Two types of ceramic-polymer composite thick films were deposited on Cu
      substrates by an aerosol deposition process, and their properties were
      investigated to fabricate optimized ceramic-based polymer composite thick films
      for application onto integrated substrates with the advantage of plasticity. When
      polymers with different mechanical properties, such as polyimide (PI) and
      poly(methyl methacrylate) (PMMA), are used as starting powders together with
      alpha-Al2O3 powder, two types of composite films are formed with different
      characteristics - surface morphologies, deposition rates, and crystallite size of
      alpha-Al2O3. Through the results of micro-Vickers hardness testing, it was
      confirmed that the mechanical properties of the polymer itself are associated
      with the performances of the ceramic-polymer composite films. To support and
      explain these results, the microstructures of the two types of polymer powders
      were observed after planetary milling and an additional modeling test was carried
      out. As a result, we could conclude that the PMMA powder is distorted by the
      impact of the Al2O3 powder, so that the resulting Al2O3-PMMA composite film had a
      very small amount of PMMA and a low deposition rate. In contrast, when using PI
      powder, the Al2O3-PI composite film had a high deposition rate due to the
      cracking of PI particles. Consequently, it was revealed that the mechanical
      properties of polymers have a considerable effect on the properties of the
      resulting ceramic-polymer composite thick films.

PMID- 22616671
TI  - Explicit ions condensation around strongly charged polyelectrolytes and spherical
      macroions: the influence of salt concentration and chain linear charge density.
      Monte Carlo simulations.
AB  - The condensation of monovalent counterions and trivalent salt particles around
      strong rigid and flexible polyelectrolyte chains as well as spherical macroions
      is investigated by Monte Carlo simulations. The results are compared with the
      condensation theory proposed by Manning. Considering flexible polyelectrolyte
      chains, the presence of trivalent salt is found to play an important role by
      promoting chain collapse. The attraction of counterions and salt particles near
      the polyelectrolyte chains is found to be strongly dependent on the chain linear
      charge density with a more important condensation at high values. When trivalent
      salt is added in a solution containing monovalent salt, the trivalent cations
      progressively replace the monovalent counterions. Ion condensation around
      flexible chains is also found to be more efficient compared with rigid rods due
      to monomer rearrangement around counterions and salt cations. In the case of
      spherical macroions, it is found that a fraction of their bare charge is
      neutralized by counterions and salt cations. The decrease of the Debye length,
      and thus the increase of salt concentration, promotes the attraction of
      counterions and salt particles at the macroion surface. Excluded volume effects
      are also found to significantly influence the condensation process, which is
      found to be more important by decreasing the ion size.

PMID- 22616672
TI  - Diagnosis and management of rare gastrointestinal lymphomas.
AB  - Primary gastrointestinal (GI) lymphoma is rare, however accounts for 30-40% of
      cases of extranodal lymphoma. Several lymphoma subtypes have a propensity for GI
      tract involvement. Whilst the literature is dominated by data related to the more
      common extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue
      (MALT lymphoma) and diffuse large B-cell lymphoma (DLBCL) of the stomach, this
      review focuses on the rare subtypes of enteropathy-associated T-cell lymphoma
      (EATL), GI follicular lymphoma, mantle cell lymphoma (lymphomatous polyposis
      coli) and extranodal natural killer (NK)/T-cell lymphoma nasal-type (ENKTL). Due
      to its rarity, the majority of data regarding primary GI lymphoma have been
      derived from subgroups of larger cohorts. Clinical characteristics, prognosis and
      management can differ from those of nodal disease, despite corresponding
      histology. We discuss these differences and the challenges associated with
      diagnosis and management of these rare diseases.

PMID- 22616674
TI  - Polyaromatic ribbons from oligo-alkynes via selective radical cascade: stitching
      aromatic rings with polyacetylene bridges.
AB  - Selective radical generation in conjugated oligomeric o-aryleneethynylenes
      initiates an intramolecular cascade which involves five fast radical cyclizations
      followed by aromatization via a 1,5-H shift with a >93% yield per step. This
      radical cascade transformation opens a new avenue for the systematic and
      controlled preparation of functionalized graphene nanoribbons where, potentially,
      each of the peripheral aromatic rings can be different.

PMID- 22616673
TI  - Global tests of P-values for multifactor dimensionality reduction models in
      selection of optimal number of target genes.
AB  - BACKGROUND: Multifactor Dimensionality Reduction (MDR) is a popular and
      successful data mining method developed to characterize and detect nonlinear
      complex gene-gene interactions (epistasis) that are associated with disease
      susceptibility. Because MDR uses a combinatorial search strategy to detect
      interaction, several filtration techniques have been developed to remove genes
      (SNPs) that have no interactive effects prior to analysis. However, the cutoff
      values implemented for these filtration methods are arbitrary, therefore
      different choices of cutoff values will lead to different selections of genes
      (SNPs). METHODS: We suggest incorporating a global test of p-values to filtration
      procedures to identify the optimal number of genes/SNPs for further MDR analysis
      and demonstrate this approach using a ReliefF filter technique. We compare the
      performance of different global testing procedures in this context, including the
      Kolmogorov-Smirnov test, the inverse chi-square test, the inverse normal test,
      the logit test, the Wilcoxon test and Tippett's test. Additionally we demonstrate
      the approach on a real data application with a candidate gene study of drug
      response in Juvenile Idiopathic Arthritis. RESULTS: Extensive simulation of
      correlated p-values show that the inverse chi-square test is the most appropriate
      approach to be incorporated with the screening approach to determine the optimal
      number of SNPs for the final MDR analysis. The Kolmogorov-Smirnov test has high
      inflation of Type I errors when p-values are highly correlated or when p-values
      peak near the center of histogram. Tippett's test has very low power when the
      effect size of GxG interactions is small. CONCLUSIONS: The proposed global tests
      can serve as a screening approach prior to individual tests to prevent false
      discovery. Strong power in small sample sizes and well controlled Type I error in
      absence of GxG interactions make global tests highly recommended in epistasis
      studies.

PMID- 22616678
TI  - Ninth Conversation in Biomolecular Stereodynamics June 20-24, 1995.

PMID- 22616675
TI  - Potentiation of the P2X3 ATP receptor by PAR-2 in rat dorsal root ganglia
      neurons, through protein kinase-dependent mechanisms, contributes to inflammatory
      pain.
AB  - Proinflammatory agents trypsin and mast cell tryptase cleave and activate
      protease-activated receptor-2 (PAR-2), which is expressed on sensory nerves and
      causes neurogenic inflammation. P2X3 is a subtype of the ionotropic receptors for
      adenosine 5'-triphosphate (ATP), and is mainly localized on nociceptors. Here, we
      show that a functional interaction of the PAR-2 and P2X3 in primary sensory
      neurons could contribute to inflammatory pain. PAR-2 activation increased the
      P2X3 currents evoked by alpha, beta, methylene ATP in dorsal root ganglia (DRG)
      neurons. Application of inhibitors of either protein kinase C (PKC) or protein
      kinase A (PKA) suppressed this potentiation. Consistent with this, a PKC or PKA
      activator mimicked the PAR-2-mediated potentiation of P2X3 currents. In the in
      vitro phosphorylation experiments, application of a PAR-2 agonist failed to
      establish phosphorylation of the P2X3 either on the serine or the threonine site.
      In contrast, application of a PAR-2 agonist induced trafficking of the P2X3 from
      the cytoplasm to the plasma membrane. These findings indicate that PAR-2 agonists
      may potentiate the P2X3, and the mechanism of this potentiation is likely to be a
      result of translocation, but not phosphorylation. The functional interaction
      between P2X3 and PAR-2 was also confirmed by detection of the alpha, beta,
      methylene-ATP-evoked extracellular signal-regulated kinases (ERK) activation, a
      marker of neuronal signal transduction in DRG neurons, and pain behavior. These
      results demonstrate a functional interaction of the protease signal with the ATP
      signal, and a novel mechanism through which protease released in response to
      tissue inflammation might trigger the sensation to pain through P2X3 activation.

PMID- 22616681
TI  - The ciprofloxacin target AUC : MIC ratio is not reached in hospitalized patients
      with the recommended dosing regimens.
AB  - AIM: The aim of this study was to determine the ciprofloxacin serum
      concentrations in hospitalized patients and to determine which percentage reached
      the efficacy target of AUC : MIC > 125. Additionally, the influence of
      demographic anthropomorphic and clinical parameters on the pharmacokinetics and
      pharmacodynamics of ciprofloxacin were investigated. METHODS: In serum of 80
      hospitalized patients ciprofloxacin concentrations were measured with reverse
      phase high performance liquid chromatography with fluorescence detection. The
      ciprofloxacin dose was 400-1200 mg day(-1) i.v. in two or three doses depending
      on renal function and causative bacteria. Pharmacokinetic parameters were
      calculated with maximum a posteriori Bayesian estimation (MW?PHARM 3.60). A two
      compartment open model was used. RESULTS: Mean (+/- SD) age was 66 (+/- 17)
      years, the mean clearance corrected for bodyweight was 0.24 l h(-1) kg(-1) and
      the mean AUC was 49 mg l(-1) h. Ciprofloxacin clearance and thus AUC were
      associated with both age and serum creatinine. Of all patients, 21% and 75% of
      the patients, did not reach the proposed ciprofloxacin AUC : MIC > 125 target
      with MICs of 0.25 and 0.5 mg l(-1), respectively. A computer simulated increase
      in the daily dose from 800 mg to 1200 mg, decreased these percentages to 1% and
      37%, respectively. CONCLUSION: A substantial proportion of the hospitalized
      patients did not reach the target ciprofloxacin AUC : MIC and are suboptimally
      dosed with recommended doses. Taking into account the increasing resistance to
      ciprofloxacin worldwide, a ciprofloxacin dose of 1200 mg i.v. daily in patients
      with normal renal function is necessary to reach the targeted AUC : MIC > 125.

PMID- 22616682
TI  - Synchronous bilateral primary breast lymphoma.

PMID- 22616683
TI  - Anorganic bovine-derived hydroxyapatite versus beta-tricalcium phosphate in sinus
      augmentation. A comparative histomorphometric study.
AB  - Abstract   AbstractIntroduction: The choice of augmentation material is a crucial
      factor in sinus augmentation surgery. Bovine-derived hydroxyapatite (BHA) and
      beta-tricalcium phosphate (beta-TCP) have been used successfully in sinus
      augmentation procedures. Choosing one of these materials for sinus augmentation
      is still controversial. The aim of this clinical study was to compare the
      biological performance of the new BHA graft material and the well known synthetic
      beta-TCP material in sinus augmentation procedure.Material and Methods: The study
      consisted of 23 patients (12 male and 11 female) who were either edentulous or
      partially edentulous in the posterior maxilla and required implant placement. A
      total of 23 two-step sinus grafting procedures were performed. BHA was used in 13
      patients and beta-TCP was used in 10 patients. After average of 6.5 months of
      healing bone biopsies were taken from the grafted areas. Undecalcified sections
      were prepared for histomorphometric analysis. Results: The mean new bone
      formation was 30.13+/-3.45% in BHA group and 21.09+/-2.86% in beta-TCP group
      (p=0.001). The mean percentage of residual graft particle area was 31.88+/-6.05%
      and 34.05+/-3.01% for BHA group and beta-TCP group, respectively (p=0.047). The
      mean percentage of soft tissue area was 37.99+/-5.92% in BHA group and 44.86+/
      4.28% in beta-TCP group (p=0.011).Conclusion: Both graft materials demonstrated
      successful biocompatibility and osteoconductivity in sinus augmentation
      procedure. However, BHA appears to be more efficient in osteoconduction when
      compared to beta-TCP.

PMID- 22616684
TI  - Examining the 100-year floodplain as a metric of risk, loss, and household
      adjustment.
AB  - An understudied, but central aspect in understanding flood impacts is the way we
      conceptualize, identify, and delineate risk. The 100-year floodplain is the
      longstanding metric in the United States for determining and acting upon the
      possibility of an area being inundated. This spatial delineation guides local
      planning and development decisions, triggers insurance purchases and other
      household adjustments, and serves as the fundamental indicator for whether it is
      safe to build a structure on a particular site. However, increasing evidence
      suggests that the 100-year floodplain is neither accurate nor sufficient in
      guiding communities and household decisions to mitigate the adverse economic
      impacts of floods. In this perspective, we examine the effectiveness of the 100
      year floodplain as an appropriate marker of risk. First, we review existing
      studies on location and flood damage. Next, we apply these concepts to repetitive
      flood losses data in Harris County, Texas. We conclude that the apparent
      inability of the floodplain designation to effectively capture the likelihood of
      property damage and potential loss of human life in coastal areas has left
      potentially millions of property owners unaware of the flood risk and unprepared
      to mitigate their adverse impacts. Relying on traditional 100-year floodplain
      boundaries, local decision makers are hampered in their ability to ensure
      community development occurs in a resilient manner. Finally, we set forth an
      agenda for future research to better capture the conditions associated with flood
      risk and account for the large percentage of damage outside the designated
      floodplain.

PMID- 22616685
TI  - Nursing interventions on sexual health: validation of the NISH Scale in
      baccalaureate nursing students in Taiwan.
AB  - INTRODUCTION: No widely accepted tool is available to assess nursing
      interventions on patient's sexual health among nursing students. Consequently,
      nursing school faculty cannot determine the sexual healthcare-related skills of
      nursing students. AIM: The aim of this article was to develop and test a scale to
      assess nursing interventions on sexual health. METHODS: A 19-item instrument
      Nursing Interventions on Sexual Health (NISH) was developed using 10 semi
      structured interviews of senior nursing students, expert review, and comparative
      analysis of text and field notes. A total of 198 senior nursing students were
      recruited from two nursing schools in central Taiwan to test the instrument.
      Exploratory factor analysis (EFA) was used to measure construct validity and
      Cronbach's alpha to measure internal consistency. MAIN OUTCOME MEASURES: Validity
      and reliability of the NISH scale based on the Permission, Limited Information,
      Specific Suggestion, and Intensive Therapy (PLISSIT) model. RESULTS: Three
      factors (permission, limited information, and specific suggestion) were retained
      after EFA of the 19 items of NISH. Cronbach's alpha for the subscales increased
      from 0.71-0.93 to 0.74-0.94 and from 0.93 to 0.95 for the total scale, with
      72.42% of the cumulative variance explained by these three factors. Nursing
      students' age (P=0.019) correlated positively with total score. CONCLUSIONS: NISH
      is a useful and reliable scale for assessing the frequency of PLISSIT-related
      behaviors used by nursing students to address patient's sexual health concerns.
      Nursing faculties can use this scale to assess students' performance and find
      their omitted behaviors in clinical practice regarding sexual health care.

PMID- 22616686
TI  - Shoulder rotational profiles in young healthy elite female and male badminton
      players.
AB  - The aim of the present study was to profile shoulder passive range of motion
      (ROM) and isometric strength for external (ER) and internal (IR) rotation as part
      of a preseason screening in adolescent national badminton players. Passive
      external range of motion (EROM) and internal range of motion (IROM) were examined
      on the dominant and nondominant shoulder in 31 adolescent national badminton
      players (12 females and 19 males) with a standard goniometer. Muscle strength was
      examined with a hand-held dynamometer in ER and IR. Total range of motion (TROM =
      EROM+IROM) was lower on the dominant side compared with the nondominant side in
      both groups (P < 0.001). Males were generally stronger than females in all
      strength measurements except for IR on the dominant side (P < 0.01). In females,
      IR dominant side strength was greater compared with IR on the nondominant side (P
      < 0.05). TROM was reduced on the dominant side compared with the nondominant side
      in young elite badminton players, irrespective of gender. No rotational strength
      differences existed between the dominant and nondominant side in male players,
      but in female players a higher IR strength on the dominant side was not balanced
      by a higher ER strength. 

PMID- 22616687
TI  - New structural insights into mechanically interlocked polymers revealed by ion
      mobility mass spectrometry.
AB  - Mechanically interlocked polymers can possess significant additional physical
      properties, in comparison to those associated with their constituent parts. Their
      unique properties make them attractive for a range of potential applications,
      such as as biomaterials and molecular machines. Their efficient and reproducible
      synthesis is therefore of much interest. Both their synthesis and subsequent
      characterization are intriguing yet demanding. The properties of mechanically
      interlocked polymeric systems depend not only on the properties of their
      individual components but also on the topology of the subsequent product. Here
      traveling wave ion mobility mass spectrometry has been used to investigate the
      structural properties of a polyrotaxane system. Ion mobility studies reveal that
      this system remains linear in form with increase in size. Both ion mobility
      studies and tandem mass spectrometry studies indicate that the macrocycle
      preferentially remains associated with the ammonium moiety of the polymeric
      repeat unit and is impeded from moving freely along the axle. This is consistent
      with NMR observations of the average structure. Analysis of mechanically
      interlocked polymers by ion mobility mass spectrometry provides additional
      structural insights into these systems relating to dynamics, heterogeneity, and
      topology. This molecule-specific information is vital in order to understand the
      origin of a system's functional properties.

PMID- 22616688
TI  - Distribution of encapsulated materials in colloidal particles and its impact on
      oxidative stability of encapsulated materials.
AB  - The oxidative stability of encapsulated product is a critical parameter in many
      products from food to pharmaceutical to cosmetic industries. The overall
      objective of this study was to correlate differences in the distribution pattern
      of encapsulated material within solid lipid nanoparticles (SLNs) and
      nanostructured lipid carriers (NLCs) with the relative susceptibility of these
      materials to undergo oxidation. The distribution of an encapsulated lipid soluble
      dye (Nile Red) in SLNs and NLCs was quantitatively measured using fluorescence
      imaging. The relative susceptibility of the encapsulated material to react with
      free radicals generated in the aqueous phase and oxygen from the ambient
      environment was measured using peroxyl radical and oxygen sensitive fluorescent
      dyes encapsulated in the lipid phase of colloidal particles respectively. Imaging
      measurements demonstrate a significant exclusion of the encapsulated dye
      molecules from the lipid core of SLNs as compared to NLCs. Imaging results also
      showed significant differences in the intraparticle distribution of encapsulated
      dye between NLCs containing 1 and 10% liquid lipid. On the basis of these
      differences in distribution, we hypothesized that the relative susceptibility of
      encapsulated material to peroxyl radicals and oxygen would be in the order SLNs >
      1% NLC > 10% NLC. Measurement of relative susceptibility of peroxyl radical
      sensitive dye encapsulated in SLNs and NLCs to peroxyl radicals generated in the
      aqueous phase validated the proposed hypotheses. However, the susceptibility of
      encapsulated oxygen sensitive dye to ambient oxygen was not significantly
      different between SLNs and NLCs. The results of this study demonstrate that
      difference in distribution pattern of encapsulated material within colloidal
      particles can significantly influence the susceptibility of encapsulated material
      to react with free radicals. Overall, this study demonstrates a comprehensive
      approach to characterize the susceptibility of encapsulated materials in
      colloidal particles to oxidation processes.

PMID- 22616689
TI  - Nonlocal effects in the nanofocusing performance of plasmonic tips.
AB  - The nanofocusing performance of plasmonic tips is studied analytically and
      numerically. The effects of electron-electron interactions in the dielectric
      response of the metal are taken into account through the implementation of a
      nonlocal, spatially dispersive, hydrodynamic permittivity. We demonstrate that
      spatial dispersion only slightly modifies the device parameters which maximize
      its field enhancement capabilities. The interplay between nonlocality, tip
      bluntness, and surface roughness is explored. We show that, although spatial
      dispersion reduces the field enhancement taking place at the structure apex, it
      also diminishes the impact that geometric imperfections have on its performance.

PMID- 22616692
TI  - A unified approach to multiple-set canonical correlation analysis and principal
      components analysis.
AB  - Multiple-set canonical correlation analysis and principal components analysis are
      popular data reduction techniques in various fields, including psychology. Both
      techniques aim to extract a series of weighted composites or components of
      observed variables for the purpose of data reduction. However, their objectives
      of performing data reduction are different. Multiple-set canonical correlation
      analysis focuses on describing the association among several sets of variables
      through data reduction, whereas principal components analysis concentrates on
      explaining the maximum variance of a single set of variables. In this paper, we
      provide a unified framework that combines these seemingly incompatible
      techniques. The proposed approach embraces the two techniques as special cases.
      More importantly, it permits a compromise between the techniques in yielding
      solutions. For instance, we may obtain components in such a way that they
      maximize the association among multiple data sets, while also accounting for the
      variance of each data set. We develop a single optimization function for
      parameter estimation, which is a weighted sum of two criteria for multiple-set
      canonical correlation analysis and principal components analysis. We minimize
      this function analytically. We conduct simulation studies to investigate the
      performance of the proposed approach based on synthetic data. We also apply the
      approach for the analysis of functional neuroimaging data to illustrate its
      empirical usefulness.

PMID- 22616691
TI  - Functional annotation of the human fat cell secretome.
AB  - CONTEXT: Recent secretome analyses suggest that human fat cells secrete hundreds
      of proteins (adipokines). OBJECTIVE: We made an overall analysis of their
      potential functional importance. MATERIALS AND METHODS: A secretome of 347
      adipokines was evaluated by in silico analysis of their expression during
      adipocyte differentiation, regulation by obesity and adipose region. The gene
      expression in human adipose tissue was investigated in microarray studies using
      samples from different adipose depots from lean or obese patients. RESULTS: 60%
      of the adipokines were regulated by obesity and 50% between visceral and
      subcutaneous adipose region. Eight adipokines, all novel, scored particularly
      high in the in silico analysis. Among those, four were both regulated by obesity
      and adipose region, namely WNT1-inducible-signaling pathway protein 2,
      transmembrane glycoprotein NMB, inter-alpha-trypsin inhibitor heavy chain H5, and
      complement C4-A. Furthermore, many adipokines were extracellular matrix proteins.
      CONCLUSION: Several novel adipokines have potential important functional features
      warranting in depth analysis.

PMID- 22616693
TI  - Spectroscopic and energetic properties of thorium(IV) molecular clusters with a
      hexanuclear core.
AB  - The spectral and energetic properties of three polynuclear thorium(IV) molecular
      complexes Th(6)(OH)(4)O(4)(H(2)O)(6)(HCOO)(12).nH(2)O (1),
      Th(6)(OH)(4)O(4)(H(2)O)(6)(CH(3)COO)(12).nH(2)O (2), and
      Th(6)(OH)(4)O(4)(H(2)O)(6)(ClCH(2)COO)(12).4H(2)O (3) have been studied. Each
      complex has a hexanuclear core with six 9-coordinate Th(IV) cations bridged by
      four MU(3)-hydroxo and four MU(3)-oxo groups. The +12 core is stabilized by
      twelve bridging carboxylate functionalized organic acid (formate, acetate, and
      chloroacetate) units. The calculated (1)H NMR chemical shifts for the four MU(3)
      hydroxo, water, and formate protons are reported and compared to the experimental
      values. The vibrational frequencies were calculated to aid in the assignment of
      the observed Raman bands. The Mulliken and NBO (natural bond orbital) charges are
      calculated for the Th clusters. The Th atoms are positive and the bridging O and
      O(H) are negative. The analysis of the calculated highest-occupied and lowest
      unoccupied molecular orbitals (HOMO and LUMO) is reported. The average water
      complexation energies, the gas phase, the aqueous and dimethylsulfoxide (DMSO)
      acidities were predicted, and the Th clusters are found to be mild to strong
      acids in gas phase yet they behave as weak acids in solution.

PMID- 22616694
TI  - Great potential of miRNAs as predictive and prognostic markers for cancer.

PMID- 22616695
TI  - The 'sequence everything' approach and personalized clinical decision challenges.

PMID- 22616697
TI  - KRAS mutational test for metastatic colorectal cancer patients: not just a
      technical problem.

PMID- 22616698
TI  - Noninvasive fetal trisomy 21 detection using chromosome-selective sequencing: a
      variation of the molecular counting theme.
AB  - Fetal DNA is present in the plasma of pregnant women. A fetus with trisomy of a
      chromosome will release an increased amount of DNA from that chromosome into
      maternal plasma. Such an increase has previously been measured using methods that
      allow individual DNA molecules to be counted. One such method involves the use of
      random massively parallel sequencing of maternal plasma DNA. As the sequencing
      process is random, sequence tags from a potentially aneuploid chromosome only
      represent a fraction of the sequencing data. The performance of selective
      amplification and sequencing of specific genomic regions is a recently reported
      approach for focusing the sequencing power onto genomic regions of diagnostic
      interest. This article provides a critical analysis of this approach and puts
      this method in the perspective of other recent works in the field.

PMID- 22616699
TI  - The current status of clinical proteomics and the use of MRM and MRM(3) for
      biomarker validation.
AB  - The transfer of biomarkers from the discovery field to clinical use is still,
      despite progress, on a road filled with pitfalls. Since the emergence of
      proteomics, thousands of putative biomarkers have been published, often with
      overlapping diagnostic capacities. The strengthening of the robustness of
      discovery technologies, particularly in mass spectrometry, has been followed by
      intense discussions on establishing well-defined evaluation procedures for the
      identified targets to ultimately allow the clinical validation and then the
      clinical use of some of these biomarkers. Some of the obstacles to the evaluation
      process have been the lack of the availability of quick and easy-to-develop, easy
      to-use, robust, specific and sensitive alternative quantitative methods when
      immunoaffinity-based tests are unavailable. Multiple reaction monitoring (MRM;
      also called selected reaction monitoring) is currently proving its capabilities
      as a complementary or alternative technique to ELISA for large biomarker panel
      evaluation. Here, we present how MRM(3) can overcome the lack of specificity and
      sensitivity often encountered by MRM when tracking minor proteins diluted by
      complex biological matrices.

PMID- 22616700
TI  - Label-free mass spectrometry-based proteomics for biomarker discovery and
      validation.
AB  - For most diseases, better biomarkers are urgently needed to enable (early)
      detection, diagnosis, prognosis, stratification for therapy and response
      monitoring. Proteomics delineates gene products that carry out the majority of
      cellular functions, and thereby may not only yield insight into altered signaling
      pathways in disease, but also yield novel biomarkers. In recent years, great
      progress has been made in mass spectrometry-based analysis of clinical tissues
      and biofluids, with identification and quantification of thousands of proteins
      now becoming increasingly routine. However, biomarker validation and clinical
      translation has turned out to be challenging. In this review, we summarize
      current mass spectrometry-based proteomics strategies for biomarker discovery and
      verification using selected reaction monitoring, with a focus on progress and
      recent applications in clinical material using label-free approaches.

PMID- 22616701
TI  - Metabolomics of urinary tract infection: a new uroscope in town.
AB  - Urinary tract infection (UTI) is a potentially life-threatening infectious
      disease. For rapid directed therapy of UTIs, it is essential to determine the
      causative microorganism. To date, there is no single test that has been proven to
      reliably, rapidly and accurately identify the etiologic organism in UTI. The
      molecular methods for diagnosing the cause of UTI and prognostic development of
      clinically important metabolomic evaluations and their limitations for use in the
      diagnosis and monitoring of infections are discussed in this review article. The
      application of the emerging investigative device NMR spectroscopy as a surrogate
      method for the diagnosis of UTI is also addressed.

PMID- 22616702
TI  - Epigenetics of estrogen receptor-negative primary breast cancer.
AB  - Increasingly, breast cancer is being recognized as a heterogeneous disease
      comprised of molecularly and phenotypically distinct intrinsic tumor subtypes
      with different clinical outcomes. This biological heterogeneity has significant
      implications, particularly as it relates to expression profiling of estrogen
      receptor (ER) status, as classifying breast cancers based on hormone receptor
      expression impacts not only prognosis but also treatment options and long-term
      outcomes. Epigenetics has emerged as a promising field for the assessment of
      hormone receptor status. Epigenetic aberrations have been shown to regulate ER
      and offer reversible targets for development of new therapies. This review covers
      ER-negative breast tumor epigenetic aberrations and summarizes the major
      epigenetic mechanisms governing ER expression and how it impacts treatment of ER
      negative breast cancer.

PMID- 22616704
TI  - The future of molecular diagnostics for drug-resistant tuberculosis.
AB  - The last decade has seen significant advances in tuberculosis diagnostics and
      drug susceptibility testing (DST). During the same time period the prevalence of
      drug-resistant tuberculosis has increased and therefore it has become critical to
      understand DST for medications used to treat multidrug-resistant and extensively
      drug-resistant tuberculosis. This review describes recent molecular diagnostic
      advances for DST. Recommendations are provided for clinicians interpreting
      molecular DST and we describe potential opportunities for the field.

PMID- 22616703
TI  - The cellular origin for malignant glioma and prospects for clinical advancements.
AB  - Glioma remains incurable despite great advancements in medicine. Targeting the
      cell of origin for gliomas could bring great hope for patients. However, as a
      collection of diverse diseases, each subtype of glioma could derive from a
      distinct cell of origin. To resolve such a complex problem, one must use multiple
      research approaches to gain deep insights. Here we review current evidence
      regarding the cell of origin from clinical observations, whole-genome molecular
      pathology and glioma animal models. We conclude that neural stem cells, glial
      progenitors (including oligodendrocyte progenitor cells) and astrocytes could all
      serve as cells of origin for gliomas, and that cells incurring initial mutations
      (cells of mutation) might not transform, while their progeny cells could instead
      transform and act as cells of origin. Further studies with multidisciplinary
      approaches are needed to link each subtype to a particular cell of origin, and to
      develop effective therapies that target the signaling network within these cells.

PMID- 22616705
TI  - Handling and analysis of cells and bioparticles on centrifugal microfluidic
      platforms.
AB  - Microfluidic systems for cell separation and analysis have attracted increasing
      research activity over the past decades. In particular, the prospect of
      integrating all steps from sample preparation to assay readout in a single
      microfluidic cartridge, which is inserted into a compact, portable and
      potentially low-cost instrument, bears great promise to leverage next-generation
      diagnostic products and to advance life-science research with novel cell and
      particle manipulation, and analysis tools. Within the range of microfluidic
      actuation principles available, the centrifugal force is exceptionally well
      suited for cell handling due to its rotationally induced 'artificial gravity
      field', which can be varied over several orders of magnitude and which can
      manipulate bioparticles even in the absence of flow. We will survey how the base
      centrifugal force has been combined with the hydrodynamic Stokes drag, magnetic,
      dielectrophoretic and other forces to enable multidimensional separation and
      manipulation. The same centrifugal microfluidic toolbox has also been applied to
      investigate particles such as biofunctionalized beads, bacteria and multicellular
      microorganisms. This review summarizes the significant progress in modular unit
      operations such as cell removal, filtering, lysis, separation, sorting,
      encapsulation, trapping, assaying, sensing, cytometry and detection, even derived
      from low-cost conventional optical disc drive technology (e.g., CD and DVD),
      towards integrated and automated centrifugal microfluidic platforms for the
      handling and analysis of cells and bioparticles.

PMID- 22616707
TI  - Comparative proteomic analysis of the thermotolerant plant Portulaca oleracea
      acclimation to combined high temperature and humidity stress.
AB  - Elevated temperature and humidity are major environmental factors limiting crop
      yield and distribution. An understanding of the mechanisms underlying plant
      tolerance to high temperature and humidity may facilitate the development of
      cultivars adaptable to warm or humid regions. Under conditions of 90% humidity
      and 35  degrees C, the thermotolerant plant Portulaca oleracea exhibits excellent
      photosynthetic capability and relatively little oxidative damage. To determine
      the proteomic response that occurs in leaves of P. oleracea following exposure to
      high temperature and high humidity, a proteomic approach was performed to
      identify protein changes. A total of 51 differentially expressed proteins were
      detected and characterized functionally and structurally; these identified
      proteins were involved in various functional categories, mainly including
      material and energy metabolism, the antioxidant defense responses, protein
      destination and storage, and transcriptional regulation. The subset of
      antioxidant defense-related proteins demonstrated marked increases in activity
      with exposure to heat and humidity, which led to lower accumulations of H(2)O(2)
      and O(2)(-) in P. oleracea compared with the thermosensitive plant Arabidopsis
      thaliana. The quickly accumulations of proline content and heat-shock proteins,
      and depleting abscisic acid (ABA) via increasing ABA-8'-hydroxylase were also
      found in P. oleracea under stress conditions, that resulted into greater stomata
      conductance and respiration rates. On the basis of these findings, we propose
      that P. oleracea employs multiple strategies to enhance its adaptation to high
      temperature and high-humidity conditions.

PMID- 22616708
TI  - Cartilage restoration in haemophilia: advanced therapies.
AB  - Current treatment of joint cartilage lesions is based either on conventional
      techniques (bone marrow stimulation, osteochondral autograft or allograft
      transplantation) or on newly developed techniques (chondrocyte implantation and
      those based on cell therapy that use bioreactors, growth factors, mesenchymal
      stem cells [MSCs] and genetically modified cells). The aim of this article is to
      review the therapeutic strategies above mentioned and to determine whether the
      chondral damage seen in haemophilia could benefit from any of them. The different
      conventional techniques have shown similar results whereas autologous chondrocyte
      implantation, which is in common use at the present time, has not been shown to
      produce any conclusive results or to lead to the formation of hyaline cartilage.
      MSCs hold promise for the repair of joint cartilage given their differentiation
      capacity and the therapeutic effect. The use of bioreactors and growth factors,
      which stimulate cartilage formation, may optimize such strategies in the context
      of reimplantation of chondrocytes, differentiated MSCs and cartilage progenitor
      cells. The aim of cell therapy is restoration of function through the repair of
      damaged tissue or the stimulation of growth factor synthesis. Implantation of
      autologous chondrocytes or MSCs was up to now able to address only highly
      localized chondral lesions. Adequate control of the differentiation process as
      well as the use of growth factors and appropriate bioreactors could transform
      cell-based therapies into a more efficient and longer term treatment even for
      patients with haemophilia. Nevertheless, raising false expectations in these
      patients should be avoided. There are a number of approaches to cartilage
      restoration in haemophilic arthropathy, which are currently being explored for
      other joint related degenerative disorders. If it can be proven to be effective
      for the disorders in which clinical trials are ongoing and costs could be
      limited, it might be an useful palliative approach to haemophilic arthropathy.
      However, we still have a long way to go for use in haemophilic arthropathy.

PMID- 22616709
TI  - Microfabricated gas chromatograph for on-site determination of trichloroethylene
      in indoor air arising from vapor intrusion. 1. Field evaluation.
AB  - Results are presented of inaugural field tests of two identical prototype
      microfabricated gas chromatographs (MUGC) adapted for the in situ determination
      of trichloroethylene (TCE) in indoor air in support of vapor intrusion (VI)
      investigations. Each MUGC prototype has a pretrap and partially selective high
      volume sampler of conventional design, a micromachined-Si focuser for injection,
      dual micromachined-Si columns for separation, and an integrated array of four
      microscale chemiresistors with functionalized gold nanoparticle interface films
      for multichannel detection. Scrubbed ambient air is used as the carrier gas.
      Field-generated calibration curves were linear for injected TCE masses of 26-414
      ng (4.8-77 ppb.L; r(2) > 0.98) and the projected single-sensor detection limit
      was 0.052 ppb for an 8-L air sample collected and analyzed in 20 min. Consistent
      performance between the prototypes and good medium-term stability were shown.
      Above the mitigation action level (MAL) of 2.3 ppb for the field-test site, MUGC
      TCE determinations fell within +/-25% of those from the reference method for 21
      of 26 measurements, in the presence of up to 37 documented background VOCs. Below
      the MAL, positive biases were consistently observed, which are attributable to
      background VOCs that were unresolvable chromatographically or by analysis of the
      sensor-array response patterns. Results demonstrate that this type of MUGC
      instrument could serve the need for routine TCE determinations in VI-related
      assessment and mitigation efforts.

PMID- 22616710
TI  - Mantle-cell lymphoma in the elderly: is it time to CHOP and change?

PMID- 22616711
TI  - Postextraction implant in sites with endodontic infection as an alternative to
      endodontic retreatment: a review of literature.
AB  - Abstract   Objective: the aim of this literature review was to evaluate the
      outcomes of implants placed after extraction of teeth with infections of
      endodontic origin.Study design: an electronic search was performed through
      electronic databases (Medline and EMBASE) using the terms "immediate implant",
      "post-extractive implants", "endodontic infection", "infected site", "extraction
      socket" combined with the use of Boolean operators ("AND" and "OR"). Only
      articles on human subjects were considered. At least 12 month of mean follow-up
      was required for inclusion. No restriction was placed regarding study
      design.Results: Ten studies were included in this review. Survival rates ranged
      from 92% to 100%. A total of 497 implants were placed in sites with endodontic
      infection. In nine studies the use of bone substitutes was associated with
      immediate implant placement.Conclusion: because of the low number of included
      study and the heterogeneity in study design, more well-designed studies are
      required in order to assess relevance of this treatment alternative.

PMID- 22616712
TI  - Nanotag luminescent fingerprint anti-counterfeiting technology.
AB  - We describe a method to fabricate, transfer and validate via image processing
      nanofibre-based, unique security marks ('nanotags') for anti-counterfeiting
      purposes. Epitaxial surface growth of oligophenylenes on a heated muscovite mica
      crystal results in a thin film of mutually aligned nanofibres with dimensions of
      tens of nanometres in height, hundreds of nanometres in width and tens to
      hundreds of micrometres in length. By applying a shadow mask, a film pattern is
      generated which contains only sparse, randomly grown nanofibres, which in turn
      represent a unique 'fingerprint' of the growth area. This fingerprint can be
      transferred on an adhesive tape as a label of a product, imaged using low
      magnification microscopy, digitalised and stored in a database. Infrared surface
      heating, enforced cooling and load lock transfer makes the fabrication process
      fast and scalable to mass production.

PMID- 22616713
TI  - Effect of 1,25(OH)2 vitamin D3 on cytokine production by endometrial cells of
      women with repeated implantation failure.
AB  - Repeated implantation failure (RIF) is a worldwide health problem that imposes a
      great deal of cost on patients and health care system. Vitamin D(3) has been
      proposed to have positive impact on the process of implantation. The present
      study was performed to compare the effect of 1,25-dihydroxy vitamin D(3)
      (1,25(OH)(2)D(3)) on cytokine production by endometrial cells of women with RIF
      and healthy fertile controls. Whole endometrial cells (WECs) and endometrial
      stromal cells (ESCs) from RIF and normal fertile women were treated with
      1,25(OH)(2)D(3). The levels of IL-10, TGF-beta, IFNgamma, Il-6, IL-8 and IL-17 in
      culture supernatants were assayed by ELISA. Also, ability of the cells from both
      groups to produce 1,25(OH)(2)D(3) was evaluated and compared. 1,25(OH)(2)D(3)
      down-regulated cytokine production in WECs from both groups except for IL-8 which
      was upraised. Similar trends were also observed in ESCs except up-regulation of
      TGF-beta in RIF group. Endometrial cells of both groups had comparable capacity
      to produce 1,25(OH)(2)D(3). Based on the minimal differential immunoregulatory
      effect of vitamin D(3) on endometrial cells from RIF and control women, it may be
      suggested that circulating levels of maternal vitamin D(3) be the subject of
      further investigation.

PMID- 22616714
TI  - Quantitative risk assessment of human salmonellosis in Canadian broiler chicken
      breast from retail to consumption.
AB  - The current quantitative risk assessment model followed the framework proposed by
      the Codex Alimentarius to provide an estimate of the risk of human salmonellosis
      due to consumption of chicken breasts which were bought from Canadian retail
      stores and prepared in Canadian domestic kitchens. The model simulated the level
      of Salmonella contamination on chicken breasts throughout the retail-to-table
      pathway. The model used Canadian input parameter values, where available, to
      represent risk of salmonellosis. From retail until consumption, changes in the
      concentration of Salmonella on each chicken breast were modeled using equations
      for growth and inactivation. The model predicted an average of 318 cases of
      salmonellosis per 100,000 consumers per year. Potential reasons for this
      overestimation were discussed. A sensitivity analysis showed that concentration
      of Salmonella on chicken breasts at retail and food hygienic practices in private
      kitchens such as cross-contamination due to not washing cutting boards (or
      utensils) and hands after handling raw meat along with inadequate cooking
      contributed most significantly to the risk of human salmonellosis. The outcome
      from this model emphasizes that responsibility for protection from Salmonella
      hazard on chicken breasts is a shared responsibility. Data needed for a
      comprehensive Canadian Salmonella risk assessment were identified for future
      research.

PMID- 22616715
TI  - Genetic variation in IL-6 and TNF-alpha genes with risk of breast cancer in a
      Saudi population-based case-control study.

PMID- 22616716
TI  - Probing single biomolecules in solution using the anti-Brownian electrokinetic
      (ABEL) trap.
AB  - Single-molecule fluorescence measurements allow researchers to study asynchronous
      dynamics and expose molecule-to-molecule structural and behavioral diversity,
      which contributes to the understanding of biological macromolecules. To provide
      measurements that are most consistent with the native environment of
      biomolecules, researchers would like to conduct these measurements in the
      solution phase if possible. However, diffusion typically limits the observation
      time to approximately 1 ms in many solution-phase single-molecule assays.
      Although surface immobilization is widely used to address this problem, this
      process can perturb the system being studied and contribute to the observed
      heterogeneity.  Combining the technical capabilities of high-sensitivity single
      molecule fluorescence microscopy, real-time feedback control and electrokinetic
      flow in a microfluidic chamber, we have developed a device called the anti
      Brownian electrokinetic (ABEL) trap to significantly prolong the observation time
      of single biomolecules in solution. We have applied the ABEL trap method to
      explore the photodynamics and enzymatic properties of a variety of biomolecules
      in aqueous solution and present four examples: the photosynthetic antenna
      allophycocyanin, the chaperonin enzyme TRiC, a G protein-coupled receptor
      protein, and the blue nitrite reductase redox enzyme. These examples illustrate
      the breadth and depth of information which we can extract in studies of single
      biomolecules with the ABEL trap.  When confined in the ABEL trap, the
      photosynthetic antenna protein allophycocyanin exhibits rich dynamics both in its
      emission brightness and its excited state lifetime. As each molecule
      discontinuously converts from one emission/lifetime level to another in a
      primarily correlated way, it undergoes a series of state changes.  We studied the
      ATP binding stoichiometry of the multi-subunit chaperonin enzyme TRiC in the ABEL
      trap by counting the number of hydrolyzed Cy3-ATP using stepwise photobleaching.
      Unlike ensemble measurements, the observed ATP number distributions depart from
      the standard cooperativity models.  Single copies of detergent-stabilized G
      protein-coupled receptor proteins labeled with a reporter fluorophore also show
      discontinuous changes in emission brightness and lifetime, but the various states
      visited by the single molecules are broadly distributed. As an agonist binds, the
      distributions shift slightly toward a more rigid conformation of the protein.  By
      recording the emission of a reporter fluorophore which is quenched by reduction
      of a nearby type I Cu center, we probed the enzymatic cycle of the redox enzyme
      nitrate reductase. We determined the rate constants of a model of the underlying
      kinetics through an analysis of the dwell times of the high/low intensity levels
      of the fluorophore versus nitrite concentration.

PMID- 22616717
TI  - Editorial comment to initial operative experience of single-port retroperitoneal
      laparoscopic nephrectomy.

PMID- 22616719
TI  - The leukotriene receptor antagonist montelukast and aortic stenosis.

PMID- 22616718
TI  - Differential expression of breast cancer-associated genes between stage- and age
      matched tumor specimens from African- and Caucasian-American Women diagnosed with
      breast cancer.
AB  - BACKGROUND: Recent studies suggest that the poorer breast cancer outcome observed
      in African-American women (AAW) may, in part, result from underlying molecular
      factors. The purpose of this study was to investigate gene expression differences
      between Caucasian-American women (CAW) and AAW that may contribute to this poorer
      prognosis. METHODS: The expression of 84 genes involved in breast carcinoma
      prognosis, response to therapy, estrogen signaling, and tumor aggressiveness was
      assessed in age- and stage-matched CAW and AAW paraffin-embedded breast cancer
      specimens. The Wilcoxon-Mann-Whitney Test was used to identify genes with a
      significant difference in expression between CAW and AAW. To determine if the
      differentially expressed genes could segregate between the CAW and AAW, we
      performed semi-supervised principal component analysis (SSPCA). RESULTS: Twenty
      genes were differentially expressed between AAW and CAW. SSPCA incorporating
      these 20 genes segregated AAW and CAW into two distinct groups. AAW were
      significantly (p < 0.05) more likely to display aberrations in G(1)/S cell-cycle
      regulatory genes, decreased expression of cell-adhesion genes, and low to no
      expression of ESR1, PGR, ERBB2 and estrogen pathway targets. CONCLUSIONS: The
      gene expression differences identified between AAW and CAW may contribute to more
      aggressive disease, resistance to therapy, enhanced metastatic potential and poor
      clinical outcome. These findings support the hypothesis that breast cancer
      specimens collected from AAW display distinct gene expression differences
      compared to similar tissues obtained from CAW. Additional population-based
      studies are necessary to determine if these gene expression variations contribute
      to the highly aggressive and treatment-resistant breast cancer phenotype
      frequently observed in AAW.

PMID- 22616720
TI  - Serologic evidence for human hantavirus infection in Peru.
AB  - While human illness associated with hantavirus infection has been documented in
      many countries of South America, evidence for hantavirus transmission in Peru has
      been limited to the isolation of Rio Mamore virus from a pigmy mouse rat
      (Oligoryzomys microtis) in the Amazon city of Iquitos. To address the possibility
      of human hantavirus exposure in the region, we screened febrile patients
      reporting to health clinics in Iquitos from 2007 to 2010 for serological evidence
      of recent hantavirus infection. In addition, we conducted a serological survey
      for hantavirus-reactive IgG among healthy participants residing in Iquitos and
      rural areas surrounding the city. Through the febrile surveillance study, we
      identified 15 participants (0.3%; 15/5174) with IgM reactive to hantavirus (Andes
      virus) antigen, all with relatively mild, self-limited illness. From the cross
      sectional serosurvey we found that 1.7% (36/2063) of residents of the Iquitos
      area had serum IgG reactive to one or more hantaviruses, with a higher prevalence
      in the urban population (2.2%, compared to 1.1% in rural areas). These results
      suggest that human infection with hantavirus has occurred in Peru.

PMID- 22616721
TI  - Effects of pyrazole partial agonists on HCA(2) -mediated flushing and VLDL
      triglyceride levels in mice.
AB  - BACKGROUND AND PURPOSE: Niacin can effectively treat dyslipidaemic disorders.
      However, its clinical use is limited due to the cutaneous flushing mediated by
      the nicotinic acid receptor HCA(2) . In the current study, we evaluated two
      partial agonists for HCA(2) , LUF6281 and LUF6283, with respect to their anti
      dyslipidaemic potential and cutaneous flushing effect. EXPERIMENTAL APPROACH: In
      vitro potency and efficacy studies with niacin and the two HCA(2) partial
      agonists were performed using HEK293T cells stably expressing human HCA(2) .
      Normolipidaemic C57BL/6 mice received either niacin or the HCA(2) partial
      agonists (400 mg.kg(-1) .day(-1) ) once a day for 4 weeks for evaluation of their
      effects in vivo. KEY RESULTS: Radioligand competitive binding assay showed K(i)
      values for LUF6281 and LUF6283 of 3 and 0.55 uM. [(35) S]-GTPgammaS binding
      revealed the rank order of their potency as niacin > LUF6283 > LUF6281. All three
      compounds reduced plasma VLDL-triglyceride concentrations similarly, while
      LUF6281 and LUF6283, in contrast to niacin, did not also exhibit the unwanted
      flushing side effect in C57BL/6 mice. Niacin reduced the expression of lipolytic
      genes HSL and ATGL in adipose tissue by 50%, whereas LUF6281 and LUF6283
      unexpectedly did not. In contrast, the decrease in VLDL-triglyceride
      concentration induced by LUF6281 and LUF6283 was associated with a parallel >40%
      reduced expression of APOB within the liver. CONCLUSIONS AND IMPLICATIONS: The
      current study identifies LUF6281 and LUF6283, two HCA(2) partial agonists of the
      pyrazole class, as promising drug candidates to achieve the beneficial lipid
      lowering effect of niacin without producing the unwanted flushing side effect.

PMID- 22616722
TI  - Synaptic plasticity from amygdala to perirhinal cortex: a possible mechanism for
      emotional enhancement of visual recognition memory?
AB  - Emotionally salient experiences are better remembered than events that have
      little emotional context. Several lines of evidence indicate that the amygdala
      plays an important role in this emotional enhancement of memory. Visual
      recognition memory relies on synaptic plasticity in the perirhinal cortex, but
      little is known about the mechanisms involved in emotional enhancement of this
      form of memory. The results of the present study, performed in rat brain slices,
      show for the first time that the amygdala input to the perirhinal cortex
      undergoes synaptic plasticity. Stimulation in the amygdala resulted in long-term
      potentiation (LTP) in perirhinal cortex that was dependent on beta-adrenoceptors
      and L-type voltage-dependent calcium channels (L-VDCCs) but was NMDAR
      independent. In contrast, intracortical perirhinal stimulation resulted in LTP
      that was NMDAR-dependent but beta-adrenoceptor- and L-VDCC-independent. In
      addition, the present results provide the first evidence that stimulation of the
      amygdala can reduce the threshold for LTP in the perirhinal cortex.
      Interestingly, this associative form of LTP requires beta-adrenoceptor activation
      but not NMDA or L-VDCC activation. Knowing the mechanisms that control amygdala
      perirhinal cortex interactions will allow better understanding of how emotionally
      charged visual events are remembered, and may help to understand how memories can
      consolidate and become intrusive in anxiety-related disorders.

PMID- 22616723
TI  - Factors associated with higher fecundity in female maternal relatives of
      homosexual men.
AB  - INTRODUCTION: Recent evidence suggests that sexually antagonistic genetic factors
      in the maternal line promote homosexuality in men and fecundity in female
      relatives. However, it is not clear if and how these genetic factors are
      phenotypically expressed to simultaneously induce homosexuality in men and
      increased fecundity in their mothers and maternal aunts. AIMS: The aim of the
      present study was to investigate the phenotypic expression of genetic factors
      that could explain increased fecundity in the putative female carriers. METHODS:
      Using a questionnaire-based approach, which included also the Big Five
      Questionnaire personality inventory based on the Big Five theory, we investigated
      fecundity in 161 female European subjects and scrutinized possible influences,
      including physiological, behavioral, and personality factors. We compared 61
      female probands who were either mothers or maternal aunts of homosexual men. One
      hundred females who were mothers or aunts of heterosexual men were used as
      controls. MAIN OUTCOME MEASURES: Personality traits, retrospective physiological
      and clinical data, behavior and opinions on fecundity-related issues were
      assessed and analyzed to illustrate possible effects on fecundity between
      probands and control females. RESULTS: Our analysis showed that both mothers and
      maternal aunts of homosexual men show increased fecundity compared with
      corresponding maternal female relatives of heterosexual men. A two-step
      statistical analysis, which was based on t-tests and multiple logistic regression
      analysis, showed that mothers and maternal aunts of homosexual men (i) had fewer
      gynecological disorders; (ii) had fewer complicated pregnancies; (iii) had less
      interest in having children; (iv) placed less emphasis on romantic love within
      couples; (v) placed less importance on their social life; (vi) showed reduced
      family stability; (vii) were more extraverted; and (viii) had divorced or
      separated from their spouses more frequently. CONCLUSIONS: Our findings are based
      on a small sample and would benefit from a larger replication, however they
      suggest that if sexually antagonistic genetic factors that induce homosexuality
      in males exist, the factors might be maintained in the population by contributing
      to increased fecundity greater reproductive health, extraversion, and a generally
      relaxed attitude toward family and social values in females of the maternal line
      of homosexual men.

PMID- 22616725
TI  - Diversity of faecal oxalate-degrading bacteria in black and white South African
      study groups: insights into understanding the rarity of urolithiasis in the black
      group.
AB  - AIM: To examine whether enhanced diversity or numbers of oxalate-degrading
      bacteria in the gastrointestinal tracts of black South Africans play a role in
      determining the rarity of urolithiasis in this group. METHODS AND RESULTS: Fresh
      faecal samples collected from healthy black and white South African male
      volunteers were analysed in terms of bacterial oxalate-degrading activity,
      bacterial diversity and relative species abundance. Varied bacterial populations
      prepared from samples from the low-risk black group showed a significantly higher
      level of oxalate degradation. Denaturing gradient gel electrophoresis analyses of
      Lactobacillus and related spp. and Bifidobacterium spp. 16S rRNA PCR products
      revealed a significantly higher faecal Lactobacillus diversity for the low-risk
      black group relative to the higher-risk white group. Quantitative real-time PCR
      experiments did not show any significant differences between the study groups for
      Lactobacillus and related spp.. However, Bifidobacterium spp. were present at a
      significantly higher relative abundance in the black group. Oxalobacter
      formigenes was present only at very low levels in either group. CONCLUSIONS: The
      low abundance of O. formigenes and increased diversity and abundance of oxalate
      degrading Lactobacillus and Bifidobacterium spp. in the black South African
      population suggest that these strains rather than O. formigenes may protect this
      group against calcium oxalate kidney stone disease. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The South African black population harbours a pool of potential
      oxalate-degrading lactic acid bacteria, which is more abundant and diverse than
      that of white South Africans. This may be useful in developing probiotics for
      calcium oxalate kidney stone prophylaxis.

PMID- 22616724
TI  - Targeting the B cell receptor pathway in chronic lymphocytic leukemia.
AB  - The B cell receptor (BCR) pathway plays a crucial role in the survival,
      proliferation and trafficking of chronic lymphocytic leukemia (CLL) cells.
      Inhibitors of the key kinases in this pathway, including spleen tyrosine kinase
      (SYK), mammalian target of rapamycin (mTOR), phosphoinositide 3'-kinase (PI3K)
      and Bruton's tyrosine kinase (BTK), have been found in preclinical models to
      decrease CLL cell viability both directly and indirectly through modulation of
      the microenvironment. Recently, oral agents targeting each of these kinases have
      been explored in early phase clinical trials in patients with CLL. BCR pathway
      antagonists appear to be highly active in relapsed/refractory CLL, independent of
      high-risk disease markers such as del(17p). These agents have shown a unique
      pattern of inducing early transient lymphocytosis, which typically is associated
      with nodal response. Here, we review the biology of the BCR, the kinases within
      this pathway and their interaction with the CLL microenvironment. We also discuss
      data from recent and ongoing clinical trials of BCR antagonists. We address the
      development of potential biomarkers for response to these agents such as ZAP-70,
      IGHV status and CCL3, and discuss where these exciting new drugs may fit in the
      evolving landscape of CLL therapy.

PMID- 22616726
TI  - Formation of Pickering emulsions stabilized via interaction between nanoparticles
      dispersed in aqueous phase and polymer end groups dissolved in oil phase.
AB  - The influence of end groups of a polymer dissolved in an oil phase on the
      formation of a Pickering-type hydroxyapatite (HAp) nanoparticle-stabilized
      emulsion and on the morphology of HAp nanoparticle-coated microspheres prepared
      by evaporating solvent from the emulsion was investigated. Polystyrene (PS)
      molecules with varying end groups and molecular weights were used as model
      polymers. Although HAp nanoparticles alone could not function as a particulate
      emulsifier for stabilizing dichloromethane (oil) droplets, oil droplets could be
      stabilized with the aid of carboxyl end groups of the polymers dissolved in the
      oil phase. Lower-molecular-weight PS molecules containing carboxyl end groups
      formed small droplets and deflated microspheres, due to the higher concentration
      of carboxyl groups on the droplet/microsphere surface and hence stronger
      adsorption of the nanoparticles at the water/oil interface. In addition,
      Pickering-type suspension polymerization of styrene droplets stabilized by PS
      molecules containing carboxyl end groups successfully led to the formation of
      spherical HAp-coated microspheres.

PMID- 22616727
TI  - Editorial comment from Dr Ishii to recent topics related to nephrogenic systemic
      fibrosis associated with gadolinium-based contrast agents.

PMID- 22616728
TI  - Conformational Analysis of the beta-amyloid Peptide Fragment, beta(12-28).
AB  - Abstract   NMR and CD spectroscopy have been used to examine the conformation of
      the peptide, beta(12-28), (VHHQKLVFFAEDVGSNK) in aqueous and 60% TFE/40% H(2)0
      solution at pH 2.4. In 60% TFE solution, the peptide is helical as confirmed by
      the CD spectrum and by the pattern of the NOE cross peaks detected in the NOESY
      spectrum of the peptide. In aqueous solution, the peptide adopts a more extended
      and flexible conformation. Broadening of resonances at low temperature,
      temperature-dependent changes in the chemical shifts of several of the CH(alpha)
      resonances and the observation of a number of NOE contacts between the
      hydrophobic side-chain protons of the peptide are indicative of aggregation in
      aqueous solution. The behavior of beta(12-28) in 60% TFE and in aqueous solution
      are consistent with the overall conformation and aggregation behavior reported
      for the larger peptide fragment, beta(1-28) and the parent beta-amyloid peptide.

PMID- 22616731
TI  - An Invitation to Create Books and Monographs on Frontier Developments in
      Biological Structure, Dynamics, Interactions & Expression.

PMID- 22616733
TI  - What is the best DFT functional for vibronic calculations? A comparison of the
      calculated vibronic structure of the S1-S0 transition of phenylacetylene with
      cavity ringdown band intensities.
AB  - The sensitivity of vibronic calculations to electronic structure methods and
      basis sets is explored and compared to accurate relative intensities of the
      vibrational bands of phenylacetylene in the S(1)(A(1)B(2)) <- S(0)(X(1)A(1))
      transition. To provide a better measure of vibrational band intensities, the
      spectrum was recorded by cavity ringdown absorption spectroscopy up to energies
      of 2000 cm(-1) above the band origin in a slit jet sample. The sample rotational
      temperature was estimated to be about 30 K, but the vibrational temperature was
      higher, permitting the assignment of many vibrational hot bands. The vibronic
      structure of the electronic transition was simulated using a combination of time
      dependent density functional theory (TD-DFT) electronic structure codes, Franck
      Condon integral calculations, and a second-order vibronic model developed
      previously [Johnson, P. M.; Xu, H. F.; Sears, T. J. J. Chem. Phys. 2006, 125,
      164331]. The density functional theory (DFT) functionals B3LYP, CAM-B3LYP, and LC
      BLYP were explored. The long-range-corrected functionals, CAM-B3LYP and LC-BLYP,
      produced better values for the equilibrium geometry transition moment, but
      overemphasized the vibronic coupling for some normal modes, while B3LYP provided
      better-balanced vibronic coupling but a poor equilibrium transition moment.
      Enlarging the basis set made very little difference. The cavity ringdown
      measurements show that earlier intensities derived from resonance-enhanced
      multiphoton ionization (REMPI) spectra have relative intensity errors.

PMID- 22616734
TI  - Enhancement of intrinsic emission from ultrathin ZnO films using Si nanopillar
      template.
AB  - Highly efficient room-temperature ultraviolet (UV) luminescence is obtained in
      heterostructures consisting of 10-nm-thick ultrathin ZnO films grown on Si
      nanopillars fabricated using self-assembled silver nanoislands as a natural metal
      nanomask during a subsequent dry etching process. Atomic layer deposition was
      applied for depositing the ZnO films on the Si nanopillars under an ambient
      temperature of 200 degrees C. Based on measurements of photoluminescence (PL), an
      intensive UV emission corresponding to free-exciton recombination (approximately
      3.31 eV) was observed with a nearly complete suppression of the defect
      associated, broad-range visible emission peak. As compared to the ZnO/Si
      substrate, the almost five-times-of-magnitude enhancement in the intensity of PL,
      which peaked around 3.31 eV in the present ultrathin ZnO/Si nanopillars, is
      presumably attributed to the high surface/volume ratio inherent to the Si
      nanopillars. This allowed considerably more amount of ZnO material to be grown on
      the template and led to markedly more efficient intrinsic emission.

PMID- 22616735
TI  - Increased behavioural responsiveness with complex stimulation in VS and MCS:
      preliminary results.
AB  - PRIMARY OBJECTIVE: Even in non-communicative disorders of consciousness such as
      vegetative and minimally conscious states, increasing the personal relevance and
      complexity of stimuli appears to enhance their activating effect in patients. It
      was hypothesized that enriched stimulation in an immersive environment could
      increase the number and/or the goal-directed quality of active movements.
      METHODS, RESEARCH DESIGN AND PROCEDURES: Twelve patients with severe disorders of
      consciousness in the post-acute phase underwent an experimental protocol of
      sensory stimulation based on biographically meaningful objects. Enriched
      stimulation was compared to both a pattern of stimulation without augmented
      context and to standard interactions in a clinical setting. An A-B-C-B-A paradigm
      was applied to minimize the confounding effects of clinical changes during the
      protocol. The motor behaviours were recorded using the Wessex Head Injury Matrix
      (WHIM) and analysed with standard parametric statistics. RESULTS AND CONCLUSIONS:
      The results show a difference in patient response as a function of stimulation
      context: familiar objects in an augmented environment elicited a greater range of
      behavioural responses. These results support the hypothesis that the emotional
      richness and complexity of environmental stimuli can play a key role in evoking
      active behaviours.

PMID- 22616736
TI  - Microparticles, not only markers but also a therapeutic target in the early stage
      of diabetic retinopathy and vascular aging.
AB  - INTRODUCTION: Microparticles (MPs) are small vesicles between 100 and 500 nm,
      released from different cells including blood, endothelium, smooth muscle, and
      retina cells. MPs are produced during shedding process in response to some
      stressing and stimulating factors, as well as during apoptosis. The cellular
      machinery leading to MP shedding involves the loss of the plasma membrane
      asymmetry and phosphatidylserine externalization with an increase in cytosolic
      calcium concentrations. MPs not only transfer membrane proteins from the cells of
      their origin but also convey phospholipids and microRNA to the distant cells.
      Some of these macromolecules have neoangiogenetic properties (factor XII, tissue
      factor or mitogen-activated protein kinases) or participate in modulation of
      vascular senescence or remodeling (miRNAs). AREAS COVERED: The authors summarise
      recent knowledge about MP biology and pathophysiology. The mechanisms involved in
      MP release are discussed, and special emphasis is placed on clinical studies,
      which document their proangiogenic role in diabetic retinopathy and vascular
      aging. EXPERT OPINION: The pharmacological control of phospholipid moieties in
      the plasma membrane and the regulation of the MP shedding remains a challenge in
      the early stage of diabetic retinopathy and vascular aging.

PMID- 22616737
TI  - Exfoliation of non-oxidized graphene flakes for scalable conductive film.
AB  - The increasing demand for graphene has required a new route for its mass
      production without causing extreme damages. Here we demonstrate a simple and cost
      effective intercalation based exfoliation method for preparing high quality
      graphene flakes, which form a stable dispersion in organic solvents without any
      functionalization and surfactant. Successful intercalation of alkali metal
      between graphite interlayers through liquid-state diffusion from ternary KCl-NaCl
      ZnCl(2) eutectic system is confirmed by X-ray diffraction and X-ray photoelectric
      spectroscopy. Chemical composition and morphology analyses prove that the
      graphene flakes preserve their intrinsic properties without any degradation. The
      graphene flakes remain dispersed in a mixture of pyridine and salts for more than
      6 months. We apply these results to produce transparent conducting (~930 Omega/?
      at ~75% transmission) graphene films using the modified Langmuir-Blodgett method.
      The overall results suggest that our method can be a scalable (>1 g/batch) and
      economical route for the synthesis of nonoxidized graphene flakes.

PMID- 22616738
TI  - Nipple inversion caused by a breast leiomyoma.

PMID- 22616739
TI  - A contrast in safety, pharmacokinetics and pharmacodynamics across age groups
      after a single 50 mg oral dose of the gamma-secretase inhibitor avagacestat.
AB  - AIM: To evaluate the single dose pharmacokinetics, pharmacodynamics, and
      preliminary tolerability of the gamma-secretase inhibitor BMS-708163
      (avagacestat) in young and elderly men and women. METHODS: All subjects received
      double-blinded administration of a single 50 mg dose of avagacestat in capsule
      form or matching placebo. Main evaluations included pharmacokinetics, safety,
      plasma amyloid-beta (Abeta)(1-40) concentratios and exploration of Notch
      biomarkers. RESULTS: Avagacestat 50 mg capsule was well tolerated and rapidly
      absorbed among young and elderly subjects, with a median t(max) between 1 and 2 h
      post dose and an average half-life between 41 and 71 h. In general, subjects aged
      75 years or more had higher AUC(0,infinity) values than those aged less than 75
      years. An exploratory analysis of Abeta(1-40) serum concentrations showed a
      pattern of decreasing concentrations over the first 4-6 h followed by a rise
      above baseline that was maintained until the end of the assessment period.
      Adverse events were generally mild, occurring more frequently in elderly
      subjects, with no observed difference between subjects receiving avagacestat and
      placebo. No dose limiting gastrointestinal effects of avagacestat were observed
      and exploratory biomarkers of Notch inhibition did not change significantly.
      CONCLUSIONS: The favourable safety profile and pharmacokinetic effects of
      avagacestat in this study support its continued development, especially in the
      target population of elderly subjects with mild cognitive impairment or
      Alzheimer's disease.

PMID- 22616740
TI  - Cytologic features of clear cell adnexal carcinoma in 3 dogs.
AB  - BACKGROUND: Clear cell adnexal carcinoma is a rare cutaneous adnexal neoplasm
      without definitive apocrine, sebaceous, or follicular differentiation.
      Differential diagnoses include sebaceous carcinoma, liposarcoma, and balloon cell
      melanoma. Immunohistochemical analysis, with positive immunoreactivity for
      pancytokeratin and vimentin, aids in the diagnosis. Cytologic features of clear
      cell adnexal carcinoma have not been described previously. OBJECTIVE: The aim of
      this study was to describe cytologic features of canine clear cell adnexal
      carcinoma. METHODS: Fine-needle aspirates (FNA) obtained prior to biopsy of
      cutaneous neoplasms with a histologic diagnosis of clear cell adnexal carcinoma
      confirmed by immunohistochemical analysis were reviewed retrospectively. Slides
      prepared from FNA had been stained with modified Wright-Giemsa or automated
      aqueous Romanowsky stain. RESULTS: Of 20 neoplasms diagnosed as clear cell
      adnexal carcinoma in dogs, FNA of the mass had been performed in 3 cases.
      Cytologic features were similar and included high cellularity, marked cellular
      pleomorphism, loose arrangement of neoplastic cells, and a light blue to gray
      background resulting from streaming of cytoplasm from ruptured cells. Neoplastic
      cells were oval to polygonal to spindle-shaped with wispy cytoplasmic
      projections. Cytoplasmic eosinophilic stippling, globular deposits, or pink
      needle-shaped inclusions were noted. Criteria of malignancy included marked
      anisocytosis, anisokaryosis and anisonucleoleosis, multinucleation, karyomegaly,
      macronucleoli, and atypical mitotic figures. CONCLUSIONS: Clear cell adnexal
      carcinoma should be included in the cytologic differential diagnosis for a canine
      cutaneous mass even if an epithelial origin is not readily identified owing to
      lack of characteristic epithelial features, such as highly cohesive cell
      clusters, evident cell-to-cell junctions, and distinct cytoplasmic edges.

PMID- 22616741
TI  - Hydrogen storage materials discovery via high throughput ball milling and gas
      sorption.
AB  - The lack of a high capacity hydrogen storage material is a major barrier to the
      implementation of the hydrogen economy. To accelerate discovery of such
      materials, we have developed a high-throughput workflow for screening of hydrogen
      storage materials in which candidate materials are synthesized and characterized
      via highly parallel ball mills and volumetric gas sorption instruments,
      respectively. The workflow was used to identify mixed imides with significantly
      enhanced absorption rates relative to Li2Mg(NH)2. The most promising material,
      2LiNH2:MgH2 + 5 atom % LiBH4 + 0.5 atom % La, exhibits the best balance of
      absorption rate, capacity, and cycle-life, absorbing >4 wt % H2 in 1 h at 120 
      degrees C after 11 absorption-desorption cycles. 

PMID- 22616743
TI  - Etanercept does not impair healing in rat models of tendon or metaphyseal bone
      injury.
AB  - BACKGROUND AND PURPOSE: Should blockade of TNF-alpha be avoided after orthopedic
      surgery? Healing of injuries in soft tissues and bone starts with a brief
      inflammatory phase. Modulation of inflammatory signaling might therefore
      interfere with healing. For example, Cox inhibitors impair healing in animal
      models of tendon, ligament, and bone injury, as well as in fracture patients. TNF
      alpha is expressed locally at increased levels during early healing of these
      tissues. We therefore investigated whether blocking of TNF-alpha with etanercept
      influences the healing process in established rat models of injury of tendons and
      metaphyseal bone. METHODS: Rats were injected with etanercept, 3.5 mg/kg 3 times
      a week. Healing of transected Achilles tendons and bone healing around screws
      implanted in the tibial metaphysis were estimated by mechanical testing. Tendons
      were allowed to heal either with or without mechanical loading. Ectopic bone
      induction following intramuscular BMP-2 implants has previously been shown to be
      stimulated by etanercept in rodents. This was now tested as a positive control.
      RESULTS: Tendon peak force after 10 days was not significantly influenced by
      etanercept. Changes exceeding 29% could be excluded with 95% confidence.
      Likewise, screw pull-out force was not significantly influenced. More than 25%
      decrease or 18% increase could be excluded with 95% confidence. However,
      etanercept treatment increased the amount of bone induced by intramuscular BMP-2
      implants, as estimated by blind histological scoring. INTERPRETATION: Etanercept
      does not appear to impair tendon or metaphyseal bone healing to any substantial
      degree.

PMID- 22616742
TI  - PCR-hybridization after sonication improves diagnosis of implant-related
      infection.
AB  - PURPOSE: We wanted to improve the diagnosis of implant-related infection using
      molecular biological techniques after sonication. METHODS: We studied 258
      retrieved implant components (185 prosthetic implants and 73 osteosynthesis
      implants) from 126 patients. 47 patients had a clinical diagnosis of infection
      (108 components) and 79 patients did not (150 components). The fluids from
      sonication of retrieved implants were tested in culture and were also analyzed
      using a modified commercial PCR kit for detection of Gram-positive and Gram
      negative bacteria (GenoType BC; Hain Lifescience) after extraction of the DNA.
      RESULTS: 38 of 47 patients with a clinical diagnosis of infection were also
      diagnosed as being infected using culture and/or PCR (35 by culture alone). Also,
      24 patients of the 79 cases with no clinical diagnosis of infection were
      identified microbiologically as being infected (4 by culture, 16 by PCR, and 4 by
      both culture and PCR). Comparing culture and PCR, positive culture results were
      obtained in 28 of the 79 patients and positive PCR results were obtained in 35.
      There were 21 discordant results in patients who were originally clinically
      diagnosed as being infected and 28 discordant results in patients who had no
      clinical diagnosis of infection. INTERPRETATION: For prosthetic joint infections
      and relative to culture, molecular detection can increase (by one tenth) the
      number of patients diagnosed as having an infection. Positive results from
      patients who have no clinical diagnosis of infection must be interpreted
      carefully.

PMID- 22616744
TI  - Outcome of repaired unstable meniscal tears in children and adolescents.
AB  - BACKGROUND: Unstable meniscal tears are rare injuries in skeletally immature
      patients. Loss of a meniscus increases the risk of subsequent development of
      degenerative changes in the knee. This study deals with the outcome of
      intraarticular meniscal repair and factors that affect healing. Parameters of
      interest were type and location of the tear and also the influence of
      simultaneous reconstruction of a ruptured ACL. METHODS: We investigated the
      outcome of 25 patients (29 menisci) aged 15 (4-17) years who underwent surgery
      for full thickness meniscal tears, either as isolated lesions or in combination
      with ACL ruptures. Intraoperative documentation followed the IKDC 2000 standard.
      Outcome measurements were the Tegner score (pre- and postoperatively) and the
      Lysholm score (postoperatively) after an average follow-up period of 2.3 years,
      with postoperative arthroscopy and MRT in some cases. RESULTS: 24 of the 29
      meniscal lesions healed (defined as giving an asymptomatic patient) regardless of
      location or type. 4 patients re-ruptured their menisci (all in the pars
      intermedia) at an average of 15 months after surgery following a new injury. Mean
      Lysholm score at follow-up was 95, the Tegner score deteriorated, mean
      preoperative score: 7.8 (4-10); mean postoperative score: 7.2 (4-10). Patients
      with simultaneous ACL reconstruction had a better outcome. INTERPRETATION: All
      meniscal tears in the skeletally immature patient are amenable to repair. All
      recurrent meniscal tears in our patients were located in the pars intermedia; the
      poorer blood supply in this region may give a higher risk of re-rupture.
      Simultaneous ACL reconstruction appears to benefit the results of meniscal
      repair.

PMID- 22616745
TI  - Hip resurfacing arthroplasty: short-term survivorship of 4,401 hips from the
      Finnish Arthroplasty Register.
AB  - BACKGROUND AND PURPOSE: Population-based registry data from the Nordic
      Arthroplasty Register Association (NARA) and from the National Joint Register of
      England and Wales have revealed that the outcome after hip resurfacing
      arthroplasty (HRA) is inferior to that of conventional total hip arthroplasty
      (THA). We analyzed the short-term survival of 4,401 HRAs in the Finnish
      Arthroplasty Register. METHODS: We compared the revision risk of the 4,401 HRAs
      from the Register to that of 48,409 THAs performed during the same time period.
      The median follow-up time was 3.5 (0-9) years for HRAs and 3.9 (0-9) years for
      THAs. RESULTS: There was no statistically significant difference in revision risk
      between HRAs and THAs (RR = 0.93, 95% CI: 0.78-1.10). Female patients had about
      double the revision risk of male patients (RR = 2.0, CI: 1.4-2.7). Hospitals that
      had performed 100 or more HRA procedures had a lower revision risk than those
      with less than 100 HRAs (RR = 0.6, CI: 0.4-0.9). Articular Surface Replacement
      (ASR, DePuy) had inferior outcome with higher revision risk than the Birmingham
      Hip Resurfacing implant (BHR, Smith & Nephew), the reference implant (RR = 1.8,
      CI: 1.2-2.7). INTERPRETATION: We found that HRA had comparable short-term
      survivorship to THA at a nationwide level. Implant design had an influence on
      revision rates. ASR had higher revision risk. Low hospital procedure volume
      worsened the outcome of HRA. Female patients had twice the revision risk of male
      patients.

PMID- 22616746
TI  - Good results with the Ponseti method: a multicenter study of 162 clubfeet
      followed for 2-5 years.
AB  - BACKGROUND AND PURPOSE: In 2002-2003, several hospitals in Norway introduced the
      Ponseti method for treating clubfoot. The present multicenter study was conducted
      to evaluate the initial results of this method, and to compare them to the good
      results reported in the literature. PATIENTS AND METHODS: 116 children with 162
      congenital idiopathic clubfeet who were born between 2004 and 2006 were treated
      with the Ponseti method at 8 hospitals in Norway. All children were prospectively
      registered at birth, and 116 feet were assessed according to Pirani before
      treatment was started. 63% used a standard bilateral foot abduction brace, and
      32% used a unilateral above-the-knee brace. One of the authors examined all feet
      at a mean age of 4 years. At follow-up, all feet were assessed by Pirani's
      scoring system, and range of motion of the foot and ankle was measured. RESULTS:
      At follow-up, 77% of the feet had a Pirani score of 0.5 or better, good
      dorsiflexion and external rotation, and no forefoot adduction. An Achilles
      tenotomy had been performed in 79% of the feet. Compliance to any brace was good;
      only 7% were defined as non-compliant. Extensive soft tissue release had been
      performed in 3% of the feet. We found no statistically significant differences
      between the two braces, except a tendency of better Pirani score in the group
      using the bilateral foot abduction brace, and a tendency of better compliance in
      patients using the unilateral brace. Better Pirani scores were found in children
      who were treated at the largest hospitals. INTERPRETATION: After introducing the
      Ponseti method in Norway, the clinical outcome was good and in accordance with
      the reports from single centers. Only 5 feet needed extensive surgery during the
      first 4 years of life.

PMID- 22616747
TI  - Microfabricated gas chromatograph for on-site determinations of TCE in indoor air
      arising from vapor intrusion. 2. Spatial/temporal monitoring.
AB  - We demonstrate the use of two prototype Si-microfabricated gas chromatographs
      (MUGC) for continuous, short-term measurements of indoor trichloroethylene (TCE)
      vapor concentrations related to the investigation of TCE vapor intrusion (VI) in
      two houses. In the first house, with documented TCE VI, temporal variations in
      TCE air concentrations were monitored continuously for up to 48 h near the
      primary VI entry location under different levels of induced differential pressure
      (relative to the subslab). Concentrations ranged from 0.23 to 27 ppb by volume
      (1.2-150 MUg/m(3)), and concentration trends agreed closely with those determined
      from concurrent reference samples. The sensitivity and temporal resolution of the
      measurements were sufficiently high to detect transient fluctuations in
      concentration resulting from short-term changes in variables affecting the extent
      of VI. Spatial monitoring showed a decreasing TCE concentration gradient with
      increasing distance from the primary VI entry location. In the second house, with
      no TCE VI, spatial profiles derived from the MUGC prototype data revealed an
      intentionally hidden source of TCE within a closet, demonstrating the capability
      for locating non-VI sources. Concentrations measured in this house ranged from
      0.51 to 56 ppb (2.7-300 MUg/m(3)), in good agreement with reference method
      values. This first field demonstration of MUGC technology for automated, near
      real-time, selective VOC monitoring at low- or subppb levels augurs well for its
      use in short- and long-term on-site analysis of indoor air in support of VI
      assessments.

PMID- 22616748
TI  - Evidence of mosquito-transmitted flavivirus circulation in Piedmont, north
      western Italy.
AB  - BACKGROUND: Flavivirus is a highly heterogeneous viral genus that includes
      important human pathogens and several viral strains with unknown zoonotic
      potential. Mosquito-borne flaviviruses have been isolated and characterized in
      Northern Italy: West Nile virus and Usutu virus were detected in mosquitoes and
      in different host species and recent studies provided evidence about the
      circulation of "insect Flavivirus" strains. METHODS: In order to clarify the
      diffusion and the distribution of the mosquito-transmitted flaviviruses in Italy,
      we analyzed Culex and Ochlerotatus mosquitoes collected in 2009 and 2010 in an
      area divided evenly between hills and plains and where the landscape is dominated
      by mixed agricultural patches, rice fields, deciduous tree forests, and urban
      environments. Each mosquito pool was tested for the presence of Flavivirus
      strains and we characterized positive samples by genetic sequencing. RESULTS:
      Positive mosquito pools revealed low infection prevalence, but suggested a
      continuous circulation of both Usutu virus and insect Flavivirus. Interestingly,
      phylogenetic analyses based on NS5 gene partial sequences showed a closer
      relationship among new Usutu virus strains from Piedmont and the reference
      sequences from the Eastern Europe, with respect to Italian samples characterized
      so far. Moreover, NS5 gene phylogeny suggested that mosquito flaviviruses found
      in Italy could belong to different lineages. CONCLUSIONS: Our results contribute
      to a wider point of view on the heterogeneity of viruses infecting mosquitoes
      suggesting a taxonomical revision of the Mosquito-borne Flavivirus group.

PMID- 22616749
TI  - Unimanual and bimanual continuous movements benefit from visual instructions in
      persons with Down syndrome.
AB  - The authors' aim was to understand how persons with Down syndrome (DS) perform
      different tasks and to assess if there were any differences in performance based
      on the type of instructions. This is important because of neurological
      differences in persons with DS and neurological demands for performing different
      types of tasks. Twenty right-handed participants with DS, 20 chronological age
      matched (CA), and 20 mental age-matched (MA) performed unimanual, bimanual,
      discrete, and continuous drumming following visual, auditory, and verbal
      instructions. Overall, discrete drumming was performed with shorter movement
      times than continuous drumming and unimanual drumming was performed with shorter
      movement amplitude than bimanual drumming. With respect to instructions, persons
      with DS performed with smaller amplitudes, thus more efficient movements,
      following the visual instructions than auditory and verbal instructions for all
      types of tasks, whereas CA performed similarly with all instructions and MA
      performed with smaller amplitudes with visual instructions than auditory
      instructions. These results suggest that visual instruction provides the best
      information for people with DS to aid in performance of many different types of
      movements.

PMID- 22616750
TI  - The role of low testosterone associated with erectile dysfunction with atopic
      dermatitis.

PMID- 22616751
TI  - GABA transporter subtype 1 and GABA transporter subtype 3 modulate glutamatergic
      transmission via activation of presynaptic GABA(B)  receptors in the rat globus
      pallidus.
AB  - The intra-pallidal application of gamma-aminobutyric acid (GABA) transporter
      subtype 1 (GAT-1) or GABA transporter subtype 3 (GAT-3) transporter blockers [1
      (4,4-diphenyl-3-butenyl)-3-piperidinecarboxylic acid hydrochloride (SKF 89976A)
      or 1-[2-[tris(4-methoxyphenyl)methoxy]ethyl]-(S)-3-piperidinecarboxylic acid
      (SNAP 5114)] reduces the activity of pallidal neurons in monkey. This effect
      could be mediated through the activation of presynaptic GABA(B) heteroreceptors
      in glutamatergic terminals by GABA spillover following GABA transporter (GAT)
      blockade. To test this hypothesis, we applied the whole-cell recording technique
      to study the effects of SKF 89976A and SNAP 5114 on evoked excitatory
      postsynaptic currents (eEPSCs) in the presence of gabazine, a GABA(A) receptor
      antagonist, in rat globus pallidus slice preparations. Under the condition of
      postsynaptic GABA(B) receptor blockade by the intra-cellular application of N
      (2,6-dimethylphenylcarbamoylmethyl)-triethylammonium bromide (OX314), bath
      application of SKF 89976A (10 MUM) or SNAP 5114 (10 MUM) decreased the amplitude
      of eEPSCs, without a significant effect on its holding current and whole cell
      input resistance. The inhibitory effect of GAT blockade on eEPSCs was blocked by
      (2S)-3-[[(1S)-1-(3,4-dichlorophenyl)ethyl]amino-2
      hydroxypropyl](phenylmethyl)phosphinic acid, a GABA(B) receptor antagonist. The
      paired-pulse ratio of eEPSCs was increased, whereas the frequency, but not the
      amplitude, of miniature excitatory postsynaptic currents was reduced in the
      presence of either GAT blocker, demonstrating a presynaptic effect. These results
      suggest that synaptically released GABA can inhibit glutamatergic transmission
      through the activation of presynaptic GABA(B) heteroreceptors following GAT-1 or
      GAT-3 blockade. In conclusion, our findings demonstrate that presynaptic GABA(B)
      heteroreceptors in putative glutamatergic subthalamic afferents to the globus
      pallidus are sensitive to increases in extracellular GABA induced by GAT
      inactivation, thereby suggesting that GAT blockade represents a potential
      mechanism by which overactive subthalamopallidal activity may be reduced in
      parkinsonism.

PMID- 22616752
TI  - Can small non-peptide motilin agonists force a breakthrough as gastroprokinetic
      drugs?
AB  - GSK962040 is a small selective motilin receptor agonist currently under
      investigation in clinical trials for the treatment of conditions associated with
      delayed gastric emptying. As reported in this issue of the British Journal of
      Pharmacology, Broad et al., studied for the first time the region-dependent
      contractile effects of motilin and GSK962040 in human smooth muscle strips. Both
      compounds facilitated cholinergically mediated contractions of human gastric
      antral muscle strips at low concentrations and induced smooth muscle contractions
      at high concentrations. The effect was less pronounced in the fundus and almost
      absent in the colon. The long-lasting facilitation of cholinergic responses in
      the antrum by GSK962040 compared with the fading responses to motilin may be of
      importance from a clinical point of view. The approach used by Broad et al. with
      human tissue is a validated model to identify motilin receptor agonists with
      therapeutic value.

PMID- 22616753
TI  - Chronic myeloid leukemia stem cells display alterations in expression of genes
      involved in oxidative phosphorylation.
AB  - The mitochondrial respiratory chain (MRC) consists of protein complexes I, II,
      III, IV and V that support oxidative phosphorylation (OXPHOS), which depends on
      electron transport to generate adenosine triphosphate (ATP). Electron "leakage"
      from the MRC generates reactive oxygen species (ROS). Chronic myeloid leukemia in
      chronic phase (CML-CP) stem cells (LSCs) produce high levels of mitochondrial
      ROS, causing oxidative DNA damage, resulting in genomic instability, generating
      imatinib-resistant BCR-ABL1 kinase mutants and additional chromosomal
      aberrations. Using global mRNA microarray analysis combined with Ingenuity
      Pathway Analysis we found that LSCs display enhanced expression of genes encoding
      MRC complexes I, II, IV and V. However, expression of genes encoding complex III
      was deregulated. Treatment with imatinib did not correct the aberrant levels of
      MRC genes. Therefore we postulate that abnormal expression of MRC genes may
      facilitate electron "leakage" to promote the production of ROS and accumulation
      of genomic instability in LSCs in imatinib-naive and imatinib-treated patients.

PMID- 22616754
TI  - Total synthesis of Akuammiline alkaloid (-)-vincorine via intramolecular
      oxidative coupling.
AB  - An asymmetric total synthesis of the  Akuammiline  alkaloid (-)-vincorine (18
      steps from 5-methoxytryptamine, 5% overall yield) is described. The key steps
      include Pd-catalyzed direct C-H functionalization of indole derivatives,
      organocatalyzed asymmetric Michael addition of aldehydes to alkylidene malonates,
      and intramolecular oxidative coupling between indole and malonate moieties.

PMID- 22616755
TI  - Editorial comment from Dr Mori to recent topics related to nephrogenic systemic
      fibrosis associated with gadolinium-based contrast agents.

PMID- 22616756
TI  - A comparison of the antifouling/foul-release characteristics of non-biocidal
      xerogel and commercial coatings toward micro- and macrofouling organisms.
AB  - Five non-biocidal xerogel coatings were compared to two commercial non-biocidal
      coatings and a silicone standard with respect to antifouling (AF)/fouling-release
      (FR) characteristics. The formation and release of biofilm of the marine
      bacterium Cellulophaga lytica, the attachment and release of the microalga
      Navicula incerta, and the fraction removal and critical removal stress of
      reattached adult barnacles of Amphibalanus amphitrite were evaluated in
      laboratory assays. Correlations of AF/FR performance with surface characteristics
      such as wettability, surface energy, elastic modulus, and surface roughness were
      examined. Several of the xerogel coating compositions performed well against both
      microfouling organisms while the commercial coatings performed less well toward
      the removal of microalgae. Reattached barnacle adhesion as measured by critical
      removal stress was significantly lower on the commercial coatings when compared
      to the xerogel coatings. However, two xerogel compositions showed release of 89
      100% of reattached barnacles. These two formulations were also tested in the
      field and showed similar results.

PMID- 22616758
TI  - An unexpected silver triflate catalyzed reaction of 2-alkynylbenzaldehyde with 2
      isocyanoacetate.
AB  - An unexpected silver triflate catalyzed reaction of 2-alkynylbenzaldehyde with 2
      isocyanoacetate provides an efficient route for the generation of isoquinolines.
      The reaction proceeds smoothly in air under mild conditions with high efficiency.

PMID- 22616757
TI  - Patterning of antibodies using flexographic printing.
AB  - Antibodies were patterned onto flexible plastic films using the flexographic
      printing process. An ink formulation was developed using high molecular weight
      polyvinyl alcohol in carbonate-bicarbonate buffer. In order to aid both antibody
      adhesion and the quality of definition in the printed features, a nitrocellulose
      coating was developed that was capable of being discretely patterned, thus
      increasing the signal-to-noise ratio of an antibody array. Printing antibody
      features such as dots, squares, text, and fine lines were reproduced effectively.
      Furthermore, this process could be easily adapted for printing of other
      biological materials, including, but not limited to, enzymes, DNA, proteins,
      aptamers, and cells.

PMID- 22616759
TI  - Relation between electrical properties of aerosol-deposited BaTiO3 thin films and
      their mechanical hardness measured by nano-indentation.
AB  - To achieve a high capacitance density for embedded decoupling capacitor
      applications, the aerosol deposition (AD) process was applied as a thin film
      deposition process. BaTiO3 films were fabricated on Cu substrates by the AD
      process at room temperature, and the film thickness was reduced to confirm the
      limit of the critical minimum thickness for dielectric properties. As a result,
      the BaTiO3 thin films that were less than 1-MUm thick showed unstable electric
      properties owing to their high leakage currents. Therefore, to overcome this
      problem, the causes of the high leakage currents were investigated. In this
      study, it was confirmed that by comparing BaTiO3 thin films on Cu substrates with
      those on stainless steels (SUS) substrates, macroscopic defects and rough
      interfaces between films and substrates influence the leakage currents. Moreover,
      based on the deposition mechanism of the AD process, it was considered that the
      BaTiO3 thin films on Cu substrates with thicknesses of less than 1 MUm are formed
      with chinks and weak particle-to-particle bonding, giving rise to leakage
      currents. In order to confirm the relation between the above-mentioned surface
      morphologies and the dielectric behavior, the hardness of BaTiO3 films on Cu and
      SUS substrates was investigated by nano-indentation. Consequently, we proposed
      that the chinks and weak particle-to-particle bonding in the BaTiO3 thin films
      with thicknesses of less than 0.5 MUm on Cu substrates could be the main cause of
      the high leakage currents.

PMID- 22616760
TI  - Aesthetic analysis of an implant-supported denture at the cleft area.
AB  - Objective : To evaluate the aesthetics of an implant-supported denture at the
      cleft area, comparing the peri-implant tissues and prosthetic crown with the
      contralateral tooth. Settings : Hospital for Rehabilitation of Craniofacial
      Anomalies, Bauru, Sao Paolo, Brazil. Patients : A total of 39 individuals of both
      genders, with complete unilateral cleft lip and palate, who received secondary
      alveolar bone graft and were rehabilitated with single implant-supported dentures
      at the area of the missing maxillary lateral incisor after completion of
      orthodontic treatment. Interventions : The following parameters were analyzed in
      follow-up sessions: length and width of prosthetic crown and contralateral tooth,
      characteristics of implants, filling of interproximal space by the papilla, and
      smile height of the patients. Results : The implant-supported prosthetic crowns
      were longer than the contralateral tooth (p < .001). Among the 78 papillae
      analyzed, 29 (37.17%) received a score of 3; 32 (41.02%) papillae had a score of
      2; and 17 (21.79%) received a score of 1. Concerning the smile height, among the
      39 patients analyzed, 23 (56.41%) had a medium smile, 15 (38.46%) had a high
      smile, and two (5.12%) presented a low smile. Conclusion : The use of dental
      implants to rehabilitate the edentulous cleft area is an excellent option.
      However, adequate evaluation of the bone quantity and quality, positioning and
      shape of adjacent teeth, smile height, and patient expectations should be
      considered to achieve success and avoid aesthetic deformities such as elongated
      teeth and absence of gingival papillae. 

PMID- 22616761
TI  - The implications of patients and carers as active agents in health care and the
      consequences for their own health, the health of their families and health
      system.

PMID- 22616763
TI  - Accurate prediction of cation-pi interaction energy using substituent effects.
AB  - Substituent effects on cation-pi interactions have been quantified using a
      variety of Phi-X...M(+) complexes where Phi, X, and M(+) are the pi-system,
      substituent, and cation, respectively. The cation-pi interaction energy, E(M(+)),
      showed a strong linear correlation with the molecular electrostatic potential
      (MESP) based measure of the substituent effect, DeltaV(min) (the difference
      between the MESP minimum (V(min)) on the pi-region of a substituted system and
      the corresponding unsubstituted system). This linear relationship is E(M(+)) =
      C(M(+))(DeltaV(min)) + E(M(+))' where C(M(+)) is the reaction constant and
      E(M(+))' is the cation-pi interaction energy of the unsubstituted complex. This
      relationship is similar to the Hammett equation and its first term yields the
      substituent contribution of the cation-pi interaction energy. Further, a linear
      correlation between C(M(+))() and E(M(+))()' has been established, which
      facilitates the prediction of C(M(+)) for unknown cations. Thus, a prediction of
      E(M(+)) for any Phi-X...M(+) complex is achieved by knowing the values of
      E(M(+))' and DeltaV(min). The generality of the equation is tested for a variety
      of cations (Li(+), Na(+), K(+), Mg(+), BeCl(+), MgCl(+), CaCl(+), TiCl(3)(+),
      CrCl(2)(+), NiCl(+), Cu(+), ZnCl(+), NH(4)(+), CH(3)NH(3)(+), N(CH(3))(4)(+),
      C(NH(2))(3)(+)), substituents (N(CH(3))(2), NH(2), OCH(3), CH(3), OH, H, SCH(3),
      SH, CCH, F, Cl, COOH, CHO, CF(3), CN, NO(2)), and a large number of pi-systems.
      The tested systems also include multiple substituted pi-systems, viz. ethylene,
      acetylene, hexa-1,3,5-triene, benzene, naphthalene, indole, pyrrole,
      phenylalanine, tryptophan, tyrosine, azulene, pyrene, [6]-cyclacene, and
      corannulene and found that E(M)(+) follows the additivity of substituent effects.
      Further, the substituent effects on cationic sandwich complexes of the type
      C(6)H(6)...M(+)...C(6)H(5)X have been assessed and found that E(M(+)) can be
      predicted with 97.7% accuracy using the values of E(M(+))' and DeltaV(min). All
      the Phi-X...M(+) systems showed good agreement between the calculated and
      predicted E(M(+))() values, suggesting that the DeltaV(min) approach to
      substituent effect is accurate and useful for predicting the interactive behavior
      of substituted pi-systems with cations.

PMID- 22616762
TI  - Pharmacokinetics and tolerability of SRT2104, a first-in-class small molecule
      activator of SIRT1, after single and repeated oral administration in man.
AB  - AIM: SRT2104 is a novel, first-in-class, highly selective small molecule
      activator of the NAD + dependent deacetylase SIRT1. SRT2104 was dosed to healthy
      male and female volunteers in a series of phase 1 clinical studies that were
      designed to elucidate tolerability and pharmacokinetics associated with oral
      dosing to aid in dose selection for subsequent clinical trials. METHODS: In the
      first-in-human study, there was both a single dose phase and 7 day repeat dose
      phase. Doses used ranged from 0.03 to 3.0 g. A radioactive microtracer study was
      subsequently conducted to determine systemic clearance, bioavailability and
      preliminary metabolism, and a crossover study was conducted to determine the
      effect of gender, formulation and feeding state on SRT2104 pharmacokinetics.
      RESULTS: SRT2104 was well tolerated in all of these studies, with no serious
      adverse reactions observed. SRT2104 displayed a dose-dependent, but sub
      proportional increase in exposure following single dose and repeated dose
      administration. Accumulation of three-fold or less occurs after 7 days of repeat
      dosing. The mean bioavailability was circa 14% and the mean clearance was circa
      400 ml min(-1). Although there were no substantial effects on exposure resulting
      from gender or formulation differences, a notable food effect was observed,
      manifested as up to four-fold increase in exposure parameters. CONCLUSIONS: In
      the absence of an optimized formulation of SRT2104, the food effect can be used
      to maximize exposure in future clinical studies. Combined with the good
      tolerability of all doses demonstrated in these studies, the favourable
      selectivity profile of SRT2104 allows for the use of this SIRT1 modulator for
      target validation in the clinic.

PMID- 22616764
TI  - Do brain activation changes persist in athletes with a history of multiple
      concussions who are asymptomatic?
AB  - PRIMARY OBJECTIVE: To evaluate brain activation patterns of asymptomatic athletes
      with a history of two or more concussions. RESEARCH DESIGN: A paired case-control
      design was used to evaluate brain activation patterns during cognitive
      performance in 14 athletes with a history of two or more concussions and 14 age-
      and sex-matched controls with no previous concussion. METHODS AND PROCEDURES:
      Percentage Blood-Oxygen-Level-Dependent (BOLD) change during an N-back working
      memory task was assessed in all participants. Performance on the Trail-Making
      Test Form A and B, Symbol-Digit Modalities Test and the Immediate Post-concussion
      Assessment and Cognitive Test (ImPACT) was also compared between groups. MAIN
      RESULTS: As expected, brain regions activated during the performance of the N
      back were equivalent between groups. The groups performed similarly on the
      neurocognitive measures. The history of concussion group was less accurate than
      controls on the 1-, 2- and 3-back conditions of the N-back. CONCLUSIONS:
      Following the complete resolution of symptoms, a history of two or more
      concussions is not associated with changes in regional brain activation during
      the performance of working memory task. Compensatory brain activation may only
      persist during the typically brief time athletes experience symptoms following
      concussion.

PMID- 22616765
TI  - Retrospective study of cytologic features of well-differentiated hepatocellular
      carcinoma in dogs.
AB  - BACKGROUND: Cytologic diagnosis of hepatocellular carcinoma is possible when
      hepatocytes have prominent criteria of malignancy, but is problematic when
      hepatocytes have a relatively normal morphologic appearance. OBJECTIVES: The aim
      of this study was to determine the cytologic features of histologically confirmed
      well-differentiated hepatocellular carcinomas (WD-HCC) in dogs to develop
      reasonable criteria for an accurate diagnosis when obvious criteria of malignancy
      in hepatocytes are lacking. METHODS: Slides of ultrasound-guided fine-needle
      aspirates of 15 histologically confirmed WD-HCC in dogs were evaluated
      retrospectively using a scoring system (0-3) established for 33 cytologic
      features. For comparison, 15 cytologic samples of non-nodular non-neoplastic
      liver were evaluated using the same criteria. Statistical analysis included
      multiple hypothesis testing using the Benjamini-Hochberg method or false
      discovery rate control to correct for multiple comparisons. RESULTS: The most
      significant and useful cytologic features in the diagnosis of canine WD-HCC were
      dissociation of hepatocytes, acinar or palisading arrangements of neoplastic
      cells, and the presence of naked nuclei and capillaries, together with mild
      anisocytosis, anisokaryosis, multinuclearity, and increased N:C ratios.
      CONCLUSIONS: Cytologic features of canine WD-HCC were determined. Further studies
      are warranted to compare these cytologic criteria among WD-HCC, hepatomas, and
      hyperplastic nodules and to examine co-variance of the 33 cytologic features.

PMID- 22616766
TI  - Dropout in the treatment of erectile dysfunction with PDE5: a study on predictors
      and a qualitative analysis of reasons for discontinuation.
AB  - INTRODUCTION: Phosphodiesterase type 5 inhibitors (PDE5) are currently the first
      line treatment for erectile dysfunction (ED). However, previous research shows
      that PDE5 treatments have high discontinuation rates. Understanding the reasons
      for discontinuing PDE5 will be necessary to optimize the response to treatment.
      AIM: The main goals were: (i) to analyze discontinuation rate of PDE5; (ii) to
      identify the discontinuation predictors; and (iii) to study the reasons for
      discontinuation using a qualitative methodology. MAIN OUTCOME MEASURES: The PDE5
      discontinuation rates, predictors, and reasons for discontinuation treatment.
      METHODS: A total of 327 men with clinical diagnosis for ED who had been treated
      with PDE5 were successfully interviewed by telephone, after giving their informed
      consent by snail mail. Telephone interviews, concerning their ongoing treatment,
      were carried out using a standardized questionnaire form with quantitative and
      qualitative items. Participation rate was 71.8%. RESULTS: Of the total sample,
      160 men (48.9%) had discontinued PDE5 treatment. The discontinuation rate was
      higher among men with diabetes (73%) and in iatrogenic group (65%), and lower in
      venogenic etiology (38.7%). We differentiated three groups of men who
      discontinued treatment (i) during the first 3 months (55.1%); (ii) between 4 and
      12 months (26.9%); and (iii) after a period of 12 months (18%). Qualitative
      analyses revealed diverse reasons for discontinuation: non-effectiveness of PDE5
      (36.8%), psychological factors (e.g., anxiety, negative emotions, fears,
      concerns, dysfunctional beliefs) (17.5%), erection recovery (14.4%), and concerns
      about the cardiovascular safety of PDE5 (8.7%) were the most common. Older men
      and men whose partners were involved in the treatment, were less likely to
      discontinue treatment. CONCLUSION: Half the subjects discontinued medication.
      Mostly, there was a combination of factors that led to discontinuation: non
      effectiveness and psychosocial factors appear to be the main reasons. Addressing
      those factors will allow following up with appropriate focus on relevant topics
      in order to improve compliance.

PMID- 22616767
TI  - One-pot, three-component synthesis of 7-azaindole derivatives from N-substituted
      2-amino-4-cyanopyrroles, various aldehydes, and active methylene compounds.
AB  - An efficient and practical route to 7-azaindole framework has been developed by
      one-pot, three-component cyclocondensation of N-substituted 2-amino-4
      cyanopyrroles, various aldehydes, and active methylene compounds in ethanol or
      acetic acid at reflux. Reactions involving tetronic acid, indane-1,3-dione,
      dimedone, and 5-phenylcyclohexane-1,3-dione gave carbocyclic fused 7-azaindoles,
      whereas Meldrum's acid, benzoylacetonitrile, and malononitrile resulted in the
      highly substituted 7-azaindole derivatives, making this strategy very useful in
      diversity-oriented synthesis (DOS). 

PMID- 22616768
TI  - C-H functionalization reactivity of a nickel-imide.
AB  - We report bifunctional reactivity of the beta-diketiminato Ni(III)-imide
      [Me(3)NN]Ni?NAd (1), which undergoes H-atom abstraction (HAA) reactions with
      benzylic substrates R-H (indane, ethylbenzene, toluene). Nickel-imide 1 competes
      with the nickel-amide HAA product [Me(3)NN]Ni-NHAd (2) for the resulting
      hydrocarbyl radical R(*) to give the nickel-amide [Me(3)NN]Ni-N(CHMePh)Ad (3) (R
      H = ethylbenzene) or aminoalkyl tautomer [Me(3)NN]Ni(eta(2)-CH(Ph)NHAd) (4) (R-H
      = toluene). A significant amount of functionalized amine R-NHAd is observed in
      the reaction of 1 with indane along with the dinickel imide {[Me(3)NN]Ni}(2)(MU
      NAd) (5). Kinetic and DFT analyses point to rate-limiting HAA from R-H by 1 to
      give R(*), which may add to either imide 1 or amide 2, each featuring significant
      N-based radical character. Thus, these studies illustrate a fundamental
      competition possible in C-H amination systems that proceed via a HAA/radical
      rebound mechanism.

PMID- 22616769
TI  - Seasonal variations in acute toxoplasmosis in pregnant women in the Rhone-Alpes
      region (France).
AB  - To search for seasonal variations we analysed data on 1998 acute toxoplasmic
      infections diagnosed between 1988 and 2009 in pregnant women. Two distinctive
      transmission profiles were observed: one in rural areas, which was strongly
      influenced by seasons with significantly fewer infections in the first half of
      the year but maximal risks at the end of summer and end of autumn, and a stable
      urban distribution with only moderate peaks. Further studies on individual risks
      and environmental and climatic factors are needed to understand what prevention
      message should be given to susceptible pregnant women.

PMID- 22616770
TI  - Prospective parallel randomized trial of the MultiCyteTM ThinPrep((r)) imaging
      system: the Scottish experience.
AB  - BACKGROUND: Computer-assisted screening of cervical liquid-based cytology (LBC)
      preparations using the ThinPrep(r) Imaging System (TIS) has shown improved
      qualitative and quantitative gains. The use of MulticyteTM has not been described
      in a well-established national screening programme with a low incidence of high
      grade dyskaryosis. OBJECTIVES: To assess the impact of computer-assisted
      screening within the Scottish Cervical Screening Programme (SCSP). METHODS: Two
      groups of three laboratories, each sharing a ThinPrep(r) Imager, screened 79 366
      slides randomized to test and 90 551 to control arms by laboratory accession.
      Screeners were not blinded. Standard laboratory reporting profiles of the SCSP,
      sensitivity, specificity and false-negative rates of all grades of LBC
      abnormalities with respect to final cytology reports, predictive value for
      cervical intraepithelial neoplasia grade 2 or worse (CIN2+) on histology; and
      screening rates were compared for both arms. RESULTS: Inadequate and negative
      reporting rates were significantly lower and low-grade reporting rates
      significantly higher in the imager arm. Imager-assisted screening showed
      significantly better specificity than manual screening with respect to the final
      cytology result. There was no evidence of a significant difference in the
      detection of CIN2+ or CIN3 +. Positive, abnormal and total predictive values
      (high-grade, low-grade and all abnormal cytology found to be CIN2+, respectively)
      were similar in both arms. Productivity was significantly higher in the imager
      arm. CONCLUSION:   Computer-assisted screening in a well established screening
      programme showed significantly improved productivity without loss of quality.
      These findings should inform future policy for cervical screening programmes.

PMID- 22616775
TI  - Palladium-catalyzed approach for the general synthesis of (E)-2-arylmethylidene-N
      tosylindolines and (E)-2-arylmethylidene-N-tosyl/nosyltetrahydroquinolines:
      access to 2-substituted indoles and quinolines.
AB  - A facile and efficient method for the synthesis of (E)-2-arylmethylidene-N
      tosylindolines and (E)-2-arylmethylidene-N-tosyl/nosyltetrahydroquinoline
      variants has been developed through palladium-catalyzed cyclocondensation of aryl
      iodides with readily available 1-(2-tosylaminophenyl)prop-2-yn-1-ols and their
      higher homologues, respectively. The proposed reaction mechanism invokes the
      operation of trans-aminopalladation during cyclization (5/6-exo-dig), which
      ensures exclusive (E)-stereochemistry in the products. The method is fast,
      operationally simple, totally regio- and stereoselective, and versatile enough to
      access a variety of 2-substituted indoles and quinolines. The reactions proceeded
      efficiently with a wide variety of substrates and afforded the corresponding
      products in moderate to excellent yields.

PMID- 22616776
TI  - Effects of autoclaving and high pressure on allergenicity of hazelnut proteins.
AB  - BACKGROUND: Hazelnut is reported as a causative agent of allergic reactions.
      However it is also an edible nut with health benefits. The allergenic
      characteristics of hazelnut-samples after autoclaving (AC) and high-pressure
      (HHP) processing have been studied and are also presented here. Previous studies
      demonstrated that AC treatments were responsible for structural transformation of
      protein structure motifs. Thus, structural analyses of allergen proteins from
      hazelnut were carried out to observe what is occurring in relation to the
      specific-IgE recognition of the related allergenic proteins. The aims of this
      work are to evaluate the effect of AC and HHP processing on hazelnut in vitro
      allergenicity using human-sera and to analyse the complexity of hazelnut allergen
      protein structures. METHODS: Hazelnut-samples were subjected to AC and HHP
      processing. The specific IgE- reactivity was studied in 15 allergic clinic
      patients via western blotting analyses. A series of homology-based-bioinformatics
      3D-models (Cora 1, Cora 8, Cora 9 and Cora 11) were generated for the antigens
      included in the study to analyse the co mplexity of their protein structure. This
      study is supported by the Declaration of Helsinki and subsequent ethical
      guidelines. RESULTS: A severe reduction in vitro in allergenicity to hazelnut
      after AC processing was observed in the allergic clinic-patients studied. The
      specific-IgE binding of some of the described immunoreactive hazelnut protein
      bands: Cora 1 ~18KDa, Cora 8 ~9KDa, Cora 9 ~35-40KDa and Cora 11 ~47-48 KDa
      decreases. Furthermore a relevant glycosylation was assigned and visualized via
      structural analysis of proteins (3D-modelling) for the first time in the protein
      allergen Cora 11 showing a new role which could open a new door for allergenicity
      unravellings. CONCLUSION: Hazelnut allergenicity-studies in vivo via Prick-Prick
      and other means using AC processing are crucial to verify the data we observed
      via in vitro analyses. Glycosylation studies provided us with clues to elucidate,
      in the near future, mechanisms of the structures that contribute to hazelnut
      allergenicity, which thus, in turn, help alleviate food allergens.

PMID- 22616777
TI  - Whole-mount confocal imaging of nuclei in giant feeding cells induced by root
      knot nematodes in Arabidopsis.
AB  - * Excellent visualization of nuclei was obtained here using a whole-mount
      procedure adapted to provide high-resolution images of large, irregularly shaped
      nuclei. The procedure is based on tissue clearing, and fluorescent staining of
      nuclear DNA with the dye propidium iodide. * The method developed for standard
      confocal imaging was applied to large multicellular root swellings, named galls,
      induced in plant hosts by the root-knot nematode Meloidogyne incognita. * Here,
      we performed a functional analysis, and examined the nuclear structure in giant
      feeding cells overexpressing the cell cycle inhibitor Kip-related protein 4
      (KRP4). Ectopic KRP4 expression in galls led to aberrant nuclear structure,
      disturbing giant cell expansion and nematode reproduction. In vivo live-cell
      imaging of GFP-KRP4 demonstrated that this protein co-localizes to chromosomes
      from prophase to late anaphase during cell cycle progression. * The data
      presented here suggest the involvement of KRP4 during mitotic progression in
      plant cells. The detailed results obtained using confocal analysis also
      demonstrate the potential utility of a rapid, easy-to-use clearing method for the
      analysis of the nuclei of certain Arabidopsis mutants and other complex plant
      nuclei.

PMID- 22616778
TI  - Synthesis of 1,1-diarylethylenes via efficient iron/copper co-catalyzed coupling
      of 1-arylvinyl halides with Grignard reagents.
AB  - An efficient access to 1,1-diarylethylenes of biological interest by coupling
      functionalized aryl Grignard reagents and 1-arylvinyl halides in the presence of
      FeCl(3)/CuTC is described. This bimetallic system proved to be superior to the
      use of Fe or Cu catalyst alone. The synthetic utility of this protocol is
      illustrated in the field of steroid chemistry.

PMID- 22616779
TI  - A method to monitor upper limb movement direction encoding in the corticomotor
      pathway.
AB  - Abnormal shoulder and elbow muscle coactivation patterns, or muscle synergies,
      are commonly present following stroke and may arise through dysfunctional
      descending neural control from the cortex. The authors evaluated a novel
      technique for examining corticomotor movement encoding of the upper limb in three
      dimensions. A 6-degree-of-freedom loadcell recorded arm twitch responses in
      healthy adults following stimulation over the cortex or over Erb's point in the
      periphery. Stimuli were delivered while the arm generated a 5 N preload in each
      of the 6 axial directions. The initial force twitch response to stimulation was
      used to construct twitch direction vectors for each preload direction. General
      linear mixed model analyses were used to determine the influence of stimulation
      location, preload direction, posture, and stimulation intensity on twitch
      direction. Cortical stimulation gave rise to arm twitch responses that were
      predictably modified by preload direction. Peripheral stimulation elicited
      stereotypical twitches that were not influenced by preload. Our stimulation,
      recording, and analysis techniques were able to capture movement encoding of the
      upper limb in three dimensions. Such techniques could be utilized in the stroke
      population to determine and monitor the presence of upper limb synergies during
      muscle activation.

PMID- 22616780
TI  - Use of a combined slit-lamp SD-OCT to obtain anterior and posterior segment
      images in selected animal species.
AB  - OBJECTIVE: To obtain images of anterior and posterior segments of the eye using a
      slit-lamp (SL)/spectral domain (SD) optical coherence tomography (OCT) integrated
      system designed for the human eye, in the cat, dog, minipig and monkey. ANIMALS
      STUDIED: One healthy adult monkey, one healthy adult minipig, one healthy adult
      dog, one healthy adult cat, and three cats and four dogs affected by corneal or
      retinal diseases. PROCEDURE: A SL SCAN-1 SD-OCT, which is a slit-lamp SL-D7 that
      contains an integrated OCT module and a fundus viewer, was used to generate OCT
      images (512-2048), while simultaneously taking 'en-face' slit-lamp images (efSL).
      OCT images were obtained under sedation or anesthesia. These images were compared
      to histological retinal sections obtained from a monkey, a minipig, a dog, and a
      cat. RESULTS: 'en-face' slit-lamp images and OCT images of the ocular tissues
      were obtained allowing for the identification of different corneal and retinal
      layers in all animal species. Measurements of the total retinal thickness (TRT)
      from the inner limiting membrane to the retinal pigment epithelium were performed
      in various regions throughout the retina. Reduction in TRT was consistent with
      clinical features of retinal degeneration identified in dogs and cats.
      CONCLUSION: This noninvasive procedure is useful for both experimental and
      clinical assessments of ocular tissue damage. Images of anterior and posterior
      segments are readily obtained under routine clinical conditions. Future studies
      are warranted to establish normal OCT data in our patients with this new
      instrument.

PMID- 22616781
TI  - An investigation into the use and limitations of different spatial integration
      schemes and finite element software in head impact analyses.
AB  - To understand the mechanopathogenesis of brain lesions, finite element (FE) head
      models are used. There is a broad range of material properties, contact
      interfaces and integration schemes used for the different parts in current FE
      head models. The effect of material behaviour and contact definitions on a head
      impact analysis is reported in the literature, whereas the effect of FE
      integration schemes is a rather unexplored domain. This paper starts with the
      development of a simplified head model to which small adaptations are made in the
      integration scheme to obtain multiple analyses that are compared using an
      accident reconstruction. The performed study highlighted potential hazards of
      different integration schemes and the significant effect they have on the
      simulated mechanical responses of the head. Based on a comparison between FE
      softwares using an impact test and patch test, it was seen that also the software
      could have an effect on the FE analysis results.

PMID- 22616782
TI  - Editorial comment to nomograms to predict the pathological stage of clinically
      localized prostate cancer in Korean men: comparison with western predictive tools
      using decision curve analysis.

PMID- 22616783
TI  - Interleukin-13 receptor alpha2: glioma's unlucky receptor?

PMID- 22616784
TI  - Surface properties of ionic liquid adsorbate layer are influenced by the dipole
      of the underneath substrate.
AB  - Ionic liquids (ILs) form nonfluidic layers at the solid-liquid interface. The
      properties of the IL interfacial layer play important roles in  IL-based
      applications. Since the liquid-phase IL directly contacts and interacts with the
      IL interfacial layer rather than the underneath substrate, the surface properties
      of the interfacial layer could influence how the IL  behaves on a solid surface.
      We used scanning probe microscopy (SPM) and force spectroscopy to investigate how
      chemical patterns with different dipoles reacted with ionic liquids. We find that
      even without direct contact on chemical patterns, the IL can form an adsorbate
      layer on chemical patterns via vapor-phase condensation. The dipole of the
      chemical pattern can direct the adsorption and assembly of the IL adsorbate. The
      surface properties of the IL adsorbate layer depend on the dipole of the
      underneath chemical patterns. Our results indicate that the interfacial IL layer
      may exist before the IL contacts a solid surface. The charge and dipole of the
      substrate can influence the structures and properties of the IL interfacial
      layer. Characterization and measurements of the IL interfacial properties must be
      conducted under the pretext that the charge/dipole of the substrate is known.

PMID- 22616786
TI  - Influence of substrate orientation on exciton fine structure splitting of
      InAs/InP nanowire quantum dots.
AB  - : In this paper, we use an atomistic approach to investigate strain
      distributions, single particle and many body electronic properties of InAs/InP
      nanowire quantum dots with substrate orientation varying from [111] to high-index
      [119], and compared with [001] case. We show that single particle gap for high
      index [11k] substrates is increased with respect to [111] and [001] cases, and
      oscillates with the substrate index due to faceting effects. Surprisingly, the
      overall shell-like structure of single particle states is preserved even for
      highly facetted, high-index substrates. On the contrary, we demonstrate that
      besides two limiting high-symmetry cases, [001] and [111], the bright exciton
      splitting varies strongly with substrate orientation. For [112]-oriented
      substrate, the fine structure splitting reaches maximum due to crystal lattice
      anisotropy despite fully cylindrical isotropic shape of nanowire quantum dot.

PMID- 22616785
TI  - Influence of the intentional voice quality on the impression of female speaker.
AB  - This study examines the relationship of voice quality and speech-based
      personality assessment of Finnish-speaking female speakers. Five Finnish-speaking
      female subjects recorded a text passage with eight different vocal qualities.
      Samples that passed the preselection test for the voice qualities were played to
      50 Finnish-speaking listeners, who reported speaker impressions on a scale of 18
      opposite trait pairs. Voices produced with forward placement received assessments
      of femininity and friendliness. Readers speaking with backward placement were
      considered less feminine, while breathy voice evoked assessments of emotionality
      and implausibility. Tense phonation as well as creakiness, nasality, and
      denasality gave rise to numerous negative notions. The results suggest that voice
      stereotypes have both internationality and cultural dependency.

PMID- 22616787
TI  - Addition of halloysite nanotubes prevents cracking in drying latex films.
AB  - Investigating the process of film drying from aqueous dispersions containing a
      polymer latex as well as halloysite nanotubes (HNTs), we found that composite
      films could be formed without cracking under conditions where films of the pure
      polymer would always crack. Scanning electron micrographs showed that the HNTs
      were well dispersed and, further, that the distribution of fiber orientations was
      close to isotropic. The pendulum hardness of films formed from acrylate
      dispersions strongly increased upon addition of the inorganic phase. The pencil
      hardness, on the other hand, was poor, which presumably goes back to insufficient
      coupling between the organic and the inorganic phase. All films were white in
      appearance. For fiber concentrations higher than 10 vol %, the final films were
      porous.

PMID- 22616789
TI  - The minimal relationship between simulation fidelity and transfer of learning.
AB  - CONTEXT: High-fidelity simulators have enjoyed increasing popularity despite
      costs that may approach six figures. This is justified on the basis that
      simulators have been shown to result in large learning gains that may transfer to
      actual patient care situations. However, most commonly, learning from a simulator
      is compared with learning in a 'no-intervention' control group. This fails to
      clarify the relationship between simulator fidelity and learning, and whether
      comparable gains might be achieved at substantially lower cost. OBJECTIVES: This
      analysis was conducted to review studies that compare learning from high-fidelity
      simulation (HFS) with learning from low-fidelity simulation (LFS) based on
      measures of clinical performance. METHODS: Using a variety of search strategies,
      a total of 24 studies contrasting HFS and LFS and including some measure of
      performance were located. These studies referred to learning in three areas:
      auscultation skills; surgical techniques, and complex management skills such as
      cardiac resuscitation. RESULTS: Both HFS and LFS learning resulted in consistent
      improvements in performance in comparisons with no-intervention control groups.
      However, nearly all the studies showed no significant advantage of HFS over LFS,
      with average differences ranging from 1% to 2%. DISCUSSION: The factors
      influencing learning, and the reasons for this surprising finding, are discussed.

PMID- 22616788
TI  - Mass spectrometry "sensor" for in vivo acetylcholine monitoring.
AB  - Developing sensors for in vivo chemical monitoring is a daunting challenge. An
      alternative approach is to couple sampling methods with online analytical
      techniques; however, such approaches are generally hampered by lower temporal
      resolution and slow analysis. In this work, microdialysis sampling was coupled
      with segmented flow electrospray ionization mass spectrometry (ESI-MS) to perform
      in vivo chemical monitoring. The use of segmented flow to prevent Taylor
      dispersion of collected zones and rapid analysis with direct ESI-MS allowed 5 s
      temporal resolution to be achieved. The MS "sensor" was applied to monitor
      acetylcholine in the brain of live rats. The detection limit of 5 nM was
      sufficient to monitor basal acetylcholine as well as dynamic changes elicited by
      microinjection of neostigmine, an inhibitor of acetylcholinesterase, that evoked
      rapid increases in acetycholine and tetrodotoxin, a blocker of Na(+) channels,
      that lowered the acetylcholine concentration. The versatility of the sensor was
      demonstrated by simultaneously monitoring metabolites and infused drugs.

PMID- 22616790
TI  - Effect of chiral diene ligands in rhodium-catalyzed asymmetric addition of
      arylboronic acids to alpha,beta-unsaturated sulfonyl compounds.
AB  - Asymmetric addition of arylboronic acids to alpha,beta-unsaturated sulfonyl
      compounds proceeded in the presence of a rhodium catalyst coordinated with a
      chiral diene ligand to give high yields of the addition products with high
      enantioselectivity (96->99.5% ee). The diene ligand was proved to be essential
      for the formation of the addition products, while the use of a bisphosphine
      ligand mainly gave the cine-substitution product.

PMID- 22616791
TI  - Splitting random forest (SRF) for determining compact sets of genes that
      distinguish between cancer subtypes.
AB  - BACKGROUND: The identification of very small subsets of predictive variables is
      an important topic that has not often been considered in the literature. In order
      to discover highly predictive yet compact gene set classifiers from whole genome
      expression data, a non-parametric, iterative algorithm, Splitting Random Forest
      (SRF), was developed to robustly identify genes that distinguish between
      molecular subtypes. The goal is to improve the prediction accuracy while
      considering sparsity. RESULTS: The optimal SRF 50 run (SRF50) gene classifiers
      for glioblastoma (GB), breast (BC) and ovarian cancer (OC) subtypes had overall
      prediction rates comparable to those from published datasets upon validation
      (80.1%-91.7%). The SRF50 sets outperformed other methods by identifying compact
      gene sets needed for distinguishing between tested cancer subtypes (10-200 fold
      fewer genes than ANOVA or published gene sets). The SRF50 sets achieved superior
      and robust overall and subtype prediction accuracies when compared with single
      random forest (RF) and the Top 50 ANOVA results (80.1% vs 77.8% for GB; 84.0% vs
      74.1% for BC; 89.8% vs 88.9% for OC in SRF50 vs single RF comparison; 80.1% vs
      77.2% for GB; 84.0% vs 82.7% for BC; 89.8% vs 87.0% for OC in SRF50 vs Top 50
      ANOVA comparison). There was significant overlap between SRF50 and published gene
      sets, showing that SRF identifies the relevant sub-sets of important gene lists.
      Through Ingenuity Pathway Analysis (IPA), the overlap in "hub" genes between the
      SRF50 and published genes sets were RB1, piK3R1, PDGFBB and ERK1/2 for GB; ESR1,
      MYC, NFkB and ERK1/2 for BC; and Akt, FN1, NFkB, PDGFBB and ERK1/2 for OC.
      CONCLUSIONS: The SRF approach is an effective driver of biomarker discovery
      research that reduces the number of genes needed for robust classification,
      dissects complex, high dimensional "omic" data and provides novel insights into
      the cellular mechanisms that define cancer subtypes.

PMID- 22616793
TI  - Enantiopure synthesis of side chain-modified alpha-amino acids and 5-cis
      alkylprolines.
AB  - A short, concise synthesis of enantiopure, side chain-modified alpha-amino acids
      such as 4-oxo-L-norvaline, 6-oxo-L-homonorleucine, and 5-cis-alkyl prolines is
      described. Knoevenagel condensation of l-aminocarboxylate-derived beta-ketoesters
      with aldehydes followed by reductive decarboxylation results in unnatural alpha
      amino acids in good yield. A fluorescent amino acid is synthesized using a
      similar protocol. These studies show that aminocarboxylate-derived beta
      ketoesters are very useful intermediates and the method employed is both general
      and practical for the preparation of gamma(delta)-oxo alpha-amino acids and
      alkylprolines.

PMID- 22616792
TI  - Cumulative advantages and the emergence of social and ethnic inequality: Matthew
      effects in reading and mathematics development within elementary schools?
AB  - This article examines the development of social and ethnic disparities in
      academic achievement in elementary schooling. It investigated whether reading and
      mathematics development in 136 mixed-ability classes shows path-dependent
      processes of cumulative advantage (Matthew effects) from Grades 4 to 6 (Grade 4
      mean age = 10.62, SD = 0.57) resulting in growing inequality. Status-dependent
      processes of cumulative advantage, their interaction with path-dependent
      processes, and consequences for the degree of social and ethnic inequality are
      examined. Two complementary methods for analyzing multilevel data are used:
      growth curve and quasi-simplex models. No evidence for a Matthew effect was found
      in either domain. A compensation effect emerged for reading, to the benefit of
      ethnic minorities. A fan-spread effect was found for mathematics, partly
      attributable to status-dependent processes of cumulative advantage.

PMID- 22616794
TI  - Proteinuria after kidney transplantation.
AB  - The prevalence of proteinuria at 1 year after renal transplantation ranges
      between 11% and 45% and is even higher in patients treated with inhibitors of the
      mammalian target of rapamycin (mTOR). Two main mechanisms can lead to
      proteinuria: an inadequate reabsorption of small proteins from proximal tubular
      cells damaged by ischemia-reperfusion injury, rejection, or toxic agents (tubular
      proteinuria) or an increased passage of albumin and/or protein with higher
      molecular weight (MW) because of a disruption of glomerular barrier caused by
      recurrent or de novo glomerulonephritis, transplant glomerulopathy, chronic
      rejection, or CNI toxicity (glomerular proteinuria). Proteinuric patients have
      worse patient and graft survival rates in comparison to non proteinuric patients.
      The amount of proteinuria is a reliable predictor of the allograft outcome.
      However, even microalbuminuria may be associated with a poor outcome. Treatment
      of proteinuria mainly rests on the management of the etiologic cause. Inhibitors
      of renin-angiotensin system (RAS) are useful in reversing microalbuminuria and
      can reduce proteinuria, but their efficacy in interfering with patient or graft
      survival is not demonstrated.

PMID- 22616795
TI  - The acceptance of prolonged CPR donors in pediatric heart transplant recipients:
      are we ready to push the envelope?

PMID- 22616797
TI  - Brainstem injury by penetrating head trauma with a knife.
AB  - The authors describe a rare case about a traumatic lesion of brain and brain stem
      with a knife. In this case the patient had good clinical condition, diagnosed
      with TBI by infectious complications. We have highlighted the unusual diagnosis,
      proximity of vascular structures, the technique used in the treatment and the
      good outcome of the injury.

PMID- 22616796
TI  - Aetheramides A and B, potent HIV-inhibitory depsipeptides from a myxobacterium of
      the new genus "Aetherobacter".
AB  - Aetheramides are structurally distinctive cyclic peptides isolated from a novel
      myxobacterial genus proposed to be termed "Aetherobacter". The structures were
      solved by a combination of NMR analyses, quantum mechanical calculations, and
      chemical derivatizations. Aetheramides which contain a unique polyketide moiety
      and two amino acid residues potently inhibited HIV-1 infection with IC(50) values
      of ~0.015 MUM. Furthermore aetheramides showed cytostatic activity against human
      colon carcinoma (HCT-116) cells with IC(50) values of 0.11 MUM.

PMID- 22616798
TI  - Primary dural follicular lymphoma masquerading as meningioma: a case report.
AB  - Patient presented with a dural-based mass lesion and was diagnosed as having
      meningioma on imaging. Post-resection histological examination revealed a low
      grade follicular lymphoma. The patient received cranial radiotherapy and is
      recurrence-free at 6-month follow-up. Primary dural follicular lymphoma is an
      exceedingly rare entity with only as few as six reported cases. Herein, the
      clinico-radio-pathological appearances and treatment protocol of this entity are
      discussed.

PMID- 22616799
TI  - The relationships between preoperative sexual desire and quality of life
      following radical prostatectomy: a 5-year follow-up study.
AB  - INTRODUCTION: There were few studies about the relationship between sexual desire
      (SD) and radical prostatectomy (RP). AIMS: We assessed the relationships between
      RP and quality of life (QOL) according to the preoperative SD. MAIN OUTCOME
      MEASURE: General QOL was measured with Short Form 36. Sexual function and bother
      were measured with the University of California, Los Angeles Prostate Cancer
      Index (PCI). Changes of postoperative SD were also evaluated using PCI. METHODS:
      We analyzed data from 285 men who underwent RP and were prospectively enrolled
      into a longitudinal cohort study. Patients were divided into two groups according
      to whether they had SD at baseline, which is addressed in the PCI questionnaire:
      a low SD (LSD) group and a high SD (HSD) group. The assessments were completed
      before treatment and 3, 6, 12, 24, and 60 months after RP. RESULTS: Of the 244
      men, 52% had high or a fair level of SD before RP, whereas 48% reported that the
      level of their SD was low. The HSD group reported better sexual function and
      sexual bother scores than the LSD group at baseline (both P < 0.001). Fifty-one
      percent of the HSD group reported that SD at 3 months was poor or very poor,
      which did not return to the preoperative level at all postoperative time points.
      Nearly 20% of the LSD group regained higher SD after RP than the baseline level.
      The HSD group showed worse sexual bother scores than the baseline throughout the
      postoperative follow-up (P < 0.001). However, the LSD group demonstrated
      equivalent sexual bother scores after RP compared with the baseline. CONCLUSIONS:
      RP adversely affected SD as well as sexual function and sexual bother. The
      patients who had HSD experienced greater distress concerning their sexual
      dysfunction postoperatively than those with LSD.

PMID- 22616801
TI  - Copper-decorated carbon nanotubes-based composite electrodes for nonenzymatic
      detection of glucose.
AB  - The aim of this study was to prepare three types of multiwall carbon nanotubes
      (CNT)-based composite electrodes and to modify their surface by copper
      electrodeposition for nonenzymatic oxidation and determination of glucose from
      aqueous solution. Copper-decorated multiwall carbon nanotubes composite electrode
      (Cu/CNT-epoxy) exhibited the highest sensitivity to glucose determination.

PMID- 22616802
TI  - What is your diagnosis? Duodenal brush preparation from a dog.

PMID- 22616803
TI  - Structural and mechanical integrity of tendon-to-tendon attachments used in upper
      limb tendon transfer surgery.
AB  - Improved tendon-to-tendon suturing techniques allow for consistent and immediate
      activation of transferred muscle after surgery. A pre-requisite for early
      training after tendon transfer surgery is sufficient mechanical integrity of the
      tendon-to-tendon attachment. This in vitro study compared the mechanisms and
      magnitudes of load-to-failure response of two different repair techniques (side
      to-side running, n = 7) and weave sutures (n = 8) in sheep front foot tendons.
      Tensile tests were performed by placing pre-conditioned tendons in a testing
      machine and stretching at a constant speed to failure. The length of the tendons
      overlap was the same (50 mm) for both repair techniques. The results of the load
      to failure tests showed that the side-to-side repairs were significantly stronger
      than the weave repairs. The failure mechanisms were also different. While the
      side-to-side attachment failed by longitudinal separation of tendon material of
      the donor tendon but with the fibres locked to the running sutures attached to
      the recipient tendon, the weave repairs failed by knot slipping or by suture
      pullout from the tendon substance. It is concluded that use of the side-to-side
      repair technique can provide early active training of new motors that not only
      prevent the formation of adhesions but also facilitate the voluntary recruitment
      of motors powering new functions before immobilisation-related swelling and
      stiffness restrain muscle contractions.

PMID- 22616800
TI  - Visual scanning patterns and executive function in relation to facial emotion
      recognition in aging.
AB  - OBJECTIVE: The ability to perceive facial emotion varies with age. Relative to
      younger adults (YA), older adults (OA) are less accurate at identifying fear,
      anger, and sadness, and more accurate at identifying disgust. Because different
      emotions are conveyed by different parts of the face, changes in visual scanning
      patterns may account for age-related variability. We investigated the relation
      between scanning patterns and recognition of facial emotions. Additionally, as
      frontal-lobe changes with age may affect scanning patterns and emotion
      recognition, we examined correlations between scanning parameters and performance
      on executive function tests. METHODS: We recorded eye movements from 16 OA (mean
      age 68.9) and 16 YA (mean age 19.2) while they categorized facial expressions and
      non-face control images (landscapes), and administered standard tests of
      executive function. RESULTS: OA were less accurate than YA at identifying fear (p
      < .05, r = .44) and more accurate at identifying disgust (p < .05, r = .39). OA
      fixated less than YA on the top half of the face for disgust, fearful, happy,
      neutral, and sad faces (p values < .05, r values >= .38), whereas there was no
      group difference for landscapes. For OA, executive function was correlated with
      recognition of sad expressions and with scanning patterns for fearful, sad, and
      surprised expressions. CONCLUSION: We report significant age-related differences
      in visual scanning that are specific to faces. The observed relation between
      scanning patterns and executive function supports the hypothesis that frontal
      lobe changes with age may underlie some changes in emotion recognition.

PMID- 22616804
TI  - Parental estimation of early psychological development in children operated on
      for single suture synostosis.
AB  - Impaired psychological development in children with single suture
      craniosynostosis is often described in the literature. The authors' own
      experience was that these children appeared to have normal psychological
      development during their first years of life. The aim of the present study was,
      therefore, to evaluate if parental estimation would reveal any shortcomings in
      psychological development. All consecutive patients operated on for non-syndromal
      single suture synostosis between October 2002 and June 2006 were included (n =
      66). A questionnaire was filled out by the parents when the child was 3 years
      old. The questions concerned development of speech, motor control, personal
      abilities, and emotional development. The results were compared with randomly
      selected controls of the same age (n = 180) whose parents answered the same
      questionnaire. The results showed that children operated on for single suture
      synostosis did not show any signs of lasting disadvantages due to craniofacial
      surgery. The children did not in any respect suffer from a hampered psychological
      development up to 3 years of age. In summary the psychological development of
      patients operated on for single suture synostosis seems to be normal up to 3
      years of age as far as parental estimation can reveal.

PMID- 22616805
TI  - Interaction of diabetes and ACE2 in the pathogenesis of cardiovascular disease in
      experimental diabetes.
AB  - Local and systemic AngII (angiotensin II) levels are regulated by ACE2
      (angiotensin-converting enzyme 2), which is reduced in diabetic tissues. In the
      present study, we examine the effect of ACE2 deficiency on the early cardiac and
      vascular changes associated with experimental diabetes. Streptozotocin diabetes
      was induced in male C57BL6 mice and Ace2-KO (knockout) mice, and markers of RAS
      (renin-angiotensin system) activity, cardiac function and injury were assessed
      after 10 weeks. In a second protocol, diabetes was induced in male ApoE
      (apolipoprotein E)-KO mice and ApoE/Ace2-double-KO mice, and plaque accumulation
      and markers of atherogenesis assessed after 20 weeks. The induction of diabetes
      in wild-type mice led to reduced ACE2 expression and activity in the heart,
      elevated circulating AngII levels and reduced cardiac Ang-(1-7) [angiotensin-(1
      7)] levels. This was associated structurally with thinning of the LV (left
      ventricular) wall and mild ventricular dilatation, and histologically with
      increased cardiomyocyte apoptosis on TUNEL (terminal deoxynucleotidyl transferase
      mediated dUTP nick-end labelling) staining and compensatory hypertrophy denoted
      by an increased cardiomyocyte cross-sectional area. By contrast Ace2-KO mice
      failed to increase circulating AngII concentration, experienced a paradoxical
      fall in cardiac AngII levels and no change in Ang-(1-7) following the onset of
      diabetes. At the same time the major phenotypic differences between Ace2
      deficient and Ace2-replete mice with respect to BP (blood pressure) and cardiac
      hypertrophy were eliminated following the induction of diabetes. Consistent with
      findings in the heart, the accelerated atherosclerosis that was observed in
      diabetic ApoE-KO mice was not seen in diabetic ApoE/Ace2-KO mice, which
      experienced no further increase in plaque accumulation or expression in key
      adhesion molecules beyond that seen in ApoE/Ace2-KO mice. These results point to
      the potential role of ACE2 deficiency in regulating the tissue and circulating
      levels of AngII and their sequelae in the context of diabetes, as well as the
      preservation or augmentation of ACE2 expression or activity as a potential
      therapeutic target for the prevention of CVD (cardiovascular disease) in
      diabetes.

PMID- 22616806
TI  - H2O2-mediated oxidation of zero-valent silver and resultant interactions among
      silver nanoparticles, silver ions, and reactive oxygen species.
AB  - The H(2)O(2)-mediated oxidation of silver nanoparticles (AgNPs) over a range of
      pH (3.0-14.0) is investigated here, and an electron charging-discharging model
      capable of describing the experimental results obtained is developed. AgNPs
      initially react with H(2)O(2) to form Ag(+) and superoxide, with these products
      subsequently reacting to reform AgNPs (in-situ-formed AgNPs) via an electron
      charging-discharging mechanism. Our experimental results show that the AgNP
      reactivity toward H(2)O(2) varies significantly with pH, with the variation at
      high pH (>10) due particularly to the differences in the reactivity of H(2)O(2)
      and its conjugate base HO(2)(-) with AgNPs whereas at lower pH (3-10) the pH
      dependence of H(2)O(2) decay is accounted for, at least in part, by the pH
      dependence of the rate of superoxide disproportionation. Our results further
      demonstrate that the in-situ-formed AgNPs resulting from the superoxide-mediated
      reduction of Ag(+) have a different size and reactivity compared to those of the
      citrate-stabilized particles initially present. The turnover frequency for AgNPs
      varies significantly with pH and is as high as 1776.0 min(-1) at pH 11.0,
      reducing to 144.2 min(-1) at pH 10.0 and 3.2 min(-1) at pH 3.0.

PMID- 22616807
TI  - HHV-6B is frequently found in the gastrointestinal tract in kidney
      transplantation patients.
AB  - In immunosuppressed patients human herpesvirus 6 (HHV-6) reactivations are
      common. The aim of the study was to determine to which extent HHV-6 can be found
      in the gastrointestinal tract in kidney transplant recipients and in patients on
      chronic dialysis. The HHV-6 and cytomegalovirus (CMV) examinations were performed
      on gastro duodenal and colon biopsy specimens obtained from 81 kidney transplant
      recipients and on 46 chronic dialysis patients. The HHV-6 and CMV were
      demonstrated by immunohistochemistry detecting both HHV-6A and HHV-6B, and CMV
      specific antigens. The HHV-6B-positive cells, were found in gastroduodenal biopsy
      specimens from 34% of the transplant recipients and 28% of the patients on
      chronic dialysis, CMV-positive cells were found in specimens from 53% of the
      transplant recipients and 28% of the patients on chronic dialysis. The HHV-6B
      positive cells were found in the colonic mucosa specimens from 36% of the
      transplant recipients and 22% of the patients on chronic dialysis, CMV-positive
      cells were found in specimens from 36% of the transplant recipients and 17% of
      the patients on chronic dialysis. The HHV-6B positive cells were found equally
      often in the gastroduodenal as in the colorectal mucosa. The HHV-6B positive
      cells as well as CMV positive cells were simultaneously found in every fifth of
      transplant recipients.

PMID- 22616808
TI  - UV-photoelectron spectroscopy of 1,2- and 1,3-azaborines: a combined experimental
      and computational electronic structure analysis.
AB  - We present a comprehensive electronic structure analysis of structurally simple
      BN heterocycles using a combined UV-photoelectron spectroscopy (UV
      PES)/computational chemistry approach. Gas-phase He I photoelectron spectra of
      1,2-dihydro-1,2-azaborine 1, N-Me-1,2-BN-toluene 2, and N-Me-1,3-BN-toluene 3
      have been recorded, assessed by density functional theory calculations, and
      compared with their corresponding carbonaceous analogues benzene and toluene. The
      first ionization energies of these BN heterocycles are in the order N-Me-1,3-BN
      toluene 3 (8.0 eV) < N-Me-1,2-BN-toluene 2 (8.45 eV) < 1,2-dihydro-1,2-azaborine
      1 (8.6 eV) < toluene (8.83 eV) < benzene (9.25 eV). The computationally
      determined molecular dipole moments are in the order 3 (4.577 D) > 2 (2.209 D) >
      1 (2.154 D) > toluene (0.349 D) > benzene (0 D) and are consistent with
      experimental observations. The lambda(max) in the UV-vis absorption spectra are
      in the order 3 (297 nm) > 2 (278 nm) > 1 (269 nm) > toluene (262 nm) > benzene
      (255 nm). We also establish that the measured anodic peak potentials and
      electrophilic aromatic substitution (EAS) reactivity of BN heterocycles 1-3 are
      consistent with the electronic structure description determined by the combined
      UV-PES/computational chemistry approach.

PMID- 22616809
TI  - Human psychometric and taste receptor responses to steviol glycosides.
AB  - Steviol glycosides, the sweet principle of Stevia Rebaudiana (Bertoni) Bertoni,
      have recently been approved as a food additive in the EU. The herbal non
      nutritive high-potency sweeteners perfectly meet the rising consumer demand for
      natural food ingredients in Europe. We have characterized the organoleptic
      properties of the most common steviol glycosides by an experimental approach
      combining human sensory studies and cell-based functional taste receptor
      expression assays. On the basis of their potency to elicit sweet and bitter taste
      sensations, we identified glycone chain length, pyranose substitution, and the
      C16 double bond as the structural features giving distinction to the gustatory
      profile of steviol glycosides. A comprehensive screening of 25 human bitter taste
      receptors revealed that two receptors, hTAS2R4 and hTAS2R14, mediate the bitter
      off-taste of steviol glycosides. For some test substances, e.g., stevioside, we
      observed a decline in sweet intensity at supra-maximum concentrations. This
      effect did not arise from allosteric modulation of the hTAS1R2/R3 sweet taste
      receptor but might be explained by intramolecular cross-modal suppression between
      the sweet and bitter taste component of steviol glycosides. These results might
      contribute to the production of preferentially sweet and least bitter tasting
      Stevia extracts by an optimization of breeding and postharvest downstream
      processing. 

PMID- 22616810
TI  - Whole-body tissue distribution of total radioactivity in rats after oral
      administration of [14C]-bilastine.
AB  - This study evaluated the tissue distribution of total radioactivity in male
      albino, male pigmented, and time-mated female albino rats after oral
      administration of a single dose of [14C]-bilastine (20 mg/kg). Although only 1
      animal was analyzed at each time point, there were apparent differences in
      bilastine distribution. Radioactivity was distributed to only a few tissues at
      low levels in male rats, whereas distribution was more extensive and at higher
      levels in female rats. This may be a simple sex-related difference. In each group
      and at each time point, concentrations of radioactivity were high in the liver
      and kidney, reflecting the role of these organs in the elimination process. In
      male albino rats, no radioactivity was measurable by 72 hours postdose. In male
      pigmented rats, only the eye and uveal tract had measurable levels of
      radioactivity at 24 hours. Measureable levels of radioactivity were retained in
      these tissues at the final sampling time point (336 hours postdose), indicating a
      degree of melanin-associated binding. In time-mated female rats, but not in
      albino or pigmented male rats, there was evidence of low-level passage of
      radioactivity across the placental barrier into fetal tissues as well as low
      level transfer of radioactivity into the brain.

PMID- 22616811
TI  - Interactions of bilastine, a new oral H1 antihistamine, with human transporter
      systems.
AB  - Membrane transporters play a significant role in facilitating transmembrane drug
      movement. For new pharmacological agents, it is important to evaluate potential
      interactions (e.g., substrate specificity and/or inhibition) with human
      transporters that may affect their pharmacokinetics, efficacy, or toxicity.
      Bilastine is a new nonsedating H1 antihistamine indicated for the treatment of
      allergic rhinoconjunctivitis and urticaria. The in vitro inhibitory effects of
      bilastine were assessed on 12 human transporters: four efflux [multidrug
      resistance protein 1 (MDR1) or P-glycoprotein, breast cancer resistance protein
      (BCRP), multidrug resistance associated protein 2 (MRP2), and bile salt export
      pump) and eight uptake transporters (sodium taurocholate cotransporting
      polypeptide, organic cation transporter (OCT)1, organic anion transporter (OAT)1,
      OAT3, OCT2, OATP2B1, OATP1B1, and OATP1B3). Only mild inhibition was found for
      MDR1-, OCT1-, and OATP2B1-mediated transport of probe substrates at the highest
      bilastine concentration assayed (300 MUM; half-maximal inhibitory concentration:
      >=300 MUM). Bilastine transport by MDR1, BCRP, OAT1, OAT3, and OCT2 was also
      investigated in vitro. Only MDR1 active transport of bilastine was relevant,
      whereas it did not appear to be a substrate of OCT2, OAT1, or OAT3, nor was it
      transported substantially by BCRP. Drug-drug interactions resulting from
      bilastine inhibition of drug transporters that would be generally regarded as
      clinically relevant are unlikely. Additionally, bilastine did not appear to be a
      substrate of human BCRP, OAT1, OAT3, or OCT2 and thus is not a potential victim
      of inhibitors of these transporters. On the other hand, based on in vitro
      evaluation, clinically relevant interactions with MDR1 inhibitors are
      anticipated.

PMID- 22616812
TI  - An overview of bilastine metabolism during preclinical investigations.
AB  - Knowledge of the biotransformation of oral H1 antihistamines is clinically
      important because it can define their pharmacokinetic profile through possible
      effects on absorption (i.e., first-pass metabolism) and elimination. Further,
      clinically significant interactions with inhibitors of cytochrome P450 (CYP) have
      previously been reported for drugs of this therapeutic group, such as terfenadine
      and astemizole, indicating the possibility of drug-drug interactions involving
      agents that share the same metabolic pathway. The aim of this article was to
      review the preclinical testing of a new antihistamine (i.e., bilastine) in terms
      of its biotransformation in various animal species, including humans, and to
      evaluate its potential for possible drug-drug interactions involving the CYP
      system. A wide array of preclinical experiments were reviewed, all of which
      demonstrated that bilastine undergoes minimal metabolism in all species tested to
      date, including humans. Further, bilastine did not interact significantly, either
      as an inhibitor or inducer, with the CYP enzyme system, suggesting a low
      propensity for involvement in drug-drug interactions. These characteristics
      demonstrate the potential for bilastine to be a good choice for allergic patients
      receiving treatment for other concomitant diseases, including those with renal or
      hepatic dysfunction.

PMID- 22616813
TI  - Preclinical toxicity profile of oral bilastine.
AB  - As part of the bilastine development program, and as mandated by regulatory
      authorities, several studies were performed with oral bilastine in different
      animal species to evaluate its toxicity profile. Toxicokinetic analyses conducted
      in tandem to evaluate systemic exposure, gender differences, and dose
      proportionality in the different animal species indicated that animals were
      systemically exposed to bilastine during treatment. Repeated-dose toxicity
      studies in beagle dogs (52 weeks) and in rats and mice (13 weeks) showed that
      bilastine at doses up to 2,000 mg/kg/day was not associated with any mortality,
      ocular effects, or nodules/masses. Likewise, no bilastine-associated neoplastic
      lesions were observed in rats and mice after 104 weeks of treatment with
      bilastine at doses up to 2,000 mg/kg/day. In general, bilastine-related clinical
      signs, body-weight changes, food consumption, clinical chemistry, haematology,
      and macro- and microscopic findings were of low order and reversible, with
      effects present only at the highest doses administered. Bilastine (up to 1,000
      mg/kg/day) was well tolerated in pregnant/lactating rats and in their offspring
      and subsequent generations. With respect to effects on embryofoetal development
      in rabbits, bilastine at 400 mg/kg/day (the highest dose evaluated) was assessed
      to be the no observed adverse effects level. Overall, bilastine demonstrated a
      favorable toxicity profile in all animal models investigated and at higher doses
      than the corresponding recommended daily human dosage.

PMID- 22616814
TI  - Experimental and theoretical analyses of azulene synthesis from tropones and
      active methylene compounds: reaction of 2-methoxytropone and malononitrile.
AB  - A representative azulene formation from an active troponoid precursor (2
      methoxytropone) and an active methylene compound (malononitrile) has been
      analyzed both experimentally and theoretically. (2)H-Tracer experiments using 2
      methoxy[3,5,7-(2)H(3)]tropone (2-d(3)) and malononitrile anion give 2-amino-1,3
      dicyano[4,6,8-(2)H(3)]azulene (1-d(3)) in quantitative yield. New and stable (2)H
      incorporated reaction intermediates have been isolated, and main intermediates
      have been detected by careful low-temperature NMR measurements. The detection has
      been guided by mechanistic considerations and B3LYP/6-31(+)G(d) calculations. The
      facile and quantitative one-pot formation of azulene 1 has been found to consist
      of a number of consecutive elementary processes: (a) The troponoid substrate, 2
      methoxytropone (2), is subject to a nucleophilic substitution by the attack of
      malononitrile anion (HC(CN)(2)(-)) to form a Meisenheimer-type complex 3, which
      is rapidly converted to 2-troponylmalononitrile anion (5). (b) The anion 5 is
      converted to an isolable intermediate, 2-imino-2H-cyclohepta[b]furan-3
      carbonitrile (6), by the first ring closure in the reaction. (c) A nucleophilic
      addition of the second HC(CN)(2)(-) toward the imine 6 at the C-8a position
      produces the second Meisenheimer-type adduct 7. (d) The second ring closure leads
      to 1-carbamoyl-1,3-dicyano-2-imino-2,3-dihydroazulene (11). A base attacks the
      imine 11, which results in generation of a conjugate base 12 of the final
      product, azulene 1.

PMID- 22616815
TI  - Biomechanical behaviour of ankle ligaments: constitutive formulation and
      numerical modelling.
AB  - This study was aimed at the definition of a constitutive formulation of ankle
      ligaments and of a procedure for the constitutive parameters evaluation, for the
      biomechanical analysis by means of numerical models. To interpret the typical
      features of ligaments mechanical response, as anisotropic configuration,
      geometric non-linearity, non-linear elasticity and time-dependent behaviour, a
      specific fibre-reinforced visco-hyperelastic model is provided. The
      identification of constitutive parameters is performed by a stochastic
      deterministic procedure that minimises the discrepancy between experimental and
      computational results. A preliminary evaluation of parameters is performed by
      analytical models in order to define reference values. Afterwards, solid models
      are developed to consider the complex histo-morphometric configuration of samples
      as a basis for the definition of numerical models. The results obtained are
      adopted for upgrading parameter values by comparison with specific mechanical
      tests. Assuming the new parameters set, the final numerical results are compared
      with the overall set of experimental data, to assess the reliability and efficacy
      of the analysis developed for the interpretation of the mechanical response of
      ankle ligaments.

PMID- 22616817
TI  - C. elegans PAT-9 is a nuclear zinc finger protein critical for the assembly of
      muscle attachments.
AB  - BACKGROUND: Caenorhabditis elegans sarcomeres have been studied extensively
      utilizing both forward and reverse genetic techniques to provide insight into
      muscle development and the mechanisms behind muscle contraction. A previous
      genetic screen investigating early muscle development produced 13 independent
      mutant genes exhibiting a Pat (paralyzed and arrested elongation at the two-fold
      length of embryonic development) muscle phenotype. This study reports the
      identification and characterization of one of those genes, pat-9. RESULTS:
      Positional cloning, reverse genetics, and plasmid rescue experiments were used to
      identify the predicted C. elegans gene T27B1.2 (recently named ztf-19) as the pat
      9 gene. Analysis of pat-9 showed it is expressed early in development and within
      body wall muscle lineages, consistent with a role in muscle development and
      producing a Pat phenotype. However, unlike most of the other known Pat gene
      family members, which encode structural components of muscle attachment sites,
      PAT-9 is an exclusively nuclear protein. Analysis of the predicted PAT-9 amino
      acid sequence identified one putative nuclear localization domain and three C2H2
      zinc finger domains. Both immunocytochemistry and PAT-9::GFP fusion expression
      confirm that PAT-9 is primarily a nuclear protein and chromatin
      immunoprecipitation (ChIP) experiments showed that PAT-9 is present on certain
      gene promoters. CONCLUSIONS: We have shown that the T27B1.2 gene is pat-9.
      Considering the Pat-9 mutant phenotype shows severely disrupted muscle attachment
      sites despite PAT-9 being a nuclear zinc finger protein and not a structural
      component of muscle attachment sites, we propose that PAT-9 likely functions in
      the regulation of gene expression for some necessary structural or regulatory
      component(s) of the muscle attachment sites.

PMID- 22616816
TI  - The changing epidemiology of Staphylococcus aureus bloodstream infection: a
      multinational population-based surveillance study.
AB  - Although the epidemiology of Staphylococcus aureus bloodstream infection (BSI)
      has been changing, international comparisons are lacking. We sought to determine
      the incidence of S. aureus BSI and assess trends over time and by region.
      Population-based surveillance was conducted nationally in Finland and regionally
      in Canberra, Australia, western Sweden, and three areas in each of Canada and
      Denmark during 2000-2008. Incidence rates were age-standardized and gender
      standardized to the EU 27-country 2007 population. During 83 million person-years
      of surveillance, 18,430 episodes of S. aureus BSI were identified. The overall
      annual incidence rate for S. aureus BSI was 26.1 per 100,000 population, and
      those for methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S.
      aureus (MRSA) were 24.2 and 1.9 per 100,000, respectively. Although the overall
      incidence of community-onset MSSA BSI (15.0 per 100,000) was relatively similar
      across regions, the incidence rates of hospital-onset MSSA (9.2 per 100,000),
      community-onset MRSA (1.0 per 100,000) and hospital-onset MRSA (0.8 per 100,000)
      BSI varied substantially. Whereas the overall incidence of S. aureus BSI did not
      increase over the study period, there was an increase in the incidence of MRSA
      BSI. Major changes in the occurrence of community-onset and hospital-onset MSSA
      and MRSA BSI occurred, but these varied significantly among regions, even within
      the same country. Although major changes in the epidemiology of community-onset
      and hospital-onset MSSA and MRSA BSIs are occurring, this multinational
      population-based study did not find that the overall incidence of S. aureus BSI
      is increasing.

PMID- 22616818
TI  - Diagnostic accuracy of transrectal elastosonography (TRES) imaging for the
      diagnosis of prostate cancer: a systematic review and meta-analysis.
AB  - To assess the diagnostic performance of transrectal elastosonography (TRES) for
      the detection of prostate cancer. Two reviewers independently extracted the data
      from each study. Quality was assessed with a validated quality assessment tool
      for diagnostic accuracy studies. Diagnostic accuracy of TRES in relation to
      current standard references (transrectal ultrasonography [TRUS] biopsies and
      histopathology of radical prostatectomy [RP] specimens) was estimated. A
      bivariate random effects model was used to obtain sensitivity and specificity
      values. Hierarchical summary receiver operating characteristic (HSROC) were
      calculated. In all, 16 studies (2278 patients) were included in the review. Using
      histopathology of the RP specimen as reference standard, the pooled data of four
      studies showed that the sensitivity of TRES ranged between 0.71 to 0.82 and the
      specificity ranged between 0.60 to 0.95 (pooled diagnostic odds ratio [DOR] 19.6;
      95% confidence interval [CI] 7.7-50.03). The sensitivity varied from 0.26 to 0.87
      and specificity varied from 0.17 to 0.76 (pooled DOR 2.141; 95% CI 0.525 to 
      8.737) using TRUS biopsies (minimum of 10) as a reference standard. The quality
      of most studies was modest. SROC estimated 0.8653 area under the curve predicting
      high chances of detecting prostate cancer. There were no health economics or
      health-related quality of life of the participants reported in the studies and
      all the studies used compressional technique with no reported standardisation.
      The TRES technique appears to improve the detection of prostate cancer compared
      with systematic biopsy and shows a good accuracy in comparison with
      histopathology of the RP specimen. However, studies lacked standardisation of the
      technique, had poor quality of reporting and a large variation in the outcomes
      based on the reference standards and techniques used.

PMID- 22616819
TI  - Puberunine and puberudine, two new C18-diterpenoid alkaloids from Aconitum
      barbatum var. puberulum.
AB  - Two C(18)-diterpenoid alkaloids, puberunine (1) and puberudine (2), together with
      four other new alkaloids, including the first examples having beta-oriented
      substitution at C-3 and a rare chloro-substituent were isolated from Aconitum
      barbatum var. puberulum. Their structures were elucidated by spectroscopic
      methods. Puberunine and puberudine, which possess a unique rearranged E ring and
      an opened A ring, respectively, represent new subtypes of the C(18)-diterpenoid
      alkaloids. A plausible biosynthetic pathway of 1 and 2 was proposed.

PMID- 22616820
TI  - Subclinical iron deficiency is a silent epidemic amongst voluntary blood donors.

PMID- 22616821
TI  - Cryopreserved penile tunica albuginea for allotransplantation: a morphological
      and ultrastructural investigation.
AB  - INTRODUCTION: Peyronie's disease, a connective tissue disorder of penile tunica
      albuginea (TA) associated with penile deformity, curvature, pain, and erectile
      dysfunction, is best managed surgically, but suitable graft biomaterials are not
      available. AIM: To establish whether cryopreservation affects human TA in view of
      its use in allotransplants. METHODS: The effects on TA samples of the two most
      widely used tissue cryopreservation methods were investigated using an ad hoc
      panel of histochemical, immunohistochemical, and ultrastructural tests. Apoptotic
      cells were evaluated using the terminal deoxynucleotidyl transferase method of
      end labeling (TUNEL) assay. MAIN OUTCOME MEASURES: Assessment of tissue integrity
      and arrangement of collagen and elastic fibers in thawed TA. RESULTS: Both
      cryofixation methods provided TA tissue suitable for use as graft material.
      Significant ultrastructural changes, namely, a greater diameter of collagen
      fibrils, were detected in sections preserved in liquid nitrogen; nonetheless,
      such increase never exceeded the normal range. The comprehensive panel of assays
      used proved suitable to characterize the thawed tissue. CONCLUSION: Human TA is
      suitable for cryopreservation; freezing at -80  degrees C provides better results
      than preservation in liquid nitrogen.

PMID- 22616822
TI  - Distributing learning over time: the spacing effect in children's acquisition and
      generalization of science concepts.
AB  - The spacing effect describes the robust finding that long-term learning is
      promoted when learning events are spaced out in time rather than presented in
      immediate succession. Studies of the spacing effect have focused on memory
      processes rather than for other types of learning, such as the acquisition and
      generalization of new concepts. In this study, early elementary school children
      (5- to 7-year-olds; N = 36) were presented with science lessons on 1 of 3
      schedules: massed, clumped, and spaced. The results revealed that spacing lessons
      out in time resulted in higher generalization performance for both simple and
      complex concepts. Spaced learning schedules promote several types of learning,
      strengthening the implications of the spacing effect for educational practices
      and curriculum.

PMID- 22616824
TI  - Bilateral lung transplant for hereditary hemorrhagic telangiectasia in a
      pediatric patient.
AB  - HHT is an autosomal dominant vascular dysplasia, in which abnormalities of
      endothelial cells cause patients to develop mucocutaneous telangiectasias, and
      AVMs of the pulmonary, hepatic, and cerebral circulations. Pulmonary AVMs occur
      in more than 20% of patients with HHT, and presentation varies from simple
      diffuse telangiectasias to large complex structures. Surgical management is
      usually indicated for large pulmonary AVMs. Treatment options for pulmonary AVMs
      include therapeutic embolization, segmental or lobar resection of the affected
      lung, and less commonly lung transplantation. Here we report the first successful
      case of a bilateral lung transplant for a four-yr-old girl with HHT.

PMID- 22616825
TI  - Clinical features and immunohistochemical expression levels of androgen,
      estrogen, progesterone and Ki-67 receptors in relationship with gross-total
      resected meningiomas relapse.
AB  - OBJECTIVE: To investigate the recurrent risk factors of intracranial meningiomas
      after gross-total resection (Simpson II Grade). METHODS: We retrospectively
      analysed 162 meningiomas in the General Hospital of Shenyang Military Region and
      Changzheng Hospital in Shanghai China, which underwent nearly gross-total
      resection using microneurosurgery techniques from 2002 to 2007. Monofactorial and
      Cox regression statistics methods were carried out to analyse the relationship
      between the post-operation tumour relapse and some clinical features including
      the patient sex, age, tumour size, tumour shape, tumour pathological grade and
      the immunohistochemical expression levels of Ki-67, androgen receptor (AR),
      estrogen receptor (ER) and progesterone receptor (PR). RESULTS: There are 53
      recurrent meningiomas during the follow-up period. The recurrent rate is about
      32.7%. Immunohistochemistry results indicate that AR, ER, PR, Ki-67 are
      positively expressed on some tumour cell nuclear. Cox regression analysis reveals
      that tumour size, tumour shape, pathological grade and Ki-67 expression levels
      are significantly correlated with the tumour relapse (p <0.05). CONCLUSIONS: Our
      results demonstrate high recurrent rate for gross-total resection meningiomas.
      Tumour diameter exceeding 5 cm, irregular shape tumour, pathological grade II and
      III and positive expression of Ki-67 were the risk factors for post-operation
      meningioma relapse. The recurrent rate increases coincidentally with the follow
      up period.

PMID- 22616823
TI  - 18beta-glycyrrhetinic acid inhibits rotavirus replication in culture.
AB  - BACKGROUND: Glycyrrhizin (GA) and primary metabolite 18beta-glycyrrhetinic acid
      (GRA) are pharmacologically active components of the medicinal licorice root, and
      both have been shown to have antiviral and immunomodulatory properties. Although
      these properties are well established, the mechanisms of action are not
      completely understood. In this study, GA and GRA were tested for the ability to
      inhibit rotavirus replication in cell culture, toward a long term goal of
      discovering natural compounds that may complement existing vaccines. METHODS:
      Epithelial cells were treated with GA or GRA various times pre- or post-infection
      and virus yields were measured by immunofluorescent focus assay. Levels of viral
      proteins VP2, VP6, and NSP2 in GRA treated cells were measured by immunoblot to
      determine if there was an effect of GRA treatment on the accumulation of viral
      protein. RESULTS: GRA treatment reduced rotavirus yields by 99% when added to
      infected cultures post-- virus adsorption, whereas virus yields in GA treated
      cultures were similar to mock treated controls. Time of addition experiments
      indicated that GRA-mediated replication inhibition likely occurs at a step or
      steps subsequent to virus entry. The amounts of VP2, VP6 and NSP2 were
      substantially reduced when GRA was added to cultures up to two hours post-entry.
      CONCLUSIONS: GRA, but not GA, has significant antiviral activity against
      rotavirus replication in vitro, and studies to determine whether GRA attenuates
      rotavirus replication in vivo are underway.

PMID- 22616826
TI  - Living a demanding life--spouses' experiences of living with a person suffering
      from intermittent claudication.
AB  - AIM: To report a study of family members' experiences of living with a person
      suffering from intermittent claudication caused by peripheral arterial disease.
      BACKGROUND: Intermittent claudication is a symptom caused by peripheral arterial
      disease. Walking ability is reduced due to pain and this also affects the family
      members and leads to consequences such as isolation and a restricted life.
      DESIGN: This study has a qualitative descriptive design. METHODS: Ten spouses
      living with a person suffering from intermittent claudication were interviewed
      between December 2009-June 2010. The interviews were then analysed using
      qualitative thematic analysis. FINDINGS: Four themes were identified:
      'Frustrating to not meet intentions', 'Undergoing changes in social life', 'Being
      a person on the side of things' and 'Intertwining of circumstances'. The overall
      theme 'Living a demanding life' illustrates that intermittent claudication has
      great impact on daily life among spouses. CONCLUSION: This study gives an insight
      into the complexities and the difficulties of living together with someone
      suffering from intermittent claudication, a symptom that has great impact on both
      the spouses' and the ill persons' lives. According to the findings in this study,
      it is important to gain knowledge about the spouses' experiences because an
      holistic perspective is essential to treat and support the ill persons and their
      spouses.

PMID- 22616827
TI  - Food reward in the obese and after weight loss induced by calorie restriction and
      bariatric surgery.
AB  - Increased availability of tasty, energy-dense foods has been blamed as a major
      factor in the alarmingly high prevalence of obesity, diabetes, and metabolic
      disease, even in young age. A heated debate has started as to whether some of
      these foods should be considered addictive, similar to drugs and alcohol. One of
      the main arguments for food addiction is the similarity of the neural mechanisms
      underlying reward generation by foods and drugs. Here, we will discuss how food
      intake can generate reward and how behavioral and neural reward functions are
      different in obese subjects. Because most studies simply compare lean and obese
      subjects, it is not clear whether predisposing differences in reward functions
      cause overeating and weight gain, or whether repeated exposure or secondary
      effects of the obese state alter reward functions. While studies in both rodents
      and humans demonstrate preexisting differences in reward functions in the obese,
      studies in rodent models using calorie restriction and gastric bypass surgery
      show that some differences are reversible by weight loss and are therefore
      secondary to the obese state.

PMID- 22616828
TI  - Dual lectin-based size sorting strategy to enrich targeted N-glycopeptides by
      asymmetrical flow field-flow fractionation: profiling lung cancer biomarkers.
AB  - A dual lectin-based size sorting and simultaneous enrichment strategy for
      selectively isolating N-linked glycopeptides was developed using asymmetrical
      flow field-flow fractionation (AF4). AF4 is an elution-based method for
      separating biological macromolecules that has been utilized for the separation of
      lectin-glycopeptide complexes formed by mixing serum peptides with lectin
      cocktails according to the difference in diffusion coefficients. It has also been
      used for simultaneous depletion of nonglycosylated peptides. The dual lectin
      based enrichment method was applied to proteolytic peptides from lung cancer
      serum samples with two lectins (WGA, GlcNAc-specific, and SNA, Sia-specific), and
      the whole mixture was separated by AF4. The lectin-glycopeptide complex fractions
      collected during AF4 separation were endoglycosidically digested with PNGase F.
      The resulting deamidated glycopeptides were analyzed by nanoflow liquid
      chromatography-electrospray ionization-tandem mass spectrometry (nLC-ESI-MS-MS)
      to semiquantitatively profile the N-linked glycopeptides from the sera of lung
      cancer patients and healthy controls. The AF4 enrichment strategy coupled with
      nLC-ESI-MS-MS identified 16/24 (up/down-regulated by at least 10-fold compared to
      normal sera) N-linked glycopeptides from a WGA complex fraction of lung cancer
      sera and 18/3 from a SNA fraction.

PMID- 22616829
TI  - Septic shock--evaluating another failed treatment.

PMID- 22616831
TI  - Discrepancies between elderly patient's self-reported and prescribed medications:
      a social investigation.
AB  - AIMS: To study some characteristics of the elderly people attending the family
      practice clinic at the Jordan University Hospital (JUH) and to evaluate their
      knowledge of the prescribed drugs. METHODS: A total of 400 elderly people (180
      men and 220 women) aged 71 +/- 5.8 years were studied regarding sociodemographic
      characteristics and the use of medicinal and nonmedicinal remedies. In addition,
      agreement between self-reported drug information and information taken from the
      medical records was also evaluated. FINDINGS: Almost one-third of the patients
      had full agreement between their knowledge of total number of drugs they take and
      the numbers found in the medical records, whereas 43.4% underestimated and 21.8%
      overestimated these numbers. Five drugs/classes were accurately estimated by the
      patient (methyldopa, ezetimibe, warfarin, statins and antigout drugs).
      Underestimation was noticed in 17 drugs/classes and overestimation in 14. The
      significantly underestimated drug classes were biphoshponates, proton pump
      inhibitors, sulfonylureas and antiepileptic drugs. CONCLUSION: Some aspects of
      elderly people were evaluated regarding their medication knowledge. Almost two
      third of the patients did not take their drugs in the proper way. The results of
      the study highlight the importance of taking several actions by all healthcare
      workers and by the community to optimise health care provided for elderly people.

PMID- 22616832
TI  - Anxiety and chronic pain.
AB  - Questions from patients about pain conditions and analgesic pharmacotherapy and
      responses from authors are presented to help educate patients and make them more
      effective self-advocates. The topics addressed in this issue are pain-related
      anxiety, its symptoms, and possible treatment approaches.

PMID- 22616833
TI  - Ehlers-Danlos syndrome and chronic pain.
AB  - Questions from patients about pain conditions and analgesic pharmacotherapy and
      responses from authors are presented to help educate patients and make them more
      effective self-advocates. The topics addressed in this issue are Ehlers-Danlos
      syndrome and associated chronic pain; the information is meant to help readers
      understand the mechanisms for pain in this connective tissue disorder as well as
      general treatment principles for chronic pain management.

PMID- 22616834
TI  - On talking and touching in medicine.
AB  - Dr. Howard Brody, a leader in bioethics and medical humanities, describes how
      human touch impacts pain management outcomes. The symbolism of positive meaning
      versus negative meaning and how they effect patients' perception of pain are
      explored.

PMID- 22616835
TI  - Re: Ensuring patient access to essential medicines while minimizing harmful use:
      a revised World Health Organization tool to improve national drug control policy.
      Letter to the editor.

PMID- 22616830
TI  - Drotrecogin alfa (activated) in adults with septic shock.
AB  - BACKGROUND: There have been conflicting reports on the efficacy of recombinant
      human activated protein C, or drotrecogin alfa (activated) (DrotAA), for the
      treatment of patients with septic shock. METHODS: In this randomized, double
      blind, placebo-controlled, multicenter trial, we assigned 1697 patients with
      infection, systemic inflammation, and shock who were receiving fluids and
      vasopressors above a threshold dose for 4 hours to receive either DrotAA (at a
      dose of 24 MUg per kilogram of body weight per hour) or placebo for 96 hours. The
      primary outcome was death from any cause 28 days after randomization. RESULTS: At
      28 days, 223 of 846 patients (26.4%) in the DrotAA group and 202 of 834 (24.2%)
      in the placebo group had died (relative risk in the DrotAA group, 1.09; 95%
      confidence interval [CI], 0.92 to 1.28; P=0.31). At 90 days, 287 of 842 patients
      (34.1%) in the DrotAA group and 269 of 822 (32.7%) in the placebo group had died
      (relative risk, 1.04; 95% CI, 0.90 to 1.19; P=0.56). Among patients with severe
      protein C deficiency at baseline, 98 of 342 (28.7%) in the DrotAA group had died
      at 28 days, as compared with 102 of 331 (30.8%) in the placebo group (risk ratio,
      0.93; 95% CI, 0.74 to 1.17; P=0.54). Similarly, rates of death at 28 and 90 days
      were not significantly different in other predefined subgroups, including
      patients at increased risk for death. Serious bleeding during the treatment
      period occurred in 10 patients in the DrotAA group and 8 in the placebo group
      (P=0.81). CONCLUSIONS: DrotAA did not significantly reduce mortality at 28 or 90
      days, as compared with placebo, in patients with septic shock. (Funded by Eli
      Lilly; PROWESS-SHOCK ClinicalTrials.gov number, NCT00604214.).

PMID- 22616836
TI  - "Contact" of nanoscale stiff films.
AB  - We investigated the contact behaviors of a nanoscopic stiff thin film bonded to a
      compliant substrate and derived an analytical solution for determining the
      elastic modulus of thin films. Microscopic contact deformations of the gold and
      polydopamine thin films (<200 nm) coated on polydimethylsiloxane elastomers were
      measured by indenting a soft tip and analyzed in the framework of the classical
      plate theory and Johnson-Kendall-Roberts (JKR) contact mechanics. The analysis of
      this thin film contact mechanics focused on the bending and stretching resistance
      of thin films and is fundamentally different from conventional indentation
      measurements where the focus is on the fracture and compression of the films. The
      analytical solution of the elastic modulus of nanoscopic thin films was validated
      experimentally using 50 and 100 nm gold thin films coated on polydimethylsiloxane
      elastomers. The technical application of this analysis was further demonstrated
      by measuring the elastic modulus of thin films of polydopamine, a recently
      discovered biomimetic universal coating material. Furthermore, the method
      presented here is able to quantify the contact behaviors of nanoscopic thin
      films, effectively providing fundamental design parameters, the elastic modulus,
      and the work of adhesion, crucial for transferring them effectively into
      practical applications.

PMID- 22616837
TI  - TNF-related apoptosis-inducing ligand significantly attenuates metabolic
      abnormalities in high-fat-fed mice reducing adiposity and systemic inflammation.
AB  - TRAIL [TNF (tumour necrosis factor)-related apoptosis-inducing ligand] has
      recently been shown to ameliorate the natural history of DM (diabetes mellitus).
      It has not been determined yet whether systemic TRAIL delivery would prevent the
      metabolic abnormalities due to an HFD [HF (high-fat) diet]. For this purpose, 27
      male C57bl6 mice aged 8 weeks were randomly fed on a standard diet, HFD or
      HFD+TRAIL for 12 weeks. TRAIL was delivered weekly by intraperitoneal injection.
      Body composition was evaluated; indirect calorimetry studies, GTT (glucose
      tolerance test) and ITT (insulin tolerance test) were performed. Pro-inflammatory
      cytokines, together with adipose tissue gene expression and apoptosis, were
      measured. TRAIL treatment reduced significantly the increased adiposity
      associated with an HFD. Moreover, it reduced significantly hyperglycaemia and
      hyperinsulinaemia during a GTT and it improved significantly the peripheral
      response to insulin. TRAIL reversed the changes in substrate utilization induced
      by the HFD and ameliorated skeletal muscle non-esterified fatty acids oxidation
      rate. This was associated with a significant reduction of pro-inflammatory
      cytokines together with a modulation of adipose tissue gene expression and
      apoptosis. These findings shed light on the possible anti-adipogenic and anti
      inflammatory effects of TRAIL and open new therapeutic possibilities against
      obesity, systemic inflammation and T2DM (Type 2 DM).

PMID- 22616839
TI  - Single non-ionic surfactant based self-nanoemulsifying drug delivery systems:
      formulation, characterization, cytotoxicity and permeability enhancement study.
AB  - Single non-ionic surfactant based self-nanoemulsifying drug delivery system
      (SNEDDS) was formulated and characterised for poor water soluble drug,
      Atorvastatin calcium. Capmul MCM oil showing highest solubility for Atorvastatin
      calcium was selected as oil phase. Self-nanoemulsifying capacity of Cremophor RH
      40, Cremophor EL, Tween 20, Tween 60, Tween 80 and Labrasol were tested for the
      selected oil. In vitro dissolution studies were performed and were characterized
      by t85% and dissolution efficiency (DE). Cytotoxicity of the formulations and
      permeation enhancement of the drug across caco-2 cell monolayer was assessed.
      Capmul MCM was found to be better nanoemulsified in decreasing order of Cremophor
      RH 40 > Cremophor EL > Tween 20 > Tween 60 > Tween 80. Values of droplet size
      (range 11-83 nm), polydispersity index (range 0.07-0.65); zeta potential (range 
      3.97 to -19.0) and cloud point (60-85 degrees C) before and after drug loading
      proves the uniformity and stability of the formulations. SNEDDS formulated with
      Tween 20 surfactant showed enhanced dissolution with t85% and DE values at 10 min
      and 78.70, respectively. None of the formulation showed cytotoxicity at the
      concentration tested. Tween 20 based SNEDDS enhanced permeation of the drug as
      compared with pure drug across cell lines. It can be concluded that SNEDDS can be
      formulated by using single non-ionic surfactant system for enhance dissolution
      and absorption of poorly soluble drug, Atorvastatin calcium.

PMID- 22616838
TI  - Characterization of refined edible oils enriched with phenolic extracts from
      olive leaves and pomace.
AB  - Refined edible oils (viz., oils from maize, soya, high-oleic sunflower,
      sunflower, olive, and rapeseed) enriched at two concentration levels (200 and 400
      MUg/mL total phenolic content) with phenolic extracts isolated from olive pomace
      and leaves have been characterized and compared with nonenriched oils and extra
      virgin olive oil (EVOO). Enriched oils were analyzed by LC-TOF/MS to generate
      representative fingerprints and compared with nonenriched oils and EVOO by
      unsupervised principal component analysis (PCA). The two raw materials reported
      enriched oils with profiles which were compared with those provided by EVOOs.
      Correlation analysis enabled us to establish the enriched oils with a composition
      more similar to EVOO. Discrimination according to the enrichment level depended
      on the raw material for extracts, and a global discussion about the enrichment on
      relevant phenolic compounds present in EVOO has reported quantitative results
      concerning the enrichment level for those significant compounds with known
      nutraceutical properties. 

PMID- 22616840
TI  - Decision making in pretransplant nephrectomy for polycystic kidneys, is it valid
      for horseshoe kidneys?

PMID- 22616841
TI  - Magic angle spinning and oriented sample solid-state NMR structural restraints
      combine for influenza a M2 protein functional insights.
AB  - As a small tetrameric helical membrane protein, the M2 proton channel structure
      is highly sensitive to its environment. As a result, structural data from a lipid
      bilayer environment have proven to be essential for describing the conductance
      mechanism. While oriented sample solid-state NMR has provided a high-resolution
      backbone structure in lipid bilayers, quaternary packing of the helices and many
      of the side-chain conformations have been poorly restrained. Furthermore, the
      quaternary structural stability has remained a mystery. Here, the isotropic
      chemical shift data and interhelical cross peaks from magic angle spinning solid
      state NMR of a liposomal preparation strongly support the quaternary structure of
      the transmembrane helical bundle as a dimer-of-dimers structure. The data also
      explain how the tetrameric stability is enhanced once two charges are absorbed by
      the His37 tetrad prior to activation of this proton channel. The combination of
      these two solid-state NMR techniques appears to be a powerful approach for
      characterizing helical membrane protein structure.

PMID- 22616842
TI  - Zeroing of six-component handrim dynamometer for biomechanical studies of manual
      wheelchair locomotion.
AB  - A six-component handrim dynamometer (HRD) is a dynamometer that rotates around
      the wheel axle during measurements. For this kind of dynamometer, static zero
      level calibration is insufficient because the proportion of the forces (i.e.
      handrim weight and centrifugal force) measured by each sensor varies according to
      the angular position and velocity of the dynamometer. The dynamic calibration
      presented in this paper is based on the direct correction of the sensor signals
      using Fourier's polynomials that take into account the influences of both the
      handrim weight distribution on the sensors with respect to the wheel's angular
      position and the effect of the wheel's angular velocity. When these corrections
      were applied to the signals produced by the sensors while the HRD was rotating
      and no effort was being exerted on the handrim, the calculated forces and torques
      remained close to zero, as expected. Based on these results, the wheel
      dynamometer can be confidently used for studying manual wheelchair locomotion
      under various real conditions. The method could also be applied in other
      situations in which a dynamometer rotates during measurements.

PMID- 22616843
TI  - Effect and therapeutic mechanisms of tonsillectomy for childhood IgA nephropathy.
AB  - AIM: We investigated efficacy and therapeutic mechanisms of tonsillectomy for
      intractable childhood IgA nephropathy. Five patients refused tonsillectomy. Among
      25 patients, 19 patients were able to evaluate histological findings before and
      after surgery. Patients with poor (n = 7) or relatively poor (n = 18)
      histologically determined prognosis and an age of at least 7 years, together with
      proteinuria of at least 0.3 g/day or severe persisting despite ongoing drug
      treatment, are candidates for surgery. Patients were grouped by interval between
      diagnosis of IgA nephropathy and tonsillectomy (within 3 years; early group vs 3
      years or later; later group). Patients underwent kidney biopsy shortly before and
      1 to 2 years after tonsillectomy. RESULTS: Proteinuria was reduced after
      tonsillectomy over 2 years of follow-up in both early and later groups compared
      with proteinuria in the 6 months preceding surgery. Complete remission was
      achieved in 10 patients, most often among those having surgery within 3 years,
      while patients refusing surgery failed to attain complete remission of urinary
      findings. Histological activity decreased in both groups, significantly when
      surgery was early. Complement component C3 deposition and activated macrophages
      in glomeruli decreased after tonsillectomy, especially with early surgery.
      CONCLUSION: Tonsillectomy improved clinicopathological features in relatively
      severe paediatric IgA nephropathy, especially with the early-surgery group.
      Therapeutic mechanisms may include inhibition of complement activity in glomeruli
      and glomerular infiltration by activated macrophages.

PMID- 22616844
TI  - Base-assisted one-pot synthesis of N,N',N"-triaryltriazatriangulenium dyes:
      enhanced fluorescence efficiency by steric constraints.
AB  - In this paper we report the first synthesis of cationic N,N',N"
      triaryltriazatriangulenium dyes (Ar(3)-TATA(+)). Previously, only alkyl
      substituted triazatriangulenium derivatives (R(3)-TATA(+)) were known, a
      consequence of the low reactivity of anilines in the aromatic nucleophilic
      substitution reaction leading to the formation of the TATA(+) core. The synthesis
      of Ar(3)-TATA(+) was achieved by heating the tris(2,6-dimethoxyphenyl)methylium
      ion (DMP(3)C(+)) in various anilines in the presence of NaH. In the solvent-free
      reaction all three aryl substituents could be introduced despite the low
      reactivity of the anilines. The symmetric Ar(3)-TATA(+) derivatives with Ar =
      phenyl (2), 4-methoxyphenyl (3), and 4-bromophenyl (4) were synthesized. Single
      crystal structures of 2 and 4 were obtained as BF(4)(-) salts, where torsional
      angles larger than 80 degrees  were observed between the TATA(+) chromophore and
      the aryl substituents. The photophysical properties were studied in solution and
      in thin films. The results show that the Ar(3)-TATA(+) dyes have a surprising 3
      fold increase in fluorescence quantum yields when compared to the parent alkyl
      substituted R(3)-TATA(+) salts. With a high quantum yield (>50%) and emission in
      the red (lambda(fl) = 560 nm) the Ar(3)-TATA(+) dyes represent a promising new
      addition to the family of superstable cationic triangulenium dyes. Additionally,
      the synthesized tribromo derivative 4 is shown to be a potential triagonal
      synthon for polymers and other macromolecules.

PMID- 22616845
TI  - Mechanisms of tracheal filling in insects.
AB  - Insects exchange respiratory gases primarily using tracheal systems that are
      filled with gas. However, in different developmental and environmental
      circumstances, liquid can occupy the tracheal system, which can significantly
      impair its respiratory function. Insects therefore use a suite of mechanisms for
      tracheal filling, which is the process of replacing tracheal liquids with gas. We
      review these mechanisms for liquid removal and gas filling. By integrating recent
      molecular work with older physiological literature, we show that liquid removal
      likely involves active ion transport in the whole tracheal system. Gas filling
      reveals fascinating interactions between geometry, surface chemistry of the
      tracheal walls, the tracheal liquid, and dissolved gases. The temporal proximity
      to moulting allows for potentially complex interdependencies between gas filling,
      moult-associated hormone signaling, and cuticle sclerotization. We propose a
      mechanistic model for tracheal filling. However, because the composition of the
      liquid is unknown, it remains hypothetical.

PMID- 22616847
TI  - Organic stealth nanoparticles for highly effective in vivo near-infrared
      photothermal therapy of cancer.
AB  - In recent years, a wide range of near-infrared (NIR) light absorbing
      nanomaterials, mostly inorganic ones, have been developed for photothermal
      therapy (PTT) of cancer. In this work, we develop a novel organic PTT agent based
      on poly-(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) (PEDOT:PSS), a
      conductive polymer mixture with strong NIR absorbance, for in vivo photothermal
      treatment of cancer. After being layer-by-layer coated with charged polymers and
      then conjugated with branched polyethylene glycol (PEG), the obtained PEDOT:PSS
      PEG nanoparticles are highly stable in the physiological environment and exhibit
      a stealth-like behavior after intravenous injection with a long blood circulation
      half-life. As a result, an extremely high in vivo tumor uptake of PEDOT:PSS-PEG
      attributed to the tumor-enhanced permeability and retention effect is observed.
      We further use PEDOT:PSS-PEG as a PTT agent for in vivo cancer treatment and
      realize excellent therapeutic efficacy in a mouse tumor model under NIR light
      irradiation at a low laser power density. Comprehensive blood tests and careful
      histological examination reveal no apparent toxicity of PEDOT:PSS-PEG to mice at
      our treated dose within 40 days. To our best knowledge, this work is the first to
      use systemically administrated conductive polymer nanoparticles for highly
      effective in vivo PTT treatment in animals and encourages further explorations of
      those organic nanomaterials for cancer theranostic applications.

PMID- 22616846
TI  - Limited effect of anti-rheumatic treatment on 15-prostaglandin dehydrogenase in
      rheumatoid arthritis synovial tissue.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory disease in
      which prostaglandin E2 (PGE2) displays an important pathogenic role. The enzymes
      involved in its synthesis are highly expressed in the inflamed synovium, while
      little is known about 15- prostaglandin dehydrogenase (15-PGDH) that metabolizes
      PGE2. Here we aimed to evaluate the localization of 15-PGDH in the synovial
      tissue of healthy individuals or patients with inflammatory arthritis and
      determine the influence of common RA therapy on its expression. METHODS: Synovial
      tissue specimens from healthy individuals, psoriatic arthritis, ostheoarthritis
      and RA patients were immunohistochemically stained to describe the expression
      pattern of 15-PGDH. In addition, the degree of enzyme staining was evaluated by
      computer analysis on stained synovial biopsies from two groups of RA patients,
      before and after RA specific treatment with either intra-articular
      glucocorticoids or oral methotrexate therapy. Prostaglandins derived from the
      cyclooxygenase (COX) pathway were determined by liquid-chromatography mass
      spectrometry in supernatants from interleukin (IL) 1beta-activated fibroblast
      like synoviocytes (FLS) treated with methotrexate. RESULTS: 15-PGDH was present
      in healthy and inflamed synovial tissue, mainly in lining macrophages,
      fibroblasts and vessels. Intra-articular glucocorticoids showed a trend towards
      reduced 15-PGDH expression in RA synovium (p = 0.08) while methotrexate treatment
      left the PGE2 pathway unaltered both in biopsies ex vivo and in cultured FLS.
      CONCLUSIONS: Early methotrexate therapy has little influence on the expression of
      15-PGDH and on any of the PGE2 synthesizing enzymes or COX-derived metabolites.
      Thus therapeutic strategies involving blocking induced PGE2 synthesis may find a
      rationale in additionally reducing local inflammatory mediators.

PMID- 22616848
TI  - Epidemiological study of complementary and alternative medicine (CAM) use for the
      improvement of sexual function in young Korean men: the Korean Internet Sexuality
      Survey (KISS), part II.
AB  - INTRODUCTION: Few studies have been conducted on complementary and alternative
      medicine (CAM) for improving sexual function. AIMS: We investigate CAM use for
      improving sexual function and propose a model explaining what leads to CAM use.
      METHODS: Participants between 20 and 59 years old were recruited from an Internet
      research panel representing young Korean men. Participants were asked to complete
      questionnaires on demographic details, attitude toward sexual activity, sexual
      function, CAM use, and desire to use CAM. Subjects were classified into three
      subgroups. Men who use CAM, men who desire but do not actually use CAM, and men
      who neither use nor desire to use CAM were allocated to groups A (actual user), P
      (potential user), and N (nonuser), respectively. MAIN OUTCOME MEASURES: CAM use,
      desire to use CAM, questionnaires on self-reported sexual function and attitude
      toward sexual activity, International Index of Erectile Function-5, Premature
      Ejaculation Diagnostic Tool, and Short Form 36 Health Survey (SF-36). RESULTS:
      Among 443 subjects with a mean age of 39.2 +/- 10.2 years, 49 (11.1%) used CAM
      for improving sexual function (group A). Dietary supplements were most commonly
      used. Overall mean satisfaction for the used CAM was 55.5 +/- 24.2%. There were
      192 (43.3%) men who desired but did not use CAM (group P). According to
      multivariate analysis, risk factors for desiring CAM included drinking (odds
      ratio [OR] = 2.24, 95% confidence interval [CI] = 1.28-3.91), regarding sex a
      very important part of life (OR = 2.16; 95% CI = 1.41-4.09), self-reported
      erectile dysfunction (ED) (OR = 5.08; 95% CI = 1.60-16.1), and self-reported
      premature ejaculation (PE) (OR = 3.34; 95% CI = 1.65-6.76). Risk factors for
      actual CAM use included smoking (OR = 2.49; 95% CI = 1.11-5.61), a strongly
      positive attitude toward sexual activity (OR = 3.77; 95% CI = 1.42-9.99), low
      role emotion points on the SF-36 (OR = 0.98; 95% CI = 0.97-0.99), and self
      reported non-PE (OR = 0.22; 95% CI = 0.06-0.73). CONCLUSIONS: Smoking, drinking,
      self-reported ED, self-reported PE, attitude toward sexual activity, and
      emotional problems play roles in making decisions concerning CAM use.

PMID- 22616849
TI  - Role of JNK isoforms in the development of neuropathic pain following sciatic
      nerve transection in the mouse.
AB  - BACKGROUND: Current tools for analgesia are often only partially successful, thus
      investigations of new targets for pain therapy stimulate great interest.
      Consequent to peripheral nerve injury, c-Jun N-terminal kinase (JNK) activity in
      cells of the dorsal root ganglia (DRGs) and spinal cord is involved in triggering
      neuropathic pain. However, the relative contribution of distinct JNK isoforms is
      unclear. Using knockout mice for single isoforms, and blockade of JNK activity by
      a peptide inhibitor, we have used behavioral tests to analyze the contribution of
      JNK in the development of neuropathic pain after unilateral sciatic nerve
      transection. In addition, immunohistochemical labelling for the growth associated
      protein (GAP)-43 and Calcitonin Gene Related Peptide (CGRP) in DRGs was used to
      relate injury related compensatory growth to altered sensory function. RESULTS:
      Peripheral nerve injury produced pain-related behavior on the ipsilateral
      hindpaw, accompanied by an increase in the percentage of GAP43-immunoreactive
      (IR) neurons and a decrease in the percentage of CGRP-IR neurons in the lumbar
      DRGs. The JNK inhibitor, D-JNKI-1, successfully modulated the effects of the
      sciatic nerve transection. The onset of neuropathic pain was not prevented by the
      deletion of a single JNK isoform, leading us to conclude that all JNK isoforms
      collectively contribute to maintain neuropathy. Autotomy behavior, typically
      induced by sciatic nerve axotomy, was absent in both the JNK1 and JNK3 knockout
      mice. CONCLUSIONS: JNK signaling plays an important role in regulating pain
      threshold: the inhibition of all of the JNK isoforms prevents the onset of
      neuropathic pain, while the deletion of a single splice JNK isoform mitigates
      established sensory abnormalities. JNK inactivation also has an effect on axonal
      sprouting following peripheral nerve injury.

PMID- 22616850
TI  - Dissection of events in the resistance to beta-lactam antibiotics mediated by the
      protein BlaR1 from Staphylococcus aureus.
AB  - A heterologous expression system was used to evaluate activation of BlaR1, a
      sensor/signal transducer protein of Staphylococcus aureus with a central role in
      resistance to beta-lactam antibiotics. In the absence of other S. aureus proteins
      that might respond to antibiotics and participate in signal transduction events,
      we documented that BlaR1 fragmentation is autolytic, that it occurs in the
      absence of antibiotics, and that BlaR1 directly degrades BlaI, the gene repressor
      of the system. Furthermore, we disclosed that this proteolytic activity is metal
      ion-dependent and that it is not modulated directly by acylation of the sensor
      domain by beta-lactam antibiotics.

PMID- 22616851
TI  - Free-energy and structural analysis of ion solvation and contact ion-pair
      formation of Li(+) with BF4(-) and PF6(-) in water and carbonate solvents.
AB  - Free energy of contact ion-pair (CIP) formation of lithium ion with BF(4)(-) and
      PF(6)(-) in water, propylene carbonate (PC), dimethyl carbonate (DMC) are
      quantitatively analyzed using MD simulations combined with the energy
      representation method. The relative stabilities of the mono-, bi-, and tridentate
      coordination structures are assessed with and without solvent, and water, PC, and
      DMC are found to favor the CIP-solvent contact. The monodentate structure is
      typically most stable in these solvents, whereas the configuration is
      multidentate in vacuum. The free energy of CIP formation is not simply governed
      by the solvent dielectric constant, and microscopic analyses of solute-solvent
      interaction at a molecular level are then performed from energetic and structural
      viewpoints. Vacant sites of Li(+) cation in CIP are solvated with three carbonyl
      oxygen atoms of PC and DMC solvent molecules, and the solvation is stronger for
      the monodentate CIP than for the multidentate. Energetically favorable solute
      solvent configurations are shown to be spatially more restricted for the
      multidentate CIP, leading to the observation that the solvent favors the
      monodentate coordination structure.

PMID- 22616852
TI  - Brain tissue oxygen monitoring and hyperoxic treatment in patients with traumatic
      brain injury.
AB  - Cerebral ischemia is a well-recognized contributor to high morbidity and
      mortality after traumatic brain injury (TBI). Standard of care treatment aims to
      maintain a sufficient oxygen supply to the brain by avoiding increased
      intracranial pressure (ICP) and ensuring a sufficient cerebral perfusion pressure
      (CPP). Devices allowing direct assessment of brain tissue oxygenation have showed
      promising results in clinical studies, and their use was implemented in the Brain
      Trauma Foundation Guidelines for the treatment of TBI patients in 2007. Results
      of several studies suggest that a brain tissue oxygen-directed therapy guided by
      these monitors may contribute to reduced mortality and improved outcome of TBI
      patients. Whether increasing the oxygen supply to supraphysiological levels has
      beneficial or detrimental effects on TBI patients has been a matter of debate for
      decades. The results of trials of hyperbaric oxygenation (HBO) have failed to
      show a benefit, but renewed interest in normobaric hyperoxia (NBO) in the
      treatment of TBI patients has emerged in recent years. With the increased
      availability of advanced neuromonitoring devices such as brain tissue oxygen
      monitors, it was shown that some patients might benefit from this therapeutic
      approach. In this article, we review the pathophysiological rationale and
      technical modalities of brain tissue oxygen monitors, as well as its use in
      studies of brain tissue oxygen-directed therapy. Furthermore, we analyze
      hyperoxia as a treatment option in TBI patients, summarize the results of
      clinical trials, and give insights into the recent findings of hyperoxic effects
      on cerebral metabolism after TBI.

PMID- 22616853
TI  - Controlled-release melatonin, singly and combined with cognitive behavioural
      therapy, for persistent insomnia in children with autism spectrum disorders: a
      randomized placebo-controlled trial.
AB  - Although melatonin and cognitive-behavioural therapy have shown efficacy in
      treating sleep disorders in children with autism spectrum disorders, little is
      known about their relative or combined efficacy. One hundred and sixty children
      with autism spectrum disorders, aged 4-10 years, suffering from sleep onset
      insomnia and impaired sleep maintenance, were assigned randomly to either (1)
      combination of controlled-release melatonin and cognitive-behavioural therapy;
      (2) controlled-release melatonin; (3) four sessions of cognitive-behavioural
      therapy; or (4) placebo drug treatment condition for 12 weeks in a 1 : 1 : 1 : 1
      ratio. Children were studied at baseline and after 12 weeks of treatment.
      Treatment response was assessed with 1-week actigraphic monitoring, sleep diary
      and sleep questionnaire. Main outcome measures, derived actigraphically, were
      sleep latency, total sleep time, wake after sleep onset and number of awakenings.
      The active treatment groups all resulted in improvements across all outcome
      measures, with moderate-to-large effect sizes from baseline to a 12-week
      assessment. Melatonin treatment was mainly effective in reducing insomnia
      symptoms, while cognitive-behavioural therapy had a light positive impact mainly
      on sleep latency, suggesting that some behavioural aspects might play a role in
      determining initial insomnia. The combination treatment group showed a trend to
      outperform other active treatment groups, with fewer dropouts and a greater
      proportion of treatment responders achieving clinically significant changes
      (63.38% normative sleep efficiency criterion of >85% and 84.62%, sleep onset
      latency <30 min). This study demonstrates that adding behavioural intervention to
      melatonin treatment seems to result in a better treatment response, at least in
      the short term.

PMID- 22616854
TI  - Determinants of brachial-ankle pulse wave velocity in a Japanese population: a
      cohort study.
AB  - Arterial stiffness is one of the biggest predictors of coronary heart disease
      (CHD). We evaluated whether brachial-ankle pulse wave velocity (baPWV) and
      augmentation index (AI) are correlated with risk factors of CHD. All of the 528
      participants (270 males and 258 females) in this study were healthy workers aged
      from 36 to 69 (mean age: 47.9 +/- 8.1 years). The Framingham Risk Score (FRS)
      showed a good correlation with baPWV (r = 0.53, p < 0.01), indicating that FRS is
      also applicable as an index of arterial stiffness in Japanese people. Blood
      pressures were well controlled in patients with medical treatment for
      hypertension; however, vessels remained relatively still stiff, whereas the AI
      was considerably low. Multivariate linear regression analysis showed that factors
      of such as FRS, body mass index, alcohol consumption and AI P75 were
      significantly correlated with baPWV.

PMID- 22616855
TI  - Parenting under pressure: a grounded theory of parenting young children with life
      threatening congenital heart disease.
AB  - AIM: To report a grounded theory study to describe the process of parenting young
      children who have survived hypoplastic left heart syndrome to inform parent
      focused interventions. BACKGROUND: Technological advances in paediatric
      cardiology worldwide have improved the survival rates for young children with
      hypoplastic left heart syndrome who undergo staged surgical palliation. These
      children, however, are at risk for life-threatening complications and parents are
      charged with the responsibility to monitor their children at home with minimal
      support and guidance from healthcare professionals once home. DESIGN: A
      constructivist grounded theory study. METHOD: The study was conducted in 2006
      2008. Participants were 25 parents (15 mothers, 10 fathers) and 28 grandparents
      (17 grandmothers, 11 grandfathers) of 15 young children (6 months-4.5 years) who
      had undergone the Sano surgical approach for hypoplastic left heart syndrome. The
      53 interviews were digitally recorded, transcribed and analysed using open and
      focused coding, constant comparative analysis and memoing. FINDINGS: A process of
      Parenting under Pressure emerged that was characterized by four overlapping and
      re-emerging phases: (1) realizing and adjusting to the inconceivable; (2) growing
      increasingly attached; (3) watching for and accommodating the unexpected; and (4)
      encountering new challenges. CONCLUSIONS: In-depth understanding of the phases of
      Parenting under Pressure provides direction for nurses to support parents of
      children who survive hypoplastic left heart syndrome. Interventions that help
      carers of children with complex health conditions move through the phases of our
      Parenting under Pressure process may help them safeguard the survival of their
      children, and their own survival as parents as they manage multiple demands.

PMID- 22616856
TI  - Variable reference alignment: an improved peak alignment protocol for NMR
      spectral data with large intersample variation.
AB  - In an effort to address the variable correspondence problem across large sample
      cohorts common in metabolomic/metabonomic studies, we have developed a
      prealignment protocol that aims to generate spectral segments sharing a common
      target spectrum. Under the assumption that a single reference spectrum will not
      correctly represent all spectra of a data set, the goal of this approach is to
      perform local alignment corrections on spectral regions which share a common
      "most similar" spectrum. A natural beneficial outcome of this procedure is the
      automatic definition of spectral segments, a feature that is not common to all
      alignment methods. This protocol is shown to specifically improve the quality of
      alignment in (1)H NMR data sets exhibiting large intersample compositional
      variation (e.g., pH, ionic strength). As a proof-of-principle demonstration, we
      have utilized two recently developed alignment algorithms specific to NMR data,
      recursive segment-wise peak alignment and interval correlated shifting, and
      applied them to two data sets composed of 15 aqueous cell line extract and 20
      human urine (1)H NMR profiles. Application of this protocol represents a
      fundamental shift from current alignment methodologies that seek to correct
      misalignments utilizing a single representative spectrum, with the added benefit
      that it can be appended to any alignment algorithm.

PMID- 22616857
TI  - The emergence of protein complexes: quaternary structure, dynamics and allostery.
      Colworth Medal Lecture.
AB  - All proteins require physical interactions with other proteins in order to
      perform their functions. Most of them oligomerize into homomers, and a vast
      majority of these homomers interact with other proteins, at least part of the
      time, forming transient or obligate heteromers. In the present paper, we review
      the structural, biophysical and evolutionary aspects of these protein
      interactions. We discuss how protein function and stability benefit from
      oligomerization, as well as evolutionary pathways by which oligomers emerge,
      mostly from the perspective of homomers. Finally, we emphasize the specificities
      of heteromeric complexes and their structure and evolution. We also discuss two
      analytical approaches increasingly being used to study protein structures as well
      as their interactions. First, we review the use of the biological networks and
      graph theory for analysis of protein interactions and structure. Secondly, we
      discuss recent advances in techniques for detecting correlated mutations, with
      the emphasis on their role in identifying pathways of allosteric communication.

PMID- 22616858
TI  - Exploring the biochemistry at the extracellular redox frontier of bacterial
      mineral Fe(III) respiration.
AB  - Many species of the bacterial Shewanella genus are notable for their ability to
      respire in anoxic environments utilizing insoluble minerals of Fe(III) and Mn(IV)
      as extracellular electron acceptors. In Shewanella oneidensis, the process is
      dependent on the decahaem electron-transport proteins that lie at the
      extracellular face of the outer membrane where they can contact the insoluble
      mineral substrates. These extracellular proteins are charged with electrons
      provided by an inter-membrane electron-transfer pathway that links the
      extracellular face of the outer membrane with the inner cytoplasmic membrane and
      thereby intracellular electron sources. In the present paper, we consider the
      common structural features of two of these outer-membrane decahaem cytochromes,
      MtrC and MtrF, and bring this together with biochemical, spectroscopic and
      voltammetric data to identify common and distinct properties of these
      prototypical members of different clades of the outer-membrane decahaem
      cytochrome superfamily.

PMID- 22616859
TI  - Redox, haem and CO in enzymatic catalysis and regulation.
AB  - The present paper describes general principles of redox catalysis and redox
      regulation in two diverse systems. The first is microbial metabolism of CO by the
      Wood-Ljungdahl pathway, which involves the conversion of CO or H2/CO2 into acetyl
      CoA, which then serves as a source of ATP and cell carbon. The focus is on two
      enzymes that make and utilize CO, CODH (carbon monoxide dehydrogenase) and ACS
      (acetyl-CoA synthase). In this pathway, CODH converts CO2 into CO and ACS
      generates acetyl-CoA in a reaction involving Ni.CO, methyl-Ni and acetyl-Ni as
      catalytic intermediates. A 70 A (1 A=0.1 nm) channel guides CO, generated at the
      active site of CODH, to a CO 'cage' near the ACS active site to sequester this
      reactive species and assure its rapid availability to participate in a
      kinetically coupled reaction with an unstable Ni(I) state that was recently
      trapped by photolytic, rapid kinetic and spectroscopic studies. The present paper
      also describes studies of two haem-regulated systems that involve a principle of
      metabolic regulation interlinking redox, haem and CO. Recent studies with HO2
      (haem oxygenase-2), a K+ ion channel (the BK channel) and a nuclear receptor (Rev
      Erb) demonstrate that this mode of regulation involves a thiol-disulfide redox
      switch that regulates haem binding and that gas signalling molecules (CO and NO)
      modulate the effect of haem.

PMID- 22616860
TI  - Tryptophan oxygenation: mechanistic considerations.
AB  - From a protein structural viewpoint, tryptophan is often considered an inert
      structural amino acid, playing a role as a hydrophobic anchor in membrane
      proteins or as part of the hydrophobic core of soluble proteins. However,
      tryptophan is the only polyaromatic amino acid and, from a chemical viewpoint,
      possesses unique reactivity owing to the electron-richness of the indole system.
      This reactivity is seen in the area of natural products and metabolites which
      have exquisite modifications of the indole ring system. Enzymes have evolved
      multiple strategies to break or modify the indole ring; one particular class is
      the IDO/TDO (indoleamine/tryptophan dioxygenase) superfamily. A new member of
      this family, PrnB, on the surface catalyses a very different reaction, but
      actually shares much of the early chemistry with the tryptophan dioxygenases.
      Studies on PrnB have contributed to our understanding of the wider superfamily.
      In the present mini-review, recent developments in our understanding of how the
      TDO class of enzymes use activated molecular oxygen to break the indole ring are
      discussed.

PMID- 22616861
TI  - Protein dynamics and enzyme catalysis: the ghost in the machine?
AB  - One of the most controversial questions in enzymology today is whether protein
      dynamics are significant in enzyme catalysis. A particular issue in these debates
      is the unusual temperature-dependence of some kinetic isotope effects for enzyme
      catalysed reactions. In the present paper, we review our recent model [Glowacki,
      Harvey and Mulholland (2012) Nat. Chem. 4, 169-176] that is capable of
      reproducing intriguing temperature-dependences of enzyme reactions involving
      significant quantum tunnelling. This model relies on treating multiple
      conformations of the enzyme-substrate complex. The results show that direct
      'driving' motions of proteins are not necessary to explain experimental
      observations, and show that enzyme reactivity can be understood and accounted for
      in the framework of transition state theory.

PMID- 22616862
TI  - The prototypic class Ia ribonucleotide reductase from Escherichia coli: still
      surprising after all these years.
AB  - RNRs (ribonucleotide reductases) are key players in nucleic acid metabolism,
      converting ribonucleotides into deoxyribonucleotides. As such, they maintain the
      intracellular balance of deoxyribonucleotides to ensure the fidelity of DNA
      replication and repair. The best-studied RNR is the class Ia enzyme from
      Escherichia coli, which employs two subunits to catalyse its radical-based
      reaction: beta2 houses the diferric-tyrosyl radical cofactor, and alpha2 contains
      the active site. Recent applications of biophysical methods to the study of this
      RNR have revealed the importance of oligomeric state to overall enzyme activity
      and suggest that unprecedented subunit configurations are in play. Although it
      has been five decades since the isolation of nucleotide reductase activity in
      extracts of E. coli, this prototypical RNR continues to surprise us after all
      these years.

PMID- 22616863
TI  - Photoactivated structural dynamics of fluorescent proteins.
AB  - Proteins of the GFP (green fluorescent protein) family have revolutionized life
      sciences because they allow the tagging of biological samples in a non-invasive
      genetically encoded way. 'Phototransformable' fluorescent proteins, in
      particular, have recently attracted widespread interest, as their fluorescence
      state can be finely tuned by actinic light, a property central to the development
      of super-resolution microscopy. Beyond microscopy applications,
      phototransformable fluorescent proteins are also exquisite tools to investigate
      fundamental protein dynamics. Using light to trigger processes such as
      photoactivation, photoconversion, photoswitching, blinking and photobleaching
      allows the exploration of the conformational landscape in multiple directions. In
      the present paper, we review how structural dynamics of phototransformable
      fluorescent proteins can be monitored by combining X-ray crystallography, in
      crystallo optical spectroscopy and simulation tools such as quantum
      chemistry/molecular mechanics hybrid approaches. Besides their usefulness to
      rationally engineer better performing fluorescent proteins for nanoscopy and
      other biotechnological applications, these investigations provide fundamental
      insights into protein dynamics.

PMID- 22616864
TI  - The role of UBL domains in ubiquitin-specific proteases.
AB  - Ubiquitin conjugation and deconjugation provides a powerful signalling system to
      change the fate of its target enzymes. Ubiquitination levels are organized
      through a balance between ubiquitinating E1, E2 and E3 enzymes and
      deubiquitination by DUBs (deubiquitinating enzymes). These enzymes are tightly
      regulated to control their activity. In the present article, we discuss the
      different ways in which DUBs of the USP (ubiquitin-specific protease) family are
      regulated by internal domains with a UBL (ubiquitin-like) fold. The UBL domain in
      USP14 is important for its localization at the proteasome, which enhances
      catalysis. In contrast, a UBL domain in USP4 binds to the catalytic domain and
      competes with ubiquitin binding. In this process, the UBL domain mimics ubiquitin
      and partially inhibits catalysis. In USP7, there are five consecutive UBL
      domains, of which the last two affect catalytic activity. Surprisingly, they do
      not act like ubiquitin and activate catalysis rather than inhibiting it. These C
      terminal UBL domains promote a conformational change that allows ubiquitin
      binding and organizes the catalytic centre. Thus it seems that UBL domains have
      different functions in different USPs. Other proteins can modulate the roles of
      UBL domains in USP4 and USP7. On one hand, the inhibition of USP4 can be relieved
      when the UBL is sequestered by another USP. On the other, the activation of USP7
      is increased, when the UBL-activated state is stabilized by allosteric binding of
      GMP synthetase. Altogether, UBL domains appear to be able to regulate catalytic
      activity in USPs, but they can use widely different mechanisms of action, in
      which they may, as in USP4, or may not, as in USP7, use the direct resemblance to
      ubiquitin.

PMID- 22616865
TI  - Structural, mechanistic and regulatory studies of serine palmitoyltransferase.
AB  - SLs (sphingolipids) are composed of fatty acids and a polar head group derived
      from L-serine. SLs are essential components of all eukaryotic and many
      prokaryotic membranes but S1P (sphingosine 1-phosphate) is also a potent
      signalling molecule. Recent efforts have sought to inventory the large and
      chemically complex family of SLs (LIPID MAPS Consortium). Detailed understanding
      of SL metabolism may lead to therapeutic agents specifically directed at SL
      targets. We have studied the enzymes involved in SL biosynthesis; later stages
      are species-specific, but all core SLs are synthesized from the condensation of L
      serine and a fatty acid thioester such as palmitoyl-CoA that is catalysed by SPT
      (serine palmitoyltransferase). SPT is a PLP (pyridoxal 5'-phosphate)-dependent
      enzyme that forms 3-KDS (3-ketodihydrosphingosine) through a decarboxylative
      Claisen-like condensation reaction. Eukaryotic SPTs are membrane-bound multi
      subunit enzymes, whereas bacterial enzymes are cytoplasmic homodimers. We use
      bacterial SPTs (e.g. from Sphingomonas) to probe their structure and mechanism.
      Mutations in human SPT cause a neuropathy [HSAN1 (hereditary sensory and
      autonomic neuropathy type 1)], a rare SL metabolic disease. How these mutations
      perturb SPT activity is subtle and bacterial SPT mimics of HSAN1 mutants affect
      the enzyme activity and structure of the SPT dimer. We have also explored SPT
      inhibition using various inhibitors (e.g. cycloserine). A number of new subunits
      and regulatory proteins that have a direct impact on the activity of eukaryotic
      SPTs have recently been discovered. Knowledge gained from bacterial SPTs sheds
      some light on the more complex mammalian systems. In the present paper, we review
      historical aspects of the area and highlight recent key developments.

PMID- 22616866
TI  - Thiamin biosynthesis: still yielding fascinating biological chemistry.
AB  - The present paper describes the biosynthesis of the thiamin thiazole in Bacillus
      subtilis and Saccharomyces cerevisiae. The two pathways are quite different: in
      B. subtilis, the thiazole is formed by an oxidative condensation of glycine,
      deoxy-D-xylulose 5-phosphate and a protein thiocarboxylate, whereas, in S.
      cerevisiae, the thiazole is assembled from glycine, NAD and Cys205 of the
      thiazole synthase.

PMID- 22616867
TI  - Engineering oxidoreductases: maquette proteins designed from scratch.
AB  - The study of natural enzymes is complicated by the fact that only the most recent
      evolutionary progression can be observed. In particular, natural oxidoreductases
      stand out as profoundly complex proteins in which the molecular roots of
      function, structure and biological integration are collectively intertwined and
      individually obscured. In the present paper, we describe our experimental
      approach that removes many of these often bewildering complexities to identify in
      simple terms the necessary and sufficient requirements for oxidoreductase
      function. Ours is a synthetic biology approach that focuses on from-scratch
      construction of protein maquettes designed principally to promote or suppress
      biologically relevant oxidations and reductions. The approach avoids mimicry and
      divorces the commonly made and almost certainly false ascription of atomistically
      detailed functionally unique roles to a particular protein primary sequence, to
      gain a new freedom to explore protein-based enzyme function. Maquette design and
      construction methods make use of iterative steps, retraceable when necessary, to
      successfully develop a protein family of sturdy and versatile single-chain three-
      and four-alpha-helical structural platforms readily expressible in bacteria.
      Internally, they prove malleable enough to incorporate in prescribed positions
      most natural redox cofactors and many more simplified synthetic analogues.
      External polarity, charge-patterning and chemical linkers direct maquettes to
      functional assembly in membranes, on nanostructured titania, and to organize on
      selected planar surfaces and materials. These protein maquettes engage in light
      harvesting and energy transfer, in photochemical charge separation and electron
      transfer, in stable dioxygen binding and in simple oxidative chemistry that is
      the basis of multi-electron oxidative and reductive catalysis.

PMID- 22616868
TI  - Allosteric regulation of the biotin-dependent enzyme pyruvate carboxylase by
      acetyl-CoA.
AB  - The activity of the biotin-dependent enzyme pyruvate carboxylase from many
      organisms is highly regulated by the allosteric activator acetyl-CoA. A number of
      X-ray crystallographic structures of the native pyruvate carboxylase tetramer are
      now available for the enzyme from Rhizobium etli and Staphylococcus aureus.
      Although all of these structures show that intersubunit catalysis occurs, in the
      case of the R. etli enzyme, only two of the four subunits have the allosteric
      activator bound to them and are optimally configured for catalysis of the overall
      reaction. However, it is apparent that acetyl-CoA binding does not induce the
      observed asymmetrical tetramer conformation and it is likely that, under normal
      reaction conditions, all of the subunits have acetyl-CoA bound to them. Thus the
      activation of the enzyme by acetyl-CoA involves more subtle structural effects,
      one of which may be to facilitate the correct positioning of Arg353 and biotin in
      the biotin carboxylase domain active site, thereby promoting biotin carboxylation
      and, at the same time, preventing abortive decarboxylation of carboxybiotin. It
      is also apparent from the crystal structures that there are allosteric
      interactions induced by acetyl-CoA binding in the pair of subunits not optimally
      configured for catalysis of the overall reaction.

PMID- 22616869
TI  - Mycobacterium tuberculosis cytochrome P450 enzymes: a cohort of novel TB drug
      targets.
AB  - TB (tuberculosis) disease remains responsible for the death of over 1.5 million
      people each year. The alarming emergence of drug-resistant TB has sparked a
      critical need for new front-line TB drugs with a novel mode of action. In the
      present paper, we review recent genomic and biochemical evidence implicating
      Mycobacterium tuberculosis CYP (cytochrome P450) enzymes as exciting potential
      targets for new classes of anti-tuberculars. We also discuss HTS (high-throughput
      screening) and fragment-based drug-discovery campaigns that are being used to
      probe their potential druggability.

PMID- 22616870
TI  - The anaerobic biosynthesis of vitamin B12.
AB  - Vitamin B12 (cobalamin) is a cobalt-containing modified tetrapyrrole that is an
      essential nutrient for higher animals. Its biosynthesis is restricted to certain
      bacteria and requires approximately 30 enzymatic steps for its complete de novo
      construction. Remarkably, two distinct biosynthetic pathways exist, which are
      termed the aerobic and anaerobic routes. The anaerobic pathway has yet to be
      fully characterized due to the inherent instability of its oxygen-sensitive
      intermediates. Bacillus megaterium, a bacterium previously used for the
      commercial production of cobalamin, has a complete anaerobic pathway and this
      organism is now being used to investigate the anaerobic B12 pathway through the
      application of recent advances in recombinant protein production. The present
      paper provides a summary of recent findings in the anaerobic pathway and future
      perspectives.

PMID- 22616871
TI  - Cholesterol, an essential molecule: diverse roles involving cytochrome P450
      enzymes.
AB  - Cholesterol is an essential molecule for eukaryotic life and is an important
      precursor for a wide range of physiological processes. Biosynthesis and
      homoeostasis of cholesterol are complex mechanisms that are tightly regulated and
      interlinked with activities of a number of cytochrome P450 enzymes. These P450s
      play central critical roles in cholesterol metabolism. Key roles include a rate
      limiting reaction in the synthesis of cholesterol itself, and in the oxidative
      transformations of cholesterol into steroid hormones and bile acids. However,
      microbial P450s also have important roles that impinge directly on human
      cholesterol synthesis and oxidation. Recent data reveal that Mycobacterium
      tuberculosis (which infects more than one-third of the world's human population)
      uses P450s to initiate breakdown of host cholesterol as an energy source.
      Microbial P450s also catalyse industrially important transformations in the
      synthesis of cholesterol-lowering statin drugs, with clear benefits to humans.
      The present article reviews the various roles of P450s in human cholesterol
      metabolism, from endogenous P450s through to microbial oxidases that enable
      catabolism of human cholesterol, or facilitate production of statins that
      regulate cholesterol production with positive outcomes in cardiovascular disease.

PMID- 22616873
TI  - First reported use of the heartware HVAD in the US as bridge to transplant in an
      adolescent.
AB  - Limited options exist for mechanical circulatory support as a bridge to
      transplantation in pediatric patients with advanced heart failure. This is
      particularly true when it comes to intracorporeal technologies. We describe the
      first reported experience with the use of the HVAD in the US as a successful
      bridge to transplantation in a 13-yr-old patient.

PMID- 22616874
TI  - Association between insight, cognitive insight, positive symptoms and violence in
      patients with schizophrenia.
AB  - BACKGROUND: Violence is a significant clinical and public concern and is a
      frequent occurrence in patients with schizophrenia. The relationship between
      insight and violence remains controversial. In addition, there is a lack of
      research on insight, cognitive insight, demographic and psychopathologic
      variables in violent versus nonviolent schizophrenia patients. AIM: We aimed to
      compare insight, cognitive insight, psychopathological and demographic variables
      in violent and nonviolent subjects suffering from schizophrenia. In addition, we
      aimed to determine the demographic and clinical predictors of violent behaviour
      in patients with schizophrenia. METHOD: We recruited 133 schizophrenic patients
      without concomitant substance abuse or axis II disorder. Diagnoses were based on
      the SCID-I and SCID-II. Violent behaviours were assessed using the Overt
      Aggression Scale. Insight and cognitive insight were assessed with the Scale to
      Assess Unawareness of Mental Disorder and the Beck Cognitive Insight Scale,
      respectively. RESULTS: We compared 47 patients with violent schizophrenia with 86
      nonviolent patients. Non-violent patients had more severe depression, lower
      scores on positive symptoms, better clinical insight, more self-reflectivity and
      higher R-C index scores than did violent patients. In addition, history of
      violence, lower self-reflectiveness, worse clinical insight and delusion severity
      were significant predictors of violence in schizophrenia. CONCLUSION: The present
      study suggests that the inclusion of insight and cognitive insight may increase
      the prediction of violence in this population. In addition, clinicians should
      consider using non-pharmacological techniques that are based on cognitive
      behaviour therapy and enhance insight, particularly cognitive insight, among
      patients with schizophrenia who exhibit violent behaviour.

PMID- 22616875
TI  - Homotopy semi-numerical simulation of peristaltic flow of generalised Oldroyd-B
      fluids with slip effects.
AB  - This investigation deals with the peristaltic flow of generalised Oldroyd-B
      fluids (with the fractional model) through a cylindrical tube under the influence
      of wall slip conditions. The analysis is carried out under the assumptions of
      long wavelength and low Reynolds number. Analytical approximate solutions are
      obtained by using the highly versatile and rigorous semi-numerical procedure
      known as the homotopy analysis method. It is assumed that the cross section of
      the tube varies sinusoidally along the length of the tube. The effects of the
      dominant hydromechanical parameters, i.e. fractional parameters, material
      constants, slip parameter, time and amplitude on the pressure difference across
      one wavelength, are studied. Graphical plots reveal that the influence of both
      fractional parameters on pressure is opposite to each other. Interesting
      responses to a variation in the constants are obtained. Pressure is shown to be
      reduced by increasing the slip parameter. Furthermore, the pressure in the case
      of fractional models (fractional Oldroyd-B model and fractional Maxwell model) of
      viscoelastic fluids is considerably more substantial than that in the
      corresponding classical viscoelastic models (Oldroyd-B and Maxwell models).
      Applications of the study arise in biophysical food processing, embryology and
      gastro-fluid dynamics.

PMID- 22616876
TI  - Hierarchically structured multifunctional porous interfaces through water
      templated self-assembly of ternary systems.
AB  - Herein, a facile water-assisted templating approach, the so-called breath figures
      method, has been employed to prepare multifunctional and hierarchically
      structured porous patterned films with order at different length scales (nano-
      and micrometer). Tetrahydrofuran solutions of ternary blends consisting on high
      molecular weight polystyrene, an amphiphilic block copolymer, polystyrene-b
      poly[poly(ethylene glycol) methyl ether methacrylate] (PS(40)-b-P(PEGMA300)(48)),
      and a fluorinated copolymer, polystyrene-b-poly(2,3,4,5,6-pentafluorostyrene)
      (P5FS(21)-b-PS(31)), have been used to obtain films varying the proportion of the
      three components. Confocal micro-Raman spectroscopy and atomic force microscopy
      demonstrated the preferential location of the different functionalities in the
      films. Because of the breath figures mechanism, the amphiphilic copolymer yield
      pores enriched in hydrophilic functionality while the fluorinated copolymer
      remained mixed with the PS matrix and eventually also forming self-assembled
      nanostructures at the surface. As a consequence, two levels of order can be
      observed, i.e., micrometer size pores with nanostructured domains due to the
      block copolymer self-assembly. In addition, the distribution of the amphiphilic
      copolymer within the holes is not regular being located principally on the edges
      of the cavities. This can be attributed to the coffee stain phenomenon occurring
      in the water droplets as a consequence of the segregation of the block copolymers
      to the droplets and their self-assembly.

PMID- 22616877
TI  - Photophysics and dynamics of surface plasmon polaritons-mediated energy transfer
      in the presence of an applied electric field.
AB  - The possibility to transfer energy between molecular excitons across a metal film
      up to 150 nm thick represents a very attractive solution to control and improve
      the performances of thin optoeletronic devices. This process involves the
      presence of coupled surface plasmon polaritons (SPPs) at the two dielectric-metal
      interfaces, capable of mediating the interactions between donor and acceptor,
      located on opposite sides of the metal film. In this Article, the photophysics
      and the dynamics of an efficient SPP-mediated energy transfer between a suitable
      dye and a conjugated polymer is characterized by means of steady-state and time
      resolved photoluminescence techniques. The process is studied in model multilayer
      structures (donor/metal/acceptor) as well as in electrically pumped
      heterostructures (donor/metal cathode/acceptor/anode), to verify the effects of
      applied electric fields on the efficiency and the dynamics of SPP-mediated energy
      transfer. A striking enhancement of the overall luminescence was recorded in a
      particular range of applied bias, suggesting the presence of cooperative effects
      between optical and electrical stimulations.

PMID- 22616878
TI  - The development of children's ability to fill the gaps in their knowledge by
      consulting experts.
AB  - This research investigated children's ability to recognize gaps in their
      knowledge and seek missing information from appropriate informants. In Experiment
      1, forty-five 4- and 5-year-olds were adept in assigning questions from 3 domains
      (medicine, firefighting, and farming) to corresponding experts (doctor,
      firefighter, or farmer). However, when given the options of answering the same
      questions themselves or assigning them to an expert (Experiment 2), only 6-year
      olds were consistently able to recognize when they did not know answers and then
      assign test questions correctly. Four- and 5-year-olds tended to overestimate
      their own knowledge or assign questions to the wrong expert. This result was
      replicated in Experiment 3, in which 5-year-olds were given incentives for
      correct answers.

PMID- 22616879
TI  - Pharmacokinetics of florfenicol and its metabolite, florfenicol amine, in rice
      field eel (Monopterus albus) after a single-dose intramuscular or oral
      administration.
AB  - The pharmacokinetics of florfenicol (FF) and its metabolite, florfenicol amine
      (FFA), were studied in rice field eel (Monopterus albus) after a single dose (20
      mg/kg) by intramuscular (i.m.) or oral gavage (p.o.) dose at 25  degrees C. The
      elimination half-lives (t1/2beta ), peak concentration of FF (Cmax ), and time to
      reach FF peak concentration (Tmax ) in plasma were estimated as 18.39 h, 10.83
      MUg/mL, and 7.00 h, respectively, after i.m. injection and 13.46 h, 8.37 MUg/mL,
      and 5 h, respectively, after p.o. administration. The Tmax values of FF in
      tissues (i.e., kidney, muscle, and liver) were larger for i.m. injection compared
      with those for p.o. administration. The t1/2beta had the following order
      kidney>muscle>liver for i.m. administrated and kidney>liver>muscle for p.o.
      administrated. The largest area under the concentration-time curve (AUC) was
      calculated to be 384.29 mg.h/kg after i.m. dosing, and the mean residence time
      (MRT) was 42.46 h by oral administration in kidney. FFA was also found in all
      tissues with a lower concentration than FF for both i.m. and p.o. administrations
      throughout the study. The elimination of FFA was slow with a t1/2beta between
      18.19 and 47.80 h in plasma and tissues. The mean metabolic rate of FFA for i.m.
      and p.o. administrations was >23.30%.

PMID- 22616880
TI  - Diptera vectors of avian Haemosporidian parasites: untangling parasite life
      cycles and their taxonomy.
AB  - Haemosporida is a large group of vector-borne intracellular parasites that infect
      amphibians, reptiles, birds, and mammals. This group includes the different
      malaria parasites (Plasmodium spp.) that infect humans around the world. Our
      knowledge on the full life cycle of these parasites is most complete for those
      parasites that infect humans and, to some extent, birds. However, our current
      knowledge on haemosporidian life cycles is characterized by a paucity of
      information concerning the vector species responsible for their transmission
      among vertebrates. Moreover, our taxonomic and systematic knowledge of
      haemosporidians is far from complete, in particular because of insufficient
      sampling in wild vertebrates and in tropical regions. Detailed experimental
      studies to identify avian haemosporidian vectors are uncommon, with only a few
      published during the last 25 years. As such, little knowledge has accumulated on
      haemosporidian life cycles during the last three decades, hindering progress in
      ecology, evolution, and systematic studies of these avian parasites. Nonetheless,
      recently developed molecular tools have facilitated advances in haemosporidian
      research. DNA can now be extracted from vectors' blood meals and the vertebrate
      host identified; if the blood meal is infected by haemosporidians, the parasite's
      genetic lineage can also be identified. While this molecular tool should help to
      identify putative vector species, detailed experimental studies on vector
      competence are still needed. Furthermore, molecular tools have helped to refine
      our knowledge on Haemosporida taxonomy and systematics. Herein we review studies
      conducted on Diptera vectors transmitting avian haemosporidians from the late
      1800s to the present. We also review work on Haemosporida taxonomy and
      systematics since the first application of molecular techniques and provide
      recommendations and suggest future research directions. Because human
      encroachment on natural environments brings human populations into contact with
      novel parasite sources, we stress that the best way to avoid emergent and
      reemergent diseases is through a program encompassing ecological restoration,
      environmental education, and enhanced understanding of the value of ecosystem
      services.

PMID- 22616881
TI  - Light-harvesting fullerene dyads as organic triplet photosensitizers for triplet
      triplet annihilation upconversions.
AB  - Visible light-harvesting C(60)-bodipy dyads were devised as universal organic
      triplet photosensitizers for triplet-triplet annihilation (TTA) upconversion. The
      antennas in the dyad were used to harvest the excitation energy, and then the
      singlet excited state of C(60) will be populated via the intramolecular energy
      transfer from the antenna to C(60) unit. In turn with the intrinsic intersystem
      crossing (ISC) of the C(60), the triplet excited state of the C(60) will be
      produced. Thus, without any heavy atoms, the triplet excited states of organic
      dyads are populated upon photoexcitation. Different from C(60), the dyads show
      strong absorption of visible light at 515 nm (C-1, epsilon = 70400 M(-1) cm(-1))
      or 590 nm (C-2, epsilon = 82500 M(-1) cm(-1)). Efficient intramolecular energy
      transfer from the bodipy moieties to C(60) unit and localization of the triplet
      excited state on C(60) were confirmed by steady-state and time-resolved
      spectroscopy as well as DFT calculations. The dyads were used as triplet
      photosensitizers for TTA upconversion, and an upconversion quantum yield up to
      7.0% was observed. We propose that C(60)-organic chromophore dyads can be used as
      a general molecular structural motif for organic triplet photosensitizers, which
      can be used for photocatalysis, photodynamic therapy, and TTA upconversions.

PMID- 22616882
TI  - MicroRNA-34a and microRNA-21 play roles in the chemopreventive effects of 3,6
      dihydroxyflavone on 1-methyl-1-nitrosourea-induced breast carcinogenesis.
AB  - INTRODUCTION: miRNAs are very important regulators in biological processes such
      as development, cellular differentiation, and carcinogenesis. Given the important
      role of miRNAs in tumorigenesis and development, it is worth investigating
      whether some miRNAs play roles in the anticancer mechanism of flavonoids.
      However, such a role has not yet been reported. We previously selected the
      promising anticancer agent 3,6-dihydroxyflavone (3,6-DHF) in pharmacodynamic
      experiments, which may serve as a leading compound for developing more potent
      anticancer drugs or chemopreventive supplements. The present study aims to
      investigate the chemopreventive activities of 3,6-DHF against mammary
      carcinogenesis. METHODS: The experimental model of breast carcinogenesis was
      developed by intraperitoneal injection of 1-methyl-1-nitrosourea (MNU). The
      bioavailability of 3,6-DHF in rats was detected by HPLC. The expression of
      microRNA-34a (miR-34a) and microRNA-21 (miR-21) was evaluated by real-time
      quantitative RT-PCR. Cell apoptosis was analyzed by flow cytometry or terminal
      deoxynucleotidyl transferase dUTP nick end-labeling assay. The mitochondrial
      membrane potential was assayed using 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl
      imidacarbocyanine iodide dye by confocal laser scanning microscopy. The level of
      cytochrome C in cytosol was evaluated by western blotting. RESULTS: Our study
      showed that oral administration of 3,6-DHF effectively suppressed MNU-induced
      breast carcinogenesis in rats, decreasing the cancer incidence by 35.7%. The
      detection of bioavailability indicated that the concentration of 3,6-DHF was 2.5
      +/- 0.4 MUg/ml in plasma of rats within 2 hours after administration, and was
      21.7 +/- 3.8 MUg/ml in urine within 24 hours. Oral administration of 3,6-DHF to
      BALB/c nude mice bearing breast cancer cell xenografts also significantly
      suppressed tumor growth in vivo. Furthermore, our study revealed that the global
      upregulation of miR-21 and downregulation of miR-34a in breast carcinogenesis
      could be reversed by 3,6-DHF, which significantly upregulated miR-34a expression
      and decreased miR-21 expression - inducing apoptosis of breast cancer cells in
      vitro and in vivo. Overexpression of miR-34a induced by plasmid transfection or
      inhibition of miR-21 by oligonucleotides markedly promoted the pro-apoptotic
      effect of 3,6-DHF. Inactivation of miR-34a or overproduction of miR-21
      compromised the anticancer effects of 3,6-DHF. CONCLUSION: These findings
      indicate that 3,6-DHF is a potent natural chemopreventive agent, and that miR-34a
      and miR-21 play roles in MNU-induced breast carcinogenesis and the anticancer
      mechanism of flavonoids.

PMID- 22616884
TI  - Childhood injury prevention revisited.

PMID- 22616883
TI  - Ascorbic acid reduction of compound I of mammalian catalases proceeds via
      specific binding to the NADPH binding pocket.
AB  - Mammalian (Clade 3) catalases utilize NADPH as a protective cofactor to prevent
      one-electron reduction of the central reactive intermediate Compound I (Cpd I) to
      the catalytically inactive Compound II (Cpd II) species by re-reduction of Cpd I
      to the enzyme's resting state (ferricatalase). It has long been known that
      ascorbate/ascorbic acid is capable of reducing Cpd I of NADPH-binding catalases
      to Cpd II, but the mode of this one-electron reduction had hitherto not been
      explored. We here demonstrate that ascorbate-mediated reduction of Cpd I,
      generated by addition of peroxoacetic acid to NADPH-free bovine liver catalase
      (BLC), requires specific binding of the ascorbate anion to the NADPH binding
      pocket. Ascorbate-mediated Cpd II formation was found to be suppressed by added
      NADPH in a concentration-dependent manner, for the achievement of complete
      suppression at a stoichiometric 1:1 NADPH:heme concentration ratio. Cpd I -> Cpd
      II reduction by ascorbate was similarly inhibited by addition of NADH, NADP(+),
      thio-NADP(+), or NAD(+), though with 0.5-, 0.1-, 0.1-, and 0.01-fold reduced
      efficiencies, respectively, in agreement with the relative binding affinities of
      these dinucleotides. Unexpected was the observation that although Cpd II
      formation is not observed in the presence of NADP(+), the decay of Cpd I is
      slightly accelerated by ascorbate rather than retarded, leading to direct
      regeneration of ferricatalase. The experimental findings are supported by
      molecular mechanics docking computations, which show a similar binding of NADPH,
      NADP(+), and NADH, but not NAD(+), as found in the X-ray structure of NADPH
      loaded human erythrocyte catalase. The computations suggest that two ascorbate
      molecules may occupy the empty NADPH pocket, preferably binding to the adenine
      binding site. The biological relevance of these findings is discussed.

PMID- 22616885
TI  - Agree to disagree.

PMID- 22616886
TI  - Tattoos, piercing, and sexual behaviors in young adults.
AB  - INTRODUCTION: Body piercing and tattooing are accepted by a growing number of
      teenagers and young adults as a way of self-expressing. Some authors suggest
      association between body piercings/tattoos and early sexual initiation, higher
      number of sexual partners, or risky sexual behaviors. AIM: The aim of the study
      was to evaluate sexual behaviors among young adults with body modifications (BMs)
      -tattoos and piercings. METHODS: One hundred twenty young healthy adults, ages
      between 20 and 35, were included in the population study. The study group was
      divided into three subgroups: controls (N = 60), adults with tattoos (N = 28),
      and adults with piercings (N = 32). The research instrument was a self-prepared
      questionnaire containing 59 questions assessing socioepidemiological parameters,
      sexual behaviors, incidents of sexual harassment in the past, and self
      attractiveness evaluation, as well as questions concerning tattoos and piercings.
      Socioepidemiological variables and sexual behaviors were compared between
      subgroups. MAIN OUTCOME MEASURES: To assess and describe the correlation between
      having BM--tattoos and piercing--and sexual behaviors in the population of young
      adults by using the logistic regression model. RESULTS: Adults with BMs have had
      their first intercourse statistically earlier and were more sexually active
      compared with controls. There were no statically significant differences in
      sexual orientation, sexual preferences, engaging in risky sexual behaviors,
      frequency of masturbation, and history of sexual abuse between the groups. In
      contrast, the frequency of sexual intercourses was statistically higher and oral
      sex was more likely to be a dominant sexual activity in adults with BM compared
      with controls. The multivariate logistic model revealed that adults with BM were
      four times less likely to participate in religious practices and twice more
      likely to have early sexual initiation. CONCLUSIONS: Having BM is associated with
      early sexual initiation and more liberal attitudes toward sexual behaviors but
      not with engaging in risky sexual behaviors.

PMID- 22616887
TI  - Late graft failure in FA--case report and review of the literature.
AB  - Hematological disorders in patients with FA can only be cured by allogeneic HSCT.
      Severe infections in primary and early secondary graft failures pose a particular
      risk. Whereas most graft failures occur within 100 days, those observed after day
      +100 are infrequent. Here, we present our analysis of a secondary graft failure
      more than five yr after a first allogeneic HSCT. In this patient, isolated
      thrombocytopenia over a period of 12 months resulted in a chimerism subset
      analysis revealing a considerable decrease in the CD34-positive donor cell
      fraction. After a second fludarabine-based preparative regimen, the patient
      received PBSC from the same donor. Chimerism returned to full donor in all
      subsets. This clinical course demonstrates that isolated thrombocytopenia can
      precede complete graft failure for several months. Our review of the literature
      on late graft failures in patients with FA after day +100 reveals the absence of
      fludarabine in the preparative regimen as a potential risk factor. Further
      clinical research is necessary to identify more suitable approaches for ensuring
      safe and stable engraftment.

PMID- 22616888
TI  - Silver triflate and palladium acetate co-catalyzed reaction of N'-(2
      alkynylbenzylidene)hydrazide with N-allyl ynamide.
AB  - A silver triflate and palladium acetate co-catalyzed reaction of N'-(2
      alkynylbenzylidene)hydrazide with N-allyl ynamide is described, which generates 2
      amino-H-pyrazolo[5,1-a]isoquinolines in good to excellent yield. The
      transformation proceeds with high efficiency through 6-endo cyclization, [3 + 2]
      cycloaddition, 3,3-sigmatropic rearrangement, and aromatization.

PMID- 22616890
TI  - Respiratory assessment and management in bariatric surgery.
AB  - The prevalence of obesity and overweight is growing in adults and children
      worldwide. With the failure of diets and lifestyle factors, more people are
      looking to bariatric surgery to address this significant medical problem. Severe
      obesity may be associated with significant perioperative respiratory
      complications. This article reviews potential respiratory and sleep
      complications, screening, and management of these problems.

PMID- 22616889
TI  - Cerebral hemodynamics and baroreflex sensitivity after carotid artery stenting.
AB  - OBJECTIVES: The long-term hemodynamic effects of carotid angioplasty and stenting
      (CAS) are unclear. We performed a longitudinal study to investigate the
      variations in cerebral hemodynamics in patients undergoing CAS. MATERIALS AND
      METHODS: We performed prospective evaluation of 63 symptomatic male patients (19
      patients had transient ischemic attack and 44 had minor stroke; mean age: 77.3 +/
      6.3 years [range: 51-86]). The mean blood flow velocities (MBFV) and pulsatility
      index (PI) of the middle cerebral arteries (MCA) on both sides were evaluated
      using transcranial color-coded Doppler (TCCD) ultrasonography. Cardiac autonomic
      activities were evaluated by measuring baroreflex sensitivity (BRS). All
      parameters were measured at baseline prior to CAS and at 1, 3, 6, and 12 months
      after CAS. RESULTS: The preoperative MBFV and PI of the ipsilateral MCA were
      significantly lower than those of the contralateral side. However, after CAS,
      MBFV in the ipsilateral MCA increased significantly until 2 weeks after stenting,
      after which the MBFV gradually decreased and remained stable for 1 year after
      CAS. Further, we observed a nonsignificant increase in MBFV in the contralateral
      MCA after CAS. In contrast to the MBFV, the BRS values decreased significantly 1
      month after stenting and returned to baseline levels 6 months after CAS.
      CONCLUSIONS: Patients with CAS showed improved global cerebral hemodynamic
      status. However, the BRS did not normalize initially, and baseline value was
      achieved at 6 months after stenting.

PMID- 22616891
TI  - Associations of cardiovascular risk factors with prehypertension and hypertension
      in women.
AB  - The purpose of this study was to clarify the relationships of cardiovascular risk
      factors with prehypertension and hypertension in women. Japanese women (35-54
      years old, n = 9939) were divided by blood pressure into normotensive,
      prehypertensive and hypertensive groups. Odds ratios (ORs) for prehypertension
      and hypertension were calculated after adjustment for confounding factors such as
      age, smoking, alcohol intake, habitual exercise, body mass index (BMI), and/or
      therapy for dyslipidemia or diabetes. ORs of light drinkers and heavy drinkers vs
      non-drinkers for prehypertension and hypertension were significantly higher than
      a reference level of 1.00, whereas ORs for prehypertension and hypertension of
      smokers vs non-smokers were significantly lower than the reference level. ORs of
      the obese group (high BMI or waist-to-height ratio) vs the non-obese group for
      prehypertension and hypertension were significantly higher than the reference
      level. ORs for prehypertension and hypertension of the subject group with vs
      without high triglycerides or low-density lipoprotein (LDL)-cholesterol were
      significantly higher than the reference level. Thus, obesity, alcohol drinking
      and dyslipidemias such as high triglycerides and high LDL-cholesterol are
      associated with prehypertension and hypertension in women. Interventional studies
      on whether correction of obesity and dyslipidemias and restriction of alcohol
      consumption are beneficial for prevention of prehypertension and hypertension in
      women need to be carried out.

PMID- 22616892
TI  - Acid-labile traceless click linker for protein transduction.
AB  - Intracellular delivery of active proteins presents an interesting approach in
      research and therapy. We created a protein transduction shuttle based on a new
      traceless click linker that combines the advantages of click reactions with 
      implementation of reversible pH-sensitive bonds. The azidomethyl-methylmaleic
      anhydride (AzMMMan) linker was found compatible with different click chemistries,
      demonstrated in bioreversible protein modification with dyes, polyethylene
      glycol, or a transduction carrier. Linkages were stable at physiological pH but
      reversible at the mild acidic pH of endosomes or lysosomes. We show that pH
      reversible attachment of a defined endosome-destabilizing three-arm oligo(ethane
      amino)amide carrier generates an effective shuttle for protein delivery. The
      cargo protein nlsEGFP, when coupled via the traceless AzMMMan linker, experiences
      efficient cellular uptake and endosomal escape into the cytosol, followed by
      import into the nucleus. In contrast, irreversible linkage to the same shuttle
      hampers nuclear delivery of nlsEGFP which after uptake remains trapped in the
      cytosol. Successful intracellular delivery of bioactive beta-galactosidase as a
      model enzyme was also demonstrated using the pH-controlled shuttle system.

PMID- 22616893
TI  - Comment on "Source-like solution for radial imbibition into a homogeneous semi
      infinite porous medium".

PMID- 22616894
TI  - Confocal imaging of trans-epithelial trafficking by immune and umbilical cord
      stem cells in the neonatal porcine intestine.
AB  - Maternal colostral leucocytes (CL) and peripheral blood mononuclear cells (PBMC)
      enter the neonatal circulation after ingestion in pigs and cattle. Porcine
      umbilical cord matrix stem cells (PUCs) are relatively non-immunogenic after
      initial allogeneic transplantation. Using intestinal explant cultures incubated
      with labelled cells and confocal microscopy, we demonstrated trans-epithelial
      trafficking of exogenous CL, PBMC and PUCs below the luminal surface after 72 h
      of culture. We orally administered PBMC and PUCs to pre-colostral neonatal pigs
      and tracked their location 8 or 24 h later. Both PBMC and PUCs were found in the
      intestinal wall of all samples. Exposure to 25% of acellular colostrum had no
      detected effect on trafficking. Labelled PUCs and PBMC were detected on the
      surface of the epithelium and in the lamina propria 8 h post-treatment and PBMC
      were also in the superficial submucosa. At 24 h, PUCs and PBMC were observed on
      the surface of the epithelium, in the lamina propria, superficial submucosa and
      deep submucosa. Our findings show the potential of PUCs for allogeneic
      engraftment in the neonatal intestine and may lead to cell-based delivery of
      therapeutics.

PMID- 22616895
TI  - Intercultural communication in health care: challenges and solutions in work
      rehabilitation practices and training: a comprehensive review.
AB  - PURPOSE: The purpose of this comprehensive literature review it to explore cross
      cultural issues in occupational rehabilitation and work disability prevention.
      METHOD: A literature review on cross-cultural issues was performed in medicine,
      health sciences, and social sciences databases (PubMed, Ingenta, Canadian Centre
      for Occupational Health and Safety, Ergonomics Abstract, Google Scholar, OSH
      Update and the Quebec Workers' Compensation Board data base). A total of 27
      documents published until 2010 in English or French were selected and analyzed.
      RESULTS: Cross-cultural issues in occupational rehabilitation show that
      representations of pain, communication and therapist-patient relationship and
      intercultural competence could be presented as the major topics covered in the
      selected literature. As for the general topic of immigrant workers and OSH,
      barriers were identified revealing personal, relational, contextual and
      structural levels that put immigrant and minority workers in situation of
      vulnerability (ex. linguistic and cultural barriers, lack of knowledge of the
      system, precarious work or exposition to higher risk hazards, etc.). Cultural
      issues in occupational rehabilitation put less attention to work-related
      contextual factors but emphasized on attitude and pain behaviours, perceptions of
      illness and appropriate treatment, therapist-patient relationship and cultural
      competences among OT professionals. CONCLUSIONS: The growth of immigration in
      countries such as Canada poses a real challenge to the delivery of health care
      and rehabilitation services. Despite growing concerns in providing culturally
      appropriate heath cares, intervention models, tools and training tools are still
      lacking in occupational rehabilitation and disability management. Nevertheless,
      cultural competence seems to be a promising concept to be implemented in work
      rehabilitation and disability management.

PMID- 22616896
TI  - Assessment of flavonoids contents and in vitro antioxidant activity of Launaea
      procumbens.
AB  - BACKGROUND: Launaea procumbens (LP) has been used as a food supplement in
      Pakistan. In this study methanolic crude extract (LPME) of the whole plant and
      its different fractions; n-hexane (LPHE); ethyl acetate (LPEE) and chloroform
      (LPCE) were studied for the determination of total flavonoid and phenolics
      contents along with multifaceted in vitro scavenging assays. RESULTS:
      Considerable amount of flavonoid and phenolics contents were found in all the
      fractions. Methanol and chloroform fraction exhibited efficient scavenging of
      DPPH., ABTS.+, .OH, superoxide, lipid peroxide and nitric oxide free radicals.
      Significant correlation was found between DPPH., ABTS.+, superoxide radical, beta
      carotene bleaching restraint and phosphomolybdenum assay with total flavonoids
      and phenolics contents. High performance chromatography (HPLC) of LPME revealed
      the presence of vitexin, orientin, rutin, hyperoside, catechin and myricetin.
      CONCLUSION: These results reveal the presence of bioactive compounds in LPME,
      which might be contributed towards the various in vitro scavenging.

PMID- 22616897
TI  - Importance of diameter-to-length ratio in selecting dental implants: a
      methodological finite element study.
AB  - Implant dimensions greatly influence load transfer characteristics and the
      lifetime of a dental system. Excessive stresses at peri-implant area may result
      in bone failure. Finding the critical point at the implant-bone interface and
      evaluating the influence of implant diameter-to-length ratio on adjacent bone
      stresses makes it possible to select implant dimensions. For this, different
      cylindrical implants were numerically analysed using geometrical models generated
      from computed tomography images of mandible with osseointegrated implants. All
      materials were assumed to be linearly elastic and isotropic. Masticatory load was
      applied in its natural direction, oblique to occlusal plane. Maximum von Mises
      stresses were located around the implant neck at the critical point of its
      intersection with the plane of loading and were functions of implant diameter-to
      length ratio. It was demonstrated that there exists a certain spectrum of
      diameter-to-length ratios, which will keep maximum bone stresses at a preset
      level chosen in accordance with patient's bone strength.

PMID- 22616898
TI  - Counting the nouns: simple structural cues to verb meaning.
AB  - Two-year-olds use the sentence structures verbs appear in--subcategorization
      frames--to guide verb learning. This is syntactic bootstrapping. This study
      probed the developmental origins of this ability. The structure-mapping account
      proposes that children begin with a bias toward one-to-one mapping between nouns
      in sentences and participant roles in events. This account predicts that
      subcategorization frames should guide very early verb learning, if the number of
      nouns in the sentences is informative. In 3 experiments, one hundred and thirty
      six 21- and 19-month-olds assigned appropriately different interpretations to
      novel verbs in transitive ("He's gorping him!") versus intransitive sentences
      ("He's gorping!") differing in their number of nouns. Thus, subcategorization
      frames guide verb interpretation in very young children. These findings constrain
      theoretical proposals about mechanisms for syntactic bootstrapping.

PMID- 22616900
TI  - Risk factor burden predicts long-term mortality in young patients with arterial
      cerebral infarction.
AB  - OBJECTIVE: The aim was to investigate risk factors separately and in sum in
      relation to long-term mortality after arterial cerebral infarction in young
      adults. MATERIALS AND METHODS: Mortality in relation to the number of risk
      factors (smoking, hypertension, hypercholesterolemia, diabetes mellitus,
      myocardial infarction, angina pectoris, and intermittent claudication known at
      the time of the index stroke) and etiology was studied in a population of young
      adults with first-ever arterial ischemic stroke at an age < 50 years. Cox
      regression analyses were performed. RESULTS: After a mean follow-up time of 18
      years (the longest follow-up study after cerebral infarction in young adults),
      12.5% with no risk factor had died while the corresponding frequencies in
      patients with 1-3 or more risk factors were 18.5%, 25.4%, and 53.1%, respectively
      (P < 0.001). The number of risk factors was associated with mortality on Cox
      regression analysis [hazard ratio (HR) = 1.6, P = 0.001]. A separate Cox
      regression analysis showed mortality to be associated with diabetes mellitus (HR
      = 3.0, P = 0.001), myocardial infarction (HR = 3.1, P = 0.001), and alcoholism
      (HR = 6.3, P < 0.001). CONCLUSION: Increasing number of traditional risk factors
      is associated with long-term mortality in young adults with cerebral infarction
      indicating aggressive long-term secondary preventive treatment in selected
      patients.

PMID- 22616899
TI  - Influence of ethnicity and socioeconomic factors on outcome after total hip
      replacement.
AB  - BACKGROUND: Previous studies have documented ethnic differences in the
      utilization of total hip arthroplasty. Less is known if this operation is
      performed at the same stage of symptoms and has equal effects in patients with
      different ethnicity. AIM: We investigated whether patients born outside Sweden
      report equal effects of operation with the insertion of a total hip replacement
      in terms of EQ-5D, pain and overall satisfaction as those born in Sweden. METHOD:
      Preoperative and 1-year postoperative data from Swedish Hip Arthroplasty
      Register, (1216 patients,1216 hips) with primary osteoarthritis of the hip
      operated between years 2002 and 2006, were analysed. All patients completed the
      EQ-5D form, filled in a VAS about pain preoperatively and at 1 year
      postoperatively, when a VAS about overall satisfaction was added. FINDINGS:
      Before the operation and after adjustment for confounders, patients born abroad
      reported more problems (dichotomized into no or moderate/severe problems), with
      self-care (p = 0.01) and anxiety/depression (p = 0.02) in the EQ-5D form than
      those born in Sweden. They also had more pain (VAS, p = 0.04). One year after the
      operation and after statistical adjustments, patients born outside Sweden
      reported lower scores for self-care (p = 0.008) and usual activities (p = 0.001)
      in the EQ-5D form. They still reported more pain (VAS, p = 0.02), but no
      significant difference concerning degree of satisfaction (p = 0.3). CONCLUSIONS:
      Our finding of more preoperative disability and pain (VAS) before the operation
      in patients born abroad might depend on cultural differences, communication
      problems and differences in indications. Even if the effect of the total hip
      replacement was good, patients born abroad scored less for some of the items at 1
      year. We think that this patient group could benefit from improved pre- and
      postoperative information and other measures to facilitate and improve their
      rehabilitation.

PMID- 22616901
TI  - Chemoselective Schmidt reaction mediated by triflic acid: selective synthesis of
      nitriles from aldehydes.
AB  - An excellent utility of Schmidt reaction of aldehydes to access corresponding
      nitriles in an instantaneous reaction is demonstrated. The reaction of aldehydes
      with NaN(3) and TfOH furnishes the corresponding nitriles in near quantitative
      yields and tolerates a variety of electron-withdrawing and electron-donating
      substituents on the substrates. Formanilides, a common side product in Schmidt
      reaction, is not observed in this reaction. Besides these advantages, the salient
      feature of this reaction is that it exhibits a remarkable chemoselectivity, as
      acid and ketone functionalities are well tolerated under the reaction conditions.
      The reaction is easily scalable, high yielding, and nearly instantaneous.

PMID- 22616902
TI  - Rational design of 4-aryl-1,2,3-triazoles for indoleamine 2,3-dioxygenase 1
      inhibition.
AB  - Indoleamine 2,3-dioxygenase 1 (IDO1) is an important therapeutic target for the
      treatment of diseases such as cancer that involve pathological immune escape.
      Starting from the scaffold of our previously discovered IDO1 inhibitor 4-phenyl
      1,2,3-triazole, we used computational structure-based methods to design more
      potent ligands. This approach yielded highly efficient low molecular weight
      inhibitors, the most active being of nanomolar potency both in an enzymatic and
      in a cellular assay, while showing no cellular toxicity and a high selectivity
      for IDO1 over tryptophan 2,3-dioxygenase (TDO). A quantitative structure-activity
      relationship based on the electrostatic ligand-protein interactions in the docked
      binding modes and on the quantum chemically derived charges of the triazole ring
      demonstrated a good explanatory power for the observed activities.

PMID- 22616903
TI  - Cold stress selectively unsilences tandem repeats in heterochromatin associated
      with accumulation of H3K9ac.
AB  - Knobs are cytologically observable major interstitial heterochromatin present on
      maize nuclei, which consist of highly tandem-repetitive elements that are always
      silenced. Here we investigated the genome-wide change of H3K9ac, an active
      chromatin mark, during cold stress using chromatin immunoprecipitation sequencing
      (ChIP-Seq) and identified differential cold-induced H3K9ac enrichment at
      repetitive sequences in maize. More detailed analysis of two knob-associated
      tandem-repetitive sequences, 180-bp and TR-1, demonstrated that cold activated
      their transcription and this cold-induced transcriptional activation of
      repetitive sequences is selective, transient, and associated with an increase in
      H3K9ac and a reduction in DNA methylation and H3K9me2. Furthermore, knob sequence
      expression is accompanied by localized chromatin remodelling and silencing is
      recovered upon prolonged treatment. In addition, no evidence of copy number
      change and rearrangement of these repetitive elements are found in plants
      subjected to cold stress. These results suggest that cold-mediated unsilencing of
      heterochromatic tandem-repeated sequences, accompanied with epigenetic
      regulation, might play an important role in the adaptation of plants to cold
      stimuli.

PMID- 22616904
TI  - Degradation of organic dyes via bismuth silver oxide initiated direct oxidation
      coupled with sodium bismuthate based visible light photocatalysis.
AB  - Organic dye degradation was achieved via direct oxidation by bismuth silver oxide
      coupled with visible light photocatalysis by sodium bismuthate. Crystal violet
      dye decomposition by each reagent proceeded via two distinct pathways, each
      involving different active oxygen species. A comparison of each treatment method
      alone and in combination demonstrated that using the combined methods in sequence
      achieved a higher degree of degradation, and especially mineralization, than that
      obtained using either method alone. In the combined process direct oxidation acts
      as a pretreatment to rapidly bleach the dye solution which substantially
      facilitates subsequent visible light photocatalytic processes. The integrated
      sequential direct oxidation and visible light photocatalysis are complementary
      manifesting a > 100% increase in TOC removal, compared to either isolated method.
      The combined process is proposed as a novel and effective technology based on one
      primary material, sodium bismuthate, for treating wastewaters contaminated by
      high concentrations of organic dyes.

PMID- 22616905
TI  - Transferrin-conjugated micelles: enhanced accumulation and antitumor effect for
      transferrin-receptor-overexpressing cancer models.
AB  - As the transport protein for iron, transferrin can trigger cellular endocytosis
      once binding to its receptor (TfR) on the cell membrane. Using this property, we
      conjugated transferrin onto the surface of biodegradable polymeric micelles
      constructed from amphiphilic block copolymers. The core of micelle was either
      labeled with a near-infrared dye (NIR) or conjugated with a chemotherapeutic drug
      paclitaxel (PTX) to study the biodistribution or antitumor effect in nude mice
      bearing subcutaneous TfR-overexpressing cancers. DLS and TEM showed that the
      sizes of Tf-conjugated and Tf-free micelles were in the range of 85-110 nm.
      Confocal laser scanning microscopy and flow cytometry experiments indicated that
      the uptake efficiency of the micelles by the TfR-overexpressing cells was
      enhanced by Tf conjugation. Semiquantitative analysis of the NIR signals
      collected from the tumor site showed that the maximum accumulation was achieved
      at 28 h in the M(NIR) group, while at 22 h in Tf-M(NIR) groups; and the area
      under the intensity curve in the Tf-M(NIR) groups was more than that in M(NIR)
      group. Finally, the tumor inhibition effects of targeting micelles were studied
      with the gastric carcinoma model which overexpressed TfR. The analysis of tumor
      volumes and the observation of H&E-stained tumor sections showed that Tf-M(PTX)
      had the best antitumor effect compared with the control groups (saline, PTX, and
      M(PTX)). The results of this study demonstrated the potential application of Tf
      conjugated polymeric micelles in the treatment of TfR-overexpressing cancers. 

PMID- 22616906
TI  - Innate immunity to influenza in chronic airways diseases.
AB  - Influenza presents a unique human infectious disease that has a substantial
      impact on the public health, in general, and especially for those with chronic
      airways diseases. People with asthma and chronic obstructive pulmonary disease
      (COPD) are particularly vulnerable to influenza infection and experience more
      severe symptoms with the worsening of their pre-existing conditions. Recent
      advances in reverse genetics and innate immunity has revealed several influenza
      virulence factors and host factors involved in influenza pathogenesis and the
      immune responses to infection. Early innate immunity plays a critical role of
      limiting viral infection and spread; however, the underlying mechanisms that lead
      to enhanced susceptibility to influenza infection and severe symptoms in those
      with asthma and COPD to infection remain un-investigated. This review will
      explore the importance of early innate antiviral responses to influenza infection
      and how these responses are altered by influenza virus and in those with chronic
      airways diseases.

PMID- 22616907
TI  - Prevalence of soft tissue oral lesion in elderly and its relations with
      deleterious habits.
AB  - INTRODUCTION: With ageing, the oral mucosa becomes more susceptible to external
      stimuli. OBJECTIVE: To investigate the prevalence of soft tissue oral lesion in
      elderly and its relations with deleterious habits. MATERIALS AND METHODS: It was
      a quantitative research conducted at the dental clinic of UNIFOR, Fortaleza-CE,
      in the period from 1998 to 2006. The sample consisted of all 756 records of the
      elderly, and the data were processed by SPSS 15.0 (SPSS, Inc., Chicago, IL, USA).
      RESULTS: The majority (63.0) were women, age 60-92, mean age 67 +/- 6. The most
      significant proportions were married (48.4%), retired (42.3%) and incomplete
      primary school (31.5%). It was found a prevalence of 18.3% of oral lesions, with
      the risk being 1.6 times higher (p = 0.030) among youngest (up to 65 years) and
      1.7 times higher among smokers (p = 0.048). Although this risk is 1.6 times
      higher among those who drank alcohol, it was not statistically significant (p =
      0.122). CONCLUSION: The elderly showed a high prevalence of oral lesion, being
      the youngest, the smokers and the alcohol consumers those most vulnerable to the
      emergence of these diseases. Dental services need to implement programs of
      elderly care and health education, essential to clarify the risks and their
      associations with oral diseases, aiming to promote health.

PMID- 22616908
TI  - Effects of systemic sitafloxacin on periodontal infection control in elderly
      patients.
AB  - OBJECTIVE: To evaluate the microbiological and clinical effects of the systemic
      administration of sitafloxacin (STFX) on periodontal pockets in elderly patients
      receiving supportive periodontal therapy (SPT). BACKGROUND: Periodontitis is a
      risk factor for atherosclerosis. Better periodontal health contributes to reduce
      atherosclerosis-related diseases in elderly population. MATERIALS AND METHODS:
      Forty-four patients undergoing SPT were randomly assigned to two groups: a test
      group took 100 mg/day of STFX for five consecutive days, or a control group
      received scaling and root planing (SRP) under local anaesthesia. Microbiological
      and clinical parameters were examined at baseline and at 1 and 3 months after
      therapy. RESULTS: The presence of Porphyromonas gingivalis, Treponema denticola
      and Tannerella forsythia was significantly reduced at 1 month after treatment in
      both groups. The median reductions of the bacteria between the baseline and 1
      month were 3.08 and 2.54% in the STFX- and SRP-treated groups, respectively. Both
      treatments significantly decreased the probing depth at 1 and 3 months compared
      to the baseline. CONCLUSION: The systemic administration of STFX is effective at
      improving periodontal health during SPT and could be an alternative to SRP for
      elderly patients who cannot undergo anaesthesia or are at risk of tissue injury.

PMID- 22616909
TI  - Outcome of implant-supported overdenture treatment--a survey of 58 patients.
AB  - OBJECTIVE: The aim of this follow-up study was to evaluate the long-term outcome
      of implant-supported or implant-retained mandibular overdenture treatment.
      MATERIAL AND METHODS: Altogether 112 patients treated with implant-supported
      overdentures between 1985 and 2004 were invited to the follow-up and 58 attended
      the clinical examination. The total amount of implants examined and still in use
      was 197. The average number of implants installed was three (range 2-4), and the
      mean length of the implants was 12 mm (range 8-21 mm). There were altogether 48
      overdentures with a bar connection and 10 with a ball connection. RESULTS: The
      most frequent prosthetic complications were technical: loosening of the retentive
      mechanism (39.7%) and breakage of the matrices (5.2%). The most common peri
      implant soft-tissue findings were bleeding and slight hyperplasia. The implant
      supported overdentures of 19 patients (32.8%) had been renewed, while 39 patients
      (67.2%) still used their original overdentures, of which the oldest was 20 years
      old. CONCLUSION: The results of this long-term follow-up study show that the
      outcome of implant-supported mandibular overdenture treatment was excellent. The
      patients were satisfied with the treatment, regardless of the attachment type
      used. Removable overdentures are more easy to clean and can be cleaned outside
      the patient's mouth, whereas fixed-implant full-arch dentures in the edentulous
      mandible require much more time-consuming hygiene. This kind of overdenture
      treatment is suitable also in the elderly, even though their ability to practice
      appropriate oral hygiene might be decreased.

PMID- 22616910
TI  - Discussions on oral health care among elderly Chinese immigrants in Melbourne and
      Vancouver.
AB  - BACKGROUND: This study explored how elderly Chinese immigrants value and relate
      to how acculturation influences oral health and subsequent service use. METHODS:
      Elders who had immigrated to Melbourne and Vancouver within the previous 15 years
      were recruited from local community centres and assigned to focus groups of 5-7
      participants in Vancouver (4 groups) or Melbourne (5 groups). RESULTS: Following
      an iterative process of thematic analysis, the discussions revealed that
      immigrants care about the comfort and appearance of their teeth, and they value
      Western dentistry as a supplement to traditional remedies, but they have
      difficulty getting culturally sensitive information about oral health care.
      Accessing dentistry, they explained, is distressing because of language problems
      and financial costs that impose on their children. Consequently, many immigrants
      obtain dental treatment in China when they return for occasional visits. They
      felt that separation of dentistry from national health care programmes in Canada
      and Australia disregards natural links between oral health and general health.
      CONCLUSIONS: The similarity of concerns in both cities suggests that
      dissemination of information and availability of services are the important
      themes influencing oral health, and that, beliefs developed over a lifetime play
      an important role in interpreting oral health in the host country.

PMID- 22616911
TI  - Cancer therapy monitoring in xenografts by quantitative analysis of circulating
      tumor DNA.
AB  - CONTEXT: Circulating tumor DNA (ctDNA) is a promising biomarker in cancer.
      MATERIALS AND METHODS: We generated xenograft models of cancer and detected ctDNA
      in plasma by qRCR targeting human AluJ sequences. RESULTS: Our assay reached
      single cell sensitivity in vitro and a correlation between ctDNA amount and tumor
      size was observed in vivo. Treatment with a mitogen activated protein kinase
      kinase (MEK)-inhibitor (BAY 869766) reduced ctDNA levels. Using this assay, we
      also confirmed that high levels of cell-free DNA are found in cancer patients
      compared to healthy individuals. DISCUSSION AND CONCLUSION: We show that ctDNA
      may be useful biomarker for monitoring tumor growth and treatment response.

PMID- 22616912
TI  - Disulfide-containing brushed polyethylenimine derivative synthesized by click
      chemistry for nonviral gene delivery.
AB  - Polyaspartamide-based disulfide-containing brushed polyethylenimine derivatives
      P(Asp-Az)X-SS-PEIs were synthesized via click chemistry and evaluated as nonviral
      gene delivery carrier. First, azide-functional poly(aspartic acid) derivatives
      with various azide-group densities and monoalkyne-terminated PEI with disulfide
      linkages were synthesized. Then, click reaction between the azide-functional
      poly(aspartic acid) derivative as main chain and the monoalkyne-terminated PEI as
      branched chain resulted in high-molecular-weight disulfide-containing brushed PEI
      derivative. The structure of obtained polymers was confirmed by (1)H NMR and
      FTIR. It was shown that the disulfide-containing P(Asp-Az)X-SS-PEIs were able to
      bind plasmid DNA and condense DNA into small positive nanoparticles. The
      reduction-sensitivity of the P(Asp-Az)X-SS-PEI/DNA polyplexes was confirmed by
      gel retardation assay and dynamic light scattering (DLS) in the presence of DTT.
      In vitro experiments revealed that the reducible P(Asp-Az)X-SS-PEI not only had
      much lower cytotoxicity, but also posed high transfection activity (both in the
      presence and absence of serum) as compared to the control nondegradable 25 kDa
      PEI. This study indicates that a reducibly degradable brushed polymer P(Asp-Az)X
      SS-PEI composed of low-molecular-weight (LMW) PEI via a disulfide-containing
      linkage can be a promising gene delivery carrier. 

PMID- 22616913
TI  - No effect of the FitFor2 exercise programme on blood glucose, insulin
      sensitivity, and birthweight in pregnant women who were overweight and at risk
      for gestational diabetes: results of a randomised controlled trial.
AB  - OBJECTIVE: To evaluate the effectiveness of an exercise programme for pregnant
      women who were overweight or obese and at risk for gestational diabetes mellitus
      (GDM). DESIGN: Randomised controlled trial. SETTING: Hospitals and midwifery
      practices in the Netherlands. POPULATION: Pregnant women who were overweight or
      obese and at risk for GDM between 2007 and 2011. METHODS: Normal care was
      compared with an exercise training programme during pregnancy. The training
      consisted of aerobic and strength exercises, and was aimed at improving maternal
      fasting blood glucose, insulin sensitivity, and birthweight. Linear regression
      analyses were performed to determine the effects. MAIN OUTCOME MEASURES: Maternal
      outcome measures were fasting blood glucose (mmol/l), fasting insulin (pmol/l)
      and HbA1c (%), body weight (kg), body mass index (kg/m(2) ), and daily physical
      activity (minute/week). Offspring outcome measures were birthweight and fetal
      growth. RESULTS: A total of 121 women were randomly allocated to either a control
      (n = 59) or an intervention (n = 62) group. Intention-to-treat analysis showed
      that the exercise programme did not reduce maternal fasting blood glucose levels
      nor insulin sensitivity. Also, no effect was found on birthweight. CONCLUSIONS:
      The exercise intervention performed over the second and third trimester of
      pregnancy had no effects on fasting blood glucose, insulin sensitivity, and
      birthweight, most probably because of low compliance. The high prevalence of
      women at risk for GDM calls for further research on possible interventions that
      can prevent GDM, and other types of interventions to engage this target group in
      physical activity and exercise.

PMID- 22616914
TI  - Soft nanotube hydrogels functioning as artificial chaperones.
AB  - Self-assembly of rationally designed asymmetric amphiphilic monomers in water
      produced nanotube hydrogels in the presence of chemically denatured proteins
      (green fluorescent protein, carbonic anhydrase, and citrate synthase) at room
      temperature, which were able to encapsulate the proteins in the one-dimensional
      channel of the nanotube consisting of a monolayer membrane. Decreasing the
      concentrations of the denaturants induced refolding of part of the encapsulated
      proteins in the nanotube channel. Changing the pH dramatically reduced
      electrostatic attraction between the inner surface mainly covered with amino
      groups of the nanotube channel and the encapsulated proteins. As a result, the
      refolded proteins were smoothly released into the bulk solution without specific
      additive agents. This recovery procedure also transformed the encapsulated
      proteins from an intermediately refolding state to a completely refolded state.
      Thus, the nanotube hydrogels assisted the refolding of the denatured proteins and
      acted as artificial chaperones. Introduction of hydrophobic sites such as a
      benzyloxycarbony group and a tert-butoxycarbonyl group onto the inner surface of
      the nanotube channels remarkably enhanced the encapsulation and refolding
      efficiencies based on the hydrophobic interactions between the groups and the
      surface-exposed hydrophobic amino acid residues of the intermediates in the
      refolding process. Refolding was strongly dependent on the inner diameters of the
      nanotube channels. Supramolecular nanotechnology allowed us to not only precisely
      control the diameters of the nanotube channels but also functionalize their
      surfaces, enabling us to fine-tune the biocompatibility. Hence, these nanotube
      hydrogel systems should be widely applicable to various target proteins of
      different molecular weights, charges, and conformations.

PMID- 22616915
TI  - Halodiazophosphonates, a new class of diazo compounds for the diastereoselective
      intermolecular Rh(II) catalyzed cyclopropanation.
AB  - (Halodiazomethyl)phosphonates 2A-C have been generated by a one-pot procedure via
      a clean, efficient, and rapid deprotonation/electrophilic halogenation sequence
      from diethyl diazomethylphosphonate 1 (EDP). Subsequent intermolecular Rh(II)
      catalyzed cyclopropanation afforded the corresponding halocyclopropylphosphonates
      3-10 in moderate to high yields and high diastereomeric ratios. Catalyst loadings
      down to 0.1 mol % as well as clean and selective product formation were achieved.

PMID- 22616916
TI  - Family-school nurse partnership in primary school health care.
AB  - BACKGROUND: The foundation of the health and well-being of a child in primary
      school age is the family. To promote the child's comprehensive health, we must
      develop the cooperation between the family and the primary school nurse. AIM: The
      aim of the study was to develop a family nursing oriented substantive theory of
      cooperation between primary school nurses and families. METHOD: The study used
      grounded theory based on Straussian principles. Data were collected from sixth
      graders (N = 22) using group discussions. Interviews were conducted with parents
      (N = 19), and the views of school nurses (N = 20) on their cooperation with
      families were obtained via free form essays. FINDINGS: The core concept of the
      theory describing cooperation between primary school nurses and families is
      problem-based communication. As a result of the analysis, nine-2-dimensional
      concepts were formed to describe this cooperation. The theory is structured
      further by four dimensions, which contain concepts explaining them and which also
      describe the relationships between the different concepts. These dimensions are
      the meeting between the school nurse and the family, mutual exchange of
      information, attending to the child's health monitoring and being at school for
      the child and family. The substantive theory describing cooperation between the
      primary school nurse and family entails the concepts formed in the analysis,
      their interrelationships, as well as, the core concept. CONCLUSIONS: Primary
      school nurses can apply the resulting theory while working with families and
      while developing this cooperation. This theory can also be implemented in
      developing nursing education.

PMID- 22616917
TI  - Balance of nanostructure and bimetallic interactions in Pt model fuel cell
      catalysts: in situ XAS and DFT study.
AB  - We have studied the effect of nanostructuring in Pt monolayer model
      electrocatalysts on a Rh(111) single-crystal substrate on the adsorption strength
      of chemisorbed species. In situ high energy resolution fluorescence detection X
      ray absorption spectroscopy at the Pt L(3) edge reveals characteristic changes of
      the shape and intensity of the "white-line" due to chemisorption of atomic
      hydrogen (H(ad)) at low potentials and oxygen-containing species (O/OH(ad)) at
      high potentials. On a uniform, two-dimensional Pt monolayer grown by Pt
      evaporation in ultrahigh vacuum, we observe a significant destabilization of both
      H(ad) and O/OH(ad) due to strain and ligand effects induced by the underlying
      Rh(111) substrate. When Pt is deposited via a wet-chemical route, by contrast,
      three-dimensional Pt islands are formed. In this case, strain and Rh ligand
      effects are balanced with higher local thickness of the Pt islands as well as
      higher defect density, shifting H and OH adsorption energies back toward pure Pt.
      Using density functional theory, we calculate O adsorption energies and
      corresponding local ORR activities for fcc 3-fold hollow sites with various local
      geometries that are present in the three-dimensional Pt islands.

PMID- 22616918
TI  - Inter- and intraspecies transmission of canine influenza virus (H3N2) in dogs,
      cats, and ferrets.
AB  - BACKGROUND: The emergence of zoonotic viruses in domestic animals is a
      significant public health concern. Canine influenza virus (CIV) H3N2 is a virus
      that can infect companion animals and is, therefore, a potential public health
      concern. OBJECTIVE: This study investigated the inter- and intraspecies
      transmission of CIV among dogs, cats, and ferrets, under laboratory conditions,
      to determine whether transmission of the virus was possible between as well as
      within these domestic animal species. METHOD: The transmission routes for inter-
      and intraspecies transmission were airborne and direct contact, respectively.
      Transmission was conducted through intranasal infection of dogs followed by
      exposure to either cats or ferrets and by comingling infected and naive animals
      of the same species. RESULTS: The interspecies transmission of CIV H3N2 via
      airborne was only observed from dogs to cats and not from dogs to ferrets.
      However, direct intranasal infection of either cats or ferrets with CIV could
      induce influenza-like clinical signs, viral shedding, and serological responses.
      Additionally, naive cats and ferrets could be infected by CIV via direct contact
      with infected animals of the same species. CONCLUSION: Cats appear to be another
      susceptible host of CIV H3N2, whereas ferrets are not likely natural hosts. The
      molecular-based mechanism of interspecies and intraspecies transmission of CIV
      H3N2 should be further studied.

PMID- 22616919
TI  - Bone marrow-derived, alternatively activated macrophages enhance solid tumor
      growth and lung metastasis of mammary carcinoma cells in a Balb/C mouse
      orthotopic model.
AB  - INTRODUCTION: Tumor-associated macrophages, which are derived from the
      infiltration of circulating bone marrow-derived monocytes, consist primarily of a
      polarized M2 macrophage (M2-Mphi) population and are associated with poor
      prognosis in various cancers. In the present study, we attempted to assess
      whether M2-Mphis derived from bone marrow stimulate the promotion and progression
      of mammary tumors. METHODS: 4T1 murine mammary carcinoma cells were injected
      either alone or coupled with M2-Mphis into the mammary fat pads of syngeneic
      female Balb/C mice. M2-Mphis were prepared by treating monocytes isolated from
      female Balb/C mouse bone marrow with IL-4. Tumor cell growth was determined using
      an in vivo imaging system and the expression of cell proliferation-related,
      angiogenesis-related, and lymphangiogenesis-related proteins in tumor tissues was
      immunohistochemically analyzed. To evaluate the effects of the crosstalk between
      4T1 cells and M2-Mphis on the secretion and mRNA expression of cytokines and the
      migration of monocytes, 4T1 cells and M2-Mphis were co-cultured and cytokine
      antibody array, real-time RT-PCR, and trans-well migration assays were conducted.
      RESULTS: The co-injection of M2-Mphis into the mammary fat pads of mice increased
      solid tumor growth and lung metastasis of 4T1 cells as well as the infiltration
      of CD45+ leukocytes into tumor tissues. The proportions of Ki-67+ proliferating
      cells and the expression of hypoxia inducible factor-1alpha, vascular endothelial
      cell growth factor A, CD31, vascular endothelial cell growth factor C, and
      lymphatic vessel endothelial receptor-1 were increased significantly in the tumor
      tissues of mice co-injected with 4T1 cells and M2-Mphis. The in vitro results
      revealed that the proliferation of 4T1 cells, the migration of monocytes, and the
      secretion of granulocyte colony-stimulating factor, IFNgamma, IL-1alpha, IL-2, IL
      16, IFNgamma-induced protein-10, keratinocyte-derived chemokine, macrophage
      colony-stimulating factor, monocyte chemotactic protein-1, macrophage
      inflammatory protein-1alpha, and RANTES were increased when 4T1 cells were co
      cultured with M2-Mphis, as compared with when the 4T1 cells were cultured alone.
      CONCLUSION: The crosstalk between 4T1 cells and M2-Mphis increased the production
      of cytokines, which may have induced immune cell infiltration into tumor tissues,
      tumor cell proliferation, angiogenesis, and lymph angiogenesis, thereby
      increasing solid tumor growth and lung metastasis.

PMID- 22616920
TI  - Long-term cognitive outcomes of infants born moderately and late preterm.
AB  - AIM: To investigate whether infants born late preterm have poorer cognitive
      outcomes than term-born infants. METHOD: A cohort study based on the Avon
      Longitudinal Study of Parents and Children. Cognitive measures were assessed
      between the ages of 8 and 11 years. Exposure groups were defined as moderate/late
      preterm (32-36 weeks' gestation) or term (37-42 wk). Regression models were used
      to investigate the association between gestational age and IQ. RESULTS: Seven
      hundred and forty-one infants (5.4% of total eligible population; 422 males, 319
      females; mean (SD) birthweight 2495 g [489]) were born between 32 and 36 weeks'
      gestation. The analysis was based on 6957 infants with IQ data at age 11 (50% of
      eligible infants). In the adjusted model, children born moderately and late
      preterm had similar IQ scores to peers born at term (mean difference [95%
      confidence interval] -0.18 [-1.88 to 1.52]). However, the preterm infants had a
      higher risk of having special educational needs at school (odds ratio 1.56 [1.18
      2.07]). INTERPRETATION: Despite an increased risk of special educational needs,
      there is little evidence of a reduction in IQ, memory, or attention measures at
      school age in children born between 32 and 36 weeks' gestation. Although
      interpretation is limited by the amount of missing data, further work is needed
      to identify why these infants have increased educational needs.

PMID- 22616921
TI  - The effect of pH and time on the extractability and speciation of uranium(VI)
      sorbed to SiO2.
AB  - The effect of pH and contact time on uranium extractability from quartz surfaces
      was investigated using either acidic or carbonate (CARB) extraction solutions,
      time-delayed spikes of different U isotopes ((238)U and (233)U), and liquid
      helium temperature time-resolved laser-induced fluorescence spectroscopy (TRLFS).
      Quartz powders were reacted with (238)U(VI) bearing solutions equilibrated with
      atmospheric CO(2) at pH 6, 7, and 8. After 42 days, the suspensions were spiked
      with (233)U(VI) and reacted for an additional 7 days. Sorbed U was then extracted
      with either dilute nitric acid or CARB. For the CARB, but not the acid,
      extraction there was a systematic decrease in extraction efficiency for both
      isotopes from pH 6 to 8, which was mimicked by less desorption of (238)U, after
      the (233)U spike, from pH 6 to 8. The efficiency of (233)U extraction was
      consistently greater than that of (238)U, indicating a strong temporal component
      to the strength of U association with the surface that was accentuated with
      increasing pH. TRLFS revealed a strong correlation between CARB extraction
      efficiency and sorbed U speciation as a function of pH and time. Collectively,
      the observations show that aging and pH are critical factors in determining the
      form and strength of uranium-silica interactions.

PMID- 22616922
TI  - The 7/8 crown: a lost art.
AB  - Historically, the longevity of teeth restored with gold inlays, onlays, crowns,
      and partial veneer restorations is excellent. However, in-office computer-aided
      design and computer-aided manufacturing restorations, laboratory-constructed all
      ceramic bonded restorations, and conventional ceramo-metal restorations are more
      common. The high price of gold, the difficulty of the preparation, and the fact
      that most dental schools are de-emphasizing the teaching of partial veneer
      restorations has created a situation whereby the 7/8 crown is rarely viewed as
      the treatment of choice. Time and experience will determine if the new ceramic
      materials, along with the all-important bonding agents, can achieve the success
      of a well-done, all-gold restoration.

PMID- 22616923
TI  - Influence of surface roughness on mechanical properties of two computer-aided
      design/computer-aided manufacturing (CAD/CAM) ceramic materials.
AB  - The aim of this study was to evaluate the influence of surface roughness on
      surface hardness (Vickers; VHN), elastic modulus (EM), and flexural strength
      (FLS) of two computer-aided design/computer-aided manufacturing (CAD/CAM) ceramic
      materials. One hundred sixty-two samples of VITABLOCS Mark II (VMII) and 162
      samples of IPS Empress CAD (IPS) were ground according to six standardized
      protocols producing decreasing surface roughnesses (n=27/group): grinding with 1)
      silicon carbide (SiC) paper #80, 2) SiC paper #120, 3) SiC paper #220, 4) SiC
      paper #320, 5) SiC paper #500, and 6) SiC paper #1000. Surface roughness (Ra/Rz)
      was measured with a surface roughness meter, VHN and EM with a hardness
      indentation device, and FLS with a three-point bending test. To test for a
      correlation between surface roughness (Ra/Rz) and VHN, EM, or FLS, Spearman rank
      correlation coefficients were calculated. The decrease in surface roughness led
      to an increase in VHN from (VMII/IPS; medians) 263.7/256.5 VHN to 646.8/601.5
      VHN, an increase in EM from 45.4/41.0 GPa to 66.8/58.4 GPa, and an increase in
      FLS from 49.5/44.3 MPa to 73.0/97.2 MPa. For both ceramic materials, Spearman
      rank correlation coefficients showed a strong negative correlation between
      surface roughness (Ra/Rz) and VHN or EM and a moderate negative correlation
      between Ra/Rz and FLS. In conclusion, a decrease in surface roughness generally
      improved the mechanical properties of the CAD/CAM ceramic materials tested.
      However, FLS was less influenced by surface roughness than expected.

PMID- 22616924
TI  - In vitro marginal fit of three all-ceramic crown systems before and after
      cementation.
AB  - STATEMENT OF THE PROBLEM: Full-coverage all-ceramic restorations are widely used.
      The impact of various classifications of luting agent on marginal discrepancies
      is not well understood. PURPOSE: The purpose of this study was to evaluate the
      cervical fit of all ceramic crowns (IPS e.maxPress, Cergogold, and In Ceram) on
      bovine teeth with two luting agents before and after cementation. MATERIALS AND
      METHODS: Ninety bovine incisors were embedded in resin. The coronal portions of
      the teeth were prepared to receive full-coverage crowns. Thirty crowns of 7.0 +/-
      0.5 mm height, 8.0 mm cervical diameter, and 4.2 mm incisal diameter were
      fabricated for each ceramic system. The crowns were seated on the teeth, and the
      marginal discrepancy was measured using a measuring microscope. Then, 15 crowns
      of each ceramic system were luted on the teeth with resin cement (Variolink II)
      or resin-modified glass ionomer cement (Rely X luting), and the marginal
      discrepancy was measured. The results were submitted to analysis of variance, t
      test and Tukey's test (p<0.05). RESULTS: The three ceramic systems showed
      cervical fits after cementation statistically inferior to cervical fits before
      cementation for the two cements. The IPS e.maxPress showed values for cervical
      fit statistically superior to Cergogold before cementation. No statistically
      significant difference was found between IPS e.maxPress and In Ceram and In Ceram
      and Cergogold. After cementation, no statistically significant difference was
      found for the three ceramics systems when luted with resin or resin-modified
      glass ionomer luting agents. CONCLUSIONS: Within the limitations of this study,
      it can be concluded that both cements studied increase the marginal discrepancy
      between the crown and the preparation for the three ceramic systems evaluated.

PMID- 22616925
TI  - The effect of prophylaxis method on microtensile bond strength of indirect
      restorations to dentin.
AB  - The aim of this study was to evaluate the effect of different materials used for
      dentin prophylaxis on the microtensile bond strengths (MUTBS) of adhesively
      cemented indirect composite restorations. Sixty bovine incisors had the buccal
      surface ground with wet #600-grit silicon carbide abrasive paper to obtain a flat
      exposed superficial dentin and were submitted to different prophylaxis protocols,
      as follows: 3% hydrogen peroxide (HydP); 0.12% chlorhexidine (Chlo); sodium
      bicarbonate jet (SodB); 50-MUm aluminum oxide air abrasion (AirA); pumice paste
      (PumP), and control group-water spray (Cont). After prophylaxis protocols a resin
      composite block (3.0 mm * 5.0 mm * 5.0 mm) was adhesively cemented using dual
      resin cement (Rely X ARC). After 24 hours of water storage, specimens were
      serially sectioned perpendicular to the bonded interface into 1-mm-thick slices.
      Each specimen was trimmed with a diamond bur to an hourglass shape with a cross
      sectional area of approximately 1.0 mm(2) at the bonded area. Specimens were
      tested (MUTBS) at 0.5 mm/min using a universal testing machine. Scanning electron
      microscopy was used to examine the effects of prophylaxis techniques on dentin.
      Bond strength data (MPa) were analyzed by one-way analysis of variance and
      failure mode by Fisher test (alpha=0.05). MUTBS data, means (SD), were (different
      superscripted letters indicate statistically significant differences): AirA, 25.2
      (7.2)(a); PumP, 24.1 (7.8)(a); Chlo, 21.5 (5.6)(a); Cont, 20.6 (8.1)(a); HydP(,)
      15.5 (7.6)(b); and SodB(,) 11.5 (4.4)(c). The use of aluminum oxide air abrasion,
      pumice paste, and chlorhexidine before acid etching did not significantly affect
      MUTBS to dentin; however, the use of hydrogen peroxide and sodium bicarbonate jet
      significantly reduced MUTBS.

PMID- 22616926
TI  - The effects of scaling and root planing on the marginal gap and microleakage of
      indirect composite crowns prepared with different finish lines: an in vitro
      study.
AB  - The present in vitro study aimed to assess the effects of root surface mechanical
      instrumentation on the marginal integrity and adaptation of resin composite
      crowns. The following null hypotheses were tested: no differences exist between
      finish line and 1) marginal gap or 2) marginal microleakage before and after
      manual mechanical periodontal maintenance. A total of 56 intact human mandibular
      molars were randomly distributed into four groups and subjected to standardized
      tooth preparations for indirect composite crowns with different marginal finish
      lines (90 degrees  shoulder, beveled 90 degrees  shoulder, feather edge,
      chamfer). One-half of the specimens was used as a control and remained untreated,
      and the remaining half was subjected to root surface procedures simulating five
      years of semestral mechanical supportive periodontal treatment. The marginal gap
      and microleakage were evaluated and statistically analyzed. The specimens used as
      controls showed lower mean marginal gaps than those subjected to the simulated
      periodontal treatment, whereas the latter showed lower microleakage than the
      control crowns. Statistically significant differences were recorded for both the
      experimental variables. The root surface procedures resulted in altered surfaces
      of the composite crowns. The marginal gap increased after the treatment, whereas
      the marginal microleakage was reduced. The 90 degrees  shoulder and the chamfer
      preparation could be considered a viable option to fabricate composite crowns,
      but the beveled 90 degrees  shoulder and the feather edge should not be
      recommended.

PMID- 22616927
TI  - Clinical comparative study of the effectiveness of and tooth sensitivity to 10%
      and 20% carbamide peroxide home-use and 35% and 38% hydrogen peroxide in-office
      bleaching materials containing desensitizing agents.
AB  - The aim of this study was to compare the effectiveness of and tooth sensitivity
      to 10% and 20% carbamide peroxide (CP) home-use bleaching agents and 35% and 38%
      hydrogen peroxide (HP) in-office bleaching agents, all of which contain
      desensitizing agents, in a clinical trial. Four agents were evaluated: 10% CP and
      20% CP (Opalescence PF 10% and Opalescence PF 20%, Ultradent, both with 0.5%
      potassium nitrate and 0.11% fluoride ions), 38% HP (Opalescence Boost PF,
      Ultradent, with 3% potassium nitrate and 1.1% fluoride ions), and 35% HP (Pola
      Office, SDI, with potassium nitrate). The initial screening procedure included
      100 volunteers, aged 18 to 42, with no previous sensitivity or bleaching
      treatment and with any tooth shade. Volunteers were randomly assigned among the
      technique/bleaching agent groups. A run-in period was performed 1 week before the
      beginning of the bleaching treatment. For the home-use bleaching technique, each
      volunteer was instructed to dispense gel (10% CP or 20% CP) into the trays and
      then insert them into his or her mouth for at least two hours per night for three
      weeks. For the in-office bleaching technique, the bleaching agents (38% HP or 35%
      HP) were prepared and used following the manufacturer's instructions, with three
      applications performed in each session. Three sessions were carried out with an
      interval of seven days between each session. The participants were evaluated
      before, at one week, two weeks, and three weeks after the beginning of the
      bleaching treatment, and again one and two weeks after the bleaching treatment
      ended. A shade guide (Vita Classical, Vita) was used by a blinded examiner to
      perform shade evaluations before bleaching and two weeks after the end of
      bleaching. At the time of the shade evaluations, tooth sensitivity was also
      recorded by asking the volunteers to classify the sensitivity during bleaching
      treatment as absent, mild, moderate, or severe. The present study found that
      13.8% of the volunteers withdrew from the study due to tooth sensitivity, and
      43.2% of the participants experienced some type of sensitivity during bleaching
      treatment. The chi(2) test showed that there was a significant prevalence of
      tooth sensitivity during bleaching treatment using the home-use 20% CP agent,
      with 71.4% of volunteers reporting any level of tooth sensitivity (p=0.0032). A
      low prevalence of tooth sensitivity was observed for volunteers who used the in
      office 38% HP agent (15.0%). The Wilcoxon test (p<0.05) showed that all of the
      bleaching treatments were effective in bleaching teeth and that there were no
      differences between the final color shade results among the treatments (Kruskal
      Wallis, p<0.05). This study showed that 43.2% of all the volunteers experienced
      mild or moderate tooth sensitivity during the treatment with bleaching agents. A
      higher prevalence of tooth sensitivity was observed for 71.4% of the volunteers
      who used the 20% CP home-use bleaching agent, which may be ascribed to the
      peroxide concentration and/or the time/length the agent was in contact with the
      dental structures.

PMID- 22616928
TI  - Comparative evaluation of microleakage of silorane-based composite and nanohybrid
      composite with or without polyethylene fiber inserts in class II restorations: an
      in vitro study.
AB  - AIM: To evaluate microleakage between nanocomposite and silorane composite in
      class II restorations with or without a polyethylene fiber insert. METHODOLOGY:
      Standardized class II cavities were prepared on extracted molars and randomly
      divided into 4 groups (n=20 each): group 1, Ceram X mono; group 2, Ceram X mono +
      Ribbond; group 3, Filtek P90; and Group 4, Filtek P90 + Ribbond. All specimens
      were subjected to a thermocycling regime, immersed in 2% methylene blue dye for
      24 hours, sectioned longitudinally, and examined under a stereomicroscope to
      assess dye penetration on a six-point scale. The score data were subjected to
      statistical analysis whereby Kruskal-Wallis analysis of variance was used for
      multiple group comparisons and the Mann-Whitney test for groupwise comparisons at
      a significance level of p<=0.05. RESULTS: A statistically significant decrease in
      microleakage was found when Ribbond fiber was used with nanoceramic and silorane
      composite. A highly significant decrease in microleakage scores was found in
      silorane composite when compared to nanoceramic composite. CONCLUSION: Use of
      polyethylene fiber and silorane composite reduces microleakage in class II
      composite restorations with gingival margins below the cemento-enamel junction.

PMID- 22616930
TI  - Repair of dimethacrylate-based composite restorations by a silorane-based
      composite: a one-year randomized clinical trial.
AB  - PURPOSE: To investigate clinical performance of a low-shrinkage silorane-based
      composite resin when used for repairing conventional dimethacrylate-based
      composite restorations. BACKGROUND: Despite the continued development of resin
      based materials, polymerization shrinkage and shrinkage stress still require
      improvement. A silorane-based monomer system was recently made available for
      dental restorations. This report refers to the use of this material for making
      repairs and evaluates the clinical performance of this alternative treatment.
      MATERIALS AND METHODS: One operator repaired the defective dimethacrylate-based
      composite resin restorations that were randomly assigned to one of two treatment
      groups: control (n=50) repair with Adper SE Plus (3M/ESPE) and Filtek P60
      Posterior Restorative (3M/ESPE), and test (n=50) repair with P90 System Adhesive
      Self-Etch Primer and Bond (3M/ESPE) and Filtek P90 Low Shrink Posterior
      Restorative (3M/ESPE). After one week, restorations were finished and polished.
      Two calibrated examiners (Kw>=0.78) evaluated all repaired restorations, blindly
      and independently, at baseline and one year. The parameters examined were
      marginal adaptation, anatomic form, surface roughness, marginal discoloration,
      postoperative sensitivity, and secondary caries. The restorations were classified
      as Alpha, Bravo, or Charlie, according to modified US Public Health Service
      criteria. Mann-Whitney and Wilcoxon tests were used to compare the groups.
      RESULTS: Of the 100 restorations repaired in this study, 93 were reexamined at
      baseline. Dropout from baseline to one-year recall was 11%. No statistically
      significant differences were found between the materials for all clinical
      criteria, at baseline or at one-year recall (p>0.05). No statistically
      significant differences were registered (p>0.05) for each material when compared
      for all clinical criteria at baseline and at one-year recall. CONCLUSIONS: The
      hypothesis tested in this randomized controlled clinical trial was accepted.
      After the one-year evaluations, the silorane-based composite exhibited a similar
      performance compared with dimethacrylate-based composite when used to make
      repairs.

PMID- 22616929
TI  - Periapical healing after direct pulp capping with calcium-enriched mixture
      cement: a case report.
AB  - This article describes a successful direct pulp capping of a mature symptomatic
      mandibular second molar in a 14-year-old girl. The patient was referred with
      sensitivity to cold beverages and pain on chewing on the second left mandibular
      molar. Clinical examinations revealed extensive coronal caries and sensitivity to
      percussion. Radiographically, the tooth was mature and had a widened apical
      periodontal ligament (PDL) and a narrow periapical lesion. The concluding
      diagnosis was symptomatic irreversible pulpitis with symptomatic apical
      periodontitis. Treatment included caries removal under rubber dam isolation,
      capping of exposure sites with calcium-enriched mixture (CEM) cement, and
      permanent coronal restoration. At three-, 10-, and 15-month follow-up, the tooth
      was functional, had normal response to cold test, and did not have sensitivity to
      percussion. The PDL space regained its normal width, and the periapical lesion
      healed.

PMID- 22616931
TI  - Phosphorylation of cyclic AMP-response element-binding protein (CREB) is
      influenced by melatonin treatment in pancreatic rat insulinoma beta-cells (INS
      1).
AB  - The pineal hormone melatonin exerts its influence on the insulin secretion of
      pancreatic islets by a variety of signalling pathways. The purpose of the present
      study was to analyse the impact of melatonin on the phosphorylated transcription
      factor cAMP-response element-binding protein (pCREB). In pancreatic rat
      insulinoma beta-cells (INS-1), pCREB immunofluorescence intensities in cell
      nuclei using digitised confocal image analysis were measured to semi-quantify
      differences in the pCREB immunoreactivity (pCREB-ir) caused by different
      treatments. Increasing concentrations of forskolin or 3-isobutyl-1-methylxanthine
      (IBMX) resulted in a dose-dependent rise of the mean fluorescence intensity in
      pCREB-ir nuclear staining. Concomitant melatonin application significantly
      decreased pCREB-ir in INS-1 cells after 30-min, 1-hr and 3-hr treatment. The
      melatonin receptor antagonists luzindole and 4-phenyl-2-propionamidotetraline (4P
      PDOT) completely abolished the pCREB phosphorylation-decreasing effect of
      melatonin, indicating that both melatonin receptor isoforms (MT(1) and MT(2)) are
      involved. In a transfected INS-1 cell line expressing the human MT(2) receptor,
      melatonin caused the greatest reduction in pCREB after IBMX treatment compared
      with nontransfected INS-1 cells, indicating a crucial influence of melatonin
      receptor density on pCREB regulation. Furthermore, the downregulation of pCREB by
      melatonin is concomitantly associated with a statistically significant
      downregulation of Camk2d transcript levels, as measured after 3 hr. In
      conclusion, the present study provides evidence that the phosphorylation level of
      CREB is modulated in pancreatic beta-cells by melatonin. Mediated via CREB,
      melatonin regulates the expression of genes that play an important functional
      role in the regulation of beta-cell signalling pathways.

PMID- 22616932
TI  - Fluorescent penta- and hexaene fatty acids by a Wittig-Horner/elimination
      strategy.
AB  - Molecular fluorescent probes have revolutionized biochemical and biophysical
      studies in the last decades, but with regard to lipids there has been a lack of
      combining the slim shape of saturated acyl chains with fluorescent properties.
      Our strategy to pentaene and hexaene fatty acids builds upon commercially
      available 4-(E)-decenal, which is subjected to a Wittig-Horner reaction after
      chlorination in alpha-position. DBU-mediated beta-elimination of HCl proceeding
      the olefination establishes a highly conjugated system to which a salt-free
      Wittig reaction adds a final double bond leading to a good (Z)-selectivity of 83
      86%. The double bond geometry can be optionally isomerized with I(2) to furnish
      the all-(E)-species. The five conjugated alkene moieties result in a longest
      wavelength absorption maximum of about 350 nm. A red-shift to 380 nm was realized
      by addition of another double bond employing a common Wittig-Horner prolongation
      sequence. Stokes shifts of about 7300 and 7800 cm(-1), respectively, were
      observed.

PMID- 22616933
TI  - Does the light influence astaxanthin production in Xanthophyllomyces dendrorhous?
AB  - Astaxanthin (C40H52O4) is an important natural pigment that has considerable
      promising applications in human health. Until now, many efforts were made aimed
      to develop economically sustainable bioprocesses alternative to the chemical
      synthesis, to satisfy the increasing demand of this ketocarotenoid from feed,
      food and cosmetic industries. The extraction of natural astaxanthin from the
      yeast Xanthophyllomyces dendrorhous till now seems to be rather expensive if
      compared with chemically synthesized astaxanthin. In this article, astaxanthin
      production by Xanthophyllomyces dendrorhous under two different conditions was
      studied: a first effort was made using a conventional reactor while a second
      using an enlightened one. This research was aimed also to optimise astaxanthin
      production by testing the influence of the light and of some nutrient sources.
      From fermentation tests, an astaxanthin yield ranging about 970 ug g(-1) was
      obtained after fed batch cultivation in the conventional reactor. In the
      enlightened reactor lower values, about 930 ug g(-1), were found.

PMID- 22616934
TI  - Production and validation of model iron-tannate dyed textiles for use as historic
      textile substitutes in stabilisation treatment studies.
AB  - BACKGROUND: For millennia, iron-tannate dyes have been used to colour ceremonial
      and domestic objects shades of black, grey, or brown. Surviving iron-tannate dyed
      objects are part of our cultural heritage but their existence is threatened by
      the dye itself which can accelerate oxidation and acid hydrolysis of the
      substrate. This causes many iron-tannate dyed textiles to discolour and decrease
      in tensile strength and flexibility at a faster rate than equivalent undyed
      textiles. The current lack of suitable stabilisation treatments means that many
      historic iron-tannate dyed objects are rapidly crumbling to dust with the
      knowledge and value they hold being lost forever.This paper describes the
      production, characterisation, and validation of model iron-tannate dyed textiles
      as substitutes for historic iron-tannate dyed textiles in the development of
      stabilisation treatments. Spectrophotometry, surface pH, tensile testing, SEM
      EDX, and XRF have been used to characterise the model textiles. RESULTS: On
      application to textiles, the model dyes imparted mid to dark blue-grey
      colouration, an immediate tensile strength loss of the textiles and an increase
      in surface acidity. The dyes introduced significant quantities of iron into the
      textiles which was distributed in the exterior and interior of the cotton, abaca,
      and silk fibres but only in the exterior of the wool fibres. As seen with
      historic iron-tannate dyed objects, the dyed cotton, abaca, and silk textiles
      lost tensile strength faster and more significantly than undyed equivalents
      during accelerated thermal ageing and all of the dyed model textiles, most
      notably the cotton, discoloured more than the undyed equivalents on ageing.
      CONCLUSIONS: The abaca, cotton, and silk model textiles are judged to be suitable
      for use as substitutes for cultural heritage materials in the testing of
      stabilisation treatments.

PMID- 22616935
TI  - Detection and management of nephrotoxicity during drug development.
AB  - INTRODUCTION: The kidneys are vulnerable to injury due to their high filtration
      capacity and high metabolic activity, and most drugs, especially hydrophilic
      drugs and their metabolites, are eliminated largely by kidneys in urine, thus
      increasing the risk of drug-induced nephrotoxicity (DIN). DIN accounts for 18 -
      27% of community- and hospital-acquired episodes of acute kidney injury (AKI) and
      is a serious concern during development of novel therapeutic drugs. AREAS
      COVERED: This review provides an overview of definitions, classification, risk
      factors, complications, and outcomes of DIN. In addition, it gives a practical
      source of information when dealing with nephrotoxicity issues during drug
      development and provides guidance on renal safety risk evaluation for clinical
      studies. Lastly, current research focus in the search for novel biomarkers of DIN
      is also provided. EXPERT OPINION: To enable early detection of DIN and to ensure
      patients' safety through appropriate risk minimization and mitigation strategies,
      future research should focus on identification and validation of novel predictive
      biomarkers of kidney injury and development of DIN-specific classification and
      staging system. This could help in reducing the current high rate of attrition
      during drug development, and reduce marketing and post-marketing withdrawals of
      nephrotoxic drugs.

PMID- 22616936
TI  - Tobacco smoke exposure and allergic sensitization in children: a propensity score
      analysis.
AB  - BACKGROUND AND OBJECTIVE: There is conflicting evidence of the effect of
      environmental tobacco smoke (ETS) on the development of allergic diseases in
      children. Studies have shown that this relationship differs depending on maternal
      history of the disease. We employed the rigour of propensity score methods to
      assess this relationship using data from a birth cohort. METHODS: Using n = 662
      children from the Wayne County Health, Environment, Allergy and Asthma
      Longitudinal Study, we assessed the relationship between early-life ETS and
      subsequent allergic sensitization via a positive skin prick test (SPT+) or at
      least one specific immunoglobulin E (IgE) >= 0.35 (sIgE+) in children aged 2-3
      years. Propensity score estimation followed by full and nearest neighbour
      matching was compared with standard multivariable regression models. RESULTS:
      Among children without a maternal history of allergic disease, ETS was positively
      associated with allergic sensitization in children with an adjusted odds ratio
      (aOR) for SPT+ of 2.32 (95% confidence interval (CI): 1.28-4.22) and the aOR for
      sIgE+ was 2.53 (95% CI: 1.43-4.48). Contrarily, for children with a positive
      maternal history, the aOR for SPT+ and sIgE+ was 0.56 (95% CI: 0.24-1.32) and
      0.43 (95% CI: 0.20-0.91), respectively. CONCLUSIONS: Using propensity score
      methods to rigorously control for confounding factors, ETS exposure was found to
      reduce the risk of allergic sensitization in children with a positive maternal
      history. There is a strong association between early-life ETS and the development
      of allergic sensitization for children aged 2-3 years without maternal history.

PMID- 22616937
TI  - Functional outcome in young adult ischemic stroke: impact of lipoproteins.
AB  - AIM: To determine the functional outcome in a cohort of young adults with
      ischemic stroke patients, focusing on components of lipid profile. METHODS: In
      our registry including consecutive patients with first-ever ischemic stroke aged
      15-49 from 1994 to 2007, we analyzed predictors of 3-month functional outcome
      (modified Rankin Scale, mRS). Infarct size fell into small, medium, large
      posterior, or large anterior. Stroke severity was assessed with NIH Stroke Scale
      (NIHSS). Serum lipids were measured within 72 h after admission. Binary,
      multinomial ordinal, and Poisson regressions allowed revealing factors associated
      with size of infarct, stroke severity, and unfavorable outcome or death (mRS, 2
      6) or mRS as an ordinal measure. RESULTS: In the 968 patients included (mean age,
      41.3 +/- 7.6; 62.6% men; 49.5% with mRS 0-1), factors associated with unfavorable
      outcome after multivariable analysis were increasing age (odds ratio, 1.03 per
      year; 95% confidence interval, 1.01-1.05), higher NIHSS score (1.23 per point,
      1.17-1.29), large anterior (4.37, 2.26-8.42) or posterior (1.73, 1.05-2.85)
      infarcts, bilateral lesions (2.28, 1.30-3.98), internal carotid artery dissection
      (ICAD) (3.65, 1.41-9.47), and inversely high-density lipoprotein (HDL) levels
      (0.58 per unit increase, 0.38-0.86). Increasing HDL associated with smaller
      infarct size (0.71, 0.51-0.98). Both higher total and HDL cholesterol associated
      with lower NIHSS score (0.96, 0.93-0.98 for total cholesterol and 0.82, 0.75-0.88
      for HDL) and lower 3-month mRS (0.87, 0.78-0.97 for total cholesterol and 0.65,
      0.47-0.90 for HDL). CONCLUSION: In addition to known prognosticators, ICAD and
      lower HDL levels were independently associated with adverse clinical outcomes in
      our young adult stroke cohort.

PMID- 22616938
TI  - Construction of semisynthetic DNA-protein conjugates with Phi X174 Gene-A*
      protein.
AB  - DNA-protein conjugates have frequently been used as versatile molecular tools for
      a variety of applications in biotechnology to harness synergistic effects of DNA
      and protein functions. With applications for DNA-protein conjugates growing, easy
      to-use and economical methods for the synthesis of DNA-protein conjugates are
      required. In this study, we developed a method for site-specific labeling of
      single-stranded DNA (ssDNA) to a recombinant protein of interest (POI) through
      the Gene-A* protein (Gene-A*) from bacteriophage phi X174, without any chemical
      modifications of ssDNA. Gene-A* protein is an enzyme that site-selectively
      cleaves an oligodeoxyribonucleotide (ODN) containing a Gene-A* recognition
      sequence, at which point a tyrosine residue of Gene-A* is bonded to the 5'
      phosphoryl group of the cleavage site via a stable phosphotyrosine linkage. Here,
      we constructed three kinds of recombinant proteins fused to Gene-A*: N-terminally
      Gene-A*-fused enhanced green fluorescent protein (EGFP), C-terminally Gene-A*
      fused EGFP, and N-terminally Gene-A*-fused firefly luciferase (FLuc). The
      reaction yields of DNA-protein conjugation catalyzed by the Gene-A* moiety
      reached 80-90% in the three proteins, and kinetic study revealed that the
      reaction achieved a steady state after 10 min. Moreover, dot blot analyses were
      performed to evaluate the hybridization and aptamer-forming ability of ssDNA
      conjugated to the Gene-A* moiety of a recombinant Gene-A*-FLuc protein. This
      study demonstrated that a strategy using recombinant proteins fused to Gene-A*
      could offer a versatile, rapid, easy-to-use, and economical platform for
      producing DNA-protein conjugates. 

PMID- 22616939
TI  - The effect of diabetes on the diagnostic and prognostic performance of mid-region
      pro-atrial natriuretic peptide and mid-region pro-adrenomedullin in patients with
      acute dyspnea.
AB  - Serum mid-regional pro-atrial natriuretic peptide (MR-proANP) and pro
      adrenomedullin (MR-proADM) are novel biomarkers for acute heart failure (AHF).
      Like other AFH biomarkers, the performance of these tests are affected by the
      presence of clinical variables such as renal failure and obesity. In a substudy
      of the Biomarkers from Acute Heart Failure Study, we show that diabetes did not
      influence the performance of these markers with regards to AHF diagnosis or 90
      day all cause death. However, in patients without AHF, increased MR-proADM alone
      was associated with the presence of diabetes.

PMID- 22616940
TI  - Photochemical generation and reactivity of the major hydroxyl radical adduct of
      thymidine.
AB  - 5,6-Dihydro-5-hydroxythymidin-6-yl radical (1), the major reactive intermediate
      resulting from hydroxyl radical addition to C5 of the pyrimidine, is produced via
      350 nm photolysis of a 2,5-dimethoxyphenylsulfide precursor (2). Competition
      between O(2) and thiol for 1 suggests that the radical reacts relatively slowly
      with beta-mercaptoethanol compared to other alkyl radicals. Overall, aryl sulfide
      2 should be an effective precursor for the major hydroxyl radical adduct of
      thymidine in DNA.

PMID- 22616941
TI  - Overrepresentation of transcription factor families in the genesets underlying
      breast cancer subtypes.
AB  - BACKGROUND: The human genome contains a large amount of cis-regulatory DNA
      elements responsible for directing both spatial and temporal gene-expression
      patterns. Previous studies have shown that based on their mRNA expression breast
      tumors could be divided into five subgroups (Luminal A, Luminal B, Basal,
      ErbB2(+) and Normal-like), each with a distinct molecular portrait. Whole genome
      gene expression analysis of independent sets of breast tumors reveals repeatedly
      the robustness of this classification. Furthermore, breast tumors carrying a TP53
      mutation show a distinct gene expression profile, which is in strong association
      to the distinct molecular portraits. The mRNA expression of 552 genes, which
      varied considerably among the different tumors, but little between two samples of
      the same tumor, has been shown to be sufficient to separate these tumor
      subgroups. RESULTS: We analyzed in silico the transcriptional regulation of genes
      defining the subgroups at 3 different levels: 1. We studied the pathways in which
      the genes distinguishing the subgroups of breast cancer may be jointly involved
      including upstream regulators (1st and 2nd level of regulation) as well as
      downstream targets of these genes. 2. Then we analyzed the promoter areas of
      these genes (-500 bp tp +100 bp relative to the transcription start site) for
      canonical transcription binding sites using Genomatix. 3. We looked for the
      actual expression levels of the identified TF and how they correlate with the
      overrepresentation of their TF binding sites in the separate groups. We report
      that promoter composition of the genes that most strongly predict the patient
      subgroups is distinct. The class-predictive genes showed a clearly different
      degree of overrepresentation of transcription factor families in their promoter
      sequences. CONCLUSION: The study suggests that transcription factors responsible
      for the observed expression pattern in breast cancers may lead us to important
      biological pathways.

PMID- 22616942
TI  - Passive sequestration of atmospheric CO2 through coupled plant-mineral reactions
      in urban soils.
AB  - Photosynthetic removal of CO(2) from the atmosphere is an important planetary
      carbon dioxide removal mechanism. Naturally, an amount equivalent to all
      atmospheric carbon passes through the coupled plant-soil system within 7 years.
      Plants cycle up to 40% of photosynthesized carbon through their roots, providing
      a flux of C at depth into the soil system. Root-exuded carboxylic acids have the
      potential to supply 4-5 micromoles C hr(-1)g(-1) fresh weight to the soil
      solution, and enhance silicate mineral weathering. Ultimately, the final product
      of these root-driven processes is CO(2), present in solution as bicarbonate. This
      combines with Ca liberated by corrosion associated with silicate mineral
      weathering to enter the soil-water system and to produce pedogenic calcium
      carbonate precipitates. Combining understanding of photosynthesis and plant root
      physiology with knowledge of mineral weathering provides an opportunity to design
      artificial soils or to plan land use in ways that maximize removal and
      sequestration of atmospheric CO(2) through artificially enhanced pedogenic
      carbonate precipitation. This process requires relatively low energy and
      infrastructure inputs. It offers a sustainable carbon dioxide removal mechanism
      analogous to the use of constructed wetlands for the passive remediation of
      contaminated waters, and is likely to achieve wide public acceptance.

PMID- 22616943
TI  - Effect of current breastfeeding on sleep patterns in infants from Asia-Pacific
      region.
AB  - AIM:   The aim of this study was to assess the relationship between breastfeeding
      and sleep patterns in infants from Asia-Pacific region. METHODS:   Parents of 10
      321 infants (0-11 months) from Australia, China, Hong Kong, India, Indonesia,
      Korea, Japan, Malaysia, New Zealand, the Philippines, Singapore, Taiwan, Thailand
      and Vietnam completed an expanded version of the Brief Infant Sleep
      Questionnaire. RESULTS:   Overall, 4714 (45.72%) were currently being breastfed;
      61.3% of those between 0 and 5 months and 36.6% of those between 6 and 11 months.
      Currently breastfed infants, when compared with not currently breastfed infants,
      had a significant increase in the number and duration of night-time wakings and
      less consolidated sleep. Interestingly, currently breastfed infants less than 6
      months also showed longer duration of daytime sleep and obtained more sleep
      overall. Of note, of those who were currently breastfed, those infants who were
      nursed back to sleep during night, woke up more often at night (2.41 vs. 1.67
      times) and had shorter continuous night-time sleep period (5.58 vs. 6.88 h; P <
      0.001). There was no significant difference between breastfeeding and non
      breastfeeding infants in the number of night wakings, when the nursing to sleep
      variable was controlled for in the analysis of variance. CONCLUSION:  
      Breastfeeding is associated with reduced sleep consolidation in infants. This
      relationship, however, may be moderated by parenting practices of nursing to
      sleep and back to sleep during the night. Thus, parents of infants with night
      waking problems should be encouraged to limit the association between nursing and
      falling to sleep, to improve sleep while maintaining breastfeeding.

PMID- 22616944
TI  - Comparative analysis of beta-carotene hydroxylase genes for astaxanthin
      biosynthesis.
AB  - Astaxanthin (3,3'-dihydroxy-4,4'-diketo-beta-carotene) (1) is a carotenoid of
      significant commercial value due to its superior antioxidant potential,
      application as a component of animal feeds, and ongoing research that links its
      application to the treatment and prevention of human pathologies. The high
      commercial cost of 1 is also based upon its complex synthesis. Chemical synthesis
      has been demonstrated, but produces a mixture of stereoisomers with limited
      applications. Production from biological sources is limited to natural producers
      with complex culture requirements. The biosynthetic pathway for 1 is well
      studied; however, questions remain that prevent optimized production in
      heterologous systems. Presented is a direct comparison of 12 beta-carotene (2)
      hydroxylases derived from archaea, bacteria, cyanobacteria, and plants.
      Expression in Escherichia coli enables a comparison of catalytic activity with
      respect to zeaxanthin (3) and 1 biosynthesis. The most suitable beta-carotene
      hydroxylases were subsequently expressed from an efficient dual expression
      vector, enabling 1 biosynthesis at levels up to 84% of total carotenoids. This
      supports efficient 1 biosynthesis by balanced expression of beta-carotene
      ketolase and beta-carotene hydroxylase genes. Moreover, our work suggests that
      the most efficient route for astaxanthin biosynthesis proceeds by hydroxylation
      of beta-carotene to zeaxanthin, followed by ketolation.

PMID- 22616945
TI  - Experimental and computational investigation of Au25 clusters and CO2: a unique
      interaction and enhanced electrocatalytic activity.
AB  - Atomically precise, inherently charged Au(25) clusters are an exciting prospect
      for promoting catalytically challenging reactions, and we have studied the
      interaction between CO(2) and Au(25). Experimental results indicate a reversible
      Au(25)-CO(2) interaction that produced spectroscopic and electrochemical changes
      similar to those seen with cluster oxidation. Density functional theory (DFT)
      modeling indicates these changes stem from a CO(2)-induced redistribution of
      charge within the cluster. Identification of this spontaneous coupling led to the
      application of Au(25) as a catalyst for the electrochemical reduction of CO(2) in
      aqueous media. Au(25) promoted the CO(2) -> CO reaction within 90 mV of the
      formal potential (thermodynamic limit), representing an approximate 200-300 mV
      improvement over larger Au nanoparticles and bulk Au. Peak CO(2) conversion
      occurred at -1 V (vs RHE) with approximately 100% efficiency and a rate 7-700
      times higher than that for larger Au catalysts and 10-100 times higher than those
      for current state-of-the-art processes.

PMID- 22616946
TI  - Transaortic transcatheter aortic valve implantation: potential issues associated
      with the use of the ASCENDRA transapical delivery system.
AB  - Transaortic transcatheter aortic valve implantation (TAo-TAVI) has been recently
      proposed as an alternative to transapical (TA) and transfemoral (TF) approach. We
      now discuss a technical issue associated with TAo-TAVI related to the use of a
      delivery system dedicated to the antegrade TA approach. The potential solutions
      to this issue as well as the potential advantages of the TAo approach are
      discussed.

PMID- 22616947
TI  - Plasma sRAGE enables prediction of acute lung injury after cardiac surgery in
      children.
AB  - INTRODUCTION: Acute lung injury (ALI) after cardiac surgery is associated with a
      high postoperative morbidity and mortality, but few predictors are known for the
      occurrence of the complication. This study evaluated whether elevated plasma
      levels of soluble receptor for advanced glycation end products (sRAGE) and
      S100A12 reflected impaired lung function in infants and young children after
      cardiac surgery necessitating cardiopulmonary bypass (CPB). METHODS: Consecutive
      children younger than 3 years after cardiac surgery were prospectively enrolled
      and assigned to ALI and non-ALI groups, according to the American-European
      Consensus Criteria. Plasma concentrations of sRAGE and S100A12 were measured at
      baseline, before, and immediately after CPB, as well as 1 hour, 12 hours, and 24
      hours after operation. RESULTS: Fifty-eight patients were enrolled and 16 (27.6%)
      developed postoperative ALI. Plasma sRAGE and S100A12 levels increased
      immediately after CPB and remained significantly higher in the ALI group even 24
      hour after operation (P < 0.01). In addition, a one-way MANOVA revealed that the
      overall sRAGE and S100A12 levels were higher in the ALI group than in the non-ALI
      group immediately after CPB (P < 0.001). The multivariate logistic regression
      analysis showed that the plasma sRAGE level immediately after CPB was an
      independent predictor for postoperative ALI (OR, 1.088; 95% CI, 1.011 to 1.171; P
      = 0.025). Increased sRAGE and S100A12 levels immediately after CPB were
      significantly correlated with a lower PaO2/FiO2 ratio (P < 0.01) and higher
      radiographic lung-injury score (P < 0.01), as well as longer mechanical
      ventilation time (sRAGEN: r = 0.405; P = 0.002; S100A12N: r = 0.322; P = 0.014),
      longer surgical intensive care unit stay (sRAGEN: r = 0.421; P = 0.001; S100A12N:
      r = 0.365; P = 0.005) and hospital stay (sRAGEN: r = 0.329; P = 0.012; S100A12N:
      r = 0.471; P = 0.001). CONCLUSIONS: Elevated sRAGE and S100A12 levels correlate
      with impaired lung function, and sRAGE is a useful early biomarker of ALI in
      infants and young children undergoing cardiac surgery.

PMID- 22616948
TI  - Thiazolidinedione safety.
AB  - INTRODUCTION: Thiazolidinediones (TZDs) initially showed great promise as unique
      receptor-mediated oral therapy for type 2 diabetes, but a host of serious side
      effects, primarily cardiovascular, have limited their utility. It is crucial at
      this point to perform a risk-benefit analysis to determine what role TZDs should
      play in our current treatment of type 2 diabetes and where the future of this
      class of drugs is headed. AREAS COVERED: This review provides a comprehensive
      overview of the literature from 2000 onward reporting the known side effects of
      rosiglitazone and pioglitazone, with commentary on the quality of the data
      available, putative mechanism of each side effect and clinical significance.
      Finally, a perspective on the future of the TZDs as a class is provided. EXPERT
      OPINION: The current TZDs are first-generation, non-specific activators of
      peroxisome proliferator-activated receptor (PPAR) gamma, resulting in a wide
      array of deleterious side effects that currently limit their use. However, the
      development of highly targeted selective PPAR gamma modulators (SPPARgammaMs) and
      dual PPAR gamma/alpha agonists is on the horizon.

PMID- 22616949
TI  - Mass Spectrometric and Synchrotron Radiation based techniques for the
      identification and distribution of painting materials in samples from paints of
      Josep Maria Sert.
AB  - BACKGROUND: Establishing the distribution of materials in paintings and that of
      their degradation products by imaging techniques is fundamental to understand the
      painting technique and can improve our knowledge on the conservation status of
      the painting. The combined use of chromatographic-mass spectrometric techniques,
      such as GC/MS or Py/GC/MS, and the chemical mapping of functional groups by
      imaging SR FTIR in transmission mode on thin sections and SR XRD line scans will
      be presented as a suitable approach to have a detailed characterisation of the
      materials in a paint sample, assuring their localisation in the sample build-up.
      This analytical approach has been used to study samples from Catalan paintings by
      Josep Maria Sert y Badia (20th century), a muralist achieving international
      recognition whose canvases adorned international buildings. RESULTS: The pigments
      used by the painter as well as the organic materials used as binders and
      varnishes could be identified by means of conventional techniques. The
      distribution of these materials by means of Synchrotron Radiation based
      techniques allowed to establish the mixtures used by the painter depending on the
      purpose. CONCLUSIONS: Results show the suitability of the combined use of SR
      MUFTIR and SR MUXRD mapping and conventional techniques to unequivocally identify
      all the materials present in the sample and their localization in the sample
      build-up. This kind of approach becomes indispensable to solve the challenge of
      micro heterogeneous samples. The complementary interpretation of the data
      obtained with all the different techniques allowed the characterization of both
      organic and inorganic materials in the samples layer by layer as well as to
      establish the painting techniques used by Sert in the works-of-art under study.

PMID- 22616950
TI  - Simultaneous enhancement of cell proliferation and thermally induced harvest
      efficiency based on temperature-responsive cationic copolymer-grafted
      microcarriers.
AB  - The development of large-scale suspension cell cultures using microcarriers has
      long been a focus of attention in the fields of pharmacy and biotechnology.
      Previously, we developed cell-detachable microcarriers based on temperature
      responsive poly(N-isopropylacrylamide) (PIPAAm)-grafted beads, on which adhering
      cells can be noninvasively harvested by only reducing the temperature without the
      need for proteolytic enzyme treatment. In this study, to improve the cell harvest
      efficiency from bead surfaces while maintaining cell adhesion and proliferation
      properties, we prepared temperature-responsive cationic copolymer-grafted beads
      bearing a copolymer brush consisting of IPAAm, positively charged quaternary
      amine monomer (3-acrylamidopropyl trimethylammonium chloride; APTAC), and
      hydrophobic monomer (N-tert-butylacrylamide; tBAAm). The incorporation of
      positively charged APTAC into the grafted copolymer brush facilitated bead
      dispersibility in a cell culture system containing Chinese hamster ovary (CHO-K1)
      cells and consequently allowed for enhanced cell proliferation in the system
      compared to that of unmodified CMPS and conventional PIPAAm homopolymer-grafted
      beads. Additionally, P(IPAAm-co-APTAC-co-tBAAm) terpolymer-grafted beads
      exhibited the most rapid and efficient cell detachment behavior after the
      temperature was reduced to 20  degrees C, presumably because the highly hydrated
      APTAC promoted the overall hydration of the P(IPAAm-co-APTAC-co-tBAAm) chains.
      Therefore, P(IPAAm-co-APTAC-co-tBAAm) terpolymer-grafted microcarriers are
      effective in facilitating both cell proliferation and thermally induced cell
      detachment in a suspension culture system.

PMID- 22616951
TI  - Health-related quality of life supersedes other psychosocial predictors of long
      term survival in cancer patients undergoing radiotherapy.
AB  - BACKGROUND: To investigate the prognostic value of several psychosocial factors
      for long-term survival in cancer patients. MATERIAL AND METHODS: Baseline data
      were gathered in routine radiotherapy practice during 44 months. The analysis is
      based on 938 patients for whom follow-up data were available. Baseline
      psychosocial distress, depression, health-related quality of life (HRQOL), and
      life satisfaction were assessed using Questionnaire on Stress in Cancer Patients
      (QSC-R23), Self-Rating Depression Scale (SDS), Functional Assessment of Therapy -
      General (FACT-G) questionnaire, and Questions on Life Satisfaction (FLZ(M)).
      Patients were followed up for 7 to 10 years. Kaplan-Meier plots and Cox
      proportional hazards models were used to investigate associations between
      sociodemographic, clinical, psychosocial factors and overall survival (OS).
      RESULTS: Patients' median survival time was 35 months (95% CI 28.9-41.1).
      Significant multivariate predictors of OS were age, health insurance type,
      Karnofsky performance status, cancer site, and cancer stage. Controlling for
      these variables, HRQOL was the only psychosocial predictor of survival (hazard
      ratio 0.988, 95% CI 0.979-0.997, p =0.009). The physical well-being and the
      functional well-being subscales of the FACT-G emerged as the relevant HRQOL
      facets predictive of survival. CONCLUSION: HRQOL has incremental predictive value
      for long-term survival in cancer patients.

PMID- 22616952
TI  - The role of informal caregivers during cancer patients' recovery from
      chemotherapy.
AB  - AIMS: (i) To investigate the availability, perceived importance and roles of
      informal caregivers in the recovery of patients treated at day oncology centres
      and (ii) identify differences between patients with and without informal
      caregivers in the extent to which they experienced symptoms, and the level of
      bother symptoms caused. METHOD: Patients from three Australian hospitals (n =
      122) were recruited during cycles 1 or 2 of adjuvant chemotherapy. Participants
      completed a modified version of the Rotterdam Symptom Checklist (RSCL) each day
      for 5 days after chemotherapy. A telephone interview conducted 10 days post
      treatment explored the availability, importance and roles of caregivers. During
      the interview, participants also completed the modified RSCL in which they were
      asked about the extent to which they experienced, and were bothered by, each
      symptom over the prior 5 days combined. RESULTS: Overall, 71% of participants had
      an informal caregiver in the 5 days postchemotherapy, commonly a partner. More
      women (71%) than men (48%) had a caregiver (p < 0.05). Caregivers were perceived
      to be highly important; they were more important for women than men (U = 213.50,
      p < 0.01). The most common assistance caregivers provided was meal preparation
      and emotional support and companionship. On days 6-10 postchemotherapy, the
      extent to which overall physical symptoms were experienced was higher for
      patients with a caregiver than without (U = 987.50, p < 0.05); similarly their
      symptoms caused more bother (U = 966.00, p < 0.01). CONCLUSIONS: These findings
      highlighted the importance of informal caregivers to patients postchemotherapy.
      It is imperative that patients are informed of the importance of this support so
      a caregiver can be arranged, if possible. Understanding the needs of patients
      following chemotherapy would enable health professionals to advise patients, with
      or without caregivers, how to best prepare for and manage their recovery at home.

PMID- 22616953
TI  - Fragrant volatile oil composition of Nutmeg Geranium (Pelargonium * fragrans
      Willd.) from India.
AB  - Hydrodistilled essential oil of 'Nutmeg Geranium' (Pelargonium * fragrans
      Willd.), grown in foothills of northern India was analysed by capillary gas
      chromatography (GC/flame ionisation detector (FID)) and GC-mass spectrometry
      (GC/MS). A total of 51 constituents, representing 90.2% of the total oil
      composition were identified. The oil was mainly dominated by monoterpenoids
      (58.4%), followed by sesquiterpenoids (19.4%), and phenyl propanoids (10.1%).
      Major constituents of the essential oil were fenchone (10.7%), methyl eugenol
      (9.9%), alpha-pinene (9.4%), alpha-thujene (7.6%), limonene (6.4%), spathulenol
      (4.7%), sabinene (4.3%), linalool (4.2%), (E)-caryophyllene (4.2%), terpinen-4-ol
      (3.2%), beta-pinene (2.9%), caryophyllene oxide (2.2%) and bicyclogermacrene
      (2.1%). This is the first report on essential oil composition of Nutmeg Geranium
      oil grown in India.

PMID- 22616954
TI  - Preoperative 6-min walking distance does not predict pulmonary complications in
      upper abdominal surgery.
AB  - BACKGROUND AND OBJECTIVE: Field exercise tests have been increasingly used for
      pulmonary risk assessment. The 6-min walking distance (6MWD) is a field test
      commonly employed in clinical practice; however, there is limited evidence
      supporting its use as a risk assessment method in abdominal surgery. The aim was
      to assess if the 6MWD can predict the development of post-operative pulmonary
      complications (PPCs) in patients having upper abdominal surgery (UAS). METHODS:
      This prospective cohort study included 137 consecutive subjects undergoing
      elective UAS. Subjects performed the 6MWD on the day prior to surgery, and their
      performance were compared with predicted values of 6MWD (p6MWD) using a
      previously validated formula. PPCs (including pneumonia, tracheobronchitis,
      atelectasis with clinical repercussions, bronchospasm and acute respiratory
      failure) were assessed daily by a pulmonologist blinded to the 6MWD results. 6MWD
      and p6MWD were compared between subjects who developed PPC (PPC group) and those
      who did not (no PPC group) using Student's t-test. RESULTS: Ten subjects
      experienced PPC (7.2%) and no significant difference was observed between the
      6MWD obtained in the PPC group and no PPC group (466.0 +/- 97.0 m vs. 485.3 +/-
      107.1 m; P = 0.57, respectively). There was also no significant difference
      observed between groups for the p6MWD (100.7 +/- 29.1% vs. 90.6 +/- 20.9%; P >
      0.05). CONCLUSIONS: The results of the present study suggest that the 6-min
      walking test is not a useful tool to identify subjects with increased risk of
      developing PPC following UAS.

PMID- 22616955
TI  - Formyloxyl radical-gold nanoparticle binding: a theoretical study.
AB  - The citrate reduction method is one of the simplest and most common methods used
      in the synthesis of gold nanoparticles. It has been thought that citrate acts as
      both a reducing agent for the gold salt and as the capping agent. However, it has
      recently been reported using density functional theory (DFT) that electron
      density builds up on uncomplexed apex gold atoms and the binding of formate (the
      simplest carboxylate and a model for citrate) becomes unfavorable after two
      additions, limiting citrate's utility as a capping agent. In this study, Au(20)
      formyloxyl radical interactions are investigated using DFT at the BP86/DZ level
      of theory to model neutral carboxylate-gold nanoparticle binding (corresponding
      to carboxylates interacting with a partially oxidized gold nanoparticle). Binding
      energies are refined using a TZP basis set. It is found that the incremental
      binding energies of formyloxyl radicals remain highly favorable through eight
      additions (the highest number tested). The addition of one formyloxyl radical is
      56 kJ/mol less than the addition of one formate but becomes 210 kJ/mol more
      favorable for the second addition. The range of binding energies through the
      eight additions is 154-331 kJ/mol. Furthermore, after the third addition, the
      most favorable geometries feature distortion of the gold tetrahedron. These
      results suggest that oxidized species formed in the citrate reduction method are
      likely capping agents and that binding of these ligands may affect the properties
      of the nanoparticles through distortion of the gold structure.

PMID- 22616956
TI  - Dropping out of psychiatric treatment: a methodological contribution.
AB  - OBJECTIVE: Treatment interruption rate among psychiatric patients varies from 26%
      to 82%. In order to evaluate the determinants of compliance and dropping out in
      out-patient psychiatric clinics, we utilized Ajzen's theory of planned behaviour.
      METHOD: In the pilot stage (n = 164), a questionnaire was administered to elicit
      the patient's salient beliefs associated with the intention to contact the
      service. In the main stage, a new, broader sample (n = 239) was asked to fill in
      a structured questionnaire including the basic components of the Ajzen's theory;
      a structural equation model was used for the evaluation of the fit between the
      relationships hypothesized by the theory and the empirical data gathered from the
      sample. RESULTS: The most important predictor of 'intention' is 'perceived
      behavioural control', followed by 'attitude'. It was found that 'past behaviour'
      vs. 'intentions' was significant predictor of dropping out. CONCLUSION: Dropout
      patients were more likely to have already been in psychiatric treatment and to
      have had a past history of missed appointments. Our results suggest that knowing
      previous treatment history and the role of interruptions could equip mental
      health carers for the rapid retrieval of dropouts, reducing the burden on
      patients' families and the risk of patients themselves.

PMID- 22616957
TI  - Natural products as sources for new pesticides.
AB  - Natural products as pesticides have been reviewed from several perspectives in
      the past, but no prior treatment has examined the impact of natural product and
      natural product-based pesticides on the U.S. market, as a function of new active
      ingredient registrations with the Environmental Protection Agency (EPA). Thus,
      EPA registration details of new active ingredients for all conventional pesticide
      registrations and biopesticide registrations were compiled from the years 1997
      2010. Conventional pesticide registrations and biopesticide registrations were
      examined both collectively and independently for all 277 new active ingredients
      (NAI) and subsequently categorized and sorted into four types: biological (B),
      natural product (NP), synthetic (S), and synthetic natural derived (SND). When
      examining conventional pesticides alone, the S category accounted for the
      majority of NAI registrations, with 78.0%, followed by SND with 14.7%, NP with
      6.4%, and B with 0.9%. Biopesticides alone were dominated by NPs with 54.8%,
      followed by B with 44.6%, SND with 0.6%, and 0% for S. When examining
      conventional pesticides and biopesticides combined, NPs accounted for the
      majority of NAI registrations, with 35.7%, followed by S with 30.7%, B with
      27.4%, and SND with 6.1%. Despite the common perception that natural products may
      not be the best sources for NAI as pesticides, when both conventional and
      biopesticides are examined collectively, and considering that NP, SND, and B all
      have origins from natural product research, it can be argued that their combined
      impact with the EPA from 1997 to 2010 accounted for 69.3% of all NAI
      registrations.

PMID- 22616958
TI  - Myopathic causes of exercise intolerance with rhabdomyolysis.
AB  - We review the muscular dystrophies and metabolic myopathies associated with
      myalgia and rhabdomyolysis together with some less well-recognized associations
      based upon the personal practice of the authors. A careful history and clinical
      examination will direct investigation towards an accurate molecular diagnosis.
      Non-specific exercise-induced myalgia in the presence of muscle hypertrophy and a
      high creatine kinase will point towards a muscular dystrophy. Symptoms occurring
      within minutes of exercise and with isometric contraction, especially with a
      history of a 'second wind' phenomenon, suggest a disorder of glycogen metabolism.
      In those patients in whom symptoms occur after prolonged exercise, infections,
      fasting, stress, and cold, a disorder of fatty acid oxidation should be
      considered. Heat-induced rhabdomyolysis caused by exercising in hot and humid
      climates should lead the clinician to suspect a mutation in RYR1. Serum creatine
      kinase level should be a checked in all children presenting with leg pains. A
      careful history and examination and laboratory confirmation of myoglobinuria will
      target investigations leading to a correct molecular diagnosis.

PMID- 22616959
TI  - Iron chelation therapy in myelodysplastic syndromes: we need more evidence, not
      more guidelines.

PMID- 22616960
TI  - Stroke management: updated recommendations for treatment along the care
      continuum.
AB  - The Australian Clinical Guidelines for Stroke Management 2010 represents an
      update of the Clinical Guidelines for Stroke Rehabilitation and Recovery (2005)
      and the Clinical Guidelines for Acute Stroke Management (2007). For the first
      time, they cover the whole spectrum of stroke, from public awareness and
      prehospital response to stroke unit and stroke management strategies, acute
      treatment, secondary prevention, rehabilitation and community care. The
      guidelines also include recommendations on transient ischaemic attack. The most
      significant changes to previous guideline recommendations include the extension
      of the stroke thrombolysis window from 3 to 4.5 h and the change from positive to
      negative recommendations for the use of thigh-length antithrombotic stockings for
      deep venous thrombosis prevention and the routine use of prolonged positioning
      for contracture management.

PMID- 22616961
TI  - Unintended consequences of performance measurement in healthcare: 20 salutary
      lessons from the English National Health Service.
AB  - The objective of the study is to review the evidence on the consequences
      associated with the introduction of national performance measurement systems in
      the National Health Service (NHS), with the aim of informing the development of
      similar national performance measurement programmes proposed for Australia.
      Narrative review of the published evidence on the unintended and adverse
      consequences of performance measurement systems in the NHS is the data source. We
      identified 20 different dysfunctional consequences of national performance
      measurement systems in the NHS in four headings. These are poor measurement
      (measurement fixation, tunnel vision, myopia, ossification, anachronism and
      quantification privileging), misplaced incentives and sanctions (complacency,
      silo-creation, overcompensation, undercompensation, insensitivity and increased
      inequality), breach of trust (misrepresentation, gaming, misinterpretation,
      bullying, erosion of trust and reduced staff morale), and politicisation of
      performance systems (political grandstanding and creating a diversion).
      Performance measurement programmes can contribute to systems improvement,
      delivering benefits to health services and patients, as evidenced by the dramatic
      reduction in waiting times in the NHS following the incorporation of targets and
      indicators for waiting times. Nevertheless, experience from the NHS shows that in
      addition to generating desired improvements, performance measures can induce a
      range of unintended and dysfunctional consequences. We recommend Australia to
      heed the lessons of the NHS, and strive to balance effective performance
      measurement and management against the potential drawbacks and adverse
      consequences. Any national performance measures need to be piloted and carefully
      evaluated to assess potential benefits and pitfalls.

PMID- 22616962
TI  - Medicine, art and the death of Franz Liszt.
AB  - Much might be learned about the art of medicine by studying the lives of great
      artists. The year 2011 marked the bicentenary of the birth of Franz Liszt (1811
      1886), one of the most accomplished musicians of the 19th century. Lessons
      relevant to contemporary medical practice can be found by examining aspects of
      his life and art, as well as the failure of his physicians to practise their own
      art during his final days.

PMID- 22616963
TI  - Relationship between body composition, peripheral muscle strength and functional
      exercise capacity in patients with severe chronic obstructive pulmonary disease.
AB  - The influence of body composition and peripheral muscle strength on 6-minute walk
      distance was assessed by performing dual energy X-ray absorptiometry scanning,
      spirometry and dynamometry testing in 13 men and 13 women with severe chronic
      obstructive pulmonary disease. Multivariate modelling showed that 76% of the
      variance in 6-minute walk distance could be explained by an equation
      incorporating lung function, quadriceps strength and lean leg mass. These
      findings indicate an important role for lower limb strength measures in pulmonary
      rehabilitation training programmes.

PMID- 22616965
TI  - Progression of antiphospholipid antibody syndrome to catastrophic
      antiphospholipid antibody syndrome acutely with cessation of antithrombotic
      therapy.
AB  - Catastrophic antiphospholipid antibody syndrome (CAPS) is a serious condition
      that is often unrecognised with a high mortality. Cessation of anticoagulation in
      antiphospholipid antibody syndrome (APS) can have devastating consequences with
      progression to CAPS. Making a diagnosis of APS can however be challenging because
      of the evolving diagnostic criteria and difficulty in confirming thromboses.
      Management of these patients can also be complex, especially in those with
      coexistent thrombocytopenia. New potential treatments are emerging targeted on
      the immunomodulation of APS rather than just prevention of thrombosis. This
      article aims to highlight these diagnostic and management difficulties by
      reporting and discussing three cases of APS with progression to CAPS following
      cessation of anticoagulation, one with fatal consequences, with confirmation of
      CAPS on autopsy, and two with successful treatment and outcomes.

PMID- 22616964
TI  - Utility of atrial temporary pacing as an acute treatment for bradyarrhythmias and
      tachyarrhythmias in the intensive care setting with preservation of
      atrioventricular synchrony.
AB  - Temporary pacing is often used as an acute treatment of bradyarrhythmias and
      suppression of tachyarrhythmias. In patients with cardiogenic shock, loss of
      atrioventricular synchrony may worsen cardiovascular haemodynamics. We present a
      series where temporary right atrial pacing was used as an acute treatment for
      both bradyarrhythmias and tachyarrhythmias.

PMID- 22616966
TI  - Proton pump inhibitors and diarrhoea related to Clostridium difficile infection
      in hospitalised patients: a case-control study.
AB  - The incidence and disease severity of Clostridium difficile infection are rising.
      There is increasing evidence of a potential association between proton-pump
      inhibitors (PPI) and C. difficile infection. We performed a case-control study to
      examine the relationship between PPI and polymerase chain reaction (PCR)-proven
      C. difficile infection in 137 hospitalised patients in a tertiary hospital in
      Western Australia. Only antibiotic exposure within 3 months prior to onset of
      diarrhoea was associated with PCR-proven C. difficile infection (odds ratio 5.97,
      95% confidence interval 2.40-14.8, P= 0.001). A restricted analysis on those who
      had exposure to antibiotics within 3 months before the onset of diarrhoea did not
      change the negative association between PPI exposure and PCR-proven C. difficile
      infection. Long-term PPI usage and intensity of PPI exposure prior to onset of
      diarrhoea were not significantly associated with C. difficile infection.

PMID- 22616967
TI  - Transient acute tetraparesis revealing bihemispheric cerebral infarcts.

PMID- 22616968
TI  - Encrusted cystitis and pyelitis.

PMID- 22616969
TI  - Obliterative bronchiolitis after rituximab administration: a new manifestation of
      rituximab-associated pulmonary toxicity.

PMID- 22616970
TI  - A case of portopulmonary hypertension spanning 18 years: successful use of
      bosentan for progressive disease after two liver transplantations.

PMID- 22616971
TI  - Vitamin B12 deficiency causing hyperhomocysteinaemia and cerebral venous sinus
      thrombosis.

PMID- 22616972
TI  - Viscoelastic and photoresponsive properties of microparticle/liquid-crystal
      composite gels: tunable mechanical strength along with rapid-recovery nature and
      photochemical surface healing using an azobenzene dopant.
AB  - We investigated viscoelastic and photoresponsive properties of the
      microparticle/liquid-crystal (LC) composite gels. The mechanical strength of the
      colloidal gels can be widely tuned by varying particle concentrations. With
      increasing particle concentration, a storage modulus of the particle/LC composite
      gels increased and reached over 10(4) Pa, showing good self-supporting ability.
      We demonstrated for the first time that the particle/LC composite gels exhibited
      rapid and repetitive recovery of the mechanical strength after large-amplitude
      oscillatory breakdown. In addition, photoresponsive properties of the composite
      gels were investigated by the cis-trans photoisomerization of the azobenzene
      compound doped into the host LCs. The photochemical gel-sol transition could be
      repeatedly induced by changing the phase structure of the host LCs between
      nematic and isotropic, using the photoisomerization. The particle/LC composite
      gels can be applied to optically healable materials by the site-selective gel-sol
      transition based on the photochemical modulation of the phase structures of the
      host LCs.

PMID- 22616973
TI  - In memoriam: Lynn Margulis (1938-2011).

PMID- 22616974
TI  - Lifetime of the unpaired electron species in calf thymus DNA thin films induced
      by nitrogen and oxygen K-shell photoabsorption.
AB  - PURPOSE: To study the lifetime of the short-lived unpaired electron species
      induced in a calf thymus DNA film by soft X-rays in the energy regions around
      nitrogen and oxygen K-edge. MATERIALS AND METHODS: Dry calf thymus DNA films were
      measured by electron paramagnetic resonance (EPR) spectrometer during the
      monochromatic soft X-ray irradiation provided from a synchrotron accelerator
      (SPring-8, Super Photon ring-8 GeV). Two operation modes of SPring-8 with
      different electron bunch structures were used to explore dependence of EPR
      intensity on pulse interval of soft X-rays. RESULTS: Observed EPR spectra did not
      show significant difference, in the spectral shape, intensity, g-factor and
      photon energy dependence, between the two bunch modes. CONCLUSIONS: The total
      yield of the unpaired electron species were estimated by assuming the exponential
      relaxation of the unpaired electrons with two different bunch modes of the
      synchrotron. The lifetime of the unpaired electron species is estimated to be in
      the range of a few tens to several hundreds of MUs.

PMID- 22616975
TI  - The standard partial molar volumes of ions in solution. Part 5. Ionic volumes in
      water at 125-200  degrees C.
AB  - The standard partial molar volumes, V(infinity)(i,T), of 12 univalent ions
      (alkali metal, ammonium, halide, nitrate, and perchlorate) and five divalent ions
      (alkaline earth and sulfate) in water at 125, 150, 175, and 200  degrees C and at
      2 MPa were derived from the data of Ellis. Similar data for NH(4)(+) and NO(3)(-)
      at 0-100  degrees C, not included in Part 4, were added, derived from his data
      too. The (negative) electrostrictive volumes, DeltaV(elstr)(i,T), of these ions
      at infinite dilution were obtained from the shell-by-shell calculation of the
      electrostriction according to Marcus and Hefter that takes into account the
      mutual dependence of the relative permittivity of the water around the ion and
      the electrical field strength at it. The expanded volumes of the ions, defined as
      V(Expan)(i,T) = V(infinity)(i,T) - DeltaV(elstr)(i,T), were then derived and
      compared with their intrinsic volumes, calculated according to Glueckauf. The
      calculation yields also the spatial extension of the dielectrically saturated
      region around the ions. The numbers of water molecules, the molar volume of which
      is affected by the ions at infinite dilution, were estimated from the ratio of
      DeltaV(elstr)(i,T) and V(Wel)(T), the latter being the average molar
      electrostriction of the water in the vicinity of the ions.

PMID- 22616976
TI  - Syncope as an initial manifestation of atypical lipomatous hypertrophy of the
      interatrial septum.
AB  - Lipomatous hypertrophy of the interatrial septum (LHIS) is an incidental
      echocardiographic abnormality characterized by dumb-bell configuration of the
      interatrial septum from excess fat deposition. We report a case of syncope in a
      patient with LHIS obstructing the superior vena cava at the right atrial
      junction.

PMID- 22616977
TI  - Effects of trehalose polycation end-group functionalization on plasmid DNA uptake
      and transfection.
AB  - In this study, we have synthesized six analogs of a trehalose
      pentaethylenehexamine glycopolymer (Tr4) that contain (1A) adamantane, (1B)
      carboxy, (1C) alkynyl-oligoethyleneamine, (1D) azido trehalose, (1E) octyl, or
      (1F) oligoethyleneamine end groups and evaluated the effects of polymer end group
      chemistry on the ability of these systems to bind, compact, and deliver pDNA to
      cultured HeLa cells. The polymers were synthesized in one-pot azide-alkyne
      cycloaddition reactions with an adaptation of the Carothers equation for step
      growth polymerization to produce a series of polymers with similar degrees of
      polymerization. An excess of end-capping monomer was added at the end of the
      polymerizations to maximize functionalization efficiency, which was evaluated
      with GPC, NMR, and MALDI-TOF. The polymers were all found to bind and compact
      pDNA at similarly low N/P ratios and form polyplexes with plasmid DNA. The
      effects of the different end group structures were most evident in the polyplex
      internalization and transfection assays in the presence of serum as determined by
      flow cytometry and luciferase gene expression, respectively. The Tr4 polymers end
      capped with carboxyl groups (1B) (N/P = 7), octyne (1E) (N/P = 7), and
      oligoethyleneamine (1F) (N/P = 7), were taken into cells as polyplex and
      exhibited the highest levels of fluorescence, resulting from labeled plasmid.
      Similarly, the polymers end-functionalized with carboxyl groups (1E at N/P = 7),
      octyl groups (1E at N/P = 15), and in particular oligoethyleneamine groups (1F at
      N/P = 15) yielded dramatically higher reporter gene expression in the presence of
      serum. This study yields insight into how very subtle structural changes in
      polymer chemistry, such as end groups can yield very significant differences in
      the biological delivery efficiency and transgene expression of polymers used for
      pDNA delivery.

PMID- 22616978
TI  - Advanced oxidation protein products as prognostic biomarkers for recovery from
      acute kidney injury after coronary artery bypass grafting.
AB  - Recovery from acute kidney injury (AKI) is related to long-term prognosis. This
      study, involving 56 patients with AKI and 56 controls from a prospective cohort
      undergoing coronary artery bypass grafting (CABG), investigated the prognostic
      performance of serum levels of advanced oxidation protein products (AOPPs) for
      predicting non-recovered AKI and non-completely recovered AKI. AOPP levels
      increased significantly 7 days after surgery in patients with non-recovered or
      non-completely recovered AKI. Increased AOPP levels were associated with both
      types of poor recovery from AKI. Results from receiver-operating characteristic
      (ROC) curves demonstrated that AOPP levels had good prognostic value for
      predicting non-recovered and non-completely recovered AKI.

PMID- 22616979
TI  - A general, enantioselective synthesis of protected morpholines and piperazines.
AB  - A short, high yielding protocol has been developed for the enantioselective and
      general synthesis of C2-functionalized, benzyl protected morpholines and
      orthogonally N,N'-protected piperazines from a common intermediate.

PMID- 22616980
TI  - Early versus late amniotomy for labour induction: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the impact of early vs. late amniotomy on delivery mode in
      women undergoing induction of labor. STUDY DESIGN: 143 women admitted for
      induction were randomized to early amniotomy (EA, concomitant with the beginning
      of oxytocin infusion; n = 71) or to late amniotomy (LA, four hours after the
      beginning of oxytocin; n = 72). Randomization was stratified by parity. The
      primary outcome was the rate of cesarean. Secondary outcomes were duration of
      labor and intrapartum fever. RESULTS: The cesarean rate was similar between
      groups (18% vs. 17% among nulliparous; and 3% vs. 0% among parous women, in EA
      and LA group, respectively). However, EA was associated with shorter oxytocin-to
      delivery interval (12 vs. 15 h) and a non-significant decrease in intrapartum
      fever (3% vs. 25%) than LA in nulliparous women (p = 0.05). CONCLUSION: For women
      undergoing oxytocin induction, early amniotomy is associated with shorter labor
      in nulliparous women with no effect on the risk of cesarean section in both
      nulliparous and multiparous women.

PMID- 22616981
TI  - The safety and efficacy of antitumour necrosis factor-alpha therapy for
      inflammatory bowel disease in patients post liver transplantation: a case series.
AB  - BACKGROUND: The role of antitumour necrosis factor-alpha (anti-TNF) therapy for
      inflammatory bowel disease (IBD) among liver transplant recipients is largely
      unknown given the rarity of this population and the paucity of literature on the
      subject. AIM: To investigate the safety and efficacy of anti-TNF therapy for
      refractory IBD in the post liver transplant population. METHODS: The liver
      transplant database at London Health Sciences Centre was searched to identify
      adult patients with IBD treated with anti-TNF therapy post transplantation.
      RESULTS: Six patients (five men, one woman) were identified, aged 28-65. All
      patients had cadaveric orthotopic liver transplants. Four patients required
      transplantation due to primary sclerosing cholangitis, one due to autoimmune
      hepatitis, and one due to biliary atresia. Five patients suffered from Crohn's
      disease and the remaining patient from indeterminate colitis. All patients were
      treated with infliximab 5 mg/kg every 8 weeks after undergoing induction at weeks
      0, 2 and 6, with the exception of one patient. The duration of infliximab therapy
      ranged from 8 weeks to 4 years. Four patients treated with infliximab experienced
      sustained improvement of their IBD symptoms post transplantation, as documented
      by Harvey-Bradshaw Index scores demonstrating clinical remission. Of the
      remaining two patients, neither had sustained improvement of their IBD with
      infliximab or subsequent adalimumab. One patient was diagnosed with systemic
      lupus erythematosus and another with colorectal adenocarcinoma following anti-TNF
      therapy. Otherwise, no side effects were attributed to anti-TNF therapy.
      CONCLUSIONS: Based on this case series, anti-TNF therapy appears to be safe and
      effective for treating refractory IBD in patients post liver transplantation.
      These patients respond to anti-TNF therapy similar to those who have not been
      previously transplanted.

PMID- 22616983
TI  - Governing couple-sexuality: publically funded couples' courses in Norway.
AB  - This paper analyses the construction of Norwegian couples' sexuality through the
      study of a publically financed and organised relationship course called Living
      Well Together (Godt Samliv). Established in 2005, this relationship course aimed
      at first-time parent couples is offered free of charge by municipal health
      centres. Scrutiny of national policy documents and political debate and of the
      course handbooks presented to couples, makes visible a particular Norwegian
      discourse on sexuality, which stresses gender equality and neutrality and ideas
      of inclusive democratization. New parents are advised to make active efforts to
      maintain a loving, lasting relationship and sexuality, for the sake of the
      children. The idea of sex implied by this couples relationship policy is based on
      what might be described as a 'duty of spontaneity', presented as a work both
      parents should undertake in order to achieve a stable and healthy relationship.
      We argue, however, that the inclusive rhetoric of diversity that characterises
      this public form of Norwegian sexuality has its limitations and that certain
      forms of intimacy and sexuality are excluded from this discourse.

PMID- 22616982
TI  - Using a fluorescent cytosine analogue tC(o) to probe the effect of the Y567 to
      Ala substitution on the preinsertion steps of dNMP incorporation by RB69 DNA
      polymerase.
AB  - Residues in the nascent base pair binding pocket (NBP) of bacteriophage RB69 DNA
      polymerase (RB69pol) are responsible for base discrimination. Replacing Tyr567
      with Ala leads to greater flexibility in the NBP, increasing the probability of
      misincorporation. We used the fluorescent cytosine analogue, 1,3-diaza-2
      oxophenoxazine (tC(o)), to identify preinsertion step(s) altered by NBP
      flexibility. When tC(o) is the templating base in a wild-type (wt) RB69pol
      ternary complex, its fluorescence is quenched only in the presence of dGTP.
      However, with the RB69pol Y567A mutant, the fluorescence of tC(o) is also
      quenched in the presence of dATP. We determined the crystal structure of the
      dATP/tC(o)-containing ternary complex of the RB69pol Y567A mutant at 1.9 A
      resolution and found that the incoming dATP formed two hydrogen bonds with an
      imino-tautomerized form of tC(o). Stabilization of the dATP/tC(o) base pair
      involved movement of the tC(o) backbone sugar into the DNA minor groove and
      required tilting of the tC(o) tricyclic ring to prevent a steric clash with L561.
      This structure, together with the pre-steady-state kinetic parameters and dNTP
      binding affinity, estimated from equilibrium fluorescence titrations, suggested
      that the flexibility of the NBP, provided by the Y567 to Ala substitution, led to
      a more favorable forward isomerization step resulting in an increase in dNTP
      binding affinity.

PMID- 22616985
TI  - Novel synthesis and structural analysis of ferrihydrite.
AB  - Naturally occurring ferrihydrite is both impure and difficult to isolate, so the
      numerous applications and interesting properties of ferrihydrite have spurred the
      development of various synthetic techniques. Nearly all techniques are based on
      the hydrolysis of an iron salt and require careful control of temperature, pH,
      and concentration. In this Article, we report a new synthetic method which does
      not require such control and is perhaps the fastest and simplest route to
      synthesizing ferrhydrite. XRD, TEM, BET, and chemical purity characterizations
      show that the chemically pure, 2-line ferrihydrite product consists of
      crystallites 2-6 nm in diameter which aggregate to form mesoporous, high surface
      area agglomerates that are attractive candidates for the many adsorption
      applications of ferrihydrite. X-ray PDF data were also collected for the
      ferrihydrite product and refined against the hexagonal structural model recently
      proposed by Michel et al. These analyses suggest that ferrihydrite has a
      consistent, repeatable structure independent of variation in the synthetic
      method, water content of the sample, or particle size of the crystallites, and
      this structure can be adequately described by the proposed hexagonal model.

PMID- 22616986
TI  - What contributes to the outcomes of moderate and late preterm birth?

PMID- 22616984
TI  - Genomic determinants of organohalide-respiration in Geobacter lovleyi, an unusual
      member of the Geobacteraceae.
AB  - BACKGROUND: Geobacter lovleyi is a unique member of the Geobacteraceae because
      strains of this species share the ability to couple tetrachloroethene (PCE)
      reductive dechlorination to cis-1,2-dichloroethene (cis-DCE) with energy
      conservation and growth (i.e., organohalide respiration). Strain SZ also reduces
      U(VI) to U(IV) and contributes to uranium immobilization, making G. lovleyi
      relevant for bioremediation at sites impacted with chlorinated ethenes and
      radionuclides. G. lovleyi is the only fully sequenced representative of this
      distinct Geobacter clade, and comparative genome analyses identified genetic
      elements associated with organohalide respiration and elucidated genome features
      that distinguish strain SZ from other members of the Geobacteraceae. RESULTS:
      Sequencing the G. lovleyi strain SZ genome revealed a 3.9 Mbp chromosome with
      54.7% GC content (i.e., the percent of the total guanines (Gs) and cytosines (Cs)
      among the four bases within the genome), and average amino acid identities of 53
      56% compared to other sequenced Geobacter spp. Sequencing also revealed the
      presence of a 77 kbp plasmid, pSZ77 (53.0% GC), with nearly half of its encoded
      genes corresponding to chromosomal homologs in other Geobacteraceae genomes.
      Among these chromosome-derived features, pSZ77 encodes 15 out of the 24 genes
      required for de novo cobalamin biosynthesis, a required cofactor for organohalide
      respiration. A plasmid with 99% sequence identity to pSZ77 was subsequently
      detected in the PCE-dechlorinating G. lovleyi strain KB-1 present in the PCE-to
      ethene-dechlorinating consortium KB-1. Additional PCE-to-cis-DCE-dechlorinating
      G. lovleyi strains obtained from the PCE-contaminated Fort Lewis, WA, site did
      not carry a plasmid indicating that pSZ77 is not a requirement (marker) for PCE
      respiration within this species. Chromosomal genomic islands found within the G.
      lovleyi strain SZ genome encode two reductive dehalogenase (RDase) homologs and a
      putative conjugative pilus system. Despite the loss of many c-type cytochrome and
      oxidative-stress-responsive genes, strain SZ retained the majority of Geobacter
      core metabolic capabilities, including U(VI) respiration. CONCLUSIONS: Gene
      acquisitions have expanded strain SZ's respiratory capabilities to include PCE
      and TCE as electron acceptors. Respiratory processes core to the Geobacter genus,
      such as metal reduction, were retained despite a substantially reduced number of
      c-type cytochrome genes. pSZ77 is stably maintained within its host strains SZ
      and KB-1, likely because the replicon carries essential genes including genes
      involved in cobalamin biosynthesis and possibly corrinoid transport. Lateral
      acquisition of the plasmid replicon and the RDase genomic island represent unique
      genome features of the PCE-respiring G. lovleyi strains SZ and KB-1, and at least
      the latter signifies adaptation to PCE contamination.

PMID- 22616988
TI  - MF101: a multi-component botanical selective estrogen receptor beta modulator for
      the treatment of menopausal vasomotor symptoms.
AB  - INTRODUCTION: The Women's Health Initiative Estrogen Plus Progestin clinical
      trial demonstrated the risks exceeded the benefits which have led to a decline in
      menopausal hormone therapy (MHT) by greater than 50%. MHT use was initiated long
      before there was a significant understanding of the molecular mechanisms of
      estrogens. It has become clear that the problem with the current estrogens in MHT
      is they act non-selectively as an agonist in all tissues that contain estrogen
      receptors. MF101 is an oral, botanically derived extract that was designed to
      selectively regulate estrogen receptor beta (ERbeta) because the increased risk
      of breast and endometrial cancer is due to the activation of estrogen receptor
      alpha (ERalpha) by estrogens. Preclinical and clinical data support a role for
      selective ERbeta agonists, such as MF101, for vasomotor symptoms without
      increasing cancer risks. AREAS COVERED: The review covers the biological,
      pharmacological and clinical advantages of MF101, and the unique ability of MF101
      to selectively target the ERbeta pathway for the treatment of hot flashes (HF).
      EXPERT OPINION: Preclinical and clinical studies indicate that MF101, a selective
      estrogen receptor beta agonist, represents a new class of drugs that is safe and
      effective for treating HF and nighttime awakenings.

PMID- 22616989
TI  - Phosphoproteomics of Arabidopsis chloroplasts reveals involvement of the STN7
      kinase in phosphorylation of nucleoid protein pTAC16.
AB  - Light-regulated protein kinases STN7 and STN8 phosphorylate thylakoid membrane
      proteins and also affect expression of several chloroplast proteins via yet
      unknown mechanisms. Comparative phosphoproteomics of acetic acid protein extracts
      of chloroplasts from Arabidopsis thaliana wild type, stn7, stn8 and stn7stn8
      mutants yielded two previously unknown findings: (i) neither STN7 nor STN8 kinase
      was required for phosphorylation of Ser-48 in Lhcb1.1-1.3 proteins; and (ii)
      phosphorylation of Thr-451 in pTAC16 protein was STN7-dependent. pTAC16 was found
      distributed between thylakoids and nucleoid. Its knockout did not affect the
      nucleoid protein composition and the Thr-451 phosphorylated protein was excluded
      from the nucleoid. Thr-451 of pTAC16 is conserved in all studied plants and its
      phosphorylation may regulate membrane-anchoring functions of the nucleoid.

PMID- 22616990
TI  - Modulation of the type I interferon pathways by culture-adaptive hepatitis C
      virus core mutants.
AB  - Hepatitis C virus (HCV) often establishes a persistent infection that leads to
      chronic liver diseases. The viral core protein modulates various cellular
      activities involved in this process. We found two mutations, K23E and V31A, in
      the core gene of the transfected HCV JFH-1 genome, which had been replicated for
      a prolonged period. The mutant viruses escaped immunochemical detection by a core
      specific antibody and demonstrated enhanced RNA replication and protein
      expression, compared to the parental virus. The mutant core proteins bound less
      tightly than the parental type core to the DEAD-box RNA helicase DDX3 and
      attenuated the TBK1-mediated activation of interferon-related promoters. These
      results suggest a mechanism by which the viruses adapt to attenuate cellular
      antiviral activity and to establish persistent infection.

PMID- 22616991
TI  - Expression of the class II tumor suppressor gene RIG1 is directly regulated by
      p53 tumor suppressor in cancer cell lines.
AB  - Recent studies indicated that the RIG1 (RARRES3/TIG3) plays an important role in
      cell proliferation, differentiation, and apoptosis. However, the regulatory
      mechanism of RIG1 gene expression has not been clearly elucidated. In this study,
      we identified a functional p53 response element (p53RE) in the RIG1 gene
      promoter. Transfection studies revealed that the RIG1 promoter activity was
      greatly enhanced by wild type but not mutated p53 protein. Sequence specific
      mutation of the p53RE abolished p53-mediated transactivation. Specific binding of
      p53 protein to the rig-p53RE was demonstrated using electrophoretic mobility
      shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay. Further
      studies confirmed that the expression of RIG1 mRNA and protein is enhanced
      through increased p53 protein in HepG2 or in H24-H1299 cells. In conclusion, our
      results indicated that RIG1 gene is a downstream target of p53 in cancer cell
      lines.

PMID- 22616992
TI  - Relative intensities of recognition factors at two combining sites of Ralstonia
      solanacearum lectin (RSL) for accommodating LFucalpha1-->, DManalpha1--> and
      Galbeta1-->3/4GlcNAc glycotopes.
AB  - Owing to the weak reactivities of monomeric DManalpha1 and Galbeta1-
      >3/4GlcNAcbeta (I(beta)/II(beta)) glycotopes with Ralstonia solanacearum lectin
      (RSL), their recognition roles were previously ignored. In this study, the
      interaction intensities of RSL toward four monomeric glycotopes LFucalpha1-->,
      DManalpha1--> and I(beta)/II(beta) within two combining sites were established by
      both enzyme-linked lectinosorbent and inhibition assays. It was found that high
      density of LFucalpha1--> complex enhanced the recognition intensities at
      LFucalpha1--> site, polyvalent DManalpha1--> was essential for binding at the
      DManalpha1--> site and polyvalent I(beta)/II(beta) was required at LFucalpha1-->
      site. The peculiar recognition systems of RSL are very different from other well
      known microbial lectins.

PMID- 22616993
TI  - Epigenetic regulation of 5-lipoxygenase in the phenotypic plasticity of valvular
      interstitial cells associated with aortic valve stenosis.
AB  - Valvular interstitial cells (VICs) are of mesenchymal origin and may
      differentiate into immune-like cells. This phenotypic plasticity is a key feature
      of aortic valve stenosis, but the role of epigenetic mechanisms has not
      previously been explored. Here we compared normal and calcified human aortic
      valve tissue. Calcified tissue exhibited decreased DNA-methylation in the
      promoter of the gene encoding the proinflammatory enzyme 5-lipoxygenase (5-LO),
      accompanied by increased 5-LO mRNA levels. Treatment of cultured VICs with the
      DNA methyltransferase inhibitor: 5-Aza-2'-deoxycytidine increased 5-LO mRNA
      levels and leukotriene production. These findings provide a first piece of
      evidence for epigenetic modifications of VICs in valvular heart disease.

PMID- 22616994
TI  - Stability of peptide-HLA-I complexes and tapasin folding facilitation--tools to
      define immunogenic peptides.
AB  - Only a small fraction of the peptides generated inside the cell end up being
      presented by HLA-I on the cell surface. High stability of peptide-HLA-I complexes
      and a low HLA-I tapasin-facilitation have been proposed to predict
      immunogenicity. We here set out to investigate if these parameters correlated and
      defined immunogenic peptides. Both peptide-HLA-B(?)08:01 and peptide-HLA
      A(?)02:01 complexes showed small differences in tapasin-facilitation and larger
      differences in stability. This suggests that the stability of immunogenic peptide
      HLA-I complexes vary above an HLA-I allomorph dependent lower limit (e.g. >2h for
      HLA-A(?)02:01), immunogenicity predicted by tapasin-facilitation may be defined
      by an equally allomorph unique upper value (e.g. tapasin-facilitation <1.5 for
      HLA-A(?)02:01), and variation above the stability-threshold does not directly
      reflect a variation in tapasin-facilitation.

PMID- 22616995
TI  - Peripheral benzodiazepine receptor regulates vascular endothelial activations via
      suppression of the voltage-dependent anion channel-1.
AB  - Peripheral benzodiazepine receptor (PBR) is a multifunctional protein mainly
      found on the outer mitochondrial membrane. PBR expression is increased by tumor
      necrosis factor-alpha (TNF-alpha) in endothelial cells. Adenoviral overexpression
      of PBR inhibits monocyte adhesion, VCAM-1, and ICAM-1 expression in TNF-alpha
      activated endothelial cells. Rotenone, cyclosporine A, and bongkrekic acid
      suppress TNF-alpha-induced VCAM-1 expression. Overexpression of PBR inhibits
      voltage-dependent anion channel-1 (VDAC-1) expression and the silencing of PBR
      increases VDAC-1 expression in endothelial cells. Moreover, TNF-alpha-induced
      VCAM-1 expression is suppressed by VDAC-1 gene silencing. PBR overexpression
      significantly decreases TNF-alpha-induced mitochondrial reactive oxygen species
      and MnSOD expression. These results suggest that PBR can inhibit endothelial
      activation and this action is related to the inhibition of mitochondrial ROS
      and/or VDAC-1 expression in endothelial cells.

PMID- 22616996
TI  - Genetic and molecular characterization reveals a unique nucleobase cation
      symporter 1 in Arabidopsis.
AB  - Locus At5g03555 encodes a nucleobase cation symporter 1 (AtNCS1) in the
      Arabidopsis genome. Arabidopsis insertion mutants, AtNcs1-1 and AtNcs1-3, were
      used for in planta toxic nucleobase analog growth studies and radio-labeled
      nucleobase uptake assays to characterize solute transport specificities. These
      results correlate with similar growth and uptake studies of AtNCS1 expressed in
      Saccharomyces cerevisiae. Both in planta and heterologous expression studies in
      yeast revealed a unique solute transport profile for AtNCS1 in moving adenine,
      guanine and uracil. This is in stark contrast to the canonical transport profiles
      determined for the well-characterized S. cerevisiae NCS1 proteins FUR4 (uracil
      transport) or FCY2 (adenine, guanine, and cytosine transport).

PMID- 22616997
TI  - Crystal structure of Pyrococcus furiosus PF2050, a member of the DUF2666 protein
      family.
AB  - Pyrococcus furiosus PF2050 is an uncharacterized putative protein that contains
      two DUF2666 domains. Functional and structural studies of PF2050 have not
      previously been performed. In this study, we determined the crystal structure of
      PF2050. The structure of PF2050 showed that the two DUF2666 domains interact
      tightly, forming a globular structure. Each DUF2666 domain comprises an
      antiparallel beta-sheet and an alpha-helical bundle. One side of the PF2050
      structure has a positively charged basic cleft, which may have a DNA-binding
      function. Furthermore, we confirmed that PF2050 interacts with circular and
      linear dsDNA.

PMID- 22616998
TI  - Diabetes and end of life: ethical and methodological issues in gathering evidence
      to guide care.
AB  - INTRODUCTION: Providing palliative care for people with diabetes at the end of
      life is part of the chronic disease care trajectory, but end of life care is
      complex and the presence of diabetes further complicates management. AIM: The aim
      of the paper is to discuss the ethical and methodological issues encountered when
      undertaking research to develop guidelines for managing diabetes at the end of
      life and the strategies used to address the issues. METHOD: The issues emerged as
      we developed guidelines for managing diabetes at the end of life, which included
      conducting individual interviews with 14 people with diabetes requiring
      palliative care and 10 family members. A reflexive researcher journal was
      maintained throughout the guideline development process. The interview
      transcripts and researcher's journal were analysed to determine key
      methodological, ethical and researcher-related issues. FINDINGS: Key themes were
      vulnerability of the sampling population, methodological issues included
      recruiting participants and ensuring rigor, ethical issues concerned benefit and
      risk, justice, autonomy, privacy, professional boundaries and informed consent.
      Researcher-related issues were identified such as managing participant distress
      and their own emotional distress. People were willing to discuss end of life
      diabetes management preferences. CONCLUSIONS: Undertaking research with people at
      the end of life is complex because of their vulnerability and the ethical issues
      involved. However, the ethical principles of autonomy and justice apply and
      people should be given the relevant information and opportunity to decide whether
      to participate or not.

PMID- 22616999
TI  - Views of young people with depression about family and significant other support:
      interpretative phenomenological analysis study.
AB  - Families and significant others have an important role in helping young people
      cope with depression, but lack of support undermines coping. In this paper, we
      present the views of young people with depression about the role of family and
      significant others in assisting them to cope with their illness. An
      interpretative phenomenological analysis study was undertaken using
      semistructured, audio-recorded interviews with 26 young people diagnosed with
      depression. The findings present two contrasting themes in the data, which
      reflect the young people's views about the influence of families and significant
      others in helping them cope with depression. The first, being supportive,
      highlighted how families and significant others helped through patience,
      tolerance, understanding, and encouragement; all of which strengthened young
      people's resilience as they attempted to cope with depression. The second theme,
      being unsupportive, showed how, in the young people's view, family conflict and
      change, and living in an unsupportive environment, compromised their ability to
      cope with depression. The findings suggest that mental health nurses, other
      clinicians, and primary care practitioners need to increase families' and
      significant others' understandings of depression and their capacity to support
      young people in these circumstances.

PMID- 22617000
TI  - Role of endobronchial ultrasound in diagnosis and molecular assessment of
      metastatic melanoma.
AB  - BACKGROUND AND OBJECTIVE: Vemurafenib is a new inhibitor of the mutated BRAF
      oncogene. In the presence of mutated BRAF in metastatic melanoma, treatment with
      vemurafenib leads to a reduction in mortality and in tumour progression when
      compared with chemotherapy. This study describes nine cases in which
      endobronchial ultrasound (EBUS) guided transbronchial needle aspiration (TBNA)
      was used to assess mediastinal and hilar lymph nodes for the presence of
      metastatic melanoma and demonstrates the ability to detect mutations in BRAF on
      the tissue obtained. METHODS: A retrospective review was performed of all
      patients who had a history of melanoma and underwent EBUS TBNA to investigate
      hilar or mediastinal lymphadenopathy for the presence of metastatic melanoma.
      RESULTS: In seven of the nine cases, metastatic melanoma was confirmed on
      cytology. The two negative cases were proven to be true negatives by follow up or
      by demonstrating an alternate diagnosis. In five cases, analysis for BRAF
      mutation was performed. Four cases were positive for mutation and one
      demonstrated wild-type BRAF. CONCLUSIONS: Tissue samples obtained from EBUS TBNA
      are adequate to diagnose metastatic melanoma in hilar and mediastinal lymph nodes
      and to detect the presence or absence of mutations in the BRAF gene. Our findings
      suggest that close collaboration between bronchoscopists and pathologists will be
      needed to implement BRAF testing in routine practice in the era of targeted
      therapy.

PMID- 22617001
TI  - Mussel-inspired immobilization of vascular endothelial growth factor (VEGF) for
      enhanced endothelialization of vascular grafts.
AB  - Most polymeric vascular prosthetic materials have low patency rate for
      replacement of small diameter vessels (<5 mm), mainly due to failure to generate
      healthy endothelium. In this study, we present polydopamine-mediated
      immobilization of growth factors on the surface of polymeric materials as a
      versatile tool to modify surface characteristics of vascular grafts potentially
      for accelerated endothelialization. Polydopamine was deposited on the surface of
      biocompatible poly(L-lactide-co-epsilon-caprolactone) (PLCL) elastomer, on which
      vascular endothelial growth factor (VEGF) was subsequently immobilized by simple
      dipping. Surface characteristics and composition were investigated by using
      scanning electron microscopy, atomic force microscopy, and X-ray photoelectron
      spectroscopy. Immobilization of VEGF on the polydopamine-deposited PLCL films was
      effective (19.8 +/- 0.4 and 197.4 +/- 19.7 ng/cm(2) for DPv20 and DPv200 films,
      respectively), and biotin-mediated labeling of immobilized VEGF revealed that the
      fluorescence intensity increased as a function of the concentration of VEGF
      solution. The effect of VEGF on adhesion of HUVECs was marginal, which may have
      been masked by polydopamine layer that also enhanced cell adhesion. However, VEGF
      immobilized substrate significantly enhanced proliferation of HUVECs for over 7
      days of in vitro culture and also improved their migration. In addition,
      immobilized VEGF supported robust cell to cell interactions with strong
      expression of CD 31 marker. The same process was effective for immobilization of
      basic fibroblast growth factor, demonstrating the robustness of polydopamine
      layer for secondary ligation of growth factors as a simple and novel surface
      modification strategy for vascular graft materials.

PMID- 22617002
TI  - Diagnostic accuracy of pre-treatment biopsy for grading soft tissue sarcomas in
      dogs.
AB  - Histologic grade is an important prognostic factor for both local recurrence and
      metastatic potential with canine soft tissue sarcoma (STS). Pre-treatment biopsy
      with identification of tumour grade may aid in prognostication and determination
      of surgical margins necessary for local control. The purpose of this study was to
      evaluate the grading accuracy of various pre-treatment biopsy techniques (wedge,
      punch, needle-core) for STS in dogs. Medical records of 68 dogs diagnosed with a
      STS via pre-treatment biopsy and confirmed by excisional biopsy were evaluated.
      The concordance in grade between excisional and pre-treatment biopsies was 59%.
      Of the 41% that lacked concordance, 29% of pre-treatment biopsies underestimated
      and 12% overestimated grade. The method of pre-treatment biopsy did not
      significantly effect grade concordance. Based on these data, needle-core biopsy
      appears to be similar in accuracy compared to open biopsy, however, grading
      determined by pre-treatment biopsy in general should be interpreted with caution.

PMID- 22617004
TI  - Lacrimal sac septum.
AB  - A right orbit was exenterated from a male cadaver that was 85 years of age at
      death. It was microscopically shown for the first time that the lacrimal sac
      septum divided the lumen into two spaces. It consisted of fibrous tissue with a
      cavernous structure and was lined with stratified columnar epithelium similar to
      the lacrimal sac wall.

PMID- 22617003
TI  - Association of gender with outcomes in critically ill patients.
AB  - INTRODUCTION: The influence of gender on mortality and other outcomes of
      critically ill patients is not clear. Different studies have been performed in
      various settings and patient populations often yielding conflicting results. We
      wanted to assess the relationship of gender and intensive care unit (ICU)
      outcomes in the patients included in the Acute Physiology and Chronic Health
      Evaluation (APACHE) IV database (Cerner Corporation, USA). METHODS: We performed
      a retrospective review of the data available in the APACHE IV database. A total
      of 261,255 consecutive patients admitted to adult ICUs in United States from 1
      January 2004 to 31 December 2008 were included. Readmissions were excluded from
      the analysis. The primary objective of the study was to assess the relationship
      of gender with ICU mortality. The secondary objective was to evaluate the
      association of gender with active therapy, mechanical ventilation, length of stay
      in the ICU, readmission rate and hospital mortality. The gender-related outcomes
      for disease subgroups including acute coronary syndrome, coronary artery bypass
      graft (CABG) surgery, sepsis, trauma and chronic obstructive pulmonary disease
      (COPD) exacerbation were assessed as well. RESULTS: ICU mortality was 7.2% for
      men and 7.9% for women, odds ratio (OR) for death for women was 1.07 (95%
      confidence interval (CI): 1.04 to 1.1). There was a statistically significant
      interaction between gender and age. In patients <50 years of age, women had a
      reduced ICU mortality compared with men, after adjustment for acute physiology
      score, ethnicity, co-morbid conditions, pre-ICU length of stay, pre-ICU location
      and hospital teaching status (adjusted OR 0.83, 95% CI: 0.76 to 0.91). But among
      patients >= 50 years of age, there was no significant difference in ICU mortality
      between men and women (adjusted OR 1.02, 95% CI: 0.98 to 1.06). CONCLUSIONS:
      Among the critically ill patients, women less than 50 years of age had a lower
      ICU mortality compared to men, while 50 years of age or older women did not have
      a significant difference compared to men. Women had a higher mortality compared
      to men after CABG surgery and lower mortality with COPD exacerbation. There was
      no difference in mortality in acute coronary syndrome, sepsis or trauma.

PMID- 22617005
TI  - An updated meta-analysis on the effectiveness of preoperative prophylactic
      antibiotics in patients undergoing breast surgical procedures.
AB  - To systematically analyze published randomized trials on the effectiveness of
      preoperative prophylactic antibiotics in patients undergoing breast surgical
      procedures. Trials on the effectiveness of preoperative prophylactic antibiotics
      in patients undergoing breast surgery were selected and analyzed to generate
      summated data (expressed as risk ratio [RR]) by using RevMan 5.0. Nine randomized
      controlled trials encompassing 3720 patients undergoing breast surgery were
      retrieved from the electronic databases. The antibiotics group comprised a total
      of 1857 patients and non-antibiotics group, 1863 patients. There was no
      heterogeneity [chi(2) = 7.61, d.f. = 7, p < 0.37; I(2) = 8%] amongst trials.
      Therefore, in the fixed-effects model (RR, 0.64; 95% CI, 0.50-0.83; z = 3.48; p <
      0.0005), the use of preoperative prophylactic antibiotics in patients undergoing
      breast surgical procedures was statistically significant in reducing the
      incidence of surgical site infection (SSI). Furthermore, in the fixed-effects
      model (RR, 1.30; 95% CI, 0.89-1.90; z = 1.37; p < 0.17), adverse reactions
      secondary to the use of prophylactic antibiotics was not statistically
      significant between the two groups. Preoperative prophylactic antibiotics
      significantly reduce the risk of SSI after breast surgical procedures. The risk
      of adverse reactions from prophylactic antibiotic administration is not
      significant in these patients. Therefore, preoperative prophylactic antibiotics
      in breast surgery patients may be routinely administered. Further research is
      required, however, on risk stratification for SSI, timing and duration of
      prophylaxis, and the need for prophylaxis in patients undergoing breast
      reconstruction versus no reconstruction.

PMID- 22617006
TI  - Hippocampal mGluR5 predicts an occurrence of helplessness behavior after
      repetitive exposure to uncontrollable stress.
AB  - An individual's behavior is generally based on genetic blueprint and previous
      experiences. A coping strategy, affected by personal interpretation of past
      events, can be determined by behavioral controllability of stress. In this study,
      we examined the relationship between the hippocampal mGluR5 expression and coping
      strategies to stress. Rats were exposed to stress via inescapable and
      unpredictable footshocks on PNDs 14 and 90. Coping strategies to stress were also
      measured. Hippocampal mGluR5 was found to be linked to the behavioral coping
      strategy, as it increased in rats that showed helplessness behavior (HL (+)
      group) and decreased in those that did not (HL (-) group). Also, the HL (+) group
      showed a lack of adaptation in a novel environment but the HL (-) group did not.
      The results suggest that mGluR5 has a pivotal role in the controllability-based
      coping strategy. Hippocampal mGluR5 could be a target molecule in the
      manipulation of neuropsychiatric conditions for which maladaptation is a part of
      behavioral consequences.

PMID- 22617007
TI  - A sodium channel myotonia due to a novel SCN4A mutation accompanied by acquired
      autoimmune myasthenia gravis.
AB  - Mutations of the voltage gated sodium channel gene (SCN4A) are responsible for
      non-dystrophic myotonia including hyperkalemic periodic paralysis, paramyotonia
      congenita, and sodium channel myotonia, as well as congenital myasthenic
      syndrome. In vitro functional analyses have demonstrated the non-dystrophic
      mutants to show a gain-of-function defect of the channel; a disruption of fast
      inactivation, an enhancement of activation, or both, while the myasthenic
      mutation presents a loss-of function defect. This report presents a case of non
      dystrophic myotonia that is incidentally accompanied with acquired myasthenia.
      The patient presented a marked warm-up phenomenon of myotonia but the repeated
      short exercise test suggested mutations of the sodium channel. The genetic
      analysis identified a novel mutation, G1292D, of SCN4A. A functional study of the
      mutant channel revealed marked enhancement of activation and slight impairment of
      fast inactivation, which should induce muscle hyperexcitability. The effects of
      the alteration of channel function to the myasthenic symptoms were explored by
      using stimulation of repetitive depolarization pulses. A use-dependent channel
      inactivation was reduced in the mutant in comparison to normal channel, thus
      suggesting an opposing effect to myasthenia.

PMID- 22617009
TI  - Maintaining information online in discrete time; rethinking working memory
      processes.
AB  - Linguistic operations occur with verbal information maintained online for a
      discrete time. It is posited that online maintenance of information is
      accomplished by verbal working memory (WM), a system that is: (a) independent
      from the linguistic operations carried out with the information (specialized),
      and (b) consists of a holding place where information is held in a phonological
      code (phonological loop) and a rehearsal mechanism that refreshes the
      phonological loop. This model does not account for the serial position effects
      associated with information maintenance and additional models are needed to
      explain the latter effects, which leaves us with a disjointed understanding of
      online maintenance of information. In this study, 36 middle-aged, healthy
      subjects (33 males and 3 females) were required to maintain linguistic
      information (letters) online. The letters called upon different cognitive
      operations (orthographic; orthographic and phonetic; or orthographic, phonetic
      and semantic). It was found that online maintenance capacity depends on the
      cognitive operations associated with the letters and on their serial position.
      Additionally, the cognitive operation effect on online maintenance was modulated
      by the serial position. These data favor a model for WM consisting of a simple
      holding place where verbal information maintenance depends on what the
      information is used for. We will discuss an integrated model for online
      information maintenance that accounts for the serial position effects.

PMID- 22617008
TI  - Expression of the P/Q (Cav2.1) calcium channel in nodose sensory neurons and
      arterial baroreceptors.
AB  - The predominant calcium current in nodose sensory neurons, including the
      subpopulation of baroreceptor neurons, is the N-type channel, Cav2.2. It is also
      the primary calcium channel responsible for transmitter release at their
      presynaptic terminals in the nucleus of the solitary tract in the brainstem. The
      P/Q channel, Cav2.1, the other major calcium channel responsible for transmitter
      release at mammalian synapses, represents only 15-20% of total calcium current in
      the general population of sensory neurons and makes a minor contribution to
      transmitter release at the presynaptic terminal. In the present study we
      identified a subpopulation of the largest nodose neurons (capacitance>50pF) in
      which, surprisingly, Cav2.1 represents over 50% of the total calcium current,
      differing from the remainder of the population. Consistent with these
      electrophysiological data, anti-Cav2.1 antibody labeling was more membrane
      delimited in a subgroup of the large neurons in slices of nodose ganglia. Data
      reported in other synapses in the central nervous system assign different roles
      in synaptic information transfer to the P/Q-type versus N-type calcium channels.
      The study raises the possibility that the P/Q channel which has been associated
      with high fidelity transmission at other central synapses serves a similar
      function in this group of large myelinated sensory afferents, including arterial
      baroreceptors where a high frequency regular discharge pattern signals the
      pressure pulse. This contrasts to the irregular lower frequency discharge of the
      unmyelinated fibers that make up the majority of the sensory population and that
      utilize the N-type channel in synaptic transmission.

PMID- 22617010
TI  - The concentrations of serum, plasma and platelet BDNF are all increased by
      treadmill VO2max performance in healthy college men.
AB  - The most current human-based studies in which brain-derived neurotrophic factor
      (BDNF) levels in the peripheral blood system are analyzed use it as an indicator
      that represents BDNF levels in the CNS. However, whether circulating BDNF (serum
      and plasma) is positively or inversely associated with cardiorespiratory fitness
      levels (VO(2max)) is still controversial, and no study has done to investigate
      exercise effects on the concentration of BDNF stored in circulating platelets
      which, in fact, store a large amount of circulating BDNF. Thus, the purpose of
      this study was to determine the relation between VO(2max) and all circulating
      BDNF levels (serum, plasma and platelets) in college male students (N=18; age, 19
      +/- 1 years; height, 173.22 +/- 7.65 cm; weight, 78.25 +/- 14.25 kg; body fat
      percent, 13.82 +/- 5.68%). Dual X-ray energy absorptiometry whole body scan was
      used to measure their body composition. After the overnight fast, all
      participants were performed VO(2max) test, and their blood was collected at rest
      and immediately after the exercise. Our data resulted in significant increases in
      platelet counts and serum, plasma and platelet BDNF levels immediately after the
      exercise (p<0.01). VO(2max) had a significant negative correlation with serum
      BDNF, plasma BDNF and platelet BDNF at rest (p<0.05) but a significant positive
      correlation with serum, plasma BDNF, and platelet BDNF immediately after the
      exercise (p<0.01). However, our data show no correlation between VO(2max) and
      platelet count both at rest and immediately after the exercise. In conclusion,
      this is the first study showing that basal BDNF levels are inversely correlated
      with cardiorespiratory fitness levels but that the inverse correlations turn into
      positive correlations with all circulating BDNF levels immediately after the
      exercise. Moreover, it is the first time to provide evidence that platelet BDNF
      levels are also positively affected by the exercise. However, future studies will
      be needed to investigate what tissues provide BDNF into the circulating system
      and to elucidate the role of circulating BDNF.

PMID- 22617011
TI  - A study to assess the needs of people living with HIV/AIDS reporting to an ART
      Center of Central India.
AB  - Effectively addressing the needs of people living with HIV/AIDS (PLHA) and
      providing them with adequate care and support services are an essential
      intervention necessary to address the problem of HIV. The current study analyzed
      the needs of PLHA, the support received and the support required, to help frame
      comprehensive and focused programs for HIV infected individuals. The study was
      cross-sectional in design, incorporating quantitative analysis techniques and was
      conducted at the Anti Retroviral Therapy (ART) Center of MGM Medical College
      Indore, India, from February 2009 to January 2010. A semistructured interview
      schedule was used to interview 420 respondents currently on ART and the data was
      analyzed using SPSS software. Males and females constituted 69 and 31% of the
      study participants, respectively. The major support received by the respondents
      was care and help from families and friends, free ART, medicines for
      opportunistic infections (OI) and monthly health check-up at the ART Center.
      Other support received included nutritional supplements, traveling allowance to
      travel to the ART Center for availing the monthly dose of ART and educational
      help for children. The major support required was regular availability of
      medicines for various OI and associated diseases at ART centers, free laboratory
      investigations at hospitals, educational help for children, employment
      opportunities, development of a vaccine, facility of households, availability of
      second line ART drugs at ART centers, decentralization of ART centers,
      strengthening of existing PLHA networks and support groups, and better and
      effective counseling services. Coordinated efforts by governmental, non
      governmental sources and PLHA themselves will result in the development of a
      comprehensive package of care and support for PLHA, to cater to their needs and
      requirements.

PMID- 22617012
TI  - Large single crystals of graphene on melted copper using chemical vapor
      deposition.
AB  - A simple method is presented for synthesizing large single crystal graphene
      domains on melted copper using atmospheric pressure chemical vapor deposition
      (CVD). This is achieved by performing the reaction above the melting point of
      copper (1090  degrees C) and using a molybdenum or tungsten support to prevent
      balling of the copper from dewetting. By controlling the amount of hydrogen
      during growth, individual single crystal domains of monolayer graphene greater
      than 200 MUm are produced within a continuous film. Stopping growth before a
      complete film is formed reveals individual hexagonal domains of graphene that are
      epitaxially aligned in their orientation. Angular resolved photoemission
      spectroscopy is used to show that the graphene grown on copper exhibits a linear
      dispersion relationship and no sign of doping. HRTEM and electron diffraction
      reveal a uniform high quality crystalline atomic structure of monolayer graphene.

PMID- 22617014
TI  - Trends in adults receiving a recommendation for exercise or other physical
      activity from a physician or other health professional.
AB  - The Healthy People 2020 objectives for physical activity include two objectives
      for increasing the proportion of physician office visits that include counseling
      or education related to exercise (see
      http://www.healthypeople.gov/2020/default.aspx). Physician counseling for
      exercise has not previously been tracked by the Healthy People initiative. The
      present report looks at this emerging health issue from the vantage point of
      adults in the general population who had seen a physician or other health
      professional in the past 12 months and had been advised to begin or continue to
      do exercise or other physical activity. About 8 in 10 adults had seen a health
      professional in the past 12 months during 2000 (80.6%), 2005 (81.2%), and 2010
      (79.8%), although estimates varied by demographic subgroups (10-12). Over time,
      estimates of the percentage of adults being advised to exercise could be
      influenced by major changes in the characteristics of adults seeing a health
      professional. In 2010, about one in three adults (32.4%) who had seen a physician
      or other health professional in the past year had been advised to exercise or do
      other physical activity, which reflects an upward trend since 2000, moving in the
      direction of meeting Healthy People 2020 goals. In relative terms, there has been
      more than a 40% increase-from 22.6% of adults in 2000 to 32.4% in 2010. Although
      increases were noted for every population and health condition group studied,
      these increases were larger for some groups than others. The increase in the
      percentage of adults receiving exercise advice is particularly noteworthy for the
      oldest age group. In 2000, 15.3% of adults aged 85 and over had been advised to
      exercise; by 2010, the percentage had increased to 28.9%. Across the chronic
      health conditions studied, adults with diabetes were the most likely, and those
      with cancer were the least likely, to have been advised by their physician to
      exercise. An upward trend of 8-10 percentage points, however, was seen among
      adults with each of the chronic diseases examined. Adults who were overweight or
      obese saw among the largest increases over the decade in the percentage receiving
      a physician's advice to exercise. The percentage of healthy weight adults
      receiving exercise advice also increased over the decade, but to a lesser extent.
      Trends over the past 10 years suggest that the medical community is increasing
      its efforts to recommend participation in exercise and other physical activity
      that research has shown to be associated with substantial health benefits. Still,
      the prevalence of receiving this advice remains well below one-half of U.S.
      adults and varies substantially across population subgroups.

PMID- 22617015
TI  - Mesalazine granules 1.5 g once-daily maintain remission in patients with
      ulcerative colitis who switch from other 5-ASA formulations: a pooled analysis
      from two randomised controlled trials.
AB  - BACKGROUND: Mesalazine (mesalamine) granules (MG) were shown to be effective for
      the maintenance of remission of ulcerative colitis (UC) in two double-blind
      placebo-controlled trials. AIM: To evaluate the efficacy of once-daily MG for
      maintenance of remission in patients with UC who switched from other 5
      aminosalicylic acid (5-ASA) formulations. METHODS: Data from two independent
      multicenter, randomised, double-blind, placebo-controlled, 6-month trials
      evaluating patients with UC in remission were combined for analysis of a
      subpopulation of patients who switched from other 5-ASA formulations to MG 1.5 g
      or placebo upon randomisation. The primary endpoint was the percentage of
      patients who remained relapse-free at Month 6 or end of treatment. Relapse was
      defined as a Sutherland Disease Activity Index (SDAI) rectal bleeding score >=1
      and mucosal appearance score >=2, a UC flare or medication used to treat a UC
      flare. RESULTS: Of the 487 patients who received 5-ASA maintenance therapy at
      enrolment, 322 were in the MG group and 165 were in the placebo group. The
      percentage of patients who remained relapse-free (based on Sutherland Disease
      Activity Index scores) after 6 months was significantly higher with MG than
      placebo (78.3% vs. 58.8%, P < 0.001). Rectal bleeding, stool frequency and the
      physician's rating of disease activity remained unchanged after 6 months in a
      higher percentage of patients using MG compared with those on placebo (P < 0.004
      for each endpoint). CONCLUSION: Mesalazine granules 1.5 g once-daily is effective
      for maintenance of remission in UC patients who switch from other 5-ASA
      formulations. ClinicalTrials.gov identifiers NCT00744016, NCT00767728.

PMID- 22617016
TI  - Diastereocontrolled construction of pactamycin's complex ureido triol functional
      array.
AB  - An advanced intermediate in a projected synthesis of pactamycin has been
      prepared. Early installation of the C1-dimethylurea functionality allows for its
      participation in a diastereoselective, chelation-controlled addition of
      organometal nucleophiles to the C5 prochiral ketone. Four of the molecule's six
      stereocenters are set with a ketone functional handle provided for subsequent
      manipulation.

PMID- 22617018
TI  - Lens crystallin response to whole body irradiation with single and fractionated
      doses of gamma radiation.
AB  - PURPOSE: This study was aimed at determining the effect of whole body irradiation
      with single and fractionated low doses of gamma-radiation on the structure of
      normal rats lens crystallin with the concept of correlating this with the changes
      in its molecular weight. MATERIALS AND METHODS: Three groups of Wistar albino
      rats were involved in this study; the first group is the control (n = 10) and the
      second group (n = 10) treated with a single dose of 4.0 Gy administered in one
      application from Cesium-137. The third group (n = 60) was treated for 8 weeks
      with fractionated dose rate of 0.5 Gy/week. Lens crystallin was analysed for
      protein content measurements and column chromatography. RESULTS: Measurements of
      total soluble lens protein indicated pronounced decreases after exposure to
      single and fractionated doses of gamma-radiation. The molecular weights and the
      protein content for the beta(H) (with high molecular weight), beta(L) (with low
      molecular weight) and gamma-crystallin fractions revealed generalized alteration
      for all groups. CONCLUSION: Single and fractionated doses of gamma-radiations
      induced lens crystallin changes that might lead to development of cataract due to
      induction of cross-linking and aggregation. beta(H)-crystallin was the most
      stable against radiation induced damage, and the molecular weight of gamma
      crystallin was the most sensitive to gamma radiation.

PMID- 22617017
TI  - Programmed cell death in Saccharomyces cerevisiae is hampered by the deletion of
      GUP1 gene.
AB  - BACKGROUND: During the past years, yeast has been successfully established as a
      model to study mechanisms of programmed cell death regulation. Saccharomyces
      cerevisiae commits to cell death showing typical hallmarks of metazoan apoptosis,
      in response to different stimuli. Gup1p, an O-acyltransferase, is required for
      several cellular processes that are related to apoptosis development, such as
      rafts integrity and stability, lipid metabolism including GPI anchor correct
      remodeling, proper mitochondrial and vacuole function, bud site selection and
      actin dynamics. Therefore, we hypothesize that apoptotic process would be
      affected by GUP1 deletion. RESULTS: In the present work we used two known
      apoptosis inducing conditions, chronological aging and acetic acid, to assess
      several apoptotic markers in gup1? mutant strain. We found that this mutant
      presents a significantly reduced chronological lifespan as compared to Wt and it
      is also highly sensitive to acetic acid treatment. In addition, it presents
      extremely high levels of ROS. There were notorious differences on apoptotic
      markers between Wt and gup1? mutant strains, namely on the maintenance of plasma
      membrane integrity, on the phosphatidylserine externalization, on the
      depolarization of mitochondrial membrane and on the chromatin condensation. Those
      suggested that the mutant, under either condition, probably dies of necrosis and
      not from apoptosis. CONCLUSIONS: To Gup1p has been assigned an important function
      on lipid rafts assembly/integrity, lipid metabolism and GPI anchor remodeling.
      Our results provide, for the first time, the connection of the integrity of yeast
      lipid rafts and apoptosis induction and/or signaling, giving new insights into
      the molecular mechanisms underlying this process in yeast.

PMID- 22617019
TI  - A comparison of cordocentesis outcomes between early and conventional procedures.
AB  - OBJECTIVE: To compare procedural outcomes between early cordocentesis (16-17
      weeks) and those at 18-22 weeks. MATERIALS AND METHODS: A prospective database of
      cordocentesis was assessed. The eligible criteria included are (1) singleton
      pregnancy; (2) no fetal abnormalities; (3) gestational age of 16-22 weeks and (4)
      procedures performed by experienced operators. The procedures performed during 16
      17 weeks were defined as early cordocentesis (Study group). The Control group
      (conventional cordocentesis; 18-22 weeks) were selected by matching maternal age
      and years of procedures, with a ratio of 1:3. RESULTS: Of 2942 eligible
      procedures, 103 procedures were undertaken during 16-17 weeks and 309 matched
      controls were selected. Baseline characteristics of both groups were comparable.
      Time used to complete the procedure was significantly longer in Study group (8.45
      +/- 9.91 vs. 6.07 +/- 6.63 min; p value 0.007). Similarly, rate of difficult
      procedures was significantly higher in Study group (7.8 vs. 2.3%; p value 0.011).
      However, rates of fetal loss, low birth weight infants and preterm births were
      not significantly different, but there was a tendency to be higher in Study
      group. CONCLUSION: Early cordocentesis is more difficult but relatively safe when
      performed by experienced hands, although it has a tendency to increase rates of
      adverse outcomes. This information may be helpful in counseling the couples.

PMID- 22617020
TI  - Consumption of sugar drinks in the United States, 2005-2008.
AB  - One-half of the U.S. population consumes sugar drinks on any given day, and 25%
      consumes at least 200 kcal (more than one 12-oz can of cola). Sugar-drink
      consumption differs by sex, age, race and ethnicity, and income. For example,
      males consume more than females, and teenagers and young adults consume more than
      other age groups. Among adults, non-Hispanic black and Mexican-American persons
      consume more than non-Hispanic white persons, and low-income individuals consume
      more sugar drinks in relation to their total diet than higher-income individuals.
      More than one-half of sugar drinks are consumed in the home. Most sugar drinks
      consumed away from home are obtained from stores, but more than one-third are
      obtained in restaurants or fast-food establishments.

PMID- 22617022
TI  - Partial halogenation of cyclic and branched perhydropentasilanes.
AB  - The perhydropentasilanes (H(3)Si)(4)Si and Si(5)H(10) were chlorinated with
      SnCl(4) to give chlorohydropentasilanes without destruction of the Si-Si
      backbone. Tetrachloroneopentasilane (ClH(2)Si)(4)Si (2) was prepared in high
      yield from (H(3)Si)(4)Si and 3.5 equiv of SnCl(4), while Si(5)H(10) and an
      equimolar amount of SnCl(4) afforded a mixture of ~60% of ClSi(5)H(9) (1) with
      polychlorinated cyclopentasilanes and unreacted starting material, which could
      not be separated by distillation. The selective monochlorination of Si(5)H(10)
      was achieved starting from MesSi(5)Cl(9) (3; Mes = 2,4,6-trimethylphenyl) or
      TBDMP-Si(5)Cl(9) (4; TBDMP = 4-tert-butyl-2,6-dimethylphenyl). 3 or 4 was
      successfully hydrogenated with LiAlH(4) to give MesSi(5)H(9) (6) or TBDMP
      Si(5)H(9) (7), which finally gave 1 along with aryl-H and Si(5)H(10) after
      treatment with an excess of liquid anhydrous HCl. All compounds were
      characterized by standard spectroscopic techniques. For Si-H derivatives, the
      coupled (29)Si NMR spectra were analyzed in detail to obtain an unequivocal
      structural assignment. The molecular structures of 2-4 were further confirmed by
      X-ray crystallography.

PMID- 22617021
TI  - A brief historical account of Madrid's qanats.

PMID- 22617023
TI  - In vitro template-dependent synthesis of Pepino mosaic virus positive- and
      negative-strand RNA by its RNA-dependent RNA polymerase.
AB  - Pepino mosaic virus (PepMV)-infected tomato plants were used to develop an in
      vitro template-dependent system for the study of viral RNA synthesis.
      Differential sedimentation and sucrose-gradient purification of PepMV-infected
      tomato extracts resulted in fractions containing a transcriptionally active
      membrane-bound RNA-dependent RNA polymerase (RdRp). In the presence of Mg(2+)
      ions, (32)P-labelled UTP and unlabelled ATP, CTP, GTP, the PepMV RdRp catalysed
      the conversion of endogenous RNA templates into single- and double-stranded (ds)
      genomic RNAs and three 3'-co-terminal subgenomic dsRNAs. Hybridisation
      experiments showed that the genomic ssRNA was labelled only in the plus strand,
      the genomic dsRNA mainly in the plus strand and the three subgenomic dsRNAs
      equally in both strands. Following removal of the endogenous templates from the
      membrane-bound complex, the purified template-dependent RdRp could specifically
      catalyse transcription of PepMV virion RNA, in vitro-synthesized full-length plus
      strand RNA and the 3'-termini of both the plus- and minus-strand RNAs. Rabbit
      polyclonal antibodies against an immunogenic epitope of the PepMV RdRp (anti
      RdRp) detected a protein of approximately 164kDa in the membrane-bound and
      template-dependent RdRp preparations and exclusively inhibited PepMV RNA
      synthesis when added to the template-dependent in vitro transcription system. The
      300 nucleotides long 3'-terminal region of the PepMV genome, containing a stretch
      of at least 20 adenosine (A) residues, was an adequate exogenous RNA template for
      RdRp initiation of the minus-strand synthesis but higher transcription efficiency
      was observed as the number of A residues increased. This observation might
      indicate a role for the poly(A)-tail in the formation and stabilisation of
      secondary structure(s) essential for initiation of transcription. The template
      dependent specific RdRp system described in this article will facilitate
      identification of RNA elements and host components required for PepMV RNA
      synthesis.

PMID- 22617025
TI  - The natural alkaloid berberine targets multiple pathways to induce cell death in
      cultured human colon cancer cells.
AB  - In the current paper, berberine, an isoquinoline alkaloid, was tested for its
      chemopreventive potential in colon cancer (SW480) cells. Berberine inhibited
      proliferation of colon cancer cells in a dose- and time-dependent manner.
      Interestingly, this compound exhibited minimum toxicity in normal cells at 200
      MUM. Berberine arrested SW480 cell cycle at G2/M phase, which was supported by
      induction of p21 expression. Induction of a series of biochemical events,
      including loss of mitochondrial membrane potential, release of cytochrome-c to
      cytosol, induction of Bcl-2 family proteins, caspases and cleavage of poly (ADP
      ribose) polymerase (PARP), by berberine suggests its ability to induce apoptosis.
      In addition, berberine also inhibited inflammation, as evidenced by induction of
      expression of NFkappaB and Cox(2). Furthermore, berberine inhibited caspase-8
      mediated angiogenesis, as confirmed through expression of tumor necrotic factor
      related apoptosis-inducing ligand (TRAIL), vascular endothelial growth factor
      (VEGF) and survivin. The results of the current study demonstrated that berberine
      has the ability to cause cell cycle arrest, induce apoptosis and inhibit
      inflammation in colon cancer cells. The magnitude of the effects observed
      suggests that berberine may be worth considering for further studies of its
      potential applications for improving health, either as a preventative or a
      potential treatment.

PMID- 22617024
TI  - Comparative in vivo analysis of the nsp15 endoribonuclease of murine, porcine and
      severe acute respiratory syndrome coronaviruses.
AB  - The purpose of this study was to compare the biochemical and biological
      properties of nonstructural protein (nsp) 15 among mouse hepatitis virus (MHV),
      severe acute respiratory syndrome coronavirus (SARS-CoV) and transmissible
      gastroenteritis virus (TGEV) in virus-infected and ectopically expressed cells.
      In virus-infected cells, MHV nsp15 distributed unevenly throughout the cytoplasm
      but predominantly in the perinuclear region. When expressed as N-terminal
      enhanced green fluorescence protein (EGFP) fusion, it predominantly formed
      speckles in the cytoplasm. In contrast, SARS-CoV and TGEV EGFP-nsp15s distributed
      smoothly in the whole cell and did not form speckles. Deletion mapping
      experiments identified two domains responsible for the speckle formation in MHV
      EGFP-nsp15: Domain I (aa101-150) and Domain III (aa301-374). Interestingly,
      Domain II (aa151-250) had an inhibitory effect on Domain III- but not on Domain I
      mediated speckle formation. Expression of a small (35aa) sequence in Domain III
      alone was sufficient to form speckles for all 3 viral nsp15s. However, addition
      of surrounding sequences in Domain III abolished the speckle formation for TGEV
      nsp15 but not for MHV and SARS-CoV nsp15s. Further domain swapping experiments
      uncovered additional speckle-inducing and -suppressive elements in nsp15s of SARS
      CoV and TGEV. Homotypic interaction involving Domain III of MHV nsp15 was further
      demonstrated biochemically. Moreover, the biological functions of the expressed
      nsp15s were assessed in MHV-infected cells. It was found that the effects of EGFP
      nsp15s on MHV replication were both virus species- and nsp15 domain-dependent.
      Collectively these results thus underscore the differential biochemical and
      biological functions among the nsp15s of MHV, TGEV and SARS-CoV in host cells.

PMID- 22617027
TI  - Repair and regeneration of tracheal surface epithelium and submucosal glands in a
      mouse model of hypoxic-ischemic injury.
AB  - BACKGROUND AND OBJECTIVE: The heterotopic syngeneic tracheal transplant mouse
      model is an acute hypoxic-ischemic injury model that undergoes complete repair
      and regeneration. We hypothesized that the repair and regeneration process of the
      surface epithelium and submucosal glands would occur in a reproducible pattern
      that could be followed by the expression of specific markers of epithelial cell
      types. METHODS: We used the syngeneic heterotopic tracheal transplant model to
      develop a temporal and spatial map of cellular repair and regeneration by
      examining the tracheal grafts at post-transplant days 1, 3, 5, 7, 10 and 14. We
      used pulsed BrdU and immunofluorescent staining to identify and follow
      proliferating and repairing cell populations. RESULTS: We confirmed the
      reproducibility of the injury and repair in the model and we found a distinct
      sequence of reappearance of the various stem/progenitor and differentiated cell
      populations of the tracheal surface epithelium and submucosal glands. In the
      initial phase, the basal and duct cells that survived the injury proliferated to
      re-epithelialize the basement membrane with K5 and K14 expressing cells. Then
      these cells proliferated further and differentiated to restore the function of
      the epithelium. During this repair process, TROP-2 marked all repairing
      submucosal gland tubules and ducts. Non-CCSP-expressing serous cells were found
      to differentiate 4-5 days before Clara, mucus and ciliated cells. CONCLUSIONS:
      Improving our understanding of the reparative process of the airway epithelium
      will allow us to identify cell-specific mechanisms of repair that could be used
      as novel therapeutic approaches for abnormal repair leading to airway diseases.

PMID- 22617026
TI  - The alpha1-, but not alpha2-, adrenoceptor in the nucleus accumbens plays an
      inhibitory role upon the accumbal noradrenaline and dopamine efflux of freely
      moving rats.
AB  - In vivo microdialysis was used to analyse the role of the alpha(1)- and alpha(2)
      adrenoceptor subtypes in the regulation of noradrenaline and dopamine efflux in
      the nucleus accumbens of freely moving rats. Intra-accumbal infusion of alpha(1)
      adrenoceptor agonist methoxamine (24pmol) failed to alter the noradrenaline
      efflux, but decreased the dopamine efflux. The intra-accumbal infusion of
      alpha(1)-adrenoceptor antagonist prazosin (6, 600 and 6000pmol) produced a dose
      related increase and decrease of the noradrenaline and dopamine efflux,
      respectively. An ineffective dose of prazosin (6pmol) counteracted the
      methoxamine (24pmol)-induced decrease of dopamine efflux. The prazosin (6000pmol)
      induced increase of noradrenaline efflux, but not the decrease of dopamine
      efflux, was suppressed by the co-administration of an ineffective dose of
      methoxamine (0.024pmol). Neither the alpha(2)-adrenoceptor agonist clonidine
      (300pmol) and UK 14,304 (300pmol) nor the alpha(2)-adrenoceptor antagonist RX
      821002 (0.6, 3, 600 and 6000pmol) significantly affected the accumbal
      noradrenaline and dopamine efflux. The doses mentioned are the total amount of
      drug over the 60-min infusion period. The present results show that (1) accumbal
      alpha(1)-adrenoceptors which are presynaptically located on noradrenergic nerve
      terminals inhibit the accumbal noradrenaline efflux, increasing thereby the
      accumbal dopamine efflux, (2) accumbal alpha(1)-adrenoceptors which are
      postsynaptically located on dopaminergic nerve terminals inhibit the accumbal
      dopamine efflux, and (3) accumbal alpha(2)-adrenoceptors play no major role in
      the regulation of accumbal efflux of noradrenaline and dopamine.

PMID- 22617028
TI  - Xanthones from fungi, lichens, and bacteria: the natural products and their
      synthesis.

PMID- 22617031
TI  - Effects of low intensity ultrasound on cellulase pretreatment.
AB  - This research was to explore the mechanism of ultrasonic impact on free cellulase
      activity and immobilize cellulase activities. The highest free cellulase activity
      was achieved when the sample was treated with low intensity ultrasound at 15 W,
      24 kHz for 10 min, under which the enzyme activity was increased by 18.17% over
      the control. Fluorescence and CD spectra revealed that the ultrasonic treatment
      had increased the number of tryptophan on cellulase surface slightly, with the
      deformation of certain number of alpha-helix structure and increase of random
      coil content in cellulase protein. The highest immobilized cellulase activity was
      achieved when the sample was treated with low intensity ultrasound at 60 W, 24
      kHz for 10 min, under which the enzyme activity was increased by 24.67% over the
      control. Scanning electron microscopy revealed that the ultrasonic treatment had
      increased the surface area of immobilized cellulase.

PMID- 22617030
TI  - A transformation in the mechanism by which the urokinase receptor signals
      provides a selection advantage for estrogen receptor-expressing breast cancer
      cells in the absence of estrogen.
AB  - Binding of urokinase-type plasminogen activator (uPA) to its receptor, uPAR, in
      estrogen receptor-alpha (ERalpha) expressing breast cancer cells, transiently
      activates ERK downstream of FAK, Src family kinases, and H-Ras. Herein, we show
      that when uPAR is over-expressed, in two separate ERalpha-positive breast cancer
      cell lines, ERK activation occurs autonomously of uPA and is sustained.
      Autonomous ERK activation by uPAR requires H-Ras and Rac1. A mutated form of
      uPAR, which does not bind vitronectin (uPAR-W32A), failed to induce autonomous
      ERK activation. Expression of human uPAR or mouse uPAR but not uPAR-W32A in MCF-7
      cells provided a selection advantage when these cells were deprived of estrogen
      in cell culture for two weeks. Similarly, MCF-7 cells that express mouse uPAR
      formed xenografts in SCID mice that survived and increased in volume in the
      absence of estrogen supplementation, probably reflecting the pro-survival
      activity of phospho-ERK. Autonomous uPAR signaling to ERK was sensitive to the
      EGFR tyrosine kinase inhibitors, Erlotinib and Gefitinib. The transition in uPAR
      signaling from uPA-dependent and transient to autonomous and sustained is
      reminiscent of the transformation in ErbB2/HER2 signaling observed when this gene
      is amplified in breast cancer. uPAR over-expression may provide a pathway for
      escape of breast cancer cells from ERalpha-targeting therapeutics.

PMID- 22617029
TI  - Regulation of VEGF signaling by membrane traffic.
AB  - Recent findings have drawn attention to the role of membrane traffic in the
      signaling of vascular endothelial growth factor (VEGF). The significance of this
      development stems from the pivotal function of VEGF in vasculogenesis and
      angiogenesis. The outline of the regulation of VEGF receptor (VEGFR) signaling by
      membrane traffic is similar to that of the epidermal growth factor receptor
      (EGFR), a prototype of the intertwining between membrane traffic and signaling.
      There are, however, unique features in VEGFR signaling that are conferred in part
      by the involvement of the co-receptor neuropilin (Nrp). Nrp1 and VEGFR2 are
      integrated into membrane traffic through the adaptor protein synectin, which
      recruits myosin VI, a molecular motor that drives inward trafficking [17,21,64].
      The recent detection of only mild vascular defects in a knockin mouse model that
      expresses Nrp1 lacking a cytoplasmic domain [104], questions the co-receptor's
      role in VEGF signaling and membrane traffic. The regulation of endocytosis by
      ephrin-B2 is another feature unique to VEGR2/3 [18,19], but it awaits a
      mechanistic explanation. Current models do not fully explain how membrane traffic
      bridges between VEGFR and the downstream effectors that produce its functional
      outcome, such as cell migration. VEGF-A appears to accomplish this task in part
      by recruiting endocytic vesicles carrying RhoA to internalized active VEGFR2
      [58].

PMID- 22617032
TI  - Biological pretreatment for production of lignocellulosic biofuel.
AB  - Lignocellulosic biomass was submitted to a biological pretreatment prior to a
      catalytic hydroliquefaction in order to produce biofuel. The biodegradation
      process was conducted over 3 months in a reactor under controlled conditions.
      During the biodegradation process the organic matter was characterised and its
      evolution was correlated with physico-chemical parameters. In parallel with the
      analysis of the lipidic fraction, analytical pyrolysis was used to monitor
      bacterial activity. The alterations of branched to linear fatty acids ratio and
      of mono- to diacids ratio were compared when determined by thermochemolysis and
      observed in the directly extractable lipids. The evolution of the phytol to the
      corresponding isoprenoic ketone ratio was observed to be dependent on the
      desorption technique since it decreases using headspace while it increases using
      pyrolysis. "Humic"/"fulvic acids" ratio, infrared spectroscopy and
      thermodifferential analysis were used to determine the degree of OM
      complexification.

PMID- 22617033
TI  - Dynamic model of temperature impact on cell viability and major product formation
      during fed-batch and continuous ethanolic fermentation in Saccharomyces
      cerevisiae.
AB  - The impact of the temperature on an industrial yeast strain was investigated in
      very high ethanol performance fermentation fed-batch process within the range of
      30-47  degrees C. As previously observed with a lab strain, decoupling between
      growth and glycerol formation occurred at temperature of 36  degrees C and
      higher. A dynamic model was proposed to describe the impact of the temperature on
      the total and viable biomass, ethanol and glycerol production. The model
      validation was implemented with experimental data sets from independent cultures
      under different temperatures, temperature variation profiles and cultivation
      modes. The proposed model fitted accurately the dynamic evolutions for products
      and biomass concentrations over a wide range of temperature profiles. R2 values
      were above 0.96 for ethanol and glycerol in most experiments. The best results
      were obtained at 37  degrees C in fed-batch and chemostat cultures. This dynamic
      model could be further used for optimizing and monitoring the ethanol
      fermentation at larger scale.

PMID- 22617034
TI  - Effect of ionic liquid pretreatment on the chemical composition, structure and
      enzymatic hydrolysis of energy cane bagasse.
AB  - Ionic liquids (ILs) are promising solvents for the pretreatment of lignocellulose
      as they are thermally stable, environmentally friendly, recyclable, and have low
      volatility. This study evaluated the effect of 1-ethyl-3-methylimidazolium
      acetate ([EMIM][OAc]) for the pretreatment of energy cane bagasse in terms of
      biomass composition, structural changes and enzymatic digestibility. Energy cane
      bagasse was pretreated with [EMIM][OAc] (5% (w/w)) at 120  degrees C for 30 min
      followed by hydrolysis with commercially available enzymes, Spezyme CP and
      Novozyme 188. IL-treated energy cane bagasse resulted in significant lignin
      removal (32.0%) with slight glucan and xylan losses (8.8% and 14.0%,
      respectively), and exhibited a much higher enzymatic digestibility (87.0% and
      64.3%) than untreated (5.5% and 2.8%) or water-treated (4.0% and 2.1%) energy
      cane bagasse in terms of both cellulose and hemicellulose digestibilities,
      respectively. The enhanced digestibilities of IL-treated biomass can be
      attributed to delignification and reduction of cellulose crystallinity as
      confirmed by FTIR and XRD analyses.

PMID- 22617035
TI  - A novel potential source of beta-carotene: Eustigmatos cf. polyphem
      (Eustigmatophyceae) and pilot beta-carotene production in bubble column and flat
      panel photobioreactors.
AB  - Carotenoids profile of the unicellular Eustigmatos cf. polyphem
      (Eustigmatophyceae) and beta-carotene production of the microalga in bubble
      column and large flat panel bioreactors were studied. The microalga which
      contained beta-carotene, violaxanthin and vaucheriaxanthin as the major
      carotenoids accumulated large amount of beta-carotene. The beta-carotene
      production of this microalga in the bubble column bioreactor was considerable,
      with the maximum intracellular beta-carotene content reaching 60.76 mg g(-1),
      biomass reaching 9.2 g L(-1), and beta-carotene yield up to 470.2 mg L(-1). The
      beta-carotene productions in two large flat panel bioreactors were relatively
      lower, whereas over 100 mg beta-carotene L(-1) was achieved. Besides, high light
      intensity helped to accumulate intracellular beta-carotene and biomass. Deficient
      nitrate supply inhibited biomass growth, though it helped to accumulate beta
      carotene. Our results first proved that E. cf. polyphem was a potential source
      and producer of beta-carotene, making it an interesting subject for further beta
      carotene study or commercial exploration.

PMID- 22617036
TI  - Co-pyrolysis characteristics of microalgae Chlorella vulgaris and coal through
      TGA.
AB  - To find out an alternative of coal saving, a kind of microalgae, Chlorella
      vulgaris (C. vulgaris) which is widespread in fresh water was introduced into
      coal pyrolysis process. In this work, the pyrolysis experiments of C. vulgaris
      and coal blend (CCB) were carried out by TGA, and those of C. vulgaris and coal
      were also taken respectively as control groups. It was found that: the TG and DTG
      profiles of CCB were similar to C. vulgaris, but different from coal under
      various blending ratios; DTG profiles of CCB were different at several heating
      rates; interaction was observed between the solid phases of CCB; kinetic triplets
      were determined by the Kissinger-Akahira-Sunose (KAS), Flynn-Wall-Ozawa (FWO),
      and master-plots method, respectively. The results provide a reference for
      further study on co-pyrolysis of microalgae and coal to a certain extent.

PMID- 22617037
TI  - Carbon sources influence the nitrate removal activity, community structure and
      biofilm architecture.
AB  - Influence of the frequently used carbon sources in nitrate removal processes were
      evaluated in a lab-scale biofilm reactor. The NO3-N removal efficiency was in the
      order acetate>glucose>methanol>ethanol. Acetate-fed biofilm reduced nearly 100%
      NO3-N with negligible amount of NO2-N accumulation. Although 99% NO3-N was
      reduced in the glucose-fed biofilm, substantial NH3-N and NO2-N accumulated.
      Methanol-fed biofilm reduced 72% of NO3-N with accumulation of 2.2 mg L(-1) of
      NO2-N, while biofilm formed in presence of ethanol showed 61% reduction in NO3-N
      although relatively higher ratio of denitrifiers were observed. Acetate and
      ethanol-fed biofilm displayed characteristic biofilm architecture with voids, but
      the former had relatively higher thickness and diffusion distance. In presence of
      glucose and methanol, a confluent biofilm without characteristic voids was
      formed. Pseudomonas sp. numerically dominated the acetate and ethanol-fed
      biofilm, while Enterobacter sp. and Methylobacillus sp., were abundant in glucose
      and methanol biofilms respectively.

PMID- 22617038
TI  - A modified dynamic respiration test to assess compost stability: effect of sample
      size and air flowrate.
AB  - Goal of this work was to study the effect of the unit air flowrate on dynamic
      respiration activity indexes during the assessment of compost stability. A MSW
      compost was used and six experimental runs were performed with variable compost
      masses and variable air flowrates, so that to achieve six unit air flowrates (6,
      9, 16, 17, 23 and 30 L air kg(-1) organic matter h(-1)). Six respiration activity
      indexes were quantified, namely a dynamic respiration index (DRI24), the
      cumulative O2 consumption at 4 and 7 days (DCRI4, DCRI7), a CO2 index, the
      cumulative CO2 generation after 7 days (Total CO2) and the respiratory quotient.
      Results indicate that the CO2 related indexes and the respiratory quotients had a
      strong negative correlation with the unit air flowrate, whilst the DRI24 and both
      DCRIs slightly increased with increasing unit air flowrates.

PMID- 22617039
TI  - Saccharification of woody biomass using glycoside hydrolases from Stereum
      hirsutum.
AB  - Enzymatic saccharification of woody biomasses was performed using glycoside
      hydrolases from Stereum hirsutum, a newly isolated fungal strain found to secrete
      efficient glycoside hydrolases. The strain showed the highest beta-glucosidase,
      cellobiohydrolase, endoglucanase, endoxylanase, laccase, and filter paper
      activity of 10.3, 1.7, 10.3, 29.9, 0.12, and 0.58 U/ml, respectively. Among the
      various biomasses tested for saccharification, pine biomass produced maximum
      reducing sugar. Response surface methodology was used to optimize the hydrolysis
      of pine biomass to achieve the highest level of sugars. The parameters including
      enzyme, substrate concentration, temperature and pH were found to be critical for
      the conversion of pine biomass into sugars. Maximum saccharification of 49.7%
      (435 mg/g-substrate) was obtained after 96 h of hydrolysis. A close agreement
      between the experimental results and the model predictions was achieved. S.
      hirsutum could be a good choice for the production of reducing sugars from
      cellulosic biomasses.

PMID- 22617040
TI  - Combining metabolic engineering and adaptive evolution to enhance the production
      of dihydroxyacetone from glycerol by Gluconobacter oxydans in a low-cost way.
AB  - Gluconobacter oxydans can rapidly and effectively transform glycerol to
      dihydroxyacetone (DHA) by membrane-bound quinoprotein sorbitol dehydrogenase
      (mSLDH). Two mutant strains of GDHE Deltaadh pBBR-PtufBsldAB and GDHE Deltaadh
      pBBR-sldAB derived from the GDHE strain were constructed for the enhancement of
      DHA production. Growth performances of both strains were largely improved after
      adaptively growing in the medium with glucose as the sole carbon source. The
      resulting GAT and GAN strains exhibited better catalytic property than the GDHE
      strain in the presence of a high concentration of glycerol. All strains of GDHE,
      GAT and GAN cultivated on glucose showed enhanced catalytic capacity than those
      grown on sorbitol, indicating a favorable prospect of using glucose as carbon
      source to reduce the cost in industrial production. It was also the first time to
      reveal that the expression level of the sldAB gene in glucose-growing strains
      were higher than that of the strains cultivated on sorbitol.

PMID- 22617043
TI  - Consumption of added sugar among U.S. children and adolescents, 2005-2008.
AB  - Approximately 16% of children and adolescents' total caloric intakes came from
      added sugars. Boys consumed more added sugars than girls. Preschool-aged children
      consumed the fewest calories from added sugars. Although girls consumed a smaller
      absolute amount of calories from added sugars than boys, their intakes were not
      that different from boys when the amounts are expressed as a percentage of total
      caloric intakes. Non-Hispanic white children and adolescents consumed a larger
      percentage of their calories from added sugars than Mexican-American children and
      adolescents. Also, Non-Hispanic black girls consumed a larger percentage of their
      calories from added sugars than Mexican-American girls. There was very little
      difference in added sugar consumption based on PIR. More of the added sugars
      calories came from foods as opposed to beverages. Previous research has
      demonstrated that sodas are the single leading food source of added sugars
      intakes among children, adolescents, and adults (2,4). Our results showed a
      little more than 40% of calories from added sugars came from beverages. Poti and
      Popkin (5) have suggested that eating location impacts daily energy intake in
      children and adolescents and that foods prepared away from home, are contributing
      to their increased total energy intake. Our results showed that more of the added
      sugars calories were consumed at home rather than away from home. A substantial
      percentage of calories in the diets of children and adolescents between 2005 and
      2008 came from added sugars. According to the 2010 Dietary Guidelines "reducing
      the consumption of these sources of added sugars will lower the caloric content
      of the diet, without compromising its nutrient adequacy (3)." This strategy could
      play an important role in reducing the high prevalence of obesity in the United
      States (6) without compromising adequate nutrition.

PMID- 22617041
TI  - Anaerobic treatment of sewage sludge containing selective serotonin reuptake
      inhibitors.
AB  - The selective serotonin reuptake inhibitors citalopram, sertraline, paroxetine,
      fluvoxamine and fluoxetine have been investigated in 10 l anaerobic lab-scale
      digesters with continuous stirring and mesophilic conditions at 37  degrees C to
      investigate whether they would be reduced or accumulated in sewage sludge
      depending on whether the bacteria present were able to use the SSRIs as a carbon
      source or not. The total SSRI concentration had a significant reduction in
      concentration during the anaerobic treatment process from theoretically 0.58 mg/l
      to 0.21 mg/l after 17 days. However, large differences in the reduction of the
      different compounds were found. Paroxetine and citalopram were found to be almost
      completely reduced at day 24 with reductions of 85% (citalopram) and 98%
      (paroxetine). Reductions of 32% (fluoxetine), 53% (fluvoxamine) and 38%
      (sertraline) indicate that these three compounds have a higher potential for
      accumulation. None metabolites of these compounds were found in the samples.

PMID- 22617042
TI  - The Gly(972)Arg variant of human IRS1 gene is associated with variation in
      glomerular filtration rate likely through impaired insulin receptor signaling.
AB  - The objective of this study is to identify and characterize the genetic variants
      related to the glomerular filtration rate (GFR) linkage on 2q37. Of the
      positional candidate genes, we selected IRS1 and resequenced its 2-kb promoter
      region and exons for sequence variants in 32 subjects. A total of 11 single
      nucleotide polymorphisms (SNPs) were identified. To comprehensively cover the 59
      kb-long intron-1, eight additional tagging SNPs were selected from the HapMap.
      All the 19 SNPs were genotyped by TaqMan Assay in the entire data set (N = 670;
      39 families). Association analyses between the SNPs and GFR and type 2 diabetes
      related traits were performed using the measured genotype approach. Of the SNPs
      examined for association, only the Gly(972)Arg variant of IRS1 exhibited a
      significant association with GFR (P = 0.0006) and serum triglycerides levels (P =
      0.003), after accounting for trait-specific covariate effects. Carriers of Arg972
      had significantly decreased GFR values. Gly(972)Arg contributed to 26% of the
      linkage signal on 2q. Expression of IRS1 mutant Arg972 in human mesangial cells
      significantly reduced the insulin-stimulated phosphorylation of IRS1 and Akt
      kinase. Taken together, the data provide the first evidence that genetic
      variation in IRS1 may influence variation in GFR probably through impaired
      insulin receptor signaling.

PMID- 22617044
TI  - The effect of DN (dominant-negative) Ku70 and reoxygenation on hypoxia cell-kill:
      evidence of hypoxia-induced potentially lethal damage.
AB  - PURPOSE: To study the effect of DN (dominant-negative) Ku70 and reoxygenation on
      the hypoxia-induced cell-kill. MATERIALS AND METHODS: Cell lines were human
      colorectal carcinoma HCT8 and HT29 cells and their respective derivatives, v-HCT8
      and v-HT29 infected with DNKu70-containing adenovirus. Cells were plated in glass
      tubes and made hypoxic by flushing N(2) gas containing 0, 0.1 or 0.5% O(2). Cell
      survival was determined by colony formation assay immediately after 0-96 h
      hypoxia. To reoxygenate medium were replaced fresh following 48 or 72 h in
      hypoxia and cells were incubated in aerobic environment for 2-24 h before
      survival assay. RESULTS: When incubated in hypoxia, cells lost reproductive
      capability ~ exponentially as a function of time in hypoxia, and depending on the
      O(2) concentration. DNKu70 rendered cells more prone to hypoxia-induced cell
      kill. Following reoxygenation cell survival increased rapidly but without
      detectable cell proliferation during first 24 hours. This evinced hypoxia-induced
      potentially lethal damage (PLD) that was repairable upon reoxygenation. DNKu70
      did not significantly inhibit this repair. CONCLUSION: Hypoxia-induced cell
      lethality was facilitated by DNKu70, but substantially repaired upon
      reoxygenation. This may have negative impact on the effect of reoxygenation in
      cancer therapy.

PMID- 22617045
TI  - Blood pressure measurements at emergency department visits by adults: United
      States, 2007-2008.
AB  - This brief shows that elevated BP readings are much more common at visits to the
      ED than at visits to outpatient primary care providers. Compared with the 27.0%
      prevalence found at visits to primary care providers, the combined visit
      prevalence of severely and moderately elevated BP in EDs is about 43.5%.
      Disproportionately affected subgroups include patients who are older, male, non
      Hispanic black, Medicare beneficiaries, or uninsured.One reason that elevated BP
      may be observed more frequently in the ED than at visits to primary care
      providers is that adults in less than optimal general health are more likely to
      use the ED than those in good health (4). Two national objectives related to
      prevention of heart disease and stroke are (a) to reduce the proportion of adults
      with hypertension and (b) to increase the proportion of adults with hypertension
      whose BP is under control (5). ED visits could provide opportunities to address
      elevated BP through patient education, initial treatment, and referral to primary
      care as deemed clinically appropriate.

PMID- 22617046
TI  - Cystathionine beta-synthase deficiency causes infertility by impairing
      decidualization and gene expression networks in uterus implantation sites.
AB  - Hyperhomocysteinemia has been reported in human reproduction as a risk factor for
      early pregnancy loss, preeclampsia, and congenital birth defects like spina
      bifida. Female infertility was also observed in cystathionine beta synthase
      deficient mice (Cbs-KO) as an animal model for severe hyperhomocysteinemia. The
      aim for the present research was to elucidate the time-point of pregnancy loss
      and to pinpoint gene and cellular changes involved in the underlying pathological
      mechanism. By mating 90-day-old wild-type and Cbs-KO female mice with their
      homologous male partners, we found that pregnancy loss in Cbs-KO occurred between
      the 8th and 12th gestation day during placenta formation. DNA microarrays were
      carried out on uterus from implantation and interimplantation samples obtained on
      day 8. The results allowed us to select genes potentially involved in embryo
      death; these were individually confirmed by RT-qPCR, and their expressions were
      also followed throughout pregnancy. We found that changes in expression of Calb1,
      Ttr, Expi, Inmt, Spink3, Rpgrip1, Krt15, Mt-4, Gzmc, Gzmb, Tdo2, and Afp were
      important for pregnancy success, since a different regulation in Cbs-KO mice was
      found. Also, differences in relationships among selected genes were observed,
      indicating a dysregulation of these genes in Cbs-KO females. In conclusion, our
      data provide more information on the gene expression cascade and its timely
      regulated process required for a successful pregnancy. In addition, we unveil new
      potential avenues to explore further investigations in pregnancy loss.

PMID- 22617047
TI  - A mass balance approach to resolving LNAPL stability.
AB  - This article explores the hypothesis that natural losses of light nonaqueous
      phase liquids (LNAPLs) through dissolution and evaporation can control the
      overall extent of LNAPL bodies and LNAPL fluxes observed within LNAPL bodies.
      First, a proof-of-concept sand tank experiment is presented. An LNAPL (methyl
      tert-butyl ether) was injected into a sand tank at five constant injection rates
      that were increased stepwise. Initially, for each injection rate the LNAPL bodies
      expanded quickly. With time the rate of expansion of the LNAPL bodies slowed and
      at extended times the extent of the LNAPL became constant. Attainment of a stable
      LNAPL extent is attributed to rates of LNAPL addition being equal to rates of
      LNAPL losses through dissolution and evaporation. Secondly, analytical solutions
      are developed to extrapolate the processes observed in the proof-of-concept
      experiment to dimensions and time frames that are consistent with field-scale
      LNAPL bodies. Three LNAPL body geometries that are representative of common field
      conditions are considered including one-dimensional, circular, and oblong shapes.
      Using idealized conditions, the solutions describe volumetric LNAPL fluxes as a
      function of position in LNAPL bodies and the overall extent of LNAPL bodies as a
      function of time. Results from both the proof-of-concept experiment and the
      mathematical developments illustrate that natural losses of LNAPL can play an
      important role in governing LNAPL fluxes within LNAPL bodies and the overall
      extent of LNAPL bodies.

PMID- 22617048
TI  - Effects of structural flexibility of wings in flapping flight of butterfly.
AB  - The objective of this paper is to clarify the effects of structural flexibility
      of wings of a butterfly in flapping flight. For this purpose, a dynamics model of
      a butterfly is derived by Lagrange's method, where the butterfly is considered as
      a rigid multi-body system. The panel method is employed to simulate the flow
      field and the aerodynamic forces acting on the wings. The mathematical model is
      validated by the agreement of the numerical result with the experimentally
      measured data. Then, periodic orbits of flapping-of-wings flights are
      parametrically searched in order to fly the butterfly models. Almost periodic
      orbits are found, but they are unstable. Deformation of the wings is modeled in
      two ways. One is bending and its effect on the aerodynamic forces is discussed.
      The other is passive wing torsion caused by structural flexibility. Numerical
      simulations demonstrate that flexible torsion reduces the flight instability.

PMID- 22617049
TI  - Proposed MHRA changes to UK children's paracetamol dosing recommendations:
      modelling study.
AB  - OBJECTIVES: Paracetamol is the most commonly administered medicine to children. A
      recent study highlighted the risk of overdose of paracetamol using British
      National Formulary for Children (BNFC) age-based dosing guidelines. This current
      study assesses the safety of changes to the UK paracetamol product dosing system
      proposed by the Medicines and Healthcare products Regulatory Authority (MHRA)
      which include a larger number of narrower age bands and a single dose per age
      band. DESIGN: Theoretical comparison of the proposed MHRA dosing system with the
      product dosing instructions of a commonly prescribed form of paracetamol in the
      UK. SETTING: United Kingdom Participants Proposed MHRA dosing recommendations and
      current product dosing instructions were compared using a previously validated
      model. MAIN OUTCOME MEASURES: For both dosing recommendations, single and
      cumulative daily doses of paracetamol for boys and girls at the 9th, 50th and
      91st centiles for weight were calculated for 3 month, 1 year, 6 year and 12 year
      age groups. RESULTS: With the current product dosing instructions, underweight
      children are at risk of receiving approximately two times the recommended single
      and cumulative daily dose of paracetamol, particularly at age 1 year and 6 years.
      This risk is negligible when the same model is applied to the proposed MHRA
      dosing system, whereby underweight, average weight and overweight children at all
      ages receive doses marginally above or within the recommended dose range or
      limit. CONCLUSION: The proposed MHRA dosing recommendations for paracetamol use
      in children are effective at reducing the risk of paracetamol overdose in
      children of all ages, when compared with current product dosing instructions.

PMID- 22617050
TI  - Monte Carlo simulations to support start-up and treatment planning of scanned
      proton and carbon ion therapy at a synchrotron-based facility.
AB  - Reliable treatment planning of highly conformal scanned ion beam therapy demands
      accurate tools for the determination and characterization of the individual
      pencil-like beams building up the integral dose delivery and related mixed
      radiation field. At present, clinically practicable inverse treatment planning
      systems (TPSs) can only rely on fast-performing analytical algorithms. However,
      the rapidly emerging though more computationally intensive Monte Carlo (MC)
      methods can be employed to complement analytical TPS, e.g., via accurate
      calculations of the input beam-model data, together with a considerable reduction
      of the measuring time. Here we present the work done for the application of the
      FLUKA MC code to support several aspects of scanned ion beam delivery and
      treatment planning at the Heidelberg Ion Beam Therapy Center (HIT). Emphasis is
      given to the generation of the accelerator library and of experimentally
      validated TPS input basic data which are now in clinical use for proton and
      carbon ion therapy. Additionally, MC dose calculations of planned treatments in
      water are shown to represent a valuable tool for supporting treatment plan
      verification in comparison to dosimetric measurements. This paper can thus
      provide useful information and guidelines for the start-up and clinical operation
      of forthcoming ion beam therapy facilities similar to HIT.

PMID- 22617052
TI  - Metal-only Lewis pairs with transition metal lewis bases.

PMID- 22617051
TI  - Abacavir induces loading of novel self-peptides into HLA-B*57: 01:  an autoimmune
      model for HLA-associated drug hypersensitivity.
AB  - BACKGROUND: Abacavir drug hypersensitivity in HIV-treated patients is associated
      with HLA-B57:01 expression. To understand the immunochemistry of abacavir drug
      reactions, we investigated the effects of abacavir on HLA-B57:01 epitope-binding
      in vitro and the quality and quantity of self-peptides presented by HLA-B57:01
      from abacavir-treated cells. DESIGN AND METHODS: An HLA-B57:01-specific epitope
      binding assay was developed to test for effects of abacavir, didanosine or
      flucloxacillin on self-peptide binding. To examine whether abacavir alters the
      peptide repertoire in HLA-B57:01, a B-cell line secreting soluble human leucocyte
      antigen (sHLA) was cultured in the presence or absence of abacavir, peptides were
      eluted from purified human leucocyte antigen (HLA), and the peptide epitopes
      comparatively mapped by mass spectroscopy to identify drug-unique peptides.
      RESULTS: Abacavir, but not didansosine or flucloxacillin, enhanced binding of the
      FITC-labeled self-peptide LF9 to HLA-B57:01 in a dose-dependent manner.
      Endogenous peptides isolated from abacavir-treated HLA-B57:01 B cells showed
      amino acid sequence differences compared with peptides from untreated cells.
      Novel drug-induced peptides lacked typical carboxyl (C) terminal amino acids
      characteristic of the HLA-B57:01 peptide motif and instead contained
      predominantly isoleucine or leucine residues. Drug-induced peptides bind to
      soluble HLA-B57:01 with high affinity that was not altered by abacavir addition.
      CONCLUSION: Our results support a model of drug-induced autoimmunity in which
      abacavir alters the quantity and quality of self-peptide loading into HLA-B57:01.
      Drug-induced loading of novel self-peptides into HLA, possibly by abacavir either
      altering the binding cleft or modifying the peptide-loading complex, generates an
      array of neo-antigen peptides that drive polyclonal T-cell autoimmune responses
      and multiorgan systemic toxicity.

PMID- 22617053
TI  - Transcatheter transcaval embolization of a type II endoleak after EVAR using a
      transseptal needle-sheath system.
AB  - PURPOSE: The purpose of this study is to present an alternative technique for
      management of a type II endoleak associated with aneurysm sac enlargement.
      TECHNIQUE: We report the use of a transseptal needle-sheath system for a
      transcatheter transcaval embolization (TTE) in a 3-staged treatment of a
      persistent type II endoleak after abdominal EVAR. Inferior vena cava is
      cannulated through a femoral venous access, and aneurysmal sac access is gained
      with a puncture through the walls of the 2 vessels at the site where the vein is
      adjacent to the aneurysm. The whole system (sheath-dilator-needle) is then
      advanced across the vascular walls into the aortic sac. Thus, embolization with
      glue is performed. CONCLUSION: The TTE using a transseptal needle-sheath system
      demonstrated to be feasible and effective to treat a persistent type II endoleak
      after failure of 2 attempts of transarterial embolization of the feeding vessels.

PMID- 22617054
TI  - Con:  mesh in vaginal surgery:  do the risks outweigh the benefits?
AB  - PURPOSE OF REVIEW: To provide an overview regarding the results of transvaginal
      mesh kits to determine if the known risks outweigh their benefits. RECENT
      FINDINGS: Two Federal and Drug Administration warnings and an ever-increasing
      amount of data in medical journals reveal a paucity of support regarding routine
      transvaginal mesh kits for the treatment of pelvic organ prolapse. There have
      been no studies showing improved quality of life when compared to nonmesh
      repairs. There have been no studies showing superiority of mesh kits over
      traditional procedures for posterior or apical prolapses, and minimal data
      suggesting anatomic benefit of synthetic mesh for anterior compartment repairs.
      In contrast, transvaginal mesh use significantly increases the complication rate
      over nonmesh repairs. Some of these complications cause lifelong, irreversible
      pelvic pain, vaginal shortening, vaginal narrowing, severe vaginal pain, and
      dyspareunia. SUMMARY: Transvaginal synthetic mesh kits have minimal to no
      improved clinical success over nonmesh repairs. Compounding this, mesh kits are
      clearly associated with multiple relatively common and unique complications
      without any significant proven benefit for symptomatic relief of pelvic organ
      prolapse and improvement of quality of life. Continued routine use will
      needlessly and potentially harm patients permanently without providing any
      significant benefit.

PMID- 22617055
TI  - Pro:  the contemporary use of transvaginal mesh in surgery for pelvic organ
      prolapse.
AB  - PURPOSE OF REVIEW: This review will focus on the strengths of transvaginal mesh
      augmented repairs over traditional native tissue repairs with an emphasis on the
      more recent literature. RECENT FINDINGS: Recent attention from the Food and Drug
      Administration has prompted a re-evaluation of the use of commercial mesh kits in
      pelvic organ prolapse (POP) repair. Mesh kits for POP repair were recently
      reclassified from Class 2 medical devices to Class 3 medical devices, a policy
      change that will prompt additional trials for POP repair in the future. The
      statements published by the FDA and the reclassification of mesh kits have
      generated a debate regarding the use of mesh in POP repairs. SUMMARY: Higher
      complication rates involving mesh exposures have been documented in the past
      leading to the recent controversy; however, current mesh studies with longer term
      follow-up show lower and acceptable exposures with improved objective and
      subjective outcomes.

PMID- 22617056
TI  - Native tissue repairs in anterior vaginal prolapse surgery:  examining
      definitions of surgical success in the mesh era.
AB  - PURPOSE OF REVIEW: Native tissue repair of the anterior vaginal wall was thought
      to have a poor success rate based on anatomic outcome. This high rate of anatomic
      failure was often quoted as the underlying reason for performing mesh-augmented
      prolapse repair. The purpose of this article is to review the outcomes of native
      tissue repair of anterior vaginal prolapse repair in the mesh era. RECENT
      FINDINGS: Success in pelvic organ prolapse surgery has been redefined. The
      contemporary definition of success includes the absence of symptoms associated
      with a vaginal bulge, which correlates best with a patient's perception of
      success. When this concept is applied to 12 randomized controlled trials that
      compared native tissue anterior colporrhaphy and mesh repairs for anterior
      vaginal wall prolapse, it is apparent that although mesh repair had superior
      anatomic success (38-93 vs. 27-71%), both mesh and native tissue repair had
      excellent rates of symptomatic success (75-96 and 62-100%, respectively). Taken
      together, the overall reoperation rate for native tissue repair was 5.0% compared
      with 9.0% for mesh-augmented repair. SUMMARY: Although anatomic stage 0 results
      are not achieved in many cases, patients do experience symptomatic relief and
      improvement in their quality of life, only seeking retreatment in a small
      proportion of cases with anatomic recurrence. Thus, the definition of success
      must include subjective symptom-based outcome in addition to anatomic outcome. In
      addition, the degree of later complications, including additional surgeries, must
      also be taken into account when defining success based on patient satisfaction.

PMID- 22617057
TI  - Vaginal mesh update.
AB  - PURPOSE OF REVIEW: As more women undergo repairs of pelvic organ prolapse (POP),
      an ever-increasing scrutiny has been placed on repairs utilizing vaginal mesh. We
      aim to review the current literature regarding mesh POP repairs and discuss the
      Food and Drug Administration controversy. RECENT FINDINGS: Evidence-based
      literature indicates that the objective success of standard (plication-type)
      repairs in the anterior compartment may not be durable, and that augmentation
      with nonabsorbable, synthetic mesh may be superior. Augmentation in the posterior
      compartment may not present a clear advantage over standard repair. Transvaginal
      mesh used for POP repair may be associated with adverse sequelae, such as
      erosion, extrusion, and infection. Additionally, there is concern regarding
      potential long-term outcomes such as dyspareunia, chronic pelvic pain, and
      vaginal distortion, which may occur even in the absence of frank extrusion.
      Recent warnings by the Food and Drug Administration regarding adverse events
      after transvaginal mesh implantation have led to a call for an increase in the
      premarket testing and postmarket surveillance of these products. SUMMARY:
      Although the use of transvaginal mesh may improve anatomical outcomes over
      standard repairs, the subjective improvement may be similar. Furthermore, the
      recent warnings regarding mesh placement may lead to a greater level of
      regulation of these products.

PMID- 22617058
TI  - Complications of vaginal mesh surgery.
AB  - PURPOSE OF REVIEW: Mesh used for slings and pelvic organ prolapse (POP) repair
      has resulted in increased efficacy. Yet, the benefits of a more durable repair
      must be weighed against such risks as vaginal mesh extrusion and erosion and
      increased dyspareunia, and pelvic pain. We review the current literature on
      complications seen with the use of vaginal mesh for both stress urinary
      incontinence and POP. RECENT FINDINGS: The use of mesh in midurethral slings
      results in similar efficacy but less morbidity compared with nonmesh sling
      techniques. The use of mesh in abdominal sacrocolpopexy may result in lower rates
      of mesh complications compared with transvaginal mesh prolapse repairs. In 2011,
      the Food and Drug Administration issued an updated safety communication stating
      that serious complications associated with transvaginal mesh for POP repair are
      not rare. Yet, certain patients do benefit from the use of transvaginal mesh for
      POP repair. SUMMARY: Better-controlled data are needed to answer questions
      regarding outcomes, complications, and quality of life after transvaginal mesh
      prolapse procedures. The surgeon and the patient must have a proper informed
      consent discussion about the risks, benefits, alternatives, and indications for
      the use of mesh.

PMID- 22617059
TI  - MRI-guided and robotic-assisted prostate biopsy.
AB  - PURPOSE OF REVIEW: In this review, we summarized and critically discussed the
      most recent developments in the field of MRI-compatible robot-guided prostate
      interventions. RECENT FINDINGS: Currently, systematic transrectal ultrasound
      guided prostate biopsy for prostate cancer detection is the standard of care.
      Multiparametric MRI providing anatomic, functional and molecular information is
      the most promising imaging technique to detect and localize prostate cancer. A
      number of MRI-compatible robots, ranging from simple manipulators to a fully
      automated system, have been developed. The feasibility of these MRI-compatible
      robotic devices in closed-bore systems for prostatic interventions have been
      investigated. However, most studies focused on phantom experiments rather than on
      patients' studies. Thus far, only a small number of patients have undergone MRI-
      guided and robotic-assisted prostate biopsy. Although this potential technique
      shows promising results, there is little evidence for its clinical applicability.
      SUMMARY: The combination of MRI-guided and robotic-assisted prostate biopsy is a
      promising technique for prostate cancer detection. However, only limited research
      is performed in patients, and therefore the current clinical value of this
      technique is highly speculative.

PMID- 22617060
TI  - Multiparametric MRI and prostate cancer diagnosis and risk stratification.
AB  - PURPOSE OF REVIEW: Prostate cancer is the most common solid organ cancer type
      among American men. Screening and imaging aim to detect early-stage disease that
      is biologically aggressive. The focus of this study is to review multiparametric
      MRI in the detection and risk stratification of prostate cancer. RECENT FINDINGS:
      MP-MRI has been shown to be the most accurate noninvasive technique to localize
      prostate cancer. Recent studies reported that using MRI for guidance during
      prostate biopsies increases the yield of prostate biopsies. Moreover,
      multiparametric and particular MRI sequences such as apparent diffusion
      coefficient values of diffusion-weighted MRI have been found to correlate
      negatively with tumor Gleason scores. SUMMARY: Among the existing imaging
      modalities, multiplanar magnetic resonance is the best at detecting prostate
      cancers. Some risk stratification is possible based on size, extent and apparent
      diffusion coefficient values. However, prostate MRI remains nonspecific and
      biopsies must be performed to confirm whether an abnormality is benign or
      malignant and to assign Gleason scores.

PMID- 22617061
TI  - Value of contrast-enhanced ultrasonography in prostate cancer.
AB  - PURPOSE OF REVIEW: Traditional grayscale ultrasonography has poor discrimination
      between benign and malignant areas within the prostate. Current biopsy techniques
      commonly miss prostate cancer when present within the gland, with the majority of
      prostate biopsies negative for cancer. Enhanced ultrasound (US) modalities may
      improve the visualization of the prostate and better detect foci of prostate
      cancer. These enhanced US modalities include intravenous contrast enhancement, to
      better visualize areas with increased blood flow within the prostate, which may
      be indicative of latent prostate cancer. We reviewed the current literature for
      contrast-enhanced transrectal prostate ultrasonography. RECENT FINDINGS: Numerous
      American and international studies demonstrate improved prostate cancer detection
      when contrast-enhanced US biopsy techniques are used. Enhanced US modalities
      include the use of harmonic imaging and flash replenishment techniques, as well
      as quantitative measurement of blood flow within the prostate. Vascular areas
      visualized with these techniques targeted for prostate biopsy yield improved
      prostate cancer detection rates. US contrast microbubbles linked to antibodies or
      small molecules may also allow targeted visualization and delivery of agents to
      the prostate. SUMMARY: Enhanced US modalities with intravenous contrast
      enhancement dramatically improve vascular imaging and resolution within the
      prostate. Targeted biopsies have higher yield for prostate cancer detection, and
      may prove useful for the initial evaluation of patients with elevated serum
      prostate-specific antigen levels, as well as for patients with persistently
      elevated prostate-specific antigen after negative prostate biopsy.

PMID- 22617064
TI  - [A girl with a painful hip after a splits].
AB  - A 14-year-old girl had a painful hip after making a splits on a trampoline. On X
      ray we discovered an avulsion fracture of the spina iliaca anterior superior,
      which healed in 6 weeks with conservative treatment.

PMID- 22617062
TI  - Molecular imaging of prostate cancer.
AB  - PURPOSE OF REVIEW: Prostate cancer is a complex and biologically heterogeneous
      disease that is not adequately assessed with conventional imaging alone.
      Molecular imaging with positron emission tomography (PET) is poised to fill this
      unmet need through noninvasive probing of the multiple molecular and cellular
      processes that are active in prostate cancer patients. RECENT FINDINGS: Several
      PET tracers are active in early-stage and late-stage prostate cancer in humans.
      F18-Fluorodeoxyglucose (FDG), C11/F18-choline and sodium F18-fluoride have been
      studied most extensively. There is a growing body of literature supporting the
      utility of choline in early-stage prostate cancer. FDG and sodium F18-fluoride
      are more valuable in advanced disease, especially for assessing bone metastases,
      the prevalent form of metastases in this patient population. F18
      fluorodihydrotestosterone is active in castrate disease and is emerging as a
      valuable pharmacodynamic marker in the development of novel androgen receptor
      targeted therapies. Prostate-specific membrane antigen PET tracers are in the
      early stages of clinical development. SUMMARY: Multiple PET tracers are currently
      available to aid in the detection and management of prostate cancer across the
      clinical spectrum of the disease. Prospective, rigorously controlled, clinical
      imaging trials are needed to establish the optimal role of PET in prostate
      cancer.

PMID- 22617065
TI  - [Causes of decreased use of peritoneal dialysis as a kidney replacement therapy
      in the Netherlands].
AB  - OBJECTIVE: To study the extent and causes of the declining use of peritoneal
      dialysis (PD) as kidney replacement therapy in patients with end-stage renal
      disease in the Netherlands. DESIGN: Retrospective cohort study. METHOD: The
      prevalence and incidence of various kidney replacement therapies in the
      Netherlands from 1995 to 2010 were analysed. Also the 5-year outflow of patients
      on PD or haemodialysis (HD) from 1995 to 2006 was analysed using the cumulative
      incidence competing risks method and Cox regression analysis. RESULTS: The
      absolute number of patients starting PD between 1995 and 2008 was stable at about
      400 per year. There was a relative decline in the use of PD in the total dialysis
      population from 15% in 1995 to 8% in 2010. This decrease was seen in both large
      and small centres and was related to a relative increase in the numbers
      undergoing HD (67% before 2001, 74% in 2009), and kidney transplantation before
      dialysis (3% before 2002, 9% in 2009), as well as a decrease in change of therapy
      from HD to PD. The increased number starting on HD was associated with the growth
      of the incident patient group aged 65 years or older, most of whom (80-85%)
      underwent HD. Within the younger group (0-65 years) there was an increase in
      numbers on HD and in the number of pre-emptive transplantations. CONCLUSION: The
      decline in the prevalence of PD was partly explained by the relative increase in
      numbers starting HD, associated with an ageing patient population, fewer people
      changing from HD to PD therapy, and the increased number of kidney
      transplantations before dialysis in younger patients. The increasing prevalence
      of HD has been made possible by growth of the HD capacity.

PMID- 22617066
TI  - [Guideline 'Diagnostics of small-vessel vasculitis'].
AB  - The multidisciplinary guideline 'Diagnostics of small-vessel vasculitis' gives
      recommendations for the diagnostics of small-vessel vasculitis, which is often
      associated with cutaneous manifestations. The aim of this guideline is to
      accelerate the diagnostic process to prevent or reduce irreversible organ damage.
      The clinical presentation of small-vessel vasculitis is variable and often
      atypical. The most common general symptoms are general malaise, unexplained
      fever, weight loss, fatigue, loss of appetite, and night sweats. If these
      symptoms are accompanied by one or more organ-specific symptoms, the probability
      of the diagnosis 'small-vessel vasculitis' is increased. When small-vessel
      vasculitis is suspected a comprehensive history should be taken and a physical
      examination focused on internal organs, joints, skin and nervous system should be
      performed. With additional laboratory investigations possible organ involvement
      can be demonstrated and the small-vessel vasculitis can be further classified. To
      make a definite diagnosis histological examination of an affected organ is
      necessary. Because of the possible involvement of multiple organ systems,
      multidisciplinary collaboration is essential in the diagnostic work-up.

PMID- 22617067
TI  - [Iodine deficiency due to an abnormal diet].
AB  - BACKGROUND: In the past, iodine deficiency was an important cause of goitre and
      mental retardation. Since the introduction of iodised salt the incidence of
      iodine deficiency has declined enormously. CASE DESCRIPTION: An 8-year old girl
      had goitre for several months. Her diet was modified to take into account
      supposed food allergies. She never ate bread products and no salt was added to
      the food on the assumption that salt is harmful. The thyroid stimulating hormone
      (TSH) level was not abnormal, the free T4 value was reduced and the T3 value high
      to normal. Urine investigation indicated reduced iodine excretion. Echography
      demonstrated a diffusely enlarged thyroid. The iodine deficiency was successfully
      treated with oral iodine supplementation. CONCLUSION: This case report shows that
      iodine deficiency based on an inadequate iodine intake still occurs in the
      Netherlands. An increase in supposed allergies and subsequent decrease of iodine
      supplementation in the diet may lead to a higher frequency of this "forgotten"
      disease.

PMID- 22617068
TI  - [Orthostatic tremor: unsteadiness while standing still].
AB  - We present three patients with histories of the typical unsteady feeling in the
      legs while standing still which disappears when walking or sitting down. An
      orthostatic tremor is a disorder that is difficult to recognise because patients
      describe balance disturbances rather than tremors. Clinical findings include a
      fine tremor in the legs which may be invisible but can be heard on auscultation
      and felt on palpation of the leg muscles. The diagnosis is confirmed by EMG which
      reveals a pathognomonic tremor of 13-18 Hz while the patient is standing upright.
      Its pathophysiology is unknown but a disorder related to proprioceptive feedback
      has been suggested. The tremor can be associated with Parkinson's disease,
      Graves' disease, and cerebellar or pontine lesions which should be excluded by
      laboratory investigations and MRI. There is little evidence available on
      effective treatments, but clonazepam seems to be the first drug of choice,
      followed by gabapentin. Levodopa can be tried in patients with parkinsonism.

PMID- 22617069
TI  - [Diagnostic importance of the alveolar-arterial oxygen gradient].
AB  - BACKGROUND: The alveolar-arterial (A-a) oxygen gradient is the difference between
      the partial pressure of oxygen in the alveoli and the partial pressure of
      arterial oxygen and can be elevated in the case of pulmonary disease. CASE
      DESCRIPTION: We describe a 41-year-old patient with pneumonia who presented with
      abdominal pain, in whom calculation of the A-a gradient could have led to earlier
      diagnosis. CONCLUSION: The A-a oxygen gradient is mainly of diagnostic importance
      and the presented nomogram allows easy and quick interpretation. This might lead
      to a more frequent use of the A-a oxygen gradient in the future.

PMID- 22617070
TI  - [Consent for the secondary use of human residual tissue: the patient is best
      served by an 'opting-out' procedure].
AB  - In medical scientific research much use is made of human bodily material
      (residual tissue) which remains after treatment or diagnosis. Using this,
      relevant research questions can be answered. The way in which patients can
      consent to the secondary use of residual tissue is now formalised in a code of
      conduct, which allows such use unless the patient has objected to this use
      ('opting-out' procedure). A law is being formulated which will probably require
      the explicit permission of the patient for secondary use of residual tissue. It
      is expected that this requirement will lead to a lesser and more selective
      availability of residual tissue for research. Requesting explicit permission also
      means additional health care work. Patients demonstrate a preference for the
      'opting-out' procedure, on condition that they are well informed about the use of
      the residual tissue. It is concluded that the interests of the patient are best
      served by the 'opting-out' procedure, provided that patients are well informed.

PMID- 22617071
TI  - [Osteogenesis imperfecta: clinical and genetic heterogeneity].
AB  - Osteogenesis imperfecta is a hereditary connective tissue disorder characterized
      primarily by fractures with no or small causal antecedent; in most patients this
      is a consequence of diminished or abnormal production of collagen type I. It is a
      clinically heterogeneous disorder: it has been proposed recently to classify
      osteogenesis imperfecta in types I-V on the basis of the clinical picture and
      radiology. It is also a genetically heterogeneous disorder; 90% of cases are due
      to autosomal dominant mutations, while the remaining 10% are due to autosomal
      recessive mutations or of unknown cause. Osteogenesis imperfecta type I and to a
      lesser extent type IV are important differential diagnostic considerations in
      case of suspicion of non-accidental injury (NAI). When osteogenesis imperfecta is
      suspected, DNA analysis of the dominant COL1A1 and COL1A2 genes is currently the
      starting point for laboratory diagnosis unless there are strong indications for a
      recessive cause. Protein analysis based on skin biopsy remains indicated in
      specific cases.

PMID- 22617072
TI  - [Increasing abdominal girth in a female patient with a gastric band].
AB  - BACKGROUND: Insufficient weight loss after gastric band placement is generally
      linked to band-related complications or a persistently unhealthy diet. CASE
      DESCRIPTION: A 47-year-old woman with a history of gastric band placement
      presented with complaints of decreased mobility, dyspnoea, gastro-oesophageal
      reflux and a progressive increase in abdominal girth. Initially, these symptoms
      were attributed to an unhealthy diet. However, additional testing showed a large
      intra-abdominal multicystic lesion originating from the ovaries. The patient was
      operated and two large serous cystadenomas were removed, after which the symptoms
      disappeared almost immediately. CONCLUSION: Abdominal complaints after bariatric
      surgery can often be explained by surgical complications or unhealthy eating
      habits. Although the cause of certain complaints is sometimes obvious,
      alternative diagnoses need to be considered. If the abdominal girth in middle
      aged women increases, ovarian disorders must always be considered in the
      differential diagnosis and appropriate additional diagnostic testing need to be
      carried out.

PMID- 22617073
TI  - [Vacuum-assisted closure therapy for exposed vascular prosthesis in the groin].
AB  - Groin infections are a severe complication in vascular surgery. The treatment of
      a groin infection with exposed vascular prosthetic material is challenging.
      Vacuum-assisted closure (VAC) is a therapy frequently used to close wounds. In
      groin wounds with exposed vascular prosthetic material, however, VAC has been
      contraindicated because of the risk of bleeding. We successfully treated 17 groin
      infections with exposed vascular prosthetic material from 2009 to 2011 by using a
      double-sponge technique (a combination of polyvinyl alcohol and polyurethane
      sponges and a continuous negative pressure of 50 mmHg); there were no
      complications involving haemorrhaging, amputations or re-infection. At a median
      follow-up duration of 380 days, no further complications occurred and all
      prostheses could be retained. The double-sponge technique appears to be an
      effective and simple method for closing an infected groin with preservation of
      the underlying prosthetic material.

PMID- 22617074
TI  - [Irritable bowel syndrome: from guideline to made-to-measure care?].
AB  - The new guideline on irritable bowel syndrome (IBS) advocates distinguishing IBS
      patients who predominantly suffer from constipation from those who mainly suffer
      from diarrhoea or from alternating bouts of diarrhoea and constipation. In the
      latter two groups, coeliac disease should be excluded, as should lactose
      intolerance if at all possible. Since there is no gold standard for the treatment
      of IBS a thorough explanation of the condition to patients is recommended.

PMID- 22617075
TI  - [Malignancy risk during TNF-blocking therapy increased or not?].
AB  - Tumour necrosis factor alpha (TNF) blockers were a major step forward in the
      treatment of patients with rheumatoid arthritis. In view of their
      immunosuppressive effects, concerns about enhancement of cancer development have
      arisen. So far there is no firm evidence that TNF-blockers increase the risk of
      solid tumours or lymphomas. However, it appears likely that TNF-blockers enhance
      the risk of non-melanoma skin cancer in patients with RA. Hence, it is
      recommended to screen patients treated with TNF-blockers periodically for skin
      cancer whereas routine screening for other malignancies is not useful.

PMID- 22617076
TI  - [The Dutch Cancer Society Cancer Risk Test].
AB  - The Dutch Cancer Society developed the 'KWF Kanker Risico Test' (Cancer Risk
      Test) to improve the information available to the Dutch population regarding
      cancer risk factors. This Internet test, based under licence on the American
      'Your Disease Risk' test, informs users about risk factors for 12 common types of
      cancer. The test provides an estimate of individual risk of a specific type of
      cancer and gives specific lifestyle advice that could lower that risk. This paper
      describes the development of the test, how it works, and its strengths and
      limitations.

PMID- 22617077
TI  - [A cancer risk test; who really needs it?].
AB  - In the Netherlands, people are getting tired of all the health promoting
      messages. Even so, a new cancer risk test has recently been introduced. The aim
      of this test is to increase knowledge of cancer risk factors and to achieve a
      change in lifestyle in order to decrease the incidence of cancer. However, people
      already know the most important risk factors and lifestyle change proves to be
      very difficult. It is unknown whether such a test will even reach the high risk
      groups and whether it will cause people to change their lives. Therefore, it is
      doubtful whether we really need this test.

PMID- 22617078
TI  - [Indicating risks in the Dutch Cancer Society Cancer Risk Test: indicating
      population risks improves risk perception].
AB  - OBJECTIVE: To have the Dutch Cancer Society Cancer Risk Test (KWF-KRT) assessed
      by users and to determine the effect of the numerical indication of risks on the
      perception of cancer risks. DESIGN: Cross-sectional questionnaire study. METHOD:
      In total 612 persons from the general population were given a shortened test
      version of the KWF-KRT test for colon and lung cancer via the Internet. 12
      different versions were tested, differing in the quantification of risks. Each
      participant received one version of the test for colon cancer and one for lung
      cancer. Before and after taking the KWF-KRT, participants were asked to complete
      a questionnaire. RESULTS: Completing the KWF-KRT version without numbers improved
      the understanding of the relative risk of colon cancer. Beforehand, 57% of the
      participants underestimated their personal cancer risk for colon cancer and 38%
      their risk for lung cancer. Addition of quantitative information on the
      population risk to the standard test resulted in twice as many correct estimates
      of the population risk and significantly improved the estimates of personal risk.
      It made no difference whether the population risk was presented only in numbers
      or also as a population diagram. The quantification of the personal risk and risk
      reduction had no effect. Approximately 12% of the participants indicated that
      they had become more worried about the risk of cancer after completing the test.
      The assessment of the KWF-KRT by the participants was largely positive.
      CONCLUSION: Adding quantitative information about the population risk led to a
      better understanding of both the population risk and the personal risk of cancer.

PMID- 22617079
TI  - Cognitive or psychodynamic therapy?

PMID- 22617080
TI  - Factor structure and convergent validity of the inventory of interpersonal
      problems in an inpatient setting.
AB  - The Inventory of Interpersonal Problems (IIP32) is a self-report measure designed
      to be used in clinical settings to assess interpersonal difficulties. However, it
      has been exclusively used in either outpatient or non-clinical settings, and
      psychometric data concerning its use in inpatients are limited. The current study
      examined the factor structure and construct validity of the IIP-32, and ways to
      optimally use this measure with inpatients at a private hospital providing
      intensive treatment. The original eight-factor structure was a poor fit to the
      data, whereas a five-factor structure provided a somewhat better fit. Although
      the five factors (Nonassertive, Detached, Intrusive, Self-Sacrificing, and
      Socially Inhibited) demonstrated adequate internal consistency, reliability, and
      limited convergent validity, the IIP is ultimately useful insofar as it engages
      patients in collaborative self-awareness during intensive psychotherapeutically
      oriented treatment.

PMID- 22617081
TI  - Adult attachment in the clinical management of borderline personality disorder.
AB  - Borderline personality disorder (BPD) is a common psychiatric disorder associated
      with severe functional impairment, high rates of suicide and comorbid psychiatric
      illness, intensive use of treatment, and high costs to society. The etiology and
      pathogenesis of BPD are still uncertain, although an interaction between
      biological and psychosocial factors has been proposed to explain how the
      condition develops. Attachment disturbances represent one of the developmental
      risk factors that have been most consistently found to be associated with BPD,
      with a number of studies reporting a significant strong association between
      insecure attachment and BPD, notwithstanding the variety of measures and
      attachment types employed in these studies. In this article, the author first
      reviews clinical descriptions and research findings concerning the association
      between attachment disturbances and BPD and then discusses how attachment theory
      may help clinicians who work with patients with BPD better understand the
      psychopathology of the illness and plan treatment.

PMID- 22617082
TI  - Treatment duration and premature termination of psychotherapy in personality
      disorders:  predictive performance of psychodynamic personality functioning.
AB  - OBJECTIVE: Little is known about predictors of treatment duration and premature
      termination of psychotherapy. METHOD: Sociodemographic variables, descriptive DSM
      IV psychiatric diagnoses, general symptom severity, and psychodynamic personality
      functioning were assessed in 148 inpatients with personality disorders who were
      receiving psychotherapy. Psychodynamic personality functioning was assessed using
      the Developmental Profile (DP). Predictive performance and incremental value over
      and beyond demographics and descriptive diagnoses were determined. RESULTS: In
      contrast to DSM-IV diagnoses and symptom severity, psychodynamic variables and
      the level of personality functioning significantly predicted treatment duration
      and premature treatment termination. Longer treatment duration was predicted by
      adaptive DP levels of personality functioning, whereas shorter treatment duration
      was associated with maladaptive personality functioning (primitive DP levels,
      including fragmentation and self-centeredness). DP variables independently
      explained 6% of the variance. CONCLUSION: In contrast to DSM-IV diagnoses and
      general symptom severity, psychodynamic personality variables significantly
      predicted treatment duration and premature discharge. These findings support the
      relevance of psycho-dynamic assessments in clinical practice, the DSM-5 proposals
      for the definition of personality functioning, and the predictive validity of the
      DP.

PMID- 22617083
TI  - Does age moderate the effect of personality disorder on coping style in
      psychiatric inpatients?
AB  - OBJECTIVE: To examine age-related differences in the relationship between
      personality and coping strategies in an Australian population of psychiatric
      inpatients. METHOD: Consenting eligible adults (N=238) from 18-100 years of age
      consecutively admitted to inpatient psychiatry units were assessed using the SCID
      I and II, the Coping Orientations to Problems Experienced Scale (COPE), the Brief
      Psychiatric Rating Scale (BPRS), the Global Assessment of Functioning Scale
      (GAF), the Social and Occupational Functioning Assessment Scale (SOFAS), the 12
      Item Short-Form Heath Survey (SF12), the Sarason Social Support Questionnaire,
      and the NEO Five Factor Inventory (NEO-FFI) (cognitively impaired, and non
      English speaking patients were excluded). RESULTS: Older adults reported less
      symptomatology than younger patients and younger patients described more
      personality dysfunction than older patients. As assessed by the COPE, older
      adults reported lower levels of dysfunctional coping strategies than younger
      adults. Personality traits, social supports, gender, and age predicted coping
      strategies, while Axis I diagnosis, education, personality disorder, and symptom
      severity were not significant predictors of coping strategies. CONCLUSION: This
      study found that influences on coping were multifactorial and moderated by age.
      These factors have implications for interventions designed to enhance coping
      strategies.

PMID- 22617084
TI  - Clinically important differences in the pharmacokinetics of the ten newer
      "atypical" antipsychotics:  part 1.
AB  - The "atypical" antipsychotics are grouped together by what they are not (i.e.,
      not dopamine-2 selective antagonists like haloperidol). While sharing that
      characteristic, these agents differ substantially in pharmacokinetics and
      pharmacodynamics. This column, the first in a series on these agents, reviews the
      bioavailability and half-life of the 10 newer "atypical" antipsychotics,
      including the most recently marketed members of this class (asenapine,
      iloperidone, and lurasidone). Drugs with high oral bioavailability are generally
      less susceptible to diet or drug-drug interactions affecting first pass
      metabolism. The converse is true for drugs with lower oral bioavailability (e.g.,
      they may have a food effect in which oral bioavailability is decreased in the
      fasted versus fed state). The half-life of an antipsychotic agent in large
      measure determines whether it can be safely and effectively administered once a
      day, at least in an immediate release formulation. Pharmacokinetic differences
      among atypical antipsychotics can explain why some individuals may not respond to
      the usually effective dose of a drug, while others may be especially sensitive to
      its dose-dependent adverse effects. An understanding of pharmacokinetic
      differences among the atypical antipsychotics can help clinicians optimize drug
      selection and dose for specific patients under specific treatment conditions.
      Subsequent columns in this series on atypical antipsychotics will discuss their
      metabolism, including the principal enzyme(s) mediating each drug's clearance,
      effects of co-administration of substantial CYP enzyme inhibitors, effect of
      hepatic and renal impairment, and the substantial and clinically important
      pharmacodynamic differences among these agents.

PMID- 22617085
TI  - Psychotherapy in the new paradigms for psychiatry.
AB  - Psychiatry is confronting challenges to create sweeping new paradigms for itself.
      The author contends that the psychosocial knowledge and psychotherapeutic skills
      of the psychiatrist must be integral to those paradigms. Abandoning crude,
      descriptive diagnostic categories in favor of discrete, dimensional measures that
      personalize selective neurobiological treatment for each individual is part of
      one proposed paradigm-but psychotherapy, especially psychodynamic therapies, have
      provided personalized therapy for over a century, using nature's own resources
      (human relationships and communication) to modulate the patient's unique, fixed
      patterns of thought, emotion, and behavior regardless of DSM diagnosis.
      Similarly, beyond the genetic core, the role of development and experience in
      shaping mental health and illness includes both neurobiological and interpersonal
      processes that dynamically modulate neural networks and their mental
      epiphenomena. Psychosocial interventions, using natural pathways, are vital for
      both prevention and treatment. Another proposed paradigm embraces closer
      coordination of psychiatric services with primary care in organized systems,
      which would probably include non-medical psychotherapists as well. Psychiatrists
      cannot effectively oversee, supervise, partner, or consult with other physicians
      or therapists if they have no psychotherapeutic awareness. Even when the primary
      mode of treatment is biological, skilled handling of the doctor-patient
      relationship is vital to adherence, to helping the patient manage his or her
      personal life, and even to effectiveness of medication at recommended doses.
      There is no substitute for instruction and extensive first-hand experience in
      learning to conduct psychotherapy or psychologically informed patient care. In a
      psychiatric residency curriculum that is likely to contain greatly increased
      attention to clinical neuroscience, time for the psyche must be preserved. The
      new paradigm might require a lengthened residency or additional fellowship years,
      which must include appropriate attention to psychosocial learning and
      psychotherapeutic expertise.

PMID- 22617086
TI  - Law and psychiatry. Doing forensic work, II: fees, billing, and collections.
AB  - Forensic practice fees, billing, and collection procedures are quite different
      from those in general psychiatry. Most forensic practices have far fewer
      "clients," and individual bills are usually larger. Collections are usually
      better (and less frequently discounted) in forensic practice, and resolving
      billing disputes is far more straightforward. Medicare, Medicaid, other insurance
      coverage, provider networks and agreements, procedure codes, and diagnosis
      related groups (DRGs) are all largely irrelevant in forensic work (although
      sometimes important to direct clinical services in correctional psychiatry or
      forensic treatment clinics). An understanding of the practicalities and ethics of
      charging and billing for forensic services greatly simplifies practice
      management.

PMID- 22617087
TI  - Clinical and ethical dilemmas in the psychiatric care of patients who border on
      the edge of being able to live safely and independently.
AB  - In the current economic environment and era of health care finance reform, mental
      health budgets have faced cutbacks across the nation, and they may face even
      deeper reductions in the future. Diminished funding for care of patients with
      severe psychiatric illness creates significant ethical and clinical dilemmas.
      Throughout medicine, physicians' professional virtues and obligations of
      beneficence may conflict with the need to balance respect for patient autonomy
      and deliver clinically appropriate, humane, and ethical care within a limited
      budget. This article uses a case presentation to highlight this struggle at the
      interface of psychiatry, ethics, and the emergency room in the care of people
      with severe mental illness.

PMID- 22617088
TI  - Inevitable suicide:  a new paradigm in psychiatry.
AB  - The author suggests that a new paradigm may be needed which holds that some
      suicides may be inevitable. The goal of this paradigm would be to diminish the
      sense of failure and inadequacy felt by many psychiatrists who experience the
      suicide of a patient and to increase understanding of the unique biopsychosocial
      profile of those whose suicides appear to be inevitable. The author stresses that
      this proposed paradigm should not be misconstrued as therapeutic nihilism but
      rather should serve to stimulate efforts to treat this patient population more
      effectively. Risk factors that place individuals at high risk for suicide are
      reviewed, including presence of a mental illness, genetic predisposition, and
      factors such as a history of abuse, divorce, unemployment, male gender, recent
      discharge from a psychiatric hospital, prior suicide attempts, alcohol or other
      substance abuse, a history of panic attacks, and persistent suicidal thoughts,
      especially if coupled with a plan. The author notes that, in those suicides that
      appear to have been inevitable, risk factors are not only numerous but at the
      extreme end of profound pathology. The example of Ernest Hemingway is used to
      illustrate how such a combination of risk factors may have contributed to his
      eventual suicide. Psychiatrists, like other doctors, may have to acknowledge that
      some psychiatric disorders are associated with a high mortality rate as a natural
      outcome. This could lead to heightened vigilance, a more realistic view of what
      can and cannot be achieved with therapy, and efforts to improve the quality of
      life of patients at high risk for suicide with the goal of reducing this risk and
      prolonging their lives. (Journal of Psychiatric Practice 2012;18:221-224).

PMID- 22617089
TI  - The role of liver transplantation for congenital extrahepatic portosystemic
      shunt.
AB  - BACKGROUND: Congenital extrahepatic portosystemic shunt (CEPS) is reported more
      frequently because of advances in imaging techniques. Liver transplantation (LT)
      is a therapeutic option, although the indications for LT are still controversial.
      METHODS: This study reviewed 34 cases of LT for CEPS, including 30 cases reported
      in the English medical literature and the patients treated in our department, to
      collect the clinical data associated with LT. RESULTS: The median age at
      diagnosis and LT was 3.7 and 6.8 years, respectively. Hepatic encephalopathy,
      including persistent hyperammonemia, was the most common indication of LT.
      Pulmonary complications, including hepatopulmonary syndrome and pulmonary
      hypertension, were the second most common indications of LT, and those patients
      underwent LT soon after the diagnosis. Although a shunt directly draining into
      the inferior vena cava was the most common type and managed by a simple direct
      anastomosis of the portal vein at LT, some cases required the modification of the
      portal vein reconstruction, such as interposition. Thirty patients were alive
      with a median follow-up period of 18 months. CONCLUSIONS: LT for CEPS showed an
      excellent outcome. The development of pulmonary complications is an early
      indication for LT. Precise planning of portal vein reconstruction is required
      before LT.

PMID- 22617091
TI  - Three cases of suspected sugammadex-induced hypersensitivity reactions.
AB  - Neuromuscular blocking agents have been implicated in 60-70% of anaphylactic
      events associated with anaesthesia. We report two cases of probable
      hypersensitivity reaction to sugammadex and an additional suspected but less
      supported case of possible immune-mediated reaction or other adverse reaction.
      The patients were given a bolus of sugammadex 100 mg immediately before
      extubation. In all three patients, a possible allergic reaction was suspected
      within 4 min of sugammadex administration, but with different degrees of
      severity. Skin testing was positive in two of these patients. Hypersensitivity to
      sugammadex unaccompanied by cardiovascular or respiratory symptoms might be
      missed during the course of anaesthesia. Careful monitoring for possible allergic
      responses is required in patients who have received sugammadex.

PMID- 22617090
TI  - Transfusion rate for 500 consecutive liver transplantations: experience of one
      liver transplantation center.
AB  - BACKGROUND: Orthotopic liver transplantation (OLT) has been associated with major
      blood loss and the need for blood product transfusions. During the last decade,
      improved surgical and anesthetic management has reduced intraoperative blood loss
      and blood product transfusions. A first report from our group published in 2005
      described a mean intraoperative transfusion rate of 0.3 red blood cell (RBC) unit
      per patient for 61 consecutive OLTs. Of these patients, 80.3% did not receive any
      blood product. The interventions leading to those results were a combination of
      fluid restriction, phlebotomy, liberal use of vasopressor medications, and
      avoidance of preemptive transfusions of fresh frozen plasma. This is a follow-up
      observational study, covering 500 consecutive OLTs. METHODS: Five hundred
      consecutive OLTs were studied. The transfusion rate of the first 61 OLTs was
      compared with the last 439 OLTs. Furthermore, multivariate logistic regression
      was used to determine the main predictors of intraoperative blood transfusion.
      RESULTS: A mean (SD) of 0.5 (1.3) RBC unit was transfused per patient for the 500
      OLTs, and 79.6% of them did not receive any blood product. There was no
      intergroup difference except for the final hemoglobin (Hb) value, which was
      higher for the last 439 OLTs compared with the previously reported smaller study
      (94 [20] vs. 87 [20] g/L). Two variables, starting Hb value and phlebotomy,
      correlated with OLT without transfusion. CONCLUSIONS: In our center, a low
      intraoperative transfusion rate could be maintained throughout 500 consecutive
      OLTs. Bleeding did not correlate with the severity of recipient's disease. The
      starting Hb value showed the strongest correlation with OLT without RBC
      transfusion.

PMID- 22617092
TI  - Elevated PEEP without effect upon gas embolism frequency or severity in
      experimental laparoscopic liver resection.
AB  - BACKGROUND: Carbon dioxide (CO(2)) embolism is a potential complication in
      laparoscopic liver surgery. Gas embolism (GE) is thought to occur when central
      venous pressure (CVP) is lower than the intra-abdominal pressure (IAP). This
      study aimed to investigate whether an increased CVP due to induction of PEEP
      could influence the frequency and severity of GE during laparoscopic liver
      resection. METHODS: Twenty anaesthetized piglets underwent laparoscopic left
      liver lobe resection and were randomly assigned to either 5 or 15 cm H(2)O PEEP
      (n=10 per group). During resection, a standardized injury to the left hepatic
      vein [venous cut (VC)] was created to increase the risk of GE. Haemodynamic and
      respiratory variables were monitored, and online arterial blood gas monitoring
      and transoesophageal echocardiography (TOE) were used. The occurrence and
      severity of embolism was graded as 0 (none), 1 (minor), or 2 (major), depending
      on the TOE results. RESULTS: No differences were found between the two groups
      regarding the frequency or severity of GE, during either the VC (P=0.65) or the
      rest of the surgery (P=0.24). GE occurred irrespective of the CVP-IAP gradient.
      CONCLUSIONS: Mechanisms other than the CVP-IAP gradient seemed during
      laparoscopic liver surgery to contribute to the formation of CO(2) embolism. This
      is of clinical importance to the anaesthetists.

PMID- 22617094
TI  - 75 years of mortality in the United States, 1935-2010.
AB  - While the overall risk of mortality decreased 60 percent over this 75-year
      period, there were fluctuations in the rate of decline most likely associated
      with changes in the broader environment. For example, the 29 percent decline in
      age-adjusted mortality in the earlier period from 1935 to 1954 was probably
      influenced by the introduction of various drugs such as antibiotics (2). In
      contrast, in the period 1955 to 1968, age-adjusted death rates decreased by only
      2 percent, influenced in part by increases in diseases linked to tobacco use such
      as cancer and chronic lower respiratory diseases (3,4). In the most recent period
      from 1969 to 2010, significant progress in the prevention, diagnosis, and
      treatment of cardiovascular diseases (5) likely contributed to the 41 percent
      decline in age-adjusted mortality despite cancer continuing to increase from 1969
      to 1990 and chronic lower respiratory diseases continuing to increase from 1969
      to 1998. Because year-to-year changes in death rates are often small, one might
      not appreciate the full extent of progress in reducing mortality in the United
      States over the past 3/4 of a century. For example, the 2010 age-adjusted death
      rate of 746.2 deaths per 100,000 population was just 0.5 percent lower than in
      2009. However, the 2010 rate represented a 60 percent decrease from the 1935 age
      adjusted death rate of 1,860.1 deaths per 100,000 population signaling
      significant progress in reducing the overall risk of death in the United States
      across all groups.

PMID- 22617093
TI  - Raised serum cardiac troponin I concentrations predict hospital mortality in
      intensive care unit patients.
AB  - BACKGROUND: Recent work suggests that increased plasma concentrations of cardiac
      troponin I (cTnI) are common in critically ill patients and are associated with
      poor outcome. We measured the frequency of increased plasma cTnI concentrations
      during patients' stay in a mixed medical/surgical intensive care unit (ICU) and
      compared our findings with hospital mortality. METHODS: Basic details, organ
      support, and hospital mortality were recorded for all patients treated in ICU
      during a 6 month period. cTnI concentrations were sampled daily for all patients,
      using 0.04 ug litre(-1) as the upper limit of normal, and 0.12 ug litre(-1) as an
      additional stratification point. RESULTS: Of 663 patients, 54% were male, with a
      mean (sd) age of 60 (18) yr, 65% were surgical patients, and the median Acute
      Physiology and Chronic Ill Health II (APACHE II) score was 15 (inter-quartile
      range 12-20). Increased cTnI concentrations were found in 345 patients (52%)
      while in ICU. One hundred and twenty patients (18%) died in hospital. cTnI
      concentration >0.04 ug litre(-1) was associated with reduced odds of hospital
      survival, independent of age, medical admission, unplanned admission, APACHE II
      score, mechanical ventilation, and haemofiltration (adjusted odds ratio 0.25, 95%
      confidence interval 0.08-0.75, P=0.014). Stratification by the degree of cTnI
      increase revealed an incremental trend towards a lower odds of hospital survival,
      including for patients with 'minor' elevations of cTnI (0.05-0.12 ug litre(-1)).
      CONCLUSIONS: Increased serum cTnI concentrations during ICU stay independently
      predicts hospital mortality, even when the threshold is low. We found a trend
      towards an association between 'minor' elevations in cTnI and higher in-hospital
      mortality.

PMID- 22617095
TI  - Prevalence of complex activity limitations among racial/ethnic groups and
      Hispanic subgroups of adults: United States, 2003-2009.
AB  - This brief has shown that racial and ethnic differences exist in the prevalence
      of complex activity limitations among adults. Further, within the U.S. Hispanic
      adult population, a number of significant differences were found in complex
      activity limitations among Mexican, Puerto Rican, Cuban, Central or South
      American, and other Hispanic adults-differences that would likely go unnoticed if
      the Hispanic population were treated as a single group. These disparities in the
      prevalence of complex activity limitations are further influenced by sex and age.

PMID- 22617096
TI  - Sacrifice: psychodynamic, cultural and clinical aspects.
AB  - Noting that the topic of sacrifice has remained largely unaddressed in
      psychoanalytic literature, the authors offer a discussion of it. Their
      elucidation of sacrifice opens with the definition and etymology of the word and
      moves on to the place of sacrifice in various religious traditions. They then
      summarize Freud's views on the topic and suggest that the subsequent analytic
      contributions have gone in three directions: the first extends and modifies
      Freud's proposal of triadic-hostile origins of sacrifice, the second locates such
      origins in dyadic and loving relations, and the third seeks to synthesize the
      foregoing trends. The authors then delineate the triad of altruism, masochism,
      and narcissism that underlie sacrifice. They propose that a spectrum of
      phenomena, ranging from healthy to pathological, is subsumed under the rubric of
      sacrifice. They also discuss the significance of such ideas to the conduct of
      psychotherapy and psychoanalysis.

PMID- 22617097
TI  - Loss of humanness: the ultimate trauma.
AB  - This paper is about chronic illness and its impact on the chronically ill and
      their loved ones who live through the illness and the eventual death. A new
      concept is introduced, the concept of "passing": physically ill people may pass
      as healthy even though they are physically ill. In addition to a discussion about
      why people choose to pass, two major paradoxes are considered. One concerns the
      paradox that results from "passing." The paradox is that while the falseness of
      "passing" keeps the self alive, it also deadens it before death. Specifically,
      "passing" enables the person with a physical illness to keep his well self alive
      with others, but results in one feeling dead, disconnected, detached, and
      inauthentic, before death. The second paradox involves the pressure on the
      chronically ill person to be heroically agentic in fighting the illness and
      overcoming it and, also, the pressure for this same person to be totally
      submissive and compliant with treatment. While in analytic treatment, the ill
      person can be helped to access authentic emotions and aliveness and to feel the
      power of authenticity.

PMID- 22617098
TI  - Destructive women and the men who can't leave them: pathological dependence or
      pathological omnipotence?
AB  - Clinicians have focused more on the troubling issue of women who are dominated
      and abused by men than they have on those occasions where men are abused by
      women. While usually not involving physical abuse, the destructiveness of some
      women, expressed in terms of harsh and destructive verbal and interpersonal
      behavior can be so striking and persistent that it should remain of interest to
      psychoanalysts. This clinical paper examines two examples of male patients who,
      while accomplished in many spheres of their lives, are nevertheless engaged in
      marriages to women whose hateful behavior toward them is impossible to deny.
      Despite considerable awareness of how much they are damaged by their wives, they
      are either unwilling or unable to utilize separation and divorce as tools to
      protect themselves, with the ultimate goal of starting life again free of the
      persecutory other. The dynamics involved for men stuck in such dyads are
      considered, including the possible negative role of a systems approach to
      couples' therapy that assumes mutual responsibility for the couples' dysfunction
      and distress.

PMID- 22617099
TI  - Psychosis: a synthesis of motivational and defect perspectives.
AB  - Based on the evolution of human intelligence and the tremendous cognitive
      capacities arising from it, we have an innate tendency for the extreme thought
      content, thought form, and sensory perceptions of psychosis. During the conscious
      and awake state, cognitive regulatory control processes block these more extreme
      variants to facilitate reality congruency necessary for adaptive functioning.
      While asleep there is no need for reality congruency and the cognitive regulatory
      control processes are deactivated allowing psychotic equivalents to be expressed
      in dreams. This paper helps synthesize the two dominant perspectives regarding
      the etiology of psychosis: the neuroscience defect perspective and the
      psychoanalytic motivational perspective. Regarding the former, defective
      cognitive regulation arising from certain conditions, such as the deficit state
      of schizophrenia, allows extreme cognitive distortions, thought form variants,
      and sensory perceptual experiences to intrude into the conscious and awake state,
      thereby producing psychosis. Consistent with the psychoanalytic motivational
      perspective, defensive processes can motivate extreme cognitive distortions,
      thought form variants and sensory perceptual experiences, and also facilitate
      their expression by deactivating the relevant cognitive regulatory control
      processes.

PMID- 22617100
TI  - Father and son: Freud revisits his Oedipus complex in Moses and Monotheism.
AB  - In this paper, I propose to understand Freud on his own terms and within his
      social, intellectual and psychological context. It is my hope that such an
      understanding will contribute in turn to our understanding of some of the sources
      of the creative process. Were it not for his fame, Freud's views on religion,
      history and art, would at best be but a footnote to these subjects. My contention
      is that Freud's writings on these subjects can contribute more to our
      understanding of Freud, the person, than they do to some of the subjects he is
      writing about. Toward this end I will focus on two of Freud's works, written more
      than 30 years apart, his early Moses of Michelangelo and his late-life work Moses
      and Monotheism, which reflect the considerable changes in Freud's thinking.

PMID- 22617101
TI  - The impact of maternal reflective functioning on children's reaction to 9/11: a
      comparison of two cases.

PMID- 22617102
TI  - Containing excess: sexuality, attachment and intersubjectivity in theory and
      transference.

PMID- 22617103
TI  - Revising the classical approach to dream interpretation.

PMID- 22617107
TI  - Antitumor activity of cell-permeable p18(INK4c) with enhanced membrane and tissue
      penetration.
AB  - Practical methods to deliver proteins systemically in animals have been hampered
      by poor tissue penetration and inefficient cytoplasmic localization of
      internalized proteins. We therefore pursued the development of improved
      macromolecule transduction domains (MTDs) and tested their ability to deliver
      therapeutically active p18(INK4c). MTD103 was identified from a screen of 1,500
      signal peptides; tested for the ability to promote protein uptake by cells and
      tissues; and analyzed with regard to the mechanism of protein uptake and the
      delivery of biologically active p18(INK4c) into cancer cells. The therapeutic
      potential of cell-permeable MTD103p18(INK4c) (CP-p18(INK4c)) was tested in the
      HCT116 tumor xenograft model. MTD103p18(INK4c) appeared to traverse plasma
      membranes directly, was transferred from cell-to-cell and was therapeutically
      effective against cancer xenografts, inhibiting tumor growth by 86-98% after 5
      weeks (P < 0.05). The therapeutic responses to CP-p18(INK4c) were accompanied by
      high levels of apoptosis in tumor cells. In addition to enhancing systemic
      delivery of CP-p18(INK4c) to normal tissues and cancer xenografts, the MTD103
      sequence delayed protein clearance from the blood, liver and spleen. These
      results demonstrate that macromolecule intracellular transduction technology
      (MITT), enabled by MTDs, may provide novel protein therapies against cancer and
      other diseases.

PMID- 22617111
TI  - Production of hydrogen from ethanol: review of reaction mechanism and catalyst
      deactivation.

PMID- 22617109
TI  - Lentiviral vectors displaying modified measles virus gp overcome pre-existing
      immunity in in vivo-like transduction of human T and B cells.
AB  - Gene transfer into quiescent T and B cells is important for gene therapy and
      immunotherapy approaches. Previously, we generated lentiviral vectors (LVs)
      pseudotyped with Edmonston (Ed) measles virus (MV) hemagglutinin (H) and fusion
      (F) glycoproteins (H/F-LVs), which allowed efficient transduction of quiescent
      human T and B cells. However, a major obstacle in the use of H/F-LVs in vivo is
      that most of the human population is vaccinated against measles. As the MV
      humoral immune response is exclusively directed against the H protein of MV, we
      mutated the two dominant epitopes in H, Noose, and NE. LVs pseudotyped with these
      mutant H-glycoproteins escaped inactivation by monoclonal antibodies (mAbs) but
      were still neutralized by human serum. Consequently, we took advantage of newly
      emerged MV-D genotypes that were less sensitive to MV vaccination due to a
      different glycosylation pattern. The mutation responsible was introduced into the
      H/F-LVs, already mutated for Noose and NE epitopes. We found that these mutant
      H/F-LVs could efficiently transduce quiescent lymphocytes in the presence of high
      concentrations of MV antibody-positive human serum. Finally, upon incubation with
      total blood, mimicking the in vivo situation, the mutant H/F-LVs escaped MV
      antibody neutralization, where the original H/F-LVs failed. Thus, these novel H/F
      LVs offer perspectives for in vivo lymphocyte-based gene therapy and
      immunotherapy.

PMID- 22617108
TI  - Inhibition of hepatitis C virus replication by intracellular delivery of multiple
      siRNAs by nanosomes.
AB  - Sustained antiviral responses of chronic hepatitis C virus (HCV) infection have
      improved recently by the use of direct-acting antiviral agents along with
      interferon (IFN)-alpha and ribavirin. However, the emergence of drug-resistant
      variants is expected to be a major problem. We describe here a novel
      combinatorial small interfering RNA (siRNA) nanosome-based antiviral approach to
      clear HCV infection. Multiple siRNAs targeted to the highly conserved 5'
      untranslated region (UTR) of the HCV genome were synthesized and encapsulated
      into lipid nanoparticles called nanosomes. We show that siRNA can be repeatedly
      delivered to 100% of cells in culture using nanosomes without toxicity. Six
      siRNAs dramatically reduced HCV replication in both the replicon and infectious
      cell culture model. Repeated treatments with two siRNAs were better than a single
      siRNA treatment in minimizing the development of an escape mutant, resulting in
      rapid inhibition of viral replication. Systemic administration of combinatorial
      siRNA-nanosomes is well tolerated in BALB/c mice without liver injury or
      histological toxicity. As a proof-of-principle, we showed that systemic
      injections of siRNA nanosomes significantly reduced HCV replication in a liver
      tumor-xenotransplant mouse model of HCV. Our results indicate that systemic
      delivery of combinatorial siRNA nanosomes can be used to minimize the development
      of escape mutants and inhibition of HCV infection.

PMID- 22617112
TI  - Design, aerodynamics and autonomy of the DelFly.
AB  - One of the major challenges in robotics is to develop a fly-like robot that can
      autonomously fly around in unknown environments. In this paper, we discuss the
      current state of the DelFly project, in which we follow a top-down approach to
      ever smaller and more autonomous ornithopters. The presented findings concerning
      the design, aerodynamics and autonomy of the DelFly illustrate some of the
      properties of the top-down approach, which allows the identification and
      resolution of issues that also play a role at smaller scales. A parametric
      variation of the wing stiffener layout produced a 5% more power-efficient wing.
      An experimental aerodynamic investigation revealed that this could be associated
      with an improved stiffness of the wing, while further providing evidence of the
      vortex development during the flap cycle. The presented experiments resulted in
      an improvement in the generated lift, allowing the inclusion of a yaw rate gyro,
      pressure sensor and microcontroller onboard the DelFly. The autonomy of the
      DelFly is expanded by achieving (1) an improved turning logic to obtain better
      vision-based obstacle avoidance performance in environments with varying texture
      and (2) successful onboard height control based on the pressure sensor.

PMID- 22617110
TI  - LNA-based oligonucleotide electrotransfer for miRNA inhibition.
AB  - Micro-RNAs (miRNAs) are small regulatory RNAs that play an important role in
      disease development and progression and therefore represent a potential new class
      of therapeutic targets. However, an effective and safe clinical approach for
      miRNA inhibition remains elusive, primarily due to the lack of effective delivery
      methods. We proposed to inhibit miRNA by electrotransferring an antisense DNA
      oligomer containing locked nucleic acids (LNAs) (LNA/DNA oligomer). We observed
      that electropulsation (EP) led to a strong cellular uptake of LNA/DNA oligomer.
      The LNA/DNA oligomer electrotransfer mechanism and intracellular localization
      were visually investigated in real time at the single-cell level. Cyanine 5
      labeled oligonucleotide entered exclusively during pulse application on the side
      of the permeabilized cell membrane facing the cathode, driven by electrophoretic
      forces. Minutes after the electrotransfer, the LNA/DNA oligomer diffused into the
      nucleus. EP provided the anti-miRNA oligomer with immediate and direct access to
      its cytoplasmic mature miRNA target and/or its nuclear precursor miRNA target. We
      then demonstrated using a LNA/DNA oligomer anti-miR34a that LNA/DNA oligomer
      electrotransfer decreased the level of the miR34a target and induced its
      functional inhibition. Our findings show that using the electrotransfer technique
      for LNA-based oligonucleotide delivery is a promising therapeutic strategy to
      silence deleterious miRNAs overexpressed in diseases.

PMID- 22617113
TI  - Monte Carlo study of radial energy deposition from primary and secondary
      particles for narrow and large proton beamlet source models.
AB  - In spot-scanning intensity-modulated proton therapy, numerous unmodulated proton
      beam spots are delivered over a target volume to produce a prescribed dose
      distribution. To accurately model field size-dependent output factors for beam
      spots, the energy deposition at positions radial to the central axis of the beam
      must be characterized. In this study, we determined the difference in the central
      axis dose for spot-scanned fields that results from secondary particle doses by
      investigating energy deposition radial to the proton beam central axis resulting
      from primary protons and secondary particles for mathematical point source and
      distributed source models. The largest difference in the central axis dose from
      secondary particles resulting from the use of a mathematical point source and a
      distributed source model was approximately 0.43%. Thus, we conclude that the
      central axis dose for a spot-scanned field is effectively independent of the
      source model used to calculate the secondary particle dose.

PMID- 22617114
TI  - Understanding racial and ethnic disparities in U.S. infant mortality rates.
AB  - In the United States, different racial and ethnic groups have very different
      infant mortality patterns. When assessing the relative contribution of the
      percentage of preterm births and gestational age-specific infant mortality rates
      to racial and ethnic infant mortality differences, we found that for non-Hispanic
      black women, 78 percent of their elevated infant mortality rate compared with non
      Hispanic white women was due to their higher percentage of preterm births, while
      22 percent was due to higher gestational age-specific infant mortality rates
      (primarily at 34 weeks of gestation or more). For Puerto Rican women, their
      elevated infant mortality rate compared with non-Hispanic white women was
      entirely due to their higher percentage of preterm births. However, AIAN women
      had a very different infant mortality pattern: 76 percent of their higher infant
      mortality rate compared with non-Hispanic white women was due to their higher
      gestational age-specific infant mortality rates (primarily at 34 weeks or more),
      and only 24 percent was due to their higher percentage of preterm births.These
      findings are consistent with the cause-of-death analysis, which found that for
      bothnon-Hispanic black and Puerto Rican women, most of their higher infant
      mortality rate compared with non-Hispanic white women was due to preterm-related
      causes. In contrast, for AIAN women, the infant mortality rate from SIDS was 2.4
      times, and the rate from unintentional injuries was 2.3 times, the non-Hispanic
      white rate. Infant mortality rates for non-Hispanic black women would be reduced
      by 71 percent, those for AIAN women by 64 percent, and those for Puerto Rican
      women by 67 percent if rates from preterm-related causes, congenital
      malformations, SIDS, and unintentional injuries could be reduced to non-Hispanic
      white levels.The different infant mortality patterns for non-Hispanic black,
      Puerto Rican, and AIAN women suggest different prevention strategies (6,7). In
      addition, because the percentage of preterm births for all U.S. racial and ethnic
      groups is higher than in other developed countries, all U.S. racial and ethnic
      groups might benefit from prematurity prevention efforts (8,9).

PMID- 22617115
TI  - Birth rates for U.S. teenagers reach historic lows for all age and ethnic groups.
AB  - The widespread significant declines in teen childbearing that began after 1991
      have strengthened in recent years. The teen birth rate dropped 17 percent from
      2007 through 2010, a record low, and 44 percent from 1991. Rates fell across all
      teen age groups, racial and ethnic groups, and nearly all states. The drop in the
      U.S. rate has importantly affected the number of births to teenagers. If the 1991
      rates had prevailed through the years 1992-2010, there would have been an
      estimated 3.4 million additional births to teenagers during that period. The
      impact of strong pregnancy prevention messages directed to teenagers has been
      credited with the birth rate declines (9-11). Recently released data from the
      National Survey of Family Growth, conducted by the Centers for Disease Control
      and Prevention's (CDC) National Center for Health Statistics (NCHS), have shown
      increased use of contraception at first initiation of sex and use of dual methods
      of contraception (that is, condoms and hormonal methods) among sexually active
      female and male teenagers. These trends may have contributed to the recent birth
      rate declines (12).

PMID- 22617116
TI  - Mathematical model of zinc absorption: effects of dietary calcium, protein and
      iron on zinc absorption.
AB  - A previously described mathematical model of Zn absorption as a function of total
      daily dietary Zn and phytate was fitted to data from studies in which dietary Ca,
      Fe and protein were also measured. An analysis of regression residuals indicated
      statistically significant positive relationships between the residuals and Ca, Fe
      and protein, suggesting that the presence of any of these dietary components
      enhances Zn absorption. Based on the hypotheses that (1) Ca and Fe both promote
      Zn absorption by binding with phytate and thereby making it unavailable for
      binding Zn and (2) protein enhances the availability of Zn for transporter
      binding, the model was modified to incorporate these effects. The new model of Zn
      absorption as a function of dietary Zn, phytate, Ca, Fe and protein was then
      fitted to the data. The proportion of variation in absorbed Zn explained by the
      new model was 0.88, an increase from 0.82 with the original model. A reduced
      version of the model without Fe produced an equally good fit to the data and an
      improved value for the model selection criterion, demonstrating that when dietary
      Ca and protein are controlled for, there is no evidence that dietary Fe
      influences Zn absorption. Regression residuals and testing with additional data
      supported the validity of the new model. It was concluded that dietary Ca and
      protein modestly enhanced Zn absorption and Fe had no statistically discernable
      effect. Furthermore, the model provides a meaningful foundation for efforts to
      model nutrient interactions in mineral absorption. 

PMID- 22617117
TI  - Effect of patient education in the management of coronary heart disease: a
      systematic review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: To assess the effects of patient education on mortality, morbidity,
      health-related quality of life (HRQoL), and healthcare costs in people with
      coronary heart disease (CHD). DESIGN: Systematic review and meta-analysis.
      METHODS: Data sources were Cochrane Library, Medline, Embase, PsycINFO, CINAHL,
      and ongoing trial registries until August 2010. We also checked study references.
      The study selection was based on design (randomized controlled trials with follow
      up of at least 6 months, published from 1990 onwards), population (adults with
      CHD), intervention (patient education stated to be the primary intervention), and
      comparators (usual care or no educational intervention). RESULTS: Thirteen
      studies (68,556 people with CHD) were included. Educational interventions ranged
      from two visits to a 4-week residential stay with 11 months of reinforcement
      sessions. Compared to no educational intervention, there was weak evidence that
      education reduced all-cause mortality (pooled relative risk (RR) 0.79, 95% CI
      0.55 to 1.13) and cardiac morbidity outcomes: myocardial infarction (pooled RR
      0.63, 95% CI 0.26 to 1.48), revascularization (pooled RR 0.58, 95% CI 0.19 to
      1.71), and hospitalization (pooled RR 0.83, 95% CI 0.65 to 1.07) at median 18
      months follow up. There was evidence to suggest that education can improve HRQoL
      and decrease healthcare costs by reductions in downstream healthcare utilization.
      CONCLUSIONS: Our review had insufficient power to exclude clinically important
      effects of education on mortality and morbidity. Nevertheless it supports the
      practice of CHD secondary prevention and rehabilitation programmes including
      education as an intervention. Further research is needed to determine the most
      effective and cost-effective format, duration, timing, and methods of education
      delivery.

PMID- 22617119
TI  - Clinical usefulness of carotid ultrasound to improve stroke risk assessment: ten
      year results from the Carotid Atherosclerosis Progression Study (CAPS).
AB  - BACKGROUND AND PURPOSE: To prevent strokes it is essential to correctly classify
      people according to their risk of stroke. The aim of the present study was to
      assess whether carotid ultrasound improves the stroke risk prediction in
      asymptomatic individuals. METHODS: The baseline visit of the Carotid
      Atherosclerosis Progression Study (CAPS) included assessment of conventional risk
      factors and carotid ultrasound. During the 10-year follow-up of 4995 subjects,
      strokes, transient ischaemic attacks (TIA) and deaths were recorded. We assessed
      the additional usefulness of carotid ultrasound compared to the Framingham Stroke
      Risk Score (FSRS) with reclassification statistics using four risk categories.
      RESULTS: Most risk models were not improved by carotid ultrasound. For individual
      stroke prediction, intima-media thickness (IMT) or plaque of the internal carotid
      arteries were more useful than common carotid or bifurcational IMT. The model
      predicting 'any stroke or death' was significantly improved when ultrasound
      parameters were included - 339 subjects (7.2%) were reclassified to another risk
      category (122 were shifted to a higher, 217 to a lower risk category); 182
      (53.7%) were correctly reclassified. The net reclassification improvement (NRI)
      was 7.7% (p = 0.029) and the integrated discrimination improvement (IDI) was
      0.73% (p = 0.023). CONCLUSIONS: When carotid ultrasound is not restricted to the
      common carotid artery but includes the internal carotid segments, the inclusion
      of ultrasound data into stroke risk models may improve the risk classification of
      individuals. Further validation in primary prevention cohorts is warranted.

PMID- 22617118
TI  - Socio-demographic variation in chest pain incidence and subsequent coronary heart
      disease in primary care in the United Kingdom.
AB  - BACKGROUND: We know little about socio-demographic differences in chest pain
      presenting to primary care and subsequent coronary heart disease (CHD) diagnosis.
      METHODS: We conducted a cohort study with 198,209 patients aged 30 years and over
      with a first episode of chest pain, using data from 339 general practices in The
      Health Improvement Network (THIN) primary care database during 1997-2007. We
      calculated incidence of chest pain and subsequent CHD by age, gender and
      quintiles of Townsend area deprivation score. RESULTS: Chest pain incidence was
      19.6/1000 person years at risk (PYAR, 95% CI 19.5-19.7). Incidence rose with age
      and increasing deprivation, with minimal gender differences. The incidence of CHD
      in the year following chest pain in primary care was 96.6/1000 PYAR (95% CI 95.1
      98.0). There were significant interactions with age/deprivation and
      gender/deprivation on subsequent CHD diagnosis. The effect of deprivation was
      less for those over 60 years, and greater for younger women. Women in their 30s
      with chest pain in deprived areas had 8.77 times (95% CI 3.34-23.06) the CHD
      incidence compared to those in the most affluent areas. The absolute risk
      difference was small (8/1000 PYAR, 95% CI 4.5-11.5/1000 PYAR). CONCLUSIONS: There
      was a modestly greater incidence of chest pain in primary care in more deprived
      areas compared to the least deprived areas. There were interactions between age,
      gender and deprivation on subsequent CHD diagnosis, with the greatest effect of
      deprivation on CHD diagnosis seen in younger women. This observation suggests the
      need for targeting health promotion and CHD prevention among younger women in
      deprived areas.

PMID- 22617120
TI  - High throughput single molecule tracking for analysis of rare populations and
      events.
AB  - High throughput single molecule tracking methods were developed to perform
      quantitative analyses of rare molecular populations. An optimization strategy for
      single molecule tracking at interfaces is described that allowed tracking of
      ~10(6) unique trajectories. These large statistical datasets were analyzed in
      order to identify and characterize distinct molecular populations based on their
      characteristic dynamic behavior (residence time or surface diffusion) and/or
      their spatial distribution. Cumulative (i.e. integrated) probability
      distributions were found to be several orders of magnitude more sensitive to rare
      populations than were raw probability distributions. Mapping using Accumulated
      Probe Trajectories (MAPT) was used to characterize molecular populations
      associated with rare surface heterogeneities. Importantly, large sample sizes
      were found to result in a dramatic enhancement in the ability to identify rare
      populations and to resolve their dynamic and spatial parameters.

PMID- 22617121
TI  - Differences in transcriptomic profiles of human cumulus cells isolated from
      oocytes at GV, MI and MII stages after in vivo and in vitro oocyte maturation.
AB  - BACKGROUND: Oocyte maturation and competence to development depends on its close
      relationship with cumulus cells (CCs). However, the maturation conditions of
      human cumulus-oocyte complexes (COCs) might affect gene expression in both oocyte
      and CCs. We thus compared the transcriptome profiles of CCs isolated from in vivo
      and in vitro matured COCs at different nuclear maturation stages. METHODS: Three
      groups of CCs from patients who underwent ICSI were included: CCs of patients
      with polycystic ovary syndrome (PCOS) referred for in vitro maturation (IVM), CCs
      from patients with PCOS for in vivo maturation (used as controls) and CCs from
      normal responders referred for in vivo maturation. CCs were isolated from COCs at
      the germinal vesicle, metaphase I and metaphase II stages. Microarray technology
      was used to analyse the global gene expression and significance analysis of
      microarray to compare the expression profiles of CCs from COCs at different
      nuclear maturation stages following IVM or in vivo maturation. Selected genes
      were validated by RT-qPCR. RESULTS: In CCs isolated after IVM, genes related to
      cumulus expansion and oocyte maturation, such as EREG, AREG and PTX3, were down
      regulated, while cell cycle-related genes were up-regulated in comparison with
      CCs from in vivo matured COCs from PCOS and normal responder patients. Moreover,
      irrespective of the stage of oocyte maturation, genes involved in DNA
      replication, recombination and repair were up-regulated in CCs after IVM.
      CONCLUSIONS: The CC transcriptomic signature varies according to both the oocyte
      maturation stage and the maturation conditions. Our findings suggest a delay in
      the acquisition of the mature CC phenotype following IVM, opening a new
      perspective for the improvement in IVM conditions.

PMID- 22617122
TI  - Ovarian reserve and response to IVF and in vitro maturation treatment following
      chemotherapy.
AB  - BACKGROUND: Chemotherapy and radiotherapy can result in ovarian failure and
      premature menopause. However, there is still a paucity of information on the
      ovarian reserve and efficacy of assisted reproduction treatment (ART) procedures
      in patients with cancer previously exposed to chemotherapy or radiotherapy. The
      aim of our study was to evaluate the ovarian reserve and ovarian response to IVF
      or in vitro maturation (IVM) treatment in women who had previously been treated
      with chemotherapy. METHODS: In this retrospective cohort study, we compared 23
      women with cancer who had undergone chemotherapy and subsequently underwent
      fertility treatment with IVF (n=14) or IVM (n=9). In the IVF group, patients
      mostly had hematologic, gynecologic, gastro-intestinal, bone and soft tissue
      cancers, whereas in the IVM group patients had estrogen-receptor positive breast
      cancer, hematologic and brain cancers. The control (unexposed) group consisted of
      70 age-matched women with male factor infertility undergoing the same treatment
      protocol (IVF n=42 and IVM n=28). All women were aged<42 years and undergoing
      their first cycle of ART. RESULTS: There were no differences in age and FSH
      levels between the cancer and the control groups. However, the antral follicle
      count (AFC) was lower in the cancer-IVF group (median: 5, range: 3-12) than in
      the control group (median: 15, range: 12-18; P=0.0009). Women with cancer treated
      with IVF had lower peak estradiol levels on the day of hCG administration than
      controls (P=0.006) and lower number of oocytes retrieved [median: 4.5, range: 2
      7; versus 12 (8-16) in controls; P<0.0001]. In patients with cancer treated with
      IVM, the AFC was lower than in the control group (median: 14, range: 9.5-17;
      versus median: 20.5 range: 16-23, respectively; P=0.0007). Likewise, the number
      of oocytes retrieved was lower in the cancer-IVM group (median: 6, range: 4-10)
      than that in the control group (median 10.5, range: 7.5-17; P=0.01). The
      percentage of mature metaphase II oocytes was comparable in the cancer and
      control groups. CONCLUSIONS: The ovarian reserve, response to gonadotrophins and
      number of oocytes retrieved are adversely affected by previous chemotherapy. This
      study reports the first series of IVM outcomes in cancer patients with a prior
      history of chemotherapy. In women with estrogen-receptor positive breast cancer,
      IVM of oocytes with cryopreservation of oocytes or embryos is a viable option.
      Since the efficacy of ART is significantly reduced after chemotherapy, early
      referral for fertility preservation before gonadotoxic treatment will give these
      young women the best chance to conceive.

PMID- 22617123
TI  - Alteration of gene expression in human cumulus cells as a potential indicator of
      oocyte aneuploidy.
AB  - BACKGROUND: Human female meiosis is particularly error prone, leading to the
      generation of aneuploidy, a problem which increases dramatically with advancing
      age. Despite being of great clinical importance, the genesis of oocyte aneuploidy
      remains poorly understood. Cumulus cells (CCs) surround oocytes in antral
      follicles and play a crucial role in regulating their maturation. During this
      investigation, we aimed to obtain an insight into the follicular environment of
      oocytes that become aneuploid and identify non-invasive markers of oocyte
      chromosome status and competence. METHODS: Microarray comparative genomic
      hybridization was used to assess oocyte ploidy. Expression of 96 genes was
      examined via a large real-time PCR experiment in 51 CC samples, whereas an
      additional 26 CC clumps were used for a more focused real-time PCR experiment
      assessing just three genes. Gene selection was based on the results of a previous
      microarray analysis comparing the transcriptome of CCs from normal and aneuploid
      oocytes. RESULTS: Fifty eight of the investigated genes were confirmed to be
      expressed in CCs. Patterns of expression were generally similar among all CC
      samples, regardless of the chromosomal status of the corresponding oocyte.
      However, two genes, SPSB2 and TP53I3, were both significantly down-regulated in
      CCs from chromosomally abnormal oocytes (P<0.05). The expression of SPSB2 was
      also found to display a strong trend towards up-regulation in the CCs of oocytes
      that produced a healthy live birth (P=0.054). CONCLUSIONS: In the current study,
      SPSB2 and TP53I3 exhibited highly significant differences in their expression
      between CCs of normal and chromosomally abnormal oocytes. SPSB2 is involved in
      intracellular signalling and homeostasis, whereas TP53I3 regulates carbohydrate
      metabolism and apoptosis. We speculate that both these genes might have the
      potential to serve as non-invasive markers of oocyte aneuploidy.

PMID- 22617124
TI  - The impact of the new Turkish regulation, imposing single embryo transfer after
      assisted reproduction technology, on neonatal intensive care unit utilization: a
      single center experience.
AB  - OBJECTIVES AND AIM: IVF has become an efficient and widely used treatment for
      infertile couples, however, it is responsible for an increasing number of
      multifetal pregnancies and adverse neonatal outcomes. This study aimed to assess
      a health service utilization in one neonatal intensive care unit (NICU), as a
      response to the 2010 Turkish reproductive regulation requiring single embryo
      transfer (SET). METHODS: All assisted reproductive technology (ART) pregnancies
      delivered at Zekai Tahir Burak Maternity Teaching Hospital between February 2010
      and October 2011 were included in this study. Subjects were divided into two
      groups: Group 1 consisted of infants conceived before the ART regulation, and
      born between February 2010 and October 2010, and Group 2 consisted of infants
      conceived after the ART regulation, and born between November 2010 and October
      2011. RESULTS: Upon comparing the study groups, we observed a significant
      decrease in the incidence of multiple births in Group 2. The mean gestational age
      and mean birthweight were significantly higher in Group 2. The rates of
      prematurity and low birthweight, very low birthweight and extremely low
      birthweight infants were significantly lower in Group 2. Similarly, the rates of
      NICU admission, respiratory distress syndrome, necrotizing enterocolitis anemia
      and pneumonia/sepsis, and the need for respiratory support (mechanical
      ventilation and nasal continuous positive airway pressure) were significantly
      lower in Group 2. CONCLUSIONS: According to our data, NICU utilization was
      reduced and the early post-natal outcomes of the babies were improved after the
      new Turkish regulation on ART imposing SET. However, multicenter studies are
      needed to generalize our results to the whole country.

PMID- 22617125
TI  - Intermediate and normal sized CGG repeat on the FMR1 gene does not negatively
      affect donor ovarian response.

PMID- 22617126
TI  - The risk of pancreatic cancer in symptomatic patients in primary care: a large
      case-control study using electronic records.
AB  - BACKGROUND: Over 8000 new pancreatic cancers are diagnosed annually in the UK;
      most at an advanced stage, with only 3% 5-year survival. We aimed to identify and
      quantify the risk of pancreatic cancer for features in primary care. METHODS: A
      case-control study using electronic primary care records identified and
      quantified the features of pancreatic cancer. Cases, aged >=40 in the General
      Practice Research Database, UK, with primary pancreatic cancer were matched with
      controls on age, sex and practice. Putative features of pancreatic cancer were
      identified in the year before diagnosis. Odds ratios (OR) were calculated for
      features of cancer using conditional logistic regression. Positive predictive
      values (PPV) were calculated for consulting patients. RESULTS: In all, 3635 cases
      and 16,459 controls were studied. Nine features were associated with pancreatic
      cancer (all P<0.001 except for back pain, P=0.004); jaundice, OR 1000 (95%
      confidence interval (CI) 4,302,500); abdominal pain, 5 (4.4, 5.6);
      nausea/vomiting, 4.5 (3.5, 5.7); back pain, 1.4 (1.1, 1.7); constipation, 2.2
      (1.7, 2.8); diarrhoea, 1.9 (1.5, 2.5); weight loss, 15 (11, 22); malaise, 2.4
      (1.6, 3.5); new-onset diabetes 2.1 (1.7, 2.5). Positive predictive values for
      patients aged >=60 were <1%, apart from jaundice at 22% (95% CI 14, 52), though
      several pairs of symptoms had PPVs >1%. CONCLUSION: Most previously reported
      symptoms of pancreatic cancer were also relevant in primary care. Although
      predictive values were small - apart from jaundice - they provide a basis for
      selection of patients for investigation, especially with multiple symptoms.

PMID- 22617128
TI  - Effect of (Neo)adjuvant zoledronic acid on disease-free and overall survival in
      clinical stage II/III breast cancer.
AB  - BACKGROUND: Despite neoadjuvant/adjuvant chemotherapy, women with resectable
      stage II/III breast cancer (BC) have high risk of recurrent disease. Recent data
      suggest that zoledronic acid (ZOL) therapy concurrent with adjuvant treatments
      may improve cancer-related outcomes in patients with BC. METHODS: Disease-free
      survival (DFS; secondary end point) and overall survival (OS; tertiary end point)
      were evaluated in 119 women with stage II/III BC randomised to intravenous ZOL 4
      mg every 3 weeks for 1 year or no ZOL (control) starting with the first
      chemotherapy cycle. RESULTS: At 61.9 months' median follow-up, there was no
      significant difference in recurrence or survival between study arms. However,
      time to recurrence or death (DFS) was significantly different between subgroups
      defined by oestrogen receptor (ER) status (interaction P=0.010 for DFS and 0.025
      for OS). Hazard ratios (HRs) for disease recurrence and death were significantly
      less among patients with ER-negative (ER(-)) tumours who received ZOL vs no ZOL
      (DFS: HR=0.361, 95% confidence interval (CI) 0.148, 0.880; OS: HR=0.375, 95% CI
      0.143, 0.985). CONCLUSION: ZOL administered with chemotherapy may improve DFS and
      OS in a subset of BC patients with ER(-) tumours. This study was not powered to
      compare subgroups of patients; thus, these findings should be considered
      hypothesis generating.

PMID- 22617127
TI  - KRAS mutations in primary tumours and post-FOLFOX metastatic lesions in cases of
      colorectal cancer.
AB  - BACKGROUND: KRAS mutations are predictive markers for the efficacy of anti-EGFR
      antibody therapies in patients with metastatic colorectal cancer. Although the
      mutational status of KRAS is reportedly highly concordant between primary and
      metastatic lesions, it is not yet clear whether genotoxic chemotherapies might
      induce additional mutations. METHODS: A total of 63 lesions (23 baseline primary,
      18 metastatic and 24 post-treatment metastatic) from 21 patients who were treated
      with FOLFOX as adjuvant therapy for stage III/IV colorectal cancer following
      curative resection were examined. The DNA samples were obtained from formalin
      fixed paraffin-embedded specimens, and KRAS, NRAS, BRAF and PIK3CA mutations were
      evaluated. RESULTS: The numbers of primary lesions with wild-type and mutant KRAS
      codons 12 and 13 were 8 and 13, respectively. The mutational status of KRAS
      remained concordant between the primary tumours and the post-FOLFOX metastatic
      lesions, irrespective of patient background, treatment duration and disease-free
      survival. Furthermore, the mutational statuses of the other genes evaluated were
      also concordant between the primary and metastatic lesions. CONCLUSION: Because
      the mutational statuses of predictive biomarker genes were not altered by FOLFOX
      therapy, specimens from both primary tumours and post-FOLFOX tumour metastases
      might serve as valid sources of DNA for known genomic biomarker testing.

PMID- 22617131
TI  - An anatomically driven anisotropic diffusion filtering method for 3D SPECT
      reconstruction.
AB  - In this study, we aim to reconstruct single-photon emission computed tomography
      images using anatomical information from magnetic resonance imaging as a priori
      knowledge about the activity distribution. The trade-off between anatomical and
      emission data is one of the main concerns for such studies. In this work, we
      propose an anatomically driven anisotropic diffusion filter (ADADF) as a
      penalized maximum likelihood expectation maximization optimization framework. The
      ADADF method has improved edge-preserving denoising characteristics compared to
      other smoothing penalty terms based on quadratic and non-quadratic functions. The
      proposed method has an important ability to retain information which is absent in
      the anatomy. To make our approach more stable to the noise-edge classification
      problem, robust statistics have been employed. Comparison of the ADADF method is
      performed with a successful anatomically driven technique, namely, the Bowsher
      prior (BP). Quantitative assessment using simulated and clinical neuroreceptor
      volumetric data show the advantage of the ADADF over the BP. For the modelled
      data, the overall image resolution, the contrast, the signal-to-noise ratio and
      the ability to preserve important features in the data are all improved by using
      the proposed method. For clinical data, the contrast in the region of interest is
      significantly improved using the ADADF compared to the BP, while successfully
      eliminating noise.

PMID- 22617129
TI  - Associations between hepatocyte growth factor, c-Met, and basic fibroblast growth
      factor and survival in endometrial cancer patients.
AB  - BACKGROUND: Hepatocyte growth factor (HGF), c-Met, and basic fibroblast growth
      factor (bFGF) are molecular markers that contribute to angiogenesis and
      proliferation in numerous cancers. We assessed the prognostic significance of
      these factors in tumour and stroma of endometrial cancer (EC) patients (n=211).
      METHODS: Immunohistochemistry (IHC) was used to detect tumour and stromal protein
      expression of the biomarkers. Associations between expression and
      clinicopathological factors were assessed using Chi-square tests. Kaplan-Meier
      curves, log-rank tests, and Cox regression were used to summarise associations
      between biomarker expression and overall survival (OS) and recurrence-free
      survival (RFS). RESULTS: Tumour bFGF was significantly associated with high-grade
      endometrioid and clear cell histology (P<0.001), advanced stage (P=0.008),
      positive lymph-node involvement (P=0.002), poor OS (log-rank test, P=0.009), and
      poor RFS (P<0.001). In multivariable analyses, cases with HGF-positive, stromal
      bFGF-positive tumours had a lower risk of death compared with cases with HGF
      positive, stromal bFGF-negative tumours (hazard ratio (HR): 0.14, 95% CI: 0.03,
      0.60). Cases with HGF-positive, bFGF-positive tumours had a higher risk of
      recurrence compared with cases with negative expression of both markers (HR:
      9.88, 95% CI: 2.63, 37.16). CONCLUSION: These IHC data show that tumour and
      stromal bFGF expression have opposite associations with survival outcomes in EC
      patients. If confirmed in larger studies, tumour-derived bFGF could be an
      attractive target in EC therapy.

PMID- 22617132
TI  - Soft robotic arm inspired by the octopus: I. From biological functions to
      artificial requirements.
AB  - Octopuses are molluscs that belong to the group Cephalopoda. They lack joints and
      rigid links, and as a result, their arms possess virtually limitless freedom of
      movement. These flexible appendages exhibit peculiar biomechanical features such
      as stiffness control, compliance, and high flexibility and dexterity. Studying
      the capabilities of the octopus arm is a complex task that presents a challenge
      for both biologists and roboticists, the latter of whom draw inspiration from the
      octopus in designing novel technologies within soft robotics. With this idea in
      mind, in this study, we used new, purposively developed methods of analysing the
      octopus arm in vivo to create new biologically inspired design concepts. Our
      measurements showed that the octopus arm can elongate by 70% in tandem with a 23%
      diameter reduction and exhibits an average pulling force of 40 N. The arm also
      exhibited a 20% mean shortening at a rate of 17.1 mm s(-1) and a longitudinal
      stiffening rate as high as 2 N (mm s)(-1). Using histology and ultrasounds, we
      investigated the functional morphology of the internal tissues, including the
      sinusoidal arrangement of the nerve cord and the local insertion points of the
      longitudinal and transverse muscle fibres. The resulting information was used to
      create novel design principles and specifications that can in turn be used in
      developing a new soft robotic arm.

PMID- 22617130
TI  - Phase II multi-institutional prospective randomised trial comparing S
      1+paclitaxel with S-1+cisplatin in patients with unresectable and/or recurrent
      advanced gastric cancer.
AB  - BACKGROUND: A combination of S-1 and cisplatin has been shown to be effective
      with acceptable safety for the first-line treatment of far-advanced gastric
      cancer in Japan. This is the first randomised phase II trial to compare S
      1+paclitaxel with S-1+cisplatin in this setting. METHODS: Patients with
      unresectable and/or recurrent advanced gastric cancer were randomly assigned to
      receive one of the two regimens: S-1 (40 mg m(-2) twice daily) on days 1-14 plus
      paclitaxel (60 mg m(-2)) on days 1, 8, and 15 of a 4-week cycle (S-1+paclitaxel)
      or S-1 (40 mg m(-2) twice daily) on days 1-21 plus cisplatin (60 mg m(-2)) on day
      8 of a 5-week cycle (S-1+cisplatin). The primary end point was the response rate
      (RR). Secondary end points included progression-free survival (PFS), overall
      survival (OS), and safety. RESULTS: A total of 83 patients were eligible for
      safety and efficacy analyses. In the S-1+paclitaxel and S-1+cisplatin groups, RRs
      (52.3% vs 48.7%; P=0.74) and median PFS (9 vs 6 months; P=0.50) were similar. The
      median OS was similar in the S-1+paclitaxel and S-1+cisplatin groups (16 vs 17
      months; P=0.84). The incidence of grade 3 or higher haematological toxicity was
      19.0% with S-1+paclitaxel and 19.5% with S-1+cisplatin. The incidence of grade 3
      or higher non-haematological toxicity was 14.2% with S-1+paclitaxel and 17.1%
      with S-1+cisplatin. CONCLUSION: S-1+paclitaxel was suggested to be a feasible and
      effective non-platinum-based regimen for chemotherapy in patients with advanced
      gastric cancer. Our results should be confirmed in multicenter, phase III
      controlled clinical trials.

PMID- 22617133
TI  - Cutaneous metastases from internal malignancies:  a clinicopathologic and
      immunohistochemical review.
AB  - Skin metastases occur in 0.6%-10.4% of all patients with cancer and represent 2%
      of all skin tumors. Skin metastases from visceral malignancies are important for
      dermatologists and dermatopathologists because of their variable clinical
      appearance and presentation, frequent delay and failure in their diagnosis,
      relative proportion of different internal malignancies metastasizing to the skin,
      and impact on morbidity, prognosis, and treatment. Another factor to take into
      account is that cutaneous metastasis may be the first sign of clinically silent
      visceral cancer. The relative frequencies of metastatic skin disease tend to
      correlate with the frequency of the different types of primary cancer in each
      sex. Thus, women with skin metastases have the following distribution in
      decreasing order of frequency of primary malignancies: breast, ovary, oral
      cavity, lung, and large intestine. In men, the distribution is as follows: lung,
      large intestine, oral cavity, kidney, breast, esophagus, pancreas, stomach, and
      liver. A wide morphologic spectrum of clinical appearances has been described in
      cutaneous metastases. This variable clinical morphology included nodules,
      papules, plaques, tumors, and ulcers. From a histopathologic point of view, there
      are 4 main morphologic patterns of cutaneous metastases involving the dermis,
      namely, nodular, infiltrative, diffuse, and intravascular. Generally, cutaneous
      metastases herald a poor prognosis. The average survival time of patients with
      skin metastases is a few months. In this article, we review the clinicopathologic
      and immunohistochemical characteristics of cutaneous metastases from internal
      malignancies, classify the most common cutaneous metastases, and identify studies
      that may assist in diagnosing the origin of a cutaneous metastasis.

PMID- 22617134
TI  - Eosinophilic cytoplasmic inclusion bodies in vesicular multinucleated
      melanocytes:  a clue to the diagnosis of benign melanocytic lesions.
AB  - Different types of multinucleated melanocytes have been described in benign and
      malignant melanocytic lesions. Here we describe a relatively common, though
      underappreciated, type of multinucleated melanocyte characterized by abundant
      vesicular and fibrillary-appearing cytoplasm containing one or multiple
      eosinophilic inclusion bodies. In our experience, these vesicular multinucleated
      melanocytes with inclusion bodies are invariably seen in nevi of long duration.
      The presence of these cells can be a reassuring histological finding when
      evaluating a melanocytic lesion.

PMID- 22617136
TI  - Plaque-like cutaneous mucinosis:  case report and literature review.
AB  - Midline mucinosis was observed in a 14-year-old man, which was confined to the
      midline of the back and appeared as asymptomatic, nonindurated, hyperpigmented
      plaques. Skin biopsies showed prominent interstitial mucinosis with perivascular
      lymphocytic infiltration. A literature review of plaque-like mucinosis revealed
      14 previous cases with this distinct presentation that may overlap with reticular
      erythematous mucinosis and connective tissue disease. Midline mucinosis has been
      previously reported in prepubertal children but is rare.

PMID- 22617137
TI  - Infectious disease prevalence in Los Angeles county--a comparison to national
      estimates, 1999-2004 birth rates for U.S. teenagers reach historic lows for all
      age and ethnic groups.
AB  - This is the first time seroprevalence of antibody to these nine infectious
      diseases have been available for LAC. Differences in the race and ethnicity
      distribution of the United States and LAC were observed. Because disease
      prevalence varies by race and ethnicity, in some instances these demographic
      differences affected the population differences seen between the United States
      and LAC in the seroprevalence of the infectious diseases reported in this study.
      Seroprevalence for HAV was higher in LAC as compared with the United States among
      the total population and among the Mexican-American population. California is 1
      of 11 states in which routine vaccination of children was recommended in 1999 by
      the Advisory Committee on Immunization Practices (ACIP) because mean incidence
      rates in these states were at least twice the national mean from 1987-1997 (9).
      Seroprevalence to CMV and T. gondii have been shown to be higher among Mexican
      American persons then other race and ethnicity groups (1,3). The higher
      seropositivity for CMV and T. gondii among persons from LAC is due to the higher
      proportion of Mexican-American persons in the LAC population. No differences in
      seropositivity were observed when comparing Mexican-American persons in the
      United States and LAC for these two outcomes. No significant differences in
      seroprevalence between the United States and LAC were seen for measles, mumps,
      rubella, varicella, HSV-1, and HSV-2. Estimates of seropositivity from
      immunization or disease for LAC may assist in policy development, program
      planning, and measuring health disparities.

PMID- 22617138
TI  - Ipomoea aquatica extract shows protective action against thioacetamide-induced
      hepatotoxicity.
AB  - In the Indian system of traditional medicine (Ayurveda) it is recommended to
      consume Ipomoea aquatica to mitigate disorders like jaundice. In this study, the
      protective effects of ethanol extract of I. aquatica against liver damage were
      evaluated in thioacetamide (TAA)-induced chronic hepatotoxicity in rats. There
      was no sign of toxicity in the acute toxicity study, in which Sprague-Dawley (SD)
      rats were orally fed with I. aquatica (250 and 500 mg/kg) for two months along
      with administration of TAA (i.p injection 200 mg/kg three times a week for two
      months). The results showed that the treatment of I. aquatica significantly
      lowered the TAA-induced serum levels of hepatic enzyme markers (ALP, ALT, AST,
      protein, albumin, bilirubin and prothrombin time). The hepatic content of
      activities and expressions SOD and CAT that were reduced by TAA were brought back
      to control levels by the plant extract supplement. Meanwhile, the rise in MDA
      level in the TAA receiving groups also were significantly reduced by I. aquatica
      treatment. Histopathology of hepatic tissues by H&E and Masson trichrome stains
      displayed that I. aquatica has reduced the incidence of liver lesions, including
      hepatic cells cloudy swelling, infiltration, hepatic necrosis, and fibrous
      connective tissue proliferation induced by TAA in rats. Therefore, the results of
      this study show that the protective effect of I. aquatica in TAA-induced liver
      damage might be contributed to its modulation on detoxification enzymes and its
      antioxidant and free radical scavenger effects. Moreover, it confirms a
      scientific basis for the traditional use of I. aquatica for the treatment of
      liver disorders.

PMID- 22617139
TI  - Low-fat milk consumption among children and adolescents in the United States,
      2007-2008.
AB  - In 2007-2008, among children and adolescents aged 2-19 years, 77.7% of boys and
      67.4% of girls reported daily consumption of milk. Fewer than 10% of children and
      adolescents reported never consuming milk over the preceding 30 days. Among
      children and adolescents who reported milk consumption, two-percent milk was
      reported as the usual type of milk consumed more often than other milk types.
      Only 20.2% of children and adolescents reported consuming low-fat milk as their
      usual type of milk; low-fat milk consumption was particularly low among non
      Hispanic black, Hispanic, and low-income children and adolescents. The overall
      low consumption of low-fat milk suggests the majority of children and adolescents
      do not adhere to recommendations by Dietary Guidelines for Americans, 2010 and
      the American Academy of Pediatrics for all children aged 2 years and over to
      drink low-fat milk. Recently, First Lady Michelle Obama's "Let's Move!" campaign
      (5) and "The Surgeon General's Vision for a Healthy and Fit Nation 2010" (6) have
      recommended promoting water and low-fat milk and reducing sugar-sweetened
      beverages as components of comprehensive obesity prevention strategies.

PMID- 22617141
TI  - A crypt-specific core microbiota resides in the mouse colon.
AB  - In an attempt to explore the microbial content of functionally critical niches of
      the mouse gastrointestinal tract, we targeted molecular microbial diagnostics of
      the crypts that contain the intestinal stem cells, which account for epithelial
      regeneration. As current evidence indicates, the gut microbiota affects
      epithelial regeneration; bacteria that are likely to primarily participate in
      this essential step of the gut, microbiota cross talk, have been identified. We
      show in this article that only the cecal and colonic crypts harbor resident
      microbiota in the mouse and that regardless of the line and breeding origin of
      these mice, this bacterial population is unexpectedly dominated by aerobic
      genera. Interestingly, this microbiota resembles the restricted microbiota found
      in the midgut of invertebrates; thus, the presence of our so-called "crypt
      specific core microbiota" (CSCM) in the mouse colon potentially reflects a
      coevolutionary process under selective conditions that can now be addressed. We
      suggest that CSCM could play both a protective and a homeostatic role within the
      colon. This article is setting the bases for such studies, particularly by
      providing a bona fide--and essentially cultivable--crypt microbiota of reference.
      IMPORTANCE: Metagenomic typing of the whole-gut luminal microbiome was recently
      provided, revealing great opportunities for physiological and physiopathological
      analysis of the host-microbiota interface. On this basis, it appears increasingly
      important to analyze which niches of the gut exposed to a particular microbiota
      are of major functional importance, specifically focusing on the crypt, which
      accounts for permanent epithelial renewal, and to analyze how this microbiota
      compares to its luminal counterpart in composition and quantity. Crypt-specific
      core microbiotas may show themselves as important elements regarding crypt
      protection and homeostasis of its functions.

PMID- 22617140
TI  - Comparative genomics of vancomycin-resistant Staphylococcus aureus strains and
      their positions within the clade most commonly associated with Methicillin
      resistant S. aureus hospital-acquired infection in the United States.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) strains are leading causes of
      hospital-acquired infections in the United States, and clonal cluster 5 (CC5) is
      the predominant lineage responsible for these infections. Since 2002, there have
      been 12 cases of vancomycin-resistant S. aureus (VRSA) infection in the United
      States-all CC5 strains. To understand this genetic background and what
      distinguishes it from other lineages, we generated and analyzed high-quality
      draft genome sequences for all available VRSA strains. Sequence comparisons show
      unambiguously that each strain independently acquired Tn1546 and that all VRSA
      strains last shared a common ancestor over 50 years ago, well before the
      occurrence of vancomycin resistance in this species. In contrast to existing
      hypotheses on what predisposes this lineage to acquire Tn1546, the barrier posed
      by restriction systems appears to be intact in most VRSA strains. However, VRSA
      (and other CC5) strains were found to possess a constellation of traits that
      appears to be optimized for proliferation in precisely the types of polymicrobic
      infection where transfer could occur. They lack a bacteriocin operon that would
      be predicted to limit the occurrence of non-CC5 strains in mixed infection and
      harbor a cluster of unique superantigens and lipoproteins to confound host
      immunity. A frameshift in dprA, which in other microbes influences uptake of
      foreign DNA, may also make this lineage conducive to foreign DNA acquisition.
      IMPORTANCE: Invasive methicillin-resistant Staphylococcus aureus (MRSA) infection
      now ranks among the leading causes of death in the United States. Vancomycin is a
      key last-line bactericidal drug for treating these infections. However, since
      2002, vancomycin resistance has entered this species. Of the now 12 cases of
      vancomycin-resistant S. aureus (VRSA), each was believed to represent a new
      acquisition of the vancomycin-resistant transposon Tn1546 from enterococcal
      donors. All acquisitions of Tn1546 so far have occurred in MRSA strains of the
      clonal cluster 5 genetic background, the most common hospital lineage causing
      hospital-acquired MRSA infection. To understand the nature of these strains, we
      determined and examined the nucleotide sequences of the genomes of all available
      VRSA. Genome comparison identified candidate features that position strains of
      this lineage well for acquiring resistance to antibiotics in mixed infection.

PMID- 22617143
TI  - Ginsenoside Rg1 prevents SK-N-SH neuroblastoma cell apoptosis induced by
      supernatant from Abeta1-40-stimulated THP-1 monocytes.
AB  - Excessive accumulation of amyloid-beta (Abeta) has been proposed as a pivotal
      event in Alzheimer's disease (AD) pathogenesis. Possible mechanisms underlying
      Abeta-induced neurotoxicity include inflammation and apoptosis. Here, the
      protective effect of ginsenoside Rg1 (GRg1) on neuronal damage was examined in an
      in vitro inflammatory neurodegeneration model. Supernatant from Abeta(1-40)
      stimulated THP-1 monocytes was added to SK-N-SH neuroblastoma cell culture
      medium. Incubation of SK-N-SH cells with cell-free supernatant from Abeta(1-40)
      (125nM)-treated THP-1 monocytes for 24 h significantly increased lactate
      dehydrogenase (LDH) release, cell apoptosis, Bax and caspase-3 expression in SK-N
      SH cells. However, pretreating THP-1 monocytes with GRg1 (50, 100 or 150 MUM) for
      30 min markedly reduced IL-1beta, IL-8 and TNF-alpha levels in Abeta(1-40)
      stimulated supernatant. LDH release, cell apoptosis, Bax and caspase-3 expression
      in SK-N-SH cells were significantly decreased when cultured with cell-free
      supernatant from Abeta(1-40)-stimulated THP-1 monocytes that were pretreated with
      GRg1. The results suggest that Abeta(1-40)-induced neuronal injury and apoptosis
      may be mediated by inflammatory monocyte reactions, and GRg1 exerts a protective
      effect against Abeta(1-40)-induced neuronal injury and apoptosis, likely through
      its anti-inflammatory mechanism.

PMID- 22617142
TI  - Three-way assessment of long-chain n-3 PUFA nutrition: by questionnaire and
      matched blood and skin samples.
AB  - The long-chain n-3 PUFA, EPA, is believed to be important for skin health,
      including roles in the modulation of inflammation and protection from
      photodamage. FFQ and blood levels are used as non-invasive proxies for assessing
      skin PUFA levels, but studies examining how well these proxies reflect target
      organ content are lacking. In seventy-eight healthy women (mean age 42.8, range
      21-60 years) residing in Greater Manchester, we performed a quantitative analysis
      of long-chain n-3 PUFA nutrition estimated from a self-reported FFQ (n 75) and
      correlated this with n-3 PUFA concentrations in erythrocytes (n 72) and dermis (n
      39). Linear associations between the three n-3 PUFA measurements were assessed by
      Spearman correlation coefficients and agreement between these measurements was
      estimated. Average total dietary content of the principal long-chain n-3 PUFA EPA
      and DHA was 171 (SD 168) and 236 (SD 248) mg/d, respectively. EPA showed
      significant correlations between FFQ assessments and both erythrocyte (r 0.57, P<
      0.0001) and dermal (r 0.33, P= 0.05) levels, as well as between erythrocytes and
      dermis (r 0.45, P= 0.008). FFQ intake of DHA and the sum of n-3 PUFA also
      correlated well with erythrocyte concentrations (r 0.50, P< 0.0001; r 0.27, P=
      0.03). Agreement between ranked thirds of dietary intake, blood and dermis
      approached 50% for EPA and DHA, though gross misclassification was lower for EPA.
      Thus, FFQ estimates and circulating levels of the dietary long-chain n-3 PUFA,
      EPA, may be utilised as well-correlated measures of its dermal bioavailability.

PMID- 22617144
TI  - Clusterin in neurological disorders: molecular perspectives and clinical
      relevance.
AB  - Firstly discovered in rete testis fluid, clusterin is a glycoprotein present in
      most of the other biological fluids. Several isoforms of clusterin are encoded
      from a single gene located on chromosome 8 in human species. Among the different
      isoforms, the secreted form of clusterin is expressed by a variety of tissues,
      including the nervous system under normal conditions. This form is presumed to
      play an anti-apoptotic role and seems to be a major determinant in cell survival
      and neuroplasticity after stroke. In animal models of this pathology, both
      neuronal and astroglial subpopulations express high levels of clusterin early
      after the ischemic damage. Recent lines of evidence point also to its possible
      involvement in neurodegenerative disorders. It is thought that in Alzheimer's
      disease the association between amyloidogenic peptides and clusterin contributes
      to limit Abeta species misfolding and facilitates their clearance from the
      extracellular space. Thus, intercellular and intracellular factors that modulate
      local clusterin expression in the nervous system may represent potent targets for
      neurodegenerative disease therapies. In this review we provide a critical
      overview of the most recent data on the involvement of clusterin in
      neurodegenerative diseases with special reference to their putative clinical
      relevance.

PMID- 22617145
TI  - Evaluation of the pathogenicity of GJB3 and GJB6 variants associated with
      nonsyndromic hearing loss.
AB  - A number of genes responsible for hearing loss are related to ion recycling and
      homeostasis in the inner ear. Connexins (Cx26 encoded by GJB2, Cx31 encoded by
      GJB3 and Cx30 encoded by GJB6) are core components of gap junctions in the inner
      ear. Gap junctions are intercellular communication channels and important factors
      that are associated with hearing loss. To date, a molecular genetics study of
      GJB3 and GJB6 as a causative gene for hearing loss has not been performed in
      Korea. This study was therefore performed to elucidate the genetic
      characteristics of Korean patients with nonsyndromic sensorineural hearing loss
      and to determine the pathological mechanism of hearing loss by analyzing the
      intercellular communication function of Cx30 and Cx31 variants. Sequencing
      analysis of the GJB3 and GJB6 genes in our population revealed a total of nine
      variants, including four novel variants in the two genes. Three of the novel
      variants (Cx31-p.V27M, Cx31-p.V43M and Cx-30-p.I248V) and two previously reported
      variants (Cx31-p.V84I and Cx30-p.A40V) were selected for functional studies using
      a pathogenicity prediction program and assessed for whether the mutations were
      located in a conserved region of the protein. The results of biochemical and
      ionic coupling tests showed that both the Cx31-p.V27M and Cx31-p.V84I variants
      did not function normally when each was expressed as a heterozygote with the wild
      type Cx31. This study demonstrated that two variants of Cx31 were pathogenic
      mutations with deleterious effect. This information will be valuable in
      understanding the pathogenic role of GJB3 and GJB6 mutations associated with
      hearing loss.

PMID- 22617146
TI  - Molecular basis of peroxisomal biogenesis disorders caused by defects in
      peroxisomal matrix protein import.
AB  - Peroxisomal biogenesis disorders (PBDs) represent a spectrum of autosomal
      recessive metabolic disorders that are collectively characterized by abnormal
      peroxisome assembly and impaired peroxisomal function. The importance of this
      ubiquitous organelle for human health is highlighted by the fact that PBDs are
      multisystemic disorders that often cause death in early infancy. Peroxisomes
      contribute to central metabolic pathways. Most enzymes in the peroxisomal matrix
      are linked to lipid metabolism and detoxification of reactive oxygen species.
      Proper assembly of peroxisomes and thus also import of their enzymes relies on
      specific peroxisomal biogenesis factors, so called peroxins with PEX being the
      gene acronym. To date, 13 PEX genes are known to cause PBDs when mutated. Studies
      of the cellular and molecular defects in cells derived from PBD patients have
      significantly contributed to the understanding of the functional role of the
      corresponding peroxins in peroxisome assembly. In this review, we discuss recent
      data derived from both human cell culture as well as model organisms like yeasts
      and present an overview on the molecular mechanism underlying peroxisomal
      biogenesis disorders with emphasis on disorders caused by defects in the
      peroxisomal matrix protein import machinery.

PMID- 22617147
TI  - The SENSE-Isomorphism Theoretical Image Voxel Estimation (SENSE-ITIVE) model for
      reconstruction and observing statistical properties of reconstruction operators.
AB  - The acquisition of sub-sampled data from an array of receiver coils has become a
      common means of reducing data acquisition time in MRI. Of the various techniques
      used in parallel MRI, SENSitivity Encoding (SENSE) is one of the most common,
      making use of a complex-valued weighted least squares estimation to unfold the
      aliased images. It was recently shown in Bruce et al. [Magn. Reson. Imag.
      29(2011):1267-1287] that when the SENSE model is represented in terms of a real
      valued isomorphism,it assumes a skew-symmetric covariance between receiver coils,
      as well as an identity covariance structure between voxels. In this manuscript,
      we show that not only is the skew-symmetric coil covariance unlike that of real
      data, but the estimated covariance structure between voxels over a time series of
      experimental data is not an identity matrix. As such, a new model, entitled SENSE
      ITIVE, is described with both revised coil and voxel covariance structures. Both
      the SENSE and SENSE-ITIVE models are represented in terms of real-valued
      isomorphisms, allowing for a statistical analysis of reconstructed voxel means,
      variances, and correlations resulting from the use of different coil and voxel
      covariance structures used in the reconstruction processes to be conducted. It is
      shown through both theoretical and experimental illustrations that the miss
      specification of the coil and voxel covariance structures in the SENSE model
      results in a lower standard deviation in each voxel of the reconstructed images,
      and thus an artificial increase in SNR, compared to the standard deviation and
      SNR of the SENSE-ITIVE model where both the coil and voxel covariances are
      appropriately accounted for. It is also shown that there are differences in the
      correlations induced by the reconstruction operations of both models, and
      consequently there are differences in the correlations estimated throughout the
      course of reconstructed time series. These differences in correlations could
      result in meaningful differences in interpretation of results.

PMID- 22617148
TI  - Comparison of dual-echo DSC-MRI- and DCE-MRI-derived contrast agent kinetic
      parameters.
AB  - The application of dynamic susceptibility contrast (DSC) MRI methods to assess
      brain tumors is often confounded by the extravasation of contrast agent (CA).
      Disruption of the blood-brain barrier allows CA to leak out of the vasculature
      leading to additional T(1), T(2) and T(2) relaxation effects in the extravascular
      space, thereby affecting the signal intensity time course in a complex manner.
      The goal of this study was to validate a dual-echo DSC-MRI approach that
      separates and quantifies the T(1) and T(2) contributions to the acquired signal
      and enables the estimation of the volume transfer constant, K(trans), and the
      volume fraction of the extravascular extracellular space, v(e). To test the
      validity of this approach, DSC-MRI- and dynamic contrast enhanced (DCE) MRI
      derived K(trans) and v(e) estimates were spatially compared in both 9L and C6 rat
      brain tumor models. A high degree of correlation (concordance correlation
      coefficients >0.83, Pearson's r>0.84) and agreement was found between the DSC-MRI
      and DCE-MRI-derived measurements. These results indicate that dual-echo DSC-MRI
      can be used to simultaneously extract reliable DCE-MRI kinetic parameters in
      brain tumors in addition to conventional blood volume and blood flow metrics.

PMID- 22617149
TI  - Novel methodology for 3D reconstruction of carotid arteries and plaque
      characterization based upon magnetic resonance imaging carotid angiography data.
AB  - In this study, we present a novel methodology that allows reliable segmentation
      of the magnetic resonance images (MRIs) for accurate fully automated three
      dimensional (3D) reconstruction of the carotid arteries and semiautomated
      characterization of plaque type. Our approach uses active contours to detect the
      luminal borders in the time-of-flight images and the outer vessel wall borders in
      the T(1)-weighted images. The methodology incorporates the connecting components
      theory for the automated identification of the bifurcation region and a knowledge
      based algorithm for the accurate characterization of the plaque components. The
      proposed segmentation method was validated in randomly selected MRI frames
      analyzed offline by two expert observers. The interobserver variability of the
      method for the lumen and outer vessel wall was -1.60%+/-6.70% and 0.56%+/-6.28%,
      respectively, while the Williams Index for all metrics was close to unity. The
      methodology implemented to identify the composition of the plaque was also
      validated in 591 images acquired from 24 patients. The obtained Cohen's k was
      0.68 (0.60-0.76) for lipid plaques, while the time needed to process an MRI
      sequence for 3D reconstruction was only 30 s. The obtained results indicate that
      the proposed methodology allows reliable and automated detection of the luminal
      and vessel wall borders and fast and accurate characterization of plaque type in
      carotid MRI sequences. These features render the currently presented methodology
      a useful tool in the clinical and research arena.

PMID- 22617151
TI  - Abi1, a critical molecule coordinating actin cytoskeleton reorganization with PI
      3 kinase and growth signaling.
AB  - Coordination of actin cytoskeletal reorganization with growth and proliferation
      signals is a key cellular process that is not fully understood. PI-3 kinase is
      one of the central nodes for distributing growth and proliferation signals
      downstream from growth factor receptors to the nucleus. Although PI-3 kinase
      function has been associated with actin cytoskeleton remodeling, satisfactory
      explanations of the mechanisms mediating this regulation have been elusive. Here
      we propose that interaction of the Abi1 protein with the p85 regulatory subunit
      of PI-3 kinase represents the link between growth receptor signaling and actin
      cytoskeleton remodeling. This function of Abi1, which involves WAVE complex, was
      initially observed in macropinocytosis, and may explain the coincident
      dysregulation of PI-3 kinase and actin cytoskeleton in cancer.

PMID- 22617150
TI  - Post-translational regulation of TGF-beta receptor and Smad signaling.
AB  - TGF-beta family signaling through Smads is conceptually a simple and linear
      signaling pathway, driven by sequential phosphorylation, with type II receptors
      activating type I receptors, which in turn activate R-Smads. Nevertheless, TGF
      beta family proteins induce highly complex programs of gene expression responses
      that are extensively regulated, and depend on the physiological context of the
      cells. Regulation of TGF-beta signaling occurs at multiple levels, including TGF
      beta activation, formation, activation and destruction of functional TGF-beta
      receptor complexes, activation and degradation of Smads, and formation of Smad
      transcription complexes at regulatory gene sequences that cooperate with a
      diverse set of DNA binding transcription factors and coregulators. Here we
      discuss recent insights into the roles of post-translational modifications and
      molecular interaction networks in the functions of receptors and Smads in TGF
      beta signal responses. These layers of regulation demonstrate how a simple
      signaling system can be coopted to exert exquisitely regulated, complex
      responses.

PMID- 22617152
TI  - High prevalence of occult hepatitis B virus infection in children born to HBsAg
      positive mothers despite prophylaxis with hepatitis B vaccination and HBIG.
AB  - BACKGROUND & AIMS: Occult hepatitis B virus (HBV) infection is a well-recognized
      clinical entity characterized by the detection of HBV DNA in serum and/or liver
      in the absence of detectable hepatitis B surface antigen (HBsAg). The frequency
      of the diagnosis depends on the relative sensitivity of both HBsAg and HBV DNA
      assays. We aimed at determining the prevalence of occult HBV infection in a high
      risk group of children who developed HBV infection despite immunoprophylaxis.
      METHODS: The sera of 75 children born to HBsAg-positive mothers previously
      immunized by HBIG and prophylaxic vaccine regimen were assayed for HBV DNA by
      real-time PCR. Subsequently, the samples were tested using a sensitive standard
      PCR, with an independent set of primers for all HBV genes, and analyzed by direct
      sequencing. RESULTS: HBV DNA was detected in 21/75 (28%) children, and ranged
      between 77 and 9240 copies/ml. All were positive for anti-HBs. Five (24%)
      children were found to be positive for anti-HBc, while anti-HBc-only positive
      individuals were not observed. Eight isolates (38%) did not carry any mutation.
      Thirteen infected children (62%) had at least one mutation in regions known to be
      involved in functional and/or immune epitope activity. Ten had G145R mutations.
      CONCLUSIONS: HBV occult infection seems to be relatively frequent in immunized
      children born to HBsAg-positive mothers. HBsAg negativity is not sufficient to
      completely exclude HBV DNA presence. These findings emphasize the importance of
      considering occult HBV infection in hypo-endemic areas.

PMID- 22617153
TI  - The Laennec staging system for histological sub-classification of cirrhosis is
      useful for stratification of prognosis in patients with liver cirrhosis.
AB  - BACKGROUNDS & AIMS: The clinical severity of cirrhosis varies widely. We
      investigated whether histological sub-classification of cirrhosis using the
      Laennec system can discriminate different outcomes among patients with cirrhosis.
      METHODS: One hundred and seventy-five patients with chronic liver disease who
      underwent liver biopsy and showed stage 3 or 4 fibrosis between January 2001 and
      December 2008 were prospectively enrolled. Cirrhosis was sub-classified into
      three groups (4A, 4B, and 4C) according to the Laennec system. The end point was
      liver-related event (LRE) occurrence, including decompensation, hepatocellular
      carcinoma, and liver-related death. RESULTS: The median age of the patients (110
      men, 65 women) was 55 years. Stages 3, 4A, 4B, and 4C were identified in 46
      (26.3%), 16 (9.1%), 82 (46.9%), and 31 (17.7%) patients, respectively. During the
      follow-up period, LREs occurred in 32 (18.3%) patients: 4 (8.7%) with stage 3, 2
      (12.5%) with stage 4A, 17 (20.7%) with stage 4B, and 9 (29.0%) with stage 4C. In
      a multivariate analysis, histological sub-classification of cirrhosis
      independently predicted LRE occurrence. While patients with stage 4A tended to be
      at higher risk of LRE occurrence than those with stage 3, patients with stages 4B
      and 4C had significantly higher risks of LRE occurrence, with hazard ratios of
      6.158 (p=0.016) and 8.945 (p=0.004), respectively. CONCLUSIONS: Histological sub
      classification of cirrhosis using the Laennec system can be used to assess the
      risk of LRE occurrence among patients with cirrhosis. Our study provides a solid
      basis for further studies of non-invasive methods for monitoring the risk of LRE
      occurrence and will help physicians to establish optimum treatment strategies.

PMID- 22617154
TI  - Role of Toll-like receptor 2 in the immune response against hepadnaviral
      infection.
AB  - BACKGROUND & AIMS: The Toll-like receptor 2 (TLR2) has recently been recognized
      to play an important role in the pathogenesis of chronic hepatitis B virus (HBV)
      infection. In the present study, we examined the role of TLR2 in hepadnaviral
      infection in hepatoma cell lines and the woodchuck model. METHODS: The expression
      of TLR2 and pro-inflammatory cytokines was quantified by real time RT-PCR. TLR2
      associated signaling pathways in hepatocytes were examined by Western blot. HBV
      replication and gene expression were assessed by Southern blot, Northern blot and
      specific ELISA, respectively. RESULTS: TLR2 ligands activated NF-kappaB,
      PI3K/Akt, and different arms of MAPK signaling pathways and induced the
      production of pro-inflammatory cytokines in hepatocytes. TLR2-mediated innate
      immune responses led to reduction of HBV/woodchuck hepatitis virus (WHV)
      replication and gene expression in HepG2.2.15 cells and primary woodchuck
      hepatocytes. Furthermore, the antiviral activity of TLR2 ligands was abolished by
      pretreatment with U0126 and rapamycin, inhibitors of the MAPK/ERK and PI3K/Akt
      pathways, respectively. In the woodchuck model, relatively low levels of TLR2
      expression were found in peripheral blood mononuclear cells (PBMCs) and in liver
      tissues from chronic WHV carriers. TLR2 expression in PBMCs was inversely
      correlated with WHV DNA titers in acute WHV infection and in entecavir-treated
      chronic WHV carriers. CONCLUSIONS: These data suggest that hepatocytes play an
      active role in TLR2-mediated antiviral responses during hepadnaviral infection.
      The mutual inhibition of HBV replication and TLR2 signaling represents an
      important aspect of HBV infection and should be considered in the new therapeutic
      concept against chronic HBV infection.

PMID- 22617155
TI  - Inactivation of Spry2 accelerates AKT-driven hepatocarcinogenesis via activation
      of MAPK and PKM2 pathways.
AB  - BACKGROUND & AIMS: Aberrant activation of the AKT oncogenic pathway and
      downregulation of the Sprouty 2 (Spry2) tumor suppressor gene are frequently
      observed molecular events in human hepatocarcinogenesis. The goal of the present
      study was to investigate the eventual biochemical and genetic crosstalk between
      activated AKT and inactivation of Spry2 during liver cancer development by using
      in vivo and in vitro approaches. METHODS: Activated AKT and/or Spry2Y55F, a
      dominant negative form of Spry2, were overexpressed in the mouse liver via
      hydrodynamic gene delivery. Histological and biochemical assays were applied to
      characterize the molecular features of AKT and AKT/Spry2Y55F liver tumors. The
      human HLE hepatocellular carcinoma (HCC) cell line, stably overexpressing AKT,
      was transfected with Spry2Y55F to study the molecular mechanisms underlying
      hepatocarcinogenesis driven by Spry2 loss. RESULTS: Spry2Y55F overexpression
      significantly accelerated AKT-induced hepatocarcinogenesis in the mouse.
      AKT/Spry2Y55F liver lesions had increased proliferation and glycolysis and
      decreased lipogenesis when compared with AKT corresponding lesions. At the
      molecular level, AKT/Spry2Y55F HCCs exhibited a significantly stronger induction
      of activated mitogen-activated protein kinase (MAPK) and pyruvate kinase M2
      (PKM2) pathways than in AKT corresponding lesions. This phenotype was reproduced
      in HLE cells overexpressing AKT following transfection with Spry2Y55F.
      Furthermore, we found that concomitant suppression of the MAPK cascade and PKM2
      strongly inhibited the growth induced by Spry2Y55F in AKT-overexpressing cells.
      CONCLUSIONS: Inactivation of Spry2 accelerates AKT-induced hepatocarcinogenesis
      via activation of MAPK and PKM2 pathways.

PMID- 22617156
TI  - Content of hypericins from plants and in vitro shoots of Hypericum undulatum
      Schousb. ex Willd.
AB  - This study reports the first quantification study of pseudohypericin (PsHyp) and
      hypericin (Hyp) in Hypericum undulatum Schousb. ex Willd in vitro cultures
      developed by a Portuguese company. Both compounds were quantified by high
      performance liquid chromatography and their levels were compared with those in
      commercial samples of Hypericum perforatum. PsHyp was found to be the major
      naphthodianthrone of H. undulatum, with an average ratio of 3.73:1 compared to
      Hyp. Significant statistical differences were found between the content of Hyp
      and PsHyp in H. undulatum regenerated shoots compared to in vivo samples. The
      mean concentration of total Hyps varied from 178.41 to 358.93 ug g(-1) dry
      extract in H. undulatum regenerated shoots, which is on average two to three
      times less than naphthodianthrone levels found in H. undulatum in vivo and H.
      perforatum commercial samples. However, none of the analysed samples presented
      the levels of Hyps required by the European and United States Pharmacopoeias.

PMID- 22617157
TI  - Interleukin-8 and its receptor CXCR2 in the tumour microenvironment promote colon
      cancer growth, progression and metastasis.
AB  - BACKGROUND: Colorectal cancer (CRC) is a leading cause of death in the United
      States. Increased level of interleukin-8 (IL-8) and CXCR2 on tumours and in the
      tumour microenvironment has been associated with CRC growth, progression and
      recurrence in patients. Here, we aimed to evaluate the effects of tissue
      microenvironment-encoded IL-8 and CXCR2 on colon cancer progression and
      metastasis. METHODS: A novel immunodeficient, skin-specific IL-8-expressing
      transgenic model was generated to evaluate colon cancer growth and metastasis.
      Syngeneic mouse colon cancer cells were grafted in CXCR2 knockout (KO) mice to
      study the contribution of CXCR2 in the microenvironment to cancer growth.
      RESULTS: Elevated levels of IL-8 in the serum and tumour microenvironment
      profoundly enhanced the growth of human and mouse colon cancer cells with
      increased peri-tumoural angiogenesis, and also promoted the extravasation of the
      cancer cells into the lung and liver. The tumour growth was inhibited in CXCR2 KO
      mice with significantly reduced tumour angiogenesis and increased tumour
      necrosis. CONCLUSION: Increased expression of IL-8 in the tumour microenvironment
      enhanced colon cancer growth and metastasis. Moreover, the absence of its
      receptor CXCR2 in the tumour microenvironment prevented colon cancer cell growth.
      Together, our study demonstrates the critical roles of the tumour
      microenvironment-encoded IL-8/CXCR2 in colon cancer pathogenesis, validating the
      pathway as an important therapeutic target.

PMID- 22617159
TI  - Computed tomography perfusion imaging denoising using gaussian process
      regression.
AB  - Brain perfusion weighted images acquired using dynamic contrast studies have an
      important clinical role in acute stroke diagnosis and treatment decisions.
      However, computed tomography (CT) images suffer from low contrast-to-noise ratios
      (CNR) as a consequence of the limitation of the exposure to radiation of the
      patient. As a consequence, the developments of methods for improving the CNR are
      valuable. The majority of existing approaches for denoising CT images are
      optimized for 3D (spatial) information, including spatial decimation (spatially
      weighted mean filters) and techniques based on wavelet and curvelet transforms.
      However, perfusion imaging data is 4D as it also contains temporal information.
      Our approach using gaussian process regression (GPR), which takes advantage of
      the temporal information, to reduce the noise level. Over the entire image, GPR
      gains a 99% CNR improvement over the raw images and also improves the quality of
      haemodynamic maps allowing a better identification of edges and detailed
      information. At the level of individual voxel, GPR provides a stable baseline,
      helps us to identify key parameters from tissue time-concentration curves and
      reduces the oscillations in the curve. GPR is superior to the comparable
      techniques used in this study.

PMID- 22617158
TI  - Inflammation marker and risk of pancreatic cancer: a nested case-control study
      within the EPIC cohort.
AB  - BACKGROUND: Established risk factors for pancreatic cancer include smoking, long
      standing diabetes, high body fatness, and chronic pancreatitis, all of which can
      be characterised by aspects of inflammatory processes. However, prospective
      studies investigating the relation between inflammatory markers and pancreatic
      cancer risk are scarce. METHODS: We conducted a nested case-control study within
      the European Prospective Investigation into Cancer and Nutrition, measuring
      prediagnostic blood levels of C-reactive protein (CRP), interleukin-6 (IL-6), and
      soluble receptors of tumour necrosis factor-alpha (sTNF-R1, R2) in 455 pancreatic
      cancer cases and 455 matched controls. Odds ratios (ORs) were estimated using
      conditional logistic regression models. RESULTS: None of the inflammatory markers
      were significantly associated with risk of pancreatic cancer overall, although a
      borderline significant association was observed for higher circulating sTNF-R2
      (crude OR=1.52 (95% confidence interval (CI) 0.97-2.39), highest vs lowest
      quartile). In women, however, higher sTNF-R1 levels were significantly associated
      with risk of pancreatic cancer (crude OR=1.97 (95% CI 1.02-3.79)). For sTNF-R2,
      risk associations seemed to be stronger for diabetic individuals and those with a
      higher BMI. CONCLUSION: Prospectively, CRP and IL-6 do not seem to have a role in
      our study with respect to risk of pancreatic cancer, whereas sTNF-R1 seemed to be
      a risk factor in women and sTNF-R2 might be a mediator in the risk relationship
      between overweight and diabetes with pancreatic cancer. Further large prospective
      studies are needed to clarify the role of proinflammatory proteins and cytokines
      in the pathogenesis of exocrine pancreatic cancer.

PMID- 22617160
TI  - Designing optimal universal pulses using second-order, large-scale, non-linear
      optimization.
AB  - Recently, RF pulse design using first-order and quasi-second-order pulses has
      been actively investigated. We present a full second-order design method capable
      of incorporating relaxation, inhomogeneity in B(0) and B(1). Our model is
      formulated as a generic optimization problem making it easy to incorporate
      diverse pulse sequence features. To tame the computational cost, we present a
      method of calculating second derivatives in at most a constant multiple of the
      first derivative calculation time, this is further accelerated by using symbolic
      solutions of the Bloch equations. We illustrate the relative merits and
      performance of quasi-Newton and full second-order optimization with a series of
      examples, showing that even a pulse already optimized using other methods can be
      visibly improved. To be useful in CPMG experiments, a universal refocusing pulse
      should be independent of the delay time and insensitive of the relaxation time
      and RF inhomogeneity. We design such a pulse and show that, using it, we can
      obtain reliable R(2) measurements for offsets within +/-gammaB(1). Finally, we
      compare our optimal refocusing pulse with other published refocusing pulses by
      doing CPMG experiments.

PMID- 22617161
TI  - Biochip data normalization using multifunctional probes.
AB  - Using a biochip with stable probe functionalization and a detection system
      capable of real time measurements, it is demonstrated that acquired probe-target
      interaction data are more reproducible in time--on a given probe spot using
      sequential target runs--than in space, using many probe spot replicates on the
      biochip in one single parallel target run. To increase the biochip data
      precision, a normalization method that quantifies and corrects the surface
      inhomogeneity without the use of complex data post-processing has been developed.
      This simple and effective method is based on adding a common reactive group to
      all probes and quantifying the biochip response to a calibration target, thus
      quantifying the spatial heterogeneity in the biosensor responsiveness. The
      usefulness of such methodology, which can be easily generalized, is demonstrated
      in the model case of DNA:DNA interactions, using a surface plasmon resonance
      imaging system as the dynamical reader. The biochips are based on streptavidin
      biochemically functionalized gold films onto which biotinylated ssDNA probe
      sequences, related to cystic fibrosis genotyping, are spotted. This normalization
      method provides high gain in data precision and allows, in this example,
      unambiguous genotyping of SNP, including discrimination of the heterozygote case
      from the two homozygote cases.

PMID- 22617162
TI  - The nature of nurture and the future of evodevo: toward a theory of developmental
      evolution.
AB  - This essay has three parts. First, I posit that much research in contemporary
      evodevo remains steeped in a traditional framework that views traits and trait
      differences as being caused by genes and genetic variation, and the environment
      as providing an external context in which development and evolution unfold.
      Second, I discuss three attributes of organismal development and evolution,
      broadly applicable to all organisms and traits that call into question the
      usefulness of gene- and genome-centric views of development and evolution. I then
      focus on the third and main aim of this essay and ask: what conceptual and
      empirical opportunities exist that would permit evodevo research to transcend the
      traditional boundaries inherited from its parent disciplines and to move toward
      the development of a more comprehensive and realistic theory of developmental
      evolution? Here, I focus on three conceptual frameworks, the theory of
      facilitated variation, the theory of evolution by genetic accommodation, and the
      theory of niche construction. I conclude that combined they provide a rich,
      interlocking framework within which to revise existing and develop novel
      empirical approaches toward a better understanding of the nature of developmental
      evolution. Examples of such approaches are highlighted, and the consequences of
      expanding existing frameworks are discussed.

PMID- 22617163
TI  - Exercise and social activity improve everyday function in long-term care
      residents.
AB  - OBJECTIVES: This study examined the effects of high-intensity resistance strength
      training and walking (E), individualized social activity (SA), and resistance
      training and walking combined with social activity (ESA) on everyday function in
      long-term care (LTC) residents and explored the relationship between change in
      everyday function and change in sleep. DESIGN: The study used data from The
      Effect of Activities and Exercise on Sleep, a randomized controlled trial.
      SETTING: Residential LTC facilities. PARTICIPANTS: A total of 119 participants
      who had measures of everyday function and sleep at baseline and postintervention.
      INTERVENTIONS: The E group exercised 5 days a week. The SA group was involved in
      social activities 5 days a week. The ESA group received both E and SA
      interventions. The usual care (UC) control group participated in usual
      activities. MEASUREMENTS: Everyday function was measured by the Nursing Home
      Physical Performance Test. Nighttime sleep was measured by attended
      polysomnography. RESULTS: The UC and SA groups showed a decline in everyday
      function, whereas the E and ESA groups showed improvement. There were
      statistically significant differences between the groups, with pairwise
      comparisons showing significant improvements in the ESA group over the SA group
      (95% confidence interval, -3.94 to -0.97) and the UC group (95% confidence
      interval, -3.69 to -0.64). No relationship was found between change in everyday
      function and change in sleep. CONCLUSION: Seven weeks of high-intensity
      resistance strength training and walking, combined with individualized social
      activities (ESA), improved everyday function among LTC residents, independent of
      change in sleep.

PMID- 22617164
TI  - A longitudinal study of poor sleep after inpatient post-acute rehabilitation: 
      the role of depression and pre-illness sleep quality.
AB  - OBJECTIVES: To explore the unique impact of poor sleep and symptoms of depression
      on sleep quality for up to 1 year after inpatient post-acute rehabilitation among
      older adults. DESIGN: Prospective longitudinal cohort study. SETTING: Two
      inpatient post-acute rehabilitation facilities. PARTICIPANTS: A total of 245
      individuals older than 65 years (mean age = 80 years, 38% women). INTERVENTIONS:
      None. MEASUREMENTS: Sleep quality was assessed with the Pittsburgh Sleep Quality
      Index (PSQI) during the post-acute care stay twice to evaluate pre-illness sleep
      quality and sleep quality during the post-acute care stay, and again at 3-, 6-, 9
      , and 12-month follow-up. Demographics, symptoms of depression, cognitive
      functioning, and comorbidities were also assessed. RESULTS: Across time points,
      sleep was significantly disturbed for many individuals. Nested regression models
      predicting PSQI total score at 3, 6, 9, and 12 months showed that variables
      entered in Block 1 (age, gender, cognitive functioning, and comorbidities) were
      significant predictors of poor sleep at 6-month follow-up but not at 3-, 9-, or
      12-month follow-up. Depression (Block 2) and pre-illness PSQI total score (Block
      3) were significant predictors of PSQI total score at all follow-up time points.
      PSQI total score during post-acute care (Block 4) explained a significant
      proportion of variance only at the 3-month follow-up. CONCLUSIONS: This study
      confirms that chronic poor sleep is common among older adults during post-acute
      rehabilitation and resolution of sleep disturbance after acute health events may
      be a lengthy process. Our findings expand understanding of the role of depressive
      symptoms and preexisting sleep complaints in predicting poor sleep over time
      among these vulnerable older adults.

PMID- 22617165
TI  - Formation of a centromere-specific chromatin structure.
AB  - The kinetochore is formed on centromeric DNA as a key interface with microtubules
      from the mitotic spindle to achieve accurate chromosome segregation during
      mitosis. However, in contrast to other regions of the chromosome, the position of
      the kinetochore is specified by sequence-independent epigenetic mechanisms. Most
      recent work on kinetochore specification has focused on the centromere-specific
      histone H3-variant CENP-A. Whereas CENP-A is an important epigenetic marker for
      the kinetochore specification, it is unclear how centromeric chromatin structure
      is organized. To understand centromeric chromatin structure, we focused on
      additional centromere proteins that have an intrinsic DNA binding activity and
      identified the DNA binding CENP-T-W-S-X complex. Tetramer formation of CENP-T-W-S
      X is essential for functional kinetochore assembly in vertebrate cells. Our
      structural and biochemical analysis reveals that the CENP-T-W-S-X complex is
      composed of four histone-fold domains with structural similarity to nucleosomes
      and displays DNA supercoiling activity. These results suggest that the CENP-T-W-S
      X complex forms a unique nucleosome-like structure at centromeric chromatin. In
      addition, CENP-S and CENP-X function at non-centromeric sites. The intriguing
      histone-like properties of these proteins suggest that they may form nucleosome
      like structures at various genome loci, extending the chromatin code beyond
      classical histone variants.

PMID- 22617166
TI  - Soft-robotic arm inspired by the octopus: II. From artificial requirements to
      innovative technological solutions.
AB  - Soft robotics is a current focus in robotics research because of the expected
      capability of soft robots to better interact with real-world environments. As a
      point of inspiration in the development of innovative technologies in soft
      robotics, octopuses are particularly interesting 'animal models'. Octopus arms
      have unique biomechanical capabilities that combine significant pliability with
      the ability to exert a great deal of force, because they lack rigid structures
      but can change and control their degree of stiffness. The octopus arm motor
      capability is a result of the peculiar arrangement of its muscles and the
      properties of its tissues. These special abilities have been investigated by the
      authors in a specific study dedicated to identifying the key principles
      underlying these biological functions and deriving engineering requirements for
      robotics solutions. This paper, which is the second in a two-part series,
      presents how the identified requirements can be used to create innovative
      technological solutions, such as soft materials, mechanisms and actuators.
      Experiments indicate the ability of these proposed solutions to ensure the same
      performance as in the biological model in terms of compliance, elongation and
      force. These results represent useful and relevant components of innovative soft
      robotic systems and suggest their potential use to create a new generation of
      highly dexterous, soft-bodied robots.

PMID- 22617167
TI  - Gut-derived lipopolysaccharide promotes T-cell-mediated hepatitis in mice through
      Toll-like receptor 4.
AB  - Robust clinical and epidemiologic data support the role of inflammation as a key
      player in hepatocellular carcinoma (HCC) development. Our previous data showed
      that gut-derived lipopolysaccharide (LPS) promote HCC development by activating
      Toll-like receptor 4 (TLR4) expressed on myeloid-derived cells. However, the
      effects of gut-derived LPS on other types of liver injury models are yet to be
      studied. The purpose of this study was to determine the importance of gut-derived
      LPS and TLR4 signaling in a T-cell-mediated hepatitis-Con A-induced hepatitis
      model, which mimic the viral hepatitis. Reduction of endotoxin using antibiotics
      regimen or genetic ablation of TLR4 in mice significantly alleviate Con A-induced
      liver injury by inhibiting the infiltration of T lymphocytes into the liver and
      the activation of CD4(+) T lymphocytes as well as the production of T helper 1
      cytokines; in contrast, exogenous LPS can promote Con A-induced hepatitis and
      CD4(+) T cells activation in vivo and in vitro. Reconstitution of TLR4-expressing
      myeloid cells in TLR4-deficient mice restored Con A-induced liver injury and
      inflammation, indicating the major cell target of LPS. In addition, TLR4 may
      positively regulate the target hepatocellular apoptosis via the perforin/granzyme
      B pathway. These data suggest that gut-derived LPS and TLR4 play important
      positive roles in Con A-induced hepatitis and modulation of the gut microbiotia
      may represent a new avenue for therapeutic intervention to treat acute hepatitis
      induced by hepatitis virus infection, thus to prevent hepatocellular carcinoma.

PMID- 22617168
TI  - Key principles and clinical applications of "next-generation" DNA sequencing.
AB  - Demand for fast, inexpensive, and accurate DNA sequencing data has led to the
      birth and dominance of a new generation of sequencing technologies. So-called
      "next-generation" sequencing technologies enable rapid generation of data by
      sequencing massive amounts of DNA in parallel using diverse methodologies which
      overcome the limitations of Sanger sequencing methods used to sequence the first
      human genome. Despite opening new frontiers of genomics research, the fundamental
      shift away from the Sanger sequencing that next-generation technologies has
      created has also left many unaware of the capabilities and applications of these
      new technologies, especially those in the clinical realm. Moreover, the brisk
      evolution of sequencing technologies has flooded the market with commercially
      available sequencing platforms, whose unique chemistries and diverse applications
      stand as another obstacle restricting the potential of next-generation
      sequencing. This review serves to provide a primer on next-generation sequencing
      technologies for clinical researchers and physician scientists. We provide an
      overview of the capabilities and clinical applications of DNA sequencing
      technologies to raise awareness among researchers about the power of these novel
      genomic tools. In addition, we discuss that key sequencing principles provide a
      comparison between existing and near-term technologies and outline key advantages
      and disadvantages between different sequencing platforms to help researchers
      choose an appropriate platform for their research interests.

PMID- 22617169
TI  - Residents living in residential care facilities: United States, 2010.
AB  - In 2010, residential care residents were mostly female, non-Hispanic white, and
      aged 85 and over, and had a median length of stay of about 22 months. For about
      20% of residents-or 137,700 persons-Medicaid paid for at least some long-term
      care services provided by the RCF. This estimate is similar to that found in a
      recent study (3). Almost 40% of all residential care residents received
      assistance with three or more ADL limitations, and over 40% had Alzheimer's
      disease or other dementias. These findings suggest a vulnerable population with a
      high burden of functional and cognitive impairment. Residential care is an
      important component of the U.S. long-term care system. This report presents
      national estimates of people living in RCFs, using data from the first-ever
      national probability sample survey of RCFs with four or more beds. This brief
      profile of residential care residents may provide useful information to
      policymakers, providers, and consumer advocates as they plan for the future long
      term care needs of older as well as younger adults. In addition, these findings
      serve as baseline national estimates as researchers continue to track the growth
      of and changes in the residential care industry.

PMID- 22617170
TI  - The actual management of tumor and vertebral compression fractures.
AB  - Tumor related fractures of the spine frequently dictate surgical management. The
      most critical factors influencing the need and type of surgery are degree of
      epidural cord compression, radiosensitivity of the tumor, presence of spinal
      instability and patient medical status/ estimated survivorship. There is a wide
      spectrum of therapeutic options: major en bloc resections in primary or
      oligometastatic disease; decompression and fusion in non-radiosensitive tumors
      with cord compression followed by adjuvant radiation therapy (RT); kyphoplasty/
      vertebroplasty for stable compression fractures or minimally invasive corpectomy
      for more unstable fractures and RT- only for radiosensitive tumors not causing
      overt instability. Radiation therapy has always been essential component of the
      treatment algorithm although it has been displaced from principal treatment
      modality in the last 2 decades. However, the advent of more targeted and
      efficient forms of RT (radiosurgery) may be a new treatment paradigm for more
      radioresistant tumors and may obviate the need for major operations.

PMID- 22617171
TI  - Bone grafting and substitutes in spine surgery.
AB  - The increase of spinal procedures over the last decades has made the long-term
      problems, such as pseudarthrosis, apparent. This demands optimized strategies,
      techniques and technologies. Modern fixation systems have been developed as an
      adjunct to spinal fusion, and several generations of different synthetic cages
      have proved to be reasonable alternatives to autologous bone or allografts. The
      development of recombinant bone morphogenetic proteins (BMPs) is of promise,
      because of their great osteoinductive capabilities. While spine surgeons are
      familiar with autologous and synthetic grafts as well as allografts, these
      comparably new evolving growth-factor-based technologies are of high interest.
      This was a selective literature review. Alternatives to autologous grafts include
      allograft bone, synthetic cages and growth-factor based bone substitutes, BMPs
      being the most-studied among them. Autologous iliac crest alone provides all of
      the required capabilities of an ideal bone graft, i.e. osteoconduction,
      osteoinduction, osteogenesis, but each of the alternatives can produce excellent
      results in a number of indications. If combined, these alternatives can
      cumulatively provide all required graft capabilities. Nevertheless, all of the
      available grafts have specific characteristics and can feature certain
      complications. Alternatives to autologous grafts circumvent donor-site morbidity
      and are available in a larger amount than autologous bone for extensive surgery.
      New technologies offer excellent possibilities of new bone formation, but there
      are also severe risks and high costs to be considered. The indication for bone
      grafting must be clearly defined, the graft selection should be individually
      adapted, and the risks, efforts and costs of the selected fusion procedure should
      be carefully considered.

PMID- 22617172
TI  - Minimal access to the posterolateral lumbar spine.
AB  - The purported advantages of minimally invasive spine surgery over open
      microsurgical alternatives for lumbar decompression and fusion are attractive to
      patients, surgeons, and hospital administrators. Shorter hospital length of stay,
      less blood loss, shorter operating times, decreased use of postoperative narcotic
      analgesics, and a more rapid return to work have all been touted as advantages.
      In this review, we describe step-by-step techniques for minimal access
      posterolateral lumbar decompression and fusion. Key learning tasks for the
      introduction of each technique into practice are highlighted. The current quality
      of evidence for each approach is also critically evaluated.

PMID- 22617173
TI  - Use of percutaneous kyphoplasty and vertebroplasty in spinal surgery.
AB  - The use of percutaneous vertebroplasty (PVP) was first described in 1987;
      however, since its conception its use has broadened. PVP involves the
      transpedicular injection of polymethylmethacrylate (PMMA) into the vertebral body
      for treatment of osteoporotic compression fractures. This paper reviews the
      history of PVP and percutaneous kyphoplasty (PKP), the epidemiology of
      osteoporotic fractures, key articles regarding its usage, and novel areas of
      application.

PMID- 22617174
TI  - Spinal emergencies.
AB  - True spinal emergencies are rare and represent a potential loss of function if
      not treated properly. This review describes the most frequently encountered
      spinal emergencies. Early diagnosis is the key to preventing significant
      morbidity in the form of permanent disability. The recognition of red flags,
      followed by a thorough neurologic exam and appropriate imaging, should prompt a
      thorough examination with a heightened sense of urgency regarding the workup for
      serious forms of pathology. Spinal emergencies threaten loss of function if not
      treated properly. Providers must be aware of the presenting symptoms and be able
      to accurately interpret imaging results in order to promptly diagnose and treat
      these conditions.

PMID- 22617175
TI  - Early predictive factors on mortality in head injured patients: a retrospective
      analysis of 112 traumatic brain injured patients.
AB  - AIM: Early hyperglycemia is a feature of traumatic brain injured (TBI) patients.
      The aim of our study was to analyze the impact of early hyperglycemia on in-ICU
      mortality in isolated TBI and its correlations with other factors responsible for
      secondary injury. METHODS: We studied admission values (AV) and worse values in
      the first 48 hours (WV 48 h) of 112 ICU TBI patients (mortality 29.6%) of blood
      glucose (BG), base excess (BE), mean arterial pressure (MAP), PaO2/FiO2 ratio and
      serum hemoglobin (Hb). Predictive strength as the area under the receiver
      operating curves (AUROC) and correlation between all variables were calculated.
      RESULTS: Data are expressed as median, 1st-3rd quartile. Both BG AV (147.5, 126
      182 mg/dL; AUROC 0.716, P=0.0002) and WV 48 h (156.5, 132-192 mg/dL; AUROC 0.721,
      P=0.0001) are predictive of mortality. AV and WV 48 h are respectively: PaO2/FiO2
      (366.8, 237.2-477.6 vs. 320, 214.4-426; P=0.05), MAP (90, 80-100.5 vs. 75, 66-83
      mmHg; P<0.0001) and Hb (11.4, 9.7-13.1 vs. 10.6, 9-12.2 g/dL; P<0.02). BG AV and
      WV 48 h correlates with: age (r=0.419, P<0.0001 and r=0.489, P<0.0001), PaO2/FiO2
      AV (r -0.223, P<0.03 and r -0.236, P<0.02), PaO2/FiO2 WV 48 h (r -0.215, P<0.03
      and r -0.279, P<0.005) and MAP WV 48 h (r -0.216, P<0.03 and r -0.261, P<0.007).
      CONCLUSION: Early hyperglycemia is a major predictor of mortality and correlates
      with other factors responsible for secondary injury. Early hyperglycemia seems to
      be a marker of inflammatory reaction responsible for early cardiovascular and
      respiratory impairment.

PMID- 22617176
TI  - Predictive value of inferior fronto-occipital fasciculus (IFO) DTI-fiber tracking
      for determining the extent of resection for surgery of frontal and temporal
      gliomas preoperatively.
AB  - AIM: This work reports the analysis of the relationship between inferior fronto
      occipital fasciculus (IFO), neoplastic lesions and surgical resection, in
      patients operated for gliomas located in the frontal, temporal and insular lobes
      of the dominant hemisphere. Aim of the study is evaluating the predictive value
      of inferior fronto-occipital fasciculus DTI-fiber tracking (FT) for determining
      the extent of resection preoperatively. METHODS: We selected 38 cases affected by
      lesions located in the frontal, temporal and insular lobes of the dominant
      hemisphere, which were related to the trajectory of the IFO. For each patient
      preoperative and postoperative MR images and DTI-FT were loaded into the
      neuronavigation system and merged; volumetric scan analysis was used for
      establishing tumor location and topography, as well as the volume of the lesion
      and of the residual tumor. All preoperative fiber tracking datasets were
      evaluated and the position of the tract (IFO) compared to the tumor was recorded.
      Postoperative MR scans were then compared with DTI-FT, in order to evaluate the
      correspondence between the resection boundaries and the trajectory of the fiber
      tract. RESULTS: Amongst the cases in which the IFO was inside the lesion, we
      found only incomplete resections (5 subtotal and 6 partial resections), while
      considering the cases in which the IFO was located outside the tumor, it was
      possible to perform a relevant (total/subtotal) resection in 18 of them (78%).
      CONCLUSION: FT of the inferior frontal-occipital fasciculus predicts the
      possibility and the extent of the resection for a frontal, temporal and/or
      insular lesion of the dominant hemisphere.

PMID- 22617177
TI  - Non-infected carotid artery pseudoaneurysm 29 years after endarterectomy,
      endovascular management with covered stent.
AB  - Pseudoaneurysm formation is a rare complication following carotid endarterectomy
      (CEA). Arterial pseudoaneurysms lack all three layers of the arterial wall that
      include the intima, media and adventitia. Pseudoaneurysms are most commonly seen
      after injuries to the artery in the form of blunt trauma and puncture, and are
      less common after surgeries such as carotid endarterectomy. These lesions present
      most frequently as enlarging, pulsatile, expandable masses associated with
      swelling and pain. Management of this complication is challenging. Traditionally,
      open surgical repair has been the preferred treatment. Recently, endovascular
      techniques using stent graft implantation alone or combined graft and coil
      embolization have offered a less invasive approach for the management of this
      lesion. Pseudoaneurysm development has been described within hours to several
      years after initial arterial injury, normally presenting within 5 years. To our
      knowledge, this is the first case report of pseudoaneurysm formation in a patient
      presenting 29 years after a carotid endarterectomy; during that time the patient
      remained completely asymptomatic until 2 months prior to his admission. The
      patient is an 84-year-old male with a history of stroke which prompted a left
      carotid endarterectomy in 1981. Twenty-nine years post procedure it was noted
      that the patient had a lump that was progressively enlarging on the left side of
      his neck, zone 1. It was pulsatile on examination. MRI/A imaging suggested a left
      carotid bulb aneurysm. The consulting vascular surgeon felt the patient would not
      be a good surgical candidate and so stenting was considered. Carotid and cerebral
      angiogram demonstrated a large 6 cm left carotid pseudoaneurysm off the carotid
      bulb. The diagnostic procedure was followed by a successful placement of an 8 x
      10 cm Viabahn covered stent from the left common carotid artery to the left
      internal carotid artery. Following the procedure, the carotid artery was patent
      and there was minimal to no further residual filling of the pseudoaneurysm.
      Poststenting, the patient remained at his neurological baseline. This case
      demonstrates that pseudoaneurysm formation can occur as a long term complication
      after carotid endarterectomy. It may present as a rapidly expandable, pulsatile,
      vascular lesion in the absence of clinical and sub-clinical infection. Placement
      of an endovascular stent graft may be a safe and effective option for treatment
      of infected and non-infected carotid pseudoaneurysm.

PMID- 22617178
TI  - Surgical treatment for combined hemifacial spasm and atypical trigeminal
      neuralgia caused by a tortuous basilar artery. Case report and review of the
      literature.
AB  - Simultaneous hemifacial spasm (HFS) and trigeminal neuralgia caused by cranial
      nerve (CN) compression from a tortuous basilar artery (BA) is very rare. We
      report a case of a 66-year-old man who presented with both HFS and "atypical"
      trigeminal neuralgia. The patient had a tortuous BA compressing both CN V and
      VII. The patient underwent microvascular decompression after failing conservative
      medical management. To the best of our knowledge this is the first reported case
      of both HFS and "atypical" trigeminal neuralgia that were both successfully
      treated by surgical intervention. We report the management of this rare
      combination and review the literature.

PMID- 22617179
TI  - Difficult airway in a patient with periodontoid synovial pannus due to psoriatic
      arthritis.

PMID- 22617180
TI  - Simultaneous occurrence of a glioblastoma multiforme juxtaposed to a meningioma.

PMID- 22617181
TI  - Combined supra/infratentorial approach to meningiomas of the transverse sinus.

PMID- 22617182
TI  - Deconvolution of vibroacoustic images using a simulation model based on a three
      dimensional point spread function.
AB  - Vibro-acoustography (VA) is a medical imaging method based on the difference
      frequency generation produced by the mixture of two focused ultrasound beams. VA
      has been applied to different problems in medical imaging such as imaging bones,
      microcalcifications in the breast, mass lesions, and calcified arteries. The
      obtained images may have a resolution of 0.7-0.8mm. Current VA systems based on
      confocal or linear array transducers generate C-scan images at the beam focal
      plane. Images on the axial plane are also possible, however the system resolution
      along depth worsens when compared to the lateral one. Typical axial resolution is
      about 1.0cm. Furthermore, the elevation resolution of linear array systems is
      larger than that in lateral direction. This asymmetry degrades C-scan images
      obtained using linear arrays. The purpose of this article is to study VA image
      restoration based on a 3D point spread function (PSF) using classical
      deconvolution algorithms: Wiener, constrained least-squares (CLSs), and geometric
      mean filters. To assess the filters' performance on the restored images, we use
      an image quality index that accounts for correlation loss, luminance and contrast
      distortion. Results for simulated VA images show that the quality index achieved
      with the Wiener filter is 0.9 (when the index is 1.0 this indicates perfect
      restoration). This filter yielded the best result in comparison with the other
      ones. Moreover, the deconvolution algorithms were applied to an experimental VA
      image of a phantom composed of three stretched 0.5mm wires. Experiments were
      performed using transducer driven at two frequencies, 3075kHz and 3125kHz, which
      resulted in the difference-frequency of 50kHz. Restorations with the theoretical
      line spread function (LSF) did not recover sufficient information to identify the
      wires in the images. However, using an estimated LSF the obtained results
      displayed enough information to spot the wires in the images. It is demonstrated
      that the phase of the theoretical and the experimental PSFs are dissimilar. This
      fact prevents VA image restoration with the current theoretical PSF. This study
      is a preliminary step towards understanding the restoration of VA images through
      the application of deconvolution filters.

PMID- 22617183
TI  - Antidepressant use in persons aged 12 and over: United States, 2005-2008.
AB  - In 2005-2008, 11% of Americans aged 12 and over took antidepressant medication.
      There were significant differences in antidepressant medication usage rates
      between groups. Females were 21/2 times as likely as males to take
      antidepressants. Antidepressant use was higher in persons aged 40 and over than
      in those aged 12-39. Non-Hispanic white persons were more likely to take
      antidepressants than other race and ethnicity groups. Other studies have shown
      similar age, gender, and race and ethnicity patterns (2,3). There was no
      variation in antidepressant use by income group. Among persons taking
      antidepressants overall, there was no significant difference in length of use
      between males and females. Among persons taking antidepressants, males were more
      likely than females to have seen a mental health professional in the past year.
      About 8% of persons aged 12 and over with no current depressive symptoms took
      antidepressant medication. This group may include persons taking antidepressants
      for reasons other than depression and persons taking antidepressants for
      depression who are being treated successfully and do not currently have
      depressive symptoms.Slightly over one-third of persons aged 12 and over with
      current severe depressive symptoms were taking antidepressants. According to
      American Psychiatric Association guidelines, medications are the preferred
      treatment for moderate to severe depressive symptomatology (4). The public health
      importance of increasing treatment rates for depression is reflected in Healthy
      People 2020, which includes national objectives to increase treatment for
      depression in adults and treatment for mental health problems in children (5).

PMID- 22617184
TI  - Cannot cannulate:  bonulate!

PMID- 22617185
TI  - Oral carbohydrate treatment before surgery.

PMID- 22617186
TI  - Reduction of biting and chewing of horses using differential reinforcement of
      other behavior.
AB  - Biting and chewing by horses on crossties can result in injury to the handler and
      damage to equipment. Operant-conditioning techniques have been used to train
      horses and could be used to reduce or eliminate undesirable biting and chewing.
      Presently, a differential-reinforcement-of-other-behavior (DRO) schedule, in the
      context of a reversal design, was effective in reducing biting and chewing in two
      horses. In DRO schedules, a reinforcer is delivered contingent on the absence of
      a target behavior for a specified interval. Positive-reinforcement procedures
      offer an alternative to aversive-control techniques typically used in equine
      training and may provide for better equine welfare and horse-human interaction.

PMID- 22617187
TI  - Evaluation of food and nutrient intake assessment using concentration biomarkers
      in European adolescents from the Healthy Lifestyle in Europe by Nutrition in
      Adolescence study.
AB  - Accurate food and nutrient intake assessment is essential for investigating diet
      disease relationships. In the present study, food and nutrient intake assessment
      among European adolescents using 24 h recalls (mean of two recalls) and a FFQ
      (separately and the combination of both) were evaluated using concentration
      biomarkers. Biomarkers included were vitamin C, beta-carotene, DHA+EPA, vitamin
      B12 (cobalamin and holo-transcobalamin) and folate (erythrocyte folate and plasma
      folate). For the evaluation of the food intake assessment 390 adolescents were
      included, while 697 were included for the nutrient intake assessment evaluation.
      Spearman rank and Pearson correlations, and validity coefficients, which are
      correlations between intake estimated and habitual true intake, were calculated.
      Correlations were higher between frequency of food consumption (from the FFQ) and
      concentration biomarkers than between mean food intake (from the recalls) and
      concentration biomarkers, especially for DHA+EPA (r 0.35 v. r 0.27). Most
      correlations were higher among girls than boys. For boys, the highest validity
      coefficients were found for frequency of fruit consumption (0.88) and for DHA+EPA
      biomarker (0.71). In girls, the highest validity coefficients were found for
      fruit consumption frequency (0.76), vegetable consumption frequency (0.74), mean
      fruit intake (0.90) and DHA+EPA biomarker (0.69). After exclusion of
      underreporters, correlations slightly improved. Correlations between usual food
      intakes, adjusted for food consumption frequency, and concentration biomarkers
      were higher than correlations between mean food intakes and concentration
      biomarkers. In conclusion, two non-consecutive 24 h recalls in combination with a
      FFQ seem to be appropriate to rank subjects according to their usual food intake.

PMID- 22617189
TI  - It is all about heart rate. Or is it?

PMID- 22617188
TI  - Effects on outcomes of heart rate reduction by ivabradine in patients with
      congestive heart failure: is there an influence of beta-blocker dose?: findings
      from the SHIFT (Systolic Heart failure treatment with the I(f) inhibitor
      ivabradine Trial) study.
AB  - OBJECTIVES: This study used the SHIFT (Systolic Heart failure treatment with the
      I(f) inhibitor ivabradine Trial) database to assess the impact of background beta
      blocker dose on response to ivabradine. BACKGROUND: In systolic heart failure,
      reduction in relatively high heart rates improves clinical outcomes when achieved
      with beta-blockers and even more so when the sinus node inhibitor ivabradine also
      is added. METHODS: Among patients with systolic heart failure, sinus rhythm, and
      heart rate >=70 beats/min on recommended background therapy, maximally tolerated
      beta-blocker doses were subgrouped as no beta-blocker, <25%, 25% to <50%, 50% to
      <100%, and 100% of European Society of Cardiology-suggested target doses. The
      impact of ivabradine on cardiovascular death or heart failure hospitalization
      (primary endpoint) was analyzed in each subgroup as time-to-first event using Cox
      models adjusted for heart rate. The statistical models assessed heterogeneity and
      trend of the treatment effect across subgroups, and an additional analysis was
      made adjusting for the interaction of randomized treatment with baseline heart
      rate. RESULTS: The primary endpoint and heart failure hospitalizations were
      significantly reduced by ivabradine in all subgroups with <50% of target beta
      blocker dose, including no beta-blocker (p = 0.012). Despite an apparent trend to
      reduction in treatment-effect magnitude with increasing beta-blocker dose, no
      variation in treatment effect was seen in general heterogeneity interaction tests
      (p = 0.35). Across beta-blocker subgroups, treatment effect was borderline
      nonsignificant only for the primary endpoint (p = 0.056), and significance was
      further lost after adjusting for interaction between baseline heart rate and
      ivabradine effect (p = 0.14). CONCLUSIONS: The magnitude of heart rate reduction
      by beta-blocker plus ivabradine, rather than background beta-blocker dose,
      primarily determines subsequent effect on outcomes. (Effects of ivabradine on
      cardiovascular events in patients with moderate to severe chronic heart failure
      and left ventricular systolic dysfunction. A three-year randomised double-blind
      placebo-controlled international multicentre study; ISRCTN70429960)

PMID- 22617190
TI  - A novel exo-cellulase from white spotted longhorn beetle (Anoplophora malasiaca).
AB  - Wood feeding insects depends heavily on the secretion of a combination of
      cellulases, mainly endoglucanases and other glucanases such as exoglucanases and
      xylanases, for efficient digestion of the cellulosic materials. To date, although
      a high number of endoglucanases have been found in xytophagous insects, little is
      known about exoglucanases encoded in the genome of these insects. Here we report
      the identification and isolation of an exoglucanase, designated as AmCel-5B, from
      the white spotted longhorn beetle, Anoplophora malasiaca. The optimal condition
      of enzymatic activity was found to be 50  degrees C and pH 4.0. Interestingly,
      this enzyme is not only exhibited exo-beta-glucanase activity, but also with
      obvious endo-beta-glucanase activity. Furthermore, this enzyme is unique in that,
      although it recognizes Avicel, evidenced as an exo-beta-glucanase, it cannot
      recognize oligosaccharides smaller than cellohexaose. This may explain why
      longhorn beetle can well digest hard "living" wood, which contains primarily
      rigid long fibers. Although it is known that metal ions can enhance the activity
      of some cellulases, we further demonstrated that reducing agent could work
      synergistically with metal ions for significant activity enhancement of AmCel-5B.
      The discovery and investigation of an insect exoglucanase should lead to a
      greater understanding of the mechanism for efficient digestion of cellulosic
      materials by wood feeding insects, as well as facilitate their potential
      applications in the production of bioenergy and biomaterials from lignocellulosic
      biomass in the future.

PMID- 22617191
TI  - Molecular and biochemical characterization of the major royal jelly protein in
      bumblebees suggest a non-nutritive function.
AB  - Honeybee queens are generated on purpose by extensive feeding with a glandular
      secretion termed royal jelly. Major royal jelly proteins (MRJPs) are the dominant
      proteinaceous component of royal jelly. One of them, MRJP1, was found to play a
      central role in honeybee queen development. Genes encoding MRJPs were reported to
      originate from a single originator, and several of them have evolved nutritive
      function. Phylogenetic analysis provides evidence that the same originator has
      multiplied independently in Nasonia and ant lineages. Here we show that
      bumblebees represent a transition species preserving a single-copy pre
      multiplication stage of MRJP evolution. By exploring the single-copy BtRJPL gene,
      we found striking similarities with MRJPs of the honeybee such as gene structure
      and expression regulation. At the same time it turned out that BtRJPL does not
      fulfill criteria for functioning as a nutritive protein. Instead we found
      evidence that BtRJPL is involved in food digestion or modification, which appears
      to be the original MRJP function, at least in this lineage. Thus, the
      evolutionary pattern of MRJPs in hymenopterans constitutes an excellent example
      of a functional diversification combined with the origin of new properties
      followed by intensive gene duplication events.

PMID- 22617192
TI  - Transmission Raman spectroscopy for quality control in model cocrystal tablets.
AB  - Transmission Raman spectroscopy is employed for the first time to analyse model
      formulations comprising tabletted cocrystals. The ability of transmission Raman
      to differentiate between formulations on the basis of both drug loading and drug
      chemistry (cocrystal versus separate components) is investigated.

PMID- 22617193
TI  - Molecular characterization of prostaglandin F receptor (FP) and E receptor
      subtype 1 (EP1) in zebrafish.
AB  - Prostaglandins E (PGE) and F (PGF) mediate diverse physiological functions via
      their cell surface receptors - prostaglandin E receptor (EP) subtypes 1, 2, 3 and
      4 (EP(1); EP(2); EP(3); EP(4)) and F receptor (FP). In teleost fishes, PGE was
      implicated in gill epithelium ion transport, while both PGE and PGF were involved
      in oocyte maturation, follicular rupture and coordination of reproductive
      behaviors. However, little is known about the mechanisms behind their actions. In
      present study, we first identified the full-length ORF cDNA clones of three
      zebrafish prostaglandin E receptor subtype 1 (zEP(1)) isoforms - zEP(1a), zEP(1b)
      and zEP(1c) - and FP (zFP) from adult ovary. RT-PCR showed that zEP(1a), zEP(1b)
      and zFP are widely expressed in adult tissues, while zEP(1c) mRNA expression is
      mainly confined in brain and kidney. Using a pGL3-NFAT-RE luciferase reporter
      system, both zEP(1a) and zEP(1b) expressed in DF-1 cells were shown to be
      activated by PGE(2) potently while zEP(1c) and zFP were activated by PGF(2a)
      effectively, suggesting that the four receptors are functionally coupled to
      intracellular Ca(2+)-signaling pathway. Furthermore, EP1a and EP1b, but not EP1c
      were suggested to couple to cAMP-PKA signaling pathway using a pGL3-CRE
      luciferase reporter assay. Although zEP(1c) might originate as a paralog to
      zEP(1a) and zEP(1b), its functional coupling to PGF(2alpha) instead of PGE(2)
      suggested that zEP(1) isoforms might have sub-functionalized in their ligand
      binding and G protein coupling specificity, in addition to differential tissue
      distribution. Characterization of these receptors undoubtedly furthered our
      understanding on the diverse yet highly target-specific responses of
      prostaglandins in teleosts.

PMID- 22617194
TI  - Quivers of curare-tipped blow gun darts.

PMID- 22617195
TI  - Codrenin.

PMID- 22617196
TI  - The Souchon anesthetizer.

PMID- 22617197
TI  - Casing Cunningham's apparatus.

PMID- 22617198
TI  - Neonatal craniosynostosis:  considerations.

PMID- 22617199
TI  - Intraoperative blood pressure measurement modalities are separate and not equal.

PMID- 22617201
TI  - A train-of-four count should be a train-of-four count, independently of the
      method it was determined with.

PMID- 22617203
TI  - Neurophysiologic monitoring during thoracoabdominal aortic aneurysm surgery.

PMID- 22617205
TI  - Confirmation of nonanesthetic-induced malignant hyperthermia.

PMID- 22617207
TI  - Perioperative role of methadone in adolescent patients.

PMID- 22617214
TI  - A method for small-animal PET/CT alignment calibration.
AB  - Small-animal positron-emission tomography/computed tomography (PET/CT) scanners
      provide anatomical and molecular imaging, which enables the joint visualization
      and analysis of both types of data. A proper alignment calibration procedure is
      essential for small-animal imaging since resolution is much higher than that in
      human devices. This work presents an alignment phantom and two different
      calibration methods that provide a reliable and repeatable measurement of the
      spatial geometrical alignment between the PET and the CT subsystems of a hybrid
      scanner. The phantom can be built using laboratory materials, and it is meant to
      estimate the rigid spatial transformation that aligns both modalities. It
      consists of three glass capillaries filled with a positron-emitter solution and
      positioned in a non-coplanar triangular geometry inside the system field of view.
      The calibration methods proposed are both based on automatic line detection, but
      with different approaches to calculate the transformation of the lines between
      both modalities. Our results show an average accuracy of the alignment estimation
      of 0.39 mm over the whole field of view.

PMID- 22617213
TI  - Contribution of NK cells to the innate phase of host protection against an
      intracellular bacterium targeting systemic endothelium.
AB  - We investigated the mechanisms by which natural killer (NK) cells mediate innate
      host defense against infection with an endothelium-targeting intracellular
      bacterium, Rickettsia. We found that a robust Rickettsia-induced innate response
      in resistant mice cleared the bacteria early in the infection and was associated
      with significantly higher frequencies of splenic interferon (IFN)-gamma (+)
      CD8(+) T cells and cytotoxic NK cells compared with susceptible mice. More
      importantly, NK cell-deficient Rag(-/-)gammac(-/-) animals displayed
      significantly increased susceptibility to Rickettsia infection compared with NK
      cell-sufficient Rag(-/-) mice, as evidenced by impaired bacterial clearance,
      early development of severe thrombosis in the liver, and a decreased serum level
      of IFN-gamma. Furthermore, the lack of NK cells also impaired host resistance of
      CB-17 scid mice to Rickettsia, similar to what was observed in Rag(-/-)gammac(-/
      ) mice. Interestingly, perforin deficiency in Rag(-/-)Prf1(-/-) mice resulted in
      greater thrombosis and insignificantly different systemic levels of IFN-gamma
      compared with Rag(-/-) mice, suggesting that perforin, which is mainly produced
      by NK cells, is involved in the prevention of vascular damage. Together, these
      findings reveal that NK cells mediate the innate phase of host protection against
      infection with rickettsiae, most likely via IFN-gamma production. Furthermore, NK
      cells are involved in preventing rickettsial infection-induced endothelial cell
      damage, possibly via perforin production.

PMID- 22617215
TI  - The spectroscopic properties of anticancer drug Apigenin investigated by using
      DFT calculations, FT-IR, FT-Raman and NMR analysis.
AB  - The FT-Raman and FT-Infrared spectra of solid Apigenin sample were measured in
      order to elucidate the spectroscopic properties of title molecule in the spectral
      range of 3500-50 cm(-1) and 4000-400 cm(-1), respectively. The recorded FT-IR and
      FT-Raman spectral measurements favor the calculated (by B3LYP/6-31G(d,p) method)
      structural parameters which are further supported by spectral simulation.
      Additional support is given by the collected (1)H and (13)C NMR spectra recorded
      with the sample dissolved in DMSO. The predicted chemical shifts at the B3LYP/6
      31G(d) level obtained using the Gauge-Invariant Atomic Orbitals (GIAO) method
      with and without inclusion of solvent using the Polarizable Continuum Model
      (PCM). By using TD-DFT method, electronic absorption spectra of the title
      compound have been predicted and a good agreement with the TD-DFT method and the
      experimental one is determined. The UV-visible absorption spectra of the compound
      that dissolved in Ethanol, Methanol and DMSO were recorded in the range of 800
      200 nm. The formation of hydrogen bond and the most possible interaction are
      explained using natural bond orbital (NBO) analysis. In addition, the molecular
      electrostatic potential (MEP), frontier molecular orbitals (FMO) analysis and
      atomic charges of the title compound were investigated using theoretical
      calculations. The results are discussed herein and compared with similar
      molecules whenever appropriate.

PMID- 22617216
TI  - Structural and optical properties of nanostructure CdZnO films.
AB  - CdZnO thin films with different ratio of CdO and ZnO (3:1, 1:1, and 1:3) were
      grown on glass substrate using sol-gel spin coating method. The morphology of the
      CdZnO films depends on the amount of ZnO and CdO in the films. The optical band
      gap of the CdZnO films depends on the compositions of CdO and ZnO. Films having
      higher amount of CdO shows the presence of grains along with the fiber nature of
      ZnO, whereas the film with lower percentage of CdO shows fiber nature of the film
      very similar to pure ZnO film. The optical bandgap of CdZnO (3:1), CdZnO (1:1),
      and CdZnO (1:3) films was calculated to be 2.80, 2.49, and 2.52 eV, respectively.
      Other optical properties such as refractive index, extinction coefficient, and
      dielectric constants were calculated using the optical data. The volume and
      surface energy loss functions were also calculated and observed to increase with
      increase in the photon energy.

PMID- 22617217
TI  - Vibration and DFT analysis of 2-methyl-3-nitrophenyl isocyanate and 4-methyl-2
      nitrophenyl isocyanate.
AB  - Vibrational spectra of 2-methyl-3-nitrophenyl isocyanate and 4-methyl-2
      nitrophenyl isocyanate, in the spectral region 4000-100 cm(-1), have been
      measured and assigned. Conformational and harmonic frequency analyses have been
      performed at B3LYP/6-311G(*) level of calculations. The two stable conformers,
      cis and trans, have been computed for each of the molecules. It has been
      determined that the trans conformer has lower energy than the cis by 3.954 kJ/mol
      for 2-methyl-3-nitrophenyl isocyanate; whereas the cis conformer has lower energy
      than the trans by 10.230 kJ/mol for 4-methyl-2-nitrophenyl isocyanate. The
      vibration structure of 2-methyl-3-nitrophenyl isocyanate conforms to the combined
      behavior of its both conformers from which the deviation is shown by the
      structure of 4-methyl-2-nitrophenyl isocyanate which follows only the trans
      conformer. The occurrence of symmetric mode of the methyl group at higher
      frequency near 2944-20 cm(-1) is attributed to the phenyl ring strain caused by
      the substituents. As for the other stretching and bending modes, mutually
      exclusive pattern appears to work for the molecules: The nitro group's non
      coplanarity with the phenyl ring is more evident in 4-methyl-2-nitrophenyl
      isocyanate where the asymmetric mode was assigned to the band at 1569cm(-1),
      whereas the symmetric mode at lower frequency 1339cm(-1). Occasional doublet
      appearance of the strong asymmetric absorption near 2282cm(-1) due to isocyanate
      moiety has been observed in the present study and is assumed to arise from the
      torsional vibration motion of the moiety rendered by the small energy gap between
      the conformers of 2-methyl-3-nitrophenyl isocyanate.

PMID- 22617218
TI  - Facile synthesis and photo-physical properties of cyano-substituted styryl
      derivatives based on carbazole/phenothiazine.
AB  - Four new cyano-substituted styryl derivatives based on carbazole and
      phenothiazine were facilely synthesized by conventional Knoevenagel condensation
      and well characterized. The UV-vis spectra of these dyes showed the lowest-energy
      absorption bands were mainly caused by the HOMO-LUMO one-electron promotion as
      conformed by TD-DFT calculations. The thermogravimetric analysis showed these
      dyes were thermally stable up to 350  degrees C. The UV-vis absorption and
      fluorescence emission spectra were also studied in solvents of different
      polarity, these dyes exhibited unusual large Stokes shift.

PMID- 22617219
TI  - Crystal structure characterization as well as theoretical study of spectroscopic
      properties of novel Schiff bases containing pyrazole group.
AB  - A series of novel Schiff bases containing pyrazole group were synthesized using 1
      aryl-3-methyl-4-benzoyl-5-pyrazolone and phenylenediamine as the starting
      materials. All as-synthesized Schiff bases were characterized by means of NMR, FT
      IR, and MS; and the molecular geometries of two Schiff bases as typical examples
      were determined by means of single crystal X-ray diffraction. In the meantime,
      the ultraviolet-visible light absorption spectra and fluorescent spectra of
      various as-synthesized products were also measured. Moreover, the B3LYP/6-1G(d,p)
      method was used for the optimization of the ground state geometry of the Schiff
      bases; and the spectroscopic properties of the products were computed and
      compared with corresponding experimental data based on cc-pVTZ basis set of TD
      B3LYP method. It has been found that all as-synthesized Schiff bases show a
      remarkable absorption peak in a wavelength range of 270-370 nm; and their maximum
      emission peaks are around 344 nm and 332 nm, respectively.

PMID- 22617220
TI  - Effective fluorescent chemosensors for the detection of Zn2+ metal ion.
AB  - Benzimidazole derivatives synthesized from three components assembling
      condensation reaction behaves as a selective fluorescent sensor for Zn(2+) metal
      ion. These benzimidazole derivatives were characterized by (1)H, (13)C NMR, mass
      and elemental analysis. XRD analysis was carried out for 1-(4-methylbenzyl)-2-p
      tolyl-1H-benzo[d]imidazole. The increase in the fluorescence enhancement can be
      explained on the basis of photo induced electron transfer (PET) mechanism. The
      blockage of the photoinduced electron transfer process from benzimidazole ring to
      aryl fluorophore induced by Zn(2+) co-ordination induced emission enhancement.

PMID- 22617222
TI  - A 3D steady-state model of a tendon-driven continuum soft manipulator inspired by
      the octopus arm.
AB  - Control and modelling of continuum robots are challenging tasks for robotic
      researchers. Most works on modelling are limited to piecewise constant curvature.
      In many cases they neglect to model the actuators or avoid a continuum approach.
      In particular, in the latter case this leads to a complex model hardly
      implemented. In this work, a geometrically exact steady-state model of a tendon
      driven manipulator inspired by the octopus arm is presented. It takes a continuum
      approach, fast enough to be implemented in the control law, and includes a model
      of the actuation system. The model was experimentally validated and the results
      are reported. In conclusion, the model presented can be used as a tool for
      mechanical design of continuum tendon-driven manipulators, for planning control
      strategies or as internal model in an embedded system.

PMID- 22617221
TI  - Solvent effect on the vibrational spectra of Carvedilol.
AB  - Carvedilol (CRV) is an important medicament for heart arrhythmia. The aim of this
      work was the interpretation of its vibrational spectra with consideration on the
      solvent effect. Infrared and Raman spectra were recorded in solid state as well
      in solution. The experimental spectra were evaluated using DFT quantum chemical
      calculations computing the optimized structure, atomic net charges, vibrational
      frequencies and force constants. The same calculations were done for the molecule
      in DMSO and aqueous solutions applying the PCM method. The calculated force
      constants were scaled to the experimentally observed solid state frequencies. The
      characters of the vibrational modes were determined by their potential energy
      distributions. Solvent effects on the molecular properties were interpreted.
      Based on these results vibrational spectra were simulated.

PMID- 22617223
TI  - Vascular effects and electrolyte homeostasis of the natriuretic peptide isolated
      from Crotalus oreganus abyssus (North American Grand Canyon rattlesnake) venom.
AB  - Crotalus oreganus abyssus is a rattlesnake that is usually found in the Grand
      Canyon, United States of America. Knowledge regarding the composition of C. o.
      abyssus venom is scarce. New natriuretic peptides (NPs) have been isolated and
      characterized from the venoms of members of the Crotalinae family. The NP family
      comprises three members, ANP (atrial natriuretic peptide), BNP (b-type
      natriuretic peptide) and CNP (c-type natriuretic peptide), and has an important
      role in blood pressure regulation and electrolyte homeostasis. The aim of the
      present study was to characterize a novel natriuretic-like peptide (Coa_NP2),
      isolated from C. o. abyssus venom. The Coa_NP2 presents an average molecular mass
      of 3419.88Da (theoretical average molecular mass 3418.94Da, monoisotopic
      molecular mass 3416.66Da and theoretical PI 7.78) and its amino acid sequence
      presents the loop region that is characteristic of natriuretic peptides. The
      peptide has 32 amino acids and its complete sequence is
      SYGISSGCFGLKLDRIGTMSGLGCWRLLQDSP. Coa_NP2 is a natriuretic peptide of the ANP/BNP
      like family, since the carboxyterminal region of CNP has its own NP domain. We
      demonstrate, herein, that Coa_NP2 produces a dose-dependent decrease in mean
      arterial pressure in rats, followed by significant increases in concentrations of
      markers of nitric oxide formation measured in the plasma and vasorelaxation in a
      thoracic aortic ring bath. The structural and biological aspects confirm Coa_NP2
      as a new natriuretic peptide, isolated from snake venom.

PMID- 22617224
TI  - Impact of the beta1-adrenoceptor Arg389Gly polymorphism on heart-rate responses
      to bisoprolol and carvedilol in heart-failure patients.
AB  - This pharmacogenetic substudy of the prospective, double-blind, randomized CIBIS
      ELD trial determined the impact of the beta1-adrenoceptor Arg189Gly polymorphism
      on heart-rate responses to bisoprolol or carvedilol in elderly patients with
      heart failure (421 with sinus rhythm, 107 with atrial fibrillation). Patients
      were randomized 1:1 to bisoprolol or carvedilol with a fortnightly dose-doubling
      scheme and guideline target doses. Patients with sinus rhythm responded
      essentially identically to bisoprolol and carvedilol, independent of genotype.
      Atrial fibrillation patients homozygous for Arg389 had a much smaller response to
      carvedilol than carriers of at least one Gly389 allele (mean difference 12 bpm, P
      < 0.00001). Carvedilol up to 2 * 12.5 mg did not reduce heart rate in Arg389Arg
      homozygotes at all. Interestingly, the immediate response to carvedilol did not
      differ between genotypes. The Arg389Gly polymorphism has a major impact on the
      heart-rate response to carvedilol (but not bisoprolol) in patients with heart
      failure plus atrial fibrillation.

PMID- 22617225
TI  - Models for disease progression: new approaches and uses.
AB  - Disease-progression models are useful tools in drug development. They increase
      the information obtained from clinical trials, improve study designs, and allow
      in silico evaluations of new treatment combinations and dose regimens. Disease
      progression modeling can save time and strengthen "go/no-go" criteria. The use of
      meta-based modeling and the linking of disease progression to discrete clinical
      end points have improved the utility of this valuable approach. This article
      provides an overview of disease-progression evaluations using these new
      approaches.

PMID- 22617226
TI  - Effects of CYP induction by rifampicin on tamoxifen exposure.
AB  - Tamoxifen undergoes biotransformation into several metabolites, including
      endoxifen. Differences in metabolism contribute to the interindividual
      variability in endoxifen concentrations, potentially affecting treatment
      efficacy. We evaluated the effects of cytochrome P450 (CYP) induction by
      rifampicin on the exposure levels of tamoxifen and its metabolites and found that
      coadministration of rifampicin resulted in markedly reduced (up to 86%, P <=
      0.040) concentrations of tamoxifen and its metabolites. Given the extensive
      metabolism undergone by tamoxifen, several factors may have contributed to this
      effect. Similar drug-drug interactions may exist between tamoxifen and other
      strong CYP inducers.

PMID- 22617227
TI  - The clinical pharmacogenomics implementation consortium: CPIC guideline for
      SLCO1B1 and simvastatin-induced myopathy.
AB  - Cholesterol reduction from statin therapy has been one of the greatest public
      health successes in modern medicine. Simvastatin is among the most commonly used
      prescription medications. A non-synonymous coding single-nucleotide polymorphism
      (SNP), rs4149056, in SLCO1B1 markedly increases systemic exposure to simvastatin
      and the risk of muscle toxicity. This guideline explores the relationship between
      rs4149056 (c.521T>C, p.V174A) and clinical outcome for all statins. The strength
      of the evidence is high for myopathy with simvastatin. We limit our
      recommendations accordingly.

PMID- 22617228
TI  - Physician assistant and advance practice nurse care in hospital outpatient
      departments: United States, 2008-2009.
AB  - This analysis shows that visits to PAs or APNs have become more common in
      hospital OPDs over the past decade. Several of the 2008-2009 findings are
      consistent with previous studies. For example, visits seen only by a PA or APN
      continue to be higher in rural areas. In addition, a higher proportion of visits
      to PAs or APNs occur with younger patients. This analysis uncovered some new
      findings about PAs or APNs in hospital OPDs. Visits to PAs or APNs are more
      common in nonteaching hospitals and in smaller hospitals. General medical and
      obstetrics or gynecology clinics have higher percentages of PA or APN visits than
      either pediatric or surgery clinics. PAs or APNs in hospital OPDs provide
      services to patients for whom the clinic serves as a primary care provider and
      for assessing new problems or provision of preventive care. PAs or APNs are
      providing an increasing share of care delivered in OPDs compared with the
      previous decade. The findings in this report suggest that PAs or APNs continue to
      provide a critical health care function by providing care in settings with fewer
      physicians, such as rural locations, small hospitals, and nonteaching hospitals.

PMID- 22617229
TI  - Phosphosignature predicts dasatinib response in non-small cell lung cancer.
AB  - Targeted drugs are less toxic than traditional chemotherapeutic therapies;
      however, the proportion of patients that benefit from these drugs is often
      smaller. A marker that confidently predicts patient response to a specific
      therapy would allow an individual therapy selection most likely to benefit the
      patient. Here, we used quantitative mass spectrometry to globally profile the
      basal phosphoproteome of a panel of non-small cell lung cancer cell lines. The
      effect of the kinase inhibitor dasatinib on cellular growth was tested against
      the same panel. From the phosphoproteome profiles, we identified 58
      phosphorylation sites, which consistently differ between sensitive and resistant
      cell lines. Many of the corresponding proteins are involved in cell adhesion and
      cytoskeleton organization. We showed that a signature of only 12 phosphorylation
      sites is sufficient to accurately predict dasatinib sensitivity. Four of the
      phosphorylation sites belong to integrin beta4, a protein that mediates cell
      matrix or cell-cell adhesion. The signature was validated in cross-validation and
      label switch experiments and in six independently profiled breast cancer cell
      lines. The study supports that the phosphorylation of integrin beta4, as well as
      eight further proteins comprising the signature, are candidate biomarkers for
      predicting response to dasatinib in solid tumors. Furthermore, our results show
      that identifying predictive phosphorylation signatures from global, quantitative
      phosphoproteomic data is possible and can open a new path to discovering
      molecular markers for response prediction.

PMID- 22617230
TI  - Total and high-density lipoprotein cholesterol in adults: National Health and
      Nutrition Examination Survey, 2009-2010.
AB  - The percentage of adults aged 20 and over with high total cholesterol has
      declined substantially since 1999-2000. For 2009-2010, the percentage of adults
      with high total cholesterol was 13.4%, thus meeting the Healthy People 2010
      target of 17% or less [Objective (12-14)] (7). Substantial and steady decreases
      in the prevalence of high total cholesterol among men aged 40 and over and women
      aged 60 and over during the 1999-2010 period resulted in achievement of the
      Healthy People 2010 objective in all sex and racial-and-ethnic groups and in all
      sex and age groups except for women aged 40 and over. For 2009-2010, only 11.9%
      of women compared with 31.4% of men aged 20 and over had low HDL cholesterol. The
      percentage with low HDL cholesterol is consistently higher in men than in women
      within each race and ethnicity group. Because women typically have higher HDL
      cholesterol levels than men (6), the percentage with low HDL cholesterol is
      expected to be lower in women than in men. The percentage of adult men with low
      HDL cholesterol is lower in non- Hispanic black men than in Hispanic or non
      Hispanic white men. During 2009-2010, approximately 68% of adults-including 66%
      of men and 70% of women- had their cholesterol checked within the past 5 years.
      These percentages have not changed significantly from 2005-2006, when 65% of men
      and 71% of women had their cholesterol checked within the past 5 years (8).
      Furthermore, the Healthy People 2010 objective for cholesterol screening of at
      least 80% [Objective (12-15)] (7) was not met. Less than one-half of Hispanic men
      were screened within the past 5 years compared with 70% of non-Hispanic white men
      and nearly 62% of non-Hispanic black men. Among U.S. adults in 2009-2010, those
      with adverse concentrations of total cholesterol (15%) and HDL cholesterol (25%)
      are at risk for coronary heart disease, including heart attacks. The U.S.
      Department of Health and Human Services recently announced the Million Hearts
      Initiative (9) with a goal of preventing 1 million heart attacks and strokes over
      the next 5 years. High cholesterol is one major risk factor for heart attacks.

PMID- 22617231
TI  - Seminal plasma proteins in prostatic carcinoma: increased nuclear semenogelin I
      expression is a predictor of biochemical recurrence after radical prostatectomy.
AB  - Semenogelins and eppin are seminal plasma proteins that form a complex and
      inhibit sperm motility. However, the role of these proteins in prostate cancer is
      poorly understood. We immunohistochemically stained for semenogelins I and II and
      eppin in 291 radical prostatectomy specimens. We then evaluated the association
      between their expressions in nuclei, cytoplasms, or intraluminal secretions of
      benign/high-grade prostatic intraepithelial neoplasia/carcinoma cells and
      clinicopathologic profile available for our patient cohort. Stains were positive
      in 32%/77%/84% (nuclear semenogelin I), 87%/94%/84% (nuclear semenogelin II),
      56%/64%/37% (nuclear eppin), 7%/15%/11% (cytoplasmic semenogelin I), 6%/11%/9%
      (cytoplasmic semenogelin II), 68%/74%/95% (cytoplasmic eppin), 97%/98%/13%
      (secreted semenogelin I), 98%/97%/11% (secreted semenogelin II), and 97%/98%/48%
      (secreted eppin) of benign/prostatic intraepithelial neoplasia/carcinoma,
      respectively. The levels of nuclear semenogelin I/cytoplasmic eppin were
      significantly higher in carcinoma than in benign (P<.001/P<.001) or prostatic
      intraepithelial neoplasia (P<.001/P<.001) and in prostatic intraepithelial
      neoplasia than in benign (P<.001/P=.006). Significantly higher nuclear
      semenogelin II expression was found in prostatic intraepithelial neoplasia than
      in benign (P<.001) or carcinoma (P<.001). Significantly lower nuclear eppin
      expression was seen in carcinoma than in benign (P<.001) or prostatic
      intraepithelial neoplasia (P<.001). Secreted semenogelin I, secreted semenogelin
      II, and secreted eppin were all significantly lower in carcinoma than in benign
      (P<.001) or prostatic intraepithelial neoplasia (P<.001). There were no
      statistically significant correlations between each stain and clinicopathologic
      features except significantly lower nuclear eppin expression in Gleason score 8
      or higher tumors. Kaplan-Meier and log-rank tests further revealed that patients
      with nuclear semenogelin I-positive tumor had a significantly higher risk for
      biochemical recurrence (P=.046). Multivariate Cox model showed a trend toward
      significance (P=.093) in nuclear semenogelin I positivity as an independent
      predictor for recurrence. These results suggest that nuclear semenogelin I
      expression could be a reliable prognosticator in men who undergo radical
      prostatectomy.

PMID- 22617232
TI  - Enhanced expression of membrane transporter and drug resistance in keloid
      fibroblasts.
AB  - The mechanisms of keloid resistance to therapy and high recurrence rate remain
      undefined. This study explored the difference in drug resistance between keloid
      and normal fibroblasts. Fibroblasts derived from 9 patients with keloid and 9
      skin donors were randomly combined into 3 keloid cell pools (3 cases per pool)
      and 3 normal cell pools (3 cases per pool) and were compared for their resistance
      to vincristine and mitoxantrone and related molecule expression. The results
      revealed stronger resistance to both vincristine and mitoxantrone with a higher
      survival rate in keloid cells than in normal cells (P<.05). The resistance of
      keloid fibroblasts could be largely abrogated by verapamil treatment. In
      addition, messenger RNA expression levels of multiple-drug resistance-1, ABCB5 (P
      glycoprotein family member), and cytochrome P450 3A4 but not ABCG2 (ATP-binding
      cassette transporter) were significantly higher in passage 1 keloid fibroblasts
      than in passage 1 normal fibroblasts; no significant difference was found in
      latter passages. Immunohistochemistry staining revealed significantly more
      multiple-drug resistance-1-positive cells (round) in keloid tissue than in normal
      skin (mostly spindle shaped) (P<.05) but no significant difference in the
      percentage of positive cells in the 2 groups. Enhanced expression of membrane
      transporters and increased resistance to chemotherapy agents may contribute to
      the keloid's resistance to therapy and the high posttherapy recurrence rate.

PMID- 22617233
TI  - Diagnosis of brain tumors and nuclear medicine imaging.

PMID- 22617234
TI  - Pathological classification of brain tumors.
AB  - The tumors of the central nervous system are classified according to the last
      international classification published by World Health Organization. The
      Classification of Tumors of the Central Nervous System was done on 2007, based on
      morphological features, growth pattern and molecular profile of neoplastic cells,
      defining malignancy grade. The neuropathological diagnosis and the grading of
      each histotype are based on identification of histopathological criteria and
      immunohistochemical data. The histopathology, also consisting of findings with
      prognostic or predictive relevance, plays a critical role in the diagnosis and
      treatment of brain tumors. The recent progresses on radiological, pathological,
      immunohistochemical, molecular and genetic diagnosis improved the
      characterization of brain tumors. Molecular and genetic profiles may identify
      different tumor subtypes varying in biological and clinical behavior. To
      investigate new therapeutic approaches is important to study the molecular
      pathways that lead the processes of proliferation, invasion, angiogenesis,
      anaplastic transformation. Different molecular biomarkers were identified by
      genetic studies and some of these are used in neuro-oncology for the evaluation
      of glioma patients, in particular combined deletions of the chromosome arms 1p
      and 19q in oligodendroglial tumors, methylation status of the O-6 methylguanine-
      DNA methyltransferase gene promoter and alterations in the epidermal growth
      factor receptor pathway in adult malignant gliomas, isocitrate dehydrogenase 1
      (IDH1) and IDH2 gene mutations in diffuse gliomas, as well as BRAF status in
      pilocytic astrocytomas. The prognostic evaluation and the therapeutic strategies
      for patients depend on synthesis of clinical, pathological and biological data:
      histological diagnosis, malignancy grade, gene-molecular profile, radiological
      pictures, surgical resection and clinical findings (age, tumor location,
      "performance status").

PMID- 22617235
TI  - CT and MRI of brain tumors.
AB  - Imaging plays a crucial role in the management of patients with brain tumors. The
      technical improvement of computed tomography (CT) and magnetic resonance (MRI)
      with the development of, new imaging techniques strongly improved the detection
      and characterization of brain tumors. For the optimal therapeutic management of
      the oncologic patient not only the recognition of the lesion is needed, but also
      the exclusion of other diseases that can mimic brain tumors. The preoperative
      assessment of malignancy and of relationships of the tumor with surrounding
      eloquent structures are also necessary to allow the correct choice of therapy and
      to warn surgeons of possible risks of the surgical approach. This article is an
      overview of the current state of neuroimaging of the most frequent brain tumors
      including CT and MRI, perfusion weighted imaging (PWI), diffusion weighted
      imaging (DWI), diffusion tensor imaging (DTI), proton magnetic resonance
      spectroscopy (1H-MRS) and functional MRI based on blood oxygen level (fMRI BOLD).
      Indeed, in the last years, a transition took place from a purely anatomy-based
      radiology to one that incorporates functional, hemodynamic, metabolic, cellular,
      and cytoarchitectural alterations. Neuroimaging has evolved into a comprehensive
      diagnostic tool that allows the characterization of morphologic as well as
      biologic alterations to diagnose and grade brain tumors and to monitor and assess
      treatment response and patient prognosis.

PMID- 22617236
TI  - 18F-FDG-PET/CT.
AB  - [18F]FDG has been the first radiopharmaceutical used for human brain PET studies
      and still is the most used radiotracer worldwide for PET and PET/CT oncologic
      applications. In the assessment of brain tumors, in spite of its low sensitivity
      in some histological exams, chiefly low-grade lesions, its prognostic value
      remains of high clinical impact. Moreover, the reliability of [18F]FDG in
      examining not only the tumor itself, but also the functional state of the whole
      brain, makes this tracer a valuable tool for treatment decisions and patient
      management, even nowadays when new tracers (especially amino-acids) are
      available. In addition, [18F]FDG has a role in the differential diagnosis between
      relapse and necrosis when assessing aggressive tumors and to establish
      dedifferentiation in low-grade lesions. With the growing of available therapies,
      another emerging application of [18F]FDG is the monitoring of response to
      treatment, even though more evidence is needed to assess the best scanning time.
      Finally, the implementation of CT in PET devices most likely will improve the
      sensitivity and specificity of [18F]FDG, even though more data are needed to
      better understand which is the real advantage of PET/CT with respect to
      multimodality imaging. Currently, the possible added value of PET/CT is in the
      study of secondary brain lesions. It is believable that in the future we will
      keep on speaking about this "old" radiotracer, still alive.

PMID- 22617237
TI  - PET with radiolabeled aminoacid.
AB  - Since the clinical introduction of FDG, neuroimaging has been the first area of
      PET application in oncology. Later, while FDG-PET became progressively a key
      imaging modality in the management of the majority of malignancies outside the
      brain, its neuro-oncologic indications faced some limitations because of the
      unfavourable characteristics of FDG as brain tumor-seeking agent. PET
      applications in neuro-oncology have received new effectiveness by the advent of
      positron-emission labelled amino acids, so that it has been coined the term
      "Amino acid PET" to differentiate this imaging tool from FDG-PET. Radiolabeled
      amino acids are a very interesting class of PET tracers with great diagnostic
      potential in neuro-oncology because of their low uptake in normal brain and,
      conversely, high uptake in most brain tumors including low-grade gliomas. The
      present article surveys the results obtained using L-[methyl-11C]Methionine
      (MET), that has been the ancestor of PET amino acid tracers and is still the most
      popular amino acid imaging modality in oncology, and stresses the important role
      that this diagnostic modality can play in the evaluation of brain tumors.
      However, the use of MET is restricted to PET centers with an in-house cyclotron
      and radiochemistry facility, because of the short half-life (20 min) of 11C. The
      promising results of MET have stimulated the development of 18F-labelled
      aminoacid tracers, particularly O-(2-18F-fluoeoethyl1)-L-tyrosine (FET), that has
      the same properties of MET and, thanks to the longer half-life of 18F (about 110
      min), allows a distribution strategy from a production tracer site to user
      satellite PET centers. Considering a more widespread use of Amino acid PET,
      together with the recent development of integrated PET-MRI imaging systems, and
      the oncoming clinical validation of other interesting PET tracers, i.e. FMISO or
      18F-FAZA for hypoxia imaging and FLT for tumor proliferation imaging, it can be
      reasonably expected that metabolic imaging with PET is close to becoming a key
      diagnostic modality in the management of brain tumors, as has already been for
      Total Body FDG-PET/CT in extra-brain oncology.

PMID- 22617238
TI  - PET and SPECT for radiation treatment planning.
AB  - Positron emission tomography (PET) and single photon computed emission tomography
      (SPECT) have been evaluated in several studies for radiation treatment planning
      in patients with primary brain tumors. PET with the glucose analogue
      fluorodeoxyglucose has been found to be of limited use for radiation treatment
      planning because the high physiologic glucose use of normal gray matter makes
      delineation of tumors challenging. In contrast, there is considerable evidence
      that PET or SPECT with radiolabeled amino acid or amino acid analogues provides
      valuable information for the delineation of gliomas. Increased amino acid uptake
      has been found to be a more specific marker for viable tumor tissue than signal
      abnormalities on MRI. In addition, increased amino acid uptake is frequently
      observed in tumor areas that have not caused a disruption of the blood brain
      barrier. Therefore, PET and SPECT with radiolabeled amino acids provide a unique
      opportunity to visualize the infiltrative growth of gliomas and use this
      information for radiation treatment planning.

PMID- 22617239
TI  - New PET radiopharmaceuticals beyond FDG for brain tumor imaging.
AB  - Brain tumors have a relatively high incidence (>14/100000 people/year) and
      represent a major cause of death in the population. The direct and indirect costs
      of brain tumors are high in the developed countries (5.2 bn EUR/year in the EU;
      4.46 bn USD/year in the US). A combination of recent advancements in molecular
      neuroimaging, with positron emission tomography (PET) in the first place,
      providing clinicians with an improved diagnostic and therapy follow-up efficacy,
      novel approaches in the field of neurosurgery (including neuronavigation,
      intraoperative control of the nervous function, tumor histology and volume), and
      developments in treatment strategies (including new chemotherapeutics and new
      targeted agents, immunotherapies, sophisticated irradiation protocols) has in the
      past years improved the survival of brain tumor patients. A major component of
      further improvements is related to advancements in the development of novel
      molecular imaging biomarkers for brain tumor detection, including new PET
      radiopharmacons with high specificity, sensitivity and diagnostic accuracy.
      Despite the fact that FDG is the "working horse" of brain tumor imaging with PET
      and well over 90 % of diagnostic imaging studies in neuro-oncology are made with
      FDG world-wide, due to its sub-optimal specificity and sensitivity the search for
      non-FDG brain tumor PET radiotracers has been intensifying during the past decade
      in order to improve the diagnostic sensitivity, specificity and accuracy of
      molecular imaging of brain tumors. The most promising non-FDG brain tumor
      radiotracers include radioactively labeled nucleoside and amino acid analogues,
      tracers of oxidative metabolism, fatty acid metabolism and hypoxia, as well as
      receptor ligands of various kinds. The most widely tested non-FDG radiotracers
      include [11C]methionine (MET), [18F]fluorothymidine (FLT), [18F]fluoroethyl-l
      tyrosine (FET), [18F]fluoro-alpha-methyltyrosine (FMT), [18F]fluoromisonidazole
      (F-MISO), 6-[18F]fluoro-dihydroxy-l-phenylalanine (F-DOPA), [11C]choline (CHO)
      and [18F]choline. The selective advantages of these radiotracers, compared to
      FDG, are varying, MET and FET appearing to be the most useful dedicated glioma
      radiotracers. Nevertheless, several other non-metabolic radiopharmaceuticals are
      also being tested or are in the validation phase. Although novel dedicated
      radiotracer candidates should offer an increased selectivity, specificity and
      diagnostic accuracy when compared to the recently existing brain tumor tracers, a
      dual or a multitracer approach may still offer the optimal solution in brain
      tumor imaging with PET in the near future.

PMID- 22617240
TI  - Stage III non-small-cell lung cancer: population-based patterns of treatment in
      British Columbia, Canada.
AB  - INTRODUCTION: Management of Stage III non-small-cell lung cancer (NSCLC) involves
      surgery, radiotherapy (RT), chemotherapy, and best supportive care. The aims were
      to describe the patterns of treatment in a population-based cohort of patients,
      and compare utilization of RT and chemotherapy to model estimates of need.
      METHODS: Patients diagnosed with Stage III NSCLC between January 1, 2000, to
      December 31, 2007, were identified from the British Columbia Cancer Agency
      database. Patients who had prior or concomitant malignancy were excluded. Patient
      demographics, tumor characteristics, and initial treatment were extracted.
      Survival data were derived from the British Columbia Vital Statistics Death
      Listings. RESULTS: 2365 patients with Stage III NSCLC were referred, of which 212
      patients were excluded, leaving 2153 patients in the study population. Median age
      was 69 years. Disease stage was IIIA in 49% and IIIB in 51%. Histologies were
      squamous-cell carcinoma (31%), adenocarcinoma (27%), NSCLC not otherwise
      specified (31%), and other pathology (11%). Initial treatment included surgery in
      12%, RT in 78%, and chemotherapy in 31%. Predicted RT utilization was 77% to 87%
      and chemotherapy 78%. From 2000 to 2007, curative-intent treatment increased from
      21% to 35%, chemoradiotherapy from 8% to 18.6%, and concurrent chemoradiotherapy
      from 5.1% to 17.6%. Median survival was 30 months for patients who had curative
      surgery, 21 months for curative RT, 8 months for palliative treatment, and 5
      months for best supportive care (p < 0.001). CONCLUSION: RT utilization was
      similar to that predicted by models whereas chemotherapy utilization was less.
      During the study period, the proportion of patients receiving curative
      chemoradiotherapy doubled and of those receiving concurrent chemoradiotherapy
      trebled.

PMID- 22617241
TI  - Lymphovascular invasion in non-small-cell lung cancer: implications for staging
      and adjuvant therapy.
AB  - BACKGROUND: Lymphovascular space invasion (LVI) is an established negative
      prognostic factor and an indication for postoperative radiation therapy in many
      malignancies. The purpose of this study was to evaluate LVI in patients with
      early-stage non-small-cell lung cancer, undergoing surgical resection. METHODS:
      All patients who underwent initial surgery for pT1-3N0-2 non-small-cell lung
      cancer at Duke University Medical Center from 1995 to 2008 were identified. A
      multivariate ordinal regression was used to assess the relationship between LVI
      and pathologic hilar and/or mediastinal lymph node (LN) involvement. A
      multivariate Cox regression analysis was used to evaluate the relationship of LVI
      and other clinical and pathologic factors on local failure (LF), freedom from
      distant metastasis (FFDM), and overall survival (OS). Kaplan-Meier methods were
      used to generate estimates of LF, FFDM, and OS in patients with and without LVI.
      RESULTS: One thousand five hundred and fifty-nine patients were identified. LVI
      was independently associated with the presence of regional LN involvement (p <
      0.001) along with lobar (versus sublobar) resections (p < 0.001), and an open
      thoracotomy (versus video-assisted thoracoscopic surgery). LVI was not
      independently associated with LF on multivariate analysis (hazard ratio [HR] =
      1.23, p = 0.25), but was associated with a lower FFDM (HR 1.52, p = 0.005) and OS
      (HR 1.26, p = 0.015). In addition, multivariate analysis showed that LVI was
      strongly associated with increased risk of developing distant metastases (HR =
      1.75, p = 0.006) and death (HR = 1.53, p = 0.003) in adenocarcinomas but not in
      squamous carcinomas. CONCLUSIONS: LVI is associated with an increased risk of
      harboring regional LN involvement. LVI is also an adverse prognostic factor for
      the development of distant metastases and long-term survival.

PMID- 22617242
TI  - Cause-specific mortality in relation to chrysotile-asbestos exposure in a Chinese
      cohort.
AB  - INTRODUCTION: The carcinogenic potency of chrysotile asbestos remains a
      contentious topic, and more data are needed to address this issue. We examine
      cause-specific mortality, especially lung cancer, and its association with
      chrysotile-asbestos exposure in a Chinese cohort. METHODS: A cohort of 577
      workers from a chrysotile-textile plant was followed prospectively from 1972 to
      2008. Occupational history, exposure information, and smoking data were obtained
      from company records and personal interviews; vital status and causes of death
      were ascertained from death registries and hospitals. Workers were classified
      into three exposure levels on the basis of exposure assessments of different
      workshops. Standardized Mortality Ratios (SMRs) were calculated in terms of
      exposure levels and other indices. RESULTS: Among 259 identified deaths, 53 died
      from lung cancer, with an SMR of 4.08 (95% confidence interval 3.12, 5.33), and
      96 from all cancers with an SMR of 2.09 (1.71, 2.55). In addition, two deaths
      from mesothelioma were observed. Increased mortality from respiratory diseases
      was also observed (SMR 3.38, 95% confidence interval 2.72, 4.21). Asbestos
      exposure levels, exposure years, and birth cohorts showed a clear trend of risk
      for lung cancer and respiratory diseases. CONCLUSION: The current analysis
      indicated that exposure to chrysotile asbestos was closely associated with excess
      mortality from lung cancer and respiratory diseases.

PMID- 22617243
TI  - Characterization of lymphomas developing in immunodeficient mice implanted with
      primary human non-small cell lung cancer.
AB  - INTRODUCTION: Xenograft models of epithelial malignancies potentially have
      greater correlation with clinical end points. We implanted 153 primary non-small
      cell lung carcinomas into non-obese diabetic-severe combined immunodeficient mice
      to develop primary lung cancer xenografts. Sixty-three xenografts formed.
      However, in 19 implantations, tumors consisted of a lymphocyte proliferation
      without a carcinoma component. We further characterized these lymphomas to
      determine clinicopathological features associated with their formation. METHODS:
      Lymphomas were investigated morphologically and by silver in situ hybridization
      to determine their species of origin. Characterization both of the xenograft
      lymphomas and the primary NSCLCs from which they were derived included
      immunohistochemistry for lymphoma markers and Epstein Barr virus Early RNA (EBER)
      by in situ hybridization. DNA was profiled using the MassARRAY platform; EML4-ALK
      translocations and lymphocyte infiltration were assessed in the primary tumor.
      Lymphoma formation was correlated with patient and primary tumor characteristics
      and survival. RESULTS: The lymphocytic tumors were EBER positive, human diffuse
      large B-cell lymphomas (DLBCLs). Significantly more DLBCLs that formed in mice
      arose in primary lung adenocarcinomas and in epithelial growth factor receptor
      mutant never smokers. DLBCL formation was not associated with the degree of tumor
      infiltrating lymphocytes or EBER-positive lymphocytes in the primary NSCLCs.
      Patients whose tumors developed DLBCL had longer disease-free survival compared
      with patients whose tumors formed epithelial xenografts (hazard ratio: 0.44; 95%
      confidence interval: 0.18 -1.06, Wald p = 0.07), regardless of genotype.
      CONCLUSION: We hypothesize that mechanisms involved in the active suppression of
      viral antigens may also be involved in the suppression of tumor antigens, and may
      have resulted in the observed favorable clinical outcome.

PMID- 22617244
TI  - High SUVmax on FDG-PET indicates pleomorphic subtype in epithelioid malignant
      pleural mesothelioma: supportive evidence to reclassify pleomorphic as
      nonepithelioid histology.
AB  - BACKGROUND: We have recently proposed to reclassify the pleomorphic subtype of
      epithelioid malignant pleural mesothelioma (MPM) as nonepithelioid
      (biphasic/sarcomatoid) histology because of its similarly poor prognosis. We
      sought to investigate whether preoperative maximum standardized uptake value
      (SUVmax) on F-fluorodeoxyglucose (FDG) positron emission tomography (PET)
      correlates with histologic subtype in MPM. METHODS: Clinical data were collected
      for 78 patients with MPM who underwent preoperative FDG-PET. We retrospectively
      classified the epithelioid tumors into five subtypes: trabecular,
      tubulopapillary, micropapillary, solid, and pleomorphic. Tumors were categorized
      by SUVmax into two groups: low (<10.0) and high (>=10.0). RESULTS: The median
      overall survival of epithelioid tumors with high SUVmax (n = 12) was
      significantly shorter (7.1 months) than that of epithelioid tumors with low
      SUVmax (n = 54, 18.9 months, p < 0.001) and comparable to nonepithelioid tumors
      (n = 12, 7.2 months). Epithelioid tumors with pleomorphic subtype (n = 9) had
      marginally higher SUVmax (mean +/- SD: 10.6 +/- 5.9) than epithelioid
      nonpleomorphic subtype (n = 57, 6.5 +/- 3.2, p = 0.050), and were comparable to
      that of nonepithelioid tumors (n = 12, 9.1 +/- 4.8). Among the epithelioid tumors
      with high SUVmax (n = 12), 50% (n = 6) showed pleomorphic subtype. In contrast,
      among epithelioid tumors with low SUVmax (n = 54), 6% (n = 3) showed epithelioid
      pleomorphic subtypes (p = 0.001). A positive correlation between mitotic count
      and SUVmax was observed (r = 0.30, p = 0.010). CONCLUSIONS: Pleomorphic subtype
      of epithelioid MPM showed higher SUVmax than the epithelioid nonpleomorphic
      subtype and was similar to nonepithelioid histology. Preoperative SUVmax on FDG
      PET in epithelioid MPM can indicate patients with pleomorphic subtype with poor
      prognosis, supporting their reclassification as nonepithelioid.

PMID- 22617246
TI  - Increased circulating miR-625-3p: a potential biomarker for patients with
      malignant pleural mesothelioma.
AB  - INTRODUCTION: We investigated the ability of cell-free microRNAs (miRNAs) in
      plasma and serum to serve as a biomarker for malignant mesothelioma (MM).
      METHODS: Using miRNA microarrays, we profiled plasma samples from MM patients and
      healthy controls. miRNAs with significantly different abundance between cases and
      controls were validated in a larger series of MM patients and in an independent
      series of MM patients using quantitative real-time polymerase chain reaction.
      Levels of candidate miRNAs were also quantified in MM tumor samples. RESULTS: We
      compared cell-free miRNA profiles in plasma from MM patients with healthy
      controls. Reviewing 90 miRNAs previously reported to be associated with MM, we
      found that the levels of two miRNAs, miR-29c* and miR-92a, were elevated in
      plasma samples from MM patients. In addition, we identified 15 novel miRNAs
      present at significantly higher levels in the plasma of MM patients. Further
      analysis of candidate miRNAs by real time-quantitative polymerase chain reaction
      confirmed that one of them, miR-625-3p, was present in significantly higher
      concentration in plasma/serum from MM patients and was able to discriminate
      between cases and controls, in both the original and the independent series of
      patients. MiR-625-3p was also found to be up-regulated in tumor specimens from a
      group of 18 MM patients, who underwent extrapleural pneumonectomy. CONCLUSION:
      Our data confirm the potential of miR-29c* and miR-92a as candidate tumor markers
      and reveal that miR-625-3p is a promising novel diagnostic marker for MM.

PMID- 22617245
TI  - Preclinical rationale for use of the clinically available multitargeted tyrosine
      kinase inhibitor crizotinib in ROS1-translocated lung cancer.
AB  - INTRODUCTION: Most clinically available small-molecule kinase inhibitors are
      multi-targeted and can inhibit multiple kinases. Our driving hypothesis was that
      one of these multi-targeted tyrosine kinase inhibitors (TKIs) would have
      antiproliferative activity against ROS1 translocated non-small-cell lung cancer
      (NSCLC). METHODS: We selected NSCLC cell lines--A549 (KRAS G12S), NCI-H3255 (EGFR
      L858R), NCI-H3122 (EML4-ALK E13;A20), and HCC78 (SLC34A2-ROS1)-to evaluate the
      antiproliferative effects of submicromolar concentrations of the multitargeted
      TKIs imatinib, sorafenib, erlotinib, and crizotinib. RESULTS: Imatinib and
      sorafenib were unable to significantly inhibit proliferation of the
      aforementioned cell lines. Erlotinib only inhibited EGFR mutated NCI-H3255, as
      expected. Crizotinib displayed dose-dependent inhibition of anaplastic lymphoma
      kinase translocated NCI-H3122 and also ROS1--translocated HCC78. The SLC34A2-ROS1
      translocated HCC78 cell line had phosphorylated levels of ROS1, AKT, and ERK
      inhibited by submicromolar doses of crizotinib, and subsequently underwent
      apoptosis. CONCLUSIONS: The ROS1-translocated HCC78 cell line was sensitive to
      inhibition by the multitargeted ALK/MET/RON/ROS1 inhibitor crizotinib.
      Preclinical data supports the clinical development of crizotinib for ROS1
      translocated NSCLC.

PMID- 22617247
TI  - Effect of chemotherapy in patients with resected small-cell or large-cell
      neuroendocrine carcinoma.
AB  - INTRODUCTION: Surgical resection of an undiagnosed lung lesion may lead to
      unintentional removal of small-cell lung cancer (SCLC). The benefit of
      perioperative chemotherapy in resected SCLC or large-cell neuroendocrine
      carcinomas (LCNEC) is not clear. METHODS: This retrospective analysis included
      limited disease SCLC and LCNEC that had been surgically removed between 1979 and
      2007 at a single institution. Perioperative treatments were analyzed, and
      survival followed up. Log rank tests were used to compare overall survival.
      RESULTS: Among 74 patients who had a tumor resection, 45 received chemotherapy,
      four had preoperative radiotherapy, and 21 had postoperative radiotherapy. Eleven
      patients were women. The median age was 64 in the surgery group and 58 in the
      surgery plus chemotherapy group, and four and 11 patients in these groups,
      respectively, had LCNEC. There were 10 node positive tumors and only two
      incomplete resections in the surgery group versus 27 node positive tumors and
      three incomplete resections in the surgery plus chemotherapy group. The median
      follow-up was shorter in the group with surgery alone: 4.5 years (1.4-7) versus
      5.8 years (0.6-19.6). Among the patients with a survival or a follow-up of at
      least 6 months, the median survival was 2.3 and 6.1 years in the surgery (n = 20)
      and surgery plus chemotherapy (n = 39) groups, respectively, such that the hazard
      ratio for death was 0.48 (95% confidence interval, 0.24-0.99, p = 0.04).
      CONCLUSION: These results suggest that perioperative chemotherapy may be
      beneficial in patients with resected SCLC or LCNEC.

PMID- 22617248
TI  - The relationship between volume or surgeon specialty and outcome in the surgical
      treatment of lung cancer: a systematic review and meta-analysis.
AB  - BACKGROUND: Whether improvement of quality of surgical cancer care can be
      achieved by centralizing care in high-volume specialized centers is a subject of
      ongoing debate. We have conducted a meta-analysis of the literature on the effect
      of procedural volume or surgeon specialty on outcome of lung resections for
      cancer. METHODS: A systematic search of articles published between January 1,
      1990 and January 20, 2011 on the effects of surgeon specialty and hospital or
      surgeon volume of lung resections on mortality and survival was conducted. After
      strict inclusion, meta-analysis assuming a random-effects model was performed.
      Meta-regression was used to identify volume cutoff values. Heterogeneity and the
      risk of publication bias were evaluated. RESULTS: Nineteen relevant studies were
      found. Studies were heterogeneous, especially in defining volume categories. The
      pooled estimated effect size was significant in favor of high-volume hospitals
      regarding postoperative mortality (odds ratio [OR] 0.71; confidence interval 0.62
      0.81), but not for survival (OR 0.93; confidence interval 0.84-1.03). Surgeon
      volume showed no significant effect on outcome. General surgeons had
      significantly higher mortality risks than general thoracic (OR 0.78; 0.70-0.88)
      or cardiothoracic surgeons (OR 0.82; 0.69-0.96). A minimal annual volume of
      resections for lung cancer could not be identified. CONCLUSIONS: Hospital volume
      and surgeon specialty are important determinants of outcome in lung cancer
      resections, but evidence-based minimal-volume standards are lacking. Evaluation
      of individual institutions in a national audit program might help elucidate the
      influence of individual quality-of-care parameters, including hospital volume, on
      outcome.

PMID- 22617249
TI  - Aldehyde dehydrogenase 1A1 possesses stem-like properties and predicts lung
      cancer patient outcome.
AB  - INTRODUCTION: Lung cancer contains a small population of cancer stem cells that
      contribute to its initiation and progression. We investigated the biological
      function and clinical significance of aldehyde dehydrogenase 1A1 (ALDH1A1) in non
      small-cell lung carcinoma (NSCLC). METHODS: ALDH1A1 assay or small interfering
      RNA transfection was employed to isolate ALDH1A1+ cells or knock down ALDH1A1
      expression in H2087 cells, respectively. Biological functions of ALDH1A1+ and
      ALDH1A1 silenced cells were investigated using in vitro and in vivo methods.
      ALDH1A1 expression was analyzed using immunohistochemistry on tissue microarrays
      with 179 lung cancer tissues and 26 normal lung tissues. RESULTS: The abilities
      of clone formation, proliferation, cell growth, and migration were increased in
      ALDH1A1+ and ALDH1A1 silenced cells. ALDH1A1+ lung cancer cells initiated tumors
      that resembled the histopathologic characteristics and heterogeneity of the
      parental lung cancer cells in mice. The silencing of ALDH1A1 expression in H2087
      lung cancer cells inhibited cell proliferation and migration significantly.
      ALDH1A1 was expressed in 42% of normal lung tissues (11 of 26), with strong
      expression in the basal cells and globular cells of the normal bronchus and weak
      expression in the alveolar epithelial cells. Compared with normal lung tissues,
      45% of NSCLC samples (81 of 179) were read as positive for ALDH1A1. Positive
      ALDH1A1 expression was correlated with patients' smoking status (p = 0.022),
      lymph-node metastasis (p = 0.006), clinical stage (p = 0.004), and a decreased
      overall survival time (p < 0.001). Positive ALDH1A1 expression in lung cancer
      tissues was an independent prognostic factor for NSCLC (odds ratio = 5.232, p <
      0.001). CONCLUSION: Elucidating the biological functions of ALDH1A1 could be
      helpful in studying lung tumorigenesis and for developing new therapeutic
      approaches.

PMID- 22617251
TI  - Sentinel node status predicts survival in thick melanomas: the Oxford
      perspective.
AB  - AIMS: To determine the prognostic value of SLNB in patients with thick melanoma
      in terms of overall survival (OS) and recurrence-free survival (RFS). METHODS:
      136 patients with primary tumours (Breslow thickness >= 4.0 mm) underwent SLNB.
      OS and RFS were calculated and a multivariate Cox regression model used to
      determine the important prognostic factors for predicting OS and RFS. RESULTS:
      Median Breslow thickness was 5.5 mm and 60% were ulcerated. Median follow up was
      4 years (95% CI = 4-5) with 54 patients having died at the time of analysis. 5
      year OS for SLNB positive patients was 32%, compared to 78% for negative
      patients. The significant predictors of poorer OS were increasing age (p = 0.03),
      increasing Breslow thickness (p = 0.03) and SLNB positivity (p < 0.0001). 5 year
      RFS was significantly worse in the SLNB positive population compared to the
      negative patients (p < 0.0001); 27% versus 66% respectively. CONCLUSIONS:
      Patients with a thick melanoma and a positive SLNB have a significantly worse RFS
      and OS compared to those with a negative SLNB. Over three-quarters of patients
      with a negative SLNB survived five years. These findings have implications for
      the subpopulations included in adjuvant therapy trials and we advocate SLNB be
      recommended in patients with thick melanomas.

PMID- 22617250
TI  - C-Met inhibitor MK-8003 radiosensitizes c-Met-expressing non-small-cell lung
      cancer cells with radiation-induced c-Met-expression.
AB  - INTRODUCTION: The radiation doses used to treat unresectable lung cancer are
      often limited by the proximity of normal tissues. Overexpression of c-Met, a
      receptor tyrosine kinase, occurs in about half of non-small-cell lung cancers
      (NSCLCs) and has been associated with resistance to radiation therapy and poor
      patient survival. We hypothesized that inhibiting c-Met would increase the
      sensitivity of NSCLC cells to radiation, enhancing the therapeutic ratio, which
      may potentially translate into improved local control. METHODS: We tested the
      radiosensitivity of two high-c-Met-expressing NSCLC lines, EBC-1 and H1993, and
      two low-c-Met-expressing lines, A549 and H460, with and without the small
      molecule c-Met inhibitor MK-8033. Proliferation and protein expression were
      measured with clonogenic survival assays and Western blotting, respectively.
      gamma-H2AX levels were evaluated by immunofluorescence staining. RESULTS: MK-8033
      radiosensitized the high-c-Met-expressing EBC-1 and H1993 cells but not the low-c
      Met-expressing cell lines A549 and H460. However, irradiation of A549 and H460
      cells increased the expression of c-Met protein at 30 minutes after the
      irradiation. Subsequent targeting of this up-regulated c-Met by using MK-8033
      followed by a second radiation dose reduced the clonogenic survival of both A549
      and H460 cells. MK-8033 reduced the levels of radiation-induced phosphorylated
      (activated) c-Met in A549 cells. CONCLUSIONS: These results suggest that
      inhibition of c-Met could be an effective strategy to radiosensitize NSCLC tumors
      with high basal c-Met expression or tumors that acquired resistance to radiation
      because of up-regulation of c-Met.

PMID- 22617253
TI  - Noxious stimulation attenuates ketamine-induced neuroapoptosis in the developing
      rat brain.
AB  - BACKGROUND: Ketamine induces neuroapoptosis in neonatal rodents. However, these
      experimental paradigms were performed without concurrent noxious stimulation, a
      condition that does not reflect the interaction of anesthesia and surgical
      stimulation. Noxious stimulation with and without concurrent analgesic drugs has
      been shown to have divergent patterns of neuronal activation and cell death. We
      hypothesized that concurrent noxious stimulation would attenuate ketamine-induced
      caspase-3 activation. METHODS: Postnatal day 7 Sprague-Dawley rat pups were
      randomized to a 6-h exposure to ketamine with and without peripheral noxious
      stimulation by intraplantar injection of complete Freund's adjuvant. A cohort of
      naive rat pups with and without complete Freund's adjuvant injections served as
      control subjects. Neuroapoptosis was measured by cleaved caspase-3 expression and
      terminal deoxynucleotidyl-transferase mediated 2'-deoxyuridine 5'-triphosphate
      nick end labeling staining. In order to determine if concurrent noxious
      simulation altered the expression of cell survival and cell cycle proteins,
      levels of protein kinase B and glycogen synthase kinase-3beta and cyclin D1 were
      measured. RESULTS: Ketamine induced a significant increase in cleaved caspase-3
      expression and terminal deoxynucleotidyl-transferase mediated 2'-deoxyuridine 5'
      triphosphate nick end labeling staining with increases in cyclin D1 levels.
      Concurrent noxious stimulation with ketamine attenuated caspase-3 activation and
      maintained cyclin D1 levels. Phosphorylation of protein kinase B and glycogen
      synthase kinase-3beta was not definitively altered under these conditions.
      CONCLUSION: The administration of ketamine with concurrent noxious stimulation
      results in the attenuation of the neuroapoptotic response. These findings suggest
      that concurrent surgery and procedural pain attenuates ketamine-induced
      neuroapoptosis.

PMID- 22617254
TI  - Expression of complement component C7 and involvement in innate immune responses
      to bacteria in grass carp.
AB  - Activation of the complement system, which forms a major part of the innate
      immune system, results in the formation of the terminal complement complex. The
      complement component, C7, plays an integral role in the assembly of this complex
      within target cell membranes. In this study, C7 was isolated and characterized
      from grass carp, an important cultured fish in China. The predicted amino acid
      sequence of C7 cDNA (2644 bp) exhibited 55.4 and 48.3% homology with trout C7-1
      and zebrafish C7, respectively. The grass carp C7 gene was consisted of 18 exons
      and 17 introns. C7 gene expression was detected in the trunk kidney, liver, head
      kidney, skin, spleen, heart and intestine. Significant changes in C7 transcript
      expression (>20-fold) were detected following Aeromonas hydrophila infection,
      indicating C7 involvement in innate immune responses to bacteria in teleost fish.

PMID- 22617252
TI  - Gene expression in skin, muscle, and dorsal root ganglion after plantar incision
      in the rat.
AB  - BACKGROUND: Treating postoperative pain remains a significant challenge for
      perioperative medicine. Recent studies have shown that nerve growth factor is up
      regulated and contributes to incisional pain. To date, few studies have examined
      expression of other neurotrophin-related mediators that may contribute to the
      development and/or maintenance of incisional pain. METHODS: Male Sprague-Dawley
      rats underwent a plantar incision, and pain behaviors were examined (n = 6). In a
      separate group of rats, expression of neurotrophic factors were studied. At
      various times after incision (n = 4) or sham surgery (n = 4), the skin, muscle,
      and dorsal root ganglia were harvested and total RNA isolated. Real-time reverse
      transcription polymerase chain reaction was performed and the fold change in gene
      expression was analyzed using significance analysis of microarrays. RESULTS:
      Several genes were changed (P < 0.05) as early as 1 h after incision. Expression
      of artemin and nerve growth factor were increased in both incised skin and
      muscle. Brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-5
      were all down-regulated in the skin but up-regulated in the muscle 48 h after
      incision. Few genes changed in the dorsal root ganglion. Most changes in
      expression occurred in the first 48 h after incision, a timeframe when pain
      behavior was the greatest. CONCLUSION: Surgical incision is associated with pain
      related gene expression changes in skin, muscle, and, to a lesser extent, dorsal
      root ganglion. The gene expression profile provides clues as to mediators that
      are involved in peripheral sensitization and pain transmission after surgical
      incision and also suggest mechanisms for resolution of postoperative pain when
      more persistent pain syndromes like neuropathic pain continue.

PMID- 22617257
TI  - An ultrasensitive electrochemical impedance sensor for a special BRCA1 breast
      cancer gene sequence based on lambda exonuclease assisted target recycling
      amplification.
AB  - A label-free, target recycling electrochemical impedance spectroscopy (EIS) DNA
      sensor has been developed for detection of a model related to the BRCA1 breast
      cancer gene with a detection limit of 0.05 nM.

PMID- 22617256
TI  - A p.C343S missense mutation in PJVK causes progressive hearing loss.
AB  - Mutations in PJVK, encoding Pejvakin, cause autosomal recessive nonsyndromic
      hearing loss in humans at the DFNB59 locus on chromosome 2q31.2. Pejvakin is
      involved in generating auditory and neural signals in the inner ear. We have
      identified a consanguineous Pakistani family segregating sensorineural
      progressive hearing loss as a recessive trait, consistent with linkage to DFNB59.
      We sequenced PJVK and identified a novel missense mutation, c.1028G>C in exon 7
      (p.C343S) co-segregating with the phenotype in the family. The p.C343 residue is
      fully conserved among orthologs from different vertebrate species. We have also
      determined that mutations in PJVK are not a common cause of hearing loss in
      families with moderate to severe hearing loss in Pakistan. This is the first
      report of PJVK mutation in a Pakistani family and pinpoints an important residue
      for PJVK function.

PMID- 22617258
TI  - On the evolution of personalities via frequency-dependent selection.
AB  - Personality differences can be found in a wide range of species across the animal
      kingdom, but why natural selection gave rise to such differences remains an open
      question. Frequency-dependent selection is a potent mechanism explaining
      variation; it does not explain, however, the other two key features associated
      with personalities, consistency and correlations. Using the hawk-dove game and a
      frequency-dependent foraging game as examples, we here show that this changes
      fundamentally whenever one takes into account the physiological architecture
      underlying behavior (e.g., metabolism). We find that the inclusion of physiology
      changes the evolutionary predictions concerning consistency and correlations:
      while selection gives rise to inconsistent individuals and stochastically
      fluctuating behavioral correlations in scenarios that neglect physiology, we find
      high levels of behavioral consistency and tight and stable trait correlations in
      scenarios that incorporate physiology. The coevolution of behavioral and
      physiological traits also gives rise to adaptive physiological differences that
      are systematically associated with behavioral differences. As well as providing a
      framework for understanding behavioral consistency and behavioral correlations,
      our work thus also provides an explanation for systematic physiological
      differences within populations, a phenomenon that appears to exist in a wide
      range of species but that, up to now, has been poorly understood.

PMID- 22617260
TI  - Can life history predict the effect of demographic stochasticity on extinction
      risk?
AB  - Demographic stochasticity is important in determining extinction risks of small
      populations, but it is largely unknown how its effect depends on the life
      histories of species. We modeled effects of demographic stochasticity on
      extinction risk in a broad range of generalized life histories, using matrix
      models and branching processes. Extinction risks of life histories varied greatly
      in their sensitivity to demographic stochasticity. Comparing life histories,
      extinction risk generally increased with increasing fecundity and decreased with
      higher ages of maturation. Effects of adult survival depended on age of
      maturation. At lower ages of maturation, extinction risk peaked at intermediate
      levels of adult survival, but it increased along with adult survival at higher
      ages of maturation. These differences were largely explained by differences in
      sensitivities of population growth to perturbations of life-history traits.
      Juvenile survival rate contributed most to total demographic variance in the
      majority of life histories. Our general results confirmed earlier findings,
      suggesting that empirical patterns can be explained by a relatively simple model.
      Thus, basic life-history information can be used to assign life-history-specific
      sensitivity to demographic stochasticity. This is of great value when assessing
      the vulnerability of small populations.

PMID- 22617259
TI  - Population regulation and character displacement in a seasonal environment.
AB  - Competition has negative effects on population size and also drives ecological
      character displacement, that is, evolutionary divergence to utilize different
      portions of the resource spectrum. Many species undergo an annual cycle composed
      of a lean season of intense competition for resources and a breeding season. We
      use a quantitative genetic model to study the effects of differential
      reproductive output in the summer or breeding season on character displacement in
      the winter or nonbreeding season. The model is developed with reference to the
      avian family of Old World leaf warblers (Phylloscopidae), which breed in the
      temperate regions of Eurasia and winter in tropical and subtropical regions.
      Empirical evidence implicates strong winter density-dependent regulation driven
      by food shortage, but paradoxically, the relative abundance of each species
      appears to be determined by conditions in the summer. We show how population
      regulation in the two seasons becomes linked, with higher reproductive output by
      one species in the summer resulting in its evolution to occupy a larger portion
      of niche space in the winter. We find short-term ecological processes and longer
      term evolutionary processes to have comparable effects on a species population
      size. This modeling approach can also be applied to other differential effects of
      productivity across seasons.

PMID- 22617261
TI  - The nutrient-load hypothesis: patterns of resource limitation and community
      structure driven by competition for nutrients and light.
AB  - Resource competition theory predicts that the outcome of competition for two
      nutrients depends on the ratio at which these nutrients are supplied. Yet there
      is considerable debate whether nutrient ratios or absolute nutrient loads
      determine the species composition of phytoplankton and plant communities. Here we
      extend the classical resource competition model for two nutrients by including
      light as additional resource. Our results suggest the nutrient-load hypothesis,
      which predicts that nutrient ratios determine the species composition in
      oligotrophic environments, whereas nutrient loads are decisive in eutrophic
      environments. The underlying mechanism is that nutrient enrichment shifts the
      species interactions from competition for nutrients to competition for light,
      which favors the dominance of superior light competitors overshadowing all other
      species. Intermediate nutrient loads can generate high biodiversity through a
      fine-grained patchwork of two-species and three-species coexistence equilibria.
      Depending on the species traits, however, competition for nutrients and light may
      also produce multiple alternative stable states, suppressing the predictability
      of the species composition. The nutrient-load hypothesis offers a solution for
      several discrepancies between classical resource competition theory and field
      observations, explains why eutrophication often leads to diversity loss, and
      provides a simple conceptual framework for patterns of biodiversity and community
      structure observed in nature.

PMID- 22617262
TI  - Sex roles and mutual mate choice matter during mate sampling.
AB  - The roles of females and males in mating competition and mate choice have lately
      proven more variable, between and within species, than previously thought. In
      nature, mating competition occurs during mate search and is expected to be
      regulated by the numbers of potential mates and same-sex competitors. Here, we
      present the first study to test how a temporal change in sex roles affects mating
      competition and mate choice during mate sampling. Our model system (the marine
      fish Gobiusculus flavescens) is uniquely suitable because of its change in sex
      roles, from conventional to reversed, over the breeding season. As predicted from
      sex role theory, courtship was typically initiated by males and terminated by
      females early in the breeding season. The opposite pattern was observed late in
      the season, at which time several females often simultaneously courted the same
      male. Mate-searching females visited more males early than late in the breeding
      season. Our study shows that mutual mate choice and mating competition can have
      profound effects on female and male behavior. Future work needs to consider the
      dynamic nature of mating competition and mate choice if we aim to fully
      understand sexual selection in the wild.

PMID- 22617263
TI  - Body-size evolution on islands: are adult size variations in tiger snakes a
      nonadaptive consequence of selection on birth size?
AB  - Mean adult size has been used as the traditional measure of body size to explain
      trends of insular gigantism and dwarfism in a wide array of taxa. However,
      patterns of variation in body size at birth have received surprisingly little
      attention, leaving open the possibility that adult body-size differences are
      nonadaptive consequences of selection acting on neonate body size. Here I used an
      empirical and correlative approach to test this hypothesis in a mosaic of 12
      island and mainland snake populations in Australia. Data collected on 597 adult
      and 1,084 neonate tiger snakes showed that (1) both adult and neonate mean body
      sizes varied strongly across populations; (2) prey diversity and size
      convincingly explained birth-size variations: birth size-notably, gape size
      correlated with prey size; (3) neonate snout-vent length was significantly
      correlated with neonate gape size; and (4) neonate snout-vent length was
      significantly correlated with adult snout-vent length. Postnatal growth rates
      recorded under common-garden conditions differed across populations and were
      correlated with mean prey size. These data collectively suggest that (1) prey
      size is the main driver for the evolution of body size at birth in gape-limited
      predators, (2) adult size variations may reflect selective forces acting on
      earlier life stages, and (3) adult size variations may also reflect resource
      availability during ontogeny (notably, prey diversity).

PMID- 22617264
TI  - The direct and ecological costs of an ant-plant symbiosis.
AB  - How strong is selection for cheating in mutualisms? The answer depends on the
      type and magnitude of the costs of the mutualism. Here we investigated the direct
      and ecological costs of plant defense by ants in the association between Cordia
      nodosa, a myrmecophytic plant, and Allomerus octoarticulatus, a phytoecious ant.
      Cordia nodosa trees produce food and housing to reward ants that protect them
      against herbivores. For nearly 1 year, we manipulated the presence of A.
      octoarticulatus ants and most insect herbivores on C. nodosa in a full-factorial
      experiment. Ants increased plant growth when herbivores were present but
      decreased plant growth when herbivores were absent, indicating that hosting ants
      can be costly to plants. However, we did not detect a cost to ant colonies of
      defending host plants against herbivores. Although this asymmetry in costs
      suggests that the plants may be under stronger selection than the ants to cheat
      by withholding investment in their partner, the costs to C. nodosa are probably
      at least partly ecological, arising because ants tend scale insects on their host
      plants. We argue that ecological costs should favor resistance or traits other
      than cheating and thus that neither partner may face much temptation to cheat.

PMID- 22617265
TI  - Are there indirect fitness benefits of female extra-pair reproduction? Lifetime
      reproductive success of within-pair and extra-pair offspring.
AB  - The forces driving extra-pair reproduction by socially monogamous females, and
      the resulting genetic polyandry, remain unclear. A testable prediction of the
      hypothesis that extra-pair reproduction partly reflects indirect selection on
      females is that extra-pair young (EPY) will be fitter than their within-pair
      young (WPY) maternal half-siblings. This prediction has not been comprehensively
      tested in a wild population, requiring data on the lifetime reproductive success
      (LRS) of maternal half-sib EPY and WPY. We used 17 years of genetic parentage
      data from song sparrows, Melospiza melodia, to compare the LRS of hatched EPY and
      WPY maternal half-siblings measured as their lifetime number of hatched
      offspring, recruited offspring, and hatched grandoffspring. EPY hatchlings were
      not significantly fitter than WPY hatchlings for any of three measures of LRS.
      Furthermore, opposite to prediction, EPY hatchlings tended to have lower LRS than
      their maternal half-sibling WPY hatchlings on average. EPY also tended to be less
      likely to survive to hatch than their maternal half-sibling WPY. Taken together,
      these results fail to support one key hypothesis explaining the evolution of
      genetic polyandry by socially monogamous females and suggest there may be weak
      indirect selection against female extra-pair reproduction in song sparrows.

PMID- 22617266
TI  - Biophysical modeling of the temporal niche: from first principles to the
      evolution of activity patterns.
AB  - Most mammals can be characterized as nocturnal or diurnal. However infrequently,
      species may overcome evolutionary constraints and alter their activity patterns.
      We modeled the fundamental temporal niche of a diurnal desert rodent, the golden
      spiny mouse, Acomys russatus. This species can shift into nocturnal activity in
      the absence of its congener, the common spiny mouse, Acomys cahirinus, suggesting
      that it was competitively driven into diurnality and that this shift in a small
      desert rodent may involve physiological costs. Therefore, we compared metabolic
      costs of diurnal versus nocturnal activity using a biophysical model to evaluate
      the preferred temporal niche of this species. The model predicted that energy
      expenditure during foraging is almost always lower during the day except during
      midday in summer at the less sheltered microhabitat. We also found that a shift
      in summer to foraging in less sheltered microhabitats in response to predation
      pressure and food availability involves a significant physiological cost
      moderated by midday reduction in activity. Thus, adaptation to diurnality may
      reflect the "ghost of competition past"; climate-driven diurnality is an
      alternative but less likely hypothesis. While climate is considered to play a
      major role in the physiology and evolution of mammals, this is the first study to
      model its potential to affect the evolution of activity patterns of mammals.

PMID- 22617267
TI  - Use of an exotic host plant affects mate choice in an insect herbivore.
AB  - The colonization of exotic plants by herbivorous insects has provided
      opportunities for investigating causes and consequences of the evolution of niche
      breadth. The butterfly Lycaeides melissa utilizes exotic alfalfa, Medicago
      sativa, which is a relatively poor larval resource, and previous studies have
      found that caterpillars that consume M. sativa develop into smaller and less
      fecund adults. Here we investigate the effect of smaller female body size on male
      mate preference, a previously unexplored consequence of novel host use. Smaller
      females, which developed on the exotic host, were less likely to be visited by
      males. This result was confirmed with a second set of choice tests involving
      females reared on a single plant species, thus ruling out host-specific
      confounding factors. We suggest that an effect on mate choice be considered part
      of the complex suite of factors determining persistence of herbivorous insects
      following colonization of new habitats or resources.

PMID- 22617268
TI  - Parasitized mates increase infection risk for partners.
AB  - Individuals can gain fitness benefits and costs through their mates. However,
      studies on sexual selection have tended to focus on genetic benefits. A
      potentially widespread cost of pairing with a parasitized mate is that doing so
      will increase an individual's parasite abundance. Such a cost has been overlooked
      in systems in which parasites are indirectly transmitted. We manipulated the
      abundance of the nematode parasite Trichostrongylus tenuis, an indirectly
      transmitted parasite, within pairs of wild red grouse Lagopus lagopus scoticus in
      spring. Parasite levels were correlated within pairs before the experiment. We
      removed parasites from males, females, or both members of the pair and evaluated
      individual parasite uptake over the subsequent breeding period. At the end of the
      breeding season, an individual's parasite abundance was greater when its mate had
      not been initially purged of parasites. This cost appeared to be greater for
      males. We discuss the implications of our results in relation to the costs that
      parasites may have on sexual selection processes.

PMID- 22617269
TI  - Latitudinal patterns in rodent metabolic flexibility.
AB  - Macrophysiology is defined as the study of variation in physiological traits
      including physiological trait flexibility-over large geographical and temporal
      scales, and the ecological implications of this variation. A classic example of a
      macrophysiological trend is the one emerging from the climatic variability
      hypothesis, which states that as the range of climatic fluctuation experienced by
      terrestrial animals increases with latitude, individuals at higher latitudes
      should be more plastic than individuals inhabiting lower latitudes. In this
      context, we evaluate the correlation between absolute metabolic scope during cold
      exposure (an instantaneous measure of metabolic flexibility) and different
      geographic and climatic variables for 48 rodent species. Conventional and
      phylogenetic informed analyses indicated a positive correlation between metabolic
      scope and geographic latitude. These findings, together with previous reports on
      latitudinal pattern in phenotypic flexibility, suggest that an increase in
      physiological flexibility with latitude may hold for many phenotypic traits.

PMID- 22617270
TI  - When is general wariness favored in avoiding multiple predator types?
AB  - Adaptive responses to predation are generally studied assuming only one predator
      type exists, but most prey species are depredated by multiple types. When
      multiple types occur, the optimal antipredator response level may be determined
      solely by the probability of attack by the relevant predator: "specific
      responsiveness." Conversely, an increase in the probability of attack by one
      predator type might increase responsiveness to an alternative predator type:
      "general wariness." We formulate a mathematical model in which a prey animal
      perceives a cue providing information on the probability of two predator types
      being present. It can perform one of two evasive behaviors that vary in their
      suitability as a response to the "wrong" predator type. We show that general
      wariness is optimal when incorrect behavioral decisions have differential fitness
      costs. Counterintuitively, difficulty in discriminating between predator types
      does not favor general wariness. We predict that where responses to predator
      types are mutually exclusive (e.g., referential alarm-calling), specific
      responsiveness will occur; we suggest that prey generalize their defensive
      responses based on cue similarity due to an assumption of response utility; and
      we predict, with relevance to conservation, that habituation to human disturbance
      should generalize only to predators that elicit the same antipredator response as
      humans.

PMID- 22617271
TI  - The offspring-development-time/offspring-number trade-off.
AB  - The metabolic theory of ecology (MTE) states that metabolic rate, ruled mainly by
      individual mass and temperature, determines many other biological rates. This
      view of ecology as ruled by the laws of physics and thermodynamics contrasts with
      life-history-optimization (LHO) theories, where traits are shaped by evolutionary
      processes. Integrating the MTE and LHO can lead, however, to a synthetic theory
      of ecology. In this work, we link the two theories to show that offspring
      development time is the result of both maternal investment in offspring and the
      metabolic constraints on offspring growth. We formulate a model that captures how
      offspring development time is the consequence of both offspring growth rate,
      determined by temperature and allometric scaling in accordance with the MTE, and
      the size reached by offspring at the end of the developmental period, determined
      mainly by LHO and reproductive strategies. We first extend the trade-off between
      offspring size and offspring number to ectotherms, showing that increased body
      temperatures result in increased resources available for reproduction. We then
      combine this trade-off with the general ontogenetic growth model to show that
      there is a trade-off between the number of offspring produced and offspring
      development time. The model predicts a shorter developmental time in organisms
      producing larger numbers of offspring.

PMID- 22617273
TI  - Errors in a paper on the Millennium Villages project.

PMID- 22617274
TI  - Acute kidney injury.
AB  - Acute kidney injury (formerly known as acute renal failure) is a syndrome
      characterised by the rapid loss of the kidney's excretory function and is
      typically diagnosed by the accumulation of end products of nitrogen metabolism
      (urea and creatinine) or decreased urine output, or both. It is the clinical
      manifestation of several disorders that affect the kidney acutely. Acute kidney
      injury is common in hospital patients and very common in critically ill patients.
      In these patients, it is most often secondary to extrarenal events. How such
      events cause acute kidney injury is controversial. No specific therapies have
      emerged that can attenuate acute kidney injury or expedite recovery; thus,
      treatment is supportive. New diagnostic techniques (eg, renal biomarkers) might
      help with early diagnosis. Patients are given renal replacement therapy if acute
      kidney injury is severe and biochemical or volume-related, or if uraemic-toxaemia
      related complications are of concern. If patients survive their illness and do
      not have premorbid chronic kidney disease, they typically recover to dialysis
      independence. However, evidence suggests that patients who have had acute kidney
      injury are at increased risk of subsequent chronic kidney disease.

PMID- 22617275
TI  - Residential care facilities: a key sector in the spectrum of long-term care
      providers in the United States.
AB  - RCFs in the United States totaled 31,100 in 2010, with 971,900 state-licensed,
      certified, or registered residential care beds. About one-half of RCFs were small
      facilities which served one-tenth of all RCF residents. The remaining RCFs were
      medium-sized facilities (16%) which served about one-tenth of all RCF residents,
      large facilities (28%) which served about one-half of all RCF residents, and
      extra large facilities (7%) which housed about three-tenths of all RCF residents.
      RCFs were predominantly for profit (82%), not part of a chain (62%), and located
      in an MSA (81%). Small RCFs were more likely to be for profit than larger RCFs.
      The proportion of chain-affiliated RCFs grew with increasing facility size. Small
      and extra large RCFs were most likely to be located in an MSA, while medium RCFs
      were least likely to be in an MSA. RCFs were most commonly located in the West.
      The mix of facility sizes varied by region. The West had almost twice as many
      residential care beds per 1,000 persons aged 85 and over as the Northeast (245 to
      131). Comparing the supply of RCF beds with nursing home beds (data compiled by
      Centers for Medicare & Medicaid Services) shows that the supply of RCF beds (245)
      and nursing home beds (203) per 1,000 persons aged 85 and over was relatively
      comparable in the West, but nursing home beds far outnumbered RCF beds in all
      other regions. There were about twice as many nursing home beds as RCF beds per
      1,000 persons aged 85 and over in the South (325 to 164), Midwest (390 to 177),
      and Northeast (303 to 131). More research is needed to identify and examine
      factors that may explain these regional differences in both the supply of
      residential care beds, including variations in state regulation and financing of
      different types of LTC providers, and in consumer preferences for different kinds
      of long-term services and support. RCFs serve primarily a private-pay adult
      population (6). However, the use of Medicaid financing for services in
      residential care settings has gradually increased in recent years (7). About 4
      out of 10 RCFs had at least one resident who had some or all of their LTC
      services paid by Medicaid. The percentage of facilities having residents who
      received LTC services paid by Medicaid varied by facility size. Although nearly
      all RCFs provided basic health monitoring (96%) and incontinence care (93%),
      larger RCFs were more likely than smaller RCFs to offer occupational and physical
      therapy. Larger RCFs were also more likely than small RCFs to provide social
      services counseling and case management. The provision of skilled nursing
      services did not vary by facility size. This report presents national estimates
      of RCFs using data from the first-ever national probability sample survey of RCFs
      with four or more beds. Findings on differences in selected characteristics and
      services offered by facility size and on regional variations in the supply of
      beds provide useful information to policymakers, LTC providers, and consumer
      advocates as they plan to meet the needs of an aging population. Moreover, these
      findings establish baseline national estimates as researchers continue to track
      growth and changes in the residential care industry.

PMID- 22617276
TI  - Current models of the mode of action of Bacillus thuringiensis insecticidal
      crystal proteins: a critical review.
AB  - Bacillus thuringiensis (Bt) Cry toxins constitute the active ingredient in the
      most widely used biological insecticides and insect-resistant transgenic crops. A
      clear understanding of their mode of action is necessary for improving these
      products and ensuring their continued use. Accordingly, a long history of
      intensive research has established that their toxic effect is due primarily to
      their ability to form pores in the plasma membrane of the midgut epithelial cells
      of susceptible insects. In recent years, a rather elaborate model involving the
      sequential binding of the toxins to different membrane receptors has been
      developed to describe the events leading to membrane insertion and pore
      formation. However, it was also proposed recently that, in contradiction with
      this mechanism, Bt toxins function by activating certain intracellular signaling
      pathways which lead to the necrotic death of their target cells without the need
      for pore formation. Because work in this field has largely focused, for several
      years, on the elaboration and promotion of these two models, the present revue
      examines in detail the experimental evidence on which they are based. It is
      concluded that the presently available information still supports the notion that
      Bt Cry toxins act by forming pores, but most events leading to their formation,
      following binding of the activated toxins to their receptors, remain relatively
      poorly understood.

PMID- 22617277
TI  - Dietary fibre intake and ischaemic heart disease mortality: the European
      Prospective Investigation into Cancer and Nutrition-Heart study.
AB  - BACKGROUND/OBJECTIVES: Evidence from prospective studies is consistent in showing
      an inverse association between dietary fibre intake and risk of ischaemic heart
      disease (IHD), but whether dietary fibre from various food sources differ in
      their effect on IHD risk is less clear. The objective of this study was to assess
      the associations of total and food sources of dietary fibre with IHD mortality in
      the European Prospective Investigation into Cancer and Nutrition-Heart study.
      SUBJECTS/METHODS: Participants were 306,331 men and women from eight European
      countries. Dietary fibre intake was assessed using centre or country-specific
      diet questionnaires and calibrated using a 24-h diet recall. RESULTS: After an
      average follow-up of 11.5 years, there were 2381 IHD deaths among participants
      without cardiovascular disease at baseline. The calibrated intake of dietary
      fibre was inversely related with IHD mortality; each 10 g/day was associated with
      a 15% lower risk (relative risk (RR) 0.85; 95% confidence interval (CI): 0.73
      0.99, P=0.031). There was no difference in the associations of the individual
      food sources of dietary fibre with the risk of IHD mortality; RR for each 5 g/day
      higher cereal fibre intake was 0.91 (CI: 0.82-1.01), RR for each 2.5 g/day fruit
      fibre intake was 0.94 (CI: 0.88-1.01) and RR for each 2.5 g/day vegetable fibre
      intake was 0.90 (95% CI: 0.76-1.07). CONCLUSION: A higher consumption of dietary
      fibre is associated with a lower risk of fatal IHD with no clear difference in
      the association with IHD for fibre from cereals, fruits or vegetables.

PMID- 22617278
TI  - Preoperative immunonutrition in patients at nutritional risk: results of a double
      blinded randomized clinical trial.
AB  - BACKGROUND/OBJECTIVES: To evaluate the impact of preoperative immunonutrition
      (IN) on postoperative morbidity in patients at risk of malnutrition undergoing
      major gastrointestinal (GI) surgery. SUBJECTS/METHODS: The combination of
      malnutrition and major GI surgery entails high morbidity. The Nutritional Risk
      Score (NRS) reliably identifies patients who need preoperative nutrition; the
      optimal nutritional formula for these patients still needs to be defined. In all,
      152 patients with a NRS>=3 and undergoing elective major GI surgery were
      randomized between IN or isocaloric-isonitrogenous nutrition (ICN) given for 5
      days preoperatively. Patients and caregivers were blinded for the allocated
      intervention. Thirty days complication rate was the primary endpoint. Infections,
      length of hospital stay and compliance were considered as secondary outcomes.
      RESULTS: Overall, 145 patients were available for analysis; the 73 patients in
      the IN group matched well with the 72 ICN patients with regards to patient's and
      surgical characteristics. In all, 39 IN and 33 ICN patients experienced a total
      of 48 and 50 postoperative complications, respectively (P=0.723). Both groups did
      not differ significantly concerning infectious (13 vs 9) complications.
      Independent risk factors for overall complications were malignant disease (odds
      ratio (OR)=4.304; confidence interval (CI) 1.317-14.002) and operative time
      (OR=1.004; CI 1.000-1.008). CONCLUSION: In patients at nutritional risk,
      complications, infections and hospital stay after major GI surgery were
      comparable regardless of preoperative supplementation with IN or ICN.

PMID- 22617279
TI  - Effects of long-term intake of lactotripeptides on cardiovascular risk factors in
      hypertensive subjects.
AB  - BACKGROUND/OBJECTIVES: Lactobacillus helveticus LBK-16H-fermented milk products
      containing tripeptides isoleucine-proline-proline and valine-proline-proline
      lower blood pressure in hypertensive subjects using office and home blood
      pressure registration. The present study was aimed to evaluate the effects of two
      doses of these lactotripeptides on 24-h ambulatory blood pressure and lipidomics
      profiles in mildly hypertensive subjects. SUBJECTS/METHODS: In a randomized,
      double-blind, placebo-controlled parallel group study, 89 mildly hypertensive
      subjects ingested, after a 1-month run-in period, a fermented milk drink with 5
      mg per day of lactotripeptides during 3 months, and a milk drink with 50 mg per
      day of lactotripeptides for the following 3 months, or a placebo milk drink
      without lactotripeptides. Ambulatory blood pressure (24 h) was recorded at
      baseline and at the end of the intervention periods. Lipidomics profiles were
      characterized before and after the 6-month intervention. RESULTS: After the
      second intervention period (50 mg per day of lactotripeptides), systolic and
      diastolic 24-h blood pressures decreased significantly in the peptide, but not in
      the placebo group. However, the treatment effects -2.6 mm Hg (95% confidence
      interval (CI): -5.7 to 0.4) in systolic and -1.3 mm Hg (95% CI: -3.4 to 0.8) in
      diastolic blood pressure did not reach statistic significance. Ingestion of 5 mg
      per day of lactotripeptides for 3 months did not lower blood pressure. The
      peptide group was dominated by decrease in multiple phospholipids (PL).
      CONCLUSIONS: Ingestion of fermented milk with daily dose of 50 mg of
      lactotripeptides appears to lower elevated blood pressure slightly from the
      baseline, but not significantly compared with the placebo group and to induce
      significant decreases in multiple PL.

PMID- 22617280
TI  - Symptom structure of antipsychotic-induced obsessive compulsive symptoms in
      schizophrenia patients.
AB  - OBJECTIVE: The use of clozapine or other second generation antipsychotics (SGAs)
      has been reported to produce obsessive compulsive (OC) symptoms as adverse mental
      affects. However, it is not yet clear if SGA-induced OC symptoms have the same
      phenomenological characteristics as those displayed in obsessive compulsive
      disorder (OCD). This study investigated the nature of symptoms and dimensions of
      SGA-induced OC symptoms in schizophrenia patients, which were then compared with
      those reported in pure OCD. METHODS: The study subjects were fifty-one
      schizophrenia patients with SGA-induced OC symptoms. Symptom evaluation was
      performed using the Korean version of the Yale-Brown Obsessive Compulsive Scale
      (Y-BOCS). Exploratory factor analysis of symptom categories of Y-BOCS symptom
      checklist (Y-BOCS-SC) was conducted. RESULTS: Frequencies of individual symptom
      categories were comparable to those reported in Korean OCD patients. Five factors
      (forbidden thoughts, hoarding, cleaning, symmetry, and counting) were generated
      from 13 main symptom categories, which accounted for 70.7% of the total variance.
      This factor structure is also remarkably similar to those reported in pure OCD
      patients. The factor score of 'cleaning' was significantly correlated with the
      overall severity of OC symptoms (P<0.01). CONCLUSION: A high level of similarity
      between the nature of symptoms and dimensions identified in patients with SGA
      induced OC symptoms and those revealed in OCD patients suggests a common
      biological mechanism underlying these two clinical conditions.

PMID- 22617285
TI  - Spin-motive force due to a gyrating magnetic vortex.
AB  - A change of magnetic flux through a circuit induces an electromotive force. By
      analogy, a recently predicted force that results from the motion of non-uniform
      spin structures has been termed the spin-motive force. Although recent
      experiments seem to confirm its presence, a direct signature of the spin-motive
      force has remained elusive. Here we report the observation of a real-time spin
      motive force produced by the gyration of a magnetic vortex core. We find a good
      agreement between the experimental results, theory and micromagnetic simulations,
      which taken as a whole provide strong evidence in favour of a spin-motive force.

PMID- 22617286
TI  - All optical reconfiguration of optomechanical filters.
AB  - Reconfigurable optical filters are of great importance for applications in
      optical communication and information processing. Of particular interest are
      tuning techniques that take advantage of mechanical deformation of the devices,
      as they offer wider tuning range. Here we demonstrate reconfiguration of coupled
      photonic crystal nanobeam cavities by using optical gradient force induced
      mechanical actuation. Propagating waveguide modes that exist over a wide
      wavelength range are used to actuate the structures and control the resonance of
      localized cavity modes. Using this all-optical approach, more than 18 linewidths
      of tuning range is demonstrated. Using an on-chip temperature self-referencing
      method, we determine that 20% of the total tuning was due to optomechanical
      reconfiguration and the rest due to thermo-optic effects. By operating the device
      at frequencies higher than the thermal cutoff, we show high-speed operation
      dominated by just optomechanical effects. Independent control of mechanical and
      optical resonances of our structures is also demonstrated.

PMID- 22617287
TI  - Electric-field control of domain wall motion in perpendicularly magnetized
      materials.
AB  - Domain wall motion in materials exhibiting perpendicular magnetic anisotropy has
      been the subject of intensive research because of its large potential for future
      spintronic devices. Recently, it has been shown that perpendicular anisotropy of
      thin films can be influenced by electric fields. Voltage-controlled magnetic
      switching has already been realized, which is envisioned to lead to low-power
      logic and memory devices. Here we demonstrate a radically new application of this
      effect, namely control of domain wall motion by electric fields. We show that an
      applied voltage perpendicular to a Co or CoB wire can significantly increase or
      decrease domain wall velocities. Velocity modification over an order of magnitude
      is demonstrated (from 0.4 to 4 MUm s(-1)), providing a first step towards
      electrical control of domain wall devices. This opens up possibilities of real
      time and local control of domain wall motion by electric fields at extremely low
      power cost.

PMID- 22617288
TI  - Evolution of a tissue-specific silencer underlies divergence in the expression of
      pax2 and pax8 paralogues.
AB  - Recent studies underscore a role for the differential degeneration of enhancers
      in the evolutionary diversification of paralogue expression. However, no one has
      reported evidence for the involvement of innovative cis-regulatory changes. Here
      we show that silencer innovation diversified expression of the vertebrate
      paralogues, pax2 and pax8. pax2 shows multi-tissue expression, as does the
      ancestral amphioxus orthologue, pax2/5/8, whereas pax8 expression localizes to a
      subset of pax2-expressing tissues. We reveal that both pax2 and pax8 retain
      ancestral enhancers capable of directing pax2-like, multi-tissue expression.
      However, a silencer within the pax8 proximal promoter suppresses pleiotropic
      enhancer activity outside the pax8-expressing tissues. In contrast, the
      combination of the pax2 proximal promoter with either the pax8 or pax2 enhancer
      recapitulates pax2-like expression, as in the amphioxus pax2/5/8 promoter. We
      propose that silencer innovation, rather than enhancer degeneration, was crucial
      for the divergent expression of paralogues with pleiotropic enhancers inherited
      from their common progenitor.

PMID- 22617289
TI  - Targeted suppression of claudin-5 decreases cerebral oedema and improves
      cognitive outcome following traumatic brain injury.
AB  - Traumatic brain injury is the leading cause of death in children and young adults
      globally. Malignant cerebral oedema has a major role in the pathophysiology that
      evolves after severe traumatic brain injury. Added to this is the significant
      morbidity and mortality from cerebral oedema associated with acute stroke,
      hypoxic ischemic coma, neurological cancers and brain infection. Therapeutic
      strategies to prevent cerebral oedema are limited and, if brain swelling
      persists, the risks of permanent brain damage or mortality are greatly
      exacerbated. Here we show that a temporary and size-selective modulation of the
      blood-brain barrier allows enhanced movement of water from the brain to the blood
      and significantly impacts on brain swelling. We also show cognitive improvement
      in mice with focal cerebral oedema following administration in these animals of
      short interfering RNA directed against claudin-5. These observations may have
      profound consequences for early intervention in cases of traumatic brain injury,
      or indeed any neurological condition where cerebral oedema is the hallmark
      pathology.

PMID- 22617290
TI  - An atlas of DNA methylomes in porcine adipose and muscle tissues.
AB  - It is evident that epigenetic factors, especially DNA methylation, have essential
      roles in obesity development. Here, using pig as a model, we investigate the
      systematic association between DNA methylation and obesity. We sample eight
      variant adipose and two distinct skeletal muscle tissues from three pig breeds
      living within comparable environments but displaying distinct fat level. We
      generate 1,381 Gb of sequence data from 180 methylated DNA immunoprecipitation
      libraries, and provide a genome-wide DNA methylation map as well as a gene
      expression map for adipose and muscle studies. The analysis shows global
      similarity and difference among breeds, sexes and anatomic locations, and
      identifies the differentially methylated regions. The differentially methylated
      regions in promoters are highly associated with obesity development via
      expression repression of both known obesity-related genes and novel genes. This
      comprehensive map provides a solid basis for exploring epigenetic mechanisms of
      adipose deposition and muscle growth.

PMID- 22617292
TI  - Microtubule and cortical forces determine platelet size during vascular platelet
      production.
AB  - Megakaryocytes release large preplatelet intermediates into the sinusoidal blood
      vessels. Preplatelets convert into barbell-shaped proplatelets in vitro to
      undergo repeated abscissions that yield circulating platelets. These observations
      predict the presence of circular-preplatelets and barbell-proplatelets in blood,
      and two fundamental questions in platelet biology are what are the forces that
      determine barbell-proplatelet formation, and how is the final platelet size
      established. Here we provide insights into the terminal mechanisms of platelet
      production. We quantify circular-preplatelets and barbell-proplatelets in human
      blood in high-resolution fluorescence images, using a laser scanning cytometry
      assay. We demonstrate that force constraints resulting from cortical microtubule
      band diameter and thickness determine barbell-proplatelet formation. Finally, we
      provide a mathematical model for the preplatelet to barbell conversion. We
      conclude that platelet size is limited by microtubule bundling, elastic bending,
      and actin-myosin-spectrin cortex forces.

PMID- 22617291
TI  - Gene-associated markers provide tools for tackling illegal fishing and false eco
      certification.
AB  - Illegal, Unreported and Unregulated fishing has had a major role in the
      overexploitation of global fish populations. In response, international
      regulations have been imposed and many fisheries have been 'eco-certified' by
      consumer organizations, but methods for independent control of catch certificates
      and eco-labels are urgently needed. Here we show that, by using gene-associated
      single nucleotide polymorphisms, individual marine fish can be assigned back to
      population of origin with unprecedented high levels of precision. By applying
      high differentiation single nucleotide polymorphism assays, in four commercial
      marine fish, on a pan-European scale, we find 93-100% of individuals could be
      correctly assigned to origin in policy-driven case studies. We show how case
      targeted single nucleotide polymorphism assays can be created and forensically
      validated, using a centrally maintained and publicly available database. Our
      results demonstrate how application of gene-associated markers will likely
      revolutionize origin assignment and become highly valuable tools for fighting
      illegal fishing and mislabelling worldwide.

PMID- 22617293
TI  - Fasciola hepatica is associated with the failure to detect bovine tuberculosis in
      dairy cattle.
AB  - Bovine tuberculosis (BTB) is a significant and intractable disease of cattle
      caused by Mycobacterium bovis. In the United Kingdom, despite an aggressive
      eradication programme, the prevalence of BTB is increasing with an unexplained,
      exponential rise in cases year on year. Here we show in a study involving 3,026
      dairy herds in England and Wales that there is a significant negative association
      between exposure to the common, ubiquitous helminth parasite, Fasciola hepatica
      and diagnosis of BTB. The magnitude of the single intradermal comparative
      cervical tuberculin test used to diagnose BTB is reduced in cattle experimentally
      co-infected with M. bovis and F. hepatica. We estimate an under-ascertainment
      rate of about one-third (95% confidence interval 27-38%) among our study farms,
      in the hypothetical situation of no exposure to F. hepatica. This finding may in
      part explain the continuing spread of BTB and the failure of the current
      eradication programme in the United Kingdom.

PMID- 22617294
TI  - Recombinant SINEs are formed at high frequency during induced retrotransposition
      in vivo.
AB  - Non-long terminal repeat Retrotransposons are referred to as long interspersed
      nuclear elements (LINEs) and their non-autonomous partners are short interspersed
      nuclear elements (SINEs). It is believed that an active SINE copy, upon
      retrotransposition, generates near identical copies of itself, which subsequently
      accumulate mutations resulting in sequence polymorphism. Here we show that when a
      retrotransposition-competent cell line of the parasitic protist Entamoeba
      histolytica, transfected with a marked SINE copy, is induced to retrotranspose,
      >20% of the newly retrotransposed copies are neither identical to the marked SINE
      nor to the mobilized resident SINEs. Rather they are recombinants of resident
      SINEs and the marked SINE. They are a consequence of retrotransposition and not
      DNA recombination, as they are absent in cells not expressing the
      retrotransposition functions. This high-frequency recombination provides a new
      explanation for the existence of mosaic SINEs, which may impact on genetic
      analysis of SINE lineages, and measurement of phylogenetic distances.

PMID- 22617295
TI  - Closed network growth of fullerenes.
AB  - Tremendous advances in nanoscience have been made since the discovery of the
      fullerenes; however, the formation of these carbon-caged nanomaterials still
      remains a mystery. Here we reveal that fullerenes self-assemble through a closed
      network growth mechanism by incorporation of atomic carbon and C(2). The growth
      processes have been elucidated through experiments that probe direct growth of
      fullerenes upon exposure to carbon vapour, analysed by state-of-the-art Fourier
      transform ion cyclotron resonance mass spectrometry. Our results shed new light
      on the fundamental processes that govern self-assembly of carbon networks, and
      the processes that we reveal in this study of fullerene growth are likely be
      involved in the formation of other carbon nanostructures from carbon vapour, such
      as nanotubes and graphene. Further, the results should be of importance for
      illuminating astrophysical processes near carbon stars or supernovae that result
      in C(60) formation throughout the Universe.

PMID- 22617296
TI  - Superionic glass-ceramic electrolytes for room-temperature rechargeable sodium
      batteries.
AB  - Innovative rechargeable batteries that can effectively store renewable energy,
      such as solar and wind power, urgently need to be developed to reduce greenhouse
      gas emissions. All-solid-state batteries with inorganic solid electrolytes and
      electrodes are promising power sources for a wide range of applications because
      of their safety, long-cycle lives and versatile geometries. Rechargeable sodium
      batteries are more suitable than lithium-ion batteries, because they use abundant
      and ubiquitous sodium sources. Solid electrolytes are critical for realizing all
      solid-state sodium batteries. Here we show that stabilization of a high
      temperature phase by crystallization from the glassy state dramatically enhances
      the Na(+) ion conductivity. An ambient temperature conductivity of over 10(-4) S
      cm(-1) was obtained in a glass-ceramic electrolyte, in which a cubic Na(3)PS(4)
      crystal with superionic conductivity was first realized. All-solid-state sodium
      batteries, with a powder-compressed Na(3)PS(4) electrolyte, functioned as a
      rechargeable battery at room temperature.

PMID- 22617297
TI  - Unreachable glass transition in dilute dipolar magnet.
AB  - In magnetic systems the combined effects of disorder and frustration may cause
      the moments to freeze into a disordered state at a spin-glass transition. Recent
      experiments have shown that the rare earth compound LiHo(0.045)Y(0.955)F(4)
      freezes, but that the transition is unreachable because of dynamics that are
      10(7) times slower than in ordinary spin-glass materials. This conclusion refutes
      earlier investigations reporting a speed-up of the dynamics into an exotic anti
      glass phase caused by entanglement of quantum dipoles. Here we present a theory,
      backed by numerical simulations, which describes the material in terms of
      classical dipoles governed by Glauber dynamics. The dipoles freeze and we find
      that the ultra-slow dynamics are caused by rare, strongly ordered clusters, which
      give rise to a previously predicted, but hitherto unobserved, Griffths phase
      between the paramagnetic and spin-glass phases. In addition, the hyperfine
      interaction creates a high energy barrier to flipping the electronic spin,
      resulting in a clear signature in the dynamic correlation function.

PMID- 22617298
TI  - Suppression of spin-bath dynamics for improved coherence of multi-spin-qubit
      systems.
AB  - Multi-qubit systems are crucial for the advancement and application of quantum
      science. Such systems require maintaining long coherence times while increasing
      the number of qubits available for coherent manipulation. For solid-state spin
      systems, qubit coherence is closely related to fundamental questions of many-body
      spin dynamics. Here we apply a coherent spectroscopic technique to characterize
      the dynamics of the composite solid-state spin environment of nitrogen-vacancy
      colour centres in room temperature diamond. We identify a possible new mechanism
      in diamond for suppression of electronic spin-bath dynamics in the presence of a
      nuclear spin bath of sufficient concentration. This suppression enhances the
      efficacy of dynamical decoupling techniques, resulting in increased coherence
      times for multi-spin-qubit systems, thus paving the way for applications in
      quantum information, sensing and metrology.

PMID- 22617299
TI  - Osteoporosis or low bone mass at the femur neck or lumbar spine in older adults:
      United States, 2005-2008.
AB  - Nine percent of adults over age 50 years had osteoporosis at either the femur
      neck or lumbar spine and roughly one-half had low bone mass at either of these
      two skeletal sites. Having osteoporosis raises the risk of experiencing fractures
      (1,2). The prevalence of osteoporosis or low bone mass at either the femur neck
      or lumbar spine was not the same as the prevalence of these conditions when the
      two skeletal sites were considered separately because some individuals had these
      conditions at one of the skeletal sites but not the other. The prevalence of
      osteoporosis or low bone mass differed by age, sex, and race and ethnicity. The
      prevalence was higher in women and increased with age. Differences by race and
      ethnicity varied depending on sex and skeletal status category, but when compared
      with non-Hispanic white persons, Mexican-American persons, and persons of other
      races tended to be at higher risk, and non-Hispanic black persons tended to be at
      lower risk of either osteoporosis or low bone mass at the femur neck or lumbar
      spine.

PMID- 22617300
TI  - Autonomous spacecraft landing through human pre-attentive vision.
AB  - In this work, we exploit a computational model of human pre-attentive vision to
      guide the descent of a spacecraft on extraterrestrial bodies. Providing the
      spacecraft with high degrees of autonomy is a challenge for future space
      missions. Up to present, major effort in this research field has been
      concentrated in hazard avoidance algorithms and landmark detection, often by
      reference to a priori maps, ranked by scientists according to specific scientific
      criteria. Here, we present a bio-inspired approach based on the human ability to
      quickly select intrinsically salient targets in the visual scene; this ability is
      fundamental for fast decision-making processes in unpredictable and unknown
      circumstances. The proposed system integrates a simple model of the spacecraft
      and optimality principles which guarantee minimum fuel consumption during the
      landing procedure; detected salient sites are used for retargeting the spacecraft
      trajectory, under safety and reachability conditions. We compare the decisions
      taken by the proposed algorithm with that of a number of human subjects tested
      under the same conditions. Our results show how the developed algorithm is
      indistinguishable from the human subjects with respect to areas, occurrence and
      timing of the retargeting.

PMID- 22617301
TI  - Serum interleukin-6 as a prognostic biomarker in patients with metastatic
      melanoma.
AB  - Interleukin-6 (IL-6) is an immunomodulatory cytokine produced by both normal
      cells and tumor cells, including melanoma cells. The specific biological function
      of IL-6 in melanoma is unknown. The present study examined whether the serum
      concentration of IL-6 can predict prognosis in patients with metastatic melanoma.
      IL-6 was measured by ELISA in serum samples from 103 patients with metastatic
      melanoma obtained before IL-2-based immunotherapy. Patients with metastatic
      melanoma had higher serum IL-6 than healthy individuals (median 3.4 ng/l, range
      0.3-93 ng/l vs. median 1.4 ng/l, range 0.25-22.5 ng/l, P<0.0001). Pretreatment
      serum IL-6 was elevated in 43% of the patients. Patients with elevated
      pretreatment serum IL-6 had shorter overall survival (OS) compared with patients
      with normal serum IL-6 (P<0.0002). The median OS was 10.8 months [95% confidence
      interval (CI): 8.86-13.46] in patients with normal serum IL-6 compared with 4.5
      months (95% CI: 3.04-7.39) in patients with elevated serum IL-6. Multivariate Cox
      analysis showed that serum IL-6 [hazard ratio (HR)=1.82, 95% CI: 1.19-2.78,
      P=0.006] and serum lactate dehydrogenase (HR=2.02, 95% CI: 1.31-3.11, P=0.001)
      were independent prognostic biomarkers of OS. A combination variable of elevated
      serum IL-6 and elevated serum lactate dehydrogenase almost quadrupled the risk of
      early death (HR=3.67, 95% CI: 2.17-6.20, P<0.0001) compared with patients with
      normal serum levels of these two biomarkers. Elevated serum IL-6 is an
      independent prognostic biomarker of short OS in patients with metastatic
      melanoma. A larger retrospective study is ongoing to confirm the findings. To
      validate serum IL-6 further as a prognostic biomarker, a prospective study is
      required.

PMID- 22617302
TI  - Laparoscopic nephrectomy: looking back, moving forward.
AB  - This manuscript reviews the history of laparoscopic nephrectomy and addresses the
      future trends of this minimally invasive operation.

PMID- 22617303
TI  - Surgeon controlled robot-assisted laparoscopic radical cystectomy: current review
      of oncologic and functional outcomes.
AB  - Surgeon controlled robot-assisted laparoscopic radical cystectomy (RARC) is
      becoming a viable treatment option for patients with muscle-invasive bladder
      cancer. There are currently several single-institution reports and a few multi
      institutional reports on operative, perioperative, and intermediate-term
      oncologic outcomes for RARC. While the data appears promising, there is currently
      no long term oncologic outcomes for RARC. Long-term oncologic outcomes for RARC
      should be forthcoming in the near future. As the technology improves, and
      surgeons become more proficient at RARC, the cost effectiveness of RARC should
      surpass open radical cystectomy. The goal of this article is to review the most
      recent developments within the past 1 to 2 years surrounding RARC, including
      important technical advances for performing this operation, current data on
      oncologic outcomes, and the future direction of RARC.

PMID- 22617304
TI  - Robot-assisted radical prostatectomy: tips, tricks and pitfalls.
AB  - In the last decade, we have assisted to the progressive standardization of the
      surgical technique of robot-assisted radical prostatectomy (RARP). This article
      describes in details our current surgical technique to perform nerve-sparing
      RARP. Specifically, we took in consideration the tips, tricks and pitfalls of
      each step of RARP according to our experience.

PMID- 22617305
TI  - Robotic-assisted surgery and the evolution of the radical prostatectomy.
AB  - The surgical treatment of prostate cancer has evolved considerably since it was
      first described in 1905. With the introduction of a robotic, surgical-assist
      device, minimally invasive techniques for prostate removal have been increasingly
      utilized throughout the world. Currently, there is a large body of literature
      suggesting that robotic-assisted laparoscopic prostatectomy is associated with
      certain improved perioperative and postoperative outcomes and similar cancer
      control rates compared to open radical prostatectomy. The goal of this review is
      to objectively evaluate and describe the current state-of-the-art in surgical
      technique, perioperative and long-term outcomes, complications and the future of
      robotic-assisted laparoscopic radical prostatectomy.

PMID- 22617306
TI  - Interventional therapies for lower urinary tract symptoms (LUTS) suggestive of
      benign prostatic hyperplasia (BPH).
AB  - Benign prostatic hyperplasia (BPH) is a common disease in older men that can lead
      to lower urinary tract symptoms (LUTS). After failure of medical treatment,
      surgical managements has to be considered. Surgical management of lower urinary
      tract symptoms attributed to BPH has progressed over time as urologic surgeons
      search for more innovative and less invasive forms of treatment. Transurethral
      resection of the prostate (TURP) has long been the "gold standard" to which all
      other forms of treatment are compared. There are several different methods of
      surgical treatment of BPH, including whole gland enucleation, laser vaporization,
      and induction of necrosis with delayed reabsorption as well as hybrid techniques.
      As with any form of surgical intervention, long-term results define success. Long
      term follow-up consists of examining overall efficacy with attention to
      associated adverse events. TURP has the luxury of the longest follow-up, while
      less invasive forms of treatment starting to acquire long-term data. There are
      several surgical options for BPH; newer methods do show promise, while the "gold
      standard" continues to demonstrate excellent surgical results.

PMID- 22617307
TI  - [The role of Proxelan in the treatment of chronic prostatitis. Results of a
      randomized trial].
AB  - AIM: Inflammatory diseases of the prostate are one of the most difficult problems
      to manage in the fertile male aged between 20 and 50. Antibiotics are the gold
      standard for the treatment of both bacterial (category II-NIH) and non bacterial
      prostatitis (category III-NIH). However, antibiotics need to be associated with
      other therapies focused on reducing symptoms and providing a better quality of
      life. In the present study we sought to test the effectiveness of antibiotics and
      the medical device Proxelan suppositories taken together. METHODS: Starting in
      January 2011, we conducted a randomized controlled trial involving 60 subjects
      with bacterial and non bacterial chronic prostatitis, who were divided into two
      groups. Subjects allocated in group A received only antibiotics for 28 days;
      subjects in group B received antibiotics + Proxelan, for 28 days as well. Before
      randomization all subjects underwent Meares-Stamey test, IPSS and NIH-CPSI
      questionnairs. All of those were repeated 60 and 120 days after randomization.
      Microbiological and clinical efficacy were compared using specific statistical
      analyses. RESULTS: Data were obtained from 29 subjects allocated in group A and
      31 in group B. Minor side effects were observed which did not cause study
      interruption in any case. Of the total population, 68,3% resulted positive to the
      Meares-Stamey test at study start. Proxelan was not better than antibiotics alone
      under a microbiological point of view (OR)=0.9; (IR) 0.3-2.8; P=0.46. According
      to the answers provided at the NIH-CPSI questionnaire, subjects in the group B
      obtained a better score compared to group A, either after 2 months (OR:2.8; 95%IC
      1.2-4.1; P=0.017) and after 4 months (OR:1.67; 95%IC 0.9-2.9; P=0.04). With
      regards to the IPSS questionnaire, 2 months after treatment start, subjects in
      the group A had a probability of having urinary symptoms 2 times higher compared
      to subjects in group B (OR:1.9; 95%IC 1.0-3.5; P=0.028). Although Proxelan seems
      to improve IPSS also after 4 months, the difference does not reach the level of
      statistical significance. CONCLUSION: Compared to antibiotics alone, the
      combination of antibiotics and Proxelan improve both symptoms associated to
      chronic prostatitis and urinary symptoms, however microbiological results are not
      different. Future studies may be required to confirm our results and to explain
      the mechanism of action of Proxelan.

PMID- 22617308
TI  - Hepsin in the diagnosis of prostate cancer.
AB  - AIM: In the current study we verified whether the expression of hepsin in
      prostate cancer (PCa) of samples obtained from radical retropubic prostatectomies
      (RRP) was significantly different from the adjacent normal prostatic tissue.
      METHODS. We evaluate the expression of hepsin by using immunohistochemistry in
      PCa tissue in respect to the adjacent normal tissue, of 18 patients who underwent
      RRP. RESULTS: Hepsin positive immunoreactivity was estimated on the staining
      intensity as negative (0), weakly positive (1+), moderately positive (2+), and
      strongly positive (3+). Hepsin immunoreactivity was detected in 100.0% PCa: 94.4%
      of cases showed a moderate/strong intensity, 5.6% a weak intensity. The adjacent
      benign prostatic tissue demonstrated a 83.3% of weak intensity, 11.1% had no
      reactivity and 5.6% were moderately intense. PCa demonstrated a significant
      higher (P<0.05) hepsin intensity (2.67) than the adjacent benign tissue (0.94).
      CONCLUSION: Hepsin should be regarded as a novel potential immunohistochemical
      marker for the histopathological diagnosis of PCa.

PMID- 22617309
TI  - A typical Wegeners granulomatosis -- but not pauci-immune!
AB  - We present a the case of 58-year old man who was admitted to hospital with
      typical clinical features (bloody nasal discharge, arthralgia, acute kidney
      injury with a nephritic syndrome) consisting with Wegeners granulomatosis (WG).
      CT-scan showed pulmonary nodules and antineutrophil cytoplasmatic antibodies
      (ANCA) were elevated. A kidney biopsy showed a crescentic glomerulonephritis, but
      not pauci-immune-immune with a histopathological staining of a
      mesangioproliferative IgA-glomerulonephritis. The patient was put on prednisolone
      and i.v. cyclophosphamid (CYCLOPS-protocol (1). The anti-proteinase-3 antibody
      titer decreased and the CT-scan showed decreased activity of Wegener's
      granulomatosis (BVAS 26 dropped to 2) and the patient's serum creatinine level
      was stable. The exact nosological relation of mesangial IgA-nephropathy to WG is
      still unclear. This case underlines that knowledge of renal histology is
      essential in the management of patients with renal disease, especially in
      patients with hematuria and/or proeinuria with positive ANCA.

PMID- 22617311
TI  - Effect of cognitive load on working memory forgetting in aging.
AB  - Functional approaches to working memory (WM) have been proposed recently to
      better investigate "maintenance" and "processing" mechanisms. The cognitive load
      (CL) hypothesis presented in the "Time-Based Resource-Sharing" model (Barrouillet
      & Camos, 2007) suggests that forgetting from WM (maintenance) can be investigated
      by varying the presentation rate and processing speed (processing). In this
      study, young and elderly participants were compared on WM tasks in which the
      difference in processing speed was controlled by CL manipulations. Two main
      results were found. First, when time constraints (CL) were matched for the two
      groups, no aging effect was observed. Second, whereas a large variation in CL
      affected WM performance, a small CL manipulation had no effect on the elderly.
      This suggests that WM forgetting cannot be completely accounted for by the CL
      hypothesis. Rather, it highlights the need to explore restoration times in
      particular, and the nature of the refreshment mechanisms within maintenance.

PMID- 22617312
TI  - Sequential difficulty effects during strategy execution.
AB  - In two experiments, we tested the hypothesis that strategy performance on a given
      trial is influenced by the difficulty of the strategy executed on the immediately
      preceding trial, an effect that we call strategy sequential difficulty effect.
      Participants' task was to provide approximate sums to two-digit addition problems
      by using cued rounding strategies. Results showed that performance was poorer
      after a difficult strategy than after an easy strategy. Our results have
      important theoretical and empirical implications for computational models of
      strategy choices and for furthering our understanding of strategic variations in
      arithmetic as well as in human cognition in general.

PMID- 22617310
TI  - Neural and metabolic regulation of macronutrient intake and selection.
AB  - There is considerable disagreement regarding what constitutes a healthy diet.
      Ever since the influential work of Cannon and Richter, it was debated whether the
      'wisdom of the body' will automatically direct us to the foods we need for
      healthy lives or whether we must carefully learn to eat the right foods,
      particularly in an environment of plenty. Although it is clear that strong
      mechanisms have evolved to prevent consumption of foods that have previously made
      us sick, it is less clear whether reciprocal mechanisms exist that reinforce the
      consumption of healthy diets. Here, we review recent progress in providing
      behavioural evidence for the regulation of intake and selection of proteins,
      carbohydrates and fats. We examine new developments in sensory physiology
      enabling recognition of macronutrients both pre- and post-ingestively. Finally,
      we propose a general model for central neural processing of nutrient-specific
      appetites. We suggest that the same basic neural circuitry responsible for the
      homoeostatic regulation of total energy intake is also used to control
      consumption of specific macro- and micronutrients. Similar to salt appetite,
      specific appetites for other micro- and macronutrients may be encoded by unique
      molecular changes in the hypothalamus. Gratification of such specific appetites
      is then accomplished by engaging the brain motivational system to assign the
      highest reward prediction to exteroceptive cues previously associated with
      consuming the missing ingredient. A better understanding of these nutrient
      specific neural processes could help design drugs and behavioural strategies that
      promote healthier eating.

PMID- 22617313
TI  - Visuospatial perceptual sequence learning and eye movements.
AB  - We examined perceptual sequence learning by means of an adapted serial reaction
      time task in which eye movements were unnecessary for performing the sequence
      learning task. Participants had to respond to the identity of a target letter
      pair ("OX" or "XO") appearing in one of four locations. On the other locations,
      similar distractor letter pairs ("QY" or "YQ") were shown. While target identity
      changed randomly, target location was structured according to a deterministic
      sequence. To render eye movements superfluous, (1) stimulus letter pairs appeared
      around a fixation cross with a visual angle of 0.63 degrees , which means that
      they appeared within the foveal visual area and (2) the letter pairs were
      presented for only 100 ms, a period too short to allow proper eye movements.
      Reliable sequence knowledge was acquired under these conditions, as responses
      were both slower and less accurate when the trained sequence was replaced by an
      untrained sequence. These results support the notion that perceptual sequence
      learning can be based on shifts of attention without overt oculomotor movements.

PMID- 22617314
TI  - Priming of future states in complex motor skills.
AB  - The ability to anticipate future states of perceived actions is an important
      faculty for motor control and the generation of coordinated social interaction.
      Here, we studied whether the perception of a static posture of a complex movement
      automatically activates representations of future states of this particular
      movement event. We did this by using a priming paradigm with photographs of a
      high-jump movement. Participants judged whether a picture depicted a posture from
      the approach or flight phase of that movement. To evaluate expertise-dependent
      effects of priming, non-athletes and athletes were compared. Results revealed
      faster responding when prime and target pictures were assigned to the same motor
      response (response priming), and when the temporal order of prime and target
      matched the temporal order of the depicted postures in a real high jump (temporal
      order priming). Whereas experts showed a temporal-order effect even within the
      same response category, such an effect occurred for novices only between response
      categories. A second experiment confirmed that these between-group differences
      are due to domain-specific motor expertise (i.e., high jump) rather than to
      general motor experiences. Altogether our results suggest that motor expertise
      results in a more fine-grained posture-based movement representation.

PMID- 22617315
TI  - Phasic affective modulation of creativity.
AB  - Thus far, it has been shown that positive compared to negative mood increases
      creativity, for instance, as measured by performance in the remote associate
      task, where participants are asked to find the common remote associate for three
      clue words (e.g., RABBIT CLOUD MILK solution word WHITE). The present experiments
      show that very brief variations in affect, lasting for only a few seconds and
      changing from trial to trial within participants, are sufficient to modulate
      creativity in that task, presumably by modulating the breadth of semantic spread.
      Using word valence of remote associates themselves (Experiment 1), and consonant
      and dissonant chords (Experiment 2) as affect inductions, it was observed that
      brief positive compared to negative affect increased creative performance. This
      evidence extends the affect-modulation hypothesis to a temporal micro-level.

PMID- 22617316
TI  - A unique asymmetrical stroop effect in absolute pitch possessors.
AB  - The Stroop task has been employed to study automaticity or failures of selective
      attention for many years. The effect is known to be asymmetrical, with words
      affecting color naming but not vice versa. In the current work two auditory
      visual Stroop-like tasks were devised in order to study the automaticity of pitch
      processing in both absolute pitch (AP) possessors and musically trained controls
      without AP (nAP). In the tone naming task, participants were asked to name the
      auditory tone while ignoring a visual note name. In the note naming task,
      participants were asked to read a note name while ignoring the auditory tone. The
      nAP group showed a significant congruency effect only in the tone naming task,
      whereas AP possessors showed the reverse pattern, with a significant congruency
      effect only in the note reading task. Thus, AP possessors were unable to ignore
      the auditory tone when asked to read the note, but were unaffected by the verbal
      note name when asked to label the auditory tone. The results suggest that pitch
      identification in participants endowed with AP ability is automatic and
      impossible to suppress.

PMID- 22617317
TI  - Multiple origins of allopolyploid wheatgrass Elymus caninus revealed by RPB2,
      PepC and TrnD/T genes.
AB  - We examined evolutionary mechanisms in the tetraploid Elymus caninus by comparing
      the phylogenetic relationships of 21 accessions suggested by sequence data from
      two single copy nuclear genes, the largest subunit of RNA polymerase II (RPB2)
      and phosphoenolpyruvate carboxylase (pepC), and one non-coding chloroplast
      region, TrnD/T. Elymus caninus is known combining two different genomes, an St
      genome and an H genome. Data from two single copy nuclear genes showed that there
      are two versions of the St genome in the species, St1 and St2. Most accessions
      combined one of these versions with an H genome version but two accessions had
      both versions of the St sequence for RPB2. This suggests that the RPB2gene may
      have been duplicated without chromosome doubling, possibly induced by
      transposable element. Our data also indicate that the H genome sequences in E.
      caninus have multiple origins, and a close phylogenetic relationship between
      Hordeum bogdanii and H sequences in some accessions of E. caninus. Thus, it is
      more likely that H. bogdanii is one of the major donors of the H copy in E.
      caninus. The maternal origin of E. caninus is the St genome species. There was no
      correlation between the geographic origin of the accessions and their sequence
      divergence.

PMID- 22617318
TI  - Uncoupling of K+ and Cl- transport across the cell membrane in the process of
      regulatory volume decrease.
AB  - It is accepted that K(+) and Cl(-) flows are coupled tightly in regulatory volume
      decrease (RVD). However, using self referencing microelectrodes, we proved that
      K(+) and Cl(-) transport mainly by channels in RVD was uncoupled in
      nasopharyngeal carcinoma CNE-2Z cells, with the transient K(+) efflux activated
      earlier and sustained Cl(-) efflux activated later. Hypotonic challenges
      decreased intracellular pH (pH(i)), and activated a proton pump-dependent H(+)
      efflux, resulting in a decline of extracellular pH (pH(o)). Modest decreases of
      pH(o) inhibited the volume-activated K(+) outflow and RVD, but not the Cl(-)
      outflow, while inhibition of H(+) efflux or increase of pH(o) buffer ability
      promoted K(+) efflux and RVD. The results suggest that the temporal dynamics of
      K(+) channel activities is different from that of Cl(-) channels in RVD, due to
      differential sensitivity of K(+) and Cl(-) channels to pH(o). H(+) efflux may
      play important roles in cell volume regulation, and may be a therapeutic target
      for human nasopharyngeal carcinoma.

PMID- 22617319
TI  - Cost-effectiveness of venous thromboembolism prophylaxis with a new mobile device
      after total hip arthroplasty.
AB  - Recent comparison (SAFE study) of a mobile, synchronized compression device and
      low-molecular-weight heparin for prophylaxis of venous thromboembolism showed
      similar efficacy but significant differences in major bleeding. A model was
      constructed to evaluate any difference in cost-effectiveness between the 2
      therapies incorporating rates and probabilities of major bleeding from the SAFE
      study with published costs for treating those adverse events. Evaluation of the
      cost-effectiveness of each therapy was performed and applied to hypothetical
      patient populations representative of annual health system volume. The model
      showed a cost-effectiveness advantage of the compression device resulting in a
      savings of more than $3.69 million in a 10 000-patient cohort. The result was
      primarily driven by a decrease in the amount of major bleeding, which requires
      significant health care resources to treat.

PMID- 22617320
TI  - Europium-doped gadolinium sulfide nanoparticles as a dual-mode imaging agent for
      T1-weighted MR and photoluminescence imaging.
AB  - We present a facile synthesis of europium-doped gadolinium sulfide (GdS:Eu(3+))
      opto-magnetic nanoparticles (NPs) via sonochemistry. Their photoluminescence and
      strong paramagnetic properties enable these NPs to be utilized as an in vitro
      cell imaging and in vivo T(1)-weighted MR imaging probe. The GdS:Eu(3+) NPs have
      a prominent longitudinal (r(1)) relaxivity value, which is a critical parameter
      for T(1)-weighted MR imaging. Here, we showed not only their strong positive
      contrast effect to blood vessels and organs of mice, but also blood half-life and
      biodistribution including clearance from organs, in order to assess the
      GdS:Eu(3+) NPs as a competent nanocrystal-based T(1) contrast agent. We further
      showed confocal images of breast cancer cells containing GdS:Eu(3+) NPs to
      evaluate as a photoluminescence probe. Dual-mode imaging capability obtained from
      the GdS:Eu(3+) NPs will allow target-oriented cellular imaging as well as the
      resulting disease-specific MR imaging.

PMID- 22617322
TI  - Electronic health record systems and intent to apply for meaningful use
      incentives among office-based physician practices: United States, 2001-2011.
AB  - An increasing trend in EMR/EHR system use among office-based physicians was noted
      from 2001 through preliminary 2011 estimates. In 2011, the NAMCS mail survey
      showed about 57% of office-based physicians used any EMR/EHR system, a 12%
      increase from the 2010 estimate. Between 2010 and 2011, the percentage of
      physicians who reported having systems meeting the criteria for a basic system
      increased 36%. Adoption of EMR/EHR systems varied greatly by state. In 2011, the
      percentage of physicians using any EMR/EHR system ranged from 40% in Louisiana to
      84% in North Dakota. Compared with the national average, 3 states had a
      significantly lower percentage of office-based physicians using any EMR/EHR
      system, and 11 states had a significantly higher percentage. The percentage of
      physicians having a system that met the criteria for a basic system ranged from
      16% in New Jersey to 61% in Minnesota. Compared with the national average, six
      states had a significantly lower percentage of office-based physicians with a
      basic system, and eight states had a significantly higher percentage. In 2011,
      52% of physicians reported intending to apply for the Medicare or Medicaid EHR
      incentive payments, a 26% increase from 2010. In 2010, interest among physicians
      in applying for meaningful use incentive payments was similar to the national
      average (41%) across most states. In only four states (Alaska, New York, North
      Dakota, and West Virginia) and the District of Columbia was the percentage lower
      than the national average. To qualify for Stage 1 meaningful use incentive
      payments, eligible physicians need to meet all 15 Stage 1 Core Set objectives and
      5 of 10 Menu Set objectives, using certified EHR systems (see "Definitions"). In
      this report, estimates of physicians' readiness to meet Stage 1 Core Set
      meaningful use measures were limited to data collected on the computerized
      functions needed to meet eight Stage 1 objectives. A previous study found that
      15% of physicians eligible to apply for meaningful use incentives had EHR systems
      with basic functions capability (3). In the present study, 43% of physicians
      planning to apply for incentives had EHR systems with functions that would allow
      them to meet eight Stage 1 Core Set meaningful use objectives. In 2010, the
      percentage of physicians planning to apply for incentives with EHR systems able
      to support eight Stage 1 Core Set objectives exceeded the national average in
      eight states (Iowa, Maine, Massachusetts, Minnesota, Oregon, Utah, Washington,
      and Wisconsin) and was below the national average only in Texas. The 2010
      estimates represent an overestimate of physician readiness because not all
      physicians with systems supporting all eight objectives examined in this report
      have systems also capable of supporting the remaining seven Core Set objectives
      and 5 of 10 Menu Set objectives required for payment. As federal programs to
      provide incentives for meaningful use and local technical support are
      implemented, monitoring EHR system adoption will continue to be important in
      evaluating the effectiveness of these policies and targeting efforts in certain
      areas.

PMID- 22617321
TI  - Superparamagnetic PLGA-iron oxide microcapsules for dual-modality US/MR imaging
      and high intensity focused US breast cancer ablation.
AB  - Organic/inorganic, hybrid, multifunctional, material-based platforms combine the
      merits of diverse functionalities of inorganic nanoparticles and the excellent
      biocompatibility of organic systems. In this work, superparamagnetic poly(lactic
      co-glycolic acid) (PLGA) microcapsules (Fe(3)O(4)/PLGA) have been developed, as a
      proof-of-concept, for the application in ultrasound/magnetic resonance dual
      modality biological imaging and enhancing the therapeutic efficiency of high
      intensity focused ultrasound (HIFU) breast cancer surgery in vitro and in vivo.
      Hydrophobic Fe(3)O(4) nanoparticles were successfully integrated into PLGA
      microcapsules by a typical double emulsion evaporation process. In this process,
      highly dispersed superparamagnetic Fe(3)O(4)/PLGA composite microcapsules with
      well-defined spherical morphology were obtained with an average diameter of 885.6
      nm. The potential of these microcapsules as dual contrast agents for
      ultrasonography and magnetic resonance imaging were demonstrated in vitro and,
      also, preliminarily in vivo. Meanwhile, the prepared superparamagnetic composite
      microcapsules were administrated into rabbits bearing breast cancer model for the
      evaluation of the in vivo HIFU synergistic ablation efficiency caused by the
      introduction of such microcapsules. Our results showed that the employment of the
      composite microcapsules could efficiently enhance ultrasound imaging of cancer,
      and greatly enhance the HIFU ablation of breast cancer in rabbits. In addition,
      pathological examination was systematically performed to detect the structural
      changes of the target tissue caused by HIFU ablation. This finding demonstrated
      that successful introduction of these superparamagnetic microcapsules into HIFU
      cancer surgery provided an alternative strategy for the highly efficient imaging
      guided non-invasive HIFU synergistic therapy of cancer.

PMID- 22617324
TI  - Functionalization of reduced graphene oxides by redox-active ionic liquids for
      energy storage.
AB  - The reduced graphene oxides (RGOs) functionalized by pyridinium-based ionic
      liquids (ILs) with SCN anions revealed 6-fold higher capacitance compared to that
      of RGOs due to the redox behavior of ILs as well as good rate capability and
      cycle stability despite the appearance of pseudo-capacitance.

PMID- 22617325
TI  - MET signaling regulates glioblastoma stem cells.
AB  - Glioblastomas multiforme (GBM) contain highly tumorigenic, self-renewing
      populations of stem/initiating cells [glioblastoma stem cells (GSC)] that
      contribute to tumor propagation and treatment resistance. However, our knowledge
      of the specific signaling pathways that regulate GSCs is limited. The MET
      tyrosine kinase is known to stimulate the survival, proliferation, and invasion
      of various cancers including GBM. Here, we identified a distinct fraction of
      cells expressing a high level of MET in human primary GBM specimens that were
      preferentially localized in perivascular regions of human GBM biopsy tissues and
      were found to be highly clonogenic, tumorigenic, and resistant to radiation.
      Inhibition of MET signaling in GSCs disrupted tumor growth and invasiveness both
      in vitro and in vivo, suggesting that MET activation is required for GSCs.
      Together, our findings indicate that MET activation in GBM is a functional
      requisite for the cancer stem cell phenotype and a promising therapeutic target.

PMID- 22617326
TI  - Perturbation of Rb, p53, and Brca1 or Brca2 cooperate in inducing metastatic
      serous epithelial ovarian cancer.
AB  - The majority of human high-grade serous epithelial ovarian cancer (SEOC) is
      characterized by frequent mutations in p53 and alterations in the RB and FOXM1
      pathways. A subset of human SEOC harbors a combination of germline and somatic
      mutations as well as epigenetic dysfunction for BRCA1/2. Using Cre-conditional
      alleles and intrabursal induction by Cre-expressing adenovirus in genetically
      engineered mice, we analyzed the roles of pathway perturbations in epithelial
      ovarian cancer initiation and progression. Inactivation of RB-mediated tumor
      suppression induced surface epithelial proliferation with progression to stage I
      carcinoma. Additional biallelic inactivation and/or missense p53 mutation in the
      presence or absence of Brca1/2 caused progression to stage IV disease. As in
      human SEOC, mice developed peritoneal carcinomatosis, ascites, and distant
      metastases. Unbiased gene expression and metabolomic profiling confirmed that Rb,
      p53, and Brca1/2-triple mutant tumors aligned with human SEOC, and not with other
      intraperitoneal cancers. Together, our findings provide a novel resource for
      evaluating disease etiology and biomarkers, therapeutic evaluation, and improved
      imaging strategies in epithelial ovarian cancer.

PMID- 22617327
TI  - Role of N-terminal myristylation in the structure and regulation of cAMP
      dependent protein kinase.
AB  - The catalytic (C) subunit of cAMP-dependent protein kinase [protein kinase A
      (PKA)] is a major target of cAMP signaling, and its regulation is of fundamental
      importance to biological processes. One mode of regulation is N-myristylation,
      which has eluded structural and functional characterization so far because most
      crystal structures are of the non-myristylated enzyme, are phosphorylated on
      Ser10, and generally lack electron density for the first 13 residues. We
      crystallized myristylated wild-type (WT) PKA and a K7C mutant as binary (bound to
      a substrate peptide) and ternary [bound to a substrate peptide and adenosine-5'
      (beta,gamma-imido)triphosphate] complexes. There was clear electron density for
      the entire N-terminus in the binary complexes, both refined to 2.0 A, and K7C
      ternary complex, refined to 1.35 A. The N-termini in these three structures
      display a novel conformation with a previously unseen helix from residues 1 to 7.
      The K7C mutant appears to have a more stable N-terminus, and this correlated with
      a significant decrease in the B-factors for the N-terminus in the myr-K7C
      complexes compared to the WT binary complex. The N-terminus of the myristylated
      WT ternary complex, refined to 2.0 A, was disordered as in previous structures.
      In addition to a more ordered N-terminus, the myristylated K7C mutant exhibited a
      53% increase in k(cat). The effect of nucleotide binding on the structure of the
      N-terminus in the WT protein and the kinetic changes in the K7C protein suggest
      that myristylation or occupancy of the myristyl binding pocket may serve as a
      site for allosteric regulation in the C-subunit.

PMID- 22617329
TI  - The preservation of alveolar bone ridge during tooth extraction.
AB  - OBJECTIVES: The aims were to overview healing of extraction socket,
      recommendations for atraumatic tooth extraction, possibilities of post extraction
      socket bone and soft tissues preservation, augmentation. MATERIALS AND METHODS: A
      search was done in Pubmed on key words in English from 1962 to December 2011.
      Additionally, last decades different scientific publications, books from
      reference list were assessed for appropriate review if relevant. RESULTS AND
      CONCLUSIONS: There was made intraalveolar and extraalveolar postextractional
      socket healing overview. There was established the importance and effectiveness
      of atraumatic tooth extraction and subsequent postextractional socket
      augmentation in limited hard and soft tissue defects. There are many different
      methods, techniques, periods, materials in regard to the review. It is difficult
      to compare the data and to give the priority to one.

PMID- 22617328
TI  - Predictive Bcl-2 family binding models rooted in experiment or structure.
AB  - Proteins of the Bcl-2 family either enhance or suppress programmed cell death and
      are centrally involved in cancer development and resistance to chemotherapy. BH3
      (Bcl-2 homology 3)-only Bcl-2 proteins promote cell death by docking an alpha
      helix into a hydrophobic groove on the surface of one or more of five pro
      survival Bcl-2 receptor proteins. There is high structural homology within the
      pro-death and pro-survival families, yet a high degree of interaction specificity
      is nevertheless encoded, posing an interesting and important molecular
      recognition problem. Understanding protein features that dictate Bcl-2
      interaction specificity is critical for designing peptide-based cancer
      therapeutics and diagnostics. In this study, we present peptide SPOT arrays and
      deep sequencing data from yeast display screening experiments that significantly
      expand the BH3 sequence space that has been experimentally tested for interaction
      with five human anti-apoptotic receptors. These data provide rich information
      about the determinants of Bcl-2 family specificity. To interpret and use the
      information, we constructed two simple data-based models that can predict
      affinity and specificity when evaluated on independent data sets within a limited
      sequence space. We also constructed a novel structure-based statistical
      potential, called STATIUM, which is remarkably good at predicting Bcl-2 affinity
      and specificity, especially considering it is not trained on experimental data.
      We compare the performance of our three models to each other and to alternative
      structure-based methods and discuss how such tools can guide prediction and
      design of new Bcl-2 family complexes.

PMID- 22617330
TI  - Evidence based toothpaste classification, according to certain characteristics of
      their chemical composition.
AB  - Toothpastes are daily oral care products, the chemical composition of which is
      constantly changing due to manufacturer's competition. It becomes more and more
      difficult for dentists to recommend the best toothpaste and for patients to
      choose one. The objective of this paper was to draw out recommendations based on
      the best evidence available and to propose a new classification of toothpastes.
      Publications were searched in PubMed database (published between 1991-2011,
      limited to English language articles in dental journals). Recommendations for
      toothpaste choice and usage were developed from the best evidence available.

PMID- 22617331
TI  - Quantity and quality analysis of dental prosthodontics among retirement age
      residents from nursing homes in different regions of Latvia and retirement age
      patients from dental clinic in Riga.
AB  - INTRODUCTION: The quality of life is closely related with condition of oral
      health, influence of subjective factors on the whole human body and patients
      perception of their oral health. In spite of the fact that the most part of
      Latvian retirement age residents use low-quality dentures and assess them
      satisfactory, these patients often have problems associated with quality of
      dentures. The aim of the present study was to evaluate oral health status,
      prosthodontics indicators and patients satisfaction with oral health among
      Latvian retirement age residents. PATIENTS AND METHODS: There were examined 465
      retirement age volunteers (170 men and 295 women), 116 of them in dental clinic
      Sandent (Riga, 24.9% - control group), 137 (29.5%) in nursing homes in Zemgale
      and 212 (45.6%) in nursing homes in Kurzeme (Zemgale and Kurzeme are districts of
      Latvia). There were assessed quantity of prosthodontics among patients with
      partial defects of dental arches, there were estimated quality of dentures and
      patients satisfaction with existing prosthodontics. RESULTS: Oral health
      indicators among Latvian retirement age population are better than the same
      indicators among elderly residents of nursing homes. Among nursing homes
      residents with partial edentulousness in most of cases in oral cavities remained
      only few residual teeth which needed treatment. Removable and fixed dental
      prostheses used by nursing homes residents do not meet denture's quality
      criteria. Self-evaluation of dentures quality among retirement age residents of
      nursing homes is better and not correspond with existing dentures quality.
      CONCLUSIONS: In Latvia the quantity of prosthodontics in respect of partial
      removable dentures among the retired who regularly visit a dentist does not
      significantly differ from European retirement age population's dental
      prosthodontics quantity. Dental prosthodontics indicators of residents of nursing
      homes in Latvia are unsatisfactory (p<0.001). In retirement age population self
      evaluation with quality of dentures is higher than actually existing.

PMID- 22617332
TI  - Occupational hazards and preventive practices among students and faculty at a
      private dental institution in India.
AB  - AIMS: To assess the level of awareness and occupational hazards experienced in
      addition to preventive measures undertaken by the students and faculty working at
      a private dental institution in India. METHODS: The present study was conducted
      at a private dental teaching hospital in India using self-administered
      questionnaires. All the students attending the clinics and the faculty members of
      the hospital were invited to participate in the study. The final study population
      consisted of 290 dental professionals. The self-administered questionnaire also
      included questions on personal information like age, gender, position (student or
      faculty), years of experience and number of working hours per day apart from the
      questions on the level of awareness, preventive procedures undertaken and
      occupational hazards experienced. RESULTS: Significantly greater number of
      females experienced musculoskeletal disorders (p=0.031) and allergy to latex
      (p=0.004) than males. Nearly half the study population reported of sharp
      instrument injury while treating the patients. The most prevalent preventive
      measure reported by the respondents was changing gloves between the patients
      (98.6%) and use of face mask (97.2%). Most of the participants (94.1%) had
      undergone Hepatitis B or other vaccination procedures. CONCLUSIONS: Majority of
      the study population were aware of the biological hazards associated with the
      practice of dentistry. None of the preventive measures were observed by all the
      participants.

PMID- 22617333
TI  - Conservative treatment of ameloblastoma in child: a case report.
AB  - Ameloblastoma is the common form of aggressive benign tumor of the jaws, but it
      is rare in childhood. The treatment of ameloblastoma is controversial. Surgical
      treatment of ameloblastoma in children follows the principles of the clinical and
      pathological aspects of the tumor and poses a special problem due to the
      incomplete growth of the jaws. With a unicystic ameloblastoma, the procedure of
      choice is a conservative approach. This paper describes the conservative
      treatment of a plexiform unicystic ameloblastoma in a child involving curettage
      of the tumor and the extraction of two teeth under local anesthesia, with a good
      prognosis of the case.

PMID- 22617334
TI  - Phospho-Bcl-x(L)(Ser62) plays a key role at DNA damage-induced G(2) checkpoint.
AB  - Accumulating evidence suggests that Bcl-xL, an anti-apoptotic member of the Bcl-2
      family, also functions in cell cycle progression and cell cycle checkpoints.
      Analysis of a series of phosphorylation site mutants reveals that cells
      expressing Bcl-xL(Ser62Ala) mutant are less stable at the G 2 checkpoint and
      enter mitosis more rapidly than cells expressing wild-type Bcl-xL or Bcl-xL
      phosphorylation site mutants, including Thr41Ala, Ser43Ala, Thr47Ala, Ser56Ala
      and Thr115Ala. Analysis of the dynamic phosphorylation and location of phospho
      Bcl-xL(Ser62) in unperturbed, synchronized cells and during DNA damage-induced G
      2 arrest discloses that a pool of phospho-Bcl-xL(Ser62) accumulates into
      nucleolar structures in etoposide-exposed cells during G 2 arrest. In a series of
      in vitro kinase assays, pharmacological inhibitors and specific siRNAs
      experiments, we found that Polo kinase 1 and MAPK9/JNK2 are major protein kinases
      involved in Bcl-xL(Ser62) phosphorylation and accumulation into nucleolar
      structures during the G 2 checkpoint. In nucleoli, phospho-Bcl-xL(Ser62) binds to
      and co-localizes with Cdk1(cdc2), the key cyclin-dependent kinase required for
      entry into mitosis. These data indicate that during G 2 checkpoint, phospho-Bcl
      xL(Ser62) stabilizes G 2 arrest by timely trapping of Cdk1(cdc2) in nucleolar
      structures to slow mitotic entry. It also highlights that DNA damage affects the
      dynamic composition of the nucleolus, which now emerges as a piece of the DNA
      damage response.

PMID- 22617335
TI  - A heterochromatin protein 1 (HP1) dimer and a proliferating cell nuclear antigen
      (PCNA) protein interact in vivo and are parts of a multiprotein complex involved
      in DNA replication and DNA repair.
AB  - Heterochromatin protein 1 (HP1) is a small non-histone chromosomal protein known
      as a dominant suppressor of position-effect variegation and a major component of
      heterochromatin. Posttranslationally modified HP1, through interaction with
      protein partners from different groups, can be involved in a number of nuclear
      processes, including gene activation, chromatin remodeling, replication and DNA
      repair. Using bimolecular fluorescence complementation assay and live cell
      imaging, we demonstrate that HP1beta and PCNA, a key player in DNA replication,
      are closely spaced components of a multiprotein complex involved in replication,
      both in S phase and during DNA repair, and that the functional complex requires
      formation of an HP1 dimer.

PMID- 22617336
TI  - Coronary artery vitamin D receptor expression and plasma concentrations of 25
      hydroxyvitamin D:  their association with atherosclerosis.
AB  - OBJECTIVE: The aim of this study was to analyze coronary artery vitamin D
      receptor (VDR) expression, the plasma concentrations of 25-hydroxyvitamin D3
      (25OHD3), and their relationship with coronary artery atherosclerosis. METHODS:
      Premenopausal cynomolgus monkeys were fed atherogenic diets containing the
      equivalent of 1,000 IU/day of vitamin D3. Protein was derived from casein
      lactalbumin (C/L, n = 10), soy protein isolate (soy, n = 10), or a combination (n
      = 19). After 32 months of consuming the diets, each monkey underwent surgical
      menopause. After 32 postmenopausal months, coronary atherosclerosis was measured
      in the left circumflex (LCX) artery and left anterior descending (LAD) artery.
      VDR expression was determined for the LAD, and 25OHD3 concentrations were
      assessed. RESULTS: Both the cross-sectional area of atherosclerotic plaques (in
      square millimeters) and plaque thickness (in millimeters) in the LCX as well as
      the LAD arteries were analyzed in these monkeys. Those with higher plasma vitamin
      D3 concentrations and higher VDR were compared with those with higher plasma
      25OHD3 concentrations and lower VDR. Significantly smaller plaque sizes were
      noted with higher plasma 25OHD3 concentrations and higher VDR. For the LCX
      artery, there was also a significantly lower plaque size (both plaque thickness
      and cross-sectional area) in those with higher quantities of VDR and lower 25OHD3
      concentrations versus those with lower quantities of VDR and higher plasma
      concentrations of 25OHD3 (P = 0.009 and P = 0.040, respectively). CONCLUSIONS:
      Cynomolgus monkeys with higher quantities of VDR have significantly less
      atherosclerosis than do those with lower quantities of VDR and higher plasma
      25OHD3 concentrations. If these findings translate to human beings, it might
      explain why some individuals with higher plasma concentrations of 25OHD3 have
      more coronary artery atherosclerosis.

PMID- 22617338
TI  - Phylogeography of Lyme borreliosis-group spirochetes and methicillin-resistant
      Staphylococcus aureus.
AB  - Multilocus sequence typing (MLST) and multilocus sequence analysis (MLSA) have
      revolutionized understanding the global epidemiology of many medically relevant
      bacteria utilizing a number, mostly seven, of housekeeping genes. A more recent
      introduction, single nucleotide polymorphisms (SNPs), constitutes an even more
      powerful tool for bacterial typing, population genetic studies and
      phylogeography. The introduction of massive parallel sequencing has made genome
      re-sequencing and SNP discovery more economical for investigations of microbial
      organisms. In this paper we review phylogeographic studies on Lyme borreliosis
      (LB)-group spirochetes and methicillin-resistant Staphylococcus aureus (MRSA).
      Members of the LB-group spirochetes are tick-transmitted zoonotic bacteria that
      have many hosts and differ in their degree of host specialism, constituting a
      highly complex system. MRSA is a directly transmitted pathogen that may be
      acquired by contact with infected people, animals or MRSA-contaminated objects.
      For the LB-group spirochetes, MLSA has proved a powerful tool for species
      assignment and phylogeographic investigations while for S. aureus, genome-wide
      SNP data have been used to study the very short-term evolution of two important
      MRSA lineages, ST239 and ST225. These data are detailed in this review.

PMID- 22617337
TI  - Effects of long-term treatment with estrogen and medroxyprogesterone acetate on
      synapse number in the medial prefrontal cortex of aged female rats.
AB  - OBJECTIVE: The present study investigated the effects of long-term hormone
      treatment, including the most commonly prescribed progestin, medroxyprogesterone
      acetate, during aging on synaptophysin-labeled boutons, a marker of synapses, in
      the medial prefrontal cortex (mPFC) of rats. METHODS: Female Long Evans hooded
      rats were ovariectomized at middle age (12-13 mo) and were placed in one of four
      groups: no replacement (n = 5), 17beta-estradiol alone (n = 6), estradiol and
      progesterone (n = 7), or estradiol and medroxyprogesterone acetate (n = 4).
      Estradiol was administered in the drinking water and progestogens were
      administered via subcutaneous pellets that were replaced every 90 days. After 7
      months of hormone replacement, the animals were euthanized, and the brains were
      stained for synaptophysin, a membrane component of synaptic vesicles. The density
      of synaptophysin-labeled boutons was quantified in the mPFC using unbiased
      stereology and multiplied by the volume of the mPFC to obtain the total number.
      RESULTS: Animals receiving estradiol and medroxyprogesterone acetate had
      significantly more synaptophysin-labeled boutons in the mPFC than did animals not
      receiving replacement (P < 0.03) and those receiving estradiol and progesterone
      (P < 0.02). In addition, there was a nonsignificant trend for animals receiving
      estradiol alone to have more synapses than those receiving estradiol and
      progesterone. CONCLUSIONS: This study is the first to examine the effects of
      estradiol and medroxyprogesterone acetate during rat aging on cortical synaptic
      number. Estradiol with medroxyprogesterone acetate, but not progesterone,
      resulted in a greater number of synapses in the mPFC during aging than did no
      replacement.

PMID- 22617339
TI  - iSpike: a spiking neural interface for the iCub robot.
AB  - This paper presents iSpike: a C++ library that interfaces between spiking neural
      network simulators and the iCub humanoid robot. It uses a biologically inspired
      approach to convert the robot's sensory information into spikes that are passed
      to the neural network simulator, and it decodes output spikes from the network
      into motor signals that are sent to control the robot. Applications of iSpike
      range from embodied models of the brain to the development of intelligent robots
      using biologically inspired spiking neural networks. iSpike is an open source
      library that is available for free download under the terms of the GPL.

PMID- 22617340
TI  - Trends in asthma prevalence, health care use, and mortality in the United States,
      2001-2010.
AB  - Asthma prevalence increased from 2001 to 2010: An estimated 25.7 million persons
      had asthma in 2010. Certain demographic groups had higher asthma prevalence:
      children aged 0-17 years, females, black persons, persons of multiple race,
      Puerto Rican persons, and persons with a family income below the poverty level.
      This report examines rates for asthma outcomes (health care encounters and death)
      for persons with asthma rather than for the general population. Rates for the
      general population represent the burden of asthma in the United States. Rates for
      the population with asthma take into account changes in asthma prevalence over
      time and differences in asthma prevalence among demographic groups. From 2001 to
      2009, rates for ED visits and hospitalizations per 100 persons with asthma
      remained stable, while rates for asthma visits in primary care settings
      (physician offices or hospital outpatient departments) and asthma deaths
      declined. For the period 2007-2009, asthma visit rates (per 100 persons with
      asthma) in primary care settings for black persons were similar to those for
      white persons, but rates for asthma ED visits, hospitalizations, and death (per
      1,000) were higher. Compared with adults, children aged 0-17 years had a higher
      rate for asthma visits in primary care settings and EDs, but had a similar
      hospitalization rate and a lower asthma death rate.

PMID- 22617341
TI  - Plasma pentraxin-3 levels are associated with coronary plaque vulnerability and
      are decreased by statin.
AB  - OBJECTIVE: Pentraxin 3 (PTX3) is a novel candidate immunoinflammatory marker that
      has been reported to be associated with cardiometabolic risk factors and to
      predict adverse outcomes in patients with coronary artery disease. The purpose of
      this study was to investigate the association between the plasma levels of PTX3
      and plaque vulnerability and the effect of the levels using statin in patients
      with coronary artery disease. METHODS: We determined the associations among the
      plasma levels of PTX3 and coronary plaque vulnerability in nonculprit coronary
      lesions with stenosis as assessed by integrated backscatter intravascular
      ultrasound (study 1). One hundred and eighteen consecutive patients with stable
      angina who underwent a percutaneous coronary intervention were enrolled. We also
      enrolled 53 patients with stable angina, and they were treated either with (n=36)
      or without (n=17) atorvastatin (10 mg/day) (study 2). RESULTS: In study 1,
      although there was no association between the plasma levels of PTX3 and plaque
      vulnerability in all patients, the level of PTX3 was positively correlated with
      the percentage of lipid volume and negatively correlated with the percentage of
      fibrous volume in patients without statin treatment. There were no associations
      between high-sensitivity C-reactive protein levels and percentage of lipid volume
      and fibrous volume. Moreover, in study 2, statin therapy for 6-8 months
      significantly decreased the level of PTX3 in addition to high-sensitivity C
      reactive protein. CONCLUSION: The plasma level of PTX3 may be a useful biomarker
      for predicting the tissue characteristics of coronary plaque using integrated
      backscatter intravascular ultrasound. Statin therapy may have a beneficial effect
      with regard to the reduction of PTX3 levels.

PMID- 22617342
TI  - Effect of mutations in XPD(ERCC2) on pregnancy and prenatal development in
      mothers of patients with trichothiodystrophy or xeroderma pigmentosum.
AB  - The XPD(ERCC2) gene encodes a DNA helicase involved in DNA repair and
      transcription. Patients with mutations in XPD may have different autosomal
      recessive phenotypes including trichothiodystrophy (TTD) or xeroderma pigmentosum
      (XP). TTD patients have sulfur-deficient, brittle hair, short stature and
      developmental delay. In contrast, XP patients have freckle-like pigmentation and
      a greatly increased risk of sun-induced skin cancers. Mothers of TTD patients
      have been reported to have a high frequency of pregnancy and neonatal
      complications. We performed a molecular epidemiological study of 15 mothers of 17
      TTD patients and 13 mothers of 17 XP patients, all with XPD mutations. We found
      that 94% (16/17) of the TTD pregnancies had pre-term delivery, pre-eclampsia,
      hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, prematurity
      or low birth weight. None of the 17 XP pregnancies had these complications
      (P<0.001). As mutations in XPD may have differential effects on DNA repair and
      transcription, these observations should provide insights into the role of XPD in
      human pregnancy and fetal development.

PMID- 22617343
TI  - Phenotypic spectrum and genotype-phenotype correlations of NRXN1 exon deletions.
AB  - Copy number variants (CNVs) and intragenic rearrangements of the NRXN1 (neurexin
      1) gene are associated with a wide spectrum of developmental and neuropsychiatric
      disorders, including intellectual disability, speech delay, autism spectrum
      disorders (ASDs), hypotonia and schizophrenia. We performed a detailed clinical
      and molecular characterization of 24 patients who underwent clinical microarray
      analysis and had intragenic deletions of NRXN1. Seventeen of these deletions
      involved exons of NRXN1, whereas seven deleted intronic sequences only. The
      patients with exonic deletions manifested developmental delay/intellectual
      disability (93%), infantile hypotonia (59%) and ASDs (56%). Congenital
      malformations and dysmorphic features appeared infrequently and inconsistently
      among this population of patients with NRXN1 deletions. The more C-terminal
      deletions, including those affecting the beta isoform of neurexin 1, manifested
      increased head size and a high frequency of seizure disorder (88%) when compared
      with N-terminal deletions of NRXN1.

PMID- 22617344
TI  - Clinical utility gene card for: Centronuclear and myotubular myopathies.

PMID- 22617345
TI  - Efficiency of trans-ethnic genome-wide meta-analysis and fine-mapping.
AB  - Genome-wide association studies have seen unprecedented success in identifying
      genetic loci that correlate with disease susceptibility and severity. Early
      phases of these studies have predominantly been performed in the Caucasian
      populations. The next phase in medical genetics is to extend the exploration
      across genetically diverse populations to leverage on larger sample sizes for
      locating smaller effects that may be present in most human populations. However,
      discoveries from these studies do not actually reveal the underlying functional
      changes to the human genome, but only point to broad regions stipulated by the
      extent of linkage disequilibrium (LD). Fine-mapping the functional variants can,
      however, be hampered by extensive LD, which can yield multiple perfect surrogates
      that are not distinguishable from the underlying causal variants, although
      several studies have illustrated the value of relying on multiple genetically
      diverse populations to narrow the candidate regions where the functional variants
      can be found in. Here, we explore the efficiency of trans-ethnic meta-analysis in
      discovering genetic association and in fine-mapping the causal variants by
      asking: are there any population diversity metrics that will be useful for: (i)
      identifying the populations or genomic regions where meta-analysis are likely to
      be more successful for discovering associations?; (ii) identifying the
      populations or loci to perform deep targeted sequencing for the purpose of fine
      mapping causal variants? Our results indicate that simple metrics like the F(ST)
      or the population specificity of haplotypes are useful in trans-ethnic meta
      analyses, while the degree of haplotype sharing and LD variation are informative
      of the efficiency in trans-ethnic fine-mapping.

PMID- 22617346
TI  - Haploinsufficiency of CELF4 at 18q12.2 is associated with developmental and
      behavioral disorders, seizures, eye manifestations, and obesity.
AB  - Only 20 patients with deletions of 18q12.2 have been reported in the literature
      and the associated phenotype includes borderline intellectual disability,
      behavioral problems, seizures, obesity, and eye manifestations. Here, we report a
      male patient with a de novo translocation involving chromosomes 12 and 18, with
      borderline IQ, developmental and behavioral disorders, myopia, obesity, and
      febrile seizures in childhood. We characterized the rearrangement with Affymetrix
      SNP 6.0 Array analysis and next-generation mate pair sequencing and found
      truncation of CELF4 at 18q12.2. This second report of a patient with a
      neurodevelopmental phenotype and a translocation involving CELF4 supports that
      CELF4 is responsible for the phenotype associated with deletion of 18q12.2. Our
      study illustrates the utility of high-resolution genome-wide techniques in
      identifying neurodevelopmental and neurobehavioral genes, and it adds to the
      growing evidence, including a transgenic mouse model, that CELF4 is important for
      human brain development.

PMID- 22617347
TI  - Copy number variation in patients with cervical artery dissection.
AB  - Cervical artery dissection (CeAD) occurs in healthy young individuals and often
      entails ischemic stroke. Skin biopsies from most CeAD-patients show minor
      connective tissue alterations. We search for rare genetic deletions and
      duplication that may predispose to CeAD. Forty-nine non-traumatic CeAD-patients
      with electron microscopic (EM) alterations of their dermal connective tissue (EM+
      patients) and 21 patients with normal connective tissue in skin biopsies (EM-
      patients) were analyzed. Affymetrix 6.0 microarrays (Affymetrix) from all
      patients were screened for copy number variants (CNVs). CNVs absent from 403
      control subjects and from 2402 published disease-free individuals were considered
      as CeAD-associated. The genetic content of undentified CNVs was analyzed by means
      of the Gene Ontology (GO) Term Mapper to detect associations with biological
      processes. In 49 EM+ patients we identified 13 CeAD-associated CNVs harboring 83
      protein-coding genes. In 21 EM- patients we found five CeAD-associated CNVs
      containing only nine genes (comparison of CNV gene density between the groups:
      Mann-Whitney P=0.039). Patients' CNVs were enriched for genes involved in
      extracellular matrix organization (COL5A2, COL3A1, SNTA1, P=0.035), collagen
      fibril organization COL5A2, COL3A1, (P=0.0001) and possibly for genes involved in
      transforming growth factor beta (TGF)-beta receptor signaling pathway (COL3A1,
      DUPS22, P=0.068). We conclude that rare genetic variants may contribute to the
      pathogenesis of CeAD, in particular in patients with a microscopic connective
      tissue phenotype.

PMID- 22617348
TI  - Variants in the 3'UTR of SNCA do not affect miRNA-433 binding and alpha-synuclein
      expression.
AB  - Alpha-synuclein (SNCA) is a major risk gene for Parkinson's disease (PD) and
      increased SNCA gene dosage results in a parkinsonian syndrome in affected
      families. Regulatory regions relevant for SNCA expression include the 3'
      untranslated region (UTR), which among other regulatory elements contains several
      micro-RNA-binding sites. Interestingly, variants located in the 3' region of SNCA
      have been associated with PD in two genome-wide association studies. To test
      whether private mutations in this region contribute to PD, we sequenced the 3'UTR
      of SNCA in 1285 PD patients and 1120 age/sex-matched healthy controls. We found
      two rare variants, the one corresponding to the single nucleotide polymorphism
      rs145304567 and the novel variant c.*1004_1008delTTTTT. Although rs145304567
      affects the putative-binding site of microRNA (miRNA) -433, the allele
      distribution was similar in PD patients and controls, and the expression of SNCA
      mRNA was not related to the genotype. Furthermore, a regulatory effect of miRNA
      433 on SNCA expression levels was not detected.

PMID- 22617349
TI  - Apigenin decreases cell viability and telomerase activity in human leukemia cell
      lines.
AB  - Recent studies have shown that apigenin (4',5,7-trihydroxyflavone inhibits human
      malignant cancer cell growth through cell cycle arrest and apoptosis. However,
      the underlying relationship between apoptosis and telomerase activity in response
      to apigenin exposure is not well understood. In this study, we found that
      apigenin significantly induces direct cytotoxicity in human leukemia cells (U937,
      THP-1 and HL60) through activation of the caspase pathway. As we presumed,
      treatment with apigenin was found to increase the level of intracellular reactive
      oxygen species (ROS), whereas pretreatment with antioxidants, N-acetyl-cysteine
      (NAC) or glutathione (GSH), completely attenuated ROS generation. Surprisingly,
      these antioxidants did not promote recuperation from apigenin-induced cell death.
      We further showed that apigenin downregulates telomerase activity in caspase
      dependent apoptosis and observed that apigenin dosing results in downregulation
      of telomerase activity by suppression of c-Myc-mediated telomerase reverse
      transcriptase (hTERT) expression. In addition, treatment of apigenin-dosed cells
      with the two antioxidants did not restore telomerase activity. Taken together,
      this data suggests that ROS is not essential for suppression of apigenin-mediated
      apoptosis associated with the activation of caspases and regulation of telomerase
      activity via suppression of hTERT. We conclude that apigenin has a direct
      cytotoxic effect and the loss of telomerase activity in leukemia cells.

PMID- 22617350
TI  - Phloroglucinol: antioxidant properties and effects on cellular oxidative markers
      in human HepG2 cell line.
AB  - Phloroglucinol is an ubiquitous secondary metabolite encountered in a free state
      or polymerised as phlorotannins in brown macroalgae, and present in higher
      plants. FRAP and TEAC assays measured the antioxidant properties of
      phloroglucinol in non-biological conditions. Additionally, the biological effects
      of phloroglucinol (4-400 MUM) were scrutinised using cellular oxidative stress
      markers, such as the generation of ROS, antioxidant defences (concentration of
      GSH and activities of GPx, GR and GST), and levels of MDA as a marker for lipid
      peroxidation. The direct effect was assessed immediately after an incubation
      period, whereas for the protective effect, the incubation period was followed by
      3-h treatment with the pro-oxidant t-BOOH. The results indicated that despite
      having a higher radical scavenging capacity than Trolox after 30 min,
      phloroglucinol was not a suitable antioxidant standard for phlorotannins.
      Regarding the biological effects, phloroglucinol had no impact on cell viability,
      reduced levels of ROS and increased antioxidant defences in the direct treatment
      for most concentrations. The results of the protective effect were mitigated as
      phloroglucinol failed to protect from ROS generation but evoked a significant
      recovery of the stress-altered cellular antioxidant defences to restful
      conditions. Additionally, MDA levels were greatly reduced, preventing a radical
      chain oxidation.

PMID- 22617351
TI  - Membrane filtration of Sudan orange G on a cellulose acetate membrane filter for
      separation-preconcentration and spectrophotometric determination in water, chili
      powder, chili sauce and tomato sauce samples.
AB  - A simple membrane filtration procedure for separation-enrichment of Sudan orange
      G is presented. The method is based on the adsorption of Sudan orange G on a
      cellulose acetate filter and its elution from the membrane with 10 mL of ethanol.
      Sudan orange G in the eluent was determined by UV-visible spectrophotometry at
      388 nm. The effect of analytical conditions, including pH, flow rates and eluent,
      sample volume, type of membrane for quantitative preconcentration and separation
      of Sudan orange G were examined. The influences of matrix components on Sudan
      orange G recoveries were studied. The preconcentration factor was 125. The
      detection limit was 4.9 MUg L(-1). The relative standard deviation was 4.3%. The
      presented procedure was applied to chili powder, chili sauce, tomato sauce,
      powdered beverage and water samples.

PMID- 22617352
TI  - Determination of acrylamide level in commercial baby foods and an assessment of
      infant dietary exposure.
AB  - Acrylamide is a monomer that can form in heated starchy food as a result of
      Maillard reaction. The adverse effects of acrylamide in humans are neurotoxicity
      and carcinogenicity. Aim of our study was to determine acrylamide levels in the
      main categories of commercially made Polish baby food products and to assess the
      dietary acrylamide exposure of infants aged 6-12 months. Acrylamide content in
      baby food products was analysed by GCQ-MS/MS and LC-MS/MS methods. The exposure
      assessment was carried out using analytical data and recommended daily
      consumption of food in individual months of infant life. The infant exposure was
      estimated at three levels: minimum, average and maximum. The mean content of
      acrylamide in the baby foods ranged from 2 to 516 MUg/kg depending on the food
      product. The exposure of infants aged 6-12 months of life was estimated at the
      minimum level in the range from 0.41 to 0.62 MUg/kg b.w./day, and at the average
      level - from 2.10 to 4.32 MUg/kg b.w./day. For the worst case scenario the
      exposure ranged from 7.47 to 12.35 MUg/kg b.w./day and was more than a dozen
      times and even several dozen times higher than the exposure estimated for the
      total Polish population.

PMID- 22617353
TI  - Acetylcholinesterase inhibition, antioxidant activity and toxicity of Peumus
      boldus water extracts on HeLa and Caco-2 cell lines.
AB  - This work aimed to study the inhibition on acetylcholinesterase activity (AChE),
      the antioxidant activity and the toxicity towards Caco-2 and HeLa cells of
      aqueous extracts of Peumus Boldus. An IC(50) value of 0.93 mg/mL, for AChE
      inhibition, and EC(50) of 18.7 MUg/mL, for the antioxidant activity, was
      determined. This activity can be attributed to glycosylated flavonoid derivatives
      detected, which were the main compounds, although boldine and other aporphine
      derivatives were also present. No changes in the chemical composition or the
      biochemical activities were found after gastrointestinal digestion. Toxicity of
      P. boldus decoction gave an IC(50) value 0.66 mg/mL for HeLa cells, which caused
      significant changes in the cell proteome profile.

PMID- 22617354
TI  - Platycodin D, a triterpenoid sapoinin from Platycodon grandiflorum, ameliorates
      cisplatin-induced nephrotoxicity in mice.
AB  - Platycodin D (PD) is well known as a potent triterpenoid saponin having various
      pharmacological activities isolated from the root of Platycodon grandiflorum
      (Jacq.) A. DC. (Campanulaceae). We aimed to evaluate protective effect of PD on
      cisplatin (CDDP)-induced nephrotoxicity. Male ICR mice were allocated into five
      groups as follows: Negative control, CDDP alone and CDDP with PD (0.1, 1 and 5
      mg/kg) treated group. PD was given for three consecutive days before CDDP
      injection. Increased blood urea nitrogen (BUN) and creatinine (CRE) levels in
      CDDP alone treated mice were decreased to normal range by pretreatment with PD.
      It also decreased nitric oxide (NO) and lipid peroxidation with increased
      antioxidant enzymes such as glutathione (GSH), glutathione peroxidase (GPx) and
      superoxide dismutase (SOD) in PD pretreated mice. In histopathological
      examination, pretreatment with PD showed ameliorated renal injury such as
      intraluminal cast formation and epithelial desquamation. Furthermore, over
      expression of nuclear factor-kappa B p65 and apoptotic cells were suppressed by
      PD pretreatment. Taken together, PD pretreatment might be beneficial to CDDP
      induced nephrotoxicity.

PMID- 22617355
TI  - Withdrawal-associated increases and decreases in functional neural connectivity
      associated with altered emotional regulation in alcoholism.
AB  - Alcoholic patients who have undergone multiple detoxifications/relapses show
      altered processing of emotional signals. We performed functional magnetic
      resonance imaging during performance of implicit and explicit versions of a task
      in which subjects were presented with morphs of fearful facial emotional
      expressions. Participants were abstaining, multiply detoxified (MDTx; n=12) or
      singly detoxified patients (SDTx; n=17), and social drinker controls (n=31).
      Alcoholic patients were less able than controls to recognize fearful expressions,
      and showed lower activation in prefrontal areas, including orbitofrontal cortex
      and insula, which mediate emotional processing. The decrease in activation was
      greater in MDTx patients who also showed decreased connectivity between insula
      and prefrontal areas, and between amygdala and globus pallidus. In the explicit
      condition, the strength of connectivity between insula and areas involved in
      regulation of emotion (inferior frontal cortex and frontal pole) was negatively
      correlated with both the number of detoxifications and dependency (measured by
      the severity of alcohol dependency (SADQ) and control over drinking score
      (Impaired Control questionnaire, ICQ)). In contrast, increased connectivity was
      found between insula and the colliculus neuronal cluster, and between amygdala
      and stria terminalis bed nucleus. In the implicit condition, number of
      detoxifications and ICQ score correlated positively with connectivity between
      amygdala and prefrontal cortical areas involved in attentional and executive
      processes. Repeated episodes of detoxification from alcohol are associated with
      altered function both in fear perception pathways and in cortical modulation of
      emotions. Such changes may confer increased sensitivity to emotional stress and
      impaired social competence, contributing to relapse.

PMID- 22617356
TI  - Yohimbine depresses excitatory transmission in BNST and impairs extinction of
      cocaine place preference through orexin-dependent, norepinephrine-independent
      processes.
AB  - The alpha2 adrenergic receptor (alpha(2)-AR) antagonist yohimbine is a widely
      used tool for the study of anxiogenesis and stress-induced drug-seeking behavior.
      We previously demonstrated that yohimbine paradoxically depresses excitatory
      transmission in the bed nucleus of the stria terminalis (BNST), a region critical
      to the integration of stress and reward pathways, and produces an impairment of
      extinction of cocaine-conditioned place preference (cocaine-CPP) independent of
      alpha(2)-AR signaling. Recent studies show yohimbine-induced drug-seeking
      behavior is attenuated by orexin receptor 1 (OX(1)R) antagonists. Moreover,
      yohimbine-induced cocaine-seeking behavior is BNST-dependent. Here, we
      investigated yohimbine-orexin interactions. Our results demonstrate yohimbine
      induced depression of excitatory transmission in the BNST is unaffected by alpha1
      AR and corticotropin-releasing factor receptor-1 (CRFR(1)) antagonists, but is
      (1) blocked by OxR antagonists and (2) absent in brain slices from orexin
      knockout mice. Although the actions of yohimbine were not mimicked by the
      norepinephrine transporter blocker reboxetine, they were by exogenously applied
      orexin A. We find that, as with yohimbine, orexin A depression of excitatory
      transmission in BNST is OX(1)R-dependent. Finally, we find these ex vivo effects
      are paralleled in vivo, as yohimbine-induced impairment of cocaine-CPP extinction
      is blocked by a systemically administered OX(1)R antagonist. These data highlight
      a new mechanism for orexin on excitatory anxiety circuits and demonstrate that
      some of the actions of yohimbine may be directly dependent upon orexin signaling
      and independent of norepinephrine and CRF in the BNST.

PMID- 22617359
TI  - Celiac disease and giardiasis:  a case report.
AB  - When investigating a patient with suspected celiac disease (CD), several other
      conditions must be considered, including potential infection with Giardia
      lamblia. Although giardiasis is rare, its histopathological and serological
      picture may resemble that of CD. We report the case of a young man with diabetes
      mellitus and a family history of CD referred to our hospital because of diarrhoea
      and weight loss. Investigation showed, among other factors, partial villous
      atrophy in duodenal biopsies and elevated immunoglobulin A antitissue
      transglutaminase antibodies. The patient was diagnosed with CD and recommended a
      gluten-free diet. At the same time, faecal tests were conducted, indicating the
      presence of G. lamblia. The patient was treated and improved, even after
      discontinuing the gluten-free diet. Subsequent follow-up after 6 months showed
      total regression of mucosal histopathology and a normal antitissue
      transglutaminase antibodies level.

PMID- 22617357
TI  - Amygdala subregions tied to SSRI and placebo response in patients with social
      anxiety disorder.
AB  - The amygdala is a key structure in the pathophysiology of anxiety disorders, and
      a putative target for anxiolytic treatments. Selective serotonin reuptake
      inhibitors (SSRIs) and placebo seem to induce anxiolytic effects by attenuating
      amygdala responsiveness. However, conflicting amygdala findings have also been
      reported. Moreover, the neural profile of responders and nonresponders is
      insufficiently characterized and it remains unknown whether SSRIs and placebo
      engage common or distinct amygdala subregions or different modulatory cortical
      areas. We examined similarities and differences in the neural response to SSRIs
      and placebo in patients with social anxiety disorder (SAD). Positron emission
      tomography (PET) with oxygen-15-labeled water was used to assess regional
      cerebral blood flow (rCBF) in 72 patients with SAD during an anxiogenic public
      speaking task, before and after 6-8 weeks of treatment under double-blind
      conditions. Response rate was determined by the Clinical Global Impression
      Improvement scale. Conjunction analysis revealed a common rCBF-attenuation from
      pre- to post-treatment in responders to SSRIs and placebo in the left
      basomedial/basolateral and right ventrolateral amygdala. This rCBF pattern
      correlated with behavioral measures of reduced anxiety and differentiated
      responders from nonresponders. However, nonanxiolytic treatment effects were also
      observed in the amygdala. All subgroups, including nonresponders, showed
      deactivation of the left lateral part of the amygdala. No rCBF differences were
      found between SSRI responders and placebo responders. This study provides new
      insights into the brain dynamics underlying anxiety relief by demonstrating
      common amygdala targets for pharmacologically and psychologically induced anxiety
      reduction, and by showing that the amygdala is functionally heterogeneous in
      anxiolysis.

PMID- 22617358
TI  - Previous exposure to nicotine enhances the incentive motivational effects of
      amphetamine via nicotine-associated contextual stimuli.
AB  - The effect of nicotine exposure on the subsequent self-administration of
      amphetamine, extinction of this behavior, and amphetamine-induced reinstatement
      of drug seeking was assessed with particular attention to the contribution of
      contextual stimuli paired or unpaired with nicotine during exposure. Rats were
      exposed to five injections, one injection every third day, of either saline or
      nicotine (0.4 mg/kg, IP, base) in three experiments. In one, exposure injections
      were administered in the home cage. In another, they were administered in the
      self-administration chambers with the levers retracted. In a third, nicotine was
      administered either explicitly paired or unpaired with the self-administration
      chambers using a discrimination learning procedure. Starting 13-15 days later,
      rats were trained to self-administer amphetamine (100 MUg/kg/infusion, IV),
      tested under a progressive ratio (PR) schedule for 6 days, subjected to up to 20
      days of extinction training, and were then tested for reinstatement by non
      contingent injections of amphetamine (0, 0.2, 0.4, and 0.75 mg/kg, IP). Nicotine
      enhanced the self-administration of amphetamine under the PR schedule and
      amphetamine-induced reinstatement but only when rats were tested in the chamber
      in which they were previously exposed to nicotine. These effects were not
      observed in rats exposed to nicotine in the home cage or in rats exposed to
      nicotine explicitly unpaired with the self-administration chambers. Exposure to
      nicotine also rendered rats resistant to extinction when amphetamine was withheld
      but this effect was observed regardless of nicotine exposure context, suggesting
      a separate consequence of drug exposure. Together, these results show that
      previous exposure to nicotine can enhance the incentive motivational effects of
      other psychostimulants like amphetamine and indicate a critical role for nicotine
      associated contextual stimuli in the mediation of this effect. These findings
      have important implications for the treatment of addictions in humans.

PMID- 22617360
TI  - Manifestations of juvenile polyposis syndrome in SMAD4 mutation carriers of a
      kindred.
AB  - The autosomal dominantly inherited juvenile polyposis syndrome (JPS) leads to the
      development of multiple hamartomatous polyps in the gastrointestinal tract and is
      a precancerous condition. In a large family with a newly identified SMAD4
      mutation (c.543delC), we describe the clinical manifestations of JPS. Nine
      affected SMAD4 mutation-positive family members were screened and treated for
      manifestations of JPS. Two family members were symptomatic at the time of
      diagnosis; seven were asymptomatic - independent of the severity of the
      manifestation. Each mutation carrier presented with colonic juvenile polyps,
      seven out of nine with additional gastric manifestations. One asymptomatic
      patient had early gastric cancer; another patient had a villous adenoma with high
      grade intraepithelial neoplasia in the colon. Three patients had biliary lesions
      including a bile duct hamartoma in one and gallbladder polyps in two. Three
      patients had gastrointestinal vascular malformations. All mutation carriers were
      affected by JPS. Interestingly, the manifestations and their severity differed
      considerably between the patients, suggesting secondary factors influencing JPS
      manifestations such as Helicobacter pylori infection.

PMID- 22617361
TI  - Cyclic vomiting syndrome in 28 patients:  demographics, features and outcomes.
AB  - INTRODUCTION: Cyclic vomiting syndrome (CVS) is a condition characterized by
      recurrent, stereotyped, attacks of intense nausea and intractable vomiting with
      no identifiable cause. The diagnosis is made according to the Rome III criteria;
      however, the condition remains a heterogenous group of symptoms and few studies
      have analysed patient-reported features in detail. Tricyclic antidepressants may
      benefit some patients, but there are no data on the long-term outcomes of this
      condition. METHODS: This is a retrospective cohort study of all patients treated
      at two London teaching hospitals between 1994 and 2011. Information was obtained
      by means of inpatient case notes, clinic letters and telephone interviews using a
      standardized questionnaire. RESULTS: Twenty-eight patients were identified, 17
      with adult-onset CVS and 11 with childhood-onset CVS. In the adult-onset CVS
      cohort, the average age of onset was 30 years; the prevalence of headache was
      57.1% and anxiety/depression 21.7%. Vomiting attacks occurred on average 10 times
      a year with a mean duration of 55.3 h. In the childhood-onset CVS cohort, the
      average age of onset was 5 years and the prevalence of headaches was 44.4%.
      Vomiting attacks occurred on average 25.5 times a year with a mean duration of
      54.5 h. During acute attacks, patients rated morphine-based medications as the
      most efficacious. Overall, 65.4% of our patients were not treated with long-term
      prophylactic medications and, of these, 42.1% felt that their symptoms had
      improved and 26.3% reported complete resolution. CONCLUSION: CVS is a
      debilitating illness with frequent attacks of prolonged duration. There is a high
      association with anxiety/depression as well as headaches. Antimigraine
      medication, beta-blockers and antiepileptic treatment may be successful at
      attenuating attacks; however, in this long-term study, the prognosis of patients
      not treated with these medications was also good. Overall, 61.9% of patients
      showed a gradual improvement in symptoms and 23.8% had complete resolution after
      a mean of 7 years.

PMID- 22617362
TI  - Clinical course of drug-induced collagenous colitis and histological changes
      after drug withdrawal in a Japanese case series.
AB  - Although the incidence of drug-induced collagenous colitis has been increasing,
      details of its clinical course and histological changes after withdrawal of the
      suspected causative drugs remain unclear. To shed light on this issue, we studied
      15 patients with collagenous colitis diagnosed between 1999 and 2011 in our
      hospital. Clinical cure was achieved in 14 patients after withdrawal of the
      suspected causative drugs and in one patient after the administration of
      prednisolone. Six patients underwent a second colorectal endoscopic examination
      after clinical cure, and the histological features were compared with those in
      patients during the clinically active phase. Four of these six patients showed
      disappearance of the collagen band and a decrease in inflammatory cells, but the
      collagen band remained in the other two despite a decrease in inflammatory cells.
      Cell proliferation as shown by Ki-67 immunostaining was restored to normal,
      irrespective of whether the collagen band was retained. The surface-absorptive
      epithelia became mature in all patients. Histological improvement in collagenous
      colitis is believed to involve normalization of cell proliferation and maturation
      of the absorptive epithelium, and not necessarily disappearance of the collagen
      band.

PMID- 22617363
TI  - A comparison of surgery versus transcatheter angiographic embolization in the
      treatment of nonvariceal upper gastrointestinal bleeding uncontrolled by
      endoscopy.
AB  - BACKGROUND: Patients with recurrent nonvariceal upper gastrointestinal bleeding
      who have failed endoscopic therapy pose a challenge. Percutaneous transcatheter
      angiographic embolization (TAE) is an alternative to surgery but remains
      controversial. This study compares the treatment outcomes in patients with
      recurrent nonvariceal upper gastrointestinal bleeding. METHODS: A retrospective
      single-centre study of consecutive patients who underwent TAE (January 2007
      December 2010) compared with patients treated surgically (January 2004-December
      2010) was conducted. Patient demographics, comorbidities, rebleeding rates,
      length of stay and mortality were compared. RESULTS: Thirty [23 men; age (SD)
      66.5+/-15.6 years] and 63 [41 men; age (SD) 68.2+/-15.0 years, NS] patients
      underwent TAE and surgery after a mean (SD) of 1.7+/-1.0 and 2.1+/-1.1 (NS)
      gastroscopies, respectively, for gastric ulcers (n=28), duodenal ulcers (n=53),
      small-bowel diverticuli (n=7), jejunal ulcer (n=1) and gastric Dieulafoy's
      lesions (n=2). Ten (33.3%) and 44 (69.8%) patients who underwent TAE and surgery,
      respectively, had an American Society of Anesthesiologists status of at least 2
      (P=0.001). Higher rebleeding rates were observed after TAE compared with surgery
      [n=14 (46.7%) vs. 8 (12.7%), P=0.001]; however, there were no significant
      differences in 30-day mortality (16.7 vs. 19.0%, NS), complication rates (46.7
      vs. 60.3%, NS) and length of stay (45.1+/-9.8 vs. 25.5+/-18.1 days, P=0.06).
      Twenty-four out of 30 patients (80%) who underwent TAE achieved haemostasis after
      a median (SD) of 2.0 (1.2) TAE procedures. Rebleeding occurred in five out of
      seven patients (71%) who underwent TAE for small-bowel diverticular bleeding.
      CONCLUSION: TAE averted the need for surgery in high-risk patients. Its role in
      low surgical risk patients or patients with small-bowel diverticular bleeding
      requires further study.

PMID- 22617364
TI  - Visceral fat predominance is associated with erosive esophagitis in Japanese men
      with metabolic syndrome.
AB  - BACKGROUND AND AIM: Although visceral fat is strongly associated with metabolic
      syndrome (MS), the association between erosive esophagitis (EE) and visceral and
      subcutaneous fat types in individuals with MS has remained unclear. In this
      study, we divided individuals with MS into those with visceral and subcutaneous
      fat types, and determined the differences in the presence of EE between the types
      of MS in Japanese men. METHODS: The participants were 265 men with MS who
      underwent a medical checkup including upper gastrointestinal endoscopy and
      abdominal ultrasonography. We made a distinction between visceral and
      subcutaneous fat types of MS by ultrasonography, and examined for the presence of
      EE, and the correlation between EE and other data. RESULTS: Total cholesterol,
      low-density lipoprotein cholesterol, alanine aminotransferase, and the frequency
      of EE were significantly higher in visceral fat-type MS than in subcutaneous fat
      type MS. On logistic regression analysis with EE as a dependent variable and the
      significant background factors as the independent variables, visceral fat-type MS
      and hiatal hernia were significant predictors of an increased prevalence of EE
      (odds ratios=3.808 and 8.599; 95% confidence intervals=1.710-8.479 and 4.206
      17.58; P<0.005 and <0.001, respectively). CONCLUSION: Japanese men with visceral
      fat-type MS are more likely to have dyslipidemia and EE than those with
      subcutaneous fat-type MS. Visceral fat-type MS is one of the most significant
      predictors of an increased prevalence of EE in Japanese men with MS.

PMID- 22617365
TI  - Transcatheter arterial embolization for iatrogenic hemobilia is a safe and
      effective procedure:  case series and review of the literature.
AB  - OBJECTIVE: Hemobilia is an uncommon cause of gastrointestinal bleeding. The
      etiology is diverse, but most often, it is iatrogenic. The present study aims to
      reassess the clinical picture and the treatment of choice. METHODS: We describe a
      case series from a single center of patients who presented with nontraumatic
      iatrogenic hemobilia. RESULTS: Over a period of 8 years, hemobilia occurred in 12
      patients: following liver biopsy in six patients and after endoscopic biliary
      interventions in four patients, with a respective prevalence of 0.1 and 0.04%.
      The clinical presentation was characterized by an upper gastrointestinal bleeding
      (n=11) and/or biochemical signs of sudden biliary obstruction (n=9). The onset of
      the symptoms occurred after a median of 6 days (range: 1-23). Ultrasound and
      computed tomography scan missed the diagnosis in, respectively, 4/5 and 2/5 of
      patients. On arteriography, pseudoaneurysm (6/12) was the most common finding.
      Transcatheter arterial embolization controlled the bleeding in all cases (12/12)
      without major complications. CONCLUSION: The delay between the intervention and
      the clinical presentation and the fact that imaging studies may fail to diagnose
      hemobilia may mislead the physician. Transcatheter arterial embolization is the
      treatment of choice for hemobilia. It has proven to be effective and safe and it
      offers a long-term definitive cure.

PMID- 22617366
TI  - A comparison of a short nurse-based and a long multidisciplinary version of
      structured patient education in irritable bowel syndrome.
AB  - OBJECTIVE: Structured multidisciplinary patient group education has positive
      effects on symptoms, health-related quality of life, and disease-related
      knowledge in patients with irritable bowel syndrome (IBS), but few studies
      comparing different forms of educational interventions are available. Our aim was
      to compare the effects of long multidisciplinary group education with a short
      nurse-based group education with regard to symptoms, knowledge, quality of life,
      and satisfaction with the intervention in IBS patients. METHODS: Patients with
      IBS according to the Rome II criteria were randomized to either short nurse-based
      or a long multidisciplinary-based education. The effects were evaluated by self
      administered questionnaires at 3, 6, and 12 months after baseline, and compared
      between the groups. RESULTS: No differences in effects were detected in the
      between-group comparisons at any of the follow-up assessments. However, positive
      effects on symptoms, knowledge, quality of life, and satisfaction with the
      intervention were found in both the short and the long version. CONCLUSION: A
      short, nurse-based educational intervention seems to be as efficacious as a
      longer multidisciplinary version. In both groups, positive effects on patients'
      well-being were found to a similar extent. This is an important finding that,
      from a cost-effective perspective, could contribute toward an optimized
      management of patients with IBS.

PMID- 22617367
TI  - The burden of viral hepatitis C in Europe:  a propensity analysis of patient
      outcomes.
AB  - OBJECTIVE: Hepatitis C virus (HCV) affects 170 million patients worldwide and is
      the leading cause of liver cirrhosis and hepatocellular carcinoma. The aim of the
      current study is to examine the burden of HCV in the European Union (EU) from a
      patient perspective. METHODS: Using data from the 2010 EU National Health and
      Wellness Survey, patients who reported a diagnosis of HCV (n=332) were compared
      with a propensity-score-matched non-HCV control group (n=332) on measures of
      quality of life (using the SF-12v2), work productivity, and healthcare resource
      utilization in the past 6 months. All analyses applied sampling weights to
      project to the respective country populations. RESULTS: Projected prevalence
      estimates of HCV were 0.59% in France, 0.44% in Germany, 1.42% in Italy, 0.82% in
      Spain, and 0.35% in the UK. HCV patients reported significantly lower levels of
      emotional role limitations (means=66.4 vs. 70.6, P=0.040), physical functioning
      (means=63.8 vs. 71.9, P=0.001), general health (means=48.3 vs. 54.4, P=0.004),
      bodily pain (means=64.3 vs. 70.8, P=0.002), and physical component summary scores
      (means=42.9 vs. 45.3, P=0.002) than the matched controls. Patients with HCV also
      reported significantly higher levels of presenteeism (means=27.1 vs. 21.0%,
      P=0.044) and a greater number of physician visits in the past 6 months (means=9.9
      vs. 6.7, P<0.001). CONCLUSION: Using a population-based survey methodology and a
      propensity-score matching analysis, these results add to the literature by
      documenting the significant effect that HCV has on a variety of both humanistic
      and economic outcomes in the EU.

PMID- 22617369
TI  - [Paediatric oncology in Hungary].
AB  - The significance of paediatric oncology is increasing due to its increasing
      incidence and its leading role among the causes of mortality in children. The
      epidemiology, prophylaxis and therapy of paediatric malignancies in Hungary are
      discussed surveying the results and the most important tasks in the future.

PMID- 22617368
TI  - Methodological innovations expand the safety pharmacology horizon.
AB  - Almost uniquely in pharmacology, drug safety assessment is driven by the need for
      elaboration and validation of methods for detecting drug actions. This is the 9th
      consecutive year that the Journal of Pharmacological and Toxicological Methods
      (JPTM) has published themed issues arising from the annual meeting of the Safety
      Pharmacology Society (SPS). The SPS is now past its 10th year as a distinct (from
      pharmacology to toxicology) discipline that integrates safety pharmacologists
      from industry with those in academia and the various global regulatory
      authorities. The themes of the 2011 meeting were (i) the bridging of safety
      assessment of a new chemical entity (NCE) between all the parties involved, (ii)
      applied technologies and (iii) translation. This issue of JPTM reflects these
      themes. The content is informed by the regulatory guidance documents (S7A and
      S7B) that apply prior to first in human (FIH) studies, which emphasize the
      importance of seeking model validation. The manuscripts encompass a broad
      spectrum of safety pharmacology topics including application of state-of-the-art
      techniques for study conduct and data processing and evaluation. This includes
      some exciting novel integrated core battery study designs, refinements in
      hemodynamic assessment, arrhythmia analysis algorithms, and additionally an
      overview of safety immunopharmacology, and a brief survey discussing similarities
      and differences in business models that pharmaceutical companies employ in safety
      pharmacology, together with SPS recommendations on 'best practice' for the
      conduct of a non-clinical cardiovascular assessment of a NCE.

PMID- 22617370
TI  - [Flexor tendon surgery: advances in the field of hand surgery].
AB  - Reconstruction of the flexor tendon injuries is one of the most difficult
      problems in hand surgery, because the postoperative end-results are often
      unfavorable. The author discusses the history of the flexor tendon surgery, and
      then he describes the development of the knowledge regarding the anatomy, the
      blood supply and the tendon healing of the flexor tendons from the beginning
      until now. After that he describes the development in suture materials, suture
      techniques, primary and secondary tendon reconstruction operations, postoperative
      treatment and rehabilitation programmes. The author describes what kind of
      progress to be expected in this field in the near future, and then he expresses
      his viewpoint about the development in the international and national hand
      surgical societies. He encloses a detailed list of literature for those who are
      interested in the field.

PMID- 22617371
TI  - [Sociology of health, social ecology and media democracy].
AB  - The correlation of the sociology of health, social ecology and media democracy is
      demonstrated in the study. In societies of today, the role of the media is
      unquestionable in disseminating information relating to health and the
      environment. According to Paragraph (1) of Article XXI of the Hungarian
      Constitution of 2011, everyone has the right to a healthy environment. An
      environmentalist media democracy may forward environmental justice, environmental
      education, and environmentalist economy, etc. All these are required in order to
      establish a society where the healthy environment is an objective value.

PMID- 22617372
TI  - [Endoscopic submucosal dissection in our practice -- new possibilities in the
      endoscopic treatment of neoplastic changes in the alimentary canal].
AB  - Endoscopic submucosal dissection is a promising new endoscopic technique for en
      block resection of early, superficial, flat, and laterally spreading
      gastrointestinal neoplasms. The primary aims of this prospective study were to
      summarize the first Hungarian experience with endoscopic submucosal dissection,
      and to compare the experimental in vivo procedures in pigs with the human
      application of this technique in two academic centers. METHODS: The ex vivo
      Erlangen pig model was used until initial competence was achieved. Thereafter 15
      endoscopic submucosal dissection procedures were performed in up to 5 sessions in
      living pigs under general anesthesia. After submucosal injection with saline
      Fujinone ball tip, a Flush knife was used with a transparent hood for
      circumferential incision and submucosal dissection. The following variables were
      analyzed: specimen size, complete and en bloc resection rate, total duration of
      the procedure, and complications. Furthermore, between 2009 and 2012, 14
      endoscopic submucosal dissections were carried out in humans; 1 duodenal, 3
      gastric and 10 colorectal interventions were performed due to large laterally
      spreading intramucosal neoplasms. The specimen size, en bloc resection rate,
      total duration of the procedure and complications were next analyzed. RESULTS:
      87% complete resection rate, 29.4 +/- 19.5 cm2 specimen size and 136.2 +/- 26.8
      min of procedure duration were achieved in the live pig models. Nontransmural
      damages of the muscular layer occurred in 3/15 (20%) cases which were
      successfully closed with hemoclips, except in one pig that died due to fatal
      esophageal perforation. All bleedings were easily managed with hot biopsy forceps
      coagulation and hemoclips without hemodynamic instability. In humans, endoscopic
      submucosal dissection was accomplished with an 11/14 (79%) en block resection
      rate, with average resected specimen size of 11.56 +/- 4.9 cm2 and with 157 +/-
      55 min of operating time. Two cases of bleeding and 2 cases of perforation
      occurred (14%), all of which were managed endoscopically. After 1.5 year of
      average follow up, local recurrence occurred in one case only. In addition, due
      to the 3 incomplete resections and unsuccessful endoscopic submucosal dissection,
      surgical intervention was required in 4 cases altogether. CONCLUSIONS: This study
      demonstrates the first Hungarian experience with endoscopic submucosal
      dissection. Training in live pig models could help endoscopists to overcome the
      learning curve and minimize the risk of complications before starting the
      procedure in humans. Reduction in the resection time and low risk of
      complications, especially bleeding, could be achieved by the application of a
      flush knife.

PMID- 22617375
TI  - Crossmodal interactions and multisensory integration in the perception of audio
      visual motion -- a free-field study.
AB  - Motion perception can be altered by information received through multiple senses.
      So far, the interplay between the visual and the auditory modality in peripheral
      motion perception is scarcely described. The present free-field study
      investigated audio-visual motion perception for different azimuthal trajectories
      in space. To disentangle effects related to crossmodal interactions (the
      influence of one modality on signal processing in another modality) and
      multisensory integration (binding of bimodal streams), we manipulated the
      subjects' attention in two experiments on a single set of moving audio-visual
      stimuli. Acoustic and visual signals were either congruent or spatially and
      temporally disparate at motion offset. (i) Crossmodal interactions were studied
      in a selective attention task. Subjects were instructed to attend to either the
      acoustic or the visual stream and to indicate the perceived final position of
      motion. (ii) Multisensory integration was studied in a divided attention task in
      which subjects were asked to report whether they perceived unified or separated
      audio-visual motion offsets. The results indicate that crossmodal interactions in
      motion perception do not depend on the integration of the audio-visual stream.
      Furthermore, in the crossmodal task, both visual and auditory motion perception
      were susceptible to modulation by irrelevant streams, provided that temporal
      disparities did not exceed a critical range. Concurrent visual streams modulated
      auditory motion perception in the central field, whereas concurrent acoustic
      streams attracted visual motion information in the periphery. Differential
      abilities between the visual and auditory system when attempting to accurately
      track positional information along different trajectories account for the
      observed biasing effects.

PMID- 22617376
TI  - Microglia activation along the corticospinal tract following traumatic brain
      injury in the rat: a neuroanatomical study.
AB  - Traumatic injury to the brain often manifests itself symptomatically and
      structurally long after the traumatic event. The cellular basis of this complex
      response is not completely understood. However, we hypothesized that microglia
      might contribute to the brain-wide process. To test this hypothesis, we employed
      optical and electron microscopy to study the microglia in rat brains up to 2
      months after digitally controlled cortical impact (CCI) to produce traumatic
      brain injury (TBI). We also used antibodies against ED-1 and Iba-1, respectively,
      as markers for activated and resting microglia. ED-1 positive microglial cells
      are observed accompanying the entire corticospinal tract (CST) on the injured
      side, but not the control, contralateral side of the brain at 2 months. In this
      case, ED-1 and Iba-1 were observed to co-localize uniquely on the injured side of
      the brain. At earlier times following CCI, ultrastructural studies reveal that
      microglial cells have very irregular shapes and have many processes that
      intermingle with degenerating nerve axons of the CST in the hindbrain pyramids.
      These cells appear to be engulfing degenerating myelinated axons. The debris
      within the cells is converted to lipofuscin, the antigen for the ED-1 antibody,
      and remains in the cell cytoplasm throughout the life of the cell. We conclude,
      as hypothesized, that microglia are critical cellular components. Based on
      observed close association with myelin degeneration, interdigitating activated
      microglia may be contributing to damage control. Finally, based on the close
      neuroanatomical relationship between the lesioned corticospinal tract and the
      wide distribution of activated microglia, primary signals from CST neurons per
      se, may be directing microglial responses along the entire damaged rat neuroaxis.
      The role of persistent activation of microglia has not been determined.

PMID- 22617377
TI  - Anti-nociceptive and anti-inflammatory effects of Croton crassifolius ethanol
      extract.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Croton crassifolius has been used to treat snake
      bites, stomach ache, sternalgia, joint pain, as well as pharyngitis, jaundice,
      and rheumatoid arthritis in traditional Chinese medicine. However, there is no
      scientific evidence which supports the use in the literature. AIM OF THE STUDY:
      To investigate the anti-nociceptive and anti-inflammatory effects of ethanol
      extract of C. crassifolius. MATERIALS AND METHODS: Anti-nociceptive actions of C.
      crassifolius were assessed in mice using the hot-plate test, acetic acid-induced
      writhing test, and formalin test. Anti-inflammatory effects of C. crassifolius
      were determined in three animal models: acetic acid-induced capillary
      permeability accentuation in mice, carrageenan-induced edema of the hind paw in
      rats, and cotton pellet-induced granuloma formation in rats. RESULTS: Ethanol
      extract of C. crassifolius showed no significant anti-nociceptive activity in the
      hot-plate test. However, extract at dosages of 45, 90 and 180 mg/kg significantly
      reduced acetic acid-induced writhing by 28.89% (P<0.05), 38.37% (P<0.05), and
      56.53% (P<0.001), respectively. The extract also caused marked dose-related
      inhibition of formalin-induced pain in the second phase (P<0.05 for 45 mg/kg,
      P<0.001 for 90 and 180 mg/kg extract). C. crassifolius extract at dosages of 45,
      90 and 180 mg/kg significantly reduced acetic acid-induced capillary permeability
      accentuation in mice by 26.18% (P<0.05), 65.70% (P<0.001), and 79.19% (P<0.001),
      and suppressed carrageenan-induced paw edema by 21.28% (P<0.05), 30.69% (P<0.01),
      and 49.17% (P<0.001) at 6 h after carrageenan injection, respectively. 180 mg/kg
      of the extract also showed significant activity against carrageenan-induced paw
      edema at 4 h. At 90 and 180 mg/kg, the extract inhibited cotton pellet-induced
      granuloma formation in rats. CONCLUSIONS: These results collectively demonstrate
      that the ethanol extract of C. crassifolius possesses peripheral anti-nociceptive
      and anti-inflammatory effects, providing evidence to rationalize the traditional
      use of C. crassifolius for the treatment of pain and inflammation.

PMID- 22617378
TI  - Three decades of twin births in the United States, 1980-2009.
AB  - The number of twins has doubled and the rate of twin births has risen by more
      than three-fourths over the three decades 1980-2009. Increases in twin birth
      rates averaged more than 2 percent annually from 1980 to 2004, but the pace of
      increase slowed to less than 1 percent from 2005 to 2009. The increase in
      twinning over the three decades has been widespread, occurring across age and
      race and Hispanic origin groups, and in all states within the United States. The
      largest increases have been among non-Hispanic white women and mothers aged 30
      and over. Older maternal age accounts for about one-third of the growth in the
      twinning rate over this period. The increased availability and use of infertility
      treatments likely explains much of the remainder of the rise (9,10). Similar
      increasing trends in multiple births associated with both maternal age and
      infertility therapies have been observed in Western Europe and other countries
      during the 1980s and 1990s (10,12). The study of multiple births is important
      because of their elevated health risks and accompanying greater health care costs
      (6). The rise in twinning has influenced the upward trend in key infant health
      indicators such as preterm and low birthweight rates during the 1980s and 1990s
      (8). An estimated additional 865,000 twins were born in the United States over
      the study period due to rising rates; more than one-half of these infants were
      low birthweight, and 1 in 10 were very low birthweight (3,4,13). New information
      soon to be available from the 2003 revision of the U.S. Standard Certificate of
      Live Birth and the U.S. Standard Report of Fetal Death on topics such as use of
      infertility treatment and admission to a neonatal intensive care unit, will
      further expand understanding of the causes and risks of multiple-gestation
      pregnancies.

PMID- 22617379
TI  - Endovascular therapy for overcoming challenges presented with blunt abdominal
      aortic injury.
AB  - Blunt abdominal aortic injury (BAAI) is a rare and lethal injury requiring
      surgical management. Injury patterns can be complex and surgical strategy should
      accommodate specific case circumstances. Endovascular solutions appear
      appropriate and preferred in certain cases of BAAI, which, however, may not be
      applicable due to device limitations in regard to patient anatomy and limited
      operating room capability. However, endovascular therapy can be pursued with
      limited fluoroscopy capability and consumable availability providing a solution
      that is expeditious and effective for select cases of BAAI.

PMID- 22617380
TI  - A new necessary condition for Turing instabilities.
AB  - Reactivity (a.k.a initial growth) is necessary for diffusion driven instability
      (Turing instability). Using a notion of common Lyapunov function we show that
      this necessary condition is a special case of a more powerful (i.e. tighter)
      necessary condition. Specifically, we show that if the linearised reaction matrix
      and the diffusion matrix share a common Lyapunov function, then Turing
      instability is not possible. The existence of common Lyapunov functions is
      readily checked using semi-definite programming. We apply this result to the
      Gierer-Meinhardt system modelling regenerative properties of Hydra, the
      Oregonator, to a host-parasite-hyperparasite system with diffusion and to a
      reaction-diffusion-chemotaxis model for a multi-species host-parasitoid
      community.

PMID- 22617381
TI  - Mosquito management in the face of natural selection.
AB  - The sterile insect technique (SIT) is an appealing method for managing mosquito
      populations while avoiding the environmental and social costs associated with
      more traditional control strategies like insecticide application. Success of SIT,
      however, hinges on sterile males being able to compete for females. As a result,
      heavy and/or continued use of SIT could potentially diminish its efficacy if
      prolonged treatments result in selection for female preference against sterile
      males. In this paper we extend a general differential equation model of mosquito
      dynamics to consider the role of female choosiness in determining the long-term
      usefulness of SIT as a management option. We then apply optimal control theory to
      our model and show how natural selection for female choosiness fundamentally
      alters management strategies. Our study calls into question the benefits
      associated with developing SIT as a management strategy, and suggests that effort
      should be spent studying female mate choice in order to determine its relative
      importance and how likely it is to impact SIT treatment goals.

PMID- 22617382
TI  - A biologically inspired meta-control navigation system for the Psikharpax rat
      robot.
AB  - A biologically inspired navigation system for the mobile rat-like robot named
      Psikharpax is presented, allowing for self-localization and autonomous navigation
      in an initially unknown environment. The ability of parts of the model (e.g. the
      strategy selection mechanism) to reproduce rat behavioral data in various maze
      tasks has been validated before in simulations. But the capacity of the model to
      work on a real robot platform had not been tested. This paper presents our work
      on the implementation on the Psikharpax robot of two independent navigation
      strategies (a place-based planning strategy and a cue-guided taxon strategy) and
      a strategy selection meta-controller. We show how our robot can memorize which
      was the optimal strategy in each situation, by means of a reinforcement learning
      algorithm. Moreover, a context detector enables the controller to quickly adapt
      to changes in the environment-recognized as new contexts-and to restore
      previously acquired strategy preferences when a previously experienced context is
      recognized. This produces adaptivity closer to rat behavioral performance and
      constitutes a computational proposition of the role of the rat prefrontal cortex
      in strategy shifting. Moreover, such a brain-inspired meta-controller may provide
      an advancement for learning architectures in robotics.

PMID- 22617383
TI  - Daughter B cells are not created equal: asymmetric segregation of antigen during
      B cell division.

PMID- 22617384
TI  - Noncoding RNAs link PARP1 to heterochromatin.

PMID- 22617385
TI  - Heterochronic parabiosis for the study of the effects of aging on stem cells and
      their niches.
AB  - Aging is unmistakable and undeniable in mammals. Interestingly, mice develop
      cataracts, muscle atrophy, osteoporosis, obesity, diabetes and cognitive deficits
      after just 2-3 postnatal years, while it takes seven or more decades for the same
      age-specific phenotypes to develop in humans. Thus, chronological age corresponds
      differently with biological age in metazoan species and although many theories
      exist, we do not understand what controls the rate of mammalian aging. One
      interesting idea is that species-specific rate of aging represents a ratio of
      tissue attrition to tissue regeneration. Furthermore, current findings suggest
      that the age-imposed biochemical changes in the niches of tissue stem cells
      inhibit performance of this regenerative pool, which leads to the decline of
      tissue maintenance and repair. If true, slowing down stem cell and niche aging,
      thereby promoting tissue regeneration, could slow down the process of tissue and
      organismal aging. In this regard, recent studies of heterochronic parabiosis
      provide important clues as to the mechanisms of stem cell aging and suggest novel
      strategies for enhancing tissue repair in the old. Here we review current
      literature on the relationship between the vigor of tissue stem cells and the
      process of aging, with an emphasis on the rejuvenation of old tissues by the
      extrinsic modifications of stem cell niches.

PMID- 22617386
TI  - TOR links starvation responses to telomere length maintenance.
AB  - Telomeres are nucleoprotein structures that protect the ends of eukaryotic
      chromosomes and play important roles in ensuring the genome's integrity. Telomere
      length is maintained by complex mechanisms that ensure length homeostasis. Recent
      work has linked telomere length maintenance to the Tor protein kinases, which are
      central regulators of cellular growth. Here we summarize these results, which
      suggest a link between nutrient availability, telomere length maintenance and
      chronological lifespan.

PMID- 22617387
TI  - Selective blockade of tumor angiogenesis.
AB  - Blocking tumor angiogenesis is an important goal of cancer therapy, but
      clinically approved anti-angiogenic agents suffer from limited efficacy and
      adverse side effects, fueling the need to identify alternative angiogenesis
      regulators. Tumor endothelial marker 8 (TEM8) is a highly conserved cell surface
      receptor overexpressed on human tumor vasculature. Genetic disruption of Tem8 in
      mice revealed that TEM8 is important for promoting tumor angiogenesis and tumor
      growth but dispensable for normal development and wound healing. The induction of
      TEM8 in cultured endothelial cells by nutrient or growth factor deprivation
      suggests that TEM8 may be part of a survival response pathway that is activated
      by tumor microenvironmental stress. In preclinical studies, antibodies targeted
      against the extracellular domain of TEM8 inhibited tumor angiogenesis and blocked
      the growth of multiple human tumor xenografts. Anti-TEM8 antibodies augmented the
      activity of other anti-angiogenic agents, vascular targeting agents and
      conventional chemotherapeutic agents and displayed no detectable toxicity. Thus,
      anti-TEM8 antibodies provide a promising new tool for selective blockade of
      neovascularization associated with cancer and possibly other angiogenesis
      dependent diseases.

PMID- 22617388
TI  - Bortezomib induces heme oxygenase-1 expression in multiple myeloma.
AB  - Multiple myeloma (MM) is a progressive malignant disorder characterized by
      accumulation of plasma cells in the bone marrow. MM remains an incurable disease
      with a 5-y survival rate of approximately 40%. While clinical response rates to
      first line chemotherapeutics are high, disease relapse is inevitable, and occurs
      because a small fraction of the original myeloma cells appear to be resistant to
      treatment. Heme oxygenase-1 (HO-1) is an Nrf2 transcription factor-regulated gene
      that is commonly induced following oxidative stress and cellular injury,
      functioning to decrease oxidative stress and inflammatory responses, protecting
      against apoptosis and altering the cell cycle. We and others have highlighted the
      role of HO-1 in providing cellular protection against chemotherapeutic drugs in a
      number of cancer cells, which we have highlighted here in this Extra View.
      Furthermore, we explored the expression of HO-1 in multiple myeloma cells in
      response to the key anti-myeloma drugs bortezomib and lenalidomide. We show here
      for the first time that bortezomib increases HO-1 expression in a time- and
      concentration-dependent manner. Moreover, we also observe that HO-1 is increased
      in lenalidomide-resistant MM cell lines. Altogether, we highlight a possible role
      for HO-1 in basal and acquired chemoresistance in MM.

PMID- 22617389
TI  - Why is F19Ap53 unable to bind MDM2? Simulations suggest crack propagation
      modulates binding.
AB  - Why doesn't the F19A mutant of p53 bind to MDM2? Binding thermodynamics have
      suggested that the loss of packing interactions upon mutating Phe into Ala
      sidechain results in destabilizing the binding free energy between p53 and MDM2.
      Does this mutation also modulate the initial recognition between p53 and MDM2? We
      look at atomistic computer simulations of the process of the initial encounter
      between wild type p53 peptide and its F19A mutant with the N-terminal domain of
      MDM2. These simulations show that binding is characterized by a complex multistep
      process. It starts with the capture of F19 of wild type p53 by certain residues
      in the MDM2 binding pocket. This initial step anchors the peptide onto the
      surface of MDM2, and with the consequent reduction in the search space of the
      peptide, the peptide docks into the partially occluded surface of MDM2. This is
      similar to a crack forming in an otherwise occluded hydrophobic cavity in MDM2,
      and the peptide, docked through F19, modulates the propagation of this crack,
      which subsequently results in the stepwise docking of the rest of the peptide
      through insertions of W23 and L26. The lack of the bulky sidechain of F in the
      F19A mutant results in the absence of the initial "grasp" complex, and hence the
      mutant peptide diffuses randomly on the surface of MDM2 without binding. This is
      the first such demonstration of the possibility that a "kinetic" effect may
      partly underlie the destabilized thermodynamics of binding of F19A and is a
      feature that appears to be conserved in evolution. The observations by Wallace et
      al. (Mol Cell 2006; 23:251-63) that despite the inability of F19A to bind at the
      N-terminal domain of MDM2, it gets ubiquitinated, can now be partly understood
      based on a mechanism whereby the occupation of the binding pocket by
      ligands/peptides induces, via crack propagation and the dynamics of gatekeeper
      Y100, the ubiquitination signal for interactions between the acidic domain of
      MDM2 and the DNA binding domain of p53.

PMID- 22617390
TI  - The specific contributions of cohesin-SA1 to cohesion and gene expression:
      implications for cancer and development.
AB  - Besides its well-established role in sister chromatid cohesion, cohesin has
      recently emerged as major player in the organization of interphase chromatin.
      Such important function is related to its ability to entrap two DNA segments also
      in cis, thereby facilitating long-range DNA looping which is crucial for
      transcriptional regulation, organization of replication factories and V(D)J
      recombination. Vertebrate somatic cells have two different versions of cohesin,
      containing Smc1, Smc3, Rad21/Scc1 and either SA1 or SA2, but their functional
      specificity has been largely ignored. We recently generated a knockout mouse
      model for the gene encoding SA1, and found that this protein is essential to
      complete embryonic development. Cohesin-SA1 mediates cohesion at telomeres, which
      is required for their replication. Telomere defects in SA1- deficient cells
      provoke chromosome segregation errors resulting in aneuploidy despite robust
      centromere cohesion. This aneuploidy could explain why heterozygous animals have
      an earlier onset of tumorigenesis. In addition, the genome-wide distribution of
      cohesin changes dramatically in the absence of SA1, and the complex shows reduced
      accumulation at promoters and CTCF sites. As a consequence, gene expression is
      altered, leading to downregulation of biological processes related to a
      developmental disorder linked to cohesin function, the Cornelia de Lange Syndrome
      (CdLS). These results point out a prominent role of cohesin-SA1 in
      transcriptional regulation, with clear implications in the etiology of CdLS.

PMID- 22617391
TI  - Cognitive ability in early adulthood is associated with later suicide and suicide
      attempt: the role of risk factors over the life course.
AB  - BACKGROUND: Cognitive ability/intelligence quotient (IQ) in youth has previously
      been associated with subsequent completed and attempted suicide, but little is
      known about the mechanisms underlying the associations. This study aims to assess
      the roles of various risk factors over the life course in explaining the observed
      relationships. METHOD: The present investigation is a cohort study based on data
      on IQ test performance and covariates, recorded on 49 321 Swedish men conscripted
      in 1969-1970, at ages 18-20 years. Information on suicides and hospital
      admissions for suicide attempt up to the age of 57 years, childhood and adult
      socio-economic position, and adult family formation, was obtained from linkage to
      national registers. RESULTS: Lower IQ was associated with increased risks of both
      suicide and suicide attempt during the 36 years of follow-up. The associations
      followed a dose-response pattern. They were attenuated by approximately 45% in
      models controlling for social background, mental ill-health, aspects of
      personality and behavior, adult socio-economic position and family formation.
      Based on one-unit decreases in IQ test performance on a nine-point scale, the
      hazard ratios between ages 35 and 57 years were: for suicide 1.19 [95% confidence
      interval (CI) 1.13-1.25], fully adjusted 1.10 (95% CI 1.04-1.18); and for suicide
      attempt 1.25 (95% CI 1.20-1.31), fully adjusted 1.14 (95% CI 1.09-1.20).
      CONCLUSIONS: Cognitive ability was found to be associated with subsequent
      completed and attempted suicide. The associations were attenuated by 45% after
      controlling for risk factors measured over the life course. Psychiatric
      diagnosis, maladjustment and aspects of personality in young adulthood, and
      social circumstances in later adulthood, contributed in attenuating the
      associations.

PMID- 22617392
TI  - Effect of additional speed endurance training on performance and muscle
      adaptations.
AB  - PURPOSE: The present study examined the effect of additional speed endurance
      training (SET) during the season on muscle adaptations and performance of trained
      soccer players. METHODS: Eighteen subelite soccer players performed one session
      with six to nine 30-s intervals at an intensity of 90%-95% of maximal intensity
      (SET) a week for 5 wk (SET intervention). Before and after the SET intervention,
      the players carried out the Yo-Yo intermittent recovery level 2 (Yo-Yo IR2) test,
      a sprint test (10 and 30 m), and an agility test. In addition, seven of the
      players had a resting muscle biopsy specimen taken and they carried out a running
      protocol on a motorized treadmill before and after the SET intervention. RESULTS:
      After the SET intervention, the Yo-Yo IR2 test (n = 13) performance was 11%
      better (P < 0.05), whereas sprint (n = 15) and agility (n = 13) performances were
      unchanged. The expression of the monocarboxylate transporter 1 (n = 6) was 9%
      higher (P < 0.05). and the expression of the Na(+)/K(+) pump subunit beta(1) (n =
      6) was 13% lower (P < 0.05) after the SET intervention. The Na(+)/K(+) pump
      subunits alpha(1), alpha(2), as well as the monocarboxylate transporter 4 and the
      Na(+)/H(+) exchanger 1 (n = 6) were unchanged. After the SET intervention, the
      relative number of Type IIx fibers and oxygen consumption at 10 km.h(-1) were
      lower (P < 0.05), whereas VO(2max) was unchanged. CONCLUSIONS: In conclusion,
      adding ~30 min of SET once a week during the season for trained soccer players
      did lead to an improved ability to perform repeated high-intensity exercise, with
      a concomitant increase in the expression of monocarboxylate transporter 1 and an
      improved running economy.

PMID- 22617393
TI  - Neural response to pictures of food after exercise in normal-weight and obese
      women.
AB  - PURPOSE: This study examined the effect of a bout of moderate-to-vigorous (MV)
      exercise on the neural response to pictures of food (used to index food
      motivation) in normal-weight and obese women. Secondary outcomes included energy
      intake and physical activity (PA) over 24 h. METHODS: Using a crossover design,
      18 normal-weight and 17 obese women completed a morning-time, 45-min exercise
      bout (treadmill at 3.8 mph; 0% grade) and were subsequently followed for 24 h.
      This was counterbalanced by a control day with no exercise bout. To assess the
      effect of exercise on food motivation, participants were shown pictures of food
      and flowers (control) after exercise. Neural activity was concurrently monitored
      using electroencephalogram for the late positive potential (LPP) component of the
      event-related potential (ERP) and compared with the LPP response on the
      nonexercise day. After testing, weighed food records were kept for the duration
      of each day. PA was monitored, via accelerometry, over each day. RESULTS: There
      was not a significant body mass index (BMI) group * exercise condition * picture
      type interaction for LPP amplitude; however, when participants were pooled, the
      exercise condition resulted in lower LPP amplitude waveforms in response to food
      pictures than the nonexercise condition (F = 4.25, P = 0.048). There were no
      differences in energy or macronutrient intake (P > 0.05). The exercise condition
      resulted in significantly more PA than the nonexercise condition, and there was a
      significant BMI group * exercise condition interaction for MV PA (F = 4.48, P =
      0.043) with obese women showing less MV PA. CONCLUSIONS: A bout of MV exercise
      decreases neurologically determined food motivation (i.e., the LPP event-related
      potential), but the effect of BMI is unclear. In addition, a morning-time
      exercise bout significantly increases 24-h PA; 24-h MV PA differed according to
      BMI.

PMID- 22617394
TI  - The 6-min push test is reliable and predicts low fitness in spinal cord injury.
AB  - PURPOSE: The objective of this study is to assess 6-min push test (6MPT)
      reliability, determine whether the 6MPT is sensitive to fitness differences, and
      assess if 6MPT distance predicts fitness level in persons with spinal cord injury
      (SCI) or disease. METHODS: Forty individuals with SCI who could self-propel a
      manual wheelchair completed an incremental arm crank peak oxygen consumption
      assessment and two 6MPTs across 3 d (37% tetraplegia (TP), 63% paraplegia (PP),
      85% men, 70% white, 63% Hispanic, mean age = 34 +/- 10 yr, mean duration of
      injury = 13 +/- 10 yr, and mean body mass index = 24 +/- 5 kg.m). Intraclass
      correlation and Bland-Altman plots assessed 6MPT distance (m) reliability. Mann
      Whitney U test compared 6MPT distance (m) of high and low fitness groups for TP
      and PP. The fitness status prediction was developed using N = 30 and validated in
      N = 10 (validation group (VG)). A nonstatistical prediction approach, below or
      above a threshold distance (TP = 445 m and PP = 604 m), was validated
      statistically by binomial logistic regression. Accuracy, sensitivity, and
      specificity were computed to evaluate the threshold approach. RESULTS: Intraclass
      correlation coefficients exceeded 0.90 for the whole sample and the TP/PP
      subsets. High fitness persons propelled farther than low fitness persons for both
      TP/PP (both P < 0.05). Binomial logistic regression (P < 0.008) predicted the
      same fitness levels in the VG as the threshold approach. In the VG, overall
      accuracy was 70%. Eighty-six percent of low fitness persons were correctly
      identified (sensitivity), and 33% of high fitness persons were correctly
      identified (specificity). CONCLUSION: The 6MPT may be a useful tool for SCI
      clinicians and researchers. 6MPT distance demonstrates excellent reliability and
      is sensitive to differences in fitness level. 6MPT distances less than a
      threshold distance may be an effective approach to identify low fitness in person
      with SCI.

PMID- 22617395
TI  - Validity of the SenseWear(r) Armband to predict energy expenditure in pregnant
      women.
AB  - Few valid, objective methods exist to quantify physical activity and predict
      energy expenditure (EE) during pregnancy. PURPOSE: The purpose of this study was
      to evaluate the validity of the SenseWear Mini armband monitor (SWA) (BodyMedia,
      Pittsburgh, PA) to estimate EE in pregnant women. METHODS: Thirty healthy
      pregnant women (22-24 wk of gestation) completed a series of activities of daily
      living (typing, laundry, sweeping, and treadmill walking: 2.0, 2.5, 3.0, and 3.0
      mph, 3% incline) while EE was estimated by the SWA and measured by indirect
      calorimetry (IC). The SWA data were processed using both the v2.2 algorithm and
      the newer v5.2 algorithm. The estimated EE values were compared with the measured
      EE values using a three-way (method * algorithm * activity) mixed model ANOVA.
      Least square means +/- SE were estimated in the model. Significance was set at P
      < 0.05. RESULTS: The analyses revealed a significant method (IC vs. SWA) *
      algorithm (v5.2 vs. v2.2) interaction with significantly smaller error (IC-SWA)
      for the newer v5.2 algorithm (-0.57 +/- 0.06 kcal.min(-1)) than the older v2.2
      algorithm (-0.78 +/- 0.06 kcal.min(-1)). The SWA significantly overestimated EE
      for all activities, except inclined walking. The average mean absolute percentage
      error was considerably lower for the new algorithm (22%) than that for the older
      algorithm (35%). The average individual correlation coefficients revealed good
      overall agreement between the SWA and the IC (v5.2, mean r = 0.93; v2.2, mean r =
      0.87). CONCLUSION: Overall, the SWA correlated well with IC; however, EE was
      significantly overestimated during most activities. Future studies should develop
      pregnancy-specific algorithms and assess validity of the SWA at all stages of
      pregnancy to further improve prediction of EE in this population.

PMID- 22617396
TI  - Preexercise aminoacidemia and muscle protein synthesis after resistance exercise.
AB  - PURPOSE: We have previously shown that the aminoacidemia caused by the
      consumption of a rapidly digested protein after resistance exercise enhances
      muscle protein synthesis (MPS) more than the amino acid (AA) profile associated
      with a slowly digested protein. Here, we investigated whether differential
      feeding patterns of a whey protein mixture commencing before exercise affect
      postexercise intracellular signaling and MPS. METHODS: Twelve resistance-trained
      males performed leg resistance exercise 45 min after commencing each of three
      volume-matched nutrition protocols: placebo (PLAC, artificially sweetened water),
      BOLUS (25 g of whey protein + 5 g of leucine dissolved in artificially sweetened
      water; 1 * 500 mL), or PULSE (15 * 33-mL aliquots of BOLUS drink every 15 min).
      RESULTS: The preexercise rise in plasma AA concentration with PULSE was
      attenuated compared with BOLUS (P < 0.05); this effect was reversed after
      exercise, with two-fold greater leucine concentrations in PULSE compared with
      BOLUS (P < 0.05). One-hour postexercise, phosphorylation of p70 S6K(thr389) and
      rpS6(ser235/6) was increased above baseline with BOLUS and PULSE, but not PLAC (P
      < 0.05); furthermore, PULSE > BOLUS (P < 0.05). MPS throughout 5 h of recovery
      was higher with protein ingestion compared with PLAC (0.037 +/- 0.007), with no
      differences between BOLUS or PULSE (0.085 +/- 0.013 vs. 0.095 +/- 0.010%.h(-1),
      respectively, P = 0.56). CONCLUSIONS: Manipulation of aminoacidemia before
      resistance exercise via different patterns of intake of protein altered plasma AA
      profiles and postexercise intracellular signaling. However, there was no
      difference in the enhancement of the muscle protein synthetic response after
      exercise. Protein sources producing a slow AA release, when consumed before
      resistance exercise in sufficient amounts, are as effective as rapidly digested
      proteins in promoting postexercise MPS.

PMID- 22617397
TI  - Effect of shared environmental factors on exercise behavior from age 7 to 12
      years.
AB  - INTRODUCTION: The aim of this study was to investigate the relative influence of
      genetic and environmental factors on children's leisure time exercise behavior
      through the classic twin design. METHODS: Data were taken from The Netherlands
      Twin Register. The twins were 7 (n = 3966 subjects), 10 (n = 3562), and 12-yr
      olds (n = 8687), with longitudinal data for 27% of the sample. Parents were asked
      to indicate the children's regular participation in leisure time exercise
      activities, including frequency and duration. Resemblance between monozygotic and
      dizygotic twins for weekly MET-hours spent on exercise activities was analyzed as
      a function of their genetic relatedness. RESULTS: Average weekly MET-hours
      increased with age for both boys (age 7 yr: 14.0 (SD = 11.8); age 10 yr: 22.6 (SD
      = 18.7); age 12 yr: 28.4 (SD = 24.9)) and girls (age 7 yr: 9.7 (SD = 9.5); age 10
      yr: 15.3 (SD = 15.1); age 12 yr: 19.3 (SD = 19.8)). Around 13% of boys and girls
      across all age groups did not participate in any regular leisure time exercise
      activities. Tracking of exercise behavior from age 7 to 12 yr was modest (0.168 <
      r < 0.534). For boys, genetic effects accounted for 24% (confidence interval, 18%
      30%) of the variance at age 7 yr, 66% (53%-81%) at age 10 yr, and 38% (32%-46%)
      at age 12 yr. For girls, this was 22% (15%-30%), 16% (9%-24%), and 36% (30%-43%),
      respectively. Environmental influences shared by children from the same family
      explained 71%, 25%, and 50% of the variance in boys (age 7, 10, and 12 yr) and
      67%, 72%, and 53% in girls. The shared environment influencing exercise behavior
      was partially different between boys and girls. CONCLUSION: Our results stress
      the important role of shared environment for exercise behavior in young children.

PMID- 22617399
TI  - Quantification of hand and forearm muscle forces during a maximal power grip
      task.
AB  - PURPOSE: The aim of this study was to estimate muscle and joint forces during a
      power grip task. Considering the actual lack of quantification of such internal
      variables, this information would be essential for sports sciences, medicine, and
      ergonomics. This study also contributed to the advancement of scientific
      knowledge concerning hand control during power grip. METHODS: A specially
      designed apparatus combining both an instrumented handle and a pressure map was
      used to record the forces at the hand/handle interface during maximal exertions.
      Data were processed such that the forces exerted on 25 hand anatomical areas were
      determined. Joint angles of the five fingers and the wrist were also computed
      from synchronized kinematic measurements. These processed data were used as input
      of a hand/wrist biomechanical model, which includes 23 degrees of freedom and 42
      muscles to estimate muscle and joint forces. RESULTS: Greater forces were applied
      on the distal phalanges of the long fingers compared with the middle and the
      proximal ones. Concomitantly, high solicitations were observed for FDP muscles. A
      large cocontraction level of extensor muscles was also estimated by the model and
      confirmed previously reported activities and injuries of extensor muscles related
      to the power grip. Quantifying hand internal loadings also resulted in new
      insights into the thumb and the wrist biomechanics. Output muscle tension ratios
      were all in smaller ranges than the ones reported in the literature. CONCLUSIONS:
      Including wrist and finger interactions in this hand model provided new
      quantification of muscle load sharing, cocontraction level, and biomechanics of
      the hand. Such information could complete future investigations concerning handle
      ergonomics or pathomechanisms of hand musculoskeletal disorders.

PMID- 22617398
TI  - What predicts functional outcome after treatment for patellofemoral pain?
AB  - PURPOSE: Although physical therapy is known to be effective in treating
      patellofemoral pain (PFP), there is considerable individual variation in the
      treatment response. It is unclear why some patients benefit from a specific
      treatment while others do not experience improvement. This study, using a
      prospective study design, aims to identify factors that could predict the short
      term functional outcome and account for the variation frequently seen in the
      outcome after conservative treatment of PFP. METHODS: Thirty-six patients (20
      female and 16 male with a mean age of 23.8 +/- 6.7 yr) followed a physical
      therapy rehabilitation program of 7 wk. Before this treatment, all patients were
      evaluated on subjective symptoms (pain on visual analog scales in millimeters)
      and functional performance (step test expressed as highest level, single-legged
      hop test in centimeters, and triple-hop test in centimeters). The concentric and
      eccentric knee extensor strength at 60 degrees .s(-1) and 240 degrees .s(-1)
      (N.m) were measured as well as the quadriceps muscle size by calculating the
      cross-sectional area (cm(2)) with magnetic resonance imaging. The success of the
      treatment was evaluated by the functional Kujala anterior knee pain scale. A
      linear regression model was used to identify predisposing factors for the
      functional outcome. RESULTS: The total quadriceps cross-sectional area (P =
      0.010), the eccentric average peak torque at 60 degrees .s(-1) (P = 0.015), and
      the frequency of pain at baseline (P = 0.012) have been indicated as predisposing
      variables in the short-term functional outcome after a physical therapy
      rehabilitation program for PFP (adjusted R(2) = 0.46). CONCLUSION: Patients with
      a greater quadriceps muscle size, lower eccentric knee strength, and less pain
      have a better short-term functional outcome after conservative treatment for PFP.

PMID- 22617400
TI  - Activity classification using the GENEA: optimum sampling frequency and number of
      axes.
AB  - INTRODUCTION: The GENEA shows high accuracy for classification of sedentary,
      household, walking, and running activities when sampling at 80 Hz on three axes.
      It is not known whether it is possible to decrease this sampling frequency and/or
      the number of axes without detriment to classification accuracy. The purpose of
      this study was to compare the classification rate of activities on the basis of
      data from a single axis, two axes, and three axes, with sampling rates ranging
      from 5 to 80 Hz. METHODS: Sixty participants (age, 49.4 yr (6.5 yr); BMI, 24.6
      kg.m (3.4 kg.m)) completed 10-12 semistructured activities in the laboratory and
      outdoor environment while wearing a GENEA accelerometer on the right wrist. We
      analyzed data from single axis, dual axes, and three axes at sampling rates of 5,
      10, 20, 40, and 80 Hz. Mathematical models based on features extracted from mean,
      SD, fast Fourier transform, and wavelet decomposition were built, which combined
      one of the numbers of axes with one of the sampling rates to classify activities
      into sedentary, household, walking, and running. RESULTS: Classification accuracy
      was high irrespective of the number of axes for data collected at 80 Hz (96.93%
      +/- 0.97%), 40 Hz (97.4% +/- 0.73%), 20 Hz (96.86% +/- 1.12%), and 10 Hz (97.01%
      +/- 1.01%) but dropped for data collected at 5 Hz (94.98% +/- 1.36%). CONCLUSION:
      Sampling frequencies >10 Hz and/or more than one axis of measurement were not
      associated with greater classification accuracy. Lower sampling rates and
      measurement of a single axis would result in a lower data load, longer battery
      life, and higher efficiency of data processing. Further research should
      investigate whether a lower sampling rate and a single axis affects
      classification accuracy when considering a wider range of activities.

PMID- 22617401
TI  - Strength asymmetry increases gait asymmetry and variability in older women.
AB  - PURPOSE: The aim of the research was to determine how knee extensor strength
      asymmetry influences gait asymmetry and variability because these gait parameters
      have been related to mobility and falls in older adults. METHODS: Strength of the
      knee extensors was measured in 24 older women (65-80 yr). Subjects were separated
      into symmetrical strength (SS, n = 13) and asymmetrical strength (SA, n = 11)
      groups using an asymmetry cutoff of 20%. Subjects walked at a standard speed of
      0.8 m.s and at maximal speed on an instrumented treadmill while kinetic and
      spatiotemporal gait variables were measured. Gait and strength asymmetry were
      calculated as the percentage difference between legs and gait variability as the
      coefficient of variation over 20 sequential steps. RESULTS: SA had greater
      strength asymmetry (27.4% +/- 5.5%) than SS (11.7% +/- 5.4%, P < 0.001). Averaged
      across speeds, SA had greater single- (7.1% vs. 2.5%) and double-limb support
      time asymmetry (7.0% vs. 4.3%) than SS and greater single-limb support time
      variability (9.7% vs. 6.6%, all P < 0.05). Group * speed interactions occurred
      for weight acceptance force variability (P = 0.02) and weight acceptance force
      asymmetry (P = 0.017) with greater variability at the maximal speed in SA (5.0%
      +/- 2.4% vs. 3.7% +/- 1.2%) and greater asymmetry at the maximal speed in SA
      (6.4% +/- 5.3% vs. 2.5% +/- 2.3%). CONCLUSION: Gait variability and asymmetry are
      greater in older women with strength asymmetry and increase when they walk near
      their maximal capacities. The maintenance of strength symmetry, or development of
      symmetry through unilateral exercise, may be beneficial in reducing gait
      asymmetry, gait variability, and fall risk in older adults.

PMID- 22617402
TI  - Computational methods for estimating energy expenditure in human physical
      activities.
AB  - Accurate and reliable methods for assessing human physical activity (PA) energy
      expenditure (PAEE) are informative and essential for understanding individual
      behaviors and quantifying the effect of PA on disease, for PA surveillance, and
      for examining determinants of PA in different populations. This article reviews
      recent advances in the estimation of PAEE in three interrelated areas: 1) types
      of sensors worn by human subjects, 2) features extracted from the measured sensor
      signals, and 3) modeling techniques to estimate the PAEE using these features.
      The review illustrates three directions in the PAEE studies and provides
      recommendations for future research, with the aim to produce valid, reliable, and
      accurate assessment of PAEE from wearable sensors.

PMID- 22617403
TI  - Tempol suppresses micronuclei formation in astrocytes of newborn rats exposed to
      50-Hz, 10-mT electromagnetic fields under bleomycin administration.
AB  - A number of epidemiological studies have suggested that exposure to environmental
      and occupational electromagnetic fields (EMFs) contribute to the induction of
      brain tumors. The aim of this study was to investigate the mutagenetic effects of
      co-exposure to 50-Hz, 10-mT EMFs and bleomycin (BLM) using an ex vivo newborn rat
      astrocyte micronucleus assay. We also investigated whether the mutagenetic
      effects of EMFs were related to active oxygen species by using 4-hydroxy-2,2,6,6
      tetramethyl piperidine-1-oxyl (tempol), a superoxide radical scavenger. Three-day
      old male Sprague-Dawley rats were co-exposed to 50-Hz EMFs and BLM (5 or 10mg/kg
      body weight (BW)) in each group (n=6; total 6 group), and were co-exposed to 50
      Hz EMFs and 10mg/kg BW BLM with administration of 200MUmol/kg BW tempol in each
      group (total 4 group). Brain cells were dissociated into single cells, cultured
      for 96h, incubated with an antibody against glial fibrillary acidic protein, and
      stained with acridine orange. The frequency of micronucleated astrocytes was
      determined using a fluorescence microscope. The frequency of micronucleated
      astrocytes in the 10mg/kg BW bleomycin plus EMF exposure group (Mean+/-SD: 19.8+/
      5.20/00) was 1.6 times higher than that in the 10mg/kg BW bleomycin plus sham
      exposure group (Mean+/-SD: 12.7+/-3.30/00) (p<0.05). Analysis of the frequency of
      micronuclei in astrocytes after co-exposure to EMF and bleomycin for 72h and
      administration of tempol revealed that, in the EMF exposure group, the frequency
      of micronuclei in rats administered with 10mg/kg BW bleomycin and treated with
      tempol (Mean+/-SD: 11.2+/-1.90/00) was 40% of that in rats administered with the
      same dose of bleomycin and physiological saline (Mean+/-SD: 28.0+/-15.00/00)
      (p<0.01). Results of the current study suggested that the mechanism responsible
      for the elevated frequency of micronuclei in astrocytes of rats co-exposed to BLM
      and EMFs is related to active oxygen species.

PMID- 22617404
TI  - Hospitalization for stroke in U.S. hospitals, 1989-2009.
AB  - Stroke remains one of the most significant U.S. health problems (6). Although the
      stroke hospitalization rate has declined, in 2009 there were still almost 1
      million hospitalizations for stroke. Many stroke patients, upon discharge, went
      to another short-stay hospital or a long-term care institution. In addition,
      outpatient or in-home services (including rehabilitation) are often provided to
      those who have had a stroke, to prevent future strokes and to restore functioning
      (6,7). In 2011, the U.S. Department of Health and Human Services announced its
      "Million Hearts" campaign, which aims to prevent 1 million heart attacks and
      strokes over the next 5 years (8). Efforts like this are especially important
      because the baby boomer population is aging into the years when strokes are more
      common. It is important to continue to track the number and rate of stroke
      hospitalizations, in order to gauge the effects of campaigns like Million Hearts
      as well as the effectiveness of provisions in health care legislation (including
      the Patient Protection and Affordable Care Act) that promote preventive care and
      coordination of care.

PMID- 22617405
TI  - Aseptic laboratory techniques: plating methods.
AB  - Microorganisms are present on all inanimate surfaces creating ubiquitous sources
      of possible contamination in the laboratory. Experimental success relies on the
      ability of a scientist to sterilize work surfaces and equipment as well as
      prevent contact of sterile instruments and solutions with non-sterile surfaces.
      Here we present the steps for several plating methods routinely used in the
      laboratory to isolate, propagate, or enumerate microorganisms such as bacteria
      and phage. All five methods incorporate aseptic technique, or procedures that
      maintain the sterility of experimental materials. Procedures described include
      (1) streak-plating bacterial cultures to isolate single colonies, (2) pour
      plating and (3) spread-plating to enumerate viable bacterial colonies, (4) soft
      agar overlays to isolate phage and enumerate plaques, and (5) replica-plating to
      transfer cells from one plate to another in an identical spatial pattern. These
      procedures can be performed at the laboratory bench, provided they involve non
      pathogenic strains of microorganisms (Biosafety Level 1, BSL-1). If working with
      BSL-2 organisms, then these manipulations must take place in a biosafety cabinet.
      Consult the most current edition of the Biosafety in Microbiological and
      Biomedical Laboratories (BMBL) as well as Material Safety Data Sheets (MSDS) for
      Infectious Substances to determine the biohazard classification as well as the
      safety precautions and containment facilities required for the microorganism in
      question. Bacterial strains and phage stocks can be obtained from research
      investigators, companies, and collections maintained by particular organizations
      such as the American Type Culture Collection (ATCC). It is recommended that non
      pathogenic strains be used when learning the various plating methods. By
      following the procedures described in this protocol, students should be able to:
      Perform plating procedures without contaminating media.     Isolate single
      bacterial colonies by the streak-plating method.     Use pour-plating and spread
      plating methods to determine the concentration of bacteria.     Perform soft agar
      overlays when working with phage.     Transfer bacterial cells from one plate to
      another using the replica-plating procedure.     Given an experimental task,
      select the appropriate plating method.

PMID- 22617407
TI  - Functional evidence for an active role of B-type natriuretic peptide in cardiac
      remodelling and pro-arrhythmogenicity.
AB  - AIMS: During heart failure (HF), the left ventricle (LV) releases B-type
      natriuretic peptide (BNP), possibly contributing to adverse cardiovascular events
      including ventricular arrhythmias (VAs) and LV remodelling. We investigated the
      cardiac effects of chronic BNP elevation in healthy mice and compared the results
      with a model of HF after myocardial infarction (PMI mice). METHODS AND RESULTS:
      Healthy mice were exposed to circulating BNP levels (BNP-Sham) similar to those
      measured in PMI mice. Telemetric surface electrocardiograms showed that in
      contrast with fibrotic PMI mice, electrical conduction was not affected in BNP
      Sham mice. VAs were observed in both BNP-Sham and PMI but not in Sham mice.
      Analysis of heart rate variability indicated that chronic BNP infusion increased
      cardiac sympathetic tone. At the cellular level, BNP reduced Ca(2+) transients
      and impaired Ca(2+) reuptake in the sarcoplasmic reticulum, in line with blunted
      SR Ca(2+) ATPase 2a and S100A1 expression. BNP increased Ca(2+) spark frequency,
      reflecting Ca(2+) leak through ryanodine receptors, elevated diastolic Ca(2+),
      and promoted spontaneous Ca(2+) waves. Similar effects were observed in PMI mice.
      Most of these effects were reduced in BNP-Sham and PMI mice by the selective
      beta1-adrenergic blocker metoprolol. CONCLUSION: Elevated BNP levels, by inducing
      sympathetic overdrive and altering Ca(2+) handling, promote adverse cardiac
      remodelling and VAs, which could account in part for the progression of HF after
      MI. The early use of beta-blockers to prevent the deleterious effects of chronic
      BNP exposure may be beneficial in HF.

PMID- 22617410
TI  - Collaborating for impact: a multilevel early childhood obesity prevention
      initiative.
AB  - This article presents Healthy Kids, Healthy Futures, a multilevel initiative in
      Boston, Massachusetts, which brings major institutions' missions and resources
      together to address early childhood obesity prevention. Programming is designed
      to facilitate healthy eating and physical activity in preschool children's home,
      school, and community environments by engaging parents and early childhood
      educators in the places where they live, learn, and play. This article describes
      how established interventions were implemented in a novel setting to engage the
      parents of children attending Head Start and staff, and presents pilot data from
      the first 2 years of the initiative. Healthy Kids, Healthy Futures is a feasible
      initiative, which has shown concrete, positive results that can be replicated.

PMID- 22617411
TI  - Implementation of an evidence-based hand hygiene program in elementary schools in
      Ghana, as part of a City-to-City partnership between Ottawa public health and
      KEEA health directorate.
AB  - Ottawa Public Health in partnership with health staff from the municipality of
      KEEA (Komenda, Edina, Eguafo, Abrem) in Ghana engaged in a city-to-city
      partnership to adapt, implement, and evaluate an evidence-based hand hygiene
      public health initiative in elementary schools in Ghana. All 4 participating
      schools gained the necessary resources to carry out proper hand hygiene practice,
      and hand hygiene practice improved. Furthermore, pupils were more likely to wash
      hands after using the toilets and teachers were better equipped to be good role
      models. Providing resources to schools was key to the success of the
      implementation. This partnership gave health and education workers in Ghana the
      tools, knowledge, and confidence to implement a simple, evidence-based, hand
      hygiene program. One other remarkable outcome is that school children were the
      initiators of a behavior change in their community.

PMID- 22617406
TI  - Myosin heavy chain isoform expression in the Vastus Lateralis muscle of aging
      African green vervet monkeys.
AB  - Non-human primates (NHP) represent an emerging animal model for the study of
      physical function, and provide opportunities for exploration of relationships of
      muscle biomolecular changes with age. One such primate model, the African green
      vervet monkey, has been used extensively in biomedical research but little is
      known regarding skeletal muscle composition, expression of myosin heavy chain
      (MHC) isoforms, and changes with age. In the present study we examined the
      effects of age on vastus lateralis (VL) muscle fiber-type composition, fiber
      cross-sectional area (CSA), and MHC isoforms expressed in 4 young and 4 older
      adult vervet monkeys. Proteomics analysis, using a human and nonhuman primate
      protein database, showed five MHC isoforms (I, IIA, IIX, IIB, and IIB') expressed
      in female vervet VL muscle, which matched the human MHC isoforms. Fast type II
      fibers predominated and no pure type IIB or IIB' containing fibers were detected.
      Hybrid fibers containing IIB/IIB' MHC decreased in the old vervets. The CSA of
      both type I and type II fibers was significantly smaller in older vervet while
      type IIA fibers showed the most severity of atrophy. The decrease of fast MHC and
      atrophy of muscle fiber with aging recapitulate observations in human VL muscle.
      These findings, along with its homology of MHC between the vervet and human
      suggested that the vervet monkey may be a suitable preclinical model for
      understanding the cellular and molecular basis of sarcopenia and for developing
      new interventions to ameliorate the impact of disorders that affect skeletal
      muscle structure and function.

PMID- 22617412
TI  - Safe n' sound: an evidence-based tool to prioritize injury messages for pediatric
      health care.
AB  - Safe N' Sound is a computer-based tool that prioritizes key injury risks for
      toddlers and infants and provides tailored feedback. The program was implemented
      in 5 pediatric sites. Caregiver risk behaviors were analyzed and compared with
      corresponding national and state morbidity and mortality data. The priority risks
      identified were generally consistent with the incidence of injury. Frequencies of
      several risk behaviors varied across sites and differences were observed across
      ages. Use of a prioritization scheme may facilitate risk behavior counseling and
      reasonably result in a decrease in injury mortality or morbidity.

PMID- 22617413
TI  - Promoting CARE: including parents in youth suicide prevention.
AB  - This study evaluated the effectiveness of augmenting a youth suicide-preventive
      intervention with a brief, home-based parent program. A total of 615 high school
      youth and their parents participated. Three suicide prevention protocols, a youth
      intervention, a parent intervention, and a combination of youth and parent
      intervention, were compared with an "intervention as usual" (IAU) group. All
      groups experienced a decline in risk factors and an increase in protective
      factors during the intervention period, and sustained these improvements over 15
      months. Results reveal that the youth intervention and combined youth and parent
      intervention produced significantly greater reductions in suicide risk factors
      and increases in protective factors than IAU comparison group.

PMID- 22617414
TI  - Participatory adaptation of an evidence-based, arthritis self-management program:
      making changes to improve program fit.
AB  - We employed community-based participatory research techniques to adapt an
      evidence-based self-management program called the Arthritis Self-Help Program for
      older African American, Hispanic, and non-Hispanic white adults. Participants and
      instructors provided multiple recommendations for program change (including
      content additions or augmentations as well as changes in program delivery) in
      telephone interviews and focus groups. Recommendations were implemented through a
      collaborative process involving diverse stakeholders. Changes implemented respond
      to the preferences and needs of participants, as well as the strengths and
      constraints of program instructors and host sites. Improved fit for participants
      may extend the program's reach and effectiveness for older adults of color. In
      addition, the adapted Arthritis Self-Help Program may make the program more
      feasible and therefore sustainable for the host sites.

PMID- 22617415
TI  - Dissemination of a tobacco cessation program for unionized workers.
AB  - Many multilevel, contextually relevant, evidenced-based health promotion programs
      are not disseminated widely. The purpose of this study is to describe the
      adaptation of a published effective tobacco-use cessation intervention, which was
      implemented and evaluated in a broader population of unionized workers partnering
      with a health and welfare fund health benefits carrier. 68 tobacco users
      enrolled. Implementation and effectiveness outcomes indicated that most
      participants (69%) completed all counseling calls and at 16 weeks' follow-up,
      30.9% reported not using tobacco. The intervention had relatively high levels of
      implementation, effectiveness, and acceptability, but low reach, highlighting
      issues arising during dissemination.

PMID- 22617416
TI  - Falls efficacy among older adults enrolled in an evidence-based program to reduce
      fall-related risk: sustainability of individual benefits over time.
AB  - Grand-scale community rollouts of evidence-based programs seldom have the
      capacity to examine long-term sustainability of beneficial effects among older
      adults. This study examined the effectiveness of A Matter of Balance/Volunteer
      Lay Leader Model, an evidence-based fall risk reduction program, to sustain fall
      related efficacy improvements among 282 older adult participants using data
      collected at 3 time points: baseline, postintervention, and 6-month follow-up. A
      linear mixed model and multilevel logistic regression models were used. Falls
      Efficacy Scale and individual item scores significantly increased from baseline
      to postintervention. While most efficacy-related scores tapered after
      postintervention, all changes remained significant at 6-month follow-up.

PMID- 22617417
TI  - Cost analysis of a community-based fall prevention program being delivered in
      South Florida.
AB  - The aim of this study was to measure the costs of delivering a fall prevention
      program by community agencies in South Florida. Cost data were collected from
      agencies participating in the delivery of Matter of Balance workshops in South
      Florida. Cost information included both initial implementation and ongoing
      workshop delivery costs. Average costs for implementation per program completer
      were $325 during the first year in which the program was offered and $176 during
      the second year of the program. Matter of Balance is a relatively inexpensive
      fall prevention program. This has implications for the further dissemination and
      sustainability of evidence-based programs for elderly individuals.

PMID- 22617418
TI  - Practice policies for older anesthesiologists in academic departments: a national
      survey of academic departmental chairpersons.
AB  - STUDY OBJECTIVES: To determine 1) which proportion of academic departments have
      policies concerning older anesthesiologists, 2) whether departments with such
      policies, particularly those related to call, had characteristics such as
      departmental size and proportions of older anesthesiologists that differed from
      departments without these policies, 3) if departments routinely screened their
      older members for problem behaviors, and 4) if departments provided nonclinical
      roles for older anesthesiologists. DESIGN: Survey instrument. SETTING: Academic
      medical centers. MEASUREMENTS: An anonymous, web-based questionnaire that
      included questions on demographics and specific policy-related issues was sent to
      chairpersons of all academic anesthesia departments in the ASA database. MAIN
      RESULTS: No department directly addressed every issue listed in the survey.
      Department size and the number of anesthesiologists over 60 years of age were
      unrelated to whether that department had one or more policies for older
      anesthesiologists. Twenty percent of programs stopped night call at age 60 years.
      Most departments did not exempt older anesthesiologists of any age from call
      responsibilities. Almost all departments tracked critical incidents and errors in
      technique and/or judgment. Almost three quarters tracked substance abuse, and
      over half of the responding departments tracked physical and emotional impairment
      and fixation errors. A third of departments tracked all 6 types of problem
      behavior. Only 12% had specific assessment tools for tracking problem behaviors
      in the clinic, and no department used these tools specifically for older
      anesthesiologists. While only 17% of departments directed older anesthesiologists
      into nonclinical roles, older clinicians had teaching, mentoring, and
      administrative roles within most of the departments. CONCLUSIONS: Relatively few
      departments had specific policies for older anesthesiologists that addressed the
      issues raised in the survey. Further research is needed to determine whether
      departments should decrease ambiguity of their policies, formulate explicit
      policies for older anesthesiologists, especially in regard to call, and assess
      problem behaviors more directly.

PMID- 22617419
TI  - WNTs in synapse formation and neuronal circuitry.
AB  - Wnt proteins play important roles in wiring neural circuits. Wnts regulate many
      aspects of neural circuit generation through their receptors and distinct
      signalling pathways. In this review, we discuss recent findings on the functions
      of Wnts in various aspects of neural circuit formation, including neuronal
      polarity, axon guidance, synapse formation, and synaptic plasticity in vertebrate
      and invertebrate nervous systems.

PMID- 22617420
TI  - Three decades of Wnts: a personal perspective on how a scientific field
      developed.
AB  - Wnt genes and components of Wnt signalling pathways have been implicated in a
      wide spectrum of important biological phenomena, ranging from early organismal
      development to cell behaviours to several diseases, especially cancers. Emergence
      of the field of Wnt signalling can be largely traced back to the discovery of the
      first mammalian Wnt gene in 1982. In this essay, we mark the thirtieth
      anniversary of that discovery by describing some of the critical scientific
      developments that led to the flowering of this field of research.

PMID- 22617421
TI  - Drugging Wnt signalling in cancer.
AB  - Aberrant regulation of the Wnt signalling pathway has emerged as a prevalent
      theme in cancer biology. This chapter summarizes the research that provides a
      proof of concept for inhibiting Wnt signalling in cancer, the potential means by
      which this could be achieved, and some recent advances towards this goal. A brief
      discussion of molecular diagnostics and possible safety concerns is also
      provided.

PMID- 22617423
TI  - HPV-16 E2 contributes to induction of HPV-16 late gene expression by inhibiting
      early polyadenylation.
AB  - We provide evidence that the human papillomavirus (HPV) E2 protein regulates HPV
      late gene expression. High levels of E2 caused a read-through at the early
      polyadenylation signal pAE into the late region of the HPV genome, thereby
      inducing expression of L1 and L2 mRNAs. This is a conserved property of E2 of
      both mucosal and cutaneous HPV types. Induction could be reversed by high levels
      of HPV-16 E1 protein, or by the polyadenylation factor CPSF30. HPV-16 E2
      inhibited polyadenylation in vitro by preventing the assembly of the CPSF
      complex. Both the N-terminal and hinge domains of E2 were required for induction
      of HPV late gene expression in transfected cells as well as for inhibition of
      polyadenylation in vitro. Finally, overexpression of HPV-16 E2 induced late gene
      expression from a full-length genomic clone of HPV-16. We speculate that the
      accumulation of high levels of E2 during the viral life cycle, not only turns off
      the expression of the pro-mitotic viral E6 and E7 genes, but also induces the
      expression of the late HPV genes L1 and L2.

PMID- 22617422
TI  - The many faces and functions of beta-catenin.
AB  - beta-Catenin (Armadillo in Drosophila) is a multitasking and evolutionary
      conserved molecule that in metazoans exerts a crucial role in a multitude of
      developmental and homeostatic processes. More specifically, beta-catenin is an
      integral structural component of cadherin-based adherens junctions, and the key
      nuclear effector of canonical Wnt signalling in the nucleus. Imbalance in the
      structural and signalling properties of beta-catenin often results in disease and
      deregulated growth connected to cancer and metastasis. Intense research into the
      life of beta-catenin has revealed a complex picture. Here, we try to capture the
      state of the art: we try to summarize and make some sense of the processes that
      regulate beta-catenin, as well as the plethora of beta-catenin binding partners.
      One focus will be the interaction of beta-catenin with different transcription
      factors and the potential implications of these interactions for direct cross
      talk between beta-catenin and non-Wnt signalling pathways.

PMID- 22617426
TI  - Transcription: another mark in the tail.
AB  - The C-terminal domain (CTD) of the largest RNA polymerase II (RNAPII) subunit
      undergoes dynamic phosphorylation to support transcription-associated events and
      drive the transcription cycle. In mammalian cells, it comprises 52 repeats of the
      heptapeptide sequence Tyr(1)-Ser(2)-Pro(3)-Thr(4)-Ser(5)-Pro(6)-Ser(7). While
      important functions for Ser(2)-, Ser(5)-, and Ser(7)-phosphorylation have
      previously been described, a new report in The EMBO Journal now suggests an
      unexpectedly crucial role for Thr(4) phosphorylation as well.

PMID- 22617424
TI  - Adult mammalian stem cells: the role of Wnt, Lgr5 and R-spondins.
AB  - After its discovery as oncogen and morphogen, studies on Wnt focused initially on
      its role in animal development. With the finding that the colorectal tumour
      suppressor gene APC is a negative regulator of the Wnt pathway in (colorectal)
      cancer, attention gradually shifted to the study of the role of Wnt signalling in
      the adult. The first indication that adult Wnt signalling controls stem cells
      came from a Tcf4 knockout experiment: mutant mice failed to build crypt stem cell
      compartments. This observation was followed by similar findings in multiple other
      tissues. Recent studies have indicated that Wnt agonists of the R-spondin family
      provide potent growth stimuli for crypts in vivo and in vitro. Independently,
      Lgr5 was found as an exquisite marker for these crypt stem cells. The story has
      come full circle with the finding that the stem cell marker Lgr5 constitutes the
      receptor for R-spondins and occurs in complex with Frizzled/Lrp.

PMID- 22617425
TI  - Mitotic and mitogenic Wnt signalling.
AB  - Canonical Wnt signalling plays an important role in development, tissue
      homeostasis, and cancer. At the cellular level, canonical Wnt signalling acts by
      regulating cell fate, cell growth, and cell proliferation. With regard to
      proliferation, there is increasing evidence for a complex interaction between
      canonical Wnt signalling and the cell cycle. Mitogenic Wnt signalling regulates
      cell proliferation by promoting G1 phase. In mitosis, components of the Wnt
      signalling cascade function directly in spindle formation. Moreover, Wnt
      signalling is strongly activated in mitosis, suggesting that 'mitotic Wnt
      signalling' plays an important role to orchestrate a cell division program. Here,
      we review the complex interplay between Wnt signalling and the cell cycle.

PMID- 22617427
TI  - Interaction between catechol-O-methyltransferase (COMT) Val158Met genotype and
      genetic vulnerability to schizophrenia during explicit processing of aversive
      facial stimuli.
AB  - BACKGROUND: Emotion dysregulation is a key feature of schizophrenia, a brain
      disorder strongly associated with genetic risk and aberrant dopamine signalling.
      Dopamine is inactivated by catechol-O-methyltransferase (COMT), whose gene
      contains a functional polymorphism (COMT Val158Met) associated with differential
      activity of the enzyme and with brain physiology of emotion processing. The aim
      of the present study was to investigate whether genetic risk for schizophrenia
      and COMT Val158Met genotype interact on brain activity during implicit and
      explicit emotion processing. METHOD: A total of 25 patients with schizophrenia,
      23 healthy siblings of patients and 24 comparison subjects genotyped for COMT
      Val158Met underwent functional magnetic resonance imaging during implicit and
      explicit processing of facial stimuli with negative emotional valence. RESULTS:
      We found a main effect of diagnosis in the right amygdala, with decreased
      activity in patients and siblings compared with control subjects. Furthermore, a
      genotype * diagnosis interaction was found in the left middle frontal gyrus, such
      that the effect of genetic risk for schizophrenia was evident in the context of
      the Val/Val genotype only, i.e. the phenotype of reduced activity was present
      especially in Val/Val patients and siblings. Finally, a complete inversion of the
      COMT effect between patients and healthy subjects was found in the left striatum
      during explicit processing. CONCLUSIONS: Overall, these results suggest complex
      interactions between genetically determined dopamine signalling and risk for
      schizophrenia on brain activity in the prefrontal cortex during emotion
      processing. On the other hand, the effects in the striatum may represent state
      related epiphenomena of the disorder itself.

PMID- 22617428
TI  - SL-01, an oral gemcitabine derivative, inhibited human cancer growth more
      potently than gemcitabine.
AB  - SL-01, an oral gemcitabine derivative, was synthesized by introducing the moiety
      of 3-(dodecyloxycarbonyl)pyrazine-2-carbonyl at the N4-position on the cytidine
      ring of gemcitabine. Our goal in this study was to evaluate the efficacy of SL-01
      on the growth of human cancers with gemcitabine as control. Experiments were
      performed on human non-small cell lung cancer NCI-H460 and colon cancer HCT-116
      both in vitro and in vivo. In vitro assays, SL-01 significantly inhibited the
      growth of cancer cells as determined by the 3-[4, 5-dimethylthiazol-2-yl]-2, 5
      diphenyltetrazolium bromide (MTT) assay. Further studies indicated that SL-01
      induced the cancer cells to apoptosis showing chromatin condensation and
      externalization of phosphatidylserine. In in vivo studies, we evaluated the
      efficacy of SL-01 in nude mice bearing human cancer xenografts. SL-01 effectively
      delayed the growth of NCI-H460 and HCT-116 without significant loss of body
      weight. Molecular analysis indicated that the high efficacy of SL-01 was
      associated with its ability to induce apoptosis as evidenced by increase of
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)
      staining cells, activation of caspase-9, caspase-3 and cleaved poly ADP-ribose
      polymerase (PARP) in tumor tissues. SL-01 also increased Bax/Bcl-2 ratio in
      cancer cells. These biological activities of SL-01 were more potential than that
      of gemcitabine. Based on these in vitro and in vivo results, SL-01 is proposed as
      a potent oral anticancer agent that may supplant the use of gemcitabine in the
      clinic.

PMID- 22617429
TI  - Inorganic arsenic represses interleukin-17A expression in human activated Th17
      lymphocytes.
AB  - Trivalent inorganic arsenic [As(III)] is an efficient anticancer agent used to
      treat patients suffering from acute promyelocytic leukemia. Recently,
      experimental studies have clearly demonstrated that this metalloid can also cure
      lymphoproliferative and/or pro-inflammatory syndromes in different murine models
      of chronic immune-mediated diseases. T helper (Th) 1 and Th17 lymphocytes play a
      central role in development of these diseases, in mice and humans, especially by
      secreting the potent pro-inflammatory cytokine interferon-gamma and IL-17A,
      respectively. As(III) impairs basic functions of human T cells but its ability to
      modulate secretion of pro-inflammatory cytokines by differentiated Th lymphocytes
      is unknown. In the present study, we demonstrate that As(III), used at
      concentrations clinically achievable in plasma of patients, has no effect on the
      secretion of interferon-gamma from Th1 cells but almost totally blocks the
      expression and the release of IL-17A from human Th17 lymphocytes co-stimulated
      for five days with anti-CD3 and anti-CD28 antibodies, in the presence of
      differentiating cytokines. In addition, As(III) specifically reduces mRNA levels
      of the retinoic-related orphan receptor (ROR)C gene which encodes RORgammat, a
      key transcription factor controlling optimal IL-17 expression in fully
      differentiated Th17 cells. The metalloid also blocks initial expression of IL-17
      gene induced by the co-stimulation, probably in part by impairing activation of
      the JNK/c-Jun pathway. In conclusion, our results demonstrate that As(III)
      represses expression of the major pro-inflammatory cytokine IL-17A produced by
      human Th17 lymphocytes, thus strengthening the idea that As(III) may be useful to
      treat inflammatory immune-mediated diseases in humans.

PMID- 22617430
TI  - Nonclinical safety strategies for stem cell therapies.
AB  - Recent breakthroughs in stem cell biology, especially the development of the
      induced pluripotent stem cell techniques, have generated tremendous enthusiasm
      and efforts to explore the therapeutic potential of stem cells in regenerative
      medicine. Stem cell therapies are being considered for the treatment of
      degenerative diseases, inflammatory conditions, cancer and repair of damaged
      tissue. The safety of a stem cell therapy depends on many factors including the
      type of cell therapy, the differentiation status and proliferation capacity of
      the cells, the route of administration, the intended clinical location, long term
      survival of the product and/or engraftment, the need for repeated administration,
      the disease to be treated and the age of the population. Understanding the
      product profile of the intended therapy is crucial to the development of the
      nonclinical safety study design.

PMID- 22617431
TI  - Ophiuroid robot that self-organizes periodic and non-periodic arm movements.
AB  - Autonomous decentralized control is a key concept for understanding the mechanism
      underlying adaptive and versatile locomotion of animals. Although the design of
      an autonomous decentralized control system that ensures adaptability by using
      coupled oscillators has been proposed previously, it cannot comprehensively
      reproduce the versatility of animal behaviour. To tackle this problem, we focus
      on using ophiuroids as a simple model that exhibits versatile locomotion
      including periodic and non-periodic arm movements. Our existing model for
      ophiuroid locomotion uses an active rotator model that describes both oscillatory
      and excitatory properties. In this communication, we develop an ophiuroid robot
      to confirm the validity of this proposed model in the real world. We show that
      the robot travels by successfully coordinating periodic and non-periodic arm
      movements in response to external stimuli.

PMID- 22617433
TI  - Morphology and bacterial colonisation of tooth/ceramic restoration interface
      after different cement excess removal techniques.
AB  - OBJECTIVES: To evaluate the influence of different protocols for resin cement
      removal during cementation on biofilm formation. METHODS: Twenty-eight ceramic
      blocks, which were injected under pressure, were placed over enamel blocks
      obtained from freshly extracted bovine incisors. The ceramic blocks were cemented
      to the enamel blocks using a dual-cured resin cement and the excess resin was
      removed according to the experimental group: TS: Teflon spatula; BR: brush; BR+:
      brush and polishing; SB+: scalpel blade and polishing. After autoclaving, the
      samples were colonised by incubation in a sucrose broth suspension standardised
      with Streptococcus mutans in microaerophilic stove. Specimens were quantitatively
      analysed for bacterial adherence at the adhesive interface using confocal laser
      scanning microscopy and counting the colony forming units, and qualitatively
      analysed using SEM. The roughness (Ra/Rz/RSm) was also analysed. Data were
      analysed by 1-way ANOVA and Tukey's test (5%). RESULTS: The roughness values
      ranged from 0.96 to 1.69 MUm for Ra (p>0.05), from 11.59 to 22.80 MUm for Rz
      (p=0.02<0.05) and from 293.2 to 534.3 MUm for RSm (p=0.00). Bacterial adhesion
      varied between 1,974,000 and 2,814,000 CFU/ml (p=0.00). Biofilm mean thickness
      ranged from 0.477 and 0.556 MUm (p>0.05), whilst the biovolume values were
      between 0.388 and 0.547 MUm(3)/MUm(2) (p=0.04). Lower values for roughness,
      bacterial adhesion, biofilm thickness and biovolume were found with BR, whilst TS
      presented the highest values for most of the parameters. SEM images confirmed the
      quantitative values. CONCLUSIONS: The restoration margin morphology and interface
      roughness affects bacterial accumulation. The brush technique promoted less
      bacterial colonisation at the adhesive interface than did the other removal
      methods. CLINICAL SIGNIFICANCE: The brush technique seems to be a good option for
      removing the excess resin cement after adhesive cementation in clinical practice,
      as indicated by its better results with lower bacterial colonisation.

PMID- 22617434
TI  - Development and validation of the Chinese version of the Massachusetts General
      Hospital Acupuncture Sensation Scale: an exploratory and methodological study.
AB  - BACKGROUND: The Massachusetts General Hospital Acupuncture Sensation Scale (MASS)
      is a tool to measure needle sensations. The aims of the present study were to
      develop a Chinese version and to assess its psychometric properties. METHODS:
      This study was a methodological and exploratory study. The English version of the
      MASS was translated into Chinese using standardised translation procedures.
      Content validity was conducted by nine acupuncture experts. The prefinal Chinese
      version (C-MASS) was then administered to 30 acupuncture-naive, healthy subjects.
      Electroacupuncture was performed on the right LI4 and LI11 acupoints for 30 min.
      A test-retest reliability measurement was administered 1-2 weeks later. Construct
      validity was examined by comparing results from C-MASS and the Short-Form McGill
      Pain Questionnaire (SF-MPQ). The construct validity was further assessed by the
      principle component analysis. RESULTS: C-MASS demonstrated a content validity
      ratio on relevance and importance from -0.04 to 1.00. Convergent validity was
      demonstrated by its significant association with the sensory dimension of SF-MPQ
      (gamma=0.63, p<0.05). Discriminant validity was demonstrated by its low
      association with the affective dimension of SF-MPQ (gamma=-0.3, p=0.111). A five
      factor structure of C-MASS was established by factor analysis. C-MASS
      demonstrated good internal consistency (Cronbach's alpha=0.71) and test-retest
      reliability (intraclass correlation coefficient=0.92). Since the descriptor
      'sharp pain' was not a valid needle sensation related to deqi, this was removed
      from C-MASS. We renamed the scale as the Modified MASS-Chinese version (C-MMASS).
      CONCLUSIONS: A 12-descriptor C-MMASS was established and shown to be a reliable
      and valid tool in reporting needle sensations associated with deqi among healthy
      young Chinese people.

PMID- 22617435
TI  - Detection of DNA damage in workers exposed to JP-8 jet fuel.
AB  - The genotoxicity of jet propulsion fuel 8 (JP-8) was assessed in the leukocytes
      of archived blood specimens from U.S. Air Force personnel using the comet assay.
      No differences in mean comet assay measurements were found between low, moderate,
      and high exposure groups before or after a 4h work shift. Before the work shift,
      mean tail DNA and mean tail (Olive) moment increased as the concentration of
      benzene measured in end-exhaled breath increased, indicating that prior
      environmental or work-related exposures to benzene produced DNA damage. The
      number of cells with highly damaged DNA decreased as the pre-shift benzene
      concentration in breath increased. It is not clear why the decrease is occurring.
      Mean tail DNA and mean tail (Olive) moment decreased as the concentrations of
      benzene and naphthalene measured in breath immediately after the work shift
      increased. These inverse relationships may reflect a slower rate of absorption or
      a faster rate of expiration of benzene in the lung. The number of cells with
      highly damaged DNA increased as the concentration of urinary (2
      methoxyethoxy)acetic acid (MEAA) increased. This relationship was not seen in
      urinary MEAA adjusted for creatinine. MEAA is a metabolite of the deicing agent 2
      (2-methoxyethoxy)ethanol contained in JP-8. MEAA or a component of JP-8
      correlated with MEAA may have a toxic effect on DNA.

PMID- 22617437
TI  - The plasma membrane as a control center for autophagy.
AB  - Autophagosomes may derive membrane from diverse sources, including the plasma
      membrane, Golgi, endoplasmic reticulum and mitochondria. The plasma membrane
      contributes membrane to ATG12-ATG5-ATG16L1-positive phagophore precursor vesicles
      (LC3-negative) by both clathrin-dependent and -independent routes. We recently
      observed that ARF6 regulates autophagy and that this could be explained, at least
      in part, by its role in the generation of phosphatidylinositol 4,5-bisphosphate
      [PtdIns(4,5)P 2], which influences endocytic uptake of plasma membrane into
      autophagosome precursors. The subsequent maturation of these small phagophore
      precursors into phagophores (ATG12-ATG5-ATG16L1-positive and LC3-positive), is
      assisted by SNARE-mediated homotypic fusion that increase their size and enhance
      their ability to acquire LC3-II. It appears that a plasma membrane-derived pool
      of VAMP7 is a key mediator of these fusion events. Thus, events at the plasma
      membrane may regulate distinct steps in the biogenesis of phagophores.

PMID- 22617438
TI  - Autophagosome assembly and cargo capture in the distal axon.
AB  - Autophagy is an essential lysosomal degradation pathway in neurons, yet the basic
      mechanisms involved are poorly understood. Here, we discuss our recent study in
      which we define autophagosome dynamics in primary neurons. We find that
      autophagosomes initiate at the distal tip of the axon in primary neurons and
      undergo retrograde transport toward the cell soma. As they move distally to
      proximally along the axon, autophagosomes mature and become increasingly
      acidified, consistent with the formation of an autolysosomal compartment that may
      more effectively catalyze the degradation of enveloped cargo. Our findings
      suggest that autophagosome biogenesis and maturation is a constitutive process in
      primary neurons that is temporally and spatially regulated along the axon.

PMID- 22617439
TI  - BCL2-CISD2: An ER complex at the nexus of autophagy and calcium homeostasis?
AB  - CISD2, an ER BCL2-associated autophagy regulator also known as NAF-1, is
      responsible for the human degenerative disorder Wolfram Syndrome 2. In order to
      interrogate the physiological role of CISD2 we generated and characterized the
      Cisd2 gene deletion in mice. Cisd2 null mice manifest significant degeneration in
      skeletal muscle tissues, which is accompanied with augmented autophagy,
      dysregulated Ca ( 2+)  homeostasis and elongated mitochondria. Our findings
      describe a novel role for BCL2-CISD2 in the homeostatic maintenance of skeletal
      muscle. It remains to be elucidated how and if the antagonism of the BECN1
      autophagy-initiating complex and modulation of ER Ca ( 2+)  homeostasis by BCL2
      CISD2 are interconnected.

PMID- 22617440
TI  - microRNA  30A promotes autophagy in response to cancer therapy.
AB  - microRNAs (miRNAs) are a class of small regulatory RNAs that regulate gene
      expression at the post-transcriptional level. miRNAs play important roles in the
      regulation of development, growth, and metastasis of cancer, and in determining
      the response of tumor cells to anticancer therapy. In recent years, they have
      also emerged as important regulators of autophagy, a lysosomal-mediated pathway
      that contributes to degradation of a cell's own components. Imatinib, a targeted
      competitive inhibitor of the BCR-ABL1 tyrosine kinase, has revolutionized the
      clinical treatment of chronic myelogenous leukemia (CML). We demonstrate that
      MIR30A-mediated autophagy enhances imatinib resistance against CML including
      primary stem and progenitor cells. MIR30A, but not MIR101, is a potent inhibitor
      of autophagy by selectively downregulating BECN1 and ATG5 expression in CML
      cells. MIR30A mimics, as well as knockdown of BECN1 and ATG5, increases intrinsic
      apoptotic pathways. In contrast, the antagomir-30A increases autophagy and
      inhibits intrinsic apoptotic pathways, confirming that autophagy serves to
      protect against apoptosis. Taken together, these data clarify some of the
      underlying molecular mechanisms of tyrosine kinase inhibitor-induced autophagy.

PMID- 22617441
TI  - DISC1 and the aggresome: a disruption to cellular function?
AB  - Disrupted in Schizophrenia 1 (DISC1) is a key susceptibility gene for major
      psychiatric disorders. DISC1 plays a role in key neuronal processes such as
      neuronal proliferation, migration, integration and function via DISC1's roles at
      the centrosome and synapse, and in the regulation of intracellular signaling
      pathways. Recently, the idea of protein aggregation as a disease mechanism for
      DISC1 has been suggested. In our recent paper we explore these DISC1 protein
      aggregates in cell lines and neurons and find they are recruited to the aggresome
      and cause disruption of DISC1 function in intracellular transport.

PMID- 22617442
TI  - Autophagy fuels tissue fibrogenesis.
AB  - Activation of hepatic stellate cells (HSC), a resident pericytic cell in liver,
      into a proliferative and fibrogenic cell type, is the principal event underlying
      hepatic fibrosis following injury. Release of lipid droplets (LD) containing
      retinyl esters and triglyceride is a defining feature of HSC activation, yet the
      basis for this release has remained mysterious. Here we offer a surprising
      discovery that autophagy is the missing link underlying LD release, by
      stimulating metabolism of their contents to provide the energy vital to fuel HSC
      activation. By specifically inhibiting the autophagic pathway in activated HSC,
      LD release is impaired and cellular ATP levels are decreased. Moreover, animals
      with HSC-specific deletion of Atg7 display attenuated activation following liver
      injury, leading to reduced fibrosis in vivo. We further demonstrate that
      fibrogenic cells from other organs, including kidney and lung, also rely on
      autophagy as a core pathway driving the scarring response. Our results provide a
      novel framework for understanding pathways underlying fibrogenic cell responses
      to tissue injury.

PMID- 22617443
TI  - Autophagy contributes to lysosomal storage disorders.
AB  - Degradation in the lysosome/vacuole is not the final step of autophagy. In
      particular, for starvation-induced autophagy it is necessary to release the
      breakdown products back into the cytosol. However, some researchers ignore this
      last step and simply refer to the endpoint of autophagy as degradation, or
      perhaps even cargo delivery. In many cases this is not a serious issue; however,
      the analysis of autophagy's role in certain diseases makes clear that this can be
      a significant error.

PMID- 22617444
TI  - A new role for ATM: regulating mitochondrial function and mitophagy.
AB  - The various pathologies in ataxia telangiectasia (A-T) patients including T-cell
      lymphomagenesis have been attributed to defects in the DNA damage response
      pathway because ATM, the gene mutated in this disease, is a key mediator of this
      process. Analysis of Atm-deficient thymocytes in mice reveals that the absence of
      this gene results in altered mitochondrial homeostasis, a phenomenon that appears
      to result from abnormal mitophagy engagement. Interestingly, allelic loss of the
      autophagic gene Becn1 delays tumorigenesis in Atm-null mice presumably by
      reversing the mitochondrial abnormalities and not by improving the DNA damage
      response (DDR) pathway. Thus, ATM plays a critical role in modulating
      mitochondrial homeostasis perhaps by regulating mitophagy.

PMID- 22617445
TI  - Autophagy plays a critical role in kidney tubule maintenance, aging and ischemia
      reperfusion injury.
AB  - Autophagy is responsible for the degradation of protein aggregates and damaged
      organelles. Several studies have reported increased autophagic activity in
      tubular cells after kidney injury. Here, we examine the role of tubular cell
      autophagy in vivo under both physiological conditions and stress using two
      different tubular-specific Atg5-knockout mouse models. While Atg5 deletion in
      distal tubule cells does not cause a significant alteration in kidney function,
      deleting Atg5 in both distal and proximal tubule cells results in impaired kidney
      function. Already under physiological conditions, Atg5-null tubule cells display
      a significant accumulation of p62 and oxidative stress markers. Strikingly,
      tubular cell Atg5-deficiency dramatically sensitizes the kidneys to ischemic
      injury, resulting in impaired kidney function, accumulation of damaged
      mitochondria as well as increased tubular cell apoptosis and proliferation,
      highlighting the critical role that autophagy plays in maintaining tubular cell
      integrity during stress conditions.

PMID- 22617446
TI  - Lateralization of event-related potential effects during mental rotation of
      polygons.
AB  - Numerous studies have shown that there is an amplitude modulation of the late
      positivity depending on the angular disparity during mental rotation performance.
      However, almost all of these studies used characters as stimulus material,
      whereas studies with different stimuli are rare. In the present experiment, 35
      participants were instructed to rotate polygons mentally. Most importantly, with
      this stimulus material, the well-known event-related potential effects were also
      present at posterior electrode leads. Interestingly, the amplitude modulation
      were found to be larger and more reliable over left than over right posterior
      electrode leads, a finding reported previously for characters as stimuli,
      although not consistently. Thus, the present data suggest that the left
      lateralization of event-related potential effects during mental rotation of
      characters might not be because of their 'verbal nature', but might suggest a
      stronger involvement of the left parietal cortex during mental rotation per se, a
      suggestion that needs to be addressed with methods providing a higher spatial
      resolution.

PMID- 22617447
TI  - MicroRNA-320 induces neurite outgrowth by targeting ARPP-19.
AB  - MicroRNAs are important in the development, functioning, and pathophysiology of
      the central nervous system. Here, we show that increasing the levels of microRNA
      320 (miR-320) for 3 days markedly increases neurite length, and at 4 days,
      reduces the total cell number in Neuro-2A cells. In-silico analysis of possible
      miR-320 targets identified cAMP-regulated phosphoprotein-19 kDa (ARPP-19) and
      semaphorin 3a as potential targets that could be involved. ARPP-19 was validated
      by showing reduced mRNA and protein levels when miR-320 was overexpressed,
      whereas miR-320 had no effect on semaphorin 3a expression. ARPP-19 is known to
      inhibit protein phosphatase-2A activity, which inhibits mitosis and induces
      neurite outgrowth, making this the likely mechanism. Thus, increased levels of
      miR-320 lead to decreased levels of ARPP-19, increased neurite length, and fewer
      total cells. These data suggest that miR-320 could play a role in neuronal
      development and might be a target to enhance neuronal regeneration following
      injury.

PMID- 22617448
TI  - Amygdala-orbitofrontal resting-state functional connectivity is associated with
      trait anger.
AB  - An important distinction in research on the neural mechanisms of emotion
      regulation involves the relatively limited duration of emotional states versus
      emotional traits that are defined as the stable tendency to experience particular
      emotions in daily life. Neuroimaging investigations of the regulation of anger
      states point to the involvement of reciprocal changes in the prefrontal cortex
      and amygdala activity, but the neural substrate of trait anger has received less
      attention. We used resting-state functional MRI to determine whether the
      variation in the strength of functional connectivity between the amygdala and the
      orbitofrontal cortex is associated with trait anger. Sixteen healthy men
      completed the Spielberger State-Trait Anger Expression Inventory. Correlational
      analysis for resting-state functional connectivity (RSFC) was carried out with
      the left and the right amygdala as separate seed regions. Anger measures were
      correlated to RSFC involving the right and the left amygdala on a voxel-by-voxel
      basis across all individuals. We found that Trait Anger was inversely associated
      with the strength of RSFC between the amygdala and the contralateral middle
      orbitofrontal cortex. The association was stronger for the right amygdala-left
      orbitofrontal connection. Anger Control, the tendency to try to control
      expressions of anger, showed the opposite pattern of being positively correlated
      with amygdala-orbitofrontal connectivity. The present study provides evidence
      that RSFC in a corticolimbic circuit might subserve stable differences in anger
      regulation. Our findings also suggest that RSFC may prove valuable as a trait
      marker for disorders characterized by emotional dysregulation such as depression,
      anxiety, and personality disorders.

PMID- 22617449
TI  - Biological activities of lignin hydrolysate-related compounds.
AB  - Lignin hydrolysates contain many different chemical species, including ferulic
      acid, coumaric acid, vanillic acid, vanillin, syringaldehyde and furfural. From
      the perspective of biofuels, these compounds are problematic and can cause
      downstream loss of product if not removed prior to beginning the fermentative
      process. In contrast, a search for these compounds within the literature turns up
      many papers where the same compounds have beneficial properties pertaining to
      human health, including as antioxidants and in cancer prevention, or are involved
      in bacterial cell-to-cell signaling. Consequently, this article reviews the dual
      nature of these and other compounds found in lignin hydrolysates, highlighting
      both their detrimental and beneficial activities.

PMID- 22617450
TI  - Molecular docking study on the alpha3beta2 neuronal nicotinic acetylcholine
      receptor complexed with alpha-conotoxin GIC.
AB  - Nicotinic acetylcholine receptors (nAChRs) are a diverse family of homo- or
      heteropentameric ligand-gated ion channels. Understanding the physiological role
      of each nAChR subtype and the key residues responsible for normal and
      pathological states is important. alpha-Conotoxin neuropeptides are highly
      selective probes capable of discriminating different subtypes of nAChRs. In this
      study, we performed homology modeling to generate the neuronal alpha3, beta2 and
      beta4 subunits using the x-ray structure of the alpha1 subunit as a template. The
      structures of the extracellular domains containing ligand binding sites in the
      alpha3beta2 and alpha3beta4 nAChR subtypes were constructed using MD simulations
      and ligand docking processes in their free and ligand-bound states using alpha
      conotoxin GIC, which exhibited the highest alpha3beta2 vs. alpha3beta4
      discrimination ratio. The results provide a reasonable structural basis for such
      a discriminatory ability, supporting the idea that the present strategy can be
      used for future investigations on nAChR-ligand complexes.

PMID- 22617451
TI  - Effect of interferon-gamma on the fusion of mononuclear osteoclasts into bone
      resorbing osteoclasts.
AB  - Osteoclasts are multinucleated cells that are formed by the fusion of pre-fusion
      osteoclasts (pOCs). The fusion of pOCs is known to be important for osteoclastic
      bone resorption. Here, we examined the effect of IFN-gamma on the fusion of pOCs.
      IFN-gamma greatly increased the fusion of pOCs in a dose-dependent manner.
      Furthermore, IFN-gamma induced pOC fusion even in hydroxyapatite-coated plates
      used as a substitute for bone. The resorption area of pOCs stimulated with IFN
      gamma was significantly higher than that of the control cells. IFN-gamma induced
      the expression of dendritic cell-specific transmembrane protein (DC-STAMP), which
      is responsible for the fusion of pOCs. IFN-gamma enhanced DC-STAMP expression in
      a dose-dependent manner. The mRNA expression of c-Fos and nuclear factor of
      activated T cells (NFAT) c1 was enhanced in the pOCs treated with IFN-gamma.
      Taken together, these results provide a new insight into the novel role of IFN
      gamma on the fusion of pOCs.

PMID- 22617452
TI  - FGF-2 inhibits TNF-alpha mediated apoptosis through upregulation of Bcl2-A1 and
      Bcl-xL in ATDC5 cells.
AB  - FGF-2 is involved in cell survival, proliferation, apoptosis, and angiogenesis in
      a wide variety of cells. FRGRs, PI3K and MAP kinases are well known mediators of
      FGF signaling. Despite its known roles during many developmental processes,
      including osteogenesis, there are few known targets of FGF-2. In the present
      study, we identified Bcl2-A1 and Bcl-xL as two prominent targets involved in
      promoting cell survival. Pretreatment of ATDC5 cells with FGF-2 increased cell
      survival, while siRNAs specific for Bcl2-A1 and Bcl-xL compromised the anti-
      apoptotic effect of FGF-2, sensitized the cells to apoptosis triggered by TNF
      alpha. Chemical inhibition of FGFR, NFkB, and PI3K activity by PD173074,
      pyrrolidine dithiocarbamate, and LY294002 respectively abrogated the FGF-2
      mediated induction of Bcl2-A1 and Bcl-xL expression. Taken together, our data
      demonstrate that a subset of Bcl2 family proteins are the targets of FGF-2
      signaling that promotes the survival of ATDC5 cells.

PMID- 22617453
TI  - Molecular characterization and immunohistochemical localization of a mitogen
      activated protein kinase, Accp38b, from Apis cerana cerana.
AB  - The p38 mitogen-activated protein kinase (MAPK) is involved in various processes,
      including stress responses, development, and differentiation. However, little
      information on p38 MAPK in insects is available. In this study, a p38 MAPK gene,
      Accp38b, was isolated from Apis cerana cerana and characterized. The quantitative
      real-time PCR (Q-PCR) analysis revealed that Accp38b was induced by multiple
      stressors. Notably, the expression of Accp38b was relatively higher in the pupae
      phase than in other developmental phases. During the pupae phase, Accp38b
      expression was higher in the thorax than in the head and abdomen and higher in
      the fat body than in the muscle and midgut. Immunohistochemisty showed
      significant positive staining of Accp38b in sections from the brain, eyes, fat
      body, and midgut of A. cerana cerana. These results suggest that Accp38b may play
      a crucial role in stress responses and have multiple aspects function during
      development.

PMID- 22617454
TI  - High sensitivity of embryonic stem cells to proteasome inhibitors correlates with
      low expression of heat shock protein and decrease of pluripotent cell marker
      expression.
AB  - The ubiquitin-proteasome system is a major proteolytic system for nonlysosomal
      degradation of cellular proteins. Here, we investigated the response of mouse
      embryonic stem (ES) cells under proteotoxic stress. Proteasome inhibitors induced
      expression of heat shock protein 70 (HSP70) in a concentration- and time
      dependent manner, and also induced apoptosis of ES cells. Importantly, more
      apoptotic cells were observed in ES cells compared with other somatic cells. To
      understand this phenomenon, we further investigated the expression of HSP70 and
      pluripotent cell markers. HSP70 expression was more significantly increased in
      somatic cells than in ES cells, and expression levels of pluripotent cell markers
      such as Oct4 and Nanog were decreased in ES cells. These results suggest that
      higher sensitivity of ES cells to proteotoxic stress may be related with lower
      capacity of HSP70 expression and decreased pluripotent cell marker expression,
      which is essential for the survival of ES cells.

PMID- 22617455
TI  - Replication of genome-wide association studies on asthma and allergic diseases in
      Korean adult population.
AB  - Allergic diseases such as asthma, allergic rhinitis, and atopic dermatitis are
      heterogeneous diseases characterized by multiple symptoms and phenotypes. Recent
      advancements in genetic study enabled us to identify disease associated genetic
      factors. Numerous genome-wide association studies (GWAS) have revealed multiple
      associated loci for allergic diseases. However, the majority of previous studies
      have been conducted in populations of European ancestry. Moreover, the
      associations of single nucleotide polymorphisms (SNPs) with allergic diseases
      have not been studied amongst the large-scale general Korean population. Herein,
      we performed the replication study to validate the previous variants, known to be
      associated with allergic diseases, in the Korean population. In this study, we
      categorized three allergic related phenotypes, one allergy and two asthma related
      phenotypes, based on self-reports of physician diagnosis and their symptoms from
      8,842 samples. As a result, we found nominally significant associations of 6 SNPs
      with at least one allergic related phenotype in the Korean population.

PMID- 22617456
TI  - Sulforaphane inhibits the Th2 immune response in ovalbumin-induced asthma.
AB  - Sulforaphane (1-isothiocyanato-4-(methylsulfinyl)-butane), belonging to a family
      of natural compounds that are abundant in broccoli, has received significant
      therapeutic interest in recent years. However, the molecular basis of its effects
      remains to be elucidated. In this study, we attempt to determine whether
      sulforaphane regulates the inflammatory response in an ovalbumin (OVA)-induced
      murine asthma model. Mice were sensitized with OVA, treated with sulforaphane,
      and then challenged with OVA. Sulforaphane administration significantly
      alleviated the OVA-induced airway hyperresponsiveness to inhaled methacholine.
      Additionally, sulforaphane suppressed the increase in the levels of SOCS-3 and
      GATA-3 and IL-4 expression in the OVA-challenged mice. Collectively, our results
      demonstrate that sulforaphane regulates Th2 immune responses. This sutdy provides
      novel insights into the regulatory role of sulforaphane in allergen-induced Th2
      inflammation and airway responses, which indicates its therapeutic potential for
      asthma and other allergic diseases.

PMID- 22617457
TI  - Protein phosphorylation on tyrosine restores expression and glycosylation of
      cyclooxygenase-2 by 2-deoxy-D-glucose-caused endoplasmic reticulum stress in
      rabbit articular chondrocyte.
AB  - 2-deoxy-D-glucose(2DG)-caused endoplasmic reticulum (ER) stress inhibits protein
      phosphorylation at tyrosine residues. However, the accurate regulatory
      mechanisms, which determine the inflammatory response of chondrocytes to ER
      stress via protein tyrosine phosphorylation, have not been systematically
      evaluated. Thus, in this study, we examined whether protein phosphorylation at
      tyrosine residues can modulate the expression and glycosylation of COX-2, which
      is reduced by 2DG-induced ER stress. We observed that protein tyrosine
      phosphatase (PTP) inhibitors, sodium orthovanadate (SOV), and phenylarsine oxide
      (PAO) significantly decreased expression of ER stress inducible proteins, glucose
      regulated protein 94 (GRP94), and CCAAT/enhancer-binding-protein- related gene
      (GADD153), which was induced by 2DG. In addition, we demonstrated that SOV and
      PAO noticeably restored the expression and glycosylation of COX-2 after treatment
      with 2DG. These results suggest that protein phosphorylation of tyrosine residues
      plays an important role in the regulation of expression and glycosylation during
      2DG-induced ER stress in rabbit articular chondrocytes.

PMID- 22617458
TI  - Growth of the developing mouse heart: an interactive qualitative and quantitative
      3D atlas.
AB  - Analysis of experiments aimed at understanding the genetic mechanisms of
      differentiation and growth of the heart, calls for detailed insights into cardiac
      growth and proliferation rate of myocytes and their precursors. Such insights in
      mouse heart development are currently lacking. We quantitatively assessed the 3D
      patterns of proliferation in the forming mouse heart and in the adjacent
      splanchnic mesoderm, from the onset of heart formation till the developed heart
      at late gestation. These results are presented in an interactive portable
      document format (Suppl. PDF) to facilitate communication and understanding. We
      show that the mouse splanchnic mesoderm is highly proliferative, and that the
      proliferation rate drops upon recruitment of cells into the cardiac lineage.
      Concomitantly, the proliferation rate locally increases at the sites of chamber
      formation, generating a regionalized proliferation pattern. Quantitative analysis
      shows a gradual decrease in proliferation rate of the ventricular walls with
      progression of development, and a base-to-top decline in proliferation rate in
      the trabecules. Our data offers clear insights into the growth and morphogenesis
      of the mouse heart and shows that in early development the phases of tube
      formation and chamber formation overlap. The resulting interactive quantitative
      3D atlas of cardiac growth and morphogenesis provides a resource for
      interpretation of mechanistic studies.

PMID- 22617460
TI  - Plasma total antioxidant capacity is associated with dietary intake and plasma
      level of antioxidants in postmenopausal women.
AB  - Increased plasma total antioxidant capacity (TAC) has been associated with a high
      consumption of fruits and vegetables. However, limited information is available
      on whether plasma TAC reflects the dietary intake of antioxidants and the levels
      of individual antioxidants in plasma. By using three different assays, the study
      aimed to determine if plasma TAC can effectively predict dietary intake of
      antioxidants and plasma antioxidant status. Forty overweight and apparently
      healthy postmenopausal women were recruited. Seven-day food records and 12-h
      fasting blood samples were collected for dietary and plasma antioxidant
      assessments. Plasma TAC was determined by vitamin C equivalent antioxidant
      capacity (VCEAC), ferric-reducing ability of plasma (FRAP) and oxygen radical
      absorbance capacity (ORAC) assays. TAC values determined by VCEAC were highly
      correlated with FRAP (r=0.79, P<.01) and moderately correlated with ORAC (r=0.34,
      P<.05). Pearson correlation analyses showed that plasma TAC values by VCEAC and
      ORAC had positive correlation with plasma uric acid (r=0.56 for VCEAC; r=0.49 for
      ORAC) and total phenolics (r=0.63 for VCEAC; r=0.36 for ORAC). However, TAC
      measured by FRAP was correlated only with uric acid (r=0.69). After multivariate
      adjustment, plasma TAC determined by VCEAC was positively associated with dietary
      intakes of gamma-tocopherol (P<.001), beta-carotene (P<.05), anthocyanidins
      (P<.05), flavones (P<.05), proanthocyanidins (P<.01) and TAC (P<.05), as well as
      with plasma total phenolics (P<.05), alpha-tocopherol (P<.001), beta
      cryptoxanthin (P<.05) and uric acid (P<.05). The findings indicate that plasma
      TAC measured by VCEAC reflects both dietary and plasma antioxidants and
      represents more closely the plasma antioxidant levels than ORAC and FRAP.

PMID- 22617461
TI  - 'The risks of playing it safe': a prospective longitudinal study of response to
      reward in the adolescent offspring of depressed parents.
AB  - BACKGROUND: Alterations in reward processing may represent an early vulnerability
      factor for the development of depressive disorder. Depression in adults is
      associated with reward hyposensitivity and diminished reward seeking may also be
      a feature of depression in children and adolescents. We examined the role of
      reward responding in predicting depressive symptoms, functional impairment and
      new-onset depressive disorder over time in the adolescent offspring of depressed
      parents. In addition, we examined group differences in reward responding between
      currently depressed adolescents, psychiatric and healthy controls, and also cross
      sectional associations between reward responding and measures of positive
      social/environmental functioning. Method We conducted a 1-year longitudinal study
      of adolescents at familial risk for depression (n = 197; age range 10-18 years).
      Reward responding and self-reported social/environmental functioning were
      assessed at baseline. Clinical interviews determined diagnostic status at
      baseline and at follow-up. Reports of depressive symptoms and functional
      impairment were also obtained. RESULTS: Low reward seeking predicted depressive
      symptoms and new-onset depressive disorder at the 1-year follow-up in individuals
      free from depressive disorder at baseline, independently of baseline depressive
      symptoms. Reduced reward seeking also predicted functional impairment.
      Adolescents with current depressive disorder were less reward seeking (i.e. bet
      less at favourable odds) than adolescents free from psychopathology and those
      with externalizing disorders. Reward seeking showed positive associations with
      social and environmental functioning (extra-curricular activities, humour,
      friendships) and was negatively associated with anhedonia. There were no group
      differences in impulsivity, decision making or psychomotor slowing. CONCLUSIONS:
      Reward seeking predicts depression severity and onset in adolescents at elevated
      risk of depression. Adaptive reward responses may be amenable to change through
      modification of existing preventive psychological interventions.

PMID- 22617459
TI  - Early alcohol exposure disrupts visual cortex plasticity in mice.
AB  - There is growing evidence that deficits in neuronal plasticity underlie the
      cognitive problems seen in fetal alcohol spectrum disorders (FASD). However, the
      mechanisms behind these deficits are not clear. Here we test the effects of early
      alcohol exposure on ocular dominance plasticity (ODP) in mice and the
      reversibility of these effects by phosphodiesterase (PDE) inhibitors. Mouse pups
      were exposed to 5 g/kg of 25% ethanol i.p. on postnatal days (P) 5, 7 and 9. This
      type of alcohol exposure mimics binge drinking during the third trimester
      equivalent of human gestation. To assess ocular dominance plasticity animals were
      monocularly deprived at P21 for 10 days, and tested using optical imaging of
      intrinsic signals. During the period of monocular deprivation animals were
      treated with vinpocetine (20mg/kg; PDE1 inhibitor), rolipram (1.25mg/kg; PDE4
      inhibitor), vardenafil (3mg/kg; PDE5 inhibitor) or vehicle solution. Monocular
      deprivation resulted in the expected shift in ocular dominance of the binocular
      zone in saline controls but not in the ethanol group. While vinpocetine
      successfully restored ODP in the ethanol group, rolipram and vardenafil did not.
      However, when rolipram and vardenafil were given simultaneously ODP was restored.
      PDE4 and PDE5 are specific to cAMP and cGMP respectively, while PDE1 acts on both
      of these nucleotides. Our findings suggest that the combined activation of the
      cAMP and cGMP cascades may be a good approach to improve neuronal plasticity in
      FASD models.

PMID- 22617462
TI  - Drug poisoning deaths in the United States, 1980-2008.
AB  - In 2008, the number of poisoning deaths exceeded the number of motor vehicle
      traffic deaths and was the leading cause of injury death for the fi rst time
      since at least 1980. During the past three decades, the poisoning death rate
      nearly tripled, while the motor vehicle traffic death rate decreased by one-half.
      During this period, the percentage of poisoning deaths that were caused by drugs
      increased from about 60% to about 90%. The population groups with the highest
      drug poisoning death rates in 2008 were males, people aged 45-54 years, and non
      Hispanic white and American Indian or Alaska Native persons. The vast majority of
      drug poisoning deaths are unintentional (see Appendix table). Opioid analgesics
      were involved in more drug poisoning deaths than other specified drugs, including
      heroin and cocaine. Opioid analgesics were involved in nearly 15,000 deaths in
      2008, while cocaine was involved in about 5,100 deaths and heroin was involved in
      about 3,000 deaths (data not shown). Deaths involving opioid analgesics may
      involve other drugs as well, including benzodiazepines (2). In addition to an
      increase in the number of deaths caused by drug poisoning, increases in drug use,
      abuse, misuse, and nonfatal health outcomes have been observed. In the past two
      decades, there has been an increase in the distribution and medical use of
      prescription drugs, including opioid analgesics (3). From 1999 to 2008, the use
      of prescription medications increased (4). In 2007-2008, 48% of Americans used at
      least one prescription drug in the past month and 11% of Americans used five or
      more prescriptions in the past month. Analgesics for pain relief were among the
      common drugs taken by adults aged 20-59 years (4). In 2009-2010, over 5 million
      Americans reported using prescription pain relievers nonmedically in the past
      month (that is, without a doctor's prescription or only for the experience or
      feeling they caused), and the majority of people using prescription pain
      relievers nonmedically reported getting the drugs from friends or family (5,6).
      From 2004 to 2008, the estimated rate of emergency department visits involving
      nonmedical use of opioid analgesics doubled from 49 per 100,000 to 101 per
      100,000 (7). Government agencies and other organizations joined together to
      achieve great reductions in the number of deaths from motor vehicle crashes in
      the past three decades (8,9). A comprehensive approach, including improvements in
      the safety of vehicles; improvements in roadways; increased use of restraint
      systems, such as seat belts and child safety seats; reductions in speed; and also
      efforts to reduce driving under the influence of alcohol and drugs, contributed
      to the decline in motor vehicle related deaths (8,9). Using a comprehensive,
      multifaceted approach, it may be possible to reverse the trend in drug poisoning
      mortality.

PMID- 22617463
TI  - Switching to 3D.

PMID- 22617469
TI  - Preventing WNT signalling.

PMID- 22617472
TI  - Medical waste management at the Oncology Institute of Vojvodina: possibilities of
      successful implementation of medical waste regulation in Serbia.
AB  - Implementation of National waste management strategy, which included most of
      Healthcare facilities (HCF) in Serbia, began in 2009. The present study aimed to
      evaluate the medical waste management strategy protocol at Oncology Institute of
      Vojvodina, which is the first institution in Vojvodina and one of the first
      institutions in Serbia which has implemented the recomended medical waste
      management protocol. Segregation, storage, transportation and treatment were all
      evaluated and that was all performed according to National strategy. Biohazard
      generation rate was 0,17 kg/bed/day, which correspods with values in the HCF in
      Eastern Europe. The results show that the methods for safe management of medical
      waste are acceptable, affordable, and economically justifable to accomplish the
      reduction in the financial costs in HCF business, and can serve as representative
      of proper medical waste management practice for other HCF.

PMID- 22617470
TI  - Specialized ribosomes: a new frontier in gene regulation and organismal biology.
AB  - Historically, the ribosome has been viewed as a complex ribozyme with
      constitutive rather than intrinsic regulatory capacity in mRNA translation.
      However, emerging studies reveal that ribosome activity may be highly regulated.
      Heterogeneity in ribosome composition resulting from differential expression and
      post-translational modifications of ribosomal proteins, ribosomal RNA (rRNA)
      diversity and the activity of ribosome-associated factors may generate
      'specialized ribosomes' that have a substantial impact on how the genomic
      template is translated into functional proteins. Moreover, constitutive
      components of the ribosome may also exert more specialized activities by virtue
      of their interactions with specific mRNA regulatory elements such as internal
      ribosome entry sites (IRESs) or upstream open reading frames (uORFs). Here we
      discuss the hypothesis that intrinsic regulation by the ribosome acts to
      selectively translate subsets of mRNAs harbouring unique cis-regulatory elements,
      thereby introducing an additional level of regulation in gene expression and the
      life of an organism.

PMID- 22617473
TI  - A performance-based method for calculating the design thickness of compacted clay
      liners exposed to high strength leachate under simulated landfill conditions.
AB  - Compacted clay liners (CCLs) when feasible, are preferred to composite
      geosynthetic liners. The thickness of CCLs is typically prescribed by each
      country's environmental protection regulations. However, considering the fact
      that construction of CCLs represents a significant portion of overall landfill
      construction costs; a performance based design of liner thickness would be
      preferable to 'one size fits all' prescriptive standards. In this study
      researchers analyzed the hydraulic behaviour of a compacted clayey soil in three
      laboratory pilot scale columns exposed to high strength leachate under simulated
      landfill conditions. The temperature of the simulated CCL at the surface was
      maintained at 40 +/- 2  degrees C and a vertical pressure of 250 kPa was applied
      to the soil through a gravel layer on top of the 50 cm thick CCL where high
      strength fresh leachate was circulated at heads of 15 and 30 cm simulating the
      flow over the CCL. Inverse modelling using HYDRUS-1D indicated that the hydraulic
      conductivity after 180 days was decreased about three orders of magnitude in
      comparison with the values measured prior to the experiment. A number of
      scenarios of different leachate heads and persistence time were considered and
      saturation depth of the CCL was predicted through modelling. Under a typical
      leachate head of 30 cm, the saturation depth was predicted to be less than 60 cm
      for a persistence time of 3 years. This approach can be generalized to estimate
      an effective thickness of a CCL instead of using prescribed values, which may be
      conservatively overdesigned and thus unduly costly.

PMID- 22617474
TI  - Absolute quantum yield measurement of powder samples.
AB  - Measurement of fluorescence quantum yield has become an important tool in the
      search for new solutions in the development, evaluation, quality control and
      research of illumination, AV equipment, organic EL material, films, filters and
      fluorescent probes for bio-industry. Quantum yield is calculated as the ratio of
      the number of photons absorbed, to the number of photons emitted by a material.
      The higher the quantum yield, the better the efficiency of the fluorescent
      material. For the measurements featured in this video, we will use the Hitachi F
      7000 fluorescence spectrophotometer equipped with the Quantum Yield measuring
      accessory and Report Generator program. All the information provided applies to
      this system. Measurement of quantum yield in powder samples is performed
      following these steps: 1. Generation of instrument correction factors for the
      excitation and emission monochromators. This is an important requirement for the
      correct measurement of quantum yield. It has been performed in advance for the
      full measurement range of the instrument and will not be shown in this video due
      to time limitations. 2. Measurement of integrating sphere correction factors. The
      purpose of this step is to take into consideration reflectivity characteristics
      of the integrating sphere used for the measurements. 3. Reference and Sample
      measurement using direct excitation and indirect excitation. 4. Quantum Yield
      calculation using Direct and Indirect excitation. Direct excitation is when the
      sample is facing directly the excitation beam, which would be the normal
      measurement setup. However, because we use an integrating sphere, a portion of
      the emitted photons resulting from the sample fluorescence are reflected by the
      integrating sphere and will re-excite the sample, so we need to take into
      consideration indirect excitation. This is accomplished by measuring the sample
      placed in the port facing the emission monochromator, calculating indirect
      quantum yield and correcting the direct quantum yield calculation. 5. Corrected
      quantum yield calculation. 6. Chromaticity coordinates calculation using Report
      Generator program. The Hitachi F-7000 Quantum Yield Measurement System offer
      advantages for this application, as follows: High sensitivity (S/N ratio 800 or
      better RMS). Signal is the Raman band of water measured under the following
      conditions: Ex wavelength 350 nm, band pass Ex and Em 5 nm, response 2 sec),
      noise is measured at the maximum of the Raman peak. High sensitivity allows
      measurement of samples even with low quantum yield. Using this system we have
      measured quantum yields as low as 0.1 for a sample of salicylic acid and as high
      as 0.8 for a sample of magnesium tungstate. Highly accurate measurement with a
      dynamic range of 6 orders of magnitude allows for measurements of both sharp
      scattering peaks with high intensity, as well as broad fluorescence peaks of low
      intensity under the same conditions. High measuring throughput and reduced light
      exposure to the sample, due to a high scanning speed of up to 60,000 nm/minute
      and automatic shutter function. Measurement of quantum yield over a wide
      wavelength range from 240 to 800 nm. Accurate quantum yield measurements are the
      result of collecting instrument spectral response and integrating sphere
      correction factors before measuring the sample. Large selection of calculated
      parameters provided by dedicated and easy to use software. During this video we
      will measure sodium salicylate in powder form which is known to have a quantum
      yield value of 0.4 to 0.5.

PMID- 22617471
TI  - Regulation of glucose transport by insulin: traffic control of GLUT4.
AB  - Despite daily fasting and feeding, plasma glucose levels are normally maintained
      within a narrow range owing to the hormones insulin and glucagon. Insulin
      increases glucose uptake into fat and muscle cells through the regulated
      trafficking of vesicles that contain glucose transporter type 4 (GLUT4). New
      insights into insulin signalling reveal that phosphorylation events initiated by
      the insulin receptor regulate key GLUT4 trafficking proteins, including small
      GTPases, tethering complexes and the vesicle fusion machinery. These proteins, in
      turn, control GLUT4 movement through the endosomal system, formation and
      retention of specialized GLUT4 storage vesicles and targeted exocytosis of these
      vesicles. Understanding these processes may help to explain the development of
      insulin resistance in type 2 diabetes and provide new potential therapeutic
      targets.

PMID- 22617475
TI  - Multilocus estimation of selfing and its heritability.
AB  - We describe a new method of estimating the selfing rate (S) in a mixed mating
      population based on a population structure approach that accounts for possible
      intergenerational correlation in selfing rate, giving rise to an estimate of the
      upper limit for heritability of selfing rate (h2). A correlation between
      generations in selfing rate is shown to affect one- and two-locus probabilities
      of identity by descent. Conventional estimates of selfing rate based on a
      population structure approach are positively biased by intergenerational
      correlation in selfing. Multilocus genotypes of individuals are used to give
      maximum-likelihood estimates of S and h2 in the presence of scoring artifacts.
      Our multilocus estimation of selfing rate and its heritability (MESH) method was
      tested with simulated data for a range of conditions. Selfing rate estimates from
      MESH have low bias and root mean squared error, whereas estimates of the
      heritability of selfing rate have more uncertainty. Increasing the number of
      individuals in a sample helps to reduce bias and root mean squared error more
      than increasing the number of loci of sampled individuals. Improved estimates of
      selfing rate, as well as estimates of its heritability, can be obtained with this
      method, although a large number of loci and individuals are needed to achieve
      best results.

PMID- 22617476
TI  - Fertility-preserving treatment in young patients with placental site
      trophoblastic tumors.
AB  - OBJECTIVE: To investigate the methods of fertility-sparing therapy for patients
      with placental site trophoblastic tumor (PSTT) and analyze the outcomes. METHODS:
      From January 1999 to October 2010, the clinical features, pathology, diagnosis,
      fertility-preserving treatment, and outcomes of 6 patients with PSTT were studied
      retrospectively. Six patients were provided with multimodality treatment, which
      combined with surgery and chemotherapy. Five patients had received intrauterine
      arterial infusion chemotherapy. Three patients with polypoid-type tumor were
      treated by dilation and curettage and combination chemotherapy. Three patients
      with nodular masses underwent uterine tumor resection and combination
      chemotherapy. Two patients with nodular masses were treated by combination
      chemotherapy after dilation and curettage, and then uterine tumor resection was
      performed. RESULTS: After follow-up for 10 to 104 months (mean, 47 months), 6
      patients achieved a complete remission, presented no signs of recurrence, and had
      restored normal menstruation. One of them had a normal delivery in July 2011.
      CONCLUSIONS: Fertility-conserving therapy for young women with PSTT would be
      practicable if the patient is younger than 35 years, strongly desires to preserve
      fertility and responds well to chemotherapy and conservative surgery, the
      pathological results of which do not show poor prognostic factors and the gross
      pathologic type does not present markedly enlarged uterus, diffuse infiltrative
      and diffuse multifocal disease within the uterus.

PMID- 22617477
TI  - Pelvic exenterations for gynecological malignancies: a study of 36 cases.
AB  - OBJECTIVE: Evaluation of surgical outcomes, survival, and morbidity associated
      with pelvic exenteration (PE) performed for gynecologic malignancies. METHODS:
      Review of 36 consecutive patients who underwent PE between June 1999 and April
      2010. RESULTS: Pelvic exenteration was performed for cancer of the cervix (n =
      18), endometrium (n = 9), vagina/vulva (n = 8), and ovary (n = 1). Four patients
      underwent PE as primary treatment and 32 patients for recurrent disease after
      pelvic radiotherapy. Median age was 57 years (range, 35-81 years). Bricker (n =
      17), Mainz pouch (n = 10), and augmentation after bladder resection (n = 6) were
      used as urinary derivations. J-pouch coloanal anastomosis was performed in 14,
      colostomy in 13, and side-to-end anastomosis in 4 patients. There was no
      operative mortality. The most important postoperative complications were
      rectovaginal fistula (5), urinary leakage (2), vesicovaginal fistula (1), and
      sepsis (3). One of the 6 patients with a partial cystectomy developed a
      vesicovaginal fistula, which was successfully treated with a Martius flap. With a
      median follow-up of 78 months (range, 2-131) months, the 5-year overall and
      disease-specific survival (DSS) rates were 44% and 52%, respectively. Five-year
      DSS for cervical, endometrial, and vaginal/vulvar cancer was 44%, 80%, and 57%,
      respectively. Combined operative and radiotherapeutic treatment (CORT) was
      performed in 3 patients with pelvic side wall relapse. Of the 15 patients 65
      years or older, a 5-year DSS of 71% was observed in comparison with 42% in the
      younger subgroup, and their complication rates were similar to the younger
      patient group. Thirteen patients (36%) reported to have psychological
      disturbances associated with stoma-related problems. Only 3 patients requested a
      vaginal reconstruction during follow-up. CONCLUSIONS: Pelvic exenteration offers
      a sustained survival with an acceptable morbidity in patients with advanced or
      recurrent gynecologic cancer. Older age was not associated with higher
      morbidity/mortality in this series.

PMID- 22617478
TI  - Early invasive cervical cancer during pregnancy: different therapeutic options to
      preserve fertility.
AB  - INTRODUCTION: Cervical cancer is the second most common cancer diagnosed during
      pregnancy. Conservative management is possible, and different options should be
      discussed with patients. The main decision parameters are stage of disease, lymph
      node status, trimester of pregnancy and wishes of the patient. We reviewed our
      experience on cases of early-stage cervical cancer discovered during pregnancy
      and treated with different options of fertility-sparing management. MATERIALS AND
      METHODS: Between 1990 and 2010, 5 patients with early-stage cervical cancer
      diagnosed during pregnancy were referred to our department for fertility-sparing
      treatment. The mean age at diagnosis was 28.6 years (range, 26-30 years). The
      stages of the tumors according to the International Federation of Gynecology and
      Obstetrics were IA2 in 2 women and IB1 in 3 women. The histological type was
      squamous carcinoma in 3 cases and adenocarcinoma in 2 cases. All patients willing
      to preserve their fertility were treated with vaginal radical trachelectomy (VRT)
      and pelvic lymph nodes dissection (PLN-D). RESULTS: Three procedures were
      performed in the first trimester: 1 patient was treated with medical abortion and
      then VRT and PLN-D, 2 patients were submitted to VRT and PLN-D during the first
      trimester, and 1 patient's case was complicated by spontaneous abortion. One
      patient was observed during the second trimester (20 weeks of gestation) and
      treated with VRT and PLN-D during pregnancy. Because this patient had pelvic
      lymph nodes positive for cancer, a cesarean delivery (CD) with radical
      hysterectomy and para-aortic lymph nodes dissection was performed followed by
      chemoradiotherapy. The last patient was evaluated during the third trimester of
      her pregnancy. Treatment included CD followed by VRT and PLN-D, which was
      delayed, to allow fetal maturity. CONCLUSIONS: Diagnosis of cervical cancer can
      occur during pregnancy. Different options of fertility-sparing treatment can be
      discussed on the basis of several factors: tumor stage, gestational age, and the
      patient's desire regarding fertility and pregnancy sparing.

PMID- 22617479
TI  - Integration of hybrid single-photon emission computed tomography/computed
      tomography in the preoperative assessment of sentinel node in patients with
      cervical and endometrial cancer: our experience and literature review.
AB  - OBJECTIVE: The purpose of this study was to assess whether there is an additional
      value of single-photon emission computed tomography/computed tomography
      (SPECT/CT) over lymphoscintigraphy (LSG) alone for sentinel node (SN) mapping in
      endometrial and cervical cancer. METHODS: Ten women with clinically cervical
      stage IA2 to stage IB1 and 25 women with stage I endometrial cancer underwent
      preoperative LSG for SN mapping. Technetium Tc 99m albumin nanocolloid was
      injected submucosally at 4 points of the cervix. Patients underwent SPECT/CT
      emission-transmission study at least 3 hours after standard planar images.
      Methylene blue was injected into the cervix just before surgery under general
      anesthesia. All patients underwent hysterectomy, bilateral salpingo-oophorectomy,
      and radical regional nodal dissection. Hot and/or blue nodes were labeled as SNs.
      RESULTS: Conventional planar imaging detection rate was 50%, whereas the
      detection rate of at least one SN with SPECT/CT was 91% (32/35); bilateral
      detection was achieved in 7 (39%) of 18 women in planar and in 17 (53%) of 32
      women in SPECT/CT imaging, respectively. Bilateral detection was achieved in 57%
      of women (20/35). Sentinel nodes were located in external and internal iliac
      nodes (66%), obturator nodes (5%), internal iliac nodes (11%), common iliac nodes
      (9%), and presacral nodes (9%). Lymph node involvement was identified in 5
      patients (14%). Sentinel node correctly predicted lymph node involvement in all
      node-positive patients. Sentinel node sensitivity and negative predictive value
      of SPECT/CT were 100%. CONCLUSIONS: Single photon emission computed
      tomography/computed tomography seems to improve intraoperative identification of
      SNs and provides additional useful information about the anatomic location of SNs
      compared to planar LSG in cervical and endometrial cancer.

PMID- 22617480
TI  - Postrecurrent oncologic outcome of patients with ovarian clear cell carcinoma.
AB  - OBJECTIVES: To estimate the long-term clinical outcome of patients with recurrent
      clear cell carcinoma (RCCC) of the ovary in comparison with those with recurrent
      serous adenocarcinoma (RSAC). PATIENTS AND METHODS: In this study, 113 patients
      with RCCC and 365 patients with RSAC were analyzed. The pathological slides were
      evaluated under central pathological review. End points were the overall survival
      (OS), postrecurrence survival (PRS), and timing of death of mortality cases.
      RESULTS: The 5-year OS and PRS rates of patients with RCCC were 22.5 and 13.2%,
      respectively. In both OS and PRS, the prognosis of patients with RCCC was
      significantly poorer than that of the patients with RSAC (OS: P = 0.0007; PRS: P
      < 0.0001). Moreover, regardless of the status of the residual tumor (RT) at the
      initial surgery, the OS and PRS of the patients with RCCC were markedly shorter
      than those with RSAC (RT [-]: OS, P = 0.0005: PRS, P = 0.0002: RT [+]: OS, P <
      0.0001: PRS, P < 0.0001). In multivariable analysis, the histological type was a
      significantly poorer prognostic indicator for OS and PRS (OS [RCCC vs RSAC]:
      hazard ratio, 2.302: 95% confidence interval, 1.723-3.076; P < 0.0001: PRS [RCCC
      vs RSAC]; hazard ratio, 2.353: 95% confidence interval, 1.756-3.155; P < 0.0001).
      Even in the deceased patients (n = 350), the rate of patients with RCCC dying
      within 12 months of recurrence was higher than that of RSAC (RCCC, 67.8%; RSAC,
      40.7%; [P < 0.0001]). CONCLUSIONS: The long-term clinical outcome of patients
      with RCCC was extremely poor. We confirmed that RCCC should be investigated as a
      different malignancy compared with RSAC.

PMID- 22617481
TI  - Tumor-infiltrating dendritic cells may be used as clinicopathologic prognostic
      factors in endometrial carcinoma.
AB  - OBJECTIVE: To investigate the distribution of dendritic cells (DCs) at different
      development status in endometrial carcinoma and their relationship with clinical
      pathology. METHODS: Samples were collected from 95 patients with endometrial
      endometrioid adenocarcinoma treated in Peking University People's Hospital from
      2002 to 2010. Normal endometrial tissue was obtained from 40 women and served as
      controls. Immunohistochemistry was used to detect the expression of S100-, human
      leukocyte antigen (HLA)-DR-, and CD1a-positive DCs within the tumor glandular
      epithelium, the surrounding tumor interstitial tissue, and the equivalent normal
      endometrial tissue. The relationship of these DCs with clinical stage, pathology
      grade, myometrial invasion, and lymph node metastasis was analyzed. RESULTS: The
      rate of S100-positive DCs in the endometrial endometrioid adenocarcinoma
      glandular epithelium samples from the 95 patients was 48.4% (46/95), and that of
      the HLA-DR-positive DCs was 27.4% (26/95), which were both significantly higher
      (P < 0.05) than that in the control group. CD1a-positive DC was rarely expressed
      in endometrial endometrioid adenocarcinoma glandular epithelium. The rates of the
      S100- and HLA-DR-positive DCs in tumor interstitial tissue were similar to that
      of the control group (both, P > 0.05). The proportion of invasion of the S100-
      and HLA-DR-positive DCs was negatively correlated with the clinical stage and
      lymph node metastasis but was not correlated with the pathological grade and
      myometrial invasion. CONCLUSIONS: Dendritic cell invasion was detected in
      endometrial endometrioid adenocarcinoma. S100- and HLA-DR-positive DCs may have
      functions related to the delay of tumor progression and lymph node metastasis.

PMID- 22617482
TI  - Proceedings of the 2012 Rheumatology Winter Clinical Symposia.
AB  - Recent years have witnessed important developments in rheumatology. Novel
      diagnostic methods, stratification approaches, and treatment paradigms have been
      brought into the clinic for a number of rheumatologic and autoimmune diseases. In
      addition, there have been developments in related medical disciplines that are
      relevant to the care of patients with rheumatic diseases. Keeping pace with these
      many developments is a challenge, and clinical rheumatologists have used various
      methods to educate themselves about these advances. In January 2012, the 5th
      annual Rheumatology Winter Clinical Symposium was held. At this meeting, faculty
      and participants held discussions and exchanged knowledge about new scientific
      data and how it may impact the care of rheumatology patients. Excerpts from some
      of the lectures from the Rheumatology Winter Clinical Symposium 2012 are included
      in this review. These and other presentations can be viewed in their entirety at
      http://www.r-w-c-s.com.

PMID- 22617483
TI  - Sedimentation equilibria of ferrofluids: I. Analytical centrifugation in
      ultrathin glass capillaries.
AB  - Analytical centrifugation is used for the first time to measure sedimentation
      equilibrium concentration profiles of a ferrofluid, a concentrated colloidal
      dispersion of strongly absorbing magnetic nanoparticles. To keep the optical
      absorbance from becoming too strong, the optical path length is restricted to 50
      MUm by placing the dispersion in a flat glass capillary. The concentration
      profile is kept from becoming too steep, despite the relatively high buoyant mass
      of the nanoparticles, by making novel use of a low-velocity analytical centrifuge
      that was not designed to measure equilibrium profiles. The experimental approach
      is validated by comparison with profiles obtained using an analytical
      ultracentrifuge. At concentrations of a few hundred grams per liter, the osmotic
      pressures calculated from the equilibrium profiles are lower than expected for
      hard spheres or non-interacting particles, due to magnetic dipolar interactions.
      By following the presented experimental approach, it will now also be possible to
      characterize the interparticle interactions of other strongly absorbing colloidal
      particles not studied before by analytical centrifugation.

PMID- 22617485
TI  - Some remarks on the compatibility between determinism and unpredictability.
AB  - Determinism and unpredictability are compatible since deterministic flows can
      produce, if sensitive to initial conditions, unpredictable behaviors. Within this
      perspective, the notion of scenario to chaos transition offers a new form of
      predictability for the behavior of sensitive to initial condition systems under
      the variation of a control parameter. In this paper I first shed light on the
      genesis of this notion, based on a dynamical systems approach and on
      considerations of structural stability. I then suggest a link to the figure of
      epigenetic landscape, partially inspired by a dynamical systems perspective, and
      offering a theoretical framework to apprehend developmental noise.

PMID- 22617484
TI  - The hybrid recombinational repair pathway operates in a chi activity deficient
      recC1004 mutant of Escherichia coli.
AB  - Homologous recombination is a crucial process for the maintenance of genome
      integrity. The two main recombination pathways in Escherichia coli (RecBCD and
      RecF) differ in the initiation of recombination. The RecBCD enzyme is the only
      component of the RecBCD pathway which acts in the initiation of recombination,
      and possesses all biochemical activities (helicase, 5'-3' exonuclease, chi
      cutting and loading of the RecA protein onto single-stranded (ss) DNA) needed for
      the processing of double stranded (ds) DNA breaks (DSB). When the nuclease and
      RecA loading activities of the RecBCD enzyme are inactivated, the proteins of the
      RecF recombination machinery, i.e., RecJ and RecFOR substitute for the missing 5'
      3' exonuclease and RecA loading activity respectively. The above mentioned
      activities of the RecBCD enzyme are regulated by an octameric sequence known as
      the chi site (5'-GCTGGTGG-3'). One class of recC mutations, designated recC*,
      leads to reduced chi cutting in vitro. The recC1004 strain (a member of the recC*
      mutant class) is recombination proficient and resistant to UV radiation. In this
      paper, we studied the effects of mutations in RecF pathway genes on DNA repair
      (after UV and gamma radiation) and on conjugational recombination in recC1004 and
      recC1004 recD backgrounds. We found that DNA repair after UV and gamma radiation
      in the recC1004 and recC1004 recD backgrounds depends on recFOR and recJ gene
      products. We also showed that the recC1004 mutant has reduced survival after
      gamma radiation. This phenotype is suppressed by the recD mutation which
      abolishes the RecBCD dependent nuclease activity. Finally, the genetic
      requirements for conjugational recombination differ from those for DNA repair.
      Conjugational recombination in recC1004 recD mutants is dependent on the recJ
      gene product. Our results emphasize the importance of the canonical chi
      recognition activity in DSB repair and the significance of interchange between
      the components of two recombination machineries in achieving efficient DNA
      repair.

PMID- 22617486
TI  - A semipopulation input function for quantifying static and dynamic 18F-fluoride
      PET scans.
AB  - PURPOSE: We describe a semipopulation input function for evaluating bone plasma
      clearance from static and dynamic (18)F-fluoride PET scans. METHODS: The
      semipopulation input function was derived by fitting an exponential curve to
      venous plasma measurements obtained 30-60 min after injection and adding a
      population residual curve representing the bolus peak scaled for injected
      activity and adjusted for time of peak counts. The residual curve was found from
      nine postmenopausal women who had continuous arterial blood samples and venous
      samples taken every 10 min. The precision errors of plasma clearance measurements
      derived from the semipopulation input function using Patlak analysis and the
      Hawkins compartmental model were compared with the precision errors for four
      image-derived input functions using data from 20 women who had undergone repeated
      dynamic PET scans. RESULTS: Venous and arterial concentrations were equal by 30
      min after injection. The exponential fitted to the 30-60-min venous data
      accounted for 76% of the total 0-60 min area under the curve, and the SD of the
      area under the residual curve was 2.6% of the total 0-60 min area under the
      curve. For Patlak analysis, the precision error (% coefficient of variation) was
      13.0% using the semipopulation input function compared with 14.9-21.7% using the
      four image-derived input functions. For the Hawkins model the equivalent figures
      were 14.5 and 20.1-30.9%, respectively. CONCLUSION: Accurate and precise
      measurements of bone plasma clearance were obtained when (18)F-fluoride PET scans
      were analysed using an input function obtained by adding a population residual
      curve to the exponential obtained from venous blood samples taken 30-60 min after
      injection.

PMID- 22617487
TI  - Response to "Tricyclic antidepressants intoxication in Tehran, Iran: epidemiology
      and associated factors".

PMID- 22617488
TI  - Oligomers of beta-amyloid protein (Abeta1-42) induce the activation of
      cyclooxygenase-2 in astrocytes via an interaction with interleukin-1beta, tumour
      necrosis factor-alpha, and a nuclear factor kappa-B mechanism in the rat brain.
AB  - Despite growing evidence indicating the effects of cytokines, including
      interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNFalpha), and the
      enzyme cyclooxygenase-2 (COX-2) in Alzheimer's diseases, little is known about
      the signalling mechanisms that mediate its activation in response to beta-amyloid
      protein (Abeta). The aim of this study was first to investigate whether Abeta1-42
      peptide induced the up-regulation of COX-2. We then examined the expression of
      COX-2 and cytokines, such as IL-1beta and TNFalpha, in reactive astrocytes.
      Finally, we analyzed the role of nuclear factor kappa-B (NF-kappaB) as a
      signalling pathway in early stages of Abeta-toxicity. In Wistar rats
      anaesthetised with equitesine, a single microinjection of Abeta1-42 oligomers was
      made in the left retrosplenial cortex. Control animals were injected with Abeta42
      1 peptide into the corresponding region of the cerebral cortex. By COX-2
      immunoblotting, we detected two immunopositive protein bands, at 70 and 50 kDa
      molecular mass. In the Abeta1-42-injected animals the 50 kDa fragment showed a
      significant increase at 3 and 14 days, as compared with that seen in control
      animals. The 70 kDa fragment showed a maximal increase at 14 days. In the Abeta1
      42-injected animals immunoblot staining of NF-kappaB detected an active protein
      band at 50 kDa molecular mass, showing a maximal increase at the 72 h time point.
      Confocal analysis revealed that COX-2 protein co-localized with Abeta-IR material
      at the injection site and in endothelial blood vessels, increasing at 72 h. In
      the Abeta oligomer-treated animals, COX-2, IL-1beta, and TNFalpha proteins were
      expressed in reactive astrocytes surrounding the injection site and blood vessels
      at early stages of Abeta toxicity. Double-labelling immunofluorescence studies
      also revealed that GFAP and COX-2 proteins co-localized with NF-kappaB-positive
      material at early time-points. In conclusion, our results suggest that in
      reactive astrocytes and in COX-2 positive cells NF-kappaB may mediate pro-,
      and/or inflammatory gene expression and that, develop strategies that target the
      GFAP/NF-kappaB and COX-2/NF-kappaB pathways might contribute to reducing Abeta
      induced toxicity.

PMID- 22617490
TI  - Synthesis of constrained benzocinnolinone analogues of CEP-26401 (irdabisant) as
      potent, selective histamine H3 receptor inverse agonists.
AB  - A novel class of benzocinnolinones analogs of irdabisant were designed and
      synthesized as histamine H3R antagonists/inverse agonists. Modifications to the
      pyridazinone portion of the core and linker led to the identification of
      molecules with excellent target potency and selectivity with improved rat
      pharmacokinetic properties and reduced potential hERG liabilities.

PMID- 22617489
TI  - Computational modeling of epilepsy for an experimental neurologist.
AB  - Computational modeling can be a powerful tool for an experimentalist, providing a
      rigorous mathematical model of the system you are studying. This can be valuable
      in testing your hypotheses and developing experimental protocols prior to
      experimenting. This paper reviews models of seizures and epilepsy at different
      scales, including cellular, network, cortical region, and brain scales by looking
      at how they have been used in conjunction with experimental data. At each scale,
      models with different levels of abstraction, the extraction of physiological
      detail, are presented. Varying levels of detail are necessary in different
      situations. Physiologically realistic models are valuable surrogates for
      experimental systems because, unlike in an experiment, every parameter can be
      changed and every variable can be observed. Abstract models are useful in
      determining essential parameters of a system, allowing the experimentalist to
      extract principles that explain the relationship between mechanisms and the
      behavior of the system. Modeling is becoming easier with the emergence of
      platforms dedicated to neuronal modeling and databases of models that can be
      downloaded. Modeling will never be a replacement for animal and clinical
      experiments, but it should be a starting point in designing experiments and
      understanding their results.

PMID- 22617491
TI  - The co-crystal structure of ubiquitin carboxy-terminal hydrolase L1 (UCHL1) with
      a tripeptide fluoromethyl ketone (Z-VAE(OMe)-FMK).
AB  - UCHL1 is a 223 amino acid member of the UCH family of deubiquitinating enzymes
      (DUBs), found abundantly and exclusively expressed in neurons and the testis in
      normal tissues. Two naturally occurring variants of UCHL1 are directly involved
      in Parkinson's disease (PD). Not only has UCHL1 been linked to PD, but it has
      oncogenic properties, having been found abnormally expressed in lung, pancreatic,
      and colorectal cancers. Although inhibitors of UCHL1 have been described
      previously the co-crystal structure of the enzyme bound to any inhibitor has not
      been reported. Herein, we report the X-ray structure of UCHL1 co-crystallized
      with a peptide-based fluoromethylketone inhibitor, Z-VAE(OMe)-FMK (VAEFMK) at
      2.35 A resolution. The co-crystal structure reveals that the inhibitor binds in
      the active-site cleft, irreversibly modifying the active-site cysteine; however,
      the catalytic histidine is still misaligned as seen in the native structure,
      suggesting that the inhibitor binds to an inactive form of the enzyme. Our
      structure also reveals that the inhibitor approaches the active-site cleft from
      the opposite side of the crossover loop as compared to the direction of approach
      of ubiquitin's C-terminal tail, thereby occupying the P1' (leaving group) site, a
      binding site perhaps used by the unknown C-terminal extension of ubiquitin in the
      actual in vivo substrate(s) of UCHL1. This structure provides a view of molecular
      contacts at the active-site cleft between the inhibitor and the enzyme as well as
      furnishing structural information needed to facilitate further design of
      inhibitors targeted to UCHL1 with high selectivity and potency.

PMID- 22617492
TI  - Disubstituted piperidines as potent orexin (hypocretin) receptor antagonists.
AB  - A series of orexin receptor antagonists was synthesized based on a substituted
      piperidine scaffold. Through traditional medicinal chemistry structure-activity
      relationships (SAR), installation of various groups at the 3-6-positions of the
      piperidine led to modest enhancement in receptor selectivity. Compounds were
      profiled in vivo for plasma and brain levels in order to identify candidates
      suitable for efficacy in a model of drug addiction.

PMID- 22617493
TI  - Prenylation at the indole ring leads to a significant increase of cytotoxicity of
      tryptophan-containing cyclic dipeptides.
AB  - Fourteen tryptophan-containing cyclic dipeptides 1a-14a, including all four
      stereoisomers of cyclo-Trp-Pro and cyclo-Trp-Ala, were converted to their C2
      regularly prenylated derivatives 1b-14b in the presence of dimethylallyl
      diphosphate by using the purified recombinant FtmPT1 as catalyst. The enzyme
      products were isolated on HPLC in preparative scales and their structures were
      elucidated by NMR and MS analyses. The cytotoxic effects of the prenylated
      products and their substrates were tested with human leukemia K562 and ovarian
      cancer A2780 sens and A2780 CisR cell lines. Preliminary results have been
      clearly shown that prenylation at C2 led to a significant increase of the
      cytotoxicity of the tested cyclic dipeptides in all the 14 cases. The second
      amino acid and the stereochemistry of tryptophan moiety of the cyclic dipeptides
      showed less influence on the cytotoxicity of the tested compounds.

PMID- 22617494
TI  - Prevalence of obesity in the United States, 2009-2010.
AB  - The most recent national data on obesity prevalence among U.S. adults,
      adolescents, and children show that more than one-third of adults and almost 17%
      of children and adolescents were obese in 2009-2010. Differences in prevalence
      between men and women diminished between 1999-2000 and 2009-2010, with the
      prevalence of obesity among men reaching the same level as that among women. Age
      differences in obesity prevalence varied between men and women. The prevalence of
      obesity was higher among older women compared with younger women, but there was
      no difference by age in obesity prevalence among men. Among children and
      adolescents, the prevalence of obesity was higher among adolescents than among
      preschool-aged children. There has been no change in obesity prevalence in recent
      years; however, over the last decade there has been a significant increase in
      obesity prevalence among men and boys but not among women and girls overall. The
      Healthy People 2010 goals of 15% obesity among adults and 5% obesity among
      children were not met (6).

PMID- 22617495
TI  - Frontotemporal white-matter microstructural abnormalities in adolescents with
      conduct disorder: a diffusion tensor imaging study.
AB  - BACKGROUND: Children with conduct disorder (CD) are at increased risk of
      developing antisocial personality disorder (ASPD) and psychopathy in adulthood.
      The biological basis for this is poorly understood. A preliminary diffusion
      tensor magnetic resonance imaging (DT-MRI) study of psychopathic antisocial
      adults reported significant differences from controls in the fractional
      anisotropy (FA) of the uncinate fasciculus (UF), a white-matter tract that
      connects the amygdala to the frontal lobe. However, it is unknown whether
      developmental abnormalities are present in the UF of younger individuals with CD.
      METHOD: We used DT-MRI tractography to investigate, for the first time, the
      microstructural integrity of the UF in adolescents with CD, and age-related
      differences in this tract. We compared FA and perpendicular diffusivity of the UF
      in 27 adolescents with CD and 16 healthy controls (12 to 19 years old) who did
      not differ significantly in age, IQ or substance use history. To confirm that
      these findings were specific to the UF, the same measurements were extracted from
      two non-limbic control tracts. Participants in the CD group had a history of
      serious aggressive and violent behaviour, including robbery, burglary, grievous
      bodily harm and sexual assault. RESULTS: Individuals with CD had a significantly
      increased FA (p = 0.006), and reduced perpendicular diffusivity (p = 0.002), in
      the left UF. Furthermore, there were significant age-related between-group
      differences in perpendicular diffusivity of the same tract (Z obs = 2.40, p =
      0.01). Controls, but not those with CD, showed significant age-related
      maturation. There were no significant between-group differences in any measure
      within the control tracts. CONCLUSIONS: Adolescents with CD have significant
      differences in the 'connectivity' and maturation of UF.

PMID- 22617496
TI  - Identification of Th1 epitopes within molecules from the lung-stage
      schistosomulum of Schistosoma japonicum by combining prediction analysis of the
      transcriptome with experimental validation.
AB  - The lung-stage schistosomulum has been regarded as the main target of protective
      immunity induced by radiation-attenuated vaccines (RAV) in the mouse model of
      schistosomiasis, and immune mechanisms mediated by the CD4+ Th1 response play a
      major role in the RAV model. To identify Th1 epitopes rapidly within molecules
      from the lung schistosomulum of Schistosoma japonicum, in the present study we
      analyzed transcriptome data from normal and radiation-attenuated lung
      schistosomula of S. japonicum and Schistosoma mansoni. We selected six genes with
      high levels of expression of their transcripts as sample sequences from the lung
      schistosomula. From these six sequences, by using different algorithms, we
      predicted six promiscuous Th cell epitopes that are capable of binding to both
      murine and human MHC class II molecules. To validate our in silico prediction
      experimentally, first, the gene expressions of the six sequences in day 3 lung
      stage schistosomula were assessed using reverse-transcription PCR (polymerase
      chain reaction) analysis. The result showed that all six sequences predicted can
      be expressed in normal day 3 schistosomula. Second, we measured the direct
      binding of the four peptides predicted above to APCs (Antigen Presenting Cells)
      from the BALB/c mouse strain using a fluorometric method, and found that the four
      peptides could bind to both I-Ad and I-Ed molecules of the mice. Finally, the
      proliferation and profiles of cytokine production by spleen lymphocytes from the
      BALB/c mice immunized with the six predicted peptides were detected in vitro
      using modified MTT (Methyl Thiazolyl Tetrazolium), and flow cytometry methods,
      respectively. The results showed that three of the six predicted peptides could
      induce a recall CD4+ Th1 response in vitro. These results demonstrate that
      potential Th1-type epitopes can be identified rapidly by a combination of in
      silico analysis of transcriptomes of lung-stage schistosomula with experimental
      validation.

PMID- 22617497
TI  - MPI CyberMotion Simulator: implementation of a novel motion simulator to
      investigate multisensory path integration in three dimensions.
AB  - Path integration is a process in which self-motion is integrated over time to
      obtain an estimate of one's current position relative to a starting point (1).
      Humans can do path integration based exclusively on visual (2-3), auditory (4),
      or inertial cues (5). However, with multiple cues present, inertial cues -
      particularly kinaesthetic - seem to dominate (6-7). In the absence of vision,
      humans tend to overestimate short distances (<5 m) and turning angles (<30
      degrees ), but underestimate longer ones (5). Movement through physical space
      therefore does not seem to be accurately represented by the brain.    Extensive
      work has been done on evaluating path integration in the horizontal plane, but
      little is known about vertical movement (see (3) for virtual movement from vision
      alone). One reason for this is that traditional motion simulators have a small
      range of motion restricted mainly to the horizontal plane. Here we take advantage
      of a motion simulator (8-9) with a large range of motion to assess whether path
      integration is similar between horizontal and vertical planes. The relative
      contributions of inertial and visual cues for path navigation were also assessed.
      16 observers sat upright in a seat mounted to the flange of a modified KUKA
      anthropomorphic robot arm. Sensory information was manipulated by providing
      visual (optic flow, limited lifetime star field), vestibular-kinaesthetic
      (passive self motion with eyes closed), or visual and vestibular-kinaesthetic
      motion cues. Movement trajectories in the horizontal, sagittal and frontal planes
      consisted of two segment lengths (1st: 0.4 m, 2nd: 1 m; +/-0.24 m/s(2) peak
      acceleration). The angle of the two segments was either 45 degrees  or 90 degrees
      . Observers pointed back to their origin by moving an arrow that was superimposed
      on an avatar presented on the screen.    Observers were more likely to
      underestimate angle size for movement in the horizontal plane compared to the
      vertical planes. In the frontal plane observers were more likely to overestimate
      angle size while there was no such bias in the sagittal plane. Finally, observers
      responded slower when answering based on vestibular-kinaesthetic information
      alone. Human path integration based on vestibular-kinaesthetic information alone
      thus takes longer than when visual information is present. That pointing is
      consistent with underestimating and overestimating the angle one has moved
      through in the horizontal and vertical planes respectively, suggests that the
      neural representation of self-motion through space is non-symmetrical which may
      relate to the fact that humans experience movement mostly within the horizontal
      plane.

PMID- 22617498
TI  - Children's speech recognition and loudness perception with the Desired Sensation
      Level v5 Quiet and Noise prescriptions.
AB  - PURPOSE: To determine whether Desired Sensation Level (DSL) v5 Noise is a viable
      hearing instrument prescriptive algorithm for children, in comparison with DSL v5
      Quiet. In particular, the authors compared children's performance on measures of
      consonant recognition in quiet, sentence recognition in noise, and loudness
      perception when fitted with DSL v5 Quiet and Noise. METHOD: Eleven children (ages
      8 to 17 years) with stable, congenital sensorineural hearing losses participated
      in the study. Participants were fitted bilaterally to DSL v5 prescriptions with
      behind-the-ear hearing instruments. The order of prescription was counterbalanced
      across participants. Repeated measures analysis of variance was used to compare
      performance between prescriptions. RESULTS: Use of the Noise prescription
      resulted in a significant decrease in consonant perception in Quiet with low
      level input, but no difference with average-level input. There was no significant
      difference in sentence-in-noise recognition between the two prescriptions.
      Loudness ratings for input levels above 72 dB SPL were significantly lower with
      the noise prescription. CONCLUSIONS: Average-level consonant recognition in quiet
      was preserved and aversive loudness was alleviated by the Noise prescription
      relative to the quiet prescription, which suggests that the DSL v5 Noise
      prescription may be an effective approach to managing the nonquiet listening
      needs of children with hearing loss.

PMID- 22617499
TI  - Adiposity and physical activity are not related to academic achievement in school
      aged children.
AB  - OBJECTIVE: To investigate the hypotheses that in elementary school students: (1)
      adiposity and academic achievement are negatively correlated and (2) physical
      activity and academic achievement are positively correlated. METHODS:
      Participants were 1963 children in fourth to sixth grades. Adiposity was assessed
      by calculating body mass index (BMI) percentile and percent body fat and academic
      achievement with statewide standardized tests in 4 content areas. Socioeconomic
      status and age were control variables. A subset of participants (n = 261) wore an
      accelerometer for 3 days to provide objective measurement of physical activity.
      In addition, the association between weight status and academic achievement was
      examined by comparing children who could be classified as "extremely obese" and
      the rest of the sample, as well as comparing children who could be classified as
      normal weight, overweight, or obese. Extreme obesity was defined as >=1.2 times
      the 95th percentile. RESULTS: The results indicated that there were no
      significant associations between adiposity or physical activity and achievement
      in students. No academic achievement differences were found between children with
      BMI percentiles within the extreme obesity range and those who did not fall
      within the extreme obesity classification. In addition, no academic achievement
      differences were found for children with BMI percentiles within the normal
      weight, overweight, or obese ranges. CONCLUSIONS: These results do not support
      the hypotheses that increased adiposity is associated with decreased academic
      achievement or that greater physical activity is related to improved achievement.
      However, these results are limited by methodological weaknesses, especially the
      use of cross-sectional data.

PMID- 22617500
TI  - Static sac size with a type II endoleak post-endovascular abdominal aortic
      aneurysm repair: surveillance or embolization?
AB  - A best evidence topic was written according to a structured protocol. The
      question addressed was whether embolization is superior to surveillance for a
      type II endoleak associated with a static sac size post-endovascular abdominal
      aortic aneurysm repair (EVAR). Four hundred and sixty-one papers were identified,
      of which 10 papers presented the best evidence to answer the clinical question.
      The author, journal, date and country of publication, patient group studied,
      study type, and relevant outcomes and results are tabulated. A review of the
      available literature suggests that most type II endoleaks are innocuous and will
      seal spontaneously during the long-term follow-up, even when they persist for
      more than 6 months. An analysis of the large European Collaborators on Stent
      Graft Techniques for Aortic Aneurysm Repair (EUROSTAR) registry that includes
      prospective data on 2463 patients from 87 European hospitals showed that type II
      endoleaks were not associated with an increased risk of rupture; this correlates
      well with the large single-centre studies included in this review. Based on the
      available evidence, we conclude that the management of most isolated type II
      endoleaks should be conservative-with close radiological follow-up--even when
      persistent, with intervention restricted to theoese associated with sac
      enlargement >5 mm over a 6-month period or >10 mm when compared with pre-EVAR
      diameter.

PMID- 22617501
TI  - Non-Fas(CD95/APO1)-mediated apoptosis of activated T cells inhibits the
      development of atherosclerosis.
AB  - Atherosclerosis is a chronic systemic inflammatory disease. The innate and
      adaptive immune response might be involved in atherogenesis. Methotrexate (MTX)
      induces apoptosis of activated T cells by a CD95-independent pathway. The aim of
      this study was to analyse the effect of immunomodulation by MTX in the
      development of early atherosclerotic vascular lesions in an animal model. Four
      week old male C57BL6 LDL-receptor-deficient mice were fed a diet rich in
      saturated fat (82%) and cholesterol (2.8%). Thirty animals were given a weekly
      intramuscular injection of MTX, establishing three subgroups: 10, 30 and 50
      mg/kg. Ten further mice were used as an immunocompetent control group. Aortic
      thickening was significantly inhibited in all MTX-treated groups compared with
      the control group at 30 days (0.46 +/- 0.003 mm(2) in the control group vs 0.31
      +/- 0.002, 0.14 +/- 0.009 and 0.16 +/- 0.006 mm(2) in the low-, intermediate- and
      high-dose group, respectively; P = 0.01) and at 60 days. The aortic lumen/total
      area ratio was also increased in the MTX-treated groups (0.82 +/- 0.06 in the
      control group vs 0.88 +/- 0.07, 0.86 +/- 0.05 and 0.88 +/- 0.04, respectively; P
      = 0.02). Immunosuppression by MTX inhibits the development of atherosclerotic
      lesions in arterial vessels in mice, which highlights the crucial role of the
      immune system in atherogenesis.

PMID- 22617502
TI  - An anomalous segmental vein of the left upper lobe of the lung: preoperative
      identification by three-dimensional computed tomography pulmonary angiography.
AB  - A number of variations in the pulmonary arteries and veins have been documented,
      and the information is very important for performing a safe lung resection. This
      report describes a case of an anomalous segmental vein of the left upper lobe of
      the lung. The patient was a 75-year old male who was suspected to have lung
      cancer in the left upper lobe. A contrast-enhanced computed tomography showed a
      vessel behind the left lower bronchus. A three-dimensional computed tomography
      angiography demonstrated that it was an anomalous vein for the apicoposterior
      segment of the left upper lobe of the lung, draining into the left inferior
      pulmonary vein. The aberrant vein was readily identified during surgery and was
      divided without injury, and a left upper lobectomy was successfully performed.
      Aberrant pulmonary veins for the superior segment of the right upper lobe of the
      lung are rarely observed, and the same kind of anomaly on the left side has not
      been reported.

PMID- 22617503
TI  - Re-sternotomy as an unwelcome side-effect of unknown effervescent tablet intake?
AB  - Four hours after surgery for aortic valve stenosis and tricuspid valve
      regurgitation, an unknown foreign body was present on the routine chest X-ray. We
      performed re-sternotomy in order to retrieve this foreign body. The foreign body
      was easy to move on fluoroscopy but we could not extract it. We concluded that
      the foreign body was in a subdiaphragmatic location. As a consequence, we
      performed gastroscopy. A white, frothy mass (similar to an undissolved
      effervescent tablet) within an ulcerated lesion was seen and partially extracted.

PMID- 22617504
TI  - Is it worth placing ventricular pacing wires in all patients post-coronary artery
      bypass grafting?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was whether ventricular pacing wires should be
      placed routinely in all patients undergoing coronary artery bypass grafting
      (CABG) regardless of immediate post-cardiopulmonary bypass (CPB) rhythm status.
      Using the reported search, 142 papers were found, from which 10 papers
      represented the best evidence on the subject. The author, date and country of 10
      publications, study type, patient group studied, relevant outcomes and results
      are tabulated. Complete atrio-ventricular (AV) block is the main reason for
      inserting ventricular pacing wires upon conclusion of CABG. Eight studies found
      complete AV block to be a rare entity post-CABG. The rate of complete AV block in
      CABG in our review ranged from 0.3 to 24%. The calculated average rate of AV
      block in all studies was 2.4%. The number needed to treat with ventricular wires
      to support a patient who develops AV block is 42. One randomized controlled trial
      found 3% risk of complete AV block post-CABG. Another cohort of 222 patients
      revealed a rate of 1.8% for complete AV block. For one cohort of 770 patients,
      post-CABG the rate of complete AV block was found to be 0.3%. In one cohort of 25
      patients, there was a rate of 4% for complete AV block post-CABG. Another study
      of 564 patients revealed a rate of 0.7% for complete AV block. A study of 4999
      patients post-CABG reported a rate of 1.2% for complete AV block. In one cohort
      of 93 patients, there was a 4% risk of complete AV block. Another cohort of 62
      patients showed a rate of 1.6% for complete AV block. Only two papers found the
      rate of complete AV block post-CABG to be as high as 24 and 16%. Both studies
      were limited by sample size. In conclusion, routine ventricular pacing wire
      insertion post-CABG is unnecessary given that routine use of ventricular wires
      can occasionally cause complications such as bleeding and cardiac tamponade and
      thus is not risk free. We also found that the incidence of complete AV block is
      probably higher in on-CPB CABG than off-CPB CABG and that AV pacing may be
      haemodynamically beneficial for some patients postoperatively.

PMID- 22617505
TI  - The profile of the systemic inflammatory response in children undergoing
      ventricular assist device support.
AB  - OBJECTIVES: Serum C-reactive protein (CRP) has been used as a systemic
      inflammatory response (SIR) marker in the critical ill, including children after
      cardiopulmonary bypass surgery. Ventricular assist devices (VAD) have been
      increasingly used as a bridge support to heart transplantation in children. We
      aimed to examine the profiles of CRP in children receiving VAD support. METHODS:
      Charts of 13 children receiving Berlin Heart EXCOR((r)) from 2005 to 2009 were
      reviewed. The data obtained prior to and during VAD support included: CRP, white
      blood cells, inotropes and steroid use, VAD mode and duration of VAD support. Ten
      patients received left VAD (LVAD) and 3 biventricular VAD (BiVAD). RESULTS: The
      median duration of VAD support was 59 days (ranged 3-678 days). Pre-VAD CRP was
      35 +/- 51 mg/l and increased to 109 +/- 59 mg/l on days 1-3 after the VAD
      implantation (P = 0.01), then gradually decreased to 28 +/- 28 mg/l by 4 months
      and normalized by 5 months (P < 0.0001). CRP was higher in BiVAD than in LVAD
      patients throughout the study period (P = 0.003). CRP positively correlated with
      the doses of the epinephrine and norepinephrine and the monocyte counts, and
      negatively correlated with the lymphocyte count. The lymphocyte count was 2.5 +/-
      0.4 x 10(9)/l prior to implantation, and decreased to 2.1 +/- 1.3 x 10(9)/l on
      days 1-3 (P = 0.5) and then to 0.6 +/- 0.1 x 10(9)/l by 6 months (P = 0.08). It
      tended to be lower in BiVAD patients (P = 0.06). CONCLUSIONS: SIR exists in
      children prior to VAD support. VAD implantation is associated with a significant
      and prolonged increase in CRP and a decrease in lymphocyte count, indicating a
      suppressed immune function, being more pronounced in BiVAD patients.

PMID- 22617506
TI  - Perceval S aortic valve implantation in mini-invasive surgery: the simple
      sutureless solution.
AB  - The Perceval S bioprosthesis (21 and 23 mm) was approved for clinical use in
      December 2010 and it is now routinely used. This bioprosthesis is suggested for
      the treatment of patients undergoing minimally-invasive surgery for reasons of
      safety and reduction in implantation time. Here we describe the use of the
      Perceval bioprosthesis in patients undergoing minimally invasive cardiac surgery.

PMID- 22617507
TI  - Salvage therapy with topical antifungal for Aspergillus fumigatus empyema
      complicating extrapleural pneumonectomy.
AB  - We describe an unusual case of Aspergillus fumigatus empyema and bronchopleural
      fistulae after extrapleural pneumonectomy (EPP) and chemoradiotherapy (CRT),
      which was treated successfully under salvage conditions with debridement, an
      innovative topical antifungal application and supplemented systemic antifungal
      therapy and which went on for a definitive surgical procedure. Combinations of
      CRT and EPP have been recommended in a select group of patients with malignant
      mesothelioma. Irrespective of the combination, EPP is associated with mortality
      in the range of 4-15% and a complication rate as high as 62%.

PMID- 22617508
TI  - Neuronal antibodies and paraneoplastic sensory neuropathy in thymoma.
AB  - Thymoma, a common anterior mediastinal tumour, may present with paraneoplastic
      neurological symptoms. The presence of neuronal anti-Hu paraneoplastic antibodies
      in thymoma patients is very rare. Here, we describe a patient who presented with
      symptoms of a sensory peripheral neuropathy in the presence of onconeural
      antibodies cross-reactive with Hu antigen, in whom an underlying thymoma was
      diagnosed. Subsequent minimally invasive thymomectomy improved her neurological
      symptoms significantly.

PMID- 22617509
TI  - Myxoma of the aortic valve.
AB  - Myxomatous tumours can arise from different cardiac structures. They have a
      special predilection for the left atrium and are an exceedingly uncommon finding
      in cardiac valves. We report the case of a 28-year old man who presented with a
      stroke and was found to have a mass arising from his aortic valve. The patient
      underwent a successful surgical excision of the aortic valve with the
      implantation of a mechanical prosthesis. The histopathological examination of the
      aortic valve confirmed the diagnosis of myxoma. Some aspects related to the
      diagnosis and management of this entity are discussed in this article.

PMID- 22617510
TI  - Does a conservative fluid management strategy in the perioperative management of
      lung resection patients reduce the risk of acute lung injury?
AB  - A best evidence topic in thoracic surgery was written according to a structured
      protocol. The question addressed was whether a conservative fluid management
      strategy in the perioperative management of lung resection patients is associated
      with a reduced incidence of postoperative acute lung injury (PALI) and/or acute
      respiratory distress syndrome (ARDS) in the recovery period. Sixty-seven papers
      were found using the reported search, of which 13 level III and 1 level IV
      evidence studies represented the best evidence to answer the question. Two
      retrospective case-control studies demonstrated a direct association between
      liberal fluid intake and the incidence of PALI/ARDS following lung resection on
      multivariate analysis (MVA) with odds ratios (ORs) of 1.42 (95% CI 1.09-4.32, P =
      0.011) and 2.91 (1.9-7.4, P = 0.001). In non-PALI/ARDS cases, the mean
      intraoperative fluid infusion volume was significantly less [1.22 l (1.17-1.26)
      vs 1.68 l (1.46-1.9) P = 0.005], the fluid balance over the first 24
      postoperative hours was significantly less [1.52 l positive (1.44-1.60) vs 2.0 l
      positive (1.6-2.4) P = 0.026] and cumulated intra- and postoperative fluid
      infusion was significantly less [2.0 ml/kg/h (1.7-2.3) vs 2.6 ml/kg/h (2.3-2.9) P
      = 0.003]. These data show that the difference between fluid regimes associated
      with an increased incidence of PALI/ARDS (i.e. 'liberal') and those which are not
      (i.e. 'conservative') is narrow but significant. However, this does not prove a
      causative role for liberal fluid in the multifactorial development of PALI/ARDS.
      On this best evidence, we recommend intra- and postoperative maintenance fluid to
      be administered at 1-2 ml/kg/h and that a positive fluid balance of 1.5 l should
      not be exceeded in the perioperative period with caution being exercised with
      regard to the adequacy of oxygen delivery. If the fluid balance exceeds this
      threshold, a high index of suspicion for PALI/ARDS should be adopted and
      escalation of the level of care should be considered. If a patient develops signs
      of hypoperfusion after these thresholds are exceeded, inotropic/vasopressor
      support should be considered.

PMID- 22617511
TI  - A tethering coherent protein in autophagosome maturation.
AB  - Autophagy is a cellular pathway that degrades damaged organelles, cytosol and
      microorganisms, thereby maintaining human health by preventing various diseases
      including cancers, neurodegenerative disorders and diabetes. In autophagy,
      autophagosomes carrying cellular cargoes fuse with lysosomes for degradation. The
      proper autophagosome-lysosome fusion is pivotal for efficient autophagy activity.
      However, the molecular mechanism that specifically directs the fusion process is
      not clear. Our study reported that lysosome-localized TECPR1 (TECtonin beta
      Propeller Repeat containing 1) binds the autophagosome-localized ATG12-ATG5
      conjugate and recruits it to autolysosomes. TECPR1 also binds PtdIns3P in an
      ATG12-ATG5-dependent manner. Consequently, depletion of TECPR1 leads to a severe
      defect in autophagosome maturation. We propose that the interaction between
      TECPR1 and ATG12-ATG5 initiates the fusion between the autophagosome and
      lysosome, and TECPR1 is a TEthering Coherent PRotein in autophagosome maturation.

PMID- 22617512
TI  - Crosstalk between the UPR and autophagy pathway contributes to handling cellular
      stress in neurodegenerative disease.
AB  - Huntington disease (HD) is caused by an extended polyglutamine [poly(Q)] stretch
      in the Huntingtin (HTT) protein, and is associated with the accumulation of
      intracellular protein aggregates, onset of progressive chorea, psychiatric
      symptoms and dementia. Although the mechanism underlying the pathological effects
      of mutant HTT (mHTT) remains highly controversial, accumulating evidence suggest
      that protein-folding stress at the endoplasmic reticulum (ER) may contribute to
      mHTT-mediated degeneration. ER stress is alleviated by the activation of an
      adaptive reaction known as the unfolded protein response (UPR), whereas chronic
      ER stress triggers apoptosis by the same pathway. However, most of the studies
      linking ER stress with HD in vivo are correlative. UPR signaling is initiated by
      the activation of at least three distinct stress sensors located at the ER
      membrane known as ERN1/IRE1alpha, EIF2AK3/PERK and ATF6. These stress sensors
      control the expression of specialized transcription factors that modulate the
      upregulation of a variety of target genes involved in folding, protein quality
      control, autophagy and protein synthesis.

PMID- 22617513
TI  - Neurodevelopmental disorders: unlocking the secrets of autism through whole-exome
      sequencing.

PMID- 22617522
TI  - Receptor-mediated transcytosis: a mechanism for active extravascular transport of
      nanoparticles in solid tumors.
AB  - Targeted nanoparticle-based delivery systems have been used extensively to
      develop effective cancer theranostics. However, how targeting ligands affect
      extravascular transport of nanoparticles in solid tumors remains unclear. Here,
      we show, using B16/F10 melanoma cells expressing melanocortin type-1 receptor
      (MC1R), that the nature of targeting ligands, i.e., whether they are agonists or
      antagonists, directs tumor uptake and intratumoral distribution after
      extravasation of nanoparticles from tumor vessels into the extravascular fluid
      space. Pegylated hollow gold nanospheres (HAuNS, diameter=40 nm) coated with MC1R
      agonist are internalized upon ligand-receptor binding, whereas MC1R antagonist
      conjugated HAuNS remain attached on the cell surface. Transcellular transport of
      agonist-conjugated HAuNS was confirmed by a multilayer tumor cell model and by
      transmission electron microscopy. MC1R agonist- but not MC1R antagonist
      conjugated nanoparticles exhibit significantly higher tumor uptake than
      nontargeted HAuNS and are quickly dispersed from tumor vessels via receptor
      mediated endocytosis and subsequent transcytosis. These results confirm an active
      transport mechanism that can be used to overcome one of the major biological
      barriers for efficient nanoparticle delivery to solid tumors.

PMID- 22617521
TI  - Enhanced skin permeation using polyarginine modified nanostructured lipid
      carriers.
AB  - The objective of the present study was to investigate the effect of polyarginine
      chain length on topical delivery of surface modified NLCs. Design of experiments
      (DOE) was used to optimize number of arginines required to deliver active drug
      into deeper skin layers. The NLCs were prepared by hot-melt technique and the
      surface of NLCs was modified with six-histidine tagged cell penetrating peptides
      (CPPs) or YKA. In vivo confocal microscopy and Raman confocal spectroscopy
      studies were performed using fluorescent dye encapsulated NLCs and NLC-CPPs.
      Spantide II (SP) and ketoprofen (KP) were used as model drugs for combined
      delivery. In vitro skin permeation and drug release studies were performed using
      Franz diffusion cells. Inflammatory response corresponding to higher skin
      permeation was investigated in allergic contact dermatitis (ACD) mouse model.
      NLCs had a particle size of 140+/-20nm with higher encapsulation efficiencies.
      The negative charge of NLC was reduced from -17.54 to -8.47 mV after surface
      modification with CPPs. In vivo confocal microscopy and Raman confocal
      spectroscopy studies suggested that a peptide containing 11 arginines (R11) had
      significant permeation enhancing ability than other polyarginines and TAT
      peptides. The amount of SP and KP retained in dermis after topical application of
      NLC-R11 was significantly higher than solution and NLC after 24 h of skin
      permeation. SP was not found in receiver compartment. However, KP was found in
      receiver compartment and the amount of KP present in receiver compartment was
      increased approximately 7.9 and 2.6 times compared to the control solution and
      NLCs, respectively. In an ACD mouse model, SP+KP-NLC-R11 showed significant
      reduction (p<0.05) in ear thickness compared to SP+KP solution and SP+KP-NLC. Our
      results strongly suggest that the surface modification of NLC with R11 improved
      transport of SP and KP across the deeper skin layers and thus results in
      reduction of inflammation associated with ACD.

PMID- 22617523
TI  - Utility of closed suction pelvic drains at time of large bowel resection for
      ovarian cancer.
AB  - OBJECTIVE: To test the hypothesis that the use of closed suction pelvic drains
      placed at time of large bowel resection (LBR) for ovarian cancer (OC) decreases
      morbidity following anastomotic leak (AL). METHODS: Consecutive cases of LBR for
      OC between 01/01/1994 and 06/20/2011 were retrospectively identified. Drains were
      routinely used until bowel movement. AL was defined as: 1) feculent fluid from
      drains/wound/vagina, 2) radiographic evidence of AL, or 3) AL found at
      reoperation. Descriptive statistics, Wilcoxon rank-sum, Pearson's chi-square and
      Fisher's exact test were used. RESULTS: 43 cases met inclusion criteria. AL was
      characterized by method of diagnosis as follows: change in drain output only (DO,
      n=8); change in drain output associated with ambiguous clinical signs/symptoms (D
      SSX, n=11); or clinical signs/symptoms only (SSX, n=24). The sensitivity of
      drains in diagnosing AL was 50%. Time to diagnosis was earlier in DO/D-SSX
      (median 7 vs. 11 days, P=0.003), however, no significant differences were
      observed in rates of reoperation, length of stay, time to chemotherapy (TTC), and
      30- and 90-day mortality between DO/D-SSX and SSX. Comparing cases where no
      drains were placed (n=5) vs. those with drain (n=38), we observed no differences
      in outcomes. TTC though statistically significant (47 vs. 59 days, P=0.023) was
      not clinically significant. CONCLUSIONS: Though a change in drain output
      correlated with earlier diagnosis, this did not appear to impact overall
      outcomes. We did not find strong evidence supporting routine prolonged drainage
      after LBR for OC. Additionally, absence of change in drain output does not rule
      out presence of AL.

PMID- 22617526
TI  - [Helicobacter pylori in human stomach: can it be called mutualism or a disease?].
AB  - Helicobacter pylori (H. pylori) has been a major concern as a gastric pathogen
      with unique features since discovered in the end of the 20th century. Recent data
      on comparative genome study have revealed that H. pylori has successfully
      survived with its host though over 58,000 years of evolution and migration from
      continent to continent. To maintain the symbiotic relationship with human, H.
      pylori has come up with ways to induce host tolerance as well as exert harmful
      injuries. Studies about H. pylori have accumulated the knowledge about how the
      cellular and molecular interactions are controlled and regulated to decide
      whether the symbiotic relationship is directed to diseases or peaceful mutualism.
      We reviewed recent literatures and research outcomes about the H. pylori and host
      interaction in molecular and cellular basis.

PMID- 22617524
TI  - Clinical and pathologic features of young endometrial cancer patients with loss
      of mismatch repair expression.
AB  - OBJECTIVE: This study examines premenopausal and early menopause patients in a
      unique population with endometrial cancer and loss of mismatch repair (MMR) gene
      expression. The purpose is to compare clinical and pathologic differences in
      patients with loss of expression (LOE) to those with normal expression (NE).
      METHODS: Endometrial cancer patients under age 60 in-between 1998 and 2008 were
      identified from a single tumor registry. Clinical and pathologic data were
      abstracted from records. Staining for expression of MSH6, MSH2, MLH1, and PMS2
      were performed on archived tissue blocks. Statistical analysis was performed.
      RESULTS: 158 patients were analyzed; 58% Asian, 34% Pacific Islander, and 8%
      Caucasian. 31 demonstrated LOE of at least one MMR gene; 127 retained NE. 50%
      Caucasian, 21.9% Asian, and 12.5% Pacific Island populations had LOE of one or
      more MMR genes. LOE was found to have a higher incidence of Grade III (p=0.0013)
      and stage 3-4 tumors (p=0.0079), mean depth of myometrial invasion (p=0.0019),
      lymphovascular space invasion (p=0.0020), nodal metastases (p=0.0157), and a
      lower incidence of Grade I (p=0.0020) and stage 1A tumors (p=0.0085). LOE had a
      significantly lower mean BMI (p=0.0001). 35% of patients in the NE vs zero in the
      LOE group had a BMI greater than 40. CONCLUSION: Younger patients with LOE
      endometrial cancer appear to represent a clinically significant subgroup of
      patients without features characteristically found in classic type 1 endometrial
      cancer generally demonstrating lower BMI and tumors associated with poor
      prognostic characteristics. It is unclear if the distinctive ethnicity found in
      Hawaii has a significant impact on outcome. Further investigation is necessary to
      identify appropriate treatment strategies.

PMID- 22617527
TI  - [Clinical characteristics of patients diagnosed as peptic ulcer disease in the
      third referral center in 2007].
AB  - BACKGROUND/AIMS: In spite of the improvement of medical treatment for the peptic
      ulcer disease (PUD), PUD is still one of the common upper gastrointestinal
      diseases. The purpose of this study was to evaluate the risk factors and general
      characteristics of Korean patients diagnosed as PUD at a single third referral
      center. METHODS: A total of 310 patients, diagnosed as PUD through endoscopy
      during one year of 2007 at Seoul National University Bundang Hospital were,
      retrospectively, evaluated regarding age, gender, Helicobacter pylori (H. pylori)
      positivity, clinical manifestations, comorbidities and medications. In addition,
      PUD was analyzed in the aspect of ulcer location, type of visit, gastrointestinal
      bleeding, and age. RESULTS: The mean age was 61.5 years old (48.1% over 65) and
      208 (66.7%) patients were men. The rate of H. pylori infection was 47.8%, and any
      ulcerogenic medication history such as antiplatelet agents and NSAIDs was found
      to be 21.0% (65 patients). The rate of idiopathic peptic ulcer without evidence
      of H. pylori and NSAIDs was found to be 40.6% (126 patients). Among 310 PUD
      patients, bleeding symptoms such as melena, hematemesis and hematochezia occurred
      in 110 patients (35.5%). CONCLUSIONS: PUD was more prevalent in the elderly
      patients and frequently associated with bleeding. Substantial proportion of PUD
      patients had neither H. pylori infection nor history of ulcerogenic medications,
      suggesting of increasing prevalence of idiopathic PUD.

PMID- 22617528
TI  - [Usefulness of 18F-fluoro-2-deoxyglucose positron emission tomography in
      evaluation of gastric cancer stage].
AB  - BACKGROUND/AIMS: The usefulness of 18F-fluoro-2-deoxyglucose (FDG)-PET in
      detecting primary cancer, lymph node metastasis, and distant metastasis were
      studied in the gastric cancer patients. METHODS: The subjects were 392 gastric
      cancer patients who received FDG-PET and an abdominal CT test prior to surgery.
      The results of FDG-PET and CT were compared with the surgical and pathologic
      results. RESULTS: The primary site detection rate of FDG-PET was 74.4%, 50.3% in
      early gastric cancer and 92.0% in advanced gastric cancer. Detection rate was
      higher when tumors were larger than 3.5 cm, had deeper depth of invasion, and at
      a later stage (p<0.05, respectively). In multivariate analysis, tumor size,
      spread of tumor cells beyond the muscle layer (>=T2), and lymph node metastasis
      were statistically significant factors in primary site detection rate. The
      sensitivity, specificity, and positive predictive value of FDG-PET to lymph node
      metastasis were 59.6%, 88.8%, and 81.1% respectively, sensitivity being lower
      compared to CT while specificity and positive predictive value were higher.
      Sensitivity, specificity, and positive predictive value to distant metastasis
      were, respectively, 66.7%, 99.2%, and 88.0%, similar to CT. In 21 of the 392
      patients (5.4%), synchronous double primary cancers were detected. CONCLUSIONS:
      In gastric cancer, usefullness of FDG-PET is limited to the advanced stage.
      Diagnostic value of this test was not superior to CT. However, FDG-PET may be
      useful in detecting synchronous double primary cancers.

PMID- 22617529
TI  - Predictable factors of histologic discrepancy of gastric cancer between the
      endoscopic forceps biopsy and endoscopic treatment specimen.
AB  - BACKGROUND/AIMS: Recently, variable gastrointestinal track tumors including early
      stage malignancies are treated by endoscopic procedure. However, the discrepancy
      of histologic diagnosis may sometimes exist between the pretreatment forceps
      biopsy results and those of post treatment specimen. So the prediction of
      malignant lesion is important in the aspect of treatment selection. In this
      study, we investigated the predictable factors of the histologic discrepancy
      through the clinical, endoscopic features of the lesion diagnosed as
      adenocarcinoma in the post-endoscopic treatment specimen after the adenoma was
      diagnosed by the endoscopic forceps biopsy. METHODS: From March 2005 to April
      2009, 129 gastric tumor lesions (129 patients) which were not diagnosed as
      malignancy and treated with endoscopic procedure were enrolled retrospectively.
      We compared the pretreatment endoscopic forceps biopsy results and post-treatment
      specimen biopsy results, then, analyzed the tumor characteristics. RESULTS:
      Twenty-one cases (16.3%) were diagnosed as malignancy after endoscopic treatment.
      Especially, discrepancy occurred more frequently in depressed lesions than in
      flat or elevated lesions (41.7% vs. 13.7%, p=0.012), and in lesions diagnosed as
      high grade adenomas than low or moderate grade adenomas (33.3% vs. 11.1%.
      p=0.004). CONCLUSIONS: In cases of depressed type lesions in the pretreatment
      endoscopy or those diagnosed as high grade adenoma in the pretreatment forceps
      biopsy, we should consider combined malignant lesion. Therefore, treatment
      modalities ensuring accurate diagnosis and potentially curative resection, should
      be carefully selected and performed in cases which have these features.

PMID- 22617530
TI  - Influenza A (H1N1) 2009 pandemic calm down the prevalence of acute hepatitis A in
      the latter half of 2009: Korean population study.
AB  - BACKGROUND/AIMS: There was a spiking incidence of acute hepatitis A (AHA) in 2009
      summer, but it went down drastically after an outbreak of influenza A (H1N1). We
      assessed the relationship between 2009 H1N1 pandemic and AHA prevalence from
      August to December 2009. METHODS: We compared AHA cases nationwide and in our
      hospital for the period from the latter half of 2008 to the end of 2010. H1N1
      cases in our hospital from August 2009 to December 2009 were included in the
      study and the correlation between 2009 H1N1 pandemic and AHA prevalence was
      assessed. RESULTS: The national surveillance system reported 2,233, 7,895, 15,231
      and 7,660 AHA cases from 2007 to 2010, respectively. A similar trend was noted in
      our hospital in the same periods. Although the national total incidence was
      increased in 2009, it showed steep decreasing trend line in the final 21 weeks of
      2009 (weeks 32-52), as compared with 2008 and 2010. The mean weekly incidence
      percentage (AHA cases in a week/total in a year) in weeks 32-52 of 2009 was
      1.17+/-0.55%, significantly lower than that in 2008 and 2010 (1.61+/-0.43% and
      1.56+/-0.51%; p<0.001). Furthermore, we found a significant negative correlation
      between 2009 H1N1 pandemic and AHA in our hospital for weeks 32-52 of 2009 (r=
      0.597; p<0.001). CONCLUSIONS: The widespread occurrence of 2009 H1N1 pandemic
      highlighted the benefits of health care and good hygiene, such as effective hand
      washing and wearing of masks, which may have also interrupted hepatitis A virus
      transmission.

PMID- 22617531
TI  - [A ten-year follow-up of a case with gastric adenoma accompanied with gastritis
      cystica profunda treated by endoscopic submucosal dissection].
AB  - Gastritis cystica profunda (GCP) is an uncommon hyperplastic benign lesion, and
      histologically characterized by hyperplasia and cystic dilatation of the gastric
      glands extending into the submucosal layer. GCP usually occurs at a
      gastroenterostomy site, although it can occasionally be found in an unoperated
      stomach. GCP is thought to be a possible precancerous lesion, since a few early
      gastric cancers associated with it were reported. Herein, we report a case of
      gastric adenoma associated with GCP in an unoperated patient. The sizes of both
      the GCP and adenoma overlying it have increased during a 10 year follow-up
      period. Adenoma on the latest biopsy showed low grade dysplasia, and it was
      successfully treated by endoscopic submucosal dissection.

PMID- 22617532
TI  - [Gastroduodenal intussusception due to pedunculated polypoid gastrointestinal
      stromal tumor].
AB  - The gastrointestinal stromal tumor (GIST) is a mesenchymal tumor of the digestive
      tract showing differentiation along the line of interstitial cell of Cajal. The
      most GISTs in the stomach generally show the appearance of submucosal tumors. It
      is rare for GISTs to appear as a pedunculated polypoid lesion on endoscopy. We
      experienced a case of a 51-year-old man who had a pedunculated polypoid GIST. He
      was admitted to our hospital for nausea, vomiting, melena and severe anemia
      (hemoglobin 3.4 g/dL, hematocrit 10.8%). An upper endoscopy showed gastroduodenal
      intussusception due to a pedunculated polypoid mass. This report presents a rare
      case of endoscopically proven gastroduodenal intussusceptions due to pedunculated
      polypoid GIST in the stomach.

PMID- 22617533
TI  - [A case of synchronous early gastric cancer and diffuse large B cell lymphoma
      treated with endoscopic submucosal dissection and chemotherapy].
AB  - Among malignant tumors of the stomach, adenocarcinoma takes up about 95% and the
      remaining are mostly lymphomas, being less than 5%. The majority of lymphomas are
      B cell lymphomas, and the most common types are low-grade B cell lymphoma of
      mucosa-associated lymphoid tissue and diffuse large B cell lymphoma (DLBL). The
      synchronous occurrence of adenocarcinoma and lymphoma in the stomach is being
      reported rarely. Especially the concurrence of adenocarcinoma and DLBL is very
      scarce and less than 10 cases have been reported inside and outside this country.
      In the past, the general treatment for cases of concurrence of adenocarcinoma and
      DLBL when surgery is possible according to cancer stages was gastrectomy,
      followed by single or combined chemotherapy and radiation treatment. However,
      when considering that most cases of concurrent adenocarcinoma were early gastric
      cancer which is limited to the mucosa, endoscopic submucosal dissection (ESD) can
      become an alternative treatment method for gastrectomy. We report the experience
      with chemotherapy and ESD done together instead of surgery, in patients
      concurrently diagnosed with early gastric cancer and gastric lymphoma.

PMID- 22617534
TI  - [Gastrointestinal metastasis from a primary adenocarcinoma of the lung presenting
      with acute abdominal pain].
AB  - Symptomatic gastro-intestinal metastasis in lung cancer is extremely rare and
      only a few case reports have been published. Here, we report a case with lung
      adenocarcinoma that presented with acute abdominal pain, nausea and vomiting due
      to duodenum, jejunum, and colon obstruction by the gastro-intestinal metastasis.
      The patient underwent colonoscopy and the pathologic report was adenocarcinoma.
      When there are similar histologic findings in both colon and pulmonary lesion,
      the question is whether both lesions are primary cancer or the colon lesions are
      metastases from lung cancer. Microscopic examination of a conventional pathologic
      section was not sufficient to make this determination. Immunohistochemistry was
      positive for thyroid transcription factor-1 (TTF-1) and cytokeratin 7 (CK7), and
      negative for cytokeratin 20 (CK20) and caudal-related homeobox transcription
      factor-2 (CDX-2) on colon mucosa specimen. Accordingly, we used
      immunohistochemical marker for differential diagnosis of primary adenocarcinoma
      of the lung with gastro-intestinal metastasis.

PMID- 22617535
TI  - Patient compliance with a group model of care: the hernia clinic.
AB  - BACKGROUND: In February 2006, a hernia clinic was established at the Queen
      Elizabeth II Health Sciences Centre in Halifax, Nova Scotia. It was based on a
      group model of care and was established to increase effective use of resources to
      reduce waiting times. We conducted a survey of patients referred to the hernia
      clinic to determine compliance. METHODS: We developed and mailed a questionnaire
      to all patients who had surgery after assessment at the hernia clinic. Data were
      analyzed for the entire study group and for 2 subgroups: patients in group I had
      the same surgeon for assessment and surgery, whereas patients in group II had a
      different surgeon for assessment and surgery. Differences between subgroups were
      assessed using the 2-tailed Fisher exact test. Waiting times were recorded.
      RESULTS: In all, 94 patients responded to the survey. Of these, 67% had the same
      surgeon for assessment and surgery, and 31% had a different surgeon; 2% were not
      sure. Two-thirds were comfortable having their surgery performed by a surgeon
      whom they met the day of surgery. Most patients had confidence in the competence
      of any surgeon and considered service to be better and faster in a specialized
      centre. Most felt that a group of surgeons providing hernia care uses resources
      more effectively. The waiting times from referral to initial consult decreased
      from 208 (standard deviation [SD] 139) days in 2007 to 59 (SD 70) days in 2009.
      CONCLUSION: Patient compliance with a group model of care for hernia surgery is
      high.

PMID- 22617536
TI  - Results of en bloc resection for hepatocellular carcinoma extending to adjacent
      organs.
AB  - BACKGROUND: To curatively resect hepatocellular carcinoma (HCC) with adjacent
      organ extension, the combined resection of these organs is inevitable. We
      analyzed the safety and effectiveness of en bloc resection for HCC extending to
      adjacent organs. METHODS: From December 2002 to May 2006, we compared the
      surgical outcomes of patients with HCC extending to adjacent organs with those of
      closely matched, randomly selected patients with HCC without adjacent organ
      extension. RESULTS: We included 42 patients whose HCC extended to adjacent organs
      and 126 patients whose HCC did not extend to adjacent organs. There was no
      significant difference in survival, operative morbidity or mortality between the
      groups. In patients with HCC extending to adjacent organs, histopathological
      examination of the specimen revealed true tumour invasion in 13 and adhesion in
      29 patients. Those with tumour invasion were more likely to have a high incidence
      of capsule infiltration, microvascular invasion and early intrahepatic recurrence
      (<= 1 yr after hepatectomy). The 5-year overall survival of patients with tumour
      invasion was 11.5%, whereas that of patients with tumour adhesion was 38.1% (p =
      0.033). CONCLUSION: En bloc resection is a safe and effective therapy for HCC
      extending to adjacent organs. Tumour invasion to adjacent organs exhibits a more
      aggressive clinical behaviour and is associated with worse survival than tumour
      adhesion.

PMID- 22617537
TI  - Morbidity of hand-assisted laparoscopic splenectomy compared to conventional
      laparoscopic splenectomy: a 6-year review.
AB  - BACKGROUND: Laparoscopic splenectomy (LS) has several advantages over the open
      procedure but can be technically demanding when performed in patients with
      massive splenomegaly. We hypothesized that patients who undergo hand-assisted LS
      (HALS) may experience the benefits of LS while having their enlarged spleens
      removed safely. METHODS: We reviewed the charts of patients who underwent HALS or
      LS between January 2003 and June 2008. Evaluated parameters included
      intraoperative and early postoperative morbidity and mortality, conversion to
      open surgery, need for blood transfusion, length of postoperative hospital stay,
      patient demographics, diagnosis leading to splenectomy, splenic weight and number
      of postoperative days to resuming normal diet. Differences were analyzed while
      controlling for splenic weight and malignant diagnosis using multiple linear and
      logistic regression analysis. RESULTS: In all, 103 patients underwent splenectomy
      (23 HALS, 80 LS). Patients who had HALS were older and had larger spleens, and a
      greater proportion had malignant diagnoses. We observed no significant
      differences in morbidity, conversion to open surgery or need for blood
      transfusion. The mean length of postoperative stay, duration of surgery and days
      to resuming full diet were longer in the HALS group. No patients died. No group
      differences were significant after controlling for splenic weight and malignant
      diagnosis. CONCLUSION: The morbidity associated with HALS is comparable to that
      with LS. The longer duration of surgery and hospital stay for HALS patients was
      likely related to greater splenic weight, older age and greater proportion of
      malignant diagnoses. Hand-assisted LS is a viable alternative to open surgery in
      patients with massive spleens.

PMID- 22617538
TI  - Predictors of attrition in a multidisciplinary adult weight management clinic.
AB  - BACKGROUND: Worldwide, more than 1.7 billion individuals may be classified as
      overweight and are in need of appropriate medical and surgical treatments. The
      primary goal of a comprehensive weight management program is to produce
      sustainable weight loss. However, for such a program to be effective, the patient
      must complete it. We analyzed attrition rates and predictors of attrition within
      a publicly funded, multidisciplinary adult weight management program. METHODS: We
      retrospectively reviewed charts from an urban multidisciplinary adult weight
      management clinic program database. Patients received medical or surgical
      treatment with appropriate follow-up. We collected information on demographics
      and comorbidities. Patients in the surgical clinics received either laparoscopic
      gastric band insertion or gastric bypass. We conducted univariate analysis and
      multivariate analyses on predictors of attrition. RESULTS: A total of 1205
      patients were treated in the weight management program: 887 in the medical clinic
      and 318 with surgery and follow-up in a surgical clinic. Overall, 516 patients
      left the program or were lost to follow-up (attrition rate 42.8%). The attrition
      rate was 53.9% in the medical clinic and 11.9% in the surgical clinic.
      Multivariate analyses identified participation in the medical clinic, younger
      patient age and lower body mass index as predictors of attrition. CONCLUSION: We
      found lower attrition rates among surgically than medically treated patients in a
      multidisciplinary weight management clinic. Further research is needed to
      understand those variables that lead to improved attrition rates.

PMID- 22617539
TI  - Treatment of hepatic hydatid disease complications using endoscopic retrograde
      cholangiopancreatography procedures.
AB  - BACKGROUND: Liver hydatidosis may lead to serious morbidity due to biliary
      complications, the management for which endoscopic sphincterotomy (ES) and
      biliary drainage are very efficient. We evaluated the effectiveness of endoscopic
      treatment for complications of hepatic hydatid disease. METHODS: We
      retrospectively reviewed endoscopic retrograde cholangiopancreatography (ERCP)
      procedures performed between January 2000 and December 2009 and compared
      laboratory findings, localization of the lesions and ERCP procedures applied
      between patients with and without jaundice. RESULTS: In all, 70 ERCP procedures
      were performed in 54 patients (24 men, 30 women). Of the 70 procedures, 24 were
      performed to treat jaundice. All patients with biliary fistulas and jaundice were
      managed with endoscopic procedures. The 70 ERCP procedures included
      sphincterotomy only (n = 40); sphincterotomy and stent placement (n = 7); stent
      placement only (n = 4); sphincterotomy and membrane extraction (n = 9);
      sphincterotomy, membrane extraction and pus drainage (n = 5); and sphincterotomy
      and pus drainage (n = 5). Laboratory results improved in 3-7 days, and bile
      leakage ceased in 2-21 days. CONCLUSION: Endoscopic retrograde
      cholangiopancreatography is a safe and effective way to manage biliary
      complications of hepatic echinococcal disease. In most patients, ES is the most
      efficient treatment of postoperative external biliary fistulas, jaundice and
      accompanying cholangitis, as it enables clearing the bile ducts of hydatid
      remnants; ES should be performed since it accelerates the healing process by
      decreasing pressure in the choledochus.

PMID- 22617540
TI  - Retrospective review of all-terrain vehicle accidents in Alberta.
AB  - BACKGROUND: All-terrain vehicles (ATVs) are frequently associated with injuries
      and deaths. In spite of this, very few guidelines, let alone legal restrictions,
      exist to guide users of these machines. METHODS: We conducted a standardized
      review of prospectively collected data from the Alberta Trauma Registry. All
      patients who were involved in ATV-related traumas from 2003 to 2008 with an
      Injury Severity Score (ISS) greater than 12 were included. The variables studied
      were age, sex, type of vehicle, purpose of use, person injured (driver or
      passenger), ISS, distribution of injuries, length of hospital stay, helmet use
      and death. RESULTS: We evaluated 435 patients with ATV-related injuries and ISS
      greater than 12. The average ISS was 22.8, with an overall mortality of 4.6%; 55%
      of patients were not wearing helmets, and most of the deaths (85%) occurred among
      these individuals. Helmet use was associated with a lower risk of mechanical
      ventilation and of injury to the head and/or cervical spine. Children accounted
      for 18.9% of all patients and 15% of deaths; 57% of them were wearing helmets at
      the time of their accidents. CONCLUSION: All-terrain vehicle use in Alberta
      carries a significant risk of injury and death, and there is an association
      between death and lack of helmet use. A minimum age for ATV use of at least 16
      years and a legal requirement for helmet use may increase public awareness of
      these risks and decrease morbidity and mortality.

PMID- 22617541
TI  - Surgical site infection prevention: a survey to identify the gap between evidence
      and practice in University of Toronto teaching hospitals.
AB  - BACKGROUND: A gap exists between the best evidence and practice with regards to
      surgical site infection (SSI) prevention. Awareness of evidence is the first step
      in knowledge translation. METHODS: A web-based survey was distributed to 59
      general surgeons and 68 residents at University of Toronto teaching hospitals.
      Five domains pertaining to SSI prevention with questions addressing knowledge of
      prevention strategies, efficacy of antibiotics, strategies for changing practice
      and barriers to implementation of SSI prevention strategies were investigated.
      RESULTS: Seventy-six individuals (60%) responded. More than 90% of respondents
      stated there was evidence for antibiotic prophylaxis and perioperative
      normothermia and reported use of these strategies. There was a discrepancy in the
      perceived evidence for and the self-reported use of perioperative hyperoxia,
      omission of hair removal and bowel preparation. Eighty-three percent of
      respondents felt that consulting published guidelines is important in making
      decisions regarding antibiotics. There was also a discrepancy between what
      respondents felt were important strategies to ensure timely administration of
      antibiotics and what strategies were in place. Checklists, standardized orders,
      protocols and formal surveillance programs were rated most highly by 75%-90% of
      respondents, but less than 50% stated that these strategies were in place at
      their institutions. CONCLUSION: Broad-reaching initiatives that increase surgeon
      and trainee awareness and implementation of multifaceted hospital strategies that
      engage residents and attending surgeons are needed to change practice.

PMID- 22617543
TI  - Evaluation of the effects of low temperature on performance of standard non
      electric medical equipment at -21.5 degrees C (-6.7 degrees F) - a descriptive
      study on a real life challenge in the prehospital setting.
AB  - AIM OF THE STUDY: To our knowledge, there are no previous reports on the
      performance of medical equipment in cold conditions. The aim of this study was to
      evaluate the performance of several plastic, single-use medical equipment exposed
      to cold outdoor temperature. METHODS: Medical equipment such as endotracheal
      tubes, suction catheters and intravenous lines were exposed to outdoor
      temperature of -21.5 degrees C (-6.7 degrees F) for 15 min. After 15 min the
      equipment underwent a manual stress test resembling normal prehospital use.
      RESULTS: After 15 min in -21.5 degrees C (-6.7 degrees F) during the stress test
      several equipment exhibited significant changes in properties as compared to room
      temperature. Mainly, loss of flexibility and connectivity was observed. Examples
      of these were fractures of endotracheal tubes and suction catheters, and
      permanent airway adapter loosening from a respirator breathing circuit.
      CONCLUSION: Plastic medical equipment has poor tolerance of cold conditions. Loss
      of equipment performance and properties could result in relevant harm to the
      patient. Retaining the equipment, e.g. in a closed backpack slows the rate of
      temperature decrease.

PMID- 22617542
TI  - Late conversion of endovascular to open repair of abdominal aortic aneurysms.
AB  - BACKGROUND: Failure of endovascular repair (EVAR) of an abdominal aortic aneurysm
      can result in significant risk of morbidity and mortality. We review our
      experience with late conversions to open repair. METHODS: We conducted a
      retrospective database review to identify all EVAR procedures performed between
      1997 and 2010 and the number converted to open repair at our university
      affiliated medical centre. Late conversion was defined as those occurring at
      least 30 days after initial EVAR. RESULTS: In all, 892 EVARs took place during
      the study period. Six patients (0.7%) required late conversion to open repair.
      Their mean age was 71 (range 58-83) years, and half were women. Half of the
      initial EVARs were for ruptured aneurysms. The median time to conversion was 15.6
      (range 1.7-61.3) months. Indications for secondary conversion (50% urgent, 50%
      elective) included persistent type I endoleak (n = 3), combined type II and III
      endoleak (n = 1), graft thrombosis (n = 1) and aneurysm rupture (n = 1).
      Supraceliac clamping was required in most patients (67%), and the mean
      transfusion requirement was 2.6 units. Total endograft explantation occurred in 2
      patients (33%), whereas partial or total endograft preservation occurred in 4
      (67%). Median length of stay in hospital after conversion was 7 (range 6-73)
      days. There were no instances of early or in-hospital mortality following
      conversion. CONCLUSION: Our EVAR experience includes a low rate of late
      conversion to open repair, with most conversions being a result of persistent
      aneurysm perfusion. Although technically challenging, late conversion can be
      safe. Our experience supports ongoing surveillance after EVAR.

PMID- 22617544
TI  - Sedimentation equilibria of ferrofluids: II. Experimental osmotic equations of
      state of magnetite colloids.
AB  - The first experimental osmotic equation of state is reported for well-defined
      magnetic colloids that interact via a dipolar hard-sphere potential. The osmotic
      pressures are determined from the sedimentation equilibrium concentration
      profiles in ultrathin capillaries using a low-velocity analytical centrifuge,
      which is the subject of the accompanying paper I. The pressures of the magnetic
      colloids, measured accurately to values as low as a few pascals, obey Van 't
      Hoff's law at low concentrations, whereas at increasing colloid densities non
      ideality appears in the form of a negative second virial coefficient. This virial
      coefficient corresponds to a dipolar coupling constant that agrees with the
      coupling constant obtained via independent magnetization measurements. The
      coupling constant manifests an attractive potential of mean force that is
      significant but yet not quite strong enough to induce dipolar chain formation.
      Our results disprove van der Waals-like phase behavior of dipolar particles for
      reasons that are explained.

PMID- 22617545
TI  - Shortfalls in published neurosurgical literature.
AB  - Expenditure related to neurosurgery has increased unevenly since the early 1990s.
      In this study we explored the literature by which clinical evidence is obtained
      to better direct neurosurgical practice. We searched different types of
      neurosurgery literature and four major neurosurgical procedures (excision of
      brain lesion, cerebral aneurysm clipping/coiling, discectomy, spine fusion)
      written in English on PubMed from 1996, the year of its launch, using the keyword
      "cost". Only a small and static portion of the neurosurgical literature was
      indexed as level I clinical evidence (randomized controlled trials), with a lack
      of cost appraisal in the outcome analysis of neurosurgical interventions. By way
      of rectification, a major increase in funding of grade I studies with cost
      analysis, and the requirement by peer-reviewed journals of a cost-benefit
      analysis, would promote the quality of clinical research yielding unquestionable
      advantage on national healthcare practice.

PMID- 22617546
TI  - TRPV4 axonal neuropathy spectrum disorder.
AB  - The TRPV4-axonal neuropathy spectrum is a group of disorders presenting as a
      predominantly motor axonal peripheral neuropathy, frequently in association with
      vocal cord paralysis, and occasionally accompanied by sensorineural hearing loss
      and bladder urgency and incontinence. These disorders show autosomal dominant
      inheritance, variable disease expression and reduced disease penetrance. TRPV4
      encodes a calcium-permeable non-selective cation channel of uncertain biological
      function. Intriguingly, mutations in this gene also underlie a family of
      autosomal dominant, short-stature skeletal dysplasias. This article reviews the
      clinical features of the neuropathy spectrum, the emerging neuropathy/skeletal
      dysplasia overlap disorders and the present knowledge of the impact of mutations
      in this gene on channel function.

PMID- 22617547
TI  - A genetic diagnostic approach to infantile epileptic encephalopathies.
AB  - Epileptic encephalopathies are characterized by frequent severe seizures, and/or
      prominent interictal epileptiform discharges on the electroencephalogram,
      developmental delay or deterioration, and usually a poor prognosis. The
      epileptiform abnormalities themselves are believed to contribute to the
      progressive disturbance in cerebral function. Determining the underlying
      aetiology responsible for infantile epileptic encephalopathy is a clinical
      challenge worth undertaking to facilitate advice on the recurrence risk and to
      allow for the option of prenatal testing, as often this category of epilepsy is
      associated with devastating hardship for families. This review takes advantage of
      recently published studies that have identified new genes associated with
      epilepsy and focuses on known monogenic causes where detection is useful for the
      process of genetic counselling. Based on the review, we present a diagnostic work
      up in order to triage specific genetic testing for infants presenting with an
      epileptic encephalopathy.

PMID- 22617548
TI  - Quantitative analysis of random migration of cells using time-lapse video
      microscopy.
AB  - Cell migration is a dynamic process, which is important for embryonic
      development, tissue repair, immune system function, and tumor invasion (1, 2).
      During directional migration, cells move rapidly in response to an extracellular
      chemotactic signal, or in response to intrinsic cues (3) provided by the basic
      motility machinery. Random migration occurs when a cell possesses low intrinsic
      directionality, allowing the cells to explore their local environment. Cell
      migration is a complex process, in the initial response cell undergoes
      polarization and extends protrusions in the direction of migration (2).
      Traditional methods to measure migration such as the Boyden chamber migration
      assay is an easy method to measure chemotaxis in vitro, which allows measuring
      migration as an end point result. However, this approach neither allows
      measurement of individual migration parameters, nor does it allow to
      visualization of morphological changes that cell undergoes during migration.
      Here, we present a method that allows us to monitor migrating cells in real time
      using video - time lapse microscopy. Since cell migration and invasion are
      hallmarks of cancer, this method will be applicable in studying cancer cell
      migration and invasion in vitro. Random migration of platelets has been
      considered as one of the parameters of platelet function (4), hence this method
      could also be helpful in studying platelet functions. This assay has the
      advantage of being rapid, reliable, reproducible, and does not require
      optimization of cell numbers. In order to maintain physiologically suitable
      conditions for cells, the microscope is equipped with CO(2) supply and
      temperature thermostat. Cell movement is monitored by taking pictures using a
      camera fitted to the microscope at regular intervals. Cell migration can be
      calculated by measuring average speed and average displacement, which is
      calculated by Slidebook software.

PMID- 22617549
TI  - Three new azaphilones produced by a marine fish-derived chaetomium globosum.
AB  - Three new metabolites, chaetomugilin S, dechloro-chaetomugilin A and dechloro
      chaetomugilin D, were isolated from a strain of Chaetomium globosum originally
      obtained from the marine fish Mugil cephalus, and their absolute stereostructures
      were elucidated based on the basis of spectroscopic analyses, including 1D and 2D
      NMR techniques and some chemical transformations. Particularly, chaetomugilins T
      and U are the first compounds without a chlorine atom in azaphilones isolated
      from this fungal strain, to date. In addition, these compounds moderately
      inhibited the growth of cultured P388, HL-60, L1210 and KB cell lines.

PMID- 22617550
TI  - A novel acyclic oligomycin A derivative formed via retro-aldol rearrangement of
      oligomycin A.
AB  - The antibiotic oligomycin A in the presence of K(2)CO(3) and n-Bu(4)NHSO(4) in
      chloroform in phase-transfer conditions afforded a novel derivative through the
      initial retro-aldol fragmentation of the 8,9 bond, followed by further
      transformation of the intermediate aldehyde. NMR, MS and quantum chemical
      calculations showed that the novel compound is the acyclic oligomycin A
      derivative, in which the 8,9 carbon bond is disrupted and two polyfunctional
      branches are connected with spiroketal moiety in positions C-23 and C-25. The tri
      O-acetyl derivative of the novel derivative was prepared. The acyclic oligomycin
      A derivative retained the ability to induce apoptosis in tumor cells at low
      micromolar concentrations, whereas its antimicrobial potencies decreased
      substantially. The derivative virtually lost the inhibitory activity against
      F(0)F(1) ATP synthase-containing proteoliposomes, strongly suggesting the
      existence of the target(s) beyond F(0)F(1) ATP synthase that is important for the
      antitumor potency of oligomycin A.

PMID- 22617551
TI  - The bla(CTX-M) gene independently enhances drug resistance level to ampicillin in
      clinical isolates of Klebsiella pneumoniae.

PMID- 22617552
TI  - Health and access to care among employed and unemployed adults: United States,
      2009-2010.
AB  - Lack of health insurance has been shown to be associated with problems obtaining
      needed health care (3), and the unemployed are less likely to have health
      insurance than are their employed counterparts. The number and rate of adults
      aged 18-64 years lacking health insurance has been increasing, in part due to the
      historically high unemployment rates. However, even having comprehensive health
      insurance coverage does not guarantee access to needed services, in part because
      of cost-sharing, including copayments and deductibles. Unemployed persons may
      retain their health insurance through the Consolidated Omnibus Budget
      Reconciliation Act (COBRA) or through other programs, but COBRA payments in
      particular may be quite expensive, and individual insurance plans may be less
      comprehensive than many employer-sponsored plans (4). Thus, although some
      unemployed adults may retain coverage for some period of time, they may be less
      able to meet cost-sharing requirements because of reduced income associated with
      unemployment. This analysis compares the health status and access to care of
      employed and unemployed adults and shows that unemployment is associated with
      unfavorable health and access to care among adults in the labor force over and
      above the loss of health insurance. However, it is not possible to know from
      these data the extent to which unemployment is a cause or effect of poor health.
      Poor health may be both a cause and effect of unemployment. Adults with private
      health insurance were more likely to have serious psychological distress and
      respondent-reported fair or poor health status if they were unemployed. In fact,
      unemployed privately insured persons were more than three times as likely to have
      serious psychological distress as their employed counterparts. Similar patterns
      were found for adults with public insurance and no health insurance. There were
      no significant differences between employed and unemployed adults in the
      percentage who had ever been diagnosed with selected chronic conditions,
      including hypertension, heart disease, diabetes, or cancer (NCHS unpublished
      analysis of NHIS data), and so the need for health care to treat these chronic
      conditions exists for both employed and unemployed adults. In addition to having
      poorer health, unemployed adults were more likely to delay or not receive needed
      medical care and needed prescriptions due to cost than their employed
      counterparts across categories of insurance coverage. Thus, the unemployed
      reported both worse health and less access to needed care and treatment than
      employed adults. This pattern was found not only for those without health
      insurance but also those with public and private insurance.

PMID- 22617553
TI  - Letter from the editor.

PMID- 22617555
TI  - The hospitalized prisoner with a life-threatening illness: criminal first and
      patient second?
AB  - It is generally accepted that the Patient's Bill of Rights applies to all
      patients including prisoners. Yet, a prisoners' incarcerated status generally
      prohibits inmates from making any decision that may shorten his/her life, and as
      such, the de facto medical decision maker becomes the medical director of the
      state correctional facility. This case study highlights the challenges that arise
      when the ethically appropriate response to a hospitalized prisoner's terminal
      medical condition warrants decisions that are in conflict with that advocated by
      the correctional facility.

PMID- 22617556
TI  - Remediation: a necessary function for employers to correct incompetence regarding
      clinical professional registered nurse practice.
AB  - Remediation for the professional licensed registered nurse is a topic sparsely
      written about in the nursing literature. The provision of remediation, however,
      is a common tool used to address registered nurse practice issues. This article
      seeks to describe the various stakeholders' roles in remediation and recommends
      that nurses in management roles should ensure the provision of remediation for
      registered nurses when warranted.

PMID- 22617558
TI  - A comparative of Magnet(r) organizations and accountable care organizations.
AB  - While Magnet(r) is a commitment to excellence and thus recognition, the
      accountable care organization (ACO) focus is to quality and reimbursement. Each
      can be built on a model of shared characteristics that in the end will prove a
      source of success for the creation of an organization that is both an ACO and
      Magnet. In an effort to align strategic initiatives as synergistic processes, not
      competing priorities, 10 shared characteristics of Magnet organizations and ACOs
      are presented.

PMID- 22617559
TI  - Genetic-related and carbohydrate-related factors affecting liver fat
      accumulation.
AB  - PURPOSE OF REVIEW: To summarize recent findings that have examined dietary,
      genetic and gene-diet interactions that contribute to fat accumulation in the
      liver during growth and development, with particular focus on contributions
      relating to dietary carbohydrate and sugar consumption. In addition, this review
      highlights how some of these contributions to liver fat vary across the
      population in terms of ethnic-specific effects. RECENT FINDINGS: Dietary
      carbohydrate, and especially sugars contribute to increased liver fat
      accumulation due to the lipogenic potential of fructose during liver metabolism.
      In addition, recent genome-wide studies have identified several polymorphisms
      that contribute to increased liver fat accumulation, with some of these genes
      relating to dietary carbohydrate and sugar consumption. In particular, the
      patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene, which is
      highly prevalent in Hispanics, contributes to excessive liver fat beginning at a
      young age, especially in the context of high sugar consumption. SUMMARY: Dietary
      sugar contributes to liver fat accumulation, with this being explained by de-novo
      lipogenesis from fructose in the liver. Certain genetic factors, including
      PNPLA3, glucokinase regulatory protein and APOC3 contribute to increased liver
      fat accumulation, with these effects being manifested at an early age. Hispanics
      in particular are at elevated risk for liver fat accumulation because of the
      higher frequency of genetic variants such as PNPLA3 and glucokinase regulatory
      protein as well as an interaction between the PNPLA3 and dietary sugar.

PMID- 22617560
TI  - Regulation of low-density lipoprotein subfractions by carbohydrates.
AB  - PURPOSE OF REVIEW: This article aims at reviewing the recent findings that have
      been made concerning the crosstalk of carbohydrate metabolism with the generation
      of small, dense low-density lipoprotein (LDL) particles, which are known to be
      associated with an adverse cardiovascular risk profile. RECENT FINDINGS: Studies
      conducted during the past few years have quite unanimously shown that the
      quantity of carbohydrates ingested is associated with a decrease of LDL particle
      size and an increase in its density. Conversely, diets that aim at a reduction of
      carbohydrate intake are able to improve LDL quality. Furthermore, a reduction of
      the glycaemic index without changing the amount of carbohydrates ingested has
      similar effects. Diseases with altered carbohydrate metabolism, for example, type
      2 diabetes, are associated with small, dense LDL particles. Finally, even the
      kind of monosaccharide the carbohydrate intake consists of is important
      concerning LDL particle size: fructose has been shown to alter the LDL particle
      subclass profile more adversely than glucose in many recent studies. SUMMARY: LDL
      particle quality, rather than its quantity, is affected by carbohydrate
      metabolism, which is of clinical importance, in particular, in the light of
      increased carbohydrate consumption in today's world.

PMID- 22617561
TI  - DNA methylation and hepatic insulin resistance and steatosis.
AB  - PURPOSE OF REVIEW: In this review, we show novel evidence about the role of the
      liver in the development of insulin resistance and suggest that abnormal hepatic
      triglyceride accumulation is not an innocent bystander comorbidity but adversely
      affects the peripheral insulin sensitivity. RECENT FINDINGS: The core of this
      review is built up around the concept that liver DNA methylation of the
      peroxisome proliferative activated receptor gamma coactivator one alpha gene
      promoter modulates the status of peripheral insulin resistance and is strongly
      associated with plasma fasting insulin levels. We discuss about other mechanisms
      associated with peroxisome proliferative activated receptor gamma coactivator one
      alpha regulation, such as an acetylation and deacetylation switch and how these
      events impact on the liver metabolic function. We suggest a mitochondrial-centric
      approach to understand the connection between nonalcoholic fatty liver disease
      and insulin resistance. We finally show new data about how the liver epigenome is
      modulated by nutritional cues and introduce the role of epigenetics in liver
      metabolic programming. SUMMARY: The implications of these findings for clinical
      practice are promising, as the inherent plasticity of epigenetic modifications,
      produced either physiologically or pathologically, suggests that early
      therapeutic intervention in patients with fatty liver can potentially revert the
      systemic phenotype associated with insulin resistance.

PMID- 22617562
TI  - Epigenetic regulation of adipogenesis.
AB  - PURPOSE OF REVIEW: Epigenetic regulation plays an essential role in cell
      differentiation, by allowing the establishment and maintenance of the gene
      expression pattern of the mature cell type. Because of its importance in chronic
      diseases, adipogenesis is one of the best-studied differentiation processes. The
      hormonal and transcriptional cascades governing the differentiation of the
      adipocytes are well known, but the role of epigenetic mechanisms is only starting
      to emerge. In this review, we intend to summarize the recently described
      epigenetic events that participate in adipogenesis and their connections with the
      main factors that constitute the classical transcriptional cascade. RECENT
      FINDINGS: The advent of high-throughput technologies has made possible the
      exhaustive analysis of the epigenetic phenomenons taking place during
      adipogenesis. The cooperative recruitment of CCAAT/enhancer-binding protein
      (C/EBPbeta) and other early proadipogenic transcription factors to transcription
      factor hotspots shortly after induction of adipogenesis is required to establish
      a transient epigenomic state that then informs the recruitment of the later
      adipogenic transcription factors peroxisome proliferator-activated receptor
      (PPARgamma) and C/EBPalpha to their target genes. SUMMARY: Epigenetic marks and
      chromatin-modifying proteins contribute to adipogenesis and, through regulation
      of the phenotypic maintenance of the mature adipocytes, to the control of
      metabolism.

PMID- 22617563
TI  - Epigenetics and eating disorders.
AB  - PURPOSE OF REVIEW: Eating disorders are complex psychiatric disorders in which
      genes, environment, and gene-environment interactions (G*E) have a role. Such G*E
      may occur in adulthood or during development. They may also be modified by
      factors such as (mal)nutrition or stress and this may result in acute or long
      term epigenetic modifications. This review discusses the potential for recent
      developments in epigenetics to address ongoing aetiological issues in eating
      disorders. RECENT FINDINGS: Epigenetic studies in eating disorders have focussed
      on the DNA methylation status of promoter regions of candidate genes: differences
      have been reported between people with eating disorders and healthy controls, and
      between subtypes of eating disorders. Animal studies related to eating disorders
      have focussed on understanding the acute and long-term effects of environmental
      manipulation on epigenetic changes and on the resultant phenotypes: these studies
      are promising, but they have also identified some of the complexity of epigenetic
      processing. SUMMARY: Because of the difficulties in obtaining brain samples,
      epigenetic studies in eating disorders (like in other psychiatric illnesses) have
      used peripheral tissues, usually blood: this raises various problems. It is
      likely, therefore, that in the immediate future, animal, rather than human
      studies will guide the progress in epigenetics studies of eating disorders and
      other psychiatric disorders.

PMID- 22617564
TI  - Low-carbohydrate ketogenic diets, glucose homeostasis, and nonalcoholic fatty
      liver disease.
AB  - PURPOSE OF REVIEW: Obesity-associated nonalcoholic fatty liver disease (NAFLD) is
      highly prevalent, for which weight loss is the generally recommended clinical
      management. Low-carbohydrate ketogenic diets have been successful in promoting
      weight loss, but variations in the range of metabolic responses to these diets
      indicate that the effects of altering macronutrient content are not completely
      understood. This review focuses on the most recent findings that reveal the
      relationship between low-carbohydrate diets and NAFLD in rodent models and
      humans. RECENT FINDINGS: Low-carbohydrate diets have been shown to promote weight
      loss, decrease intrahepatic triglyceride content, and improve metabolic
      parameters of patients with obesity. These ketogenic diets also provoke weight
      loss in rodents. However, long-term maintenance on a ketogenic diet stimulates
      the development of NAFLD and systemic glucose intolerance in mice. The
      relationship between ketogenic diets and systemic insulin resistance in both
      humans and rodents remains to be elucidated. SUMMARY: Because low-carbohydrate
      ketogenic diets are increasingly employed for treatment of obesity, NAFLD, and
      neurological diseases such as epilepsy, understanding the long-term systemic
      effects of low-carbohydrate diets is crucial to the development of efficacious
      and safe dietary interventions.

PMID- 22617565
TI  - Role of fibroblast growth factor 19 in the control of glucose homeostasis.
AB  - PURPOSE OF REVIEW: Fibroblast growth factor 19 (FGF19) is a postprandial hormone
      released from the small intestine. FGF19 improves glucose tolerance when
      overexpressed in mice with impaired glucose tolerance or diabetes. This review
      summarizes the recent advances in our understanding of the biology of FGF19 and
      its role in glucose homeostasis, with emphasis on publications from 2010 to 2012.
      RECENT FINDINGS: Protein engineering was used to generate FGF19 protein variants
      that allowed the separation of its mitogenic and metabolic functions. Its cognate
      receptor in the liver (FGFR4) mediated the effects of FGF19 on proliferation and
      bile salt synthesis, while this receptor was dispensable for its effects on
      glucose homeostasis. New metabolic activities of FGF19 were uncovered. FGF19
      signaling was shown to stimulate glycogen and protein synthesis, and inhibit
      gluconeogenesis. FGF19 employed signaling routes distinct from those used by
      insulin to regulate these pathways. Mice with genetic disruption of Fgf15 (the
      mouse FGF19 ortholog) were glucose intolerant but had normal insulin levels and
      normal insulin sensitivity. Reduced hepatic glycogen stores and elevated hepatic
      gluconeogenesis were observed in the knock-out mice under the conditions in which
      insulin signaling was active. SUMMARY: FGF19 signaling regulates glucose
      homeostasis in mice. The (patho)physiological role of FGF19 in glucose
      homeostasis in humans remains to be determined. Its novel insulin-mimetic
      actions, combined with the elimination of its mitogenic activity by protein
      engineering, make FGF19 an attractive candidate for the treatment of type 2
      diabetes.

PMID- 22617566
TI  - Fructose toxicity:  is the science ready for public health actions?
AB  - PURPOSE OF REVIEW: The assumption that fructose may be toxic and involved in the
      pathogenesis of noncommunicable diseases such as obesity, diabetes mellitus,
      dyslipidemia, and even cancer has resulted in the call for public health action,
      such as introducing taxes on sweetened beverages. This review evaluates the
      scientific basis for such action. RECENT FINDINGS: Although some studies hint
      towards some potential adverse effects of excessive fructose consumption
      especially when combined with excess energy intake, the results from clinical
      trials do not support a significant detrimental effect of fructose on metabolic
      health when consumed as part of a weight-maintaining diet in amounts consistent
      with the average-estimated fructose consumption in Western countries. However,
      definitive studies are missing. SUMMARY: Public health policies to eliminate or
      limit fructose in the diet should be considered premature. Instead, efforts
      should be made to promote a healthy lifestyle that includes physical activity and
      nutritious foods while avoiding intake of excess calories until solid evidence to
      support action against fructose is available. Public health is almost certainly
      to benefit more from policies that are aimed at promoting what is known to be
      good than from policies that are prohibiting what is not (yet) known to be bad.

PMID- 22617568
TI  - Catalase polymorphisms and metabolic diseases.
AB  - PURPOSE OF REVIEW: This review summarizes our current understanding of the
      implication of catalase polymorphisms in the occurrence, control and
      comorbidities of metabolic diseases. RECENT FINDINGS: Whatever impaired glucose
      tolerance, insulin resistance on diabetes and whatever their occurrence or
      implications, the studies taken together converge toward the hypothesis that
      catalase polymorphisms play a role in glucose disorders. -262C/T and -844A>G
      single nucleotide polymorphisms are associated to hypertension susceptibility
      and/or onset. Concerning dyslipidemia, very recent studies requiring confirmation
      report a -262C/T implication. Finally, a role of catalase polymorphisms in bone
      metabolism is described. SUMMARY: Plethora of studies on catalase SNPs and their
      link with diseases exist. It is now clear that genetic variations in the catalase
      gene and its promoter are putative risk factors for metabolic disease. The
      question of how these polymorphisms actively play a role in various metabolisms
      remains unanswered. Further functional studies are required in order to gain a
      deeper insight into the direct role of catalase.

PMID- 22617567
TI  - Clock regulation of dietary lipid absorption.
AB  - PURPOSE OF REVIEW: To summarize the new knowledge about the regulation of dietary
      lipid absorption by circadian locomotor output cycles kaput (Clock) and
      Nocturnin. RECENT FINDINGS: Recent findings have shown that Clock and Nocturnin,
      proteins involved in circadian regulation, play an important role in the
      regulation of dietary lipid absorption. Clock deficiency increases, whereas
      Nocturnin deficiency decreases lipid absorption. Clock plays a role in turning
      off the genes involved in lipid absorption at the onset of the day. Molecular
      studies revealed that Clock binds to the promoter of small heterodimer partner to
      enhance its transcription. When levels are high, small heterodimer partner
      interacts with the transcription factors associated with the promoter of
      microsomal triglyceride transfer protein to repress transcription. Reduced
      microsomal triglyceride transfer protein levels are correlated with low
      intestinal lipid absorption and plasma lipid levels. In contrast, Nocturnin
      assists in lipid absorption by regulating their partitioning in different
      intracellular compartments. SUMMARY: Clock and Nocturnin regulate lipid
      absorption involving different mechanisms. It is likely that other clock genes
      also modulate lipid absorption and plasma lipid levels.

PMID- 22617569
TI  - Osteoblastoma of mandible.

PMID- 22617570
TI  - Cosmetic gynecology and the elusive quest for the "perfect" vagina.

PMID- 22617571
TI  - The new-generation tuberculosis test: should it be used in pregnancy?

PMID- 22617572
TI  - Number of cervical examinations and risk of intrapartum maternal fever.
AB  - OBJECTIVE: To estimate the association between number of cervical examinations
      and risk of maternal fever during term labor and delivery. METHODS: Within a 4
      year retrospective cohort study of all consecutive term (37 weeks of gestation or
      more) singleton deliveries reaching the second stage of labor, we identified
      women who developed an intrapartum fever and compared them with women who
      remained afebrile through 6 hours postpartum. Primary exposure was number of
      digital cervical examinations. Extensive data were collected from the medical
      record, including obstetric and medical history, cervical examinations and
      timing, admitting diagnoses, and outcomes. Time-to-event analyses were used to
      account for length of labor. Cox proportional hazard models were developed
      adjusting for potentially confounding factors. RESULTS: Of 2,395 women who were
      afebrile at admission, 174 (7.2%) developed an intrapartum fever. Women were
      examined one to 14 times. There was no significant association between increasing
      number of examinations and risk of fever. Even for the 505 women who had more
      than seven examinations during labor, there was no statistically significant
      increased risk of fever (hazard ratio 0.9, 95% confidence interval 0.4-2.0)
      compared with those with one to three examinations. Subanalyses by labor type and
      examinations after rupture of membranes also showed no significant association
      between number of cervical examinations and risk of intrapartum fever.
      CONCLUSION: During term labor management, maternal fever risk is not
      significantly increased by the number of cervical examinations. LEVEL OF
      EVIDENCE: II.

PMID- 22617573
TI  - Limited course of antibiotic treatment for chorioamnionitis.
AB  - OBJECTIVE: We sought to estimate the effectiveness of a limited course of
      antibiotics in treating patients with chorioamnionitis. METHODS: We conducted a
      retrospective review of patients treated for chorioamnionitis at our medical
      center from 2005 to 2009. Patients received ampicillin plus gentamicin as soon as
      the diagnosis was made. Postpartum they received only the next scheduled dose of
      each antibiotic. Patients who underwent a cesarean delivery received either
      metronidazole or clindamycin immediately after cord clamping. The primary outcome
      was treatment failure, defined as persistent fever requiring continuation of
      antibiotics, surgical intervention, or administration of heparin. RESULTS: Of the
      423 patients, 282 delivered vaginally, and 141 delivered by cesarean. Overall,
      399 (94%; 95% confidence interval [CI], 92-96%) were treated successfully and 24
      (6%; 95% CI 3.7-8.3%) failed short-course treatment. Of the 282 patients who
      delivered vaginally, 279 (99%; 95% CI 98-100%) were cured with short-term
      therapy. Of the 141 who delivered by cesarean, 120 (85%; 95% CI 79-91%) were
      cured (P<.001). Seventeen of the patients with total treatment failure had
      endometritis and responded to continuation of antibiotics. Seven patients had
      more serious complications: wound infection (n=4) and septic thrombophlebitis
      (n=3). All of the serious complications occurred after cesarean delivery, and all
      of the affected patients either were obese or had prolonged labor or prolonged
      rupture of membranes. CONCLUSION: A limited course of antibiotics was sufficient
      for virtually all patients (99%) with chorioamnionitis who had a vaginal
      delivery. However, a subset of patients who delivered by cesarean may have
      benefited from a more extended course of antibiotic therapy. LEVEL OF EVIDENCE:
      III.

PMID- 22617574
TI  - Intra-abdominal irrigation at cesarean delivery: a randomized controlled trial.
AB  - OBJECTIVE: To determine whether avoiding intra-abdominal irrigation at cesarean
      delivery will decrease rates of intraoperative and postoperative gastrointestinal
      disturbance without increasing postoperative morbidity. METHODS: This was a
      randomized controlled trial of patients undergoing cesarean delivery. Patients
      were randomized to irrigation after closure of the hysterotomy compared with no
      irrigation. The cesarean delivery was otherwise performed in the usual fashion.
      The patient was blinded to treatment once assigned. The primary outcome was
      maternal intraoperative nausea. The secondary outcomes were postoperative
      maternal gastrointestinal disturbance and incidence of maternal infectious
      morbidity. RESULTS: Two hundred thirty-six patients were randomized; 126 were
      randomized to no irrigation and 110 were randomized to irrigation. Both were
      similar with respect to age, body mass index, operative time, blood loss, uterine
      incision, tubal ligation, exteriorization of the uterus, packing of bowel, lysis
      of adhesions and bladder flap, and peritoneal or rectus muscle closure.
      Intraoperative nausea was significantly more frequent with irrigation compared
      with no irrigation (51 of 110 [46.4%] compared with 36 of 126 [28.26%]; relative
      risk 1.62, 95% confidence interval 1.15-2.28). We noted no statistically
      significant differences for intraoperative emesis, preoperative chorioamnionitis,
      postoperative nausea, postoperative emesis, postoperative antiemetic
      administration, endometritis, or postoperative febrile morbidity. There was an
      increased trend of postoperative nausea and antiemetic use with irrigation.
      CONCLUSION: Irrigation at cesarean delivery increases intraoperative nausea
      without decreasing postoperative infectious morbidity. CLINICAL TRIAL
      REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01479712. LEVEL OF
      EVIDENCE: I.

PMID- 22617575
TI  - Clinical prediction rules for preterm birth in patients presenting with preterm
      labor.
AB  - OBJECTIVE: To develop prediction rules to identify which women with preterm labor
      are at greatest risk for delivery within 10 days and before 37 weeks of gestation
      using demographic and clinical risk factors alone. METHODS: We analyzed data
      collected for a prospective cohort study of singleton pregnancies at 22-33 6/7
      weeks of gestation with preterm labor. Potential risk factors were included in
      multivariable logistic models for each outcome. Using backwards regression, we
      identified combinations of risk factors that generated the most parsimonious yet
      predictive models. Adjusted odds ratios of covariates in the final models were
      used to estimate weights for each risk factor and were summed to generate a
      predictive score. The score associated with the highest negative predictive value
      was defined as a positive test result for each outcome. Bootstrapping techniques
      internally validated the scoring systems. RESULTS: We include data from 583
      women. The risk of delivery within 10 days was 15.4% (n=90) and before 37 weeks
      of gestation it was 35.0% (n=204). The final model for delivery within 10 days
      included initial cervical dilatation, no prenatal care, and tobacco use (area
      under curve=0.75), and for delivery before 37 weeks of gestation it included
      initial cervical dilatation, obstetric history, and tobacco use (area under the
      curve=0.73). A positive test result was associated with 84% sensitivity, 51%
      specificity, 24% positive predictive value, and 95% negative predictive value in
      predicting delivery within 10 days and 79% sensitivity, 50% specificity, 46%
      positive predictive value, and 82% negative predictive value in predicting
      delivery before 37 weeks of gestation. CONCLUSION: Based on their strong negative
      predictive values, these prediction rules could identify patients who do not
      require intensive monitoring when they present with preterm labor. LEVEL OF
      EVIDENCE: II.

PMID- 22617576
TI  - Effect of magnesium sulfate on fetal heart rate patterns in the second stage of
      labor.
AB  - OBJECTIVE: To estimate the effect of maternal exposure to magnesium sulfate on
      fetal heart rate characteristics during active labor. METHODS: Within a 4-year
      retrospective cohort study of consecutive term deliveries reaching the second
      stage of labor, we compared women exposed to magnesium for severe preeclampsia to
      all women not exposed. Primary outcome was the electronic fetal monitoring
      tracing in the 30 minutes preceding delivery. Secondary outcomes were fetal
      acidemia and nursery disposition. Attributable risk estimates and multivariable
      logistic regression were used to estimate the association between magnesium
      exposure and fetal heart rate characteristics. Unadjusted risk estimates for the
      association between fetal heart rate characteristics and neonatal outcomes were
      generated stratified by group. RESULTS: Of 5,387 women, 248 (4.6%) were exposed
      to magnesium. Magnesium exposure was associated with lower fetal heart rate
      baseline (136.9 +/- 12.3 beats per minute compared with 139.0 +/- 13.5 beats per
      minute; P=.02), increased risk of baseline less than 120 beats per minute
      (adjusted odds ratio [OR] 1.76, 95% confidence interval [CI] 1.21-2.56), and
      increased risk of absent or minimal variability (adjusted OR 2.41, 95% CI 1.78
      3.27). More than 20% increased frequency of ever absent or minimal variability
      was attributable to magnesium (attributable risk 0.21, 95% CI 0.15-0.27). There
      were no significant differences in presence or number of accelerations or
      decelerations; however, magnesium was associated with fewer prolonged
      decelerations (adjusted OR 0.64, 95% CI 0.49-0.84). After excluding women with
      adverse neonatal outcomes, these associations remained. CONCLUSION: Maternal
      exposure to magnesium is associated with lower fetal heart rate baseline within
      the accepted normal range, decreased variability, and fewer prolonged
      decelerations without evidence of adverse effect on neonatal outcome. LEVEL OF
      EVIDENCE: II.

PMID- 22617577
TI  - Placental and uterine pathology in women undergoing peripartum hysterectomy.
AB  - OBJECTIVE: To estimate if peripartum hysterectomies performed for intractable
      uterine atony have pathologic findings consistent with infection more often than
      those hysterectomies performed for other indications. METHODS: This is a
      retrospective cohort study of all consecutive peripartum hysterectomies at our
      institution from 1988 to 2009. Scheduled cesarean hysterectomies were excluded.
      Maternal, fetal, and pathologic data were obtained by medical record review.
      Pathologic evaluation was performed for each specimen per a standardized
      protocol. Patients undergoing hysterectomy for uterine atony were compared with
      those requiring hysterectomy for another indication. Pearson's chi and Student's
      t test were used for analysis. RESULTS: Of 324,654 deliveries during the study
      period, 558 (1.7%) women underwent emergent peripartum hysterectomies; 190 (34%)
      were for intractable uterine atony. Those requiring hysterectomy for uterine
      atony were more likely to be at term (87% compared with 62%), have clinical
      chorioamnionitis (19% compared with 6%), and have longer labors (8 hours compared
      with 2.5 hours). Certain placental pathologic findings were significantly more
      common in the atony group, including chorioamnionitis, umbilical vasculitis,
      chorionic plate vasculitis, and funisitis. Acute endometritis and cervicitis were
      also more common in the atony group. Conversely, abnormal placental implantation
      (37% compared with 8%) and leiomyomas (21% compared with 8%) were significantly
      more common in the group requiring hysterectomy for other indications.
      CONCLUSION: Patients requiring emergent peripartum hysterectomies as a result of
      intractable uterine atony are more likely to have clinical and pathologic
      findings consistent with acute inflammation and infection. LEVEL OF EVIDENCE: II.

PMID- 22617578
TI  - Continuous compared with cyclic oral contraceptives for the treatment of primary
      dysmenorrhea: a randomized controlled trial.
AB  - OBJECTIVE: To estimate whether continuous oral contraceptive pills (OCPs) will
      result in more pain relief in primary dysmenorrhea patients than cyclic OCPs,
      which induce withdrawal bleeding with associated pain and symptoms. METHODS: We
      conducted a double-blind, randomized, controlled trial comparing continuous to a
      cyclic 21-7 OCP regimen (gestodene 0.075 mg and ethinyl estradiol 20 microgram)
      for 6 months in 38 primary dysmenorrhea patients. The primary outcome was the
      difference in subjective perception of pain as measured by the visual analog
      scale over a period of 6 months. RESULTS: Twenty-nine patients completed the
      study. In both groups, pain reduction measured by visual analog scale declined
      over time and was significant at 6 months compared with baseline, with no
      difference between groups. Continuous regimen was superior to cyclic regimen
      after 1 month (mean difference -27.3, 95% confidence interval [CI] -40.5 to 
      14.2; P<.001) and 3 months (mean difference -17.8, 95% CI -33.4 to -2.1; P=.03)
      of treatment. Secondary outcomes noted no difference between groups in terms of
      menstrual distress as measured by the Moos Menstrual Distress Questionnaire.
      After 6 months, there was an increase in weight and a decrease in systolic blood
      pressure in the continuous group compared with the cyclic group. CONCLUSION: Both
      regimens of OCPs are effective in the treatment of primary dysmenorrhea.
      Continuous OCPs outperform cyclic OCPs in the short term, but this difference is
      lost after 6 months. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,
      www.clinicaltrials.gov, NCT00517556. LEVEL OF EVIDENCE: I.

PMID- 22617580
TI  - Adherence to conservative management recommendations for abnormal pap test
      results in adolescents.
AB  - OBJECTIVE: To investigate whether the 2006 American Society for Colposcopy and
      Cervical Pathology guidelines for conservative management of minimally abnormal
      Pap test results (atypical squamous cells of undetermined significance, human
      papillomavirus-positive, and low-grade squamous intraepithelial lesions) and
      moderate dysplasia (cervical intraepithelial neoplasia 2) in adolescents 1)
      resulted in fewer colposcopies and loop electrosurgical excision procedures
      (LEEPs) in adolescents or 2) resulted in unintended treatment changes in older
      age groups. METHODS: We analyzed data from 1,806 women aged 18 years and older
      attending one of six community health centers who were diagnosed with abnormal
      Pap test results between January 1, 2004, and December 31, 2008. We used
      multivariable logistic regression to examine treatment differences in women with
      minimally abnormal Pap test results before and after guideline changes. Variables
      included date of abnormality, site of care, race or ethnicity, language, and
      insurance type. We used Fisher exact tests to examine rates of LEEP in patients
      with moderate dysplasia before and after guideline publication. RESULTS: Among
      206 women aged 18-20 years, rates of colposcopy after a minimally abnormal Pap
      test result decreased from 78% (n=102) to 45% (n=34) after guideline changes
      (P<.001). Colposcopy among women over age 21 (n=1,542) remained unchanged
      (greater than 90%). Multivariable logistic regression indicated that both date of
      abnormality and site of care were associated with colposcopy referral. After
      guideline changes, management of moderate dysplasia with LEEP in women aged 18-23
      decreased from 55% to 18% (P=.04); rates remained stable in women ages 24 and
      older (70% compared with 74%; P=.72). CONCLUSION: Health care providers quickly
      adopted new conservative management guidelines for low-income, minority
      adolescents, which may reduce preterm deliveries in these high-risk populations.
      LEVEL OF EVIDENCE: II.

PMID- 22617579
TI  - Altering hirsutism through ovulation induction in women with polycystic ovary
      syndrome.
AB  - OBJECTIVE: Many women with polycystic ovary syndrome (PCOS) experience
      infertility and hirsutism and often seek treatment for both concurrently. We
      investigated whether women who ovulate in response to treatment with clomiphene
      citrate, metformin, or both would have greater improvement in hirsutism compared
      with those who did not ovulate. METHODS: This is a secondary analysis evaluating
      the change in Ferriman-Gallwey score for the hirsute women (n=505 [80.7%]) from
      the Pregnancy in Polycystic Ovary Syndrome I study. This was a prospective,
      randomized, doubled-blind trial of 626 women with PCOS and infertility recruited
      from 12 university sites. They were treated with clomiphene citrate, metformin,
      or both (combination) for up to six cycles, and hirsutism evaluators were blinded
      to group assignment. RESULTS: There was a significant decrease in the Ferriman
      Gallwey score between baseline and completion of the study in each of the three
      individual groups (clomiphene citrate, P=.024; metformin, P=.005; combination,
      P<.001). There was no significant difference in the degree to which the hirsutism
      score changed when comparing the three groups (P=.44). The change in hirsutism
      was not associated with the duration of treatment or with the presence or absence
      of ovulation. CONCLUSION: In infertile hirsute women with PCOS, treatment with
      clomiphene citrate, metformin, or both for up to six cycles does not alter
      hirsutism. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,
      www.clinicaltrials.gov, NCT00068861. LEVEL OF EVIDENCE: II.

PMID- 22617582
TI  - Prevalence and predictors of exclusive breastfeeding at hospital discharge.
AB  - OBJECTIVE: To estimate the population-based prevalence and predictors of
      exclusive breastfeeding at hospital discharge in singleton and twin term
      newborns. METHODS: We studied all hospital births in the province of Ontario,
      Canada, between April 1, 2009, and March 31, 2010, to perform a retrospective
      cohort study. We included live singleton and twin births, at term (37 0/7 weeks
      of gestation to 41 6/7 weeks of gestation), with information about feeding at
      maternal-newborn discharge. Descriptive statistics were performed and logistic
      regression was used to identify factors related to exclusive breastfeeding.
      RESULTS: Our study population consisted of 92,364 newborns, of whom 56,865
      (61.6%) were exclusively breastfed at discharge. Older, nonsmoking, higher-income
      mothers with no pregnancy complications or reproductive assistance were more
      likely to breastfeed. Mothers of twins were less likely to exclusively breastfeed
      (adjusted odds ratio [OR] 0.30, 95% confidence interval [CI] 0.25-0.36) as were
      women who did not attend prenatal classes (adjusted OR 0.80, 95% CI 0.76-0.83).
      Compared with patients of obstetricians (57%), women cared for by midwives (87%,
      adjusted OR 4.49, 95% CI 4.16-4.85) and family physicians (67%, adjusted OR 1.54,
      95% CI 1.47-1.61) were more likely to exclusively breastfeed. Breastfeeding after
      a planned (50%, adjusted OR 0.56, 95% CI 0.52-0.60) or unplanned (48%, adjusted
      OR 0.48, 95% CI 0.44-0.51) cesarean delivery was less common than after a
      spontaneous vaginal birth (68%). Neonates born at 39, 38, and 37 weeks of
      gestation (compared with 41 weeks of gestation) were increasingly less likely to
      breastfeed (adjusted ORs 0.93, 95% CI 0.89-0.98; 0.84, 95% CI 0.80-0.88; and
      0.71, 95% CI 0.67-0.76). CONCLUSION: This large population-based study found that
      fewer than two thirds of term newborns are exclusively breastfed at hospital
      discharge, substantially lower than previously reported. LEVEL OF EVIDENCE: II.

PMID- 22617581
TI  - Cervical ectopy and the acquisition of human papillomavirus in adolescents and
      young women.
AB  - OBJECTIVE: Higher rates of human papillomavirus (HPV) in adolescents and younger
      women have been attributed to their greater extent of "cervical ectopy," defined
      as columnar and metaplastic epithelia on the ectocervix. Our objective was to
      estimate associations between ectopy and incident HPV in healthy adolescents and
      young women. METHODS: Enrolled between October 2000 and October 2002, this
      prospective cohort included women aged 13-21 years who were sexually active,
      without previous cervical intraepithelial neoplasia, cervical procedures, or
      immunosuppression, with menarche within 6 years before enrollment, and negative
      for HPV DNA at baseline. Every 4 months, extent of ectopy was quantitatively
      measured using colpophotography and computerized planimetry. Cox proportional
      hazards models examined associations between ectopy and incident HPV, defined as
      the first positive HPV result during follow-up. RESULTS: The 138 women attended
      509 total visits. At baseline, mean age was 16.7 years and mean extent of ectopy
      was 25% of the total cervical face. Incident HPV of any type was detected in 42
      (30%) women and was not significantly associated with baseline ectopy (hazard
      ratio 1.09, 95% confidence interval 0.96-1.25; P=.20; ectopy in units of 10%), or
      with ectopy measured 4 months before HPV detection (hazard ratio 1.09, confidence
      interval 0.94-1.26; P=.25). Our sample size had 80% power to detect a hazard
      ratio of 1.9 (with two-tailed alpha=0.05). Results were similarly insignificant
      for HPV subgroupings of incident high-risk, low-risk, alpha9, and alpha3/alpha15
      types, and when adjusted for new sexual partners. CONCLUSION: Extent of cervical
      ectopy was not associated with HPV acquisition in healthy adolescents and young
      women. Biological vulnerabilities may lie in immune function or other
      characteristics of the cervical epithelium. LEVEL OF EVIDENCE: II.

PMID- 22617583
TI  - Universal psychosocial screening and adverse pregnancy outcomes in an academic
      obstetric clinic.
AB  - OBJECTIVE: To test the hypothesis that women screened for psychosocial factors,
      including partner abuse, as recommended by the American College of Obstetricians
      and Gynecologists would have higher neonatal birth weight, longer gestational age
      at delivery, higher Apgar scores, and fewer maternal complications. METHODS: We
      evaluated a universal psychosocial screening intervention using a retrospective
      cohort (n=881 prenatal care patients). Pregnancy outcomes among patients screened
      beginning in 2008 (n=464) were compared with outcomes among women receiving care
      before universal screening was implemented (n=417). Data were obtained from
      medical records between 2007 and 2009. Multivariable logistic regression and
      analysis of covariance were used to estimate the association between screening
      and pregnancy outcomes among singleton births adjusting for confounders (prior
      preterm births, insurance, and mode of delivery). RESULTS: Screened women were
      less likely than women not universally screened to have low birth weight neonates
      (4.5% of screened, 10.3% of unscreened; adjusted odds ratio [OR] 0.41, 95%
      confidence interval [CI] 0.23-0.73), preterm births (9.9% of screened, 14.9% of
      unscreened; adjusted OR 0.62, 95% CI 0.41-0.96), and any maternal complication
      (30.0% of screened, 41.2% of unscreened; adjusted OR 0.67, 95% CI 0.50-0.88).
      Newborn Apgar scores were higher (P=.01) among screened relative to unscreened
      mothers. CONCLUSION: Our results provide evidence that universal screening was
      associated with improved pregnancy outcomes. LEVEL OF EVIDENCE: II.

PMID- 22617584
TI  - Angiogenic and fibrinolytic factors in blood during the first half of pregnancy
      and adverse pregnancy outcomes.
AB  - OBJECTIVE: To estimate whether the imbalance of angiogenic factors (soluble fms
      like tyrosine kinase-1, placental growth factor) and fibrinolytic factors
      (plasminogen activator inhibitor-2 [PAI-2]) might affect placentation in early
      pregnancy. METHODS: We studied the associations of maternal soluble fms-like
      tyrosine kinase-1, placental growth factor, and PAI-2 concentrations in the first
      trimester (before 18 weeks of gestation) and soluble fms-like tyrosine kinase-1
      and placental growth factor concentrations in the second trimester (18-25 weeks
      of gestation) with placental function and adverse pregnancy outcomes. This study
      was embedded in a population-based prospective cohort study. Data were used from
      7,519 women. Biomarker concentrations were divided into deciles and evaluated in
      multivariable linear and logistic regression models. RESULTS: First-trimester
      high soluble fms-like tyrosine kinase-1 was associated with a 5.2% lower uterine
      artery index in the second-trimester and a 1.6% higher birth weight (55 g,
      confidence interval [CI] 15-95). Neither in the first nor in the second trimester
      were soluble fms-like tyrosine kinase-1 concentrations significantly associated
      with preeclampsia. First-trimester low placental growth factor was associated
      with a 6.1% higher uterine artery index and a 3.4% lower birth weight (-115 g, CI
      -157 to -74). First-trimester low placental growth factor was associated with
      fetal growth restriction (odds ratio [OR] 2.62, CI 1.68-4.08) and preeclampsia
      (OR 2.46, CI 1.49-4.08). First-trimester low PAI-2 was associated with a 1.9%
      higher uterine artery index and a 2.7% lower birth weight (-94 g, CI -136 to 
      51). First-trimester low PAI-2 was associated with a higher risk of fetal growth
      restriction (OR 2.22, CI 1.39-3.55). CONCLUSION: First-half-of-pregnancy
      concentrations of soluble fms-like tyrosine kinase-1, placental growth factor,
      and PAI-2 are associated with uteroplacental vascular resistance, placental
      weight, and birth weight. Moreover, first-trimester placental growth factor and
      PAI-2 are associated with an increased risk of adverse pregnancy outcomes. LEVEL
      OF EVIDENCE: II.

PMID- 22617585
TI  - Laparoscopic compared with open radical hysterectomy in obese women with early
      stage cervical cancer.
AB  - OBJECTIVE: To compare the surgical and oncological outcomes of laparoscopic
      radical hysterectomy and open radical hysterectomy in obese women with early
      stage cervical cancer. METHODS: The medical records of 166 patients with stage
      IA2-IIA2 cervical cancer and a body mass index of at least 30 who underwent
      laparoscopic radical hysterectomy (n=54) or open radical hysterectomy (n=112) at
      the Asan Medical Center between 1998 and 2011 were reviewed. RESULTS: None of the
      patients in the laparoscopic radical hysterectomy group required conversion to
      laparotomy. The resection margin was negative in 98.1% of the laparoscopic
      radical hysterectomy group and 98.2% of the open radical hysterectomy group
      (P=.976). No difference between the two groups was observed in terms of operating
      time, perioperative hemoglobin level change, transfusion requirement, or the
      number of retrieved lymph nodes. Compared with open radical hysterectomy,
      laparoscopic radical hysterectomy was associated with a significant reduction in
      the following: interval to return of bowel movements (2 days compared with 2.7
      days, P<.001); duration of postoperative hospital stay (9.3 days compared with 21
      days, P<.001), postoperative complications (5.6% compared with 17.9%, P=.032),
      and estimated blood loss (494 mL compared with 620 mL, P=.009). After a median
      follow-up period of 44 months, the 5-year disease-free survival rate was 88% for
      the laparoscopic radical hysterectomy group and 85% for the open radical
      hysterectomy group (P=.682). The 5-year overall survival rate was 97% for the
      laparoscopic radical hysterectomy group and 90% for the open radical hysterectomy
      group (P=.220). CONCLUSION: Laparoscopic radical hysterectomy was a preferred
      alternative to open radical hysterectomy in the present cohort of obese women
      with early-stage cervical cancer because it is associated with a more favorable
      surgical outcome without compromising survival outcomes. LEVEL OF EVIDENCE: II.

PMID- 22617586
TI  - Prognostic value of lymph node ratio and clinicopathologic parameters in patients
      diagnosed with stage IIIC endometrial cancer.
AB  - OBJECTIVE: To estimate the prognostic significance of lymph node ratio with
      respect to clinicopathologic characteristics in stage IIIC endometrial cancer
      patients. METHODS: Using data from medical records and surgery notes, we
      identified all consecutive patients with stage IIIC endometrial cancer who
      received primary surgical treatment between 1993 and 2008. Lymph node ratio is
      the number of metastatic lymph nodes to the total number of removed lymph nodes.
      Survival analyses were performed using Kaplan-Meier and Cox proportional hazard
      methods. RESULTS: Two hundred sixteen patients with stage IIIC endometrial cancer
      were included in this multicenter study. Age, number of metastatic lymph nodes,
      lymph node ratio, grossly suspicious lymph nodes, histologic subtype, and
      cervical metastasis were associated with progression-free survival and overall
      survival, respectively. Patients with lymph node ratios 10% or less, more than 10
      50%, and more than 50% had 5-year overall survival rates of 79.0%, 60.6%, and
      35.8%, respectively (P<.001). In multivariable analysis, only lymph node ratio
      was associated with both progression-free survival and overall survival,
      respectively. Total number of removed lymph nodes and number of metastatic lymph
      nodes did not correlate with overall survival in the group with grossly
      suspicious lymph nodes, whereas lymph node ratio did. In the subgroup of 123
      (56.9%) patients who had pelvic and aortic lymphadenectomies with a minimum of 10
      lymph nodes removed, age and lymph node ratio were still associated with
      progression-free survival and overall survival, whereas total lymph nodes removed
      was not. CONCLUSION: Stratification based on lymph node ratio is useful when
      comprehensive lymphadenectomy is routinely performed and likely reflects
      metastatic nodal tumor burden. These data provide another prognostic variable in
      the heterogenic group of women with stage IIIC endometrial cancer. LEVEL OF
      EVIDENCE: II.

PMID- 22617587
TI  - Vascular pedicle lengths after hysterectomy: toward future human uterus
      transplantation.
AB  - OBJECTIVE: To estimate uterine vessel lengths and diameters recovered at radical
      hysterectomy to assess prospects for direct vascular anastomosis bilaterally to
      the external iliacs in uterus transplantation, and thereby the feasibility of
      live uterus donation as a future treatment of absolute uterine factor
      infertility. METHODS: Patients (n=19; study group) undergoing radical
      hysterectomy for gynecologic malignancy participated. Preoperative magnetic
      resonance imaging (MRI) was performed in four patients to evaluate the usefulness
      in estimation of vessel lengths. At hysterectomy, the uterine arteries and veins
      were dissected separately from the anterior divisions of the internal iliacs to
      their attachments to the uterine cervix. The lengths of the free vascular
      pedicles were measured bilaterally and the distal vessel diameters were recorded.
      The inter-external iliac artery distance, corresponding to distance between
      proposed bilateral anastomosis sites, was measured. Perioperative and
      postoperative outcomes were compared with 76 patients (control group) undergoing
      standard radical hysterectomy without particular uterine vessel dissection.
      RESULTS: The MRI showed uterine artery lengths of 55-100 mm. The duration of
      surgery was slightly longer in the study group (median 297 minutes) compared with
      the control group (262 minutes), but with no differences in perioperative and
      postoperative morbidity. The lengths (median) of the free portions of the left
      uterine artery and vein were 68 mm and 55 mm, and the right uterine artery and
      vein were 65 mm and 50 mm, respectively. The inter-external iliac artery distance
      (median) was 90 mm. CONCLUSION: This study demonstrates that long vascular
      pedicles can be obtained after selective dissections of the uterine arteries and
      veins without compromising postoperative recovery in a live uterine donor
      situation. LEVEL OF EVIDENCE: II.

PMID- 22617588
TI  - Excessive early gestational weight gain and risk of gestational diabetes mellitus
      in nulliparous women.
AB  - OBJECTIVE: To estimate whether there is an association between excessive early
      gestational weight gain and the development of gestational diabetes mellitus
      (GDM) and excessive fetal growth. METHODS: This is a secondary analysis of a
      randomized controlled trial of vitamins C and E in nulliparous low-risk women.
      Maternal weight gain from prepregnancy (self-reported) to 15-18 weeks of
      gestation was measured, and expected gestational weight gain was determined using
      the Institute of Medicine 2009 guidelines for each prepregnancy body mass index
      category. Excessive early gestational weight gain was defined as gestational
      weight gain greater than the upper range of the Institute of Medicine guidelines.
      Rates of GDM, birth weight greater than 4,000 g, and large for gestational age
      (LGA, birth weight 90 percentile or higher) were calculated and compared between
      women with excessive early gestational weight gain and early nonexcessive
      gestational weight gain (within or below Institute of Medicine guidelines).
      RESULTS: A total of 7,985 women were studied. Excessive early gestational weight
      gain occurred in 47.5% of women. Ninety-three percent of women with excessive
      early gestational weight gain had total gestational weight gain greater than
      Institute of Medicine guidelines. In contrast, only 55% of women with
      nonexcessive early gestational weight gain had total gestational weight gain
      greater than Institute of Medicine guidelines (P<.001). Rates of GDM, LGA, and
      birth weight greater than 4,000 g were higher in women with excessive early
      gestational weight gain. CONCLUSION: In our population, excessive early
      gestational weight gain occurred in 93% of women who had total gestational weight
      gain greater than the Institute of Medicine guidelines. In low-risk nulliparous
      women, excessive early gestational weight gain is associated with the development
      of GDM and excessive fetal growth. LEVEL OF EVIDENCE: II.

PMID- 22617590
TI  - Maternal tryptophan and kynurenine pathway metabolites and risk of preeclampsia.
AB  - OBJECTIVE: To estimate the association of maternal plasma concentrations of
      tryptophan and six kynurenine pathway metabolites with the risk of preeclampsia.
      METHODS: The study was based on a subsample of 2,936 pregnant women who delivered
      singleton neonates in the Norwegian Mother and Child Cohort Study in 2002-2003.
      Maternal blood plasma was obtained at approximately gestational week 18 and was
      measured for tryptophan, kynurenine, kynurenic acid, anthranilic acid, 3
      hydroxykynurenine, xanthurenic acid, and 3-hydroxyanthranilic acid. RESULTS: Of
      the 2,936 pregnant women included in this study, 116 (4.0%, 95% confidence
      interval [CI] 3.2-4.7) had preeclampsia subsequently diagnosed. The prevalence of
      preeclampsia was significantly higher among women with plasma kynurenic acid
      concentrations greater than the 95th percentile than among those with
      concentrations in the 25th-75th percentile (11.0% compared with 3.3%, P<.001;
      adjusted odds ratio 3.6, 95% CI 1.9-6.8). This association was significantly
      stronger in women with prepregnancy body mass index of 25 or more (P for
      interaction=.03; 20.4% compared with 4.2%; P<.001). No statistically significant
      associations of preeclampsia with other tryptophan metabolites were found.
      CONCLUSION: Elevated maternal plasma kynurenic acid concentrations in early
      pregnancy are associated with a substantial increased risk of preeclampsia in
      obese women. LEVEL OF EVIDENCE: II.

PMID- 22617591
TI  - Placental weight for gestational age and adverse perinatal outcomes.
AB  - OBJECTIVE: The fetoplacental ratio has been used conventionally to study the
      contribution of the placenta to fetal growth restriction. However, this measure
      is problematic because a normal fetoplacental ratio can reflect birth weight and
      placental weight that are both normal, both low, or both high. The objective of
      this study was to examine the independent association between placental weight
      for gestational age and perinatal mortality or serious neonatal morbidity.
      METHODS: A sex- and gestational age-specific placental weight z score was
      calculated for a cohort of 87,600 singleton births at the Royal Victoria Hospital
      in Montreal, Canada, 1978-2007. The relationship between placental weight z score
      and adverse perinatal outcomes (stillbirth, neonatal death, 5-minute Apgar score
      lower than 7, seizures, or respiratory morbidity) was examined using logistic
      regression. Multivariable models examined whether the relationship was
      independent of birth weight and other pregnancy risk factors. RESULTS: : After
      controlling for birth weight, fetuses with a low placental weight z score were at
      significantly increased risk of stillbirth (odds ratio [OR] 2.0, 95% confidence
      interval [CI] 1.4-2.6, percent population attributable risk 17.8%). In contrast,
      adverse neonatal outcomes were significantly more likely among those with high
      placental weight z scores (OR 1.4, 95% CI 1.2-1.7, percent population
      attributable risk 5% for any serious neonatal morbidity). Similar trends were
      observed after further adjusting for pregnancy risk factors. CONCLUSION:
      Placental weight for gestational age is an independent risk factor for adverse
      perinatal outcomes, above and beyond the known association with birth weight. The
      mechanisms behind the opposing effects of placental weight z score on risk of
      stillbirth compared with adverse neonatal outcomes require further elucidation.
      LEVEL OF EVIDENCE: III.

PMID- 22617589
TI  - First-trimester prediction of preeclampsia in nulliparous women at low risk.
AB  - OBJECTIVE: To identify clinical characteristics and biochemical markers in first
      trimester samples that would possibly predict the subsequent development of
      preeclampsia. METHODS: We conducted a multicenter observational study in 2,434
      nulliparous women at low risk to identify biomarkers that possibly predict
      preeclampsia. Clinical history, complete blood count, and biochemical markers
      were assessed in the first trimester. The trophoblast and angiogenesis markers
      ADAM-12, pregnancy-associated plasma protein-A, placental protein 13, placental
      growth factor, soluble fms-like tyrosine kinase-1, and endoglin were measured in
      a case-control subset of 174 women with preeclampsia and 509 women in the control
      group. RESULTS: Univariable analysis revealed maternal age, race, marital status,
      years of education, source of medical payment, prenatal caregiver, body mass
      index (BMI, calculated as weight (kg)/[height (m)]), and systolic blood pressure
      at enrollment were significantly associated with preeclampsia. Mean platelet
      volume was greater at enrollment in women who later had development of
      preeclampsia (median 9.4 compared with 9.0 femtoliter (fl); P=.02). First
      trimester concentrations (multiples of the median) of ADAM-12 (1.14 compared with
      1.04; P=.003), pregnancy-associated plasma protein-A (0.94 compared with 0.98;
      P=.04), and placental growth factor (0.83 compared with 1.04; P<.001) were
      significantly different in women who had development of preeclampsia compared
      with women in the control group. The optimal multivariable model included African
      American race, systolic blood pressure, BMI, education level, ADAM-12, pregnancy
      associated plasma protein-A, and placental growth factor, and yielded an area
      under the curve of 0.73 (95% confidence interval 0.69-0.77) and a sensitivity of
      46.1% (95% confidence interval 38.3-54.0) for 80% specificity. CONCLUSION: A
      multivariable analysis of clinical data and biochemical markers in the first
      trimester did not identify a model that had clinical utility for predicting
      preeclampsia in a nulliparous population at low risk. LEVEL OF EVIDENCE: II.

PMID- 22617593
TI  - Gynecologic surgery in the geriatric patient.

PMID- 22617594
TI  - Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing.

PMID- 22617596
TI  - The comparative safety of legal induced abortion and childbirth in the United
      States.

PMID- 22617597
TI  - The comparative safety of legal induced abortion and childbirth in the United
      States.

PMID- 22617599
TI  - Abortion, pregnancy, and public health.

PMID- 22617600
TI  - Abortion, pregnancy, and public health.

PMID- 22617602
TI  - Unverifiable and erroneous publications reported by obstetrics and gynecology
      residency applicants.

PMID- 22617603
TI  - Unverifiable and erroneous publications reported by obstetrics and gynecology
      residency applicants.

PMID- 22617605
TI  - Homicide and suicide during the perinatal period: findings from the National
      Violent Death Reporting System.

PMID- 22617607
TI  - Optimum timing for planned delivery of uncomplicated monochorionic and
      dichorionic twin pregnancies.

PMID- 22617615
TI  - ACOG practice bulletin no. 127: Management of preterm labor.
AB  - Preterm birth is the leading cause of neonatal mortality and the most common
      reason for antenatal hospitalization(1-4). In the United States, approximately
      12% of all live births occur before term, and preterm labor preceded
      approximately 50% of these preterm births (5, 6). Although the causes of preterm
      labor are not well understood, the burden of preterm births is clear-preterm
      births account for approximately 70% of neonatal deaths and 36% of infant deaths
      as well as 25-50% of cases of long-term neurologic impairment in children (7-9).
      A 2006 report from the Institute of Medicine estimated the annual cost of preterm
      birth in the United States to be $26.2 billion or more than$51,000 per premature
      infant (10). However, identifying women who will give birth preterm is an inexact
      process.The purpose of this document is to present the various methods proposed
      to manage preterm labor and to review the evidence for the roles of these methods
      in clinical practice. Identification and management of risk factors for preterm
      labor are not addressed in this document.

PMID- 22617616
TI  - ACOG committee opinion no. 527: Personalized genomic testing for disease risk.
AB  - Advances in genetic technologies have led to the identification of hundreds of
      single that are associated with a variety of complex diseases, including cancer,
      diabetes, cardiovascular disease, and Alzheimer disease. Although personalized
      genomic tests that provide information regarding the risk of development of
      multiple diseases may be important tools in the near future, their use is not
      recommended outside of a clinical trial until these tests are validated as
      clinically useful in appropriately designed prospective studies.Testing for
      single-gene disorders should be approached in accordance with accepted guidelines
      that address the evaluation and management of these specific diseases.

PMID- 22617617
TI  - ACOG committee opinion no. 528: Adoption.
AB  - Obstetrician-gynecologists may find themselves at the center of adoption issues
      because of their expertise in the assessment and management of infertility,
      pregnancy, and childbirth. The lack of clarity about both ethical issues and
      legal consequences may create challenges for physicians. Therefore, the Committee
      on Ethics of the American College of Obstetricians and Gynecologists discusses
      ethical issues, proposes safeguards,and makes recommendations regarding the role
      of the physician in adoption.

PMID- 22617618
TI  - ACOG technology assessment no. 8: Sonohysterography.
AB  - The primary goal of sonohysterography is to visualize the endometrial cavity in
      more detail than is possible with routine transvaginal ultrasonography. The
      procedure consists of the transcervical injection of sterile fluid under real
      time ultrasound imaging. The indications for sonohysterography include, but are
      not limited to, the evaluation of abnormal uterine bleeding; uterine cavity,
      especially with regard to uterine leiomyomas,polyps, and synechiae; abnormalities
      detected on transvaginal ultrasonography,including focal or diffuse endometrial
      or intracavitary abnormalities;congenital abnormalities of the uterus;
      infertility; and recurrent pregnancy loss. The procedure should not be performed
      in a woman who is pregnant or who could be pregnant or who has an existing pelvic
      infection or unexplained pelvic tenderness. Physicians who perform or supervise
      diagnostic sonohysterography should be skilled in vaginal ultrasonography and
      transcervical placement of catheters; should have training, experience, and
      demonstrated competence in gynecologic ultrasonography and sonohysterography; and
      should keep careful records. Portions of this document were developed jointly
      with the American College of Radiology, the American Institute of Ultrasound in
      Medicine, and the Society of Radiologists in Ultrasound.

PMID- 22617620
TI  - Multimodality imaging and the emerging role of cardiac magnetic resonance in
      autoimmune myocarditis.
AB  - Autoimmune responses and inflammation are involved in the excess cardiovascular
      risk observed in patients with systemic inflammatory diseases. Autoimmune
      myocarditis is a presentation of an inflammatory reaction of the heart during the
      course of autoimmune disorders, with most cases seen in systemic lupus
      erythematosus. Early diagnosis is of great significance because of the likelihood
      of progression to severe and potentially fatal complications such as arrhythmias,
      heart block, and heart failure. The clinical presentation of the disease is
      silent leading to delayed diagnosis when dilated cardiomyopathy or heart failure
      has already advanced. Therefore, a major issue is whether the diagnosis of
      myocarditis will continue to require invasive procedures such as endomyocardial
      biopsy or can be achieved with non-invasive methods. There is increasing evidence
      that noninvasive cardiac imaging, including tissue Doppler echocardiography and
      cardiac magnetic resonance (CMR), is able to detect subclinical cases and aid in
      the initiation of specific treatment when it is more likely to be effective. CMR
      in particular, has emerged as an important technique in the evaluation of
      myocarditis using three types of images: T2-weighted (T2-W), early T1-weighted
      (EGE) images taken after 1 min, and delayed enhanced images (LGE) taken 15 min
      after the injection of contrast agent. If 2/3 of the imaging sequences are
      positive, myocardial inflammation can be predicted or ruled out with a diagnostic
      accuracy of 78%. As our understanding of disease mechanisms improves,
      multimodality imaging may aid in the development of new diagnostic and
      therapeutic strategies for this potentially devastating complication of systemic
      inflammation, but further studies are needed to formally evaluate this.

PMID- 22617621
TI  - Persistent currents in a graphene ring with armchair edges.
AB  - A  graphene nanoribbon with armchair edges is known to have no edge state.
      However, if the nanoribbon is in the quantum spin Hall state, then there must  be
      helical edge states. By folding a graphene ribbon into a ring and threading it by
      a magnetic flux, we study the persistent charge and spin currents in the tight
      binding limit. It is found that, for a broad ribbon, the edge spin current
      approaches a finite value independent of the radius of the ring. For a narrow
      ribbon, inter-edge coupling between the edge states could open the Dirac gap and
      reduce the overall persistent currents. Furthermore, by enhancing the Rashba
      coupling, we find that the persistent spin current gradually reduces to zero at a
      critical value beyond which the graphene is no longer a quantum spin Hall
      insulator.

PMID- 22617619
TI  - Cultural and religious considerations in pediatric palliative care.
AB  - OBJECTIVE: A growing multicultural society presents healthcare providers with a
      difficult task of providing appropriate care for individuals who have different
      life experiences, beliefs, value systems, religions, languages, and notions of
      healthcare. This is especially vital when end-of-life care is needed during
      childhood. There is a dearth of literature addressing cultural considerations in
      the pediatric palliative care field. As members of a specific culture often do
      not ascribe to the same religious traditions, the purpose of this article was to
      explore and review how culture and religion informs and shapes pediatric
      palliative care. METHOD: Comprehensive literature searches were completed through
      an online search of nine databases for articles published between 1980 and 2011:
      PsychINFO, MEDLINE(r), Journal of Citation Reports-Science Edition, Embase,
      Scopus, CINAHL(r), Social Sciences Citation Index (SSCI), EBSCO, and Ovid. Key
      terms included: culture, transcultural, spiritual, international, ethnic, customs
      or religion AND end-of-life, palliative care, death, dying, cancer, or hospice,
      and children, pediatrics, or pediatric oncology. Reference lists in the retrieved
      articles were examined for additional studies that fit the inclusion criteria,
      and relevant articles were included for review. In addition, web-based searches
      of specific journals were conducted. These included, but were not limited to:
      Qualitative Health Research, Psycho-Oncology, Journal of Psychosocial Oncology,
      Journal of Pediatric Psychology, Journal of Pediatric Health Care, Journal of
      Pediatric Oncology Nursing, Omega, Social Work in Health Care, and Journal of
      Palliative Medicine. RESULTS: Thirty-seven articles met eligibility criteria.
      From these, seven distinct themes emerged that have implications for pediatric
      palliative care. These include the role of culture in decision-making, faith and
      the involvement of clergy, communication (spoken and unspoken language),
      communicating to children about death (truth telling), the meaning of pain and
      suffering, the meaning of death and dying, and location of end-of-life care.
      SIGNIFICANCE OF RESULTS: The review of the literature provides insight into the
      influence of religion and how culture informs lifestyle and shapes the
      experiences of illness, pain, and end-of-life care. Recommendations for providing
      culturally sensitive end-of-life care are offered through the framework outlined
      in the Initiative for Pediatric Palliative Care Quality Improvement Project of
      2002. Cultural traditions are dynamic, never static, and cannot be generalized to
      all families. Guidelines to aid in approaches to palliative care are provided,
      and providers are encouraged to define these important differences for each
      family under their care.

PMID- 22617622
TI  - Improvement of antioxidant activity of peptides with molecular weights ranging
      from 1 to 10 kDa by PEF technology.
AB  - Egg white protein powder was hydrolyzed with Alcalase to produce antioxidant
      peptides. Then, the peptides were fractionated with ultrafiltration membranes.
      The peptides (1-10 kDa) were further treated by pulsed electric field (PEF) to
      investigate its effect on the antioxidant activity of the peptides. Antioxidant
      activity was evaluated using a 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical
      inhibition assay. The results indicated that optimal electric field intensity and
      standing times of PEF can enhance the antioxidant activity of the peptides.
      Therefore, a Box-Behnken design (BBD) with three independent variables including
      concentration, electric field intensity and pulse frequency was used to establish
      the regression equation of second-order response surface. The optimal conditions
      were as follows: concentration 8 mg/ml, electric field intensity 10 kV/cm and
      pulse frequency 2400 Hz. Under these conditions, the peptides antioxidant
      activity was 62.64% +/- 0.98%. The present study demonstrated that the
      antioxidant activity of peptides (1-10 kDa) could be improved using PEF.

PMID- 22617623
TI  - Cellulose nanofibrils prepared from softwood cellulose by TEMPO/NaClO/NaClO2
      systems in water at pH 4.8 or 6.8.
AB  - Catalytic oxidation of softwood cellulose using NaClO and either 2,2,6,6
      tetramethylpiperidine-1-oxyl (4-H-TEMPO) or 4-acetamido-TEMPO (4-AcNH-TEMPO) was
      applied with NaClO(2) used as a primary oxidant in an aqueous buffer at pH 4.8 or
      6.8. When the 4-AcNH-TEMPO-mediated oxidation was applied to softwood cellulose
      in water at pH 4.8 and 40  degrees C, the carboxylate content rose to ~1.3 mmol/g
      after reaction for 48 h and the DP(v) value was more than 1100. This 4-AcNH-TEMPO
      oxidized softwood cellulose was mostly converted to individual nanofibrils by
      mechanical disintegration in water, with uniform widths of 3-4 nm and lengths
      greater than 1 MUm.

PMID- 22617624
TI  - Human internal mammary artery (IMA) transplantation and stenting: a human model
      to study the development of in-stent restenosis.
AB  - Preclinical in vivo research models to investigate pathobiological and
      pathophysiological processes in the development of intimal hyperplasia after
      vessel stenting are crucial for translational approaches (1,2). The commonly used
      animal models include mice, rats, rabbits, and pigs (3-5). However, the
      translation of these models into clinical settings remains difficult, since those
      biological processes are already studied in animal vessels but never performed
      before in human research models (6,7). In this video we demonstrate a new
      humanized model to overcome this translational gap. The shown procedure is
      reproducible, easy, and fast to perform and is suitable to study the development
      of intimal hyperplasia and the applicability of diverse stents. This video shows
      how to perform the stent technique in human vessels followed by transplantation
      into immunodeficient rats, and identifies the origin of proliferating cells as
      human.

PMID- 22617626
TI  - Imaging-guided curative surgical resection of pancreatic cancer in a xenograft
      mouse model.
AB  - Pancreatic cancer is the fourth leading cause of cancer related deaths in North
      America. The poor survival statistics are due to the fact that there are no
      reliable tests for early diagnosis and no effective therapies once metastasis has
      occurred. Surgical resection is the only curative treatment for pancreatic
      cancer; however, only less than 15% of the patients are eligible for surgery at
      diagnosis. New therapies are urgently needed for this malignant disease. And
      combinational therapy including surgery, chemotherapy and molecular targeted
      therapy may further improve the efficacy of individual therapies. However, a
      reliable mouse model which mimics the human disease and can be used for testing
      the surgical treatment and surgery-based combinational therapy is not available.
      In this study, we have established a mouse model for curative surgical resection
      of pancreatic cancer. Human pancreatic cancer cells were used to create
      orthotopic xenografts in nude mice, distal pancreatectomy was performed using
      imaging-guided technology to remove the pancreatic tumors, and sham surgery was
      performed in the control group. All mice survived the operation and no
      complication was observed. Surgical resection at early stage improved the
      survival rate and quality of life of the mice compared with the sham surgery and
      surgical resection at the late stage. If combined with other therapies such as
      chemotherapy and molecular targeted therapy, it could further improve the outcome
      of pancreatic cancer. This mouse model is a useful tool to study the surgical
      therapy and the tumor recurrence of pancreatic cancer, and could potentially
      impact the therapeutic choices for this deadly disease.

PMID- 22617627
TI  - Supra-physiological folic acid concentrations induce aberrant DNA methylation in
      normal human cells in vitro.
AB  - The micronutrients folate and selenium may modulate DNA methylation patterns by
      affecting intracellular levels of the methyl donor S-adenosylmethionine (SAM)
      and/or the product of methylation reactions S-adenosylhomocysteine (SAH). WI-38
      fibroblasts and FHC colon epithelial cells were cultured in the presence of two
      forms of folate or four forms of selenium at physiologically-relevant doses, and
      their effects on LINE-1 methylation, gene-specific CpG island (CGI) methylation
      and intracellular SAM:SAH were determined. At physiologically-relevant doses the
      forms of folate or selenium had no effect on LINE-1 or CGI methylation, nor on
      intracellular SAM:SAH. However the commercial cell culture media used for the
      selenium studies, containing supra-physiological concentrations of folic acid,
      induced LINE-1 hypomethylation, CGI hypermethylation and decreased intracellular
      SAM:SAH in both cell lines. We conclude that the exposure of normal human cells
      to supra-physiological folic acid concentrations present in commercial cell
      culture media perturbs the intracellular SAM:SAH ratio and induces aberrant DNA
      methylation.

PMID- 22617625
TI  - Reduced neural activity of the prefrontal cognitive control circuitry during
      response inhibition to negative words in people with schizophrenia.
AB  - BACKGROUND: Schizophrenia is characterized by deficits in executive control and
      impairments in emotion processing. This study assessed the nature and extent of
      potential alterations in the neural substrates supporting the interaction between
      cognitive control mechanisms and emotion attribution processes in people with
      schizophrenia. METHODS: Functional magnetic resonance imaging was performed
      during a verbal emotional go/no-go task. People with schizophrenia and healthy
      controls responded to word stimuli of a prespecified emotional valence (positive,
      negative or neutral) while inhibiting responses to stimuli of a different
      valence. RESULTS: We enrolled 20 people with schizophrenia and 23 controls in the
      study. Healthy controls activated an extensive dorsal prefrontal-parietal network
      while inhibiting responses to negative words compared to neutral words, but
      showed deactivation of the midcingulate cortex while inhibiting responses to
      positive words compared to neutral words. People with schizophrenia failed to
      activate this network during response inhibition to negative words, whereas
      during response inhibition to positive words they did not deactivate the
      cingulate, but showed increased responsivity in the frontal cortex. LIMITATIONS:
      Sample heterogeneity is characteristic of studies of schizophrenia and may have
      contributed to more variable neural responses in the patient sample despite the
      care taken to control for potentially confounding variables. CONCLUSION: Our
      results showed that schizophrenia is associated with aberrant modulation of
      neural responses during the interaction between cognitive control and emotion
      processing. Failure of the frontal circuitry to regulate goal-directed behaviour
      based on emotion attributions may contribute to deficits in psychosocial
      functioning in daily life.

PMID- 22617628
TI  - Pituitary adenoma pathogenesis:  an update.
AB  - PURPOSE OF REVIEW: To describe the recent efforts to understand the molecular and
      genetic mechanisms involved in the tumorigenesis of pituitary adenomas. RECENT
      FINDINGS: There is rapidly accumulating evidence for the roles of molecular
      abnormalities in pituitary adenoma tumorigenesis, including dysregulation of the
      cell cycle, signal transduction pathways, oncogenes and tumor suppressor genes.
      MicroRNAs have been identified as important participants in gene regulation and
      may have a role in therapy. Stem cells have also provided novel concepts for
      tumorigenesis and potentially treatment. SUMMARY: Pituitary adenomas are
      relatively common neoplasms, whose pathogenesis is still poorly understood.
      Although considered by many as benign monoclonal proliferations, their clinical
      spectrum is diverse including hormone hypersecretion, and various degrees of
      invasiveness, suggesting multiple steps and mechanisms. This review summarizes
      recent development in the molecular tumorigenesis of pituitary adenomas
      emphasizing the dysregulation of the cell cycle components, tumor suppressor
      genes, oncogenes, stem cells and microRNAs.

PMID- 22617629
TI  - Chlorophyll index, photochemical reflectance index and chlorophyll fluorescence
      measurements of rice leaves supplied with different N levels.
AB  - Rapid and non-destructive diagnosis of plant N status is highly required in order
      to optimise N fertilizer management and use-efficiency. Additionally to handheld
      devices for measurements of chlorophyll indices (e.g., SPAD meter) parameters of
      canopy reflectance via remote sensing approaches are intensively investigated and
      the photochemical reflectance index (PRI) appears to be a reliable indicator for
      changes of the epoxidation state of xanthophyll cycle pigments. In order to
      assess the suitability of a handheld PRI as an additional tool for N diagnosis,
      rice plants were grown in a nutrient solution experiment with seven N-supply
      levels (0.18-5.71 mM) and CI (SPAD) and PRI values and chlorophyll fluorescence
      parameters measured 20 and 28 days after onset of treatments. N-supply had
      effects on both CI (SPAD) and PRI values with a more reliable differentiation
      between levels. Maximum quantum yield of PSII (F(v)/F(m)), actual efficiency of
      PSII photochemistry (F(PSII)) and regulated non-photochemical quenching (F(NPQ))
      did not differ significantly between N levels. Non-photochemical quenching (NPQ)
      and fast- relaxing NPQ (NPQ(F)) were significantly affected by N-supply. NPQ and
      NPQ(F), but not the slow-relaxing component (NPQ(S)), were correlated with CI
      (SPAD) and PRI values. This finding which has not been reported for N-supply
      effects so far is indirect evidence that low N-supply induced xanthophyll cycle
      activity and that PRI values are able to indicate this at least in plants subject
      to severe N deficiency.

PMID- 22617630
TI  - Enantioselective catalysis with a chiral, phosphane-containing PMO material.
AB  - A novel bistriethoxysilyl-BINAP monomer was prepared and co-condensed with a
      biphenylene-bridged siloxane precursor in the presence of surfactant templates to
      give periodic mesoporous organosilicas (PMOs) functionalized with BINAP.
      Complexation of ruthenium followed by asymmetric catalytic hydrogenation and
      asymmetric transfer hydrogenation were carried out, and demonstrated that high
      levels of activity and selectivity are achievable with the chiral material.

PMID- 22617631
TI  - Reduction of fear of movement-related pain and pain-related anxiety: An
      associative learning approach using a voluntary movement paradigm.
AB  - The fear-avoidance model advances fear of pain as a key factor in the origins of
      chronic pain disability. Initial evidence in those with chronic back pain reveals
      that exposure therapy reduces fear levels, disability, and pain. Despite the
      success of exposure in the clinic, fundamental research about its underlying
      mechanisms lags behind. Using a conditioning paradigm with movements as
      conditioned stimuli (CS) and a painful shock as unconditioned stimuli (US), we
      investigated the extinction of experimental fear of movement-related pain and
      pain-related anxiety (respectively induced by predictable and unpredictable
      pain). Dependent measures were self-reported fear and eyeblink startle. During
      acquisition, all groups received both predictable and unpredictable training. In
      the predictable context, one movement (CS+) was consistently followed by the
      shock-US, but another movement was not (CS-). In the unpredictable context,
      joystick movements never signaled the shock-US; shock-US were delivered during
      the intertrial interval (ITI). During extinction, the extinction group continued
      training in the predictable context but the CS+ movement was no longer
      reinforced; the context exposure group continued training in the unpredictable
      context but ITI shock-US were omitted. The control group continued training after
      the acquisition reinforcement scheme. Results revealed that fear ratings for the
      CS+ were extinguished in the extinction group but not in the control group.
      Interestingly, omitting the ITI shocks not only reduced ITI startle responses in
      the context exposure group compared with the control group, but also reduced the
      fear ratings and startle responses elicited by the unpredictable CS. The clinical
      implications of these findings are discussed.

PMID- 22617632
TI  - Cognitive Behavioral Therapy increases pain-evoked activation of the prefrontal
      cortex in patients with fibromyalgia.
AB  - Interventions based on Cognitive Behavioral Therapy (CBT) are widely used to
      treat chronic pain, but the brain mechanisms responsible for these treatment
      effects are poorly understood. The aim of this study was to validate the
      relevance of the cortical control theory in response to an exposure-based form of
      CBT, Acceptance and Commitment Therapy, in patients with chronic pain. Forty
      three female patients diagnosed with fibromyalgia syndrome were enrolled in a
      randomized, 12-week, waiting-list controlled clinical trial (CBT n=25; controls
      n=18). CBT was administered in groups of six patients during 12 weekly sessions.
      Functional magnetic resonance imaging (fMRI) during pressure-evoked pain was
      assessed before and after treatment or the 12-week period. Self-report
      questionnaires of depression and anxiety were administered pre- and posttreatment
      as well as 3 months following end of treatment. Patients treated with CBT
      reported larger improvement of fibromyalgia on the Patient Global Impression of
      Change measure, and improved depression and anxiety symptoms, compared to the
      waiting-list controls. However, there were no effects on clinical pain or pain
      sensitivity measures. An analysis of fMRI scans revealed that CBT led to
      increased activations in the ventrolateral prefrontal/lateral orbitofrontal
      cortex; regions associated with executive cognitive control. We suggest that CBT
      changes the brain's processing of pain through an altered cerebral loop between
      pain signals, emotions, and cognitions; leading to increased access to executive
      regions for reappraisal of pain. Our data thereby support our hypothesis about
      the activation of a cortical control mechanism in response to CBT treatment in
      chronic pain.

PMID- 22617633
TI  - Survey of the prevalence of immunization non-compliance due to needle fears in
      children and adults.
AB  - Needle fears are a documented barrier to immunization in children and adults.
      There is a paucity of data, however, regarding the prevalence of needle fears and
      their impact on immunization compliance. In this cross-sectional survey, a
      convenience sample of parents (n=883) and children (n=1024) attending a public
      museum in Toronto, Canada answered questions about needle fears and non
      compliance with immunization due to needle fear. Altogether, 24% of parents and
      63% of children reported a fear of needles. Needle fear was the primary reason
      for immunization non-compliance for 7% and 8% of parents and children,
      respectively. Interventions aimed at improving education about, and access to,
      analgesic interventions during immunization injections performed in childhood are
      recommended in order to prevent the development of needle fears and vaccine non
      compliance.

PMID- 22617634
TI  - Orexin-A excites pyramidal neurons in layer 2/3 of the rat prefrontal cortex.
AB  - The arousal peptides, orexins, play an important role in regulating the function
      of the prefrontal cortex (PFC). Although orexins have been shown to increase the
      excitability of deep-layer neurons in the medial prefrontal cortex (mPFC), little
      is known about their effect on layer 2/3, the main intracortical processing
      layer. In this study, we investigated the effect of orexin-A on pyramidal neurons
      in layer 2/3 of the mPFC using whole-cell recordings in rat brain slices. We
      observed that orexin-A reversibly depolarized layer 2/3 pyramidal neurons through
      a postsynaptic action. This depolarization was concentration-dependent and
      mediated via orexin receptor 1. In voltage-clamp recordings, the orexin-A-induced
      current was reduced by the replacement of internal K(+) with Cs(+), removal of
      external Na(+), or an application of flufenamic acid (an inhibitor of
      nonselective cation channels). A blocker of Na(+)/Ca(2+) exchangers (SN-6) did
      not influence the excitatory effect of orexin-A. Moreover, the current induced by
      orexin-A reversed near E(k) when the external solution contained low levels of
      Na(+). When recording with Cs(+)-containing pipettes in normal external solution,
      the reversal potential of the current was approximately -25 mV. These data
      suggest an involvement of both K(+) channels and nonselective cation channels in
      the effect of orexin-A. The direct excitatory action of orexin-A on layer 2/3
      mPFC neurons may contribute to the modulation of PFC activity, and play a role in
      cognitive arousal.

PMID- 22617635
TI  - Meloxicam ameliorates motor dysfunction and dopaminergic neurodegeneration by
      maintaining Akt-signaling in a mouse Parkinson's disease model.
AB  - A series of oxicam non-steroidal anti-inflammatory drugs (NSAIDs) have been shown
      to be neuroprotective against 1-methyl-4-phenyl pyridinium in human neuroblastoma
      SH-SY5Y cells via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway
      independent of cyclooxygenase (COX) inhibition. The present study endeavored to
      establish this novel effect of meloxicam (MLX), an oxicam NSAID, in a mouse
      Parkinson's disease (PD) model using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP). Male C57BL/6 mice, which received MPTP (30 mg/kg/day; s.c.) for 5
      consecutive days (chronic model) with 10-day follow-up saline administrations,
      showed significant motor dysfunction in the pole test due to reduced tyrosine
      hydroxylase (TH) protein levels in the brain on day 16 after MPTP/saline
      treatment. Daily coadministrations of MLX (10mg/kg/day; i.p.) and MPTP for the
      first 5 days and follow-up 10 days with MLX administrations alone (MPTP/MLX
      treatment) significantly ameliorated MPTP-induced behavioral abnormalities in
      mice. Concomitant decreases of TH protein levels in the striatum and midbrain of
      MPTP/MLX-treated mice were not only significantly (p<0.01 and p<0.05,
      respectively) ameliorated but phosphorylated Akt (pAkt473) expression in the
      midbrain was also significantly (p<0.01) increased in the midbrain when compared
      with MPTP/saline-treated mice. These results suggest that MLX, an oxicam NSAID,
      attenuated dopaminergic neuronal death in the experimental MPTP-PD model by
      maintenance of the Akt-signaling. Oxicam NSAIDs may serve as potential drugs for
      PD treatment via a novel mechanism of action.

PMID- 22617636
TI  - Discovering Alzheimer's disease and bipolar disorder white matter effects
      building computer aided diagnostic systems on brain diffusion tensor imaging
      features.
AB  - The aim of this study is to look for differential effects in white matter (WM) of
      bipolar disorder (BD) and Alzheimer's disease (AD) patients. We proceed by
      investigating the feasibility of discriminating between BD and AD patients, and
      from healthy controls (HC), using multivariate data analysis based on diffusion
      tensor imaging (DTI) data features. Specifically, support vector machine (SVM)
      classifiers were trained and tested on fractional anisotropy (FA). Voxel sites
      are selected as features for classification if their Pearson's correlation
      between FA values at voxel site across subjects and the indicative variable
      specifying the subject class is above the threshold set by a percentile of its
      empirical distribution. To avoid double dipping, selection was performed only on
      training data in a leave one out cross-validation study. Classification results
      show that FA features and a linear SVM classifier achieve perfect accuracy,
      sensitivity and specificity in AD vs. HC, BD vs. HC, and AD vs. BD leave-one-out
      cross-validation studies. The localization of the discriminant voxel sites on a
      probabilistic tractography atlas shows effects on seven major WM tracts in each
      hemisphere and two commissural tracts.

PMID- 22617637
TI  - Neonatal handling and environmental enrichment increase the expression of GAP-43
      in the hippocampus and promote cognitive abilities in prenatally stressed rat
      offspring.
AB  - Neonatal handling and environmental enrichment have been used to aid the
      treatment and recovery of a diverse variety of brain dysfunctions. However, the
      underlying mechanism and the effects on cognitive function following neonatal
      handling and environmental enrichment are still unclear. In this study, we
      investigated GAP-43 protein levels in the hippocampus of prenatally stressed rat
      pups by Western blot on postnatal day (P) 10, P20 and P45. The cognitive ability
      of prenatally stressed rat pups was tested by using the Morris water maze on P45.
      GAP-43 protein levels were upregulated on P10 in the prenatal restraint stress
      (RS) group and the prenatal restraint stress plus neonatal handling and
      environmental enrichment (RE) group compared to the negative control (NC) group.
      However, the expression of GAP-43 in RS pups was lower on P20 and P45 than that
      in NC and RE pups. Exposure to prenatal stress prolonged average latency and
      total swim distance, but neonatal handling and environmental enrichment could
      reverse the change. Differences were also observed in the selection of search
      strategies. These results indicate that neonatal handling and environmental
      enrichment can improve the spatial learning and memory ability of prenatally
      stressed offspring, and the possible mechanism is the upregulation of GAP-43.

PMID- 22617638
TI  - Home births in the United States, 1990-2009.
AB  - After 14 years of decline, the percentage of home births rose by 29% from 2004 to
      2009, to the point where it is at the highest level since data on this item began
      to be collected in 1989. The overall increase in home births was driven mostly by
      a 36% increase for non-Hispanic white women. About 1 out of every 90 births to
      non-Hispanic white women are now home births. The percentage of home births for
      non-Hispanic white women was three to five times higher than for any other racial
      or ethnic group. Home births have a lower risk profile than hospital births, with
      fewer births to teenagers or unmarried women, and with fewer preterm, low
      birthweight, and multiple births. The lower risk profile of home compared with
      hospital births suggests that home birth attendants are selecting low-risk women
      as candidates for home birth. The increase in the percentage of home births from
      2004 to 2009 was widespread and involved selected states from every region of the
      country. The large variations in the percentage of home births by state may be
      influenced by differences among states in laws pertaining to births are more
      prevalent among non-Hispanic white women (7). midwifery practice or out-of
      hospital birth (8,9), as well as by differences in the racial and ethnic
      composition of state populations, as home Studies have suggested that most home
      births are intentional or planned home births, whereas others are unintentional
      or unplanned, because of an emergency situation (i.e., precipitous labor, labor
      complications, or unable to get to the hospital in time) (3,6). Although not
      representative of all U.S. births (see "Data source and methods"), 87% of home
      births in a 26-state reporting area (comprising 50% of U.S. births) were planned
      in 2009. For non-Hispanic white women, 93% of home births were planned (10).
      Women may prefer a home birth over a hospital birth for a variety of reasons,
      including a desire for a low-intervention birth in a familiar environment
      surrounded by family and friends, and cultural or religious concerns (9,11). Lack
      of transportation in rural areas and cost factors may also play a role, as home
      births cost about one-third as much as hospital births (9,11,12).

PMID- 22617639
TI  - Atypical bilateral orbital metastases of lobular breast carcinoma.
AB  - Breast carcinoma metastasizing to the orbit is a well-recognized entity. The
      authors present a 50-year-old woman with bilateral upper and lower eyelid masses
      and generalized dysmotility. MRI showed gadolinium-enhancing homogenous soft
      tissue masses filling both orbits from the eyelids to the apex and a biopsy that
      confirmed metastatic breast carcinoma. To the authors' knowledge, orbital
      metastasis of breast carcinoma has never presented in this manner.

PMID- 22617640
TI  - Molecular biologic assessment of cutaneous specimens of ocular rosacea.
AB  - PURPOSE: To characterize the molecular biologic environment of pathological skin
      in ocular rosacea and to differentiate the levels of inflammatory molecules in
      ocular rosacea from those of normal skin. METHODS: The concentrations of 48
      molecules were assayed in cutaneous biopsies taken from patients with ocular
      rosacea and from normal controls. RESULTS: There were very few molecular
      differences between the 2 groups, and 43 of the 48 molecules that were measured
      in this study were not significantly different between the 2 groups. The
      concentrations of 5 molecules (interleukin-1beta, interleukin-16, stem cell
      factor, monocyte chemotactic protein-1, and monokine induced by gamma-interferon)
      were significantly enriched in ocular rosacea. CONCLUSIONS: Ocular rosacea is a
      highly ordered molecular process and involves elevations in the concentrations of
      specific molecules. The particular pattern of enrichment supports the notion that
      ocular rosacea represents a disorder of innate immunity. Furthermore, these
      molecules may represent novel therapeutic targets in the future management of
      this disorder.

PMID- 22617641
TI  - The modified Bick quick strip procedure for surgical treatment of eyelid
      malposition.
AB  - PURPOSE: To describe the quick strip technique, a hybrid procedure that combines
      features of the classic Bick procedure and lateral tarsal strip, and to evaluate
      its effectiveness for correction of lower eyelid malpositions due to horizontal
      laxity (including both ectropion and entropion). METHODS: Retrospective chart
      review of 225 eyelids of 160 patients receiving the quick strip. Patient
      demographics, results, complications, and symptomatic improvement were evaluated.
      Subgroups included 54 eyelids of 42 patients with entropion and 171 eyelids of
      118 patients with various degrees of ectropion. RESULTS: Complete resolution of
      eyelid malposition was achieved in 208/225 (92.4%) eyelids of 146/160 (91.3%)
      patients. Late recurrences occurred in 1/225 (0.4%) eyelids of 1/160 (0.6%)
      patients. Symptomatic improvement was achieved in 152/160 (95.0%) patients.
      Complications were infrequent with no cases of infection, hematoma, or lateral
      canthal rounding. The procedure can be combined in a straightforward manner with
      adjunctive procedures such as suborbicularis oculi fat lift and medial spindle
      for more advanced cases of ectropion. CONCLUSION: Quick Strip is an effective and
      efficient surgical treatment for the correction of eyelid malpositions that
      require horizontal tightening as a component of their management.

PMID- 22617642
TI  - Shrinkage revisited:  how long is long enough?
AB  - PURPOSE: Temporal artery biopsy (TAB) is considered the gold standard in the
      diagnosis of suspected giant cell arteritis. The most commonly accepted length
      for an adequate postfixation TAB specimen is 20 mm. There is a reported 2.4-mm
      mean shrinkage with the fixation process, but to date, there is no data
      correlating shrinkage after specimen fixation with the biopsy results. METHODS: A
      prospective, Institutional Review Board-approved study of all patients undergoing
      TAB over 1 year was performed. The pre- and postfixation measurements were
      recorded. Comparison of the pre- and postfixation lengths was performed, and
      potential correlation was sought with biopsy results and patient gender, age, and
      race/ethnicity. RESULTS: Sixty-two TABs were performed over a 1 year period with
      53 (85.5%) negative for giant cell arteritis. The mean shrinkage length was 4.61
      mm +/- 2.97 overall, and the amount of shrinkage between positive and negative
      TAB specimens was not significant (p = 0.43). Linear regression analysis did not
      show any correlation between the amount of shrinkage and the length of the
      specimen or duration in fixative. There was no significant difference between the
      amount of shrinkage by surgeon (p = 0.82), patient gender (p = 1.00), or
      race/ethnicity (p = 0.695). CONCLUSIONS: Surgeons should be aware of the amount
      of shrinkage of TAB specimens to meet the commonly accepted goal of 20 mm
      postfixation length. Based on the 4.61-mm mean shrinkage with 2.97-mm standard
      deviation, a 27.58-mm specimen would have to be obtained to reach the 20-mm goal.
      Surgeon, patient age, gender, race/ethnicity, and biopsy results did not have a
      significant impact on the amount of TAB specimen shrinkage.

PMID- 22617643
TI  - A novel technique of Jones tube fixation for refractory tube extrusion.
AB  - One of the major complications of conjunctivodacryocystorhinostomy is Jones tube
      extrusion postoperatively. Various tube modifications have been described to
      promote tube stability. While these variants have been shown to be successful; on
      occasion, tube extrusion can be recurrent, leading to patient and surgeon
      frustration and ongoing symptoms. In this case report the author's describe a
      method of Jones tube fixation which mechanically prevents tube extrusion.

PMID- 22617644
TI  - A solution to the Jones tube continuous positive airway pressure (CPAP) dilemma?
AB  - A 49-year-old woman, who had previously undergone bilateral Jones tube placement,
      began nasal continuous positive airway pressure for obstructive sleep apnea. The
      patient's use of continuous positive airway pressure was limited by intolerance
      of the transfer of air through the Jones tube to her ocular surface resulting in
      irritation and discomfort. A change from nasal continuous positive airway
      pressure to a full face mask, including both Jones tubes in the pressure circuit,
      resolved the problem.

PMID- 22617645
TI  - Tendon sheath fibroma of the medial canthal tendon.
AB  - Fibromas of the tendon sheath are slow-growing, benign tumors most commonly found
      on the hands and wrist. A fibroma of the tendon sheath arising from the medial
      canthal tendon presented as an enlarging nodule that had been present for 40
      years. The fibroma was identified by microscopy and immunohistochemistry, and
      surgical resection appears to have been curative.

PMID- 22617646
TI  - Extramedullary hematopoietic lesion of the orbit presenting as a ring enhancing
      lesion.
AB  - A 47-year-old healthy man presented with symptoms of double vision and drooping
      of the right upper eyelid. Examination disclosed signs of vertical diplopia and
      right upper-eyelid ptosis. An MRI delineated a well circumscribed, ring enhancing
      mass within the right orbit. The mass with peripheral enhancement located within
      the orbit, generated a broad differential diagnosis. After an excisional biopsy
      was performed, the mass was revealed to be fibrosis with extramedullary
      hematopoiesis. Current differential diagnoses of ring enhancing orbital lesions
      do not include extramedullary hematopoiesis, but we present a unique presentation
      of extramedullary hematopoiesis presenting as a ring enhancing orbital mass.

PMID- 22617647
TI  - Prolonged gaseous hypothermia prevents the upregulation of phagocytosis-specific
      protein annexin 1 and causes low-amplitude EEG activity in the aged rat brain
      after cerebral ischemia.
AB  - In aged humans, stroke is a major cause of disability for which no
      neuroprotective measures are available. In animal studies of focal ischemia,
      short-term hypothermia often reduces infarct size. Nevertheless, efficient
      neuroprotection requires long-term, regulated lowering of whole-body temperature.
      Previously, we reported that post-stroke exposure to hydrogen sulfide (H(2)S)
      effectively lowers whole-body temperature and confers neuroprotection in aged
      animals. In the present study using magnetic resonance imaging,
      electroencephalogram recording, DNA arrays, reverse transcriptase polymerase
      chain reaction, western blotting and immunofluorescence, we characterized the
      central nervous system response to H(2)S-induced hypothermia and report, for the
      first time, that annexin A1, a major pro-inflammatory protein that is upregulated
      after stroke, was consistently downregulated in polymorphonuclear cells in the
      peri-lesional cortex of post-ischemic, aged rat brain after 48 hours of
      hypothermia induced by exposure to H(2)S. Our data suggest that long-term
      hypothermia may be a viable clinical approach to protecting the aged brain from
      cerebral injury. Our findings further suggest that, in contrast to monotherapies
      that have thus far uniformly failed in clinical practice, hypothermia has
      pleiotropic effects on brain physiology that may be necessary for effective
      protection of the brain after stroke.

PMID- 22617648
TI  - Reproducibility of cerebral blood flow assessment using a quantitative SPECT
      reconstruction program and split-dose 123I-iodoamphetamine in institutions with
      different gamma-cameras and collimators.
AB  - Single photon emission computed tomography (SPECT) is used widely in clinical
      studies. However, the technique requires image reconstruction and the methods for
      correcting scattered radiation and absorption are not standardized among SPECT
      procedures. Therefore, quantitation of cerebral blood flow (CBF) may not be
      constant across SPECT models. The quantitative SPECT (QSPECT) software package
      has been developed for standardization of CBF. Using the QSPECT/dual-table
      autoradiographic (DTARG) method, CBF and cerebral vascular reactivity (CVR) at
      rest and after acetazolamide challenge can be evaluated using (123)I
      iodoamphetamine in a single SPECT session. In this study, we examined the
      reproducibility of quantitative regional CBF and CVR in QSPECT/DTARG using
      different SPECT models at two facilities. The subjects were nine patients with
      chronic cerebral ischemic disease who underwent QSPECT/DTARG at both facilities
      with use of different gamma-cameras and collimators. There were significant
      correlations for CBF at rest and after acetazolamide challenge measured at the
      two facilities. The consistency of the CBFs of the patients measured at the two
      facilities were good in all cases. Our results show that CBF measured by
      QSPECT/DTARG in the same patients is reproducible in different SPECT models. This
      indicates that standardized evaluation of CBF can be performed in large
      multicenter studies.

PMID- 22617649
TI  - Aspartoacylase supports oxidative energy metabolism during myelination.
AB  - The inherited leukodystrophy Canavan disease arises due to a loss of the ability
      to catabolize N-acetylaspartic acid (NAA) in the brain and constitutes a major
      point of focus for efforts to define NAA function. Accumulation of noncatabolized
      NAA is diagnostic for Canavan disease, but contrasts with the abnormally low NAA
      associated with compromised neuronal integrity in a broad spectrum of other
      clinical conditions. Experimental evidence for NAA function supports a role in
      white matter lipid synthesis, but does not explain how both elevated and lowered
      NAA can be associated with pathology in the brain. We have undertaken a
      systematic analysis of postnatal development in a mouse model of Canavan disease
      that delineates development and pathology by identifying markers of oxidative
      stress preceding oligodendrocyte loss and dysmyelination. These data suggest a
      role for NAA in the maintenance of metabolic integrity in oligodendrocytes that
      may be of relevance to the strong association between NAA and neuronal viability.
      N-acetylaspartic acid is proposed here to support lipid synthesis and energy
      metabolism via the provision of substrate for both cellular processes during
      early postnatal development.

PMID- 22617650
TI  - Comparative genomics analysis of five families of antimicrobial peptide-like
      genes in seven ant species.
AB  - Ants, as eusocial insects, live in dense groups with high connectivity,
      increasing the risk of pathogen spread and possibly driving the evolution of
      their antimicrobial immune system. Draft genomes of seven ant species provide a
      new source to undertake comparative study of their antimicrobial peptides (AMPs),
      key components of insect innate immunity. By using computational approaches, we
      analyzed five AMP families that include abaecins, hymenoptaecins, insect
      defensins, tachystatins, and crustins in ants, which comprise 69 new members.
      Among them, a new type of proline-rich abaecins was recognized and they are
      exclusively present in ants. Hymenoptaecins, a family of glycine-rich AMPs from
      Hymenoptera and Diptera, exhibit variable numbers of intragenic tandem repeats in
      a lineage-specific manner and all hymenoptaecins in ants have evolved an acidic C
      terminal propeptide. In some ant species, insect defensins with the cysteine
      stabilized alpha-helical and beta-sheet (CSalphabeta) fold and tachystatin-like
      AMPs with the inhibitor cysteine knot (ICK) fold have undergone gene expansion
      and differential gene loss. Moreover, extensive sequence diversity exists in the
      C-termini of the defensins and the ICK-type peptides and the n-loop of the
      defensins. Also, we identified for the first time a crustin-type AMP in ants,
      which are only known in crustaceans previously. These ant crustins evolutionarily
      gain an aromatic amino acid-rich insertion when compared with those of
      crustaceans. Our work not only enlarges the insect AMP resource, but also sheds
      light on the complexity and dynamic evolution of AMPs in ants.

PMID- 22617652
TI  - Prime elements of subjectively experienced feelings and desires: imaging the
      emotional cocktail.
AB  - Primary affects exist at an ecological-communicative level of analysis, and
      therefore are not identifiable with specific brain regions. The constructionist
      view favored in the target article, that emotions emerge from "more basic
      psychological processes," does not specify the nature of these processes. These
      more basic processes may actually involve specific neurochemical systems, that
      is, primary motivational-emotional systems (primes), associated with specific
      feelings and desires that combine to form the "cocktail" of experienced emotion.

PMID- 22617653
TI  - Understanding emotion: lessons from anxiety.
AB  - We agree that conceptualisation is key in understanding the brain basis of
      emotion. We argue that by conflating facial emotion recognition with subjective
      emotion experience, Lindquist et al. understate the importance of biological
      predisposition in emotion. We use examples from the anxiety disorders to
      illustrate the distinction between these two phenomena, emphasising the
      importance of both emotional hardware and contextual learning.

PMID- 22617654
TI  - Overcoming the emotion experience/expression dichotomy.
AB  - We challenge the classic experience/expression dichotomous account of emotions,
      according to which experiencing and expressing an emotion are two independent
      processes. By endorsing Dewey's and Mead's accounts of emotions, and capitalizing
      upon recent empirical findings, we propose that expression is part of the
      emotional experience. This proposal partly challenges the purely constructivist
      approach endorsed by the authors of the target article.

PMID- 22617655
TI  - A constructionist account of emotional disorders.
AB  - Lindquist et al. present a strong case for a constructionist account of emotion.
      First, we elaborate on the ramifications that a constructionist account of
      emotions might have for psychiatric disorders with emotional disturbances as core
      elements. Second, we reflect on similarities between Lindquist et al.'s model and
      recent attempts at formulating psychiatric disorders as networks of causally
      related symptoms.

PMID- 22617656
TI  - Emotions as mind organs.
AB  - In matters of the mind, the opposition between what is mind-made or inside and
      natural or outside the mind is bound to misfire. Lindquist et al. build their
      analysis on a strong contrast between naturalism, which they reject, and
      psychologism, which they endorse. We challenge this opposition and indicate how
      adopting psychologism to combat a naturalistic view of emotional mind/brain areas
      is self-defeating. We briefly develop the alternative view of emotions as mental
      organs.

PMID- 22617657
TI  - A rigorous approach for testing the constructionist hypotheses of brain function.
AB  - Although the target article provides strong evidence against the locationist
      view, evidence for the constructionist view is inconclusive, because co
      activation of brain regions does not necessarily imply connectivity between them.
      We propose a rigorous approach wherein connectivity between co-activated regions
      is first modeled using exploratory Granger causality, and then confirmed using
      dynamic causal modeling or Bayesian modeling.

PMID- 22617658
TI  - Emotional participation in musical and non-musical behaviors.
AB  - Existence of similarities of overall brain activation, specifically during
      emotional and other common psychological operations (discussed by Lindquist et
      al.), supports a proposal that emotion participates continuously in dynamic
      adjustment of behavior. The proposed participation can clarify the relationship
      of emotion to musical experience. Music, in turn, can help explore such
      participation.

PMID- 22617659
TI  - What can neuroimaging meta-analyses really tell us about the nature of emotion?
AB  - In Vytal and Hamann (2010) we reported a neuroimaging meta-analysis that found
      that basic emotions can be distinguished by their brain activation correlates, in
      marked contrast to Lindquist et al.'s conclusions in the target article. Here, I
      discuss implications of these findings for understanding emotion, outline
      limitations of using meta-analyses and neuroimaging as the sole basis for
      deciding between emotion views, and suggest that these views are essentially
      compatible and could be adapted and combined into an integrated emotion
      framework.

PMID- 22617651
TI  - The brain basis of emotion: a meta-analytic review.
AB  - Researchers have wondered how the brain creates emotions since the early days of
      psychological science. With a surge of studies in affective neuroscience in
      recent decades, scientists are poised to answer this question. In this target
      article, we present a meta-analytic summary of the neuroimaging literature on
      human emotion. We compare the locationist approach (i.e., the hypothesis that
      discrete emotion categories consistently and specifically correspond to distinct
      brain regions) with the psychological constructionist approach (i.e., the
      hypothesis that discrete emotion categories are constructed of more general brain
      networks not specific to those categories) to better understand the brain basis
      of emotion. We review both locationist and psychological constructionist
      hypotheses of brain-emotion correspondence and report meta-analytic findings
      bearing on these hypotheses. Overall, we found little evidence that discrete
      emotion categories can be consistently and specifically localized to distinct
      brain regions. Instead, we found evidence that is consistent with a psychological
      constructionist approach to the mind: A set of interacting brain regions commonly
      involved in basic psychological operations of both an emotional and non-emotional
      nature are active during emotion experience and perception across a range of
      discrete emotion categories.

PMID- 22617660
TI  - Psychological constructionism and cultural neuroscience.
AB  - Lindquist et al. argue that emotional categories do not map onto distinct regions
      within the brain, but rather, arise from basic psychological processes, including
      conceptualization, executive attention, and core affect. Here, we use examples
      from cultural neuroscience to argue that psychological constructionism, not
      locationism, captures the essential role of emotion in the social and cultural
      brain.

PMID- 22617661
TI  - Further routes to psychological constructionism.
AB  - In this commentary, we do two things. First, we sketch two further routes to
      psychological constructionism. They are complementary to Lindquist et al.'s meta
      analyses and have potential to add new evidence. Second, we look at a challenging
      kind of case for constructionism, namely, emotional anomalies where there are
      correlated, and probably relevant, brain anomalies. Psychopaths are our example.

PMID- 22617662
TI  - Scaffolding emotions and evolving language.
AB  - We suggest that, in animals, the core-affect system is linked to partially
      assimilated behavioral dispositions that act as developmental scaffolds for the
      ontogenetic construction of emotions. We also propose that in humans the
      evolution of language altered the control of emotions, leading to categories that
      can be adequately captured only by emotion-words.

PMID- 22617663
TI  - The sleeping brain and the neural basis of emotions.
AB  - In addition to active wake, emotions are generated and experienced in a variety
      of functionally different states such as those of sleep, during which external
      stimulation and cognitive control are lacking. The neural basis of emotions can
      be specified by regarding the multitude of emotion-related brain states, as well
      as the distinct neuro- and psychodynamic stages (generation and regulation) of
      emotional experience.

PMID- 22617664
TI  - Emotion and personality factors influence the neural response to emotional
      stimuli.
AB  - Lindquist et al. assess the neural evidence for locationist versus psychological
      construction accounts of human emotion. A wealth of experimental and clinical
      investigations show that individual differences in emotion and personality
      influence emotion processing. These factors may also influence the brain's
      response to emotional stimuli. A synthesis of the relevant neuroimaging data must
      therefore take these factors into consideration.

PMID- 22617665
TI  - Emotions of "higher" cognition.
AB  - The target article by Lindquist et al. considers discrete emotions. This
      commentary argues that these are but a minor part of human emotional abilities,
      unifying us with animals. Uniquely human emotions are aesthetic emotions related
      to the need for the knowledge of "high" cognition, including emotions of the
      beautiful, cognitive dissonances, and musical emotions. This commentary touches
      on their cognitive functions and origins.

PMID- 22617666
TI  - Beyond brain regions: network perspective of cognition-emotion interactions.
AB  - Lindquist et al. provide a convincing case against what they call the locationist
      account of emotion. Their quantitative approach elegantly illustrates the
      shortcomings of this still-entrenched viewpoint. Here, I discuss how a network
      perspective will advance our understanding of structure-function mappings in
      general, and the relationship between emotion and cognition in the brain.

PMID- 22617667
TI  - The construction of emotional experience requires the integration of implicit and
      explicit emotional processes.
AB  - Although we agree that a constructivist approach to emotional experience makes
      sense, we propose that implicit (visceromotor and somatomotor) emotional
      processes are dissociable from explicit (attention and reflection) emotional
      processes, and that the conscious experience of emotion requires an integration
      of the two. Assessments of implicit emotion and emotional awareness can be
      helpful in the neuroscientific investigation of emotion.

PMID- 22617668
TI  - A systems approach to the brain basis of emotion also needs developmental and
      locationist views - the case of Tourette's syndrome.
AB  - The closeness of somatosensory phenomena and emotional states can be critically
      extended into a clinical perspective by referring to Tourette's Syndrome (TS).
      Two examples are discussed in this commentary: (1) the neurodevelopmental
      approach to the pre- and post-tic sensorimotor urges, and (2) the TS treatment
      with deep brain stimulation. It is shown that in TS, both views (locationist and
      constructionist) need to be combined along the lifespan in order to get a more
      realistic picture of the brain basis of emotion.

PMID- 22617669
TI  - The role of the amygdala in the appraising brain.
AB  - Lindquist et al. convincingly argue that the brain implements psychological
      operations that are constitutive of emotion rather than modules subserving
      discrete emotions. However, the nature of such psychological operations is open
      to debate. I argue that considering appraisal theories may provide alternative
      interpretations of the neuroimaging data with respect to the psychological
      operations involved.

PMID- 22617670
TI  - Functional specialization does not require a one-to-one mapping between brain
      regions and emotions.
AB  - Lindquist et al. have assumed that functional specialization requires a one-to
      one mapping between brain regions and discrete emotions. This assumption is in
      tension with the fact that regions can have multiple functions in the context of
      different, possibly distributed, networks. Once we open the door to other forms
      of functional specialization, neuroimaging data no longer favor constructionist
      models over natural kind models.

PMID- 22617671
TI  - Neuroscience findings are consistent with appraisal theories of emotion; but does
      the brain "respect" constructionism?
AB  - I reject Lindquist et al.'s implicit claim that all emotion theories other than
      constructionist ones subscribe to a "brain locationist" approach. The neural
      mechanisms underlying relevance detection, reward, attention, conceptualization,
      or language use are consistent with many theories of emotion, in particular
      componential appraisal theories. I also question the authors' claim that the meta
      analysis they report provides support for the specific assumptions of
      constructionist theories.

PMID- 22617672
TI  - A rapprochement between emotion and cognition: amygdala, emotion, and self
      relevance in episodic-autobiographical memory.
AB  - Lindquist et al. remark that not all fear instances lead to heightened amygdalar
      activity and, instead, point to roles of the amygdala in detecting
      "motivationally salient "or "emotionally impactful" stimuli. By reviewing
      research on the amygdala's functions in episodic-autobiographical memory, we
      further emphasize the involvement of the amygdala in coding the subjective
      relevance and extracting the biological and social significance of the stimuli.

PMID- 22617673
TI  - Invariants of human emotion.
AB  - Because of the complexity of human emotional responses, invariants must be sought
      not in the responses themselves, but in their generating mechanisms. Lindquist et
      al. show that functional locationism is a theoretical dead end; their proposed
      mechanistic framework is a first step toward better models of emotional behavior.
      We caution, however, that emotions may still be quasi-natural perceptual types.

PMID- 22617674
TI  - Feeling the strain: predicting the third dimension of core affect.
AB  - This commentary (1) raises the question about the possible conflation of core
      affect with the neural representation of interoceptive changes in regard to
      whether biological value is subpersonal or must be experienced, and (2) proposes
      that Wundt's third dimension of core affect - strain-relaxation - can be
      accounted for in the target model under a generalised predictive model of
      attention.

PMID- 22617675
TI  - What's in a baby-cry? Locationist and constructionist frameworks in parental
      brain responses.
AB  - Parental brain responses to baby stimuli constitute a unique model to study brain
      basis frameworks of emotion. Results for baby-cry and picture stimuli may fit
      with both locationist and psychological constructionist hypotheses. Furthermore,
      the utility of either model may depend on postpartum timing and relationship.
      Endocrine effects may also be critical for accurate models to assess mental
      health risk and treatment.

PMID- 22617676
TI  - Narrative constructions and the life history issue in brain-emotions relations.
AB  - Emotional reactions are rather flexible, due to the schema-like organization of
      complex socio-emotional situations. Some data on emotion development, and on
      certain pathological conditions such as alexithymia, give further support for the
      psychological constructivist view put forward by Lindquist et al. Narrative
      organization is a key component of this schematic organization. The self-related
      nature of narrative organization provides scaffolding to the contextual
      dependency of emotions.

PMID- 22617677
TI  - Neuronal deactivation is equally important for understanding emotional
      processing.
AB  - In their analyses of the neural correlates of discrete emotionality, Lindquist et
      al. do not consider the numerous drawbacks to inferring psychological processes
      based on currently available cognitive neurometric technology. The authors also
      disproportionately emphasize the relevance of neuronal activation over
      deactivation, which, in our opinion, limits the scope and utility of their
      conclusions.

PMID- 22617678
TI  - Timing: A missing key ingredient in typical fMRI studies of emotion.
AB  - Lindquist et al. provide a compelling summary of the brain bases of the onset of
      emotion. Their conclusions, however, are constrained by typical fMRI techniques
      that do not assess a key ingredient in emotional experience - timing. We discuss
      the importance of timing in theories of emotion as well as the implications of
      neural temporal dynamics for psychological constructionism.

PMID- 22617679
TI  - Need for more evolutionary and developmental perspective on basic emotional
      mechanisms.
AB  - Lindquist et al.'s meta-analysis focuses on adult humans; the authors' emotion
      model might be strengthened by considering research on infants and animals,
      highlighting the importance of the limbic system. Reliance on the James-Lange
      theory is questionable; emotions typically occur instantaneously, with dubious
      dependence on bodily feedback for affect. Stronger evidence for localization
      might be obtained using more precise emotion terms and alterative localization
      methods.

PMID- 22617682
TI  - Autocrine CCL2 promotes cell migration and invasion via PKC activation and
      tyrosine phosphorylation of paxillin in bladder cancer cells.
AB  - The amount of monocyte chemoattractant protein-1 (MCP-1/CCL2) produced by a
      transitional cell carcinoma is directly correlated with high recurrence and poor
      prognosis in bladder cancer. However, the mechanisms underlying the effects of
      CCL2 on tumor progression remain unexplored. To investigate the role played by
      CCL2, we examined cell migration in various bladder cancer cell lines. We found
      that high-grade cancer cells expressing high levels of CCL2 showed more migration
      activity than low-grade bladder cancer cells expressing low levels of the
      chemokine. Although the activation of CCL2/CCR2 signals did not appreciably
      affect cell growth, it mediated cell migration and invasion via the activation of
      protein kinase C and phosphorylation of tyrosine in paxillin. Blocking CCL2 and
      CCR2 with small hairpin RNA (shCCL2) or a specific inhibitor reduced CCL2/CCR2
      mediated cell migration. The antagonist of CCR2 promoted the survival of mice
      bearing MBT2 bladder cancer cells, and CCL2-depleted cells showed low
      tumorigenicity compared with shGFP cells. In addition to observing high-levels of
      CCL2 in high-grade human bladder cancer cells, we showed that the CCL2/CCR2
      signaling pathway mediated migratory and invasive activity, whereas blocking the
      pathway decreased migration and invasion. In conclusion, high levels of CCL2
      expressed in bladder cancer mediates tumor invasion and is involved with advanced
      tumorigenesis. Our findings suggest that this CCL2/CCR2 pathway is a potential
      candidate for the attenuation of bladder cancer metastases.

PMID- 22617680
TI  - High-resolution functional magnetic resonance imaging methods for human midbrain.
AB  - Functional MRI (fMRI) is a widely used tool for non-invasively measuring
      correlates of human brain activity. However, its use has mostly been focused upon
      measuring activity on the surface of cerebral cortex rather than in subcortical
      regions such as midbrain and brainstem. Subcortical fMRI must overcome two
      challenges: spatial resolution and physiological noise. Here we describe an
      optimized set of techniques developed to perform high-resolution fMRI in human
      SC, a structure on the dorsal surface of the midbrain; the methods can also be
      used to image other brainstem and subcortical structures. High-resolution (1.2 mm
      voxels) fMRI of the SC requires a non-conventional approach. The desired spatial
      sampling is obtained using a multi-shot (interleaved) spiral acquisition (1).
      Since, T(2)* of SC tissue is longer than in cortex, a correspondingly longer echo
      time (T(E) ~ 40 msec) is used to maximize functional contrast. To cover the full
      extent of the SC, 8-10 slices are obtained. For each session a structural anatomy
      with the same slice prescription as the fMRI is also obtained, which is used to
      align the functional data to a high-resolution reference volume. In a separate
      session, for each subject, we create a high-resolution (0.7 mm sampling)
      reference volume using a T(1)-weighted sequence that gives good tissue contrast.
      In the reference volume, the midbrain region is segmented using the ITK-SNAP
      software application (2). This segmentation is used to create a 3D surface
      representation of the midbrain that is both smooth and accurate (3). The surface
      vertices and normals are used to create a map of depth from the midbrain surface
      within the tissue (4). Functional data is transformed into the coordinate system
      of the segmented reference volume. Depth associations of the voxels enable the
      averaging of fMRI time series data within specified depth ranges to improve
      signal quality. Data is rendered on the 3D surface for visualization. In our lab
      we use this technique for measuring topographic maps of visual stimulation and
      covert and overt visual attention within the SC (1). As an example, we
      demonstrate the topographic representation of polar angle to visual stimulation
      in SC.

PMID- 22617683
TI  - The role of the kidney in the systemic elimination of interleukin 6, platelet
      derived growth factor and transforming growth factor beta.
AB  - STUDY GOAL: The aim of the study was to assess the role of the kidney in systemic
      elimination of IL-6 and growth factors (PDGF, TGF-beta) by comparison of their
      concentrations in renal arteries and veins, peripheral veins and urine. MATERIAL
      AND METHODS: 30 brain-dead kidney donors were included in the study. Samples were
      obtained during the harvesting procedure. 10 healthy volunteers served as
      controls. A mathematical model of elimination of investigated proteins from
      systemic circulation was developed. The elimination ratio (ER) formula indicates
      the predominance of renal synthesis or degradation and also quantifies the renal
      uptake (UR) and renal pass (PR) of investigated proteins. Serum levels of
      investigated proteins were estimated using an immunoenzymatic method (ELISA).
      RESULTS: Renal IL-6 uptake ratio (UR) amounted to 6.6%, elimination ratio (ER)
      amounted to 6.4% and pass ratio (PR) amounted to 0.2%. PDGF ratios amounted to
      5.1%, 5.0% and 0.1% and TGF-beta ratios amounted to -9%, -9% and 0%,
      respectively. CONCLUSIONS: The kidney takes part in the elimination of IL-6 and
      PDGF from systemic circulation. The kidney does not take part in the elimination
      of TGF-beta.

PMID- 22617685
TI  - Biotechnology for enhancing plant production and food quality: IBS 2010 part III.

PMID- 22617684
TI  - B cell-associated immune profiles in patients with end-stage renal disease
      (ESRD).
AB  - Most of the previous studies on immune dysregulation in end-stage renal disease
      (ESRD) have focused on T cell immunity. We investigated B cell subpopulations in
      ESRD patients and the effect of hemodialysis (HD) on B cell-associated immune
      profiles in these patients. Forty-four ESRD [maintenance HD patients (n = 27) and
      pre-dialysis patients (n = 17)] and 27 healthy volunteers were included in this
      study. We determined the percentage of B cell subtypes, such as mature and
      immature B cells, memory B cells, and interleukin (IL)-10+ cells, as well as B
      cell-producing cytokines (IL-10, IL-4 and IL-21) by florescent activated cell
      sorting (FACS). B cell-associated gene expression was examined using real-time
      PCR and B cell producing cytokines (IL-10, IL-4 and IL-21) were determined using
      an enzyme- linked immunosorbent assay (ELISA). The percentage of total B cells
      and mature B cells did not differ significantly among the three groups. The
      percentages of memory B cells were significantly higher in the pre-dialysis group
      than in the HD group (P < 0.01), but the percentage of immature B cells was
      significantly lower in the pre-dialysis group than in the other groups. The
      percentages of IL-10-expressing cells that were CD19+ or immature B cells did not
      differ significantly (P > 0.05) between the two subgroups within the ESRD group,
      but the serum IL-10 concentration was significantly lower in the pre-dialysis
      group (P < 0.01). The results of this study demonstrate significantly altered B
      cell-associated immunity. Specifically, an imbalance of immature and memory B
      cells in ESRD patients was observed, with this finding predominating in pre
      dialysis patients.

PMID- 22617686
TI  - Role of K(+) binding residues in stabilization of heme spin state of Leishmania
      major peroxidase.
AB  - The endogenous cation in peroxidases may contribute to the type of heme
      coordination. Here a series of ferric and ferrous derivatives of wild-type
      Leishmania major peroxidase (LmP) and of engineered K(+) site mutants of LmP,
      lacking potassium cation binding site, has been examined by electronic absorption
      spectroscopy at 25 degrees C. Using UV-visible spectrophotometry, we show that
      the removal of K(+) binding site causes substantial changes in spin states of
      both the ferric and ferrous forms. The spectral changes are interpreted to be,
      most likely, due to the formation of a bis-histidine coordination structure in
      both the ferric and ferrous oxidation states at neutral pH 7.0. Stopped flow
      spectrophotometric techniques revealed that characteristics of Compound I were
      not observed in the K(+) site double mutants in the presence of H(2)O(2).
      Similarly electron donor oxidation rate was two orders less for the K(+) site
      double mutants compared to the wild type. These data show that K(+) functions in
      preserving the protein structure in the heme surroundings as well as the spin
      state of the heme iron, in favor of the enzymatically active form of LmP.

PMID- 22617687
TI  - Cohort profile: the Young Lives study.
AB  - Young Lives is an international longitudinal study investigating the changing
      nature of childhood poverty in four low-income countries [Ethiopia, India (Andhra
      Pradesh), Peru and Vietnam] over a 15-year period. In each country, the cohort is
      comprised of ~ 2000 children aged between 6 and 18 months and up to 1000 children
      aged between 7 and 8 years, recruited in 2002 and sampled from 20 sentinel sites.
      The first survey data collection from primary caregivers and older children took
      place in 2002, the second in 2006-07 and the third in 2009-10. Data on the
      community contexts were collected to complement the household surveys. To
      elaborate and extend the quantitative data, longitudinal qualitative research
      with a subgroup of the children was carried out in 2007, 2008 and 2010-11. Topic
      areas covered included nutrition, health and well-being, cognitive and physical
      development, health behaviours and education, as well as the social, demographic
      and economic status of the household. Survey data from the study are archived in
      the International Section of the UK Public Data Archive.

PMID- 22617688
TI  - HIV-malaria co-infection: effects of malaria on the prevalence of HIV in East sub
      Saharan Africa.

PMID- 22617689
TI  - Status of epidemiology in the WHO South-East Asia region: burden of disease,
      determinants of health and epidemiological research, workforce and training
      capacity.
AB  - BACKGROUND: The South-East Asia region (SEAR) accounts for one-quarter of the
      world's population, 40% of the global poor and ~30% of the global disease burden,
      with a disproportionately large share of tuberculosis (35%), injuries (30%),
      maternal (33%) and <5-year-old mortality (30%). In this article, we describe the
      disease burden and status of epidemiological research and capacity in the SEAR to
      understand, analyse and develop capacity in response to the diverse burdens of
      diseases in the region. METHODS: Data on morbidity, mortality, risk factors,
      social determinants, research capacity, health education, workforce and systems
      in the SEAR were obtained using global data on burden of disease, peer-reviewed
      journals, World Health Organization (WHO) technical and advisory reports, and
      where available, validated country reports and key informants from the region.
      RESULTS: SEAR countries are afflicted with a triple burden of disease-infectious
      diseases, non-communicable diseases and injuries. Of the seven WHO regions, SEAR
      countries account for the highest proportion of global mortality (26%) and due to
      relatively younger ages at death, the second highest percentage of total years of
      life lost (30%). The SEAR exceeds the global average annual mortality rate for
      all three broad cause groupings-communicable, maternal, perinatal and nutritional
      conditions (334 vs 230 per 100 000); non-communicable diseases (676 vs 573 per
      100 000); and injuries (101 vs 78 per 100 000). Poverty, education and other
      social determinants of health are strongly linked to inequities in health among
      SEAR countries and within socio-economic subgroups. India, Thailand and
      Bangladesh produce two-thirds of epidemiology publications in the region.
      Significant efforts to increase health workforce capacity, research and training
      have been undertaken in the region, yet considerable heterogeneity in resources
      and capacity remains. CONCLUSIONS: Health systems, statistics and surveillance
      programmes must respond to the demographic, economic and epidemiological
      transitions that define the current disease burden and risk profile of SEAR
      populations. Inequities in health must be critically analysed, documented and
      addressed through multi-sectoral approaches. There is a critical need to improve
      public health intelligence by building epidemiological capacity in the region.

PMID- 22617691
TI  - The intersection of evidence-based practice with 5 quality improvement
      methodologies.
AB  - In this department, the authors highlight hot topics in nursing outcomes,
      research, and evidence-based practice relevant to the nurse administrator. The
      goal is to discuss the practical implications for nurse leaders in diverse
      healthcare settings. Content includes evidence-based projects and decision
      making, locating measurement tools for quality improvement and safety projects,
      using outcome measures to evaluate quality, practice implications of
      administrative research, and exemplars of projects that demonstrate innovative
      approaches to organizational problems. In this article, the authors describe the
      intersection of various quality improvement methodologies with the evidence-based
      practice process. Five quality improvement approaches, plan-do-check-act, Six
      Sigma, Lean, root cause analysis, and failure mode effects analysis, are
      described and are used to frame examples.

PMID- 22617692
TI  - Nurse leaders in healthcare design.
AB  - Nurses are leading major changes in the healthcare design and construction
      industry. The purpose of this facility design article is to expand nurse leaders'
      knowledge and competencies in health facility design and enable them to take
      leadership roles in design efforts. This article describes how a group of
      determined and passionate nurses have created significant changes in healthcare
      design.

PMID- 22617693
TI  - Transformational leadership: the art of advocacy and influence.

PMID- 22617694
TI  - Cultivating strategic thinking skills.
AB  - This department highlights change management strategies that may be successful in
      strategically planning and executing organizational change initiatives. With the
      goal of presenting practical approaches helpful to nurse leaders advancing
      organizational change, content includes evidence-based projects, tools, and
      resources that mobilize and sustain organizational change initiatives. In this
      article, the author presents an overview of strategic leadership and offers
      approaches for cultivating strategic thinking skills.

PMID- 22617695
TI  - Nursing shared governance: leading a journey of excellence.
AB  - This article describes how a community hospital engaged nurses through the
      nursing shared governance model to select a PPM that aligned nursing values and
      priorities with the organization's vision and mission.

PMID- 22617696
TI  - Influencing nursing education, policy, practice, and research: an interview with
      Kathleen Potempa. Interview by Jeffrey M. Adams.
AB  - This department highlights nursing leaders who have demonstrated a commitment to
      leading change. This interview, profiles the experience insights, vision, and
      thoughts of Kathleen Potempa, PhD, RN, FAAN, President of the American
      Association of Colleges of Nursing (AACN) and Dean of the University of Michigan
      School of Nursing.

PMID- 22617697
TI  - Nursing care, inpatient satisfaction, and value-based purchasing: vital
      connections.
AB  - OBJECTIVE: The objective of this study was to investigate how domains of patient
      satisfaction in hospitals predict Hospital Consumer Assessment of Healthcare
      Providers and Systems (HCAHPS) global rating scores to support hospital
      administrators in dealing with reimbursement changes. BACKGROUND: Medicare's
      inpatient value-based purchasing program ties a portion of hospital payments to
      scores on the HCAHPS survey. METHODS: Logistical regression analysis of patient
      level satisfaction domain scores from a standard, commercially available survey
      and HCAHPS top-box scores controlled for potential confounding variables.
      RESULTS: Each 1-point increase in the nursing domain score increased the odds of
      achieving an HCAHPS top-box score by 4.9%. Increases in other domain scores also
      affected top-box odds, although to a smaller extent. CONCLUSIONS: Hospital
      administrators wishing to maximize Medicare reimbursement will realize the
      greatest impact by improving patient satisfaction with nursing care.

PMID- 22617698
TI  - Hourly rounding implementation: a multisite description of structures, processes,
      and outcomes.
AB  - OBJECTIVE: This study identifies structures, processes, and outcomes associated
      with hourly nurse rounding. BACKGROUND: Literature supports that nurse rounding
      every 1 to 2 hours affects quality outcomes. Evidence is lacking regarding the
      process of successful implementation. METHODS: Using an action research design,
      project leads implementing hourly rounding at 11 Southern California hospitals
      agreed to recorded telephone interviews. Transcribed interviews underwent content
      analysis. RESULTS: Analysis revealed 15 major themes. Structure themes include
      use of rounding behaviors described through an acronym and collaborative phone
      call. Processes include a library of tools to use incorporating both patient and
      staff feedback. Patient satisfaction and patient perception of being well cared
      for are 2 common outcome themes. CONCLUSIONS: This study provides evidence that
      frequent reevaluation of structures and processes promote achievement of desired
      outcomes in relation to hourly rounding. The authors recommend abandonment of
      routinization and adoption of flexibility to sustain successful implementation of
      hourly rounding.

PMID- 22617699
TI  - The relationship-based care model: evaluation of the impact on patient
      satisfaction, length of stay, and readmission rates.
AB  - OBJECTIVE: The objective of this study was to assess the impact of the
      implementation of the relationship-based care (RBC) model on patient
      satisfaction, length of stay, and readmission rates in hospitalized patients.
      BACKGROUND: RBC model promotes organizational viability in critical areas that
      measure success, inclusive of clinical quality, patient satisfaction, and robust
      financial standing. METHODS: A retrospective secondary analysis of aggregate
      patient satisfaction data, length of stay, and readmission rates at a rural Texas
      hospital was reviewed for the years 2009 and 2010. This study compared
      preimplementation data for year 2009 with postimplementation data for year 2010.
      RESULTS: Data support the positive influential impact of RBC model. A negative
      correlation was noted with readmission rates and a concomitant positive
      correlation with length of stay. Overall satisfaction with nursing did not reveal
      a significant correlation to the new care model. CONCLUSIONS: RBC model supports
      a patient-centered, collaborative care environment, maximizing potential
      reimbursement.

PMID- 22617700
TI  - Nursing sabbatical in the acute care hospital setting: a cost-benefit analysis.
AB  - Practice-based acute care nurses experience a high incidence of burnout and
      dissatisfaction impacting retention and innovation and ultimately burdening the
      financial infrastructure of a hospital. Business, industry, and academia have
      successfully implemented professional sabbaticals to retain and revitalize
      valuable employees; however, the use is infrequent among acute care hospitals.
      This article expands upon the synthesis of evidence supporting nursing
      sabbaticals and suggests this option as a fiscally sound approach for nurses
      practicing in the acute care hospital setting. A cost-benefit analysis and human
      capital management strategies supporting nursing sabbaticals are identified.

PMID- 22617701
TI  - Experience-dependent expression of rat hippocampal Arc and Homer 1a after spatial
      learning on 8-arm and 12-arm radial mazes.
AB  - The expression of Arc and Homer 1a (H1a) depends on neural activity. This study
      was designed to determine hippocampal Arc and H1a mRNA expression levels after
      spatial learning with differing behavioral task demands. Forty-four male rats
      were distributed into 11 groups of four. One group received no training or trial
      sessions. Of the ten remaining groups, three were tested on the 8-arm maze, three
      on the 12-arm maze, two on the 8-arm maze and then the 12-arm maze, and two on
      the 12-arm maze and then the 8-arm maze. Each animal was sacrificed 30 min after
      the last session of maze testing and its hippocampus was immediately dissected
      and stored at -80 degrees C. The level of mRNA expression at different stages of
      maze learning was determined using real-time reverse-transcription polymerase
      chain reaction (qRT-PCR). Significantly elevated expression of both Arc and H1a
      was observed. The orchestrated expression levels of both genes were correlated
      with the behavioral task demand level and behavioral performance.

PMID- 22617702
TI  - Metabotropic glutamate subtype 7 and 8 receptors oppositely modulate cardiac
      nociception in the rat nucleus tractus solitarius.
AB  - Recent study from our laboratory has indicated that microinjection of glutamate
      into the nucleus tractus solitarius (NTS) facilitates the cardiac-somatic reflex
      induced by pericardial capsaicin. Further, N-methyl-d-aspartate (NMDA) receptors
      and metabotropic glutamate receptors (mGluRs) mediate this function. However, the
      roles of the individual receptor subtypes or subunits in modulating cardiac
      nociception are unknown. Among the three groups of mGluRs, group III mGluRs are
      the primary mGluR subtype expressed in visceral afferent neurons in the NTS. The
      present study examined the roles of group III mGluRs and their subtype 7 and 8
      receptors (mGluR7 and mGluR8) in modulating the cardiac-somatic reflex induced by
      pericardial capsaicin, which was monitored by recording electromyogram (EMG)
      activity from the spinotrapezius muscle in anesthetized rats. Intra-NTS
      microinjection of a group III mGluR agonist, l-(+)-2-Amino-4-phosphonobutyric
      acid (l-AP4, at 1, 10, and 20 nmol) or a selective mGluR7 agonist, N,N'
      diphenylmethyl-1,2-ethanediamine dihydrochloride (AMN082, at 1, 2, and 4 nmol)
      both decreased the EMG response in a dose-dependent manner. This decrease was
      inhibited by the group III mGluR antagonist (RS)-alpha-Methylserine-O-phosphate
      (MSOP, at 20 nmol). In contrast, intra-NTS microinjection of a selective mGluR8
      agonist, (S)-3, 4-dicarboxyphenylglycine (DCPG, at 6 and 8 nmol), significantly
      increased the EMG response above control levels. This effect was eliminated by
      intra-NTS MSOP and by vagal deafferentation. These data suggest that group III
      mGluRs and mGluR7 in the NTS display an inhibitory effect, while mGluR8 displays
      a facilitatory effect in modulating cardiac nociception, and this facilitatory
      effect is dependent on vagal afferents.

PMID- 22617703
TI  - Smoking and oral health in dentate adults aged 18-64.
AB  - This report shows that among dentate adults aged 18-64 there are differences in
      oral health status and oral health care utilization among current smokers, former
      smokers, and never smokers. Overall, current smokers had a poorer oral health
      status and more oral health problems than either former smokers or never smokers.
      Current smokers were also more likely to delay routine dental visits. When
      current smokers experienced a mouth or tooth problem, they were less likely to
      visit a dental health professional because they were unable to afford dental care
      than former smokers or never smokers. However, current smokers were more likely
      to think that their oral health problem was important. The evidence for an
      association between tobacco use and oral diseases has been clearly shown in every
      Surgeon General's report on tobacco since 1964 (6). Tobacco use is a risk factor
      for oral cancers, periodontal diseases, and dental caries, among other diseases.
      Oral health problems may be early warning signs of other medical problems such as
      diabetes, HIV, heart disease, or stroke (6). Good oral health is integral to good
      general health.

PMID- 22617704
TI  - Synthesis of a glycopolymeric Pt(II) carrier and its induction of apoptosis in
      resistant cancer cells.
AB  - Post-polymerization modification of a poly(pentafluorostyryl) backbone with beta
      d-galactose and a terpyridine platinum complex yields a well-defined material
      that represents the first example of a metal-conjugated glycopolymer. It reveals
      anti-proliferative activity, no detectable necrotic cytotoxicity, and efficiently
      induces apoptosis in both wild-type as well as resistant Nalm-6 leukemia cell
      lines.

PMID- 22617705
TI  - A mechanistic appraisal of cognitive dysfunction in epilepsy.
AB  - A strong relationship between the clinical characteristics of epilepsy and the
      nature of cognitive impairments associated with the condition has been found, but
      the nature of this relationship appears to be quite complex and not well
      understood. This review presents a summary of the research on the interaction
      between cognition and epilepsy, surveyed from a mechanistic perspective with the
      aim of clarifying factors that contribute to the co-existence of both disorders.
      The physiological basis underpinning cognitive processing is first reviewed. The
      physiology of epilepsy is reviewed, with emphasis placed on interictal discharges
      and seizures. The nature of the impact of epilepsy on cognition is described,
      with transient and prolonged effects distinguished. Finally, the complexity of
      the co-morbidity between cognitive dysfunction and epilepsy is discussed in
      relation to childhood and adult-onset epilepsy syndromes and severe epileptic
      encephalopathies. Structural and functional abnormalities exist in patients with
      epilepsy that may underpin both the cognitive dysfunction and epilepsy,
      highlighting the complexity of the association. Research, possibly of a
      longitudinal nature, is needed to elucidate this multifactorial relationship
      between cognitive dysfunction and epilepsy.

PMID- 22617706
TI  - Blood modulates the kinetics of reactive oxygen release in pancreatic ischemia
      reperfusion injury.
AB  - OBJECTIVES: Reason for the unsuccessful use of antioxidants in transplantation
      might be the unknown kinetics of reactive oxygen species (ROS) release. In this
      study, we compared the kinetics of ROS release from rat pancreata in the presence
      and absence of blood. METHODS: In vivo, ischemia-reperfusion injury (IRI) was
      induced in pancreata of male Wistar rats by occlusion of the arterial blood
      supply for 1 or 2 hours. In vitro, isolated pancreata were single-pass perfused
      with Krebs-Henseleit bicarbonate solution. Reactive oxygen species were
      quantified by electron spin resonance spectroscopy using CMH (1-hydroxy-3
      methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine) as spin label. Thiols
      (glutathione), nicotinamide adenine dinucleotide phosphate-oxidase activity,
      myeloperoxidase activity, and adenosine triphosphate content were measured.
      RESULTS: During reperfusion, an increase in IRI-induced ROS in arterial blood was
      noted after 2 hours of warm ischemia. In sharp contrast, ROS release was
      immediate and short lived in blood-free perfused organs. The degree of tissue
      damage correlated with nicotinamide adenine dinucleotide phosphate-oxidase
      activity and adenosine triphosphate content. Antioxidative capacity of tissues
      was reduced. CONCLUSIONS: Electron spin resonance spectroscopy in conjunction
      with spin labels allows for the detection of ROS kinetics in pancreatic IRI.
      Reactive oxygen species kinetics are dependent on the length of the ischemic
      period and the presence or absence of blood.

PMID- 22617707
TI  - Intercellular adhesion molecule-1 blockade attenuates inflammatory response and
      improves microvascular perfusion in rat pancreas grafts.
AB  - OBJECTIVES: After pancreas transplantation (PTx), early capillary malperfusion
      and leukocyte recruitment indicate the manifestation of severe
      ischemia/reperfusion injury (IRI). Oscillatory blood-flow redistribution
      (intermittent capillary perfusion, IP), leading to an overall decrease in
      erythrocyte flux, precedes complete microvascular perfusion failure with
      persistent blood flow cessation. We addressed the role of intercellular adhesion
      molecule-1 (ICAM-1) for leukocyte-endothelial interactions (LEIs) after PTx and
      evaluated the contribution of IP and malperfusion. METHODS: Pancreas
      transplantation was performed in rats after 18-hour preservation, receiving
      either isotype-matched IgG or monoclonal anti-ICAM-1 antibodies (10 mg/kg
      intravenously) once before reperfusion. Leukocyte-endothelial interaction, IP,
      erythrocyte flux, and functional capillary density, respectively, were examined
      in vivo during 2-hour reperfusion. Nontransplanted animals served as controls.
      Tissue samples were analyzed by histomorphometry. RESULTS: In grafts of IgG
      treated animals, IP was encountered already at an early stage after reperfusion
      and steadily increased over 2 hours, whereas erythrocyte flux declined
      continuously. In contrast, inhibition of ICAM-1 significantly improved
      erythrocyte flux and delayed IP appearance by 2 hours. Further, anti-ICAM-1
      significantly reduced LEI and leukocyte tissue infiltration when compared to IgG;
      edema development was less pronounced in response to anti-ICAM-1 monoclonal
      antibody. CONCLUSION: Intercellular adhesion molecule-1 blockade significantly
      attenuates IRI via immediate reduction of LEI and concomitant improvement of
      capillary perfusion patterns, emphasizing its central role during IRI in PTx.

PMID- 22617708
TI  - Triptolide cooperates with Cisplatin to induce apoptosis in gemcitabine-resistant
      pancreatic cancer.
AB  - OBJECTIVES: We aim to pharmacologically downregulate heat shock protein 27
      (HSP27) through triptolide (TPL) to improve the drug sensitivity of pancreatic
      cancer to cisplatin (DDP). METHODS: In vitro, we assessed cell viability and
      apoptosis by the combination of TPL and DDP in gemcitabine-resistant human
      pancreatic carcinoma PANC-1 and MIA PaCa-2 cell lines and examined the effect of
      silencing HSP27 by a small interfering RNA on cytotoxicity induced by TPL or DDP.
      In vivo, we apply TPL with DDP in a xenograft model to test the synergic action.
      RESULTS: Triptolide cooperates with DDP to decrease cell viability and to induce
      apoptosis via the mitochondrial pathway, which is accompanied by a sharp decline
      in HSP27. Knocking down endogenous HSP27 can sensitize cancer cells to
      cytotoxicity with TPL or DDP, indicating the critical role of HSP27 down
      regulation in the synergic effect. Meanwhile, TPL acts in synergy with DDP to
      cause tumor regression in vivo. CONCLUSIONS: The combined therapy of TPL and DDP
      triggers a synergic apoptosis via inhibiting HSP27 in human gemcitabine-resistant
      pancreatic carcinoma and has a strong potential to be developed into a new
      effective regimen for pancreatic cancer treatment.

PMID- 22617709
TI  - Platelet activation in acute pancreatitis.
AB  - OBJECTIVES: The aim of this study was to assess the functional state of platelets
      in patients with mild acute pancreatitis and severe acute pancreatitis (S-AP).
      METHODS: The number of platelets and their morphological parameters were measured
      with Advia 2120. beta-Thromboglobulin and platelet factor 4 concentrations were
      determined by enzyme-linked immunosorbent assay method. To evaluate the
      expression of platelet glycoproteins, flow cytometry method was used. RESULTS: At
      the time of admission, a multiparameter evaluation of the platelets' function in
      AP patients showed enhanced platelet activation, which was reflected by an
      increase in the number of large platelets, concentration of degranulation markers
      (platelet factor 4 and beta-thromboglobulin), expression of glycoprotein (Gp)
      IIb/IIIa, and decreased mean platelet component. Only in S-AP patients at day 1 a
      decreased number of platelets and high expression of P-selectin and GpIa were
      observed, which may suggest their prognostic value. At day 30, the procoagulation
      state was still present in S-AP patients, because of increased platelets and
      number of large platelets as well as high GpIIb/IIIa expression. CONCLUSIONS:
      These results may indicate an important role of platelet activation in the
      pathogenesis of acute pancreatitis and the development of complications in S-AP.

PMID- 22617710
TI  - Blood flow in endogenous and transplanted pancreatic islets in anesthetized rats:
      effects of lactate and pyruvate.
AB  - OBJECTIVE: The objective of this study was to evaluate the effects of exogenously
      administered lactate and pyruvate on blood perfusion in endogenous and
      transplanted islets. METHODS: Anesthetized Wistar-Furth rats were given lactate
      or pyruvate intravenously, and regional blood perfusion was studied 3 or 30
      minutes later with a microsphere technique. Separate rats received a 30-minute
      infusion of pyruvate or lactate into the portal vein before blood flow
      measurements. We also administered these substances to islet-implanted rats 4
      weeks after transplantation and measured graft blood flow with laser Doppler
      flowmetry. The expression of monocarboxylate transporter 1 and lactate
      dehydrogenase A was analyzed. RESULTS: The expression of monocarboxylate
      transporter 1 and lactate dehydrogenase A was markedly up-regulated in
      transplanted as compared with endogenous islets. Administration of pyruvate, but
      not lactate, increased mesenteric blood flow after 3 minutes. Pyruvate decreased
      mesenteric blood flow after 30 minutes, whereas lactate decreased only islet
      blood flow. These responses were absent in transplanted animals. A continuous
      intraportal infusion of lactate or pyruvate increased selectively islet blood
      flow but did not affect blood perfusion of transplanted islets. CONCLUSIONS:
      Lactate and pyruvate affect islet blood flow through effects mediated by
      interactions between the liver and the nervous system. Such a response can help
      adjust the release of islet hormones during excess substrate concentrations.

PMID- 22617712
TI  - Risk factors for hepatic steatosis after pancreatectomy: a retrospective
      observational cohort study of the importance of nutritional management.
AB  - OBJECTIVES: The occurrence of hepatic steatosis after pancreatectomy has been
      previously known. However, this condition has been neglected because its clinical
      course has been considered benign. The aims of this study were to identify the
      risk factors for hepatic steatosis after pancreatectomy, to clarify the impact of
      this condition on long-term prognosis, and to suggest methods for preventing
      hepatic steatosis. METHODS: One hundred two patients, who were diagnosed with
      postoperative computed tomography, were enrolled. The severity of hepatic
      steatosis was determined by using unenhanced computed tomography. The variables
      that might influence the development of hepatic steatosis were compared between
      the groups with and without hepatic steatosis. RESULTS: The incidence of
      postoperative hepatic steatosis was 31.4%. Multivariate analysis showed that
      absence of postoperative insulin use (P < 0.01) and decrease in postoperative
      body mass index of greater than 3 kg/m(2) (P < 0.01) were independent risk
      factors for hepatic steatosis. The cumulative recurrence-free survival rate of
      the group with hepatic steatosis was poorer than that of the group without (P =
      0.053). CONCLUSIONS: Postoperative hepatic steatosis may affect long-term
      prognosis after pancreatectomy. Surgeons should take care of nutritional
      management including insulin therapy for patients with hepatic steatosis after
      pancreatectomy.

PMID- 22617713
TI  - Nationwide improvement of only short-term survival after resection for pancreatic
      cancer in the Netherlands.
AB  - OBJECTIVES: Evaluation of incidence, treatment, and survival trends after
      resection of pancreatic cancer at a national level. METHODS: Using data on
      patient and tumor characteristics from the nationwide Netherlands Cancer Registry
      trends were analyzed for the period 1989-2008. RESULTS: A total of 30,025
      patients diagnosed with pancreatic cancer were included. The incidence remained
      stable over the 20-year study period at approximately 9 per 100,000 inhabitants.
      Resection rates increased from 8% in 1989 to 12% in 2008, adjuvant chemotherapy
      rates increased from 7% to 29%, and palliative chemotherapy rates increased from
      5% to 19% (P < 0.0001 each). Relative survival proportions did not change over
      time; besides a minimal, nonsignificant increase at 3 months from 53% to 55%,
      these remained 34% at 6 months and 4.5% at 3 years. Among the patients undergoing
      tumor resection, relative survival increased from 82% to 93% at 3 months and from
      51% to 63% at 1 year after diagnosis. However, no improvement was seen after 3
      years (23%). CONCLUSIONS: The increased short-term survival among patients who
      underwent resection probably reflects decreased postoperative mortality driven by
      ongoing centralization efforts. However, longer-term survival remained poor
      irrespective of the changes in management in the past decades.

PMID- 22617711
TI  - Ethanol administration impairs pancreatic repair after injury.
AB  - OBJECTIVES: Alcohol abuse is one of the most common factors associated with acute
      and chronic pancreatitis. Although it is evident that alcohol abuse can have an
      important role in the development of pancreatitis, it does not seem that alcohol
      abuse alone is responsible for this disease. We investigated the involvement of
      ethanol in the impairment of pancreatic repair after induction of pancreatitis.
      METHODS: A biologically relevant mouse model of alcoholic pancreatitis, combining
      long-term ethanol consumption and coxsackievirus infection, was used to
      investigate the effects of ethanol on pancreatic regeneration. Tissues were
      harvested and analyzed by reverse transcription-polymerase chain reaction and
      immunoblot. RESULTS: These studies demonstrate that long-term ethanol consumption
      impairs the structural repair of the exocrine pancreas. This is accompanied by a
      delay in the restitution of lipase expression. In addition, impaired expression
      of the critical pancreatic transcription factors, PDX1 and PTF1, and the mediator
      of Notch signaling, HES1, was observed. CONCLUSIONS: Long-term ethanol
      consumption impairs the structural repair and functional restitution of the
      pancreas after severe injury. These impairments may, in part, be explained by the
      impaired expression of factors important in the development and maintenance of
      the exocrine pancreas. Impaired pancreatic regeneration may have a role in the
      pathogenesis of alcoholic pancreatitis.

PMID- 22617714
TI  - Serum levels of adipocyte fatty acid-binding protein are decreased in chronic
      pancreatitis.
AB  - OBJECTIVE: Chronic pancreatitis (CP) is associated with an increased risk for
      diabetes mellitus and vascular disease. Adipocyte fatty acid-binding protein
      (AFABP) is a novel adipokine that is independently associated with the metabolic
      syndrome and cardiovascular disease. In the current study, we investigated serum
      AFABP levels in CP patients compared with sex- and body mass index-matched
      controls. METHODS: Adipocyte fatty acid-binding protein was determined with
      enzyme-linked immunosorbent assay in control subjects (n = 60) and diabetic as
      well as nondiabetic CP (n = 60) patients and correlated to clinical and
      biochemical measures of glucose and lipid metabolism, as well as renal function
      in both groups. RESULTS: Median serum AFABP levels were significantly lower in CP
      patients compared with controls (12.5 vs 20.9 MUg/L, P = 0.003). Furthermore,
      body mass index, sex, and CP independently predicted circulating AFABP. In
      contrast, no significant difference in circulating AFABP could be demonstrated
      between diabetic and nondiabetic CP patients. CONCLUSIONS: Circulating AFABP is
      paradoxically lower in CP patients and does not depend on pancreatic diabetes.
      Our data do not support a role of circulating AFABP in metabolic and vascular
      risk in CP patients.

PMID- 22617715
TI  - Clinical value of circulating lipocalins and insulin-like growth factor axis in
      pancreatic cancer diagnosis.
AB  - OBJECTIVES: Early diagnosis of pancreatic cancer (PC) in diabetic patients is
      difficult owing to late presentation of symptoms. Hence, finding a marker to
      identify cancer stage early would be useful to improve survival. We aimed to
      determine levels of serum retinol binding protein 4 (RBP-4), neutrophil
      gelatinase-associated lipocalin (NGAL), insulin-like growth factor I (IGF-I), and
      its binding protein 3 (IGFBP-3) in patients with PC with preexisting type 2
      diabetes. Moreover, we assessed their clinical usefulness in PC diagnosis and
      their association with tumor severity. METHODS: Twenty-three patients with PC, 32
      diabetic patients, and 20 healthy controls were examined. Preoperative and
      postoperative samples were obtained from 15 patients with PC. Serum insulin,
      cancer antigen (CA 19-9), RBP-4, NGAL, IGF-I, and IGFBP-3 levels were estimated
      by enzyme-linked immunosorbent assay. RESULTS: Significant elevation in the
      levels of RBP-4 (60.1 [46.3-71.4] ng/mL), NGAL (142 [80-235] ng/mL), and IGF-I
      (174 [9.3] ng/mL) together with significant reduction in the level of IGFBP-3
      (3669 [299] ng/mL) was found in patients with PC. Moreover, RBP-4 and NGAL levels
      were reduced in postoperative samples compared with preoperative ones. Receiver
      operating characteristic curve analysis revealed that they can distinguish PC
      from non-PC cases with significant area under the curve. CONCLUSIONS: Retinol
      binding protein 4, NGAL, IGF-I, and IGFBP-3 are associated with PC in type 2
      diabetic patients. They could be useful in distinguishing PC from non-PC cases
      when used in combination or with cancer antigen.

PMID- 22617716
TI  - Comparative evaluation of the teratogenicity of genistein and genistin using rat
      whole embryo culture and limbud micromass culture methods.
AB  - Genistein (GEN) is one kind of phytoestrogen. Several studies have demonstrated
      the teratogenic potential of GEN in vitro by postimplantation rat whole embryo
      culture (WEC) assay, but GEN showed no teratogenic effects in vivo even at a dose
      up to 1000 mg/kg bw/day. The mechanism of such discrepancy is still unclear.
      Because more than 80% of total genistein (free plus glycoside form) in
      circulation is its glycoside metabolite, genistin (GIN), we thus hypothesize that
      genistin is non-teratogenic. To prove this hypothesis, rat whole embryo culture
      (WEC) and limbud micromass culture methods were applied to compare the
      teratogenic effects of GEN and GIN on developing embryos in vitro. In WEC assay,
      we found that the development of embryos was affected by GEN treatment dose
      dependently, while GIN-treated embryos displayed slight developmental defects
      only at the highest dose (222 MUM). In micromass culture assay, the IC50 of cell
      proliferation and differentiation for GEN were 15.6 and 37.2 MUM, respectively,
      while neither was influenced by GIN treatment up to 111 MUM. Collectively, our
      study indicated that GEN showed no teratogenic effects in vivo probably due to
      its transformation to the non-teratogenic metabolite, GIN.

PMID- 22617717
TI  - Daily intake of inorganic arsenic and some organic arsenic species of Japanese
      subjects.
AB  - The daily dietary intake of inorganic arsenic (InAs) and some of organic arsenic
      (OrAs) species of Japanese subjects were estimated by determining the
      concentrations of As species in two different sets of total diet sample:
      duplicated diet samples collected from 25 subjects in Japan and a certified
      reference material with total diet matrix (NIES CRM No. 27 Typical Japanese Diet,
      TJD). The concentration of InAs and OrAs in diet samples were determined by LC
      ICP-MS using a photo-oxidation and hydride generation system. The median intake
      of InAs for the 25 subjects was 3.8 MUg day(-1) (2.0-57 MUg day(-1)) and intake
      of 27 MUg day(-1) was estimated from TJD. The median intake of MMA, DMA and TMAsO
      were <0.18, 1.1 and <0.053 MUg day(-1) for the 25 subjects and that of MMA, DMA,
      AB and TMAsO was estimated to be 3.9, 11, 140 and 5.9 MUg day(-1), respectively,
      based on TJD analysis. On the basis of InAs intakes estimated and the oral slope
      factor of the US EPA and Health Canada, excess cancer risk was estimated to
      exceed acceptable level. Cancer risk posed by the dietary InAs of the general
      Japanese may not be negligible.

PMID- 22617718
TI  - Association of cigarette smoking and CRP levels with DNA methylation in alpha-1
      antitrypsin deficiency.
AB  - Alpha-1 antitrypsin (AAT) deficiency and tobacco smoking are confirmed risk
      factors for Chronic Obstructive Pulmonary Disease. We hypothesized that variable
      DNA methylation would be associated with smoking and inflammation, as reflected
      by the level of C-Reactive Protein (CRP) in AAT-deficient subjects. Methylation
      levels of 1,411 autosomal CpG sites from the Illumina GoldenGate Methylation
      Cancer Panel I were analyzed in 316 subjects. Associations of five smoking
      behaviors and CRP levels with individual CpG sites and average methylation levels
      were assessed using non-parametric testing, linear regression and linear mixed
      effect models, with and without adjustment for age and gender. Univariate linear
      regression analysis revealed that methylation levels of 16 CpG sites
      significantly associated with ever-smoking status. A CpG site in the TGFBI gene
      was the only site associated with ever-smoking after adjustment for age and
      gender. No highly significant associations existed between age at smoking
      initiation, pack-years smoked, duration of smoking, and time since quitting
      smoking as predictors of individual CpG site methylation levels. However, ever
      smoking and younger age at smoking initiation associated with lower methylation
      level averaged across all sites. DNA methylation at CpG sites in the RUNX3, JAK3
      and KRT1 genes associated with CRP levels. The most significantly associated CpG
      sites with gender and age mapped to the CASP6 and FZD9 genes, respectively. In
      summary, this study identified multiple potential candidate CpG sites associated
      with ever-smoking and CRP level in AAT-deficient subjects. Phenotypic variability
      in Mendelian diseases may be due to epigenetic factors.

PMID- 22617719
TI  - Bisphenol A in 24 h urine and plasma samples of the German Environmental Specimen
      Bank from 1995 to 2009: a retrospective exposure evaluation.
AB  - Human exposure to Bisphenol A (BPA) is omnipresent. Both the extent of the
      exposure and its toxicological relevance are controversially discussed. We aim to
      reliably determine and evaluate the extent of BPA body burden in the German
      population from 1995 to 2009 based on 600 24 h urine samples and corresponding
      plasma samples from the Environmental Specimen Bank. We determined total and
      unconjugated BPA in urine and plasma using on-line solid-phase extraction high
      performance liquid chromatography coupled to isotope dilution tandem mass
      spectrometry with a limit of quantification (LOQ) of 0.1 MUg/l. In the stored
      urines, total BPA was quantifiable in >96% (median: 1.49 MUg/l; 95th percentile:
      7.37 MUg/l), whereas unconjugated BPA was quantifiable only in <15% of the
      samples. Total BPA concentrations decreased over time, but 24 h urine volumes
      increased. Therefore, daily intakes calculated from the 24 h urines remained
      rather constant at a median of 0.037 and a 95th percentile of 0.171 MUg BPA/kg
      body weight/day. In 60 corresponding plasma samples, total BPA levels were
      generally below the LOQ of 0.1 MUg/l and, if quantifiable, most BPA was
      unconjugated, thus hinting to external contamination. We see total BPA in urine
      as the most appropriate and robust marker for BPA exposure assessment (if
      controlled for BPA contamination). Unconjugated BPA in urine and unconjugated or
      total BPA in plasma where contamination or breakdown of the glucuronide cannot be
      ruled out are of no value for human exposure assessment.

PMID- 22617720
TI  - Prevalence of dampness and mold in European housing stock.
AB  - An assessment of the prevalence of dampness and mold in European housing stock
      was carried out. It is based on general indicators of dampness and mold in
      dwellings reported in the literature. The assessment relies on recent studies,
      taking into account regional and climatic differences, as well as differences in
      study design, methodology, and definitions. Data were available from 31 European
      countries. Weighted prevalence estimates are 12.1% for damp, 10.3% for mold,
      10.0% for water damage, and 16.5% for a combination of any one or more
      indicators. Significant (up to 18%) differences were observed for dampness and
      mold prevalence estimates depending on survey factors, region, and climate. In
      conclusion, dampness and/or mold problems could be expected to occur in one of
      every six of the dwellings in Europe. Prevalence and occurrence of different
      types of problems may vary across geographical areas, which can be partly
      explained by differences in climate.

PMID- 22617721
TI  - Elevated blood lead levels and sources of exposure in the population of Kinshasa,
      the capital of the Democratic Republic of Congo.
AB  - The objective of this study was to determine blood lead levels (BLLs) and the
      possible sources of exposure in the population of Kinshasa, the capital of the
      Democratic Republic of Congo. A cross-sectional survey was carried out from
      January to May 2008 in a representative sample of the Kinshasan population. BLL
      was measured in 275 individuals (53.4% women) aged 1-70 years in the urban area
      of Kinshasa and from 60 additional subjects in the rural area. Pb was also
      determined in environmental specimens (air and soil, indoor and outdoor). BLL in
      the study population ranged from 2.9 to 49.3 MUg/dl (median, 9.9 MUg/dl). The
      median BLL among children aged <6 years was 11.5 MUg/dl (range: 3.0-37.8 MUg/dl).
      Of these children, 71% had elevated BLL (>=10 MUg/dl) and 22% had BLL >=20
      MUg/dl. The proportion of elevated BLL (>=10 MUg/dl) was higher for children aged
      <3 years than for children aged 3 to 5 years (97% vs 56%). A higher prevalence of
      elevated BLL was observed in urban compared with rural children (71% vs 20%).
      Significantly higher BLLs were also found in children whose mother consumed fired
      clay during pregnancy. Residential informal activities in the recycling of car
      batteries also contributed to elevated BLL in children. The elevated background
      of Pb exposure in the Kinshasan population indicates a public health issue that
      requires corrective actions. Pb-contaminated dust and air in children's home is
      an issue of public health concern. The use of leaded gasoline and the activities
      of car battery recycling in certain residences appear to constitute the main
      sources of exposure in the city of Kinshasa. The traditional use of fired clay
      for the treatment of gastritis by pregnant women is another significant
      contributor for elevated BLL in children.

PMID- 22617722
TI  - Variability in the fraction of ambient fine particulate matter found indoors and
      observed heterogeneity in health effect estimates.
AB  - Exposure to ambient (outdoor-generated) fine particulate matter (PM(2.5)) occurs
      predominantly indoors. The variable efficiency with which ambient PM(2.5)
      penetrates and persists indoors is a source of exposure error in air pollution
      epidemiology and could contribute to observed temporal and spatial heterogeneity
      in health effect estimates. We used a mass balance approach to model F for
      several scenarios across which heterogeneity in effect estimates has been
      observed: with geographic location of residence, residential roadway proximity,
      socioeconomic status, and central air-conditioning use. We found F is higher in
      close proximity to primary combustion sources (e.g. proximity to traffic) and for
      lower income homes. F is lower when PM(2.5) is enriched in nitrate and with
      central air-conditioning use. As a result, exposure error resulting from
      variability in F will be greatest when these factors have high temporal and/or
      spatial variability. The circumstances for which F is lower in our calculations
      correspond to circumstances for which lower effect estimates have been observed
      in epidemiological studies and higher F values correspond to higher effect
      estimates. Our results suggest that variability in exposure misclassification
      resulting from variability in F is a possible contributor to heterogeneity in PM
      mediated health effect estimates.

PMID- 22617724
TI  - Unifying the criteria of elastic stability of solids.
AB  - The elastic stability criterion formulated by Born is based on the convexity
      requirement of the equilibrium free energy F of a stress-free crystal under small
      strain fluctuation, that demands the elastic constant tensor C to be positive
      definite, |C| > 0. For a crystal subject to an external stress, Hill specifies
      that for the crystal to be stable, the difference between its internal energy
      change deltaE and the work done to the system deltaW must be positive, i.e.
      deltaE - deltaW > 0. Polanyi, Frenkel, and Orowan proposed a different stability
      criterion based on stress increment for a loaded system, tau(epsilon +
      Deltaepsilon) - tau(epsilon) > 0 until the limit is reached at dtau/depsilon = 0.
      Although known empirically, the formal connection between the different criteria
      has not been established rigorously. Using finite deformation theory, we show
      quite simply that the different formulations of the stability criteria originate
      from the same necessary condition for the convexity of the free energy of the
      system subject to external loading, f = F - W. However, in practice caution must
      be taken in implementation of the different criteria; they may lead to quite
      different results, especially when stability bifurcation occurs.

PMID- 22617723
TI  - Review of research on residential mobility during pregnancy: consequences for
      assessment of prenatal environmental exposures.
AB  - Studies on environmental exposures during pregnancy often have limited
      residential history (e.g., at delivery), potentially introducing exposure
      misclassification. We reviewed studies reporting residential mobility during
      pregnancy to summarize current evidence and discuss research implications. A
      meaningful quantitative combination of results (e.g., meta-analysis), was
      infeasible owing to variation in study designs. Fourteen studies were identified,
      of which half were from the US. Most were case-control studies examining birth
      defects. Residential history was typically assessed after delivery. Overall
      mobility rates were 9-32% and highest in the second trimester. Mobility generally
      declined with age, parity, and socioeconomic status, although not consistently.
      Married mothers moved less frequently. Findings were dissimilar by race, smoking,
      or alcohol use. On the basis of the few studies reporting distance moved, most
      distances were short (median often <10 km). Results indicate potential
      misclassification for environmental exposures estimated with incomplete
      residential information. This misclassification could be associated with
      potential confounders, such as socioeconomics, thereby affecting risk estimates.
      As most moves were short distances, exposures that are homogenous within a
      community may be well estimated with limited residential data. Future research
      should consider the implications of residential mobility during pregnancy in
      relation to the exposure's spatial heterogeneity and factors associated with the
      likelihood of moving and distance moved.

PMID- 22617726
TI  - Response to Commentary on 'The wonders of new available post-analysis CT software
      in the hands of vascular surgeons'.

PMID- 22617725
TI  - The Anopheles gambiae cE5, a tight- and fast-binding thrombin inhibitor with post
      transcriptionally regulated salivary-restricted expression.
AB  - Mosquito saliva carries a large number of factors with anti-hemostatic, anti
      inflammatory and immuno-modulatory activities. The cE5 protein was initially
      identified during an Anopheles gambiae salivary gland transcriptome study and
      later shown to share sequence similarity with anophelin, a thrombin inhibitor
      from the saliva of the New World mosquito Anopheles albimanus. The cE5 gene was
      found to encode different mRNA isoforms coexisting in several tissues of both
      male and female mosquitoes, a highly unusual profile for a gene potentially
      encoding an anti-thrombin and involved in blood feeding. Expression of the cE5
      protein and assessment of its activity and inhibitory properties showed that it
      is a highly specific and tight-binding thrombin inhibitor, which differs from the
      A. albimanus orthologue for the fast-binding kinetics. Despite the widespread
      occurrence of cE5 transcripts in different mosquito tissues the corresponding
      protein was only found in female salivary glands, where it undergoes post
      translational modification. Therefore, tissue-specific restriction of the A.
      gambiae cE5 is not achieved by transcriptional control, as common for mosquito
      salivary genes involved in hematophagy, but by post-trascriptional gene
      regulatory mechanisms. Our observations provide a paradigm of post
      transcriptional regulation as key determinant of tissue specificity for a protein
      from an important disease vector and point out that transcriptomic data should be
      interpreted with caution in the absence of concomitant proteomic support.

PMID- 22617728
TI  - Commentary on 'simvastatin decreases free radicals formation in the human
      abdominal aortic aneurysm wall via NF-kappaB'.

PMID- 22617729
TI  - Commentary on 'A systematic review of the role of cardio-pulmonary exercise
      testing in vascular surgery'.

PMID- 22617730
TI  - Commentary on 'Multi-center experience of 164 consecutive Hemodialysis Reliable
      Outflow graft implants for hemodialysis treatment'.

PMID- 22617731
TI  - Management and outcome of prosthetic patch infection after carotid
      endarterectomy: a single-centre series and systematic review of the literature.
AB  - OBJECTIVES: Outcomes following prosthetic patch infection after carotid
      endarterectomy (CEA). METHODS: Retrospective audit and systematic review.
      RESULTS: 22 patients were treated between January 1992 and April 2012, 5 having
      undergone their original CEA at another institution. The commonest infecting
      organism was Staphylococcus. One patient was treated by antibiotic irrigation,
      one was stented, while 20 underwent debridement and patch excision plus; carotid
      ligation (n = 3), vein patching (n = 3) or vein bypass (n = 14). There was one
      peri-operative stroke, but no peri-operative deaths. There were no reinfections
      at a median follow-up of 54 months. A systematic review identified 123 patients
      with prosthetic patch infection in the world literature. Thirty-six (29%)
      presented <2 months, 78 (63%) presented >6 months after the original CEA. Seventy
      nine of/87 patients (91%) with a positive culture yielded Staphylococci or
      Streptococci. Seventy-four patients were treated by patch excision and autologous
      reconstruction. Four (5%) developed reinfection <30 days, but later reinfections
      have been reported. Seven of nine patients (78%) undergoing prosthetic
      reconstruction either died or suffered reinfection. Five patients were treated
      with a covered stent, none developing reinfection (median followup 12 months).
      CONCLUSION: Patch infection following CEA is rare. Few have undergone stenting
      and long term data are awaited. For now, patch excision and autologous
      reconstruction remains the 'gold standard'.

PMID- 22617732
TI  - Carotid stenosis: an unknown disease...

PMID- 22617733
TI  - Cost effectiveness of peer support for type 2 diabetes.
AB  - OBJECTIVES: The aim of this study is to examine the cost-effectiveness of a group
      based peer support intervention in general practice for patients with type 2
      diabetes. METHODS: Incremental cost utility analysis combining within trial and
      beyond trial components to compare the lifetime costs and benefits of alternative
      strategies: CONTROL: standardized diabetes care; INTERVENTION: group-based peer
      support in addition to standardized diabetes care. Within trial analysis was
      based on a cluster randomized controlled trial of 395 patients with type 2
      diabetes in the east of Ireland. Beyond trial analysis was conducted using the
      United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model. Uncertainty was
      explored using a range of sensitivity analyses and cost-effectiveness
      acceptability curves were generated. RESULTS: Compared with the control strategy,
      the intervention was associated with an increase of 0.09 (95 percent confidence
      interval [CI], -0.05 to 0.25) in mean quality-adjusted life-years per patient and
      savings of ?637.43 (95 percent CI, -2455.19 to 1125.45) in mean healthcare cost
      per patient and ?623.39 (95 percent CI, -2507.98 to 1298.49) in mean total cost
      per patient respectively. The likelihood of the intervention being cost-effective
      was appreciably higher than 80 percent for a range of potential willingness-to
      pay cost-effectiveness thresholds. CONCLUSIONS: Our results suggest that while a
      group-based peer support intervention shows a trend toward improved risk factor
      management, we found no significant differences in final cost or effectiveness
      endpoints between intervention and control. The probabilistic results suggest
      that the intervention was more cost-effective, with probability values of higher
      than 80 percent across a range of potential cost-effectiveness threshold values.

PMID- 22617734
TI  - Incidence-based cost-of-illness model for metastatic breast cancer in the United
      States.
AB  - OBJECTIVES: This study aims to estimate the annual U.S. societal costs associated
      with treatment of metastatic breast cancer (MBC) patients using an incidence
      based cost-of-illness (COI) framework. METHODS: An incidence-based COI model was
      constructed in which MBC patients were simulated from diagnosis through active
      treatment, palliative care, and death over 5 years. Key model parameters
      included: annual incidence of breast cancer in the metastatic stage, utilization
      of cancer therapies and other medical care resources, treatment-related adverse
      events, unit costs, work days missed by patient and caregiver, and wage rates.
      Overall survival was based on SEER data and costs were assigned to living
      patients monthly, according to their disease management phase. The outcomes
      measures were total discounted societal costs, cost/year, and cost/patient-year.
      RESULTS: The annual incidence of MBC in the United States in 2007 was estimated
      to be 49,674 patients (de novo and progressed from earlier stages). The total
      discounted cost to society attributable to MBC was $12.2 billion for the incident
      cohort, or $98,571 per patient-year. The 5-year direct medical cost of this
      incident cohort was $9.3 billion, or $75,415 per patient-year. Treatment-related
      costs (active treatment, toxicity management, and medical follow-up) contributed
      44 percent of MBC expenditure, followed by palliative/best supportive care costs
      (31 percent). Lost productivity accounted for approximately 21 percent of the
      total cost ($2.6 billion over 5 years or $21,153 per patient-year). CONCLUSIONS:
      The societal burden of MBC in the United States is substantial. Earlier detection
      and effective treatment could lead to a significant decrease in costs while
      improving overall disease prognosis.

PMID- 22617735
TI  - Effectiveness and cost-effectiveness of supplemental glutamine dipeptide in total
      parenteral nutrition therapy for critically ill patients: a discrete event
      simulation model based on Italian data.
AB  - INTRODUCTION: The supplementation of alanyl-glutamine dipeptide in critically ill
      patients necessitating total parenteral nutrition (TPN) improves clinical
      outcomes, reducing mortality, infection rate, and shortening intensive care unit
      (ICU) hospital lengths of stay (LOSs), as compared to standard TPN regimens.
      METHODS: A Discrete Event Simulation model that incorporates outcomes rates from
      200 Italian ICUs for over 60,000 patients, alanyl-glutamine dipeptide efficacy
      data synthesized by means of a Bayesian random effects meta-analysis, and
      national cost data has been developed to evaluate the alternatives from the cost
      perspective of the hospital. Simulated clinical outcomes are death and infection
      rates in ICU, death rate in general ward, and hospital LOSs. Sensitivity analyses
      are performed by varying all uncertain parameter values in a plausible range.
      RESULTS: The internal validation process confirmed the accuracy of the model in
      replicating observed clinical data. Alanyl-glutamine dipeptide on average results
      more effective and less costly than standard TPN: reduced mortality rate (24.6%
      +/- 1.6% vs. 34.5% +/- 2.1%), infection rate (13.8% +/- 2.9% vs. 18.8% +/- 3.9%),
      and hospital LOS (24.9 +/- 0.3 vs. 26.0 +/- 0.3 days) come at a lower total cost
      per patient (23,409 +/- 3,345 vs. 24,161 +/- 3,523 Euro).Treatment cost is
      completely offset by savings on ICU and antibiotic costs. Sensitivity analyses
      confirmed the robustness of these results. CONCLUSIONS: Alanyl-glutamine
      dipeptide is expected to improve clinical outcomes and to do so with a concurrent
      saving for the Italian hospital.

PMID- 22617736
TI  - A model for assessment of telemedicine applications: mast.
AB  - OBJECTIVES: Telemedicine applications could potentially solve many of the
      challenges faced by the healthcare sectors in Europe. However, a framework for
      assessment of these technologies is need by decision makers to assist them in
      choosing the most efficient and cost-effective technologies. Therefore in 2009
      the European Commission initiated the development of a framework for assessing
      telemedicine applications, based on the users' need for information for decision
      making. This article presents the Model for ASsessment of Telemedicine
      applications (MAST) developed in this study. METHODS: MAST was developed through
      workshops with users and stakeholders of telemedicine. RESULTS: Based on the
      workshops and using the EUnetHTA Core HTA Model as a starting point a three
      element model was developed, including: (i) preceding considerations, (ii)
      multidisciplinary assessment, and (iii) transferability assessment. In the
      multidisciplinary assessment, the outcomes of telemedicine applications comprise
      seven domains, based on the domains in the EUnetHTA model. CONCLUSIONS: MAST
      provides a structure for future assessment of telemedicine applications. MAST
      will be tested during 2010-13 in twenty studies of telemedicine applications in
      nine European countries in the EC project Renewing Health.

PMID- 22617737
TI  - A comparison of two search methods for determining the scope of systematic
      reviews and health technology assessments.
AB  - OBJECTIVES: This study aims to compare two different search methods for
      determining the scope of a requested systematic review or health technology
      assessment. The first method (called the Direct Search Method) included
      performing direct searches in the Cochrane Database of Systematic Reviews (CDSR),
      Database of Abstracts of Reviews of Effects (DARE) and the Health Technology
      Assessments (HTA). Using the comparison method (called the NHS Search Engine) we
      performed searches by means of the search engine of the British National Health
      Service, NHS Evidence. METHODS: We used an adapted cross-over design with a
      random allocation of fifty-five requests for systematic reviews. The main
      analyses were based on repeated measurements adjusted for the order in which the
      searches were conducted. RESULTS: The Direct Search Method generated on average
      fewer hits (48 percent [95 percent confidence interval {CI} 6 percent to 72
      percent], had a higher precision (0.22 [95 percent CI, 0.13 to 0.30]) and more
      unique hits than when searching by means of the NHS Search Engine (50 percent [95
      percent CI, 7 percent to 110 percent]). On the other hand, the Direct Search
      Method took longer (14.58 minutes [95 percent CI, 7.20 to 21.97]) and was
      perceived as somewhat less user-friendly than the NHS Search Engine (-0.60 [95
      percent CI, -1.11 to -0.09]). CONCLUSIONS: Although the Direct Search Method had
      some drawbacks such as being more time-consuming and less user-friendly, it
      generated more unique hits than the NHS Search Engine, retrieved on average fewer
      references and fewer irrelevant results.

PMID- 22617738
TI  - Brazilian health technology assessment bulletin: editorial process, dissemination
      strategies, critical appraisal, and initial impact.
AB  - OBJECTIVES: This study reports on the Brazilian experience of developing a
      specialized bulletin, the Brazilian Health Technology Assessment Bulletin
      (BRATS), on health technology assessments (HTA). METHODS: The editorial process,
      format, and dissemination strategy of the publication are presented. A critical
      appraisal of the available issues was made using the checklist for HTA reports of
      the International Network of Agencies for Health Technology Assessment. The
      initial impact was estimated based on a retrospective observational measurement
      of the types of publications that cite the bulletin as a source of information.
      The publications citing BRATS were identified using Google Scholar. RESULTS:
      Since June 2008, fourteen issues of the bulletin have been produced. BRATS has
      not presented any significant limitation that would compromise generalizations of
      its results within the Brazilian context. The initial impact of the bulletin,
      however, has been small, which may be due to its exclusively electronic
      dissemination format and technical language. We found nine publications citing
      BRATS in Google Scholar. CONCLUSIONS: It is hoped that the bulletin will promote
      the continuity of HTA actions among health-sector managers and professionals in
      Brazil.

PMID- 22617739
TI  - Health technology assessment in Poland and Scotland: comparison of process and
      decisions.
AB  - OBJECTIVES: We compared Polish and Scottish Health Technology Assessment (HTA)
      process in order to elicit recommendations for future development of HTA
      methodological guidelines in Poland. METHODS: We studied the differences between
      Polish and Scottish HTA methodological guidelines. HTA recommendations issued by
      Polish HTA agency (AHTAPol) in the period January 1 through December 31, 2008,
      were benchmarked to HTA guidance published by Scottish Medical Consortium (SMC)
      for the same drug technology. RESULTS: The Scottish HTA methodological guidelines
      were more instructive in terms of clinical and economic evaluations than Polish
      guidelines. SMC evaluated forty-eight of sixty-eight drug technologies appraised
      by AHTAPoL. There were thirty drug technologies that received similar guidance in
      both countries and eighteen with contradictory HTA recommendations. In Scotland,
      there were more positive HTA recommendations than there were in Poland. While
      comments about efficacy or safety were commonplace among reasons for negative
      recommendations in Poland, insufficient justification of treatment's cost in
      relation to benefits was the most often cited reason for rejection in Scotland.
      SMC tended to recommend restricted use to specific sub-populations for several
      drug technologies negatively appraised by AHTAPoL. CONCLUSIONS: The comparison
      between SMC and AHTAPoL suggests that there is potential room of improvement of
      the Polish HTA methodological guidelines. Comparative effectiveness and safety,
      subgroup analysis, and adaptation of models to local settings were identified as
      key areas for further development of Polish HTA methodological guidelines.

PMID- 22617740
TI  - Rapidly curable chitosan-PEG hydrogels as tissue adhesives for hemostasis and
      wound healing.
AB  - Chitosan-poly(ethylene glycol)-tyramine (CPT) hydrogels were rapidly formed in
      situ using horseradish peroxidase and hydrogen peroxide to explore their
      performance as efficient tissue adhesives. A poly(ethylene glycol) modified with
      tyramine was grafted onto a chitosan backbone to enhance the solubility of the
      chitosan and to crosslink into three-dimensional networks. The elastic modulus of
      the hydrogels could be controlled by changing the crosslinking conditions, and
      the mechanical strength influenced the tissue adhesiveness of the hydrogels. The
      hydrogels showed the adhesiveness ranging from 3- to 20-fold that of fibrin glue
      (Greenplast(r)). The hemostatic ability of the hydrogels was evaluated on the
      basis that bleeding from liver defects was significantly arrested by the combined
      effect of the adhesiveness of the hydrogels and the hemostatic property of the
      chitosan materials. The enzymatic crosslinking method enabled the water-soluble
      chitosan to rapidly form hydrogels within 5s of an incision into the skin of
      rats. Histological results demonstrated that the CPT hydrogels showed superior
      healing effects in the skin incision when compared to suture, fibrin glue and
      cyanoacrylate. By 2weeks post-implantation, the wound was completely recovered,
      with a newly formed dermis, due to the presence of the CPT hydrogels in the
      incision. These results suggest that the in situ curable chitosan hydrogels are
      very interesting and promising tissue adhesive devices for biomedical
      applications.

PMID- 22617741
TI  - Thick collagen-based 3D matrices including growth factors to induce neurite
      outgrowth.
AB  - Designing synthetic microenvironments for cellular investigations is a very
      active area of research at the crossroads of cell biology and materials science.
      The present work describes the design and functionalization of a three
      dimensional (3D) culture support dedicated to the study of neurite outgrowth from
      neural cells. It is based on a dense self-assembled collagen matrix stabilized by
      100-nm-wide interconnected native fibrils without chemical crosslinking. The
      matrices were made suitable for cell manipulation and direct observation in
      confocal microscopy by anchoring them to traditional glass supports with a
      calibrated thickness of ~50MUm. The matrix composition can be readily adapted to
      specific neural cell types, notably by incorporating appropriate neurotrophic
      growth factors. Both PC-12 and SH-SY5Y lines respond to growth factors (nerve
      growth factor and brain-derived neurotrophic factor, respectively) impregnated
      and slowly released from the support. Significant neurite outgrowth is reported
      for a large proportion of cells, up to 66% for PC12 and 49% for SH-SY5Y. It is
      also shown that both growth factors can be chemically conjugated (EDC/NHS)
      throughout the matrix and yield similar proportions of cells with longer neurites
      (61% and 52%, respectively). Finally, neurite outgrowth was observed over several
      tens of microns within the 3D matrix, with both diffusing and immobilized growth
      factors.

PMID- 22617742
TI  - Simultaneous regeneration of articular cartilage and subchondral bone induced by
      spatially presented TGF-beta and BMP-4 in a bilayer affinity binding system.
AB  - Subchondral defect repair is a multitask challenge requiring the simultaneous
      regeneration of cartilage and bone. Herein, we describe the features of a
      hydrogel system designed to simultaneously induce the endogenous regeneration of
      hyaline cartilage and subchondral bone. The system was constructed as two layers,
      spatially presenting the chondroinductive transforming growth factor-beta1 (TGF
      beta1) in one layer and the osteoinductive bone morphogenetic protein-4 (BMP-4)
      in a second layer, via affinity binding to the matrix. Human mesenchymal stem
      cells seeded in the bilayer system differentiated into chondrocytes and
      osteoblasts in the respective layers, confirming the spatial presentation and
      prolonged activity of TGF-beta1 and BMP-4. Administration of the bilayer system
      with affinity-bound TGF-beta1 and BMP-4 (with no cells) into a subchondral defect
      in rabbits induced endogenous regeneration of articular cartilage and the
      subchondral bone underneath within 4weeks. Cartilage extracellular matrix
      proteoglycans were found in the top layer, with no mineralization, whereas the
      layer underneath consisted of newly formed woven bone. The results indicate that
      stem cells migrating into the defect are able to sense the biological cues
      spatially presented in the hydrogel and respond by differentiation into the
      appropriate cell lineage. The strategy has a real translational potential for
      repairing osteochondral defects in humans as it is acellular and can be implanted
      via a minimally invasive method.

PMID- 22617743
TI  - Neuromyelitis optica.
AB  - Neuromyelitis optica (NMO) is a disabling inflammatory condition that targets
      astrocytes in the optic nerves and spinal cord. Neuro-ophthalmologists must be
      particularly aware of this disorder because about half of patients present as
      isolated unilateral optic neuritis months or years before a disease-defining and
      often crippling bout of myelitis. NMO is easily confused with multiple sclerosis
      because it is characterized by relapses that lead to stepwise accrual of
      deficits. The best predictor of conversion from optic neuritis to clinical
      definite NMO is the presence of a serum antibody to aquaporin-4 called NMO-IgG.
      However, this test is currently only about 75% sensitive. Suspicion of NMO should
      be high in patients who present with vision of light perception or worse or who
      are left with acuity of 20/50 or worse after optic neuritis and in those with
      simultaneous bilateral optic neuritis or recurrent attacks. Acute NMO relapses
      are generally treated with high-dose intravenous steroids, with plasma exchange
      often used as a rescue therapy for those who do not respond. Preventative
      strategies against relapses currently use broad-spectrum or selective B
      lymphocyte immune suppression, but their use is based on small, generally
      uncontrolled studies. Hopefully, the future will bring more sensitive tools for
      defining risk and predicting outcome, as well as more targeted and effective
      forms of therapy.

PMID- 22617744
TI  - Monocular vision loss and headache in a 60-year-old liver transplant patient.

PMID- 22617745
TI  - Orbital radiation therapy for thyroid eye disease.

PMID- 22617746
TI  - Interventional neuro-ophthalmology:  not an oxymoron.

PMID- 22617749
TI  - Role of megalin and the soluble form of its ligand RAP in Cd-metallothionein
      endocytosis and Cd-metallothionein-induced nephrotoxicity in vivo.
AB  - Orally administered Cd is predominantly distributed to the intestine, and the
      majority of this mucosal Cd is bound to metallothionein (MT). MT attenuates heavy
      metal-induced cytotoxicity by sequestering these metals and lowering their
      intracellular concentrations. In addition, MT acts as an extracellular
      transporter of orally administered Cd to the kidney. Because of its low molecular
      weight, the Cd-MT complex is freely filtered at the glomerulus, and the filtered
      Cd-MT is then incorporated into renal proximal tubular cells. Megalin, a
      multiligand endocytic receptor (also known as low-density lipoprotein receptor
      related protein 2 or Lrp2), acts as the receptor for Cd-MT in a renal proximal
      tubular cell model. Here, we used the soluble form of 39-kDa receptor-associated
      protein (sRAP; also known as Lrpap1), a ligand of megalin, to inhibit megalin
      function, and then analyzed the effect of megalin loss on Cd-MT distribution and
      Cd-MT-induced nephrotoxicity in an animal model. Administration of sRAP to mice
      caused acute loss of megalin function by removing megalin in the brush border
      membrane. The pre-injection of sRAP decreased renal Cd content and decreased Cd
      MT-induced kidney damage. Our results demonstrate that sRAP reduces Cd-MT-induced
      kidney toxicity in vivo.

PMID- 22617751
TI  - Nonalcoholic fatty liver disease and lipids.
AB  - PURPOSE OF REVIEW: This article reviews the mechanisms leading to the development
      of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis
      (NASH) and the effects of hypoglycaemic and lipid-lowering therapies on
      NAFLD/NASH. RECENT FINDINGS: The interaction of lipogenesis, fatty acid
      oxidation, inflammation, endoplasmic reticulum stress and hepatic insulin
      resistance contribute to the pathogenesis of NAFLD/NASH. Few large scale clinical
      trials exist with biopsy or magnetic resonance endpoints as opposed to
      ultrasonographic and transaminase endpoints. Trial evidence that exists supports
      the utility of weight loss, metformin, thiazolidinediones, fibrates, niacin,
      ezetimibe and statins in improving the steatosis component of NAFLD/NASH though
      with less or minimal effects on the fibrotic component of NASH. SUMMARY:
      Hypoglycaemic and lipid-lowering therapies may have a role in the treatment of
      NAFLD/NASH but large scale endpoint trials remain to be performed.

PMID- 22617752
TI  - Early growth and postprandial glucose, insulin, lipid and inflammatory responses
      in adulthood.
AB  - PURPOSE OF REVIEW: Epidemiological findings suggest that prenatal and postnatal
      growth is associated with later health outcomes including cardiovascular disease
      and type 2 diabetes. It has been suggested that these associations are mediated
      through classical risk factors, for example dyslipidemia. Despite extensive
      epidemiological investigations, only limited data are available on the long-term
      influences of early growth on postprandial responses, although postprandial
      levels of many risk factors have been proposed to be more important than fasting
      levels in disease process. This review focuses on recent studies evaluating the
      effect of early growth on postprandial responses. RECENT FINDINGS: Current
      evidence from postprandial studies shows that individuals who were small at birth
      or grew slowly during infancy have elevated postprandial insulin and triglyceride
      responses. However, early growth does not seem to affect postprandial
      inflammatory markers. It is likely that both liver programming and abnormalities
      in insulin-sensitive tissues play key roles in explaining these elevated
      responses. SUMMARY: Recent studies suggest that slow growth during early life has
      an adverse effect on postprandial metabolism, and predicts higher insulin and
      triglyceride responses. These elevated postprandial responses might be one
      underlying mechanism explaining the increased risk of cardiovascular disease and
      type 2 diabetes associated with nonoptimal early growth.

PMID- 22617750
TI  - Association of systemic inflammation with marked changes in particulate air
      pollution in Beijing in 2008.
AB  - Many studies have linked ambient fine particulate matter (aerodynamic diameters
      less than 2.5 MUm, PM2.5) air pollution to increased morbidity and mortality of
      cardiovascular diseases in the general population, but the biologic mechanisms of
      these associations are yet to be elucidated. In this study, we aimed to evaluate
      the relationship between daily variations in exposure to PM2.5 and inflammatory
      responses in mice during and for 2 months after the Beijing Olympic Games. Male
      C57BL/6 mice were exposed to Beijing PM2.5 or filtered air (FA) in 2008 during
      the 2 months of Beijing Olympic and Paralympic Games, and for 2 months after the
      end of the Games. During the Games, circulating monocyte chemoattractant protein
      1 and interleukin 6 were increased significantly in the PM2.5 exposure group,
      when compared with the FA control group, although there were no significant inter
      group differences in tumor necrosis factor-alpha or interferon-gamma, or in
      macrophages, neutrophils or lymphocytes in the spleen or thymus between these 2
      groups. However, macrophages were significantly increased in the lung and
      visceral fat with increasing PM2.5. After the Olympic Games, there were no
      significant PM2.5-associated differences for macrophages, neutrophils or
      lymphocytes in the thymus, but macrophages were significantly elevated in the
      lung, spleen, subcutaneous and visceral fat with increasing PM2.5, and the
      numbers of macrophages were even higher after than those during the Games.
      Moreover, the number of neutrophils was markedly higher in the spleen for the
      PM2.5-exposed- than the FA-group. These data suggest that short-term increases in
      exposure to ambient PM2.5 leads to increased systemic inflammatory responses,
      primarily macrophages and neutrophils in the lung, spleen, and visceral adipose
      tissue. Short-term air quality improvements were significantly associated with
      reduced overall inflammatory responses.

PMID- 22617753
TI  - Principles of health economic evaluations of lipid-lowering strategies.
AB  - PURPOSE OF REVIEW: Policy decision-making in cardiovascular disease is
      increasingly informed by the results generated from decision-analytic models
      (DAMs). The methodological approaches and assumptions used in these DAMs impact
      on the results generated and can influence a policy decision based on a cost per
      quality-adjusted life year (QALY) threshold. Decision makers need to be provided
      with a clear understanding of the key sources of evidence and how they are used
      in the DAM to make an informed judgement on the quality and appropriateness of
      the results generated. RECENT FINDINGS: Our review identified 12 studies
      exploring the cost-effectiveness of pharmaceutical lipid-lowering interventions
      published since January 2010. All studies used Markov models with annual cycles
      to represent the long-term clinical pathway. Important differences in the model
      structures and evidence base used within the DAMs were identified. Whereas the
      reporting standards were reasonably good, there were many instances when
      reporting of methods could be improved, particularly relating to baseline risk
      levels, long-term benefit of treatment and health state utility values. SUMMARY:
      There is a scope for improvement in the reporting of evidence and modelling
      approaches used within DAMs to provide decision makers with a clearer
      understanding of the quality and validity of the results generated. This would be
      assisted by fuller publication of models, perhaps through detailed web
      appendices.

PMID- 22617754
TI  - The role of pathway-selective insulin resistance and responsiveness in diabetic
      dyslipoproteinemia.
AB  - PURPOSE OF REVIEW: Type 2 diabetes mellitus (T2DM) and related syndromes exhibit
      a deadly triad of dyslipoproteinemia, which leads to atherosclerosis,
      hyperglycemia, which causes microvascular disease, and hypertension. These
      features share a common, but unexplained, origin--namely, pathway-selective
      insulin resistance and responsiveness (SEIRR). Here, we review recent work on
      hepatic SEIRR indicating that deranged insulin signaling may have a remarkably
      simple molecular basis. RECENT FINDINGS: Comprehensive examination of a set of 18
      insulin targets revealed that T2DM liver in vivo exhibits a specific defect in
      the ability of the NAD(P)H oxidase 4 (NOX4) to inactivate protein tyrosine
      phosphatase gene family members after stimulation with insulin, and that
      impairment of this single molecule, NOX4, in cultured hepatocytes recapitulates
      all features of hepatic SEIRR in vivo. These features include insulin-stimulated
      generation of an unusual monophosphorylated form of AKT at Thr308 (pT308-AKT)
      with only weak phosphorylation at Ser473, impaired insulin-stimulated pathways
      for lowering plasma levels of lipids and glucose, but continued lipogenic
      pathways and robust extracellular signal-regulated kinase activation. This new
      study, in combination with important prior work, provides clues to several long
      standing mysteries, such as how AKT might regulate lipid-lowering and glucose
      lowering pathways that become insulin-resistant but also lipogenic pathways that
      remain insulin-responsive, as well as a potential role for NOX4 in insulin
      stimulated generation of oxysterol ligands for LXR, a key lipogenic factor.
      SUMMARY: These findings suggest a unified molecular explanation for fatty liver,
      atherogenic dyslipoproteinemia, hyperglycemia, and hence accelerated
      atherosclerosis and microvascular disease in T2DM, obesity, and related syndromes
      of positive caloric imbalance.

PMID- 22617755
TI  - Determinants of VLDL-triglycerides production.
AB  - PURPOSE OF REVIEW: Plasma free fatty acids (FFA) are major substrates for hepatic
      VLDL-triglycerides (VLDL-TG) production. In addition, it is a common belief that
      VLDL-TG production is a substrate driven process primarily determined by systemic
      FFA delivery. This review summarizes recent research of our understanding of the
      regulation of VLDL-TG production. RECENT FINDINGS: Recent studies have shown that
      increasing FFA flux is not inevitably associated with increased VLDL-TG
      production. Exercise induced increase in FFA flux resulting in unchanged VLDL-TG
      production in lean patients as well as in obese patients with increased hepatic
      fat despite exercise reduced hepatic fat content. With respect to the other
      inseparable conditions of insulin resistance and hyperinsulinemia, recent studies
      demonstrate that increased hepatic VLDL-TG production precedes the insulin
      resistance-associated impairment of the regulation of hepatic glucose production,
      whereas isolated chronic hyperinsulinemia (insulinoma) was not associated with
      increased VLDL-TG production. Insulin has been shown to have acute potent
      temporary suppressing effect on VLDL-TG production and new data demonstrates that
      increased glucagon reduces VLDL-TG production. Finally, recent studies indicate
      that sex hormones, oestrogen and testosterone, have no or very modest impact on
      VLDL-TG production. SUMMARY: Regulation of hepatic VLDL-TG production involves
      interplay between systemic FFA delivery, hormonal, and nutritional factors that
      act in concert with hepatic fatty acid handling to regulate short-term and long
      term VLDL-TG production. The results of recent studies underscore that our
      current understanding of these relationships is complex and needs further
      research.

PMID- 22617756
TI  - Prophylactic and therapeutic combination effects of rimantadine and oseltamivir
      against influenza virus A (H3N2) infection in mice.
AB  - The combined effect of rimantadine and oseltamivir in a prophylactic context
      (therapy beginning 4 h pre-virus infection) and therapeutic context (therapy
      started at 24 h post-viral inoculation) course on influenza H3N2 virus infection
      in mice was studied. In the prophylactic course 5 and 10 mg/kg/day rimantadine
      with 0.2 and 0.4 mg/kg/day (25:1 dose ratio) oseltamivir showed a protection
      index (PI) of 79.6% and 75%, respectively and a mean survival time (MST) of 13.1
      and 12.9 days. The individual effects of the same doses ranged from 0% to 33.3%
      PI and 8.2 to 10.3 days MST, respectively. Lung virus titers were decreased 630
      fold in the combination-treated groups as compared to monotherapy and placebo
      groups. The reduction of surface lung pathology in combination-treated groups
      demonstrated a protective effect for the combination of both antivirals. In the
      therapeutic course 5 and 10 mg/kg rimantadine combined with 0.2 and 0.4 mg/kg
      oseltamivir showed no beneficial effect. At higher dosage (0.8, 1.6, 3.2 mg/kg
      oseltamivir and 20, 40, 80 mg/kg rimantadine) preserving the 25:1 ratio, the
      resultant PI ranged from 57.6% to 80.5% and the MST was 12.8-13.4 days. Used
      alone at the same doses the compounds' protection varied between 10.7% and 71.8%
      PI, MST 9.8-12.8 days (8.7 days in PBS control). Compared to vehicle and
      individual treatment, a decrease in infectious viral titers of up to 1000-fold
      and other viral pneumonia parameters were also recorded. The therapeutic effect
      of the drugs' optimal effective doses combinations was characterized as
      synergistic. Survival of animals was 81.2-100% and MST was extended by 5-7 days
      compared to placebos. Monotherapy protection was from 9.1% to a maximum of 56.5%,
      MST being prolonged only by 1.3-4.2 days compared to 7.5 days in the PBS control
      group. Lung viral titers were decreased 1445-fold for the most efficacious
      combination groups and a significant reduction in lung parameters was observed.
      These data emphasize that prophylactic and therapeutic courses using a
      combination of oseltamivir and rimantadine have a significant protective effect
      in mice experimentally infected with drug-sensitive influenza virus A (H3N2).

PMID- 22617757
TI  - Can local Erythropoietin administration enhance bone regeneration in
      osteonecrosis of femoral head?
AB  - Osteonecrosis of femoral head (ONFH) is a challenging disease. Regardless of
      underlying causes, the ultimate result in all cases is disruption of femoral head
      blood supply. Once the disease starts, it is progressive in 80% of cases. Since
      the majority of the affected individuals are young, every effort should be
      focused on preserving the patients own femoral head. These years, the role of
      angiogenic growth factors has been investigated with promising results in animal
      models of ONFH. Erythropoietin (EPO) is a well known hormone that has been used
      in treatment of chronic anemia for many years with few side effects. Considering
      the angiogenic properties of EPO, we hypothesize that local delivery of
      recombinant human EPO during core decompression will enhance bone regeneration in
      ONFH. In this way we also can avoid systemic side effects of EPO.

PMID- 22617758
TI  - A new concept to measure cell proliferation using Fourier transform infrared
      spectroscopy.
AB  - In our laboratory, we recently developed a new technique to measure cell
      proliferation that is based on infrared spectro-photometry and the density of
      cell culture medium. The fluid exchange between intra and extra cellular
      environments is the key to our method. Using this technique, we found that cell
      proliferation assessment may be performed much faster than presently existing
      methods, using two separate pieces of equipment (a cell culture incubator and an
      interferometer). We confirmed the viability of our method using five different
      cell lines, breast cancer cells (BT20), mouse normal embryonic fibroblast (NEF)
      as well as those expressing E6/E7 onco-proteins of human papillomavirus (HPV)
      type 16, and a human cervical cancer cell line (HeLa). Based on our findings, we
      propose the design of a mini-incubator allowing cell culture as well as infrared
      spectra collection of the culture medium, as an accessory to the FTIR work bench,
      which would become a promising arrangement for continuous cell proliferation
      monitoring. Moreover, the use of the collected culture medium will be highly
      efficient in terms of reducing both experimental time and cost.

PMID- 22617759
TI  - Murine model of allergen induced asthma.
AB  - Asthma is a major cause of morbidity and mortality, affecting some 300 million
      people throughout the world (1). More than 8% of the US population has asthma,
      with the prevalence increasing (2). As with other diseases, animal models of
      allergic airway disease greatly facilitate understanding of the underlying
      pathophysiology, help identify potential therapeutic targets, and allow
      preclinical testing of possible new therapies. Models of allergic airway disease
      have been developed in several animal species, but murine models are particularly
      attractive due to the low cost, ready availability, and well-characterized immune
      systems of these animals (3). Availability of a variety of transgenic strains
      further increases the attractiveness of these models (4). Here we describe two
      murine models of allergic airway disease, both employing ovalbumin as the
      antigen. Following initial sensitization by intraperitoneal injection, one model
      delivers the antigen challenge by nebulization, the other by intratracheal
      delivery. These two models offer complementary advantages, with each mimicking
      the major features of human asthma (5). The major features of acute asthma
      include an exaggerated airway response to stimuli such as methacholine (airway
      hyperresponsiveness; AHR) and eosinophil-rich airway inflammation. These are also
      prominent effects of allergen challenge in our murine models (5,6), and we
      describe techniques for measuring them and thus evaluating the effects of
      experimental manipulation. Specifically, we describe both invasive (7) and non
      invasive (8) techniques for measuring airway hyperresponsiveness as well as
      methods for assessing infiltration of inflammatory cells into the airways and the
      lung. Airway inflammatory cells are collected by bronchoalveolar lavage while
      lung histopathology is used to assess markers of inflammation throughout the
      organ. These techniques provide powerful tools for studying asthma in ways that
      would not be possible in humans.

PMID- 22617760
TI  - A method for energy window optimization for quantitative tasks that includes the
      effects of model-mismatch on bias: application to Y-90 bremsstrahlung SPECT
      imaging.
AB  - Quantitative Yttrium-90 ((90)Y) bremsstrahlung single photon emission computed
      tomography (SPECT) imaging has shown great potential to provide reliable
      estimates of (90)Y activity distribution for targeted radionuclide therapy
      dosimetry applications. One factor that potentially affects the reliability of
      the activity estimates is the choice of the acquisition energy window. In
      contrast to imaging conventional gamma photon emitters where the acquisition
      energy windows are usually placed around photopeaks, there has been great
      variation in the choice of the acquisition energy window for (90)Y imaging due to
      the continuous and broad energy distribution of the bremsstrahlung photons. In
      quantitative imaging of conventional gamma photon emitters, previous methods for
      optimizing the acquisition energy window assumed unbiased estimators and used the
      variance in the estimates as a figure of merit (FOM). However, for situations,
      such as (90)Y imaging, where there are errors in the modeling of the image
      formation process used in the reconstruction there will be bias in the activity
      estimates. In (90)Y bremsstrahlung imaging this will be especially important due
      to the high levels of scatter, multiple scatter, and collimator septal
      penetration and scatter. Thus variance will not be a complete measure of
      reliability of the estimates and thus is not a complete FOM. To address this, we
      first aimed to develop a new method to optimize the energy window that accounts
      for both the bias due to model-mismatch and the variance of the activity
      estimates. We applied this method to optimize the acquisition energy window for
      quantitative (90)Y bremsstrahlung SPECT imaging in microsphere brachytherapy.
      Since absorbed dose is defined as the absorbed energy from the radiation per unit
      mass of tissues in this new method we proposed a mass-weighted root mean squared
      error of the volume of interest (VOI) activity estimates as the FOM. To calculate
      this FOM, two analytical expressions were derived for calculating the bias due to
      model-mismatch and the variance of the VOI activity estimates, respectively. To
      obtain the optimal acquisition energy window for general situations of interest
      in clinical (90)Y microsphere imaging, we generated phantoms with multiple tumors
      of various sizes and various tumor-to-normal activity concentration ratios using
      a digital phantom that realistically simulates human anatomy, simulated (90)Y
      microsphere imaging with a clinical SPECT system and typical imaging parameters
      using a previously validated Monte Carlo simulation code, and used a previously
      proposed method for modeling the image degrading effects in quantitative SPECT
      reconstruction. The obtained optimal acquisition energy window was 100-160 keV.
      The values of the proposed FOM were much larger than the FOM taking into account
      only the variance of the activity estimates, thus demonstrating in our experiment
      that the bias of the activity estimates due to model-mismatch was a more
      important factor than the variance in terms of limiting the reliability of
      activity estimates.

PMID- 22617762
TI  - The vascular endothelium: a wonderful network: introduction.

PMID- 22617761
TI  - Is abdominal compression useful in lung stereotactic body radiation therapy? A
      4DCT and dosimetric lobe-dependent study.
AB  - PURPOSE: To determine the usefulness of abdominal compression in lung
      stereotactic body radiation therapy (SBRT) depending on lobe tumor location.
      MATERIALS AND METHODS: Twenty-seven non-small cell lung cancer patients were
      immobilized in the Stereotactic Body FrameTM (Elekta). Eighteen tumors were
      located in an upper lobe, one in the middle lobe and nine in a lower lobe (one
      patient had two lesions). All patients underwent two four-dimensional computed
      tomography (4DCT) scans, with and without abdominal compression. Three
      dimensional tumor motion amplitude was determined using manual landmark
      annotation. We also determined the internal target volume (ITV) and the influence
      of abdominal compression on lung dose-volume histograms. RESULTS: The mean
      reduction of tumor motion amplitude was 3.5 mm (p = 0.009) for lower lobe tumors
      and 0.8 mm (p = 0.026) for upper/middle lobe locations. Compression increased
      tumor motion in 5 cases. Mean ITV reduction was 3.6 cm(3) (p = 0.039) for lower
      lobe and 0.2 cm(3) (p = 0.048) for upper/middle lobe lesions. Dosimetric gain of
      the compression for lung sparing was not clinically relevant. CONCLUSIONS: The
      most significant impact of abdominal compression was obtained in patients with
      lower lobe tumors. However, minor or negative effects of compression were
      reported for other patients and lung sparing was not substantially improved. At
      our institute, patients with upper or middle lobe lesions are now systematically
      treated without compression and the usefulness of compression for lower lobe
      tumors is evaluated on an individual basis.

PMID- 22617763
TI  - Vascular heterogeneity in the kidney.
AB  - Blood vessels and their endothelial lining are uniquely adapted to the needs of
      the underlying tissue. The structure and function of the vasculature varies both
      between and within different organs. In the kidney, the vascular architecture is
      designed to function both in oxygen/nutrient delivery and filtration of blood
      according to the homeostatic needs of the body. Here, we review spatial and
      temporal differences in renal vascular phenotypes in both health and disease.

PMID- 22617764
TI  - Endothelial control of vasomotor tone: the kidney perspective.
AB  - Endothelial cells are essential regulators of vascular tone. They accomplish this
      by sensing humoral mediators and transducing their effects to the underlying
      vascular smooth muscle as well as by synthesizing vasoactive molecules that act
      in a paracrine fashion. In the kidney, the local release of these endothelial
      mediators, together with the concourse of specialized endothelial cells in the
      glomerulus, contribute to regulate renal blood flow, glomerular filtration, and
      tubular function that are intimately linked to sodium balance because they
      mutually influence each other. Ultimately, renal circulation and tubular function
      have a profound influence in systemic blood pressure as a result of the overall
      regulation of volume homeostasis.

PMID- 22617765
TI  - A primer on the role of microRNAs in endothelial biology and vascular disease.
AB  - Endothelial cells are highly proliferative and motile during vascular
      development. However, as blood vessels mature and stabilize the endothelial
      lining becomes quiescent, and cell-cell interactions among endothelial cells
      generate a stable barrier between the blood and tissue. Rather than simply
      functioning as an inert barrier, endothelial cells constantly sense and respond
      to environmental cues. Activation of the endothelium can promote the loss of cell
      cell adhesion and an increase in the motility and proliferation of the
      endothelium. This process is requisite for tissue repair, but also plays a role
      in vascular pathogenesis and is especially relevant to kidney injury. The
      molecular mechanisms that facilitate these phenotypic alterations are only
      partially understood. Recent work has shown that microRNAs can modulate
      endothelial phenotype. These new insights have shed light on the complex
      mechanisms that endothelial cells use to respond to environmental stimuli. This
      review addresses the known roles that microRNAs play in controlling angiogenic
      and inflammatory signals in endothelial cells, and illustrates that microRNAs are
      important modulators of endothelial function in vascular disease, and therefore
      represent promising therapeutic targets.

PMID- 22617767
TI  - Flow-dependent endothelial function and kidney dysfunction.
AB  - The vascular endothelium constantly integrates biomechanical and humoral signals
      and responds by secreting or metabolizing multiple factors that act in an
      autocrine or paracrine manner on the vasculature and adjacent tissues. Several
      studies have documented the effects of blood flow on renal endothelial cells and
      its effects on the pathophysiology of the kidney. In contrast, less is known
      about the effects of acute flow cessation on renal endothelium and kidney
      function. Here we review our current knowledge on flow cessation, endothelial
      function, and kidney dysfunction in the context of two clinically relevant
      settings, namely, the no-reflow phenomenon, observed during periods of renal warm
      ischemia, and the cold storage of kidney transplants.

PMID- 22617766
TI  - Gene regulation in the vascular endothelium: why epigenetics is important for the
      kidney.
AB  - We now appreciate that the vascular endothelium plays a crucial role in
      regulating normal blood vessel physiology in the kidney. The gene products
      responsible are commonly expressed exclusively, or preferentially, in this cell
      type. However, despite the importance of regulated gene expression in the
      vascular endothelium, relatively little is known about the mechanisms that
      restrict endothelial-specific gene expression to this cell type. Even less is
      known about how gene expression might be restricted to endothelial cells of
      discrete regions of the kidney, such as the glomerulus or vasa recta. Although
      significant progress has been made toward understanding the regulation of
      endothelial genes through cis/trans paradigms, it has become apparent that
      additional mechanisms also must be operative. Classic models of transcription in
      vascular endothelial cells, specifically the cis/trans paradigm, have
      limitations. For instance, how does the environment have chronic effects on gene
      expression in endothelial cells after weeks or years? When an endothelial cell
      divides, how is this information transmitted to daughter cells? Chromatin-based
      mechanisms, including cell-specific DNA methylation patterns and post
      translational histone modifications, recently were shown to play important roles
      in gene expression. This review investigates the involvement of epigenetic
      regulatory mechanisms in vascular endothelial cell-specific gene expression using
      endothelial nitric oxide synthase as a prototypical model.

PMID- 22617769
TI  - The endothelium in diabetic nephropathy.
AB  - The long-term complications of diabetes are characterized by pathologic changes
      in both the microvasculature and conduit vessels. Although the fenestrated
      glomerular endothelium classically has been viewed as providing little in the way
      of an impediment to macromolecular flow, increasing evidence illustrates that
      this is not the case. Rather, hyperglycemia-mediated endothelial injury may
      predispose to albuminuria in diabetes both through direct effects and through
      bidirectional communication with neighboring podocytes. Although neo-angiogenesis
      of the glomerular capillaries may be a feature of early diabetes, particularly in
      the experimental setting, loss of capillaries in the glomerulus and in the
      interstitium are key events that each correlate closely with declining glomerular
      filtration rate in patients with diabetic nephropathy. The hypoxic milieu that
      follows the microvascular rarefaction provides a potent stimulus for
      fibrogenesis, leading to the glomerulosclerosis and tubulointerstitial fibrosis
      that characterize advanced diabetic kidney disease. Given the pivotal role the
      endothelium plays in both the development and the progression of diabetic
      nephropathy we need effective strategies that prevent its loss or accelerate its
      regeneration. Such advances likely will lead not only to improved tissue
      oxygenation and reduced fibrosis, but also to improved long-term renal function.

PMID- 22617768
TI  - Endothelium under stress: local and systemic messages.
AB  - Endothelial responses to stressors are nonuniform and follow the rules of stress
      induced hormesis. Responses to the same stressor, depending on its intensity, can
      range from pro-regenerative to pro-lethal. Exposure to sublethal stressors
      induces a programmed response that results in stress resistance, whereas a lethal
      level of a stressor accelerates cell demise. Diverse stressors turn on several
      default programs within the cells; such programs tend to induce anti-oxidative
      defenses and anti-inflammatory and pro-survival systems, whereas others tend to
      switch on pro-apoptotic systems. The response of the kidney endothelium to
      various forms of acute kidney injury follows these general principles. It is
      characterized by a proinflammatory pattern that includes up-regulation of
      different adhesion molecules promoting endothelial-leukocyte interactions,
      generation of reactive oxygen species, with formation of oxidative and
      nitrosative stress and mitochondrial damage. Simultaneously, a series of adaptive
      mechanisms, both local and systemic, are ignited. Stressed endothelial cells
      broadcast distress signals systemically; these signals can be directed toward the
      restoration of homeostasis or aggravation of the original insult.

PMID- 22617770
TI  - Endothelial cells and thrombotic microangiopathy.
AB  - Thrombotic microangiopathy represents the clinical picture of thrombocytopenia
      and hemolytic anemia in the setting of small blood vessel thrombosis, accompanied
      by varying degrees of organ dysfunction. Well known to both nephrologists and
      hematologists alike, among the most common and best-studied thrombotic
      microangiopathy are hemolytic-uremic syndrome and thrombotic thrombocytopenic
      purpura. Despite sharing a strong clinical and historical relationship, these
      disorders represent distinct clinical and pathophysiological entities. This
      article reviews recent progress into the pathogenesis of thrombotic
      thrombocytopenic purpura and hemolytic-uremic syndrome, focusing on events taking
      place at the endothelial surface.

PMID- 22617771
TI  - Bone marrow cell therapies for endothelial repair and their relevance to kidney
      disease.
AB  - Endothelial injury is a characteristic finding in chronic kidney disease and is
      associated with both markedly increased cardiovascular risk and chronic kidney
      disease progression. The past decade has seen a remarkable surge of interest in
      the role of bone marrow-derived cells for the protection, repair, and
      regeneration of injured endothelium. In particular, despite controversies
      regarding their mechanisms of action, endothelial progenitor cells have garnered
      considerable attention, with multiple reports suggesting that these cells exhibit
      remarkable pro-angiogenic effects. Recent advances in our understanding of how
      the bone marrow responds to endothelial injury now suggest that multiple bone
      marrow cell populations, including both endothelial progenitor cells and a novel
      group of cells called early outgrowth cells, promote endothelial repair and
      regeneration through different, yet complementary, mechanisms. Moreover, certain
      subsets of bone marrow-derived cells also appear to have novel, potent,
      angiogenesis-independent tissue-protective properties. The bone marrow should
      thus now be viewed not only as a hematopoiesis organ, but also as a rich
      reservoir of cells capable of protecting and even regenerating nonhematopoietic
      tissues such as the kidney. To harness the prognostic and therapeutic potential
      of the bone marrow, the renal community must be aware of recent advances in our
      understanding of the nature and therapeutic potential of these cells.

PMID- 22617773
TI  - Antitumor effects of FP3 in combination with capecitabine on PDTT xenograft
      models of primary colon carcinoma and related lymphatic and hepatic metastases.
AB  - FP3 is an engineered protein which contains the extracellular domain 2 of VEGF
      receptor 1 (Flt-1) and extracellular domain 3 and 4 of VEGF receptor 2 (Flk-1,
      KDR) fused to the Fc portion of human immunoglobulin G 1. Previous studies
      demonstrated its antiangiogenic effects in vitro and in vivo, and its antitumor
      activity in vivo. In this study, patient-derived tumor tissue (PDTT) xenograft
      models of primary colon carcinoma and lymphatic and hepatic metastases were
      established for assessment of the antitumor activity of FP3 in combination with
      capecitabine. Xenografts were treated with FP3, capecitabine, alone or in
      combination. After tumor growth was confirmed, volume and microvessel density in
      tumors were evaluated. Levels of VEGF, and PCNA in the tumor were examined by
      immunohistonchamical staining, level of thymidine phosphorylase (TP) was examined
      by ELISA, and levels of related cell signaling pathways proteins expression were
      examined by western blotting. FP3 in combination with capecitabine showed
      significant antitumor activity in three xenograft models (primary colon
      carcinoma, lymphatic metastasis, and hepatic metastasis). The microvessel density
      in tumor tissues treated with FP3 in combination with capecitabine was lower than
      that of the control. Antitumor activity of FP3 in combination with capecitabine
      was significantly higher than that of each agent alone in three xenograft models
      (primary colon carcinoma, lymphatic metastasis, and hepatic metastasis). This
      study indicated that addition of FP3 to capecitabine significantly improved tumor
      growth inhibition in the PDTT xenograft models of primary colon carcinoma and
      lymphatic and hepatic metastases.

PMID- 22617774
TI  - HMGB1 was a pivotal synergistic effecor for CpG oligonucleotide to enhance the
      progression of human lung cancer cells.
AB  - High-mobility group box 1 (HMGB1) has been implicated in a variety of
      biologically important processes, including transcription, DNA repair,
      differentiation, development, and extracellular signaling. However, the potential
      role of HMGB1 in tumor biology still remains intractable. Our previous study
      showed that TLR9 response to CpG oligonucleotide (ODN) in 95D human lung cancer
      cells could enhance their growth and invasive potential in vitro and in vivo.
      Here we found that CpG ODN stimulation to 95D cells induced the secretion of
      HMGB1 in a dose dependent manner. We further showed that blockade of
      extracellular HMGB1 using A box peptide and ethyl pyruvate significantly
      abrogated the CpG ODN enhanced progression of 95D cells. Interestingly, we found
      that HMGB1 alone or acted synergistic with CpG ODN could enhance the progression
      of 95D cells. Notably, we revealed that RAGE and TLR4 were critical for HMGB1 to
      exert the synergistic function. We observed a MyD88-dependent upregulation of
      matrix metalloproteinase (MMP) 2, MMP9 and cyclin-dependent kinase (CDK) 2 in 95D
      cells in response to HMGB1. These findings might further our understanding of
      TLR9 signaling in tumor biology and be helpful for developing HMGB1-based
      strategy against lung cancer.

PMID- 22617772
TI  - A positive-margin resection model recreates the postsurgical tumor
      microenvironment and is a reliable model for adjuvant therapy evaluation.
AB  - Up to 30% of cancer patients undergoing curative surgery develop local
      recurrences due to positive margins. Patients typically receive adjuvant
      chemotherapy, immunotherapy and/or radiation to prevent such relapses.
      Interestingly, evidence supporting these therapies is traditionally derived in
      animal models of primary tumors, thus failing to consider surgically induced
      tumor microenvironment changes that may influence adjuvant therapy efficacy. To
      address this consideration, we characterized a murine model of local cancer
      recurrence. This model was reproducible and generated a postoperative
      inflammatory tumor microenvironment that resembles those observed following human
      cancer surgery. To further validate this model, antagonists of two pro
      inflammatory mediators, TGFbeta and COX-2, were tested and found to be effective
      in decreasing the growth of recurrent tumors. We appreciated that preoperative
      TGFbeta inhibition led to wound dehiscence, while postoperative initiation of COX
      2 inhibition resulted in a loss of efficacy. In summary, although not an exact
      replica of all human cancer surgeries, our proposed local recurrence approach
      provides a biologically relevant and reliable model useful for preclinical
      evaluation of novel adjuvant therapies. The use of this model yields results that
      may be overlooked using traditional preclinical cancer models that fail to
      incorporate a surgical component.

PMID- 22617775
TI  - A feasibility study on gene therapy of pancreatic carcinoma with Ad-PUMA.
AB  - Pancreatic cancer is one of the most malignant tumors with high mortality and
      poor prognosis even with the aggressive conventional therapies. Biotherapy based
      on the understanding of tumorigenesis mechanism is ongoing to improve the
      outcomes of cancer patients. We sought here to evaluate the therapeutic potential
      of a proapoptotic gene, PUMA, in pancreatic cancer. We found that PUMA was
      differently expressed in a series of pancreatic ductal adenocarcinoma cancer cell
      lines, and adenovirus-mediated expression of PUMA (Ad-PUMA) in these cells
      resulted in massive apoptosis. PUMA was more potent than p53 in suppressing
      growth of cancer cells. RT-PCR and Western Blot revealed that exogenous PUMA was
      expressed 6 h after Ad-PUMA infection. Furthermore, we assessed the efficacy of
      Ad-PUMA combining anticancer drugs (5-fluorouracil, cisplatin, gemcitabine
      hydrochloride, respectively) in these pancreatic cancer cell lines. Data revealed
      that PUMA significantly sensitized pancreatic carcinoma cell lines to
      chemotherapeutics, which may be resulted from abundant apoptosis induction. In
      nude mice with PANC-1 xenografts, Ad-PUMA treatment significantly inhibited the
      tumor growth. These results suggest that PUMA is a potent molecular tool in
      suppressing tumor growth sensitizing pancreatic carcinoma cells to chemical
      drugs. PUMA plays roles in negatively regulating cancer cell growth and may be a
      promising tool for cancer biotherapy, with or without combination with
      chemotherapeutic agents.

PMID- 22617776
TI  - Prenatal diagnosis and molecular characterization of a novel locus for Dandy
      Walker malformation on chromosome 7p21.3.
AB  - We present three foetuses with Dandy-Walker malformation, intra-uterine growth
      restriction and multiple congenital abnormalities, who were studied by array
      based comparative genomic hybridization and revealed a novel locus on chromosome
      7p21.3. The association of pure chromosome 7p aberrations with Dandy-Walker
      malformation has rarely been reported. The present study suggests that the
      critical region associated with Dandy-Walker malformation is restricted to
      7p21.3, including the cerebellar disease associated genes NDUFA4 and PHF14.

PMID- 22617777
TI  - What have you done for yourself lately?

PMID- 22617778
TI  - The development of an educational intervention to address workplace bullying: a
      pilot study.
AB  - A growing body of research on workplace bullying which addresses the detrimental
      consequences of bullying in nursing has emerged. This quasi-experimental pilot
      study was aimed at examining the effect of an educational program provided to
      nursing staff on workplace bullying. The development of an educational program
      and use of a registered nurse educator in a group setting is an effective method
      for addressing workplace bullying.

PMID- 22617779
TI  - Orientation without walls: opening an acute care hospital.
AB  - Providing holistic orientation for all hospital personnel of a newly constructed
      acute care facility without patient presence proved challenging and rewarding to
      staff development educators. Early planning, multidisciplinary involvement of key
      stakeholders for hospital-wide and nursing orientation, and on-boarding of unit
      nursing educators shortly after unit nursing managers promoted success. Using an
      interdisciplinary approach to address hospital policies, procedures, and
      education ensured a quality healthcare facility in the community.

PMID- 22617780
TI  - Succeeding in the first year of practice: heed the wisdom of novice nurses.
AB  - The transition from student to nurse has been described as traumatic, confusing,
      and shocking. The difficulties encountered by the graduates have led to the
      premature termination of their first position, and sometimes they leave nursing
      altogether. To coach new nurses in preparation for their first year of practice
      using an appreciative inquiry framework, this study focused on the new graduates'
      perspective of the processes that enabled them to successfully integrate into
      their new role. From the analysis of 36 interviews, three themes were identified:
      "They were there for me," "There are no stupid questions," and "Nurturing the
      seeds." New nurses know what works for them; educators need to heed their wisdom.

PMID- 22617781
TI  - Predictors of new graduate nurses' organizational commitment during a nurse
      residency program.
AB  - Retaining newly graduated nurses is critical for organizations because of the
      significant cost of turnover. Since commitment to an organization is associated
      with decreased turnover intent, understanding factors that influence new
      graduates' organizational commitment is important. In a sample of nurse residency
      program participants, predictors of organizational commitment over time were
      explored. Perceptions of the work environment, particularly job satisfaction and
      job stress, were found to be most influential.

PMID- 22617782
TI  - Improving code blue response through the use of simulation.
AB  - In this research project, the response times to chest compressions, first
      defibrillation, and first dose of epinephrine in cardiac arrest were measured
      over a 3-month period through retrospective chart reviews. All nursing staff then
      participated in random, unannounced mock code blue drills using a high-fidelity
      patient simulator. After 3 months of code blue drills, the variables were again
      measured in patient code blue situations and compared with the response times
      before training. At the conclusion of this study, the response times for start of
      chest compressions and epinephrine administration improved significantly; the
      response time to defibrillation did not improve significantly. The response times
      were measured for an additional 3-month period to assess if the improvement was
      sustained.

PMID- 22617783
TI  - A student evaluation workshop with rural nursing preceptors.
AB  - Increasingly, clinicians and faculty members are motivated to provide students
      quality preceptorship placements in rural areas, particularly in light of the
      potential for recruitment of new graduates to underserved areas. Invariably,
      student performance evaluation is an onerous task for many preceptors and one in
      which they often feel ill-prepared. Rural preceptors may face additional
      challenges given the lesser availability of educational resources and
      professional development. In this article, the authors detail the development,
      pilot testing, and evaluation of a workshop on student evaluation that was
      created in collaboration with rural nurse preceptors.

PMID- 22617784
TI  - Assessing confidence in triage decision making: evaluation of an inventory in a
      sample of navy and civilian nurses.
AB  - Triage decision making and prioritizing nursing care are essential nursing skills
      in all clinical settings. The purpose of this study was to evaluate the
      psychometric properties of the Triage Decision Making Inventory in a sample of
      Navy and civilian nurses with diverse clinical specialties and years of clinical
      experience. Establishing reliability and validity allows staff development
      educators to evaluate training strategies that promote confidence in decision
      making among nurses of all specialty practices.

PMID- 22617785
TI  - Research priorities for nursing professional development: a modified e-Delphi
      study.
AB  - In 2010, the National Nursing Staff Development Organization Research Committee
      identified the need to delineate research priorities for nursing professional
      development (NPD). A Delphi study with 13 experts in NPD resulted in the
      identification of 24 priorities for the next 5 years. These priorities provide
      the future direction for NPD research and funding.

PMID- 22617786
TI  - Nursing professional development:  stories, tips, and techniques.

PMID- 22617787
TI  - Promoting your very best self.

PMID- 22617788
TI  - Assessment and planning for a dedicated education unit.
AB  - This pilot project describes the use of the Revised Professional Practice
      Environment scale to identify inpatient acute care units suitable for
      implementation of dedicated education units. Staff development professionals may
      use the suggested model to assess and plan phases of a dedicated education unit.

PMID- 22617790
TI  - Preceptors and new graduate nurse orientees: implications of psychological type
      compatibility.
AB  - The relationship between preceptor and new graduate nurse (NGN) orientee can be a
      critical factor in NGNs' satisfaction with choice of profession and place of
      employment. A research study was conducted with NGN orientees (n = 218) and
      preceptors (n = 159) to investigate characteristics of psychological type as
      determined by the Myers-Briggs Type Indicator. Preliminary descriptive data
      regarding participants' Myers-Briggs Type Indicator characteristics is presented,
      and suggestions are offered for working with orientees during orientation in both
      classroom sessions and clinical units.

PMID- 22617792
TI  - Dietary carbohydrate/lipid ratios affect stress, oxidative status and non
      specific immune responses of fingerling blunt snout bream, Megalobrama
      amblycephala.
AB  - This study aimed to evaluate the effects of dietary carbohydrate/lipid (CHO:L)
      ratios on stress, liver oxidative status and non-specific immune responses of
      fingerling blunt snout bream. Fish were fed six isonitrogenous and isoenergetic
      diets containing various CHO:L ratios for 10 weeks. After the feeding trial, fish
      were challenged by Aeromonas hydrophila and survival rate was recorded for the
      next 10 days. The lowest plasma cortisol, lactate, aspartate aminotransferase and
      alanine aminotransferase were all observed in fish fed a CHO:L ratio of 5.64.
      They were significantly (P < 0.05) lower than those of fish offered the lowest
      CHO:L ratio, but showed little difference (P > 0.05) with those of fish fed the
      highest CHO:L ratio. This also held true for liver catalase and glutathione
      peroxidase activities, whereas the opposite was true for liver reduced
      glutathione contents, plasma lysozyme and alternative complement (ACH50)
      activities. Contrary to leucocyte counts, plasma glucose levels, liver
      malondialdehyde contents, blood haemoglobin contents and erythrocyte numbers all
      increased significantly (P < 0.05) with decreasing dietary CHO:L ratios. The
      highest plasma total protein and globulin content both observed in fish fed a
      CHO:L ratio of 2.45 was significantly (P < 0.01) higher than that of fish offered
      the lowest CHO:L ratio, but showed no statistical difference (P > 0.05) with that
      of the other groups. After challenge, fish fed the lowest CHO:L ratio obtained
      significantly (P < 0.05) low survival rate. However, survival rate showed little
      difference (P > 0.05) as dietary CHO:L ratios ranged from 3.67 to 24.20. The
      results of this study indicated that high dietary lipid may cause metabolic
      stress of fingerling blunt snout bream, as might consequently lead to the
      elevated liver oxidation rates, impaired liver function, depressed immunity and
      reduced resistance to A. hydrophila infection of this species, whereas the
      opposite was true for carbohydrate enriched diets.

PMID- 22617791
TI  - MicroRNAs in erythroid and megakaryocytic differentiation and megakaryocyte
      erythroid progenitor lineage commitment.
AB  - MicroRNAs (miRNAs) are a class of small regulatory noncoding RNAs that modulate
      the expression of their target genes through either mRNA degradation or
      inhibition of protein translation. In recent years, miRNAs have been shown to be
      critical regulators of hematopoiesis and have important roles in the
      differentiation of specific lineages. Here, we summarize our current
      understanding of miRNAs involved in hematopoiesis with a focus on the role of
      miRNAs in regulating erythroid and megakaryocytic differentiation and
      megakaryocyte-erythroid progenitor lineage commitment.

PMID- 22617794
TI  - Toward a siRNA-containing nanoparticle targeted to breast cancer cells and the
      tumor microenvironment.
AB  - The present work aimed at designing a lipid-based nanocarrier for siRNA delivery
      toward two cell sub-populations within breast tumors, the cancer and the
      endothelial cells from angiogenic tumor blood vessels. To achieve such goal, the
      F3 peptide, which is specifically internalized by nucleolin overexpressed on both
      those sub-populations, was used as a targeting moiety. The developed F3-targeted
      stable nucleic acid lipid particles presented adequate features for systemic
      administration. In addition, the attachment of the F3 peptide onto the liposomal
      surface enabled an internalization by both cancer and endothelial cells from
      angiogenic blood vessels that was significantly higher than the one observed with
      non-cancer cells. Sequence-specific downregulation of enhanced green fluorescent
      protein (eGFP) in eGFP-overexpressing human cancer cell lines, both at the
      protein and mRNA levels, was further observed upon delivery of anti-eGFP siRNA by
      F3-targeted liposomes, in contrast with the non-targeted counterpart. This effect
      was highly dependent on the content of poly(ethylene glycol) (PEG), as evidenced
      by the co-localization studies between the siRNA and the lysosomes. Overall, the
      present work represents an important contribution toward a nanoparticle with
      multi-targeting capabilities in breast cancer, both at the cellular and molecular
      level.

PMID- 22617795
TI  - Is dialysis a reliable method for studying drug release from nanoparticulate
      systems?-A case study.
AB  - The kinetics of in vitro drug release from nanoparticulate systems is extensive,
      though uncritically, being studied by dialysis. Evaluating the actual relevance
      of dialysis data to drug release was the purpose of this study. Diclofenac- or
      ofloxacin-loaded chitosan nanoparticles crosslinked with tripolyphosphate were
      prepared and characterized. With each drug, dynamic dialysis was applied to
      nanoparticle dispersion, solution containing dissolved chitosan.HCl, and solution
      of plain drug. Drug kinetics in receiving phase (KRP), nanoparticle matrix (KNM)
      and nanoparticle dispersion medium (KDM) were determined. Release of each drug
      from nanoparticles was also assessed by ultracentrifugation. Although KRP data
      may be interpreted in terms of sustained release from nanoparticles, KNM and KDM
      data show that, with both drugs, the process was in fact controlled by permeation
      across dialysis membrane. Analysis of KRP data reveals a reversible interaction
      of diclofenac with dispersed nanoparticle surface, similar to the interaction of
      this drug with dissolved chitosan.HCl. No such interactions are noticed with
      ofloxacin. The results from the ultracentrifugation method agree with the above
      interpretation of dialysis data. This case study shows that dialysis data from a
      nanoparticle dispersion is not necessarily descriptive of sustained-release from
      nanoparticles, hence, if interpreted uncritically, it may be misleading.

PMID- 22617796
TI  - Polycistronic coexpression and nondenaturing purification of histone octamers.
AB  - Histone octamers are the basic building blocks of chromatin and are platforms for
      diverse genetic mechanisms. We report a simple method for preparing recombinant
      histone octamers by overexpressing all four histones from a single polycistronic
      vector followed by standard chromatography under native conditions. This approach
      reduces the time needed for the octamer preparation to a single day and should be
      applicable to making a variety of unmodified and modified histone octamers.

PMID- 22617797
TI  - beta-actin as a loading control for plasma-based Western blot analysis of major
      depressive disorder patients.
AB  - Western blot analysis is a commonly used technique for determining specific
      protein levels in clinical samples. For normalization of protein levels in
      Western blot, a suitable loading control is required. On account of its
      relatively high and constant expression, beta-actin has been widely employed in
      Western blot of cell cultures and tissue extracts. However, beta-actin's presence
      in human plasma and this protein's putative role as a plasma-based loading
      control for Western blot analysis remain unknown. In this study, an enzyme-linked
      immunosorbent assay was used to determine the concentration of beta-actin in
      human plasma, which is 6.29+/-0.54 ng/ml. In addition, the linearity of beta
      actin immunostaining and loaded protein amount was evaluated by Western blot, and
      a fine linearity (R2=0.974+/-0.012) was observed. Furthermore, the expression of
      plasma beta-actin in major depressive disorder subjects and healthy controls was
      compared. The data revealed no statistically significant difference between these
      two groups. Moreover, the total coefficient of variation for beta-actin
      expression in the two groups was 9.2+/-1.2%. These findings demonstrate that beta
      actin is present in human plasma and may possibly be used as a suitable loading
      control for plasma-based Western blot analysis in major depressive disorder.

PMID- 22617798
TI  - A universal fluorescent acceptor for high-performance liquid chromatography
      analysis of pro- and eukaryotic polysialyltransferases.
AB  - Polysialyltransferases (polySTs) play critical roles in diverse biological
      processes, including neural development, tumorigenesis, and bacterial
      pathogenesis. Although the bacterial enzymes are presumed to have evolved to
      provide molecular mimics of the host-specific polysialic acid, no analytical
      technique is currently available to facilitate a direct comparison of the
      bacterial and vertebrate enzymes. Here we describe a new fluorescent acceptor, a
      1,2-diamino-4,5-methylenedioxybenzene (DMB)-labeled trimer of alpha2,8-linked
      sialic acid (DMB-DP3), which primes both pro- and eukaryotic polySTs. High
      performance liquid chromatography separation and fluorescence detection (HPLC-FD)
      of reaction products enabled the sensitive and quantitative detection of polyST
      activity, even using cell lysates as enzyme source, and revealed product profiles
      characteristic of each enzyme. Single product resolution afforded by this assay
      system revealed mechanistic insights into a kinetic lag phase exhibited by the
      polyST from Neisseria meningitidis serogroup B during chain elongation. DMB-DP3
      is the first fluorescent acceptor shown to prime the mammalian polySTs. Moreover,
      product profiles obtained for the two murine polySTs provided direct biochemical
      evidence for enzymatic properties that had, until now, only been inferred from
      the analysis of biological samples. With DMB-DP3, we introduce a universal
      acceptor that provides an easy, fast, and reliable system for the comprehensive
      mechanistic and comparative analysis of polySTs.

PMID- 22617799
TI  - A quantitative assay to detect alpha-thalassemia deletions and triplications
      using multiplex nested real-time quantitative polymerase chain reaction.
AB  - Increasing evidence indicates that copy number variants (CNVs) have great
      relevance to common human diseases. In alpha-thalassemia, clinical phenotypes are
      related to genotypes, specifically copy number changes in the human alpha-globin
      gene cluster. Assays are available for high-throughput screening of unknown CNVs
      genome-wide and also for targeted CNV genotyping at loci associated with genetic
      disorders. Here we describe a universal quantitative approach based on nested
      real-time quantitative polymerase chain reaction for accurate determination of
      copy numbers at multiple particular gene loci. We used the alpha-globin gene as a
      model system, obtaining the reproducibility and sensitivity to analyze different
      gene copies and testing 95 DNA samples with 16 different known genotypes. Our
      results showed that this approach has high sensitivity and low standard
      deviations for correctly genotyping DNA samples containing different copy numbers
      of the alpha1 and alpha2 globin genes. Our method is rapid, simple, and reliable,
      and it could be used to simultaneously screen for alpha-thalassemia deletions or
      triplications. Moreover, it has potential as a versatile technology for the rapid
      genotyping of known CNVs in a targeted region.

PMID- 22617800
TI  - Tethering of proteins to RNAs using the bovine immunodeficiency virus-Tat peptide
      and BIV-TAR RNA.
AB  - To study the functions of RNA-binding proteins independent of their RNA-binding
      activity, tethering methods have been developed, based on the use of the RNA
      binding domain of a well-characterized RNA-binding protein and its target RNA.
      Two bacteriophage proteins have mainly been used as tethers: the MS2 coat protein
      and the lambda N protein. Here we report an alternative system using the Tat
      (trans-activator) peptide from the bovine immunodeficiency virus (BIV), which
      binds to BIV-TAR (trans-activation response) RNA. We demonstrate the usefulness
      of this system by applying it to the analysis of the TNRC6B protein, a component
      of the microRNA-induced silencing complex.

PMID- 22617801
TI  - Comparison of reverse transcription-quantitative polymerase chain reaction
      methods and platforms for single cell gene expression analysis.
AB  - Single cell gene expression analysis can provide insights into development and
      disease progression by profiling individual cellular responses as opposed to
      reporting the global average of a population. Reverse transcription-quantitative
      polymerase chain reaction (RT-qPCR) is the "gold standard" for the quantification
      of gene expression levels; however, the technical performance of kits and
      platforms aimed at single cell analysis has not been fully defined in terms of
      sensitivity and assay comparability. We compared three kits using purification
      columns (PicoPure) or direct lysis (CellsDirect and Cells-to-CT) combined with a
      one- or two-step RT-qPCR approach using dilutions of cells and RNA standards to
      the single cell level. Single cell-level messenger RNA (mRNA) analysis was
      possible using all three methods, although the precision, linearity, and effect
      of lysis buffer and cell background differed depending on the approach used. The
      impact of using a microfluidic qPCR platform versus a standard instrument was
      investigated for potential variability introduced by preamplification of template
      or scaling down of the qPCR to nanoliter volumes using laser-dissected single
      cell samples. The two approaches were found to be comparable. These studies show
      that accurate gene expression analysis is achievable at the single cell level and
      highlight the importance of well-validated experimental procedures for low-level
      mRNA analysis.

PMID- 22617802
TI  - Rostral ventromedial medulla modulates nociception and tonic immobility behavior
      through connections with the A7 catecholaminergic region.
AB  - Cholinergic stimulation of the rostral ventromedial medulla (RVM) produces
      antinociception and reduces the duration of tonic immobility (TI) behavior in
      guinea pigs. Previous studies indicated that cholinergic antinociception in the
      RVM is mediated through connections with the A7 catecholaminergic cell group
      (A7). In the current study, we tested the role of the A7 in both the
      antinociception and reduction of TI duration mediated by cholinergic stimulation
      of the RVM. In addition, we used biotinylated dextran amines (BDA) to evaluate
      the connections between the RVM and A7. The microinjection of the cholinergic
      agonist carbachol into the RVM produced antinociception and reduced TI behavior
      duration. These effects were blocked by prior administration of lidocaine to the
      A7. However, the microinjection of lidocaine into the A7 prior to saline
      injection into the RVM had no effect on either the nociceptive or TI responses.
      The microinjection of the neurotracer BDA into the RVM positively stained fibers
      and synaptic boutons in the A7, indicating that there are direct projections from
      the RVM to the A7. Taken together, our results indicate that the antinociception
      and reduction of TI behavior duration after cholinergic stimulation of the RVM
      depends on connections with the A7.

PMID- 22617803
TI  - Comparing physician and patient perceptions of quality in ambulatory care.
AB  - OBJECTIVE: If quality improvement interventions, value-based purchasing and/or
      certification are based on patient assessments, a common definition of quality
      should be shared by clinicians and patients. The study's objectives were to
      determine (i) how patients and clinicians define quality care, (ii) in what ways
      patients' and physicians' definitions differ and (iii) whether patients'
      definitions vary by ethnicity. DESIGN: We used the critical incident technique to
      interview participants about behaviors that resulted in office visits being
      considered either good or poor quality and compared the prevalence of different
      types of 'quality' behaviors reported to identify commonalities and differences.
      SETTING: Hawaii and Chicago. PARTICIPANTS: A total of 168 patients and 39
      clinicians. RESULTS: We developed a taxonomy, comprising 9 major categories and
      106 subcategories of behaviors responsible for quality visits. Almost all
      clinicians and patients agreed that clinical skill, rapport and health-related
      communication behaviors were key elements. Patients were more likely to report
      behaviors demonstrating thoroughness in routine examinations, spending enough
      time with them, engaging them and being treated with courtesy and respect as
      drivers of a quality office visit than were physicians. CONCLUSIONS: Increased
      clinician awareness of the behaviors that patients believe are the drivers of a
      quality office visit can help clinicians improve patients' experience of care and
      experience-based measures of quality.

PMID- 22617804
TI  - Are quality improvement methods a fashion for hospitals in Taiwan?
AB  - OBJECTIVE: This study reviews the rise and fall of the quality improvement (QI)
      methods implemented by hospitals in Taiwan, and examines the factors related to
      these methods. DESIGN: Cross-sectional, questionnaire-based survey. SETTING: One
      hundred and thirty-nine district teaching hospitals, regional hospitals and
      medical centers. PARTICIPANTS: Directors or the persons in charge of implementing
      QI methods. INTERVENTION: s) None. MAIN OUTCOME MEASURE: s) Breadth and depth of
      the 18 QI methods. RESULTS: Seventy-two hospitals responded to the survey, giving
      a response rate of 52%. In terms of breadth based on the hospitals' self
      reporting, the average number of QI methods adopted per hospital was 11.78
      (range: 7-17). More than 80% of the surveyed hospitals had implemented eight QI
      methods, and >50% had implemented five QI methods. The QI methods adopted by over
      80% of the surveyed hospitals had been implemented for a period of ~7 years. On
      the basis of the authors' classification, seven of the eight QI methods (except
      for QI team in total quality management) had an implementation depth of almost
      70% or higher in the surveyed hospitals. CONCLUSIONS: This study provides a
      snapshot of the QI methods implemented by hospitals in Taiwan. The results show
      that the average breadth of the QI methods adopted was 11.78; however, only 8.83
      were implemented deeply. The hospitals' accreditation level was associated with
      the breadth and depth of QI method implementation.

PMID- 22617805
TI  - A megavoltage scatter correction technique for cone-beam CT images acquired
      during VMAT delivery.
AB  - Kilovoltage cone-beam CT (kV CBCT) can be acquired during the delivery of
      volumetric modulated arc therapy (VMAT), in order to obtain an image of the
      patient during treatment. However, the quality of such CBCTs is degraded by
      megavoltage (MV) scatter from the treatment beam onto the imaging panel. The
      objective of this paper is to introduce a novel MV scatter correction method for
      simultaneous CBCT during VMAT, and to investigate its effectiveness when compared
      to other techniques. The correction requires the acquisition of a separate set of
      images taken during VMAT delivery, while the kV beam is off. These images--which
      contain only the MV scatter contribution on the imaging panel--are then used to
      correct the corresponding kV/MV projections. To test this method, CBCTs were
      taken of an image quality phantom during VMAT delivery and measurements of
      contrast to noise ratio were made. Additionally, the correction was applied to
      the datasets of three VMAT prostate patients, who also received simultaneous
      CBCTs. The clinical image quality was assessed using a validated scoring system,
      comparing standard CBCTs to the uncorrected simultaneous CBCTs and a variety of
      correction methods. Results show that the correction is able to recover some of
      the low and high-contrast signal to noise ratio lost due to MV scatter. From the
      patient study, the corrected CBCT scored significantly higher than the
      uncorrected images in terms of the ability to identify the boundary between the
      prostate and surrounding soft tissue. In summary, a simple MV scatter correction
      method has been developed and, using both phantom and patient data, is shown to
      improve the image quality of simultaneous CBCTs taken during VMAT delivery.

PMID- 22617806
TI  - Do-It-Yourself device for recovery of cryopreserved samples accidentally dropped
      into cryogenic storage tanks.
AB  - Liquid nitrogen is colorless, odorless, extremely cold (-196  degrees C) liquid
      kept under pressure. It is commonly used as a cryogenic fluid for long term
      storage of biological materials such as blood, cells and tissues (1,2). The
      cryogenic nature of liquid nitrogen, while ideal for sample preservation, can
      cause rapid freezing of live tissues on contact - known as 'cryogenic burn' (2),
      which may lead to severe frostbite in persons closely involved in storage and
      retrieval of samples from Dewars. Additionally, as liquid nitrogen evaporates it
      reduces the oxygen concentration in the air and might cause asphyxia, especially
      in confined spaces (2). In laboratories, biological samples are often stored in
      cryovials or cryoboxes stacked in stainless steel racks within the Dewar tanks
      (1). These storage racks are provided with a long shaft to prevent boxes from
      slipping out from the racks and into the bottom of Dewars during routine
      handling. All too often, however, boxes or vials with precious samples slip out
      and sink to the bottom of liquid nitrogen filled tank. In such cases, samples
      could be tediously retrieved after transferring the liquid nitrogen into a spare
      container or discarding it. The boxes and vials can then be relatively safely
      recovered from emptied Dewar. However, the cryogenic nature of liquid nitrogen
      and its expansion rate makes sunken sample retrieval hazardous. It is commonly
      recommended by Safety Offices that sample retrieval be never carried out by a
      single person. Another alternative is to use commercially available cool grabbers
      or tongs to pull out the vials (3). However, limited visibility within the dark
      liquid filled Dewars poses a major limitation in their use. In this article, we
      describe the construction of a Cryotolerant DIY retrieval device, which makes
      sample retrieval from Dewar containing cryogenic fluids both safe and easy.

PMID- 22617807
TI  - Fatigue in sarcoidosis:  incompletely understood, inadequately treated.

PMID- 22617808
TI  - Management of interstitial lung disease in elderly patients.
AB  - PURPOSE OF REVIEW: This review seeks to inform readers of evolving concepts of
      ageing-associated risks for developing interstitial lung disease (ILD) and
      current approaches to the diagnosis and management of ILD in elderly patients.
      RECENT FINDINGS: Various aspects of cellular and immune senescence have been
      identified that may explain the increased susceptibility of the elderly to
      developing fibrotic lung disease. New guidelines have been recently published
      concerning the diagnosis and management of idiopathic pulmonary fibrosis (IPF),
      which is highly prevalent in elderly patients. Nontransplant therapies that can
      have a significant impact on disease progression for patients with IPF have yet
      to be identified. Additionally, evidence is accumulating that abnormal
      gastroesophageal reflux and microaspiration may play a role in IPF pathogenesis.
      SUMMARY: High-resolution computed tomographic scanning of the thorax can play a
      key role in making a specific ILD diagnosis and be used to make a confident
      diagnosis of various forms of ILD, especially IPF, when combined with a
      consistent clinical presentation. Management of ILD in the elderly should be not
      only disease specific but potentially therapeutic, and supportive interventions
      should be tailored to each individual patient and not entail significant risk of
      adverse complications, especially for the frail elderly patient.

PMID- 22617809
TI  - Therapeutic approach of hepatic sarcoidosis.
AB  - PURPOSE OF REVIEW: Surveillance of hepatic involvement in sarcoidosis has not
      been standardized. Therefore, management of hepatic involvement is a clinical
      challenge. This review analyses published data on the pharmacological treatment
      of hepatic sarcoidosis. RECENT FINDINGS: Only 5-30% of patients with hepatic
      sarcoidosis display symptoms. Occasionally, it has a rapid progressive course
      with serious complications, stressing an appropriate and carefully timed
      therapeutic approach. Because symptomatic hepatic sarcoidosis is uncommon,
      therapeutic studies are scarce. Answers to the questions when to initiate which
      treatment are lacking. Case reports describe beneficial effects of prednisone and
      the augmentation of cytotoxic and anti-tumor necrotic factor-alpha (TNF-alpha)
      therapy. However, because of small sample sizes, no meaningful conclusions could
      be drawn. In symptomatic hepatic sarcoidosis patients, it is recommended to start
      to treat the sarcoidosis with prednisone, preceded by ursodeoxycholic acid when
      signs of cholestasis are present. In refractory cases or when prednisone weaning
      is impossible, cytotoxic drugs or anti-TNF-alpha therapy should be considered.
      SUMMARY: This review illustrates the importance of an appropriate therapeutic
      approach of sarcoidosis patients with hepatic involvement. It emphasizes the need
      for future studies to evaluate treatment options to avoid disease progression and
      hepatic complications.

PMID- 22617810
TI  - Thirty-day mortality rate in women with cancer and venous thromboembolism.
      Findings from the Registro Informatizado de la Enfermedad Trombo Embolica
      Registry.
AB  - PURPOSE OF REVIEW: Cancer patients with venous thromboembolism (VTE) are at
      increased risk of mortality. Estimating the risks for specific causes of death
      may help to weigh the risks and benefits of different therapeutic strategies in
      an individual patient. RECENT FINDINGS: In the Registro Informatizado de la
      Enfermedad Trombo Embolica Registry of 15 520 consecutive patients with VTE,
      cancer was present in 20% and was associated with a two-fold increase in the risk
      of fatal pulmonary embolism. In a subsequent study including 2474 women with
      cancer, 329 (13%) died during the first month. The incidence of fatal pulmonary
      embolism (n = 71) exceeded that of fatal bleeding (n = 22), except in women with
      cancer of the bladder or vulva. Then, we compared the mortality rate according to
      initial presentation in 3978 women with cancer and VTE, of whom 438 (11%) died
      during the first month. The risk of fatal bleeding was twice as high as the risk
      of fatal pulmonary embolism (12 vs. 5 deaths) in those with deep-vein thrombosis
      alone. SUMMARY: The higher risk of dying from bleeding than from pulmonary
      embolism in some women with cancer and VTE suggests that a less aggressive
      anticoagulant strategy might reduce fatal bleeding more than it would increase
      fatal pulmonary embolism during this period.

PMID- 22617811
TI  - Treatment of venous thromboembolism with dabigatran.
AB  - PURPOSE OF REVIEW: The first study on the treatment of venous thromboembolism
      (VTE) with dabigatran (RE-COVER) was published in 2009. Three additional phase
      III trials on acute VTE therapy and extended treatment were recently presented.
      This article reviews the data and, where applicable, compares them with other
      novel oral anticoagulants, particularly rivaroxaban, for which all phase III
      trials have been published. RECENT FINDINGS: A twin study to RE-COVER (RE-COVER
      II) confirmed that dabigatran is not inferior to warfarin regarding efficacy and
      confers a lower risk for clinically relevant bleeding in the treatment of acute
      VTE for 6 months. Two studies on the extended treatment of VTE with dabigatran
      showed that the results for efficacy and safety can be extrapolated to another 16
      months (mean) of treatment (RE-MEDY) and that dabigatran reduces the risk of
      recurrence by 90% compared with placebo (RE-SONATE). In the latter case, there is
      an increase of the risk for clinically relevant bleeding. SUMMARY: Dabigatran
      offers an alternative to warfarin for treatment of VTE without a need for
      coagulation monitoring or dose adjustments. Management of patients with VTE could
      thereby be simplified. Extended treatment might be considered more often for
      patients at higher risk of recurrence.

PMID- 22617812
TI  - Psychological stress in sarcoidosis.
AB  - PURPOSE OF REVIEW: Sarcoidosis is a chronic illness associated with emotional and
      physical consequences which impact on quality of life. Although the impact of
      fatigue is well understood, emotional impacts of sarcoidosis are less commonly
      recognized and addressed in routine clinical practice. The purpose of this review
      is to highlight that sarcoidosis can result in considerable psychological
      distress. RECENT FINDINGS: Not only is there a high prevalence of depressive
      symptoms in sarcoidosis, but clinical depressive and anxiety disorders are more
      common than seen in the general population. Patients with sarcoidosis have
      perceptions and beliefs about their disease that may impact on their willingness
      to engage in recommended therapies. They may also exhibit a disordered perception
      of their disease and a personality profile of neuroticism. Understanding the
      minimally important clinical difference in the Fatigue Assessment Scale (FAS) and
      validation of the Sarcoidosis Health Questionnaire (SHQ) across different
      populations supports the use of these tools in routine clinical practice and
      clinical trials. SUMMARY: Understanding the global impact of sarcoidosis is
      important for patients and clinicians, and use of validated instruments, such as
      the SHQ and FAS, allows for more comprehensive assessment of the disease and the
      impact of any interventions.

PMID- 22617813
TI  - Lung cancer screening:  making the transition from research to clinical practice.
AB  - PURPOSE OF REVIEW: The purpose of this review is to examine the literature on
      lung cancer screening with an emphasis on the prevalence of cancer in screen
      detected nodules. On the basis of the evidence, we will then develop a practical
      approach to screen-detected lung nodules. RECENT FINDINGS: The first large
      randomized controlled trial using low-dose computed tomography (LDCT) found that
      persons undergoing three annual screening examinations with LDCT had a 20%
      relative reduction in lung cancer mortality as compared with those screened with
      annual chest X-rays. The probability of cancer in screen-detected nodules depends
      on their size and whether the nodules are detected on prevalence or incidence
      screens. The probability of cancer in screen-detected nodules ranges from 2.4 to
      5.2%. Management strategies for screen-detected nodules that have been used
      successfully include careful observation using serial CT imaging, CT-guided fine
      needle biopsy, and surgery in carefully selected cases. The most frequently used
      strategies involve serial CT imaging and CT-guided biopsy for larger nodules and
      those that demonstrate growth on follow-up. SUMMARY: There is now evidence that
      LDCT in carefully selected high-risk populations can lead to better outcomes but
      the cost effectiveness of mass screening with LDCT is still unknown. Only
      patients at high risk for cancer should be screened.

PMID- 22617814
TI  - Asbestos-related pleural disease.
AB  - PURPOSE OF REVIEW: Asbestos exposure is the cause of significant pleural disease 
      both benign and malignant. Although there is increased awareness, individuals
      continue to be exposed, and we will continue to see its sequelae for years to
      come because of the delay between exposure and disease manifestation. Asbestos
      related pleural disease includes pleural plaques, diffuse pleural thickening,
      benign asbestos-related pleural effusions (BAPEs), and malignant pleural
      mesothelioma (MPM). RECENT FINDINGS: Several recent studies are highlighted
      throughout this review, including a comparative analysis of diagnostic imaging
      modalities for identifying and characterizing pleural plaques, the effect of
      pleural plaques on lung volumes and flows, and how pain is a relatively common
      feature in patients with pleural plaques. Advances in the treatment of MPM are
      limited, but a recent publication highlights the increased morbidity associated
      with surgical debulking procedures and questions the benefit of these procedures.
      SUMMARY: Asbestos-related pleural disease will continue to present a significant
      burden of illness. Recent publications have suggested potential treatment benefit
      and point to areas that would require further investigation.

PMID- 22617815
TI  - Functional studies and rare variant screening of SLC1A1/EAAC1 in males with
      obsessive-compulsive disorder.
AB  - Several studies have found that the neuronal glutamate transporter gene
      SLC1A1/EAAC1 is associated with obsessive-compulsive disorder (OCD), with a
      stronger association in males. Previous studies have primarily focused on common
      single-nucleotide polymorphisms, rather than rare functional variants that are
      likely to have larger effects. We screened 184 males with OCD for rare variation
      in SLC1A1 exons; however, no new coding variation was found. When combined with
      previous screens, only one SLC1A1 amino acid variant has been detected among the
      841 individuals screened, which is less than for other neurotransmitter
      transporter genes (P=0.0001). We characterized the function of the one SLC1A1
      missense variant reported previously in OCD, Thr164Ala, and found that the Ala164
      allele leads to decreased Vmax and Km (P<0.0001) in transfected human embryonic
      kidney cells. Further work will be necessary to understand the impact of this
      rare SLC1A1/EAAC1 Ala164 variant on neuronal function and circuitry relevant to
      OCD.

PMID- 22617816
TI  - Prevalence of limb muscle dysfunction in patients with chronic obstructive
      pulmonary disease admitted to a pulmonary rehabilitation centre.
AB  - OBJECTIVE: Assessment of needle electromyography (nEMG) may complement previous
      data on limb muscle dysfunction (LMD) in patients with chronic obstructive
      pulmonary disease (COPD). We attempted to quantify the prevalence of LMD and
      assess its impact on clinical outcomes in patients admitted to a rehabilitation
      programme. METHODS: One hundred and thirty-two clinically stable patients were
      consecutively enrolled. They underwent spirometry and the following primary
      outcomes were evaluated: St. George respiratory questionnaire (SGRQ), functional
      independence measure (FIM) questionnaire and a 6-min walking test (6MWT). One
      hundred and fourteen patients underwent nEMG. The frequency of LMD was related to
      COPD stage and chronic dyspnoea. RESULTS: nEMG detected myopathic signs in 36.8%
      of the patients. LMD was found even in early stages of COPD. FIM and 6MWT were
      significantly lower, and SGRQ tended to be higher at each COPD stage in patients
      with LMD. However, the 6MWT rate of decay across the COPD stages was similar in
      patients with and without LMD. CONCLUSIONS: LMD might not be restricted to
      patients with severe airway obstruction and regardless of COPD stage, contributes
      to functional limitation of these patients. SIGNIFICANCE: The putative role of
      LMD in motor limitations indicates the need to assess it early onto better
      organise a specific training programme as part of general pulmonary
      rehabilitation in COPD patients.

PMID- 22617818
TI  - To the editor.

PMID- 22617817
TI  - Vascular development during distraction osteogenesis proceeds by sequential
      intramuscular arteriogenesis followed by intraosteal angiogenesis.
AB  - Vascular formation is intimately associated with bone formation during
      distraction osteogenesis (DO). While prior studies on this association have
      focused on vascular formation locally within the regenerate, we hypothesized that
      this vascular formation, as well as the resulting osteogenesis, relies heavily on
      the response of the vascular network in surrounding muscular compartments. To
      test this hypothesis, the spatiotemporal sequence of vascular formation was
      assessed in both muscular and osseous compartments in a murine model of DO and
      was compared to the progression of osteogenesis. Micro-computed tomography (MUCT)
      scans were performed sequentially, before and after demineralization, on
      specimens containing contrast-enhanced vascular casts. Image registration and
      subtraction procedures were developed to examine the co-related, spatiotemporal
      patterns of vascular and osseous tissue formation. Immunohistochemistry was used
      to assess the contributory roles of arteriogenesis (formation of large vessels)
      and angiogenesis (formation of small vessels) to overall vessel formation. Mean
      vessel thickness showed an increasing trend during the period of active
      distraction (p=0.068), whereas vessel volume showed maximal increases during the
      consolidation period (p=0.009). The volume of mineralized tissue in the
      regenerate increased over time (p<0.039), was correlated with vessel volume
      (r=0.59; p=0.025), and occurred primarily during consolidation.
      Immunohistological data suggested that: 1) the period of active distraction was
      characterized primarily by arteriogenesis in the surrounding muscle; 2) during
      consolidation, angiogenesis predominated in the intraosteal region; and 3) vessel
      formation proceeded from the surrounding muscle into the regenerate. These data
      show that formation of vascular tissue occurs in both muscular and osseous
      compartments during DO and that periods of intense osteogenesis are concurrent
      with those of angiogenesis. The results further suggest the presence of
      morphogenetic factors that coordinate the development of vascular tissues from
      the intramuscular compartment into the regions of osseous regeneration.

PMID- 22617820
TI  - Efficient, divergent synthesis of cryptophycin unit A analogues.
AB  - A flexible and divergent synthesis of cryptophycin unit A analogues is described.
      This method relies on iridium-catalysed stereo- and enantioselective crotylation
      and chemoselective one-pot oxidative olefination to access common intermediate .
      Heck, cross metathesis, and Suzuki-Miyaura reactions are illustrated for the
      generation of methyl ester unit A analogues .

PMID- 22617821
TI  - Epstein-Barr virus cause of multiple sclerosis.
AB  - PURPOSE OF REVIEW: The cause of multiple sclerosis (MS) has eluded medical
      science for over a century. Pierre Marie speculated that MS is an infectious
      disease and this paradigm has had a prominent place in the discussion. A number
      of candidate pathogens have been proposed, but most have not survived scrutiny.
      In this review, we summarize the evidence that MS is caused by Epstein-Barr virus
      (EBV), which has been a prominent candidate for several decades. Although there
      is much suggestive evidence that EBV is involved in the pathogenesis of MS, the
      precise effect of EBV is still unclear. RECENT FINDINGS: EBV is more common in MS
      patients than in controls. A history of infectious mononucleosis, and high
      baseline EBV antibody titers are risk factors for MS. More controversial are
      findings of changes in the reactivity of the T-cell repertoire, presence of EBV
      antibodies in the cerebrospinal fluid, and presence of EBV in meningeal lymphoid
      follicles and perivenular infiltrates in the white matter. SUMMARY: The
      contribution of EBV to the cause of MS is not yet established, but a relationship
      is clearly present.

PMID- 22617822
TI  - Role of Helicobacter pylori infection in autoimmune diseases.
AB  - PURPOSE OF REVIEW: The etiology of most autoimmune diseases remains elusive.
      Prevailing evidence suggests an environmental trigger in a genetically
      susceptible individual. Helicobacter pylori (H. pylori) have managed to survive
      in a hostile environment in their host for long period and have evaded
      eradication by the immune system. Its chronic interaction with the immune system
      and the ubiquitous presence worldwide makes H. pylori an ideal candidate to study
      as a trigger of autoimmune phenomena. In this review, we would present data
      regarding the interplay between H. pylori and various components of the immune
      system and its association with various autoimmune diseases. RECENT FINDINGS:
      Strong associations of H. pylori with some autoimmune diseases such as immune
      thrombocytopenia have been found; but most other autoimmune disease studies have
      revealed conflicting data. The chronic survival of H. pylori in humans is
      possible because of an overall downregulation of the body's immune response. In
      addition to this overall effect on the immune system, there are clinical and
      epidemiological data suggestive of H. pylori infection having a protective role
      in some autoimmune diseases. SUMMARY: Based on our review H. pylori status should
      be checked and treated only in certain autoimmune diseases such as ITP. For the
      majority of the autoimmune diseases, the role of H. pylori remains controversial
      signifying need for further research.

PMID- 22617823
TI  - Infections and vaccines in the etiology of antiphospholipid syndrome.
AB  - PURPOSE OF REVIEW: To present scientific evidence supporting the infectious
      origin for the antiphospholipid syndrome (APS) by molecular mimicry between
      pathogens, infection and vaccination with beta2-glycoprotein I (beta2-GPI)
      molecule. RECENT FINDINGS: APS is characterized by the presence of pathogenic
      autoantibodies against beta2-GPI. The infection etiology of APS was well
      established. Likewise, a link between vaccination such as tetanus toxoid may
      trigger antibodies targeting tetanus toxoid and beta2-GPI, due to molecular
      mimicry between the two molecules. During the years, the pathogenic potential of
      anti-tetanus toxoid antibodies cross reactive with beta2-GPI were found to be
      pathogenic in animal models, inducing experimental APS. SUMMARY: Accumulated
      evidence supports that the presence of anti-beta2-GPI antibodies is associated
      with a history of infections and the main mechanism to explain this correlation
      is molecular mimicry. The relationship between tetanus toxoid vaccination and APS
      reveals a novel view on the autoimmune/autoinflammatory syndrome induced by
      adjuvants (ASIA).

PMID- 22617824
TI  - Peripheral manifestations in spondyloarthritis:  relevance for diagnosis,
      classification and follow-up.
AB  - PURPOSE OF REVIEW: The field of spondyloarthritis (SpA) has evolved enormously
      over the last few years, starting with the advent of biological therapies at the
      end of the previous millenium. A lot of work has been done to construct valid
      outcome measures and treatment guidelines based upon the results of pivotal
      studies with Tumor necrosis factor (TNF)-blocking agents. Most of these trials
      were performed in well described populations, such as patients suffering from
      ankylosing spondylitis (AS) or psoriatic arthritis. RECENT FINDINGS: Over recent
      years a reappraisal has been done with regard to considering again the full
      spectrum of diseases belonging to the SpA concept, especially in early disease
      stages. This effort culminated in the construction of new classification criteria
      for axial and peripheral SpA. Around the same time, a number of patient
      registries were set up, allowing the follow-up of patients in order to study the
      natural evolution of patients classified early. The first data from these cohorts
      provide interesting information on peripheral joint manifestations such as
      arthritis, enthesitis or dactylitis. Recognition and monitoring of these
      manifestations are essential for clinicians in order to provide comprehensive
      patient care. SUMMARY: There is a growing interest in the field of SpA to move
      from rather restricted and longstanding diseases such as AS to a more
      comprehensive view, encompassing not only inflammatory back pain, but also
      peripheral arthritis and enthesitis, as well as extra-articular manifestations.
      The new classification criteria and guidelines for follow-up are applied now in a
      number of prospective patient registries, and provide us with valuable
      information on the early disease stages of SpA.

PMID- 22617825
TI  - Role of ultrasound in the diagnostic work-up of spondyloarthritis.
AB  - PURPOSE OF REVIEW: The technological progress of ultrasound has permitted an
      accurate visualization of inflammation and structural changes of superficial
      tissues. This review focusses on the advantages and current limitations of
      ultrasound for visualizing enthesitis in the context of spondyloarthritis (SpA).
      RECENT FINDINGS: Several studies have described the ultrasound features of
      enthesitis in SpA, revealing the high frequency of clinically asymptomatic
      findings and the added value of ultrasound, coupled with power Doppler, for
      diagnosing SpA. Encouraging reports on high agreement between observers and the
      sensitivity to change the technique were recently published. However, a number of
      essential issues are still largely unexplored. A correct and consensual
      definition of enthesitis is still missing, and the published data are sometimes
      contradictory on the diagnostic capability of ultrasound because of the different
      definitions of enthesitis used. The quality of the Doppler equipment still plays
      a crucial role for visualizing inflammation, and the validity of the technique
      for prognostic purposes needs to be addressed. SUMMARY: Power Doppler ultrasound
      is a very promising tool, but still needs validation. Future standardized studies
      will permit ultrasound to become a reference method for diagnosis and monitoring
      SpA peripheral enthesitis in clinical practice and research.

PMID- 22617827
TI  - Lupus neutrophils:  'NET' gain in understanding lupus pathogenesis.
AB  - PURPOSE OF REVIEW: Historically, researchers have focused on the role of adaptive
      immunity in lupus pathogenesis; recently, however, there has been renewed
      interest in the contributions of a prototypical innate immune cell - the
      neutrophil. RECENT FINDINGS: Neutrophil extracellular traps (NETs) are released
      via a novel form of cell death called NETosis. NETs, consisting of a chromatin
      meshwork decorated with antimicrobial peptides, play an important role in the
      innate response to microbial infections. Some lupus patients do not clear NETs
      normally, a phenotype that correlates with disease activity. Further, lupus
      neutrophils - and, in particular, an aberrant subset called low-density
      granulocytes - have an increased propensity to undergo NETosis. Both interferon
      alpha (IFNalpha) and immune complexes are potential triggers of enhanced NETosis
      in lupus patients. SUMMARY: NETs are a potent stimulus for IFNalpha release by
      plasmacytoid dendritic cells, and, as such, may play an important role in
      propagation of the lupus phenotype. NETs can also directly damage tissues -
      including the endothelium - with implications for lupus nephritis and accelerated
      atherosclerosis. Whether aberrant NETosis is sufficient to trigger systemic lupus
      erythematosus, and whether inhibition of NETosis can ameliorate clinical
      manifestations of lupus, are open questions, and will be exciting topics of
      future research.

PMID- 22617826
TI  - Streptococcus and rheumatic fever.
AB  - PURPOSE OF REVIEW: To give an overview of the current hypotheses of the
      pathogenesis of rheumatic fever and group A streptococcal autoimmune sequelae of
      the heart valve and brain. RECENT FINDINGS: Human monoclonal antibodies (mAbs)
      derived from rheumatic heart disease have provided evidence for crossreactive
      autoantibodies that target the dominant group A streptococcal epitope of the
      group A carbohydrate, N-acetyl-beta-D-glucosamine (GlcNAc), and heart valve
      endothelium, laminin and laminar basement membrane. T cells in peripheral blood
      and in rheumatic heart valves revealed the presence of T cells crossreactive with
      streptococcal M protein and cardiac myosin. For initiation of disease, evidence
      suggests a two-hit hypothesis for antibody attack on the valve endothelium with
      subsequent extravasation of T cells through activated endothelium into the valve
      to form granulomatous lesions and Aschoff bodies. Autoantibodies against the
      group A streptococcal carbohydrate epitope GlcNAc and cardiac myosin and its
      peptides appear during progression of rheumatic heart disease. However,
      autoantibodies against collagen that are not crossreactive may form because of
      the release of collagen from damaged valve or to responses to collagen bound in
      vitro by certain serotypes of streptococci. In Sydenham chorea, human mAbs
      derived from disease target the group A carbohydrate epitope GlcNAc and
      gangliosides and dopamine receptors found on the surface of neuronal cells in the
      brain. Human mAbs and autoantibodies in Sydenham chorea were found to signal
      neuronal cells and activate calcium calmodulin-dependent protein kinase II
      (CaMKII) in neuronal cells and recognize the intracellular protein biomarker
      tubulin. SUMMARY: To summarize, pathogenic mechanisms of crossreactive
      autoantibodies which target the valve in rheumatic heart disease and the neuronal
      cell in Sydenham chorea share a common streptococcal epitope GlcNAc and target
      intracellular biomarkers of disease including cardiac myosin in the myocardium
      and tubulin, a protein abundant in the brain. However, intracellular antigens are
      not believed to be the basis for disease. The theme of molecular mimicry in
      streptococcal autoimmune sequelae is the recognition of targeted intracellular
      biomarker antigens such as cardiac myosin and brain tubulin, while targeting
      extracellular membrane antigens such as laminin on the valve surface endothelium
      or lysoganglioside and dopamine receptors in the brain. Antibody binding to these
      cell surface antigens may lead to valve damage in rheumatic heart disease or
      neuropsychiatric behaviors and involuntary movements in Sydenham chorea.

PMID- 22617828
TI  - Mechanisms mediating parallel action monitoring in fronto-striatal circuits.
AB  - Flexible response adaptation and the control of conflicting information play a
      pivotal role in daily life. Yet, little is known about the neuronal mechanisms
      mediating parallel control of these processes. We examined these mechanisms using
      a multi-methodological approach that integrated data from event-related
      potentials (ERPs) with structural MRI data and source localisation using sLORETA.
      Moreover, we calculated evoked wavelet oscillations. We applied this multi
      methodological approach in healthy subjects and patients in a prodromal phase of
      a major basal ganglia disorder (i.e., Huntington's disease), to directly focus on
      fronto-striatal networks. Behavioural data indicated, especially the parallel
      execution of conflict monitoring and flexible response adaptation was modulated
      across the examined cohorts. When both processes do not co-incide a high
      integrity of fronto-striatal loops seems to be dispensable. The
      neurophysiological data suggests that conflict monitoring (reflected by the N2
      ERP) and working memory processes (reflected by the P3 ERP) differentially
      contribute to this pattern of results. Flexible response adaptation under the
      constraint of high conflict processing affected the N2 and P3 ERP, as well as
      their delta frequency band oscillations. Yet, modulatory effects were strongest
      for the N2 ERP and evoked wavelet oscillations in this time range. The N2 ERPs
      were localized in the anterior cingulate cortex (BA32, BA24). Modulations of the
      P3 ERP were localized in parietal areas (BA7). In addition, MRI-determined
      caudate head volume predicted modulations in conflict monitoring, but not working
      memory processes. The results show how parallel conflict monitoring and flexible
      adaptation of action is mediated via fronto-striatal networks. While both,
      response monitoring and working memory processes seem to play a role, especially
      response selection processes and ACC-basal ganglia networks seem to be the
      driving force in mediating parallel conflict monitoring and flexible adaptation
      of actions.

PMID- 22617829
TI  - An anterior-posterior gradient of cognitive control within the dorsomedial
      striatum.
AB  - Lateral prefrontal cortex and basal ganglia work together to mediate working
      memory and top-down regulation of cognition. This circuit regulates the balance
      and interactions between automatic and high-order control responses. Using ultra
      high-field high-resolution functional magnetic resonance imaging (7T-fMRI), the
      present study examined the role of subcortical structures in cognitive control
      during language processing. Participants were asked to judge the grammaticality
      of unambiguous, ungrammatical and ambiguous sentences. Grammatical unambiguous
      sentences should elicit an automatic response, while ambiguous and ungrammatical
      sentences should conflict with the automatic response and, hence, require a high
      order control response. Within the control response domain, ambiguity and
      ungrammaticality represent two different dimensions of conflict resolution, while
      for a temporarily ambiguous sentence a correct interpretation is available, that
      is not the case for ungrammatical sentences. Our results reveal an anterior
      posterior axis in the dorsomedial striatum with more rostral regions supporting
      higher levels of cognitive processing. This functional architecture mirrors the
      rostrocaudal hierarchical organization evidenced within the lateral prefrontal
      cortex.

PMID- 22617830
TI  - Quantitative analysis of rhegmatogenous retinal detachment associated with
      choroidal detachment in Chinese using UBM.
AB  - PURPOSE: To investigate the characteristics of rhegmatogenous retinal detachment
      associated with choroidal detachment (RRDCD) in a Chinese population by using
      ultrasound biomicroscope (UBM). METHODS: A random prospective study was used to
      assess 1,389 patients (1,408 eyes) with rhegmatogenous retinal detachment.
      Comprehensive standardized ophthalmic examinations included intraocular pressure
      (IOP) by Goldmann applanation tonometer and the entire ocular fundus by Goldmann
      three-mirror lens, B-type ultrasound, and UBM. RESULTS: A total of 1,389 patients
      with rhegmatogenous retinal detachment participated in the study, including 906
      men and 483 women. Two hundred and sixty-three eyes (18.79%) had RRDCD and the
      age of patients ranged from 9 to 82 years (median, 50.8 +/- 17.7 years). Patients
      with high myopia (-6.00 diopters or more) represented 31.94% and more frequently
      experienced low intraocular pressure and multiple retinal breaks. In 263 RRDCD
      eyes, the results of UBM showed that ranges of choroidal detachment (CD) were <1
      quadrant in 9 (3.42%) eyes, from 1 to 2 quadrants in 37 (14.07%) eyes, from 2 to
      3 quadrants in 13 (4.94%) eyes, and from 3 to 4 quadrants in 204 (77.57%) eyes.
      ultrasound biomicroscope also showed that the angular ranges of CD were between
      3.31 degrees  and 45.65 degrees  (mean, 15.98 +/- 9.29 degrees ). In addition,
      UBM showed the mean values of CD angle for the superior (15.42 +/- 9.40 degrees
      ), nasal (14.08 +/- 8.66 degrees ), inferior (15.03 +/- 9.05 degrees ), and
      temporal (15.96 +/- 9.22 degrees ) sides. No statistically significant
      differences were found among any of these comparisons (F value = 2.011, P >
      0.05). CONCLUSION: Retinal detachment associated with CD occurs more frequently
      in older people or in patients with high myopia, who usually present with low
      intraocular pressure and multiple retinal breaks. UBM examination can reduce
      false-negative rate of RRDCD, determine CD degree quantitatively, and guide
      classification and treatment. UBM combined with B ultrasound testing can provide
      a precise diagnosis of rhegmatogenous retinal detachment degree and may have
      important clinical significance for preoperative diagnosis of anterior
      proliferative vitreoretinopathy and determining operative strategy and
      postoperative prognosis.

PMID- 22617831
TI  - Comparison of intraoperative complications of phacoemulsification between
      sequential and combined procedures of pars plana vitrectomy and cataract surgery.
AB  - PURPOSE: To compare intraoperative complications during phacoemulsification
      between sequential and combined procedures of vitrectomy and cataract surgery.
      METHODS: We retrospectively reviewed the medical records of 54 patients who
      underwent cataract surgery in a previously vitrectomized eye (sequential group)
      and 311 patients who underwent combined vitrectomy and cataract surgery (combined
      group). Primary outcome measures were intraoperative complications during
      phacoemulsification. Secondary measures were preoperative and intraoperative
      cataract gradings. RESULTS: The most common complication during
      phacoemulsification was posterior capsule rupture. The rate of posterior capsule
      rupture was higher in the sequential group (6 eyes, 11.4%) than in the combined
      group (14 eyes 4.5%, P = 0.049). Preoperative lens density (nuclear color and
      posterior subcapsular scores) was higher in the sequential group (P < 0.001).
      Intraoperative nuclear grading was higher compared with the preoperative one in
      the sequential group, but the two gradings did not differ in the combined group.
      CONCLUSION: Phacoemulsification in a vitrectomized eye is associated with a
      higher rate of posterior capsule rupture than the one in combined vitrectomy.
      These results may have been caused by hard nucleus cataract in a vitrectomized
      eye.

PMID- 22617832
TI  - Morphologic characteristics of chronic macular hole on optical coherence
      tomography.
AB  - PURPOSE: To investigate the morphologic characteristics of chronic macular holes
      (MHs) using optical coherence tomography. METHODS: We retrospectively reviewed
      optical coherence tomographic images of consecutive patients who had been
      diagnosed with MH. Chronic MH was defined as MH that was observed without being
      surgically treated for at least 1 year. Optical coherence tomographic parameters
      were compared between chronic and acute MH. RESULTS: Thirteen eyes of 13 patients
      were classified as chronic MH, and 67 eyes of 67 patients were classified as
      controls. While the basal hole diameter of chronic MH was not different from that
      of controls (P = 0.146), the minimum hole diameter (781.8 MUm) of chronic MH was
      larger than that of controls (448.4 MUm; P < 0.001). The hole height and MH index
      were smaller in the chronic MH group (380.6 MUm; 0.31) than in control group
      (469.9 MUm, 0.53; P = 0.033, P = 0.003). Intraretinal fluid was less frequently
      observed in chronic MH than in controls (P < 0.001). Retinal pigment epithelial
      atrophy was only observed in chronic MH. CONCLUSION: Chronic MH has features
      distinct from those of acute symptomatic MH on optical coherence tomography.
      These findings provide useful insight for the differentiation of chronic MH from
      acute MH.

PMID- 22617833
TI  - Cytokine concentration in aqueous humor of eyes with diabetic macular edema.
AB  - PURPOSE: To measure cytokine concentrations in aqueous humor of eyes with diffuse
      diabetic macular edema. METHODS: The interventional clinical comparative study
      included a study group of 23 patients with diffuse diabetic macular edema and a
      control group of 22 patients undergoing cataract surgery. Cytokine concentrations
      were measured in aqueous humor samples using a Luminex xMAP suspension array
      technology. RESULTS: In the study group as compared with the control group,
      significantly higher concentrations were measured for epidermal growth factor (P
      < 0.001), human growth factor (P < 0.001), intercellular adhesion molecule-1
      (ICAM-1; P < 0.001), interleukin (IL)-1a2 (P = 0.04), IL-6 (P = 0.001), IL-8 (P <
      0.001), interferon gamma-induced protein (P = 0.004), monocyte chemoattractant
      protein-1 (P < 0.001), monokine induced by interferon gamma (P < 0.001), matrix
      metalloproteinase 1 (P = 0.02), matrix metalloproteinase 9 (P < 0.001),
      plasminogen activator inhibitor 1 (P < 0.001), placenta growth factor (P <
      0.001), tissue growth factor beta (P = 0.003), vascular cell adhesion molecule (P
      < 0.001), and vascular endothelial growth factor (P < 0.001). Retinal macula
      thickness was significantly associated with the concentrations of the epidermal
      growth factor (P = 0.005; rho = 0.45), ICAM-1 (P < 0.001; rho = 0.65), IL-3 (P =
      0.002; rho = 0.48), IL-6 (P = 0.003; rho = 0.47), IL-8 (P < 0.001; rho = 0.71),
      monocyte chemoattractant protein-1 (P = 0.001; rho = 0.53), monokine induced by
      interferon gamma (P < 0.001; rho = 0.57), matrix metalloproteinase 9 (P < 0.001;
      rho = 0.61), tissue growth factor beta (P = 0.01; rho = 0.42), placenta growth
      factor (P = 0.004; rho = 0.46), vascular cell adhesion molecule (P = 0.006; rho =
      0.44), and vascular endothelial growth factor (P = 0.01; rho = 0.42). In
      multivariate analysis, macular thickness remained to be significantly associated
      with the concentration of ICAM-1 (P = 0.03; r = 0.30). Vascular endothelial
      growth factor concentrations were correlated with concentration of placenta
      growth factor (P < 0.001; rho = 0.78), plasminogen activator inhibitor 1 (P =
      0.001; rho = 0.54), ICAM-1 (P < 0.001; rho = 0.47), monokine induced by
      interferon gamma (P = 0.004; rho = 0.44), monocyte chemoattractant protein-1 (P =
      0.003; rho = 0.43), vascular cell adhesion molecule (P = 0.01; rho = 0.38), IL-6
      (P = 0.02; rho = 0.35), IL-8 (P = 0.02; rho = 0.37), epidermal growth factor (P =
      0.01; rho = 0.39), and macrophage migration inhibitory factor (P = 0.01; rho =
      0.37). CONCLUSION: Numerous cytokines are associated with the presence and the
      amount of diabetic macular edema. Among these cytokines, ICAM-1 was the most
      significantly associated with the disease parameters.

PMID- 22617834
TI  - Lessons learned and applied: what the 20th century vaccine experience can teach
      us about vaccines in the 21st century.
AB  - Most vaccines available in the United States have been incorporated into
      vaccination schedules for infants and young children, age groups particularly at
      risk of contracting infectious diseases. High universal vaccination coverage is
      responsible for substantially reducing or nearly eliminating many of the diseases
      that once killed thousands of children each year in the US. Despite the success
      of infant vaccinations, periods of low vaccination coverage and the limited
      immunogenicity and duration of protection of certain vaccines have resulted in
      sporadic outbreaks, allowing some diseases to spread in communities. These
      challenges suggest that expanded vaccination coverage to younger infants and
      adolescents, and more immunogenic vaccines, may be needed in some instances. This
      review focuses on the importance of infant immunization and explores the
      successes and challenges of current early childhood vaccination programs and how
      these lessons may be applied to other invasive diseases, such as meningococcal
      disease.

PMID- 22617837
TI  - Temporal and spatial interplay of microbiota and intestinal mucosa drive
      establishment of immune homeostasis in conventionalized mice.
AB  - During colonization of germfree mice with the total fecal microbial community of
      their conventionally born and raised siblings (conventionalization), the
      intestinal mucosal immune system initiates and maintains a balanced immune
      response. However, the genetic regulation of these balanced, appropriate
      responses to the microbiota is obscure. Here, combined analysis of germfree and
      conventionalized mice revealed that the major molecular responses could be
      detected initiating at day 4 post conventionalization, with a strong induction of
      innate immune functions followed by stimulation of adaptive immune responses and
      development and expansion of adaptive immune cells at later stages of
      conventionalization. This study provides a comprehensive overview of mouse
      developmental and immune-related cellular pathways and processes that were co
      mediated by the commensal microbiota and suggests which mechanisms were involved
      in this reprogramming. The dynamic, region-dependent mucosal responses to the
      colonizing microbiota revealed potential transcriptional signatures for the
      control of intestinal homeostasis in healthy mice, which may help to decipher the
      genetic basis of pathway dysregulation in human intestinal inflammatory diseases.

PMID- 22617836
TI  - The Src kinase Yes is activated in pancreatic acinar cells by gastrointestinal
      hormones/neurotransmitters, but not pancreatic growth factors, which stimulate
      its association with numerous other signaling molecules.
AB  - For growth factors, cytokines, G-protein-coupled receptors and numerous other
      stimuli, the Src Family of kinases (SFK) play a central signaling role. SFKs also
      play an important role in pancreatic acinar cell function including metabolism,
      secretion, endocytosis, growth and cytoskeletal integrity, although the specific
      SFKs involved are not fully known. In the present study we used specific
      antibodies for the SFK, Yes, to determine its presence, activation by pancreatic
      secretagogues or growth factors, and interaction with cellular signaling cascades
      mediated by CCK in which Yes participates in to cause acinar cell responses. Yes
      was identified in acini and secretagogues known to activate phospholipase C (PLC)
      [CCK, carbachol, bombesin] as well as post-receptor stimulants activating PKC
      [TPA] or mobilizing cellular calcium [thapsigargin/calcium ionophore (A23187)]
      each activated Yes. Secretin, which activates adenylate cyclase did not stimulate
      Yes, nor did pancreatic growth factors. CCK activation of Yes required both high-
      and low-affinity CCK(1)-receptor states. TPA-/CCK-stimulated Yes activation was
      completely inhibited by thapsigargin and the PKC inhibitor, GF109203X. CCK/TPA
      stimulated the association of Yes with focal adhesion kinases (Pyk2, FAK) and its
      autophosphorylated forms (pY397FAK, pY402Pyk2). Moreover, CCK/TPA stimulated Yes
      interacted with a number of other signaling proteins, including Shc, PKD,
      p130(Cas), PI3K and PTEN. This study demonstrates that in rat pancreatic acini,
      the SFK member Yes is expressed and activated by CCK and other gastrointestinal
      hormones/neurotransmitters. Because its activation results in the direct
      activation of many cellular signaling cascades that have been shown to mediate
      CCK's effect in acinar cell function our results suggest that it is one of the
      important pancreatic SFKs mediating these effects.

PMID- 22617840
TI  - Transfer of chirality from ligands to metal centers: recent examples.
AB  - Recent examples of "chiral at metal" complexes and assemblies that are produced
      by chirality transfer of information from enantiopure ligands to metal ions are
      reported. They highlight the new progress that has been made in this area in the
      last two years and the new tendencies that such a topic is following. Besides the
      fundamental aspects related to the stereoselective synthesis of chiral complexes,
      the progress in diverse classes of chiral complexes for applications in materials
      science (chiral switches and molecular machines, biological mimics, CPL probes,
      etc.) is reported.

PMID- 22617838
TI  - Role of novel type I interferon epsilon in viral infection and mucosal immunity.
AB  - Intranasal infection with vaccinia virus co-expressing interferon epsilon (VV-HIV
      IFN-epsilon) was used to evaluate the role of IFN-epsilon in mucosal immunity. VV
      HIV- IFN-epsilon infection induced a rapid VV clearance in lung that correlated
      with (i) an elevated lung VV-specific CD8(+)CD107a(+)IFN-gamma(+) population
      expressing activation markers CD69/CD103, (ii) enhanced lymphocyte recruitment to
      lung alveoli with reduced inflammation, and (iii) an heightened
      functional/cytotoxic CD8(+)CD4(+) T-cell subset (CD3(hi)CCR7(hi)CD62L(lo)) in
      lung lymph nodes. These responses were different to that observed with intranasal
      VV-HA-IFN-alpha(4) or VV-HA-IFN-beta infections. When IFN-epsilon was used in an
      intranasal/intramuscular heterologous HIV prime-boost immunization, elevated HIV
      specific effector, but not memory CD8(+)T cells responses, were observed in
      spleen, genito-rectal nodes, and Peyer's patch. Homing marker alpha4beta7 and
      CCR9 analysis indicated that unlike other type I IFNs, IFN-epsilon could promote
      migration of antigen-specific CD8(+)T cells to the gut. Our results indicate that
      IFN-epsilon has a unique role in the mucosae and most likely can be used to
      control local lung and/or gut infections (i.e., microbicide) such as
      tuberculosis, HIV-1, or sexually transmitted diseases.

PMID- 22617839
TI  - Regulatory role of suppressive motifs from commensal DNA.
AB  - The microbiota contributes to the induction of both effector and regulatory
      responses in the gastrointestinal (GI) tract. However, the mechanisms controlling
      these distinct properties remain poorly understood. We previously showed that
      commensal DNA promotes intestinal immunity. Here, we find that the capacity of
      bacterial DNA to stimulate immune responses is species specific and correlated
      with the frequency of motifs known to exert immunosuppressive function. In
      particular, we show that the DNA of Lactobacillus species, including various
      probiotics, is enriched in suppressive motifs able to inhibit lamina propria
      dendritic cell activation. In addition, immunosuppressive oligonucleotides
      sustain T(reg) cell conversion during inflammation and limit pathogen-induced
      immunopathology and colitis. Altogether, our findings identify DNA-suppressive
      motifs as a molecular ligand expressed by commensals and support the idea that a
      balance between stimulatory and regulatory DNA motifs contributes to the
      induction of controlled immune responses in the GI tract and gut immune
      homeostasis. Further, our findings suggest that the endogenous regulatory
      capacity of DNA motifs enriched in some commensal bacteria could be exploited for
      therapeutic purposes.

PMID- 22617842
TI  - Monte Carlo simulated correction factors for machine specific reference field
      dose calibration and output factor measurement using fixed and iris collimators
      on the CyberKnife system.
AB  - Monte Carlo (MC) simulation of dose to water and dose to detector has been used
      to calculate the correction factors needed for dose calibration and output factor
      measurements on the CyberKnife system. Reference field ionization chambers
      simulated were the PTW 30006, Exradin A12, and NE 2571 Farmer chambers, and small
      volume chambers PTW 31014 and 31010. Correction factors for Farmer chambers were
      found to be 0.7%-0.9% larger than those determined from TRS-398 due mainly to the
      dose gradient across the chamber cavity. For one microchamber where comparison
      was possible, the factor was 0.5% lower than TRS-398 which is consistent with
      previous MC simulations of flattening filter free Linacs. Output factor detectors
      simulated were diode models PTW 60008, 60012, 60017, 60018, Sun Nuclear edge
      detector, air-filled microchambers Exradin A16 and PTW 31014, and liquid-filled
      microchamber PTW 31018 microLion. Factors were generated for both fixed and iris
      collimators. The resulting correction factors differ from unity by up to +11% for
      air-filled microchambers and -6% for diodes at the smallest field size (5 mm),
      and tend towards unity with increasing field size (correction factor magnitude
      <1% for all detectors at field sizes >15 mm). Output factor measurements
      performed using these detectors with fixed and iris collimators on two different
      CyberKnife systems showed initial differences between detectors of >15% at 5 mm
      field size. After correction the measurements on each unit agreed within ~1.5% at
      the smallest field size. This paper provides a complete set of correction factors
      needed to apply a new small field dosimetry formalism to both collimator types on
      the CyberKnife system using a range of commonly used detectors.

PMID- 22617843
TI  - A Fresnel zone plate biosensor for signal amplification with enhanced signal-to
      noise ratio.
AB  - We describe a signal amplified biosensor based on self-assembled optical
      diffraction grating of a Fresnel zone plate structure. Diffracted light rays
      passed through gratings are interfered constructively at the focal point,
      resulting in the enhanced signal amplification without sacrificing signal-to
      noise ratio (SNR).

PMID- 22617841
TI  - Bekesy's contributions to our present understanding of sound conduction to the
      inner ear.
AB  - In our daily lives we hear airborne sounds that travel primarily through the
      external and middle ear to the cochlear sensory epithelium. We also hear sounds
      that travel to the cochlea via a second sound-conduction route, bone conduction.
      This second pathway is excited by vibrations of the head and body that result
      from substrate vibrations, direct application of vibrational stimuli to the head
      or body, or vibrations induced by airborne sound. The sensation of bone-conducted
      sound is affected by the presence of the external and middle ear, but is not
      completely dependent upon their function. Measurements of the differential
      sensitivity of patients to airborne sound and direct vibration of the head are
      part of the routine battery of clinical tests used to separate conductive and
      sensorineural hearing losses. Georg von Bekesy designed a careful set of
      experiments and pioneered many measurement techniques on human cadaver temporal
      bones, in physical models, and in human subjects to elucidate the basic
      mechanisms of air- and bone-conducted sound. Looking back one marvels at the
      sheer number of experiments he performed on sound conduction, mostly by himself
      without the aid of students or research associates. Bekesy's work had a profound
      impact on the field of middle-ear mechanics and bone conduction fifty years ago
      when he received his Nobel Prize. Today many of Bekesy's ideas continue to be
      investigated and extended, some have been supported by new evidence, some have
      been refuted, while others remain to be tested.

PMID- 22617844
TI  - Immunogenicity and safety of measles-mumps-rubella and varicella vaccines
      coadministered with a fourth dose of Haemophilus influenzae type b and Neisseria
      meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine in toddlers: a
      pooled analysis of randomized trials.
AB  - A pooled analysis was conducted of 1257 toddlers who received a fourth dose of
      Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus
      toxoid conjugate vaccine (HibMenCY-TT) or Hib conjugate vaccine (Hib
      polysaccharide conjugated to N. meningitidis outer membrane protein)
      coadministered with measles-mumps-rubella (MMR) and varicella (VAR) vaccines
      (NCT00134719/NCT00289783). Noninferiority of immunological responses to MMR and
      VAR was demonstrated between groups and incidences of MMR- and VAR-specific
      solicited symptoms were similar, indicating that HibMenCY-TT can be
      coadministered with MMR and VAR.

PMID- 22617845
TI  - Host responses to live-attenuated Venezuelan equine encephalitis virus (TC-83):
      comparison of naive, vaccine responder and nonresponder to TC-83 challenge in
      human peripheral blood mononuclear cells.
AB  - Venezuelan equine encephalitis virus (VEEV) is a positive-strand RNA Alphavirus
      endemic in Central and South America, and the causative agent of fatal
      encephalitis in humans. In an effort to better understand the mechanisms of
      infection, including differences between people who produce a neutralizing
      antibody response to the vaccine and those who do not, we performed whole genome
      transcriptional analysis in human PBMCs exposed in vitro to the live-attenuated
      vaccine strain of VEEV, TC-83. We compared the molecular responses in cells from
      three groups of individuals: naive; previously vaccinated individuals who
      developed a neutralizing antibody response to the vaccine (responders); and those
      who did not develop a neutralizing antibody response to the vaccine
      (nonresponders). Overall, the changes in gene expression were more intense for
      the naive group after TC-83 challenge and least potent in the nonresponder group.
      The main canonical pathways revealed the involvement of interferon and interferon
      induced pathways, as well as toll-like receptors TLR- and interleukin (IL)-12
      related pathways. HLA class II genotype and suppression of transcript expression
      for TLR2, TLR4 and TLR8 in the nonresponder group may help explain the lack of
      vaccine response in this study group. Because TL3 and TLR7 transcripts were
      elevated in all study groups, these factors may be indicators of the infection
      and not the immunological state of the individuals. Biomarkers were identified
      that differentiate between the vaccine responder and the vaccine nonresponder
      groups. The identified biomarkers were contrasted against transcripts that were
      unique to the naive population alone upon induction with TC-83. Biomarker
      analysis allowed for the discernment between the naive (innate) responses; the
      responder (recall) responses; and the nonresponder (alternative) changes to gene
      transcription that were caused by infection with TC-83. The study also points to
      the existence of HLA haplotypes that may discriminate between vaccine low- and
      high-responder phenotypes.

PMID- 22617847
TI  - Investigating nonrestorative sleep.

PMID- 22617846
TI  - A murine model of muscle training by neuromuscular electrical stimulation.
AB  - Neuromuscular electrical stimulation (NMES) is a common clinical modality that is
      widely used to restore (1), maintain (2) or enhance (3-5) muscle functional
      capacity. Transcutaneous surface stimulation of skeletal muscle involves a
      current flow between a cathode and an anode, thereby inducing excitement of the
      motor unit and the surrounding muscle fibers. NMES is an attractive modality to
      evaluate skeletal muscle adaptive responses for several reasons. First, it
      provides a reproducible experimental model in which physiological adaptations,
      such as myofiber hypertophy and muscle strengthening (6), angiogenesis (7-9),
      growth factor secretion (9-11), and muscle precursor cell activation (12) are
      well documented. Such physiological responses may be carefully titrated using
      different parameters of stimulation (for Cochrane review, see (13)). In addition,
      NMES recruits motor units non-selectively, and in a spatially fixed and
      temporally synchronous manner (14), offering the advantage of exerting a
      treatment effect on all fibers, regardless of fiber type. Although there are
      specified contraindications to NMES in clinical populations, including peripheral
      venous disorders or malignancy, for example, NMES is safe and feasible, even for
      those who are ill and/or bedridden and for populations in which rigorous exercise
      may be challenging. Here, we demonstrate the protocol for adapting commercially
      available electrodes and performing a NMES protocol using a murine model. This
      animal model has the advantage of utilizing a clinically available device and
      providing instant feedback regarding positioning of the electrode to elicit the
      desired muscle contractile effect. For the purpose of this manuscript, we will
      describe the protocol for muscle stimulation of the anterior compartment muscles
      of a mouse hindlimb.

PMID- 22617848
TI  - WAVE2-Abi2 complex controls growth cone activity and regulates the multipolar
      bipolar transition as well as the initiation of glia-guided migration.
AB  - Glia-guided migration (glia-guided locomotion) during radial migration is a
      characteristic yet unique mode of migration. In this process, the directionality
      of migration is predetermined by glial processes and not by growth cones. Prior
      to the initiation of glia-guided migration, migrating neurons transform from
      multipolar to bipolar, but the molecular mechanisms underlying this multipolar
      bipolar transition and the commencement of glia-guided migration are not fully
      understood. Here, we demonstrate that the multipolar-bipolar transition is not
      solely a cell autonomous event; instead, the interaction of growth cones with
      glial processes plays an essential role. Time-lapse imaging with lattice assays
      reveals the importance of vigorously active growth cones in searching for
      appropriate glial scaffolds, completing the transition, and initiating glia
      guided migration. These growth cone activities are regulated by Abl kinase and
      Cdk5 via WAVE2-Abi2 through the phosphorylation of tyrosine 150 and serine 137 of
      WAVE2. Neurons that do not display such growth cone activities are mispositioned
      in a more superficial location in the neocortex, suggesting the significance of
      growth cones for the final location of the neurons. This process occurs in spite
      of the "inside-out" principle in which later-born neurons are situated more
      superficially.

PMID- 22617849
TI  - Action understanding within and outside the motor system: the role of task
      difficulty.
AB  - When we observe actions, we activate parietal and premotor areas that are also
      recruited when we perform actions ourselves. It has been suggested that this
      action mirroring is causally involved in the process of action understanding.
      Alternatively, it might reflect the outcome of action understanding, with the
      underlying cognitive processes taking place elsewhere. To identify and
      characterize areas involved in action understanding, we presented participants
      with point-light displays depicting human actions and engaged them in tasks that
      required identifying the effector (arm/leg) or the goal of an action. We observed
      a stronger blood oxygen level-dependent signal during the Goal in comparison to
      the Effector Task not only in premotor areas, but also in the middle temporal
      gyrus (MTG) and the anterior ventrolateral prefrontal cortex. In the MTG, the
      Goal Task led to a signal higher than the Effector Task only when actions were
      easy to understand, whereas frontal areas showed this difference also when the
      task was difficult, a finding that is not caused by a ceiling effect. Our results
      suggest an interplay between temporal and frontal areas that is modulated by task
      difficulty and thus provide important constraints for biologically plausible
      models of action understanding.

PMID- 22617850
TI  - Cerebellum and cognition: evidence for the encoding of higher order rules.
AB  - Converging anatomical and functional evidence suggests that the cerebellum
      processes both motor and nonmotor information originating from the primary motor
      cortex and prefrontal cortex, respectively. However, it has not been established
      whether the cerebellum only processes prefrontal information where rules specify
      actions or whether the cerebellum processes any form of prefrontal information no
      matter how abstract. Using functional magnetic resonance imaging, we distinguish
      between two competing hypotheses: (1) activity within prefrontal-projecting
      cerebellar lobules (Crus I and II) will only be evoked by rules that specify
      action (i.e. first-order rules; arbitrary S-R mappings) and (2) activity will be
      evoked in these lobules by both first-order rules and second-order rules that
      govern the application of lower order rules. The results showed that prefrontal
      projecting cerebellar lobules Crus I and II were commonly activated by processing
      both first- and second-order rules. We demonstrate for the first time that
      cerebellar circuits engage both first- and second-order rules and in doing so
      show that the cerebellum can contribute to cognitive control independent of motor
      control.

PMID- 22617851
TI  - Testosterone-related cortical maturation across childhood and adolescence.
AB  - Neuroendocrine theories of brain development hold testosterone as the predominant
      factor mediating sex-specific cortical growth and the ensuing lateralization of
      hemispheric function. However, studies to date have focussed on prenatal
      testosterone rather than pubertal changes in testosterone. Yet, animal studies
      have shown a high density of androgen-sensitive receptors in multiple key
      cortical areas, and puberty is known to coincide with both a significant rise in
      testosterone and the emergence of behavioral sex differences, suggesting
      peripubertal influences of testosterone on brain development. Here, we used
      linear mixed models to examine sex-specific cortical maturation associated with
      changes in testosterone levels in a longitudinal sample of developmentally
      healthy children and adolescents. A significant "sex by age by testosterone"
      interaction on cortical thickness (CTh) involving widespread areas of the
      developing brain was found. Testosterone levels were associated with CTh changes
      in regions of the left hemisphere in males and of the right hemisphere in
      females. In both sexes, the relationship between testosterone and CTh varied
      across the age span. These findings show the association between testosterone and
      CTh to be complex, highly dynamic, and to vary, depending on sex and age; they
      also suggest sex-related hemispheric lateralization effects of testosterone in
      humans.

PMID- 22617852
TI  - COMT x DRD4 epistasis impacts prefrontal cortex function underlying response
      control.
AB  - The prefrontal cortex plays a major role in cognitive control, but it is unclear
      how single genes and gene-gene interactions (genetic epistasis) impact neural and
      behavioral phenotypes. Both dopamine (DA) availability ("inverted U-model") and
      excitatory versus inhibitory DA receptor stimulation ("dual-state theory") have
      been linked to important principles of prefrontal processing. Catechol-O
      methyltransferase (COMT; Val158Met) and DA D4-receptor (DRD4; 48 bp VNTR)
      genotypes were analyzed for effects on behavioral and neural correlates of
      prefrontal response control (NoGo-anteriorization, NGA) using a Go-NoGo task and
      electroencephalography (114 controls and 181 patients with attention
      deficit/hyperactivity disorder).  DRD4 and COMT epistatically interacted on the
      NGA, whereas single genes and diagnosis showed no significant impact. Subjects
      with presumably relatively increased D4-receptor function (DRD4: no 7R-alleles)
      displayed an inverted U-relationship between the NGA and increasing COMT
      dependent DA levels, whereas subjects with decreased D4-sensitivity (7R) showed a
      U-relationship. This interaction was supported by 7R-allele dose effects and
      mirrored by reaction time variability (non-significant after multiple testing
      correction). Combining previous theories of prefrontal DA functioning, neural
      stability at intermediate DA levels may be accompanied by the risk of overly
      decreased neural flexibility if inhibitory DA receptor function is additionally
      decreased. Our findings might help to disentangle the genetic basis of
      dopaminergic mechanisms underlying prefrontal (dys)function.

PMID- 22617853
TI  - Action and outcome activity state patterns in the anterior cingulate cortex.
AB  - Although there are numerous theories regarding anterior cingulate cortex (ACC)
      function, most suggest that it is involved in some form of action or outcome
      processing. The present study characterized the dominant patterns of ACC activity
      on a task in which actions and outcomes could vary independently. Patterns of
      activity were detected using a modified form of principal component analysis
      (PCA), termed constrained PCA in which a regression procedure was applied prior
      to PCA to eliminate the contribution of nontask-related activity. When trials
      were grouped according to outcome, a PC was found in all subjects and sessions
      that had large fluctuations during actions but only differentiated correct versus
      error trials prior to the end of the delay and again at time of the outcome.
      Another PC was always present that separated right from left lever presses, but
      only around the time of the actual lever press. Individual neurons exhibited
      significant selectivities for trials involving different actions and/or outcomes.
      Of the ACC neurons that exhibited significant outcome selectivity, the majority
      fired more on error trials. The present study revealed separate as well as
      integrated action and outcome monitoring in the ACC, especially, although not
      exclusively, under conditions when an error is likely.

PMID- 22617854
TI  - Clonal identity determines astrocyte cortical heterogeneity.
AB  - Astrocytes are the most numerous cell type in the brain, where they are known to
      play multiple important functions. While there is increasing evidence of their
      morphological, molecular, and functional heterogeneity, it is not clear whether
      their positional and morphological identities are specified during brain
      development. We address this problem with a novel strategy to analyze cell
      lineages through the combinatorial expression of fluorescent proteins. Following
      in utero electroporation, stochastic expression of these proteins produces
      inheritable marks that enable the long-term in vivo tracing of glial progenitor
      lineages. Analyses of clonal dispersion in the adult cortex revealed
      unanticipated and highly specific clonal distribution patterns. In addition to
      the existence of clonal arrangements in specific domains, we found that different
      classes of astrocytes emerge from different clones. This reinforces the view that
      lineage origin impinges on cell heterogeneity, unveiling a new level of astrocyte
      diversity likely associated with specific regional functions.

PMID- 22617855
TI  - The 50 most cited articles in pediatric orthopedic surgery.
AB  - Quantity of citation is often used as a surrogate measurement of an article's
      importance or relevance in a given field. To date, there has been no study on
      citation quantity or density in pediatric orthopedics. We present such an
      analysis. We reviewed all articles in the ISI web of science under the subheading
      'orthopedics' to find articles of relevance to pediatric orthopedic surgeons. We
      subsequently analyzed the characteristics of the most cited articles in terms of
      the level of evidence, journal of publication, and subcategory of pediatric
      orthopedics. The majority of the top 50 articles in pediatric orthopedics were
      from the 1970s and 1980s. All the articles were in English. Uncontrolled case
      series comprised the largest single level of evidence (level IV). We describe the
      top 50 articles in pediatric orthopedics by citation and citation density. The
      level of evidence for highly cited papers was low. Although many of these
      articles were written by the great thinkers of our field, a need exists for more
      rigorous methodology.

PMID- 22617856
TI  - Role of molecular architecture on the relative efficacy of aurein 2.5 and modelin
      5.
AB  - In order to gain an insight into the mechanism of antimicrobial peptide action,
      aurein 2.5 and modelin-5 were studied. When tested against Staphylococcus aureus,
      aurein 2.5 showed approximately 5-fold greater efficacy even though the higher
      net positive charge and higher helix stability shown by modelin-5 would have
      predicated modelin-5 to be the more effective antimicrobial. However, in the
      presence of S. aureus membrane mimics, aurein 2.5 showed greater helical content
      (75% helical) relative to modelin-5 (51% helical) indicative of increase in
      membrane association. This was supported by monolayer data showing that aurein
      2.5 (6.6mNm(-1)) generated greater pressure changes than modelin-5 (5.3mNm(-1)).
      Peptide monolayers indicted that modelin-5 formed a helix horizontal to the plane
      of an asymmetric interface which would be supported by the even distribution of
      charge and hydrophobicity along the helical long axis and facilitate lysis by non
      specific membrane binding. In contrast, a groove structure observed on the
      surface of aurein 2.5 was predicted to be the cause of enhanced lipid binding
      (K(d)=75MUM) relative to modelin-5 (K(d)=118MUM) and the balance of
      hydrophobicity along the aurein 2.5 long axis supported deep penetration into the
      membrane in a tilt formation. This oblique orientation generates greater lytic
      efficacy in high anionic lipid (71%) compared to modelin-5 (32%).

PMID- 22617857
TI  - Electrochemical DNA three-way junction based sensor for distinguishing chiral
      metallo-supramolecular complexes.
AB  - Here we report a signal-on three-way junction based-electrochemical DNA sensor
      for distinguishing chiral metallo-supramolecular complexes with an
      enantioselective recognition ratio of about 3.5. This platform is easy to
      fabricate, simple to operate and readily regenerated.

PMID- 22617859
TI  - Treating hypoxia in a feeble breather with Rett syndrome.
AB  - Rett syndrome (RS) is a unique X-linked dominant neurodevelopmental disorder
      affecting 1 in 10,000 females. Mutations in the MECP2 gene located on Xq28 have
      been identified. Many of the characteristic features evolve due to immaturity of
      the brain in RS. Cardiorespiratory function should be investigated early to
      characterise the clinical phenotype of the person with RS because each of the
      three cardiorespiratory phenotypes; apneustic, feeble and forceful breathers have
      unique and different management strategies. We report a case of a feeble breather
      showing a correlation between cortical function and tissue pO(2) and pCO(2). We
      conclude that subtle changes in the levels of blood gases significantly affect
      cortical function in RS.

PMID- 22617860
TI  - A 9-week, randomized, double-blind, placebo-controlled, parallel-group, dose
      finding study to evaluate the efficacy and safety of modafinil as treatment for
      adults with ADHD.
AB  - OBJECTIVE: This study evaluated the efficacy and tolerability of modafinil at a
      range of doses, versus placebo, in alleviating symptoms of ADHD in adults.
      METHOD: Adult patients with ADHD were randomized in 1:1:1:1:1 fashion to double
      blind treatment with modafinil 255, 340, 425, or 510 mg daily or placebo for 9
      weeks. The primary efficacy outcome was the change from baseline at final visit
      in the Adult ADHD Investigator Symptom Rating Scale (AISRS) total score. RESULTS:
      A total of 338 patients were enrolled, of whom 330 received at least 1 dose of
      study medication (modafinil or placebo). No statistically significant difference
      in the AISRS total score was observed at final visit between any modafinil group
      and placebo; however, some observations among patients who completed the trial
      may warrant further investigation. CONCLUSION: Modafinil was reasonably tolerated
      but did not demonstrate a benefit on ADHD symptoms in adults.

PMID- 22617861
TI  - Does stimulant pretreatment modify atomoxetine effects on core symptoms of ADHD
      in children assessed by quantitative measurement technology?
AB  - OBJECTIVE: To compare the reduction of ADHD symptoms under atomoxetine (ATX) in
      patients with and without pretreatment with a stimulant medication using a
      computer-based Continuous Performance Test (cb-CPT) combined with an infrared
      motion tracking (MT) device. METHOD: Double-blind, placebo-controlled study in
      ADHD patients (6-12 years) treated with ATX (target dose = 1.2 mg/kg per day).
      The cb-CPT/MT scores were analyzed using ANCOVA (last observation carried
      forward). RESULTS: Patient data (n = 125) suggested a differential ATX treatment
      effect between pretreated and stimulant-naive patients in terms of three cb
      CPT/MT parameters. CONCLUSION: This secondary analysis provided evidence that ATX
      reduced ADHD symptom severity measured by cb-CPT/MT parameters regardless of
      stimulant pretreatment. A few differential effects were seen based on the cb
      CPT/MT. However, no clear pattern could be identified and, overall, the observed
      differences have no larger clinical relevance. The ATX effect in this study
      seemed to be largely independent of any previous exposure to stimulants.

PMID- 22617862
TI  - Handwriting in children with ADHD.
AB  - OBJECTIVE: Children with ADHD-combined type (ADHD-CT) display fine and gross
      motor problems, often expressed as handwriting difficulties. This study aimed to
      kinematically characterize the handwriting of children with ADHD using a cursive
      letter l's task. METHOD: In all, 28 boys (7-12 years), 14 ADHD-CT and 14
      typically developing (TD), without developmental coordination disorder (DCD) or
      comorbid autism, wrote a series of four cursive letter l's using a graphics
      tablet and stylus. RESULTS: Children with ADHD-CT had more inconsistent writing
      size than did TD controls. In addition, ADHD-CT symptom severity, specifically
      inattention, predicted poorer handwriting outcomes. CONCLUSION: In a sample of
      children with ADHD-CT who do not have DCD or autism, subtle handwriting
      differences were evident. It was concluded that handwriting might be impaired in
      children with ADHD in a manner dependent on symptom severity. This may reflect
      reports of underlying motor impairment in ADHD.

PMID- 22617863
TI  - Risk screening for ADHD in a college population: is there a relationship with
      academic performance?
AB  - OBJECTIVE: The present study examines the relationship between self-reported
      levels of ADHD and academic outcomes, as well as aptitude. METHOD: A total of 523
      college students took the Adult Self-Report Scale-Version 1.1 (ASRS-V1.1), and
      their scores were compared with course performance and ACT (American College
      Test) composite scores. RESULTS: The measure identified 70 students (13.4%) as
      being in the "highly likely" category for an ADHD diagnosis. Course exam and ACT
      scores for the 70 "highly likely" students were statistically identical to the
      remaining 453 students in the sample and the 77 students identified as "highly
      unlikely" as well. Only 4 of the "highly likely" 70 students were registered with
      the university's Office of Student Disability Services as having been diagnosed
      with ADHD. CONCLUSIONS: The ASRS-V1.1 failed to discriminate academic performance
      and aptitude differences between ADHD "highly likely" and "highly unlikely"
      individuals. The use of self-report screeners of ADHD is questioned in contexts
      relating ADHD to academic performance.

PMID- 22617864
TI  - In search of "anything that would help": parent perspectives on emerging
      neurotechnologies.
AB  - OBJECTIVE: This qualitative study explores parents' perceptions about the future
      clinical translation of neurotechnologies--neuroimaging and genetic testing
      separately and together--for instrumentalization in the diagnosis and treatment
      of childhood ADHD. METHOD: We conducted in-person, semi-structured interviews
      with parents of minor children diagnosed with ADHD (N = 26) and analyzed 11.75 hr
      of data using constant comparative analysis. RESULTS: Receptivity to technology
      and anticipation of potential benefits overshadowed discussion of risks or
      concerns. Four key areas of potential impact on parent experience are (a) insight
      and acceptance, (b) treatment and adherence, (c) stigma and blame, and (d) the
      endeavor to access resources. CONCLUSION: The findings highlight high receptivity
      to emerging neurotechnologies for ADHD, key areas for which parents anticipate
      support from these technologies, and ethics challenges to clinical translation in
      light of parents' salient hope and minimal consideration of risk in their pursuit
      of "anything that would help."

PMID- 22617865
TI  - BehaviorLENS [Computer Software] (2012). SuperPsyched LLC.

PMID- 22617866
TI  - EEG neurofeedback for ADHD: double-blind sham-controlled randomized pilot
      feasibility trial.
AB  - OBJECTIVE: Preparing for a definitive randomized clinical trial (RCT) of
      neurofeedback (NF) for ADHD, this pilot trial explored feasibility of a double
      blind, sham-controlled design and adherence/palatability/relative effect of two
      versus three treatments/week. METHOD: Unmedicated 6- to 12-year-olds with
      Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) ADHD were
      randomized to active NF versus sham-NF and to 2X versus 3X/week treatment
      frequency. Frequency switch was allowed after Treatment 24. RESULTS: In two
      school years, 39 participants were recruited and 34 (87%) completed all 40
      treatments. Child/parent guesses about assigned treatment were no better than
      chance. At Treatment 24, 38% chose 2X/week and 62% chose 3X/week. Both active NF
      and sham yielded large pre-post improvement on parent ratings but NF no more than
      sham. CONCLUSION: Blinding appears to work, and sham does not prevent
      recruitment/retention. Treatment frequency of 3X/week seems preferred over
      2X/week and was as effective. A large double-blind RCT is feasible and necessary
      to test specific NF effectiveness.

PMID- 22617867
TI  - Why are quasicrystals quasiperiodic?
AB  - In the past two decades significant progress has been made in the search for
      stable quasicrystals, the determination of their structures and the understanding
      of their physical properties. Now, quasiperiodic ordering states are not only
      known for intermetallic compounds, but also for mesoscopic systems such as ABC
      star terpolymers, liquid crystals or different kinds of colloids. However, in
      spite of all these achievements fundamental questions concerning quasicrystal
      formation, growth and stability are still not fully answered. This tutorial
      review introduces the research in these fields and addresses some of the open
      questions concerning the origin of quasiperiodicity.

PMID- 22617868
TI  - Development of an immunochromatographic assay for rapid detection of AAC(6')-Ib
      producing Pseudomonas aeruginosa.
AB  - To detect aminoglycoside 6'-N-acetyltransferase-Ib [AAC(6')-Ib]-producing,
      Pseudomonas aeruginosa isolates which are a frequent cause of nosocomial
      infections in Japan, an immunochromatographic assay was developed using two kinds
      of monoclonal antibodies (mAbs) recognizing AAC(6')-Ib. The results of the
      assessment were fully consistent with those of aac(6')-Ib PCR analyses.

PMID- 22617869
TI  - Self-assembly of twisted tetrachloroperylenediimide chromophores into two
      dimensional brick-stone aggregates: exciton dynamics and photoconductivity.
AB  - 2D self-assembly has been demonstrated in perylenediimides with twisted
      chromophores, in which the pi-pi stacked units are interconnected via hydrogen
      bonding interactions. Spectroscopic measurements and theoretical calculations
      suggest a weak J-type exciton coupling in the assembly. High photoconductivity of
      the 2D crystal makes it a promising candidate for further opto-electronic
      applications.

PMID- 22617870
TI  - New antidepressant strategy based on acute siRNA silencing of 5-HT1A
      autoreceptors.

PMID- 22617872
TI  - Multifunctional imaging probe based on gadofulleride nanoplatform.
AB  - A FAR over-expressed tumor targeting multifunctional imaging probe has been
      fabricated based on gadofulleride nanoplatform. The combination of highly
      efficient MRI contrast enhancement and sensitive fluorescence imaging along with
      the preferential uptake toward FAR tumor cells suggest that the obtained
      multifunctional imaging probe possesses complementary capabilities for anatomical
      resolution and detection sensitivity.

PMID- 22617876
TI  - Complexities of 5'splice site definition: implications in clinical analyses.
AB  - In higher eukaryotes, the 5' splice site (5'ss) is initially recognized through
      an RNA-RNA interaction by U1 small nuclear ribonucleoprotein (U1 snRNP). This
      event represents one of the key steps in initial spliceosomal assembly and many
      disease-associated mutations in humans often disrupt this process. Beside base
      pair complementarity, 5'ss recognition can also be modified by additional factors
      such as RNA secondary structures or the specific binding of other nuclear
      proteins. In this work, we have focused on investigating a few examples of
      changes detected within the 5'ss in patients, that would not be immediately
      considered "disease causing mutations". We show that the splicing outcome of very
      similar mutations can be very different due to variations in trans-acting
      factor(s) interactions and specific context influences. Using several NF1 donor
      sites and SELEX approaches as experimental models, we have examined the binding
      properties of particular sequence motifs such as GGGU found in donor sites, and
      how the sequence context can change their interaction with hnRNPs such as H/F and
      A1/A2. Our results clearly show that even minor differences in local nucleotide
      context can differentially affect the binding ability of these factors to the
      GGGU core. Finally, using a previously identified mutation in KCNH2 that resulted
      in intron retention we show how very similar 5'ss mutations found in patients can
      have a very different splicing outcome due to the neighbouring sequence context,
      thus highlighting the general need to approach splicing problems with suitable
      experimental approaches.

PMID- 22617875
TI  - Evolution of the let-7 microRNA family.
AB  - The increase of bodyplan complexity in early bilaterian evolution is correlates
      with the advent and diversification of microRNAs. These small RNAs guide animal
      development by regulating temporal transitions in gene expression involved in
      cell fate choices and transitions between pluripotency and differentiation. One
      of the two known microRNAs whose origins date back before the bilaterian ancestor
      is mir-100. In Bilateria, it appears stably associated in polycistronic
      transcripts with let-7 and mir-125, two key regulators of development. In
      vertebrates, these three microRNA families have expanded to form a complex system
      of developmental regulators. In this contribution, we disentangle the
      evolutionary history of the let-7 locus, which was restructured independently in
      nematodes, platyhelminths, and deuterostomes. The foundation of a second let-7
      locus in the common ancestor of vertebrates and urochordates predates the
      vertebrate-specific genome duplications, which then caused a rapid expansion of
      the let-7 family.

PMID- 22617877
TI  - Telomeres and disease: enter TERRA.
AB  - Telomere function is tightly regulated in order to maintain chromosomal
      stability. When telomeres become dysfunctional, the replicative capacity of cells
      diminishes and cellular senescence ensues. This can lead to impaired tissue
      replenishment and eventually degenerative disorders, referred to as telomere
      syndromes. Cancer can also develop as a result of the genomic instability
      associated with telomere dysfunction. TERRA (TElomeric Repeat containing RNA) is
      a long non-coding transcript that stems from sub-telomeric regions and continues
      into the telomeric tract and is therefore a hybrid of both sub-telomeric and
      telomeric sequence. In general, increased TERRA transcription is associated with
      telomere shortening and compromised telomere function. Here we will briefly
      outline the general principles behind telomere dysfunction-associated diseases.
      Furthermore, we will discuss the few known links that exist between telomere
      transcription (TERRA) and disease. Finally, we will speculate on how the
      understanding, and eventual manipulation, of TERRA transcription could
      potentially be used in terms of therapeutic strategies.

PMID- 22617879
TI  - Macro lncRNAs: a new layer of cis-regulatory information in the mammalian genome.
AB  - In the past ten years, long non-protein-coding RNAs (lncRNAs) have been shown to
      comprise a major part of the mammalian transcriptome and are predicted from their
      highly specific expression patterns, to play a role in regulating protein-coding
      gene expression in development and disease. Many lncRNAs particularly those lying
      in imprinted clusters, are predominantly unspliced "macro" transcripts that can
      also show a low level of splicing, and both the unspliced and spliced transcript
      have the potential to be functional. Three known imprinted macro lncRNAs have
      been shown to silence from three to ten genes in cis in imprinted gene clusters.
      We review here the potential for functional macro lncRNAs, defined here as
      "inefficiently-spliced lncRNAs" to play a wider cis-regulatory role in the
      mammalian genome. This potential has been underestimated by the inability of
      current RNA-seq technology to annotate unspliced macro lncRNAs.

PMID- 22617880
TI  - Viroid-specific small RNA in plant disease.
AB  - Viroids are the smallest autonomous infectious nucleic acids known today. They
      are non-coding, unencapsidated, circular RNAs with sizes ranging from 250 to 400
      nucleotides and infect certain plants. These RNAs are transcribed by rolling
      circle mechanisms in the plant host's nuclei (Pospiviroidae) or chloroplasts
      (Avsunviroidae). Since viroids lack any open reading frame, their pathogenicity
      has for a long time been a conundrum. Recent findings, however, show that viroid
      infection is associated with the appearance of viroid-specific small RNA (vsRNA).
      These have sizes similar to endogenous small interfering RNA and microRNA and
      thus might alter the normal gene expression in the host plant. In this review we
      will summarize the current knowledge on vsRNA and discuss the current hypotheses
      how they connect to the induced symptoms, which vary dramatically, depending on
      both the plant cultivar and the viroid strain.

PMID- 22617878
TI  - RNA mediated Toll-like receptor stimulation in health and disease.
AB  - Besides their well known functions in storage and translation of information
      nucleic acids have emerged as a target of pattern recognition receptors that
      drive activation of innate immunity. Due to the paucity of building block
      monomers used in nucleic acids, discrimination of host and microbial nucleic
      acids as a means of self/foreign discrimination is a complicated task. Pattern
      recognition receptors rely on discrimination by sequence, structural features and
      spatial compartmentalization to differentiate microbial derived nucleic acids
      from host ones. Microbial nucleic acid detection is important for the sensing of
      infectious danger and initiating an immune response to microbial attack. Failures
      in the underlying recognitions systems can have severe consequences: thus,
      inefficient recognition of microbial nucleic acids may increase susceptibility to
      infectious diseases. On the other hand, excessive immune responses as a result of
      failed self/foreign discrimination are associated with autoimmune diseases. This
      review gives a general overview over the underlying concepts of nucleic acid
      sensing by Toll-like receptors. Within this general framework, we focus on
      bacterial RNA and synthetic RNA oligomers.

PMID- 22617881
TI  - CpG island hypermethylation-associated silencing of small nucleolar RNAs in human
      cancer.
AB  - Much effort in cancer research has focused on the tiny part of our genome that
      codes for mRNA. However, it has recently been recognized that microRNAs also
      contribute decisively to tumorigenesis. Studies have also shown that epigenetic
      silencing by CpG island hypermethylation of microRNAs with tumor suppressor
      activities is a common feature of human cancer. The importance of other classes
      of non-coding RNAs, such as long intergenic ncRNAs (lincRNAs) and transcribed
      ultraconserved regions (T-UCRs) as altered elements in neoplasia, is also gaining
      recognition. Thus, we wondered whether there were other ncRNAs undergoing CpG
      island hypermethylation-associated inactivation in cancer cells. We focused on
      the small nucleolar RNAs (snoRNAs), a subset of ncRNA with a wide variety of
      cellular functions, such as chemical modification of RNA, pre-RNA processing and
      control of alternative splicing. By data mining snoRNA databases and the
      scientific literature, we selected 49 snoRNAs that had a CpG island within <= 2
      Kb or that were processed from a host gene with a 5'-CpG island. Bisulfite
      genomic sequencing of multiple clones in normal colon mucosa and the colorectal
      cancer cell line HCT-116 showed that 46 snoRNAs were equally methylated in the
      two samples: completely unmethylated (n = 26) or fully methylated (n = 20). Most
      interestingly, the host gene-associated 5'-CpG islands of the snoRNAs SNORD123,
      U70C and ACA59B were hypermethylated in the cancer cells but not in the
      corresponding normal tissue. CpG island hypermethylation was associated with the
      transcriptional silencing of the respective snoRNAs. Results of a DNA methylation
      microarray platform in a comprehensive collection of normal tissues, cancer cell
      lines and primary malignancies demonstrated that the observed hypermethylation of
      snoRNAs was a common feature of various tumor types, particularly in leukemias.
      Overall, our findings indicate the existence of a new subclass of ncRNAs,
      snoRNAs, that are targeted by epigenetic inactivation in human cancer.

PMID- 22617882
TI  - Battle of the midgets: innate microRNA networking.
AB  - Natural killer (NK) cells play an important role in the direct killing of
      cancerous and virus-infected cells. One of the important activating receptors
      which mediates this killing is NKG2D. This receptor recognizes various stress
      induced ligands including the major histocompatibility complex class I-related
      chain A and B (MICA and MICB respectively). The mechanisms controlling the
      expression of the NKG2D ligands are not completely understood, yet various
      studies have demonstrated that the expression of the NKG2D ligands is manipulated
      by viruses and by tumor cells in order to escape the NKG2D detection. Cumulative
      data have emphasized that various microRNAs (miRNAs) of both human and viral
      origin control the expression of NKG2D ligands, particularly MICB. Herein we
      review recent findings regarding the miRNA regulation of the NKG2D ligands. We
      propose that these miRNAs generate a complex network of interactions that control
      the expression of the NKG2D ligands under normal conditions and during disease
      development.

PMID- 22617902
TI  - Development of health biotechnology in developing countries: can private-sector
      players be the prime movers?
AB  - Health biotechnology has rapidly become vital in helping healthcare systems meet
      the needs of the poor in developing countries. This key industry also generates
      revenue and creates employment opportunities in these countries. To successfully
      develop biotechnology industries in developing nations, it is critical to
      understand and improve the system of health innovation, as well as the role of
      each innovative sector and the linkages between the sectors. Countries' science
      and technology capacities can be strengthened only if there are non-linear
      linkages and strong interrelations among players throughout the innovation
      process; these relationships generate and transfer knowledge related to
      commercialization of the innovative health products. The private sector is one of
      the main actors in healthcare innovation, contributing significantly to the
      development of health biotechnology via knowledge, expertise, resources and
      relationships to translate basic research and development into new commercial
      products and innovative processes. The role of the private sector has been
      increasingly recognized and emphasized by governments, agencies and international
      organizations. Many partnerships between the public and private sector have been
      established to leverage the potential of the private sector to produce more
      affordable healthcare products. Several developing countries that have been
      actively involved in health biotechnology are becoming the main players in this
      industry. The aim of this paper is to discuss the role of the private sector in
      health biotechnology development and to study its impact on health and economic
      growth through case studies in South Korea, India and Brazil. The paper also
      discussed the approaches by which the private sector can improve the health and
      economic status of the poor.

PMID- 22617911
TI  - Directed differentiation of induced pluripotent stem cells towards T lymphocytes.
AB  - Adoptive cell transfer (ACT) of antigen-specific CD8(+)  cytotoxic T lymphocytes
      (CTLs) is a promising treatment for a variety of  malignancies (1). CTLs can 
      recognize malignant cells by interacting tumor antigens with the T cell 
      receptors (TCR), and release cytotoxins as well as cytokines to kill malignant
      cells. It is known that  less-differentiated and central-memory-like (termed
      highly reactive) CTLs are the optimal population for ACT-based  immunotherapy,
      because these CTLs have a high proliferative potential, are less  prone to
      apoptosis than more differentiated cells and have a higher ability to  respond to
      homeostatic cytokines (2-7).  However, due to  difficulties in obtaining a high
      number of such CTLs from patients, there is an  urgent need to find a new
      approach to generate highly reactive Ag-specific CTLs  for successful ACT-based
      therapies.    TCR transduction of the self-renewable stem cells for immune
      reconstitution has a therapeutic potential for the treatment of diseases (8-10).
      However, the approach to obtain embryonic stem cells (ESCs) from patients is not
      feasible. Although the use of hematopoietic stem cells (HSCs) for therapeutic
      purposes has been widely applied in clinic (11-13), HSCs have reduced
      differentiation and proliferative capacities, and HSCs are difficult to expand in
      in vitro cell culture (14-16).  Recent iPS cell technology and the development of
      an in vitro system for gene delivery are capable of generating iPS cells from
      patients without any surgical approach. In addition, like ESCs, iPS cells possess
      indefinite proliferative capacity in vitro, and have been shown to differentiate
      into hematopoietic cells. Thus, iPS cells have greater potential to be used in
      ACT-based immunotherapy compared to ESCs or HSCs.    Here, we present methods for
      the generation of T  lymphocytes from iPS cells in vitro,  and in vivo
      programming of  antigen-specific CTLs from iPS cells for promoting cancer immune
      surveillance.  Stimulation in vitro with a Notch  ligand drives T cell
      differentiation from iPS cells, and TCR gene transduction  results in iPS cells
      differentiating into antigen-specific T cells in vivo, which prevents tumor
      growth.  Thus, we demonstrate antigen-specific T cell differentiation from iPS
      cells. Our  studies provide a potentially more  efficient approach for generating
      antigen-specific CTLs for ACT-based therapies  and facilitate the  development of
      therapeutic strategies for diseases.

PMID- 22617883
TI  - RNA-binding protein nucleolin in disease.
AB  - Nucleolin is a multifunctional protein localized primarily in the nucleolus, but
      also found in the nucleoplasm, cytoplasm and cell membrane. It is involved in
      several aspects of DNA metabolism, and participates extensively in RNA regulatory
      mechanisms, including transcription, ribosome assembly, mRNA stability and
      translation, and microRNA processing. Nucleolin's implication in disease is
      linked to its ability to associate with target RNAs via its four RNA-binding
      domains and its arginine/glycin-rich domain. By modulating the post
      transcriptional fate of target mRNAs, which typically bear AU-rich and/or G-rich
      elements, nucleolin has been linked to cellular events that influence disease,
      notably cell proliferation and protection against apoptotic death. Through its
      diverse RNA functions, nucleolin is increasingly implicated in pathological
      processes, particularly cancer and viral infection. Here, we review the RNA
      binding activities of nucleolin, its influence on gene expression patterns, and
      its impact upon diseases. We also discuss the rising interest in targeting
      nucleolin therapeutically.

PMID- 22617913
TI  - Long-term comparison of fixed-bearing and mobile-bearing total knee replacements
      in patients younger than fifty-one years of age with osteoarthritis.
AB  - BACKGROUND: There is limited information comparing the results of fixed-bearing
      total knee replacement and mobile-bearing total knee replacement in patients with
      osteoarthritis who are younger than fifty-one years and who have a fixed-bearing
      implant in one knee and a mobile-bearing implant in the other. The purpose of
      this study was to compare our long-term clinical and radiographic results of
      fixed-bearing total knee replacement and mobile-bearing total knee replacement in
      a group of patients from this population. METHODS: We prospectively compared the
      results of 108 patients with osteoarthritis who were younger than fifty-one years
      (mean age, forty-five years) who had received a fixed-bearing prosthesis in one
      knee and a rotating platform mobile-bearing prosthesis in the other. The mean
      follow-up was 16.8 years (range, fifteen to eighteen years). The patients were
      assessed clinically and radiographically. Knee motion and function were assessed
      as a primary outcome. Patients were assessed with questionnaires, and each knee
      was assessed separately. RESULTS: Although there was significant improvement in
      both groups of knees, there was no significant difference between the groups
      (i.e., fixed-bearing and mobile-bearing knees) with regard to the mean
      postoperative knee motion (126 degrees  and 128 degrees , respectively; p =
      0.79), the mean Knee Society knee clinical score (95 and 94 points, respectively;
      p = 0.79), or the Knee Society knee functional score (84 and 85 points,
      respectively; p = 0.19) at the latest follow-up. In the fixed-bearing group, one
      knee was revised because of infection, two for aseptic loosening of the tibial
      component, and two because of wear of the tibial polyethylene insert. In the
      rotating platform mobile-bearing group, two knees were revised because of
      instability and one because of infection. The Kaplan-Meier survivorship for
      revision at 16.8 years of follow-up was 95% (95% confidence interval, 91 to 100)
      for the fixed-bearing prosthesis and 97% (95% confidence interval, 93 to 100) for
      the rotating platform mobile-bearing prosthesis. CONCLUSIONS: Long-term results
      of both fixed and mobile-bearing total knee arthroplasties were encouraging in
      patients who were younger than fifty-one years of age with osteoarthritis.
      However, we found no superiority of the mobile-bearing total knee prosthesis over
      the fixed-bearing total knee prosthesis.

PMID- 22617914
TI  - Good diagnostic performance of early migration as a predictor of late aseptic
      loosening of acetabular cups: results from ten years of follow-up with Roentgen
      stereophotogrammetric analysis (RSA).
AB  - BACKGROUND: Excessive early migration of femoral stems following total hip
      arthroplasty and tibial components following total knee arthroplasty is
      associated with their long-term survival and allows reliable early evaluation of
      implant performance. However, a similar relationship involving acetabular
      components following hip arthroplasty has not been evaluated. This prospective,
      long-term study with clinical and Roentgen stereophotogrammetric analysis (RSA)
      follow-up establishes the existence of this relationship and its associated
      diagnostic performance. METHODS: Thirty-nine consecutive patients (forty-one
      hips) who underwent total hip arthroplasty with a cemented Exeter stem and a
      cemented Exeter all-polyethylene cup had prospective clinical and RSA follow-up.
      Patients were evaluated postoperatively at six weeks, at three, six, and twelve
      months, and annually thereafter. Conventional anteroposterior and lateral
      radiographs were made at six weeks and at two, five, and ten years
      postoperatively as well as when indicated. The mean duration of follow-up (and
      standard deviation) was 9.4 +/- 3.2 years. No patients were lost to follow-up;
      fifteen patients died during the follow-up period. RESULTS: Eleven acetabular
      components were observed to be loose on conventional radiographs after a mean of
      seventy-six months (range, twelve to 140 months). During the first two
      postoperative years, the failed acetabular components showed markedly greater and
      more rapid cranial translation and sagittal rotation. Both cranial translation
      (hazard ratio = 19.9 [95% confidence interval, 4.94 to 80.0], p < 0.001) and
      sagittal rotation (hazard ratio = 11.1 [95% confidence interval, 2.83 to 43.9], p
      = 0.001) were strong risk factors for late aseptic loosening. Eight of the eleven
      failed components showed a distinctive pattern of excessive cranial translation
      combined with excessive sagittal rotation. The associated diagnostic performance
      of two-year cranial translation and/or sagittal rotation for predicting late
      aseptic loosening of the acetabular component was good (area under the receiver
      operating characteristic curve, 0.88 [95% confidence interval, 0.74 to 1.00; p <
      0.001] and 0.84 [95% confidence interval, 0.68 to 1.00; p = 0.001],
      respectively). CONCLUSIONS: Early migration, as measured by RSA at two years
      postoperatively, has good diagnostic capabilities for the detection of acetabular
      components at risk for future aseptic loosening, and this method appears to be an
      appropriate means of assessing the performance of new implants or implant-related
      changes.

PMID- 22617915
TI  - Intra-articular morphology of the knee joint in children with Blount disease: a
      case-control study using MRI.
AB  - BACKGROUND: The clinical and radiographic abnormalities of the lower limb in
      children with Blount disease are well known. However, there is controversy
      regarding the intra-articular morphologic changes in the involved knee joint. The
      purpose of our study was to evaluate the meniscal and articular surface
      morphology in children with Blount disease with use of magnetic resonance imaging
      and to compare these findings with similar measurements in a control group.
      METHODS: Preoperative magnetic resonance imaging scans of the knee of children
      with Blount disease were compared with those of a control group. Coronal and
      sagittal morphometric parameters including the height and width of the menisci,
      thickness of the unossified proximal tibial epiphysis, tibial condylar and
      meniscal inclination, and presence of signal changes and/or tears of the menisci
      were documented. RESULTS: Twenty-six children (thirty-three) knees with Blount
      disease (mean age, 10.5 years) and twenty children without Blount disease (mean
      age, 9.6 years) were identified. The midcoronal medial meniscal height and width
      were greater in the Blount disease group (p < 0.0001). Abnormal signal changes
      were noted in the medial meniscus in twelve limbs (39%) in the Blount group and
      one limb (5%) in the control group (p = 0.008). The mean thickness of the
      unossified cartilage of the proximal medial tibial epiphysis was also greater in
      the Blount disease group (p = 0.0005). The morphology of the menisci and
      unossified cartilage in the lateral compartment did not differ between the two
      groups. The mean tibial condylar and bimeniscal inclinations in the coronal and
      sagittal planes were also similar in both groups. In a multivariate regression
      analysis, only body mass index correlated with the height of the medial meniscus
      in the coronal plane (p = 0.0035) and of the posterior horn of the medial
      meniscus in the sagittal plane (p = 0.0037) in children with Blount disease.
      CONCLUSIONS: Children with Blount disease have increased thickness of the
      chondroepiphysis of the proximal medial aspect of the tibia, increased height and
      width of the medial meniscus, and greater frequency of abnormal signals in the
      posterior horn of the medial meniscus. These morphologic changes may compensate
      for the diminished height of the ossified portion of the medial proximal aspect
      of the tibia in patients with Blount disease.

PMID- 22617916
TI  - Latissimus dorsi tendon transfer for irreparable rotator cuff tears: a systematic
      review.
AB  - BACKGROUND: Massive and irreparable posterior-superior rotator cuff tears present
      a difficult treatment problem. The purpose of this systematic review was to
      critically examine the outcomes of latissimus dorsi tendon transfers for the
      treatment of irreparable rotator cuff tears. METHODS: A systematic review of the
      literature was performed via a search of electronic databases. Two reviewers
      independently assessed the methodological quality of, and extracted relevant data
      from, each included study. In cases in which the outcomes data were similar
      between studies, data were pooled for the purposes of generating summary outcomes
      through the use of frequency-weighted values. RESULTS: Ten studies that fulfilled
      all inclusion and exclusion criteria were included. The frequency-weighted mean
      age was 58.7 years. Patients were followed for a frequency-weighted mean of 45.5
      months (range, twenty-four to 126 months). Patients had a frequency-weighted mean
      adjusted Constant score of 45.9 preoperatively compared with 73.2 postoperatively
      (p < 0.001). The frequency-weighted mean active forward elevation improved from
      101.9 degrees  preoperatively to 137.4 degrees  postoperatively (p < 0.001), and
      the frequency-weighted mean active external rotation improved from 16.8 degrees 
      to 26.7 degrees  (p < 0.001). Subscapularis muscle insufficiency, advanced teres
      minor muscle atrophy, and the need for revision surgery were correlated with poor
      functional outcomes in some studies. CONCLUSIONS: Compiled data and frequency
      weighted means demonstrated improvement in shoulder function, range of motion,
      strength, and pain relief after latissimus dorsi tendon transfer for irreparable
      rotator cuff tears. Patients and physicians should not expect an outcome of
      "normal" function or complete pain relief.

PMID- 22617917
TI  - Peroneus brevis tendon transfer for reconstruction of chronic tears of the
      Achilles tendon: a long-term follow-up study.
AB  - BACKGROUND: Chronic tears of the Achilles tendon can result in substantial loss
      of function. Those tears with a tendon gap of up to 6.5 cm can be treated
      surgically with use of an autologous peroneus brevis tendon graft. METHODS: At an
      average follow-up period of 15.5 years after the surgery, we examined sixteen of
      twenty-two patients who had undergone peroneus brevis tendon graft reconstruction
      for a chronic Achilles tendon tear. Clinical and functional assessment was
      performed. RESULTS: All sixteen patients were able to walk on tiptoe, and no
      patient used a heel lift or walked with a visible limp. The maximum calf
      circumference of the involved limb remained significantly decreased. The involved
      limb was significantly less strong than the contralateral one. One patient had
      developed a tendinopathy of the opposite Achilles tendon, one had developed a
      tendinopathy of the reconstructed tendon, and one had ruptured the contralateral
      Achilles tendon five years after the original injury. CONCLUSIONS: The long-term
      results of treatment of chronic tears of the Achilles tendon by means of
      autologous peroneus brevis tendon grafting are encouraging. Patients retain good
      functional results despite permanently impaired ankle plantar flexion strength
      and decreased calf circumference.

PMID- 22617918
TI  - Free gracilis tendon graft for reconstruction of chronic tears of the Achilles
      tendon.
AB  - BACKGROUND: Chronic tears of the Achilles tendon with a tendon gap exceeding 6 cm
      are a surgical challenge. The purpose of this study is to report the long-term
      results of reconstruction of such chronic Achilles tendon ruptures with use of a
      free autologous gracilis tendon graft. METHODS: Twenty-one patients underwent
      reconstruction of a chronic rupture of the Achilles tendon. Fifteen patients were
      available for clinical and functional assessment on the basis of anthropometric
      measurements, isometric strength testing, and the Achilles Tendon Total Rupture
      Score after a mean duration of follow-up of 10.9 years (range, eight to twelve
      years). RESULTS: All fifteen patients were able to walk on the tiptoes, and no
      patient used a heel lift or walked with a visible limp. At an average of 10.9
      years of follow-up, the maximum calf circumference of the operatively treated leg
      remained substantially decreased and the operatively treated limb was
      significantly weaker than the contralateral, normal limb. Two patients had
      developed tendinopathy of the contralateral Achilles tendon, one had developed
      tendinopathy of the reconstructed tendon, and one had ruptured the contralateral
      Achilles tendon eight years after the index tear. CONCLUSIONS: The long-term
      results of treatment of chronic tears of the Achilles tendon with free gracilis
      tendon grafting showed that patients retained good functional results despite
      permanently impaired ankle plantar flexion strength and decreased calf
      circumference.

PMID- 22617920
TI  - Effects of glycemic control on prevalence of diabetic frozen shoulder.
AB  - BACKGROUND: There is controversy regarding the influence of glycemic control in
      diabetic patients with frozen shoulder. To determine the relationship between
      glycemic control and the prevalence of frozen shoulder in diabetic patients, we
      hypothesized that increased glycosylated hemoglobin A1c (HbA1c) levels would
      correlate with an increased prevalence of frozen shoulder. METHODS: A
      retrospective analysis with statistical review of 201,513 diabetic patients
      enrolled in a regional health maintenance organization in 2007 was performed.
      Analysis included determining the relationship between the prevalence of frozen
      shoulder and the following factors: HbA1c level, type of diabetes treatment,
      duration of diabetes treatment, and presence of end-stage diabetic
      manifestations. RESULTS: There were 1150 diabetic patients with a diagnosis of
      frozen shoulder. There was no significant relationship between HbA1c level and
      the prevalence of frozen shoulder. Insulin-dependent patients who used or did not
      use oral hypoglycemics were 1.93 times more likely than non-insulin-dependent
      diabetic patients to have frozen shoulder, and that rate increased to 1.96 times
      more likely when the results were adjusted for HbA1c level. Patients who were
      taking oral hypoglycemic drugs were 1.5 times more likely to develop frozen
      shoulder than those who did not use insulin or take oral hypoglycemic drugs.
      Duration of diabetes was also associated with the development of frozen shoulder,
      after controlling for insulin use (odds ratio: 1.85 for duration of more than ten
      years of use compared with less than five years of use). The prevalence of end
      stage diabetic manifestations was increased in patients with frozen shoulder as
      compared with those without frozen shoulder (p < 0.0001). CONCLUSION: There was
      no association found between HbA1c level and the prevalence of frozen shoulder in
      this diabetic population.

PMID- 22617919
TI  - The relationship of sporting activity and implant survivorship after hip
      resurfacing.
AB  - BACKGROUND: The effect of sports on the durability of the prosthesis after hip
      resurfacing has not been studied, to our knowledge. The purpose of this study was
      to correlate sporting activity levels calculated as Impact and Cycle Scores with
      the survivorship of the hip resurfacing implants. METHODS: Four hundred and forty
      five patients were surveyed from one to five years after surgery. The mean age of
      the patients was 48.7 years, and 74% were men. The Impact and Cycle Score
      included two scores: an Impact Score and a Hip Cycle Score. All patients were
      also evaluated with the University of California at Los Angeles activity score.
      Twenty-three patients (twenty-seven hips) underwent revision surgery after they
      had completed the survey. RESULTS: The mean duration of follow-up at the time of
      survey data collection was 1.9 years (range, 1.0 to 4.9 years), and the mean
      follow-up period was 10.2 years (range, 6.1 to 13.7 years). The mean Impact Score
      was 28.1 (range, 0 to 128), and the mean Hip Cycle Score was 33 (range, 0 to
      144). Positive correlations were found between the University of California Los
      Angeles activity score and the Impact Score (r = 0.535) or Hip Cycle Score (r =
      0.497). After adjustment for femoral component size, body mass index, and femoral
      defect size, a 10-point increment in Impact Score corresponded to a 37% increase
      (hazard ratio, 1.37; 95% confidence interval, 1.18 to 1.59) in the risk of
      revision arthroplasty, while a 10-point increment in the Hip Cycle Score
      increased the risk of revision by 22% (hazard ratio, 1.22; 95% confidence
      interval, 1.06 to 1.41).Patients with an Impact Score of < 50 had a risk of
      revision 3.8 times lower (hazard ratio, 3.8; 95% confidence interval, 1.6 to 8.9)
      than that of the patients with an Impact Score of >= 50, with a survivorship rate
      at eight years of 96.4% (95% confidence interval, 93.6% to 98.0%) compared with
      88.8% (95% confidence interval, 74.7% to 95.3%). We found no association between
      the University of California at Los Angeles activity score and the survivorship
      of the implants. CONCLUSIONS: High levels of sporting activities can be
      detrimental to the long-term success of hip resurfacing devices, independently
      from other risk factors. Patients seeking hip resurfacing are usually young and
      should limit their involvement in sports to levels that the implant construct
      will be able to tolerate.

PMID- 22617921
TI  - A comparison of limb-socket kinematics of bone-bridging and non-bone-bridging
      wartime transtibial amputations.
AB  - BACKGROUND: While there are proponents of both bone-bridging and non-bone
      bridging transtibial amputation techniques, there is a lack of evidence
      describing functional differences between these two techniques. The goal of the
      present investigation was to objectively compare the techniques of bone-bridging
      and non-bone-bridging with respect to limb socket displacement during physiologic
      loading. METHODS: Fifteen male subjects with an average age of twenty-seven years
      (range, twenty-two to thirty-two years) who had undergone a unilateral
      transtibial amputation secondary to a traumatic wartime injury were prospectively
      evaluated. Seven patients had undergone a bone-bridging amputation, and eight had
      undergone a non-bone-bridging amputation. Digital fluoroscopic video was used to
      measure the vertical displacement of the limb within a total-surface-bearing
      socket with weight-bearing from 0% to 100% of body weight. RESULTS: There was no
      difference in limb-socket displacement between amputation techniques with initial
      loading (12.78 mm for the bone-bridging group, compared with 12.43 mm for the non
      bone-bridging group; p = 0.88) or with total loading (p = 0.98). Similarly, there
      was no difference between suspension mechanisms in limb-socket displacement with
      initial loading (12.15 mm for patients with pin lock suspension, compared with
      12.98 mm for those with suction sleeve suspension; p = 0.72) or with total
      loading (18.24 mm for patients with pin lock suspension, compared with 21.42 mm
      for those with suction sleeve suspension, p = 0.21). CONCLUSIONS: The current
      study demonstrated no difference between surgical techniques with respect to bone
      socket displacement. These data provide no evidence to support statements that
      bone-bridging contributes to a more efficient platform in the total-surface
      bearing socket.

PMID- 22617922
TI  - Vascular anatomy of the tibiofibular syndesmosis.
AB  - BACKGROUND: Injuries to the tibiofibular syndesmosis commonly cause prolonged
      ankle pain and disability. Syndesmotic injuries are associated with slower
      healing rates compared with rates for other ankle ligament injuries and typically
      result in longer time away from sports. To our knowledge, the vascular supply to
      the syndesmosis and its clinical implication have not previously been studied.
      The purpose of this study was to describe the vascular supply to the tibiofibular
      syndesmosis with use of a method of chemical debridement of cadaveric specimens.
      METHODS: Twenty-five matched pairs of adult cadaver legs, fifty legs total, were
      amputated below the knee. India ink, followed by Ward Blue Latex, was injected
      into the anterior tibial, peroneal, and posterior tibial arteries under constant
      manual pressure to elucidate the vascular supply of the ankle syndesmotic
      ligaments. Chemical debridement was performed with 6.0% sodium hypochlorite to
      remove soft tissue, leaving bones, ligaments, and casts of the vascular anatomy
      intact. The vascular supply to the syndesmosis was evaluated and recorded.
      RESULTS: The anterior vascularity of the syndesmosis was clearly visualized in
      forty-three of fifty specimens. The peroneal artery supplied an anterior branch
      (the perforating branch) that perforated the interosseous membrane, an average of
      3 cm proximal to the ankle joint. This branch provided the primary vascular
      supply to the anterior ligaments in twenty-seven specimens (63%). The anterior
      tibial artery provided additional contribution to the anterior ligaments in the
      remaining sixteen specimens (37%). CONCLUSIONS: The location of the perforating
      branch of the peroneal artery places it at risk when injury to the syndesmosis
      extends to the interosseous membrane 3 cm proximal to the ankle joint. In the
      majority of specimens, injury to this vessel would result in loss of the primary
      blood supply to the anterior ligaments.

PMID- 22617923
TI  - Hip-strengthening exercises before functional exercises reduced pain in women
      with patellofemoral pain syndrome.

PMID- 22617924
TI  - Percutaneous reduction, screw fixation, and calcium sulfate cement grafting was
      effective for displaced intra-articular calcaneal fractures.

PMID- 22617925
TI  - Hemiarthroplasty improved health-related quality of life more than nonoperative
      treatment in older patients with four-part proximal humeral fractures.

PMID- 22617926
TI  - Modern techniques in the treatment of patients with metastatic spine disease.

PMID- 22617927
TI  - What's new in foot and ankle surgery.

PMID- 22617928
TI  - Efficacy of alendronate in the treatment of low bone density in the pediatric and
      young adult population.
AB  - BACKGROUND: Pediatric osteoporosis is uncommon but can result in painful and
      debilitating insufficiency fractures. Treatment options for osteoporosis in
      children are few. Bisphosphonate therapy for children has not been approved by
      the Food and Drug Administration (FDA) in the United States, but its use in that
      population has been increasing. Randomized controlled studies have not been done
      because of the small subject pool and the difficulty in randomizing a child with
      an insufficiency fracture to a placebo arm of a study. This retrospective case
      control study of a population of children with primarily neuromuscular disease
      was done to review changes in bone mineral density as reflected by dual x-ray
      absorptiometry (DXA) scanning. METHODS: Medical records and DXA scans were
      screened to identify children with low bone density who had been treated with
      alendronate as well as similar control subjects with low bone density for their
      age who had not received alendronate. Medication acquisition was confirmed by
      refill records, and cumulative exposure was calculated. Interval DXA scans were
      reviewed to correlate bone mineral density change in grams per square centimeter
      as well as the percent change and percent change over time for both alendronate
      treated and control subjects. RESULTS: Twenty-eight alendronate-treated subjects
      and thirty control subjects met the inclusion criteria. No significant
      improvement in bone mineral density was seen in the alendronate-treated subjects
      as compared with the control subjects. Some patients in both groups exhibited
      marked improvement, with improvement of >31% seen only in the alendronate-treated
      subjects. CONCLUSIONS: Alendronate does not reliably improve bone density in
      children and young adults with primarily neuromuscular disease and without
      osteogenesis imperfecta. Individual patients treated with bisphosphonates must be
      carefully followed to ensure medication compliance and appropriate response.

PMID- 22617929
TI  - Acute compartment syndrome of the forearm.
AB  - BACKGROUND: The aims of this study were to document our experience with acute
      forearm compartment syndrome and to determine the risk factors for the need for
      split-thickness skin-grafting and the development of complications after
      fasciotomy. METHODS: We identified from our trauma database all patients who
      underwent fasciotomy for an acute forearm compartment syndrome over a twenty-two
      year period. Diagnosis was made with use of clinical signs in all patients, with
      compartment pressure monitoring used as a diagnostic adjunct in some patients.
      Outcome measures were the use of split-thickness skin grafts and the
      identification of complications following forearm fasciotomy. RESULTS: There were
      ninety patients in the study cohort, with a mean age of thirty-three years
      (range, thirteen to eighty-one years) and a significant male predominance (eighty
      two patients; p < 0.001). A fracture of the radius or ulna, or both, was seen in
      sixty-two patients (69%), with soft-tissue injuries as the causative factor in
      twenty-eight (31%). The median time to fasciotomy was twelve hours (range, two to
      seventy-two hours). Risk factors for requiring split-thickness skin-grafting were
      younger age and a crush injury (p < 0.05 for both). Risk factors for the
      development of complications were a delay in fasciotomy of more than six hours (p
      = 0.018) and preoperative motor symptoms, which approached significance (p =
      0.068). CONCLUSIONS: Forearm compartment syndrome requiring fasciotomy
      predominantly affects males and can occur following either a fracture or soft
      tissue injury. Age is an important predictor of undergoing split-thickness skin
      grafting for wound closure. Complications occur in a third of patients and are
      associated with an increasing time from injury to fasciotomy.

PMID- 22617930
TI  - Effect of tibial plateau fracture on lubrication function and composition of
      synovial fluid.
AB  - BACKGROUND: Intra-articular fractures may hasten posttraumatic arthritis in
      patients who are typically too active and too young for joint replacement.
      Current orthopaedic treatment principles, including recreating anatomic alignment
      and establishing articular congruity, have not eliminated posttraumatic
      arthritis. Additional biomechanical and biological factors may contribute to the
      development of arthritis. The objective of the present study was to evaluate
      human synovial fluid for friction-lowering function and the concentrations of
      putative lubricant molecules following tibial plateau fractures. METHODS:
      Synovial fluid specimens were obtained from the knees of eight patients (twenty
      five to fifty-seven years old) with a tibial plateau fracture, with five
      specimens from the injured knee as plateau fracture synovial fluid and six
      specimens from the contralateral knee as control synovial fluid. Each specimen
      was centrifuged to obtain a fluid sample, separated from a cell pellet, for
      further analysis. For each fluid sample, the start-up (static) and steady-state
      (kinetic) friction coefficients in the boundary mode of lubrication were
      determined from a cartilage-on-cartilage biomechanical test of friction. Also,
      concentrations of the putative lubricants, hyaluronan and proteoglycan-4, as well
      as total protein, were determined for fluid samples. RESULTS: The group of
      experimental samples were obtained at a mean (and standard deviation) of 11 +/- 9
      days after injury from patients with a mean age of 45 +/- 13 years. Start-up and
      kinetic friction coefficients demonstrated similar trends and dependencies. The
      kinetic friction coefficients for human plateau fracture synovial fluid were
      approximately 100% higher than those for control human synovial fluid. Hyaluronan
      concentrations were ninefold lower for plateau fracture synovial fluid compared
      with the control synovial fluid, whereas proteoglycan-4 concentrations were more
      than twofold higher in plateau fracture synovial fluid compared with the control
      synovial fluid. Univariate and multivariate regression analysis indicated that
      kinetic friction coefficient increased as hyaluronan concentration decreased.
      CONCLUSIONS: Knees afflicted with a tibial plateau fracture have synovial fluid
      with decreased lubrication properties in association with a decreased
      concentration of hyaluronan.

PMID- 22617931
TI  - Validation of the Western Ontario Meniscal Evaluation Tool (WOMET) for patients
      with a degenerative meniscal tear: a meniscal pathology-specific quality-of-life
      index.
AB  - BACKGROUND: Arthroscopic partial meniscectomy is the most common orthopaedic
      procedure and is often carried out to treat a degenerative meniscal lesion. The
      purpose of the present study was to determine the psychometric properties of the
      Western Ontario Meniscal Evaluation Tool (WOMET) for patients with an
      arthroscopically verified degenerative meniscal tear. METHODS: Four hundred and
      eighty-five patients with an arthroscopically verified degenerative meniscal tear
      were included. Two groups of patients were formed: one consisted of 385 patients
      for the purpose of psychometric testing of the WOMET and the other consisted of
      100 patients for the assessment of criterion validity. The reliability of the
      WOMET questionnaire was assessed by determining both internal consistency and
      test-retest repeatability; for the latter, a subgroup of forty patients completed
      the form two weeks preoperatively and again on the day of the operation. Validity
      assessment included determination of content validity (floor and ceiling
      effects), criterion validity (completion of the WOMET, the Lysholm knee score,
      and a generic quality-of-life questionnaire by a group of 100 patients), and
      construct validity (hypothesis testing). Finally, the responsiveness of the WOMET
      was determined with two successive assessments (on the day of surgery and six
      months postoperatively). RESULTS: The WOMET showed acceptable internal
      consistency, test-retest reliability, floor and ceiling effects, criterion
      validity (agreement with both Lysholm and 15-D scores), and construct validity
      (all hypotheses were significant). The WOMET was also found to be responsive to
      change. CONCLUSION: The WOMET score demonstrated acceptable psychometric
      performance as a patient-administered outcome measure for patients with an
      arthroscopically verified degenerative meniscal tear.

PMID- 22617932
TI  - Correcting fixed varus deformity with flexion contracture during total knee
      arthroplasty: the "inside-out" technique: AAOS exhibit selection.
AB  - BACKGROUND: Traditional methods for correcting a severe varus and flexion
      deformity of the knee during total knee arthroplasty can often lead to excessive
      release of the medial collateral ligament, hematoma formation, and reliance on
      constrained implants. The "inside-out" technique for correction of varus
      deformities involves performing a posteromedial capsulotomy at the level of the
      tibial cut and incising the superficial medial collateral ligament in a pie-crust
      manner in extension followed by serial manipulations with valgus stress. Our
      hypothesis was that this technique effectively corrects severe knee varus and
      flexion deformity with a reduced risk of complications. METHODS: Thirty-one
      consecutive patients (thirty-four knees) with a severe fixed varus and flexion
      deformity (varus alignment of >= 15 degrees  and flexion contracture of >= 5
      degrees ) underwent total knee arthroplasty with use of the inside-out technique
      between October 2006 and December 2009. Physical examination, radiographs, and
      multiple outcome instruments were used to evaluate the results. RESULTS: The mean
      duration of follow-up was 3.1 +/- 1.1 years (range, 1.7 to 4.9 years). There were
      no cases of hematoma formation, excessive release of the medial collateral
      ligament, or acute or delayed instability. A semi-constrained TC3 implant was
      used in two cases. The mean preoperative coronal alignment was 21.1 degrees  +/-
      4 degrees  of varus, which was corrected to 4.5 degrees  +/- 1.6 degrees  of
      valgus after surgery. The mean preoperative flexion contracture was 10 degrees 
      +/- 3.5 degrees . Postoperatively, two patients (three knees) had a residual
      flexion contracture, which was <=5 degrees  in all cases. The mean range of knee
      motion improved from 103.3 degrees  +/- 14.1 degrees  preoperatively to 119.1
      degrees  +/- 8 degrees  at the time of final follow-up. The mean Knee Society
      Score pain subscore improved from 39.5 +/- 12.6 to 93.2 +/- 10.5, and the
      function subscore improved from 47.1 +/- 17.8 to 78.5 +/- 21.9. There was no
      evidence of implant loosening or osteolysis on radiographs. CONCLUSIONS: The
      technique described was safe, reproducible, and effective in treating combined
      varus and flexion deformity of the knee during total knee arthroplasty. It
      reduced the risks of over-release of the medial collateral ligament, hematoma
      formation, and the need for constrained implants.

PMID- 22617933
TI  - Eponyms of the Kager triangle.

PMID- 22617934
TI  - Simulated hip arthroscopy skills: learning curves with the lateral and supine
      patient positions: a randomized trial.
AB  - BACKGROUND: Hip arthroscopy can be performed with the patient in the lateral or
      supine position, but it remains technically demanding. We aimed to objectively
      quantify and compare learning curves between two groups of orthopaedic trainees
      randomized to learn simulated hip arthroscopy with the patient in either a
      lateral or a supine position. We also compared learning curves between senior and
      junior trainees. METHODS: A hip arthroscopy simulator with anterolateral and
      anterior portals, a 70 degrees  arthroscope, and fixed distraction was used.
      Rotation of the simulator by 90 degrees  enabled arthroscopy with the patient in
      a supine or lateral position. Twenty orthopaedic trainees with minimal hip
      arthroscopy experience were randomized into lateral and supine position groups,
      and were asked to perform a diagnostic hip arthroscopy of the central compartment
      on twelve occasions. Each episode involved a change in the portal and repetition
      of the diagnostic round. A validated motion analysis system objectively measured
      surgical performance by recording time taken, total path-length of the hands, and
      number of hand movements. RESULTS: Both groups demonstrated learning with
      objective improvement in all parameters (p < 0.001). Initially, the lateral group
      was significantly slower and more variable in their performance during the second
      diagnostic round, after portal exchange (p = 0.006). However, they achieved
      parity with the supine group in all parameters by nine episodes. During the first
      three episodes, the junior trainees performed significantly worse for the first
      diagnostic round (p = 0.005) but not for the second diagnostic round (p = 0.200),
      and they rapidly achieved parity with the senior trainees, performing at a
      similar level by the end of the study period. CONCLUSIONS: Trainees with minimal
      experience with hip arthroscopy progressively learn and objectively improve their
      performance when using a hip simulator. Orientation after portal exchange is
      difficult for all trainees but particularly for those learning with a simulated
      patient lateral position. Trainees are likely to benefit from simulator training
      to learn orientation and basic competence prior to performing hip arthroscopy on
      patients.

PMID- 22617935
TI  - The definitive answer: fixed-bearing versus mobile-bearing TKA: commentary on an
      article by Young-Hoo Kim, MD, et al.: "Long-term comparison of fixed-bearing and
      mobile-bearing total knee replacements in patients younger than fifty-one years
      of age with osteoarthritis".

PMID- 22617936
TI  - Early cup instability with RSA predicts long-term aseptic loosening: commentary
      on an article by Marc J. Nieuwenhuijse, BSc, MD, et al.: "Good diagnostic
      performance of early migration as a predictor of late aseptic loosening of
      acetabular cups. Results from ten years of follow-up with Roentgen
      stereophotogrammetric analysis (RSA)".

PMID- 22617937
TI  - Radiolucent tissue and the straight child: commentary on an article by Sanjeev
      Sabharwal, MD, et al.: "Intra-articular morphology of the knee joint in children
      with Blount disease: a case-control study using MRI".

PMID- 22617938
TI  - Selective TDDFT with automatic removal of ghost transitions: application to a
      perylene-dye-sensitized solar cell model.
AB  - We present an application of a selective time-dependent density-functional theory
      (TDDFT) scheme to a model for a dye-sensitized solar cell (DSSC) with a perylene
      sensitizer dye on a TiO2 nanoparticle model. In an earlier study on this system
      [De Angelis, Chem. Phys. Lett., 2010, 493, 323], it was reported that a large
      number of conduction-band excitations severely complicate the identification of
      the bright pi->pi* excitations of the perylene dye. Here, we show that this
      problem can be overcome by applying a selective TDDFT solver based on a guess for
      the relevant orbital transition in combination with a suitable root-homing
      scheme. In order to enhance the efficiency of this algorithm we implement an
      automatic removal scheme for artificially low-lying long-range charge-transfer
      transitions from the TDDFT eigenvalue problem. A large number of such transitions
      appear in explicitly solvated systems in the form of inter-solvent or solvent
      solute transitions. We study the characteristics of this removal scheme for a
      small water cluster and then apply it in a TDDFT calculation to a perylene-TiO2
      nanoparticle model system and to perylene explicitly solvated in methanol. It is
      demonstrated that this scheme leads to a large reduction in the computational
      cost with essentially no loss in accuracy. Large differences in the effect of
      adsorption on the excited states of perylene dyes with two different anchor
      groups found in earlier work are confirmed. 

PMID- 22617939
TI  - Gold(i)-catalyzed cyclization of 2-(1-alkynyl)-alk-2-en-1-one oximes: a facile
      access to highly substituted N-alkoxypyrroles.
AB  - A gold(i)-catalyzed cyclization of 2-(1-alkynyl)-alk-2-en-1-one oximes with
      numerous nucleophiles has been developed. This strategy provides a relatively
      safe, mild, simple access to a mass of highly substituted N-alkoxypyrroles.

PMID- 22617940
TI  - Gold-catalyzed isomerization of unactivated allenes into 1,3-dienes under ambient
      conditions.
AB  - We have developed a gold-catalyzed isomerization of unactivated allenes into 1,3
      dienes with nitrosobenzene as an additive. This reaction proceeded almost
      exclusively at room temperature for highly substituted allenes. The utility of
      this reaction is manifested by the development of one-pot [4+2]-cycloaddition of
      allenes and reactive alkenes.

PMID- 22617941
TI  - Evaluation of coarse and fine particulate sources using a portable aerosol
      monitor in a desert community.
AB  - The purpose of this study was to use a portable aerosol monitor as a preliminary
      screening tool to identify local sources of coarse (PM(10-2.5)) and fine
      (PM(2.5)) particulate matter within the Coachella Valley, a low-elevation desert
      community. The portable aerosol monitor proved to be useful in identifying
      particle sources unique to the region, namely, sand dunes with sparse ground
      cover (vegetation), a river wash, and diesel truck and freight train traffic. The
      general limitations relate to discrepancies in the fraction of PM(10-2.5) when
      compared to regional air quality data and a lack of accurate mass-based data.

PMID- 22617942
TI  - Toxicity of chloride under winter low-flow conditions in an urban watershed in
      central Missouri, USA.
AB  - Deicers such as sodium chloride and calcium chloride are used to treat snow and
      ice on road surfaces and have been identified as potential stressors on aquatic
      life. Hinkson Creek is an urban stream on the Missouri 303(d) list of impaired
      waters and is classified as impaired due to urban non-point source pollution. A 7
      day toxicity test using Ceriodaphnia dubia was conducted to assess the toxicity
      of stream water during snowmelt at seven sites within the Hinkson Creek
      watershed. Chloride concentrations at two sites (Site 6, 1252 mg Cl/L; Site 4,
      301 mg Cl/L) exceeded the U.S. Environmental Protection Agency chronic criterion
      (230 mg Cl/L). Survival (30 %) and total reproduction (6.9 young/adult) of C.
      dubia at Site 6 was significantly lower than survival (100 %) and total
      reproduction (30.4 young/adult) at Site 1 (reference site). Results indicate that
      chloride concentrations are elevated above water-quality criteria and that
      chloride may be a significant chemical stressor for macroinvertebrate communities
      during winter low-flow conditions in the Hinkson Creek watershed.

PMID- 22617943
TI  - Isolation and characterization of heavy metal resistant bacteria from Barak River
      contaminated with pulp paper mill effluent, South Assam.
AB  - A group of 15 heavy metal resistant bacteria were isolated from Barak River
      contaminated with paper and pulp effluents. These isolates displayed different
      degrees of chromium tolerance. Four isolates showed 34 %-49 % of growth at a
      concentration of 4.0 mM of Cr(6+) and subjected to chromium reduction assay under
      aerobic condition. The isolate E (4) showed highest reduction (34.38 %) followed
      by E (3) and K(6)PA6, both showed 28.75 % reduction and then D (2) (27.5 %) after
      72 h of incubation. These 4 isolates also showed different degrees of resistance
      to other heavy metals like Ni, Cu, Co and Cd. Antibiotic sensitivity profile of
      these selected bacterial strains was determined against 10 different antibiotics.
      Isolate E (4) appeared to be most susceptible being inhibited by eight
      antibiotics and resistant to penicillin G and ampicillin. The isolate E (3) was
      resistant to as many as five antibiotics and showed susceptible responses to the
      rest of the antibiotics. Both the isolates K(6)PA6 and D (2) were resistant to
      four antibiotics and showed intermediate to susceptible responses to the rest of
      the antibiotics.

PMID- 22617944
TI  - Influence of organic amendments on the degradation of endosulfan.
AB  - A laboratory experiment was conducted to study the effect of soil amendments with
      four different sources of organic matter on the dissipation rate of endosulfan.
      Farm yard manure (FYM), vermi compost, leaf compost and charcoal, dried, ground
      (<4 mm) and thoroughly mixed with a calcareous soil at a rate of 2.5 % and placed
      in plastic pots. Endosulfan was added at 10 MUg level. In 30-day incubation
      period the degradation was fastest in vermin compost, 88.48 %, followed by FYM,
      seababul leaves and charcoal, recording 87.21 %, 79.41 % and 68.39 %,
      respectively, as compared to un amended treatment where slow degradation of 65.53
      % was observed. The half life was 18.8 days in un-amended soil as compared to
      1.01-1.29 days in vermi compost, farm yard manure, charcoal and leaf compost. The
      amendment with vermin compost, followed by FYM was found to be most effective and
      enhances the degradation as compared to the other amendments.

PMID- 22617945
TI  - Polychlorinated biphenyls in selected sites in Pasig River and Laguna Lake in the
      Philippines before and after a big flood event investigated under the UNU East
      Asia Regional POPs monitoring project.
AB  - This paper reports the results of the 2009 United Nations University (UNU) East
      Asia Regional Monitoring of the Coastal Hydrosphere Project implemented in the
      Philippines. The monitoring activity focused on the concentrations of 16 specific
      congeners of Polychlorinated Biphenyls in selected sites in Pasig River and
      Laguna Lake for two sampling periods in August and in November, 2009. The results
      show that the total concentrations of PCBs detected in the sampling sites in
      August increased during the November sampling from 0.9-12.2 to 6.1-32 ng/L in
      Pasig River and from 0.1-0.9 to 2.9-10.8 ng/L in Laguna Lake. The increase in PCB
      concentrations on second sampling is attributed to the increase in contaminated
      sediments in the river sites and to the overflow of contaminated water in the
      lake sites; both of which could have been caused by the flooding event that
      occurred in September 2009.

PMID- 22617946
TI  - Simultaneous laccase production and color removal by culturing fungus Pycnoporus
      sp. SYBC-L3 in a textile wastewater effluent supplemented with a lignocellulosic
      waste Phragmites australis.
AB  - We conducted experiments to culture Pycnoporus sp. SYBC-L3 in a medium comprising
      an industrial waste (dye-containing textile effluent) and a lignocellulosic waste
      (Phragmites australis) that achieved laccase production while having the color
      removed from the wastewater. Our experimental results showed that the fungus grew
      well in liquid submerged cultivation with the diluted textile effluent as the
      sole culture medium, but relatively low extracellular laccase activity (1.8 U/mL)
      was produced. Addition of the lignocellulosic biomass enhanced laccase production
      and color removal. The highest laccase activity was found to be 6.5 U/mL in the
      presence of Phragmites australis stem. Under this condition, 70 % color removal
      occurred in the culture medium. This study provided an alternative novel scheme
      to remove color in textile wastewater while having an economic value added by
      producing laccase.

PMID- 22617947
TI  - Mercury and selenium in a top-predator fish, Trichiurus lepturus (Linnaeus,
      1758), from the tropical Brazilian Coast, Rio de Janeiro.
AB  - Muscular mercury and selenium were assessed in a voracious fish from three
      Brazilian coastal areas with different environmental conditions. Mercury was
      higher in specimens from Ilha Grande Bay (0.35 +/- 0.17 MUg g(-1)) than in
      cutlassfish from Guanabara Bay (0.30 +/- 0.15 MUg g(-1)) and Buzios coast (0.13
      +/- 0.08 MUg g(-1)), respectively. No difference was found regarding selenium
      among these areas. Mercury was positively correlated with fish length and size
      intervals (sub-adult, small and large adult), suggesting that larger and older
      fish bioaccumulated more mercury. A large excess of molar selenium in relation to
      mercury was observed.

PMID- 22617948
TI  - Detrimental effects of maternal lead exposure during pregnancy and lactation on
      molar development in the young rat.
AB  - The purpose of this animal study was to investigate the influence of maternal
      lead exposure during pregnancy and lactation on molar development in the
      offspring. Scanning electron microscopy revealed no significant differences in
      the molar morphology among the groups. However, in all the experimental groups,
      deep, wide cracks were found in the occlusal enamel. Further, the experimental
      groups had smaller molar diameters than the control group, lead exposure during
      lactation had a greater influence on the molar size in the offspring, and the
      groups with the higher dose of lead exposure during pregnancy and lactation had
      significantly smaller molar sizes than the groups that received the lower dose.
      The mesiodistal and buccolingual diameters of molars were measured as 3.10 +/-
      0.07 and 1.95 +/- 0.04 mm for control group, 2.97 +/- 0.08 and 1.94 +/- 0.01 mm
      for lactation group of low dose, 2.96 +/- 0.05 and 1.84 +/- 0.02 mm for lactation
      group of high dose, 3.09 +/- 0.06 and 1.94 +/- 0.04 mm for pregnancy group of low
      dose, and 3.02 +/- 0.06 and 1.85 +/- 0.06 mm for pregnancy group of high dose,
      respectively.

PMID- 22617949
TI  - The influence of filter mud compost and Tithonia diversifolia leaves on the
      dissipation of diuron in soils within the Nzoia River Drainage Basin, Kenya.
AB  - The aim of the study was to evaluate the environmental impact of filter mud
      compost and Tithonia diversifoila amendments on the dissipation of diuron in
      sugarcane cultivated soils. Filter mud compost is the by-product of sugarcane
      processing, while T. diversifoila is a common local plant that grows within the
      study region. The dissipation of diuron was significantly enhanced with DT(50) of
      15 and 16 days (p < 0.05) in soils amended with filter mud compost and T.
      diversifoila, respectively compared to 26 days in non-amended soils. Residues of
      0.93 %, 1.83 % and 5.40 % of the initial applied diuron were recorded at the end
      of the experiment in the three treatments, respectively. The residues of 3,4
      dichlorophenylmethylurea metabolite were 22.93 %, 25.92 % and 30.93 %, while
      10.19 %, 12.19 % and 15.46 % of 3,4-dichloroaniline metabolite remained in soil
      after 112 days in the three treatments, respectively.

PMID- 22617950
TI  - A critical assessment of storytelling: gene ontology categories and the
      importance of validating genomic scans.
AB  - In the age of whole-genome population genetics, so-called genomic scan studies
      often conclude with a long list of putatively selected loci. These lists are then
      further scrutinized to annotate these regions by gene function, corresponding
      biological processes, expression levels, or gene networks. Such annotations are
      often used to assess and/or verify the validity of the genome scan and the
      statistical methods that have been used to perform the analyses. Furthermore,
      these results are frequently considered to validate "true-positives" if the
      identified regions make biological sense a posteriori. Here, we show that this
      approach can be potentially misleading. By simulating neutral evolutionary
      histories, we demonstrate that it is possible not only to obtain an extremely
      high false-positive rate but also to make biological sense out of the false
      positives and construct a sensible biological narrative. Results are compared
      with a recent polymorphism data set from Drosophila melanogaster.

PMID- 22617951
TI  - The influence of rate heterogeneity among sites on the time dependence of
      molecular rates.
AB  - Molecular evolutionary rate estimates have been shown to depend on the time
      period over which they are estimated. Factors such as demographic processes,
      calibration errors, purifying selection, and the heterogeneity of substitution
      rates among sites (RHAS) are known to affect the accuracy with which rates of
      evolution are estimated. We use mathematical modeling and Bayesian analyses of
      simulated sequence alignments to explore how mutational hotspots can lead to time
      dependent rate estimates. Mathematical modeling shows that underestimation of
      molecular rates over increasing time scales is inevitable when RHAS is ignored.
      Although a gamma distribution is commonly used to model RHAS, we show that when
      the actual RHAS deviates from a gamma-like distribution, rates can either be
      under- or overestimated in a time-dependent manner. Simulations performed under
      different scenarios of RHAS confirm the mathematical modeling and demonstrate the
      impacts of time-dependent rates on estimates of divergence times. Most notably,
      erroneous rate estimates can have narrow credibility intervals, leading to false
      confidence in biased estimates of rates, and node ages. Surprisingly, large
      errors in estimates of overall molecular rate do not necessarily generate large
      errors in divergence time estimates. Finally, we illustrate the correlation
      between time-dependent rate patterns and differential saturation between quickly
      and slowly evolving sites. Our results suggest that data partitioning or simple
      nonparametric mixture models of RHAS significantly improve the accuracy with
      which node ages and substitution rates can be estimated.

PMID- 22617952
TI  - Ancient gene paralogy may mislead inference of plastid phylogeny.
AB  - Because of its ancient origin more than 1 billion years ago, the highly reduced
      plastid genomes of Plantae (e.g., plant chloroplasts) provide limited insights
      into the initial stages of endosymbiont genome reduction. The photosynthetic
      amoeba Paulinella provides a more useful model to study this process because its
      alpha-cyanobacterium-derived plastid originated ~60 Ma and the genome still
      contains ~1,000 genes. Here, we compared and contrasted features associated with
      genome reduction due to primary endosymbiosis in Paulinella plastids and in
      marine, free-living strains of the picocyanobacterium, Prochlorococcus. Both
      types of genomes show gene inactivation, concerted evolution, and contraction of
      gene families that impact highly conserved single-copy phylogenetic markers in
      the plastid such as psbA, psbC, and psbD. Our data suggest that these photosystem
      II genes may provide misleading phylogenetic signal because each of the
      constituent Plantae lineages has likely undergone a different, independent series
      of events that led to their reduction to a single copy. This issue is most
      problematic for resolving basal Plantae relationships when differential plastid
      gene loss was presumably ongoing, as we observe in Paulinella species. Our work
      uncovers a key, previously unappreciated aspect of organelle genome reduction and
      demonstrates "work-in-progress" models such as Paulinella to be critical to gain
      a fuller understanding of algal and plant genome evolution.

PMID- 22617954
TI  - Replacing and additive horizontal gene transfer in Streptococcus.
AB  - The prominent role of Horizontal Gene Transfer (HGT) in the evolution of bacteria
      is now well documented, but few studies have differentiated between evolutionary
      events that predominantly cause genes in one lineage to be replaced by homologs
      from another lineage ("replacing HGT") and events that result in the addition of
      substantial new genomic material ("additive HGT"). Here in, we make use of the
      distinct phylogenetic signatures of replacing and additive HGTs in a genome-wide
      study of the important human pathogen Streptococcus pyogenes (SPY) and its close
      relatives S. dysgalactiae subspecies equisimilis (SDE) and S. dysgalactiae
      subspecies dysgalactiae (SDD). Using recently developed statistical models and
      computational methods, we find evidence for abundant gene flow of both kinds
      within each of the SPY and SDE clades and of reduced levels of exchange between
      SPY and SDD. In addition, our analysis strongly supports a pronounced asymmetry
      in SPY-SDE gene flow, favoring the SPY-to-SDE direction. This finding is of
      particular interest in light of the recent increase in virulence of pathogenic
      SDE. We find much stronger evidence for SPY-SDE gene flow among replacing than
      among additive transfers, suggesting a primary influence from homologous
      recombination between co-occurring SPY and SDE cells in human hosts. Putative
      virulence genes are correlated with transfer events, but this correlation is
      found to be driven by additive, not replacing, HGTs. The genes affected by
      additive HGTs are enriched for functions having to do with transposition,
      recombination, and DNA integration, consistent with previous findings, whereas
      replacing HGTs seen to influence a more diverse set of genes. Additive transfers
      are also found to be associated with evidence of positive selection. These
      findings shed new light on the manner in which HGT has shaped pathogenic
      bacterial genomes.

PMID- 22617955
TI  - Calixarene-based supramolecular polymerization in solution.
AB  - Calixarenes are one kind of phenol-formaldehyde cyclic oligomers, discovered from
      the Bakelite process. Their intrinsic characteristics, including the unique
      structural scaffold, facile modification and adjustable inclusion property, show
      pronounced potential for supramolecular polymerization. In this tutorial review,
      we summarize the current stage of fabrication of calixarene-based supramolecular
      polymers. Three types of calixarene-based supramolecular polymers are,
      respectively, illustrated according to the different activities of calixarenes:
      (1) calixarene-based supramolecular polycaps, (2) supramolecular polymers with
      polymeric calixarene scaffolds where the cavities remain unexploited; (3)
      supramolecular polymers formed by the host-guest interactions offered by
      calixarene cavities. Furthermore, the stimuli-responsiveness and functions of
      calixarene-based supramolecular polymers are illustrated, which endow them with a
      broad range of potential applications as smart, self-healing materials and
      delivery carriers.

PMID- 22617957
TI  - Comparative transcriptomics of pathogenic and non-pathogenic Listeria species.
AB  - Listeria monocytogenes is a human, food-borne pathogen. Genomic comparisons
      between L. monocytogenes and Listeria innocua, a closely related non-pathogenic
      species, were pivotal in the identification of protein-coding genes essential for
      virulence. However, no comprehensive comparison has focused on the non-coding
      genome. We used strand-specific cDNA sequencing to produce genome-wide
      transcription start site maps for both organisms, and developed a publicly
      available integrative browser to visualize and analyze both transcriptomes in
      different growth conditions and genetic backgrounds. Our data revealed
      conservation across most transcripts, but significant divergence between the
      species in a subset of non-coding RNAs. In L. monocytogenes, we identified 113
      small RNAs (33 novel) and 70 antisense RNAs (53 novel), significantly increasing
      the repertoire of ncRNAs in this species. Remarkably, we identified a class of
      long antisense transcripts (lasRNAs) that overlap one gene while also serving as
      the 5' UTR of the adjacent divergent gene. Experimental evidence suggests that
      lasRNAs transcription inhibits expression of one operon while activating the
      expression of another. Such a lasRNA/operon structure, that we named 'excludon',
      might represent a novel form of regulation in bacteria.

PMID- 22617958
TI  - Multi-layered stochasticity and paracrine signal propagation shape the type-I
      interferon response.
AB  - The cellular recognition of viruses evokes the secretion of type-I interferons
      (IFNs) that induce an antiviral protective state. By live-cell imaging, we show
      that key steps of virus-induced signal transduction, IFN-beta expression, and
      induction of IFN-stimulated genes (ISGs) are stochastic events in individual
      cells. The heterogeneity in IFN production is of cellular-and not viral-origin,
      and temporal unpredictability of IFN-beta expression is largely due to cell
      intrinsic noise generated both upstream and downstream of the activation of
      nuclear factor-kappaB and IFN regulatory factor transcription factors. Subsequent
      ISG induction occurs as a stochastic all-or-nothing switch, where the responding
      cells are protected against virus replication. Mathematical modelling and
      experimental validation show that reliable antiviral protection in the face of
      multi-layered cellular stochasticity is achieved by paracrine response
      amplification. Achieving coherent responses through intercellular communication
      is likely to be a more widely used strategy by mammalian cells to cope with
      pervasive stochasticity in signalling and gene expression.

PMID- 22617953
TI  - Correlation between nuptial colors and visual sensitivities tuned by opsins leads
      to species richness in sympatric Lake Victoria cichlid fishes.
AB  - Reproductive isolation that prevents interspecific hybridization between closely
      related coexisting species maintains sympatric species diversity. One of the
      reproductive isolations is mate choice based on color signals (breeding color
      perceived by color vision). This is well known in several animal taxa, yet little
      is known about its genetic and molecular mechanism. Lake Victoria cichlid fishes
      are thought to be an example of sympatric species diversity. In the species
      inhabiting different light environments in rocky shore, speciation by sensory
      drive through color signals has been proposed by analyses of the long wavelength
      sensitive (LWS) opsin gene and the male nuptial coloration. However, the genetic
      and molecular mechanism of how diversity of sympatric species occurring in the
      same habitat is maintained remains unknown. To address this issue, we determined
      nucleotide sequences of eight opsins of six sympatric species collected from a
      sandy-muddy shore--an ideal model system for studying sympatric species. Among
      eight opsins, the LWS and RH1 alleles were diversified and one particular allele
      is dominant or fixed in each species, and we propose that this is due to natural
      selection. The functions of their LWS alleles were also diversified as shown by
      absorption measurements of reconstituted visual pigments. To analyze the
      relationship between nuptial coloration and the absorption of LWS pigments, we
      systematically evaluated and defined nuptial coloration. We showed that the
      coloration was species specific with respect to hue and significantly
      differentiated by the index values of hue (dominant wavelength: lambda(d)). The
      lambda(d) value of the male nuptial coloration correlated with the absorption of
      LWS pigments from all the species, suggesting that reproductive isolation through
      mate choice using color signals may prevent sympatric interspecific
      hybridization, thereby maintaining the species diversity in sympatric species in
      Lake Victoria.

PMID- 22617959
TI  - Transcription start site associated RNAs in bacteria.
AB  - Here, we report the genome-wide identification of small RNAs associated with
      transcription start sites (TSSs), termed tssRNAs, in Mycoplasma pneumoniae.
      tssRNAs were also found to be present in a different bacterial phyla, Escherichia
      coli. Similar to the recently identified promoter-associated tiny RNAs (tiRNAs)
      in eukaryotes, tssRNAs are associated with active promoters. Evidence suggests
      that these tssRNAs are distinct from previously described abortive transcription
      RNAs. ssRNAs have an average size of 45 bases and map exactly to the beginning of
      cognate full-length transcripts and to cryptic TSSs. Expression of bacterial
      tssRNAs requires factors other than the standard RNA polymerase holoenzyme. We
      have found that the RNA polymerase is halted at tssRNA positions in vivo, which
      may indicate that a pausing mechanism exists to prevent transcription in the
      absence of genes. These results suggest that small RNAs associated with TSSs
      could be a universal feature of bacterial transcription.

PMID- 22617960
TI  - Bio-functionalization of ligand-free upconverting lanthanide doped nanoparticles
      for bio-imaging and cell targeting.
AB  - We report on the functionalization of ligand-free NaGdF(4):Er(3+), Yb(3+)
      upconverting nanoparticles with heparin and basic fibroblast growth factor
      (bFGF). These upconverting nanoparticles are used to obtain high-contrast images
      of HeLa cells. These images reveal that the heparin-bFGF functionalized
      nanoparticles show specific binding to the cell membrane.

PMID- 22617994
TI  - The effects of aging on the intimal region of the human saphenous vein: insights
      from multimodal microscopy and quantitative image analysis.
AB  - We hypothesized that structural remodeling associated with advancing age occurs
      in human saphenous veins. To address this hypothesis, we have identified
      structural remodeling in human saphenous veins by applying histochemistry,
      fluorescence staining and quantitative image analysis to specifically assess
      intimal area, intimal cellularity and intimal collagen content and organization.
      Saphenous veins were collected from patients undergoing coronary artery bypass
      graft surgery. Area measurements and cellularity were quantified using the image
      analysis software Stereo Investigator, employing planimetry and counting frames,
      respectively. Collagen content and organization were quantified in MetaMorph
      image analysis software based on measurements of color (hue, saturation, and
      intensity) from polarized light images. Intimal area and cellularity showed no
      statistically significant increases with age; in contrast, total collagen content
      showed a significant decrease with advancing age. Furthermore, collagen fiber
      types also demonstrated a statistically significant alteration with age;
      increases in age resulted in decreases in larger collagen fibers. No significant
      changes in small collagen fibers were identified. These results raise the
      possibility that age-associated structural alterations in total collagen content,
      specifically collagen fiber size, could be a factor in the etiology of age
      associated venous diseases.

PMID- 22617993
TI  - Phosphorylation-dependent subcellular localization of the small heat shock
      proteins HspB1/Hsp25 and HspB5/alphaB-crystallin in cultured hippocampal neurons.
AB  - The so-called stress response involving upregulation of heat shock proteins
      (Hsps) is a powerful mechanism of cells to deal with harmful conditions to which
      they are exposed throughout life, such as hyperthermia, hypoxia or oxidative
      stress. To gain more information about the molecular targets by which HspB1
      (Hsp25) and HspB5 (alphaB-crystallin) might exert their neuroprotective effect we
      investigated the subcellular localization of unphosphorylated and phosphorylated
      HspB1 and B5 in neurons by immunocytochemistry and subcellular fractionation. In
      cultured hippocampal neurons, the unphosphorylated forms of both Hsps were
      localized in the perikaryon and nucleus, whereas the phosphorylated forms were
      recruited into neuronal processes. pHspB1-Ser15 and -Ser 86 were found within
      dendrites with a punctate distribution pattern partially colocalizing with the
      synaptic marker vGlut-1. pHspB5-Ser19 and -Ser45 localized to axons and dendrites
      with a filamentous-like staining pattern, whereas pHspB5-Ser59 was found in
      dendrites, especially along the plasma membrane and in spines. Biochemical
      analysis, i.e. subcellular fractionation of rat brain with subsequent Western
      blotting supported these localizations. These data show that in neurons HspB1 and
      B5 may have various molecular interaction partners at synapses, within dendrites
      and axons and that this interaction is likely to be regulated by phosphorylation.
      Stress-induced phosphorylation of HspB1 and B5 may lead to binding of these Hsps
      to their targets at synapses and neuronal processes which might provide one
      important mechanism of how they exert their neuroprotective effect.

PMID- 22618017
TI  - Trainee experiences of Child and Adolescent Psychiatry (CAP) training in Europe:
      2010-2011 survey of the European Federation of Psychiatric Trainees (EFPT) CAP
      working group.
AB  - The objective of this study was to investigate trainee experiences of Child and
      Adolescent Psychiatry (CAP) training across Europe in the following domains: (A)
      structure and organisation of training; (B) training quality and content; and (C)
      working conditions and recruitment. CAP trainee representatives were contacted
      via email across 34 countries in Europe using the European Federation of
      Psychiatric Trainees (EFPT) email list to complete a survey on CAP training in
      2010-2011. The European Union of Medical Specialties CAP group and trainees at
      the 2011 EFPT forum validated the survey data. Full surveys were submitted by 28
      of the 34 countries who have national CAP training schemes. These 28 countries
      are subject to the following further analysis. 7/28 countries (25 %) have a core
      common trunk in general psychiatry before trainees specialise in CAP. All
      countries bar one have national training standards for CAP. Training standards
      are implemented in practice to a variable extent. There is a CAP-specific
      theoretical education programme and national CAP conference in 25/28 countries
      (89 %). Supervision occurs at least weekly in 19/28 countries (68 %); emergency
      duty supervision is available in 18/28 (64 %) countries; educational supervision
      is available in 13/28 countries (46 %). Psychotherapy training is obligatory in
      19/28 countries (68 %). Research training is obligatory in 8/28 countries (29 %).
      Sub-specialty experience is extremely variable. Recruitment into CAP is a problem
      in 19/28 countries (68 %). Training experiences in CAP varies widely across
      European countries.

PMID- 22618018
TI  - Facile preparation of non-self-quenching fluorescent DNA strands with the degree
      of labeling up to the theoretic limit.
AB  - A new aggregation-induced emission (AIE) compound 1,1-dimethyl-2,5-bis[4
      (isothiocyanatemethyl)phenyl]-3,4-diphenylsilole (SITC) was synthesized and used
      to conjugate with aminoallyl-dUTP. The SITC-dUTP can be incorporated
      enzymatically into DNA strands with the degree of labeling (DOL) up to the
      theoretic limit.

PMID- 22618012
TI  - Choroid plexus: normal size criteria on neuroimaging.
AB  - PURPOSE: The lack of a well-recognized normal size criterion for the choroid
      plexus makes small or diffuse choroid plexus pathologies difficult to recognize.
      The purpose of this study was to determine the normal size of the choroid plexus
      in the pediatric population utilizing magnetic resonance imaging (MR) and
      ultrasound (US). As volume measurement across multiple slices is a laborious
      process, we wanted to propose a simple clinical tool that is easy to use,
      reproducible, and quick to obtain measurements. METHODS: This study
      retrospectively evaluated choroid plexus size in 90 children between the ages of
      0 and 16. To determine the choroid plexus thickness, a total of 97 studies (71
      MRIs and 26 Ultrasounds) were reviewed, from children without any signs of
      choroid plexus pathology; 6 measurements were taken from MR studies, and 3
      measurements were taken from US studies. Averages and ranges of choroid plexus
      thickness were computed across age groups and gender. RESULTS: Across all ages,
      the mean choroid plexus thickness in the lateral ventricles was found to be 3.4,
      3.3, and 3.1 mm in the axial, coronal, and sagittal views; 3.2 mm in the temporal
      horns; 2.5 mm in the fourth ventricle with the lateral limb of the choroid plexus
      in the fourth ventricle measuring 11.3 mm in length. No trends were observed with
      respect to age subgroups or gender. CONCLUSION: Choroid plexus thickness on
      average was 3.2 mm in the lateral ventricles and 2.5 mm in the fourth ventricle.

PMID- 22617995
TI  - Chondroitin sulphate and heparan sulphate sulphation motifs and their
      proteoglycans are involved in articular cartilage formation during human foetal
      knee joint development.
AB  - Novel sulphation motifs within the glycosaminoglycan chain structure of
      chondroitin sulphate (CS) containing proteoglycans (PGs) are associated with
      sites of growth, differentiation and repair in many biological systems and there
      is compelling evidence that they function as molecular recognition sites that are
      involved in the binding, sequestration or presentation of soluble signalling
      molecules (e.g. morphogens, growth factors and cytokines). Here, using monoclonal
      antibodies 3B3(-), 4C3 and 7D4, we examine the distribution of native CS
      sulphation motifs within the developing connective tissues of the human foetal
      knee joint, both during and after joint cavitation. We show that the CS motifs
      have broad, overlapping distributions within the differentiating connective
      tissues before the joint has fully cavitated; however, after cavitation, they all
      localise very specifically to the presumptive articular cartilage tissue.
      Comparisons with the labelling patterns of heparan sulphate (HS), HS-PGs
      (perlecan, syndecan-4 and glypican-6) and FGF-2, molecules with known signalling
      roles in development, indicate that these also become localised to the future
      articular cartilage tissue after joint cavitation. Furthermore, they display
      interesting, overlapping distributions with the CS motifs, reflective of early
      tissue zonation. The overlapping expression patterns of these molecules at this
      site suggests they are involved, or co-participate, in early morphogenetic events
      underlying articular cartilage formation; thus having potential clinical
      relevance to mechanisms involved in its repair/regeneration. We propose that
      these CS sulphation motifs are involved in modulating the signalling gradients
      responsible for the cellular behaviours (proliferation, differentiation, matrix
      turnover) that shape the zonal tissue architecture present in mature articular
      cartilage.

PMID- 22618019
TI  - Fluorescent probe for detection of bacteria: conformational trigger upon
      bacterial reduction of an azo bridge.
AB  - Using biomimetic chemical reduction or Clostridium perfringens cell extract
      containing azoreductase, the dimer-fluorescent probe 2,4-O-bisdansyl-6,7
      diazabicyclooct-6-ene, which possesses a conformationally constrained cis-azo
      bridge, is reduced to the tetra-equatorial 2,4-O-bisdansyl-cyclohexyl-3,5
      bisammonium salt which exhibits fluorescence indicative of a dansyl monomer.

PMID- 22618021
TI  - Trace determination of dichlorvos in environmental samples by room temperature
      ionic liquid-based dispersive liquid-phase microextraction combined with HPLC.
AB  - Using 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6]) room
      temperature ionic liquid (RTIL) as extraction solvent, tetrahydrofuran (THF) as
      disperser solvent, the organophosphorus pesticide dichlorvos in water was
      determined by dispersive liquid-liquid microextraction (DLLME) combined with high
      performance liquid chromatography. Factors affecting RTIL-DLLME (type of
      disperser solvent, amount of RTIL, volume of disperser solvent, percentage of
      NaCl and volume and pH of water sample) were optimized by the single-factor
      method, obtaining the most favorable results when using 65 uL of [BMIM][PF6] and
      260 uL of THF to extract the compound from an 8-mL water sample at pH 5.0
      containing 25% (w/v) of NaCl. Under these optimum conditions, an enrichment
      factor of 215-fold was obtained. The calibration curves were linear in the
      concentration range of 2-1,000 ug/L. The limit of detection calculated at a
      signal-to-noise ratio of 3 was 0.2 ug/L. The relative standard deviations (RSD)
      for six replicate experiments at 20, 100 and 200 ug/L concentration levels were
      1.8%, 1.3% and 1.3 %, respectively. Then the proposed method was applied to the
      analysis of three different water sample sources (tap, farm and rain water) and
      the relative recoveries and RSD of spiked water samples were 95.6-102.4% and 0.6
      3.1%, respectively, at three different concentration levels of 20, 100 and 200
      ug/L.

PMID- 22618020
TI  - Liver fibrosis and hepatocyte apoptosis are attenuated by GKT137831, a novel
      NOX4/NOX1 inhibitor in vivo.
AB  - Reactive oxygen species (ROS) play a key role in chronic liver injury and
      fibrosis. Homologs of NADPH oxidases (NOXs) are major sources of ROS, but the
      exact role of the individual homologs in liver disease is unknown. Our goal was
      to determine the role of NOX4 in liver fibrosis induced by bile duct ligation
      (BDL) with the aid of the pharmacological inhibitor GKT137831, and genetic
      deletion of NOX4 in mice. GKT137831 was either applied for the full term of BDL
      (preventive arm) or started at 10 day postoperatively (therapeutic arm). Primary
      hepatic stellate cells (HSC) from control mice with and without BDL were analyzed
      and the effect of NOX4 inhibition on HSC activation was also studied. FasL or
      TNFalpha/actinomycin D-induced apoptosis was studied in wild-type and NOX4(-/-)
      hepatocytes. NOX4 was upregulated by a TGF-beta/Smad3-dependent mechanism in HSC.
      Downregulation of NOX4 decreased ROS production and the activation of NOX4(-/-)
      HSC was attenuated. NOX4(-/-) hepatocytes were more resistant to FasL or
      TNFalpha/actinomycin D-induced apoptosis. Similarly, after pharmacological NOX4
      inhibition, ROS production, the expression of fibrogenic markers, and hepatocyte
      apoptosis were reduced. NOX4 was expressed in human livers with stage 2-3
      autoimmune hepatitis. Fibrosis was attenuated by the genetic deletion of NOX4.
      BDL mice gavaged with GKT137831 in the preventive or the therapeutic arm
      displayed less ROS production, significantly attenuated fibrosis, and decreased
      hepatocyte apoptosis. In conclusion, NOX4 plays a key role in liver fibrosis.
      GKT137831 is a potent inhibitor of fibrosis and hepatocyte apoptosis; therefore,
      it is a promising therapeutic agent for future translational studies.

PMID- 22618022
TI  - Analysis of repaglinide enantiomers in pharmaceutical formulations by capillary
      electrophoresis using 2,6-di-o-methyl-beta-cyclodextrin as a chiral selector.
AB  - This study used the general applicability of 2,6-didi-o-methyl-beta-cyclodextrin
      (DM-beta-CD) as the chiral selector in capillary electrophoresis for fast and
      efficient chiral separation of repaglinide enantiomers. A systematic study of the
      parameters affecting separation was performed with UV detection at 243 nm. The
      optimum conditions were determined to be 1.25% (w/v) DM-beta-CD in 20 mM sodium
      phosphate (pH 2.5) as the running buffer and separation voltage at 20 kV. DM-beta
      CD had the best enantiomer resolution properties under the tested conditions,
      whereas other beta-cyclodextrins showed inferior performances or no performance.
      The proposed method had a linear calibration curve in the concentration range of
      12.5-400 ug/mL. The limit of detection was 100 ng/mL. The intra-day and inter-day
      precisions were 2.8 and 3.2%, respectively. Recoveries of 97.9-100.9% were
      obtained. The proposed method was fast and convenient, and was determined to be
      efficient for separating enantiomers and applicable for analyzing repaglinide
      enantiomers in quality control of pharmaceutical production.

PMID- 22618023
TI  - Using the interactive systems framework to support a quality improvement approach
      to dissemination of evidence-based strategies to promote early detection of
      breast cancer: planning a comprehensive dynamic trial.
AB  - Dissemination efforts must optimize interventions for new settings and
      populations. As such, dissemination research should incorporate principles of
      quality improvement. Comprehensive Dynamic Trial (CDT) designs examine how
      information gained during dissemination may be used to modify interventions and
      improve performance. Although CDT may offer distinct advantages over static
      designs, organizing the many necessary roles and activities is a significant
      challenge. In this article, we discuss use of the Interactive Systems Framework
      for Dissemination and Implementation to systematically implement a CDT.
      Specifically, we describe "Bronx ACCESS", a program designed to disseminate
      evidence-based strategies to promote adherence to mammography guidelines. In
      Bronx ACCESS, the Intervention Delivery System will elicit information needed to
      adapt strategies to specific settings and circumstances. The Intervention
      Synthesis and Translation System will use this information to test changes to
      strategies through "embedded experiments". The Intervention Support System will
      build local capacities found to be necessary for intervention
      institutionalization. Simulation modeling will be used to integrate findings
      across systems. Results will inform on-going policy debate about interventions
      needed to promote population-level screening. More generally, this project is
      intended to advance understanding of research paradigms necessary to study
      dissemination.

PMID- 22618024
TI  - Ready, willing, and able: developing a support system to promote implementation
      of school-based prevention programs.
AB  - While the number and scope of evidence-based health, education, and mental health
      services continues to grow, the movement of these practices into schools and
      other practice settings remains a complex and haphazard process. The purpose of
      this paper is to describe and present initial support for a prevention support
      system designed to promote high-quality implementation of whole school prevention
      initiatives in elementary and middle schools. The function and strategies of a
      school-based prevention support system are discussed, including key structures
      and activities undertaken to identify, select, and provide technical assistance
      to school personnel. Data collected over a 5 year period are presented, including
      evidence of successful implementation support for 5 different evidence-based
      programs implemented with fidelity at 12 schools and preliminary evidence of goal
      attainment. Findings suggest the ongoing collection of information related to
      organizational readiness assists in the adoption and implementation of effective
      practices and initiatives and provide valuable insight into the development of
      results-oriented approaches to prevention service delivery. Problems, progress,
      and lessons learned through this process are discussed to frame future research
      and action steps for this school-based prevention support system.

PMID- 22618025
TI  - Practical implementation science: developing and piloting the quality
      implementation tool.
AB  - According to the Interactive Systems Framework for Dissemination and
      Implementation, implementation is a major mechanism and concern in bridging
      research and practice. The growing number of implementation frameworks need to be
      synthesized and translated so that the science and practice of quality
      implementation can be furthered. In this article, we: (1) use the synthesis of
      frameworks developed by Meyers et al. (Am J Commun Psychol, 2012) and translate
      the results into a practical implementation science tool to use for improving
      quality of implementation (i.e., the Quality Implementation Tool; QIT), and (2)
      present some of the benefits and limitations of the tool by describing how the
      QIT was implemented in two different pilot projects. We discuss how the QIT can
      be used to guide collaborative planning, monitoring, and evaluation of how an
      innovation is implemented.

PMID- 22618026
TI  - Electrospinning versus fibre production methods: from specifics to technological
      convergence.
AB  - Academic and industrial research on nanofibres is an area of increasing global
      interest, as seen in the continuously multiplying number of research papers and
      patents and the broadening range of chemical, medical, electrical and
      environmental applications. This in turn expands the size of the market
      opportunity and is reflected in the significant rise of entrepreneurial
      activities and investments in the field. Electrospinning is probably the most
      researched top-down method to form nanofibres from a remarkable range of organic
      and inorganic materials. It is well known and discussed in many comprehensive
      studies, so why this review? As we read about yet another "novel" method
      producing multifunctional nanomaterials in grams or milligrams in the laboratory,
      there is hardly any research addressing how these methods can be safely,
      consistently and cost-effectively up-scaled. Despite two decades of governmental
      and private investment, the productivity of nanofibre forming methods is still
      struggling to meet the increasing demand. This hinders the further integration of
      nanofibres into practical large-scale applications and limits current uses to
      niche-markets. Looking into history, this large gap between supply and demand of
      synthetic fibres was seen and addressed in conventional textile production a
      century ago. The remarkable achievement was accomplished via extensive
      collaborative research between academia and industry, applying ingenious
      solutions and technological convergence from polymer chemistry, physical
      chemistry, materials science and engineering disciplines. Looking into the
      present, current advances in electrospinning and nanofibre production are showing
      similar interdisciplinary technological convergence, and knowledge of industrial
      textile processing is being combined with new developments in nanofibre forming
      methods. Moreover, many important parameters in electrospinning and nanofibre
      spinning methods overlap parameters extensively studied in industrial fibre
      processing. Thus, this review combines interdisciplinary knowledge from the
      academia and industry to facilitate technological convergence and offers insight
      for upscaling electrospinning and nanofibre production. It will examine advances
      in electrospinning within a framework of large-scale fibre production as well as
      alternative nanofibre forming methods, providing a comprehensive comparison of
      conventional and contemporary fibre forming technologies. This study intends to
      stimulate interest in addressing the issue of scale-up alongside novel
      developments and applications in nanofibre research.

PMID- 22618027
TI  - To waste or not to waste - food?

PMID- 22618028
TI  - Yes-associated protein 1 is activated and functions as an oncogene in
      meningiomas.
AB  - The Hippo signaling pathway is functionally conserved in Drosophila melanogaster
      and mammals, and its proposed function is to control tissue homeostasis by
      regulating cell proliferation and apoptosis. The core components are composed of
      a kinase cascade that culminates with the phosphorylation and inhibition of Yes
      associated protein 1 (YAP1). Phospho-YAP1 is retained in the cytoplasm. In the
      absence of Hippo signaling, YAP1 translocates to the nucleus, associates with co
      activators TEAD1-4, and functions as a transcriptional factor promoting the
      expression of key target genes. Components of the Hippo pathway are mutated in
      human cancers, and deregulation of this pathway plays a role in tumorigenesis.
      Loss of the NF2 tumor suppressor gene is the most common genetic alteration in
      meningiomas, and the NF2 gene product, Merlin, acts upstream of the Hippo
      pathway. Here, we show that primary meningioma tumors have high nuclear
      expression of YAP1. In meningioma cells, Merlin expression is associated with
      phosphorylation of YAP1. Using an siRNA transient knockdown of YAP1 in NF2-mutant
      meningioma cells, we show that suppression of YAP1 impaired cell proliferation
      and migration. Conversely, YAP1 overexpression led to a strong augment of cell
      proliferation and anchorage-independent growth and restriction of cisplatin
      induced apoptosis. In addition, expression of YAP1 in nontransformed arachnoidal
      cells led to the development of tumors in nude mice. Together, these findings
      suggest that in meningiomas, deregulation of the Hippo pathway is largely
      observed in primary tumors and that YAP1 functions as an oncogene promoting
      meningioma tumorigenesis.

PMID- 22618029
TI  - Geographic prioritization of distributing pandemic influenza vaccines.
AB  - Pandemic influenza is an international public health concern. In light of the
      persistent threat of H5N1 avian influenza and the recent pandemic of A/H1N1swine
      influenza outbreak, public health agencies around the globe are continuously
      revising their preparedness plans. The A/H1N1 pandemic of 2009 demonstrated that
      influenza activity and severity might vary considerably among age groups and
      locations, and the distribution of an effective influenza vaccine may be
      significantly delayed and staggered. Thus, pandemic influenza vaccine
      distribution policies should be tailored to the demographic and spatial
      structures of communities. Here, we introduce a bi-criteria decision-making
      framework for vaccine distribution policies that is based on a geospatial and
      demographically-structured model of pandemic influenza transmission within and
      between counties of Arizona in the Unites States. Based on data from the 2009
      2010 H1N1 pandemic, the policy predicted to reduce overall attack rate most
      effectively is prioritizing counties expected to experience the latest epidemic
      waves (a policy that may be politically untenable). However, when we consider
      reductions in both the attack rate and the waiting period for those seeking
      vaccines, the widely adopted pro rata policy (distributing according to
      population size) is also predicted to be an effective strategy.

PMID- 22618057
TI  - Timing matters: the underappreciated role of temperature ramp rate for shape
      control and reproducibility of quantum dot synthesis.
AB  - Understanding the coupled kinetic and thermodynamics factors governing colloidal
      nanocrystals nucleation and growth are critical factors in the predictable and
      reproducible synthesis of advanced nanomaterials. We show that the temporal
      temperature profile is decisive in tuning the particle shape from pseudo
      spherical to monodisperse cubes. The shape of the nanocrystals was characterized
      by transmission electron microscopy and X-ray diffraction. We introduce a
      mechanism for the shape controlled synthesis in the context of temperature
      dependent nucleation and growth and provide experimental evidence to support it.

PMID- 22618080
TI  - Stimuli-responsive supramolecular polymeric materials.
AB  - Supramolecular materials, dynamic materials by nature, are defined as materials
      whose components are bridged via reversible connections and undergo spontaneous
      and continuous assembly/disassembly processes under specific conditions. On
      account of the dynamic and reversible nature of noncovalent interactions,
      supramolecular polymers have the ability to adapt to their environment and
      possess a wide range of intriguing properties, such as degradability, shape
      memory, and self-healing, making them unique candidates for supramolecular
      materials. In this critical review, we address recent developments in
      supramolecular polymeric materials, which can respond to appropriate external
      stimuli at the fundamental level due to the existence of noncovalent interactions
      of the building blocks.

PMID- 22618079
TI  - Smoking and HIV: prevalence, health risks, and cessation strategies.
AB  - Health hazards due to smoking may undermine benefits of HIV treatment on
      morbidity and mortality. Over 40% of persons with HIV are current smokers. Health
      risks of smoking include increases in some HIV-associated infections,
      cardiovascular disease, some cancers, bacterial pneumonia and other lung disease,
      and overall mortality. Proven strategies for smoking cessation include various
      counseling approaches, nicotine replacement therapy and other pharmacotherapy;
      approaches may need to be individualized to address specific client needs and
      comorbidities. HIV clinicians and other service providers can have an influential
      role in screening their patients for smoking and promoting cessation programs to
      improve health.

PMID- 22618081
TI  - Color and antioxidant characteristics of some fresh fig (Ficus carica L.)
      genotypes from northeastern Turkey.
AB  - Fruit skin color, total phenolics, total anthocyanins, soluble solids content,
      titratable acidity and total antioxidant capacity in fresh fruits of a number of
      local and well-known fig (Ficus carica L.) genotypes and cultivars grown in
      northeastern Turkey were determined. TEAC (Trolox equivalent antioxidant
      capacity) and FRAP (ferric reducing antioxidant power) assays were used to
      determine total antioxidant capacity. Fruit skin color of genotypes were found to
      be very diverse, i.e., light green, light purple, purple, dark purple and black.
      The content of total phenolics, soluble solids content (SSC) and titratable
      acidity greatly varied in the range from 24 to 237 mg of gallic acid equivalent
      per 100 g fresh weight, 18.60 to 26.30 % and 0.16 to 0.47 % in local genotypes
      and studied cultivars. In general, total antioxidant capacities determined by two
      methods expressed higher values in the local fig genotypes compared with the
      cultivars. The results suggested that genotype is the main factor that determines
      difference in the composition of bioactive compounds in figs and provide
      information on putative health benefits locally grown genotypes.

PMID- 22618082
TI  - Tuning glycosidase inhibition through aglycone interactions: pharmacological
      chaperones for Fabry disease and GM1 gangliosidosis.
AB  - Competitive inhibitors of either alpha-galactosidase (alpha-Gal) or beta
      galactosidase (beta-Gal) with high affinity and selectivity have been accessed by
      exploiting aglycone interactions with conformationally locked sp(2)-iminosugars.
      Selected compounds were profiled as potent pharmacological chaperones for mutant
      lysosomal alpha- and beta-Gal associated with Fabry disease and GM(1)
      gangliosidosis.

PMID- 22618090
TI  - Early repair of open abdomen with a tailored two-component mesh and conditioning
      vacuum packing: a safe alternative to the planned giant ventral hernia.
AB  - PURPOSE: Once open abdomen therapy has succeeded, the problem of closing the
      abdominal wall must be addressed. We present a new four-stage procedure involving
      the application of a two-component mesh and vacuum conditioning for abdominal
      wall closure of even large defects. The aim is to prevent the development of a
      giant ventral hernia and the eventual need for the repair of the abdominal wall.
      METHODS: Nineteen of 62 patients treated by open abdomen over a two-year period
      could not receive primary abdominal wall closure. To achieve closure in these
      patients, we applied the following four-stage procedure: stage 1: abdominal
      damage control and conditioning of the abdominal wall; stage 2: attachment of a
      tailored two-component mesh of polyglycolic acid (PGA) and large pore
      polypropylene (PP) in intraperitoneal position (IPOM) plus placement of a vacuum
      bandage; stage 3: vacuum therapy for 3-4 weeks to allow granulation of the mesh
      and optimization of dermatotraction; stage 4: final skin suture. During stage 3,
      eligible patients were weaned from respirator and mobilized. RESULTS: The
      abdominal wall gap in the 19 patients ranged in size from 240 cm(2) to more than
      900 cm(2). An average of 3.44 vacuum dressing changes over 19 days were required
      to achieve 60-100 % granulation of the surface area, so final skin suture could
      be made. Already in stage 3, 14 patients (73.68 %) could be weaned from
      respirator an average of 6.78 days after placement of the two-component mesh; 6
      patients (31.57 %) could be mobilized on the edge of the bed and/or to a bedside
      chair after an average of 13 days. No mesh-related hematomas, seromas, or
      intestinal fistulas were observed. CONCLUSION: The four-stage procedure presented
      here is a viable option for achieving abdominal wall closure in patients treated
      with open abdomen, enabling us to avoid the development of planned giant ventral
      hernias. It has few complications and has the special advantage of allowing
      mobilization of the patients before final skin closure. Long-term course in a
      large number of patients must still confirm this result.

PMID- 22618091
TI  - Traumatic aortic injury score (TRAINS): an easy and simple score for early
      detection of traumatic aortic injuries in major trauma patients with associated
      blunt chest trauma.
AB  - PURPOSE: To develop a risk score based on physical examination and chest X-ray
      findings to rapidly identify major trauma patients at risk of acute traumatic
      aortic injury (ATAI). METHODS: A multicenter retrospective study was conducted
      with 640 major trauma patients with associated blunt chest trauma classified into
      ATAI (aortic injury) and NATAI (no aortic injury) groups. The score data set
      included 76 consecutive ATAI and 304 NATAI patients from a single center, whereas
      the validation data set included 52 consecutive ATAI and 208 NATAI patients from
      three independent institutions. Bivariate analysis identified variables
      potentially influencing the presentation of aortic injury. Confirmed variables by
      logistic regression were assigned a score according to their corresponding beta
      coefficient which was rounded to the closest integer value (1-4). RESULTS:
      Predictors of aortic injury included widened mediastinum, hypotension less than
      90 mmHg, long bone fracture, pulmonary contusion, left scapula fracture,
      hemothorax, and pelvic fracture. Area under receiver operating characteristic
      curve was 0.96. In the score data set, sensitivity was 93.42 %, specificity 85.85
      %, Youden's index 0.79, positive likelihood ratio 6.60, and negative likelihood
      ratio 0.08. In the validation data set, sensitivity was 92.31 % and specificity
      85.1 %. CONCLUSIONS: Given the relative infrequency of traumatic aortic injury,
      which often leads to missed or delayed diagnosis, application of our score has
      the potential to draw necessary clinical attention to the possibility of aortic
      injury, thus providing the chance of a prompt specific diagnostic and therapeutic
      management.

PMID- 22618092
TI  - Preoperative hypoalbuminemia is a major risk factor for acute kidney injury
      following off-pump coronary artery bypass surgery.
AB  - PURPOSE: To investigate the association between preoperative low serum albumin
      level and acute kidney injury (AKI) after off-pump coronary artery bypass surgery
      (OPCAB) METHOD: We assessed preoperative and perioperative risk factors, and
      preoperative serum albumin concentration in 1,182 consecutive adult patients with
      preoperative normal renal function who underwent OPCAB surgery. Each patient was
      categorized by maximal Acute Kidney Injury Network (AKIN) criteria based on
      creatinine changes within the first 48 h after OPCAB. Logistic regression and
      propensity analyses were performed to evaluate the association between
      preoperative low serum albumin level and postoperative AKI. RESULTS: Of the 1,182
      patients, 334 (28.3%) developed AKI. Risk factors for AKI were old age, diabetes
      mellitus, maximal cardiovascular component of the sequential organ failure
      assessment score, perioperative transfusion, and postoperative C-reactive protein
      concentration. The risk of AKI was negatively correlated with the volume of
      crystalloid infused during surgery. A preoperative serum albumin level of <4.0
      g/dl was independently associated Ith postoperative AKI [multivariable logistic
      analysis: odds ratio (OR) 1.83, 95 % confidence interval (CI) 1.27-2.64; P =
      0.001; propensity analysis: OR 1.62, 95 % CI 1.12-2.35; P = 0.011). AKI was
      associated with prolonged stay in the intensive care unit and hospital and a high
      mortality rate. CONCLUSIONS: Preoperative low serum albumin level is an
      independent risk factor for AKI, and postoperative AKI is associated with poor
      outcomes after OPCAB in patients with preoperative normal renal function.

PMID- 22618093
TI  - A qualitative study of resilience and posttraumatic stress disorder in United
      States ICU nurses.
AB  - PURPOSE: Intensive care unit (ICU) nurses are at increased risk of developing
      psychological problems including posttraumatic stress disorder (PTSD). However,
      there are resilient individuals who thrive and remain employed as ICU nurses for
      many years. The purpose of this study was to identify mechanisms employed by
      highly resilient ICU nurses to develop preventative therapies to obviate the
      development of PTSD in ICU nurses. METHODS: Qualitative study using semi
      structured telephone interviews with randomly selected ICU nurses in the USA.
      Purposive sampling was used to identify ICU nurses who were highly resilient,
      based on the Connor-Davidson Resilience Scale and those with a diagnosis of PTSD,
      based on the posttraumatic diagnostic scale. New interviews were conducted until
      we reached thematic saturation. RESULTS: Thirteen highly resilient nurses and
      fourteen nurses with PTSD were interviewed (n = 27). A constructivist
      epistemological framework was used for data analysis. Differences were identified
      in four major domains: worldview, social network, cognitive flexibility, and self
      care/balance. Highly resilient nurses identified spirituality, a supportive
      social network, optimism, and having a resilient role model as characteristics
      used to cope with stress in their work environment. ICU nurses with a diagnosis
      of PTSD possessed several unhealthy characteristics including a poor social
      network, lack of identification with a role model, disruptive thoughts, regret,
      and lost optimism. CONCLUSION: Highly resilient ICU nurses utilize positive
      coping skills and psychological characteristics that allow them to continue
      working in the stressful ICU environment. These characteristics and skills may be
      used to develop target therapies to prevent PTSD in ICU nurses.

PMID- 22618094
TI  - Impact of volume guarantee on synchronized ventilation in preterm infants: a
      randomized controlled trial.
AB  - PURPOSE: The aim of this randomized controlled trial was to assess whether the
      addition of volume guarantee (VG) to triggered ventilation decreases the duration
      of ventilation in very low birth weight (VLBW) infants with respiratory distress
      syndrome (RDS). METHODS: Infants were randomized into two groups to initially
      receive either assist/control (A/C) or A/C plus VG ventilation and then weaned
      with synchronized intermittent mandatory ventilation (SIMV) or SIMV plus VG.
      RESULTS: Forty-five infants were included in the study. The demographic and
      clinical characteristics, values of tidal volume (VT), peak inspiratory pressure
      (PIP), fraction of inspired oxygen, carbon dioxide tension, and pH were similar
      for all participating infants initially. During the follow-up, the VT levels were
      more stable, and the PIP levels were significantly decreasing in the VG group.
      Although the duration of ventilation was shorter in the VG group, this trend was
      not statistically significant. The incidences of death and bronchopulmonary
      dysplasia (BPD) were not significantly different, but the combined outcome of
      death or BPD was lower in the VG group. Although the VG group experienced less
      frequent BPD, periventricular leukomalacia, and intraventricular hemorrhage,
      these differences were not statistically different. CONCLUSION: The VG option,
      when combined with A/C (in the acute phase of RDS) and SIMV (in the weaning),
      reduced VT variability, and may have shortened the duration of ventilation in
      VLBW infants. Overall mortality and BPD rates did not change, but their combined
      outcome was significantly improved in infants treated with VG modes as compared
      to those treated with synchronized pressure-limited modes alone.

PMID- 22618095
TI  - A rare cause of cardiogenic shock.

PMID- 22618096
TI  - Safety of nicotine replacement therapy in critically ill smokers: a retrospective
      cohort study.
AB  - PURPOSE: Nicotine replacement therapy (NRT) has been used to ameliorate nicotine
      withdrawal in the intensive care unit (ICU). Previous cohort studies have
      suggested an increased mortality with NRT use: methodological problems may call
      into question the validity of these findings. We undertook a retrospective cohort
      study to determine if NRT use was associated with adverse outcomes. METHODS: This
      retrospective cohort study was conducted in a 30-bed, university affiliated,
      teaching hospital ICU. RESULTS: We identified 423 smokers admitted over 2 years,
      of whom 73 received transdermal NRT. Cox proportional hazard regression models,
      with NRT modelled as a time-varying covariate, were used to test the hypothesis
      that NRT was associated with an altered ICU or hospital mortality. A second
      analysis utilized propensity scores. The unadjusted ICU and hospital mortalities
      were lower for the NRT group; although both differences were non-significant. The
      Cox models showed that, after adjustment for APACHE risk, age, sex and alcohol
      use, risk associated with NRT administration was not statistically different than
      non-administration for both ICU (hazard ratio 0.50, [95 % CI 0.20-1.24], p =
      0.14) and hospital (hazard ratio 0.95, [95 % CI 0.52-1.75], p = 0.88) mortality.
      Similar findings occurred with the propensity matched analysis. CONCLUSION: We
      were unable to demonstrate any harm associated with NRT, with the ICU model
      actually trending towards benefit. We conclude that a randomised, blinded,
      placebo controlled trial is required to assess adequately the safety and efficacy
      of NRT as a treatment in critically ill smokers.

PMID- 22618119
TI  - On the relationship between automatic attitudes and self-reported sexual assault
      in men.
AB  - Research and theory suggest rape supportive attitudes are important predictors of
      sexual assault; yet, to date, rape supportive attitudes have been assessed
      through self-report measures that are methodologically and theoretically limited.
      To address these limitations, the objectives of the current project were to: (1)
      develop a novel implicit rape attitude assessment that captures automatic
      attitudes about rape and does not rely on self-reports, and (2) examine the
      association between automatic rape attitudes and sexual assault perpetration. We
      predicted that automatic rape attitudes would be a significant unique predictor
      of sexual assault even when self-reported rape attitudes (i.e., rape myth
      acceptance and hostility toward women) were controlled. We tested the
      generalizability of this prediction in two independent samples: a sample of
      undergraduate college men (n = 75, M age = 19.3 years) and a sample of men from
      the community (n = 50, M age = 35.9 years). We found the novel implicit rape
      attitude assessment was significantly associated with the frequency of sexual
      assault perpetration in both samples and contributed unique variance in
      explaining sexual assault beyond rape myth acceptance and hostility toward women.
      We discuss the ways in which future research on automatic rape attitudes may
      significantly advance measurement and theory aimed at understanding and
      preventing sexual assault. 

PMID- 22618120
TI  - Fabrication and magnetic properties of Ni nanowire arrays with ultrahigh axial
      squareness.
AB  - Poly- and single-crystalline Ni nanowire arrays showing ultrahigh axial
      squareness are fabricated by direct-current electrodeposition in pores of anodic
      aluminum oxide templates. High voltage is shown to be the key in order for Ni
      nanowires to have a (220) preferred orientation. 2-Dimensional nucleation theory
      is used to understand the growth of the nanowires. Based on the structure and
      growth analyses, the magnetic properties of different kinds of nanowires are
      explained. 

PMID- 22618126
TI  - Critical care of the potential organ donor.
AB  - Organ transplantation represents one of the great success stories of 20th century
      medicine. However, its continued success is greatly limited by the shortage of
      donor organs. This has led to an increased focus within the critical care
      community on optimal identification and management of the potential organ donor.
      The multi-organ donor can represent one of the most complex intensive care
      patients, with numerous competing physiological priorities. However, appropriate
      management of the donor not only increases the number of organs that can be
      successfully donated but has long-term implications for the outcomes of multiple
      recipients. This review outlines current understandings of the physiological
      derangements seen in the organ donor and evaluates the available evidence for
      management strategies designed to optimize donation potential and organ recovery.
      Finally, emerging management strategies for the potential donor are discussed
      within the current ethical and legal frameworks permitting donation after both
      brain and circulatory death.

PMID- 22618128
TI  - Diagnosing and monitoring diabetic macular edema: structural and functional
      tests.
AB  - Diabetic macular edema remains a major cause of visual impairment in adults
      despite the use of intensive glycemic control, photocoagulation therapy and new
      intravitreal drugs in the treatment of this disease. Although early diagnosis and
      treatment lead to better results, we still have patients who become legally
      blind. Therefore, better structural and functional characterization of this
      disease is necessary in order to customize treatment. 

PMID- 22618127
TI  - Genetics of epilepsy and relevance to current practice.
AB  - Genetic factors are likely to play a major role in many epileptic conditions,
      spanning from classical idiopathic (genetic) generalized epilepsies to epileptic
      encephalopathies and focal epilepsies. In this review we describe the genetic
      advances in progressive myoclonus epilepsies, which are strictly monogenic
      disorders, genetic generalized epilepsies, mostly exhibiting complex genetic
      inheritance, and SCN1A-related phenotypes, namely genetic generalized epilepsy
      with febrile seizure plus and Dravet syndrome. Particular attention is devoted to
      a form of familial focal epilepsies, autosomal-dominant lateral temporal
      epilepsy, which is a model of non-ion genetic epilepsies. This condition is
      associated with mutations of the LGI1 gene, whose protein is secreted from the
      neurons and exerts its action on a number of targets, influencing cortical
      development and neuronal maturation.

PMID- 22618129
TI  - Corneal changes in ectrodactyly-ectodermal dysplasia-cleft lip and palate
      syndrome: case series and literature review.
AB  - The aim of this study is to describe the corneal changes in three unrelated
      patients with ectrodactyly-ectodermal dysplasia-cleft lip and palate (EEC)
      syndrome and review the literature on the possible etiology and clinical
      presentation of similar cases. Case 1 is an 18-year-old female with cleft lip and
      palate, syndactyly, and bilateral corneal pannus superiorly and inferiorly. She
      was initially diagnosed and treated as herpes simplex virus keratitis. Case 2 is
      a 3-year-old female born with cleft lip and palate, absent radial digits in both
      hands, and bilateral lacrimal stenosis. She developed progressive stromal
      scarring and neovascularization in both eyes. Her cornea perforated after
      developing infectious ulceration. Case 3 is a 49-year-old male with cleft palate,
      claw-hand deformities, absent meibomian glands and lacrimal duct, right
      ankyloblepharon, and a superior wedge-shaped opacity in the left cornea. The
      clinical findings demonstrated the different spectrum of keratopathy seen in
      patients with EEC. All patients were treated medically and without any surgical
      intervention. Limbal stem cell deficiency (LSCD) is presumed to be the cause in
      all three cases. Corneal changes in EEC can have variable presentation. LSCD
      seems to be the etiology of such keratopathy. Recurrent infection from lacrimal
      drainage obstruction and tear film instability are other risk factors for disease
      severity and progression.

PMID- 22618130
TI  - Spectral-domain optical coherence tomography of astrocytic hamartomas in tuberous
      sclerosis.
AB  - Retinal astrocytic hamartomas are benign tumors of the retinal nerve fiber layer
      (NFL) that may be found in association with tuberous sclerosis (TS). We describe
      the spectral-domain optical coherence tomography (SD-OCT) features of type 1
      astrocytic hamartomas in a child with TS that may aid in the diagnosis and follow
      up of these lesions. Gradual, dome-shaped hyper-reflective elevations of the
      retinal NFL were seen on SD-OCT with subtle shadowing of the underlying tissues.
      In addition, the vitreous cortex showed focal adhesions to the surface of the
      tumor.

PMID- 22618151
TI  - Exploring the trifluoromenadione core as a template to design antimalarial redox
      active agents interacting with glutathione reductase.
AB  - Menadione is the 2-methyl-1,4-naphthoquinone core used to design potent
      antimalarial redox-cyclers to affect the redox equilibrium of Plasmodium-infected
      red blood cells. Exploring the reactivity of fluoromethyl-1,4-naphthoquinones, in
      particular trifluoromenadione, under quasi-physiological conditions in NADPH
      dependent glutathione reductase reactions, is discussed in terms of chemical
      synthesis, electrochemistry, enzyme kinetics, and antimalarial activities.
      Multitarget-directed drug discovery is an emerging approach to the design of new
      antimalarial drugs. Combining in one single 1,4-naphthoquinone molecule, the
      trifluoromenadione core with the alkyl chain at C-3 of the known antimalarial
      drug atovaquone, revealed a mechanism for CF(3) as a leaving group. The resulting
      trifluoromethyl derivative 5 showed a potent antimalarial activity per se against
      malarial parasites in culture.

PMID- 22618152
TI  - The relationship between intracranial arterial stenosis and glomerular filtration
      rate.
AB  - Poor renal function is associated with cardiovascular complications attributable
      to large-vessel diseases such as arterial calcification, heart failure,
      myocardial infarction, and cardiac mortality. The aim of this study was to
      evaluate the association between renal function and intracranial arterial
      stenosis (IAS). We analyzed the records of 283 stroke-free Korean adults (>=45
      years of age) who underwent brain 3D time-of-flight magnetic resonance
      angiography as part of their voluntary health check. The presence of stenosis in
      the basilar artery and in the horizontal portion of the middle cerebral artery
      was defined as narrowing of the luminal diameter by 25% or more or occlusion on
      brain magnetic resonance angiography. We estimated the glomerular filtration rate
      using the Modification of Diet in Renal Disease equation. The subjects were 133
      men and 150 women (mean age of 56 +/- 7 years). One hundred sixty-six subjects
      (59 %) had IAS. The serum creatinine concentration in the highest quartile
      compared with the lowest quartile was associated with increased prevalence of
      IAS; the eGFR in the upper two quartiles compared with the lowest quartile were
      associated with decreased prevalence of IAS. The prevalence of subjects with a
      high eGFR decreased significantly with the severity of IAS. In conclusion, poor
      renal function is associated with the presence and the degree of IAS in stroke
      free Korean adults.

PMID- 22618153
TI  - How to prevent bleeding events in on- and off-pump coronary artery bypass
      patients exposed to clopidogrel preoperatively.

PMID- 22618154
TI  - Hydrothermal synthesis, crystal structure and properties of Ni(II)-4f complexes
      based on 1H-benzimidazole-5,6-dicarboxylic acid.
AB  - Nine novel heterometallic coordination polymers
      [Ln(2)Ni(Hbidc)(2)(SO(4))(2)(H(2)O)(8)](n) (Ln = Pr (1), Sm (2), Eu (3), Gd (4),
      Tb (5), Dy (6), Ho (7), Er (8), Yb (9), H(3)bidc = 1H-benzimidazole-5,6
      dicarboxylic acid) have been synthesized under hydrothermal conditions and
      characterized by elemental analysis, FT-IR, TG analysis and single crystal X-ray
      diffraction. X-ray analysis revealed that all complexes present almost identical
      three-dimensional (3D) structures with PtS-type topology. Complexes 1-7 are all
      isomorphous, and the structure variation of polymers 8 and 9 is induced by the
      lanthanide contraction effect. In additional, the luminescence properties of
      complexes 2, 3 and 5-7, and the magnetic properties of complexes 4 and 6-8 were
      investigated.

PMID- 22618155
TI  - Nonlinear stress analysis of the supraspinatus tendon using three-dimensional
      finite element analysis.
AB  - PURPOSE: No studies have used stress analysis with finite element analysis (FEA)
      to determine the causes of and mechanisms underlying rotator cuff tears.
      Therefore, we performed a biomechanical evaluation of the changes in stress
      distribution on the rotator cuff using three-dimensional (3-D) FEA. METHODS: The
      3-D FEA model of shoulder joint allowed for abduction angles of 0 degrees , 45
      degrees  and 90 degrees  from the plane of the scapula and included the
      anatomical insertion points of the three major rotator cuff tendons and the
      middle fibres of the deltoid muscle. Stress distribution of the supraspinatus
      tendon on 3-D FEA was validated by a comparison with cadaveric and two
      dimensional finite element model. RESULTS: The principal stress peaked in the
      region approximately 1 cm proximal to the insertion of the supraspinatus tendon.
      Furthermore, the stress on the joint side increased at the anterior edge of the
      supraspinatus tendon at abduction angles of 45 degrees  and 90 degrees .
      CONCLUSION: There are differences in stress changes between the joint side and
      bursal side of the supraspinatus tendon within the angles of abduction. The
      maximal tensile stress was observed on the articular side of the anterior edge of
      the supraspinatus tendon at 90 degrees  abduction. Our results indicate that the
      difference in tensile stress between the two layers results in delamination and
      causes partial-thickness tears. LEVEL OF EVIDENCE: Decision analysis, Level II.

PMID- 22618156
TI  - The influence of red laser irradiation timeline on burn healing in rats.
AB  - Low-level laser therapy (LLLT) promotes biomodulation of wound healing and
      literature reports that light delivery during the inflammation could play a
      different role compared with latter phases of the healing process. The objective
      of this study was to investigate whether single dose of a red laser (lambda = 660
      nm) is different from fractionated delivery protocol in full thickness burns. Two
      lesions were inflicted on the back of 36 rats. In the fractionated dose group
      (FG), the lesions were irradiated with 1 J/cm2 on days 1, 3, 8, and 10 post
      wounding. In the single dose group (SG), the lesions were irradiated with 4 J/cm2
      on day 1, immediately after injury. Control lesions (CG) received no light and
      were left to heal spontaneously. Blood flow was measured on days 1, 3, 8, 10, 15,
      and 21 using laser Doppler flowmetry. Animals were killed on days 3, 8, 10, 15,
      and 21. Skin specimens were obtained and routinely processed for hematoxylin and
      eosin. The specimens were evaluated according to differential leukocyte counting
      and angiogenesis. Statistical analysis was performed, and significance was
      accepted at p < 0.05. Irradiated groups showed a peak of new vessels on day 15
      while, for CG, the peak was on day 21. On day 21, FG exhibited a significantly
      greater number of cumulative neutrophils while SG showed a higher number of
      mononuclear cells. Our results confirm that both protocols used accelerate
      angiogenesis and stimulate leukocyte chemotaxis on burn treatment. In addition,
      this work suggests that a single-dose LLLT accelerates the inflammatory phase of
      skin repair.

PMID- 22618157
TI  - A new modality for fractional CO2 laser resurfacing for acne scars in Asians.
AB  - Since fractional photothermolysis was first introduced in 2004, it has become a
      very popular procedure, especially with more and more ablative fractional laser
      systems and treatments. Fractional ablative laser has been shown to be very
      effective; however, it does not reach the efficacy of conventional ablative laser
      treatments in most instances. In an attempt order to make the fractional CO2
      laser treatment more efficacious and safe, we combined both the conventional CO2
      laser and the fractional CO2 laser to treat acne scars. We report our experience
      with this new modality. A total of 44 Chinese patients with facial acne scars and
      skin type IV were included in this study. Each patient received a minimum of two
      treatment sessions. For each laser session, both the conventional CO2 laser
      treatment and the DeepFX laser treatment were focused on treating the scar areas
      only. Following this technique, the more superficialf ActiveFX fractional CO2
      laser was performed to the entire face. The efficacy of the procedure was
      evaluated 3 months after the final laser treatment. The improvement in acne scars
      and the overall skin texture change were assessed by photographic evaluation
      using the following scales: <=25 % (mild), 26-50 % (moderate), 51-75 % (marked),
      and >75 % (excellent). Side effects from this therapy were mild to moderate. Two
      cases of HSV outbreak were noted; they were treated and resolved without adverse
      sequelae. Post-laser erythema was resolved within 1 month in one half of the
      patients. Prolonged erythema (<=3 months) was noted in 12(27 %) cases. Temporary
      post-inflammatory hyperpigmentation (PIH; <=1 month) was seen in approximately 50
      % of the patients. PIH (<=3 months) was noted in four cases (9 %). Sixty-four
      percent of the patients (28/44) had an improvement of between 51 and 75 % after
      more than two sessions of the combination of laser treatments. The average
      overall improvement was 52.50 % (+/-12.25 %). Three patients achieved improvement
      of >75 %. This new modality of ablative conventional CO2 laser therapy with
      fractional CO2 laser resurfacing was shown to be safe and efficacious in the
      treatment of acne scars in Asian patients. It did not increase the risk of PIH
      compared to other reports of laser therapy and PIH. It is the hope that future
      study with combination therapy will further enhance the clinical results and thus
      lessen potential adverse events.

PMID- 22618158
TI  - Quantitative measurement of optical attenuation coefficients of cell lines CNE1,
      CNE2, and NP69 using optical coherence tomography.
AB  - The radiotherapy-related types of nasopharyngeal carcinoma (NPC) have been
      established, which give the most effective treatment for NPC patients using the
      individual therapy. To diagnose the types of NPC, we assess the general NPC cell
      lines CNE1, CNE2 and normal nasopharyngeal cell line NP69 using optical coherence
      tomography (OCT) in two steps: firstly, the OCT images of the three different
      types of cell pellets are captured. Secondly, by fitting Beer's law to the
      averaged A-scans in these OCT datasets, the attenuation coefficients (MU t ) of
      the cells can be extracted. The median attenuation coefficients (interquartile
      range) of CNE1, CNE2, and NP69 are 5.58 mm(-1) (IQR 5.55 to 5.65 mm(-1)), 5.91
      mm(-1) (IQR 5.82 to 5.88 mm(-1)), and 8.96 mm(-1) (IQR 8.80 to 9.47 mm(-1)),
      respectively. The distinguishable quantitative OCT analysis (by MU t ) shows that
      the types of NPC could potentially be differentiated in real time and
      noninvasive.

PMID- 22618159
TI  - [Skin antiseptics in plastic surgery].
AB  - BACKGROUND: Wound healing is a complex proces, which is influenced by multiple
      factors. Bacterial contamination and infection are frequent and severe
      complications. The treatment of such infected wounds is a major challenge to the
      plastic surgeon. The topical application of wound antiseptics is widely used as a
      therapeutic approach in the treatment of these wounds. This review provides an
      overview about their clinical application, their cytotoxic and antibacterial
      properties as well as interactions with commonly used wound dressings. MATERIAL
      AND METHODS: This article reviews current literature dealing with local
      antiseptics, antibacterial activity, cytotoxicity and compatibility with wound
      dressings. RESULTS: Topical antiseptics are used on a daily basis in order to
      reduce bacterial wound contamination. However, few data exist concerning their
      antimicrobial activity, especially in relation to their cytotoxicity.
      Furthermore, their compatibility with wound dressings is barely investigated.
      Recent studies show significant toxic effects on cells and an incompatibility
      with certain wound dressings for some of these antiseptics. DISCUSSION:
      Antiseptics are broadly used in healthcare to reduce, inactivate or eliminate
      bacterial pathogens. Recent studies show that many daily used antiseptics possess
      relevant cytotoxic properties as well as cross reactions with wound dressings.
      Additional studies are therefore needed to further investigate and characterize
      the properties of wound antiseptics in order to identify the optimal therapeutic
      agents for the treatment of infected wounds.

PMID- 22618160
TI  - [The medical treatment of Kim Phuc at the BG Unfallklinik Ludwigshafen].
AB  - The Vietnam War was a military conflict in Vietnam during the Cold War that
      followed the First Indochina War. This war was fought between North Vietnam,
      supported by its communist allies, and the government of South Vietnam, supported
      by the USA and other anti-communist countries. Kim Phuc is the child depicted in
      the Pulitzer Prize winning photograph taken on June 8, 1972 by AP photographer
      Nick Ut. The iconic photo shows her at about nine years of age running naked on a
      road amid the chaos after being severely burned by a napalm attack. After 14
      months of hospital stay and 17 surgical procedures Kim Phuc was able to return
      home. Since then, she was used as a propaganda symbol by the communist government
      of Vietnam. To continue her studies, Kim was granted permission to move to Cuba
      where she met her future husband. However, the sequelae of her burn wounds
      affected her everyday life enormously. In 1984, with the support of the
      international aid organization "terre des hommes" and the German magazine
      "STERN", Kim Phuc got the opportunity to meet and get treated by Professor
      Zellner. Professor Peter Rudolph Zellner was the first chief of the Department of
      Hand, Plastic and Reconstructive Surgery, Burn Center, BG Trauma Center
      Ludwigshafen, and one of the founder members of the German Society of Plastic
      Surgeons. The reconstructive surgeries provide Kim Phuc an almost normal life.
      Later on, she was involved in international aid organizations; she was named a
      UNESCO Goodwill Ambassador and she was awarded several honorary Doctorates of
      Law. Kim Phuc became a Canadian citizen. Today, she lives with her husband and
      two children in Ontario, Canada.

PMID- 22618161
TI  - Compassion, ethics, and neuroscience: neuroethics through Buddhist eyes.
AB  - As scientists advance knowledge of the brain and develop technologies to measure,
      evaluate, and manipulate brain function, numerous questions arise for religious
      adherents. If neuroscientists can conclusively establish that there is a
      functional network between neural impulses and an individual's capacity for moral
      evaluation of situations, this will naturally lead to questions about the
      relationship between such a network and constructions of moral value and ethical
      human behavior. For example, if cognitive neuroscience can show that there is a
      neurophysiological basis for the moral appraisal of situations, it may be argued
      that the world's religions, which have traditionally been the keepers and
      purveyors of ethical values, are rendered either spurious or irrelevant. The
      questions point up broader dilemmas in the interface between science and
      religion, and raise concerns about the ethics of neurological research and
      experimentation. Since human beings will still arbitrate what is "moral" or
      "ethical," how can religious perspectives enrich the dialogue on neuroethical
      issues and how can neuroscience enrich dialogue on religion? Buddhist views on
      the nature of consciousness and methods of practice, especially meditation
      practice, may contribute to discussions on neuroscience and theories about the
      interrelationship between consciousness and ethical awareness by exploring the
      role that karma, intentionality, and compassion play in Buddhist understandings
      of the interrelationship between consciousness and ethics.

PMID- 22618162
TI  - An analysis of student privacy rights in the use of plagiarism detection systems.
AB  - Plagiarism detection services are a powerful tool to help encourage academic
      integrity. Adoption of these services has proven to be controversial due to
      ethical concerns about students' rights. Central to these concerns is the fact
      that most such systems make permanent archives of student work to be re-used in
      plagiarism detection. This computerization and automation of plagiarism detection
      is changing the relationships of trust and responsibility between students,
      educators, educational institutions, and private corporations. Educators must
      respect student privacy rights when implementing such systems. Student work is
      personal information, not the property of the educator or institution. The
      student has the right to be fully informed about how plagiarism detection works,
      and the fact that their work will be permanently archived as a result.
      Furthermore, plagiarism detection should not be used if the permanent archiving
      of a student's work may expose him or her to future harm. 

PMID- 22618163
TI  - Gustatory, trigeminal, and olfactory aspects of nicotine intake in three mouse
      strains.
AB  - Studies of nicotine consumption in rodents often intend to investigate nicotine's
      post-absorptive effects, yet little is known about the pre-absorptive sensory
      experience of nicotine drinking, including gustatory, trigeminal, and olfactory
      influences. We conditioned taste aversion (CTA) to nicotine in males of 3 inbred
      mouse strains: C57BL/6J, DBA/2J, and 129X1/SvJ by repeatedly pairing 150 MUg/ml
      nicotine drinking with lithium chloride injections. Generalization to a variety
      of bitter, sour, sweet, salty, and irritant solutions and to nicotine odor was
      then examined. Nicotine CTA generalized to the bitter stimulus quinine
      hydrochloride and the chemosensory irritant spilanthol in all strains. It also
      showed strain specificity, generalizing to hydrogen peroxide (an activator of
      TRPA1) in C57BL/6J mice and to the olfactory cue of nicotine in DBA/2J mice.
      These behavioral assays demonstrate that the sensory properties of nicotine are
      complex and include multiple gustatory, irritant, and olfactory components. How
      these qualities combine at the level of perception remains to be assessed, but
      sensory factors clearly exert an important influence on nicotine ingestion and
      their contribution to net intake of nicotine should not be neglected in animal or
      human studies.

PMID- 22618190
TI  - Tifton hay, soybean hulls, and whole cottonseed as fiber source in spineless
      cactus diets for sheep.
AB  - The objective of this paper was to evaluate the effect of three different sources
      of fiber (tifton hay, soybean hulls, and whole cottonseed) in spineless cactus
      diets for sheep in the semiarid region of northeastern Brazil. Twenty-one sheep
      in finishing phase with indeterminate breed, non-castrated, and with initial
      weight of 18.90 +/- 1.07 kg were randomly distributed to individual stalls where
      they were confined for the duration of the experiment. The intakes of dry and
      organic matter, total carbohydrates, and total digestive nutrients were not
      influenced (P > 0.10) by the different fiber sources (1.10, 0.97, 0.73, and 0.80
      kg/day, respectively). However, sheep which received the whole cottonseed diet
      were characterized by a lower (P < 0.10) intake of crude protein and neutral
      detergent fiber and greater (P < 0.10) intake of ether extract (0.11, 0.29, and
      0.048 kg/day, respectively). The different sources of fiber resulted in similar
      times spent feeding (P > 0.10), although the rumination time was greater for
      tifton hay (P < 0.10) (429.05 min/day). The digestibility coefficient of dry and
      organic matter differed between the treatments (P < 0.10), with the soybean hull
      diet showing a higher level of digestion (83.23 and 86.72 %, respectively). The
      whole cottonseed diet gave the smallest digestibility coefficient of crude
      protein (68.95 %) and greatest for ether extract (85.94 %). The daily weight gain
      of animals fed on whole cottonseed was significantly lower (P < 0.10). On the
      basis of these findings, we recommend the use of tifton hay or soybean hulls as
      important additional source of fiber in forage spineless cactus diets for sheep
      in finishing phase.

PMID- 22618191
TI  - Phylogenetic analysis of Newcastle disease viruses isolated from asymptomatic
      guinea fowls (Numida meleagris) and Muscovy ducks (Cariana moscata) in Nigeria.
AB  - Four Newcastle disease virus isolates were recovered from asymptomatic guinea
      fowl (Numida meleagris galeata) and Muscovy ducks (Cariana moscata). For the
      purpose of molecular identification and phylogeny, phylogenetic characterization
      was performed to identify the pathotypes. All four viruses had a cleavage motif
      (112)RRQKRF(117) which is characteristic of virulent strains. The isolates
      grouped with viruses previously reported as sub-lineage 5 g from chickens in
      Nigeria. This study report for the first time the identification of the virulent
      sub-lineage 5 g Newcastle disease virus from apparently healthy guinea fowl and
      domestic ducks in Nigeria, and since infections were sub-clinical, it suggest
      that these species could play a role in the spread and transmission of virulent
      Newcastle disease virus that can infect other poultry. The isolation and
      identification of virulent Newcastle disease virus in these unusual hosts and the
      high sequence similarity (99.3-100 %) between viruses in this study with strains
      reported for Niger and Cameroun gives insights into the ecology of virulent
      Newcastle disease viruses and suggests some cross-border movement and trade in
      live poultry.

PMID- 22618192
TI  - Improving village poultry's survival rate through community-based poultry health
      management: evidence from Benin.
AB  - Community-based poultry health management (CBM) is a strategy for village poultry
      improvement based on the installment of "poultry interest groups" in experimental
      villages. These groups serve as a channel for the dissemination of village
      poultry improvement technologies. The use of CBM is due to the fact that village
      poultry farming is practiced in a total or partial scavenging system which gives
      the impression that all the birds in the village belong to the same flock.
      Accordingly, actions that target all farmers of the same village may have a
      larger impact on the village poultry's survival rate than actions that target
      individual producers. The objective of this study is to assess the impact of CBM
      on the survival rate of village poultry. Based on data collected on 353 poultry
      keepers, the study shows that CBM significantly improves the survival rate of
      village poultry. The adoption of technologies--poultry vaccination, construction
      of henhouses, and improved feed--disseminated through the CBM also significantly
      improves the survival rate. The access to markets for inputs and veterinary
      services is also important in improving the survival rate of poultry. Finally,
      the study suggests that governments and development agencies can improve village
      poultry survival rates by investing in the dissemination of information regarding
      best husbandry management practices through approaches that rely on the community
      such as CBM because CBM groups serve as channels for the dissemination of village
      poultry improvement technologies.

PMID- 22618194
TI  - Characteristics of chromosomal abnormalities diagnosed after spontaneous
      abortions in an infertile population.
AB  - PURPOSE: To estimate the prevalence of chromosomally abnormal related
      miscarriages in an infertile population. METHODS: Retrospective analysis of
      cytogenetics obtained by chorionic villi harvesting of the first miscarriage
      cycle of infertile patients at our center from 2001-2010 were reviewed. Abnormal
      results were characterized as trisomy, monosomy X, structural, or other. Age, #
      of eggs, #2PN, # embryos transferred, day of transfer, and performance of
      intracytoplasmic sperm injection (ICSI) were recorded. RESULTS: In a study
      population of 299 patients with a mean age of 38.0 +/- 4.5 y, 276(92 %) patients
      had some form of assisted reproductive technologies (ART), and 244(82 %) had IVF.
      Of all results, 71.6 % had an abnormal karyotype. Patients with abnormal
      cytogenetics were older (38.6 +/- 4.1 vs. 36.3 +/- 4.9, p < 0.001), and more
      likely to have a day 3 transfer (age < 38 ( 20.7 %) vs. age 38 (46.3 %), p =
      <0.001) with more embryos transferred (3.0 +/- 1.2, vs. 2.3 +/- 0.9, p < 0.001).
      The performance of ICSI did not affect the rate of cytogenetically abnormal
      products of conception (ICSI 68.3 % vs. no ICSI 70.7 %). In comparing patients,
      monosomy X was more common in <38 y. Rates of trisomy, although not statistically
      significant, were higher in older patients. CONCLUSIONS: The classic associations
      between advancing age and chromosomal abnormalities, and younger age and monosomy
      X, are affirmed in our infertile population. There was no increase in chromosomal
      abnormalities in cycles where ICSI was performed. Older patients are more likely
      to have day 3 transfers and more embryos transferred. Our chromosomal abnormality
      rates are higher than classic estimates but comparable to recent studies. The
      limitation of this study was a lack in uniformity among practitioners in
      recommending all patients have a Dilation and Curettage (D&C) at time of
      diagnosis. Such information may serve to improve the counseling of patients after
      miscarriage.

PMID- 22618193
TI  - Abnormal DNA methylation in oocytes could be associated with a decrease in
      reproductive potential in old mice.
AB  - PURPOSE: This study was designed to evaluate DNA methylation and the expression
      of DNA methyltransferases (Dnmt1, Dnmt3a, Dnmt3b and Dnmt3L) in metaphaseII (MII)
      oocytes and the DNA methylation of pre-implantation embryos during mouse aging to
      address whether such aging-related changes are associated with decreased
      reproductive potential in aged mice. METHODS: Oocytes (MII) from 6 to 8 weeks old
      female mice are referred to as the 'young group'; oocytes from the same group
      that were maintained until 35-40 weeks old are referred to as the 'old group.'
      The oocytes were fertilized both in vitro and in vivo to obtain embryos. The DNA
      methylation levels in the oocytes (MII) and pre-implantation embryos were
      assessed using fluorescence staining. The expression levels of the Dnmt genes in
      the oocytes (MII) were assessed using Western blotting. RESULTS: The DNA
      methylation levels in the oocytes and pre-implantation embryos (in vivo and in
      vitro) decreased significantly during the aging of the mice. The expression
      levels of all of the examined Dnmt proteins in the old group were lower than
      young group. Both the cleavage and blastocyst rate were significantly lower in
      the oocytes of the older mice (69.9 % vs. 80.9 %, P < 0.05; 33.9 % vs. 56.4 %, P
      < 0.05). The pregnancy rate of the old mice was lower than that of the young mice
      (46.7 % vs. 100 %, P < 0.05). The stillbirth and fetal malformation rate was
      significantly higher in the old group than in the young group (17.2 % vs. 2.9 %,
      P < 0.05). CONCLUSIONS: The decreased expression of Dnmt1, Dnmt3a, Dnmt3b and
      Dnmt3L in oocytes (MII) and the change of genome-wide DNA methylation in oocytes
      and pre-implantation embryos due to aging may be related to lower reproductive
      potential in old female mice.

PMID- 22618195
TI  - Supernumerary blastocyst cryopreservation: a key prognostic indicator for
      patients opting for an elective single blastocyst transfer (eSBT).
AB  - OBJECTIVE: To determine if patients, less than 40 years of age with or without
      day 5 cryopreservation (d5 cryo), compromise their pregnancy rate (PR) by
      choosing an eSBT. DESIGN: Retrospective analysis SETTING: University IVF center
      PATIENTS: 2,203 non-donor fresh IVF cycles in women <40 years of age from January
      2004 to January 2010. INTERVENTIONS: None MAIN OUTCOME MEASURE(S): Eggs
      retrieved, Embryos cryopreserved, Implantation Rates, Clinical Pregnancy Rates,
      Live Birth Rates, Spontaneous Abortion Rates RESULTS: Pregnancy outcomes in women
      <40 years with or without d5 cryo were compared according to whether patients
      underwent an eSBT versus a 2BT in non-donor fresh IVF cycles. Overall, eSBT was
      associated with elimination of twinning while maintaining a high clinical
      pregnancy rate in both groups with d5 cryo (75 % eSBT versus 72 % 2BT) and groups
      without d5 cryo (48 % eSBT versus 56 % 2BT). CONCLUSIONS: In this study, patients
      <40 years of age have eliminated twinning by electively choosing to transfer a
      single blastocyst without compromising their PR if embryos are available for d5
      cryo, and suffer only a non-statistically significant drop in their PR if there
      are no embryos available for d5 cryo in exchange for the benefit of eliminating
      the obstetrical risk of twinning.

PMID- 22618196
TI  - Metal/metal sulfide functionalized single-walled carbon nanotubes: FTO-free
      counter electrodes for dye sensitized solar cells.
AB  - The use of single-walled carbon nanotubes (CNT) thin films to replace
      conventional fluorine-doped tin oxide (FTO) and both FTO and platinum (Pt) as the
      counter electrode in dye sensitized solar cells (DSSC) requires surface
      modification due to high sheet resistance and charge transfer resistance. In this
      paper, we report a simple, solution-based method of preparing FTO-free counter
      electrodes based on metal (Pt) or metal sulfide (Co(8.4)S(8), Ni(3)S(2))
      nanoparticles/CNT composite films to improve device performance. Based on
      electrochemical studies, the relative catalytic activity of the composite films
      was Pt > Co(8.4)S(8) > Ni(3)S(2). We achieved a maximum efficiency of 3.76% for
      the device with an FTO-free counter electrode (Pt/CNT). The device with an FTO-
      and Pt-free (CoS/CNT) counter electrode gives 3.13% efficiency.

PMID- 22618197
TI  - Folding super-sized DNA origami with scaffold strands from long-range PCR.
AB  - A 26 kilobase single strand DNA fragment was obtained from long-range PCR
      amplification and subsequent enzymatic digestion, which we folded into a super
      sized DNA origami nanostructure by using ~800 staple strands.

PMID- 22618198
TI  - Highly efficient intramolecular Cannizzaro reaction between 1,3-distal formyl
      groups at the upper rim of a cone-calix[4]arene.
AB  - The 1,3-distal cone-calix[4]arene dialdehyde 1 undergoes Cannizzaro
      disproportionation in the presence of strong base, but its 1,2-vicinal
      regioisomer 3 and the analogous monoaldehyde 2 are unreactive under the same
      conditions. The high intramolecular reactivity of the 1,3-distal regioisomer 1 is
      measured and discussed in terms of Effective Molarity (EM).

PMID- 22618199
TI  - Effect of TiO2 support on the structural and electronic properties of PdmAgn
      clusters: a first-principles study.
AB  - First-principles density functional theory studies have been carried out to
      investigate the effects of perfect and defective anatase TiO2 supports on the
      structural stabilities and electronic properties of PdmAgn(m + n = 2-5)
      bimetallic clusters. Our results showed that the structures of supported Pd-Ag
      bimetallic clusters are distorted compared to their structures in the gas phase,
      which is caused by the balance of the cluster inner-interaction and the metal
      support interfacial interaction. In particular, Pd1Ag3 and Pd1Ag4 clusters prefer
      to form three-dimensional structures on both perfect and defective anatase TiO2
      support while their most stable structures in the gas phase are planar. In the
      most stable structures of supported PdmAgn bimetallic clusters, Pd atoms always
      occupy the most active sites of TiO2(101) surface, which induced Pd enriched at
      the interface of TiO2 support and Ag atoms exposed at the surface of the
      bimetallic cluster. As Ag% increases, the perfect TiO2 support gets more
      electrons from the Pd-Ag bimetallic cluster, which reduced the stability of the
      supported Pd-Ag cluster. The Mulliken population and electron density difference
      analysis demonstrated that the co-deposition of Ag induced the charge of adsorbed
      Pd on the perfect TiO2 support from positive to negative as a result of charge
      transfer from the half-filled s-orbital of Ag(5s(1)) to the d-orbit of Pd, and
      the negative charges of Pd on the defective TiO2 support were also increased by
      Pd-Ag charge polarization. Therefore, the selectivity of acetylene hydrogenation
      is enhanced by anatase-TiO2 supported Pd-Ag bimetallic catalyst as it serves as
      an electron donor. 

PMID- 22618200
TI  - Omega-6 docosapentaenoic acid-derived resolvins and 17-hydroxydocosahexaenoic
      acid modulate macrophage function and alleviate experimental colitis.
AB  - OBJECTIVE: Enzymatically oxygenated lipid products derived from omega-3 and omega
      6 fatty acids play an important role in inflammation dampening. This study
      examined the anti-inflammatory effects of n-6 docosapentaenoic acid-derived (17S)
      hydroxy-docosapentaenoic acid (17-HDPAn-6) and (10,17S)-dihydroxy
      docosapentaenoic acid (10,17-HDPAn-6) as well as n-3 docosahexaenoic acid-derived
      17(R/S)-hydroxy-docosahexaenoic acid (17-HDHA). MATERIALS AND METHODS: The
      effects of 17-HDPAn-6, 10,17-HDPAn-6 or 17-HDHA on activity and M1/M2
      polarization of murine macrophage cell line RAW 264.7 were examined by
      phagocytosis assay and real-time PCR. To assess anti-inflammatory effects in
      vivo, dextran sodium sulfate (DSS) colitis was induced in mice treated with 17
      HDPAn-6, 10,17-HDPAn-6, 17-HDHA or NaCl. RESULTS: Our results show that 17-HDPAn
      6, 10,17-HDPAn-6 and 17-HDHA increase phagocytosis in macrophages in vitro and
      promote polarization towards the anti-inflammatory M2 phenotype with decreased
      gene expression of TNF-alpha and inducible Nitric oxide synthase and increased
      expression of the chemokine IL-1 receptor antagonist and the Scavenger receptor
      Type A. Intraperitoneal treatment with 17-HDPAn-6, 10,17-HDPAn-6, or 17-HDHA
      alleviated DSS-colitis and significantly improved body weight loss, colon
      epithelial damage, and macrophage infiltration. CONCLUSION: These results suggest
      that DPAn-6-derived 17-HDPAn-6 and 10,17-HDPAn-6 as well as the DHA-derived 17
      HDHA have inflammation-dampening and resolution-promoting effects that could be
      used to treat inflammatory conditions such as inflammatory bowel disease.

PMID- 22618203
TI  - Functionalisation of lanthanide complexes via microwave-enhanced Cu(I)-catalysed
      azide-alkyne cycloaddition.
AB  - Cu(I)-catalysed azide-alkyne cycloaddition reactions were used to functionalise
      lanthanide(III)-complexes (Ln; La, Eu and Tb) incorporating alkyne or azide
      reactive groups. Microwave irradiation significantly accelerated the reactions,
      enabling full conversion to the triazole products in some cases in 5 min. Alkyl
      and aryl azides and alkyl and aryl alkynes could all serve as coupling partners.
      These reaction conditions proved efficient for cyclen-tricarboxylates and
      previously unreactive cyclen-tris-primary amide chelates. The synthesis of
      heterobimetallic (Eu/Tb, EuTb17 and Eu/La, EuLa17) and heterotrimetallic
      (Eu/La/Eu) complexes was achieved in up to 60% isolated yield starting from
      coumarin 2-appended alkynyl complexes Tb16 or La16 and an azido-Eu complex Eu4,
      and bis-alkynyl La-complex La5 and Eu4, respectively. EuTb17 displayed dual
      Eu(III) and Tb(III)-emission upon antenna-centred excitation.

PMID- 22618201
TI  - NF-kappaBeta inhibition is ineffective in blocking cytokine-induced IL-8
      production but P38 and STAT1 inhibitors are effective.
AB  - OBJECTIVE: In vitro but not in vivo evidence indicates that blockade of NF-kappaB
      is effective in reducing inflammation and production of IL-8. We hypothesized
      that the failure of in vitro experiments to predict in vivo outcome was due to
      the use of short time periods of observation and the use of single cytokines to
      stimulate NF-kappaB. METHODS: HEK cells with a NF-kappaB reporter gene or CaCo-2
      cells were stimulated with CM (IL-1-beta; TNF-alpha, and IFN-gamma) or individual
      cytokines in the presence and absence of NF-kappaB inhibitors, a STAT1 inhibitor,
      and/or a p38 MAPK inhibitor for periods up to 24 h. NF-kappaB activation, IL-8
      production, and nitric oxide production were measured. RESULTS: CM-induced IL-8
      production in HEK cells was additive to synergistic. CM enhanced production of IL
      8 at 24 h but not 4 h was independent of NF-kappaB. The p38 inhibitor SB203580
      and the STAT1 inhibitor EGCG blocked CM-induced IL-8 production at both early and
      late time periods. The NF-kappaB inhibitors PDTC and BAY11-7082 were found to
      increase CM-stimulated IL-8 production in Caco-2 cells at 24 h. CONCLUSIONS: Our
      data suggest an effective strategy to reduce IL-8 production is to block p38 or
      STAT1 rather than NF-kappaB.

PMID- 22618202
TI  - Metabolomic study of serum from rabbits with acute acalculous cholecystitis.
AB  - OBJECTIVES: (1)H-NMR is a powerful approach of metabolomics. This study aimed to
      apply it to detect the serum metabolites in rabbits with acute acalculous
      cholecystitis (AAC), and to analyze their potential roles in AAC. METHODS:
      Fourteen rabbits were randomly divided into two groups, the AAC group and the CON
      group. In the AAC rabbit model, Escherichia coli solution was injected into the
      gallbladder, while same volume of saline, instead of E. coli solution, was
      injected into the gallbladder of the CON rabbit. General morphological, light
      microscopic and transmission electron microscopic observations were used to
      evaluate the model. Metabolic profiles of serum from rabbits with AAC were
      investigated through (1)H-NMR spectroscopy coupled with multivariate statistical
      analysis, such as principal components analysis and orthogonal partial least
      squares discriminant analysis. RESULTS: The pathohistology of gallbladders showed
      a significant difference between the two groups, proving the successful induction
      of inflammation in the gallbladders of the AAC group. The serum concentration of
      lipids (LDL and VLDL) increased during AAC, while the concentrations of
      phospholipids, lactic acid, 3-hydroxybutyric acid, lysine, citric acid,
      asparagine, histidine, glucose and some other small molecular metabolites
      decreased. CONCLUSION: The profiling of serum metabolites in rabbits with acute
      acalculous cholecystitis changed significantly. These changes referred to the
      metabolic disturbance of carbohydrate, amino acids and lipids, inhibition of
      immunological functions and inflammation reaction.

PMID- 22618204
TI  - Prevalence study of stress urinary incontinence in women who perform high-impact
      exercises.
AB  - INTRODUCTION: Stress urinary incontinence is a frequent complaint in medical
      offices and studies have shown that women who practice high impact sports develop
      its symptoms. OBJECTIVE: To evaluate the prevalence of stress urinary
      incontinence in women who attend gyms and perform high impact exercises and
      correlate it with women who do not attend gyms. METHOD: Prospective comparative
      study in which 488 nulliparous women of normal weight were divided into a Study
      Group, composed of women who attended gyms, and a Comparative Group, composed of
      women who did not attend gyms. Three questionnaires were used for the evaluation
      of stress urinary incontinence and the results of the ICIQ-SF questionnaire were
      used to compare the groups. RESULTS: There was a significant difference between
      groups on the ICIQ-SF. The average in the Study Group was 1.68 (+ 3.46) and in
      the Comparative Group the average was 1.02 (+ 2.69) (p = 0.006). CONCLUSION:
      Women who attend gym and perform high impact exercises have a higher prevalence
      of urinary incontinence symptoms, independent of the exercise modality, than
      women who do not perform any high impact exercise.

PMID- 22618205
TI  - Clinical examination remains more important than anorectal function tests to
      identify treatable conditions in women with constipation.
AB  - INTRODUCTION AND HYPOTHESIS: Many women with chronic constipation are referred
      for anorectal function tests (AFT) when they fail initial conservative treatment
      with lifestyle advice and laxatives. Our goal was to prospectively investigate
      the diagnostic potential of AFT in women with constipation in order to identify
      treatable conditions. METHODS: Between May 2003 and June 2011, all women with
      constipation referred to our tertiary referral center completed a questionnaire
      regarding their perianal complaints and underwent physical examination and were
      evaluated according to our AFT protocol, including anorectal manometry (ARM) and
      anal endosonography. RESULTS: One hundred and thirteen women were referred and
      classified as having idiopathic constipation (n = 100), neurological disorder (n
      = 8), or others (n = 5). Of the 100 women with idiopathic constipation, clinical
      examination identified 25 (25 %) with hypertonia of the pelvic floor (dyssynergic
      pelvic floor) and 15 (15 %) with a rectocele. In 37/100 women also complaining of
      impaired evacuation, the yield of rectocele was 15 (41 %) and of hypertonia 5 (14
      %). Women with hypertonia were younger (40 vs. 51 years; P = 0.002) and had no
      rectoceles identified (P = 0.02), and fewer women could relax during straining on
      ARM (56 % vs. 92 %; P < 0.001) compared with women without pelvic hypertonia.
      Other ARM measurements showed no differences between women with evacuation
      disorders, rectoceles, or hypertonia. Anal endosonography showed no internal
      sphincter hypertrophia. CONCLUSION: Potentially treatable conditions, such as
      rectocele and pelvic floor hypertonia, are found on clinical examination in 40 %
      of women with idiopathic constipation. Impaired evacuation is associated with the
      presence of a rectocele. AFT contributes little and should be reserved for
      selected cases.

PMID- 22618206
TI  - Low back pain does not improve with surgical treatment of pelvic organ prolapse.
AB  - INTRODUCTION AND HYPOTHESIS: Our goal was to determine if there is a correlation
      between low back pain (LBP) and pelvic organ prolapse (POP) by assessing for
      change in LBP after surgical correction of prolapse. METHODS: Patients undergoing
      POP surgery were recruited to participate. They completed the Oswestry Disability
      Index (ODI), a validated back pain questionnaire, at their preoperative and
      postoperative visits at 1, 3, and 6 months. A higher ODI score (0-100) represents
      more severe disability. A 9-point change represents a minimal clinically
      important difference (MCID). The primary outcome was the change in ODI scores
      from preoperative to 3 months postoperative. We analyzed ODI scores with repeated
      measures analysis of variance (ANOVA). Power analysis showed that a sample size
      of 50 was needed for 88 % power to resolve a MCID on ODI. RESULTS: A total of 51
      patients were recruited and 43 (84 %), 34 (67 %), and 36 (71 %) completed the 1-,
      3-, and 6-month follow-up, respectively. The mean ODI scores at the preoperative
      and the 1-, 3-, and 6-month postoperative visits were 15, 19, 9, and 9. The mean
      ODI score from preoperative to 3 months postoperative improved by 5 points
      [confidence interval (CI) -9.2 to -0.5, p = 0.03]. Of the participants 7 (20.6 %,
      CI 11-35 %) experienced a MCID improvement, 24 (70.6 %, CI 56-83 %) reported no
      substantial change, and 3 (8.8 %, CI 3-20 %) experienced a MCID worsening.
      CONCLUSIONS: Our study found a statistically significant but not clinically
      significant improvement of LBP after surgical repair of prolapse.

PMID- 22618207
TI  - Cardinal and deep uterosacral ligament lines of action: MRI based 3D technique
      development and preliminary findings in normal women.
AB  - INTRODUCTION AND HYPOTHESIS: The cardinal ligament (CL) and deep uterosacral
      ligament (US) play a critical role in utero-vaginal support. This study aims to
      quantify their geometrical relationships in living women using a MRI-based 3D
      technique. METHODS: The angles between ligaments, the ligaments length and
      curvature were assessed on 3D models constructed from twenty MRIs of volunteers
      with normal support. How angle variation theoretically affects ligament tension
      was investigated using a simplified biomechanical model. RESULTS: The CLs are
      18.1  degrees  +/- 6.8  degrees (SD) from the cephalic-caudal body axis , and the
      USs are dorsally directed and 92.5  degrees  +/- 13.5 from the body axis. The CLs
      are longer and more curved than US. The theoretical calculated tension on CL is
      52 % larger than that on US. CONCLUSIONS: The CL is relatively parallel to the
      body axis while the US is dorsally directed. The tensions on these ligaments are
      affected by their orientations.

PMID- 22618208
TI  - Clinical evaluation of a wireless intra-vaginal pressure transducer.
AB  - OBJECTIVE: To describe the development, feasibility and validity of a wireless
      intra-vaginal pressure transducer (IVT) which can be used to measure intra
      abdominal pressure in real-world settings. STUDY DESIGN: A feasibility study was
      conducted in sixteen physically active women to determine retention and comfort
      of various IVT prototype designs during activity. A criterion validity study was
      conducted among women undergoing urodynamic testing to determine the accuracy of
      the IVT prototypes when compared to accepted clinical standards. RESULTS: A final
      prototype wireless IVT was developed after four design revisions of the second
      generation model. The feasibility study found that women reported the final
      prototype comfortable to wear and easily retained during physical activity. Intra
      abdominal pressure measurements from the final prototype IVT compared favorably
      to standard urodynamic transducers, thus confirming evidence of its utility.
      CONCLUSION: We have successfully advanced the design of a wireless, intra-vaginal
      pressure transducer which provides accurate measures of intra-abdominal pressure.
      The final wireless IVT is better tolerated by patients and overcomes limitations
      of traditional urodynamic testing while laying the foundations for intra
      abdominal pressure monitoring outside of the clinic environment.

PMID- 22618210
TI  - Impact of a best clinical therapy management on surgery for ulcerative colitis.

PMID- 22618209
TI  - Anatomy and histology of apical support: a literature review concerning cardinal
      and uterosacral ligaments.
AB  - The objective of this work was to collect and summarize relevant literature on
      the anatomy, histology, and imaging of apical support of the upper vagina and the
      uterus provided by the cardinal (CL) and uterosacral (USL) ligaments. A
      literature search in English, French, and German languages was carried out with
      the keywords apical support, cardinal ligament, transverse cervical ligament,
      Mackenrodt ligament, parametrium, paracervix, retinaculum uteri, web, uterosacral
      ligament, and sacrouterine ligament in the PubMed database. Other relevant
      journal and textbook articles were sought by retrieving references cited in
      previous PubMed articles. Fifty references were examined in peer-reviewed
      journals and textbooks. The USL extends from the S2 to the S4 vertebra region to
      the dorsal margin of the uterine cervix and/or to the upper third of the
      posterior vaginal wall. It has a superficial and deep component. Autonomous nerve
      fibers are a major constituent of the deep USL. CL is defined as a perivascular
      sheath with a proximal insertion around the origin of the internal iliac artery
      and a distal insertion on the cervix and/or vagina. It is divided into a cranial
      (vascular) and a caudal (neural) portions. Histologically, it contains mainly
      vessels, with no distinct band of connective tissue. Both the deep USL and the
      caudal CL are closely related to the inferior hypogastric plexus. USL and CL are
      visceral ligaments, with mesentery-like structures containing vessels, nerves,
      connective tissue, and adipose tissue.

PMID- 22618228
TI  - Idiopathic dilated cardiomyopathy: possible triggers and treatment strategies.
AB  - Despite recent advances in the management of patients with heart failure,
      morbidity and mortality rates remain high. Common causes of heart failure are
      ischaemic heart disease, uncontrolled hypertension and valvular disease. However,
      in up to 50 % of the cases its exact cause remains initially unknown; this
      condition is called idiopathic dilated cardiomyopathy (DCM). Improved diagnostic
      methods, most notably the advancements in molecular and immunohistological biopsy
      techniques and genetic research, have endorsed a new era in the diagnosis and
      classification of patients with idiopathic DCM. These insights have led to novel
      aetiology-based treatment strategies and improved outcome. The present article
      will briefly discuss all causes of DCM with a special focus on inflammatory- and
      virus-mediated forms of DCM.

PMID- 22618211
TI  - Facilitated early ileostomy closure after rectal cancer surgery: a case-matched
      study.
AB  - BACKGROUND: The aim of this study was to evaluate the outcomes of an early stoma
      closure protocol facilitated by Seprafilm wrapping of defunctioning ileostomies
      compared with a similar group of patients with conventional stoma formation and
      closure. METHODS: Consecutive patients undergoing defunctioning ileostomy
      following rectal resection with pelvic anastomosis were planned for early closure
      and had their ileostomy wrapped in Seprafilm at the time of formation. Stoma
      closure was performed at 4-6 weeks if water-soluble contrast enema showed no
      evidence of leak, and the patient's physiological parameters had been optimized.
      Patients were matched for age, gender, American Society of Anaesthesiologists
      score, neoadjuvant treatment and procedure, with patients undergoing conventional
      ileostomy formation and closure. Outcomes were compared using the 2-tailed Mann
      Whitney U test and Fisher's exact test. RESULTS: Following resection, twenty-two
      patients (69 %) were suitable for early closure and underwent stoma closure at a
      median of 37 days (range 25-90 days). Seprafilm-wrapped ileostomies were closed
      earlier than the conventional ileostomies (median 55 days (range 25-250 days)
      versus 213 days (range 86-352 days), p < 0.001). There was no difference between
      the groups as regards length of hospital stay or complications following
      ileostomy closure. Eighteen Seprafilm stoma patients and 22 conventional stoma
      patients received adjuvant chemotherapy. Median time to starting chemotherapy
      from resection was 10 versus 8.5 weeks, respectively (p = 0.36). CONCLUSIONS: An
      early stoma closure protocol facilitated by Seprafilm wrapping of the ileostomy
      is practical, does not increase morbidity and significantly reduces the time with
      a stoma for the patient. An early stoma closure protocol did not significantly
      delay in the commencement of chemotherapy.

PMID- 22618229
TI  - Near-infrared chemiluminescence tunable from 900 nm to 1700 nm from narrow
      bandgap compounds and polymers.
AB  - Near-infrared chemiluminescence tunable from 900 nm to 1700 nm was realized from
      the reaction of the narrow-bandgap compounds and polymers with oxalyl chloride
      and hydrogen peroxide. A prolonged chemiluminescent process can be achieved in
      solutions at low temperature or in polymer gels at room temperature.

PMID- 22618230
TI  - IL-7 splicing variant IL-7delta5 induces human breast cancer cell proliferation
      via activation of PI3K/Akt pathway.
AB  - Various tumor cells express interleukin 7 (IL-7) and IL-7 variants. IL-7 has been
      confirmed to stimulate solid tumor cell proliferation. However, the effect of IL
      7 variants on tumor cell proliferation remains unclear. In this study, we
      evaluated the role of IL-7delta5 (an IL-7 variant lacking exon 5) on
      proliferation and cell cycle progression of human MDA-MB-231 and MCF-7 breast
      cancer cells. The results showed that IL-7delta5 promoted cell proliferation and
      cell cycle progression from G1 phase to G2/M phase, associated with upregulation
      of cyclin D1 expression and the downregulation of p27(kip1) expression.
      Mechanistically, we found that IL-7delta5 induced the activation of Akt.
      Inhibition of PI3K/Akt pathway by LY294002 reversed the proliferation and cell
      cycle progression of MDA-MB-231 and MCF-7 cells induced by IL-7delta5. In
      conclusion, our findings demonstrate that IL-7delta5 variant induces human breast
      cancer cell proliferation and cell cycle progression via activation of PI3K/Akt
      pathway. Thus, IL-7delta5 may be a potential target for human breast cancer
      therapeutics intervention.

PMID- 22618231
TI  - Regulatory interplay between miR-21, JAG1 and 17beta-estradiol (E2) in breast
      cancer cells.
AB  - Overexpression of the oncomir miR-21 is associated with many cancers, including
      breast cancer. Elevated levels of Jagged-1 (JAG1), a predicted miR-21 target, are
      implicated in estrogen receptor negative (ER-) breast cancer. We demonstrate (by
      ablation of the miR-21 binding site in the JAG1 3'UTR) that miR-21 directly
      targets and represses JAG1 levels in MCF-7 (ER+) breast cancer cells. MiR-21
      targeting of JAG1 in MDA-MB-231 (ER-) breast cancer cells is dependent on miR-21
      dosage (levels). In both cell lines, miR-21 and JAG1 expression levels were
      negatively correlated due to their regulatory relationship. In addition, 17beta
      estradiol (E2) increases JAG1 levels by limiting (via downregulating miR-21
      levels) the repressive effects of miR-21 on the JAG1 3'UTR. Our results reveal a
      regulatory interplay between miR-21, JAG1 and E2 that is important for advancing
      understanding of how the oncogenic potential of miR-21 and JAG1 manifests in
      different sub-types of breast cancer.

PMID- 22618232
TI  - Preferential binding of IFI16 protein to cruciform structure and superhelical
      DNA.
AB  - Interferon (IFN)-inducible HIN-200 proteins play an important role in
      transcriptional regulation linked to cell cycle control, inflammation,
      autoimmunity and differentiation. IFI16 has been identified as a target of
      IFNalpha and gamma and is a member of the HIN-200 protein family. Expression
      level of IFI16 is often decreased in breast cancers, implicating its role as a
      tumor suppressor. As a potent transcription factor, IFI16 possesses a
      transcriptional regulatory region, a PYD/DAPIN/PAAD region which associates with
      IFN response, DNA-binding domains and binding regions for tumor suppressor
      proteins BRCA1 and p53. It is also reported that IFI16 protein is capable of
      binding p53 and cMYC gene promoters. Here, we demonstrate that IFI16 protein
      binds strongly to negatively superhelical plasmid DNA at a native superhelix
      density, as evidenced by electrophoretic retardation of supercoiled (sc) DNA in
      agarose gels. Binding of IFI16 to supercoiled DNA results in the appearance of
      one or more retarded DNA bands on the gels. After removal of IFI16, the original
      mobility of the scDNA is recovered. By contrast, IFI16 protein binds very weakly
      to the same DNA in linear state. Using short oligonucleotide targets, we also
      detect a strong preference for IFI16 binding to cruciform DNA structure compared
      to linear DNA topology. Hence, this novel DNA-binding property of IFI16 protein
      to scDNA and cruciform structures may play critical roles in its tumor suppressor
      function.

PMID- 22618233
TI  - Cellular infiltration on nanofibrous scaffolds using a modified electrospinning
      technique.
AB  - Electrospinning is currently used to fabricate nanofibrous scaffolds for tissue
      engineering applications. The major problem of these scaffolds is their
      intrinsically two-dimensional nature which inhibits cellular migration and in
      growth. In this study, we have introduced a modified setup of electrospinning to
      produce three-dimensional nanofibrous scaffolds which allows improved
      infiltration of cells. An array of focused halogen light bulbs was used to
      localize the heat in the path of electrospun jet near the collector. The
      fabricated mats were then seeded with cells in order to evaluate migration and
      infiltration. After 14 days of culture, a homogenous distribution of cells was
      observed throughout the scaffolds and showed the three-dimensional architecture
      of nanofibrous mats. By this novel and simple setup, the prepared electrospun
      mats will allow the seeded cells to obtain a three-dimensional arrangement which
      is ideal for tissue engineering applications.

PMID- 22618234
TI  - Crystal structure of Helicobacter pylori neutrophil-activating protein with a di
      nuclear ferroxidase center in a zinc or cadmium-bound form.
AB  - Helicobacter pylori neutrophil-activating protein (HP-NAP) is a Dps-like iron
      storage protein forming a dodecameric shell, and promotes adhesion of neutrophils
      to endothelial cells. The crystal structure of HP-NAP in a Zn(2+)- or Cd(2+)
      bound form reveals the binding of two zinc or two cadmium ions and their bridged
      water molecule at the ferroxidase center (FOC). The two zinc ions are coordinated
      in a tetrahedral manner to the conserved residues among HP-NAP and Dps proteins.
      The two cadmium ions are coordinated in a trigonal-bipyramidal and distorted
      octahedral manner. In both structures, the second ion is more weakly coordinated
      than the first. Another zinc ion is found inside of the negatively-charged
      threefold-related pore, which is suitable for metal ions to pass through.

PMID- 22618235
TI  - Impact of hypoxia, simulated ischemia and reperfusion in HL-1 cells on the
      expression of FKBP12/FKBP12.6 and intracellular calcium dynamics.
AB  - AIMS: To establish a cardiac cell culture model for simulated ischemia and
      reperfusion and in this model investigate the impact of simulated ischemia and
      reperfusion on expression of the calcium handling proteins FKBP12 and FKBP12.6,
      and intracellular calcium dynamics. METHODS: HL-1 cell cultures were exposed to
      normoxia (as control), hypoxia, simulated ischemia (HEDA) or HEDA+reactive oxygen
      species (ROS) for up to 24 h and after HEDA, with or without ROS, followed or not
      by simulated reperfusion (REPH) for 6 h. Viability was analyzed with a trypan
      blue exclusion method. Cell lysates were analyzed with real-time PCR and Western
      blot (WB) for FKBP12 and FKBP12.6. Intracellular Ca(2+)measurements were
      performed using dual-wavelength ratio imaging in fura-2 loaded cells. RESULTS: A
      time-dependent drop in viability was shown after HEDA (P<0.001). Viability was
      not further influenced by addition of ROS or REPH. The general patterns of FKBP12
      and FKBP12.6 mRNA expression showed upregulation after hypoxia, downregulation
      after ischemia and normalization after reperfusion, which was partially
      attenuated if ROS was added during HEDA. The protein contents were unaffected
      after hypoxia, tended to increase after ischemia and, for FKBP12.6, a further
      increase after reperfusion was shown. Hypoxia or HEDA, with or without REPH,
      resulted in a decreased amplitude of the Ca(2+) peak in response to caffeine. In
      addition, cells subjected to HEDA for 3 h or HEDA for 3 h followed by 6 h of REPH
      displayed irregular Ca(2+) oscillations with a decreased frequency. CONCLUSION: A
      threshold for cell survival with respect to duration of ischemia was established
      in our cell line model. Furthermore, we could demonstrate disturbances of calcium
      handling in the sarcoplasmic reticulum as well as alterations in the expressions
      of the calcium handling proteins FKBP12 and FKBP12.6, why this model may be
      suitable for further studies on ischemia and reperfusion with respect to calcium
      handling of the sarcoplasmic reticulum.

PMID- 22618236
TI  - Decalpenic acid induces early osteoblastic markers in pluripotent mesenchymal
      cells via activation of retinoic acid receptor gamma.
AB  - Decalpenic acid is a natural small molecule previously isolated from the
      fermentation broth of fungi that induces early osteoblastic markers in
      pluripotent mesenchymal cells. Treatment of mouse pluripotent mesenchymal
      C3H10T1/2 cells with decalpenic acid gave rise to a morphological change similar
      to that induced by the treatment with retinoic acid, i.e. the cells adopted a
      more elongated spindle shape. Using a retinoic acid response element reporter and
      receptor activity assays, we show that decalpenic acid is a new retinoid with
      selectivity towards retinoic acid receptors gamma and alpha. The induction of
      early osteoblastic markers by decalpenic acid was significantly inhibited by
      treatment with the retinoid antagonist, LE540, or with small interfering RNA
      mediated knockdown of retinoic acid receptor gamma. These results demonstrated
      that decalpenic acid induces early osteoblastic markers in pluripotent
      mesenchymal cells through activation of retinoic acid receptor gamma.

PMID- 22618237
TI  - Cross-linked enzyme aggregates of beta-glucosidase from Prunus domestica seeds.
AB  - Cross-linked enzyme aggregates (CLEAs) of beta-glucosidase were prepared and
      characterized. Under the optimum conditions, the activity recovery of CLEAs
      reached 84 %. The reduction by NaBH(4) resulted in slightly lower activities of
      CLEAs, while their thermostability was enhanced. CLEAs were more thermally stable
      than free enzyme (half lives, 973 vs. 518 min at 50  degrees C), while less
      stable than seed meal (half life, 1,090 min). In 90 % (v/v) t-butanol, the half
      lives of CLEAs and free enzyme were 53 and 6.7 h, respectively. Besides, the
      catalytic efficiency (V (max)/K (m)) of CLEAs was comparable to free enzyme (0.42
      vs. 0.47 min(-1) mg(-1)). This carrier-free immobilized enzyme had a network
      structure with multiple layers. The productivity of salidroside using CLEAs
      reached 150 g/l g catalyst, while being 6.3 g/l g with seed meal.

PMID- 22618238
TI  - Over-expression of stress protein-encoding genes helps Clostridium acetobutylicum
      to rapidly adapt to butanol stress.
AB  - The toxicity of n-butanol in microbial fermentations limits its formation. The
      stress response of Clostridium acetobutylicum involves various stress proteins
      and therefore, over-expression of genes encoding stress proteins constitutes an
      option to improve solvent tolerance. Over-expression of groESL, grpE and htpG,
      significantly improved butanol tolerance of C. acetobutylicum. Whereas the wild
      type and vector control strain did not survive 2 % (v/v) butanol for 2 h, the
      recombinant strains showed 45 % (groESL), 25 % (grpE) and 56 % (htpG),
      respectively, of the initial c.f.u. after 2 h of butanol exposure. As previously,
      over-expression of groESL led to higher butanol production rates, but the novel
      strains over-expressing grpE or htpG produced only 51 and 68 %, respectively, of
      the wild type butanol concentrations after 72 h clearly differentiating butanol
      tolerance and production. Not only butanol tolerance but also the adaptation to
      butanol in successive stress experiments was significantly facilitated by
      increased levels of GroESL, GrpE and HtpG. Re-transformation and sequence
      analyses of the plasmids confirmed that not the plasmids, but the host cells
      evolved to a more robust phenotype.

PMID- 22618239
TI  - Creation of a thermostable NADP+-dependent D-amino acid dehydrogenase from
      Ureibacillus thermosphaericus strain A1 meso-diaminopimelate dehydrogenase by
      site-directed mutagenesis.
AB  - A thermostable, NADP(+)-dependent D: -amino acid dehydrogenase (DAADH) was
      created from the meso-diaminopimelate dehydrogenase of Ureibacillus
      thermosphaericus strain A1 by introducing five point mutations into amino acid
      residues located in the active site. The recombinant protein, expressed in
      Escherichia coli, was purified to homogeneity using a two-step separation
      procedure and then characterized. In the presence of NADP(+), the protein
      catalyzed the oxidative deamination of several D: -amino acids, including D: 
      cyclohexylalanine, D: -isoleucine and D: -2-aminooctanoate, but not meso
      diaminopimelate, confirming the creation of a NADP(+)-dependent DAADH. For the
      reverse reaction, the corresponding 2-oxo acids were aminated in the presence of
      NADPH and ammonia. In addition, the D: -amino acid dehydrogenase showed no loss
      of activity at 65  degrees C, indicating the mutant enzyme was more thermostable
      than its parental meso-diaminopimelate dehydrogenase.

PMID- 22618240
TI  - Biosurfactants: a sustainable replacement for chemical surfactants?
AB  - Glycolipid biosurfactants produced by bacteria and yeasts provide significant
      opportunities to replace chemical surfactants with sustainable biologically
      produced alternatives in bulk commercial products such as laundry detergents and
      surface cleaners. Sophorolipids are already available in sufficient yield to make
      their use feasible while rhamnolipids and mannosylerythritol lipids require
      further development. The ability to tailor the biosurfactant produced to the
      specific needs of the product formulation will be an important future step.

PMID- 22618241
TI  - Strategic emission color tuning of highly fluorescent imidazole-based excited
      state intramolecular proton transfer molecules.
AB  - Highly fluorescent molecules harnessing the excited state intramolecular proton
      transfer (ESIPT) process are promising for a new generation of displays and light
      sources because they can offer very unique and novel optoelectronic properties
      which are different from those of conventional fluorescent dyes. To realize
      innovative ESIPT devices comprising full emission colors over the whole visible
      region, a molecular design strategy for predictable emission color tuning should
      be established. Here, we have developed a general strategy for a wide-range
      spectral tuning of imidazole-based ESIPT materials based on three different
      strategies--introduction of a nodal plane model, extension of effective
      conjugation length, and modification of heterocyclic rings. A series of nine
      ESIPT molecules were designed, synthesized and comprehensively investigated for
      their characteristic emission properties. All these molecules commonly showed no
      clear and transparent visible range absorption with no absorption color, but
      showed different colors of intense photoluminescence over broad visible regions
      from 450 nm (HPI) to 630 nm (HPNO) depending on their molecular structure. With
      the aid of density functional theory and time-dependent DFT calculations using
      M06, wB97XD, and B3LYP parameters with the 6-31G(d,p) basis set, these tuned
      emission bands of nine emitters were assigned from the stabilized excited state
      conformations that were derived from modified molecular structures.

PMID- 22618242
TI  - Purification and characterization of cytotoxin produced by a clinical isolate of
      Vibrio cholerae O54 TV113.
AB  - Vibrio cholerae O54 TV113 isolated from a diarrheal patient produces an
      extracellular cytotoxin that caused alteration in the morphology of Chinese
      hamster ovary cells manifested as cell shrinkage with intact cell boundaries and
      finally causing cell death. Syncase medium supplemented with lincomycin (50
      MUg/ml), pH 7.2, and 18 h incubation with shaking at 37  degrees C supported
      optimal cytotoxin production. We isolated and purified this cytotoxin to
      homogeneity by ultrafiltration, 40-80 % ammonium sulfate precipitation, gradient
      anion exchange chromatography, stepwise-anion exchange chromatography, and size
      exclusion chromatography increasing the specific activity by 866-fold. The
      cytotoxin is heat-labile, sensitive to protease and papain, and has a molecular
      weight of 64 kDa determined by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, and enterotoxic activity in rabbit ileal loop assay. Both
      cytotoxic and enterotoxic activity could be inhibited or neutralized by antiserum
      raised against purified cytotoxin but not by preimmune serum. Immunodiffusion
      test between purified cytotoxin and its antiserum gave a single well-defined
      precipitin band showing reaction of complete identity and a well-defined single
      band in an immunoblot assay. This study thus indicate that the cytotoxin
      expressed by strain TV113 has both cytotoxic and enterotoxic activity and appears
      to contribute in pathogenesis of non-O1, non-O139 strains.

PMID- 22618243
TI  - Possible cage-like nanostructures formed by amino acids.
AB  - We report possible cage-like nanostructures formed by a representative amino
      acid, serine octamers and decamers, determined by binding energy calculations and
      molecular dynamic simulations using the density functional tight-binding method.
      We used the l-handed serine to construct complex conformers linked by hydrogen
      bonds. We found the structures linked by -COOH...O=C- to be the most stable
      conformers and the calculation of the vibrational modes of complexes further
      illustrated this result. We attempted to apply our cage-like structures to the
      delivery of C(20) and cycloserine as model molecules. Our results may shed light
      on the design of cage-like biocompatible complexes for drug delivery.

PMID- 22618245
TI  - Targeting NOX enzymes in pulmonary fibrosis.
AB  - Oxidative stress has been associated with a number of human fibrotic diseases,
      including idiopathic pulmonary fibrosis (IPF). Oxidative stress is most often
      defined as an imbalance between the generation of reactive oxygen species (ROS)
      in excess of the capacity of cells/tissues to detoxify or scavenge them.
      Additionally, the regulated production of ROS participates in cellular signaling.
      Therapeutic strategies to treat IPF have, thus far, focused on augmenting anti
      oxidant capacity. Recent studies have demonstrated a critical role for ROS
      generating enzymatic systems, specifically, NADPH oxidase (NOX) family
      oxidoreductases in fibrotic processes. In this review, we examine the evidence
      for NOX isoforms in the generation and perpetuation of fibrosis, and the
      potential to target this gene family for the treatment of IPF and related
      fibrotic disorders.

PMID- 22618244
TI  - NADPH oxidases as therapeutic targets in ischemic stroke.
AB  - Reactive oxygen species (ROS) act physiologically as signaling molecules. In
      pathological conditions, such as ischemic stroke, ROS are released in excessive
      amounts and upon reperfusion exceed the body's antioxidant detoxifying capacity.
      This process leads to brain tissue damage during reoxygenation. Consequently,
      antioxidant strategies have long been suggested as a therapy for experimental
      stroke, but clinical trials have not yet been able to promote the translation of
      this concept into patient treatment regimens. As an evolution of this concept,
      recent studies have targeted the sources of ROS generation-rather than ROS
      themselves. In this context, NADPH oxidases have been identified as important
      generators of ROS in the cerebral vasculature under both physiological conditions
      in general and during ischemia/reoxygenation in particular. Inhibition of NADPH
      oxidases or genetic deletion of certain NADPH oxidase isoforms has been found to
      considerably reduce ischemic injury in experimental stroke. This review focuses
      on recent advances in the understanding of NADPH oxidase-mediated tissue injury
      in the cerebral vasculature, particularly at the level of the blood-brain
      barrier, and highlights promising inhibitory strategies that target the NADPH
      oxidases.

PMID- 22618247
TI  - Chromatin-remodeling complex specificity and embryonic vascular development.
AB  - Vascular development is a dynamic process that relies on the coordinated
      expression of numerous genes, but the factors that regulate gene expression
      during blood vessel development are not well defined. ATP-dependent chromatin
      remodeling complexes are gaining attention for their specific temporal and
      spatial effects on gene expression during vascular development. Genetic mutations
      in chromatin-remodeling complex subunits are revealing roles for the complexes in
      vascular signaling pathways at discrete developmental time points. Phenotypic
      analysis of these models at various stages of vascular development will continue
      to expand our understanding of how chromatin remodeling impacts new blood vessel
      growth. Such research could also provide novel therapeutic targets for the
      treatment of vascular pathologies. 

PMID- 22618246
TI  - What model organisms and interactomics can reveal about the genetics of human
      obesity.
AB  - Genome-wide association studies have identified a number of genes associated with
      human body weight. While some of these genes are large fields within obesity
      research, such as MC4R, POMC, FTO and BDNF, the majority do not have a clearly
      defined functional role explaining why they may affect body weight. Here, we
      searched biological databases and discovered 33 additional genes associated with
      human obesity (CADM2, GIPR, GPCR5B, LRP1B, NEGR1, NRXN3, SH2B1, FANCL, GNPDA2,
      HMGCR, MAP2K5, NUDT3, PRKD1, QPCTL, TNNI3K, MTCH2, DNAJC27, SLC39A8, MTIF3,
      RPL27A, SEC16B, ETV5, HMGA1, TFAP2B, TUB, ZNF608, FAIM2, KCTD15, LINGO2, POC5,
      PTBP2, TMEM18, TMEM160). We find that the majority have orthologues in distant
      species, such as D. melanogaster and C. elegans, suggesting that they are
      important for the biology of most bilateral species. Intriguingly, signalling
      cascade genes and transcription factors are enriched among these obesity genes,
      and several of the genes show properties that could be useful for potential drug
      discovery. In this review, we demonstrate how information from several distant
      model species, interactomics and signalling pathway analysis represents an
      important way to better understand the functional diversity of the surprisingly
      high number of molecules that seem to be important for human obesity.

PMID- 22618248
TI  - Mechanochemical and solution synthesis, X-ray structure and IR and 31P solid
      state NMR spectroscopic studies of copper(I) thiocyanate adducts with bulky
      monodentate tertiary phosphine ligands.
AB  - A number of adducts of copper(I) thiocyanate with bulky tertiary phosphine
      ligands, and some nitrogen-base solvates, were synthesized and structurally and
      spectroscopically characterised. CuSCN:PCy3 (1:2), as crystallized from pyridine,
      is shown by a single crystal X-ray study to be a one-dimensional polymer
      ...(Cy3P)2CuSCN(Cy3P)2CuSCN... (1) with the four-coordinate copper atoms linked
      end-on by S-SCN-N bridging thiocyanate groups. A second form (2), obtained from
      acetonitrile, was also identified and shown by IR and 31P CPMAS NMR spectroscopy
      to be mononuclear, with the magnitude of the dnu(Cu) parameter measured from the
      31P CPMAS and the nu(CN) value from the IR clearly establishing this compound as
      three-coordinate [(Cy3P)2CuNCS]. Two further CuSCN/PCy3 compounds CuSCN:PCy3
      (1:1) (3), and CuSCN:PCy3:py (1:1:1) (4) were also characterized
      spectroscopically, with the dnu(Cu) parameters indicating three- and four
      coordinate copper sites, respectively. Attempts to obtain a 1:2 adduct with tri-t
      butylphosphine have yielded, from pyridine, the 1:1 adduct as a dimer
      [(Bu(t)3P)((SCN)(NCS))Cu(PBu(t)3)] (5), while similar attempts with tri-o
      tolylphosphine (from acetonitrile and pyridine (= L)) resulted in solvated 1:1:1
      CuSCN:P(o-tol)3:L forms as dimeric [{(o-tol)3P}LCu((SCN)(NCS))CuL{P(o-tol)3}] (6
      and 8). The solvent-free 1:1 CuSCN:P(o-tol)3 adduct (7), obtained by desolvation
      of 6, was characterized spectroscopically and dnu(Cu) measurements from the 31P
      CPMAS NMR data are consistent with the decrease in coordination number of the
      copper atom from four (for 6) (P,N(MeCN)Cu,S,N) to three (for 7) (PCuS,N) upon
      loss of the acetonitrile of solvation. These results are compared with those
      previously reported for mononuclear and binuclear PPh3 adducts which demonstrate
      a clear tendency for the copper centre to remain four-coordinate. The IR
      spectroscopic measurements on these compounds show that bands in the far-IR
      spectra provide a much more definitive criterion for distinguishing between
      bridging and terminal bonding than does an often-used empirical rule based on
      nu(CN) in the mid-IR, which leads to the wrong conclusion in some cases.

PMID- 22618266
TI  - Assessing the risk of osteonecrosis of the jaw due to bisphosphonate therapy in
      the secondary prevention of osteoporotic fractures.
AB  - SUMMARY: There is evidence that the use oral bisphosphonates can lead to
      osteronecrosis of the jaws (ONJ). Although the occurrence of ONJ appears rare
      among oral bisphosphonates (BPs) users, it is important to know that it exists
      and can be opportunely minimized. INTRODUCTION: The purpose of this study is to
      evaluate the association between BPs prescribed for the secondary prevention of
      osteoporotic fractures and the occurrence of ONJ. METHODS: An Italian record
      linkage claims database with a target population of around 18 million individuals
      (6 million over 55 years of age) constituted the data source. We conducted a
      nested case-control study within a cohort of individuals aged 55+ years old, who
      were discharged from hospitals with a primary diagnosis of incident osteoporotic
      fracture. The date related to the discharge diagnosis of ONJ was the index date.
      Conditional logistic regression for matched data was fitted to estimate the odds
      ratio (OR) along with 95 % confidence intervals (95 % CI) for the likely
      association between use of BPs and the risk of ONJ. RESULTS: Any one of the 61
      ascertained cases of ONJ (incidence rate, 36.6 per 100,000 person-years) was
      matched to 20 controls for a total of 1120 controls. When the exposure to BPs was
      modeled according to recency (i.e., exposure time window prior to the index date)
      of use, the adjusted OR (95 % CI) for current users was 2.8 (1.3-5.9) against
      never users. The cumulative use of BPs has shown to increase the incidence of ONJ
      among patients with primary osteoporotic fractures, although not statistically
      significant risk has been observed. CONCLUSIONS: Although the risk of BP-related
      ONJ appears low in non-oncological indications, it is important to be aware that
      it exists and to know how it may be predicted and possibly minimized.

PMID- 22618267
TI  - Inhibition of osteoclast differentiation and matrix metalloproteinase production
      by CD4+CD25+ T cells in mice.
AB  - To reveal the mechanism of inflammation-accompanied osteoporosis, mouse CD11b
      cells and CD4+CD25+ T cells were cocultured. Our results showed that CD11b+
      monocytes cocultured with CD4+CD25+ T cells generated significantly less
      osteoclasts than those cocultured with CD4+CD25- T cells. The levels of MMP-7 and
      9 in coculture supernatant were decreased significantly when CD11b+ monocytes and
      CD4+CD25+ T cells were cocultured comparing to the CD4+CD25- T cell group. These
      results highlight the role of CD4+CD25+ T cells on rheumatic osteoporosis.
      INTRODUCTION: The purpose of this study was to reveal the mechanism of
      inflammation-accompanied osteoporosis by examining the effect of CD4+CD25+ T
      cells on osteoclast formation, as well as the production of matrix
      metalloproteinases (MMP)-2, 3, 7, and 9 from osteoclasts. METHODS: Mouse CD11b
      cells and CD4+CD25+ T cells were isolated using the microbead-based kits.
      Activated CD11b cells and CD4+CD25+ T were cocultured. CD4+CD25- T cells were
      used as controls. Osteoclasts were evaluated by counting the average of tartrate
      resistant acid phosphatase-positive multinucleated large cells among five high
      power fields (*200). After 2 days of coculture, supernatants were harvested for
      MMP measurement (by ELISA). RESULTS: At day 7, the CD11b+ monocytes cocultured
      with CD4+CD25+ T cells generated significantly (both p < 0.01) less osteoclasts
      (3.4 +/- 0.8) than those cocultured with CD4+CD25- T cells (16.2 +/- 1.3) and
      those cultured alone (16.2 +/- 2.7). The supernatant levels of MMP-7 and 9 were
      decreased significantly (p < 0.01) when CD11b+ monocytes and CD4+CD25+ T cells
      were cocultured compared to the other two conditions. CONCLUSIONS: The decreased
      CD4+CD25+ T cells may cause an overproduction of MMP-7 and 9 from osteoclasts,
      which highlight the role of CD4+CD25+ T cells on rheumatic osteoporosis.

PMID- 22618268
TI  - Bisphosphonate use and increased incidence of subtrochanteric fracture in South
      Korea: results from the National Claim Registry.
AB  - SUMMARY: We evaluated trends in the incidences of typical and atypical hip
      fracture in relation to bisphosphonate use in Korea from 2006 to 2010, using
      nationwide data obtained from the Health Insurance Review and Assessment Service
      (HIRA). INTRODUCTION: Recently, atypical hip fractures in the subtrochanteric
      region have been reported among patients on bisphosphonate. However, the
      association between atypical hip fracture and bisphosphonate is controversial. We
      evaluated trends in the incidences of typical and atypical hip fracture in
      relation to bisphosphonate use in Korea from 2006 to 2010, using nationwide data
      obtained from the HIRA. METHODS: All new visits or admissions to clinics or
      hospitals for a typical and atypical hip fractures were recorded nationwide by
      HIRA using the ICD-10 code classification. Typical and atypical hip fractures
      were defined as femoral neck/intertrochanteric and subtrochanteric fracture,
      respectively. Bisphosphonate prescription data were also abstracted from the HIRA
      database. RESULTS: The absolute number of typical and atypical hip fracture
      increased during the study period. Although age-adjusted incidence rates of
      typical hip fractures were stable in men and women, those of atypical hip
      fractures increased in women. Nationally, the annual numbers of prescriptions of
      bisphosphonate also increased during the study period. CONCLUSIONS: The results
      of this study suggest a possible causal relationship between bisphosphonate use
      and the increased incidence of atypical hip fracture in Korea.

PMID- 22618269
TI  - Prevalence of osteoporotic fracture risk factors and antiosteoporotic treatments
      in the Valencia region, Spain. The baseline characteristics of the ESOSVAL
      cohort.
AB  - This study provides information on the prevalence of the most important risk
      factors for osteoporosis and osteoporotic fracture in a large sample of women and
      men from the Valencia region and also provides the FRAX 10-year major and hip
      fracture risks for this population, as well as data about the use of diagnostic
      tests and antiosteoporotic treatments. INTRODUCTION: The purpose of this study
      was to describe demographic characteristics, osteoporosis risk factors, the 10
      year risk of osteoporotic fracture, and the use of densitometry and
      antiosteoporotic treatments in the Valencia region, Spain. METHODS: A cross
      sectional study using the ESOSVAL cohort baseline data was conducted. We analyze
      the data from 5,310 women and 5,725 men aged 50 and over who attended to 272
      collaborating primary care centers in 2009-2010. We collected the demographic,
      anthropometric, clinical, and pharmacy data from the electronic medical record.
      RESULTS: The mean age of participants was 64.3 years old for women and 65.6 years
      old for men. The most frequent fracture risk factors were sedentary life (22.2 %)
      and previous fracture (15.8 %) in women and low calcium intake (21.4 %) and
      current smoker (20.9 %) in men. According to FRAX((r)), the 10-year risk of
      presenting a major fracture was 5.5 % for the women and 2.8 % for the men. The 10
      year risk for hip fracture was 1.9 and 1.1 % for the women and the men,
      respectively; 23.8 % of the women and 5.2 % of the men had a densitometry test,
      27.7 % of the women and 3.5 % of the men were taking calcium and/or vitamin D
      supplements, and 28.2 % of the women (22.0 % in the 50-64 age group) and 2.3 % of
      the men were taking antiosteoporotic drugs. CONCLUSIONS: The prevalence of
      certain fracture risk factors not included in the FRAX tool (sedentary life,
      falls, low calcium intake) is high. In young women, their low risks estimated by
      FRAX contrast with the high figures for densitometry testing and treatment.

PMID- 22618271
TI  - Maternal tobacco smoke exposure during lactation inhibits catecholamine
      production by adrenal medullae in adult rat offspring.
AB  - Previously, we have shown that maternal smoke exposure during lactation, even
      when pups are not exposed, affects biochemical profiles in the offspring at
      weaning, eliciting lower body adiposity, hyperinsulinemia, hypocorticosteronemia
      and lower adrenal catecholamine content. However, the future impact of tobacco
      exposure is still unknown. As postnatal nicotine exposure causes short- and long
      term effects on pups' biochemistry and endocrine profiles, we have now evaluated
      some endocrine and metabolic parameters of the adult offspring whose mothers were
      tobacco exposed during lactation. For this, from day 3 to 21 of lactation, rat
      dams were divided in: 1) SE group, cigarette smoke-exposed (1.7 mg
      nicotine/cigarettes for 1 h, 4 times/day, daily), without their pups, and 2) C
      group, exposed to air, in the same conditions. Offspring were killed at 180-days
      old. Body weight and food intake were evaluated. Blood, white adipose tissue,
      adrenal, and liver were collected. All significant data were p<0.05. The adult SE
      offspring showed no change in body weight, cumulative food intake, serum hormone
      profile, serum lipid profile, or triglycerides content in liver. However, in
      adrenal gland, adult SE offspring showed lower catecholamine content ( - 50%) and
      lower tyrosine hydroxylase protein expression ( - 56%). Despite the hormonal
      alterations during lactation, tobacco smoke exposure through breast milk only
      programmed the adrenal medullary function at adulthood and this dysfunction can
      have consequence on stress response. Thus, an environment free of smoke during
      lactation period is essential to improve health outcomes in adult offspring.

PMID- 22618270
TI  - Nationwide, multicenter survey on the efficacy and safety of piperacillin for
      adult community-acquired pneumonia in Japan.
AB  - A survey on adult community-acquired pneumonia was conducted jointly by multiple
      centers nationwide to verify the Japanese Respiratory Society Guidelines for the
      Management of Community-Acquired Pneumonia in Adults (JRS2005). The efficacy and
      safety of piperacillin (PIPC) were investigated at the same time. PIPC is
      recommended as the initial treatment for patients with suspected bacterial
      pneumonia and pneumococcal pneumonia in JRS2005. Overall, 552 and 333 patients
      were registered for safety and efficacy analysis in this study, respectively. The
      majority of the cases in which PIPC was used had moderate disease (63.7 %), and
      the most common daily dosage was 4 g (73.6 %). The efficacy rate was 83.5 %
      overall, 81.1 % in patients with suspected bacterial pneumonia, and 92.8 % in
      patients with pneumococcal pneumonia. The efficacy rate with a daily dosage of 4
      g was 84.9 %, and the efficacy rates achieved with a daily dosage of 4 g in
      patients who had mild and moderate suspected bacterial pneumonia were 90.0 and
      82.6 %, respectively. The most commonly isolated causative organisms were
      Streptococcus pneumoniae (S. pneumoniae) and Haemophilus influenzae (H.
      influenzae), and the bacterial eradication rates were high (97.2 and 100 %,
      respectively). The incidence of adverse drug reactions was 5.62 %, among which
      the main events were hepatic dysfunction and decreased white blood cell count. In
      conclusion, this study showed that PIPC is safe and effective at 4 g/day for mild
      to-moderate adult community-acquired pneumonia.

PMID- 22618272
TI  - Plasma polymer coatings to aid retinal pigment epithelial growth for
      transplantation in the treatment of age related macular degeneration.
AB  - Subretinal transplantation of functioning retinal pigment epithelial (RPE) cells
      grown on a synthetic substrate is a potential treatment for age-related macular
      degeneration (AMD), a common cause of irreversible vision loss in developed
      countries. Plasma polymers give the opportunity to tailor the surface chemistry
      of the artificial substrate whilst maintaining the bulk properties. In this
      study, plasma polymers with different functionalities were investigated in terms
      of their effect on RPE attachment and growth. Plasma polymers of acrylic acid
      (AC), allyl amine (AM) and allyl alcohol (AL) were fabricated and characterised
      using X-ray photoelectron spectroscopy (XPS) and water contact angle
      measurements. Octadiene (OD) hydrocarbon films and tissue culture polystyrene
      were used as controls. Wettability varied from hydrophobic OD to relatively
      hydrophilic AC. XPS demonstrated four very different surfaces with the expected
      functionalities. Attachment, proliferation and morphological examination of an
      RPE cell line and primary RPE cells were investigated. Both cell types grew on
      all surfaces, with the exception of OD, although the proliferation rate of
      primary cells was low. Good epithelial morphology was also demonstrated. Plasma
      polymerised films show potential as cell carrier surfaces for RPE cells in the
      treatment of AMD.

PMID- 22618273
TI  - Structural tuning intra- versus inter-molecular proton transfer reaction in the
      excited state.
AB  - A series of 2-pyridyl-pyrazole derivatives 1-4 possessing five-membered ring
      hydrogen bonding configuration are synthesized, the structural flexibility of
      which is strategically tuned to be in the order of 1 > 2 > 3 > 4. This system
      then serves as an ideal chemical model to investigate the correlation between
      excited-state intramolecular proton transfer (ESIPT) reaction and molecular
      skeleton motion associated with hydrogen bonds. The resulting luminescence data
      reveal that the rate of ESIPT decreases upon increasing the structural
      constraint. At sufficiently low concentration where negligible dimerization is
      observed, ESIPT takes place in 1 and 2 but is prohibited in 3 and 4, for which
      high geometry constraint is imposed. The results imply that certain structural
      bending motions associated with hydrogen bonding angle/distance play a key role
      in ESIPT. This trend is also well supported by the DFT computational approach, in
      which the barrier associated with ESIPT is in the order of 1 < 2 < 3 < 4. Upon
      increasing the concentration in cyclohexane, except for 2, the rest of the title
      compounds undergo ground-state dimerization, from which the double proton
      transfer takes place in the excited state, resulting in a relatively blue shifted
      dimeric tautomer emission (cf. the monomer tautomer emission). The lack of
      dimerization in 2 is rationalized by substantial energy required to adjust the
      angle of hydrogen bond via twisting the propylene bridge prior to dimerization.

PMID- 22618274
TI  - Protic compound mediated living cross-chain-transfer polymerization of rac
      lactide: synthesis of isotactic (crystalline)-heterotactic (amorphous)
      stereomultiblock polylactide.
AB  - A highly efficient strategy for one-pot synthesis of programmable, crystalline
      amorphous stereomultiblock PLA from rac-lactide.

PMID- 22618275
TI  - Near room temperature dielectric transition in the perovskite formate framework
      [(CH3)2NH2][Mg(HCOO)3].
AB  - We report that the hybrid organic-inorganic compound [(CH3)2NH2][Mg(HCOO)3] shows
      a marked dielectric transition around Tt~ 270 K, associated to a structural phase
      transition from SG R3[combining macron]c (centrosymmetric) to Cc (non
      centrosymmetric). This is the highest Tt reported so far for a perovskite-like
      formate that is thus a promising candidate to display electric order very close
      to room temperature. 

PMID- 22618294
TI  - Generation of molecular complexity from cyclooctatetraene using dienyliron and
      olefin metathesis methodology.
AB  - Transformation of the simple hydrocarbon cyclooctatetraene into a variety of
      polycyclic skeletons was achieved by sequential coordination to iron, reaction
      with electrophiles followed by allylated nucleophiles, decomplexation and olefin
      metathesis.

PMID- 22618295
TI  - Single- and multiple-dose pharmacokinetics, safety and tolerability of zibotentan
      (ZD4054) in Chinese men with advanced solid tumors.
AB  - PURPOSE: The endothelin axis and the endothelin A (ET(A)) receptor have been
      implicated in tumor development and bone metastasis. This study aimed to
      investigate the pharmacokinetic (PK) and safety profiles of the specific ET(A)
      receptor antagonist, zibotentan, in elderly, male Chinese patients with advanced
      solid tumors. The PK data generated in these Chinese patients were further
      compared with those previously reported in Japanese and Caucasian patient
      populations. METHODS: In this Phase I, open-label study, patients received a
      single dose of zibotentan 10 mg on Day 1, followed by a 72-h washout period and
      12 consecutive days of once-daily zibotentan 10 mg. RESULTS: Fifteen patients
      received at least one dose of zibotentan 10 mg. Exposure was demonstrated in all
      patients and the PK profiles following single dosing and multiple dosing showed
      relatively rapid absorption, decline in a monophasic manner, a modest amount of
      accumulation, and relatively low apparent clearance and volume of distribution.
      Zibotentan was well tolerated with no new safety concerns. Adverse events
      reported in >1 patient were pyrexia (n = 4), constipation (n = 3), headache (n =
      3) and peripheral edema (n = 2). Comparative analysis found no evidence of
      significant differences in zibotentan exposure between the Chinese patients in
      our study, and the previous Japanese and Caucasian studies. CONCLUSIONS: The PK
      and safety profiles of zibotentan determined in this Chinese patient population
      are similar to those previously reported. Our findings suggest no clinically
      relevant inter-ethnic differences in zibotentan disposition between the patient
      populations analyzed.

PMID- 22618296
TI  - Complete remission within 2 years predicts a good prognosis after
      methylprednisolone pulse therapy in patients with IgA nephropathy.
AB  - BACKGROUND: Pozzi et al. reported the effectiveness of steroid pulse therapy
      (Pozzi's regimen) in IgA nephropathy (IgAN). The present study was performed to
      clarify the predictive factors for IgAN patients treated with Pozzi's regimen.
      METHODS: One hundred nine IgAN patients treated by Pozzi's regimen were observed
      for up to 112.6 (median 39.7) months, and remission of proteinuria (PR) and
      disappearance of urinary abnormalities [complete remission (CR)] after Pozzi's
      regimen were analyzed. Predictive factors for the glomerular filtration rate
      (GFR) slopes for up to 5 years were analyzed among 81 patients who were observed
      for at least 2 years. The outcome of a 50 % increase in sCr was compared between
      the CR and non-CR groups within 2 years. RESULTS: Cumulative PR and CR rates
      increased rapidly until 2 years (54.5 and 46.8 % at 2 years), and then slowly but
      steadily up to 6 years (72.8 and 66.4 % at 6 years). Baseline characteristics of
      the CR and non-CR groups within 2 years were similar except for proteinuria. GFR
      slope was steeper in the non-CR group than in the CR group (-2.44 +/- 5.12 vs. 
      0.32 +/- 3.34 ml/min/1.73 m(2)/year). On multivariate analysis, sex and CR within
      2 years were associated with GFR slope. Kaplan-Meier analysis demonstrated a
      better survival rate in CR group patients without a 50 % increase in sCr (p =
      0.024). CONCLUSIONS: Among IgAN patients treated with Pozzi's regimen, CR within
      2 years predicts a good prognosis.

PMID- 22618297
TI  - Gender differences in healthy life years within the EU: an exploration of the
      "health-survival" paradox.
AB  - OBJECTIVES: To evaluated the female-male health-survival paradox by estimating
      the contribution of women's mortality advantage versus women's disability
      disadvantage. METHODS: Disability prevalence was measured from the 2006 Survey on
      Income and Living Conditions in 25 European countries. Disability prevalence was
      applied to life tables to estimate healthy life years (HLY) at age 15. Gender
      differences in HLY were split into two parts: that due to gender inequality in
      mortality and that due to gender inequality in disability. The relationship
      between women's mortality advantage or disability disadvantage and the level of
      population health between countries was analysed using random-effects meta
      regression. RESULTS: Women's mortality advantage contributes to more HLY in
      women; women's higher prevalence of disability reduces the difference in HLY. In
      populations with high life expectancy women's advantage in HLY was small or even
      a men's advantage was found. In populations with lower life expectancy, the
      hardship among men is already evident at young ages. CONCLUSIONS: The results
      suggest that the health-survival paradox is a function of the level of population
      health, dependent on modifiable factors.

PMID- 22618298
TI  - Age-related changes in joint coordination during balance recovery.
AB  - Falls represent a significant health risk in the elderly and often result in
      injuries that require medical attention. Reduced ability to control motion of the
      whole-body center of mass (COM) has been shown to identify elderly people at risk
      of falling. To explore effective preventive strategies and interventions, we
      studied adult age-related differences in multijoint coordination to control the
      COM during balance recovery. We used the uncontrolled manifold (UCM) analysis,
      which can decompose movement variability of joints into good movement variability
      (motor equivalent) and bad movement variability (nonmotor equivalent). The good
      variability does not affect the COM position, while the bad variability does.
      Twenty-nine subjects, including 16 healthy young (26.1 +/- 4.5 year) and 13 older
      (74.6 +/- 5.6 year) adults without systematic disease, neurological disease, or a
      severe degenerative condition stood on a flat platform, and received an
      unexpected backward translation. The older adults had similar amounts of joint
      movement as the young adults during balance recovery except for the thoracic
      lumbar joint. However, the UCM analysis showed that the older adults changed
      their joint coordination pattern to control the COM and had a lower motor
      equivalent index with increased nonmotor equivalent variability (bad
      variability). We conclude that normal aging adults lose the compensatory strategy
      of flexibly controlling multiple joints when stabilizing the COM after receiving
      a balance perturbation.

PMID- 22618299
TI  - The reliability of manual reporting of clinical events in an anesthesia
      information management system (AIMS).
AB  - Manual incident reports significantly under-report adverse clinical events when
      compared with automated recordings of intraoperative data. Our goal was to
      determine the reliability of AIMS and CQI reports of adverse clinical events that
      had been witnessed and recorded by research assistants. The AIMS and CQI records
      of 995 patients aged 2-12 years were analyzed to determine if anesthesia
      providers had properly documented the emesis events that were observed and
      recorded by research assistants who were present in the operating room at the
      time of induction. Research assistants recorded eight cases of emesis during
      induction that were confirmed with the attending anesthesiologist at the time of
      induction. AIMS yielded a sensitivity of 38 % (95 % confidence interval [CI] 8.5
      75.5 %), while the sensitivity of CQI reporting was 13 % (95 % CI 0.3-52.7 %).
      The low sensitivities of the AIMS and CQI reports suggest that user-reported AIMS
      and CQI data do not reliably include significant clinical events.

PMID- 22618300
TI  - Construction and analysis of an intergeneric fusant able to degrade bensulfuron
      methyl and butachlor.
AB  - Rhodococcus sp. BX2 degrades bensulfuron-methyl but not butachlor, and
      Acinetobacter sp. LYC-1 degrades butachlor but not bensulfuron-methyl. Functional
      strains were constructed through protoplast fusion of Rhodococcus sp. BX2 and
      Acinetobacter sp. LYC-1 to generate fusants with an improved ability to
      simultaneously degrade bensulfuron-methyl and butachlor. Initial identification
      and stability tests of the fusants were performed. Three fusants with eighth
      transfer on plates containing two antibiotics and two herbicides were obtained.
      F1 also grew well in an inorganic salt solution containing bensulfuron-methyl and
      butachlor. F1 was characterized by its parents' morphological and physio
      biochemical features. F1 not only had bands in common with BX2 and LYC-1, but
      also had its own specific bands analyzed by Random Amplified Polymorphic DNA. The
      genetic similarity indices between F1 and BX2 and F1 and LYC-1 were 0.507 and
      0.470, respectively. The percentages bensulfuron-methyl and butachlor degradation
      by F1 in an inorganic salt solution supplemented with 100 mg/L bensulfuron-methyl
      and 100 mg/L butachlor were 65.35 and 62.41 %, respectively, and the percentages
      in soil contaminated with 10 mg/kg bensulfuron-methyl and 10 mg/kg butachlor with
      an inoculum size of 5 % at 34  degrees C and at a pH of 7.5 after 35 days were
      63.74 and 61.53 %, respectively. It was demonstrated that F1 could simultaneously
      degrade bensulfuron-methyl and butachlor.

PMID- 22618301
TI  - Mitochondrial neurogastrointestinal encephalomyopathy: novel pathogenic mutations
      in thymidine phosphorylase gene in two Italian brothers.
AB  - Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE, MIM 603041) is an
      autosomal recessive multisystem disorder occurring due to mutations in a nuclear
      gene coding for the enzyme thymidine phosphorylase (TYMP). Clinical features of
      MNGIE include gastrointestinal dysmotility, cachexia, ptosis or ophthalmoparesis,
      peripheral neuropathy, diffuse leukoencephalopathy, and signs of mitochondrial
      dysfunction in tissues. We report the clinical and molecular findings in two
      brothers in whom novel TYMP gene mutations (c.215-13_215delinsGCGTGA; c.1159 + 2T
      > A) were associated with different clinical presentations and outcomes.

PMID- 22618302
TI  - Subclinical hypothyroidism during valproic acid therapy in children and
      adolescents with epilepsy.
AB  - The aim of this study was to evaluate the incidence of thyroid dysfunction during
      valproic acid (VPA) therapy in children and adolescents with epilepsy. The serum
      levels of thyroid-stimulating hormone (TSH), free thyroxine, and triiodothyronine
      were evaluated in 61 children with epilepsy who received VPA monotherapy for more
      than 6 months and in 144 controls. We analyzed the effect of age, seizure type,
      duration of VPA treatment, dose of VPA, and serum level of VPA on thyroid
      function. The incidence of subclinical hypothyroidism was significantly higher in
      patients with VPA therapy than in controls (52.4 vs. 16.7%; p < 0.001). In
      addition, of the 61 patients, 5 (8.1%) exhibited TSH levels that were >10
      MUIU/mL. However, none of the patients and controls showed overt hypothyroidism.
      Serum VPA level and daily dose of VPA were correlated with TSH level. Subclinical
      hypothyroidism developed frequently in children and adolescents during VPA
      therapy.

PMID- 22618303
TI  - Free-running circadian rhythms of muscle strength, reaction time, and body
      temperature in totally blind people.
AB  - Light is the major synchronizer of circadian rhythms. In the absence of light, as
      for totally blind people, some variables, such as body temperature, have an
      endogenous period that is longer than 24 h and tend to be free running. However,
      the circadian rhythm of muscle strength and reaction time in totally blind people
      has not been defined in the literature. The objective of this study was to
      determine the period of the endogenous circadian rhythm of the isometric and
      isokinetic contraction strength and simple reaction time of totally blind people.
      The study included six totally blind people with free-running circadian rhythms
      and four sighted people (control group). Although the control group required only
      a single session to determine the circadian rhythm, the blind people required
      three sessions to determine the endogenous period. In each session, isometric
      strength, isokinetic strength, reaction time, and body temperature were collected
      six different times a day with an interval of at least 8 h. The control group had
      better performance for strength and reaction time in the afternoon. For the
      blind, this performance became delayed throughout the day. Therefore, we conclude
      that the circadian rhythms of strength and simple reaction time of totally blind
      people are within their free-running periods. For some professionals, like the
      blind paralympic athletes, activities that require large physiological capacities
      in which the maximum stimulus should match the ideal time of competition may
      result in the blind athletes falling short of their expected performance under
      this free-running condition.

PMID- 22618304
TI  - Effects of high-intensity and blood flow-restricted low-intensity resistance
      training on carotid arterial compliance: role of blood pressure during training
      sessions.
AB  - We examined the effects of high-intensity resistance training (HIT) and low
      intensity blood flow-restricted (LI-BFR) resistance training on carotid arterial
      compliance. Nineteen young men were randomly divided into HIT (n = 9) or LI-BFR
      (n = 10) groups. The HIT and LI-BFR groups performed 75 and 30 %, respectively,
      of one-repetition maximum (1-RM) bench press exercise, 3 days per week for 6
      weeks. During the training sessions, the LI-BFR group wore elastic cuffs around
      the most proximal region of both arms. Muscle cross-sectional area (CSA), 1-RM
      strength, and carotid arterial compliance were measured before and 3 days after
      the final training session. Acute changes in systolic arterial pressure (SAP),
      plasma endothelin-1 (ET-1), nitrite/nitrate (NOx), and noradrenalin
      concentrations were also measured during and after a bout of training session.
      The training led to significant increases (P < 0.01) in bench press 1-RM and arm
      and chest muscle CSA in the two training groups. Carotid arterial compliance
      decreased significantly (P < 0.05) in the HIT group, but not in the LI-BFR group.
      There was a significant correlation (r = -0.533, P < 0.05) between the change in
      carotid arterial compliance and the acute change in SAP during training sessions;
      however, ET-1 and NOx did not correlate with carotid arterial compliance. Our
      results suggest that muscle CSA and strength increased following 6 weeks of both
      HIT and LI-BFR training. However, carotid arterial compliance decreased in only
      the HIT group, and the changes were correlated with SAP elevations during
      exercise sessions.

PMID- 22618306
TI  - The latent structure of medically unexplained symptoms and its relation to
      functional somatic syndromes.
AB  - BACKGROUND: Medically unexplained symptoms are the hallmark of somatoform
      disorders and functional somatic syndromes. PURPOSE: Although medically
      unexplained symptoms represent a common phenomenon both in the general population
      as well as in medical settings, the exact latent structure of somatic symptoms
      remains largely unclear. METHOD: We examined the latent structure of medically
      unexplained symptoms by means of the Patient Health Questionnaire-15 (PHQ-15)
      questionnaire (i.e., a popular symptom checklist) and provide support for the
      construct validity of our model. The data were analyzed using confirmatory factor
      analysis in a general population sample (study 1; N = 414) and in a sample of
      primary care patients (study 2; N = 308). We compared four different latent
      structure models of medically unexplained symptoms: a general factor model, a
      correlated group factor model, a hierarchical model, and a bifactor model.
      RESULTS: In study 1, a bifactor model with one general factor and four
      independent specific symptom factors (i.e., gastrointestinal, pain, fatigue, and
      cardiopulmonary symptoms) showed the best model fit. This bifactor model was
      confirmed in the primary care sample (study 2). Additionally, the model explained
      59 % of the variance of the irritable bowel syndrome (IBS). In this structural
      equation model, both the general factor (14 %) as well as the gastrointestinal
      symptom factor (42 %) significantly predicted the IBS. CONCLUSION: The findings
      of both studies help to clarify the latent structure of somatic symptoms in the
      PHQ-15. The bifactor model outperformed alternative models and demonstrated
      external validity in predicting IBS.

PMID- 22618307
TI  - Association of multimodal treatment-induced improvements in stress, exercise
      volume, nutrition, and weight with improved blood pressure in severely obese
      women.
AB  - BACKGROUND: Research suggests that obesity, physical inactivity, anxiety
      (psychological tension), and a poor diet are associated with high blood pressure
      (BP). Although medication is the treatment of choice, behavioral methods might
      also improve BP in individuals with both prehypertension and hypertension.
      METHODS: Severely obese women from the southeast USA (N = 155; M(age) = 45 years;
      M(body mass index) (BMI) = 41 kg/m(2)) that fulfilled criteria for either
      prehypertension (n = 96) or hypertension (n = 59) volunteered for a Young Men's
      Christian Association-based exercise and nutrition support treatment that also
      included instruction in stress-management methods. RESULTS: Significant (p values
      of <=0.001) within-group improvements over 26 weeks in tension, overall mood,
      exercise volume, fruit and vegetable consumption, BMI, and systolic and diastolic
      BP were found. There were significant (p values of <0.05) bivariate correlations
      between improvements in tension, overall mood, volume of exercise, fruit and
      vegetable intake, BMI, and systolic and diastolic BP improvements. Multiple
      regression analyses, separately entering changes in tension and overall mood
      along with changes in volume of exercise, fruit and vegetable intake, and BMI,
      explained 19 and 20 % of the variances in systolic BP, respectively, (p values of
      <0.001) and 8 % of the variances, each (p values of <=0.02), in diastolic BP. In
      each multiple regression equation, improvements in the psychological factors of
      tension and overall mood demonstrated the greatest independent contribution to
      the variances accounted for in BP improvements. CONCLUSIONS: The ability of
      nonpharmaceutical, behavioral methods to improve BP in women with prehypertension
      and hypertension was suggested, with changes in the psychological factors of
      tension and overall mood appearing to be especially salient. Practical
      applications of findings were suggested.

PMID- 22618308
TI  - Mindfulness-based stress reduction for the treatment of irritable bowel syndrome
      symptoms: a randomized wait-list controlled trial.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a functional disorder of the lower
      gastrointestinal (GI) tract affected by stress, which may benefit from a
      biopsychosocial treatment approach such as mindfulness-based stress reduction
      (MBSR). PURPOSE: A treatment as usual (TAU) wait-list controlled trial was
      conducted in Calgary, Canada to investigate the impact of MBSR on IBS symptoms.
      It was hypothesized that MBSR patients would experience greater reduction in
      overall IBS symptom severity and self-reported symptoms of stress relative to
      control patients. METHOD: Ninety patients diagnosed with IBS using the Rome III
      criteria were randomized to either an immediate MBSR program (n = 43) or to wait
      for the next available program (n = 47). Patients completed IBS symptom severity,
      stress, mood, quality of life (QOL), and spirituality scales pre- and post
      intervention or waiting period and at 6-month follow-up. Intent-to-treat linear
      mixed model analyses for repeated measures were conducted, followed by completers
      analyses. RESULTS: While both groups exhibited a decrease in IBS symptom severity
      scores over time, the improvement in the MBSR group was greater than the controls
      and was clinically meaningful, with symptom severity decreasing from constantly
      to occasionally present. Pre- to post-intervention dropout rates of 44 and 23 %
      for the MBSR and control groups, respectively, were observed. At 6-month follow
      up, the MBSR group maintained a clinically meaningful improvement in overall IBS
      symptoms compared to the wait-list group, who also improved marginally, resulting
      in no statistically significant differences between groups at follow-up.
      Improvements in overall mood, QOL, and spirituality were observed for both groups
      over time. CONCLUSIONS: The results of this trial provide preliminary evidence
      for the feasibility and efficacy of a mindfulness intervention for the reduction
      of IBS symptom severity and symptoms of stress and the maintenance of these
      improvements at 6 months post-intervention. Attention and self-monitoring and/or
      anticipation of MBSR participation may account for smaller improvements observed
      in TAU patients.

PMID- 22618310
TI  - Duloxetine blocks cloned Kv4.3 potassium channels.
AB  - The effects of duloxetine were examined on cloned Kv4.3 channels stably expressed
      in CHO cells using the whole-cell patch-clamp technique. Duloxetine decreased the
      peak amplitude of Kv4.3 currents with an acceleration of the decay rate of
      current inactivation in a concentration-dependent manner. The IC(50) values
      required for the blocking effects of duloxetine on the peak amplitude and the
      integral of currents were 8.4 and 2.1MUM, respectively. Duloxetine accelerated
      the rate of inactivation of Kv4.3 currents and thereby decreased the time-to-peak
      in a concentration-dependent manner. Analysis of the time dependence of the drug
      block produced estimates of 21.9MUM(-1)s(-1) and 165.9s(-1), for the respective
      association (k(+1)) and dissociation (k(-1)) rate constants. The K(d) value (k(
      1)/k(+1)) yielded 7.5MUM, which approximates the experimental IC(50) value
      obtained from the concentration-response curve. The block of Kv4.3 by duloxetine
      was voltage-dependent at a membrane potential coinciding with the activation of
      the channels. At a more positive potential, however, the block was relieved.
      Duloxetine produced a hyperpolarizing shift in the voltage dependence of the
      steady-state inactivation of Kv4.3, and accelerated the closed-state inactivation
      of Kv4.3 in the subthreshold voltage range. Duloxetine induced a significant use
      dependent block at frequencies of 1 and 2Hz. In the presence of duloxetine, the
      recovery from inactivation was slower than under control conditions. These
      results demonstrate that duloxetine exerts a concentration-dependent block of
      Kv4.3 by binding to the channels in the open and inactivated states and these
      actions may contribute to its analgesic effect in neuropathic pain.

PMID- 22618309
TI  - Interactions and phosphorylation of postsynaptic density 93 (PSD-93) by
      extracellular signal-regulated kinase (ERK).
AB  - Postsynaptic density 93 (PSD-93) is a protein enriched at postsynaptic sites. As
      a key scaffolding protein, PSD-93 forms complexes with the clustering of various
      synaptic proteins to construct postsynaptic signaling networks and control
      synaptic transmission. Extracellular signal-regulated kinase (ERK) is a
      prototypic member of a serine/threonine protein kinase family known as mitogen
      activated protein kinase (MAPK). This kinase, especially ERK2 isoform, noticeably
      resides in peripheral structures of neurons, such as dendritic spines and
      postsynaptic density areas, in addition to its distribution in the cytoplasm and
      nucleus, although little is known about specific substrates of ERK at synaptic
      sites. In this study, we found that synaptic PSD-93 is a direct target of ERK.
      This was demonstrated by direct protein-protein interactions between purified
      ERK2 and PSD-93 in vitro. The accurate ERK2-binding region seems to locate at an
      N-terminal region of PSD-93. In adult rat striatal neurons in vivo, native ERK
      from synaptosomal fractions also associated with PSD-93. In phosphorylation
      assays, active ERK2 phosphorylated PSD-93. An accurate phosphorylation site was
      identified at a serine site (S323). In striatal neurons, immunoprecipitated PSD
      93 showed basal phosphorylation at an ERK-sensitive site. Our data provide
      evidence supporting PSD-93 as a new substrate of the synaptic species of ERK.
      ERK2 possesses the ability to interact with PSD-93 and phosphorylate PSD-93 at a
      specific site.

PMID- 22618326
TI  - Two-dimensional flow magnetophoresis of microparticles.
AB  - A new two-dimensional micro-flow magnetophoresis device was constructed in a
      superconducting magnet (10 T) using triangular shaped pole pieces, which could
      apply a magnetic strength, B(dB/dx), in the range of ca. 0-14,000 T(2) m(-1)
      across a capillary cell. Polystyrene particles with diameters of 1, 3, and 6 MUm
      were used as test samples in a paramagnetic medium of 1 M MnCl(2) to evaluate the
      performance of this method. Microparticles migrated across the capillary along
      the edge of the pole pieces, and then flowed through the gap in the pole piece at
      a position defined as the migration distance, depending on the magnetic
      susceptibility and the size of particles as well as the flow rate. The most
      effective flow rate to exhibit the largest resolution among the particles was
      theoretically predicted and experimentally confirmed. By this method, the
      magnetic susceptibilities of individual deoxygenated and non-deoxygenated red
      blood cells were measured from the relative migration distance.

PMID- 22618327
TI  - Highly sensitive and selective measurement of underivatized methylmalonic acid in
      serum and plasma by liquid chromatography-tandem mass spectrometry.
AB  - Methylmalonic acid (MMA) is a functional biomarker of vitamin B12 deficiency.
      Measurement of plasma MMA is challenging due to its small molecular weight and
      hydrophilic nature. Several liquid chromatography-tandem mass spectrometry (LC
      MS/MS) methods have been developed for measuring plasma MMA. However, these
      methods involve lengthy sample preparation, long chromatographic run time,
      inadequate sensitivity, or interference from succinic acid (SA). Here we report a
      novel LC-MS/MS method for quantitation of underivatized MMA in serum or
      heparinized plasma with high sensitivity and selectivity. Sample preparation
      involved only strong anion exchange solid phase extraction. The extract was
      purified by online turbulent flow and analyzed on an Organic Acids column. MS/MS
      analysis was performed in negative electrospray mode, and the analytical time was
      6 min. The use of ion ratio confirmation in combination with chromatographic
      resolution from SA greatly enhanced the selectivity. No interference was
      observed. This method was linear from 26.2 to 26,010.0 nM with an accuracy of 98
      111 %. Total coefficient of variation was less than 4.6 % for three concentration
      levels tested. Comparison with a reference laboratory LC-MS/MS method using
      leftover patient serum specimens (n = 48) showed a mean bias of -2.3 nM (-0.61 %)
      with a Deming regression slope of 1.016, intercept of -6.6 nM, standard error of
      estimate of 25.3 nM, and a correlation coefficient of 0.9945. In conclusion, this
      LC-MS/MS method offers highly sensitive and selective quantitation of MMA in
      serum and plasma with simple sample preparation.

PMID- 22618328
TI  - Chromatographic retention behaviour, modelling and separation optimisation of the
      quaternary ammonium salt isometamidium chloride and related compounds on a range
      of reversed-phase liquid chromatographic stationary phases.
AB  - This paper describes the reversed-phase liquid chromatographic behaviour of the
      trypanocidal quaternary ammonium salt isometamidium chloride and its related
      compounds on a range of liquid chromatographic phases possessing alkyl and phenyl
      ligands on the same inert silica. In a parallel study with various extended polar
      selectivity phases which possessed different hydrophobic/silanophilic (hydrogen
      bonding) activity ratios, the chromatographic retention/selectivities of the
      quaternary ammonium salts was shown to be due to a co-operative mechanism between
      hydrophobic and silanophilic interactions. The highly aromatic and planar
      isometamidium compounds were found to be substantially retained on stationary
      phases containing aromatic functionality via strong pi-pi interactions. The
      chemometric approach of principal component analysis was used to characterise the
      chromatographic behaviour of the isometamidium compounds on the differing phases
      and to help identify the dominant retention mechanism(s). Two-dimensional
      (temperature/gradient) retention modelling was employed to develop and optimise a
      rapid liquid chromatography method for the separation of the six quaternary
      ammonium salts within 2.5 min which would be suitable for bioanalysis using
      liquid chromatography-mass spectrometry. This is the first reported systematic
      study of the relationship between stationary phase chemistries and
      retention/selectivity for a group of quaternary ammonium salts.

PMID- 22618329
TI  - Recrudescent digoxin toxicity treated with plasma exchange: a case report and
      review of literature.
AB  - A 53-year-old woman presented with digitalis toxicity caused by acute overdose
      that manifested as atrial tachycardia with block, sinus pauses, and competing AV
      junctional rhythm with atrial fibrillation. Patient admitted to overdosing with
      digoxin 15-20 h before presentation with intent to commit suicide. Serum digoxin
      level was 35.6 ng/ml and renal function was normal. Patient was treated with
      1,040 mg of digoxin-specific antibody Fab fragment with prompt resolution of
      arrhythmias and restoration of sinus rhythm. Four hours after digoxin antibody
      administration, serum digoxin level declined to 0.2 ng/ml. Eighteen hours after
      treatment with Fab fragment, patient developed premature ventricular complexes,
      atrial tachycardia with and without atrioventricular block, and non-sustained
      ventricular tachycardia followed by ventricular fibrillation from which she was
      successfully resuscitated. Electrocardiogram showed no evidence of acute
      myocardial infarction, and emergent coronary angiogram did not reveal significant
      coronary artery disease. Repeat digoxin level was 20.4 ng/ml. A diagnosis of
      recrudescent digoxin toxicity was made and the patient was treated with one
      session of plasma exchange with resolution of arrhythmias. Immediately after
      plasma exchange, digoxin level decreased to 10.4 ng/ml, and after 10 h, the level
      further decreased to 6.6 ng/ml. The following day, digoxin level had decreased to
      2.9 ng/ml. Our experience with this case would suggest that plasma exchange
      should be considered as a treatment modality for recrudescent digoxin toxicity.

PMID- 22618330
TI  - Doxorubicin-induced changes of ventricular repolarization heterogeneity: results
      of a chronic rat study.
AB  - Anthracycline chemotherapy produces cardiac repolarization abnormalities and
      arrhythmias because of cardiac toxicity of drugs. Ventricular arrhythmogenesis is
      attributable to increase in repolarization heterogeneity that is characterized by
      spatial dispersion of repolarization. The purpose of this work was to study the
      delayed effects of doxorubicin, the most frequently used anthracycline, on
      repolarization heterogeneity of the ventricular epicardium. Doxorubicin was
      administered to rats in a cumulative dose of 15 mg/kg (six equal intraperitoneal
      injections over a period of 2 weeks). Six weeks after the last injection,
      electrophysiological mapping of the ventricular epicardium was performed by
      sequential superimposition of a 64-electrode array on the left ventricular base,
      left ventricular apex, right ventricular base, and right ventricular apex.
      Activation-recovery intervals (ARIs) were measured. In doxorubicin-treated rats,
      ARIs were inhomogeneously prolonged, the overall ARI dispersion and local ARI
      dispersions were increased, and the interregional differences in ARI dispersion
      were decreased. These data demonstrate that doxorubicin-induced inhomogeneous
      prolongation of repolarization of the ventricular epicardium results in
      increasing heterogeneity of ventricular repolarization because of increasing
      intraregional heterogeneity while interregional differences are lost.
      Repolarization of the right ventricle is more sensitive to doxorubicin than that
      of the left one.

PMID- 22618331
TI  - Rhodium-catalysed linear-selective alkyne hydroacylation.
AB  - The use of the electron-rich diphosphine ligand, dcpe, allows the efficient and
      highly linear selective hydroacylative coupling of aldehydes, including aryl
      examples, with a range of alkynes.

PMID- 22618332
TI  - Oxidation of dimethyldi(2-pyridyl)borato Pt(II)Me(n) complexes, n = 1, 0, with
      H2O2: tandem B-to-Pt methyl group migration and formation of C-O bond.
AB  - New dimethyldi(2-pyridyl)borato (dmdpb) platinum(II) complexes,
      (dmdpb)Pt(II)Me(SMe(2)) (1), (dmdpb)Pt(II)(L)(SMe(2))(+), L = MeOH (2), MeCN (3),
      supported by dimethylsulfide ligand and featuring one (1) or no hydrocarbyls at
      the metal (2, 3) were prepared and their oxidation with hydrogen peroxide was
      studied. Both complex 1 bearing the formal charge of +1 on the metal and the
      methanol complex 2 capable of losing the proton of the methanol ligand to form
      the methoxide derivative 4 charged similarly to 1, are reactive towards H(2)O(2).
      However, the cationic complex 3 with a formal charge of +2 on the metal does not
      react with H(2)O(2). The oxidation of the monomethyl platinum(II) complex 1 leads
      to the B-to-Pt methyl transfer and formation of a robust dimethyl Pt(IV) species
      5 which does not undergo C-O reductive elimination up to 100  degrees C. By
      contrast, oxidation of 2 in methanol-d(4) leads to quantitative formation of
      dimethyl ether-d(3), CD(3)OCH(3). It was presumed that the latter reaction
      involves the B-to-Pt methyl transfer and formation of a highly reactive cationic
      monomethyl Pt(IV) species whose methyl group carbon atom can accept nucleophilic
      attack by the methanol-d(4) solvent to form dimethyl ether-d(3).

PMID- 22618350
TI  - One-pot synthesis of 2-aminoquinoline-based alkaloids from acetonitrile.
AB  - alpha-Diaminoboryl carbanions, readily prepared from acetonitrile,
      stereoselectively convert 2-nitrobenzaldehydes into nitrophenyl (Z)
      acrylonitriles. Subsequent reductive cyclization leads to a series of 2
      aminoquinoline derivatives. The entire procedure is practically operated in a
      single flask.

PMID- 22618351
TI  - Efficiency enhancement in dye sensitized solar cells using gel polymer
      electrolytes based on a tetrahexylammonium iodide and MgI2 binary iodide system.
AB  - Quasi-solid-state dye-sensitized solar cells have drawn the attention of
      scientists and technologists as a potential candidate to supplement future energy
      needs. The conduction of iodide ions in quasi-solid-state polymer electrolytes
      and the performance of dye sensitized solar cells containing such electrolytes
      can be enhanced by incorporating iodides having appropriate cations. Gel-type
      electrolytes, based on PAN host polymers and mixture of salts tetrahexylammonium
      iodide (Hex4N(+)I(-)) and MgI2, were prepared by incorporating ethylene carbonate
      and propylene carbonate as plasticizers. The salt composition in the binary
      mixture was varied in order to optimize the performance of solar cells. The
      electrolyte containing 120% Hex4N(+)I(-) with respect to weight of PAN and
      without MgI2 showed the highest conductivity out of the compositions studied, 2.5
      * 10(-3) S cm(-1) at 25  degrees C, and a glass transition at -102.4  degrees C.
      However, the electrolyte containing 100% Hex4N(+)I(-) and 20% MgI2 showed the
      best solar cell performance highlighting the influence of the cation on the
      performance of the cell. The predominantly ionic behaviour of the electrolytes
      was established from the dc polarization data and all the electrolytes exhibit
      iodide ion transport. Seven different solar cells were fabricated employing
      different electrolyte compositions. The best cell using the electrolyte with 100%
      Hex4N(+)I(-) and 20% MgI2 with respect to PAN weight showed 3.5% energy
      conversion efficiency and 8.6 mA cm(-2) short circuit current density. 

PMID- 22618353
TI  - Selective one-pot synthesis of symmetrical and unsymmetrical di- and
      triarylamines with a ligandless copper catalytic system.
AB  - The one-pot synthesis of symmetrical or unsymmetrical di- or triarylamines using
      aryl iodides or bromides and LiNH(2) as ammonia source is reported. This highly
      selective method is based, for the first time, on a copper-catalyzed system,
      which does not require the presence of any additional ligand.

PMID- 22618352
TI  - Auditory cortex signs of age-related hearing loss.
AB  - Age-related hearing loss, or presbyacusis, is a major public health problem that
      causes communication difficulties and is associated with diminished quality of
      life. Limited satisfaction with hearing aids, particularly in noisy listening
      conditions, suggests that central nervous system declines occur with presbyacusis
      and may limit the efficacy of interventions focused solely on improving
      audibility. This study of 49 older adults (M = 69.58, SD = 8.22 years; 29 female)
      was designed to examine the extent to which low and/or high frequency hearing
      loss was related to auditory cortex morphology. Low and high frequency hearing
      constructs were obtained from a factor analysis of audiograms from these older
      adults and 1,704 audiograms from an independent sample of older adults.
      Significant region of interest and voxel-wise gray matter volume associations
      were observed for the high frequency hearing construct. These effects occurred
      most robustly in a primary auditory cortex region (Te1.0) where there was also
      elevated cerebrospinal fluid with high frequency hearing loss, suggesting that
      auditory cortex atrophies with high frequency hearing loss. These results
      indicate that Te1.0 is particularly affected by high frequency hearing loss and
      may be a target for evaluating the efficacy of interventions for hearing loss.

PMID- 22618354
TI  - Interpersonal violence among immigrants in Portugal.
AB  - To assess prevalence of interpersonal violence among a mixed gender sample of
      immigrants in Portugal, describing the type of violence and associated factors. A
      cross-sectional study was conducted between October 2008 and May 2009, evaluating
      a sample of 702 immigrants residing in the Lisbon region. Information was
      obtained by trained interviewers using a structured questionnaire. Overall, 15.1
      % (15.5 % females and 14.7 % males; p = 0.844) of the immigrants reported to be
      victims of at least one episode of violence during the last year, regardless of
      which type of violence was involved. The prevalence of intimate-partner violence
      was 4.1 %, and it was significantly higher among women than men (7.1 % vs. 0.9 %,
      respectively, p < 0.001). Women who reported being victims of violence during the
      previous year stated that the episodes occurred more often at home (54.4 %) with
      the partner as the perpetrator (43.9 %). On the other hand, male victims stated
      that the violent episodes occurred mostly in public spaces (40.8 %); men
      indicated that the perpetrator was frequently a stranger (28.6 %) or a co-worker
      (18.4 %). Violence is a frequent problem among both female and male immigrants
      living in Portugal, with different gender patterns regarding the perpetrators and
      settings of abuse.

PMID- 22618355
TI  - Does selective migration explain the Hispanic paradox? A comparative analysis of
      Mexicans in the U.S. and Mexico.
AB  - Latino immigrants, particularly Mexican, have some health advantages over U.S.
      born Mexicans and Whites. Because of their lower socioeconomic status, this
      phenomenon has been called the epidemiologic "Hispanic Paradox." While cultural
      theories have dominated explanations for the Paradox, the role of selective
      migration has been inadequately addressed. This study is among the few to combine
      Mexican and U.S. data to examine health selectivity in activity limitation, self
      rated health, and chronic conditions among Mexican immigrants, ages 18 and over.
      Drawing on theories of selective migration, this study tested the "healthy
      migrant" and "salmon-bias" hypotheses by comparing the health of Mexican
      immigrants in the U.S. to non-migrants in Mexico, and to return migrants in
      Mexico. Results suggest that there are both healthy migrant and salmon-bias
      effects in activity limitation, but not other health aspects. In fact, consistent
      with prior research, immigrants are negatively selected on self-rated health.
      Future research should consider the complexities of migrants' health profiles and
      examine selection mechanisms alongside other factors such as acculturation.

PMID- 22618356
TI  - Differences in the use of primary care services between Spanish national and
      immigrant patients.
AB  - Knowing what real use is made of health services by immigrant population is of
      great interest. The objectives are to analyze the use of primary care services by
      immigrants compared to Spanish nationals and to analyze these differences in
      relation to geographic origin. Retrospective observational study of all primary
      care visits made in 26 urban health centers. Main variable: total number of
      health centre visits/year. DEPENDENT VARIABLES: type of clinician requested; type
      of attention, and origin of immigrants. The independent variable was nationality.
      Statistics were obtained from the electronic medical records. The 4,933,521
      appointments made in 2007 were analyzed for a reference population of 594,145
      people (11.15% immigrants). The adjusted annual frequency for nationals was 8.3,
      versus whereas 4.6 for immigrants. The immigrant population makes less use of
      primary care services than national population. This is evident for all age
      groups and regardless of the immigrants' countries of origin. This result is
      important when planning health care resources for immigrant population.

PMID- 22618357
TI  - Association between parity and obesity in Mexican and Mexican-American women:
      findings from the Ella binational breast cancer study.
AB  - Obesity at diagnosis of breast cancer is associated with higher all-cause
      mortality and treatment-associated toxicities. We evaluated the association
      between parity and obesity in the Ella study, a population of Mexican and Mexican
      American breast cancer patients with high parity. Obesity outcomes included body
      mass index (BMI) >=30 kg/m(2), waist circumference (WC) >=35 in (88 cm), and
      waist-to-hip-ratio (WHR) >=0.85. Prevalence of obesity ([BMI] >= 30 kg/m(2)) was
      38.9 %. For WC, the multivariate odds ratio (OR) (95 % confidence interval [CI])
      for having WC >= 35 inches in women with >=4 pregnancies relative to those with 1
      2 pregnancies was 1.59 (1.01-2.47). Higher parity (>=4 pregnancies) was non
      significantly associated with high BMI (OR = 1.10; 95 % CI 0.73-1.67). No
      positive association was observed for WHR. Our results suggest WC is
      independently associated with high parity in Hispanic women and may be an optimal
      target for post-partum weight loss interventions.

PMID- 22618358
TI  - Non-adiabatic excited state dynamics of riboflavin after photoexcitation.
AB  - Flavins are chromophores in light-gated enzymes and therefore central in many
      photobiological processes. To unravel the optical excitation process as the
      initial, elementary step towards signal transduction, detailed ultrafast
      (femtosecond) experiments probing the photo-activation of flavins have been
      carried out recently [Weigel et al., J. Phys. Chem. B, 2011, 115, 3656-3680.].
      The present paper contributes to a further understanding and interpretation of
      these experiments by studying the post-excitation vibrational dynamics of
      riboflavin (RF) and microsolvated riboflavin, RF.4H2O, using first principles non
      adiabatic molecular dynamics. By analyzing the characteristic atom motions and
      calculating time-resolved stimulated emission spectra following pipi* excitation,
      it is found that after optical excitation C-N and C-C vibrations in the
      isoalloxazine rings of riboflavin set in. The Franck-Condon (vertically excited)
      state decays within about 10 fs, in agreement with experiment. Anharmonic
      coupling leads to Intramolecular Vibrational energy Redistribution (IVR) on the
      timescale of about 80-100 fs, first to (other) C-C stretching modes of the
      isoalloxazine rings, then by energy spread over the whole molecule, including low
      frequency in-plane modes. The IVR is accompanied by a red-shift and broadening of
      the emission spectrum. When RF is microsolvated with four water molecules, an
      overall redshift of optical spectra by about 20 nm is observed but the relaxation
      dynamics is only slightly affected. For several trajectories, a tendency for
      hydrogen transfer from water to flavin-nitrogen (N5) was found. 

PMID- 22618359
TI  - Edge removal in random contact networks and the basic reproduction number.
AB  - Understanding the effect of edge removal on the basic reproduction number R0 for
      disease spread on contact networks is important for disease management. The
      formula for the basic reproduction number R0 in random network SIR models of
      configuration type suggests that for degree distributions with large variance, a
      reduction of the average degree may actually increase R0. To understand this
      phenomenon, we develop a dynamical model for the evolution of the degree
      distribution under random edge removal, and show that truly random removal always
      reduces R0. The discrepancy implies that any increase in R0 must result from edge
      removal changing the network type, invalidating the use of the basic reproduction
      number formula for a random contact network. We further develop an epidemic model
      incorporating a contact network consisting of two groups of nodes with random
      intra- and inter-group connections, and derive its basic reproduction number. We
      then prove that random edge removal within either group, and between groups,
      always decreases the appropriately defined R0. Our models also allow an
      estimation of the number of edges that need to be removed in order to curtail an
      epidemic.

PMID- 22618360
TI  - Gamma knife radiosurgery of recurrent atypical neurocytoma. Case report and
      review of the literature.
AB  - BACKGROUND AND PURPOSE: The goal of this work was to demonstrate the efficacy of
      stereotactic gamma knife radiosurgery (GKRS) for the treatment of neurocytoma by
      means of a case report and a comprehensive literature review. CASE REPORT: A
      locally recurrent atypical neurocytoma in the area of the left third ventricle
      thalamic wall occurring 7 years after primary microsurgical resection in a 59
      year old woman was treated by GKRS. A marginal dose of 17 Gy was delivered to the
      surrounding 50% isodose. At the last follow-up, 82 months after radiosurgery, the
      tumor was locally controlled. For the literature review, computerized
      bibliographic searches of Pubmed were supplemented with hand searches of
      reference lists and abstracts of ASCO/ASTRO/ESTRO meetings. DISCUSSION: The
      present case confirms the results of the literature analysis. From 1997-2011, a
      total of 14 series were published providing results of GKRS in 86 patients (89
      lesions). The marginal doses, which have been applied, ranged from 9.6-20.0 Gy.
      With median follow-up intervals between 6 and 185 months, local control was 97.2%
      and local tumor progression of neurocytoma after GKRS was restricted to only 4
      cases. In accordance with our own experience, GKRS was not associated with a
      relevant early or late toxicity. CONCLUSION: GKRS can be assumed to be a safe and
      effective treatment modality of recurrent or residual neurocytoma.

PMID- 22618362
TI  - Cancer in Pacific people in New Zealand.
AB  - PURPOSE: To describe cancer incidence rates among Pacific people living in New
      Zealand from 1981 to 2004. METHODS: Linked census-cancer registration data were
      used to calculate age-standardized cancer incidence rates for Pacific people.
      Both trends over time within Pacific people and differences in rates between
      Pacific and European/Other people in New Zealand were assessed. RESULTS: Pacific
      rates were higher for cancers of the cervix, endometrium, gallbladder, lip, mouth
      and pharynx, liver, lung, ovary, pancreas, stomach, and thyroid, and lower for
      colorectal, bladder, and testicular cancers and melanoma. Differences were large,
      ranging from a 90 % lower rate of melanoma to over seven times higher rate of
      liver cancer compared to European/Other. Breast and prostate cancers were the
      commonest malignancies for Pacific women and men, respectively. Important changes
      for Pacific women over time include a 64 % decrease in cervical cancer incidence
      (ptrend = 0.02) and a 245 % increase for lung cancer (ptrend = 0.02), while men
      had a 366 % increase in prostate cancer (ptrend = 0.02). CONCLUSIONS: Pacific
      people in New Zealand have a disproportionate cancer burden related to infectious
      diseases such as HPV and Hepatitis B. However, with escalating evidence for
      causal associations between diabetes, obesity, and physical inactivity with
      various cancers, the challenge will be to prevent these cancers from rising in
      Pacific people who have the highest rates of these conditions in New Zealand.
      Disparities for tobacco-related cancers support tobacco consumption as another
      important cause of cancer incidence disparity. Continued efforts are needed to
      reduce infectious disease and improve screening program uptake among Pacific
      people.

PMID- 22618361
TI  - Adjuvant radiochemotherapy in patients with locally advanced high-risk cervical
      cancer.
AB  - BACKGROUND AND PURPOSE: The aim of this retrospective study was to analyze the
      outcome of patients with locally advanced cervical carcinoma treated by adjuvant
      radiochemotherapy and to determine risk factors for local and distant relapse.
      Furthermore, acute and late effects of treatment were recorded. PATIENTS AND
      METHODS: A total of 72 patients with FIGO stages I-III cervical carcinoma were
      treated by radical hysterectomy, pelvic lymphadenectomy, and postoperative
      radiochemotherapy. Only patients with positive pelvic lymph nodes, parametrial
      involvement, positive margins, or tumor bulk were eligible. Patients were
      irradiated with a standard pelvic field (50.4 Gy in 28 fractions). The majority
      of patients received platinum-based chemotherapy. RESULTS: After a median follow
      up of 37 months, estimated 1-, 2-, and 4-year disease-free survival (DFS) and
      overall survival (OS) rates were 89%, 80%, 68% and 95%, 88%, 76%, respectively.
      Nine of the 72 patients had pelvic recurrences including only 1 isolated local
      failure; 23 of the 72 patients presented with distant relapse. The majority of
      relapses occurred within the first 3 years after adjuvant treatment. The number
      of positive pelvic lymph nodes (> 1) was the strongest prognostic factor for DFS.
      Treatment was well tolerated with transient acute hematologic (~30%) and
      gastrointestinal (~30%) grade 3 toxicity. Small bowel obstruction (~6%) was the
      only important late sequelae. CONCLUSION: Adjuvant radiochemotherapy in patients
      with advanced cervical cancer and several risk factors is highly effective to
      prevent local relapse. Future efforts to improve outcome should be placed on
      improvement of systemic control especially in subgroups with high-risk features
      for distant relapse. Combined treatment was well tolerated with moderate acute
      and late toxicity.

PMID- 22618372
TI  - Actinotetraoses A-H: tetrasaccharide derivatives from a grasshopper-associated
      Amycolatopsis sp. HCa1.
AB  - Chemical investigation of the insect-derived actinomycete Amycolatopsis sp. HCa1
      with NMR-guided fractionation led to the isolation of eight new tetrasaccharide
      derivatives containing an unusual nonreducing glucotetraose skeleton, named
      actinotetraoses A-H (1-8), and one known compound, tigloside (9). The structures
      of these compounds were determined on the basis of analyses of their
      spectroscopic data. The in vitro immunosuppressive activity and cytotoxicity of
      these compounds were evaluated by T cell viability and MTT assays, respectively.
      Only actinotetraose E (5) displayed weak immunosuppressive activity.

PMID- 22618373
TI  - Geranyl flavonoid derivatives from the fresh leaves of Artocarpus communis and
      their anti-inflammatory activity.
AB  - Breadfruit (Artocarpus communis) is a widely distributed crop in tropical and
      subtropical regions of the world. It is used in Southeast Asia and India to treat
      several inflammatory disorders. The aim of this study was to investigate the
      presence of anti-inflammatory flavonoids in A. communis leaves. Three new geranyl
      flavonoids, arcommunol C (1), arcommunol D (3), and 5'-geranyl-3,4,2',4'
      tetrahydroxychalcone (5), together with four known compounds, prostratol (2),
      arcommunol E (4), 3'-geranyl-3,4,2',4'-tetrahydroxydihydrochalcone (6), and 3'
      geranyl-3,4,2',4'-tetrahydroxychalcone (7), were isolated from the leaves of A.
      communis. Compound 4 was isolated for the first time from natural sources. The
      anti-inflammatory activity of the isolated compounds (1-7) was evaluated by
      determining their inhibitory activity on the production of proinflammatory
      mediators in lipopolysaccharide (LPS)-activated RAW 264.7 murine macrophage
      cells. Compounds 2, 3, and 4 suppressed the LPS-induced production of nitric
      oxide (NO) in RAW 264.7 cells with IC50 values of 8.13 +/- 0.17, 18.45 +/- 2.15,
      and 22.74 +/- 1.74 uM, respectively. Furthermore, 2 decreased lipopolysaccharide
      (LPS)-mediated induction of protein expressions of inducible nitric oxide
      synthase (iNOS) and cyclooxygenase-2 (COX-2) in RAW 264.7 cells. It was also
      found that 2 suppressed LPS-induced phosphorylation of JNK and p38 mitogen
      activated protein kinase (MAPK) signaling.

PMID- 22618374
TI  - Regulation of medicinal plants for public health--European community monographs
      on herbal substances.
AB  - The European legislation on medicinal products also addresses the medicinal use
      of products originating from plants. The objective of the legislation is to
      ensure the future existence of such products and to consider particular
      characteristics when assessing quality, efficacy, and safety. Two categories are
      defined: i) herbal medicinal products can be granted a marketing authorisation;
      and ii) traditional herbal medicinal products can be granted a registration based
      on their longstanding use if they are complying with a set of provisions ensuring
      their safe use. The Committee on Herbal Medicinal Products (HMPC) was established
      at the European Medicines Agency (EMA) to provide monographs and list entries on
      herbal substances and preparations thereof. Meanwhile, approx. 100 monographs
      have been published, which define a current scientific and regulatory standard
      for efficacy and safety of herbal substances and herbal preparations used in
      medicinal products. This harmonised European standard will facilitate the
      availability and adequate use of traditional herbal medicinal products and herbal
      medicinal products within the European Union. Consequent labelling shall also
      enable patients and health care professionals to differentiate medicinal products
      from other product categories like cosmetics, food supplements, and medical
      devices.

PMID- 22618376
TI  - Theoretical investigations on structure, density, detonation properties, and
      sensitivity of the derivatives of PYX.
AB  - The -NH(2), -NO(2), -N(3), -NHNO(2), and -ONO(2) substitution derivatives of PYX
      (2,6-bis(picrylamino)-3,5-dinitropyridine) were studied at the B3LYP/6-31G**
      level of density functional theory. The sublimation enthalpies and heats of
      formation (HOFs) in gas phase and solid state of these compounds were calculated.
      The theoretical predicted density (rho), detonation pressure (P), and detonation
      velocity (D) showed that these derivatives have better detonation performance
      than PYX. The effects of substituent groups on HOF, rho, P, and D were discussed.
      The order of contribution of various groups to P and D was -ONO(2) > -NO(2) > 
      NHNO(2) > -N(3) > -NH(2). Sensitivity was evaluated using the frontier orbital
      energies, bond orders, bond dissociation enthalpies (BDEs), and characteristic
      heights (h(50)). The trigger bonds in the pyrolysis process for these PYX
      derivatives may be Ring-NO(2), NH-NO(2), or O-NO(2) varying with the
      substituents. The h(50) of most compounds are larger than that of CL-20, and
      those of -NH(2), -NO(2), and most -ONO(2) derivatives are larger than that of
      RDX. The BDEs of the trigger bonds of all but the -ONO(2) derivatives are
      sufficiently large. Taking both detonation performance and sensitivity into
      consideration, some derivatives of PYX may be good candidates of explosives.

PMID- 22618377
TI  - New advances in imaging osteoporosis and its complications.
AB  - Tremendous advances have been made over the past several decades in assessing
      osteoporosis and its complications. High resolution imaging combined with
      sophisticated computational techniques now provide a detailed analysis of bone
      structure and a much more accurate prediction of bone strength. These techniques
      have shown how different mechanisms of age-related bone weakening exist in males
      and females. Limitations peculiar to these more advanced imaging techniques
      currently hinder their adoption into mainstream clinical practice. As such, the
      ultimate quest remains a readily available, safe, high resolution technique
      capable of fully predicting bone strength, capable of showing how bone strength
      is faltering and precisely monitoring treatment effect. Whether this technique
      will be based on acquisition of spine/hip data or data obtained at peripheral
      sites reflective of changes happening in the spine and hip regions is still not
      clear. In the meantime, mainstream imaging will continue to improve the detection
      of osteoporosis related insufficiency fracture in the clinical setting. We, as
      clinicians, should aim to increase awareness of this fracture type both as a
      frequent and varied source of pain in patients with osteoporosis and as the
      ultimate marker of severely impaired bone strength.

PMID- 22618378
TI  - Parathyroid incidentalomas detected during thyroid ultrasonography and effect of
      chronic thyroiditis on false positive parathyroid lesions.
AB  - We aimed to determine the prevalence of parathyroid incidentalomas in patients
      referred for thyroid ultrasonography (US) and investigate the role of chronic
      thyroiditis on false positive lesions. Patients suspected to have parathyroid
      lesions during thyroid US were recorded prospectively between August 2009 and
      January 2010. Patients referred for parathyroid US and patients with known high
      serum calcium or parathyroid hormone (PTH) levels were excluded. Suspected
      parathyroid lesions were defined as hypoechoic, homogeneous, solid lesions with
      regular margins located outside the thyroid lobe, most commonly inferior to the
      thyroid gland. Thyroid US was performed in 6,528 patients. There were 78 patients
      (1.19 %) (73 female and 5 male) with suspected parathyroid lesion. The diagnosis
      of a true parathyroid adenoma was confirmed in 6 (7.69 %) patients. In patients
      with true adenoma, mean serum calcium, phosphorus, and PTH levels were 10.57 +/-
      0.48 mg/dl, 3.03 +/- 0.52 mg/dl, and 182.91 +/- 46.62 pg/ml, respectively. Among
      72 patients with false positive parathyroid lesion, antithyroid peroxidase
      antibody was positive in 50 (69.4 %), antithyroglobulin antibody was positive in
      46 (63.9 %), and one of these antibodies were positive in 59 (81.9 %) patients.
      Also, 46 (63.9 %) of these patients had thyroid dysfunctions (43 hypothyroidism
      and 3 hyperthyroidism) and 59 (81.9 %) had chronic thyroiditis
      ultrasonographically. Parathyroid incidentaloma was detected in 0.09 % of
      patients referred for thyroid US. The presence of clinically or
      ultrasonographically chronic thyroiditis might cause inadvertent interpretation
      of a hypoechoic lesion as a parathyroid pathology during thyroid US.

PMID- 22618379
TI  - Which risk factors are more associated with ischemic stroke than intracerebral
      hemorrhage in patients with atrial fibrillation?
AB  - BACKGROUND AND PURPOSE: The decision to prescribe oral anticoagulant therapy in
      patients with atrial fibrillation is based on an assessment of the competing
      risks of ischemic stroke and major bleeding, of which intracerebral hemorrhage
      (ICH) is the most important type. We sought to determine the comparative
      importance of risk factors for ischemic stroke and ICH in patients with acute
      stroke and atrial fibrillation with particular emphasis on risk factors common to
      both stroke types. METHODS: Consecutive patients with acute ischemic stroke or
      ICH and atrial fibrillation included in the Registry of the Canadian Stroke
      Network constituted the cohort. Multivariable logistic regression analysis was
      used to determine the association between baseline risk factors and presentation
      with ICH versus ischemic stroke. Risk factors included: (1) those previously
      reported to be risk factors for both ischemic stroke and major bleeding
      (particularly ICH) ("shared" risk factors, including age, alcohol, hypertension,
      diabetes mellitus, renal impairment, prior stroke/transient ischemic attack and
      preadmission dementia); and (2) other risk factors associated with either stroke
      subtype alone. RESULTS: A total of 3197 patients presented with atrial
      fibrillation and acute stroke, of which 12.2% presented with ICH. Of the "shared"
      risk factors, age (OR, 1.19; 95% CI, 1.06-1.34 per decade) and prior
      stroke/transient ischemic attack (OR, 1.45; 95% CI, 1.12-1.87) were more
      associated with ischemic stroke than ICH, whereas a history of hypertension (OR,
      0.89; 95% CI, 0.68-1.17), diabetes mellitus (OR 1.23; 95% CI, 0.92-1.64), renal
      impairment (OR, 1.28; 95% CI, 0.95-1.71), and alcohol intake were not more
      strongly associated with either stroke subtype. CONCLUSION: Of the risk factors
      known to be associated with both ischemic stroke and ICH in patients with atrial
      fibrillation, we found that none had a stronger association with ICH. Older age
      was more strongly associated with ischemic stroke than ICH.

PMID- 22618380
TI  - Posttraumatic stress disorder and adherence to medications in survivors of
      strokes and transient ischemic attacks.
AB  - BACKGROUND AND PURPOSE: Posttraumatic stress disorder (PTSD) can be triggered by
      life-threatening medical events such as strokes and transient ischemic attacks
      (TIAs). Little is known regarding how PTSD triggered by medical events affects
      patients' adherence to medications. METHODS: We surveyed 535 participants, age
      >=40 years old, who had at least 1 stroke or TIA in the previous 5 years. PTSD
      was assessed using the PTSD Checklist-Specific for stroke; a score >=50 on this
      scale is highly specific for PTSD diagnosis. Medication adherence was measured
      using the 8-item Morisky scale. Logistic regression was used to test whether PTSD
      after stroke/TIA was associated with increased risk of medication nonadherence.
      Covariates for adjusted analyses included sociodemographics, Charlson comorbidity
      index, modified Rankin Scale score, years since last stroke/TIA, and depression.
      RESULTS: Eighteen percent of participants had likely PTSD (PTSD Checklist
      Specific for stroke >=50), and 41% were nonadherent to medications according to
      the Morisky scale. A greater proportion of participants with likely PTSD were
      nonadherent to medications than other participants (67% versus 35%, P<0.001). In
      the adjusted model, participants with likely PTSD were nearly 3 times more likely
      (relative risk, 2.7; 95% CI, 1.7-4.2) to be nonadherent compared with
      participants without PTSD (PTSD Checklist-Specific for stroke <25) even after
      controlling for depression, and there was a graded association between PTSD
      severity and medication nonadherence. CONCLUSION: PTSD is common after
      stroke/TIA. Patients who have PTSD after stroke or TIA are at increased risk for
      medication nonadherence.

PMID- 22618381
TI  - Modulation of training by single-session transcranial direct current stimulation
      to the intact motor cortex enhances motor skill acquisition of the paretic hand.
AB  - BACKGROUND AND PURPOSE: Mechanisms of skill learning are paramount components for
      stroke recovery. Recent noninvasive brain stimulation studies demonstrated that
      decreasing activity in the contralesional motor cortex might be beneficial,
      providing transient functional improvements after stroke. The more crucial
      question, however, is whether this intervention can also enhance the acquisition
      of complex motor tasks, yielding longer-lasting functional improvements. In the
      present study, we tested the capacity of cathodal transcranial direct current
      stimulation (tDCS) applied over the contralesional motor cortex during training
      to enhance the acquisition and retention of complex sequential finger movements
      of the paretic hand. METHOD: Twelve well-recovered chronic patients with
      subcortical stroke attended 2 training sessions during which either cathodal tDCS
      or a sham intervention were applied to the contralesional motor cortex in a
      double-blind, crossover design. Two different motor sequences, matched for their
      degree of complexity, were tested in a counterbalanced order during as well as 90
      minutes and 24 hours after the intervention. Potential underlying mechanisms were
      evaluated with transcranial magnetic stimulation. RESULTS: tDCS facilitated the
      acquisition of a new motor skill compared with sham stimulation (P=0.04) yielding
      better task retention results. A significant correlation was observed between the
      tDCS-induced improvement during training and the tDCS-induced changes of
      intracortical inhibition (R(2)=0.63). CONCLUSIONS: These results indicate that
      tDCS is a promising tool to improve not only motor behavior, but also procedural
      learning. They further underline the potential of noninvasive brain stimulation
      as an adjuvant treatment for long-term recovery, at least in patients with mild
      functional impairment after stroke.

PMID- 22618382
TI  - Angiogenesis: a harmonized target for recovery after stroke.

PMID- 22618383
TI  - Axonal outgrowth and dendritic plasticity in the cortical peri-infarct area after
      experimental stroke.
AB  - BACKGROUND AND PURPOSE: Axonal remodeling is critical to brain repair after
      stroke. The present study investigated axonal outgrowth after stroke and the
      signaling pathways mediating axonal outgrowth in cortical neurons. METHODS: Using
      a rodent model of middle cerebral artery occlusion, we examined high-molecular
      weight neurofilament (NFH) immunoreactive axons and myelin basic protein-positive
      oligodendrocytes in the peri-infarct area. In vitro, using cultured cortical
      neurons in a microfluidic chamber challenged by oxygen-glucose deprivation (OGD),
      we investigated mechanisms selectively regulating axonal outgrowth after OGD.
      RESULTS: NFH(+) axons and MBP(+) oligodendrocytes substantially increased in the
      peri-infarct area during stroke recovery, concomitantly with an increase in
      dendrites and spines identified by Golgi-Cox staining. In vitro, cortical neurons
      subjected to OGD exhibited significant increases in axonal outgrowth and in
      phosphorylated NFH protein levels, concurrently with downregulation of
      phosphatase tensin homolog deleted on chromosome 10, activation of Akt, and
      inactivation of glycogen synthase kinase-3beta in regenerated axons. Blockage of
      phosphoinositide 3-kinase with pharmacological inhibitors suppressed Akt
      activation and attenuated phosphorylation of glycogen synthase kinase-3beta,
      which resulted in suppression of phosphorylated NFH and axonal outgrowth after
      OGD; whereas GSK-3 inhibitors augmented axonal regeneration and elevated
      phosphorylated NFH levels after OGD. CONCLUSIONS: Stroke induces axonal outgrowth
      and myelination in rodent ischemic brain during stroke recovery, and the
      phosphoinositide 3-kinase/Akt/glycogen synthase kinase-3beta signaling pathway
      mediates axonal regeneration of cortical neurons after OGD.

PMID- 22618384
TI  - Clinical significance of impaired cerebrovascular autoregulation after severe
      aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to investigate the
      relationship between cerebrovascular autoregulation and outcome after aneurysmal
      subarachnoid hemorrhage. METHODS: In a prospective observational study, 80
      patients after severe subarachnoid hemorrhage were continuously monitored for
      cerebral perfusion pressure and partial pressure of brain tissue oxygen for an
      average of 7.9 days (range, 1.9-14.9 days). Autoregulation was assessed using the
      index of brain tissue oxygen pressure reactivity (ORx), a moving correlation
      coefficient between cerebral perfusion pressure and partial pressure of brain
      tissue oxygen. High ORx indicates impaired autoregulation; low ORx signifies
      intact autoregulation. Outcome was determined at 6 months and dichotomized into
      favorable (Glasgow Outcome Scale 4-5) and unfavorable outcome (Glasgow Outcome
      Scale 1-3). RESULTS: Twenty-four patients had a favorable and 56 an unfavorable
      outcome. In a univariate analysis, there were significant differences in
      autoregulation (ORx 0.19+/-0.10 versus 0.37+/-0.11, P<0.001, for favorable versus
      unfavorable outcome, respectively), age (44.1+/-11.0 years versus 54.2+/-12.1
      years, P=0.001), occurrence of delayed cerebral infarction (8% versus 46%,
      P<0.001), use of coiling (25% versus 54%, P=0.02), partial pressure of brain
      tissue oxygen (24.9+/-6.6 mm Hg versus 21.8+/-6.3 mm Hg, P=0.048), and Fisher
      grade (P=0.03). In a multivariate analysis, ORx (P<0.001) and age (P=0.003)
      retained an independent predictive value for outcome. ORx correlated with Glasgow
      Outcome Scale (r=-0.70, P<0.001). CONCLUSIONS: The status of cerebrovascular
      autoregulation might be an important pathophysiological factor in the disease
      process after subarachnoid hemorrhage, because impaired autoregulation was
      independently associated with an unfavorable outcome.

PMID- 22618385
TI  - Letter by Freeman et al regarding article, "Intracranial hemorrhage in atrial
      fibrillation patients during anticoagulation with warfarin or dabigatran: the RE
      LY Trial".

PMID- 22618408
TI  - Integrated restoration of small watershed in Karst regions of southwest China.

PMID- 22618409
TI  - Borderline metal-catalyzed carboarylation of alkynylarenes using N,O-acetals.
AB  - Borderline metal catalysts, Bi(OTf)(3) and Fe(OTf)(3), were proven to work as
      dual activators for alkynes and N,O-acetals via sigma,pi-chelation, which
      achieved a new carboarylation reaction of alkynylarenes with N,O-acetals.

PMID- 22618410
TI  - Combined toxicity of three chlorophenols 2,4-dichlorophenol, 2,4,6
      trichlorophenol and pentachlorophenol to Daphnia magna.
AB  - The toxicity of single and combined mixtures of 2,4-dichlorophenol (2,4-DCP),
      2,4,6-trichlorophenol (2,4,6-TCP), and pentachlorophenol (PCP) to Daphnia magna
      was studied. The toxicity ranking of these three single chlorophenols (CPs) to
      Daphnia magna was PCP > 2,4-DCP > 2,4,6-TCP. The toxic units (TU) approach was
      used to estimate the combined effects in experiments, the median effective
      concentration (EC(50)) values were 0.87-1.21 and 0.46-0.59 for binary and ternary
      mixtures, respectively. Response surface models of General Linear Models (R(2) >
      0.90, residual deviation < 3.25) were established for all three binary mixtures.
      The toxicity for ternary mixtures based on the EC(50)-value and 10% effective
      concentration (EC(10))-value fixed mixture ratio presented a synergism. The risk
      based on the single CP's toxicity test may be underestimated. In addition, four
      approaches (concentration addition, toxicity equivalency factors, effect
      summation, and independent action) were used for the calculation of combined
      effects of the mixture. The experimental results showed that concentration
      addition and toxicity equivalency factor approaches were effective methods for
      calculation of additive effects of mixtures from binary systems of CPs; while
      independent action and effect summation (low simulated tail) predicted lower
      toxicity than experimental results. Limitations of the traditional focus on the
      effects of single agents were highlighted; hazard assessments ignoring the
      possibility of joint action of CPs will almost certainly lead to significant
      underestimations of risk.

PMID- 22618411
TI  - Major depressive disorder in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the point prevalence of major depressive disorder (MDD)
      as diagnosed by the Mini-International Neuropsychiatric Interview (M.I.N.I) in
      patients with rheumatoid arthritis (RA) and to determine whether MDD is related
      to features of RA disease, such as disease activity or physical dysfunction.
      METHODS: Of the patients with RA who participated in the IORRA survey conducted
      in October 2005, 162 were evaluated using the M.I.N.I., the Center for
      Epidemiologic Studies-Depression (CES-D) scale, and the two-question depression
      screen for MDD. RA clinical features were obtained from the concomitant IORRA
      cohort database. Relationships between MDD and RA disease features were analyzed
      by the Wilcoxon rank sum test and Pearson's chi-square test. RESULTS: The point
      prevalence of MDD as diagnosed by the M.I.N.I. was 6.8 % in our Japanese patients
      with RA. The percentage of depressive patients was determined to be 23.5, 17.3,
      or 7.4 % according to the CES-D scale with cut-off points of 16, 19, or 27,
      respectively, and 14.2 % according to the two-question depression screen. The
      best cut-off point for CES-D for risk of MDD diagnosed by M.I.N.I. in this study
      was determined to be 23, with 11.7 % depressive patients having the highest sum
      of sensitivity and specificity. No relationship between MDD and RA disease
      activity was detected. CONCLUSION: By using the well-established structural
      interview instrument M.I.N.I., we determined the point prevalence of MDD in the
      RA patients enrolled in this study to be 6.8 %, leading to the conclusion that
      concomitant MDD does not seem to influence disease activity in RA patients.

PMID- 22618412
TI  - Dimensions of religiousness and cancer screening behaviors among church-going
      Latinas.
AB  - Churches are a promising setting through which to reach Latinas with cancer
      control efforts. A better understanding of the dimensions of religiousness that
      impact health behaviors could inform efforts to tailor cancer control programs
      for this setting. The purpose of this study was to explore relationships between
      dimensions of religiousness with adherence to cancer screening recommendations
      among church-going Latinas. Female Spanish-speaking members, aged 18 and older
      from a Baptist church in Boston, Massachusetts (N = 78), were interviewed about
      cancer screening behaviors and dimensions of religiousness. We examined adherence
      to individual cancer screening tests (mammography, Pap test, and colonoscopy), as
      well as adherence to all screening tests for which participants were age
      eligible. Dimensions of religiousness assessed included church participation,
      religious support, active and passive spiritual health locus of control, and
      positive and negative religious coping. Results showed that roughly half (46 %)
      of the sample had not received all of the cancer screening tests for which they
      were age-eligible. In multivariate analyses, positive religious coping was
      significantly associated with adherence to all age-appropriate screening (OR =
      5.30, p < .01). Additional research is warranted to replicate these results in
      larger, more representative samples and to examine the extent to which
      enhancement of religious coping could increase the impact of cancer control
      interventions for Latinas. 

PMID- 22618413
TI  - Relationships among spirituality, religious practices, personality factors, and
      health for five different faith traditions.
AB  - To determine: (1) differences in spirituality, religiosity, personality, and
      health for different faith traditions; and (2) the relative degree to which
      demographic, spiritual, religious, and personality variables simultaneously
      predict health outcomes for different faith traditions. Cross-sectional analysis
      of 160 individuals from five different faith traditions including Buddhists (40),
      Catholics (41), Jews (22), Muslims (26), and Protestants (31). Brief
      multidimensional measure of religiousness/spirituality (BMMRS; Fetzer in
      Multidimensional measurement of religiousness/spirituality for use in health
      research, Fetzer Institute, Kalamazoo, 1999); NEO-five factor inventory (NEO-FFI;
      in Revised NEO personality inventory (NEO PI-R) and the NEO-five factor inventory
      (NEO-FFI) professional manual, Psychological Assessment Resources, Odessa, Costa
      and McCrae 1992); Medical outcomes scale-short form (SF-36; in SF-36 physical and
      mental health summary scores: A user's manual, The Health Institute, New England
      Medical Center, Boston, Ware et al. 1994). (1) ANOVAs indicated that there were
      no significant group differences in health status, but that there were group
      differences in spirituality and religiosity. (2) Pearson's correlations for the
      entire sample indicated that better mental health is significantly related to
      increased spirituality, increased positive personality traits (i.e.,
      extraversion) and decreased personality traits (i.e., neuroticism and
      conscientiousness). In addition, spirituality is positively correlated with
      positive personality traits (i.e., extraversion) and negatively with negative
      personality traits (i.e., neuroticism). (3) Hierarchical regressions indicated
      that personality predicted a greater proportion of unique variance in health
      outcomes than spiritual variables. Different faith traditions have similar health
      status, but differ in terms of spiritual, religious, and personality factors. For
      all faith traditions, the presence of positive and absence of negative
      personality traits are primary predictors of positive health (and primarily
      mental health). Spiritual variables, other than forgiveness, add little to the
      prediction of unique variance in physical or mental health after considering
      personality. Spirituality can be conceptualized as a characterological aspect of
      personality or a distinct construct, but spiritual interventions should continue
      to be used in clinical practice and investigated in health research.

PMID- 22618414
TI  - Exploiting a novel size exclusion phenomenon for enantioselective acid/base
      cascade catalysis.
AB  - A novel size exclusion phenomenon between PS-BEMP and sterically bulky BPAs, has
      been discovered and exploited in a one-pot base-catalysed Michael addition/acid
      catalysed enantioselective N-acyliminium cyclisation cascade, allowing the
      preparation of structurally complex beta-carbolines with moderate to good
      enantiocontrol.

PMID- 22618432
TI  - Selective recognition induced nanostructures in a cucurbit[7]uril-based host
      guest system: micelles, nanorods and nanosheets.
AB  - The selective recognition between CB[7] and hexadecyl dimethyl benzyl ammonium
      chloride (HDBAC) was investigated using ITC and NMR. The long alkyl-bearing
      surfactant can form micelles when dispersed in water. We found that progressive
      addition of CB[7] into the HDBAC dispersion induced the transformation of
      micelles into various self-organized structures including nanorods and nanosheets
      as evidenced by DLS, TEM, AFM and SAXS. A rational mechanism is proposed to
      illustrate the host-guest interaction induced transformation process. 

PMID- 22618433
TI  - Automatic stent strut detection in intravascular optical coherence tomographic
      pullback runs.
AB  - We developed and evaluated an automatic stent strut detection method in
      intravascular optical coherence tomography (IVOCT) pullback runs. Providing very
      high resolution images, IVOCT has been rapidly accepted as a coronary imaging
      modality for the optimization of the stenting procedure and its follow-up
      evaluation based on stent strut analysis. However, given the large number of
      struts visible in a pullback run, quantitative three-dimensional analysis is only
      feasible when the strut detection is performed automatically. The presented
      method first detects the candidate pixels using both a global intensity histogram
      and the intensity profile of each A-line. Gaussian smoothing is applied followed
      by specified Prewitt compass filters to detect the trailing shadow of each strut.
      Next, the candidate pixels are clustered using the shadow information. In the
      final step, several filters are applied to remove the false positives such as the
      guide wire. Our new method requires neither a priori knowledge of the strut
      status nor the lumen/vessel contours. In total, 10 IVOCT pullback runs from a 1
      year follow-up study were used for validation purposes. 18,311 struts were
      divided into three strut status categories (malapposition, apposition or covered)
      and classified based on the image quality (high, medium or low). The inter
      observer agreement is 95%. The sensitivity was defined as the ratio of the number
      of true positives and the total number of struts in the expert defined result.
      The proposed approach demonstrated an average sensitivity of 94%. For malapposed,
      apposed and covered stent struts, the sensitivity of the method is respectively
      91, 93 and 94%, which shows the robustness towards different situations. The
      presented method can detect struts automatically regardless of the strut status
      or the image quality, and thus can be used for quantitative measurement, 3D
      reconstruction and visualization of the stents in IVOCT pullback runs.

PMID- 22618434
TI  - Contrast media volume optimization in high-pitch dual-source CT coronary
      angiography: feasibility study.
AB  - To investigate the feasibility of contrast media (CM) volume reduction in dual
      source coronary computed tomography angiography high-pitch mode without affecting
      coronary artery enhancement. Eighty patients were involved in a preliminary
      experiment with a default injection protocol (60 ml of CM). The age, BMI, test
      bolus (TB) enhancement peak and the CT values of coronary artery for each patient
      were recorded and the key factors for determining coronary artery enhancement
      were investigated. Based on the results of the preliminary experiment, 120
      patients were involved in the main experiment with a new injection protocol. For
      each patient, the CT values and noise of left coronary sinus (LCS), and the
      distal segment of right coronary artery were measured. In the preliminary
      experiment, the peak enhancement of TB correlated most strongly with the HU
      values of coronary artery. Consequently, the new injection protocol was devised
      to catalog patients into four groups (30, 40, 50 and 60 ml) of CM based on their
      TB peak enhancement. In the main experiment, the 30 ml CM injection group whose
      peak attenuation of TB were the highest (30 vs. 40,50,60 ml: 323.0 +/- 27.5 vs.
      264.2 +/- 11.9, 242.1 +/- 8.8, 206.2 +/- 18.2 HU, p < 0.05), obtained the highest
      attenuation of LCS (30 vs. 40,50,60 ml: 365.0 +/- 41.2 vs. 341.8 +/- 40.0, 326.9
      +/- 34.7, 312.5 +/- 38.2 HU p < 0.05). Contrast optimization is feasible in high
      pitch DSCT coronary angiography. Certain patients may receive 30 ml of CM without
      affecting vessel enhancement.

PMID- 22618435
TI  - Triple rule-out acute chest pain evaluation using a 320-row-detector volume CT: a
      comparison of the wide-volume and helical modes.
AB  - The purpose of this study was to investigate the image quality and radiation dose
      of triple rule-out computed tomography (TROCT) using a 320-row-detector volume CT
      system to compare the wide-volume and helical modes of this CT system. Sixty-four
      patients with noncritical chest pain were allocated to one of 2 groups according
      to the type of CT examination mode used. Group 1 patients were examined using the
      wide-volume (non-spiral) mode and group 2 patients were examined using the 160
      detector row helical mode, with the same contrast injection protocol in both
      methods [biphasic injection protocol; injection rate of 4 ml/s, median volume, 70
      ml (range 65-100 ml)]. Attenuations of the pulmonary trunk, ascending aorta, and
      coronary arteries were measured in Hounsfield units; a subjective overall patient
      based image quality score of 1-3 was awarded to each study. Effective doses,
      signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated.
      Average effective dose was significantly lower in group 1 than group 2 (9.7 +/-
      5.1 vs. 16 +/- 5.9 mSv, P < 0.001). The mean attenuation of the main pulmonary
      trunk was significantly higher in group 1 than group 2 (P = 0.04) and mean
      attenuations in other vessels were not significant different. SNR and CNR were
      not significantly different between the groups. The proportion of diagnostic
      image qualities for chest CT angiography (CTA) was similar between the groups
      (93.5 vs. 93.9 %). In coronary CTA, group 1 showed a higher proportion of
      diagnostic image qualities than group 2 (100 vs. 87.9 %). The use of wide-volume
      mode of 320-detector CT reduces the overall effective radiation dose and results
      in similar attenuation and image quality for TROCT as compared with the helical
      mode.

PMID- 22618436
TI  - A TRP5/5-fluoroanthranilic acid counter-selection system for gene disruption in
      Candida guilliermondii.
AB  - Candida guilliermondii is an interesting biotechnological model for the
      industrial production of value-added metabolites and also remains an
      opportunistic emerging fungal agent of candidiasis often associated with oncology
      patients. The aim of the present study was to establish a convenient
      transformation system for C. guilliermondii by developing both an ATCC 6260
      derived recipient strain and a recyclable selection marker. We first disrupted
      the TRP5 gene in the wild-type strain and demonstrated that trp5 mutants were
      tryptophan auxotroph as well as being resistant to the antimetabolite 5
      fluoroanthranilic acid (FAA). Following an FAA selection of spontaneous mutants
      derived from the ATCC 6260 strain and complementation analysis, we demonstrated
      that trp5 genotypes could be directly recovered on FAA-containing medium. The
      TRP5 wild-type allele, flanked by two short repeated sequences of its 3'UTR, was
      then used to disrupt the FCY1 gene in C. guilliermondii trp5 recipient strains.
      The resulting fcy1 mutants displayed strong flucytosine resistance and a counter
      selection on FAA allowed us to pop-out the TRP5 allele from the FCY1 locus. To
      illustrate the capacity of this blaster system to achieve a second round of gene
      disruption, we knocked out both the LEU2 and the HOG1 genes in the trp5, fcy1
      background. Although all previously described yeast "TRP blaster" disruption
      systems used TRP1 as counter-selectable marker, this study demonstrated the
      potential of the TRP5 gene in such strategies. This newly created "TRP5 blaster"
      disruption system thus represents a powerful genetic tool to study the function
      of a large pallet of genes in C. guilliermondii.

PMID- 22618437
TI  - Characterisation of cannabinoid 1 receptor expression in the perikarya, and
      peripheral and spinal processes of primary sensory neurons.
AB  - The cannabinoid 1 (CB1) receptor is expressed by a sub-population of primary
      sensory neurons. However, data on the neurochemical identity of the CB1 receptor
      expressing cells, and CB1 receptor expression by the peripheral and central
      terminals of these neurons are inconsistent and limited. We characterised CB1
      receptor expression in dorsal root ganglia (DRG) and spinal cord at the lumbar 4
      5 level, as well as in the urinary bladder and glabrous skin of the hindpaw.
      About 1/3 of DRG neurons exhibited immunopositivity for the CB1 receptor, the
      majority of which showed positivity for the nociceptive markers calcitonin gene
      related peptide (CGRP) or/and Griffonia (bandeiraea) simplicifolia IB4 isolectin
      binding. Virtually all CB1 receptor-immunostained fibres showed immunopositivity
      for CGRP in the skin, while very few did in the urinary bladder. No CB1 receptor
      immunopositive nerve fibres were IB4 positive in either peripheral tissue. Spinal
      laminae I and II-outer showed the highest density of CB1 receptor-immunopositive
      punctae, the majority of which showed positivity for CGRP or/and IB4 binding.
      These data indicate that a major sub-population of nociceptive primary sensory
      neurons expresses CB1 receptors that are transported to both peripheral and
      central terminals of these cells. Therefore, the present data suggest that
      manipulation of endogenous CB1 receptor agonist levels in these areas may
      significantly reduce nociceptive input into the spinal cord.

PMID- 22618438
TI  - Altered diffusion tensor imaging measurements in aged transgenic Huntington
      disease rats.
AB  - Rodent models of Huntington disease (HD) are valuable tools for investigating HD
      pathophysiology and evaluating new therapeutic approaches. Non-invasive
      characterization of HD-related phenotype changes is important for monitoring
      progression of pathological processes and possible effects of interventions. The
      first transgenic rat model for HD exhibits progressive late-onset affective,
      cognitive, and motor impairments, as well as neuropathological features
      reflecting observations from HD patients. In this report, we contribute to the
      anatomical phenotyping of this model by comparing high-resolution ex vivo DTI
      measurements obtained in aged transgenic HD rats and wild-type controls. By
      region of interest analysis supplemented by voxel-based statistics, we find
      little evidence of atrophy in basal ganglia regions, but demonstrate altered DTI
      measurements in the dorsal and ventral striatum, globus pallidus, entopeduncular
      nucleus, substantia nigra, and hippocampus. These changes are largely compatible
      with DTI findings in preclinical and clinical HD patients. We confirm earlier
      reports that HD rats express a moderate neuropathological phenotype, and provide
      evidence of altered DTI measures in specific HD-related brain regions, in the
      absence of pronounced morphometric changes.

PMID- 22618456
TI  - Hepatocyte transporter expression in FNH and FNH-like nodule: correlation with
      signal intensity on gadoxetic acid enhanced magnetic resonance images.
AB  - PURPOSE: Our aim was to evaluate the hepatocyte transporters in focal nodular
      hyperplasia (FNH) and FNH-like lesions and to correlate the grade of its
      expression with signal intensity on the hepatobiliary phase (HB phase) of
      gadoxetic-acid-enhanced magnetic resonance imaging (EOB-MRI). MATERIALS AND
      METHODS: Thirteen histopathological confirmed cases including eight with EOB-MRI
      were studied. Immunohistochemical staining for transporter was performed and its
      grade semiquantitatively analyzed. RESULTS: Histopathologically, ten cases showed
      almost equal organic anion transporter polypeptide (OATP) 8 expression relative
      to the surrounding liver; the remaining three showed stronger OATP8 expression.
      In eight cases with EOB-MRI, two demonstrated more hyperintensity on the HB
      phase, and their OATP8 expression was stronger compared with the surrounding
      liver. The remaining six cases showed isointensity on the HB phase and revealed
      almost equal OATP8 expression. The expression of export transporter multi-drug
      resistant proteins (MRP) 1 and 2 were almost equal relative to the surrounding
      liver in most cases (11/12, 92 %; 11/12, 92 %, respectively), whereas MRP3
      focally overexpressed in 75 % (9/12) of cases. CONCLUSION: FNH and FNH-like
      nodules revealed equal or stronger OATP8 expression than background liver. OATP8
      expression showed significant correlation with signal intensity on the HB phase.

PMID- 22618455
TI  - The effect of the postmortem interval on the redistribution of drugs: a
      comparison of mortuary admission and autopsy blood specimens.
AB  - Postmortem redistribution (PMR) is an accepted toxicological phenomenon that may
      affect the interpretation of postmortem blood concentrations. The extent of PMR
      is not well understood for some drugs. This report describes the PMR of selected
      substances resulting from the analysis of 149 cases comparing blood specimens
      taken at admission of the deceased to the mortuary and then at autopsy. Blood was
      collected in preserved tubes containing 1 % sodium fluoride/potassium oxalate.
      All cases were subject to a full autopsy and blood extracts were analyzed using a
      targeted screen by LC-MS/MS. 30 drug or drug metabolites that were detected with
      an incidence of 6 or more were included in this study. The pre-autopsy interval
      ranged from 0.5 to 164 h (6.4 days) with an average of 64 h for the cases
      analyzed. The increase in drug concentration from mortuary admission to autopsy
      ranged from 30 % for drugs such as citalopram, mirtazapine, and sertraline to 300
      % for doxylamine. Only 7 drugs of the 30 studied showed increases of greater than
      20 % when comparing autopsy to mortuary admission blood irrespective of the
      length of the postmortem interval. Drugs including methadone, EDDP, fluoxetine,
      mirtazapine, and sertraline all showed statistically significant increases during
      the pre-autopsy interval (p < 0.05) while 6-acetylmorphine, 9-hydroxy
      risperidone, and caffeine showed significant decreases (p < 0.05) from mortuary
      admission to autopsy. While femoral blood is thought to reduce PMR, this data
      shows that for some drugs significant redistribution can occur even when taking
      peripheral specimens irrespective of the delay in the postmortem interval.

PMID- 22618457
TI  - The effects of solvent on switchable stereoselectivity: copper-catalyzed
      asymmetric conjugate additions using D2-symmetric biphenyl phosphoramidite
      ligands.
AB  - A highly enantioselective copper-catalyzed conjugate addition of diethylzinc to
      acyclic aromatic enones was developed with phosphoramidite ligands bearing a D(2)
      symmetric biphenyl backbone. This type of reaction demonstrated that toluene and
      THF solvents can completely reverse the absolute configuration of the products,
      thus simplifying the process of accessing either enantiomer (S: 92% ee, 94%
      yield; R: 99% ee, 96% yield).

PMID- 22618469
TI  - Individualization of a pharmacokinetic model by fractional and nonlinear fit
      improvement.
AB  - This study presents application of a new linear and nonlinear fractional
      derivative two compartmental model to the evaluation of individual
      pharmacokinetics. In the model, the integer order derivatives are replaced by
      derivatives of real order. A specific nonlinear function is used for the fit
      improvement of a fractional derivative two compartmental model with the mass
      balance conservation. The agreement of the values predicted by the proposed model
      with the values obtained through experiments with bumetanide tablets in human
      volunteers is shown to be good. Thus, pharmacokinetics of bumetanide can be
      described well by a linear or a nonlinear two compartmental model with fractional
      derivatives of the same order proposed here. Parameters in the model are
      determined by the least squares method and the particle swarm optimization
      numerical procedure is used. The results show that the linear fractional order
      two compartmental model for bumetanide is useful improvement of the classical
      (integer order) two compartmental model and that the nonlinear fractional order
      model is useful improvement of the linear model in a great number of volunteers.

PMID- 22618471
TI  - Environmental digest.

PMID- 22618468
TI  - [Postoperative cognitive dysfunction. Possible neuronal mechanisms and practical
      consequences for clinical routine].
AB  - Postoperative cognitive dysfunction (POCD) presents as a long-lasting decline in
      cognitive function after a surgical procedure, predominantly occurring in elderly
      patients. The causes are most likely multifactorial with the exact mechanisms
      still unknown. Hypotheses of the causes of POCD are based on experimental
      evidence that anesthetics can impair mechanisms of learning and memory on a
      neuronal level and might lead to neurodegeneration. Additionally, surgery can
      result in neuroinflammation which could also underlie POCD. The most important
      strategy to avoid POCD is to maintain the patient's physiological homeostasis
      perioperatively. According to the presently available clinical studies
      recommendations in favor or against certain anesthesiological procedures cannot
      be given.

PMID- 22618470
TI  - Hand immobilization affects arm and shoulder postural control.
AB  - It is a common experience, immediately after the removal of a cast or a splint,
      to feel motor awkwardness, which is usually attributed to muscular and joint
      immobilization. However, the same feeling may also be perceived after a brief
      period of immobilization. We provide evidence that this last effect stems from
      changes in the cortical organization of the focal movement as well as in the
      associated anticipatory postural adjustments. Indeed, these two aspects of the
      motor act are strongly correlated, although scaled in different manners. In fact,
      they are both shaped in the primary motor cortex, they both undergo similar
      amplitude and latency modulation and, as we will show, they are both impaired by
      the immobilization of the lone prime mover. Neuromuscular effects of limb
      immobilization are well known; however, most papers focus on changes occurring in
      the pathways projecting to the prime mover, which acts on the immobilized joint.
      Conversely, this study investigates the effect of immobilization on anticipatory
      postural adjustments. Indeed, we show that 12 h of wrist and fingers
      immobilization effectively modify anticipatory postural adjustments of the elbow
      and the shoulder, that is, those joints not immobilized within the fixation
      chain. Accordingly, the motor impairment observed after short-term immobilization
      most likely stems from the unbalance between anticipatory postural adjustments
      and the focal movement.

PMID- 22618472
TI  - [Simple and yet so difficult: common occurrence of fibrous dysplasia and myxomas 
      the Mazabraud syndrome].

PMID- 22618473
TI  - [Application of MR/PET in oncologic imaging].
AB  - The present review aims to depict the possibilities offered by hybrid imaging
      with magnetic resonance positron emission tomography (MR/PET). Recently, new
      whole-body MR/PET scanners were introduced allowing for the combination of both
      modalities outside the brain. This is a challenge for both modalities: For MRI,
      it is essential to provide anatomical images with high resolution. Additionally,
      diffusion-weighted imaging (DWI), proton spectroscopy, but also dynamic contrast
      enhanced imaging plays an important role. With regard to PET, the technical
      challenge mainly consists of obtaining an appropriate MR-based attenuation
      correction for the PET data. Using MR/PET, it is possible to acquire
      morphological and functional data in one examination. In particular, children and
      young adults will benefit from this new hybrid technique, especially in oncologic
      imaging with multiple follow-up examinations. However, it is expected that PET/CT
      will not be replaced completely by MR/PET because PET/CT is less cost-intensive
      and more widely available. Moreover, in lung imaging, MRI limitations still have
      to be accepted. Concerning research, simultaneous MR/PET offers a variety of new
      possibilities, for example cardiac imaging, functional brain studies or the
      evaluation of new tracers in correlation with specific MR techniques.

PMID- 22618474
TI  - [Experiences with ultrasound-guided port implantations via the lateral subclavian
      vein: a retrospective analysis of 1532 patients].
AB  - PURPOSE: Evaluation of the success and complication rates in ultrasound-guided
      central venous port implantations through the lateral subclavian vein. MATERIALS
      AND METHODS: A total of 1537 subcutaneous central venous ports were implanted in
      1532 patients. The catheter remained in place for a mean duration of 202 days
      (overall 309,464 catheter days). A retrospective analysis within the hospital and
      radiological information system (HIS/RIS) was performed to assess technical
      success and complication rates. RESULTS: The implantations of the central venous
      ports were performed by 21 radiologists (19 residents). The technical success
      rate was 99.0 % (1517/1537) and the overall complication rate was 8.5 %
      (130/1537; 0.42 per 1000 catheter days). Procedural and acute complications (< 24
      h) occurred in 22 of 1532 patients (1.4 %). Follow-up revealed 45 port
      explantations ahead of time due to complications in the early (< 30 d) or late (>
      31 d) post-interventional period (2.9 %; 0.15 per 1000 catheter days). Catheter
      associated vein thrombosis was the most common complication (n = 60, 3.9 %, 0.19
      per 1000 catheter days). CONCLUSION: Ultrasound-guided insertion of central
      venous port catheters through the lateral subclavian vein provides safe vascular
      access. Procedural complication rate is low with special regard to post-graduate
      training. The most common reasons for early port explantations were catheter
      associated infections and vessel occlusions.

PMID- 22618475
TI  - [Tracheal metastasis of a cutaneous malignant melanoma].

PMID- 22618476
TI  - Application of classification trees for the qualitative differentiation of focal
      liver lesions suspicious for metastasis in gadolinium-EOB-DTPA-enhanced liver MR
      imaging.
AB  - PURPOSE: To evaluate the diagnostic accuracy of qualitative descriptors alone and
      in combination for the classification of focal liver lesions (FLLs) suspicious
      for metastasis in gadolinium-EOB-DTPA-enhanced liver MR imaging. MATERIALS AND
      METHODS: Consecutive patients with clinically suspected liver metastases were
      eligible for this retrospective investigation. 50 patients met the inclusion
      criteria. All underwent Gd-EOB-DTPA-enhanced liver MRI (T2w, chemical shift T1w,
      dynamic T1w). Primary liver malignancies or treated lesions were excluded. All
      investigations were read by two blinded observers (O1, O2). Both independently
      identified the presence of lesions and evaluated predefined qualitative lesion
      descriptors (signal intensities, enhancement pattern and morphology). A reference
      standard was determined under consideration of all clinical and follow-up
      information. Statistical analysis besides contingency tables (chi square, kappa
      statistics) included descriptor combinations using classification trees (CHAID
      methodology) as well as ROC analysis. RESULTS: In 38 patients, 120 FLLs (52
      benign, 68 malignant) were present. 115 (48 benign, 67 malignant) were identified
      by the observers. The enhancement pattern, relative SI upon T2w and late enhanced
      T1w images contributed significantly to the differentiation of FLLs. The overall
      classification accuracy was 91.3 % (O1) and 88.7 % (O2), kappa = 0.902.
      CONCLUSION: The combination of qualitative lesion descriptors proposed in this
      work revealed high diagnostic accuracy and interobserver agreement in the
      differentiation of focal liver lesions suspicious for metastases using Gd-EOB
      DTPA-enhanced liver MRI.

PMID- 22618477
TI  - A scoring system for the assessment of angiographic findings in non-occlusive
      mesenteric ischemia (NOMI).
AB  - PURPOSE: To establish a standardized scoring system for angiographic findings in
      patients with non-occlusive mesenteric ischemia (NOMI). MATERIALS AND METHODS: In
      36 patients (mean age: 72 years), 53 angiographies of the superior mesenteric
      artery (SMA) were performed for suspected NOMI after cardiac or major aortic
      surgery. All examinations were performed using a standardized DSA technique. Two
      experienced radiologists performed a consensus reading blinded to the clinical
      information, on two occasions with an interval of two weeks. In order to
      investigate the reproducibility of the criteria, the images were assessed once by
      an intensivist and a medical student. Image analysis was performed with respect
      to vessel morphology, reflux of contrast medium into the aorta, small bowel
      parenchymal contrast enhancement and distension and the delay between arterial
      injection and portal vein filling. RESULTS: Almost perfect intra-observer
      correlation was obtained for the assessment of the contrast medium reflux (kappa
      = 0.82) and substantial correlation for the time of portal vein filling (kappa =
      0.66). Moderate correlations were obtained for the vessel morphology (kappa =
      0.51), small bowel enhancement (kappa = 0.63) and distension (kappa = 0.53).
      Contrast medium reflux into the aorta (kappa = 0.77 and 0.63) and the time of
      portal vein filling (kappa = 0.42 and 0.58) resulted in the highest inter
      observer correlations between the radiologists and the intensivist as well as the
      radiologists and the student. CONCLUSION: In patients with suspected NOMI, using
      our scoring system yields high intra- and inter-observer correlations, allowing a
      standardized evaluation of angiographic findings.

PMID- 22618478
TI  - MSCT follow-up in malignant lymphoma: comparison of manual linear measurements
      with semi-automated lymph node analysis for therapy response classification.
AB  - PURPOSE: Assignment of semi-automated lymph node analysis compared to manual
      measurements for therapy response classification of malignant lymphoma in MSCT.
      MATERIALS AND METHODS: MSCT scans of 63 malignant lymphoma patients before and
      after 2 cycles of chemotherapy (307 target lymph nodes) were evaluated. The long
      axis diameter (LAD), short axis diameter (SAD) and bi-dimensional WHO were
      determined manually and semi-automatically. The time for manual and semi
      automatic segmentation was evaluated. The ref. standard response was defined as
      the mean relative change across all manual and semi-automatic measurements (mean
      manual/semi-automatic LAD, SAD, semi-automatic volume). Statistical analysis
      encompassed t-test and McNemar's test for clustered data. RESULTS: Response
      classification per lymph node revealed semi-automated volumetry and bi
      dimensional WHO to be significantly more accurate than manual linear metric
      measurements. Response classification per patient based on RECIST revealed more
      patients to be correctly classified by semi-automatic measurements, e. g. 96.0
      %/92.9 % (WHO bi-dimensional/volume) compared to 85.7/84.1 % for manual LAD and
      SAD, respectively (mean reduction in misclassified patients of 9.95 %).
      Considering the use of correction tools, the time expenditure for lymph node
      segmentation (29.7 +/- 17.4 sec) was the same as with the manual approach (29.1
      +/- 14.5 sec). CONCLUSION: Semi-automatically derived "lymph node volume" and "bi
      dimensional WHO" significantly reduce the number of misclassified patients in the
      CT follow-up of malignant lymphoma by at least 10 %. However, lymph node
      volumetry does not outperform bi-dimensional WHO.

PMID- 22618479
TI  - [Automated detection and volumetric segmentation of the spleen in CT scans].
AB  - PURPOSE: To introduce automated detection and volumetric segmentation of the
      spleen in spiral CT scans with the THESEUS-MEDICO software. The consistency
      between automated volumetry (aV), estimated volume determination (eV) and manual
      volume segmentation (mV) was evaluated. MATERIALS AND METHODS: Retrospective
      evaluation of the CAD system based on methods like "marginal space learning" and
      "boosting algorithms". 3 consecutive spiral CT scans (thoraco-abdominal; portal
      venous contrast agent phase; 1 or 5 mm slice thickness) of 15 consecutive
      lymphoma patients were included. The eV: 30 cm3 + 0.58 (width * length *
      thickness of the spleen) and the mV as the reference standard were determined by
      an experienced radiologist. RESULTS: The aV could be performed in all CT scans
      within 15.2 (+/- 2.4) seconds. The average splenic volume measured by aV was
      268.21 +/- 114.67 cm3 compared to 281.58 +/- 130.21 cm3 in mV and 268.93 +/-
      104.60 cm3 in eV. The correlation coefficient was 0.99 (coefficient of
      determination (R2) = 0.98) for aV and mV, 0.91 (R2 = 0.83) for mV and eV and 0.91
      (R2 = 0.82) for aV and eV. There was an almost perfect correlation of the changes
      in splenic volume measured with the new aV and mV (0.92; R2 = 0.84), mV and eV
      (0.95; R2 = 0.91) and aV and eV (0.83; R2 = 0.69) between two time points.
      CONCLUSION: The automated detection and volumetric segmentation software rapidly
      provides an accurate measurement of the splenic volume in CT scans. Knowledge
      about splenic volume and its change between two examinations provides valuable
      clinical information without effort for the radiologist.

PMID- 22618480
TI  - Optimizing image quality and dose for digital radiography of distal pediatric
      extremities using the contrast-to-noise ratio.
AB  - PURPOSE: To investigate the influence of X-ray tube voltage and filtration on
      image quality in terms of contrast-to-noise ratio (CNR) and dose for digital
      radiography of distal pediatric extremities and to determine conditions that give
      the best balance of CNR and patient dose. MATERIALS AND METHODS: In a phantom
      study simulating the absorption properties of distal extremities, the CNR and the
      related patient dose were determined as a function of tube voltage in the range
      40 - 66 kV, both with and without additional filtration of 0.1 mm Cu/1 mm Al. The
      measured CNR was used as an indicator of image quality, while the mean absorbed
      dose (MAD) - determined by a combination of measurement and simulation - was used
      as an indicator of the patient dose. RESULTS: The most favorable relation of CNR
      and dose was found for the lowest tube voltage investigated (40 kV) without
      additional filtration. Compared to a situation with 50 kV or 60 kV, the mean
      absorbed dose could be lowered by 24 % and 50 %, respectively, while keeping the
      image quality (CNR) at the same level. CONCLUSION: For digital radiography of
      distal pediatric extremities, further CNR and dose optimization appears to be
      possible using lower tube voltages. Further clinical investigation of the
      suggested parameters is necessary.

PMID- 22618481
TI  - Intraoperative specimen radiography in patients with nonpalpable malignant breast
      lesions.
AB  - PURPOSE: Specimen mammography of nonpalpable wire-localized breast lesions is the
      standard in breast-conserving surgery. The aim of this study was to evaluate the
      reliability of intraoperative 2-view specimen mammography in different cancer
      types. MATERIALS AND METHODS: After ethics approval, 3 readers retrospectively
      evaluated margins on 266 2-view specimen radiographs. They determined the closest
      margin and the orientation. The results were correlated with the histopathology
      (intra-class correlation coefficient [ICC] and contingency coefficient [CC]) and
      compared (Wilcoxon test). RESULTS: Invasive ductal carcinoma (IDC) with ductal
      carcinoma in situ (DCIS) was present in 115 (43 %), IDC in 75 (28 %), invasive
      lobular carcinoma (ILC) in 57 (22 %) and rare cancers (CA) in 19 specimens (7 %).
      The sensitivity/specificity and positive/negative predictive value (P/NPV) of
      specimen mammography were 0.50/0.86 and 0.86/0.50 for CA, 0.42/0.68 and 0.48/0.63
      for IDC, 0.36/0.81 and 0.69/0.51 for ILC, and 0.22/0.78 and 0.68/0.32 for
      IDC+DCIS. Readers correctly identified the orientation of the closest margin in
      at least one view in an average of 149 specimens (56 %). CCs were between 0.680
      (IDC) and 0.912 (CA), suggesting a moderate correlation between radiographic and
      histological orientation. The correlations were worse for the radiographic and
      histological distances, with ICC ranging from 0.238 (ILC) to 0.475 (CA). The
      Wilcoxon test revealed overestimation of the radiographic margins compared to the
      histological ones for DCIS. CONCLUSION: Our results suggest that specimen
      radiography has relatively good overall specificity and good PPV, while the
      sensitivity and NPV are low for DCIS. A negative result on specimen radiography
      does not rule out histologically involved margins.

PMID- 22618482
TI  - Typical cardiac MRI findings of a prominent crista terminalis mimicking a right
      atrial mass on echocardiography.

PMID- 22618483
TI  - Incidental findings in paranasal sinuses and mastoid cells: a cross-sectional
      magnetic resonance imaging (MRI) study in a pediatric radiology department.
AB  - PURPOSE: Misdiagnosis of "sinusitis" is still frequent in children, although
      mucosal swelling in the paranasal sinuses of children has been reported as a
      common incidental finding. Recent radiological publications on the problem are
      rare. We prospectively evaluated the mucosal thickening in the paranasal sinuses
      and mastoid cells of children who underwent MRI of the head for reasons other
      than sinusitis or mastoiditis. MATERIALS AND METHODS: 147 patients, 0.2 - 22.7
      years, median 8.9. Axial and sagittal T2 TSE images were evaluated by two
      experienced pediatric radiologists. Categories for the degree of mucosal swelling
      were for the maxillary, frontal and sphenoid sinuses: no swelling, minor: < 5 mm,
      or major: >= 5 mm; for ethmoid cells and mastoid cells: not present, minor: <= 50
      % of cells, or major: > 50 %. RESULTS: 61 % of children had one or more salient
      findings in their paranasal sinuses or mastoid cells. 48 % had mucosal swelling
      in their paranasal cavities, 25 % in their mastoid cells. The prevalence was
      higher among children less than 10 years of age (60 % and 42 %) and among
      children with current upper respiratory tract infection (71 % and 35 %). There
      was no correlation to a history of headache, snoring, asthma and allergies, or to
      gender or place of residence. CONCLUSION: Mucosal swelling in paranasal sinuses
      and in mastoid cells is a frequent incidental finding in children. Even major
      mucosal swelling in a paranasal sinus is not necessarily a sign of infection. In
      radiological reports the terms "sinusitis" and "mastoiditis" should therefore be
      used with great caution. The initiation of treatment should be based on clinical
      symptoms and not on radiological abnormalities alone.

PMID- 22618484
TI  - Glioblastomas vs. lymphomas: more diagnostic certainty by using susceptibility
      weighted imaging (SWI).
AB  - PURPOSE: It can be difficult to differentiate glioblastomas from lymphomas using
      only standard MR images. There are references suggesting that it might be
      possible to differentiate these tumors using susceptibility-weighted imaging
      (SWI). The purpose of this study is to prove the diagnostic benefit using
      susceptibility-weighted images. MATERIAL AND METHODS: Three neuroradiologists
      tried to differentiate 4 histologically verified lymphomas from 11 glioblastomas
      in retrospect. They first viewed the conventional MR images and declared a
      diagnosis with a grade of certainty. Afterwards they additionally reviewed the
      susceptibility-weighted images. RESULTS: Glioblastomas have a clearly higher
      grade of susceptibility signals than lymphomas. By additionally using
      susceptibility-weighted images, the radiologists determined the correct diagnosis
      in 82.2 % of the cases. Without susceptibility-weighted images, the diagnosis was
      correct in 75.5 % of the cases. The subjective gain of certainty was 16.5 %. If
      there were no intratumoral susceptibility signals (ITSS) (grade 1), the
      sensitivity for diagnosing a lymphoma was 70 % and the specificity was 100 %. The
      sensitivity for diagnosing a glioblastoma was 90.5 % and the specificity was 100
      % if there was a high rate of intratumoral susceptibility signals (grade 3).
      CONCLUSION: Susceptibility-weighted images are an additional tool in clinical
      practice for determining the correct diagnosis. The differentiation between
      glioblastomas and lymphomas and the certainty of the determined diagnosis are
      better. Therefore, we recommend adding susceptibility-weighted imaging to the
      clinical MR tumor protocol.

PMID- 22618485
TI  - [Successful prophylactic embolization of an intrahepatic pseudoaneurysm after
      split liver transplantation].

PMID- 22618486
TI  - Potassium-doped graphene enhanced electrochemiluminescence of SiO(2)@CdS
      nanocomposites for sensitive detection of TATA-binding protein.
AB  - Based on the amplified signal from SiO(2)@CdS nanocomposites integrated with K
      doped graphene, a new electrochemiluminescence biosensor was developed for the
      successful detection of transcription factor TATA-binding protein (TBP).

PMID- 22618487
TI  - In vitro susceptibility of high virulence microorganisms isolated in heart valve
      banking.
AB  - Storage preparation of human heart valves for implants generally includes
      incubation in an antimicrobial disinfection solution and cryopreservation.
      Changes in patterns of microorganisms susceptibility to antibiotics is a variable
      process of that promote its inefficiency. The aim of this study has been an
      evaluation of in vitro susceptibility of high virulence microorganisms isolated
      in our tissue bank for 14 years in order to evaluate the efficiency, and to
      promote changes for further antibiotics mixtures as well. Data presented in this
      study show that microorganisms isolates in valve banking display susceptibility
      patterns similar to those shown in other clinical circumstances, and the most
      commonly used antibiotics regimes are useful to date. An antibiotic cocktail
      containing aminoglicoside in addition to ciprofloxacin and vancomycin is an
      efficient mixture to be used in valve banking. Further studies will be necessary
      for monitoring patterns changes of in vitro susceptibility of microbiological
      isolates in tissue banking.

PMID- 22618488
TI  - Isolated lithium sites supported on mesoporous silica: a novel solid strong base
      with high catalytic activity.
AB  - Isolated lithium sites were anchored on mesoporous silica by a molecular
      precursor approach at room temperature. The resultant materials exhibit ordered
      mesostructure, high base strength, and more importantly, a molecular-level
      dispersion of active sites, which are extremely desirable for catalysis and
      impossible to be realized by conventional methods.

PMID- 22618489
TI  - Behavioral economics: the key to closing the gap on maternal, newborn and child
      survival for Millennium Development Goals 4 and 5?
AB  - Millennium Development Goals (MDGs) 4 and 5 set ambitious targets to reduce
      maternal, newborn and child mortality by 2015. With 2015 fast approaching, there
      has been a concerted effort in the global health community to "close the gap" on
      the MDG targets. Recent consensus initiatives and frameworks have refocused
      attention on evidence-based, low-cost interventions that can reduce mortality and
      morbidity, and have argued for additional funding to increase access to and
      coverage of these life-saving interventions. However, funding alone will not
      close the gap on MDGs 4 and 5. Even when high-quality, affordable products and
      services are readily available, uptake is often low. Progress will therefore
      require not just money, but also advances in health-related behavior change and
      decision-making. Behavioral economics offers one way to achieve real progress by
      improving our understanding of how individuals make choices under information and
      time constraints, and by offering new approaches to make it easier for
      individuals to do what is in their best interest and harder to do what is not. We
      introduce five behavioral economic principles and demonstrate how they could
      boost efforts to improve maternal, newborn, and child health in pursuit of MDGs 4
      and 5.

PMID- 22618490
TI  - Maternal mortality in the Islamic Republic of Iran: on track and in transition.
AB  - The Maternal Mortality Ratio is an important public health indicator that
      reflects both the quality of a health care system and the role of women within
      that society. In September 2000 the United Nations Millennium Declaration
      outlined the eight Millennium Development Goals (MDGs) that set targets to be
      achieved by 2015. MDG 5 focused on improving maternal health. It had two clear
      subgoals: to reduce maternal mortality globally by three quarters between 1990
      and 2015 and to obtain universal access to reproductive health for women. Despite
      a global trend of declining maternal mortality only a handful of nations are
      currently 'on track' to achieve their MDG targets by 2015. The Islamic Republic
      of Iran is one of these nations. In just over three decades, Iran has undergone
      demographic transition with significant reductions in total fertility and
      population growth rates. In concert with this transition, Iran has achieved a
      dramatic decline in the maternal mortality ratio that has fallen to a rate
      comparable with developed nations. Significantly Iran has also experienced a
      paradigm shift in its major causes of maternal mortality from those
      characteristic of developing nations (postpartum haemorrhage, infection) to
      causes more commonly seen in developed nations (pulmonary embolus, stroke). There
      is no single explanation that may account for this transition, rather it is the
      product of a number of different initiatives that have incorporated family
      planning, grass roots focus and wider improvements within the health care system
      of Iran over the past three decades. However the experience of this nation may
      provide a useful example to other developing countries looking to reduce maternal
      mortality.

PMID- 22618491
TI  - Is there a difference in systemic lupus erythematosus with and without Raynaud's
      phenomenon?
AB  - The aim of this study was to assess the association between Raynaud's phenomenon
      (RP) and specific capillaroscopic findings in patients with SLE and particular
      clinical manifestations of the disease. A total of 79 patients with SLE were
      included in the study: 44 of them (43 women) with RP and 35 (32 women) age-, sex
      , and disease-duration-matched patients with SLE without RP. Demographic
      variables, clinical manifestations, laboratory and nailfold capillaroscopy
      findings were compared between the two groups. Central nervous systemic
      involvements (P = 0.0038) and peripheral neuropathy (P = 0.0336) were
      significantly more common in SLE patients with RP, while secondary Sjogren's
      syndrome (P = 0.0363) was more common in SLE patients without RP. RP occurred in
      52 % of patients before SLE onset while 48 % of patients developed RP after they
      had been diagnosed with SLE. Arthritis/arthralgia (P = 0.0073) was significantly
      more common in patients who had been diagnosed with RP before the onset of SLE,
      while mucosal ulcers were more common in patients who contracted RP after the
      onset of SLE (P = 0.0258). Enlarged capillaries (P = 0.0482), presence of
      avascular areas (P = 0.0476), capillary hemorrhages (P = 0.0482), and granular
      blood flow (P = 0.0482) were more common in patients with SLE who also suffered
      from RP, than in patients with SLE without RP. The frequency of normal (63.6 vs.
      82.9 %, P = 0.100) and nonspecific (25 vs. 17.1 %, P = 0.5696) capillaroscopy
      findings were similar in either groups. Scleroderma-like pattern of
      capillaroscopy finding was only found in patients with RP [(11.4 %), P = 0.0482].
      RP in our patients with SLE was associated with specific clinical manifestations,
      indicating that prognostic relevance of RP in SLE should be evaluated.

PMID- 22618492
TI  - Study of N1-alkylation of indoles from the reaction of 2(or 3)-aminoindole-3-(or
      2)carbonitriles with DMF-dialkylacetals.
AB  - The condensation of 2-aminoindole-3-carbonitriles and their 3-aminoindole-2
      carbonitrile isomers with various DMF-dialkoxyacetals was investigated under
      microwaves. The appearance of reactive and versatile alkoxyiminium species
      allowed convenient access to indole precursors of building blocks with potential
      biological activity. The experimental results have been rationalised using DFT
      calculations of theoretical descriptors based on the electrostatic potential.

PMID- 22618509
TI  - miRNAs expression profiling to distinguish lung squamous-cell carcinoma from
      adenocarcinoma subtypes.
AB  - PURPOSE: We investigated whether miRNA expression profiles can distinguish and
      predict outcome of non-small-cell lung carcinoma (NSCLC) patients with different
      histological subtypes. METHODS: High-throughput microarray was used to measure
      miRNA expression levels in six NSCLC samples. Subsequently, quantitative reverse
      transcription polymerase chain reaction (qRT-PCR) was used to verify findings in
      an independent set of 54 squamous-cell lung carcinomas (SCC), 51 lung
      adenocarcinomas (AD), and paired adjacent non-neoplastic lung tissue. RESULTS: We
      showed that, compared to adjacent non-neoplastic lung tissues, the expressions of
      miR-125a-5p and let-7e were decreased in AD and SCC samples, while increased
      expressions of miR-93, miR-205, and miR-221 were observed in SCC samples. In
      addition, miR-205 expression was significantly higher in SCC patients with lymph
      node metastasis. Lower let-7e expression was associated with lymph node
      metastasis, >3 cm tumor size, and differentiation of the NSCLC AD subtype. High
      levels of miR-100 expression also correlated with the AD subtype in current
      smokers. Moreover, induction of miR-93 and miR-205 expressions and reduction of
      let-7e were strongly associated with shorter overall survival in SCC patients,
      whereas AD patient survival was only associated with reduced let-7e. CONCLUSIONS:
      We identified differential expression profiles of miRNAs in AD and SCC. More
      importantly, in addition to morphology and immunocytochemistry approaches, we
      report that miR-93, miR-205, miR-221, and let-7e may represent novel biomarkers
      for differential diagnosis and prognosis of certain NSCLC subtypes or be new
      targets of histology-specific treatments. Furthermore, our results suggest a
      strong correlation between high expression of miR-100 and AD patients with
      history of heavy smoking.

PMID- 22618510
TI  - Enhanced photocatalytic activity of nc-TiO2 by promoting photogenerated electrons
      captured by the adsorbed oxygen.
AB  - Nanocrystalline TiO2 (nc-TiO2) was modified by a simple post treatment with
      monometallic sodium orthophosphate solution. It is shown that the surface
      modification with an appropriate amount of phosphate obviously enhances the
      surface photovoltage responses of nc-TiO2 in the presence of O2, clearly
      indicating that the separation of photogenerated charges is greatly improved by
      promoting the photoelectrons captured by the adsorbed O2. This is well
      responsible for its much high photocatalytic activity for degrading
      representative gas-phase acetaldehyde, liquid-phase phenol and rhodamine B of
      phosphate-modified nc-TiO2, compared with the unmodified nc-TiO2. Moreover, it is
      demonstrated that the amount of O2 adsorbed on the surfaces of nc-TiO2 is greatly
      increased after phosphate modification based on the O2 temperature programmed
      desorption curves, which is attributed to the substitution of -Ti-OH with -Ti-O-P
      OH. It is suggested for the first time that the phosphate modification favors the
      O2 adsorbed on TiO2 so as to further promote the photogenerated electrons
      captured. This work would provide feasible routes to further improve the
      photocatalytic performance for degrading pollutants of oxide-based
      semiconductors. 

PMID- 22618512
TI  - Natural molecular fragments, functional groups, and holographic constraints on
      electron densities.
AB  - One of the tools of the shape analysis of molecular electron densities, the
      Density Threshold Progression Approach used in Shape Group studies can also serve
      as a criterion for the selection of "natural" molecular fragments, relevant to
      functional group comparisons, reactivity studies, as well as to the study of
      levels of relative "autonomy" of various molecular regions. The relevance of
      these approaches to the fragment-based studies of large molecules, such as
      biopolymers and nanostructures is emphasized, and the constraints represented by
      the holographic electron density theorem to this and alternative recent fragment
      approaches are discussed. The analogies with potential energy hypersurface
      analysis using the Energy Threshold Progression Approach and connections to level
      set methods are discussed, and the common features of these seemingly distant
      problems are described. 

PMID- 22618511
TI  - Computational design of improved two-photon active caging compounds based on
      nitrodibenzofuran.
AB  - Nitrodibenzofuran (NDBF) has recently been established as photolabile protecting
      group and efficiently used as two-photon active cage. In this work, a
      computational approach is exploited to rationally design improved two-photon
      active caging groups based on this NDBF chromophore. For this objective, first
      the two-photon absorption (TPA) properties of NDBF are investigated in detail and
      a suitable theoretical approach for the reliable simulation of TPA spectra of
      this class of compounds is identified. Then, virtual chemical modifications are
      performed by introduction of substituents at the chromophore and replacement of
      the central furan ring by pyrolle, thiophene, and borrole heterocycles.
      Subsequently, the TPA properties of the resulting compounds are computed, and the
      influences of the chemical modifications on TPA properties investigated in
      detail. The most promising candidates with largely increased two-photon uncaging
      efficiencies are dimethylamino-substituted derivatives of NDBF,
      nitrodibenzopyrrol, and nitrodibenzothiophene.

PMID- 22618513
TI  - Desymmetrization of cyclohexadienones viad-camphor-derived triazolium salt
      catalyzed intramolecular Stetter reaction.
AB  - Enantioselective desymmetrization of cyclohexadienones via a d-camphor-derived
      triazolium salt catalyzed intramolecular Stetter reaction was realized. With 10
      mol% of camphor-derived triazolium salt E and 10 mol% of DIEA, various
      substituted cyclohexadienones proceeded through an intramolecular Stetter
      reaction, affording tricyclic products in moderate to good yields and excellent
      ee.

PMID- 22618514
TI  - Methamphetamine activates nuclear factor kappa-light-chain-enhancer of activated
      B cells (NF-kappaB) and induces human immunodeficiency virus (HIV) transcription
      in human microglial cells.
AB  - Human immunodeficiency virus (HIV) primarily infects glial cells in the central
      nervous system (CNS). Recent evidence suggests that HIV-infected individuals who
      abuse drugs such as methamphetamine (METH) have higher viral loads and experience
      more severe neurological complications than HIV-infected individuals who do not
      abuse drugs. The aim of this study was to determine the effect of METH on HIV
      expression from the HIV long terminal repeat (LTR) promoter and on an HIV
      integrated provirus in microglial cells, the primary host cells for HIV in the
      CNS. Primary human microglial cells immortalized with SV40 T antigen (CHME-5
      cells) were cotransfected with an HIV LTR reporter and the HIV Tat gene, a key
      regulator of viral replication and gene expression, and exposed to METH. Our
      results demonstrate that METH treatment induced LTR activation, an effect
      potentiated in the presence of Tat. We also found that METH increased the nuclear
      translocation of the nuclear factor kappa B (NF-kappaB), a key cellular
      transcriptional regulator of the LTR promoter, and the activity of an NF-kappaB
      specific reporter plasmid in CHME-5 cells. The presence of a dominant-negative
      regulator of NF-kappaB blocked METH-related activation of the HIV LTR.
      Furthermore, treatment of HIV-latently infected CHME-5 (CHME-5/HIV) cells with
      METH induced HIV expression and nuclear translocation of the p65 subunit of NF
      kappaB. These results suggest that METH can stimulate HIV gene expression in
      microglia cells through activation of the NF-kappaB signaling pathway. This
      mechanism may outline the initial biochemical events leading to the observed
      increased neurodegeneration in HIV-positive individuals who use METH.

PMID- 22618517
TI  - Dimethylamino parthenolide enhances the inhibitory effects of gemcitabine in
      human pancreatic cancer cells.
AB  - INTRODUCTION: Gemcitabine is standard treatment for pancreatic cancer but has
      limited clinical benefit due to chemoresistance. Nuclear factor-kappaB (NF
      kappaB) can promote chemoresistance and is therefore an attractive therapeutic
      target. We hypothesize that NF-kappaB suppression with the novel, orally
      bioavailable inhibitor dimethylamino parthenolide (DMAPT) will sensitize
      pancreatic cancer cells to gemcitabine. METHODS: BxPC-3, PANC-1, and MIA PaCa-2
      human pancreatic cancer cell lines were treated with gemcitabine and/or DMAPT.
      Effects on the NF-kappaB pathway were determined by electrophoretic mobility
      shift assay, ELISA, or Western blot. Proliferation and apoptosis were measured by
      cell counts and ELISA, respectively. The effect of gemcitabine in vivo was
      determined using a MIA PaCa-2 heterotopic xenograft model. RESULTS: Gemcitabine
      induced NF-kappaB activity in BxPC-3, PANC-1, and MIA PaCa-2 cells and decreased
      the level of the NF-kappaB inhibitor IkappaBalpha in BxPC-3 and PANC-1 cells.
      DMAPT prevented the gemcitabine-induced activation of NF-kappaB. The combination
      of DMAPT/gemcitabine inhibited pancreatic cancer cell growth more than either
      agent alone. Gemcitabine also induced intratumoral NF-kappaB activity in vivo.
      CONCLUSIONS: DMAPT enhanced the anti-proliferative effects of gemcitabine in
      association with NF-kappaB suppression in pancreatic cancer cells in vitro.
      Furthermore, gemcitabine induced NF-kappaB activity in vivo, thus supporting the
      evaluation of NF-kappaB-targeted agents to complement gemcitabine-based
      therapies.

PMID- 22618518
TI  - Lymph node retrieval after preoperative chemoradiotherapy for rectal cancer.
AB  - BACKGROUND: Current guidelines recommend the assessment of at least 12 lymph
      nodes for rectal cancer staging. Preoperative chemoradiotherapy may affect lymph
      node yield in this malignancy. This study investigated the impact of neoadjuvant
      chemoradiotherapy on the number of lymph nodes retrieved from rectal cancer
      patients. METHODS: An analysis of 162 rectal cancer patients who underwent
      curative surgery between 2005 and 2010. Seventy-one patients with stage II or III
      tumors received preoperative chemoradiotherapy. Using multivariate analysis, we
      assessed the correlation between clinicopathologic variables and number of
      retrieved lymph nodes. We also evaluated the association between survival and
      number of lymph nodes obtained. RESULTS: On multivariate analysis, preoperative
      chemoradiotherapy was the only variable to independently affect the number of
      lymph nodes obtained. The mean number of lymph nodes was 14.2 in patients treated
      with preoperative chemoradiotherapy and 19.4 in those not treated (P < 0.001). In
      the chemoradiotherapy group, 29.6 % of patients had fewer than 12 lymph nodes
      obtained compared with 9.9 % in the primary surgery group (P = 0.003). After
      chemoradiation, the number of retrieved lymph nodes was inversely correlated with
      tumor regression grade. Results showed that 5-year overall and disease-free
      survival were similar whether the patient had 12 or more nodes retrieved or not.
      CONCLUSIONS: Preoperative chemoradiotherapy reduces the lymph node yield in
      rectal cancer. The number of retrieved lymph nodes is affected by degree of
      histopathologic response of the tumor to chemoradiation. Thus, number of lymph
      nodes should not be used as a surrogate for oncologic adequacy of resection after
      neoadjuvant chemoradiotherapy for rectal cancer.

PMID- 22618519
TI  - Magnified endoscopy combined with narrow band imaging of minimal superficial
      esophageal neoplasia-indicators to differentiate intraepithelial neoplasias.
AB  - PURPOSE: Clinical application of narrow band imaging facilitates diagnosis of
      esophageal neoplasia. However, no previous investigation has been conducted on
      magnifying endoscopy combined with narrow band imaging in detection of minimal
      superficial esophageal neoplasia, which is defined as neoplasia <10 mm in
      diameter. The aim of this retrospective study was to evaluate the usefulness of
      this combined technique in the differential diagnosis of minimal superficial
      esophageal neoplasia. METHODS: Between January 2005 and November 2011, 53 minimal
      superficial esophageal neoplasias in 40 patients were diagnosed by screening
      upper gastrointestinal endoscopy with narrow band imaging at our hospital. We
      investigated findings including brownish dots, brownish epithelium, and
      demarcation line of minimal superficial esophageal neoplasia diagnosed
      histopathologically as low-grade intraepithelial neoplasia, high-grade
      intraepithelial neoplasia, and squamous cell carcinoma. RESULTS: Significantly
      more brownish dots (P < 0.05) and brownish epithelium (P < 0.005) were observed
      in intraepithelial papillary capillary loops in high-grade neoplasia compared
      with low-grade neoplasia. When minimal superficial esophageal neoplasia was
      diagnosed as high-grade intraepithelial neoplasia or squamous cell carcinoma,
      sensitivity, specificity, positive predictive value, and negative predictive
      value were 88.9, 42.9, 44.4, and 88.2%, respectively, for brownish dots; 94.4,
      51.4, 50.0, and 94.7%, respectively, for brownish epithelium; and 66.7, 62.9,
      48.0, and 78.6%, respectively, for demarcation line. CONCLUSIONS: The combined
      technique was useful in the differential diagnosis of minimal superficial
      esophageal neoplasia.

PMID- 22618520
TI  - Nitroglycerine use in transcatheter arterial (chemo)embolization in patients with
      hepatocellular carcinoma and dual-energy CT assessment of Lipiodol retention.
AB  - OBJECTIVES: To investigate whether the addition of nitroglycerine to
      transcatheter arterial (chemo)embolization (TAE/TACE) can increase the delivery
      and effectiveness of TAE/TACE in patients with hepatocellular carcinoma (HCC) by
      dual-energy CT. METHODS: HCC patients (BCLC stage A or B) were randomized to (n =
      51) or not to (n = 50) receive nitroglycerine and an emulsion of Lipiodol with or
      without doxorubicin, followed by embolization with Gelfoam pledgets. Dual-energy
      CT was performed pre- and 1 to 3 months post-embolization to assess changes in
      tumour diameter and Lipiodol levels in tumours. RESULTS: Median tumour diameter
      decreased from baseline in both groups with and without nitroglycerine (7.11 %
      vs. 12.5 %, respectively), and was statistically significant in the group
      receiving nitroglycerine (P = 0.023). There was no difference between the two
      groups in disease response (P = 0.237). The concentration and percentage of
      Lipiodol retained in tumours were significantly greater in patients treated with
      nitroglycerine compared to those without (median concentration 15.05 mg/mL vs.
      4.40 mg/mL, respectively, P < 0.001; median percentage 82.01 % vs. 36.75 %,
      respectively, P < 0.001). CONCLUSIONS: Nitroglycerine increased delivery of the
      Lipiodol emulsion via TAE/TACE to HCC tumours with significant tumour reduction.
      Dual-energy CT can accurately quantify the amount of Lipiodol deposited in
      tumours. KEY POINTS: * Nitroglycerine improves delivery of tumour-targeted
      therapy via enhanced permeability and retention. * In hepatocellular carcinoma,
      nitroglycerine added to TAE/TACE showed greater tumour reduction. * Dual-energy
      CT can reliably quantify the amount of Lipiodol in TAE/TACE.

PMID- 22618521
TI  - Spectral CT in patients with small HCC: investigation of image quality and
      diagnostic accuracy.
AB  - OBJECTIVE: To assess image quality and diagnostic accuracy of monochromatic
      imaging from spectral CT in patients with small HCC (<=3 cm). METHODS: Twenty
      seven patients with 31 HCC underwent spectral CT to generate conventional 140-kVp
      polychromatic images (group A) and monochromatic images with energy levels from
      40 to 140 keV (group B) during the late arterial phase (LAP) and the portal
      venous phase (PVP). Two-sample t tests compared the tumour-to-liver contrast-to
      noise ratio (CNR) and mean image noise. Lesion detection for LAP, reader
      confidence and readers' subjective evaluations of image quality were recorded.
      RESULTS: Highest CNRs in group B were distributed at 40, 50 and 70 keV. Higher
      CNR values and lesion conspicuity scores (LCS) were obtained in group B than in
      group A (CNR 3.36 +/- 2.07 vs. 1.47 +/- 0.89 in LAP; 2.29 +/- 2.26 vs. 1.58 +/-
      1.75 in PVP; LCS 2.82, 2.84, 2.63 and 2.53 at 40-70 keV, respectively, vs. 1.95)
      (P < 0.001). Lowest image noise for group B was at 70 keV, resulting in higher
      image quality than that in group A (4.70 vs. 4.07; P < 0.001). CONCLUSION:
      Monochromatic energy levels of 40-70 keV can increase detectability in small HCC
      and this increase might not result in image quality degradation. KEY POINTS : *
      Spectral computed tomography may help the detection of small hepatocellular
      carcinoma. * Monochromatic energy levels of 40-70 keV increase the sensitivity
      for detection. * Prospective study showed that monochromatic imaging provides
      greater diagnostic confidence. * Monochromatic energy level of 70 keV improves
      the overall image quality.

PMID- 22618522
TI  - The effect of iterative reconstruction on computed tomography assessment of
      emphysema, air trapping and airway dimensions.
AB  - OBJECTIVES: To determine the influence of iterative reconstruction (IR) on
      quantitative computed tomography (CT) measurements of emphysema, air trapping,
      and airway wall and lumen dimensions, compared to filtered back-projection (FBP).
      METHODS: Inspiratory and expiratory chest CTs of 75 patients (37 male, 38 female;
      mean age 64.0 +/- 5.7 years) were reconstructed using FBP and IR. CT emphysema,
      CT air trapping and airway dimensions of a segmental bronchus were quantified
      using several commonly used quantification methods. The two algorithms were
      compared using the concordance correlation coefficient (p (c)) and Wilcoxon
      signed rank test. RESULTS: Only the E/I-ratio(MLD) as a measure of CT air
      trapping and airway dimensions showed no significant differences between the
      algorithms, whereas all CT emphysema and the other CT air trapping measures were
      significantly different at IR when compared to FBP (P < 0.001). CONCLUSION: The
      evaluated IR algorithm significantly influences quantitative CT measures in the
      assessment of emphysema and air trapping. However, the E/I-ratio(MLD) as a
      measure of CT air trapping, as well as the airway measurements, is unaffected by
      this reconstruction method. Quantitative CT of the lungs should be performed with
      careful attention to the CT protocol, especially when iterative reconstruction is
      introduced. KEY POINTS : * New techniques in CT allow numerous quantitative
      measurements of lung function. * Iterative reconstruction influences quantitative
      CT measurements of emphysema and air trapping. * Expiratory-to-inspiratory ratio
      of mean lung density and airway measurements are unaffected by iterative
      reconstruction. * Quantitative lung-CT should be performed with careful attention
      to the CT protocol.

PMID- 22618523
TI  - Brain imaging findings in symptomatic patients after allogeneic haematopoietic
      stem cell transplantation: correlation with clinical outcome.
AB  - OBJECTIVE: To investigate the risk factors for, and the incidence of, structural
      abnormalities on brain imaging in allogeneic haematopoietic stem cell transplant
      (HSCT) patients, and correlate these findings with survival. METHODS: We
      retrospectively reviewed all brain computed tomography (CT) and/or magnetic
      resonance imaging (MRI) studies obtained during the first post-HSCT year from
      2004 thru 2007 in allogeneic HSCT recipients. RESULTS: A total of 128 patients
      had brain imaging in the first post-HSCT year. Forty one of these 128 patients
      (32 %) had structural abnormalities on brain imaging: cerebrovascular
      complications (n = 10), central nervous system (CNS) infection (n = 9), subdural
      fluid collection (n = 6), CNS recurrence of haematological malignancy (n = 11),
      and drug toxicity abnormalities (n = 5). The only significant risk factor for
      structural imaging abnormality was younger patient age (P = 0.01). MRI was
      significantly more likely than CT to provide specific imaging diagnosis of
      cerebral lesions (P = 0.001). HSCT patients with cerebrovascular complications
      have poor survival (P < 0.05). However, overall survival was not significantly
      worse for the 41 patients with the structural imaging abnormalities as compared
      to the 87 patients who had brain imaging but no structural abnormalities.
      CONCLUSIONS: There was no survival difference in patients whose brain imaging was
      normal or abnormal. However, there was poor outcome in patients with
      cerebrovascular complications after HSCT. KEY POINTS : * Brain imaging frequently
      demonstrates neurological complications following haematopoietic stem cell
      transplantation. * Younger HSCT patients are more likely to exhibit abnormal
      brain imaging findings. * HSCT recipients with cerebrovascular complications have
      the worst survival. * However brain imaging results are weak indicators of
      overall survival after HSCT.

PMID- 22618524
TI  - The impact of radiological equipment on patient radiation exposure during
      endovascular aortic aneurysm repair.
AB  - OBJECTIVES: To compare the patient radiation dose during endovascular aortic
      aneurysm repair (EVAR) using different types of radiological systems: a mobile
      fluoroscopic C-arm, mobile angiographic and fixed angiographic equipment.
      METHODS: Dose-area products (DAP) were obtained from a retrospective study of 147
      consecutive patients, subjected to 153 EVAR procedures during a 3.5-year period.
      On the basis of these data, entrance surface dose (ESD) and effective dose (ED)
      were calculated. EVARs were performed using a fluoroscopic C-arm, mobile or fixed
      angiographic equipment in 79, 26 and 48 procedures, respectively. RESULTS:
      Fluoroscopy times were essentially equivalent for all the systems, ranging from
      15 to 19 min. The clinical outcomes were not significantly different among the
      systems. Statistically significant differences among radiological equipment
      grouping were found for DAP (mobile C-arm: 32 +/- 20 Gy cm(2); mobile
      angiography: 362 +/- 164 Gy cm(2); fixed angiography: 464 +/- 274 Gy cm(2); P <
      10(-6)), for ESD (mobile C-arm: 0.18 +/- 0.11 Gy; mobile angiography: 2.0 +/- 0.8
      Gy; fixed angiography: 2.5 +/- 1.5 Gy; P < 10(-6)) and ED (mobile C-arm: 6.2 +/-
      4.5 mSv; mobile angiography: 64 +/- 26 mSv; fixed angiography: 129 +/- 76 mSv; P
      < 10(-6)). CONCLUSIONS: Radiation dose in EVAR is substantially less with a
      modern portable C-arm than with a fixed or mobile dedicated angiographic system.
      KEY POINTS : * Fluoroscopy during endovascular aortic aneurysm repair can impart
      a substantial radiation dose. * Radiation doses during EVAR are higher when using
      mobile/fixed angiographic systems. * Mobile C-arm fluoroscopy imparts a lower
      dose with an equivalent clinical outcome. * Procedures need to be dose-optimised
      when using mobile/fixed angiographic systems.

PMID- 22618527
TI  - The antiphospholipid syndrome: diagnosis, pathogenesis, laboratory testing, and
      management.

PMID- 22618525
TI  - Ouabain-stimulated trafficking regulation of the Na/K-ATPase and NHE3 in renal
      proximal tubule cells.
AB  - We have demonstrated that ouabain regulates protein trafficking of the Na/K
      ATPase alpha1 subunit and NHE3 (Na/H exchanger, isoform 3) via ouabain-activated
      Na/K-ATPase signaling in porcine LLC-PK1 cells. To investigate whether this
      mechanism is species-specific, ouabain-induced regulation of the alpha1 subunit
      and NHE3 as well as transcellular (22)Na(+) transport were compared in three
      renal proximal tubular cell lines (human HK-2, porcine LLC-PK1, and AAC-19
      originated from LLC-PK1 in which the pig alpha1 was replaced by ouabain-resistant
      rat alpha1). Ouabain-induced inhibition of transcellular (22)Na(+) transport is
      due to an ouabain-induced redistribution of the alpha1 subunit and NHE3. In LLC
      PK1 cells, ouabain also inhibited the endocytic recycling of internalized NHE3,
      but has no significant effect on recycling of endocytosed alpha1 subunit. These
      data indicated that the ouabain-induced redistribution of the alpha1 subunit and
      NHE3 is not a species-specific phenomenon, and ouabain-activated Na/K-ATPase
      signaling influences NHE3 regulation.

PMID- 22618526
TI  - Possible involvement of Cyclic-GMP-dependent protein kinase on matrix
      metalloproteinase-2 expression in rat aortic smooth muscle cells.
AB  - Degradation and resynthesis of the extracellular matrix (ECM) are essential
      during tissue remodeling. Expansion of the vascular intima in atherosclerosis and
      restenosis following injury is dependent upon smooth muscle cell (SMC)
      proliferation and migration. The migration of SMC from media to intima critically
      depends on degradation of ECM protein by matrix metalloproteinases (MMPs). MMP
      inhibitors and eNOS gene transfer have been shown to inhibit SMC migration in
      vitro and neointima formation in vivo. Nitric oxide (NO) and cyclic-GMP have been
      implicated in the inhibition of VSMC migration. But, there are few studies
      addressing the role of NO signaling pathways on the expression of MMPs. Here we
      reported the involvement of cyclic-GMP-dependent protein kinase (PKG) (an
      important mediator of NO and cGMP signaling pathway in VSMC) on MMP-2 expression
      in rat aortic SMC. The goal of the present study was to gain insight into the
      possible involvement of PKG on MMP-2 in rat aortic SMC. MMP-2 protein and mRNA
      level and activity were downregulated in PKG-expressing cells as compared to PKG
      deficient cells. In addition, the secretion of tissue inhibitor of
      metalloproteinase-2 (TIMP-2) was increased in PKG-expressing cells as compared to
      PKG-deficient cells. PKG-specific membrane permeable peptide inhibitor (DT-2)
      reverses the process. Interestingly, little or no changes of MMP-9 were observed
      throughout the study. Taken together our data suggest the possible role of PKG in
      the suppression of MMP-2.

PMID- 22618528
TI  - Update on the catastrophic antiphospholipid syndrome and the "CAPS Registry".
AB  - Although less than 1% of patients with the antiphospholipid syndrome (APS)
      develop the catastrophic variant known as catastrophic antiphospholipid syndrome
      (CAPS), its potentially lethal outcome emphasizes its importance in clinical
      medicine today. However, the rarity of this variant makes it extraordinarily
      difficult to study in any systematic way. To collate all the published case
      reports as well as the newly diagnosed cases from all over the world, an
      international registry of patients with CAPS ("CAPS Registry") was created in
      2000 by the European Forum on Antiphospholipid Antibodies
      (www.med.ub.es/MIMMUN/FORUM/CAPS.HTM). Currently, this database documents the
      entire clinical, laboratory, and therapeutic data of more than 350 fully
      registered patients.

PMID- 22618529
TI  - Interference in antiphospholipid antibody assays.
AB  - Antiphospholipid antibodies (aPL) are detected with two types of laboratory
      tests: first, antigen-specific immunoassays for the determination of antibodies
      against cardiolipin, beta2-glycoprotein I and other phospholipids, and
      phospholipid-protein complexes; second, functional (coagulation) assays for the
      detection of lupus anticoagulants. Both aPL immunoassays and coagulation assays
      are prone to interferences, and clinicians need to be aware of the limitations of
      these assays. Interference is a clinically significant bias in the measured
      analyte concentration due to the effect of another component or property of the
      sample. Besides immune-mediated interferences (such as heterophile or human anti
      animal antibodies, rheumatoid factor, high immunoglobulin levels, or factor
      inhibitors), aPL assays are uniquely affected by anticoagulants and the presence
      of residual platelets in test plasma. Interferences are usually analyte- and
      assay-specific and may go unrecognized in routine laboratory practice. Despite
      advances in our knowledge on the mechanisms of interferences in aPL assays, it is
      unlikely that total elimination will be possible.

PMID- 22618530
TI  - To mix or not to mix in lupus anticoagulant testing? That is the question.
AB  - Mixing patient and normal plasma has been used for many years to assist with
      making decisions on which direction to proceed for further investigation of
      abnormally prolonged coagulation tests, namely, either individual coagulation
      factor measurement or the search for circulating anticoagulants. Mixing tests,
      however, gained wide acceptance only after the so-called lupus-like anticoagulant
      (LA) phenomenon was described and were, therefore, included in the guidelines for
      LA detection issued by the working group of the International Society on
      Thrombosis and Haemostasis. Important though they may be considered, the dispute
      between those who advocate the use of mixing tests and those who deny their
      superiority (or their need) for LA detection is difficult to resolve. This
      article aims to provide a balanced view on this dispute. Based on the limited
      information provided by the literature one may conclude that the disadvantages of
      performing mixing studies are the fact that (1) they are time-consuming; (2) they
      require a suitable source of normal pool plasma; and (3) weak LA may be lost at
      diagnosis due to the dilution of index plasma into normal pooled plasma. On the
      contrary, performing mixing tests makes the occurrence of false-negative LA in
      patients who present with the so-called "lupus cofactor phenomenon" relatively
      unlikely and, therefore, justifies their performance even though the frequency of
      the occurrence of this phenomenon in LA-positive patients is still unknown.

PMID- 22618531
TI  - The future of antiphospholipid antibody testing.
AB  - The presence of antiphospholipid antibodies (aPL) is essential to diagnose the
      antiphospholipid syndrome (APS). Three assays are available to detect the
      presence of these autoantibodies, but all three assays suffer from several
      important drawbacks. First, the assays lack standardization because the results
      of the assay partially depend on the laboratory that performs the assay. Second,
      we do not know whether the assays detect the autoantibody population responsible
      for the clinical manifestations that characterize the syndrome. Finally, the
      assays do not predict the risk of recurrence. There is an absolute need for novel
      assays that generate prognostic information that can be used for a more tailored
      treatment of patients with APS. In 2011, important information became available
      on the protein against which the autoantibodies are directed, beta2-glycoprotein
      I (beta2GPI). Based on the progress we have made in our understanding of the
      physiology of beta2GPI, it should be possible to design assays that can better
      predict the consequences of the presence of aPL in the circulation.

PMID- 22618533
TI  - Non-covalent interactions of coumarin dyes with cucurbit[7]uril macrocycle:
      modulation of ICT to TICT state conversion.
AB  - Non-covalent interaction of coumarin laser dyes, namely coumarin-1 (C1), coumarin
      481 (C481) and coumarin-6H (C6H), with a versatile macrocyclic host molecule
      cucurbit[7]uril (CB7), has been investigated in aqueous solution using
      photophysical methods. Steady-state and time-resolved fluorescence studies
      illustrate significant enhancements/modifications in the fluorescence yields,
      lifetimes and spectral features of C1, C481 and C6H on interaction with CB7, and
      are assigned to 1 : 1 complex formation between the dyes and the CB7 host. The
      complex formation is mainly driven by charge-dipole interaction, as evident from
      the binding constant values (K ~ 10(4)-10(5) M(-1)). The large changes in the
      excited state behaviour of C1 and C481 as compared to C6H in the presence of CB7
      indicate that CB7 binds C1 and C481 through the encapsulation of the 7-N,N'
      diethylamino group of the dyes and the structural rigidity imposed by this
      interaction dramatically alters the excited state properties of the dyes by
      preventing the conversion of their emissive intramolecular charge transfer (ICT)
      state to the non-radiative twisted intramolecular charge transfer (TICT) state.
      The present results direct towards the probable supramolecular approach using
      water soluble macrocyclic CB7, in the development of aqueous dye laser systems in
      the blue-green region.

PMID- 22618532
TI  - N-acetylcysteine protects against hypoxia mimetic-induced autophagy by targeting
      the HIF-1alpha pathway in retinal ganglion cells.
AB  - Hypoxia-induced retinal ganglion cell (RGC) death has been proposed to be the
      critical event in the pathophysiology of glaucoma. Therefore, delaying or halting
      RGC degeneration, known as neuroprotection, is a novel and promising approach
      with potential clinical applications for treating glaucoma. In this study, we
      investigate hypoxia-induced cell death of RGCs and the underlying mechanisms of N
      acetylcysteine (NAC) as a neuroprotectant. To establish a model for chemical
      hypoxia-induced cell death, RGC-5 cells were treated with the hypoxia mimetic
      cobalt chloride (CoCl2). Following CoCl2 exposure, significant levels of
      apoptotic and autophagic cell death were observed in RGC-5 cells, evidenced by
      lysosome dysfunction and autophagosome formation. Pretreating RGC-5 cells with
      NAC significantly counteracted the autophagic cell death. NAC-mediated
      neuroprotection was attributed to the direct scavenging of reactive oxygen
      species and was mediated by targeting the hypoxia-inducible factor-1alpha pathway
      via the BNIP3 and PI3K/Akt/mTOR pathways. These results provide insights into the
      degeneration of RGCs and present a potential clinical application for NAC as a
      neuroprotectant.

PMID- 22618534
TI  - BAIUCAS: a novel BLAST-based algorithm for the identification of upstream open
      reading frames with conserved amino acid sequences and its application to the
      Arabidopsis thaliana genome.
AB  - MOTIVATION: Upstream open reading frames (uORFs) are often found in the 5'
      untranslated regions of eukaryotic messenger RNAs. Some uORFs have been shown to
      encode functional peptides involved in the translational regulation of the
      downstream main ORFs. Comparative genomic approaches have been used in genome
      wide searches for uORFs encoding bioactive peptides, and by comparing uORF
      sequences between a few selected species or among a small group of species, uORFs
      with conserved amino acid sequences (UCASs) have been identified in plants,
      mammals and insects. Regulatory regions within uORF-encoded peptides that are
      involved in translational control are typically 10-20 amino acids long. Detection
      of homology between such short regions largely depends on the selection of
      species for comparison. To maximize the chances of identifying UCASs with short
      conserved regions, we devised a novel algorithm for homology search among a large
      number of species and the automatic selection of uORFs conserved in a wide range
      of species. RESULTS: In this study, we developed the BAIUCAS (BLAST-based
      algorithm for identification of UCASs) method and identified 18 novel Arabidopsis
      uORFs whose amino acid sequences are conserved across diverse eudicot species,
      which include uORFs not found in previous comparative genomic studies due to low
      sequence conservation among species. Therefore, BAIUCAS is a powerful method for
      the identification of UCASs, and it is particularly useful for the detection of
      uORFs with a small number of conserved amino acid residues.

PMID- 22618535
TI  - High-throughput analysis of epistasis in genome-wide association studies with
      BiForce.
AB  - MOTIVATION: Gene-gene interactions (epistasis) are thought to be important in
      shaping complex traits, but they have been under-explored in genome-wide
      association studies (GWAS) due to the computational challenge of enumerating
      billions of single nucleotide polymorphism (SNP) combinations. Fast screening
      tools are needed to make epistasis analysis routinely available in GWAS. RESULTS:
      We present BiForce to support high-throughput analysis of epistasis in GWAS for
      either quantitative or binary disease (case-control) traits. BiForce achieves
      great computational efficiency by using memory efficient data structures, Boolean
      bitwise operations and multithreaded parallelization. It performs a full pair
      wise genome scan to detect interactions involving SNPs with or without
      significant marginal effects using appropriate Bonferroni-corrected significance
      thresholds. We show that BiForce is more powerful and significantly faster than
      published tools for both binary and quantitative traits in a series of
      performance tests on simulated and real datasets. We demonstrate BiForce in
      analysing eight metabolic traits in a GWAS cohort (323 697 SNPs, >4500
      individuals) and two disease traits in another (>340 000 SNPs, >1750 cases and
      1500 controls) on a 32-node computing cluster. BiForce completed analyses of the
      eight metabolic traits within 1 day, identified nine epistatic pairs of SNPs in
      five metabolic traits and 18 SNP pairs in two disease traits. BiForce can make
      the analysis of epistasis a routine exercise in GWAS and thus improve our
      understanding of the role of epistasis in the genetic regulation of complex
      traits. AVAILABILITY AND IMPLEMENTATION: The software is free and can be
      downloaded from http://bioinfo.utu.fi/BiForce/. CONTACT: wenhua.wei@igmm.ed.ac.uk
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 22618536
TI  - SALIGN: a web server for alignment of multiple protein sequences and structures.
AB  - SUMMARY: Accurate alignment of protein sequences and/or structures is crucial for
      many biological analyses, including functional annotation of proteins,
      classifying protein sequences into families, and comparative protein structure
      modeling. Described here is a web interface to SALIGN, the versatile protein
      multiple sequence/structure alignment module of MODELLER. The web server
      automatically determines the best alignment procedure based on the inputs, while
      allowing the user to override default parameter values. Multiple alignments are
      guided by a dendrogram computed from a matrix of all pairwise alignment scores.
      When aligning sequences to structures, SALIGN uses structural environment
      information to place gaps optimally. If two multiple sequence alignments of
      related proteins are input to the server, a profile-profile alignment is
      performed. All features of the server have been previously optimized for
      accuracy, especially in the contexts of comparative modeling and identification
      of interacting protein partners. AVAILABILITY: The SALIGN web server is freely
      accessible to the academic community at http://salilab.org/salign. SALIGN is a
      module of the MODELLER software, also freely available to academic users
      (http://salilab.org/modeller). CONTACT: sali@salilab.org; madhusudhan@bii.a
      star.edu.sg.

PMID- 22618553
TI  - Long-term results after resection arthroplasty in Kienbock's disease.

PMID- 22618552
TI  - Posterior approach for accessory-suprascapular nerve transfer: an
      electrophysiological outcomes study.
AB  - The aim of this study was to retrospectively investigate the electrophysiological
      results obtained after employing the posterior approach for spinal accessory
      nerve-suprascapular nerve (SAN-SSN) transfer, and to compare this with the
      traditional anterior approach. SAN-SSN transfer was performed in 74 patients with
      brachial plexus injury. The posterior approach was used in 35 patients and the
      anterior approach was used in 39 patients. Electrophysiological examination was
      conducted and analyzed postoperatively. There was no significant difference
      between approaches in the time it took for the infraspinatus to show low
      incidence motor unit action potentials (MUAPs) and an incomplete interference
      pattern. In addition, the final ratio of patients that showed regeneration
      potential of the infraspinatus was not significantly different between the
      approaches. Furthermore, latency and wave amplitude showed a linear regression
      with post-operative time in the posterior approach group. In the posterior
      approach group, the final abduction of the shoulder was positively correlated
      with the amplitude. The posterior approach for SAN-SSN is an effective potential
      alternative technique that may be appropriate for some clinical situations.

PMID- 22618554
TI  - Finger injury caused by the surfboard leash while surfing.

PMID- 22618555
TI  - Intraosseous lipoma of the scaphoid.

PMID- 22618556
TI  - The use of Swanson silastic interposition arthroplasty in revision thumb-base
      surgery for failed trapeziectomy; a case series of 10 patients.
AB  - Patients who report ongoing adverse symptoms following trapeziectomy may require
      revision surgery. We present a series of 10 patients who underwent revision
      surgery using a Silastic interpositional finger joint arthroplasty. Mean age was
      60 (range 48-70) years, with a mean interval between primary and revision surgery
      of 34 (range 12-84) months. Review was performed at an average of 53 (range 21
      136) months. Nine of the 10 patients reported improvement in pain, and all
      patients reported improvement in pinch grip, activities of daily living, and
      satisfaction at having undergone revision surgery. There were no complications.
      We found good medium-term results and high satisfaction rates. We advocate this
      technique as an effective treatment option in these difficult cases, provided
      other treatable causes of poor outcome are excluded.

PMID- 22618557
TI  - Spontaneous rupture of the extensor pollicis longus tendon in a patient with
      hyperparathyroidism undergoing chronic haemodialysis.

PMID- 22618558
TI  - Lamb boning -- an occupational cause of carpal tunnel syndrome?
AB  - Whether an occupation can cause carpal tunnel syndrome requiring carpal tunnel
      decompression (CTD) is contentious. We compared the demographics and incidence
      rates in lamb-freezing workers with the general population who had CTD. In the
      general population there were 1002 (63%) females and 583 (37%) males, mean age 48
      years, and the rate of CTD was 1.36/1000 per annum. In lamb-freezing workers
      there were 225 males (mean age 38.4 years) and 60 females (mean age 44.6 years);
      most workers required CTD in their first three seasons. Compared with the general
      population, the incidence rate ratios in all freezing workers was 16.8; boners,
      51.6; meat packers, 22.8; and slaughtermen, 5.4. All groups had a greater rate of
      CTD than the general population. This study suggests that carpal tunnel syndrome
      can be directly caused by an occupation.

PMID- 22618560
TI  - Unrecognized closed mallet thumb injury complicating a closed proximal phalangeal
      fracture of the thumb.

PMID- 22618559
TI  - The relationship between displacement and clinical outcome after distal radius
      (Colles') fracture.
AB  - We reviewed 260 patients who had been treated non-operatively for a dorsally
      displaced distal radius fracture a mean 6.3 (range 2.5-12.7) years earlier, in an
      attempt to find the limits of displacement compatible with a good clinical
      outcome. We excluded patients with previous or later injuries to the same limb.
      Bivariate analysis revealed a highly statistically significant relationship
      between radiographic displacement at review and clinical outcome scores.
      Correlation coefficients varied between 0.14 and 0.30. However, multiple linear
      regression analysis using most factors commonly thought to be of importance in
      determining the clinical outcome as independent variables explained only 23% of
      the variability of the clinical outcome. Dorsal angulation, ulnar variance, and
      radial inclination together accounted for only 11% of the variability. We
      conclude that the final alignment of the distal radius as shown radiologically
      has only a minor influence on the clinical outcome of Colles' type distal radius
      fractures.

PMID- 22618561
TI  - Comparison of the osseous characteristics of medial femoral condyle and fibula
      flaps.

PMID- 22618562
TI  - Number of suture throws and its impact on the biomechanical properties of the
      four-strand cruciate locked flexor tendon repair with FiberWire.
AB  - FiberWire is a popular suture in flexor tendon repair that allows for early
      mobilization, but its poor knot-holding properties have raised concerns over the
      potential effects on tendon healing and strength. We examined how the number of
      knot throws affects the 2 mm gap force, ultimate tensile strength, and mode of
      failure in a four-strand cruciate locked tendon repair in porcine flexor tendons
      in order to elucidate the optimal number of suture throws. There was no effect on
      the 2 mm gap force with increasing knot throws, but there was a significant
      increase in ultimate tensile strength. A minimum of six-knot throws prevents
      unravelling, whereas five out of 10 of repairs unravelled with less than six
      throws.

PMID- 22618563
TI  - The formation of the Hand Club: a 60th anniversary.
AB  - The formation of the Hand Club: a 60th anniversary.

PMID- 22618564
TI  - The results of carpal tunnel release for carpal tunnel syndrome diagnosed on
      clinical grounds, with or without electrophysiological investigations: a
      randomized study.
AB  - We compared the results of carpal tunnel release in patients with the diagnosis
      of carpal tunnel syndrome based on only clinical grounds and those diagnosed on
      clinical and electrophysiological grounds. Ninety-three patients, 83 women (89%)
      and ten men (11%), meeting the criteria of 'typical' carpal tunnel syndrome, were
      randomly assigned to receive carpal tunnel release with (n = 45, 48%) or without
      (n = 48, 52%) nerve conduction studies. Patients were followed-up at 1 and 6
      months, by assessments that included the Levine scores, filament tests, grip and
      pinch strength. No significant differences in Levine scores were found at the 1
      and 6 months assessments. Statistically significant differences were noted in
      three-point pinch strength and sensation; however, they were not of clinical
      importance. The results of the study show that the results of carpal tunnel
      release in patients with typical symptoms are no better after nerve conduction
      studies and, therefore, nerve conduction studies can be omitted.

PMID- 22618565
TI  - Anthrax infection among heroin users in Scotland during 2009-2010: a case-control
      study by linkage to a national drug treatment database.
AB  - Using a data-linkage approach, we conducted a case-control study to investigate
      risk factors in an outbreak of anthrax infection among Scottish heroin users.
      Factors associated with an increased risk of infection included longer injecting
      history, receiving opioid substitution therapy, and alcohol consumption. Smoking
      heroin was associated with lower risk of infection.

PMID- 22618566
TI  - Foodborne toxoplasmosis.
AB  - Toxoplasmosis can be due to congenital infection or acquired infection after
      birth and is one of the leading illnesses associated with foodborne
      hospitalizations and deaths. Undercooked meat, especially pork, lamb, and wild
      game meat, and soil contaminated with cat feces on raw fruits and vegetables are
      the major sources of foodborne transmission for humans. The new trend in the
      production of free-range organically raised meat could increase the risk of
      Toxoplasma gondii contamination of meat. Foodborne transmission can be prevented
      by production practices that reduce T. gondii in meat, adequate cooking of meat,
      washing of raw fruits and vegetables, prevention of cross contamination in the
      kitchen, and measures that decrease spread of viable oocysts into the
      environment.

PMID- 22618567
TI  - Frequent emergence of N348I in HIV-1 subtype C reverse transcriptase with failure
      of initial therapy reduces susceptibility to reverse-transcriptase inhibitors.
AB  - BACKGROUND: It is not known how often mutations in the connection and
      ribonuclease H domains of reverse transcriptase (RT) emerge with failure of first
      line antiretroviral therapy (ART) in subtype C human immunodeficiency virus type
      1 (HIV-1) infection and how these mutations affect susceptibility to other
      antiretrovirals. METHODS: We compared full-length RT sequences in plasma obtained
      before therapy and at virologic failure of initial ART among 63 participants with
      subtype C HIV-1 infection enrolled in the Comprehensive International Program of
      Research on AIDS in South Africa (CIPRA-SA) study. Recombinant viruses containing
      full-length plasma-derived RT sequences from participants with N348I at virologic
      failure were assayed for drug susceptibility. RESULTS: Y181C and M184V mutations
      in the RT polymerase domain were associated with failure of stavudine-lamivudine
      nevirapine (d4T/3TC/NVP; P < .01), and K103N, V106M, and M184V with failure of
      d4T/3TC/efavirenz (EFV; P < .01). N348I in the RT connection domain emerged in
      45% (P = .002) and 12% (P = .06) of participants receiving failing regimens
      containing NVP or EFV, respectively. Longitudinal analyses revealed that
      nonnucleoside RT inhibitor resistance mutations in the polymerase domain
      generally appeared first. N348I emerged at the same time, or after, M184V. N348I
      in the context of polymerase domain mutations reduced susceptibility to NVP (8.9
      13-fold), EFV (4-56-fold), etravirine (ETV; 1.9-4.7-fold) and decreased
      hypersusceptibility to zidovudine (AZT; 1.4-2.2-fold). CONCLUSIONS: N348I emerges
      frequently with virologic failure of first-line ART in subtype C HIV-1 infection
      and reduces susceptibility to NVP, EFV, ETV, and AZT. Additional studies are
      warranted to characterize the effects of N348I on virologic response to second-
      and third-line regimens in resource-limited settings where subtype C
      predominates.

PMID- 22618568
TI  - RNAi of the translation inhibition gene 4E-BP identified from the hard tick,
      Haemaphysalis longicornis, affects lipid storage during the off-host starvation
      period of ticks.
AB  - 4E-BP, an eIF4E-binding protein, is well known as a cap-dependent translation
      inhibitor. Here, the 4E-BP homolog, Hl4E-BP, was isolated and identified from the
      hard tick Haemaphysalis longicornis. Hl4E-BP transcripts were ubiquitously
      expressed in the active stages, including the larvae, nymphs, and female adults,
      and the transcription levels were found to be higher in unfed than engorged
      ticks. In contrast, the expression levels of non-phosphorylated Hl4E-BP, which is
      a 13.4-kDa protein detected by the anti-recombinant Hl4E-BP antibody, were the
      highest in engorged ticks and significantly decreased progressively during the
      unfed starvation period of ticks. The functional role of Hl4E-BP as a metabolic
      brake was verified by histochemical observations on the lipid storage in midguts
      and fat bodies during the starvation period using ticks injected with dsHl4E-BP.
      The results indicate that Hl4E-BP is highly relevant to the lipid storage of
      ticks during the non-feeding starvation period. Our results suggest, for the
      first time, that Hl4E-BP may have a crucial role in the starvation resistance of
      ticks in an off-host condition via lipid metabolism control, although it was
      unclear whether Hl4E-BP might be involved in lipid synthesis regulation and/or
      lipid consumption inhibition.

PMID- 22618570
TI  - Diagnosis and management of hyponatremia in cancer patients.
AB  - Hyponatremia, a common electrolyte abnormality in oncology practice, may be a
      negative prognostic factor in cancer patients based on a systematic analysis of
      published studies. The largest body of evidence comes from small-cell lung cancer
      (SCLC), for which hyponatremia was identified as an independent risk factor for
      poor outcome in six of 13 studies. Hyponatremia in the cancer patient is usually
      caused by the syndrome of inappropriate antidiuretic hormone (SIADH), which
      develops more frequently with SCLC than with other malignancies. SIADH may be
      driven by ectopic production of arginine vasopressin (AVP) by tumors or by
      effects of anticancer and palliative medications on AVP production or action.
      Other factors may cause hypovolemic hyponatremia, including diarrhea and vomiting
      caused by cancer therapy. Hyponatremia may be detected on routine laboratory
      testing before or during cancer treatment or may be suggested by the presence of
      mostly neurological symptoms. Treatment depends on several factors, including
      symptom severity, onset timing, and extracellular volume status. Appropriate
      diagnosis is important because treatment differs by etiology, and choosing the
      wrong approach can worsen the electrolyte abnormality. When hyponatremia is
      caused by SIADH, hypertonic saline is indicated for acute, symptomatic cases,
      whereas fluid restriction is recommended to achieve a slower rate of correction
      for chronic asymptomatic hyponatremia. Pharmacological therapy may be necessary
      when fluid restriction is insufficient. The orally active, selective AVP receptor
      2 (V(2))-receptor antagonist tolvaptan provides a mechanism-based option for
      correcting hyponatremia caused by SIADH or other conditions with inappropriate
      AVP elevations. By blocking AVP effects in the renal collecting duct, tolvaptan
      promotes aquaresis, leading to a controlled increase in serum sodium levels.

PMID- 22618569
TI  - Complementary and alternative medicines in prostate cancer: from bench to
      bedside?
AB  - Complementary and alternative medicine (CAM) use is common among adults, and
      recent reports suggest that 25%-50% of prostate cancer (PCa) patients use at
      least one CAM modality. The most common CAM modalities used by PCa patients are
      vitamin and herbal preparations with purported antitumor effects despite only
      modest underlying preclinical or clinical evidence of efficacy. In this review we
      provide a brief overview of the basic scientific and clinical studies underlying
      the most common herbal and vitamin preparations including common antioxidants,
      pomegranate extract, green tea, turmeric, resveratrol, silibinin, and herbal
      combination preparations. When available, prostate cancer clinical trial data are
      reviewed. Importantly, we have compared the concentration of these agents used in
      in vitro experiments to that likely to be achievable in humans. From the
      available data we conclude that there is insufficient evidence to support the use
      of CAMs for the treatment of prostate cancer patients outside of a clinical
      trial. The purpose of this review is to more rigorously evaluate CAM therapy in
      prostate cancer and educate oncologists and patients. This review focuses on
      examples from the general classes of agents in common use.

PMID- 22618572
TI  - A full dimensional grid empowered simulation of the CO2 + CO2 processes.
AB  - A recently introduced bond-bond formulation of the intermolecular interaction has
      been extended to six-atom systems to the end of assembling a new potential energy
      surface (PES) and has been incorporated into a grid empowered simulator able to
      handle the modeling of the CO(2) + CO(2) processes. The proposed PES is full
      dimensional and accounts for the dependence of the intermolecular interaction on
      some basic physical properties of the colliding partners, including modulations
      induced by the monomer deformation. The used analytical formulation of the
      interaction involves a limited number of parameters, each having a clear physical
      meaning. Guess values for these parameters can also be obtained from analytical
      correlation formulae. Such estimates can then be fine tuned by exploiting
      experimental and theoretical information. The resulting PES well describes
      stretched and bent asymptotic CO(2) monomers as well as the CO(2)-CO(2)
      interaction in the most and less stable configurations. On this potential massive
      quasiclassical elastic and inelastic detailed scattering trajectories have been
      integrated, by exploiting the innovative computational technologies of the grid.
      The efficiency of the approach used and the reliability of the estimates of the
      dynamical properties obtained in this way is such that we can now plan a
      systematic evaluation of the state specific rate coefficient matrix elements
      needed for space craft reentry modeling. Here, we present probabilities and cross
      sections useful to rationalize some typical mechanisms characterizing the
      vibrational transitions of the CO(2) + CO(2) system on the flexible monomer
      proposed PES. On such PES, the key dynamical outcomes are: (a) there is a strong
      energy interchange between symmetric stretching of the reactants and bending of
      the products (and viceversa) while asymmetric stretching is strongly adiabatic
      (b) reactant energy is more efficiently allocated (with respect to the rigid
      monomers PES) as product vibration when reactant stretching modes are excited
      while the contrary is true when the reactant bending mode is excited.

PMID- 22618571
TI  - A second-generation microRNA-based assay for diagnosing tumor tissue origin.
AB  - BACKGROUND: Cancers of unknown primary origin (CUP) constitute 3%-5% (50,000 to
      70,000 cases) of all newly diagnosed cancers per year in the United States.
      Including cancers of uncertain primary origin, the total number increases to 12%
      15% (180,000 to 220,000 cases) of all newly diagnosed cancers per year in the
      United States. Cancers of unknown/uncertain primary origins present major
      diagnostic and clinical challenges because the tumor tissue of origin is crucial
      for selecting optimal treatment. MicroRNAs are a family of noncoding, regulatory
      RNA genes involved in carcinogenesis. MicroRNAs that are highly stable in
      clinical samples and tissue specific serve as ideal biomarkers for cancer
      diagnosis. Our first-generation assay identified the tumor of origin based on 48
      microRNAs measured on a quantitative real-time polymerase chain reaction platform
      and differentiated 25 tumor types. METHODS: We present here the development and
      validation of a second-generation assay that identifies 42 tumor types using a
      custom microarray. A combination of a binary decision-tree and a k-nearest
      neighbor classifier was developed to identify the tumor of origin based on the
      expression of 64 microRNAs. RESULTS: Overall assay sensitivity (positive
      agreement), measured blindly on a validation set of 509 independent samples, was
      85%. The sensitivity reached 90% for cases in which the assay reported a single
      answer (>80% of cases). A clinical validation study on 52 true CUP patients
      showed 88% concordance with the clinicopathological evaluation of the patients.
      CONCLUSION: The abilities of the assay to identify 42 tumor types with high
      accuracy and to maintain the same performance in samples from patients clinically
      diagnosed with CUP promise improved utility in the diagnosis of cancers of
      unknown/uncertain primary origins.

PMID- 22618573
TI  - Planar P(6)E(6) (E = Se, S) macrocycles incorporating P(2)N(2) scaffolds.
AB  - Oxidation of alkali metal derivatives of the dianions [E((t)BuN)P(MU
      N(t)Bu)(2)P(N(t)Bu)E](2-) (E = S, Se) with I(2) produces 15-membered macrocycles
      in which a planar P(6)E(6) motif is stabilised by perpendicular P(2)N(2)
      scaffolds.

PMID- 22618574
TI  - Metabolomics-on-a-chip and metabolic flux analysis for label-free modeling of the
      internal metabolism of HepG2/C3A cells.
AB  - In vitro microfluidic systems are increasingly used as an alternative to standard
      Petri dishes in bioengineering and metabolomic investigations, as they are
      expected to provide cellular environments close to the in vivo conditions. In
      this work, we combined the recently developed "metabolomics-on-a-chip" approach
      with metabolic flux analysis to model the metabolic network of the hepatoma
      HepG2/C3A cell line and to infer the distribution of intracellular metabolic
      fluxes in standard Petri dishes and microfluidic biochips. A high pyruvate
      reduction to lactate was observed in both systems, suggesting that the cells
      operate in oxygen-limited environments. Our results also indicate that HepG2/C3A
      cells in the biochip are characterized by a higher consumption rate of oxygen,
      presumably due to a higher oxygenation rate in the microfluidic environment. This
      leads to a higher entry of the ultimate glycolytic product, acetyl-CoA, into the
      Krebs cycle. These findings are supported by the transcriptional activity of
      HepG2/C3A cells in both systems since we observed that genes regulated by a HIF-1
      (hypoxia-regulated factor-1) transcriptional factor were over expressed under the
      Petri conditions, but to a lesser extent in the biochip.

PMID- 22618576
TI  - Tracheal aspiration of capsule endoscopes: detection, management, and
      susceptibility.

PMID- 22618575
TI  - Dismembered and non-dismembered retroperitoneoscopic pyeloplasty for the
      treatment of ureteropelvic junction obstruction in children.
AB  - PURPOSE: Open dismembered pyeloplasty according to Anderson-Hynes (AHP) is the
      gold standard treatment for ureteropelvic junction obstruction in children.
      However, during the last decade, the management has been revolutionized with
      introduction of laparoscopy and endourology yielding comparable results and less
      morbid outcomes. METHODS: Between 1997 and 2010, dismembered and non-dismembered
      retroperitoneoscopic pyeloplasty was performed in 41 children with a median age
      of 130 month (range 5-192). 20 children underwent a dismembered pyeloplasty
      (Anderson-Hynes) and 21 children were operated by a non-dismembered pyeloplasty
      (Y-V-Plasty). RESULTS: The mean operation time was 120 min (range 52-257).
      Intraoperative findings revealed in 29 cases a significant crossing vessel. Based
      on a furosemide nephrogram and subjective complaints, the success rate was 88 %
      with a median follow-up of 69 month (range 14-142). The 5 failures (2 Y-V-Plasty,
      3 AHP) have been treated by open AHP (n = 2), Laser endopyelotomy (n = 2) and Lap
      AHP (n = 1) without further problems. CONCLUSION: With increasing improvement of
      the suture techniques, the laparoscopic pyeloplasty represents in experienced
      hands an alternative method with comparable success rates to the open technique.
      In our opinion, retroperitoneoscopic pyeloplasty is technically possible and
      feasible even in infants. We found in our series no statistically significant
      difference between dismembered and non-dismembered pyeloplasty.

PMID- 22618577
TI  - Expression of Toll-like receptors in enterocromaffin-like cells and their
      function in histamine release.
AB  - INTRODUCTION: Enterocromaffin-like cells (ECL) are specialized endocrine gastric
      cells able to release histamine, which in turn controls gastric acid production
      by parietal cells. Helicobacter pylori infection and other conditions signal in
      the gastrointestinal tract via Toll-like receptors (TLRs) and modify gastric acid
      production, but there is no evidence of expression and function of TLRs in ECL
      cells. In this work, we analyzed gene and protein expression of TLR-2, 4, 5, and
      9, and other molecules involved in TLR signaling in ECL cells. MATERIAL AND
      METHODS: ECL cells were isolated from Sprague-Dawley rats. The histamine
      releasing ability of TLR ligands was also evaluated after culture of the ECL
      cells for a short time. RESULTS: With ECL cells that expressed the TLR-2, TLR-4,
      TLR-5, and TLR-9 genes we were able to confirm protein expression for TLR-2, TLR
      5, and TLR-9. Functionally, ECL cells were able to release histamine in response
      to TLR-2 stimulation by peptidoglycan (PGN), a TLR-2 ligand. After PGN stimulus,
      IRAK and p38 phosphorylation could be observed. SB 203580, a p38 inhibitor,
      reversed PGN-induced histamine release. Lipopolysaccharide (LPS), a TLR-4 ligand,
      was also able to induce histamine release in ECL cells, but by a mechanism
      independent of TLRs. CONCLUSIONS: We have demonstrated for the first time that
      ECL cells express TLRs and respond to TLR-2 ligand by increasing histamine
      release. This response could be involved in host defense against gastrointestinal
      bacterial pathogens but could also contribute to control of gastric acid
      secretion in the absence of pathogens.

PMID- 22618578
TI  - [Stent for reduction of pancreatic fistula after pancreaticojejunostomy. No
      indication for routine stenting].

PMID- 22618579
TI  - [Subtotal adrenalectomy due to MEN2 pheochromocytoma].

PMID- 22618580
TI  - [Short-term outcome after open and minimally invasive esophagus resection of
      carcinomas. A retrospektive study from England].

PMID- 22618581
TI  - Shared decision making: a model for clinical practice.
AB  - The principles of shared decision making are well documented but there is a lack
      of guidance about how to accomplish the approach in routine clinical practice.
      Our aim here is to translate existing conceptual descriptions into a three-step
      model that is practical, easy to remember, and can act as a guide to skill
      development. Achieving shared decision making depends on building a good
      relationship in the clinical encounter so that information is shared and patients
      are supported to deliberate and express their preferences and views during the
      decision making process. To accomplish these tasks, we propose a model of how to
      do shared decision making that is based on choice, option and decision talk. The
      model has three steps: a) introducing choice, b) describing options, often by
      integrating the use of patient decision support, and c) helping patients explore
      preferences and make decisions. This model rests on supporting a process of
      deliberation, and on understanding that decisions should be influenced by
      exploring and respecting "what matters most" to patients as individuals, and that
      this exploration in turn depends on them developing informed preferences.

PMID- 22618582
TI  - Evaluation of the effectiveness of making Weight Watchers available to Tennessee
      Medicaid (TennCare) recipients.
AB  - INTRODUCTION: In 2006, Tennessee Medicaid (TennCare) offered its recipients
      access to Weight Watchers for a nominal fee. The aim of this study was to
      determine the weight change among adult participants. METHODS: This is a
      retrospective analysis of weight change among overweight and obese TennCare
      recipients who participated in the program. Weight change was calculated as the
      median difference from the first date of participation to the last. Weight change
      was also calculated as median percentage change from initial weight and
      categorized as weight loss or gain of 0 to 5, >=5 to 10, and >=10 %. RESULTS:
      During the study period, 1,605 individuals started the program and 1192 had at
      least one follow-up weight measurement and thus met the inclusion criteria for
      the study. Women (n = 1149) had a BMI of 39.6 kg/m(2) and men (n = 43) had a BMI
      of 43.0 kg/m(2). The median weight loss for all participants was 1.9 kg, or 1.8 %
      of initial weight. Twenty percent of participants lost 5 % or more of their
      initial body weight while participating in the program. Over 13 % of participants
      only attended two meetings; on average, these participants lost 0.5 % of initial
      weight. Over 23 % of participants attended 13 or more meetings, and they lost an
      average of 6.4 % of initial weight. DISCUSSION: Twenty percent of TennCare
      recipients who joined Weight Watchers lost a clinically significant amount of
      weight. Participants who attended more meetings lost more weight. Reimbursement
      for Weight Watchers has been maintained by all of the Medicaid managed care
      organizations in Tennessee. Partnerships that allow low-income populations to
      access weight loss programs may provide a valuable weight management tool.

PMID- 22618583
TI  - Patent ductus arteriosus aneurysm: a rare cause of dyspnea in an adolescent boy.
AB  - We report a rare cause of dyspnea in an adolescent boy who presented with
      complaints of dyspnea on exertion since childhood without any cyanosis. Computed
      tomography angiography showed a large patent ductus arteriosus aneurysm that was
      seen compressing on the trachea and a left main bronchus with associated
      decreased left lung volume.

PMID- 22618584
TI  - Prenatal diagnosis of hypoplastic left heart syndrome: impact of counseling
      patterns on parental perceptions and decisions regarding termination of
      pregnancy.
AB  - An online survey for parents of children with congenital heart disease (CHD) was
      developed to study parents' experiences at the time of diagnosis. The survey was
      distributed to online support groups. A total of 841 responses from parents of
      children with CHD were received during a 4-week period. The current study
      examined those respondents (211 [25 %]) who reported their child's diagnosis as
      hypoplastic left heart syndrome (HLHS). Among these, 138 (65 %) reported
      receiving the diagnosis prenatally. 32 % of those receiving a prenatal diagnosis
      reported that after they declined to terminate the pregnancy, termination was
      mentioned again by their physicians. Parents who had termination mentioned again
      after their initial decline reported significantly lower optimism regarding their
      child's life expectancy than those who did not have it mentioned again (66 vs. 94
      %, p < 0.001); were more likely to interpret the term "rare" to mean "little or
      no chance of survival" (34 vs. 13 %, p = 0.01); and were more likely to change
      pediatric cardiologists (PCs) (43 vs. 12 %, p < 0.001). Similarly, 22 % of
      respondents receiving a prenatal diagnosis reported feeling pressure to terminate
      the pregnancy by the PC. Those who felt pressure to terminate reported lower
      optimism about their child's life expectancy than respondents who did not feel
      pressure (48 vs. 88 %, p < 0.001) and were more likely to choose a new PC (48 vs.
      17 %, p < 0.001). In our cohort of parents, when termination of pregnancy was
      mentioned after the parents declined it, or if the parents felt pressure to
      terminate, the parents perceived a lower chance of survival, felt less optimistic
      about their child's life expectancy, and were more likely to choose another PC
      for long-term follow-up care. Our study could not determine whether repeated
      discussions of the possibility for termination of pregnancy independently impacts
      parental optimism regarding prognosis or whether those who counsel with repeated
      discussions of termination tend to have more guarded notions of the prognosis of
      children with HLHS. Further study is warranted to identify the implications of
      counseling patterns on parental perceptions and decisions regarding termination
      of pregnancy.

PMID- 22618585
TI  - Symptomatic upper-extremity deep venous thrombosis after pacemaker placement in a
      pediatric patient: how to treat?
AB  - Symptomatic upper-extremity deep venous thrombosis (UEDVT) after pacemaker
      placement in adults has been reported, but the occurrence of UEDVT in pediatric
      patients is poorly defined, and no treatment guidelines exist. This report
      describes a 14-year old girl with a history of complete atrioventricular block
      who experienced a symptomatic UEDVT 8 months after placement of a transvenous
      pacemaker. The girl was treated initially with anticoagulation including
      subcutaneous enoxaparin and a heparin drip, which did not resolve the venous
      obstruction. In the interventional laboratory, a venogram demonstrated complete
      obstruction of the left subclavian vein, which was treated successfully with
      catheter-directed alteplase, direct thrombus removal by manual suctioning, and
      balloon angioplasty. Warfarin therapy was continued for an additional 6 months,
      with follow-up venous ultrasounds demonstrating left subclavian vein patency.
      Soon after completing warfarin therapy, the girl presented with minimal edema of
      her left distal extremity and was thought to have post-thrombotic syndrome, which
      resolved quickly. She continued to receive aspirin therapy, with no recurrence of
      symptoms. In conclusion, symptomatic UEDVT after pacemaker placement in a
      pediatric patient can be treated successfully with both anticoagulation and
      interventional therapies. Further studies are needed to evaluate the incidence of
      thrombus formation among children with transvenous pacemaker placement together
      with the development of guidelines based on the safety and effectiveness of
      differing treatments.

PMID- 22618586
TI  - Regional reduction in gray and white matter volume in brains of cirrhotic
      patients: voxel-based analysis of MRI.
AB  - Chronic hepatic encephalopathy is a characteristically reversible
      neuropsychiatric disorder that occurs mainly in patients with liver cirrhosis.
      The brain regions critically involved in the pathophysiology of cirrhosis are not
      clear. Magnetic resonance imaging (MRI) with voxel-based morphometry (VBM) is a
      valuable tool for evaluating structural brain changes in many neurodegenerative
      diseases. We performed an MRI scan on 18 patients with liver cirrhosis and 16 age
      matched healthy controls. We evaluated brain regional structural changes,
      regional differences and the relationship of these changes with the blood levels
      of ammonia and the results of neuropsychological tests in patients with
      cirrhosis. The VBM showed reduction in the volume of gray matter in the
      cerebellum and occipital lobe and in the volume of white matter in the cingulate,
      parietal, temporal, occipital lobe and precentral area in cirrhotic patients
      compared with controls. There were significant correlations between the volume of
      these regions with the plasma levels of ammonia and the results of
      neuropsychological tests. Voxel-based analysis of MRI revealed evidence for
      structural abnormalities of brain in patients with cirrhosis. Abnormal function
      in the above regions may account for the ammonia-mediated changes and
      neuropsychological deficits in hepatic encephalopathy.

PMID- 22618588
TI  - The effects of peripapillary atrophy on the diagnostic ability of Stratus and
      Cirrus OCT in the analysis of optic nerve head parameters and disc size.
AB  - PURPOSE: We compared the diagnostic ability of Stratus and Cirrus optical
      coherence tomography (OCT) in optic nerve head (ONH) analysis, and examined the
      effects of optic disc size and peripapillary atrophy (PPA) on their diagnostic
      capacity. METHODS: Stratus and Cirrus OCT was performed in 28 control and 78
      glaucomatous eyes. ONH parameters and diagnostic capacity calculated from the
      area under the receiver operating characteristics curve (AUC) were compared
      between the two modalities. Glaucomatous eyes were classified by optic disc size
      and the presence/absence of PPA, and their AUCs were compared. RESULTS: Rim area
      (AUC 0.936) and rim volume (AUC 0.824) showed the best diagnostic capacity in
      Cirrus and Stratus OCT, respectively. Cirrus OCT showed greater diagnostic
      ability over Stratus OCT for all ONH parameters. With increasing ONH size,
      diagnostic ability declined in rim and disc areas, while it improved in average
      cup-to-disc ratio (CDR), vertical CDR, and cup volume for both modalities. Optic
      disc size as measured by Stratus OCT was significantly larger than that by Cirrus
      OCT in glaucomatous eyes with PPA. In addition, the diagnostic capacity of all
      ONH parameters declined significantly for glaucomatous eyes with PPA, especially
      for Stratus OCT. In Cirrus OCT, retinal nerve fiber layer (RNFL) thickness showed
      poorer diagnostic ability than rim area in the glaucoma with PPA group.
      CONCLUSIONS: The diagnostic capacity of Cirrus OCT was superior to that of
      Stratus OCT. Considering the principle of determining the disc margin, as Stratus
      OCT tends to make excessive measurements of the optic disc in PPA, caution is
      required in analyzing the results.

PMID- 22618587
TI  - Intrastriatal B-cell administration limits infarct size after stroke in B-cell
      deficient mice.
AB  - Recent evidence emphasizes B-cells as a major regulatory cell type that plays an
      important role in limiting the pathogenic effects of ischemic stroke. The aim of
      the current study was to extend this initial observation to specifically examine
      the infiltration of regulatory B-cells and to determine if the effect of B-cells
      to limit the inflammatory response to cerebral ischemia is mediated by their
      action centrally or peripherally. Our data demonstrate the increased presence of
      a regulatory B-cell subset in the affected hemisphere of wild-type mice after
      middle cerebral artery occlusion (MCAO). We further explored the use of a novel
      method of stereotaxic cell delivery to bypass the blood brain barrier (BBB) and
      introduce CD19(+) B-cells directly into the striatum as compared to peripheral
      administration of B-cells. Infarct volumes after 60 minutes of MCAO and 48 hours
      of reperfusion were determined in B-cell deficient MUMT( -/- ) mice with and
      without replacement of either B-cells or medium. Infarct size was significantly
      decreased in cerebral cortex after intrastriatal transfer of 100,000 B-cells to
      MUMT(-/-) mice vs. controls, with a comparable effect on infarct size as obtained
      by 50 million B-cells transferred intraperitoneally. These findings support the
      hypothesis that B-cells play a protective role against ischemic brain injury, and
      suggest that B-cells may serve as a novel therapeutic agent for modulating the
      immune response in central nervous system inflammation after stroke.

PMID- 22618589
TI  - Monitoring morphological changes in the retina of rhodopsin-/- mice with spectral
      domain optical coherence tomography.
AB  - PURPOSE: The rhodopsin(-/-) C57Bl/6 (rho(-/-)) mouse is a very important model
      for understanding retinal degenerative diseases. In this study, spectral domain
      optical coherence tomography (SD-OCT) was used to monitor the dynamic
      morphological changes in retina of rho(-/-) mice. METHODS: Rho(-/-) mice and wild
      type C57Bl/6 (B6) mice at the age of 3, 6, 9, and 12 weeks were investigated
      using SD-OCT to obtain cross-sectional images of the retina. The outer nuclear
      layer (ONL) thickness was measured. Histological sections were used to compare to
      the OCT data. Electroretinograms (ERG) were performed to evaluate the
      physiological change for establishing the relationship between retinal morphology
      and its functional changes. RESULTS: There was no apparent morphological or
      functional change in B6 mice at any time point. The SD-OCT measurement showed
      that the ONL thickness in rho(-/-) mice was significantly decreased from 40.6 MUm
      to 6.0 MUm from week 3 to week 12 postnatal. Histological examinations identified
      a similar trend, although the average thickness of ONL from histological sections
      at these time points was slightly larger (ranging from 55.4 MUm to 14.9 MUm). The
      ERG in rho(-/-) mice indicated functional changes that were in concordant with
      morphological changes; a significant linear positive association was identified
      between the amplitude of b-wave and the ONL thickness. CONCLUSIONS: Our findings
      confirmed that the functional changes in retina were concordant with
      morphological changes measured by SD-OCT in vivo, which indicates that SD-OCT can
      be used as a reliable noninvasive method to monitor the degenerative progression
      in retinal disease models.

PMID- 22618590
TI  - MMP2 activity is critical for TGFbeta2-induced matrix contraction--implications
      for fibrosis.
AB  - PURPOSE: The fibrotic lens disorder posterior capsule opacification (PCO)
      develops in millions of patients following cataract surgery. PCO characteristics
      are extensive extracellular matrix (ECM) production and contraction of the
      posterior lens capsule, resulting in light-scattering ECM modification
      (wrinkling). The pro-fibrotic cytokine transforming growth factor beta (TGFbeta)
      is central to PCO development. This study aimed to elucidate the role of the ECM
      modulators matrix metalloproteinases (MMPs) in TGFbeta-mediated PCO formation.
      METHODS: The human lens epithelial cell-line FHL-124 and human capsular bag
      models were employed. Gene expression of MMP family members was determined by
      oligonucleotide microarray and quantitative real-time RT-PCR. MMP2 and MT1-MMP
      protein levels were analyzed by ELISA and Western blotting, respectively. Matrix
      contraction was determined using an FHL-124 patch contraction assay; at end
      point, cells were stained with Coomassie brilliant blue and area was determined
      using image analysis software. Cell coverage and wrinkle formation on the
      posterior capsule were also assessed using human capsular bag models. RESULTS:
      Active TGFbeta2 (10 ng/mL) increased gene and protein levels of MMP2 and MT1-MMP
      and induced matrix contraction in FHL-124 cells. Specific siRNA inhibition of MT1
      MMP did not suppress TGFbeta2-induced matrix contraction. Active TGFbeta2
      mediated contraction was prevented by broad-spectrum MMP inhibitor GM6001 (25
      MUM), MMP2 siRNA, and MMP2 neutralizing antibody (4 MUg/mL). TGFbeta2-induced
      wrinkle formation was attenuated in human capsular bags treated with MMP2
      neutralizing antibody (20 MUg/mL). CONCLUSIONS: MMP2 plays a critical role in
      TGFbeta2-mediated matrix contraction, which appears to be independent of MT1-MMP.
      MMP2 inhibition provides a novel strategy for the treatment of PCO and
      potentially other fibrotic disorders.

PMID- 22618591
TI  - Focal macular electroretinograms after intravitreal injections of bevacizumab for
      age-related macular degeneration.
AB  - PURPOSE: To evaluate the changes in the best-corrected visual acuity (BCVA),
      macular thickness, and focal macular electroretinograms (FMERGs) after three
      intravitreal injections of bevacizumab for a choroidal neovascularization (CNV)
      associated with age-related macular degeneration (AMD). METHODS: The medical
      records of 18 eyes of 18 patients who had received three consecutive monthly
      intravitreal injections of bevacizumab were retrospectively studied. The BCVA,
      macular thickness determined by optical coherence tomography (OCT), and FMERGs
      were measured before the first injection, and 10 days after each of the
      intravitreal bevacizumab injections. RESULTS: The number of eyes with improvement
      in BCVA after the first injection was one (6%), after the second injection was
      four (22%), and after the third injection was five (28%). The number of eyes with
      reduction in macular thickness was 4 (33%), 8 (44%), and 10 (56%) after each of
      the three injections. The number of eyes with increase in b-wave amplitude of the
      FMERGs was 7 (38%), 6 (33%), and 10 (56%) after each of the three each
      injections. The mean macular thickness was significantly thinner after the first
      injection, and the mean BCVA was significantly improved after the second
      injection. The mean amplitude and implicit time of the b-wave of the FMERGs were
      significantly improved only after the third injection (P<0.05). CONCLUSIONS: All
      parameters improved but the best was after the third injection, indicating that
      three monthly intravitreous injections with bevacizumab may be an effective
      treatment regimen for AMD.

PMID- 22618592
TI  - Association of genetic polymorphisms and age-related macular degeneration in
      Chinese population.
AB  - PURPOSE: We explored associations between age-related macular degeneration (AMD)
      and genetic variants of 10 genes in a nationwide Chinese population. METHODS: In
      this multicenter case-control study, 535 AMD patients and 469 controls were
      recruited from 16 centers that spread from the north to the south of China. All
      participants underwent comprehensive eye examinations, and 40 single nucleotide
      polymorphisms (SNPs) of 10 genes were selected. DNA samples were genotyped with
      the MassArray system. The effect of the genotypes and haplotypes on AMD was
      assessed with logistic regression analysis, adjusted for age, sex, long-term
      residence, and family origin. RESULTS: In our study, 11 SNPs in complement H
      (CFH), 2 in age-related maculopathy susceptibility 2 (ARMS2), and 2 in high
      temperature requirement factor A1 (HTRA1) were associated significantly with AMD.
      They were rs551397, rs800292, rs1329424, rs1061170, rs10801555, rs12124794,
      rs10733086, rs10737680, rs2274700, rs1410996, and rs380390 in CFH; rs10490924 and
      rs2736912 in ARMS2; and rs11200638 and rs3793917 in HTRA1. Three haplotypes in
      CFH, predisposed the patients significantly to AMD (P<0.001, P=0.001, and
      P<0.001, respectively). With the sample size of our study, no relationship was
      found for AMD and the SNPs tested in complement 3 (C3); serpin peptidase
      inhibitor, clade G, member 1 (SERPING1); vascular endothelial growth factor
      (VEGF); cholesterol ester transfer protein (CETP); lipoprotein lipase (LPL);
      hepatic lipase (LIPC); and metallopeptidase inhibitor 3 (TIMP3) genes.
      CONCLUSIONS: Gene variants in CFH, ARMS2, and HTRA1 contribute to AMD in the
      Chinese population.

PMID- 22618593
TI  - Patients with central visual field loss adopt a cautious gait strategy during
      tasks that present a high risk of falling.
AB  - PURPOSE: To investigate how patients with central visual field loss (CFL)
      complete adaptive gait tasks when compared to visual normals and determine
      whether task difficulty significantly affects movement control. METHODS: Ten
      patients with CFL and 12 visual normals negotiated a floor-based obstacle (of
      different heights, 5 and 10 cm) and also walked across an unobstructed laboratory
      (no obstacle present). Analysis assessed the kinematics of human movement for
      each task. RESULTS: During obstacle crossing, compared to visual normals,
      patients with CFL lifted their lead and trail foot significantly higher to avoid
      the obstacle, reduced horizontal crossing velocity (only significant at low
      obstacle height), and increased head flexion to look down at more immediate areas
      of the ground (P < 0.05). During the walking only trials there was no significant
      difference between the two groups in any of the kinematic measures. CONCLUSIONS;
      Compared to visual normals, patients with CFL adopt a cautious gait strategy
      during tasks that present a high risk of falling, such as obstacle crossing.
      However, under conditions that present a low risk of tripping or falling, such as
      level walking, differences appear minimal.

PMID- 22618594
TI  - Biometric evaluation of anterior chamber changes after physiologic pupil dilation
      using Pentacam and anterior segment optical coherence tomography.
AB  - PURPOSE: We evaluated changes in anterior chamber (AC) morphology and iris volume
      induced by physiological mydriasis in fellow eyes of acute angle-closure
      patients, and age-, sex-, and central AC depth-matched primary angle-closure
      suspects (PACS). METHODS: In our study, 21 fellow eyes of patients with acute
      angle closure; 40 age-, sex-, and central AC depth-matched PACS eyes; and 40 age-
      and sex-matched normal open-angle eyes were imaged using a Pentacam and anterior
      segment optical coherence tomography (AS-OCT) under light conditions, and after 5
      minutes of darkness using AS-OCT. Iris volume was estimated using AS-OCT and a
      customized image-processing software. RESULTS: Central AC depth, corneal
      curvature, axial length, and lens thickness did not differ significantly between
      the PACS and fellow eyes. When going from light to dark, angle opening distance
      at 500 MUm decreased significantly more in fellow eyes than in PACS (-68% vs. 
      52%, P < 0.001). When going from light to dark, the mean iris volume increased
      significantly in the fellow eyes (from 45.34 +/- 2.1 to 47.68 +/- 3.2 mm(3), P <
      0.01), whereas it decreased significantly in most PACS eyes (from 45.01 +/- 2.2
      to 42.11 +/- 2.3 mm(3), P < 0.01), and in all open-angle eyes (from 44.68 +/-
      1.16 to 41.67 +/- 1.20 mm(3), P < 0.01). Based on multivariate analysis,
      significant predictors of angle narrowing under darkness (relative change in
      angle-opening distance 500) were fellow eyes compared to PACS (beta = -2.98, SE =
      0.249, P = 0.005) and higher iris volume increase with pupil dilation (beta = 
      3.146, SE = 0.432, P = 0.015). CONCLUSIONS: Under dark conditions, angles of
      fellow eyes closed dramatically more than did those of PACS. Iris volume increase
      per millimeter of pupil dilation is an independent predictor of angle narrowing
      in darkness.

PMID- 22618595
TI  - Soluble vascular adhesion protein-1 accumulates in proliferative diabetic
      retinopathy.
AB  - PURPOSE: Vascular adhesion protein (VAP)-1, a multifunctional molecule with
      adhesive and enzymatic properties, is expressed at the surface of vascular
      endothelial cells of mammals. It also exists as a soluble form (sVAP-1), which is
      implicated in oxidative stress via its enzymatic activity. This study explores a
      link between increased level of sVAP-1 and oxidative stress in proliferative
      diabetic retinopathy (PDR) with a focus on mechanistic components to form sVAP-1
      by shedding from retinal endothelial cells. METHODS: Protein levels of sVAP-1 and
      N epsilon-(hexanoyl)lysine (HEL), an oxidative stress marker, in the vitreous
      samples from patients with PDR or non-PDR were measured by ELISA. The mechanism
      of VAP-1 shedding under diabetic condition, exposure to high glucose and/or
      inflammatory cytokines, was explored using cultured retinal capillary endothelial
      cells. RESULTS: Protein level of sVAP-1 was increased and correlated with HEL in
      the vitreous fluid of patients with PDR. Retinal capillary endothelial cells
      released sVAP-1 when stimulated with high glucose or inflammatory cytokines, such
      as TNF-alpha and IL-1beta in vitro. Furthermore, matrix metalloproteinase-2 and 
      9, type IV collagenases, were the key molecules to mediate the protein cleavage
      of VAP-1 from retinal capillary endothelial cells. CONCLUSIONS: Our data for the
      first time provide evidence on the link between sVAP-1 and type IV collagenases
      in the pathogenesis of PDR.

PMID- 22618597
TI  - The importance of rating scale design in the measurement of patient-reported
      outcomes using questionnaires or item banks.
AB  - PURPOSE: To investigate the effect of rating scale designs (question formats and
      response categories) on item difficulty calibrations and assess the impact that
      rating scale differences have on overall vision-related activity limitation
      (VRAL) scores. METHODS: Sixteen existing patient-reported outcome instruments
      (PROs) suitable for cataract assessment, with different rating scales, were self
      administered by patients on a cataract surgery waiting list. A total of 226 VRAL
      items from these PROs in their native rating scales were included in an item bank
      and calibrated using Rasch analysis. Fifteen item/content areas (e.g., reading
      newspapers) appearing in at least three different PROs were identified. Within
      each content area, item calibrations were compared and their range calculated.
      Similarly, five PROs having at least three items in common with the Visual
      Function (VF-14) were compared in terms of average item measures. RESULTS: A
      total of 614 patients (mean age +/- SD, 74.1 +/- 9.4 years) participated. Items
      with the same content varied in their calibration by as much as two logits;
      "reading the small print" had the largest range (1.99 logits) followed by
      "watching TV" (1.60). Compared with the VF-14 (0.00 logits), the rating scale of
      the Visual Disability Assessment (1.13 logits) produced the most difficult items
      and the Cataract Symptom Scale (0.24 logits) produced the least difficult items.
      The VRAL item bank was suboptimally targeted to the ability level of the
      participants (2.00 logits). CONCLUSIONS: Rating scale designs have a significant
      effect on item calibrations. Therefore, constructing item banks from existing
      items in their native formats carries risks to face validity and transmission of
      problems inherent in existing instruments, such as poor targeting.

PMID- 22618596
TI  - New proteins as vascular biomarkers in primary open angle glaucomatous aqueous
      humor.
AB  - PURPOSE: The aim of this study was to investigate the expression level of several
      biomarkers in the in the aqueous humor of 14 patients with primary open angle
      glaucoma who underwent glaucoma surgery, and 11 nonglaucomatous normals who
      underwent cataract extraction surgery. METHODS: The aqueous humor proteome of 25
      patients was analyzed using an antibody microarray. Fourteen patients with
      uncontrolled intraocular pressure-despite profound therapeutic interventions-who
      underwent filtering procedures and 11 control subjects who underwent surgery for
      senile cataracts were included in the present study. Protein expression was
      evaluated using Cy3/Cy5 labeling, column purification, and hybridization on
      antibody-spotted glass microarrays. Fluorescent signals were detected by
      fluorescence laser scanning. RESULTS: The levels of 13 proteins were
      significantly increased in the aqueous humor of glaucomatous patients compared
      with expression levels in healthy controls. One of the 13 proteins (ELAM 1) was
      involved in inflammation. Two of these proteins (apolipoprotein B and E) were
      involved in the delivery of cholesterol to cells. Five of the 13 proteins
      (myotrophin, myoblast determination protein 1, myogenin, vasodilator-stimulated
      phosphoprotein, and ankyrin-2) were involved in muscle cell differentiation and
      function. Three proteins (heat shock 60 kilodaltons (kDa) and 90 kDa proteins,
      and ubiquitin fusion degradation 1-like) were involved in stress response and the
      removal of damaged proteins; and two proteins (phospholipase C beta and gamma)
      were involved in signal transduction and neural development. CONCLUSIONS: The
      expressions of these proteins in the aqueous humor of glaucomatous patients
      reflect the damage occurring in anterior chamber endothelia, mainly including the
      trabecular meshwork, which is the main structure of this ocular segment injured
      by glaucoma.

PMID- 22618598
TI  - Very high stereoselectivity in organocatalyzed desymmetrizing aldol reactions of
      3-substituted cyclobutanones.
AB  - N-Phenylsulfonyl (S)-proline catalyzes the direct aldol reaction of 3-substituted
      cyclobutanones and aryl aldehydes in good yield and with excellent
      diastereoselectivity and enantioselectivity. This desymmetrization process
      provides highly functionalized cyclobutanones with control over three contiguous
      stereogenic centers.

PMID- 22618600
TI  - Examining talker effects in the perception of native- and foreign-accented
      speech.
AB  - Understanding the circumstances under which talker (and other types of)
      variability affects language perception represents an important area of research
      in the field of spoken word recognition. Previous work has demonstrated that
      talker effects are more likely when processing is relatively slow (McLennan &
      Luce, 2005). Given that listeners may take longer to process foreign-accented
      speech than native-accented speech (Munro & Derwing, Language and Speech, 38, 289
      306 1995), talker effects should be more likely when listeners are presented with
      words spoken in a foreign accent than when they are presented with those same
      words spoken in a native accent. The results of two experiments, conducted in two
      different countries and in two different languages, are consistent with this
      prediction.

PMID- 22618601
TI  - Commentary: chromaffin cell plasticity in stress, inflammation, development, and
      disease.

PMID- 22618602
TI  - Abstracts of the Summer Neuropeptide Conference and the European Neuropeptide
      Club (ENC) Meeting. May 22-25, 2011. Boston, Massachusetts, USA.

PMID- 22618603
TI  - Effect of enzymes on anaerobic digestion of primary sludge and septic tank
      performance.
AB  - Enzyme additives are believed to improve septic tank performance by increasing
      the hydrolysis and digestion rates and maintaining a healthy microbial
      population. Previous studies reported mixed results on the effectiveness of
      enzymes on mesophilic and thermophilic digestion, and it is not clear whether
      enzymes would be effective under septic tank conditions where there is no heating
      or mixing, quantities of enzymes added are small, and they can be washed out
      quickly. In this study, batch reactors and continuous-flow reactors designed and
      operated as septic tanks were used to evaluate whether enzymatic treatment would
      increase the hydrolysis and digestion rates in primary sludge. Total solids,
      volatile solids, total suspended solids, total and soluble chemical oxygen
      demand, concentrations of protein, carbohydrate, ammonia and volatile acids in
      sludge and effluent samples were measured to determine the differences in
      digestion rates in the presence and absence of enzymes. Overall, no significant
      improvement was observed in enzyme-treated reactors compared with the control
      reactors.

PMID- 22618604
TI  - Nuclear magnetic resonance J coupling constant polarizabilities of hydrogen
      peroxide: a basis set and correlation study.
AB  - In this article, we present the so far most extended investigation of the
      calculation of the coupling constant polarizability of a molecule. The components
      of the coupling constant polarizability are derivatives of the nuclear magnetic
      resonance (NMR) indirect nuclear spin-spin coupling constant with respect to an
      external electric field and play an important role for both chiral discrimination
      and solvation effects on NMR coupling constants. In this study, we illustrate the
      effects of one-electron basis sets and electron correlation both at the level of
      density functional theory as well as second-order polarization propagator
      approximation for the small molecule hydrogen peroxide, which allowed us to
      perform calculations with the largest available basis sets optimized for the
      calculation of NMR coupling constants. We find a systematic but rather slow
      convergence with the one-electron basis set and that augmentation functions are
      required. We observe also large and nonsystematic correlation effects with
      significant differences between the density functional and wave function theory
      methods.

PMID- 22618605
TI  - Encoding location and serial order in auditory working memory: evidence for
      separable processes.
AB  - In this study, we investigated the interactions between temporal and spatial
      information in auditory working memory. In two experiments, participants were
      presented with sequences of sounds originating from different locations in space
      and were then asked to recall either their position or their serial order. In
      Experiment 1, attention during encoding was manipulated by contrasting 'pure'
      blocks (i.e., location-only or serial-order-only trials) to 'mixed' blocks (i.e.,
      different percentages of spatial and serial-order trials). In Experiment 2,
      'pure' blocks were contrasted to blocks in which spatial and serial-order trials
      were intermixed with a third task requiring a semantic categorization of sounds.
      Results from both experiments showed that, whereas serial-order recall is
      linearly affected by the simultaneous encoding of a concurrent feature, the
      recall of position is mostly unaffected by concurrent feature encoding.
      Contrastingly, overall performance level was lower for spatial recall than serial
      recall. We concluded that serial order and location of items appear to be
      independently encoded in auditory working memory. Serial order is easier to
      recall, but strongly affected by the processing of concurrent item dimensions,
      while item location is more difficult to recall, but relatively automatic, as
      shown by its strong resistance to interfering dimensions in encoding.

PMID- 22618622
TI  - CT to the rescue in benign, symmetrical mediastinal lipomatosis.

PMID- 22618623
TI  - [Screening for colorectal cancer. Current evidence and novel developments].
AB  - CLINICAL ISSUE: Colorectal cancer is one of the leading causes of cancer-related
      morbidity and mortality. Screening has been demonstrated to reduce both the
      incidence and mortality of colorectal cancer. In addition to the large group with
      a normal risk level, two further risk groups need to be distinguished: increased
      family risk and hereditary colorectal cancer syndromes. STANDARD METHODS FOR
      SCREENING: The highest evidence for all screening tests has been demonstrated for
      guaiac-based fecal occult blood testing. Colonoscopy is a diagnostic and
      therapeutic tool and it serves as the reference standard for other tests in
      clinical studies. INNOVATIONS: Fecal immunochemical tests have a higher
      sensitivity than guaiac-based tests. Several novel techniques are under
      development and could be adopted by screening programs in the future. Next to
      colonoscopy, computed tomography (CT) colonography and colon capsule endoscopy
      have the highest sensitivity for colorectal neoplasia. Molecular tests which are
      based on the detection of genetic and epigenetic changes of DNA released by the
      tumor into feces or blood have a high potential and could potentially replace
      occult blood tests in the future. PRACTICAL RECOMMENDATIONS: Colonoscopy is the
      primary instrument for screening for colorectal neoplasia. Fecal occult blood
      testing should only be performed if colonoscopy is denied and CT colonography has
      not yet been approved for screening in Germany.

PMID- 22618624
TI  - [Rectal cancer - local staging and imaging under neoadjuvant therapy].
AB  - CLINICAL/METHODICAL ISSUE: Rectal cancer restaging after neoadjuvant therapy is
      based on two principles: an anatomic definition of the tumor allowing surgical
      planning and prognostic stage grouping. STANDARD RADIOLOGICAL METHODS: Emerging
      data suggest that reassessment using a combination of different imaging
      modalities may help to provide valuable prognostic information before definitive
      surgery. METHODICAL INNOVATIONS: Perfusion computed tomography (CT) may provide
      special information regarding tumor vascularity. PERFORMANCE: Evaluation of
      therapy response, especially of the circumferential resection margin (CRM) is
      necessary for surgical planning. ACHIEVEMENTS: For local staging high-resolution
      and diffusion-weighted magnetic resonance imaging has proven to be of high
      diagnostic accuracy. PRACTICAL RECOMMENDATIONS: The M status should be assessed
      using multidetector computed tomography (MDCT) according to response evaluation
      criteria in solid tumors (RECIST) while lymph node evaluation requires either
      magnetic resonance imaging or positron emission tomography/computed tomography
      scanning.

PMID- 22618625
TI  - [Importance of PET/CT for imaging of colorectal cancer].
AB  - CLINICAL/METHODICAL ISSUE: Fluorodeoxyglucose-positron emission
      tomography/computed tomography (FDG-PET/CT) has emerged as a very useful imaging
      modality in the management of colorectal carcinoma. Data from the literature
      regarding the role of PET/CT in the initial diagnosis, staging, radiotherapy
      planning, response monitoring and surveillance of colorectal carcinoma is
      presented. Future directions and economic aspects are discussed. STANDARD
      RADIOLOGICAL METHODS: Computed tomography (CT), magnetic resonance imaging (MRI)
      and FDG-PET for colorectal cancer and endorectal ultrasound for rectal cancer.
      METHODICAL INNOVATIONS: Combined FDG-PET/CT. PERFORMANCE: While other imaging
      modalities allow superior visualization of the extent and invasion depth of the
      primary tumor, PET/CT is most sensitive for the detection of distant metastases
      of colorectal cancer. ACHIEVEMENTS: We recommend a targeted use of PET/CT in
      cases of unclear M staging, prior to metastasectomy and in suspected cases of
      residual or recurrent colorectal carcinoma with equivocal conventional imaging.
      The role of PET/CT in radiotherapy planning and response monitoring needs to be
      determined. Currently there is no evidence to support the routine use of PET/CT
      for colorectal screening, staging or surveillance. PRACTICAL RECOMMENDATIONS: To
      optimally exploit the synergy between morphologic and functional information, FDG
      PET should generally be performed as an integrated FDG-PET/CT with a contrast
      enhanced CT component in colorectal carcinoma.

PMID- 22618626
TI  - [Importance of whole body MRI for staging of colorectal cancer].
AB  - CLINICAL/METHODICAL ISSUE: Staging and follow-up of colorectal cancer are usually
      performed with multimodal imaging strategies. These can be time-intensive and
      potentially lead to examiner-dependent bias. Alternatively, whole body magnetic
      resonance imaging (WB-MRI) provides oncologic imaging with a systemic approach.
      STANDARD RADIOLOGICAL METHODS: Ultrasound, multislice computed tomography (MSCT),
      dedicated MRI and positron emission tomography/CT (PET/CT). METHODICAL
      INNOVATIONS: High-resolution WB-MRI with focused examination of various organs,
      such as the pelvis and abdomen, lungs, brain and skeletal system, using different
      sequence and contrast techniques. PERFORMANCE: Detection of colorectal tumor
      recurrence with WB-MRI provides 83% accuracy (lymph node metastases 80%, organ
      metastases 86%). ACHIEVEMENTS: Potential cost reduction through decreased
      examination time and personnel costs. PRACTICAL RECOMMENDATIONS: Whole body MRI
      is a radiation-free alternative to standard sequential algorithms of staging and
      follow-up of colorectal cancer.

PMID- 22618627
TI  - [Radiotherapy of rectal cancer].
AB  - CLINICAL ISSUE: Despite improved screening options, most patients with rectal
      cancer are diagnosed at a locally advanced disease stage. STANDARD
      TREATMENT/PRACTICAL RECOMMENDATIONS: The treatment strategy includes preoperative
      radiochemotherapy as a cornerstone in order to improve sphincter preservation and
      local control. It is evident that radiotherapy can achieve improved local control
      even if optimal surgery (total mesorectal excision TME) is performed. TREATMENT
      INNOVATIONS, FUTURE PROSPECTS: Whether the neoadjuvant therapy should be applied
      as a long-term or short-term schedule is controversially discussed. The benefit
      of newer agents to improve systemic control is still under investigation. Modern
      radiotherapy techniques increase the effectiveness of radiochemotherapy and may
      reduce therapy-associated toxicity.

PMID- 22618628
TI  - [Tumor and pulmonary cysts - Lice, fleas or both?].
AB  - The article reports on a 60-year-old female patient with insulin-dependent
      diabetes who presented with coughing, chest pains and low-grade fever.
      Auscultation revealed a vesicular breathing noise bilaterally and the laboratory
      results showed slightly increased infection parameters. The initial diagnostic
      work-up included chest x-ray and contrast-enhanced computed tomography (CT). The
      diagnostics resulted in a pulmonary adenocarcinoma with osseous and hepatic
      metastases. Furthermore, widespread bilateral pulmonary cystic lesions were
      observed. Regarding the wide spectrum of differential diagnoses and the clinical
      pattern, the findings have to be regarded as cystic metastases and not as primary
      cystic lung disease.

PMID- 22618629
TI  - Abnormal MIBG uptake in a neuroblastoma patient with right upper lobe
      atelectasis.
AB  - A 3-month-old boy with a history of an abdominopelvic neuroblastoma presented 1
      week after tumor resection for a routine follow-up 123-I Meta-iodobenzylguanidine
      (MIBG) scan to assess for residual mass. The study demonstrated abnormal
      radiotracer uptake in the right upper lobe, which correlated on the SPECT/CT to
      an area of airspace consolidation thought to be secondary to atelectasis. To the
      best of our knowledge, there is one published case of MIBG radiotracer uptake in
      the lung correlating with pneumonia; however, there are no reported cases to date
      in the literature of focal pulmonary MIBG uptake corresponding to atelectasis.

PMID- 22618630
TI  - The effect of tumor volume on survival in patients with renal cell carcinoma.
AB  - PURPOSE: The aim of this study was to investigate the effect of tumor volume on
      prognosis and the relation of tumor volume with other prognostic factors in
      patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: The study
      included 46 retrospectively assessed patients with RCC (32 males and 14 females;
      mean age, 58.13+/-10.47 years) who underwent surgery between January 2002 and
      January 2009. Patients were staged according to clinical, radiological, and
      pathological data. The basic radiological characteristics of tumors and tumor
      volumes were defined by two observers. The clinical information and the last
      health status of all patients were recorded. The life duration of the patients
      after surgery was determined, and cumulative survival rates were calculated.
      RESULTS: The survival rates showed no difference between the male and female
      patients (P = 0.569); the five-year survival was 75.7% and 78.5%, respectively.
      The survival rates demonstrated differences between groups according to potential
      prognostic markers such as cell type, Fuhrman's grade, the diameter, invasion of
      perinephric fat, sinus, or adrenal gland, pathological stage, and presence of
      metastasis. The inter- and intra-observer reliability of radiological volume
      measurements were 93.6% and 100%, respectively (P < 0.001). Two groups of tumor
      volume (i.e., smaller and greater than 110 cm < sup > 3 < /sup > ) showed
      statistically significant difference in terms of survival (P < 0.032). In
      univariate analysis, only Fuhrman's grade and T stage were independent prognostic
      variables. CONCLUSION: Tumor volume is predictive of survival in patients with
      RCC; however, it does not appear to be an independent prognostic factor. The
      prognostic factors for overall survival are Fuhrman's grade and T stage.

PMID- 22618631
TI  - Transrectal US-guided seminal vesicle aspiration in the diagnosis of partial
      ejaculatory duct obstruction.
AB  - There has been recent interest in techniques for diagnosing ejaculatory duct    
      obstruction (EDO), especially when the partial form of the disease is suspected  
      clinically. Currently, there is no gold standard technique for diagnosing EDO. 
      Transrectal ultrasonography (TRUS), which is the technique used most widely,
      can     overdiagnose EDO. As adjunctive diagnostic techniques, duct
      chromotubation and     seminal vesiculography cannot distinguish patients with
      partial obstruction from     those without EDO. TRUS-guided seminal vesicle
      aspiration can be used in     conjunction with TRUS to confirm the diagnosis pre
      operatively, especially in     patients with seminal vesicle dilation and a
      prostatic midline/ejaculatory duct     cyst on TRUS. In patients with findings of
      chronic inflammation, such as     ejaculatory duct calcifications and seminal
      vesicle atrophy/ hypoplasia on TRUS,     proximal vasal obstruction or functional
      EDO should be excluded.

PMID- 22618632
TI  - A new classification of adenocarcinoma: what the radiologists need to know.
AB  - The International Association for the Study of Lung Cancer, American Thoracic
      Society, and European Respiratory Society recently introduced a new
      classification of lung adenocarcinoma addressing the latest advances in oncology,
      molecular biology, pathology, radiology, and surgery of lung adenocarcinoma. In
      this classification, new uniform terminology and diagnostic criteria are
      described, including the introduction of adenocarcinoma in situ as a second
      preinvasive lesion, as well as the concept of minimally-invasive adenocarcinoma
      and new subtyping of invasive adenocarcinomas stratified according to predominant
      patterns. In addition, the previously widely-used term bronchioloalveolar
      carcinoma is no longer considered valid and has been recategorized. This
      classification also provides, for the first time, guidance for small biopsies and
      cytology specimens. This new classification has profound implications for
      radiology, as much investigation will be needed to correlate these newly
      introduced concepts (such as histologic subtypes) with radiologic features.
      Understanding the newly described concept of minimally-invasive adenocarcinoma
      will be essential in determining sublobar resection for adenocarcinomas. In this
      manuscript, we briefly review the new classification of lung adenocarcinoma and
      discuss its radiologic relevance to the reporting, biopsy, and future studies of
      adenocarcinoma.

PMID- 22618633
TI  - Femtomolar detection of a cancer biomarker protein in serum with ultralow
      background current by anodic stripping voltammetry.
AB  - An electrochemical immunosensor for the detection of a cancer biomarker protein
      in serum at femtomolar concentrations with ultralow background response has been
      developed, which consists of (i) a hydrophilic polyacrylic acid brush-modified
      indium tin oxide substrate as an antifouling substrate and (ii) a graphene
      quantum dots-antibody 'bionanoconjugate' as a signal amplification label in
      voltammetric detection of targets in a glassy carbon electrode.

PMID- 22618634
TI  - Using metalloproteomics to investigate the cellular physiology of copper in
      hepatocytes.
AB  - Proteomics is a systems biology approach for examining proteins and their
      function in a given specified system. Metalloproteomics narrows the focus of
      proteomics to those proteins which bind a metal or are metalloproteins. An
      important system where metalloproteomics can be applied is the hepatocyte, the
      liver's parenchymal cell engaged in protein synthesis, nutrient deployment, and
      drug biotransformation. Hepatocellular metalloproteomics is an exciting new
      scientific discipline which has already advanced our understanding of certain
      genetic and neoplastic liver disorders. It has the potential to elucidate the
      action of numerous metals in hepatocytes and generate new diagnostic parameters,
      namely, novel biomarkers.

PMID- 22618635
TI  - Efficacy analysis of the renoprotective effects of aliskiren in hypertensive
      patients with chronic kidney disease.
AB  - We aimed to assess the effect of aliskiren treatment on blood pressure,
      albuminuria, and kidney function in patients with chronic kidney disease (CKD).
      We conducted a prospective, open-label study of 67 patients with CKD who were
      already being treated with other antihypertensives. Inclusion criteria were blood
      pressure (BP) >=130/80 mmHg, albuminuria >=30 mg/g, and estimated glomerular
      filtration rate (eGFR) >30 ml/min/1.73 m(2). Subjects were treated with 150
      mg/day aliskiren, which was increased to 300 mg/day for the 24-week study period.
      Aliskiren effectively reduced both systolic and diastolic BP, plasma renin
      activity (PRA), serum aldosterone concentration, albuminuria, urinary N-acetyl
      glucosaminidase, and urinary beta2-microglobulin levels. Although eGFR was
      significantly decreased after 4 weeks of aliskiren treatment, it recovered to a
      pretreatment level within 12 weeks of treatment initiation. There were no
      significant differences in the percent reduction of albuminuria or changes of
      eGFR levels when the subjects were divided into three groups on the basis of
      baseline eGFR (stages 1/2, 3, and 4) and the presence or absence of diabetes
      mellitus (DM group and non-DM group). Furthermore, in patients not treated with
      renin-angiotensin-aldosterone-system (RAAS) inhibitors, including angiotensin
      receptor blockers or angiotensin-converting enzyme inhibitors at baseline,
      changes in eGFR were significantly increased compared with those already treated
      with RAAS inhibitors at baseline. Aliskiren administration reduced BP, PRA, serum
      aldosterone levels, and albuminuria, while maintaining eGFR, regardless of the
      presence or absence of DM or the degree of eGFR. 

PMID- 22618636
TI  - Gut feelings and the reaction to perceived inequity: the interplay between bodily
      responses, regulation, and perception shapes the rejection of unfair offers on
      the ultimatum game.
AB  - It has been robustly demonstrated using the ultimatum game (UG) that individuals
      frequently reject unfair financial offers even if this results in a personal
      cost. One influential hypothesis for these rejections is that they reflect an
      emotional reaction to unfairness that overrides purely economic decision
      processes. In the present study, we examined whether the interplay between bodily
      responses, bodily regulation, and bodily perception ("interoception") contributes
      to emotionally driven rejection behavior on the UG. Offering support for bodily
      feedback theories, interoceptive accuracy moderated the relationship between
      changes in electrodermal activity to proposals and the behavioral rejection of
      such offers. Larger electrodermal responses to rejected relative to accepted
      offers predicted greater rejection in those with accurate interoception but were
      unrelated to rejection in those with poor interoception. Although cardiovascular
      responses during the offer period were unrelated to rejection rates, greater
      resting heart rate variability (linked to trait emotion regulation capacity)
      predicted reduced rejection rates of offers. These findings help clarify
      individual differences in reactions to perceived unfairness, support previous
      emotion regulation deficit accounts of rejection behavior, and suggest that the
      perception and regulation of bodily based emotional biasing signals ("gut
      feelings") partly shape financial decision making on the UG.

PMID- 22618638
TI  - 3-D jobs and health disparities: The health implications of Latino chicken
      catchers' working conditions.
AB  - OBJECTIVES: This study uses qualitative data to describe the tasks performed by
      chicken catchers, their organization of work, and possible health and safety
      hazards encountered. METHODS: Twenty-one Latino immigrant chicken catchers for
      North Carolina poultry-processing plants were interviewed to obtain their
      perceptions of the job and its hazards. Interviews were recorded and transcribed
      (n = 10) or detailed notes recorded (n = 11). Transcripts and notes were
      subjected to qualitative analysis. RESULTS: Chicken catching takes place in a
      highly contaminated and hazardous work environment. The fast pace of work, low
      level of control over work intensity, and piece rate compensation all result in
      high potential for work-related injury and illness, including trauma, electrical
      shock, respiratory effects, musculoskeletal injuries, and drug use. Workers
      receive little safety or job training. CONCLUSIONS: Chicken catching is
      characterized by a work environment and organization of work that promote injury
      and illness.

PMID- 22618644
TI  - Hyperuricemia in children with post-diarrheal hemolytic uremic syndrome.

PMID- 22618645
TI  - Analysis of 3-methoxypterostilbene in biological fluids by high-performance
      liquid chromatography: application to pre-clinical pharmacokinetics.
AB  - A method of analysis for 3-methoxypterostilbene [trans-3,3'5-trimethoxy
      4'hydroxystilbene] in biological fluids is necessary to study pharmacokinetics. A
      novel and simple high-performance liquid chromatographic method was developed for
      the determination of 3-methoxypterostilbene in rat serum and urine. The internal
      standard, pinosylvin, was added to 0.1 mL serum or urine (serum proteins were
      precipitated with cold acetonitrile at -20 degrees C). Separation was achieved
      with a Phenomenex(r) C(18) (2) (5 um, 250 * 4.60 mm) column with ultraviolet
      detection at 327 nm. The calibration curves in both matrices were linear ranging
      from 0.05 to 100 ug/mL, and the mean extraction efficiency was >99%. Precision of
      the assay for both matrices was <12% (RSD) and was within 13% for all points on
      the calibration curve. The limit of quantification for this method was 0.05
      ug/mL. The assay was successfully applied to a preliminary study of 3
      methoxypterostilbene pharmacokinetics in a rat.

PMID- 22618665
TI  - Estimating retinal nerve fiber layer thickness in normal schoolchildren with
      spectral-domain optical coherence tomography.
AB  - PURPOSE: To measure the peripapillary retinal nerve fiber layer (RNFL) thickness
      in normal schoolchildren with spectral domain optical coherence tomography (SD
      OCT), and to evaluate the effects of age, spherical equivalent (SE) refraction,
      OCT signal strength, and cycloplegic treatment on RNFL thickness. METHODS:
      Comprehensive ophthalmic examinations were performed at a school visit. RNFL
      thicknesses were measured with RTVue-100 OCT. Refractive errors were measured by
      cycloplegic autorefraction. RESULTS: Four hundred seventy healthy schoolchildren
      aged 7 and 12 were enrolled. The average RNFL thickness (mean +/- SD) was 109.4
      +/- 10.0 MUm. The quadrant RNFL thicknesses were 90.4 +/- 14.3 MUm (temporal),
      142.2 +/- 19.5 MUm (inferior), 71.1 +/- 11.3 MUm (nasal), and 133.9 +/- 18.1 MUm
      (superior). After controlling for age, gender, cycloplegic treatment, and signal
      strength index, multiple linear regression analysis disclosed that only SE
      refraction has a significant effect on RNFL thickness, (p < 0.001). For every
      diopter change towards hyperopia, the average RNFL thickness increased by 1.7
      MUm. SE refraction was positively correlated with RNFL thickness in most sectors
      of nontemporal quadrants, but it was negatively correlated with RNFL thickness in
      sectors of temporal quadrants. CONCLUSIONS: Our study provides reference values
      of pediatric RNFL thickness measured with SD-OCT. SE refraction is the only
      significant predictor of RNFL thickness.

PMID- 22618666
TI  - Association between HRAS rs12628 and rs112587690 polymorphisms with the risk of
      melanoma in the North American population.
AB  - HRAS belongs to the RAS genes superfamily. RAS genes are important players in
      several human tumors and the single-nucleotide polymorphism rs12628 has been
      shown to contribute to the risk of bladder, colon, gastrointestinal, oral, and
      thyroid carcinoma. We hypothesized that this SNP may affect the risk of cutaneous
      melanoma as well. HRAS gene contains a polymorphic region (rs112587690), a
      repeated hexanucleotide -GGGCCT- located in intron 1. Three alleles of this
      region, P1, P2, and P3, have been identified that contain two, three, and four
      repeats of the hexanucleotide, respectively. We investigated the clinical impact
      of these polymorphisms in a case-control study. A total of 141 melanoma patients
      and 118 healthy donors from the North America Caucasian population were screened
      for rs12628 and rs112587690 polymorphisms. Genotypes were assessed by capillary
      sequencing or fragment analysis, respectively, and rs12628 CC and rs112587690
      P1P1 genotypes significantly associated with increased melanoma risk (OR = 3.83,
      p = 0.003; OR = 11.3, p = 0.033, respectively), while rs112587690 P1P3 frequency
      resulted significantly higher in the control group (OR = 0.5, p = 0.017). These
      results suggest that rs12628 C homozygosis may be considered a potential risk
      factor for melanoma development in the North American population possibly through
      the linkage to rs112587690.

PMID- 22618667
TI  - Systemic mirnas as potential biomarkers for malignancy.
AB  - MiRNAs are a class of short, endogenous, single-stranded RNA molecules that play
      a role in the regulation of gene expression. They have been shown to modulate a
      number of cellular processes including cell differentiation, growth and apoptosis
      and as a result have been implicated in carcinogenesis. They are detectable in
      tumour tissue, and altered expression levels have been identified in various
      cancer types. Of interest, miRNAs have recently been detected and identified to
      be dysregulated in the circulation of patients with breast cancer. The fact that
      a minimally invasive test can distinguish the presence or absence of disease
      illustrates the immense potential these molecules hold as predictive markers.
      This review serves to identify those systemic miRNAs that are upregulated or
      downregulated in malignancy and how treatment impacts on their circulating
      levels. In addition, this review questions the source of these small molecules in
      the bloodstream and how they may possibly play a role in the future detection of
      cancer as either prognostic or predictive markers.

PMID- 22618668
TI  - Electrochromic enhancement of latent fingerprints by poly(3,4
      ethylenedioxythiophene).
AB  - Spatially selective electrodeposition of poly-3,4-ethylenedioxythiophene (PEDOT)
      thin films on metallic surfaces is shown to be an effective means of visualizing
      latent fingerprints. The technique exploits the fingerprint deposit as an
      insulating mask, such that electrochemical processes (here, polymer deposition)
      may only take place on deposit-free areas of the surface between the ridges of
      the fingerprint deposit; the end result is a negative image of the fingermark.
      Use of a surfactant (sodium dodecylsulphate, SDS) to solubilise the EDOT monomer
      allows the use of an aqueous electrolyte. Electrochemical (coulometric) data
      provide a total assay of deposited material, yielding spatially averaged film
      thicknesses, which are commensurate with substantive filling of the trenches
      between fingerprint deposit ridges, but not overfilling to the extent that the
      ridge detail is covered. This is confirmed by optical microscopy and AFM images,
      which show continuous polymer deposition within the trenches and good definition
      at the ridge edges. Stainless steel substrates treated in this manner and
      transferred to background electrolyte (aqueous sulphuric acid) showed enhanced
      fingerprints when the contrast between the polymer background and fingerprint
      deposit was optimised using the electrochromic properties of the PEDOT films. The
      facility of the method to reveal fingerprints of various ages and subjected to
      plausible environmental histories was demonstrated. Comparison of this
      enhancement methodology with commonly used fingerprint enhancement methods
      (dusting with powder, application of wet powder suspensions and cyanoacrylate
      fuming) showed promising performance in selected scenarios of practical interest.

PMID- 22618669
TI  - [Non-muscle invasive transitional cell carcinoma of the bladder. New developments
      in diagnostics and therapy].
AB  - Due to the high incidence and recurrence rate non-muscle invasive bladder cancer
      (NMIBC) has a relevant impact. Raman spectroscopy and optical coherence
      tomography represent innovative diagnostic tools. Urine markers still play a
      minor role in the diagnostics of NMIBC. New therapeutic options are
      thermochemotherapy and mitomycin-C electromotive drug administration (MMC-EMDA)
      as well as gemcitabine and apaziquone for intravesical administration.

PMID- 22618687
TI  - Efficient surface modification of biomaterial to prevent biofilm formation and
      the attachment of microorganisms.
AB  - Biomaterials play a fundamental role in disease management and the improvement of
      health care. In recent years, there has been a significant growth in the
      diversity, function, and number of biomaterials used worldwide. Yet, attachment
      of pathogenic microorganisms onto biomaterial surfaces remains a significant
      challenge that substantially undermines their clinical applicability, limiting
      the advancement of these systems. The emergence and escalating pervasiveness of
      antibiotic-resistant bacterial strains makes the management of biomaterial
      associated nosocomial infections increasingly difficult. The conventional post
      operative treatment of implant-caused infections using systemic antibiotics is
      often marginally effective, further accelerating the extent of antimicrobial
      resistance. Methods by which the initial stages of bacterial attachment and
      biofilm formation can be restricted or prevented are therefore sought. The
      surface modification of biomaterials has the potential to alleviate pathogenic
      biofouling, therefore preventing the need for conventional antibiotics to be
      applied.

PMID- 22618689
TI  - Spinning nanorods--active optical manipulation of semiconductor nanorods using
      polarised light.
AB  - In this letter we show how a single beam optical trap offers the means for three
      dimensional manipulation of semiconductor nanorods in solution. Furthermore
      rotation of the direction of the electric field provides control over the
      orientation of the nanorods, which is shown by polarisation analysis of two
      photon induced fluorescence. Statistics over tens of trapped agglomerates reveal
      a correlation between the measured degree of polarisation (DLP) and the size of
      the agglomerate which was determined by the escape frequency and the intensity of
      the emitted fluorescence. We estimate that we have trapped agglomerates with a
      volume of close to 10 times the volume of a single nanorod, which exhibited DLPs
      as high as 52%.

PMID- 22618688
TI  - Neo-intimal hyperplasia, diabetes and endovascular injury.
AB  - Diabetes is a significant major risk factor for peripheral arterial disease (PAD)
      and critical limb ischaemia (CLI), the latter which is also the most common cause
      of amputation in these patients. Revascularisation of the lower extremities of
      such patients is imperative for limb salvage and has become First-line therapy.
      However, the incidence of restenosis following endovascular stenting is very high
      and is largely due to neo-intimal hyperplasia (NIH), the regulation of which is
      for the greater part not understood. This article therefore reviews our
      understanding on the regulation of NIH following stent-induced vascular injury,
      and highlights the importance of future studies to investigate whether the
      profile of vascular progenitor cell differentiation, neo-intimal growth factors
      and lumen diameters predict the severity of post-stent NIH in the peripheral
      arteries. Results from future studies will (1) better our understanding of the
      regulation of NIH in general, (2) determine whether combinations of any of the
      vascular factors discussed are predictive of the extent of NIH postoperatively,
      and (3) potentially facilitate future therapeutic targets and/or change
      preventive strategies.

PMID- 22618690
TI  - Host response to xenograft ECM implantation is not different between the shoulder
      and body wall sites in the rat model.
AB  - In the context of tendon and ligament repair, mechanical loading and the presence
      of joint synovial fluid are known to profoundly influence the form and function
      of the repair tissue and potentially the host response to biomaterials.
      Previously, we demonstrated that a xenograft extra cellular matrix (ECM) scaffold
      implanted in the rat shoulder elicited a unique host response from that seen in
      the body wall. However, the host response to xenografts implanted in shoulders
      with a tendon/capsule injury was not different from xenografts implanted in
      shoulders with no injury. In the current study, we hypothesized that varying
      clinically relevant surgical and environmental factors would introduce
      significant differences in host response to xenograft implantation at the
      shoulder. Contrary to our hypothesis, we found no significant differences in host
      response between any shoulder implantation conditions or between shoulder and
      body wall implantation in the rat model. These findings suggest that there is no
      advantage to using an orthotopic shoulder model to investigate the host response
      to rotator cuff scaffold materials in the rat model, and due to the insensitivity
      of its host response to various clinically relevant surgical conditions, may
      suggest that the rat does not provide a surrogate for directly translating the
      host response to biomaterials to the human application.

PMID- 22618692
TI  - [The initial consultation with hypertension].

PMID- 22618694
TI  - [What is your diagnosis? Primary mediastinal emphysema].

PMID- 22618695
TI  - [Identification and clinical use of the Metabolic Syndrome].
AB  - The Metabolic Syndrome is characterised by the following components: atherogenic
      dyslipidemia, elevated blood pressure, elevated glucose and abdominal obesity.
      22% of 415 patients of an outpatient clinic in internal medicine fulfilled the
      criteria of a Metabolic Syndrome. The most common components were abdominal
      obesity, elevated blood pressure and elevated triglyceride. Only one in five
      treating physicians diagnosed a Metabolic Syndrome. Our data show that the
      concept of the Metabolic Syndrome has limited utility in clinical practice.

PMID- 22618691
TI  - The role of glutamine synthetase and glutamate dehydrogenase in cerebral ammonia
      homeostasis.
AB  - In the brain, glutamine synthetase (GS), which is located predominantly in
      astrocytes, is largely responsible for the removal of both blood-derived and
      metabolically generated ammonia. Thus, studies with [(13)N]ammonia have shown
      that about 25 % of blood-derived ammonia is removed in a single pass through the
      rat brain and that this ammonia is incorporated primarily into glutamine (amide)
      in astrocytes. Major pathways for cerebral ammonia generation include the
      glutaminase reaction and the glutamate dehydrogenase (GDH) reaction. The
      equilibrium position of the GDH-catalyzed reaction in vitro favors reductive
      amination of alpha-ketoglutarate at pH 7.4. Nevertheless, only a small amount of
      label derived from [(13)N]ammonia in rat brain is incorporated into glutamate and
      the alpha-amine of glutamine in vivo. Most likely the cerebral GDH reaction is
      drawn normally in the direction of glutamate oxidation (ammonia production) by
      rapid removal of ammonia as glutamine. Linkage of glutamate/alpha-ketoglutarate
      utilizing aminotransferases with the GDH reaction channels excess amino acid
      nitrogen toward ammonia for glutamine synthesis. At high ammonia levels and/or
      when GS is inhibited the GDH reaction coupled with glutamate/alpha-ketoglutarate
      linked aminotransferases may, however, promote the flow of ammonia nitrogen
      toward synthesis of amino acids. Preliminary evidence suggests an important role
      for the purine nucleotide cycle (PNC) as an additional source of ammonia in
      neurons (Net reaction: L-Aspartate + GTP + H(2)O -> Fumarate + GDP + P(i) +
      NH(3)) and in the beat cycle of ependyma cilia. The link of the PNC to
      aminotransferases and GDH/GS and its role in cerebral nitrogen metabolism under
      both normal and pathological (e.g. hyperammonemic encephalopathy) conditions
      should be a productive area for future research.

PMID- 22618696
TI  - [Cervicobrachialgia - an update under special consideration of the surgical
      management].
AB  - The classic cervicobrachialgia results acutely from cervical nerve root
      compression by disc herniation or subacutely by radicular compression after
      progressive spondylotic changes of the cervical spine. The clinical presentation
      includes local and radiating pain syndromes that can be accompanied by
      sensorimotor deficits. Besides the medical history and a targeted clinical
      examination, supplementary radiographic means should be undertaken to confirm
      diagnosis. If no urgent surgical indication exists, conservative therapy should
      be initiated. However, with varying results of conservative and surgical therapy,
      chronic impairment can occur.

PMID- 22618697
TI  - [Increased inflammatory markers].

PMID- 22618698
TI  - [An uncommon cause of iron deficiency anemia].
AB  - A 55-year-old patient was diagnosed having a malignant melanoma metastatic to the
      small bowel as cause of an iron deficiency anemia. Although up to 60% of patients
      with metastatic melanoma are found to have intestinal metastases at autopsy,
      clinically apparent gastrointestinal involvement is rare during lifetime and
      often delayed after resection of the primary tumor. Diagnostic procedures include
      radiological imaging and endoscopic modalities. Early diagnosis is desirable for
      prognostic reason both in curative and palliative settings.

PMID- 22618699
TI  - [Calcified].
AB  - A 73-year-old woman was referred due to an acute and progressive worsening of a
      previously mildly impaired kidney function of unknown origin. The kidney biopsy
      showed a phosphate nephropathy. We identified Colophos(r), a phosphate-containing
      purgative as the causing agent, which the patient had received for bowel
      cleansing for a colonoscopy one day before the detection of the acute kidney
      failure. During the following months the kidney function initially declined
      further and then improved. Most cases of phosphate nephropathy are associated
      with the ingestion of phosphate-containing purgatives. Persons at risk are women,
      elderly persons, patients with impaired kidney function, hypertension, and
      dehydration. The consequence is sometimes an irreversible tubulointerstitial
      injury that can lead to end-stage renal disease in a minority of the cases.

PMID- 22618700
TI  - [Not Available].

PMID- 22618701
TI  - [Not Available].

PMID- 22618703
TI  - [CME ORL 5. Bilateral pre-auricular swelling. Sialadenitis of all salivary glands
      in bulimia].

PMID- 22618706
TI  - [The PRISCUS list in clinical routine. Practicability and comparison to
      international PIM lists].
AB  - BACKGROUND: Certain drugs are classified as potentially inappropriate medications
      (PIM) for the elderly. In 2010, the PRISCUS list was published, specifically
      designed for its applicability in the German pharmaceutical market. The aim of
      this study was to evaluate the PRISCUS list compared to international PIM lists.
      METHODS: Based on selected PIM lists (PRISCUS, STOPP/START, Beers), the
      medications of 308 patients at a clinic of geriatric rehabilitation were screened
      for PIMs. Applying START criteria, omission of indicated drug therapies was
      detected. RESULTS: Regarding the rate of PIM detection, the PRISCUS list was less
      sensitive than the application of STOPP criteria. While hospitalized, the mean
      number of administered PIMs per patient was 1.2 based on STOPP criteria and 0.5
      based on the PRISCUS list. The lowest number of PIMs per patient was detected by
      applying the Beers list (0.4 PIMs). CONCLUSION: The Beers list should not be used
      in the German pharmaceutical market. The amendment of diagnosis-related STOPP
      criteria to the PRISCUS list would be useful to significantly advance therapeutic
      success and drug safety in the elderly.

PMID- 22618707
TI  - CCR1 blockade reduces tumor burden and osteolysis in vivo in a mouse model of
      myeloma bone disease.
AB  - The chemokine CCL3/MIP-1alpha is a risk factor in the outcome of multiple myeloma
      (MM), particularly in the development of osteolytic bone disease. This chemokine,
      highly overexpressed by MM cells, can signal mainly through 2 receptors, CCR1 and
      CCR5, only 1 of which (CCR1) is responsive to CCL3 in human and mouse osteoclast
      precursors. CCR1 activation leads to the formation of osteolytic lesions and
      facilitates tumor growth. Here we show that formation of mature osteoclasts is
      blocked by the highly potent and selective CCR1 antagonist CCX721, an analog of
      the clinical compound CCX354. We also show that doses of CCX721 selected to
      completely inhibit CCR1 produce a profound decrease in tumor burden and
      osteolytic damage in the murine 5TGM1 model of MM bone disease. Similar effects
      were observed when the antagonist was used prophylactically or therapeutically,
      with comparable efficacy to that of zoledronic acid. 5TGM1 cells were shown to
      express minimal levels of CCR1 while secreting high levels of CCL3, suggesting
      that the therapeutic effects of CCX721 result from CCR1 inhibition on non-MM
      cells, most likely osteoclasts and osteoclast precursors. These results provide a
      strong rationale for further development of CCR1 antagonists for the treatment of
      MM and associated osteolytic bone disease.

PMID- 22618708
TI  - Crystal structures of protease nexin-1 in complex with heparin and thrombin
      suggest a 2-step recognition mechanism.
AB  - Protease nexin-1 (PN1) is a specific and extremely efficient inhibitor of
      thrombin. However, unlike other thrombin inhibitors belonging to the serpin
      family, PN1 is not synthesized in the liver and does not circulate in the blood.
      Rather, PN1 is expressed by multiple cell types, including macrophages, smooth
      muscle cells, and platelets, and it is on the surface of these cells, bound to
      glycosaminoglycans, that PN1 inhibits the signaling functions of thrombin. PN1
      sets the threshold for thrombin-induced platelet activation and has been
      implicated in atherosclerosis. However, in spite of the emerging importance of
      PN1 in thrombosis and atherosclerosis, little is know about how it associates to
      cells and how it inhibits thrombin at rates that surpass the diffusion limit. To
      address these issues, we determined the crystal structures of PN1 in complex with
      heparin, and in complex with catalytically inert thrombin. The crystal structures
      suggest a unique 2-step mechanism of thrombin recognition involving rapid
      electrostatics-driven association to form an initial glycosaminoglycan-bridged
      complex, followed by a large conformational rearrangement to form the productive
      Michaelis complex.

PMID- 22618710
TI  - Citation rates for experimental psychology articles published between 1950 and
      2004: top-cited articles in behavioral cognitive psychology.
AB  - From citation rates for over 85,000 articles published between 1950 and 2004 in
      56 psychology journals, we identified a total of 500 behavioral cognitive
      psychology articles that ranked in the top 0.6% in each half-decade, in terms of
      their mean citations per year using the Web of Science. Thirty nine percent
      [corrected] of these articles were produced by 78 authors who authored three or
      more of them, and more than half were published by only five journals.The mean
      number of cites per year and the total number of citations necessary for an
      article to achieve various percentile rankings are reported for each journal. The
      mean number of citations necessary for an article published within each half
      decade to rank at any given percentile has steadily increased from 1950 to 2004.
      Of the articles that we surveyed, 11% had zero total citations, and 35% received
      fewer than four total citations. Citations for post-1994 articles ranking in the
      50th-75th and 90th-95th percentiles have generally continued to grow across each
      of their 3-year postpublication bins. For pre-1995 articles ranking in the 50th
      75th and 90th-95th percentiles, citations peaked in the 4- to 6- or 7- to 9-year
      postpublication bins and decreased linearly thereafter, until asymptoting. In
      contrast, for the top-500 articles, (a) for pre-1980 articles, citations grew and
      peaked 10-18-year postpublication bins, and after a slight decrease began to
      linearly increase again; (b) for post-1979 articles, citations have continually
      increased across years in a nearly linear fashion. We also report changes in
      topics covered by the top-cited articles over the decades.

PMID- 22618711
TI  - Moral kinematics: the role of physical factors in moral judgments.
AB  - Harmful events often have a strong physical component-for instance, car
      accidents, plane crashes, fist fights, and military interventions. Yet there has
      been very little systematic work on the degree to which physical factors
      influence our moral judgments about harm. Since physical factors are related to
      our perception of causality, they should also influence our subsequent moral
      judgments. In three experiments, we tested this prediction, focusing in
      particular on the roles of motion and contact. In Experiment 1, we used abstract
      video stimuli and found that intervening on a harmful object was judged as being
      less bad than intervening directly on the victim, and that setting an object in
      motion was judged as being worse than redirecting an already moving object.
      Experiment 2 showed that participants were sensitive not only to the presence or
      absence of motion and contact, but also to the magnitudes and frequencies
      associated with these dimensions. Experiment 3 extended the findings from
      Experiment 1 to verbally presented moral dilemmas. These results suggest that
      domain-general processes play a larger role in moral cognition than is currently
      assumed.

PMID- 22618709
TI  - Management of bleeding in acquired hemophilia A: results from the European
      Acquired Haemophilia (EACH2) Registry.
AB  - Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies to
      coagulation FVIII. Bleeding episodes at presentation are spontaneous and severe
      in most cases. Optimal hemostatic therapy is controversial, and available data
      are from observational and retrospective studies only. The EACH2 registry, a
      multicenter, pan-European, Web-based database, reports current patient
      management. The aim was to assess the control of first bleeding episodes treated
      with a bypassing agent (rFVIIa or aPCC), FVIII, or DDAVP among 501 registered
      patients. Of 482 patients with one or more bleeding episodes, 144 (30%) received
      no treatment for bleeding; 31 were treated with symptomatic therapy only. Among
      307 patients treated with a first-line hemostatic agent, 174 (56.7%) received
      rFVIIa, 63 (20.5%) aPCC, 56 (18.2%) FVIII, and 14 (4.6%) DDAVP. Bleeding was
      controlled in 269 of 338 (79.6%) patients treated with a first-line hemostatic
      agent or ancillary therapy alone. Propensity score matching was applied to allow
      unbiased comparison between treatment groups. Bleeding control was significantly
      higher in patients treated with bypassing agents versus FVIII/DDAVP (93.3% vs
      68.3%; P = .003). Bleeding control was similar between rFVIIa and aPCC (93.0%; P
      = 1). Thrombotic events were reported in 3.6% of treated patients with a similar
      incidence between rFVIIa (2.9%) and aPCC (4.8%).

PMID- 22618712
TI  - Self, others, objects: how this triadic interaction modulates our behavior.
AB  - Two experiments investigated whether the triadic interaction between objects,
      ourselves and other persons modulates motor system activation during language
      comprehension. Participants were faced with sentences formed by a descriptive
      part referring to a positive or negative emotively connoted object and an action
      part composed of an imperative verb implying a motion toward the self or toward
      other persons (e.g., "The object is attractive/ugly. Bring it toward you/Give it
      to another person/Give it to a friend"). Participants judged whether each
      sentence was sensible or not by moving the mouse toward or away from their body.
      Findings showed that the simulation of a social context influenced both (1) the
      motor system and (2) the coding of stimulus valence. Implications of the results
      for theories of embodied and social cognition are discussed.

PMID- 22618714
TI  - Plasma fluorescent oxidation products and short-term occupational particulate
      exposures.
AB  - BACKGROUND: Evidence suggests that fine particulate air pollution results in
      oxidative induced tissue damage. METHODS: A global fluorescent oxidation products
      (FLOx) assay (fluorescent intensity (FI) units per milliliter of plasma) was
      measured in blood samples collected from 236 nonsmoking, Caucasian, male trucking
      industry workers either prior to, during, or after their work shifts.
      Occupational exposures to particulate matter (PM)(2.5) were based on job-specific
      area-level sampling. Generalized linear models were used to determine
      associations between FLOx levels and PM(2.5) , adjusted for age, time since last
      meal, alcohol consumption, aspirin, and cholesterol medications. RESULTS: The
      mean (standard deviation) level of FLOx was 265.9 FI/ml (96.0). Levels of FLOx
      were higher among older individuals and lower among those who had consumed
      alcohol in the past 24 hr. However, no associations were observed between FLOx
      and PM(2.5) . CONCLUSIONS: Our results indicate no association between
      occupational PM(2.5) exposure and this marker of global oxidative stress.

PMID- 22618715
TI  - Racial and gender disparities and the role of primary tumor type on inpatient
      outcomes following craniotomy for brain metastases.
AB  - BACKGROUND: Race and gender disparities in outcomes have been documented in many
      cancers. Our study evaluated the role of race, gender, and tumor primary site in
      predicting in-hospital mortality, discharge disposition, and complications among
      patients with brain metastases. METHODS: Using Nationwide Inpatient Sample (NIS)
      data from 1998 to 2007, we evaluated in-patient outcomes of brain metastases
      patients who underwent a craniotomy in U.S. hospitals. Univariate and
      multivariate analyses were used to assess the effect of patient/tumor
      characteristics in predicting the proposed outcomes. RESULTS: NIS estimated
      78,170 patients with metastatic brain tumors underwent craniotomy between 1998
      and 2007 in the United States. Median age was 59.2 years, 52.1 % were women, and
      6.4 % were black. In-hospital mortality rate was 2.2 % with an average length of
      stay of 7.6 days. Black patients had significantly higher morbidity and
      nonroutine discharges than whites/others (p < .0001). Black women had almost
      twice the mortality (3.4 vs 1.8 %, p < .0001), a higher complication rate (24.6
      vs 18.8 %, p < .0001), longer hospital stays (10.0 vs 7.3 days, p < .0001), and
      more nonroutine discharges (45.1 vs 36.8 %, p < .0001), compared with white/other
      women. Tumor histology was a significant predictor of outcomes, with female lung
      cancer patients having the highest odds of mortality and primary gastrointestinal
      tumors having the highest number of complications. CONCLUSIONS: Evidence of race
      and gender disparities in outcomes were found in black patients, especially in
      black females who underwent surgical resection for brain metastases. These
      findings highlight an opportunity to reduce the gap of outcome disparities in
      brain metastasis patients.

PMID- 22618716
TI  - High expression of proline-rich tyrosine kinase 2 is associated with poor
      survival of hepatocellular carcinoma via regulating phosphatidylinositol 3
      kinase/AKT pathway.
AB  - BACKGROUND: The peritumoral environment has been implicated to be important in
      the process of metastasis and recurrence in hepatocellular carcinoma (HCC). Our
      aims were to assess the prognostic value of proline-rich tyrosine kinase 2 (Pyk2)
      in HCC and investigate related molecular mechanism. METHODS: Expression of Pyk2
      was tested by immunohistochemistry in tissue microarrays containing 141 paired
      HCC samples. Correlation between Pyk2 and vascular endothelial growth factor
      (VEGF) expression in clinical samples was analyzed by Spearman rank correlation.
      Matrigel invasion, anchorage-independent growth assay and immunoblotting were
      performed to study the effect of Pyk2 on the invasion and progression of HCC
      cells and phosphoinositide 3-kinase (PI3K)/AKT pathway activation. RESULTS:
      Higher Pyk2 density in both tumor and peritumor was associated with lower overall
      survival (P = 0.044; P = 0.041, respectively), serum AFP levels > 1,000 ng/ml (P
      = 0.013; P = 0.032, respectively) and postoperative distant metastasis (both P <
      0.001). However, only higher peritumoral Pyk2 density was related to lower
      disease-free survival (P = 0.014) and vascular invasion (P = 0.035). A
      significant correlation between Pyk2 and VEGF density in tumor or peritumoral
      liver tissue was observed (r = 0. 3133, P = 0.0002; r = 0.5176, P < 0.0001,
      respectively). Immunoblotting showed that Pyk2 activated PI3K-AKT pathway to
      upregulate VEGF expression in HL-7702, SMMC-7721 and HepG2 cells. CONCLUSIONS:
      High Pyk2, especially peritumoral Pyk2 was associated with poor survival, disease
      recurrence, and metastasis in HCC. PI3K-AKT pathway was involved in Pyk2-mediated
      VEGF expression during HCC progression and invasion.

PMID- 22618717
TI  - Non-vena cava venous leiomyosarcomas: a review of the literature.
AB  - BACKGROUND: Leiomyosarcoma (LMS) is a rare malignant tumor of smooth muscle
      origin that generally stems from soft tissues and uterine tissue. However, a
      small percentage of this sarcoma subset may originate from the smooth muscle of
      vessel walls, most of which are of venous origin. Although the vena cava (VC)
      serves as the most likely source for these tumors and has been well described in
      the literature, there is limited information focused on non-VC LMS derived from
      large veins. The focus of this study was to consolidate the reports and
      previously published data of all non-VC LMS of venous origin to better
      characterize and describe this disease process. METHODS: We reviewed information
      derived from 143 previously published cases. RESULTS AND CONCLUSIONS: It was
      determined that women aged 60-69 years were most commonly diagnosed with this
      particular type of tumor, with the most common tumor site being the renal vein.
      Metastasis was present in 12% of this population at the time of diagnosis, and
      32% of patients were alive 4 years later.

PMID- 22618718
TI  - The New American Joint Committee on Cancer/International Union Against Cancer
      staging system for adenocarcinoma of the stomach: increased complexity without
      clear improvement in predictive accuracy.
AB  - PURPOSE: To evaluate the changes in the 7th edition American Joint Committee on
      Cancer (AJCC) staging system for stomach cancer compared to the 6th edition; to
      compare the predictive accuracy of the two staging systems. METHODS: In a
      combined database containing 2,196 patients who underwent an R0 resection for
      gastric adenocarcinoma, differences between the two staging systems were
      evaluated and stage-specific survival estimates compared. Concordance probability
      and Brier scores were estimated for both systems to examine the predictive
      accuracy. RESULTS: Nodal status cutoff values were changed, leading to a more
      even distribution for the redefined N1, N2, and N3 group. AJCC 6th edition stage
      II reflected a highly heterogeneous population, which is now adequately
      subdivided in the AJCC 7th edition into stages IIA, IIB, and IIIA. The predictive
      accuracy of N classification improved significantly as measured by concordance.
      Despite increased complexity, the predictive accuracy of AJCC 7th stage grouping
      was significantly worse than that of the AJCC 6th edition. DISCUSSION: The
      increased complexity of the 7th edition staging system is accompanied by
      improvements in the predictive value of nodal staging as compared to the 6th
      edition, but it was no better in overall stage-specific predictive accuracy.
      Future refinements of the tumor, node, metastasis staging system should consider
      whether increased complexity is balanced by improved prognostic accuracy.

PMID- 22618719
TI  - Repeating conservative surgery after ipsilateral breast tumor reappearance:
      criteria for selecting the best candidates.
AB  - BACKGROUND: Mastectomy is still considered the treatment of first choice in
      patients with ipsilateral breast tumor recurrence (IBTR) after breast-conserving
      surgery (BCS) and whole-breast radiotherapy. METHODS: We retrospectively
      evaluated 161 patients with invasive IBTR who underwent a second BCS in order to
      describe prognosis, determine predictive factors of outcome, and select the
      subset of patients with the best local control. Median follow-up after IBTR was
      81 months. RESULTS: Median age at IBTR was 53 years. Five-year overall survival
      after IBTR was 84 % (95 % confidence interval [CI] 78-89). Five-year cumulative
      incidence of a second local event after IBTR was 29 % (95 % CI 22-37). At the
      multivariate analysis, IBTR size >2 cm and time to relapse <=48 months
      significantly increased the risk of local reappearance (hazard ratio [HR] 3.3, 95
      % CI 1.6-7.0; and HR 1.9, 95 % CI 1.1-3.5). The 5-year cumulative incidence of a
      further local reappearance of the tumor after repeating BCS was 15.2 % in the
      patients with IBTR <=2 cm and time to IBTR >48 months, 31.2 % in the patients
      with IBTR <=2 cm and time to IBTR <=48 months, and 71.2 % in patients with IBTR
      >2 cm (P < 0.001). CONCLUSIONS: The best candidates for a second BCS are those
      with small (<=2 cm) and late (>48 months) IBTR. The information about the risk of
      a further local reappearance after repeating BCS should be shared with the
      patients in the decision making process.

PMID- 22618720
TI  - Staging gastric cancer patients after complete surgical resection: which system
      should we use?

PMID- 22618721
TI  - Intraoperative molecular assessment for lymph node metastasis in head and neck
      squamous cell carcinoma using one-step nucleic acid amplification (OSNA) assay.
AB  - BACKGROUND: Conventional intraoperative pathological examination for Sentinel
      node navigation surgery (SNNS) has been controversial. We evaluated the efficacy
      of one-step nucleic acid amplification (OSNA) assay for intraoperative diagnosis
      of cervical lymph node (CLN) metastasis compared with histopathological
      examination in patients with head and neck squamous cell carcinoma (HNSCC).
      METHODS: A total of 175 CLNs dissected from 56 patients with HNSCC who underwent
      surgery at Aichi Cancer Center, Kyorin University, Gunma University or Fukushima
      Medical University, between April 2008 and December 2011 were enrolled. CLN
      samples were sectioned into four equal pieces, with two of each used for OSNA
      assay and other histopathological examinations. The diagnostic value of OSNA
      assay in HNSCC patients in predicting the results of histopathological diagnosis
      was evaluated using the area under the receiver operating characteristic (AUROC)
      curve. RESULTS: OSNA assay showed acceptable efficacy in the detection of
      pathological CLN metastasis (AUROC 0.918, 95 % confidence interval [CI] 0.852
      0.984). Regarding the CK19mRNA cutoff value, the optimum cutoff point in HNSCC
      patients was 131 copies/MUl (sensitivity: 82.4, 95 % CI 65.5-93.2; specificity:
      99.3, 95 % CI 96.1-100.0; positive likelihood ratio 116.1; negative likelihood
      ratio 0.2]. CONCLUSIONS: We demonstrated that OSNA assay is useful in
      intraoperative diagnosis for CLN metastasis in patients with HNSCC. OSNA assay
      could be applied for SNNS in HNSCC patients.

PMID- 22618722
TI  - Clinical outcomes of patients with microsatellite-unstable colorectal carcinomas
      depend on L1 methylation level.
AB  - BACKGROUND: The prognostic significance of microsatellite instability (MSI) in
      colorectal cancers (CRCs) has been addressed in many studies since the initial
      description of better survival rates in MSI-positive (MSI+) tumors than in MSI
      negative (MSI-) tumors. Recent studies have demonstrated that a higher degree of
      hypomethylation of long interspersed nuclear element-1 (L1) is related to poor
      prognosis of CRCs and that a wide variation of L1 methylation levels exist within
      MSI+ CRCs. Our aim was to identify whether L1 and Alu methylation status could
      predict clinical outcomes within MSI+ CRCs. METHODS: We analyzed 207 MSI+ CRCs
      for their methylation levels in L1 and Alu repetitive DNA elements using
      pyrosequencing and correlated them with clinicopathological information including
      survival data. RESULTS: Univariate survival analysis showed that low Alu
      methylation status (<18.60%) and low L1 methylation status (<53.00%) were
      significantly associated with shorter overall survival time (log-rank test, P =
      0.009 and P < 0.001, respectively). Multivariate analysis using nine parameters
      (Alu methylation status, L1 methylation status, patient's age, disease stage
      [tumor, node, metastasis staging system], differentiation, Crohn-like lymphoid
      reaction, KRAS/BRAF mutation status, CpG island methylator phenotype [CIMP]
      status, and peritumoral lymphocytic infiltration), which were significantly
      prognostic in MSI+ CRCs, revealed that low L1 methylation status was an
      independent prognostic factor of MSI+ CRCs (P = 0.009), whereas low Alu
      methylation status was not. CONCLUSIONS: Clinical outcomes of MSI+ CRCs depend on
      L1 methylation status, suggesting that lower L1 methylation status serves as a
      significant prognostic parameter of adverse prognosis in MSI+ CRCs.

PMID- 22618735
TI  - How does the Distress Thermometer compare to the Hospital Anxiety and Depression
      Scale for detecting possible cases of psychological morbidity among cancer
      survivors?
AB  - PURPOSE: Use of the Distress Thermometer (DT) as a screening tool is increasing
      across the cancer trajectory. This study examined the accuracy and optimal cut
      off score of the DT compared to the Hospital Anxiety and Depression Scale (HADS)
      for detecting possible cases of psychological morbidity among adults in early
      survivorship. METHODS: This study is a cross-sectional survey of 1,323 adult
      cancer survivors recruited from two state-based cancer registries in Australia.
      Participants completed the DT and the HADS at 6 months post-diagnosis. RESULTS:
      Compared to the HADS subscale threshold >=8, the DT performed well in
      discriminating between cases and non-cases of anxiety, depression and comorbid
      anxiety-depression with an area under the curve of 0.85, 0.84 and 0.87,
      respectively. A DT cut-off score of >=2 was best for clinical use (sensitivity,
      87-95 %; specificity, 60-68 %), >=4 was best for research use (sensitivity, 67-82
      %; specificity, 81-88 %) and >=3 was the best balance between sensitivity (77-88
      %) and specificity (72-79 %) for detecting cases of anxiety, depression and
      comorbid anxiety-depression. The DT demonstrated a high level of precision in
      identifying non-cases of psychological morbidity at all possible thresholds
      (negative predictive value, 77-99 %). CONCLUSIONS: The recommended DT cut-off
      score of >=4 was not supported for universal use among recent cancer survivors.
      The optimal DT threshold depends upon whether the tool is being used in the
      clinical or research setting. The DT may best serve to initially identify non
      cases as part of a two-stage screening process. The performance of the DT against
      'gold standard' clinical interview should be evaluated with cancer survivors.

PMID- 22618736
TI  - Comparison of biometrical approaches for QTL detection in multiple segregating
      families.
AB  - Detection of QTL in multiple segregating families possesses many advantages over
      the classical QTL mapping in biparental populations. It has thus become
      increasingly popular, and different biometrical approaches are available to
      analyze such data sets. We empirically compared an approach based on linkage
      mapping methodology with an association mapping approach. To this end, we used a
      large population of 788 elite maize lines derived from six biparental families
      genotyped with 857 SNP markers. In addition, we constructed genetic maps with
      reduced marker densities to assess the dependency of the performance of both
      mapping approaches on the marker density. We used cross-validation and resample
      model averaging and found that while association mapping performed better under
      high marker densities, this was reversed under low marker densities. In addition
      to main effect QTL, we also detected epistatic interactions. Our results suggest
      that both approaches will profit from a further increase in marker density and
      that a cross-validation should be applied irrespective of the biometrical
      approach.

PMID- 22618737
TI  - Macronutrient intake and risk of urothelial cell carcinoma in the European
      prospective investigation into cancer and nutrition.
AB  - Previous studies have suggested that dietary factors may be important in the
      development of bladder cancer. We examined macronutrient intake in relation to
      risk of urothelial cell carcinoma among 469,339 men and women in the European
      Prospective Investigation into Cancer and Nutrition. Associations were examined
      using Cox regression, stratified by sex, age at recruitment and centre and
      further adjusted for smoking status and duration, body mass index and total
      energy intake. After an average of 11.3 years of follow-up, 1,416 new cases of
      urothelial cell carcinoma were identified. After allowing for measurement error,
      a 3% increase in the consumption of energy intake from animal protein was
      associated with a 15% higher risk (95% confidence interval [CI]: 3-30%; p(trend) 
      = 0.01) and a 2% increase in energy from plant protein intake was associated with
      a 23% lower risk (95% CI: 36-7%, p(trend)  = 0.006). Dietary intake of fat,
      carbohydrate, fibre or calcium was not associated with risk. These findings
      suggest that animal and/or plant protein may affect the risk of urothelial cell
      carcinoma, and examination of these associations in other studies is needed.

PMID- 22618739
TI  - Dialogic reverberations: police, domestic abuse, and the discontinuance of cases.
AB  - This study investigated the social construction of domestic abuse by police
      officers, specifically in the context of arguments presented to the prosecutor
      for a decision on whether to proceed with or discontinue the case. Nineteen
      police files were examined with a particular focus on the MG3, the "Report to
      Crown Prosecutors for Charging Decision." Access to such sensitive material is
      usually denied to researchers; therefore, this study offers unusual insights into
      the treatment of victims and perpetrators of interpersonal violence by the
      police. Discourse analysis revealed three dominant speech genres: impartiality,
      credibility, and the "real" victim. These genres separately and in interaction
      served to construct domestic abuse cases in ways that did not support the
      victim's account. The "dialogic reverberations" of these findings are discussed
      and the implications of the work for research and practice are considered.

PMID- 22618738
TI  - Comparison of biochemical failure definitions for predicting local cancer
      recurrence following cryoablation of the prostate.
AB  - BACKGROUND: Various definitions of biochemical failure (BF) have been used to
      predict cancer recurrence following prostate cryoablation. However to date, none
      of these definitions have been validated for this use. We have reviewed several
      definitions of BF to determine their accuracy in predicting biopsy-proven local
      recurrence following prostate cryoablation. METHODS: The Columbia University
      Urologic Oncology Database was queried for patients who underwent prostate
      cryoablation between 1994 and 2010, and who subsequently underwent surveillance
      biopsy due to clinical suspicion of prostate cancer recurrence. Serial
      postoperative prostate-specific antigen (PSA) results were used to determine BF
      according to various definitions of BF. Biopsy results were used to determine
      local recurrence. Sensitivity, specificity, positive and negative predictive
      value, and receiver operating characteristic (ROC) curve area were calculated for
      each of the BF definitions. RESULTS: A total of 110 patients met inclusion
      criteria for the study. These patients were treated with primary full-gland (n =
      38), primary focal (n = 24), or salvage cryoablation (n = 48). On surveillance
      biopsy, 66 patients (60%) were found to have locally recurrent prostate cancer.
      The most accurate BF definition overall was PSA nadir plus 2 ng/ml (Phoenix
      definition), with sensitivity, specificity, and ROC curve area of 68%, 59%, and
      0.64, respectively. CONCLUSIONS: Overall, the Phoenix definition best predicted
      local cancer recurrence following prostate cryoablation. These preliminary data
      may be useful for researchers evaluating the short-term efficacy of cryoablation,
      and for urologists assessing their patients for potential cancer recurrence.

PMID- 22618756
TI  - Aromatic-amide-derived olefins as a springboard: isomerization-initiated
      palladium-catalyzed hydrogenation of olefins and reductive decarbonylation of
      acyl chlorides with hydrosilane.
AB  - A highly efficient catalytic protocol for the isomerization of substituted amide
      derived olefins is presented that successfully uses a hydride palladium catalyst
      system generated from [PdCl(2)(PPh(3))(2)] and HSi(OEt)(3). The Z to E
      isomerization was carried out smoothly and resulted in geometrically pure
      substituted olefins. Apart from the cis-trans isomerization of double bonds, the
      selective reduction of terminal olefins and activated alkenes was performed with
      excellent functional group tolerance in the presence of an amide-derived olefin
      ligand, and the products were obtained in high isolated yields (up to >99 %).
      Furthermore, the palladium/hydrosilane system was able to promote the reductive
      decarbonylation of benzoyl chloride when a (Z)-olefin with an aromatic amide
      moiety was used as a ligand.

PMID- 22618757
TI  - Are linear regression techniques appropriate for analysis when the dependent
      (outcome) variable is not normally distributed?

PMID- 22618758
TI  - A facile approach toward transition metal oxide hierarchical structures and their
      lithium storage properties.
AB  - A simple, non-template, non-surfactant and environmentally friendly hydrothermal
      method is presented based on the controlled release of the reactants into the
      reaction solvents to induce slow nucleation and growth of three-dimensional
      hierarchical nanostructures of transition metal oxides. This method is a general
      approach, which can be used to prepare Co(3)O(4), CuO, and Ni(OH)(2)/NiO. These
      metal oxides with hierarchical nanostructures can be used as anode materials for
      lithium-ion batteries with good Li storage performance, e.g. high specific
      capacities and stable cyclability.

PMID- 22618759
TI  - Parachordoma/myoepithelioma.

PMID- 22618760
TI  - Update on imaging of non-infectious musculoskeletal complications of HIV
      infection.
AB  - Acquired immunodeficiency syndrome (AIDS) results from infection with human
      immunodeficiency virus (HIV), producing an immunodeficient state and severe
      pathology across multiple organ systems. Musculoskeletal involvement is
      particularly prevalent in this population with both infectious and non-infectious
      complications encountered, but it is suggested that the latter will affect 72% of
      HIV-infected individuals. In this review we aim to provide an update on the
      imaging characteristics of the non-infectious manifestations. The conditions
      include HIV-related arthritis as well as various malignancies, myositis, anaemia,
      osteonecrosis, rhabdomyolysis, hypertrophic osteoarthropathy and therapy-related
      side effects. For the clinician, the diagnostic challenge lies in differentiating
      disease-related symptoms from therapy-related side effects, particularly when
      clinical and laboratory features can be non-specific. This is especially
      difficult following the widespread introduction of highly active anti-retroviral
      therapy (HAART). Imaging investigations and MRI in particular have proven vital
      for facilitating early diagnosis and enabling prompt treatment. Furthermore,
      wider availability of 18F-fluorodeoxyglucose positron emission
      tomography/computed tomography (FDG-PET/CT) has allowed whole-body assessment for
      staging and treatment response of malignancy. Understanding the pathogenesis of
      the various conditions and recognising their imaging features is essential for
      the clinical radiologist.

PMID- 22618761
TI  - Ultrasound assessment of asymmetric hypertrophy of the rectus abdominis muscle
      and prevalence of associated injury in professional tennis players.
AB  - OBJECTIVE: To assess rectus abdominis (RA) thickness and injury prevalence using
      ultrasound in a group of professional tennis players. Observations with regard to
      muscle fiber repair is described. We likewise studied the potential link between
      RA volume asymmetry and the risk of muscle strain. MATERIALS AND METHODS: The
      degree of asymmetry between the different RA slices was assessed using ultrasound
      in 61 professional tennis players. The history of RA injury in these tennis
      players was likewise studied, taking into account the following factors: dominant
      vs non-dominant arm, history of RA strains, duration thereof and number of
      recurrences. Ultrasound examination was performed with an 8- to 12-MHz linear
      multi-frequency transducer. RESULTS: Ultrasound revealed the presence of fibrous
      scar tissue in the RA muscle in 18 cases (29.5%). In all instances, the lesion
      was located in the RA on the side of the nondominant arm. In 16 of the cases, the
      lesion was infra-umbilical and L2 was affected in two cases. The mean maximum
      width of the fibrous repair tissue was 9 mm (range 5-16). The mean distance
      between the umbilicus and the scar was 5.8 cm (range 2.9-11.4). Statistical study
      of the ultrasound measurements obtained for the different slices revealed
      statistically significant differences between the different depths and according
      to arm dominance. CONCLUSIONS: In the series studied, the prevalence of RA muscle
      lesion in professional tennis players was 29.5%. Asymmetric hypertrophy of the RA
      muscle appears to constitute a risk factor for suffering an injury in this
      location.

PMID- 22618762
TI  - Effect of bone morphogenetic protein 2 on tendon-to-bone healing in a canine
      flexor tendon model.
AB  - Tendon-to-bone healing is typically poor, with a high rate of repair-site
      rupture. Bone loss after tendon-to-bone repair may contribute to poor outcomes.
      Therefore, we hypothesized that the local application of the osteogenic growth
      factor bone morphogenetic protein 2 (BMP-2) would promote bone formation, leading
      to improved repair-site mechanical properties. Intrasynovial canine flexor
      tendons were injured in Zone 1 and repaired into bone tunnels in the distal
      phalanx. BMP-2 was delivered to the repair site using either a calcium phosphate
      matrix (CPM) or a collagen sponge (COL) carrier. Each animal also received
      carrier alone in an adjacent repair to serve as an internal control. Repairs were
      evaluated at 21 days using biomechanical, radiographic, and histologic assays.
      Although an increase in osteoid formation was noted histologically, no
      significant increases in bone mineral density occurred. When excluding functional
      failures (i.e., ruptured and gapped repairs), mechanical properties were not
      different when comparing BMP-2/CPM groups with carrier controls. A significantly
      higher percentage of BMP-2 treated specimens had a maximum force <20 N compared
      to carrier controls. While tendon-to-bone healing can be enhanced by addressing
      the bone loss that typically occurs after surgical repair, the delivery of BMP-2
      using the concentrations and methods of the current study did not improve
      mechanical properties over carrier alone. The anticipated anabolic effect of BMP
      2 was insufficient in the short time frame of this study to counter the post
      repair loss of bone.

PMID- 22618763
TI  - Arsenic contamination: a potential hazard to the affected areas of West Bengal,
      India.
AB  - Arsenic contamination in groundwater is becoming more and more a worldwide
      problem. Nearing 50 million of people are at health risk from arsenic
      contamination at Ganga-Meghna-Bramhaputra basin. The experimental results of the
      five blocks under Malda district of West Bengal, India, showed that the arsenic
      concentration in groundwater (0.41-1.01 mg/l) was higher than the permissible
      limit for drinking water (0.01 mg/l) (WHO) and FAO (Food and Agriculture
      Organization) permissible limit for irrigation water (0.10 mg/l). The soil
      arsenic level (13.12 mg/kg) crossed the global average (10.0 mg/kg), but within
      the maximum acceptable limit for agricultural soil (20.0 mg/kg) recommended by
      the European Union. The total arsenic concentration on food crops varied from
      0.000 to 1.464 mg/kg of dry weight. The highest mean arsenic concentration was
      found in potato (0.456 mg/kg), followed by rice grain (0.429 mg/kg). The total
      mean arsenic content (milligrams per kg dry weight) in cereals ranged from 0.121
      to 0.429 mg/kg, in pulses and oilseeds ranged from 0.076 to 0.168 mg/kg, in tuber
      crops ranged from 0.243 to 0.456 mg/kg, in spices ranged from 0.031 to 0.175
      mg/kg, in fruits ranged from 0.021 to 0.145 mg/kg and in vegetables ranged from
      0.032 to 0.411 mg/kg, respectively. Hence, arsenic accumulation in cereals,
      pulses, oilseed, vegetables, spices, cole crop and fruits crop might not be safe
      in future without any sustainable mitigation strategies to avert the potential
      arsenic toxicity on the human health in the contaminated areas.

PMID- 22618765
TI  - Outstanding Scientific Achievement Award Lecture 2011: defeating diabesity: the
      case for personalized combinatorial therapies.

PMID- 22618766
TI  - The critical role of metabolic pathways in aging.
AB  - Aging is characterized by a deterioration in the maintenance of homeostatic
      processes over time, leading to functional decline and increased risk for disease
      and death. The aging process is characterized metabolically by insulin
      resistance, changes in body composition, and physiological declines in growth
      hormone (GH), insulin-like growth factor-1 (IGF-1), and sex steroids. Some
      interventions designed to address features of aging, such as caloric restriction
      or visceral fat depletion, have succeeded in improving insulin action and life
      span in rodents. Meanwhile, pharmacologic interventions and hormonal
      perturbations have increased the life span of several mammalian species without
      necessarily addressing features of age-related metabolic decline. These
      interventions include inhibition of the mammalian target of rapamycin and
      lifetime deficiency in GH/IGF-1 signaling. However, strategies to treat aging in
      humans, such as hormone replacement, have mostly failed to achieve their desired
      response. We will briefly discuss recent advances in our understanding of the
      complex role of metabolic pathways in the aging process and highlight important
      paradoxes that have emerged from these discoveries. Although life span has been
      the major outcome of interest in the laboratory, a special focus is made in this
      study on healthspan, as improved quality of life is the goal when translated to
      humans.

PMID- 22618767
TI  - Through the fog: recent clinical trials to preserve beta-cell function in type 1
      diabetes.

PMID- 22618769
TI  - The American Diabetes Association diabetes research perspective.

PMID- 22618768
TI  - The metabolic progression to type 1 diabetes as indicated by serial oral glucose
      tolerance testing in the Diabetes Prevention Trial-type 1.

PMID- 22618770
TI  - Emergence of a predictive clinical biomarker for diabetic neuropathy.

PMID- 22618771
TI  - How to kill two birds with one transgenic pig.

PMID- 22618772
TI  - Linking inflammation to the brain-liver axis.

PMID- 22618773
TI  - Estrogen sulfotransferase: intracrinology meets metabolic diseases.

PMID- 22618774
TI  - Mesenchymal stem cells for the treatment of diabetes.

PMID- 22618775
TI  - Maintenance of beta-cell maturity and plasticity in the adult pancreas:
      developmental biology concepts in adult physiology.

PMID- 22618779
TI  - Comment on: Gorboulev et al. Na+-D-glucose cotransporter SGLT1 Is pivotal for
      intestinal glucose absorption and glucose-dependent incretin secretion. Diabetes
      2012;61:187-196.

PMID- 22618776
TI  - Infusion of mesenchymal stem cells ameliorates hyperglycemia in type 2 diabetic
      rats: identification of a novel role in improving insulin sensitivity.
AB  - Infusion of mesenchymal stem cells (MSCs) has been shown to effectively lower
      blood glucose in diabetic individuals, but the mechanism involved could not be
      adequately explained by their potential role in promoting islet regeneration. We
      therefore hypothesized that infused MSCs might also contribute to amelioration of
      the insulin resistance of peripheral insulin target tissues. To test the
      hypothesis, we induced a diabetic rat model by high-fat diet/streptozotocin (STZ)
      administration, performed MSC infusion during the early phase (7 days) or late
      phase (21 days) after STZ injection, and then evaluated the therapeutic effects
      of MSC infusion and explored the possible mechanisms involved. MSC infusion
      ameliorated hyperglycemia in rats with type 2 diabetes (T2D). Infusion of MSCs
      during the early phase not only promoted beta-cell function but also ameliorated
      insulin resistance, whereas infusion in the late phase merely ameliorated insulin
      resistance. Infusion of MSCs resulted in an increase of GLUT4 expression and an
      elevation of phosphorylated insulin receptor substrate 1 (IRS-1) and Akt (protein
      kinase B) in insulin target tissues. This is the first report of MSC treatment
      improving insulin sensitivity in T2D. These data indicate that multiple roles and
      mechanisms are involved in the efficacy of MSCs in ameliorating hyperglycemia in
      T2D.

PMID- 22618781
TI  - Surgery for refractory mesial temporal lobe epilepsy: prognostic factors and
      early, rather than late, intervention.

PMID- 22618782
TI  - Influenza A (H1N1) induced-myopathy: an important extrapulmonary complication.

PMID- 22618783
TI  - Temporal lobe epilepsy with mesial temporal sclerosis: hippocampal neuronal loss
      as a predictor of surgical outcome.
AB  - OBJECTIVE: To analyze retrospectively a series of patients with temporal lobe
      epilepsy (TLE) and mesial temporal sclerosis (MTS), and the association of
      patterns of hippocampal sclerosis with clinical data and surgical prognosis.
      METHOD: Sixty-six patients with medically refractory TLE with unilateral MTS
      after anterior temporal lobectomy were included. Quantitative neuropathological
      evaluation was performed on NeuN-stained hippocampal sections. Patient's clinical
      data and surgical outcome were reviewed. RESULTS: Occurrence of initial
      precipitating insult (IPI), as well as better postoperative seizure control (i.e.
      Engel class 1), were associated with classical and severe patterns of hippocampal
      sclerosis (MTS type 1a and 1b, respectively). CONCLUSION: Quantitative evaluation
      of hippocampal neuronal loss patterns predicts surgical outcome in patients with
      TLE-MTS.

PMID- 22618784
TI  - Muscle biopsy features in critical ill patients with 2009 influenza A (H1N1)
      virus infection.
AB  - Higher serum creatine kinase (CK) levels in critically ill patients with a
      confirmed 2009 influenza A (H1N1) infection suggests a possible relationship
      between the H1N1 virus and muscle tissue. However, there have been no reports
      with an emphasis on muscle biopsies for patients infected with the H1N1 virus.
      The objective of this study was to investigate the histological characteristics
      of the muscle biopsies from critically ill patients with confirmed 2009 H1N1
      infections. A series of ten patients with confirmed 2009 H1N1 infection, who
      presented increased serum CK levels, was analyzed. Histological study found small
      histochemical alterations in muscles fibers (mainly in NADH, SDH, COX,
      myophosphorylase, adenylate deaminase and PAS stains), and no histological
      changes were compatible with inflammatory myopathy. Although our critically ill
      patients had elevated CK levels, they exhibited few histological/histochemical
      abnormalities in their muscle biopsy samples; however, those alterations could be
      consistent with metabolic dysfunction associated with influenza H1N1 infection.

PMID- 22618785
TI  - Combined nerve conduction index in diabetic polyneuropathy.
AB  - Diabetic polyneuropathy can be confirmed by nerve conduction studies. The data
      can be analyzed in the form of a combined index instead of individual parameters.
      METHODS: The combined index included five parameters of nerve conduction studies
      commonly used for evaluation of polyneuropathies. We evaluated sensitivity in 100
      diabetic patients with suspected polyneuropathy, and specificity in 200 non
      diabetic patients with suspected lumbosacral radiculopathy. All results were
      expressed in number of standard deviations (SD). RESULTS: The sensitivity of the
      combined index was 81 or 74%, and specificity was 97 or 98%, using respectively 
      2.0 or -2.5 SD as cutoff. The range of sensitivity of the other parameters was 57
      65% or 48-56%, and specificity range was 96-98% or 98-100%, using the same
      criteria. DISCUSSION: The combined index had higher sensitivity and equivalent
      specificity compared to isolated parameters.

PMID- 22618786
TI  - Medical conditions and body pain in patients presenting orofacial pain.
AB  - OBJECTIVE: To verify the frequency of self-reported medical conditions and pain
      areas in orofacial pain patients, comparing them with patients from the routine
      dental care. METHODS: Data were collected from archives of the Orofacial Pain
      Clinic (Group A, n=319) and of the routine dental care clinics (Group B, n=84) at
      Faculdade de Odontologia de Araraquara, Sao Paulo, in Brazil. All individuals
      answered a standardized clinical questionnaire and completed a body map
      indicating their pain areas. RESULTS: The Mann-Whitney's test demonstrated that
      Group A presented a higher mean number of medical reports than Group B (p=0.004).
      In both groups, Pearson's correlation test showed that the highest frequencies of
      medical conditions were positively correlated to highest frequencies of painful
      areas (0.478, p=0.001 and 0.246, p=0.000, respectively). CONCLUSIONS: Group A
      tended to report more medical conditions and there was a positive correlation
      between the number of medical conditions and the one of pain areas for both
      groups.

PMID- 22618787
TI  - Depression Subscale of the Hospital Anxiety and Depression Scale applied
      preoperatively in spinal surgery.
AB  - OBJECTIVE: To evaluate the accuracy of the Depression Subscale of Hospital
      Anxiety and Depression Scale (HADS-D) in spine surgery, comparing it to Beck
      Depression Inventory (BDI). METHODS: In a cross-sectional study, the HADS-D and
      the BDI were applied to patients undergoing spine surgery for lumbar (n=139) or
      cervical spondylosis (n=17). Spearman correlation tests for HADS-D and BDI were
      applied. The internal consistency of HADS-D was estimated by Cronbach's alpha
      coefficient. RESULTS: According to the BDI, the prevalence of depression was of
      28.8% (n=45). The Spearman r coefficient between HADS-D and BDI was 0.714
      (p<0.001). Cronbach's alpha for HADS-D was 0.795. The area of the ROC curve was
      0.845. Using a cutoff for HADS-D >10, there was a sensitivity of 71.1%,
      specificity of 95.4%, and positive likelihood-ratio of 15.78. CONCLUSIONS: HADS-D
      showed a strong correlation with BDI and good reliability. HADS-D is a good
      alternative for screening depression and assessing its severity.

PMID- 22618788
TI  - Cerebral hemodynamics: concepts of clinical importance.
AB  - Cerebral hemodynamics and metabolism are frequently impaired in a wide range of
      neurological diseases, including traumatic brain injury and stroke, with several
      pathophysiological mechanisms of injury. The resultant uncoupling of cerebral
      blood flow and metabolism can trigger secondary brain lesions, particularly in
      early phases, consequently worsening the patient's outcome. Cerebral blood flow
      regulation is influenced by blood gas content, blood viscosity, body temperature,
      cardiac output, altitude, cerebrovascular autoregulation, and neurovascular
      coupling, mediated by chemical agents such as nitric oxide (NO), carbon monoxide
      (CO), eicosanoid products, oxygen-derived free radicals, endothelins, K+, H+, and
      adenosine. A better understanding of these factors is valuable for the management
      of neurocritical care patients. The assessment of both cerebral hemodynamics and
      metabolism in the acute phase of neurocritical care conditions may contribute to
      a more effective planning of therapeutic strategies for reducing secondary brain
      lesions. In this review, the authors have discussed concepts of cerebral
      hemodynamics, considering aspects of clinical importance.

PMID- 22618789
TI  - Pathophysiology of acute meningitis caused by Streptococcus pneumoniae and
      adjunctive therapy approaches.
AB  - Pneumococcal meningitis is a life-threatening disease characterized by an acute
      purulent infection affecting piamater, arachnoid and the subarachnoid space. The
      intense inflammatory host's response is potentially fatal and contributes to the
      neurological sequelae. Streptococcus pneumoniae colonizes the nasopharynx,
      followed by bacteremia, microbial invasion and blood-brain barrier traversal. S.
      pneumoniae is recognized by antigen-presenting cells through the binding of Toll
      like receptors inducing the activation of factor nuclear kappa B or mitogen
      activated protein kinase pathways and subsequent up-regulation of lymphocyte
      populations and expression of numerous proteins involved in inflammation and
      immune response. Many brain cells can produce cytokines, chemokines and others
      pro-inflammatory molecules in response to bacteria stimuli, as consequence,
      polymorphonuclear are attracted, activated and released in large amounts of
      superoxide anion and nitric oxide, leading to the peroxynitrite formation,
      generating oxidative stress. This cascade leads to lipid peroxidation,
      mitochondrial damage, blood-brain barrier breakdown contributing to cell injury
      during pneumococcal meningitis.

PMID- 22618790
TI  - Brazilian guidelines for the application of transcranial ultrasound as a
      diagnostic test for the confirmation of brain death.
AB  - Neurosonological studies, specifically transcranial Doppler (TCD) and
      transcranial color-coded duplex (TCCD), have high level of specificity and
      sensitivity and they are used as complementary tests for the diagnosis of brain
      death (BD). A group of experts, from the Neurosonology Department of the
      Brazilian Academy of Neurology, created a task force to determine the criteria
      for the following aspects of diagnosing BD in Brazil: the reliability of TCD
      methodology; the reliability of TCCD methodology; neurosonology training and
      skills; the diagnosis of encephalic circulatory arrest; and exam documentation
      for BD. The results of this meeting are presented in the current paper.

PMID- 22618791
TI  - Cervical spinal cord infarct associated with patent foramen ovale.

PMID- 22618792
TI  - Complex movement disorder in an elderly patient and the chimera effect.

PMID- 22618793
TI  - Bath-related headache: a Brazilian case report.

PMID- 22618794
TI  - Medulla compression caused by vertebrobasilar dolichoectasia.

PMID- 22618795
TI  - Extensive epidural fluid collections: does it influence the outcome?

PMID- 22618800
TI  - Dynamic analysis of GI absorption and hepatic distribution processes of
      telmisartan in rats using positron emission tomography.
AB  - PURPOSE: To dynamically analyze the processes of oral absorption and
      hepatobiliary distribution of telmisartan using positron emission tomography
      (PET). METHODS: (11)C-labeled telmisartan ([(11)C]TEL) was orally administered to
      rats with or without non-radiolabeled telmisartan (0.5, and 10 mg/kg). PET
      scanning of abdominal region and whole body was performed under conscious
      condition. In situ intestinal closed loop study in rats and in vitro permeation
      study in MDR1-MDCK II cell monolayers were also conducted. RESULTS: After oral
      administration of [(11)C]TEL, systemic bioavailability and hepatic distribution
      of radioactivity increased non-linearly with dose. In the intestinal lumen, both
      telmisartan and its glucuronide were detected and the ratio of telmisartan
      decreased dramatically at high dose of telmisartan. In situ closed loop study
      showed most of telmisartan-glucuronide detected in the intestinal lumen was
      derived from the bile excretion. In addition, in vitro permeation study revealed
      that telmisartan is a substrate of P-glycoprotein. CONCLUSION: PET imaging
      analysis successfully demonstrated the processes of intestinal absorption and
      hepatic distribution of telmisartan. PET study combined with appropriate in situ
      and in vitro experiments is highly expected to be a potent tool for better
      understanding of GI absorption and subsequent tissue distribution of various
      drugs and drug candidates.

PMID- 22618801
TI  - Pharmacokinetic and pharmacodynamic modeling of opioid-induced gastrointestinal
      side effects in patients receiving tapentadol IR and oxycodone IR.
AB  - PURPOSE: To understand the relationship between the risk of opioid-related
      gastrointestinal adverse effects (AEs) and exposure to tapentadol and oxycodone
      as well as its active metabolite, oxymorphone, using
      pharmacokinetic/pharmacodynamic models. METHODS: The analysis was based on a
      study in patients with moderate-to-severe pain following bunionectomy. Population
      PK modeling was conducted to estimate population PK parameters for tapentadol,
      oxycodone, and oxymorphone. Time to AEs was analyzed using Cox proportional
      hazards models. RESULTS: Risk of nausea, vomiting, and constipation significantly
      increased with exposure to tapentadol or oxycodone/oxymorphone. However, elevated
      risk per drug exposure of AEs for tapentadol was ~3-4 times lower than that of
      oxycodone, while elevated AE risk per drug exposure of oxycodone was ~60 times
      lower than that for oxymorphone, consistent with reported in vitro receptor
      binding affinities for these compounds. Simulations show that AE incidence
      following administration of tapentadol IR is lower than that following oxycodone
      IR intake within the investigated range of analgesic noninferiority dose ratios.
      CONCLUSIONS: This PK/PD analysis supports the clinical findings of reduced
      nausea, vomiting and constipation reported by patients treated with tapentadol,
      compared to patients treated with oxycodone.

PMID- 22618802
TI  - Fabrication, characterization and in vitro evaluation of aligned PLGA-PCL
      nanofibers for neural regeneration.
AB  - Electrospun nanofibrous scaffolds have received a great deal of attention in
      tissue engineering in recent years. Bridging larger nerve gaps between proximal
      and distal ends requires exogenous tubular constructs with uniaxially aligned
      topographical cues to promote the axonal re-growth due to the lack of fibrin
      cable formation. In this study, we have designed and developed a collector to
      obtain aligned nanofibers of PLGA-PCL. The average diameter of the fibers
      obtained is 230 +/- 63 nm and the alignment of fibers is quantified by
      calculating relative angle of each fiber. The tensile strength, porosity, contact
      angle, and biodegradation of the uniaxial PLGA-PCL nanofibers are measured and
      compared with the corresponding random fibers. Pore size, Young's modulus, and
      degradation of the aligned scaffold are significantly lesser than random fibers
      (p < 0.05). The in vitro cell adhesion and proliferation of Schwann cells on the
      aligned nanofibers are evaluated and compared with random nanofibers. Our results
      demonstrate that the alignment of nanofibers has a significant influence on the
      adhesion and proliferation of Schwann cells. Thus, the axially aligned nanofibers
      may mimic the fibrin cable architecture; thereby it may represent an ideal
      scaffold for extending the growth of axonal processes.

PMID- 22618803
TI  - Toward mechanical systems biology in bone.
AB  - Cyclic mechanical loading is perhaps the most important physiological factor
      regulating bone mass and shape in a way which balances optimal strength with
      minimal weight. This bone adaptation process spans multiple length and time
      scales. Forces resulting from physiological exercise at the organ scale are
      sensed at the cellular scale by osteocytes, which reside inside the bone matrix.
      Via biochemical pathways, osteocytes orchestrate the local remodeling action of
      osteoblasts (bone formation) and osteoclasts (bone resorption). Together these
      local adaptive remodeling activities sum up to strengthen bone globally at the
      organ scale. To resolve the underlying mechanisms it is required to identify and
      quantify both cause and effect across the different scales. Progress has been
      made at the different scales experimentally. Computational models of bone
      adaptation have been developed to piece together various experimental
      observations at the different scales into coherent and plausible mechanisms.
      However additional quantitative experimental validation is still required to
      build upon the insights which have already been achieved. In this review we
      discuss emerging as well as state of the art experimental and computational
      techniques and how they might be used in a mechanical systems biology approach to
      further our understanding of the mechanisms governing load induced bone
      adaptation, i.e., ways are outlined in which experimental and computational
      approaches could be coupled, in a quantitative manner to create more reliable
      multiscale models of bone.

PMID- 22618804
TI  - A Bayesian method for estimating prevalence in the presence of a hidden sub
      population.
AB  - When estimating the prevalence of a binary trait in a population, the presence of
      a hidden sub-population that cannot be sampled will lead to nonidentifiability
      and potentially biased estimation. We propose a Bayesian model of trait
      prevalence for a weighted sample from the non-hidden portion of the population,
      by modeling the relationship between prevalence and sampling probability. We
      studied the behavior of the posterior distribution on population prevalence, with
      the large-sample limits of posterior distributions obtained in simple analytical
      forms that give intuitively expected properties. We performed MCMC simulations on
      finite samples to evaluate the effectiveness of statistical learning. We applied
      the model and the results to two illustrative datasets arising from weighted
      sampling. Our work confirms that sensible results can be obtained using Bayesian
      analysis, despite the nonidentifiability in this situation.

PMID- 22618805
TI  - Genetic polymorphisms of SCN10A are associated with functional dyspepsia in
      Japanese subjects.
AB  - BACKGROUND: Visceral sensory impulses are transmitted via C-fibers from the
      gastrointestinal tract to the central nervous system. The tetrodotoxinresistant
      (TTX-r) sodium channel, Na(V) 1.8/SNS (sensory-neuron specific), encoded by
      SCN10A, has been identified on C-fibers. We attempted to clarify the association
      between functional dyspepsia (FD) and SCN10A non-synonymous polymorphisms (2884
      A>G, 3218 C>T and 3275 T>C). METHODS: The study was performed in 642 subjects
      (345 with no symptoms and 297 with FD). We employed a multiplex polymerase chain
      reaction single-strand confirmation polymorphism (PCR-SSCP) method to detect the
      gene polymorphisms. RESULTS: The 3218 CC homozygotes had a reduced risk for the
      development of FD [odds ratio (OR) 0.589; 95 % confidence interval (CI) 0.402
      0.864; p = 0.0067]. In addition, both 2884 A>G and 3275 T>C, which were in
      linkage disequilibrium, were also associated with the development of FD (p =
      0.039 and 0.028, respectively). Each 2884 G carrier, 3218 CC homozygote, and 3275
      C carrier had a reduced risk for the development of both epigastric pain syndrome
      (EPS) and postprandial distress syndrome (PDS). The subjects with the 2884 G
      allele, 3275 C allele, and no 3218 T allele had a reduced risk for FD (OR 0.618;
      95 % CI 0.448-0.853; p = 0.0034). This haplotype was associated with a reduced
      risk for both EPS and PDS (p = 0.0011 and 0.0056, respectively). In addition,
      there was a significant association between FD and this haplotype in Helicobacter
      pylori-negative subjects (OR 0.463; 95 % CI 0279-0.9768; p = 0.0029). CONCLUSION:
      We conclude that genetic polymorphisms of SCN10A are closely associated with FD
      (both EPS and PDS), especially in H. pylori-negative subjects, in Japanese.

PMID- 22618806
TI  - Eosinophilic esophagitis in children and adolescents: epidemiology, clinical
      presentation and seasonal variation.
AB  - BACKGROUND: Eosinophilic esophagitis (EoE) is defined by infiltration of
      eosinophils in the esophageal mucosa (>20 eosinophils/hpf). The epidemiology and
      seasonal variation have not been well studied in children and adolescents.
      METHODS: Review of all esophageal biopsies performed from January 2001 to
      December 2006 on patients younger than 21 year of age, focusing on demographics,
      onset and duration of presenting symptoms, history of allergies and endoscopic
      findings. RESULTS: A total of 753 upper endoscopies were performed, 44 of which
      showed histologic evidence of EoE (5.8 %). Fifty percent of all EoE endoscopies
      were grossly normal. Onset of symptoms was 23 % in the spring, 29 % in the
      summer, 23 % in the fall and 25 % in the winter. More cases (36 %) were diagnosed
      in the fall. Time between onset of symptoms and diagnosis was 115 +/- 145 days
      (mean +/- SD). The most common presenting symptoms were vomiting (61 %),
      dysphagia (39 %), abdominal pain (34 %), feeding disorders (14 %), heartburn (14
      %), food impaction (7 %), vague chest pain (5 %) and diarrhea (5 %). Children
      presenting with vomiting and feeding disorders were younger (p < 0.02), whereas
      children presenting with heartburn and dysphagia were older (p < 0.02).
      CONCLUSIONS: The incidence of EoE did not increase between 2001 and 2006. Onset
      of symptoms did not vary by season, indicating that allergens triggering EoE are
      present all year around. Vomiting and feeding disorders are seen in young
      children, while dysphagia and heartburn are seen in older children. As endoscopic
      findings were normal in 50 % of cases, an esophageal biopsy should be performed
      in all patients with suspected EoE.

PMID- 22618807
TI  - Multisociety Sedation Curriculum for Gastrointestinal Endoscopy.

PMID- 22618809
TI  - In search of a treatment for HIV--current therapies and the role of non
      nucleoside reverse transcriptase inhibitors (NNRTIs).
AB  - The human immunodeficiency virus (HIV) causes AIDS (acquired immune deficiency
      syndrome), a disease in which the immune system progressively deteriorates,
      making sufferers vulnerable to all manner of opportunistic infections. Currently,
      world-wide there are estimated to be 34 million people living with HIV, with the
      vast majority of these living in sub-Saharan Africa. Therefore, an important
      research focus is development of new drugs that can be used in the treatment of
      HIV/AIDS. This review gives an overview of the disease and addresses the drugs
      currently used for treatment, with specific emphasis on new developments within
      the class of allosteric non-nucleoside reverse transcriptase inhibitors (NNRTIs).

PMID- 22618808
TI  - NOS2 enhances KRAS-induced lung carcinogenesis, inflammation and microRNA-21
      expression.
AB  - Mutant KRAS in lung cancers induces molecular pathways that regulate cellular
      proliferation, survival and inflammation, which enhance tumorigenesis. Inducible
      nitric oxide synthase (NOS2) upregulation and sustained nitric oxide generation
      are induced during the inflammatory response and correlate positively with lung
      tumorigenesis. To explore the mechanistic contribution of NOS2 to KRAS-induced
      lung tumorigenesis and inflammation, we used a genetic strategy of crossing NOS2
      knockout (NOS2KO) C57BL6 inbred mice with a KRAS(G12D)-driven mouse lung cancer
      model. KRAS(G12D);NOS2KO mice exhibited delayed lung tumorigenesis and a longer
      overall survival time compared to that of KRAS(G12D);NOS2WT (wild-type) controls.
      Correspondingly, tumors in KRAS(G12D);NOS2KO mice had reduced tumor cell
      proliferation in adenomas and carcinomas. NOS2 deficiency also led to markedly
      suppressed inflammatory response by attenuation of macrophage recruitment into
      alveoli and within tumor foci. In contrast, FOXP3+ regulatory T cells were
      increased in tumors from KRAS(G12D) ;NOS2KO mice. We further analyzed the
      expression of microRNA-21 (miR-21), an oncogenic noncoding RNA involved in
      oncogenic Ras signaling, by quantitative reverse-transcription polymerase chain
      reaction and in situ hybridization. Lung carcinomas dissected from
      KRAS(G12D);NOS2KO mice showed a significantly reduced miR-21 expression along
      with decreased tumor cell proliferation, suggesting that NOS2 deficiency could
      attenuate RAS signaling pathways that transactivate miR-21 expression. Therefore,
      deletion of NOS2 decreases lung tumor growth as well as inflammatory responses
      initiated by oncogenic KRAS, suggesting that both KRAS and NOS2 cooperate in
      driving lung tumorigenesis and inflammation. Inhibition of NOS2 may have a
      therapeutic value in lung cancers with oncogenic KRAS mutations.

PMID- 22618810
TI  - The patient's interpretation of myocardial infarction symptoms and its role in
      the decision process to seek treatment: the MONICA/KORA Myocardial Infarction
      Registry.
AB  - BACKGROUND: The patients' misinterpretation of symptoms of an evolving acute
      myocardial infarction (AMI) is a major cause for prolonged pre-hospital delays.
      The objective of this study was to identify factors associated with an
      attribution of the symptoms to the heart and to investigate the association
      between symptom misinterpretation and time until first medical contact (delay
      time). METHODS: The study population comprised 1,684 men and 559 women, aged 25
      74 years, hospitalized with a first-time AMI recruited from a population-based
      AMI Registry. RESULTS: A total of 50.3 % of the patients attributed their
      experienced symptoms to the heart. Logistic regression modeling revealed that
      symptoms like chest pain, pain in the left upper extremity, and fear of death
      facilitated a correct attribution to the heart, whereas symptoms like vomiting or
      pain in the right upper extremity made a correct labeling difficult. Female sex,
      low educational status, migration background, and current smoking were associated
      with a higher risk of misinterpretation of symptoms. A family history of AMI or a
      history of angina pectoris, hypertension, and hyperlipidemia were shown to
      facilitate a correct interpretation of symptoms. Variables associated with a
      misinterpretation of symptoms did not significantly differ between men and women.
      People with misinterpretation of symptoms had a 1.59-fold risk (95 % confidence
      interval 1.33-1.90) to have a delay time of at least 2 h, compared with persons
      who correctly attributed their symptoms. CONCLUSIONS: Symptom misinterpretation
      is common among patients with AMI, significantly related to symptoms,
      sociodemographic characteristics and individual risk factors, and associated with
      a prolonged delay time.

PMID- 22618811
TI  - Differentiating neural crest stem cells induce proliferation of cultured rodent
      islet beta cells.
AB  - AIMS/HYPOTHESIS: Efficient stimulation of cycling activity in cultured beta cells
      would allow the design of new strategies for cell therapy in diabetes. Neural
      crest stem cells (NCSCs) play a role in beta cell development and maturation and
      increase the beta cell number in co-transplants. The mechanism behind NCSC
      induced beta cell proliferation and the functional capacity of the new beta cells
      is not known. METHODS: We developed a new in vitro co-culture system that enables
      the dissection of the elements that control the cellular interactions that lead
      to NCSC-dependent increase in islet beta cells. RESULTS: Mouse NCSCs were
      cultured in vitro, first in medium that stimulated their proliferation, then
      under conditions that supported their differentiation. When mouse islet cells
      were cultured together with the NCSCs, more than 35% of the beta cells showed
      cycle activity. This labelling index is more than tenfold higher than control
      islets cultured without NCSCs. Beta cells that proliferated under these culture
      conditions were fully glucose responsive in terms of insulin secretion. NCSCs
      also induced beta cell proliferation in islets isolated from 1-year-old mice, but
      not in dissociated islet cells isolated from human donor pancreas tissue. To
      stimulate beta cell proliferation, NCSCs need to be in intimate contact with the
      beta cells. CONCLUSIONS/INTERPRETATION: Culture of islet cells in contact with
      NCSCs induces highly efficient beta cell proliferation. The reported culture
      system is an excellent platform for further dissection of the minimal set of
      factors needed to drive this process and explore its potential for translation to
      diabetes therapy.

PMID- 22618812
TI  - High prevalence of previously unknown heart failure and left ventricular
      dysfunction in patients with type 2 diabetes.
AB  - AIMS/HYPOTHESIS: The aim of this study was to assess the prevalence of (unknown)
      heart failure and left ventricular dysfunction in older patients with type 2
      diabetes. METHODS: In total, 605 patients aged 60 years or over with type 2
      diabetes in the south west of the Netherlands participated in this cross
      sectional study (response rate 48.7%), including 24 with a cardiologist-confirmed
      diagnosis of heart failure. Between February 2009 and March 2010, the patients
      without known heart failure underwent a standardised diagnostic work-up,
      including medical history, physical examination, ECG and echocardiography. An
      expert panel used the criteria of the European Society of Cardiology to diagnose
      heart failure. RESULTS: Of the 581 patients studied, 161 (27.7%; 95% CI 24.1%,
      31.4%) were found to have previously unknown heart failure: 28 (4.8%; 95% CI
      3.1%, 6.6%) with reduced ejection fraction, and 133 (22.9%; 95% CI 19.5%, 26.3%)
      with preserved ejection fraction. The prevalence of heart failure increased
      steeply with age. Heart failure with preserved ejection fraction was more common
      in women. Left ventricular dysfunction was diagnosed in 150 patients (25.8%; 95%
      CI 22.3%, 29.4%); 146 (25.1%; 95% CI 21.6%, 28.7%) had diastolic dysfunction.
      CONCLUSIONS/INTERPRETATION: This is the first epidemiological study that provides
      exact prevalence estimates of (previously unknown) heart failure and left
      ventricular dysfunction in a representative sample of patients with type 2
      diabetes. Previously unknown heart failure and left ventricular dysfunction are
      highly prevalent. Physicians should pay special attention to 'unmasking' these
      patients.

PMID- 22618813
TI  - Revised molecular basis of the promiscuous carboxylic acid perhydrolase activity
      in serine hydrolases.
AB  - Several serine hydrolases catalyze a promiscuous reaction: perhydrolysis of
      carboxylic acids to form peroxycarboxylic acids. The working hypothesis is that
      perhydrolases are more selective than esterases for hydrogen peroxide over water.
      In this study, we tested this hypothesis, and focused on L29P-PFE (Pseudomonas
      fluorescens esterase), which catalyzes perhydrolysis of acetic acid 43-fold
      faster than wild-type PFE. This hypothesis predicts that L29P-PFE should be
      approximately 43-fold more selective for hydrogen peroxide than wild-type PFE,
      but experiments show that L29P-PFE is less selective. The ratio of hydrolysis to
      perhydrolysis of methyl acetate at different concentrations of hydrogen peroxide
      fit a kinetic model for nucleophile selectivity. L29P-PFE (beta(0)=170  M(-1)) is
      approximately half as selective for hydrogen peroxide over water than wild-type
      PFE (beta(0)=330  M(-1)), which contradicts the working hypothesis. An
      alternative hypothesis is that carboxylic acid perhydrolases increase
      perhydrolysis by forming the acyl-enzyme intermediate faster. Consistent with
      this hypothesis, the rate of acetyl-enzyme formation, measured by (18)O-water
      exchange into acetic acid, was 25-fold faster with L29P-PFE than with wild-type
      PFE, which is similar to the 43-fold faster perhydrolysis with L29P-PFE.
      Molecular modeling of the first tetrahedral intermediate (T(d)1) suggests that a
      closer carbonyl group found in perhydrolases accepts a hydrogen bond from the
      leaving group water. This revised understanding can help design more efficient
      enzymes for perhydrolysis and shows how subtle changes can create new, unnatural
      functions in enzymes.

PMID- 22618832
TI  - Functional MRI of mild traumatic brain injury (mTBI): progress and perspectives
      from the first decade of studies.
AB  - Mild traumatic brain injury (mTBI) represents the great majority of traumatic
      brain injuries, and is a common medical problem affecting cognitive and
      vocational functioning as well as quality of life in some individuals. Functional
      MRI (fMRI) is an important research method for investigating the neuroanatomic
      substrates of cognitive disorders and their treatment. Surprisingly, however,
      relatively little research has utilized fMRI to examine alterations in brain
      functioning after mTBI. This article provides a critical overview of the
      published fMRI research on mTBI to date. These topics include examination of
      frontal lobe/executive functions such as working memory, as well as episodic
      memory and resting state/functional connectivity. mTBI has also been investigated
      in military populations where studies have focused on effects of blast injury and
      comorbid conditions such as post-traumatic stress disorder and major depressive
      disorder. Finally, we address fMRI evaluations of response to behavioral or
      pharmacological challenges and interventions targeting cognitive and behavioral
      sequelae of mTBI. The review concludes with identification and discussion of gaps
      in current knowledge and future directions for fMRI studies of mTBI. The authors
      conclude that fMRI in combination with related methods can be expected to play an
      increasing role in research related to studies of pathophysiological mechanisms
      of the sequelae of mTBI as well as in diagnosis and treatment monitoring.

PMID- 22618833
TI  - Sentinel lymph node status as most important prognostic factor in patients with
      high-risk cutaneous melanomas (tumour thickness >4.00 mm): outcome analysis from
      a single institution.
AB  - PURPOSE: Sentinel lymph node biopsy (SLNB) is considered the most powerful
      prognostic indicator of survival in patients with cutaneous melanoma of
      intermediate thickness (1-4 mm). The use of SLNB in patients with melanoma with a
      tumour thickness >4.0 mm is still controversial. The purpose of the current study
      was to determine the prognostic value of SLNB in patients with thick cutaneous
      melanomas (tumour thickness >4.0 mm) in terms of progression-free survival (PFS)
      and overall survival (OS). METHODS: A retrospective single-centre study was
      performed at the Department of Dermatology and Allergy, University of Bonn, and
      the Department of Nuclear Medicine, University of Bonn, based on data collected
      between September 2000 and January 2010. A total of 142 patients with cutaneous
      melanoma of thickness >4.00 mm were identified, and 63 of these patients
      underwent SLNB. RESULTS: Of the 63 patients in whom SLNB was performed, 25 (39.7
      %) had a positive SLN. Ulceration was more frequent in SLN-positive patients (44
      %) than in SLN-negative patients (18.4 %). The mean follow-up time for the 63
      patients was 50.7 months. Positive SLN status predicted a significantly reduced
      life expectancy in the analyses of PFS and OS. In SLN-positive patients 5-year OS
      was 76 % and in SLN-negative patients was 84.2 % (p = 0.048). Patients with a
      combination of ulcerated tumour and positive SLN had the worst prognosis.
      CONCLUSION: On the basis of our follow-up data, SLNB has to be recommended in
      patients with a tumour thickness >4.00 mm after exclusion of lymph node
      macrometastases or distant metastases. SLN status is the most significant
      prognostic factor in this group of patients.

PMID- 22618852
TI  - Tunable surface charge of ZnS:Cu nano-adsorbent induced the selective
      preconcentration of cationic dyes from wastewater.
AB  - A novel environmentally friendly nano-adsorbent is developed by doping Cu(+)
      cations into the lattice of ZnS microspheres. The adsorbent shows selective
      adsorbability for cationic dyes in low concentrations in wastewater. The adsorbed
      dye could be successfully eluted with alcohol, resulting in a 1000 fold
      enrichment of the dye solution.

PMID- 22618853
TI  - Diethylstilbestrol exposure: evaluation of the doses received in France.

PMID- 22618854
TI  - Quantification and visualization of flow in the Circle of Willis: time-resolved
      three-dimensional phase contrast MRI at 7 T compared with 3 T.
AB  - The assessment of both geometry and hemodynamics of the intracranial arteries has
      important diagnostic value in internal carotid occlusion, sickle cell disease,
      and aneurysm development. Provided that signal to noise ratio (SNR) and
      resolution are high, these factors can be measured with time-resolved three
      dimensional phase contrast MRI. However, within a given scan time duration, an
      increase in resolution causes a decrease in SNR and vice versa, hampering flow
      quantification and visualization. To study the benefits of higher SNR at 7 T,
      three-dimensional phase contrast MRI in the Circle of Willis was performed at 3 T
      and 7 T in five volunteers. Results showed that the SNR at 7 T was roughly 2.6
      times higher than at 3 T. Therefore, segmentation of small vessels such as the
      anterior and posterior communicating arteries succeeded more frequently at 7 T.
      Direction of flow and smoothness of streamlines in the anterior and posterior
      communicating arteries were more pronounced at 7 T. Mean velocity magnitude
      values in the vessels of the Circle of Willis were higher at 3 T due to noise
      compared to 7 T. Likewise, areas of the vessels were lower at 3 T. In conclusion,
      the gain in SNR at 7 T compared to 3 T allows for improved flow visualization and
      quantification in intracranial arteries.

PMID- 22618855
TI  - Automated detection of heuristics and biases among pathologists in a computer
      based system.
AB  - The purpose of this study is threefold: (1) to develop an automated, computer
      based method to detect heuristics and biases as pathologists examine virtual
      slide cases, (2) to measure the frequency and distribution of heuristics and
      errors across three levels of training, and (3) to examine relationships of
      heuristics to biases, and biases to diagnostic errors. The authors conducted the
      study using a computer-based system to view and diagnose virtual slide cases. The
      software recorded participant responses throughout the diagnostic process, and
      automatically classified participant actions based on definitions of eight common
      heuristics and/or biases. The authors measured frequency of heuristic use and
      bias across three levels of training. Biases studied were detected at varying
      frequencies, with availability and search satisficing observed most frequently.
      There were few significant differences by level of training. For
      representativeness and anchoring, the heuristic was used appropriately as often
      or more often than it was used in biased judgment. Approximately half of the
      diagnostic errors were associated with one or more biases. We conclude that
      heuristic use and biases were observed among physicians at all levels of training
      using the virtual slide system, although their frequencies varied. The system can
      be employed to detect heuristic use and to test methods for decreasing diagnostic
      errors resulting from cognitive biases. 

PMID- 22618856
TI  - The importance of seeing the patient: test-enhanced learning with standardized
      patients and written tests improves clinical application of knowledge.
AB  - Previous research has shown that repeated retrieval with written tests produces
      superior long-term retention compared to repeated study. However, the degree to
      which this increased retention transfers to clinical application has not been
      investigated. In addition, increased retention obtained through written testing
      has not been compared to other forms of testing, such as simulation testing with
      a standardized patient (SP). In our study, 41 medical students learned three
      clinical topics through three different learning activities: testing with SPs,
      testing using written tests, and studying a review sheet. Students were
      randomized in a counter-balanced fashion to engage in one learning activity per
      topic. They participated in four weekly testing/studying sessions to learn the
      material, engaging in the same activity for a given topic in each session. Six
      months after initial learning, they returned to take an SP test on each topic,
      followed by a written test on each topic 1 week later. On both forms of final
      testing, we found that learning through SP testing and written testing generally
      produced superior long-term retention compared to studying a review sheet. SP
      testing led to significantly better performance on the final SP test relative to
      written testing, but there was no significant difference between the two testing
      conditions on the final written test. Overall, our study shows that repeated
      retrieval practice with both SPs and written testing enhances long-term retention
      and transfer of knowledge to a simulated clinical application. 

PMID- 22618857
TI  - The expression of melanopsin and clock genes in Xenopus laevis melanophores and
      their modulation by melatonin.
AB  - Vertebrates have a central clock and also several peripheral clocks. Light
      responses might result from the integration of light signals by these clocks. The
      dermal melanophores of Xenopus laevis have a photoreceptor molecule denominated
      melanopsin (OPN4x). The mechanisms of the circadian clock involve positive and
      negative feedback. We hypothesize that these dermal melanophores also present
      peripheral clock characteristics. Using quantitative PCR, we analyzed the pattern
      of temporal expression of Opn4x and the clock genes Per1, Per2, Bmal1, and Clock
      in these cells, subjected to a 14-h light:10-h dark (14L:10D) regime or constant
      darkness (DD). Also, in view of the physiological role of melatonin in the dermal
      melanophores of X. laevis, we determined whether melatonin modulates the
      expression of these clock genes. These genes show a time-dependent expression
      pattern when these cells are exposed to 14L:10D, which differs from the pattern
      observed under DD. Cells kept in DD for 5 days exhibited overall increased mRNA
      expression for Opn4x and Clock, and a lower expression for Per1, Per2, and Bmal1.
      When the cells were kept in DD for 5 days and treated with melatonin for 1 h, 24
      h before extraction, the mRNA levels tended to decrease for Opn4x and Clock, did
      not change for Bmal1, and increased for Per1 and Per2 at different Zeitgeber
      times (ZT). Although these data are limited to one-day data collection, and
      therefore preliminary, we suggest that the dermal melanophores of X. laevis might
      have some characteristics of a peripheral clock, and that melatonin modulates, to
      a certain extent, melanopsin and clock gene expression.

PMID- 22618858
TI  - Retinoic acid and cAMP inhibit rat hepatocellular carcinoma cell proliferation
      and enhance cell differentiation.
AB  - Hepatocellular carcinoma (HCC) is the third highest cause of cancer death
      worldwide. In general, the disease is diagnosed at an advanced stage when
      potentially curative therapies are no longer feasible. For this reason, it is
      very important to develop new therapeutic approaches. Retinoic acid (RA) is a
      natural derivative of vitamin A that regulates important biological processes
      including cell proliferation and differentiation. In vitro studies have shown
      that RA is effective in inhibiting growth of HCC cells; however, responsiveness
      to treatment varies among different HCC cell lines. The objective of the present
      study was to determine if the combined use of RA (0.1 uM) and cAMP (1 mM), an
      important second messenger, improves the responsiveness of HCC cells to RA
      treatment. We evaluated the proliferative behavior of an HCC cell line (HTC) and
      the expression profile of genes related to cancer signaling pathway (ERK and GSK
      3beta) and liver differentiation (E-cadherin, connexin 26 (Cx26), and Cx32). RA
      and cAMP were effective in inhibiting the proliferation of HTC cells
      independently of combined use. However, when a mixture of RA and cAMP was used,
      the signals concerning the degree of cell differentiation were increased. As
      demonstrated by Western blot, the treatment increased E-cadherin, Cx26, Cx32 and
      Ser9-GSK-3beta (inactive form) expression while the expression of Cx43, Tyr216
      GSK-3beta (active form) and phosphorylated ERK decreased. Furthermore, telomerase
      activity was inhibited along treatment. Taken together, the results showed that
      the combined use of RA and cAMP is more effective in inducing differentiation of
      HTC cells.

PMID- 22618859
TI  - Development of two potential diagnostic monoclonal antibodies against human
      cytomegalovirus glycoprotein B.
AB  - Human cytomegalovirus glycoprotein B (gB) represents a target for diagnosis and
      treatment in view of the role it plays in virus entry and spread. Nevertheless,
      to our knowledge, rare detection of a gB antigen has been reported in transplant
      patients and limited information is available about diagnostic gB monoclonal
      antibodies (mAbs). Our aim was to develop gB mAbs with diagnostic potential.
      Hydrophilic gB peptides (ST: amino acids 27-40, SH: amino acids 81-94) of
      favorable immunogenicity were synthesized and used to immunize BALB/c mice. Two
      mAbs, named ZJU-FH6 and ZJU-FE6, were generated by the hybridoma technique and
      limited serial dilution and then characterized by indirect ELISA, Western
      blotting, immunoprecipitation, and immunohistochemical staining. The mAbs
      displayed high titers of specific binding affinities for the ST and SH synthetic
      peptides at an mAb dilution of 1:60,000 and 1:240,000, respectively. Western
      blotting and immunoprecipitation indicated that these mAbs recognized both
      denatured and native gB of the Towne and AD169 strains. The mAbs, when used as
      the primary antibody, showed positive staining in cells infected with both Towne
      and AD169 strains. The mAbs were then tested on patients submitted to allogeneic
      hematopoietic stem cell transplantation. The gB antigen positivity rates of the
      patients tested using ZJU-FH6 and ZJU-FE6 were 62.0 and 63.0%, respectively. The
      gB antigen showed a significant correlation with the level of pp65 antigen in
      peripheral blood leukocytes. In conclusion, two potential diagnostic gB mAbs were
      developed and were shown to be capable of recognizing gB in peripheral blood
      leukocytes in a reliable manner.

PMID- 22618860
TI  - T-cell acute lymphoblastic leukaemia after liver transplantation: post-transplant
      lymphoproliferative disorder or coincidental de novo leukaemia?
AB  - Post-transplant lymphoproliferative disorders of T-cell origin are quite
      uncommon, and the vast majority represent neoplasms of mature, post-thymic T- or
      natural killer cells. Here, we report a rare case of T-cell acute lymphoblastic
      leukaemia (T-ALL), which occurred in an 18-year-old man who had undergone three
      liver transplants, initially for biliary atresia and subsequently for graft
      failure due to chronic rejection. He had received immunosuppression with
      cyclosporine and tacrolimus, as well as short-term treatment with OKT3. The T-ALL
      occurred 16 years after the first liver transplant. This case highlights the
      challenge for classifying rare neoplasms occurring in recipients of solid organ
      transplants that are currently not recognized to lie within the spectrum of post
      transplant lymphoproliferative disorders. Given the long interval between the
      liver transplants and the development of T-ALL, a coincidental occurrence of the
      leukaemia cannot be ruled out. However, the potential roles of immunosuppressive
      therapy and other co-morbid conditions of the individual as possible risk factors
      for the pathogenesis of T-ALL are discussed.

PMID- 22618861
TI  - Microbiological and clinical characteristics of vancomycin-resistant Enterococcus
      faecium bacteraemia in Taiwan: implication of sequence type for prognosis.
AB  - OBJECTIVES: Vancomycin-resistant enterococci (VRE), particularly vancomycin
      resistant Enterococcus faecium (VREfm), have emerged among the leading pathogens
      causing hospital-acquired infections worldwide. We aimed to examine whether there
      were newly introduced clones contributing to this increase and to assess the risk
      factors for mortality in patients with VREfm bacteraemia. METHODS: Between 2003
      and 2010, all medical records of adult patients diagnosed with VREfm bacteraemia
      at a university hospital in Taiwan were reviewed. Antibiotic susceptibility,
      genotyping and multilocus sequence typing of the VREfm isolates were performed.
      RESULTS: During the study period, the prevalence of non-duplicated blood VRE
      isolates increased significantly from 3.9% in 2003 to 18.9% in 2010 (P < 0.0001).
      One-hundred-and-forty-nine patients with VREfm bacteraemia were noted and 102
      isolates of VREfm were available for microbiological characterization. All
      isolates were susceptible to daptomycin and linezolid. Sequence type (ST) 18 and
      ST414 were the two predominant emerging STs from 2009 to 2010, accounting for
      29.7% and 25.0% of all isolates, respectively. Patients who received
      immunosuppressives, had a high Charlson comorbidity index or experienced septic
      shock had a significantly higher 14 day mortality rate. Patients who had
      bacteraemia caused by ST414 isolates and received appropriate antibiotics had a
      lower 14 day mortality rate. CONCLUSIONS: The prevalence of the VRE that caused
      bacteraemia increased from 2003 to 2010. This increase might be attributed to the
      clonal spread of VREfm belonging to ST18 and ST414. The all-cause 14 day
      mortality rate was lower in patients with bacteraemia due to VREfm isolates that
      belonged to ST414.

PMID- 22618862
TI  - Bacterial stress responses as determinants of antimicrobial resistance.
AB  - Bacteria encounter a myriad of stresses in their natural environments, including,
      for pathogens, their hosts. These stresses elicit a variety of specific and
      highly regulated adaptive responses that not only protect bacteria from the
      offending stress, but also manifest changes in the cell that impact innate
      antimicrobial susceptibility. Thus exposure to nutrient starvation/limitation
      (nutrient stress), reactive oxygen and nitrogen species (oxidative/nitrosative
      stress), membrane damage (envelope stress), elevated temperature (heat stress)
      and ribosome disruption (ribosomal stress) all impact bacterial susceptibility to
      a variety of antimicrobials through their initiation of stress responses that
      positively impact recruitment of resistance determinants or promote physiological
      changes that compromise antimicrobial activity. As de facto determinants of
      antimicrobial, even multidrug, resistance, stress responses may be worthy of
      consideration as therapeutic targets.

PMID- 22618863
TI  - Backbone resonance assignments of the monomeric DUF59 domain of human Fam96a.
AB  - Proteins containing a domain of unknown function 59 (DUF59) appear to have a
      variety of physiological functions, ranging from iron-sulfur cluster assembly to
      DNA repair. DUF59 proteins have been found in bacteria, archaea and eukaryotes,
      however Fam96a and Fam96b are the only mammalian proteins predicted to contain a
      DUF59 domain. Fam96a is an 18 kDa protein comprised primarily of a DUF59 domain
      (residues 31-157) and an N-terminal signal peptide (residues 1-27).
      Interestingly, the DUF59 domain of Fam96a exists as monomeric and dimeric forms
      in solution, and X-ray crystallography studies of both forms unexpectedly
      revealed two different domain-swapped dimer structures. Here we report the
      backbone resonance assignments and secondary structure of the monomeric form of
      the 127 residue DUF59 domain of human Fam96a. This study provides the basis for
      further understanding the structural variability exhibited by Fam96a and the
      mechanism for domain swapping.

PMID- 22618864
TI  - Backbone assignment and secondary structure of Rnd1, an unusual Rho family small
      GTPase.
AB  - Rho GTPases have attracted considerable interest as signaling molecules due to
      their variety of functional roles in cells. Rnd1 is a relatively recently
      discovered Rho GTPase with no enzymatic activity against its bound GTP
      nucleotide, setting it apart from other family members. Research has revealed a
      critical role for Rnd1 not only in neurite outgrowth, dendrite development, axon
      guidance, but also in gastric cancer and in endothelial cells during
      inflammation. Structural information is crucial for understanding the mechanism
      that forms the basis for protein-protein interactions and functions, but until
      recently there were no reports of NMR studies directly on the Rnd1 protein. In
      this paper we report assignments for the majority of Rnd1 NMR resonances based on
      2D and 3D NMR spectra. Rnd1 assignment was a challenging task, however, despite
      optimization strategies that have facilitated NMR studies of the protein (Cao and
      Buck in Small GTPase 2:295-304, 2012). Besides common triple-resonance
      experiments, 3D HNCA, 3D HN(CO)CA, 3D HNCO which are usually employed for
      sequence assignment, 3D NOESY experiments and specific labeling of 13 kinds of
      amino acids were also utilized to gain as many (1)H(N), (13)C, and (15)N
      resonances assignments as possible. For 170 cross peaks observed out of 183
      possible mainchain N-H correlations in the (1)H-(15)N TROSY spectrum, backbone
      assignment was finally completed for 127 resonances. The secondary structure was
      then defined by chemical shifts and TALOS+ based on the assignments. The overall
      structure in solution compares well with that of Rnd1 in a crystal, except for
      two short segments, residues 77-83 and residues 127-131. Given that some features
      are shared among Rho GTPases, Rnd1 assignments are also compared with two other
      family members, Cdc42 and Rac1. The overall level of Rnd1 assignment is lower
      than for Cdc42 and Rac1, consistent with its lower stability and possibly
      increased internal dynamics. However, while the Rnd1 switch II region remained un
      assigned, the switch I region could be more fully assigned compared to Cdc42 and
      Rac1. The NMR assignment and structure analysis reported here provides a robust
      basis for future study of the binding between Rnd1 and other proteins, as well as
      for further studies of the molecular function of this unusual GTPase. 

PMID- 22618865
TI  - 1H, 13C and 15N resonance assignments of the pyrin domain from human PYNOD.
AB  - PYNOD is a novel protein belonging to a large family of proteins containing the
      nucleotide-binding and oligomerization domain (NOD) involved in inflammation and
      apoptosis. Human PYNOD inhibits inflammatory response mediated by caspase-1 and
      apoptosis-associated speck-like protein containing a caspase-recruitment domain
      (ASC). Here we report the (1)H, (13)C and (15)N resonance assignments and
      secondary structure identification of the pyrin domain (PYD) of human PYNOD as
      the first step towards elucidating the structural basis of the anti-inflammatory
      activity of PYNOD. 

PMID- 22618866
TI  - 1H, 13C, and 15N resonance assignments of NmtR, a Ni(II)/Co(II) metalloregulatory
      protein of Mycobacterium tuberculosis.
AB  - NmtR is a Ni(II)/Co(II)-specific repressor expressed in Mycobacterium
      tuberculosis, which regulates the transcription of a membrane transporter
      proposed to mediate cytoplasmic Ni(II)/Co(II) efflux. Here we report the backbone
      and side chain resonance assignments of the apo-NmtR and the backbone assignments
      of Ni(II)-bound form of NmtR. 

PMID- 22618867
TI  - Evaluation of an innovative Medicaid health policy initiative to expand substance
      abuse treatment in Washington State.
AB  - State health policy making is rarely based on evidence derived from empirical
      analysis. An exception is an innovative policy established in 2005 in Washington
      State (Senate Bill [SB] 5763) to provide funding (approximately $30 million) to
      expand access to substance abuse (SA) treatment for Medicaid beneficiaries. The
      authors analyzed Medicaid claims data and other administrative data over a 7-year
      period, July 2001 through June 2008, for three cohorts of welfare clients (n ~
      44,000) to assess the effect of SA treatment on health care expenditures.
      Regression analysis showed SA treatment to be associated (p < .001) with per
      member per month expenditure savings of approximately $160 to $385 depending on
      the welfare cohort. The aggregate annualized estimated saving ($16.8 million)
      equaled the cost-saving goal of SB 5763. While it may be tempting for policy
      makers to cut funding for SA treatment, this may be counterproductive and in the
      long-run increase Medicaid costs.

PMID- 22618868
TI  - Lower liver-related death in African-American women with human immunodeficiency
      virus/hepatitis C virus coinfection, compared to Caucasian and Hispanic women.
AB  - Among individuals with and without concurrent human immunodeficiency virus (HIV),
      racial/ethnic differences in the natural history of hepatitis C virus (HCV) have
      been described. African Americans have lower spontaneous HCV clearance than
      Caucasians, yet slower rates of liver fibrosis once chronically infected. It is
      not clear how these differences in the natural history of hepatitis C affect
      mortality, in either HIV-positive or -negative individuals. We conducted a cohort
      study of HIV/HCV coinfected women followed in the multicenter Women's Interagency
      HIV Study to determine the association of self-reported race/ethnicity with all
      cause and liver-related mortality. Survival analyses were performed using Cox's
      proportional hazards models. The eligible cohort (n = 794) included 140
      Caucasians, 159 Hispanics, and 495 African Americans. There were 438 deaths and
      49 liver-related deaths during a median follow-up of 8.9 years and maximum follow
      up of 16 years. African-American coinfected women had significantly lower liver
      related mortality, compared to Caucasian (hazard ratio [HR], 0.41; 95% confidence
      interval [CI]: 0.19-0.88; P = 0.022) and Hispanic coinfected women (HR, 0.38; 95%
      CI: 0.19-0.76; P = 0.006). All-cause mortality was similar between racial/ethnic
      groups (HRs for all comparisons: 0.82-1.03; log-rank test: P = 0.8). CONCLUSIONS:
      African-American coinfected women were much less likely to die from liver
      disease, as compared to Caucasians and Hispanics, independent of other causes of
      death. Future studies are needed to investigate the reasons for this marked
      racial/ethnic discrepancy in liver-related mortality.

PMID- 22618869
TI  - VarioWatch: providing large-scale and comprehensive annotations on human genomic
      variants in the next generation sequencing era.
AB  - VarioWatch (http://genepipe.ncgm.sinica.edu.tw/variowatch/) has been vastly
      improved since its former publication GenoWatch in the 2008 Web Server Issue. It
      is now at least 10 000-times faster in annotating a variant. Drastic speed
      increase, through complete re-design of its working mechanism, makes VarioWatch
      capable of annotating millions of human genomic variants generated from next
      generation sequencing in minutes, if not seconds. While using MegaQuery of
      VarioWatch to quickly annotate variants, users can apply various filters to
      retrieve a subgroup of variants according to the risk levels, interested regions,
      etc. that satisfy users' requirements. In addition to performance leap, many new
      features have also been added, such as annotation on novel variants, functional
      analyses on splice sites and in/dels, detailed variant information in tabulated
      form, plus a risk level decision tree regarding the analyzed variant. Up to 1000
      target variants can be visualized with our carefully designed Genome View, Gene
      View, Transcript View and Variation View. Two commonly used reference versions,
      NCBI build 36.3 and NCBI build 37.2, are supported. VarioWatch is unique in its
      ability to annotate comprehensively and efficiently millions of variants online,
      immediately delivering the results in real time, plus visualizes up to 1000
      annotated variants.

PMID- 22618870
TI  - Cryptic transcripts from a ubiquitous plasmid origin of replication confound
      tests for cis-regulatory function.
AB  - A vast amount of research on the regulation of gene expression has relied on
      plasmid reporter assays. In this study, we show that plasmids widely used for
      this purpose constitutively produce substantial amounts of RNA from a TATA
      containing cryptic promoter within the origin of replication. Readthrough of
      these RNAs into the intended transcriptional unit potently stimulated reporter
      activity when the inserted test sequence contained a 3' splice site (ss). We show
      that two human sequences, originally reported to be internal ribosome entry sites
      and later to instead be promoters, mimic both types of element in dicistronic
      reporter assays by causing these cryptic readthrough transcripts to splice in
      patterns that allow efficient translation of the downstream cistron. Introduction
      of test sequences containing 3' ss into monocistronic luciferase reporter vectors
      widely used in the study of transcriptional regulation also created the false
      appearance of promoter function via the same mechanism. Across a large number of
      variants of these plasmids, we found a very highly significant correlation
      between reporter activity and levels of such spliced readthrough transcripts.
      Computational estimation of the frequency of cryptic 3' ss in genomic sequences
      suggests that misattribution of cis-regulatory function may be a common
      occurrence.

PMID- 22618871
TI  - NetAligner--a network alignment server to compare complexes, pathways and whole
      interactomes.
AB  - The many ongoing genome sequencing initiatives are delivering comprehensive lists
      of the individual molecular components present in an organism, but these reveal
      little about how they work together. Follow-up initiatives are revealing
      thousands of interrelationships between gene products that need to be analyzed
      with novel bioinformatics approaches able to capture their complex emerging
      properties. Recently, we developed NetAligner, a novel network alignment tool
      that allows the identification of conserved protein complexes and pathways across
      organisms, providing valuable hints as to how those interaction networks evolved.
      NetAligner includes the prediction of likely conserved interactions, based on
      evolutionary distances, to counter the high number of missing interactions in
      current interactome networks, and a fast assessment of the statistical
      significance of individual alignment solutions, which increases its performance
      with respect to existing tools. The web server implementation of the NetAligner
      algorithm presented here features complex, pathway and interactome to interactome
      alignments for seven model organisms, namely Homo sapiens, Mus musculus,
      Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana,
      Saccharomyces cerevisiae and Escherichia coli. The user can query complexes and
      pathways of arbitrary topology against a target species interactome, or directly
      compare two complete interactomes to identify conserved complexes and
      subnetworks. Alignment solutions can be downloaded or directly visualized in the
      browser. The NetAligner web server is publicly available at
      http://netaligner.irbbarcelona.org/.

PMID- 22618872
TI  - A new method for evaluating the specificity of indirect readout in protein-DNA
      recognition.
AB  - Proteins recognize a specific DNA sequence not only through direct contact
      (direct readout) with base pairs but also through sequence-dependent conformation
      and/or flexibility of DNA (indirect readout). However, it is difficult to assess
      the contribution of indirect readout to the sequence specificity. What is needed
      is a straightforward method for quantifying its contributions to specificity.
      Using Bayesian statistics, we derived the probability of a particular sequence
      for a given DNA structure from the trajectories of molecular dynamics (MD)
      simulations of DNAs containing all possible tetramer sequences. Then, we
      quantified the specificity of indirect readout based on the information entropy
      associated with the probability. We tested this method with known structures of
      protein-DNA complexes. This method enabled us to correctly predict those regions
      where experiments suggested the involvement of indirect readout. The results also
      indicated new regions where the indirect readout mechanism makes major
      contributions to the recognition. The present method can be used to estimate the
      contribution of indirect readout without approximations to the distributions in
      the conformational ensembles of DNA, and would serve as a powerful tool to study
      the mechanism of protein-DNA recognition.

PMID- 22618873
TI  - Direct comparison of small RNA and transcription factor signaling.
AB  - Small RNAs (sRNAs) and proteins acting as transcription factors (TFs) are the
      principal components of gene networks. These two classes of signaling molecules
      have distinct mechanisms of action; sRNAs control mRNA translation, whereas TFs
      control mRNA transcription. Here, we directly compare the properties of sRNA and
      TF signaling using mathematical models and synthetic gene circuits in Escherichia
      coli. We show the abilities of sRNAs to act on existing target mRNAs (as opposed
      to TFs, which alter the production of future target mRNAs) and, without needing
      to be first translated, have surprisingly little impact on the dynamics. Instead,
      the dynamics are primarily determined by the clearance rates, steady-state
      concentrations and response curves of the sRNAs and TFs; these factors determine
      the time delay before a target gene's expression can maximally respond to changes
      in sRNA and TF transcription. The findings are broadly applicable to the analysis
      of signaling in gene networks, and we demonstrate that they can be used to
      rationally reprogram the dynamics of synthetic circuits.

PMID- 22618874
TI  - Plasma exosomes can deliver exogenous short interfering RNA to monocytes and
      lymphocytes.
AB  - Despite the promise of RNA interference (RNAi) and its potential, e.g. for use in
      cancer therapy, several technical obstacles must first be overcome. The major
      hurdle of RNAi-based therapeutics is to deliver nucleic acids across the cell's
      plasma membrane. This study demonstrates that exosome vesicles derived from
      humans can deliver short interfering RNA (siRNA) to human mononuclear blood
      cells. Exosomes are nano-sized vesicles of endocytic origin that are involved in
      cell-to-cell communication, i.e. antigen presentation, tolerance development and
      shuttle RNA (mainly mRNA and microRNA). Having tested different strategies, an
      optimized method (electroporation) was used to introduce siRNA into human
      exosomes of various origins. Plasma exosomes (exosomes from peripheral blood)
      were used as gene delivery vector (GDV) to transport exogenous siRNA to human
      blood cells. The vesicles effectively delivered the administered siRNA into
      monocytes and lymphocytes, causing selective gene silencing of mitogen-activated
      protein kinase 1. These data suggest that human exosomes can be used as a GDV to
      provide cells with heterologous nucleic acids such as therapeutic siRNAs.

PMID- 22618875
TI  - The evolutionary dynamics of functional modules and the extraordinary plasticity
      of regulons: the Escherichia coli perspective.
AB  - Using profiles of phylogenetic profiles (P-cubic) we compared the evolutionary
      dynamics of different kinds of functional associations. Ordered from most to
      least evolutionarily stable, these associations were genes in the same operons,
      genes whose products participate in the same biochemical pathway, genes coding
      for physically interacting proteins and genes in the same regulons. Regulons
      showed the most plastic functional interactions with evolutionary stabilities
      barely better than those of unrelated genes. Further regulon analyses showed that
      global regulators contain less evolutionarily stable associations than local
      regulators. Genes co-repressed by global regulators had a higher evolutionary
      conservation than genes co-activated by global regulators. However, the reverse
      was true for genes co-repressed and co-activated by local regulators. Of all the
      regulon-related associations, the relationship between regulators and their
      target genes showed the most evolutionary stability. Different negative data sets
      built to contrast against each of the analysed kinds of modules also differed in
      evolutionary conservation revealing further underlying genome organization.
      Applying P-cubic analyses to other genomes might help visualize genome
      organization, understand the evolutionary importance and plasticity of functional
      associations and compare the quality of data sets expected to reflect functional
      interactions, such as those coming from high-throughput experiments.

PMID- 22618876
TI  - Comparative genomic and proteomic analyses of PE/PPE multigene family of
      Mycobacterium tuberculosis H37Rv and H37Ra reveal novel and interesting
      differences with implications in virulence.
AB  - Tuberculosis, caused by Mycobacterium tuberculosis, remains a leading infectious
      disease taking one human life every 15 s globally. The two well-characterized
      strains H(37)Rv and H(37)Ra, derived from the same parental strain M.
      tuberculosis H(37), show dramatically different pathogenic phenotypes. PE/PPE
      gene family, comprising of 176 open reading frames and present exclusively in
      genus Mycobacterium, accounts for ~10% of the M. tuberculosis genome. Our
      comprehensive in silico analyses of PE/PPE family of H(37)Ra and virulent H(37)Rv
      strains revealed genetic differences between these strains in terms of several
      single nucleotide variations and InDels and these manifested in changes in
      physico-chemical properties, phosphorylation sites, and protein: protein
      interacting domains of the corresponding proteomes. Similar comparisons using the
      13 sigma factor genes, 36 members of the mammalian cell entry family, 13
      mycobacterial membrane protein large family members and 11 two-component signal
      transduction systems along with 5 orphaned response regulators and 2 orphaned
      sensor kinases failed to reveal very significant difference between H(37)Rv and
      H(37)Ra, reinforcing the importance of PE/PPE genes. Many of these changes
      between H(37)Rv and H(37)Ra can be correlated to differences in pathogenesis and
      virulence of the two strains.

PMID- 22618877
TI  - TaxMan: a server to trim rRNA reference databases and inspect taxonomic coverage.
AB  - Amplicon sequencing of the hypervariable regions of the small subunit ribosomal
      RNA gene is a widely accepted method for identifying the members of complex
      bacterial communities. Several rRNA gene sequence reference databases can be used
      to assign taxonomic names to the sequencing reads using BLAST, USEARCH, GAST or
      the RDP classifier. Next-generation sequencing methods produce ample reads, but
      they are short, currently ~100-450 nt (depending on the technology), as compared
      to the full rRNA gene of ~1550 nt. It is important, therefore, to select the
      right rRNA gene region for sequencing. The primers should amplify the species of
      interest and the hypervariable regions should differentiate their taxonomy. Here,
      we introduce TaxMan: a web-based tool that trims reference sequences based on
      user-selected primer pairs and returns an assessment of the primer specificity by
      taxa. It allows interactive plotting of taxa, both amplified and missed in silico
      by the primers used. Additionally, using the trimmed sequences improves the speed
      of sequence matching algorithms. The smaller database greatly improves run times
      (up to 98%) and memory usage, not only of similarity searching (BLAST), but also
      of chimera checking (UCHIME) and of clustering the reads (UCLUST). TaxMan is
      available at http://www.ibi.vu.nl/programs/taxmanwww/.

PMID- 22618878
TI  - PocketAnnotate: towards site-based function annotation.
AB  - A computational pipeline PocketAnnotate for functional annotation of proteins at
      the level of binding sites has been proposed in this study. The pipeline
      integrates three in-house algorithms for site-based function annotation:
      PocketDepth, for prediction of binding sites in protein structures; PocketMatch,
      for rapid comparison of binding sites and PocketAlign, to obtain detailed
      alignment between pair of binding sites. A novel scheme has been developed to
      rapidly generate a database of non-redundant binding sites. For a given input
      protein structure, putative ligand-binding sites are identified, matched in real
      time against the database and the query substructure aligned with the promising
      hits, to obtain a set of possible ligands that the given protein could bind to.
      The input can be either whole protein structures or merely the substructures
      corresponding to possible binding sites. Structure-based function annotation at
      the level of binding sites thus achieved could prove very useful for cases where
      no obvious functional inference can be obtained based purely on sequence or fold
      level analyses. An attempt has also been made to analyse proteins of no known
      function from Protein Data Bank. PocketAnnotate would be a valuable tool for the
      scientific community and contribute towards structure-based functional inference.
      The web server can be freely accessed at
      http://proline.biochem.iisc.ernet.in/pocketannotate/.

PMID- 22618879
TI  - A small ribozyme with dual-site kinase activity.
AB  - Phosphoryl transfer onto backbone hydroxyls is a recognized catalytic activity of
      nucleic acids. We find that kinase ribozyme K28 possesses an unusually complex
      active site that promotes (thio)phosphorylation of two residues widely separated
      in primary sequence. After allowing the ribozyme to radiolabel itself by
      phosphoryl transfer from [gamma-(32)P]GTP, DNAzyme-mediated cleavage yielded two
      radiolabeled cleavage fragments, indicating phosphorylation sites within each of
      the two cleavage fragments. These sites were mapped by alkaline digestion and
      primer extension pausing. Enzymatic digestion and mutational analysis identified
      nucleotides important for activity and established the active structure as being
      a constrained pseudoknot with unusual connectivity that may juxtapose the two
      reactive sites. Nuclease sensitivities for nucleotides near the pseudoknot core
      were altered in the presence of GTPgammaS, indicating donor-induced folding. The
      5' target site was more strongly favored in full-length ribozyme K28 (128 nt)
      than in truncated RNAs (58 nt). Electrophoretic mobilities of self
      thiophosphorylated products on organomercurial gels are distinct from the 5' mono
      thiophosphorylated product produced by reaction with polynucleotide kinase,
      potentially indicating simultaneous labeling of both sites within individual RNA
      strands. Our evidence supports a single, compact structure with local dynamics,
      rather than global rearrangement, as being responsible for dual-site
      phosphorylation.

PMID- 22618880
TI  - MAGIA2: from miRNA and genes expression data integrative analysis to microRNA
      transcription factor mixed regulatory circuits (2012 update).
AB  - MAGIA(2) (http://gencomp.bio.unipd.it/magia2) is an update, extension and
      evolution of the MAGIA web tool. It is dedicated to the integrated analysis of in
      silico target prediction, microRNA (miRNA) and gene expression data for the
      reconstruction of post-transcriptional regulatory networks. miRNAs are
      fundamental post-transcriptional regulators of several key biological and
      pathological processes. As miRNAs act prevalently through target degradation,
      their expression profiles are expected to be inversely correlated to those of the
      target genes. Low specificity of target prediction algorithms makes integration
      approaches an interesting solution for target prediction refinement. MAGIA(2)
      performs this integrative approach supporting different association measures,
      multiple organisms and almost all target predictions algorithms. Nevertheless,
      miRNAs activity should be viewed as part of a more complex scenario where
      regulatory elements and their interactors generate a highly connected network and
      where gene expression profiles are the result of different levels of regulation.
      The updated MAGIA(2) tries to dissect this complexity by reconstructing mixed
      regulatory circuits involving either miRNA or transcription factor (TF) as
      regulators. Two types of circuits are identified: (i) a TF that regulates both a
      miRNA and its target and (ii) a miRNA that regulates both a TF and its target.

PMID- 22618882
TI  - A microporous-mesoporous carbon with graphitic structure for a high-rate stable
      sulfur cathode in carbonate solvent-based Li-S batteries.
AB  - A microporous-mesoporous carbon with graphitic structure was developed as a
      matrix for the sulfur cathode of a Li-S cell using a mixed carbonate electrolyte.
      Sulfur was selectively introduced into the carbon micropores by a melt adsorption
      solvent extraction strategy. The micropores act as solvent-restricted reactors
      for sulfur lithiation that promise long cycle stability. The mesopores remain
      unfilled and provide an ion migration pathway, while the graphitic structure
      contributes significantly to low-resistance electron transfer. The selective
      distribution of sulfur in micropores was characterized by X-ray photoelectron
      spectroscopy (XPS), nitrogen cryosorption analysis, transmission electron
      microscopy (TEM), X-ray powder diffraction and Raman spectroscopy. The high-rate
      stable lithiation-delithiation of the carbon-sulfur cathode was evaluated using
      galvanostatic charge-discharge tests, cyclic voltammetry and electrochemical
      impedance spectroscopy. The cathode is able to operate reversibly over 800 cycles
      with a 1.8 C discharge-recharge rate. This integration of a micropore reactor, a
      mesopore ion reservoir, and a graphitic electron conductor represents a
      generalized strategy to be adopted in research on advanced sulfur cathodes. 

PMID- 22618881
TI  - Abdominal obesity, weight gain during adulthood and risk of liver and biliary
      tract cancer in a European cohort.
AB  - General obesity has been positively associated with risk of liver and probably
      with biliary tract cancer, but little is known about abdominal obesity or weight
      gain during adulthood. We used multivariable Cox proportional hazard models to
      investigate associations between weight, body mass index, waist and hip
      circumference, waist-to-hip and waist-to-height ratio (WHtR), weight change
      during adulthood and risk of hepatocellular carcinoma (HCC), intrahepatic (IBDC)
      and extrahepatic bile duct system cancer [EBDSC including gallbladder cancer
      (GBC)] among 359,525 men and women in the European Prospective Investigation into
      Cancer and Nutrition study. Hepatitis B and C virus status was measured in a
      nested case-control subset. During a mean follow-up of 8.6 years, 177 cases of
      HCC, 58 cases of IBDC and 210 cases of EBDSC, including 76 cases of GBC,
      occurred. All anthropometric measures were positively associated with risk of HCC
      and GBC. WHtR showed the strongest association with HCC [relative risk (RR)
      comparing extreme tertiles 3.51, 95% confidence interval (95% CI): 2.09-5.87;
      p(trend)  < 0.0001] and with GBC (RR: 1.56, 95% CI: 1.12-2.16 for an increment of
      one unit in WHtR). Weight gain during adulthood was also positively associated
      with HCC when comparing extreme tertiles (RR: 2.48, 95% CI: 1.49-4.13; <0.001).
      No statistically significant association was observed between obesity and risk of
      IBDC and EBDSC. Our results provide evidence of an association between obesity,
      particularly abdominal obesity, and risk of HCC and GBC. Our findings support
      public health recommendations to reduce the prevalence of obesity and weight gain
      in adulthood for HCC and GBC prevention in Western populations.

PMID- 22618883
TI  - Is an immune reaction required for malignant transformation and cancer growth?
AB  - Increasing evidence has shown that probably all malignant mouse cells, even those
      of spontaneous sporadic cancers, are endowed with tumor-specific antigens.
      Stimulation of cancer growth, rather than inhibition by the immune reaction, is
      seemingly the prevalent effect in the animal of origin (the autochthonous
      animal). Small initial dosages of even strong tumor antigens tend to produce
      stimulatory immune reactions rather than tumor inhibition in any animal. Thus, an
      immune response at a low level may be an essential growth-driving feature of
      nascent cancers, and this may be why all cancers apparently have tumor-specific
      antigens. Inasmuch as a low level of immunity is stimulatory to tumor growth
      while larger dosages are inhibitory, immuno-selection via this low response may
      tend to keep the antitumor immune reaction weak and at a nearly maximal
      stimulatory level throughout most of a tumor's existence. These facts suggest
      that both suppression of tumor immunity and a heightened immune reaction might
      each be therapeutic although very contrasting modalities.

PMID- 22618884
TI  - Molecular subtype is determinant on inflammatory status and immunological profile
      from invasive breast cancer patients.
AB  - Breast cancer consists in a chronic inflammatory disease with multiple biological
      and clinical behaviors. Based on high throughput technologies data, this disease
      is currently classified according to the molecular expression of estrogen (ER),
      progesterone (PR) and human epidermal growth factor (HER-2) receptors. In this
      study, we defined the inflammatory profile of the main molecular subtypes of
      breast cancer patients: luminal (ER and PR positive, HER-2 negative), HER-2
      enriched (HER-2 positive) and triple negative (ER, PR and HER-2 negative).
      Cytokines panel was assessed by measurement of TNF-alpha, TGF-beta, IL-1, IL-10
      and IL-12 plasmatic levels. Oxidative profile was assessed by determination of
      lipid peroxidation, total antioxidant capacity of plasma, malondialdehyde levels,
      carbonyl content and nitric oxide (NO). Clinical data were correlated with
      inflammatory findings. Our findings demonstrated that patients bearing the
      luminal subtype displayed high TNF-alpha, TGF-beta and enhanced oxidative stress
      levels associated with reduced IL-12. HER-2-enriched group exhibited higher
      levels of TNF-alpha, IL-12 and TGF-beta associated with enhanced oxidative
      stress. Triple-negative subtype exhibited the most aggressive profile of disease
      behavior, with reduction in both TNF-alpha and TGF-beta, with high levels of
      lipid peroxidation and NO. The clinical importance of our findings lies in the
      fact that the inflammatory status varies in distinct ways due to molecular
      subtype of breast cancer, opening potential therapeutic targets to future
      therapies.

PMID- 22618885
TI  - Controllable self-assembly of organic-inorganic amphiphiles containing Dawson
      polyoxometalate clusters.
AB  - An organic-inorganic molecular hybrid containing the Dawson polyoxometalate,
      ((C(4)H(9))(4)N)(5)H[P(2)V(3)W(15)O(59)(OCH(2))(3)CNHCOC(15)H(31)], was
      synthesized and its surfactant-like amphiphilic properties, represented by the
      formation of bilayer vesicles, were studied in polar solvents. The vesicle size
      decreases with both decreasing hybrid concentration and with increasing polarity
      of the solvent, independently. The self-assembly behavior of this hybrid can be
      controlled by introducing different counterions into the acetonitrile solutions.
      The addition of ZnCl(2) and NaI can cause a gradual decrease and increase of
      vesicular sizes, respectively. Tetraalkylammonium bromide is found to disassemble
      the vesicle assemblies. Moreover, the original counterions of the hybrid can be
      replaced with protons, resulting in pH-dependent formation of vesicles in aqueous
      solutions. The hybrid surfactant can further form micro-needle structures in
      aqueous solutions upon addition of Ca(2+) ions.

PMID- 22618888
TI  - Photoswitched protein adsorption on electrostatically self-assembled azobenzene
      films.
AB  - Photoresponsive polymeric films fabricated by a facile electrostatic self
      assembly technique are utilized to switch protein adsorption by light
      irradiation. The introduction of SiO(2)  nanoparticles on the substrate results
      in a large reversible change of both wettability and protein adsorption.

PMID- 22618889
TI  - Comparison of diagnostic accuracy between three different rules of interpreting
      high sensitivity troponin T results.
AB  - With the introduction of high sensitivity troponin-T (hs-TnT) assay, clinicians
      face more patients with 'positive' results but without myocardial infarction.
      Repeated hs-TnT determinations are warranted to improve specificity. The aim of
      this study was to compare diagnostic accuracy of three different interpretation
      rules for two hs-TnT results taken 6 h apart. After adjusting for clinical
      differences, hs-TnT results were recoded according to the three rules. Rule1: hs
      TnT >13 ng/L in at least one determination. Rule2: change of >20 % between the
      two measures. Rule3: change >50 % if baseline hs-TnT 14-53 ng/L and >20 % if
      baseline >54 ng/L. The sensitivity, specificity and ROC curves were compared. The
      sensitivity analysis was used to generate post-test probability for any test
      result. Primary outcome was the evidence of coronary critical stenosis (CCS) on
      coronary angiography in patients with high-risk chest pain. 183 patients were
      analyzed (38.3 %) among all patients presenting with chest pain during the study
      period. CCS was found in 80 (43.7 %) cases. The specificity was 0.62 (0.52-0.71),
      0.76 (0.66-0.84) and 0.83 (0.74-0.89) for rules 1, 2 and 3, respectively (P <
      0.01). Sensitivity decreased with increasing specificity (P < 0.01). Overall
      diagnostic accuracy did not differ among the three rules (AUC curves difference P
      = 0.12). Sensitivity analysis showed a 25 % relative gain in predicting CCS using
      rule 3 compared to rule 1. Changes between two determinations of hs-TnT 6 h apart
      effectively improved specificity for CCS presence in high-risk chest pain
      patients. There was a parallel loss in sensitivity that discouraged any use of
      such changes as a unique way to interpret the new hs-TnT results.

PMID- 22618890
TI  - Effect of vitrification on promoter methylation and the expression of
      pluripotency and differentiation genes in mouse blastocysts.
AB  - The present study was designed to determine the effects of vitrification on
      promoter methylation and the expression levels of pluripotency and
      differentiation genes in mouse blastocysts. Promoter region CpG methylation
      patterns and the expression levels of octamer-binding transcription factor
      (Oct4), Nanog homeobox (Nanog), caudal-type homeobox 2 (Cdx2), and heart and
      neural crest derivatives-expressed transcript 1 (Hand1) were analyzed in fresh
      and vitrified mouse blastocysts. Methylation was measured by bisulphate
      mutagenesis and sequencing; gene expression was determined by real-time reverse
      transcription-PCR. The results showed that vitrification significantly reduced
      the methylation levels of the Oct4 (85% vs. 62.5%), Nanog (77.5% vs. 55%), and
      Cdx2 promoters (4.6% vs. 1.4%; P < 0.05) in mouse blastocysts, which correlated
      with increased expression of Oct4 and Nanog in vitrified blastocysts. Hand1
      promoter methylation was not significantly different in the fresh (17.9%) versus
      vitrification group (21.4%; P > 0.05). The expression levels of Cdx2 and Hand1
      were not significantly different in fresh and vitrified blastocysts. In
      conclusion, vitrification significantly decreased Oct4, Nanog, and Cdx2 promoter
      methylation in mouse blastocysts, which correlated with increased expression of
      Oct4 and Nanog.

PMID- 22618891
TI  - "It's like our own little world": resilience as a factor in participating in the
      Ballroom community subculture.
AB  - We are well into the third decade of the HIV epidemic. While strides have been
      made in HIV prevention, rates for African American men who have sex with men
      (AAMSM) and young AAMSM continue to increase-perhaps indicating that traditional
      deficit-approaches of HIV prevention are not effective for all populations.
      Following a recent call to investigate the resiliency of young gay men, this
      study identifies sources of resilience and strength within the House and Ball
      communities, a subculture comprised primarily of AAMSM. The mixed-methods design
      included survey data (N = 263) collected at community events, interviews with
      Ball attendees and focus group data with House members. Survey data indicate a
      relationship between participating in the House and Ball communities and seeking
      support, acceptance and entertainment. Qualitative data validate these findings
      and provide detail on motivations for AAMSM to participate and the perceived
      benefits of participation. Findings are discussed in relation to building
      strengths-based interventions, using concepts of resiliency including
      shamelessness, social creativity, social support and volunteerism.

PMID- 22618892
TI  - HIV incidence in young girls in KwaZulu-Natal, South Africa--public health
      imperative for their inclusion in HIV biomedical intervention trials.
AB  - Young women are particularly vulnerable for acquiring HIV yet they are often
      excluded from clinical trials testing new biomedical intervention. We assessed
      the HIV incidence and feasibility of enrolling a cohort of young women for
      potential participation in future clinical trials. Between March 2004 and May
      2007, 594 HIV uninfected 14-30 year old women were enrolled into a longitudinal
      HIV risk reduction study in KwaZulu-Natal, South Africa. The overall HIV
      prevalence at screening in young girls below the age of 18 years was 27.6 %
      compared to 52.0 % in the women above 18 years, p < 0.001. HIV incidence was 4.7
      [95 % Confidence interval (CI) 1.5-10.9) and 6.9 (95 % CI 4.8-9.6)/100 women
      years (wy), p = 0.42 and pregnancy rates were 23.7 (95 % CI 14.9-35.9) and 16.4
      (95 % CI 12.9-20.6)/100 wy, p = 0.29, in the women below and above 18 years
      respectively. Retention was similar in both groups (71.0 vs. 71.5 %, p = 0.90).
      This study demonstrates that the inclusion of young girls between the ages of 14
      and 17 years in longitudinal studies is feasible and their inclusion in clinical
      trials would maintain scientific integrity and power of the study.

PMID- 22618893
TI  - Relationship between vitamin D deficiency, bone remodelling and iron status in
      iron-deficient young women consuming an iron-fortified food.
AB  - BACKGROUND: Iron and vitamin D deficiencies are two of the most widespread
      nutritional disorders in the world. Our aim was to know whether the consumption
      of an iron-fortified fruit juice modifies bone remodelling and the possible
      influence of baseline vitamin D status on the recovery of iron status in a group
      of iron-deficient women. METHODS: Iron biomarkers, 25-hydroxyvitamin D levels and
      dietary intake were measured in 123 iron-deficient menstruating women. A subgroup
      (n = 41) participated in a randomised double-blind placebo-controlled study of 16
      weeks during winter. They consumed a placebo fruit juice (P) or iron-fortified
      fruit juice (F). Dietary intake, 25-hydroxyvitamin D, parathormone (PTH), bone
      alkaline phosphatase (ALP), aminoterminal telopeptide of collagen I (NTX) and
      iron biomarkers were determined. RESULTS: Ninety-two per cent of the iron
      deficient women were vitamin D deficient or insufficient. Transferrin saturation
      and 25-hydroxyvitamin D were positively correlated. Iron status improved in F, 25
      hydroxyvitamin D decreased in F and P, and PTH, ALP and NTX levels were within
      the normal range and did not vary. Women with 25-hydroxyvitamin D >= 50 nmol/L
      compared with 25-hydroxyvitamin D < 50 nmol/L showed a higher increase in
      transferrin saturation (a marker of iron supply to tissues) during iron recovery.
      CONCLUSION: The prevalence of vitamin D deficiency or insufficiency is very high
      in iron-deficient women. The recovery of iron status by consuming an iron
      fortified food does not affect 25-hydroxyvitamin D levels; however, the increase
      in iron supply to tissues is lower if the women also present vitamin D
      deficiency. Although bone health does not seem to be affected in this group of
      women, correction of iron and vitamin D deficiencies should be promoted in young
      women to improve present and future health.

PMID- 22618895
TI  - Vancomycin-resistant Enterococcus.
AB  - The reported prevalence of vancomycin-resistant Enterococcus faecium (VRE) in
      Switzerland for the years 2008-2010 has been low at <5%. At the University
      Hospital Zurich, 17 cases of VRE were detected between 28 December 2009 and 15
      February 2010. Nine cases were diagnosed clinically; eight cases were detected by
      rectal screening. The centre of the outbreak was the cardiac surgery department.
      Four patients suffered from VRE-infections; four patients died.  In order to
      investigate and contain the outbreak, the following measures were taken:
      prevalence surveys using weekly rectal screening, environmental screening;
      selective enrichment culturing; pulsed field gel electrophoresis (PFGE) for
      clonal typing and polymerase chain reaction-analysis (PCR) for resistance
      determinants and virulence factors detection. Contact isolation in single rooms
      and enhanced surface-disinfection methods were implemented. Ward nurses were
      assigned as link nurses. Regular teaching was carried out aiming to improve hand
      disinfection among healthcare workers.  PFGE revealed two main pulsotypes each
      including seven patients. Five minor pulsotypes originated from three additional
      patients and one sample collected from a keyboard. Two of three patients with
      minor pulsotypes had been treated abroad. PCR-analysis identified vanB resistance
      genotypes with exception of one vanA resistance-genotype. The outbreak was
      associated with environmental contamination and insufficient compliance with hand
      hygiene. Enhanced awareness and infection control measures resulted in
      termination of the VRE outbreak within eight weeks. The complexity of the
      outbreak with several clones in parallel suggests a higher baseline prevalence of
      VRE in Switzerland than previous surveillance data indicate.

PMID- 22618896
TI  - Genomic sequencing in newborn screening programs.

PMID- 22618894
TI  - Volumetric measurement of perfusion and arterial transit delay using hadamard
      encoded continuous arterial spin labeling.
AB  - Creating images of the transit delay from the labeling location to image tissue
      can aid the optimization and quantification of arterial spin labeling perfusion
      measurements and may provide diagnostic information independent of perfusion.
      Unfortunately, measuring transit delay requires acquiring a series of images with
      different labeling timing that adds to the time cost and increases the noise of
      the arterial spin labeling study. Here, we implement and evaluate a proposed
      Hadamard encoding of labeling that speeds the imaging and improves the signal-to
      noise ratio efficiency. Volumetric images in human volunteers confirmed the
      theoretical advantages of Hadamard encoding over sequential acquisition of images
      with multiple labeling timing. Perfusion images calculated from Hadamard encoded
      acquisition had reduced signal-to-noise ratio relative to a dedicated perfusion
      acquisition with either assumed or separately measured transit delays, however.

PMID- 22618900
TI  - The cover. The white wave.

PMID- 22618904
TI  - Rigorous evidence slim for determining health risks from natural gas fracking.

PMID- 22618905
TI  - Data on autism prevalence, trajectories illuminate socioeconomic disparities.

PMID- 22618906
TI  - Hepatitis drug reduces effects of HIV medications.

PMID- 22618911
TI  - Obesity in US children and adults.

PMID- 22618913
TI  - Genomic sequencing in newborn screening programs.

PMID- 22618914
TI  - Prevention of oral human papillomavirus infection.

PMID- 22618916
TI  - Changes to polymer surface of drug-eluting stents during balloon expansion.

PMID- 22618918
TI  - Retail clinics and drugstore medicine.

PMID- 22618920
TI  - Deciphering harm measurement.

PMID- 22618919
TI  - Assessing value in health care programs.

PMID- 22618921
TI  - The journey across the health care (dis)continuum for vulnerable patients:
      policies, pitfalls, and possibilities.

PMID- 22618922
TI  - A piece of my mind. Considering life before lifestyle.

PMID- 22618923
TI  - Effect of continuous positive airway pressure on the incidence of hypertension
      and cardiovascular events in nonsleepy patients with obstructive sleep apnea: a
      randomized controlled trial.
AB  - CONTEXT: Continuous positive airway pressure (CPAP) is the first-line treatment
      for patients with symptomatic obstructive sleep apnea (OSA). However, its
      indication for all patients with sleep-disordered breathing, regardless of
      daytime symptoms, is unclear. OBJECTIVE: To evaluate the effect of CPAP treatment
      on the incidence of hypertension or cardiovascular events in a cohort of
      nonsleepy patients with OSA. DESIGN, SETTING, AND PATIENTS: Multicenter, parallel
      group, randomized controlled trial in 14 teaching hospitals in Spain. Between May
      2004 and May 2006, 725 consecutive patients were enrolled who had an apnea
      hypopnea index of 20 h(-1) or greater and an Epworth Sleepiness Scale score of 10
      or less (scores range from 0-24, with values <10 suggesting no daytime
      sleepiness). Exclusion criteria were previous cardiovascular event, physical or
      psychological incapacity, chronic disease, or drug or alcohol addiction. Follow
      up ended in May 2009. INTERVENTION: Patients were allocated to receive CPAP
      treatment or no active intervention. All participants received dietary counseling
      and sleep hygiene advice. MAIN OUTCOME MEASURES: Incidence of either systemic
      hypertension (taking antihypertensive medication or blood pressure greater than
      140/90 mm Hg) or cardiovascular event (nonfatal myocardial infarction, nonfatal
      stroke, transient ischemic attack, hospitalization for unstable angina or
      arrhythmia, heart failure, or cardiovascular death). RESULTS: Seven hundred
      twenty-three patients underwent follow-up for a median of 4 (interquartile range,
      2.7-4.4) years (1 patient from each group did not receive allocated treatment);
      357 in the CPAP group and 366 in the control group were included in the analysis.
      In the CPAP group there were 68 patients with new hypertension and 28
      cardiovascular events (17 unstable angina or arrhythmia, 3 nonfatal stroke, 3
      heart failure, 2 nonfatal myocardial infarction, 2 transient ischemic attack, 1
      cardiovascular death). In the control group there were 79 patients with new
      hypertension and 31 cardiovascular events (11 unstable angina or arrhythmia, 8
      nonfatal myocardial infarction, 5 transient ischemic attack, 5 heart failure, 2
      nonfatal stroke). The hypertension or cardiovascular event incidence density rate
      was 9.20 per 100 person-years (95% CI, 7.36-11.04) in the CPAP group and 11.02
      per 100 person-years (95% CI, 8.96-13.08) in the control group. The incidence
      density ratio was 0.83 (95% CI, 0.63-1.1; P = .20). CONCLUSIONS: In patients with
      OSA without daytime sleepiness, the prescription of CPAP compared with usual care
      did not result in a statistically significant reduction in the incidence of
      hypertension or cardiovascular events. However, the study may have had limited
      power to detect a significant difference. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00127348.

PMID- 22618924
TI  - Association between treated and untreated obstructive sleep apnea and risk of
      hypertension.
AB  - CONTEXT: Systemic hypertension is prevalent among patients with obstructive sleep
      apnea (OSA). Short-term studies indicate that continuous positive airway pressure
      (CPAP) therapy reduces blood pressure in patients with hypertension and OSA.
      OBJECTIVE: To determine whether CPAP therapy is associated with a lower risk of
      incident hypertension. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort
      study of 1889 participants without hypertension who were referred to a sleep
      center in Zaragoza, Spain, for nocturnal polysomnography between January 1, 1994,
      and December 31, 2000. Incident hypertension was documented at annual follow-up
      visits up to January 1, 2011. Multivariable models adjusted for confounding
      factors, including change in body mass index from baseline to censored time, were
      used to calculate hazard ratios (HRs) of incident hypertension in participants
      without OSA (controls), with untreated OSA, and in those treated with CPAP
      therapy according to national guidelines. MAIN OUTCOME MEASURE: Incidence of new
      onset hypertension. RESULTS: During 21,003 person-years of follow-up (median,
      12.2 years), 705 cases (37.3%) of incident hypertension were observed. The crude
      incidence of hypertension per 100 person-years was 2.19 (95% CI, 1.71-2.67) in
      controls, 3.34 (95% CI, 2.85-3.82) in patients with OSA ineligible for CPAP
      therapy, 5.84 (95% CI, 4.82-6.86) in patients with OSA who declined CPAP therapy,
      5.12 (95% CI, 3.76-6.47) in patients with OSA nonadherent to CPAP therapy, and
      3.06 (95% CI, 2.70-3.41) in patients with OSA and treated with CPAP therapy.
      Compared with controls, the adjusted HRs for incident hypertension were greater
      among patients with OSA ineligible for CPAP therapy (1.33; 95% CI, 1.01-1.75),
      among those who declined CPAP therapy (1.96; 95% CI, 1.44-2.66), and among those
      nonadherent to CPAP therapy (1.78; 95% CI, 1.23-2.58), whereas the HR was lower
      in patients with OSA who were treated with CPAP therapy (0.71; 95% CI, 0.53
      0.94). CONCLUSION: Compared with participants without OSA, the presence of OSA
      was associated with increased adjusted risk of incident hypertension; however,
      treatment with CPAP therapy was associated with a lower risk of hypertension.

PMID- 22618925
TI  - Effect of a guideline-based multicomponent intervention on use of physical
      restraints in nursing homes: a randomized controlled trial.
AB  - CONTEXT: Despite unambiguous legal regulation and evidence for lack of
      effectiveness and safety, physical restraints are still frequently administered
      in nursing homes. OBJECTIVE: To reduce physical restraint prevalence in nursing
      homes using a guideline- and theory-based multicomponent intervention. DESIGN,
      SETTING, AND PARTICIPANTS: Cluster randomized controlled trial of 6 months'
      duration conducted in 2 German cities between February 2009 and April 2010.
      Nursing homes were eligible if they had 20% or more residents with physical
      restraints. Using external concealed randomization, 18 nursing home clusters were
      included in the intervention group (2283 residents) and 18 in the control group
      (2166 residents). INTERVENTION: The intervention was based on a specifically
      developed evidence-based guideline and applied the theory of planned behavior.
      Components were group sessions for all nursing staff; additional training for
      nominated key nurses; and supportive material for nurses, residents, relatives,
      and legal guardians. Control group clusters received standard information. MAIN
      OUTCOMES MEASURES: Primary outcome was percentage of residents with physical
      restraints (bilateral bed rails, belts, fixed tables, and other measures limiting
      free body movement) at 6 months, assessed through direct unannounced observation
      by blinded investigators on 3 occasions during 1 day. Secondary outcomes included
      restraint use at 3 months, falls, fall-related fractures, and psychotropic
      medication prescriptions. RESULTS: All nursing homes completed the study and all
      residents were included in the analysis. At baseline, 30.6% of control group
      residents had physical restraints vs 31.5% of intervention group residents. At 6
      months, rates were 29.1% vs 22.6%, respectively, a difference of 6.5% (95% CI,
      0.6% to 12.4%; cluster-adjusted odds ratio, 0.71; 95% CI, 0.52 to 0.97; P = .03).
      All physical restraint measures were used less frequently in the intervention
      group. Rates were stable from 3 to 6 months. There were no statistically
      significant differences in falls, fall-related fractures, and psychotropic
      medication prescriptions. CONCLUSION: A guideline- and theory-based
      multicomponent intervention compared with standard information reduced physical
      restraint use in nursing homes. TRIAL REGISTRATION: isrctn.org Identifier:
      ISRCTN34974819.

PMID- 22618926
TI  - Hip fracture management: tailoring care for the older patient.
AB  - Hip fracture is a potentially devastating condition for older adults. Hip
      fracture leads to pain and immobilization with complications ranging from
      delirium to functional loss and death. Although a mainstay of treatment is
      orthopedic repair, a multidisciplinary comanagement approach, including medical
      specialists and rehabilitation, may maximize patient recovery. Using the case of
      Mr W, an older man who sustained a fall and hip fracture, we present evidence
      based components of care both in the hospital and outpatient settings.
      Preoperatively, clinicians should correct medical abnormalities and consider the
      appropriateness, timing, and type of surgical repair in the context of the
      patient's life expectancy and goals of care. Perioperative care should include
      prophylaxis with antibiotics, chemoprophylaxis for venous thromboembolism, and
      correction of major clinical abnormalities prior to surgery. Pain control,
      delirium, and pressure ulcer prevention are important inpatient care elements.
      Multidisciplinary models incorporating these care elements can decrease
      complications during inpatient stay. Rehabilitation strategies should be tailored
      to patient needs; early mobilization followed by rehabilitation exercises in
      institutional, home, and group settings should be considered to maximize
      restoration of locomotive abilities. Attention to care transitions is necessary
      and treatment for osteoporosis should be considered. The road to recovery for hip
      fracture patients is long and most patients may not regain their prefracture
      functional status. Understanding and anticipating issues that may arise in the
      older patient with hip fracture, while delivering evidence-based care components,
      is necessary to maximize patient recovery.

PMID- 22618927
TI  - Progressive confusion, memory loss, and gait ataxia in an adult.

PMID- 22618928
TI  - Filling in the pieces of the sleep apnea-hypertension puzzle.

PMID- 22618932
TI  - JAMA patient page. Interstitial cystitis.

PMID- 22618951
TI  - A case of a patient who experienced diaphragmatic hernia after repair of inguinal
      hernia.

PMID- 22618952
TI  - Effects of TrkA inhibitory peptide on cancer-induced pain in a mouse melanoma
      model.
AB  - PURPOSE: Tropomyosin receptor kinase (Trk) A, a high-affinity receptor of nerve
      growth factor, is a therapeutic target for both noxious and neuropathic pain. The
      present study examined the effects of an inhibitory peptide of Trk activity
      (IPTRK) 3 that inhibits TrkA activity on cancer-induced pain in a mouse melanoma
      model. METHODS: The hind paws of mice were inoculated with B16-F1 mouse melanoma
      cells on day 0. We administered IPTRK3 (20 mg/kg i.p.) repetitively on days 5, 6,
      7, 8, and 9, and evaluated pain-related behaviors on days 0, 5, 10, 15, and 20
      after tumor inoculation. RESULTS: Following inoculation, mice demonstrated
      mechanical allodynia and thermal hyperalgesia with an increased number of
      flinches, and paw volume increased gradually. However, an intraperitoneal
      injection of IPTRK3 significantly inhibited mechanical allodynia on day 15 and
      suppressed the number of flinches on day 20. The increased paw volume was
      significantly suppressed on day 20 after tumor inoculation. IPTRK3, however,
      showed no significant effect on thermal hyperalgesia. CONCLUSIONS: These results
      suggest that TrkA inhibitory peptide likely suppress melanoma-induced pain with
      concomitant reduction in the increased paw volume in a mouse skin cancer pain
      model.

PMID- 22618953
TI  - Extracorporeal membrane oxygenation for 2009 influenza A(H1N1) severe respiratory
      failure in Japan.
AB  - PURPOSE: To evaluate procedures and outcomes of extracorporeal membrane
      oxygenation (ECMO) therapy applied to 2009 influenza A(H1N1) severe respiratory
      failure patients in Japan. METHODS: This observational study used database
      information about adults who received ECMO therapy for H1N1-related severe
      respiratory failure from April 1, 2010 to March 31, 2011. RESULTS: Fourteen
      patients from 12 facilities were enrolled. Anti-influenza drugs were used in all
      cases. Before the start of ECMO, the lowest PaO(2)/FiO(2) was median
      (interquartile) of 50 (40-55) mmHg, the highest peak inspiratory pressure was 30
      (29-35) cmH(2)O, and mechanical ventilation had been applied for at least 7 days
      in 5 patients. None of the facilities had extensive experience with ECMO for
      respiratory failure (6 facilities, no previous experience; 5 facilities, one or
      two cases annually). The blood drainage cannula was smaller than 20 Fr. in 10
      patients (71.4 %). The duration of ECMO was 8.5 (4.0-10.8) days. The duration of
      each circuit was only 4.0 (3.2-5.3) days, and the ECMO circuit had to be renewed
      19 times (10 cases). Thirteen patients (92.9 %) developed adverse events
      associated with ECMO, such as oxygenator failure, massive bleeding, and
      disseminated intravascular coagulation. The survival rate was 35.7 % (5
      patients). CONCLUSION: ECMO therapy for H1N1-related severe respiratory failure
      in Japan has very poor outcomes, and most patients developed adverse events.
      However, this result does not refute the effectiveness of ECMO. One possible
      cause of these poor outcomes is the lack of satisfactory equipment, therapeutic
      guidelines, and systems for patient transfer to central facilities.

PMID- 22618954
TI  - Ribosome readthrough accounts for secreted full-length factor IX in hemophilia B
      patients with nonsense mutations.
AB  - We investigated the spontaneous ribosome readthrough, virtually unexplored in
      genes encoding secreted proteins, over coagulation F9 nonsense mutations.
      Expression of recombinant factor IX (FIX) in eukaryotic cells demonstrated
      appreciable levels of secreted FIX molecules for the mutations p.R162* (5 +/-
      0.3% of rFIX-wt antigen levels), p.R294* (3.1 +/- 1.1%) and p.R298* (2.5 +/-
      0.7%), but not for the p.L103*. Western blotting revealed a large proportion of
      truncated molecules, which correlated with small amounts of full-length FIX (rFIX
      162*, ~0.5%; rFIX-294*; and rFIX-298*, ~0.2%). Western blotting of plasma from
      FIX deficient (Hemophilia B) patients revealed traces of full-length FIX for the
      p.R294* and p.R298* mutations, but not for the p.L103* mutation that triggered
      major FIX mRNA decay. The detection of full-length proteins has clinical
      implication, particularly for post-therapeutic immunological complications in
      Hemophilia. Data in patients' plasma and in vitro, obtained in the proper protein
      context, support a ribosome readthrough gradient, consistent with its predicted
      determinants of efficiency.

PMID- 22618955
TI  - Desensitization treatment for hypersensitivity reaction to octreotide in an
      acromegalic patient.
AB  - Octreotide is widely used as medical therapy for acromegaly. It is known to
      markedly reduce growth hormone levels, improve symptoms and reduce tumor size.
      Common side effects include gastrointestinal symptoms, hepatobiliary disorders,
      dizziness, headaches, bradycardia, hyperglycemia or hypoglycemia and thyroid
      dysfunction. Although urticaria, allergy/hypersensitivity reactions and
      anaphylaxis have been noted as possible adverse reactions, there is a lack of
      data showing a causal relationship between octreotide and hypersensitivity
      reactions and there is no information on management when continued use of this
      medication is essential. We now report a case of a 60 year old male with
      acromegaly who had presented with a cutaneous hypersensitivity reaction to
      octreotide. In addition he failed treatment with surgery, radiation, and dopamine
      agonist and could no longer afford to continue treatment with pegvisomant. The
      patient underwent desensitization treatment for his octreotide allergy and was
      able to resume treatment without any further side effects. We believe this case
      represents the first report of successful desensitization treatment for
      octreotide allergy in an acromegalic patient.

PMID- 22618957
TI  - Fighting stigma of mental illness in midsize European countries.

PMID- 22618956
TI  - Effect of triclosan-coated sutures on the incidence of surgical wound infection
      after lower limb revascularization surgery: a randomized controlled trial.
AB  - BACKGROUND: Surgical wound infection (SWI) is a common complication after
      peripheral vascular surgery. In a prospective study, triclosan-coated sutures
      were reported to decrease the incidence of surgical site infection after various
      surgical procedures. The aim of our study was to test the hypothesis that use of
      triclosan-coated sutures decreases the incidence of SWI after lower limb vascular
      surgery. METHODS: This prospective, randomized, multicenter, double-blinded trial
      was conducted between July 2010 and January 2011 in five hospitals in Finland. We
      randomly allocated 276 patients undergoing lower limb revascularization surgery
      to a study (n = 139) or a control (n = 137) group. Surgical wounds in the study
      group were closed with triclosan-coated suture material, and wounds in the
      control group were closed with noncoated sutures. The main outcome measure was
      SWI. A surgical wound complication was considered to be an infection if there
      were bacteria isolated from the wound or if there were areas of localized
      redness, heat, swelling, and pain around the wound appearing within 30 days after
      the operative procedure. Logistic regression analysis was used to assess the
      independent effect of triclosan-coated sutures on the incidence of SWI. RESULTS:
      Altogether, 61 (22.1 %) patients developed SWI. SWI occurred in 31 (22.3 %)
      patients in the study group and in 30 (21.9 %) patients in the control group
      (odds ratio 1.10, 95% confidence interval 0.61-2.01, p = 0.75.) CONCLUSIONS: The
      use of triclosan-coated sutures does not reduce the incidence of SWI after lower
      limb vascular surgery.

PMID- 22618958
TI  - Incidence and trends in Burkitt lymphoma in northern Tanzania from 2000 to 2009.
AB  - INTRODUCTION: Burkitt lymphoma (BL) is endemic in parts of Tanzania, but there is
      scant country or region level data about burden and trends of BL in Tanzania over
      the past three decades. Here, we update baseline epidemiology of BL in northern
      Tanzania using recent data. PROCEDURE: Data for childhood BL diagnosed at six
      hospitals in Mara and Mwanza regions in northern Tanzania during 2000-2009 were
      compiled. Age, sex, and regional patterns were analyzed. Crude incidence rates of
      BL were calculated by sex, anatomic site, geographical region, and calendar year.
      RESULTS: Among 944 cases, 549 (58%) were male (male/female case ratio 1.4:1).
      Among those with known anatomic site (92%), facial only tumors represented a
      large proportion of tumors in boys than girls (50% vs. 36%, P < 0.002). Tumors
      occurred at a younger mean age in boys than girls (6.8 years vs. 7.6 years, P <
      0.01). Crude BL incidence was 4.2 per 100,000, but varied by region (3.0 in
      Mwanza vs. 6.8 in Mara, P = 0.01), by district (1.4-22), by gender (5.0 in boys
      vs. 4.0 in girls), and by age group (2.0 in 0-4, 7.8 in 5-9, and 3.1 in 10-15
      years). BL incidence peaked in 2001 and decreased gradually thereafter.
      CONCLUSIONS: Our results indicate that male sex, young age, and geographical
      characteristics are risk factors for BL in Tanzania. BL incidence declined with
      calendar year, but the significance of this finding is uncertain. Well-designed
      epidemiological studies of BL in Tanzania may shed light on environmental
      characteristics underlying these patterns.

PMID- 22618959
TI  - Expression and phylogeny of candidate genes for sex differentiation in a
      primitive fish species, the Siberian sturgeon, Acipenser baerii.
AB  - The molecular mechanisms underlying testis differentiation in basal
      actinopterygian fish remains poorly understood. The sex differentiation period
      was investigated in the Siberian sturgeon, Acipenser baerii, by expression
      profiling of Sertoli cell transcription factors (dmrt1, sox9) that control testis
      differentiation in vertebrates; Leydig cell factors (cyp17a1, star) affecting
      androgen production; the androgen receptor (ar); a growth factor controlling
      testis development (igf1); and a gene coding for a gonadotropin hormone (lh). Two
      genes were characterised for the first time in the Siberian sturgeon (dmrt1,
      cyp17a1), while the others came from public databases. Sturgeon gonad development
      is very slow, with a late sexual differentiation time during their juvenile
      stage, and are still immature at 3 years of age. Immature fish showed a sex
      dimorphic pattern; all the genes studied displayed a higher expression level in
      male gonads. We took advantage of the presence of juvenile fish with pre- and
      post-differentiated gonads (16 and 18 months old) to characterise them at the
      molecular level. The post-differentiated fish displayed a sex dimorphism of gene
      expression in their gonads for all genes studied, with the exception of sox9. The
      trends in undifferentiated fish lead us to propose that sturgeons undergoing male
      differentiation express high levels of Sertoli cell factors (dmrt1, sox9) and of
      genes involved in the production and receptivity of androgens (cyp17a1, star and
      ar) together with lh. Expression profiles and phylogenetic studies suggest that
      these genes are potential regulators of testis development in the Siberian
      sturgeon.

PMID- 22618960
TI  - Influence of the molecular structure and morphology of self-assembled 1,3,5
      benzenetrisamide nanofibers on their mechanical properties.
AB  - The influence of molecular structure on the mechanical properties of self
      assembled 1,3,5-benzenetrisamide nanofibers is investigated. Three compounds with
      different amide connectivity and different alkyl substituents are compared. All
      the trisamides form well-defined fibers and exhibit significant differences in
      diameters of up to one order of magnitude. Using nanomechanical bending
      experiments, the rigidity of the nanofibers shows a difference of up to three
      orders of magnitude. Calculation of Young's modulus reveals that these
      differences are a size effect and that the moduli of all systems are similar and
      in the lower GPa range. This demonstrates that variation of the molecular
      structure allows changing of the fibers' morphology, whereas it has a minor
      influence on their modulus. Consequently, the stiffness of the self-assembled
      nanofibers can be tuned over a wide range--a crucial property for applications as
      versatile nano- and micromechanical components.

PMID- 22618961
TI  - Pneuma-fire interactions in Hippocratic physiology.
AB  - Hippocratic treatises written in the late fifth and early fourth centuries BCE
      contain some of the earliest conjectures known concerning the physiological roles
      of the pneuma, or "breath," that was supposed to be involved in various functions
      within human and animal bodies. A cross-referenced survey of these texts suggests
      that the contemporary theories on the subject may have gone far beyond the well
      known attribution of epilepsy and other diseases to disorders in the flow of
      pneuma within the vessels. A pattern of co-dependent interplay between air-pneuma
      and fire-heat is evident among the different sources, despite disagreements of
      the authors on general outlook and other matters. The mutual engagement of those
      two elements, in turn, is found woven into elaborate mechanisms to explain, with
      a cause-to-effect approach, vital processes such as the regulation of body
      temperature through respiration, embryonic growth through morphogenetic
      differentiation, and even plant germination. Viewed in a historical context,
      these features suggest that Hippocratic speculation about pneuma may be
      representative of a conceptual bridging step, i.e., a stage intermediate between
      some seminal precedents of Presocratic thought and the more mature Aristotelian
      and Hellenistic theories. 

PMID- 22618962
TI  - Evaluation of data quality at the Gambia national cancer registry.
AB  - The Gambia National Cancer Registry (GNCR) is one of the few nationwide
      population-based cancer registries in sub-Saharan Africa. Most registries in sub
      Saharan Africa are limited to cities; therefore, the GNCR is important in
      providing estimates of cancer incidence in rural Africa. Our study assesses the
      quality of its data. The methods proposed by Bray and Parkin, and Parkin and Bray
      (Eur J Cancer 2009;45:747-64) were applied to the registry data from 1990 to 2009
      to assess comparability, validity and completeness. The system used for
      classification and coding of neoplasms followed international standards. The
      percentage of cases morphologically verified was 18.1% for men and 33.1% for
      women, and that of death certificate only cases was 6.6 and 3.6%, respectively.
      Incidence rates in rural regions were lower than in the urban part of the
      country, except amongst young male adults. Comparison with other West African
      registries showed that the incidences of liver and uterine cervical cancer were
      comparable, but those of prostate and breast in The Gambia were relatively low.
      The overall completeness was estimated at 50.3% using the capture-recapture
      method. The GNCR applies international standard practices to data collection and
      handling, providing valuable data on cancer incidence in sub-Saharan Africa.
      However, the data are incomplete in the rural and elderly populations probably
      because of health care access and use.

PMID- 22618963
TI  - Moderation and mediation of an effective HIV risk-reduction intervention for
      South African adolescents.
AB  - BACKGROUND: "Let Us Protect Our Future" is a sexual risk-reduction intervention
      for sixth-grade adolescents in South Africa. Tested in a cluster-randomized
      controlled trial, the intervention significantly reduced self-reported
      intercourse and unprotected intercourse during a 12-month follow-up period.
      PURPOSE: The present analyses were conducted to identify moderators of the
      intervention's efficacy as well as, which theory-based variables mediated the
      intervention's effects. METHODS: Intervention efficacy over the 3-, 6-, and 12
      month follow-up was tested using generalized estimating equation models. RESULTS:
      Living with their father in the home, parental strictness, and religiosity
      moderated the efficacy of the intervention in reducing unprotected intercourse.
      Self-efficacy to avoid risky situations and expected parental disapproval of
      their having intercourse, derived from Social Cognitive Theory, significantly
      mediated the intervention's effect on abstinence. CONCLUSIONS: This is the first
      study to demonstrate that Social Cognitive variables mediate the efficacy of a
      sexual risk-reduction intervention among South African adolescents.

PMID- 22618964
TI  - Soft constraints in nonlinear spectral fitting with regularized lineshape
      deconvolution.
AB  - This article presents a novel method for incorporating a priori knowledge into
      regularized nonlinear spectral fitting as soft constraints. Regularization was
      recently introduced to lineshape deconvolution as a method for correcting
      spectral distortions. Here, the deconvoluted lineshape was described by a new
      type of lineshape model and applied to spectral fitting. The nonlinear spectral
      fitting was carried out in two steps that were subject to hard constraints and
      soft constraints, respectively. The hard constraints step provided a starting
      point and, therefore, only the changes of the relevant variables were constrained
      in the soft constraints step and incorporated into the linear substeps of the
      Levenberg-Marquardt algorithm. The method was demonstrated using localized
      averaged echo time point resolved spectroscopy proton spectroscopy of human
      brains.

PMID- 22618965
TI  - Tailor-made metal-organic frameworks from functionalized molecular building
      blocks and length-adjustable organic linkers by stepwise synthesis.
AB  - In this work, we have demonstrated a family of diamondoid metal-organic
      frameworks (MOFs) based on functionalized molecular building blocks and length
      adjustable organic linkers by using a stepwise synthesis strategy. We have
      successfully achieved not only "design" and "control" to synthesize MOFs, but
      also the functionalization of both secondary building units (SBUs) and organic
      linkers in the same MOF for the first time. Furthermore, the results of N(2)  and
      H(2)  adsorption show that their surface areas and hydrogen uptake capacities are
      determined by the most optimal combination of functional groups from SBUs and
      organic linkers, interpenetration, and free volume in this system. A member of
      this series, DMOF-6 exhibits the highest surface area and H(2)  adsorption
      capacity among this family of MOFs.

PMID- 22618966
TI  - Right diaphragmatic defect in hepatic hydrothorax exposed by contrast-enhanced
      ultrasonography after radiofrequency ablation.
AB  - A 68-year-old male with liver cirrhosis and hepatocellular carcinoma treated by
      radiofrequency ablation was hospitalized for right hepatic hydrothorax and
      ascites. Perflubutane injected into the peritoneal cavity after an
      ultrasonography contrast agent revealed jet-like flow from the ascites to a
      pleural effusion, indicating a diaphragmatic defect. A hepatic hydrothorax was
      sutured under thoracoscopy and did not recur. An intraperitoneal injection of
      perflubutane enables a less-invasive diagnosis of a diaphragmatic defect.

PMID- 22618967
TI  - Narrow genetic basis for the Australian dingo confirmed through analysis of
      paternal ancestry.
AB  - The dingo (Canis lupus dingo) is an iconic animal in the native culture of
      Australia, but archaeological and molecular records indicate a relatively recent
      history on the continent. Studies of mitochondrial DNA (mtDNA) imply that the
      current dingo population was founded by a small population of already tamed dogs
      from Southeast Asia. However, the maternal genetic data might give a unilateral
      picture, and the gene pool has yet to be screened for paternal ancestry. We
      sequenced 14,437 bp of the Y-chromosome (Y-chr) from two dingoes and one New
      Guinea Singing Dog (NGSD). This positioned dingo and NGSD within the domestic dog
      Y-chr phylogeny, and produced one haplotype not detected before. With this data,
      we characterized 47 male dingoes in 30 Y-chr single-nucleotide polymorphism sites
      using protease-mediated allele-specific extension technology. Only two
      haplotypes, H3 and H60, were found among the dingoes, at frequencies of 68.1 and
      31.9 %, respectively, compared to 27 haplotypes previously established in the
      domestic dog. While H3 is common among Southeast Asian dogs, H60 was specifically
      found in dingoes and the NGSD, but was related to Southeast Asian dog Y-chr
      haplotypes. H3 and H60 were observed exclusively in the western and eastern parts
      of Australia, respectively, but had a common range in Southeast. Thus, the Y-chr
      diversity was very low, similar to previous observations for d-loop mtDNA.
      Overall genetic evidence suggests a very restricted introduction of the first
      dingoes into Australia, possibly from New Guinea. This study further confirms the
      dingo as an isolated feral dog.

PMID- 22618968
TI  - Vancomycin-resistant enterococci: an ongoing challenge for infection control.

PMID- 22618969
TI  - Evaluation of continuing professional development portfolios for pharmacist
      license renewal.

PMID- 22618970
TI  - Electronic prescribing errors: do they exist?

PMID- 22618971
TI  - Leadership development: empowering others to take an active role in patient care.

PMID- 22618972
TI  - Development of the Consumer Assessment of Pharmacy Services survey.
AB  - OBJECTIVES: To develop and test a tool for obtaining patient evaluations of the
      quality of pharmacy services provided in ambulatory settings. DESIGN:
      Descriptive, exploratory, nonexperimental study. SETTING: United States from June
      1, 2006, through May 31, 2007. PARTICIPANTS: 895 individuals who obtained
      prescription medications from participating pharmacies. INTERVENTION: Items were
      evaluated for inclusion in composite scales based on factor analysis and
      frequency of missing data. Standard psychometric methods were used to assess the
      reliability and construct validity of the resulting three composite and three
      global-item measures. MAIN OUTCOME MEASURE: Patient assessment of the quality of
      ambulatory care pharmacy services. RESULTS: Confirmatory factor analysis
      indicated that a subset of 15 items measuring three aspects of pharmacy services
      (General Staff Communication, Health- and Medication-Focused Communication, and
      Clarity of Written Information about Medications) provided excellent fit to the
      data. Cronbach's alphas for these scales were greater than 0.80. The three scales
      and corresponding three global ratings of quality reliably described differences
      among providers of pharmacy services. CONCLUSION: These data provide support for
      the reliability and validity of the Consumer Assessment of Pharmacy Services
      survey. Although preliminary results regarding reliability and validity are
      promising, further study of the survey is warranted.

PMID- 22618973
TI  - Patient desire to be involved in medication treatment decisions.
AB  - OBJECTIVES: To identify unmet needs of patients taking medications for chronic
      health conditions and identify medication-related services that patients with
      chronic health conditions would desire. DESIGN: Descriptive, exploratory,
      nonexperimental study. SETTING: Large midwestern state in spring 2010.
      PARTICIPANTS: 465 patients 45 years or older taking one or more prescriptions for
      chronic health problems. INTERVENTION: Cross-sectional survey. MAIN OUTCOME
      MEASURES: Patient-reported usefulness of, satisfaction with, and intention to use
      medication-related services. RESULTS: Respondents wanted to be highly involved in
      treatment decisions but found medication information they received to be
      moderately useful and satisfactory. Medication-related services fell into three
      groups based on reported intention to use: therapy advice, cost advice, and
      medication organization. Desire to be involved in treatment decisions was a key
      factor in predicting reported intention to use therapy advice and cost advice
      services. The perceived affordability of medications was another important factor
      in patients' intention to use cost advice and medication organization services.
      Age, chronic conditions, number of prescription drugs, and the cost of therapy
      were not important in predicting the intention to use medication-related services
      in this population. CONCLUSION: Patient desire to be involved in treatment
      decisions was a key factor in explaining intention to use medication-related
      services. Identifying individuals with desire for involvement in treatment
      decisions may increase medication therapy management (MTM) participation.
      Strategies to provide personalized MTM services to these individuals should be
      developed and evaluated.

PMID- 22618974
TI  - Relationship between availability of contraceptive products and pharmacists as
      information sources.
AB  - OBJECTIVE: To describe the relationship between the availability and
      accessibility of contraceptives in Iowa pharmacies and the extent to which
      pharmacists act as an information source regarding contraceptives. DESIGN:
      Descriptive, exploratory, nonexperimental study. SETTING: Iowa in fall 2008.
      PARTICIPANTS: 282 pharmacists at Iowa community pharmacies. INTERVENTION: Cross
      sectional survey. MAIN OUTCOME MEASURES: Contraceptive availability score,
      contraceptive accessibility score, and total access score. Regression analyses
      tested the relationships between the pharmacist information source score and the
      contraceptive availability, accessibility, and total access scores, controlling
      for geography, ownership, staff size, and average number of prescriptions per
      day. RESULTS: Significant positive relationships between the pharmacist
      information source score and product accessibility, product availability, and
      total access were observed. The relationship appeared to be driven primarily by
      product availability, and all were significantly influenced by pharmacy type.
      Significant negative relationships were found between product accessibility and
      independent/small chain pharmacies and mass merchandiser/grocery store pharmacies
      relative to large chain pharmacies. A significant negative relationship was found
      between independent/small chain pharmacies and the product availability score.
      CONCLUSION: Significant relationships were found between pharmacists' ability to
      act as sources of information for contraceptive products and the availability,
      accessibility, and overall access to contraceptives in the pharmacy.

PMID- 22618975
TI  - Low-income women's access to contraception after health care reform in
      Massachusetts.
AB  - OBJECTIVES: To determine the experiences of low-income women who were eligible
      for government-subsidized health insurance and seeking contraception in community
      pharmacies following health care reform (HCR) in Massachusetts, to investigate
      the transitions experienced by family planning providers following HCR, and to
      evaluate the availability and ease of navigation of information on the
      Commonwealth Care plans websites regarding prescription benefits, including
      contraceptive formularies and copays. DESIGN: Descriptive, exploratory,
      nonexperimental study. SETTING: Massachusetts between August 2008 and March 2009.
      PARTICIPANTS: Family planning agency and site staff (n = 16) at 15 sites and low
      income (<300% federal poverty level) English- and Spanish-speaking women (n = 23
      and 29, respectively). INTERVENTION: Commonwealth Care (i.e., government
      subsidized insurance plans for low-income residents) websites were reviewed,
      family planning agency administrators were surveyed, family planning staff were
      interviewed, and focus groups were conducted among low-income women. MAIN OUTCOME
      MEASURES: Experiences of low-income women and family planning providers. RESULTS:
      Findings from all study components were highly consistent. After reform, family
      planning staff reported providing more prescriptions for contraception versus
      providing contraception on site. Many focus group participants and family
      planning providers felt pharmacy provision of contraception enhanced access as a
      result of the convenient location of pharmacies. New barriers to obtaining
      contraception included an inability to obtain more than 1 month of contraception
      at a time and lack of coverage for over-the-counter methods. Findings about
      changes in the affordability of contraception postreform were mixed. CONCLUSION:
      HCR in Massachusetts changed how low-income women access contraception,
      presenting new opportunities and challenges for women, family planning providers,
      and pharmacists. The results of this project provide valuable lessons for
      pharmacists around the country as national HCR is implemented.

PMID- 22618976
TI  - Postdischarge interventions by pharmacists and impact on hospital readmission
      rates.
AB  - OBJECTIVES: To determine whether a difference exists in hospital readmission
      rates at 60 days postdischarge between patients who saw (intervention group) or
      did not see (control group) a pharmacist within 60 days of discharge and to
      describe the number and type of pharmacist interventions. DESIGN: Retrospective
      electronic record review. SETTING: Austin, TX, from January 2006 to January 2010.
      PATIENTS: 131 adult patients aged 18 to 65 years who were on at least three
      prescription medications. INTERVENTION: Pharmacist visit within 60 days post
      hospital discharge. MAIN OUTCOME MEASURE: Hospital readmission rates at 60 days
      postdischarge. RESULTS: The intervention and control groups did not differ
      regarding age or gender, but the control group had a higher percentage of whites,
      fewer medications, and fewer diseases. Chi-square analyses revealed that of 65
      patients in the control group, 28 (43.1%) were readmitted to the hospital within
      60 days of discharge compared with 12 of 66 (18.2%) intervention group patients
      (P = 0.0020). Pharmacists provided approximately two interventions per patient.
      The most frequently provided pharmacist interventions were medication counseling
      (88.1%) and drug dosage adjustment (52.2%). CONCLUSION: Patients on multiple
      prescription medications and with chronic diseases may benefit from a pharmacist
      visit within 60 days of hospital discharge. However, future studies are needed to
      further determine the effectiveness of pharmacists' interventions post-hospital
      discharge.

PMID- 22618977
TI  - Community pharmacist and technician communication with Spanish-speaking patients:
      needs assessment.
AB  - OBJECTIVES: To estimate the prevalence of community pharmacists and technicians
      who are capable of communicating with patients in Spanish and to estimate the
      need for Spanish language education initiatives for student pharmacists and
      pharmacists. DESIGN: U.S. census data (2006) were used to stratify states and
      counties based on Hispanic population densities. Protocols were used for
      telephone interviews with pharmacists in randomly selected national community
      pharmacies. RESULTS: Of 2,109 pharmacies contacted, 923 participated (43.8%) and
      165 (17.9%) reported having at least one full- or part-time Spanish-speaking
      pharmacist employed. Slightly more than one-third (n = 328; 35.6%) of pharmacies
      reported having one or more full-time Spanish-speaking technicians on staff. Of
      respondents, 70% indicated that they would be interested in attending a live
      (57.8%) or Web-based (62.9%) course to learn basic Spanish terms related to
      health care. When asked about the need for Spanish language education in pharmacy
      schools, 22.0% believed that a Spanish for health professionals course should be
      required, while 77.0% believed the course should be offered as an elective.
      CONCLUSION: Currently, a low proportion of community Spanish-speaking pharmacists
      and technicians are available to meet the needs of the Spanish-speaking limited
      English proficiency population in the United States. Pharmacy schools should
      offer resources to support Spanish language education initiatives. Community
      pharmacy administrators should provide resources to promote effective
      communication between pharmacists and their clientele.

PMID- 22618978
TI  - Impact of a pharmacist immunizer on adult immunization rates.
AB  - OBJECTIVES: To describe the immunization needs of indigent community-dwelling
      patients from a primary care center for the medically underserved, evaluate the
      impact of a pharmacist immunizer on vaccination rates of adults presenting for
      care, and evaluate the impact of a pharmacist immunizer on the percent of adult
      patients who are current on immunizations. METHODS: Prospective, controlled,
      parallel study among patients aged 18 to 79 years presenting for a medical
      appointment at a primary health care center located in a metropolitan area and
      providing care to the medically underserved. An immunization needs assessment
      (INA) was used to identify patients not current on adult immunizations. The
      intervention group received an offer to be immunized by a pharmacist using the
      results from the INA. Vaccination rates and percent of patients current on
      vaccinations were obtained using electronic medical records. RESULTS: Of 101
      participants, 82 (81.2%) needed at least one immunization. The availability of a
      pharmacist immunizer had a significant impact on the number of patients who were
      current on all immunizations at the completion of the study. The combination of
      the INA by a pharmacist demonstrated a significant effect on influenza and
      tetanus-diphtheria-acellular pertussis vaccination rates. The use of an identical
      tool by other health care providers did not have an impact on individual vaccine
      rates or the likelihood of patients being brought current on vaccinations.
      CONCLUSION: A dedicated pharmacist immunizer embedded in an indigent care primary
      health care clinic had a significant impact on increasing adult immunization
      rates and bringing patients current on vaccinations.

PMID- 22618979
TI  - OTC polyethylene glycol 3350 and pharmacists' role in managing constipation.
AB  - OBJECTIVES: To define constipation, assess the pharmacist's role in identifying
      and treating constipation, and review clinical evidence for the efficacy, safety,
      and tolerability of polyethylene glycol (PEG) 3350 (MiraLAX-Merck Consumer Care),
      an osmotic laxative now available over the counter (OTC), across a variety of
      patient populations routinely encountered in pharmacy settings. DATA SOURCES:
      Systematic PubMed search of the primary literature for constipation treatment
      guidelines and clinical trial results for PEG 3350. DATA SYNTHESIS: Pharmacists
      have a unique role in assisting patients with identifying and managing
      constipation. Multiple controlled clinical trials have established the efficacy,
      safety, and tolerability of PEG 3350 at its recommended dose of 17 g once daily.
      On the basis of this evidence, various professional groups have recommended PEG
      3350 for use in improving stool frequency and consistency in patients with
      constipation. PEG 3350 is approved for short-term use, including treatment of
      constipation caused by medications. CONCLUSION: Pharmacists can play an important
      role in managing constipation with OTC agents. Compared with other available OTC
      agents, PEG 3350 can be recommended to patients suffering from constipation on
      the basis of a large body of clinical evidence supporting its efficacy and
      safety, as well as the high patient acceptance shown for its palatability and
      once-daily dosing.

PMID- 22618980
TI  - Targeting cardiovascular medication adherence interventions.
AB  - OBJECTIVES: To determine whether adherence interventions should be administered
      to all medication takers or targeted to nonadherers. DATA SOURCES AND STUDY
      SELECTION: Systematic search (Medline and Embase, 1966-2009) of randomized
      controlled trials of interventions to improve adherence to medications for
      preventing or treating cardiovascular disease or diabetes. DATA EXTRACTION:
      Articles were classified as (1) broad interventions (targeted all medication
      takers), (2) focused interventions (targeted nonadherers), or (3) dynamic
      interventions (administered to all medication takers; real-time adherence
      information targets nonadherers as intervention proceeds). Cohen's d effect sizes
      were calculated. DATA SYNTHESIS: We identified 7,190 articles; 59 met inclusion
      criteria. Broad interventions were less likely (18%) to show medium or large
      effects compared with focused (25%) or dynamic (32%) interventions. Of the 33
      dynamic interventions, 6 used externally generated adherence data to target
      nonadherers. Those with externally generated data were less likely to have a
      medium or large effect (20% vs. 34.8% self-generated data). CONCLUSION: Adherence
      interventions targeting nonadherers are heterogeneous but may have advantages
      over broad interventions. Dynamic interventions show promise and require further
      study.

PMID- 22618981
TI  - School of pharmacy-based medication therapy management program: development and
      initial experience.
AB  - OBJECTIVE: To describe a school of pharmacy-community pharmacy collaborative
      model for medication therapy management (MTM) service and training. SETTING:
      University of Washington (UW) School of Pharmacy (Seattle), from July to December
      2008. PRACTICE DESCRIPTION: MTM services and training. PRACTICE INNOVATION: A
      campus-based MTM pharmacy was established for teaching, practice, and
      collaboration with community pharmacies to provide comprehensive medication
      reviews (CMRs) and MTM training. MAIN OUTCOME MEASURES: Number of collaborating
      pharmacies, number of patients contacted, number of CMRs conducted, and estimated
      cost avoidance (ECA). RESULTS: UW Pharmacy Cares was licensed as a Class A
      pharmacy (nondispensing) and signed "business associate" agreements with six
      community pharmacies. During July to December 2008, 10 faculty pharmacists
      completed training and 5 provided CMR services to 17 patients (5 telephonic and
      12 face-to-face interviews). A total of 67 claims (17 CMRs and 50 CMR-generated
      claims) were submitted for reimbursement of $1,642 ($96.58/CMR case). Total ECA
      was $54,250, averaging $3,191.19 per patient. Seven student pharmacists gained
      CMR interview training. CONCLUSION: Interest in collaboration by community
      pharmacies was lower than expected; however, the campus-community practice model
      addressed unmet patient care needs, reduced outstanding MTM CMR case loads,
      increased ECA, and facilitated faculty development and training of student
      pharmacists.

PMID- 22618982
TI  - A pharmacognostic and chemical study of ma huang (Ephedra vulgaris var.
      helvetica). 1925.

PMID- 22618983
TI  - Measles: a continuing saga.

PMID- 22618984
TI  - Ivacaftor, vismodegib, and ingenol mebutate.

PMID- 22618985
TI  - Science snippets. ABCs of diabetes care, targeted drug delivery with
      nanocarriers, and cost-effectiveness analysis methods of tomorrow.

PMID- 22618986
TI  - Aortic valve replacement for a patient with anomalous left coronary artery from
      the right sinus of Valsalva.
AB  - Anomalous origin of the left coronary artery (LCA) from the right sinus of
      Valsalva (RSOV) is an uncommon but clinically important feature. A 75-year-old
      man with progressive nocturnal dyspnea was diagnosed with severe aortic valve
      stenosis and moderate regurgitation. Preoperative computed tomographic scan
      revealed that the LCA originated from the RSOV separate from the right coronary
      artery and coursed into the ventricular septum. Because he did not experience any
      episodes of cardiac ischemia, isolated aortic valve replacement was performed
      using a 23-mm stented bioprosthesis without concomitant coronary
      revascularization. The postoperative course was free from coronary ischemia.

PMID- 22618987
TI  - Living-donor lobar lung transplantation for rapidly progressive interstitial
      pneumonia associated with clinically amyopathic dermatomyositis: report of a
      case.
AB  - Diffuse interstitial pneumonia (IP) associated with collagen disease is a rare
      indication for lung transplantation. The manifestations of collagen disease are
      variable and dermatomyositis (DM) is often considered a contraindication for lung
      transplantation because of active myositis and a high incidence of malignancy.
      Furthermore, clinically amyopathic dermatomyositis (C-ADM) is associated with
      rapidly progressive IP resulting in a poor prognosis. Bilateral living-donor
      lobar lung was transplanted in a 52-year-old female with rapidly progressive IP
      associated with C-ADM, and the postoperative course was uneventful. To our
      knowledge, this case represents the first living-donor lobar lung transplantation
      for a patient with rapidly progressive IP associated with C-ADM.

PMID- 22618988
TI  - Accessory lobe of the right liver mocking a pulmonary tumor in an adult woman.
AB  - We report a rare case of an accessory lobe of the liver in the right thoracic
      cavity with the past history of breast cancer. A 66-year-old woman underwent
      thoracotomy owing to a slowly growing suspected lung tumor identified by computed
      tomography. The intraoperative findings revealed an accessory lobe of the liver.
      If this possibility had been considered, the correct diagnosis could have been
      achieved using computed tomography with multi-directional scanning, so that an
      unnecessary operation could have been avoided.

PMID- 22618989
TI  - Rapidly progressive descending aortic pseudoaneurysm resulting from primary
      malignant fibrous histiocytoma.
AB  - A 66-year-old man with a history of asymptomatic bilateral swelling of the
      axillary lymph nodes was admitted with hoarseness and pain of the right knee.
      Computed tomography showed a large pseudoaneurysm deriving from descending aorta.
      We planned to resect the pseudoaneurysm, and repair the aortic wall. Resection of
      the pseudoaneurysm and patch-closure of the defect of the aorta were performed
      successfully. Pathological examination of the pseudoaneurysm revealed malignant
      fibrous histiocytoma. The clinical course was very miserable. Intrathoracic
      recurrence occurred 7 months after surgery, and he died of multiple brain
      metastases 10 months postoperatively.

PMID- 22618990
TI  - Successful surgical management of coronary perforation requiring pulmonary artery
      separation.
AB  - A 73-year-old woman with type III coronary perforation caused by failed
      angioplasty underwent emergency operation. It was impossible to stop the bleeding
      from the beating heart because the proximal Cx, which was the perforation site,
      was behind the main pulmonary artery. After establishing cardiopulmonary bypass,
      we separated the main pulmonary artery to secure hemostasis and performed
      coronary artery bypass grafting to the distal Cx. The postoperative course was
      uneventful therefore the patient was discharged on the tenth postoperative day.
      Surgical strategies are not standardized for coronary perforation and depend
      mainly on the surgical anatomy. In a situation like the present, which appears
      not to have been described previously, it is important to save the life of the
      patient by whatever means.

PMID- 22618991
TI  - Successful surgical removal of an entrapped intravascular ultrasonography
      catheter in the left circumflex coronary artery.
AB  - Entrapment of an intravascular ultrasonography (IVUS) catheter is an infrequent
      but serious complication associated with percutaneous coronary intervention
      (PCI). A 67-year-old man who presented with exertional chest pain had an
      angiographic finding of 99 % stenosis of left circumflex coronary artery. PCI
      with stent implantation was performed successfully with an assessment by IVUS
      showing adequate stent expansion and apposition. When the IVUS catheter was
      retracted, it became trapped at the stent strut. The stent was deformed and the
      IVUS catheter became stuck there. Ventricular fibrillation suddenly occurred with
      deterioration of the coronary flow. He was transferred to the operating room just
      after insertion of intra-aortic balloon pumping. The IVUS catheter, the
      guidewire, and the deformed stent were all removed under cardiopulmonary bypass.
      Coronary artery bypass graft with a saphenous vein was also performed at the more
      distal segment from the entrapment site. The postoperative course was uneventful
      with no graft occlusion.

PMID- 22618992
TI  - Coronary arterial compression caused by an aneurysm of the sinus of Valsalva with
      aortic prosthetic valve endocarditis.
AB  - Myocardial ischemia caused by coronary arterial compression by an aneurysm of the
      sinus of Valsalva is a particularly unusual complication. We describe a patient
      with aortic prosthetic valve endocarditis complicated with an aneurysm of the
      sinus of Valsalva. An 82-year-old woman was admitted to our hospital with a high
      fever and chest discomfort. She had undergone aortic valve replacement 3 years
      earlier. Computed tomography showed an aneurysm originating from the left and
      right aortic sinus that was compressing the proximal left anterior descending
      coronary artery. The aortic root was successfully replaced and antibiotic
      treatment was continued for 6 weeks after surgery.

PMID- 22618993
TI  - Posterior leaflet extension with a patch of bovine pericardium for type IIIb
      mitral regurgitation.
AB  - A 36-year-old man was referred to our hospital because of heart failure, and
      severe mitral regurgitation due to restriction of the posterior mitral leaflet
      was detected by an echocardiogram. We performed posterior leaflet extension with
      a patch of bovine pericardium. The postoperative course was uneventful, and the
      patient was discharged on postoperative day 23. Posterior leaflet extension is
      useful for mitral regurgitation due to posterior leaflet restriction.

PMID- 22618994
TI  - Intracerebral immune complex formation induces inflammation in the brain that
      depends on Fc receptor interaction.
AB  - In this study, we investigate the underlying mechanisms of antibody-mediated
      inflammation in the brain. We show that immune complexes formed in the brain
      parenchyma generate a robust and long-lasting inflammatory response,
      characterized by increased expression of the microglia markers CD11b, CD68 and
      FcRII/III, but no neutrophil recruitment. In addition to these histological
      changes, we observed transient behavioural changes that coincided with the
      inflammatory response in the brain. The inflammatory and behavioural changes were
      absent in Fc-gamma chain (Fcgamma)-deficient mice, while C1q-deficient mice were
      not different from wild-type mice. We conclude that, in the presence of antigen,
      antibodies can lead to a local immune complex-mediated inflammatory reaction in
      the brain parenchyma and indirectly induce neuronal tissue damage through
      recruitment and activation of microglia via Fcgamma receptors. These observations
      may have important implications for the development of therapeutic antibodies
      directed against neuronal antigens used for therapeutic intervention in
      neurological diseases.

PMID- 22618996
TI  - Species-specific differences in temporal and spatial variation in delta(13)C of
      plant carbon pools and dark-respired CO (2) under changing environmental
      conditions.
AB  - Stable carbon isotope signatures are often used as tracers for environmentally
      driven changes in photosynthetic delta(13)C discrimination. However, carbon
      isotope signatures downstream from carboxylation by Rubisco are altered within
      metabolic pathways, transport and respiratory processes, leading to differences
      in delta(13)C between carbon pools along the plant axis and in respired CO(2).
      Little is known about the within-plant variation in delta(13)C under different
      environmental conditions or between species. We analyzed spatial, diurnal, and
      environmental variations in delta(13)C of water soluble organic matter
      (delta(13)C(WSOM)) of leaves, phloem and roots, as well as dark-respired
      delta(13)CO(2) (delta(13)C(res)) in leaves and roots. We selected distinct light
      environments (forest understory and an open area), seasons (Mediterranean spring
      and summer drought) and three functionally distinct understory species (two
      native shrubs-Halimium halimifolium and Rosmarinus officinalis-and a woody
      invader-Acacia longifolia). Spatial patterns in delta(13)C(WSOM) along the plant
      vertical axis and between respired delta(13)CO(2) and its putative substrate were
      clearly species specific and the most delta(13)C-enriched and depleted values
      were found in delta(13)C of leaf dark-respired CO(2) and phloem sugars, ~-15 and
      ~-33 0/00, respectively. Comparisons between study sites and seasons revealed
      that spatial and diurnal patterns were influenced by environmental conditions.
      Within a species, phloem delta(13)C(WSOM) and delta(13)C(res) varied by up to 4
      0/00 between seasons and sites. Thus, careful characterization of the magnitude
      and environmental dependence of apparent post-carboxylation fractionation is
      needed when using delta(13)C signatures to trace changes in photosynthetic
      discrimination.

PMID- 22618997
TI  - The context of available options affects health care decisions: a generalization
      study.
AB  - BACKGROUND: When a given option is presented along with 2 alternatives, similar
      to each other, health care professionals choose it more often than when it is
      presented with just one of the alternatives. This inconsistent decision pattern
      may depend on the conflict generated from choosing between 2 highly similar
      options. OBJECTIVE: To generalize the effect by using realistic scenarios that
      involve 2 alternatives displaying various degrees of similarity. METHODS: One
      hundred fifty-five psychiatrists, 149 gynecologists, and 89 nurse managers had to
      indicate the treatment they would recommend in clinical scenarios containing
      either 3 options or just 2 of them. The similarity between the 2 alternatives
      varied across scenarios, ranging from a very high (psychiatric scenario) to an
      only moderately high (nursing management scenario) to a limited level
      (gynecological scenario). RESULTS: Professionals chose the focal option more
      often when both alternatives were available. The paradoxical effect occurred for
      all scenarios--namely, when the alternatives were medication variants
      (psychiatric scenario), when most of the features they shared produced their
      effect at a different extent in the 2 cases (nursing management scenario), and
      some of their consequences were at variance (gynecological problem). CONCLUSIONS:
      The context of available options affects professionals' choices when the
      alternatives are similar but also when they present diverging features.
      Professionals need to be aware of such a source of practice variability and are
      encouraged to consider each option per se before they compare the available
      options.

PMID- 22618995
TI  - The genetics and neuropathology of Alzheimer's disease.
AB  - Here we review the genetic causes and risks for Alzheimer's disease (AD). Early
      work identified mutations in three genes that cause AD: APP, PSEN1 and PSEN2.
      Although mutations in these genes are rare causes of AD, their discovery had a
      major impact on our understanding of molecular mechanisms of AD. Early work also
      revealed the epsilon4 allele of the APOE as a strong risk factor for AD.
      Subsequently, SORL1 also was identified as an AD risk gene. More recently,
      advances in our knowledge of the human genome, made possible by technological
      advances and methods to analyze genomic data, permit systematic identification of
      genes that contribute to AD risk. This work, so far accomplished through single
      nucleotide polymorphism arrays, has revealed nine new genes implicated in AD risk
      (ABCA7, BIN1, CD33, CD2AP, CLU, CR1, EPHA1, MS4A4E/MS4A6A, and PICALM). We review
      the relationship between these mutations and genetic variants and the
      neuropathologic features of AD and related disorders. Together, these discoveries
      point toward a new era in neurodegenerative disease research that impacts not
      only AD but also related illnesses that produce cognitive and behavioral
      deficits.

PMID- 22618998
TI  - How well do commonly used data presentation formats support comparative
      effectiveness evaluations?
AB  - BACKGROUND: Good decisions depend on an accurate understanding of the comparative
      effectiveness of decision alternatives. The best way to convey data needed to
      support these comparisons is unknown. OBJECTIVE: To determine how well 5 commonly
      used data presentation formats convey comparative effectiveness information.
      METHODS: The study was an Internet survey using a factorial design. Participants
      consisted of 279 members of an online survey panel. Study participants compared
      outcomes associated with 3 hypothetical screening test options relative to 5
      possible outcomes with probabilities ranging from 2 per 5000 (0.04%) to 500 per
      1000 (50%). Data presentation formats included a table, a "magnified" bar chart,
      a risk scale, a frequency diagram, and an icon array. Outcomes included the
      number of correct ordinal judgments regarding the more likely of 2 outcomes, the
      ratio of perceived versus actual relative likelihoods of the paired outcomes, the
      intersubject consistency of responses, and perceived clarity. RESULTS: The mean
      number of correct ordinal judgments was 12 of 15 (80%), with no differences among
      data formats. On average, there was a 3.3-fold difference between perceived and
      actual likelihood ratios (95% confidence interval = 3.0-3.6). Comparative
      judgments based on flowcharts, icon arrays, and tables were all significantly
      more accurate and consistent than those based on risk scales and bar charts (P <
      0.001). The most clearly perceived formats were the table and the flowchart. Low
      subjective numeracy was associated with less accurate and more variable data
      interpretations and lower perceived clarity for icon displays, bar charts, and
      flow diagrams. CONCLUSIONS: None of the data presentation formats studied can
      reliably provide patients, especially those with low subjective numeracy, with an
      accurate understanding of comparative effectiveness information.

PMID- 22618999
TI  - Axillary vein thrombosis as the first clinical manifestation of inflammatory
      breast cancer: report of a case.
AB  - Inflammatory breast cancer is a rare and aggressive form of breast cancer. Venous
      thromboembolism is often related to cancer conditions but this report presents a
      case in which the thromboembolic event predicted the diagnosis of cancer. A 48
      year-old female was admitted with the evidence of acute right axillary vein
      thrombosis. There was also erythema and edema of the skin of the right breast.
      Further evidence revealed a case of inflammatory breast cancer. The patient
      underwent anticoagulant therapy, and neoadjuvant systemic chemotherapy was
      initiated. The patient underwent extensive unilateral mastectomy following
      neoadjuvant chemotherapy. Follow-up (after 2 months of anticoagulation therapy
      for deep vein thrombosis) revealed recanalization of the right axillary vein,
      without evidence of residual thrombus. A case of acute vein thrombosis as the
      first manifestation of breast cancer may delay the diagnosis and subsequent
      appropriate treatment.

PMID- 22619000
TI  - Postoperative atrial fibrillation: mechanism, prevention, and future perspective.
AB  - Postoperative atrial fibrillation (POAF) is the most common complication after
      cardiac surgery, despite improvements in anesthesia, surgical techniques, and
      medical therapies. Although beta-blockers have been proven to be effective, the
      incidence of POAF is around 20 % even with these agents. The mechanism of POAF is
      not fully elucidated and no optimal strategy has been established for POAF. There
      are two important elements of "structural" and "electrical" remodelling of the
      atrium in the mechanism of POAF. A patient's age and preoperative left atrial
      fibrosis can predict POAF associated with structural remodelling. Although
      inflammation and oxidative stress during cardiac surgery may be the underlying
      mechanisms for electrical remodelling causing POAF, there are no reliable
      clinical parameters for their detection. Nonetheless, postoperative P-wave
      dispersion and electromechanical delay, which reflects excitation-contraction
      coupling abnormalities, could be new parameters for POAF. In conclusion, despite
      the importance of prevention of POAF, there are only a few parameters for
      predicting POAF. It is therefore necessary to consider both disease-mediated
      structural remodeling before surgery and electrical remodeling caused by cardiac
      surgery.

PMID- 22619001
TI  - Adrenal cavernous hemangioma with subclinical Cushing's syndrome: report of a
      case.
AB  - Cavernous hemangioma of the adrenal gland is a rare tumor, which does not usually
      have endocrinological function. We report to our knowledge, the third documented
      case of a functioning adrenal hemangioma. Interestingly, this tumor indicated
      glucocorticoid hypersecretion, whereas the two previous cases showed
      mineralocorticoid hypersecretion. The tumor was 5 cm in diameter with typical
      computed tomography and magnetic resonance imaging findings. Subclinical
      Cushing's syndrome was diagnosed preoperatively, as there was insufficient
      suppression of cortisol by low-dose dexamethasone, a low adrenocorticotropic
      hormone (ACTH) concentration, and diminished ACTH and cortisol circadian rhythms
      without the typical clinical manifestation and symptoms of hypercortisolism.
      Intraoperative hypotension occurred immediately after tumor removal and following
      postoperative adrenal insufficiency, which support that the tumor was
      hyperfunctioning. The postoperative adrenal insufficiency had recovered
      completely by 12 months after the operation.

PMID- 22619002
TI  - Conformations of helical Aib peptides containing a pair of L-amino acid and D
      amino acid.
AB  - A pair of L-leucine (L-Leu) and D-leucine (D-Leu) was incorporated into a
      aminoisobutyric acid (Aib) peptide segments. Thedominant conformations of four
      hexapeptides, Boc-L-Leu-Aib-Aib-Aib-Aib-L-Leu-OMe (1a), Boc-D-Leu-Aib-Aib-Aib-Aib
      L-Leu-OMe(1b), Boc-Aib-Aib-L-Leu-L-Leu-Aib-Aib-OMe (2a), and Boc-Aib-Aib-D-Leu-L
      Leu-Aib-Aib-OMe (2b), were investigated by IR,1H NMR, CD spectra, and X-ray
      crystallographic analysis. All peptides 1a,b and 2a,b formed 310-helical
      structures in solution. X-ray crystallographic analysis revealed that right
      handed (P) 310-helices were present in 1a and 1b and a mixture of right-handed(P)
      and left-handed (M) 310-helices was present in 2b in their crystalline states.

PMID- 22619003
TI  - Measuring true Young's modulus of a cantilevered nanowire: effect of clamping on
      resonance frequency.
AB  - The effect of clamping on resonance frequency and thus measured Young's modulus
      of nanowires (NWs) is systematically investigated via a combined experimental and
      simulation approach. ZnO NWs are used in this work as an example. The resonance
      tests are performed in situ inside a scanning electron microscope and the NWs are
      cantilevered on a tungsten probe by electron-beam-induced deposition (EBID) of
      hydrocarbon. EBID is repeated several times to deposit more hydrocarbons at the
      same location. The resonance frequency increases with the increasing clamp size
      until approaching that under the "fixed" boundary condition. The critical clamp
      size is identified as a function of NW diameter and NW Young's modulus. This
      work: 1) exemplifies the importance of considering the effect of clamping in
      measurements of Young's modulus using the resonance method, and 2) demonstrates
      that the true Young's modulus can be measured if the critical clamp size is
      reached. Design guidelines on the critical clamp size are provided. Such design
      guidelines can be extended to other one-dimensional nanostructures such as carbon
      nanotubes.

PMID- 22619004
TI  - Improved outcome in pediatric AML due to augmented supportive care.
AB  - We conducted a retrospective review of patients treated following the MRC acute
      myeloid leukemia (AML) 10 protocol to determine if supportive care measures
      sequentially introduced by our institution led to a significant improvement in
      treatment-related mortality (TRM) in newly diagnosed pediatric patients with AML.
      Patients were partitioned based on supportive care measures into era1, from 1996
      to 2002 (n = 20), and era2, from 2003 to 2011 (n = 40). The introduced supportive
      care measures reduced the TRM from 23.4% in era1 to 2.5% in era2 (P = 0.034). The
      results demonstrate that supportive care is a significant factor in determining
      the outcome of childhood AML.

PMID- 22619005
TI  - Early recurrence or submucosal residual of laryngeal squamous cell carcinoma:
      diagnosis by CT-guided endolaryngeal core biopsy on a transcutaneous approach.
AB  - BACKGROUND: Ultrasound and CT-guided biopsy is a common procedure for histologic
      diagnosis of recurrence of head and neck squamous cell carcinoma. The present
      study describes a novel CT-guided endolaryngeal puncture site. METHODS AND
      RESULTS: A 59-year-old man was treated for a T2N0M0 supraglottic laryngeal tumor
      by laser resection and bilateral lymph node dissection; exeresis was judged
      complete. Six-month follow-up found persistent dysphonia. Endoscopic examination
      and iterative biopsy gave reassuring results, but (18) fluorodeoxyglucose
      positron emission tomography-CT ((18) FDG PET-CT) found highly suspicious
      increased right hemilaryngeal metabolic activity. Diagnosis of residual tumor was
      confirmed on CT-guided endolaryngeal biopsy. CONCLUSIONS: Image-guided biopsy is
      the technique of choice in head and neck lesions that are deep or difficult to
      palpate and inaccessible to endoscopy. It is especially useful when recurrence is
      suspected after radiation therapy or cancer surgery. Many puncture sites have
      been reported in the literature; the present novel laryngeal approach extends the
      range of image-guided biopsy, although further studies will be needed to assess
      possible morbidity.

PMID- 22619007
TI  - Silibinin triggers apoptosis and cell-cycle arrest of SGC7901 cells.
AB  - Silibinin, a flavonoid compound, has shown to be of chemopreventive potential
      against many cancers. However, its efficacy against gastric cancer has not been
      well elucidated. Here, we assessed the activity of Silibinin on apoptosis and
      cell-cycle arrest in human gastric cells culture system using SGC-7901 as the
      model. Silibinin treatment could inhibit the cell growth and cause a prominent G2
      phase arrest and apoptosis in dose- and time-dependent manner. In mechanistic
      studies, Silibinin decreased the protein level of p34cdc2, which might be the
      possible molecular mechanism of Silibinin efficacy on the growth inhibition in
      SGC-7901 cells. In addition, Silibinin caused an increase in p53 and p21 protein
      level as well as mRNA levels. Interestingly, Silibinin-induced apoptosis in SGC
      7901 cells was independent of caspases activation. These results indicated that
      Silibinin is a cell-cycle regulator and apoptosis inducer in human gastric
      carcinoma SGC-7901 cells and might be used as a candidate chemopreventive agent
      for gastric carcinoma prevention and intervention.

PMID- 22619008
TI  - [Interdisciplinary cooperation: prerequisite in clarification of pathogenesis as
      well as diagnostic and therapeutic strategies].

PMID- 22619009
TI  - [Abdominal aortic aneurysm].

PMID- 22619010
TI  - [Metabolic diseases and periodontitis].

PMID- 22619011
TI  - [Nutrition in patients with dementia - a challenge to all].

PMID- 22619012
TI  - [Chronic lymphocytic leukemia].

PMID- 22619013
TI  - [Intensive care management of acute pancreatitis].

PMID- 22619014
TI  - [HDL/LDL - how high, how low?].

PMID- 22619015
TI  - [Chronic obstructive pulmonary disease (COPD)].

PMID- 22619016
TI  - [Vasculitis].

PMID- 22619017
TI  - [Screening colonoscopy].

PMID- 22619018
TI  - [44-year-old man with alcohol- and nicotinabusus and acut skin lesions].

PMID- 22619019
TI  - [Lymphoma-induced antiphospholipid syndrome  as a cause of splenic infarction].
AB  - HISTORY AND ADMISSION FINDINGS: A 71-year-old man presented with bilateral
      sialadenosis of the parotid gland, episodes of fever up to 39  degrees C, general
      malaise and weight loss of 5 kg within the last 6 weeks. At physical examination
      peripheral lymph nodes were not palpable. INVESTIGATIONS: Laboratory studies
      revealed a normal white blood cell count, anemia and thrombocytopenia. Serum C
      reactive protein and lactate dehydrogenase were elevated on admission and rose
      further. Plasmatic coagulation was characterized by prolonged partial
      thromboplastin time and reduced prothrombin time. Abdominal computed tomography
      showed an enlarged spleen with irregular hypodense areas, indicating splenic
      infarctions. Enlarged lymph nodes were noted at the paraaortic region and in the
      splenic hilum. DIAGNOSIS: As the patient's condition deteriorated from day to day
      a diagnosis had to be enforced. Splenectomy was thus performed which confirmed
      the CT findings of numerous infarcted areas. A marginal zone lymphoma was found
      within the splenic hilar lymph nodes. High titer serum antibodies against
      cardiolipin confirmed the diagnosis of secondary antiphospholipid syndrome (APS).
      TREATMENT AND COURSE: Oral anticoagulation with phenprocoumone was started; in
      addition, chemotherapy with rituximab, cyclophosphamide, vincristin and
      prednisolone (R-CHOP) was initiated. Despite clinical recovery serological
      markers of APS remained elevated. The lymphoma recurred only six months after
      chemotherapy had been completed, and the patient died two months later.
      CONCLUSION: Because of its potentially fatal consequences anticoagulation and
      treatment of the underlying disease are crucial in secondary APS.

PMID- 22619020
TI  - [Development of pharmaceutical expenses  in German private health insurance].
AB  - Health Insurance costs in Germany have grown by 3 % p. a. over the last ten years
      and amount to approx. 280 bn EUR in 2009. While costs for stationary treatment as
      the largest cost category have been intensely analyzed over the past years,
      pharmaceutical expenses have been analyzed in less detail, mostly focusing on the
      Statutory Health Insurance side, even though pharmaceutical expenses have grown
      almost twice as much as costs for ambulant treatments. This research article
      therefore focuses on the question how pharmaceutical expenses in a large German
      private health insurance company are allocated with respect to age and indication
      groups, and how those have developed during the past four years. Therefore, the
      data of a private health insurance company with more than 600.000 customers was
      split into price and volume effects per age group to understand if price or
      volume drives the cost development. Additionally, the two largest indication
      groups are analyzed in detail. As a result, both price and volume effects drive
      an overall cost increase of 7,3 %. These effects are even stronger in older age
      groups. This strong cost increase is not sustainable for the German health
      insurance system over a longer period of time and will even further increase due
      to the ageing of the German population.

PMID- 22619021
TI  - Promise and challenges of human iPSC-based hematologic disease modeling and
      treatment.
AB  - Postnatal hematopoietic stem cells (HSCs) from umbilical cord blood and adult
      marrow/blood have been successfully used for treating various human diseases in
      the past several decades. However, the availability of optimal numbers of HSCs
      from autologous patients or allogeneic donors with adequate match remains a great
      barrier to improve and extend HSC and marrow transplantation to more needing
      patients. In addition, the inability to expand functional human HSCs to
      sufficient quantity in the laboratory has hindered our research and understanding
      of human HSCs and hematopoiesis. Recent development in reprogramming technology
      has provided patient-specific pluripotent stem cells (iPSCs) as a powerful
      enabling tool for modeling disease and developing therapeutics. Studies have
      demonstrated the potential of human iPSCs, which can be expanded exponentially
      and amenable for genome engineering, for using in modeling both inherited and
      acquired blood diseases. Proof-of-principle studies have also shown the
      feasibility of iPSCs in gene and cell therapy. Here, we review the recent
      development in iPSC-based blood disease modeling, and discuss the unsolved issues
      and challenges in this new and promising field.

PMID- 22619023
TI  - Prognostic factors and long-term outcome following surgical treatment of 76
      patients with spontaneous cerebellar haematoma.
AB  - BACKGROUND: Although large spontaneous cerebellar haematomas are associated with
      high mortality, surgical treatment may be life-saving. We evaluated the clinical
      outcome and identified prognostic factors in 76 patients with cerebellar
      haematoma, all treated with suboccipital decompression, haematoma evacuation and
      external ventricular drainage. METHODS: Patients receiving surgical and
      neurocritical care treatment within a 10-year period were included. Level of
      consciousness during hospitalisation was evaluated using the Glasgow Coma Scale
      (GCS) score. Outcome was assessed with the modified Rankin Scale (mRS).
      Predictive prognostic factors were analysed using univariate and multivariate
      regression analysis. RESULTS: Prior to surgery, the median GCS score was 8.6
      (range 3-13). At discharge it had improved to 12.1 (4-15) (p < 0.05). The median
      long-term follow-up period was 70.5 (22-124) months. At 6 months post-surgery, 19
      patients were dead and 28 patients had a good outcome (mRS < 3). In the long term
      (70.5 months), 31 patients (41.9 %) were dead and the outcome was good in 27
      patients (37.8 %). Although approximately 25 % of patients >65 years old had a
      favourable outcome, age was the strongest negative predictor for a bad outcome at
      6 months and long term (p = 0.02 and p = 0.01, respectively). The level of
      consciousness before surgery did not influence the 6-month or long-term outcome
      (p = 0.39 and p = 0.65, respectively). CONCLUSIONS: Although mortality was high,
      significant complications from the treatment were rare and most survivors had a
      good outcome, reaching functional independence. High age was the strongest
      prognostic factor for an unfavourable outcome.

PMID- 22619024
TI  - Clinical features of silent corticotroph adenomas.
AB  - BACKGROUND: Silent corticotrph adenomas represent a distinct pathological subtype
      of non-functioning pituitary adenomas that are traditionally believed to carry a
      more aggressive biological behavior and higher potential for recurrence. METHODS:
      We conducted a retrospective review of all silent corticotroph adenomas treated
      and followed at our institution over the last 10 years. We reviewed clinical,
      radiological and pathological features. The series was compared to a matched
      cohort of ACTH-negative, non-functioning adenomas to compare clinical,
      radiological and pathological features. Our results were compared to the
      literature. RESULTS: Twenty patients met our inclusion criteria. Fifty-six
      percent of the patients were females. Mean age was 51 years (range 24-78 years).
      Visual dysfunction was the most common clinical presentation (38 %). Thirteen
      percent of the cases presented with acromegaly secondary to double adenoma
      (silent corticotroph adenoma and growth hormone adenoma) and 13 % presented with
      pituitary tumor apoplexy. All the tumors were macroadenomas. Frank cavernous
      sinus invasion occurred in 31 % of the cases. The patients who presented with
      acromegaly did not achieve remission postoperatively. In the remaining patients,
      recurrence occurred in 14 % of the cases over a mean follow-up period of 41
      months. Compared to non-functioning adenomas, silent corticotroph adenomas were
      more likely to bleed (p value 0.014) and have double adenoma (p value 0.047).
      There was no difference in recurrence rates between silent corticotroph adenomas
      and non-functioning adenomas (p value 0.647). CONCLUSION: These results suggest
      that silent corticotroph adenomas have some unique features compared to non
      functioning adenomas. Within the limits of our follow-up duration and sample size
      and our review of the literature, we would recommend that the traditional view to
      manage all silent corticotroph adenomas with adjuvant radiation should be
      reconsidered. We suggest adopting an initially more conservative follow-up
      surveillance and delay of upfront radiation until there is clear evidence of
      tumor recurrence.

PMID- 22619025
TI  - Systematic review of haemorrhage and rupture of hepatocellular adenomas.
AB  - BACKGROUND: Although benign in itself, hepatocellular adenoma (HCA) can be
      complicated by hormone-induced growth, and subsequent haemorrhage and rupture.
      The exact risk of haemorrhage and rupture is not known. This systematic review of
      the literature was carried out with the aim of estimating the risk of haemorrhage
      and rupture in HCA. METHODS: A systematic literature search of the PubMed and
      Embase databases was performed for all articles relevant to haemorrhage and/or
      rupture of HCA, published between 1969 and March 2011. RESULTS: Twenty-eight
      articles met the selection criteria, containing a total of 1176 patients.
      Haemorrhage was reported with an overall frequency of 27.2 per cent among
      patients, and in 15.8 per cent of all HCA lesions. Rupture and intraperitoneal
      bleeding were reported in 17.5 per cent of patients. Bleeding was the first
      symptom in 68.5 per cent of patients with a bleeding HCA. Six of 13 articles
      reporting the size of HCA lesions in which bleeding occurred mentioned
      haemorrhage in HCAs smaller than 5 cm. CONCLUSION: Haemorrhage and rupture are
      common in patients with HCA.

PMID- 22619026
TI  - Management of hypertriglyceridemia in children with acute lymphoblastic leukemia
      under persistent therapy with glucocorticoids and L-asparaginase during induction
      chemotherapy.

PMID- 22619027
TI  - Efficacy of low-dose hCG in late follicular phase in controlled ovarian
      stimulation using GnRH agonist protocol.
AB  - OBJECTIVE: Safe, simple and cost-effective protocol is an important goal in ART
      cycles. The aim of this prospective study was whether administration of low-dose
      hCG in late follicular phase can be used clinically to replace gonadotropin
      administration in GnRH long protocol. MATERIALS AND METHODS: 122 patients who
      were candidates for ART enrolled the study and randomly divided into two groups.
      The control group (n = 62) received standard long protocol and gonadotropin
      administration continued until the day of hCG injection (10,000 IU) for final
      follicular maturation. The study group (n = 60) received GnRH long protocol and
      when at least >=6 follicles with mean diameter >=12 mm were observed in both
      ovaries, hMG was displaced by 200 IU per day of hCG until final follicular
      maturation. RESULTS: There were no significant differences in age, basal FSH,
      infertility duration and infertility etiology between two groups. There were no
      statistically significant differences between two groups regarding chemical
      pregnancy, clinical pregnancy, ongoing pregnancy, and abortion per cycle (50, 40,
      40, and 20 % in study group vs. 45.2, 35.5, 35.5, and 21.4 % in control group,
      respectively). Mean dose of used gonadotropins was significantly higher in
      control group than that in the study group (2,524 +/- 893 IU in control group and
      1,439 +/- 433 IU in study group) (p = 0.000). CONCLUSION: According to our data,
      we recommend the use of low-dose hCG in GnRH long protocol because of lower doses
      of used gonadotropins.

PMID- 22619028
TI  - Deterioration of myocardial tissue Doppler indices in a case of fetal hydrothorax
      as a promising indication for clinical intervention before the development of
      nonimmune hydrops fetalis.

PMID- 22619029
TI  - Genetic study of FGF19 receptor variants in gallstone disease.

PMID- 22619030
TI  - Thermal tolerance of the crab Pachygrapsus marmoratus: intraspecific differences
      at a physiological (CTMax) and molecular level (Hsp70).
AB  - Temperature is one of the most important variables influencing organisms,
      especially in the intertidal zone. This work aimed to test physiological and
      molecular intraspecific differences in thermal tolerance of the crab Pachygrapsus
      marmoratus (Fabricius, 1787). The comparisons made focused on sex, size, and
      habitat (estuary and coast) differences. The physiological parameter was upper
      thermal limit, tested via the critical thermal maximum (CTMax) and the molecular
      parameter was total heat shock protein 70 (Hsp70 and Hsp70 plus Hsc70)
      production, quantified via an enzyme-linked imunosorbent assay. Results showed
      that CTMax values and Hsp70 production are higher in females probably due to
      different microhabitat use and potentially due to different hormonal regulation
      in males and females. Among females, non-reproducing ones showed a higher CTMax
      value, but no differences were found in Hsp70, even though reproducing females
      showed higher variability in Hsp70 amounts. As reproduction takes up a lot of
      energy, its allocation for other activities, including stress responses, is
      lower. Juveniles also showed higher CTMax and Hsp70 expression because they occur
      in greater shore heights and ageing leads to alterations in protein synthesis.
      Comparing estuarine and coastal crabs, no differences were found in CTMax but
      coastal crabs produce more Hsp70 than estuarine crabs because they occur in drier
      and hotter areas than estuarine ones, which occur in moister environments. This
      work shows the importance of addressing intraspecific differences in the stress
      response at different organizational levels. This study shows that these
      differences are key factors in stress research, climate research, and
      environmental monitoring.

PMID- 22619031
TI  - Optoelectronic properties of dicyanofluorene-based n-type polymers.
AB  - Three new donor-acceptor-type copolymers (P1-P3) consisting of dicyanofluorene as
      acceptor and various donor moieties were designed and synthesized. Optoelectronic
      properties were studied in detail by means of UV-visible absorption and
      fluorescence spectroscopy, cyclic voltammetry, space-charge-limited current
      (SCLC), flash-photolysis time-resolved microwave conductivity (FP-TRMC), and
      density functional theory (DFT). All polymers showed strong absorption in the UV
      visible region and the absorption maximum undergoes redshift with an increasing
      number of thiophene units in the polymer backbone. SCLC analysis showed that the
      electron mobilities of the polymers in the bulk state were 1 to 2 orders higher
      than that of the corresponding hole mobilities, which indicated the n-type nature
      of the materials. By using FP-TRMC, the intrapolymer charge-carrier mobility was
      assessed and compared with the interpolymer mobility obtained by SCLC. The
      polymers exhibited good electron-accepting properties sufficiently high enough to
      oxidize the excited states of regioregular poly(3-hexylthiophene) (P3HT (donor)),
      as evident from the FP-TRMC analysis. The P3 polymer exhibited the highest FP
      TRMC transients in the pristine form as well as when blended with P3HT. Use of
      these polymers as n-type materials in all-polymer organic solar cells was also
      explored in combination with P3HT. In accordance with the TRMC results, P3
      exhibited superior electron-transport and photovoltaic properties to the other
      two polymers, which is explained by the distribution of the energy levels of the
      polymers by using DFT calculations.

PMID- 22619033
TI  - Relationship between potential aggregation-prone regions and HLA-DR-binding T
      cell immune epitopes: implications for rational design of novel and follow-on
      therapeutic antibodies.
AB  - Aggregation and unwanted immunogenicity are hurdles to avoid in successful
      commercial development of antibody-based therapeutics. In this article, the
      relationship between aggregation-prone regions (APRs), capable of forming cross
      beta motifs/amyloid fibrils, and major histocompatibility complex class II
      restricted human leukocyte antigen (HLA)-DR-binding T-cell immune epitopes
      (TcIEs) is analyzed using amino acid sequences of 25 therapeutic antibodies, 55
      TcIEs recognized by T-regulatory cells (tregitopes), 1000 randomly generated 15
      residue-long peptides, 2257 human self-TcIEs (autoantigens), and 11 peptides in
      HLA-peptide cocrystal structures. Sequence analyses from these diverse sources
      consistently show a high level of correlation between APRs and TcIEs:
      approximately one-third of TcIEs contain APRs, but the majority of APRs occur
      within TcIE regions (TcIERs). Tregitopes also contain APRs. Most APR-containing
      TcIERs can bind multiple HLA-DR alleles, suggesting that aggregation-driven
      adverse immune responses could impact a broad segment of patient population. This
      article has identified common molecular sequence-structure loci that potentially
      contribute toward both manufacturability and safety profiles of the therapeutic
      antibodies, thereby laying a foundation for simultaneous optimization of these
      attributes in novel and follow-on candidates. Incidence of APRs within TcIERs is
      not special to biotherapeutics, self-TcIEs from human proteins, involved in
      various diseases, also contain predicted APRs and experimentally proven amyloid
      fibril-forming peptide sequence portions.

PMID- 22619032
TI  - Lineage targeted MHC-II transgenic mice demonstrate the role of dendritic cells
      in bacterial-driven colitis.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) pathogenesis involves an
      inadequately controlled immune reaction to intestinal microbiota, and CD4(+) T
      cells, dependent on MHC class II (MHC-II) processing and presentation by antigen
      presenting cells (APC), play important roles. The role of professional APC
      (macrophages and dendritic cells [DCs]) and nonprofessional APC (intestinal
      epithelial cells [IECs]) in microbial-driven intestinal inflammation remains
      controversial. METHODS: We generated transgenic animals on an MHC-II(-/-) genetic
      background in which MHC-II is expressed on 1) DC via the CD11c promoter (CD11cTg)
      or 2) IEC via the fatty acid binding protein (liver) promoter (EpithTg). These
      mice were crossed with Rag2(-/-) mice to eliminate T and B cells (CD11cTg/Rag2(-/
      ) and EpithTg/Rag2(-/-)). Helicobacter bilis (Hb) infection and adoptive transfer
      (AT) of naive CD4 T cells were used to trigger IBD. RESULTS: CD11cTg/Rag2(-/-)
      mice infected with Hb+AT developed severe colitis within 3 weeks post-AT, similar
      to disease in positive control Rag2(-/-) mice infected with Hb+AT. CD11cTg/Rag2(
      /-) mice given AT alone or Hb alone had significantly less severe colitis. In
      contrast, EpithTg/Rag2(-/-) mice infected with Hb+AT developed mild colitis by 3
      weeks and even after 16 weeks post-AT had only mild lesions. CONCLUSIONS: MHC-II
      expression restricted to DCs is sufficient to induce severe colitis in the
      presence of T cells and a microorganism such as Hb within 3 weeks of AT.
      Expression of MHC-II solely on IEC in the presence of a microbial trigger and T
      cells was insufficient to trigger severe colitis.

PMID- 22619035
TI  - Successful en bloc resection of an esophageal hemangioma by     endoscopic
      submucosal dissection.

PMID- 22619034
TI  - Hematuria after endoscopic ultrasound-guided fine needle aspiration     of a
      renal tumor in von Hippel-Lindau disease.

PMID- 22619036
TI  - Double common bile duct visualized by SpyGlass cholangioscopy.

PMID- 22619037
TI  - A rare cause of gastric outlet obstruction: gastritis cystica     profunda
      accompanied by adenocarcinoma.

PMID- 22619038
TI  - Varicella zoster-associated gastric ulcers, hepatitis and     pancreatitis in an
      immunocompromised patient.

PMID- 22619039
TI  - Primary signet-ring cell carcinoma of the pancreas diagnosed by     endoscopic
      retrograde pancreatic duct biopsy: a case report with an     immunohistochemical
      study.

PMID- 22619040
TI  - Quantification of the effect of treatment duration on local-regional failure
      after definitive concurrent chemotherapy and intensity-modulated radiation
      therapy for squamous cell carcinoma of the head and neck.
AB  - BACKGROUND: The purpose of this study was to quantify the effect of treatment
      duration on locoregional progression after definitive concurrent chemoradiation
      (CCRT) for squamous cell carcinoma of the head and neck (SCCHN). METHODS: We
      conducted a retrospective chart review of patients treated between 2004 and 2010.
      After a prior analysis, measures were taken to limit therapy beyond 7 weeks.
      Comparison of outcomes were made between cohorts 1 (2004-2007, n = 78) and 2
      (2007-2010, n = 62). RESULTS: Median therapy duration was statistically
      significantly different between cohorts as follows: 51 days, cohort 1 and 46
      days, cohort 2 (p < .01). Locoregional progression in cohorts 1 and 2 was 19% and
      5% (p = .01), respectively. On multivariate analysis, patients with prolonged
      treatment (>=57 days) had an 8-fold increase in risk of locoregional progression
      compared to patients who completed on time (p < .01). CONCLUSION: Treatment
      duration was a significant predictor of locoregional progression in patients with
      SCCHN who received definitive CCRT.

PMID- 22619041
TI  - Mechanistic determinants of biotherapeutics absorption following SC
      administration.
AB  - The subcutaneous (SC) route is of growing interest for the administration of
      biotherapeutics. Key products on the biotherapeutic market such as insulins, but
      also several immunoglobulins or Fc-fusion proteins, are administered SC. Despite
      the importance of the SC route, the available knowledge about the processes
      involved in the SC absorption of biotherapeutics is limited. This review
      summarizes available information on the physiology of the SC tissue and on the
      pharmacokinetic processes after SC administration including "first pass
      catabolism" at the administration site as well as transport in the extracellular
      matrix of the SC tissue, followed by absorption into the blood circulation or the
      lymphatic system. Both monoclonal antibodies and other biotherapeutics are
      discussed. Determinants of absorption after SC administration are summarized
      including compound properties such as charge or molecular weight. Scale-up of
      animal data to humans is discussed, including the current shortcomings of
      empirical scaling approaches and the lack of suitable mechanistic approaches.

PMID- 22619042
TI  - Anti-inflammatory sesquiterpene lactones from Lychnophora trichocarpha Spreng.
      (Brazilian Arnica).
AB  - The aerial parts of Lychnophora trichocarpha Spreng. (Asteraceae) are used
      macerated in water or ethanol to treat inflammation, pain, rheumatism,
      contusions, bruises and insect bites in Brazilian traditional medicine. In this
      study, anti-inflammatory activity of ethanol extract from aerial parts of L.
      trichocarpha and its ethyl acetate fraction was investigated. Sesquiterpene
      lactones, lychnopholide (Lyc) and eremantholide C (EreC), isolated of ethyl
      acetate fraction, were also assayed for in vitro and in vivo anti-inflammatory
      activity. Topical treatment with ointments containing ethanol extract, its ethyl
      acetate fraction and sesquiterpene lactones significantly reduced carrageenan
      induced mice paw oedema. In vitro assays demonstrated that Lyc inhibited
      interferon -gamma/lipopolysaccharide -stimulated nitric oxide (NO) production in
      J774A.1 macrophages and increased production of IL-10 anti-inflammatory cytokine.
      The reduction of tumor necrosis factor-alpha (TNF-alpha) production by EreC was
      accompanied by an increased production of IL-10 in a concentration-dependent
      manner in J774A.1 macrophages. The anti-inflammatory effect of Lyc seems to
      involve the inhibition of production of NO and increased production of IL-10. The
      mechanism of the effect of EreC on the reduction of carrageenan-induced paw
      oedema may be attributed to inhibition of production of TNF-alpha and stimulation
      of IL-10 production. The results corroborate the use of ethanol extract from
      Lychnophora trichocarpha in folk medicine for anti-inflammatory action and
      indicate that the topical route is suitable for use.

PMID- 22619043
TI  - Conservation of chromosomes syntenic with avian autosomes in squamate reptiles
      revealed by comparative chromosome painting.
AB  - In contrast to mammals, birds exhibit a slow rate of chromosomal evolution. It is
      not clear whether high chromosome conservation is an evolutionary novelty of
      birds or was inherited from an earlier avian ancestor. The evolutionary
      conservatism of macrochromosomes between birds and turtles supports the latter
      possibility; however, the rate of chromosomal evolution is largely unknown in
      other sauropsids. In squamates, we previously reported strong conservatism of the
      chromosomes syntenic with the avian Z, which could reflect a peculiarity of this
      part of the genome. The chromosome 1 of iguanians and snakes is largely syntenic
      with chromosomes 3, 5 and 7 of the avian ancestral karyotype. In this project, we
      used comparative chromosome painting to determine how widely this synteny is
      conserved across nine families covering most of the main lineages of Squamata.
      The results suggest that the association of the avian ancestral chromosomes 3, 5
      and 7 can be dated back to at least the early Jurassic and could be an ancestral
      characteristic for Unidentata (Serpentes, Iguania, Anguimorpha, Laterata and
      Scinciformata). In Squamata chromosome conservatism therefore also holds for the
      parts of the genome which are homologous to bird autosomes, and following on from
      this, a slow rate of chromosomal evolution could be a common characteristic of
      all sauropsids. The large evolutionary stasis in chromosome organization in birds
      therefore seems to be inherited from their ancestors, and it is particularly
      striking in comparison with mammals, probably the only major tetrapod lineage
      with an increased rate of chromosomal rearrangements as a whole.

PMID- 22619044
TI  - The utility of end-of-treatment bone marrow aspirates in pediatric acute
      lymphoblastic leukemia: a quality improvement project.
AB  - We reviewed the use, results and costs of end-of-treatment bone marrow aspirates
      (EOTBMAs) performed locally in patients diagnosed with ALL between 2000 and 2005.
      Of 193 patients, 188(97%) received EOTBMAs. Though 15/188(8.0%) patients
      experienced relapse at a median time of 1.1 years (range 0.1-4 years), no sign of
      relapse was detected on any EOTBMA. After communication of results to clinical
      staff, only 2/17 (12%) of patients with ALL finishing treatment in the subsequent
      5 months received an EOTBMA (P < 0.0001). Our results confirm the futility of
      EOTBMAs in a large contemporary cohort. Disseminating local results may help
      ensure adherence to best practices.

PMID- 22619046
TI  - Preclinical cadaveric study of transanal endoscopic da Vinci(r) surgery.
AB  - BACKGROUND: Single-port platforms are increasingly being used for transanal
      surgery and may be associated with a shorter learning curve than transanal
      endoscopic microsurgery. However, these procedures remain technically
      challenging, and robotic technology could overcome some of the limitations and
      increase intraluminal manoeuvrability. An initial experimental experience with
      transanal endoscopic da Vinci((r)) surgery (TEdS) using a glove port on human
      cadavers is reported. METHODS: After initial dry laboratory experiments, the
      feasibility of TEdS and ideal set-up were further evaluated in human cadavers.
      For transanal access a glove port was constructed on-table by using a circular
      anal dilator, a standard wound retractor and a surgical glove. A da Vinci((r)) Si
      HD system was used in combination with the glove port for transanal endoscopic
      resections. RESULTS: It was possible to perform all necessary tasks to complete a
      full-thickness excision and closure of the rectal wall, with cadavers in both
      prone and supine positions. The stable magnified view, combined with the
      EndoWrist((r)) technology of the robotic instruments, made every task
      straightforward. Intraluminal manoeuvrability could be improved further by
      intersecting the robotic instruments. The glove port proved to be very reliable
      and the inherent flexibility of the glove facilitated docking of the robotic arms
      in a narrow confined space. CONCLUSION: Using a reliable and universally
      available glove port, TEdS was feasible and a preferred set-up was determined.
      Further clinical trials will be necessary to assess the safety and efficacy of
      this technique.

PMID- 22619045
TI  - Development of budesonide nanocluster dry powder aerosols: formulation and
      stability.
AB  - The physical and chemical stability of dry powder aerosol formulations is an
      essential component in the development of an inhaled therapeutic. The
      pharmaceutical processing methods and storage conditions are primary determinants
      of the stability of a dry powder inhaler (DPI) formulation. Wet milling was used
      to produce budesonide NanoClusters (NCs), which are agglomerates of drug
      nanoparticles (~ 300 nm) with a mean aerodynamic diameter between 1 and 3 um,
      capable of deep lung penetration. In this study, the reproducibility of NC
      processing and performance was established. The physical stability of a selected
      budesonide NC formulation was investigated using industry standard dose content
      uniformity and cascade impaction techniques. The chemical stability of the lead
      formulation was also determined as a function of processing parameters and
      storage conditions. This study confirms the reproducibility and robust stability
      of NC powders as a novel means to turn drug particles into high-performance
      aerosols.

PMID- 22619047
TI  - Pain-related catastrophizing: we know it is important but why and how can we
      change it?: commentary on a paper by de Boer et al. (this issue).

PMID- 22619048
TI  - Role of interleukin-30 as a modulator of transcription signaling in liver injury.

PMID- 22619049
TI  - Several mechanisms lead to the inactivation of the CDKN2A (P16), P14ARF, or
      CDKN2B (P15) genes in the GCB and ABC molecular DLBCL subtypes.
AB  - Diffuse large B-cell lymphoma (DLBCL) represents the most frequent type of
      aggressive lymphoma. Deletions of the CDKN2A locus, encoding the proteins CDKN2A
      (P16), P14ARF, and of the CDKN2B locus, encoding the protein CDKN2B (P15), affect
      one-third of DLBCL patients. Although other mechanisms that decrease gene
      expression have been reported, such as promoter methylation, the prognostic value
      of these mechanisms is still unclear. We studied the deletion and methylation
      status of these genes in 171 patients and correlated the genomic results with
      their mRNA expression level and clinical outcome. CDKN2A, P14ARF, and CDKN2B
      deletions were significantly correlated with decreased mRNA expression (P<0.0001,
      P<0.0001, and P=0.0148, respectively). P14ARF was methylated in only two patients
      (1.3%), whereas CDKN2A and CDKN2B were methylated in 36.7 and 31.4% of patients,
      respectively. Methylation levels greater than 25% were associated with decreased
      expression of CDKN2A (P=0.0169). CDKN2A and CDKN2B inactivation by deletion or
      methylation was observed in 42.7 and 37.4% of cases, respectively. Including
      P14ARF deletions, we identified an inactivating mechanism for at least one of
      these genes in 47% of patients. Although gene inactivation was not correlated
      with the international prognostic index, P14ARF and CDKN2B inactivation was
      significantly associated with shorter survival (P=0.0048 and P=0.0413,
      respectively), whereas CDKN2A was not (P=0.085). Low mRNA expression levels of
      these genes were correlated with the ABC phenotype. Furthermore, our results show
      that an inactivating methylation was more frequent in the GCB phenotype.

PMID- 22619050
TI  - Concurrent radiation with irinotecan and carboplatin in intermediate- and high
      risk rhabdomyosarcoma: a report on toxicity and efficacy from a prospective pilot
      phase II study.
AB  - BACKGROUND: Irinotecan is highly active against rhabdomyosarcoma (RMS), yet its
      tolerability and efficacy in combination with radiation is unknown. We examined
      local control and toxicities in RMS patients treated with radiotherapy (RT) in
      combination with radiosensitizing agents irinotecan + carboplatin (I + C).
      PROCEDURE: From 11/2003 to 1/2011, 60 patients were enrolled on a pilot phase II
      protocol with newly diagnosed intermediate- or high-risk RMS at Memorial Sloan
      Kettering Cancer Center. Induction therapy consisted of two cycles of I + C
      followed by three cycles of vincristine, doxorubicin, and cyclophosphamide. At
      week 13, 47 patients received definitive primary-site RT or post-operative RT
      with two concurrent cycles of I + C. Median RT dose was 50.4 Gy (range 30.6-50.4
      Gy). Radiation-related toxicities were evaluated according to the Common
      Terminology Criteria for Adverse Events, version 3.0. RESULTS: Median age of the
      cohort was 9 years. With median follow-up of 32 months, 2.5 year actuarial local
      control was 89%. Among all patients, grades 3 and 4 dermatitis were observed in
      11% and 4%, respectively. Among parameningeal, orbit, and other head/neck sites,
      rates of grades 3 and 4 mucositis were 20% and 10%, respectively. Among
      abdomen/pelvis sites, 12% developed grade 3 diarrhea and 6% developed grade 3
      cystitis. No treatment breaks were necessary. CONCLUSIONS: Preliminary results of
      irinotecan and carboplatin administered with concurrent RT in intermediate- and
      high-risk RMS demonstrated favorable tolerability, efficacy, and local control.
      Reduced rates of acute grades 3-4 mucositis were observed when compared with
      historical results.

PMID- 22619051
TI  - Polyoxometalates immobilized in ordered mesoporous carbon nitride as highly
      efficient water oxidation catalysts.
AB  - Support with pom poms: A hybrid material ([Co(4)(H(2)O)(2)(PW(9)O(34))(2)](10
      )/mesoporous carbon nitride) is prepared as an efficient water oxidation
      catalyst, and shows excellent catalytic activity for water oxidation. Mesoporous
      carbon nitride as an immobilization matrix improves the catalytic water oxidation
      activity and structural durability of the assembled nanostructures.

PMID- 22619052
TI  - Natural flavone jaceosidin is a neuroinflammation inhibitor.
AB  - Jaceosidin is a naturally occurring flavone with pharmacological activity.
      Jaceosidin, as one of the major constituents of the medicinal herbs of the genus
      Artemisia, has been shown to exert anticancer, anti-oxidative, anti-inflammatory,
      and immunosuppressive effects. This study was undertaken to determine the effect
      of jaceosidin on microglia and neuroinflammation. Microglia are the innate immune
      cells in the central nervous system, and they play a central role in the
      initiation and maintenance of neuroinflammation. We report that jaceosidin
      inhibits inflammatory activation of microglia, reducing nitric oxide (NO)
      production and proinflammatory cytokine expression. IC50 for NO inhibition was 27
      +/- 0.4 MUM. The flavone also attenuated microglial neurotoxicity in the
      microglia/neuroblastoma co-culture. Systemic injection of jaceosidin ameliorated
      neuroinflammation in the mouse model of experimental allergic encephalomyelitis.
      These results indicate that plant flavone jaceosidin is a microglial inhibitor
      with anti-neuroinflammation activity.

PMID- 22619053
TI  - Correlates of tumor development in patients with myotonic dystrophy.
AB  - Patients with myotonic dystrophy (DM) have recently been reported to be at
      increased risk of tumor development, but clinical associations related to this
      observation are unknown. We calculated the odds ratios (ORs) and 95 % confidence
      intervals (CI) of self-reported tumor development by patients' demographic and
      clinical characteristics to evaluate factors associated with tumor development in
      DM patients, using data from the National Registry of Myotonic Dystrophy and
      Facioscapulohumeral Dystrophy Patients and Family Members. Of the 911
      participants, 47.5 % were male and 85.7 % had DM type 1 (DM1). Compared to DM1,
      patients with DM type 2 (DM2) were older at registry enrollment (median age 55
      vs. 44 years, p < 0.0001) and at DM diagnosis (median age 48 vs. 30 years, p <
      0.0001); and more likely to be females (p = 0.001). At enrollment, 95 (10.4 %) DM
      patients reported a history of benign or malignant tumor. Tumors were associated
      with female gender (OR 1.9, 95 % CI 1.2-3.1, p = 0.007) and DM1 (OR 2.1, 95 % CI
      1.1-4.1, p = 0.03). In a subgroup analysis of patients with blood-based DNA
      testing results (397 DM1, 54 DM2), repeat expansion size was not associated with
      tumor risk in DM1 (p = 0.26) or DM2 (p = 0.34). In conclusion, female gender and
      DM1 subtype, but not DNA repeat expansion size, were associated with increased
      risk of tumors in DM. Follow-up studies are warranted to determine if oncogenes
      associated with dystrophia myotonica-protein kinase are altered in DM, and to
      determine if repeat expansion size, as in our study, is not associated with tumor
      development.

PMID- 22619054
TI  - Genetic testing in neurological diseases.
AB  - The advances in sequencing technologies and the availability of molecular testing
      for a rapidly increasing number of diseases are both promising and challenging.
      Here, we will focus on practical aspects and the usefulness of molecular
      diagnosis in a clinical setting. Even in the absence of therapeutic consequences,
      genetic testing can and should be considered for a number of reasons, including a
      right to know for the patient and the family, and the avoidance of further
      diagnostic work-up. As it will soon become possible to routinely sequence
      hundreds or even thousands of genes in parallel, molecular diagnosis will become
      increasingly important as it provides valuable information for the physician and
      for the affected individuals.

PMID- 22619055
TI  - Adult-onset Alexander disease with an R66Q mutation in GFAP presented with severe
      vocal cord paralysis during sleep.

PMID- 22619056
TI  - Lower motor neuron disease caused by a novel FUS/TLS gene frameshift mutation.

PMID- 22619057
TI  - ZASPopathy with childhood-onset distal myopathy.
AB  - We report on a German family presenting with a predominantly distal myopathy
      primarily affecting anterior compartments of lower legs in childhood. Proximal
      lower limb and hip girdle weakness developed later in early adulthood in the
      female index patient and likewise in her mother. Consecutive muscle biopsy
      findings were first attributed to a mild congenital myopathy and later on
      interpreted as neurogenic changes without clear signs of a myopathy. Molecular
      genetic analysis was performed because of the clinical impression of a distal
      myopathy combined with dominant inheritance. The heterozygous mutation c.349G>A
      (p.D117N) in the ZASP gene could be found. This mutation had been previously
      associated with an adult-onset, isolated, dilated left ventricular non-compaction
      cardiomyopathy (OMIM*605906.0007), which was not present in our patients. Our
      data show that this mutation can be associated with an isolated skeletal muscle
      phenotype. Second, mutation analysis of the ZASP gene is suggested for distal
      myopathies of any age, even in cases of uncharacteristic muscle biopsy findings
      on routine analysis.

PMID- 22619058
TI  - Association of obesity with cerebral microbleeds in neurologically asymptomatic
      elderly subjects.
AB  - Obesity is associated with an increased risk of cardiovascular disease, but few
      studies have investigated the effects of obesity on subclinical cerebrovascular
      disease. Cerebral microbleeds (CMBs) are radiological markers of cerebral small
      vessel disease and reflect underlying vasculopathy. In this context, we assessed
      whether obesity was related to CMBs and to CMB subtypes categorized by location.
      Neurologically asymptomatic elderly subjects (n = 1,251; age >= 65 years) who
      visited for routine health check-ups were included in this study. Cerebral
      microbleeds were evaluated through T2*-weighted gradient-recalled echo MRI. The
      subjects were categorized into two groups depending on CMB location: strictly
      lobar and deep or infratentorial microbleeds. Body mass index was calculated, and
      obesity was defined using the World Health Organization Western Pacific Regional
      Office criteria. A total of 120 (9.6 %) subjects were found to have CMBs. As the
      severity of obesity increased, the prevalence of CMBs increased. Compared with
      the normal weight group and after controlling possible confounders, the risk of
      deep or infratentorial microbleeds was significantly increased in the overweight
      group [odds ratio (OR) 2.32, 95 % confidence interval (CI) 1.19-4.53], and the
      obese group (OR 2.17, 95 % CI 1.14-4.13). However, the ORs for the strictly lobar
      microbleeds were not increased in either the overweight or obese groups. Obesity
      was associated with deep or infratentorial microbleeds. This finding suggests
      that obesity affects cerebral small vessels through arteriosclerotic
      vasculopathy. Based on our findings, we postulate that obesity is associated with
      the presence of subclinical and bleeding-prone cerebrovascular disease in the
      elderly.

PMID- 22619059
TI  - Breastfeeding and multiple sclerosis relapses: a meta-analysis.

PMID- 22619060
TI  - Stem cells: from animal models to clinical practice.

PMID- 22619061
TI  - Sodium-23 solid-state nuclear magnetic resonance of commercial sodium naproxen
      and its solvates.
AB  - We report on the investigation of sodium coordination environments with solid
      state 23Na nuclear magnetic resonance (NMR) spectroscopy of various hydrates and
      solvates of sodium naproxen (SN), a commercially available anti-inflammatory drug
      sold over the counter as Aleve(r), among other names. The 23Na quadrupolar
      coupling constant is found to change significantly depending on the hydration
      state, and subtle changes in oxygen coordination environment about the sodium
      cations were apparent in the NMR spectra. High-resolution double-rotation NMR
      experiments are also performed on powdered samples to obtain solution-like 23Na
      NMR spectra. Our attempts at crystallizing various solvates of SN have led to the
      characterization of the first crystal structure for the heminonahydrated form.
      The composition of commercial SN is also investigated and it is shown that
      Aleve(r) is composed of approximately 80% monohydrate solvate. Density-functional
      theory calculations, using the gauge-including projector-augmented-wave
      formalism, allow for the assignment of 23Na NMR peaks to specific sodium sites in
      the reported X-ray crystal structure.

PMID- 22619062
TI  - Systematic review and meta-analysis of vein cuffs for below-knee synthetic
      bypass.
AB  - BACKGROUND: The aim was to investigate the possible benefit of vein cuffs for
      femoral to below-knee popliteal and femorodistal vessel synthetic bypass grafts.
      METHODS: PubMed, the Cochrane library, Embase and ClinicalTrials.gov were
      searched for all studies on any clinical effect of vein cuffs on synthetic
      grafts. Outcomes were selected based on inclusion in two or more studies: primary
      patency and limb survival. The data were subjected to meta-analysis by outcome.
      RESULTS: Three cohort and two randomized studies were selected for inclusion,
      involving 885 patients. Meta-analysis of five studies examining below-knee
      popliteal bypass showed a significant improvement for primary patency in cuffed
      grafts at 2 years, but not at 1 or 3 years (odds ratio at 2 years 0.46, 95 per
      cent confidence interval 0.22 to 0.97; P = 0.04). Limb salvage was significantly
      improved in cuffed grafts up to 2 years. Limb survival was also improved for
      cuffed distal grafts at 2 years (odds ratio 0.29, 0.11 to 0.75; P = 0.01) but
      showed no difference at any other time interval. Study quality was generally
      poor, with conflicting results. CONCLUSION: There was a small but significant
      benefit for vein cuffs on synthetic grafts used for femoral to below-knee
      popliteal anastomoses, but little benefit for femorodistal anastomoses.

PMID- 22619063
TI  - Refinement of stopping rules during treatment of hepatitis C genotype 1 infection
      with boceprevir and peginterferon/ribavirin.
AB  - In comparison with peginterferon/ribavirin alone, boceprevir with
      peginterferon/ribavirin significantly improves sustained virological response
      (SVR) rates in patients with chronic hepatitis C virus (HCV) genotype 1
      infections, but treatment failure remains a significant problem. Using phase 3
      trial databases, we sought to develop stopping rules for patients destined to
      fail boceprevir-based combination therapy in order to minimize drug toxicity,
      resistance, and costs in the face of ultimate futility. Exploratory post hoc
      analyses using data from the Serine Protease Inhibitor Therapy 2 (SPRINT-2) study
      (treatment-naive patients) and the Retreatment With HCV Serine Protease Inhibitor
      Boceprevir and Pegintron/Rebetol 2 (RESPOND-2) study (treatment-experienced
      patients) were undertaken to determine whether protocol-specified stopping rules
      (detectable HCV RNA at week 24 for SPRINT-2 and at week 12 for RESPOND-2) could
      be refined and harmonized. In SPRINT-2, a week 12 rule with an HCV RNA cutoff of
      >= 100 IU/mL would have discontinued therapy in 65 of 195 failures (sensitivity =
      33%) without sacrificing a single SVR among 475 successes (specificity = 100%).
      Viral variants emerged after week 12 in 36 of the 49 evaluable patients (73%) who
      would have discontinued at week 12 using a >= 100 IU/mL stopping rule. In RESPOND
      2, five of six patients with week 12 HCV RNA levels between the lower limit of
      detection (9.3 IU/mL) and the lower limit of quantification (25 IU/mL) who
      continued therapy despite the protocol-stipulated futility rule achieved SVR; one
      additional patient with a week 12 HCV RNA level of 148 IU/mL also continued
      therapy, had undetectable HCV RNA at week 16, and attained SVR. CONCLUSION:
      Although a stopping rule of detectable HCV RNA at week 12 would have forfeited
      some SVR cases, week 12 HCV RNA levels >= 100 IU/mL almost universally predicted
      a failure to achieve SVR in both treatment-naive and treatment-experienced
      patients. In boceprevir recipients, the combination of 2 stopping rules-an HCV
      RNA level >= 100 IU/mL at week 12 and detectable HCV RNA at week 24--maximized
      the early discontinuation of futile therapy and minimized premature treatment
      discontinuation.

PMID- 22619064
TI  - A biomimetic domino reaction for the concise synthesis of capreomycidine and
      epicapreomycidine.
AB  - The non-proteinogenic amino acids capreomycidine and epicapreomycidine are
      constituents of antibiotically active natural products, but the synthesis of
      these unusual cyclic guanidine derivatives is challenging. The biosynthesis of
      capreomycidine has therefore been employed as a guideline to develop a concise
      biomimetic synthesis of both epimeric amino acids. The resulting domino
      guanidinylation-aza-Michael-addition reaction provides the most convenient access
      to these amino acids in racemic form. Attempts to dissect the domino reaction
      into two separate transformations for a stereocontrolled version of this
      synthetic approach have also been made. The synthesized didehydro-arginine
      derivatives with urethane-protected guanidine moieties did not undergo the aza
      Michael-addition anymore. These results may have wider implications for the 1,4
      addition of guanidines to alpha,beta-unsaturated carbonyl compounds, particularly
      to didehydro amino acids.

PMID- 22619065
TI  - Taurine plays an important role in the protection of spermatogonia from oxidative
      stress.
AB  - It has been demonstrated that taurine has various physiological functions in the
      body. We demonstrated that taurine is abundant in the serum, liver, muscle and
      testis of the Japanese eel (Anguilla japonica). In the eel testis, taurine is
      found mainly in spermatogonia and is weakly expressed also in the Sertoli cells.
      We have further found in the eel testis that taurine is actively accumulated via
      the sodium/chloride-dependent taurine transporter (TauT; SLC6A6), which is
      expressed in germ cells. In our current study, the effects of taurine on the anti
      oxidant response were examined. Taurine was found to promote the total superoxide
      dismutase (SOD) activity in the testis. Moreover, our results indicate that
      taurine does not affect the mRNA levels of copper-zinc (Cu/Zn) SOD or manganese
      SOD, but promotes the translation of Cu/Zn SOD. Overall, our present data suggest
      that taurine may modulate Cu/Zn SOD at the translational level and thereby may
      play an important role in the protection of germ cells from oxidative stress.

PMID- 22619066
TI  - Ultrastructural and spectrophotometric study on the effects of putative triggers
      on aortic valve interstitial cells in in vitro models simulating metastatic
      calcification.
AB  - Metastatic calcification of cardiac valves is a common complication in patients
      affected by chronic renal failure. In this study, primary bovine aortic valve
      interstitial cells (AVICs) were subjected to pro-calcific treatments consisting
      in cell stimulation with (i) elevated inorganic phosphate (Pi = 3 mM), to
      simulate hyperphosphatemic conditions; (ii) bacterial endotoxin
      lipopolysaccharide (LPS), simulating direct effects by microbial agents; and
      (iii) conditioned media (CM) derived from cultures of either LPS-stimulated
      heterogenic macrophages (commercial murine RAW264.7 cells) or LPS-stimulated
      fresh allogenic monocytes/macrophages (bCM), simulating consequent inflammatory
      responses, alone or combined. Compared to control cultures, spectrophotometric
      assays revealed shared treatment-dependent higher values of both calcium amounts
      and alkaline phosphatase activity for cultures involving the presence of elevated
      Pi. Ultrastructurally, shared peculiar pro-calcific degeneration patterns were
      exhibited by AVICs from these latter cultures irrespectively of the additional
      treatments. Disappearance of all cytomembranes and concurrent formation of
      material showing positivity to Cuprolinic Blue and co-localizing with silver
      precipitation were followed by the outcropping of such a material, which
      transformed in layers outlining the dead cells. Subsequent budding of these
      layers resulted in the formation of bubbling bodies and concentrically laminated
      calcospherulae mirroring those in actual soft tissue calcification. In
      conclusion, the in vitro models employed appear to be reliable tools for
      simulating metastatic calcification and indicate that hyperphosphatemic-like
      conditions could trigger valve calcification per se, with LPS and allogenic
      macrophage-derived secretory products acting as possible calcific enhancers via
      inflammatory responses.

PMID- 22619067
TI  - GAS41 amplification results in overexpression of a new spindle pole protein.
AB  - Amplification is a hallmark of many human tumors but the role of most amplified
      genes in human tumor development is not yet understood. Previously, we identified
      a frequently amplified gene in glioma termed glioma-amplified sequence 41
      (GAS41). Using the TCGA data portal and performing experiments on HeLa and
      TX3868, we analyzed the role of GAS41 amplification on GAS41 overexpression and
      the effect on the cell cycle. Here we show that GAS41 amplification is associated
      with overexpression in the majority of cases. Both induced and endogenous
      overexpression of GAS41 leads to an increase in multipolar spindles. We showed
      that GAS41 is specifically associated with pericentrosome material. As result of
      an increased GAS41 expression we found bipolar spindles with misaligned
      chromosomes. This number was even increased by a combined overexpression of GAS41
      and a reduced expression of NuMA. We propose that GAS41 amplification may have an
      effect on the highly altered karyotype of glioblastoma via its role during
      spindle pole formation.

PMID- 22619068
TI  - An ethics code for pain.

PMID- 22619069
TI  - Dexamethasone-incorporated nanofibrous meshes for antiproliferation of smooth
      muscle cells: thermally induced drug-loading strategy.
AB  - Pluronic-immobilized nanofibrous meshes were tailored for thermally induced
      incorporation of dexamethasone. A diblock copolymer composed of poly(e
      caprolactone)-poly (ethyleneglycol) (NH(2)) (PCL-PEG (NH(2))) was electrospun to
      a nanofibrous mesh, and Pluronic was subsequently surface-immobilized on the mesh
      in aqueous phase. Surface-wettability analysis and (1)H NMR spectroscopy
      confirmed surface-decoration of nanofibrous meshes with Pluronic moieties
      depending on the blend ratios of PCL-PEG(NH(2)). Fluorescently-labeled micelles
      were incorporated in the nanofibrous meshes by temperature modulation and showed
      attenuated release profiles of the micelles were for 1 month. The suppression
      degree of drug-loaded micelle releases was proportional to the blend ratio of PCL
      PEG(NH(2)). Dexamethasone was formulated into micellar nanoaggregates, and the
      dexamethasone micelles-loaded nanofibrous meshes were used for antiproliferation
      studies of smooth muscle cells. Flow cytometric analysis of the arrested cells at
      a G(0)-G(1) phase revealed that the dexamethasone micelles-loaded nanofibrous
      meshes effectively controlled proliferation of the smooth muscle cells when cells
      were cultivated with the nanofibrous meshes. The antiproliferation effects of the
      nanofibrous meshes were closely correlated to the release profiles of the
      micelles from the nanofibrous meshes with different blend ratios. Thus,
      dexamethasone-incorporated nanofibrous meshes can be potentially used for
      treatments of restenosis after percutaneous transluminal coronary angioplasty.

PMID- 22619070
TI  - Tea tree oil-induced transcriptional alterations in Staphylococcus aureus.
AB  - Tea tree oil (TTO) is a steam distillate of Melaleuca alternifolia that
      demonstrates broad-spectrum antibacterial activity. This study was designed to
      document how TTO challenge influences the Staphylococcus aureus transcriptome.
      Overall, bioinformatic analyses (S. aureus microarray meta-database) revealed
      that both ethanol and TTO induce related transcriptional alterations. TTO
      challenge led to the down-regulation of genes involved with energy-intensive
      transcription and translation, and altered the regulation of genes involved with
      heat shock (e.g. clpC, clpL, ctsR, dnaK, groES, groEL, grpE and hrcA) and cell
      wall metabolism (e.g. cwrA, isaA, sle1, vraSR and vraX). Inactivation of the heat
      shock gene dnaK or vraSR which encodes a two-component regulatory system that
      responds to peptidoglycan biosynthesis inhibition led to an increase in TTO
      susceptibility which demonstrates a protective role for these genes in the S.
      aureus TTO response. A gene (mmpL) encoding a putative resistance, nodulation and
      cell division efflux pump was also highly induced by TTO. The principal
      antimicrobial TTO terpene, terpinen-4-ol, altered ten genes in a transcriptional
      direction analogous to TTO. Collectively, this study provides additional insight
      into the response of a bacterial pathogen to the antimicrobial terpene mixture
      TTO.

PMID- 22619071
TI  - Pain assessment in premature infants treated with intravitreal antiangiogenic
      therapy for retinopathy of prematurity under topical anesthesia.
AB  - PURPOSE: To evaluate the physiological and behavioral pain response in premature
      infants receiving intravitreal bevacizumab injection (IVB) for retinopathy of
      prematurity (ROP) under topical anesthesia. METHODS: A prospective interventional
      non-comparative case series. Premature infants with high-risk prethreshold or
      threshold ROP received IVB using topical anesthesia with tetracaine eye drops. A
      Premature Infant Pain Profile was used to assess the pain response during the
      procedure. RESULTS: Nine premature infants requiring bilateral IVB therapy were
      included in the study. Mean gestational age was 28.7 +/- 1.3 weeks, and birth
      weight was 1,200 +/- 194 grams. The mean total pain score was found to be 8.7 +/-
      2.4 (range 5-14), indicating generally mild pain during the procedure. Eye
      squeeze was the most prominent indicator of pain. Most changes occurred at the
      beginning, with the insertion of the lid speculum and were hardly noted during
      the rest of the procedure including the injection itself. CONCLUSION: Topical
      anesthesia with tetracaine is an effective method for the relief of pain
      associated with intravitreal injections in premature infants with ROP.

PMID- 22619072
TI  - Using in situ pore water concentrations to estimate the phytotoxicity of
      nicosulfuron in soils to corn (Zea mays L.).
AB  - The phytotoxicity of an herbicide in soil is typically dependent on the soil
      characteristics. To obtain a comparable value of the concentration that inhibits
      growth by 50% (IC50), 0.01 M CaCl(2) , excess pore water (EPW) and in situ pore
      water (IPW) were used to extract the bioavailable fraction of nicosulfuron from
      five different soils to estimate the nicosulfuron phytotoxicity to corn (Zea mays
      L.). The results indicated that the phytotoxicity of nicosulfuron in soils to
      corn depended on the soil type, and the IC50 values calculated based on the
      amended concentration of nicosulfuron ranged from 0.77 to 9.77 mg/kg among the
      five tested soils. The range of variation in IC50 values for nicosulfuron was
      smaller when the concentrations of nicosulfuron extracted with 0.01 M CaCl(2) and
      EPW were used instead of the amended concentration. No significant difference was
      observed among the IC50 values calculated from the IPW concentrations of
      nicosulfuron in the five tested soils, suggesting that the concentration of
      nicosulfuron in IPW could be used to estimate the phytotoxicity of residual
      nicosulfuron in soils.

PMID- 22619073
TI  - Optimization of foliage photosynthetic capacity in tree canopies: towards
      identifying missing constraints.
AB  - Plant canopies are characterized by huge within-canopy gradients in environmental
      and physiological characteristics, but distributions of foliage photosynthetic
      capacity in plant canopies do not follow simple optimality criteria. Various
      hypotheses have been put forward to explain the lack of "optimality", including
      missing physiological and structural constraints and/or missing fundamental
      relationships. In this issue, Dewar et al. (2012) highlight important optimality
      constraints due to finite minimum leaf dry mass per unit area the plants can
      achieve, while Peltoniemi et al. (2012) proposes that limited acclimation of
      hydraulic conductance to within-canopy light conditions is a key missing factor
      in canopy optimality. This commentary advocates that future large-scale model
      exercises need to introduce more realism in model predictions both by including
      hydraulic controls as well as consider additional constraints shaping foliage
      structure, chemistry and physiological activity.

PMID- 22619074
TI  - Why does leaf nitrogen decline within tree canopies less rapidly than light? An
      explanation from optimization subject to a lower bound on leaf mass per area.
AB  - A long-established theoretical result states that, for a given total canopy
      nitrogen (N) content, canopy photosynthesis is maximized when the within-canopy
      gradient in leaf N per unit area (N(a)) is equal to the light gradient. However,
      it is widely observed that N(a) declines less rapidly than light in real plant
      canopies. Here we show that this general observation can be explained by optimal
      leaf acclimation to light subject to a lower-bound constraint on the leaf mass
      per area (m(a)). Using a simple model of the carbon-nitrogen (C-N) balance of
      trees with a steady-state canopy, we implement this constraint within the
      framework of the MAXX optimization hypothesis that maximizes net canopy C export.
      Virtually all canopy traits predicted by MAXX (leaf N gradient, leaf N
      concentration, leaf photosynthetic capacity, canopy N content, leaf-area index)
      are in close agreement with the values observed in a mature stand of Norway
      spruce trees (Picea abies L. Karst.). An alternative upper-bound constraint on
      leaf photosynthetic capacity (A(sat)) does not reproduce the canopy traits of
      this stand. MAXX subject to a lower bound on m(a) is also qualitatively
      consistent with co-variations in leaf N gradient, m(a) and A(sat) observed across
      a range of temperate and tropical tree species. Our study highlights the key role
      of constraints in optimization models of plant function.

PMID- 22619075
TI  - Simulation reveals two major docking pathways between the hexapeptide GDYMNM and
      the catalytic domain of the insulin receptor protein kinase.
AB  - Extending a previous mining-minima approach to identifying the docking pathways
      between the hexapeptide GDYMNM and the catalytic domain of the insulin receptor
      tyrosine kinase (IRK), we found two major docking pathways connecting the binding
      pocket and the surface of the protein. One pathway was more likely to lead to
      phosphate transfer from ATP to the peptide as the distance between the gamma
      phosphate of ATP and the hydroxyl oxygen of the target tyrosine approached one
      that could facilitate reaction. The movement of the peptide along the pathways
      was found to couple with residues in the activation loop of the protein. Although
      these residues might not affect binding affinity, they might influence the
      kinetics of peptide entrance and release.

PMID- 22619077
TI  - Superstaging in colorectal cancer.

PMID- 22619076
TI  - An intravaginal ring for the simultaneous delivery of multiple drugs.
AB  - Intravaginal delivery of microbicide combinations is a promising approach for the
      prevention of sexually transmitted infections, but requires a method of providing
      simultaneous, independent release of multiple agents into the vaginal
      compartment. A novel intravaginal ring (IVR) platform has been developed for
      simultaneous delivery of the reverse-transcriptase inhibitor tenofovir (TFV) and
      the guanosine analogue antiviral acyclovir (ACV) with independent control of
      release rate for each drug. The IVR is based on a pod design, with up to 10
      individual polymer-coated drug cores embedded in the ring releasing through
      preformed delivery channels. The release rate from each pod is controlled
      independently of the others by the drug properties, polymer coating, and size and
      number of delivery channels. Pseudo-zero-order in vitro release of TFV (144 +/-
      10 ug day) and ACV (120 +/- 19 ug day-1) from an IVR containing both drugs was
      sustained for 28 days. The mechanical properties of the pod IVR were evaluated
      and compared with the commercially available Estring(r) (Pfizer, NY, NY). The pod
      IVR design enables the vaginal delivery of multiple microbicides with differing
      physicochemical properties, and is an attractive approach for the sustained
      intravaginal delivery of relatively hydrophilic drugs that are difficult to
      deliver using conventional matrix IVR technology.

PMID- 22619078
TI  - Toenail selenium and incidence of type 2 diabetes in U.S. men and women.
AB  - OBJECTIVE: Compelling biological pathways suggest that selenium (Se) may lower
      onset of type 2 diabetes mellitus (T2DM), but very few studies have evaluated
      this relationship, with mixed results. We examined the association between
      toenail Se and incidence of T2DM. RESEARCH DESIGN AND METHODS: We performed
      prospective analyses in two separate U.S. cohorts, including 3,630 women and
      3,535 men, who were free of prevalent T2DM and heart disease at baseline in 1982
      1983 and 1986-1987, respectively. Toenail Se concentration was quantified using
      neutron activation analysis, and diabetes cases were identified by biennial
      questionnaires and confirmed by a detailed supplementary questionnaire. Hazard
      ratios of incident T2DM according to Se levels were calculated using Cox
      proportional hazards. RESULTS: During 142,550 person-years of follow-up through
      2008, 780 cases of incident T2DM occurred. After multivariable adjustment, the
      risk of T2DM was lower across increasing quintiles of Se, with pooled relative
      risks across the two cohorts of 1.0 (reference), 0.91 (95% CI 0.73-1.14), 0.78
      (0.62-0.99), 0.72 (0.57-0.91), and 0.76 (0.60-0.97), respectively (P for trend =
      0.01). Results were similar excluding the few individuals (4%) who used Se
      supplements. In semiparametric analyses, the inverse relationship between Se
      levels and T2DM risk appeared to be linear. CONCLUSIONS: At dietary levels of
      intake, individuals with higher toenail Se levels are at lower risk for T2DM.
      Further research is required to determine whether varying results in this study
      versus prior trials relate to differences in dose, source, statistical power,
      residual confounding factors, or underlying population risk.

PMID- 22619079
TI  - Effect of elevated basal insulin on cancer incidence and mortality in cancer
      incident patients: the Israel GOH 29-year follow-up study.
AB  - OBJECTIVE: Diabetes is associated with many forms of cancer. Recent evidence has
      suggested that some treatments for diabetes are associated with an increased
      cancer risk. Less is known about the association between endogenous insulin in
      the prediabetes state and cancer risk. RESEARCH DESIGN AND METHODS: We
      investigated cumulative cancer incidence and cancer incidence density over 29
      years, according to basal insulin, in a cohort of 1,695 nondiabetic men and women
      of four ethnic origins, aged 51.8 +/- 8.0 years at baseline. Total mortality
      among the 317 subjects (18.7%) who developed cancer at least 2 years after
      baseline was assessed. RESULTS: In a Cox proportional hazards model, the all-site
      hazard ratio of cancer incidence comparing the highest insulin quartile with the
      other three quartiles was 1.09 (95% CI 0.85-1.40), adjusted for age, sex, and
      ethnicity. BMI, smoking, and fasting blood glucose were not statistically
      significant in this model. Basal insulin level was not significantly associated
      with cancer of specific sites (breast, prostate, colon/rectum, or bladder).
      Fasting insulin in the upper quartile conferred a 37% increased risk for total
      mortality among cancer patients, adjusting for age, sex, and ethnic origin (95%
      CI 0.94-2.00, P = 0.097) compared with that of the lower quartiles. Male sex,
      older age, and North African origins were associated with a greater risk of
      mortality during follow-up time. CONCLUSIONS: This long-term cohort study may
      suggest a role for basal elevated insulin levels, mainly as a negative predictor
      in cancer prognosis.

PMID- 22619080
TI  - Racial/ethnic disparities in the prevalence of gestational diabetes mellitus by
      BMI.
AB  - OBJECTIVE: To examine whether the association between gestational diabetes
      mellitus (GDM) and BMI category varies by racial/ethnic group. RESEARCH DESIGN
      AND METHODS: In a cohort of 123,040 women without recognized pregravid diabetes
      who delivered babies between 1995 and 2006 at Kaiser Permanente of Northern
      California, we examined racial/ethnic disparities in the prevalence of GDM by BMI
      category and the population-attributable risk (PAR) associated with
      overweight/obesity. RESULTS: Among all racial/ethnic groups, the age-adjusted
      prevalence of GDM increased with increasing BMI (kg/m(2)) category. However,
      Asian and Filipina women had a prevalence of GDM of 9.9 and 8.5%, respectively,
      at a BMI of 22.0-24.9 kg/m(2), whereas in Hispanic, non-Hispanic white, and
      African American women, the prevalence of GDM was >8.0% at a higher BMI, such as
      28-30, 34-36, and >=37 kg/m(2), respectively. The estimated PARs suggest that the
      percentage of GDM that could be prevented if all pregnant women were of normal
      weight (BMI <25.0 kg/m(2)) ranging from 65% for African American women to only
      23% among Asian women. CONCLUSIONS: Clinicians should be aware that the BMI
      thresholds for increased risk of GDM varies by racial/ethnic group and that the
      risk is high even at relatively low BMI cutoffs in Asian and Filipina women.
      Asian women may benefit from different prevention strategies in addition to
      weight management.

PMID- 22619081
TI  - Area-level socioeconomic status and incidence of abnormal glucose metabolism: the
      Australian Diabetes, Obesity and Lifestyle (AusDiab) study.
AB  - OBJECTIVE: To examine the role of area-level socioeconomic status (SES) on the
      development of abnormal glucose metabolism (AGM) using national, population-based
      data. RESEARCH DESIGN AND METHODS: The Australian Diabetes, Obesity and Lifestyle
      (AusDiab) study is a national, population-based, longitudinal study of adults
      aged >=25 years. A sample of 4,572 people provided complete baseline (1999 to
      2000) and 5-year follow-up (2004 to 2005) data relevant for these analyses.
      Incident AGM was assessed using fasting plasma glucose and 2-h plasma glucose
      from oral glucose tolerance tests, and demographic, socioeconomic, and behavioral
      data were collected by interview and questionnaire. Area SES was defined using
      the Index of Relative Socioeconomic Disadvantage. Generalized linear mixed models
      were used to examine the relationship between area SES and incident AGM, with
      adjustment for covariates and correction for cluster design effects. RESULTS:
      Area SES predicted the development of AGM, after adjustment for age, sex, and
      individual SES. People living in areas with the most disadvantage were
      significantly more likely to develop AGM, compared with those living in the least
      deprived areas (odds ratio 1.53; 95% CI 1.07-2.18). Health behaviors (in
      particular, physical activity) and central adiposity appeared to partially
      mediate this relationship. CONCLUSIONS: Our findings suggest that characteristics
      of the physical, social, and economic aspects of local areas influence diabetes
      risk. Future research should focus on identifying the aspects of local
      environment that are associated with diabetes risk and how they might be
      modified.

PMID- 22619082
TI  - Improved biomedical and psychological outcomes 1 year after structured education
      in flexible insulin therapy for people with type 1 diabetes: the U.K. DAFNE
      experience.
AB  - OBJECTIVE: DAFNE (Dose Adjustment For Normal Eating), a structured education
      program in flexible insulin therapy, has been widely adopted in the U.K. after
      validation in a randomized trial. To determine benefits in routine practice, we
      collected biomedical and psychological data from all participants attending
      during a 12-month period. RESEARCH DESIGN AND METHODS: HbA(1c), weight, self
      reported hypoglycemia awareness, severe hypoglycemia frequency, PAID (Problem
      Areas In Diabetes), HADS (Hospital Anxiety and Depression Scale), and EuroQol
      Group 5-Dimension Self-Report Questionnaire scores were recorded prior to DAFNE
      and after 1 year. RESULTS: Complete baseline and follow-up HbA(1c) data were
      available for 639 (54.9%) of 1,163 attendees. HbA(1c) fell from 8.51 +/- 1.41
      (mean +/- SD) to 8.24 +/- 1.29% (difference 0.27 [95% CI 0.16-0.38]; P < 0.001),
      with a greater mean fall of 0.44% from baseline HbA(1c) >8.5%. Severe
      hypoglycemia rate fell from 1.7 +/- 8.5 to 0.6 +/- 3.7 episodes per person per
      year (1.1 [0.7-1.4]) and hypoglycemia recognition improved in 43% of those
      reporting unawareness. Baseline psychological distress was evident, with a PAID
      score of 25.2 and HADS scores of 5.3 (anxiety) and 4.8 (depression), falling to
      16.7 (8.5 [6.6-10.4]), 4.6 (0.7 [0.4-1.0]), and 4.2 (0.6 [0.3-0.8]), respectively
      (all P < 0.001 at 1 year). Clinically relevant anxiety and depression (HADS >= 8)
      fell from 24.4 to 18.0% and 20.9 to 15.5%, respectively. CONCLUSIONS: A
      structured education program delivered in routine clinical practice not only
      improves HbA(1c) while reducing severe hypoglycemia rate and restoring
      hypoglycemia awareness but also reduces psychological distress and improves
      perceived well-being.

PMID- 22619083
TI  - Depression predicts all-cause mortality: epidemiological evaluation from the
      ACCORD HRQL substudy.
AB  - OBJECTIVE: Depression affects up to 20-25% of adults with type 2 diabetes and may
      increase all-cause mortality, but few well-designed studies have examined the
      effects of depression on the full range of cardiovascular disease outcomes in
      type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 2,053 participants in
      the ACCORD (Action to Control Cardiovascular Risk in Diabetes) Health-Related
      Quality of Life substudy completed the Patient Health Questionnaire (PHQ)-9
      measure of depression symptoms at baseline and 12, 36, and 48 months. Cox
      proportional hazards regression models were used to estimate hazard ratios (HRs)
      (95% CI) for the time-varying impact of depression on protocol-defined clinical
      outcomes with and without adjustment for demographic, trial-related, clinical,
      and behavioral variables. RESULTS: In fully adjusted models, depression was not
      significantly related to the ACCORD primary composite outcome (cardiovascular
      death, nonfatal heart attack, or stroke) (HR 1.53 [95% CI 0.85-2.73]) or to the
      ACCORD microvascular composite outcome (0.93 [0.53-1.62]), but all-cause
      mortality was significantly increased both in those with PHQ-assessed probable
      major depression (2.24 [1.24-4.06]) and PHQ score of >= 10 (1.84 [1.17-2.89]).
      The effect of depression on all-cause mortality was not related to previous
      cardiovascular events or to assignment to intensive or standard glycemia control.
      Probable major depression (by PHQ-9) had a borderline impact on the ACCORD
      macrovascular end point (1.42 [0.99-2.04]). CONCLUSIONS: Depression increases the
      risk of all-cause mortality and may increase the risk of macrovascular events
      among adults with type 2 diabetes at high risk for cardiovascular events.

PMID- 22619084
TI  - Diabetes and lung cancer among postmenopausal women.
AB  - OBJECTIVE: Epidemiological evidence of diabetes as a lung cancer risk factor is
      limited and conflicting. Therefore, we assessed associations among diabetes,
      diabetes therapy, and lung cancer risk in postmenopausal women participating in
      the Women's Health Initiative (WHI) study. RESEARCH DESIGN AND METHODS:
      Postmenopausal women (n = 145,765), ages 50-79 years, including 8,154 women with
      diabetes at study entry were followed for a mean of 11 years with 2,257 lung
      cancers diagnosed. Information on diabetes therapy was collected via two methods
      (self-reported information on treatment history collected on a questionnaire at
      baseline and a face-to-face review of current medication containers that
      participants brought to the baseline visit). Lung cancers were confirmed by
      central medical record and pathology report review. Cox proportional hazards
      regression models adjusted for lung cancer risk factors were used to estimate
      hazard ratios (HRs) (95% CI) for diagnosis of diabetes and treatment of disease
      as risk factors for lung cancer. RESULTS: Compared with women without diabetes,
      women with self-reported treated diabetes had a significantly higher risk of lung
      cancer (HR 1.27 [95% CI 1.02-1.59]), with risks increasing for women with
      diabetes requiring insulin treatment (1.71 [1.15-2.53]). However, we did not
      observe a significant association between lung cancer risk and diabetes not
      treated with medication or with duration of diabetes. CONCLUSIONS: Postmenopausal
      women with treated diabetes, especially those using insulin, have a significantly
      higher risk of lung cancer. The influence of diabetes severity and specific
      classes of therapy for diabetes on lung cancer risk require future study.

PMID- 22619085
TI  - Look who's (not) talking: diabetic patients' willingness to discuss self-care
      with physicians.
AB  - OBJECTIVE: Nearly one-half of diabetic patients have glycated hemoglobin A(1c)
      (HbA(1c)) levels above recommended targets. Effective physician-patient
      communication improves glycemia and diabetes self-care; however, communication
      gaps may exist that prevent patients from discussing self-care problems with
      treatment providers. RESEARCH DESIGN AND METHODS: We assessed diabetic patients'
      (n = 316, 85% white, 51% female, 71% type 2 diabetes, 59 +/- 11 years old, 16 +/-
      3 years education, 19 +/- 13 years diabetes duration, and HbA(1c) = 7.9 +/- 1.4%)
      HbA(1c), frequency of self-care, diabetes-related distress, depressive and
      anxiety symptoms, coping styles, diabetes quality of life, and self-care
      communication in the treatment relationship. Multivariate logistic regression
      models examined the main and interaction effects of health and psychosocial
      factors associated with patients' reluctance to discuss self-care. RESULTS:
      Patients reported positive relationships with their doctors and valued honest
      communication; however, 30% of patients were reluctant to discuss self-care.
      Reluctant patients reported less frequent self-care (P = 0.05), lower diabetes
      quality of life (P = 0.002), and more diabetes-related distress (P = 0.001),
      depressive symptoms (P < 0.001), and anxiety symptoms (P = 0.001). Patients who
      reported elevated depressive symptoms, although not necessarily major depression,
      were more likely to be reluctant to discuss self-care (odds ratio [OR] 1.66 for
      10-point change in t score; P < 0.001), whereas patients who were older (OR 0.78
      for 10-year change; P = 0.05) and those who used more self-controlled coping
      styles (OR 0.78 for 10-point change; P = 0.007) were less likely to be reluctant.
      CONCLUSIONS: Awareness of elevated depressive symptoms is important in clinical
      practice given that these patients may be more reluctant to discuss self-care.
      Interventions and evidence-based approaches are needed to improve both depressive
      symptoms and physician-patient communication about self-care.

PMID- 22619086
TI  - Risk of hip fracture associated with hepatitis C virus infection and hepatitis
      C/human immunodeficiency virus coinfection.
AB  - Hepatitis C virus (HCV) infection has been associated with reduced bone mineral
      density, but its association with fracture rates is unknown, particularly in the
      setting of human immunodeficiency virus (HIV) coinfection. Our aims were to
      determine whether persons with HCV infection alone are at increased risk for hip
      fracture, compared to uninfected individuals, and to examine whether the risk of
      hip fracture is higher among HCV/HIV-coinfected persons, compared to those with
      HCV alone, those with HIV alone, and those uninfected with either virus. We
      conducted a cohort study in 36,950 HCV/HIV-coinfected, 276,901 HCV-monoinfected,
      95,827 HIV-monoinfected, and 3,110,904 HCV/HIV-uninfected persons within the U.S.
      Medicaid populations of California, Florida, New York, Ohio, and Pennsylvania
      (1999-2005). Incidence rates of hip fracture were lowest among uninfected persons
      (1.29 events/1,000 person-years), increased with the presence of either HIV
      infection (1.95 events/1,000 person-years) or HCV infection (2.69 events/1,000
      person-years), and were highest among HCV/HIV-coinfected individuals (3.06
      events/1,000 person-years). HCV/HIV coinfection was associated with an increased
      relative hazard (adjusted hazard ratio [HR] [95% confidence interval; CI]) of hip
      fracture, compared to HCV-monoinfected (HR, 1.38; 95% CI: 1.25-1.53), HIV
      monoinfected (females: HR, 1.76; 95% CI: 1.44-2.16; males: HR, 1.36; 95% CI: 1.20
      1.55), and HCV/HIV-uninfected persons (females: HR, 2.65; 95% CI: 2.21-3.17;
      males: HR, 2.20; 95% CI: 1.97-2.47). HCV monoinfection was associated with an
      increased risk of hip fracture, compared to uninfected individuals, and the
      relative increase was highest in the youngest age groups (females, 18-39 years:
      HR, 3.56; 95% CI: 2.93-4.32; males, 18-39 years: HR, 2.40; 95% CI: 2.02-2.84).
      CONCLUSION: Among Medicaid enrollees, HCV/HIV coinfection was associated with
      increased rates of hip fracture, compared to HCV-monoinfected, HIV-monoinfected,
      and HCV/HIV-uninfected persons. HCV-monoinfected patients had an increased risk
      of hip fracture, compared to uninfected individuals.

PMID- 22619087
TI  - Arctigenin anti-tumor activity in bladder cancer T24 cell line through induction
      of cell-cycle arrest and apoptosis.
AB  - Bladder cancer is the most common neoplasm in the urinary system. This study
      assesses arctigenin anti-tumor activity in human bladder cancer T24 cells in
      vitro and the underlying molecular events. The flow cytometry analysis was used
      to detect cell-cycle distribution and apoptosis. Western blotting was used to
      detect changes in protein expression. The data showed that arctigenin treatment
      reduced viability of bladder cancer T24 cells in a dose- and time-dependent
      manner after treatment with arctigenin (10, 20, 40, 80, and 100 MUmol/L) for 24
      hr and 48 hr. Arctigenin treatment clearly arrested tumor cells in the G1 phase
      of the cell cycle. Apoptosis was detected by hoechst stain and flow cytometry
      after Annexin-V-FITC/PI double staining. Early and late apoptotic cells were
      accounted for 2.32-7.01% and 3.07-7.35%, respectively. At the molecular level,
      arctigenin treatment decreased cyclin D1 expression, whereas CDK4 and CDK6
      expression levels were unaffected. Moreover, arctigenin selectively altered the
      phosphorylation of members of the MAPK superfamily, decreasing phosphorylation of
      ERK1/2 and activated phosphorylation of p38 significantly in a dose-dependent
      manner. These results suggest that arctigenin may inhibit cell viability and
      induce apoptosis by direct activation of the mitochondrial pathway, and the
      mitogen-activated protein kinase pathway may play an important role in the anti
      tumor effect of arctigenin. The data from the current study demonstrate the
      usefulness of arctigenin in bladder cancer T24 cells, which should further be
      evaluated in vivo before translation into clinical trials for the chemoprevention
      of bladder cancer.

PMID- 22619088
TI  - Aggregation and inactivation of pancreatic cystatin by riboflavin-derived singlet
      oxygen and flavin triplet state: polyphenols as preventive agents.
AB  - Caprine pancreatic thiol proteinase inhibitor (PTPI) a cystatin superfamily
      variant has high affinity for cysteine proteinases providing tight regulation of
      their proteolytic potential. Oxidative stress buildup in various pancreatic
      pathologies worsens the disease course often by disturbing the delicate balance
      between proteinases and their inhibitors. We aimed to study the effect of
      reactive oxygen species (ROS) on PTPI and to determine the potency of caffeic
      acid, curcumin and quercetin as agents against the inflicted damage. Fluorescence
      spectroscopy, polyacrylamide gel electrophoresis, and papain inhibitory assay
      revealed that photoilluminated riboflavin severely challenged the functional and
      structural integrity of the inhibitor. Three hundred and fifty micromolar affeic
      acid or quercetin prevented the damage. Curcumin, however, failed to reverse the
      changes completely. Conclusively, PTPI rendered dysfunctional by ROS may explain
      the increased necrotic damage to the host tissue. Also, dietary antioxidants can
      reverse the riboflavin-induced protein damage providing an economic and safe anti
      ROS therapy.

PMID- 22619089
TI  - Ecological risk assessment of parent and halogenated polycyclic aromatic
      hydrocarbons in surface sediments from an urban river in south China.
AB  - In the present study, 16 priority polycyclic aromatic hydrocarbons (Sigma(16)
      PAHs), including seven carcinogenic PAHs (Sigma(7) PAHs) designated by the U.S.
      Environmental Protection Agency, in surface sediment from an urban river
      (Shenzhen, south China) were measured. The concentrations of Sigma(16) PAHs and
      Sigma(7) PAHs ranged from 27.92 to 7409 ng/g and 0.53 to 2326 ng/g, respectively.
      Source appointments indicated that the PAHs in surface sediments were mainly
      derived from coal combustion (36.6%), oil spills (22.2%), vehicle emission
      (19.5%), and waste incineration (12.1%). The ecological risks posed by PAHs and
      several halogenated PAHs in these sediment samples were assessed using two
      redefined guidelines incorporating the toxic equivalency quotients (TEQs) of
      individual PAH congeners: (1) TEQs effect range-low, and (2) TEQs effect range
      median. The authors' results suggested that the PAHs they measured in most of the
      sediments in this urban river would not cause acute biological effects. On the
      contrary, the ecological risk posed by some halogenated PAHs was much higher than
      that of their corresponding parent PAHs. Finally, the relationships between PAH
      levels and catchment urbanization processes were examined. The results indicated
      that rapid urbanization has led to an obvious increase in PAH contamination in
      surface sediments.

PMID- 22619090
TI  - Sustained delivery of paclitaxel using thermogelling poly(PEG/PPG/PCL urethane)s
      for enhanced toxicity against cancer cells.
AB  - A multiblock poly(ether ester urethane)s comprising poly(epsilon-caprolactone),
      poly(ethylene glycol), and poly(propylene glycol) segments was synthesized. The
      aqueous copolymer solution exhibited thermogelling behavior at a critical
      gelation concentration of 3 wt %. The chemical structure and molecular
      characteristic of the copolymers were studied by gel permeation chromatography,
      NMR, and fourier transform infrared spectroscopy (FTIR). Rheological
      characterizations on the thermogel were carried out. Drug release studies using
      paclitaxel showed that sustained drug release of more than 2 weeks can be
      achieved with this system. The paclitaxel-loaded gels showed efficiency in the
      control of the growth of HeLa cells when compared with the paclitaxel dissolved
      in solution or paclitaxel encapsulated in Pluronics F127. The results
      demonstrated that the copolymers could be potentially used in chemotherapeutic
      applications.

PMID- 22619091
TI  - Oxygenation in cervical cancer and normal uterine cervix assessed using blood
      oxygenation level-dependent (BOLD) MRI at 3T.
AB  - Hypoxia is reported to be a biomarker for poor prognosis in cervical cancer.
      However, a practical noninvasive method is needed for the routine clinical
      evaluation of tumor hypoxia. This study examined the potential use of blood
      oxygenation level-dependent (BOLD) contrast MRI as a noninvasive technique to
      assess tumor vascular oxygenation at 3T. Following Institutional Review Board
      approved informed consent and in compliance with the Health Insurance Portability
      and Accountability Act, successful results were achieved in nine patients with
      locally advanced cervical cancer [International Federation of Gynecology and
      Obstetrics (FIGO) stage IIA to IVA] and three normal volunteers. In the first
      four patients, dynamic T2*-weighted MRI was performed in the transaxial plane
      using a multi-shot echo planar imaging sequence whilst patients breathed room air
      followed by oxygen (15 dm3/min). Later, a multi-echo gradient echo examination
      was added to provide quantitative R2* measurements. The baseline T2*-weighted
      signal intensity was quite stable, but increased to various extents in tumors on
      initiation of oxygen breathing. The signal in normal uterus increased
      significantly, whereas that in the iliacus muscle did not change. R2* responded
      significantly in healthy uterus, cervix and eight cervical tumors. This
      preliminary study demonstrates that BOLD MRI of cervical cancer at 3T is
      feasible. However, more patients must be evaluated and followed clinically before
      any prognostic value can be determined.

PMID- 22619092
TI  - Histological evaluation of bone healing using organic bovine bone in combination
      with platelet-rich plasma (an experimental study on rabbits).
AB  - OBJECTIVES: This study was carried out to histologically assess the effect of
      bone grafting materials extracted from bovine origin on the bone healing process
      either alone or when mixed with autologous platelet-rich plasma which could be
      used in many procedures of oral and maxillofacial bone and implant reconstructive
      surgery. MATERIALS AND METHODS: Sixteen rabbits were used; three intrabony
      defects in the femur bone of each rabbit were created, one left unfilled for
      normal healing process and served as control, the second filled with xenogenic
      graft (Gen-Ox-lyophilized bovine bone organic matrix), and the third filled with
      (Gen-Ox-lyophilized bovine bone organic matrix) mixed with autologous platelet
      rich plasma. Histological examination of the sections was performed after
      staining with H&E and Van Geison stains. The histomorphometric analysis including
      counting of bone cells (osteoblasts, osteocytes, and osteoclasts) with
      performance of osteon diameter and lamellar thickness at the end of the fourth
      week postoperatively was obtained. RESULTS: It has been shown that with the use
      of autologous platelet-rich plasma in combination with the xenogenic bone graft
      prepared from bovine origin, new bone formation and neovascularization were
      enhanced significantly when compared with xenogenic graft alone. CONCLUSION: The
      addition of PRP to xenogenic bone substitute in small bone defects of the rabbit
      femur showed a histomorphometric increase in bone formation (at the fourth week
      of healing). CLINICAL RELEVANCE: Platelet concentrate might be used to accelerate
      the osseointegration of enosseous dental implants.

PMID- 22619094
TI  - Different distribution of NOTCH1 mutations in chronic lymphocytic leukemia with
      isolated trisomy 12 or associated with other chromosomal alterations.
AB  - Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults in
      Western countries. Chromosomal abnormalities commonly found using conventional
      cytogenetics and FISH are del(11)(q22-23), trisomy 12, del(13)(q14), and
      del(17)(p13). Trisomy 12 is the most frequent numerical abnormality in CLL. It
      can appear isolated or associated with other chromosomal aberrations, including
      t(14;18)(q32;q21) and trisomy 18. The aim of this study was to determine whether
      CLL patients with isolated trisomy 12 or associated with other chromosomal
      alterations have different clinico-pathological features, including a different
      distribution NOTCH1 mutation. Patients were classified into four groups: Group 1,
      isolated trisomy 12 (n=14); Group 2, trisomy 12 plus trisomy 18 (n=4); Group 3,
      trisomy 12 plus t(14;18) (n=8); and Group 4: patients with trisomy 12 plus other
      abnormalities not involving BCL2 (n=28). The Binet stage and expression of ZAP70
      were significantly different among cytogenetic groups. NOTCH1 mutations were
      detected in 6/12 (50%) patients from Group 1, 4/25 (16%) patients from Group 4,
      and in no patient from groups 2 and 3 (P=0.020). Patients in Group 2 had a more
      rapid disease progression (median Treatment-free Survival 2 months) as against
      patients from Groups 1 (50 months), 3 (69 months), or 4 (68 months; P=0.001).
      These findings indicate that the distribution of NOTCH1 mutations in CLL with
      trisomy 12 is heterogeneous and that the presence of additional chromosomal
      abnormalities such as trisomy 18 could change the prognosis of these patients.

PMID- 22619093
TI  - Bond strength of self-adhesive resin cements to different treated indirect
      composites.
AB  - OBJECTIVES: The objective of this study was to determine microtensile bond
      strength (MUTBS) to dentin of three self-adhesive and a total-etch resin cements
      used for luting different treated indirect composites. MATERIALS AND METHODS:
      Composite overlays (Filtek Z250) were prepared. Their intaglio surfaces were
      ground with 600-grit SiC papers and randomly assigned to three different surface
      treatments: no treatment, silane application (RelyX Ceramic Primer), and silane
      agent followed by a bonding agent (Adper Scotchbond 1 XT). The composite overlays
      were luted to flat dentin surfaces of extracted human third molars using the
      following self-adhesive resin cements: RelyX Unicem, Maxcem Elite and G-Cem, and
      a total-etch resin cement, RelyX ARC. The bonded assemblies were stored in water
      (24 h, 37  degrees C) and subsequently prepared for MUTBS testing. Beams of
      approximately 1 mm(2) were tested in tension at 1 mm/min in a universal tester
      (Instron 3345). Data were analyzed by two-way ANOVA and Student-Newman-Keuls
      tests (alpha = 0.05). RESULTS: A significant influence of the resin cement used
      was detected. Composite surface treatment and the interaction between the resin
      cement applied and surface treatment did not affect MUTBS. CONCLUSIONS: Surface
      treatment of indirect resin composite did not improve the MUTBS results of
      dentin/composite overlay complex. Self-adhesive resin cements tested obtained
      lower MUTBS than the total-etch resin cement RelyX ARC. Specimens luted with
      Maxcem Elite exhibited the highest percentage of pretesting failures. CLINICAL
      RELEVANCE: Surface treatment of indirect resin composite with silane or silane
      followed by a bonding agent did not affect bond strength to dentin.

PMID- 22619095
TI  - Neuropathological aspects of conservative treatment of scoliosis. A theoretical
      view point.
AB  - An upright body posture cannot be maintained passively for reasons including a
      high location of the centre of gravity (COG) and a small support area. Proper
      alignment of body parts is maintained automatically, tending towards a pattern
      encoded in the CNS. A particularly important role in posture regulation is played
      by the short muscles of the back, which respond to being stretched with a
      contraction. During the early phase of scoliosis, the CNS automatically corrects
      abnormalities, but over time habituation occurs and the CNS treats them as
      something normal. Any attempt to restore proper body alignment is treated as an
      error and CNS automatically restores this abnormal pattern. With a prolonged
      deviation in body part alignment, CNS treats it as a defect and runs compensatory
      mechanisms to restore the balance of the body as a whole. Balance is ensured by
      postural compensation, but this does not restore proper body part alignment. In
      the treatment of scoliosis, it is important both to slow down progression and to
      prevent the development of abnormal postural habits, which are part of a vicious
      circle even without progression. Secondary prevention is therefore needed in all
      patients. Passive observation limits the possibilities for prevention and
      contradicts the principle of early implementation of rehabilitation. Depending on
      the size of the angle of curvature, recommended treatments of scoliosis comprise
      observation, corset bracing, and surgery. Physiotherapy is often treated as an
      unconventional and ineffective treatment. Often, the biggest problem is
      transferring the resulting correction to automatic maintenance of a correct
      posture in the vertical position. The aim of this paper was to discuss the
      conservative treatment of scoliosis with regard to difficulties maintaining the
      correct alignment of the body parts in the vertical position that accompany
      scoliosis.

PMID- 22619096
TI  - Evaluation of the effectiveness of therapeutic massage in patients with neck
      pain.
AB  - BACKGROUND: Neck pain is one of the most common musculoskeletal ailments. The aim
      of this study was to evaluate the effectiveness and impact of therapeutic massage
      on the range of motion in patients with neck pain. MATERIAL AND METHODS: The
      study involved 60 patients aged 37-82 years (mean age: 62.8 +/- 9.86 years)
      treated for neck pain at the Rehabilitation Department of Zamosc University of
      Management and Administration. The patients were divided into two groups: one (30
      persons) received kinesiotherapy and physiotherapy, and the other group (30
      persons) additionally received therapeutic massage. The effectiveness of
      rehabilitation was assessed with a Saunders digital inclinometer, the Neck
      Disability Index (NDI) and a Visual Analogue Scale (VAS). RESULTS: Both groups
      did not differ significantly in terms of NDI and VAS scores at baseline (NDI: p =
      0.56, VAS: P = 0.231) and after rehabilitation (NDI: p = 0.203; VAS: P = 0.401).
      The NDI questionnaire and VAS revealed a significant pain reduction (p <0.001),
      and improved performance and function (p <0.001) after rehabilitation in both
      groups. Patients who had received massage demonstrated a statistically
      significant improvement in the range of flexion (p = 0.022), lateral bend to the
      right (p = 0.018), and lateral bend to the left (p = 0.003). CONCLUSIONS: 1.
      Therapeutic massage increases ranges of motion. 2. The effectiveness of
      therapeutic massage is comparable to the effectiveness of rehabilitation based
      only on physical therapy and kinesiotherapy.

PMID- 22619097
TI  - Accuracy of diagnoses in patients with spinal cord injury referred to hospital
      rehabilitation departments.
AB  - BACKGROUND: Establishing a comprehensive diagnosis, together with the
      implementation of evidence-based therapeutic methods, is a prerequisite for
      effective and safe rehabilitation. The purpose of the study was to evaluate the
      accuracy of referral diagnoses and identify the risk factors for diagnostic
      neglect in persons after spinal injury with neurological consequences (SINC)
      referred to rehabilitation departments in hospitals. MATERIAL AND METHODS:
      Referral diagnoses were compared with tentative diagnoses established on
      admission in 350 randomly chosen patients with SINC admitted to a rehabilitation
      department between 1998 and 2011. The patients were divided into Group A of those
      admitted in 1998-2004 and Group B of those admitted in 2006-11 (175 subjects
      each). The patterns of and risk factors for inaccurate and deficient referral
      diagnoses (IDRD) were analyzed. RESULTS: The rate of IDRD was 38.3% in Group A
      and 35.4% in Group B. The number of diagnoses where additional data were added
      after verification on admission was 111 in Group A and 129 in Group B. The most
      common deficiencies in referral diagnoses consisted in the failure to identify
      symptomatic urinary tract infections (49), heterotopic ossification (39), and
      pressure sores (32). The IDRD rate was significantly (p>0.05) higher in patients
      referred from hospitals, surgical departments, those with thoracic spine lesions,
      complete neurological deficits, and those with at least two co-morbidities or
      concomitant injuries. Median time between SINC and admission for rehabilitation
      was longer in subjects with accurate referral diagnoses (180 days) compared with
      the IDRD group (54 days). Age, gender and cause of SINC did not correlate with
      IDRD. CONCLUSIONS: Risk factors for IDRD in SINC patients include complete
      neurological deficit, short time elapsing from SINC, referral from a hospital,
      referral from a surgical department, thoracic spinal lesion, and multiple co
      morbidities.

PMID- 22619098
TI  - Biomechanical assessment of varus-valgus range of motion of normal elbow joint
      using prototype measuring device.
AB  - INTRODUCTION: Elbow joint stability is provided by the medial and lateral
      collateral ligaments, joint surface alignment, and the joint capsule. The
      contribution of the joint capsule is relatively minor and varies with the
      position of the joint. The normal range of forearm abduction and adduction in the
      elbow joint is estimated to be between 5 and 10 degrees . The aim of the paper
      was to determine precisely the physiological range of elbow joint motion in the
      frontal plane (laxity), which, apart from the knowledge gained, will provide a
      means to assess the effect of the surgical treatment of elbow joint contractures
      by comparing the stability of operated and healthy joints. MATERIAL AND METHODS:
      The measurements were carried out using UB-01, a prototype device produced by ANT
      Polska, in a group of 52 healthy volunteers. RESULTS: The mean valgus and varus
      deviation of the elbow joint was 11.2 degrees  (6.4 degrees  16.1 degrees ) and
      6.6 degrees  (3 degrees  10.7 degrees ), respectively. The mean degree of elbow
      joint laxity was 17.8 degrees  (10.6 degrees  26.5 degrees ). The difference in
      laxity between two opposite elbow joints in the same person was, on average, 1.2
      degrees  (0.1 degrees  3.8 degrees ). In healthy persons, the amplitude of
      deviation for both elbows is significantly smaller than 2 degrees . CONCLUSIONS:
      1. There are major differences in elbow joint laxity between individuals. 2.
      Nevertheless, laxity values of two elbow joints in the same individual are very
      similar. This observation allows for the healthy elbow to be treated as a
      reference while assessing the affected joint's stability in a patient following
      conventional surgery for elbow joint contracture.

PMID- 22619099
TI  - Intra- and interobserver repeatability of the assessment of anteroposterior
      curvatures of the spine using Saunders digital inclinometer.
AB  - INTRODUCTION: According to the requirements of Evidence Based Medicine, every
      research tool and method should be subjected to reliability evaluation. A variety
      of inclinometers are used for the assessment of sagittal plane spinal curvatures
      in clinical practice. The aim of the study was to evaluate the intra- and
      interobserver repeatability of measurements of the anterior-posterior spinal
      curvatures taken with Saunders digital inclinometer. MATERIAL AND METHODS: The
      study involved 30 healthy subjects (5 males, 25 females) aged 20 to 35 years. The
      anteroposterior curvatures of the spine were measured in all subjects using a
      Saunders digital inclinometer. In order to evaluate the intraobserver
      repeatability of measurements, the results obtained by one investigator were
      compared. To evaluate interobserver repeatability, the results obtained by three
      investigators were compared. Additionally, the levels of reliability and
      measurement error were determined. RESULTS: The measurements conducted by one
      investigator showed good repeatability for sacral slope, lumbar lordosis, and
      thoracic kyphosis, including the angle of proximal (Th1-Th6) and distal (Th6
      Th12) thoracic kyphosis (p>0.05). For measurements taken by three investigators,
      interobserver repeatability was achieved for thoracic kyphosis (p>0.05). The
      reliability of the measurements was good (Cronbach's alpha was 0.9> alpha >=0.8),
      and the measurement error was between 2.8 degrees -3.8 degrees . CONCLUSIONS: The
      assessment of anteroposterior curvatures of the spine by one investigator
      provided good repeatability and reliability of measurements. Measurements
      performed by more than one investigator displayed partial repeatability. The
      value of the observational error should be taken into account in the
      interpretation of results of measurements performed with the Saunders
      inclinometer. The assessment of anteroposterior curvatures of the spine should be
      preceded by a verification of measurement reliability.

PMID- 22619100
TI  - Avascular necrosis of the femoral head in sickle cell disease patients.
AB  - BACKGROUND: Avascular necrosis of the femoral head (ANFH) has been described as a
      frequent outcome in patients with sickle cell disease (SCD). The objective of the
      current report is to present the prevalence of ANFH in patients under the age of
      21 suffering from SCD as well as discuss some possible associated risk factors.
      MATERIAL AND METHOD: A cross-sectional study was carried out in a group of 100
      patients. Clinical, demographic variables and risk factors were investigated.
      Seventy-two patients had their data completely analyzed. Eight patients were
      found to be affected and comprise the study group while the other 64 patients
      comprised the comparison group. RESULTS: The prevalence of ANFH was 8 out of 72
      (11.1%). Age (p=0.042), weight (p=0.04) and hemoglobin levels (0.048) were
      associated with ANFH. Correlations with time from diagnosis (p=0.14), ulcers
      (p=0.013), ferritin levels (p=0.07) and a family history of thrombosis were near
      significant. CONCLUSIONS: The attention of physicians treating SCD patients must
      also be drawn to the possibility of ANFH in order to prevent or avoid this
      disastrous complication, especially in younger patients presenting with frequent
      hemolytic crises.

PMID- 22619101
TI  - A comparison of effectiveness of fascial relaxation and classic model of patients
      rehabilitation after hip joint endoprosthetics.
AB  - BACKGROUND: Degenerative joint disease usually leads to functional failure and
      pain in the affected parts of the musculoskeletal system. The aim of this study
      was to evaluate the effectiveness of fascial relaxation for tense muscles in the
      affected hip joint by comparing this method and classic physiotherapeutic
      rehabilitation in patients after hip arthroplasty with regard to the range of
      motion, presence of pain and quality of life. MATERIAL AND METHODS: The study
      involved 35 females qualified for hip arthroplasty. A control group consisted of
      10 patients aged 47 to 77 years who received classic kinesiotherapy, including
      antithrombotic prophylaxis and isometric muscle exercises for the operated lower
      limb followed by active exercises for supported flexion in the hip and knee
      joints, active decompression exercises, assuming the upright position, and gait
      training. The experimental group consisted of 25 women aged 45 to 75 years who,
      along with conventional therapeutic exercises, were treated by fascial relaxation
      of the affected hip joint. The arthroplasty procedure was carried out from a
      posterior approach in all patients, in accordance with the technique recommended
      by Swanson. RESULTS: The results indicate that the group of patients who
      additionally received fascial relaxation demonstrated a significantly increased
      range of motion in the operated hip joint. The experimental group also reported
      considerable pain reduction and improved daily activity in comparison to the
      control group. CONCLUSIONS: The techniques of fascial relaxation significantly
      reduced recovery time and liminated muscle tensing in the operated hip joint,
      thus contributing to improving the range of motion.

PMID- 22619102
TI  - Inverted cup prosthesis to treat recurrent hip dislocation in frail elderly
      patients.
AB  - Recurrent hip dislocation has become an increasing problem in patients who had
      multiple component revision in total hip arthroplasty. These are often frail
      elderly patients with loss of constraining soft tissue envelope around the hip
      and an excessive weakness of the abductor mechanism. We present a simple
      technique for open reduction of a dislocated hip using a custom-made fully
      constrained construct with potential for preserving the well fixed femoral
      implant and parts of the acetabular component. The custom-made constrained
      construct consists of the application of an inverted cup over the femoral neck or
      head, the cup being fixed to the acetabular insert with screws. Three frail
      elderly patients have been successfully treated. One specific case is described
      in detail. In frail elderly patients who may have undergone several revision
      surgeries, it is important to preserve components of the total hip replacement
      when possible. The proposed technique may be an alternative solution for these
      patients.

PMID- 22619103
TI  - Isolated osteochondroma of the femoral neck presenting as hip and leg pain. A
      case study.
AB  - Osteochondromas, or exostoses, are overwhelmingly found as isolated lesions
      although they can be present within the context of multiple hereditary exostosis.
      Increased exostotic load associated with multiple hereditary exostosis can lead
      to limb-length discrepancy, increased femoral anteversion, valgus angulation, and
      acetabular dysplasia. Solitary osteochondromas have been linked with bursal
      inflammation and pain, compression on neurovascular structures, and malignant
      degeneration, groin and lower extremity pain. Isolated exostosis involving the
      femoral neck is a rare entity which is often diagnosed late when the patient is
      being investigated for other problems. We present a young female with a history
      of hip pain for 3 years with restriction of movements around the hip joint and
      radicular pain which turned out to be a solitary osteochondroma of the femoral
      neck. Surgical excision relieved the symptoms.

PMID- 22619104
TI  - Recurrence of tuberculosis after hip replacement 58 years after primary
      infection.
AB  - The paper presents the case of a 73-year-old patient with a history of
      tuberculosis of the hip in childhood who received an Exeter total hip prosthesis.
      Tuberculosis recurred 58 years after primary infection and 9 years after THA. The
      authors analyzed the available literature, which described only a few case
      reports, because Mycobacterium tuberculosis infections of a joint implant after
      THA are extremely rare. They are frequently the result of local reactivation of
      the pathogen or, less commonly, an overlooked diagnosis of tuberculosis at the
      time of endoprosthesis implantation. Proper diagnostic work-up of infection is
      particularly difficult because synovial fluid cultures are usually negative. In
      addition, a coexisting Staphylococcus aureus infection may obscure the clinical
      presentation. In post-THA patients, complete anti-TB treatment is recommended.
      Particular caution should be observed in patients from regions with high TB
      morbidity or with a history of pulmonary and operated joint tuberculosis.

PMID- 22619105
TI  - Automated identification of binding sites for phosphorylated ligands in protein
      structures.
AB  - Phosphorylation is a crucial step in many cellular processes, ranging from
      metabolic reactions involved in energy transformation to signaling cascades. In
      many instances, protein domains specifically recognize the phosphogroup.
      Knowledge of the binding site provides insights into the interaction, and it can
      also be exploited for therapeutic purposes. Previous studies have shown that
      proteins interacting with phosphogroups are highly heterogeneous, and no single
      property can be used to reliably identify the binding site. Here we present an
      energy-based computational procedure that exploits the protein three-dimensional
      structure to identify binding sites involved in the recognition of phosphogroups.
      The procedure is validated on three datasets containing more than 200 proteins
      binding to ATP, phosphopeptides, and phosphosugars. A comparison against other
      three generic binding site identification approaches shows higher accuracy values
      for our method, with a correct identification rate in the 80-90% range for the
      top three predicted sites. Addition of conservation information further improves
      the performance. The method presented here can be used as a first step in
      functional annotation or to guide mutagenesis experiments and further studies
      such as molecular docking.

PMID- 22619106
TI  - High percentage of cancer outpatients are at nutritional risk.

PMID- 22619107
TI  - Sustained virological response prevents the development of insulin resistance in
      patients with chronic hepatitis C.
AB  - Hepatitis C virus (HCV) infection is associated with insulin resistance (IR),
      which is a condition known to influence the progression of liver fibrosis and the
      response to pegylated interferon (PEG-IFN)/ribavirin (RBV) therapy. We aimed to
      assess whether a sustained virological response (SVR) after antiviral therapy
      prevents the development of IR in the long term. Members of the Milan Safety
      Tolerability study cohort, who received PEG-IFNalpha2a/RBV or PEG-IFNalpha2b/RBV,
      underwent a homeostasis model assessment (HOMA) at the baseline and 24 months
      after treatment completion. For all patients (n = 431), a liver biopsy sample was
      scored for grading, staging (Ishak), and steatosis. At the baseline, IR (HOMA
      value > 2) was detected in 48 patients (12%), and it was associated with body
      weight (P = 0.03), an HCV load < 0.6 * 10(6) IU/L (P = 0.006), fibrosis staging
      >= 4 (P = 0.01), and moderate to severe steatosis (P = 0.03). IR did not
      influence the rates of end-of-treatment response (75% versus 69%, P = 0.4), SVR
      (63% versus 60%, P = 0.8), or relapse (19% versus 24%, P = 0.5). After treatment,
      IR developed in 49 of the 384 nondiabetic patients (14%). Although the mean
      baseline and posttreatment HOMA values were similar in SVR patients (1.11 +/- 0.8
      versus 1.18 +/- 1.1, P = 0.25), patients experiencing treatment failure showed a
      significant increase in the mean HOMA value at the follow-up visit (1.20 +/- 0.85
      versus 1.49 +/- 1.3, P = 0.007), and there was an increased rate of de novo IR in
      non-SVR patients versus SVR patients (17% versus 7%, P = 0.007). According to a
      logistic regression analysis, treatment failure (odds ratio = 2.81, 95%
      confidence interval = 1.39-5.67, P = 0.004) and a 10% body mass index increase
      (odds ratio = 6.42, 95% confidence interval = 1.69-24.3, P = 0.006) were
      significantly associated with the development of de novo IR. CONCLUSION: In
      nondiabetic patients with chronic HCV, the achievement of SVR with PEG-IFN and
      RBV prevents the development of de novo IR.

PMID- 22619108
TI  - The effect of humic and glutamic acids in nutrient solution on the N metabolism
      in lettuce.
AB  - BACKGROUND: This paper reports for the first time the influence of partially
      replacing the nitrogen (N) source of a nutrient solution with amino acids and
      humic acid on the physiological and antioxidant activities and N metabolism in
      lettuce. A hydroponic experiment was designed to replace 25 and 50% of the N in
      nutrient solutions (NSs) with glutamic acid (GA) and humic acid (HA) and evaluate
      the effects on growth, nitrate (NO(3)) assimilation, protein content, nitrate
      reductase (NR) activity and antioxidant changes in lettuce. RESULTS: The results
      showed that, when a portion of the N was replaced with GA and HA, the fresh and
      dry weights of lettuce shoots did not change significantly compared with the full
      NO(3) treatment. The titratable acidity was not affected by adding HA and/or GA
      to the NS. The nitrite concentration and NR activity decreased with reductions in
      the N concentration of the NS and improved with the addition of GA and HA. GA
      enhanced the NO(3) uptake and protein content more than HA. Changes in the
      superoxide dismutase (SOD) and peroxidase (POD) activities and malondialdehyde
      content were inconclusive: SOD and POD activities decreased with decreasing N
      content of the NS, and HA addition improved the SOD and POD activities.
      CONCLUSION: When HA and GA were substituted for NO(3) in an NS, the acids
      effectively adjusted the N metabolism and growth in lettuce and decreased the N
      consumption of the NS.

PMID- 22619109
TI  - On the quantification of intertest variability in ecotoxicity data with
      application to species sensitivity distributions.
AB  - Ecotoxicological hazard assessment relies on species effect data to estimate
      quantities such as the predicted no-effect concentration. While there is a
      concerted effort to quantify uncertainty in risk assessments, the uncertainty due
      to intertest variability in species effect measurements is an overlooked
      component. The European Union Registration, Evaluation, Authorisation, and
      Restriction of Chemicals (REACH) guidance document suggests that multiple
      toxicity records for a given chemical-species combination should be aggregated by
      the geometric mean. Ignoring this issue or applying unjustified so-called
      harmonization methods weakens the defensibility of uncertainty quantification and
      interpretation about properties of ecological models, for example, the predicted
      no-effect concentration. In the present study, the authors propose a simple and
      broadly theoretically justifiable model to quantify intertest variability and
      analyze it using Bayesian methods. The value of data in ecotoxicity databases is
      maximized by using (interval-)censored data. An exploratory analysis is provided
      to support the model. The authors conclude, based on a large ecotoxicity database
      of acute effects to aquatic species, that the standard deviation of intertest
      variability is approximately a factor (or fold-difference) of 3. The consequences
      for decision makers of (not) adjusting for intertest variability are
      demonstrated.

PMID- 22619110
TI  - Identification of a novel partner gene, TPR, fused to FGFR1 in 8p11
      myeloproliferative syndrome.
AB  - The 8p11 myeloproliferative syndrome (EMS) is an aggressive neoplasm caused by
      the fusion of various partner genes to fibroblast growth factor receptor 1
      (FGFR1). Various FGFR1 fusions are associated with subtly distinct disease
      phenotypes. Here, we report a new translocation at the FGFR1 locus in a patient
      who carried t(1;8)(q25;p11.2) and presented with myeloproliferative neoplasm-like
      symptoms. The patient was characterized by myeloid hyperplasia of bone marrow,
      markedly elevated numbers of monocytes, and normal to mildly elevated
      eosinophils. Initial fluorescent in situ hybridization analysis confirmed that
      FGFR1 in this patient was disrupted. Subsequent analysis led to the
      identification of a novel translocation, in which exon 23 of the translocated
      promoter region (TPR) gene at chromosome band 1q25 was fused to exon 13 of FGFR1
      (RefSeq NM_0231102.2). The TPR portion of the fusion protein contains putative
      functional motifs including an N-terminal TprMet domain, nuclear pore complexes
      associating domain, and multiple coiled-coil domains. It is likely that one or
      more of the motifs from TPR contribute to dimerization, resulting in constitutive
      activation of the FGFR1 kinase domain. Our results further support a critical
      role of FGFR1 in the pathogenesis of EMS and may lead to more accurate diagnosis
      and potential targeted therapy.

PMID- 22619111
TI  - Titania-polymeric powder coatings with nano-topography support enhanced human
      mesenchymal cell responses.
AB  - Titanium implant osseointegration is dependent on the cellular response to
      surface modifications and coatings. Titania-enriched nanocomposite polymeric
      resin coatings were prepared through the application of advanced ultrafine powder
      coating technology. Their surfaces were readily modified to create nano-rough
      (<100 nm) surface nano-topographies that supported human embryonic palatal
      mesenchymal cell responses. Energy dispersive x-ray spectroscopy confirmed
      continuous and homogenous coatings with a similar composition and even
      distribution of titanium. Scanning electron microscopy (SEM) showed complex micro
      topographies, and atomic force microscopy revealed intricate nanofeatures and
      surface roughness. Cell counts, mitochondrial enzyme activity reduction of yellow
      3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) to dark
      purple, SEM, and inverted fluorescence microscopy showed a marked increase in
      cell attachment, spreading, proliferation, and metabolic activity on the
      nanostructured surfaces. Reverse Transcription- Polymerase Chain Reaction (RT
      PCR) analysis showed that type I collagen and Runx2 expression were induced, and
      Alizarin red staining showed that mineral deposits were abundant in the cell
      cultures grown on nanosurfaces. This enhancement in human mesenchymal cell
      attachment, growth, and osteogenesis were attributed to the nanosized surface
      topographies, roughness, and moderate wetting characteristics of the coatings.
      Their dimensional similarity to naturally occurring matrix proteins and crystals,
      coupled with their increased surface area for protein adsorption, may have
      facilitated the response. Therefore, this application of ultrafine powder coating
      technology affords highly biocompatible surfaces that can be readily modified to
      accentuate the cellular response.

PMID- 22619112
TI  - Proliferating primary hepatocytes from the pUR288 lacZ plasmid mouse are valuable
      tools for genotoxicity assessment in vitro.
AB  - Safety assessments of substances with regard to genotoxicity are generally based
      on a combination of in vitro and in vivo tests. These tests are performed
      according to a (tiered) test strategy whereby a positive result in vitro usually
      triggers further testing in vivo. A low specificity and high frequency of
      irrelevant positive results associated with most in vitro mammalian cell
      genotoxicity assays necessitates the design and validation of suitable
      alternatives. As such, we examined the feasibility of culturing primary
      hepatocytes from the pUR288 lacZ reporter mouse, and moreover, using established
      cultures to reliably assess genotoxic activity in vitro. Initial studies
      characterizing the metabolic capacity of proliferating lacZ primary hepatocytes
      indicated that these cells retained at least some activities important for
      xenobiotic metabolism: cytochrome P450 1A1 enzyme activities were markedly
      increased in the hepatocytes after exposure to benzo[a]pyrene, and also UDP
      glucuronosyl transferase and glutathione-S-transferase activities, both Phase II
      enzymes, were detected. Increasing levels of phosphorylated p53 at residue serine
      389 after ultraviolet treatment indicated a properly functioning p53, one of the
      criteria for an effective new test system. Four genotoxic substances with
      different mechanisms of genotoxicity, i.e., benzo[a]pyrene, bleomycin, etoposide,
      and cyclophosphamide, were tested in the lacZ rescue assay. For etoposide and
      cyclophosphamide, the induction of mutant colonies was rather low. Exposure to
      benzo[a]pyrene and bleomycin, however, yielded a clear concentration-dependent
      induction of the lacZ mutant frequency. Based on our preliminary observations,
      proliferating lacZ primary hepatocytes are a promising new tool for the
      assessment of genotoxic hazard.

PMID- 22619114
TI  - Validation of new psychosocial factors questionnaires: a Colombian national
      study.
AB  - BACKGROUND: The study of workers' health problems possibly associated with
      stressful conditions requires valid and reliable tools for monitoring risk
      factors. The present study validates two questionnaires to assess psychosocial
      risk factors for stress-related illnesses within a sample of Colombian workers.
      METHODS: The validation process was based on a representative sample survey of
      2,360 Colombian employees, aged 18-70 years. Worker response rate was 90%; 46% of
      the responders were women. Internal consistency was calculated, construct
      validity was tested with factor analysis and concurrent validity was tested with
      Spearman correlations. RESULTS: The questionnaires demonstrated adequate
      reliability (0.88-0.95). Factor analysis confirmed the dimensions proposed in the
      measurement model. Concurrent validity resulted in significant correlations with
      stress and health symptoms. CONCLUSIONS: "Work and Non-work Psychosocial Factors
      Questionnaires" were found to be valid and reliable for the assessment of
      workers' psychosocial factors, and they provide information for research and
      intervention.

PMID- 22619113
TI  - The Hsp90 inhibitor NVP-AUY922-AG inhibits NF-kappaB signaling, overcomes
      microenvironmental cytoprotection and is highly synergistic with fludarabine in
      primary CLL cells.
AB  - Heat shock protein 90 (Hsp90) is a molecular chaperone required for the stability
      and function of multiple over-expressed signaling proteins that promote growth
      and survival in cancer cells. Chronic lymphocytic leukaemia (CLL) is
      characterized by increased expression of several Hsp90 client proteins making it
      a potentially susceptible to Hsp90 inhibition. In this study we showed that the
      novel Hsp90 inhibitor NVP-AUY922-AG was cytotoxic to primary CLL cells in vitro
      (LD50=0.18MUM+/-0.20). Importantly, its toxicity was preserved under
      cytoprotective co-culture conditions that rendered fludarabine ineffective. At
      the molecular level, NVP-AUY922-AG depleted the expression of multiple Hsp90
      client proteins including Akt and activators of NF- kappaB, IKKalpha and IKKbeta.
      Consistent with this inhibition profile, NVP-AUY922-AG resulted in decreased
      transcription of the NF-B target genes MCL1, CFLAR, BIRC5. In contrast,
      fludarabine significantly induced the transcription of MCL1 and BIRC5. Given the
      anti-apoptotic nature of these genes and the role they play in fludarabine
      resistance, we considered that the combination of NVP-AUY922-AG with fludarabine
      might resensitize CLL cells to the effects of fludarabine. In keeping with this
      hypothesis, the combination of NVP-AUY922-AG and fludarabine was highly
      synergistic (mean CI=0.110.06) and this synergy was enhanced in co-culture (mean
      CI=0.06+/-0.08). Furthermore, the combination maintained the decrease in MCL1,
      CFLAR and BIRC5 transcription suggesting that the ability of NVP-AUY922-AG to
      modulate expression of these genes may contribute to the efficacy of this drug
      under cytoprotective co-culture conditions and for its remarkable synergy with
      fludarabine. Taken together these findings indicate that Hsp90 inhibition is an
      attractive therapeutic strategy in CLL.

PMID- 22619115
TI  - Prediction of the properties and thermodynamics of formation for energetic
      nitrogen-rich salts composed of triaminoguanidinium cation and 5
      nitroiminotetrazolate-based anions.
AB  - Density functional theory and volume-based thermodynamics calculations were
      performed to study the effects of different substituents and linkages on the
      densities, heats of formation (HOFs), energetic properties, and thermodynamics of
      formation for a series of energetic nitrogen-rich salts composed of
      triaminoguanidinium cation and 5-nitroiminotetrazolate anions. The results show
      that the -NO(2), -NF(2), or -N(3) group is an effective substituent for
      increasing the densities of the 5-nitroiminotetrazolate salts, whereas the
      effects of the bridge groups on the density are coupled with those of the
      substituents. The substitution of the group -NH(2), -NO(2), -NF(2), -N(3), or the
      nitrogen bridge is helpful for increasing the HOFs of the salts. The calculated
      energetic properties indicate that the -NO(2), -NF(2), -N(3), or -N=N- group is
      an effective structural unit for improving the detonation performance for salts.
      The thermodynamics of formation of the salts show that all the salts may be
      synthesized easily by the proposed reactions. The structure-property
      relationships provide basic information for the molecular design of novel high
      energy salts.

PMID- 22619116
TI  - Development of a molecular biomarker for detecting intersex after exposure of
      male medaka fish to synthetic estrogen.
AB  - Although intersex of fish species has been widely reported in aquatic
      environments, there is no appropriate biomarker of the effects to assess the
      occurrence of intersex. In the present study, mRNA expression profiles of 14
      genes, which are either involved in ovary development and maintenance or have
      relatively high mRNA transcription levels in ovarian gene expression profiles in
      fish species, were comprehensively evaluated in male Japanese medaka (Oryzias
      latipes) exposed to 17alpha-ethynylestradiol (EE2) to investigate their utility
      as indicators of the severity index of intersex. Of these 14 genes, mRNA
      expression of a novel gene, termed ovary structure protein 1 (OSP1) in the
      present study, showed female-like expression pattern with the highest
      transcription levels, and displayed the most significantly positive correlation
      with the severity index of intersex (r(2) =0.8215, p<0.0001). The full-length
      mRNA sequence of OSP1 is 802 bp, with an open reading frame (ORF) of 642 bp that
      encodes a 214-amino acid peptide. Reverse transcription polymerase chain reaction
      and in situ hybridization revealed that OSP1 was expressed exclusively in the
      ovaries, specifically in the oogonia and primary oocytes in ovaries and in testis
      with intersex. These results suggest that the analysis of mRNA expression of OSP1
      can be used to indicate intersex in male medaka.

PMID- 22619118
TI  - Prevalence of CGG expansions of the FMR1 gene in a US population-based sample.
AB  - The primary goal of this study was to calculate the prevalence of the premutation
      of the FMR1 gene and of the "gray zone" using a population-based sample of older
      adults in Wisconsin (n = 6,747 samples screened). Compared with past research,
      prevalence was relatively high (1 in 151 females and 1 in 468 males for the
      premutation and 1 in 35 females and 1 in 42 males for the gray zone as defined by
      45-54 CGG repeats). A secondary study goal was to describe characteristics of
      individuals found to have the premutation (n = 30, 7 males and 23 females). We
      found that premutation carriers had a significantly higher rate of divorce than
      controls, as well as higher rates of symptoms that might be indicative of fragile
      X-associated tremor ataxia syndrome (FXTAS; numbness, dizziness/faintness) and
      fragile X primary ovarian insufficiency (FXPOI; age at last menstrual period).
      Although not statistically significant, premutation carriers were twice as likely
      to have a child with disability.

PMID- 22619122
TI  - Bridging the gap: cytopathology at the threshold of personalized medicine.

PMID- 22619121
TI  - A chemical screen identifies the chemotherapeutic drug topotecan as a specific
      inhibitor of the B-MYB/MYCN axis in neuroblastoma.
AB  - The transcription factor MycN is the prototypical neuroblastoma oncogene and a
      potential therapeutic target. However, its strong expression caused by gene
      amplification in about 30% of neuroblastoma patients is a considerable obstacle
      to the development of therapeutic approaches aiming at eliminating its
      tumourigenic activity. We have previously reported that B-Myb is essentially
      required for transcription of the MYCN amplicon and have also shown that B-MYB
      and MYCN are engaged in a feed forward loop promoting the survival/proliferation
      of neuroblastoma cells. We postulated that pharmacological strategies breaking
      the B-MYB/MYCN axis should result in clinically desirable effects. Thus, we
      implemented a high throughput chemical screen, using a curated library of ~1500
      compounds from the National Cancer Institute, whose endpoint was the
      identification of small molecules that inhibited B-Myb. At the end of the
      screening, we found that the compounds pinafide, ellipticine and camptothecin
      inhibited B-Myb transcriptional activity in luciferase assays. One of the
      compounds, the topoisomerase-1 inhibitor camptothecin, is of considerable
      clinical interest since its derivatives topotecan and irinotecan are currently
      used as first and second line treatment agents for various types of cancer,
      including neuroblastoma. We found that neuroblastoma cells with amplification of
      MYCN are more sensitive than MYCN negative cells to camptothecin and topotecan
      killing. Campothecin and topotecan caused selective down-regulation of B-Myb and
      MycN expression in neuroblastoma cells. Notably, forced overexpression of B-Myb
      could antagonize the killing effect of topotecan and camptothecin, demonstrating
      that the transcription factor is a key target of the drugs. These results suggest
      that camptothecin and its analogues should be more effective in patients whose
      tumours feature amplification of MYCN and/or overexpression of B-MYB.

PMID- 22619124
TI  - Telecytology and its evolving role in cytopathology.
AB  - The advancement of telecommunication technology in the area of digital transfer
      of images form distant site has resulted in exploration of this technology in the
      area of cytopathology. Telecytology facilitates the electronic transmission of
      microscopic images using static, dynamic, and whole slide imaging systems. Recent
      articles have generated an interest in the use of this technology for immediate
      assessment of fine-needle aspirations. Telecytology has potential for use in
      second opinion, quality assurance, slide archiving, proficiency testing, and
      distance-based education. This review discusses the current and potential
      applications of telecytology in cytopathology practice and its limitation and
      advantages.

PMID- 22619123
TI  - CD147 immunohistochemistry discriminates between reactive mesothelial cells and
      malignant mesothelioma.
AB  - Malignant mesothelioma (MM) is a rare form of cancer. Its histopathological
      diagnosis is very difficult, as it exhibits a number of different appearances
      that can be misinterpreted as metastatic invasion or atypical hyperplasia. Thus,
      there is an urgent need to identify adequate markers to distinguish between
      benign and malignant cells, allowing the implementation of appropriate therapies
      and, possibly, specific directed therapies. MM, like other tumors, show an
      increase in glucose uptake, due to high rates of glycolysis, inducing an
      intracellular overload of acids. In this context, monocarboxylate transporters
      (MCTs) emerge as important players, by mediating the transmembranar co-transport
      of lactate with a proton, thereby, regulating pH and allowing continuous
      glycolysis. Importantly, proper MCT expression and activity depend on its co
      expression with a chaperone, CD147, which is associated with poor prognosis in
      cancer. Twenty-two samples including reactive mesothelial cells, MM, and atypical
      mesothelial hyperplasias were evaluated for immunoexpression of MCT1, MCT4, and
      CD147. Expression of these proteins was compared with GLUT1 as a new promising
      marker for MM. Although MCT isoforms were not differentially expressed in the two
      types of cytological specimens, CD147, as GLUT1, was almost exclusively expressed
      in MM. Both MCT1 and MCT4 are not able to discriminate between mesothelial
      reactive cells and mesothelial malignant cells, while CD147 was able to
      distinguish these two proliferations. If confirmed, besides being a good marker
      for identification of MM, CD147 may also be a target for therapeutical strategies
      in this rare type of tumor.

PMID- 22619125
TI  - Molecular testing in malignant melanoma.
AB  - Molecular testing of cancers to determine therapeutic eligibility is now standard
      of care and has changed the practice of pathology. Recent advances in the
      treatment of metastatic melanoma with BRAF and KIT inhibitors have increased the
      demand for molecular testing in melanoma. Furthermore, rapid progress is being
      made in determining potential new targets, mechanisms of resistance, and
      developing additional rationally designed therapies. The likely consequence will
      be a significant expansion of molecular testing for melanoma to include an array
      of multiple signaling intermediates. Currently, routine testing is mostly limited
      to BRAF and KIT. Mutations in these genes generally occur in a distinct group of
      melanoma subsets though, and with the numerous techniques available for mutation
      analysis, decisions about testing can be complex. The purpose of this review is
      to provide an overview of clinically relevant mutations which currently guide
      systemic therapy in Stage IV melanoma, how these molecular events vary with
      melanoma subtype and primary site of origin, and practical recommendations for
      testing.

PMID- 22619126
TI  - The role of cytology specimens in molecular testing of solid tumors: techniques,
      limitations, and opportunities.
AB  - Numerous studies have demonstrated the suitability of cytology specimens for
      molecular analysis. When combined with the ability to acquire tissue in a
      minimally invasive manner, testing on cytology specimens is an especially
      attractive method for further refining diagnosis, determining prognosis, and
      predicting likely response to therapy as well as monitoring disease. As the
      demand for testing of small specimens increases, the burden of determining
      whether a specimen should be referred for testing will increasingly be placed on
      the pathologist. Although molecular laboratories that perform this testing will
      also evaluate the suitability of the specimen, familiarity with the criteria for
      suitability, which includes an understanding of the limitations of the assay
      methodology, will assist in determining which specimens are appropriate for
      referral. Selection of specimen(s) for testing should be paired with knowledge of
      the testing methodology used and its limitations, as well as the tumor enrichment
      capabilities of the laboratory. In addition to an expanding need to participate
      in the referral of specimens for testing, the cytopathologist will increasingly
      serve as a critical link in the communication between molecular laboratory and
      clinical team.

PMID- 22619127
TI  - The diagnostic and research applications of flow cytometry in cytopathology.
AB  - Flow cytometry (FCM) is an established ancillary technique applied to the
      diagnosis of hematological malignancies and for measurement of DNA content. In
      recent years, the number of fluorochrome-conjugated antibodies available for
      immunofluorescence and FCM has greatly increased, making it possible to evaluate
      this technique in other diagnostic contexts, as well as to study a range of
      biological processes. Serous effusions are optimal for studies using FCM as they
      consist of viable cells in suspension. Molecules that have been studied for their
      expression and clinical role in effusions in recent years participate in central
      cellular functions, including adhesion, proliferation, cellular metabolism, and
      apoptosis, as well as intracellular signaling. FCM can further be applied to
      quantitative analysis of molecules related to chemotherapy response, which,
      together with apoptosis, may represent an important tool for evaluating treatment
      response and prognosis in advanced and/or recurrent cancer. As targeted therapy
      assumes an ever-growing role in the treatment of metastatic cancer, the ability
      to study living cells in effusions or fine-needle aspirates is becoming more
      important. This article reviews the currently available data in this area of
      cytopathology.

PMID- 22619128
TI  - Beyond cytomorphology: expanding the diagnostic potential for biliary cytology.
AB  - Malignancy of the extrahepatic biliary tract is a difficult and crucial
      diagnosis, both clinically and pathologically. Cytologic evaluation of brushings
      obtained endoscopically from the biliary tree is currently the standard of care
      in most institutions. However, bile duct brushing cytology has been plagued by
      low sensitivity and interpretative difficulties in differentiating reactive from
      malignant cytology. This review outlines both the difficulties presented by
      cytomorphology and the potential of new diagnostic techniques that promise to
      increase sensitivity without sacrificing the high specificity of cytomorphology.

PMID- 22619129
TI  - Molecular genetic characterization of lymphoma: application to cytology
      diagnosis.
AB  - Mature B- and T-cell lymphomas are increasingly being associated with specific
      genetic alterations; characterization of these changes can sometimes be crucial
      to both diagnosis and prognosis. Molecular testing encompasses fluorescence in
      situ hybridization (FISH) and polymerase chain reaction (PCR)-based assays, as
      well as classical cytogenetics. FISH and PCR-based assays can be performed on
      cytology material without the need for advanced planning for testing with fresh
      tissue. As many lymphoproliferations are amenable to fine needle aspiration
      diagnosis, it is important for the cytopathologist to be aware of what testing is
      feasible in these (sometimes limited) specimens. Here, we review pertinent
      genetic changes in mature B- and T-cell lymphomas with a focus on those that may
      be encountered more commonly in cytology specimens.

PMID- 22619130
TI  - Respiratory cytology in the era of molecular diagnostics: a review.
AB  - Carcinoma of the lungs remains one of the primary causes of cancer mortality in
      the United States and represents a significant diagnostic challenge. Current
      diagnostic protocols depend substantially on cytology as an initial diagnostic
      modality. Pulmonary cytology can be diagnostically challenging with false
      positive and false negative diagnoses being relatively frequent. False positive
      diagnoses remain a significant problem for the cytologist with benign conditions
      including reactive atypia of type II pneumocytes, reactive bronchial respiratory
      epithelium, basal cell hyperplasia, and reactive metaplastic squamous cells being
      potentially misinterpreted as carcinoma. False negative diagnoses also occur
      usually attributable to sampling. Traditionally, cytopathologists were expected
      to recognize carcinoma when present and subdivide it into small cell or nonsmall
      cell varieties. With the advent of targeted therapy, expectations now include
      separation of adenocarcinoma from squamous cell carcinoma. Additionally,
      molecular testing for EGFR mutations and ALK rearrangements is now required as an
      accompaniment to morphologic diagnosis. This review summarizes the morphologic
      appearances of the common and diagnostically important carcinomas of the lung and
      discusses diagnostic pitfalls responsible for false positive and false negative
      diagnoses. Molecular testing for selection of targeted therapy is also reviewed.

PMID- 22619131
TI  - Toxic thresholds of cadmium and lead to oceanic phytoplankton: cell size and
      ocean basin-dependent effects.
AB  - Thresholds of cadmium (Cd) and lead (Pb) toxic to oceanic phytoplankton were
      examined in natural communities from the Mediterranean and Black Seas and the
      North East Atlantic Ocean. At concentrations of added Cd and Pb greater than 0.11
      ug L(-1) , cell abundances and growth rates decreased with increasing addition of
      Cd and Pb, for all phytoplankton populations. The lethal concentrations at which
      populations decreased by half (LC50s), ranged from 0.23 to 498.7 ug L(-1) Cd for
      Atlantic Prochlorococcus and Black Sea picoeukaryotes, respectively, and from 20
      to 465.2 ug L(-1) Pb for Mediterranean Synechococcus and Black Sea nanoplankton,
      respectively. These lethal concentrations were significantly lower than those
      previously reported for phytoplankton cultures. The LC50s were strongly related
      to population cell size, increasing as cell size increased, indicating that
      oceanic picocyanobacteria Prochlorococcus and Synechococcus populations were the
      most sensitive, and the largest phytoplankton cells the most resistant. Based on
      this relationship, differences in sensitivity to Cd across systems were detected,
      with Black Sea phytoplankton communities being more resistant (up to 100 times)
      than similar sized phytoplankton of the Mediterranean Sea and Atlantic Ocean.

PMID- 22619132
TI  - Prevalence and heritability of skin picking in an adult community sample: a twin
      study.
AB  - Skin-picking disorder (SPD) is a disabling psychiatric condition that can lead to
      skin damage and other medical complications. Epidemiological data is scarce and
      its causes are unknown. The present study examined the prevalence and
      heritability of skin-picking symptoms in a large sample of twins. A total of
      2,518 twins completed a valid and reliable self-report measure of skin-picking
      behavior. The prevalence of clinically significant skin picking was established
      using empirically derived cut-offs. Twin modeling methods were employed to
      decompose the variance in the liability to skin picking into additive genetic and
      shared and non-shared environmental factors. A total of 1.2% of twins scored
      above the cut-off, indicative of clinically significant skin picking. All these
      participants were women. Univariate model-fitting analyses (female twins only, N
      = 2,191) showed that genetic factors accounted for approximately 40% (95% CI 19
      58%) of the variance in skin picking, with non-shared environmental factors and
      measurement error accounting for the remaining variance (60% [95% CI 42-81%]).
      Shared environmental factors were negligible. It is concluded that pathological
      skin picking is relatively prevalent problem, particularly among women, and that
      it tends to run in families primarily due to genetic factors. Non-shared
      environmental factors are also likely to play an important role in its etiology.

PMID- 22619133
TI  - Syntheses and highly enantioselective fluorescent recognition of alpha
      aminocarboxylic acid anions using chiral oxacalix[2]arene[2]bisbinaphthes.
AB  - The triazine-based bisbinaphthyl crown ethers oxacalix[2]arene[2]bisbinaphthes R
      1, R-2, R-3 and S-1, S-2, S-3 were synthesized. The interactions of these
      compounds with various alpha-aminocarboxylic acid anions were studied. The crown
      ethers were found to carry out highly enantioselective fluorescent recognition of
      alpha-aminocarboxylic acid anions. It is observed that within a certain
      concentration range, one enantiomer of the chiral alpha-aminocarboxylic acid
      anions can increase the fluorescence intensity of the crown ethers by fivefold to
      sixfold, whereas the other enantiomer scarcely enhances the fluorescence. Such
      unusually high enantioselective responses make these crown ethers very attractive
      as fluorescent sensors in determining the enantiomeric composition of alpha
      aminocarboxylic acid anions.

PMID- 22619135
TI  - Vesicoureteric reflux (VUR) in children: where are we now?
AB  - In 1960 Hodson and Edwards published their landmark paper about the association
      between chronic pyelonefritis and vesicoureteric reflux (VUR). Since then,  the
      approach for VUR became more important (1). In the last 30 years there have been
      multiple publications on vesicoureteric reflux (VUR) and discussions at Pediatric
      Urology meetings with the purpose to  give answers  to the questions what the
      best treatment is for VUR, at what age the treatment is advocated, does it
      prevent for febrile urinary tract infections (UTI's)  and does it  stop of
      decreases the risk for reflux nefropathy and renal scars Well known are the
      International Reflux Study (1981) with a European and an American arm in  which
      the researchers compared medical approaches with surgical  approaches to reflux,
      and the Birmingham Reflux study (1987) which was a prospective trial of operative
      versus non-operative treatment of severe  vesicoureteric  reflux in children with
      five years observation (2). In 2009 the group from John Hopkins (Baltimore, USA)
      published their interim results from a randomized placebo-controlled study of
      children with  VUR (the RIVUR Study) (3).  The most recent randomized controlled
      trial (RCT) is the Swedish Reflux Trial published in the Journal of Urology 2010,
      July. This was set up as a RCT  to compare 3  treatment alternatives, including
      antibiotic prophylaxis, endoscopic therapy and surveillance as the control group,
      in regard to recurrent febrile UTIs, renal  damage  and VUR status after 2 years
      (4). Since these new data are available, we want to give an update in this
      specific and interesting field in Pediatric Urology.

PMID- 22619136
TI  - [Editorial Comment. Vesicoureteric reflux (VUR) in children: where are we now?].

PMID- 22619138
TI  - Testicular cancer: our experience after 10 years.
AB  - OBJECTIVES: Testicular cancer represents about 1% of malignant tumors in men. Of
      these tumors 95% are germ cell tumors (GCTs), which have a  maximum incidence
      between the second and third decades of life. Our objective was to carry out a
      retrospective analysis of testicular tumor cases that had been diagnosed in our
      Health Area between the years 2000 and 2010. METHODS: We performed a
      retrospective descriptive study between the years 2000 and 2010 analyzing 43
      patients treated for testicular cancer, including in the analysis  tumor
      incidence, the patient's age, clinic attended, patient's time until appointment,
      presence of tumor markers, patient's time before treatment, use of testicular
      prostheses, histological type and their typical characteristics, oncological
      treatment, tumor progression and mortality rate. RESULTS: We found an incidence
      of 4-5 cases/100,000 population/year in our Health Area. Two-thirds of the cases
      were detected in Stage I,  and 100%  of these cases showed  complete remission.
      Among those with higher stage tumors, two out of three patients were cured after
      chemotherapy. For the remaining one-third, rescue treatments  managed  to achieve
      a remission rate of 66%. Mortality was low and was linked to lymphoma or
      metastatic dissemination. CONCLUSION: The trend towards early diagnosis with
      detection during the initial cancer stages, together with current chemotherapy
      protocols, enables a high cure rate for  testicular cancer. Mortality in our
      series was associated with primary or secondary lymphomas.

PMID- 22619137
TI  - Effect of intrarectal povidone-iodine in the incidence of infectious
      complications after transrectal prostatic biopsy.
AB  - OBJECTIVES: To assess the incidence of genitourinary infections associated with
      transrectal ultrasound-guided prostate biopsy (TRUS-BX) using endorectal povidone
      iodine gel as a bactericidal agent. METHODS: We prospectively studied a total of
      530 patients who were given 30g of 10% povidone-iodine intrarectally before TRUS
      BX. Each patient received antibiotic prophylaxis with ciprofloxacin, starting the
      previous day (1g/day x 3 days), as well as cleansing enemas. RESULTS: One patient
      (0.20%) presented with an E. coli acute bacterial epididymitis after biopsy.
      CONCLUSIONS: In our study, the intrarectal use of 10% povidone-iodine gel in TRUS
      BX is associated with a much lower rate of infectious complications compared to
      those described in recent literature.

PMID- 22619139
TI  - Female sexual and pelvic floor muscles dysfunctions in familial amyloidotic
      polyneuropathy (FAP-Portuguese type).
AB  - OBJECTIVES: The aim of this study was to investigate the prevalence of Sexual and
      Pelvic Floor Dysfunctions associated with familial type 1 Portuguese amyloid
      polyneuropathy (FAP). We studied women with FAP in three stages of the disease:
      asymptomatic women (n=12), women in the early stage of the disease (n=8) and 3
      women in the most progressive stage of the disease. We hypothesize that women
      with FAP suffer from pelvic floor hypotonicity, which may hinder orgasmic
      function and as such, lead to deteriorated sexual function. METHODS: Twenty-three
      women with FAP were studied. Clinical examinations were performed using the
      following scales: Clinical Evaluation Scale (CES), Visual Analog Scale of Quality
      of Life (VAS), Female Sexual Function Index (FSFI) and Pelvic Floor Manometry
      (PFM). RESULTS: Of the women, 5 (21.7%) had a score of < 26 on the FSFI,
      suggesting sexual dysfunction, 3 of which had FAP at the most progressive stage.
      None of the asymptomatic women had low FSFI scores. The manometrical rates (PFM)
      of tonus and strength of the pelvic floor showed significant differences between
      groups. CONCLUSION: Female sexual dysfunction (FSD) may occur in the initial
      stages of the disease but is more prevalent in women in the advanced stages of
      the disease. There is an increasing incidence of FSD as FAP disease progresses,
      namely in terms of HSDD and orgasmic sensation. In the asymptomatic group, the
      females revealed PFM alterations without stress urinary incontinence, which is
      regarded to be a discrete deterioration of pelvic floor muscle function.

PMID- 22619140
TI  - Impossible bladder catheter removal. What can we do?
AB  - OBJECTIVE: The inability to remove a bladder catheter due to impossible balloon
      removal is a situation with controversial management; there are no action
      guidelines  and it is limited to individual experience in most cases. In this
      article, we review the techniques described for removing a urethral catheter and
      we share our experience  with one case. METHODS: A 70-year-old male with
      permanent bladder catheter was referred to the emergency department due to an
      inability to deflate the self-retaining  balloon during routine change in his
      health centre. RESULTS: After unsuccessfully trying to puncture the balloon
      through the inflation channel previously cut above the valve, we punctured it via
      the suprapubic route  under ultrasound guidance with a biopsy needle. Using this
      technique, we managed to rupture the balloon without free fragments, enabling the
      catheter to be changed without  incident. CONCLUSIONS: There are various
      techniques for approaching this situation, the knowledge of which enables the
      urologist to resolve the problem by adapting to patient's  characteristics and
      available resources. Suprapubic puncture of the self-retaining balloon is an
      easily reproducible technique with minimal complications and a lower  rate of
      free fragments.

PMID- 22619141
TI  - Giant retroperitoneal sarcoma: case report.
AB  - OBJECTIVE: To report a new case of giant retroperitoneal mass with silent
      beginning. METHODS: We present the case of a 36 year old man with a giant
      retroperitoneal liposarcoma 35 * 15 cm in size. The only symptom was a one month
      history of minimal  abdominal pain. CONCLUSION: Liposarcoma is the most frequent
      retroperitoneal mass. In most of the cases clinical symptoms are silent, being
      this the reason why diagnosis is late  and the size is large. The best image
      options are CT scan or MRI but final diagnosis is based on pathology results. Its
      treatment is surgery and relapse is very  usual.

PMID- 22619142
TI  - Minimally invasive retrieval of a retained Jackson--Pratt drainage tube using the
      Sachse urethrotome.
AB  - OBJECTIVE: A retained postoperative drain tube, trapped by one or more of the
      sutures of the abdominal wall closure, is a rare complication of frustrating 
      consequences and potential legal repercussions. There are few reports of
      techniques for minimally invasive removal of an anchored postoperative drain
      tube,  which not infrequently has been treated by reopening the wound.
      METHOD/RESULT: A 75 years-old man with a left T2-T3N0M0 renal carcinoma was
      treated with transperitoneal laparoscopic nephrectomy and a Jackson-Pratt  drain 
      was left  in place. Drain removal the day after revealed impossible, as if being
      caught with fascial suture. With the patient under sedation, we introduced a
      Sachse  urethrotome parallel to the drain, and the abdominal fascia was
      identified, then the polyglycolic stitch anchoring it to the wall could be
      severed, freeing the drain. CONCLUSIONS: Percutaneous extraction with the Sachse
      urethrotome of an anchored postoperative drain, should be the first option,
      before trying a forced  traction or using more complex options. This technique is
      for the first time published in the Spanish bibliography, and we think this
      possibility should be  disclosed to abdominal surgeons.

PMID- 22619143
TI  - Urachal adenocarcinoma. Case report and bibliographic review.
AB  - OBJECTIVE: Literature review of adenocarcinoma of the urachus in connection with
      two cases recently diagnosed and treated in our center. METHODS/RESULTS: We
      report 2 cases of urachus Adenocarcinoma treated in our institution, both
      underwent extended partial cystectomy including excision of the urachus up to the
      umbilicus. CONCLUSION: Urachal adenocarcinoma is an exceptional tumor, of poor
      prognosis, the treatment of which is surgical (partial cystectomy), and the main 
      predictors of disease-free survival are the degree of tumor differentiation and
      the free margins of the surgical specimen.

PMID- 22619144
TI  - Syringocele in adult patient. Case report.
AB  - OBJECTIVE: To describe one case of syringocele in an adult patient.
      METHODS/RESULTS: We report the case of a 26 year old man who presented frequency,
      hematuria and fever during one year, mictional cystourethrography showed a
      syringocele.  Treatment consisted in endoscopic surgery, with good results in the
      follow-up. CONCLUSIONS: The syringocele is a relatively infrequent entity, that
      is necessary to study in a young patient with voiding symptoms, accompanied or
      not of haematuria and  fever. The diagnosis is based on the cystourethrography,
      and treatment consisted, usually, in endoscopic surgery.

PMID- 22619145
TI  - The use of ultrasound with potentiator media in the diagnosis of complex cystic
      lesions.

PMID- 22619146
TI  - Suprapubic fibroma after prostatic adenomectomy.

PMID- 22619147
TI  - Cigarette quitlines, taxes, and other tobacco control policies: a state-level
      analysis.
AB  - This paper estimates monthly quitline calls using panel data at the state level
      from January 2005 to June 2010. Calls to state quitline numbers (or 1-800
      QUITNOW) were measured per million adult smokers in each state. The policies
      considered include excise taxes, workplace and public smoking bans, and a Peter
      Jennings television-based program warning of the health risks of smoking. We
      found that people anticipating increases in prices begin attempting to quit by
      calling quitlines. Finally, the Peter Jennings media campaign was highly
      correlated with quitline calls.

PMID- 22619149
TI  - High-resolution multi-isotope imaging mass spectrometry enables visualisation of
      stem cell division and metabolism.
AB  - MIMS visualises metabolism: A recent publication by Steinhauser and co-workers
      presents a novel application of multi-isotope mass spectrometry (MIMS) to
      visualise physiological metabolism in live mammalian organisms, and validate the
      "immortal strand hypothesis" of asymmetric chromosomal division of stem cells in
      the small intestine.

PMID- 22619150
TI  - Revisiting the specificity of an alpha-(1->4)-mannosyltransferase involved in
      mycobacterial methylmannose polysaccharide biosynthesis.
AB  - In order to evaluate the proposed biosynthetic pathway for the methylmannose
      (MMPs) polysaccharides produced by mycobacteria, two homologous series of
      synthetic alpha-(1->4)-linked 3-O-methyl-mannopyranosides, one terminated at the
      non-reducing end by a free mannopyranose residue (unmethylated oligosaccharides;
      OS) and the other terminated by a 3-O-methyl-mannopyranose residue (methylated
      OS), were prepared and evaluated as potential acceptors of an alpha-(1->4)
      mannosyltransferase. Using a mycobacterial membrane preparation as the source of
      the transferase, it was found that unmethylated OS are better substrates for the
      enzyme compared to the methylated OS of the same length. These results are
      inconsistent with the proposed MMP biosynthetic pathway, which suggests only
      methylated OS are acceptors of this transferase. To confirm that the observed
      activity arose from the desired alpha-(1->4)-mannosyltransferase, as opposed to
      other mannosyltransferases present in the membrane preparation, the products
      resulting from tetrasaccharides 4 (unmethylated OS) and 9 (methylated OS), which
      only differ in the terminal residue, were further analyzed. MALDI-MS, exo
      glycosidase digestion and (1) H NMR spectroscopy were used to evaluate the
      structures of these reaction products. These experiments revealed that the
      enzymatic products of both 4 and 9 contain only alpha-(1->4)-linked mannose
      residues, confirming the activity of the alpha-(1->4)-mannosyltransferase. This
      supports the finding that both methylated and unmethylated OS are acceptors of
      the enzyme. It was also demonstrated that a homologous series of oligosaccharides
      with different number of mannose residues were formed from both 4 and 9, as
      opposed to a single reaction product. These results, again, challenge the
      previously proposed MMP biosynthetic pathway involving alternating methylation
      and mannosylation reactions.

PMID- 22619153
TI  - Histologic follow-up of nondiagnostic thyroid fine needle aspirations:
      implications for adequacy criteria.
AB  - There is limited histologic follow-up for adequacy criteria in thyroid fine
      needle aspirations. We correlated the number of benign follicular cells in
      nondiagnostic aspirates (excluding atypical and Hurthle cells) and the results of
      histologic follow-up. A total of 170 cases with only benign follicular cells were
      reviewed. The sensitivity and specificity for 60 benign follicular cells was 97%
      and 42%. If the threshold for adequacy was lowered to 10 cells, the specificity
      of a benign diagnosis increased significantly (42% to 50%, P < 0.001) without a
      significant change in sensitivity (97% to 96%, P = 0.45). An additional 63 cases
      were diagnosed as adequate with three false negative cases. Lowering the
      threshold to 30 cells had no change in sensitivity (97%), increased specificity
      to 45% but this was not significant (P = 0.08). An additional 26 aspirates could
      be diagnosed as adequate without any false negative cases. Histologic follow-up
      suggests that the current criteria for adequacy can be lowered to improve
      specificity while retaining excellent sensitivity.

PMID- 22619154
TI  - Cytological findings of intrathyroidal epithelial thymoma/carcinoma showing
      thymus-like differentiation: a study of eight cases.
AB  - The purpose of this article is to describe the cytologic findings of
      intrathyroidal epithelial thymoma/carcinoma showing thymus-like differentiation
      (ITET/CASTLE) in detail and discuss its differential diagnoses. We examined
      cytologic specimens taken from eight ITET/CASTLE cases, who underwent fine needle
      aspiration. Cytologic features of ITET/CASTLE include (1) hypercellularity, (2)
      large cell clusters without papillary or follicular pattern, (3) round or spindle
      tumor cells with distinct nucleoli and cell border, (4) few keratinized cells and
      intracytoplasmic lumina (ICL), and (5) lymphocytic background. The differential
      diagnoses included poorly differentiated carcinoma, metastatic lymphoepithelioma,
      squamous cell carcinoma, and mucoepidermoid carcinoma. The presence of individual
      keratinizing cells and ICL and the location of the tumor may be helpful in
      indicating ITET/CASTLE.

PMID- 22619155
TI  - Fine-needle aspiration of thyroid tumors: identifying factors associated with
      adequacy rate in a large academic center in the Netherlands.
AB  - The goal of our study was to evaluate, and identify factors associated with, the
      adequacy rate of fine-needle aspiration (FNA) cytology of thyroid tumors to
      improve the quality of the procedure. We reviewed 1,611 cytological pathology
      reports of thyroid tumors of 871 patients between January 1998 and August 2008.
      The overall cytological adequacy rate was 53.9%. The freehand technique had
      significantly higher adequacy rates than the ultrasound (US)-guided technique (P
      < 0.001) regardless of size, tumor type, multinodularity, or location.
      Aspiration, performing specialist (endocrinologist versus radiologist), and size
      were the factors associated with adequacy rates. US-guided FNA is recommended in
      previous articles, but results in our clinic were in favor of freehand FNA. US
      guidance is a way to improve adequacy rates, but we would like to stress the
      importance of other factors like operator experience, education, and quality
      control in one's own institution before implementing techniques.

PMID- 22619156
TI  - Correlation of thyroid nodule fine-needle aspiration cytology with corresponding
      histology at Mayo Clinic, 2001-2007: an institutional experience of 1,945 cases.
AB  - Following the National Cancer Institute Thyroid Fine Needle Aspiration State of
      the Science Conference, the thyroid fine-needle aspiration biopsy (FNAB) practice
      at Mayo Clinic, Rochester, Minnesota, conducted retrospective analyses
      correlating cytologic and histologic evaluations of thyroid nodules. Cytologic
      and histologic reports were retrieved for patients with thyroid nodules who
      underwent thyroid FNAB between January 2001 and December 2007, with subsequent
      surgical thyroid resection. Cases were classified by major cytologic and
      histologic diagnosis and specific diagnostic subcategories. Of 1,945 FNAB
      cytologic results, 180 (9.3%) were nondiagnostic; 512 (26.3%) were negative for
      malignancy; 27 (1.4%) were atypical; 729 (37.5%) were suspicious for malignancy;
      and 497 (25.6%) were positive for malignancy. Histology was benign in 1,179
      (60.6%) and malignant in 766 (39.4%). For thyroid malignancy as the disease
      outcome, at cytologic thresholds of atypical, suspicious, and positive, overall
      sensitivity of thyroid FNAB was 94.5%, 94.1%, and 65.0%, respectively, and
      specificity was 46.0%, 48.3%, and 98.5%, respectively. Positive predictive value
      for all malignancies was 97.0%, and negative predictive value was 92.0%. When
      separated by specific malignant outcomes, diagnoses of papillary carcinoma,
      medullary carcinoma, and lymphoma had specificity of suspicious FNAB diagnoses
      ranging from 90.5% to 99.6%; positive predictive value ranged from 87.5% to
      91.4%. For follicular or Hurthle carcinoma, suspicious FNAB diagnoses had a
      specificity of 52.5% and a positive predictive value of 5.9%. Sensitivity of
      indeterminate FNAB diagnoses ranged from 72.7% to 95.3%. For follicular or
      Hurthle pattern malignancies, indeterminate cytologic diagnoses should be
      interpreted with caution by the clinician considering surgical management. Diagn.
      Cytopathol. 2012;40:E27-E32. (c) 2010 Wiley Periodicals, Inc.

PMID- 22619158
TI  - Diagnostic usefulness of fragments of crushed cells in autoimmune thyroiditis.
AB  - Fine-needle aspiration cytology has emerged as an important diagnostic tool in
      cases of autoimmune thyroiditis. However, the patchy nature of this disease and
      its coexistence with other thyroid pathologies, with only subtle demonstrable
      cytologic features in many cases can lead to misdiagnosis. Of 313 thyroid
      aspirates, 62 were diagnosed as autoimmune thyroiditis. Fragments of crushed
      cells were observed in 51 (82.11%) of autoimmune thyroiditis (P < 0.001). The
      presence of "crush artifact" that can be easily picked up on low magnification
      should be used as an important criterion for the diagnosis of thyroiditis. It is
      particularly helpful in cellular smears from thyroiditis to avoid misdiagnosis of
      neoplasia.

PMID- 22619157
TI  - Fine-needle aspiration in the evaluation of thyroid lesions in children.
AB  - The role of fine-needle aspiration (FNA) cytology in the evaluation of thyroid
      lesions in not as well established in children when compared with adults. Hence
      we aimed to ascertain the utility and limitations of FNA in childhood thyroid
      lesions. This was a retrospective analysis of all thyroid FNA performed in
      children less than 14 years of age over a 4-year period (2005-2009).
      Histopathological follow-up was available in six cases. A total of 77 cases were
      included in the analysis. The most common cytological diagnosis was lymphocytic
      thyroiditis (49.3%), followed by colloid goiter (18.2%), hyperplasia (10.4%), and
      benign aspirate (7.8%); malignancy was identified in six cases (7.8%). Of these
      six cases, three were papillary thyroid carcinoma. There was one false-positive
      case reported as a Hurthle-cell neoplasm, which on histology showed Hashimoto's
      thyroiditis. One case each of rhabdomyosarcoma and spindle epithelial tumor with
      thymus like differentiation was wrongly diagnosed as thyroid neoplasm, NOS, and
      medullary carcinoma (spindle variant), respectively. The overall diagnostic
      accuracy was 98.6% with 100% sensitivity, 98.6% specificity, 80% positive
      predictive value, and 100% negative predictive value. FNA is extremely valuable
      in the initial evaluation of thyroid swelling in children. Rare neoplasms
      masquerading as thyroid nodules in children can pose difficulties in diagnosis;
      however, papillary carcinoma is easily recognized. In lymphocytic thyroiditis, it
      provides a tissue diagnosis, thereby avoiding more invasive procedure for merely
      diagnostic purposes.

PMID- 22619159
TI  - Preoperative cytologic diagnosis of papillary thyroid carcinoma with mixed
      columnar cell and tall cell features.

PMID- 22619160
TI  - Does insecticide drift adversely affect grasshoppers (Orthoptera: Saltatoria) in
      field margins? A case study combining laboratory acute toxicity testing with
      field monitoring data.
AB  - The current terrestrial risk assessment of insecticides regarding nontarget
      arthropods considers exclusively beneficial organisms, whereas herbivorous
      insects, such as grasshoppers, are ignored. However, grasshoppers living in field
      margins or meadows adjacent to crops may potentially be exposed to insecticides
      due to contact with or ingestion of contaminated food. Therefore, the present
      study assessed effects of five active ingredients of insecticides (dimethoate,
      pirimicarb, imidacloprid, lambda-cyhalothrin, and deltamethrin) on the survival
      of Chorthippus sp. grasshopper nymphs by considering two routes of exposure
      (contact and oral). The experiments were accompanied by monitoring field margins
      that neighbored cereals, vineyards, and orchards. Grasslands were used as
      reference sites. The laboratory toxicity tests revealed a sensitivity of
      grasshoppers with regard to the insecticides tested in the present study similar
      to that of the standard test species used in arthropod risk assessments. In the
      field monitoring program, increasing grasshopper densities were detected with
      increasing field margin width next to cereals and vineyards, but densities
      remained low over the whole range of field margins from 0.5 to 20 m next to
      orchards. Grasshopper densities equivalent to those of grassland sites were only
      observed in field margins exceeding 9 m in width, except for field margins next
      to orchards. These results may indicate that current insecticide risk assessments
      are insufficiently protective for grasshoppers in field margins.

PMID- 22619164
TI  - Family experience with difficult decisions in end-of-life care.
AB  - OBJECTIVE: The difficult decisions encountered by family caregivers in the
      process of care for patients with terminal cancer are seldom studied.
      Investigating their experiences with difficult decisions may help relieve their
      psychological distress. The purpose of this study was to determine the frequency
      and difficulty of decisions experienced in end-of-life care and to identify
      related factors. METHODS: A cross-sectional study using questionnaires was
      conducted with family caregivers of patients who died of cancer in a university
      hospital. Difficulty of decisions and relevant influencing variables including
      demographic data, knowledge in palliative care and the Natural Death Act, and
      beliefs on the Natural Death Act were measured. RESULTS: A total of 302 bereaved
      family caregivers were included in the final analysis. The most difficult
      decisions commonly encountered in both hospice and non-hospice wards related to
      truth telling, place of care, and alternative treatments. Logistic regression
      analysis demonstrated that older age (odds ratio = 0.92, 95% confidence interval
      = 0.89-0.95), not being the main family caregiver (0.20, 0.06-0.62), and less
      perception of burdens regarding the Natural Death Act (0.61, 0.37-0.99) were
      negatively correlated with the difficulty of decisions. CONCLUSIONS: Families
      frequently encountered difficult decisions while caring for terminally ill loved
      ones. Better communication with family members, particularly the main caregiver,
      to diminish negative perceptions of the Natural Death Act could help to decrease
      psychological distress.

PMID- 22619165
TI  - The complex of cytochrome f and plastocyanin from Nostoc sp. PCC 7119 is highly
      dynamic.
AB  - Cytochrome f (Cyt f) and plastocyanin (Pc) form a highly transient complex as
      part of the photosynthetic redox chain. The complex from Nostoc sp. PCC 7119 was
      studied by NMR relaxation spectroscopy with the aim of determining the
      orientation of Pc relative to Cyt f. Chemical-shift-perturbation analysis showed
      that the presence of spin labels on the surface of Cyt f does not significantly
      affect the binding of Pc. The paramagnetic relaxation enhancement results are not
      consistent with a single orientation of Pc, thus indicating that multiple
      orientations must occur and suggesting that an encounter state represents a large
      fraction of the complex.

PMID- 22619166
TI  - Long-term evaluation of respiratory status after esophageal atresia repair.
AB  - RATIONALE: Esophageal atresia (EA) is a congenital malformation. Nowadays, its
      initial prognosis is excellent thanks to improvements in neonatal and surgical
      management. However, the assessment of long-term respiratory outcome has become
      necessary in affected children and was thus performed in this study. The benefits
      of cardiopulmonary function testing were also examined. METHODS: The medical
      records of 77 children operated on for EA between 1990 and 2004 were reviewed.
      The results of respiratory function testing and cardiopulmonary response to
      effort were collected, together with neonatal and anthropometric data. RESULTS:
      Acceptable measurements were obtained in 31 children with EA. These children were
      comparable to the ones lost during follow-up. The results of pulmonary function
      tests (PFTs) were abnormal in 21 cases (68%). A poor ventilatory response was
      detected in 14 children (45%) by cardiopulmonary function testing. Ten children
      who had abnormal results on PFTs were not under any anti-asthmatic treatment.
      CONCLUSIONS: Impaired lung function was noted in children with repaired EA.
      Indeed, cardiopulmonary function tests results correlated with standard
      spirometric parameters and revealed minimal clinical symptoms. Moreover, many
      children with EA had a limited ventilatory reserve (VR). These results indicate
      that respiratory symptoms are often neglected in children with repaired EA and
      reinforce the need to provide adequate treatment.

PMID- 22619167
TI  - CVD-grown horizontally aligned single-walled carbon nanotubes: synthesis routes
      and growth mechanisms.
AB  - Single-walled carbon nanotubes (SWCNTs) have attractive electrical and physical
      properties, which make them very promising for use in various applications. For
      some applications however, in particular those involving electronics, SWCNTs need
      to be synthesized with a high degree of control with respect to yield, length,
      alignment, diameter, and chirality. With this in mind, a great deal of effort is
      being directed to the precision control of vertically and horizontally aligned
      nanotubes. In this review the focus is on the latter, horizontally aligned tubes
      grown by chemical vapor deposition (CVD). The reader is provided with an in-depth
      review of the established vapor deposition orientation techniques. Detailed
      discussions on the characterization routes, growth parameters, and growth
      mechanisms are also provided.

PMID- 22619168
TI  - Design and function of pre-organised outer-sphere amidopyridyl extractants for
      zinc(II) and cobalt(II) chlorometallates: the role of C-H hydrogen bonds.
AB  - Four new sterically hindered pyridines, L(1)-L(4)-containing amido substituents
      at the 2-position act as efficient solvent extractants for [CoCl(4)](2-) or
      [ZnCl(4)](2-) from acidic chloride solutions through protonation of the pyridino
      N-centre to form the neutral outer-sphere complexes [(LH)(2)MCl(4)]. These
      ionophores show very high selectivity for chlorometallate anions over chloride
      ion and are readily stripped to liberate the free-metal chlorides without the
      formation of inner-sphere complexes [ML(2)Cl(2)]. Single-crystal X-ray structure
      determinations of [(L(2)H)(2)CoCl(4)] and [(L(2)H)(2)ZnCl(4)] (L(2) = 2-(4,6-di
      tert-butylpyridin-2-yl)-N,N'-dihexylmalonamide) coupled with (1)H NMR
      spectroscopy and DFT calculations on L(2)H(+) and other complexes of [ZnCl(4)](2
      ) confirm that the pyridinium NH group does not address the outer co-ordination
      sphere of the metallanion, but rather forms a hydrogen bond to the pendant amide
      groups and thus pre-organizes the ligand to present both C-H and amido N-H
      hydrogen-bond donors to the [MCl(4)](2-) ions. The selectivity for
      chlorometallates over chloride ions shown by this class of extractants arises
      from their ability to present several polarized C-H units towards the charge
      diffuse ions [MCl(4)](2-), whereas the smaller, "harder" chloride anion prefers
      to be associated with the amido N-H hydrogen-bond donors.

PMID- 22619169
TI  - Histone monoubiquitylation position determines specificity and direction of
      enzymatic cross-talk with histone methyltransferases Dot1L and PRC2.
AB  - It is well established that chromatin is a destination for signal transduction,
      affecting many DNA-templated processes. Histone proteins in particular are
      extensively post-translationally modified. We are interested in how the complex
      repertoire of histone modifications is coordinately regulated to generate
      meaningful combinations of "marks" at physiologically relevant genomic locations.
      One important mechanism is "cross-talk" between pre-existing histone post
      translational modifications and enzymes that subsequently add or remove
      modifications on chromatin. Here, we use chemically defined "designer"
      nucleosomes to investigate novel enzymatic cross-talk relationships between the
      most abundant histone ubiquitylation sites, H2AK119ub and H2BK120ub, and two
      important histone methyltransferases, Dot1L and PRC2. Although the presence of
      H2Bub in nucleosomes greatly stimulated Dot1L methylation of H3K79, we found that
      H2Aub did not influence Dot1L activity. In contrast, we show that H2Aub inhibited
      PRC2 methylation of H3K27, but H2Bub did not influence PRC2 activity. Taken
      together, these results highlight how the position of nucleosome
      monoubiquitylation affects the specificity and direction of cross-talk with
      enzymatic activities on chromatin.

PMID- 22619170
TI  - Expression of a truncated form of the endoplasmic reticulum chaperone protein,
      sigma1 receptor, promotes mitochondrial energy depletion and apoptosis.
AB  - The sigma1 receptor (sigma(1)R) regulates endoplasmic reticulum
      (ER)/mitochondrial interorganellar Ca(2+) mobilization through the inositol 1,4,5
      trisphosphate receptor (IP(3)R). Here, we observed that expression of a novel
      splice variant of sigma(1)R, termed short form sigma(1)R (sigma(1)SR), has a
      detrimental effect on mitochondrial energy production and cell survival.
      sigma(1)SR mRNA lacks 47 ribonucleotides encoding exon 2, resulting in a
      frameshift and formation of a truncated receptor. sigma(1)SR localizes primarily
      in the ER at perinuclear regions and forms a complex with sigma(1)R but not with
      IP(3)R in the mitochondrion-associated ER membrane. Overexpression of both
      sigma(1)R and the truncated isoform promotes mitochondrial elongation with
      increased ER mitochondrial contact surface. sigma(1)R overexpression increases
      the efficiency of mitochondrial Ca(2+) uptake in response to IP(3)R-driven
      stimuli, whereas sigma(1)SR overexpression reduces it. Most importantly,
      sigma(1)R promotes ATP production via increased mitochondrial Ca(2+) uptake,
      promoting cell survival in the presence of ER stress. By contrast, sigma(1)SR
      suppresses ATP production following ER stress, enhancing cell death. Taken
      together, the newly identified sigma(1)SR isoform interferes with sigma(1)R
      function relevant to mitochondrial energy production under ER stress conditions,
      promoting cellular apoptosis.

PMID- 22619171
TI  - Proteolytic cleavage of extracellular alpha-synuclein by plasmin: implications
      for Parkinson disease.
AB  - Parkinson disease (PD) is the second most common neurodegenerative disease
      characterized by a progressive dopaminergic neuronal loss in association with
      Lewy body inclusions. Gathering evidence indicates that alpha-synuclein (alpha
      syn), a major component of the Lewy body, plays an important role in the
      pathogenesis of PD. Although alpha-syn is considered to be a cytoplasmic protein,
      it has been detected in extracellular biological fluids, including human
      cerebrospinal fluid and blood plasma of healthy and diseased individuals. In
      addition, a prion-like spread of alpha-syn aggregates has been recently proposed
      to contribute to the propagation of Lewy bodies throughout the nervous system
      during progression of PD, suggesting that the metabolism of extracellular alpha
      syn might play a key role in the pathogenesis of PD. In the present study, we
      found that plasmin cleaved and degraded extracellular alpha-syn specifically in a
      dose- and time- dependent manner. Aggregated forms of alpha-syn as well as
      monomeric alpha-syn were also cleaved by plasmin. Plasmin cleaved mainly the N
      terminal region of alpha-syn and also inhibited the translocation of
      extracellular alpha-syn into the neighboring cells in addition to the activation
      of microglia and astrocytes by extracellular alpha-syn. Further, extracellular
      alpha-syn regulated the plasmin system through up-regulation of plasminogen
      activator inhibitor-1 (PAI-1) expression. These findings help to understand the
      molecular mechanism of PD and develop new therapeutic targets for PD.

PMID- 22619172
TI  - A viral deubiquitylating enzyme restores dislocation of substrates from the
      endoplasmic reticulum (ER) in semi-intact cells.
AB  - Terminally misfolded glycoproteins are ejected from the endoplasmic reticulum
      (ER) to the cytosol and are destroyed by the ubiquitin proteasome system. A
      dominant negative version of the deubiquitylating enzyme Yod1 (Yod1C160S) causes
      accumulation of dislocation substrates in the ER. Failure to remove ubiquitin
      from the dislocation substrate might therefore stall the reaction at the exit
      site from the ER. We hypothesized that addition of a promiscuous deubiquitylase
      should overcome this blockade and restore dislocation. We monitored ER-to-cytosol
      transport of misfolded proteins in cells permeabilized at high cell density by
      perfringolysin O, a pore-forming cytolysin. This method allows ready access of
      otherwise impermeant reagents to the intracellular milieu with minimal dilution
      of cytoplasmic components. We show that addition of the purified Epstein-Barr
      virus deubiquitylase to semi-intact cells indeed initiates dislocation of a
      stalled substrate intermediate, resulting in stabilization of substrates in the
      cytosol. Our data provide new mechanistic insight in the dislocation reaction and
      support a model where failure to deubiquitylate an ER-resident protein occludes
      the dislocon and causes upstream misfolded intermediates to accumulate.

PMID- 22619173
TI  - Hydrophobic matching controls the tilt and stability of the dimeric platelet
      derived growth factor receptor (PDGFR) beta transmembrane segment.
AB  - The platelet-derived growth factor receptor beta is a member of the cell surface
      receptor tyrosine kinase family and dimerizes upon activation. We determined the
      structure of the transmembrane segment in dodecylphosphocholine micelles by
      liquid-state NMR and found that it forms a stable left-handed helical dimer.
      Solid-state NMR and oriented circular dichroism were used to measure the tilt
      angle of the helical segments in macroscopically aligned model membranes with
      different acyl chain lengths. Both methods showed that decreasing bilayer
      thickness (DEPC-POPC-DMPC) led to an increase in the helix tilt angle from 10
      degrees  to 30 degrees  with respect to the bilayer normal. At the same time,
      reconstitution of the comparatively long hydrophobic segment became less
      effective, eventually resulting in complete protein aggregation in the short
      chain lipid DLPC. Unrestrained molecular dynamics simulations of the dimer were
      carried out in explicit lipid bilayers (DEPC, POPC, DMPC, sphingomyelin),
      confirming the observed dependence of the helix tilt angle on bilayer thickness.
      Notably, molecular dynamics revealed that the left-handed dimer gets tilted en
      bloc, whereas conformational transitions to alternative (e.g. right-handed
      dimeric) states were not supported. The experimental data along with the
      simulation results demonstrate a pronounced interplay between the platelet
      directed growth factor receptor beta transmembrane segment and the bilayer
      thickness. The effect of hydrophobic mismatch might play a key role in the
      redistribution and activation of the receptor within different lipid microdomains
      of the plasma membrane in vivo.

PMID- 22619174
TI  - Abcb11 deficiency induces cholestasis coupled to impaired beta-fatty acid
      oxidation in mice.
AB  - The bile salt export pump (BSEP) is an ATP-binding cassette transporter that
      serves as the primary system for removing bile salts from the liver. In humans,
      deficiency of BSEP, which is encoded by the ABCB11 gene, causes severe
      progressive cholestatic liver disease from early infancy. In previous studies of
      Abcb11 deficiency in mice generated on a mixed genetic background, the animals
      did not recapitulate the human disease. We reasoned that ABCB11 deficiency may
      cause unique changes in hepatic metabolism that are predictive of liver injury.
      To test this possibility, we first determined that Abcb11 knock-out (KO) C57BL/6J
      mice recapitulate human deficiency. Before the onset of cholestasis, Abcb11 KO
      mice have altered hepatic lipid metabolism coupled with reduced expression of
      genes important in mitochondrial fatty acid oxidation. This was associated with
      increased serum free-fatty acids, reduced total white adipose, and marked
      impairment of long-chain fatty acid beta-oxidation. Importantly, metabolomic
      analysis confirmed that Abcb11 KO mice have impaired mitochondrial fatty acid
      beta-oxidation with the elevated fatty acid metabolites phenylpropionylglycine
      and phenylacetylglycine. These metabolic changes precede cholestasis but may be
      of relevance to cholestatic disease progression because altered fatty acid
      metabolism can enhance reactive oxygen species that might exacerbate cholestatic
      liver damage.

PMID- 22619175
TI  - Threonine-120 phosphorylation regulated by phosphoinositide-3-kinase/Akt and
      mammalian target of rapamycin pathway signaling limits the antitumor activity of
      mammalian sterile 20-like kinase 1.
AB  - Mst1/Stk4, a hippo-like serine-threonine kinase, is implicated in many cancers,
      including prostate cancer. However, the mechanisms regulating Mst1 remain
      obscure. Here, we characterized the effects of phospho-Thr-120 on Mst1 in
      prostate cancer cells. We demonstrated that phospho-Thr-120 did not alter the
      nuclear localization or cleavage of Mst1 in a LNCaP or castration-resistant C4-2
      prostate tumor cell model, as revealed by a mutagenesis approach. Phospho-Thr-120
      appeared to be specific to cancer cells and predominantly localized in the
      nucleus. In contrast, phospho-Thr-183, a critical regulator of Mst1 cell death,
      was exclusively found in the cytoplasm. As assessed by immunohistochemistry, a
      similar distribution of phospho-Mst1-Thr-120/Thr-183 was also observed in a
      prostate cancer specimen. In addition, the blockade of PI3K signaling by a small
      molecule inhibitor, LY294002, increased cytoplasmic phospho-Mst1-Thr-183 without
      having a significant effect on nuclear phospho-Mst1-Thr-120. However, the
      attenuation of mammalian target of rapamycin (mTOR) activity by a selective
      pharmacologic inhibitor, Ku0063794 or CCI-779, caused the up-regulation of
      nuclear phospho-Mst1-Thr-120 without affecting cytoplasmic phospho-Mst1-Thr-183.
      This suggests that PI3K and mTOR pathway signaling differentially regulate
      phospho-Mst1-Thr-120/Thr-183. Moreover, mutagenesis and RNAi data revealed that
      phospho-Thr-120 resulted in C4-2 cell resistance to mTOR inhibition and reduced
      the Mst1 suppression of cell growth and androgen receptor-driven gene expression.
      Collectively, these findings indicate that phospho-Thr-120 leads to the loss of
      Mst1 functions, supporting cancer cell growth and survival.

PMID- 22619176
TI  - Central role of mitofusin 2 in autophagosome-lysosome fusion in cardiomyocytes.
AB  - In the heart, autophagy has been implicated in cardioprotection and ischemia
      reperfusion tolerance, and the dysregulation of autophagy is associated with the
      development of heart failure. Mitochondrial dynamic proteins are profoundly
      involved in autophagic processes, especially the initiation and formation of
      autophagosomes, but it is not clear whether they play any role in cardiac
      autophagy. We previously reported that mitofusin 2 (MFN2), a mitochondrial outer
      membrane protein, serves as a major determinant of cardiomyocyte apoptosis
      mediated by oxidative stress. Here, we reveal a novel and essential role of MFN2
      in mediating cardiac autophagy. We found that specific deletion of MFN2 in
      cardiomyocytes caused extensive accumulation of autophagosomes. In particular,
      the fusion of autophagosomes with lysosomes, a critical step in autophagic
      degradation, was markedly retarded without altering the formation of
      autophagosomes and lysosomes in response to ischemia-reperfusion stress.
      Importantly, MFN2 co-immunoprecipitated with RAB7 in the heart, and starvation
      further increased it. Knockdown of MFN2 by shRNA prevented, whereas re-expression
      of MFN2 restored, the autophagosome-lysosome fusion in neonatal cardiomyocytes.
      Hearts from cardiac-specific MFN2 knock-out mice had abnormal mitochondrial and
      cellular metabolism and were vulnerable to ischemia-reperfusion challenge. Our
      study defined a novel and essential role of MFN2 in the cardiac autophagic
      process by mediating the maturation of autophagy at the phase of autophagosome
      lysosome fusion; deficiency of MFN2 caused multiple molecular and functional
      defects that undermined cardiac reserve and gradually led to cardiac
      vulnerability and dysfunction.

PMID- 22619178
TI  - Special issue featuring selected papers from the International Workshop on Bio
      Inspired Robots (Nantes, France, 6-8 April 2011).

PMID- 22619177
TI  - Host proteolytic activity is necessary for infectious bursal disease virus capsid
      protein assembly.
AB  - In many viruses, a precursor particle, or procapsid, is assembled and undergoes
      massive chemical and physical modification to produce the infectious capsid.
      Capsid assembly and maturation are finely tuned processes in which viral and host
      factors participate. We show that the precursor of the VP2 capsid protein (pVP2)
      of the infectious bursal disease virus (IBDV), a double-stranded RNA virus, is
      processed at the C-terminal domain (CTD) by a host protease, the puromycin
      sensitive aminopeptidase (PurSA). The pVP2 CTD (71 residues) has an important
      role in determining the various conformations of VP2 (441 residues) that build
      the T = 13 complex capsid. pVP2 CTD activity is controlled by co- and
      posttranslational proteolytic modifications of different targets by the VP4 viral
      protease and by VP2 itself to yield the mature VP2-441 species. Puromycin
      sensitive aminopeptidase is responsible for the peptidase activity that cleaves
      the Arg-452-Arg-453 bond to generate the intermediate pVP2-452 polypeptide. A
      pVP2 R453A substitution abrogates PurSA activity. We used a baculovirus-based
      system to express the IBDV polyprotein in insect cells and found inefficient
      formation of virus-like particles similar to IBDV virions, which correlates with
      the absence of puromycin-sensitive aminopeptidase in these cells. Virus-like
      particle assembly was nonetheless rescued efficiently by coexpression of chicken
      PurSA or pVP2-452 protein. Silencing or pharmacological inhibition of puromycin
      sensitive aminopeptidase activity in cell lines permissive for IBDV replication
      caused a major blockade in assembly and/or maturation of infectious IBDV
      particles, as virus yields were reduced markedly. PurSA activity is thus
      essential for IBDV replication.

PMID- 22619180
TI  - Assembly of graphene sheets into 3D macroscopic structures.
AB  - Integration of graphene sheets, 2D nanoscale building blocks, into 3D macroscopic
      assemblies and ultimately into a functional system is essential to explore the
      advanced properties of individual graphene sheets for macroscopic applications.
      This Concept paper summarizes different ways, such as flow-directed assembly,
      layer-by-layer deposition, template-directed method, and leavening strategy to
      assemble graphene sheets into the layered and porous 3D macroscopic structures.
      The obtained structures show unique properties, such as flexible network, high
      specific surface area, and outstanding electrical and mechanical properties.
      Furthermore, the functional systems based on such graphene 3D macroscopic
      structures have shown enhanced performance in the applications of energy storage,
      catalysis, environmental remediation, and sensing.

PMID- 22619179
TI  - Effect of thermal stability on protein adsorption to silica using homologous aldo
      keto reductases.
AB  - Gaining more insight into the mechanisms governing the behavior of proteins at
      solid/liquid interfaces is particularly relevant in the interaction of high-value
      biologics with storage and delivery device surfaces, where adsorption-induced
      conformational changes may dramatically affect biocompatibility. The impact of
      structural stability on interfacial behavior has been previously investigated by
      engineering nonwild-type stability mutants. Potential shortcomings of such
      approaches include only modest changes in thermostability, and the introduction
      of changes in the topology of the proteins when disulfide bonds are incorporated.
      Here we employ two members of the aldo-keto reductase superfamily (alcohol
      dehydrogenase, AdhD and human aldose reductase, hAR) to gain a new perspective on
      the role of naturally occurring thermostability on adsorbed protein arrangement
      and its subsequent impact on desorption. Unexpectedly, we find that during
      initial adsorption events, both proteins have similar affinity to the substrate
      and undergo nearly identical levels of structural perturbation. Interesting
      differences between AdhD and hAR occur during desorption and both proteins
      exhibit some level of activity loss and irreversible conformational change upon
      desorption. Although such surface-induced denaturation is expected for the less
      stable hAR, it is remarkable that the extremely thermostable AdhD is similarly
      affected by adsorption-induced events. These results question the role of thermal
      stability as a predictor of protein adsorption/desorption behavior.

PMID- 22619181
TI  - A novel autonomous, bioinspired swimming robot developed by neuroscientists and
      bioengineers.
AB  - This paper describes the development of a new biorobotic platform inspired by the
      lamprey. Design, fabrication and implemented control are all based on
      biomechanical and neuroscientific findings on this eel-like fish. The lamprey
      model has been extensively studied and characterized in recent years because it
      possesses all basic functions and control mechanisms of higher vertebrates, while
      at the same time having fewer neurons and simplified neural structures. The
      untethered robot has a flexible body driven by compliant actuators with
      proprioceptive feedback. It also has binocular vision for vision-based
      navigation. The platform has been successfully and extensively experimentally
      tested in aquatic environments, has high energy efficiency and is ready to be
      used as investigation tool for high level motor tasks.

PMID- 22619182
TI  - Organometallic compounds: an opportunity for chemical biology?
AB  - Organometallic compounds are renowned for their remarkable applications in the
      field of catalysis, but much less is known about their potential in chemical
      biology. Indeed, such compounds have long been considered to be either unstable
      under physiological conditions or cytotoxic. As a consequence, little attention
      has been paid to their possible utilisation for biological purposes. Because of
      their outstanding physicochemical properties, which include chemical stability,
      structural diversity and unique photo- and electrochemical properties, however,
      organometallic compounds have the ability to play a leading role in the field of
      chemical biology. Indeed, remarkable examples of the use of such compounds
      notably as enzyme inhibitors and as luminescent agents-have recently been
      reported. Here we summarise recent advances in the use of organometallic
      compounds for chemical biology purposes, an area that we define as
      "organometallic chemical biology". We also demonstrate that these recent
      discoveries are only a beginning and that many other organometallic complexes are
      likely to be found useful in this field of research in the near future.

PMID- 22619183
TI  - Quantitative methods to characterize morphological properties of cell lines.
AB  - Descriptive terms are often used to characterize cells in culture, but the use of
      nonquantitative and poorly defined terms can lead to ambiguities when comparing
      data from different laboratories. Although recently there has been a good deal of
      interest in unambiguous identification of cell lines via their genetic markers,
      it is also critical to have definitive, quantitative metrics to describe cell
      phenotypic characteristics. Quantitative metrics of cell phenotype will aid the
      comparison of data from experiments performed at different times and in different
      laboratories where influences such as the age of the population and differences
      in culture conditions or protocols can potentially affect cellular metabolic
      state and gene expression in the absence of changes in the genetic profile. Here,
      we present examples of robust methodologies for quantitatively assessing
      characteristics of cell morphology and cell-cell interactions, and of growth
      rates of cells within the population. We performed these analyses with
      endothelial cell lines derived from dolphin, bovine and human, and with a mouse
      fibroblast cell line. These metrics quantify some characteristics of these cells
      lines that clearly distinguish them from one another, and provide quantitative
      information on phenotypic changes in one of the cell lines over large number of
      passages.

PMID- 22619186
TI  - Epidermal growth factor-ferritin H-chain protein nanoparticles for tumor active
      targeting.
AB  - Human ferritin H-chain protein (FTH1)-based nanoparticles possess a precisely
      assembled nanometer-scale structure and high safety. However, their applications
      for imaging and drug delivery towards cancer cells remain limited due to a lack
      of target specificity. Epidermal growth factor receptor (EGFR) is overexpressed
      in many malignant tissues including breast cancer, and has been used as a
      therapeutic target for cancer treatment. Herein, a genetic method is shown to
      generate EGF-FTH1 chimeric proteins. EGF-FTH1 nanoparticles with EGF on the
      surface are then produced. The data demonstrate that EGF-FTH1 nanoparticles, with
      a small size (11.8 +/- 1.8 nm), narrow size distribution, and high biosafety, can
      specifically bind to and then be taken up by breast cancer MCF-7 cells and MDA-MB
      231 cells, but not normal breast epithelial MCF-10A cells. In contrast, binding
      and absorption of nontargeted ferritin-based nanoparticles to breast cancer cells
      are negligible. In vivo studies show that EGF-FTH1 nanoparticles are accumulated
      in breast tumors in a mouse xenograft model. Interestingly, the concentration of
      EGF-FTH1 nanoparticles in the tumor site is significantly reduced when mice are
      pretreated with an excess of free EGF. These results imply that EGF-EGFR
      interaction plays an important role in regulating the tumor retention of EGF-FTH1
      nanoparticles.

PMID- 22619184
TI  - Mannosylglycerate stabilizes staphylococcal nuclease with restriction of slow
      beta-sheet motions.
AB  - Mannosylglycerate is a compatible solute typical of thermophilic marine
      microorganisms that has a remarkable ability to protect proteins from thermal
      denaturation. This ionic solute appears to be a universal stabilizing agent, but
      the extent of protection depends on the specific protein examined. To understand
      how mannosylglycerate confers protection, we have been studying its influence on
      the internal motions of a hyperstable staphylococcal nuclease (SNase).
      Previously, we found a correlation between the magnitude of protein stabilization
      and the restriction of fast backbone motions. We now report the effect of
      mannosylglycerate on the fast motions of side-chains and on the slower unfolding
      motions of the protein. Side-chain motions were assessed by (13)CH(3) relaxation
      measurements and model-free analysis while slower unfolding motions were probed
      by H/D exchange measurements at increasing concentrations of urea. Side-chain
      motions were little affected by the presence of different concentrations of
      mannosylglycerate or even by the presence of urea (0.25M), and show no
      correlation with changes in the thermodynamic stability of SNase. Native hydrogen
      exchange experiments showed that, contrary to reports on other stabilizing
      solutes, mannosylglycerate restricts local motions in addition to the global
      motions of the protein. The protein unfolding/folding pathway remained
      undisturbed in the presence of mannosylglycerate but the solute showed a specific
      effect on the local motions of beta-sheet residues. This work reinforces the link
      between solute-induced stabilization and restriction of protein motions at
      different timescales, and shows that the solute preferentially affects specific
      structural elements of SNase.

PMID- 22619187
TI  - Recombinant production of isotope-labeled peptides and spontaneous cyclization of
      amino-terminal glutamine into pyroglutamic acid.

PMID- 22619188
TI  - Purification of IgG and albumin from human plasma by aqueous two phase system
      fractionation.
AB  - The current shortages in human plasma products at global levels justify the
      development of new, cost effective plasma fractionation methods. We have
      developed a fractionation process to obtain immunoglobulin G (IgG) and albumin
      enriched fractions based on polymer-salt aqueous two phase system (ATPS). A small
      scale (0.02 L) ATPS composed of polyethyleneglycol 3350 (PEG), potassium
      phosphate and sodium chloride, at pH 6.1, was evaluated and subjected to 50-fold
      scale-up (1 L). Further purification of the fractions was performed using
      caprylic acid precipitation and ion exchange chromatography. Similar yield and
      purity were obtained at both small and large scales. IgG precipitated in the PEG
      rich upper phase at 83% recovery and 2.75-fold purification factor. An 81% pure
      albumin fraction was obtained in the salt rich bottom phase with a 91% yield.
      After polishing, IgG was obtained at a recovery of 70% and a purity of 92%.
      Corresponding values for albumin were 91% and 90%. This IgG and albumin
      fractionation technology deserves further evaluation as it may represent a
      potential alternative to conventional plasma fractionation methods.

PMID- 22619189
TI  - Some thoughts from NICE.

PMID- 22619190
TI  - Positive leadership is key.

PMID- 22619191
TI  - Please drop this slur journalism.

PMID- 22619192
TI  - Bisphosphonates in the treatment of osteoporosis.

PMID- 22619193
TI  - Ultrasound guided corticosteroid injection for plantar fasciitis: randomised
      controlled trial.
AB  - OBJECTIVE: To investigate the effectiveness of ultrasound guided corticosteroid
      injection in the treatment of plantar fasciitis. DESIGN: Randomised, investigator
      and participant blinded, placebo controlled trial. SETTING: University clinic in
      Melbourne, Australia. PARTICIPANTS: 82 people with a clinical and ultrasound
      diagnosis of plantar fasciitis unrelated to systemic inflammatory disease.
      INTERVENTIONS: Participants were randomly allocated to ultrasound guided
      injection of the plantar fascia with either 1 mL of 4 mg/mL dexamethasone sodium
      phosphate (experimental group) or 1 mL normal saline (placebo). Before injection
      the participants were given an ultrasound guided posterior tibial nerve block
      with 2% lidocaine (lignocaine). MAIN OUTCOME MEASURES: Primary outcomes were
      pain, as measured by the foot health status questionnaire (0-100 point scale),
      and plantar fascia thickness, measured by ultrasound at 4, 8, and 12 weeks.
      RESULTS: Reduction in pain at four weeks favoured the dexamethasone group by 10.9
      points (95% confidence interval 1.4 to 20.4, P=0.03). Between group differences
      for pain scores at eight and 12 weeks were not statistically significant. Plantar
      fascia thickness measured at four weeks favoured the dexamethasone group by -0.35
      mm (95% confidence interval -0.67 to -0.03, P=0.03). At eight and 12 weeks,
      between group differences for plantar fascia thickness also favoured
      dexamethasone, at -0.39 mm (-0.73 to -0.05, P=0.02) and -0.43 mm (-0.85 to -0.01,
      P=0.04), respectively. The number needed to treat with dexamethasone for one
      successful outcome for pain at four weeks was 2.93 (95% confidence interval 2.76
      to 3.12). There were no reported adverse events associated with the intervention.
      CONCLUSION: A single ultrasound guided dexamethasone injection is a safe and
      effective short term treatment for plantar fasciitis. It provides greater pain
      relief than placebo at four weeks and reduces abnormal swelling of the plantar
      fascia for up to three months. However, clinicians offering this treatment should
      also note that significant pain relief did not continue beyond four weeks. TRIAL
      REGISTRATION: Australian New Zealand Clinical Trials Registry
      ACTRN12610000239066.

PMID- 22619194
TI  - Derivation and validation of updated QFracture algorithm to predict risk of
      osteoporotic fracture in primary care in the United Kingdom: prospective open
      cohort study.
AB  - OBJECTIVE: To develop and validate an updated version of the QFracture algorithm
      for estimating the risk of a patient sustaining an osteoporotic fracture or hip
      fracture in a primary care population. DESIGN: Prospective open cohort study
      using routinely collected data from 420 general practices in the United Kingdom
      to develop updated QFracture scores and 207 practices to validate scores. Cox's
      proportional hazards model was used in the derivation cohort to derive risk
      equations using several explanatory variables. We calculated measures of
      calibration and discrimination using the validation cohort. PARTICIPANTS:
      3,142,673 patients in derivation cohort and 1,583,373 in validation cohort, aged
      30-100 years, who contributed 23,608,337 and 11,732,106 person years of
      observation, respectively. We identified 59,772 incident diagnoses of
      osteoporotic fracture in the derivation cohort and 28,685 in the validation
      cohort. OUTCOMES: Incident diagnosis of osteoporotic fracture (vertebral, distal
      radius, proximal humerus, or hip) and incident hip fracture recorded in general
      practice records or linked cause of death records. RESULTS: We found significant
      independent associations with overall fracture risk in women for age, body mass
      index, ethnic origin, alcohol intake, smoking status, chronic obstructive
      pulmonary disease or asthma, any cancer, cardiovascular disease, dementia,
      diagnosis or treatment for epilepsy, history of falls, chronic liver disease,
      Parkinson's disease, rheumatoid arthritis or systemic lupus erythematosus,
      chronic renal disease, type 1 diabetes, type 2 diabetes, previous fracture,
      endocrine disorders, gastrointestinal malabsorption, any antidepressants,
      corticosteroids, unopposed hormone replacement therapy, and parental history of
      osteoporosis. Risk factors for hip fracture in women were similar except for
      gastrointestinal malabsorption and parental history of hip fracture. Risk factors
      for men were largely the same as those for women but also included care home
      residence. The updated hip fracture algorithm explained 71.7% (95% confidence
      interval 71.1% to 72.3%) of the variation in women and 70.4% (69.3% to 71.5%) in
      men. D statistic values for hip fracture were high for women (3.26, 3.21 to 3.31)
      and men (3.15, 3.06 to 3.24), and higher than for osteoporotic fracture. Values
      for the area under the receiver operating characteristics curves for hip fracture
      were 0.89 for women and 0.88 for men, compared with 0.79 and 0.71 for
      osteoporotic fracture, respectively. The updated algorithms performed better than
      the 2009 algorithms. CONCLUSIONS: Two QFracture algorithms were updated to
      predict risk of osteoporotic and hip fracture in primary care populations to
      include ethnic origin, all classes of antidepressants, chronic obstructive
      pulmonary disease, epilepsy, dementia, Parkinson's disease, cancer, systemic
      lupus erythematosus, chronic renal disease, type 1 diabetes, previous fragility
      fracture, and care home residence. These updated algorithms showed improved
      performance compared with previous QFracture algorithms reported in 2009.

PMID- 22619195
TI  - Politicians urge health department to consider over-ruling EU law to tackle drug
      shortages in UK.

PMID- 22619196
TI  - GPs spot two thirds of cancers at first presentation.

PMID- 22619197
TI  - Targeted referral takes time.

PMID- 22619198
TI  - Consider ketosis prone type 2 diabetes as cause of ketoacidosis in adult
      patients.

PMID- 22619199
TI  - Authors' reply to Litwin and Malhotra.

PMID- 22619200
TI  - The scientific community should lobby to be able to apply for drug licences.

PMID- 22619201
TI  - The benefits of early diagnosis of dementia.

PMID- 22619202
TI  - What about the sheer number of drugs prescribed?

PMID- 22619203
TI  - An equally hard thing: supporting the admission of error.

PMID- 22619204
TI  - Patients have the right to be informed about an error.

PMID- 22619205
TI  - Surgical management of appendicitis remains best option during pregnancy.

PMID- 22619206
TI  - Alzheimer's researchers face trial for scientific fraud and defrauding US
      government.

PMID- 22619207
TI  - Five years after baby Peter.

PMID- 22619208
TI  - Well-defined amphiphilic poly(2-oxazoline) ABA-triblock copolymers and their
      aggregation behavior in aqueous solution.
AB  - Self-organization of block copolymers in solution is a way to obtain advanced
      functional superstructures. The synthesis of well-defined polymethyloxazoline
      block-polyphenyloxazoline-block-polymethyloxazoline triblock copolymers is
      described and proven by (1) H NMR spectroscopy, SEC, and ESI-MS. The surprisingly
      water- soluble block copolymers do self-organize in aqueous solutions uniquely
      forming three coexisting well-defined structures: unimolecular micelles, micellar
      aggregates, and very form-stable polymersomes. This is the first example of a
      polymersome forming ABA-triblock copolymer with a glassy middle block. The
      spherical vesicles are analysed by scanning electron microscopy and transmission
      electron microscopy. It could be shown that these vesicles are indeed hollow
      spheres.

PMID- 22619210
TI  - M13 bacteriophage-activated superparamagnetic beads for affinity separation.
AB  - The growth of the biopharmaceutical industry has created a demand for new
      technologies for the purification of genetically engineered proteins.The
      efficiency of large-scale, high-gradient magnetic fishing could be improved if
      magnetic particles offering higher binding capacity and magnetization were
      available. This article describes several strategies for synthesizing microbeads
      that are composed of a M13 bacteriophage layer assembled on a superparamagnetic
      core. Chemical cross-linking of the pVIII proteins to a carboxyl-functionalized
      bead produces highly responsive superparamagnetic particles (SPM) with a side-on
      oriented, adherent virus monolayer. Also, the genetic manipulation of the pIII
      proteins with a His(6)  peptide sequence allows reversible assembly of the
      bacteriophage on a nitrilotriacetic-acid-functionalized core in an end-on
      configuration. These phage-magnetic particles are successfully used to separate
      antibodies from high-protein concentration solutions in a single step with a >90%
      purity. The dense magnetic core of these particles makes them five times more
      responsive to magnetic fields than commercial materials composed of polymer-(iron
      oxide) composites and a monolayer of phage could produce a 1000 fold higher
      antibody binding capacity. These new bionanomaterials appear to be well-suited to
      large-scale high-gradient magnetic fishing separation and promise to be cost
      effective as a result of the self-assembling and self-replicating properties of
      genetically engineered M13 bacteriophage.

PMID- 22619211
TI  - A mild one-step process from graphene oxide and Cd2+ to a graphene-CdSe quantum
      dot nanocomposite with enhanced photoelectric properties.
AB  - Good connections: A graphene-CdSe quantum dot (QD) nanocomposite is prepared
      through a one-step hydrothermal method using graphene oxide (GO),
      Cd(CH(3)COO)(2), Na(2) SeSO(3), and aminoethanethiol (AET). The bifunctional AET
      acts not only as a covalent linker but also as a reductant to transform GO into
      graphene. The photoactive graphene-QD nanocomposite exhibits a significantly
      higher photocurrent compared to the QDs, GO or the graphene substrate under
      illumination.

PMID- 22619212
TI  - Application of a 22L scale membrane bioreactor and cross-flow ultrafiltration to
      obtain purified chondroitin.
AB  - Recently, the possibility of producing fructosylated chondroitin from the
      capsular polysaccharide of Escherichia coli O5:K4:H4, in fed-batch and
      microfiltration experiments was assessed on a 2 L bioreactor. In this work, a
      first scale-up step was set on a 22 L membrane reactor with modified baffles to
      insert ad hoc designed microfiltration modules permanently inside the bioreactor
      vessel. Moreover, the downstream polysaccharide purification process, recently
      established on the A?KTA cross-flow instrument, was translated to a UNIFLUX-10, a
      tangential flow filtration system suitable for prepilot scale. In particular, the
      microfiltered permeates obtained throughout the fermentation, and the supernatant
      recovered from the centrifuged broth at the end of the process, were treated as
      two separate samples in the following ultrafiltration procedure, and the
      differences in the two streams and how these affected the
      ultrafiltration/diafiltration process performance were analysed. The total amount
      of K4 capsular polysaccharide was about 85% in the broth and 15% in the
      microfiltered permeates. However, the downstream treatment was more efficient
      when applied to the latter. The major contaminant, the lipopolysaccharide, could
      easily be separated by a mild hydrolysis that also results in the elimination of
      the unwanted fructosyl residue, which is linked to the C-3 of glucuronic acid
      residues. The tangential ultrafiltration/diafiltration protocols developed in a
      previous work were effectively scaled-up, and therefore in this research proof of
      principle was established for the biotechnological production of chondroitin from
      the wild-type strain E. coli O5:K4:H4. The complete downstream procedure yielded
      about 80% chondroitin with 90% purity.

PMID- 22619213
TI  - Studies on the solvation dynamics of coumarin 153 in 1-ethyl-3-methylimidazolium
      alkylsulfate ionic liquids: dependence on alkyl chain length.
AB  - Steady-state and time-resolved fluorescence behavior of coumarin 153 (C153) is
      investigated in a series of 1-ethyl-3-methylimidazolium alkylsulfate
      ([C(2)mim][C(n)OSO(3)]) ionic liquids differing only in the length of the linear
      alkyl chain (n = 4, 6, and 8) in the anion. The aim of the present study is to
      understand the role of alkyl chain length in solute rotation and solvation
      dynamics of C153 in these ionic liquids. The blueshift observed in the steady
      state absorption and emission maxima of C153 on going from the C(4)OSO(3) to the
      C(8)OSO(3) system indicates increasing nonpolar character of the microenvironment
      of the solute with increasing length of the alkyl side chain of the anion of the
      ionic liquids. The average solvation time is also found to increase on changing
      the substituent from butyl to octyl, and this is attributed to the increase in
      the bulk viscosity of the ILs. A steady blueshift of the time-zero maximum of the
      fluorescence spectrum with increasing alkyl chain length also indicates that the
      probe molecule experiences a less polar environment in the early part of the
      dynamics. Rotational dynamics of C153 are also analyzed by using the Stokes
      Einstein-Debye (SED), Gierer-Wirtz (GW), and Dote-Kivelson-Schwartz (DKS)
      theories. Analyses of the results seem to suggest decoupling of the rotational
      motion of the probe from solvent viscosity.

PMID- 22619214
TI  - DNA photocleavage by a cationic BODIPY dye through both singlet oxygen and
      hydroxyl radical: new insight into the photodynamic mechanism of BODIPYs.
AB  - Two new NIR-absorbing BODIPY dyes, each bearing two pyridinium groups, are
      synthesized and their DNA-binding affinities and DNA photocleavage abilities
      examined in depth. While one BODIPY dye photocleaves DNA mainly through singlet
      oxygen, the other photocleaves DNA through both singlet oxygen and hydroxyl
      radical. To the best of our knowledge, this is the first example of a hydroxyl
      radical being involved in the photodynamic behavior of BODIPY-type dyes. EPR
      experiments confirm the ability of these and several related BODIPYs to generate
      superoxide anion radical and hydroxyl radical. This finding may shed light on the
      mechanism of BODIPY-based photodynamic therapy (PDT) and open a new avenue for
      development of more efficient BODIPY-type PDT agents.

PMID- 22619215
TI  - Passport to clean competition.

PMID- 22619216
TI  - Testing athletes, and banning those who take drugs, is unjustifiable.

PMID- 22619217
TI  - Clear winners and losers are created by age only NHS resource allocation.

PMID- 22619218
TI  - A novel FADS1 isoform potentiates FADS2-mediated production of eicosanoid
      precursor fatty acids.
AB  - The fatty acid desaturase (FADS) genes code for the rate-limiting enzymes
      required for the biosynthesis of long-chain polyunsaturated fatty acids (LCPUFA).
      Here we report discovery and function of a novel FADS1 splice variant. FADS1
      alternative transcript 1 (FADS1AT1) enhances desaturation of FADS2, leading to
      increased production of eicosanoid precursors, the first case of an isoform
      modulating the enzymatic activity encoded by another gene. Multiple protein
      isoforms were detected in primate liver, thymus, and brain. In human neuronal
      cells, their expression patterns are modulated by differentiation and result in
      alteration of cellular fatty acids. FADS1, but not FADS1AT1, localizes to
      endoplasmic reticulum and mitochondria. Ribosomal footprinting demonstrates that
      all three FADS genes are translated at similar levels. The noncatalytic
      regulation of FADS2 desaturation by FADS1AT1 is a novel, plausible mechanism by
      which several phylogenetically conserved FADS isoforms may regulate LCPUFA
      biosynthesis in a manner specific to tissue, organelle, and developmental stage.

PMID- 22619220
TI  - Lagos state doctors are sacked for striking over pay.

PMID- 22619221
TI  - Full results on risks of epoetin emerge 14 years after major dialysis study.

PMID- 22619222
TI  - Vaccines are essential in campaigns against HIV and TB, say researchers.

PMID- 22619219
TI  - Role of sulfatide in normal and pathological cells and tissues.
AB  - Sulfatide is 3-O-sulfogalactosylceramide that is synthesized by two transferases
      (ceramide galactosyltransferase and cerebroside sulfotransferase) from ceramide
      and is specifically degraded by a sulfatase (arylsulfatase A). Sulfatide is a
      multifunctional molecule for various biological fields including the nervous
      system, insulin secretion, immune system, hemostasis/thrombosis, bacterial
      infection, and virus infection. Therefore, abnormal metabolism or expression
      change of sulfatide could cause various diseases. Here, we discuss the important
      biological roles of sulfatide in the nervous system, insulin secretion, immune
      system, hemostasis/thrombosis, cancer, and microbial infections including human
      immunodeficiency virus and influenza A virus. Our review will be helpful to
      achieve a comprehensive understanding of sulfatide, which serves as a fundamental
      target of prevention of and therapy for nervous disorders, diabetes mellitus,
      immunological diseases, cancer, and infectious diseases.

PMID- 22619223
TI  - Anonymised data of all NHS treatments must be put in public domain by 2015,
      strategy says.

PMID- 22619224
TI  - Autologous hematopoietic stem cell transplantation for multiple sclerosis--if
      confused or hesitant, remember: 'treat with standard immune suppressive drugs and
      if no inflammation, no response'.

PMID- 22619225
TI  - We are about to cure multiple sclerosis in the next 10 years, even though we do
      not know its cause: yes.
AB  - Proposal Never underestimate the pervasive, powerful influence of constructive
      chaos in medical progress.

PMID- 22619226
TI  - We are about to cure MS in the next 10 years, even though we do not know its
      cause: no.

PMID- 22619227
TI  - We are about to cure MS in the next 10 years, even though we do not know its
      cause: commentary.

PMID- 22619229
TI  - Redox implications of AMPK-mediated signal transduction beyond energetic clues.
AB  - Since the discovery of AMP-dependent protein kinase (AMPK), its fundamental role
      in regulating metabolic pathways and the molecular mechanism underlying the
      regulation of its activity by adenine nucleotides has been widely studied. AMPK
      is not only an energy-responsive enzyme, but it also senses redox signals. This
      review aims at recapitulating the recent lines of evidence that demonstrate the
      responsiveness of this kinase to metabolic and nitroxidative imbalance, thus
      providing new insights into the intimate networks of redox-based signals upstream
      of AMPK. In particular, we discuss its well-recognized activation downstream of
      mitochondrial dysfunction, debate the recent findings that AMPK is directly
      targeted by pro-oxidant species, and question alternative redox pathways that
      allow AMPK to be included into the large class of redox-sensing proteins. The
      possible therapeutic implications of the role of AMPK in redox-associated
      pathologies, such as cancer and neurodegeneration, are also discussed in light of
      recent advances that suggest a role for AMPK in the tuning of redox-dependent
      processes, such as apoptosis and autophagy.

PMID- 22619230
TI  - Plans to reform medical education and training are "worryingly opaque" and
      sluggish, warn MPs.

PMID- 22619231
TI  - Number of patients acquiring infections in hospitals falls by a fifth in five
      years.

PMID- 22619228
TI  - The axonal transport of mitochondria.
AB  - Vigorous transport of cytoplasmic components along axons over substantial
      distances is crucial for the maintenance of neuron structure and function. The
      transport of mitochondria, which serves to distribute mitochondrial functions in
      a dynamic and non-uniform fashion, has attracted special interest in recent years
      following the discovery of functional connections among microtubules, motor
      proteins and mitochondria, and their influences on neurodegenerative diseases.
      Although the motor proteins that drive mitochondrial movement are now well
      characterized, the mechanisms by which anterograde and retrograde movement are
      coordinated with one another and with stationary axonal mitochondria are not yet
      understood. In this Commentary, we review why mitochondria move and how they
      move, focusing particularly on recent studies of transport regulation, which
      implicate control of motor activity by specific cell-signaling pathways,
      regulation of motor access to transport tracks and static microtubule
      mitochondrion linkers. A detailed mechanism for modulating anterograde
      mitochondrial transport has been identified that involves Miro, a mitochondrial
      Ca(2+)-binding GTPase, which with associated proteins, can bind and control
      kinesin-1. Elements of the Miro complex also have important roles in
      mitochondrial fission-fusion dynamics, highlighting questions about the
      interdependence of biogenesis, transport, dynamics, maintenance and degradation.

PMID- 22619232
TI  - Melatonin inhibits IL1beta-induced MMP9 expression and activity in human
      umbilical vein endothelial cells by suppressing NF-kappaB activation.
AB  - Matrix metalloproteinases (MMPs) have been involved in inflammatory and
      degradative processes in pathologic conditions. The purpose of this study was to
      investigate the protective effect of melatonin in human umbilical vein
      endothelial cell (HUVEC) monolayer permeability and the regulation of MMP9
      induced by interleukin 1beta (IL1beta (IL1B)) in HUVECs. Protection studies were
      carried out with melatonin, a well-known antioxidant and antiinflammatory
      molecule. MMP9 expression was increased with IL1beta induction in HUVECs.
      Melatonin showed a barrier-protective role by downregulation of MMP9 and
      upregulation of tissue inhibitor of metalloproteinase-1 expression in HUVECs.
      Meanwhile, melatonin also decreased sodium fluorescein permeability and
      counteracted the downregulation of vascular endothelial cadherin and occludin
      expression in HUVECs. During inflammatory stimulus, nuclear factor-kappaB (NF
      kappaB) plays a significant role in regulating MMP genes expression, thus the
      function of NF-kappaB in HUVECs' barrier disruption was investigated. IL1beta
      induced nuclear translocation of NF-kappaB in HUVECs and regulated MMP9
      expression. However, NF-kappaB translocation into the nucleus was inhibited
      significantly by melatonin. Our results show that melatonin decreases the
      permeability of monolayer endothelial cell induced by IL1beta. At the same time,
      melatonin decreased the expression and activity of MMP9 by a NF-kappaB-dependent
      pathway in HUVECs induced by IL1beta.

PMID- 22619233
TI  - The effects of high fat diet on the basal activity of the hypothalamus-pituitary
      adrenal axis in mice.
AB  - Alterations in hypothalamus-pituitary-adrenal (HPA) axis activity have been
      linked to the development of the metabolic syndrome (MetS). Common features of
      the MetS, like insulin resistance and obesity, are reproducibly induced by high
      fat diet (HFD) in animal models of diet-induced obesity. These models, hampered
      by methodological differences, reveal conflicting results with respect to HPA
      axis activation. This study was aimed to evaluate in detail nonstressed diurnal
      HPA axis activity in mice during obesity development. Male C57Bl/6J mice were fed
      high or low fat diet for 12 weeks. HPA axis activity was evaluated by plasma
      corticosterone concentrations (at 0700, 1200, and 1800  h), corticotropin
      releasing hormone (CRH), and glucocorticoid receptor (GR) mRNA expression in the
      hippocampus, amygdala, and hypothalamus, and 11beta-hydroxysteroid dehydrogenase
      type-1 and -2 (11beta-HSD-1 and -2) expression in adipose tissue and liver.
      Within 1 week, the HFD induced obesity and decreased corticosterone levels at
      1200 and 1800  h, which persisted throughout the experiment. Twelve weeks of HFD
      decreased CRH mRNA in the paraventricular nucleus (PVN) and amygdala and GR mRNA
      in the PVN at 0900  h. At 1800  h, CRH mRNA expression increased in the PVN and
      amygdala, and GR mRNA increased in the CA1 region. 11beta-HSD-1 expressions
      decreased in gonadal, visceral, and subcutaneous adipose tissues at 0900 and 1800
      h, whereas hepatic 11beta-HSD-1 expression increased at 1800  h, whereas 11beta
      HSD-2 expression was unaffected. The HFD induces complex changes in the diurnal
      regulation of the different components of the HPA axis. These changes are not
      unequivocally characterized by increased, but rather by decreased HPA axis
      activity.

PMID- 22619234
TI  - Consequences of clinical situations that cause critical care nurses to experience
      moral distress.
AB  - Little is known about the consequences of moral distress. The purpose of this
      study was to identify clinical situations that caused nurses to experience moral
      distress, to understand the consequences of those situations, and to determine
      whether nurses would change their practice based on their experiences. The
      investigation used a descriptive approach. Open-ended surveys were distributed to
      a convenience sample of 204 critical care nurses employed at a university medical
      center. The analysis of participants' responses used an inductive approach and a
      thematic analysis. Each line of the data was reviewed and coded, and the codes
      were collapsed into themes. Methodological rigor was established. Forty-nine
      nurses responded to the survey. The majority of nurses had experienced moral
      distress, and the majority of situations that caused nurses to experience moral
      distress were related to end of life. The nurses described negative consequences
      for themselves, patients, and families.

PMID- 22619235
TI  - What actions promote a positive ethical climate? A critical incident study of
      nurses' perceptions.
AB  - Few qualitative studies explore the phenomenon of positive ethical climate and
      what actions are perceived as promoting it. Therefore, the aim of this study was
      to explore and describe actions that acute care ward nurses perceive as promoting
      a positive ethical climate. The critical incident technique was used. Interviews
      were conducted with 20 nurses at wards where the ethical climate was considered
      positive, according to a previous study. Meeting the needs of patients and next
      of kin in a considerate way, as well as receiving and giving support and
      information within the work group, promoted a positive ethical climate. Likewise,
      working as a team with a standard for behaviour within the work group promoted a
      positive ethical climate. Future research should investigate other conditions
      that might also promote a positive ethical climate.

PMID- 22619236
TI  - Nurses' perceptions of and responses to morally distressing situations.
AB  - Research on moral distress has paid limited attention to nurses' responses and
      actions. In a survey of nurses' perceptions of moral distress and ethical
      climate, 292 nurses answered three open-ended questions about situations that
      they considered morally distressing. Participants identified a range of
      situations as morally distressing, including witnessing unnecessary suffering,
      being forced to provide care that compromised values, and negative judgments
      about patients. They linked these situations to contextual constraints such as
      workload and described responses, including feeling incompetent and distancing
      themselves from patients. Participants described considerable effort to effect
      change, calling into question the utility of defining moral distress as an
      "inability to act due to institutional constraints" or a "failure to pursue a
      right course of action." Various understandings of moral distress operated, and
      action was integral to their responses. The findings suggest further conceptual
      work on moral distress and effort to support system-level change.

PMID- 22619237
TI  - Moral deliberation and nursing ethics cases: elements of a methodological
      proposal.
AB  - A qualitative study with an exploratory, descriptive and documentary design that
      was conducted with the objective of identifying the elements to constitute a
      method for the analysis of accusations of and proceedings for professional ethics
      infringements. The method is based on underlying elements identified inductively
      during analysis of professional ethics hearings judged by and filed in the
      archives of the Regional Nursing Board of Santa Catarina, Brazil, between 1999
      and 2007. The strategies developed were based on the results of an analysis of
      the findings of fact (occurrences/infractions, causes and outcomes) contained in
      the records of 128 professional ethics hearings and on the structural elements
      (statements, rules and practices) identified in five example professional ethics
      cases. The strategies suggested for evaluating accusations of ethics
      infringements and the procedures involved in deliberating on ethics hearings
      constitute a generic proposal that will require adaptation to the context of
      specific professional ethics accusations.

PMID- 22619238
TI  - Nurses' ethical conflict with hospitals: a longitudinal study of outcomes.
AB  - This study examined the association of nurses' ethical conflict with hospitals
      with organizational commitment, stress, turnover intention, absence and turnover.
      Participants were 410 nurses working at four different Canadian hospitals. A
      longitudinal design was used where nurses completed a questionnaire to capture
      ethical conflict, stress and organizational commitment, and one year later,
      measures of turnover intention, absence and actual turnover were obtained for the
      same sample. We found three aspects of nurses' ethical conflict with hospitals:
      patient care values, value of nurses, and staffing policy values. Our findings
      showed that all three aspects of nurses' ethical conflict are associated with
      stress and patient care values is associated with actual turnover. We also found
      that staffing policy values is predictive of turnover intention, and that patient
      care values is predictive of absenteeism. Thus, our findings show the
      multidimensionality of nurses' ethical conflict with hospitals. Further
      implications of our findings for practice and theory are discussed.

PMID- 22619239
TI  - Executive summary: 2012 Infectious Diseases Society of America clinical practice
      guideline for the diagnosis and treatment of diabetic foot infections.
AB  - Foot infections are a common and serious problem in persons with diabetes.
      Diabetic foot infections (DFIs) typically begin in a wound, most often a
      neuropathic ulceration. While all wounds are colonized with microorganisms, the
      presence of infection is defined by >=2 classic findings of inflammation or
      purulence. Infections are then classified into mild (superficial and limited in
      size and depth), moderate (deeper or more extensive), or severe (accompanied by
      systemic signs or metabolic perturbations). This classification system, along
      with a vascular assessment, helps determine which patients should be
      hospitalized, which may require special imaging procedures or surgical
      interventions, and which will require amputation. Most DFIs are polymicrobial,
      with aerobic gram-positive cocci (GPC), and especially staphylococci, the most
      common causative organisms. Aerobic gram-negative bacilli are frequently
      copathogens in infections that are chronic or follow antibiotic treatment, and
      obligate anaerobes may be copathogens in ischemic or necrotic wounds. Wounds
      without evidence of soft tissue or bone infection do not require antibiotic
      therapy. For infected wounds, obtain a post-debridement specimen (preferably of
      tissue) for aerobic and anaerobic culture. Empiric antibiotic therapy can be
      narrowly targeted at GPC in many acutely infected patients, but those at risk for
      infection with antibiotic-resistant organisms or with chronic, previously
      treated, or severe infections usually require broader spectrum regimens. Imaging
      is helpful in most DFIs; plain radiographs may be sufficient, but magnetic
      resonance imaging is far more sensitive and specific. Osteomyelitis occurs in
      many diabetic patients with a foot wound and can be difficult to diagnose
      (optimally defined by bone culture and histology) and treat (often requiring
      surgical debridement or resection, and/or prolonged antibiotic therapy). Most
      DFIs require some surgical intervention, ranging from minor (debridement) to
      major (resection, amputation). Wounds must also be properly dressed and off
      loaded of pressure, and patients need regular follow-up. An ischemic foot may
      require revascularization, and some nonresponding patients may benefit from
      selected adjunctive measures. Employing multidisciplinary foot teams improves
      outcomes. Clinicians and healthcare organizations should attempt to monitor, and
      thereby improve, their outcomes and processes in caring for DFIs.

PMID- 22619241
TI  - PHOTO QUIZ. A 12-month-old boy with pneumonia and hepatitis.

PMID- 22619242
TI  - 2012 Infectious Diseases Society of America clinical practice guideline for the
      diagnosis and treatment of diabetic foot infections.
AB  - Foot infections are a common and serious problem in persons with diabetes.
      Diabetic foot infections (DFIs) typically begin in a wound, most often a
      neuropathic ulceration. While all wounds are colonized with microorganisms, the
      presence of infection is defined by >=2 classic findings of inflammation or
      purulence. Infections are then classified into mild (superficial and limited in
      size and depth), moderate (deeper or more extensive), or severe (accompanied by
      systemic signs or metabolic perturbations). This classification system, along
      with a vascular assessment, helps determine which patients should be
      hospitalized, which may require special imaging procedures or surgical
      interventions, and which will require amputation. Most DFIs are polymicrobial,
      with aerobic gram-positive cocci (GPC), and especially staphylococci, the most
      common causative organisms. Aerobic gram-negative bacilli are frequently
      copathogens in infections that are chronic or follow antibiotic treatment, and
      obligate anaerobes may be copathogens in ischemic or necrotic wounds. Wounds
      without evidence of soft tissue or bone infection do not require antibiotic
      therapy. For infected wounds, obtain a post-debridement specimen (preferably of
      tissue) for aerobic and anaerobic culture. Empiric antibiotic therapy can be
      narrowly targeted at GPC in many acutely infected patients, but those at risk for
      infection with antibiotic-resistant organisms or with chronic, previously
      treated, or severe infections usually require broader spectrum regimens. Imaging
      is helpful in most DFIs; plain radiographs may be sufficient, but magnetic
      resonance imaging is far more sensitive and specific. Osteomyelitis occurs in
      many diabetic patients with a foot wound and can be difficult to diagnose
      (optimally defined by bone culture and histology) and treat (often requiring
      surgical debridement or resection, and/or prolonged antibiotic therapy). Most
      DFIs require some surgical intervention, ranging from minor (debridement) to
      major (resection, amputation). Wounds must also be properly dressed and off
      loaded of pressure, and patients need regular follow-up. An ischemic foot may
      require revascularization, and some nonresponding patients may benefit from
      selected adjunctive measures. Employing multidisciplinary foot teams improves
      outcomes. Clinicians and healthcare organizations should attempt to monitor, and
      thereby improve, their outcomes and processes in caring for DFIs.

PMID- 22619252
TI  - Copper is required for cobalt-induced transcriptional activity of hypoxia
      inducible factor-1.
AB  - Cobalt inhibits prolyl hydroxylases, leading to the accumulation of hypoxia
      inducible factor-1alpha (HIF-1alpha) and a concomitant increase in the
      transcriptional activity of HIF-1. Therefore, cobalt has been under development
      as a drug for activating HIF-1 under some disease conditions. However, it has
      been shown that ischemic conditions resulted in the loss of copper, and the
      activation of HIF-1 would not occur unless copper was supplemented. The present
      study was undertaken to test the hypothesis that copper is also required for the
      cobalt activation of HIF-1 transcriptional activity. Human umbilical vein
      endothelial cells subjected to treatment with cobalt chloride (CoCl(2)) at
      concentrations above 25 MUM for 2 h resulted in an accumulation of HIF-1alpha,
      which was determined by Western blot analysis, and an increase in the expression
      of vascular endothelial growth factor (VEGF), which was determined by real-time
      reverse transcription-polymerase chain reaction analysis for mRNA levels and
      enzyme-linked immunosorbent assay analysis for protein levels. The copper
      chelator tetraethylenepentamine at 25 MUM did not significantly affect the
      accumulation of HIF-1alpha but blocked increases in VEGF mRNA and protein levels,
      an effect that could be reversed by the addition of 25 MUM copper sulfate
      (CuSO(4)). In addition, gene silencing of the copper chaperone for Cu,Zn
      superoxide dismutase blocked VEGF expression with little effect on cobalt-induced
      HIF-1alpha accumulation. The present study thus demonstrates that copper was
      required for cobalt-activated transcriptional activity of HIF-1, although copper
      did not affect cobalt-induced accumulation of HIF-1alpha in the cells.

PMID- 22619251
TI  - Adenylyl cyclase 2 selectively couples to E prostanoid type 2 receptors, whereas
      adenylyl cyclase 3 is not receptor-regulated in airway smooth muscle.
AB  - Adenylyl cyclases (ACs) are important regulators of airway smooth muscle
      function, because beta-adrenergic receptor (betaAR) agonists stimulate AC
      activity and cAMP production. We have previously shown in a number of cell types
      that AC6 selectively couples to betaAR and these proteins are coexpressed in
      lipid rafts. We overexpressed AC2, AC3, and AC6 in mouse bronchial smooth muscle
      cells (mBSMCs) and human embryonic kidney (HEK)-293 cells by using recombinant
      adenoviruses and assessed their localization and regulation by various G protein
      coupled receptors (GPCRs). AC3 and AC6 were expressed primarily in caveolin-rich
      fractions, whereas AC2 expression was excluded from these domains. AC6 expression
      enhanced cAMP production in response to isoproterenol but did not increase
      responses to butaprost, reflecting the colocalization of AC6 with beta(2)AR but
      not E prostanoid type 2 receptor (EP(2)R) in lipid raft fractions. AC2 expression
      enhanced butaprost-stimulated cAMP production but had no effect on the beta(2)AR
      mediated response. AC3 did not couple to any GPCR tested. Forskolin-induced
      arborization of mBSMCs was assessed as a functional readout of cAMP signaling.
      Arborization was enhanced by overexpression of AC6 and AC3, but AC2 had no
      effect. GPCR-stimulated arborization mirrored the selective coupling observed for
      cAMP production. With the addition of the phosphodiesterase 4 (PDE4) inhibitor
      rolipram AC2 accelerated forskolin-stimulated arborization. Thus, AC2 selectively
      couples to EP(2)R, but signals from this complex are limited by PDE4 activity.
      AC3 does not seem to couple to GPCR in either mBSMCs or HEK-293 cells, so it
      probably exists in a distinct signaling domain in these cells.

PMID- 22619253
TI  - L-745,870 reduces L-DOPA-induced dyskinesia in the 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine-lesioned macaque model of Parkinson's disease.
AB  - L-DOPA-induced dyskinesia remains an unmet challenge in the treatment of
      Parkinson's disease (PD). Here, we investigate the potential antidyskinetic
      efficacy of 3-([4-(4-chlorophenyl)piperazin-1-yl]methyl)-1H-pyrrolo[2,3
      b]pyridine (L-745,870), a potent and selective dopamine D(4) receptor antagonist
      with a good toxicology profile and an excellent safety and tolerability record in
      phase I/II clinical studies, for non-PD indications. Six macaques were rendered
      parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration.
      After induction of stable and marked dyskinesia, animals were administered acute
      challenges of L-745,870 in combination with L-DOPA. To guarantee D(4) selectivity
      at the doses used in the study, we determined the plasma, cerebrospinal fluid,
      and brain levels of L-745,870. Coadministration of L-745,870 (1 mg/kg) and L-DOPA
      significantly reduced the severity of dyskinesia, by up to 59%, in comparison
      with L-DOPA alone (P < 0.01). L-745,870 had no effect on the duration of
      antiparkinsonian benefit (ON-time) (P > 0.05). However, L-745,870 (1 mg/kg)
      significantly increased the duration of ON-time without disabling dyskinesia
      (+204%; P < 0.001) and decreased duration of ON-time with disabling dyskinesia
      compared with L-DOPA alone (-56%; P < 0.01). Brain levels of L-745,870 (~600
      ng/g) were within the range at which L-745,870 provides selective D(4) receptor
      antagonism. Plasma levels were comparable with those demonstrated to be well
      tolerated in human studies. These data suggest that selective D(4) receptor
      antagonists represent a potential therapeutic approach for L-DOPA-induced
      dyskinesia. It is noteworthy that L-745,870 has already undergone significant
      clinical development, has an excellent profile for a therapeutic candidate, and
      could be advanced rapidly to phase IIa clinical studies for dyskinesia in PD.

PMID- 22619254
TI  - Estrogen provokes the depressant effect of chronic nicotine on vagally mediated
      reflex chronotropism in female rats.
AB  - We recently reported that acute nicotine impairs reflex tachycardic activity in
      estrogen-depleted, but not estrogen-repleted, female rats, suggesting a
      restraining influence for estrogen against the nicotine effect. In this study, we
      tested whether the baroreflex-protective effect of estrogen can be replicated
      when nicotine was administered chronically. We also report on the dose dependence
      and autonomic modulation of the nicotine-baroreflex interaction. The effects of
      nicotine (0.5, 1, or 2 mg/kg/day for 14 days) on baroreflex curves relating
      changes in heart rate to increases [phenylephrine (PE)] or decreases [sodium
      nitroprusside (SNP)] in blood pressure were evaluated in sham-operated (SO),
      ovariectomized (OVX), and estrogen-replaced OVX (OVXE(2)) rats. Slopes of the
      curves were taken as a measure of baroreflex sensitivity (BRS(PE) and BRS(SNP)).
      In SO rats, both reflex bradycardic and tachycardic responses were attenuated by
      nicotine in a dose-related fashion. In nicotine-treated rats, blockade of beta
      adrenergic (propranolol), but not muscarinic (atropine), receptors caused
      additional reductions in reflex chronotropic responses, implying that nicotine
      selectively impairs reflex vagal activity. OVX selectively decreased BRS(PE) but
      not BRS(SNP) and abolished the nicotine-induced impairment of either response.
      These effects of OVX were reversed after treatment with estrogen or the estrogen
      receptor modulator raloxifene. In atropine-treated rats, comparable BRS values
      were demonstrated in all rat preparations regardless of the estrogen or nicotine
      milieu. Collectively, the inhibition of vagal activity accounts for the
      depressant effect of chronic nicotine on baroreflex activity. Furthermore,
      contrary to nicotine's acute effects, the baroreflex-attenuating effect of
      chronic nicotine is exacerbated by estrogen.

PMID- 22619255
TI  - Kinematic analysis of motor recovery with human adult bone marrow-derived somatic
      cell therapy in a rat model of stroke.
AB  - BACKGROUND: The extent to which pharmaceutical and behavioral therapies following
      central nervous system injury may either deter or encourage the development of
      compensatory movement patterns is a topic of considerable interest in
      neurorehabilitation. However, functional outcome measures alone are relatively
      insensitive to compensatory changes in movement patterns per se. OBJECTIVE: This
      study used both functional outcome measures and kinematic analysis of forelimb
      movements to examine the effects of human adult bone marrow-derived somatic cells
      (hABM-SCs) on motor recovery in a rat model of stroke. METHODS: Adult male Long
      Evans black-hooded rats (n = 12) were trained in a forelimb reaching task and
      then underwent surgical middle cerebral artery occlusion, producing a stroke that
      impaired the trained paw. One week poststroke, animals were randomly assigned to
      either a hABM-SC injection or control injection group. Reaching behaviors were
      then compared at baseline and at 10 weeks poststroke. RESULTS: Both groups
      improved their outcome scores during the 10-week recovery period. However, the
      hABM-SC group recovered significantly more function than controls in terms of the
      number of pellets retrieved. Furthermore, the control group appeared to improve
      their functional performance by using compensatory strategies that involved an
      increased number of trajectory adjustments, whereas the hABM-SC group's
      kinematics more closely resembled prestroke movement patterns. CONCLUSIONS: This
      study demonstrates that kinematic measures established in stroke research on
      humans are also sensitive to performance differences prestroke versus poststroke
      in the rat model, reinforcing the utility of this method to evaluate treatments
      that may ultimately translate to patient populations.

PMID- 22619256
TI  - Voice quality after recurrent laryngeal nerve resection and immediate
      reconstruction.
AB  - OBJECTIVE: To evaluate clinician perception of voice quality, patient self
      reported psychosocial impact of dysphonia, and glottic closure in patients who
      have undergone resection of the recurrent laryngeal nerve (RLN) and immediate
      operative reconstruction during thyroid surgery. STUDY DESIGN: Prospective
      observational study. SETTING: Single tertiary care hospital. SUBJECTS AND
      METHODS: Nine patients underwent immediate operative reconstruction of the RLN by
      the senior author from 2002 to present. Outcome measures included (1) perceptual
      voice ratings assessed using the GRBAS (Grade, Roughness, Breathiness, Asthenia,
      Strain) scale, (2) psychosocial impact of dysphonia assessed using the Voice
      Handicap Index (VHI), and (3) assessment of glottic closure from laryngeal
      videostroboscopy. RESULTS: The RLN was reconstructed with primary anastomosis
      (4), free nerve graft (3), or vagus-RLN anastomosis (2). Seven patients had voice
      samples and videostroboscopy examinations obtained at a minimum of 9 months from
      surgery. Six were judged to have slight disturbance of voice based on overall
      Grade scoring (G = 1). Five rated their voice as normal or mild on the VHI
      instrument (score range 8-29). Laryngeal analysis revealed the immobile vocal
      fold in the median, physiologic phonating position with preserved bulk, recovered
      tension, and glottic closure during phonation. Three patients less than 9 months
      from surgery had an expected severe self-reported rating of dysphonia.
      CONCLUSION: Primary anastomosis, free nerve grafting, and vagus-RLN anastomosis
      are viable options for RLN reconstruction. Patients who undergo resection and
      immediate reconstruction of the RLN are able to regain self-perceived functional
      voices.

PMID- 22619257
TI  - Prevalence of jugular bulb abnormalities and resultant inner ear dehiscence: a
      histopathologic and radiologic study.
AB  - OBJECTIVE: Jugular bulb abnormalities (JBA), including high-riding jugular bulb
      (HRJB) and jugular bulb diverticulum (JBD), can erode into the inner ear. In this
      study, the authors investigate the prevalence and consequences of JBA and their
      erosion into inner ear structures using temporal bone histopathology and computed
      tomography (CT). STUDY DESIGN: Cross-sectional study of temporal bone
      histopathology and radiology. SETTING: Academic medical center. SUBJECTS AND
      METHODS: In total, 1579 temporal bone specimens and 100 CT of the temporal bones
      (200 ears) were examined for JBA and any associated dehiscence of inner ear
      structures. Temporal bone specimens were examined for histological consequences
      of inner ear erosion. Jugular bulb dimensions were measured on axial CT scans and
      compared across groups. Accompanying demographic and clinical information were
      reviewed. RESULTS: High jugular bulbs were noted in 8.2% (130/1579) of temporal
      bone specimens and in 8.5% (17/200) of temporal bone CT. The prevalence of JBA
      increases during the first 4 decades of life and stabilizes thereafter. High
      riding jugular bulbs eroded inner ear structures such as the vestibular aqueduct,
      vertical facial nerve, or posterior semicircular canal in 2.8% (44/1579) of cases
      histologically and 1.5% (3/200) radiologically. In most, jugular bulb-mediated
      inner ear dehiscence was clinically and radiologically silent. CONCLUSION:
      Jugular bulb abnormalities are common. They are present in 10% to 15% individuals
      and are primarily acquired by the fourth decade of life. In 1% to 3% of cases,
      the HRJB erodes into the inner ear and most frequently involves the vestibular
      aqueduct.

PMID- 22619258
TI  - Do pharmacokinetics explain persistent restenosis inhibition by a single dose of
      paclitaxel?
AB  - BACKGROUND: The purpose of this study was to investigate the elimination of
      paclitaxel from the arterial wall after a single short administration with a
      coated balloon. METHODS AND RESULTS: Slightly oversized paclitaxel-coated
      balloons (dose 3 or 9 MUg/mm(2)) without or with premounted stents were inflated
      in nonatherosclerotic coronary arteries of either young domestic pigs or adult
      Goettingen minipigs. The paclitaxel content of plasma, arterial segments, and
      residual hearts (without treated arteries) was measured for up to 180 days using
      high-performance liquid chromatography/ultraviolet detection or mass
      spectrometry. Angiograms were evaluated for lumen narrowing. The paclitaxel
      concentration in plasma remained <10 ng/mL. In arteries of domestic pigs and
      minipigs treated with paclitaxel-coated balloons with premounted stents, 10%+/-5%
      or 21%+/-8% of dose, respectively, was initially detected and decreased to 3.5%+/
      3.1% of dose (domestic pig) by Day 7. Within 6 months it fell with a half-life of
      1.9 months to 0.40%+/-0.35%. After 3 months the concentration in the arterial
      wall was 17+/-11 MUmol/L. Without a stent, drug transfer to the vessel wall was
      somewhat reduced and elimination faster. Immediately after treatment up to 26%+/
      4% of dose was detected in the residual whole hearts. It dropped with a half-life
      of 45 days to 1.5%+/-0.6% of dose (0.3 MUmol/L) within 6 months. CONCLUSIONS:
      After a single local administration with coated balloons, paclitaxel stays in the
      vessel wall of pigs long enough to explain persistent inhibition of neointimal
      proliferation. The pharmacokinetics of paclitaxel does, however, not exclude
      other reasons for sustained efficacy such as early blocking of processes
      initiating excessive and prolonged neointimal proliferation.

PMID- 22619259
TI  - Pharmacokinetic and pharmacodynamic effects of elinogrel: results of the platelet
      function substudy from the intravenous and oral administration of elinogrel to
      evaluate tolerability and efficacy in nonurgent percutaneous coronary
      intervention patients (INNOVATE-PCI) trial.
AB  - BACKGROUND: Elinogrel is the only selective, competitive and reversible platelet
      P2Y(12) inhibitor available in both intravenous (IV) and oral formulations.
      METHODS AND RESULTS: This substudy of the Intravenous and Oral Administration of
      Elinogrel to Evaluate Tolerability and Efficacy in Nonurgent Percutaneous
      Coronary Intervention patients (INNOVATE-PCI) trial evaluated the pharmacokinetic
      and pharmacodynamic effects of two dosing regimens of IV followed by oral
      elinogrel (120 mg IV plus 100 mg oral twice daily; 120 mg IV plus 150 mg oral
      twice daily) versus standard clopidogrel therapy (300-600 mg oral loading dose
      plus 75 mg oral maintenance dose) in 56 patients undergoing nonurgent PCI. At
      time of randomization, 71.4% (40/56) of patients were using maintenance
      clopidogrel therapy. In the acute phase, an IV bolus of elinogrel achieved more
      rapid and potent antiplatelet effects compared with clopidogrel, which were
      sustained during the transition from the IV to the oral formulation in the first
      24 hours of the peri-PCI period. During chronic therapy, elinogrel achieved
      similar levels of platelet reactivity compared with clopidogrel before the next
      oral dose and, although platelet reactivity was lower with elinogrel up to 6
      hours after daily oral maintenance dosing, these differences were not
      statistically significant. These pharmacodynamic effects matched the
      pharmacokinetic profile of elinogrel. There were no differences in
      pharmacodynamic and pharmacokinetic effects between the two elinogrel dosing
      regimens. CONCLUSIONS: Compared with clopidogrel, the combination of IV and oral
      elinogrel achieves more rapid and enhanced antiplatelet effects that were
      sustained through the transition to oral elinogrel in the peri-PCI period, but
      these were not significant during chronic dosing in this pilot investigation.
      CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT00751231.

PMID- 22619260
TI  - Duration of dual antiplatelet therapy and long-term clinical outcome after
      coronary drug-eluting stent implantation: landmark analyses from the CREDO-Kyoto
      PCI/CABG Registry Cohort-2.
AB  - BACKGROUND: Optimal duration of dual antiplatelet therapy (DAPT) after drug
      eluting stent (DES) implantation has not been yet fully elucidated. METHODS AND
      RESULTS: We assessed the influence of prolonged thienopyridine therapy on
      clinical outcomes with landmark analysis at 4 and 13 months after DES
      implantation. Among 6802 patients with at least 1 DES implantation in the CREDO
      Kyoto Registry Cohort-2, 6309 patients (on thienopyridine, 5438 patients; off
      thienopyridine, 871 patients) and 5901 patients (on thienopyridine, 4098
      patients; off thienopyridine, 1803 patients) were eligible for the 4- and 13
      month landmark analyses, respectively. The majority of patients had stable
      coronary artery disease (73%) and received sirolimus-eluting stents (93%), and
      approximately 90% of thienopyridine was ticlopidine. Patients taking
      thienopyridine had more complex comorbidities and more complex lesion and
      procedural characteristics as compared with patients not taking thienopyridine.
      After adjusting for confounders, thienopyridine use was not associated with
      decreased risk for death/myocardial infarction/stroke (hazard ratio [HR], 1.13;
      95% confidence interval [CI], 0.89-1.43, P=0.32 in the 4-month landmark analysis;
      HR, 1.14; 95% CI, 0.90-1.45, P=0.29 in the 13-month landmark analysis,
      respectively), whereas the risk for GUSTO moderate/severe bleeding tended to be
      higher in patients taking thienopyridine (HR, 1.51; 95% CI, 1.00-2.23, P=0.049 in
      the 4-month landmark analysis; HR, 1.44; 95% CI, 0.99-2.09, P=0.057 in the 13
      month landmark analysis, respectively). CONCLUSIONS: Prolonged thienopyridine
      therapy beyond 4 and 13 months appeared not to be associated with reduction in
      ischemic events but to be associated with a trend toward increased bleeding.
      Optimal duration of DAPT after DES implantation might be shorter than the
      currently recommended 1-year interval.

PMID- 22619261
TI  - Extent of palliative care need in the acute hospital setting: a survey of two
      acute hospitals in the UK.
AB  - BACKGROUND: In common with international health policy, The End of Life Care
      Strategy for England has highlighted the delivery of high quality palliative care
      in the acute hospital setting as an area of priority. AIM: The aim of this study
      was to explore the extent of palliative care need in the acute hospital setting,
      and to explore agreement between different sources in the identification of
      patients with palliative care need. DESIGN: A cross-sectional survey of
      palliative care need was undertaken in two UK acute hospitals. Hospital case
      notes were examined for evidence of palliative care need according to Gold
      Standards Framework (GSF) prognostic indicator criteria. Medical and nursing
      staff were asked to identify patients with palliative care needs. Patients (or
      consultees) completed assessments of palliative care need. PARTICIPANTS: Of a
      total in-patient population of 1359, complete datasets were collected for 514
      patients/consultees. RESULTS: 36.0% of patients were identified as having
      palliative care needs according to GSF criteria. Medical staff identified 15.5%
      of patients as having palliative care needs, and nursing staff 17.4% of patients.
      Patient self-report data indicated that 83.2% of patients meeting GSF criteria
      had palliative care needs. CONCLUSION: The results reveal that according to the
      GSF prognostic guide, over a third of hospital in-patients meet the criteria for
      palliative care need. Consensus between medical staff, nursing staff and the GSF
      was poor regarding the identification of patients with palliative care needs.
      This has significant implications for patient care, and draws into question the
      utility of the GSF in the hospital setting.

PMID- 22619262
TI  - Correction.

PMID- 22619263
TI  - Testing the hypothesis that diphtheria-tetanus-pertussis vaccine has negative non
      specific and sex-differential effects on child survival in high-mortality
      countries.
AB  - BACKGROUND: Measles vaccines (MV) have sex-differential effects on mortality not
      explained by protection against measles infection. OBJECTIVE: The authors
      examined whether whole-cell diphtheria-tetanus-pertussis (DTP) vaccine has sex
      differential and non-specific effects. DATA SOURCES AND ELIGIBILITY: Following
      previous reviews and a new search, the effect of DTP on mortality up to the next
      vaccination was assessed in all studies where DTP was given after BCG or DTP was
      given after MV and there was prospective follow-up after ascertainment of
      vaccination status. SETTING: High-mortality countries in Africa and Asia.
      METHODS: The initial observation of negative effect of DTP generated six
      hypotheses, which were examined in all available studies and two randomised
      trials reducing the time of exposure to DTP. MAIN OUTCOME: Consistency between
      studies. RESULTS: In the first study, DTP had negative effects on survival in
      contrast to the beneficial effects of BCG and MV. This pattern was repeated in
      the six other studies available. Second, the two 'natural experiments' found
      significantly higher mortality for DTP-vaccinated compared with DTP-unvaccinated
      children. Third, the female-male mortality ratio was increased after DTP in all
      nine studies; in contrast, the ratio was decreased after BCG and MV in all
      studies. Fourth, the increased female mortality associated with high-titre
      measles vaccine was found only among children who had received DTP after high
      titre measles vaccine. Fifth, in six randomised trials of early MV, female but
      not male mortality was increased if DTP was likely to be given after MV. Sixth,
      the mortality rate declined markedly for girls but not for boys when DTP
      vaccinated children received MV. The authors reduced exposure to DTP as most
      recent vaccination by administering a live vaccine (MV and BCG) shortly after
      DTP. Both trials reduced child mortality. CONCLUSIONS: These observations are
      incompatible with DTP merely protecting against the targeted diseases. With herd
      immunity to whooping cough, DTP is associated with higher mortality for girls.
      Randomised studies of DTP are warranted to measure the true impact on survival.

PMID- 22619264
TI  - Trends in cardiovascular disease biomarkers and their socioeconomic patterning
      among adults in the Scottish population 1995 to 2009: cross-sectional surveys.
AB  - OBJECTIVES: To examine secular and socioeconomic changes in biological
      cardiovascular disease risk factor and biomarker prevalences in the Scottish
      population. This could contribute to an understanding of why the decline in
      coronary heart disease mortality in Scotland has recently stalled along with
      persistence of associated socioeconomic inequalities. DESIGN: Cross-sectional
      surveys. SETTING: Scotland. PARTICIPANTS: Scottish Health Surveys: 1995, 1998,
      2003, 2008 and 2009 (6190, 6656, 5497, 4202 and 4964 respondents, respectively,
      aged 25-64 years). PRIMARY OUTCOME MEASURES: Gender-stratified, age-standardised
      prevalences of obesity, hypertension, hypercholesterolaemia and low high-density
      lipoprotein cholesterol blood concentration as well as elevated fibrinogen and C
      reactive protein concentrations according to education and social class
      groupings. Inequalities were assessed using the slope index of inequality, and
      time trends were assessed using linear regression. RESULTS: The prevalence of
      obesity, including central obesity, increased between 1995 and 2009 among men and
      women, irrespective of socioeconomic position. In 2009, the prevalence of obesity
      (defined by body mass index) was 29.8% (95% CI 27.9% to 31.7%) for men and 28.2%
      (26.3% to 30.2%) for women. The proportion of individuals with hypertension
      remained relatively unchanged between 1995 and 2008/2009, while the prevalence of
      hypercholesterolaemia declined in men from 79.6% (78.1% to 81.1%) to 63.8% (59.9%
      to 67.8%) and in women from 74.1% (72.6% to 75.7%) to 66.3% (62.6% to 70.0%).
      Socioeconomic inequalities persisted over time among men and women for most of
      the biomarkers and were particularly striking for the anthropometric measures
      when stratified by education. CONCLUSIONS: If there are to be further declines in
      coronary heart disease mortality and reduction in associated inequalities, then
      there needs to be a favourable step change in the prevalence of cardiovascular
      disease risk factors. This may require radical population-wide interventions.

PMID- 22619265
TI  - Clinical influences on antibiotic prescribing decisions for lower respiratory
      tract infection: a nine country qualitative study of variation in care.
AB  - OBJECTIVES: There is variation in antibiotic prescribing for lower respiratory
      tract infections (LRTI) in primary care that does not benefit patients. This
      study aims to investigate clinicians' accounts of clinical influences on
      antibiotic prescribing decisions for LRTI to better understand variation and
      identify opportunities for improvement. DESIGN: Multi country qualitative
      interview study. Semi-structured interviews using open-ended questions and a
      patient scenario. Data were subjected to five-stage analytic framework approach
      (familiarisation, developing a thematic framework from the interview questions
      and emerging themes, indexing, charting and mapping to search for
      interpretations), with interviewers commenting on preliminary reports. SETTING:
      Primary care. PARTICIPANTS: 80 primary care clinicians randomly selected from
      primary care research networks based in nine European cities. RESULTS: Clinicians
      reported four main individual clinical factors that guided their antibiotic
      prescribing decision: auscultation, fever, discoloured sputum and breathlessness.
      These were considered alongside a general impression of the patient derived from
      building a picture of the illness course, using intuition and familiarity with
      the patient. Comorbidity and older age were considered main risk factors for poor
      outcomes. Clinical factors were similar across networks, apart from C reactive
      protein near patient testing in Tromso. Clinicians developed ways to handle
      diagnostic and management uncertainty through their own clinical routines.
      CONCLUSIONS: Clinicians emphasised the importance of auscultation, fever,
      discoloured sputum and breathlessness, general impression of the illness course,
      familiarity with the patient, comorbidity, and age in informing their antibiotic
      prescribing decisions for LRTI. As some of these factors may be overemphasised
      given the evolving evidence base, greater standardisation of assessment and
      integration of findings may help reduce unhelpful variation in management. Non
      clinical influences will also need to be addressed.

PMID- 22619266
TI  - A new user cohort study comparing the safety of long-acting inhaled
      bronchodilators in COPD.
AB  - OBJECTIVE: To investigate a possible increased risk observed in tiotropium
      clinical trials of stroke and other adverse events. DESIGN: New users of long
      acting anticholinergic therapy (tiotropium HandiHaler(r)) were compared with new
      users of long-acting beta-agonist (LABA) monotherapy, and propensity scores were
      used to control confounding. SETTING: UK healthcare system general practitioner
      electronic medical record database. PARTICIPANTS: 10 840 patients newly
      prescribed tiotropium (n=4767) or LABA (n=6073), at least 40 years old, and not
      having asthma as their only respiratory illness. PRIMARY AND SECONDARY OUTCOME
      MEASURES: Incidence rates of total stroke, myocardial infarction, angina and
      other adverse events. RESULTS: Tiotropium was associated with increased rates of
      stroke (HR=1.49, 95% CI 0.91 to 2.45), angina (HR=1.38, 95% CI 0.88 to 2.16) and
      myocardial infarction (HR=1.26, 95% CI 0.72 to 2.21). Groups had similar rates of
      chronic obstructive pulmonary disease exacerbation (HR=0.95, 95% CI 0.80 to 1.12)
      and pneumonia (HR=0.96, 95% CI 0.58 to 1.58). Tiotropium was associated with a
      lower rate of total mortality (HR=0.70, 95% CI 0.56 to 0.89) and asthma
      exacerbations (HR=0.46, 95% CI 0.36 to 0.57) than users of LABA. CONCLUSION:
      Small increased risks of serious ischaemic cardiovascular events have been
      reported with inhaled anticholinergic medication from randomised and
      nonrandomized studies of ipratropium, tiotropium HandiHaler(r) and tiotropium
      Respimat(r). Additional research is needed to understand the full extent of
      cardiovascular effects of inhaled anticholinergic medications and the patients
      who may be most susceptible.

PMID- 22619267
TI  - Are they half as strong as they used to be? An experiment testing whether age
      related social comparisons impair older people's hand grip strength and
      persistence.
AB  - OBJECTIVE: To assess how age-related social comparisons, which are likely to
      arise inadvertently or deliberately during assessments, may affect older people's
      performance on tests that are used to assess their needs and capability. DESIGN:
      The study randomly assigned participants to a comparison with younger people or a
      no comparison condition and assessed hand grip strength and persistence. Gender,
      education, type of residence, arthritis and age were also recorded. SETTING: Age
      UK centres and senior's lunches in the South of England. PARTICIPANTS: An
      opportunity sample of 56 adults, with a mean age of 82.25 years. MAIN OUTCOMES
      MEASURES: Hand grip strength measured using a manual hand dynamometer and
      persistence of grip measured using a stopwatch. RESULTS: Comparison caused
      significantly worse performance measured by both strength (comparison =6.85 kg,
      95% CI 4.19 kg to 9.5 kg, control group =11.07 kg, 95% CI 8.47 kg to 13.68 kg, OR
      =0.51, p=0.027) and persistence (comparison =8.36 s, 95% CI 5.44 s to 11.29 s;
      control group =12.57 s, 95% CI 9.7 s to 15.45 s, OR =0.49, p=0.045). These
      effects remained significant after accounting for differences in arthritis,
      gender, education and adjusting for population age norms. CONCLUSIONS: Due to the
      potential for age comparisons and negative stereotype activation during
      assessment of older people, such assessments may underestimate physical
      capability by up to 50%. Because age comparisons are endemic, this means that
      assessment tests may sometimes seriously underestimate older people's capacity
      and prognosis, which has implications for the way healthcare professionals treat
      them in terms of autonomy and dependency.

PMID- 22619268
TI  - Birth outcomes for African and Caribbean babies in England and Wales:
      retrospective analysis of routinely collected data.
AB  - OBJECTIVES: To compare mean birth weights, gestational ages and odds of preterm
      birth and low birth weight of live singleton babies of black African or Caribbean
      ethnicity born in 2005 or 2006 by mother's country of birth. DESIGN: Secondary
      analysis of data from linked birth registration and NHS Numbers for Babies data
      set. SETTING: Births to women in England and Wales in 2005 and 2006.
      PARTICIPANTS: Babies of African and Caribbean ethnicity born in England and Wales
      in 2005-2006, whose mothers were born in African and Caribbean countries or the
      UK. Birth outcomes for 51 599 singleton births were analysed. MAIN OUTCOME
      MEASURES: Gestational age and birth weight. RESULTS: Mothers born in Eastern or
      Northern Africa had babies at higher mean gestational ages (39.38 and 39.41
      weeks, respectively) and lower odds of preterm birth (OR=0.80 and 0.65,
      respectively) compared with 39.00 weeks for babies with mothers born in the UK.
      Babies of African ethnicity whose mothers were born in Middle or Western Africa
      had mean birth weights of 3327 and 3311 g, respectively. These were significantly
      higher than the mean birth weight of 3257 g for babies of the UK-born mothers.
      Their odds of low birth weight (OR=0.75 and 0.72, respectively) were
      significantly lower. Babies of Caribbean ethnicity whose mothers were born in the
      Caribbean had higher mean birth weight and lower odds of low birth weight than
      those whose mothers were born in the UK. CONCLUSIONS: The study shows that in
      babies of African and Caribbean ethnicity, rates of low birth weight and preterm
      birth varied by mothers' countries of birth. Ethnicity and country of birth are
      important factors associated with perinatal health, but assessing them singly can
      mask important heterogeneity in birth outcomes within categories particularly in
      relation to African ethnicity. These differences should be explored further.

PMID- 22619269
TI  - Relationship between years in the trade and the development of radiographic knee
      osteoarthritis and MRI-detected meniscal tears and bursitis in floor layers. A
      cross-sectional study of a historical cohort.
AB  - OBJECTIVES: An increased risk of developing knee disorders including radiographic
      knee osteoarthritis (OA) have been shown among workers with kneeling working
      demands. There may also be a dose-related association between duration of
      employment in occupations with kneeling work and development of radiographic knee
      OA and magnetic resonance imaging (MRI)-detected meniscal tears and bursitis.
      DESIGN: A cross-sectional study of a historical cohort. SETTING: Members of the
      trade unions for floor layers and graphic designers in Denmark. PARTICIPANTS: 92
      male floor layers and 49 graphic designers aged 36-70 years were randomly
      selected among participants from a clinical and radiographic study of 156 floor
      layers and 152 graphic designers. OUTCOME MEASURES: Radiographic tibiofemoral
      (TF) and patellofemoral (PF) knee-OA and MRI-detected meniscal tears and
      bursitis. Results were adjusted for age, earlier knee traumas, sports activities
      and body mass index in logistic regression models. Association between TF OA and
      years in the floor-laying trade was graphically examined by a restricted cubic
      spline with four knots. RESULTS: Increase in number of years with exposure to
      kneeling work is associated with radiographic TF knee OA with ORs 0.7, 95% CI
      0.07 to 4.42; OR 1.89, 95% CI 0.29 to 12.3; OR 4.82, 95% CI 1.38 to 17 for <20
      years, 20-30 years and >30 years of kneeling work, respectively. MRI-verified
      medial meniscal tears was increased among subjects with kneeling work with OR
      1.96, 95% CI 0.79 to 4.88 to OR 4.73, 95% CI 1.16 to 19.4 but was not associated
      with duration of employment. Periarticular bursitis was increased in subjects
      with <20 years of kneeling working activity. Lateral meniscal tears and PF knee
      OA were not associated with duration of kneeling working activity or with
      kneeling work in general. CONCLUSIONS: The findings suggest a dose-response
      relationship for radiographic TF knee OA in floor layers with a significant
      amount of kneeling work and an increase of MRI-verified medial meniscal tears
      among workers with kneeling work.

PMID- 22619270
TI  - The foot in multistage ultra-marathon runners: experience in a cohort study of 22
      participants of the Trans Europe Footrace Project with mobile MRI.
AB  - OBJECTIVES: 67 runners participated in the Trans Europe FootRace 2009 (TEFR09), a
      4487 km (2789 mi) multistage ultra-marathon covering the south of Europe (Bari,
      Italy) to the North Cape. Reports on ultra-marathons are lacking, but the
      literature reports overuse injuries in athletes, especially to the Achilles
      tendon (AT), ankle or hind foot. Bone oedema may be related to exposure and is
      present in fatigue fractures. Therefore, the aim of this study was to determine
      prospectively if sustained maximal load during an ultra-marathon leads to damage
      to the foot. DESIGN AND PARTICIPANTS: In a cohort study, repeated scanning of the
      22 athletes participating in the study was performed before and during
      (approximately every 1000 km) the race. Using the obtained fat saturated
      inversion recovery sequence, two experienced readers blinded to the clinical data
      rated the images regarding foot lesions. Statistical analysis included regression
      analysis and computation of the inter-rater reliability. SETTING: The TEFR09
      course. MRI scanning was performed according to prearranged schedules for every
      participant, using a mobile 1.5 Tesla MRI unit on a trailer following the race.
      PRIMARY OUTCOME MEASURES: MRI data such as AT diameter, bone or tendon lesions,
      subcutaneous, plantar fascia or intraosseous oedema. RESULTS: The 22 study
      participants did not differ significantly from the total of the 67 TEFR09 runners
      regarding height, weight and age. The AT diameter increased significantly from
      6.8 to 7.8 mm as did intraosseous signal, bone lesions and subcutaneous oedema.
      However, finishers differed only regarding plantar aponeurosis and subcutaneous
      oedema from participants aborting the TEFR09. Inter-rater reliability was 0.88
      0.98. CONCLUSION: Under the extreme stress of the TEFR09, an increase of the AT
      diameter as well as bone signal are thought to be adaptive since only
      subcutaneous oedema and plantar fascia oedema were related to abortion of the
      race. TRIAL REGISTRATION NUMBER: University of Ulm, Germany Ethics Committee
      Number 78/08-UBB/se.

PMID- 22619271
TI  - Do statins improve outcomes in patients with asthma on inhaled corticosteroid
      therapy? A retrospective cohort analysis.
AB  - OBJECTIVES: Animal studies and clinical trials have examined the potential
      benefits of statins in asthma management with contradictory results. The
      objective of this study was to determine if asthma patients on concurrent statins
      are less likely to have asthma-related hospitalisations. DESIGN: A retrospective
      cohort study using Mississippi Medicaid data for 2002-2004. PARTICIPANTS: Asthma
      patients >=18 years were identified using the ICD9 code 493.xx from 1 July 2002
      through 31 December 2003. The index date for an exposed subject was any date
      within the identification period, 180 days prior to which the subject had at
      least one inhaled corticosteroid prescription and at least an 80% adherence rate
      to statins. Asthma patients on inhaled corticosteroids, but not on statins, were
      selected as the unexposed population. The two groups were matched and followed
      for 1 year beginning the index date. MAIN OUTCOMES MEASURES: Patient outcomes in
      terms of hospitalisations and ER visits were compared using conditional logistic
      regression. RESULTS: After matching, there were 479 exposed subjects and 958
      corresponding unexposed subjects. The odds of asthma-related hospitalisation
      and/or emergency room (ER) visits for asthma patients on concurrent statins were
      almost half the odds for patients not on statins (OR=0.55; 95% CI (0.37 to 0.84);
      p=0.0059). Similarly, the odds of asthma-related ER visits were significantly
      lower for patients on statins (OR=0.48; 95% CI (0.28 to 0.82); p=0.0069).
      CONCLUSION: The findings suggest beneficial effects of statins in asthma
      management. Further prospective investigations are required to provide more
      conclusive evidence.

PMID- 22619272
TI  - Establishment of an animal model of extracorporeal membrane oxygenation in
      rabbits.
AB  - OBJECTIVE: This study was undertaken to establish an animal model of
      extracorporeal membrane oxygenation in rabbits. METHODS: Ten New Zealand white
      rabbits weighing 2573+/-330 g were used in this study. Extracorporeal membrane
      oxygenation was established in these animals through cannulation of the right
      carotid artery and jugular vein for arterial perfusion and venous return. The
      components of the perfusion circuit were specially designed. Arterial blood
      pressure was measured with a blood pressure meter through cannulation of the
      right femoral artery. The heart rate and blood gas parameters were also monitored
      by electrocardiography and a blood gas analyzer (Radiometer ABL800, Bronshoj,
      Denmark), respectively. RESULTS: The rabbit model of extracorporeal membrane
      oxygenation was established successfully. The hemodynamic and blood gas
      parameters were changed within an acceptable range during the extracorporeal
      membrane oxygenation process. The specially designed miniature membrane
      oxygenator was sufficient to meet the extracorporeal membrane oxygenation needs
      in this animal model. CONCLUSION: The rabbit model of extracorporeal membrane
      oxygenation established through right carotid artery and jugular vein cannulation
      is feasible, easily operated and economical. It is an ideal model for further
      research of the pathophysiology and organ protection offered through the
      application of extracorporeal membrane oxygenation.

PMID- 22619273
TI  - Accordion effect in a thin-strut coronary stent.
AB  - Longitudinal compression (accordion effect) of modern thinner-strut stents has
      been recently recognised. We report a typical case of longitudinal stent
      compression caused by a post-dilatation balloon.

PMID- 22619274
TI  - Systems of care for ST-segment-elevation myocardial infarction: a report From the
      American Heart Association's Mission: Lifeline.
AB  - BACKGROUND: National guidelines call for participation in systems to rapidly
      diagnose and treat ST-segment-elevation myocardial infarction (STEMI). In order
      to characterize currently implemented STEMI reperfusion systems and identify
      practices common to system organization, the American Heart Association surveyed
      existing systems throughout the United States. METHODS AND RESULTS: A STEMI
      system was defined as an integrated group of separate entities focused on
      reperfusion therapy for STEMI within a geographic region that included at least 1
      hospital that performs percutaneous coronary intervention and at least 1
      emergency medical service agency. Systems meeting this definition were invited to
      participate in a survey of 42 questions based on expert panel opinion and
      knowledge of existing systems. Data were collected through the American Heart
      Association Mission: Lifeline website. Between April 2008 and January 2010, 381
      unique systems involving 899 percutaneous coronary intervention hospitals in 47
      states responded to the survey, of which 255 systems (67%) involved urban
      regions. The predominant funding sources for STEMI systems were percutaneous
      coronary intervention hospitals (n = 320, 84%) and /or cardiology practices (n =
      88, 23%). Predominant system characteristics identified by the survey included:
      STEMI patient acceptance at percutaneous coronary intervention hospital
      regardless of bed availability (N = 346, 97%); single phone call activation of
      catheterization laboratory (N = 335, 92%); emergency department physician
      activation of laboratory without cardiology consultation (N = 318, 87%); data
      registry participation (N = 311, 84%); and prehospital activation of the
      laboratory through emergency department notification without cardiology
      notification (N = 297, 78%). The most common barriers to system implementation
      were hospital (n = 139, 37%) and cardiology group competition (n = 81, 21%) and
      emergency medical services transport and finances (n = 99, 26%). CONCLUSIONS:
      This survey broadly describes the organizational characteristics of collaborative
      efforts by hospitals and emergency medical services to provide timely reperfusion
      in the United States. These findings serve as a benchmark for existing systems
      and should help guide healthcare teams in the process of organizing care for
      patients with STEMI.

PMID- 22619275
TI  - Low-dose physical activity attenuates cardiovascular disease mortality in men and
      women with clustered metabolic risk factors.
AB  - BACKGROUND: Physical activity may ameliorate the health hazards of metabolic
      disorders but evidence is inconclusive, and estimates of the minimal threshold
      for protection remain unknown. METHODS AND RESULTS: The sample comprised 23 747
      men and women (aged 54.1 +/- 12.7 years [mean+/-SD], 45.2% men) without a known
      history of cardiovascular disease at baseline who were drawn from the Health
      Survey for England and the Scottish Health Survey. Based on blood pressure, high
      density lipoprotein cholesterol, diabetes, waist circumference, and low-grade
      inflammation (C-reactive protein >= 3 mg/L), participants were classified as
      metabolically healthy (zero or one metabolic abnormality) or unhealthy (>= 2
      metabolic abnormalities). Self-reported physical activity was assessed at
      baseline. Cox proportional hazards models were used to examine the association of
      clustered metabolic risk and physical activity with mortality, controlling for
      age, sex, smoking, socioeconomic group, cardiovascular disease medication, and
      self-rated health. Over 7.0 +/- 3.0 years follow-up, there were 2264 all-cause
      and 717 cardiovascular disease deaths, respectively. A physical activity
      threshold of at least one to 2 sessions per week was found to provide protection
      against mortality. Compared with active/metabolically healthy, the active with
      clustered metabolic abnormalities were not at elevated risk of cardiovascular
      disease (hazard ratio, 0.82; 95% CI, 0.54 -1.26) or all-cause mortality (hazard
      ratio, 1.11; 95% CI, 0.89 -1.39), although their inactive counterparts were at
      elevated risk of cardiovascular disease (hazard ratio, 1.41; 95% CI, 1.05 -1.91)
      and all-cause mortality (hazard ratio, 1.50; 95% CI, 1.27-1.78). CONCLUSIONS: The
      risk of cardiovascular disease associated with poor metabolic health is
      substantially lower among those who are physically active. At minimum, a weekly
      bout of moderate to vigorous physical activity is protective in men and women
      with clustered metabolic abnormalities.

PMID- 22619276
TI  - Interdependence theory and the actor-partner interdependence model: where theory
      and method converge.
AB  - This work describes an application of the actor-partner interdependence model
      (APIM) that allows researchers to test hypotheses in terms of interdependence
      theory (IT). The authors' goal is to move beyond the obvious similarities of
      these two frameworks by providing a detailed conceptual integration. This
      analysis demonstrates that aspects of APIM analysis reveal a useful perspective
      on interdependence not explicitly articulated by IT. They also expand on ideas
      presented by Kenny and Ledermann by exploring the relationship between their
      ratio parameter k and IT, and introducing two additional ratios (h and c) also
      suggested by IT. A complete worked example of APIM analysis from the perspective
      of IT, along with a SAS MACRO that produces confidence intervals for k, h, and c,
      is provided.

PMID- 22619277
TI  - Bayesian approach to non-inferiority trials for normal means.
AB  - Regulatory framework recommends that novel statistical methodology for analyzing
      trial results parallels the frequentist strategy, e.g. the new method must
      protect type-I error and arrive at a similar conclusion. Keeping these in mind,
      we construct a Bayesian approach for non-inferiority trials with normal response.
      A non-informative prior is assumed for the mean response of the experimental
      treatment and Jeffrey's prior for its corresponding variance when it is unknown.
      The posteriors of the mean response and variance of the treatment in historical
      trials are then assumed as priors for its corresponding parameters in the current
      trial, where that treatment serves as the active control. From these priors, a
      Bayesian decision criterion is derived to determine whether the experimental
      treatment is non-inferior to the active control. This criterion is evaluated and
      compared with the frequentist method using simulation studies. Results show that
      both Bayesian and frequentist approaches perform alike, but the Bayesian approach
      has a higher power when the variances are unknown. Both methods also arrive at
      the same conclusion of non-inferiority when applied on two real datasets. A major
      advantage of the proposed Bayesian approach lies in its ability to provide
      posterior probabilities for varying effect sizes of the experimental treatment
      over the active control. 

PMID- 22619278
TI  - Preservation of myocardial structure is enhanced by pim-1 engineering of bone
      marrow cells.
AB  - RATIONALE: Bone marrow-derived cells to treat myocardial injury improve cardiac
      function and support beneficial cardiac remodeling. However, survival of stem
      cells is limited due to low proliferation of transferred cells. OBJECTIVE: To
      demonstrate long-term potential of c-kit(+) bone marrow stem cells (BMCs)
      enhanced with Pim-1 kinase to promote positive cardiac remodeling. METHODS AND
      RESULTS: Lentiviral modification of c-kit(+) BMCs to express Pim-1 (BMCeP)
      increases proliferation and expression of prosurvival proteins relative to BMCs
      expressing green fluorescent protein (BMCe). Intramyocardial delivery of BMCeP at
      time of infarction supports improvements in anterior wall dimensions and prevents
      left ventricle dilation compared with hearts treated with vehicle alone.
      Reduction of the akinetic left ventricular wall was observed in BMCeP-treated
      hearts at 4 and 12 weeks after infarction. Early recovery of cardiac function in
      BMCeP-injected hearts facilitated modest improvements in hemodynamic function up
      to 12 weeks after infarction between cell-treated groups. Persistence of BMCeP is
      improved relative to BMCe within the infarct together with increased recruitment
      of endogenous c-kit(+) cells. Delivery of BMC populations promotes cellular
      hypertrophy in the border and infarcted regions coupled with an upregulation of
      hypertrophic genes. Thus, BMCeP treatment yields improved structural remodeling
      of infarcted myocardium compared with control BMCs. CONCLUSIONS: Genetic
      modification of BMCs with Pim-1 may serve as a therapeutic approach to promote
      recovery of myocardial structure. Future approaches may take advantage of
      salutary BMC actions in conjunction with other stem cell types to increase
      efficacy of cellular therapy and improve myocardial performance in the injured
      myocardium.

PMID- 22619280
TI  - Noise-free visualization of microscopic calcium signaling by pixel-wise fitting.
AB  - RATIONALE: Our insights into physiological and pathophysiological cardiac
      excitation-contraction coupling has greatly benefited from significant
      advancement in optical technologies such as high-speed confocal microscopy. This
      has pushed pixel dwell times into the time domain of nanoseconds, resulting in
      low signal-to-noise ratios, which have limited data analysis and interpretation.
      OBJECTIVE: Line scan imaging has been and still is dominant in high speed
      confocal recording. It allows analysis only of a small fraction of a cell's cross
      section (1.5%), but the appreciation of spatiotemporal fine details of excitation
      contraction coupling is instrumental for the further understanding of
      pathological mechanisms. We aim to provide a novel analysis tool to extract
      otherwise hidden fine details in cardiac excitation-contraction coupling from
      high-speed 2-dimensional confocal image series. METHODS AND RESULTS: We
      demonstrate that high-speed 2-dimensional confocal data (150 frames/s) can be
      analyzed quantitatively by a pixel-wise fitting approach, using a mathematical
      formalism to phenomenologically describe local calcium transients. Such an
      approach produces virtually noise-free fluorescence data originating from minute
      volumes (0.025 femtoliter) and allows extraction of detailed and most importantly
      quantitative and mechanistically novel information on microscopic calcium
      signaling and excitation-contraction coupling in a robust manner. CONCLUSIONS:
      Pixel-wise fitting provides novel insights into cardiac excitation-contraction
      coupling. Specifically, it revealed microscopic calcium alternans on the level of
      individual coupling sites. Microscopic calcium alternans is an early precursor of
      cellular alternans and as such will shed more light onto this mechanism leading
      to cardiac arrhythmia.

PMID- 22619279
TI  - Role of coronin 1B in PDGF-induced migration of vascular smooth muscle cells.
AB  - RATIONALE: The type I subclass of coronins, a family of actin-binding proteins,
      regulates various actin-dependent cellular processes, including migration.
      However, the existence and role of coronins in vascular smooth muscle cell (VSMC)
      migration has yet to be determined. OBJECTIVE: The goal of the present study was
      to define the mechanism by which coronins regulate platelet-derived growth factor
      (PDGF)-induced VSMC migration. METHODS AND RESULTS: Coronin 1B (Coro1B) and 1C
      (Coro1C) were both found to be expressed in VSMCs at the mRNA and protein levels.
      Downregulation of Coro1B by siRNA increases PDGF-induced migration, while
      downregulation of Coro1C has no effect. We confirmed through kymograph analysis
      that the Coro1B-downregulation-mediated increase in migration is directly linked
      to increased lamellipodial protraction rate and protrusion distance in VSMC. In
      other cell types, coronins exert their effects on lamellipodia dynamics by an
      inhibitory interaction with the ARP2/3 complex, which is disrupted by the
      phosphorylation of Coro1B. We found that PDGF induces phosphorylation of Coro1B
      on serine-2 via PKCepsilon, leading to a decrease in the interaction of Coro1B
      with the ARP2/3 complex. VSMCs transfected with a phosphodeficient S2A Coro1B
      mutant showed decreased migration in response to PDGF, suggesting that the
      phosphorylation of Coro1B is required for the promotion of migration by PDGF. In
      both the rat and mouse, Coro1B phosphorylation was increased in response to
      vessel injury in vivo. CONCLUSIONS: Our data suggest that phosphorylation of
      Coro1B and the subsequent reduced interaction with ARP2/3 complex participate in
      PDGF-induced VSMC migration, an important step in vascular lesion formation.

PMID- 22619281
TI  - Platelet function testing in patients with coronary artery disease: is the Who
      and the When any clearer than the What and the What then?

PMID- 22619282
TI  - A bridge far enough?

PMID- 22619283
TI  - Ideal cardiovascular health predicts lower risks of myocardial infarction,
      stroke, and vascular death across whites, blacks, and hispanics: the northern
      Manhattan study.
AB  - BACKGROUND: Evidence of the relationship of cardiovascular health (CVH), defined
      by the American Heart Association, and specific cardiovascular outcomes is
      lacking, particularly among Hispanics. This study sought to evaluate the
      relationship between the number of ideal CVH metrics and cardiovascular risk,
      overall and by event subtype, in a multiethnic community-based prospective
      cohort. METHODS AND RESULTS: A total of 2981 subjects (mean age, 69+/-10 years;
      54% Caribbean Hispanic, 25% black, 21% white) free of myocardial infarction and
      stroke at baseline in the Northern Manhattan Study were prospectively followed up
      (median follow-up, 11 years). The relationship between the number of ideal CVH
      metrics and the risk of cardiovascular disease, including myocardial infarction,
      stroke, and vascular death, was investigated. Overall, a strong gradient
      relationship was observed between the adjusted hazard ratios for cardiovascular
      disease and the number of ideal CVH metrics: 0.73 (95% confidence interval, 0.60
      0.89), 0.61 (95% confidence interval, 0.50-0.76), 0.49 (95% confidence interval,
      0.38-0.63), and 0.41 (95% confidence interval, 0.26-0.63) for those having 2, 3,
      4, and 5 to 6 ideal CVH metrics, respectively, compared with those having 0 to 1
      ideal CVH metrics (P for trend <0.0001). Similar graded relationships were found
      between the number of ideal CVH metrics and the adjusted incidence rate for each
      specific outcome and among whites, blacks, and Caribbean Hispanics. CONCLUSIONS:
      Our findings demonstrated a steep gradient relationship between ideal CVH and
      individual cardiovascular disease end points, including stroke, that was similar
      for whites, blacks, and Caribbean Hispanics. This evidence supports the
      application of the AHA ideal cardiovascular health metrics for cardiovascular
      disease risk assessment and health promotion for all Americans regardless of race
      ethnic background.

PMID- 22619285
TI  - Disparities in ideal cardiovascular health: a challenge or an opportunity?

PMID- 22619286
TI  - American diabetes association-European association for the study of diabetes
      position statement: due diligence was conducted.

PMID- 22619287
TI  - Optimizing care in diabetes: a quixotic challenge.

PMID- 22619284
TI  - Use of an intrapericardial, continuous-flow, centrifugal pump in patients
      awaiting heart transplantation.
AB  - BACKGROUND: Contemporary ventricular assist device therapy results in a high rate
      of successful heart transplantation but is associated with bleeding, infections,
      and other complications. Further reductions in pump size, centrifugal design, and
      intrapericardial positioning may reduce complications and improve outcomes.
      METHODS AND RESULTS: We studied a small, intrapericardially positioned,
      continuous-flow centrifugal pump in patients requiring an implanted ventricular
      assist device as a bridge to heart transplantation. The course of investigational
      pump recipients was compared with that of patients implanted contemporaneously
      with commercially available devices. The primary outcome, success, was defined as
      survival on the originally implanted device, transplantation, or explantation for
      ventricular recovery at 180 days and was evaluated for both noninferiority and
      superiority. Secondary outcomes included a comparison of survival between groups
      and functional and quality-of-life outcomes and adverse events in the
      investigational device group. A total of 140 patients received the
      investigational pump, and 499 patients received a commercially available pump
      implanted contemporaneously. Success occurred in 90.7% of investigational pump
      patients and 90.1% of controls, establishing the noninferiority of the
      investigational pump (P<0.001; 15% noninferiority margin). At 6 months, median 6
      minute walk distance improved by 128.5 m, and both disease-specific and global
      quality-of-life scores improved significantly. CONCLUSIONS: A small,
      intrapericardially positioned, continuous-flow, centrifugal pump was noninferior
      to contemporaneously implanted, commercially available ventricular assist
      devices. Functional capacity and quality of life improved markedly, and the
      adverse event profile was favorable. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00751972.

PMID- 22619288
TI  - Trends in death rates among U.S. adults with and without diabetes between 1997
      and 2006: findings from the National Health Interview Survey.
AB  - OBJECTIVE: To determine whether all-cause and cardiovascular disease (CVD) death
      rates declined between 1997 and 2006, a period of continued advances in treatment
      approaches and risk factor control, among U.S. adults with and without diabetes.
      RESEARCH DESIGN AND METHODS: We compared 3-year death rates of four consecutive
      nationally representative samples (1997-1998, 1999-2000, 2001-2002, and 2003
      2004) of U.S. adults aged 18 years and older using data from the National Health
      Interview Surveys linked to National Death Index. RESULTS: Among diabetic adults,
      the CVD death rate declined by 40% (95% CI 23-54) and all-cause mortality
      declined by 23% (10-35) between the earliest and latest samples. There was no
      difference in the rates of decline in mortality between diabetic men and women.
      The excess CVD mortality rate associated with diabetes (i.e., compared with
      nondiabetic adults) decreased by 60% (from 5.8 to 2.3 CVD deaths per 1,000) while
      the excess all-cause mortality rate declined by 44% (from 10.8 to 6.1 deaths per
      1,000). CONCLUSIONS: Death rates among both U.S. men and women with diabetes
      declined substantially between 1997 and 2006, reducing the absolute difference
      between adults with and without diabetes. These encouraging findings, however,
      suggest that diabetes prevalence is likely to rise in the future if diabetes
      incidence is not curtailed.

PMID- 22619289
TI  - The American Diabetes Association diabetes research perspective.

PMID- 22619290
TI  - Peroxisome proliferator-activated receptor gamma polymorphism Pro12Ala Is
      associated with nephropathy in type 2 diabetes: evidence from meta-analysis of 18
      studies.
AB  - OBJECTIVE: Insulin resistance plays a part in diabetic nephropathy (DN). The
      association between the peroxisome proliferator-activated receptor gamma Pro to
      Ala alteration at codon 12 (Pro12Ala) polymorphism and the risk of insulin
      resistance has been confirmed. The association between the polymorphism and DN
      risk has also been widely studied recently, but no consensus was available up to
      now. RESEARCH DESIGN AND METHODS: A systematic search of electronic databases
      (MEDLINE, Embase, and China National Knowledge Infrastructure) and reference
      lists of relevant articles was carried out, and then 18 case-control studies
      involving 3,361 DN cases and 5,825 control subjects were identified. RESULTS: In
      the overall analysis, the Ala12 variant was observed to be significantly
      associated with decreased DN risk (odds ratio 0.76 [95% CI 0.61-0.93]). Some
      evidence of heterogeneity among the included studies was detected, which could be
      explained by the difference of ethnicity and stage of DN. Subgroup analyses
      stratified by ethnicity and stage of DN were performed, and results indicated the
      Pro12Ala polymorphism was associated with the risk of DN in Caucasians but no
      similar association was observed in Asians. Additionally, we observed that Ala12
      was associated with decreased risk of albuminuria. With only a few of subjects
      were available, we failed to detect statistically significant association between
      the polymorphism and end-stage renal disease (ESRD). CONCLUSIONS: Our results
      indicated that the Ala12 variant is a significantly protective factor for DN.
      Future research should focus on the effect of Pro12Ala polymorphism on ESRD and
      gathering data of Africans.

PMID- 22619292
TI  - Sulfonylurea use during entire pregnancy in diabetes because of KCNJ11 mutation:
      a report of two cases.

PMID- 22619293
TI  - Successful use of omalizumab in an inadequately controlled type 2 diabetic
      patient with severe insulin allergy.

PMID- 22619294
TI  - Comment on: Hegde et al. effect of 3-month yoga on oxidative stress in type 2
      diabetes with or without complications: a controlled clinical trial. Diabetes
      Care 2011;34: 2208-2210.

PMID- 22619296
TI  - Comment on: Leeds et al. high prevalence of microvascular complications in adults
      with type 1 diabetes and newly diagnosed celiac disease. Diabetes Care
      2011;34:2158-2163.

PMID- 22619297
TI  - Comment on: Kromhout et al. n-3 fatty acids, ventricular arrhythmia-related
      events, and fatal myocardial infarction in postmyocardial infarction patients
      with diabetes. Diabetes Care 2011;34:2515-2520.

PMID- 22619299
TI  - Comment on: Ellervik et al. elevated transferrin saturation and risk of diabetes:
      three population-based studies. Diabetes Care 2011;34:2256-2258.

PMID- 22619301
TI  - Comment on: Calleja et al. insulin resistance is associated with a poor response
      to intravenous thrombolysis in acute ischemic stroke. Diabetes Care 2011;34:2413
      2417.

PMID- 22619303
TI  - Comment on: Wheeler et al. macronutrients, food groups, and eating patterns in
      the management of diabetes: a systematic review of the literature, 2010. Diabetes
      Care 2012;35:434-445.

PMID- 22619305
TI  - Molecular pathways: involving microenvironment damage responses in cancer therapy
      resistance.
AB  - The armamentarium of therapeutics used to treat cancer patients relies heavily on
      ionizing radiation and chemotherapeutic drugs that severely damage DNA. Tumor
      cells' responses to such treatments are heavily influenced by their environment:
      Physical contacts with structural elements such as the extracellular matrix,
      associations with resident and transitory benign cells such as fibroblasts and
      leukocytes, and interactions with numerous soluble endocrine and paracrine-acting
      factors all modulate tumor-cell behavior. Of importance, this complex tumor
      microenvironment is not static and dynamically responds to a variety of stimuli.
      Here, we describe emerging data indicating that genotoxic cancer treatments
      activate highly conserved damage response programs in benign constituents of the
      tumor microenvironment. These damage signals, transmitted via master regulators
      such as NF-kappaB, culminate in a powerful and diverse secretory program that
      generates a proangiogenic, proinflammatory microenvironment. Constituents of this
      program include interleukin (IL)-6, IL-8, hepatocyte growth factor, amphiregulin,
      matrix metalloproteinases, and other factors that have been shown to promote
      adverse tumor-cell phenotypes, such as enhanced resistance to treatment and rapid
      tumor repopulation. A detailed understanding of these survival signals induced in
      the context of genotoxic stress provides a platform for developing combinatorial
      treatment strategies that take into account malignant cells, the tumor
      microenvironment, and the dynamics exerted by the treatment itself.

PMID- 22619306
TI  - Anti-myeloma effects of the novel anthracycline derivative INNO-206.
AB  - PURPOSE: Doxorubicin has shown efficacy especially in combination treatment for
      the treatment of multiple myeloma; however, its side effects limit its use. INNO
      206 is an albumin-binding prodrug of doxorubicin, which is released from albumin
      under acidic conditions. Because INNO-206 has not been previously evaluated in
      any hematologic malignancy, we determined its anti-multiple myeloma effects.
      EXPERIMENTAL DESIGN: The anti-multiple myeloma effect of INNO-206 at different pH
      levels on multiple myeloma cell proliferation using multiple myeloma cell lines
      with the MTS assay and antiangiogenic activity using the chorioallantoic
      membrane/feather bud assay were determined. The anti-multiple myeloma effects and
      toxicity of INNO-206 were also compared with conventional doxorubicin and
      PEGylated liposomal doxorubicin (PLD) alone, and in combination with bortezomib,
      using our multiple myeloma xenograft models. RESULTS: INNO-206 inhibited blood
      vessel formation and reduced multiple myeloma cell growth in a pH-dependent
      fashion. INNO-206 alone produced marked anti-multiple myeloma effects in vivo at
      doses that doxorubicin was toxic, and the combination of INNO-206 plus bortezomib
      produced increased anti-multiple myeloma effects compared with either agent
      alone. In contrast, all mice receiving bortezomib with doxorubicin or PLD died.
      CONCLUSIONS: These findings show that INNO-206 produces anti-multiple myeloma
      effects in vitro and in vivo. It also enhances the antitumor effects of
      bortezomib. These results suggest that INNO-206 may provide patients with
      multiple myeloma with an anthracycline that may be administered safely at higher
      doses compared with free doxorubicin, resulting in superior efficacy compared
      with the currently available anthracyclines to treat this B-cell malignancy.

PMID- 22619307
TI  - MARCKS regulates growth and radiation sensitivity and is a novel prognostic
      factor for glioma.
AB  - PURPOSE: This study assessed whether myristoylated alanine-rich C-kinase
      substrate (MARCKS) can regulate glioblastoma multiforme (GBM) growth, radiation
      sensitivity, and clinical outcome. EXPERIMENTAL DESIGN: MARCKS protein levels
      were analyzed in five GBM explant cell lines and eight patient-derived xenograft
      tumors by immunoblot, and these levels were correlated to proliferation rates and
      intracranial growth rates, respectively. Manipulation of MARCKS protein levels
      was assessed by lentiviral-mediated short hairpin RNA knockdown in the U251 cell
      line and MARCKS overexpression in the U87 cell line. The effect of manipulation
      of MARCKS on proliferation, radiation sensitivity, and senescence was assessed.
      MARCKS gene expression was correlated with survival outcomes in the Repository of
      Molecular Brain Neoplasia Data (REMBRANDT) Database and The Cancer Genome Atlas
      (TCGA). RESULTS: MARCKS protein expression was inversely correlated with GBM
      proliferation and intracranial xenograft growth rates. Genetic silencing of
      MARCKS promoted GBM proliferation and radiation resistance, whereas MARCKS
      overexpression greatly reduced GBM growth potential and induced senescence. We
      found MARCKS gene expression to be directly correlated with survival in both the
      REMBRANDT and TCGA databases. Specifically, patients with high MARCKS expressing
      tumors of the proneural molecular subtype had significantly increased survival
      rates. This effect was most pronounced in tumors with unmethylated O(6)
      methylguanine DNA methyltransferase (MGMT) promoters, a traditionally poor
      prognostic factor. CONCLUSIONS: MARCKS levels impact GBM growth and radiation
      sensitivity. High MARCKS expressing GBM tumors are associated with improved
      survival, particularly with unmethylated MGMT promoters. These findings suggest
      the use of MARCKS as a novel target and biomarker for prognosis in the proneural
      subtype of GBM.

PMID- 22619308
TI  - Preparation of a specific monoclonal antibody against human UDP
      glucuronosyltransferase (UGT) 1A9 and evaluation of UGT1A9 protein levels in
      human tissues.
AB  - Glucuronidation is a major detoxification pathway of drugs and xenobiotics that
      are catalyzed by the UDP-glucuronosyltransferase (UGT) superfamily. Determination
      of the protein levels of the individual UGT isoforms in human tissues is required
      for the successful extrapolation of in vitro metabolic data to in vivo clearance.
      Most previous studies evaluating UGT isoform expression were limited to the mRNA
      level because of the high degree of amino acid sequence homology between UGT
      isoforms that has hampered the availability of isoform-specific antibodies. In
      this study, we generated a peptide-specific monoclonal antibody against human
      UGT1A9. We demonstrated that this antibody does not cross-react with the other
      UGT1A isoforms including UGT1A7, UGT1A8, and UGT1A10 and shows a high degree of
      amino acid sequence similarity with UGT1A9. Using this antibody, we found that
      UGT1A9 protein is expressed in the kidney and the liver but not in the jejunum or
      the ileum, consistent with previous reports of mRNA expression. In a panel of 20
      individual human livers, the UGT1A9 protein levels exhibited 9-fold variability.
      It is noteworthy that the relative UGT1A9 protein levels were not correlated with
      the UGT1A9 mRNA level (r = -0.13), like other UGT isoforms reported previously,
      suggesting the importance of evaluating UGT isoform expression at protein levels.
      In conclusion, we generated a specific monoclonal antibody against UGT1A9 and
      evaluated the distribution and relative expression levels of the UGT1A9 protein
      in human tissues. This antibody may serve as a useful tool for further studies of
      UGT1A9 to evaluate its physiological, pharmacological, and toxicological roles in
      human tissues.

PMID- 22619309
TI  - Transcriptome analysis using a high-density oligomicroarray under drought stress
      in various genotypes of cassava: an important tropical crop.
AB  - Cassava is an important crop that provides food security and income generation in
      many tropical countries and is known for its adaptability to various
      environmental conditions. Despite its global importance, the development of
      cassava microarray tools has not been well established. Here, we describe the
      development of a 60-mer oligonucleotide Agilent microarray representing ~20,000
      cassava genes and how it can be applied to expression profiling under drought
      stress using three cassava genotypes (MTAI16, MECU72 and MPER417-003). Our
      results identified about 1300 drought stress up-regulated genes in cassava and
      indicated that cassava has similar mechanisms for drought stress response and
      tolerance as other plant species. These results demonstrate that our microarray
      is a useful tool for analysing the cassava transcriptome and that it is
      applicable for various cassava genotypes.

PMID- 22619310
TI  - A set of Lotus japonicus Gifu x Lotus burttii recombinant inbred lines
      facilitates map-based cloning and QTL mapping.
AB  - Model legumes such as Lotus japonicus have contributed significantly to the
      understanding of symbiotic nitrogen fixation. This insight is mainly a result of
      forward genetic screens followed by map-based cloning to identify causal alleles.
      The L. japonicus ecotype 'Gifu' was used as a common parent for inter-accession
      crosses to produce F2 mapping populations either with other L. japonicus
      ecotypes, MG-20 and Funakura, or with the related species L. filicaulis. These
      populations have all been used for genetic studies but segregation distortion,
      suppression of recombination, low polymorphism levels, and poor viability have
      also been observed. More recently, the diploid species L. burttii has been
      identified as a fertile crossing partner of L. japonicus. To assess its qualities
      in genetic linkage analysis and to enable quantitative trait locus (QTL) mapping
      for a wider range of traits in Lotus species, we have generated and genotyped a
      set of 163 Gifu * L. burttii recombinant inbred lines (RILs). By direct
      comparisons of RIL and F2 population data, we show that L. burttii is a valid
      alternative to MG-20 as a Gifu mapping partner. In addition, we demonstrate the
      utility of the Gifu * L. burttii RILs in QTL mapping by identifying an Nfr1
      linked QTL for Sinorhizobium fredii nodulation.

PMID- 22619311
TI  - Patient health literacy and the practice of evidence-based medicine.

PMID- 22619312
TI  - Immunostaining findings in IgA nephropathy: correlation with histology and
      clinical outcome in the Oxford Classification patient cohort.

PMID- 22619313
TI  - Risks in life after living kidney donation.

PMID- 22619314
TI  - Cumulative radiation dose from medical imaging in kidney transplant patients.
AB  - BACKGROUND: Although many patients undergoing kidney transplant are exposed to
      multiple examinations that increase cumulative effective doses (CEDs) of ionizing
      radiation, no data are available characterizing their total longitudinal
      radiation burden and relating radiation burden with risk factors for more
      exposure. METHODS: We did a retrospective cohort study of 92 patients (mean age
      52 years; range: 20-75 years) who underwent kidney transplant at University
      Hospital, Novara, Italy, that evaluated all following medical imaging procedures
      involving ionizing radiation undergone beginning June 2007, and all subsequent
      procedures through August 2011, at the centre. RESULTS: The mean and median
      annual CED were 17.2 and 4.9 millisieverts (mSv) per patient-year. The mean and
      median total CED per patient over the study period were 46.1 and 17.3 mSv,
      respectively. Twenty-eight and 12% of patients had total CED >50 and 100 mSv,
      values which are associated with a good or strong evidence of an increased cancer
      mortality risk, respectively. Computed tomography scanning accounted for 73% of
      the total CED. The annual CED was significantly higher in incident patients and
      in patients with ischaemic heart disease and cancer. CONCLUSION: In this
      institution, multiple testing of kidney transplant patients was common in many
      patients associated with high cumulative estimated doses of ionizing radiation.

PMID- 22619315
TI  - Right vertical infra-axillary mini-incision for repair of simple congenital heart
      defects: a matched-pair analysis.
AB  - OBJECTIVES: To evaluate the efficacy and safety of the right vertical infra
      axillary mini-incision (RVAI) used for the repair of simple congenital heart
      defects. METHODS: We performed a retrospective 1:1 matched-pair analysis on the
      patients with simple congenital heart defects who were operated on from February
      2003 to October 2010. All the recruited patients were treated through either RVAI
      (RVAI group) or median sternotomy incision (MSI group). In order to balance the
      major prognostic factors between the two groups, the MSI group was selected by a
      pair-matched case-control methodology and matched for heart defects, the year of
      surgery, body weight and patching. RESULTS: A total of 104 patients were
      included. The demographics and preoperative clinical characteristics of the
      patients in the RVAI group (n = 52) and in the MSI one (n = 52) were similar.
      There were no operative or late mortalities and no special care in the intensive
      care unit (ICU) or rehospitalization. The mean duration time of surgical
      operation (skin-to-skin) was 147 +/- 21 min (range from 100 to 190 min) in the
      RVAI group and 174 +/- 35 min (range from 120 to 270 min) in the MSI one (P <
      0.001), respectively. No significant difference was found between the two groups
      in the consuming time for cardiopulmonary bypass, aortic cross-clamp,
      postoperative ventilation, ICU stay, postoperative hospital stay and drainage. No
      significant residual defects were found in patients of both groups. No
      asymmetrical development of the breast, thoracic deformity or scoliosis has been
      found during the follow-up. All the patients or the parents of young children
      (100%) in the RVAI group and 34 patients or the parents of young children (65.4%)
      in the MSI one were satisfied with the cosmetic results (P < 0.001). CONCLUSIONS:
      The RVAI surgical approach to simple congenital heart defects was a safe
      procedure and could be performed with excellent cosmetic and clinical outcomes.
      It provided a good alternative to the standard MSI for simple congenital heart
      defects.

PMID- 22619316
TI  - The axillary incision to repair congenital heart defects.

PMID- 22619317
TI  - Re: The worldwide experience with the 29-mm Edwards SAPIEN XTTM transcatheter
      heart valve in patients with a large aortic annulus.

PMID- 22619318
TI  - Surgical treatment of left main disease and severe carotid stenosis: does the off
      pump technique provide a better outcome?
AB  - OBJECTIVES: Left main disease (LMD), combined with carotid artery stenosis (CAS),
      constitutes a high-risk patient population. Priority is often given to coronary
      revascularization, due to the severity of the angina. However, the choice of
      revascularization strategy [off-pump coronary artery bypass (OPCAB) vs coronary
      artery bypass grafting (CABG)] remains elusive. METHODS: A total of 1340 patients
      with LMD were non-randomly assigned to either on-pump (CABG group, n = 680) or
      off-pump (OPCAB group, n = 634) revascularization between 1 January 2006 and 21
      September 2010. Multivariable regression was used to determine the risk-adjusted
      impact of a revascularization strategy on a composite in-hospital outcome
      (MACCE), and proportional hazards regression was used to define the variables
      affecting long-term survival. RESULTS: Significant CAS was found in 130 patients:
      84 (13.1%) patients underwent OPCAB, while 46 patients (6.8%) underwent CABG (P <
      0.05). Patients with a history of stroke/transient ischaemic attack were also
      more likely to receive OPCAB (7.1 vs 4.7%; P = 0.08). OPCAB patients were older,
      in a higher New York Heart Association (NYHA) class, with a lower LVEF and higher
      EuroSCORE. A calcified aorta was found in 79 patients [OPCAB-CABG: 49 (7.73%) vs
      30 (4.41%); P = 0.016] and resulted in a less complex revascularization (OPCAB
      CABG: 2.3 +/- 0.71 vs 3.19 +/- 0.82; P < 0.05), and 30-day mortality was
      insignificantly higher in the CABG (2.7 vs 2.8%) as well as MACCE (11.2 vs 12.2%;
      P = NS). This trend reversed when late mortality was evaluated; however, it did
      not reach significance at 60 months. Preoperative renal impairment requiring
      dialysis was found to be a technique-independent predictor of MACCE. The number
      of arterial conduits also influenced MACCE. CONCLUSIONS: Off-pump coronary
      revascularization may offer risk reduction of neurological complications in
      patients with a significant carotid artery disease and a history of previous
      stroke, but a larger study population is needed to support this thesis. The
      growing discrepancy in long-term survival should draw attention to a more
      complete revascularization in OPCAB patients.

PMID- 22619319
TI  - Plasmodium falciparum erythrocyte membrane protein 1 domain cassettes 8 and 13
      are associated with severe malaria in children.
AB  - The clinical outcome of Plasmodium falciparum infections ranges from asymptomatic
      parasitemia to severe malaria syndromes associated with high mortality. The
      virulence of P. falciparum infections is associated with the type of P.
      falciparum erythrocyte membrane protein 1 (PfEMP1) expressed on the surface of
      infected erythrocytes to anchor these to the vascular lining. Although var2csa,
      the var gene encoding the PfEMP1 associated with placental malaria, was
      discovered in 2003, the identification of the var/PfEMP1 variants associated with
      severe malaria in children has remained elusive. To identify var/PfEMP1 variants
      associated with severe disease outcome, we compared var transcript levels in
      parasites from 88 children with severe malaria and 40 children admitted to the
      hospital with uncomplicated malaria. Transcript analysis was performed by RT
      quantitative PCR using a set of 42 primer pairs amplifying var subtype-specific
      loci covering most var/PfEMP1 subtypes. In addition, we characterized the near
      full-length sequence of the most prominently expressed var genes in three
      patients diagnosed with severe anemia and/or cerebral malaria. The combined
      analysis showed that severe malaria syndromes, including severe anemia and
      cerebral malaria, are associated with high transcript levels of PfEMP1 domain
      cassette 8-encoding var genes. Transcript levels of group A var genes, including
      genes encoding domain cassette 13, were also significantly higher in patients
      with severe syndromes compared with those with uncomplicated malaria. This study
      specifies the var/PfEMP1 types expressed in severe malaria in children, and
      thereby provides unique targets for future efforts to prevent and treat severe
      malaria infections.

PMID- 22619320
TI  - Spontaneous transmitter release is critical for the induction of long-term and
      intermediate-term facilitation in Aplysia.
AB  - Long-term plasticity can differ from short-term in recruiting the growth of new
      synaptic connections, a process that requires the participation of both the
      presynaptic and postsynaptic components of the synapse. How does information
      about synaptic plasticity spread from its site of origin to recruit the other
      component? The answer to this question is not known in most systems. We have
      investigated the possible role of spontaneous transmitter release as such a
      transsynaptic signal. Until recently, relatively little has been known about the
      functions of spontaneous release. In this paper, we report that spontaneous
      release is critical for the induction of a learning-related form of synaptic
      plasticity, long-term facilitation in Aplysia. In addition, we have found that
      this signaling is engaged quite early, during an intermediate-term stage that is
      the first stage to involve postsynaptic as well as presynaptic molecular
      mechanisms. In a companion paper, we show that spontaneous release from the
      presynaptic neuron acts as an orthograde signal to recruit the postsynaptic
      mechanisms of intermediate-term facilitation and initiates a cascade that can
      culminate in synaptic growth with additional stimulation during long-term
      facilitation. Spontaneous release could make a similar contribution to learning
      related synaptic plasticity in mammals.

PMID- 22619321
TI  - A restricted subset of var genes mediates adherence of Plasmodium falciparum
      infected erythrocytes to brain endothelial cells.
AB  - Cerebral malaria (CM) is a deadly complication of Plasmodium falciparum
      infection, but specific interactions involved in cerebral homing of infected
      erythrocytes (IEs) are poorly understood. In this study, P. falciparum-IEs were
      characterized for binding to primary human brain microvascular endothelial cells
      (HBMECs). Before selection, CD36 or ICAM-1-binding parasites exhibited punctate
      binding to a subpopulation of HBMECs and binding was CD36 dependent. Panning of
      IEs on HBMECs led to a more dispersed binding phenotype and the selection of
      three var genes, including two that encode the tandem domain cassette 8 (DC8) and
      were non-CD36 binders. Multiple domains in the DC8 cassette bound to brain
      endothelium and the cysteine-rich interdomain region 1 inhibited binding of P.
      falciparum-IEs by 50%, highlighting a key role for the DC8 cassette in cerebral
      binding. It is mysterious how deadly binding variants are maintained in the
      parasite population. Clonal parasite lines expressing the two brain-adherent DC8
      var genes did not bind to any of the known microvascular receptors, indicating
      unique receptors are involved in cerebral binding. They could also adhere to
      brain, lung, dermis, and heart endothelial cells, suggesting cerebral binding
      variants may have alternative sequestration sites. Furthermore, young African
      children with CM or nonsevere control cases had antibodies to HBMEC-selected
      parasites, indicating they had been exposed to related variants during childhood
      infections. This analysis shows that specific P. falciparum erythrocyte membrane
      protein 1 types are linked to cerebral binding and suggests a potential mechanism
      by which individuals may build up immunity to severe disease, in the absence of
      CM.

PMID- 22619323
TI  - Profile of Shinya Yamanaka.

PMID- 22619324
TI  - Computational model of a circulation current that controls electrochemical
      properties in the mammalian cochlea.
AB  - Sound-evoked mechanical stimuli permit endolymphatic K(+) to enter sensory hair
      cells. This transduction is sensitized by an endocochlear potential (EP) of +80
      mV in endolymph. After depolarizing the cells, K(+) leaves hair cells in
      perilymph, and it is then circulated back to endolymph across the lateral
      cochlear wall. In theory, this process entails a continuous and unidirectional
      current carried by apical K(+) channels and basolateral K(+) uptake transporters
      in both the marginal cell and syncytial layers of the lateral wall. The
      transporters regulate intracellular and extracellular [K(+)], allowing the
      channels to form K(+) diffusion potentials across each of the two layers. These
      diffusion potentials govern the EP. What remains uncertain is whether these
      transport mechanisms accumulating across diverse cell layers make up a continuous
      circulation current in the lateral wall and how this current might affect the
      characteristics of the endolymph. To address this question, we developed an
      electrophysiological model that incorporates channels and transporters of the
      lateral wall and channels of hair cells that derive a circulation current. The
      simulation replicated normal experimental EP values and reproduced experimentally
      measured changes in the EP and intra- and extracellular [K(+)] in the lateral
      wall when different transporters and channels were blocked. The model predicts
      that, under these different conditions, the circulation current's contribution to
      the EP arises from different sources. Finally, our model also accurately
      simulated EP loss in a mouse model of a chloride channelopathy associated with
      deafness.

PMID- 22619325
TI  - Knockout of the prion protein (PrP)-like Sprn gene does not produce embryonic
      lethality in combination with PrP(C)-deficiency.
AB  - The Sprn gene encodes Shadoo (Sho), a glycoprotein with biochemical properties
      similar to the unstructured region of cellular prion protein (PrP(C)). Sho has
      been considered a candidate for the hypothetical pi protein that supplies a
      PrP(C)-like function to maintain the viability of Prnp(0/0) mice lacking the
      PrP(C) protein. To understand these relationships more clearly we probed the cell
      biology of Sho and created knockout mice. Besides full-length and a "C1" C
      terminal fragment, we describe a 6-kDa N-terminal Sho neuropeptide, "N1," which
      is present in membrane-enriched subcellular fractions of wild-type mice. Sprn
      null alleles were produced that delete all protein coding sequences yet spare the
      Mtg1 gene transcription unit that overlaps the Sprn 3' UTR; the resulting mice
      bred to homozygosity were viable and fertile, although Sprn(0/0) mice maintained
      in two genetic backgrounds weighed less than wild-type mice. Lack of Sho protein
      did not affect prion incubation time. Contrasting with lethality reported for
      knockdown of expression in Prnp(0/0) embryos using lentiviruses targeted against
      the Sprn 3' UTR, we established that double-knockout mice deficient in both Sho
      and PrP(C) are fertile and viable up to 690 d of age. Our data reduce the impetus
      for equating Sho with the notional pi protein and are not readily reconciled with
      hypotheses wherein expression of PrP(C) and Sho are both required for completion
      of embryogenesis. Alternatively, and in accord with some reports for PrP(C), we
      infer that Sho's activity will prove germane to the maintenance of neuronal
      viability in postnatal life.

PMID- 22619326
TI  - Apolipoprotein A-IV improves glucose homeostasis by enhancing insulin secretion.
AB  - Apolipoprotein A-IV (apoA-IV) is secreted by the small intestine in response to
      fat absorption. Here we demonstrate a potential role for apoA-IV in regulating
      glucose homeostasis. ApoA-IV-treated isolated pancreatic islets had enhanced
      insulin secretion under conditions of high glucose but not of low glucose,
      suggesting a direct effect of apoA-IV to enhance glucose-stimulated insulin
      release. This enhancement involves cAMP at a level distal to Ca(2+) influx into
      the beta cells. Knockout of apoA-IV results in compromised insulin secretion and
      impaired glucose tolerance compared with WT mice. Challenging apoA-IV(-/-) mice
      with a high-fat diet led to fasting hyperglycemia and more severe glucose
      intolerance associated with defective insulin secretion than occurred in WT mice.
      Administration of exogenous apoA-IV to apoA-IV(-/-) mice improved glucose
      tolerance by enhancing insulin secretion in mice fed either chow or a high-fat
      diet. Finally, we demonstrate that exogenous apoA-IV injection decreases blood
      glucose levels and stimulates a transient increase in insulin secretion in KKAy
      diabetic mice. These results suggest that apoA-IV may provide a therapeutic
      target for the regulation of glucose-stimulated insulin secretion and treatment
      of diabetes.

PMID- 22619327
TI  - Heme-protein vibrational couplings in cytochrome c provide a dynamic link that
      connects the heme-iron and the protein surface.
AB  - The active site of cytochrome c (Cyt c) consists of a heme covalently linked to a
      pentapeptide segment (Cys-X-X-Cys-His), which provides a link between the heme
      and the protein surface, where the redox partners of Cyt c bind. To elucidate the
      vibrational properties of heme c, nuclear resonance vibrational spectroscopy
      (NRVS) measurements were performed on (57)Fe-labeled ferric Hydrogenobacter
      thermophilus cytochrome c(552), including (13)C(8)-heme-, (13)C(5)(15)N-Met-, and
      (13)C(15)N-polypeptide (pp)-labeled samples, revealing heme-based vibrational
      modes in the 200- to 450-cm(-1) spectral region. Simulations of the NRVS spectra
      of H. thermophilus cytochrome c(552) allowed for a complete assignment of the Fe
      vibrational spectrum of the protein-bound heme, as well as the quantitative
      determination of the amount of mixing between local heme vibrations and pp modes
      from the Cys-X-X-Cys-His motif. These results provide the basis to propose that
      heme-pp vibrational dynamic couplings play a role in electron transfer (ET) by
      coupling vibrations of the heme directly to vibrations of the pp at the protein
      protein interface. This could allow for the direct transduction of the thermal
      (vibrational) energy from the protein surface to the heme that is released on
      protein/protein complex formation, or it could modulate the heme vibrations in
      the protein/protein complex to minimize reorganization energy. Both mechanisms
      lower energy barriers for ET. Notably, the conformation of the distal Met side
      chain is fine-tuned in the protein to localize heme-pp mixed vibrations within
      the 250- to 400-cm(-1) spectral region. These findings point to a particular
      orientation of the distal Met that maximizes ET.

PMID- 22619328
TI  - Molecular actions of smoking cessation drugs at alpha4beta2 nicotinic receptors
      defined in crystal structures of a homologous binding protein.
AB  - Partial agonists of the alpha4beta2 nicotinic acetylcholine receptor (nAChR),
      such as varenicline, are therapeutically used in smoking cessation treatment.
      These drugs derive their therapeutic effect from fundamental molecular actions,
      which are to desensitize alpha4beta2 nAChRs and induce channel opening with
      higher affinity, but lower efficacy than a full agonist at equal receptor
      occupancy. Here, we report X-ray crystal structures of a unique acetylcholine
      binding protein (AChBP) from the annelid Capitella teleta, Ct-AChBP, in complex
      with varenicline or lobeline, which are both partial agonists. These structures
      highlight the architecture for molecular recognition of these ligands, indicating
      the contact residues that potentially mediate their molecular actions in
      alpha4beta2 nAChRs. We then used structure-guided mutagenesis and
      electrophysiological recordings to pinpoint crucial interactions of varenicline
      with residues on the complementary face of the binding site in alpha4beta2
      nAChRs. We observe that residues in loops D and E are molecular determinants of
      desensitization and channel opening with limited efficacy by the partial agonist
      varenicline. Together, this study analyzes molecular recognition of smoking
      cessation drugs by nAChRs in a structural context.

PMID- 22619329
TI  - Molecular basis of Tank-binding kinase 1 activation by transautophosphorylation.
AB  - Tank-binding kinase (TBK)1 plays a central role in innate immunity: it serves as
      an integrator of multiple signals induced by receptor-mediated pathogen detection
      and as a modulator of IFN levels. Efforts to better understand the biology of
      this key immunological factor have intensified recently as growing evidence
      implicates aberrant TBK1 activity in a variety of autoimmune diseases and
      cancers. Nevertheless, key molecular details of TBK1 regulation and substrate
      selection remain unanswered. Here, structures of phosphorylated and
      unphosphorylated human TBK1 kinase and ubiquitin-like domains, combined with
      biochemical studies, indicate a molecular mechanism of activation via
      transautophosphorylation. These TBK1 structures are consistent with the
      tripartite architecture observed recently for the related kinase IKKbeta, but
      domain contributions toward target recognition appear to differ for the two
      enzymes. In particular, both TBK1 autoactivation and substrate specificity are
      likely driven by signal-dependent colocalization events.

PMID- 22619330
TI  - A subset of group A-like var genes encodes the malaria parasite ligands for
      binding to human brain endothelial cells.
AB  - Cerebral malaria is the most deadly manifestation of infection with Plasmodium
      falciparum. The pathology of cerebral malaria is characterized by the
      accumulation of infected erythrocytes (IEs) in the microvasculature of the brain
      caused by parasite adhesins on the surface of IEs binding to human receptors on
      microvascular endothelial cells. The parasite and host molecules involved in this
      interaction are unknown. We selected three P. falciparum strains (HB3, 3D7, and
      IT/FCR3) for binding to a human brain endothelial cell line (HBEC-5i). The whole
      transcriptome of isogenic pairs of selected and unselected parasites was analyzed
      using a variant surface antigen-supplemented microarray chip. After selection,
      the most highly and consistently up-regulated genes were a subset of group A-like
      var genes (HB3var3, 3D7_PFD0020c, ITvar7, and ITvar19) that showed 11- to >100
      fold increased transcription levels. These var genes encode P. falciparum
      erythrocyte membrane protein (PfEMP)1 variants with distinct N-terminal domain
      types (domain cassette 8 or domain cassette 13). Antibodies to HB3var3 and
      PFD0020c recognized the surface of live IEs and blocked binding to HBEC-5i,
      thereby confirming the adhesive function of these variants. The clinical in vivo
      relevance of the HBEC-selected parasites was supported by significantly higher
      surface recognition of HBEC-selected parasites compared with unselected parasites
      by antibodies from young African children suffering cerebral malaria (Mann
      Whitney test, P = 0.029) but not by antibodies from controls with uncomplicated
      malaria (Mann-Whitney test, P = 0.58). This work describes a binding phenotype
      for virulence-associated group A P. falciparum erythrocyte membrane protein 1
      variants and identifies targets for interventions to treat or prevent cerebral
      malaria.

PMID- 22619332
TI  - Spike timing plays a key role in synapse elimination at the neuromuscular
      junction.
AB  - Nerve impulse activity produces both developmental and adult plastic changes in
      neural networks. For development, however, its precise role and the mechanisms
      involved remain elusive. Using the classic model of synapse competition and
      elimination at newly formed neuromuscular junctions, we asked whether spike
      timing is the instructive signal at inputs competing for synaptic space. Using a
      rat strain whose soleus muscle is innervated by two nerves, we chronically evoked
      different temporal spike patterns in the two nerves during synapse formation in
      the adult. We found that asynchronous activity imposed upon the two nerves
      promotes synapse elimination, provided that their relative spikes are separated
      by 25 ms or more; remarkably, this elimination occurs even though an equal number
      of spikes were evoked in the competing axons. On the other hand, when spikes are
      separated by 20 ms or less, activity is perceived as synchronous, and elimination
      is prevented. Thus, in development, as in adult plasticity, precise spike timing
      plays an instructive role in synaptic modification.

PMID- 22619331
TI  - Positional cloning and characterization reveal the molecular basis for soybean
      maturity locus E1 that regulates photoperiodic flowering.
AB  - The complex and coordinated regulation of flowering has high ecological and
      agricultural significance. The maturity locus E1 has a large impact on flowering
      time in soybean, but the molecular basis for the E1 locus is largely unknown.
      Through positional cloning, we delimited the E1 locus to a 17.4-kb region
      containing an intron-free gene (E1). The E1 protein contains a putative bipartite
      nuclear localization signal and a region distantly related to B3 domain. In the
      recessive allele, a nonsynonymous substitution occurred in the putative nuclear
      localization signal, leading to the loss of localization specificity of the E1
      protein and earlier flowering. The early-flowering phenotype was consistently
      observed in three ethylmethanesulfonate-induced mutants and two natural mutations
      that harbored a premature stop codon or a deletion of the entire E1 gene. E1
      expression was significantly suppressed under short-day conditions and showed a
      bimodal diurnal pattern under long-day conditions, suggesting its response to
      photoperiod and its dominant effect induced by long day length. When a functional
      E1 gene was transformed into the early-flowering cultivar Kariyutaka with low E1
      expression, transgenic plants carrying exogenous E1 displayed late flowering.
      Furthermore, the transcript abundance of E1 was negatively correlated with that
      of GmFT2a and GmFT5a, homologues of FLOWERING LOCUS T that promote flowering.
      These findings demonstrated the key role of E1 in repressing flowering and
      delaying maturity in soybean. The molecular identification of the maturity locus
      E1 will contribute to our understanding of the molecular mechanisms by which a
      short-day plant regulates flowering time and maturity.

PMID- 22619334
TI  - Diagnostic criteria for gestational diabetes: who decides?

PMID- 22619333
TI  - Spontaneous transmitter release recruits postsynaptic mechanisms of long-term and
      intermediate-term facilitation in Aplysia.
AB  - Whereas short-term (minutes) facilitation at Aplysia sensory-motor neuron
      synapses is presynaptic, long-term (days) facilitation involves synaptic growth,
      which requires both presynaptic and postsynaptic mechanisms. How are the
      postsynaptic mechanisms recruited, and when does that process begin? We have been
      investigating the possible role of spontaneous transmitter release from the
      presynaptic neuron. In the previous paper, we found that spontaneous release is
      critical for the induction of long-term facilitation, and this process begins
      during an intermediate-term stage of facilitation that is the first stage to
      involve postsynaptic as well as presynaptic mechanisms. We now report that
      increased spontaneous release during the short-term stage acts as an orthograde
      signal to recruit postsynaptic mechanisms of intermediate-term facilitation
      including increased IP3, Ca(2+), and membrane insertion and recruitment of
      clusters of AMPA-like receptors, which may be first steps in synaptic growth
      during long-term facilitation. These results suggest that the different stages of
      facilitation involve a cascade of pre- and postsynaptic mechanisms, which is
      initiated by spontaneous release and may culminate in synaptic growth.

PMID- 22619335
TI  - Vanishing lung syndrome.

PMID- 22619337
TI  - MCAT revisions finalized.

PMID- 22619338
TI  - Should hiding HIV status always be a crime?

PMID- 22619339
TI  - Indifferent reporting of notifiable diseases.

PMID- 22619340
TI  - Refugee health reforms assailed.

PMID- 22619341
TI  - Effect of maternal weight, adipokines, glucose intolerance and lipids on infant
      birth weight among women without gestational diabetes mellitus.
AB  - BACKGROUND: The delivery of excess maternal nutrients to the fetus is known to
      increase the risk of macrosomia, even among infants of women without gestational
      diabetes mellitus. With the current obesity epidemic, maternal adiposity and its
      associated effects on circulating adipokines and inflammatory proteins may now
      have a greater impact on fetal growth. We sought to evaluate the independent
      effects of maternal glycemia, lipids, obesity, adipokines and inflammation on
      infant birth weight. METHODS: We included 472 women who underwent an oral glucose
      tolerance test in late pregnancy and were found not to have gestational diabetes;
      104 (22.0%) had gestational impaired glucose tolerance. We also measured fasting
      levels of insulin, low-and high-density lipoprotein cholesterol, triglycerides,
      leptin, adiponectin and C-reactive protein. Obstetric outcomes were assessed at
      delivery. RESULTS: The mean birth weight was 3481 g (standard deviation 493 g);
      68 of the infants were large for gestational age. On multiple linear regression
      analysis, positive determinants of birth weight were length of gestation, male
      infant, weight gain during pregnancy up to the time of the oral glucose tolerance
      test, body mass index (BMI) before pregnancy and impaired glucose tolerance in
      pregnancy. Leptin, adiponectin and C-reactive protein levels were each negatively
      associated with birth weight. On logistic regression analysis, the significant
      metabolic predictors of having a large-for-gestational-age infant were BMI before
      pregnancy (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.05-1.27, per 1
      kg/m(2) increase), weight gain during pregnancy up to the time of the oral
      glucose tolerance test (OR 1.12, 95% CI 1.05-1.19, per 1 kg increase) and leptin
      level (OR 0.50, 95% CI 0.30-0.82, per 1 standard deviation change).
      INTERPRETATION: Among women without gestational diabetes, maternal adiposity and
      leptin levels were the strongest metabolic determinants of having a large-for
      gestational-age infant rather than glucose intolerance and lipid levels.

PMID- 22619342
TI  - The perilous state of independent randomized clinical trials and related applied
      research in Canada.

PMID- 22619344
TI  - Rich? Inquisitive? Confused? Book a safari to the "wild side" of private boutique
      medicine.

PMID- 22619345
TI  - Anaphylaxis from bee pollen supplement.

PMID- 22619346
TI  - Saskatchewan medical school mulls overhaul.

PMID- 22619347
TI  - Expression profile of apoptosis-related genes in childhood adrenocortical tumors:
      low level of expression of BCL2 and TNF genes suggests a poor prognosis.
AB  - BACKGROUND: Impaired apoptosis has been implicated in the development of
      childhood adrenocortical tumors (ACT), although the expression of apoptosis
      related gene expression in such tumors has not been reported. METHODS: The mRNA
      expression levels of the genes CASP3, CASP8, CASP9, FAS, TNF, NFKB, and BCL2 were
      analyzed by quantitative real-time PCR in consecutive tumor samples obtained at
      diagnosis from 60 children with a diagnosis of ACT and in 11 non-neoplastic
      adrenal samples. BCL2 and TNF protein expression was analyzed by
      immunohistochemistry. RESULTS: A significant association was observed between
      tumor size >=100 g and lower expression levels of the BCL2 (P=0.03) and TNF
      (P=0.05) genes; between stage IV and lower expression levels of CASP3 (P=0.008),
      CASP9 (P=0.02), BCL2 (P=0.002), TNF (P=0.05), and NFKB (P=0.03); Weiss score >=3
      and lower expression of TNF (P=0.01); unfavorable event and higher expression
      values of CASP9 (P=0.01) and lower values of TNF (P=0.02); and death and lower
      expression of BCL2 (P=0.04). Underexpression of TNF was associated with lower
      event-free survival in uni- and multivariate analyses (P<0.01). Similar results
      were observed when patients with Weiss score <3 were excluded. CONCLUSION: This
      study supports the participation of apoptosis-related genes in the biology and
      prognosis of childhood ACT and suggests the complex role of these genes in the
      pathogenesis of this tumor.

PMID- 22619348
TI  - A novel severe N-terminal splice site KISS1R gene mutation causes
      hypogonadotropic hypogonadism but enables a normal development of neonatal
      external genitalia.
AB  - BACKGROUND: Kisspeptin 1 receptor (KISS1R) gene mutations are rare but have
      recently become an important etiology of normosmic isolated hypogonadotropic
      hypogonadism (IHH). OBJECTIVES: To characterize the genetic defect, the
      phenotype, and response to therapy of three IHH siblings with a novel severe
      KISS1R mutation. PATIENTS AND METHODS: Three siblings (16- and 22-year-old
      sisters and their 20-year-old brother) born to consanguineous parents with normal
      neonatal external genitalia presented with no pubertal development, normosmia,
      and a low response to GNRH stimulation. Homozygosity mapping, KISS1R gene
      sequencing, and RNA expression were performed. RESULTS: The females' basal low
      estradiol level (50 pmol/l) failed to rise in response to human chorionic
      gonadotropin (hCG). The brother's low testosterone (1.87 nmol/l) responded to
      combined hCG and human menopausal gonadotropin (hCG) and HMG therapies, but the
      testes remained small (1-2 ml). Secondary sexual characteristics were attained by
      exogenous sex steroid replacement. SNP array studies revealed shared homozygosity
      for a chromosome 19 region encompassing KISS1R. Sequencing revealed a novel
      homozygous KISS1R mutation at the nt-1 canonical acceptor splice site of intron 1
      in affected siblings. The mother (menarche at 14 years) was heterozygous. cDNA
      sequencing showed that the G>A mutation results in skipping of exon 2 and a
      premature stop codon at residue 151. CONCLUSIONS: The novel severe N-terminal
      KISS1R splice site (c.245-1G>A) mutation results in IHH. Heterozygous female
      carriers may manifest a subtle fertile phenotype. The subnormal gonadal response
      to hCG in patients may implicate a direct role of KISS1R in gonadal function. The
      normal neonatal virilization in a male homozygous to this severe mutation
      challenges the hypothesis that KISS1R is required for fetal development of male
      external genitalia.

PMID- 22619350
TI  - Malignant and benign thyroid nodules after total body irradiation preceding
      hematopoietic cell transplantation during childhood.
AB  - BACKGROUND: The risk of radiation-induced benign and malignant thyroid nodules is
      well known. OBJECTIVE: The aim of this study was to determine the occurrence of
      thyroid nodules and carcinomas after fractionated total body irradiation (TBI)
      preceding hematopoietic stem cell transplantation (HSCT) for malignant
      hematological disease during childhood. METHODS: We conducted a retrospective
      university hospital-based observational study. The participants were 76 patients
      receiving fractionated TBI between 1989 and 2009 as part of the conditioning
      regimen for HSCT to treat malignant hematological disease, with a median age of
      8.2 (5.7-11.4) years, for whom the last ultrasound examination was performed at a
      median age of 14.2 (11.2-17) years. The main outcome measure was cumulative
      incidence of thyroid nodules detected by ultrasound scans followed by biopsy if
      necessary. RESULTS: Thyroid nodules were examined in 21 (28%) patients, six (29%)
      of whom were diagnosed with thyroid carcinoma at the age of 2.2-18.6 years after
      TBI. The cumulative incidence of nodule occurrence increased with increasing time
      from diagnosis. The 10-year cumulative incidence of benign and malignant thyroid
      nodules was 16% (95% confidence interval (CI) 4-27%) and 8% (95% CI 0-16%)
      respectively. Seventeen (22%) patients had hypothyroidism (compensated n=12, in
      five patients it was transient). No significant independent risk factors were
      identified in the multivariable competing risk model as a function of nodule
      occurrence. CONCLUSION: Short-term and life-long monitoring, with screening for
      nodules of the thyroid gland using ultrasound scans, is recommended for survivors
      subjected to TBI for HSCT during childhood.

PMID- 22619349
TI  - Low-dose dexamethasone administration for 3 weeks favorably affects plasma HDL
      concentration and composition but does not affect very low-density lipoprotein
      kinetics.
AB  - OBJECTIVE: Subclinical hypercortisolemia often occurs in subjects with features
      of the metabolic syndrome, and it has been suggested that it may be, at least in
      part, responsible for the development of these metabolic abnormalities. However,
      the metabolic effects of glucocorticoid administration to mimic subclinical
      glucocorticoid excess have not been evaluated. METHODS: We used stable isotope
      labeled tracer methods in conjunction with magnetic resonance techniques to
      measure the effect of glucocorticoid excess within the physiological range (~0.7
      mg dexamethasone/day for 3 weeks) on glucose and free fatty acid (FFA) rates of
      appearance (Ra) into plasma, intrahepatic triglyceride (TG) content, very low
      density lipoprotein (VLDL)-TG and VLDL-apolipoprotein B-100 (apoB-100) kinetics
      and plasma lipoprotein subclass concentrations, and particle sizes in nine
      overweight and obese individuals. RESULTS: Dexamethasone treatment led to a very
      small but significant increase in body weight (from 87.4+/-7.1 to 88.6+/-7.2 kg;
      P=0.003) and increased HDL-cholesterol (from 45.9+/-2.8 to 55.1+/-4.6 mg/dl;
      P=0.037) and HDL particle (from 33.7+/-2.2 to 41.4+/-4.2 nmol/l; P=0.023)
      concentrations in plasma but had no effect on intrahepatic TG content, glucose
      and FFA Ra in plasma, hepatic VLDL-TG and VLDL-apoB-100 secretion rates and mean
      residence times in the circulation, plasma TG and LDL-cholesterol concentrations,
      and plasma lipoprotein particle sizes. CONCLUSION: Subclinical hypercortisolemia
      does not have significant adverse metabolic consequences.

PMID- 22619351
TI  - The relationship between anatomically correct electric and magnetic field
      dosimetry and publishe delectric and magnetic field exposure limits.
AB  - Electric and magnetic field exposure limits published by International Commission
      for Non-Ionizing Radiation Protection and Institute of Electrical and Electronics
      Engineers are aimed at protection against adverse electrostimulation, which may
      occur by direct coupling to excitable tissue and, in the case of electric fields,
      through indirect means associated with surface charge effects (e.g. hair
      vibration, skin sensations), spark discharge and contact current. For direct
      coupling, the basic restriction (BR) specifies the not-to-be-exceeded induced
      electric field. The key results of anatomically based electric and magnetic field
      dosimetry studies and the relevant characteristics of excitable tissue were first
      identified. This permitted us to assess the electric and magnetic field exposure
      levels that induce dose in tissue equal to the basic restrictions, and the
      relationships of those exposure levels to the limits now in effect. We identify
      scenarios in which direct coupling of electric fields to peripheral nerve could
      be a determining factor for electric field limits.

PMID- 22619352
TI  - A study of environmental radioactivity measurements in the Samsun province,
      Turkey.
AB  - This study was concerned with the measurement of natural and artificial
      radionuclides in soil samples and indoor radon concentrations in the Samsun
      province, Turkey. In soil samples, the values of individual mean activity of
      (226)Ra, (232)Th, (40)K and (137)Cs radionuclides were found to be 31, 22, 341
      and 16 Bq kg(-1), respectively. The radiological parameters, such as the absorbed
      dose rate in air, the annual effective dose (AED) and excess lifetime cancer
      risk, were calculated. Indoor radon measurements were carried out with CR-39
      based radon dosemeters at 127 dwellings in the Samsun province. The mean annual
      (222)Rn activity was found to be 106 Bq m(-3) (equivalent to an AED of 1.88 mSv).
      The seasonal variation of (222)Rn activity shows that maximum levels are observed
      in the winter, while minimum levels are observed in the summer. The mean lifetime
      fatality risk for the studied area was estimated at 1.45*10(-4). The results
      obtained did not significantly differ from those obtained in other parts of the
      country.

PMID- 22619353
TI  - Commentary on Education and training: radiation protection courses for diagnostic
      radiology in Turkey.

PMID- 22619354
TI  - Reporting of post-polyethylene glycol prolactin: precipitation by polyethylene
      glycol 6000 or polyethylene glycol 8000 will change reference intervals for
      monomeric prolactin.
AB  - BACKGROUND: When screening for macroprolactin, many laboratories use
      precipitation by polyethylene glycol (PEG) with molecular weight 6000 (PEG6000)
      or 8000 (PEG8000), and report the percentage prolactin recovery. It has been
      proposed that reporting of percentage prolactin recovery should be replaced by
      absolute post-PEG prolactin; however, the post-PEG prolactin reference interval
      has been established using PEG6000 only. We sought to determine whether the use
      of PEG8000, instead of PEG6000, changed post-PEG prolactin concentrations.
      METHODS: We compared the post-PEG6000 and post-PEG8000 prolactin concentrations
      in hyperprolactinaemic serum samples referred for macroprolactin screening
      (n=40), using Passing-Bablok regression analysis and Bland-Altman difference
      plot. RESULTS: The median (25th-75th percentile, range) total prolactin, post
      PEG6000 and post-PEG8000 prolactin concentrations were, respectively, 36 (31-46,
      23-83) MUg/L, 27 (20-38, 18-72) MUg/L and 24 (18-35, 16-64) MUg/L for male serum
      samples (n=5); and 56 (39-83, 24-596) MUg/L, 45 (31-67, 8-503) MUg/L and 41 (28
      62, 6-457) MUg/L for female serum samples (n=35) (mIU/L conversion factor: 21.2).
      The Passing-Bablok analysis demonstrated a significant constant bias of -1.27 and
      a non-significant proportional bias of 0.96. The Bland-Altman plot showed a bias
      of -8.2% (95% limits of agreement -19.3-2.9%). CONCLUSIONS: There is a
      significant constant bias between the two macroprolactin precipitation methods.
      We changed our PEG precipitation to a PEG6000 method. Laboratories that use
      PEG8000 should consider the transference of the reference interval established
      with PEG6000 carefully.

PMID- 22619355
TI  - Multimodality imaging of an inadvertently placed defibrillator lead in the left
      ventricle.

PMID- 22619356
TI  - Atypical cardiac magnetic resonance findings in a case of suspected
      endomyocardial fibrosis.

PMID- 22619357
TI  - Diffusion-weighted magnetic resonance imaging of the normal endometrium: temporal
      and spatial variations of the apparent diffusion coefficient.
AB  - BACKGROUND: Diffusion-weighted magnetic resonance imaging (DWI) is increasingly
      used in the diagnosis of endometrial disease. No complete knowledge, however,
      exists yet of the influence of physiology on the endometrial apparent diffusion
      coefficient (ADC) values on which DWI is based. PURPOSE: To establish whether the
      ADC values measured with DWI in the endometrium of healthy reproductive-aged
      women significantly vary from the early proliferative to the periovulatory phase
      of the menstrual cycle and between the fundus and the isthmus of the uterus.
      MATERIAL AND METHODS: In 17 women the endometrial ADC values measured on the
      fifth menstrual day, both at the fundus and at the isthmus of the uterus, were
      compared to the values obtained on the 14th day before the subsequent cycle. In
      81 women (menstrual day: fifth through 21st) the endometrial ADC values measured
      at the fundus were compared to the values obtained at the isthmus of the uterus.
      All examinations were performed with a 1.5 T magnet (b values: 0 and 800
      mm/s(2)). The results were analyzed by means of Student's t-test per paired data.
      RESULTS: The endometrial ADC values measured on the fifth day of the menstrual
      cycle were lower than those obtained in the periovulatory phase both at the
      fundus (mean 0.923 vs. 1.256 * 10(-3) mm(2)/s) and at the isthmus (mean 1.297 vs.
      1.529 * 10(-3) mm(2)/s) of the uterus. The endometrial ADC values measured at the
      fundus of the uterus were lower than those obtained at the isthmus (mean 1.132
      vs. 1.420 * 10(-3) mm(2)/s) through the menstrual cycle. All these differences
      were highly significant (P < 0.001) at statistical analysis. CONCLUSION:
      Physiological variations occurring in endometrial ADC values of healthy women
      should be considered by the radiologists when interpreting DWI examinations in
      patients with endometrial disease.

PMID- 22619358
TI  - Knockdown of the adipokinetic hormone receptor increases feeding frequency in the
      two-spotted cricket Gryllus bimaculatus.
AB  - Adipokinetic hormone (AKH) is a peptide hormone that regulates the nutritional
      state in insects by supporting the mobilization of lipids. In the present study,
      we manipulated AKH signaling to evaluate how metabolic state regulates feeding in
      an orthopteran insect, the two-spotted cricket, Gryllus bimaculatus. This was
      accomplished by RNA interference (RNAi) targeting the receptor gene for AKH [G.
      bimaculatus AKHR (GrybiAKHR)]. We found that the knockdown of GrybiAKHR by AKHR
      double-stranded RNA treatment decreased the levels of 1,2-diacylglycerol and
      trehalose in the hemolymph, whereas it increased the level of triacylglycerol in
      the fat body. In addition, the knockdown of GrybiAKHR enhanced starvation
      resistance and increased food intake. Furthermore, direct observation of
      GrybiAKHR(RNAi) crickets revealed that the knockdown of GrybiAKHR increased
      feeding frequency but did not alter meal duration, whereas locomotor activity
      decreased. The increased frequency of feeding by GrybiAKHR(RNAi) crickets
      eventually resulted in an increase of food intake. These data demonstrate that
      the regulation of the metabolic state by AKH signaling affects feeding frequency,
      probably through nutritional control.

PMID- 22619359
TI  - Raf-1, a potential therapeutic target, mediates early steps in endometriosis
      lesion development by endometrial epithelial and stromal cells.
AB  - Endometriosis is a hormone-sensitive gynecological disorder characterized by the
      benign growth of endometrial-like tissue in the pelvic cavity. Endometriotic
      lesions composed of endometrial stromal cells (ESC) and glandular epithelial
      cells (EEC) are thought to arise from menstrual endometrial tissue reaching the
      pelvic cavity via retrograde menstruation. The cause of endometriotic lesion
      formation is still not clear. Recent evidence suggest that cytokines may play a
      role in the early development of endometriosis lesions. Because cytokines and
      growth factors signal via the v-raf-1 murine leukemia viral oncogene homolog 1
      (Raf-1) kinase pathway, we have examined the role of Raf-1 in early steps of
      endometriosis lesion formation, specifically attachment of endometrial cells to
      peritoneal mesothelial cells (PMC) and invasion of endometrial cells through PMC
      (trans-mesothelial invasion). Raf-1 antagonist GW5074 decreased attachment to PMC
      and trans-mesothelial invasion by primary EEC and ESC. Raf-1 also mediated
      TGFbeta-induced trans-mesothelial invasion by the established, low-invasive EEC
      line EM42. TGFbeta treatment of EEC resulted in Raf-1 phosphorylation at S338 and
      phosphorylation of ERK, suggesting that TGFbeta activates Raf-1 signaling in
      these cells. GW5074 had little effect on ESC proliferation but inhibited EEC
      growth significantly under reduced serum conditions. Antagonizing Raf-1 activity
      and expression via GW5074 and specific Raf-1 small interfering RNA, respectively,
      did not alter EEC resistance to growth inhibition by TGFbeta. Raf-1 inhibition
      blocked induction of EEC growth by epidermal growth factor. Our data suggest that
      Raf-1 may mediate pathologic steps involved in early endometriosis lesion
      formation and may be a mediator of TGFbeta and epidermal growth factor actions in
      endometriosis.

PMID- 22619360
TI  - Endoplasmic reticulum stress induces the expression of fetuin-A to develop
      insulin resistance.
AB  - Fetuin-A is a biomarker reported to be important in many metabolic disorders,
      including obesity, diabetes, and hepatic steatosis. Although it is well known
      that fetuin-A is increased in diabetes and nonalcoholic fatty liver disease
      (NAFLD), the levels of fetuin-A in diabetic patients with NAFLD are unknown.
      Furthermore, the regulation of fetuin-A expression is still obscure. In this
      study, a total of 180 age- and sex-matched subjects with normal glucose
      tolerance, NAFLD, newly diagnosed diabetes (NDD), and NDD with NAFLD were
      recruited. We found that the levels of fetuin-A were significantly increased in
      NDD with NAFLD as compared with NDD or NAFLD subjects. We further used HepG2
      cells to investigate the regulation of fetuin-A. Treatment with endoplasmic
      reticulum (ER) stress activator, thapsigargin, increased the expression of fetuin
      A mRNA and protein in a time- and dose-dependent manner. Pretreatment with ER
      stress inhibitor, 4-phenylbutyrate, reversed high glucose or palmitate-induced
      fetuin-A expression. Moreover, treatment with 4-phenylbutyrate in both
      streptozotocin-induced and high-fat diet-induced diabetic mice not only decreased
      hepatic fetuin-A levels but also improved hyperglycemia. Taken together, we found
      that fetuin-A levels were increased in diabetes patients with NAFLD. Moreover, ER
      stress induced by high glucose and palmitate increased the expression of fetuin-A
      and further contributed to the development of insulin resistance.

PMID- 22619361
TI  - Hepatic Src homology phosphatase 2 regulates energy balance in mice.
AB  - The Src homology 2 domain-containing protein-tyrosine phosphatase Src homology
      phosphatase 2 (Shp2) is a negative regulator of hepatic insulin action in mice
      fed regular chow. To investigate the role of hepatic Shp2 in lipid metabolism and
      energy balance, we determined the metabolic effects of its deletion in mice
      challenged with a high-fat diet (HFD). We analyzed body mass, lipid metabolism,
      insulin sensitivity, and glucose tolerance in liver-specific Shp2-deficient mice
      (referred to herein as LSHKO) and control mice fed HFD. Hepatic Shp2 protein
      expression is regulated by nutritional status, increasing in mice fed HFD and
      decreasing during fasting. LSHKO mice gained less weight and exhibited increased
      energy expenditure compared with control mice. In addition, hepatic Shp2
      deficiency led to decreased liver steatosis, enhanced insulin-induced suppression
      of hepatic glucose production, and impeded the development of insulin resistance
      after high-fat feeding. At the molecular level, LSHKO exhibited decreased hepatic
      endoplasmic reticulum stress and inflammation compared with control mice. In
      addition, tyrosine and serine phosphorylation of total and mitochondrial signal
      transducer and activator of transcription 3 were enhanced in LSHKO compared with
      control mice. In line with this observation and the increased energy expenditure
      of LSHKO, oxygen consumption rate was higher in liver mitochondria of LSHKO
      compared with controls. Collectively, these studies identify hepatic Shp2 as a
      novel regulator of systemic energy balance under conditions of high-fat feeding.

PMID- 22619362
TI  - Frequent gain and loss of intronic splicing regulatory elements during the
      evolution of vertebrates.
AB  - Splicing regulatory elements (SREs) are sequences bound by proteins that
      influence splicing of nearby splice sites. Constitutively spliced introns have
      evolved to utilize many different splicing factors. The evolutionary processes
      that influenced which splicing factors are used for splicing of individual
      introns are generally unclear. We demonstrate that in the lineage that gave rise
      to mammals, many introns lost U-rich sequences and gained G-rich sequences, both
      of which resemble known SREs. The apparent conversion of U-rich to G-rich SREs
      suggests that the associated splicing factors are functionally equivalent. In
      support of this we demonstrated that U-rich and G-rich SREs are both capable of
      promoting splicing of an SRE-dependent splicing reporter. Furthermore, we
      demonstrate, using the heterologous MS2 tethering system (bacterial MS2 coat
      fusion-protein and its RNA stem-loop binding site), that both the U-rich SRE
      binding protein (TIA1) and the G-rich SRE-binding protein (HNRNPF) can promote
      splicing of the same intron. We also observed that gain of G-rich SREs is
      significantly associated with G/C-rich genomic isochores, suggesting that gain or
      loss of SREs was driven by the same processes that ultimately resulted in the
      formation of mammalian genomic isochores. We propose the following model for the
      gain and loss of mammalian SREs. Ancestral U-rich SREs located in genomic regions
      that were experiencing high rates of A/T to G/C conversion would have suffered
      frequent deleterious mutations. However, this same process resulted in increased
      formation of functionally equivalent G-rich SREs, and acquisition of new G-rich
      SREs decreased purifying selection on the U-rich SREs, which were then free to
      decay.

PMID- 22619363
TI  - Physical tethering and volume exclusion determine higher-order genome
      organization in budding yeast.
AB  - In this paper we show that tethering of heterochromatic regions to nuclear
      landmarks and random encounters of chromosomes in the confined nuclear volume are
      sufficient to explain the higher-order organization of the budding yeast genome.
      We have quantitatively characterized the contact patterns and nuclear territories
      that emerge when chromosomes are allowed to behave as constrained but otherwise
      randomly configured flexible polymer chains in the nucleus. Remarkably, this
      constrained random encounter model explains in a statistical manner the
      experimental hallmarks of the S. cerevisiae genome organization, including (1)
      the folding patterns of individual chromosomes; (2) the highly enriched
      interactions between specific chromatin regions and chromosomes; (3) the
      emergence, shape, and position of gene territories; (4) the mean distances
      between pairs of telomeres; and (5) even the co-location of functionally related
      gene loci, including early replication start sites and tRNA genes. Therefore,
      most aspects of the yeast genome organization can be explained without calling on
      biochemically mediated chromatin interactions. Such interactions may modulate the
      pre-existing propensity for co-localization but seem not to be the cause for the
      observed higher-order organization. The fact that geometrical constraints alone
      yield a highly organized genome structure, on which different functional elements
      are specifically distributed, has strong implications for the folding principles
      of the genome and the evolution of its function.

PMID- 22619364
TI  - Endoscopic assessment of the oesophageal features of eosinophilic oesophagitis:
      validation of a novel classification and grading system.
AB  - OBJECTIVE: Abnormalities are commonly identified during endoscopy in eosinophilic
      oesophagitis (EoE). There is no standardised classification to describe these
      features. This study aimed to evaluate the interobserver agreement of a grading
      system for the oesophageal features of EoE. METHOD: The proposed system
      incorporated the grading of four major oesophageal features (rings, furrows,
      exudates, oedema) and the presence of additional features of narrow calibre
      oesophagus, feline oesophagus, stricture and crepe paper oesophagus. Endoscopic
      videos from 25 patients with EoE and controls were reviewed by 21
      gastroenterologists. Interobserver agreement was assessed by estimating multi
      rater kappa and the proportion of pairwise agreement. RESULTS: Using the original
      grading system, agreement for rings, furrows and exudates was moderate
      (kappa=0.38-0.46, 56-65% agreement) but poor for oedema (kappa=0.23, 51%
      agreement). Identification of narrow calibre oesophagus had fair agreement
      (kappa=0.30, 74% agreement) while feline oesophagus had poor agreement
      (kappa=0.15, 68% agreement). After collapsing the severity grading for oedema and
      furrows and eliminating poorly performing features of feline oesophagus and
      narrow calibre oesophagus, a modified grading system demonstrated good agreement
      for the four major features of EoE (kappa=0.40-0.54, 71-81% agreement) and
      additional features of stricture and crepe paper oesophagus (kappa=0.52 and 0.58,
      79% and 92% agreement). CONCLUSIONS: The proposed system for endoscopically
      identified oesophageal features of EoE defines common nomenclature and severity
      scores for the assessment of EoE disease activity. The system has good
      interobserver agreement among practising and academic gastroenterologists.

PMID- 22619365
TI  - An unusual cause of obscure gastrointestinal bleeding in a patient with
      cirrhosis.

PMID- 22619366
TI  - Kinetics of the histological, serological and symptomatic responses to gluten
      challenge in adults with coeliac disease.
AB  - OBJECTIVE: Coeliac disease is defined by gluten responsiveness, yet there are few
      data on gluten challenge (GC) in adults on a gluten-free diet. Lack of data
      regarding the kinetics of responses to gluten is a limitation in clinical
      practice and research when GC is performed. DESIGN: 20 adults with biopsy-proven
      coeliac disease participated. The study included two run-in visits followed by a
      14-day GC at a randomly assigned dose of 3 or 7.5 g of gluten/day. Study visits
      occurred 3, 7, 14 and 28 days after starting GC. Duodenal biopsy was performed
      during the run-in and at days 3 and 14 of GC. Villous height to crypt depth ratio
      (Vh:Cd) and intraepithelial lymphocyte (IEL) count/100 enterocytes were measured
      by two pathologists. Antibodies to tissue transglutaminase and deamidated gliadin
      peptides, lactulose to mannitol ratio (LAMA) and symptoms were assessed at each
      visit. RESULTS: Significant reduction in Vh:Cd (2.2-1.1, p<0.001) and increase in
      IELs (32.6-51.8, p<0.001) were seen from baseline to day 14. Antibody titres
      increased slightly from baseline to day 14 of GC but markedly by day 28. LAMA did
      not change significantly. Gastrointestinal symptoms increased significantly by
      day 3 and returned to baseline by day 28. No differences were seen between the
      two gluten doses. CONCLUSIONS: 14 day GC at >= 3 g of gluten/day induces
      histological and serological changes in the majority of adults with coeliac
      disease. These data permit accurate design of clinical trials and indicate that
      many individuals will meet coeliac diagnostic criteria after a 2-week GC.

PMID- 22619367
TI  - Preoperative biological therapy and short-term outcomes of abdominal surgery in
      patients with inflammatory bowel disease.
AB  - OBJECTIVE: Previous investigations of short-term outcomes after preoperative
      exposure to biological therapy in inflammatory bowel disease (IBD) were
      conflicting. The authors aimed to assess postoperative outcomes in patients who
      underwent abdominal surgery with recent exposure to anti-tumour necrosis factor
      therapy. DESIGN: A retrospective case-control study with detailed matching was
      performed for subjects with IBD with and without exposure to biologics within 180
      days of abdominal surgery. Postoperative outcomes were compared between the
      groups. RESULTS: 473 procedures were reviewed consisting of 195 patients with
      exposure to biologics and 278 matched controls. There were no significant
      differences in most postoperative outcomes such as: length of stay, fever (>=
      38.5 degrees C), urinary tract infection, pneumonia, bacteraemia, readmission,
      reoperations and mortality. On univariate analysis, procedures on biologics had
      more wound infections compared with controls (19% vs 11%; p=0.008), but this was
      not significant in multivariate analysis. Concomitant therapy with biologics and
      thiopurines was associated with increased frequencies of urinary tract infections
      (p=0.0007) and wound infections (p=0.0045). Operations performed <= 14 days from
      last biologic dose had similar rates of infections and other outcomes when
      compared with those performed within 15-30 days or 31-180 days. Patients with
      detectable preoperative infliximab levels had similar rates of wound infection
      compared with those with undetectable levels (3/10 vs 0/9; p=0.21). CONCLUSION:
      Preoperative treatment with TNF-alpha antagonists in patients with IBD is not
      associated with most early postoperative complications. A shorter time interval
      from last biological dose is not associated with increased postoperative
      complications. In most cases, surgery should not be delayed, and appropriate
      biological therapy may be continued perioperatively.

PMID- 22619369
TI  - A proteomic study of protein variation between osteopenic and age-matched control
      bone tissue.
AB  - The focus of this study was to identify changes in protein expression within the
      bone tissue environment between osteopenic and control bone tissue of human
      femoral neck patients with osteoarthritis. Femoral necks were compared from
      osteopenic patients and age-matched controls. A new method of bone protein
      extraction was developed to provide a swift, clear view of the bone proteome.
      Relative changes in protein expression between control and osteopenic samples
      were quantified using difference gel electrophoresis (DIGE) technology after
      affinity chromatographic depletion of albumin and IgG. The proteins that were
      determined to be differentially expressed were identified using standard liquid
      chromatography mass spectrometry (LC/MS/MS) and database searching techniques. In
      order to rule out blood contamination, blood from age-matched osteoporotic,
      osteopenic and controls were analyzed in a similar manner. Image analysis of the
      DIGE gels indicated that 145 spots in the osteopenic bone samples changed at
      least +/- 1.5-fold from the control samples (P < 0.05). Three of the proteins
      were identified by LC/MS/MS. Of the proteins that increased in the osteopenic
      femurs, two were especially significant: carbonic anhydrase I and
      phosphoglycerate kinase 1. Apolipoprotein A-I was the most prominent protein that
      significantly decreased in the osteopenic femurs. The blood samples revealed no
      significant differences between groups for any of these proteins. In conclusion,
      carbonic anhydrase I, phosphoglycerate kinase 1 and apolipoprotein A-I appeared
      to be the most significant variations of proteins in patients with osteopenia and
      osteoarthritis.

PMID- 22619368
TI  - Oral contraceptives, reproductive factors and risk of inflammatory bowel disease.
AB  - BACKGROUND: Oral contraceptive use has been associated with risk of Crohn's
      disease (CD) and ulcerative colitis (UC). OBJECTIVE: To determine whether this
      association is confounded or modified by other important lifestyle and
      reproductive factors. DESIGN: A prospective cohort study was carried out of
      117,375 US women enrolled since 1976 in the Nurses Health Study I (NHS I) and
      115,077 women enrolled since 1989 in the Nurses' Health Study II (NHS II) with no
      prior history of UC or CD. These women had provided information every 2 years, on
      age at menarche, oral contraceptive use, parity, menopause status and other risk
      factors. Diagnoses of CD and UC were confirmed by review of medical records. Cox
      proportional hazards models were used to calculate HRs and 95% CIs. RESULTS:
      Among 232,452 women with over 5,030,196 person-years of follow-up, 315 cases of
      CD and 392 cases of UC were recorded through 2007 in NHS II and 2008 in NHS I.
      Compared with never users of oral contraceptives, the multivariate-adjusted HRs
      for CD were 2.82 (95% CI 1.65 to 4.82) among current users and 1.39 (95% CI 1.05
      to 1.85) among past users. The association between oral contraceptives and UC
      differed according to smoking history (pheterogeneity=0.04). Age at menarche, age
      at first birth and parity were not associated with risk of UC or CD. CONCLUSION:
      In two large prospective cohorts of US women, oral contraceptive use was
      associated with risk of CD. The association between oral contraceptive use and UC
      was limited to women with a history of smoking.

PMID- 22619370
TI  - Correlations between ultrasonographic characteristics of corpora lutea and
      systemic concentrations of progesterone during the discrete stages of corpora
      lutea lifespan and secretory activity in cyclic ewes.
AB  - Associations between physical characteristics and functionality of corpora lutea
      (CL) have previously been reported in monovulatory species, albeit several
      studies in cattle and humans have refuted the existence of temporal relationships
      between CL size, echotexture and serum progesterone (P(4)) concentrations. The
      main objective of the present study was to examine whether or not there were
      correlations between ultrasonographic image attributes of CL and systemic
      concentrations of P(4) during the discrete stages of the luteal phase in two
      breeds of sheep differing in ovulation rates (non-prolific Western White Face
      [WWF] ewes and prolific Finn [F] sheep). Transrectal ovarian ultrasonography
      utilized a 7.5-MHz linear-array transducer connected to a portable scanner (Aloka
      SSD-500) and the images were analyzed using commercially available image
      analytical software (Image ProPlus((r))) validated for the present application in
      sheep. The correlations were assessed using the Pearson's Product Moment (PPM)
      analysis and also, to increase the accuracy of statistical tests, the analysis of
      covariance (ANCOVA), with the number of CL as a co-factor. In WWF ewes, serum
      concentrations of P(4) correlated significantly with the total luteal area (TLA)
      during the CL growth phase (days 3-6; day 0 = ovulation) and functional
      luteolysis (days 12-15), and with numerical pixel values (NPVs--pixel intensity)
      during luteolysis; the results obtained by using two different statistical
      methods were generally similar. In prolific F ewes, serum P(4) concentrations
      were directly correlated with TLA during CL growth (days 3-6; ANCOVA), functional
      luteolysis (days 13-14; PPM), and structural CL regression (days 11-14; PPM and
      ANCOVA), and with NPVs during functional luteolysis (PPM and ANCOVA). We
      concluded that systemic P(4) concentrations could only be accurately predicted
      from the changes in luteal area during CL growth and regression, and from NPVs
      during luteolysis, in both prolific and non-prolific ewes, but the changes in
      size and echotexture of the luteal glands at mid-cycle were not indicative of
      serum P(4) concentrations in sheep.

PMID- 22619371
TI  - Y-box binding protein-1 implicated in translational control of fetal myocardial
      gene expression after cardiac transplant.
AB  - Peri-transplant surgical trauma and ischemia/reperfusion injury in accepted
      murine heterotopic heart grafts has been associated with myofibroblast
      differentiation, cardiac fibrosis and biomechanical-stress activation of the
      fetal myocardial smooth muscle alpha-actin (SMalphaA) gene. The wound-healing
      agonists, transforming growth factor beta1 and thrombin, are known to coordinate
      SMalphaA mRNA transcription and translation in activated myofibroblasts by
      altering the subcellular localization and mRNA-binding affinity of the Y-box
      binding protein-1 (YB-1) cold-shock domain (CSD) protein that governs a variety
      of cellular responses to metabolic stress. YB-1 accumulated in polyribosome
      enriched regions of the sarcoplasm proximal to cardiac intercalated discs in
      accepted heart grafts. YB-1 binding to a purine-rich motif in exon 3 of SMalphaA
      mRNA that regulates translational efficiency increased substantially in perfusion
      isolated, rod-shaped adult rat cardiomyocytes during phenotypic de
      differentiation in the presence of serum-derived growth factors. Cardiomyocyte de
      differentiation was accompanied by the loss of a 60 kDa YB-1 variant that was
      highly expressed in both adult myocardium and freshly isolated myocytes and
      replacement with the 50 kDa form of YB-1 (p50) typically expressed in
      myofibroblasts that demonstrated sequence-specific interaction with SMalphaA
      mRNA. Accumulation of p50 YB-1 in reprogrammed, de-differentiated myocytes was
      associated with a 10-fold increase in SMalphaA protein expression. Endomyocardial
      biopsies collected from patients up to 14 years after heart transplant showed
      variable yet coordinately elevated expression of SMalphaA and p50 YB-1 protein
      and demonstrable p50 YB-1:SMalphaA mRNA interaction. The p60 YB-1 variant in
      human heart graft samples, but neither mouse p60 nor mouse or human p50, reacted
      with an antibody specific for the phosphoserine 102 modification in the YB-1 CSD.
      Modulation of YB-1 subcellular compartmentalization and mRNA-binding activity may
      be linked with reprogramming of contractile protein gene expression in
      ventricular cardiomyocytes that could contribute to maladaptive remodeling in
      accepted, long-term heart grafts.

PMID- 22619372
TI  - Contribution of the paraventricular nucleus in autonomic adjustments to heat
      stress.
AB  - We assessed the contribution of the paraventricular nucleus (PVN) in the heat
      stress-mediated changes in sympathetic nerve activity and blood flow
      redistribution from the core to the skin surface. Renal sympathetic nerve
      activity (RSNA), mean arterial pressure (MAP), heart rate (HR), and body and tail
      temperatures were recorded in anesthetized rats after bilateral microinjection of
      cerebrospinal fluid (CSF), lidocaine or NG-monomethyl-L-arginine (L-NMMA) into
      the PVN during heat stress. Heat stress was induced by a graded increase in the
      temperature of a heating pad for 30 min. Heat stimulus after blockade of the PVN
      with lidocaine resulted in a blunted RSNA response (DeltaRSNA: 117.6 +/- 17.0%
      versus 11.3 +/- 7.3%), as well as blunted MAP and HR (DeltaMAP: 22 +/- 2 versus 
      0.04 +/- 7.2 mmHg; DeltaHR: 93.4 +/- 9.3 versus 43.4 +/- 18.8 bpm). Body
      temperature threshold for tail vasodilation was unaffected by lidocaine
      treatment. The increase in RSNA, MAP and HR due to heat stress in L-NMMA-treated
      rats reached similar levels as CSF-treated control rats. However, a higher body
      temperature threshold for tail vasodilation was observed after L-NMMA injection
      (37.3 +/- 0.1 versus 37.8 +/- 0.2  degrees C). In conclusion, an intact PVN
      contributes to an increase in renal sympathetic activity provoked by heat stress,
      resulting in cardiovascular adjustments that influence core blood redistribution
      to the periphery. Furthermore, during heat stress, the effect of the PVN on
      cutaneous vasodilation is dependent on a nitric oxide mechanism.

PMID- 22619373
TI  - Streptozotocin-nicotinamide-induced diabetes in the rat. Characteristics of the
      experimental model.
AB  - Administration of both streptozotocin (STZ) and nicotinamide (NA) has been
      proposed to induce experimental diabetes in the rat. STZ is well known to cause
      pancreatic B-cell damage, whereas NA is administered to rats to partially protect
      insulin-secreting cells against STZ. STZ is transported into B-cells via the
      glucose transporter GLUT2 and causes DNA damage leading to increased activity of
      poly(ADP-ribose) polymerase (PARP-1) to repair DNA. However, exaggerated activity
      of this enzyme results in depletion of intracellular NAD(+) and ATP, and the
      insulin-secreting cells undergo necrosis. The protective action of NA is due to
      the inhibition of PARP-1 activity. NA inhibits this enzyme, preventing depletion
      of NAD(+) and ATP in cells exposed to STZ. Moreover, NA serves as a precursor of
      NAD(+) and thereby additionally increases intracellular NAD(+) levels. The
      severity of diabetes in experimental rats strongly depends on the doses of STZ
      and NA given to these animals. Therefore, in diabetic rats, blood glucose may be
      changed in a broad range--from slight hyperglycemia to substantial hyperglycemia
      compared with control animals. Similarly, blood insulin may be only slightly
      decreased or substantial hypoinsulinemia may be induced. In vitro studies
      demonstrated that the insulin-secretory response to glucose is attenuated in STZ
      NA-induced diabetic rats compared with control animals. This is due to reduced B
      cell mass as well as metabolic defects in the insulin-secreting cells. Results of
      numerous experiments have demonstrated that this model of diabetes is useful in
      studies of different aspects of diabetes.

PMID- 22619374
TI  - Approaches to economic evaluation in telemedicine.
AB  - External validity or generalizability is a major challenge in the economic
      evaluation of telemedicine. There are two possible ways of increasing
      generalizability: the first is to use a pragmatic trial design so it better
      reflects normal patient caseload and everyday practice. The second is to use
      existing data from the literature and decision modelling to estimate the expected
      costs and outcomes of different alternatives. The first will increase
      generalizability to other patients than those in the trial and the second will
      increase generalizability from place to place. The objective and role of the
      evaluation will decide the most appropriate evaluation approach. Pragmatic trials
      should be used in studies where the objective is to provide measurements of costs
      and outcomes for a specific group of patients in a particular setting. This
      approach is highly relevant in telemedicine evaluations where the objective is to
      support local investments strategies and reimbursement systems. Decision
      modelling provides an overall structure for a decision problem and a formal
      analysis of the implications of different decisions. Modelling can simulate a
      trial or mimic a current system or a system that decision makers would like to
      use. Modelling is a useful approach when decisions need to be made about whether
      to invest in telemedicine within a broader context.

PMID- 22619375
TI  - National telemental health responses to a major bushfire disaster.
AB  - In response to the Victorian bushfire disaster in 2009, various telemental health
      services were provided by three national agencies: Kids Helpline (BoysTown),
      MensLine Australia (Crisis Support Services) and Lifeline Australia. All provider
      agencies used their existing national service structures and staff resources,
      which were expanded to respond to bushfire-related service demand. We examined
      service provider reports and conducted key informant interviews. Despite a lack
      of quantitative data on consumer outcomes and perspectives, it appears that all
      three telemental health services experienced significant increases in overall
      service uptake levels in the wake of the bushfires. Uptake of specialized
      telephone-, web-, email- and crisis counselling services was substantial,
      although that of callback services was very limited. Potential clients
      encountered specific barriers in relation to service access and the callback
      model. The bushfire experience highlighted the impact of transitory living
      circumstances and the increased complexity of post-disaster calls on service
      provision. Telemental health services need to be integrated into mainstream
      services and disaster response structures.

PMID- 22619376
TI  - Brain weight-body weight ratio in sudden infant death syndrome revisited.
AB  - AIMS: To determine whether the brain-body weight ratio is increased in sudden
      infant death syndrome (SIDS). METHODS: Review of autopsy files from Forensic
      Science SA, South Australia was undertaken over an eight-year period from 1999 to
      2006, with classification of cases according to the San Diego definition. Sudden
      and/or unexpected deaths in previously healthy infants due to asphyxia or
      infection were selected as controls. RESULTS: There were 42 SIDS cases and 25
      controls. The SIDS cases were aged from 1 to 42 weeks (mean: 16.26 +/- 1.5 weeks)
      with a male to female ratio of 26:16. The control infants were aged from 3 to 48
      weeks (mean: 19.24 +/- 2.9 weeks) (P > 0.05) (M:F = 16:9) and included 13 cases
      of asphyxia and 12 cases of sepsis. Comparison of the brain-body weight ratios
      failed to demonstrate a significant difference: SIDS mean = 0.121 +/- 0.003;
      control mean = 0.115 +/- 0.003 (P > 0.05). CONCLUSION: Although, there was a
      trend towards higher brain-body weight ratios in SIDS infants, this did not reach
      significance. The role of brain weight in the aetiology of SIDS remains
      controversial.

PMID- 22619377
TI  - Spg20-/- mice reveal multimodal functions for Troyer syndrome protein spartin in
      lipid droplet maintenance, cytokinesis and BMP signaling.
AB  - Hereditary spastic paraplegias (HSPs; SPG1-48) are inherited neurological
      disorders characterized by lower extremity spasticity and weakness. Loss-of
      function mutations in the SPG20 gene encoding spartin cause autosomal recessive
      Troyer syndrome (SPG20), which has additional features of short stature,
      cognitive deficits and distal amyotrophy. To identify cellular impairments
      underlying Troyer syndrome, we generated Spg20-/- mice, which exhibit progressive
      gait defects. Although gross central nervous system pathology appeared largely
      normal, cerebral cortical neurons cultured from neonatal Spg20-/- mice exhibited
      increased axon branching, a phenotype suppressed by reintroducing spartin and
      which required its interaction with the endosomal sorting complex required for
      transport (ESCRT)-III protein IST1. Analysis of the bone morphogenetic protein
      (BMP) signaling pathway in Spg20-/- embryonic fibroblasts indicated that Smad1/5
      phosphorylation is modestly elevated, possibly due to alterations in BMP receptor
      trafficking. Cytokinesis was impaired in embryonic fibroblasts cultured from
      Spg20-/- mice, and binucleated chondrocytes were prominent in epiphyseal growth
      plates of bones in Spg20-/- mice, perhaps explaining the short stature of
      patients. Finally, adipose tissue from Spg20-/- female mice exhibited increased
      lipid droplet (LD) numbers and alterations in perilipin levels, supporting a role
      for spartin in LD maintenance. Taken together, our results support multimodal
      functions for spartin that provide important insights into HSP pathogenesis.

PMID- 22619378
TI  - Deep intronic mutation in OFD1, identified by targeted genomic next-generation
      sequencing, causes a severe form of X-linked retinitis pigmentosa (RP23).
AB  - X-linked retinitis pigmentosa (XLRP) is genetically heterogeneous with two
      causative genes identified, RPGR and RP2. We previously mapped a locus for a
      severe form of XLRP, RP23, to a 10.71 Mb interval on Xp22.31-22.13 containing 62
      genes. Candidate gene screening failed to identify a causative mutation, so we
      adopted targeted genomic next-generation sequencing of the disease interval to
      determine the molecular cause of RP23. No coding variants or variants within or
      near splice sites were identified. In contrast, a variant deep within intron 9 of
      OFD1 increased the splice site prediction score 4 bp upstream of the variant.
      Mutations in OFD1 cause the syndromic ciliopathies orofaciodigital syndrome-1,
      which is male lethal, Simpson-Golabi-Behmel syndrome type 2 and Joubert syndrome.
      We tested the effect of the IVS9+706A>G variant on OFD1 splicing in vivo. In RP23
      patient-derived RNA, we detected an OFD1 transcript with the insertion of a
      cryptic exon spliced between exons 9 and 10 causing a frameshift, p.N313fs.X330.
      Correctly spliced OFD1 was also detected in patient-derived RNA, although at
      reduced levels (39%), hence the mutation is not male lethal. Our data suggest
      that photoreceptors are uniquely susceptible to reduced expression of OFD1 and
      that an alternative disease mechanism can cause XLRP. This disease mechanism of
      reduced expression for a syndromic ciliopathy gene causing isolated retinal
      degeneration is reminiscent of CEP290 intronic mutations that cause Leber
      congenital amaurosis, and we speculate that reduced dosage of correctly spliced
      ciliopathy genes may be a common disease mechanism in retinal degenerations.

PMID- 22619380
TI  - Epigenetic markers of prostate cancer in plasma circulating DNA.
AB  - Epigenetic differences are a common feature of many diseases, including cancer,
      and disease-associated changes have even been detected in bodily fluids. DNA
      modification studies in circulating DNA (cirDNA) may lead to the development of
      specific non-invasive biomarkers. To test this hypothesis, we investigated cirDNA
      modifications in prostate cancer patients with locally confined disease (n = 19),
      in patients with benign prostate hyperplasias (n = 20) and in men without any
      known prostate disease (n = 20). This initial discovery screen identified 39
      disease-associated changes in cirDNA modification, and seven of these were
      validated using the sodium bisulfite-based mapping of modified cytosines in both
      the discovery cohort and an independent 38-patient validation cohort. In
      particular, we showed that the DNA modification of regions adjacent to the gene
      encoding ring finger protein 219 distinguished prostate cancer from benign
      hyperplasias with good sensitivity (61%) and specificity (71%). We also showed
      that repetitive sequences detected in this study were meaningful, as they
      indicated a highly statistically significant loss of DNA at the pericentromeric
      region of chromosome 10 in prostate cancer patients (p = 1.8 * 10(-6)). Based on
      these strong univariate results, we applied machine-learning techniques to
      develop a multi-locus biomarker that correctly distinguished prostate cancer
      samples from unaffected controls with 72% accuracy. Lastly, we used systems
      biology techniques to integrate our data with publicly available DNA modification
      and transcriptomic data from primary prostate tumors, thereby prioritizing genes
      for further studies. These data suggest that cirDNA epigenomics are promising
      source for non-invasive biomarkers.

PMID- 22619379
TI  - Microarray expression analysis and identification of serum biomarkers for Niemann
      Pick disease, type C1.
AB  - Niemann-Pick disease type C (NPC) is a lysosomal storage disorder characterized
      by liver disease and progressive neurodegeneration. Deficiency of either NPC1 or
      NPC2 leads to the accumulation of cholesterol and glycosphingolipids in late
      endosomes and early lysosomes. In order to identify pathological mechanisms
      underlying NPC and uncover potential biomarkers, we characterized liver gene
      expression changes in an Npc1 mouse model at six ages spanning the pathological
      progression of the disease. We identified altered gene expression at all ages,
      including changes in asymptomatic, 1-week-old mice. Biological pathways showing
      early altered gene expression included: lipid metabolism, cytochrome P450 enzymes
      involved in arachidonic acid and drug metabolism, inflammation and immune
      responses, mitogen-activated protein kinase and G-protein signaling, cell cycle
      regulation, cell adhesion and cytoskeleton remodeling. In contrast, apoptosis and
      oxidative stress appeared to be late pathological processes. To identify
      potential biomarkers that could facilitate monitoring of disease progression, we
      focused on a subset of 103 differentially expressed genes that encode secreted
      proteins. Further analysis identified two secreted proteins with increased serum
      levels in NPC1 patients: galectin-3 (LGALS3), a pro-inflammatory molecule, and
      cathepsin D (CTSD), a lysosomal aspartic protease. Elevated serum levels of both
      proteins correlated with neurological disease severity and appeared to be
      specific for NPC1. Expression of Lgals3 and Ctsd was normalized following
      treatment with 2-hydroxypropyl-beta-cyclodextrin, a therapy that reduces
      pathological findings and significantly increases Npc1(-/-) survival. Both LGALS3
      and CTSD have the potential to aid in diagnosis and serve as biomarkers to
      monitor efficacy in therapeutic trials.

PMID- 22619381
TI  - Infection of endovascular abdominal aortic aneurysm stent graft after urosepsis:
      case report and review of the literature.
AB  - Infection of endovascular abdominal aneurysm stent grafts is an uncommon but
      known complication. Inoculation with bacteria of the endovascular abdominal
      aneurysm stent graft during the actual implantation, in the periprocedural
      hospitalization or later due to an aortoenteric fistula, has been described in
      the literature. We report a case of endovascular abdominal aortic aneurysm stent
      graft infection occurring 40 months after implantation in a patient doing well up
      to an episode of urosepsis. In conclusion, we postulate that poor intraluminal
      healing of stent grafts, as observed in several explant studies, may result in a
      higher susceptibility to episodes of bacteremia than prosthetic vascular grafts
      inserted during open repair. We therefore consider the administration of
      prophylactic antibiotics in patients with endovascular stent grafts during
      periods with a likelihood of bacteremia.

PMID- 22619382
TI  - What, after all, is the truth: response to McGorry.

PMID- 22619383
TI  - A case of valproate-induced encephalopathy.

PMID- 22619384
TI  - A place to live: housing needs for people with psychotic disorders identified in
      the second Australian National Survey of Psychosis.
AB  - OBJECTIVE: Access to adequate housing consistent with personal preferences and
      needs is a human right and supports recovery from psychosis. This study aimed to:
      (1) describe people with psychosis living in different housing types, and their
      preferences and needs; (2) explore selected demographic and social inclusion
      correlates in relation to housing; and (3) compare two subgroups - participants
      living in supported group accommodation and supported housing - on key
      demographic, functional, clinical and social inclusion variables. METHOD: Current
      housing, preferences, needs and assistance, and housing-related social inclusion
      variables were assessed in a two-phase prevalence survey conducted within seven
      catchment areas across five Australian states. Two supported housing models were
      compared: supported group accommodation and supported housing (rental
      accommodation with in-reach support). Descriptive statistics were used. RESULTS:
      Of the total participants (n = 1825), one half were living in public or private
      rented housing (48.6%) and 22.7% were waiting for public housing. Despite being
      the preferred form of housing, only 13.1% were living in their own home. One in
      20 participants (5.2%) was currently homeless; 12.8% had been homeless in the
      previous 12 months. Residents of supported group accommodation felt safer in
      their locality than those in supported housing, but experienced less privacy and
      choice. CONCLUSIONS: Although fewer participants were homeless compared with the
      first Australian survey of psychosis, the proportion remains high. Housing
      difficulties are experienced by people with psychoses living in various
      accommodation and concern housing adequacy and safety as well as autonomy and
      choice. Access to public housing is restricted compared with the identified need.
      Since residents of supported group accommodation felt safer in their locality
      than those in supported housing, but experienced less privacy and choice, each
      supported housing model may offer different advantages to people with psychosis,
      and contribute to services that support and maintain recovery.

PMID- 22619385
TI  - X chromosome inactivation in the cycle of life.
AB  - Female mammalian cells silence one of their two X chromosomes, resulting in equal
      expression levels of X-encoded genes in female XX and male XY cells. In mice, the
      X chromosomes in female cells go through sequential steps of inactivation and
      reactivation. Depending on the developmental time window, imprinted or random X
      chromosome inactivation (XCI) is initiated, and both processes lead to an
      inactive X chromosome that is clonally inherited. Here, we review new insights
      into the life cycle of XCI and provide an overview of the mechanisms regulating X
      inactivation and reactivation.

PMID- 22619386
TI  - Evolutionary crossroads in developmental biology: cyclostomes (lamprey and
      hagfish).
AB  - Lampreys and hagfish, which together are known as the cyclostomes or 'agnathans',
      are the only surviving lineages of jawless fish. They diverged early in
      vertebrate evolution, before the origin of the hinged jaws that are
      characteristic of gnathostome (jawed) vertebrates and before the evolution of
      paired appendages. However, they do share numerous characteristics with jawed
      vertebrates. Studies of cyclostome development can thus help us to understand
      when, and how, key aspects of the vertebrate body evolved. Here, we summarise the
      development of cyclostomes, highlighting the key species studied and experimental
      methods available. We then discuss how studies of cyclostomes have provided
      important insight into the evolution of fins, jaws, skeleton and neural crest.

PMID- 22619387
TI  - Drosophila primordial germ cell migration requires epithelial remodeling of the
      endoderm.
AB  - Trans-epithelial migration describes the ability of migrating cells to cross
      epithelial tissues and occurs during development, infection, inflammation, immune
      surveillance, wound healing and cancer metastasis. Here we investigate Drosophila
      primordial germ cells (PGCs), which migrate through the endodermal epithelium.
      Through live imaging and genetic experimentation we demonstrate that PGCs take
      advantage of endodermal tissue remodeling to gain access to the gonadal mesoderm
      and are unable to migrate through intact epithelial tissues. These results are in
      contrast to the behavior of leukocytes, which actively loosen epithelial
      junctions to migrate, and raise the possibility that in other contexts in which
      migrating cells appear to breach tissue barriers, they are actually exploiting
      existing tissue permeability. Therefore, the use of active invasive programs is
      not the sole mechanism to infiltrate tissues.

PMID- 22619388
TI  - Cellular retinoic acid-binding proteins are essential for hindbrain patterning
      and signal robustness in zebrafish.
AB  - The vitamin A derivative retinoic acid (RA) is a morphogen that patterns the
      anterior-posterior axis of the vertebrate hindbrain. Cellular retinoic acid
      binding proteins (Crabps) transport RA within cells to both its nuclear receptors
      (RARs) and degrading enzymes (Cyp26s). However, mice lacking Crabps are viable,
      suggesting that Crabp functions are redundant with those of other fatty acid
      binding proteins. Here we show that Crabps in zebrafish are essential for
      posterior patterning of the hindbrain and that they provide a key feedback
      mechanism that makes signaling robust as they are able to compensate for changes
      in RA production. Of the four zebrafish Crabps, Crabp2a is uniquely RA inducible
      and depletion or overexpression of Crabp2a makes embryos hypersensitive to
      exogenous RA. Computational models confirm that Crabp2a improves robustness
      within a narrow concentration range that optimizes a 'robustness index',
      integrating spatial information along the RA morphogen gradient. Exploration of
      signaling parameters in our models suggests that the ability of Crabp2a to
      transport RA to Cyp26 enzymes for degradation is a major factor in promoting
      robustness. These results demonstrate a previously unrecognized requirement for
      Crabps in RA signaling and hindbrain development, as well as a novel mechanism
      for stabilizing morphogen gradients despite genetic or environmental fluctuations
      in morphogen availability.

PMID- 22619390
TI  - The Polycomb group protein Ring1b is essential for pectoral fin development.
AB  - Polycomb group (PcG) proteins are transcriptional repressors that mediate
      epigenetic gene silencing by chromatin modification. PcG-mediated gene repression
      is implicated in development, cell differentiation, stem-cell fate maintenance
      and cancer. However, analysis of the roles of PcG proteins in orchestrating
      vertebrate developmental programs in vivo has been hampered by the early
      embryonic lethality of several PcG gene knockouts in mice. Here, we demonstrate
      that zebrafish Ring1b, the E3 ligase in Polycomb Repressive Complex 1 (PRC1), is
      essential for pectoral fin development. We show that differentiation of lateral
      plate mesoderm (LPM) cells into presumptive pectoral fin precursors is initiated
      normally in ring1b mutants, but fin bud outgrowth is impaired. Fgf signaling,
      which is essential for migration, proliferation and cell-fate maintenance during
      fin development, is not sufficiently activated in ring1b mutants. Exogenous
      application of FGF4, as well as enhanced stimulation of Fgf signaling by
      overactivated Wnt signaling in apc mutants, partially restores the fin
      developmental program. These results reveal that, in the absence of functional
      Ring1b, fin bud cells fail to execute the pectoral fin developmental program.
      Together, our results demonstrate that PcG-mediated gene regulation is essential
      for sustained Fgf signaling in vertebrate limb development.

PMID- 22619389
TI  - Dauer larva quiescence alters the circuitry of microRNA pathways regulating cell
      fate progression in C. elegans.
AB  - In C. elegans larvae, the execution of stage-specific developmental events is
      controlled by heterochronic genes, which include those encoding a set of
      transcription factors and the microRNAs that regulate the timing of their
      expression. Under adverse environmental conditions, developing larvae enter a
      stress-resistant, quiescent stage called 'dauer'. Dauer larvae are characterized
      by the arrest of all progenitor cell lineages at a stage equivalent to the end of
      the second larval stage (L2). If dauer larvae encounter conditions favorable for
      resumption of reproductive growth, they recover and complete development
      normally, indicating that post-dauer larvae possess mechanisms to accommodate an
      indefinite period of interrupted development. For cells to progress to L3 cell
      fate, the transcription factor Hunchback-like-1 (HBL-1) must be downregulated.
      Here, we describe a quiescence-induced shift in the repertoire of microRNAs that
      regulate HBL-1. During continuous development, HBL-1 downregulation (and
      consequent cell fate progression) relies chiefly on three let-7 family microRNAs,
      whereas after quiescence, HBL-1 is downregulated primarily by the lin-4 microRNA
      in combination with an altered set of let-7 family microRNAs. We propose that
      this shift in microRNA regulation of HBL-1 expression involves an enhancement of
      the activity of lin-4 and let-7 microRNAs by miRISC modulatory proteins,
      including NHL-2 and LIN-46. These results illustrate how the employment of
      alternative genetic regulatory pathways can provide for the robust progression of
      progenitor cell fates in the face of temporary developmental quiescence.

PMID- 22619392
TI  - Chemokine and Fgf signalling act as opposing guidance cues in formation of the
      lateral line primordium.
AB  - The directional migration of many cell populations occurs as a coherent group. An
      amenable model is provided by the posterior lateral line in zebrafish, which is
      formed by a cohesive primordium that migrates from head to tail and deposits
      future neuromasts at intervals. We found that prior to the onset of migration,
      the compact state of the primordium is not fully established, as isolated cells
      with lateral line identity are present caudal to the main primordium. These
      isolated cells are retained in position such that they fuse with the migrating
      primordium as it advances, and later contribute to the leading zone and terminal
      neuromasts. We found that the isolated lateral line cells are positioned by two
      antagonistic cues: Fgf signalling attracts them towards the primordium, which
      counteracts Sdf1alpha/Cxcr4b-mediated caudal attraction. These findings reveal a
      novel chemotactic role for Fgf signalling in which it enables the coalescence of
      the lateral line primordium from an initial fuzzy pattern into a compact group of
      migrating cells.

PMID- 22619391
TI  - UNC-4 antagonizes Wnt signaling to regulate synaptic choice in the C. elegans
      motor circuit.
AB  - Coordinated movement depends on the creation of synapses between specific neurons
      in the motor circuit. In C. elegans, this important decision is regulated by the
      UNC-4 homeodomain protein. unc-4 mutants are unable to execute backward
      locomotion because VA motor neurons are mis-wired with inputs normally reserved
      for their VB sisters. We have proposed that UNC-4 functions in VAs to block
      expression of VB genes. This model is substantiated by the finding that ectopic
      expression of the VB gene ceh-12 (encoding a homolog of the homeodomain protein
      HB9) in unc-4 mutants results in the mis-wiring of posterior VA motor neurons
      with VB-like connections. Here, we show that VA expression of CEH-12 depends on a
      nearby source of the Wnt protein EGL-20. Our results indicate that UNC-4 prevents
      VAs from responding to a local EGL-20 cue by disabling a canonical Wnt signaling
      cascade involving the Frizzled receptors MIG-1 and MOM-5. CEH-12 expression in VA
      motor neurons is also opposed by a separate pathway that includes the Wnt ligand
      LIN-44. This work has revealed a transcriptional mechanism for modulating the
      sensitivity of specific neurons to diffusible Wnt ligands and thereby defines
      distinct patterns of synaptic connectivity. The existence of comparable Wnt
      gradients in the vertebrate spinal cord could reflect similar roles for Wnt
      signaling in vertebrate motor circuit assembly.

PMID- 22619394
TI  - The effectiveness of substance use measures in the detection of full and partial
      denial of drug use.
AB  - Appraisals of substance abuse often constitute a key component of psychological
      assessments affecting both diagnostic and treatment issues. Because of negative
      consequences, many substance users engage in outright denials and marked
      minimization regarding their drug use. Psychological measures, especially those
      with transparent items, are highly vulnerable to this denial. To address this
      response style, indirect items are often included on substance use measures to
      identify those who deny their use. The purpose of this study was to examine the
      effects of complete and partial denial on the Drug Abuse Screening Test-20,
      Substance Abuse Subtle Screening Inventory-3, and Drug Use Screening Inventory
      Revised. Partial denial refers to the disacknowledgement of drug-related
      impairment interfering in multiple domains of a client's functioning. The study
      used a mixed within- and between-subjects design with 102 inpatient substance
      users. Each participant completed the study under two conditions: a disclosing
      condition and an experimental condition (either complete denial or partial
      denial). Results show partial denial is distinctly different from complete denial
      across three self-report substance use measures. Importantly, substance users
      engaging in these denial conditions were often undetected by these measures.
      Contrary to expectations, subtle scales with indirect item content were only
      minimally more effective than the face valid scales alone for the assessment of
      denied drug use. 

PMID- 22619393
TI  - Developing continuous variable composites for Rorschach measures of thought
      problems, vigilance, and suicide risk.
AB  - Using a multiple regression approach with a large developmental sample (N = 460)
      of Rorschach protocols from psychiatric, forensic, and nonclinical control
      groups, the authors created continuous multivariable Composite scores
      corresponding to the Comprehensive System (CS) Perceptual-Thinking Index,
      Hypervigilance Index, and Suicide Constellation. Within a validation sample (N =
      230), these three new scores, called the Thought and Perception Composite,
      Vigilance Composite, and Suicide Concern Composite were strongly associated with
      the three original CS Indices. Additional analyses suggest that the new Composite
      scores were more reliable than and at least as valid as the original Indices.
      Interpretive guidelines are offered. 

PMID- 22619395
TI  - Enhancing exposure and response prevention for OCD: a couple-based approach.
AB  - The effectiveness of individual therapy by exposure and response prevention (ERP)
      for obsessive-compulsive disorder (OCD) is well established, yet not all patients
      respond well, and some show relapse on discontinuation. This article begins by
      providing an overview of the personal and interpersonal experiences of OCD,
      focusing on interpersonal processes that maintain OCD symptoms and interfere with
      ERP. The study then describes a couple-based treatment program that the authors
      have developed to enhance ERP for individuals with OCD who are in long-term
      relationships. This program involves psychoeducation, partner-assisted exposure
      therapy, couple-based interventions aimed at changing maladaptive relationship
      patterns regarding OCD (i.e., symptom accommodation), and general couple therapy.
      Three case examples are presented to illustrate the couple-based techniques used
      in this treatment program.

PMID- 22619396
TI  - Context effects on habituation to disgust-relevant stimuli.
AB  - Although exposure-based treatments appear to be efficacious for the treatment of
      anxiety-related disorders, many individuals experience a renewal of the original
      fear response at follow-up. In an effort to prevent fear renewal, researchers
      have begun to use exposure of the conditioned stimulus in different contexts
      during extinction. Although studies continue to accumulate, showing that
      conducting exposure in multiple contexts buffers against the renewal of distress
      responses to fear-relevant stimuli, it remains unclear how conducting exposure in
      multiple contexts affects the renewal of distress responses to disgust-relevant
      stimuli. In the present study, participants (N = 52) were randomized to repeated
      presentations of disgust stimuli (vomiting in a toilet) in a single context or
      multiple contexts. Results revealed that those in the single context condition
      reported less distress after the exposure manipulation compared with the multiple
      context condition. Although there were no significant group differences in
      distress toward a novel disgust stimulus, the single context condition reported
      greater distress renewal than the multiple context condition. Furthermore,
      individuals in the multiple context condition showed significant reductions in
      distress at 1-week follow-up whereas distress in the single context condition
      remained stable. Subsequent analyses also provided moderate evidence for an
      effect of the disgust context manipulation on physiological arousal and disgust
      propensity, but not disgust-related behavioral avoidance. These findings offer
      preliminary evidence that renewal of distress toward disgust cues can be
      attenuated by conducting extinction in multiple contexts.

PMID- 22619397
TI  - Cue-elicited affect and craving: advancement of the conceptualization of craving
      in co-occurring posttraumatic stress disorder and alcohol dependence.
AB  - Posttraumatic stress disorder (PTSD) commonly co-occurs with alcohol dependence
      (AD) and negatively affects treatment outcomes. Trauma-related negative affect
      enhances substance craving in laboratory cue-reactivity studies of AD
      individuals, but the role of positive affect has not been established. In this
      study, 108 AD treatment-seeking adults with current PTSD and AD were presented
      with four counterbalanced trials consisting of an audio cue (personalized trauma
      or neutral script) followed by a beverage cue (alcohol or water). Results
      revealed alcohol cues increased positive and negative affect, and positive
      affective responses explained significant incremental variance in self-reported
      craving and salivation, but only when cues were accompanied by neutral not trauma
      imagery. Ambivalent (high negative and positive) responses were associated with
      strongest craving. Findings advance the conceptualization of craving in
      individuals with PTSD-AD and highlight the importance of independently assessing
      positive and negative affective responses to cues in individuals with co
      occurring PTSD-AD.

PMID- 22619398
TI  - Relation of red cell distribution width with presence and severity of coronary
      artery ectasia.
AB  - Red cell distribution width (RDW) is an index that has been shown to be an
      independent correlate of adverse outcomes in some cardiac conditions. Isolated
      coronary artery ectasia (CAE) is an abnormality of the coronary anatomy and can
      cause ischemia. We hypothesized that increased RDW would be associated with
      isolated CAE because both are associated with inflammation. In this study, 2345
      patients who received coronary angiography were retrospectively evaluated. After
      exclusion, 75 patients with isolated CAE and 96 consecutive patients with normal
      coronary were included in the study. The severity of isolated CAE was determined
      according to the Markis classification. Baseline RDW was measured as part of the
      automated complete blood count. Red cell distribution width was observed to be an
      independent predictor of both presence and severity of isolated CAE. In
      conclusion, RDW is associated with both the presence and severity of isolated
      CAE.

PMID- 22619399
TI  - Significance of screening electrocardiogram before the initiation of
      amitriptyline therapy in children with functional abdominal pain.
AB  - Amitriptyline (AMT) is commonly used in the management of children with irritable
      bowel syndrome. AMT is pro-arrhythmogenic and increases the risk of sudden
      cardiac death. However, there is not enough data regarding the cardiac toxicity
      in therapeutic doses of AMT in children and the need for screening
      electrocardiogram (EKG). Errors in computer EKG interpretation are not uncommon.
      In a risk-prevention study, the authors sought to identify the true incidence of
      prolonged corrected QT (QTc) interval and other arrhythmias in children with
      irritable bowel syndrome before the initiation of AMT. Out of the 760 EKGs
      screened, 3 EKGs demonstrated a true prolonged QTc after the careful manual
      reading by a pediatric cardiologist and they were not picked by computer
      generated reading. The authors conclude that screening EKG should always be
      performed on children before initiating AMT therapy. Also, the computer-generated
      EKG needs to be verified by a pediatric cardiologist to avoid serious
      misinterpretations.

PMID- 22619466
TI  - Current clinical development of PI3K pathway inhibitors in glioblastoma.
AB  - Glioblastoma (GBM) is the most common and lethal primary malignant tumor of the
      central nervous system, and effective therapeutic options are lacking. The
      phosphatidylinositol 3-kinase (PI3K) pathway is frequently dysregulated in many
      human cancers, including GBM. Agents inhibiting PI3K and its effectors have
      demonstrated preliminary activity in various tumor types and have the potential
      to change the clinical treatment landscape of patients with solid tumors. In this
      review, we describe the activation of the PI3K pathway in GBM, explore why
      inhibition of this pathway may be a compelling therapeutic target for this
      disease, and provide an update of the data on PI3K inhibitors in clinical trials
      and from earlier investigation.

PMID- 22619468
TI  - Prasugrel is effective and safe for neurointerventional procedures.
AB  - BACKGROUND: Clopidogrel bisulfate and aspirin are routinely administered as dual
      antiplatelet agents for many neurointerventional procedures, especially for
      intravascular stent placement. Many patients are non-responsive to clopidogrel,
      either secondary to drug interactions or from variations of cytochrome P450
      enzymes. Prasugrel (brand name Effient, Eli Lilly and Company, Indianapolis, IN,
      USA) is a new antiplatelet agent that has been utilized extensively in patients
      undergoing cardiovascular procedures but its safety and efficacy during
      neurointerventional procedures have not been evaluated. OBJECTIVE: To examine
      whether prasugrel is a safe and effective alternative to clopidogrel for
      neurointerventional procedures, especially in those patients who are either non
      responders or allergic to clopidogrel. METHODS: The medical records of all
      patients undergoing neurointerventional procedures at our institution who
      received prasugrel between January 2009 and July 2011 were retrospectively
      reviewed. A systematic chart review was performed and the following data were
      recorded: demographics, aneurysm location, endovascular techniques, peri- and
      post-procedural complications, hemorrhagic complications, clinical outcome and
      angiographic outcome. RESULTS: 16 patients undergoing neurointerventional
      procedures received prasugrel over a 2 year interval. All patients who had follow
      up studies of P2Y12 inhibition had immediate therapeutic response to prasugrel.
      There were no complications related to ischemic or intracranial hemorrhage.
      CONCLUSION: Prasugrel is a viable alternative to clopidogrel for patients
      undergoing neurointerventional procedures who are non-responders to clopidogrel.
      Further study is needed to evaluate the safety, efficacy and cost-effectiveness
      of prasugrel compared with clopidogrel for patients undergoing
      neurointerventional procedures.

PMID- 22619467
TI  - The hyperdense vessel sign on CT predicts successful recanalization with the
      Merci device in acute ischemic stroke.
AB  - BACKGROUND: The success of mechanical clot retrieval for acute ischemic stroke
      may be influenced by the characteristics of the occlusive thrombus. The thrombus
      can be partly characterized by CT, as the hyperdense vessel sign (HVS) suggests
      erythrocyte-rich clot whereas fibrin-rich clot may be isodense. We hypothesized
      that the physical clot characteristics that determine CT density may also
      determine likelihood of retrieval with the Merci device. METHODS: We reviewed all
      acute stroke cases initially imaged with non-contrast CT before attempted Merci
      clot retrieval at a single center between 2004 and 2010. Each CT was blindly
      assessed for the presence or absence of the HVS, and post-retrieval angiograms
      were blindly assessed for reperfusion using the TICI scale. RESULTS: Of 67
      patients analyzed (mean age 69; median NIHSS 19; 61% female), the HVS was seen in
      42, and no HVS was present in 25. Successful recanalization was achieved in 79%
      of patients with the HVS (33/42), but in only 36% (9/25) of patients without HVS
      (p=0.001). The HVS was the only significant predictor of recanalization while
      accounting for age, treatment with IV-tPA, clot location, stroke etiology, time
      to treatment, and number of retrieval attempts. CONCLUSION: The HVS in acute
      ischemic stroke was strongly predictive of successful recanalization using the
      Merci device. The HVS may indicate thrombi that are less adhesive compared with
      isodense clots that are more resistant to mechanical retrieval. The absence of
      HVS on pre-treatment CT may thus suggest the need for a more aggressive or
      alternative therapeutic approach.

PMID- 22619469
TI  - Vanishing aneurysm.

PMID- 22619470
TI  - Pathologic validation of clot length determined using thin section non-contrast
      CT.
AB  - BACKGROUND AND PURPOSE: Recent studies have demonstrated that in acute ischemic
      stroke patients, thin section non-contrast CT (NCCT) can be used to determine the
      length of the hyperdense intracranial thrombus, and that clot length using this
      approach predicts the likelihood of vessel recanalization after intravenous
      tissue plasminogen activator. SUMMARY OF CASE: An acute ischemic stroke patient
      presented with a left middle cerebral artery occlusion and underwent emergent
      catheter based therapy. Clot length was determined using pretreatment thin
      section NCCT and was independently confirmed by the pathologist after whole clot
      extraction. CONCLUSIONS: The concordance between the NCCT measured clot length
      and the pathological examination in this case provides additional support for the
      accuracy of using thin section NCCT data to determine clot length in all
      patients.

PMID- 22619472
TI  - Leaf adaxial-abaxial polarity specification and lamina outgrowth: evolution and
      development.
AB  - A key innovation in leaf evolution is the acquisition of a flat lamina with
      adaxial-abaxial polarity, which optimizes the primary function of photosynthesis.
      The developmental mechanism behind leaf adaxial-abaxial polarity specification
      and flat lamina formation has long been of interest to biologists. Surgical and
      genetic studies proposed a conceptual model wherein a signal derived from the
      shoot apical meristem is necessary for adaxial-abaxial polarity specification,
      and subsequent lamina outgrowth is promoted at the juxtaposition of adaxial and
      abaxial identities. Several distinct regulators involved in leaf adaxial-abaxial
      polarity specification and lamina outgrowth have been identified. Analyses of
      these genes demonstrated that the mutual antagonistic interactions between
      adaxial and abaxial determinants establish polarity and define the boundary
      between two domains, along which lamina outgrowth regulators function.
      Evolutionary developmental studies on diverse leaf forms of angiosperms proposed
      that alteration to the adaxial-abaxial patterning system can be a major driving
      force in the generation of diverse leaf forms, as represented by 'unifacial
      leaves', in which leaf blades have only the abaxial identity. Interestingly,
      unifacial leaf blades become flattened, in spite of the lack of adaxial-abaxial
      juxtaposition. Modification of the adaxial-abaxial patterning system is also
      utilized to generate complex organ morphologies, such as stamens. In this review,
      we summarize recent advances in the genetic mechanisms underlying leaf adaxial
      abaxial polarity specification and lamina outgrowth, with emphasis on the genetic
      basis of the evolution and diversification of leaves.

PMID- 22619471
TI  - Regulation of leaf morphology by microRNA394 and its target LEAF CURLING
      RESPONSIVENESS.
AB  - The present study identified Arabidopsis miR394 and its target, an F-box (SKP1
      Cullin/CDC53-F-box) gene At1g27340 (here referred to as LEAF CURLING
      RESPONSIVENESS, LCR), for regulation of leaf curling-related morphology. The loss
      of-function lcr mutants exhibit pleiotropic defects with semi-dwarfism, altered
      leaf shape and a shorter stem. Overexpression of an miR394-resistant version of
      LCR under the 35S promoter (35S:m5LCR) and target mimicry MIM394 resulted in a
      curled-down leaf defect. Conversely, transgenic plants overexpressing
      35S:MIR394a/b display a curled-up leaf phenotype. Detailed analyses show that
      there is a certain level of LCR that is optimal for leaf morphology, but lower or
      higher levels lead to abnormal leaf development, indicating that expression of
      miR394 in the leaf lamina is necessary for proper leaf morphology. Because the
      phytohormone auxin plays a crucial role in leaf morphogenesis and patterning, the
      DR5-GUS reporter gene was used to monitor the auxin response. We show that DR5
      expression patterns in lcr and 35S::m5LCR plants were significantly different
      from those in the wild type. Also, overexpression of LCR in 35S::m5LCR plants
      drastically decreased the expression of the auxin-responsive genes IAA3, AXR3 and
      IAMT1, whereas increased expression of the genes was found in 35S::MIR394a
      plants. These results indicate that miR394 and its target LCR are involved in the
      regulation of leaf development.

PMID- 22619473
TI  - Planning a pharmacy-led medical mission trip, part 2: servant leadership and team
      dynamics.
AB  - While pharmacy curricula can prepare students for the cognitive domains of
      pharmacy practice, mastery of the affective aspects can prove to be more
      challenging. At the Gregory School of Pharmacy, medical mission trips have been
      highly effective means of impacting student attitudes and beliefs. Specifically,
      these trips have led to transformational changes in student leadership capacity,
      turning an act of service into an act of influence. Additionally, building team
      unity is invaluable to the overall effectiveness of the trip. Pre-trip
      preparation for teams includes activities such as routine team meetings, team
      building activities, and implementation of committees, as a means of promoting
      positive team dynamics. While in the field, team dynamics can be fostered through
      activities such as daily debriefing sessions, team disclosure times, and
      provision of medical services.

PMID- 22619474
TI  - Sylatron: a pegylated interferon for use in melanoma.
AB  - OBJECTIVE: To review the currently available literature on peginterferon alfa-2b
      (pegIFN [Sylatron]), including its role in therapy and toxicity for adjuvant
      treatment of locally advanced melanoma. DATA SOURCES: A literature search was
      performed of PubMed and the American Society of Clinical Oncology abstracts from
      1976 to February 2012, using the primary search terms peginterferon alfa-2b,
      interferon, Sylatron, and melanoma. STUDY SELECTION AND DATA EXTRACTION: All
      available English-language articles and trials that described the pharmacology,
      pharmacokinetics, pharmacodynamics, clinical activity, or safety profile of
      pegIFN were reviewed. DATA SYNTHESIS: PegIFN was approved in March 2011 for the
      adjuvant treatment of node-positive melanoma. Interferon (IFN) is commonly used
      in patients with melanoma who remain at high risk for relapse following surgery;
      however, the optimal scheduling and dose are not agreed upon. Pegylation of IFN
      involves conjugation with polyethylene glycol. Following subcutaneous injection
      of pegIFN, the rate of absorption, renal and cellular clearance, and
      immunogenicity are reduced. As a result of the extended serum half-life, once
      weekly administration is feasible, compared with the daily and/or thrice weekly
      dosing of IFN. When compared with observation alone in patients with resected
      stage III melanoma, pegIFN demonstrated a significant increase in relapse-free
      survival, with a marginal impact on overall survival. The most common adverse
      events were as expected with IFN and included fatigue, increased liver enzymes,
      pyrexia, headache, anorexia, myalgia, nausea, chills, depression, and injection
      site reactions. A large Phase 3 study is underway to further assess outcome and
      toxicity differences between pegIFN weekly and low-dose IFN thrice weekly.
      CONCLUSIONS: PegIFN is a modified version of the previously approved interferon
      indicated for the adjuvant treatment of melanoma. Although the safety profile
      remains similar between the pegylated and non-pegylated forms, once-weekly
      administration is feasible secondary to an extended serum half-life and may have
      improved convenience for the patient.

PMID- 22619475
TI  - Use of oral vitamin K for prevention of late vitamin k deficiency bleeding in
      neonates when injectable vitamin K is not available.
AB  - OBJECTIVE: To evaluate the literature describing use of oral vitamin K(1)
      (phytonadione) to prevent late vitamin K deficiency bleeding (VKDB) in neonates
      when injectable vitamin K preparations are not available. DATA SOURCES: Articles
      were retrieved through MEDLINE (1946-February 2012) using the terms vitamin K,
      vitamin K deficiency bleeding, newborn, neonate, and prophylaxis. Reference
      citations from publications identified were reviewed. STUDY SELECTION AND DATA
      EXTRACTION: All articles published in English on the use of prophylactic oral
      vitamin K in neonates were evaluated. The largest epidemiologic studies
      discussing the efficacy of continuous oral vitamin K prophylaxis were reviewed.
      Individual, smaller clinical trials were not reviewed. DATA SYNTHESIS: For
      prevention of early, classic, and late VKDB, use of intramuscular vitamin K 1 mg
      is preferred over oral administration because of superior efficacy. Single oral
      doses protect against early VKDB, but multiple oral doses are needed for late
      VKDB prophylaxis, especially in exclusively breast-fed neonates. Continuous oral
      dosing regimens used in the literature vary; European epidemiologic data suggest
      the lowest rates of late VKDB with oral vitamin K 1 mg at birth followed by 25
      MUg daily for 13 weeks, or 2 mg at birth followed by 1 mg weekly for 3 months.
      Limited data describe the use of oral prophylactic vitamin K in high-risk
      patients (eg, premature neonates, biliary abnormalities). CONCLUSIONS: While
      there are data supporting effective oral vitamin K dosing regimens for prevention
      of late VKBD in exclusively breast-fed neonates, lack of an appropriate oral
      dosage form prevents routine use of this technique in the US. In times of drug
      shortage, injectable vitamin K preparations should be reserved for use in
      neonates. If injectable vitamin K is not available, clinicians should choose the
      most practical method of administering oral vitamin K based on the oral products
      available.

PMID- 22619476
TI  - Successful treatment of polymicrobial calcaneal osteomyelitis with telavancin,
      rifampin, and meropenem.
AB  - OBJECTIVE: To report a case of multidrug-resistant osteomyelitis successfully
      treated with telavancin, rifampin, and meropenem. CASE SUMMARY: An 18-year-old
      male with spina bifida was treated primarily in the outpatient setting over the
      course of 133 days with multiple antimicrobials for a recurrent right calcaneal
      wound and osteomyelitis infection. Initial cultures were positive for methicillin
      resistant Staphylococcus aureus and coagulase-negative Staphylococcus, which were
      treated with intravenous vancomycin 1 g every 12 hours, increased after 13 days
      to 1.5 g every 12 hours with addition of rifampin 300 mg twice daily, both of
      which were discontinued on day 22 due to leukopenia (white blood cell count 3.0 *
      10(3)/MUL) and neutropenia (absolute neutrophil count 0.2 * 10(3)/MUL).
      Daptomycin 8 mg/kg/day was then initiated with rifampin 300 mg twice daily;
      treatment was discontinued after 49 days due to an elevated creatine kinase level
      of 1831 U/L (baseline 86). Intravenous meropenem 1 g every 8 hours was again
      initiated on day 83 following additional identification of quinolone-resistant
      Pseudomonas aeruginosa from the soft tissue of the right foot. Intravenous
      vancomycin 1 g every 12 hours was also restarted at this time for persistent
      coagulase-negative Staphylococcus and oral rifampin 300 mg twice daily was again
      added. Adverse events again required the discontinuation of vancomycin on day 91.
      The eventual drug therapy regimen consisted of telavancin 750 mg/day for 42 days,
      meropenem for 50 days, and oral rifampin for 50 days. At the end of treatment,
      the patient's right heel wound had almost completely closed. He was without
      recurrence or treatment-related adverse events at follow-up 1 year later.
      DISCUSSION: Antimicrobial selection for osteomyelitis infections presents a
      challenge to the clinician due to patient intolerance, increasing antimicrobial
      resistance, and variable antimicrobial penetration at the site of infection. To
      our knowledge, this is the first case report of the successful use of a regimen
      including telavancin for the treatment of a recurrent, coagulase-negative
      Staphylococcus osteomyelitis infection. CONCLUSIONS: In this complex case
      involving a polymicrobial infection of the right calcaneal bone and surrounding
      soft tissue, eventual drug therapy including telavancin, meropenem, and rifampin
      resulted in a successful clinical response.

PMID- 22619477
TI  - Eribulin: a novel cytotoxic chemotherapy agent.
AB  - OBJECTIVE: To review the chemistry, pharmacology, pharmacokinetics, safety, and
      efficacy of eribulin (Halaven). DATA SOURCES: A literature search (up to December
      2011) using the terms eribulin, Halaven, ER-086526, and E7389 was performed with
      PubMed, Google Scholar, selected Ovid bibliography searches, and the abstract
      search tool from the American Society of Clinical Oncology Annual Meetings and
      the San Antonio Breast Cancer Symposia. Additional references from the
      bibliographies of these articles were also assessed. DATA EXTRACTION: English
      language preclinical and clinical studies on the chemistry, pharmacology,
      pharmacokinetics, safety, and efficacy of eribulin were reviewed. DATA SYNTHESIS:
      Eribulin is a novel microtubule inhibitor with a unique mechanism of action,
      which involves interaction with a distinct binding site on beta-tubulin leading
      to G(2)/M phase cell-cycle arrest and apoptosis. Eribulin has been approved by
      the Food and Drug Administration for the treatment of metastatic breast cancer in
      patients who have been previously treated with an anthracycline and a taxane. In
      a pivotal Phase 3 study conducted in patients with metastatic breast cancer,
      eribulin 1.4 mg/m(2), administered over 2-5 minutes as an intravenous infusion on
      days 1 and 8 of 21-day cycles, was associated with a significantly increased
      median overall survival of 13.1 months compared to the median overall survival of
      10.6 months in the therapy of physician's choice. Eribulin has also shown
      activity in Phase 2 studies in other types of cancers, such as non-small cell
      lung cancer, prostate cancer, urothelial cancer, soft tissue sarcomas, and
      platinum-susceptible ovarian, fallopian tube, or peritoneal cancers. The most
      severe (grade 3/4) adverse effects associated with eribulin include neutropenia,
      leukopenia, and peripheral neuropathy. Common toxicities include fatigue,
      neutropenia, alopecia, anemia, and peripheral neuropathy. CONCLUSIONS: Eribulin
      is a promising new cytotoxic chemotherapy agent due to its ability to treat
      cancers that are refractory or resistant to other drugs as well as its manageable
      toxicity profile.

PMID- 22619479
TI  - Biliary leak in post-liver-transplant patients: is there any place for metal
      stent?
AB  - Objectives. Endoscopic management of bile leak after orthotopic liver transplant
      (OLT) is widely accepted. Preliminary studies demonstrated encouraging results
      for covered self-expandable metal stents (CSEMS) in complex bile leaks. Methods.
      Thirty-one patients with post-OLT bile leaks underwent endoscopic temporary
      placement of CSEMS (3 partially CSEMS , 18 fully CSEMS with fins and 10 fully
      CSEMS with flare ends) between December 2003 and December 2010. Long-term
      clinical success and safety were evaluated. Results. Median stent indwelling and
      follow-up were 89 and 1,353 days for PCSEMS, 102 and 849 for FCSEMS with fins and
      98 and 203 for FCSEMS with flare ends. Clinical success was achieved in 100%,
      77.8%, and 70%, respectively. Postplacement complications: cholangitis (1) and
      proximal migration (1), both in the FCSEMS with fins. Postremoval complications
      were biliary strictures requiring drainage: PCSEMS (1), FCSEMS with fins (6) and
      with flare ends (1). There was no significant differences in the FCSEMS groups
      regarding clinical success, age, gender, leak location, previous treatment, stent
      indwelling, and complications. Conclusion. Temporary placement of CSEMS is
      effective to treat post-OLT biliary leaks. However, a high number of post removal
      biliary strictures occurred especially in the FCSEMS with fins. CSEMS cannot be
      recommended in this patient population.

PMID- 22619480
TI  - L-arginine and asymmetric dimethylarginine are early predictors for survival in
      septic patients with acute liver failure.
AB  - Dysfunctions of the L-arginine (L-arg)/nitric-oxide (NO) pathway are suspected to
      be important for the pathogenesis of multiple organ dysfunction syndrome (MODS)
      in septic shock. Therefore plasma concentrations of L-arg and asymmetric
      dimethylarginine (ADMA) were measured in 60 patients with septic shock, 30
      surgical patients and 30 healthy volunteers using enzyme linked immunosorbent
      assay (ELISA) kits. Plasma samples from patients with septic shock were collected
      at sepsis onset, and 24 h, 4 d, 7 d, 14 d and 28 d later. Samples from surgical
      patients were collected prior to surgery, immediately after the end of the
      surgical procedure as well as 24 h later and from healthy volunteers once. In
      comparison to healthy volunteers and surgical patients, individuals with septic
      shock showed significantly increased levels of ADMA, as well as a decrease in the
      ratio of L-arg and ADMA at all timepoints. In septic patients with an acute liver
      failure (ALF), plasma levels of ADMA and L-arg were significantly increased in
      comparison to septic patients with an intact hepatic function. In summary it can
      be stated, that bioavailability of NO is reduced in septic shock. Moreover,
      measurements of ADMA and L-arg appear to be early predictors for survival in
      patients with sepsis-associated ALF.

PMID- 22619481
TI  - Mast cell-mediated inhibition of abdominal neutrophil inflammation by a PEGylated
      TLR7 ligand.
AB  - Although the mechanisms for sustained chemokine gradients and recurring cell
      infiltration in sterile peritonitis have not been elucidated, toll-like receptors
      (TLRs) have been implicated. To abate the deleterious recruitment of neutrophils
      in sterile inflammation, we repeatedly administered a TLR7 ligand that
      hyposensitized to TLR7 and receptors that converged on the MyD88-signaling
      intermediary and reduced cellular infiltration in murine autoimmune models of
      multiple sclerosis and arthritis. To reduce potential adverse effects, a
      polyethylene glycol polymer was covalently attached to the parent compound
      (Tolerimod1). The proinflammatory potency of Tolerimod1 was 10-fold less than the
      unconjugated TLR7 ligand, and Tolerimod1 reduced neutrophil recruitment in
      chemically induced peritonitis and colitis. The effects of Tolerimod1 were
      mediated by the radioresistant cells in radiation chimeric mice and by mast cells
      in reconstituted mast cell-deficient mice (Kit(W-sh)). Although the Tolerimod1
      had weak proinflammatory agonist activity, it effectively reduced neutrophil
      recruitment in sterile peritoneal inflammation.

PMID- 22619482
TI  - oxLDL downregulates the dendritic cell homing factors CCR7 and CCL21.
AB  - INTRODUCTION: Dendritic cells (DCs) and oxLDL play an important role in the
      atherosclerotic process with DCs accumulating in the plaques during plaque
      progression. Our aim was to investigate the role of oxLDL in the modulation of
      the DC homing-receptor CCR7 and endothelial-ligand CCL21. METHODS AND RESULTS:
      The expression of the DC homing-receptor CCR7 and its endothelial-ligand CCL21
      was examined on atherosclerotic carotic plaques of 47 patients via qRT-PCR and
      immunofluorescence. In vitro, we studied the expression of CCR7 on DCs and CCL21
      on human microvascular endothelial cells (HMECs) in response to oxLDL. CCL21- and
      CCR7-mRNA levels were significantly downregulated in atherosclerotic plaques
      versus non-atherosclerotic controls [90% for CCL21 and 81% for CCR7 (P < 0.01)].
      In vitro, oxLDL reduced CCR7 mRNA levels on DCs by 30% and protein levels by 46%.
      Furthermore, mRNA expression of CCL21 was significantly reduced by 50% (P < 0.05)
      and protein expression by 24% in HMECs by oxLDL (P < 0.05). CONCLUSIONS: The
      accumulation of DCs in atherosclerotic plaques appears to be related to a
      downregulation of chemokines and their ligands, which are known to regulate DC
      migration. oxLDL induces an in vitro downregulation of CCR7 and CCL21, which may
      play a role in the reduction of DC migration from the plaques.

PMID- 22619483
TI  - Lipid bodies: inflammatory organelles implicated in host-Trypanosoma cruzi
      interplay during innate immune responses.
AB  - The flagellated protozoa Trypanosoma cruzi is the causal agent of Chagas'
      disease, a significant public health issue and still a major cause of morbidity
      and mortality in Latin America. Acute Chagas' disease elicits a strong
      inflammatory response. In order to control the parasite multiplication, cells of
      the monocytic lineage are highly mobilized. Monocyte differentiation leads to the
      formation of phagocytosing macrophages, which are strongly activated and direct
      host defense. A distinguishing feature of Chagas' disease-triggered macrophages
      is the presence of increased numbers of distinct cytoplasmic organelles termed
      lipid bodies or lipid droplets. These organelles are actively formed in response
      to the parasite and are sites for synthesis and storage of inflammatory
      mediators. This review covers current knowledge on lipid bodies elicited by the
      acute Chagas' disease within inflammatory macrophages and discusses the role of
      these organelles in inflammation. The increased knowledge of lipid bodies in
      pathogenic mechanisms of infections may not only contribute to the understanding
      of pathogen-host interactions but may also identify new targets for intervention.

PMID- 22619484
TI  - NFAT5 contributes to osmolality-induced MCP-1 expression in mesothelial cells.
AB  - Increased expression of the C-C chemokine monocyte chemoattractant protein-1 (MCP
      1) in mesothelial cells in response to high glucose concentrations and/or high
      osmolality plays a crucial role in the development of peritoneal fibrosis during
      continuous ambulatory peritoneal dialysis (CAPD). Recent studies suggest that in
      kidney cells osmolality-induced MCP-1 upregulation is mediated by the
      osmosensitive transcription factor, nuclear factor of activated T cells 5
      (NFAT5). The present study addressed the question of whether activation of NFAT5
      by hyperosmolality, as present in PD fluids, contributes to MCP-1 expression in
      the mesothelial cell line Met5A. Hyperosmolality, induced by addition of glucose,
      NaCl, or mannitol to the growth medium, increased NFAT5 activity and stimulated
      MCP-1 expression in Met5A cells. siRNA-mediated knockdown of NFAT5 attenuated
      osmolality-induced MCP-1 upregulation substantially. Hyperosmolality also induced
      activation of nuclear factor-kappaB (NF-kappaB). Accordingly, pharmacological
      inhibition of NF-kappaB significantly decreased osmolality-induced MCP-1
      expression. Taken together, these results indicate that high osmolalities
      activate the transcription factor NFAT5 in mesothelial cells. NFAT5 in turn
      upregulates MCP-1, likely in combination with NF-kappaB, and thus may participate
      in the development of peritoneal fibrosis during CAPD.

PMID- 22619485
TI  - The PBDE-209 exposure during pregnancy and lactation impairs immune function in
      rats.
AB  - In the present study, we assessed the treatment effects of PBDE-209
      administration on the immune function in rats during pregnancy and lactation. We
      harvested the blood and organs for flow cytometry, viability assay, enzyme-linked
      immunosorbent assay, and histological evaluation. The results of this study were
      the PBDE-209 exposure during pregnancy and lactation impairs immune function in
      rats. The results may contribute to understanding the mechanism of PBDE-209 in
      immune function.

PMID- 22619486
TI  - Sclerosing peritonitis: a rare but fatal complication of peritoneal inflammation.
AB  - Sclerosing peritonitis is a rare form of peritoneal inflammation with an often
      fatal outcome. The major risk factor of sclerosing peritonitis is peritoneal
      dialysis treatment but it can also occur following renal or liver transplantation
      or be associated with certain drug treatment. This article gives an overview of
      reasons and treatment options for sclerosing peritonitis and shows a summery of
      current literature about sclerosing peritonitis.

PMID- 22619487
TI  - Pregnancy followed by delivery may affect circulating soluble lectin-like
      oxidized low-density lipoprotein receptor-1 levels in women of reproductive age.
AB  - BACKGROUND/OBJECTIVE: It is known that menopause or lack of endogenous estrogen
      is a risk factor for endothelial dysfunction and CAD. Lectin-like oxidized low
      density lipoprotein receptor-1 (LOX-1) is involved inmultiple phases of vascular
      dysfunction. The purpose of the current study was to determine the association
      between soluble LOX-1 (sLOX-1) and pregnancy followed by delivery in women of
      reproductive age. MATERIALS/METHODS: Sixty-eight subjects with pregnancy followed
      by delivery (group 1) and 57 subjects with nongravidity (group 2) were included
      in this study. Levels of sLOX-1 were measured in serum by EL SA. RESULTS: Plasma
      levels of sLOX-1 were significantly lower in Group 1 than Group 2 in women of
      reproductive age (0.52 +/- 0.18 ng/mL and 0.78 +/- 0.13, resp., P < 0.001). There
      were strong correlations between sLOX-1 levels and the number of gravida (r = 
      0.645, P < 0.001). The levels of sLOX-1 highly correlated with the number of
      parous (r = -0.683, P < 0.001). CONCLUSION: Our study demonstrated that serum
      sLOX-1 levels were associated with pregnancy followed by delivery that might
      predict endothelial dysfunction. We conclude that pregnancy followed by delivery
      may delay the beginning and progress of arteriosclerosis and its clinical
      manifestations in women of reproductive age.

PMID- 22619488
TI  - Cytotoxic T lymphocytes and vaccine development 2011.

PMID- 22619489
TI  - Animal model of dermatophytosis.
AB  - Dermatophytosis is superficial fungal infection caused by dermatophytes that
      invade the keratinized tissue of humans and animals. Lesions from dermatophytosis
      exhibit an inflammatory reaction induced to eliminate the invading fungi by using
      the host's normal immune function. Many scientists have attempted to establish an
      experimental animal model to elucidate the pathogenesis of human dermatophytosis
      and evaluate drug efficacy. However, current animal models have several issues.
      In the present paper, we surveyed reports about the methodology of the
      dermatophytosis animal model for tinea corporis, tinea pedis, and tinea unguium
      and discussed future prospects.

PMID- 22619490
TI  - Effect of low tube voltage on image quality, radiation dose, and low-contrast
      detectability at abdominal multidetector CT: phantom study.
AB  - PURPOSE: To investigate the effect of low tube voltage (80 kV) on image quality,
      radiation dose, and low-contrast detectability (LCD) at abdominal computed
      tomography (CT). MATERIALS AND METHODS: A phantom containing low-contrast objects
      was scanned with a CT scanner at 80 and 120 kV, with tube current-time product
      settings at 150-650 mAs. The differences between image noise, contrast-to-noise
      ratio (CNR), and scores of LCD obtained with 80 kV at 150-650 mAs and those
      obtained with 120 kV at 300 mAs were compared respectively. RESULTS: The image
      noise substantially increased with low tube voltage. However, with identical
      dose, use of 80 kV resulted in higher CNR compared with CNR at 120 kV. There were
      no statistically significant difference in CNR and scores of LCD between 120 kV
      at 300 mAs and 80 kV at 550-650 mAs (P > 0.05). The relative dose delivered at 80
      kV ranged from 58% at 550 mAs to 68% at 650 mAs. CONCLUSION: With a reduction of
      the tube voltage from 120 kV to 80 kV at abdominal CT, the radiation dose can be
      reduced by 32% to 42% without degradation of CNR and LCD.

PMID- 22619491
TI  - Neurodevelopment of Amazonian infants: antenatal and postnatal exposure to methyl
      and ethylmercury.
AB  - Neurodevelopment as Gesell development scores (GDSs) in relation to mercury
      exposure in infants (<6 months of age) of one urban center and two rural
      villages, respectively, of fisherman and cassiterite miners. Mean total hair-Hg
      (HHg) concentrations of infants from Itapua (3.95 +/- 1.8 ppm) were statistically
      (P = 0.0001) different from those of infants from Porto Velho (3.84 +/- 5.5 ppm)
      and Bom Futuro (1.85 +/- 0.9 ppm). Differences in vaccine coverage among these
      populations resulted in significantly higher (P = 0.0001) mean ethylmercury
      (EtHg) exposure in urban infants (150 MUg) than in infants from either village
      (41.67 MUg, Itapua; 42.39 MUg, Bom Futuro). There was an inverse significant
      (Spearman r = -0.2300; P = 0.0376) correlation between HHg and GDS for infants
      from Porto Velho, but not for the rural infants from Bom Futuro (Spearman r =
      0.1336; P = 0.0862) and Itapua (Spearman r = 0.1666; P = 0.5182). Logistic
      regression applied to variables above or below the median GDS showed that EtHg
      exposure (estimated probability = -0.0157; P = 0.0070) and breastfeeding score
      (estimated probability = -0.0066; P = 0.0536) score were significantly associated
      with GDS. Conclusion. In nurslings whose mothers are exposed to different levels
      of fish-MeHg (HHg), a higher score of neurological development at six months was
      negatively associated with exposure to additional TCV-EtHg. Results should be
      interpreted with caution because of unaccounted variables.

PMID- 22619492
TI  - Using hierarchical time series clustering algorithm and wavelet classifier for
      biometric voice classification.
AB  - Voice biometrics has a long history in biosecurity applications such as
      verification and identification based on characteristics of the human voice. The
      other application called voice classification which has its important role in
      grouping unlabelled voice samples, however, has not been widely studied in
      research. Lately voice classification is found useful in phone monitoring,
      classifying speakers' gender, ethnicity and emotion states, and so forth. In this
      paper, a collection of computational algorithms are proposed to support voice
      classification; the algorithms are a combination of hierarchical clustering,
      dynamic time wrap transform, discrete wavelet transform, and decision tree. The
      proposed algorithms are relatively more transparent and interpretable than the
      existing ones, though many techniques such as Artificial Neural Networks, Support
      Vector Machine, and Hidden Markov Model (which inherently function like a black
      box) have been applied for voice verification and voice identification. Two
      datasets, one that is generated synthetically and the other one empirically
      collected from past voice recognition experiment, are used to verify and
      demonstrate the effectiveness of our proposed voice classification algorithm.

PMID- 22619493
TI  - Toward a blended ontology: applying knowledge systems to compare therapeutic and
      toxicological nanoscale domains.
AB  - Bionanomedicine and environmental research share need common terms and
      ontologies. This study applied knowledge systems, data mining, and bibliometrics
      used in nano-scale ADME research from 1991 to 2011. The prominence of nano-ADME
      in environmental research began to exceed the publication rate in medical
      research in 2006. That trend appears to continue as a result of the growing
      products in commerce using nanotechnology, that is, 5-fold growth in number of
      countries with nanomaterials research centers. Funding for this research
      virtually did not exist prior to 2002, whereas today both medical and
      environmental research is funded globally. Key nanoparticle research began with
      pharmacology and therapeutic drug-delivery and contrasting agents, but the
      advances have found utility in the environmental research community. As evidence
      ultrafine aerosols and aquatic colloids research increased 6-fold, indicating a
      new emphasis on environmental nanotoxicology. User-directed expert elicitation
      from the engineering and chemical/ADME domains can be combined with appropriate
      Boolean logic and queries to define the corpus of nanoparticle interest. The
      study combined pharmacological expertise and informatics to identify the corpus
      by building logical conclusions and observations. Publication records informatics
      can lead to an enhanced understanding the connectivity between fields, as well as
      overcoming the differences in ontology between the fields.

PMID- 22619494
TI  - Factors of the lectin pathway of complement activation and their clinical
      associations in neonates.
AB  - This paper summarizes the data concerning soluble defense lectins (mannan-binding
      lectin, M-ficolin, L-ficolin, and H-ficolin) with the unique ability to activate
      complement and their associated serine proteases (MASPs) in neonates. The
      clinical importance of deficiencies of these immune factors is presented in
      aspects of perinatal mortality, premature births, and low birthweight. Prenatal
      serum concentrations of L-ficolin, H-ficolin, and MASP-2 (and probably M-ficolin)
      correlate with gestational age and birthweight. The relationship of serum MBL to
      gestational age is controversial. The MBL2 genotypes XA/O and O/O (associated
      with low-serum MBL) are associated with perinatal infections, whereas the high
      serum MBL-conferring A/A genotypes may be associated with prematurity. Low-serum
      L-ficolin concentrations, but not low-serum H-ficolin concentrations, are also
      associated with perinatal infections. Much of the literature is inconsistent, and
      the relationships reported so far require independent confirmation at both gene
      and protein levels. Our preliminary conclusion is that these soluble defense
      lectins play a protective role in the neonate, and that insufficiency of such
      factors contributes to the adverse consequences of prematurity and low
      birthweight.

PMID- 22619495
TI  - Effect of heat exposure on gene expression of feed intake regulatory peptides in
      laying hens.
AB  - The aim of this paper was to investigate the effect of heat stress on the
      regulation of appetite-associated genes in laying hens. Forty eight laying hens
      were randomly divided into two circumstances: high (31 +/- 1.5 degrees C;
      relative humidity, 82.0 +/- 2.2%) or normal (20 +/- 2 degrees C, control;
      relative humidity, 60.1 +/- 4.5%) ambient environment. Heat stress decreased body
      weight gain (P < 0.01), feed intake (P < 0.01), laying rate (P < 0.05), average
      egg mass (P < 0.01), egg production (P < 0.01), shell thickness (P < 0.01), and
      feed efficiency (P < 0.05). High ambient temperature decreased plasma uric acid
      (P < 0.05). Heat stress significantly increased mRNA levels of ghrelin and
      cocaine- and amphetamine-regulated transcript (P < 0.05) and decreased mRNA
      levels of cholecystokinin (P < 0.05) in the hypothalamus. Heat stress
      significantly increased (P < 0.05) mRNA levels of ghrelin in the glandular
      stomach and jejunum but significantly decreased (P < 0.05) mRNA levels of
      cholecystokinin in the duodenum and jejunum. In conclusion, heat stress plays a
      unique role in some special neuropeptides (e.g., ghrelin, cocaine- and
      amphetamine-regulated transcript, and cholecystokinin), which might participate
      in the regulation of feed intake in laying hens under high ambient temperature.

PMID- 22619496
TI  - Proteomic characterization of a mouse model of familial Danish dementia.
AB  - A dominant mutation in the ITM2B/BRI2 gene causes familial Danish dementia (FDD)
      in humans. To model FDD in animal systems, a knock-in approach was recently
      implemented in mice expressing a wild-type and mutant allele, which bears the FDD
      associated mutation. Since these FDD(KI) mice show behavioural alterations and
      impaired synaptic function, we characterized their synaptosomal proteome via two
      dimensional differential in-gel electrophoresis. After identification by
      nanoliquid chromatography coupled to electrospray-linear ion trap tandem mass
      spectrometry, the differentially expressed proteins were classified according to
      their gene ontology descriptions and their predicted functional interactions. The
      Dlg4/Psd95 scaffold protein and additional signalling proteins, including protein
      phosphatases, were revealed by STRING analysis as potential players in the
      altered synaptic function of FDD(KI) mice. Immunoblotting analysis finally
      demonstrated the actual downregulation of the synaptosomal scaffold protein
      Dlg4/Psd95 and of the dual-specificity phosphatase Dusp3 in the synaptosomes of
      FDD(KI) mice.

PMID- 22619497
TI  - MicroRNAs and induced pluripotent stem cells for human disease mouse modeling.
AB  - Human disease animal models are absolutely invaluable tools for our understanding
      of mechanisms involved in both physiological and pathological processes. By
      studying various genetic abnormalities in these organisms we can get a better
      insight into potential candidate genes responsible for human disease development.
      To this point a mouse represents one of the most used and convenient species for
      human disease modeling. Hundreds if not thousands of inbred, congenic, and
      transgenic mouse models have been created and are now extensively utilized in the
      research labs worldwide. Importantly, pluripotent stem cells play a significant
      role in developing new genetically engineered mice with the desired human disease
      like phenotype. Induced pluripotent stem (iPS) cells which represent
      reprogramming of somatic cells into pluripotent stem cells represent a
      significant advancement in research armament. The novel application of microRNA
      manipulation both in the generation of iPS cells and subsequent lineage-directed
      differentiation is discussed. Potential applications of induced pluripotent stem
      cell--a relatively new type of pluripotent stem cells--for human disease modeling
      by employing human iPS cells derived from normal and diseased somatic cells and
      iPS cells derived from mouse models of human disease may lead to uncovering of
      disease mechanisms and novel therapies.

PMID- 22619498
TI  - Prevention of chronic experimental colitis induced by dextran sulphate sodium
      (DSS) in mice treated with FR91.
AB  - One of the main treatments currently used in humans to fight cancer is
      chemotherapy. A huge number of compounds with antitumor activity are present in
      nature, and many of their derivatives are produced by microorganisms. However,
      the search for new drugs still represents a main objective for cancer therapy,
      due to drug toxicity and resistance to multiple chemotherapeutic drugs. In animal
      models, a short-time oral administration of dextran sulfate sodium (DSS) induces
      colitis, which exhibits several clinical and histological features similar to
      ulcerative colitis (UC). However, the pathogenic factors responsible for DSS
      induced colitis and the subsequent colon cancer also remain unclear. We
      investigated the effect of FR91, a standardized lysate of microbial cells
      belonging to the Bacillus genus which has been previously shown to have
      significant immunomodulatory effects, against intestinal inflammation. Colitis
      was induced in mice during 5 weeks by oral administration 2% (DSS). Morphological
      changes in the colonic mucosa were evaluated by hematoxylin-eosin staining and
      immunohistochemistry methods. Adenocarcinoma and cryptal cells of the dysplastic
      epithelium showed cathenin-beta, MLH1, APC, and p53 expression, together with
      increased production of IFN-gamma. In our model, the optimal dose response was
      the 20% FR91 concentration, where no histological alterations or mild DSS-induced
      lesions were observed. These results indicate that FR91 may act as a
      chemopreventive agent against inflammation in mice DSS-induced colitis.

PMID- 22619499
TI  - Facing current quantification challenges in protein microarrays.
AB  - The proteome is highly variable and differs from cell to cell. The reasons are
      posttranslational modifications, splice variants, and polymorphisms. Techniques
      like next-generation sequencing can only give an inadequate picture of the
      protein status of a cell. Protein microarrays are able to track these changes on
      the level they occur: the proteomic level. Therefore, protein microarrays are
      powerful tools for relative protein quantification, to unveil new interaction
      partners and to track posttranslational modifications. This papers gives an
      overview on current protein microarray techniques and discusses recent advances
      in relative protein quantification.

PMID- 22619500
TI  - What sequences on high-field MR best depict temporal resolution of experimental
      ICH and edema formation in mice?
AB  - BACKGROUND AND PURPOSE: Pilot study to examine the use of T1-, T2-, and T2*
      weighted images for evaluating hematoma size and extent of edema in mouse brain
      at high field. METHODS: Following collagenase-induced intracerebral hemorrhage,
      nine mice were imaged at 4.7 T using T1-, T2-, and T2*-weighted images for
      hematoma and edema quantitation on days 1, 3, 10, and 21 after surgery. Values
      were compared with morphometric analysis of cryosections at the time of final MR
      imaging. RESULTS: For hematoma quantitation, the Spearman correlation coefficient
      (r) between T1 signal change and histology was 0.70 (P < 0.04) compared with r =
      0.61 (P < 0.09) for T2*. The extent of perihematomal edema formation on
      cryosections was well reflected on T2 with r = 0.73 (P < 0.03). CONCLUSIONS:
      Within the limits of our pilot study, MR imaging on 4.7 T appears to approximate
      the temporal changes in hematoma and edema sizes in murine ICH well, thus laying
      the groundwork for longitudinal studies on hematoma resorption and edema
      formation.

PMID- 22619501
TI  - Identification of a gene expression signature common to distinct cancer pathways.
AB  - Mutations in cancer-causing genes induce changes in gene expression programs
      critical for malignant cell transformation. Publicly available gene expression
      profiles produced by modulating the expression of distinct cancer genes may
      therefore represent a rich resource for the identification of gene signatures
      common to seemingly unrelated cancer genes. We combined automatic retrieval with
      manual validation to obtain a data set of high-quality gene microarray profiles.
      This data set was used to create logical models of the signaling events
      underlying the observed expression changes produced by various cancer genes and
      allowed to uncover unknown and verifiable interactions. Data clustering revealed
      novel sets of gene expression profiles commonly regulated by distinct cancer
      genes. Our method allows retrieval of significant new information and testable
      hypotheses from a pool of deposited cancer gene expression experiments that are
      otherwise not apparent or appear insignificant from single measurements. The
      complete results are available through a web-application at
      http://biodata.ethz.ch/cgi-bin/geologic.

PMID- 22619502
TI  - Prognosis of treatment response (pathological complete response) in breast
      cancer.
AB  - Pertaining to the female population in the USA, breast cancer is the leading
      cancer in terms of annual incidence rate and, in terms of mortality, the second
      most lethal cancer. There are currently no biomarkers available that can predict
      which breast cancer patients will respond to chemotherapy with both sensitivity
      and specificity > 80%, as mandated by the latest FDA requirements. In this study,
      we have developed a prognostic biomarker model (complex mathematical function)
      that-based on global gene expression analysis of tumor tissue collected during
      biopsy and prior to the commencement of chemotherapy-can identify with a high
      accuracy those patients with breast cancer (clinical stages I-III) who will
      respond to the paclitaxel-fluorouracil-doxorubicin-cyclophosphamide chemotherapy
      and will experience pathological complete response (Responders), as well as those
      breast cancer patients (clinical stages I-III) who will not do so (Non
      Responders). Most importantly, both the application and the accuracy of our
      breast cancer prognostic biomarker model are independent of the status of the
      hormone receptors ER, PR, and HER2, as well as of the ethnicity and age of the
      subjects. We developed our prognostic biomarker model with 50 subjects [10
      responders (R) and 40 non-responders (NR)], and we validated it with 43 unknown
      (new and different) subjects [10 responders (R) and 33 non-responders (NR)]. All
      93 subjects were recruited at five different clinical centers around the world.
      The overall sensitivity and specificity of our prognostic biomarker model were
      90.0% and 91.8%, respectively. The nine most significant genes identified, which
      comprise the input variables to the mathematical function, are involved in
      regulation of transcription; cell proliferation, invasion, and migration;
      oncogenesis; suppression of immune response; and drug resistance and cancer
      recurrence.

PMID- 22619503
TI  - Histochemical and biochemical analysis of the size-dependent nanoimmunoresponse
      in mouse Peyer's patches using fluorescent organosilica particles.
AB  - BACKGROUND/OBJECTIVE: The size-dependent mucosal immunoresponse against
      nanomaterials (nanoimmunoresponse) is an important approach for mucosal
      vaccination. In the present work, the size-dependent nanoimmunoresponse of mouse
      Peyer's patches (PPs) and immunoglobulin A (IgA) level was investigated using
      fluorescent thiol-organosilica particles. METHODS: Various sizes of fluorescent
      thiol-organosilica particles (100, 180, 365, 745, and 925 nm in diameter) were
      administered orally. PPs were analyzed histochemically, and IgA levels in PP
      homogenates, intestinal secretions around PPs, and bile were analyzed
      biochemically. RESULTS: When compared with the larger particles (745 and 925 nm),
      oral administration of smaller thiol-organosilica particles (100, 180, and 365
      nm) increased the number of CD11b(+) macrophages and IgA(+) cells in the
      subepithelial domes of the PPs. Additionally, administration of larger particles
      induced the expression of alpha-L-fucose and mucosal IgA on the surface of M
      cells in the follicle-associated epithelia of PPs and increased the number of
      33D1(+) dendritic cells in the subepithelial domes of the PPs. IgA contents in
      the bile and PP homogenates were high after the administration of the 100 nm
      particles, but IgA levels in the intestinal secretions were high after the
      administration of the 925 nm particles. Two size-dependent routes of IgA
      secretions into the intestinal lumen, the enterohepatic route for smaller
      particles and the mucosal route for larger particles were proposed. CONCLUSION:
      Thiol-organosilica particles demonstrated size-dependent nanoimmunoresponse after
      oral administration. The size of the particles may control the mucosal immunity
      in PPs and were useful in mucosal vaccination approaches.

PMID- 22619504
TI  - Probable biofilm formation in the cheek as a complication of soft tissue filler
      resulting from improper endodontic treatment of tooth 16.
AB  - Injectable filling agents offer the promise of a better appearance without
      surgery and, among them, hyaluronic acid is the most commonly used. Although
      complications are rare, it is necessary to know the possible side effects and
      complications in order to be prepared for their management. That is why many
      researchers have been focusing on the interactions between hyaluronic acid and
      pathogens, inflammatory mediators, the immune system, and markers of oxidative
      stress to achieve efficient drug delivery, given that hyaluronic acid has
      widening applications in the field of nanomedicine. Here we report the case of a
      37-year-old female patient who returned to our clinic with an abscess in her left
      cheek 3 months after a deep injection of 1 mL of stabilized hyaluronic acid in
      both cheeks. Steroid and antibiotic therapy was initiated without success, and
      abscess drainage was performed. Extraction of tooth 16 was performed 11 days
      after insertion of drains into the abscess. Laboratory blood tests showed acute
      inflammation of presumed bacterial etiology. Microbiological examination of pus
      was negative. Bacterial cultures were found in the extracted tooth. After
      antibiotic therapy, a complete reversal of the pathological process was observed.
      The present report highlights the need to assess periodontal problems prior to
      any aesthetic facial treatment. Analyses of further case reports and clinical
      studies are necessary to understand the potential role of hyaluronic acid in the
      formation of biofilm, and how to avoid this complication, thereby increasing the
      safety of hyaluronic acid-based procedures.

PMID- 22619505
TI  - Combination of TRAIL and actinomycin D liposomes enhances antitumor effect in non
      small cell lung cancer.
AB  - The intractability of non-small cell lung cancer (NSCLC) to multimodality
      treatments plays a large part in its extremely poor prognosis. Tumor necrosis
      factor-related apoptosis-inducing ligand (TRAIL) is a promising cytokine for
      selective induction of apoptosis in cancer cells; however, many NSCLC cell lines
      are resistant to TRAIL-induced apoptosis. The therapeutic effect can be restored
      by treatments combining TRAIL with chemotherapeutic agents. Actinomycin D (ActD)
      can sensitize NSCLC cells to TRAIL-induced apoptosis by upregulation of death
      receptor 4 (DR4) or 5 (DR5). However, the use of ActD has significant drawbacks
      due to the side effects that result from its nonspecific biodistribution in vivo.
      In addition, the short half-life of TRAIL in serum also limits the antitumor
      effect of treatments combining TRAIL and ActD. In this study, we designed a
      combination treatment of long-circulating TRAIL liposomes and ActD liposomes with
      the aim of resolving these problems. The combination of TRAIL liposomes and ActD
      liposomes had a synergistic cytotoxic effect against A-549 cells. The mechanism
      behind this combination treatment includes both increased expression of DR5 and
      caspase activation. Moreover, systemic administration of the combination of TRAIL
      liposomes and ActD liposomes suppressed both tumor formation and growth of
      established subcutaneous NSCLC xenografts in nude mice, inducing apoptosis
      without causing significant general toxicity. These results provide preclinical
      proof-of-principle for a novel therapeutic strategy in which TRAIL liposomes are
      safely combined with ActD liposomes.

PMID- 22619506
TI  - The use of dopamine-hyaluronate associate-coated maghemite nanoparticles to label
      cells.
AB  - Sodium hyaluronate (HA) was associated with dopamine (DPA) and introduced as a
      coating for maghemite (gamma-Fe(2)O(3)) nanoparticles obtained by the
      coprecipitation of iron(II) and iron(III) chlorides and oxidation with sodium
      hypochlorite. The effects of the DPA anchorage of HA on the gamma-Fe(2)O(3)
      surface on the physicochemical properties of the resulting colloids were
      investigated. Nanoparticles coated at three different DPA-HA/gamma-Fe(2)O(3) and
      DPA/HA ratios were chosen for experiments with rat bone marrow mesenchymal stem
      cells and human chondrocytes. The nanoparticles were internalized into rat bone
      marrow mesenchymal stem cells via endocytosis as confirmed by Prussian Blue
      staining. The efficiency of mesenchymal stem cell labeling was analyzed. From
      among the investigated samples, efficient cell labeling was achieved by using DPA
      HA-gamma-Fe(2)O(3) nanoparticles with DPA-HA/gamma-Fe(2)O(3) = 0.45 (weight/
      weight) and DPA/HA = 0.038 (weight/weight) ratios. The particles were used as a
      contrast agent in magnetic resonance imaging for the labeling and visualization
      of cells.

PMID- 22619507
TI  - PLGA nanoparticle-mediated delivery of tumor antigenic peptides elicits effective
      immune responses.
AB  - The peptide vaccine clinical trials encountered limited success because of
      difficulties associated with stability and delivery, resulting in inefficient
      antigen presentation and low response rates in patients with cancer. The purpose
      of this study was to develop a novel delivery approach for tumor antigenic
      peptides in order to elicit enhanced immune responses using poly(DL-lactide-co
      glycolide) nanoparticles (PLGA-NPs) encapsulating tumor antigenic peptides. PLGA
      NPs were made using the double emulsion-solvent evaporation method. Artificial
      antigen-presenting cells were generated by human dendritic cells (DCs) loaded
      with PLGA-NPs encapsulating tumor antigenic peptide(s). The efficiency of the
      antigen presentation was measured by interferon-gamma ELISpot assay (Vector
      Laboratories, Burlingame, CA). Antigen-specific cytotoxic T lymphocytes (CTLs)
      were generated and evaluated by CytoTox 96((r)) Non-Radioactive Cytotoxicity
      Assay (Promega, Fitchburg, WI). The efficiency of the peptide delivery was
      compared between the methods of emulsification in incomplete Freund's adjuvant
      and encapsulation in PLGA-NPs. Our results showed that most of the PLGA-NPs were
      from 150 nm to 500 nm in diameter, and were negatively charged at pH 7.4 with a
      mean zeta potential of -15.53 +/- 0.71 mV; the PLGA-NPs could be colocalized in
      human DCs in 30 minutes of incubation. Human DCs loaded with PLGA-NPs
      encapsulating peptide induced significantly stronger CTL cytotoxicity than those
      pulsed with free peptide, while human DCs loaded with PLGA-NPs encapsulating a
      three-peptide cocktail induced a significantly greater CTL response than those
      encapsulating a two-peptide cocktail. Most importantly, the peptide dose
      encapsulated in PLGA-NPs was 63 times less than that emulsified in incomplete
      Freund's adjuvant, but it induced a more powerful CTL response in vivo. These
      results demonstrate that the delivery of peptides encapsulated in PLGA-NPs is a
      promising approach to induce effective antitumor CTL responses in vivo.

PMID- 22619508
TI  - Selective targeting of melanoma by PEG-masked protein-based multifunctional
      nanoparticles.
AB  - BACKGROUND: Nanoparticle-based systems are promising for the development of
      imaging and therapeutic agents. The main advantage of nanoparticles over
      traditional systems lies in the possibility of loading multiple functionalities
      onto a single molecule, which are useful for therapeutic and/or diagnostic
      purposes. These functionalities include targeting moieties which are able to
      recognize receptors overexpressed by specific cells and tissues. However,
      targeted delivery of nanoparticles requires an accurate system design. We present
      here a rationally designed, genetically engineered, and chemically modified
      protein-based nanoplatform for cell/tissue-specific targeting. METHODS: Our
      nanoparticle constructs were based on the heavy chain of the human protein
      ferritin (HFt), a highly symmetrical assembly of 24 subunits enclosing a hollow
      cavity. HFt-based nanoparticles were produced using both genetic engineering and
      chemical functionalization methods to impart several functionalities, ie, the
      alpha-melanocyte-stimulating hormone peptide as a melanoma-targeting moiety,
      stabilizing and HFt-masking polyethylene glycol molecules, rhodamine
      fluorophores, and magnetic resonance imaging agents. The constructs produced were
      extensively characterized by a number of physicochemical techniques, and assayed
      for selective melanoma-targeting in vitro and in vivo. RESULTS: Our HFt-based
      nanoparticle constructs functionalized with the alpha-melanocyte-stimulating
      hormone peptide moiety and polyethylene glycol molecules were specifically taken
      up by melanoma cells but not by other cancer cell types in vitro. Moreover,
      experiments in melanoma-bearing mice indicate that these constructs have an
      excellent tumor-targeting profile and a long circulation time in vivo.
      CONCLUSION: By masking human HFt with polyethylene glycol and targeting it with
      an alpha-melanocyte-stimulating hormone peptide, we developed an HFt-based
      melanoma-targeting nanoplatform for application in melanoma diagnosis and
      treatment. These results could be of general interest, because the same strategy
      can be exploited to develop ad hoc nanoplatforms for specific delivery towards
      any cell/tissue type for which a suitable targeting moiety is available.

PMID- 22619509
TI  - Induction of cell death in a glioblastoma line by hyperthermic therapy based on
      gold nanorods.
AB  - BACKGROUND: Metallic nanorods are promising agents for a wide range of biomedical
      applications. In this study, we developed an optical hyperthermia method capable
      of inducing in vitro death of glioblastoma cells. METHODS: The procedure used was
      based on irradiation of gold nanorods with a continuous wave laser. This kind of
      nanoparticle converts absorbed light into localized heat within a short period of
      time due to the surface plasmon resonance effect. The effectiveness of the method
      was determined by measuring changes in cell viability after laser irradiation of
      glioblastoma cells in the presence of gold nanorods. RESULTS: Laser irradiation
      in the presence of gold nanorods induced a significant decrease in cell
      viability, while no decrease in cell viability was observed with laser
      irradiation or incubation with gold nanorods alone. The mechanism of cell death
      mediated by gold nanorods during photothermal ablation was analyzed, indicating
      that treatment compromised the integrity of the cell membrane instead of
      initiating the process of programmed cell death. CONCLUSION: The use of gold
      nanorods in hyperthermal therapies is very effective in eliminating glioblastoma
      cells, and therefore represents an important area of research for therapeutic
      development.

PMID- 22619511
TI  - Controlled synthesis and characterization of hollow flower-like silver
      nanostructures.
AB  - BACKGROUND: The synthesis of anisotropic silver nanoparticles is a time-consuming
      process and involves the use of expensive toxic chemicals and specialized
      laboratory equipment. The presence of toxic chemicals in the prepared anisotropic
      silver nanostructures hindered their medical application. The authors have
      developed a fast and inexpensive method for the synthesis of three-dimensional
      hollow flower-like silver nanostructures without the use of toxic chemicals.
      METHODS: In this method, silver nitrate was reduced using dextrose in presence of
      trisodium citrate as a capping agent. Sodium hydroxide was added to enhance
      reduction efficacy of dextrose and reduce time of synthesis. The effects of all
      four agents on the shape and size of silver nanostructures were investigated.
      RESULTS: Robust hollow flower-like silver nanostructures were successfully
      synthesized and ranged in size from 0.2 MUm to 5.0 MUm with surface area between
      25-240 m(2)/g. Changing the concentration of silver nitrate, dextrose, sodium
      hydroxide, and trisodium citrate affected the size and shape of the synthesized
      structures, while changing temperature had no effect. CONCLUSION: The proposed
      method is simple, safe, and allows controlled synthesis of anisotropic silver
      nanostructures, which may represent promising tools as effective antimicrobial
      agents and for in vitro diagnostics. The synthesized hollow nanostructures may be
      used for enhanced drug encapsulation and sustained release.

PMID- 22619510
TI  - Exosome mimetics: a novel class of drug delivery systems.
AB  - The identification of extracellular phospholipid vesicles as conveyors of
      cellular information has created excitement in the field of drug delivery.
      Biological therapeutics, including short interfering RNA and recombinant
      proteins, are prone to degradation, have limited ability to cross biological
      membranes, and may elicit immune responses. Therefore, delivery systems for such
      drugs are under intensive investigation. Exploiting extracellular vesicles as
      carriers for biological therapeutics is a promising strategy to overcome these
      issues and to achieve efficient delivery to the cytosol of target cells. Exosomes
      are a well studied class of extracellular vesicles known to carry proteins and
      nucleic acids, making them especially suitable for such strategies. However, the
      considerable complexity and the related high chance of off-target effects of
      these carriers are major barriers for translation to the clinic. Given that it is
      well possible that not all components of exosomes are required for their proper
      functioning, an alternative strategy would be to mimic these vesicles
      synthetically. By assembly of liposomes harboring only crucial components of
      natural exosomes, functional exosome mimetics may be created. The low complexity
      and use of well characterized components strongly increase the pharmaceutical
      acceptability of such systems. However, exosomal components that would be
      required for the assembly of functional exosome mimetics remain to be identified.
      This review provides insights into the composition and functional properties of
      exosomes, and focuses on components which could be used to enhance the drug
      delivery properties of exosome mimetics.

PMID- 22619514
TI  - A novel polyethyleneimine-coated adeno-associated virus-like particle formulation
      for efficient siRNA delivery in breast cancer therapy: preparation and in vitro
      analysis.
AB  - BACKGROUND: Systemic delivery of small interfering RNA (siRNA) is limited by its
      poor stability and limited cell-penetrating properties. To overcome these
      limitations, we designed an efficient siRNA delivery system using
      polyethyleneimine-coated virus-like particles derived from adeno-associated virus
      type 2 (PEI-AAV2-VLPs). METHODS: AAV2-VLPs were produced in insect cells by
      infection with a baculovirus vector containing three AAV2 capsid genes. Using
      this method, we generated well dispersed AAV2-VLPs with an average diameter of 20
      nm, similar to that of the wild-type AAV2 capsid. The nanoparticles were
      subsequently purified by chromatography and three viral capsid proteins were
      confirmed by Western blot. The negatively charged AAV2-VLPs were surface-coated
      with PEI to develop cationic nanoparticles, and the formulation was used for
      efficient siRNA delivery under optimized transfection conditions. RESULTS: PEI
      AAV2-VLPs were able to condense siRNA and to protect it from degradation by
      nucleases, as confirmed by gel electrophoresis. siRNA delivery mediated by PEI
      AAV2-VLPs resulted in a high transfection rate in MCF-7 breast cancer cells with
      no significant cytotoxicity. A cell death assay also confirmed the efficacy and
      functionality of this novel siRNA formulation towards MCF-7 cancer cells, in
      which more than 60% of cell death was induced within 72 hours of transfection.
      CONCLUSION: The present study explores the potential of virus-like particles as a
      new approach for gene delivery and confirms its potential for breast cancer
      therapy.

PMID- 22619515
TI  - Theranostic liposomes loaded with quantum dots and apomorphine for brain
      targeting and bioimaging.
AB  - Quantum dots (QDs) and apomorphine were incorporated into liposomes to eliminate
      uptake by the liver and enhance brain targeting. We describe the preparation,
      physicochemical characterization, in vivo bioimaging, and brain endothelial cell
      uptake of the theranostic liposomes. QDs and the drug were mainly located in the
      bilayer membrane and inner core of the liposomes, respectively. Spherical
      vesicles with a mean diameter of ~140 nm were formed. QDs were completely
      encapsulated by the vesicles. Nearly 80% encapsulation percentage was achieved
      for apomorphine. A greater fluorescence intensity was observed in mouse brains
      treated with liposomes compared to free QDs. This result was further confirmed by
      ex vivo imaging of the organs. QD uptake by the heart and liver was reduced by
      liposomal incorporation. Apomorphine accumulation in the brain increased by 2.4
      fold after this incorporation. According to a hyperspectral imaging analysis,
      multifunctional liposomes but not the aqueous solution carried QDs into the
      brain. Liposomes were observed to have been efficiently endocytosed into bEND3
      cells. The mechanisms involved in the cellular uptake were clathrin- and caveola
      mediated endocytosis, which were energy-dependent. To the best of our knowledge,
      our group is the first to develop liposomes with a QD-drug hybrid for the aim of
      imaging and treating brain disorders.

PMID- 22619512
TI  - Inhaled chemotherapy in lung cancer: future concept of nanomedicine.
AB  - Regional chemotherapy was first used for lung cancer 30 years ago. Since then,
      new methods of drug delivery and pharmaceuticals have been investigated in vitro,
      and in animals and humans. An extensive review of drug delivery systems,
      pharmaceuticals, patient monitoring, methods of enhancing inhaled drug
      deposition, safety and efficacy, and also additional applications of inhaled
      chemotherapy and its advantages and disadvantages are presented. Regional
      chemotherapy to the lung parenchyma for lung cancer is feasible and efficient.
      Safety depends on the chemotherapy agent delivered to the lungs and is dose
      dependent and time-dependent. Further evaluation is needed to provide data
      regarding early lung cancer stages, and whether regional chemotherapy can be used
      as neoadjuvant or adjuvant treatment. Finally, inhaled chemotherapy could one day
      be administered at home with fewer systemic adverse effects.

PMID- 22619516
TI  - Enhancing cellular uptake of activable cell-penetrating peptide-doxorubicin
      conjugate by enzymatic cleavage.
AB  - The use of activable cell-penetrating peptides (ACPPs) as molecular imaging
      probes is a promising new approach for the visualization of enzymes. The cell
      penetrating function of a polycationic cell-penetrating peptide (CPP) is
      efficiently blocked by intramolecular electrostatic interactions with a
      polyanionic peptide. Proteolysis of a proteinase-sensitive substrate present
      between the CPP and polyanionic peptide affords dissociation of both domains and
      enables the activated CPP to enter cells. This ACPP strategy could also be used
      to modify antitumor agents for tumor-targeting therapy. Here, we aimed to develop
      a conjugate of ACPP with antitumor drug doxorubicin (DOX) sensitive to matrix
      metalloproteinase-2 and -9 (MMP-2/9) for tumor-targeting therapy purposes. The
      ACPP-DOX conjugate was successfully synthesized. Enzymatic cleavage of ACPP-DOX
      conjugate by matrix metalloproteinase (MMP)-2/9 indicated that the activation of
      ACPP-DOX occurred in an enzyme concentration-dependent manner. Flow cytometry and
      laser confocal microscope studies revealed that the cellular uptake of ACPP-DOX
      was enhanced after enzymatic-triggered activation and was higher in HT-1080 cells
      (overexpressed MMPs) than in MCF-7 cells (under-expressed MMPs). The
      antiproliferative assay showed that ACPP had little toxicity and that ACPP-DOX
      effectively inhibited HT-1080 cell proliferation. These experiments revealed that
      the ACPP-DOX conjugate could be triggered by MMP-2/9, which enabled the activated
      CPP-DOX to enter cells. ACPP-DOX conjugate may be a potential prodrug delivery
      system used to carry antitumor drugs for MMP-related tumor therapy.

PMID- 22619517
TI  - A nanohybrid system for taste masking of sildenafil.
AB  - A nanohybrid was prepared with an inorganic clay material, montmorillonite (MMT),
      for taste masking of sildenafil (SDN). To further improve the taste-masking
      efficiency and enhance the drug-release rate, we coated the nanohybrid of SDN-MMT
      with a basic polymer, polyvinylacetal diethylaminoacetate (AEA). Powder X-ray
      diffraction and Fourier transform infrared experiments showed that SDN was
      successfully intercalated into the interlayer space of MMT. The AEA-coated SDN
      MMT nanohybrid showed drug release was much suppressed at neutral pH (release
      rate, 4.70 +/- 0.53%), suggesting a potential for drug taste masking at the
      buccal cavity. We also performed in vitro drug release experiments in a simulated
      gastric fluid (pH = 1.2) and compared the drug-release profiles of AEA-coated SDN
      MMT and Viagra((r)), an approved dosage form of SDN. As a result, about 90% of
      SDN was released from the AEA-coated SDN-MMT during the first 2 hours while
      almost 100% of drug was released from Viagra((r)). However, an in vivo experiment
      showed that the AEA-coated SDN-MMT exhibited higher drug exposure than
      Viagra((r)). For the AEA-coated SDN-MMT, the area under the plasma concentration-
      time curve from 0 hours to infinity (AUC(0-infinity)) and maximum concentration
      (C(max)) were 78.8 +/- 2.32 MUg . hour/mL and 12.4 +/- 0.673 MUg/mL,
      respectively, both of which were larger than those obtained with Viagra((r))
      (AUC(0-infinity) = 69.2 +/- 3.19 MUg . hour/mL; C(max) = 10.5 +/- 0.641 MUg/mL).
      Therefore, we concluded that the MMT-based nanohybrid is a promising delivery
      system for taste masking of SDN with possibly improved drug exposure.

PMID- 22619518
TI  - Gold nanoparticles and diclofenac diethylammonium administered by iontophoresis
      reduce inflammatory cytokines expression in Achilles tendinitis.
AB  - INTRODUCTION: Tendinitis affects a substantial number of people in several
      occupations involving repetitive work or direct trauma. Iontophoresis is a
      therapeutic alternative used in the treatment of injury during the inflammatory
      phase. In recent years, gold nanoparticles (GNP) have been studied due to their
      therapeutic anti-inflammatory capacity and as an alternative to the transport of
      several proteins. PURPOSE: This study evaluates the therapeutic effects of
      iontophoresis using GNPs and diclofenac diethylammonium on inflammatory
      parameters in rats challenged with traumatic tendinitis. METHODS: Wistar rats
      were divided in three treatment groups (n = 15): (1) iontophoresis + diclofenac
      diethylammonium; (2) iontophoresis + GNP; and (3) iontophoresis + diclofenac
      diethylammonium + GNP. External control was formed by challenged tendons without
      treatment (n = 15). Iontophoresis was administered using 0.3 mA direct current on
      1.5 cm(2) electrodes. RESULTS: The levels of both inflammatory cytokines were
      significantly higher in untreated challenged rats, when compared with the control
      (5.398 +/- 234 for interleukin 1 beta and 6.411 +/- 432 for tumor necrosis factor
      alpha), which confirms the occurrence of an inflammatory stage in injury (P <
      0.05). A significant decrease was observed in expression of cytokines interleukin
      1 beta in the three treatment groups, in comparison with untreated challenged
      tendons, although, in the group treated with diclofenac and GNP, results were
      similar to the control (1.732 +/- 239) (P < 0.05). Concerning tumor necrosis
      factor alpha, only the group treated with the association diclofenac and GNPs
      presented decreased levels, compared with the control (3.221 +/- 369) (P < 0.05).
      CONCLUSION: The results show the efficacy of drug administration using direct
      current to treat tendinitis in an animal model, and the potential anti
      inflammatory, carrier, and enhancing effects of GNPs in iontophoresis.

PMID- 22619519
TI  - Passive targeting of ischemic-reperfused myocardium with adenosine-loaded silica
      nanoparticles.
AB  - Pharmacological agents suggested for infarct size limitation have serious side
      effects when used at cardioprotective doses which hinders their translation into
      clinical practice. The solution to the problem might be direct delivery of
      cardioprotective drugs into ischemic-reperfused myocardium. In this study, we
      explored the potential of silica nanoparticles for passive delivery of adenosine,
      a prototype cardioprotective agent, into ischemic-reperfused heart tissue. In
      addition, the biodegradation of silica nanoparticles was studied both in vitro
      and in vivo. Immobilization of adenosine on the surface of silica nanoparticles
      resulted in enhancement of adenosine-mediated infarct size limitation in the rat
      model. Furthermore, the hypotensive effect of adenosine was attenuated after its
      adsorption on silica nanoparticles. We conclude that silica nanoparticles are
      biocompatible materials that might potentially be used as carriers for heart
      targeted drug delivery.

PMID- 22619520
TI  - Co-encapsulation of magnetic Fe3O4 nanoparticles and doxorubicin into
      biodegradable PLGA nanocarriers for intratumoral drug delivery.
AB  - In this study, the authors constructed a novel PLGA [poly(D,L-lactic-co-glycolic
      acid)]-based polymeric nanocarrier co-encapsulated with doxorubicin (DOX) and
      magnetic Fe(3)O(4) nanoparticles (MNPs) using a single emulsion evaporation
      method. The DOX-MNPs showed high entrapment efficiency, and they supported a
      sustained and steady release of DOX. Moreover, the drug release was pH sensitive,
      with a faster release rate in an acidic environment than in a neutral
      environment. In vitro, the DOX-MNPs were easily internalized into murine Lewis
      lung carcinoma cells and they induced apoptosis. In vivo, the DOX-MNPs showed
      higher antitumor activity than free DOX solution. Furthermore, the antitumor
      activity of the DOX-MNPs was higher with than without an external magnetic field;
      they were also associated with smaller tumor volume and a lower metastases
      incidence rate. This work may provide a new modality for developing an effective
      drug delivery system.

PMID- 22619523
TI  - Pharmacokinetics, tissue distribution, and metabolites of a polyvinylpyrrolidone
      coated norcantharidin chitosan nanoparticle formulation in rats and mice, using
      LC-MS/MS.
AB  - A novel formulation containing polyvinylpyrrolidone (PVP) K(30)-coated
      norcantharidin (NCTD) chitosan nanoparticles (PVP-NCTD-NPs) was prepared by ionic
      gelation between chitosan and sodium tripolyphosphate. The average particle size
      of the PVP-NCTD-NPs produced was 140.03 +/- 6.23 nm; entrapment efficiency was
      56.33% +/- 1.41%; and drug-loading efficiency was 8.38% +/- 0.56%. The surface
      morphology of NCTD nanoparticles (NPs) coated with PVP K(30) was characterized
      using various analytical techniques, including X-ray diffraction and atomic force
      microscopy. NCTD and its metabolites were analyzed using a sensitive and specific
      liquid chromatography-tandem mass spectrometry method with samples from mice and
      rats. The results indicated the importance of the PVP coating in controlling the
      shape and improving the entrapment efficiency of the NPs. Pharmacokinetic
      profiles of the NCTD group and PVP-NCTD-NP group, after oral and intravenous
      administration in rats, revealed that relative bioavailabilities were 173.3% and
      325.5%, respectively. The elimination half-life increased, and there was an
      obvious decrease in clearance. The tissue distribution of NCTD in mice after the
      intravenous administration of both formulations was investigated. The drug was
      not quantifiable at 6 hours in all tissues except for the liver and kidneys. The
      distribution of the drug in the liver and bile was notably improved in the PVP
      NCTD-NP group. The metabolites and excretion properties of NCTD were investigated
      by analyzing rat feces and urine samples, collected after oral administration. A
      prototype drug and two metabolites were found in the feces, and seven metabolites
      in the urine. The primary elimination route of NCTD was via the urine. The
      quantity of the parent drug eliminated in the feces of the PVP-NCTD-NP group, was
      32 times greater than that of the NCTD group, indicating that the NPs
      dramatically increased the reduction quantity from liver to bile. We conclude
      that PVP-NCTD-NPs are an adequate formulation for enhancing the absorption of
      NCTD, and significantly improving therapeutic effects targeting the hepatic
      system. Decarboxylation and hydroxylation were the dominant metabolic pathways
      for NCTD. Metabolites were mainly excreted into rat kidney and finally into
      urine.

PMID- 22619522
TI  - Encapsulated nanoepigallocatechin-3-gallate and elemental selenium nanoparticles
      as paradigms for nanochemoprevention.
AB  - Chemoprevention that impedes one or more steps in carcinogenesis, via long-term
      administration of naturally occurring or synthetic compounds, is widely
      considered to be a crucial strategy for cancer control. Selenium (Se) has
      chemopreventive effects, but its application is limited due to a low therapeutic
      index as shown in numerous animal experiments. In contrast to Se, which was known
      for its toxicity prior to the discovery of its beneficial effects, the natural
      compound epigallocatechin-3-gallate (EGCG) was originally considered to be
      nontoxic. Due to its preventive effects on many types of cancer in various animal
      models, EGCG has been regarded as a prime example of a promising chemopreventive
      agent without major toxicity concerns. However, very recently, evidence has
      accumulated showing that efficacious doses of EGCG used in health promotion may
      not be far from its toxic dose level. Therefore, both Se and EGCG need to be
      modified by novel pharmaceutical technologies to attain enhanced efficacy and/or
      reduced toxicity. Nanotechnology may be one of these technologies. In support of
      this hypothesis, the characteristics of polylactic acid and polyethylene glycol
      encapsulated nano-EGCG and elemental Se nanoparticles dispersed by bovine serum
      albumin are reviewed in this article. Encapsulation of EGCG to form nano-EGCG
      leads to its enhanced stability in plasma and remarkably superior chemopreventive
      effects, with more than tenfold dose advantages in inducing apoptosis and
      inhibition of both angiogenesis and tumor growth. Se at nanoparticle size ("Nano
      Se"), compared with Se compounds commonly used in dietary supplements, has
      significantly lower toxicity, without compromising its ability to upregulate
      selenoenzymes at nutritional levels and induce phase II enzymes at
      supranutritional levels.

PMID- 22619524
TI  - Improving thermal stability and efficacy of BCNU in treating glioma cells using
      PAA-functionalized graphene oxide.
AB  - BACKGROUND: 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), a commercial
      chemotherapeutic drug for treating malignant brain tumors, has poor thermal
      stability and a short half-life. Immobilization of BCNU on a nanocarrier might
      increase the thermal stability of BCNU and extend its half-life. METHODS:
      Nanosized graphene oxide (GO) could be modified by polyacrylic acid (PAA) to
      improve the aqueous solubility and increase the cell penetration efficacy of the
      nanocarrier. PAA-GO intended as a drug carrier for BCNU was prepared and
      characterized in this study. The size and thickness of PAA-GO was investigated by
      transmission electron microscopy and atomic force microscopy, and the presence of
      PAA functional groups was confirmed by electron spectroscopy for chemical
      analysis and thermogravimetric analysis. BCNU was conjugated to PAA-GO by
      covalent binding for specific killing of cancer cells, which could also enhance
      the thermal stability of the drug. RESULTS: Single layer PAA-GO (about 1.9 nm)
      with a lateral width as small as 36 nm was successfully prepared. The optimum
      drug immobilization condition was by reacting 0.5 mg PAA-GO with 0.4 mg BCNU, and
      the drug-loading capacity and residual drug activity were 198 MUg BCNU/mg PAA-GO
      and 70%, respectively. This nanocarrier significantly prolonged the half-life of
      bound BCNU from 19 to 43 hours compared with free drug and showed efficient
      intracellular uptake by GL261 cancer cells. The in vitro anticancer efficacy of
      PAA-GO-BCNU was demonstrated by a 30% increase in DNA interstrand cross-linking
      and a 77% decrease in the IC(50) value toward GL261 compared with the same dosage
      of free drug. CONCLUSION: Nanosized PAA-GO serves as an efficient BCNU
      nanocarrier by covalent binding. This nanocarrier will be a promising new vehicle
      for an advanced drug delivery system in cancer therapy.

PMID- 22619525
TI  - Self-assembled mPEG-PCL-g-PEI micelles for simultaneous codelivery of
      chemotherapeutic drugs and DNA: synthesis and characterization in vitro.
AB  - BACKGROUND: In this paper, a series of amphiphilic triblock copolymers based on
      polyethylene glycol-poly E-caprolactone-polyethylenimine (mPEG-PCL-g-PEI) were
      successfully synthesized, and their application for codelivery of
      chemotherapeutic drugs and DNA simultaneously was investigated. METHODS AND
      RESULTS: These copolymers could self-assemble into micelles with positive
      charges. The size and zeta potential of the micelles was measured, and the
      results indicate that temperature had a large effect on the micelles obtained. In
      vitro gene transfection evaluation in cancer cells indicated that the self
      assembled micelles could serve as potential gene delivery vectors. In addition,
      hydrophobic drug entrapment efficiency and codelivery with the gene was also
      studied in vitro. The self-assembled micelles could load doxorubicin efficiently
      and increase cellular uptake in vitro, while maintaining high gene transfection
      efficiency. CONCLUSION: The triblock copolymer mPEG-PCL-g-PEI could be a novel
      vector for codelivery of drug and gene therapy.

PMID- 22619526
TI  - Curcumin-loaded magnetic nanoparticles for breast cancer therapeutics and imaging
      applications.
AB  - BACKGROUND: The next generation magnetic nanoparticles (MNPs) with theranostic
      applications have attracted significant attention and will greatly improve
      nanomedicine in cancer therapeutics. Such novel MNP formulations must have ultra
      low particle size, high inherent magnetic properties, effective imaging, drug
      targeting, and drug delivery properties. To achieve these characteristic
      properties, a curcumin-loaded MNP (MNP-CUR) formulation was developed. METHODS:
      MNPs were prepared by chemical precipitation method and loaded with curcumin
      (CUR) using diffusion method. The physicochemical properties of MNP-CUR were
      characterized using dynamic light scattering, transmission electron microscopy,
      and spectroscopy. The internalization of MNP-CUR was achieved after 6 hours
      incubation with MDA-MB-231 breast cancer cells. The anticancer potential was
      evaluated by a tetrazolium-based dye and colony formation assays. Further, to
      prove MNP-CUR results in superior therapeutic effects over CUR, the mitochondrial
      membrane potential integrity and reactive oxygen species generation were
      determined. Magnetic resonance imaging capability and magnetic targeting property
      were also evaluated. RESULTS: MNP-CUR exhibited individual particle grain size of
      ~9 nm and hydrodynamic average aggregative particle size of ~123 nm. Internalized
      MNP-CUR showed a preferential uptake in MDA-MB-231 cells in a concentration
      dependent manner and demonstrated accumulation throughout the cell, which
      indicates that particles are not attached on the cell surface but internalized
      through endocytosis. MNP-CUR displayed strong anticancer properties compared to
      free CUR. MNP-CUR also amplified loss of potential integrity and generation of
      reactive oxygen species upon treatment compared to free CUR. Furthermore, MNP-CUR
      exhibited superior magnetic resonance imaging characteristics and significantly
      increased the targeting capability of CUR. CONCLUSION: MNP-CUR exhibits potent
      anticancer activity along with imaging and magnetic targeting capabilities. This
      approach can be extended to preclinical and clinical use and may have importance
      in cancer treatment and cancer imaging in the future. Further, if these
      nanoparticles can functionalize with antibody/ligands, they will serve as novel
      platforms for multiple biomedical applications.

PMID- 22619527
TI  - Hierarchically nanostructured hydroxyapatite: hydrothermal synthesis, morphology
      control, growth mechanism, and biological activity.
AB  - Hierarchically nanosized hydroxyapatite (HA) with flower-like structure assembled
      from nanosheets consisting of nanorod building blocks was successfully
      synthesized by using CaCl(2), NaH(2)PO(4), and potassium sodium tartrate via a
      hydrothermal method at 200 degrees C for 24 hours. The effects of heating time
      and heating temperature on the products were investigated. As a chelating ligand
      and template molecule, the potassium sodium tartrate plays a key role in the
      formation of hierarchically nanostructured HA. On the basis of experimental
      results, a possible mechanism based on soft-template and self-assembly was
      proposed for the formation and growth of the hierarchically nanostructured HA.
      Cytotoxicity experiments indicated that the hierarchically nanostructured HA had
      good biocompatibility. It was shown by in-vitro experiments that mesenchymal stem
      cells could attach to the hierarchically nanostructured HA after being cultured
      for 48 hours. OBJECTIVE: The purpose of this study was to develop facile and
      effective methods for the synthesis of novel hydroxyapatite (HA) with
      hierarchical nanostructures assembled from independent and discrete nanobuilding
      blocks. METHODS: A simple hydrothermal approach was applied to synthesize HA by
      using CaCl(2), NaH(2)PO(4), and potassium sodium tartrate at 200 degrees C for 24
      hours. The cell cytotoxicity of the hierarchically nanostructured HA was tested
      by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay.
      RESULTS: HA displayed the flower-like structure assembled from nanosheets
      consisting of nanorod building blocks. The potassium sodium tartrate was used as
      a chelating ligand, inducing the formation and self-assembly of HA nanorods. The
      heating time and heating temperature influenced the aggregation and morphology of
      HA. The cell viability did not decrease with the increasing concentration of
      hierarchically nanostructured HA added. CONCLUSION: A novel, simple and reliable
      hydrothermal route had been developed for the synthesis of hierarchically
      nanosized HA with flower-like structure assembled from nanosheets consisting of
      nanorod building blocks. The HA with the hierarchical nanostructure was formed
      via a soft-template assisted self-assembly mechanism. The hierarchically
      nanostructured HA has a good biocompatibility and essentially no in-vitro
      cytotoxicity.

PMID- 22619528
TI  - Oridonin nanosuspension was more effective than free oridonin on G2/M cell cycle
      arrest and apoptosis in the human pancreatic cancer PANC-1 cell line.
AB  - Oridonin, a diterpenoid isolated from Rabdosia rubescencs, has been reported to
      have antitumor effects. However, low solubility has limited its clinical
      applications. Preparation of drugs in the form of nanosuspensions is an
      extensively utilized protocol. In this study, we investigated the anticancer
      activity of oridonin and oridonin nanosuspension on human pancreatic carcinoma
      PANC-1 cells. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay
      was performed to investigate the effect of oridonin on cell growth. Propidium
      iodide and Hoechst 33342 staining were used to detect morphologic changes. The
      percentage of apoptosis and cell cycle progression was determined by flow
      cytometric method staining with propidium iodide. Annexin V-fluorescein
      isothiocyanate (FITC)/PI staining was used to evaluate cell apoptosis by flow
      cytometry. Caspase-3 activity was measured by spectrophotometry. The apoptotic
      and cell cycle protein expression were determined by Western blot analysis. Both
      oridonin and oridonin nanosuspension induced apoptosis and G(2)/M phase cell
      cycle arrest, and the latter had a more significant cytotoxic effect. The ratio
      of Bcl-2/Bax protein expression was decreased and caspase- 3 activity was
      stimulated. The expression of cyclin B1 and p-cdc2 (T161) was suppressed. Our
      results showed that oridonin nanosuspension was more effective than free oridonin
      on G(2)/M cell cycle arrest and apoptosis in the human pancreatic cancer PANC-1
      cell line.

PMID- 22619529
TI  - Toxicity and antibacterial assessment of chitosan-coated silver nanoparticles on
      human pathogens and macrophage cells.
AB  - BACKGROUND: Pathogenic bacteria are able to develop various strategies to
      counteract the bactericidal action of antibiotics. Silver nanoparticles (AgNPs)
      have emerged as a potential alternative to conventional antibiotics because of
      their potent antimicrobial properties. The purpose of this study was to
      synthesize chitosan-stabilized AgNPs (CS-AgNPs) and test for their cytotoxic,
      genotoxic, macrophage cell uptake, antibacterial, and antibiofilm activities.
      METHODS: AgNPs were synthesized using chitosan as both a stabilizing and a
      reducing agent. Antibacterial activity was determined by colony-forming unit
      assay and scanning electron microscopy. Genotoxic and cytotoxic activity were
      determined by DNA fragmentation, comet, and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide] assays. Cellular uptake and intracellular
      antibacterial activity were tested on macrophages. RESULTS: CS-AgNPs exhibited
      potent antibacterial activity against different human pathogens and also impeded
      bacterial biofilm formation. Scanning electron microscopy analysis indicated that
      CS-AgNPs kill bacteria by disrupting the cell membrane. CS-AgNPs showed no
      significant cytotoxic or DNA damage effect on macrophages at the bactericidal
      dose. Propidium iodide staining indicated active endocytosis of CS-AgNPs
      resulting in reduced intracellular bacterial survival in macrophages. CONCLUSION:
      The present study concludes that at a specific dose, chitosan-based AgNPs kill
      bacteria without harming the host cells, thus representing a potential template
      for the design of antibacterial agents to decrease bacterial colonization and to
      overcome the problem of drug resistance.

PMID- 22619530
TI  - Novel norcantharidin-loaded liver targeting chitosan nanoparticles to enhance
      intestinal absorption.
AB  - In this paper, two novel liver-targeting nanoparticles, norcantharidin-loaded
      chitosan nanoparticles (NCTD-CS-NPs) and norcantharidin-associated galactosylated
      chitosan nanoparticles (NCTD-GC-NPs), were prepared using ionic cross-linkage.
      The physical properties, particle size, encapsulation efficiency, and drug
      release characteristics of the nanoparticles were investigated in vitro. To
      investigate the intestinal absorption mechanisms of the two preparations, a
      series of experiments was carried out, including in situ circulation method, in
      vitro everted gut sacs, and Ussing chamber perfusion technique. The absorption
      rate constants (Ka) of NCTD at different segments were found to be duodenum >
      jejunum > ileum > colon. The concentration had no distinctive effect on
      absorption kinetics, suggesting that drug absorption is not dose-dependent. The
      transport of NCTD was found to be inhibited by P-glycoprotein (P-gp) inhibitor,
      indicating that NCTD might be the substrate of P-gp. The order of the absorption
      enhancer effects were as follows: low molecular weight chitosan (CS-8kDa) > high
      molecular weight chitosan (CS-30kDa) > Poloxamer > sodium dodecyl sulfate (SDS) >
      sodium deoxycholate (SDCh). The results indicate that the chitosan nanoparticles
      can improve intestinal absorption of NCTD.

PMID- 22619531
TI  - RGDS-functionalized polyethylene glycol hydrogel-coated magnetic iron oxide
      nanoparticles enhance specific intracellular uptake by HeLa cells.
AB  - The objective of this study was to develop thin, biocompatible, and biofunctional
      hydrogel-coated small-sized nanoparticles that exhibit favorable stability,
      viability, and specific cellular uptake. This article reports the coating of
      magnetic iron oxide nanoparticles (MIONPs) with covalently cross-linked
      biofunctional polyethylene glycol (PEG) hydrogel. Silanized MIONPs were
      derivatized with eosin Y, and the covalently cross-linked biofunctional PEG
      hydrogel coating was achieved via surface-initiated photopolymerization of PEG
      diacrylate in aqueous solution. The thickness of the PEG hydrogel coating,
      between 23 and 126 nm, was tuned with laser exposure time. PEG hydrogel-coated
      MIONPs were further functionalized with the fibronectin-derived arginine-glycine
      aspartic acid-serine (RGDS) sequence, in order to achieve a biofunctional PEG
      hydrogel layer around the nanoparticles. RGDS-bound PEG hydrogel-coated MIONPs
      showed a 17-fold higher uptake by the human cervical cancer HeLa cell line than
      that of amine-coated MIONPs. This novel method allows for the coating of MIONPs
      with nano-thin biofunctional hydrogel layers that may prevent undesirable cell
      and protein adhesion and may allow for cellular uptake in target tissues in a
      specific manner. These findings indicate that the further biofunctional PEG
      hydrogel coating of MIONPs is a promising platform for enhanced specific cell
      targeting in biomedical imaging and cancer therapy.

PMID- 22619532
TI  - Nanofibrous poly(lactide-co-glycolide) membranes loaded with diamond
      nanoparticles as promising substrates for bone tissue engineering.
AB  - BACKGROUND: Nanofibrous scaffolds loaded with bioactive nanoparticles are
      promising materials for bone tissue engineering. METHODS: In this study,
      composite nanofibrous membranes containing a copolymer of L-lactide and glycolide
      (PLGA) and diamond nanoparticles were fabricated by an electrospinning technique.
      PLGA was dissolved in a mixture of methylene chloride and dimethyl formamide
      (2:3) at a concentration of 2.3 wt%, and nanodiamond (ND) powder was added at a
      concentration of 0.7 wt% (about 23 wt% in dry PLGA). RESULTS: In the composite
      scaffolds, the ND particles were either arranged like beads in the central part
      of the fibers or formed clusters protruding from the fibers. In the PLGA-ND
      membranes, the fibers were thicker (diameter 270 +/- 9 nm) than in pure PLGA
      meshes (diameter 218 +/- 4 nm), but the areas of pores among these fibers were
      smaller than in pure PLGA samples (0.46 +/- 0.02 MUm(2) versus 1.28 +/- 0.09
      MUm(2) in pure PLGA samples). The PLGA-ND membranes showed higher mechanical
      resistance, as demonstrated by rupture tests of load and deflection of rupture
      probe at failure. Both types of membranes enabled the attachment, spreading, and
      subsequent proliferation of human osteoblast-like MG-63 cells to a similar
      extent, although these values were usually lower than on polystyrene dishes.
      Nevertheless, the cells on both types of membranes were polygonal or spindle-like
      in shape, and were distributed homogeneously on the samples. From days 1-7 after
      seeding, their number rose continuously, and at the end of the experiment, these
      cells were able to create a confluent layer. At the same time, the cell
      viability, evaluated by a LIVE/DEAD viability/cytotoxicity kit, ranged from 92%
      to 97% on both types of membranes. In addition, on PLGA-ND membranes, the cells
      formed well developed talin-containing focal adhesion plaques. As estimated by
      the determination of tumor necrosis factor-alpha levels in the culture medium and
      concentration of intercellular adhesion molecule-1, MG-63 cells, and RAW 264.7
      macrophages on these membranes did not show considerable inflammatory activity.
      CONCLUSION: This study shows that nanofibrous PLGA membranes loaded with diamond
      nanoparticles have interesting potential for use in bone tissue engineering.

PMID- 22619533
TI  - Luminescent single-walled carbon nanotube-sensitized europium nanoprobes for
      cellular imaging.
AB  - Lanthanoid-based optical probes with excitation wavelengths in the ultra-violet
      (UV) range (300-325 nm) have been widely developed as imaging probes. Efficient
      cellular imaging requires that lanthanoid optical probes be excited at visible
      wavelengths, to avoid UV damage to cells. The efficacy of europium-catalyzed
      single-walled carbon nanotubes (Eu-SWCNTs), as visible nanoprobes for cellular
      imaging, is reported in this study. Confocal fluorescence microscopy images of
      breast cancer cells (SK-BR-3 and MCF-7) and normal cells (NIH 3T3), treated with
      Eu-SWCNT at 0.2 MUg/mL concentration, showed bright red luminescence after
      excitation at 365 nm and 458 nm wavelengths. Cell viability analysis showed no
      cytotoxic effects after the incubation of cells with Eu-SWCNTs at this
      concentration. Eu-SWCNT uptake is via the endocytosis mechanism. Labeling
      efficiency, defined as the percentage of incubated cells that uptake Eu-SWCNT,
      was 95%-100% for all cell types. The average cellular uptake concentration was
      6.68 ng Eu per cell. Intracellular localization was further corroborated by
      transmission electron microscopy and Raman microscopy. The results indicate that
      Eu-SWCNT shows potential as a novel cellular imaging probe, wherein SWCNT
      sensitizes Eu(3+) ions to allow excitation at visible wavelengths, and stable
      time-resolved red emission. The ability to functionalize biomolecules on the
      exterior surface of Eu-SWCNT makes it an excellent candidate for targeted
      cellular imaging.

PMID- 22619534
TI  - Concentration- and time-dependent response of human gingival fibroblasts to
      fibroblast growth factor 2 immobilized on titanium dental implants.
AB  - BACKGROUND: Titanium (Ti) implants are widely used clinically, but peri
      implantitis remains one of the most common and serious complications. Healthy
      integration between gingival tissue and the implant surface is critical to long
      term success in dental implant therapy. The objective of this study was to
      investigate how different concentrations of immobilized fibroblast growth factor
      2 (FGF2) on the titania nanotubular surface influence the response of human
      gingival fibroblasts (HGFs). METHODS: Pure Ti metal was anodized at 20 V to form
      a vertically organized titanium dioxide nanotube array on which three
      concentrations of FGF2 (250 ng/mL, 500 ng/mL, or 1000 ng/mL) were immobilized by
      repeated lyophilization. Surface topography was observed and FGF2 elution was
      detected using enzyme-linked immunosorbent assay. The bioactivity changes of
      dissolvable immobilized FGF2 were measured by methyl-thiazolyl-tetrazolium assay.
      Behavior of HGFs was evaluated using adhesion and methyl-thiazolyl-tetrazolium
      bromide assays. RESULTS: The FGF2 remained for several days on the modified
      surface on which HGFs were cultured. Over 90% of the dissolvable immobilized FGF2
      had been eluted by Day 9, whereas the FGF2 activity was found to diminish
      gradually from Day 1 to Day 9. The titania nanotubular surface with an optimal
      preparing concentration (500 ng/mL) of FGF2 immobilization exhibited improved HGF
      functions such as cellular attachment, proliferation, and extracellular matrix
      related gene expression. Moreover, significant bidirectional as well as
      concentration- and time-dependent bioactivity was observed. CONCLUSION: Synergism
      of the FGF2-impregnated titanium dioxide nanotubular surface revealed good
      gingival-implant integration, indicating that these materials might have
      promising applications in dentistry and other biomedical devices.

PMID- 22619535
TI  - Coseeded Schwann cells myelinate neurites from differentiated neural stem cells
      in neurotrophin-3-loaded PLGA carriers.
AB  - Biomaterials and neurotrophic factors represent promising guidance for neural
      repair. In this study, we combined poly-(lactic acid-co-glycolic acid) (PLGA)
      conduits and neurotrophin-3 (NT-3) to generate NT-3-loaded PLGA carriers in
      vitro. Bioactive NT-3 was released stably and constantly from PLGA conduits for
      up to 4 weeks. Neural stem cells (NSCs) and Schwann cells (SCs) were coseeded
      into an NT-releasing scaffold system and cultured for 14 days. Immunoreactivity
      against Map2 showed that most of the grafted cells (>80%) were differentiated
      toward neurons. Double-immunostaining for synaptogenesis and myelination revealed
      the formation of synaptic structures and myelin sheaths in the coculture, which
      was also observed under electron microscope. Furthermore, under depolarizing
      conditions, these synapses were excitable and capable of releasing synaptic
      vesicles labeled with FM1-43 or FM4-64. Taken together, coseeding NSCs and SCs
      into NT-3-loaded PLGA carriers increased the differentiation of NSCs into
      neurons, developed synaptic connections, exhibited synaptic activities, and
      myelination of neurites by the accompanying SCs. These results provide an
      experimental basis that supports transplantation of functional neural
      construction in spinal cord injury.

PMID- 22619536
TI  - Feasibility studies for assaying alpha-fetoprotein using antibody-activated
      magnetic nanoparticles.
AB  - Some previous reports have already shown the characterizations of immunomagnetic
      reduction (IMR). The assay technology involves the utilities of biofunctionalized
      magnetic nanoparticles to label target biomolecules. However, the detection
      threshold and interference tests for IMR have not been investigated in detail. In
      this study, alpha-fetoprotein (AFP) was used as a target biomolecule. The signals
      for AFP solutions of various concentrations, or with interfering materials, were
      detected via IMR. These samples were also used for characterizing the detection
      threshold and interference with enzyme-linked immunosorbent assay (ELISA). The
      results of assaying AFP level with IMR and ELISA were compared. The detection
      threshold for assaying AFP with IMR was found to be 3 ng/mL, which is 15 times
      lower than that of ELISA, and definitely suppresses false negative. For the
      interfering materials noted commonly in serum such as hemoglobin, bilirubin,
      triglyceride, and vascular endothelial growth factor, there was no detectable
      interfering effect when assaying AFP with IMR. Several serum samples from normal
      people and liver-tumor-bearing patients were used for the detections of AFP
      concentration via IMR. These results reveal the feasibilities of assaying AFP in
      blood using IMR, as well as achieving high-sensitive and high-specific assay for
      AFP.

PMID- 22619537
TI  - 5-aminolevulinic acid-incorporated poly(vinyl alcohol) nanofiber-coated metal
      stent for application in photodynamic therapy.
AB  - BACKGROUND: The study investigated the use of combined photodynamic therapy (PDT)
      and stent placement for the treatment of cholangiocarcinoma (CC). For this
      purpose, 5-aminolevulinic acid (ALA) was incorporated into poly(vinyl alcohol)
      (PVA) nanofiber, and coated onto metal stents. Their efficacy was assessed in PDT
      towards HuCC-T1 CC cells. METHODS: Fabrication of ALA-PVA nanofiber, and
      simultaneous coating onto metal stents, was performed through electrospinning.
      The dark-toxicity, generation of protoporphyrin IX (PpIX), and PDT effect of ALA
      and ALA-PVA nanofiber were studied in vitro, using HuCC-T1 CC cells. RESULTS: The
      ALA-PVA nanofibers were coated onto metal stents less than 1000 nm in diameter.
      ALA-only displayed marginal cytotoxicity; ALA-PVA nanofiber showed less
      cytotoxicity. PpIX generation was not sigficantly different between ALA and ALA
      PVA nanofiber treatments. PVA itself did not generate PpIX in tumor cells. ALA
      and ALA-PVA nanofiber displayed a similar PDT effect on tumor cells. Cell
      viability was decreased, dose-dependently, until ALA concentration reached 100
      MUg/mL. Necrosis and apoptosis of tumor cells occurred similarly for ALA and ALA-
      PVA nanofiber treatments. CONCLUSION: The ALA-PVA nanofiber-coated stent is a
      promising candidate for therapeutic use with cholangiocarcinoma.

PMID- 22619538
TI  - Peptide-modified liposomes for selective targeting of bombesin receptors
      overexpressed by cancer cells: a potential theranostic agent.
AB  - OBJECTIVES: Drug delivery systems consisting of liposomes displaying a cell
      surface receptor-targeting peptide are being developed to specifically deliver
      chemotherapeutic drugs to tumors overexpressing a target receptor. This study
      addresses novel liposome composition approaches to specifically target tissues
      overexpressing bombesin (BN) receptors. METHODS: A new amphiphilic peptide
      derivative (MonY-BN) containing the BN(7-14) peptide, the DTPA
      (diethylenetriaminepentaacetate) chelating agent, a hydrophobic moiety with two
      C(18) alkyl chains, and polyethylene glycol spacers, has been synthesized by
      solid-phase methods. Liposomes have been generated by co-aggregation of MonY-BN
      with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). The structural and
      biological properties of these new target-selective drug-delivery systems have
      been characterized. RESULTS: Liposomes with a DSPC/MonY-BN (97/3 molar ratio)
      composition showed a diameter of 145.5 +/- 31.5 nm and a polydispersity index of
      0.20 +/- 0.05. High doxorubicin (Dox) loading was obtained with the remote pH
      gradient method using citrate as the inner buffer. Specific binding to PC-3 cells
      of DSPC/MonY-BN liposomes was obtained (2.7% +/- 0.3%, at 37 degrees C), compared
      with peptide-free DSPC liposomes (1.4% +/- 0.2% at 37 degrees C). Incubation of
      cells with DSPC/ MonY-BN/Dox showed significantly lower cell survival compared
      with DSPC/Dox-treated cells, in the presence of 100 ng/mL and 300 ng/mL drug
      amounts, in cytotoxicity experiments. Intravenous treatment of PC-3 xenograft
      bearing mice with DSPC/MonY-BN/Dox at 10 mg/kg Dox dose produced higher tumour
      growth inhibition (60%) compared with nonspecific DSPC/ Dox liposomes (36%)
      relative to control animals. CONCLUSION: The structural and loading properties of
      DSPC/MonY-BN liposomes along with the observed in-vitro and in-vivo activity are
      encouraging for further development of this approach for target-specific cancer
      chemotherapy.

PMID- 22619539
TI  - Comparison of two kinds of nanomedicine for targeted gene therapy: premodified or
      postmodified gene delivery systems.
AB  - BACKGROUND: The applications of ligand-polyethylene glycol (PEG)-modified
      nanocarriers have now emerged, as well as recognized strategies to provide the
      vectors with active targeting properties. In this research, premodification and
      postmodification were compared using the same ligand, ie, a novel conjugated
      mannan-containing PEG and L-alpha-phosphatidylethanolamine (PE). METHODS:
      Premodified and postmodified solid lipid nanoparticles were prepared and the
      characteristics of the two kinds of vehicles were evaluated. The modified vectors
      were then administered intravenously to rats and the in vivo targeting behavior
      of the complexes was investigated in liver macrophages. RESULTS: By carefully
      formulating the carriers with an optimal ratio of mannan-containing PEG-PE,
      postmodified vehicles displayed more efficient gene expression in rat Kupffer
      cells both in vitro and in vivo. CONCLUSION: Postmodified gene carriers are
      superior to premodified gene vectors, although the latter is also promising for
      targeted gene delivery. This discovery could guide our future research.

PMID- 22619540
TI  - Preparation and characterization of solid lipid nanoparticles loaded with
      frankincense and myrrh oil.
AB  - The aim of the present study was to prepare solid lipid nanoparticles (SLNs) for
      the oral delivery of frankincense and myrrh essential oils (FMO). Aqueous
      dispersions of SLNs were successfully prepared by a high-pressure homogenization
      method using Compritol 888 ATO as the solid lipid and soybean lecithin and Tween
      80 as the surfactants. The properties of the SLNs such as particle size, zeta
      potential (ZP), and drug encapsulation efficiency (EE) were investigated. The
      morphology of SLNs was observed by transmission electron microscopy (TEM). The
      crystallinity of the formulation was analyzed by differential scanning
      calorimetry (DSC) and X-ray diffraction (XRD). In addition, drug evaporation
      release and antitumor activity were also studied. Round SLNs with a mean size of
      113.3 +/- 3.6 nm, a ZP of -16.8 +/- 0.4 mV, and an EE of 80.60% +/- 1.11% were
      obtained. DSC and XRD measurements revealed that less ordered structures were
      formed in the inner cores of the SLN particles. Evaporation loss of the active
      components in FMO could be reduced in the SLNs. Furthermore, the SLN formulation
      increased the antitumor efficacy of FMO in H22-bearing Kunming mice. Hence, the
      presented SLNs can be used as drug carriers for hydrophobic oil drugs extracted
      from traditional Chinese medicines.

PMID- 22619541
TI  - Cellular entry of nanoparticles via serum sensitive clathrin-mediated
      endocytosis, and plasma membrane permeabilization.
AB  - Increasing production and application of nanomaterials raises significant
      questions regarding the potential for cellular entry and toxicity of
      nanoparticles. It was observed that the presence of serum reduces the cellular
      association of 20 nm carboxylate-modified fluorescent polystyrene beads up to 20
      fold, relative to cells incubated in serum-free media. Analysis by confocal
      microscopy demonstrated that the presence of serum greatly reduces the cell
      surface association of nanoparticles, as well as the potential for
      internalization. However, both in the presence and absence of serum, nanoparticle
      entry depends upon clathrin-mediated endocytosis. Finally, experiments performed
      with cells cooled to 4 degrees C suggest that a proportion of the accumulation of
      nanoparticles in cells was likely due to direct permeabilization of the plasma
      membrane.

PMID- 22619542
TI  - Real-time detection of implant-associated neutrophil responses using a formyl
      peptide receptor-targeting NIR nanoprobe.
AB  - Neutrophils play an important role in implant-mediated inflammation and
      infection. Unfortunately, current methods which monitor neutrophil activity,
      including enzyme measurements and histological evaluation, require many animals
      and cannot be used to accurately depict the dynamic cellular responses. To
      understand the neutrophil interactions around implant-mediated inflammation and
      infection it is critical to develop methods which can monitor in vivo cellular
      activity in real time. In this study, formyl peptide receptor (FPR)-targeting
      near-infrared nanoprobes were fabricated. This was accomplished by conjugating
      near-infrared dye with specific peptides having a high affinity to the FPRs
      present on activated neutrophils. The ability of FPR-targeting nanoprobes to
      detect and quantify activated neutrophils was assessed both in vitro and in vivo.
      As expected, FPR-targeting nanoprobes preferentially accumulated on activated
      neutrophils in vitro. Following transplantation, FPR-targeting nanoprobes
      preferentially accumulated at the biomaterial implantation site. Equally
      important, a strong relationship was observed between the extent of fluorescence
      intensity in vivo and the number of recruited neutrophils at the implantation
      site. Furthermore, FPR-targeting nanoprobes may be used to detect and quantify
      the number of neutrophils responding to a catheter-associated infection. The
      results show that FPR-targeting nanoprobes may serve as a powerful tool to
      monitor and measure the extent of neutrophil responses to biomaterial implants in
      vivo.

PMID- 22619543
TI  - Nanoengineered drug-releasing Ti wires as an alternative for local delivery of
      chemotherapeutics in the brain.
AB  - The blood-brain barrier (BBB) blocks the passage of active molecules from the
      blood which makes drug delivery to the brain a challenging problem. Oral drug
      delivery using chemically modified drugs to enhance their transport properties or
      remove the blocking of drug transport across the BBB is explored as a common
      approach to address these problems, but with limited success. Local delivery of
      drugs directly to the brain interstitium using implants such as polymeric wafers,
      gels, and catheters has been recognized as a promising alternative particularly
      for the treatment of brain cancer (glioma) and neurodegenerative disorders. The
      aim of this study was to introduce a new solution by engineering a drug-releasing
      implant for local drug delivery in the brain, based on titanium (Ti) wires with
      titania nanotube (TNT) arrays on their surfaces. Drug loading and drug release
      characteristics of this system were explored using two drugs commonly used in
      oral brain therapy: dopamine (DOPA), a neurotransmitter agent; and doxorubicin
      (DOXO), an anticancer drug. Results showed that TNT/Ti wires could provide a
      considerable amount of drugs (>170 MUg to 1000 MUg) with desirable release
      kinetics and controllable release time (1 to several weeks) and proved their
      feasibility for use as drug-releasing implants for local drug delivery in the
      brain. PURPOSE: In this report, a new drug-releasing platform in the form of
      nanoengineered Ti wires with TNT arrays is proposed as an alternative for local
      delivery of chemotherapeutics in the brain to bypass the BBB. To prove this
      concept, drug loading and release characteristics of two drugs important for
      brain therapy (the neurotransmitter DOPA and the anticancer drug DOXO) were
      explored. METHODS: Titania nanotube arrays on the surface of Ti wires (TNT/Ti)
      were fabricated using a simple anodization process, followed by separate loading
      of two drugs (DOPA and DOXO) inside the nanotube structures. The loading and in
      vitro release characteristics of prepared TNT/Ti implants were examined using
      thermogravimetric analysis (TGA) UV-Vis spectroscopy. RESULTS: Scanning electron
      microscopy studies confirmed that well-ordered, vertically aligned, densely
      packed nanotube arrays with an average diameter of 170 nm and length 70 MUm were
      formed on the surface of TNT/Ti wires. TGA results showed a total drug loading of
      170 MUg and 1200 MUg inside the TNTs for DOPA and DOXO respectively. Two-phase
      drug release behavior was observed including a fast release (burst) for the first
      6 hours and a prolonged slow release phase for 8 days, both with acceptable
      dosage and desirable release kinetics. The physical, structural, loading and
      release characteristics of prepared TNT/Ti implants showed several advantages in
      comparison with existing and clinically proved brain implants. CONCLUSION: Our
      results confirmed that TNT/Ti wires can be successfully employed as a suitable
      platform to release neurotransmitters such as DOPA and anticancer drugs such as
      DOXO. Hence, they are a feasible alternative as drug-releasing implants for local
      drug delivery in the brain to combat neurodegenerative disorders or brain tumors.

PMID- 22619544
TI  - Controlled-release levodopa methyl ester/benserazide-loaded nanoparticles
      ameliorate levodopa-induced dyskinesia in rats.
AB  - BACKGROUND: Levodopa remains the most effective drug in the treatment of
      Parkinson's disease. However, long-term administration of levodopa induces motor
      complications, such as levodopa-induced dyskinesia. The mechanisms underlying
      levodopa-induced dyskinesia are not fully understood. METHODS: In this study, we
      prepared levodopa methyl ester (LDME)/benserazide-loaded nanoparticles, which can
      release LDME and benserazide in a sustained manner. Dyskinesia was induced in
      rats by repeated administration of levodopa then treated with LDME plus
      benserazide or the same dose of LDME/benserazide-loaded nanoparticles.
      Apomorphine- induced rotations and abnormal involuntary movements (AIMs) were
      measured on treatment days 1, 5, 10, 15, and 20. In addition, the levels of
      phosphorylated dopamine- and cyclic adenosine monophosphate- regulated
      phosphoprotein of 32 kDa, extracellular signal-regulated kinases 1/2, and
      DeltafosB were determined by Western blot. Tau levels were determined by Western
      blot and immunohistochemistry. Dynorphin levels in the striatum and cortex of
      rats were measured using enzyme-linked immunosorbent assay. RESULTS: Over the
      course of levodopa treatment, the rats developed abnormal AIMs, classified as
      locomotive, axial, orolingual, and forelimb dyskinesia. The degree of reduction
      of apomorphine-induced rotations was comparable in dyskinetic rats treated with
      LDME plus benserazide or LDME/benserazide-loaded nanoparticles. The axial, limb,
      and orolingual (ALO) AIMs of dyskinetic rats treated with LDME/benserazide-loaded
      nanoparticles were 14 +/- 2.5, 9 +/- 2.0, and 10 +/- 2.1 on treatment days 10,
      15, and 20, respectively, which were significantly reduced compared with
      dyskinetic rats treated with LDME plus benserazide (25 +/- 3.7, 27 +/- 3.8, and
      25 +/- 3.5, respectively). The locomotive AIMs of dyskinetic rats treated with
      LDME/benserazide-loaded nanoparticles were 2.3 +/- 0.42, 1.7 +/- 0.35, and 1.6 +/
      0.37 on treatment days 10, 15, and 20, respectively, which were also reduced
      compared with dyskinetic rats treated with LDME plus benserazide (4.4 +/- 0.85,
      4.7 +/- 0.95 and 4.8 +/- 0.37, respectively). Western blot showed that the levels
      of phosphorylated dopamine- and cyclic adenosine monophosphate-regulated
      phosphoprotein of 32 kDa, extracellular signal-regulated kinases 1/2, tau, and
      DeltafosB in dyskinetic rats treated with LDME/benserazide-loaded nanoparticles
      were 134.6 +/- 14.1, 174.9 +/- 15.1, 134.2 +/- 19.3, and 320.5 +/- 32.8,
      respectively, which were significantly reduced compared with those of dyskinetic
      rats treated with LDME plus benserazide (210.3 +/- 19.7, 320.8 +/- 21.9, 340.4 +/
      27.1, and 620.7 +/- 48.3, respectively). Immunohistochemistry indicated that the
      level of phosphorylated tau was (7.2 +/- 1.1) * 10(4) in dyskinetic rats treated
      with LDME/benserazide-loaded nanoparticles. However, the tau level was only (14.6
      +/- 2.3) * 10(4) in LDME plus benserazide-treated dyskinetic rats. There was a
      significant difference between the two groups. Enzyme-linked immunosorbent assay
      showed that dynorphin levels in the striatum and cortex of dyskinetic rats
      treated with LDME/benserazide-loaded nanoparticles were 5.7 +/- 1.2 and 4.8 +/-
      0.87, respectively, which were significantly reduced compared with LDME plus
      benserazide-treated dyskinetic rats (13.3 +/- 2.1 and 8.1 +/- 1.1 for the
      striatum and cortex, respectively). CONCLUSION: Results suggest that
      LDME/benserazide-loaded nanoparticles can be used to reduce the expression of
      dyskinesia in dyskinetic rats.

PMID- 22619545
TI  - Biomimetic three-dimensional nanocrystalline hydroxyapatite and magnetically
      synthesized single-walled carbon nanotube chitosan nanocomposite for bone
      regeneration.
AB  - BACKGROUND: Many shortcomings exist in the traditional methods of treating bone
      defects, such as donor tissue shortages for autografts and disease transmission
      for allografts. The objective of this study was to design a novel three
      dimensional nanostructured bone substitute based on magnetically synthesized
      single-walled carbon nanotubes (SWCNT), biomimetic hydrothermally treated
      nanocrystalline hydroxyapatite, and a biocompatible hydrogel (chitosan). Both
      nanocrystalline hydroxyapatite and SWCNT have a biomimetic nanostructure,
      excellent osteoconductivity, and high potential to improve the load-bearing
      capacity of hydrogels. METHODS: Specifically, three-dimensional porous chitosan
      scaffolds with different concentrations of nanocrystalline hydroxyapatite and
      SWCNT were created to support the growth of human osteoblasts (bone-forming
      cells) using a lyophilization procedure. Two types of SWCNT were synthesized in
      an arc discharge with a magnetic field (B-SWCNT) and without a magnetic field (N
      SWCNT) for improving bone regeneration. RESULTS: Nanocomposites containing
      magnetically synthesized B-SWCNT had superior cytocompatibility properties when
      compared with nonmagnetically synthesized N-SWCNT. B-SWCNT have much smaller
      diameters and are twice as long as their nonmagnetically prepared counterparts,
      indicating that the dimensions of carbon nanotubes can have a substantial effect
      on osteoblast attachment. CONCLUSION: This study demonstrated that a chitosan
      nanocomposite with both B-SWCNT and 20% nanocrystalline hydroxyapatite could
      achieve a higher osteoblast density when compared with the other experimental
      groups, thus making this nanocomposite promising for further exploration for bone
      regeneration.

PMID- 22619546
TI  - Egg white-mediated green synthesis of silver nanoparticles with excellent
      biocompatibility and enhanced radiation effects on cancer cells.
AB  - A simple, cost-effective, and environmentally friendly approach to the aqueous
      phase synthesis of silver (Ag) nanoparticles was demonstrated using silver
      nitrate (AgNO(3)) and freshly extracted egg white. The bio-conjugates were
      characterized by UV-visible spectroscopy, transmission electron microscopy,
      Fourier transform infrared spectrometry, and dynamic light scattering. These
      results indicated that biomolecule-coated Ag nanoparticles are predominantly
      spherical in shape with an average size of 20 nm. The proteins of egg white,
      which have different functional groups, played important roles in reducing Ag(+)
      and maintaining product attributes such as stability and dispersity. In vitro
      cytotoxicity assays showed that these Ag-protein bio-conjugates showed good
      biocompatibility with mouse fibroblast cell lines 3T3. Furthermore, X-ray
      irradiation tests on 231 tumor cells suggested that the biocompatible Ag-protein
      bio-conjugates enhanced the efficacy of irradiation, and thus may be promising
      candidates for use during cancer radiation therapy.

PMID- 22619547
TI  - Zerovalent bismuth nanoparticles inhibit Streptococcus mutans growth and
      formation of biofilm.
AB  - BACKGROUND AND METHODS: Despite continuous efforts, the increasing prevalence of
      resistance among pathogenic bacteria to common antibiotics has become one of the
      most significant concerns in modern medicine. Nanostructured materials are used
      in many fields, including biological sciences and medicine. While some bismuth
      derivatives has been used in medicine to treat vomiting, nausea, diarrhea, and
      stomach pain, the biocidal activity of zerovalent bismuth nanoparticles has not
      yet been studied. The objective of this investigation was to analyze the
      antimicrobial activity of bismuth nanoparticles against oral bacteria and their
      antibiofilm capabilities. RESULTS: Our results showed that stable colloidal
      bismuth nanoparticles had 69% antimicrobial activity against Streptococcus mutans
      growth and achieved complete inhibition of biofilm formation. These results are
      similar to those obtained with chlorhexidine, the most commonly used oral
      antiseptic agent. The minimal inhibitory concentration of bismuth nanoparticles
      that interfered with S. mutans growth was 0.5 mM. CONCLUSION: These results
      suggest that zerovalent bismuth nanoparticles could be an interesting
      antimicrobial agent to be incorporated into an oral antiseptic preparation.

PMID- 22619548
TI  - Towards development of novel immunization strategies against leishmaniasis using
      PLGA nanoparticles loaded with kinetoplastid membrane protein-11.
AB  - BACKGROUND: Vaccine development has been a priority in the fight against
      leishmaniases, which are vector-borne diseases caused by Leishmania protozoa.
      Among the different immunization strategies employed to date is inoculation of
      plasmid DNA coding for parasite antigens, which has a demonstrated ability to
      induce humoral and cellular immune responses. In this sense, inoculation of
      plasmid DNA encoding Leishmania kinetoplasmid membrane protein-11 (KMP-11) was
      able to confer protection against visceral leishmaniasis. However, recently the
      use of antigen delivery systems such as poly(lactic-co-glycolic acid) (PLGA)
      nanoparticles has also proven effective for eliciting protective immune
      responses. METHODS: In the present work, we tested two immunization strategies
      with the goal of obtaining protection, in terms of lesion development and
      parasite load, against cutaneous leishmaniasis caused by L. braziliensis. One
      strategy involved immunization with plasmid DNA encoding L. infantum chagasi KMP
      11. Alternatively, mice were primed with PLGA nanoparticles loaded with the
      recombinant plasmid DNA and boosted using PLGA nanoparticles loaded with
      recombinant KMP-11. RESULTS: Both immunization strategies elicited detectable
      cellular immune responses with the presence of both proinflammatory and anti
      inflammatory cytokines; mice receiving the recombinant PLGA nanoparticle
      formulations also demonstrated anti-KMP-11 IgG1 and IgG2a. Mice were then
      challenged with L. braziliensis, in the presence of sand fly saliva. Lesion
      development was not inhibited following either immunization strategy. However,
      immunization with PLGA nanoparticles resulted in a more prominent reduction in
      parasite load at the infection site when compared with immunization using plasmid
      DNA alone. This effect was associated with a local increase in interferon-gamma
      and in tumor necrosis factor-alpha. Both immunization strategies also resulted in
      a lower parasite load in the draining lymph nodes, albeit not significantly.
      CONCLUSION: Our results encourage the pursuit of immunization strategies
      employing nanobased delivery systems for vaccine development against cutaneous
      leishmaniasis caused by L. braziliensis infection.

PMID- 22619549
TI  - Controlled release and angiotensin-converting enzyme inhibition properties of an
      antihypertensive drug based on a perindopril erbumine-layered double hydroxide
      nanocomposite.
AB  - BACKGROUND: The intercalation of perindopril erbumine into Zn/Al-NO(3)-layered
      double hydroxide resulted in the formation of a host-guest type of material. By
      virtue of the ion-exchange properties of layered double hydroxide, perindopril
      erbumine was released in a sustained manner. Therefore, this intercalated
      material can be used as a controlled-release formulation. RESULTS: Perindopril
      was intercalated into the interlayers and formed a well ordered, layered organic
      inorganic nanocomposite. The basal spacing of the products was expanded to 21.7 A
      and 19.9 A by the ion-exchange and coprecipitation methods, respectively, in a
      bilayer and a monolayer arrangement, respectively. The release of perindopril
      from the nanocomposite synthesized by the coprecipitation method was slower than
      that of its counterpart synthesized by the ion-exchange method. The rate of
      release was governed by pseudo-second order kinetics. An in vitro
      antihypertensive assay showed that the intercalation process results in
      effectiveness similar to that of the antihypertensive properties of perindopril.
      CONCLUSION: Intercalated perindopril showed better thermal stability than its
      free counterpart. The resulting material showed sustained-release properties and
      can therefore be used as a controlled-release formulation.

PMID- 22619550
TI  - Ultrasound sonication with microbubbles disrupts blood vessels and enhances tumor
      treatments of anticancer nanodrug.
AB  - Ultrasound (US) sonication with microbubbles (MBs) has the potential to disrupt
      blood vessels and enhance the delivery of drugs into the sonicated tissues. In
      this study, mouse ear tumors were employed to investigate the therapeutic effects
      of US, MBs, and pegylated liposomal doxorubicin (PLD) on tumors. Tumors started
      to receive treatments when they grew up to about 15 mm(3) (early stage) with
      injection of PLD 10 mg/kg, or up to 50 mm(3) (medium stage) with PLD 6 (or 4)
      mg/kg. Experiments included the control, PLD alone, PLD + MBs + US, US alone, and
      MBs + US groups. The procedure for the PLD + MBs + US group was that PLD was
      injected first, MB (SonoVue) injection followed, and then US was immediately
      sonicated on the tumor. The results showed that: (1) US sonication with MBs was
      always able to produce a further hindrance to tumor growth for both early and
      medium-stage tumors; (2) for the medium-stage tumors, 6 mg/kg PLD alone was able
      to inhibit their growth, while it did not work for 4 mg/kg PLD alone; (3) with
      the application of MBs + US, 4 mg/kg PLD was able to inhibit the growth of medium
      stage tumors; (4) for early stage tumors after the first treatment with a high
      dose of PLD alone (10 mg/kg), the tumor size still increased for several days and
      then decreased (a biphasic pattern); (5) MBs + US alone was able to hinder the
      growth of early stage tumors, but unable to hinder that of medium stage tumors.
      The results of histological examinations and blood perfusion measurements
      indicated that the application of MBs + US disrupts the tumor blood vessels and
      enhances the delivery of PLD into tumors to significantly inhibit tumor growth.

PMID- 22619551
TI  - Improved performance of diatomite-based dental nanocomposite ceramics using layer
      by-layer assembly.
AB  - To fabricate high-strength diatomite-based ceramics for dental applications, the
      layer-by-layer technique was used to coat diatomite particles with cationic
      [poly(allylamine hydrochloride)] and anionic [poly(sodium 4-styrenesulfonate)]
      polymers to improve the dispersion and adsorption of positively charged nano
      ZrO(2) (zirconia) as a reinforcing agent. The modified diatomite particles had
      reduced particle size, narrower size distribution, and were well dispersed, with
      good adsorption of nano-ZrO(2). To determine the optimum addition levels for nano
      ZrO(2), ceramics containing 0, 20, 25, 30, and 35 wt% nano-ZrO(2) were sintered
      and characterized by the three-point bending test and microhardness test. In
      addition to scanning electron microscopy, propagation phase-contrast synchrotron
      X-ray microtomography was used to examine the internal structure of the ceramics.
      The addition of 30 wt% nano-ZrO(2) resulted in the highest flexural strength and
      fracture toughness with reduced porosity. Shear bond strength between the core
      and veneer of our diatomite ceramics and the most widely used dental ceramics
      were compared; the shear bond strength value for the diatomite-based ceramics was
      found to be significantly higher than for other groups (P < 0.05). Our results
      show that diatomite-based nanocomposite ceramics are good potential candidates
      for ceramic-based dental materials.

PMID- 22619552
TI  - Effect of supercritical fluid density on nanoencapsulated drug particle size
      using the supercritical antisolvent method.
AB  - The reported work demonstrates and discusses the effect of supercritical fluid
      density (pressure and temperature of supercritical fluid carbon dioxide) on
      particle size and distribution using the supercritical antisolvent (SAS) method
      in the purpose of drug encapsulation. In this study, paracetamol was encapsulated
      inside L-polylactic acid, a semicrystalline polymer, with different process
      parameters, including pressure and temperature, using the SAS process. The
      morphology and particle size of the prepared nanoparticles were determined by
      scanning electron microscopy and transmission electron microscopy. The results
      revealed that increasing temperature enhanced mean particle size due to the
      plasticizing effect. Furthermore, increasing pressure enhanced molecular
      interaction and solubility; thus, particle size was reduced. Transmission
      electron microscopy images defined the internal structure of nanoparticles.
      Thermal characteristics of nanoparticles were also investigated via differential
      scanning calorimetry. Furthermore, X-ray diffraction pattern revealed the changes
      in crystallinity structure during the SAS process. In vitro drug release analysis
      determined the sustained release of paracetamol in over 4 weeks.

PMID- 22619553
TI  - A facile inhibitor screening of SARS coronavirus N protein using nanoparticle
      based RNA oligonucleotide.
AB  - Hundreds of million people worldwide have been infected with severe acute
      respiratory syndrome (SARS), and the rate of global death from SARS has
      remarkably increased. Hence, the development of efficient drug treatments for the
      biological effects of SARS is highly needed. We have previously shown that
      quantum dots (QDs)-conjugated RNA oligonucleotide is sensitive to the specific
      recognition of the SARS-associated coronavirus (SARS-CoV) nucleocapsid (N)
      protein. In this study, we found that a designed biochip could analyze inhibitors
      of the SARS-CoV N protein using nanoparticle-based RNA oligonucleotide. Among the
      polyphenolic compounds examined, (-)-catechin gallate and (-)-gallocatechin
      gallate demonstrated a remarkable inhibition activity on SARS-CoV N protein. (-)
      catechin gallate and (-)-gallocatechin gallate attenuated the binding affinity in
      a concentrated manner as evidenced by QDs-conjugated RNA oligonucleotide on a
      designed biochip. At a concentration of 0.05 MUg mL(-1), (-)-catechin gallate and
      (-)-gallocatechin gallate showed more than 40% inhibition activity on a
      nanoparticle-based RNA oligonucleotide biochip system.

PMID- 22619554
TI  - Structure-dependent immunostimulatory effect of CpG oligodeoxynucleotides and
      their delivery system.
AB  - Unmethylated cytosine-phosphate-guanosine (CpG) oligodeoxynucleotides (ODNs) are
      recognized by Toll-like receptor 9 (TLR9) found in antigen-presenting cells and B
      cells and can activate the immune system. Using CpG ODNs as an adjuvant has been
      found to be effective for treating infectious diseases, cancers, and allergies.
      Because natural ODNs with only a phosphodiester backbone are easily degraded by
      nuclease (deoxyribonuclease [DNase]) in serum, CpG ODNs with a phosphorothioate
      backbone have been studied for clinical application. CpG ODNs with a
      phosphorothioate backbone have raised concern regarding undesirable side effects;
      however, several CpG ODNs with only a phosphodiester backbone have been reported
      to be stable in serum and to show an immunostimulatory effect. In recent years,
      research has been conducted on delivery systems for CpG ODNs using nanoparticles
      (NPs). The advantages of NP-based delivery of CpG ODN include (1) it can protect
      CpG ODN from DNase, (2) it can retain CpG ODN inside the body for a long period
      of time, (3) it can improve the cellular uptake efficiency of CpG ODN, and (4) it
      can deliver CpG ODN to the target tissues. Because the target cells of CpG ODN
      are cells of the immune system and TLR9, the receptor of CpG ODN is localized in
      endolysosomes, CpG ODN delivery systems are required to have qualities different
      from other nucleic acid drugs such as antisense DNA and small interfering RNA.
      Studies until now have reported various NPs as carriers for CpG ODN delivery.
      This review presents DNase-resistant CpG ODNs with various structures and their
      immunostimulatory effects and also focuses on delivery systems of CpG ODNs that
      utilize NPs. Because CpG ODNs interact with TLR9 and activate both the innate and
      the adaptive immune system, the application of CpG ODNs for the treatment of
      cancers, infectious diseases, and allergies holds great promise.

PMID- 22619555
TI  - Preclinical evaluation of injectable sirolimus formulated with polymeric
      nanoparticle for cancer therapy.
AB  - Nanoparticles are useful delivery vehicles for promising drug candidates that
      face obstacles for clinical applicability. Sirolimus, an inhibitor of mammalian
      target of rapamycin has gained attention for targeted anticancer therapy, but its
      clinical application has been limited by its poor solubility. This study was
      designed to enhance the feasibility of sirolimus for human cancer treatment.
      Polymeric nanoparticle (PNP)-sirolimus was developed as an injectable formulation
      and has been characterized by transmission electron microscopy and dynamic light
      scattering. Pharmacokinetic analysis revealed that PNP-sirolimus has prolonged
      circulation in the blood. In addition, PNP-sirolimus preserved the in vitro
      killing effect of free sirolimus against cancer cells, and intravenous
      administration displayed its potent in vivo anticancer efficacy in xenograft
      tumor mice. In addition, PNP-sirolimus enhanced the radiotherapeutic efficacy of
      sirolimus both in vitro and in vivo. Clinical application of PNP-sirolimus is a
      promising strategy for human cancer treatment.

PMID- 22619557
TI  - Influence of nanomaterials on stem cell differentiation: designing an appropriate
      nanobiointerface.
AB  - During the last decade, due to advances in functionalization chemistry, novel
      nanobiomaterials with applications in tissue engineering and regenerative
      medicine have been developed. These novel materials with their unique physical
      and chemical properties are bioactive hierarchical structures that hold great
      promise for future development of human tissues. Thus, various nanomaterials are
      currently being intensively explored in the directed differentiation of stem
      cells, the design of novel bioactive scaffolds, and new research avenues towards
      tissue regeneration. This paper illustrates the latest achievements in the
      applications of nanotechnology in tissue engineering in the field of regenerative
      medicine.

PMID- 22619559
TI  - Catalytically active bovine serum amine oxidase bound to fluorescent and
      magnetically drivable nanoparticles.
AB  - Novel superparamagnetic surface-active maghemite nanoparticles (SAMNs)
      characterized by a diameter of 10 +/- 2 nm were modified with bovine serum amine
      oxidase, which used rhodamine B isothiocyanate (RITC) adduct as a fluorescent
      spacer-arm. A fluorescent and magnetically drivable adduct comprised of bovine
      serum copper-containing amine oxidase (SAMN-RITC-BSAO) that immobilized on the
      surface of specifically functionalized magnetic nanoparticles was developed. The
      multifunctional nanomaterial was characterized using transmission electron
      microscopy, infrared spectroscopy, mass spectrometry, and activity measurements.
      The results of this study demonstrated that bare magnetic nanoparticles form
      stable colloidal suspensions in aqueous solutions. The maximum binding capacity
      of bovine serum amine oxidase was approximately 6.4 mg g(-1) nanoparticles. The
      immobilization procedure reduced the catalytic activity of the native enzyme to
      30% +/- 10% and the Michaelis constant was increased by a factor of 2. We suggest
      that the SAMN-RITC-BSAO complex, characterized by a specific activity of 0.81 IU
      g(-1,) could be used in the presence of polyamines to create a fluorescent
      magnetically drivable H(2)O(2) and aldehydes-producing system. Selective tumor
      cell destruction is suggested as a potential future application of this system.

PMID- 22619558
TI  - Effect of intratumoral administration on biodistribution of 64Cu-labeled
      nanoshells.
AB  - BACKGROUND: Gold nanoshells are excellent agents for photothermal ablation cancer
      therapy and are currently under clinical trial for solid tumors. Previous studies
      showed that passive delivery of gold nanoshells through intravenous
      administration resulted in limited tumor accumulation, which represents a major
      challenge for this therapy. In this report, the impact of direct intratumoral
      administration on the pharmacokinetics and biodistribution of the nanoshells was
      systematically investigated. METHODS: The gold nanoshells were labeled with the
      radionuclide, copper-64 ((64)Cu). Intratumoral infusion of (64)Cu-nanoshells and
      two controls, ie, (64)Cu-DOTA (1,4,7,10-tetraazaciclododecane- 1,4,7,10
      tetraacetic acid) and (64)Cu-DOTA-PEG (polyethylene glycol), as well as
      intravenous injection of (64)Cu-nanoshells were performed in nude rats, each with
      a head and neck squamous cell carcinoma xenograft. The pharmacokinetics was
      determined by radioactive counting of serial blood samples collected from the
      rats at different time points post-injection. Using positron emission
      tomography/computed tomography imaging, the in vivo distribution of (64)Cu
      nanoshells and the controls was monitored at various time points after injection.
      Organ biodistribution in the rats at 46 hours was analyzed by radioactive
      counting and compared between the different groups. RESULTS: The resulting
      pharmacokinetic curves indicated a similar trend between the intratumorally
      injected agents, but a significant difference with the intravenously injected
      (64)Cu-nanoshells. Positron emission tomography images and organ biodistribution
      results on rats after intratumoral administration showed higher retention of
      (64)Cu-nanoshells in tumors and less concentration in other healthy organs, with
      a significant difference from the controls. It was also found that, compared with
      intravenous injection, tumor concentrations of (64)Cu-nanoshells improved
      substantially and were stable at 44 hours post-injection. CONCLUSION: There was a
      higher intratumoral retention of (64)Cu-nanoshells and a lower concentration in
      other healthy tissues, suggesting that intratumoral administration is a
      potentially better approach for nanoshell-based photothermal therapy.

PMID- 22619560
TI  - Multifunctional magnetic Fe3O4 nanoparticles combined with chemotherapy and
      hyperthermia to overcome multidrug resistance.
AB  - BACKGROUND: Multidrug resistance in cancer is a major obstacle for clinical
      therapeutics, and is the reason for 90% of treatment failures. This study
      investigated the efficiency of novel multifunctional Fe(3)O(4) magnetic
      nanoparticles (Fe(3)O(4)-MNP) combined with chemotherapy and hyperthermia for
      overcoming multidrug resistance in an in vivo model of leukemia. METHODS: Nude
      mice with tumor xenografts were randomly divided into a control group, and the
      treatment groups were allocated to receive daunorubicin, 5-bromotetrandrine (5
      BrTet) and daunorubicin, Fe(3)O(4)-MNP, and Fe(3)O(4)-MNP coloaded with
      daunorubicin and 5-bromotetrandrine (Fe(3)O(4)-MNP-DNR-5-BrTet), with
      hyperthermia in an alternating magnetic field. We investigated tumor volume and
      pathology, as well as P-glycoprotein, Bcl-2, Bax, and caspase-3 protein
      expression to elucidate the effect of multimodal treatment on overcoming
      multidrug resistance. RESULTS: Fe(3)O(4)-MNP played a role in increasing tumor
      temperature during hyperthermia. Tumors became significantly smaller, and
      apoptosis of cells was observed in both the Fe(3)O(4)-MNP and Fe(3)O(4)-MNP-DNR-5
      BrTet groups, especially in the Fe(3)O(4)-MNP-DNR-5-BrTet group, while tumor
      volumes in the other groups had increased after treatment for 12 days.
      Furthermore, Fe(3)O(4)-MNP-DNR-5-BrTet with hyperthermia noticeably decreased P
      glycoprotein and Bcl-2 expression, and markedly increased Bax and caspase-3
      expression. CONCLUSION: Fe(3)O(4)-MNP-DNR-5-BrTet with hyperthermia may be a
      potential approach for reversal of multidrug resistance in the treatment of
      leukemia.

PMID- 22619561
TI  - Evaluation of atherosclerotic lesions using dextran- and mannan-dextran-coated
      USPIO: MRI analysis and pathological findings.
AB  - Magnetic resonance imaging (MRI) can detect atherosclerotic lesions containing
      accumulations of ultrasmall superparamagnetic iron oxides (USPIO). Positing that
      improved USPIO with a higher affinity for atherosclerotic plaques would yield
      better plaque images, we performed MRI and histologic studies to compare the
      uptake of dextran- and mannan-dextran-coated USPIO (D-USPIO and DM-USPIO,
      respectively) by the atherosclerotic walls of rabbits. We intravenously injected
      atherosclerotic rabbits with DM-USPIO (n = 5) or D-USPIO (n = 5). Two rabbits
      were the controls. The doses delivered were 0.08 (dose 1) (n = 1), 0.4 (dose 2)
      (n = 1), or 0.8 (dose 3) (n = 3) mmol iron/Kg. The dose 3 rabbits underwent in
      vivo contrast-enhanced magnetic resonance angiography (MRA) before and 5 days
      after USPIO administration. Afterwards, all animals were euthanized, the aortae
      were removed and subjected to in vitro MRI study. The signal-to-noise ratio (SNR)
      of the aortic wall in the same region of interest (ROI) was calculated in both in
      vivo and in vitro studies. Histological assessment through measurement of iron
      positive regions in Prussian blue-stained specimens showed that iron-positive
      regions were significantly larger in rabbits injected with DM- rather than D
      USPIO (P < 0.05) for all doses. In vivo MRA showed that the SNR-reducing effect
      of DM- was greater than that of D-USPIO (P < 0.05). With in vitro MRI scans, SNR
      was significantly lower in rabbits treated with dose 2 of DM-USPIO compared with
      D-USPIO treatment (P < 0.05), and it tended to be lower at dose 3 (P < 0.1). In
      conclusion, we suggest that DM-USPIO is superior to D-USPIO for the study of
      atherosclerotic lesions in rabbits.

PMID- 22619562
TI  - Suppression of lung cancer progression by biocompatible glycerol triacrylate
      spermine-mediated delivery of shAkt1.
AB  - BACKGROUND: Polyethylenimine (PEI)-based nonviral gene-delivery systems are
      commonly employed because of their high transfection efficiency. However, the
      toxic nature of PEI is a significant obstacle in clinical gene therapy. In this
      study, we developed biocompatible glycerol triacrylate-spermine (GT-SPE)
      polyspermine as a nanosized gene carrier for potential lung cancer gene therapy.
      METHODS: The GT-SPE was synthesized using the Michael addition reaction between
      GT and SPE. The molecular weight was characterized using gel permeability
      chromatography multiangle laser light scattering and the composition of the
      polymer was analyzed using proton nuclear magnetic resonance. RESULTS: The GT-SPE
      successfully protected the DNA from nucleases. The average particle size of the
      GT-SPE was 121 nm with a zeta potential of +23.45 mV. The GT-SPE was found to be
      less toxic than PEI for various cell lines, as well as for a murine model.
      Finally, our results showed that the GT-SPE/small hairpin Akt1 (shAkt1) complex
      suppressed lung tumorigenesis in a K-ras(LA1) lung cancer mice model by inducing
      apoptosis through the Akt signaling pathway and cell cycle arrest. Aerosol
      delivered GT-SPE/shAkt1, which reduced matrix metalloproteinase-9 activity and
      suppressed the expression levels of proliferating cell nuclear antigen, as well
      as vascular endothelial growth factors and CD31, which are known proliferation
      and angiogenesis markers, respectively. CONCLUSION: Our data suggest that GT-SPE
      may be a candidate for short hairpin-shaped RNA-based aerosol lung cancer gene
      therapy.

PMID- 22619563
TI  - Small cell lung cancer doubling time and its effect on clinical presentation: a
      concise review.
AB  - Small cell lung cancer (SCLC) is one of many types rapidly growing malignant
      diseases, such as Burkitt's lymphoma and testicular germ cell cancers. At
      present, there is no reliable way to screen for SCLC, and imaging modalities tend
      to be delayed in detecting this type of cancer. The clinical presentation of
      acutely and rapidly growing SCLC can mimic those of pulmonary inflammatory or
      infectious disorders, and in some instances, this delays appropriate management
      and negatively affects patient outcome.

PMID- 22619564
TI  - Embryonic signaling pathways and rhabdomyosarcoma: contributions to cancer
      development and opportunities for therapeutic targeting.
AB  - Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood and
      adolescence, accounting for approximately 7% of childhood cancers. Current
      therapies include nonspecific cytotoxic chemotherapy regimens, radiation therapy,
      and surgery; however, these multimodality strategies are unsuccessful in the
      majority of patients with high-risk disease. It is generally believed that these
      tumors represent arrested or aberrant skeletal muscle development, and,
      accordingly, developmental signaling pathways critical to myogenesis such as
      Notch, WNT, and Hedgehog may represent new therapeutic targets. In this paper, we
      summarize the current preclinical studies linking these embryonic pathways to
      rhabdomyosarcoma tumorigenesis and provide support for the investigation of
      targeted therapies in this embryonic cancer.

PMID- 22619565
TI  - "Malignant" perivascular epithelioid cell neoplasm: risk stratification and
      treatment strategies.
AB  - Purpose. Perivascular epithelioid cell tumors (PEComas) are a rare collection of
      tumors characterized by a myomelanocytic phenotype, and PEComas occurring in
      "nonclassic" anatomic distributions are known as perivascular epithelioid cell
      tumor not otherwise specified (PEComa-NOS). This review aims to compile and
      analyze cases of PEComa-NOS in an effort to better define their natural history.
      Design. We evaluated all 234 cases of PEComa-NOS reported in the English
      literature, extracting information regarding diagnostic features, treatment
      approaches, and outcomes. Multivariate analysis of a number of variables
      evaluable on pathologic review was performed to refine preexisting risk
      stratification criteria. Outcomes for patients receiving nonsurgical treatment
      are also reported. Results. Primary tumor size >=5 cm (P = 0.02) and a high (1/50
      HPF) mitotic rate (P < 0.0001) were the only factors significantly associated
      with recurrence following surgical resection. Cytotoxic chemotherapy and
      radiation therapy have shown little benefit in treating PEComa-NOS; mTOR
      inhibition is emerging as a treatment option. Conclusion. Progress has been made
      in understanding the natural history and molecular biology of PEComa-NOS. This
      review further clarifies risk of recurrence in this disease, allowing clinicians
      to better risk stratify patients. Further work should focus on applying this
      knowledge to making treatment decisions for patients with this disease.

PMID- 22619566
TI  - Thromboembolic Events Associated with Thalidomide and Multimodality Therapy for
      Soft Tissue Sarcomas: Results of RTOG 0330.
AB  - Introduction. RTOG 0330 was developed to address the toxicity of RTOG 9514 and to
      add thalidomide (THAL) to MAID chemoradiation for intermediate/high grade soft
      tissue sarcomas (STSs) and to preoperative radiation (XRT) for low-grade STS.
      Methods. Primary/locally recurrent extremity/trunk STS: >=8 cm, intermediate/high
      grade (cohort A): >5 cm, low grade (cohort B). Cohort A: 3 cycles of neoadjuvant
      MAID, 2 cycles of interdigitated THAL (200 mg/day)/concurrent 22 Gy XRT,
      resection, 12 months of adjuvant THAL. Cohort B: neoadjuvant THAL/concurrent 50
      Gy XRT, resection, 6 months of adjuvant THAL. Planned accrual 44 patients.
      Results. 22 primary STS patients (cohort A/B 15/7). Cohort A/B: median age of
      49/47 years; median tumor size 12.8/10 cm. 100% preoperative THAL/XRT and
      surgical resection. Three cycles of MAID were delivered in 93% cohort A. Positive
      margins: 27% cohort A/29% cohort B. Adjuvant THAL: 60% cohort A/57% cohort B.
      Grade 3/4 venous thromboembolic (VTE) events: 40% cohort A (1 catheter thrombus
      and 5 DVT or PE) versus 0% cohort B. RTOG 0330 closed early due to cohort A VTE
      risk and cohort B poor accrual. Conclusion. Neoadjuvant MAID with THAL/XRT was
      associated with increased VTE events not seen with THAL/XRT alone or in RTOG 9514
      with neoadjuvant MAID/XRT.

PMID- 22619567
TI  - Efficacy of phosphatidylinositol-3 kinase inhibitors in a primary mouse model of
      undifferentiated pleomorphic sarcoma.
AB  - Recent advances in sarcoma genomics have identified novel mutations in the PI3K
      pathway in human sarcomas. Here, we use a mouse model of primary soft-tissue
      sarcoma for preclinical testing of doxorubicin and inhibitors of the PI3K
      pathway: BKM120 (PI3K inhibitor) and BEZ235 (a dual PI3K/mTOR inhibitor).
      Doxorubicin-treated tumors (n = 15) showed a partial response rate of 6.6%, just
      as the majority of human sarcomas do not respond to doxorubicin. Treatment with
      BKM120 elicited a partial response in 50% of tumors (n = 10), which was also seen
      in combination with doxorubicin (n = 10). Additionally, BKM120 treatment produced
      a robust delay in tumor growth kinetics. BEZ235-treated tumors (n = 9) showed a
      complete response rate of 11.1%. Combining BEZ235 with doxorubicin (n = 10)
      increased the complete response rate to 50% (P = 0.035). These studies
      demonstrate that PI3K pathway inhibition is a viable and attractive target for
      soft-tissue sarcomas.

PMID- 22619568
TI  - Psidium guajava and Piper betle leaf extracts prolong vase life of cut carnation
      (Dianthus caryophyllus) flowers.
AB  - The effect of leaf extracts of Psidium guajava and Piper betle on prolonging vase
      life of cut carnation flowers was studied. "Carola" and "Pallas Orange" carnation
      flowers, at bud stage, were pulsed 24 hours with a floral preservative. Then,
      flowers were placed in a vase solution containing sprite and a "germicide" (leaf
      extracts of P. guajava and P. betle, 8-HQC, or a copper coin). Flowers treated
      with 8-HQC, copper coin, and leaf extracts had longer vase life, larger flower
      diameter, and higher rate of water uptake compared to control (tap water). The
      leaf extracts of P. guajava and P. betle showed highest antibacterial and
      antifungal activities compared to the other treatments. Both showed similar
      effects on flower quality as the synthetic germicide, 8-HQC. Therefore, these
      extracts are likely natural germicides to prolong vase life of cut flowers.

PMID- 22619569
TI  - Parvovirus B19 infection and severe anemia in renal transplant recipients.
AB  - Kidney transplant (KT) recipients can develop symptomatic Parvovirus (PV) B19
      infections, frequently associated with persistent anemia. The aim of this study
      was to evaluate the prevalence and clinical significance of PV B19 infection in
      anemic and non-anemic KT patients. Overall, out of 64 patients monitored for the
      presence of PV B19 by real-time PCR, 2 (3.12%) had an active PV B19 infection, in
      absence of other viral coinfections. The 2 cases occurred in nonanemic kidney
      transplant patients group (2/50, 4%), while none of the anemic transplant
      patients (0/14) was found to suffer from this infection. Moreover, patients
      affected by active PV B19 infection showed viral loads not exceeding 1 * 10(5)
      genome copies/reaction. In conclusion, in this study, PV B19 infection was not
      common in renal transplant population and wasn't associated with severe anemia.

PMID- 22619571
TI  - Numerical characterization of DNA sequence based on dinucleotides.
AB  - Sequence comparison is a primary technique for the analysis of DNA sequences. In
      order to make quantitative comparisons, one devises mathematical descriptors that
      capture the essence of the base composition and distribution of the sequence.
      Alignment methods and graphical techniques (where each sequence is represented by
      a curve in high-dimension Euclidean space) have been used popularly for a long
      time. In this contribution we will introduce a new nongraphical and nonalignment
      approach based on the frequencies of the dinucleotide XY in DNA sequences. The
      most important feature of this method is that it not only identifies adjacent XY
      pairs but also nonadjacent XY ones where X and Y are separated by some number of
      nucleotides. This methodology preserves information in DNA sequence that is
      ignored by other methods. We test our method on the coding regions of exon-1 of
      beta-globin for 11 species, and the utility of this new method is demonstrated.

PMID- 22619572
TI  - Temporal downscaling of crop coefficient and crop water requirement from growing
      stage to substage scales.
AB  - Crop water requirement is essential for agricultural water management, which is
      usually available for crop growing stages. However, crop water requirement values
      of monthly or weekly scales are more useful for water management. A method was
      proposed to downscale crop coefficient and water requirement from growing stage
      to substage scales, which is based on the interpolation of accumulated crop and
      reference evapotranspiration calculated from their values in growing stages. The
      proposed method was compared with two straightforward methods, that is, direct
      interpolation of crop evapotranspiration and crop coefficient by assuming that
      stage average values occurred in the middle of the stage. These methods were
      tested with a simulated daily crop evapotranspiration series. Results indicate
      that the proposed method is more reliable, showing that the downscaled crop
      evapotranspiration series is very close to the simulated ones.

PMID- 22619570
TI  - The nicotinic acetylcholine receptor as a target for antidepressant drug
      development.
AB  - An important new area of antidepressant drug development involves targeting the
      nicotinic acetylcholine receptor (nAChR). This receptor, which is distributed
      widely in regions of the brain associated with depression, is also implicated in
      other important processes that are relevant to depression, such as stress and
      inflammation. The two classes of drugs that target nAChRs can be broadly divided
      into mecamylamine- and cytisine-based compounds. These drugs probably exert their
      effects via antagonism at alpha4beta2 nAChRs, and strong preclinical data support
      the antidepressant efficacy of both classes when used in conjunction with other
      primary antidepressants (e.g., monoamine reuptake inhibitors). Although clinical
      data remain limited, preliminary results in this area constitute a compelling
      argument for further evaluation of the nAChR as a target for future
      antidepressant drug development.

PMID- 22619573
TI  - Comparative analysis of apoptotic resistance of mesenchymal stem cells isolated
      from human bone marrow and adipose tissue.
AB  - AIM: Mesenchymal stem cells (MSCs) isolated from human bone marrow (hBM) and
      adipose tissue (hAT) are perceived as attractive sources of stem cells for cell
      therapy. The aim of this study was to compare MSCs from hBM and hAT for their
      immunocytochemistry staining and resistance to in vitro apoptosis. METHODS: In
      our study, we investigated the antiapoptotic ability of these MSCs toward
      oxidative stress induced by hydrogen peroxide (H(2)O(2)) and serum deprivation.
      Results were assessed by MTT and flow cytometry. All experiments were repeated a
      minimum of three times. RESULTS: Flow cytometry and MTT analysis revealed that
      hAT-MSCs exhibited a higher resistance toward H(2)O(2)-induced apoptosis (n = 3,
      hBM-hAT viability H(2)O(2)  58.43 +/- 1.24-73.02 +/- 1.44, P < 0.02) and to serum
      deprivation-induced apoptosis at days 1 and 4 than the hBM-MSCs (n = 3, hAT-hBM
      absorbance, resp., day 1: 0.305 +/- 0.027-0.234 +/- 0.015, P = 0.029, day 4:
      0.355 +/- 0.003-0.318 +/- 0.007, P = 0.001, and day 7: 0.400 +/- 0.017-0.356 +/-
      0.008, P = 0.672). hAT-MSCs showed superior tolerance to oxidative stress
      triggered by 2 mmol/L H(2)O(2) and also have superior antiapoptosis capacity
      toward serum-free culture. CONCLUSION: In this study we found that hAT-MSCs are
      more resistant to in vitro apoptosis.

PMID- 22619574
TI  - Water hyacinth Eichhornia crassipes (Mart.) Solms-Laubach dynamics and succession
      in the Nyanza Gulf of Lake Victoria (east Africa): implications for water quality
      and biodiversity conservation.
AB  - This study, conducted in Nyanza Gulf of Lake Victoria, assessed ecological
      succession and dynamic status of water hyacinth. Results show that water hyacinth
      is the genesis of macrophyte succession. On establishment, water hyacinth mats
      are first invaded by native emergent macrophytes, Ipomoea aquatica Forsk., and
      Enydra fluctuans Lour., during early stages of succession. This is followed by
      hippo grass Vossia cuspidata (Roxb.) Griff. in mid- and late stages whose
      population peaks during climax stages of succession with concomitant decrease in
      water hyacinth biomass. Hippo grass depends on water hyacinth for buoyancy,
      anchorage, and nutrients. The study concludes that macrophyte succession alters
      aquatic biodiversity and that, since water hyacinth infestation and attendant
      succession are a symptom of broader watershed management and pollution problems,
      aquatic macrophyte control should include reduction of nutrient loads and
      implementing multifaceted approach that incorporates biological agents,
      mechanical/manual control with utilization of harvested weed for cottage industry
      by local communities.

PMID- 22619575
TI  - Lithium-acetate-mediated Biginelli one-pot multicomponent synthesis under solvent
      free conditions and cytotoxic activity against the human lung cancer cell line
      A549 and breast cancer cell line MCF7.
AB  - Various Biginelli compounds (dihydropyrimidinones) have been synthesized
      efficiently and in high yields under mild, solvent-free, and eco-friendly
      conditions in a one-pot reaction of 1,3-dicarbonyl compounds, aldehydes, and
      urea/thiourea/acetyl thiourea using lithium-acetate as a novel catalyst without
      the addition of any proton source. Comparative catalytic efficiency of lithium
      acetate and polyphosphoric acid to catalyze Biginelli condensation is also
      studied under neat conditions. The reaction is carried out in the absence of any
      solvent and represents an improvement of the classical Biginelli protocol and an
      advantage in comparison with FeCl(3).6H(2)O, NiCl(2).6H(2)O and CoCl(2).6H(2)O
      that were used with HCl as a cocatalyst. Compared to classical Biginelli reaction
      conditions, the present method has advantages of good yields, short reaction
      times, and experimental simplicity. The obtained products have been identified by
      spectral ((1)H NMR and IR) data and their melting points. The prepared compounds
      are evaluated for anticancer activity against two human cancer cell lines (lung
      cancer cell line A549 and breast cancer cell line MCF7).

PMID- 22619576
TI  - Effect of growth stage on the efficacy of postemergence herbicides on four weed
      species of direct-seeded rice.
AB  - The efficacy of bispyribac-sodium, fenoxaprop + ethoxysulfuron, and penoxsulam +
      cyhalofop was evaluated against barnyardgrass, Chinese sprangletop, junglerice,
      and southern crabgrass when applied at four-, six-, and eight-leaf stages. When
      applied at the four-leaf stage, bispyribac-sodium provided greater than 97%
      control of barnyardgrass, junglerice, and southern crabgrass; however, it was
      slightly weak (74% control) on Chinese sprangletop. Irrespective of the weed
      species, fenoxaprop + ethoxysulfuron provided greater than 97% control when
      applied at the four-leaf stage. At the same leaf stage, penoxsulam + cyhalofop
      controlled 89 to 100% barnyardgrass, Chinese sprangletop, and junglerice and only
      54% of southern crabgrass. The efficacy of herbicides was reduced when applied at
      the eight-leaf stage of the weeds; however, at this stage, fenoxaprop +
      ethoxysulfuron was effective in controlling 99% of Chinese sprangletop. The
      results demonstrate the importance of early herbicide application in controlling
      the weeds. The study identified that at the six-leaf stage of the weeds,
      fenoxaprop + ethoxysulfuron can effectively control Chinese sprangletop and
      southern crabgrass, penoxsulam + cyhalofop can effectively control Chinese
      sprangletop, and bispyribac-sodium can effectively control junglerice.

PMID- 22619578
TI  - Microbial contamination of date rutab collected from the markets of Al-Hofuf City
      in Saudi Arabia.
AB  - The microbial contamination of 60 samples from six date cultivars in the rutab
      stage purchased from different retail outlets in AL-Hofuf City, Saudi Arabia was
      studied. All samples were found contaminated with aerobic mesophilic bacteria at
      loads in the order 10(2) to 10(5) cfu/cm(2) with some significant differences
      among varieties that can be attributed to differences in the weather conditions
      during rutab season. Also all samples, except only one, were contaminated with
      molds and yeasts at loads in the order 10(2) to 10(3) cfu/cm(2). Potentially
      pathogenic Staphylococcus aureus was detected in 57 samples and A.
      flavus/parasiticus in 13 samples, while coliforms were detected in 39 samples.

PMID- 22619577
TI  - Comparison of three methods for the estimation of pineal gland volume using
      magnetic resonance imaging.
AB  - Pineal gland is a very important neuroendocrine organ with many physiological
      functions such as regulating circadian rhythm. Radiologically, the pineal gland
      volume is clinically important because it is usually difficult to distinguish
      small pineal tumors via magnetic resonance imaging (MRI). Although many studies
      have estimated the pineal gland volume using different techniques, to the best of
      our knowledge, there has so far been no stereological work done on this subject.
      The objective of the current paper was to determine the pineal gland volume using
      stereological methods and by the region of interest (ROI) on MRI. In this paper,
      the pineal gland volumes were calculated in a total of 62 subjects (36 females,
      26 males) who were free of any pineal lesions or tumors. The mean +/- SD pineal
      gland volumes of the point-counting, planimetry, and ROI groups were 99.55 +/-
      51.34, 102.69 +/- 40.39, and 104.33 +/- 40.45 mm(3), respectively. No significant
      difference was found among the methods of calculating pineal gland volume (P >
      0.05). From these results, it can be concluded that each technique is an
      unbiased, efficient, and reliable method, ideally suitable for in vivo
      examination of MRI data for pineal gland volume estimation.

PMID- 22619579
TI  - Genetic diversity and population differentiation of Guignardia mangiferae from
      "Tahiti" acid lime.
AB  - Among the citrus plants, "Tahiti" acid lime is known as a host of G. mangiferae
      fungi. This species is considered endophytic for citrus plants and is easily
      isolated from asymptomatic fruits and leaves. G. mangiferae is genetically
      related and sometimes confused with G. citricarpa which causes Citrus Black Spot
      (CBS). "Tahiti" acid lime is one of the few species that means to be resistant to
      this disease because it does not present symptoms. Despite the fact that it is
      commonly found in citric plants, little is known about the populations of G.
      mangiferae associated with these plants. Hence, the objective of this work was to
      gain insights about the genetic diversity of the G. mangiferae populations that
      colonize "Tahiti" acid limes by sequencing cistron ITS1-5.8S-ITS2. It was
      verified that "Tahiti" acid lime plants are hosts of G. mangiferae and also of G.
      citricarpa, without presenting symptoms of CBS. Populations of G. mangiferae
      present low-to-moderate genetic diversity and show little-to-moderate levels of
      population differentiation. As gene flow was detected among the studied
      populations and they share haplotypes, it is possible that all populations, from
      citrus plants and also from the other known hosts of this fungus, belong to one
      great panmictic population.

PMID- 22619580
TI  - Preparation and characterization of Ni-doped TiO2 materials for photocurrent and
      photocatalytic applications.
AB  - Different amounts of Ni-doped TiO(2) (Ni = 0.1 to 10%) powders and thin films
      were prepared by following a conventional coprecipitation and sol-gel dip coating
      techniques, respectively, at 400 to 800 degrees C, and were thoroughly
      characterized by means of XRD, FT-IR, FT-Raman, DRS, UV-visible, BET surface
      area, zeta potential, flat band potential, and photocurrent measurement
      techniques. Photocatalytic abilities of Ni-doped TiO(2) powders were evaluated by
      means of methylene blue (MB) degradation reaction under simulated solar light.
      Characterization results suggest that as a dopant, Ni stabilizes TiO(2) in the
      form of anatase phase, reduces its bandgap energy, and adjusts its flat band
      potentials such that this material can be employed for photoelectrochemical (PEC)
      oxidation of water reaction. The photocatalytic activity and photocurrent ability
      of TiO(2) have been enhanced by doping of Ni in TiO(2). The kinetic studies
      revealed that the MB degradation reaction follows the Langmuir-Hinshelwood first
      order reaction relationship.

PMID- 22619581
TI  - Effect of storage conditions and storage periods on seed germination in eleven
      populations of Swertia chirayita: a critically endangered medicinal herb in
      Himalaya.
AB  - Effect of different storage conditions (room temperature, 4 degrees C, and -15
      degrees C) and different storage periods over 24 months on seed germination in
      Swertia chirayita collected from different altitudes in Sikkim Himalaya was
      determined. Multivariate ANOVA revealed significant (P < 0.0001) effect of
      storage condition and storage period on seed germination and mean germination
      time. Seed germination percentage significantly (P < 0.01) varied between 87.78%
      (Sc5) and 100% (Sc2) during initial testing. Comparatively, high seed
      germination, low mean germination time, and low rate of fall in seed germination
      percentage in seeds stored at 4 degrees C over different storage period were
      recorded. In addition, above 50% seed germination in majority of the populations
      even after 24 months of storage suggests 4 degrees C as the most appropriate
      storage condition for long-term storage of seeds of S. chirayita.

PMID- 22619582
TI  - Immobilized horseradish peroxidase on discs of polyvinyl alcohol-glutaraldehyde
      coated with polyaniline.
AB  - Discs of network polyvinyl alcohol-glutaraldehyde (PVAG) were synthesized and
      coated with polyaniline (PANI) using glutaraldehyde as a chemical arm (PVAG-PANIG
      HRP disc). The best conditions for the immobilization were established as about
      1.0 mg mL(-1) of protein, for 60 min and pH 5.5. The soluble enzyme lost all of
      its activity after incubation at 70 degrees C for 15 min, whereas the PVAG-PANIG
      HRP disc retained about half of the initial activity for pyrogallol. The same
      PVAG-PANIG-HRP disc was used consecutively three times without any activity
      lossbut presented 25% of the initial activity after the 7th use. PVAG-PANIG-HRP
      disc retained approximately 80% and 60% of its initial activity after 60 and 80
      days of storage, respectively. Resorcinol, m-cresol, catechol, pyrogallol, alpha
      naphthol, betanaphthol, and 4, 4'-diaminodiphenyl benzidine were efficiently
      oxidized by the PVAG-PANIG-HRP disc (from about 70% to 90%), and it was less
      efficient towards aniline, phenol, and 2-nitrosonaphthol.

PMID- 22619583
TI  - Antibiotic resistant Salmonella and Vibrio associated with farmed Litopenaeus
      vannamei.
AB  - Salmonella and Vibrio species were isolated and identified from Litopenaeus
      vannamei cultured in shrimp farms. Shrimp samples showed occurrence of 3.3% of
      Salmonella and 48.3% of Vibrio. The isolates were also screened for antibiotic
      resistance to oxolinic acid, sulphonamides, tetracycline,
      sulfamethoxazole/trimethoprim, norfloxacin, ampicillin, doxycycline
      hydrochloride, erythromycin, chloramphenicol, and nitrofurantoin. Salmonella
      enterica serovar Corvallis isolated from shrimp showed individual and multiple
      antibiotic resistance patterns. Five Vibrio species having individual and
      multiple antibiotic resistance were also identified. They were Vibrio cholerae
      (18.3%), V. mimicus (16.7%), V. parahaemolyticus (10%), V. vulnificus (6.7%), and
      V. alginolyticus (1.7%). Farm owners should be concerned about the presence of
      these pathogenic bacteria which also contributes to human health risk and should
      adopt best management practices for responsible aquaculture to ensure the quality
      of shrimp.

PMID- 22619584
TI  - Comparing health-related quality of life of cancer patients under chemotherapy
      and of their caregivers.
AB  - INTRODUCTION: Cancer is a major disorder physically and psychologically affecting
      both patients and their caregivers. In this study, health-related quality of life
      (HRQoL) of patient-caregiver dyads during the period of chemotherapy was
      assessed. MATERIAL AND METHODS: Two hundred twenty-two cancer patient-caregiver
      dyads were enrolled in the study, which was conducted from October 2008 to March
      2009. HRQoL was evaluated with EQ-5D. RESULTS: The mean age of the sample was
      57.4 and 48.9 for patients and caregivers, respectively. The EQ-5D descriptive
      system indicates that female patients more frequently experience anxiety and
      depression than male patients. Male and higher-education caregivers had higher
      VAS scores, while demographic factors did not seem to influence patients' HRQoL.
      Anxiety and depression of caregivers were correlated with patients' problems in
      self-care and usual activities. CONCLUSIONS: Quality of life is highly influenced
      during the period of chemotherapy for both patients and caregivers and is often
      under reported. Interventions that can improve HRQoL, especially in the domain of
      mental health for both cancer patients and their caregivers, need to be
      implemented.

PMID- 22619585
TI  - Effects of exercise on oxidative stress in rats induced by ozone.
AB  - Oxidative stress (OS) induced by acute exercise is reduced by chronic exercise.
      Ozone (O(3)) exposure produces OS. The aim of this study was to determine if
      aerobic exercise (AE) reduced OS produced by O(3). A pilot experiment was
      performed with male Wistar rats submitted to AE (trained to swim 90 min/day).
      Adaptation to exercise was demonstrated three weeks after training by means of
      changes in reduced nitrates (NO(x)) in plasma. Therefore, two-week training was
      chosen for the following experiments. Six of twelve trained rats were exposed to
      O(3) (0.5 ppm, 4 h/day, one hour before exercise). Two groups of sedentary
      animals (n = 6 each) were used as controls, one of which was exposed to O(3). At
      the end of the experiments NO(x), 8-isoprostane (8-IP), malondialdehyde (MDA),
      superoxide dismutase (SOD) activity, and carbonyls (CBs) were measured in plasma.
      CBs did not change in any group. O(3)-induced OS was manifested by reduced NO(x)
      and SOD activity, as well as increased 8-IP and MDA. Exercise significantly
      blocked O(3) effects although SOD was also decreased by exercise (a greater drop
      occurring in the O(3) group). It is concluded that AE protects against OS
      produced by O(3) and the effect is independent of SOD.

PMID- 22619587
TI  - Determination of effective factors on power requirement and conveying capacity of
      a screw conveyor under three paddy grain varieties.
AB  - An experiment was conducted to investigate the effect of screw speed, inclination
      angle and variety on the required power, and conveying capacity of a screw
      conveyor. The experiment was designed with four levels of screw speed (600, 800,
      1000, and 1200 rpm), five levels of inclination angle (0, 20, 40, 60, and 80
      degrees ), and three levels of variety (Alikazemi, Hashemi, and Khazar). The
      Length, diameter, and pitch of screw were 2, 0.78, and 0.5 m, respectively. The
      experimental design was a randomized complete block (RCB) with factorial layout.
      Maximum and minimum power requirements of tested screw conveyor were 99.29 and
      81.16 Watt corresponding to conveying capacity of 3.210 and 1.975 ton/hour
      obtained for khazar and Alikazemi varieties, respectively. The results indicated
      that as screw inclination angle increased from 0 to 80 degrees , the conveying
      capacity decreased significantly from 3.581 to 0.932 t/h. It can be concluded
      that the most conveying capacity was 4.955 t/h at tests with khazar variety and
      conveyor inclination angle zero degree.

PMID- 22619586
TI  - Mitochondrial electron transport chain in heavy metal-induced neurotoxicity:
      effects of cadmium, mercury, and copper.
AB  - To clarify the role of mitochondrial electron transport chain (mtETC) in heavy
      metal-induced neurotoxicity, we studied action of Cd(2+), Hg(2+), and Cu(2+) on
      cell viability, intracellular reactive oxygen species formation, respiratory
      function, and mitochondrial membrane potential of rat cell line PC12. As found,
      the metals produced, although in a different way, dose- and time-dependent
      changes of all these parameters. Importantly, Cd(2+) beginning from 10 [mu]M and
      already at short incubation time (3 h) significantly inhibited the FCCP-uncoupled
      cell respiration; besides, practically the complete inhibition of the respiration
      was reached after 3 h incubation with 50 [mu]M Hg(2+) or 500 [mu]M Cd(2+),
      whereas even after 48 h exposure with 500 [mu]M Cu(2+), only a 50% inhibition of
      the respiration occurred. Against the Cd(2+)-induced cell injury, not only
      different antioxidants and mitochondrial permeability transition pore inhibitors
      were protective but also such mtETC effectors as FCCP and stigmatellin (complex
      III inhibitor). However, all mtETC effectors used did not protect against the
      Hg(2+)- or Cu(2+)-induced cell damage. Notably, stigmatellin was shown to be one
      of the strongest protectors against the Cd(2+)-induced cell damage, producing a
      15-20% increase in the cell viability. The mechanisms of the mtETC involvement in
      the heavy-metal-induced mitochondrial membrane permeabilization and cell death
      are discussed.

PMID- 22619588
TI  - Variation in nectar volume and sugar concentration of Allium ursinum L. ssp.
      ucrainicum in three habitats.
AB  - Floral nectar volume and concentration of ramson (Allium ursinum L. ssp.
      ucrainicum) were investigated in three different habitats, including two types of
      sessile oak-hornbeam association on brown forest soil with clay illuviation and a
      silver lime-flowering ash rock forest association on rendzina. Daily nectar
      production ranged from 0.1 to 3.8 MUL per flower with sugar concentrations of 25
      to 50%. Mean nectar volumes and concentrations showed significant differences
      between freely exposed flowers and covered flowers, which had been isolated from
      flower visitors 24 h prior to nectar studies. Both the amount and quality of
      nectar were affected by microclimatic conditions and soil properties and varied
      between populations at different habitats. In the silver lime-flowering ash rock
      forest association mean nectar volumes and concentrations were lower than in a
      typical sessile oak-hornbeam association on three occasions, the difference being
      significant in two cases. During full bloom, the date of sampling did not have a
      profound effect on either nectar volume or concentration.

PMID- 22619589
TI  - Combined contribution of endothelial relaxing autacoides in the rat femoral
      artery response to CPCA: an adenosine A2 receptor agonist.
AB  - We examined the contribution of endothelial relaxing factors and potassium
      channels in actions of CPCA, potent adenosine A(2) receptor agonist, on isolated
      intact male rat femoral artery (FA). CPCA produced concentration-dependent
      relaxation of FA, which was notably, but not completely, reduced after
      endothelial denudation. DPCPX, A(1) receptor antagonist, had no significant
      effect, while SCH 58261 (A(2A) receptor antagonist) notably reduced CPCA-evoked
      effect. Pharmacological inhibition of nitric oxide synthase or cyclooxygenase
      comparably reduced CPCA-evoked action, still in a lesser degree than after
      denudation. In the presence of buffer with high K(+) (100  mM), CPCA-produced
      relaxations were almost abolished. TEA (nonselective K(Ca) blocker),
      glibenclamide (K(ATP) blocker), Ba(++) (K(IR) blocker), or ouabain (Na(+)/K(+)
      ATPase inhibitor) did not change CPCA-induced relaxation. Concentration-response
      curve for CPCA was significantly shifted to the right after the incubation of
      apamin (SK channel blocker). CPCA produced concentration-dependent relaxation of
      FA that was partly dependent on endothelial cells. Endothelium-related portion of
      CPCA-elicited effect was mediated by combined action of endothelial NO,
      prostacyclin, and EDHF after activation of endothelial A(2A) receptors. Small
      conductance K(Ca) channels were involved in this action.

PMID- 22619590
TI  - Determination of iodate in food, environmental, and biological samples after
      solid-phase extraction with Ni-Al-Zr ternary layered double hydroxide as a
      nanosorbent.
AB  - Nanostructured nickel-aluminum-zirconium ternary layered double hydroxide was
      successfully applied as a solid-phase extraction sorbent for the separation and
      pre-concentration of trace levels of iodate in food, environmental and biological
      samples. An indirect method was used for monitoring of the extracted iodate ions.
      The method is based on the reaction of the iodate with iodide in acidic solution
      to produce iodine, which can be spectrophotometrically monitored at 352 nm. The
      absorbance is directly proportional to the concentration of iodate in the sample.
      The effect of several parameters such as pH, sample flow rate, amount of
      nanosorbent, elution conditions, sample volume, and coexisting ions on the
      recovery was investigated. In the optimum experimental conditions, the limit of
      detection (3s) and enrichment factor were 0.12 MUg mL(-1) and 20, respectively.
      The calibration graph using the preconcentration system was linear in the range
      of 0.2-2.8 MUg mL(-1) with a correlation coefficient of 0.998. In order to
      validate the presented method, a certified reference material, NIST SRM 1549, was
      also analyzed.

PMID- 22619591
TI  - Simple reversed-phase HPLC method with spectrophotometric detection for measuring
      acetaminophen-protein adducts in rat liver samples.
AB  - A simple reversed-phase HPLC method for measuring hepatic levels of acetaminophen
      (APAP-) protein adduct following an overdose of APAP was developed. An aliquot
      of liver homogenate in phosphate-buffered saline pH 7.4 (PBS) was placed on a
      Nanosep centrifugal device, which was centrifuged to obtain a protein residue.
      This residue was incubated with a solution of p-aminobenzoic acid (PABA), the
      internal standard, and bacterial protease in PBS, transferred to a Nanosep
      centrifugal device, and centrifuged. A 100 MUL portion of the filtrate was
      analyzed on a YMC-Pack ODS-AMQ C18 column, using 100 mM potassium dihydrogen
      phosphate-methanol-acetic acid (100 : 0.6 : 0.1) as the mobile phase, a flow rate
      of 1 mL/min, and photometric detection at 254 nm. PABA and APAP-cystein-S-yl
      (APAP-Cys) eluted at ~14.7 min and 22.7 min, respectively. Method linearity,
      based on on-column concentrations of APAP-Cys, was observed over the range 0.078
      40 MUg. Recoveries of APAP-Cys from spiked blank liver homogenates ranged from
      ~83% to 91%. Limits of detection and of quantification of APAP-Cys, based on
      column concentrations, were 0.06 MUg and 0.14 MUg, respectively. RSD values for
      interday and intraday analyses of a blank liver homogenate spiked with APAP-Cyst
      at three levels were, in all cases, <=1.0% and <1.5%, respectively. The proposed
      method was found appropriate for comparing the antidotal properties of N
      acetylcysteine and taurine in a rat model of APAP poisoning.

PMID- 22619592
TI  - Characterization of the immune response induced by a commercially available
      inactivated bluetongue virus serotype 1 vaccine in sheep.
AB  - The protective immune response generated by a commercial monovalent inactivated
      vaccine against bluetongue virus serotype 1 (BTV1) was studied. Five sheep were
      vaccinated, boost-vaccinated, and then challenged against BTV1 ALG/2006. RT-PCR
      did not detect viremia at any time during the experiment. Except a temperature
      increase observed after the initial and boost vaccinations, no clinical signs or
      lesions were observed. A specific and protective antibody response checked by
      ELISA was induced after vaccination and boost vaccination. This specific antibody
      response was associated with a significant increase in B lymphocytes confirmed by
      flow cytometry, while significant increases were not observed in T lymphocyte
      subpopulations (CD4(+), CD8(+), and WC1(+)), CD25(+) regulatory cells, or CD14(+)
      monocytes. After challenge with BTV1, the antibody response was much higher than
      during the boost vaccination period, and it was associated with a significant
      increase in B lymphocytes, CD14(+) monocytes, CD25(+) regulatory cells, and
      CD8(+) cytotoxic T lymphocytes.

PMID- 22619593
TI  - Social capital and technological literacy in Taiwan.
AB  - The burgeoning interest in social capital within the technology community
      represents a welcome move towards a concern for the social elements of
      technological adaptation and capacity. Since technology plays an ever larger role
      in our daily life, it is necessary to articulate social capital and its
      relationship to technological literacy. A nationwide data was collected by area
      sampling, and position generator was used to measure social capital. Regression
      model was constructed for technological literacy. Age, gender, education, income,
      web access, and social capital were included as independent variables. The
      results show that age, gender, education, web access, and social capital were
      good predictors of technological literacy. It is concluded that social capital is
      helpful in coping with rapid technological change. Theoretical and empirical
      implications and future research are discussed.

PMID- 22619594
TI  - Identification and characterization of differentially expressed transcripts in
      the gills of freshwater prawn (Macrobrachium rosenbergii) under salt stress.
AB  - The giant freshwater prawn, Macrobrachium rosenbergii, is an economically
      important species. It is a euryhaline shrimp, surviving in wide-range salinity
      conditions. A change in gene expression has been suggested as an important
      component for stress management. To better understand the osmoregulatory
      mechanisms mediated by the gill, a subtractive and suppressive hybridization
      (SSH) tool was used to identify expressed transcripts linked to adaptations in
      saline water. A total of 117 transcripts represented potentially expressed under
      salinity conditions. BLAST analysis identified 22% as known genes, 9% as
      uncharacterized showing homologous to unannotated ESTs, and 69% as unknown
      sequences. All the identified known genes representing broad spectrum of
      biological pathways were particularly linked to stress tolerance including
      salinity tolerance. Expression analysis of 10 known genes and 7
      unknown/uncharacterized genes suggested their upregulation in the gills of prawn
      exposed to saline water as compared to control indicating that these are likely
      to be associated with salinity acclimation. Rapid amplification of cDNA ends
      (RACE) was used for obtaining full-length cDNA of MRSW-40 clone that was highly
      upregulated during salt exposure. The sequenced ESTs presented here will have
      potential implications for future understanding about salinity acclimation and/or
      tolerance of the prawn.

PMID- 22619595
TI  - Defluorination of sodium fluoroacetate by bacteria from soil and plants in
      Brazil.
AB  - The aim of this work was to isolate and identify bacteria able to degrade sodium
      fluoroacetate from soil and plant samples collected in areas where the
      fluoroacetate-containing plants Mascagnia rigida and Palicourea aenofusca are
      found. The samples were cultivated in mineral medium added with 20 mmol L(-1)
      sodium fluoroacetate. Seven isolates were identified by 16S rRNA gene sequencing
      as Paenibacillus sp. (ECPB01), Burkholderia sp. (ECPB02), Cupriavidus sp.
      (ECPB03), Staphylococcus sp. (ECPB04), Ancylobacter sp. (ECPB05), Ralstonia sp.
      (ECPB06), and Stenotrophomonas sp. (ECPB07). All seven isolates degraded sodium
      fluoroacetate-containing in the medium, reaching defluorination rate of fluoride
      ion of 20 mmol L(-1). Six of them are reported for the first time as able to
      degrade sodium fluoroacetate (SF). In the future, some of these microorganisms
      can be used to establish in the rumen an engineered bacterial population able to
      degrade sodium fluoroacetate and protect ruminants from the poisoning by this
      compound.

PMID- 22619596
TI  - Hydrogen generation from Al-NiCl2/NaBH4 mixture affected by lanthanum metal.
AB  - The effect of La on Al/NaBH(4) hydrolysis was elaborated in the present paper.
      Hydrogen generation amount increases but hydrogen generation rate decreases with
      La content increasing. There is an optimized composition that Al-15 wt% La-5 wt%
      NiCl(2)/NaBH(4) mixture (Al-15 wt% La-5 wt% NiCl(2)/NaBH(4) weight ratio, 1 : 3)
      has 126 mL g(-1 )min(-1) maximum hydrogen generation rate and 1764 mL g(-1)
      hydrogen generation amount within 60 min. The efficiency is 88%. Combined with
      NiCl(2), La has great effect on NaBH(4) hydrolysis but has little effect on Al
      hydrolysis. Increasing La content is helpful to decrease the particle size of Al
      La-NiCl(2) in the milling process, which induces that the hydrolysis byproduct
      Ni(2)B is highly distributed into Al(OH)(3) and the catalytic reactivity of
      Ni(2)B/Al(OH)(3) is increased therefore. But hydrolysis byproduct La(OH)(3)
      deposits on Al surface and leads to some side effect. The Al-La-NiCl(2)/NaBH(4)
      mixture has good stability in low temperature and its hydrolytic performance can
      be improved with increasing global temperature. Therefore, the mixture has good
      safety and can be applied as on board hydrogen generation material.

PMID- 22619597
TI  - Micelle mediated trace level sulfide quantification through cloud point
      extraction.
AB  - A simple cloud point extraction protocol has been proposed for the quantification
      of sulfide at trace level. The method is based on the reduction of iron (III) to
      iron (II) by the sulfide and the subsequent complexation of metal ion with
      nitroso-R salt in alkaline medium. The resulting green-colored complex was
      extracted through cloud point formation using cationic surfactant, that is,
      cetylpyridinium chloride, and the obtained surfactant phase was homogenized by
      ethanol before its absorbance measurement at 710 nm. The reaction variables like
      metal ion, ligand, surfactant concentration, and medium pH on the cloud point
      extraction of the metal-ligand complex have been optimized. The interference
      effect of the common anions and cations was studied. The proposed method has been
      successfully applied to quantify the trace level sulfide in the leachate samples
      of the landfill and water samples from bore wells and ponds. The validity of the
      proposed method has been studied by spiking the samples with known quantities of
      sulfide as well as comparing with the results obtained by the standard method.

PMID- 22619598
TI  - Electrospinning synthesis and photocatalytic activity of mesoporous TiO2
      nanofibers.
AB  - Titanium dioxide (TiO(2)) nanofibers in the anatase structure were successfully
      prepared via electrospinning technique followed by calcination process. The
      morphologies, crystal structure, surface area, and the photocatalytic activity of
      resulting TiO(2) nanofibers were characterized by field emission scanning
      electron microscopy (FE-SEM), transmission electron microscopy (TEM), X-ray
      diffraction (XRD), nitrogen sorption, and UV-vis spectroscopy. The results
      revealed that calcination temperature had greatly influenced the morphologies of
      TiO(2) nanofibers, but no obvious effect was noticed on the crystal structure of
      TiO(2) nanofibers. The photocatalytic properties of TiO(2) nanofibers were
      evaluated by photocatalytic degradation of rhodamine B (RhB) in water under
      visible light irradiation. It was observed that TiO(2) nanofibers obtained by
      calcination at 500 degrees C for 3 hours exhibited the most excellent
      photocatalytic activity. We present a novel and simple method to fabricate TiO(2)
      nanofibers with high-photocatalytic activity.

PMID- 22619600
TI  - Pantoea agglomerans in immunodeficient patients with different respiratory
      symptoms.
AB  - The aim of this paper was to determine in 32 patients from 4 different Mexican
      hospitals the frequency of opportunistic bacteria in the 2010 to 2011 time
      period. The patients were divided in 4 groups. Group 1 included 21 HIV positive
      patients with acute respiratory syndrome. Four HIV positive patients with
      tuberculosis symptoms were included in Group 2; two patients with tuberculosis
      symptoms and one asymptomatic person formed Group 3. Reference Group 4 included 4
      patients from whom 4 strains of Mycobacterium spp. had been reported. The strains
      were isolated and identified by 16S rRNA gene amplification, API 20E and 50CH,
      biochemical test, and antibiotic sensitivity. The strains found were 10 Pantoea
      agglomerans, 6 Mycobacterium spp., 6 Pseudomonas spp. and 10 strains of normal
      floral species: Thermoactinomycetes bacterium (1), Enterococcus faecium (2),
      Bacillus licheniformis (1), Lactobacillus rhamnosus (2), Streptococcus oralis
      (2), Streptococcus anginosus (1), and Enterobacter hormaechei (1).

PMID- 22619599
TI  - Accuracy verification of magnetic resonance imaging (MRI) technology for lower
      limb prosthetic research: utilising animal soft tissue specimen and common socket
      casting materials.
AB  - Lower limb prosthetic socket shape and volume consistency can be quantified using
      MRI technology. Additionally, MRI images of the residual limb could be used as an
      input data for CAD-CAM technology and finite element studies. However, the
      accuracy of MRI when socket casting materials are used has to be defined. A
      number of six, 46 mm thick, cross-sections of an animal leg were used. Three
      specimens were wrapped with Plaster of Paris (POP) and the other three with
      commercially available silicone interface liner. Data was obtained by utilising
      MRI technology and then the segmented images compared to corresponding calliper
      measurement, photographic imaging, and water suspension techniques. The MRI
      measurement results were strongly correlated with actual diameter, surface area,
      and volume measurements. The results show that the selected scanning parameters
      and the semiautomatic segmentation method are adequate enough, considering the
      limit of clinical meaningful shape and volume fluctuation, for residual limb
      volume and the cross-sectional surface area measurements.

PMID- 22619601
TI  - The waveform fluctuation and the clinical factors of the initial and sustained
      erythropoietic response to continuous erythropoietin receptor activator in
      hemodialysis patients.
AB  - OBJECTIVES: Erythropoiesis-stimulating agents (ESA) are the main treatment for
      anemia in hemodialysis (HD) patients. We evaluated factors determining the
      response after treatment of a new ESA (continuous erythropoietin erythropoietin
      receptor activator (CERA)). METHODS: 61 HD patients were classified by their
      response at two different timings. First, patients whose hematocrit (Hct)
      increased 1.5% in the first week were defined as initial responders (IR, n = 16).
      We compared several parameters between IR and the rest of the study subjects (non
      IR, n = 45). Second, patients whose Hct increased 2% in the 4th week were defined
      as sustained responders (SR, n = 12), and we did a similar comparison. RESULTS:
      The Hct showed a waveform fluctuation. Compared with the rest, IR had
      significantly lower platelet counts and higher levels of ferritin, total protein,
      total bilirubin, and serum sodium, while SR had significantly lower levels of C
      reactive protein and low-density lipoprotein (All P < 0.05). In comparison with
      the rest, higher Hct persisted for 10 weeks in SR but only for two separate weeks
      (the 1st and 7th week) in IR. CONCLUSIONS: The initial and sustained
      erythropoietic responses are independent from each other and are associated with
      different factors. Treatment focusing on these factors may improve the response.

PMID- 22619602
TI  - Development and validation of quantitative structure-activity relationship models
      for compounds acting on serotoninergic receptors.
AB  - A quantitative structure-activity relationship (QSAR) study has been made on 20
      compounds with serotonin (5-HT) receptor affinity. Thin-layer chromatographic
      (TLC) data and physicochemical parameters were applied in this study. RP2 TLC
      60F(254) plates (silanized) impregnated with solutions of propionic acid,
      ethylbenzene, 4-ethylphenol, and propionamide (used as analogues of the key
      receptor amino acids) and their mixtures (denoted as S1-S7 biochromatographic
      models) were used in two developing phases as a model of drug-5-HT receptor
      interaction. The semiempirical method AM1 (HyperChem v. 7.0 program) and ACD/Labs
      v. 8.0 program were employed to calculate a set of physicochemical parameters for
      the investigated compounds. Correlation and multiple linear regression analysis
      were used to search for the best QSAR equations. The correlations obtained for
      the compounds studied represent their interactions with the proposed
      biochromatographic models. The good multivariate relationships (R(2) = 0.78-0.84)
      obtained by means of regression analysis can be used for predicting the
      quantitative effect of biological activity of different compounds with 5-HT
      receptor affinity. "Leave-one-out" (LOO) and "leave-N-out" (LNO) cross-validation
      methods were used to judge the predictive power of final regression equations.

PMID- 22619603
TI  - In vitro synergistic effect of Psidium guineense (Swartz) in combination with
      antimicrobial agents against methicillin-resistant Staphylococcus aureus strains.
AB  - The aim of this study was to evaluate the antimicrobial activity of aqueous
      extract of Psidium guineense Swartz (Araca-do-campo) and five antimicrobials
      (ampicillin, amoxicillin/clavulanic acid, cefoxitin, ciprofloxacin, and
      meropenem) against twelve strains of Staphylococcus aureus with a resistant
      phenotype previously determined by the disk diffusion method. Four S. aureus
      strains showed resistance to all antimicrobial agents tested and were selected
      for the study of the interaction between aqueous extract of P. guineense and
      antimicrobial agents, by the checkerboard method. The criteria used to evaluate
      the synergistic activity were defined by the fractional inhibitory concentration
      index (FICI). All S. aureus strains were susceptible to P. guineense as
      determined by the microdilution method. The combination of the P. guineense
      extract with the antimicrobial agents resulted in an eight-fold reduction in the
      MIC of these agents, which showed a FICI ranging from 0.125 to 0.5, suggesting a
      synergistic interaction against methicillin-resistant Staphylococcus aureus
      (MRSA) strains. The combination of the aqueous extract of P. guineense with
      cefoxitin showed the lowest FICI values. This study demonstrated that the aqueous
      extract of P. guineense combined with beta lactamics antimicrobials,
      fluoroquinolones, and carbapenems, acts synergistically by inhibiting MRSA
      strains.

PMID- 22619604
TI  - A study on L-asparaginase of Nocardia levis MK-VL_113.
AB  - An enzyme-based drug, L-asparaginase, was produced by Nocardia levis MK-VL_113
      isolated from laterite soils of Guntur region. Cultural parameters affecting the
      production of L-asparaginase by the strain were optimized. Maximal yields of L
      asparaginase were recorded from 3-day-old culture grown in modified asparagine
      glycerol salts broth with initial pH 7.0 at temperature 30 degrees C. Glycerol
      (2%) and yeast extract (1.5%) served as good carbon and nitrogen sources for L
      asparaginase production, respectively. Cell-disrupting agents like EDTA slightly
      enhanced the productivity of L-asparaginase. Ours is the first paper on the
      production of L-asparaginase by N. levis.

PMID- 22619605
TI  - Treatment of horizontal canal benign paroxysmal positional vertigo: a new
      rehabilitation technique.
AB  - The aim of this study was to evaluate the effectiveness of a new technical
      variant applied to the Gufoni's manoeuvre, in the treatment of horizontal canal
      benign paroxysmal positional vertigo (HSC-BPPV). 87 patients with BPPV of HSC (55
      women and 32 men), aged between 21 and 80 years, were randomized either to
      modified Gufoni's manoeuvre or to the Gufoni's manoeuvre. 93% of patients treated
      with modified Gufoni's manoeuvre was cured after the first treatment session, of
      which only 2% had a conversion into PSC-BPPV, while the Gufoni's manoeuvre led to
      a symptoms resolution in 88% of cases, of which 16% had a conversion into PSC
      BPPV. Therefore, the modified Gufoni's manoeuvre shows the same effectiveness in
      the resolution of symptoms of Gufoni's manoeuvre, but it appears more effective
      than the latter to reduce the percentage of conversion of the HSC-BPPV into PSC
      BPPV (chi(2) = 6.13, P = 0.047).

PMID- 22619606
TI  - The pyrolytic profile of lyophilized and deep-frozen compact part of the human
      bone.
AB  - Background. Bone grafts are used in the treatment of nonunion of fractures, bone
      tumors and in arthroplasty. Tissues preserved by lyophilization or deep freezing
      are used as implants nowadays. Lyophilized grafts are utilized in the therapy of
      birth defects and bone benign tumors, while deep-frozen ones are applied in
      orthopedics. The aim of the study was to compare the pyrolytic pattern, as an
      indirect means of the analysis of organic composition of deep-frozen and
      lyophilized compact part of the human bone. Methods. Samples of preserved bone
      tissue were subjected to thermolysis and tetrahydroammonium-hydroxide- (TMAH-)
      associated thermochemolysis coupled with gas chromatography and mass spectrometry
      (Py-GC/MS). Results. Derivatives of benzene, pyridine, pyrrole, phenol, sulfur
      compounds, nitriles, saturated and unsaturated aliphatic hydrocarbons, and fatty
      acids (C12-C20) were identified in the pyrolytic pattern. The pyrolyzates were
      the most abundant in derivatives of pyrrole and nitriles originated from
      proteins. The predominant product in pyrolytic pattern of the investigated bone
      was pyrrolo[1,2-alpha]piperazine-3,6-dione derived from collagen. The content of
      this compound significantly differentiated the lyophilized graft from the deep
      frozen one. Oleic and palmitic acid were predominant among fatty acids of the
      investigated samples. The deep-frozen implants were characterized by higher
      percentage of long-chain fatty acids than lyophilized grafts.

PMID- 22619607
TI  - Diet composition and feeding strategies of the stone marten (Martes foina) in a
      typical Mediterranean ecosystem.
AB  - Stone martens (Martes foina) are documented as generalist throughout their
      distributional range whose diet composition is affected by food availability. We
      tested if this occurs and what feeding strategies it follows in a typical
      Mediterranean ecosystem in Central Greece by analysing contents from 106
      stomachs, seasonally collected from three different habitats during 2003-2006.
      Seasonal variation in diet and feeding strategies was evident and linked to
      seasonal nutritional requirements, but possibly imposed by strong interference
      competition and intraguild predation. Fleshy fruits and arthropods predominated
      in the diet, but also mammals and birds were frequently consumed. An overall low
      dietary niche breadth (B(A) = 0.128) indicated a fruit specialization tendency. A
      generalised diet occurred in spring with high individual specialisation, whereas
      more animal-type prey was consumed than fruits. A population specialization
      towards fruits was indicated during summer and autumn, whereas insects were
      consumed occasionally by males. In those seasons it switched to more clumped food
      types such as fruits and insects. In winter it selectively exploited both adult
      and larvae insects and partially fruits overwinter on plants. The tendency to
      consume particular prey items seasonally reflected both the population specialist
      behaviour and the individual flexibility preyed on different food resources.

PMID- 22619608
TI  - Amazon rainforest exchange of carbon and subcanopy air flow: Manaus LBA site--a
      complex terrain condition.
AB  - On the moderately complex terrain covered by dense tropical Amazon Rainforest
      (Reserva Biologica do Cuieiras--ZF2--02 degrees 36'17.1'' S, 60 degrees 12'24.4''
      W), subcanopy horizontal and vertical gradients of the air temperature, CO(2)
      concentration and wind field were measured for the dry and wet periods in 2006.
      We tested the hypothesis that horizontal drainage flow over this study area is
      significant and can affect the interpretation of the high carbon uptake rates
      reported by previous works at this site. A similar experimental design as the one
      by Tota et al. (2008) was used with a network of wind, air temperature, and CO(2)
      sensors above and below the forest canopy. A persistent and systematic subcanopy
      nighttime upslope (positive buoyancy) and daytime downslope (negative buoyancy)
      flow pattern on a moderately inclined slope (12%) was observed. The
      microcirculations observed above the canopy (38 m) over the sloping area during
      nighttime presents a downward motion indicating vertical convergence and
      correspondent horizontal divergence toward the valley area. During the daytime an
      inverse pattern was observed. The micro-circulations above the canopy were driven
      mainly by buoyancy balancing the pressure gradient forces. In the subcanopy space
      the microcirculations were also driven by the same physical mechanisms but
      probably with the stress forcing contribution. The results also indicated that
      the horizontal and vertical scalar gradients (e.g., CO(2)) were modulated by
      these micro-circulations above and below the canopy, suggesting that estimates of
      advection using previous experimental approaches are not appropriate due to the
      tridimensional nature of the vertical and horizontal transport locally. This work
      also indicates that carbon budget from tower-based measurement is not enough to
      close the system, and one needs to include horizontal and vertical advection
      transport of CO(2) into those estimates.

PMID- 22619609
TI  - Evaluation of six patients with pulmonary carcinosarcoma with a literature
      review.
AB  - BACKGROUND: Carcinosarcoma of the lung is a rare malignant neoplasm. We evaluated
      the diagnosis and treatment of six carcinosarcoma cases, including a synchronous
      tumour and a solitary pulmonary tumour, along with the clinical and histological
      features and survival times. METHODS: From a retrospective analysis of 1076 non
      small-cell lung cancer resections performed between January 1996 and January
      2011, six patients (0.5%) with pulmonary carcinosarcoma (all males; mean age 58
      years; range 53-66) who underwent surgical treatment were studied. RESULTS: The
      mean tumour pathological T diameter was 7.2 cm (median 6 cm, range 3-14.5 cm).
      Only one patient was diagnosed with carcinosarcoma preoperatively. The clinical
      presentation and tumour localisations differed. The operations performed were a
      lobectomy (n = 4), pneumonectomy (n = 1), and bilobectomy (n = 1).
      Histologically, the epithelial characteristics of the tumours were consistent
      with squamous cell carcinoma in most of the patients. A complete resection was
      performed in all six patients. No mortality occurred in the early postoperative
      period. The median survival time was 9 (3-25) months. CONCLUSION: The
      preoperative diagnosis of carcinosarcoma of the lung is difficult due to the
      composition of the different histopathological structures. Complete surgical
      resection is the treatment of choice for pulmonary carcinosarcoma, although
      further studies are needed.

PMID- 22619610
TI  - Critical comparison between modified Monier-Williams and electrochemical methods
      to determine sulfite in aqueous solutions.
AB  - In the present work, known concentration of sulfite aqueous solutions in the
      presence and absence of gallic acid was measured to corroborate the validity of
      modified Monier-Williams method. Free and bound-sulfite was estimated by
      differential pulse voltammetry. To our surprise, the modified Monier-Williams
      method (also known as aspiration method) showed to be very inaccurate for free
      sulfite, although suitable for bound-sulfite determination. The differential
      pulse approach, using the standard addition method and a correction coefficient,
      proved to be swift, cheap, and very precise and accurate.

PMID- 22619611
TI  - Tuberculous meningitis in adults: a review of 160 cases.
AB  - OBJECTIVE: This study aimed to evaluate epidemiological, clinical, laboratory,
      and neuroimaging features of 160 adult patients with tuberculous meningitis (TBM)
      according to "Thwaites' diagnostic index." METHODS: The subjects of this
      retrospective study are the patients with TBM who were followed up between years
      1998 and 2009 in a tertiary referral hospital. Diagnosis of TBM was based on
      clinical, laboratory, and neuroimaging signs and Thwaites' diagnostic index.
      RESULTS: Mycobacterium tuberculosis was isolated from CSF in 59 of 148 patients.
      Seventeen percent of the patients died, 71% recovered completely, and 13%
      recovered with neurological sequel at the end of the sixth month. CONCLUSIONS:
      Despite new developments in laboratory or neuroimaging techniques, the diagnosis
      of TBM is still based on clinical features with the help of laboratory. Early
      diagnosis by suspecting TBM may prevent therapy delay and may result in decrease
      in the mortality and morbidity.

PMID- 22619612
TI  - Clinical characteristics of spinal levobupivacaine: hyperbaric compared with
      isobaric solution.
AB  - We performed a prospective, double-blinded study in 20 patients undergoing
      gynecologic surgery with lower abdominal incision, to investigate characteristics
      of intrathecal hyperbaric levobupivacaine compared with isobaric levobupivacaine.
      We randomly assigned them to receive 3 mL of either isobaric or hyperbaric 0.42%
      levobupivacaine intrathecally. We found that hyperbaric levobupivacaine, compared
      with isobaric levobupivacaine, spread faster to T10 level (2.8 +/- 1.1 versus 6.6
      +/- 4.7 minutes, P = 0.039), reached higher sensory block levels at 5 and 15
      minutes after injection (T8 versus L1, P = 0.011, and T4 versus T7, P = 0.027,
      resp.), and had a higher peak level (T4 versus T8, P = 0.040). Isobaric
      levobupivacaine caused a wider range of peak levels (L1 to C8) compared with
      hyperbaric form (T7 to T2). The level of T4 or higher reached 90% in the
      hyperbaric group compared with 20% in the isobaric group (P = 0.005). Our results
      suggest that hyperbaric levobupivacaine was more predictable for sensory block
      level and more effective for surgical procedures with lower abdominal approach.
      Hyperbaric levobupivacaine seems to be suitable, but the optimal dosage needs
      further investigation.

PMID- 22619613
TI  - Quantitative analysis of driving factors of grassland degradation: a case study
      in Xilin River Basin, Inner Mongolia.
AB  - Current literature suggests that grassland degradation occurs in areas with poor
      soil conditions or noticeable environmental changes and is often a result of
      overgrazing or human disturbances. However, these views are questioned in our
      analyses. Based on the analysis of satellite vegetation maps from 1984, 1998, and
      2004 for the Xilin River Basin, Inner Mongolia, China, and binary logistic
      regression (BLR) analysis, we observe the following: (1) grassland degradation is
      positively correlated with the growth density of climax communities; (2) our
      findings do not support a common notion that a decrease of biological
      productivity is a direct indicator of grassland degradation; (3) a causal
      relationship between grazing intensity and grassland degradation was not found;
      (4) degradation severity increased steadily towards roads but showed different
      trends near human settlements. This study found complex relationships between
      vegetation degradation and various microhabitat conditions, for example,
      elevation, slope, aspect, and proximity to water.

PMID- 22619614
TI  - Impact of the Project P.A.T.H.S. in the junior secondary school years: objective
      outcome evaluation based on eight waves of longitudinal data.
AB  - To assess the effectiveness of the Tier 1 Program of the Project P.A.T.H.S., a
      randomized group trial with eight waves of data collected was carried out. At the
      fifth year of data collection, 19 experimental schools (n = 2, 662 students) and
      24 control schools (n = 3, 272 students) participated in the study. Analyses
      based on individual growth curve modeling showed that participants in the
      experimental schools displayed better positive youth development than did
      participants in the control schools in terms of different indicators derived from
      the Chinese Positive Youth Development Scale, including moral competence and
      behavioral competence and cognitive behavioral competencies. Significant results
      were also found when examining the trajectories of psychological development
      among control and experimental participants who perceived the program to be
      beneficial. Findings based on longitudinal objective outcome evaluation strongly
      suggest that the Project P.A.T.H.S. is effective in promoting positive
      development in Hong Kong secondary school students.

PMID- 22619615
TI  - Spontaneous hybridization between Pinus mugo and Pinus sylvestris at the
      Lithuanian seaside: a morphological survey.
AB  - We address the problem of spontaneous hybridization between an exotic species
      Pinus mugo and the native/local P. sylvestris at the seaside spit of Kursiu
      Nerija in Lithuania. The objective was to identify spontaneous hybrids between P.
      mugo and P. sylvestris based on morphology traits among the individuals naturally
      regenerating at the seaside spit. The field inventory was carried out over the
      entire Lithuanian part of the spit, and 200 individuals morphologically
      intermediate between P. sylvestris and P. mugo were identified. Based on a
      weighted trait index, the intermediate individuals were grouped into two groups,
      one morphologically close to P. sylvestris and another close to P. mugo. The
      needle micromorphological traits of the putative hybrids were of intermediate
      values between P. mugo and P. sylvestris. The results provide a strong evidence
      of spontaneous hybridization between P. mugo and P. sylvestris in Lithuanian
      seaside spit of Kursiu Nerija.

PMID- 22619616
TI  - The effects of different insufflation pressures on liver functions assessed with
      LiMON on patients undergoing laparoscopic cholecystectomy.
AB  - PURPOSE: Laparoscopic cholecystectomy has been accepted as an alternative to
      laparotomy, but there is still controversy regarding the effects of
      pneumoperitoneum on splanchnic and hepatic perfusion. We assessed the effects of
      different insufflation pressures on liver functions by using indocyanine green
      elimination tests (ICG-PDR). METHODS: We analyzed 43 patients who were scheduled
      for laparoscopic cholecystectomy. The patients were randomly allocated to two
      groups. In Group I, the operation was performed using 10 mmHg pressure
      pneumoperitoneum. In Group II, 14 mmHg pressure pneumoperitoneum was used. The
      ICG-PDR measurements were made after induction (ICG-PDR 1) and after the end of
      the operation (ICG-PDR 2). Serum aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), and total bilirubin levels were all recorded
      preoperatively, 1 hour, and postoperative 24 hours after surgery. RESULTS: The
      ICG-PDR 1 values for Groups I and II were as follows: 26.78 +/- 4.2% per min
      versus 26.01 +/- 2.4% per min (P > 0.05). ICG-PDR 2 values were found to be 25.63
      +/- 2.1% per min in Group I versus 19.06 +/- 2.2% per min in Group II (P < 0.05).
      There was a statistically significant decrease between baseline and postoperative
      ICG-PDR values in Group II compared to Group I (P < 0.05). Statistically, there
      was an increase between baseline and postoperative 1st-hour serum AST and ALT
      level in Group II (P < 0.05) compared to Group I. No statistical differences were
      detected on postoperative 24st-hour serum AST and ALT levels and all the time
      bilirubin between groups (P > 0.05). CONCLUSION: In conclusion, the results show
      that 14 mmHg pressure pneumoperitoneum decreased the blood flow to the liver and
      increased postoperative 1st-hour serum AST and ALT levels. We think that 10 mmHg
      pressure pneumoperitoneum is superior to 14 mmHg pressure pneumoperitoneum in
      laparoscopic cholecystectomy.

PMID- 22619617
TI  - Cytotoxic, virucidal, and antiviral activity of South American plant and algae
      extracts.
AB  - Herpes simplex virus type 1 (HSV-1) infection has a prevalence of 70% in the
      human population. Treatment is based on acyclovir, valacyclovir, and foscarnet,
      three drugs that share the same mechanism of action and of which resistant
      strains have been isolated from patients. In this aspect, innovative drug
      therapies are required. Natural products offer unlimited opportunities for the
      discovery of antiviral compounds. In this study, 28 extracts corresponding to 24
      plant species and 4 alga species were assayed in vitro to detect antiviral
      activity against HSV-1. Six of the methanolic extracts inactivated viral
      particles by direct interaction and 14 presented antiviral activity when
      incubated with cells already infected. Most interesting antiviral activity values
      obtained are those of Limonium brasiliense, Psidium guajava, and Phyllanthus
      niruri, which inhibit HSV-1 replication in vitro with 50% effective concentration
      (EC(50)) values of 185, 118, and 60 MUg/mL, respectively. For these extracts
      toxicity values were calculated and therefore selectivity indexes (SI) obtained.
      Further characterization of the bioactive components of antiviral plants will
      pave the way for the discovery of new compounds against HSV-1.

PMID- 22619618
TI  - Progress towards mechanism-based treatment for Diamond-Blackfan anemia.
AB  - Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplastic anemia,
      characterized by macrocytic anemia, reticulocytopenia, and severely reduced
      numbers of erythroid precursors in the bone marrow. For more than fifty years,
      glucocorticoids have remained the main option for pharmacological treatment of
      DBA. While continuous glucocorticoid administration increases hemoglobin levels
      in a majority of DBA patients, it also causes severe side effects. There is
      therefore a great need for more specific and effective treatments to boost or
      replace the use of glucocorticoids. Over the years, many alternative therapies
      have been tried out, but most of them have shown to be ineffective. Here we
      review previous and current attempts to develop such alternative therapies for
      DBA. We further discuss how emerging knowledge regarding the pathological
      mechanism in DBA and the therapeutic mechanism of glucocorticoids treatment may
      reveal novel drug targets for DBA treatment.

PMID- 22619619
TI  - The effect of admission creatinine levels on one-year mortality in acute
      myocardial infarction.
AB  - BACKGROUND: We have known that patients with renal insufficiency (creatinine
      level) have increased mortality for coronary artery disease. In this study, the
      relationship between admission creatinine level and one year mortality are
      evaluated in patients with acute myocardial infarction (AMI). METHOD: 160 AMI
      patients (127 men and 33 women with a mean age of 59 +/- 13) were enrolled in the
      study. Serum creatinine levels were measured within 12 hours of AMI. The patients
      were divided into two groups according to admission serum creatinine level. (1)
      elevated group (serum creatinine > 1.3 mg/dL) and (2) normal group (<=1.3 mg/dL).
      One year mortality rates were evaluated. RESULTS: Elevated serum creatinine is
      observed in the 27 patients (16.9%). The mean creatinine level is 1.78 +/- 7
      mg/dL in the elevated group and 0.9 +/- 0.18 mg/dL in the normal group (P <
      0.0001). The mortality rate of the elevated group (n = 7, 25.9%) is higher than
      that of the normal group (n = 9, 6.8%). A significant increase in one year
      mortality is also observed (P=002) 60. CONCLUSION: The mildly elevated admission
      serum creatinine levels are markedly increased to one year mortality in patients
      with AMI.

PMID- 22619621
TI  - The phenox clot retriever as part of a multimodal mechanical thrombectomy
      approach in acute ischemic stroke: single center experience in 56 patients.
AB  - Purpose. We analyzed our experience with the phenox clot retriever as part of a
      multimodal mechanical thrombectomy (MTE) approach in acute ischemic stroke.
      Methods. 56 patients were treated by MTE with the phenox clot retriever alone or
      in combination with other modalities. Results. Overall we achieved TICI 2b/3
      reperfusion rates of 61,9%. In multimodally treated patients we achieved
      reperfusion rates of 72,8%. There were 3 (5,5%) severe adverse events, all
      symptomatic intracranial hemorrhages. The mean angio to reperfusion times (ART)
      were 74 minutes for phenox-only procedures and 51 minutes for multimodal
      procedures. A chronological analysis showed a reduction of ART from 70,5 to 49,4
      minutes and an increase of TICI 2b/3 recanalizations from 53,8% to 81,8%.
      Throughout the observation period there was a significant shift towards
      multimodal procedures with simultaneous increase of TICI 2b/3 reperfusions. Both
      effects are partially attributable to our institutional learning curve. NIHSS
      improvement could be seen in 54% (n = 28) overall and in 73% (n = 15) of MCA
      recanalizations. Conclusions. The phenox clot retriever is a safe and effective
      tool for MTE in acute stroke patients, with faster and better reperfusion results
      when used as part of a multimodal strategy. Clinical improvement is more frequent
      in MCA recanalizations.

PMID- 22619620
TI  - Angiotensins inhibit cell growth in GH3 lactosomatotroph pituitary tumor cell
      culture: a possible involvement of the p44/42 and p38 MAPK pathways.
AB  - The local renin-angiotensin system is present in the pituitary. We investigated
      the effects of angiotensins on GH3 lactosomatotroph cells proliferation in vitro
      and the involvement of p44/42 and p38 MAPK inhibitors in the growth-regulatory
      effects of angiotensins. Materials and Methods. Cell viability using the Mosmann
      method and proliferation by the measurement of BrdU incorporation during DNA
      synthesis were estimated. Results. Ang II and ang IV decreased the viability and
      proliferation of GH3 cells. Inhibitor of p44/42 MAPK attenuated the effects of
      ang II on cell viability and proliferation but did not affect the ang 5-8
      dependent actions. Inhibitor of p38 MAPK prevented the decrease in the number of
      GH3 cells in ang-II- and ang-IV-treated groups. Conclusions. The growth
      inhibitory effect of ang II is possibly mediated by the p44/42 MAPK. The p38 MAPK
      appears to mediate the inhibitory effects of both ang II and ang 5-8 upon cell
      survival.

PMID- 22619622
TI  - Fast hearing-threshold estimation using multiple auditory steady-state responses
      with narrow-band chirps and adaptive stimulus patterns.
AB  - This paper describes the estimation of hearing thresholds in normal-hearing and
      hearing-impaired subjects on the basis of multiple-frequency auditory steady
      state responses (ASSRs). The ASSR was measured using two new techniques: (i)
      adaptive stimulus patterns and (ii) narrow-band chirp stimuli. ASSR thresholds in
      16 normal-hearing and 16 hearing-impaired adults were obtained simultaneously at
      both ears at 500, 1000, 2000, and 4000 Hz, using a multiple-frequency stimulus
      built up of four one-octave-wide narrow-band chirps with a repetition rate of 40
      Hz. A statistical test in the frequency domain was used to detect the response.
      The recording of the steady-state responses was controlled in eight independent
      recording channels with an adaptive, semiautomatic algorithm. The average
      differences between the behavioural hearing thresholds and the ASSR threshold
      estimate were 10, 8, 13, and 15 dB for test frequencies of 500, 1000, 2000, and
      4000 Hz, respectively. The average overall test duration of 18.6 minutes for the
      threshold estimations at the four frequencies and both ears demonstrates the
      benefit of an adaptive recording algorithm and the efficiency of optimised narrow
      band chirp stimuli.

PMID- 22619623
TI  - The c.1460C>T polymorphism of MAO-A is associated with the risk of depression in
      postmenopausal women.
AB  - OBJECTIVE: The aim of the study was an evaluation of possible relationships
      between polymorphisms of serotoninergic system genes and the risk of depression
      in postmenopausal women. METHODS: We studied 332 women admitted to our department
      because of climacteric symptoms. The study group included 113 women with a
      diagnosis of depressive disorder according to the Hamilton rating scale for
      depression; the controls consisted of 219 women without depression. Serum 17beta
      estradiol concentrations were evaluated using radioimmunoassay, while
      polymorphisms in serotoninergic system genes: serotonin receptors 2A (HTR2A), 1B
      (HTR1B), and 2C (HTR2C); tryptophan hydroxylase 1 (TPH1) and 2 (TPH2), and
      monoamine oxidase A (MAO-A) were evaluated using polymerase chain reaction
      restriction. RESULTS: We found that the 1460T allele of MAO-A c.1460C>T (SNP
      1137070) appeared with a significantly higher frequency in depressed female
      patients than in the control group (P = 0.011) and the combined c.1460CT + TT
      genotypes were associated with a higher risk of depression (P = 0.0198). Patients
      with the 1460TT genotype had a significantly higher 17beta-estradiol
      concentration than patients with the 1460CT genotype (P = 0.0065) and 1460CC
      genotype (P = 0.0018). CONCLUSIONS: We concluded that depression in
      postmenopausal women is closely related to the genetic contribution of MAO-A.

PMID- 22619625
TI  - High prevalence of Candida yeast in milk samples from cows suffering from
      mastitis in poland.
AB  - Mastitis is an economically important disease in which fungi belonging to the
      genus Candida may participate as etiological agents. This study focused on
      determining the frequency of fungal isolation and differentiation of fungal
      species isolated from milk of mastitic cows. Sixty-six milk samples from mastitic
      cows were studied, and 55 strains of fungi were isolated. Seven different species
      classified as Candida were identified basing on phenotypic properties, and the
      dominating species was C. parapsilosis. Genomic DNA was isolated and amplified in
      PCR with ITS1 and NL2 primers. Amplification products were digested with
      restriction enzymes HpaII and EcoRI. Amplification of DNA with ITS1 and NL2
      primers resulted in products of different sizes. Comparison of product sizes in
      restriction fragment PCR REA confirmed differences among species. Strains grouped
      together on the basis of phenotype characteristics differed in restriction
      fragment profiles. None of the investigated species showed similar genetic
      profiles.

PMID- 22619624
TI  - An overview on dry eye treatment: approaches for cyclosporin a delivery.
AB  - Dry eye syndrome (DES, Keratoconjunctivitis sicca) is a common disorder of the
      tear film caused by decreased tear production or increased evaporation. Changes
      in tear composition also promote inflammation on the ocular surface by various
      mechanisms. Artificial tear drops, tear retention treatment, stimulation of tear
      secretion, or anti-inflammatory drugs may be used for dry eye treatment according
      to the severity of the disease. For untreated patients, the risk of ocular
      infection increases at considerable level and clinical course of the disease may
      proceed up to infection, corneal ulcer, and blindness. Artificial tears and/or
      punctual occlusions are used for tear replacement or preservation. New treatment
      approaches are designed to modify the underlying disease process. For the
      treatment of severe dry eye disease, cyclosporin A (CsA), the first one of the
      new generation immunomodulatory drugs, which has an anti-inflammatory effect, is
      frequently used. CsA has immunosuppressive effects following systemic
      application. Following local administration of CsA, it is expected to obtain
      effective drug concentration at the target area and to avoid the various side
      effects associated with systemic delivery. Microspheres, implants, and liposomes
      have been developed for administration of CsA subconjunctivally in order to
      enhance its efficiency.

PMID- 22619626
TI  - Economic impact of infected total knee arthroplasty.
AB  - BACKGROUND: An enormous economic impact can be observed for infected total knee
      arthroplasties (TKA). The aim of the present study was to evaluate whether a cost
      covering treatment of infected TKA is feasible in the German DRG System. PATIENTS
      AND METHODS: Average total treatment costs were evaluated for infected TKA and
      compared with a matched pair of primary TKA. Data was generated using the health
      record and the hospitals' health information system. Results were evaluated and
      compared regarding the total personnel and material costs with respect to the
      financial receipts. RESULTS: A total of 28 patients diagnosed with an infected
      TKA were included. A significant increase in the average length of stay, use of
      medical supplies and third party medical examinations were found for the infected
      TKA. An average deficiency of 6,356? per patient was observed for the infected
      TKA. An average profit of 927? per patient was made performing primary TKA.
      CONCLUSIONS: A cost-effective treatment of infected TKA was not feasible with the
      receipts from the German DRG System. An adaption of the receipts has to be
      evaluated. Moreover, other measures have to be considered in order to achieve a
      comprehensive medical yet financial reasonable standard in the treatment of
      infected TKA and THA.

PMID- 22619627
TI  - The effect of an enamel matrix derivative (Emdogain) combined with bone ceramic
      on bone formation in mandibular defects: a histomorphometric and
      immunohistochemical study in the canine.
AB  - BACKGROUND: The purpose of this study was to evaluate the combination of an
      enamel matrix derivative (EMD) and an osteoconductive bone ceramic (BC) in
      improving bone regeneration. MATERIALS AND METHODS: Four cylindrical cavities (6
      * 6 mm) were prepared bilaterally in the mandible in three dogs. The defects were
      randomly assigned to four different treatments-filled with EMD/BC and covered
      with a nonresorbable membrane, filled with EMD/BC without membrane, membrane
      coverage only, or control (left untreated)-and healed for 2, 4, or 6 weeks.
      Harvested specimens were prepared for histologic, histomorphometric, and
      immunohistochemical analyses. RESULTS: Sites treated with EMD/BC with or without
      membrane showed more total bone formation and lamellar bone formation than
      membrane-only and control defects. There were no statistically significant
      differences in total bone formation between EMD/BC with or without membrane.
      CONCLUSION: EMD with BC might improve bone formation in osseous defects more than
      membrane coverage alone; the use of a membrane had no significant additive effect
      on total bone formation.

PMID- 22619628
TI  - The use of silver solid amalgam electrodes for voltammetric and amperometric
      determination of nitrated polyaromatic compounds used as markers of incomplete
      combustion.
AB  - Genotoxic nitrated polycyclic aromatic hydrocarbons (NPAHs) are formed during
      incomplete combustion processes by reaction of polycyclic aromatic hydrocarbons
      (PAHs) with atmospheric nitrogen oxides. 1-Nitropyrene, 2-nitrofluorene, and 3
      nitrofluoranthene as the dominating substances are used as markers of NPAHs
      formation by these processes. In the presented study, voltammetric properties and
      quantification of these compounds and of 5-nitroquinoline (as a representative of
      environmentally important genotoxic heterocyclic compounds) have been
      investigated using a mercury meniscus modified silver solid amalgam electrode (m
      AgSAE), which represent a nontoxic alternative to traditional mercury electrodes.
      Linear calibration curves over three orders of magnitude and limits of
      determination mostly in the 10(-7) mol L(-1) concentration range were obtained
      using direct current and differential pulse voltammetry. Further, satisfactory
      HPLC separation of studied analytes in fifteen minutes was achieved using 0.01
      mol L(-1) phosphate buffer, pH 7.0 : methanol (15 : 85, v/v) mobile phase, and
      C(18) reversed stationary phase. Limits of detection of around 1 . 10(-5) mol L(
      1) were achieved using amperometric detection at m-AgSAE in wall-jet arrangement
      for all studied analytes. Practical applicability of this technique was
      demonstrated on the determination of 1-nitropyrene, 2-nitrofluorene, 3
      nitrofluoranthene, and 5-nitroquinoline in drinking water after their preliminary
      separation and preconcentration using solid phase extraction with the limits of
      detection around 1 . 10(-6) mol L(-1).

PMID- 22619629
TI  - Medicinal and environmental indicator species of Utricularia from montane forest
      of Peninsular Malaysia.
AB  - The carnivorous Utricularia (Lentibulariaceae) is a small herb of multifarious
      wet habitats worldwide. Eleven of the 14 Peninsular Malaysian species range into
      the mountains. Distribution, disturbance adaptability and collection frequency
      were used to formulate their commonness category. Common (U. aurea, U. bifida,
      and U. minutissima) and fairly common (U. gibba and U. uliginosa) species are
      mostly lowland plants that ascend to open montane microhabitats, while the fairly
      common (U. striatula), narrow-range (U. caerulea pink form and U. involvens),
      rare (U. furcellata and U. scandens), and endemic (U. vitellina) species are
      restricted to mountainous sites. Common species that colonise dystrophic to
      oligotrophic man-made sites in late succession could serve as predictors for
      general health and recovery of wet habitats. Rarer species are often locally
      abundant, their niches situated around pristine forest edges. When in decline,
      they indicate the beginning of problems affecting the forest. Utricularia is
      reportedly nutritious, mildly astringent, and diuretic. Preadapted to nutrient
      poor, waterlogged soils, U. bifida is suitable as an alternative for small-scale
      herb cultivation on low pH, wet poor soils usually deemed not suitable for any
      crops.

PMID- 22619630
TI  - Development and evaluation of a positive youth development course for university
      students in Hong Kong.
AB  - With higher education, university graduates are important elements of the labor
      force in knowledge-based economies. With reference to the mental health and
      developmental problems in university students, there is a need to review
      university's role in nurturing holistic development of students. Based on the
      positive youth development approach, it is argued that promoting intrapersonal
      competencies is an important strategy to facilitate holistic development of young
      people in Hong Kong. In The Hong Kong Polytechnic University, a course entitled
      Tomorrow's Leader focusing on positive youth development constructs to promote
      student well-being will be offered on a compulsory basis starting from 2012/13
      academic year under the new undergraduate curriculum structure. The proposed
      course was piloted in 2010/11 school year. Different evaluation strategies,
      including objective outcome evaluation, subjective outcome evaluation, process
      evaluation, and qualitative evaluation, are being carried out to evaluate the
      developed course. Preliminary evaluation findings based on the piloting
      experience in 2010/11 academic year are presented in this paper.

PMID- 22619631
TI  - A comparitive assessement of cytokine expression in human-derived cell lines
      exposed to alpha particles and X-rays.
AB  - Alpha- (alpha-) particle radiation exposure has been linked to the development of
      lung cancer and has been identified as a radiation type likely to be employed in
      radiological dispersal devices. Currently, there exists a knowledge gap
      concerning cytokine modulations associated with exposure to alpha-particles. Bio
      plex technology was employed to investigate changes in proinflammatory cytokines
      in two human-derived cell lines. Cells were irradiated at a dose of 1.5 Gy to
      either alpha-particles or X-rays at equivalent dose rates. The two cell lines
      exhibited a unique pattern of cytokine expression and the response varied with
      radiation type. Of the 27 cytokines assessed, only vascular endothelin growth
      factor (VEGF) was observed to be modulated in both cell lines solely after alpha
      particle exposure, and the expression of VEGF was shown to be dose responsive.
      These results suggest that certain proinflammatory cytokines may be involved in
      the biological effects related to alpha- particle exposure and the responses are
      cell type and radiation type specific.

PMID- 22619633
TI  - What Is the Status Quo of Breast Cancer Research at Germany's Universities?

PMID- 22619632
TI  - Acute and chronic toxicity of soluble fractions of industrial solid wastes on
      Daphnia magna and Vibrio fischeri.
AB  - Industrial wastes may produce leachates that can contaminate the aquatic
      ecosystem. Toxicity testing in acute and chronic levels is essential to assess
      environmental risks from the soluble fractions of these wastes, since only
      chemical analysis may not be adequate to classify the hazard of an industrial
      waste. In this study, ten samples of solid wastes from textile, metal-mechanic,
      and pulp and paper industries were analyzed by acute and chronic toxicity tests
      with Daphnia magna and Vibrio fischeri. A metal-mechanic waste (sample MM3)
      induced the highest toxicity level to Daphnia magna(CE(50,48 h) = 2.21%). A
      textile waste induced the highest toxicity level to Vibrio fischeri (sample TX2,
      CE(50,30 min) = 12.08%). All samples of pulp and paper wastes, and a textile
      waste (sample TX2) induced chronic effects on reproduction, length, and longevity
      of Daphnia magna. These results could serve as an alert about the environmental
      risks of an inadequate waste classification method.

PMID- 22619634
TI  - Breast Cancer Proteomics - Differences in Protein Expression between Estrogen
      Receptor-Positive and -Negative Tumors Identified by Tandem Mass Tag Technology.
AB  - BACKGROUND: Proteomic analysis has become an effective tool in breast cancer
      research. In this study, we applied the new gel-free tandem mass tag (TMT)
      reference method for the first time in breast cancer.  MATERIALS AND METHODS:
      Proteomic analysis was used to compare 10 estrogen receptor (ER)-positive and 10
      ER-negative samples. The results of the proteomic approach were validated by
      Western blot, immunohistochemistry and gene expression analysis.  RESULTS: 17
      proteins with significant differences in expression were identified. 13 proteins
      were overexpressed in ER-negative tumors and 4 were overexpressed in ER-positive
      samples. All these proteins were characterized by relatively high cellular
      abundance.  CONCLUSIONS: Our results demonstrate that the gel-free TMT approach
      allows the quantification of differences in protein expression levels. Further
      improvement of the sensitivity by subfractionation of the tissue should allow
      also the identification of low-abundance proteins and might lead to the use of
      this method in breast cancer research.

PMID- 22619635
TI  - Observer Variability of the Breast Imaging Reporting and Data System (BI-RADS)
      Lexicon for Mammography.
AB  - AIM: We aimed to determine the inter- and intra-observer variabilities between
      breast radiologists and a general radiologist in categorizing mammographic
      lesions using the Breast Imaging Reporting and Data System (BI-RADS), and to
      evaluate the effects of the histopathologic results on the variability.  METHODS:
      Mammograms from 142 women who underwent biopsy were evaluated. 3 breast
      radiologists (2 with >10 years experience and 1 with 1 year experience) and 1
      general radiologist retrospectively reviewed mammograms twice within an 8-week
      interval. Inter- and intra-observer variabilities were assessed with Cohen's
      kappa statistic, and the positive predictive value for final assessments was
      calculated.  RESULTS: The intra-observer variability for mass and calcification
      assessments was moderate to almost perfect (kappa values: 0.41-1) for breast
      imagers and was fair to substantial for the general radiologist (kappa values:
      0.21-0.8). Inter-observer agreement between the breast imagers was higher than
      between the breast and general radiologists. There was no apparent difference in
      agreement between observers for malignant and benign subgroups.  CONCLUSIONS: The
      differences in intra- and inter-observer agreement between the breast imagers and
      the general radiologist affirm the utility of the BI-RADS lexicon. The
      histopathologic results of the lesions do not affect the agreement. BI-RADS is a
      simple and adequate tool for assessing mammograms, even after only 1 year of
      training.

PMID- 22619636
TI  - Phase II Evaluation of Liposomal Doxorubicin with Docetaxel in Patients with
      Metastatic Breast Cancer.
AB  - BACKGROUND: Taxanes are effective in treating metastatic breast cancer. Liposomal
      doxorubicin (LD) is as effective as doxorubicin but less toxic.  PATIENTS AND
      METHODS: This phase II trial assessed the combination of LD and docetaxel (D).
      Between 12/2002 and 9/2005, 12 women received monthly LD (30 mg/m(2)) and weekly
      D (30 mg/m(2)). Cycles were continued until progression or toxicity. Primary
      outcome was time to progression. Secondary endpoints included response rate, time
      to treatment failure, duration of response, survival, and toxicity.  RESULTS:
      Median age was 49 (31-60) years. 9 (75%) patients had estrogen receptor-positive
      or progesterone receptor-positive tumors. 5 (41.7%) women had her-2/neu-positive
      tumors. 4 women stopped participation due to toxicity, and 7 due to progression.
      8 (67%) participants (95% confidence interval (CI) 51.6-94.5%) had a partial
      response, and 2 (16.7%) had stable disease. Median time to progression was 9.6
      months (95% CI 4.7-12.2). Median time to treatment failure was 6.5 months (95% CI
      4.4-10.5). Median survival was 22.1 months (95% CI 9.6-40.8). Median duration of
      partial response was 2.7 months (95% CI 2.4-10.5). 10 (83%) women experienced
      grade 3/4 toxicities: neutropenia 3 (25%), infection 3 (25%), stomatitis 5
      (41.7%), nausea 2 (16.7%), vomiting 1 (8.3%), dyspnea 2 (16.7%), pericardial
      effusion 1 (8.3), and palmar-plantar erythrodysesthesia 1 (8.3%).  CONCLUSIONS:
      LD and D resulted in an encouraging response and unacceptable toxicities.

PMID- 22619637
TI  - Metastasis of Primary Colon Cancer to the Breast - Leave Well Alone.
AB  - BACKGROUND: Metastasis to the breast is rare. Its management differs from that of
      primary breast cancer, as illustrated by this case of a colonic metastasis to the
      breast.  CASE REPORT: A 78-year-old woman presented with a breast lump 16 months
      after a palliative colonic resection for an obstructing colon cancer (T4 N0 M1).
      Core biopsy of the breast lump revealed morphological features identical to the
      original bowel cancer. In view of her progressive metastatic disease, the breast
      lump was simply observed. She passed away 4 months later from advanced intra
      abdominal carcinomatosis.  DISCUSSION: There are 19 cases of colonic metastasis
      to the breast in the literature. In the literature, colonic metastases to the
      breast are usually excised.  CONCLUSION: Excision of a colonic metastasis to the
      breast can be avoided if the patient's life expectancy is short.

PMID- 22619638
TI  - Usefulness of Preoperative Diagnosis with Magnetic Resonance Imaging for
      Conservative Surgery in Paget's Disease of the Breast.
AB  - BACKGROUND: Paget's disease (PD) of the breast is a relatively rare condition
      (incidence 1-3%) among primary breast cancers [6]. It presents with suggestive
      symptoms like erythema, nipple bleeding and ulceration.  PATIENT AND METHODS: A
      76-year-old woman was followed up for cancer of the left breast that had been
      operated 10 years before. During her annual check, a lesion suggestive of PD was
      detected. Mammography and ultrasound were performed, without evidence of a new
      breast lesion. In consideration of a possible underestimation of the real extent
      of the disease, we performed magnetic resonance imaging (MRI).  RESULTS: MRI
      showed an irregularly shaped tissue infiltrating the external side of the right
      breast. The pathologically bright signal involved the nipple and deformed the
      areolar skin. The characteristics of the increased signal were typical of a
      hypervascular invasive pattern and for tumoral neoangiogenesis. We performed a
      mastectomy with sentinel lymph node (SLN) biopsy, with evidence of a DIN 3
      carcinoma associated with PD of the nipple at the final pathology report. 
      CONCLUSION: The MRI was instrumental for the assessment of the existence and
      extent of malignant disease in a patient with PD but without a palpable lesion
      detectable with negative ultrasound and mammography.

PMID- 22619639
TI  - Recurrent Male Breast Cancer Accompanied by Carcinomatous Pleuritis That
      Responded to Combination Therapy with High-Dose Toremifene and Docetaxel.
AB  - BACKGROUND: Male breast cancer (MBC) is a rare disease with no standard treatment
      compared to female breast cancer. There are very few reports that go beyond
      second-line chemotherapy and endocrine therapy for advanced and recurrent MBC. 
      CASE REPORT: This report presents a case of recurrent MBC accompanied by
      carcinomatous pleuritis that responded to combination therapy with high-dose
      toremifene (TOR) and docetaxel (DOC). A 63-year-old male patient had previously
      undergone a modified radical mastectomy for left breast cancer and received
      several series of systemic chemotherapy and endocrine therapy. He complained of
      severe dyspnea, and was admitted to our hospital due to a massive left pleural
      effusion caused by carcinomatous pleuritis. He received combination therapy with
      high-dose TOR and biweekly DOC. The pleural effusion disappeared without any
      severe side effects after 4 cycles of the therapy. Thereafter, his disease
      stabilized for 1 year without re-increase of tumor markers under continuous
      treatment with the combination therapy.  CONCLUSIONS: High-dose TOR and DOC might
      be effective even beyond second-line chemotherapy and endocrine therapy for MBC
      to overcome potential multiple drug resistance and diminish inevitable side
      effects.

PMID- 22619640
TI  - Inflammatory Breast Diseases during Lactation: Milk Stasis, Puerperal Mastitis,
      Abscesses of the Breast, and Malignant Tumors - Current and Evidence-Based
      Strategies for Diagnosis and Therapy.
AB  - BACKGROUND: Breast diseases during the lactation period are of high importance
      because they can be an essential cause for early cessation of breastfeeding. 
      METHODS: To provide a comprehensive overview on the current recommendations of
      diagnostics and therapies, a systematic literature research was performed on a
      variety of online medical databases.  RESULTS: The primary aim of all therapy is
      a quick reduction of pain to allow continued breastfeeding. Each particular form
      of breast disease requires a specific therapy. These can range from conservative
      measures to antibiotics and surgical procedures. All therapeutic measures,
      including pharmacotherapy, are normally not an indication for cessation of
      breastfeeding.  CONCLUSION: Because the majority of breast diseases during the
      postnatal period occur only after the women have left the maternity clinics, all
      involved healthcare workers should educate women especially on preventive
      measures.

PMID- 22619641
TI  - Consumption of Cow's Milk and Possible Risk of Breast Cancer.

PMID- 22619642
TI  - The Challenge of Integrating Radiotherapy in the Multimodal Treatment of Breast
      Cancer.

PMID- 22619643
TI  - Should Postmastectomy Radiotherapy to the Chest Wall and Regional Lymph Nodes Be
      Standard for Patients with 1-3 Positive Lymph Nodes?
AB  - The indication for adjuvant postmastectomy radiotherapy (PMRT) in breast cancer
      patients with small tumors and 1-3 macrometastases in the axilla remains a
      controversial issue, despite the recommendation that PMRT should be applied in
      these patients in the most recent overview by the Early Breast Cancer Trialists'
      Collaborative Group. In this report, we discuss the available data on the benefit
      from PMRT in patients diagnosed with N1 breast cancer. Based on this, we
      recommend adjuvant PMRT to the chest wall and regional lymph nodes in patients
      diagnosed with early node-positive breast cancer.

PMID- 22619644
TI  - Axillary Irradiation as an Imperative Alternative to Axillary Dissection in
      Clinically Lymph Node-Negative but Sentinel Node-Positive Breast Cancer Patients?
AB  - At the moment, positive sentinel lymph node dissection (SLND) of the axilla is
      followed by axillary lymph node dissection (ALND) as standard of care. Recent
      data proves that omitting ALND after positive SLND in clinically lymph node
      negative early stage breast cancer patients is feasible with low recurrence
      rates. The well known effect of radiotherapy to destroy occult tumor cells highly
      contributes to these results as a large extent of level I and II lymph nodes are
      unavoidably included in standard tangential radiation treatment fields. Reviewing
      the up to date published data on axillary lymph node treatment with radiotherapy,
      we hypothesize that full dosage coverage of level I and II of the axilla in early
      stage breast cancer will improve outcome and should be further evaluated.

PMID- 22619645
TI  - Margins! Margins. Margins? How Important Is Margin Status in Breast-Preserving
      Therapy?
AB  - Margin status is surely a prognostic factor in patients undergoing breast
      conserving therapy, but its impact is probably overestimated in case of adequate
      adjuvant radiotherapy. Radiotherapy improves local control after excision of the
      primary tumor in all subgroups of patients. There is, in contrast, no evidence
      that a certain margin width or a re-resection improves local control.

PMID- 22619646
TI  - Does Radiotherapy Have Curative Potential in Metastatic Patients? The Concept of
      Local Therapy in Oligometastatic Breast Cancer.
AB  - In 1995, Hellmann and Weichselbaum defined for the first time the term
      oligometastases which is used to describe limited metastasis with a maximum of 3
      4 clinically detectable metastases. It is assumed that these patients have a
      better prognosis and that local treatment of the metastases plays a significant
      part in the further development of the disease. Therefore, these patients could
      benefit from a curative local therapy of the manifested metastases. Local therapy
      measures include mainly radiotherapeutic methods alongside invasive ablative
      processes, such as surgical resection and radiofrequency ablation. Patients
      subjected to radiation therapy benefit especially from the usage of modern
      precision technology as it reduces the radiation exposure to the normal tissue,
      and because short radiation sessions with escalating doses are possible (e.g.
      radiation surgery, image-assisted radiation therapy, stereotactic radiation).
      Initial clinical studies show very good local tumor control rates which are on a
      par with resection and ablative methods, but with very few side effects and
      risks. This article summarizes the integration of the concept of oligometastases
      in the radiotherapy of limited metastatic breast cancer.

PMID- 22619647
TI  - Late Toxicity of Radiotherapy: A Problem or a Challenge for the Radiation
      Oncologist?
AB  - BACKGROUND: Large randomized clinical trials have established radiotherapy in
      conjunction with adjuvant systemic treatment as standard treatment in breast
      cancer after both mastectomy and lumpectomy. Although standard radiation therapy
      is well tolerated by the majority of patients, some patients might suffer from
      late normal tissue effects.  METHODS: The literature on radiotherapy following
      surgery of breast cancer was reviewed with regard to late toxicity.  RESULTS:
      Radiotherapy may, to some degree, cause persistent pain in the breast, arm and
      shoulder in up to 30-50% of patients after 3-5 years, lymphedema in 15-25%, and
      restriction of arm and shoulder movement in 35%. Awareness of cardiotoxicity is
      needed since anthracyclines, trastuzumab, and radiotherapy may cause damage to
      the heart. However, using modern radiotherapy techniques, the available evidence
      does not suggest a higher incidence of cardiac mortality.  CONCLUSIONS: This
      review updates the database on toxicity from radiation in breast cancer. Advances
      in research of radiation-induced late effects may lead to improved treatment
      choices for breast cancer patients including radiotherapy and may improve quality
      of life after surviving breast cancer.

PMID- 22619648
TI  - Raising the Breast Health Awareness amongst Women in an Urban Slum Area in
      Alexandria, Egypt.
AB  - BACKGROUND: Breast Cancer (BC) is the most frequently occurring cancer among
      Egyptian women. This study aimed to determine the effectiveness of a health
      education program on raising the knowledge related to BC, its risk factors, and
      some related preventive practices among women living in an urban slum area in
      Alexandria.  PATIENTS AND METHODS: A pre-/post-test interventional study was
      conducted during 2009-2010 on a random sample of women aged 30-65 years (n = 486)
      living in a slum area in Alexandria, Egypt. 20 health education sessions were
      carried out to educate the women on BC risk factors and some preventive
      practices. Previously trained nurses educated the sampled women on breast self
      examination (BSE). The women's knowledge and opinion about BC and their practice
      of BSE were evaluated before and 3 months after the intervention.  RESULTS: The
      findings indicated a significant increase in the mean knowledge score regarding
      BC and the mean opinion score regarding some BC risk factors. A significant
      increase in the practice of BSE was observed post intervention.  CONCLUSION: This
      study confirms the effectiveness of intervention programs in improving the
      knowledge about BC risk factors and practice of BSE even in a group of women with
      a low literacy rate living in a slum area.

PMID- 22619649
TI  - Cost-Benefit Analysis of Endocrine Therapy in the Adjuvant Setting for
      Postmenopausal Patients with Hormone Receptor-Positive Breast Cancer, Based on
      Survival Data and Future Prices for Generic Drugs in the Context of the German
      Health Care System.
AB  - BACKGROUND: Cost-effectiveness analyses have focused on aromatase inhibitors
      (AIs), but the results are inconsistent and disease-free survival has often been
      extrapolated to overall survival. The present study calculates the cost
      effectiveness of 5 years of letrozole versus tamoxifen versus anastrozole in the
      context of the German health care system, using survival data from the Breast
      International Group (BIG) 1-98 study and the Arimidex, Tamoxifen, Alone or in
      Combination (ATAC) study and generic prices.  MATERIALS AND METHODS: A hybrid
      model was developed that incorporates recurrence rates, overall survival,
      treatment costs and treatment-associated adverse events and the resulting costs.
      The basic assumption was that generic anastrozole would lead to a price reduction
      to 75% of the original price. Further analyses were carried out with 50% and 25%
      of the original prices for anastrozole and letrozole.  RESULTS: The cost-benefit
      model showed a gain of 0.3124 or 0.0659 quality-adjusted life years (QALYs) for
      letrozole or anastrozole. Incremental costs of ? 29,375.15/QALY for letrozole
      (100% of original price) were calculated and ? 94,648.03/QALY for anastrozole
      (75% of original price). Marked increases in cost-effectiveness are observed with
      further decreases in price (anastrozole: 50% price ? 54,715.17/QALY, 25% price ?
      14,779.57/QALY; letrozole 75% price ? 20,988.59/QALY, 50% price ? 12,602.03/QALY,
      25% price ? 4,215.46/QALY).  CONCLUSION: The present model including the inverse
      probability of censoring weighted analysis (IPCW) for letrozole and generic
      prices for both AIs shows that letrozole is cost effective.

PMID- 22619650
TI  - An Unusual Case of Marginal Zone B-Cell Lymphoma Arising in the Breast - Its
      Diagnosis and the Role of Radiotherapy in its Management.
AB  - BACKGROUND: Primary lymphoma of the breast accounts for 0.04-0.5% of all breast
      malignancies and approximately 1% of all extranodal lymphomas. For stage IE node
      negative disease, involved field radiotherapy is recommended except for very
      young women in whom the risk of breast cancer is a concern. The rate of complete
      response for limited stage extranodal marginal B-cell lymphoma is in excess of
      90%.  CASE REPORT: We report the case of a 62-year-old lady who presented with a
      unilateral painless palpable right breast lump. She subsequently underwent a
      trucut biopsy of the lesion. The histology revealed a low-grade B-cell non
      Hodgkin's lymphoma (NHL). Immunohistochemistry showed that more than 95% of the
      cells were B cells which were CD 20+/CD 45+ and BC L6+. This confirmed the
      diagnosis of marginal zone lymphoma. Staging work-up was negative for distant
      metastases. Serum alkaline phosphatase and lactate dehydrogenase were normal. The
      patient had no 'B' symptoms. Her final diagnosis was clinical stage IAE NHL, and
      she was referred for curative radiotherapy.  CONCLUSION: Radiation treatment is a
      safe and extremely effective modality of treatment for early stage I marginal
      zone B-cell lymphomas of the breast.

PMID- 22619651
TI  - Preoperative Systemic Treatment in BRCA-Positive Breast Cancer Patients: Case
      Report and Review of the Literature.
AB  - BACKGROUND: In vitro and in vivo analyses have shown differences in
      chemosensitivity between breast cancers associated with BRCA1/2 mutations
      compared to sporadic variants. In the preoperative setting, the tumor response
      can be directly measured. Therefore, preoperative systemic treatment (PST) offers
      the opportunity to assess the chemosensitivity in vivo. However, there have been
      neither clear guidelines for mutation carriers in terms of choice of chemotherapy
      regimen nor recommendations how to proceed in case of an inadequate response to
      PST.  CASE REPORT: Herein, we present the history of a 39-year-old woman with
      bilateral breast cancer who was tested positive for germ-line BRCA1 mutation
      while under PST. We performed a comprehensive literature review covering the
      MEDLINE database from 1992 to 2010 on published data regarding PST options for
      BRCA mutation carriers.  CONCLUSIONS: If results of genetic testing are obtained
      during PST, individual therapy adaptations can be discussed with respect to
      mainly retrospective data of response to specific drugs. However, larger studies
      with longer follow-up are eagerly needed to draw firm conclusions before any
      specific treatment recommendations can be given for BRCA mutation carriers. PST
      is an ideal setting to evaluate such treatment options and to describe predictive
      markers that can help define subgroups that benefit most.

PMID- 22619652
TI  - Intracystic Papillary Carcinoma of the Breast in Males. In Search of the Optimal
      Treatment for this Rare Disease.
AB  - Intracystic papillary carcinoma (IPC) of the breast in men is an extremely
      infrequent disease, and it appears to have a good prognosis. Because of this,
      histological findings are of great importance in the decision-making process
      regarding treatment. Clinical examination, radiological and histological
      assessments are required for early detection. Adequate surgical excision with
      negative margins is mandatory. However, the role of sentinel node biopsy has not
      been evaluated in male IPC. It appears that sentinel node biopsy may be an
      excellent alternative to radical axillary dissection in patients with IPC and
      associated ductal carcinoma in situ or invasive carcinoma. Nevertheless, due to
      the rarity of IPC and its confusing histopathological classification and staging,
      there are still no clear guidelines as far as IPC treatment is concerned.

PMID- 22619653
TI  - Delayed-onset superior mesenteric artery syndrome presenting as oesophageal
      peptic stricture.
AB  - Superior mesenteric artery (SMA) syndrome is an infrequent cause of vomiting and
      weight loss due to compression of the third part of the duodenum by the SMA. We
      describe the case of a 17-year-old woman, admitted to our department for
      progressive dysphagia and severe weight loss due to an oesophageal peptic
      stricture, caused by chronic acid reflux secondary to duodenal compression by the
      SMA. Symptoms improved after (par)enteral nutrition and repeated oesophageal
      dilatation, thus supporting the role of intensive medical and endoscopic
      intervention as an alternative to surgery, at least in some cases.

PMID- 22619654
TI  - A case of severe esophageal intramural pseudodiverticulosis whose symptoms were
      ameliorated by oral administration of anti-fungal medicine.
AB  - Esophageal intramural pseudodiverticulosis (EIPD) is a rare disease of unknown
      etiology that displays multiple pseudodiverticula radiologically, leading to
      benign esophageal stricture. Dysphagia, which sometimes slowly progresses, is the
      main symptom in the majority of cases. We here report a 59-year-old male EIPD
      patient who suffered from severe dysphagia. Radiography and endoscopy of this
      patient disclosed a severe constriction in the upper thoracic esophagus. Although
      we tried several endoscopic procedures including frequent endoscopic balloon
      dilatation (EBD), the effect was very limited and his dysphagia relapsed shortly
      after the treatments. During the procedures, we noticed some white, thick, creamy
      liquid emerging from the orifices of EIPD, and PAS staining of biopsy specimens
      revealed infection with Candida albicans. Hence, the patient was given anti
      fungal medicine in addition to EBD. The additional treatment with anti-fungal
      medicine dramatically improved his symptoms and the esophageal constriction. This
      case suggests that anti-fungal treatment is an effective first-line therapy even
      against a severe form of esophageal constriction in EIPD.

PMID- 22619655
TI  - Ectopic cilia: a histopathological study.
AB  - Cilia are normally found at the eyelid margin, while ectopic cilia are one or
      more lash follicles appearing in an abnormal position within the eyelid. We
      herein report two cases of cilia located in the palpebral conjunctiva. A 31-year
      old female and a 46-year-old male presented with ectopic cilia in the superior
      palpebral conjunctiva. Histopathological study of the excised ectopic cilia and
      related lesions showed the cilia-related lesion to be located in the epithelial
      pit that contains goblet cells, which is consistent with the crypts of Henle. The
      hair follicle was surrounded by granulation tissue, while a dermal papilla and a
      hair matrix, which are known to produce hair follicles, did not exist in the
      excised tissue. While anterior ectopic cilia are congenital, ectopic cilia in the
      palpebral conjunctiva may be acquired, and these aberrant cilia are associated
      with crypts of Henle and chronic inflammation.

PMID- 22619656
TI  - Acute Cardiac Tamponade: An Unusual Cause of Acute Renal Failure.
AB  - We are reporting a case of acute renal failure after cardiac surgery due to acute
      pericardial effusion. The patient had normal baseline renal function but
      developed acute oliguric renal failure with a significant increase in serum
      creatinine postoperatively. Pericardiotomy led to an improvement in blood
      pressure, immediate diuresis and quick recovery of renal function back to
      baseline. Pericardial tamponade should be included in the consideration of causes
      of the cardiorenal syndrome.

PMID- 22619658
TI  - Systolic Heart Function, Kidney Filtration and the Number of Coronary
      Atherosclerotic Plaques in Lean and Overweight Patients.
AB  - The objective of this study was to quantify the number of vessels with stenotic
      points in the coronary circulation of lean and overweight individuals submitted
      to coronary angiography and ventriculography to verify the possible associations
      with glomerular filtration and the systolic ventricular function. Eighty-six
      patients with a previous history of myocardial ischemia were studied. Two groups
      were formed: non-elderly (G1), n = 38, 52.8 +/- 1.2 years old, and elderly (G2),
      n = 48, 70.1 +/- 1.2 years old. Both groups were divided into 2 subgroups
      according to the estimated glomerular filtration rate (eGFR): >=60 and <60
      ml/min/m(2). The results showed that G1 had 0.36 +/- 0.11 versus 1.25 +/- 0.45
      stenoses/patient (>=60 vs. <60 ml/min/m(2); p < 0.05, respectively) and G2 had
      0.91 +/- 0.28 versus 1.83 +/- 0.33 stenoses/patient (>=60 vs. <60 ml/min/m(2),
      respectively). The other variables, such as central and brachial arterial blood
      pressures, did not manifest significant differences in relation to the eGFR. The
      following significant correlations were observed: between the quantity of
      coronary stenotic points and the eGFR (R(2) = 11.2%; r = -0.33; p < 0.001), and
      between eGFR and the ventricular ejection fraction (R(2) = 5.1%; r = 0.57; p <
      0.0001). The ejection fraction correlated significantly with the number of
      vessels with stenoses in the coronary bed (R(2) = 13.4%; r = -0.36; p < 0.008).
      In conclusion, although the correlations are considered weak, interrelationships
      between heart and kidney were demonstrated in this study.

PMID- 22619659
TI  - A Validation Study of the Japanese Version of the Addenbrooke's Cognitive
      Examination-Revised.
AB  - The aim of this study was to validate the Japanese version of the Addenbrooke's
      Cognitive Examination-Revised (ACE-R) [Mori: Japanese Edition of Hodges JR's
      Cognitive Assessment for Clinicians, 2010] designed to detect dementia, and to
      compare its diagnostic accuracy with that of the Mini-Mental State Examination.
      The ACE-R was administered to 85 healthy individuals and 126 patients with
      dementia. The reliability assessment revealed a strong correlation in both
      groups. The internal consistency was excellent (alpha-coefficient = 0.88).
      Correlation with the Clinical Dementia Rating sum of boxes score was significant
      (r(s) = -0.61, p < 0.001). The area under the curve was 0.98 for the ACE-R and
      0.96 for the Mini-Mental State Examination. The cut-off score of 80 showed a
      sensitivity of 94% and a specificity of 94%. Like the original ACE-R and the
      versions designed for other languages, the Japanese version of the ACE-R is a
      reliable and valid test for the detection of dementia.

PMID- 22619657
TI  - Mitochondria and Oxidative Stress in the Cardiorenal Metabolic Syndrome.
AB  - Mitochondria play a fundamental role in the maintenance of normal structure,
      function, and survival of tissues. There is considerable evidence for
      mitochondrial dysfunction in association with metabolic diseases including
      insulin resistance, obesity, diabetes, and the cardiorenal metabolic syndrome.
      The phenomenon of reactive oxygen species (ROS)-induced ROS release through
      interactions between cytosolic and mitochondrial oxidative stress contributes to
      a vicious cycle of enhanced oxidative stress and mitochondrial dysfunction.
      Activation of the cytosolic and mitochondrial NADPH oxidase system, impairment of
      the mitochondrial electron transport, activation of p66shc pathway-targeting
      mitochondria, endoplasmic reticular stress, and activation of the mammalian
      target of the rapamycin-S6 kinase pathway underlie dysregulation of mitochondrial
      dynamics and promote mitochondrial oxidative stress. These processes are further
      modulated by acetyltransferases including sirtuin 1 and sirtuin 3, the former
      regulating nuclear acetylation and the latter regulating mitochondrial
      acetylation. The regulation of mitochondrial functions by microRNAs forms an
      additional layer of molecular control of mitochondrial oxidative stress. Alcohol
      further exacerbates mitochondrial oxidative stress induced by overnutrition and
      promotes the development of metabolic diseases.

PMID- 22619660
TI  - Impact of white matter lesions on cognition in stroke patients free from pre
      stroke cognitive impairment: a one-year follow-up study.
AB  - BACKGROUND/AIM: Post-stroke cognitive impairment and dementia may be caused by
      pure vascular, pure degenerative or mixed disease. The relation between post
      stroke cognitive impairment and the combination of vascular pathology and
      degenerative changes is less evaluated. We aimed to evaluate the associations
      between white matter lesions (WMLs) and patient performance 1 year after stroke
      on tests of executive functioning, memory and visuospatial function, adjusted for
      the effects of lifestyle and disease-related factors, including medial temporal
      lobe atrophy (MTLA). METHODS: Patients with a first-ever stroke or transient
      ischemic attack were invited to participate in the study. The associations
      between the cognitive test performances and WMLs were studied using linear
      regression [Trail Making Test B (TMT B) and 10-word test] and logistic regression
      (Clock Drawing Test). RESULTS: In total, 199 patients completed the follow-up.
      The TMT B (p = 0.029) and the 10-word test (p = 0.014) were significantly
      associated with WMLs; however, the Clock Drawing Test (p = 0.19) was not. The TMT
      B (p = 0.018) and the 10-word test (p <= 0.001) were both significantly
      associated with MTLA. CONCLUSION: Impaired executive functioning and memory are
      significantly associated with WMLs and MTLA. The mechanisms explaining post
      stroke cognitive impairment are multifactorial, including different types of
      vascular pathology and coexisting vascular and degenerative changes.

PMID- 22619661
TI  - CNS medications as predictors of precipitous cognitive decline in the cognitively
      disabled aged: a longitudinal population-based study.
AB  - BACKGROUND/AIMS: Psychotropics and antiepileptics (AE) are medications commonly
      used among the aged with cognitive decline or dementia, although they may
      precipitate further cognitive decline. Our aim was to analyze the relationships
      between the use of (i) psychotropics (i.e. benzodiazepines or related drugs, BZD,
      antipsychotics, AP, or antidepressants, AD), opioids (Op), anticholinergics (ACh)
      or AEs or the concomitant use of two of these drugs, and (ii) the risk of
      precipitous cognitive decline in an older (>=65 years) cognitively disabled
      population. METHODS: A longitudinal population-based study of general aged
      community-dwelling patients was executed in two phases (1990-1991 and 1998-1999)
      in Lieto, Finland. Fifty-two individuals cognitively disabled (MMSE score 0-23)
      at the 1990-1991 baseline form this study's sample. Cognitive abilities were
      assessed in each phase with the Mini-Mental State Examination (MMSE) and
      medication utilization data were collected in both phases. The mean follow-up
      time was 7.6 years. Multivariate models were used to analyze the change in MMSE
      total score between medication users and non-users. RESULTS: BZD or any
      psychotropic use was associated with greater cognitive decline in elders aged
      >=75 years compared to non-users (change in MMSE sum score: -8.6 +/- 7.0 vs. -3.3
      +/- 5.6 and -5.9 +/- 7.0 vs. -2.7 +/- 6.4, respectively). A greater decline was
      also associated specifically with the concomitant use of BZD and AP (-16 vs. -1.4
      +/- 7.8); as were BZD and any drug with CNS effects (-9.6 +/- 9.9 vs. -1.3 +/-
      7.2) compared to non-users. The concomitant use of BZD and AD (-10.7 +/- 4.7 vs. 
      3.2 +/- 5.6) or ACh (-15.0 +/- 8.5 vs. -3.3 +/- 5.6) or any drug with CNS effects
      (-13.3 +/- 6.5 vs. -3.3 +/- 5.6) was associated with cognitive decline in
      patients >=75 years compared to non-users of any drug with CNS effects.
      CONCLUSION: The use of a BZD or any psychotropic medication may be an independent
      risk factor for cognitive decline in the cognitively disabled aged, and patients
      co-prescribed psychotropic medications had greater cognitive decline. Studies
      with larger sample sizes and studies on possible pathophysiologic mechanisms are
      needed.

PMID- 22619662
TI  - Effect of cognitive and aerobic training intervention on older adults with mild
      or no cognitive impairment: a derivative study of the nakajima project.
AB  - BACKGROUND: An increasing elderly population in Japan requires effective
      cognitive intervention programs for dementia. This study demonstrates the
      effectiveness of such programs for older adults. METHODS: The participants were
      local community-dwelling non-demented older adults and adults with mild cognitive
      impairment who underwent executive function and group aerobic training. In
      addition, a non-intervention group participated in activity sessions involving
      handicraft, Skutt ball matches, and cooking. The four criteria for assessment
      were cognitive function, instrumental activities of daily living, human
      relationships, and physical function. RESULTS: The participants in both
      intervention groups showed a significant improvement in their memory function
      compared with the non-intervention group. CONCLUSION: Early rehabilitation
      intervention using executive function and aerobic training programs may improve
      memory.

PMID- 22619663
TI  - Response to the article by adanipar et Al.: the first report of a patient with
      probable variant creutzfeldt-jakob disease in Turkey, dement geriatr cogn disord
      extra 2011;1:429-432.

PMID- 22619664
TI  - Did They Really Perform Crimes due to Dementia?

PMID- 22619665
TI  - Socio-Cultural Perceptions and Representations of Dementia in Brazzaville,
      Republic of Congo: The EDAC Survey.
AB  - BACKGROUND: Dementia will concern more and more people in the developing
      countries, but the perception people have of dementia in these areas has not yet
      been studied. METHOD: During a general population survey (EDAC) carried out in
      Brazzaville (Republic of Congo), 27 elderly persons suspected of having dementia
      and 31 of their relatives, 90 cognitively impaired elderly persons and 92 of
      their relatives, as well as 33 hospital workers were interviewed according to the
      Explanatory Model Interview Catalogue. RESULTS: Item prominence ratings indicate
      that the attention was mainly on the emotional and socio-economic consequences
      (scores >1.0 out of 5 points). Ageing and mental stress are the main perceived
      causes. Hospital workers are more aware of public stigma. CONCLUSION: The socio
      cultural components of the dementia phenomenon have to be taken into account to
      enforce public health and social measures.

PMID- 22619666
TI  - The role of apelin on the alleviative effect of Angiotensin receptor blocker in
      unilateral ureteral obstruction-induced renal fibrosis.
AB  - BACKGROUND: Apelin is a selective endogenous ligand of the APJ receptor, which
      genetically has closest identity to the angiotensin II type 1 receptor (AT-1).
      The effects of the apelin/APJ system on renal fibrosis still remain unclear.
      METHODS: We examined the effects of the apelin/APJ system on renal fibrosis
      during AT-1 blockade in a mouse unilateral ureteral obstruction (UUO) model.
      RESULTS: WE OBTAINED THE FOLLOWING RESULTS: (1) At UUO day 7, mRNA expressions of
      apelin/APJ and phosphorylations of Akt/endothelial nitric oxide synthase (eNOS)
      in the UUO kidney were increased compared to those in the nonobstructed kidney.
      (2) AT-1 blockade by the treatment with losartan resulted in a further increase
      of apelin mRNA as well as phosphorylations of Akt/eNOS proteins, and this was
      accompanied by alleviated renal interstitial fibrosis, decreased myofibroblast
      accumulation, and a decreased number of interstitial macrophages. (3) Blockade of
      the APJ receptor by the treatment with F13A during losartan administration
      completely abrogated the effects of losartan in the activation of the Akt/eNOS
      pathway and the amelioration of renal fibrosis. (4) Inhibition of NOS by the
      treatment with L-NAME also resulted in a further increase in renal fibrosis
      compared to the control group. CONCLUSION: These results suggest that increased
      nitric oxide production through the apelin/APJ/Akt/eNOS pathway may, at least in
      part, contribute to the alleviative effect of losartan in UUO-induced renal
      fibrosis.

PMID- 22619667
TI  - Comparison of volume status in asymptomatic haemodialysis and peritoneal dialysis
      outpatients.
AB  - BACKGROUND: The majority of haemodialysis (HD) patients gain weight between
      dialysis sessions and thereby become volume overloaded, whereas peritoneal
      dialysis (PD) is a more continuous technique. Cardiovascular mortality and
      hypertension is increased with both treatment modalities. We therefore wished to
      compare volume status in PD and HD to determine whether PD patients are
      chronically volume overloaded, as a risk factor for cardiovascular mortality.
      Study Design, Setting and Participants:We retrospectively audited 72 healthy HD
      patients and 115 healthy PD patients attending a university hospital dialysis
      centre for routine outpatient treatment, who had multi-frequency bioimpedance
      measurements of extracellular water to total body water (ECW/TBW). RESULTS: The
      groups were well matched for age, sex, weight and ethnicity, PD patients had
      greater urine output [1,075 (485-1,613) vs. 42.5 (0-1,020) ml/day, p < 0.001],
      but there was no difference in antihypertensive prescription (63.5 vs. 76.4%),
      mean arterial blood pressure (post-dialysis 101.6 +/- 1.5 mm Hg vs. pre-dialysis
      102 +/- 2.4 mm Hg), although post-dialysis arterial blood pressure was lower than
      in PD patients (96.4 +/- 3.1 mm Hg, p < 0.05). The ratio of ECW/TBW fell after HD
      (pre-dialysis 0.394 +/- 0.001 vs. post-dialysis 0.389 +/- 0.004, p < 0.001) and
      was similar in the PD group to the group before HD (0.393 +/- 0.001), and greater
      than that in the group after HD (p < 0.001). ECW/TBW was greater than the normal
      reference range in 30% PD patients, 28% patients before HD and 20% patients after
      HD. CONCLUSIONS: Overhydration is common in healthy stable PD outpatients, and
      ECW volumes in PD patients are not dissimilar to those of pre-dialysis HD
      patients. The role of chronic volume overload as a risk factor for cardiovascular
      disease needs further investigation.

PMID- 22619669
TI  - Infectious risks and optimal strength of maintenance immunosuppressants in
      rituximab-treated kidney transplantation.
AB  - BACKGROUND: Rituximab, an anti-CD20 antibody, effectively depletes B lymphocytes.
      It is not clear whether the use of conventional doses of mycophenolate mofetil
      (MMF), methylprednisolone and tacrolimus as maintenance immunosuppression in
      rituximab-treated kidney transplantation is associated with increased risk.
      METHODS: We retrospectively evaluated 67 patients who underwent HLA-sensitized or
      ABO-incompatible living donor kidney transplantation after one dose of rituximab
      (200 or 500 mg) (group 1). Eighty-seven kidney transplant recipients who did not
      require rituximab served as a control (group 2). RESULTS: Cytomegalovirus
      infection (16.4 vs. 5.7%, p = 0.031) and pneumonia (9.0 vs. 1.1%, p = 0.043)
      occurred more often in group 1, and 2 patients of group 1 died of infection. The
      doses of methylprednisolone and tacrolimus levels of the two groups were not
      different. MMF dose was reduced when serious infection occurred. The doses of MMF
      (in grams/day) at the following times postoperatively were lower in group 1 than
      in group 2: 1 month: 1.26 +/- 0.42 vs. 1.40 +/- 0.39, p = 0.033; 3 months: 1.14
      +/- 0.51 vs. 1.36 +/- 0.39, p = 0.011; 6 months: 1.07 +/- 0.50 vs. 1.30 +/- 0.42,
      p = 0.012; 1 year: 0.88 +/- 0.52 vs. 1.19 +/- 0.44, p = 0.009; 2 years: 0.69 +/-
      0.55 vs. 1.25 +/- 0.49, p = 0.059, but the reduction of MMF doses did not
      increase the incidence of acute rejection in group 1 (4.5% in group 1 vs. 9.2% in
      group 2, p = 0.351). If patients who died with functioning graft were excluded,
      graft survival was 98.5% in group 1 and 100% in group 2. CONCLUSIONS: Serious
      infectious complications were increased in rituximab-treated kidney transplant
      recipients and it might be adequate to reduce the MMF dose from the early
      postoperative period.

PMID- 22619668
TI  - Hemodiafiltration improves plasma 25-hepcidin levels: a prospective, randomized,
      blinded, cross-over study comparing hemodialysis and hemodiafiltration.
AB  - BACKGROUND/AIMS: Data from studies comparing the effect of hemodiafiltration
      (HDF) and conventional hemodialysis (HD) on clinically important outcomes are
      insufficient to support superiority of HDF. None of these studies has been
      participant-blinded. METHODS: We performed a prospective, randomized, and patient
      blinded cross-over study. Twenty patients on chronic HD received either HD for 2
      months followed by post-dilution HDF for 2 months or in opposite order. A range
      of clinical parameters, as well as markers of inflammation, oxidative stress and
      iron metabolism was measured. RESULTS: The two treatments were similar with
      respect to dialysis-related complications, quality of life, and the biomarkers of
      oxidative stress and inflammation. Compared to HD, 25-hepcidin and beta(2)
      microglobulin were 38 and 32%, respectively, lower after 60 days of HDF (p <
      0.001 and p < 0.01, respectively). The consumption of ESA (erythropoietin
      stimulating agent) and LMWH (low-molecular-weight heparin) was significantly
      higher with HDF. CONCLUSION: In short term, HDF is not superior to HD regarding
      dialysis-related complications. The higher ESA consumption observed with HDF can
      be explained by blood clotting in tubing and dialyzers, as more anticoagulation
      was needed with post-dilution HDF. In a longer perspective, lowering serum
      hepcidin levels may improve pathological iron homeostasis.

PMID- 22619670
TI  - Association of HCV core antigen seropositivity with long-term mortality in
      patients on regular hemodialysis.
AB  - Anti-hepatitis C virus (HCV) antibody seropositivity is independently associated
      with poor prognosis in hemodialysis (HD) patients. However, anti-HCV antibody
      cannot distinguish between patients with active infection and those who have
      recovered from infection. We therefore aimed in this study to examine the
      association of HCV core antigen (HCVcAg) seropositivity with mortality in HD
      patients. We first measured serum HCVcAg using an immunoradiometric assay and
      anti-HCV antibody in 405 patients on regular HD, and followed them for 104
      months. There were 82 patients (20.2%) who had been positive for anti-HCV
      antibodies; 57 (69.5%) of these were positive for HCVcAg. During the follow-up,
      29 patients were excluded, so we tested the association of HCVcAg seropositivity
      with all-cause, cardiovascular (CV) and non-CV mortalities in 376 patients. A
      total of 209 patients (55.6%) had expired during the observational period, 92 out
      of them due to CV causes. After adjusting for comorbid parameters, HCVcAg was
      independently associated with overall mortality (HR 1.61, 95% CI 1.05-2.47, p <
      0.05). HCV infection was significantly related to liver disease-related
      mortality. Past HCV infection also contributed to CV mortality (HR 2.63, 95% CI
      1.27-5.45, p < 0.01). In contrast, anti-HCV antibody and HCVcAg seropositivities
      did not associate with infectious disease-related and cancer-related (expect for
      hepatocellular carcinoma) mortality. It follows from these findings that HCVcAg
      serology is associated with all-cause and CV mortality in HD patients.

PMID- 22619671
TI  - Osteopontin plays a critical role in interstitial fibrosis but not glomerular
      sclerosis in diabetic nephropathy.
AB  - BACKGROUND/AIMS: Osteopontin (OPN) has been implicated in the pathology of
      several renal conditions. The aim of this study was to clarify the roles of OPN
      in diabetic nephropathy. METHODS: Diabetes mellitus (DM) was induced in wild-type
      (WT) and OPN knockout (KO) mice by injecting streptozotocin. The mice were killed
      20 weeks after induction of DM and their kidneys removed. RESULTS: Renal mRNA
      expression of OPN was increased in WT-DM mice compared to WT-sham mice.
      Immunohistochemistry showed high levels of OPN expression in the proximal tubules
      of WT-DM mice. Kidney weight and urinary albumin excretion increased to similar
      levels in the WT-DM and KO-DM mice. Interstitial fibrosis was increased in WT-DM
      mice compared to KO-DM mice. However, there were no differences in the degree of
      mesangial expansion or glomerular hypertrophy between the two groups. F4/80
      positive cells (macrophages) and FSP-1-positive cells (fibroblasts) showed
      significantly higher infiltration in WT-DM mice than in KO-DM mice. Renal mRNA
      expression of NADPH oxidase subunits and urinary 8-isoprostane excretion were
      also increased in WT-DM mice. CONCLUSIONS: These results indicated that OPN is a
      key molecule that induces interstitial fibrosis in the diabetic kidney, but does
      not induce glomerular sclerosis.

PMID- 22619672
TI  - AS601245, an Anti-Inflammatory JNK Inhibitor, and Clofibrate Have a Synergistic
      Effect in Inducing Cell Responses and in Affecting the Gene Expression Profile in
      CaCo-2 Colon Cancer Cells.
AB  - PPARalphas are nuclear receptors highly expressed in colon cells. They can be
      activated by the fibrates (clofibrate, ciprofibrate etc.) used to treat
      hyperlipidemia. Since PPARalpha transcriptional activity can be negatively
      regulated by JNK, the inhibition of JNK activity could increase the effectiveness
      of PPARalpha ligands. We analysed the effects of AS601245 (a JNK inhibitor) and
      clofibrate alone or in association, on proliferation, apoptosis, differentiation
      and the gene expression profile of CaCo-2 human colon cancer cells. Proliferation
      was inhibited in a dose-dependent way by clofibrate and AS601245. Combined
      treatment synergistically reduced cell proliferation, cyclin D1 and PCNA
      expression and induced apoptosis and differentiation. Reduction of cell
      proliferation, accompanied by the modulation of p21 expression was observed in
      HepG2 cells, also. Gene expression analysis revealed that some genes were highly
      modulated by the combined treatment and 28 genes containing PPRE were up
      regulated, while clofibrate alone was ineffective. Moreover, STAT3 signalling was
      strongly reduced by combined treatment. After combined treatment, the binding of
      PPARalpha to PPRE increased and paralleled with the expression of the PPAR
      coactivator MED1. Results demonstrate that combined treatment increases the
      effectiveness of both compounds and suggest a positive interaction between
      PPARalpha ligands and anti-inflammatory agents in humans.

PMID- 22619673
TI  - Integrated Use of Biomarkers (O : N Ratio and Acetylcholinesterase Inhibition) on
      Aulacomya ater (Molina, 1782) (Bivalvia: Mytilidae) as a Criteria for Effects of
      Organophosphate Pesticide Exposition.
AB  - The effect of residual concentrations of organophosphate pesticide chlorpyrifos
      (Lorsban 4E) on the activity of the acetylcholinesterase enzyme and oxygen :
      nitrogen ratio in the mussel Aulacomya ater was analyzed. Toxicity tests show a
      sensitivity to the pesticide in the bivalve estimated at 16 MUg L(-1) (LC(50-96
      hours)). Concentrations between 0.2 and 1.61 MUg L(-1) were able to inhibit
      significantly the AChE activity, and concentrations between 0.8 and 1.61 MUg L(
      1) stimulate ammonia excretion and decrease oxygen : ammonia-N (O : N) ratio,
      with respect to the control group. A. ater proved to be a species sensitive to
      pesticide exposure and easy to handle in lab conditions. Thus, it is recommended
      as a bioindicator for use in programs of environmental alertness in the Eastern
      South Pacific coastal zone.

PMID- 22619674
TI  - Early detection of ovarian cancer with conventional and contrast-enhanced
      transvaginal sonography: recent advances and potential improvements.
AB  - Recently, there have been several major technical advances in the sonographic
      diagnosis of ovarian cancer in its early stages. These include improved
      assessment of tumor morphology with transvaginal sonography (TVS), and detection
      and characterization of tumor neovascularity with transvaginal color Doppler
      sonography (TV-CDS) and contrast-enhanced transvaginal sonography (CE-TVS). This
      paper will discuss and illustrate these improvements and describe how they
      enhance detection of early-stage ovarian cancer. Our initial experience with
      parametric mapping of CE-TVS will also be mentioned.

PMID- 22619675
TI  - Burden of Human Papillomavirus among Haitian Immigrants in Miami, Florida:
      Community-Based Participatory Research in Action.
AB  - Background. Haitian immigrant women residing in Little Haiti, a large ethnic
      enclave in Miami-Dade County, experience the highest cervical cancer incidence
      rates in South Florida. While this disparity primarily reflects lack of access to
      screening with cervical cytology, the burden of human papillomavirus (HPV) which
      causes virtually all cases of cervical cancer worldwide, varies by population and
      may contribute to excess rate of disease. Our study examined the prevalence of
      oncogenic and nononcogenic HPV types and risk factors for HPV infection in Little
      Haiti. Methods. As part of an ongoing community-based participatory research
      initiative, community health workers recruited study participants between 2007
      and 2008, instructed women on self-collecting cervicovaginal specimens, and
      collected sociodemographic and healthcare access data. Results. Of the 242 women
      who contributed adequate specimens, the overall prevalence of HPV was 20.7%, with
      oncogenic HPV infections (13.2% of women) outnumbering nononcogenic infections
      (7.4%). Age-specific prevalence of oncogenic HPV was highest in women 18-30 years
      (38.9%) although the prevalence of oncogenic HPV does not appear to be elevated
      relative to the general U.S. population. The high prevalence of oncogenic types
      in women over 60 years may indicate a substantial number of persistent infections
      at high risk of progression to precancer.

PMID- 22619676
TI  - Overexpression of eIF3a in Squamous Cell Carcinoma of the Oral Cavity and Its
      Putative Relation to Chemotherapy Response.
AB  - The eukaryotic translation initiation factor eIF3a is one of the core subunits of
      the translation initiation complex eIF3, responsible for ribosomal subunit
      joining and mRNA recruitment to the ribosome. It is known to play an important
      role in general translation initiation as well as in the specific translational
      regulation of various gene products, among which many influence tumour
      development, progression, and the therapeutically important pathways of DNA
      damage repair. Therefore, beyond its role in protein synthesis, eIF3a is emerging
      as regulator in tumour pathogenesis and therapy response and, therefore, a
      potential tumor marker. By means of a tissue microarray (TMA) for
      histopathological and statistical assessment, we here show eIF3a expression in
      103 cases of squamous cell carcinoma of the oral cavity (OSCC), representing
      tissues from 103 independent patients. A subset of the study cohort was treated
      with platinum based therapy. Our results show that the 170 kDa protein is
      upregulated in OSCC and correlates with good overall survival. Overexpressing
      tumors respond better to platinum-based chemotherapy, suggesting eIF3a as a
      putative predictive as well as prognostic tumor marker in OSCC.

PMID- 22619677
TI  - Altered p16(INK4) and RB1 Expressions Are Associated with Poor Prognosis in
      Patients with Nonsmall Cell Lung Cancer.
AB  - p16(INK4) and RB1 are two potent cell cycle regulators to control the G1/S
      transition by interacting with CDK4/6, E2F, and D-type cyclins, respectively.
      Depending on the tumour type, genetic alterations resulting in the functional
      inactivation have frequently been reported in both genes. By contrast, much less
      is known regarding the overexpression of these proteins in the tumor cells. In
      this study, expressions of p16(INK4) RB1, and CDKN2A copy number variances (CNV)
      in the tumor cells were assessed by immunohistochemistry and fluorescence in situ
      hybridization (FISH), respectively, in 73 nonsmall cell lung cancer (NSCLC) with
      known 5-year survivals. The histologic type (P = 0.01), p16(INK4) (P = 0.004),
      and RB1 (P < 0.001) were predictive of survivals. The CDKN2A CNV (P < 0.05) was
      also significant when compared to those cases without CNV. Therefore, among the
      molecular genetic prognostic factors, expressions of RB1 and p16(INK4) in the
      tumor cells were the most strongly predictive of adverse outcomes in stage I and
      II nonsquamous NSCLC.

PMID- 22619678
TI  - The current practice of screening, prevention, and treatment of androgen
      deprivation-therapy induced osteoporosis in patients with prostate cancer.
AB  - Introduction. ADT is used in the management of locally advanced and metastatic
      disease. The detrimental effect of ADT on bone density is well documented. This
      study assesses care gaps in screening, prevention and treatment of osteoporosis
      among prostate cancer patients. Methods. We conducted a retrospective cohort
      study for patients diagnosed with non-metastatic prostate cancer on ADT. Charts
      from a tertiary oncology center were assessed for utilization of DXA scan,
      prescription of calcium, vitamin D, calcitonin and bisphosphonates.Bivariate
      analysis was used to determine the effect of patient characteristics and
      likelihood for osteoporosis screening. Results. 149 charts were reviewed, with 3
      year mean follow-up. 58.8% of men received a baseline DXA, of which 20.3% had a
      repeat DXA within their follow-up periods.In all, 28% were appropriately screened
      and managed for osteoporosis (received repeat DXA, bisphosphonate). In bivariate
      analysis, the number of ADT injections which correlate with the duration of
      androgen suppression was significantly associated with the number of DXA scans.
      Conclusions. Our study found a care gap in the screening, prevention, and
      treatment of osteoporosis in this population. Patients receiving the most ADT
      injections were more likely to be screened. Our results suggest healthcare
      providers treating prostate cancer are insufficiently screening and treating this
      susceptible population. We suggest baseline measurement of BMD at the initiation
      of ADT with periodic reassessment during therapy.

PMID- 22619679
TI  - Retinoblastoma in the democratic republic of congo: 20-year review from a
      tertiary hospital in kinshasa.
AB  - Background. To determine clinical profile and management of retinoblastoma among
      children at Kinshasa in Democratic Republic of Congo. Patients and methods. The
      medical records of patients with a diagnosis of retinoblastoma seen at the
      University Hospital of Kinshasa from January 1985 till December 2005 were
      retrospectively reviewed. Demographic profile, clinical data, modes of treatment
      and outcome were analysed. Results. A total of 49 children, of whom 40 had
      adequate data on record were identified as retinoblastoma (28 males and 12
      females). Nine cases had bilateral disease. The median age at the first symptoms
      was 9 months (range, 1 month to 6 years) for unilateral retinoblastoma and 18
      months (range, 1 month to 3.5 years) for bilateral retinoblastoma. The median age
      at the first oncology consultation was 2.4 years (range, 6 months to 6 years) for
      unilateral retinoblastoma and 2.4years (range, 9 months to 4 years) for bilateral
      disease. Leukokoria was present in 67.5% of subjects. Seventy-five percent
      abandoned the treatment. The mortality was 92.5%. Conclusion. In Democratic
      Republic of Congo, retinoblastoma remains a life threatening disease
      characterized by late referral to a specialized unit and affordability of
      chemotherapy; all leading to an extension of the disease and high mortality.

PMID- 22619681
TI  - Complications of Uterine Fibroids and Their Management, Surgical Management of
      Fibroids, Laparoscopy and Hysteroscopy versus Hysterectomy, Haemorrhage,
      Adhesions, and Complications.
AB  - A critical analysis of the surgical treatment of fibroids compares all available
      techniques of myomectomy. Different statistical analyses reveal the advantages of
      the laparoscopic and hysteroscopic approach. Complications can arise from the
      location of the fibroids. They range from intermittent bleedings to continuous
      bleedings over several weeks, from single pain episodes to severe pain, from
      dysuria and constipation to chronic bladder and bowel spasms. Very seldom does
      peritonitis occur. Infertility may result from continuous metro and menorrhagia.
      The difficulty of the laparoscopic and hysteroscopic myomectomy lies in achieving
      satisfactory haemostasis using the appropriate sutures. The hysteroscopic
      myomectomy requires an operative hysteroscope and a well-experienced gynaecologic
      surgeon.

PMID- 22619680
TI  - Reproductive late effects in female survivors of childhood cancer.
AB  - Childhood cancer treatments can cause female reproductive late effects. Radiation
      to the hypothalamic-pituitary-ovarian axis is associated with altered menarche,
      miscarriage, and implantation failure. Patients who receive chemotherapy and/or
      ovarian radiation are at risk of premature ovarian failure; the risk increases
      with increasing radiation dose, alkylating agent score, combination therapy, and
      older age at treatment. Ovarian reserve may be assessed using antimullerian
      hormone assay and ultrasound measurements of ovarian volume and antral follicle
      count; however, their efficacy is poorly established in this cohort. Fertility
      preservation options including cryopreservation, oophoropexy, and gonadotropin
      releasing hormone analogues may be initiated prior to treatment, although most
      are still considered experimental. Uterine radiation has been linked to pregnancy
      complications including miscarriage, premature delivery, stillbirth, low-birth
      weight and small-for-gestational-age infants. This paper summarises the
      literature on female reproductive late effects. The information should facilitate
      counseling and management of female survivors throughout their reproductive
      lives.

PMID- 22619682
TI  - Temporal Requirements of cMyc Protein for Reprogramming Mouse Fibroblasts.
AB  - Exogenous expression of Oct4, Sox2, Klf4, and cMyc forces mammalian somatic cells
      to adopt molecular and phenotypic characteristics of embryonic stem cells,
      commencing with the required suppression of lineage-associated genes (e.g., Thy1
      in mouse). Although omitting cMyc from the reprogramming cocktail minimizes risks
      of uncontrolled proliferation, its exclusion results in fold reductions in
      reprogramming efficiency. Thus, the feasibility of substituting cMyc transgene
      with (non-integrative) recombinant "pTAT-mcMyc" protein delivery was assessed,
      without compromising reprogramming efficiency or the pluripotent phenotype.
      Purification and delivery of semisoluble/particulate pTAT-mcMyc maintained Oct4
      GFP(+) colony formation (i.e., reprogramming efficiency) whilst supporting
      pluripotency by various criteria. Differential repression of Thy1 by pTAT-mcMyc
      +/- Oct4, Sox2, and Klf4 (OSK) suggested differential (and non-additive)
      mechanisms of repression. Extending these findings, attempts to enhance
      reprogramming efficiency through a staggered approach (prerepression of Thy1)
      failed to improve reprogramming efficiency. We consider protein delivery a useful
      tool to decipher temporal/molecular events characterizing somatic cell
      reprogramming.

PMID- 22619683
TI  - Stimulation of cultured h9 human embryonic stem cells with thyroid stimulating
      hormone does not lead to formation of thyroid-like cells.
AB  - The sodium-iodine symporter (NIS) is expressed on the cell membrane of many
      thyroid cancer cells, and is responsible for the radioactive iodine accumulation.
      However, treatment of anaplastic thyroid cancer is ineffective due to the low
      expression of NIS on cell membranes of these tumor cells. Human embryonic stem
      cells (ESCs) provide a potential vehicle to study the mechanisms of NIS
      expression regulation during differentiation. Human ESCs were maintained on
      feeder-independent culture conditions. RT-qPCR and immunocytochemistry were used
      to study differentiation marker expression, (125)I uptake to study NIS function.
      We designed a two-step protocol for human ESC differentiation into thyroid-like
      cells, as was previously done for mouse embryonic stem cells. First, we obtained
      definitive endoderm from human ESCs. Second, we directed differentiation of
      definitive endoderm cells into thyroid-like cells using various factors, with
      thyroid stimulating hormone (TSH) as the main differentiating factor. Expression
      of pluripotency, endoderm and thyroid markers and (125)I uptake were monitored
      throughout the differentiation steps. These approaches did not result in
      efficient induction of thyroid-like cells. We conclude that differentiation of
      human ESCs into thyroid cells cannot be induced by TSH media supplementation
      alone and most likely involves complicated developmental patterns that are yet to
      be understood.

PMID- 22619684
TI  - Stem cells as in vitro model of Parkinson's disease.
AB  - Progress in understanding neurodegenerative cell biology in Parkinson's disease
      (PD) has been hampered by a lack of predictive and relevant cellular models. In
      addition, the lack of an adequate in vitro human neuron cell-based model has been
      an obstacle for the uncover of new drugs for treating PD. The ability to generate
      induced pluripotent stem cells (iPSCs) from PD patients and a refined capacity to
      differentiate these iPSCs into DA neurons, the relevant disease cell type,
      promises a new paradigm in drug development that positions human disease
      pathophysiology at the core of preclinical drug discovery. Disease models derived
      from iPSC that manifest cellular disease phenotypes have been established for
      several monogenic diseases, but iPSC can likewise be used for phenotype-based
      drug screens in complex diseases for which the underlying genetic mechanism is
      unknown. Here, we highlight recent advances as well as limitations in the use of
      iPSC technology for modelling PD "in a dish" and for testing compounds against
      human disease phenotypes in vitro. We discuss how iPSCs are being exploited to
      illuminate disease pathophysiology, identify novel drug targets, and enhance the
      probability of clinical success of new drugs.

PMID- 22619685
TI  - Early Pollen Sensitization in Children Is Dependent upon Regional Aeroallergen
      Exposure.
AB  - Introduction. Aeroallergen sensitization occurs at an earlier age than previously
      noted. The purpose of this paper was to identify which pollens cause early
      sensitization in young children presenting with rhinitis symptoms. Methods. This
      paper was a retrospective analysis of skin test results from 2- to 8-year-old
      patients presenting with a history consistent with allergic rhinitis. Patients
      were tested to aeroallergens common to the Great Basin along with a histamine and
      saline control. Pollen counts were obtained from a Reno, NV-certified counting
      station. Results. 123 children less than 8 years of age were identified. Over 50%
      of these children were sensitized to at least one aeroallergen. Chemopodaciae,
      timothy, alfalfa, black walnut, olive, mountain cedar and willow were
      predominating sensitizing aeroallergens of the Great Basin Region. Pollen counts
      were notable for a early spring peak for the tree season, grass season in May and
      weed season in August. Pollen levels continued to November at low levels.
      Discussion. Aeroallergens causing early sensitization differed from those which
      had predominately been reported in other regions of the United States. Pediatric
      allergists should consider performing a local review of sensitizing aeroallergens
      in their region to assist with identification and management of allergic rhinitis
      in their youngest patients. Please make style changes as appropriate.

PMID- 22619686
TI  - Skin barrier function and its importance at the start of the atopic march.
AB  - Atopic dermatitis can be due to a variety of causes from nonatopic triggers to
      food allergy. Control of egress of water and protection from ingress of irritants
      and allergens are key components of cutaneous barrier function. Current research
      suggests that a degraded barrier function of the skin allows the immune system
      inappropriate access to environmental allergens. Epidermal aeroallergen exposure
      may allow sensitization to allergen possibly initiating the atopic march. Further
      research into connections between epidermal barrier function and possible
      allergen sensitization will be important to undertake. Future clinical trials
      focused on skin barrier protection may be of value as a possible intervention in
      prevention of the initiation of the atopic march.

PMID- 22619687
TI  - Environmental pollution: health effects and operational implications for
      pollutants removal.

PMID- 22619688
TI  - Reshuffling and relocating: the gendered and income-related differential effects
      of restricting smoking locations.
AB  - This study investigates secondhand smoke (SHS) exposure and management in the
      context of smoking location restrictions, for nonsmokers, former, and current
      smokers. A purposive sample of 47 low income and non-low-income men and women of
      varied smoking statuses was recruited to participate in a telephone interview or
      a focus group. Amidst general approval of increased restrictions there were
      gendered patterns of SHS exposure and management, and effects of SHS policies
      that reflect power, control, and social roles that need to be considered as
      policies are developed, implemented and monitored. The experience of smoking
      restrictions and the management of SHS is influenced by the social context
      (relationship with a partner, family member, or stranger), the space of exposure
      (public or private, worksite), the social location of individuals involved
      (gender, income), and differential tolerance to SHS. This confluence of factors
      creates differing unintended and unexpected consequences to the social and
      physical situations of male and female smokers, nonsmokers, and former smokers.
      These factors deserve further study, in the interests of informing the
      development of future interventions and policies restricting SHS.

PMID- 22619690
TI  - Rhynchophylline Protects Cultured Rat Neurons against Methamphetamine
      Cytotoxicity.
AB  - Rhynchophylline (Rhy) is an active component isolated from species of the genus
      Uncaria which has been used for the treatment of ailments to the central nervous
      system in traditional Chinese medicine. Besides acting as a calcium channel
      blocker, Rhy was also reported to be able to protect against glutamate-induced
      neuronal death. We thus hypothesize that Rhy may have neuroprotective activity
      against methamphetamine (MA). The primary neurons were cultured directly from the
      cerebral cortex of neonatal rats, acting as in vitro model in the present study.
      The neurotoxicity of MA and the protective effect of Rhy were evaluated by MTT
      assay. The effects of MA, Rhy or their combination on intracellular free calcium
      concentration ([Ca(2+)](i)) were determined in individual neocortical neurons by
      the Fluo-3/AM tracing method. The MTT assay demonstrated that MA has a dose
      dependent neurotoxicity in neuronal cultures. The addition of Rhy prior to the
      exposure to MA prevented neuronal death. Time course studies with the Fluo-3/AM
      probe showed that Rhy significantly decreased neuronal [Ca(2+)](i) which was
      elevated by the exposure to MA. Our results suggested that Rhy can protect the
      neuronal cultures against MA exposure and promptly attenuate intracellular
      calcium overload triggered by MA challenge. This is the first report
      demonstrating an inhibitory effect of Rhy against MA impairment in cultured
      neurons in vitro.

PMID- 22619689
TI  - Morinda citrifolia (Noni) Juice Augments Mammary Gland Differentiation and
      Reduces Mammary Tumor Growth in Mice Expressing the Unactivated c-erbB2
      Transgene.
AB  - Morinda citrifolia (noni) is reported to have many beneficial properties,
      including on immune, inflammatory, quality of life, and cancer endpoints, but
      little is known about its ability to prevent or treat breast cancer. To test its
      anticancer potential, the effects of Tahitian Noni Juice (TNJ) on mammary
      carcinogenesis were examined in MMTV-neu transgenic mice. Mammary tumor latency,
      incidence, multiplicity, and metastatic incidence were unaffected by TNJ
      treatment, which suggests that it would not increase or decrease breast cancer
      risk in women taking TNJ for its other benefits. However, noni may be useful to
      enhance treatment responses in women with existing HER2/neu breast cancer since
      TNJ resulted in significant reductions in tumor weight and volume and in longer
      tumor doubling times in mice. Remarkably, its ability to inhibit the growth of
      this aggressive form of cancer occurred with the mouse equivalent of a
      recommended dose for humans (<3 oz/day). A 30-day treatment with TNJ also induced
      significant changes in mammary secondary ductule branching and lobuloalveolar
      development, serum progesterone levels, and estrous cycling. Additional studies
      investigating TNJ-induced tumor growth suppression and modified reproductive
      responses are needed to characterize its potential as a CAM therapy for women
      with and without HER2(+) breast cancer.

PMID- 22619691
TI  - Chemical Composition and In Vitro Cytotoxic Activity of Essential Oil of Leaves
      of Malus domestica Growing in Western Himalaya (India).
AB  - Light pale-colored volatile oil was obtained from fresh leaves of Malus domestica
      tree, growing in Dhauladhar range of Himalaya (Himachal Pradesh, India), with
      characteristic eucalyptol dominant fragrance. The oil was found to be a complex
      mixture of mono-, sesqui-, di-terpenes, phenolics, and aliphatic hydrocarbons.
      Seventeen compounds accounting for nearly 95.3% of the oil were characterized
      with the help of capillary GC, GC-MS, and NMR. Major compounds of the oil were
      characterized as eucalyptol (43.7%), phytol (11.5%), alpha-farnesene (9.6%), and
      pentacosane (7.6%). Cytotoxicity of essential oil of leaves of M. domestica was
      evaluated by sulforhodamine B (SRB) assays. The essential oil of leaves of M.
      domestica, tested against three cancer cell lines, namely, C-6 (glioma cells),
      A549 (human lung carcinoma), CHOK1 (Chinese hamster ovary cells), and THP-1
      (human acute monocytic leukemia cell). The highest activity showed by essential
      oil on C-6 cell lines (98.2%) at concentration of 2000 MUg/ml compared to
      control. It is the first paper in literature to exploit the chemical composition
      and cytotoxic activity of leaves essential oil of M. domestica.

PMID- 22619692
TI  - Complementary and alternative medicine education for medical profession:
      systematic review.
AB  - Purpose. To help integrate traditional, complementary and alternative medicine
      (TCAM) into health systems, efforts are being made to educate biomedical doctors
      (BMD) and medical students on TCAM. We systematically evaluated the effect of
      TCAM education on BMD and medical students' attitude, knowledge, and behavior
      towards TCAM utilization and integration with biomedical medicine. Methods.
      Evaluative studies were identified from four databases. Methodological quality
      was assessed using the Medical Education Research Study Quality Instrument
      (MERSQI). Study outcomes were classified using Kirkpatrick's hierarchy. Results.
      3122 studies were identified and 12 studies of mediocre quality met inclusion
      criteria. Qualitative synthesis showed usage of diverse approaches including
      didactic, experiential learning, varying length, teacher background and intensity
      of exposure. More positive attitudes and improved knowledge after intervention
      were noted especially when teachers were BM trained. However, few studies
      assessed behavior change objectively. Finally, longer-term objective outcomes
      such as impact on patient care were not assessed. Conclusions. Lack of use of
      objective and reliable instruments preclude firm conclusion on the effect of TCAM
      education on study participants. However, positive changes, although mostly
      subjectively reported, were noted in most studies. Future evaluation should use
      validated or objective outcome assessments, and the value of using dual trained
      instructors.

PMID- 22619693
TI  - Technical Parameters for Laser Acupuncture to Elicit Peripheral and Central
      Effects: State-of-the-Art and Short Guidelines Based on Results from the Medical
      University of Graz, the German Academy of Acupuncture, and the Scientific
      Literature.
AB  - The scientific literature in the area of laser acupuncture is rather large;
      however, the actual mechanisms and effects have not yet been proven in detail.
      Since the early days of laser acupuncture, there are still many open questions
      concerning technical parameters of this innovative technique. In this paper, we
      report about the most important technical parameters (wavelength, output power,
      power density, energy density, dose range, and continuous or pulsed laser) for
      laser acupuncture and present quantitative results for optimal laser stimulation,
      which allow eliciting reproducible effects in the periphery and in the brain.
      There are several position statements on laser acupuncture and also several
      review articles in scientific literature concerning clinical effectiveness of
      laser acupuncture. For example, the Australian Medical Acupuncture College stated
      recently that "the optimal energy density for laser acupuncture and
      biostimulation, based on current clinical experience, is 4 J/cm(2)". However, our
      results of previous research studies and of this paper clearly show that dose
      must be adjusted according to the individual responses.

PMID- 22619694
TI  - Advances in the diagnosis and treatment of acute pulmonary embolism.
AB  - Over the past two decades, considerable progress in technology and clinical
      research methods have led to advances in the diagnosis, treatment and prevention
      of acute venous thromboembolism. Despite this, however, the diagnosis is still
      often missed and preventive methods are often ignored. Published guidelines are
      useful, but are limited by the existing evidence base so that controversies
      remain with regard to topics such as duration of anticoagulation, indications for
      placement and removal of inferior vena caval filters, and when and how to
      administer thrombolytic therapy. The morbidity and mortality of this disease
      remain high, particularly when undiagnosed. While preventive approaches remain
      crucial, the focus of this review is on the diagnostic and therapeutic approach
      to acute venous thromboembolism, with an emphasis on acute pulmonary embolism.

PMID- 22619695
TI  - Molecular beacons in diagnostics.
AB  - Recent technical advances have begun to realize the potential of molecular
      beacons to test for diverse infections in clinical diagnostic laboratories. These
      include the ability to test for, and quantify, multiple pathogens in the same
      clinical sample, and to detect antibiotic resistant strains within hours. The
      design principles of molecular beacons have also spawned a variety of allied
      technologies.

PMID- 22619698
TI  - Assessment of hybridization among wild and cultivated Vigna unguiculata
      subspecies revealed by arbitrarily primed polymerase chain reaction analysis.
AB  - BACKGROUND AND AIMS: Intra-species hybridization and incompletely homogenized
      ribosomal RNA repeat units have earlier been reported in 21 accessions of Vigna
      unguiculata from six subspecies using internal transcribed spacer (ITS) and 5S
      intergenic spacer (IGS) analyses. However, the relationships among these
      accessions were not clear from these analyses. We therefore assessed intra
      species hybridization in the same set of accessions. METHODOLOGY: Arbitrarily
      primed polymerase chain reaction (AP-PCR) analysis was carried out using 12
      primers. The PCR products were resolved on agarose gels and the DNA fragments
      were scored manually. Genetic relationships were inferred by TREECON software
      using unweighted paired group method with arithmetic averages (UPGMA) cluster
      analysis evaluated by bootstrapping and compared with previous analyses based on
      ITS and 5S IGS. PRINCIPAL RESULTS: A total of 202 (86 %) fragments were found to
      be polymorphic and used for generating a genetic distance matrix. Twenty-one V.
      unguiculata accessions were grouped into three main clusters. The cultivated
      subspecies (var. unguiculata) and most of its wild progenitors (var. spontanea)
      were placed in cluster I along with ssp. pubescens and ssp. stenophylla. Whereas
      var. spontanea were grouped with ssp. alba and ssp. tenuis accessions in cluster
      II, ssp. alba and ssp. baoulensis were included in cluster III. Close affinities
      of ssp. unguiculata, ssp. alba and ssp. tenuis suggested inter-subspecies
      hybridization. CONCLUSIONS: Multi-locus AP-PCR analysis reveals that intra
      species hybridization is prevalent among V. unguiculata subspecies and suggests
      that grouping of accessions from two different subspecies is not solely due to
      the similarity in the ITS and 5S IGS regions but also due to other regions of the
      genome.

PMID- 22619697
TI  - Desferrioxamine attenuates doxorubicin-induced acute cardiotoxicity through TFG
      beta/Smad p53 pathway in rat model.
AB  - Interaction of doxorubicin DOX with iron and the consequent generation of
      reactive oxygen species (ROS) is a major player in DOX-induced cardiomyopathy.
      Accordingly, this study has been initiated to investigate the preventive effect
      of the iron chelator, desferrioxamine (DFX), against DOX-induced acute
      cardiotoxicity in rats. Male Wistar albino rats were divided into four groups and
      were injected intraperitoneally (I.P.) with normal saline, a single dose of DOX
      (15 mg/kg), a single dose of DFX (250 mg/kg) and a combined treatment with DFX
      (250 mg/kg) 30 min prior to a single dose of DOX, (15 mg/kg). A single dose of
      DOX significantly increased mRNA expression of TGF-beta, Smad2, Smad4, CDKN2A and
      p53 and significantly decreased Samd7 and Mdm2 mRNA expression levels.
      Administration of DFX prior to DOX resulted in a complete reversal of DOX-induced
      alteration in cardiac enzymes and gene expression to normal levels. Data from
      this study suggest that (1) DOX induces its acute cardiotoxicity secondary to
      increasing genes expression of TGF-beta/Smad pathway. (2) DOX increases apoptosis
      through upregulation of CDKN2A and p53 and downregulation of Mdm2 gene
      expression. (3) The preventive effect of DFX against DOX-induced cardiotoxicity
      is mediated via the TGF-beta1/Smad pathway.

PMID- 22619699
TI  - Immunity to protozoan parasites.

PMID- 22619700
TI  - Optical coherence tomography in ophthalmology.

PMID- 22619696
TI  - The bad, the good, and the ugly about oxidative stress.
AB  - Alzheimer's disease (AD), Parkinson's disease (PD), and cancer (e.g., leukemia)
      are the most devastating disorders affecting millions of people worldwide. Except
      for some kind of cancers, no effective and/or definitive therapeutic treatment
      aimed to reduce or to retard the clinic and pathologic symptoms induced by AD and
      PD is presently available. Therefore, it is urgently needed to understand the
      molecular basis of these disorders. Since oxidative stress (OS) is an important
      etiologic factor of the pathologic process of AD, PD, and cancer, understanding
      how intracellular signaling pathways respond to OS will have a significant
      implication in the therapy of these diseases. Here, we propose a model of minimal
      completeness of cell death signaling induced by OS as a mechanistic explanation
      of neuronal and cancer cell demise. This mechanism might provide the basis for
      therapeutic design strategies. Finally, we will attempt to associate PD, cancer,
      and OS. This paper critically analyzes the evidence that support the "oxidative
      stress model" in neurodegeneration and cancer.

PMID- 22619701
TI  - Health status and patient satisfaction after corneal graft: results from the
      corneal transplant epidemiological study.
AB  - Purpose. To evaluate effects of corneal transplantation on the health-related
      quality of life and patients' satisfaction. Methods. Patients scheduled for
      elective penetrating or anterior lamellar keratoplasty completed by telephone
      interview the SF-12 Health Survey, before and one year after surgery, and a 6
      item questionnaire on the satisfaction for graft outcomes. Results. The two
      questionnaires were answered by 1,223 patients. Transplantation did not influence
      the PCS-12 in males (ES = -0.01) and had a negative effect in females (ES = 
      0.18). Both sexes improved their MCS-12 (ES = 0.18 and 0.23, resp.). The majority
      of patients (83.1%) were satisfied by the outcome of the graft. Conclusions. This
      is the first report on the use of the SF-12 and one of the few that assess
      quality of life in patients after corneal transplantation. We showed that
      grafting improves patients' health-related quality of life results of patients,
      influencing mental health (i.e., psychological attitude, social interaction, and
      emotions) with minor effects on physical health (limitation, pain, and vitality).

PMID- 22619702
TI  - Risk factors for endophthalmitis and retinal detachment with retained intraocular
      foreign bodies.
AB  - Purpose. To analyze risk factors for endophthalmitis and retinal detachment (RD)
      in patients with retained intraocular foreign bodies (IOFBs). Design. A
      retrospective, interventional, consecutive case series. Participants. All
      patients treated at Bascom Palmer Eye Institute for traumatic IOFBs between 1999
      and 2008. Methods. Analysis of visual outcome, mechanism of injury, management,
      and postoperative course. Results. 108 eyes with IOFBs were identified.
      Endophthalmitis occurred in 7 eyes (6.4%) at presentation, and risk was higher
      with vegetable matter exposure (P = 0.003). All eyes with posterior segment IOFBs
      received intravitreal antibiotics and there were no cases of endophthalmitis
      after initial management. RD was identified in 6 of 108 eyes (5.5%) at
      presentation. Risk factors were entry more than 5 mm behind the limbus (P <
      0.001) and posterior segment IOFB (P = 0.028). Postoperative RD occurred in 11 of
      102 eyes (10.7%). Risk factors for postoperative RD were preoperative
      endophthalmitis (P = 0.001), posterior segment IOFB (P = 0.008), and retinal
      impact sites (P = 0.028). Conclusions. Risk factors for endophthalmitis included
      vegetable matter exposure and delay to initial management. Risk factors for RD
      were posterior entry site, posterior segment IOFB, endophthalmitis, and retinal
      impact sites. No eyes developed endophthalmitis after presentation.

PMID- 22619703
TI  - Fast Food Consumption, Quality of Diet, and Obesity among Isfahanian Adolescent
      Girls.
AB  - Background and Objective. Few data are available linking fast food intake to diet
      quality in developing countries. This study was conducted to determine the
      association between fast food consumption and diet quality as well as obesity
      among Isfahani girls. Methods. This cross-sectional study was done among 140
      Iranian adolescents selected by the use of systematic cluster random sampling.
      Dietary intakes were assessed using a validated food frequency questionnaire.
      Diet quality was defined based on energy density and nutrient adequacy ratios
      (NARs). Results. Individuals in the highest quartile of fast food intake had
      significantly lower NARs for vitamin B(1) (P = 0.008), phosphorus (P = 0.0250),
      selenium (P < 0.001) and vitamin B(2) (P = 0.012) compared with those in the
      lowest quartile. Those in top quartile of fast food intake consumed more energy
      dense diets than those in the bottom quartile (P = 0.022). High intakes of fast
      foods were significantly associated with overweight (top quartile: 40% versus
      bottom quartile: 0%, P = 0.0001) and obesity (11.4% versus 2.9%, P = 0.0001).
      Conclusion. Fast food consumption is associated with poor diet quality and high
      prevalence of overweight and obesity among Isfahani adolescents. Prospective data
      are required to confirm these findings.

PMID- 22619704
TI  - Influence of running and walking on hormonal regulators of appetite in women.
AB  - Nine female runners and ten walkers completed a 60 min moderate-intensity (70%
      VO(2)max) run or walk, or 60 min rest in counterbalanced order. Plasma
      concentrations of the orexogenic peptide ghrelin, anorexogenic peptides peptide
      YY (PYY), glucagon-like peptide-1 (GLP-1), and appetite ratings were measured at
      30 min interval for 120 min, followed by a free-choice meal. Both orexogenic and
      anorexogenic peptides were elevated after running, but no changes were observed
      after walking. Relative energy intake (adjusted for cost of exercise/rest) was
      negative in the meal following running (-194 +/- 206 kcal) versus walking (41 +/-
      196 kcal) (P = 0.015), although both were suppressed (P < 0.05) compared to rest
      (299 +/- 308 and 284 +/- 121 kcal, resp.). The average rate of change in PYY and
      GLP-1 over time predicted appetite in runners, but only the change in GLP-1
      predicted hunger (P = 0.05) in walkers. Results provide evidence that exercise
      induced alterations in appetite are likely driven by complex changes in appetite
      regulating hormones rather than change in a single gut peptide.

PMID- 22619705
TI  - Randomized controlled trial of the effectiveness of genetic counseling and a
      distance, computer-based, lifestyle intervention program for adult offspring of
      patients with type 2 diabetes: background, study protocol, and baseline patient
      characteristics.
AB  - Relatives of type 2 diabetic patients are at a high risk of developing type 2
      diabetes and should be regarded as target of intervention for diabetes
      prevention. However, it is usually hard to motivate them to implement preventive
      lifestyle changes, because of lack of opportunity to take advises from medical
      professionals, inadequate risk perception, and low priority for preventive
      behavior. Prevention strategy for them therefore should be highly acceptable and
      suited for them. The parallel, three-group trial is now being conducted to
      investigate the effects of genetic counseling and/or a computerized behavioral
      program on the prevention of type 2 diabetes in that population. The preventive
      strategies used in this study could provide a novel solution to the numbers of
      genetically high-risk individuals, if found to be effective. The objective of
      this paper is to describe the background, protocol, and baseline patient
      characteristics of the trial.

PMID- 22619706
TI  - Interleukin 28B Gene Polymorphism and Association with Chronic Hepatitis C
      Therapy Results in Latvia.
AB  - Introduction. With the standard treatment of chronic hepatitis C, sustained
      virological response (SVR) can be achieved only in half of all patients.
      Interleukin-28B appears to be involved in the control of HCV infection, and the
      genetic polymorphism of the encoding IL-28B gene may determine the efficacy of
      clearance of HCV. The aim of this paper was to detect IL-28B gene polymorphism in
      Latvia and to analyze therapy results. This is the first study on IL-28B gene
      polymorphism in Latvia. Material and Methods. There were 159 chronic viral
      hepatitis C patients included in the study. In order to detect IL-28B gene
      polymorphism, we used molecular biology techniques and methods: classical DNA
      separation, amplification by PCR, and standard sequencing. Genotype was defined
      as CC, CT, TC, or TT type. 142 patients were treated with the standard of care
      treatment. Results were analyzed according to IL-28B polymorphism. Results. There
      were 53 patients (33%) with CC genotype, 84 patients (53%) with CT/TC genotype,
      and 22 patients (14%) with TT genotype. 34 patients (74%) in CC genotype subgroup
      achieved SVR versus 50 patients (52%) in non-CC subgroups. In patients with
      genotype 1, SVR was achieved in 16 patients (84%) in CC subgroup versus 30
      patients (47.6%) in non-CC subgroups, P = 0.007. Conclusions. The most common
      genotype of IL28B in Latvia is CT/TC, with an incidence of 53%. Patients with CC
      genotype achieved SVR more often than CT or TT subgroups. IL28B gene polymorphism
      therefore is a strong predictor of treatment result.

PMID- 22619707
TI  - Appreciation of a Child's Journey: Implementation of a Cardiac Action Research
      Project.
AB  - The aim of this paper is to provide an overview of the phases of the action
      research process involved in developing, implementing, and evaluating the Heart
      Beads program. The aim of the project is to enrich the hospital experience of
      children with cardiac conditions. Heart Beads involves children receiving unique
      beads specific to each cardiac treatment, procedure or event in recognition of
      their experiences, and endurance. An action research approach, involving a
      partnership between clinicians and researchers and emphasising the involvement of
      patients and their families, was used to guide the Heart Beads program. The
      project followed the five phases of action research: identification,
      investigation, program development, implementation, and evaluation. Heart Beads
      began as a small project which continues to grow in popularity and significance
      with children at a tertiary paediatric hospital in Sydney, Australia. The program
      is now being implemented nationwide with the vision that all Australian children
      hospitalised with cardiac conditions can benefit from Heart Beads.

PMID- 22619708
TI  - Infusing oral health care into nursing curriculum: addressing preventive health
      in aging and disability.
AB  - Access to oral health care is essential for promoting and maintaining overall
      health and well-being, yet oral health disparities exist among vulnerable and
      underserved populations. While nurses make up the largest portion of the health
      care work force, educational preparation to address oral health needs of elders
      and persons with disabilities is limited across nursing curricula. This
      descriptive study reports on the interdisciplinary development, implementation,
      and testing of an oral health module that was included and infused into a
      graduate nursing curriculum in a three-phase plan. Phase 1 includes evaluation of
      a lecture presented to eight gerontological nurse practitioner (GNP) students.
      Phase 2 includes evaluation of GNP students' perceptions of learning, skills, and
      confidence following a one-time 8-hour practicum infused into 80 required
      practicum hours. The evaluation data show promise in preparing nurse practitioner
      students to assess and address preventive oral health needs of persons aging with
      disabilities such that further infusion and inclusion in a course for nurse
      practitioners across five specialties will implemented and tested in Phase 3.

PMID- 22619709
TI  - Comparison of biomarkers in blood and saliva in healthy adults.
AB  - Researchers measure biomarkers as a reflection of patient health status or
      intervention outcomes. While blood is generally regarded as the best body fluid
      for evaluation of systemic processes, substitution of saliva samples for blood
      would be less invasive and more convenient. The concentration of specific
      biomarkers may differ between blood and saliva. The objective of this study was
      to compare multiple biomarkers (27 cytokines) in plasma samples, passive drool
      saliva samples, and filter paper saliva samples in 50 healthy adults. Demographic
      data and three samples were obtained from each subject: saliva collected on
      filter paper over 1 minute, saliva collected by passive drool over 30 seconds,
      and venous blood (3 mL) collected by venipuncture. Cytokines were assayed using
      Bio-Rad multiplex suspension array technology. Descriptive statistics and
      pairwise correlations were used for data analysis. The sample was 52% male and
      74% white. Mean age was 26 (range = 19-63 years, sd = 9.7). The most consistent
      and highest correlations were between the passive drool and filter paper saliva
      samples, although relationships were dependent on the specific biomarker.
      Correlations were not robust enough to support substitution of one collection
      method for another. There was little correlation between the plasma and passive
      drool saliva samples. Caution should be used in substituting saliva for blood,
      and relationships differ by biomarker.

PMID- 22619710
TI  - Single-port laparoscopic surgery for inflammatory bowel disease.
AB  - Background. Single Port Laparoscopic Surgery (SPLS) is being increasingly
      employed in colorectal surgery for benign and malignant diseases. The particular
      role for SPLS in inflammatory bowel disease (IBD) has not been determined yet. In
      this review article we summarize technical aspects and short term results of SPLS
      resections in patients with Crohn's disease or ulcerative colitis. Methods. A
      systematic review of the literature until January 2012 was performed.
      Publications were assessed for operative techniques, equipment, surgical results,
      hospital stay, and readmissions. Results. 34 articles, published between 2010 and
      2012, were identified reporting on 301 patients with IBD that underwent surgical
      treatment in SPLS technique. Surgical procedures included ileocolic resections,
      sigmoid resections, colectomies with end ileostomy or ileorectal anastomosis, and
      restorative proctocolectomies with ileum-pouch reconstruction. There was a wide
      variety in the surgical technique and the employed equipment. The overall
      complication profile was similar to reports on standard laparoscopic surgery in
      IBD. Conclusions. In experienced hands, single port laparoscopic surgery appears
      to be feasible and safe for the surgical treatment of selected patients with IBD.
      However, evidence from prospective randomized trials is required in order to
      clarify whether there is a further benefit apart from the avoidance of additional
      trocar incisions.

PMID- 22619711
TI  - Antineuropathic and antinociceptive drugs combination in patients with chronic
      low back pain: a systematic review.
AB  - Purpose. Chronic low back pain (LBP) is often characterized by both nociceptive
      and neuropathic components. While various monotherapies have been reported of
      only limited efficacy, combining drugs with different mechanisms of action and
      targets appears a rational approach. Aim of this systematic review is to assess
      the efficacy and safety of different combined pharmacological treatments,
      compared to monotherapy or placebo, for the pharmacological treatment of chronic
      LBP. Methods. Published papers, written or abstracted in English from 1990
      through 2011, comparing combined pharmacological treatments of chronic LBP to
      monotherapy or placebo were reviewed. Results. Six articles met the inclusion
      criteria. Pregabalin combined with celecoxib or opioids was shown to be more
      effective than either monotherapy. Oxycodone-paracetamol versus previous
      treatments and tramadol-paracetamol versus placebo were also reported as
      effective, while morphine-nortriptyline did not show any benefit over any single
      agent. Conclusions. In spite of theoretical advantages of combined
      pharmacological treatments of chronic LBP, clinical studies are remarkably few.
      Available data show that combined therapy, including antinociceptive and
      antineuropathic agents is more effective than monotherapy, with similar side
      effects.

PMID- 22619714
TI  - The role of bacteria in the pathogenesis of ulcerative colitis.
AB  - Factors implicated in the pathophysiology of ulcerative colitis (UC) are an
      abnormal immune response, defect in intestinal epithelial barrier function, and
      gut microbiota. Currently, it is unclear whether specific bacterial strains are
      responsible for the induction of intestinal inflammation, but increased bacterial
      tissue invasion has been described in affected UC patients. Further, a
      quantitative and qualitative microbial imbalance in UC, defined as dysbiosis, has
      been characterized by an increase in Rhodococcus spp., Shigella spp., and
      Escherichia spp., but a decrease in certain Bacteroides spp.. More specifically,
      Campylobacter spp., Enterobacteriae, and enterohepatic Helicobacter were more
      prevalent in tissue sample from UC patients subjected to molecular detection
      methods, but not controls. In addition, serologic testing identified Fusobacterim
      varium as a potential contributor to the intestinal inflammation in UC.
      Interestingly, in-situ hybridization studies have shown anti-inflammatory
      Lactobacillus spp. and Pediococcus spp. were absent in samples from subjects
      affected by UC. Therefore, dysbiosis is a factor in the pathogenesis of UC.

PMID- 22619715
TI  - Abnormalities of the ventilatory equivalent for carbon dioxide in patients with
      chronic heart failure.
AB  - Introduction. The relation between minute ventilation (VE) and carbon dioxide
      production (VCO(2)) can be characterised by the instantaneous ratio of
      ventilation to carbon dioxide production, the ventilatory equivalent for CO(2)
      (VEqCO(2)). We hypothesised that the time taken to achieve the lowest VEqCO(2)
      (time to VEqCO2 nadir) may be a prognostic marker in patients with chronic heart
      failure (CHF). Methods. Patients and healthy controls underwent a symptom
      limited, cardiopulmonary exercise test (CPET) on a treadmill to volitional
      exhaustion. Results. 423 patients with CHF (mean age 63 +/- 12 years; 80% males)
      and 78 healthy controls (62% males; age 61 +/- 11 years) were recruited. Time to
      VEqCO2 nadir was shorter in patients than controls (327 +/- 204 s versus 514 +/-
      187 s; P = 0.0001). Univariable predictors of all-cause mortality included peak
      oxygen uptake (X(2) = 53.0), VEqCO(2) nadir (X(2) = 47.9), and time to VEqCO(2)
      nadir (X(2) = 24.0). In an adjusted Cox multivariable proportional hazards model,
      peak oxygen uptake (X(2) = 16.7) and VEqCO(2) nadir (X(2) = 17.9) were the most
      significant independent predictors of all-cause mortality. Conclusion. The time
      to VEqCO(2) nadir was shorter in patients with CHF than in normal subjects and
      was a predictor of subsequent mortality.

PMID- 22619716
TI  - Glioblastoma multiforme.

PMID- 22619713
TI  - Potential for Cell-Transplant Therapy with Human Neuronal Precursors to Treat
      Neuropathic Pain in Models of PNS and CNS Injury: Comparison of hNT2.17 and
      hNT2.19 Cell Lines.
AB  - Effective treatment of sensory neuropathies in peripheral neuropathies and spinal
      cord injury (SCI) is one of the most difficult problems in modern clinical
      practice. Cell therapy to release antinociceptive agents near the injured spinal
      cord is a logical next step in the development of treatment modalities. But few
      clinical trials, especially for chronic pain, have tested the potential of
      transplant of cells to treat chronic pain. Cell lines derived from the human
      neuronal NT2 cell line parentage, the hNT2.17 and hNT2.19 lines, which synthesize
      and release the neurotransmitters gamma-aminobutyric acid (GABA) and serotonin
      (5HT), respectively, have been used to evaluate the potential of cell-based
      release of antinociceptive agents near the lumbar dorsal (horn) spinal sensory
      cell centers to relieve neuropathic pain after PNS (partial nerve and diabetes
      related injury) and CNS (spinal cord injury) damage in rat models. Both cell
      lines transplants potently and permanently reverse behavioral hypersensitivity
      without inducing tumors or other complications after grafting. Functioning as
      cellular minipumps for antinociception, human neuronal precursors, like these NT2
      derived cell lines, would likely provide a useful adjuvant or replacement for
      current pharmacological treatments for neuropathic pain.

PMID- 22619712
TI  - Drug management of visceral pain: concepts from basic research.
AB  - Visceral pain is experienced by 40% of the population, and 28% of cancer patients
      suffer from pain arising from intra- abdominal metastasis or from treatment.
      Neuroanatomy of visceral nociception and neurotransmitters, receptors, and ion
      channels that modulate visceral pain are qualitatively or quantitatively
      different from those that modulate somatic and neuropathic pain. Visceral pain
      should be recognized as distinct pain phenotype. TRPV1, Na 1.8, and ASIC3 ion
      channels and peripheral kappa opioid receptors are important mediators of
      visceral pain. Mu agonists, gabapentinoids, and GABAB agonists reduce pain by
      binding to central receptors and channels. Combinations of analgesics and
      adjuvants in animal models have supra-additive antinociception and should be
      considered in clinical trials. This paper will discuss the neuroanatomy,
      receptors, ion channels, and neurotransmitters important to visceral pain and
      provide a basic science rationale for analgesic trials and management.

PMID- 22619717
TI  - Physiological changes associated with aging and immobility.

PMID- 22619718
TI  - Aging in place in late life: theory, methodology, and intervention.

PMID- 22619719
TI  - New Strategies to Fight against Sarcopenia at Old Age.

PMID- 22619720
TI  - Blockade of electron transport at the onset of reperfusion decreases cardiac
      injury in aged hearts by protecting the inner mitochondrial membrane.
AB  - Myocardial injury is increased in the aged heart following ischemia-reperfusion
      (ISC-REP) compared to adult hearts. Intervention at REP with ischemic
      postconditioning decreases injury in the adult heart by attenuating mitochondrial
      driven cell injury. Unfortunately, postconditioning is ineffective in aged
      hearts. Blockade of electron transport at the onset of REP with the reversible
      inhibitor amobarbital (AMO) decreases injury in adult hearts. We tested if AMO
      treatment at REP protects the aged heart via preservation of mitochondrial
      integrity. Buffer-perfused elderly Fischer 344 24 mo. rat hearts underwent 25 min
      global ISC and 30 min REP. AMO (2.5 mM) or vehicle was given for 3 min at the
      onset of REP. Subsarcolemmal (SSM) and interfibrillar (IFM) mitochondria were
      isolated after REP. Oxidative phosphorylation (OXPHOS) and mitochondrial inner
      membrane potential were measured. AMO treatment at REP decreased cardiac injury.
      Compared to untreated ISC-REP, AMO improved inner membrane potential in SSM and
      IFM during REP, indicating preserved inner membrane integrity. Thus, direct
      pharmacologic modulation of electron transport at REP protects mitochondria and
      decreases cardiac injury in the aged heart, even when signaling-induced pathways
      of postconditioning that are upstream of mitochondria are ineffective.

PMID- 22619721
TI  - Congenital anomalies and termination of pregnancy in Iran.
AB  - The aim of this study was to document some epidemiological features of
      termination of pregnancy for birth defects in Iran. We studied 603 pregnant women
      who were diagnosed/recommended for the termination of pregnancy as having a fetus
      with some types of birth defect(s). Most women (87.2 percent) had at least one
      ultrasound examination. The proportion of other screening tests including
      amniocentesis and genetic tests were 2.8 and 4.6 percent, respectively. Of 603
      women, 201 terminated the pregnancy giving a prevalence rate of 33.3 percent (CI
      95%: 29.6-37.6). The remaining 402 subjects were unable to get the permission for
      abortion because of untimely diagnosis/application for termination (20th week of
      pregnancy and/or later). Forty-eight percent of termination of pregnancies was
      performed before the 18th week of pregnancy. Neural tube defects, limb
      deformation, hydrops fetalis, hydrocephaly, and chromosomal anomalies including
      Down syndrome accounted proportionally for about 65 percent of defects eligible
      for abortion in the region. Although the rate of termination of pregnancy for
      birth defects is acceptable at the current situation in the country, more efforts
      should still be made to convince the community authorities to give more
      possibility and ease for the termination of pregnancy for congenital anomalies.

PMID- 22619722
TI  - Uterine healing after therapeutic intrauterine administration of TachoSil
      (hemostatic fleece) in cesarean section with postpartum hemorrhage caused by
      placenta previa.
AB  - BACKGROUND: Application of hemostatic fleece (TachoSil) directly onto the
      bleeding surfaces of the lower uterine segment has been used to obtain hemostasis
      during cesarean section caused by placenta previa. METHODS: Eleven of 15 patients
      treated with TachoSil for excessive postpartum haemorrhage due to placenta previa
      were enrolled. An evaluation of the cesarean section scar by transvaginal
      ultrasound, the uterine cavity and endometrium by hysteroscopy, and the
      endometrium by biopsy were made. The main outcome measures were intrauterine
      adhesions, recovery of endometrium at the site of TachoSil application, visible
      remnants of TachoSil, and scar healing. RESULTS: Eight patients had small
      remnants of TachoSil in the uterine cavity together with signs of resorption. All
      had a normal endometrial mucosa, and none had adhesions in the uterine cavity.
      All cesarean section scars were healed without defects. CONCLUSION: TachoSil did
      not seem to impair healing of the endometrium or scar formation in the uterus
      after intrauterine application. Resorption of TachoSil seems to progress
      individually. Intrauterine treatment with TachoSil is a valuable supplement to
      the traditional treatment of post partum haemorrhage and may help retain
      reproductive capability. This is a small study, and it will require more studies
      to confirm the reproducibility.

PMID- 22619723
TI  - Validity and reproducibility of the measurements obtained using the flexicurve
      instrument to evaluate the angles of thoracic and lumbar curvatures of the spine
      in the sagittal plane.
AB  - Objective. to verify the validity and reproducibility of using the flexicurve to
      measure the angles of the thoracic and lumbar curvatures. Method. 47 subjects
      were evaluated by: (1) palpation and marking of the spinous processes using lead
      markers, (2) using X-rays in the sagittal plane to measure the Cobb angles, (3)
      molding the flexicurve to the spine, and (4) drawing the contour of the
      flexicurve onto graph paper. The angle of curvature was determined with the
      flexicurve based on a 3rd order polynomial. Results. No differences were found
      between the Cobb angles and the angles obtained using the flexicurve in thoracic
      and lumbar curvatures (P > 0.05). Correlations were strong and significant for
      the thoracic (r = 0.72, P < 0.01) and lumbar (r = 0.60, P < 0.01) curvatures.
      Excellent and significant correlations were found for both the intraevaluator and
      interevaluator measurements. Conclusion. The results show that there is no
      significant difference between the values obtained using the flexicurve and those
      obtained using the X-ray procedure and that there is a strong correlation between
      the two methods. This, together with the excellent level of inter- and
      intraevaluator reproducibility justifies its recommendation for use in clinical
      practice.

PMID- 22619724
TI  - A system utilizing metal hydride actuators to achieve passive motion of toe
      joints for prevention of pressure ulcers: a pilot study.
AB  - This paper describes the influence of human toe movement on blood flow and the
      design of a toe joint passive motion system for preventing pressure ulcers.
      First, we measured lower extremity blood flow in the foot during active and
      passive motion of the toe to facilitate the design of new rehabilitation
      equipment. Also, the flexion and extension angles and the force of the toe joints
      were measured to determine appropriate specifications for the system. Increases
      in blood flow were observed at the external malleolus during movement. Flexion
      and extension angles and the force of the toe joints were found to differ
      significantly among participants. It is shown that a toe joint passive motion
      system can be effective in preventing pressure ulcers. On the basis of these
      results, a device using alloys of metal hydride (MH) as an actuator that is
      suitable for the system to initiate toe motion, was developed.

PMID- 22619726
TI  - Averting Behavior Framework for Perceived Risk of Yersinia enterocolitica
      Infections.
AB  - The focus of this research is to present a theoretical model of averting actions
      that households take to avoid exposure to Yersinia enterocolitica in contaminated
      food. The cost of illness approach only takes into account the value of a cure,
      while the averting behavior approach can estimate the value of preventing the
      illness. The household, rather than the individual, is the unit of analysis in
      this model, where one household member is primarily responsible for procuring
      uncontaminated food for their family. Since children are particularly susceptible
      and live with parents who are primary decision makers for sustenance, the
      designated household head makes the choices that are investigated in this paper.
      This model uses constrained optimization to characterize activities that may
      offer protection from exposure to Yersinia enterocolitica contaminated food. A
      representative household decision maker is assumed to allocate family resources
      to maximize utility of an altruistic parent, an assumption used in most research
      involving economics of the family.

PMID- 22619725
TI  - Combination drug delivery approaches in metastatic breast cancer.
AB  - Disseminated metastatic breast cancer needs aggressive treatment due to its
      reduced response to anticancer treatment and hence low survival and quality of
      life. Although in theory a combination drug therapy has advantages over single
      agent therapy, no appreciable survival enhancement is generally reported whereas
      increased toxicity is frequently seen in combination treatment especially in
      chemotherapy. Currently used combination treatments in metastatic breast cancer
      will be discussed with their challenges leading to the introduction of novel
      combination anticancer drug delivery systems that aim to overcome these
      challenges. Widely studied drug delivery systems such as liposomes, dendrimers,
      polymeric nanoparticles, and water-soluble polymers can concurrently carry
      multiple anticancer drugs in one platform. These carriers can provide improved
      target specificity achieved by passive and/or active targeting mechanisms.

PMID- 22619727
TI  - The current role of androgen deprivation in patients undergoing dose-escalated
      external beam radiation therapy for clinically localized prostate cancer.
AB  - Purpose. To review existing literature on the role of androgen deprivation
      therapy (ADT) with dose escalated radiation therapy. Methods and Materials. A
      PubMed search was undertaken to identify relevant articles. Results. Multiple
      recent studies were identified examining the role of ADT in the current era of
      radiation dose-escalation. Among the reviewed studies, varying radiation doses
      and techniques, ADT regimens, and patient selection criteria were utilized.
      Conflicting results were reported, with some studies demonstrating a benefit of
      delivering a higher radiation dose with ADT. Other studies failed to show
      significant benefits with the addition of ADT to dose-escalated RT. Conclusions.
      The benefit of adding ADT to dose-escalated RT is still uncertain. Prospective
      randomized trials, several of which are ongoing, are necessary to more adequately
      examine this issue. In the interim, physicians and patients should continue to
      utilize the existing data to weigh the risks and benefits of each approach to
      therapy.

PMID- 22619728
TI  - Qualification of staff, organization of services, and management of pregnant
      women in rural settings: the case of diema and kayes districts (mali).
AB  - In Mali, a poor sub-Saharan country, maternity referral systems were implemented
      to combat the still-high rates of maternal mortality. This qualitative study was
      aimed at understanding the relationships between the qualification of staff in
      community health centres, the organization of services, and the management of
      pregnant women in the maternity referral system in Kayes, a rural region of Mali.
      Physicians who managed CHCs actively or passively modified work organization, the
      level of technology, their obstetric skills, and staffing. They also created a
      competitive environment and developed relationships of trust with patients and
      with the district health centre. These findings are helpful in orienting decision
      making for better personnel management.

PMID- 22619729
TI  - To compare the methods of pregnancy termination for fetal abnormality in the
      first and second trimesters.
AB  - Fetal abnormality is a major cause of termination of pregnancy and preservation
      of the fetus is important for confirmation of the diagnosis. Various regimes have
      been reported for termination of pregnancy for fetal abnormality in the first and
      the second trimesters. In this paper, we compare those regimes that allow
      preservation of the fetus, in terms of the efficacy in expulsion of the fetus,
      the factors and the side effects.

PMID- 22619731
TI  - Efficacy of various antidiabetic agents as add-on treatments to metformin in type
      2 diabetes mellitus: systematic review and meta-analysis.
AB  - Background and Aim. Diabetes mellitus is a chronic disease that has a great
      impact on patients and society. Metformin monotherapy is capable of maintaining a
      target glycemic control only for a short term. The aim of this study was to
      determine the efficacy of combination therapy of metformin with any antidiabetic
      agents in type 2 diabetes mellitus (T2DM) patients. Methods. Reports of
      randomized controlled trials (RCTs) of combination therapy of metformin with
      various antidiabetic agents in T2DM failing metformin alone were identified.
      Results. Eight studies were identified in our paper. Thiazolidinediones (TZDs)
      were as effective as dipeptidyl peptidase IV inhibitors (DPP IV inhs) in reducing
      HbA1c value (pooled mean difference -0.03%; 95% CI -0.16 to 0.10%). In comparison
      between TZDs and sulphonylureas (SUs), TZDs reduced fasting plasma insulin (FPI)
      more effectively than SUs (pool mean difference -5.72 MUU/mL; 95% CI -8.21 to 
      3.22 MUU/mL, P < 0.00001), but no significant differences were detected in the
      effects on HbA1c and fasting plasma glucose (FPG) (pooled mean difference -2.19
      mg/dL; 95% CI -11.32 to 6.94 mg/dL, P = 0.64). Conclusions. Our study showed that
      TZDs reduced FPG better than did DPP IV inhs and decreased FPI more than did SUs.

PMID- 22619732
TI  - Computerized morphometric analysis of human femoral articular cartilage.
AB  - Objective. Articular cartilage shows changes with age that are considered to be
      the most important factors in the development and progression of osteoarthritis.
      The studies on age changes in articular cartilage have been traditionally based
      on individual observations but this approach is limited by its subjectivity and
      bias, yielding considerable variability. So the present study was conducted to
      observe various age related changes in morphology of femoral articular cartilage
      using computerized morphometric analysis. Design. The articular cartilage
      specimens were divided into two groups according to age: group 1 (n = 16) below
      40 years (16-40 years) and group 2 (n = 12) above 40 years (41-86 years) of age.
      5 MUm thick paraffin sections were stained with H&E and analyzed using Image Pro
      Express image analysis software for quantitative analysis of articular cartilage.
      Various parameters, that is, total thickness of the cartilage, area of lacunae in
      each zone, area of subchondral cavities, and number of chondrocytes per 10,000
      MUm(2) area in each zone were measured. Results. Significant difference with age
      was found in the total thickness and area of lacunae in zone 3. Conclusions. Not
      much difference is observed in articular cartilage morphology with age. So ageing
      is not the only risk factor in development of osteoarthritis.

PMID- 22619733
TI  - Burnout among Nurses in a Nigerian General Hospital: Prevalence and Associated
      Factors.
AB  - Objective. To evaluate the prevalence and associated factors of burnout among
      nurses in a Nigerian general hospital. Methods. A total sampling method was
      utilized. Measurements. Burnout was evaluated using the Maslach Burnout
      Inventory; GHQ-12 was used to determine the presence of psychiatric morbidity.
      Results. A high level of burnout was identified in 39.1% of the respondents in
      the area of emotional exhaustion (EE), 29.2% in the area of depersonalization and
      40.0% in the area of reduced personal accomplishment. Multivariate analysis
      showed that doctor/nurse conflict (OR = 3.1, 95% CI: 1.9-6.3), inadequate nursing
      personnel (OR = 2.6, 95% CI: 1.5-5.1), and too frequent night duties (OR = 3.1,
      95% CI: 1.7-5.6) were predictors of burnout in the area of EE, doctor/nurse
      conflict (OR = 3.4, 95% CI: 2.2-7.6) and too frequent night duties (OR = 2.4, 95%
      CI 1.5-4.8) in the area of D, high nursing hierarchy (OR = 2.7, 95% CI: 1.5-4.8),
      poor wages (OR = 2.9, 95% CI: 1.6-5,6), and too frequent night duties (OR = 2.3,
      95% CI: 2.3-4.5) in the area of RPA. Conclusions. Prevalence of burnout among
      these nurses was high. The government therefore needs to look into factors that
      will enhance nurses' recruitment and retention for effective health care delivery
      system.

PMID- 22619730
TI  - Role of Gut-Related Peptides and Other Hormones in the Amelioration of Type 2
      Diabetes after Roux-en-Y Gastric Bypass Surgery.
AB  - Bariatric surgery is currently the most effective and durable therapy for
      obesity. Roux-en-Y gastric bypass surgery, the most commonly performed procedure
      worldwide, causes substantial weight loss and improvement in several
      comorbidities associated with obesity, especially type 2 diabetes. Several
      mechanisms are proposed to explain the improvement in glucose metabolism after
      RYGB surgery: the caloric restriction and weight loss per se, the improvement in
      insulin resistance and beta cell function, and finally the alterations in the
      various gastrointestinal hormones and adipokines that have been shown to play an
      important role in glucose homeostasis. However, the timing, exact changes of
      these hormones, and the relative importance of these changes in the metabolic
      improvement postbariatric surgery remain to be further clarified. This paper
      reviews the various changes post-RYGB in adipokines and gut peptides in subjects
      with T2D.

PMID- 22619734
TI  - Role of vitamin d in Parkinson's disease.
AB  - Parkinson's disease (PD) is the second most common form of neurodegeneration in
      the elderly population. Clinically, it is characterized by tremor, rigidity,
      slowness of movement, and postural imbalance. A significant association between
      low serum vitamin D and PD has been demonstrated, suggesting that elevated
      vitamin D levels might provide protection against PD. Genetic studies have helped
      identify a number of proteins linking vitamin D to PD pathology, including the
      major histocompatibility complex (MHC) class II, the vitamin D receptor (VDR),
      cytochrome P450 2D6 (CYP2D6), chromosome 22, the renin-angiotensin system (RAS),
      heme oxygenase-1 (HO-1), poly(ADP-ribose) polymerase-1 gene (PARP-1),
      neurotrophic factor (NTF), and Sp1 transcription factor. Vitamin D has also been
      implicated in PD through its effects on L-type voltage-sensitive calcium channels
      (L-VSCC), nerve growth factor (NGF), matrix metalloproteinases (MMPs),
      prostaglandins (PGs) and cyclooxygenase-2 (COX-2), reactive oxygen species (ROS),
      and nitric oxide synthase (NOS). A growing body of evidence suggests that vitamin
      D supplementation may be beneficial for PD patients. Among the different forms of
      vitamin D, calcitriol (1,25-dihydroxyvitamin D(3)) is best indicated for PD,
      because it is a highly active vitamin D(3) metabolite with an appropriate
      receptor in the central nervous system (CNS).

PMID- 22619735
TI  - Metastatic squamous cell carcinoma of the anus: time for a shift in the treatment
      paradigm?
AB  - Anal cancers are rare tumours; however, the incidence is increasing in both men
      and women. Changing trends in sexual behaviour, smoking, and infection with the
      human papillomavirus are thought to be responsible for the increase. Patients
      with metastatic disease have a poor prognosis, with 5-year median overall
      survival rates of 10% in men and 20% in women. The standard systemic treatment of
      metastatic disease remains cisplatin and 5-fluorouracil, and aside from several
      non-randomised small phase II trials there has been no real progress over the
      past two decades. Based on the efficacy of cetuximab in squamous cell carcinomas
      from other primary sites, there appears to be clinical rationale for evaluation
      of anti-epidermal growth factor inhibitors in anal squamous cell carcinoma. In
      order to facilitate research and implement more effective treatment strategies
      international collaboration in clinical trials incorporating tissue collection
      for biomarkers is essential.

PMID- 22619736
TI  - Time to be SHY? Some comments on sleep and synaptic homeostasis.
AB  - Sleep must serve an essential, universal function, one that offsets the risk of
      being disconnected from the environment. The synaptic homeostasis hypothesis
      (SHY) is an attempt to identify this essential function. Its core claim is that
      sleep is needed to reestablish synaptic homeostasis, which is challenged by the
      remarkable plasticity of the brain. In other words, sleep is "the price we pay
      for plasticity." In this issue, M. G. Frank reviewed several aspects of the
      hypothesis and raised several issues. The comments below provide a brief summary
      of the motivations underlying SHY and clarify that SHY is a hypothesis not about
      specific mechanisms, but about a universal, essential function of sleep. This
      function is the preservation of synaptic homeostasis in the face of a systematic
      bias toward a net increase in synaptic strength--a challenge that is posed by
      learning during adult wake, and by massive synaptogenesis during development.

PMID- 22619737
TI  - Plasticity and mTOR: towards restoration of impaired synaptic plasticity in mTOR
      related neurogenetic disorders.
AB  - OBJECTIVE: To review the recent literature on the clinical features, genetic
      mutations, neurobiology associated with dysregulation of mTOR (mammalian target
      of rapamycin), and clinical trials for tuberous sclerosis complex (TSC),
      neurofibromatosis-1 (NF1) and fragile X syndrome (FXS), and phosphatase and
      tensin homolog hamartoma syndromes (PTHS), which are neurogenetic disorders
      associated with abnormalities in synaptic plasticity and mTOR signaling. METHODS:
      Pubmed and Clinicaltrials.gov were searched using specific search strategies.
      RESULTS/CONCLUSIONS: Although traditionally thought of as irreversible disorders,
      significant scientific progress has been made in both humans and preclinical
      models to understand how pathologic features of these neurogenetic disorders can
      be reduced or reversed. This paper revealed significant similarities among the
      conditions. Not only do they share features of impaired synaptic plasticity and
      dysregulation of mTOR, but they also share clinical features--autism,
      intellectual disability, cutaneous lesions, and tumors. Although scientific
      advances towards discovery of effective treatment in some disorders have outpaced
      others, progress in understanding the signaling pathways that connect the entire
      group indicates that the lesser known disorders will become treatable as well.

PMID- 22619738
TI  - Gene therapy for Parkinson's disease.
AB  - Current pharmacological and surgical treatments for Parkinson's disease offer
      symptomatic improvements to those suffering from this incurable degenerative
      neurological disorder, but none of these has convincingly shown effects on
      disease progression. Novel approaches based on gene therapy have several
      potential advantages over conventional treatment modalities. These could be used
      to provide more consistent dopamine supplementation, potentially providing
      superior symptomatic relief with fewer side effects. More radically, gene therapy
      could be used to correct the imbalances in basal ganglia circuitry associated
      with the symptoms of Parkinson's disease, or to preserve or restore dopaminergic
      neurons lost during the disease process itself. The latter neuroprotective
      approach is the most exciting, as it could theoretically be disease modifying
      rather than simply symptom alleviating. Gene therapy agents using these
      approaches are currently making the transition from the laboratory to the
      bedside. This paper summarises the theoretical approaches to gene therapy for
      Parkinson's disease and the findings of clinical trials in this rapidly changing
      field.

PMID- 22619740
TI  - Quantitative mechanical properties of the relaxed biceps and triceps brachii
      muscles in patients with subacute stroke: a reliability study of the myoton-3
      myometer.
AB  - Objective. Test-retest reliability of the myotonometer was investigated in
      patients with subacute stroke. Methods. Twelve patients with substroke (3 to 9
      months poststroke) were examined in standardized testing position twice, 60
      minutes apart, with the Myoton-3 myometer to measure tone, elasticity, and
      stiffness of relaxed bilateral biceps and triceps brachii muscles. Intrarater
      reliability of muscle properties was determined using intraclass correlation
      coefficient (ICC), the standard error of measurement (SEM), and the minimal
      detectable change (MDC). Results. Intrarater reliability of muscle properties of
      bilateral biceps and triceps brachii muscles were good (ICCs = 0.79-0.96) except
      for unaffected biceps tone (ICC = 0.72). The SEM and MDC of bilateral biceps and
      triceps brachii muscles indicated small measurement error (SEM% <10%, MDC% <25%).
      Conclusion. The Myoton-3 myometer is a reliable tool for quantifying muscle tone,
      elasticity, and stiffness of the biceps and triceps brachii in patients with
      subacute stroke.

PMID- 22619739
TI  - Clinicopathological features and management of cancers in lynch syndrome.
AB  - Lynch syndrome (LS) is characterized by an autosomal dominant inheritance of the
      early onset of colorectal cancer (CRC) and endometrial cancer, as well as
      increased risk for several other cancers including gastric, urinary tract,
      ovarian, small bowel, biliary tract, and brain tumors. The syndrome is due to a
      mutation in one of the four DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, or
      PMS2. The majority of LS patients and families can now be identified, and the
      underlying mutation detected using genetic diagnostics. Regular surveillance for
      CRC and endometrial cancer has proved beneficial for mutation carriers. However,
      screening for other tumors is also recommended even though experiences in the
      screening of these tumors is limited. Prophylactic colectomy, prophylactic
      hysterectomy, and bilateral salpingo-oophorectomy may be reasonable options for
      selected patients with LS. This paper describes the features and management of
      LS.

PMID- 22619741
TI  - The Neurorehabilitation Training Toolkit (NTT): A Novel Worldwide Accessible
      Motor Training Approach for At-Home Rehabilitation after Stroke.
AB  - After stroke, enduring rehabilitation is required for maximum recovery, and
      ideally throughout life to prevent functional deterioration. Hence we developed a
      new concept for at-home low-cost motor rehabilitation, the NTT, an Internet-based
      interactive system for upper-limb rehabilitation. In this paper we present the
      NTT design concepts, its implementation and a proof of concept study with 10
      healthy participants. The NTT brings together concepts of optimal learning,
      engagement, and storytelling to deliver a personalized training to its users. In
      this study we evaluate the feasibility of NTT as a tool capable of automatically
      assessing and adapting to its user. This is achieved by means of a psychometric
      study where we show that the NTT is able to assess movement kinematics-movement
      smoothness, range of motion, arm displacement and arm coordination-in healthy
      users. Subsequently, a modeling approach is presented to understand how the
      measured movement kinematics relate to training parameters, and how these can be
      modified to adapt the training to meet the needs of patients. Finally, an
      adaptive algorithm for the personalization of training considering motivational
      and performance aspects is proposed. In the next phase we will deploy and
      evaluate the NTT with stroke patients at their homes.

PMID- 22619742
TI  - Analysis of In Vitro Effects of Sex Steroids on Lymphocyte Responsiveness in
      Murrah Buffaloes (Bubalus bubalis).
AB  - Present study was carried out on forty four apparently healthy Murrah buffaloes
      of different age groups of both sexes to investigate the effects of sex steroids
      on cell mediated immunity in vitro. Estrogen inhibited proliferation in mitogen
      stimulated lymphocytes from prepubertal but not post pubertal buffaloes of either
      sex. Estrogen at 100 pg/mL concentration stimulating the proliferation
      significantly (P < 0.05). in all groups and had higher stimulatory effect in
      lymphocytes from day 10 than day 0 of estrous cycle. Progesterone inhibited
      lymphocyte proliferation, and inhibition was directly related to the dose, in all
      groups of either sex. Testosterone did not inhibit proliferation at any dose
      level and did not show any consistent and lucid effects on lymphocyte
      proliferation. Present study revealed that buffalo lymphocytes produce
      appreciable amounts of NO in culture system after treatment with estradiol.
      Significantly high levels of NO in culture supernatant were found in prepubertal
      buffalo calves and least in post pubertal buffaloes, which had an inverse
      relation with lymphocyte proliferation in presence of estradiol. NO in culture
      supernatant was high at the lowest dose of progesterone which was proportional to
      the lymphocyte proliferation when treated with progesterone. No significant
      difference in NO culture supernatant was observed between different
      concentrations of testosterone treatment.

PMID- 22619743
TI  - DNA Typing of Mycobacterium bovis Isolates from Badgers (Meles meles) Culled from
      Areas in Ireland with Different Levels of Tuberculosis Prevalence.
AB  - Badgers (Meles meles) have been implicated in the transmission of Mycobacterium
      bovis infection to cattle in Ireland and UK. Recent studies in Ireland have shown
      that although the disease is endemic in badgers, the prevalence of disease is not
      uniform throughout the country and can vary among subpopulations. The extent to
      which the prevalence levels in badgers impact on the prevalence in cattle is not
      known. Previously, DNA fingerprinting has shown that M. bovis strain types are
      shared between badgers and cattle, and that there are a large number of strain
      types circulating in the two species. In this study we have carried out
      spoligotyping and variable number tandem repeat (VNTR) analysis of M. bovis
      isolates from two groups of badgers, representing a wide geographic area, with
      different tuberculosis prevalence levels. The results of the typing show that
      there is no geographic clustering of strain types associated with prevalence.
      However, two VNTR profiles were identified that appear to be associated with high
      and low-prevalence M. bovis infection levels, respectively. In addition,
      spoligotyping and VNTR analysis has provided evidence, for the first time, of
      multiple infections of individual badgers with different M. bovis strains.

PMID- 22619744
TI  - RP-HPLC Method Development and Its Validation for Quantitative Determination of
      Rimonabant in Human Plasma.
AB  - A simple, accurate, and precise HPLC method was developed and validated for
      determination of rimonabant in human plasma. Following liquid-liquid extraction,
      chromatographic separation was accomplished using C18 column with mobile phase
      consisting of acetonitrile : water (90 : 10, v/v), drug was detected at 260 nm
      using UVdetector. The LOD and LOQ were 3.0 and 10.0 MUg/L, respectively. The
      method is linear in the interval 50.0-1000.0 MUg/L. The average extraction
      recovery of drug from plasma was found to be 92.2%. The percent CV of the method
      was found to be less than 10.8%, and accuracy was found between 94.5 and 106.7%.
      The assay may be applied to a pharmacokinetic and bioequivalence study of
      rimonabant.

PMID- 22619745
TI  - Searching surface orientation of microscopic objects for accurate 3D shape
      recovery.
AB  - In this article, we propose a new shape from focus (SFF) method to estimate 3D
      shape of microscopic objects using surface orientation cue of each object patch.
      Most of the SFF algorithms compute the focus value of a pixel from the
      information of neighboring pixels lying on the same image frame based on an
      assumption that the small object patch corresponding to the small neighborhood of
      a pixel is a plane parallel to the focal plane. However, this assumption fails in
      the optics with limited depth of field where the neighboring pixels of an image
      have different degree of focus. To overcome this problem, we try to search the
      surface orientation of the small object patch corresponding to each pixel in the
      image sequence. Searching of the surface orientation is done indirectly by
      principal component analysis. Then, the focus value of each pixel is computed
      from the neighboring pixels lying on the surface perpendicular to the
      corresponding surface orientation. Experimental results on synthetic and real
      microscopic objects show that the proposed method produces more accurate 3D shape
      in comparison to the existing techniques.

PMID- 22619746
TI  - Kidney injury and cell therapy: Preclinical study.
AB  - The aim of this study is to show histological and immunofluorescence analysis of
      renal parenchyma of agoutis affected by gentamicin-induced renal disease after
      the infusion of bone marrow mononuclear cells (BMMC) stained with Hoechst(r).
      Nine agouti's males were divided into three groups: Test group (TG): renal
      disease by gentamicin induced (n = 3), cell therapy group (CTG): renal disease by
      gentamicin induced and BMMC infusion (n = 3), and control group (CG): nonrenal
      disease and BMMC infusion (n = 3). TG and CTG were submitted to the protocol of
      renal disease induction using weekly application of gentamicin sulfate for 4
      months. CG and CTG received a 1 * 108 BMMC stained with Hoechst and were
      euthanized for kidney examination 21 days after BMMC injection and samples were
      collected for histology and immunofluorescence analysis. Histological analysis
      demonstrated typical interstitial lesions in kidney similarly to human disease,
      as tubular necrosis, glomerular destruction, atrophy tubular, fibrotic areas, and
      collagen deposition. We conclude that histological analysis suggest a positive
      application of agouti's as a model for a gentamicin inducing of kidney disease,
      beyond the immunofluorescence analysis suggest a significant migration of BMMC to
      sites of renal injury in CTG.

PMID- 22619747
TI  - Development of a high-throughput DNA microarray for drug-resistant  gene
      detection  and its preliminary application.
AB  - Most bacteria are resistant to a wide variety of antibiotics and other drugs,
      which decrease the effectiveness of clinical drug therapies. The present study
      developed a high-throughput DNA microarray for drug-resistant gene detection. A
      total of 115 specific oligonuclieotide probes with lengths of 42 nt to 45 nt and
      comparable Tm values were selected from 17 categories of drug-resistant genes in
      the National Center for Biotechnology Information database and were chemically
      synthesized. The entire bacterial DNA was extracted, randomly amplified, and
      labeled using Cy3-dCTP. The hybridization conditions of the microarray test were
      optimized to improve sensitivity and specificity. The drug-resistant genes were
      detected and genotyped using microarray analysis after hydration at 42 degrees C
      for 4h with 2* hybridization solution. The microarray test sensitivity was
      20ng/MUL DNA. The performance of the microarray was validated using reference
      strains and clinical isolates. The results were consistent with direct DNA
      sequence analysis and drug susceptibility tests. The developed DNA microarray
      could be used to detect and screen drug-resistant bacteria rapidly and
      simultaneously. Thus, the present study could be helpful in effectively using
      antibiotics and controlling infectious diseases.

PMID- 22619748
TI  - Schmallenberg virus confirmed in south-east England.

PMID- 22619749
TI  - Vasomotion does inhibit mass exchange between axisymmetric blood vessels and
      tissue.
AB  - Vasomotion, the name given to the physiological phenomenon whereby blood vessel
      walls exhibit rhythmic oscillations in diameter, is a complex process and very
      poorly understood. It has been proposed as a mechanism for protecting tissue when
      perfusion levels are reduced, since it has experimentally been shown to occur
      more frequently under such conditions. However, no quantitative evidence yet
      exists for whether the oscillation of the wall actually has any effect on mass
      transport to tissue. In our previous work, it was shown that the presence of non
      linearities in the governing equation could result in a significant change in
      time-averaged mass transport to tissue: however, it was not possible, due to the
      limitations of the model, to determine whether time-averaged mass transport
      increased or decreased. This model is extended in this paper through coupling of
      the one-dimensional axisymmetric mass transport equations in tissue and blood to
      quantify the effects of vasomotion on mass transport to tissue. The results show
      that over a wide parameter range, surrounding those values calculated from
      experimental data, vasomotion does inhibit mass transport to tissue in a one
      dimensional axisymmetric blood vessel by an amount that is predominantly
      dependent upon the amplitude of oscillation and that increases rapidly at larger
      oscillation amplitudes.

PMID- 22619751
TI  - Does natural selection favour the Rescorla-Wagner rule?
AB  - A fundamental question relating to animal behaviour is how animals learn; in
      particular, how they come to associate stimuli with rewards. Numerous empirical
      findings can be explained by assuming that animals use some mechanism similar to
      the Rescorla-Wagner learning rule, which is a relatively simple and highly
      general method of updating the associative strength between different stimuli.
      However, the Rescorla-Wagner rule is often not optimal, which raises the question
      of why a rule with such properties should have evolved. We consider the evolution
      of learning rules in a simple environment where there exists an optimal rule of
      similar complexity to the Rescorla-Wagner rule. We show that because the Rescorla
      Wagner rule is less sensitive to changes in its parameters than the optimal rule,
      there is a wider range of parameter values over which the rule structure is
      initially viable. Consequently, the Rescorla-Wagner rule can be favoured by
      natural selection, ahead of other rules which are more accurate.

PMID- 22619750
TI  - Quantification of degeneracy in biological systems for characterization of
      functional interactions between modules.
AB  - There is an evolutionary advantage in having multiple components with overlapping
      functionality (i.e degeneracy) in organisms. While theoretical considerations of
      degeneracy have been well established in neural networks using information
      theory, the same concepts have not been developed for differential systems, which
      form the basis of many biochemical reaction network descriptions in systems
      biology. Here we establish mathematical definitions of degeneracy, complexity and
      robustness that allow for the quantification of these properties in a system. By
      exciting a dynamical system with noise, the mutual information associated with a
      selected observable output and the interacting subspaces of input components can
      be used to define both complexity and degeneracy. The calculation of degeneracy
      in a biological network is a useful metric for evaluating features such as the
      sensitivity of a biological network to environmental evolutionary pressure. Using
      a two-receptor signal transduction network, we find that redundant components
      will not yield high degeneracy whereas compensatory mechanisms established by
      pathway crosstalk will. This form of analysis permits interrogation of large
      scale differential systems for non-identical, functionally equivalent features
      that have evolved to maintain homeostasis during disruption of individual
      components.

PMID- 22619752
TI  - Leishmania infantum nicotinamidase is required for late-stage development in its
      natural sand fly vector, Phlebotomus perniciosus.
AB  - Leishmania infantum nicotinamidase, encoded by the Lipnc1 gene, converts
      nicotinamide into nicotinicacid to ensure Nicotinamide-Adenine-Dinucleotide
      (NAD+) biosynthesis. We were curious to explore the role of this enzyme during L.
      infantum development in its natural sand fly vector, Phlebotomus perniciosus
      (Diptera, Phlebotominae), using null mutants with a deleted Lipnc1 gene. The null
      mutants developed as well as the wild type L. infantum at the early time points
      post their ingestion within the bloodmeal. In contrast, once the blood meal
      digestion was completed, the null mutants were unable to develop further and
      establish late-stage infections. Data highlight the importance of the
      nicotinamide degradation pathway for Leishmania development in sand flies. They
      indicate that the endogenous nicotinamidase is essential for Leishmania
      development in the sand fly after the blood meal has been digested and the
      remnants defecated.

PMID- 22619753
TI  - Heart disease in women II: diagnosis and treatment.

PMID- 22619754
TI  - Detection of a quantitative trait locus associated with resistance to Ascaris
      suum infection in pigs.
AB  - Helminths almost invariably have an over-dispersed distribution in the host
      population. Human and animal studies have provided evidence suggesting that a
      large part of this variation is due to host genetic factors. Recently, the
      heritability for roundworm (Ascaris suum) infection levels in pigs was estimated
      to be 0.45. We used single nucleotide polymorphism markers to perform a whole
      genome scan on 195 pigs experimentally infected with A. suum. A putative
      quantitative trait locus for worm burden on chromosome 4 covering 2.5 Mbp was
      identified by measured genotype analysis, although none of the SNPs reached
      genome-wide significance. To validate the putative quantitative trait locus, we
      genotyped two of the SNPs within the region in unrelated, informative animals
      exposed to experimental or natural infections and from which we had worm counts
      and/or faecal egg counts; the validation studies showed that one of the SNPs
      (TXNIP) was associated with total worm burden (P < 0.001) and adult worm burden(P
      < 0.0001), whereas the other SNP (ARNT) was associated with adult worm burden (P
      < 0.025) in these populations. We were thus able to confirm the existence of the
      quantitative trait locus on chromosome 4.This is to our knowledge the first
      report of a quantitative trait locus associated with helminth burden in pigs.

PMID- 22619757
TI  - The American College of Cardiology sets  the pace: it's a close call between the
      catheter  and the computer.

PMID- 22619756
TI  - Extra-glycosomal localisation of Trypanosoma brucei hexokinase 2.
AB  - The majority of the glycolytic enzymes in the African trypanosome are
      compartmentalised within peroxisome-like organelles, the glycosomes. Polypeptides
      harbouring peroxisomal targeting sequences (PTS type 1 or 2) are targeted to
      these organelles. This targeting is essential to parasite viability, as
      compartmentalisation of glycolytic enzymes prevents unregulated ATP-dependent
      phosphorylation of intermediate metabolites. Here, we report the surprising extra
      glycosomal localisation of a PTS-2 bearing trypanosomal hexokinase, TbHK2. In
      bloodstream form parasites, the protein localises to both glycosomes and to the
      flagellum. Evidence for this includes fractionation and immunofluorescence
      studies using antisera generated against the authentic protein as well as
      detection of epitope-tagged recombinant versions of the protein. In the insect
      stage parasite, distribution is different, with the polypeptide localised to
      glycosomes and proximal to the basal bodies. The function of the extra-glycosomal
      protein remains unclear. While its association with the basal body suggests that
      it may have a role in locomotion in the insect stage parasite, no detectable
      defect in directional motility or velocity of cell movement were observed for
      TbHK2-deficient cells, suggesting that the protein may have a different function
      in the cell.

PMID- 22619755
TI  - Common pathways for receptor-mediated ingestion of Escherichia coli and LDL
      cholesterol by Entamoeba histolytica regulated in part by transmembrane kinase
      39.
AB  - The single-celled parasite, Entamoeba histolytica, is an enteric pathogen that
      ingests bacteria and host cells. Inhibition of phagocytosis renders the parasite
      avirulent. The ligand/receptor interactions that allow E. histolytica to
      phagocytose are not well understood. We hypothesised that E. histolytica
      trophozoites might accomplish ingestion through the utilisation of a scavenger
      receptor for cholesterol. Here we show that acetylated low density lipoprotein
      cholesterol was phagocytosed by amoebae via receptor mediated mechanisms.
      Acetylated low density lipoprotein cholesterol competitively inhibited by 31 +/-
      1.3% (P < 0.005) the ingestion of Escherichia coli, but not erythrocytes and
      Jurkat T lymphocytes, suggesting a partially redundant phagocytic pathway for E.
      coli and cholesterol. Inducible expression ofa signalling-dead dominant-negative
      version of E. histolytica transmembrane kinase 39 inhibited ingestion of E. coli
      by 55 +/- 3% (P < 0.005) but not LDL particles. We concluded that ingestion of E.
      coli was regulated by TMK39 and partially shared the acetylated low density
      lipoprotein cholesterol uptake pathway.

PMID- 22619758
TI  - Turkey's response to CardioPulse Survey.

PMID- 22619759
TI  - The need for meaningful reform in aged care.

PMID- 22619760
TI  - Commonwealth Nurses Conference.

PMID- 22619761
TI  - Promises and possibilities from the QNU Health Forum.

PMID- 22619762
TI  - Means testing of government rebates for private health insurance.

PMID- 22619763
TI  - 25,000 Kenyan nurses sacked after demanding their agreed pay rise.

PMID- 22619764
TI  - EB8 and election promises: where do we go from here?

PMID- 22619765
TI  - QNU Legal Plus experience on your side.

PMID- 22619766
TI  - PI insurance and NMBA requirements: your questions answered.

PMID- 22619767
TI  - Get your shots: nurses and midwives targeted in flu campaign.

PMID- 22619768
TI  - Nurse practitioners in the GP setting.

PMID- 22619769
TI  - Using the business planning framework.

PMID- 22619770
TI  - The sustainable growth rate: the elephant in the room of deficit reduction.
AB  - The sustainable growth rate (SGR) is a formulaic approach intended to restrain
      the growth of Medicare spending on physician services. Permanently replacing the
      SGR will cost $300 billion to $400 billion. Ten years of congressional overrides
      have contributed to higher Medicare spending on physician services. The absence
      of a replacement for the SGR leaves the federal government with a significant
      budget deficit exposure.

PMID- 22619771
TI  - [I. The role of microRNA for musculoskeletal cancer].

PMID- 22619772
TI  - [II. Possibility of molecular targeting therapy for musculoskeletal cancer].

PMID- 22619773
TI  - [III. The role of chemotherapy for soft tissue neoplasm].

PMID- 22619774
TI  - Colonising motherhood: Evangelical social reformers and Koorie women in Victoria,
      Australia, 1880s to the early 1900s.

PMID- 22619775
TI  - Explaining high health care spending in the United States: an international
      comparison of supply, utilization, prices, and quality.
AB  - This analysis uses data from the Organization for Economic Cooperation and
      Development and other sources to compare health care spending, supply,
      utilization, prices, and quality in 13 industrialized countries: Australia,
      Canada, Denmark, France, Germany, Japan, the Netherlands, New Zealand, Norway,
      Sweden, Switzerland, the United Kingdom, and the United States. The U.S. spends
      far more on health care than any other country. However this high spending cannot
      be attributed to higher income, an older population, or greater supply or
      utilization of hospitals and doctors. Instead, the findings suggest the higher
      spending is more likely due to higher prices and perhaps more readily accessible
      technology and greater obesity. Health care quality in the U.S. varies and is not
      notably superior to the far less expensive systems in the other study countries.
      Of the countries studied, Japan has the lowest health spending, which it achieves
      primarily through aggressive price regulation.

PMID- 22619776
TI  - Courting men: mothers, magistrates and welfare in the Australian colonies.

PMID- 22619777
TI  - Courtship, sex and money: the economics of courtesan houses in nineteenth- and
      twentieth-century Shanghai.

PMID- 22619778
TI  - Creating a (gendered?) military identity: the Women's Auxiliary Air Force in
      Great Britain in the Second World War.

PMID- 22619779
TI  - "How are they at home?" Community, state and servicemen's wives in England, 1939
      45.

PMID- 22619780
TI  - "I am directed to remind you of your duty to your family": public surveillance of
      mothering in Victoria, Australia, 1920-40.

PMID- 22619781
TI  - "Jolly good reading" for girls: discourses of library work and femininity in
      career novels.

PMID- 22619782
TI  - Lavinia Seabrooke, gender and state formation in late nineteenth-century south
      Australia.

PMID- 22619783
TI  - Mothering feminism/mothering feminists: Ray Strachey and "The Cause".

PMID- 22619784
TI  - Opportunities and limitations: the New Woman in Third Reich cinema.

PMID- 22619785
TI  - Physical purity feminism and state medicine in late nineteenth-century England.

PMID- 22619786
TI  - Private loss, public mourning: motherhood, memory and grief in Australia during
      the inter-war years.

PMID- 22619787
TI  - Sex education debates and the modest mother in Australia, 1890s to the 1930s.

PMID- 22619788
TI  - Some reflections on gender, sociology and women's history.

PMID- 22619789
TI  - The creation of "motherhood" and women's responses in Britain and France, 1750
      1914.

PMID- 22619790
TI  - "The door is not locked": recollections of my life.

PMID- 22619791
TI  - The lady of Tower Bridge: Sybil Campbell, England's first woman judge.

PMID- 22619792
TI  - The perils of Mrs. Pooter: satire, modernity and motherhood in the lower middle
      class in England, 1870-1920.

PMID- 22619793
TI  - The political and the personal: the radicalism of Sophia Chichester and Georgiana
      Fletcher Welch.

PMID- 22619794
TI  - The womanly garb of Queen Victoria's early motherhood, 1840-42.

PMID- 22619795
TI  - Willing women and the rise of convents in nineteenth-century England.

PMID- 22619796
TI  - Wives and mistresses in eighteenth-century Scotland.

PMID- 22619797
TI  - Carnival in Bolivia: devils dancing for the virgin.

PMID- 22619798
TI  - [Evaluation on stability of internal controls in human cardiac muscle by real
      time RT-PCR during early postmortem interval].
AB  - OBJECTIVE: To explore the stability of internal controls in human cardiac muscle
      by real-time RT-PCR during early postmortem interval (PMI) in order to find the
      most stable marker. METHODS: Ten individuals with similar environmental
      conditions (the average store temperature: 25 degrees C) and different PMI
      ranging from 4.3 to 22.3 h were selected. Total RNA was extracted from each
      sample and six commonly internal controls were used including beta-actin, GAPDH,
      B2M, U6, 18S rRNA and HSA-miR-1, and the expression was detected in cardiac
      muscle by real-time RT-PCR. The expression stability of internal controls was
      evaluated using genormPLUS software during early PMI. The internal control with
      the most stability was selected. The relationship between the most stable marker
      and its expression level affected by some other parameters such as age, gender
      and cause of death was also analyzed. RESULTS: The U6 showed the most stable
      expression during early PMI in cardiac muscle, and its expression level was not
      affected by those parameters including age, gender and cause of death (P > 0.05).
      CONCLUSION: U6 may be a valuable internal control for the study of relationship
      between PMI determination and degradation of nucleic acid in human cardiac muscle
      by real-time RT-PCR.

PMID- 22619799
TI  - [Distribution of human enterovirus 71 in brainstem of infants with brain stem
      encephalitis and infection mechanism].
AB  - OBJECTIVE: To explore the mechanism that how human enterovirus 71 (EV71) invades
      the brainstem and how intercellular adhesion molecules-1 (ICAM-1) participates by
      analyzing the expression and distribution of human EV71, and ICAM-1 in brainstem
      of infants with brain stem encephalitis. METHODS: Twenty-two brainstem of infants
      with brain stem encephalitis were collected as the experimental group and 10
      brainstems of fatal congenital heart disease were selected as the control group.
      The sections with perivascular cuffings were selected to observe EV71-VP1
      expression by immunohistochemistry method and ICAM-1 expression was detected for
      the sections with EV71-VP1 positive expression. The staining image analysis and
      statistics analysis were performed. The experiment and control groups were
      compared. RESULTS: (1) EV71-VP1 positive cells in the experimental group were
      mainly astrocytes in brainstem with nigger-brown particles, and the control group
      was negative. (2) ICAM-1 positive cells showed nigger-brown. The expression in
      inflammatory cells (around blood vessels of brain stem and in glial nodules) and
      gliocytes increased. The results showed statistical difference comparing with
      control group (P < 0.05). CONCLUSION: The brainstem encephalitis can be used to
      diagnose fatal EV71 infection in infants. EV71 can invade the brainstem via
      hematogenous route. ICAM-1 may play an important role in the pathogenic process.

PMID- 22619801
TI  - [Establishment of skin scald model in mice].
AB  - OBJECTIVE: To establish the model of skin scald in mice for the study of skin
      thermal injuries. METHODS: After anaesthetization mice were scalded in a 1 cm
      diameter circle area on the central dorsum by boiling water at contact times: 10s
      or 25s. The mice were sacrificed at 1, 3, 5, 7 and 10 days after scald. The skin
      samples were collected and analyzed by gross and histopathological examinations.
      RESULTS: Deep II degree thermal injury involving full-thickness skin was observed
      in the 10s scald group. III degree thermal injury involving full-thickness skin
      and the dorsal skeletal muscle was observed in the 25 s scald group. CONCLUSION:
      A mouse skin scald model is established which is stable and can be used on the
      skin thermal injury in future research.

PMID- 22619800
TI  - [Estimation of postmortem interval by detecting thickness of cornea using
      ultrasonic method].
AB  - OBJECTIVE: To explore the postmortem changes of cornea thickness measured by
      ultrasonic pachymetry. METHODS: Eleven rabbits were randomly divided into two
      groups: one group with intact corneal epithelium and another group without intact
      corneal epithelium. In the later group, the corneal epithelium of the rabbit was
      scraped using mechanical elimination method. The corneal thickness was monitored
      continuously by ultrasonic pachymetry at several postmortem interval points in
      rabbits of the two groups. The changes of corneal thickness and postmortem
      interval were explored by relative regression analysis. RESULTS: The thickness of
      the cornea showed a strong non-linear correlation with the postmortem interval in
      the group with intact corneal epithelium. The group with intact corneal
      epithelium showed the correlation coefficient 0.922 and the group without intact
      corneal epithelium showed the correlation coefficient 0.822, respectively.
      CONCLUSION: The corneal thickness measured by ultrasonic pachymetry shows a
      potential value for estimating early postmortem interval. The intact corneal
      epithelium is a crucial factor for the measurement of cornea thickness by
      ultrasonic pachymetry.

PMID- 22619802
TI  - [Comparisons among different reference values of nerve conduction velocity in
      forensic appraisal].
AB  - OBJECTIVE: To provide the evidences for the choice of normal reference value of
      nerve conduction velocity (NCV) in clinical forensic appraisal. METHODS: One
      hundred and fourteen cases with normal peripheral nerve and 155 cases with
      injured peripheral nerve were collected. The NCV of homonymous nerves in two
      limbs were detected. In the normal cases, the NCV of the left limbs were used as
      the normal reference values. The NCV of the right limbs were compared with that
      of left limbs, the commendatory normal reference values from Beijing Xiehe
      Hospital and Shanghai Huashan Hospital. In the injured cases, the results of NCV
      in injuried limbs were compared with the results of healthy limbs and the
      reference values from Beijing Xiehe Hospital and Shanghai Huashan Hospital.
      RESULTS: In the normal group, there was no statistical difference between the
      left and right limbs in NCV results of homonymous nerve (P > 0.05). The false
      positive rates (FPR) were 0, 11.4% and 5.2% for three choices normal reference
      respectively. The false negative rates (FNR) were 0, 9.7% and 12.3% for three
      choices normal reference in injuried group. Thee false negative cases were all
      slight nerve injury. CONCLUSION: The reference value of self-control method could
      decrease the FPR of normal cases and FNR of injured cases. In clinical forensic
      appraisal of peripheral nerve, the nerve condition study results from healthy
      homonymous nerve should be regarded as the reference value at first, supplemented
      by reference values from clinical labs.

PMID- 22619803
TI  - [Comparisons among three frequency-specific auditory evoked potentials in normal
      hearing adults].
AB  - OBJECTIVE: To provide supports for the application of auditory evoked potential
      (AEP) in the evaluation of behavioral threshold, by studying the difference and
      relevance between the pure tone audiometry (PTA) and three frequency-specific
      auditory evoked potentials, including 40 Hz auditory event related potentials (40
      Hz AERP), tone burst auditory brainstem response (Tb-ABR) and auditory steady
      state response (ASSR). METHODS: Three frequency-specific AEP and PTA thresholds
      were recorded at speech frequency (0.5, 1, 2, 4 kHz) from thirty-four adults with
      normal hearing (68 ears). Then, the relationship between the AEP thresholds and
      PTA thresholds were analyzed respectively. RESULTS: There were good correlations
      between three frequency-specific AEP thresholds and PTA thresholds at speech
      frequency. However, the difference of thresholds between each frequency-specific
      AEP and PTA was not same. The difference of thresholds were the smallest and the
      relevance were the best between 40 Hz AERP and PTA at 0.5 kHz, and between ASSR
      and PTA at 2, 4 kHz. At 1 kHz, there were not statistical difference between
      ASSR, 40 Hz AERP and PTA, while the relevance of 40 Hz AERP was better than ASSR.
      CONCLUSION: Different methods should be chosen to assess the objective behavioral
      thresholds at different frequency.

PMID- 22619804
TI  - [Algorithms of likelihood ratio for discriminating full sibling from half
      sibling].
AB  - OBJECTIVE: To derive the formulae for likelihood ratio calculation in
      discriminating full sibling from half sibling with single-parent participation or
      without parent participation. METHODS: Null hypothesis and alternative hypothesis
      were established for discriminating full sibling from half sibling in two
      circumstances: two children with single-parent and without parent participation.
      Conditional probabilities of the genetic evidentiary under null and alternative
      hypotheses were calculated according to the Bayesian theory. The likelihood
      ratios were established with the conditional probability under alternative
      hypothesis division that under null hypothesis, followed with simplification. All
      the formulae were validated in a real case. RESULTS: While mother or fathers'
      genetic information available in differentiating full sibling from half sibling,
      14 different genotype combinations could be shared by the two detected children
      at a given locus and the likelihood ratio could be calculated with 5 different
      formulae respectively. While both parents' genetic information unavailable, 11
      different genotype combinations could be shared and the likelihood ratio could be
      calculated with 7 different formulae respectively. It was validated in a real
      case that the power of the likelihood ratio method developed for discriminating
      full sibling from half sibling with single-parent participation was higher than
      that of the ratio of full sibling index over half sibling index. CONCLUSION: The
      formulae of likelihood ratio developed are useful for discriminating full sibling
      from half sibling with single-parent participation or without parent
      participation.

PMID- 22619805
TI  - [Detection of matrix metalloproteinase-11 in menstrual blood by enhanced
      chemiluminescence method].
AB  - OBJECTIVE: To explore the forensic application value of detection of matrix
      metalloproteinase-11 (MMP-11) in menstrual blood by enhanced chemiluminescence
      method. METHODS: Menstrual blood, vaginal swab, peripheral blood, saliva stain,
      urine stain and semen stain were collected to detect whether or not there were
      MMP-11 using enhanced chemiluminescence method. The specificity and reliability
      of the MMP-11 assay along with its sensitivity were evaluated. RESULTS: The
      positive detection rate of MMP-11 in menstrual blood was 89.47%, whereas no MMP
      11 was found in vaginal swab, peripheral blood, saliva stain, urine stain and
      semen stain. When 25 microL sample was added, the mass concentration of protein
      was 1.329 microg/microL, then MMP-11 could be detected. A positive detection rate
      of 89.58% was observed in MMP-11 positive menstrual blood samples after stored at
      4 degrees C for 20 months. CONCLUSION: Enhanced chemiluminescence method is
      sensitive and specific for detecting MMP-11, and can be applied to distinguish
      menstrual blood from common stain such as peripheral blood, vaginal fluid.

PMID- 22619806
TI  - [Distribution specificity of human fucosyltransferase 5 and its expression and
      localization in spermatids].
AB  - OBJECTIVE: To investigate distribution specificity of human fucosyltransferase 5
      (FUT5) as well as its expression and localization in spermatids. METHODS: Human
      semen, vaginal swab, saliva and venous blood from healthy individuals were
      collected. The spermatids were isolated and the spermatid membrane protein was
      then extracted. Expression levels of FUT5 from human spermatid membrane, seminal
      plasma, vaginal fluid, saliva and serum were detected by immunoblotting
      technique. The expression and localization of FUT5 in spermatids were analyzed by
      immunofluorescent method. RESULTS: Immunoblotting technique showed that FUT5 was
      expressed on spermatid membranes and in serum, but not in seminal plasma, vaginal
      fluid and saliva. The expressed FUT5 on spermatids was mostly localized on head
      of spermatids by fluorescent microscopy, suggesting that there was certain amount
      of FUT5 on human spermatid membrane, and the spermatids might be isolated from
      mixed stains with vaginal fluid by antigen-antibody reaction. CONCLUSION: Human
      FUT5 shows a characteristic distribution specificity, and this feature may be
      used for identification of mixed stain involved in criminal sexual offence in
      future forensic practice.

PMID- 22619807
TI  - [Effects of ketamine and alcohol on learning and memory impairment in mice].
AB  - OBJECTIVE: To study the effects of ketamine and alcohol on learning and memory in
      mice and its possible mechanism. METHODS: Forty mice were divided into 4 groups:
      normal control group, ketamine group, alcohol group, and alcohol plus ketamine
      group. Ketamine and alcohol were given by intraperitoneal injection and
      intragastric administration, respectively, 1 time per day, for 14 days. The
      ability of learning and memory in mice was tested by the method of step-down and
      Morris water maze. Acetylcholine (ACh) and 5-hydroxy tryptamine(5-HT) in mice
      brain tissue were analyzed for the possible mechanism. RESULTS: (1) Step-down:
      The treatment groups lessened the latency and added wrong times (P < 0.05). The
      number of errors in the combined treatment group significantly increased
      comparing with the single drug treatment group (P < 0.05). (2) Morris water-maze:
      The treatment groups prolonged the latency (P < 0.05), reduced the target
      quadrant activity time significantly (P < 0.05), and decreased the numbers of
      crossing the former platform significantly (P < 0.05). (3) Biochemical index
      determination: The concentrations of ACh and 5-HT in treatment groups decreased
      significantly (P < 0.05), showed a more decreasement comparing with the single
      drug treatment group. CONCLUSION: Ketamine has a synergistic effect with alcohol
      on learning and memory impairment in mice, which may be related to the common
      inhibitive effect on the ACh and 5-HT.

PMID- 22619808
TI  - [Forensic investigation of 127 unidentified corpses in Shaoxing City].
AB  - OBJECTIVE: To explore the unidentified corpses in Shaoxing city in recent years
      to provide the experience for these types of corpse examination and forensic
      identification. METHODS: One hundred and twenty-seven unidentified corpses were
      collected and analyzed in the period from January 2009 to June 2011. The scene
      investigation, clothing examination and information of forensic investigation
      were collected and analyzed. RESULTS: Most of the unidentified corpses are the
      young male. Of them, there are 3 homicide cases. There are 92 cases (72.44%) of
      the corpses was found with all clothes and 72 cases (56.69%) with the belongings.
      There are 63 cases (49.61%) of the cases was died from downing and 15 cases
      (11.81%) was died from hypothermia and starvation. Cause of death in 25 cases
      (19.69%) was undetermined. CONCLUSION: The most of unidentified corpses in
      Shaoxing are found in water and died from accidents. The degree of corpse
      putrefaction is the principal factor to analyze the cause of death.

PMID- 22619809
TI  - [Low volume amplification in single cell separation and inspection].
AB  - OBJECTIVE: To establish optimal amplification conditions with the application of
      0.2 mL test tube in single cell separation and inspection. METHODS: Oral
      epithelium cell suspension was prepared. Five or ten cells were collected with
      0.2 mL test tube. Then DNA were amplified with Identifiler Plus kit in three
      different conditions in which the proteinase K addition, gold enzyme
      concentration in PCR reaction, and PCR reaction cycles were adjusted separately.
      Finally the detection rate, allelic dropout rate and artificial alleles were
      compared among the groups. RESULTS: In these 3 different conditions: addition of
      proteinase K, addition of 0.4 microL gold enzyme in PCR reaction, and use of 32
      cycles, the detection rate was higher and allelic dropout rate was lower than the
      other conditions. CONCLUSION: In single cell separation and inspection, the usage
      of 0.2 mL test tube could be an effective supplement to chip-low volume
      amplification.

PMID- 22619810
TI  - [Mechanism of methamphetamine intoxication and its medical identification].
AB  - Methamphetamine (MA) is a representative drug of amphetamine-type stimulants for
      central nervous system and has become one of the most dangerous drugs in the
      world recently. The present article reviews the pharmacological effects,
      distribution, metabolism, intoxication mechanism, the effects of MA on
      cardiovascular and central nervous systems of MA, and the current situation of
      forensic investigation on MA.

PMID- 22619811
TI  - Financial, operational assessment key to improving RCM: By establishing a
      committed partnership of third-party resources and internal staff, provider
      organizations can be proactive rather than reactionary.

PMID- 22619812
TI  - Keep RCM in check: Practices that are successful technology adopters consistently
      outperform their peers.

PMID- 22619813
TI  - Next-gen provider payment-processing solutions lower cost: those paper-based
      lockbox solutions are a thing of the past.

PMID- 22619814
TI  - More functions, better healthcare: Tablet PCs help increase efficiency, accuracy
      and reduce the risk of healthcare-associated infections (HAIs).

PMID- 22619815
TI  - Getting the lead out.

PMID- 22619816
TI  - Overcoming today's PACS/RIS challenges.

PMID- 22619817
TI  - Conquering the complexity of storage: Converged medical infrastructure can
      increase storage capacity by improving the IT environment as whole.

PMID- 22619818
TI  - Is cloud storage right for your organization? Many healthcare organizations are
      looking to third-party vendors for help.

PMID- 22619819
TI  - Best practices in healthcare disaster recovery planning: The push to adopt EHRs
      is creating new data management challenges for healthcare IT executives.

PMID- 22619820
TI  - Goodbye paper, hello results: Kronos scheduling solution balances employee and
      business needs for WellStar.

PMID- 22619821
TI  - Network upgrade saves thousands: Navos, a non-profit mental health organization
      based in Seattle, went from T1 to Ethernet and reduced back-up time by 80
      percent.

PMID- 22619822
TI  - How to choose the right tablet: Save time, reduce errors and ensure that the most
      up-to-date information stays at the clinician's fingertips throughout all stages
      of the care-delivery process.

PMID- 22619823
TI  - [Former brewery worker with liver cirrhosis: beer was not the cause!].

PMID- 22619824
TI  - [Addicted to alcohol and drugs. "Addiction in the elderly is not a side issue"
      (interview by Dr. Robert Bublak)].

PMID- 22619825
TI  - [Rip-offs by by unscrupulous providers of medical directories. Only one thing
      helps: do not pay!].

PMID- 22619826
TI  - [Physician networks: additional fees with collective contracts].

PMID- 22619827
TI  - [Distribution of fees back to national health service level: a new tool for
      managing fee deficits?].

PMID- 22619829
TI  - [Good preparation is necessary: travel with rheumatoid arthritis].

PMID- 22619828
TI  - [Targeted therapy makes it possible: pain free despite rheumatoid arthritis].

PMID- 22619830
TI  - [Even patients with rheumatoid arthritis should be physically active: thanks to
      sports, fewer clinic visits].

PMID- 22619831
TI  - [Naturopathy consultation. Chronic inflammatory bowel diseases].

PMID- 22619832
TI  - [Antibiotics in otitis: a history of chorea minor entitles more generous
      treatment].

PMID- 22619833
TI  - [Magnesium is no longer effective: calf cramps are becoming more severe].

PMID- 22619834
TI  - [Pruritus, blisters, anhidrosis: how diabetes effects the skin].

PMID- 22619835
TI  - [Cardiology and heart surgery: no longer in competition but together: the future
      of cardiology lies with the cardiology team].

PMID- 22619836
TI  - [Pulmonary embolism after spinal operation: what lies in the pulmonary artery?].

PMID- 22619837
TI  - [Emergency treatment of children].

PMID- 22619838
TI  - [Acute abdominal pain in children].

PMID- 22619839
TI  - [Fever in infants: harmless or dangerous? How to find out].

PMID- 22619840
TI  - [First signs of a decubitus ulcer?].

PMID- 22619841
TI  - [Estrogen therapy prevents the aging of the skin].

PMID- 22619842
TI  - [Contra: opposing a simplistic hormone replacement therapy].

PMID- 22619843
TI  - [New antihypertensive drugs].

PMID- 22619844
TI  - [5 plant antibacterial combination: bioflavonoids in acute bacterial
      rhinosinusitis].

PMID- 22619845
TI  - Tar heel footprints in health care: Brenda K. McCall.

PMID- 22619846
TI  - Treating pediatric obesity in the primary care setting to prevent chronic
      disease: perceptions and knowledge of providers and staff.
AB  - BACKGROUND: The national and international epidemic of chronic disease, including
      among children, is largely fueled by increasing obesity. It is recommended that
      primary care play a key role in the treatment of pediatric obesity. METHODS: A
      written survey was administered to providers and staff at 13 primary care
      practices across North Carolina, assessing perceptions on multiple dimensions of
      pediatric obesity treatment and knowledge of dietitian services. RESULTS: The
      response rate for the survey was 66.9% (n = 273). Although providers reported
      feeling comfortable and confident in many areas of childhood obesity, perceived
      effectiveness was low. Moreover, comfort and confidence were lower for non
      primary care providers (PCPs) involved in obesity treatment than for PCPs, and
      PCP comfort and confidence levels were low for the ability to conduct
      motivational interviewing and for knowledge of billing for obesity as a
      diagnosis. Personnel perceived that there were benefits to having a registered
      dietitian (RD) in their practice and generally understood RD capacity. Survey
      results provided no evidence that integration of an RD into the practice changed
      perceptions or knowledge over the course of 1 year. LIMITATIONS: The present
      study included only 13 practices, mostly rural and all of at least moderate size.
      CONCLUSION: Significant change is required if primary care practices are to play
      the role envisioned for them in stemming childhood obesity and chronic disease.
      Change will require identifying and addressing specific knowledge and skill gaps,
      such as those identified in this study. Respondents' positive perceptions of the
      benefits of RD integration suggest the importance of exploring this clinical
      model.

PMID- 22619847
TI  - State Medicaid policies and the health care access of low-income children with
      special health care needs living in the American South.
AB  - BACKGROUND: The policy correlates that improve or impede the health care access
      of children with special health care needs (CSHCN), and particularly children
      living in the South, are not well understood. METHODS: We analyzed data from the
      2005-2006 National Survey of CSHCN (n = 4560 Southern children and 8788 non
      Southern children). State Medicaid policy predictors included the frequency of
      Medicaid eligibility renewals (6 or 12 months) and the level of reimbursement
      provided for high-complexity and moderate-complexity pediatric office visits.
      Hierarchical generalized linear modeling was used to examine the association
      between state Medicaid policy features and 5 indicators of health care access
      (delayed or foregone care, difficulty using services, difficulty getting
      referrals, unmet routine care needs, and unmet specialty care needs), after
      controlling for child, family, and state factors. RESULTS: Low-income Southern
      CSHCN who lived in states with less-frequent Medicaid eligibility renewal
      requirements and higher health care provider reimbursement rates had
      significantly better health care access than did their Southern counterparts in
      states with more-frequent Medicaid eligibility renewals and lower reimbursement
      rates. LIMITATIONS: These data are cross-sectional, and causality cannot be
      inferred. CONCLUSION: Policymakers interested in addressing state budget gaps
      should be concerned that doing so by increasing the frequency of Medicaid
      eligibility renewals or by cutting health care provider reimbursement rates may
      well result in adverse health care access for low-income Southern CSHCN.

PMID- 22619848
TI  - Physical therapy services utilization and length of stay for obese patients
      following traumatic leg fracture.
AB  - BACKGROUND: Obesity is an increasing epidemic that can complicate the treatment
      of simple injuries and can increase health care costs. The purpose of the present
      study was to determine whether obesity is a factor in the utilization of
      inpatient physical therapy services and length of stay following a traumatic
      lower leg fracture. METHODS: A retrospective study of patients admitted to the
      hospital in 2005 and 2006 with a primary discharge diagnosis of lower leg or
      ankle fracture was conducted. Inclusion criteria were age > or = 18 years, only 1
      involved lower extremity, and nonweight-bearing on the affected extremity per
      physician orders. Patients were excluded from the study if they had a fibular
      fracture only, pathological fractures, multiple trauma, severe cardiac or
      vascular comorbidities, or cognitive impairments. Data were compiled into 3
      categories on the basis of body mass index (BMI): < 30, 30-35, > 35. Physical
      therapy services were measured in 15-minute units of time. These data were
      analyzed by within-group and between-group comparisons and with regression
      analysis. RESULTS: A total of 181 patients with a primary discharge diagnosis of
      distal lower extremity or ankle fracture were included in the study. Patients
      with a BMI >35 used more physical therapy services (mean services, 9.8 units)
      than did patients with a BMI of 30-35 (mean services, 6.2 units) or a BMI <30
      (mean services, 5.6 units) (P = .001). Length of stay was also highest among
      patients with a BMI >35. LIMITATIONS: Factors other than BMI may be associated
      with length of stay and physical therapy use and may confound the association.
      CONCLUSION: Previous studies have shown that there is an increase in health care
      utilization among the bariatric population. The present study demonstrates
      similar findings for physical therapy services. Increased length of stay and
      physical therapy utilization among the bariatric population also result in
      increased staff utilization and equipment costs.

PMID- 22619849
TI  - Care transitions. Introduction.

PMID- 22619850
TI  - Improving care transitions means more than reducing hospital readmissions.
AB  - Hospital readmissions are not only expensive, avoidable, and dangerous, but are
      also indicative of the most dysfunctional elements of US health care. The Patient
      Protection and Affordable Care Act places great emphasis on reducing preventable
      readmissions by building care systems that are patient-centered and that remove
      arbitrary silos of care. Hospitals that perform poorly on this measure will
      experience significant financial penalties beginning this fiscal year. In the
      short term, decreasing readmission rates will eliminate waste and enhance patient
      recovery from major illness. However the real vision is to ensure that vulnerable
      patients, particularly the chronically ill, benefit from coordinated, patient
      centered systems that maintain functional independence, improve quality of life,
      and provide comfort without the trauma, expense, and displacement that
      unnecessary hospitalization often entails. The commentaries published in this
      issue of the NCMJ portray some of the most significant barriers to smooth
      transitions and reducing readmission rates and describe some of the nascent North
      Carolina and national solutions that demonstrate promise in real world
      situations.

PMID- 22619851
TI  - Collaborative accountability for care transitions: the community care of North
      Carolina transitions program.
AB  - Community Care of North Carolina initiated efforts to improve care transitions
      for North Carolina Medicaid recipients in 2008. The transitions program is now
      statewide, serving more than 4,000 patients every month, virtually every North
      Carolina hospital, and more than 1,400 primary care practices. This commentary
      describes program components, early outcomes, and future challenges.

PMID- 22619852
TI  - A series of well-coordinated dismounts.

PMID- 22619853
TI  - Organizing communities around care transitions: the community connections
      experience.
AB  - The Community Connections initiative provides an example of building
      collaboration and partnerships across traditional boundaries--public-private,
      medical home, and community-based services--to improve care transitions and
      support for older adults and adults with disabilities. This approach was inspired
      by the self-governance and community engagement model, with the knowledge,
      experience, and participation of community stakeholders.

PMID- 22619854
TI  - Practices to improve transitions of care: a national perspective.
AB  - Improving transitions of care has significant importance to our health care
      system. While care transitions has been studied and researched by many
      individuals over the past 20 years, more work is needed to further improve the
      process. Those beginning to focus on transitions need not begin from scratch, but
      can use information and research from national and regional collaborative models,
      as well as other tools and resources to enhance the quality of transitions
      programs.

PMID- 22619855
TI  - An evidence-based strategy for transitioning patients from the hospital to the
      community.
AB  - Improving transitional care from hospital to home requires comprehensive and
      highly coordinated intervention during the immediate days following discharge.
      The Hospital to Home Program addresses both medical and social needs, prevents
      unnecessary readmissions, promotes improvements in patient perceptions of
      physical and mental health, and results in excellent patient satisfaction.

PMID- 22619856
TI  - Transitions to and from nursing facilities.
AB  - Many nursing home transition barriers are manmade and avoidable. PPACA is
      encouraging improvement and reduced unnecessary hospitalizations through
      incentives and penalties. Providers are responding through a variety of internal
      and collaborative models. The resulting communication, technology, education, and
      emphasis can improve the quality of life for the people served.

PMID- 22619857
TI  - Intentional collaboration: addressing transitions in care for people with severe
      and persistent mental illnesses.
AB  - This commentary explores transitions in care for people who have severe and
      persistent mental illnesses and reside in long-term care communities. Challenges
      and historical approaches as well as barriers to successful transitions are
      examined. Recent policy changes in North Carolina are discussed and
      contextualized in emerging evidence-based practices that emphasize intentional
      collaborative efforts.

PMID- 22619858
TI  - Now where was I going? The challenge of care transitions for the cognitively
      impaired.
AB  - Transitions in care settings can be disconcerting to anyone, but they can be
      particularly difficult for people with cognitive impairment. MemoryCare's design
      of integrated clinical and care management services is well suited to minimizing
      the preventable morbidity that can accompany transitions in health care for
      cognitively impaired older adults at high risk for poor outcomes.

PMID- 22619859
TI  - Improving care coordination in the specialty referral process between primary and
      specialty care.
AB  - There is growing evidence of sub-optimal care coordination in the US. Care
      coordination includes the specialty referral process, which involves referral
      decision-making and information transfer between primary and specialty care. This
      article summarizes the evidence of sub-optimal care coordination in this process,
      as well as potential strategies to improve it.

PMID- 22619860
TI  - Care transitions: an essential part of the delivery of health care.

PMID- 22619861
TI  - Transitions of care: Blue Ridge Community Health Services.

PMID- 22619862
TI  - North Carolina Alliance for Effective Care Transitions.

PMID- 22619864
TI  - The future is always full of opportunities.

PMID- 22619863
TI  - 2011 North Carolina Child Health Report Card.

PMID- 22619865
TI  - The evolution of the hospital system in China.
AB  - The Chinese health care system has improved rapidly, especially in the areas of
      health insurance and the movement toward universal coverage. Public hospital
      reforms have been much slower, however, and have encountered significant
      challenges. The objective of this article is to describe the current challenges
      in public hospital reform in China through the lens of the evolution of the
      hospital system. The authors also draw general lessons that could be applied to
      other countries.

PMID- 22619866
TI  - What have we learned from Japan's major earthquake, tsunami and nuclear incident?
AB  - Ten months have passed since the Great East Japan Earthquake on March 11, 2011.
      Although we have tried our best to support the affected areas for te last ten
      months, people and hospitals in these areas are still suffering from various
      calamities and these include damage from the earthquake, tsunami, nuclear
      incident, harmful rumors, and manmade disaster. In this articles, various
      supportive efforts of the Japan Hospital Association (JHA) in the acute, mid
      term, and long-term stages are described. Based on our experience, we propose to
      establish a new medical support system and reconstruction scheme for the health
      care delivery system in the affected areas.

PMID- 22619867
TI  - Public policy and medical tourism: ethical implications for the Egyptian health
      care system.
AB  - Egypt's medical tourism industry has been experiencing tremendous growth.
      However, Egypt continues to lack the necessary investment in its public health
      system to effectively care for its population. Current policy and the emergence
      of medical tourism have led to unequal health care access, resulting in high a
      prevalence of infectious diseases and lack of resources for its most vulnerable
      populations. As a new Egyptian government emerges, it is important for
      policymakers to understand the critical issues and ethical concerns of existing
      health policy. This understanding may be used to propose new policy that more
      effectively allocates to care for Egypt's population.

PMID- 22619868
TI  - Creators of private health care businesses in the Democratic Republic of the
      Congo: profile and sources of start-up funds.
AB  - A survey was conducted in Jury 2010 to explore the creation of private health
      care businesses in Mbuji Mayi, the capital city of the Eastern Kasai Province
      (EKP), Democratic Republic of the Congo (DRC). The survey yielded 68 responses.
      The results indicated that the entrepreneurs were predominantly Congolese men
      with backgrounds in the health services field who had raised their start-up
      capital mostly from personal savings or from friends and family. Their
      businesses, which were mostly in the form of sole proprietorships, were likely to
      be located in areas underserved by government-owned medical facilities.

PMID- 22619869
TI  - The proposed Nelson Mandela Children's Hospital, Johannesburg: providing the best
      care for children in the developing world.
AB  - Construction will soon commence on the Nelson Mandela Children's Hospital (NMCH)
      in Johannesburg, South Africa. The Hospital will have 250-300 beds and will
      provide tertiary and quaternary care to children in specific Centers of
      Excellence. Admission to this referral facility will be based entirely on medical
      needs. The disciplines that are catered for include Paediatric surgery, oncology,
      nephrology, cardiology, intensive care and imaging. The NMCH will be South
      Africa's first "Private Hospital - Not for Gain". Funding for capital expenditure
      is currently being raised by the Trust. Operational expenditure will come from
      the Department of Health, private insurers and neighbouring governments.

PMID- 22619870
TI  - Assessment of organizational management in the district health centers of
      Ulaanbaatar.
AB  - This cross sectional study assessed organizational management of district
      hospitals in terms of operational planning and follow-up, program and guidelines,
      organizational and work routines, personnel, facilities and medical equipment,
      process orientation and control. Four district health centers employees (n=208)
      were involved. We assessed using Likert-type scale ranging from 1 (very poor) to
      5 (excellent). The overall mean score given to organizational management was 3.09
      +/- 0.91. There was statistically significant difference in assessing operational
      planning and follow-up (p<0.044) and control (p<0.014) by different occupations.
      In conclusion, the findings confirm our hypothesis that there is a lack of
      management capacity within the public sector in Ulaanbaatar.

PMID- 22619871
TI  - Improvement of efficiency and safety in hospitals starts in the beginning of the
      planning phase and influences patient safety, staff, hygiene as well as
      logistics, and efficiency within the entire hospital.
AB  - To increase patient safety and hospital efficiency a new stepwise planning
      methodology including an early peer review of the future design is shown in the
      article as well as innovative training concepts for hospital staff.

PMID- 22619872
TI  - Care for noncommunicable diseases (NCDs): time for a paradigm-shift.
AB  - Noncommunicable diseases (NCDs) are on the rise and multi-morbidity becomes more
      and more the rule, no longer the exception. For these patients, disease
      management programs are having difficulty in realizing comprehensive care.
      Therefore, a paradigm-shift from "problem-oriented" toward "goal-oriented" care
      is needed, reorienting the care toward the goals formulated by the patient. By
      doing so, we will avoid care that may lead to "inequity by disease".

PMID- 22619873
TI  - What are you prepared to see?
AB  - A hospital system is made up of interconnecting circles of complex activity;
      however, we are conditioned to see and think in straight lines. What we see
      depends on what we are prepared to see. This article asks the question: What do
      you see in terms of patient safety and quality of care?

PMID- 22619874
TI  - Enhanced activation and restorative care.
AB  - As the Canadian population ages, it becomes increasingly important for hospitals
      to address and implement programs and policies that ensure elderly patients are
      receiving the right care in the right place at the right time. Despite the vast
      majority of elderly patients being healthier than ever, it is important to
      recognize the rapid deconditioning that occurs when they are admitted to an acute
      care hospital. Although it is recognized that children need to be treated
      differently, we fail to recognize the same is true for older adults. The Enhanced
      Activation Program was conceptualized during consultation with community partners
      while discussing the aging at home strategy. It was during these consultations
      that gaps in service for the frail elderly were identified and the Enhanced
      Activation Program was developed.

PMID- 22619875
TI  - Redesigning care delivery in British Columbia.
AB  - Phase 1 of this initiative was designed to examine the current state of practice
      in acute care and to provide administrators with research evidence for
      identifying areas for improvement. Data were collected through observational
      research using function analysis augmented by a staff survey and interviews. Data
      were collected from 17 acute care sites across Vancouver Island and the Mainland
      of British Columbia involving four health authorities.

PMID- 22619876
TI  - Creating and sustaining a collaborative model of care.
AB  - For the past 3 years, Toronto East General Hospital staff and leadership have
      been involved in the design, implementation, and evaluation of a transformational
      change to the model of patient care. The purpose of the new model is to enhance
      quality, safety, and patient satisfaction through a redefinition of our approach
      to the patient experience. The evaluation framework for the coordinated care team
      (CCT) model of care addressed safety and quality outcomes, patient satisfaction,
      staff and physician satisfaction, and resource impact. Results of the evaluation
      suggest that the introduction of the CCT model using the patient care bundle can
      have a significant impact on the patient experience through enhanced access to
      bedside care as well as improved quality and safety outcomes. This article is a
      follow-up to the article on the development of the model published in Forum (Fall
      2009). It extends upon the previous article through an overview of the model as
      it evolved, a discussion of the first-year evaluation for three pilot units, and
      lessons learned regarding the change process.

PMID- 22619877
TI  - Patient management in the emergency department by advanced care paramedics.
AB  - We describe an emergency department process using Advanced Care Paramedics in the
      management of patients identified as ambulatory and low acuity, or those able to
      be managed without an emergency nurse. Patients streamed in this way had shorter
      stays than other emergency patients, without affecting the care of the latter.
      The process was associated with improved patient flow indicators in spite of an
      increased patient burden.

PMID- 22619878
TI  - Building an international public health academic partnership: the Alberta
      Lithuania experience.
AB  - The schools of public health at the University of Alberta and the Lithuanian
      University of Health Sciences have developed a partnership committed to a variety
      of collaborations (e.g., faculty/student exchanges and joint projects). Our
      initial efforts have resulted in the initiation of joint projects, important
      connections between numerous institutions/academics, and planning for future
      efforts within and beyond the partnership. The positive potential for such
      partnerships is significant, and a number of strategies for successful
      implementation are suggested.

PMID- 22619879
TI  - Organizational ethics: no longer the elephant in the room.

PMID- 22619880
TI  - Prevalence of infectious diseases of immigrant workers receiving health
      examinations at Rajavithi Hospital.
AB  - BACKGROUND: There are rapidly increasing numbers of immigrant workers coming for
      jobs in Thailand. These immigrant workers often harbor some serious communicable
      diseases. OBJECTIVE: To describe the prevalence of infectious diseases in these
      immigrant workers. MATERIAL AND METHOD: This is a retrospective study of
      immigrant workers who presented for check-ups needed for work permits at
      Rajavithi Hospital during 1 January 2008 to 31 December 2010. They were examined
      for serious infectious disease including pulmonary TB, elephantiasis, leprosy,
      syphilis and malaria. Their health status was analyzed. RESULTS: A total of
      102,090 immigrant workers were examined. The majority of cases were female
      (58.4%) and 94.3% of the population was under the age of 40. Workers from Burma
      constituted the most cases, (78.9%), followed by workers from Laos (14.0%) and
      Cambodia (7.0%). The prevalence of infectious diseases in all workers was 1,612.3
      cases per 100,000 population. Patients with pulmonary TB, elephantiasis, leprosy,
      syphilis and malaria were 1,112.7, 7.8, 4.9, 465.3 and 21.5 cases per 100,000
      population respectively. The prevalence of TB in Burmese, Lao and Cambodian
      workers was 1,119.3, 885.9 and 1,493.2 cases per 100,000 population respectively.
      The prevalence of syphilis in Burmese, Lao and Cambodian workers was 467.8, 258.1
      and 851.2 cases per 100,000 population respectively. CONCLUSION: Immigrant
      workers with infectious diseases were 1,612.3 cases per 100,000 population. Those
      harboring these serious transmitted diseases may be an important factor in these
      diseases becoming widespread in Thailand.

PMID- 22619881
TI  - Vancomycin-resistant enterococci (VRE) isolates isolated in Rajavithi Hospital
      between 1999 and 2009.
AB  - From 1999 to 2009, a total of 10,470 clinical enterococcal strains from patients
      in Rajavithi Hospital were isolated. Of these, 201 (1.9%) vancomycin-resistant
      enterococci (VRE) including 199 (99.0%) Enterococcus faecium and 2 (1.00%)
      Enterococcus faecalis were found. The incidence of VRE was 1.8% in 1999, 3.3% in
      2000, 5.1% in 2001, 1.0% in 2002, 0.0% in 2003 and 2004, 1.1% in 2005, 4.7% in
      2006, 1.9% in 2007, 2.2% in 2008 and 0.9% in 2009. Seventy-one VRE isolates were
      classified to VanA phenotype (69 VanA E. faecium and 2 VanA E. faecalis) and 130
      were classified to VanB phenotype (VanB E. faecium). The rate of inpatient
      departments (IPD)-associated VRE (199 (99.0%) VRE isolates) was significantly
      greater than the incidence of outpatient departments (OPD)-VRE (2 (1.0%) VRE
      isolates). VRE were found in medical (33.7%), ICUs (15.6%) and surgical (15.1%)
      wards. VRE were mostly found in urine, 64.2%, following in pus, blood, genital
      and sputum specimens, 21.9%, 9.0%, 3.5% and 1.4%, respectively. VRE, especially
      vancomycin resistant E. faecium, were multidrug-resistant (resistance to
      ampicillin, tetracycline, norfloxacin, ciprofloxacin, erythromycin and
      gentamicin). All strains of VRE were fully susceptible to linezolid.

PMID- 22619882
TI  - Associated factors for diagnosis of influenza A (H1N1) 2009 in patients
      presenting to Rajavithi Hospital.
AB  - BACKGROUND: The pandemic influenza A (H1N1) 2009 was a global outbreak of a new
      strain of influenza A virus. The associated factors of influenza A (H1N1) 2009
      infection in Thailand have not been well studied. OBJECTIVE: To determine the
      associated factors for diagnosis of influenza A (H1N1) 2009. STUDY DESIGN:
      Retrospective analytical study MATERIAL AND METHOD: A total 430 patients who had
      influenza-like symptoms from the out-patient department of Rajavithi Hospital in
      Thailand were analyzed by collecting the hospital charts of the patients between
      1 June 2009 and 31 August 2009, total 3 months. The patients' personal
      information, signs and symptoms, laboratory data and throat swab for influenza A
      (H1N1) 2009 virus confirmed by real time reverse transcription polymerase chain
      reaction were analyzed. RESULTS: There were 152 (35.3%) influenza A (H1N1) 2009
      confirmed-case patients, 100 (65.80%) were female and 52 (34.2%) were male. The
      average age was 28.2 +/- 15.6 years and the most occupation were housewives
      (56.6%) and students (36.8%). The patients presented with acute fever (100.00%),
      cough (95.4%), rhinorrhea (66.4%), dyspnea (27.0%) and the mean duration of fever
      was 4.3 +/- 2.9 days at the time of sample collection. Laboratory finding such as
      leukocytes count, platelets count, lactate dehydrogenase and chest x-ray were
      normal in most cases. The associated factors of influenza A (H1N1) 2009 infection
      were age < 35, pregnancy, rhinorrhea and white blood count < 10,000 cells/ml3.
      CONCLUSION: The associated factors of influenza A (H1N1) 2009 were age < 35
      years, pregnancy rhinorrhea and white blood count < 10,000 cells/ml3.

PMID- 22619883
TI  - Prevalence of Helicobacter pylori infection in patients with peptic disease.
AB  - BACKGROUND: Helicobacter pylori is one of the most common human infections
      worldwide. It has been established as etiology of chronic gastritis and peptic
      ulcer disease, gastric adenocarcinoma and mucosal associated lymphoid tissue
      lymphoma (MALT). During this decade, there have been some reports showing a
      decline in global prevalence of H. pylori infection and peptic diseases including
      in many Asian countries. OBJECTIVE: To study the H. pylori infection in patients
      with peptic diseases, association with other factors and comparison to previous
      data. MATERIAL AND METHOD: Retrospective observational study of endoscopic
      reports for upper gastrointestinal tract diseases in patients with peptic
      diseases from October 2009 to September 2010 at the Endoscopic Unit, Department
      of Medicine, Rajavithi Hospital. Patients were examined for the presence of H.
      pylori infection by rapid urease test (RUT) or histology staining. RESULTS: Five
      hundred and seventy patients with a mean age of 55.0 +/- 16.02 years with peptic
      diseases were studies. Endoscopic findings showed 106 GU patients (18.6%), 29 DU
      patients (5.1%), 3 combined GU and DU patients (0.5%) and 432 NUD patients
      (75.8%). The prevalence of H. pylori infection were 64% (365 of 570 patients).
      Prevalence of H. pylori infection were 61.3% of NUD cases, 68.9% of GU cases,
      82.8% in DU cases and 100% in combined GU and DU cases. Comparison with previous
      data (Anantapunpong S. Rajavithi Med J 1999; 10: 17-26), the prevalence of H.
      pylori infection overall and in DU are not changed but in NUD and GU are
      increased. CONCLUSION: The prevalence of H. pylori infection is still high in
      peptic diseases. The patients with age more than 50 years have more GU, less NUD
      than the younger groups. In comparison with a previous study, the prevalence of
      H. pylori infection in overall and in DU are not changed but in NUD and GU are
      increased.

PMID- 22619884
TI  - Prevalence of single nucleotide mutation in clarithromycin resistant gene of
      Helicobacter pylori: a 32-months prospective study by using hybridization real
      time polymerase chain reaction.
AB  - Polymerase chain reaction (PCR) for detection of single nucleotide mutations in
      23S rRNA gene of clarithromycin resistance Helicobacter pylori were investigated
      worldwide. In Thailand, the prevalence of these mutations had not been
      extensively investigated. The authors conducted a 32-months prospective study to
      estimate the prevalence of clarithromycin resistant Helicobacter pylori and to
      compare the sensitivity and specificity of hybridization real time PCR for 23S
      rRNA gene of Helicobacter pylori detection with the combination of rapid urease
      test, immunohistochemistry straining and Helicobacter pylori culture. A total of
      200 patients with endoscopic examination with gastric biopsy were enrolled from
      January 2006 to September 2008. Eight gastric specimens were biopsied and
      performed rapid urease test, immunohistochemistry straining for Helicobacter
      pylori, Helicobacter pylori culture and hybridization real time PCR for 23S rRNA
      dectection, as well as single nucleotide mutation detection, such as G2111A,
      A2115G A2142G, A2143G andA2144G. The clarithromycin susceptibility of
      Helicobacter pylori isolated was determined by E-test. The prevalences of
      clarithromycin, amoxicillin, metronidazole and tetracycline resistance were
      13.8%, 21.3%, 55.0% and 8.8%, respectively. Most of clarithromycin resistant
      Helicobacter pylori (81.80%) had very high minimal inhibition concentration (MIC)
      more than 256 microg/ml. The resistance to mutation gene at A2142G was found in 4
      patients (36.40%). Two patients were found to have multiple mutations at G2111A,
      A2115G and A2144G (18.20%). The sensitivity, specificity, positive predictive
      value, negative predictive value, likelihood ratio to test positive and
      likelihood ratio to test negative of hybridization RT-PCR in detecting 23S rRNA
      gene of Helicobacter pylori was 95.6%, 94.4%, 93.2%, 96.7%, 17.2 and 4.6,
      respectively. In conclusion A2142G mutation was most common and associated with
      high MIC. Hybridization RT-PCR had good sensitivity and specificity to detect 23S
      rRNA gene, as well as clarithromycin resistance gene mutation of Helicobacter
      pylori.

PMID- 22619885
TI  - Validation of appropriate reference genes for gene expression studies in human
      thyroid gland using real-time RT-PCR.
AB  - BACKGROUND: Gene-expression analysis is increasingly important in biological
      research, with real-time reverse transcription PCR (qRT-PCR) becoming the method
      of choice. The selection of reference genes is critical for gene expression
      studies because the expression of these genes may vary among tissues or cells and
      may change under certain circumstances. However there has not been any study that
      compares the stability of these reference genes in human thyroid specimens.
      Therefore, the authors studied the stability values and the appropriate reference
      genes expressed in thyroid specimens. MATERIAL AND METHOD: 25 human thyroid
      specimens were prospectively collected and extracted for their RNA. The candidate
      reference genes (hypoxanthine phosphoribosyl-transferase1 (HPRT1), ribosomal
      protein LI3a (RPLIA), beta-2-micro-globulin (B2M), beta-actin (ACTB) and
      glyceraldehyde-3-phosphate dehydrogenase (GAPD)) were amplified from these
      thyroid specimens using real-time RT-PCR. The stabilities of these candidate
      reference genes were analyzed using Normfinder software. RESULTS: The authors
      found that HPRT1 has the highest stability value (40.38 x 10(9)) while GAPD has
      the lowest stability value (85.46 x 10(7)). Therefore GAPD is the most stably
      expressed gene in thyroid specimens. CONCLUSION: Of the 5 genes studied, GAPD was
      found to be the best reference gene for gene expression studies in the thyroid
      gland. The present results may facilitate the choice of reference genes for
      expression studies in thyroid diseases.

PMID- 22619886
TI  - An open label, randomized controlled study of oral calcitriol for the treatment
      of proteinuria in patients with diabetic kidney disease.
AB  - BACKGROUND: The progression of diabetic kidney disease (DKD) is highly correlated
      with proteinuria. Previous studies have suggested that vitamin D treatment may
      reduce proteinuria and has the potential to delay the progression of renal
      disease. OBJECTIVE: To evaluate efficacy of oral calcitriol to decrease
      proteinuria in type 2 diabetic mellitus (T2DM) patients with DKD. MATERIAL AND
      METHOD: In this 16-week, open label, prospective, randomized controlled study, 91
      patients with T2DM with estimated glomerular filtration rate (eGFR) greater than
      15 ml/min/1.73 m2 and urine protein to creatinine ratio (UPCR) greater than 1 g/g
      were enrolled. They were randomly assigned to receive either oral calcitriol 0.5
      mcg twice weekly (n = 46) or without oral calcitriol (n = 45). The primary
      outcome was determined by the change of UPCR from baseline after 16 weeks of
      treatment of both groups. RESULTS: At randomization, the mean UPCR was 3.7 + 2.2
      g/g in the calcitriol group and 3.4 +/- 2.1 g/g in the control group. The mean
      UPCR at 16-week follow-up was 2.9 +/- 1.7 g/g in the calcitriol group and 3.5 +/-
      2.3 g/g in the control group. Percent changes in UPCR from baseline to the last
      evaluation in the calcitriol and control groups were -18.7% and +9.9% (p < 0.01)
      respectively. Patients with 30% or more decrement in proteinuria occurred 43.5%
      of the time in the calcitriol group and 11.1% in the control group (p < 0.01).
      The eGFR and blood pressure did not differ significantly between the two groups.
      No serious adverse side effects were noted in either group. CONCLUSION:
      Calcitriol treatment can reduce proteinuria in patients with DKD without serious
      adverse events.

PMID- 22619887
TI  - Quality of life in hemifacial spasm patient after treatment with botulinum toxin
      A; a 24-week, double-blind, randomized, cross-over comparison of Dysport and
      Neuronox study.
AB  - BACKGROUND: Hemifacial spasm (HFS) is a common movement disorder presented with
      unilateral, intermittent, irregular tonic or clonic contraction of facial
      expression muscles without any identifiable etiology. Comparison of quality of
      life (QoL) between Dysport and Neuronox has not been studied in HFS patients.
      OBJECTIVE: To evaluate the QoL after treatment with botulinum toxin A (Dysport
      and Neuronox) injection in HFS patient. MATERIAL AND METHOD: A 24-week, double
      blind, randomized, cross-over comparison of QoL in HFS patients after being
      treated with botulinum toxin A (Dysport) and botulinum toxin A (Neuronox) was
      performed. Assessment of QoL composed of hemifacial spasm-30 (HFS-30), medical
      outcome study short form 36 items (SF-36), abnormal involuntary movement scale
      (AIMS) and center for epidemiologic studies-depression (CES-D) questionnaire,
      were performed at week 0, week 12, and week 24. The 24-hour HFS diary, recorded
      for 4 weeks after treatment was also evaluated. RESULTS: Total of 26 HFS patients
      were enrolled between May 2010 and January 2011. The mean HFS-30, AIMS and CES-D
      were reduced after treatment without any difference between the two groups. The
      mean SF-36 was not changed in both groups. However mean HFS-30 (p = 0.09), AIMS
      (p = 0.02) and CES-D (p < 0.001) of all treated patients were reduced across the
      treatment period. Total intensity score of HFS, duration of facial muscles spasm
      per day and duration of functional impairment per day in Dysport group were
      significantly lower than the Neuronox group (p < 0.001). CONCLUSION: There was no
      difference between Dysport and Neuronox in the aspect of QoL in HFS patients.
      However, there was improvement of QoL after multiple botulinum toxin A injection.

PMID- 22619888
TI  - The efficacy of neoadjuvant paclitaxel-carboplatin chemotherapy followed by
      radical hysterectomy compared to radical hysterectomy alone in bulky stage IB2
      IIA cervical cancer.
AB  - OBJECTIVE: To compare the efficacy of neoadjuvant paclitaxel-carboplatin
      chemotherapy followed by radical hysterectomy with radical hysterectomy alone in
      patients with bulky cervical cancer stage IB2-IIA. MATERIAL AND METHOD: From
      January 2000 through December 2009, 80 patients with bulky cervical cancer stage
      IB2-IIA that received neoadjuvant paclitaxel-carboplatin chemotherapy (n = 40) or
      immediate primary surgery (n = 40) were reviewed. The efficacy of neoadjuvant
      chemotherapy on the basis of feasibility in operation and pathological prognostic
      factors and the percentage of patients who needed postoperative adjuvant
      concurrent chemoradiation therapy were compared. RESULTS: There were no
      significant differences between group in age, tumor size, FIGO staging,
      histologic type and grading at the time of diagnosis. All patients in neoadjuvant
      chemotherapy group successfully underwent radical hysterectomy. The pathological
      findings included tumor size, deep cervical invasion, parametrial involvement,
      positive surgical margin and lymphovascular space invasion were statistically
      significant decrease in neoadjuvant chemotherapy group. Nevertheless, the pelvic
      nodal metastasis was not different between both groups. Adjuvant concurrent
      chemoradiation therapy had a statistically significant decrease in the
      neoadjuvant chemotherapy group. CONCLUSION: Neoadjuvant chemotherapy significant
      by improves the feasibility in operation and the pathological prognostic factors,
      and decreases the percentage of patients who needed postoperative adjuvant
      concurrent chemoradiation therapy.

PMID- 22619889
TI  - Assessment of blood flow in hemodialysis patients using buttonhole technique for
      arteriovenous fistula by ultrasound dilution.
AB  - BACKGROUND: The rope-ladder technique is the traditional AVF cannulation
      technique for HD. The buttonhole technique with repeated puncture with a blunt AV
      needle into a single selected site of AVF is a reliable alternative technique and
      has been used in Thailand for a few years. The ultrasound dilution technique is a
      noninvasive method to measure and monitor vascular access blood flow of patients
      receiving HD. There is no previous report about the evaluation of access blood
      flow in the buttonhole technique. OBJECTIVE: To measure vascular access blood
      flow by noninvasive ultrasound dilution in HD patients using the buttonhole
      technique for cannulation of AV needle to AVF and investigate the factors
      associated with impaired vascular access blood flow. MATERIAL AND METHOD: A cross
      sectional study evaluating HD patients using the buttonhole technique at the
      outpatient HD center of Rajavithi Hospital and National Kidney Foundation at the
      Priest Hospital in Thailand was performed. The blood flow rate of AVF was
      measured by the ultrasound dilution technique. After starting HD with cannulated
      AV needle to AVF by the buttonhole technique and increasing dialyzer blood flow
      rate according to their HD prescription, measurements of blood flow of vascular
      access were evaluated within the first hour of the HD session by 2 consecutive
      measurements. RESULTS: A total of sixty eight HD patients were recruited. All
      patients had functioning AVF and received an adequate dialysis delivery dose, but
      14.7% of them had impaired access blood flow. The average access flow rate was
      1,326 +/- 858.8 ml/min. The average access flow rate of patients with good and
      impaired access flow rates was 1,497.8 +/- 812.4 and 330.0 +/- 135.0 ml/min. The
      factors associated with impaired access blood flow were old age, diabetes
      mellitus and dyslipidemia. CONCLUSION: This present study suggests that annual
      direct measurement of access blood flow as ultrasound dilution technique is an
      acceptable tool to screen AVF dysfunction, especially HD patients of old age,
      and/or with diabetes mellitus and dyslipidemia.

PMID- 22619890
TI  - N-terminal-pro-brain natriuretic peptide for the differential diagnosis of
      hypovolemia vs. euvolemia in hyponatremic patients.
AB  - BACKGROUND: Hyponatremia (serum sodium < 135 mEq/L) is the most common
      electrolyte abnormality in hospital and has impact on patient morbidity and
      mortality. The accuracy of volume status assessment is a major problem for the
      treatment planning especially to discriminate mild hypovolemic from euvolemic
      patients. OBJECTIVE: To examine the relationship between plasma N-Terminal-pro
      Brain Natriuretic Peptide (NT-pro-BNP) level and extracellular water (ECW) status
      during the treatment of hyponatremia, as well as the cut-off value of plasma NT
      pro-BNP in the differential diagnosis of volume status in hypovolemic vs.
      euvolemic hyponatremic patients. MATERIAL AND METHOD: Hyponatremic patients
      without clinical hypervolemia in Rajavithi Hospital were divided into the
      hypovolemic group and the euvolemic group according to ECW volume determined by
      bioimpedance analysis (BIA). Serum sodium, plasma NT-pro-BNP and ECW were
      assessed at the beginning, at the half correction of hyponatremia and at the end
      of treatment. RESULTS: Of the 26 patients, 18 (69.2%) were hypovolemic and 8
      (30.8%) were euvolemic. Before treatment, NT-pro-BNP levels of the patients with
      hypovolemia was significantly lower than the patients with euvolemia [median
      (min, max)] (pg/mL) of hypovolemic vs. euvolemic group [114 (21, 6,803) vs. 1,509
      (538, 8,541)] respectively (p < 0.001) and NT-pro-BNP levels change in the
      similar direction as ECW volume during the treatment. The best cut-off value of
      plasma NT-pro-BNP level to distinguish hypovolemic from euvolemic hyponatremia
      was 518 pg/ml with the sensitivity of 94.4% and the specificity of 100%.
      CONCLUSION: Plasma NT-pro-BNP levels provide objective information with
      respection to volume status in hyponatremia patients and can be used in clinical
      diagnosis of hypovolemic vs. euvolemic hyponatremic hyponatremia.

PMID- 22619891
TI  - Late dorsal tilt angulation of distal articular surface of radius in Colles' type
      of fracture at the end of the immobilization, can it be predicted?
AB  - BACKGROUND: The objective was to predict the late dorsal tilt angulation of
      distal articular surface of radius in Colles' type of fracture with radioulna
      index difference, age, sex of the patient and dorsal cortex comminution. MATERIAL
      AND METHOD: Correlation between previously mentioned factors and the changing
      degree of dorsal tilt angulation of distal articular surface of radius were
      analyzed. Sixty three wrist radiographs of sixty two patients with Colles' type
      of fracture were evaluated for dorsal tilt angulation of distal articular
      surface, radioulna index before and after reduction and at the end of the
      immobilization, dorsal cortex comminution after reduction. The interobserver and
      intraobserver generalizability coefficients of the dorsal cortex comminution
      measurement method were analyzed. RESULTS: Dorsal cortex comminution, age and sex
      of the patient were the predictors of the dorsal tilt angulation of distal
      articular surface of Colles' type of fracture at the end of the immobilization.
      Partial correlation coefficient for dorsal cortex comminution, age and sex were
      0.177, 0.201 and -8.206 respectively. The generalizability coefficients were
      rated as substantial to excellent. CONCLUSION: The late dorsal tilt angulation of
      distal articular surface of radius at the end of the immobilization can be
      predicted from size of dorsal cortex comminution, age and sex of the patients.

PMID- 22619892
TI  - The accuracy of 99m Tc-MIBI scintigraphy for preoperative parathyroid
      localization in primary and secondary-tertiary hyperparathyroidism.
AB  - OBJECTIVE: The aim of the present study was to assess the accuracy of
      preoperative parathyroid localization using double phase planar 99mTc
      methoxyisobutylisonitrile parathyroid scintigraphy (MIBI scintigraphy) in
      patients with primary hyperparathyroidism (pHPT) and secondary-tertiary
      hyperparathyroidism (stHPT) due to chronic renal failure. MATERIAL AND METHOD: A
      retrospective study was conducted. Between 1995 and 2010, seventy-one patients
      with hyperparathyroidism (mean age 47 +/- 15 years; range 14-84 years) underwent
      neck surgery; 18 with pHPT and 53 with stHPT. None of these patients had
      undergone previous neck surgery. Preoperative demographics, clinical and
      laboratory values, MIBI scintigraphy, operative findings, location, size and
      histopathological results of all abnormal parathyroid glands were recorded.
      RESULTS: The abnormal parathyroid gland excised from 18 pHPT patients included 11
      solitary adenoma (610%), 5 carcinoma (28%), 1 patient with single gland
      hyperplasia (6%) and 1 patient with two gland hyperplasia (6%). MIBI scintigraphy
      correctly laterized and localized 17 of 19 abnormal parathyroid glands with
      sensitivity 90%, specificity 100%, positive predictive value (PPV) 100% and
      accuracy 97.2%. The abnormal parathyroid glands excised from 53 stHPT patients
      included 48 patients with multiple hyperplasia (91%), 1 patient with single
      hyperplasia (2%), 1 patient with solitary adenoma (2%) and 3 patients with
      multiple adenomas (6%). MIBI scintigraphy correctly lateralized 116 of 173
      abnormal parathyroid glands with sensitivity 67.1%, specificity 92.3%, positive
      predictive value (PPV) 97.5% and accuracy 71.7%. Precise localization occurred in
      63.6% of the abnormal parathyroid glands. Significant differences were found with
      respect to age, intact parathyroid hormone, serum calcium, phosphorus, BUN levels
      between the pHPT and stHPT (p < 0.001). The average size of abnormal parathyroid
      glands in pHPT (2.28 +/- 1.05 cm) was greater than that of stHPT (1.56 +/- 0.58
      cm) with significant difference (p < 0.001). Surgical parathyroid size were
      significantly greater in MIBI true-positive glands (1.79 +/- 0.68 cm) compared to
      MIBI-false negative glands (1.29 +/- 0.52 cm) with significant difference (p <
      0.001). CONCLUSION: MIBI scintigraphy is very sensitive and highly accurate for
      pre-operative localization of parathyroid lesion in patients with pHPT So, it was
      useful for surgeons as a guide in the preoperative localization for performing
      unilateral surgery to reduce operating time and morbidity. In stHPT
      MIBIlscintigraphy appears fair sensitive and is not yet accurate to detect all
      abnormal parathyroid glands in multiple hyperplasia. So, it is not an essential
      prerequisite before surgery.

PMID- 22619893
TI  - Comparison of the accuracy of transvaginal sonography and hysteroscopy for the
      diagnosis of endometrial polyps at Rajavithi Hospital.
AB  - OBJECTIVE: To compare the accuracy of Transvaginal Sonography (TVS) and
      Hysteroscopic diagnosis (HD) for diagnosis of endometrial polyp diseases.
      MATERIAL AND METHOD: A retrospective study was conducted and based on the medical
      records of endometrial polyp patients who were submitted to histological
      diagnosis during January 1st, 2005-December 31st, 2010 at Rajavithi Hospital.
      Apart from histological findings which are final, all patients had been submitted
      to both TVS and HD tests. The statistical analysis considered
      percentage,sensitivity, specificity and accuracy and compared the accuracy
      effectiveness of TVS and HD. RESULTS: The present study examined sixty
      endometrial polyp patients who were women whose mean age was 31-40 years.
      Sensitivity,specificity and accuracy for diagnosis of endometrial polyps by TVS
      were 60%, 33.3% and 57.6%, respectively where as those by HD were 93.3%, 33.3%
      and 87.9%, respectively. The present study noted that the HD showed superior
      accuracy compared to TVS (P < 0.001) in the endometrial polyp diagnosis.
      CONCLUSION: Particularly, for endometrial polyp diagnosis, hysteroscope was more
      sensitive and accurate than transvaginal sonography

PMID- 22619894
TI  - Novel technique of mesh fixation with cyanoacrylate in totally extraperitoneal
      laparoscopic hernia repair: early experience.
AB  - Totally extraperitoneal laparoscopic hernioplasty (TEP) is an alternative surgery
      for inguinal hernia repair, but chronic pain is still a problem. The authors
      proposed the use of cyanoacrylate for mesh fixation instead of staples which
      might be the cause of chronic groin pain. The authors also innovated an
      instrument for delivery of cyanoacrylate for mesh fixation. The present article
      reported early experience in the first 15 patients who were treated with this
      technique. Early post-operative pain was comparable to a previous study, no
      recurrence and no chronic groin pain was detected after surgery.

PMID- 22619895
TI  - Quality of life, needs and the mode of coping of the health personnel at
      Naradhiwasrajanagarindra Hospital in terrorism influence area in Thailand.
AB  - The present study was to identify the quality of life (QOL), the needs of help
      and the mode of coping among the health personnel of Naradhiwasrajana garindra
      Hospital in a terrorism situation, the first research in Thailand. The chaos of
      separatist insurgency in the southern part of Thailand has been re-emerged since
      2004. The present study was seeking for ways the health personnel coped with the
      situation while their quality of life and needs that were affected how they had
      handled the events were explored. General questionnaire, quality of life rand 36
      SF-36 questionnaires, help seeking questionnaire and Mode of coping with the
      terrorism questionnaire were sent to all health personnel in the hospital in
      November 2007. 392 (65.3%) complete questionnaire were received from 600
      distributed papers. They were female 328 (83.7%) and male 64 (16.3%), at the age
      of 21-59 years old (the mean age of 39.05 SD +/- 9.82), with three different
      religions, Buddhist 269 (68.6%), Muslim 122 (31.1%) and Christian 1 (0.30%).
      Thirty nine responses (9.9%) had been directly exposed to a terrorist attack,
      while 353 responses (90.1%) had a family member or friends who had been exposed.
      The results revealed that the overall mean scores of QOL were 73.1 +/- SD 15.5.
      Mean scores of male were significantly lower than female in general health,
      social functioning and role-emotional subscales. QOL mean scores of those with no
      terrorism exposure were significantly higher than those with terrorism exposure
      in role-physical, social functioning and mental health subscales. The most need
      of help for the personnel was safety of life and belongings (30.6%) followed by
      the need of money (23.0%). To cope with the terrorist attack, people (81.7%)
      would always resort to religious beliefs (72.0%) talk it out with coworkers,
      friends about their feelings, and (68.7%) inquire about the safety of their
      families and friends after the incident. Certainly, terrorism affected QOL and
      the most need of people in violent areas was life safety which agrees with
      Maslow's hierarchy of needs.

PMID- 22619896
TI  - Reliability of visual acuity measurements taken with a notebook and a tablet
      computer in participants who were illiterate to Roman characters.
AB  - BACKGROUND: Electronic measurement of visual acuity (VA) has been proposed and
      adopted as a method of determining VA scores in clinical research. Characters
      (optotypes) are displayed on a monitor screen and the examinee selects a match
      and inputs his choice to another electronic device. Unfortunately, the optotypes,
      called Sloan letters, in the standard protocol are 10 Roman characters. This
      limits their practicabilityfor measuring VA of patients who are illiterate to
      these characters. The authors introduced a method of displaying the Sloan letters
      one by one on a notebook and all 10 Sloan letters on a tablet computer screen.
      The former is for testing the patients whereas the latter is for them to input
      their responses by tapping on a letter that matches the one on the notebook
      screen. OBJECTIVE: To assess test-retest reliability of VA scores determined with
      this method. MATERIAL AND METHOD: Participants without ocular abnormality were
      recruited to have their right eyes measured with the same VA measurement method
      twice, one week apart. Those who were illiterate to Roman characters were
      enrolled for the aforementioned method for measuring their VA (Tablet group). A
      15-inch display notebook computer and a 9-inch display tablet computer (iPad)
      communicated via a local wireless data network provided by a Wi-Fi router. Those
      who understood Roman characters were enrolled to have measurements with a 17-inch
      desktop computer and an infrared wireless keyboard (Keyboard group). Both methods
      used the same protocols and software for VA measurements. Reliability of VA
      scores obtained from each group was assessed by the confidence interval (CI) of
      the difference of the scores from the test and retest. The t test was used to
      analyze differences in mean VA scores between the test and retest in each group
      with p < 0.05 determined as statistically significant. RESULTS: There were 49 and
      50 participants in the Tablet and Keyboard group respectively. The 95% CI of the
      difference between the scores from the test and retest in each group was 2
      letters. Approximately 95% of participants in each group had an absolute
      difference of the scores between the test and retest of 7 letters. The mean of VA
      scores from the first test was significantly different from that of the second
      test in the Keyboard group (one-letter difference, p = 0.049); there was no
      significant difference between these scores in the Tablet group (0.1-letter
      difference, p = 0.86). CONCLUSION: Tablet computers may be used to assist
      patients who are illiterate to Roman characters in having their VA measured with
      the standard electronic protocol. This preliminary study suggested that the
      proposed method should be useful for reliable measuring VA outcome in multicenter
      international clinical trials without encountering a language barrier

PMID- 22619897
TI  - Role of adjuvant radiotherapy after radical hysterectomy in node-negative stage
      IB-IIA cervical cancer with intermediate risk factors.
AB  - OBJECTIVE: To assess the benefit of adjuvant radiotherapy after radical
      hysterectomy in node-negative FIGO stage IB-IIA cervical cancer patients with
      intermediate risk factors. MATERIAL AND METHOD: Medical records of FIGO stage IB
      IIA cervical cancer patients who underwent radical hysterectomy at Rajavithi
      Hospital between January 2000 and December 2007 with negative pelvic node were
      reviewed. Of the 573 node-negative stage IB-IIA cervical cancer patients, 115 had
      at least one of the intermediate risk factors; 18 cases received adjuvant
      radiotherapy (RT group) while 97 patients did not receive (non RT group).
      Recurrence-free survival and complications of combined treatment of each group
      were investigated. RESULTS: The median follow-up period was 62.5 months (range 5
      119 months). Of the 115 patients with any of the intermediate risk factors, 56
      (48. 7%) had single intermediate risk factor and 59 (51.3%) had two or more
      intermediate risk factors. Sixteen patients (13.9%) developed recurrence, 6 at
      the locoregional site, 5 at the distant sites and 5 at synchronous sites. Eleven
      patients (18.6%) who had two or more intermediate risk factors developed
      recurrences. In the RT group, 3 patients (20.0%) developed recurrences whereas 8
      patients (18.2%) in the non RT group developed recurrences (p = 0.574). The 5
      year recurrence free survival rates in patients with two or more risk factors
      received adjuvant radiotherapy and those without adjuvant radiotherapy were 77.8%
      and 83.0%, respectively (p = 0.904). No locoregional recurrence occurred in
      patients who received adjuvant radiotherapy. Three patients had treatment related
      complications (2 with leg lymphedema and 1 with radiation proctitis). CONCLUSION:
      Postoperative radiotherapy in node-negative stage IB-IIA cervical cancer patients
      with intermediate risk factors reduced only the incidence of locoregional
      recurrence. Distant recurrence was the major pattern of treatment failure after
      adjuvant radiotherapy.

PMID- 22619898
TI  - Survival rate of recurrent cervical carcinoma.
AB  - OBJECTIVE: To determine the survival rate of recurrent cervical carcinoma and
      clinical variables influencing survival. MATERIAL AND METHOD: Eighty eligible
      patients with recurrent cervical carcinoma were identified from the tumor
      registry record of gynecologic oncology division, Rajavithi Hospital between
      January 2004-December 2010. The pathological and clinical data were retrospective
      reviewed. Numerous clinical variables were analyzed including age,
      histopathology, primary staging, site of recurrence, complete treatment time to
      recurrence and initial treatment after recurrence. RESULTS: Among the 80
      patients, mean age of the patients were 48.11 years (SD = 9.62). Median time from
      complete primary treatment to recurrence was 11.7 months. Fifty four cases
      (67.5%) were squamous cell carcinoma and the others were nonsquamous cell
      carcinoma. Seventy two cases (90.1%) were previously treated with radiation
      therapy. Sixty six cases (82.5%) had only pelvic recurrence without distant
      disease. Median follow-up period of the present study was 14.2 months. Two-year
      survival rate of the group was 33.7%, median survival was 15.4 months. Two years
      survival rate of the patients received surgery, radiation, chemotherapy and
      supportive only as initial treatment after recurrence were 43.6%, 53.3%, 18.1%
      and 25.0%, respectively. Whereas median survival of the patients received
      surgery, radiation, chemotherapy and supportive only as initial treatment after
      recurrence were 20.7, 24.5, 11.4 and 10.8 months respectively. Site of recurrent
      and type of initial treatment modality after recurrence had statistic
      significance in multivariable analysis (p = 0.001 and p = 0.026, respectively).
      CONCLUSION: Survival rate of recurrent cervical carcinoma was poor Surgery and
      radiation as initial treatment modality after recurrence may have survival
      benefit in well selected patients.

PMID- 22619899
TI  - Cerebral tuberculoma presented as primary malignant brain tumor: a case report.
AB  - A 62 year-old Thai man presented symptoms of chronic progressive headache for
      nearly one year and left side ataxia for two weeks. MRI brain suggested a primary
      malignant brain tumor with moderate hydrocephalus. Total removal of the lesion
      was performed. The histopathological report was caseating granulomatous
      inflammation involving cerebellar parenchyma; suggestive of tuberculoma, PCR for
      M. Tuberculosis complex, using brain tissue from formalin-fixed paraffin-embeded
      block, yields positive result for M. Tuberculosis complex. He was treated with
      antituberculous drugs.

PMID- 22619900
TI  - Vitamin E ameliorates renal fibrosis by inhibition of TGF-beta/Smad2/3 signaling
      pathway in UUO mice.
AB  - BACKGROUND: One striking feature of chronic kidney disease (CKD) is tubular
      atrophy and interstitial fibrosis (TA/IF). During chronic renal injury,
      transforming growth factor-beta (TGF-beta) is involved in this process causing
      progression of renal fibrosis. Smad2/3 proteins have been identified to have an
      important function in the expression of extracellular matrix (ECM) regulation
      through TGF-beta signaling pathway. In the present study, the authors
      investigated the effect of vitamin E on renal fibrosis in mice model of
      unilateral ureteral obstruction (UUO). MATERIAL AND METHOD: UUO or sham-operated
      mice were randomly assigned to receive vitamin E (alpha tocopherol) or placebo
      and were sacrificed on days 3, 7 and 14 after UUO or sham operation. Kidney
      specimens were fixed for pathological study and immunohistochemistry for TGF
      beta1. Protein expression of TGF-beta1 and Smad2/3 was determined by western blot
      analysis. The mRNA expression of TGF-beta1 was measured by real-time RT-PCR.
      RESULTS: Vitamin E treated UUO mice had less severity of renal fibrosis than
      placebo treatment. TA/IF was significantly attenuated by vitamin E treatment.
      Immunohistochemistry revealed increasing of TGF-beta1 protein expression in the
      interstitium area of obstructed kidneys. Moreover increasing of TGF-beta1 protein
      and upregulation of TGF-beta1 mRNA in UUO mice were confirmed by western blot and
      real time RT-PCR. In contrast, vitamin E treatment significantly inhibited the
      expression of TGF-beta1 protein and mRNA in UUO mice compared with placebo
      treatment. Interestingly, Smad2/3 protein expression became progressive
      increasing in UUO mice on day 3, 7 and 14 compared with sham controls. The
      expression of Smad2/3 protein was significantly lower in vitamin E treated UUO
      mice than placebo treatment in any time points. CONCLUSION: Vitamin E treatment
      attenuated the progression of renal fibrosis in obstructed kidneys. The
      renoprotective effect of vitamin E could be mediated by inhibition of TGF
      beta/Smad2/3 signaling pathway.

PMID- 22619901
TI  - Vitamin E ameliorates renal fibrosis in ureteral obstruction: role of maintaining
      BMP-7 during epithelial-to-mesenchymal transition.
AB  - BACKGROUND: Epithelial to mesenchymal transition (EMT) is a process which tubular
      epithelial cells (TEC) undergo a phenotypic conversion to the matrix-producing
      fibroblasts and myofibroblasts. Phenotypic alteration of TEC was induced by the
      important cytokine transforming growth factor-beta (TGF-beta) to development of
      renal fibrosis. However bone morphogenetic protein-7 (BMP-7) generally
      counteracts with TGF-beta to maintenance of epithelial phenotype. In the present
      study, the authors investigated the anti-fibrotic property of vitamin E on
      unilateral ureteral obstruction (UUO) model mice. MATERIAL AND METHOD: UUO or
      sham-operated mice were randomly assigned to receive vitamin E (alpha tocopherol)
      or placebo and were sacrificed on days 3, 7 and 14 after operation. Kidney
      specimens were fixed for pathological study and immunohistochemistry for BMP-7.
      Protein expression of BMP-7 was determined by western blot analysis. The mRNA
      expression of BMP-7 and TGF-beta1 were measured by real-time RT-PCR. RESULTS:
      Vitamin E treated UUO mice showed the less severity of renal fibrosis. Tubular
      atrophy and interstitial fibrosis were significantly attenuated in vitamin E
      treatment. Immunohistochemistry revealed decreasing of BMP-7 protein expression
      in cytoplasm of TEC in obstructed kidneys. Moreover decreasing of BMP-7 protein
      and downregulation of BMP-7 mRNA in UUO mice were confirmed by western blot and
      real time RT-PCR. In contrast, vitamin E treatment significantly maintained the
      expression of BMP-7 protein and mRNA in UUO mice compared with placebo treatment.
      On the other hand, TGF-beta1 mRNA expression showed progressive upregulation in
      UUO mice on day 3, 7 and 14 compared with sham controls. The expression of TGF
      beta1 mRNA was significantly lower in all vitamin E treated UUO mice compared
      with placebo treatment. CONCLUSION: Vitamin E treatment attenuated the
      progression of renal fibrosis in obstructed kidney by inhibited the TGF-beta1 but
      maintained the BMP-7 during EMT. Thus, the renoprotective effects of vitamin E
      could have some therapeutic value to inhibit the progression of renal fibrosis in
      human.

PMID- 22619902
TI  - Prevalence of malnutrition and nutritional assessment in abdominal-surgical
      patients; a prospective cross-sectional study.
AB  - OBJECTIVE: Nutritional intervention is important in abdominal-surgical patients.
      The primary objective was to determine the prevalence of malnutrition in
      abdominal-surgical patients. The secondary objectives were to determine the rate
      of nutritional assessment and the association of malnutrition to postoperative
      complications. MATERIAL AND METHOD: 106 elective abdominal-surgical patients at
      Thammasat hospital from September 2008 to February 2010 were assessed
      preoperatively by independent research assistant using ESPEN criteria for
      preoperative nutritional support as diagnostic criteria. The rate of nutritional
      assessment that had been done to these 106 patients by their responsible
      physicians was also determined using medical records and patients' interview by
      research assistant. Severe malnutritional patients according to ESPEN criteria
      that were not been assessed preoperatively by their responsible physicians about
      nutritional status were compared between benign and malignant group. The
      association of malnutrition to postoperative complications was also analyzed with
      adjusting for other confounding factors. RESULTS: 29 patients (27%) of 106
      abdominal-surgical patients had malnutrition. The prevalence of malnutrition was
      significant higher inpatient with malignancy (18 from 31; 58%) than inpatient
      with benign diseases (11 from 75; 15%) with p-value less than 0.001. The rate of
      nutritional assessment by their responsible physicians (Benign 14 from 75; 19%
      vs. Malignant 24 from 31; 77%; p < 0.001) and severe malnutrition patients that
      had not been assessed by their responsible physicians (Benign 9 from 11; 82% vs.
      Malignant 2 from 18; 11%; p < 0.001) were significantly different. After
      adjusting for other confounding factors, malnutrition was significantly
      associated with postoperative complications with odds ratio of 3 and 95% CI of
      1.1, and 8.4. CONCLUSION: Malnutrition is common in abdominal-surgical patients.
      Routine preoperative nutritional assessment in this type of patients is
      recommended.

PMID- 22619903
TI  - Viral infection of central nervous system in children: one year prospective
      study.
AB  - Viral infection of central nervous system (CNS) is a common problem worldwide,
      especially in children. The clinical manifestations of viral CNS infection are
      the most important clues for diagnosis and treatment. The 1-year prospective
      study to explore the prevalence, clinical manifestations, and laboratory findings
      of viral CNS infection in children, including human herpes virus (HHV) type 1, 2,
      3, 4, 5, 6A, 6B, 7, enterovirus B, mumps virus, measles virus, Japanese
      encephalitis virus, JC virus, BK polyomavirus, Nipha virus and influenza virus
      (H1N1, H3N2) were performed. Total of 71 children suspected CNS infection, aged
      between 2 days to 12.9 years were enrolled from May 2009 to April 2010. Total 4
      children with non CNS infection, 5 bacterial meningitis, 2 tuberculous meningitis
      CNS infection were excluded. The HHV2 (50.0%) was the most common viral CNS
      infection. Other viral CNS infection included HHV1 (11.60%), VZV (6.7%), HHV6
      (3.3%), HHV7 (3.3%), enterovirus B (1.67%) and H3N2 (1.67%). Diarrhea,
      irritability and CSF pleocytosis may helpful for differentiation between subtype
      of viral CNS infection.

PMID- 22619904
TI  - Effect of polyethylene bag to prevent heat loss in preterm infants at birth: a
      randomized controlled trial.
AB  - BACKGROUND: Hypothermia at birth has been associated with increased morbidity and
      mortality in preterm infants. OBJECTIVE: To evaluate the effect of wrap with
      polyethylene bag at birth on admission temperatures and the incidences of
      hypothermia on admission in preterm infants gestational age < or = 32 weeks.
      MATERIAL AND METHOD: A randomized controlled trial was conducted in thirty-eight
      preterm infants with gestational age < or = 32 weeks. The infants were assigned
      and placed in polyethylene bag immediately after birth without drying under a
      radiant warmer or received standard thermal care including being dried and placed
      under a radiant warmer. Rectal temperatures were recorded on admission to
      neonatal unit and incidences o hypothermia were compared between the two groups.
      RESULTS: The body temperatures of preterm infants with polyethylene bag were
      significantly higher than those of the control group {median 36.5 degrees C
      (range 35.5 degrees C-37.2 degrees C) vs. 35.9 degrees C (range 34.9 degrees C
      36.5 degrees C), p < 0.001}. On admission, the incidence of hypothermia in
      preterm infants wrap with polyethylene bag was significantly lower than in the
      control group (26% vs. 89%, p < 0.001) with a risk reduction of 0.63 (95% CI 0.39
      0.87) and a number needed to treat of 1.58. CONCLUSION: Polyethylene bag prevents
      heat loss at delivery in preterm infant less than 32 weeks gestation. Incidence
      of hypothermia was significantly reduced by use of polyethylene bag, a simple and
      inexpensive intervention.

PMID- 22619905
TI  - Henoch-Schonlein purpura in Thai children: a report from single center.
AB  - Henoch Schonlein Purpura (HSP) is the most common vasculitis in childhood. It is
      a self-limited disease. Recurrent HSP is not uncommon. Colchicine, an anti
      inflammatory drug, has been used in prolonged HSP in only a few patients with
      good response. The present study described pediatric HSP patients in a single
      center, Thailand. To determine the epidemiology, clinical manifestations,
      treatments, and outcomes of HSP patients, the authors retrospectively studied 26
      patients (age < 15 years) diagnosed with HSP at Thammasat University Hospital,
      from January 01, 2004 through December 31, 2010. The mean age was 7.2 +/- 3.8
      years; median (range) follow-up was 2 (0.5-39) months. Fifteen (57.7%) patients
      were female. Clinical manifestations were skin (100%), joint (69.2%),
      gastrointestinal symptoms (50%) and renal involvement (19.2%). Symptoms lasted
      within 8 weeks in 21 (80%) patients. Recurrences identified in 5 (19%) patients
      with a mean of 4.8 +/- 2.4 times. The clinical outcome was excellent without
      major complication. Colchicine induced remission of severe and recurrent
      petechiae in one patient who developed methemoglobinemia after dapsone therapy.
      Colchicine may be an effective drug for prolonged HSP without renal involvement.
      The controlled studies to establish benefit effect and optimal regimen of
      colchicine in HSP is required.

PMID- 22619906
TI  - A 1-year experience with liquid-based and conventional papanicolaou smear in
      Thammasat University Hospital.
AB  - OBJECTIVE: The aim of the present study was to evaluate the prevalence of
      abnormal Pap smears as detected by liquid-based (LBP) and conventional (CPP)
      techniques in women who were patients in the gynecologic clinic, Thammasat
      University Hospital. MATERIAL AND METHOD: Retrospective analysis of cervical
      cancer screening, histopathological findings and operative procedures was done
      between January 2009 and December 2009. Of the 6,332 participants who underwent
      gynecological examination and cervical screening and had a Pap smear result as
      atypical squamous cells of undetermined significance or worse would be performed
      a further colposcopic examination. RESULTS: A total of 6,332 women were screened
      for cervical cancer in the one year period. A total of 169 abnormal Pap smears
      were found. Of 497 (8%) and 5,835 (92%) women were screened by LBP and CPP,
      respectively. The mean age of patients was 39.45 years old (14-90) and 1,550
      (24.5%) women were post menopausal. The Prevalence of abnormal Pap smears was 4.0
      and 2.6% in the LBP and CPP groups, respectively. Among LBP group, patients with
      atypical smear and LSIL (low grade squamous intraepithelial lesion) were 11
      (2.29%) and 9 (1.8%), respectively. While CPP group, patient with atypical smear,
      LSIL, HSIL (high grade squamous intraepithelial lesion) and cancer were 73
      (1.25%), 49 (0.84%), 25 (0.43%) and 2 (0.03%), respectively. CONCLUSION: The
      prevalence of abnormal Pap smear in women who attended gynecologic clinic of
      Thammasat University Hospital was 4.0% and 2.6 % per LBP and CPP group,
      respectively. There was no significant difference in the incidence of atypical
      smear and false positive result between LBP and CPP.

PMID- 22619907
TI  - Effect of intramuscular diclofenac after explore laparotomy for gynecologic
      surgery: a randomized double-blinded placebo controlled trial.
AB  - BACKGROUND: Several adjuvant analgesic agents proposed to treat the postoperative
      pain while reducing the doses of opioid and its derivatives. Non-steroidal anti
      inflammatory drugs (NSAIDs) are widely used in several operative procedures. The
      present study aimed to demonstrate the morphine-sparing effects of single-dose
      intramuscular diclofenac sodium in explore laparotomy gynecologic surgery.
      MATERIAL AND METHOD: Forty-six patients were randomly assigned to receive 75-mg
      of diclofenac sodium or normal saline with intramuscular morphine during
      immediate postoperative period. Additional morphine for pain control was given by
      patient-controlled analgesia. 24-hour morphine consumption, pain score, adverse
      effects and satisfaction of the patients were recorded. RESULTS: Median morphine
      consumption among groups was significant difference between placebo and
      diclofenac group (32 and 19 mg) (p = 0.041). Greater difference was shown in
      patients who underwent total abdominal hysterectomy (p = 0.009). Catagorical pain
      score at 6-hour postoperatively was significant lower in diclofenac group (p =
      0.006). No significant difference was found between groups in visual analogue
      pain score, patients' satisfaction, presence of bleeding or nausea and vomiting.
      CONCLUSION: The present study demonstrated that single dose of diclofenac sodium
      has morphine-sparing effects and can be safely used in explore laparotomy
      gynecologic surgery without significant adverse effects.

PMID- 22619908
TI  - Comparison of level of pain between using manual vacuum aspiration and sharp
      curettage in management of abnormal uterine bleeding.
AB  - OBJECTIVE: To compare the level of pain between using manual vacuum aspiration
      and sharp curettage in the patients who had abnormal uterine bleeding that
      underwent uterine curettage under paracervical block with analgesics. DESIGN:
      Randomized controlled trial study. MATERIAL AND METHOD: Between September 2009 to
      June 2010, 48 women with abnormal uterine bleeding who need to undergone uterine
      curettage were asked to join the present study and informed consents were signed.
      Twenty four women were randomly assigned into manual vacuum aspiration (MVA)
      group and other 24 women into sharp curettage group. The main outcome was the
      difference of the level of pain before, during and after procedure measured by
      using the visual analog scale and categorical pain scores. Fisher exact, Student
      t test and Mann-Whitney U test were used for statistical analysis. RESULTS: The
      median visual analog score during MVA-procedure was significantly lower than the
      median visual analog score during in sharp curettage (median visual analog pain
      scores (interquartile range) 80 (30-100) vs. 45 (0-80); p < 0.01)). And the
      median score immediately after procedure in the MVA group was also significantly
      lower than in the sharp curettage group (median visual analog pain scores
      (interquartile range) 45 (0-80 vs. 25 (0-70); p = 0.02). The categorical pain
      score in the MVA group during procedure and immediately after procedure were also
      significantly lower than in the sharp curettage group. (No pain to mild pain vs.
      moderated to severe pain; p = 0.03, immediately after procedure: no pain to mild
      pain vs. moderated to severe pain; p = 0.01). CONCLUSION: The level of pain in
      the patients who underwent uterine curettage by using MVA was lower than using
      sharp curettage. The using MVA may reduce pain compared to sharp curettage.
      However, more sample size research should be conducted to determine this
      significant.

PMID- 22619909
TI  - Clinical experience in forearm tourniquet use.
AB  - OBJECTIVE: To assess the efficacy and complications of forearm tourniquet
      application in minor hand and wrist surgeries those use local anesthesia.
      MATERIAL AND METHOD: A series of ninety-three patients underwent various kinds of
      hand and wrist surgery using forearm tourniquet performed by senior author (SN)
      at Thammasat University hospital in the last 5 years was collected. The
      tourniquet was applied at proximal forearm with 250 mm Hg pressure. The surgical
      tourniquet time tolerated by the patients, postoperative complications, and
      effectiveness for the surgeon to perform the surgery were collected and analyzed.
      RESULTS: The forearm tourniquet provided bloodless field in all operations. All
      patients could tolerate forearm tourniquet up to 80 minutes (average 27 minutes).
      None of the patients had complications related to tourniquet uses after surgery.
      CONCLUSION: Using forearm tourniquet in minor hand and wrist surgery is
      effective, helpful, and safe.

PMID- 22619910
TI  - Hallux valgus correction using a Mini TighTrope device: a report of the short
      term outcomes in 3 feet.
AB  - OBJECTIVE: Bony works seems to be base procedure for hallux valgus correction.
      Due to the challenge and possible complications of these procedures, these issues
      generate 'Foot and Ankle Society' to consider alternative procedures. The 'Mini
      TightRope' (Arthrex, Inc., Naples, FL) or interrosseous suture/button device was
      introduced in 2007 to address the above mentioned point. Although its feasibility
      and utilization were attractive, some reports revealed its drawbacks and
      limitations. The present report is to demonstrate short-term outcomes and
      information that might be useful for avoidance of potential complications from
      application of this device. MATERIAL AND METHOD: Three involved-feet in 2
      patients with recalcitrant conditions and progressive hallux valgus, with at
      least a 6-month course of conservative treatment, were included. Limitation
      criteria for using 'Mini TightRope' were; non-athletic demand, good bone-stock,
      moderate severity of their hallux valgus (hallux-valgus-angle (HVA): 30-40,
      intermetatarsal-angle (IMA): 14-20), no hypermobility of first tarsometatarsal
      joint, and no signs of degenerative joint disease of first
      metatarsophalangeal/tarsometatarsal joint. Baseline data, American-Orthopaedic
      Foot-and-Ankle-Society (AOFAS) scores, Visual-Analogue-Scale Foot-and-Ankle (VAS
      FA) scores (including radiographic parameters) were collected at pre- and post
      operative periods. The operations were carried out by a single surgeon. Precision
      in the creation of the interosseous-tunnel between 1st-2nd metatarsals was
      critical for this device. All patients strictly followed a similar postoperative
      protocol, with austere prohibition of premature weight-bearing at forefoot-and
      midfoot areas in 1-month postoperative-period. RESULTS: Although pre
      postoperative (6-month) AOFAS/VAS-FA scores and radiographic angular differences
      were nonsignificant as to p-value: 0.10, there were satisfactory improvements of
      all scores and angular values in all postoperative periods. Patient number-two
      reported some tightness at 1st-2nd intermetatarsal area on left-foot. This was
      controlled with oral-medications in 1-month postoperative-period. Besides, there
      were no significant complications in the present report. CONCLUSION: 'Mini
      TightRope' might be of merit in hallux valgus correction for well-selected
      patients provided that technical implementation is precise and postoperative
      protocol is followed with proper discipline.

PMID- 22619911
TI  - Characteristics of unscheduled emergency department return visit patients within
      48 hours in Thammasat University Hospital.
AB  - BACKGROUND: Auditing the return visit charts of patients who returned within 48
      hours is a very important method of quality assurance. Several factors can be
      possible causes of unscheduled emergency return visits. Therefore, identifying
      these factors is critical to decreasing the number of unnecessary visits in this
      group. OBJECTIVE: To determine rate, common initial presentation and cause of
      unscheduled emergency department return visits within 48 hours at Thammasat
      University Hospital. MATERIAL AND METHOD: The present study design involves
      retrospective observational study of patients who returned to the Emergency
      department (ED) within 48 hours after being discharged from the ED. Data was
      collected from August 1, 2009 to July 31, 2010. Patient age, gender triage level,
      patient-in time, patient-out time, length of stay, chief complaint, first and
      second visit diagnoses and disposition after second visit were recorded by chart
      review. The factors and causes of revisits were classified by the author as
      illness-related, patient-related, doctor-related and/or healthcare system
      related. RESULTS: A total of 307 (0.92%) patients returned visit to the ED within
      48 hours during August 1, 2009 to July 31, 2010. The most common chief complaint
      were dyspnea (75 cases or 24.4%), abdominal pain (53 cases or 17.3%), bleeding
      per vagina (28 cases or 9.1%). The rates of revisit that were related to factors
      of illness, patients, doctors and healthcare system were 60.6, 8.5, 28.3 and 2.6,
      respectively. Chi-squared was used for categorical data. CONCLUSION: Unscheduled
      ED return visit patients represent high risk patients. Patients in this group are
      associated with various factors. The present study indicates that the most common
      factor behind return visits were illness-related. Illness-related and patient
      related factors were significantly associated with discharged patient.
      Observational units could reduce unnecessary return visit in this group. Doctor
      related and healthcare-related factors were significantly associated with
      admitted return visit patients. Emergency physician training system and guideline
      implementation for doctors could reduce unexpected early discharge in this group.

PMID- 22619912
TI  - Correlation between stressors and academic performance in second year medical
      students.
AB  - OBJECTIVE: The present study aimed to find which type of stressors correlating to
      academic performance in second year medical students. One-hundred and eighty
      three second year medical students of Thammasat University participated in a
      three-week cross-sectional study. The self-report questionnaire consisted of Thai
      stress test, stress factors and examination grades referring academic performance
      were applied in the present study. RESULTS: Females felt stress more than males
      in severe, high, and medium level of stress. There was no low level of stress and
      no correlation between stress level and the entrance programs. Academic
      performance found relating to 1) fear of doing a mistake, 2) feeling of
      competition or comparison, 3) unilateral headache, 4) worrying, and 5) poor
      concentration. Students with poor concentration had significantly decreasing
      grade in the second year (p < 0.01). Interestingly, worrying, feeling of
      competition or comparison, and fear of doing a mistake correlated to increasing
      grade in some terms (p < 0.05). Specifically to poor concentration, there were
      medium linear association with fatigue, poor memory, feeling confused, feeling
      sad, feeling angry or irritable, changing appetite, and headache from stress (p <
      0.01). CONCLUSION: Poor concentration was the only stressor significantly
      correlated with poorer academic performance. Poor concentration also correlated
      with physical, cognitive, and financial problems. The recommendation is to keep
      watching those issues in order to early detect problem about academic
      performance.

PMID- 22619913
TI  - Parenting, parent and child mental health in the families of maltreated children
      registered with the Child Protection Unit, Thammasat University Hospital.
AB  - BACKGROUND: Mental health outcomes of maltreated children can be various. There
      are mediated by several factors including parental and family variables. Less is
      known in Thailand on how these variables and children's mental health are
      related. OBJECTIVE: To study mental health of the maltreated children and their
      parents and to examine the relationships between parent mental health, parenting
      behaviors, family function and child mental health. MATERIAL AND METHOD: A sample
      of 48 parents who contacted mental health service via the child protection unit
      from October 2009 to 2010 was recruited in this cross-sectional study. Child
      mental health, parent mental health, parenting behaviors and family functions
      were measured by the Strength and Difficulties Questionnaires--parent version,
      General Health Questionaire-28, the Conflict Tactic Scale parent-child version
      and Chulalongkorn Family Inventory, respectively. Chi-square test was conducted
      to explore the associations between each independent variable and child mental
      health. RESULTS: Thirty-eight point six percent of the children and 56.8% of the
      parents had mental health problems. Poor family function (OR = 24.6; 95% CI =
      2.8, 219.1) and negative parental behaviors (OR = 5.9; 95% CI = 1.3, 26.3) had
      statistically significant relationships with child mental health problem.
      CONCLUSION: Mental health problems were prevalent among the maltreated children
      and their parents. Parent training programs focusing on positive parenting
      strategies and enhancing family function may be beneficial to maltreated children
      and their parents in order to improve their mental health.

PMID- 22619914
TI  - Psychotherapy practices and training experiences: a national survey of young Thai
      psychiatrists.
AB  - OBJECTIVE: To survey the psychotherapy practices among young Thai psychiatrists,
      including perceptions pertaining to training experience and satisfaction of
      psychotherapy supervision. MATERIAL AND METHOD: The present study employed a
      cross-sectional descriptive survey. The sample consisted of all psychiatrists
      aged 40 years old or under. A questionnaire was developed by the research team
      and mailed to 142 young psychiatrists. RESULTS: There were 82 responders (57.7%
      response rate). The majority of the responding psychiatrists (80.5%) expressed
      their willingness to perform psychotherapy, however 57 of them (69.6%) were
      actually practicing it for 4 hours or less per month. Additionally, 41.5% had no
      self-confidence in using psychological interventions. The common barriers to
      practicing psychotherapy reported were lack of time to practice (85.4%), and no
      psychotherapy advisor (54.9%). Regarding psychotherapy training experience, 67.1%
      indicated that the training was sufficient. Types of psychotherapy training that
      young psychiatrists had received the most were supportive psychotherapy, Satir's
      systemic psychotherapy and cognitive behavioral therapy, respectively. The main
      factor affecting specific psychotherapy training experiences was the difference
      in the availability of training courses offered between the institutes. In
      regards to perceptions of psychotherapy supervision, 72.0% of the sample
      satisfied with psychotherapy supervision, although they had received an average
      of 4.8 hours per month only. CONCLUSION: Most of young Thai psychiatrists showed
      positive attitude to psychotherapy, and also preferred further training. However
      they performed psychotherapy in their work only a few hours per month due to
      heavy workloads, no supervisor and lack of confidence. The findings may have
      implications for individuals who are interested in the improvement of the quality
      and standard of the residency training program.

PMID- 22619915
TI  - Etiology of vertigo in Thai patients at Thammasat Hospital.
AB  - The purpose of this research is to study the causes of vertigo in the patients at
      Otoneurology Clinic, Thammasat Hospital. The data of these patients, collected
      from the medical records between January 2010 and January 2011, were reviewed and
      analyzed. From one hundred and forty-nine cases, 49 cases (33%) were men and 100
      cases (67%) were women, which yielded the male-to-female ratio of 1:2. The
      average age of patients was 55 year olds. The most common diagnostic category was
      peripheral vestibular disorders (80.5%). Other causes were central vestibular
      disorders (4.7%) and non-vestibular related (4%), whereas the remaining (10.1%)
      was undiagnosed. The causes of vertigo included benign paroxysmal positional
      vertigo: BPPV (53%), Meniere's disease (10.1%) and recurrent vestibulopathy
      (8.1%), while the underlying diseases found were diabetes mellitus (11.4%),
      hypertension (32.2%) and dyslipidemia (34.2%). In Otoneurology Clinic, Thammasat
      Hospital, the peripheral vestibular disorders was the main etiology of vertigo,
      while the three most common causes were BPPV Meniere's disease, and recurrent
      vestibulopathy respectively.

PMID- 22619916
TI  - Hep 88 mAB induced ultrastructural alteration through apoptosis like program cell
      death in hepatocellular carcinoma.
AB  - Hep88 mAbs, a novel monoclonal antibodies against hepatocellular carcinoma cell
      line from Thai patient, has been proved earlier for its tumoricidal effect on
      HepG2 cell line. In the present study, we investigated not only Hep88 mAb's
      targeted proteins from HepG2 cell line by western blot analysis but also its
      inhibitory activity on those cells by MTT assay. Moreover the ultrastructural
      alteration induced by Hep88 mAb of HepG2 cell line compare with Chang liver cell
      line was also examined. The results demonstrated that Hep88 mAb had cytotoxic
      effect on HepG2 cell line but not Chang liver cell line. Additionally,
      recognizing proteins against Hep88 mAb have been found on both cell lines. The
      ultrastructural alteration detected from transmission electron microscopy
      included the appearing of intracellular vacuolization as well as the dilatation
      of endoplasmic reticulum and mitochondria have been observed. These findings are
      suggested that the death of HepG2 cell line after treatment with Hep88 mAb might
      be involved by an apoptosis-like program cell death (PCD) pathway. From all of
      these remarks, it is possible that Hep88 mAb can injure HCC cells by binding with
      its membrane-bound antigen and activated downstream intracellular signals which
      is finally leading cell to be death via apoptosis-like PCD.

PMID- 22619917
TI  - Antimicrobial activity of rice bran extracts for diarrheal disease.
AB  - BACKGROUND: Rice bran showed antioxidative, antimutagenic, carcinogenic and
      antibacterial activities in previous reports. The rice bran has been recently
      used as a natural source of health food for several diseases such as diabetes,
      atherosclerosis and cancer. Severe diarrheal disease due to food-borne
      contamination of bacteria resulted from the bacteria have become resistant to
      many antibiotics. Hence, early treatment of diarrhea using natural food
      containing antibacterial activity to prevent progression of severe symptoms will
      be beneficial. OBJECTIVE: To investigate antimicrobial activity of rice bran
      extracts against bacteria causing diarrheal disease. MATERIAL AND METHOD:
      Bacterial strains isolated from patients include Vibrio cholerae, Vibrio
      vulnificus, Salmonella spp, Shigella spp, Escherichia coli (ETEC, EHEC, EAEC,
      EPEC, EIEC) and Stahylococcus aureus. Rice bran was extracted by five different
      extraction techniques. The antimicrobial activity was performed by disk diffusion
      and broth dilution methods. RESULTS: The results showed that rice bran extracts
      using different techniques of extraction were able to inhibit the growth of test
      strains. Rice bran extracts exhibited the most effective antibacterial activity
      against V. cholerae O139 with MIC value of 0.976 mg/ml. Using ethanol and
      supercritical techniques, Sang-Yod rice bran showed better antibacterial activity
      than Jasmine rice bran. In the present study, the MIC values of rice bran
      extracts against all tested strains except V. cholerae O139 and S. aureus were
      between 7.812 to 31.25 mg/ml. CONCLUSION: The results of present study provide
      insighful basic knowledge which would lead to develop rice bran extracts for
      effective treatment of diarrheal disease causing by bacteria including resistant
      strains. The rice bran extracts used against bacterial infection will be an
      alternative remedy in order to reduce the incidence of antibiotic resistance in
      future.

PMID- 22619918
TI  - Phenolic and flavonoid contents of Thai rice extracts and their correlation with
      antioxidant activities using chemical and cell assays.
AB  - BACKGROUND: Free radicals induce oxidative stress in various cell components,
      leading to certain diseases. Plant-derived antioxidants have become a profitable
      alternative to prevent oxidative stress in cells due to adverse effects of some
      synthetic antioxidants. OBJECTIVE: To determine the total phenolic and flavonoid
      contents and to evaluate the correlation between these two compounds and their
      antioxidant properties in the ethanolic extracts of brown rice and rice bran from
      Thai rice cultivars: Sangyod red rice and Dawk Mali 105 white rice using the
      chemical and cell assays. MATERIAL AND METHOD: Total phenolic and flavonoid
      contents in all of the rice ethanolic extracts were determined using the
      colorimetric assays, as well as their antioxidant activity was analyzed through
      two chemical assays: DPPH radical-scavenging and inhibition of lipid peroxidation
      assays, as well as through a cell-based assay: scavenging capacity against
      intracellular superoxide in cells using DCF. RESULTS: All the rice extracts
      displayed their antioxidant activities in a dose dependent manner through
      different assays, which were expressed as EC50 values. The DPPH scavenging assay
      revealed very high scavenging activity in both Sangyod brown rice and rice bran
      extracts. Positive correlations between this activity and total phenolic and
      flavonoid contents suggest the major free radical scavenging activity of such
      compounds. In contrast, the ethanolic extract of Sangyod rice bran exhibited non
      significant anti-lipid peroxidation activity relative to that of Sangyod brown
      rice and Dawk Mali 105 rice bran. Phenolic content was correlated to some extent
      with anti-lipid peroxidation activity, whereas flavonoid content and such
      activity showed a relatively weak correlation. Importantly, the cell-based assay
      also detected potent scavenging activity against superoxide production in HL-60
      cells pretreated with Sangyod extracts. The content of phenolics was a major
      contributor to this scavenging activity including that of flavonoids but to a
      lesser extent. CONCLUSION: These findings suggest that ethanolic extracts of
      brown rice and rice bran of Sangyod red rice can be promising sources of
      potential natural antioxidants.

PMID- 22619919
TI  - Crocodylus siamensis serum and macrophage phagocytic activity.
AB  - Antimicrobial activity of sera from many crocodilian species has been recognized.
      This activity was proposed to be mediated, at least in part, by complement. Due
      to the fact that complement proteins have different functions in the immune
      system, they may be involved in phagocytic process of phagocytes. In the present
      study, the effects of Siamese crocodile serum on phagocytic activity of
      macrophages as well as the possible involvement of complement in this process
      were examined. The results showed increases in the phagocytosis of both
      Escherichia coli and to a lesser extent, Staphylococcus aureus upon incubation of
      murine macrophage cell line with fresh crocodile serum (FS). Similar to FS, other
      crocodile blood products, including freeze dried serum (DS) and freeze dried
      whole blood (DWB) exhibited phagocytosis-enhancing property. However the ability
      of DWB to enhance phagocytosis was less efficient than that of FS and DS,
      suggesting that serum factors were involved in this process. Treatment of FS with
      heat at 56 degrees C for 30 min deteriorated the effect of FS on bacterial uptake
      of macrophages, suggesting that complement proteins play a role in the modulation
      of the phagocytic process. Collectively, the results of the present study
      suggested that crocodile serum enhances the macrophage phagocytic activity
      through complement activity and, therefore, may be taken as an alternative
      medicine for supporting the human immune responses.

PMID- 22619920
TI  - Inter-rater and intra-rater reliability of the gross motor function measure (GMFM
      66) by Thai pediatric physical therapists.
AB  - OBJECTIVE: The present study aimed to determine inter-rater reliability and intra
      rater reliability of the 66-item version of the Gross Motor Function Measure
      (GMFM-66) in assessing motor ability of Thai children with cerebral palsy.
      MATERIAL AND METHOD: Ten children, aged 2-10 years, were recruited in the present
      study. Eight children with spastic diplegia from an outpatient department of
      Thammasat University Hospital, and two normal children were recruited. The motor
      abilities of the subjects were recorded on a video camera. Three pediatric
      physical therapists independently watched the video recordings and scored each
      child according to the GMFM assessment. The video clips often children were
      assessed on two occasions at an interval of one week by the same therapists. The
      inter-rater and intra-rater reliability were analyzed using an intraclass
      correlation coefficient (ICC). RESULTS: The inter-rater reliability and intra
      rater reliability of the GMFM-66 were both high. The ICC for inter-rater
      reliability was 0.93 and for intra-rater reliability were 0.99-1.00 for the total
      scores. CONCLUSION: The present study confirms high inter-rater and intra-rater
      reliability of the GMFM-66 measured by Thai pediatric physical therapists.
      Therefore, in clinical practice, we recommend Thai pediatric physical therapists
      to use the GMFM-66 in assessing motor ability of cerebral palsy patients.

PMID- 22619921
TI  - Disability and late-life depression: a prospective population-based study.
AB  - BACKGROUND: Previous researches in developed countries have established
      depression as a risk factor for disability in the elderly, but little has focused
      on disability as a contributor to depression. OBJECTIVE: The present study aims:
      1) to describe the 3-month incidences of depression among Thai elders with and
      without disability and 2) to investigate the prospective relationship between the
      disability and depression. MATERIAL AND METHOD: A 3-month prospective population
      based cohort study of 358 elders (142 severe, 89 moderate 127 mild or non
      disabled people), aged 60 years and older and living in rural and urban
      communities, was conducted. Depression was assessed by Euro-D Thai version at
      baseline and 3 months follow-up. Disability was assessed by World Health
      Organization Disability Assessment Schedule (WHODAS-II). Impairment was assessed
      by a modified version of the Burvill Physical Illness Scale. Logistic regression
      modeling was used to determine whether impairment and disability were
      independently associated with the onset of late-life depression. RESULTS: The 3
      month incidences were 5%, 14.29% and 22.61% among the elders with no/mild,
      moderate and severe disability respectively. Both severe disability and a high
      number of impairments were each significantly associated with risk of depression
      (RR3.25 95% CI 1.29-8.18 and RR2.33 95% CI 1.15-4.73, respectively),
      independently of age, gender and socioeconomic status. CONCLUSION: Disability is
      one of the main contributors in depression in late-life. Improving community and
      public facilities and accessing to health services (e.g., medical rehabilitation)
      for disabled older people may not only help to enhance their quality of life but
      also help to prevent depression.

PMID- 22619922
TI  - Antibacterial activity of crude extracts of prasaprohyai formula and its
      components against pathogenic bacteria.
AB  - BACKGROUND: Prasaprohyai formula is a Thai Traditional Medicine which has been
      used for reducing feverish in child. Fever is a symptom resulting from various
      infections and diseases. The major cause of fever is bacterial and viral
      infections. The Prasaprohyai formula and its components potentially have
      biological activities including antipyretic and antimicrobial activities. It is
      in a hope to develop the formula and its components for an alternative medicine
      of infectious diseases. OBJECTIVE: To study antibacterial activity of
      Prasaprohyai formula and its components against pathogenic bacteria. MATERIAL AND
      METHOD: Prasaprohyai formula and its components were extracted by different
      methods, A: maceration with 95% ethanol followed by evaporation (ET), B: ET
      followed by freeze drying (EF) and C: water distillation (VO). All extracts were
      tested against clinical isolates from Thammasat University Hospital,
      Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922. Disk diffusion
      and broth dilution methods were performed. RESULTS: Crude extracts of ET had
      higher yield of extraction than other methods. The results showed that the crude
      extract from different methods of Syzygium aromaticum (Linn) Merr & Perry
      (Flower) was effective against all bacterial strains with the inhibition zone
      ranging from 9 to 19 mm. The VO extract of Prasaprohyai formula showed
      antibacterial activity against most of the pathogenic bacteria in the present
      study. The activity against Streptococcus pyogenes was found in the VO extract of
      some components. The ET extracts of Lepidium sativum Linn, Myristica fragrans
      Houtt (seed) and Myristica fragrans Houtt (aril) had no antibacterial activity
      against all microorganism. However the EF extracts of this formula and some
      components were able to mostly inhibit Gram positive bacteria. CONCLUSION: The
      results indicated that Prasaprohyai formula and its components were able to
      inhibit the growth of both Gram positive and Gram negative bacteria including
      multiresistant strains. The volatile oil extracts seemed to play an important
      role in antimicrobial activities. The development of Prasaprohyai formula for
      alternative medicine will be approached in future.

PMID- 22619923
TI  - Bacterial contamination assay of Thai herbal products.
AB  - BACKGROUND: Herbal products have been globally used for health promotion. These
      products were frequently contaminated with various microorganisms due to raw
      materials and unhygienic production process. Microbiological quality of several
      forms is necessary to determine by microbial contamination assay in order to
      assure the safety of Thai herbal products. OBJECTIVE: To investigate the
      microbiological quality of Thai herbal products commercially distributed from
      different regions of Thailand and marketed in Bangkok and Pathumthani province by
      bacterial contamination assay. MATERIAL AND METHOD: Thai herbal products were
      randomly collected in Bangkok and Pathum Thani province. Total of 94 samples were
      in different dosage forms including liquids, pills, capsules and powders. The
      samples were divided into two groups as Standard Certified and Non-Certified
      herbal products. The products were tested as plate count method using spread
      plate technique. The obtained results were interpreted based on Thai Herbal
      Pharmacopoeia. RESULTS: The total plate counts of Standard Certified samples were
      ranged between less than 30 to 5.8 x 10(7) cfu/g or ml and the Non-Certified
      samples were ranged between less than 30 and 6.0 x 10(6) cfu/g or ml. In
      addition, the results showed that 7 out of 49 (14.28%) of Standard Certified
      sample group and 5 out of 45 (11.11%) of the Non-Certified sample group were out
      of the range of acceptable standard. The finding indicated that the
      microbiological quality of both Standard Certified and Non-Certified Thai herbal
      products showed no significant differences. CONCLUSION: Majority of the herbal
      products tested for bacterial contamination were in acceptable standard. However
      some products were out of acceptable range. Hence the rigorous assessment of
      quality control and good manufactury practice of Thai herbal production is
      necessary for safe consumption.

PMID- 22619924
TI  - Antibacterial activity of extracts from five medicinal plants and their formula
      against bacteria that cause chronic wound infection.
AB  - BACKGROUND: Chronic wound is caused by various factors such as chemotherapy, gene
      damage, treatment with steroids, diabetes mellitus, renal failure, blood
      pressure, infection and nutritional factors. One of the most common causes is
      bacterial infection. Antibacterial activity of several herbal plants has been
      reported. Thai medicinal plants which possess biological activities are potential
      to develop an alternative treatment of bacterial infection. OBJECTIVE: To study
      efficiency of extracts from medicinal plants and their formula against bacteria
      that cause chronic wound infection. MATERIAL AND METHOD: Extraction of Thai
      medicinal plants including Curcuma longa Linn, Rhinacanthus nasutus Linn,
      Garcinia mangostana Linn, Caesalpinia sappan Linn and Centellia asiatica Linn was
      performed by maceration with 95% ethanol and decoction followed by freeze dry.
      Formulation was conducted by varying the ratio of each components. Antibacterial
      activity were determined disk diffusion and broth dilution against Staphylococcus
      aureus, Methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas
      aeruginosa, Acinetobacter baumanii, Escherichia coli and Klebsiella pneumoniae.
      RESULTS: Ethanolic extracts exhibited better antibacterial activity against
      tested strains than water extracts. Antibacterial activity of Caesalpinia sappan
      Linn. against S. aureus and MRSA showed the most effective with MIC value of
      0.625 mg/ml. One of the five different formulas which contained two times
      proportion of C. sappan revealed that this formula was able to inhibit all tested
      strains with the MIC ranging between 0.156 mg/ml and 10 mg/ml. CONCLUSION: C.
      sappan is the most effective herbal plant. The formula with two times proportion
      of C. sappan is potentially best formula for development of medicinal product of
      chronic wound infection. The potential active compound of C. sappan is suggested
      for further investigation of antimicrobial activity and other biological
      properties.

PMID- 22619925
TI  - Antimicrobial activity of the extracts from Benchalokawichian remedy and its
      components.
AB  - BACKGROUND: Infectious diseases cause serious health problems worldwide due to
      multiresistant bacterial strains. Thai traditional formula such as
      Benchalokawichian remedy has been used to relieve fever, common cold and
      influenza. The remedy has been scientifically proved for antipyretic and
      antiseptic activities. However; the remedy and its components have not been fully
      studied for antimicrobial activity against pathogenic bacteria. OBJECTIVE: To
      determine antimicrobial activity of extracts from Benchalokawichian remedy and
      its components against clinical isolates by disk diffusion method. MATERIAL AND
      METHOD: The bacterial strains used in the present study were clinical isolates
      from Thammasat Hospital, Thailand. The ethanolic and water extracts of
      Benchalokawichian remedy and its components were screened for antimicrobial
      activity. The tests were performed in triplicate. The results were recorded by
      measuring diameter of growth inhibition zone. Means +/- SD of the obtained
      results were calculated. RESULTS: The results of antimicrobial activity
      demonstrated that the ethanolic extracts of Benchalokawichian remedy and its
      components were effective against Candida albicans, Gram positive and Gram
      negative bacteria except some isolates. Tiliacora triandra and Clerodendrum
      petasites exhibited the most effective antimicrobial activity among other
      ethanolic extracts. The water extracts of Capparis micracantha, Tiliacora
      triandra and Harrisonia perforata were able to inhibit the tested strains. Both
      etahnolic and water extracts of Tiliacora triandra were the only one component of
      Benchalokawichian remedy that could inhibit the growth of C. albicans.
      CONCLUSION: The present study provides basic knowledge of the antimicrobial
      activity of Benchalokawichian remedy and its components. Tiliacora triandra and
      Clerodendrum petasites were the most effective antimicrobial activity among other
      ethanolic extracts. They are potential candidates to produce medicinal formula
      for alternative medicine. Further study on minimum inhibitory concentration and
      minimum bactericidal concentration assay will be carried out in order to obtain
      more detailed insightful knowledge to develop medicinal products for treatment of
      bacterial infection and other infectious diseases.

PMID- 22619926
TI  - Free radical scavenging and lipid peroxidation of Thai medicinal plants used for
      diabetic treatment.
AB  - OBJECTIVE: To investigate antioxidant activities of some selected plants used to
      treat diabetic patients by Thai folk doctors. MATERIAL AND METHOD: Ten Thai
      plants were selected, macerated and extracted with 95% ethanol. DPPH scavenging
      and lipid peroxidation assays were used to test the antioxidant activities of the
      extracts. RESULTS: Mammea siamensis (Saaraphee), Tacca chantrieri (Narapusri) and
      Albizia myriophylla (Cha Em Thai) showed the highest antioxidant activity on DPPH
      radical assay (EC50 = 10.17, 10.24 and 14.45 microg/ml, respectively). Mimussops
      elengi (Pikun), M. siamensis (Saaraphee) and A. myriophylla (Cha Em Thai)
      exhibited the highest antioxidant activity by lipid peroxidation assay (IC50
      0.39, 0.43 and 0.70 microg/ml, respectively). Six often plant extracts showed
      antioxidant activity on both assays (IC50 < 20 microg/ml). CONCLUSION: These
      plant extracts containing in Thai folklore antidiabetic medicine, which showed
      high antioxidant activity, may be used effectively for the treatment of diabetic
      patients.

PMID- 22619927
TI  - Acetylcholinesterase inhibitory activity of Thai traditional nootropic remedy and
      its herbal ingredients.
AB  - The incidence of Alzheimer disease (AD) is increasing every year in accordance
      with the increasing of elderly population and could pose significant health
      problems in the future. The use of medicinal plants as an alternative prevention
      or even for a possible treatment of the AD is, therefore, becoming an interesting
      research issue. Acetylcholinesterase (AChE) inhibitors are well-known drugs
      commonly used in the treatment of AD. The aim of the present study was to screen
      for AChE inhibitory activity of the Thai traditional nootropic recipe and its
      herbal ingredients. The results showed that ethanolic extracts of four out of
      twenty-five herbs i.e. Stephania pierrei Diels. Kaempfera parviflora Wall. ex
      Baker, Stephania venosa (Blume) Spreng, Piper nigrum L at 0.1 mg/mL showed % AChE
      inhibition of 89, 64, 59, 50; the IC50 were 6, 21, 29, 30 microg/mL respectively.
      The other herbs as well as combination of the whole recipe had no synergistic
      inhibitory effect on AChE activity. However some plants revealed antioxidant
      activity. More research should have be performed on this local wisdom remedy to
      verify the uses in scientific term.

PMID- 22619928
TI  - Initial experience of therapeutic hypothermia after cardiac arrest with surface
      cooling method in Thammasat Chalerm Prakiat Hospital: two cases report.
AB  - OBJECTIVE: Therapeutic hypothermia is a recommended treatment by standard
      guidelines for patients after cardiac arrest but it is not distinguished in
      Thailand. The present report aimed to demonstrate feasibility of its use in
      Thailand. CASE REPORT: Two cases of patients after cardiac arrest treated with
      therapeutic hypothermia are reported. Surface cooling method with Arctic Sun
      system was applied in both cases. Core temperature curve and serial laboratory
      parameters are also reported. CONCLUSION: This initial experience of therapeutic
      hypothermia after cardiac arrest with surface cooling method implicates
      feasibility of its use in Thailand.

PMID- 22619929
TI  - Symptomatic leptomeningeal and entirely intramedullary spinal cord metastasis
      from supratentorial glioblastoma: a case report.
AB  - BACKGROUND: Leptomeningeal with intramedullary spinal cord metastasis rarely
      occur. Most patients have dramatically poor prognosis. The causes of metastasis
      remain unclear and there is still no principle management for this aggressive
      tumor. CASE REPORT: The presentation report demonstrates the clinical features,
      the radiographic study and the histological characteristics in a 46-year-old
      woman who underwent surgical removal of a supratentorial glioblastoma and
      developed symptomatic spinal metastasis. The pathological report confirmed the
      diagnosis by laminectomy and intramedullary tumor biopsy. The analysis of the
      possible factors of metastasis and the management of this circumstance are
      discussed. CONCLUSION: Spinal cord metastasis of Glioblastoma is one of the most
      poor prognostic factors. The most important precipitating factor is the location
      of the tumor which is located near the cerebrospinal fluid cistern. Magnetic
      resonance imaging of the whole spine should be considered in this group of
      patients.

PMID- 22619930
TI  - Subacute sclerosing panencephalitis in immunized Thai children.
AB  - Subacute sclerosing panencephalitis (SSPE) is a progressive neurodegenerative
      disease with high mortality and poor prognosis. This is caused by persistent
      defective measles virus infection. Clinical presentations are variable including
      behavioral-cognitive change, myoclonic seizure, visual problem, spasticity or
      abnormal movement. The authors report a case of 10 year-old boy, previously
      healthy with complete immunization, presenting with frequent myoclonic jerks,
      abnormal movements, spasticity and altered mental status. Electroencephalographic
      (EEG), magnetic resonance imaging (MRI), and laboratory findings are typical for
      SSPE.

PMID- 22619931
TI  - Transient hyperkalemic distal renal tubular acidosis with bicarbonate wasting in
      a young child.
AB  - Distal renal tubular acidosis is a clinical syndrome characterized by inability
      to acidify urine in the presence of metabolic acidosis. Classic dRTA patients
      exhibit failure to thrive, polyuria, metabolic acidosis and hypokalemia.
      Hyperkalemic dRTA without underlying disease is very rare. Transient bicarbonate
      wasting accompanied with hypokalemic dRTA was reported in infants. Herein, a
      transient hyperkalemic dRTA with bicarbonate wasting was reported in a young
      child.

PMID- 22619932
TI  - Failed conservative treatment of synchronous primary cancer of endometrium and
      ovary in a young Thai woman: a case report.
AB  - A case of well differentiated endometriod adenocarcinoma of the endometrium with
      a synchronous endometriod and clear cell adenocarcinoma of both ovaries was
      reported. Recently, a 28-year-old woman presented with vaginal bleeding was
      diagnosed to have only FIGO stage IaG1 (FIGO 2000) cancer of the endometrium.
      After 3 months of high dose progestin treatment, 15 cm bilateral ovarian tumors
      later diagnosed as FIGO stage IIIa ovarian cancer (mixed endometriod and clear
      cell adenocarcinoma) were detected, and later surgically removed. The patient
      then was started on Placitaxel/Carboplatin combination chemotherapy for 6 cycles
      after surgery. The synchronous cancers of endometrium and ovary are usually
      presented in woman with median age of 50 with obesity, diabetes, and
      hypertension. These low grade tumors and better prognosis are the norm in
      contrast to the authors' case with clear cell component and higher stage of
      ovarian cancer in young lean Thai woman.

PMID- 22619933
TI  - Unusual subtrochanteric femoral insufficiency fractures associated with the
      prolonged use of alendronate and risedronate: a report of two cases.
AB  - OBJECTIVE: Previous studies reported that prolonged alendronate use was related
      to insufficiency fractures. Fewer reports presented this phenomenon in patients
      with risedronate use. The present study reported on two patients, both of whom
      had long-term use of alendronate and risedronate then sustained subtrochanteric
      femoral insufficiency fractures with minimal trauma. CASE SUMMARY: One of the
      patients was treated with alendronate therapy in concern of her risk factors for
      osteoporosis (her previous a hysterectomy with bilateral oophorectomy) with
      unsubstantiated evidence of her pretreatment, bone-mineral-density measurements
      (BMD), for a 10-year prior episode of left prodromal thigh pain and an
      insufficiency fracture at 8 days post experiencing the pain. The other patient
      had a history of the hysterectomy and right salpingo-oophorectomy, a low-energy
      metatarsal fracture with resulting osteopenia verified with BMD measurements. She
      was treated with alendronate for 42 months before switching to risedronate for 6
      months per patient's request but no history of prodromal thigh pain.
      Subsequently, she sustained an insufficiency fracture, while standing and turning
      her body. Both patients had the significant long-term uses of bisphosphonate and
      exhibited the typical radiographic characteristics of insufficiency fracture.
      From the present report, risedronate is another prospective medication that might
      be related to insufficiency fractures. CONCLUSION: The present study concluded
      that cautious consideration is essential for long-term alendronate and
      risedronate use for any individual patient. The index of suspicion for the
      subtrochanteric femoral insufficiency fracture should be higher in the patients
      presenting with prodromal thigh pain. Further studies are necessary to identify
      the class effect of other bisphosphonate drugs, the definitive mechanisms between
      all generations of bisphosphonate treatments and their complications, including
      the individual risk factors of the insufficiency fracture.

PMID- 22619934
TI  - [Impact of heavy-duty diesel vehicles on air quality and control of their
      emissions].
AB  - Through an analysis of the characteristics of diesel vehicle emissions and motor
      vehicle emissions inventories, this paper examines the impact of heavy-duty
      diesel vehicles on air quality in China as well as issues related to the control
      of their emissions. Heavy-duty diesel vehicles emit large amounts of nitrogen
      oxides and particulate matter. Nitrogen oxides is one of the important precursors
      for the formation of secondary particles and ozone in the atmosphere, causing
      regional haze. Diesel particulate matter is a major toxic air pollutant with
      adverse effect on human health, and in particular, the ultrafine particles in 30
      100 nm size range can pose great health risks because of its extremely small
      sizes. Motor vehicles have become a major source of air pollution in many
      metropolitan areas and city cluster in China, and among them the heavy-duty
      diesel vehicles are a dominant contributor of nitrogen oxides and particulate
      matter emissions. Hence, controlling heavy-duty diesel vehicle emissions should
      be a key component of an effective air quality management plan, and a number of
      issues related to heavy-duty diesel vehicle emissions need to be addressed.

PMID- 22619936
TI  - [Source and air-sea fluxes of heavy metals in the atmospheric particles of East
      China Sea].
AB  - From 2006 to 2007, four surveys for marine atmosphere in East China Sea were
      carried out included different seasons (spring, summer, autumn and winter). Based
      on the survey data of heavy metals in marine atmospheric particles, analyzed the
      source of heavy metals by the calculation of Enrichment Factors, calculated the
      air-sea fluxes via dry deposition. The results showed, comparing with the crustal
      and seawater, the heavy metals including Cu, Pb, Cd and Zn were highly
      concentrated, mainly from the pollutants of human activities. The fluxes of heavy
      metals via dry deposition were Zn [10.92 mg/(m2 x a)] > Pb [2.299 mg/(m2 x a)] >
      Cu [1.611 mg/(m2 x a)] > Cd [0.017 mg/(m2 x a)]. The fluxes of heavy metals in
      winter were highest,the summer and autumn were lower. The input of Cu, Pb, Zn and
      Cd from atmosphere to sea via dry deposition was 2 376 t, nearly 13% compared
      with the input of The Changjiang River (Yangtze River).

PMID- 22619935
TI  - [Review of the factors influencing the temporal and spatial variability of soil
      respiration in terrestrial ecosystem].
AB  - Soil respiration is an important process in carbon cycling. Understanding the
      processes and controlling factors of soil respiration are crucial in
      investigating the terrestrial carbon cycling. This article reviews the
      investigations about the factors controlling the temporal and spatial variability
      of soil respiration. The temporal and spatial variability in soil respiration is
      linked with climate, vegetation and soil factors. Air temperature and
      precipitation generally contribute great to the variability of soil respiration.
      Leaf area index (LAI), litter fall and fine root biomass are three plant-related
      factors that can be employed to explained the variability of soil respiration,
      while soil carbon content and texture are two soil factors responsible for the
      variability of soil respiration. Generally, climate, vegetation and soil factors
      contribute collectively to the temporal and spatial variability of terrestrial
      soil respiration. Temperature and precipitation, on the one hand, directly affect
      the root and microbial respiration rates. On the other hand, temperature and
      precipitation indirectly affect soil respiration by influencing the plant and
      microbial growth and soil conditions. In order to understand the controlling
      factors of the temporal and spatial variability of soil respiration, there are
      four main issues need to be addressed. The issues include quantitatively
      partitioning the autotrophic and heterotrophic components of soil respiration,
      standardizing the method and scale of measuring soil respiration, coupling
      measurements of soil respiration with environmental factors and performing more
      measurements of soil respiration in wetland ecosystems.

PMID- 22619937
TI  - [Composition and source of atmosphere aerosol water soluble ions over the East
      China Sea in winter].
AB  - With the ion chromatographic method, the water-soluble ion concentrations of Cl(
      ), NO3(-), SO4(2-) , CH3SO3(-) (MSA), Na+, K+, NH4+, Mg2+ and Ca2+ in the
      atmospheric aerosol over the East China Sea in winter 2009 was determined and the
      sources of these ions was investigated through correlation analysis by SPSS
      (statistical package for social sciences) software. The results indicated that
      the concentrations of secondary ions in aerosol were the highest (non-sea-salt
      sulfates nss-SO4(2-), NO3(-), NH4+), accounting for 78.4% of total determining
      ions. The calculation results of equivalent concentration of anions and cations
      showed that the acid ions of aerosol were neutralized inadequately. The
      stoichiometry of NH4+ in different compounds showed that NH4HSO4 was the main
      binding form of NH4+ and SO4(2-) in the aerosol. The concentration of
      methanesulfonic acid (MSA) was low, and the average value was (0.0088 +/- 0.0037)
      microg x m(-3). According to calculation, the contribution of sea-salt sulfates
      was 4.5% to total sulfates, and that of biogenous sulfates was 1.4% to non-sea
      salt sulfate (nss-SO4(2-)), showing that human input was the main source of
      sulfates in aerosol over the East China Sea. In addition, nss-SO4(2-)/NO3(-) in
      the aerosol was 1.08, reflecting that China's energy structure adjustment played
      an important role in recent years.

PMID- 22619938
TI  - [Distribution, flux and photoproduction of carbon monoxide in the Yellow Sea and
      the Bohai Sea in spring].
AB  - Concentration distribution, sea-to-air flux, photoproduction of carbon monoxide
      (CO) in the surface seawater and atmospheric CO mixing ratio were measured in the
      Yellow Sea and the Bohai Sea. A headspace analysis system was used for CO
      measurement. The concentrations of CO in the surface seawater ranged from 0.19 to
      3.57 nmol x L(-1), with an average of 1.24 nmol x L(-1) ( SD = 0.79, n = 69).
      Overall, the concentrations of CO displayed a decreasing trend from the coast to
      the offshore stations and followed diurnal variations after classifying and
      averaging the CO concentrations according to sampling and analysing time in the
      unit of one hour, with the maximum values in midnoon which was 10 folds higher
      than the minimum values in predawn. Atmospheric CO mixing ratios varied from 215
      x 10(-9) to 850 x 10(-9), with an average of 414 x 10(-9) (SD = 140 x 10(-9), n =
      69), due to obvious terrestrial input. The supersaturation factors of CO varied
      from 0.42-18.90, with an average of 3.61 (SD = 2.99, n = 69), indicating that the
      Yellow Sea and the Bohai Sea was a net source of atmospheric CO. The average sea
      to-air fluxes of CO from the Yellow Sea and the Bohai Sea were estimated to be
      (1.22 +/- 1.70) micromol x (m2 x d)(-1) by the LM86 equation and (2.13 +/- 2.91)
      micromol x (m2 x d)(-1) by the W92 equation, respectively. Using SMARTS2 spectral
      irradiance model to estimate CO production, the photoproduction rate of CO was
      54.60 micromol x (m2 x d)(-1) and the photoproduction of carbon in the Yellow Sea
      and the Bohai Sea was 26.95 x 10(9) g in spring. The photoproduction rate of CO
      was 25-50 times higher than the sea-to-air flux, suggesting that most part of CO
      was removed by microbial process in the surface seawater.

PMID- 22619939
TI  - [Estimating spatiotemporal dynamics of methane emissions from livestock in
      China].
AB  - Combining Tier 2 method presented in the guidelines of the Intergovernmental
      Panel on Climate Change (IPCC, 2006) with GIS techniques, a primary estimation of
      methane emission from livestock in 2004 (including emission from enteric
      fermentation and manure management system) was made with county-level livestock
      statistics and 1 km x 1 km raster data. The results indicated that the methane
      emission from livestock was 12.79 x 10(6) tons totally in China, and 11.64 x
      10(6) tons from enteric fermentation and 1.16 x 10(6) tons from manure
      management. The uncertainties of the methane emission from enteric fermentation
      and manure management were +/- 35.10% and +/- 14. 58% respectively. The high
      methane emission was at Yellow River basin, especially in the lower reaches of
      the Yellow River and the North China Plain. The Southwestern China also can be
      found with high emission. In accordance with the seasonal temperature changes,
      the temporal variation of manure management emission was estimated the highest in
      summer and the lowest in winter.

PMID- 22619940
TI  - [Characteristics of atmospheric CO2 concentration and variation of carbon source
      & sink at Lin'an regional background station].
AB  - Characteristics of Atmospheric CO2 concentration obtained by Flask measurements
      were analyzed at Lin'an regional background station from August 2006 to July
      2009. According to the simulation results of carbon tracking model, the impact of
      carbon sources and sinks on CO2 concentration was evaluated in Yangtze River
      Delta. The results revealed that atmospheric CO2 concentrations at Lin'an
      regional background station were between 368.3 x 10(-6) and 414.8 x 10(-6). The
      CO2 concentration varied as seasons change, with maximum in winter and minimum in
      summer; the annual difference was about 20.5 x 10(-6). The long-term trend of CO2
      concentration showed rapid growth year by year; the average growth rate was about
      3.2 x 10(-6)/a. CO2 flux of Yangtze River Delta was mainly contributed by fossil
      fuel burning, terrestrial biosphere exchange and ocean exchange, while the
      contribution of fire emission was small. CO2 flux from fossil fuel burning played
      an important role in carbon source; terrestrial biosphere and ocean were
      important carbon sinks in this area. Seasonal variations of CO2 concentration at
      Lin'an regional background station were consistent with CO2 fluxes from fossil
      fuel burning and terrestrial biosphere exchange.

PMID- 22619941
TI  - [Pollution characterization and source apportionment of polybrominated diphenyl
      ethers in autumn air of Xi'an].
AB  - Air samples in gas and particle phases were collected using a high volume active
      sampler from August to October in 2008 at Xi'an for evaluating the pollution
      level of polybrominated diphenyl ethers (PBDEs). Lower brominated PBDEs and BDE
      209 were analyzed via GC-MS and GC/ECD, respectively. The total concentrations
      (gas plus particle phases) of 12 PBDEs were ranged from 37.43 to 620.30 pg/m3,
      with an average of 216.28 pg/m3, while tri- to hexa-brominated congeners (Sigma11
      PBDEs) ranged from 16.32 to 86. 49 pg/m3, BDE-209 ranged from 16. 34 to 576.01
      pg/m3. Tri- to tetra-brominated congeners existed mainly in gas phase, tetra- to
      hexa-brominated congeners were predominated in particle phase, and BDE-209 was
      detected only in particle phase. The proportion of PBDEs in particle phase
      increased with bromine number. Gas-particle partition coefficient of PBDEs was
      well correlated with sub-cooled liquid vapor pressure, and the partitioning of
      PBDEs between gas and particle phases were close to equilibrium. Correlation
      analysis indicated that all the PBDEs have good coefficients except BDE-85.
      Source analysis indicated that PBDEs in the atmosphere of Xi'an were mainly from
      the Penta-BDE and Deca-BDE contamination.

PMID- 22619942
TI  - [Application of artificial neural networks on the prediction of surface ozone
      concentrations].
AB  - Ozone is an important secondary air pollutant in the lower atmosphere. In order
      to predict the hourly maximum ozone one day in advance based on the
      meteorological variables for the Wanqingsha site in Guangzhou, Guangdong
      province, a neural network model (Multi-Layer Perceptron) and a multiple linear
      regression model were used and compared. Model inputs are meteorological
      parameters (wind speed, wind direction, air temperature, relative humidity,
      barometric pressure and solar radiation) of the next day and hourly maximum ozone
      concentration of the previous day. The OBS (optimal brain surgeon) was adopted to
      prune the neutral work, to reduce its complexity and to improve its
      generalization ability. We find that the pruned neural network has the capacity
      to predict the peak ozone, with an agreement index of 92.3%, the root mean square
      error of 0.0428 mg/m3, the R-square of 0.737 and the success index of threshold
      exceedance 77.0% (the threshold O3 mixing ratio of 0.20 mg/m3). When the neural
      classifier was added to the neural network model, the success index of threshold
      exceedance increased to 83.6%. Through comparison of the performance indices
      between the multiple linear regression model and the neural network model, we
      conclud that that neural network is a better choice to predict peak ozone from
      meteorological forecast, which may be applied to practical prediction of ozone
      concentration.

PMID- 22619943
TI  - [Influence of exogenous sulfur-containing compounds on the exchange fluxes of
      volatile organic sulfur compounds].
AB  - The influences of cysteine, sodium sulfide (Na2S) and sodium sulfate (Na2SO4) on
      the soil-air exchange fluxes of volatile organic sulfur compounds (VOSCs),
      including carbonyl sulfide (COS), dimethyl sulfide (DMS), carbon disulfide (CS2)
      and dimethyl disulfide (DMDS), were studied employing static chamber enclosure
      followed by laboratory determination using an Entech 7100 preconcentrator coupled
      with an Agilent 5973 GC-MSD. The results showed that after the addition of
      cysteine, the soil for the exchange fluxes of COS and CS2 shifted to be the
      source from sink and the emissions of DMS and DMDS increased significant. The
      emission amount of DMS and CS2 accounted for 89.2% to the total VOSCs after the
      addition of cysteine, implying that cysteine is an important precursor for DMS
      and CS2 in the soil. The amount of DMDS accounted for 93.2% to the total sulfur
      from the soil after addition of Na2S, indicating that Na2S is a key precursor for
      DMDS. No significant difference of VOSCs fluxes was found between the controlled
      soil and the soil with addition of Na2SO4, suggesting Na2SO4 was not the direct
      precursor for VOSCs in soil. VOSCs exchange rates reached the maximum at 6 to 8
      days after addition of cysteine. As for addition of Na2S, the maximal emission
      rates of different VOSCs appeared at different dates, and the dates differed
      significantly from those after addition of cysteine, implying that the formation
      process of VOSCs from the soil with addition of Na2S was more complex and
      different from the soil with addition of cysteine.

PMID- 22619944
TI  - [Research on SCR denitrification of MnOx/Al2O3 modified by CeO2 and its mechanism
      at low temperature].
AB  - The Al2O3,which has large specific surface area and is used as carrier,was
      prepared by sol-gel method in this study. Series catalysts of MnOx, CeO2 plus
      MnOx supported on Al2O3 by isometric impregnation method. The SCR denitrification
      experimental conditions were as follows: NH3 as reductive agent, certain gas
      velocity and suitable ratio of gas mixed was setup. Furthermore, the experiments
      of BET, XRD and SEM were also carried out respectively in order to obtain
      physicochemical properties of the prepared catalysts. The experimental results
      showed that the loading of active component and calcination temperature made a
      big difference to the catalysts' performance. With appropriate addition of CeO2,
      MnOx/Al2O3 exhibits better activity and stability. For MnOx/Al2O3, the catalytic
      activity on NO was greatly influenced by its loaded content, and 7% MnOx/Al2O3
      showed superior catalytic activity among the MnOx/Al2O3. The addition of CeO2
      could greatly improve the dispersibility of MnOx on the carrier and increase its
      catalytic activity. The 4% CeO2 addition was the optimum loaded mass precent.
      Forthermore, 550 degrees C is the best calcination temperature, as MnOx formed
      different crystalline phases with temperature, at the same time, the addition of
      CeO2 could affect MnOx crystalline phase. The catalytic mechanism of SCR on NO
      was also discussed.

PMID- 22619945
TI  - [Development characteristics of aquatic plants in a constructed wetland for
      treating urban drinking water source at its initial operation stage].
AB  - The development characteristics and improvement measures of aquatic plants were
      studied in Shijiuyang Constructed Wetland (SCW) at its initial operation stage.
      SCW was a large-scale wetland aiming to help relieve the source water pollution
      in Jiaxing City. A checklist of vascular plants in SCW was built, and species
      composition, life forms, biomass and association distributions were examined. Our
      objectives were to examine the diversity and community structure of aquatic
      plants in SCW at its initial operation stage, and to find out the possible
      hydrophyte improvement measures. The survey results showed that there were 49
      vascular plant species belonging to 41 genera, 25 families in SCW, which greatly
      exceeded the artificially transplanted 13 species. The life forms of present
      aquatic plants in SCW were dominated by hygrophilous plants (20 species) and
      emerged plants (17 species), which accounted for 75.5% of the total number of
      aquatic plants. The aquatic plants transplanted artificially were dominated by
      emerged plants (accounted for 69.2%), while those naturally developed were
      predominated by hygrophilous plants (accounted for 47.2%). The horizontal
      distribution of aquatic plant community in SCW was mixed in the form of mosaics,
      which made up typical association complex. Except association Aeschynomene indica
      L., the dominant species of other associations were all those transplanted
      artificially. The naturally grown species scattered throughout the SCW and only
      occupied a small percentage. A marked difference was detected on the species and
      species richness of aquatic plants in different regions of SCW. Biomass of
      aquatic plant associations in SCW was 167.7 t. SCW has shown a trend of
      succession heading for quick increase of plant diversity at the primary operation
      stage. This trend provides a good material base for the future stable community
      of aquatic plants in SCW. According to the current status of aquatic plants, some
      suggestions were put forward on the further optimization and utilization of
      aquatic plant systems in SCW.

PMID- 22619947
TI  - [Effect of inorganic carbon supplement on the growth and lipid accumulation
      properties of Scenedesmus sp. LX1].
AB  - With secondary effluent as growth medium, the growth and lipid accumulation
      properties of Scenedesmus sp. LX1 in the control and carbon supplement (Na2CO3,
      NaHCO3 and CO2) groups were compared. After 14 days of cultivation, there was no
      significant difference in growth and lipid accumulation of Scenedesmus sp. LX1
      among the 4 groups. The algal biomass, lipid and triacylglycerols production were
      0.70-0.77 g x L(-1), 0.27-0.34 g x L(-1) and 0.029-0.033 g x L(-1), respectively,
      and the lipid content per algal biomass was 35% - 45%. The microalgal
      photosynthesis would increase the water's pH to about 9.2, which could induce CO2
      transferring into secondary effluent. In control group, the amount of CO2
      transferring from atmosphere into secondary effluent was 1.0 g x L(-1), occupying
      97% of total fixed CO2 by microalga. Calculation shows that, the CO2 transferring
      from atmosphere into secondary effluent is enough to support microalgal growth
      and lipid accumulation. Therefore, to cultivate Scenedesmus sp. LX1 in secondary
      effluent, there is no need of carbon supplement.

PMID- 22619946
TI  - [Influence of nutrient sources on Anabaena spiroides growth and odorous compounds
      production characteristics].
AB  - The occurrence of taste and odors, produced by secondary metabolites of
      cyanobacteria, has been one of the major water quality problems in drinking
      water. However, the odorous compounds produced by cyanobacteria usually differ
      significantly with different species. One cyanobacterium isolated from Yanghe
      reservoir was identified as Anabaena sp., which can produce high level of geosmin
      consistently during laboratory culture. By culture expanding experiments, the
      algal growth and geosmin production characteristics of the Anabaena sp. were
      studied on different conditions of nitrogen and phosphorus sources. The results
      indicated that geosmin mainly remained in the intracellular algal cells
      regardless of the nutrient sources, and the extracellular content was only in th
      range of 0.2% - 9.6%. Compared with ammonia nitrogen conditions, the growth of
      Anabaena sp. in nitrate nitrogen conditions was much higher, with a 1.4-fold
      variation in geosmin production. While ammonia nitrogen concentration was 0.5
      mg/L, the algal biomass and geosmin production achieved the highest level of 3.8
      x 10(4) cells, mL(-1) and 1.1 x 10(4) ngL(-1), respectively. When the nitrate
      nitrogen concentration was 2.0 mg/L, the algal biomass and geosmin production
      achieved the highest level of 6.6 x 10(4) cells x mL(-1) and 1.3 x 10(4) ng x L(
      1), respectively. Compared with nitrogen sources, the growth of Anabaena sp.
      could be promoted significantly until phosphorus level attained 0.12 mg/L,
      indicating that phosphorus is the main limiting nutrient source for Anabaena sp..
      For Yanghe reservoir, the nutrient level has already been enough for the growth
      of Anabaena sp. Therefore, the nutrient source content, especially phosphorus,
      should be reduced effectively to control the cyanobacterium bloom and taste and
      odor problems.

PMID- 22619948
TI  - [Allelopathy of Hydrodictyon reticulatum on Microcystis aeruginosa and its
      removal capacity on nitrogen and phosphorus].
AB  - The effects of liquid culture after cultured with Hydrodictyon reticulatum on the
      growth of Microcystis aeruginosa were investigated by measuring the D680 value
      and the chlorophyll-a content of M. aeruginosa. The inhibitory effects of H.
      reticulatum on M. aeruginosa were studied in both isolated culture and co-culture
      conditions. Nitrogen and phosphorus removal capacity of H. reticulatum was also
      tested. Results showed that H. reticulatum could inhibit the growth of M.
      aeruginosa obviously. After treated by the liquid culture after cultured with H.
      reticulatum for 8 days, the mortality rate of M. aeruginosa reached 92%. The
      inhibitory effects of H. reticulatum at different concentrations on M. aeruginosa
      were different. The strongest inhibitory effect occurred with 3 g/L H.
      reticulatum in the isolated culture as the D680 value reduced from 0.1 to 0.004
      in 10 days, and it occurred with 4 g/L H. reticulatum in the co-culture as the
      suppression ratio was 96%. Comparing the large-scale death time for cells under
      these two conditions, the inhibitory effects of H. reticulatum in the isolated
      culture were stronger than those in the co-culture. The concentrations of
      nitrogen and phosphorus decreased sharply under both conditions, which showed
      that H. reticulatum had removal capacity on nitrogen and phosphorus. The decrease
      speed of nitrogen and phosphorus concentrations positively correlated to the
      concentrations of H. reticulatum. The highest decrease of nitrogen and phosphorus
      were 93.4 mg/L and 4.58 mg/L in 10 days, respectively.

PMID- 22619949
TI  - [Correlation analysis among characters of gas vesicle in Microcystis strains].
AB  - In order to explore the roles of gvpA copies and repeated sequences of gvpC,
      three Microcystis strains including M. aeruginosa FACHB910, M. aeruginosa
      FACHB930 and M. wesenbergii FACHB929 were used in this research. The length and
      diameter of gas vesicle, relative gas vesicle volume, appear pressure values,
      critical pressure values, cell turgor values were measured, and the correlations
      among these characters, gvpA copies, and repeated sequences of gvpC were
      analyzed. The results indicate that there are a significant positive linear
      correlation between gvpA copies and relative gas vesicle volume (r = 0.999); gvpA
      copies are negatively correlated with diameter of gas vesicle (r = -0.861).
      However, repeated sequences of gvpC have a significant positive correlation with
      diameter of gas vesicle (r = 0.911), and have significant negative correlations
      with relative gas vesicle volume, appear pressure values and critical pressure
      values, with the correlation coefficient of -0.851, - 0.999, - 0.928
      respectively. So we presume that gvpA copies are probably the primary impact
      factor for relative gas vesicle volume. The diameter of gas vesicle is not only
      regulated by repeated sequences of gvpC, but also regulated by gvpA copies.

PMID- 22619950
TI  - [Study on bromate formation of catalytic ozonation process].
AB  - In a batch reactor, the BrO3(-) formation was investigated in the ozonation and
      catalytic ozonation of Br(-)-containing Yellow river water, using the different
      heterogeneous catalysts. The results showed that BrO3(-) minimization was
      achieved in the catalytic ozonation with NiO, CuO, Fe3O4 and Al2O3 as catalysts
      and the percent reductions of BrO3(-) were 34.0%, 32.8%, 29.2% and 20.8%
      respectively. In the reaction R(ct), the ratio of concentration of *OH to O3,
      decreased with the reaction time, and the range of R(ct) was from 10(-8) to 10(
      6). In the ozonation process, one of the main reaction pathways of BrO3(-)
      formation was the combination oxidation of Br(-) by *OH and then O3, another was
      the combination oxidation of Br(-) by O3 and then *OH. In the catalytic ozonation
      with Fe3O4 catalyst, the main pathway was the combination oxidation by *OH and
      then O3. Moreover, about 60.7% removal for UV254 was obtained after 20 min in the
      catalytic ozonation reaction. In our study, it was found that the catalytic
      ozonation process can effectively minimize the formation of BrO3(-) and also
      oxidize organic compounds.

PMID- 22619951
TI  - [Transport of hydroxyapatite nanoparticles in saturated packed column: effects of
      humic acid, pH and ionic strengths].
AB  - Quartz sand was selected as collector and saturated packed column was constructed
      to explore the effects of environmental factors (humic acid, pH and ionic
      strengths of the bulk solution) on the transport and fate of hydroxyapatite
      nanoparticles (Nano-HAP) through measuring zeta potentials and representative
      c(i)/c(0) of Nano-HAP. It was suggested that zeta potentials of Nano-HAP colloids
      became more negative with increasing humic acid concentration and the change in
      solution composition from 0 to 10 mg/L humic acid yielded an increase in the zeta
      potentials of Nano-HAP colloids from -15 mV to -55 mV and a sharp decrease in a
      (attachment efficiency) from 1.0 to 0.012, meanwhile, the increase in bulk
      solution pH yielded a slight decrease in a which enhancing its transportation in
      saturated packed column. However, zeta potentials of Nano-HAP colloids became
      less negative as the ionic strength of bulk solution increased due to the
      compression of diffuse double layer and yielded an increase in a which greatly
      impeded its mobility during the pore-water solution, meanwhile, divalent cations
      have significantly stronger influence on the transport of Nano-HAP than
      monovalent cations of the bulk solution. The increase in the concentration of
      monovalent cation (Na+) from 1 to 100 mmol/L yielded an increase in a from 0.030
      to 0.13, and divalent cations (Ca2+) from 0.2 to 10 mmol/L yielded a greatly
      increase in alpha from 0.030 to 1.0. It is important to note that the results
      could considerably contribute to gain insights in the transport and fate of Nano
      HAP in natured and engineered porous media.

PMID- 22619952
TI  - [Sodium hypochlorite disinfection on effluent of MBR in municipal wastewater
      treatment process].
AB  - Sodium hypochlorite (NaClO) used in wastewater disinfection was assessed by
      examining its performances in lab fed by the effluent from a MBR treatment plant.
      The influence of sodium hypochlorite initial concentrations (0.5-3.0 mg/L) on the
      presence of indicator microorganisms (total coliforms, fecal coliforms),
      disinfection by-products (DBPs) concentrations and the acute toxicity were
      evaluated. Results indicate the total coliforms and the fecal coliform were 1500
      2400 and 10-40 CFU/L, which is difficult to meet the present reclaimed water
      quality standards. A chlorine dose of 2.0 mg/L and contact for 1 h could achieve
      a 3 lg indicator bacteria reduction in MBR effluent samples. THMs
      (trihalomethanes) analysis indicated that concentrations of THMs increase with
      the raise of the active chlorine dose. After adding sodium hypochlorite 1 h the
      concentrations of trihalomethanes (THMs) were 16.22, 7.35 microg/L respectively
      and chloroform (TCM) accounted for 87% of THMs, the haloacetic acids (HAAs) was
      involved trichloroacetic acid (TCAA) 2.01 microg/L, dichloroacetic acid (DCAA)
      1.58 microg/L and under the national limits. Luminescence bacteria acute toxicity
      analysis showed that the chlorinated effluent has higher inhibition rate (48%) in
      comparison to the control with a chlorine dosage of 3.0 mg/L. The results which
      could provide theoretical basis to production show that NaClO disinfection not
      only can inactivate microbe with the DBPs and acute toxicity of the effluent
      under the safety limits, but also meet the requirement of health and safety.

PMID- 22619953
TI  - [Characteristics of Pb2+ and Cd2+ sorption in aqueous solution by wheat straw].
AB  - Wheat straw was used as biosorbent for lead and cadmium removal from aqueous
      solution. Especially, the effect of solution pH, contact time and ions
      concentration on the sorption process was intensively discussed. Result indicated
      that the metal removal was strongly dependent on solution pH and the sorption
      capacity increased with the increasing of solution pH in the pH range of 2.0-6.0.
      The sorption kinetic process fit well with the pseudo-second-order. Langmuir
      isotherm equation was used to evaluate the sorption capacity of the biomass. The
      q(max) values for Pb2+ and Cd2+ were 0.15 mmol x g(-1) and 0.11 mmol x g(-1)
      respectively. After NaOH hydrolated, wheat straw showed higher sorption capacity
      both for Pb2+ and Cd2+, q(max) values for Pb2+ and Cd2+ reached 0.31 and 0.22
      mmol x g(-1) respectively. While the sorption capacity for Pb2+ and Cd2+ on
      esterified wheat straw decreased greatly. Fourier transform infrared spectroscopy
      (FTIR) analysis showed that carboxylic groups on the biomass play an important
      role in Pb2+ and Cd2+ sorption process.

PMID- 22619954
TI  - [Degradation of aniline by a dual-electrode electrochemical oxidation process].
AB  - The efficiency and the mechanism of aniline degradation by an electrochemical
      oxidation process using a Ti/SnO2-Sb2O5 electrode as the anode and a graphite
      electrode as the cathode, were studied in two aqueous electrolytes with/without
      Fe2+. The results showed that the reasonable anodic potential was about 2.0 V +/-
      0.1 V for Ti/SnO2-Sb2O5 electrode to oxidize organic compounds, while the optimum
      cathodic potential was -0.65 V for graphite electrode to reduce O2 generating
      H2O2. The oxidation degradation of aniline could not take place only by the
      single action of H2O2. Anodic oxidation was accounted for the degradation of
      aniline in the absence of Fe2+, while in the presence of Fe2+ both electro-Fenton
      oxidation and anodic oxidation (dual-electrode electrochemical oxidation) could
      degradate aniline effectively, and in this case the former was the main
      mechanism. Under the conditions of -0.65 V cathodic potential, pH 3.0 and 0.5
      mmol x L(-1) Fe2+, the removal rate of COD was 77.5% after 10 h treatment and a
      current efficiency of 97.8% for COD removal could be obtained. This work
      indicates that the dual-electrode electrochemical oxidation is feasible for the
      degradation of organic compounds with a high current efficiency by using Ti/SnO2
      Sb2O5 as anode as well as the reasonable anodic and cathodic potentials.

PMID- 22619955
TI  - [Simultaneously removal of COD, nitrogen and phosphorus from wastewater by
      coupling treatment system with immobilized algae-bacteria].
AB  - A coupling treatment system was developed by employing immobilized Chlamydomonas
      reinhardti and activated sludge to simultaneously remove COD, nitrogen and
      phosphorus from wastewater. The amount of wastewater treated by the system was 6
      m3 per day, and hydraulic retention time was 12 h. For activated sludge section,
      as stirring rate of anaerobic tank was 15 r x min(-1) and DO value of aerobic
      tank was 5 mg x L(-1), COD decreased from about 150 mg x L(-1) to 50 mg x L(-1)
      and NH4+-N from 20-30 mg x L(-1) to 0.5 mg x L(-1), whereas TP only dropped from
      2-3 mg x L(-1) to 1.0 mg x L(-1). For immobilized C. reinhardti section, the
      suitable conditions were: DO 5 mg x L(-1), illumination intensity 2000 lx, the
      loading ratio of immobilization pellets 20%, respectively. Under the appropriate
      conditions of the coupling treatment system, COD, NH4+-N and TP of the effluent
      were about 15 mg x L(-1), 0.5 mg x L(-1) and 0.5 mg x L(-1), respectively. During
      2 months period of continuous treatment, COD, NH4+-N and TP of the effluent kept
      fairly constant, showing the stability of the coupling wastewater treatment
      system.

PMID- 22619956
TI  - [Factors of the rapid startup for nitrosation in sequencing batch reactor].
AB  - The approach and factors for realizing the rapid startup of nitrosation were
      researched at the low level of dissolved oxygen (DO) in sequencing batch reactor
      (SBR). The main parameters of the reactor were controlled as follows: DO were
      0.15-0.40 mg/L, pH values kept from 7.52 to 8.30, temperature maintained at 22.3
      27.1 degrees C, and time of aeration was 8 hours. The purpose of rapid startup
      for nitrosation was achieved after 57 cycles (36 d) with the alternative influent
      of high and low ammonium wastewater (the mean values were 245.28 mg/L and 58.08
      mg/L respectively) in a SBR, and the nitrosation rate was even 100%. Factors of
      accumulation of nitrite were investigated and the effects of DO and pH were
      analyzed during the startup for nitrosation. The results showed that it could
      improve the efficiency of nitrosation when DO concentration was increased
      appropriately. The activity of nitrite oxidizing bacteria (NOB) was recovered
      gradually when DO was higher than 0.72 mg/L. The key factor of controlling
      nitrosation reaction was the concentration of free ammonia (FA), while the final
      factor was the concentration of DO. pH was a desired controlling parameter to
      show the end of nitrification in a SBR cycle, while DO concentration did not
      indicate the finishing of SBR nitrification accurately because it increased
      rapidly before ammonia nitrogen was oxidized absolutely.

PMID- 22619957
TI  - [Performance of new solid carbon source materials for denitrification].
AB  - Organic carbon is needed as the electron donor in the process of reduction of
      nitrate transformation to nitrogen gas, which is essential for biological
      denitrification. Based on previous research, agriculture wastes including
      corncob, rice hull, rice straw and sawdust were selected as potential carbon
      source for denitrification. Using the static organic material of carbon source
      leaching kinetics test and orthogonal experiments of external factors on carbon
      emission process, carbon release and its mechanism of a variety of carbon
      materials were studied. Study showed that release process of various types of
      carbon source materials follows the second dynamics formula, the release curve
      displayed a better double-reciprocal relationship. It revealed that release
      amount of rice straw was the highest and sawdust was the lowest. Results showed
      that corncob could better be used as carbon source for denitrification.
      Orthogonal test indicated that the increasing of solid-liquid ratio and water
      temperature would lead to an enhanced release capacity of carbon, however, the
      change of pH had no significant effect on release capacity of carbon; according
      to significant degree of water temperature, pH, solid-liquid ratio impacted on
      the carbon release, it was sorted by solid-liquid ratio > temperature > pH.

PMID- 22619958
TI  - [Enhanced enzymatic hydrolysis of excess sludge by surfactant].
AB  - In order to enhance the efficiency of enzymatic hydrolysis of excess sludge,
      sodium dodecyl sulfate (SDS) was added to the system to explore the feasibility
      of promotion the enzyme hydrolysis. The results showed that the enzymatic
      hydrolysis of excess sludge could be greatly improved by SDS, and the mixed
      enzymes system was more effective than that by single enzyme system. SCOD
      releasing increased linearly with the increase of SDS dosage at the mixed enzymes
      concentration of 0.06 g/g. SCOD/TCOD increased from 1.3% to 54.3% and VSS
      reduction achieved to 43.2% at the SDS dosage of 0.20 g/g. Further studies
      indicated that SDS could improve the activity of external enzymes. At SDS dosage
      of 0.10 g/g, the protease activity of SDS + protease showed a 2. 3-time increase
      and the amylase activity of SDS + amylase showed a 1.2-time increase compared
      with enzymatic treatment. After 4 h hydrolysis, the concentration of protein,
      NH4+ -N and soluble sugar in SDS + mixed enzymes system were improved by 85.4%,
      92.5% and 64.0%, respectively. Correspondingly, sludge hydrolysis within prior 4
      h was consistent with first-order reaction dynamics. The reaction rate constant
      (K) of soluble sugar increased from 0.23 to 0.41, which indicated that the
      reaction rate of hydrolysis increased significantly.

PMID- 22619959
TI  - [Influence of extracellular polymeric substance on enzyme hydrolysis of sludge
      under anaerobic condition].
AB  - The effect of extracellular polymeric substance (EPS) on the enzymatic
      solubilisation of sludge and the changes of chemical components was investigated.
      Sludge solubilization with and without EPS was studied in the enzymatic system,
      and in the normal system without enzyme addition, respectively. The result
      indicated that only EPS could be hydrolyzed when the enzyme addition less than 20
      mg/g, while the cell lysis occurred significantly with the doses of enzymes
      increasing. Treatment with lysozyme for the original sludge was proved to have a
      higher hydrolysis efficiency, and the SCOD/TCOD rate reached up to 28.14%. And at
      the enzyme dosage of 60 mg/g, the VSS removal rate increased to 51.66% and the
      concentration of DNA attained 68.34 mg/g (calculated by VSS) after 48 h reaction,
      which were 29.01% and 59.63 mg/g higher than the control test, respectively, and
      were 24.86% and 53.39 mg/g higher than that with EPS removed in advance,
      respectively. Meanwhile, NH4+ -N, PO4(3-)-P and SCOD showed high dissolution
      efficiency, and the maximal concentrations achieved to 503 mg/L, 78.9 mg/L and
      3171 mg/L, respectively. After removal of extracellular polymers, higher lysis
      efficiency was also observed by protease and cellulose, by which VSS reduction
      rate reached to 49.95% and 39.85%, respectively. The concentration of DNA showed
      a correlation coefficient of more than 0.9 with the concentrations of SCOD, NH4+ 
      N and PO4(3-)-P. And the highest hydrolysis rate obtained in 6 hours, which was
      about 3 hours earlier than the control test. Moreover, under those condition,
      sludge hydrolyzation could be well realized by only small amount of the enzyme
      addition.

PMID- 22619960
TI  - [Growth kinetics of aquatic worms feeding on activated sludge].
AB  - The growth kinetics of aquatic worms was investigated from juvenile to decline
      phase for 18 weeks by cultivating with activated sludge in batch test. Results
      showed that the growth of aquatic worms well fit Gauss function for cultivating
      18 weeks. The maximum specific growth rate, growth yield of aquatic worms and
      sludge reduction rate was 0.41 d(-1), 0.32 and 25.5%, respectively. When the
      concentration of substrate and dissolved oxygen change from low to high, the
      relationship between the specific growth rate with dissolved oxygen, and
      substrate concentration meet the Monod equation. Compared with the dissolved
      oxygen, the substrate concentration had greater effect on the specific growth
      rate of aquatic worms, and aquatic worms can live in the environment with low
      dissolved oxygen. Furthermore, the breath test showed the oxygen uptake rate of
      aquatic worms was almost 6.39, 10.10, 11.31 and 5.74 mg x (L x g x h)(-1) from
      juvenile to decline phase, the dissolved oxygen demand of the rapid growth and
      mature stage was higher than juvenile and decline phase.

PMID- 22619961
TI  - [Feasibility study for limited filamentous bulking under low dissolved oxygen at
      different operation regimes].
AB  - Limited filamentous bulking under low dissolved oxygen (DO) is a new technology
      for energy saving and high quality effluent. In order to investigate the
      feasibility of this technology, four sequence batch reactors (SBRs) were occupied
      to operate at different regimes to stimulate different processes under low DO
      (0.5 mg/L). Sludge settleability, floc structure, pollutant removal and aerated
      energy consumption were investigated. The results showed that limited filamentous
      bulking under low DO was hard to realize in the single-stage aerobic reactors for
      they were prone to bulking severely, while it could be achieved stably in the pre
      denitrification reactors when the feed length was between 60 and 90 minutes.
      Compared with normal sludge at the same DO, limited filamentous bulking sludge
      acquired by low DO displayed its high energy-saving effect. In addition, the
      specific ammonia consumption rate of limited filamentous bulking sludge was about
      2 times higher than the one of normal sludge. On the contrary, the total nitrogen
      removal efficiency was lower. Further analysis indicated that stable limited
      sludge bulking could be achieved in a good alternative anoxic/anaerobic/aerobic
      condition without too high organic loading.

PMID- 22619962
TI  - [Air drying process of granules and characteristics of their structure].
AB  - Filamentous granules were cultivated using a sequencing batch reactor. The
      yellowish bacteria dominated granules, black fungi dominated granules and
      Microthrix parvicella dominated white smooth granules occurred in the reactor on
      the day 18, 23 and 27 respectively. Distribution of surface related free water
      and capillary water were analysis using air drying method. It was found that the
      surface related free water in the black and white filamentous granules was 79%
      and 83%, respectively, and that in the conventional bacteria granules were 64%,
      suggesting that the surface area opening ratio of surface and porosity decreased
      in the order of white, black and yellowish granules. According to the air drying
      rate in different phases of granules, it can be inferred that the white and black
      filamentous granules could rapidly exchange the substrates on the surface and
      consequently prone to be big and loose, which discourages the stability of
      granules. Additionally, the section image showed that filamentous granules were
      more porous than the black bacteria granules. Filamentous granules exhibited
      encouraging COD and nitrogen removal efficiencies. The black and white
      filamentous granules showed higher bioactivity with the oxygen up-take rate
      (SOUR) of 1.29 and 1.26 fold of the conventional yellowish granules.

PMID- 22619963
TI  - [Drying characteristics and apparent change of sludge granules during drying].
AB  - Three different weight grades of sludge granules (2.5, 5, 10 g) were dried at
      constant temperature of 100, 200, 300, 400 and 500 degrees C, respectively. Then
      characteristics of weight loss and change of apparent form during sludge drying
      were analyzed. Results showed that there were three stages during sludge drying
      at 100-200 degrees C: acceleration phase, constant-rate phase, and falling-rate
      phase. At 300-500 degrees C, there were no constant-rate phase, but due to lots
      of cracks generated at sludge surface, average drying rates were still high.
      There was a quadratic nonlinear relationship between average drying rate and
      drying temperature. At 100-200 degrees C, drying processes of different weight
      grade sludge granules were similar. At 300-500 degrees C, drying processes of
      same weight grade of sludge granules were similar. Little organic matter
      decomposed till sludge burning at 100-300 degrees C, while some organic matter
      began to decompose at the beginning of sludge drying at 400-500 degrees C.

PMID- 22619964
TI  - [Influence of accessories mixing ratio on sludge biophysical co-drying].
AB  - Parameters (temperature, water content and so on) in the process of sludge
      biophysical co-drying were studied in self-made biophysical co-drying reactor.
      The sludge: tree bark: recycled sludge was set as 7: 3: 0.5, 9: 3: 0.5, 12: 3:
      0.5 respectively. The results suggested that sludge temperature first increased
      then decreased along with drying time, water content decreased in the first 96 h,
      then had no obvious variability. While sludge: tree bark: recycled sludge was 9:
      3: 0.5, the temperature of sludge spiraling, received to max 67 degrees C at 48 h
      under three different accessories mixture ratio, and was kept for 72 h above 55
      degrees C, then spiraling, the final water content of sludge decreased from 74.1%
      to 61.8%, received the optimal water content removing rate 43.5%. Accessories
      mixing ratio had important influence on the process of sludge biophysical co
      drying, sludge with proper mixing ratio can modify the structure of sludge,
      improve sludge permeability, arouse and keep microorganic activity, which will
      enhance sludge temperature and strengthen water content removal rate.

PMID- 22619965
TI  - [Characteristics of orthophosphate adsorption on ferric-alum residuals (FARs)
      from drinking water treatment plant].
AB  - Batch tests have been used to investigate the characteristics of orthophosphate
      adsorption on ferric-alum residuals (FARs) from drinking water treatment plant.
      ICP, SEM and XRD analyses confirm that the FARs enriched in Fe and Al elements
      and presented amorphism structure. Orthophosphate sorption by the FARs can be
      described by the pseudo-second-order kinetics equation. Fine adsorption effects
      of the FARs were found under lower pH values, particularly a 40.13% drop of the
      adsorptive capacity from pH 4.6 to pH 7.6. The FARs with grain sizes of 0.6-0.9
      mm had the highest adsorption capacity of orthophosphate. Experimental data could
      be better fitted by the isotherm models of Langmuir (R2 = 0.9736) and Freundlich
      (R2 = 0.9916). The maximal adsorptive capacity reached 45.45 mg x g(-1) estimated
      from Langmuir isotherm model. Compared with other natural and industrial
      materials, FARs has relatively higher adsorption capacity. Under similar testing
      conditions, it was found that only about 10% orthophosphate could be desorbed
      from the FARs. Further study demonstrated that the mean energy of orthophosphate
      sorption on the FARs was 13.36 kJ x mol(-1) and the deltaH0 > 0, deltaS0 > 0 and
      deltaG0 < 0, which indicated that orthophosphate sorption on the FARs was a
      spontaneously endothermic chemical reaction. It can be therefore highly valued
      that the FARs may be applied to phosphate removal from wastewater and surface
      water.

PMID- 22619966
TI  - [Spectroscopy properties of dissolved organic matter in landfill leachate during
      corrosion cell-Fenton post-treatment].
AB  - To differentiate the transformation of dissolved organic matter (DOM) during
      corrosion cell-Fenton (CCF) post-treatment, the leachate was separated into five
      fractions by XAD-8 and XAD-4 resins (hydrophilic fraction, HPI; hydrophobic acid,
      HPO-A; transphilic acid, TPI-A; hydrophobic neutral, HPO-N; transphilic neutral,
      TPI-N). UV-Vis spectroscopy and fluorescence spectroscopy were used for the
      degradation analysis. Experimental results showed that DOM in landfill leachate
      reduced 61.8% of dissolved organic carbon (DOC). Especially for HPO-A and HPO-N,
      with the removal ratios were up to 74.9% and 66.5%, respectively. The predominant
      portion in the effluent was HPI (comprising 60.1% of DOC). Spectral analyses
      showed that the leachate DOM was composed of abundant condensed ring aromatic
      compounds and humic substances, with the HPO-A was the highest aromatic fraction.
      The ratio of absorbance at 253 nm and 203 nm (E253/E203) was decreased in the
      order of HPO-A > HPO-N > TPI-A > TPI-N > HPI. The unsaturated conjugated
      structures were efficiently destroyed after the CCF treatment, and the functional
      groups such as carbonyl, amine were also eliminated. The main fluorophores in
      leachate fractions were in the region of aromatic protein-like and visible fulvic
      like. The fluorescence intensity of peaks in each fraction decreased after CCF
      treatment, especially for the fulvic-like fluorescent substances. The results
      indicated that the CCF treatment was efficient to remove the hydrophobic
      fractions and reduce the complicacy of leachate effluent.

PMID- 22619967
TI  - [Measurement and preliminary human health risk assessment of representative
      organochlorines in farmed Mandarin fish].
AB  - Concentrations of representative organochlorines (OCs), including organochlorine
      pesticides (OCPs) and polychlorinated biphenyls (PCBs) in a batch of farmed
      mandarin fish from a cultivation pond in Wujiang City, Jiangsu Province, were
      determined with GC-ECD. Meanwhile, a preliminary human health risk assessment was
      conducted. Results showed that, the concentrations of
      dichlorodiphenyltrichloroethanes (DDTs), hexachlorocyclohexanes (HCHs),
      hexachlorobenzene (HCB) and PCBs in the farmed mandarin fish were in the range of
      1.3-4.57 ng/g, 0.13-1.24 ng/g, 0.07-0.44 ng/g and 0-5.22 ng/g, respectively, with
      an average value of 2.96, 0.40, 1.27 and 0.7 ng/g, respectively. These values
      were far below the corresponding residue limits set by China's Ministry of Health
      and the U.S. Food and Drug Administration, and at the low end of the global
      pollution bar. Referring to the reference values given by USEPA Integrated Risk
      Information System, calculated non-carcinogenic hazard ratios (HRs) of DDTs, HCB
      and PCBs were all <1 and carcinogenic HRs of DDTs, HCHs, HCB and PCBs were all
      >1. The results indicated that DDTs, HCHs and HCB in farmed mandarin fish did not
      have negative human health influence, but existed potential carcinogenic risk to
      humans. Compared to rural residents, urban residents were more vulnerable to
      DDTs, HCHs, HCB and PCBs threats.

PMID- 22619968
TI  - [Petroleum hydrocarbon pollution status in shellfish culture area of Sanggou Bay
      and effect on quality safety of shellfish].
AB  - Petroleum hydrocarbon concentrations in seawater, surface sediments and culture
      shellfish were investigated in shellfish culture area of Sanggou Bay from Jan. to
      Nov. in 2008. Investigation was conducted on the distribution and variation of
      petroleum hydrocarbon concentrations in seawater and sediments in the shellfish
      culture area of Sanggou Bay, as well as on the levels and the differences in
      petroleum hydrocarbon concentrations among the shellfish species. In addition,
      the petroleum hydrocarbon pollution status in the three media was evaluated and
      the effects of accumulated petroleum hydrocarbon in shellfish on the food safety
      risk were discussed. The results indicated: 1) Petroleum hydrocarbon
      concentrations in seawater in the shellfish culture area of Sanggou Bay were in
      the range of 3.61 - 98.21 microg/L; the mean values of petroleum hydrocarbon
      concentrations in sediments were in the range of 6.75-25.95 mg/kg; petroleum
      hydrocarbon concentrations in culture shellfish were in the range of 2.14- 42.87
      mg/kg; and petroleum hydrocarbon concentrations in shellfish varied largely among
      different species, with the mean values in the sequence of clam Venerupis
      variegata > oyster > scallop; 2) Monthly petroleum hydrocarbon concentrations in
      seawater and surface sediments varied significantly in Sanggou Bay shellfish
      culture area, with the highest and the lowest values of petroleum hydrocarbon
      concentrations in seawater that occurred in July and in August, respectively, and
      with the highest and the lowest values of petroleum hydrocarbon concentrations in
      surface sediments that occurred in September and in March, respectively; 3)
      According to the corresponding evaluation criteria, the petroleum hydrocarbon
      pollution status in surface sediments in Sanggou Bay shellfish culture area was
      unpolluted but the status in surface seawater was polluted. The culture shellfish
      was also polluted by petroleum hydrocarbon with different degrees among three
      species, namely, the pollution degree of clam Venerupis variegata and oyster was
      more serious than that of scallop Chlamys farreri; 4) The results of linear
      regression analysis showed that petroleum hydrocarbon concentrations in shellfish
      had a significantly positive correlation with the concentrations in seawater,
      while the linear correlation between the concentrations in shellfish and surface
      sediments was not obvious; and 5) According to the pollution level of petroleum
      hydrocarbon in shellfish, the food safety risk of three culture shellfishes in
      Sanggou Bay was relatively low.

PMID- 22619969
TI  - [Analysis of microorganism species diversity in plant intercropping models in a
      wetland system constructed for treatment of municipal sewage].
AB  - The selective culture method and PCR-DGGE technology were applied to analyze the
      number and the biodiversity of microorganism species in cells with plant
      intercropping models and without plants in different seasons in a wetland system
      constructed for treatment of municipal sewage. The results showed that the
      numbers of microorganisms were considerably larger in the cells with plant
      intercropping models than those without plants, while the number of
      microorganisms was apparently larger in summer than that in winter in all
      treatments. Along the three-sequenced treatment cells with plant intercropping
      models a "low-high-low" changing trend in the numbers of microorganisms in
      summer. The UPGMA cluster analysis showed that the treatments in the same season
      were clustered in the same branch except for a few samples in winter and the
      biodiversity index was consistently higher in summer than that in winter. Five
      different sequences (DF1-DF5) were obtained through BLAST analysis and retrieval.
      The closest known origin groups were located as Escherichia coli, Citrobacter
      sp., Proteus sp., Klebsiella oxytoca, and Burkholderia sp. respectively. The
      BLASTX comparison test showed that DF1 closely related to the activities of the
      Mycobacterium bacillus and the Bacillus amyloliquefaciens, DF2 functioned as a
      conservative potential ATP binding protein, DF3 related to the activities of the
      Bacillus cereus spore, DF4 was involved in catabolism metabolism of microorganism
      and DF5 played an important role in decomposition of organic matters.

PMID- 22619970
TI  - [Identification and denitrification characteristics of an aerobic denitrifier].
AB  - An aerobic denitrifier named F1 was isolated from grass fish pond water by BTB
      culture medium preliminary screening and denitrification activity analysis. The
      isolate was identified as Pseudomonas stutzeri through morphological feature,
      biochemical characteristics and 16S rDNA sequence analysis. Further studies
      showed that the optimal carbon resources for F1 denitrification were sodium
      acetate, sodium citrate, glucose and sucrose, with which the nitrate removal rate
      could reach 100%. When C/N ratio was above 10, the nitrogen removal rate of
      strain F1 was more than 96% and no nitrite was accumulated. The optimum condition
      for F1 growth and aerobic denitrification was temperature 30 degrees C and pH
      7.0. The F1 could tolerate dissolved oxygen level of 3.4-7.2 mg/L, and its
      nitrogen removal rate was more than 85% in 24 hours. Denitrification process of
      F1 mainly occurred in the exponential phase with NaNO3 or NaNO2 as nitrogen
      resource, and its denitrification rate reached 92.51% and 82.73% , respectively
      after 32 h of culture. These results suggest that strain F1 can denitrify NO3(-)
      or NO2(-) directly, and can tolerant a high dissolved oxygen level, and these
      characteristics make it a good candidate for aquaculture water quality treatment.

PMID- 22619971
TI  - [Screening of the aerobic simultaneous denitrobacteria and its denitrification
      characteristics].
AB  - To screen aerobic heterotrophic denitrifying bacteria from various samples and
      detect metabolites quantitatively during their denitrification process. The
      bacteria were screened by limit dilution and crossed separation. Nitrate and
      nitrite were determined using phenol disulfonic acid and N-(1-naphthyl)-ethylene
      diamine by ultraviolet spectrophotometry. The N2 was detected by gas
      chromatography. Six aerobic heterotrophic bacteria were isolated and YY-5 was
      demonstrated to be the greatest denitrifer. The degradation rate of its
      hydroxylamine oxidoreductase can reached to 70.9%. Above all, there is a good
      balance between the removal of total nitrogen and production of N2 in process. No
      N2O was produced and no nitrate or nitrite were accumulated. The high ability of
      aerobic heterotrophic bacterium YY-5 for denitrification was screened, which
      showed higher homology with Acinetobacter genus through 16S rRNA blast.

PMID- 22619972
TI  - [Responses of Ilex integra Thunb. seedlings to elevated air ozone concentration].
AB  - One-year-old Ilex integra seedlings were exposed to charcoal-filtered (CF) and
      elevated ozone (E-O3, approximately 150 microL x L(-1)) for 84 days in six open
      top chambers. Visible injury, growth parameters, pigments content, gas exchange,
      chlorophyll a fluorescence and antioxidant system were investigated during the
      growing season. At the end of experiment, foliage showed remarkable visible
      symptoms with dark-brown necrotic spots and patches which were concaved on the
      upper surface of the current-year leaves. Although relative height and diameter
      increment, total biomass and specific leaf weight (SLW) remained unaffected, E-O3
      significantly decreased the percentage of stem biomass in total biomass. E-O3
      induced significant decrease in net photosynthetic rate, chlorophyll a/b ratio
      and total phenolic compound content by 19%, 9% and 36%, respectively. However,
      stomatal conductance, intercellular CO2 concentration, chlorophyll a fluorescence
      parameters, pigment contents, MDA contents, total antioxidant capacity and total
      ascorbate content remained unaffected by E-O3. The results suggested that E-O3
      induced change in components of chlorophyll contributed to the reduction of
      photosynthesis in Ilex integra seedlings. In addition, although visible symptom
      was found during the experiment, antioxidant system, most of the physiological
      parameters and growth were not significantly affected by E-O3.

PMID- 22619973
TI  - [Effects of water-salt stresses on seedling growth and activities of
      antioxidative enzyme of Suaeda salsa in coastal wetlands of the Yellow River
      Delta].
AB  - The halophyte Suaeda salsa is the pioneer plant and is used for the degraded
      coastal wetland in Yellow River Delta. The water-salt stress is the most
      important factor for ecological restoration to degraded coastal wetland. To
      understand the adaptive mechanism of Suaeda salsa to water-salt stresses, the
      induced effects of different groundwater table depths (0, -10, -20, -30 cm) and
      salt stress (0%, 1%, 2%, 3%) on seedlings of Suaeda salsa plant were
      characterized by the growth parameters of plant height, branch number and biomass
      of different organs and biological indices of leaf chlorophyll content, the
      activities of SOD, CAT, the leaf content of MDA and protein. The results showed
      the significantly (p < 0.001) decreased height of the seedlings from -30 cm to 0
      cm of groundwater table depth, together with the decreased the number of
      branches, the biomass of leaf, shoot and root. The highest total biomass of
      single plant was (1.09 +/- 0.15) g under the condition of -30 cm water table
      depth and 0% salt stress. However, the combination of 0 cm water table depth and
      3% NaCl resulted in the biomass of (0.23 +/- 0.01) g, which was ca. 21% compared
      with the highest biomass. Similarly, the contents of leaf chlorophyll a, b and
      carotenoid were the highest under the condition of -30 cm water table depth and
      0% salt stress and lowest under the condition of 0 cm water table depth combined
      with 3% NaCl. The activities of SOD, CAT were increased significantly (p < 0.05)
      depending on the increase of salt stress. At 0 cm water table depth, the
      activities of SOD were 55.00 U/mg with 0% NaCl and 151.58 U/mg with 3% NaCl,
      respectively. The activities of SOD were decreased when the water table depth
      increased. However, the activities of CAT achieved the highest level at -30 cm
      water table depth. At 0 and -10 cm water table depth, the MDA content increased
      with the increase of salt stress. The MDA content was 0.26 mmol/g at -30 cm water
      table depth with 3% NaCl, which was approx. 28%-40% of the MDA contents compared
      with that caused by other salt stresses. These results demonstrated that Suaeda
      salsa plant could change its morphological characteristics, biomass allocation,
      and the activities of antioxidative enzymes to adapt severe environment.

PMID- 22619974
TI  - [Ecotoxicological effects of tetracycline on the seedling development of Chinese
      white cabbage (Brassica rapa L. chinensis group.) in soil].
AB  - The ecotoxicological effects of tetracycline (TC) on the early growth and
      seedlings development of Chinese white cabbage were investigated using the pot
      culture method. The results showed that the stem elongation of the cabbages was
      promoted, while the root elongation and fresh weight of the cabbages were
      inhibited by 1-100 mg/kg TC. After a 28-day exposure, the inhibition rate of root
      elongation was up to 36.0% and that of fresh weight was up to 34.6% stressed by
      100 mg/kg TC. With the exposure time of TC prolonged, the content of chlorophyll
      in leaves of the cabbage seedlings stressed by 100 mg/kg TC was significantly
      lower than that treated by other concentrations of TC, with the inhibition rate
      of chlorophyll was 21.7% - 29.0%. After a 7-day exposure to TC, the content of
      soluble protein (SP) and malondialdehyde (MDA) in the cabbage seedlings changed
      insignificantly. With the exposure time of TC prolonged, the content of SP in the
      cabbage seedlings decreased significantly, while the content of MDA increased
      significantly. Moreover, the activity of SOD, POD and CAT in Chinese white
      cabbage seedlings was inhibited by 1-100 mg/kg TC. The inhibition rates of SOD,
      POD and CAT activity exposed to 100 mg/kg TC were 33.9% - 45.3%, 33.8% - 67.7%
      and 29.6% - 57.7%, respectively. It suggested that TC has ecotoxicological
      effects on Chinese white cabbage seedlings with a chronic exposure.

PMID- 22619975
TI  - [Long-term fertilization on the behavior of aging of the phenanthrene in the
      black soil aggregates].
AB  - The soil samples were collected from the surface (0-20 cm) soil of the long-term
      fertilizer experiments in black soil areas in Northeast Location Monitoring Field
      [fertilizers and organic fertilizers (NPOM), no fertilization (NF)], and indoor
      culture method was adopted to study the behaviour of aging of the phenanthrene
      different size of soil aggregates and its contributing factors of aging source
      analysis. The results show that in the beginning of the aging > 2 mm aggregate
      fraction was a priority adsorbent, while last stage of the aging < 0.053 mm
      aggregate fraction was the preferred adsorbent. In the 120-day aging period, the
      extraction rate of 0.25-0.053 mm and 0.25-2 mm aggregate fraction had no
      significant difference. The phenanthrene residual content in undisturbed soil of
      NPOM treatment was 31.13%, while in the NF treatment residual content of
      undisturbed soil was 27.73%. Average rates of the phenanthrene aging in the NPOM
      and NF treatments was 0.26% x d(-1) and 0.23% x d(-1). The five major influence
      factors of the combination of content of the residual phenanthrene based on
      principal component analysis were analyzed, the results showed that the organic
      carbon and specific surface area were the mainly factors combined with residual
      content of phenanthrene. As a consequence, Long-term application of fertilizers
      was in favour of the aging behaviour of phenanthrene, thereby reducing the
      activity and toxicity of phenanthrene in the black soil.

PMID- 22619976
TI  - [Simulation of multimedia fate of phenanthrene in the Yangtze estuary].
AB  - A Level III fugacity model is used to simulate the concentration distribution of
      phenanthrene in air, water, sediment and plants in the Yangtze estuary. Based on
      simulation results, transfer fluxes among-phase are calculated, and also, the key
      model parameters are determined by means of sensitivity analysis. The results
      indicated that the advection of air is the main source of phenanthrene in this
      area, while the main disappeared way from the study region is the advection of
      air and water. The degradation of phenanthrene in air is the most and the
      degradation in sediment is the least. The air is the major store of phenanthrene,
      where phenanthrene was found accounts for 86.36% of the total amount, however,
      the phenanthrene concentrations is only 0.5 x 10(-7) mol x m(-3). The
      phenanthrene concentrations are higher in sediment and plants which are 1.5 x 10(
      6) mol x m(-3) and 4.4 x 10(-6) mol x m(-3), respectively. The distribute
      coefficient and the sedimentation rate of the phenanthrene control the
      distribution of the phenanthrene in each medium.

PMID- 22619977
TI  - [Characterization of polycyclic aromatic hydrocarbons contaminations in surface
      sediments from Zhalong wetland, China].
AB  - Soxhlet extraction, silica gel alumina column for separation and clean up and gas
      chromatography-mass spectrometer (GC-MS) for qualitative and quantitative
      analysis were used for study environmental behavior of 15 priority PAHs of twelve
      surface sediment samples collected from Zhalong wetland, Heilongjiang Province.
      The objectives of this study were to identify the PAHs contamination level,
      composition pattern, pollution sources and pathways, and to assess the ecological
      risk of PAHs to aquatic life in Zhalong wetland. The total concentrations of 15
      priority PAHs ranged form 31.9 to 290 ng/g (dry weight), with a mean value of 130
      ng/g. The PAHs profiles were dominated by two-to four-ring compounds which
      accounted for 90% of total PAHs. Phenanthrene, fluorine, fluoranthene, and pyrene
      represented the highest fractions in all surface sediment samples. Comparing with
      other results from wetlands and lakes in China or other countries, the PAH
      concentrations level in Zhalong wetland surface sediments were relatively low, in
      the same range of Lharu wetland. The linear regression analysis showed that the
      concentrations of PAHs were significantly correlated to the sediment total
      organic carbon (TOC) content (R2 = 0.87). PAHs contamination might mainly came
      from biomass and coal combustion. After long range atmospheric transport and
      deposition, the released PAHs finally accumulated into wetland sediment. Ecology
      risk assessment indicated that phenanthrene and fluorine had exhibited a tendency
      of accumulation on surface sediment of Zhalong wetland, which would exert
      negative toxic effect on aquatic organism.

PMID- 22619978
TI  - [Characteristics of organochlorine pesticide residues in agricultural soil of
      Chongming Island in Shanghai].
AB  - Thirty surface soil samples were collected to investigate the residue
      concentrations of organochlorine pesticides (OCPs) in agricultural soil of
      Chongming Island in July 2008. Those samples were extracted using accelerated
      solvent extraction (ASE) and determined by gas chromatography with an electron
      capture detector (GC-microECD). Results showed that the concentrations of OCPs
      (dry weight) ranged between 3.11-117.47 ng x g(-1), with mean value of 26.25 ng x
      g(-1). Two major contaminants of OCPs were DDTs and HCHs, the concentration of
      which varied from 0.14 ng x g(-1) to 77.89 ng x g(-1) and from 1.14 ng x g(-1) to
      22.43 ng x g(-1), respectively. At the same times, hexachlorobenzene (0.23-11.63
      ng x g(-1)), aldrin (0.03-0.75 ng x g(-1)), heptachlor epoxide (0.05-1.44 ng x g(
      1)), dieldrin (0.05-5.33 ng x g(-1)), endrin (ND-14.66 ng x g(-1)) and mirex
      (0.03-10.58 ng x g(-1)) could also be detected. Most of DDTs had been degraded to
      DDD and DDE, with the major compounds of DDE (about 64.7%), and the recent
      existed DDT was the residue of early input. All of the four isomers of HCHs were
      detected, and the contents of alpha-HCH (about 48.1%) and beta-HCH (about 33.4%)
      were the maximum. The highest OCPs residues appeared in the soil of farm
      cultivation compared to greenhouse cultivation and ordinary open-air cultivation.

PMID- 22619979
TI  - [Mild solvent extraction technique for the evaluation of PAHs bioavailability].
AB  - n-butanol and hydroxypropyl-beta-cyclodextrin (HPCD) were used to extract
      polyclic aromatic hydrocarbons from 9 aged agricultural fields and to assess the
      PAHs bioavailability to earthworm (Eisenia fetida). It was demonstrated that the
      high molecular weight (HMW) PAHs (> or = 4 rings) contribute the largest
      proportions (4-ring PAHs: 34.06%, 5-6 rings: 34.09%) to the contaminants in long
      term aged field soils. Moreover, the light molecular weight PAHs were easily
      accumulated in the earthworm,while the high molecular weight PAHs were hard to
      accumulate. The extraction by mild solvent correlated well with the 3 ring PAHs
      (r2 0.77-0.79) but not for the other rings PAHs (r2 <0.35), indicating that mild
      extraction may not serve as a good predictor of PAHs bioavailability to
      earthworm.

PMID- 22619980
TI  - [Content, source and speciation of heavy metal elements of street dusts in Baoji
      City].
AB  - Heavy metal concentrations in street dust of Baoji City were investigated by
      using X-Ray fluorescence spectrometry (XRF) and atomic adsorption spectrometry
      (AAS). The results show that the mean concentrations of Cu, Pb, Zn, Mn, Co, Ni,
      Cr and Cd are 123.2, 408.4, 715.1, 804.2, 15.9, 48.8, 126.7 and 5.5 microg x g(
      1), respectively, which are higher than those of the element background values of
      International, Chinese, and Shaanxi Soil, especially for Cu, Pb, Zn and Cd. The
      source of heavy metal elements in street dust of Baoji City was identifed by
      multivariate statistics analysis (correlation analysis, principal component
      analysis and cluster analysis), and the results show that Ni and Cr mainly
      originate from natural source (local soil); Cu, Pb, Mn and Co have mixed sources
      of human activities (industry and traffic) and nature (local soil); Zn and Cd
      represent traffic and industry sources. At the same time, the speciation
      characteristics of heavy metals in street dust of Baoji City were investigated by
      using the modified BCR sequential extraction procedure and ICP-MS. The results
      show that Mn, Co, Ni and Cr are dominated by residue (over 48.52%), Zn and Cd
      mainly exist in acetic acid extractable part (44.43% and 44.08%), Cu is rich in
      oxidizable (48.22%) and residual (37.65%) parts, Pb is mainly in reducible part
      (45.42%). The order of mobility of heavy metal elements is Cd (90.11%) > Pb
      (82.33%) > Zn (79.32%) > Cu (62.35%) > Mn (51.48%) > Co (29.02%) > Ni (23.62%) >
      Cr (18.68%), in which of them, Cd, Pb, Zn, Cu and Mn have stronger transformation
      (over 50%) and higher potential harm.

PMID- 22619981
TI  - [Characterization of Pb2+ adsorption on the surface of birnessite treatment with
      Na4P2O7 at different pH and the study on the distribution of Mn(III) in the
      birnessite].
AB  - Acid birnessite was treated with Na4P2O7 at pH 2, 4, 5 respectively. After the
      treatments, the species and content of manganese ion in the complex solution, and
      the variation of average oxidation state (AOS) of Mn in birnessite, and the
      amount of adsorbed Pb2+ and released Mn2+, H+ during the Pb2+ adsorption were
      investigated. The results indicate that after acid birnessite, the AOS of Mn is
      3.670 which is treated by Na4P2O7 at different pH, Mn( III) located in the layer
      edge and part of Mn(III) located in the interlayer are released to the solution
      through complexation with Na4P2O7. The content of Mn(III) in the structure of
      original birnessite is very low. Small amount of Mn(II), which accounts for 4.70%
      7.46% in the molar percentage of total released Mn, is also released
      simultaneously. The AOS of Mn of birnessites after treatment increases to 3.783
      (pH 2), 3.786 (pH 4), 3.824 (pH 5) respectively. While the crystal structure of
      birnessite does not change after treatment, the amount of Mn(III) located above
      or below vacant cation sites decreases, and the amount of H+ located above or
      below vacant cation sites goes up in the structure of birnessites. The amount of
      vacant cation sites responsible for Pb2+ adsorption increases, which lead to the
      increase of the maximum amount of adsorbed Pb2+. Additionally, the distribution
      of Mn(III) in the structure of acid birnessite is deduced. About one sixth of
      Mn(III) locates in the layer edge, and five sixths of Mn(III) locates in the
      interlayer and the non layer edge.

PMID- 22619982
TI  - [Effect of NaOH-treatment on advanced anaerobic biogasification of Spartina
      alterniflora].
AB  - In order to improve the biotransformation rate of Sparnina alterniflora, effect
      of NaOH-treatment on anaerobic dry-mesophilic digestion of Spartina alterniflora
      and feasibility of NaOH-treatment as a pretreatment of biogas residues of
      Spartina alterniflora for advanced anaerobic biogasification were conducted under
      lab-scale conditions. The results indicated that there was less improvement to
      biogas yield with NaOH-treatment and the cumulative biogas yield of Spartina
      alterniflora was 358.94 mL/g TS which was 92.42% to that of control (CK).
      However, the average methane content was improved slightly with 1.84%
      improvement. After solid-state pretreatment with 5% NaOH solution for 48 h, the
      biogas residue of Spartina alterniflora was used for advanced biogasification.
      This experiment was conducted under 35 degrees C +/- 1 degrees C with initial
      total solid loading of 8%. The cumulative biogas yield was 209.73 mL/g TS with
      70.78% of average methane content, but the biotransformation rate was only 23.29%
      which was much lower than that of Spartina alterniflora. The fermentation type
      was propionic acid type fermentation. After two-phase fermentation treatment,
      cellulose content was decreased significantly while lignin and hemicellulose
      content were increased. The crystalinity of cellulose of biogas residue decreased
      after two-phase anaerobic fermentation which was consistent to result of FTIR.
      The comprehensive analysis of experiment indicated that biogas residue of
      Spartina alterniflora was still a good material for biogas production and NaOH
      treatment was a good pretreatment for biogas production.

PMID- 22619983
TI  - [Development of colloidal gold immunochromatographic strip for rapid detection of
      domoic acid].
AB  - The colloidal gold immunochromatographic test strip was developed in order to
      establish a rapid detection assay of Domoic acid (DA) content in marine
      shellfish. The colloidal gold with particle diameter 20 nm was obtained by
      reducing gold chloride with sodium citrate. After identification by electron
      micrograph, optimum conditions for labeling were determined and colloidal gold
      was labeled by DA monoclonal antibody. The gold-labeled antibody was coated on
      some chosen glass fiber and dried. The coating antigen (DA-BSA) and Goat anti
      Mouse IgG were spotted respectively on a piece of nitrate fiber membrane as test
      line and control line. Finally the test strips were constructed and the detection
      sensitivity was measured. The results showed that, the detection limit of
      colloidal gold immunochromatographic test strip was 20 ng/mL and the whole
      analysis process could be completed within 15 min. The method established is
      sensitive and the procedure of determination is simple and quick without special
      equipment. The colloidal gold immunochromatographic test strip could be widely
      used for batch detection of domoic acid in shellfish on site and has great
      prospect for commercial development.

PMID- 22619984
TI  - Global DNA methylation and low-level exposure to benzene.
AB  - INTRODUCTION: Global genomic hypomethylation is a common event in cancer tissues
      that is frequently observed in hematopoietic malignancies, including leukemia.
      Benzene, an established leukemogen at high doses, has been suggested to induce
      hypomethylation based on investigations of DNA methylation in LINE-1 and Alu
      repetitive elements. Whether global genomic DNA methylation content is reduced in
      response to benzene exposure is still undetermined. METHODS: We measured global
      DNA methylation in 78 gasoline station attendants and 58 controls in peripheral
      blood cells using high-resolution gas chromatography-mass spectrometry. PCR
      Pyrosequencing measures of DNA methylation at Alu and LINE-1 repetitive elements,
      representing a large proportion of methylation in non-coding regions, were also
      available. Exposure markers included personal airborne benzene, and urinary
      benzene, t,t-muconic acid (t,t-MA) and S-phelylmercapturic acid. RESULTS: Mean
      global DNA methylation was 5.474 (+/- 0.083) %5mC in controls and 5.409 (+/-
      0.142) %5mC in exposed participants (p = 0.01). All methylation markers were
      negatively correlated with airborne benzene. Alu and LINE-1 methylation, but not
      global DNA methylation, were negatively associated with t,t-MA; no association
      with the other urinary biomarkers was found. Multiple linear regression analysis
      adjusted for gender and age confirmed the results of correlation analysis and
      showed a 1.6% decrease in global DNA methylation associated with being gasoline
      station attendants. Alu and LINE-1 methylation levels were not associated with
      global DNA methylation. CONCLUSION: Our results show that benzene exposure is
      associated with alterations in both global DNA and repetitive element
      methylation. Global and repetitive element methylation levels are not correlated
      in blood DNA, likely representing independent responses to benzene exposure.

PMID- 22619985
TI  - Burnout among physicians and nurses working in oncology.
AB  - BACKGROUND: The phenomenon of Burnout is an important occupational problem which
      affects those working in the "helping professions" to a greater degree since they
      have continuous and constant contact with suffering patients. AIMS: We aimed to
      assess the Burnout level and its correlation with organizational stressors.
      METHODS: The aim was achieved through administration of a questionnaire, the
      organizational check-up survey (OCS) among 80 physicians and 102 nurses working
      in a cancer institute. RESULTS: The results showed significant levels of Burnout
      (Exhaustion and Cynicism) associated with perceived discrepancy between the
      worker's values and those promoted by the hospital management, mainly among
      longer serving staff work overload reported by staff working in the intensive
      care and medical oncology departments; lack of recognition reported by permanent
      staff and also those who had no contact with the patients. CONCLUSIONS: The study
      confirmed the multiple factors involved in the phenomenon of Burnout and the
      usefulness of the OCS tool for the diagnosis and management of Burnout via
      appropriate intervention programmes. Furthermore, it also seemed to confirm the
      need to pay particular attention to the wellbeing of health professionals working
      in care and treatment of cancer patients via individual measures associated with
      other organizational measures.

PMID- 22619986
TI  - Prevalence of self-reported symptoms compatible with carpal tunnel syndrome (CTS)
      among employees at a neonatal intensive care unit: a cross-sectional study.
AB  - BACKGROUND: Carpal Tunnel Syndrome is a significant work-related disease.
      OBJECTIVE: The aim of the study was to investigate the prevalence of symptoms
      possibly related to CTS in workers in a neonatal intensive care unit. METHODS:
      The self-administered INRS questionnaire for musculoskeletal symptoms was
      distributed to all 41 employees of a neonatal intensive care unit and to an
      appropriate sample of 82 employees of a paediatric emergency department and an
      adult intensive care unit. RESULTS: Employees of the neonatal intensive care unit
      recorded a significantly higher prevalence of symptoms potentially related to CTS
      in comparison with the reference group (58.5% vs 8.3%, respectively; p < 0.001).
      Logistic regression analysis indicated that work in the neonatal intensive care
      unit was independently associated with the risk of symptoms potentially related
      to CTS. CONCLUSIONS: The results provide some evidence for a higher prevalence of
      symptoms potentially related to CTS in nursing personnel of a neonatal intensive
      care unit. Further research work is needed to prove a causal association.

PMID- 22619987
TI  - [Mortality in a cohort of railway rolling stock construction and repair workers
      in Bologna].
AB  - BACKGROUND: A private company in Bologna worked for the Italian State Railways
      (FS) from 1919 to 1998; since the early '60s it used asbestos for new carriage
      insulation and renovation of carriages already circulating which were entirely
      spray-coated with asbestos. OBJECTIVES: The study aimed to investigate all causes
      mortality, in particular mortality from asbestos-related neoplasms in blue-collar
      workers. METHODS: The cohort consisted of 1,849 people, active in 1960 or hired
      in 1960-86: 1,704 (92.2%) blue-collar workers and 145 (7.8%) white-collar
      workers. The end date of the follow up was established as 31/12/2008. Regional
      reference mortality rates were used. RESULTS: Mortality from all causes (SMR =
      1.16; 95% CI 1.08-1.25) and from malignant neoplasms (SMR = 1.20; 95% CI 1.06
      1.35) significantly exceeded expected rates. In particular, a statistically
      significant increase was observed for pleural malignant cancer (SMR = 24.43; 95%
      CI 17.37-34.37), lung cancer (SMR = 1.24; 95% CI 1.00-1.53), peritoneal cancer
      (SMR = 6.35; 95% CI 2.64-15.25) and bladder cancer (SMR = 1.71; 95% CI 1.03
      2.84). The excess lung cancer SMR was highly significant after 20 years of
      exposure and with a latency longer than 40 years. An association between pleural
      malignant cancer and duration of exposure and latency (trend test p value <
      0,0001) was observed CONCLUSION: This study on a cohort of asbestos-exposed
      workers showed an increase in lung cancer SMRs by risk that was statistically
      significant in workers exposed for at least 20 years and after 40 years of
      latency. The neoplasm of pleura was strongly associated with both duration of
      exposure and latency.

PMID- 22619988
TI  - Description of a specific bronchial provocation test for the diagnosis of
      occupational asthma due to platinum salts.
AB  - BACKGROUND: Occupational exposure to platinum salts may cause the onset of skin
      and respiratory disorders with an IgE-mediated allergic mechanism. The diagnosis
      of occupational asthma due to platinum salts was, in a small number of cases,
      achieved also via occupational specific bronchial provocation tests (sBPT), which
      until now were conducted by pouring platinum salt dusts from one tray to another
      or by direct aerosoling of hexachloroplatinate solutions into the patient's
      airways. METHODS: Here we describe an original occupational sBPT based on
      atomization of solutions of ammonium hexachloroplatinate, at increasing
      concentrations, in a 5 m3 challenge room: the starting solution is a 1:100
      dilution of the preset threshold of the patient's skin reactivity to the
      substance. In the absence of a bronchoconstrictive response, the following
      concentration is atomized (each time 10 times higher than the previous one),
      until the maximum concentration, 10(-2) M, is reached. The patient is not in the
      challenge room during atomization of the solutions, but enters when this
      operation has been completed and remains there for 15 minutes, unless he/she
      shows signs of respiratory trouble before that time. After each exposure, the
      patient is clinically monitored, with respiratory function tests at preset times,
      until at least 8 hours after the end of the exposure. RESULTS AND CONCLUSIONS:
      The test allowed identifying a respiratory hypersensitivity specifically to
      platinum as cause of asthma in two precious metal workers, with the onset of
      immediate bronchospasm in one patient and biphasic bronchospasm in the other.
      Compared to the sBPT by pouring a mixture of platinum salt dusts from one tray to
      another, the method we designed offers a better standardization of bronchial
      stimulation and, compared to direct aerosoling of hexachloroplatinate into the
      patient's airways, it has the advantage of reproducing the respiratory risk
      conditions occurring in the workplace and offers better safety guarantees for the
      patient, since it reduces the risk of onset of serious asthmatic or even systemic
      responses in subjects highly hypersensitive to this metal.

PMID- 22619989
TI  - [Temporary hearing threshold shift in policemen after firearm training].
AB  - BACKGROUND: The paper involves exposure to noise of the State Police officers
      connected with the use of firearms. The noise generated by these weapons is of
      short duration and high intensity. METHODS: The research was carried out during
      the sessions of firearm training of State Police officers to assess exposure to
      noise. RESULTS: The values of the various investigations, both audiometric and
      phonometric, carried out made it possible to demonstrate a significant exposure
      and a temporary increase in the threshold, above the frequency of 6000 Hz.
      CONCLUSION: Even taking account of the abatement from use of headphones, an
      exposure was demonstrated that was above the statutory limits, as was confirmed
      by the temporary hearing threshold shift.

PMID- 22619990
TI  - [Health promotion and obesity in the workplace among health care workers of a
      hospital in Catania (Italy)].
AB  - BACKGROUND: Italian Legislative Decree No. 81/2008 foresees the involvement of a
      "specialised physician" in activities for the promotion of health at the
      workplace. OBJECTIVES: These activities are aimed at modifying erroneous
      lifestyles (such as smoking, drinking, bad diet, etc.) which are responsible for
      serious illnesses and also for repercussions on the assessment of fitness for a
      specific task. Obesity, as we know, represents the major risk factor in the onset
      of metabolic, neoplastic, cardiovascular and respiratory diseases and also in the
      increased incidence of accidents at the workplace and sick absence. METHODS: A
      specific questionnaire was administered to 700 health care workers of a Hospital
      in Catania to estimate the incidence of factors which favour the onset of these
      diseases: factors such as familiarity, endocrinal dysfunction problems (diabetes
      mellitus, hypothyroidism), shift work and little physical exercise. RESULTS AND
      CONCLUSION: Statistical processing of the data confirmed, partially, that little
      physical exercise, hypothyroidism, diabetes mellitus, familiarity in the > 36 age
      group were the major risk factors in the onset of obesity, as reported in the
      literature. However, contrary to the literature reports, shift work did not seem
      to be a risk factor in the sample under study. A programme of rehabilitation, on
      a voluntary basis, will be offered to those workers who are overweight/obese.
      This programme will involve professionals such as nutritionists, endocrinologists
      and psychologists, and it will aim at improving workers' health conditions as
      well as their work performance.

PMID- 22619991
TI  - Combined subchronic fluoride-lead intoxication and its attenuation with the help
      of a complex of bioprotectors.
AB  - BACKGROUND: Combined toxicity of lead and fluoride has been studied
      insufficiently, and there is no known information about attempts to inhibit it
      with any bioprotectors. METHODS: Lead acetate and sodium fluoride, administered
      separately or in combination, were injected i.p. to rats at isoeffective
      sublethal doses 3 times a week for 6 weeks. Some of the rats were exposed to the
      same combination against the background of oral administration of a bioprotector
      complex (BPC) comprising pectin, glutamate, and multivitamin/multimineral
      preparations. Following exposure, functional and biochemical indices and
      histopathological examinations of the femur of exposed and control rats were
      evaluated for signs of toxicity. RESULTS: We have shown that with regard to a
      number of effects on the organism level the combined toxicity of lead and
      fluoride may be evaluated as additive or even superadditive, but lead reduces
      fluoride accumulation in the bone, and pathological changes in the bone tissue
      proved to be less marked for combined exposure compared with separate exposures.
      The BPC has been demonstrated to attenuate a range of the combined harmful
      effects of lead and fluoride, including those on the bone tissue. CONCLUSIONS: In
      spite of the fact that fluoride and lead may reciprocally attenuate their harmful
      effects on the bone tissue in case of combined exposure, they prove to be more
      toxic for soft tissues just in combination than when administered separately. The
      development of combined intoxication may be substantially inhibited by means of
      the tested set of innocuous biologically active agents.

PMID- 22619992
TI  - [The point of view of SIMLII of exposure to silica and tumors risk].

PMID- 22619993
TI  - [Biomarker research for a clinical setting].

PMID- 22619994
TI  - [The concept and history of biomarker].
AB  - Biomarker is a characteristic objectively measured and an indicator of biological
      process. This term indicates not only biological substance, for example protein,
      ribonucleic acid but also imaging assays. Disease biomarkers have been applied to
      a wide variety of clinical areas, including oncology, metabolic disorders,
      neurological disease and immune dysregulation. In recent years because of the
      progress of analysis technology, new biomarkers continue to be devised and used
      as diagnostic, predictive, prognostic, and toxic marker. In drug development
      area, biomarkers are used as surrogate endpoint to substitute for a clinical
      endpoint and needed for rational drug development. Here, we summarize the concept
      and history of biomarker.

PMID- 22619995
TI  - [Research and development for cancer biomarker].
AB  - Cancer is a very heterogeneous group of diseases whose pathogenesis,
      aggressiveness, metastatic potential, and response to treatment can be different
      among individual patients. Personalized medicine should be practiced to take care
      of these cancer patients to improve medical care quality and reduce health care
      cost. Biomarker discovery and development are one of the cores of personalized
      medicine for cancer, which encompasses screening, early diagnosis, prognosis,
      cancer stratification, prediction of treatment efficacy and adverse reaction.
      Thanks to the emergence of new innovated high-throughput technologies, biomarker
      research and development are now efficiently performed in many laboratories and
      several candidates have been identified and applied to cancer patient care. To
      perform biomarker research and development more efficiently, we need to determine
      the endpoint of biomarkers clearly, to obtain a number of high-quality clinical
      samples with solid clinical information, and to performed high-throughput
      analysis in non-bias way. Once we discover biomarker candidates, we definitely
      need to validate their potential as biomarkers by analyzing independent sample
      sets with more accurate and focusing methods. Recently, pharmaceutical companies
      are trying to develop a drug-specific companion biomarker kits that can predict
      the efficacy or side effect of drugs in the early stage of development of anti
      cancer drugs.

PMID- 22619996
TI  - [Epigenomic markers for tumors].
AB  - Accumulation of epigenomic aberrations plays a critical role in tumorigenesis,
      both in tumor initiation and progression. Development of epigenomic markers can
      therefore be useful in determination of tumor risk of apparently normal cases, or
      in classifying tumor cases in relation to etiology, prognosis or therapy
      response. Loss of imprinting of IGF2 is an epigenetic aberration that exists in
      normal tissues and modifies tumor risk, and is a possible therapy target for
      tumor risk management. Thanks to development of quantitative and comprehensive
      analysis tools for DNA methylation, it becomes possible to epigenotype tumors,
      i.e., classification of tumors using epigenomic information, by unsupervised
      hierarchical clustering. Gastric cancer is epigenotyped in relation to etiology
      such as EB virus infection, and colorectal cancer is epigenotyped in relation to
      oncogene mutation statuses, suggesting distinct molecular mechanisms in
      colorectal tumorigenesis.

PMID- 22619997
TI  - [Biomarker development by cancer proteomics].
AB  - Cancer is a genetically and clinically diverse disease, and biomarkers are
      required to optimize the therapeutic strategies. Proteome is a functional
      translation of genome, directly regulating cancer phenotypes. Biomarker studies
      have been conducted by the proteomic approach. By the proteomic approach, we
      developed a novel prognostic biomarker in gastrointestinal stromal tumor(GIST).
      In GIST, adjuvant imatinib mesylate after resection improved recurrence-free
      survival. A prognostic biomarker is required to select the patients for the
      treatment with imatinib mesylate. Proteomic approach using two-dimensional
      difference gel electrophoresis(2D-DIGE) identified pfetin as a biomarker for
      favorable prognosis. Multi-institutional validation study by immunohistochemistry
      established the prognostic values of pfetin in GIST. Pfetin will be applicable
      for a novel prognostic modality.

PMID- 22619998
TI  - [Biomarkers for cancer immunotherapy].
AB  - Immune-biomarkers and -assays are important for development of cancer
      immunotherapy to select the patients who are expected to respond to immunotherapy
      before or early after immunotherapy, to monitor immune induction following
      immunotherapy, and to evaluate anti-tumor effects early after immunotherapy.
      Comprehensive immune-evaluation including positive and negative immune responses
      against cancer cells and identification of blood biomarkers which reflect immune
      conditions in tumor microenvironment are required although direct evaluation of
      tumor tissues can be possible for some patients. Importance of immune responses
      has recently been recognized even for standard cancer treatments including
      chemotherapy and molecular target therapy. Therefore, immunological biomarkers
      may be useful for any cancer treatment.

PMID- 22619999
TI  - [Perspective of proteomic studies for discovering biomarkers of diabetes and
      obesity].
AB  - The prevalence of diabetes is rapidly increasing worldwide, leading to an
      increasing risk of microangiopathic complications. To identify biomarkers of
      diabetic microangiopathy that are useful for prevention and early treatment of
      diabetic complications, proteomic analyses of clinical samples from diabetic
      patients have been performed. However, as diabetes is a systemic disease, it is
      difficult to define the pathologic conditions and foci causing changes in
      proteomic profile of clinical samples from diabetics. An approach using multiple
      reaction monitoring may be useful to systemically identify diabetic
      microangiopathy biomarkers from blood and urine samples from diabetic patients.

PMID- 22620000
TI  - [Clinical significance of BNP as a biomarker for cardiac disease--from a
      viewpoint of basic science and clinical aspect].
AB  - BNP was discovered in the porcine brain extract in 1988. Subsequent studies have
      demonstrated that BNP is a cardiac hormone in humans. Plasma level of BNP is
      increased in patients with heart failure more than ANP. Therefore, BNP
      measurements as a biomarker for heart failure spread all over our country and all
      over the world. Now the guideline in the world recognizes that BNP is a useful
      biomarker for diagnosis for acute and chronic heart failure. However, the
      usefulness of "BNP-guided therapy for heart failure" is still controversial at
      present, because randomized-controlled studies have shown the neutral results.
      Although more than twenty years have passed since its discovery, recent studies
      have shown the new findings in BNP research. I describe here the recent advance
      of BNP research.

PMID- 22620001
TI  - [Searching for biomarkers to diagnose dementia].
AB  - A decrease in the concentration of amyloid beta-protein-42 and an increase in
      that of tau or phosphorylated tau in addition to volumetry on MRI and amyloid
      imaging by PET are available biomarkers. However, we need better biomarkers to
      detect very early stage of Alzheimer disease to develop disease modifying drugs,
      which should be used 10 or 15 years prior to emergence of clinical symptoms. In
      terms of biomarkers for other dementing neurodegenerative diseases, including
      synucleinopathies such as dementia with Lewy bodies and multiple system atrophy,
      and tauopathies such as progressive supranuclear palsy, corticobasal
      degeneration, synuclein, TDP-43, progranulin and tau may be candidate proteins
      for possible biomarkers for these diseases.

PMID- 22620002
TI  - [Diagnostic biomarkers in inflammatory bowel disease].
AB  - Inflammatory bowel diseases (IBD), which includes ulcerative colitis and Crohn's
      disease, are chronic intestinal disorders of unknown etiology. The diagnosis of
      IBD is based upon clinical history, endoscopic, and histological findings;
      however, accurate diagnosis can still be difficult with these current
      methodologies. Recent advances in molecular techniques in proteomics and genetic
      analysis have driven the discovery of novel IBD biomarkers and genetic
      susceptibility factors that may facilitate the diagnosis of IBD. In the future,
      biomarkers will play a key role in the diagnosis of IBD and the development of
      individual courses of treatment.

PMID- 22620003
TI  - [Development of biomarker for detecting cartilage degradation in osteoarthritis].
AB  - Now, It is becoming known that the mechanisms of cartilage matrix destruction
      such as roles of degradative enzymes including matrix metalloproteinase (MMP),
      aggrecanase, and cathepsin K and cytokines. For prevention of progression of
      cartilage destruction, it is important to develop the reliable biomarkers to
      detect the early stage of cartilage destruction. We reviewed the specific
      destructive products of type II collagen, major component of cartilage matrix,
      generated by collagenases and cathepsin K as well as those of aggrecan generated
      by MMPs and aggrecanase. The biomarker could be useful tool not only to
      understand the progression of joint destruction in osteoarthritis and rheumatoid
      arthritis but also to develop new treatment.

PMID- 22620004
TI  - [Biomarker for colorectal cancer].
AB  - Discovery of usable molecular biomarkers is the step closer to a realization of
      personalized therapy for patients with colorectal cancer(CRC). Herein we present
      an update of the most recent data on promising biological prognostic and/or
      predictive markers, including microsatellite instability(MSI) and KRAS/BRAF
      mutations. Additionally, we propose a new genetic classification for CRC based on
      MSI and KRAS/BRAF mutation status (a 2 x 3 matrix). The 2 x 3 matrix is
      constructed of 6 cells that are made by [MSI/non-MSI] x [BRAF mutant/KRAS
      mutant/wild type of the both genes]. All of CRC including Lynch syndrome could be
      classified without overlapping into the 6 cells. More interestingly, each cell
      has each promising biological prognostic and/or predictive feature, which will
      help clinicians to make personalized treatment strategy for each CRC patient.

PMID- 22620005
TI  - [Diagnostic and therapeutic biomarkers for lung cancer patients].
AB  - Identification of sensitive biomarkers predictive of diagnosis, prognosis and
      drug sensitivity could have a clinically significant impact on non-small cell
      lung cancer (NSCLC) treatment strategies. Recently, molecular-targeted therapies
      have been developed for NSCLC treatment. NSCLC patients with epidermal growth
      factor receptor (EGFR) gene mutations have shown a dramatic response to EGFR
      tyrosine kinase inhibitors (EGFR-TKI) such as gefitinib and erlotinib. In
      addition, target therapies against echinoderm microtubule-associated protein-like
      4-anaplastic lymphoma kinase (EML4-ALK) fusion protein present in approximately
      5% of the Japanese patients with adenocarcinomas are currently under development.
      In this paper, we reviewed diagnostic and therapeutic biomarkers for lung cancer
      patients.

PMID- 22620006
TI  - [Which biomarkers can we use?].
AB  - Gene array testing defined the intrinsic biological subtypes including"luminal
      A", "luminal B", "HER2-enriched" and "basal" within breast cancer. These subtypes
      may be approximated using clinicopathological immunochemistry rather than gene
      expression array criteria. These subtypes have different epidemiological risk
      factors, different natural histories, and different response to systemic and
      local therapies. Systemic therapy recommendations follow the subtype
      classification. "Estrogen receptor", "progesterone receptor", "human epidermal
      growth factor receptor 2" and "Ki67" are the most important biological markers to
      classify the subtypes and predict the prognosis and the response to the therapy.
      The new targeting therapy will require new biomarkers.

PMID- 22620007
TI  - [Tumor markers for hepatocellular carcinoma].
AB  - Three tumor markers for hepatocellular carcinoma (HCC) are available in Japan:
      alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonists-II
      (PIVKA-II), and Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein
      (AFP-L3). Although AFP has drawbacks in its specificity, it is widely utilized in
      treatment evaluation and prognosis prediction. PIVKA-II is a unique marker that
      does not correlate with AFP value and can predict microvascular invasion. AFP-L3
      is a highly specific marker and strong predictor of poor prognosis. These three
      markers are indispensable in every aspect of clinical practice of hepatocellular
      carcinoma including surveillance, diagnosis, treatment evaluation, and prognosis
      prediction.

PMID- 22620008
TI  - [New biomarkers for the prostate cancer].
AB  - Prostate-specific antigen (PSA) has been widely used as a biomarker for prostate
      cancer detection and progression. However, PSA has limitations in terms of
      predicting the prognosis in specific cases of prostate cancer because it does not
      reflect cancer biology. Due to the development of new techniques in the fields of
      genomics and proteomics, many new biomarkers have been discovered in the last
      several years. In this review, we described some of these new and promising
      biomarkers including gene and protein markers, cytokines and circulating tumor
      cells. Moreover, we introduced our proteomic-based findings in our search for new
      prostate cancer biomarkers.

PMID- 22620009
TI  - [Hematopoietic malignancy (leukemia, malignant lymphoma, multiple myeloma)].
AB  - Hematopoietic malignancies, including leukemia, lymphoma and multiple myeloma,
      are classified and predicted a prognosis by morphologic, cytogenetic and
      molecular features. With advances in molecular targeted therapy and hematopoietic
      stem cell transplantation, monitoring of minimal residual disease (MRD) is
      required for evaluation of an optimal response to therapy and early detection of
      disease relapse. Analysis of immunophenotypes and chimeric fusion genes
      characteristic for hematopoietic malignant cells are clinically useful biomarkers
      to classify into subtype at diagnosis and monitor MRD. On the other hand, serum
      markers reflecting tumor burden are clinically useful to monitor the disease
      progression in hematopoietic malignancies: e.g., LDH and soluble IL-2 receptor
      for lymphoma; M-protein and free light chain for multiple myeloma.

PMID- 22620010
TI  - [Atherosclerosis (hypertension)].
AB  - Many studies have shown that atherosclerosis is an inflammatory disease.
      Therefore biomarkers reflecting the magnitude of inflammation can be also a good
      marker for atherosclerosis. Clinical studies have shown that high sensitive C
      reactive protein (hsCRP) is one of a promising biomarker for presence or
      progression of atherosclerosis. Markers for dyslipidemia, diabetes, hypertension,
      and injury of endothelium and smooth muscle cells also have links to
      atherosclerosis. Regarding hypertension, microalbuminuria and cystatin C levels
      show the degree of future risk for atherosclerosis. Atherosclerosis is
      pathologically so complicated that no single biomarker can be perfect and it is
      essential for every clinician to use several appropriate biomarkers together to
      diagnose the disease.

PMID- 22620011
TI  - [Clinical biomarkers for diabetes mellitus].
AB  - Diabetes mellitus is a group of diseases associated with various metabolic
      disorders, the main feature of which is chronic hyperglycemia due to insufficient
      insulin action. Confirmation of chronic hyperglycemia is essential for the
      diagnosis of diabetes. HbA1c level is considered an indicator of the average
      blood glucose level over the last 1 to 2 months. According to the recent revision
      of diagnosis criteria for diabetes, in addition to the earlier listed plasma
      glucose values, HbA1c has been given a more prominent position as one of the
      criteria for diabetic diagnosis. Other biomarkers such as glycoalbumin and 1.5
      Anhydro-D-glucitol are also useful for evaluating glycemic control. In this
      chapter, we provide an overview of each clinical biomarkers for diabetes.

PMID- 22620012
TI  - [Dyslipidemia].
AB  - Low-density lipoprotein (LDL) cholesterol is the most established risk factor for
      atherosclerotic disease such as coronary artery disease and cerebrovascular
      disease. High-density lipoprotein (HDL) cholesterol and nonHDL-C as well as small
      dense LDL, Remnant like particles cholesterol (RLP-C) and oxidized LDL are the
      secondary risk factors for atherosclerosis. It is important to integrate and
      control these risk factors for the prevention of atherosclerosis as a real
      endpoint of diagnosis and treatment of dyslipidemia.

PMID- 22620013
TI  - [Biomarker of dementia: clinical and preclinical diagnosis].
AB  - Recent advances in biomarker studies on dementia are summarized here. CSF
      Abeta40, Abeta42, total tau and phosphorylated tau are most sensitive biomarkers
      for diagnosis of Alzheimer's disease (AD) and prediction of onset of AD from mild
      cognitive impairment (MCI). Based on this progress, new diagnostic criteria for
      AD, MCI and preclinical AD were proposed by National Institute of Aging (NIA) and
      Alzheimer' s Association. In these new criteria, progress in biomarker
      identification and amyloid imaging studies in the past 10 years have added
      critical information. Huge contributions of basic and clinical studies have
      established clinical evidence supporting these markers. Based on this progress,
      essential therapy for cure of AD is urgently expected.

PMID- 22620014
TI  - [Disease biomarkers for CKD].
AB  - As novel urinary biomarkers for kidney injury, neutrophil gelatinase-associated
      lipocalin (Ngal), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding
      protein(L-FABP) et al. have emerged. Recent studies elucidated their usefulness
      in chronic kidney disease and acute kidney injury. Meanwhile, the understanding
      of clinical significance of albuminuria, a classical biomarker, has changed as
      well. In this review, the progress and current status of urinary biomarker
      research in the field of chronic kidney disease will be described and future
      problems to be solved will be discussed.

PMID- 22620015
TI  - [Biomarkers in the diagnosis and therapy of inflammatory bowel diseases].
AB  - Serologic and fecal biomarkers can be used in the diagnosis and management of
      inflammatory bowel disease (IBD). Antibodies against Saccharomyces cerevisiae and
      perinuclear antineutrophil cytoplasmic proteins have been used in diagnosis of
      IBD, to distinguish Crohn's disease from ulcerative colitis, and to predict the
      risk of complications of Crohn's disease. C-reactive protein has been used to
      assess inflammatory processes and predict the course of IBD progression. Fecal
      markers have been studied for their ability to identify patients with IBD, assess
      disease activity, and predict relapse. We recently reported that oligosaccharides
      in IgG and leucin rich alpha 2-glycoprotein are potential biomarkers of IBD. This
      review addresses the potential for biomarkers to improve treatment strategies and
      challenges to their use.

PMID- 22620016
TI  - [The designs of exploratory biomarker study].
AB  - With the progress of molecular biology and other disciplines, biomarkers are
      becoming increasingly important in both drug discovery and development. Several
      critical issues, including scientific rationale, study design, marker assessment,
      cost and feasibility should be carefully considered in the validation of
      biomarkers through clinical research. Here, we highlight several important
      aspects related to the design for clinical researches which incorporate
      biomarkers. First, we define the term "biomarker" and illustrate the difference
      between prognostic and predictive markers. Second, in exploratory clinical
      studies, we focus on issues related to study design for screening and evaluating
      biomarkers. Finally, we review the design of confirmatory clinical trials for new
      treatments and companion biomarker diagnostic tests.

PMID- 22620017
TI  - [Biomarkers of stress and fatigue].
AB  - A questionnaire based survey has been commonly used for the assessment of
      psychological stress and stress-related diseases. Development of a quantitative
      approach using a non-invasive sample (i.e., saliva, hair or nails) is highly
      desirable to measure chronic stress. This paper gives a brief explanation of
      subjective and objective (i.e., physiological signals, and biological markers)
      methods for stress assessment. Furthermore, it focuses particularly on the
      current knowledge about the biomarker candidates of chronic psychological stress
      and chronic fatigue syndrome (CFS). Psychological stress is known to stimulate
      the autonomic nervous, endocrine, and immune systems. Since chronic stress is
      associated with suppression of a variety of immune parameters, some immune
      markers are potentially useful.

PMID- 22620018
TI  - [CSF biomarkers in children with acute encephalopathy syndrome].
AB  - Viral infection-associated acute encephalopathy in children is a clinical
      syndrome with high mortality and neurological sequelae. Its main symptoms of
      acute phase are impaired consciousness and convulsive status epilepticus with
      hyperpyrexia. Acute encephalopathy with biphasic seizures and late reduced
      diffusion (AESD) is characterized clinically by biphasic seizures and late MRI
      abnormalities such as reduced subcortical diffusion. Despite the intensive care,
      patients with AESD often have severe neurological impairment and it is very
      difficult to distinguish AESD from febrile seizures in the early phase. Although
      there is currently no specific biomarker for early diagnosis of acute
      encephalopathy syndrome, we believe tau protein and 8-hydroxy-2'-deoxyguanosine
      (8-OHdG) are potential biomarkers which could be useful in following the clinical
      course and monitoring the efficacy of therapies.

PMID- 22620019
TI  - [Sporadic inclusion body myositis in Japan].
AB  - Sporadic inclusion body myositis (sIBM), the most common form of myopathy with
      inflammation in those over the age of 50 in Western countries, is an intractable
      and progressive skeletal muscle disease of unknown cause and without effective
      treatment. Muscle biopsy typically reveals endomysial inflammation, invasion of
      mononuclear cells into non-necrotic fibers and rimmed vacuoles, suggesting
      inflammation and degeneration are co-existed in the pathogenesis. We estimated
      the prevalence of sIBM in Japan is 9.83 per million in 2003 and an increase in
      the number of sIBM in Japan in the decade. In this review, we discuss the
      diagnostic criteria sIBM in Japan, and describe available treatments and
      promising new therapeutic strategies. We also provide an update on the current
      understanding of sIBM pathogenesis.

PMID- 22620020
TI  - [Delirium, insomnia in hospitalization and ramelteon].
AB  - Ramelteon acts on a highly selective melatonin (MT1/MT2) receptor agonist. During
      delirium in postoperative and critically ill patients, a disruption of the sleep
      wake cycle is frequently observed. Melatonin has a key role in the regulation of
      the sleep-wake cycle, so this raised the hypothesis that alterations in the
      metabolism of melatonin might play an important role in the development of
      delirium. Ramelteon and exogenous melatonin may have a prophylactic treatment for
      frail older persons at high risk for delirium that is safe, effective, and easily
      implementable in daily practice. However, there is currently insufficient
      evidence that ramelteon and exogenous melatonin is effective in preventing or
      treating postoperative delirium and sleep disorders in the critically ill
      patient.

PMID- 22620021
TI  - [The 39th scientific meeting: perspectives of internal medicine; the cutting edge
      of treatment of medical disorders encountered in clinical practice; 1. Preface].

PMID- 22620022
TI  - [The 39th scientific meeting: perspectives of internal medicine; the cutting edge
      of treatment of medical disorders encountered in clinical practice; 2. Recent
      progress on clinical management for adrenal disorders].

PMID- 22620023
TI  - [The 39th scientific meeting: perspectives of internal medicine; the cutting edge
      of treatment of medical disorders encountered in clinical practice: 3. Approach
      to chronic kidney disease].

PMID- 22620024
TI  - [The 39th scientific meeting: perspectives of internal medicine; the cutting edge
      of treatment of medical disorders encountered in clinical practice; 4. Current
      treatment of hypertension].

PMID- 22620025
TI  - [The 39th scientific meeting: perspectives of internal medicine; the cutting edge
      of treatment of medical disorders encountered in clinical practice; 5. Recent
      paradigm for management of atrial fibrillation].

PMID- 22620026
TI  - [The 39th scientific meeting: perspectives of internal medicine; the cutting edge
      of treatment of medical disorders encountered in clinical practice; 6. Incretin
      for treatment of type 2 diabetes].

PMID- 22620027
TI  - [The 39th scientific meeting: perspectives of internal medicine; the cutting edge
      of treatment of medical disorders encountered in clinical practice; 7.
      Pathophysiology and treatment of COPD].

PMID- 22620028
TI  - [The 39th scientific meeting: perspectives of internal medicine: the cutting edge
      of treatment of medical disorders encountered in clinical practice; 8. Recent
      advances in the treatment of inflammatory bowel diseases].

PMID- 22620029
TI  - [The 39th scientific meeting: perspectives of internal medicine; the cutting edge
      of treatment of medical disorders encountered in clinical practice; 9. Progress
      in RA management].

PMID- 22620030
TI  - [The 39th scientific meeting: perspectives of internal medicine; the cutting edge
      of treatment of medical disorders encountered in clinical practice; 10. Summary].

PMID- 22620031
TI  - [Programs for continuing medical education: A session; 1. NSAID-induced
      gastrointestinal injury].

PMID- 22620032
TI  - [Programs for continuing medical education: A session; 2. Pathophysiology and
      treatment of nonalcoholic fatty liver disease].

PMID- 22620033
TI  - [Programs for continuing medical education: A session; 3. Pathogenesis and
      treatment of cerebellar ataxia-recent progresses].

PMID- 22620034
TI  - [Programs for continuing medical education: A session; 4. Clinical manifestation
      of cervical spondylosis].

PMID- 22620035
TI  - [Programs for continuing medical education: A session; 5. New era of diabetes
      treatment].

PMID- 22620036
TI  - [Programs for continuing medical education: A session; 6. Endocrine
      hypertension].

PMID- 22620037
TI  - [Programs for continuing medical education: A session; 7. Current topics of
      asthma treatment--anti-IgE therapy].

PMID- 22620039
TI  - [Programs for continuing medical education: A session; 9. Comprehension and
      coping with dementia].

PMID- 22620038
TI  - [Programs for continuing medical education: A session; 8. Practice of rheumatoid
      arthritis].

PMID- 22620040
TI  - [Programs for continuing medical education: B session; 1. Treatment of
      hypertension: evaluation and management of resistant hypertension].

PMID- 22620041
TI  - [Programs for continuing medical education: B session; 2. Guideline-directed
      treatments of atrial fibrillation and premature ventricular contraction].

PMID- 22620042
TI  - [Programs for continuing medical education: B session; 3. Laboratory findings of
      hematological diseases].

PMID- 22620043
TI  - [Programs for continuing medical education: B session; 4. Human T-cell leukemia
      virus type 1 infection].

PMID- 22620044
TI  - [Programs for continuing medical education: B session; 5. Clinical approach to
      infectious diseases utilizing physical examinations].

PMID- 22620045
TI  - [Programs for continuing medical education: B session; 6. Treatment of acute
      bacterial meningitis in adults based on Japanese guideline for the management of
      bacterial meningitis].

PMID- 22620046
TI  - [Programs for continuing medical education: B session; 7. Water and electrolyte
      disorders].

PMID- 22620047
TI  - [Programs for continuing medical education: B session; 8. Pneumonia and its
      radiological findings].

PMID- 22620048
TI  - [Programs for continuing medical education: B session; 9. Pitfalls for internists
      in the outpatient clinic].

PMID- 22620049
TI  - [Case report; A case of IgG4-related tubulointerstitial nephritis complicated
      nephrotic syndrome].

PMID- 22620050
TI  - [Case report; Plummer disease associated with acromegaly].

PMID- 22620051
TI  - [Case report; composite lymphoma of adult T-cell leukemia/lymphoma and diffuse
      large B-cell lymphoma with abrupt onset of ascites and pleural effusion].

PMID- 22620052
TI  - [Case report; A case of overwhelming postsplenectomy infection with purpura
      fuluminans due to pneumococcal infection].

PMID- 22620053
TI  - [Case report; a case of acute rheumatic fever in an adult].

PMID- 22620054
TI  - [Case report; a case of secondary pseudogout caused by vitamin D].

PMID- 22620055
TI  - [The cutting-edge of medicine; smoking and coronary artery disease].

PMID- 22620056
TI  - [The cutting-edge of medicine; Japanese new guidelines for nursing and healthcare
      associated pneumonia].

PMID- 22620057
TI  - [Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011.
      Research Program of Intractable Disease provided by the Ministry of Health,
      Labor, and Welfare of Japan].

PMID- 22620260
TI  - Electrospun porous structure fibrous film with high oil adsorption capacity.
AB  - A low-cost, high-oil-adsorption film consisting of polystyrene (PS) fibers is
      fabricated by a facile electrospinning method. Different fiber diameter and
      porous fiber's surface morphology play roles in oil adsorption capacity and
      oil/water selectivity. The results showed that oil adsorption capacity of PS oil
      sorbent film with small diameter and porous surface structure for diesel oil,
      silicon oil, peanut oil and motor oil were approximate to 7.13, 81.40, 112.30,
      and 131.63 g/g, respectively. It was higher than normal fibrous sorbent without
      any porous structure. The thinner porous PS oil sorbent also had excellent
      oil/water selectivity in the cleanup of oil from water. 

PMID- 22620259
TI  - Nitrite reductase activity of nonsymbiotic hemoglobins from Arabidopsis thaliana.
AB  - Plant nonsymbiotic hemoglobins possess hexacoordinate heme geometry similar to
      that of the heme protein neuroglobin. We recently discovered that deoxygenated
      neuroglobin converts nitrite to nitric oxide (NO), an important signaling
      molecule involved in many processes in plants. We sought to determine whether
      Arabidopsis thaliana nonsymbiotic hemoglobins classes 1 and 2 (AHb1 and AHb2,
      respectively) might function as nitrite reductases. We found that the reaction of
      nitrite with deoxygenated AHb1 and AHb2 generates NO gas and iron-nitrosyl
      hemoglobin species. The bimolecular rate constants for reduction of nitrite to NO
      are 19.8 +/- 3.2 and 4.9 +/- 0.2 M(-1) s(-1), respectively, at pH 7.4 and 25 
      degrees C. We determined the pH dependence of these bimolecular rate constants
      and found a linear correlation with the concentration of protons, indicating the
      requirement for one proton in the reaction. The release of free NO gas during the
      reaction under anoxic and hypoxic (2% oxygen) conditions was confirmed by
      chemiluminescence detection. These results demonstrate that deoxygenated AHb1 and
      AHb2 reduce nitrite to form NO via a mechanism analogous to that observed for
      hemoglobin, myoglobin, and neuroglobin. Our findings suggest that during severe
      hypoxia and in the anaerobic plant roots, especially in species submerged in
      water, nonsymbiotic hemoglobins provide a viable pathway for NO generation via
      nitrite reduction.

PMID- 22620261
TI  - Novel substituted benzothiophene and thienothiophene carboxanilides and
      quinolones: synthesis, photochemical synthesis, DNA-binding properties, antitumor
      evaluation and 3D-derived QSAR analysis.
AB  - A series of new N,N-dimethylaminopropyl- and 2-imidazolinyl-substituted
      derivatives of benzo[b]thienyl- and thieno[2,3-b]thienylcarboxanilides and
      benzo[b]thieno[2,3-c]- and thieno[3',2':4,5]thieno[2,3-c]quinolones were
      prepared. Quinolones were prepared by the reaction of photochemical
      dehydrohalogenation of corresponding anilides. Carboxanilides and quinolones were
      tested for the antiproliferative activity. 2-Imidazolinyl-substituted derivatives
      showed very prominent activity. By use of the experimentally obtained antitumor
      measurements, 3D-derived QSAR analysis was performed for the set of compounds.
      Highly predictive 3D-derived QSAR models were obtained, and molecular properties
      that have the highest impact on antitumor activity were identified.
      Carboxanilides 6a-c and quinolones 9a-c and 11a were evaluated for DNA binding
      propensities and topoisomerases I and II inhibition as part of their mechanism of
      action assessment. The evaluated differences in the mode of action nicely
      correlate with the results of the 3D-QSAR analysis. Taken together, the results
      indicate which modifications of the compounds from the series should further
      improve their anticancer properties.

PMID- 22620264
TI  - Future treatment strategies for celiac disease.
AB  - INTRODUCTION: Ingestion of dietary gluten in wheat, rye and barley by celiac
      patients leads to small-bowel mucosal villous atrophy, crypt hyperplasia and
      massive inflammation, often coupled with clinical symptoms and signs. Currently,
      the only effective treatment is a strict life-long gluten-free diet excluding all
      gluten-containing food products. In view of the extremely restricted nature of
      the diet, new treatment options would clearly be desirable. AREAS COVERED: The
      improved understanding of celiac disease pathogenesis has enabled researchers to
      suggest alternative strategies to treat the disorder. This review covers current
      approaches toward developing an appropriate drug and discusses the possible
      problems associated with these approaches. EXPERT OPINION: Phase II clinical
      trials are already ongoing to test the efficacy of novel alternative treatments
      for celiac disease. Before any of the candidates can enter Phase III trials,
      however, researchers must develop novel reliable non-invasive surrogate markers
      for intestinal injury and disease activity which also accurately reflect patient
      related outcomes. Any novel medication for celiac disease should be as effective
      and safe as the gluten-free diet, and this constitutes a challenge for drug
      development. It is thus likely that the first medication entering the market will
      be supplementary to rather than substitute the gluten-free diet.

PMID- 22620265
TI  - Monitoring height and weight: findings from a developmental paediatric service.
AB  - AIM: To assess the recording of weight and height in children with disabilities
      and identify subgroups at risk of being either underweight or overweight.
      METHODS: A retrospective clinical audit was undertaken within the Department of
      Developmental Medicine at The Royal Children's Hospital, Melbourne. Most recent
      weight and height measurements and data about the child's underlying condition
      were collected from the medical records of children attending a clinical
      appointment over a 3-month period. Primary medical diagnosis, age, gender, mode
      of feeding and ability to ambulate were recorded. Body mass index was calculated
      and corrected for age and gender. RESULTS:  Study sample size was 583 (356
      males), mean age was 8.25 years (range 2.8-17.4 years). Body mass index could be
      calculated for 48%. Height was less commonly measured in those with severe
      physical impairments. A survey of barriers to weight and height measurement
      showed that the main barrier to measuring height was practical difficulties. The
      percentage of children classified as overweight/obese was 26.6% and this was
      associated with intellectual disabilities, moderately impaired ambulation, older
      age and female gender; 13.5% of the study group was underweight, the majority of
      whom were non-ambulant. CONCLUSIONS:  Although significant rates of underweight
      and overweight were identified in children with a range of disabilities within
      our service, monitoring of weight status was suboptimal. Despite this, data
      indicate that specific subgroups of children with disability appear at risk of
      being either overweight or underweight. Where height cannot be measured, other
      anthropometric measures such as waist circumference may be useful in the
      assessment of children with disabilities.

PMID- 22620267
TI  - Bisphenol S in urine from the United States and seven Asian countries: occurrence
      and human exposures.
AB  - As concern regarding the toxic effects of bisphenol A (BPA) grows, BPA in many
      consumer products is gradually being replaced with compounds such as bisphenol S
      (BPS). Nevertheless, data on the occurrence of BPS in human specimens are
      limited. In this study, 315 urine samples, collected from the general populations
      in the United States, China, India, Japan, Korea, Kuwait, Malaysia, and Vietnam,
      were analyzed for the presence of total BPS (free plus conjugated) concentrations
      by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS).
      BPS was detected in 81% of the urine samples analyzed at concentrations ranging
      from below the limit of quantitation (LOQ; 0.02 ng/mL) to 21 ng/mL (geometric
      mean: 0.168 ng/mL). The urinary BPS concentration varied among countries, and the
      highest geometric mean concentration [1.18 ng/mLor 0.933 MUg/g creatinine (Cre)]
      of BPS was found in urine samples from Japan, followed by the United States
      (0.299 ng/mL, 0.304 MUg/g Cre), China (0.226 ng/mL, 0.223 MUg/g Cre), Kuwait
      (0.172 ng/mL, 0.126 MUg/g Cre), and Vietnam (0.160 ng/mL, 0.148 MUg/g Cre).
      Median concentrations of BPS in urine samples from the Asian countries were 1
      order of magnitude lower than the median concentrations reported earlier for BPA
      in the same set of samples, with the exception of samples from Japan. There were
      no significant differences in BPS concentrations between genders (male versus
      female), or among age groups (categorized as <= 19, 20-29, 30-39, 40-49, and >=
      50 years), or races (Caucasian versus Asian). The daily intake (EDI) of BPS was
      estimated on the basis of urinary concentrations using a simple pharmacokinetic
      approach. The median EDI values of BPS in Japan, China, United States, Kuwait,
      Vietnam, Malaysia, India, and Korea were 1.67, 0.339, 0.316, 0.292, 0.217, 0.122,
      0.084, and 0.023 MUg/person, respectively. This is the first study to report the
      occurrence of BPS in human urine.

PMID- 22620266
TI  - Identifying built environmental patterns using cluster analysis and GIS:
      relationships with walking, cycling and body mass index in French adults.
AB  - BACKGROUND: Socio-ecological models suggest that both individual and neighborhood
      characteristics contribute to facilitating health-enhancing behaviors such as
      physical activity. Few European studies have explored relationships between local
      built environmental characteristics, recreational walking and cycling and weight
      status in adults. The aim of this study was to identify built environmental
      patterns in a French urban context and to assess associations with recreational
      walking and cycling behaviors as performed by middle-aged adult residents.
      METHODS: We used a two-step procedure based on cluster analysis to identify built
      environmental patterns in the region surrounding Paris, France, using measures
      derived from Geographic Information Systems databases on green spaces, proximity
      facilities (destinations) and cycle paths. Individual data were obtained from
      participants in the SU.VI.MAX cohort; 1,309 participants residing in the Ile-de
      France in 2007 were included in this analysis. Associations between built
      environment patterns, leisure walking/cycling data (h/week) and measured weight
      status were assessed using multinomial logistic regression with adjustment for
      individual and neighborhood characteristics. RESULTS: Based on accessibility to
      green spaces, proximity facilities and availability of cycle paths, seven built
      environmental patterns were identified. The geographic distribution of built
      environmental patterns in the Ile-de-France showed that a pattern characterized
      by poor spatial accessibility to green spaces and proximity facilities and an
      absence of cycle paths was found only in neighborhoods in the outer suburbs,
      whereas patterns characterized by better spatial accessibility to green spaces,
      proximity facilities and cycle paths were more evenly distributed across the
      region. Compared to the reference pattern (poor accessibility to green areas and
      facilities, absence of cycle paths), subjects residing in neighborhoods
      characterized by high accessibility to green areas and local facilities and by a
      high density of cycle paths were more likely to walk/cycle, after adjustment for
      individual and neighborhood sociodemographic characteristics (OR = 2.5 95%CI 1.4
      4.6). Body mass index did not differ across patterns. CONCLUSIONS: Built
      environmental patterns were associated with walking and cycling among French
      adults. These analyses may be useful in determining urban and public health
      policies aimed at promoting a healthy lifestyle.

PMID- 22620268
TI  - PPARgamma agonist pioglitazone reverses memory impairment and biochemical changes
      in a mouse model of type 2 diabetes mellitus.
AB  - AIMS: Pioglitazone, known as a peroxisome proliferator-activated receptor gamma
      (PPARgamma) agonist, is used to treat type 2 diabetes mellitus (T2DM). T2DM has
      been associated with reduced performance on numerous domains of cognitive
      function. Here, we investigated the effects of pioglitazone on memory impairment
      in a mouse model with defects in insulin sensitivity and secretion, namely high
      fat diet (HFD) streptozotocin (STZ)-induced diabetic mice. METHODS: ICR mice were
      fed with HFD for 4 weeks and then injected with a single low dose of STZ followed
      by continued HFD feeding for an additional 4 weeks. Pioglitazone (18 mg/kg, 9
      mg/kg body weight) was orally administered for 6 weeks once daily. Y-maze test
      and Morris water maze test (MWM) were employed for testing learning and memory.
      Serum glucose, serum insulin, serum triglyceride, brain beta-amyloid peptide
      (Abeta), brain beta-site amyloid precursor protein cleaving enzyme (BACE1), brain
      nuclear factor kappaB (NF-kappaB), and brain receptor for advanced glycation end
      products (RAGE) were also tested. RESULTS: The STZ/HFD diabetic mice,
      characterized by hyperglycemia, hyperlipemia and hypoinsulinemia, performed
      poorly on Y-maze and MWM hence reflecting impairment of learning and memory
      behavior with increases of Abeta40/Abeta42, BACE1, NF-kappaB, and RAGE in brain.
      Treatment of PPARgamma agonist, pioglitazone (18 or 9 mg/kg body weight),
      significantly reversed diabetes-induced impairment of learning and memory
      behavior, which is involved in decreases of Abeta40/Abeta42 via inhibition of NF
      kappaB, BACE1 and RAGE in brain as well as attenuation of hyperglycemia,
      hyperlipemia, and hypoinsulinemia. CONCLUSIONS: It is concluded that PPARgamma
      agonist pioglitazone may be considered as potential pharmacological agents for
      the management of cognitive dysfunction in T2DM.

PMID- 22620269
TI  - Preliminary studies of neurosensory and cardiopulmonary health compromise in
      captive- bred Rhesus macaques (Macaca mulatta) suffering scoliosis.
AB  - BACKGROUND: It has been widely documented that quadrupedal animals rarely display
      natural spontaneous scoliotic rachis deviations of the spinal column. The
      objective was to determine spinal deformities developed by geriatric monkeys of
      the Macaca mulatta species, by radiographical and tomographical studies of the
      vertebral column correlating morphological changes with altered physiological
      parameters and electrical neurosensorial conductivity of somatosensory-evoked
      potentials (SEPs). MATERIALS AND METHODS: A cohort of six geriatric monkeys was
      used: three non-scoliotic subjects and three monkeys with naturally acquired true
      scoliosis. RESULTS: Radiographic and tomographic studies depicted a thoracic
      curvature displaying a left-sided thoracic vertebral rotation. The evaluation of
      physiological parameters demonstrated significant differences in the respiratory
      rate, as it was observed for the diastolic blood pressures, which showed a
      decrease in the monkeys with scoliosis compared with healthy monkeys. Regarding
      the SEPs studies, the non-parametric test for independent samples Mann-Whitney U
      test displayed a significant difference observed at the left and right thoracic
      derivative in P1; while regarding the study of upper limbs, a significant
      difference was seen at the Erb's point derivative, left afferency in P1, showing
      in all the derivatives an increase in latency in monkeys with scoliosis versus
      monkeys in the control group. CONCLUSIONS: This study has demonstrated that
      quadrupedal animals can develop true scoliosis showing an analogous way to that
      occurring in humans.

PMID- 22620271
TI  - Massive visceral pentastomiasis in a long-tailed macaque - an incidental finding.
AB  - BACKGROUND: An unusual case of visceral pentastomiasis in a male adult long
      tailed macaque imported from China is reported. METHODS: The monkey was part of a
      toxicologic study. A massive accumulation of C-shaped parasites in various
      visceral organs was found post-mortem. RESULTS: Based on the morphology of the
      nymphs, pentastomiasis was diagnosed etiopathologically. The pentastome genus and
      species was identified as Armillifer agkistrodontis by PCR and respective
      sequencing. CONCLUSION: Molecular diagnostic methods are necessary tools to
      determine the exact species involved.

PMID- 22620270
TI  - Acute traumatic spinal cord injury induces glial activation in the cynomolgus
      macaque (Macaca fascicularis).
AB  - BACKGROUND: Traumatic spinal cord injury leads to direct myelin and axonal damage
      and leads to the recruitment of inflammatory cells to site of injury. Although
      rodent models have provided the greatest insight into the genesis of traumatic
      spinal cord injury (TSCI), recent studies have attempted to develop an
      appropriate non-human primate model. METHODS: We explored TSCI in a cynomolgus
      macaque model using a balloon catheter to mimic external trauma to further
      evaluate the underlying mechanisms of acute TSCI. RESULTS: Following 1hour of
      spinal cord trauma, there were focal areas of hemorrhage and necrosis at the site
      of trauma. Additionally, there was a marked increased expression of macrophage
      related protein 8, MMP9, IBA-1, and inducible nitric oxide synthase in
      macrophages and microglia at the site of injury. CONCLUSIONS: This data indicate
      that acute TSCI in the cynomolgus macaque is an appropriate model and that the
      earliest immunohistochemical changes noted are within macrophage and microglia
      populations.

PMID- 22620272
TI  - Hematologic abnormalities associated with simian immunodeficieny virus (SIV)
      infection mimic those in HIV infection.
AB  - BACKGROUND: Studies of hematologic abnormalities in HIV-infected patients are
      confounded by a multitude of factors. A retrospective data analysis of simian
      immunodeficieny virus (SIV)-infected rhesus macaques (RM) of Indian origin was
      performed to determine the prevalence of hematologic abnormalities free of these
      confounds. METHODS: Hematologic data from RM inoculated with SIV and without
      antiviral therapy were examined pre-inoculation, and throughout infection and the
      development of AIDS. RESULTS: Anemia, thrombocytopenia, lymphopenia,
      eosinophilia, and neutropenia all increased in prevalence with SIV infection.
      Significant increases in prevalence for both neutropenia and neutrophilia were
      also detected in SIV-infected macaques. SIV-infected macaques also had lower
      lymphocyte counts and increased prevalence of lymphopenia compared with non
      infected subjects. The prevalence of eosinophilia was significantly increased
      during SIV infection. CONCLUSIONS: Concordance of hematologic abnormalities
      during SIV infection of macaques with similar changes in HIV infection of humans
      suggests that, like in HIV infection, hematologic abnormalities are major
      complications of SIV infection.

PMID- 22620273
TI  - Use of specific-pathogen-free (SPF) rhesus macaques to better model oral
      pediatric cytomegalovirus infection.
AB  - BACKGROUND: Congenital human cytomegalovirus (HCMV) infection can result in
      lifelong neurological deficits. Seronegative pregnant woman often acquire primary
      HCMV from clinically asymptomatic, but HCMV-shedding children. METHODS: Potential
      age-related differences in viral and immune parameters of primary RhCMV infection
      were examined in an oral rhesus CMV infection model in specific pathogen free
      macaques. RhCMV shedding was measured by real time PCR in plasma, saliva and
      urine. Immune parameters, including neutralizing and binding antibodies and RhCMV
      specific T cell responses, were assessed in longitudinally collected blood
      samples. RESULTS: The oral RhCMV infection model in infant SPF rhesus macaques
      demonstrated that (i) the susceptibility to oral RhCMV infection declines with
      age, and (ii) infant macaques shed RhCMV more persistently and at higher titers
      compared to adult macaques. (iii) CONCLUSIONS: The oral infant RhCMV infection
      model appears to reflect viral pathogenesis in human HCMV-infected children.
      Larger studies are needed to define immune parameters associated with better
      control of RhCMV in adult compared to young animals.

PMID- 22620274
TI  - Childbearing in adolescents aged 12-15 years in low resource countries: a
      neglected issue. New estimates from demographic and household surveys in 42
      countries.
AB  - There is strong evidence that the health risks associated with adolescent
      pregnancy are concentrated among the youngest girls (e.g. those under 16 years).
      Fertility rates in this age group have not previously been comprehensively
      estimated and published. By drawing data from 42 large, nationally representative
      household surveys in low resource countries carried out since 2003 this article
      presents estimates of age-specific birth rates for girls aged 12-15, and the
      percentage of girls who give birth at age 15 or younger. From these we estimate
      that approximately 2.5 million births occur to girls aged under 16 in low
      resource countries each year. The highest rates are found in Sub-Saharan Africa,
      where in Chad, Guinea, Mali, Mozambique, Niger and Sierra Leone more than 10% of
      girls become mothers before they are 16. Strategies to reduce these high levels
      are vital if we are to alleviate poor reproductive health.

PMID- 22620275
TI  - Immunomodulatory and antioxidant effect of Leptadenia reticulata leaf extract in
      rodents: possible modulation of cell and humoral immune response.
AB  - CONTEXT: Leptadenia reticulata Linn. (Asclpiadaceae) commonly known as "dodi," is
      an Indian medicinal plant which is known to have ethno-medical uses such as
      stimulant, tonic, immunostimulant and is one of the ingredient in ayurvedic
      formulation called as "Chawanprash," which is widely used in India to increase
      the strength of immune system. OBJECTIVE: The aim of present study is to evaluate
      immunomodulatory and antioxidant activity of ethanolic extract of L. reticulata
      L. leaves in rodents. METHODS: Haemagglutinating antibody (HA) titre,
      haematological profile (Hb, WBC, RBC), lipid peroxidation (LPO), reduced
      glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), delayed type of
      hypersensitivity (DTH) response, neutrophil adhesion test and carbon clearance
      assay were determined by in vivo experiments. RESULTS: The evaluation of
      immunomodulatory potential of L. reticulata (100, 200 mg/kg, p.o.) evoked a
      significant dose-dependent increase in antibody titre values; DTH reaction
      induced by SRBC and potentiated percentage neutrophil adhesion to nylon fibers as
      well as phagocytosis in carbon clearance assay. Also it caused significant
      increase in haematological profile, GSH, SOD, CAT activity and significantly
      decreased LPO levels in cyclophosphamide-induced immunosuppressed rats.
      CONCLUSION: The results obtained in this study indicate that L. reticulata
      possesses potential immunomodulatory and antioxidant activity and can play a
      major role in reducing the risk to develop immunodeficiency disorders.

PMID- 22620276
TI  - Scientific gear as a vector for non-native species at deep-sea hydrothermal
      vents.
AB  - The fauna of deep-sea hydrothermal vents are among the most isolated and
      inaccessible biological communities on Earth. Most vent sites can only be visited
      by subsea vehicles, which can and do move freely among these communities.
      Researchers assume individuals of the regionally homogeneous vent fauna are
      killed by the change in hydrostatic pressure the animals experience when the
      subsea vehicles, which collected them, rise to the surface. After an Alvin dive,
      we found 38 apparently healthy individuals of a vent limpet in a sample from a
      hydrothermally inactive area. Prompted by our identification of these specimens
      as Lepetodrilus gordensis, a species restricted to vents 635 km to the south of
      our dive site, we tested whether they were from a novel population or were
      contaminants from the dive made 36 h earlier. The 16S gene sequences, morphology,
      sex ratio, bacterial colonies, and stable isotopes uniformly indicated the
      specimens came from the previous dive. We cleaned the sampler, but assumed
      pressure changes would kill any organisms we did not remove and that the faunas
      of the 2 areas were nearly identical and disease-free. Our failure to completely
      clean the gear on the subsea vehicle meant we could have introduced the species
      and any diseases it carried to a novel location. Our findings suggest that the
      nearly inaccessible biological communities at deep-sea vents may be vulnerable to
      anthropogenic alteration, despite their extreme physical conditions.

PMID- 22620277
TI  - Neurophysiological testing to assess penile sensory nerve damage after radical
      prostatectomy.
AB  - INTRODUCTION: Radical prostatectomy (RP) can lead to erectile dysfunction due to
      surgical injury of the cavernous nerves. However, there is no simple, objective
      test to evaluate cavernous nerve damage caused by RP in clinical practice. AIM:
      To assess the value of the measurement of penile thermal and vibratory sensory
      thresholds to reflect cavernous nerve damage caused by RP. METHODS: We included
      42 consecutive patients who underwent RP with cavernous nerve sparing
      (laparoscopic approach, N = 12) or without cavernous nerve sparing (laparoscopic,
      N = 13; retropubic, N = 11; or transperineal, N = 6). Penile thermal (warm and
      cold) and vibratory sensory thresholds were measured twice, together with the
      Erectile Dysfunction Symptom Score (EDSS), 1 month before and 2 months after RP.
      MAIN OUTCOME MEASURES: Penile sensory thresholds for warm, cold, and vibration
      sensations. RESULTS: Penile sensory thresholds for warm (P < 0.0001) and cold (P
      < 0.0001) sensations significantly increased after non-nerve-sparing RP, but not
      after nerve-sparing RP. Vibration threshold only increased after transperineal
      non-nerve-sparing RP (P = 0.031). EDSS values were significantly increased in all
      groups of patients 2 months after surgery. CONCLUSIONS: Sensory nerve fibers
      carrying penile skin sensations travel with the cavernous nerves in the pelvis.
      Therefore, testing these sensations may help to evaluate the extent of cavernous
      nerve damage caused by RP. In this series, post-operative changes in penile
      sensory thresholds differed with the surgical technique of RP, as the cavernous
      nerves were preserved or not. The present results support the value of
      quantitative penile sensory threshold measurement to indicate RP-induced
      cavernous nerve injury.

PMID- 22620278
TI  - Service suspension for mental disorders in armed forces draftees in the Penghu
      area.
AB  - BACKGROUND: It is important to monitor draftees for mental disorders before or at
      an early stage of military service. The aim of this study was to characterize the
      draftees who were suspended from service for mental disorders among draftees in a
      high readiness military zone in the Taiwan Strait. METHOD: A total of 152
      draftees consulted the outpatient service of the Department of Psychiatry at
      Penghu branch, Tri-Service General Hospital in Taiwan during the period between
      August 2004 and July 2008, and whose severity of mental disorder fit the criteria
      for service suspension were recruited as the study group (SG). Draftees who had
      adjusted normally were the control group (CG). RESULTS: The major causes for
      suspension were major depressive disorders and personality disorders. In the
      study group, the number of draftees seeking psychiatric outpatient treatment
      increased from 49.3% before service to 100% during service. In addition, higher
      rates of suicidal ideation, suicide plans, attempted suicide, and homicidal
      ideation were found in the study group than in the control group. The percentages
      of draftees who were unwilling to serve and absent without official leave (AWOL)
      during military service in Penghu were also significantly higher in the study
      group than in the control group. CONCLUSIONS: Based on the characteristics of the
      draftees who were suspended from service for mental disorders, psychological
      factors such as suicidal ideation, suicide attempts and adjustment disorders
      should be surveyed and monitored before the draft and at an early stage of
      military service.

PMID- 22620279
TI  - Quantifying instantaneous performance in alpine ski racing.
AB  - Alpine ski racing is a popular sport in many countries and a lot of research has
      gone into optimising athlete performance. Two factors influence athlete
      performance in a ski race: speed and the chosen path between the gates. However,
      to date there is no objective, quantitative method to determine instantaneous
      skiing performance that takes both of these factors into account. The purpose of
      this short communication was to define a variable quantifying instantaneous
      skiing performance and to study how this variable depended on the skiers' speed
      and on their chosen path. Instantaneous skiing performance was defined as time
      loss per elevation difference dt/dz, which depends on the skier's speed v(z), and
      the distance travelled per elevation difference ds/dz. Using kinematic data
      collected in an earlier study, it was evaluated how these variables can be used
      to assess the individual performance of six ski racers in two slalom turns. The
      performance analysis conducted in this study might be a useful tool not only for
      athletes and coaches preparing for competition, but also for sports scientists
      investigating skiing techniques or engineers developing and testing skiing
      equipment.

PMID- 22620280
TI  - Traditional serrated adenoma of the sigmoid colon with osseous metaplasia: a case
      report.
AB  - INTRODUCTION: Osseous metaplasia in the gastrointestinal tract is a rare
      phenomenon. CASE PRESENTATION: We present the case of a 62-year-old Hispanic man
      with two colonic polypoid lesions, one of which, upon resection and
      histopathological examination, was found to be a traditional serrated adenoma
      with a focus of stromal osseous metaplasia. CONCLUSIONS: Our patient's case is
      the third report of stromal osseous metaplasia in a traditional serrated adenoma
      of the sigmoid colon.

PMID- 22620281
TI  - Differential effects of androgens on coronary blood flow regulation and
      arteriolar diameter in intact and castrated swine.
AB  - BACKGROUND: Low endogenous testosterone levels have been shown to be a risk
      factor for the development of cardiovascular disease and cardiovascular benefits
      associated with testosterone replacement therapy are being advocated; however,
      the effects of endogenous testosterone levels on acute coronary vasomotor
      responses to androgen administration are not clear. The objective of this study
      was to compare the effects of acute androgen administration on in vivo coronary
      conductance and in vitro coronary microvascular diameter in intact and castrated
      male swine. METHODS: Pigs received intracoronary infusions of physiologic levels
      (1-100 nM) of testosterone, the metabolite 5alpha-dihydrotestosterone, and the
      epimer epitestosterone while left anterior descending coronary blood flow and
      mean arterial pressure were continuously monitored. Following sacrifice, coronary
      arterioles were isolated, cannulated, and exposed to physiologic concentrations
      (1-100 nM) of testosterone, 5alpha-dihydrotestosterone, and epitestosterone. To
      evaluate effects of the androgen receptor on acute androgen dilation responses,
      real-time PCR and immunohistochemistry for androgen receptor were performed on
      conduit and resistance coronary vessels. RESULTS: In vivo, testosterone and
      5alpha-dihydrotestosterone produced greater increases in coronary conductance in
      the intact compared to the castrated males. In vitro, percent maximal dilation of
      microvessels was similar between intact and castrated males for testosterone and
      5alpha-dihydrotestosterone. In both studies epitestosterone produced significant
      increases in conductance and microvessel diameter from baseline in the intact
      males. Androgen receptor mRNA expression and immunohistochemical staining were
      similar in intact and castrated males. CONCLUSIONS: Acute coronary vascular
      responses to exogenous androgen administration are increased by endogenous
      testosterone, an effect unrelated to changes in androgen receptor expression.

PMID- 22620282
TI  - Wound debridement potential of glycosidases of the wound-healing maggot, Lucilia
      sericata.
AB  - The wound-healing maggot, Lucilia sericata Meigen (Diptera: Calliphoridae),
      degrades extracellular matrix components by releasing enzymes. The purpose of
      this study was to investigate the glycosylation profiles of wound slough/eschar
      from chronic venous leg ulcers and the complementary presence of glycosidase
      activities in first-instar excretions/secretions (ES1) and to define their
      specificities. The predominant carbohydrate moieties present in wound
      slough/eschar were determined by probing one-dimensional Western blots with
      conjugated lectins of known specificities. The presence of specific glycosidase
      activities in ES1 was determined using chromogenic and fluorogenic substrates.
      The removal of carbohydrate moieties from slough/eschar proteins by glycosidases
      in ES1 was determined by two-dimensional electrophoresis and Emerald 300
      glycoprotein staining. alpha-D-glucosyl, alpha-D-mannosyl and N-acetylglucosamine
      residues were detected on slough/eschar-derived proteins. Furthermore, it was
      demonstrated that the treatment of slough/eschar with ES1 significantly reduced
      uptake of the carbohydrate-specific stain. Subsequently, alpha-D-glucosidase,
      alpha-D-mannosidase and N-acetylglucosaminidase activities were identified in
      ES1. Specific chromogenic and fluorogenic substrates and gel filtration
      chromatography showed that these activities result from distinct enzymes. These
      activities were mirrored in the removal of alpha-D-glucosyl, alpha-D-mannosyl and
      N-acetylglucosamine residues from proteins of slough/eschar from maggot-treated
      wounds. These data suggest that maggot glycosidases remove sugars from
      slough/eschar proteins. This may contribute to debridement, which is ultimately
      accomplished by a suite of biochemically distinct enzymes present in ES1.

PMID- 22620283
TI  - The medical student as a patient: attitudes towards involvement in the quality
      and safety of health care.
AB  - BACKGROUND: In recent years, factors that affect patients' willingness and
      ability to participate in safety-relevant behaviours have been investigated.
      However, how trained healthcare professionals or medical students would feel
      participating in safety-relevant behaviours as a patient in hospital remains
      largely unexplored. OBJECTIVES: To investigate medical students' willingness to
      participate in behaviours related to the quality and safety of their health care.
      DESIGN: A cross-sectional exploratory study using a survey that addressed
      willingness to participate in different behaviours recommended by current patient
      safety initiatives. Three types of interactional behaviours (asking factual or
      challenging questions, notifying doctors or nurses of errors/problems) and three
      non-interactional behaviours (choosing a hospital based on the safety record,
      bringing medicines and a list of allergies into hospital, and reporting an error
      to a national reporting system) were assessed. PARTICIPANTS: One hundred and
      seventy-nine medical students from an inner city London teaching hospital
      participated in the study. FINDINGS: Students' willingness to participate was
      affected (P < 0.05) by the action required by the patient and (for interactional
      behaviours) whether the patient was engaging in the specific action with a doctor
      or nurse. Students were least willing to ask 'challenging' questions to doctors
      and nurses and to report errors to a national reporting system. Doctors' and
      nurses' encouragement appeared to increase self-reported willingness to
      participate in behaviours where baseline willingness was low. CONCLUSION: Similar
      to research on lay patient populations; medical students do not view involvement
      in safety-related behaviours equally. Interventions should be tailored at
      encouraging students to participate in behaviours they are less inclined to take
      on an active role in. Future research is required to examine students'
      motivations for participation in this important but heavily under-researched
      area.

PMID- 22620284
TI  - Workers with health problems: three perspectives on functioning at work.
AB  - PURPOSE: Our aims were (i) to explore why it is that one worker with a health
      problem is able to stay at work while the other is not, (ii) to identify signals
      for decreased functioning at work, and (iii) to explore if and how this can be
      measured. METHOD: We conducted three focus groups: with workers with a health
      problem, occupational physicians, and human resources managers/supervisors.
      RESULTS: Individual differences in coping strategies, motivation, believes,
      attitudes, and values were mentioned. All three groups reported that the
      supervisor is the key figure in the functioning at work of workers with health
      problems. The supervisor can facilitate the work accommodation of workers and
      help optimizing functioning at work. The identified signals might contribute to
      the development of an instrument. Conditions for use were suggested, i.e. a
      "safe" setting. CONCLUSIONS: This focus group study provided insight in why it is
      that one worker is able to stay at work while the other is not, according to the
      opinions of three different groups. Although all three groups reported that the
      supervisor is the key figure in the functioning at work of workers with health
      problems, there are differences between how the three stakeholders perceive the
      situation.

PMID- 22620285
TI  - Sleep apnea as a comorbidity in obese psoriasis patients: a cross-sectional
      study. Do psoriasis characteristics and metabolic parameters play a role?
AB  - BACKGROUND: Psoriasis is associated with a variety of comorbidities such as
      obesity and cardiovascular disease. OBJECTIVE: In a cross-sectional study, we
      explored whether obstructive sleep apnea and hypopnea syndrome (OSAHS) is
      associated with psoriasis characteristics and metabolic parameters. METHODS:
      Thirty-five patients with chronic plaque psoriasis underwent a nocturnal
      polysomnography study and were analysed for Apnoea-Hypopnoea Index to assess
      OSAHS severity and Framigham score to predict the absolute risk of coronary
      artery disease at 10 years. The association of OSAHS with psoriasis was examined
      according to psoriasis characteristics (PASI and DLQI scores, disease duration
      and previous use of systemic treatments), metabolic parameters (Body Mass Index -
      BMI, waist to hip ratio - WHR, lipid profile) and other comorbidities (obesity,
      hypertension, arthritis and cardiovascular disease). RESULTS: There was no
      correlation between psoriasis characteristics and OSAHS. Psoriasis patients with
      OSAHS presented more frequent snoring and lower sleep quality compared with those
      without OSAHS. In univariate analyses, OSAHS was associated with increased BMI
      and hypertension in psoriasis patients. In multivariable logistic regression
      models, there was statistically significant evidence that only BMI and
      hypertension were associated with increased risk of OSAHS, adjusting for
      psoriasis characteristics, age and gender. Presence of metabolic syndrome, WHR,
      and smoking were not significant risk factors for OSAHS. In subgroup analyses,
      OSAHS correlated with duration of psoriasis (>8 years) in women (P = 0.021) and
      with Framigham score in men (P = 0.035). CONCLUSION: OSAHS may be a comorbidity
      in obese psoriasis patients with hypertension. Treatment with continuous positive
      airway pressure and weight loss interventions should be initiated.

PMID- 22620286
TI  - SITC 26th annual meeting--summary.
AB  - The 26th annual meeting of the Society for Immunotherapy of Cancer took place in
      Bethesda on November 4 to 6, 2011 and was organized by Charles G. Drake (Johns
      Hopkins University) Dolores J. Schendel (Helmholtz Zentrum Muenchen - German
      Research Center for Environmental Health Institute of Molecular Immunology),
      Jeffrey Schlom (National Cancer Institute, National Institutes of Health), and
      Jedd D. Wolchok (Memorial Sloan-Kettering Cancer Center). It was an event marked
      by a number of extraordinary circumstances: it attracted a record attendance of
      805 participants from 24 different countries. The gathering came in the wake of
      great as well as very sad news for the tumor immunology community. Good news
      included the approval of anti-CTLA-4 as a therapy for metastatic melanoma in
      April and the announcement in early October of the Nobel Prize in Physiology and
      Medicine awarded to pioneering studies in the field of immunology. Indeed, one
      part of the prize went to Dr. Bruce Beutler, Scripps Research Institute, La
      Jolla, USA and Dr. Jules Hoffman, Institute for Molecular Cell Biology,
      Strasbourg, France, for their discoveries in innate immunity and the other part
      to Dr. Ralph Steinman, The Rockfeller University, New York, for his discovery of
      dendritic cells. Sad news was the losses of two giants in the field. Jurg Tschopp
      of the University of Lausanne in March and Ralph Steinman, who passed away just
      three days before his Nobel Prize announcement. The loss of these two charismatic
      scientific leaders was particularly sad for the Annual Meeting as both J. Tschopp
      and R. Steinman were confirmed speakers at this meeting: the former to deliver
      the keynote lecture and the latter as recipient of the Richard V. Smalley prize.

PMID- 22620288
TI  - Hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome in a 26-year
      old woman with cystic fibrosis: a case report.
AB  - INTRODUCTION: The microangiopathic hemolysis, elevated liver enzymes, and low
      platelet (HELLP) syndrome is a rare and potentially fatal complication of
      pregnancy. Here, to the best of our knowledge, we describe only the second
      reported case of this syndrome in a woman with cystic fibrosis. CASE
      PRESENTATION: This report describes the case of a 26-year-old woman of Caucasian
      ethnicity with mild cystic fibrosis bronchiectasis who ultimately manifested the
      triad of microangiopathic hemolysis, elevated liver enzymes, and low platelet
      count in the third trimester of pregnancy. Her baby was delivered successfully
      after a semi-elective caesarean section. CONCLUSIONS: Pregnancies in patients
      with cystic fibrosis are associated with an increased rate of complications. This
      case is of importance as it describes only for the second time the successful
      delivery of a baby in a women with cystic fibrosis, in a pregnancy also
      threatened by the microangiopathic hemolysis, elevated liver enzymes, and low
      platelet syndrome. This case will be of special interest to obstetricians,
      pediatricians, and medical, nursing and allied health staff involved in the
      delivery of cystic fibrosis care.

PMID- 22620287
TI  - Sexually dimorphic effect of aging on skeletal muscle protein synthesis.
AB  - BACKGROUND: Although there appear to be no differences in muscle protein turnover
      in young and middle aged men and women, we have reported significant differences
      in the rate of muscle protein synthesis between older adult men and women. This
      suggests that aging may affect muscle protein turnover differently in men and
      women. METHODS: We measured the skeletal muscle protein fractional synthesis rate
      (FSR) by using stable isotope-labeled tracer methods during basal postabsorptive
      conditions and during a hyperaminoacidemic-hyperinsulinemic-euglycemic clamp in
      eight young men (25-45 y), ten young women (25-45 y), ten old men (65-85 y) and
      ten old women (65-85 y). RESULTS: The basal muscle protein FSR was not different
      in young and old men (0.040 +/- 0.004 and 0.043 +/- 0.005%.h-1, respectively) and
      combined insulin, glucose and amino acid infusion significantly increased the
      muscle protein FSR both in young (to 0.063 +/- 0.006%.h-1) and old (to 0.051 +/-
      0.008%.h-1) men but the increase (0.023 +/- 0.004 vs. 0.009 +/- 0.004%.h-1,
      respectively) was ~60% less in the old men (P = 0.03). In contrast, the basal
      muscle protein FSR was ~30% greater in old than young women (0.060 +/- 0.003 vs.
      0.046 +/- 0.004%.h-1, respectively; P < 0.05) and combined insulin, glucose and
      amino acid infusion significantly increased the muscle protein FSR in young (P <
      0.01) but not in old women (P = 0.10) so that the FSR was not different between
      young and old women during the clamp (0.074 +/- 0.006%.h-1 vs. 0.072 +/- 0.006%.h
      1, respectively). CONCLUSIONS: There is sexual dimorphism in the age-related
      changes in muscle protein synthesis and thus the metabolic processes responsible
      for the age-related decline in muscle mass.

PMID- 22620289
TI  - Carbamazepine treatment of bipolar disorder: a retrospective evaluation of
      naturalistic long-term outcomes.
AB  - BACKGROUND: Carbamazepine (CBZ) has been used in the treatment of bipolar
      disorder, both in acute mania and maintenance therapy, since the early 1970s.
      Here, we report a follow-up study of CBZ-treated bipolar patients in the Taipei
      City Psychiatric Centre. METHODS: Bipolar patients diagnosed according to the DSM
      IV system and treated with CBZ at the Taipei City Psychiatric Centre had their
      charts reviewed to evaluate the efficacy and side effects of this medication
      during an average follow-up period of 10 years. RESULTS: A total of 129 bipolar
      patients (45 males, mean age: 45.7 +/- 10.9 year) were included in the analysis
      of CBZ efficacy used alone (n = 63) or as an add-on after lithium (n = 50) or
      valproic acid (n = 11), or the both of them (n = 5). The mean age of disease
      onset was 24.6 +/- 9.5 years. The mean duration of CBZ use was 10.4 +/- 5.2 year.
      The mean dose used was 571.3 +/- 212.6 mg/day with a mean plasma level of 7.8 +/-
      5.9 MUg/mL. Mean body weight increased from 62.0 +/- 13.4 kg to 66.7 +/- 13.1 kg
      during treatment. The frequencies of admission per year before and after CBZ
      treatment were 0.33 +/- 0.46 and 0.14 +/- 0.30, respectively. The most common
      side effects targeted the central nervous system (24%), including dizziness,
      ataxia and cognitive impairment. Other common side effects were gastrointestinal
      disturbances (3.6%), tremor (3.6%), skin rash (2.9%), and blurred vision (2.9%).
      Eighty-eight patients (68.2%) were taking antipsychotics concomitantly. Ninety
      six patients (74.4%) needed to use benzodiazepines concomitantly. Sixty-three
      (48.8%) patients had zero episodes in a 10-year follow-up period, compared to all
      patients having episodes prior to treatment. Using variable analysis, we found
      better response to CBZ in males than in females. CONCLUSIONS: CBZ is efficacious
      in the maintenance treatment of bipolar disorder in naturalistic clinical
      practice, either as monotherapy or in combination with other medications. CBZ is
      well tolerated by most patients in this patient group.

PMID- 22620469
TI  - Comparison of ultrasound echo-tracking technology and pulse wave velocity for
      measuring carotid elasticity among hemodialysis patients.
AB  - This study aims to investigate the correlation between carotid elasticity in
      hemodialysis patients as evaluated by ultrasound echo-tracking technology and
      aortic pulse wave velocity. A total of 103 patients with end-stage renal disease
      who underwent stable hemodialysis were enrolled. An ultrasonic echo-tracking
      method was used to evaluate the elastic modulus and the stiffness index (beta),
      which were compared with pulse wave velocity (PWV). Blood glucose, blood lipids,
      and serum creatinine were also tested. These indices were analyzed to determine
      the independent factor for arterial elasticity. The carotid elastic modulus and
      beta were in good correlation with PWV among hemodialysis patients (P = 0.000).
      Diabetes and age are independent risk factors for arterial elasticity among
      hemodialysis patients. Ultrasound echo-tracking technology is a sensitive and
      accurate method for evaluating arterial elasticity and is a good alternative to
      traditional PWV.

PMID- 22620470
TI  - Superhydrophobic surfaces as smart platforms for the analysis of diluted
      biological solutions.
AB  - The aim of this paper is to expound on the rational design, fabrication and
      development of superhydrophobic surfaces (SHSs) for the manipulation and analysis
      of diluted biological solutions. SHSs typically feature a periodic array or
      pattern of micropillars; here, those pillars were modified to incorporate on the
      head, at the smallest scales, silver nanoparticles aggregates. These metal
      nanoclusters guarantee superior optical properties and especially SERS (surface
      enhanced Raman scattering) effects, whereby a molecule, adsorbed on the surface,
      would reveal an increased spectroscopy signal. On account of their two scale
      hybrid nature, these systems are capable of multiple functions which are (i) to
      concentrate a solution, (ii) to vehicle the analytes of interest to the active
      areas of the substrate and, therefore, (iii) to measure the analytes with
      exceptional sensitivity and very low detection limits. Forasmuch, combining
      different technologies, these devices would augment the performance of
      conventional SERS substrates and would offer the possibility of revealing a
      single molecule. In this work, similar SHSs were used to detect Rhodamine
      molecules in the fairly low atto molar range. The major application of this novel
      family of devices would be the early detection of tumors or other important
      pathologies, with incredible advances in medicine. 

PMID- 22620471
TI  - Rural residents need research.

PMID- 22620472
TI  - Northern Territory Emergency Response: criticism, support and redesign.
AB  - The recent Federal Government Report and Media release, Stronger Futures in the
      Northern Territory: Report on Consultations and its claim of 'widespread
      Indigenous Support' has brought the topic of the Northern Territory Emergency
      Response (the Intervention) back into the public mind. This article provides a
      synthesis of four years of debate around the Northern Territory Emergency
      Response, at a time when the program is nearing the end of its time frame. It
      outlines the main arguments supporting the Intervention, the central criticisms
      and the government's response to these evaluations, with the aim of providing a
      primer or summary for health professionals to the discussion around this
      important public issue.

PMID- 22620473
TI  - Food scarcity, not economic constraint limits consumption in a rural Aboriginal
      community.
AB  - OBJECTIVE: To determine whether food scarcity or economic constraint is more
      strongly associated with purchasing patterns in a rural Aboriginal community.
      DESIGN: Store receipts were collected to determine money spent in the community
      shop across a four-month period from January to April 2006. Variability in
      expenditures is then studied using measures of food scarcity (days since shop
      loading) and economic constraint (days since payday). SETTING: Parnngurr
      Outstation in the Western Desert of Australia. MAIN OUTCOME MEASURES: Daily gross
      and per-household gross expenditures at the community shop. RESULTS:   There is a
      significant association between food scarcity and money spent in the shop (
      42.89, confidence interval -62.62 to -23.18, P < 0.001). There is no association
      between economic constraint and money spent in the shop. CONCLUSION: In rural and
      remote communities, reliable access to food is critical to food security.
      Circumstantial constraints such as seasonal flooding and political insecurity can
      augment food access problems and put Aboriginal people at risk of malnutrition
      and other dietary harms.

PMID- 22620474
TI  - The benefits of a tailor-made pilot primary health-care course for Indigenous
      high school students in remote Queensland.
AB  - OBJECTIVE: This study highlights the benefits of a tailor-made course for an
      Indigenous high school in a remote North Queensland community. DESIGN:
      Qualitative research study using a Grounded Theory approach to allow thematic
      analysis of participant's responses to a researcher-administered, pre-defined,
      semistructured questionnaire. SETTING: Remote community college in Abergowrie,
      North Queensland. PARTICIPANTS: Four male high school students and eight key
      stakeholders were interviewed over the telephone (n = 12). RESULTS: Thematic
      analyses of the feedback from students and stakeholders showed a variety of
      benefits from the course for Indigenous students: increased knowledge of health
      issues, greater awareness and interest in health career pathways, increased
      pride, self-esteem and self-confidence, positive role-modelling and leadership
      behaviour in the students, and hope for future career development. Weaknesses
      identified were mainly associated with a lack of resources and support for the
      course. CONCLUSIONS: This study demonstrates that a tailor-made primary health
      care education course can create opportunities for Indigenous people to pursue
      health careers, promote health knowledge and leadership skills, inspire pride and
      self-esteem, and strengthen links within the community.

PMID- 22620475
TI  - In the wake of the 2009 Gippsland fires: young adults' perceptions of post
      disaster social supports.
AB  - OBJECTIVE: To explore young (18-27 years) rural adults' experience of both formal
      and informal social support networks post-bushfire. To inform delivery of social
      support services for young adults post-bushfire. DESIGN: Qualitative: semi
      structured, face-to-face interviews with transcripts analysed using thematic
      content analysis. SETTING: Gippsland 2009 flame-impacted regions: Boolarra and
      Central Gippsland Black Saturday fire complexes. PARTICIPANTS: Ten bushfire
      impacted young adults (18-27 years): six female and four male. RESULTS: The
      central theme was the importance of acknowledgement and validation of
      participants' experience as autonomous individuals. Participants' experience of
      social supports and networks as either helpful or unhelpful depended on the
      degree to which the supports delivered enhanced sense of acknowledgement,
      entitlement, affiliation, informational links, engagement in the recovery process
      and amelioration of displacement in relation to family, friends, community and
      environment. CONCLUSION: Participants believed that how an individual, community
      or service provider framed loss had a significant impact on entitlement and how
      needs were met. Importantly, how society, policy and service providers framed
      young adults as either adult or adolescent impacts on how their needs were met.
      This study highlights the need to resituate how loss is viewed and the need for
      policy and service providers to address the existing nomenclature mismatch and
      framing of loss so that young adults are not excluded from supports essential to
      recovery.

PMID- 22620476
TI  - Mental health and well-being in resident mine workers: out of the fly-in fly-out
      box.
AB  - OBJECTIVE: To explore psychosocial issues perceived to impact the mental health
      and well-being of resident (non-fly-in fly-out) mine workers at a local mine in
      regional Queensland. DESIGN: A descriptive qualitative study using semistructured
      interviews. SETTING: The research was conducted on-site at an open-cut coal mine
      in regional Queensland. PARTICIPANTS: Ten miners (nine men) currently employed in
      workshop, production or supervisory roles. MAIN OUTCOME MEASURES: Self-reported
      issues affecting psychological well-being. RESULTS: Participants' occupation and
      the surrounding context appeared to have both positive and negative influences on
      their well-being. Overall findings could be grouped into four key themes: (i) the
      importance of relationships; (ii) the impact of lifestyle; (iii) work
      characteristics; and (iv) mental health attitudes. While not without strains on
      mental health, in general, participants reported that their current situation was
      superior to their previous mining jobs. This was attributed to close
      relationships among locally recruited workers, respect for management practices
      and rosters that allowed adequate sleep recovery and family time between shifts.
      CONCLUSIONS: This study is the first to examine mental health and well-being in
      non-fly-in fly-out mining populations. It suggests that while some issues appear
      inherent in the mining occupation, personal and organisational support can help
      workers have a more positive workplace experience. Further work looking at more
      extensive comparisons over various mining contexts will greatly assist in the
      development of programs and support structures for rural and regional mine
      workers.

PMID- 22620477
TI  - Cardiovascular risk factors and psychological distress in Australian farming
      communities.
AB  - OBJECTIVE: To examine the prevalence of cardiovascular disease (CVD) risk
      factors, psychological distress and associations between physical and mental
      health parameters within a cohort of the Australian farming community. DESIGN:
      Cross-sectional descriptive study. SETTING: Farming communities across Australia.
      PARTICIPANTS: Data of men (n = 957) and women (n = 835) farmers from 97 locations
      across Australia were stratified into categories based on National Cholesterol
      Education Program guidelines. MAIN OUTCOME MEASURE(S):   Prevalence of and
      interrelationship between overweight, obesity, dyslipidaemia, hypertension,
      diabetes risk and psychological distress. RESULTS: There was a higher prevalence
      of overweight (42.5%, 95% confidence interval (CI), 34.2-50.8), obesity (21.8%,
      95% CI, 18.3-25.3), abdominal adiposity (38.4% 95% CI, 24.5-52.5), hypertension
      (54.0%, 95% CI, 34.4-73.5) and diabetes risk (25.3%, 95% CI, 17.7-36.7) in the
      farming cohort compared with national data. There was also a positive significant
      association between the prevalence of psychological distress and obesity,
      abdominal adiposity, body fat percentage and metabolic syndrome in older (age >=
      50 years) participants. CONCLUSIONS: This study group of farming men and women
      exhibited an increased prevalence of CVD risk factors and co-morbidities. The
      findings indicate a positive association between psychological distress and risk
      for developing CVD, particularly in the older farmers. If the younger cohort were
      to maintain elevated rates of psychological distress, then it is foreseeable that
      the next generation of farmers could experience poorer physical health than their
      predecessors.

PMID- 22620478
TI  - Issues with medication supply and management in a rural community in Queensland.
AB  - OBJECTIVE: To identify the key issues reported by rural health-care providers in
      their provision of medication supply and related cognitive services, and in order
      to advise health workforce and role development and thus improve the quality use
      of medicines in rural communities. DESIGN: Exploratory semistructured interview
      research. SETTING: A rural community comprising four towns in a rural health
      service district in Queensland, Australia. PARTICIPANTS:   Forty-nine health-care
      providers (medical practitioners, pharmacists, nurses and others) with medication
      related roles who serviced the study community, identified through databases and
      local contacts. MAIN OUTCOME MEASURES: Medication-related roles undertaken by the
      health-care providers, focusing on medication supply and cognitive services;
      challenges in undertaking these roles. RESULTS: Medical and nursing providers
      reported challenges in ensuring continuity in supply of medications due to their
      existing medical workload demands. Local pharmacists were largely involved in
      medication supply, with limited capacity for extended cognitive roles.
      Participants identified a lack of support for their medication roles and the
      potential value of clinically focused pharmacists in medication management
      services. CONCLUSIONS: Medication supply may become more efficient with extended
      roles for certain health-care providers. The need for cognitive medication
      management services suggests potential for clinical pharmacists' role development
      in rural areas.

PMID- 22620479
TI  - Trade-off between local access and safety considerations in childbirth: rural
      Tasmanian women's perspectives.
AB  - OBJECTIVES: This study investigates: (i) Tasmanian rural women's preferences for
      different models of intrapartum care; (ii) their preferences for travel time to
      safe delivery; and (iii) factors which influence these preferences. DESIGN: Mixed
      methods study using a survey questionnaire and semistructured interviews was
      adopted. A questionnaire explored women's preferences for different models of
      care and preferred travel time. Interviews were conducted to validate the survey
      results and provide insightful information on their preferences on the models of
      care. Women who have had rural childbirth experiences from six Tasmanian rural
      communities were invited to participate in the study. RESULTS: Two hundred and
      ten women completed the questionnaire with a response rate of 35%. Twenty-two
      follow-up interviews were conducted. The survey found that women preferred to
      give birth in a hospital setting to homebirth despite having to travel for two
      hours. Midwifery-led care with one hour travel time was the second preferred
      model of care. Women were willing to travel to access the regional hospital but
      within limit. Their preferences suggest that women have to trade-off between
      local access and safety considerations. The interviews validate the survey
      results. Three main themes emerged from the interview data namely (i) safety;
      (ii) distance from hospital; and (iii) type of delivery. Their preferences were
      associated with their maternal care experiences in the past. CONCLUSION: In order
      to achieve the maternity services that are woman centred and respond to the needs
      and preferences of women, the service design and provision should take into
      account these women's preferences.

PMID- 22620480
TI  - Who brings dengue into North Queensland? A descriptive, exploratory study.
AB  - OBJECTIVE: To describe the demographics, patterns of assessment and treatment of
      people visiting a regional emergency department with potential diagnoses of
      malaria or dengue fever. DESIGN: To identify potential dengue fever cases, we
      used an indicator of recent overseas travel and fever that is a request for
      malaria testing. A chart audit of 301 medical records of people between 2008 and
      2010 was conducted to describe patient characteristics, diagnostic tests
      performed and treatment. SETTING: A regional hospital located in the wet tropics.
      RESULTS: Malaria testing was most often performed on Australian citizens (64.1%),
      medical evacuees (20.3%) and tourists (18.6%). Overall, 49.8% of patients tested
      for malaria did not also have a dengue test, despite being indicated in 54% of
      this group. People tested for malaria usually lived in a residential house or
      unit (69.7%). Only 9% were staying in hotels and hostels. Oceania was the most
      commonly visited region in the two weeks prior to presentation. Malaria was
      diagnosed in 17.3% and dengue fever in 12% of patients tested. Patients with
      dengue fever were more likely than patients with malaria to self-refer to
      hospital, be staying in commercial accommodation and to have recently travelled
      to Southeast Asia. CONCLUSION: Both dengue fever and malaria occur predominantly
      in residents who reside in non-commercial accommodation. Efforts to identify
      imported dengue fever cases should focus on both tourists and local residents
      returning from overseas countries.

PMID- 22620481
TI  - Celebrating another decade of progress in rural health: what is the current state
      of play?
AB  - The Australian Journal of Rural Health is currently celebrating its 20th
      anniversary. Following a review of the first decade of rural health published by
      the authors in 2002, this article outlines and reviews the range of policies that
      have impacted upon rural health in Australia since then. During the past decade
      there has been a raft of new policies and programs designed to bring about
      improved rural health outcomes, and some progress has been made. However, a
      number of significant barriers to overcoming the rural-urban health differential
      remain. Special consideration will continue to be needed to rural affairs
      generally and to health system reform and rural health in particular.

PMID- 22620483
TI  - Holistic health care in rural India.

PMID- 22620484
TI  - Interpreting transition from adolescence to adulthood in patients on dialysis who
      have end-stage renal disease.
AB  - BACKGROUND: Patients with End-Stage Renal Disease (ESRD) undergo renal
      replacement therapies such as haemodialysis, and usually have to deal with a
      lifetime of treatment. If an individual has ESRD at a young age, eventually the
      individual experiences a stage of transition from adolescence to adulthood.
      METHODS: Interpretive phenomenology was used to uncover the meaning of transition
      from adolescence to adulthood. Six patients on haemodialysis between the ages of
      17 to 22 years agreed to participate in the study. Multiple sources of data were
      utilised: semi-structured interviews, video recordings, diaries and field notes.
      Using Ricoeur's theory of interpretation, the data were analysed. RESULTS: Three
      general themes were found: Living a Shorter Life; Dependence and Independence;
      and Struggle of Being Normal Amidst Difference. CONCLUSION: Transition to
      Adulthood among patients with ESRD is like a pendulum continuously moving in a
      back and forth motion. The "World-in-Between" is a constant search of self within
      two ends of characteristics: of holding on and giving up; expression and non
      expression of self.

PMID- 22620485
TI  - The FKBP-rapamycin binding domain of human TOR undergoes strong conformational
      changes in the presence of membrane mimetics with and without the regulator
      phosphatidic acid.
AB  - The Ser/Thr kinase target of rapamycin (TOR) is a central controller of cellular
      growth and metabolism. Misregulation of TOR signaling is involved in metabolic
      and neurological disorders and tumor formation. TOR can be inhibited by
      association of a complex of rapamycin and FKBP12 to the FKBP12-rapamycin binding
      (FRB) domain. This domain was further proposed to interact with phosphatidic acid
      (PA), a lipid second messenger present in cellular membranes. Because mammalian
      TOR has been localized at various cellular membranes and in the nucleus, the
      output of TOR signaling may depend on its localization, which is expected to be
      influenced by the interaction with complex partners and regulators in response to
      cellular signals. Here, we present a detailed characterization of the interaction
      of the FRB domain with PA and how it is influenced by the surrounding membrane
      environment. On the basis of nuclear magnetic resonance- and circular dichroism
      monitored binding studies using different neutral and negatively charged lipids
      as well as different membrane mimetics (micelles, bicelles, and liposomes), the
      FRB domain may function as a conditional peripheral membrane protein. However,
      the data for the isolated domain just indicate an increased affinity for
      negatively charged lipids and membrane patches but no specific preference for PA
      or PA-enriched regions. The membrane-mimetic environment induces strong
      conformational changes that largely maintain the alpha-helical secondary
      structure content but presumably disperse the helices in the lipidic environment.
      Consistent with overlapping binding surfaces for different lipids and the FKBP12
      rapamycin complex, binding of the inhibitor complex protects the FRB domain from
      interactions with membrane mimetics at lower lipid concentrations.

PMID- 22620486
TI  - Clinicopathological study of 81 cases of localized and systemic scleroderma.
AB  - BACKGROUND: Scleroderma is a connective tissue disease that includes localized
      and systemic forms. Our recent encounter with a morphea case exhibiting prominent
      perineural inflammation microscopically prompted us to assess the features of all
      patients diagnosed with morphea/scleroderma at our institution.
      OBJECTIVE/METHODS: To describe the clinicopathological features of all patients
      diagnosed with morphea/scleroderma at American University of Beirut Medical
      Center (AUB-MC) between 1999 and 2010, and compare our findings with those
      published in the literature. RESULTS: A total of 81 cases (63 women and 18 men)
      were identified, of which 73 were localized (morphea) and eight were systemic
      scleroderma. Clinically, plaque type morphea was the most common variant both in
      adults and children, and seven (9%) cases of morphea were associated with lichen
      sclerosis et atrophicus (LSA). Histopathologically, perineural inflammation was
      observed in 49% of cases, and may serve, in addition to other features including
      lichen sclerosis-like changes (observed in exclusively nine cases of morphea),
      more diffuse dermal and less subcutaneous sclerosis, and intense inflammation, as
      clues favouring diagnosis of morphea over systemic sclerosis. CONCLUSION: The
      features of morphea/scleroderma patients in this study are generally comparable
      to those published in the literature, with few differences. Clinically, plaque
      type morphea was the most common variant both in adults and children and LSA was
      a frequent association. Histopathologically, perineural inflammation was commonly
      observed and may serve in addition to lichen sclerosis-like changes and intense
      inflammation as clues favouring diagnosis of morphea over systemic sclerosis.

PMID- 22620487
TI  - Influence of sildenafil on genital engorgement in women with female sexual
      arousal disorder.
AB  - INTRODUCTION: We previously described dynamic, noncontrast magnetic resonance
      imaging (MRI) of the female genitalia as a reproducible, nonintrusive, objective
      means of quantifying sexual arousal response in women without sexual
      difficulties. These studies showed an increase in clitoral engorgement ranging
      from 50 to 300% in healthy women during sexual arousal. AIM: This study sought to
      evaluate the genital arousal response in women with female sexual arousal
      disorder (FSAD) after administration of sildenafil and placebo. We performed a
      multicenter, double-blind, placebo-controlled, cross-over study to assess the
      clitoral engorgement response using dynamic MRI in women with FSAD after
      administering sildenafil and placebo followed by audiovisual sexual stimulation
      (AVSS). METHODS: Nineteen premenopausal women with FSAD underwent two MRI
      sessions. Subjects were randomized to receive either (i) sildenafil 100 mg during
      the first session followed by placebo during the second session, or (ii) placebo
      followed by sildenafil. During each session, baseline MR images were obtained
      while subjects viewed a neutral video. Subjects then ingested sildenafil or
      placebo. After 30 minutes, a series of MRIs were obtained at 3-minute intervals
      for 10 time points while subjects viewed AVSS. MAIN OUTCOME MEASURES: A positive
      sexual arousal response was achieved if clitoral volume increased >=50% from
      baseline. RESULTS: Thirteen of 19 (68%) subjects achieved a >=50% increase in
      clitoral engorgement from baseline when administered sildenafil or placebo 30
      minutes after dose administration. At 60 minutes after administration, 17/19
      (89%) subjects receiving sildenafil and 16/19 (84%) subjects receiving placebo
      had responded (P value 0.3173). CONCLUSIONS: Sildenafil did not augment the
      genital response in women with FSAD. Secondarily, a majority of women in this
      study did not have impaired clitoral engorgement as measured by MRI, suggesting
      that FSAD is not predominantly a disorder of genital engorgement.

PMID- 22620488
TI  - Anxiety as a marker of severity in acute mania.
AB  - OBJECTIVE: Anxiety has scarcely been studied in acute mania. The aim of this
      study was to assess anxiety symptoms during manic episodes and their impact on
      clinical outcomes. METHOD: Observational, cross-sectional multicentre study.
      Anxiety was measured using the Hamilton Anxiety Rating Scale (HARS). Bivariate
      and multiple linear regression analyses were performed using the HARS score as
      the dependent variable. RESULTS: Two hundred and forty-two patients admitted with
      a diagnosis of acute manic episode according to DSM-IV TR criteria and a Young
      Mania Rating Scale>20 were analysed. Mean age was 43 years (SD=11.9) and 57% were
      women. Forty-six per cent of patients (n=104) presented moderate to severe
      anxiety symptoms (HARS score>14). Anxiety was significantly associated with
      severity of manic symptoms (P<0.0001). Patients with anxiety had 20% longer
      hospitalizations (mean 21 days, CI95% 19.7-23.7). CONCLUSION: An association of
      anxiety symptoms with greater severity in acute mania was demonstrated. The close
      relationship between anxiety and manic symptoms highlights the need for greater
      clinical attention to anxiety in this population. Further studies are necessary
      to determine whether effective treatment of anxiety symptoms could improve
      clinical and care outcomes.

PMID- 22620489
TI  - Circulating nucleosomes and biomarkers of immunogenic cell death as predictive
      and prognostic markers in cancer patients undergoing cytotoxic therapy.
AB  - INTRODUCTION: Immunogenic cell death markers are released from apoptotic and
      necrotic cells upon pathologic or therapeutic causes and stimulate the innate and
      adaptive immune system. Cell death products such as nucleosomes, damage
      associated molecular pattern (DAMP) molecules such as the high-mobility group box
      1 protein (HMGB1) and its receptor of advanced glycation end products (sRAGE) are
      supposed to play an essential role in driving this process. However, this
      immunogenic activation may have dual effects, either by sensitizing the immune
      system for more efficient tumor cell removal or by creating a favorable tumor
      microenvironment that facilitates tumor growth, proliferation and invasiveness.
      AREAS COVERED: Here, we review recent findings on the relevance of serum
      nucleosomes, DNAse activity, HMGB1 and sRAGE as biomarkers for the diagnosis,
      prognosis and therapy prediction in cancer disease. EXPERT OPINION: In comparison
      with healthy controls, cancer patients demonstrated elevated serum levels of
      nucleosomes and HMGB1 while sRAGE levels were decreased. During locoregional and
      systemic cytotoxic therapies, a high release of nucleosomes and HMGB1 as well as
      low release of sRAGE before and during the initial phase of the treatment was
      found to be associated with poor response to the therapy and patient survival.
      Therefore, immunogenic cell death markers are promising tools for the prognosis,
      therapy prediction and monitoring in cancer patients.

PMID- 22620490
TI  - Acoustically detected year-round presence of right whales in an urbanized
      migration corridor.
AB  - Species' conservation relies on understanding their seasonal habitats and
      migration routes. North Atlantic right whales (Eubalaena glacialis), listed as
      endangered under the U.S. Endangered Species Act, migrate from the southeastern
      U.S. coast to Cape Cod Bay, Massachusetts, a federally designated critical
      habitat, from February through May to feed. The whales then continue north across
      the Gulf of Maine to northern waters (e.g., Bay of Fundy). To enter Cape Cod Bay,
      right whales must traverse an area of dense shipping and fishing activity in
      Massachusetts Bay, where there are no mandatory regulations for the protection of
      right whales or management of their habitat. We used passive acoustic recordings
      of right whales collected in Massachusetts Bay from May 2007 through October 2010
      to determine the annual spatial and temporal distribution of the whales and their
      calling activity. We detected right whales in the bay throughout the year, in
      contrast to results from visual surveys. Right whales were detected on at least
      24% of days in each month, with the exception of June 2007, in which there were
      no detections. Averaged over all years, right whale calls were most abundant from
      February through May. During this period, calls were most frequent between 17:00
      and 20:00 local time; no diel pattern was apparent in other months. The spatial
      distribution of the approximate locations of calling whales suggests they may use
      Massachusetts Bay as a conduit to Cape Cod Bay in the spring and as they move
      between the Gulf of Maine and waters to the south in September through December.
      Although it is unclear how dependent right whales are on the bay, the discovery
      of their widespread presence in Massachusetts Bay throughout the year suggests
      this region may need to be managed to reduce the probability of collisions with
      ships and entanglement in fishing gear.

PMID- 22620491
TI  - Change over time (2007-2009) in HIV preventive behaviours, evidence from two
      serial population-based surveys in rural Zimbabwe.
AB  - OBJECTIVE: To assess reported HIV knowledge and attitudes, sexual behaviours and
      HIV testing in Zimbabwe. METHODS: Representative household surveys of all 18-24
      year olds and a proportion of 25-44 year olds were conducted in six purposefully
      selected rural districts in two provinces in 2007 and 2009. Both surveys used the
      same methods and questionnaires. We compared differences in reported HIV
      knowledge, sexual behaviours and HIV testing, controlling for differences in
      socio-demographics at baseline, using cross-tabulations and multivariate
      regression analyses. RESULTS: Analysis was restricted to districts included in
      both baseline (n = 1891) and mid-term (n = 2746) surveys. Comparisons indicate
      increased reports of HIV knowledge (35%vs. 22% had high knowledge) and more
      favourable individual attitudes towards HIV. There was an increase in reported
      HIV testing (men: 41%vs. 31%, women: 55%vs. 36%) and condom use (men: adjusted
      odds ratio (AOR) = 1.35, women: AOR = 1.22) and a decrease in number of sexual
      partners (men: 67%vs. 49% reported 1 partner/previous 6 months, women: 77%vs.
      68%). CONCLUSIONS: As Zimbabwe continues to document declines in HIV prevalence,
      this analysis offers insight into recent and continuing positive changes in
      knowledge, attitudes and behaviours among the rural population.

PMID- 22620493
TI  - The effect of low vision rehabilitation in diabetic eye disease: a randomised
      controlled trial protocol.
AB  - PURPOSE: Current research highlights a rising incidence of diabetes and its
      complications. Diabetic retinopathy is the leading cause of blindness within the
      working-age population of the United Kingdom. Increasing severity of retinopathy
      is associated with reduced visual function and participation in daily living.
      Only 8% of those referred to Moorfields Eye Hospital's low vision clinic have
      diabetic eye disease, a value less than prevalence figures for diabetes would
      predict. The lack of evidence for effectiveness of low vision intervention in
      this patient group could be responsible. Therefore, in line with CONSORT
      guidance, we present the methodology of the first randomised controlled trial to
      quantify the effect of low vision rehabilitation on people with diabetic eye
      disease. METHODS: One hundred participants were recruited into four retinopathy
      severity groups based on their diagnosis according to the English National
      Screening Programme Grading Protocol. Participants were randomised to either
      immediate intervention (1-2 weeks after enrollment) or delayed (control)
      intervention (3 months after enrollment). Intervention was a standard low vision
      assessment performed in a hospital clinic. The Activity Inventory (AI), was
      administered to all participants by telephone within 1 week of enrollment (before
      any intervention) and repeated at 3 and 6 months. RESULTS: One hundred
      participants (Type 1: 28, Type 2: 72; male: 62, female 38) have been recruited.
      Median habitual distance acuity was 0.19 logMAR (6/9, 20/30), with an
      interquartile range of 0.06-0.30 logMAR (6/7.5-6/12, 20/25-20/40). AI responses
      were scored by Rasch analysis, providing a measure of visual ability. Median
      baseline visual ability was 1.64 logits, with an interquartile range of 0.60-3.75
      logits. Difference in mean change in visual ability between intervention groups
      will be assessed 3 months (primary outcome) and 6 months (secondary outcome)
      after enrollment. CONCLUSIONS: This is the first randomised controlled trial
      investigating the effectiveness of low vision rehabilitation for people with
      diabetic eye disease. With recruitment already complete, it is hoped this work
      will be the first step in guiding referral criteria for those with diabetic eye
      disease into the low vision service.

PMID- 22620494
TI  - Sputum tobramycin concentrations in cystic fibrosis patients with repeated
      administration of inhaled tobramycin.
AB  - BACKGROUND: Dosing of tobramycin solution for inhalation (TSI) in cystic fibrosis
      (CF) patients was based on single-dose pharmacokinetic studies. This
      investigation was prompted by evidence of possible antibiotic accumulation in
      respiratory secretions with repeated dosing. The objectives were to evaluate
      whether tobramycin accumulates in respiratory secretions with repeated
      inhalation, compare total and biologically active tobramycin concentrations in CF
      sputum, and evaluate sputum induction for obtaining secretions for drug
      concentration assay. METHODS: Individuals with CF >=10 years of age were enrolled
      at the beginning of a course of TSI, 300 mg twice daily for 28 days. Two study
      visits were conducted, 1-2 days and 24-28 days after initiation of TSI treatment.
      Induced sputum and expectorated sputum samples were collected for measurement of
      trough and peak tobramycin concentrations at each visit. Total tobramycin
      concentrations were measured by high-pressure liquid chromatography and bioactive
      concentrations by bioassay. RESULTS: Twenty participants completed the study.
      Trough concentrations were similar at visits 1 and 2, as were peak
      concentrations. Trough bioactive and total tobramycin concentrations were similar
      (mean ratio 1.2, 95% CI 0.56, 1.87), but peak bioactive concentrations were
      significantly lower than peak total concentrations (mean ratio 0.33, 95% CI 0.23,
      0.44). Sputum induction was well tolerated. CONCLUSIONS: No evidence of
      significant drug accumulation in respiratory secretions with repeat dosing of TSI
      was seen. Peak bioactive concentrations, although lower than peak total
      concentrations, were still generally well within the bactericidal range. Sputum
      induction as a method for determining airway drug concentrations appears safe and
      feasible.

PMID- 22620496
TI  - Hydration, sweat and thermoregulatory responses to professional football training
      in the heat.
AB  - AbstThis study examined the relationship between intensity of training and
      changes in hydration status, core temperature, sweat rate and composition and
      fluid balance in professional football players training in the heat. Thirteen
      professional football players completed three training sessions; "higher
      intensity" (140 min; HI140), "lower-intensity" (120 min; LI120) and "game
      simulation" (100 min; GS100). Movement demands were measured by Global
      Positioning System, sweat rate and concentration were determined from dermal
      patches and body mass change. Despite similar environmental conditions (26.9 +/-
      0.1  degrees C and 65.0 +/- 7.0% relative humidity [Rh]), higher relative speeds
      (m . min(-1)) and increased perceptions of effort and thermal strain were
      observed in HI140 and GS100 compared with LI120 (P < 0.05). Significantly (P <
      0.05) greater sweat rate (L . h(-1)) and electrolyte losses (g) were observed in
      HI140 and GS100 compared with LI120. Rate of rise in core temperature was
      correlated with mean speed (r = 0.85), session rating of perceived exertion
      (sRPE) (r = 0.61), loss of potassium (K+) (r = 0.51) sweat rate (r = 0.49), and
      total sweat loss (r = 0.53), with mean speed the strongest predictor. Sodium
      (Na+) (r = 0.39) and K+ (r = 0.50) losses were associated with total distance
      covered. In hot conditions, individualised rehydration practices should be
      adopted following football training to account for differences in sweat rate and
      electrolyte losses in response to intensity and overall activity within a
      session.

PMID- 22620495
TI  - Critical analysis of treatment trials of rhesus macaques infected with Borrelia
      burgdorferi reveals important flaws in experimental design.
AB  - A critical analysis of two treatment trials of Chinese rhesus macaques infected
      with Borrelia burgdorferi indicates that insufficient attention was placed on
      documenting the blood levels, pharmacokinetics, and pharmacodynamic parameters of
      the antibiotics used in this host. Consequently, it is impossible to conclude
      that the findings have validity in judging the efficacy of doxycycline or
      ceftriaxone for the treatment of Borrelia burgdorferi in this animal model.

PMID- 22620497
TI  - A model of the response of visual area V2 to combinations of orientations.
AB  - The role of the V2 area in visual processing is still almost entirely unexplored.
      Recently, several studies revealed the tuning of V2 neurons in the macaque to
      stimuli consisting of two segments with different orientations. By measuring
      orientation tuning inside subunits of the overall receptive field, units with non
      uniform orientation selectivity have been found. In this work, the emergence of a
      computational organization supporting similar responses is explored, using an
      artificial model of cortical maps. This model, called LISSOM (Laterally
      Interconnected Synergetically Self-Organizing Map) includes excitatory and
      inhibitory lateral connections. In this simulation two LISSOM maps are arranged
      as V1 and V2 areas. In the first area, the classical domains of orientation
      selectivity develop, while in V2 most neurons become sensitive to pairs of
      orientations. The overall activation of these units depend on the presence of
      oriented segments at a finer grain than the whole receptive fields, with complex
      nonlinear interactions.

PMID- 22620498
TI  - Insights into melanoma: targeting the mTOR pathway for therapeutics.
AB  - INTRODUCTION: Cutaneous melanoma represents < 5% of all skin cancers, but is
      responsible for the majority of skin cancer-related deaths. Ocular melanoma is
      the most common primary eye tumor in adults, and accounts for approximately 5% of
      all melanomas. Despite new diagnostic and therapeutic tools, the overall survival
      of patients treated for melanoma has not improved and most patients die of
      metastatic disease. Therefore, clarification of the molecular mechanisms
      underlying the etiopathogenesis of cutaneous and ocular melanomas may help
      determining the prognosis and tailoring therapy of patients harboring melanomas.
      AREAS COVERED: In this review the authors aim to survey relevant research in the
      molecular mechanisms underlying melanomagenesis, and therapies under evaluation
      with emphasis in the mTOR pathway. EXPERT OPINION: Despite an increasingly
      understanding of the genetics and biochemistry of melanoma, the mechanisms
      underlying their complex interactions are still poorly understood. Their
      clarification will lead to more successful therapeutic strategies and evidence
      based management of patients with melanoma. More active drug combinations
      together with appropriate melanoma patient stratification based on molecular
      biomarkers will be essential for new advances in melanoma therapy.

PMID- 22620499
TI  - On-surface formation of metal nanowire transparent top electrodes on CdSe
      nanowire array-based photoconductive devices.
AB  - A simple wet chemical approach was developed for a unique on-surface synthesis of
      transparent conductive films consisting of ultrathin gold/silver nanowires
      directly grown on top of CdSe nanowire array photoconductive devices enclosed in
      polycarbonate membranes. The metal nanowire film formed an ohmic contact to the
      semiconductor nanowires without additional treatment. The sheet resistance and
      transparency of the metal nanowire arrays could be controlled by the number of
      metal nanowire layers deposited, ranging from ~98-99% transmission through the
      visible range and several kOhm/sq sheet resistance for a single layer, to 80-85%
      transmission and ~100 Ohm/sq sheet resistance for 4 layers. 

PMID- 22620673
TI  - A novel CaSR mutation presenting as a severe case of neonatal familial
      hypocalciuric hypercalcemia.
AB  - BACKGROUND: Familial Hypocalciuric Hypercalcemia (FHH) is a generally benign
      disorder caused by heterozygous inactivating mutations in the Calcium-Sensing
      Receptor (CaSR) gene resulting in altered calcium metabolism. OBJECTIVE: We
      report a case of unusually severe neonatal FHH due to a novel CaSR gene mutation
      that presented with perinatal fractures and moderate hypercalcemia. CASE
      OVERVIEW: A female infant was admitted at 2 weeks of age for suspected non
      accidental trauma (NAT). Laboratory testing revealed hypercalcemia (3.08 mmol/L),
      elevated iPTH (20.4 pmol/L) and low urinary calcium clearance (0.0004).
      Radiographs demonstrated multiple healing metaphyseal and rib fractures and
      bilateral femoral bowing. The femoral deformity and stage of healing were
      consistent with prenatal injuries rather than non-accidental trauma (NAT).
      Treatment was initiated with cholecalciferol, 400 IU/day, and by 6 weeks of age,
      iPTH levels had decreased into the high-normal range. Follow up radiographs
      demonstrated marked improvement of bone lesions by 3 months. A CaSR gene mutation
      study showed heterozygosity for a T>C nucleotide substitution at c.1664 in exon
      6, resulting in amino acid change I555T in the extracellular domain consistent
      with a missense mutation. Her mother does not carry the mutation and the father
      is unknown. At 18 months of age, the child continues to have relative
      hyperparathyroidism and moderate hypercalcemia but is otherwise normal.
      CONCLUSION: This neonate with intrauterine fractures and demineralization,
      moderate hypercalcemia and hyperparathyroidism was found to have a novel
      inactivating missense mutation of the CaSR not detected in her mother. Resolution
      of bone lesions and reduction of hyperparathyroidism was likely attributable to
      the natural evolution of the disorder in infancy as well as the mitigating effect
      of cholecalciferol treatment.

PMID- 22620672
TI  - Inherited thrombophilia and IVF failure: the impact of coagulation disorders on
      implantation process.
AB  - In connection with the embryo acceptance process after IVF procedure, endometrial
      cells surface receptors, extracellular matrix (ECM) molecules, endothelium and
      blood circulation factors were involved in remodelling of endometrium.
      Plasminogen activator inhibitor type 1 plays a significant role during the early
      phases of placental vascular remodelling and regulates the trophoblast invasion
      through controlling plasmin activity. Endometrial cell surface protein integrin
      alphaV/beta3, responsible for the adhesion of the embryo, has had also the same
      subunit beta3, which is component of integrin alphaIIb/beta3 connected with
      platelet aggregability. Prothrombin, furthermore, has had a debatable effect upon
      endothelial and mesenchymal cells and possible contribution on embryo vascular
      development. Confoundable data have been present about the role of coagulation
      factor V and its role for implantation. These and other coagulation factors have
      relatively common gene polymorphisms that enhanced their activity. This review
      discusses the effect of increased coagulation activity on implantation process,
      which is not yet fully determined. The establishment of the positive or negative
      impact of mother hypercoagulability on the success of embryo implantation after
      assisted reproduction technology could determine the timing of preventing
      anticoagulant therapy in women with history of early embryo loss.

PMID- 22620674
TI  - Approximate scheme for calculating van der Waals interactions between finite
      cylindrical volume elements.
AB  - A successful approach to calculating van der Waals (vdW) forces between irregular
      bodies is to divide the bodies into small cylindrical volume elements and
      integrate the vdW interactions between opposing elements. In this context it has
      been common to use Hamaker's expression for parallel plates to approximate the
      vdW interactions between the opposing elements. This present study shows that
      Hamaker's vdW expression for parallel plates does not accurately describe the vdW
      interactions for co-axial cylinders having a ratio of cylinder radius to
      separation distance (R/D) of 10 or less. This restricts the systems that can be
      simulated using this technique and explicitly excludes consideration of
      topographical or compositional variations at the nanoscale for surfaces that are
      in contact or within a few nm of contact. To address this limitation, approximate
      analytical expressions for nonretarded vdW forces between finite cylinders in
      different orientations are derived and are shown to produce a high level of
      agreement with forces calculated using full numerical solutions of the
      corresponding Hamaker's equations. The expressions developed here allow accurate
      calculation of vdW forces in systems where particles are in contact or within a
      few nm of contact with surfaces and the particles and/or surfaces have
      heterogeneous nanoscale morphology or composition. These calculations can be
      performed at comparatively low computational cost compared to the full numerical
      solution of Hamaker's equations.

PMID- 22620675
TI  - Toward rational design of amine solutions for PCC applications: the kinetics of
      the reaction of CO2(aq) with cyclic and secondary amines in aqueous solution.
AB  - The kinetics of the fast reversible carbamate formation reaction of CO(2)(aq)
      with a series of substituted cyclic secondary amines as well as the noncyclic
      secondary amine diethanolamine (DEA) has been investigated using the stopped-flow
      spectrophotometric technique at 25.0  degrees C. The kinetics of the slow
      parallel reversible reaction between HCO(3)(-) and amine has also been determined
      for a number of the amines by (1)H NMR spectroscopy at 25.0  degrees C. The rate
      of the reversible reactions and the equilibrium constants for the formation of
      carbamic acid/carbamate from the reactions of CO(2) and HCO(3)(-) with the amines
      are reported. In terms of the forward reaction of CO(2)(aq) with amine, the order
      with increasing rate constants is as follows: diethanolamine (DEA) < morpholine
      (MORP) ~ thiomorpholine (TMORP) < N-methylpiperazine (N-MPIPZ) < 4
      piperidinemethanol (4-PIPDM) ~ piperidine (PIPD) < pyrrolidine (PYR). Both 2
      piperidinemethanol (2-PIPDM) and 2-piperidineethanol (2-PIPDE) do not form
      carbamates. For the carbamate forming amines a Bronsted correlation relating the
      protonation constant of the amine to the carbamic acid formation rate and
      equilibrium constants at 25.0  degrees C has been established. The overall
      suitability of an amine for PCC in terms of kinetics and energy is discussed.

PMID- 22620676
TI  - A change in the epidemiology of bovine cysticercosis in Israel between 1973 and
      2008 due to import of live cattle.
AB  - Bovine cysticercosis (BC) is an important disease because of its zoonotic nature.
      There is a significant variation in the prevalence of BC in different countries,
      ranging from <0.01% to more than 20%. In this study, we followed the changes of
      BC prevalence in Israel during the last four decades and examined its association
      with import of live cattle. During 1973-2007, 629,549 cattle were subjected to
      post-mortem inspection conducted in 'Marbek' slaughterhouse located in the south
      of Israel. A specific comparison was made between the prevalence of BC in local
      and imported cattle during 2003-2007. Of 629,549 cattle, 2568 were infected with
      Cysticercus bovis (0.4%). From 1980, there was a gradual decrease in the
      prevalence of BC (R(2) = 0.53) with exceptional peaks. Moreover, from 1973 to
      1998, only 4% of the documented cases appeared in outbreaks as opposed to 38%
      after 1998 when mass importation of live cattle to Israel was initiated. All of
      these late outbreak cases appeared in imported cattle of which 95% originated
      from Australia. During the years 2002-2007, importation from Australia was found
      as a significant risk factor for infection with BC, with prevalence in these
      cattle reaching 1.8% in 2006. The time from importation to BC detection suggests
      that infection occurred either in Australia or during the transport into Israel.
      We conclude that despite a reduction in the prevalence of BC as a result of a
      possible improvement in sanitary conditions at the farms, meticulous meat
      inspection is still essential in Israel and possibly in other developed countries
      exporting and importing live cattle.

PMID- 22620677
TI  - Sesquiterpenoids from Incarvillea arguta: absolute configuration and biological
      evaluation.
AB  - Diincarvilones A-D (1-4), incarvilone A (5), and a known compound, argutosine B
      (6), were isolated from Incarvillea arguta. The structures, including the
      absolute configurations of the new compounds, were determined by NMR
      spectroscopy, X-ray diffraction analysis, CD spectroscopy, and a variety of
      computational methods. The biological properties of these substances, including
      effects on intracellular Ca(2+) influx, nitric oxide (NO) production, and human
      cancer cells, were evaluated. The results showed that at the concentration of 10
      MUM (in HBSS buffer) diincarvilones A and B cause a persistent increase in
      cytoplasmic calcium levels in A549 cells.

PMID- 22620678
TI  - The reliability of a portable clinical force plate used for the assessment of
      static postural control: repeated measures reliability study.
AB  - BACKGROUND: Force plates are frequently used for postural control assessments
      but they are expensive and not widely available in most clinical settings.
      Increasingly, clinicians are using this technology to assess patients, however,
      the psychometric properties of these less sophisticated force plates is
      frequently unknown. The purposes of the study were to examine the test-retest
      reliability of a force plate commonly used by clinicians and to explore the
      effect of using the mean value from multiple repetitions on reliability. METHODS:
      Thirty healthy volunteer adults were recruited. Postural control measures were
      obtained using the Midot Posture Scale Analyzer (MPSA). Data were collected in 2
      sessions. Five successive repetitions each of 60 seconds duration were obtained
      from each participant in each session. RESULTS: The reliability coefficients
      obtained using single measures were low (ICC3,1 = 0.06 to 0.53). The average of
      two measures allowed for reliable measurements of COP mean velocity and average
      location of COP. The average of three and five measures was required to obtain
      acceptable reliability (ICC >= 0.70) of relative weight bearing on legs and sway
      area, respectively. Higher measurement precision values were seen by averaging
      four or five repetitions for all variables. CONCLUSION: Single measures did not
      provide reliable estimates of postural sway, and the averaging of multiple
      repetitions was necessary to achieve acceptable levels of measurement error. The
      number of repetitions required to achieve reliable data ranged from 2 to 5.
      Clinicians should be wary of using single measures derived from similar equipment
      when making decisions about patients.

PMID- 22620679
TI  - Bronchoalveolar lavage fluid exosomes contribute to cytokine and leukotriene
      production in allergic asthma.
AB  - BACKGROUND: Leukotrienes (LTs) are potent pro-inflammatory mediators involved in
      asthma. Exosomes, nanosized vesicles released from various cells, can stimulate
      or down-regulate immune responses, depending on the state and nature of the
      originating cell. We have recently shown an altered exosome profile in
      bronchoalveolar lavage fluid (BALF) of patients with sarcoidosis, but their role
      in asthma is unknown. Our aims were to investigate whether exosomes from BALF
      have LT biosynthetic capacity and to explore phenotypic and functional
      characteristics of BALF exosomes in asthma. METHODS: Bronchoalveolar lavage fluid
      exosomes were collected from healthy individuals (n = 13) and patients with mild
      allergic asthma to birch pollen (n = 12) before and after birch allergen
      provocation. Exosomes were characterized by flow cytometry and Western blot.
      Their capacity to induce IL-8 and LT production in the human bronchial epithelial
      cell (BEC) line 16HB14o- was measured by ELISA and reverse-phase HPLC,
      respectively. RESULTS: Compared to BALF exosomes from healthy individuals, BALF
      exosomes from asthmatics displayed higher levels of exosome-associated markers,
      such as the tetraspanins CD63 and CD81 and the scavenger receptor CD36. No major
      differences were observed between BALF exosomes from before and after allergen
      provocation. Furthermore, we show that BALF exosomes contain enzymes for LT
      biosynthesis. The effect of exosomes to promote LTC(4) and IL-8 release in BEC
      was significantly increased for exosomes from asthmatics, and the CysLT(1)
      receptor antagonist Montelukast reduced exosome-induced IL-8 secretion.
      CONCLUSIONS: Bronchoalveolar lavage fluid exosomes from asthmatic and healthy
      individuals exhibit distinct phenotypes and functions. BALF exosomes from
      asthmatics might contribute to subclinical inflammation by increasing cytokine
      and LTC(4) generation in airway epithelium.

PMID- 22620680
TI  - gamma-Synuclein: seeding of alpha-synuclein aggregation and transmission between
      cells.
AB  - Protein misfolding and aggregation is a ubiquitous phenomenon associated with a
      wide range of diseases. The synuclein family comprises three small naturally
      unfolded proteins implicated in neurodegenerative diseases and some forms of
      cancer. alpha-Synuclein is a soluble protein that forms toxic inclusions
      associated with Parkinson's disease and several other synucleinopathies. However,
      the triggers inducing its conversion into noxious species are elusive. Here we
      show that another member of the family, gamma-synuclein, can be easily oxidized
      and form annular oligomers that accumulate in cells in the form of deposits.
      Importantly, oxidized gamma-synuclein can initiate alpha-synuclein aggregation.
      Two amino acid residues in gamma-synuclein, methionine and tyrosine located in
      neighboring positions (Met(38) and Tyr(39)), are most easily oxidized. Their
      oxidation plays a key role in the ability of gamma-synuclein to aggregate and
      seed the aggregation of alpha-synuclein. gamma-Synuclein secreted from neuronal
      cells into conditioned medium in the form of exosomes can be transmitted to glial
      cells and cause the aggregation of intracellular proteins. Our data suggest that
      post-translationally modified gamma-synuclein possesses prion-like properties and
      may induce a cascade of events leading to synucleinopathies.

PMID- 22620681
TI  - Designing quantum rods for optimized energy transfer with firefly luciferase
      enzymes.
AB  - The bioluminescence resonance energy transfer (BRET) between firefly luciferase
      from Photinus pyralis (Ppy) with core/shell semiconductive quantum rods (QRs) has
      been studied as a function of QR aspect ratio and internal microstructure. The
      QRs were found to be ideal energy acceptors, and Ppy-to-core distances were
      optimized using rod-in-rod microstructures that were achieved by the synthetic
      control of rod morphology, surface chemistry, and Ppy:QR loading. The BRET ratios
      of >44 measured are the highest efficiencies to date.

PMID- 22620682
TI  - Comparative analysis of the use of complementary and alternative medicine by
      Korean patients with androgenetic alopecia, atopic dermatitis and psoriasis.
AB  - BACKGROUND: Complementary and alternative medicine (CAM) is being increasingly
      used among Koreans with chronic dermatologic diseases, such as androgenetic
      alopecia (AGA), atopic dermatitis (AD) and psoriasis. OBJECTIVE: To quantify the
      usage of CAM in Korean patients with AGA, AD or psoriasis, and to offer valid
      information for the physicians frequently encountering such disorders. METHODS:
      Outpatients (n = 678) from three tertiary hospitals were investigated
      independently by constructed and self-directed questionnaire. RESULTS: Of the
      respondents, 62.1% (421/678) of the subjects reported current or previous use of
      CAM for their dermatologic conditions (AGA, 67.2%; AD, 68.9%; psoriasis, 46.6%).
      In AGA, topical applicants (50.2%) were most often used, followed by dietary
      therapy and health supplements. In AD, bath therapy (39.4%) was most often used,
      followed by oriental medicine and topical applicants. In psoriasis, oriental
      medicine (33.9%) was most frequently used, followed by bath therapy and health
      supplements. The proportion of patients who believed that CAM helped to improve
      their skin condition was relatively low (AGA, 16.1%; AD, 31.7%; psoriasis,
      15.0%). LIMITATIONS: The results may not be applicable to other countries and
      generalized to general populations. CONCLUSION: These results indicate that CAM
      is widely used in Korean patients with chronic dermatological diseases despite
      their dissatisfactions. Thus, the advantages and disadvantages of CAM must be
      considered before its clinical practice.

PMID- 22620683
TI  - alpha-lipoic acid inhibits high glucose-induced apoptosis in HIT-T15 cells.
AB  - High blood glucose plays an important role in the pathogenesis of diabetes. alpha
      lipoic acid (LA) has been used to prevent and treat diabetes, and is thought to
      act by increasing insulin sensitivity in many tissues. However, whether LA also
      has a cytoprotective effect on pancreatic islet beta cells remains unclear. In
      this study, we assessed whether LA could inhibit apoptosis in beta cells exposed
      to high glucose concentrations. HIT-T15 pancreatic beta cells were treated with
      30 mmol/L glucose in the presence or absence of 0.5 mmol/L LA for 8 days. LA
      significantly reduced the numbers of apoptotic HIT-T15 cells and inhibited the
      cell overgrowth normally induced by high glucose treatment. Additionally, LA
      inhibited insulin expression and secretion in HIT-T15 cells induced by high
      glucose. Further study demonstrated that LA upregulated Pdx1 and Bcl2 gene
      expression, reduced Bax gene expression, and promoted phosphorylation of Akt in
      HIT-T15 cells treated with high glucose. Intriguingly, knockdown of Pdx1
      expression partially offset the anti-apoptotic effect of LA. However, inhibition
      of Akt by PI3K/AKT antagonist LY294002 only slightly reversed the anti-apoptosis
      effect of LA and mildly decreased the gene expression level of Pdx1 (P > 0.05).
      Moreover, LA only slightly attenuated reactive oxygen species (ROS) production
      and augmented mitochondrial membrane potential. Therefore, our data suggest that
      alpha-lipoic acid can effectively attenuate high glucose-induced HIT-T15 cell
      apoptosis probably by increasing Pdx1 expression. These findings provide a new
      interpretation on the role of LA in the treatment of diabetes.

PMID- 22620684
TI  - Clinical improvement and satisfaction with biologic therapy in patients with
      severe plaque psoriasis: results of a European cross-sectional observational
      study.
AB  - BACKGROUND: Efficacy of biologic therapies for psoriasis has been demonstrated in
      randomized trials, but effectiveness in real-world settings has yet to be fully
      determined. OBJECTIVE: To compare clinical improvement and treatment satisfaction
      with biologic versus other therapies in patients with plaque psoriasis. METHODS:
      European dermatologists recruited psoriasis patients into an observational study.
      Dermatologists reported disease severity before and after starting current
      therapy; dermatologists and patients reported treatment satisfaction. RESULTS:
      These analyses included 2151 patients: topicals, n = 453; phototherapy, n = 666;
      conventional systemics, n = 683; biologics, n = 349. The percentage with severe
      disease declined from 70% before to 15% after biologics, a significantly greater
      decline than other therapies: topicals, 22-10%; phototherapy, 20-11%;
      conventional systemics, 49-15% (all p <= 0.03). Significantly more patients (59%)
      receiving biologics were satisfied with treatment versus topicals (45%),
      phototherapy (34%), or conventional systemics (50%) (all p < 0.001).
      Significantly more dermatologists were satisfied with biologics (60%) versus
      topicals (35%), phototherapy (26%), or conventional systemics (42%) (all p <
      0.001). CONCLUSIONS: In this study, more patients receiving biologic therapies
      improved from severe to moderate or mild psoriasis than patients on other
      treatments. More patients with plaque psoriasis and their dermatologists were
      satisfied with biologics than any other treatment.

PMID- 22620685
TI  - Cauda equina syndrome as the initial presenting clinical feature of
      medulloblastoma: a case report.
AB  - INTRODUCTION: Medulloblastoma is one of the most common pediatric brain
      malignancies. The usual presenting clinical features are related to posterior
      fossa syndrome or/and hydrocephalus. Cauda equina syndrome is a very rare
      presentation for this disease. CASE PRESENTATION: We describe the case of a three
      year-old boy with cauda equina syndrome as the initial presenting clinical
      feature for medulloblastoma. He was initially diagnosed as having a spinal tumor
      by magnetic resonance imaging scan. Subsequently, a cranial magnetic resonance
      imaging scan revealed a posterior fossa tumor with features of dissemination. He
      had substantial improvement after treatment. This case report is complemented by
      a literature review related to this unusual presentation. CONCLUSIONS:
      Medulloblastoma primarily presenting with cauda equina syndrome is very rare.
      However, spinal drop metastasis should be considered in the pediatric age group
      to avoid suboptimal management.

PMID- 22620687
TI  - Evaluation of a technique for measurement of flow-mediated vasodilation in
      healthy ponies.
AB  - OBJECTIVE: To determine between-pony and within-pony variations and interobserver
      and intraobserver agreements of a technique for measurement of flow-mediated
      vasodilation (FMD) in healthy ponies. ANIMALS: 6 healthy pony mares (weight
      range, 236 to 406 kg; body condition score range, 3/9 to 7/9; age range, 14 to 25
      years). PROCEDURES: In each pony, the left median artery was occluded with a
      blood pressure cuff (inflated to > 300 mm Hg for 5 minutes). Two-dimensional
      ultrasonographic images of the artery were recorded for 30 seconds before cuff
      inflation and for 2 minutes after cuff deflation. Maximum luminal diameters of
      arteries were compared with their baseline diameters to calculate FMD (relative
      percentage increase in luminal size). Images were obtained from 6 ponies 1 time
      and from 1 pony 6 times. Independent analysis of images was performed by 2
      investigators, 1 of whom analyzed images on 2 occasions. RESULTS: Mean +/- SD FMD
      in 6 ponies (1 time) was 12.57 +/- 4.28% and in 1 pony (6 times) was 7.30 +/-
      2.11%. Between-pony and within-pony coefficients of variation were 34.09% and
      28.84%, respectively. Interobserver agreement was fair (intraclass correlation
      coefficient, 0.47); intraobserver agreement was poor (intraclass correlation
      coefficient, 0.30). CONCLUSIONS AND CLINICAL RELEVANCE: FMD was identified and
      measured in ponies. Measurement of FMD is used to assess endothelial function in
      humans and has been investigated in dogs. Measurement of FMD in ponies appeared
      to be feasible and could be used to assess endothelial function (to determine
      predisposition for development of laminitis or cardiovascular diseases).

PMID- 22620688
TI  - Development of an automated plasmapheresis procedure for the harvest of equine
      plasma in accordance with current good manufacturing practice.
AB  - OBJECTIVE: To develop a high-speed, continuous-flow, automated plasmapheresis
      procedure for the high-volume harvest of equine plasma in accordance with current
      good manufacturing practice. ANIMALS: 143 horses (predominantly draft breeds)
      between 3 and 10 years of age at the time of purchase. PROCEDURES: Adaptations
      were made to automated plasmapheresis instruments and sterile disposable
      collection sets, which allowed for dual-instrument, continuous-flow operation.
      Donor horses were connected to the apparatus via 2 catheters (1 inserted in each
      jugular vein). The instruments removed whole blood from donors, fractionated the
      blood, diverted plasma to collection bags, and simultaneously returned
      concentrated cells to the donors. Plasmapheresis was performed on donor horses at
      14-day intervals with a maximum of 22 mL of plasma/kg of donor body weight
      harvested during each plasmapheresis procedure. RESULTS: During a 5-year period,
      3,240 plasmapheresis procedures were performed and > 50,000 L of sterile equine
      plasma was harvested in accordance with current good manufacturing practice.
      Donors typically remained calm during the plasmapheresis procedures and tolerated
      the procedures well. The high-volume and frequent plasma harvest did not result
      in sustained hypoproteinemia in donor horses. Adverse events associated with the
      automated plasmapheresis technique were infrequent, and the recurrence of adverse
      events was minimized by making minor adjustments to the procedure. CONCLUSIONS
      AND CLINICAL RELEVANCE: The automated plasmapheresis procedure described in this
      report can be used to safely harvest equine plasma or to perform therapeutic
      plasmapheresis in horses.

PMID- 22620689
TI  - Effects of serial harvest of plasma on total plasma protein and total
      immunoglobulin G concentrations in donor horses involved in a plasmapheresis
      program.
AB  - OBJECTIVE: To determine the effects of intensive serial plasmapheresis on total
      plasma protein and total IgG concentrations in donor horses involved in a
      plasmapheresis program. ANIMALS: 18 horses (13 mares and 5 geldings; 13 Belgians,
      3 Percherons, 1 Standardbred, and 1 warmblood) ranging from 7 to 14 years of age
      (mean +/- SD, 10 +/- 3 years) and weighing 822 +/- 128 kg. PROCEDURES: Horses
      from which 22 mL of plasma/kg of donor body weight was harvested at 14-day
      intervals for a minimum of 8 consecutive plasmapheresis donations were
      retrospectively selected for use in the evaluation. Automated plasmapheresis
      procedures were performed by use of 2 modified plasmapheresis instruments/donor
      horse. Plasma samples were obtained at each donation and used for determination
      of total protein and total IgG concentrations. Total plasma protein
      concentrations were determined via refractometry. A commercially available ELISA
      was used to determine total equine IgG concentrations. RESULTS: The 18 donor
      horses were used in 8 to 19 serial donations (mean +/- SD, 13 +/- 3 donations)
      during the study. Donor horses had significant decreases in both plasma protein
      and IgG concentrations over the study period. CONCLUSIONS AND CLINICAL RELEVANCE:
      Serial plasmapheresis procedures caused significant decreases in both plasma
      protein and IgG concentrations in donor horses; however, decreases were not
      physiologically relevant. Performing plasmapheresis in horses in accordance with
      the evaluated automated plasmapheresis procedures did not result in a critical
      decrease in total plasma protein or total IgG concentrations.

PMID- 22620690
TI  - Kaolin-activated thromboelastography in echocardiographically normal cats.
AB  - OBJECTIVE: To determine reference values for kaolin-activated thromboelastography
      in echocardiographically normal cats. ANIMALS: 30 healthy cats without evidence
      of cardiomyopathy on echocardiographic examination. PROCEDURES: All cats
      underwent echocardiographic examination, the findings of which were reviewed by a
      board-certified cardiologist. Cats that struggled (n = 10) received mild sedation
      with butorphanol and midazolam IM to permit phlebotomy without interruption in
      jugular venous blood flow. Blood samples were collected for analysis of
      thromboelastography variables, PCV, total solids concentration, platelet count,
      activated partial thromboplastin time, prothrombin time, fibrinogen
      concentration, and antithrombin concentration. RESULTS: All 4 thromboelastography
      variables had < 5% mean intra-assay variability. Mean values were as follows:
      reaction time, 4.3 minutes; clotting time, 1.6 minutes; alpha angle, 66.5 degrees
      ; and maximum amplitude, 56.4 mm. Compared with nonsedated cats, cats that
      required sedation had a significantly shorter clotting time and greater alpha
      angle, whereas reaction time and maximum amplitude were not significantly
      different. CONCLUSIONS AND CLINICAL RELEVANCE: Kaolin-activated
      thromboelastography was a reliable test with unremarkable intra-assay variability
      in echocardiographically normal cats. Sedation may affect certain
      thromboelastography variables, but the effect is unlikely to be clinically
      important. It remains unknown whether subclinical cardiomyopathy has a
      significant effect on thromboelastography variables in cats.

PMID- 22620691
TI  - Evaluation of factors that affect analytic variability of urine protein-to
      creatinine ratio determination in dogs.
AB  - OBJECTIVE: To determine whether preanalytic and analytic factors affect
      evaluation of the urinary protein-to-creatinine (UPC) ratio in dogs. SAMPLE: 50
      canine urine samples. PROCEDURES: The UPC ratio was measured to assess the intra
      assay imprecision (20 measurements within a single session), the influence of
      predilution (1:10, 1:20, and 1:100) for urine creatinine concentration
      measurement, and the effect of storage at room temperature (approx 20 degrees C),
      4 degrees C, and -20 degrees C. RESULTS: The coefficient of variation at room
      temperature determined with the 1:20 predilution was < 10.0%, with the highest
      coefficients of variation found in samples with a low protein concentration or
      low urine specific gravity. This variability could result in misclassification of
      samples with UPC ratios close to the thresholds defined by the International
      Renal Interest Society to classify dogs as nonproteinuric (0.2), borderline
      proteinuric (0.21 to 0.50), or proteinuric (> 0.51). A proportional bias was
      found in samples prediluted 1:10, compared with samples prediluted 1:20 or 1:100.
      At room temperature, the UPC ratio did not significantly increase after 2 and 4
      hours. After 12 hours at room temperature and at 4 degrees C, the UPC ratio
      significantly increased. The UPC ratio did not significantly change during 3
      months of storage at -20 degrees C. CONCLUSIONS AND CLINICAL RELEVANCE: The intra
      assay precision of the UPC ratio was sufficiently low to avoid misclassification
      of samples, except for values close to 0.2 or 0.5. The optimal predilution ratio
      for urine creatinine concentration measurement was 1:20. A 1:100 predilution is
      recommended in samples with a urine specific gravity > 1.030. The UPC ratio must
      be measured as soon as samples are collected. Alternatively, samples should be
      immediately frozen to increase their stability and minimize the risk of
      misclassification of proteinuria.

PMID- 22620692
TI  - Correlation of hematocrit, platelet concentration, and plasma coagulation factors
      with results of thromboelastometry in canine whole blood samples.
AB  - OBJECTIVE: To evaluate the components of canine whole blood samples that
      contribute to results of thromboelastometry (TEM). ANIMALS: 127 healthy dogs.
      PROCEDURES: For each dog, a blood sample was collected from a jugular vein into
      tubes containing no anticoagulant, EDTA, or citrate anticoagulant. Citrated whole
      blood samples underwent TEM with tissue factor and TEM with ellagic acid.
      Indicators of RBC mass and platelet concentration were evaluated, and plasma
      coagulation tests were performed; data obtained were compared with results of
      TEM. For technical reasons, samples were not available from all dogs for all
      tests. RESULTS: Coagulation time was correlated with concentrations of primarily
      extrinsic pathway coagulation factors for TEM with tissue factor and with most
      factors via TEM with ellagic acid. Clot formation time, alpha angle, and maximum
      clot firmness were highly correlated with fibrinogen and platelet concentrations
      and some individual factor concentrations. Sample Hct was strongly correlated
      with most measured variables; low Hct was associated with relative
      hypercoagulability, and high Hct was associated with relative hypocoagulability.
      CONCLUSIONS AND CLINICAL RELEVANCE: For TEM of canine blood samples, coagulation
      time was primarily a function of coagulation factor concentrations, whereas other
      variables were dependent on platelet and fibrinogen concentrations. Sample Hct
      strongly influenced the results of TEM, likely because RBCs act as a diluent for
      plasma coagulation factors. Thromboelastometry appeared to be affected by
      abnormalities of coagulation factors, platelet concentrations, and RBC mass. In
      samples from anemic patients, results of TEM indicative of hypercoagulability may
      be artifactual because of low RBC mass.

PMID- 22620693
TI  - Cardiorespiratory, gastrointestinal, and analgesic effects of morphine sulfate in
      conscious healthy horses.
AB  - OBJECTIVE: To compare the cardiorespiratory, gastrointestinal, analgesic, and
      behavioral effects between IV and IM administration of morphine in conscious
      horses with no signs of pain. ANIMALS: 6 healthy adult horses. PROCEDURES: Horses
      received saline (0.9% NaCl) solution (IM or IV) or morphine sulfate (0.05 and 0.1
      mg/kg, IM or IV) in a randomized, masked crossover study design. The following
      variables were measured before and for 360 minutes after drug administration:
      heart and respiratory rates; systolic, diastolic, and mean arterial blood
      pressures; rectal temperature; arterial pH and blood gas variables; intestinal
      motility; and response to thermal and electrical noxious stimuli. Adverse effects
      and horse behavior were also recorded. Plasma concentrations of morphine,
      morphine-3-glucuronide, and morphine-6-glucuronide were measured via liquid
      chromatography-mass spectrometry. RESULTS: No significant differences in any
      variable were evident after saline solution administration. Intravenous and IM
      administration of morphine resulted in minimal and short-term cardiorespiratory,
      intestinal motility, and behavioral changes. A decrease in gastrointestinal
      motility was detected 1 to 2 hours after IM administration of morphine at doses
      of 0.05 and 0.1 mg/kg and after IV administration of morphine at a dose of 0.1
      mg/kg. Morphine administration yielded no change in any horse's response to
      noxious stimuli. Both morphine-3-glucuronide and morphine-6-glucuronide were
      detected in plasma after IV and IM administration of morphine. CONCLUSIONS AND
      CLINICAL RELEVANCE: Clinically relevant doses of morphine sulfate yielded minimal
      and short-term behavioral and intestinal motility effects in healthy horses with
      no signs of pain. Neither dose of morphine affected their response to a noxious
      stimulus.

PMID- 22620694
TI  - Cardiac adaptive mechanisms of Tibetan antelope (Pantholops hodgsonii) at high
      altitudes.
AB  - OBJECTIVE: To identify cardiac mechanisms that contribute to adaptation to high
      altitudes in Tibetan antelope (Pantholops hodgsonii). ANIMALS: 9 male Tibetan
      antelope and 10 male Tibetan sheep (Ovis aries). PROCEDURES: Tibetan antelope and
      Tibetan sheep inhabiting a region with an altitude of 4,300 m were captured, and
      several cardiac variables were measured. Expression of genes for atrial
      natriuretic peptide, brain natriuretic peptide, and calcium-calmodulin-dependent
      protein kinase II delta was measured via real-time PCR assay. RESULTS: Ratios of
      heart weight to body weight for Tibetan antelope were significantly greater than
      those of Tibetan sheep, but ratios of right-left ventricular weights were
      similar. Mean +/- SD baseline heart rate (26.33 +/- 6.15 beats/min) and systolic
      arterial blood pressure (97.75 +/- 9.56 mm Hg) of antelope were significantly
      lower than those of sheep (34.20 +/- 6.57 beats/min and 130.06 +/- 17.79 mm Hg,
      respectively). The maximum rate of rise in ventricular pressure in antelope was
      similar to that in Tibetan sheep, but after exposure to air providing a fraction
      of inspired oxygen of 14.6% or 12.5% (ie, hypoxic conditions), the maximum rate
      of rise in ventricular pressure of the antelope increased significantly to 145.1%
      or 148.1%, respectively, whereas that of the sheep decreased to 68.4% or 70.5%,
      respectively. Gene expression of calcium-calmodulin-dependent protein kinase II
      delta and atrial natriuretic peptide, but not brain natriuretic peptide, in the
      left ventricle of the heart was significantly higher in antelope than in sheep.
      CONCLUSIONS AND CLINICAL RELEVANCE: Hearts of the Tibetan antelope in this study
      were well adapted to high-altitude hypoxia as shown by higher heart weight
      ratios, cardiac contractility in hypoxic conditions, and expression of key genes
      regulating cardiac contractility and cardiac hypertrophy, compared with values
      for Tibetan sheep.

PMID- 22620695
TI  - Evaluation of the biliary and brain distribution of technetium Tc 99m sestamibi
      in healthy dogs with the ABCB1 wildtype genotype before and after treatment with
      spinosad.
AB  - OBJECTIVE: To determine whether the reported drug-drug interaction between the
      flea medication spinosad and ivermectin is attributable to inhibition of P
      glycoprotein by spinosad. ANIMALS: 6 healthy adult dogs with the ABCB1 wildtype
      genotype. PROCEDURES: The study was conducted as a prospective, masked,
      randomized crossover design. Six dogs were allocated to 2 groups; each dog served
      as its own control animal. Dogs in one of the groups received spinosad at the
      manufacturer's recommended dose; the other group received no treatment. Forty
      eight hours later, scintigraphic imaging of the head and abdomen were performed
      with the radiolabeled P-glycoprotein substrate methoxy-isobutyl-isonitrile
      (sestamibi) in both groups of dogs. After a washout period of 60 days, the dogs
      in each group received the alternate treatment, and scintigraphic imaging again
      was performed 48 hours later. Gallbladder-to-liver and brain-to-neck musculature
      ratios of technetium Tc 99m sestamibi were calculated for each dog and compared
      between treatments. RESULTS: No significant differences in gallbladder-to-liver
      or brain-to-neck musculature ratios were found between treatments. CONCLUSIONS
      AND CLINICAL RELEVANCE: Results provided evidence that spinosad did not inhibit P
      glycoprotein function 48 hours after spinosad was administered at the
      manufacturer's recommended dose. Further investigations will be necessary to
      elucidate the mechanism of the reported toxic interaction between spinosad and
      ivermectin.

PMID- 22620696
TI  - Analysis of clinical and ultrasonographic data by use of logistic regression
      models for prediction of malignant versus benign causes of ultrasonographically
      detected focal liver lesions in dogs.
AB  - OBJECTIVE: To investigate the value of clinical, laboratory, and imaging data for
      use in predicting malignant or benign histologic results for ultrasonographically
      detected focal liver lesions in dogs. SAMPLE: Records and archived images of 247
      dogs evaluated at the University of Minnesota Veterinary Medical Center from 2005
      to 2008 that underwent abdominal ultrasonography and histologic evaluation of the
      liver. PROCEDURES: Data were analyzed with multivariable logistic regression
      models. All dogs were classified as having benign or malignant liver disease on
      the basis of histologic reports. Three multivariable logistic regression models
      were fit to a development subset of the data by use of combinations of
      signalment, historical, physical examination, laboratory, and diagnostic imaging
      (survey radiography and abdominal ultrasonography) data as predictor variables.
      The resulting models were validated by evaluating predictive performance against
      a holdout validation subset of the data. RESULTS: Models that included
      ultrasonographic variables had the highest overall predictive value. In these
      models, greater lesion size and the presence of peritoneal fluid were the only
      variables that had a positive association with malignant liver disease.
      CONCLUSIONS AND CLINICAL RELEVANCE: Large ultrasonographically detected liver
      lesions and the presence of peritoneal fluid were associated with malignant liver
      disease in dogs.

PMID- 22620697
TI  - Evaluation of the correlation between serum biochemical values and liver
      ultrasonographic indices in periparturient cows with different body condition
      scores.
AB  - OBJECTIVE: To determine alterations of serum biochemical variables in relation to
      changes of near- and far-field mean grayscale histogram (MGSH) and attenuation
      rates in liver ultrasonograms of periparturient cows. ANIMALS: 67 Holstein cows.
      PROCEDURES: Cows were allocated on the basis of body condition score into
      underconditioned (n = 21), moderately conditioned (23), and overconditioned (23)
      groups. Serum samples (obtained every 10 days from 30 days before to 30 days
      after calving) were analyzed for aspartate aminotransferase, alanine
      aminotransferase, and gamma-glutamyltransferase activities and BUN, albumin,
      calcium, and inorganic phosphorus concentrations along with digital estimation of
      near- and far-field MGSH values of liver ultrasonograms and deep attenuation.
      Values were compared among groups and within each group, and their correlations
      were determined in the pre- and postpartum periods. RESULTS: Serum biochemical
      variables did not differ significantly among groups. Aspartate aminotransferase
      and gamma-glutamyltransferase activities increased in the postpartum period.
      Fluctuations of alanine aminotransferase activity were not significant; BUN
      decreased significantly in the peripartum period. Albumin concentration decreased
      prior to parturition and remained low, but significantly increased after
      parturition. Calcium concentration decreased on day 10 but subsequently
      increased. Phosphorus concentration decreased stepwise until day 10 after
      calving. Postpartum biochemical variables had weak correlations with near- and
      far-field MGSH values in overconditioned cows. The highest levels of sound
      attenuation were found in overconditioned cows on calving day. CONCLUSIONS AND
      CLINICAL RELEVANCE: Liver ultrasonographic features were poorly correlated with
      changes of serum biochemical variables. This suggests that liver ultrasonography
      is not a good technique for estimating functional liver abnormalities in
      periparturient cows.

PMID- 22620698
TI  - Housing- and exercise-related risk factors associated with the development of hip
      dysplasia as determined by radiographic evaluation in a prospective cohort of
      Newfoundlands, Labrador Retrievers, Leonbergers, and Irish Wolfhounds in Norway.
AB  - OBJECTIVE: To identify housing- and exercise-related risk factors associated with
      the development of hip dysplasia (HD) as determined by radiographic evaluation in
      Newfoundlands, Labrador Retrievers, Leonbergers, and Irish Wolfhounds in Norway.
      ANIMALS: 501 client-owned dogs from 103 litters. PROCEDURES: Dogs were assessed
      from birth until official radiographic screening for HD at 12 (Labrador Retriever
      [n = 133] and Irish Wolfhound [63]) or 18 (Newfoundland [125] and Leonberger
      [180]) months of age. Information regarding housing and exercise conditions
      during the preweaning and postweaning periods was obtained with questionnaires.
      Multivariable random effects logistic regression models were used to identify
      housing- and exercise-related risk factors associated with the development of
      radiographically detectable HD. RESULTS: Puppies walking on stairs from birth to
      3 months of age had an increased risk of developing HD. Factors associated with a
      decreased risk of developing HD included off-leash exercise from birth to 3
      months of age, birth during the spring and summer, and birth on a farm.
      Significant clustering of dogs with HD was detected within litters. CONCLUSIONS
      AND CLINICAL RELEVANCE: Results indicated that puppies <= 3 months old should not
      be allowed access to stairs, but should be allowed outdoor exercise on soft
      ground in moderately rough terrain to decrease the risk for developing
      radiographically detectable HD. These findings could be used as practical
      recommendations for the prevention of HD in Newfoundlands, Labrador Retrievers,
      Leonbergers, and Irish Wolfhounds.

PMID- 22620699
TI  - Detection of interferon-gamma response to tuberculosis in blood collected at
      commencement of exsanguination at slaughter from cattle sensitized with
      Mycobacterium bovis.
AB  - OBJECTIVE: To determine whether an interferon (IFN)-gamma response sufficient to
      categorize cattle as positive for tuberculosis can be detected in blood collected
      at commencement of exsanguination at slaughter. ANIMALS: 15 Holstein cows.
      PROCEDURES: 12 cows were experimentally sensitized by SC injection with
      inactivated Mycobacterium bovis in mineral oil, which induced an immune response
      that mimicked natural infection with M bovis. Three nonsensitized control cows
      were injected SC with mineral oil alone. By 5 weeks after injection, only the 12
      sensitized cows had positive results for tuberculosis with whole blood IFN-gamma
      assay. At that time, all 15 cows were sent to slaughter and samples of blood were
      collected from each cow immediately before stunning and at commencement of
      exsanguination (within 90 seconds after stunning). A whole blood IFN-gamma assay
      was performed on the samples. Conditional probability and paired t tests were
      used to analyze changes in the categorical test interpretation and qualitative
      IFN-gamma production, respectively. RESULTS: All 12 sensitized cows had positive
      results for tuberculosis in samples obtained immediately before stunning, and 9
      retained positive results for samples obtained at commencement of exsanguination.
      There was a significant decrease in the mean background-corrected IFN-gamma ELISA
      optical density values for samples obtained at commencement of exsanguination.
      CONCLUSIONS AND CLINICAL RELEVANCE: IFN-gamma response sufficient to classify
      cattle as positive for tuberculosis could be detected in blood collected at
      commencement of exsanguination. These findings support further development and
      use of the IFN-gamma assay on blood samples collected at exsanguination as part
      of a bovine tuberculosis surveillance program.

PMID- 22620700
TI  - Detection of heartworm infection in dogs via PCR amplification and electrospray
      ionization mass spectrometry of nucleic acid extracts from whole blood samples.
AB  - OBJECTIVE: To develop and evaluate a rapid and accurate assay involving PCR
      amplification and electrospray ionization mass spectrometry of nucleic acid
      extracts from whole blood samples for the detection of Dirofilaria immitis
      infection in dogs. SAMPLE: Whole blood nucleic acid extracts from 29 dogs
      experimentally infected with D immitis (and in which circulating D immitis
      antigen was detected) and 10 uninfected dogs. PROCEDURES: 16 of the 29 whole
      blood samples from infected dogs were examined at the time of collection for
      circulating microfilaria. Nucleic acids were extracted from all whole blood
      specimens and underwent PCR amplification with 12 PCR primer pairs designed to
      detect a wide range of pathogens (including the Wolbachia endosymbiont of D
      immitis) and electrospray ionization mass spectrometry. RESULTS: On the basis of
      assay results, heartworm infection was detected in 13 of 13 antigen-positive dogs
      of unknown microfilaria status, 11 of 11 antigen-positive dogs with circulating
      microfilaria, 0 of 3 antigen-positive dogs tested at 3 months after larval
      infection, 0 of 2 antigen-positive dogs with occult infections, and 0 of 10
      uninfected dogs. CONCLUSIONS AND CLINICAL RELEVANCE: With the assay under
      investigation, it was possible to identify D immitis infection in dogs with
      circulating microfilaria via detection of the obligate Wolbachia endosymbiont of
      D immitis. It was not possible to identify dogs with occult infections, which
      suggested that circulating microfilaria must be present to detect infection with
      this assay, although further studies would be required to verify that finding.

PMID- 22620701
TI  - Measurement of digital laminar and venous temperatures as a means of comparing
      three methods of topically applied cold treatment for digits of horses.
AB  - OBJECTIVE: To compare effects of 3 methods of topically applied cold treatment
      (cryotherapy) on digital laminar and venous temperatures in horses. ANIMALS: 9
      healthy adult Thoroughbreds. PROCEDURES: Thermocouples were placed in palmar
      digital veins and digital laminae of both forelimbs of horses. Three methods of
      cryotherapy were applied to the distal aspects of the limbs: wader boot (63-cm
      tall vinyl boot filled with ice and water [ice slurry]), ice bag (5-L fluid bag
      filled with ice slurry), and a gel pack boot (boot containing frozen gel packs).
      Gel packs and ice slurries were replenished every hour during cryotherapy. The
      forelimb that received the first treatment was randomly assigned; thereafter,
      control and treated forelimbs were alternated for each treatment. For each
      treatment, temperatures were recorded every minute during 15-minute pretreatment,
      2-hour treatment, and >= 30 minute rewarming periods. Once temperatures had
      returned to within 3 degrees C below pretreatment values, the experiment was
      repeated in a similar manner for other cryotherapy methods. RESULTS: Digital
      venous temperatures were similar to laminar temperatures during each treatment.
      Ice bag and wader boot treatments caused similar cooling of digits. Gel boot
      treatment did not cause substantial cooling of digits. CONCLUSIONS AND CLINICAL
      RELEVANCE: Ice bag treatment caused laminar and digital venous cooling equivalent
      to that of wader boot treatment. Cryotherapy by use of 5-L fluid bags with an ice
      slurry may be a readily available, practical, and efficient method for prevention
      of laminitis in horses. Digital laminar and venous temperatures were similar in
      forelimbs of horses before and during cryotherapy.

PMID- 22620702
TI  - Effect of repeated oral administration of glucose and leucine immediately after
      exercise on plasma insulin concentration and glycogen synthesis in horses.
AB  - OBJECTIVE: To determine whether repeated oral administration of glucose and
      leucine during the period immediately after intense exercise would increase the
      release of insulin and thereby enhance glycogen synthesis in horses. ANIMALS: 12
      Standardbred horses. PROCEDURES: In a crossover study design, after glycogen
      depleting exercise, horses received oral boluses of glucose (1 g/kg at 0, 2, and
      4 hours) and leucine (0.1 g/kg at 0 and 4 hours) or boluses of water (10 mL/kg at
      0, 2, and 4 hours; control treatment). Blood samples for determination of
      glucose, insulin, and leucine concentrations were collected prior to and during a
      6-hour period immediately after exercise. Biopsy specimens of a gluteus muscle
      were obtained before and immediately after exercise and at 3, 6, and 24 hours
      after exercise for measurement of glycogen concentration. RESULTS: When glucose
      and leucine were administered to the horses, plasma insulin concentration was
      significantly higher during the 6 hours immediately after exercise than it was
      when water was administered to the horses. Serum glucose concentration during the
      4 hours immediately after exercise was significantly higher when glucose and
      leucine were administered than the serum glucose concentration when water was
      administered. Muscle glycogen concentrations did not differ between the 2
      treatments during the 24 hours after exercise. CONCLUSIONS AND CLINICAL
      RELEVANCE: Synthesis of muscle glycogen after intense intermittent exercise was
      not enhanced by oral boluses of glucose and leucine after exercise despite
      pronounced increases in plasma insulin and serum glucose concentrations.

PMID- 22620703
TI  - Effects of clenbuterol administration on serum biochemical, histologic, and
      echocardiographic measurements of muscle injury in exercising horses.
AB  - OBJECTIVE: To determine the effects of clenbuterol, at a dosage of up to 3.2
      MUg/kg for 14 days, PO, on skeletal and cardiac muscle in healthy horses
      undergoing treadmill exercise. ANIMALS: 12 healthy horses from 3 to 10 years old.
      PROCEDURES: Horses were randomly assigned to a control group (n = 6) or
      clenbuterol group (6) and received either saline (0.9% NaCl) solution or
      clenbuterol, PO, every 12 hours for 14 days. Horses were subjected to submaximal
      treadmill exercise daily during treatment. Muscle biopsy specimens were collected
      before and after treatment for determination of apoptosis. Echocardiographic
      measurements, serum clenbuterol and cardiac troponin I concentrations, and serum
      activities of creatine kinase and aspartate aminotransferase were measured
      before, during, and after treatment. Jugular venous blood samples were collected
      every 3 days during treatment. Echocardiography was repeated every 7 days after
      beginning treatment. Response variables were compared between treatment groups
      and across time periods. RESULTS: No significant effect of clenbuterol or
      exercise on response variables was found between treatment and control groups at
      any time point or within groups over time. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results did not reveal any adverse effects of treatment with an approved dose of
      clenbuterol on equine cardiac or skeletal muscle in the small number of horses
      tested.

PMID- 22620704
TI  - Flow cytometric evaluation of peripheral blood and bone marrow and fine-needle
      aspirate samples from multiple sites in dogs with multicentric lymphoma.
AB  - OBJECTIVE: To determine whether the extent of disease in dogs with lymphoma can
      be assessed via flow cytometry and to evaluate the suitability of fine-needle
      aspirates from the liver and spleen of dogs for flow cytometric examination.
      ANIMALS: 44 dogs with multicentric B-cell (n = 35) or T-cell lymphoma (9) and 5
      healthy control dogs. Procedures-Peripheral blood and bone marrow samples and
      fine-needle aspirates of lymph node, liver, and spleen were examined via flow
      cytometry. Logarithmically transformed T-cell-to-B-cell percentage ratio
      (log[T:B]) values were calculated. Thresholds defined by use of log(T:B) values
      of samples from control dogs were used to determine extranodal lymphoma
      involvement in lymphoma-affected dogs; results were compared with cytologic
      findings. RESULTS: 12 of 245 (5%) samples (9 liver, 1 spleen, and 2 bone marrow)
      had insufficient cellularity for flow cytometric evaluation. Mean log(T:B) values
      of samples from dogs with B-cell lymphoma were significantly lower than those of
      samples from the same site in dogs with T-cell lymphoma and in control dogs. In
      dogs with T-cell lymphoma, the log(T:B) of lymph node, bone marrow, and spleen
      samples was significantly higher than in control dogs. Of 165 samples assessed
      for extranodal lymphoma involvement, 116 (70%) tested positive via flow
      cytometric analysis; results agreed with cytologic findings in 133 of 161 (83%)
      samples evaluated via both methods. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      suggested that flow cytometry may aid in detection of extranodal lymphoma
      involvement in dogs, but further research is needed. Most fine-needle aspirates
      of liver and spleen were suitable for flow cytometric evaluation.

PMID- 22620705
TI  - Use of recombinant human granulocyte colony-stimulating factor prior to
      autologous bone marrow transplantation in dogs with lymphoma.
AB  - OBJECTIVE: To retrospectively assess the safety and efficacy of recombinant human
      granulocyte colony-stimulating factor (G-CSF) used as part of autologous bone
      marrow transplantation in dogs with lymphoma. ANIMALS: 21 dogs with lymphoma at
      any disease stage. PROCEDURES: Medical records of dogs with lymphoma that
      underwent intensified chemotherapy and received an autologous bone marrow
      transplant following owner administration of recombinant human G-CSF (5 MUg/kg,
      SC, q 12 h) for 7 days between January 2007 and July 2009 were reviewed. Results
      of physical examinations and CBCs performed before and at intervals during a 24
      month period after G-CSF treatment were assessed. The safety of recombinant human
      G-CSF administration was determined via assessment of both short-term (ie, during
      the 7-day G-CSF treatment period) and long-term adverse effects. RESULTS: None of
      the dogs developed any adverse effect attributable to the administration of
      recombinant human G-CSF during G-CSF administration or during follow-up periods
      of 1 month to 2 years (median follow-up period, 4 months). Among the 18 dogs for
      which CBC results were available for analysis, mean circulating neutrophil count
      significantly increased after administration of recombinant human G-CSF, compared
      with value before treatment. CONCLUSIONS AND CLINICAL RELEVANCE- Results
      indicated that recombinant human G-CSF administered SC at a dosage of 5 MUg/kg
      every 12 hours for 7 days appeared to be safe and effective when used in dogs
      with lymphoma that were undergoing autologous bone marrow transplant.

PMID- 22620706
TI  - Influence of P-glycoprotein modulation on plasma concentrations and
      pharmacokinetics of orally administered prednisolone in dogs.
AB  - OBJECTIVE: To evaluate the impact of modulation of the membrane-bound efflux pump
      P-glycoprotein (P-gp) on plasma concentrations of orally administered
      prednisolone in dogs. ANIMALS: 7 healthy adult Beagles. PROCEDURES: Each dog
      received 3 treatments (control [no treatment], rifampicin [100 mg/d, PO, for 21
      days, as an inducer of P-gp], and ketoconazole [100 mg/d, PO, for 21 days, as an
      inhibitor of P-gp]). A single dose of prednisolone (1 mg/kg, PO) was administered
      on day 8 of each treatment period. There was a 7-day washout period between
      subsequent treatments. Plasma concentrations of prednisolone were determined by
      use of a validated liquid chromatography-tandem mass spectrometry method.
      Duodenum and colon biopsy specimens were obtained endoscopically from
      anesthetized dogs and assessed for P-gp protein labeling via immunohistochemical
      analysis and mRNA quantification via real-time PCR assay. Total fecal collection
      was performed for evaluation of effects of P-gp modulation on digestion of
      nutrients. RESULTS: Rifampicin treatment upregulated duodenal P-gp in dogs and
      significantly reduced the area under the plasma concentration-time curve of
      prednisolone. Ketoconazole typically downregulated expression of duodenal P-gp,
      with a subsequent increase in the area under the plasma concentration-time curve
      of prednisolone. There was a noticeable interindividual difference in response.
      Digestion of nutrients was not affected. CONCLUSIONS AND CLINICAL RELEVANCE:
      Modulation of P-gp expression influenced plasma concentrations of prednisolone
      after oral administration in dogs. Thus, treatment response to prednisolone may
      be influenced by coadministration of P-gp-modulating medications or feed
      ingredients.

PMID- 22620707
TI  - Cardiovascular and respiratory effects of incremental doses of dopamine and
      phenylephrine in the management of isoflurane-induced hypotension in cats with
      hypertrophic cardiomyopathy.
AB  - OBJECTIVE: To determine cardiopulmonary effects of incremental doses of dopamine
      and phenylephrine during isoflurane-induced hypotension in cats with hypertrophic
      cardiomyopathy (HCM). ANIMALS: 6 adult cats with severe naturally occurring HCM.
      PROCEDURES: Each cat was anesthetized twice (once for dopamine treatment and once
      for phenylephrine treatment; treatment order was randomized). Hypotension was
      induced by increasing isoflurane concentration. Cardiopulmonary data, including
      measurement of plasma concentration of cardiac troponin I (cTnI), were obtained
      before anesthesia, 20 minutes after onset of hypotension, and 20 minutes after
      each incremental infusion of dopamine (2.5, 5, and 10 MUg/kg/min) or
      phenylephrine (0.25, 0.5, and 1 MUg/kg/min). RESULTS: Mean +/- SD end-tidal
      isoflurane concentration for dopamine and phenylephrine was 2.44 +/- 0.05% and
      2.48 +/- 0.04%, respectively. Cardiac index and tissue oxygen delivery were
      significantly increased after administration of dopamine, compared with results
      after administration of phenylephrine. Systemic vascular resistance index was
      significantly increased after administration of phenylephrine, compared with
      results after administration of dopamine. Oxygen consumption remained unchanged
      for both treatments. Systemic and pulmonary arterial blood pressures were
      increased after administration of both dopamine and phenylephrine. Acid-base
      status and blood lactate concentration did not change and were not different
      between treatments. The cTnI concentration increased during anesthesia and
      infusion of dopamine and phenylephrine but did not differ significantly between
      treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Dopamine and phenylephrine
      induced dose-dependent increases in systemic and pulmonary blood pressure, but
      only dopamine resulted in increased cardiac output. Hypotension and infusions of
      dopamine and phenylephrine caused significant increases in cTnI concentrations.

PMID- 22620708
TI  - Effects of unilateral arytenoid lateralization technique and suture tension on
      airway pressure in the larynx of canine cadavers.
AB  - OBJECTIVE: To evaluate effects of the arytenoid lateralization technique and
      suture tension on airway pressure in the canine larynx. SAMPLE: 7 canine cadaver
      larynges. PROCEDURES: Negative pressure was elicited aboral to the larynx. Airway
      pressure was measured at airflows of 15 to 120 L/min before and after
      thyroarytenoid lateralization (TAL), cricoarytenoid lateralization (CAL), and
      combined TAL and CAL (cricothyroarytenoid lateralization [CTAL]) at 100 and 500 g
      of suture tension and with sectioning of the sesamoid cartilage (SSC) and
      disarticulation of the cricothyroid joint (DCTJ). Rima glottidis area (RGA) was
      measured. Effects of technique, modification, and suture tension on pressure and
      RGA were evaluated statistically. RESULTS: Increased suture tension significantly
      reduced airway pressure for TAL at 30 L/min, CAL at 45 to 120 L/min, and CAL
      after SSC and DCTJ at 60, 75, and 105 to 120 L/min. The CAL and CTAL caused
      significantly lower airway pressures than did TAL > 30 L/min, but SSC and DCTJ
      did not significantly reduce pressure. All procedures, except TAL at 100 g of
      tension, resulted in a significant RGA increase from baseline. The CAL and CTAL
      caused a significantly greater RGA than did TAL. For TAL at 100 g of tension, SSC
      significantly increased RGA. CONCLUSIONS AND CLINICAL RELEVANCE: CAL and CTAL
      caused lower airway pressures than did TAL. No significant pressure differences
      were detected between CAL and CTAL; SSC and DCTJ had little effect on pressure.
      Pressure may be a more sensitive indicator of airflow than is RGA in the larynx
      of canine cadavers.

PMID- 22620710
TI  - Aromaticity of overcrowded nitroanilines.
AB  - For a series of 2,4,6-trinitroanilines substituted with bulky groups, the
      influence of intramolecular hydrogen bonds, electronic substituents effect, and
      steric hindrance on aromaticity of the molecules in crystals and their analogues
      optimized at the B3LYP/6-311++G** level were studied. The HOMA index was used as
      a measure of the aromaticity, while the parameter DeltaP was a description of the
      distortion of the benzene ring from planarity. Conformation of the nonplanar ring
      in crystal and optimized structures was also described using the puckering
      parameters. A comparison of the data for crystal and optimized structures showed
      an important effect of the intermolecular interactions on aromaticity of the
      overcrowded nitroanilines. The packing effects were analyzed using the simplified
      PCM model of solvents. NBO analysis illustrated the changes of orbitals upon
      dearomatisation.

PMID- 22620709
TI  - Osmotic coefficients of aqueous weak electrolyte solutions: influence of
      dissociation on data reduction and modeling.
AB  - The experimental determination and modeling of osmotic coefficients in
      electrolyte solutions requires knowledge of the stoichiometric coefficient nu(i).
      In contrast to strong electrolytes, weak electrolytes exhibit a concentration
      dependent stoichiometric coefficient, which directly influences the thermodynamic
      properties (e.g., osmotic coefficients). Neglecting this concentration dependence
      leads to erroneous osmotic coefficients for solutions of weak electrolytes. In
      this work, the concentration dependence of the stoichiometric coefficients and
      the influence of concentration on the osmotic coefficient data were accounted for
      by considering the dissociation equilibria of aqueous sulfuric and phosphoric
      acid systems. The dissociation equilibrium was combined with the ePC-SAFT
      equation of state to model osmotic coefficients and densities of electrolyte
      solutions. Without the introduction of any additional adjustable parameters, the
      average relative deviation between the modeled and the experimental data
      decreases from 12.82% to 4.28% (osmotic coefficients) and from 2.59% to 0.89%
      (densities) for 12 phosphoric and sulfuric systems compared to calculations that
      do not account for speciation. For easy access to the concentration-dependent
      stoichiometric coefficient, estimation schemes were formulated for mono-, di-,
      and triprotic acids and their salts.

PMID- 22620711
TI  - Commentary on the supplement american journal of obstetrics and gynecology: a
      hormonal contraceptive update: a decade of innovation and transformation.

PMID- 22620712
TI  - Aspects on the integrative actions of the brain from neural networks to "brain
      body medicine".
AB  - "Integration" is a key term in describing how nervous system can perform high
      level functions. A first condition to have "integration" is obviously the
      presence of efficient "communication processes" among the parts that have to be
      combined into the harmonious whole. In this respect, two types of communication
      processes, called wiring transmission (WT) and volume transmission (VT),
      respectively, were found to play a major role in the nervous system, allowing the
      exchange of signals not only between neurons, but rather among all cell types
      present in the central nervous system (CNS). A second fundamental aspect of a
      communication process is obviously the recognition/decoding process at target
      level. As far as this point is concerned, increasing evidence emphasizes the
      importance of supramolecular complexes of receptors (the so called receptor
      mosaics) generated by direct receptor-receptor interactions. Their assemblage
      would allow a first integration of the incoming information already at the plasma
      membrane level. Recently, evidence of two new subtypes of WT and VT has been
      obtained, namely the tunnelling nanotubes mediated WT and the microvesicle (in
      particular exosomes) mediated VT allowing the horizontal transfer of bioactive
      molecules, including receptors, RNAs and micro-RNAs. The physiological and
      pathological implications of these types of communication have opened up a new
      field that is largely still unexplored. In fact, likely unsuspected integrative
      actions of the nervous system could occur. In this context, a holistic approach
      to the brain-body complex as an indissoluble system has been proposed. Thus, the
      hypothesis has been introduced on the existence of a brain-body integrative
      structure formed by the "area postrema/nucleus tractus solitarius" (AP/NTS) and
      the "anteroventral third ventricle region/basal hypothalamus with the median
      eminence" (AV3V-BH). These highly interconnected regions operate as specialized
      interfaces between the brain and the body integrating brain-borne and body-borne
      neural and humoral signals.

PMID- 22620713
TI  - Tuberculin reactivity in first-year schoolchildren in Madagascar.
AB  - OBJECTIVE: The tuberculin skin test (TST) is an important tool in the diagnosis
      of tuberculosis infection in children. However, the interpretation of TST may be
      complicated by prior Bacillus Calmette-Guerin (BCG) vaccination. We evaluated the
      effect of vaccination with BCG on TST reactivity in first-year pupils attending
      state schools in Antananarivo. METHODS: STs were performed on 376 first-year
      schoolchildren, aged 6 and 7, attending two state primary schools. The
      relationships between epidemiological information, BCG status (vaccination, BCG
      scars) and TST reactivity were assessed to compare TST sensitivity between
      children with and without BCG vaccination and between those with and without a
      BCG scar. RESULT: The prevalence of positive TST results of >=5, >=10 and >= 15
      mm was 20.2% (76/376), 18.3% (69/376) and 11.4% (43/376), respectively. BCG
      vaccination was not associated with TST reactivity, whatever the threshold used:
      >=5 mm (odds ratio (OR, 1.2; 95% confidence interval (CI), 0.7-2.0); >=10 mm (OR,
      0.9; 95% CI, 0.6-1.7); >=15 mm (OR, 0.6; 95% CI, 0.3-1.2). CONCLUSION: These
      results suggest that in Madagascar, a positive TST result indicates TB infection
      (active or latent) rather than past BCG vaccination. Therefore, high BCG
      vaccination coverage does not appear to impair the usefulness of the TST as a
      tool for diagnosing tuberculosis.

PMID- 22620714
TI  - Nonclassical beta-hydrogen elimination of hydrosilazido zirconium compounds via
      direct hydrogen transfer.
AB  - Salt metathesis reactions of Cp(2)(NR(2))ZrX (X = Cl, I, OTf) and lithium
      hydrosilazides ultimately afford hydride products Cp(2)(NR(2))ZrH that suggest
      unusual beta-hydrogen elimination processes. A likely intermediate in one of
      these reactions, Cp(2)Zr[N(SiHMe(2))t-Bu][N(SiHMe(2))(2)], is isolated under
      controlled synthetic conditions. Addition of alkali metal salts to this zirconium
      hydrosilazide compound produces the corresponding zirconium hydride. However as
      conditions are varied, a number of other pathways are also accessible, including
      C-H/Si-H dehydrocoupling, gamma-abstraction of a CH, and beta-abstraction of a
      SiH. Our observations suggest that the conversion of (hydrosilazido)zirconocene
      to zirconium hydride and silanimine does not follow the classical four-center
      mechanism for beta-elimination.

PMID- 22620715
TI  - Synthesis, structure, magnetic behavior, and theoretical analysis of diazine
      bridged magnetic ladders: Cu(quinoxoline)X2 and Cu(2,3-dimethylpyrazine)X2 (X =
      Cl, Br).
AB  - The synthesis, structure, and magnetic behavior of the complexes Cu(qnx)Br(2)
      (1), Cu(2,3-dmpz)Br(2) (2), Cu(qnx)Cl(2) (3), and Cu(2,3-dmpz)Cl(2) (4) (qnx =
      quinoxaline, dmpz = dimethylpyrazine) are described. Both X-ray structural data
      and fitting of the magnetic data suggest that the compounds are well-described as
      strong-rung, two-leg magnetic ladders with J(rung) ranging from -30 K to -37 K,
      and J(rail) ranging from -14 K to -24 K. An unexpected decrease in the exchange
      constant for J(rail) (through the diazine ligand) is observed when the halide ion
      is changed from bromide to chloride, along with a small decrease in the magnetic
      exchange through the halide ion. Theoretical calculations on 2 and 4 via a first
      principles bottom-up approach confirmed the description of the complexes as two
      leg magnetic ladders. Furthermore, the calculations provide an explanation for
      the experimentally observed change in the value of the magnetic exchange through
      the dmpz ligand when the halide ion is changed from bromide to chloride, and for
      the very small change observed in the exchange through the different halide ions
      themselves via a combination of changes in geometry, bond lengths, and anion
      volume.

PMID- 22620716
TI  - Blast-induced biomechanical loading of the rat: an experimental and anatomically
      accurate computational blast injury model.
AB  - Blast waves generated by improvised explosive devices (IEDs) cause traumatic
      brain injury (TBI) in soldiers and civilians. In vivo animal models that use
      shock tubes are extensively used in laboratories to simulate field conditions, to
      identify mechanisms of injury, and to develop injury thresholds. In this article,
      we place rats in different locations along the length of the shock tube (i.e.,
      inside, outside, and near the exit), to examine the role of animal placement
      location (APL) in the biomechanical load experienced by the animal. We found that
      the biomechanical load on the brain and internal organs in the thoracic cavity
      (lungs and heart) varied significantly depending on the APL. When the specimen is
      positioned outside, organs in the thoracic cavity experience a higher pressure
      for a longer duration, in contrast to APL inside the shock tube. This in turn
      will possibly alter the injury type, severity, and lethality. We found that the
      optimal APL is where the Friedlander waveform is first formed inside the shock
      tube. Once the optimal APL was determined, the effect of the incident blast
      intensity on the surface and intracranial pressure was measured and analyzed.
      Noticeably, surface and intracranial pressure increases linearly with the
      incident peak overpressures, though surface pressures are significantly higher
      than the other two. Further, we developed and validated an anatomically accurate
      finite element model of the rat head. With this model, we determined that the
      main pathway of pressure transmission to the brain was through the skull and not
      through the snout; however, the snout plays a secondary role in diffracting the
      incoming blast wave towards the skull.

PMID- 22620717
TI  - Treatment of reticular and telangiectatic leg veins: double-blind, prospective
      comparative trial of polidocanol and hypertonic saline.
AB  - BACKGROUND: Sixty-three subjects' legs were randomized to receive treatment with
      polidocanol (POL) or hypertonic saline (HS) for telangiectasias and reticular leg
      veins. OBJECTIVE: To compare the safety and efficacy of two sclerosing agents in
      three dermatologic surgery practices. METHODS: After exclusion of saphenofemoral
      junction incompetence, each subject's veins were categorized (telangiectasias <1
      mm and reticular veins 1-3 mm) and randomized. Telangiectasias were treated with
      POL 0.5% or 11.7% HS and reticular veins with POL 1% or 23.4% HS. An independent,
      blinded physician determined efficacy and adverse events. Subject satisfaction
      questionnaires were administered and global clinical improvement assessments
      performed. RESULTS: All patients completed four visits at 0, 1, 4, and 12 weeks.
      Patients reported significantly greater pain during treatment with HS (2.42) than
      POL (1.03) (p < .001). There were no significant differences in physician
      assessed improvement of reticular leg veins or telangiectasias; subject- or
      physician-assessed overall improvement; or physician-assessed phlebitis,
      pigmentation, edema, or matting in either of the three practices or the entire
      cohort. Two subjects developed ulcerations with HS. No ulcerations or allergic
      reactions developed after POL injections. CONCLUSION: Both agents provided
      effective treatment, but HS caused 2.35 times as much pain during injections and
      resulted in two episodes of tissue necrosis.

PMID- 22620850
TI  - Synthesis and optical properties of small Au nanorods using a seedless growth
      technique.
AB  - Gold nanoparticles have shown potential in photothermal cancer therapy and
      optoelectronic technology. In both applications, a call for small size nanorods
      is warranted. In the present work, a one-pot seedless synthetic technique has
      been developed to prepare relatively small monodisperse gold nanorods with
      average dimensions (length * width) of 18 * 4.5 nm, 25 * 5 nm, 15 * 4.5 nm, and
      10 * 2.5 nm. In this method, the pH was found to play a crucial role in the
      monodispersity of the nanorods when the NaBH(4) concentration of the growth
      solution was adjusted to control the reduction rate of the gold ions. At the
      optimized pH and NaBH(4) concentrations, smaller gold nanorods were produced by
      adjusting the CTAB concentration in the growth solution. In addition, the
      concentration of silver ions in the growth solution was found to be pivotal in
      controlling the aspect ratio of the nanorods. The extinction coefficient values
      for the small gold nanorods synthesized with three different aspect ratios were
      estimated using the absorption spectra, size distributions, and the atomic
      spectroscopic analysis data. The previously accepted relationships between the
      extinction coefficient or the longitudinal band wavelength values and the
      nanorods' aspect ratios found for the large nanorods do not extend to the small
      size domain reported in the present work. The failure of extending these
      relationships over larger sizes is a result of the interaction of light with the
      large rods giving an extinction band which results mostly from scattering
      processes while the extinction of the small nanorods results from absorption
      processes.

PMID- 22620718
TI  - TGF-beta blockade does not improve control of an established persistent viral
      infection.
AB  - Acute resolving viral infections are often associated with a strong and multi
      specific T-cell response, whereas in persistent viral infections T-cell responses
      are often impaired. It has been suggested that the resuscitation of the antiviral
      T-cell response could be a powerful tool to target persisting viruses. Several
      immunoregulatory pathways, such as IL-10 and TGF-beta, have been shown to be
      involved in the induction of T-cell exhaustion and viral persistence. In this
      study, we sought to investigate whether TGF-beta signaling is also relevant in
      the maintenance of T-cell exhaustion after viral persistence has been
      established, and whether blockade of TGF-beta signaling could improve control of
      viral replication in a mouse model of persistent virus infection. Using the LCMV
      clone 13 model, we analyzed the frequency, function, and phenotype of virus
      specific CD4 and CD8 T cells following therapeutic TGF-beta signaling blockade.
      We show that in vivo blockade of the TGF-beta receptor failed to substantially
      enhance the antiviral T-cell response, and was insufficient to mediate a
      therapeutically-relevant reduction of viral titers in different tissues. Thus,
      although TGF-beta signaling has the ability to hamper antiviral immunity, its
      pharmacological blockade may not be sufficient to tackle persistent viruses.

PMID- 22620851
TI  - Alloy formation at the tetrapod core/arm interface.
AB  - The nature of the interfacial structure between the core and the arms of a
      tetrapod quantum dot (QD) formed during the heteroepitaxial growth of a ZnS arm
      onto a CdSe core is not well understood but can be analyzed through the use of
      high-frequency electron paramagnetic resonance (HF-EPR) spectroscopy. The
      spectroscopic resolution at high frequency allows the presence of unique crystal
      fields reflecting interfacial alloying to be analyzed by incorporating Mn(II)
      ions as a dopant into the QD to act as an intentional EPR active spectroscopic
      probe. In addition, the HF-EPR can spectroscopically observe the presence of ion
      vacancies that are anticipated to form at the heteroepitaxial interface to
      accommodate structural mismatch. The HF-EPR spectra for Mn(II) are extremely
      sensitive to perturbations of the microenvironment due to changes in the crystal
      field. The HF-EPR spectra of Mn(II) in a CdSe (core)/ZnS (arm) tetrapod
      exhibiting wurtzite symmetry for both core and interface of the tetrapod provide
      clear evidence of heteroalloying at the core-arm interface and formation of
      intrinsic dislocations at grain boundaries. The formation of the interfacial
      alloy and grain boundaries reflects short-range ion migration at the
      heteroepitaxial layer to reduce strain energy due to the 12% lattice mismatch
      between the wurtzite lattices of CdSe and ZnS.

PMID- 22620852
TI  - Effects of tear hyperosmolarity on conjunctival cells in mild to moderate dry
      eye.
AB  - PURPOSE: To analyze the effects of tear hyperosmolarity on conjunctival cells in
      mild to moderate dry eye. METHODS: Sixty-eight subjects (35 females and 33 males,
      mean age 43, S.D. 20.3, range 18-87 years) with symptoms of dry eye were enrolled
      in the study. Patients with severe dry eye or any other condition that induces
      ocular inflammation were excluded. The sample was divided into two groups
      according to the tear osmolarity cut-off value of 308 mOsmol L(-1) measured in
      the right eye of each patient. Impression cytology of the temporal interpalpebral
      conjunctiva was performed and goblet cell density, nucleus diameter, cytoplasm
      diameter and nucleus/cytoplasm ratio of epithelial cells quantitatively assessed.
      A battery of tear tests (ferning test, tear break-up time and Schirmer I test)
      was also carried out in order to more completely describe the groups and
      understand the process. Analysis of variance (anova) was applied to establish
      cytological and tear differences between hyperosmolar and normal tear osmolarity
      eyes. Pearson's correlation was calculated between the cytological variables and
      tear osmolarity. RESULTS: The normal tear osmolarity group included patients with
      symptoms of dry eye, grade 1-2 of squamous metaplasia, and a number of positive
      tear signs of dry eye ranging between 0 and 3. The hyperosmolar tear group
      included patients with symptoms of dry eye, grade 1-2 of squamous metaplasia with
      significantly lower values of nucleus diameter (F(1,66) = 4.3, p = 0.040), and a
      number of positive tear signs of dry eye ranging between 1 (hyperosmolar tear)
      and 4. Mean reflex secretion of tears was clearly normal in both groups but
      significantly lower (F(1,66) = 7.2, p = 0.009) in the hyperosmolar tear group.
      Significant correlations were established for tear osmolarity and goblet cell
      density (r(33) = 0.45, p = 0.006) and nucleus/cytoplasm ratio (r(33) = -0.44, p =
      0.009) in the normal tear osmolarity group but not in the hyperosmolar tear
      group. CONCLUSIONS: Mild to moderate hyperosmolar tear conditions seem to lead to
      an initial reduction of the conjunctival cell nucleus before the cytoplasm
      diameter showed a clear tendency to enlarge. The relationship between tear
      osmolarity and conjunctival cell characteristics seems to be linear only in the
      normal tear osmolarity group. These results also provide a plausible link between
      lower reflex secretion of tears and hyperosmolarity.

PMID- 22620854
TI  - Analysis and purification of bioactive natural products: the AnaPurNa study.
AB  - Based on a meta-analysis of data mined from almost 2000 publications on bioactive
      natural products (NPs) from >80000 pages of 13 different journals published in
      1998-1999, 2004-2005, and 2009-2010, the aim of this systematic review is to
      provide both a survey of the status quo and a perspective for analytical
      methodology used for isolation and purity assessment of bioactive NPs. The study
      provides numerical measures of the common means of sourcing NPs, the
      chromatographic methodology employed for NP purification, and the role of
      spectroscopy and purity assessment in NP characterization. A link is proposed
      between the observed use of various analytical methodologies, the challenges
      posed by the complexity of metabolomes, and the inescapable residual complexity
      of purified NPs and their biological assessment. The data provide inspiration for
      the development of innovative methods for NP analysis as a means of advancing the
      role of naturally occurring compounds as a viable source of biologically active
      agents with relevance for human health and global benefit.

PMID- 22620855
TI  - Orotidine 5'-monophosphate decarboxylase: transition state stabilization from
      remote protein-phosphodianion interactions.
AB  - Mutants of orotidine 5'-monophosphate decarboxylase containing all possible
      single (Q215A, Y217F, and R235A), double, and triple substitutions of the side
      chains that interact with the phosphodianion group of the substrate orotidine 5'
      monophosphate have been prepared. Essentially the entire effect of these
      mutations on the decarboxylation of the truncated neutral substrate 1-(beta-d
      erythrofuranosyl)orotic acid that lacks a phosphodianion group is expressed as a
      decrease in the third-order rate constant for activation by phosphite dianion.
      The results are consistent with a model in which phosphodianion binding
      interactions are utilized to stabilize a rare closed enzyme form that exhibits a
      high catalytic activity for decarboxylation.

PMID- 22620856
TI  - Genetic diversity and networks of exchange: a combined approach to assess intra
      breed diversity.
AB  - BACKGROUND: Cryopreservation of three endangered Belgian sheep breeds required to
      characterize their intra-breed genetic diversity. It is assumed that the genetic
      structure of a livestock breed depends mostly on gene flow due to exchanges
      between herds. To quantify this relation, molecular data and analyses of the
      exchanges were combined for three endangered Belgian breeds. METHODS: For each
      breed, between 91 and 225 sheep were genotyped with 19 microsatellites. Genetic
      differentiations between breeds and among herds within a breed were evaluated and
      the genetic structure of the breeds was described using Bayesian clustering
      (Structure). Exchanges of animals between 20, 46 and 95 herds according to breed
      were identified via semi-directed interviews and were analyzed using the concepts
      of the network theory to calculate average degrees and shortest path lengths
      between herds. Correlation between the Reynolds' genetic distances and the
      shortest path lengths between each pair of herds was assessed by a Mantel test
      approach. RESULTS: Genetic differentiation between breeds was high (0.16).
      Overall Fst values among herds were high in each breed (0.17, 0.11 and 0.10). Use
      of the Bayesian approach made it possible to identify genetic groups of herds
      within a breed. Significant correlations between the shortest path lengths and
      the Reynolds' genetic distances were found in each breed (0.87, 0.33 and 0.41),
      which demonstrate the influence of exchanges between herds on the genetic
      diversity. Correlation differences between breeds could be explained by
      differences in the average degree of the animal exchange networks, which is a
      measure of the number of exchanges per herd. The two breeds with the highest
      average degree showed the lowest correlation. Information from the exchange
      networks was used to assign individuals to the genetic groups when molecular
      information was incomplete or missing to identify donors for a cryobank.
      CONCLUSIONS: A fine-scale picture of the population genetic structure at the herd
      level was obtained for the three breeds. Network analysis made it possible to
      highlight the influence of exchanges on genetic structure and to complete or
      replace molecular information in establishing a conservation program.

PMID- 22620857
TI  - The validity of a portable clinical force plate in assessment of static postural
      control: concurrent validity study.
AB  - BACKGROUND: The broad use of force plates in clinical settings for postural
      control assessment suggests the need for instruments that are easy to use,
      affordable and readily available. In addition, these instruments of measurement
      should be reliable and valid as adequate reliability and validity are
      prerequisites to making correct inferences. The aim of this study was to examine
      the concurrent validity of postural control measures obtained with a clinical
      force plate. METHODS: Thirty-one healthy adults were recruited. Participants
      completed 1 set of 5 trials on each force plate. Postural control measures
      (centre of pressure [COP] average velocity and sway area) were collected and
      compared using the Midot Posture Scale Analyzer (clinical force plate) and the
      Accugait force plate (criterion measure). Intra class correlation coefficient
      (ICC), standard error of measurement , and paired t-tests were calculated and
      Bland-Altman plots were constructed to compare the force plates and assess
      consistency of measurement and agreement between them. RESULTS: The ICC values
      (ICC = 0.14-0.60) between the two force plates were lower than the acceptable
      value for both COP average velocity and sway area. There was significant
      difference (p > 0.05) in COP average velocity and sway area between the force
      plates. Examination of the plots revealed that there is less difference between
      the force plates in lower magnitudes of COP for average velocity and sway area
      however, the greater the average velocity and sway area, the greater the
      difference between the measures obtained from the two force plates. CONCLUSION:
      Findings of this study showed poor concurrent validity of the clinical force
      plate. This clinical force plate cannot be a replacement for known reliable and
      valid force plates and consequently measures obtained from this force plate
      should be treated with caution especially in a clinical population.

PMID- 22620858
TI  - Heterogeneity of Aeromonas populations in wild and farmed perch, Perca
      fluviatilis L.

PMID- 22620859
TI  - Toll-like receptor 9 in systemic lupus erythematosus, impact on glucocorticoid
      treatment.
AB  - AIM: To assess TLR9 expression in systemic lupus erythematosus (SLE) patients,
      its correlation with disease activity, and impact of TLR9 expression on the
      response to oral glucocorticoids. METHODS: Twenty-five active SLE, 15 inactive,
      and 15 control subjects were included. Anti-DNA, ANA, C3, C4, and TLR9 mRNA
      expressions were assessed. Active SLE patients only received oral steroid for 6
      weeks. Post therapy, they were classified into steroid sensitive and steroid
      resistant. Data were reassessed after treatment. RESULTS: SLEDAI, anti-DNA, ANA,
      and TLR9 expressions were significantly higher in active SLE patients. Based on
      retrograde analysis, TLR9 expression was significantly higher in steroid
      resistant versus steroid-sensitive group before treatment, with no significant
      difference between them after treatment. There was a significant positive
      correlation between TLR9 expression and SLEDAI score and anti-DNA and negative
      correlation with C3 and C4 in all patients. CONCLUSION: TLR9 may play a role in
      the pathogenesis of SLE and correlates with the disease activity. Corticosteroids
      have no effect on TLR9 expression, explaining lack of corticosteroid response in
      some SLE patients. TLR 9 expression can be used in predicting glucocorticoid
      response in active SLE patients. New treatment modalities targeting TLR9
      expression may be of value in steroid-resistant patients.

PMID- 22620860
TI  - Interactional effects of beta-glucan, starch, and protein in heated oat slurries
      on viscosity and in vitro bile acid binding.
AB  - Three major oat components, beta-glucan, starch, and protein, and their
      interactions were evaluated for the impact on viscosity of heated oat slurries
      and in vitro bile acid binding. Oat flour from the experimental oat line "N979"
      (7.45% beta-glucan) was mixed with water and heated to make oat slurry. Heated
      oat slurries were treated with alpha-amylase, lichenase, and/or proteinase to
      remove starch, beta-glucan, and/or protein. Oat slurries treated with lichenase
      or lichenase combined with alpha-amylase and/or proteinase reduced the molecular
      weight of beta-glucan. Heat and enzymatic treatment of oat slurries reduced the
      peak and final viscosities compared with the control. The control bound the least
      amount of bile acids (p < 0.05); heating of oat flour improved the binding.
      Heated oat slurries treated with lichenase or lichenase combined with alpha
      amylase and/or proteinase bound the least amount of bile acid, indicating the
      contribution of beta-glucan to binding. Oat slurries treated with proteinase or
      proteinase and alpha-amylase together improved the bile acid binding, indicating
      the possible contribution of protein to binding. These results illustrate that
      beta-glucan was the major contributor to viscosity and in vitro bile acid binding
      in heated oat slurries; however, interactions with other components, such as
      protein and starch, indicate the importance of evaluating oat components as whole
      system.

PMID- 22620861
TI  - Quantitative analysis of sildenafil and tadalafil in various fake drugs recently
      distributed in Korea.
AB  - Illicit distribution of various illicit or counterfeit drugs containing
      sildenafil and tadalafil has increased and caused noticeable problems in Korea.
      This study has been performed to determine the content range of sildenafil and
      tadalafil in various fake drugs. Among the illicit or counterfeit drugs seized by
      Korean authorities, 105 exhibits were used for the quantification. HPLC-UV
      analysis of methanol extractions was used for separation and quantitation of the
      two target compounds. The most abundant type of fake drug was counterfeit
      Viagra((r)) tablets. Sildenafil was found in 73 exhibits, and tadalafil was found
      in seven exhibits. Twenty-five exhibits out of the 105 contained both sildenafil
      and tadalafil. The contents of sildenafil ranged from 4.3 to 453.2 mg; for
      tadalafil, the range was 2.2-40.4 mg. The proportion of cases of having more than
      100 mg of sildenafil was 50% and 78% had more than 20 mg of tadalafil.

PMID- 22620862
TI  - Tuberculosis associated immune reconstitution inflammatory syndrome in patients
      infected with HIV: meningitis a potentially life threatening manifestation.
AB  - BACKGROUND: Tuberculosis (TB) is the most common co infection in HIV-infected
      persons in India, requiring concomitant administration of anti TB and
      antiretroviral therapies. Paradoxical worsening of tuberculosis after anti
      retroviral therapy (ART) initiation is frequently seen. OBJECTIVE: To study the
      frequency, clinical presentation and outcome of paradoxical tuberculosis
      associated immune reconstitution inflammatory syndrome (TB-IRIS) in HIV infected
      patients in a TB hospital in North India. DESIGN: A retrospective chart review of
      HIV-infected TB patients on anti-tubercular treatment (ATT) at time of ART
      initiation over a 3 year period. Medical records were reviewed for clinical
      manifestations and outcome in patients who developed TB-IRIS. RESULTS: 514 HIV
      infected patients were enrolled between January 2006 and December 2008. Thirteen
      (12.6%) of 103 patients who had received ART and ATT simultaneously developed
      paradoxical TB-IRIS. Clinical presentations of paradoxical TB-IRIS included new
      lymphadenopathy (n = 3), increase in size of existing lymphadenopathy (n = 3),
      worsening of existing pulmonary lesions (n = 2), appearance of new pleural
      effusion (n = 1) and prolonged high grade fever (n = 2). Four patients developed
      new tubercular meningitis as manifestation of TB-IRIS. Our cases developed TB
      IRIS a median of 15 days after starting ART (IQR 15-36). TB-IRIS patients were
      older (> 35 years) than those with no IRIS (P = 0.03), but were not
      distinguishable by CD4 T-cell count, duration of ATT before ART or the outcome of
      TB treatment. Eight (62%) patients had a complete recovery while 5 (38%) patients
      with TB-IRIS died, of which majority (n = 3) had meningitis. CONCLUSIONS:
      Paradoxical TB-IRIS is a frequent problem during concomitant ATT and ART in HIV
      TB co infected patients in north India. Meningitis is a potentially life
      threatening manifestation of TB-IRIS.

PMID- 22620863
TI  - Low-risk identification in multiple myeloma using a new 14-gene model.
AB  - Identifying the best gene expression pattern associated with low-risk disease in
      patients with newly diagnosed multiple myeloma (MM) is important to direct
      clinical treatments. The MM Survival Index14 (MMSI14) was developed from GEP data
      sets of 22 normal plasma cells (NPC), 5 MM cell lines (MMCL), 44 monoclonal
      gammopathy of undetermined significance (MGUS), and 351 newly diagnosed MM
      patients. R/bioconductor and siggenes package were used to obtain heatmap,
      boxplot and histogram whose results were then analyzed by Kaplan-Meier analysis.
      Fourteen genes associated with low-risk disease in MM were identified. We
      validated the disease prognostic power of MMSI14 with an independent data set of
      other 214 newly diagnosed MM patients and also compared our model with the 70
      gene, the 8-subgroup, IFM15, and HMCLs7 models. Survival analysis showed that a
      low MMSI14 signature was associated with longer survival. Applying MMSI14 to
      independent data sets, we were able to classify 39% of patients as low-risk, with
      a survival probability of more than 90% at 60 months. Multiple clinical
      parameters confirmed significant correlation between low- and high-risk subgroups
      defined by MMSI14. Comparing previously published models to the same data sets
      the MMSI14 model retained the best prognostic value. We have developed a new gene
      model (MMSI14) for defining low-risk, newly diagnosed MM. The multivariate
      comparative analysis confirmed that MMSI14 is the best available model to predict
      clinical outcome in MM patients.

PMID- 22620864
TI  - X-ray spectroscopy of heterocyclic biochemicals: xanthine, hypoxanthine, and
      caffeine.
AB  - The electronic structures of the purine derivatives xanthine, hypoxanthine and
      caffeine have been investigated in the gas phase using C, N, and O 1s X-ray
      photoemission (XPS) and near edge X-ray absorption fine structure (NEXAFS)
      spectroscopy. The results have been interpreted by means of ab initio
      calculations using the third-order algebraic-diagrammatic construction (ADC(3))
      method for the one-particle Green's function and the second-order ADC method
      (ADC(2)) for the polarization propagator. The carbon, nitrogen and oxygen K-edge
      NEXAFS spectra of xanthine and caffeine are very similar, since the molecules
      differ only by substitution of three hydrogen atoms by methyl groups. For
      hypoxanthine, the electronic structure and spectra differ considerably from
      xanthine as the purine ring is more highly conjugated, and there is one less oxo
      group. Effects due to oxo-hydroxy tautomerism were not observed. However, the two
      oxo tautomeric forms of hypoxanthine oxo-N(9)-H and oxo-N(7)-H are populated in
      the gas phase, and the C 1s spectra can be simulated only by taking account of
      these two tautomers, with appropriate Boltzmann population ratios which we have
      also calculated. For xanthine and caffeine, single tautomeric forms were
      observed.

PMID- 22620961
TI  - A report on VIIIth international symposium on familial amyloidotic polyneuropathy
      and VIIth international symposium on liver transplantation in familial
      amyloidotic polyneuropathy.

PMID- 22620865
TI  - Determination of 15N chemical shift anisotropy from a membrane-bound protein by
      NMR spectroscopy.
AB  - Chemical shift anisotropy (CSA) tensors are essential in the structural and
      dynamic studies of proteins using NMR spectroscopy. Results from relaxation
      studies in biomolecular solution and solid-state NMR experiments on aligned
      samples are routinely interpreted using well-characterized CSA tensors determined
      from model compounds. Since CSA tensors, particularly the (15)N CSA, highly
      depend on a number of parameters including secondary structure, electrostatic
      interaction, and the amino acid sequence, there is a need for accurately
      determined CSA tensors from proteins. In this study, we report the backbone amide
      (15)N CSA tensors for a 16.7-kDa membrane-bound and paramagnetic-heme containing
      protein, rabbit Cytochrome b(5) (cytb(5)), determined using the (15)N CSA/(15)N
      (1)H dipolar transverse cross-correlation rates. The mean values of (15)N CSA
      determined for residues in helical, sheet, and turn regions are -187.9, -166.0,
      and -161.1 ppm, respectively, with an overall average value of -171.7 ppm. While
      the average CSA value determined from this study is in good agreement with
      previous solution NMR experiments on small globular proteins, the CSA value
      determined for residues in helical conformation is slightly larger, which may be
      attributed to the paramagnetic effect from Fe(III) of the heme unit in cytb(5).
      However, like in previous solution NMR studies, the CSA values reported in this
      study are larger than the values measured from solid-state NMR experiments. We
      believe that the CSA parameters reported in this study will be useful in
      determining the structure, dynamics, and orientation of proteins, including
      membrane proteins, using NMR spectroscopy.

PMID- 22620962
TI  - Genotype--phenotype correlation in FAP.
AB  - Familial Amyloidotic Polyneuropathy (FAP) was initially classified into different
      types based on the clinical presentation. FAP Type I included patients with
      predominant upper limb neuropathy, while Type II patients had initial lower limb
      involvement. Further confusing the issue was the description of FAP Types III and
      IV, which proved to result from proteins other than Transthyretin (TTR). More
      recently, molecular classification has superseded clinical classification. It is
      increasingly clear that the clinical picture of patients with FAP is widely
      variable. Significant variation in the clinical presentation occurs between
      individual kindreds with the same mutation and even among family members. The
      factors that govern this variation are unknown at present. Some general
      principles have emerged from studying patients with different mutations.
      Leptomeningeal involvement is rare and occurs predominantly in only a few
      mutations. Isolated cardiac involvement in African-Americans is invariably
      associated with the V122I mutation. Given the variability in presentation, it is
      not possible to accurately classify patients on the basis of neuropathy, either
      sensorimotor or autonomic. Further, cardiac involvement, which occurs with
      increased frequency in non-V30M patients, is not a reliable phenotype to
      distinguish specific mutations. Molecular classification has become the gold
      standard for classification of the different forms of FAP. While some rare
      mutations confer a more predictable phenotype, the majority of the known
      mutations are associated with a wide variation in phenotype.

PMID- 22620963
TI  - TTR-familial amyloid polyneuropathy--neurological aspects.
AB  - Transthyretin familial amyloid polyneuropathy is characterized by a devastating
      sensory-motor polyneuropathy associated with life-threatening autonomic
      disturbance. An early diagnosis is mandatory to increase the chance to modify the
      course of the disease. This paper underlines the diagnostic problems encountered
      in this condition.

PMID- 22620964
TI  - Focus on autonomic dysfunction in familial amyloidotic polyneuropathy (FAP).
AB  - It is well known that autonomic dysfunction in familial amyloidotic
      polyneuropathy (FAP) is the most serious problem, because it restricts the daily
      life of these patients. The detail mechanisms of the onset are not well
      understood in FAP and domino liver transplantation-induced amyloid neuropathy. As
      autonomic disturbances play an important role in the symptomatology of FAP,
      further studies of autonomic dysfunction in these patients may lead the
      pathogenesis of FAP. Autonomic dysfunction is often observed before sensory and
      motor nerve dysfunction in FAP. This can be attributed to the morphological
      characteristics of the nerves. Unmyelinated, small myelinated, and large
      myelinated fibers tend to become impaired in that order. Although the reasons of
      susceptibility to amyloid infiltration and injury are not known, studies of
      autopsied FAP patients have revealed heavy infiltration of amyloid in autonomic
      ganglions. Moreover, spinal ganglion and posterior loot of the spine had severe
      amyloid deposits than did the anterior root of the spine or the motor nerves. It
      is well known that autonomic dysfunction is the most serious problem, because it
      restricts the daily life of FAP patients. However, we have four major questions
      about autonomic dysfunction in clinical. In this manuscript, we discuss about the
      answers of these questions.

PMID- 22620965
TI  - Natural polyphenols as modulators of TTR amyloidogenesis: in vitro and in vivo
      evidences towards therapy.
AB  - Several natural polyphenols have been reported to act on different amyloidogenic
      proteins inhibiting amyloid formation therefore we decided to test their effect
      on transthyretin (TTR) amyloid formation. We found that epigallocatechin-3
      gallate (EGCG), curcumin and nordihydroguaiaretic acid (NDGA) bind to TTR and
      modulate its amyloidogenicity, in vitro, although through different mechanisms of
      action. Based on these in vitro studies, we decided to test EGCG in vivo using
      mice models for familial amyloidotic polyneuropathy (FAP). Therefore, we
      performed a subchronic administration of EGCG to mice, for 6 weeks. Next, we
      assessed the effects of EGCG treatment by immunohistochemistry (IHC) and western
      blot analysis of mice tissues. The results obtained demonstrate that EGCG
      inhibits TTR aggregates deposition in about 50% along the gastrointestinal (GI)
      tract and peripheral nervous system (PNS) and lowered the levels of several FAP
      associated biomarkers. Furthermore, treatment of old FAP mice with EGCG resulted
      not only in the decrease of nonfibrillar TTR deposition but also in the
      disaggregation of congophilic amyloid deposits. The dual effect as inhibitor of
      aggregation and as disruptor of amyloid together with its low toxicity indicates
      that EGCG presents a therapeutic application in FAP.

PMID- 22620966
TI  - Potential use of glucuronylglucosyl-beta-cyclodextrin as a novel therapeutic tool
      for familial amyloidotic polyneuropathy.
AB  - Transthyretin (TTR)-related familial amyloidotic polyneuropathy, which is induced
      by amyloidogenic transthyretin (ATTR), is characterized by systemic accumulation
      of amyloid fibrils. Although it is believed that protein misfolding of monomeric
      form of TTR is a rate-limiting step for TTR amyloid formation, no effective
      therapy targeting this misfolding step is available. Our recent studies revealed
      that cyclodextrins (CyDs), cyclic oligosaccharides composed of glucose units,
      might interact with TTR and prevent the protein misfolding. In this study, we
      focused on and elucidated the inhibitory effect of 6-O-alpha-(4-O-alpha-D
      Glucuronyl)-D-glucosyl-beta-CyD (GUG-beta-CyD) on TTR amyloid formation.
      Tryptophan (Trp) fluorescence and (1)H-NMR spectroscopy analyses indicated that
      GUG-beta-CyD stabilized TTR conformation via interaction with the hydrophobic
      amino acids of TTR. Moreover, GUG-beta-CyD suppressed TTR deposition in
      transgenic rats possessing a human ATTR V30M gene in vivo. Collectively, these
      data indicate that GUG-beta-CyD may inhibit TTR misfolding by stabilizing its
      conformation, which, in turn, suppresses TTR amyloid formation.

PMID- 22620967
TI  - Genotypic and phenotypic correlation in an Italian population of hereditary
      amyloidosis TTR-related (HA-TTR): clinical and neurophysiological aids to
      diagnosis and some reflections on misdiagnosis.
AB  - 131 HA-TTR patients from a single referral centre presented at onset five major
      clinical syndromes: (1) the typical "Portuguese variant" axonal polyneuropathy
      with dissociated (syringomyelic like) sensory loss and autonomic dysfunction; (2)
      bilateral carpal tunnel syndrome; (3) restless leg syndrome with impotence and
      unexplained loss of weight; (4) pure motor neuropathy without autonomic
      abnormalities; (5) recurrent small brain or spinal cord ischemia or haemorrhages
      with leptomeningeal amyloid deposition (and late superficial siderosis of the
      central nervous system) and vitreous deposits. Some patients in our population
      presented a "pseudodemyelinating" onset of the somatic neuropathy, as well as
      atypical motor neuropathy simulating lower motor neuron disease. The five
      syndromes can overlap in advanced stages of the disease. Genetic screening of HA
      TTR could be worthwhile in any idiopathic progressive axonal peripheral
      neuropathy, as well as in drug resistant demyelinating sensory-motor neuropathy
      or in pure motor neuropathy, when multi-organ involvement is present.

PMID- 22620968
TI  - Regional difference and similarity of familial amyloidosis with polyneuropathy in
      France.
AB  - Familial amyloidosis with polyneuropathy (FAP) in France have a large genetic
      heterogeneity with 29 transthyretin (TTR) gene mutations; Met30-TTR is the most
      frequent one (62%); followed by Tyr77-TTR (11.8%) and Phe77-TTR (6.2%). Analysis
      of 60 FAP patients diagnosed during the period 2008-2010 showed amyloid
      polyneuropathy was initially suspected in only 38% patients. TTR Met30 of
      Portuguese ancestry is different from TTR Met30 of non Portuguese ancestry and
      other non Met30 variants in geographical distribution and clinical presentation.
      There are three additional phenotypes of the neuropathy including multifocal
      upper limbs neuropathy, ataxic polyneuropathy and motor neuropathy. Patients with
      Tyr77-TTR are characterized by a late onset (>50 years), frequent ataxic
      phenotype; they are localized mainly in north of France. The more frequent use of
      the TTR genetic tests and the French network for FAP will help in the future to
      improve diagnosis and care.

PMID- 22620969
TI  - Senile systemic amyloidosis: are regional differences real or do they reflect
      different diagnostic suspicion and use of techniques?
AB  - Amyloid deposits in the heart derived from transthyretin are commonly seen at
      autopsy in elderly patients. Massive deposition, causing senile systemic
      amyloidosis (SSA), is considered to be relatively uncommon and reported series
      suggest that SSA is considerably less common than amyloid light-chain (AL)
      amyloidosis. This article reviews the autopsy prevalence of transthyretin-derived
      cardiac amyloid, addresses whether there is definitive evidence for regional or
      ethnic differences and argues that the reported prevalence of SSA significantly
      underrepresents the true prevalence of the disease which may be as common, or
      commoner, than AL amyloidosis.

PMID- 22620970
TI  - Operative risks of domino liver transplantation for the FAP liver donor and the
      FAP liver recipient.
AB  - This study aimed at evaluating the operative risks of domino liver
      transplantation (LT). Two retrospective analyses were conducted (comparison of
      familial amyloid polyneuropathy (FAP) liver donors [61 patients] versus FAP
      nondonors [39 patients] and FAP liver recipients [61 patients] versus cadaveric
      liver recipients [61 patients]). First analysis showed a 60-day mortality of 6.6%
      for FAP donors and 7.7% for FAP nondonors (p = 1.0). Both groups had similar
      vascular and biliary complication rates. Both groups had similar 1- and 5-year
      patient and graft survival rates (83.4 % versus 87.2%, and 79.8 % versus 71.8%, p
      = 0.7) and (83.3% versus 87.2%, and 79.1% versus 71.8%, p = 0.7). The second
      analysis showed a 1.6% mortality for FAP liver recipients versus 3.2% of the
      control group (p = 1). Both groups had similar morbidity and technical
      complication rates (18.0% versus 13.1%, p = 0.45) and (0.18 versus 0.15, p =
      0.65). Domino procedure doesn't add any risk to FAP donor or recipient. It
      increases the organ pool allowing transplantation of marginal recipients who
      otherwise are denied cadaveric LT.

PMID- 22620971
TI  - Current state of domino transplantation in Japan in terms of surgical procedures
      and de novo amyloid neuropathy.
AB  - The status of domino liver transplantation (DLT) in Japan was evaluated. DLT and
      familial amyloidotic polyneuropathy (FAP) recipients who underwent living donor
      liver transplantation (LDLT) at Kumamoto University were reviewed with attention
      to surgical procedures. Thirty-nine DLTs were performed in Japan until 2010, and
      survival rates at 1 and 3 years were 82% and 63.6%, respectively. Six of 21 DLT
      recipients who survived for more than 3 years developed amyloid depositions
      within organs, and de novo amyloid neuropathy was reported in three patients. DLT
      from FAP recipients in Kumamoto was safely performed with preservation of the
      retrohepatic inferior vena cava in FAP recipients. All 20 FAP recipients who were
      DLT donors are alive with the exception of one who died of the original FAP 9
      years after LDLT. The outcomes of DLT and FAP recipients in Kumamoto were
      satisfactory.

PMID- 22620973
TI  - Interface-directed self-assembly of gold nanoparticles and fabrication of hybrid
      hollow capsules by interfacial cross-linking polymerization.
AB  - Amphiphilic gold nanoparticles (AuNPs) were produced at liquid-liquid interface
      via ligand exchange between hydrophilic AuNPs and disulfide-containing polymer
      chains. By using oil droplets as templates, hybrid hollow capsules with AuNPs on
      the surfaces were obtained after interfacial cross-linking polymerization. The
      volume ratio of toluene to water exerts an important effect on the size of
      capsules. The average size of the capsules increases with the volume ratio.
      Transmission electron microscopy (TEM), scanning electron microscopy (SEM), and
      atomic force microscopy (AFM) were used to characterize the hollow structures. In
      this research, not only one-component but also multicomponent hollow capsules
      were prepared by copolymerization of acrylamide and hybrid AuNPs at liquid-liquid
      interface. Because of the improvement in hydrophilicity of the hollow capsules,
      the average size of multicomponent capsules is bigger than one-component ones in
      aqueous solution.

PMID- 22620974
TI  - Phosphorylation of the synthetic hexasaccharide repeating unit is essential for
      the induction of antibodies to Clostridium difficile PSII cell wall
      polysaccharide.
AB  - Clostridium difficile is emerging worldwide as a major cause of nosocomial
      infections. The negatively charged PSII polysaccharide has been found in
      different strains of C. difficile and, thereby, represents an important target
      molecule for a possible carbohydrate-based vaccine. In order to identify a
      synthetic fragment that after conjugation to a protein carrier could be able to
      induce anti-PSII antibodies, we exploited a combination of chemical synthesis
      with immunochemistry, confocal immunofluorescence microscopy, and solid state
      NMR. We demonstrate that the phosphate group is crucial in synthetic glycans to
      mimic the native PSII polysaccharide; both native PSII and a phosphorylated
      synthetic hexasaccharide repeating unit conjugated to CRM(197) elicit comparable
      immunogenic responses in mice. This finding can aid design and selection of
      carbohydrate antigens to be explored as vaccine candidates.

PMID- 22620975
TI  - Ego identity development in physicians: a cross-cultural comparison using a mixed
      method approach.
AB  - BACKGROUND: The purpose of this study was to examine the career decision-making
      process of International Medical Graduates (IMGs). There are two main types of
      IMGs who apply for licensure in Canada. Canadian International Medical Graduates
      (CIMGs) were Canadian citizens before leaving to study medicine in a foreign
      country, in comparison to those non-CIMGs who had studied medicine in a foreign
      country before immigrating to Canada. Given that their motivations for becoming a
      doctor in Canada may differ, it is important to examine how they decided to
      become a doctor for each group separately. METHODS: A total of 46 IMGs
      participated in a semi-structured interview - 20 were CIMGs and 26 were non
      CIMGs. RESULTS: An iterative process of content analysis was conducted to
      categorize responses from five open-ended questions according to the Ego Identity
      Statuses theory of career decision-making. Event contingency analysis identified
      a significant difference between CIMGs and non-CIMGs, Fisher's exact test (1) =
      18.79, p < .0001. A total of 55% of CIMGs were categorized as identity achieved
      and 45% as foreclosed; 100% of non-CIMGs were classified as identity foreclosed.
      CONCLUSION: About half of the Canadian citizens who had studied medicine in a
      foreign country had explored different careers before making a commitment to
      medicine, and half had not. No IMGs, however, who studied medicine in another
      country before immigrating to Canada, had explored various career opportunities
      before selecting medicine.

PMID- 22620976
TI  - Substances released from probiotic Lactobacillus rhamnosus GR-1 potentiate NF
      kappaB activity in Escherichia coli-stimulated urinary bladder cells.
AB  - Lactobacillus rhamnosus GR-1 is a probiotic bacterium used to maintain urogenital
      health. The putative mechanism for its probiotic effect is by modulating the host
      immunity. Urinary tract infections (UTI) are often caused by uropathogenic
      Escherichia coli that frequently evade or suppress immune responses in the
      bladder and can target pathways, including nuclear factor-kappaB (NF-kappaB). We
      evaluated the role of L. rhamnosus GR-1 on NF-kappaB activation in E. coli
      stimulated bladder cells. Viable L. rhamnosus GR-1 was found to potentiate NF
      kappaB activity in E. coli-stimulated T24 bladder cells, whereas heat-killed
      lactobacilli demonstrated a marginal increase in NF-kappaB activity. Surface
      components released by trypsin- or LiCl treatment, or the resultant heat-killed
      shaved lactobacilli, had no effect on NF-kappaB activity. Isolation of released
      products from L. rhamnosus GR-1 demonstrated that the induction of NF-kappaB
      activity was owing to released product(s) with a relatively large native size.
      Several putative immunomodulatory proteins were identified, namely GroEL,
      elongation factor Tu and NLP/P60. GroEL and elongation factor Tu have previously
      been shown to elicit immune responses from human cells. Isolating and using
      immune-augmenting substances produced by lactobacilli is a novel strategy for the
      prevention or treatment of UTI caused by immune-evading E. coli.

PMID- 22620977
TI  - Prevention of death and disability from injuries to children and adolescents.
AB  - One million children and adolescents die each year from injuries and many-fold
      more suffer long-term disability. While there have been substantial reductions in
      injury mortality over the last 50 years, further decreases in morbidity and
      mortality will require consideration of additional factors. This article
      discusses five different components to further reduce the injury burden:
      consideration of the epidemiologic transition occurring in both high-income as
      well as low- and middle-income countries; expanding the concept of injury
      prevention to that of injury control, with substantial emphasis on acute care and
      rehabilitation of the injured child; inclusion of adolescents in paediatric
      injury control; improving the quality of research conducted; and changing the way
      priorities are determined in the injury field.

PMID- 22620978
TI  - Using the G' Raman cross-section to understand the phonon dynamics in bilayer
      graphene systems.
AB  - The G' (or 2D) Raman band of AB stacked bilayer graphene comes from a double
      resonance Raman (DRR) process and is composed of four peaks (P(11), P(12), P(21),
      and P(22)). In this work, the integrated areas (IA) of these four peaks are
      analyzed as a function of the laser power for different laser lines. We show that
      the dependence of the IA of each peak on temperature is different for each
      distinct laser excitation energy. This special dependence is explained in terms
      of the electron-phonon coupling and the relaxation of the photon-excited
      electron. In this DRR process, the electron is scattered by an iTO phonon from a
      K to an inequivalent K' point of the Brillouin zone. Here, we show that this
      electron relaxes while in the conduction band before being scattered by an iTO
      phonon due to the short relaxation time of the excited electron, and the carrier
      relaxation occurs predominantly by emitting a low-energy acoustic phonon. The
      different combinations of relaxation processes determine the relative intensities
      of the four peaks that give rise to the G' band. Some peaks show an increase of
      their IA at the expense of others, thereby making the IA of the peaks both
      different from each other and dependent on laser excitation energy and on power
      level. Also, we report that the IA of the G' mode excited at 532 nm, shows a
      resonance regime involving ZO' phonons (related to the interlayer breathing mode
      in bilayer graphene systems) in which a saturation of what we call the P(12)
      process occurs. This effect gives important information about the electron and
      phonon dynamics and needs to be taken into account for certain applications of
      bilayer graphene in the field of nanotechnology.

PMID- 22620979
TI  - Lonafarnib for cancer and progeria.
AB  - INTRODUCTION: Lonafarnib is a non-peptidomimetic inhibitor of farnesyl
      transferase, an enzyme responsible for the post-translational lipid modification
      of a wide variety of cellular proteins that are involved in the pathogenic
      pathways of various diseases including cancer and progeria. Although extensive
      clinical research indicates limited activity of lonafarnib in solid tumors, there
      is recent interest in combinations of farnesyl transferase inhibitors with
      imatinib or bortezomib in hematological malignancies and to investigate the role
      of lonafarnib in progeria. AREAS COVERED: This review examines the in vitro and
      in vivo pharmacology of lonafarnib and the available clinical data for lonafarnib
      monotherapy and combination therapy in the treatment of solid and hematological
      malignancies as well as progeria, using studies identified from the PubMed
      database supplemented by computerized search of relevant abstracts from major
      cancer and hematology conferences. EXPERT OPINION: There is no evidence to
      support the use of lonafarnib in solid tumors. There is ongoing interest to
      explore lonafarnib for progeria and to investigate other farnesyl transferase
      inhibitors for chronic and acute leukemias.

PMID- 22620980
TI  - Q-switched laser therapy for recalcitrant and recurrent pigmentation after
      chemical depigmentation for extensive vitiligo.

PMID- 22620982
TI  - Molecular mechanisms of seed dormancy.
AB  - Seed dormancy is an important component of plant fitness that causes a delay of
      germination until the arrival of a favourable growth season. Dormancy is a
      complex trait that is determined by genetic factors with a substantial
      environmental influence. Several of the tissues comprising a seed contribute to
      its final dormancy level. The roles of the plant hormones abscisic acid and
      gibberellin in the regulation of dormancy and germination have long been
      recognized. The last decade saw the identification of several additional factors
      that influence dormancy including dormancy-specific genes, chromatin factors and
      non-enzymatic processes. This review gives an overview of our present
      understanding of the mechanisms that control seed dormancy at the molecular
      level, with an emphasis on new insights. The various regulators that are involved
      in the induction and release of dormancy, the influence of environmental factors
      and the conservation of seed dormancy mechanisms between plant species are
      discussed. Finally, expected future directions in seed dormancy research are
      considered.

PMID- 22620981
TI  - Targeting NADPH oxidase decreases oxidative stress in the transgenic sickle cell
      mouse penis.
AB  - INTRODUCTION: Sickle cell disease (SCD) is a state of chronic vasculopathy
      characterized by endothelial dysfunction and increased oxidative stress, but the
      sources and mechanisms responsible for reactive oxygen species (ROS) production
      in the penis are unknown. AIMS: We evaluated whether SCD activates NADPH oxidase,
      induces endothelial nitric oxide synthase (eNOS) uncoupling, and decreases
      antioxidants in the SCD mouse penis. We further tested the hypothesis that
      targeting NADPH oxidase decreases oxidative stress in the SCD mouse penis.
      METHODS: SCD transgenic (sickle) mice were used as an animal model of SCD.
      Hemizygous (hemi) mice served as controls. Mice received an NADPH oxidase
      inhibitor apocynin (10 mM in drinking water) or vehicle. Penes were excised at
      baseline for molecular studies. Markers of oxidative stress (4-hydroxy-2-nonenal
      [HNE]), sources of ROS (eNOS uncoupling and NADPH oxidase subunits p67(phox) ,
      p47(phox) , and gp91(phox) ), and enzymatic antioxidants (superoxide dismutase
      [SOD]1, SOD2, catalase, and glutathione peroxidase-1 [GPx1]) were measured by
      Western blot in penes. MAIN OUTCOME MEASURES: Sources of ROS, oxidative stress,
      and enzymatic antioxidants in the SCD penis. RESULTS: Relative to hemi mice, SCD
      increased (P<0.05) protein expression of NADPH oxidase subunits p67(phox) ,
      p47(phox) , and gp91(phox) , 4-HNE-modified proteins, induced eNOS uncoupling,
      and reduced Gpx1 expression in the penis. Apocynin treatment of sickle mice
      reversed (P<0.05) the abnormalities in protein expressions of p47(phox) ,
      gp91(phox) (but not p67(phox) ) and 4-HNE, but only slightly (P>0.05) prevented
      eNOS uncoupling in the penis. Apocynin treatment of hemi mice did not affect any
      of these parameters. CONCLUSION: NADPH oxidase and eNOS uncoupling are sources of
      oxidative stress in the SCD penis; decreased GPx1 further contributes to
      oxidative stress. Inhibition of NADPH oxidase upregulation decreases oxidative
      stress, implying a major role for NADPH oxidase as a ROS source and a potential
      target for improving vascular function in the SCD mouse penis.

PMID- 22620983
TI  - Processes of enhanced self-understanding during a counselling programme for
      parents of children with disabilities.
AB  - BACKGROUND: The stress and burden on parents of children with disabilities are
      well documented, and the parents' way of handling the situation is crucial to the
      health and well-being of all family members, including the child with special
      needs. We conducted a group-based counselling programme for parents, based mainly
      on Gestalt education and personal construct theories, aiming at increasing the
      parents' ability to handle the situation. AIMS: To explore the parents'
      experiences from processes of change after the counselling programme. METHOD
      DESIGN: This qualitative study is based on modified grounded theory. METHOD: The
      study conducted in Norway examines the experiences of 67 parents (of whom 29
      fathers) of children with disabilities. Information was collected through focus
      group discussions after finishing their sessions of the counselling programme.
      FINDINGS: From the parents' experiences, the following categories were developed:
      feeling motivated to communicate, describing oneself in new words, being inspired
      to experience one's own emotions, being more present and in charge and making a
      difference by taking new steps. The core category in our analysis turned out to
      be Improved handling of the situation by enhanced self-understanding. The parents
      seemed to redevelop their self-understanding through new experiences of
      themselves. They emphasized the importance of a secure setting of peers with
      similar experiences and skilled counsellors to feel free to explore one's own
      emotions with connecting thoughts and bodily reactions. Discussion of existential
      issues as one's own values also contributed to enhanced self-understanding, which
      strengthened the parents to find new possibilities and priorities in handling the
      situation. CONCLUSIONS: The parents described subjective processes of awareness
      and self-reflection as important for being able to start a process towards
      enhanced self-understanding, which helped to detect one's own values and new ways
      of acting. These experiences may be relevant for the parents and for the
      conduction of future counselling.

PMID- 22620984
TI  - Larvicidal activity of ajowan ( Trachyspermum ammi ) and Peru balsam ( Myroxylon
      pereira ) oils and blends of their constituents against mosquito, Aedes aegypti ,
      acute toxicity on water flea, Daphnia magna , and aqueous residue.
AB  - This study evaluated the larvicidal activity of 20 plant essential oils and
      components from ajowan ( Trachyspermum ammi ) and Peru balsam ( Myroxylon pereira
      ) oils against the mosquito, Aedes aegypti . Of the 20 plant essential oils,
      ajowan and Peru balsam oils at 0.1 mg/mL exhibited 100 and 97.5% larval
      mortality, respectively. At this same concentration, the individual constituents,
      (+)-camphene, benzoic acid, thymol, carvacrol, benzyl benzonate, and benzyl trans
      cinnamate, caused 100% mortality. The toxicity of blends of constituents
      identified in two active oils indicated that thymol and benzyl benzoate were
      major contributors to the larvicidal activity of the artificial blend. This study
      also tested the acute toxicity of these two active oils and their major
      constituents against the water flea, Daphnia magna . Peru balsam oil and benzyl
      trans-cinnamate were the most toxic to D. magna. Two days after the treatment,
      residues of ajowan and Peru balsalm oils in water were 36.2 and 85.1%,
      respectively. Less than 50% of benzyl trans-cinnamate and thymol were detected in
      the water at 2 days after treatment. The results show that the essential oils of
      ajowan and Peru balsam and some of their constituents have potential as botanical
      insecticides against Ae. aegypti mosquito larvae. 

PMID- 22620985
TI  - A dodecanuclear dysprosium wheel assembled by six vertex-sharing Dy3 triangles
      exhibiting slow magnetic relaxation.
AB  - Reactions of lanthanide(III) (Ln(III)) perchlorate (Ln = Dy and Ho) and a
      polydentate Schiff base resulted in the unprecedented assembly of novel Ln(12)
      wheels containing six vertex-sharing Ln(3) triangles. The Dy(12) derivative
      represents the largest lanthanide wheel based on the peculiar Dy(3) triangles
      showing slow magnetic relaxation.

PMID- 22620986
TI  - Dexmedetomidine as adjunct treatment for severe alcohol withdrawal in the ICU.
AB  - BACKGROUND: Patients undergoing alcohol withdrawal in the intensive care unit
      (ICU) often require escalating doses of benzodiazepines and not uncommonly
      require intubation and mechanical ventilation for airway protection. This may
      lead to complications and prolonged ICU stays. Experimental studies and single
      case reports suggest the alpha2-agonist dexmedetomidine is effective in managing
      the autonomic symptoms seen with alcohol withdrawal. We report a retrospective
      analysis of 20 ICU patients treated with dexmedetomidine for benzodiazepine
      refractory alcohol withdrawal. METHODS: Records from a 23-bed mixed medical
      surgical ICU were abstracted from November 2008 to November 2010 for patients who
      received dexmedetomidine for alcohol withdrawal. The main analysis compared
      alcohol withdrawal severity scores and medication doses for 24 h before
      dexmedetomidine therapy with values during the first 24 h of dexmedetomidine
      therapy. RESULTS: There was a 61.5% reduction in benzodiazepine dosing after
      initiation of dexmedetomidine (n = 17; p < 0.001) and a 21.1% reduction in
      alcohol withdrawal severity score (n = 11; p = .015). Patients experienced less
      tachycardia and systolic hypertension following dexmedetomidine initiation. One
      patient out of 20 required intubation. A serious adverse effect occurred in one
      patient, in whom dexmedetomidine was discontinued for two 9-second asystolic
      pauses noted on telemetry. CONCLUSIONS: This observational study suggests that
      dexmedetomidine therapy for severe alcohol withdrawal is associated with
      substantially reduced benzodiazepine dosing, a decrease in alcohol withdrawal
      scoring and blunted hyperadrenergic cardiovascular response to ethanol
      abstinence. In this series, there was a low rate of mechanical ventilation
      associated with the above strategy. One of 20 patients suffered two 9-second
      asystolic pauses, which did not recur after dexmedetomidine discontinuation.
      Prospective trials are warranted to compare adjunct treatment with
      dexmedetomidine versus standard benzodiazepine therapy.

PMID- 22620987
TI  - Synthesis and biological evaluation of purpurealidin E-derived marine sponge
      metabolites: aplysamine-2, aplyzanzine A, and suberedamines A and B.
AB  - Five purpurealidin-derived marine secondary sponge metabolies have been
      synthesized through the carbodiimide coupling of an appropriate bromotyrosine
      unit. The structure elucidations have been confirmed through direct comparison
      with spectroscopic data of isolated natural products. Aplyzanzine A has been
      shown to be the most active product against a broad bacterial and fungal screen,
      demonstrating MIC values 2 to 4 times lower than the other metabolites in this
      study. Compounds 2, 3, 4a, and 5-7 exhibit a modest inhibition against slow
      growing mycobacteria (MIC 25-50 MUg/mL), including Mycobacterium tuberculosis.
      iso-Anomoian A and suberedamine B showed antitumor activity in the NCI-DTP60 cell
      line screen at single-digit micromolar concentrations, with iso-anomoian A
      inhibiting 53 cell lines. These molecules present novel scaffolds for further
      optimization.

PMID- 22620988
TI  - A study of the atmospherically important reactions between dimethyl selenide
      (DMSe) and molecular halogens (X2 = Cl2, Br2, and I2) with ab initio
      calculations.
AB  - The atmospherically relevant reactions between dimethyl selenide (DMSe) and the
      molecular halogens (X(2) = Cl(2), Br(2), and I(2)) have been studied with ab
      initio calculations at the MP2/aug-cc-pVDZ level of theory. Geometry optimization
      calculations showed that the reactions proceed from the reagents to the products
      (CH(3)SeCH(2)X + HX) via three minima, a van der Waals adduct (DMSe:X(2)), a
      covalently bound intermediate (DMSeX(2)), and a product-like complex
      (CH(3)SeCH(2)X:HX). The computed potential energy surfaces are used to predict
      what molecular species are likely to be observed in spectroscopic experiments
      such as gas-phase photoelectron spectroscopy and infrared matrix isolation
      spectroscopy. It is concluded that, for the reactions of DMSe with Cl(2) and
      Br(2), the covalent intermediate should be seen in spectroscopic experiments,
      whereas, in the DMSe + I(2) reaction, the van der Waals adduct DMSe:I(2) should
      be observed. Comparison is made with previous related calculations and
      experiments on dimethyl sulfide (DMS) with molecular halogens. The relevance of
      the results to atmospheric chemistry is discussed. The DMSeX(2) and DMSe:X(2)
      intermediates are likely to be reservoirs of molecular halogens in the atmosphere
      which will lead on photolysis to ozone depletion.

PMID- 22620989
TI  - Construction of a Salmonella Gallinarum ghost as a novel inactivated vaccine
      candidate and its protective efficacy against fowl typhoid in chickens.
AB  - In order to develop a novel, safe and immunogenic fowl typhoid (FT) vaccine
      candidate, a Salmonella Gallinarum ghost with controlled expression of the
      bacteriophage PhiX174 lysis gene E was constructed using pMMP99 plasmid in this
      study. The formation of the Salmonella Gallinarum ghost with tunnel formation and
      loss of cytoplasmic contents was observed by scanning electron microscopy and
      transmission electron microscopy. No viable cells were detectable 24 h after the
      induction of gene E expression by an increase in temperature from 37  degrees C
      to 42  degrees C. The safety and protective efficacy of the Salmonella Gallinarum
      ghost vaccine was tested in chickens that were divided into four groups: group A
      (non-immunized control), group B (orally immunized), group C (subcutaneously
      immunized) and group D (intramuscularly immunized). The birds were immunized at
      day 7 of age. None of the immunized animals showed any adverse reactions such as
      abnormal behavior, mortality, or signs of FT such as anorexia, depression, or
      diarrhea. These birds were subsequently challenged with a virulent Salmonella
      Gallinarum strain at 3 weeks post-immunization (wpi). Significant protection
      against the virulent challenge was observed in all immunized groups based on
      mortality and post-mortem lesions compared to the non-immunized control group. In
      addition, immunization with the Salmonella Gallinarum ghosts induced
      significantly high systemic IgG response in all immunized groups. Among the
      groups, orally-vaccinated group B showed significantly higher levels of secreted
      IgA. A potent antigen-specific lymphocyte activation response along with
      significantly increased percentages of CD4+ and CD8+ T lymphocytes found in all
      immunized groups clearly indicate the induction of cellular immune responses.
      Overall, these findings suggest that the newly constructed Salmonella Gallinarum
      ghost appears to be a safe, highly immunogenic, and efficient non-living
      bacterial vaccine candidate that protects against FT.

PMID- 22620991
TI  - Pivotal role of water in terminating enzymatic function: a density functional
      theory study of the mechanism-based inactivation of cytochromes P450.
AB  - The importance of the mechanism-based inactivation (MBI) of enzymes, which has a
      variety of physiological effects and therapeutic implications, has been garnering
      appreciation. Density functional theory calculations were undertaken to gain a
      clear understanding of the MBI of a cytochrome P450 enzyme (CYP2B4) by tert
      butylphenylacetylene (tBPA). The results of calculations suggest that, in
      accordance with previous proposals, the reaction proceeds via a ketene-type
      metabolic intermediate. Once an oxoiron(IV) porphyryn pi-cation radical
      intermediate (compound I) of P450 is generated at the heme reaction site, ketene
      formation is facile, as the terminal acetylene of tBPA can form a C-O bond with
      the oxo unit of compound I with a relatively low reaction barrier (14.1
      kcal/mol). Unexpectedly, it was found that the ketene-type intermediate was not
      very reactive. Its reaction with the hydroxyl group of a threonine (Thr302) to
      form an ester bond required a substantial barrier (38.2 kcal/mol). The high
      barrier disfavored the mechanism by which these species react directly. However,
      the introduction of a water molecule in the reaction center led to its active
      participation in the reaction. The water was capable of donating its proton to
      the tBPA molecule, while accepting the proton of threonine. This water-mediated
      mechanism lowered the reaction barrier for the formation of an ester bond by
      about 20 kcal/mol. Therefore, our study suggests that a water molecule, which can
      easily gain access to the threonine residue through the proton-relay channel,
      plays a critical role in enhancing the covalent modification of threonine by
      terminal acetylene compounds. Another type of MBI by acetylenes, N-alkylation of
      the heme prosthetic group, was less favorable than the threonine modification
      pathway.

PMID- 22620990
TI  - Internet-based treatment of pathological gambling with a three-year follow-up.
AB  - Effective therapies for pathological gambling exist, but their use is limited to
      about 10% of the target population. In an attempt to lower the barriers for help,
      Internet-based cognitive behavioural therapy (ICBT) has been shown to be
      effective when delivered to a non-depressed sample with pathological gambling.
      This study sought to extend this finding to a larger, more representative
      population, and also test a model to predict responder status. Following
      advertisement, a total of 284 participants started an 8-week ICBT programme with
      minimal therapist contact via e-mail and weekly telephone calls of less than 15
      min. The average time spent on each participant, including telephone
      conversations, e-mail, and administration, was 4 h. In addition to a mixed
      effects model to evaluate the effectiveness of the treatment, two logistic
      regression analyses were performed with the following eight pre-defined response
      predictor variables: work-life satisfaction, primary gambling activity, debts due
      to gambling, social support, personal yearly salary, alcohol consumption, stage
      of change, and dissociative gambling. ICBT resulted in statistically significant
      reductions in the scores of pathological gambling, anxiety, and depression as
      well as an increase in quality of life compared to pre-treatment levels. Follow
      ups carried out in the treatment group at 6, 18, and 36 months indicated that
      treatment effects were sustained. Using the eight predictor variable model
      rendered an acceptable predictive ability to identify responders both at post
      test (AUC = .72, p < .01) and at 36-month follow-up (AUC = .70, p < .01). We
      conclude that ICBT for pathological gamblers, even if depressed, can be effective
      and that outcome can partly be predicted by pre-treatment characteristics.

PMID- 22621131
TI  - Promoting youth mental health.

PMID- 22621130
TI  - The new temperature-sensitive mutation PA-F35S for developing recombinant avian
      live attenuated H5N1 influenza vaccine.
AB  - BACKGROUND: H5N1 highly pathogenic avian influenza virus (HPAIV) is continuously
      circulating in many Asian countries and threatening poultry industry and human
      population. Vaccination is the best strategy to control H5N1 HPAIV infection in
      poultry and transmission to human population. The aim of this study is to
      identify new temperature-sensitive (ts) mutations for developing recombinant
      avian live attenuated H5N1 influenza vaccine. FINDINGS: A "6 + 2" recombinant
      virus C4/W1 that contained NA gene and modified HA gene from virus
      A/chicken/Hubei/327/2004 (H5N1) (C4), and six internal genes from virus
      A/duck/Hubei/W1/2004 (H9N2) (W1) was generated using reverse genetics and
      subsequently passaged in chicken eggs at progressively lower temperatures (32
      degrees C, 28 degrees C and 25 degrees C). The resulting virus acquired ts
      phenotype and one of its amino acid mutations, PA (F35S), was identified as ts
      mutation. Furthermore, when used as live attenuated vaccine, the recombinant
      virus with this ts mutation PA (F35S) provided efficient protection for chickens
      against H5N1 HPAIV infection. CONCLUSIONS: These findings highlight the potential
      of the new ts mutation PA (F35S) in developing recombinant avian live attenuated
      H5N1 influenza vaccine.

PMID- 22621132
TI  - Internet pornography and adolescent health.

PMID- 22621133
TI  - Does football cause brain damage?

PMID- 22621134
TI  - Evolving psychiatric diagnosis and the DSM: hasten slowly.

PMID- 22621137
TI  - When less can mean more.

PMID- 22621138
TI  - Is it appropriate to treat people at high-risk of psychosis before first onset -
      yes.

PMID- 22621139
TI  - Is it appropriate to treat people at high-risk of psychosis before first onset? -
      no.

PMID- 22621140
TI  - Holding a stillborn baby: does the existing evidence help us provide guidance?

PMID- 22621141
TI  - The need to tackle concussion in Australian football codes.

PMID- 22621142
TI  - Tertiary education institutions should not offer pseudoscientific medical
      courses.

PMID- 22621143
TI  - Clinical pathways and guidelines: a plea for professional independence.

PMID- 22621144
TI  - A big-picture approach to big people.

PMID- 22621145
TI  - Why exercise is an important component of risk reduction in obesity management.

PMID- 22621146
TI  - Designing payments for GPs to improve the quality of diabetes care.

PMID- 22621147
TI  - Mindfulness training: an adjunctive role in the management of chronic illness?
AB  - Narrowly defined, mindfulness is the tendency to encounter moment-to-moment
      experience without being lost in unhelpful or distressing thoughts triggered by
      the experience. Mindfulness training involves group instruction in and discussion
      of a variety of meditation styles aimed at enhancing this tendency in daily life.
      There is an accumulating evidence base, albeit of variable quality, which
      suggests that mindfulness training, when used as part of an integrated approach
      to chronic disease management, may help alleviate associated psychological
      distress and improve patients' quality of life.

PMID- 22621148
TI  - Sudden limb weakness.
AB  - Stroke is a common neurological emergency and may occur in patients of all ages.
      Rapid assessment is crucial for patients with acute neurological symptoms
      suggestive of stroke because the opportunity for a positive outcome from
      thrombolytic treatment diminishes rapidly within the first few hours. Although
      plain non-contrast computed tomography of the brain is adequate to exclude
      haemorrhage and conditions such as malignancy, advanced multimodal imaging can be
      used to assist with decision making regarding the use of recombinant tissue
      plasminogen activator and mechanical clot-retrieval approaches without adding
      significant delay. Excellent outcomes are possible with the early use of
      reperfusion therapies, even when large areas of brain ischaemia are present,
      provided that there is evidence of potentially salvageable brain and that
      treatment can commence without unnecessary delay and hazard.

PMID- 22621149
TI  - Hormone treatment of gender identity disorder in a cohort of children and
      adolescents.
AB  - OBJECTIVE: To describe the experience of hormone treatment of gender identity
      disorder (GID) in children and adolescents within a specialist clinic. DESIGN,
      PATIENTS AND SETTING: Cohort study by medical record review of children aged 0-17
      years referred during 2003-2011 for management at the GID clinic in a tertiary
      paediatric referral centre - the Royal Children's Hospital, Melbourne, Victoria.
      MAIN OUTCOME MEASURES: Clinical characteristics of the patient population,
      hormone treatment provided, frequency of referrals with time. RESULTS: Thirty
      nine children and adolescents were referred for gender dysphoria. Seventeen
      individuals were pubertal with persistent GID, and were considered eligible for
      hormone treatment. Seven patients, comprising three biological males and four
      biological females, had legally endorsed hormone treatment. In this group, gender
      dysphoria was first noted at 3-6 years of age. Hormone treatment with GnRH
      analogue to suppress pubertal progression (phase 1) was given at 10-16 years of
      age. Treatment with cross-sex hormones (phase 2) was given at 15.6-16 years. One
      patient purchased cross-sex hormone treatment overseas. One patient received
      oestrogen and progesterone for menstrual suppression before phase 1. The annual
      frequency of new referrals increased continuously over the study period.
      CONCLUSIONS: Hormone treatment for pubertal suppression and subsequent gender
      transition needs to be individualised within stringent protocols in
      multidisciplinary specialist units.

PMID- 22621150
TI  - Splenectomy sequelae: an analysis of infectious outcomes among adults in
      Victoria.
AB  - OBJECTIVE: To determine the risk and timing of a broad range of infective
      outcomes and mortality after splenectomy. DESIGN, SETTING AND PARTICIPANTS:
      Analysis of a non-identifiable linked hospital discharge administrative dataset
      for splenectomy cases between July 1998 and December 2006 in Victoria, Australia.
      MAIN OUTCOME MEASURES: Age, sex, indication for splenectomy, infectious events
      and death. Patients splenectomised for trauma were compared with patients
      splenectomised for other indications. Infectious risk was established using Cox
      proportional hazards models. RESULTS: A total of 2574 patients underwent
      splenectomy (with 8648 person-years follow-up). Paediatric cases were excluded,
      leaving 2472 adult cases for analysis. The most common reasons for splenectomy
      were trauma (635 [25.7%]) and therapeutic haematological indications (583
      [23.6%]). After splenectomy, 644 adult patients (26.0%) had a severe infection,
      with a rate of 8.0 per 100 person-years (95% CI, 7.2-8.4). The risk of severe
      infection was highest among patients aged > [corrected] 50 years (10.1
      [corrected] per 100 person-years; 95% CI, 9.3-11.1) [corrected] and those
      splenectomised for malignancy (14.2 per 100 person-years; 95% CI, 11.8-17.1).
      Gram-negative infections represented the most frequent causative organism group
      accounting for 698 (51%) of bacterial pathogens. Staphylococcus aureus was the
      second most common causative organism. CONCLUSION: The incidence of severe
      infection and all-cause mortality differed according to age and underlying reason
      for splenectomy, and was highest among the elderly and those with malignancy, and
      was lowest among trauma patients. This highlights the need for targeted
      prevention programs.

PMID- 22621151
TI  - Splenectomy and sepsis.

PMID- 22621152
TI  - Sporotrichosis (Sporothrix schenckii infection) in the New South Wales mid-north
      coast, 2000-2010.
AB  - OBJECTIVE: To determine the geographical, epidemiological and clinical features
      of sporotrichosis (a cutaneous fungal infection caused by Sporothrix schenckii)
      in the New South Wales mid-north coast. DESIGN AND SETTING: We undertook a
      retrospective case review of S. schenckii infections that occurred during the
      period 2000-2010. Microbiology laboratory staff and medical practitioners in the
      NSW mid-north coast were contacted to identify cases through database searches
      and clinical data collection. RESULTS: Thirty-one cases of S. schenckii infection
      were identified. Twenty-one occurred in males, the mean age of patients was 59
      years, and all cases with data available involved cutaneous disease affecting the
      limbs (multiple lesions in 18 of 20 cases). Despite an impression of temporal
      clustering (eight cases in 1 year), this was not statistically significant (P =
      0.3). Most cases occurred in months with higher rainfall (13 of 14 cases with
      data available). Inoculating events included injuries in gardens, in bushland and
      on farms, and possible bites. Symptom duration before correct diagnosis ranged
      from 4 to 30 weeks (median, 8 weeks; data available for 15 cases), unnecessary
      antibacterial therapy was common (13 of 19 cases with data available), and
      morbidity occurred in the form of recurrence (three cases) and mild itraconazole
      induced hepatotoxicity (two cases). In all cases with recorded treatment details,
      the patients received itraconazole, and the median duration of itraconazole
      treatment was 24 weeks. CONCLUSIONS: These data highlight that health providers
      on the NSW mid-north coast should consider sporotrichosis when patients present
      with characteristic lesions after an inoculating injury sustained from or
      contaminated by decaying vegetation. The risk may be higher in older people and
      in wetter months. Fungal culture to confirm the diagnosis needs to be
      specifically requested. In contrast to outbreaks reported from other states, the
      epidemiological pattern in NSW appears most consistent with sporadic occurrence
      in an endemic setting.

PMID- 22621153
TI  - Out of sight, out of mind: making involuntary community treatment visible in the
      mental health system.
AB  - Most specialised mental health services in Australia are delivered in community
      settings and one in six services comprise involuntary treatment. Despite a
      growing demand for community treatment orders (CTOs) worldwide - and
      comparatively high rates of use in Australia - the clinical, legal and ethical
      aspects of CTOs remain contentious. This article examines federal, state and
      territory mental health policy documents and discovers little reference to CTOs.
      The "invisibility" of CTOs in mental health policy raises questions about the
      transparency and accountability of the mental health system, and about whether
      this policy silence ultimately entrenches the marginalisation of, and
      discrimination against, people living with mental illness.

PMID- 22621154
TI  - Simulation in clinical teaching and learning.
AB  - Simulation-based education (SBE) is a rapidly developing method of supplementing
      and enhancing the clinical education of medical students. Clinical situations are
      simulated for teaching and learning purposes, creating opportunities for
      deliberate practice of new skills without involving real patients. Simulation
      takes many forms, from simple skills training models to computerised full-body
      mannequins, so that the needs of learners at each stage of their education can be
      targeted. Emerging evidence supports the value of simulation as an educational
      technique; to be effective it needs to be integrated into the curriculum in a way
      that promotes transfer of the skills learnt to clinical practice. Currently, SBE
      initiatives in Australia are fragmented and depend on local enthusiasts; Health
      Workforce Australia is driving initiatives to develop a more coordinated national
      approach to optimise the benefits of simulation.

PMID- 22621155
TI  - Does it take too long to become a doctor?

PMID- 22621156
TI  - Healed, or hungry? A personal perspective on the Gawler program.

PMID- 22621157
TI  - Gender differences in endurance performance by elite cross-country skiers are
      influenced by the contribution from poling.
AB  - Greater gender differences have been found in exercise modes where the upper body
      is involved. Therefore, the present study investigated the influence of poling on
      gender differences in endurance performance by elite cross-country skiers.
      Initially, the performance of eight male and eight female sprint skiers was
      compared during four different types of exercise involving different degrees of
      poling: double poling (DP), G3 skating, and diagonal stride (DIA) techniques
      during treadmill roller skiing, and treadmill running (RUN). Thereafter, DP was
      examined for physiological and kinematic parameters. The relative gender
      differences associated with the DP, G3, DIA and RUN performances were
      approximately 20%, 17%, 14%, and 12%, respectively. Thus, the type of exercise
      exerted an overall effect on the relative gender differences (P < 0.05). In
      connection with DP, the men achieved 63%, 16%, and 8% higher VO2peak than the
      women in absolute terms and with normalization for total and fat-free body mass
      (all P < 0.05). The DP VO2peak in percentage of VO2max in RUN was higher in men
      (P < 0.05). The gender difference in DP peak cycle length was 23% (P < 0.05). In
      conclusion, the present investigation demonstrates that the gender difference in
      performance by elite sprint skiers is enhanced when the contribution from poling
      increases. 

PMID- 22621158
TI  - Effects of structure variation on solution properties of hydrotropes: phenyl
      versus cyclohexyl chain tips.
AB  - The physicochemical behavior of the phenyl-n-alkanoate (PhenCx) and cyclohexyl-n
      alkanoate (CyclohexCx) series has been investigated, supporting previous work on
      the understanding of hydrotropes (Hopkins Hatzopoulos, M.; Eastoe, J.; Dowding,
      P.J.; Rogers, S. E.; Heenan, R.; Dyer, R. Langmuir2011, 27, 12346-12353).
      Electrical conductivity, surface tension, (1)H NMR, and small-angle neutron
      scattering (SANS) were used to study adsorption and aggregation in terms of
      critical aggregation concentration (cac). The PhenCx series exhibited very
      similar d log(cac)/dn to n-alkylbenzoates (CnBenz), exhibiting two branches of
      behavior, with a common inflection point at four linear carbons, whereas the
      CyclohexCx series showed no break point. Electrical conductivity and (1)H NMR
      concentration scans indicate a difference in physicochemical behavior between
      higher and lower homologues in both the PhenCx and CyclohexCx series. Surface
      tension measurements with compounds belonging to either group gave typical Gibbs
      adsorption profiles, having d log(cac)/dn curves consistent with limiting
      headgroup areas in the region of (35-55 A(2)) indicating monolayer formation.
      SANS profiles showed no evidence for aggregates below the electrical conductivity
      determined cac values, inferring an "on-off" mode of aggregation. Analyses of
      SANS profiles was consistent with charged ellipsoidal aggregates, persisting from
      lower through to higher homologues in both the PhenCx and CyclohexCx series.

PMID- 22621159
TI  - Nitric oxide promotes MPK6-mediated caspase-3-like activation in cadmium-induced
      Arabidopsis thaliana programmed cell death.
AB  - Nitric oxide (NO), a vital cell-signalling molecule, has been reported to
      regulate toxic metal responses in plants. This work investigated the effects of
      NO and the relationship between NO and mitogen-activated protein kinase (MAPK) in
      Arabidopsis (Arabidopsis thaliana) programmed cell death (PCD) induced by cadmium
      (Cd(2+) ) exposure. With fluorescence resonance energy transfer (FRET) analysis,
      caspase-3-like protease activation was detected after Cd(2+)  treatment. This was
      further confirmed with a caspase-3 substrate assay. Cd(2+) -induced caspase-3
      like activity was inhibited in the presence of the NO-specific scavenger 2-(4
      carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), suggesting
      that NO mediated caspase-3-like protease activation under Cd(2+)  stress
      conditions. Pretreatment with cPTIO effectively inhibited Cd(2+) -induced MAPK
      activation, indicating that NO also affected the MAPK pathway. Interestingly,
      Cd(2+) -induced caspase-3-like activity was significantly suppressed in the mpk6
      mutant, suggesting that MPK6 was required for caspase-3-like protease activation.
      To our knowledge, this is the first demonstration that NO promotes Cd(2+) 
      induced Arabidopsis PCD by promoting MPK6-mediated caspase-3-like activation.

PMID- 22621160
TI  - Effect of size, surface charge, and hydrophobicity of poly(amidoamine) dendrimers
      on their skin penetration.
AB  - The barrier functions of the stratum corneum and the epidermal layers present a
      tremendous challenge in achieving effective transdermal delivery of drug
      molecules. Although a few reports have shown that poly(amidoamine) (PAMAM)
      dendrimers are effective skin-penetration enhancers, little is known regarding
      the fundamental mechanisms behind the dendrimer-skin interactions. In this
      Article, we have performed a systematic study to better elucidate how dendrimers
      interact with skin layers depending on their size and surface groups. Franz
      diffusion cells and confocal microscopy were employed to observe dendrimer
      interactions with full-thickness porcine skin samples. We have found that smaller
      PAMAM dendrimers (generation 2 (G2)) penetrate the skin layers more efficiently
      than the larger ones (G4). We have also found that G2 PAMAM dendrimers that are
      surface-modified by either acetylation or carboxylation exhibit increased skin
      permeation and likely diffuse through an extracellular pathway. In contrast,
      amine-terminated dendrimers show enhanced cell internalization and skin retention
      but reduced skin permeation. In addition, conjugation of oleic acid to G2
      dendrimers increases their 1-octanol/PBS partition coefficient, resulting in
      increased skin absorption and retention. Here we report that size, surface
      charge, and hydrophobicity directly dictate the permeation route and efficiency
      of dendrimer translocation across the skin layers, providing a design guideline
      for engineering PAMAM dendrimers as a potential transdermal delivery vector.

PMID- 22621161
TI  - Novel agents derived from the currently approved treatments for MM: novel
      proteasome inhibitors and novel IMIDs.
AB  - INTRODUCTION: Several novel proteasome inhibitors (PIs) and immunomodulatory
      agents (IMIDs) with similar, but not exactly the same, mechanisms of action than
      their predecessors have been developed in the last years with three different
      aims: to increase the efficacy; to overcome the resistance and to exhibit a
      better toxicity profile. AREAS COVERED: This review summarizes the mechanism of
      action of novel PIs (carfilzomib, ONX-0912, MLN-9708, marizomib and CEP-18770)
      and IMIDs (pomalidomide), stressing the similarities and differences with their
      parental drugs. It also reviews their most updated clinical results. A search of
      the recent literature in published papers and abstracts from the most important
      oncology scientific meetings (ASCO and ASH) has been performed. EXPERT OPINION:
      Novel PIs and IMIDs show clinical activity as single agents and in combination
      with dexamethasone, with similar or even higher efficacy than their predecessors;
      moreover, they may even overcome resistance to their parental drugs, indicating
      that there are some differences in their mechanisms of action and resistance. The
      investigation of these mechanisms of resistance and ways to overcome it would
      allow the optimization of the sequential use of these agents, and the design of
      novel therapeutic strategies and more appropriate scientifically based
      combinations.

PMID- 22621162
TI  - Effect of silver diamine fluoride on microtensile bond strength to dentin.
AB  - The aim of this in vitro study was to investigate the effect of the cariostatic
      and preventive agent silver diamine fluoride (SDF) on the microtensile bond
      strength of resin composite to dentin. Forty-two caries-free, extracted molars
      were flattened occlusally and apically using a diamond saw, and the exposed
      occlusal dentin was polished with a series of silicon carbide papers, all under
      water irrigation. The teeth were then randomly divided into six groups of seven
      teeth each that were treated as follows: 1) Peak SE self-etch bonding agent; 2)
      12% SDF + Peak SE; 3) 38% SDF + Peak SE; 4) Peak LC etch-and-rinse bonding agent;
      5) 12% SDF + Peak LC; and 6) 38% SDF + Peak LC. Four-millimeter buildups of
      Amelogen Plus were incrementally placed on all teeth; after a 24-hour storage
      period in distilled water, the specimens were sectioned perpendicular to the
      adhesive interface to produce beams of cross-sectional surface area measuring
      approximately 1 mm(2). The beams were placed on a microtensile testing machine,
      which utilized a single-speed pump motor and force gauge at 20 kgf * 0.01 second
      to record maximum tensile force before failure occurred. Two-way analysis of
      variance and post hoc Tukey tests were performed to compare the effects of the
      SDF on microtensile bond strength, with statistical significance set at alpha =
      0.05. None of the experimental groups treated with different concentrations of
      SDF showed a significant difference in bond strength compared to the control
      groups, and there was no significant difference in bond strength between self
      etch and etch-and-rinse groups. However, the effect of SDF on self-etch bonded
      teeth compared to etch-and-rinse bonded teeth was statistically significant
      (p=0.0363), specifically at the 12% concentration. SDF does not adversely affect
      the bond strength of resin composite to noncarious dentin.

PMID- 22621164
TI  - Fiber-reinforced framework in conjunction with porcelain veneers for the esthetic
      replacement of a congenitally missing maxillary lateral incisor: a case study.
AB  - This article presents a case of a congenitally missing right maxillary lateral
      incisor and the contralateral incisor with discolored composite resin
      restorations. The technique of fiber reinforcement in conjunction with porcelain
      veneers was used to provide a satisfactory outcome for the patient. The key
      learning points of the article are the following: proper diagnosis, treatment
      plan and appropriate utilization of materials are mandatory for a successful
      result.

PMID- 22621163
TI  - One-year clinical evaluation of composite restorations in posterior teeth: effect
      of adhesive systems.
AB  - This clinical study assessed the performance of posterior composite resins
      applied with the AdperTM Single Bond Plus (SB) and AdperTM Scotchbond SE (SE)
      adhesive systems and FiltekTM Supreme Plus composite resin, using modified US
      Public Health Service criteria. A total of 97 restorations were placed in
      posterior teeth by two calibrated operators. Application of the materials
      followed manufacturers' instructions. The restorations were evaluated by two
      examiners at baseline and after one year. Statistical analyses were conducted
      using the proportion test at a significance level of 5% (p<0.05). All the
      restorations evaluated (ie, 100%) received an alpha rating for the criteria of
      marginal discoloration and marginal integrity at baseline. At one year, for
      marginal discoloration, 64.6% of SB and 61.2% of SE received an alpha rating. For
      marginal integrity, 72.9% of SB and 77.6% of SE received an alpha rating. The
      other restorations received bravo ratings for both criteria. None of the teeth
      that received the restorative systems presented caries lesions around the
      restorations. A total of eight teeth presented postoperative sensitivity one week
      after baseline, five with SB and three with SE; the symptom had disappeared one
      year later. One year later, composite resin restorations using either adhesive
      system showed satisfactory clinical performance.

PMID- 22621165
TI  - Quantification of peroxide ion passage in dentin, enamel, and cementum after
      internal bleaching with hydrogen peroxide.
AB  - The aim of this study was to evaluate the amount of peroxide passage from the
      pulp chamber to the external enamel surface during the internal bleaching
      technique. Fifty bovine teeth were sectioned transversally 5 mm below the cemento
      enamel junction (CEJ), and the remaining part of the root was sealed with a 2-mm
      layer of glass ionomer cement. The external surface of the samples was coated
      with nail varnish, with the exception of standardized circular areas (6-mm
      diameter) located on the enamel, exposed dentin, or cementum surface of the
      tooth. The teeth were divided into three experimental groups according to exposed
      areas close to the CEJ and into two control groups (n=10/group), as follows: GE,
      enamel exposure area; GC, cementum exposed area; GD, dentin exposed area;
      Negative control, no presence of internal bleaching agent and uncoated surface;
      and Positive control, pulp chamber filled with bleaching agent and external
      surface totally coated with nail varnish. The pulp chamber was filled with 35%
      hydrogen peroxide (Opalescence Endo, Ultradent). Each sample was placed inside of
      individual flasks with 1000 MUL of acetate buffer solution, 2 M (pH 4.5). After
      seven days, the buffer solution was transferred to a glass tube, in which 100 MUL
      of leuco-crystal violet and 50 MUL of horseradish peroxidase were added,
      producing a blue solution. The optical density of the blue solution was
      determined by spectrophotometer and converted into microgram equivalents of
      hydrogen peroxide. Data were submitted to Kruskal-Wallis and Dunn-Bonferroni
      tests (alpha=0.05). All experimental groups presented passage of peroxide to the
      external surface that was statistically different from that observed in the
      control groups. It was verified that the passage of peroxide was higher in GD
      than in GE (p<0.01). The GC group presented a significantly lower peroxide
      passage than did GD and GE (p<0.01). It can be concluded that the hydrogen
      peroxide placed into the pulp chamber passed through the dental hard tissues,
      reaching the external surface and the periodontal tissue. The cementum surface
      was less permeable than were the dentin and enamel surfaces.

PMID- 22621166
TI  - Ceramic primer heat-treatment effect on resin cement/Y-TZP bond strength.
AB  - The purpose of this study was to evaluate the effect of different heat-treatment
      strategies for a ceramic primer on the shear bond strength of a 10
      methacryloyloxydecyl-dihydrogen-phosphate (MDP)-based resin cement to a yttrium
      stabilized tetragonal zirconia polycrystal (Y-TZP) ceramic. Specimens measuring
      4.5 * 3.5 * 4.5 mm(3) were produced from Y-TZP presintered cubes and embedded in
      polymethyl methacrylate (PMMA). Following finishing, the specimens were cleaned
      using an ultrasound device and distilled water and randomly divided into 10
      experimental groups (n=14) according to the heat treatment of the ceramic primer
      and aging condition. The strategies used for the experimental groups were: GC
      (control), without primer; G20, primer application at ambient temperature (20
      degrees C); G45, primer application + heat treatment at 45 degrees C; G79, primer
      application + heat treatment at 79 degrees C; and G100, primer application + heat
      treatment at 100 degrees C. The specimens from the aging groups were submitted to
      thermal cycling (6000 cycles, 5 degrees C/55 degrees C, 30 seconds per bath)
      after 24 hours. A cylinder of MDP-based resin cement (2.4 mm in diameter) was
      constructed on the ceramic surface of the specimens of each experimental group
      and stored for 24 hours at 37 degrees C. The specimens were submitted to a shear
      bond strength test (n=14). Thermal gravimetric analysis was performed on the
      ceramic primer. The data obtained were statistically analyzed by two-way analysis
      of variance and the Tukey test (alpha=0.05). The experimental group G79 without
      aging (7.23 +/- 2.87 MPa) presented a significantly higher mean than the other
      experimental groups without aging (GC: 2.81 +/- 1.5 MPa; G20: 3.38 +/- 2.21 MPa;
      G100: 3.96 +/- 1.57 MPa), showing no difference from G45 only (G45: 6 +/- 3.63
      MPa). All specimens of the aging groups debonded during thermocycling and were
      considered to present zero bond strength for the statistical analyses. In
      conclusion, heat treatment of the metal/zirconia primer improved bond strength
      under the initial condition but did not promote stable bonding under the aging
      condition.

PMID- 22621167
TI  - The optimal combination of cartilage source and apparatus for long-term in vitro
      chondrocyte viability analysis.
AB  - Most studies of long-term chondrocytes survival were for tissue banks. They
      showed a gradual reduction in the viable chondrocytes percentage as a function of
      time and ambient temperature, but the samples were harvested under optimal
      conditions. The aim of our study was to determine the most reliable combination
      of cartilage source and assay for the in vitro postmortem chondrocyte viability
      analysis in the conditions that imitate a dead body. Osteochondral cylinders were
      procured from femoral condyles and talar trochleas of three male donors and
      stored in the cell culture media at 4 +/- 2 degrees C and 23 +/- 2 degrees C. The
      samples were analyzed by a cell viability analyzer and a confocal laser scanning
      microscope (CLSM) initially 24-36 h after death and then in 4-week intervals. The
      results reconfirmed the significant influence of time (p = 0.0002), but not of
      the temperature (p = 0.237). The largest reproducibility was presented for the
      knee joint and the CLSM.

PMID- 22621169
TI  - Catalytic enantioselective protonation of nitronates utilizing an organocatalyst
      chiral only at sulfur.
AB  - The highly enantioselective protonation of nitronates formed upon the addition of
      alpha-substituted Meldrum's acids to terminally unsubstituted nitroalkenes is
      described. This work represents the first enantioselective catalytic addition of
      any type of nucleophile to this class of nitroalkenes. Moreover, for the
      successful implementation of this method, a new type of N-sulfinyl urea catalyst
      with chirality residing only at the sulfinyl group was developed, thereby
      enabling the incorporation of a diverse range of achiral diamine motifs. Finally,
      the Meldrum's acid addition products were readily converted to pharmaceutically
      relevant 3,5-disubstituted pyrrolidinones in high yield.

PMID- 22621170
TI  - Experimental quantification of anion-pi interactions in solution using neutral
      host-guest model systems.
AB  - Chemical intuition suggests that anions and pi-aromatic systems would repel each
      other. Typically, we think of cations as being attracted to electron-rich pi
      systems of aromatic rings, and the cation-pi interaction, a well-established
      noncovalent interaction, plays an important role in nature. Therefore the anion
      pi interaction can be considered the opposite of the cation-pi interaction.
      Computational studies of simple models of anion-pi interactions have provided
      estimates of the factors that govern the binding geometry and the binding energy,
      leading to a general consensus about the nature of these interactions. In order
      to attract an anion, the charge distribution of the aromatic system has to be
      reversed, usually through the decoration of the aromatic systems with strongly
      electron-withdrawing groups. Researchers have little doubt about the existence of
      attractive anion-pi interactions in the gas phase and in the solid state. The
      bonding energies assigned to anion-pi interactions from quantum chemical
      calculations and gas phase experiments are significant and compare well with the
      values obtained for cation-pi interactions. In solution, however, there are few
      examples of attractive anion-pi interactions. In this Account, I describe several
      examples of neutral molecular receptors that bind anions in solution either
      solely through anion-pi interactions or as a combination of anion-pi interactions
      and hydrogen bonding. In the latter cases, the strength of the anion-pi
      interaction is indirectly detected as a modulation of the stronger hydrogen
      bonding interaction (enforced proximity). The dissection of the energy
      contribution of the anion-pi interaction to the overall binding is complex, which
      requires the use of appropriate reference systems. This Account gives an overview
      the experimental efforts to determine the binding energies that can be expected
      from anion-pi interactions in solution with examples that center around the
      recognition of halides. The studies show that anion-pi interactions also exist in
      solution, and the free energy of binding estimated for these attractive
      interactions is less than 1 kcal/mol for each substituted phenyl groups. The
      quantification of anion-pi interactions in solution relies on the use of
      molecular recognition model systems; therefore researchers need to consider how
      the structure of the model system can alter the magnitude of the observed energy
      values. In addition, the recognition of anions in solution requires the use of
      salts (ion pairs) as precursors, which complicates the analysis of the titration
      data and the corresponding estimate of the binding strength. In solution, the
      weak binding energies suggest that anion-pi interactions are not as significant
      for the selective or enhanced binding of anions but offer potential applications
      in catalysis and transport within functional synthetic and biological systems.

PMID- 22621168
TI  - Testing physical models of passive membrane permeation.
AB  - The biophysical basis of passive membrane permeability is well-understood, but
      most methods for predicting membrane permeability in the context of drug design
      are based on statistical relationships that indirectly capture the key physical
      aspects. Here, we investigate molecular mechanics-based models of passive
      membrane permeability and evaluate their performance against different types of
      experimental data, including parallel artificial membrane permeability assays
      (PAMPA), cell-based assays, in vivo measurements, and other in silico
      predictions. The experimental data sets we use in these tests are diverse,
      including peptidomimetics, congeneric series, and diverse FDA approved drugs. The
      physical models are not specifically trained for any of these data sets; rather,
      input parameters are based on standard molecular mechanics force fields, such as
      partial charges, and an implicit solvent model. A systematic approach is taken to
      analyze the contribution from each component in the physics-based permeability
      model. A primary factor in determining rates of passive membrane permeation is
      the conformation-dependent free energy of desolvating the molecule, and this
      measure alone provides good agreement with experimental permeability measurements
      in many cases. Other factors that improve agreement with experimental data
      include deionization and estimates of entropy losses of the ligand and the
      membrane, which lead to size-dependence of the permeation rate.

PMID- 22621171
TI  - The relationship between bipolar disorder and type 2 diabetes: more than just co
      morbid disorders.
AB  - Type 2 diabetes mellitus (T2DM) rates are three times higher in patients with
      bipolar disorder (BD), compared to the general population. This is a major
      contributing factor to the elevated risk of cardiovascular mortality, the leading
      cause of death in bipolar patients. There may be shared pathophysiology linking
      the two disorders, including hypothalamic-pituitary-adrenal and mitochondrial
      dysfunction, common genetic links, and epigenetic interactions. Life-style,
      phenomenology of bipolar symptoms, and adverse effects of pharmacotherapy may be
      contributing factors. Patients with BD and T2DM have a more severe course of
      illness and are more refractory to treatment. Control of their diabetes is poorer
      when compared to diabetics without BD, and an existing disparity in medical care
      may be partly responsible. Glucose abnormalities in bipolar patients need to be
      screened for and treated. Metformin appears to have the best benefit/risk ratio,
      and the dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor
      agonists and analogues also appear promising, although these agents have not been
      specifically studied in populations with mood disorders. Physicians need to be
      aware of the increased risk for T2DM and cardiovascular disease in bipolar
      patients, and appropriate prevention, screening, case finding, and treatment is
      recommended.

PMID- 22621172
TI  - Epidemiology of dermatophytosis in junior combat and non-combat sports
      participants.
AB  - Participation in competitive sports is popular and widely encouraged worldwide.
      Herein, we investigated 252 male and 67 female sports players, aged 16.4 +/- 1.3
      years, active in 15 different types of combat (n = 143) and non-combat (n = 176)
      sports. Of the 319 participants in this study, 11 (3.5%) players, including six
      wrestlers, four football players and one handball player, all of whom were men,
      harboured dermatophytic fungi. Briefly, Trichophyton tonsurans was present in
      three athletes, who were scalp carriers of the fungus. Furthermore, T. rubrum
      (4), T. interdigitale (3) and Arthroderma simii (1) were recovered from eight
      participants with tinea inguinalis (4), tinea pedis (2) or both (1). One patient
      was a trunk carrier of concomitant tinea pedis. All dermatophytic fungi were
      identified using both direction sequence of the rDNA regions spanning the
      internal transcribed spacers (ITS1 and ITS2) and 5.8 rRNA gene. Although sports
      active individuals are active and sweat more, we observed a low prevalence of
      dermatophytosis, both in combat (5.2%) and non-combat sports participants (3.4%)
      (P > 0.05). However, dermatophyte infections require more attention and
      appropriate management to eradicate the infection and to prevent possible
      outbreaks. This study also documents the first case of zoophilic A. simii in
      Turkey.

PMID- 22621173
TI  - Evaluation of the effects of cryopreservation on viability, proliferation and
      colony formation of human spermatogonial stem cells in vitro culture.
AB  - Proliferation of spermatogonial stem cells (SSCs) in vitro system is very
      important. It can enhance SSCs numbers for success of transplantation and
      treatment of infertility in cancer patients. In this study, testicular cells that
      obtained from azoospermia patients (n=8) by enzymatic digestion were
      cryopreserved at the beginning and after 2 weeks of culture. Then, frozen-thawed
      SSCs were co-cultured on fresh Sertoli cells (experimental group 1), and frozen
      thawed Sertoli cells (experimental group 2) for another 3 weeks. In control
      group, fresh SSCs were co-cultured on fresh Sertoli cells. Viability rate after
      enzymatic digestion was 93.4%+/-5.0. Frozen-thawed testicular cells after 2 weeks
      of culture had a significantly (P<0.05) higher percentage of living cells
      compared to frozen-thawed testicular cells at the beginning of culture (59.2+/
      7.05 and 46.3+/-8.40 respectively). The number of colonies in the experimental
      group 1 was significantly higher than experimental group 2 (19.6+/-2.8 and 8.33+/
      1.5, respectively, P<0.05). The diameter of the colonies in the experimental
      group 1 was significantly higher than control and experimental group 2 (P<0.05)
      after 3 weeks of culture (269.7+/-52.1, 204.34+/-24.1 and 112.52+/-23.5 MUm,
      respectively). Cryopreservation technique will raise the possibility of banking
      SSCs for men who have a cancer-related illness and waiting for radiotherapy
      and/or chemotherapy.

PMID- 22621174
TI  - Emotional states of love moderate the association between catecholamines and
      female sexual responses in the laboratory.
AB  - INTRODUCTION: Research suggests that there are three interrelated, yet distinct,
      emotion-motivation brain systems for human love (lust, romantic love, and
      attachment), each associated with a unique catecholaminergic and hormonal
      profile. Of interest for the current study are norepinephrine (NE) and dopamine
      (DA), which have a hypothesized connection with romantic love. As NE and DA are
      also known to facilitate sexual arousal, it is plausible that NE and DA may have
      a greater positive association with the sexual arousal responses of women in
      romantic love compared with women in lust. AIM: This study investigated if the
      effects of NE and DA activity on sexual arousal responses would differ depending
      on emotion-motivation state (Lust or Romantic). MAIN OUTCOME MEASURES:
      Physiological sexual arousal was assessed by photoplethysmography and subjective
      sexual arousal was assessed with a participant-controlled lever. METHODS:
      Seventeen women were included in the Lust group and 29 in the Romantic group. All
      participants provided a urine sample (to assess NE and DA) and completed a
      psychophysiological assessment. RESULTS: Elevated NE was positively and
      significantly associated with greater subjective and physiological sexual arousal
      for the Lust group, but not for the Romantic group. Similarly, elevated DA was
      positively and significantly associated with greater subjective sexual arousal
      for the Lust group, but not for the Romantic group. CONCLUSIONS: The sexual
      arousal responses of women in the Lust group, but not in the Romantic group, were
      positively and significantly associated with elevated NE and DA. It is feasible
      that, when women are seeking a partner (Lust), NE and DA may facilitate attention
      toward sexually relevant stimuli.

PMID- 22621175
TI  - Increased bovine Tim-3 and its ligand expressions during bovine leukemia virus
      infection.
AB  - The immunoinhibitory receptor T cell immunoglobulin domain and mucin domain-3
      (Tim-3) and its ligand, galectin-9 (Gal-9), are involved in the immune evasion
      mechanisms for several pathogens causing chronic infections. However, there is no
      report concerning the role of Tim-3 in diseases of domestic animals. In this
      study, cDNA encoding for bovine Tim-3 and Gal-9 were cloned and sequenced, and
      their expression and role in immune reactivation were analyzed in bovine leukemia
      virus (BLV)-infected cattle. Predicted amino acid sequences of Tim-3 and Gal-9
      shared high homologies with human and mouse homologues. Functional domains,
      including tyrosine kinase phosphorylation motif in the intracellular domain of
      Tim-3 were highly conserved among cattle and other species. Quantitative real
      time PCR analysis showed that bovine Tim-3 mRNA is mainly expressed in T cells
      such as CD4+ and CD8+ cells, while Gal-9 mRNA is mainly expressed in monocyte and
      T cells. Tim-3 mRNA expression in CD4+ and CD8+ cells was upregulated during
      disease progression of BLV infection. Interestingly, expression levels for Tim-3
      and Gal-9 correlated positively with viral load in infected cattle. Furthermore,
      Tim-3 expression level closely correlated with up-regulation of IL-10 in infected
      cattle. The expression of IFN-gamma and IL-2 mRNA was upregulated when PBMC from
      BLV-infected cattle were cultured with Cos-7 cells expressing Tim-3 to inhibit
      the Tim-3/Gal-9 pathway. Moreover, combined blockade of the Tim-3/Gal-9 and PD
      1/PD-L1 pathways significantly promoted IFN-gamma mRNA expression compared with
      blockade of the PD-1/PD-L1 pathway alone. These results suggest that Tim-3 is
      involved in the suppression of T cell function during BLV infection.

PMID- 22621176
TI  - The vinylogous aldol reaction of unsaturated esters and enolizable aldehydes
      using the novel Lewis acid aluminum tris(2,6-di-2-naphthylphenoxide).
AB  - The synthesis of the novel Lewis acid, aluminum tris(2,6-di-2-naphthylphenoxide)
      (ATNP), and its use in the vinylogous aldol reaction between methyl crotonate and
      enolizable aldehydes are described. ATNP is related to Yamamoto's Lewis acid,
      aluminum tris(2,6-diphenylphenoxide) (ATPH), but the 2-naphthyl groups more
      effectively block the alpha-position of aldehydes, enabling the selective
      enolization of crotonate esters in the presence of enolizable aldehydes.
      Vinylogous aldol reactions then proceed smoothly and in high yields with a
      variety of substrates.

PMID- 22621177
TI  - Effect of fluorine ions on 2.7 MUm emission in Er3+/Nd(3+)-codoped
      fluorotellurite glass.
AB  - The 2.7 MUm emission properties of Er(3+)/Nd(3+)-codoped fluorotellurite glasses
      were investigated in the present work. The thermal stability, refractive index,
      absorption and transmission spectra, and emission spectra were measured and
      investigated. The 2.7 MUm emission in Er(3+)/Nd(3+)-codoped fluorotellurite
      glasses was enhanced with the increase of fluorine ions. The Judd-Ofelt analysis
      based on absorption spectra was performed in order to determine the Judd-Ofelt
      intensity parameters Omegat (t = 2, 4, 6), spontaneous emission probability,
      radiative lifetime and branching ratios of Er(3+):(4)I(11/2) -> (4)I(13/2)
      transition. It is found that the Er(3+)/Nd(3+)-codoped fluorotellurite glass
      possesses a lower spontaneous transition probability A (58.95 s(-1)) but a higher
      branching ratio beta (15.72%) corresponding to the stimulated emission of
      Er(3+):(4)I(11/2) -> (4)I(13/2) transition. Additionally, the transmittance was
      also tested and reached a maximum when the molar concentration of ZnF(2) is 15%.
      The presence of fluorine ions greatly decreases the population of OH(-) groups,
      which affects the 2.7 MUm emission effectively by means of decreasing the rate of
      energy transfer to impurities (e.g., OH(-) groups).

PMID- 22621178
TI  - Aqueous suspensions of GdPO4 nanorods: a paramagnetic mineral liquid crystal.
AB  - Colloidal suspensions of rod-like nanoparticles are well-known to readily form
      liquid-crystalline phases. Using mineral nanoparticles for this purpose may
      impart their liquid-crystalline suspensions with original physical properties. We
      synthesized GdPO(4) nanorods whose aqueous suspensions spontaneously organize in
      a nematic phase at high concentrations. The nematic phase is very well aligned by
      small magnetic fields, and the isotropic phase displays a very large field
      induced birefringence. Moreover, the nanorods migrate to regions of high magnetic
      field. On the basis of magnetization measurements, we show that this unusual
      behavior is due to the fact that GdPO(4) nanorods are actually paramagnetic. Such
      a paramagnetic mineral liquid crystal, easily synthesized and little sensitive to
      temperature, may be an interesting alternative to organometallic thermotropic
      liquid crystals for applications where magnetic field alignment would be more
      suitable than electric field alignment.

PMID- 22621179
TI  - Overlapping profiles of Abeta peptides in the Alzheimer's disease and
      pathological aging brains.
AB  - INTRODUCTION: A hallmark of Alzheimer's disease (AD) is the presence of senile
      plaques composed of aggregated amyloid beta (Abeta) peptides. Pathological aging
      (PA) is a postmortem classification that has been used to describe brains with
      plaque pathology similar in extent to AD, minimal cortical tau pathology, and no
      accompanying history of cognitive decline in the brain donor prior to death. PA
      may represent either a prodromal phase of AD, a benign form of Abeta
      accumulation, or inherent individual resistance to the toxic effects of Abeta
      accumulation. To attempt to distinguish between these possibilities we have
      systematically characterized Abeta peptides in a postmortem series of PA, AD and
      non-demented control (NDC) brains. METHODS: Abeta was sequentially extracted with
      tris buffered saline (TBS), radioimmunoprecipitation buffer (RIPA), 2% sodium
      dodecyl sulfate (SDS) and 70% formic acid (FA) from the pre-frontal cortex of 16
      AD, eight PA, and six NDC patients. These extracts were analyzed by 1) a panel of
      Abeta sandwich ELISAs, 2) immunoprecipitation followed by mass spectrometry
      (IP/MS) and 3) western blotting. These studies enabled us to asses Abeta levels
      and solubility, peptide profiles and oligomeric assemblies. RESULTS: In almost
      all extracts (TBS, RIPA, 2% SDS and 70% FA) the average levels of Abeta1-40,
      Abeta1-42, Abeta total, and Abetax-42 were greatest in AD. On average, levels
      were slightly lower in PA, and there was extensive overlap between Abeta levels
      in individual PA and AD cases. The profiles of Abeta peptides detected using
      IP/MS techniques also showed extensive similarity between the PA and AD brain
      extracts. In select AD brain extracts, we detected more amino-terminally
      truncated Abeta peptides compared to PA patients, but these peptides represented
      a minor portion of the Abeta observed. No consistent differences in the Abeta
      assemblies were observed by western blotting in the PA and AD groups.
      CONCLUSIONS: We found extensive overlap with only subtle quantitative differences
      between Abeta levels, peptide profiles, solubility, and SDS-stable oligomeric
      assemblies in the PA and AD brains. These cross-sectional data indicate that
      Abeta accumulation in PA and AD is remarkably similar. Such data would be
      consistent with PA representing a prodromal stage of AD or a resistance to the
      toxic effects of Abeta.

PMID- 22621180
TI  - OnabotulinumtoxinA dose-ranging study for hyperdynamic perioral lines.
AB  - BACKGROUND: Few dosing data on onabotulinumtoxinA to treat hyperdynamic perioral
      lines (POLs) are available. Studying onabotulinumtoxinA in controlled settings is
      beneficial to treating a hyperfunctional orbicularis oris. OBJECTIVE: To compare
      the dose-response relationship of two doses of onabotulinumtoxinA in hyperdynamic
      POLs. METHODS: Female subjects (N = 60) received injections of onabotulinumtoxinA
      at four sites totaling 7.5 U or 12.0 U. Subjects returned at weeks 2, 4, 8, 12,
      16, and 20. POL severity and total lip satisfaction (TLS) were assessed at all
      visits. RESULTS: Investigator-assessed POL severity was reduced through week 20
      for 12.0 U (p < .01). POL reduction for 7.5 U persisted until week 16 (p < .05).
      Responder rates did not differ until week 12 (12.0 U, 77%; 7.5 U, 36%; p = .003).
      Subject-assessed TLS was improved (p < .05) at all time points for both groups
      except at week 20 (12.0 U; p = .06). Most adverse events (AEs) were mild to
      moderate in severity and typical for onabotulinumtoxinA treatment in the lips,
      and the incidence was dose-dependent. CONCLUSION: OnabotulinumtoxinA provides
      significant reductions in POL severity and high levels of subject satisfaction.
      Lack of dose response and fewer AEs suggest that treatment of hyperdynamic POLs
      with 7.5 U appears adequate for up to 16 weeks.

PMID- 22621181
TI  - Gallium-67-labeled lactam bridge-cyclized alpha-MSH peptides with enhanced
      melanoma uptake and reduced renal uptake.
AB  - The purpose of this study was to examine the melanoma targeting and
      pharmacokinetic properties of (67)Ga-DOTA-GGNle-CycMSHhex {(67)Ga-1,4,7,10
      tetraazacyclononane-1,4,7,10-tetraacetic acid-Gly-Gly-Nle-c[Asp-His-DPhe-Arg-Trp
      Lys]-CONH2} and (67)Ga-NOTA-GGNle-CycMSHhex {(67)Ga-1,4,7-triazacyclononane-1,4,7
      triacetic acid-Gly-Gly-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH2} and compare with
      (67)Ga-DOTA-GlyGlu-CycMSH {(67)Ga-DOTA-Gly-Glu-c[Lys-Nle-Glu-His-DPhe-Arg-Trp-Gly
      Arg-Pro-Val-Asp]} we previously reported. DOTA-GGNle-CycMSHhex and NOTA-GGNle
      CycMSHhex were synthesized using fluorenylmethyloxy carbonyl (Fmoc) chemistry.
      The melanocortin-1 (MC1) receptor binding affinity of NOTA-GGNle-CycMSHhex was
      determined in B16/F1 melanoma cells and compared with DOTA-GGNle-CycMSHhex. The
      melanoma targeting and pharmacokinetic properties of (67)Ga-NOTA-GGNle-CycMSHhex
      and (67)Ga-DOTA-GGNle-CycMSHhex were determined in B16/F1 melanoma-bearing C57
      mice. NOTA-GGNle-CycMSHhex and DOTA-GGNle-CycMSHhex displayed comparable MC1
      receptor binding affinities (1.6 vs 2.1 nM) in B16/F1 melanoma cells. Both (67)Ga
      NOTA-GGNle-CycMSHhex and (67)Ga-DOTA-GGNle-CycMSHhex exhibited dramatically
      enhanced melanoma uptake and reduced renal uptake than (67)Ga-DOTA-GlyGlu-CycMSH
      in B16/F1 melanoma-bearing C57 mice. Furthermore, (67)Ga-NOTA-GGNle-CycMSHhex
      exhibited more favorable radiolabeling conditions (>85% radiolabeling yields
      started at 37  degrees C), as well as higher tumor/kidney uptake ratios than
      (67)Ga-DOTA-GGNle-CycMSHhex at 0.5, 2, and 24 h postinjection. High melanoma
      uptake coupled with low renal uptake highlighted the potential of (67)Ga-NOTA
      GGNle-CycMSHhex for melanoma imaging and therapy. 

PMID- 22621182
TI  - IL-27 acts as a priming signal for IL-23 but not IL-12 production on human
      antigen-presenting cells.
AB  - IL-27 belongs to the IL-12 family of cytokines and has been described not only to
      support T-cell polarization along the Th1 lineage, but also to induce important
      anti-inflammatory responses in later phases of inflammation. We and others have
      previously shown that the cytokine IL-27 has an important impact on the chronic
      manifestation of inflammatory skin diseases. Thus, the aim of this study was to
      specify the effects of IL-27 on the human antigen-presenting cell (APC) subtype
      inflammatory dendritic epidermal cells (IDEC), which are known to play an
      important role in eczema. IDEC and blood-derived human macrophages were generated
      from human peripheral blood and stimulated with IL-27. Functional responses of
      the cells were analysed by intracellular cytokine staining, ELISA and
      FlowCytomix. IL-27 was found to be the only IL-12 family member that acts on
      human APC as a priming signal for IL-23 but not IL-12 production. We confirmed
      for macrophages that IL-27 limits lipopolysaccharide-induced IL-10 production and
      detected the same tendency for IDEC. Furthermore, we showed that this also
      applies to CD40L-induced IL-10 expression in both investigated human APC subsets.
      We demonstrate that IL-27 exerts pro-inflammatory effects on human APC in
      particular in the context of a range of bacterial-derived TLR ligands. Hence, our
      study builds upon the idea that IL-27 exerts a pro-inflammatory effect on innate
      immune and tissue-resident cells and may drive eczematous reaction - in
      particular in the context of bacterial superinfection - towards a chronic phase.

PMID- 22621183
TI  - Increased frequencies of IL-31-producing T cells are found in chronic atopic
      dermatitis skin.
AB  - Interleukin (IL)-31 has been associated with pruritus, a characteristic feature
      of atopic dermatitis (AD). Local T cell responses may be responsible for the
      increased level of IL-31 mRNA observed in AD. We investigated the frequency of IL
      31-producing T cells in AD lesions, as well as their cytokine profile. T cells
      were isolated from chronic AD lesions, autologous blood and healthy donor skin.
      Intracellular expression of IL-31, IFN-gamma, IL-13, IL-17 and IL-22 was measured
      using flow cytometry. T cells from AD lesions contained significantly higher
      percentages of IL-31-producing T cells compared to autologous blood and donor
      skin. Many IL-31-producing T cells co-produced IL-13 and to lesser extent IL-22,
      but rarely IFN-gamma or IL-17. A substantial part of the IL-31-producing T cells
      did not co-produce any of the other cytokines and could therefore not be linked
      to any of the known functionally different T cell subsets. The T cell infiltrates
      were also relatively enriched for Th2/Tc2 and Th22/Tc22 cells, while frequencies
      of Th1/Tc1 and Th17 cells were decreased. This is the first report describing the
      detection of IL-31 at protein level in skin-infiltrating T cells. We show here
      that T cells in chronic AD skin produce IL-31 and that AD lesions contain
      increased levels of these IL-31-producing T cells. This suggests that a
      substantial part of previously reported increased IL-31 mRNA levels in AD skin is
      T cell derived and that these cells may be involved in the pathogenesis of AD.

PMID- 22621184
TI  - Role of ADAM-15 in wound healing and melanoma development.
AB  - Proteins of the a disintegrin and metalloprotease (ADAM) family are transmembrane
      proteins involved in ectodomain shedding and in cellular interactions. In skin,
      ADAM-15 is detected in the epidermis and dermal vascular structures by
      immunolocalization. Expression is also detected in isolated fibroblast,
      keratinocytes and endothelial cells in culture. Despite high expression of ADAM
      15 throughout the wound repair process, wound healing experiments in vivo
      revealed a dispensable role of ADAM-15 for the healing process. No alterations in
      wound closure, re-epithelialization, contraction, scar formation and angiogenesis
      were detected in animals carrying ADAM-15-/- deletion. When analysing melanoma
      development by grafting melanoma cells into the flank of ADAM-15-/-, no
      significant alteration in tumor growth was detected. However, at later stages,
      melanomas in the ADAM-15-/- animals were smaller than those grown in WT animals.
      At all time points, no significant differences in vascularization of the
      peritumoral stroma and tumors were detected. Interestingly, we could detect a
      reduced number of metastasized lungs and lymph nodes in ADAM-15-/- animals as
      compared to control littermate mice. In conclusion, our study indicated that ADAM
      15 is dispensable for cutaneous wound healing and B16F1 melanoma growth, but
      significantly contributes to metastasis formation.

PMID- 22621185
TI  - Leucocyte scintigraphy with 111In-oxine for assessment of cell trafficking after
      extracorporeal photopheresis.
AB  - Extracorporeal photopheresis (ECP) is an established therapy for transplant
      rejection, graft-versus-host disease (GvHD) after allogeneic stem cell
      transplantation, cutaneous T-cell lymphoma and systemic autoimmune disorders such
      as systemic sclerosis. Knowledge regarding the in vivo behaviour of the cells
      after reinfusion is very limited. The aim of this prospective study was to
      investigate the path of 8-MOP-/UVA-exposed radiolabelled cells after ECP
      treatment and reinfusion. In this prospective single-centre study, peripheral
      blood mononuclear cells (PBMC) and neutrophils of 10 patients undergoing ECP as
      part of their regular treatment were labelled separately with (111) In-oxine
      after exposure to 8-MOP/UVA and prior to reinfusion. The fate of the labelled
      leucocytes was monitored at 10 min, 3.5 and 24 h following reinfusion with whole
      body scintigraphy. Comparison of distribution patterns showed that PBMC and
      neutrophils have different kinetic patterns after intravenous reinjection. The
      most prominent difference was immediate retention of PBMC but not of neutrophils
      in the lungs corresponding to a signal three times more intense. After 24 h, more
      than 80% of both cell populations could be detected in liver and spleen. By means
      of a novel tool allowing for tracking of 8-MOP-/UVA-exposed leucocytes in ECP, we
      could show that organ-specific homing of leucocytes after ECP can be visualized
      in vivo and that migration patterns differ between PBMC and neutrophils. Based on
      our results, further studies should (i) extend the morphometric studies described
      here to specific ECP-responsive conditions and (ii) functionally address the
      interaction of ECP-modified PBMC with pulmonary tissue in experimental models.

PMID- 22621186
TI  - Dietary sphingolipids improve skin barrier functions via the upregulation of
      ceramide synthases in the epidermis.
AB  - Sphingolipids are ubiquitous in eukaryotic organisms and are significant
      components in foods. It has been reported that treatment with sphingolipids
      prevents colon cancer, improves skin barrier function and suppresses inflammatory
      responses. However, the mechanisms for those effects of dietary sphingolipids are
      not well understood. In this study, to investigate the effects of dietary
      glucosylceramide (GluCer) and sphingomyelin (SM) on skin function, we
      characterized the recovery of skin barrier function and the change in
      sphingolipid metabolism-related enzymes in the epidermis using a special Mg
      deficient diet-induced atopic dermatitis-like skin and tape-stripping damaged
      skin murine models. Our results show that dietary GluCer and SM accelerate the
      recoveries of damaged skin barrier functions. Correspondingly, dietary
      sphingolipids significantly upregulated the expression of ceramide synthases 3
      and 4 in the epidermis of the atopic dermatitis-like skin model (P < 0.05). In
      the case of cultured cells, the expression of ceramide synthases 2-4 in normal
      human foreskin keratinocytes was significantly upregulated by treatment with
      0.001-0.1 MUm sphingoid bases (sphinganine, sphingosine and trans-4,cis-8
      sphingadienine) (P < 0.05). These results suggest that the effects of dietary
      sphingolipids might be due to the activation of ceramide synthesis in the skin,
      rather than the direct reutilization of dietary sphingolipids. Our findings
      provide a novel insight into the mechanisms of the skin barrier improving effect
      and a more comprehensive understanding of dietary sphingolipids.

PMID- 22621187
TI  - Cutaneomucosal venous malformations are linked to the TIE2 mutation in a large
      Chinese family.
AB  - Mutations in TIE2/TEK gene have been identified as the major cause for
      cutaneomucosal venous malformations (VMCM) that were previously reported to occur
      in Caucasian families. We report here for the first time a Chinese VMCM family of
      19 affected individuals in five generations with multiple vascular lesions on
      their oral mucosa and extremities. Histological analyses showed that the lesions
      comprised of irregular vascular spaces with a continuous layer of endothelial
      cells and variable smooth muscle cells. Although these VMCM characters were
      consistent with those in Caucasian families, difference was observed in
      hyperplastic SMC layer and vascular walls. Haplotype analyses and DNA sequencing
      indicated that both the mutation-associated haplotype and a R849W (c.2545C>T)
      change of the TIE2 gene cosegregated perfectly with the VMCM phenotype. This
      result suggested that, like those in Caucasian families, the R849W mutation in
      TIE2 could be one of the major causes for VMCM in Asian families.

PMID- 22621188
TI  - Wool-derived keratin stimulates human keratinocyte migration and types IV and VII
      collagen expression.
AB  - Keratinocyte migration is essential for wound repair. Keratin-based products have
      recently shown stimulatory effects on wound repair. This study was to test the
      cellular response to wool-derived oxidized keratin in wound healing to further
      understand the biological mechanisms underlying observed clinical benefits of
      keratin-based products as wound treatments. In vitro scratch migration assays
      examined the effects of oxidized keratin on the migration of human skin
      keratinocytes. Western blotting analysis determined the effects on the marker
      protein expression of type IV and type VII collagens and keratin 17. We found
      wool-derived oxidized keratin promoted keratinocyte migration and induced protein
      expression of type IV and type VII collagens, but not keratin 17. The data
      suggest that the beneficial effects of keratin-based treatment in wounds may be
      related to its positive effects on re-epithelialization via stimulating
      keratinocyte migration and production of basement membrane proteins of types IV
      and VII collagens.

PMID- 22621189
TI  - CD158k/KIR3DL2 and NKp46 are frequently expressed in transformed mycosis
      fungoides.
AB  - Malignant Sezary cells express the natural killer (NK) receptors KIR3DL2 (CD158k)
      and Nkp46 and may co-express activating killer immunoglobulin-like receptors
      (KIR) that may participate to neoplastic T-cell activation through the JNK
      pathway. Little is known regarding NK receptor expression in other cutaneous T
      cell lymphomas. We studied the expression of KIR and natural cytotoxicity
      receptor (NCR) transcripts, and KIR3DL1/2 at the protein level, in 16 skin
      biopsies from 10 patients with transformed mycosis fungoides (tMF). Some KIR and
      NCR transcripts were found in all cases, with various repertoires. Two to nine
      different KIR receptors were expressed in a single biopsy. Among them, KIR3DL2
      was the most frequent, with the highest level of expression in quantitative
      analyses and correlated with in situ protein expression, while phosphorylated JNK
      was never detected. Among NCR, NKp46 was expressed in all investigated cases. The
      role of KIR3DL2 and NKp46 in tMF oncogenesis remains to be studied.

PMID- 22621190
TI  - High genetic diversity of Staphylococcus aureus strains colonizing patients with
      epidermolysis bullosa.
AB  - Patients with the blistering disease, epidermolysis bullosa (EB), frequently
      suffer from chronic wounds that become colonized by pathogenic bacteria, such as
      Staphylococcus aureus. To determine S. aureus colonization rates in patients with
      EB, swabs were collected from the anterior nares, throats and wounds of 52 Dutch
      patients with EB. Swabs were also collected from nares and throats of 13
      healthcare workers who occasionally meet the sampled patients with EB. All EB
      patients with chronic wounds and 75% of the patients without chronic wounds were
      colonized with S. aureus. In contrast, 39% of the sampled healthcare workers were
      colonized with S. aureus. Typing revealed a high degree of genetic diversity of
      184 collected S. aureus isolates. Autoinoculation of S. aureus in individual
      patients with EB was shown to occur frequently, whereas transmission of S. aureus
      between patients with EB is apparently rare. There was no evidence for S. aureus
      transmission between patients with EB and healthcare workers.

PMID- 22621191
TI  - Myo/Nog cells in normal, wounded and tumor-bearing skin.
AB  - Murine and human skin were examined for the presence of Myo/Nog cells that were
      originally discovered in the chick embryo by their expression of MyoD mRNA,
      noggin and the G8 antigen. Myo/Nog cells are the primary source of noggin in
      telogen hair follicles. They are scarce within the interfollicular dermis and
      absent in the epidermis. Within 24 h following epidermal abrasion, Myo/Nog cells
      increase in number in the follicles and appear in the wound. Myo/Nog cells are
      also recruited to the stroma of tumors formed from v-Ras-transformed
      keratinocytes (Ker/Ras). Human squamous cell carcinomas and malignant melanomas
      contain significantly more Myo/Nog cells than basal cell carcinomas. Myo/Nog
      cells are distinct from macrophages, granulocytes and cells expressing alpha
      smooth muscle actin in the tumor stroma. Myo/Nog cells may be modulators of skin
      homoeostasis and wound healing, and potential diagnostic and therapeutic targets
      in skin cancer.

PMID- 22621192
TI  - Identification of an Alu-mediated 12.2-kb deletion of the complete LPAR6 (P2RY5)
      gene in a Turkish family with hypotrichosis and woolly hair.
AB  - Hypotrichosis is a rare form of progressive hair loss characterized by sparse and
      occasionally woolly hair that is curly and breaks easily. Disease-causing
      mutations in LIPH, LPAR6 and KRT74 have recently been identified. We describe a
      four-generation pedigree from Turkey following an autosomal recessive pattern, in
      which the four affected members had hypotrichosis and woolly hair. By sequencing
      LPAR6 and the use of SNP arrays, we revealed a homozygous loss of the entire
      LPAR6 gene in the affected individuals. We hypothesize that the 12-kb deletion
      resulted from illegitimate recombination secondary to slip-replication. The
      orientation of three Alu repeats around LPAR6 may have provoked the formation of
      a 'triple-barrel' structure during replication, thereby allowing strand slipping.
      This first report of complete LPAR6 loss expands the spectrum of known LPAR6
      mutations and suggests a novel mechanism for this gene and for the formation of
      DNA rearrangements in general.

PMID- 22621193
TI  - Dioxinodehydroeckol inhibits melanin synthesis through PI3K/Akt signalling
      pathway in alpha-melanocyte-stimulating hormone-treated B16F10 cells.
AB  - Antimelanogenic activity has previously been reported in ethyl acetate fraction
      of Ecklonia stolonifera. In this study, using the isolated dioxinodehydroeckol
      from the fraction, we sought to investigate an antimelanogenic signalling pathway
      in alpha-melanocyte-stimulating hormone (alpha-MSH)-stimulated B16F10 melanoma
      cells. Treatment with dioxinodehydroeckol inhibited the cellular melanin contents
      and expression of melanogenesis-related proteins, including microphthalmia
      associated transcription factor (MITF), tyrosinase and tyrosinase-related
      proteins TRP-1 and TRP-2. Moreover, dioxinodehydroeckol stimulated
      phosphorylation of Akt in a dose-dependent manner without affecting
      phosphorylation of ERK. These data suggest that dioxinodehydroeckol reduces
      melanin synthesis through the MITF regulation dependent upon PI3K/Akt signalling
      pathway.

PMID- 22621194
TI  - DNA-triggered AIM2 inflammasome activation in keratinocytes: Comment on Kopfnagel
      et al. Exp Dermatol. 2011. 20:1027-9.

PMID- 22621196
TI  - Alopecia areata as a model for T cell-dependent autoimmune diseases.

PMID- 22621197
TI  - Tapping natural variation at functional level reveals allele specific molecular
      characteristics of potato invertase Pain-1.
AB  - Biochemical, molecular and genetic studies emphasize the role of the potato
      vacuolar invertase Pain-1 in the accumulation of reducing sugars in potato tubers
      upon cold storage, and thereby its influence on the quality of potato chips and
      French fries. Previous studies showed that natural Pain-1 cDNA alleles were
      associated with better chip quality and higher tuber starch content. In this
      study, we focused on the functional characterization of these alleles. A genotype
      dependent transient increase of total Pain-1 transcript levels in cold-stored
      tubers of six different genotypes as well as allele-specific expression patterns
      were detected. 3D modelling revealed putative structural differences between
      allelic Pain-1 proteins at the molecule's surface and at the substrate binding
      site. Furthermore, the yeast SUC2 mutant was complemented with Pain-1 cDNA
      alleles and enzymatic parameters of the heterologous expressed proteins were
      measured at 30 and 4  degrees C. Significant differences between the alleles were
      detected. The observed functional differences between Pain-1 alleles did not
      permit final conclusions on the mechanism of their association with tuber quality
      traits. Our results show that natural allelic variation at the functional level
      is present in potato, and that the heterozygous genetic background influences the
      manifestation of this variation.

PMID- 22621198
TI  - M-M bond-stretching energy landscapes for M2(dimen)4(2+) (M = Rh, Ir; dimen = 1,8
      diisocyanomenthane) complexes.
AB  - Isomers of Ir(2)(dimen)(4)(2+) (dimen = 1,8-diisocyanomenthane) exhibit different
      Ir-Ir bond distances in a 2:1 MTHF/EtCN solution (MTHF = 2
      methyltetrahydrofuran). Variable-temperature absorption data suggest that the
      isomer with the shorter Ir-Ir distance is favored at room temperature [K = ~8;
      DeltaH degrees  = -0.8 kcal/mol; DeltaS degrees  = 1.44 cal mol(-1) K(-1)]. We
      report calculations that shed light on M(2)(dimen)(4)(2+) (M = Rh, Ir) structural
      differences: (1) metal-metal interaction favors short distances; (2) ligand
      deformational-strain energy favors long distances; (3) out-of-plane (A(2u))
      distortion promotes twisting of the ligand backbone at short metal-metal
      separations. Calculated potential-energy surfaces reveal a double minimum for
      Ir(2)(dimen)(4)(2+) (~4.1 A Ir-Ir with 0 degrees  twist angle and ~3.6 A Ir-Ir
      with +/-12 degrees  twist angle) but not for the rhodium analogue (~4.5 A Rh-Rh
      with no twisting). Because both the ligand strain and A(2u) distortional energy
      are virtually identical for the two complexes, the strength of the metal-metal
      interaction is the determining factor. On the basis of the magnitude of this
      interaction, we obtain the following results: (1) a single-minimum (along the Ir
      Ir coordinate), harmonic potential-energy surface for the triplet electronic
      excited state of Ir(2)(dimen)(4)(2+) (R(e,Ir-Ir) = 2.87 A; F(Ir-Ir) = 0.99 mdyn
      A(-1)); (2) a single-minimum, anharmonic surface for the ground state of
      Rh(2)(dimen)(4)(2+) (R(e,Rh-Rh) = 3.23 A; F(Rh-Rh) = 0.09 mdyn A(-1)); (3) a
      double-minimum (along the Ir-Ir coordinate) surface for the ground state of
      Ir(2)(dimen)(4)(2+) (R(e,Ir-Ir) = 3.23 A; F(Ir-Ir) = 0.16 mdyn A(-1)).

PMID- 22621199
TI  - C-H activation of terminal alkynes by tris-(3,5
      dimethylpyrazolyl)boraterhodiumneopentylisocyanide: new metal-carbon bond
      strengths.
AB  - C-H bond activation of terminal alkynes by [Tp'Rh(CNneopentyl)] (Tp' =
      hydridotris-(3,5-dimethylpyrazolyl)borate) resulted in the formation of terminal
      C-H bond activation products Tp'Rh(CNneopentyl)(C=CR)H (R = t-Bu, SiMe(3), hexyl,
      CF(3), p-MeOC(6)H(4), Ph, and p-CF(3)C(6)H(4)). A combination of kinetic
      selectivity determined in competition reactions and activation energy for
      reductive elimination has allowed for the calculation of relative Rh-C(alkynyl)
      bond strengths. The bond strengths of Rh-C(alkynyl) products are noticeably
      higher than those of Rh-C(aryl) and Rh-C(alkyl) analogues. The relationship
      between M-C and C-H bond strengths showed a linear correlation (slope R(M-C/H-C)
      = 1.32), and follows energy correlations previously established for unsubstituted
      sp(2) and sp(3) C-H bonds in aliphatic and aromatic hydrocarbons.

PMID- 22621200
TI  - Free surface electrospinning of fibers containing microparticles.
AB  - Many materials have been fabricated using electrospinning, including
      pharmaceutical formulations, superhydrophobic surfaces, catalysis supports,
      filters, and tissue engineering scaffolds. Often these materials can benefit from
      microparticles included within the electrospun fibers. In this work, we evaluate
      a high-throughput free surface electrospinning technique to prepare fibers
      containing microparticles. We investigate the spinnability of
      polyvinylpyrrolidone (PVP) solutions containing suspended polystyrene (PS) beads
      of 1, 3, 5, and 10 MUm diameter in order to better understand free surface
      electrospinning of particle suspensions. PS bead suspensions with both 55 kDa PVP
      and 1.3 MDa PVP were spinnable at 1:10, 1:5, and 1:2 PS:PVP mass loadings for all
      particle sizes studied. The final average fiber diameters ranged from 0.47 to 1.2
      MUm and were independent of the particle size and particle loading, indicating
      that the fiber diameter can be smaller than the particles entrained and can
      furthermore be adjusted based on solution properties and electrospinning
      parameters, as is the case for electrospinning of solutions without particles.

PMID- 22621201
TI  - Prescribing and partnership with patients.
AB  - There have been widespread changes in society and the roles of professionals.
      This change is also reflected in health care, where there is now acceptance of
      the need to involve patients in decision making. In prescribing specifically, the
      concordance agenda was developed alongside these initiatives to encourage
      improved medication taking and reduce wastage. However the extent to which these
      partnerships are delivered in practice remains unclear. This paper explores some
      of the issues to be considered when preparing patients and professionals for
      partnership and summarizes the limited evidence of barriers to, and benefits of,
      this approach. Firstly patients must be given the confidence, skills and
      knowledge to be partners. They need information about medicines, provided in ways
      known to be acceptable to them. Likewise professionals may need new skills to be
      partners. They need to understand the patient agenda and may need training and
      support to change the ways in which they consult with patients. There are also
      practical issues such as the perceived increase in time taken when consulting in
      partnership mode, room layout, computer interfaces and record keeping. Health
      care professionals other than doctors are also expected to behave in partnership
      mode, whether this is as prescribers in their own right or in supporting the
      prescribing of others. Whilst much has been claimed for the benefit of
      partnership approaches, hard evidence is limited. However whilst there is still
      much more to understand there will be no going back to the paternalistic model of
      the mid 20th century.

PMID- 22621202
TI  - Influence of the membrane lipophilic environment on the structure and on the
      substrate access/egress routes of the human aromatase enzyme. A computational
      study.
AB  - Human aromatase (HA), an enzyme located on the membrane of the endoplasmatic
      reticulum, is of crucial biological importance in the biosynthesis of estrogens.
      High levels of estrogens are related with important pathologies, conferring to HA
      a key role as a pharmacological target. In this study we provide, for the first
      time, an atomistic model of HA embedded on a membrane model to understand the
      influence of the membrane lipophilic environment on the structural and dynamical
      properties of HA and on the access/egress pathways of the substrate
      (androstenedione, ASD) and of the oxygen molecule (involved in the enzymatic
      process) into/from the HA active site. To this end we used several computational
      techniques such as force field-based molecular dynamics (MD) simulations, Random
      Expulsion MD, Steered MD, and Implicit Ligand Sampling. Our results show that the
      membrane anchoring does not markedly affect the structural properties and the
      flexibility of the protein, but they clearly point out that the membrane has a
      marked effect on the access/egress routes of the reactants, stabilizing the
      formation of different channels for both ASD and O(2) with respect to those
      observed in pure water solution. Due to the importance of HA in medicine and
      since access/egress channels may influence its substrate selectivity, a detailed
      understanding of the role of the membrane in shaping these channels may be of
      valuable help in drug design.

PMID- 22621203
TI  - Facial soft tissue thickness database for craniofacial reconstruction in Korean
      adults.
AB  - One hundred Korean adults (50 men, 50 women) were scanned in the upright position
      using a cone-beam CT (CBCT) scanner. The soft tissue (ST) thicknesses were
      measured at 31 landmarks, 10 midline and 21 bilateral landmark sites, and the
      means and standard deviations were obtained for male and female subjects. While
      18 of 31 landmarks showed sex differences, the majority showed higher values for
      male subjects with the exception of a few landmark sites corresponding to the
      zygoma area, which showed smaller values in men than in women. The mandibular
      area showed greater differences between the right and left sides. Overall, the ST
      thickness measurements obtained in this study can be used as a database for the
      forensic craniofacial reconstruction of Korean adult faces.

PMID- 22621204
TI  - KO(t)Bu mediated synthesis of phenanthridinones and dibenzoazepinones.
AB  - Synthesis of substituted phenanthridinones and dibenzoazepinones has been
      realized from 2-halo-benzamides in the presence of potassium tert-butoxide and a
      catalytic amount of 1,10-phenanthroline or AIBN. This new carbon-carbon bond
      forming reaction gives direct access to various biaryl lactams containing six-
      and seven-membered rings chemoselectively. Carbon-carbon coupling seems to
      proceed by the generation of a radical in the amide ring which leads to C-H
      arylation of aniline.

PMID- 22621205
TI  - Disruption of rhythms of molecular clocks in primary synovial fibroblasts of
      patients with osteoarthritis and rheumatoid arthritis, role of IL-1beta/TNF.
AB  - INTRODUCTION: Circadian rhythms play an important role in the body and in single
      cells. Rhythms of molecular clocks have not been investigated in synovial
      fibroblasts (SF) of patients with osteoarthritis (OA) and rheumatoid arthritis
      (RA). The study was initiated to fill this gap and to study effects of
      interleukin (IL)-1beta/tumor necrosis factor (TNF) on rhythmicity in synovial
      fibroblasts of RA and OA patients. METHODS: The presence of BMAL-1, CLOCK, Period
      1 and Period 2 proteins in synovial tissue was investigated by
      immunofluorescence. The presence of mRNA of molecular clocks was studied during
      72 h by qPCR. Characteristics of rhythms were studied with time series analysis.
      RESULTS: BMAL-1, CLOCK, Period 1 and Period 2 proteins were abundantly present in
      synovial tissue of OA, RA and controls. Receiving synovial tissue at different
      operation time points during the day (8:00 am to 4:00 pm) did not reveal a rhythm
      of BMAL-1 or Period 1 protein. In OASF and RASF, no typical rhythm curve of
      molecular clock mRNA was observed. Time series analysis identified a first peak
      between 2 and 18 hours after synchronization but a period was not detectable due
      to loss of rhythm. TNF inhibited mRNA of CLOCK, Period 1 and Period 2 in OASF,
      while IL-1beta and TNF increased these factors in RASF. This was supported by
      dose-dependently increased levels in MH7A RA fibroblasts. In RASF, IL-1beta and
      TNF shifted the first peak of BMAL-1 mRNA to later time points (8 h to 14 h).
      CONCLUSION: Rhythmicity is not present in primary OASF and RASF, which is
      unexpected because fibroblasts usually demonstrate perfect rhythms during several
      days. This might lead to uncoupling of important cellular pathways.

PMID- 22621206
TI  - Dexamethasone-induced eosinopenia is associated with lower progesterone
      production in cattle.
AB  - Eosinophilic cells accumulate in the capillaries of the bovine Graafian follicle
      shortly before ovulation and in the early developing corpus luteum (CL).
      Suppressing the migration of these eosinophilic cells by dexamethasone allowed us
      to evaluate their possible function in the CL development. Brown Swiss cows (n =
      10) were randomly subdivided into two groups (n = 5). Every group was used once
      as control group and once as experimental group with two oestrous cycles between
      each treatment. Eighteen hours (h) after oestrus synchronization, dexamethasone
      or saline was given. Ovulation was induced 24 h later with gonadotropin-releasing
      hormone. Another injection of dexamethasone or saline was given 12 h later.
      Eosinophilic cells in the blood were counted daily until day 7 after the first
      dexamethasone injection. The collection of ovaries took place at days 1, 2 and 5.
      Gene expression, protein concentration and location of angiogenic factors,
      chemokines, insulin-like growth factor 1 (IGF1) and eosinophilic cells were
      studied. No eosinophilic cells were found in the CL of the treatment group. Blood
      progesterone decreased significantly in the dexamethasone group from day 8 to 17.
      The protein concentration of FGF2 increased significantly in CL tissue at day 2
      and VEGFA decreased. Local IGF1 gene expression in the CL was not regulated. We
      assume from our data that the migration of eosinophilic cells into the early CL
      is not an essential, but an important stimulus for angiogenesis during early CL
      development in cattle.

PMID- 22621207
TI  - Thyroid stimulating hormone, independent of thyroid hormone, can elevate the
      serum total cholesterol level in patients with coronary heart disease: a cross
      sectional design.
AB  - BACKGROUND: The relationship between TSH and the lipid profile is contradictory
      because few studies have excluded the potential influence of the thyroid hormones
      (TH). The aim of the present study was to evaluate the relationship between serum
      TSH levels and the lipid profile independent of TH. METHODS: 1302 CHD patients
      diagnosed by coronary angiography were retrospectively studied. The prevalence
      and distribution of thyroid dysfunction were analyzed first. To assess the impact
      of TSH on serum lipids, Pearson's correlation analysis was performed after
      adjustments for classic factors and TH. To calculate the extent of the effect of
      TSH on the serum cholesterol level, the partial least squares method and
      additional statistical methods were used. RESULTS: After the exclusions, a total
      of 568 patients (270 males and 298 females with a mean age of 63.56 +/- 11.376
      years) were selected. The prevalence of thyroid dysfunction among the patients
      was 18.66%, and the prevalence of hypothyroidism (15.32%) was higher than that of
      hyperthyroidism (3.34%). Even after adjusting for confounding factors, such as
      sex, age, smoking status, fasting plasma glucose levels and TH, a significant
      positive impact of TSH on the serum total cholesterol (TC) level was revealed (r
      = 0.095, p = 0.036). Each 1 mIU/L increase in the TSH level might be linked to a
      0.015580712 mmol/L elevation of the serum TC value. CONCLUSIONS: TSH can increase
      the TC level in CHD patients independent of TH. The present study suggests a
      potential physiological role of TSH and the importance of maintaining an
      appropriate TSH level in CHD patients.

PMID- 22621208
TI  - Nested PCR-positive tubercular ampiginous choroiditis: a case report.
AB  - OBJECTIVE: To report on ampiginous choroiditis of tubercular etiology with nPCR
      positivity for M. tb in aqueous sample and also to stress upon the usefulness of
      nPCR to consolidate the etiological diagnosis. MATERIAL AND METHODS: Case report
      of a patient presenting with active ampiginous choroiditis with no evidence of
      systemic TB but had hilar and para-tracheal lymphadenopathy on CT chest.
      QuantiFERON TB gold test was positive The patient responded inadequately to
      systemic anti-tubercular treatment and oral steroids. Nested PCR for M.tb was
      done on aqueous sample was positive for MPB64 gene of M.tb. Anti-TB treatment was
      continued inspite of initial poor response to which the patient responded and his
      choroiditis regressed. RESULTS: Ocular tuberculosis forms the essential
      differential diagnosis of any chronic or recurrent choroiditis, especially in
      high endemic areas. The presumed tubercular etiology can be substantiated using
      highly sensitive and specific tests such as nested PCR on intraocular fluid.

PMID- 22621209
TI  - Treatment of severe inflammatory eye disease in patients of reproductive age and
      during pregnancy.
AB  - Inflammatory eye diseases (IED) such as uveitis affect females and males in the
      prime of their reproductive life. Despite their propensity to lead to significant
      visual loss, there have been very few studies of the management of patients with
      IED who are pregnant or plan a pregnancy during the course of therapy. The first
      trimester and postpartum period may be associated with an exacerbation of IED and
      it is important to have available medications that control the disease and do not
      cause miscarriage or fetal abnormalities. Several immunosuppressive drugs are
      contraindicated in pregnancy (methotrexate and alkylating agents), while others
      (corticosteroids, azathioprine, and cyclosporin) may be considered for use in
      pregnancy. Most drugs are excluded from use in pregnancy not because of proven
      teratogenicity but because of the lack of available evidence of their safety for
      the fetus.

PMID- 22621210
TI  - Effect of prolonged oral acyclovir treatment in acute retinal necrosis.
AB  - BACKGROUND: To examine the effectiveness of prolonged oral acyclovir treatment in
      patients with acute retinal necrosis (ARN). METHODS: Fifty-five ARN patients (62
      eyes) who had been treated with short-term or long-term oral acyclovir were
      identified in this retrospective study: one group treated with prolonged oral
      acyclovir (>=14 weeks) and the other group treated with a shorter duration of
      oral acyclovir (<14 weeks). The authors examined whether the prolonged treatment
      reduced the involvement of the contralateral eye. They also evaluated prognostic
      factors for visual outcome. RESULTS: Prolonged oral acyclovir treatment reduced
      the involvement of the contralateral eye (p = .036). The visual outcome was
      influenced by the timing of treatment initiation after symptom onset (p = .030),
      the age of the patient (p = .027), the area of retinal disease (p = .026), and
      the retinal detachment (p = .002). CONCLUSIONS: Prolonged oral acyclovir
      treatment had a significant role in preventing the involvement of the
      contralateral eye.

PMID- 22621211
TI  - Autophagy-related gene 7 is downstream of heat shock protein 27 in the regulation
      of eye morphology, polyglutamine toxicity, and lifespan in Drosophila.
AB  - BACKGROUND: Autophagy and molecular chaperones both regulate protein homeostasis
      and maintain important physiological functions. Atg7 (autophagy-related gene 7)
      and Hsp27 (heat shock protein 27) are involved in the regulation of
      neurodegeneration and aging. However, the genetic connection between Atg7 and
      Hsp27 is not known. METHODS: The appearances of the fly eyes from the different
      genetic interactions with or without polyglutamine toxicity were examined by
      light microscopy and scanning electronic microscopy. Immunofluorescence was used
      to check the effect of Atg7 and Hsp27 knockdown on the formation of
      autophagosomes. The lifespan of altered expression of Hsp27 or Atg7 and that of
      the combination of the two different gene expression were measured. RESULTS: We
      used the Drosophila eye as a model system to examine the epistatic relationship
      between Hsp27 and Atg7. We found that both genes are involved in normal eye
      development, and that overexpression of Atg7 could eliminate the need for Hsp27
      but Hsp27 could not rescue Atg7 deficient phenotypes. Using a polyglutamine
      toxicity assay (41Q) to model neurodegeneration, we showed that both Atg7 and
      Hsp27 can suppress weak, toxic effect by 41Q, and that overexpression of Atg7
      improves the worsened mosaic eyes by the knockdown of Hsp27 under 41Q. We also
      showed that overexpression of Atg7 extends lifespan and the knockdown of Atg7 or
      Hsp27 by RNAi reduces lifespan. RNAi-knockdown of Atg7 expression can block the
      extended lifespan phenotype by Hsp27 overexpression, and overexpression of Atg7
      can extend lifespan even under Hsp27 knockdown by RNAi. CONCLUSIONS: We propose
      that Atg7 acts downstream of Hsp27 in the regulation of eye morphology,
      polyglutamine toxicity, and lifespan in Drosophila.

PMID- 22621213
TI  - Development of human hepatocellular carcinoma cell-targeted protein cages.
AB  - We described herein a human hepatocellular carcinoma (HCC) cell-targeted protein
      cage for which the HCC-binding peptide termed SP94 was modified at the surface of
      a naturally occurred heat shock protein (Hsp) cage. Six types of HCC-targeted Hsp
      cages were chemically synthesized using two types of heterobifunctional linker
      (SM(PEG)(n)) with different lengths and two types of SP94 peptide, which
      contained a unique Cys residue at the N- or C-terminus of the peptide. These Hsp
      cages were characterized using matrix-assisted laser desorption/ionization-time
      of-flight mass spectrometry (MALDI-ToF MS) analyses, sodium dodecylsulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) analyses, and dynamic light
      scattering (DLS) measurement. Fluorescence microscopic observations revealed that
      all the engineered protein cages bind selectively to HCC cells but not to the
      other cell lines tested (including normal liver cell). Moreover, the number of
      SP94 peptides on Hsp cages, conjugation site of SP94 peptide, and linker length
      between a Hsp cage and a SP94 peptide had important effects upon the binding of
      engineered Hsp cages to HCC cells. An engineered Hsp cage conjugated to the N
      terminus of SP94 peptide via a longer linker molecule and containing high SP94
      peptide levels showed greater binding toward HCC cells. Surprisingly, through
      optimization of these three factors, up to 10-fold greater affinity toward HCC
      cells was achieved. These results are critically important not only for the
      development of HCC cell-targeting devices using SP94 peptide, but also to create
      other cell-targeting materials that utilize other peptide ligands.

PMID- 22621212
TI  - Allogeneic and xenogeneic transplantation of adipose-derived stem cells in
      immunocompetent recipients without immunosuppressants.
AB  - Mesenchymal stem cells (MSCs) are well known for their immunomodulatory
      capabilities. In particular, their immunosuppressive property is believed to
      permit their allogeneic or even xenogeneic transplantation into immunocompetent
      recipients without the use of immunosuppressants. Adipose-derived stem cell
      (ADSC), owing to its ease of isolation from an abundant tissue source, is a
      promising MSC for the treatment of a wide range of diseases. ADSC has been shown
      to lack major histocompatibility complex-II expression, and its immunosuppressive
      effects mediated by prostaglandin E2. Both preclinical and clinical studies have
      shown that allogeneic transplantation of ADSCs was able to control graft-versus
      host disease. In regard to xenotransplantation a total of 27 preclinical studies
      have been published, with 20 of them performed with the investigators' intent.
      All 27 studies used ADSCs isolated from humans, possibly due to the wide
      availability of lipoaspirates. On the other hand, the recipients were mouse in 13
      studies, rat in 11, rabbit in 2, and dog in 1. The targeted diseases varied
      greatly but all showed significant improvements after ADSC xenotransplantation.
      For clinical application in human medicine, ADSC xenotransplantation offers no
      obvious advantage over autotransplantation. But in veterinary medicine,
      xenotransplantation with porcine ADSC is a practical alternative to the costly
      and inconvenient autotransplantation.

PMID- 22621214
TI  - Interleukin 1 gene cluster SNPs (rs1800587, rs1143634) influences post
      orthodontic root resorption in endodontic and their contralateral vital control
      teeth differently.
AB  - AIM: To investigate whether the genetic variants of the interleukin-1 gene
      cluster (IL1) are associated with a possible genetically induced variability in
      post-orthodontic external apical root resorption (EARR) in root filled teeth and
      their control counterparts with vital pulps. METHODOLOGY: One hundred and forty
      six maxillary premolars were evaluated radiographically following orthodontic
      treatment. Genetic screening was performed on orthodontic patients for two single
      nucleotide polymorphisms (SNPs: rs1800587 and rs1143634) in the IL1 gene cluster.
      Subjects were divided into two groups according to the presence or absence of
      radiographic post-orthodontic EARR (>2 mm) in root filled teeth and their
      controls with vital pulps. Logistic regression analysis was performed to obtain
      an adjusted estimation between EARR and IL1 polymorphisms. Allelic frequencies,
      genotype distributions, and adjusted odds ratio (OR), at 95% confidence interval,
      were also calculated. RESULTS: Whilst no clear statistical association was found
      for gene variations in IL1A, a sound association was found in the comparative
      analysis of subjects homozygous [2/2(TT)] for the IL1B gene, which resulted in a
      two times increased risk of suffering post-orthodontic EARR in root filled teeth
      [OR, 2.032 (P = 0.031); CI,1.99-14.77] when compared with their controls with
      vital pulps. There was, however, a shared predisposition to EARR in controls with
      vital pulps and root filled teeth of subjects homozygous for allele 1 [OR, 5.05
      (P = 0.002)] and [OR, 2.77 (P = 0.037)], respectively. CONCLUSIONS: Genetic
      variations in the interleukin-1beta gene (rs1143634) predispose root filled teeth
      to EARR for matched pairs secondary to orthodontic treatment in a different way
      from their control teeth with vital pulps in subjects homozygous for allele 2
      [2/2(TT)].

PMID- 22621216
TI  - The pharmacogenetics of beta-adrenergic receptor antagonists in the treatment of
      hypertension and heart failure.
AB  - INTRODUCTION: beta-Blockers have an important therapeutic role throughout the
      cardiovascular continuum. However, there is considerable variation in response to
      these drugs, which may be related to genetic influences on their pharmacokinetics
      and pharmacodynamic effects. AREAS COVERED: This review focuses on genetic
      variations in the drug metabolizing enzymes which influence the pharmacokinetics
      and potentially the pharmacodynamics of some beta-blockers. It also reviews the
      polymorphisms in the adrenergic receptors (ARs) and their related pathways which
      are likely to influence the responses to beta-blockers. EXPERT OPINION: The
      CYP2D6 genotypes influence the pharmacokinetics of some beta-blockers but the
      effects on beta-blocker responses have been inconsistent and there is currently
      no general role for CYP2D6 genotyping prior to choosing a particular beta-blocker
      or dose. The common polymorphisms producing changes in the beta(1)-ARs, and their
      signaling pathways, have been associated with clinical outcomes in several
      studies in hypertension and heart failure. Treatment with beta-blockers,
      especially with higher doses, appears to have greater benefits in patients with
      the genetic forms of the beta(1)-ARs which are more responsive to both agonists
      and antagonists. However, current data are not sufficiently consistent to support
      genotyping for these polymorphisms before selecting or initiating beta-blocker
      treatment and further study results are needed to clarify the situation.

PMID- 22621218
TI  - Evidence-based clinical practice guideline for renal cell carcinoma: the Japanese
      Urological Association 2011 update.
AB  - Remarkable advances have been made in medical practice in relation to renal cell
      carcinoma in recent years, and a large amount of new evidence has been
      accumulated. In keeping with the plan at the time the first version of the
      "Evidence-Based Clinical Practice Guideline for Renal Cell Carcinoma" compiled by
      the Japanese Urological Association was published in 2007, the Japanese
      Urological Association has just published a revised 2011 version. The main
      revisions regard the selection of treatment methods according to prognostic
      factors, reconsideration of treatment methods for small-diameter renal cell
      carcinoma and selection criteria for medical treatment of advanced renal cell
      carcinoma, including selection of neoadjuvant treatment with molecular targeted
      medicines. This Guideline presents clinical practice methods that are thought to
      be the most standard methods in Japan at the present time. In this English
      translation of a shortened version of the original Guideline, we cited
      particularly important clinical questions and references.

PMID- 22621219
TI  - Editorial comment to involvement of estrogen receptors in prostatic diseases.

PMID- 22621220
TI  - Treatment of venous infraorbital dark circles using a long-pulsed 1,064-nm
      neodymium-doped yttrium aluminum garnet laser.
AB  - BACKGROUND: Infraorbital dark circles are a common cosmetic problem with multiple
      causative factors and few studies into the different treatment options.
      OBJECTIVE: To assess the effectiveness and safety of long-pulsed 1,064-nm
      neodymium-doped yttrium aluminum garnet (Nd:YAG) laser therapy for infraorbital
      dark circles caused by visible prominent veins. PARTICIPANTS AND METHODS: Twenty
      six patients with venous infraorbital dark circles were treated with a Nd:YAG
      laser (fluence, 130-140 J/cm(2) ; spot size, 6 mm) in double-pulse mode (pulse
      width, 6-10 ms; interpulse interval, 20 ms). Patients were examined 12 months
      after the final treatment. Results were ranked in five categories based on
      percentage clearance (5 = 100%, 4 = 75-99%, 3 = 50-74%, 2 = 25-49%, 1 <= 25%
      clearance). Patient satisfaction was ranked on a scale of 1 to 3 (1 = minimal
      improvement; 3 = completely satisfied), and pain was ranked on a scale of 1 to 10
      (1 = mild pain; 10 = severe pain). RESULTS: Twenty-six patients completed the
      study. Objective improvement scores were 5 in all patients, and all patient
      satisfaction scores were 3. All patients tolerated the moderate pain (mean score
      3.6). Transient erythema was observed in all patients. CONCLUSION: Long-pulsed
      1,064-nm Nd:YAG-laser treatment appears effective and safe for the treatment of
      venous infraorbital dark circles and selectively removes visible prominent veins.

PMID- 22621221
TI  - Effects of hydration during strontium exchange into nanoporous hydrogen niobium
      titanium silicate.
AB  - A Nb-substituted titanium silicate with the sitinakite (NbTS) topology was
      exchanged with Sr(2+) to determine the mechanisms and pathways of ion diffusion
      through this mixed polyhedral nanoporous framework. The refined structural models
      yield unit cell parameters and atomic positions of Sr(2+) and suggest that there
      was a two-step process during cation diffusion. The starting material of the
      exchange experiment was the H(+)-exchanged material,
      H(1.4)Nb(0.6)Ti(1.4)SiO(7).1.9H(2)O, with space group P4(2)/mcm. In the beginning
      of the exchange process, Sr filled the 8-membered-ring channel near the 4(2) axis
      in the center. Once the Sr(2+) fractional occupancy reached approximate 0.11, Sr
      positions and extra-framework H(2)O molecules shifted away from the central 8
      membered-ring toward the framework, and an increase in Sr hydration and framework
      bonding was observed. The new H(2)O positions resulted in a lowering of symmetry
      to the P 42m space group, and it is thought that the Sr migration served to
      enhance Sr(2+) ion diffusion capacity into the channels of NbTS since the
      exchange rate briefly accelerated after the 0.11 fractional occupancy level was
      passed. Exchange of Sr(2+) into the nanoporous material reached maximum
      fractional site occupancy of approximately 0.20 using a 10.0 mM SrCl(2) solution.

PMID- 22621222
TI  - Distinctive histopathological features that support a diagnosis of cholesterol
      ester storage disease in liver biopsy specimens.
AB  - AIMS:   To identify reliable criteria with which to improve the diagnosis of
      lysosomal acid lipase (LAL) deficiency of the cholesterol ester storage disease
      (CESD) type in liver biopsies. METHODS AND RESULTS:   We analysed a series of 16
      liver biopsies of LAL deficiency of the CESD type confirmed by enzyme testing and
      DNA sequencing. The biopsy appearances were compared with those of biopsies of
      other causes of fatty liver. A predominantly microvesicular steatosis in CESD
      patients could not be reliably distinguished from other causes of fatty liver
      with cytosolic lipid accumulation in fixed paraffin-embedded tissues routinely
      stained with haematoxylin and eosin. The presence of luminal (cathepsin D) and
      membrane lysosomal markers [lysosomal-associated membrane protein (LAMP)1, LAMP2,
      and lysosomal integral membrane protein 2] around the lipid vacuoles facilitated
      the diagnosis of CESD in fixed paraffin-embedded material. Additional diagnostic
      clues included autofluorescent detection of ceroid induction in storage
      macrophages and the absence of lipopigment in hepatocytes. Stored liquid crystals
      of cholesteryl esters, which are associated with Maltese cross-type
      birefringence, were best appreciated in unfixed biopsy samples. CONCLUSIONS:  
      The pathological diagnosis of CESD requires a high index of suspicion, and can be
      rapidly and effectively appreciated at the light microscopy level, even in
      routine fixed paraffin-embedded liver samples with immuohistochemical staining
      for lysosomal markers.

PMID- 22621224
TI  - Breastfeeding practices in New York State maternity hospitals: results from a
      statewide survey.
AB  - OBJECTIVE: This study characterized maternity hospital breastfeeding practices in
      New York. METHODS: The New York State Department of Health Breastfeeding Survey
      was sent to 138 hospitals providing maternity services to assess breastfeeding
      and rooming-in policies, infant feeding practices, breastfeeding training, staff
      structure, and support mechanisms. Additionally, hospital-specific exclusive
      breastfeeding rates were obtained from Hospital Profile data. RESULTS: The
      response rate was 100%. Ninety-three percent of the hospitals allowed 24-hour
      rooming-in, in all postpartum rooms. Eighty-six percent of hospitals employed a
      designated lactation coordinator. Less than 1.5% of hospitals routinely gave
      formula, pacifiers, or glucose water to a breastfed infant. These supplements are
      most commonly provided because of the mother's request. The largest reported
      barrier to initiating breastfeeding in the hospital was presenting mothers with
      mixed messages, whereas the largest patient barrier was identified as the
      mother's culture. All hospitals provided obstetric nursing staff with lactation
      education, whereas 46.4% trained physicians. Among healthy births, exclusive
      breastfeeding was statistically more likely to occur in hospitals offering only
      basic care (Level I) or subspecialty care (Level III), relative to Regional
      Perinatal Centers delivering the highest level of care, and was more likely with
      hospitals outside of New York City, relative to those within the city. After
      controlling for hospital location and level of care, exclusive breastfeeding was
      statistically more likely in hospitals that initiate breastfeeding immediately
      following an uncomplicated vaginal or cesarean birth. CONCLUSIONS: Mothers should
      be encouraged to initiate breastfeeding immediately after birth. Practices of
      Level I hospitals that lead to increased breastfeeding should be identified.

PMID- 22621223
TI  - Perceptions of primary care-based breastfeeding promotion interventions:
      qualitative analysis of randomized controlled trial participant interviews.
AB  - OBJECTIVE: This study examined women's perceptions and reported effects of
      routine, primary care-based interventions to increase breastfeeding. SUBJECTS AND
      METHODS: A subsample (n=67) of participants in randomized controlled trials
      (RCTs) completed semistructured exit interviews at 6 months postpartum. RCT arms
      included the following: (a) routine pre-/postnatal lactation consultant (LC)
      support (LC group); (b) electronic prompts (EP) guiding providers to discuss
      breastfeeding during prenatal care visits (EP group); (c) a combined intervention
      (LC+EP group); and (d) controls. Interview transcripts were coded and analyzed in
      MAX.qda. RESULTS: Key findings included the following: (1) Brief, non-directive
      assessment of feeding via postpartum interviews focused attention upon feeding
      practices. When coupled with breastfeeding promotion interventions, interviews
      promoted breastfeeding. (2) The EP and LC interventions were complementary: EPs
      influenced initiation, while LCs helped overcome barriers and sustain
      breastfeeding. (3) Prenatal intent to feed both breastmilk and formula was
      associated with the greatest receptivity to study messages. CONCLUSIONS: Findings
      underscore the need for interventions across the continuum of care. Trained LCs
      in prenatal/postpartum settings and prenatal care providers play important
      complementary roles that, when coupled with brief telephone feeding assessments,
      may improve breastfeeding rates.

PMID- 22621225
TI  - alpha-Sulfur crystals as a visible-light-active photocatalyst.
AB  - We show that in contrast to conventional compound photocatalysts, alpha-sulfur
      crystals of cyclooctasulfur (S(8)) are a visible-light-active elemental
      photocatalyst. The alpha-S crystals were found to have the ability not only to
      generate .OH radicals but also to split water in a photoelectrochemical process
      under both UV-vis and visible-light irradiation. Although the absolute activity
      obtained was low because of the large particle size and poor hydrophilicity of
      the alpha-S crystals studied, there is great potential for increasing the
      activity with the assistance of known strategies such as surface modification,
      nanoscaling, doping, and coupling with other photocatalysts.

PMID- 22621226
TI  - Facile synthesis of thermally stable poly(N-vinylpyrrolidone)-modified gold
      surfaces by surface-initiated atom transfer radical polymerization.
AB  - Well-controlled polymerization of N-vinylpyrrolidone (NVP) on Au surfaces by
      surface-initiated atom transfer radical polymerization (SI-ATRP) was carried out
      at room temperature by a silanization method. Initial attempts to graft poly(N
      vinylpyrrolidone) (PVP) layers from initiators attached to alkanethiol monolayers
      yielded PVP films with thicknesses less than 5 nm. The combined factors of the
      difficulty in the controllable polymerization of NVP and the instability of
      alkanethiol monolayers led to the difficulty in the controlled polymerization of
      NVP on Au surfaces. Therefore, the silanization method was employed to form an
      adhesion layer for initiator attachment. This method allowed well-defined ATRP
      polymerization to occur on Au surfaces. Water contact angle, X-ray photoelectron
      spectroscopy (XPS), and reflectance Fourier transform infrared (reflectance FTIR)
      spectroscopy were used to characterize the modified surfaces. The PVP-modified
      gold surface remained stable at 130  degrees C for 3 h, showing excellent thermal
      stability. Thus, postfunctionalization of polymer brushes at elevated
      temperatures is made possible. The silanization method was also applied to modify
      SPR chips and showed potential applications in biosensors and biochips.

PMID- 22621228
TI  - Cerebral hypoperfusion during carotid artery stenosis can lead to cognitive
      deficits that may be independent of white matter lesion load.
AB  - Studies investigating cognitive impairment in stroke-free patients with carotid
      artery stenosis have led to inconsistent results. Furthermore, the
      pathophysiological mechanism leading to cognitive impairment remains unclear.
      Cerebral hypoperfusion and arterio-arterial microembolization are discussed. The
      aims of our study were (1) to delineate patterns of cognitive impairment in
      stroke-free patients with carotid artery stenosis and (2) to investigate if
      cognitive impairment is independent of white matter lesion load in brain MRI. We
      identified 212 (93 women, mean age 70.2) stroke free, non-demented patients, who
      were referred for carotid artery stenting or because of subjective cognitive
      impairment. All patients completed a neurocognitive test battery measuring verbal
      fluency, constructional praxis, figural memory, verbal short-term- and long-term
      memory, verbal recognition memory, semantic processing, speed of cognitive
      processing and divided attention. Grade of maximum carotid artery stenosis was
      categorized into three groups (mild, moderate, or severe). White matter lesion
      load was graded using a visual rating scale. Cognitive test scores of groups with
      different grades of carotid artery stenosis were compared. Univariate regression
      analysis was used to measure the predictive value of carotid artery stenosis.
      Multivariate logistic regression analysis was performed when integrating carotid
      artery stenosis and white matter lesion load. Carotid artery stenosis negatively
      correlated with measures of verbal fluency, constructional praxis, verbal short
      term-memory, semantic processing, speed of cognitive processing, and divided
      attention. After adjustment for white matter lesions, carotid artery stenosis did
      not independently predict divided attention. Significance persisted in all other
      cognitive domains. In our selected group of patients, a higher grade of carotid
      artery stenosis is associated with cognitive decline. This process is independent
      of white matter lesion load. Possible pathophysiological implications are
      discussed.

PMID- 22621227
TI  - Short-term high-dose effect of lovastatin on thrombolysis by rt-PA in a human
      whole-blood in vitro clot model.
AB  - High-dose hydroxymethylglutaryl coenzyme. A reductase inhibitor (statin)
      administration reduces neuronal injury and improves outcomes in experimental
      models of acute ischemic stroke, and has been shown to be safe in a phase 1 dose
      escalation study using lovastatin at doses higher than currently approved for
      daily use. Statins also affect the hemostatic system by upregulating t-PA
      expression and decreasing plasminogen activator inhibitor (PAI-1) expression,
      platelet adhesion and thrombus formation in animal models. Since a thrombolytic
      agent, recombinant tissue plasminogen activator (rt-PA), is currently the only
      FDA-approved therapy for use in ischemic stroke patients, it is important to
      ascertain whether high statin doses impact the efficacy of rt-PA. The main goal
      of this study was to evaluate the effect of a high dose of lovastatin and its
      active form, lovastatin hydroxy acid, on rt-PA thrombolysis in an in vitro model.
      Percentage clot lysis was measured in the presence and absence of rt-PA in three
      different treatment groups: lovastatin, lovastatin hydroxy acid, and ethanol. The
      effect of ethanol on clot lysis was studied since ethanol was used to disperse
      the highly hydrophobic lovastatin. The decrease in clot width over time was
      measured using microscopic imaging of an in vitro human whole blood clot model;
      an approximately 400 MUm diameter clot was formed on suture silk, suspended in
      human fresh frozen plasma (hFFP) and exposed to treatment. In the absence of rt
      PA, clot lysis did not show statistically significant differences in the
      percentage clot lysis between different treatment groups (p=0.103). In the
      presence of rt-PA, clot lysis was greater than in the absence of rt-PA for all
      groups, but there were no statistically significant differences between treatment
      groups (p=0.385). In this in vitro study, high doses of lovastatin neither
      impaired nor enhanced the lytic efficacy of rt-PA.

PMID- 22621229
TI  - Decreased cerebral perfusion and oxidative stress result in acute and delayed
      cognitive impairment.
AB  - Chronic cerebral hypoperfusion (CCH) is common in the pathogenesis of cognitive
      impairment, in which oxidative stress plays an important role. Here we describe
      an alternative rat model for CCH that involves two-stage, three-vessel occlusion
      (2s-3VO) and compare its effects with those of permanent bilateral occlusion
      (2VO) of the common carotid arteries. Real-time cerebral blood flow (CBF) during
      the surgery was monitored. Spatial learning and memory were tested with the
      Morris water maze, and oxidative damage was evaluated by measuring
      malondialdehyde (MDA) levels in both the hippocampus and cortex. We found that
      the CBF drop in the early stage of the 2s-3VO model was more modest than that in
      the 2VO model. Like 2VO rats, 2s-3VO rats showed impaired spatial learning and
      memory and increased MDA levels 8 weeks after surgery. Interestingly, when
      pooling observations from previous studies, we confirmed that oxidative damage
      appeared later than spatial learning and memory deficits but lasted longer than
      did cerebral hypoperfusion. Thus, the 2s-3VO model appears to be a suitable model
      for the study of CCH. Moreover, data support the notion that cognitive impairment
      in CCH rat models may be induced early by cerebral hypoperfusion early and in a
      later phase by oxidative stress.

PMID- 22621230
TI  - Platelet microparticles induce angiogenesis and neurogenesis after cerebral
      ischemia.
AB  - Activated platelets shed microparticles, which contain a variety of growth
      factors central to angiogenesis and neurogenesis. The aim of this study was to
      explore whether platelet derived microparticles (PMP) can boost endogenous neural
      stem cells dependent repair mechanisms following stroke in a rat model. To
      examine the effects of PMP therapy in-vivo, we delivered PMP or vehicle via a
      biodegradable polymer to the brain surface after permanent middle cerebral artery
      occlusion (PMCAO) in rats. Rats were tested with the neurological severity score
      and infarct volumes were measured at 90 days post-ischemia. Immunohistochemistry
      was used to determine the fate of newborn cells and to count blood vessels in the
      ischemic brain. The results show that PMP led to a dose dependent increase in
      cell proliferation, neurogenesis and angiogenesis at the infarct boundary zone
      and significantly improved behavioral deficits.

PMID- 22621231
TI  - Polymorphisms at the LDLR locus may be associated with ischemic cerebrovascular
      disease independent of lipid profile.
AB  - The low-density lipoprotein receptor (LDLR) gene has been reported to be
      associated with cerebral infarction. This study aimed to explore 2 genetic LDLR
      variants, rs688 and rs5925, for their potential roles in cerebral infarction.
      This genetic association study was conducted within an isolated Taiwanese
      population; 815 ischemic stroke patients (431 with atherothrombotic stroke and
      384 with lacunar infarction) and 430 normal controls were enrolled. There was no
      significant difference in the genetic frequency of rs688 and rs5925 between the
      control group and overall ischemic stroke, atherothrombotic stroke, or lacunar
      infarct groups. However, when analyzing the association between the haplotypes
      related to rs688 and rs5925 and cerebral ischemic stroke, the most common
      haplotype allele CT was used as the reference allele, and the haplotype TC
      associated with a 65% increased risk of overall ischemic stroke, 72% increased
      risk of atherothrombotic stroke, and 70% increased risk of lacunar infarction;
      this indicated a synergistic effect between these 2 single-nucleotide
      polymorphisms. The LDLR analysis based on the haplotypes rs688 and rs5925 was
      conducted in a Taiwanese population and provided preliminary evidence suggesting
      that genetic polymorphisms of LDLR are associated with cerebral infarction.

PMID- 22621232
TI  - Enriched environment prevents cognitive impairment and tau hyperphosphorylation
      after chronic cerebral hypoperfusion.
AB  - Chronic cerebral hypoperfusion (CCH) has been gradually prevalent in the patients
      over middle age, especially the old over 60 years. It has been proved that CCH is
      highly related with cognitive impairment. CCH emerges not only in vascular
      dementia (VaD), but also in Alzheimer's disease (AD), which regarded as a
      critical causative for cognitive impairment in these diseases. Nevertheless, the
      mechanisms underlying cognitive deficit remain elusive. Moreover, there are no
      dramatically effective preventions. In the present study, by employing a
      recognized CCH rat model, we found that CCH induced spatial learning/memory
      deficits with simultaneously increasing tau hyperphosphorylation at multiple
      Alzheimer-related phosphorylation sites with activation of glycogen synthase
      kinase-3beta (GSK-3beta), Cyclin-dependent kinase (Cdk5), Calcium/calmodulin
      dependent protein kinase II (CaMKII), and protein kinase B (Akt), and inhibition
      of protein phosphatase (PP) 2A (PP-2A). Interestingly, enriched environment (EE)
      treatment, an effect environment stimuli filled with various novel objects, could
      prevent rats from the EE-induced memory deficits and alterations of tau
      hyperphosphorylation. Our data suggested that EE might be potentially used for
      attenuating the detrimental cognition induced by CCH through regulating tau
      hyperphosphorylation.

PMID- 22621233
TI  - DL-3-n-Butylphthalide, an anti-oxidant agent, prevents neurological deficits and
      cerebral injury following stroke per functional analysis, magnetic resonance
      imaging and histological assessment.
AB  - DL-3-n-Butylphthalide (NBP) is a synthetic compound based on L-3-n-Butylphthalide
      which was isolated from seeds of Apium graveolens. The present study aims at
      evaluating the outcome of NBP given prior to and after the onset of ischemic
      stroke in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto
      rats (WKY). Stroke was induced by the middle cerebral artery occlusion (MCAO) in
      SHR and WKY. For pre-treatment, NBP was administered to SHR and WKY daily for two
      months prior to MCAO. For post-treatment, NBP was given daily for seven
      consecutive days after MCAO. Seven days post-surgery, rats were tested for the
      presence of neurological deficits. Magnetic resonance imaging (MRI) and 2,3,5
      triphenyltetrazolium chloride (TTC) staining were employed to calculate the
      infarct volume. The cerebral cortex and corpus striatum in the ischemic penumbra
      area were examined microscopically for pathological changes. In SHR, NBP pre- and
      post-treatment significantly lowered neurological deficit scores, reduced infarct
      volume, and minimized pathological changes in the penumbra area when compared to
      oil-vehicle treated controls. In WKY, these beneficial effects were observed only
      in the post-treatment group. The beneficial effects of NBP post-treatment were
      greater in WKY than in SHR. Results indicated that NBP could exert both
      preventive and therapeutic effects on ischemic stroke in SHR, but only exerted
      therapeutic effect in WKY.

PMID- 22621234
TI  - Interleukin-1beta increases release of endothelin-1 and tumor necrosis factor as
      well as reactive oxygen species by peripheral leukocytes during experimental
      subarachnoid hemorrhage.
AB  - In the subarachnoid hemorrhage (SAH) blood mixes with cerebrospinal fluid, what
      starts immunoinflammatory processes - increased synthesis of proinflammatory
      cytokines, and formation of reactive oxygen species (ROS), resulting in pre
      activation of different populations of peripheral leukocytes. Migration of
      leukocytes to the brain parenchyma through broken blood brain barrier may produce
      extra brain tissue injury besides of that resulting from SAH. We examined in
      adult rats the effect of interleukin-1beta (IL-1beta) neutralization on secretion
      of cytokines as well as production of ROS in the course of SAH. SAH was produced
      by injection of 150 MUL of autologous arterial blood into cisterna magna. In 50%
      of animals, IL-1beta activity was inhibited by intracerebroventricular
      administration of anti-rat IL-1beta antibodies. Ninety minutes or 24 hrs
      following surgery, blood samples were drawn from the extraorbital plexus and
      centrifuged to obtain two leukocyte subpopulations - polymorphonuclear (PMN) and
      mononuclear (MN). The chemiluminescence, a hallmark of ROS synthesis, was
      measured in PMNs. In supernatants from MNs cultures, concentrations endothelin-1
      (ET-1), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were
      assessed. SAH caused the increase ofn PMNs chemiluminescence as well as the
      increase of production of ET-1 and TNF-alpha by MNs but had no influence on IL-6
      concentration. Neutralization of IL-1beta resulted in significant decrease of
      chemiluminescence as well as concentration of both ET-1 and TNF-alpha, while IL-6
      concentration was increased. These revealed an important role of IL-1beta in the
      activation of peripheral leukocytes in the course of subarachnoid hemorrhage.

PMID- 22621235
TI  - Efficient synthesis of alpha-tertiary alpha-silylamines from aryl
      sulfonylimidates via one-pot, sequential C-Si/C-C bond formations.
AB  - An efficient and flexible route for the synthesis of alpha-tertiary (alpha,alpha
      dibranched) alpha-silylamines via sequential reactions of sulfonylimidates using
      readily available phenyldimethylsilyllithium and Grignard reagents is described.
      The procedure allows successive formation of C-Si/C-C bonds in a single flask.

PMID- 22621236
TI  - Biomimetic cell culture proteins as extracellular matrices for stem cell
      differentiation.

PMID- 22621237
TI  - Learning sparse representations for fruit-fly gene expression pattern image
      annotation and retrieval.
AB  - BACKGROUND: Fruit fly embryogenesis is one of the best understood animal
      development systems, and the spatiotemporal gene expression dynamics in this
      process are captured by digital images. Analysis of these high-throughput images
      will provide novel insights into the functions, interactions, and networks of
      animal genes governing development. To facilitate comparative analysis, web-based
      interfaces have been developed to conduct image retrieval based on body part
      keywords and images. Currently, the keyword annotation of spatiotemporal gene
      expression patterns is conducted manually. However, this manual practice does not
      scale with the continuously expanding collection of images. In addition, existing
      image retrieval systems based on the expression patterns may be made more
      accurate using keywords. RESULTS: In this article, we adapt advanced data mining
      and computer vision techniques to address the key challenges in annotating and
      retrieving fruit fly gene expression pattern images. To boost the performance of
      image annotation and retrieval, we propose representations integrating spatial
      information and sparse features, overcoming the limitations of prior schemes.
      CONCLUSIONS: We perform systematic experimental studies to evaluate the proposed
      schemes in comparison with current methods. Experimental results indicate that
      the integration of spatial information and sparse features lead to consistent
      performance improvement in image annotation, while for the task of retrieval,
      sparse features alone yields better results.

PMID- 22621238
TI  - Evaluation of four affibody-based near-infrared fluorescent probes for optical
      imaging of epidermal growth factor receptor positive tumors.
AB  - The epidermal growth factor receptor 1 (EGFR) has become an attractive target for
      cancer molecular imaging and therapy. An Affibody protein with strong binding
      affinity for EGFR, ZEGFR:1907, has been reported. We are interested in
      translating Affibody molecules to potential clinical optical imaging of EGFR
      positive cancers. In this study, four anti-EGFR Affibody based near-infrared
      (NIR) fluorescent probes were thus prepared, and their in vivo performance was
      evaluated in the mice bearing EGFR positive subcutaneous A431 tumors. METHODS:
      The Affibody analogue, Ac-Cys-ZEGFR:1907, was synthesized using solid-phase
      peptide synthesis method. The purified small protein was then site-specifically
      conjugated with four NIR fluorescent dyes, Cy5.5-monomaleimide, Alex-Fluor-680
      maleimide, SRfluor680-maleimide, or IRDye-800CW-maleimide, to produce four
      optical probes-Cy5.5-ZEGFR:1907, Alexa680-ZEGFR:1907, SR680-ZEGFR:1907, and 800CW
      ZEGFR:1907. The EGFR binding property and specificity of the four NIR fluorescent
      Affibody probes were studied by fluorescence microscopy using high EGFR
      expressing A431 cells and low expressing MCF7 cells. The binding affinities of
      the probes (KD) to EGFR were further determined by flow cytometry. In vivo
      optical imaging of the four probes was performed in the mice bearing subcutaneous
      A431 tumors. RESULTS: The four NIR optical probes were prepared in high purity.
      In vitro cell imaging studies demonstrated that all of them could specifically
      bind to EGFR positive A431 cells while showing minimum uptake in low EGFR
      expressing MCF7 cells. Flow cytometry showed that Cy5.5-ZEGFR:1907 and Alexa680
      ZEGFR:1907 possessed high binding affinity in low nanomolar range (43.6 +/- 8.4
      and 28.3 +/- 4.9, respectively). In vivo optical imaging of the four probes
      revealed that they all showed fast tumor targeting ability and good tumor-to
      normal tissue contrast as early as 0.5 h postinjection (p.i.). The tumor-to
      normal tissue ratio reached a peak at 2 to 4 h p.i. by regional of interest (ROI)
      analysis of images. Ex vivo studies further demonstrated that the four probes had
      high tumor uptakes. Particularly, Cy5.5-ZEGFR:1907 and Alex680-ZEGFR:1907
      displayed higher tumor-to-normal tissue ratios than those of the other two
      probes. CONCLUSION: This work demonstrates that Affibody proteins can be modified
      with different NIR fluorescent dyes and used for imaging of EGFR expressing
      tumors. Different NIR fluorescent dyes have variable impact on the in vitro
      binding and in vivo performance of the resulting Affibody based probes.
      Therefore, selection of an appropriate NIRF label is important for optical probe
      development. The probes developed are promising for further tumor imaging
      applications and clinical translation. Particularly, Alex680-ZEGFR:1907 and Cy5.5
      ZEGFR:1907 are excellent candidates as EGFR-targeted probes for optical imaging.

PMID- 22621239
TI  - Antimicrobial activity of wild mushroom extracts against clinical isolates
      resistant to different antibiotics.
AB  - AIMS: This work aimed to screen the antimicrobial activity of aqueous methanolic
      extracts of 13 mushroom species, collected in Braganca, against several clinical
      isolates obtained in Hospital Center of Tras-os-Montes and Alto Douro, Portugal.
      METHODS AND RESULTS: Microdilution method was used to determine the minimum
      inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC).
      MIC results showed that Russula delica and Fistulina hepatica extracts inhibited
      the growth of gram-negative (Escherichia coli, Morganella morganni and
      Pasteurella multocida) and gram-positive (Staphylococcus aureus, MRSA,
      Enterococcus faecalis, Listeria monocytogenes, Streptococcus agalactiae and
      Streptococcus pyogenes) bacteria. A bactericide effect of both extracts was
      observed in Past. multocida, Strep. agalactiae and Strep. pyogenes with MBC of
      20, 10 and 5 mg ml-1, respectively. Lepista nuda extract exhibited a bactericide
      effect upon Past. multocida at 5 mg ml-1 and inhibited Proteus mirabilis at 20 mg
      ml-1. Ramaria botrytis extract showed activity against Enterococcus faecalis and
      L. monocytogenes, being bactericide for Past. multocida, Strep. agalactiae (MBCs
      20 mg ml-1) and Strep. pyogenes (MBC 10 mg ml-1). Leucopaxillus giganteus extract
      inhibited the growth of E. coli and Pr. mirabilis, being bactericide for Past.
      multocida, Strep. pyogenes and Strep. agalactiae. CONCLUSIONS: Fistulina
      hepatica, R. botrytis and R. delica are the most promising species as
      antimicrobial agents. SIGNIFICANCE AND IMPACT OF THE STUDY: Mushroom extracts
      could be an alternative as antimicrobials against pathogenic micro-organisms
      resistant to conventional treatments.

PMID- 22621240
TI  - Chiari III Malformation: a rare case with review of literature.
AB  - The Chiari Malformation is a neural tube defect involving the posterior cranial
      fossa and the hind brain, characterized by herniation of the posterior fossa
      contents below the level of the foramen magnum. Four types were described by Hans
      Chiari in the late 19th century. Of these, Type III is exceedingly rare. We
      report the case of Chiari III malformation in a 24-week fetus by the integration
      of radiologic and autopsy findings which was conspicuous by the absence of high
      cervical spina bifida and the presence of occipital squama defect.

PMID- 22621241
TI  - Quantitative proteomic analysis of intracytoplasmic membrane development in
      Rhodobacter sphaeroides.
AB  - The purple phototrophic bacteria elaborate a specialized intracytoplasmic
      membrane (ICM) system for the conversion of solar energy to ATP. Previous
      radiolabelling and ultrastructural experiments have shown that ICM assembly in
      Rhodobacter sphaeroides is initiated at indentations of the cytoplasmic membrane,
      termed UPB. Here, we report proteomic analyses of precursor (UPB) and mature
      (ICM) fractions. Qualitative data identified 387 proteins, only 43 of which were
      found in the ICM, reflecting its specialized role within the cell, the conversion
      of light into chemical energy; 236 proteins were found in the significantly more
      complex UPB proteome. Metabolic labelling was used to quantify the relative
      distribution of 173 proteins between the UPB and ICM fractions. Quantification
      reveals new information on assembly of the RC-LH1-PufX, ATP synthase and NAD(P)H
      transhydrogenase complexes, as well as showing that the UPB is enriched in
      enzymes for lipid, carbohydrate and amino acid metabolism, tetrapyrrole
      biosynthesis and proteins representing a wide range of other metabolic and
      biosynthetic functions. Proteins involved in light harvesting, photochemistry,
      electron transport and ATP synthesis are all enriched in ICM, consistent with the
      spatial proximity of energy capturing and transducing functions. These data
      provide further support to the developmental precursor-product relationship
      between UPB and ICM.

PMID- 22621242
TI  - A region-based segmentation of tumour from brain CT images using nonlinear
      support vector machine classifier.
AB  - The proposed system provides new textural information for segmenting tumours,
      efficiently and accurately and with less computational time, from benign and
      malignant tumour images, especially in smaller dimensions of tumour regions of
      computed tomography (CT) images. Region-based segmentation of tumour from brain
      CT image data is an important but time-consuming task performed manually by
      medical experts. The objective of this work is to segment brain tumour from CT
      images using combined grey and texture features with new edge features and
      nonlinear support vector machine (SVM) classifier. The selected optimal features
      are used to model and train the nonlinear SVM classifier to segment the tumour
      from computed tomography images and the segmentation accuracies are evaluated for
      each slice of the tumour image. The method is applied on real data of 80 benign,
      malignant tumour images. The results are compared with the radiologist labelled
      ground truth. Quantitative analysis between ground truth and the segmented tumour
      is presented in terms of segmentation accuracy and the overlap similarity measure
      dice metric. From the analysis and performance measures such as segmentation
      accuracy and dice metric, it is inferred that better segmentation accuracy and
      higher dice metric are achieved with the normalized cut segmentation method than
      with the fuzzy c-means clustering method.

PMID- 22621243
TI  - Studies on the effect of solvents on self-assembled monolayers formed from
      organophosphonic acids on indium tin oxide.
AB  - The preparation of self-assembled monolayers (SAMs) of organophosphonic acids on
      indium tin oxide (ITO) surfaces from different solvents (triethylamine, ethyl
      ether, tetrahydofuran (THF), pyridine, acetone, methanol, acetonitrile, dimethyl
      sulfoxide (DMSO), or water) has been performed with some significant differences
      observed. Cyclic voltammetry (CV), X-ray photoelectron spectroscopy (XPS),
      scanning tunneling microscopy (STM), and contact angle measurement demonstrated
      that the quality of SAMs depends critically on the choice of solvents. Higher
      density, more stable monolayers were formed from solvents with low dielectric
      constants and weak interactions with the ITO. It was concluded low dielectric
      solvents that were inert to the ITO gave monolayers that were more stable with a
      higher density of surface bound molecules because higher dielectric constant
      solvents and solvents that coordinate with the surface disrupted SAM formation.

PMID- 22621244
TI  - The development of HEPT-type HIV non-nucleoside reverse transcriptase inhibitors
      and its implications for DABO family.
AB  - 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) was discovered as the
      first HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) in 1989. The
      research on HEPT derivatives (HEPTs) has been lasted for more than 20 years and
      HEPT family is probably the most investigated NNRTI. Extensive molecular
      modifications on HEPT have led to many highly potent compounds with broad
      resistance spectrum and optimal pharmacokinetic profiles. Moreover, X
      crystallographic studies of HEPTs/RT complexes revealed the binding mode of HEPTs
      and the action mechanism of NNRTI, which has greatly facilitated the design of
      novel NNRTIs. Recently, the development of HEPTs was accelerated by the
      application of the "follow-on"-based chemical evolution strategies, such as
      designed multiple ligands (DMLs) and molecular hybridization (MH). Herein, this
      article will provide an insight into the development of HEPTs, including
      structural modifications, crystal structure of RT complexed with HEPTs and its
      structure-activity relationship (SAR). Additionally, this review also covers the
      emerging HEPT related dual inhibitors and HEPT-pyridinone hybrids, as well as the
      contributions of HEPTs to the development of dihydro-alkoxy-benzyl-oxopyrimidine
      (DABO) family, thus highlighting the importance of HEPTs on the development of
      NNRTIs.

PMID- 22621245
TI  - Use of human umbilical cord blood mononuclear cells to prevent perinatal brain
      injury: a preclinical study.
AB  - Cerebral palsy (CP) is the most frequent neurological disorder associated with
      perinatal injury of the developing brain. Major brain lesions associated with CP
      are white matter damage (WMD) in preterm infants and cortico-subcortical lesions
      in term newborns. Cell therapy is considered promising for the repair of brain
      damage. Human umbilical cord blood mononuclear cells (hUCB-MNCs) are a rich
      source of various stem cells that could be of interest in repairing perinatal
      brain damage. Our goal was to investigate the potential of hUCB-MNCs to prevent
      or repair brain lesions in an animal model of excitotoxic brain injury. We
      induced neonatal brain lesions using intracranial injections of ibotenate, a
      glutamate agonist, in 5-day-old rat pups. hUCB-MNCs were injected either
      intraperitoneally (i.p.) or intravenously (i.v.) soon or 24 h after ibotenate
      injection, and their neurological effects were assessed using histology and
      immunohistochemistry. hUCB-MNCs injected i.p. did not reach the systemic
      circulation but high amounts induced a significant systemic inflammatory response
      and increased the WMD induced by the excitotoxic insult. This effect was
      associated with a significant 40% increase in microglial activation around the
      white matter lesion. hUCB-MNCs injected i.v. soon or 24 h after the excitotoxic
      insult did not affect lesion size, microglial activation, astroglial cell
      density, or cell proliferation within the developing white matter or cortical
      plate at any concentration used. We demonstrated that hUCB-MNCs could not
      integrate into the developing brain or promote subsequent repair in most
      conditions tested. We found that the intraperitoneal injection of high amounts of
      hUCB-MNCs aggravated WMD and was associated with systemic inflammation.

PMID- 22621247
TI  - Discolouration potential of endodontic procedures and materials: a review.
AB  - Advances in endodontic materials and techniques are at the forefront of
      endodontic research. Despite continuous improvements, tooth discolouration,
      especially in anterior teeth, is considered an undesirable consequence following
      endodontic treatment as it creates a range of aesthetic problems. This article
      aims to discuss the intrinsic and internalized tooth discolouration caused by
      endodontic procedures, and to address the discolouration potential of materials
      used during root canal treatment, including root canal irrigants, intra-canal
      medicaments, endodontic and post-endodontic filling materials. In addition, the
      discolouration patterns caused by combined endodontic and nonendodontic
      aetiological factors are discussed. The recommended guidelines that should be
      followed by dental practitioners to prevent and manage tooth discolouration are
      also outlined.

PMID- 22621246
TI  - Transcriptome-based identification of antioxidative gene expression after fish
      oil supplementation in normo- and dyslipidemic men.
AB  - BACKGROUND: The beneficial effects of omega-3 polyunsaturated fatty acids (n-3
      PUFAs), especially in dyslipidemic subjects with a high risk of cardiovascular
      disease, are widely described in the literature. A lot of effects of n-3 PUFAs
      and their oxidized metabolites are triggered by regulating the expression of
      genes. Currently, it is uncertain if the administration of n-3 PUFAs results in
      different expression changes of genes related to antioxidative mechanisms in
      normo- and dyslipidemic subjects, which may partly explain their cardioprotective
      effects. The aim of this study was to investigate the effects of n-3 PUFA
      supplementation on expression changes of genes involved in oxidative processes.
      METHODS: Ten normo- and ten dyslipidemic men were supplemented for twelve weeks
      with fish oil capsules, providing 1.14 g docosahexaenoic acid and 1.56 g
      eicosapentaenoic acid. Gene expression levels were determined by whole genome
      microarray analysis and quantitative real-time polymerase chain reaction (qRT
      PCR). RESULTS: Using microarrays, we discovered an increased expression of
      antioxidative enzymes and a decreased expression of pro-oxidative and tissue
      enzymes, such as cytochrome P450 enzymes and matrix metalloproteinases, in both
      normo- and dyslipidemic men. An up-regulation of catalase and heme oxigenase 2 in
      both normo- and dyslipidemic subjects and an up-regulation of cytochrome P450
      enzyme 1A2 only in dyslipidemic subjects could be observed by qRT-PCR analysis.
      CONCLUSIONS: Supplementation of normo- and dyslipidemic subjects with n-3 PUFAs
      changed the expression of genes related to oxidative processes, which may suggest
      antioxidative and potential cardioprotective effects of n-3 PUFAs. Further
      studies combining genetic and metabolic endpoints are needed to verify the
      regulative effects of n-3 PUFAs in antioxidative gene expression to better
      understand their beneficial effects in health and disease prevention. TRIAL
      REGISTRATION: ClinicalTrials.gov (ID: NCT01089231).

PMID- 22621249
TI  - Surprisingly favorable outcome in a patient with Goodpasture's disease.

PMID- 22621248
TI  - Aberrant CD200/CD200R1 expression and function in systemic lupus erythematosus
      contributes to abnormal T-cell responsiveness and dendritic cell activity.
AB  - INTRODUCTION: CD200 is a type I transmembrane glycoprotein that can regulate the
      activation threshold of inflammatory immune responses, polarize cytokine
      production, and maintain immune homeostasis. We therefore evaluated the
      functional status of CD200/CD200 receptor 1 (CD200R1) interactions in subjects
      with systemic lupus erythematosus (SLE). METHODS: Serum CD200 level was detected
      by ELISA. The expression of CD200/CD200R1 by CD4+ T cells and dendritic cells
      (DCs) was examined by flow cytometry, and then compared between SLE patients and
      healthy controls. Peripheral blood mononuclear cells were stained with
      carboxyfluorescein diacetate succinimidyl ester and annexin V/propidium iodide
      for evaluation of the effect of CD200 on cell proliferation and apoptosis. In
      addition, the effect of CD200 on DC function was determined by transwell
      migration assay as well as by measurement of binding and phagocytosis of
      apoptotic cells. RESULTS: In SLE patients, the number of CD200+ cells and the
      level of soluble CD200 were significantly higher than in healthy controls,
      whereas the expression of CD200R1 by CD4+ T cells and DCs was decreased.
      Furthermore, the increased CD200 expression by early apoptotic cells contributed
      to their diminished binding and phagocytosis by DCs in SLE. Importantly, the
      engagement of CD200 receptor on CD4+ T cells with CD200-Fc fusion protein in
      vitro reduced the differentiation of T-helper type 17 cells and reversed the
      defective induction of CD4+CD25highFoxP3+ T cells by transforming growth factor
      beta in SLE patients. Conversely, blockade of CD200-CD200R1 interaction with anti
      CD200R1 antibody promoted CD4+ T-cell proliferation. CONCLUSION: CD200 and
      CD200R1 expression and function are abnormal in SLE and may contribute to the
      immunologic abnormalities in SLE.

PMID- 22621250
TI  - Utility of the frontonasal suture for estimating age at death in human skeletal
      remains.
AB  - This project evaluated the utility of the frontonasal suture for estimating age
      at death. Utilizing human remains of known age at death with varying degrees of
      fusion, curated at the American Museum of Natural History in New York City and
      the Smithsonian Institution's National Museum of Natural History in Washington,
      DC, data were collected from the ectocranial surface of 522 crania; 68 of these
      were sagittally sectioned, allowing collection of internal data and observation
      of suture closure through the bone. Degree of ectocranial suture closure does not
      significantly predict age, even when sex and ancestry are accounted for. Suture
      closure progression data were converted into a Hershkovitz ratio (sum of the
      measurement of open portion divided by the total suture length), and regression
      models demonstrate that the effect of age accounts for only 13% of variation in
      suture closure.

PMID- 22621251
TI  - Improvements in estimated entropies and related thermodynamic data for aqueous
      metal ions.
AB  - New estimated standard entropies for some aqueous metal ions are obtained by
      taking account of magnetic and symmetry contributions. By combining them with an
      analysis of literature data, improved experimental and estimated values are
      derived for the standard enthalpies and Gibbs energies of formation of the
      aqueous ions of titanium, vanadium, chromium, manganese, cerium, and
      praseodymium. Separate entropy correlations are used for each primary
      coordination number, and the size dependence is represented by the reciprocal of
      the metal-oxygen distance in that coordination. The new scheme is consistent with
      recent work on the coordination of Hg(2+)(aq), Pb(2+)(aq), and tripositive rare
      earth ions. It differs from its predecessors in indicating a larger variation of
      the standard molar entropies of aqueous ions with coordination number. The value
      of S(Theta)(Be(2+), aq) is discussed in this context.

PMID- 22621252
TI  - Fluoroscopically guided balloon dilatation for the treatment of achalasia: long
      term outcomes.
AB  - To report the immediate and long-term outcomes following the fluoroscopically
      guided balloon dilatations performed in our department for the treatment of
      achalasia. We reviewed retrospectively all patients that underwent a
      fluoroscopically guided balloon dilatation because of achalasia in our department
      between April 2007 and September 2010. The follow-up was performed by interviews
      and/or investigation of the patient's medical and imaging records. The primary
      endpoints of the study were technical success, clinical success, major
      complication rates, and repeat dilatation rates because of recurrence of clinical
      symptomatology. Secondary endpoints were the rate of minor complications and the
      dilatation-free interval. Various parameters that could affect the clinical
      outcome were also analyzed. Thirty-nine consecutive patients (20 female) with a
      mean age 44 +/- 17 years underwent 69 dilatations, while 10/39 (25.6%) patients
      had a history of a previous laparoscopic myotomy. The most common symptom was
      dysphagia (64/69, 92.7%), while regurgitation and/or retrosternal pain were
      present in 12/39 (30.7%) and 9/39 (23%) of the cases, respectively. Technical
      success was achieved in 98.5% (68/69). There were no procedure-related major
      complications. The mean balloon diameter used was 30 +/- 3.9 mm, and the mean
      period of follow-up was 27.7 +/- 16.0 months. Excellent or good initial responses
      were noted in 54/66 cases (81.8%). A repeated dilatation to deal with recurrence
      of symptoms was performed in 69.4% of the cases (25/36). In the majority of the
      cases, two dilatations were needed in order to achieve long-term relief from
      symptoms. A dilatation-free interval of 4 years was observed in 26.4%. Clinical
      success was achieved in 30/36 patients (83.3%). Subgroup analysis did not detect
      significantly different recurrence rates in patients with and without previous
      laparoscopic myotomy (50% vs. 69% respectively), those of young age (75% < 21
      years vs. 68.8% > 21 years), and male gender (71.4% male vs. 55.0% females). The
      high redilatation rate was attributed to the utilization of smaller balloons by
      less experienced operators. Fluoroscopically guided balloon dilatation is a safe
      and effective method for the treatment of achalasia. Young age and prior Heller's
      laparoscopic myotomy were not associated with increased rates of recurrence rate
      or clinical failure.

PMID- 22621253
TI  - What are the standards of care for cauda equina syndrome?

PMID- 22621254
TI  - The effect of first-in-class small molecule RhoA inhibitor, HL07, on the
      phenylephrine-induced artery contraction.
AB  - The RhoA/ROCK inhibitors have emerged as a new promising treatment for
      cardiovascular diseases. Recently, we first reported a series of first-in-class
      small molecular RhoA inhibitors and a chemical compound named HL07 showed high
      RhoA inhibition activities. In this study, we aimed to explore the
      pharmacological effect and possible mechanism of HL07 on agonists-induced
      vasoconstriction. Results showed that 1) in rat thoracic aorta (TA) rings,
      HL07(0~180 umol/L) effectively inhibited phenylephrine (PE)-induced contraction
      in concentration-dependent manner , whereas the half maximal inhibitory
      concentration (IC(50)) being 156.93 umol/L, while it produced weak inhibition on
      high-K(+)-induced contraction. Furthermore, in the presence of nifedipine and
      thapsigargin (Nif/TSG), HL07 had a comparable degree of inhibition on PE-induced
      contraction with IC(50)=149.52 umol/L; especially at the concentration (0~150
      umol/L), the inhibition was greater than the inhibition in absence of Nif/TSG (P
      < 0.01). In addition, HL07 displayed greater inhibition on pulmonary artery (PA)
      rings (IC(50)=134.97 umol/L) than on TA rings. 2) HL07 potently blocked RhoA
      activation stimulated by PE in concentration-dependent manner in human
      cerebrovascular smooth muscle cells (HBVSMCs), when HL07 at 10, 2, 0.25 umol/L,
      the corresponding inhibition rates were 64 +/- 5%, 42 +/- 7%, 31 +/- 5%,
      respectively; and at the same concentrations, HL07 had no significant effect on
      RhoA mRNA level. 3) In HBVSMCs, RhoA activity was increased by pre-incubating
      with GNP, but HL07 showed inhibitory effect on this tendency. These results
      indicate that HL07 produces significant inhibitory effects on PE-induced vascular
      smooth muscle contraction. The inhibitory effects of HL07 were mainly contributed
      to its inhibition on RhoA/Rho-kinase pathway through blocking RhoA activation,
      and the binding affinities of HL07 for RhoA preference over the GNP might be
      responsible for the inhibition of HL07 on RhoA activity.

PMID- 22621255
TI  - Stress amongst nurses working in a healthcare telephone-advice service:
      relationship with job satisfaction, intention to leave, sickness absence, and
      performance.
AB  - AIMS: This paper is a report of a study, which assessed levels of stress amongst
      nurses working in a healthcare telephone-advice service. We explored whether
      stress related to performance, sickness absence, and intention to leave.
      BACKGROUND: Nurses report high levels of stress, as do call-centre workers. The
      emergence of telephone health advice services means many nurses now work in call
      centres, doing work that differs markedly from traditional nursing roles. Stress
      associated with these roles could have implications for nurses, patients, and
      service provision. DESIGN: This paper reports cross-sectional survey results. The
      design of the overall study included longitudinal elements. METHOD: A
      comprehensive study of stress was conducted amongst nurses working for a
      telephone-advice service in Scotland (2008-2010). All nurse-advisors were
      approached by letter and invited to participate. A total of 152 participants
      (33%) completed a questionnaire including General Health Questionnaire-12, Work
      Family Conflict Questionnaire, Job Satisfaction Scale and a measure of intention
      to leave the telephone-advice service and rated the perceived stress of 2 working
      shifts. Nurses' employers provided data on sickness absence and performance.
      RESULTS: Overall levels of psychological distress were similar to those found
      amongst Scottish women generally. In multiple regression, work-family conflict
      was identified as a significant predictor of job satisfaction and intention to
      leave, and significantly related to sickness absence. There were significant
      correlations between General Health Questionnaire scores and perceived stress of
      shifts and some performance measures. CONCLUSIONS: Work-family conflict is a
      significant predictor of job satisfaction, intention to leave, and sickness
      absence amongst telephone helpline nurses. Minimizing the impact of nurses' work
      on their home lives might reduce turnover and sickness absence.

PMID- 22621256
TI  - Developing histone deacetylase inhibitors in the therapeutic armamentarium of
      pancreatic adenocarcinoma.
AB  - INTRODUCTION: Histone deacetylases (HDACs) are commonly dysregulated in
      pancreatic adenocarcinoma (PA) and have a central role in the development and
      progression of the disease. HDAC is a family of enzymes involved in deacetylation
      of lysine residues on histone and non-histone proteins. Deacetylation of histone
      proteins leads to compaction of the DNA/histone complex resulting in inhibition
      of gene expression. Deacetylation of non-histone proteins can affect the
      stability and function of key proteins leading to dysregulation of cellular
      signaling pathways. HDAC inhibitors have been shown to potentiate the
      antiproliferative and proapoptotic effects of several cytotoxic agents, in vitro
      and in vivo PA xenograft models. AREAS COVERED: The areas covered include the
      biology and function of the HDAC isoenzymes and their significant role in
      multiple oncogenic pathways in PA. Preclinical and clinical trials evaluating
      HDAC inhibitors are also reviewed. EXPERT OPINION: Despite discouraging early
      phase clinical trials evaluating HDAC inhibitors in PA, this strategy deserves
      further evaluation guided by better preclinical studies in identifying the role
      of specific HDAC isoenzyme inhibitors in PA. Evaluation of the effects of HDAC
      inhibitors on PA stem cell function and epithelial to mesenchymal transformation
      is also an evolving area that holds future potential for these agents. Such
      preclinical studies will yield insight into the functionality of HDAC isoenzymes,
      which can then be translated into rationally designed clinical trials. One such
      strategy could focus on HDAC inhibition employed in combination with proteasome
      inhibition targeting the aggresome pathway in PA.

PMID- 22621258
TI  - Iron-catalyzed 2-arylbenzoxazole formation from o-nitrophenols and benzylic
      alcohols.
AB  - The iron-catalyzed 2-arylbenzoxazole formation from o-nitrophenols and benzylic
      alcohols using hydrogen transfer is described. Various 2-arylbenzoxazoles were
      selectively obtained in good to excellent yields. The reaction tolerated a wide
      range of functionalities. The alcohol oxidation, nitro reduction, condensation,
      and dehydrogenation were realized in a cascade without external reducing reagent
      and oxidant.

PMID- 22621257
TI  - Development of a novel long-lived immunoPET tracer for monitoring lymphoma
      therapy in a humanized transgenic mouse model.
AB  - Positron emission tomography (PET) is an attractive imaging tool to localize and
      quantify tracer biodistribution. ImmunoPET with an intact mAb typically requires
      two to four days to achieve optimized tumor-to-normal ratios. Thus, a positron
      emitter with a half-life of two to four days such as zirconium-89 [(89)Zr] (t1/2:
      78.4 h) is ideal. We have developed an antibody-based, long-lived immunoPET
      tracer (89)Zr-Desferrioxamine-p-SCN (Df-Bz-NCS)-rituximab (Zr-iPET) to image
      tumor for longer durations in a humanized CD20-expressing transgenic mouse model.
      To optimize the radiolabeling efficiency of (89)Zr with Df-Bz-rituximab, multiple
      radiolabelings were performed. Radiochemical yield, purity, immunoreactivity, and
      stability assays were carried out to characterize the Zr-iPET for chemical and
      biological integrity. This tracer was used to image transgenic mice that express
      the human CD20 on their B cells (huCD20TM). Each huCD20TM mouse received a 7.4
      MBq/dose. One group (n = 3) received a 2 mg/kg predose (blocking) of cold
      rituximab 2 h prior to (89)Zr-iPET; the other group (n = 3) had no predose
      (nonblocking). Small animal PET/CT was used to image mice at 1, 4, 24, 48, 72,
      and 120 h. Quality assurance of the (89)Zr-iPET demonstrated NCS-Bz-Df: antibody
      ratio (c/a: 1.5 +/- 0.31), specific activity (0.44-1.64 TBq/mol), radiochemical
      yield (>70%), and purity (>98%). The Zr-iPET immunoreactivity was >80%. At 120 h,
      Zr-iPET uptake (% ID/g) as mean +/- STD for blocking and nonblocking groups in
      spleen was 3.2 +/- 0.1% and 83.3 +/- 2.0% (p value <0.0013.). Liver uptake was
      1.32 +/- 0.05% and 0.61 +/- 0.001% (p value <0.0128) for blocking and
      nonblocking, respectively. The small animal PET/CT image shows the spleen
      specific uptake of Zr-iPET in mice at 120 h after tracer injection. Compared to
      the liver, the spleen specific uptake of Zr-iPET is very high due to the
      expression of huCD20. We optimized the radiolabeling efficiency of (89)Zr with Df
      Bz-rituximab. These radioimmunoconjugate lots were stable up to 5 days in serum
      in vitro. The present study showed that (89)Zr is well-suited for mAbs to image
      cancer over an extended period of time (up to 5 days). 

PMID- 22621259
TI  - Temperature-dependent competition between adsorption and aggregation of a
      cellulose ether--simultaneous use of optical and acoustical techniques for
      investigating surface properties.
AB  - Adsorption of the temperature-responsive polymer hydroxypropylmethylcellulose
      (HPMC) from an aqueous solution onto hydrophobized silica was followed well above
      the bulk instability temperature (T(2)) in temperature cycle experiments. Two
      complementary techniques, QCM-D and ellipsometry, were utilized simultaneously to
      probe the same substrate immersed in polymer solution. The interfacial processes
      were correlated with changes in polymer aggregation and viscosity of polymer
      solutions, as monitored by light scattering and rheological measurements. The
      simultaneous use of ellipsometry and QCM-D, and the possibility to follow layer
      properties up to 80  degrees C, well above the T(2) temperature, are both novel
      developments. A moderate increase in adsorbed amount with temperature was found
      below T(2), whereas a significant increase in the adsorbed mass and changes in
      layer properties were observed around the T(2) temperature where the bulk
      viscosity increases significantly. Thus, there is a clear correlation between
      transition temperatures in the adsorbed layer and in bulk solution, and we
      discuss this in relation to a newly proposed model that considers competition
      between aggregation and adsorption/deposition. A much larger temperature response
      above the T(2) temperature was found for adsorbed layers of HPMC than for layers
      of methyl cellulose. Possible reasons for this are discussed.

PMID- 22621260
TI  - Both the middle temporal gyrus and the ventral anterior temporal area are crucial
      for multimodal semantic processing: distortion-corrected fMRI evidence for a
      double gradient of information convergence in the temporal lobes.
AB  - Most contemporary theories of semantic memory assume that concepts are formed
      from the distillation of information arising in distinct sensory and verbal
      modalities. The neural basis of this distillation or convergence of information
      was the focus of this study. Specifically, we explored two commonly posed
      hypotheses: (a) that the human middle temporal gyrus (MTG) provides a crucial
      semantic interface given the fact that it interposes auditory and visual
      processing streams and (b) that the anterior temporal region-especially its
      ventral surface (vATL)-provides a critical region for the multimodal integration
      of information. By utilizing distortion-corrected fMRI and an established
      semantic association assessment (commonly used in neuropsychological
      investigations), we compared the activation patterns observed for both the verbal
      and nonverbal versions of the same task. The results are consistent with the two
      hypotheses simultaneously: Both MTG and vATL are activated in common for word and
      picture semantic processing. Additional planned, ROI analyses show that this
      result follows from two principal axes of convergence in the temporal lobe: both
      lateral (toward MTG) and longitudinal (toward the anterior temporal lobe).

PMID- 22621261
TI  - Effects of category learning on neural sensitivity to non-native phonetic
      categories.
AB  - Categorical perception, an increased sensitivity to between- compared with within
      category contrasts, is a stable property of native speech perception that emerges
      as language matures. Although recent research suggests that categorical responses
      to speech sounds can be found in left prefrontal as well as temporo-parietal
      areas, it is unclear how the neural system develops heightened sensitivity to
      between-category contrasts. In the current study, two groups of adult
      participants were trained to categorize speech sounds taken from a
      dental/retroflex/velar continuum according to two different boundary locations.
      Behavioral results suggest that for successful learners, categorization training
      led to increased discrimination accuracy for between-category contrasts with no
      concomitant increase for within-category contrasts. Neural responses to the
      learned category schemes were measured using a short-interval habituation design
      during fMRI scanning. Whereas both inferior frontal and temporal regions showed
      sensitivity to phonetic contrasts sampled from the continuum, only the bilateral
      middle frontal gyri exhibited a pattern consistent with encoding of the learned
      category scheme. Taken together, these results support a view in which top-down
      information about category membership may reshape perceptual sensitivities via
      attention or executive mechanisms in the frontal lobes.

PMID- 22621262
TI  - Hippocampal-prefrontal engagement and dynamic causal interactions in the
      maturation of children's fact retrieval.
AB  - Children's gains in problem-solving skills during the elementary school years are
      characterized by shifts in the mix of problem-solving approaches, with
      inefficient procedural strategies being gradually replaced with direct retrieval
      of domain-relevant facts. We used a well-established procedure for strategy
      assessment during arithmetic problem solving to investigate the neural basis of
      this critical transition. We indexed behavioral strategy use by focusing on the
      retrieval frequency and examined changes in brain activity and connectivity
      associated with retrieval fluency during arithmetic problem solving in second-
      and third-grade (7- to 9-year-old) children. Children with higher retrieval
      fluency showed elevated signal in the right hippocampus, parahippocampal gyrus
      (PHG), lingual gyrus (LG), fusiform gyrus (FG), left ventrolateral PFC (VLPFC),
      bilateral dorsolateral PFC (DLPFC), and posterior angular gyrus. Critically,
      these effects were not confounded by individual differences in problem-solving
      speed or accuracy. Psychophysiological interaction analysis revealed significant
      effective connectivity of the right hippocampus with bilateral VLPFC and DLPFC
      during arithmetic problem solving. Dynamic causal modeling analysis revealed
      strong bidirectional interactions between the hippocampus and the left VLPFC and
      DLPFC. Furthermore, causal influences from the left VLPFC to the hippocampus
      served as the main top-down component, whereas causal influences from the
      hippocampus to the left DLPFC served as the main bottom-up component of this
      retrieval network. Our study highlights the contribution of hippocampal
      prefrontal circuits to the early development of retrieval fluency in arithmetic
      problem solving and provides a novel framework for studying dynamic developmental
      processes that accompany children's development of problem-solving skills.

PMID- 22621264
TI  - Visual and auditory cue integration for the generation of saccadic eye movements
      in monkeys and lever pressing in humans.
AB  - This study examined how effectively visual and auditory cues can be integrated in
      the brain for the generation of motor responses. The latencies with which
      saccadic eye movements are produced in humans and monkeys form, under certain
      conditions, a bimodal distribution, the first mode of which has been termed
      express saccades. In humans, a much higher percentage of express saccades is
      generated when both visual and auditory cues are provided compared with the
      single presentation of these cues [H. C. Hughes et al. (1994) J. Exp. Psychol.
      Hum. Percept. Perform., 20, 131-153]. In this study, we addressed two questions:
      first, do monkeys also integrate visual and auditory cues for express saccade
      generation as do humans and second, does such integration take place in humans
      when, instead of eye movements, the task is to press levers with fingers? Our
      results show that (i) in monkeys, as in humans, the combined visual and auditory
      cues generate a much higher percentage of express saccades than do singly
      presented cues and (ii) the latencies with which levers are pressed by humans are
      shorter when both visual and auditory cues are provided compared with the
      presentation of single cues, but the distribution in all cases is unimodal;
      response latencies in the express range seen in the execution of saccadic eye
      movements are not obtained with lever pressing.

PMID- 22621263
TI  - Differential brain activity during emotional versus nonemotional reversal
      learning.
AB  - The ability to change an established stimulus-behavior association based on
      feedback is critical for adaptive social behaviors. This ability has been
      examined in reversal learning tasks, where participants first learn a stimulus
      response association (e.g., select a particular object to get a reward) and then
      need to alter their response when reinforcement contingencies change. Although
      substantial evidence demonstrates that the OFC is a critical region for reversal
      learning, previous studies have not distinguished reversal learning for emotional
      associations from neutral associations. The current study examined whether OFC
      plays similar roles in emotional versus neutral reversal learning. The OFC showed
      greater activity during reversals of stimulus-outcome associations for negative
      outcomes than for neutral outcomes. Similar OFC activity was also observed during
      reversals involving positive outcomes. Furthermore, OFC activity is more
      inversely correlated with amygdala activity during negative reversals than during
      neutral reversals. Overall, our results indicate that the OFC is more activated
      by emotional than neutral reversal learning and that OFC's interactions with the
      amygdala are greater for negative than neutral reversal learning.

PMID- 22621265
TI  - Intracellular lipid accumulation inhibitory effect of Weissella koreensis OK1-6
      isolated from Kimchi on differentiating adipocyte.
AB  - AIMS: To investigate the intracellular lipid accumulation inhibitory effect of
      spent culture medium extract and the cytoplasmic fraction of Weissella koreensis
      OK1-6 cells isolated from kimchi in differentiating 3T3-L1 cells. METHODS AND
      RESULTS: Differentiating 3T3-L1 cells were treated with either cytoplasmic
      fraction of W. koreensis OK1-6 cells or its spent media for 4 days. Both the
      spent culture medium extract and cytoplasmic fraction of W. koreensis OK1-6 cells
      significantly decreased the triglyceride concentration and intracellular lipid
      accumulation in the treated groups compared with the control group. The mRNA
      expression levels of C/EBP-alpha, one of the major transcriptional factors
      involved in adipocyte differentiation, were significantly less expressed in 3T3
      L1 cells treated with the spent medium and cytoplasmic fraction. The expressions
      of aP2, fatty acid synthase (FAS) and SREBP1 genes were also decreased
      significantly. CONCLUSIONS: These results suggested that W. koreensis OK1-6 could
      play a crucial role in preventing intracellular lipid accumulation by down
      regulating the expression of adipocyte-specific genes C/EBPalpha, aP2, SREBP1 and
      FAS. SIGNIFICANCE AND IMPACT OF THE STUDY: These results may contribute to
      nutraceutical and food industries in developing probiotic-based therapies for the
      treatment and prevention of obesity.

PMID- 22621266
TI  - Extracting semantically enriched events from biomedical literature.
AB  - BACKGROUND: Research into event-based text mining from the biomedical literature
      has been growing in popularity to facilitate the development of advanced
      biomedical text mining systems. Such technology permits advanced search, which
      goes beyond document or sentence-based retrieval. However, existing event-based
      systems typically ignore additional information within the textual context of
      events that can determine, amongst other things, whether an event represents a
      fact, hypothesis, experimental result or analysis of results, whether it
      describes new or previously reported knowledge, and whether it is speculated or
      negated. We refer to such contextual information as meta-knowledge. The automatic
      recognition of such information can permit the training of systems allowing finer
      grained searching of events according to the meta-knowledge that is associated
      with them. RESULTS: Based on a corpus of 1,000 MEDLINE abstracts, fully manually
      annotated with both events and associated meta-knowledge, we have constructed a
      machine learning-based system that automatically assigns meta-knowledge
      information to events. This system has been integrated into EventMine, a state-of
      the-art event extraction system, in order to create a more advanced system
      (EventMine-MK) that not only extracts events from text automatically, but also
      assigns five different types of meta-knowledge to these events. The meta
      knowledge assignment module of EventMine-MK performs with macro-averaged F-scores
      in the range of 57-87% on the BioNLP'09 Shared Task corpus. EventMine-MK has been
      evaluated on the BioNLP'09 Shared Task subtask of detecting negated and
      speculated events. Our results show that EventMine-MK can outperform other state
      of-the-art systems that participated in this task. CONCLUSIONS: We have
      constructed the first practical system that extracts both events and associated,
      detailed meta-knowledge information from biomedical literature. The automatically
      assigned meta-knowledge information can be used to refine search systems, in
      order to provide an extra search layer beyond entities and assertions, dealing
      with phenomena such as rhetorical intent, speculations, contradictions and
      negations. This finer grained search functionality can assist in several
      important tasks, e.g., database curation (by locating new experimental knowledge)
      and pathway enrichment (by providing information for inference). To allow easy
      integration into text mining systems, EventMine-MK is provided as a UIMA
      component that can be used in the interoperable text mining infrastructure, U
      Compare.

PMID- 22621267
TI  - Future preventive and therapeutic targets for transfusion-related acute lung
      injury.
AB  - Transfusion-related acute lung injury (TRALI) has been the leading cause of
      transfusion-associated death for nearly a decade. Recent TRALI mitigation
      strategies focused on reduction of leukocyte antibodies in high volume plasma
      products appear to be successful in reducing TRALI events and deaths, but
      additional preventive measures are needed. Future possibilities include,
      screening of donors for neutrophil antibodies, processing of blood products to
      reduce or remove biologic response modifiers, and the more judicious use of
      blood. There are currently no specific TRALI therapies. The pathogenesis of TRALI
      and acute lung injury-acute respiratory distress syndrome (ALI-ARDS) is quite
      similar; both involving interactions of activated platelets, neutrophils, and
      pulmonary endothelium resulting in lung damage, capillary leak, and pulmonary
      edema. Greater understanding of these interactions and the key molecules involved
      will lead to development of potential new targets for therapy. In this review,
      future possible preventive measures to further reduce the occurrence of TRALI
      will be discussed, including TRALI caused by biologic response modifiers (BRMs),
      like bioactive lipids and sCD40L, which are not addressed by current preventive
      actions that only target leukocyte antibodies in high-volume plasma products.
      Insights already gained from studies of ALI-ARDS treatments will be summarized
      and discussed as possible therapeutic targets for treatment of patients
      experiencing TRALI.

PMID- 22621268
TI  - Prevention of non-immune mediated transfusion-related acute lung injury; from
      blood bank to patient.
AB  - Transfusion-related acute lung injury (TRALI) is a severe form of pulmonary
      insufficiency induced by transfusion. TRALI is the leading cause of transfusion
      related death, and is caused by the infusion of either anti-leukocyte antibodies
      in plasma containing blood products or neutrophil priming substances that
      accumulate during storage of cellular blood products. Among these neutrophil
      priming substances are bioactive lipids, such as lyso-phosphatidylcholines
      (lysoPCs) and arachidonic acid, soluble CD40L (sCD40L) and possibly other, as yet
      unidentified substances. The accumulation of these substances during cellular
      blood product storage and their role in the induction of "non-immune mediated"
      TRALI pathogenesis are highly relevant for the current debate of the use of
      longer vs. shorter stored blood products. In this review, the accumulation of
      these different substances during storage, as well as their mode of action in
      inducing TRALI are discussed. In addition, different improvements in current
      blood banking procedures to prevent TRALI due to these non-immune mediators will
      be proposed.

PMID- 22621269
TI  - Coagulopathy as a therapeutic target for TRALI: rationale and possible sites of
      action.
AB  - Transfusion-related acute lung injury (TRALI) is a subcategory of acute lung
      injury (ALI). As such, there are many similarities between the syndromes, both
      clinically and pathophysiologically. Pulmonary changes in fibrin turnover have
      emerged as a hallmark of ALI, thereby initiating studies investigating the
      potential of therapeutic interventions aimed at ameliorating this so-called
      pulmonary coagulopathy. Enhanced coagulation and impaired fibrinolysis are
      probably also important features of TRALI. In particular, platelets play an
      important role in mediating injury during a TRALI reaction. In this narrative
      review, the evidence of the role of coagulopathy and platelet activation in TRALI
      is discussed. Given that host risk factors for acquiring TRALI have been
      identified and that there is a time frame in which a preventive strategy in
      patients at risk for TRALI can be executed, preventive strategies are suggested.
      In this review, we discuss potential preventive anticoagulant interventions.

PMID- 22621270
TI  - Platelet-neutrophil interactions as a target for prevention and treatment of
      transfusion-related acute lung injury.
AB  - Transfusion-related acute lung injury (TRALI) is a major cause of morbidity and
      mortality in transfused hosts and like other causes of acute lung injury, there
      is no effective pharmacologic treatment. The pathophysiology of TRALI is still
      being defined, but neutrophils have a major role in the pathogenesis of both
      human and experimental studies. Recently, MHC antibody-based experimental TRALI
      models have revealed that platelets sequester in the lung microvasculature and
      that platelet activation contributes to lung injury. Platelets, in general, have
      been increasingly implicated as major contributors to acute inflammation and
      injury in a variety of diseases. The role of platelets in TRALI may be through
      critical interactions with neutrophils and therapeutically this could present a
      target for pharmacologic intervention. Experimentally, aspirin pre-treatment of
      mice before TRALI is protective from acute lung injury and mortality. Other
      therapeutic interventions could include agents that uncouple neutrophils and
      platelets or prevent aggregation and activation, however targeting platelet
      activation in TRALI is complicated by the presence of bleeding as the indication
      for many transfusions. In conclusion, experimental studies are elucidating the
      role of platelets in acute lung injury and with this new understanding, clinical
      trials of anti-platelet agents should be considered.

PMID- 22621272
TI  - Transfusion-related acute lung injury: an overview.
AB  - This paper will summarize the clinical features of transfusion-related acute lung
      injury (TRALI) before the experimental and clinical literature on the
      pathogenesis of TRALI is reviewed. Several mechanisms by which leukocyte
      antibodies induce TRALI have been unraveled. Significant advances have also been
      made in the field of recipient-related factors that contribute to the development
      of TRALI. In contrast, the pathomechanism behind non-immune TRALI (associated
      with the transfusion of blood components which do not contain antibodies) is less
      well understood, especially since the relevance of mechanisms proposed earlier is
      questioned by recent findings. The diversity of newly described factors
      contributing to TRALI supports the previously proposed threshold model of TRALI,
      and an extension of that model including newly defined multipliers and
      attenuators of TRALI is emerging.

PMID- 22621273
TI  - Prevention of immune-mediated transfusion-related acute lung injury; from
      bloodbank to patient.
AB  - Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion
      related morbidity and mortality. Immune-mediated TRALI is caused by leucocyte and
      neutrophil antibodies in the transfused blood products that react with white
      blood cell antigens of the recipient, hereby inducing endothelial damage and lung
      injury. About two thirds of TRALI cases are thought to be immune-mediated. Both
      Human Leucocyte Antibodies (HLA Class I and II) and Human Neutrophil Antibodies
      (HNA) are involved in TRALI. Most antibodies result from allo-exposure of the
      blood donor, with multiparous donors having the highest incidence of antibodies.
      Detection of anti-leucocyte and anti-neutrophil antibodies is complex and many
      uncertainties still exist regarding the interpretation of the test results. In
      this review we discuss the evidence and effectiveness of measurements to prevent
      immune-mediated TRALI from a bloodbank and bedside perspective. From a bloodbank
      perspective various preventive measures have been implicated. In some countries
      bloodbanks have successfully implemented donor selection strategies, ranging from
      testing of allo-exposed donors for leucocyte antibodies to the exclusion of all
      females from donating high plasma volume products. Another strategy involves
      dilution of antibodies present by pooling of plasma donations of multiple donors.
      From a bedside view, the most important measure to prevent TRALI is to limit
      patients' exposure to allogenic bloodproducts. Furthermore recognition and
      awareness of the syndrome need to be heightened among clinicians.

PMID- 22621271
TI  - Therapeutic options for transfusion related acute lung injury; the potential of
      the G2A receptor.
AB  - Priming of polymorphonuclear leukocytes (PMNs) enhances their adhesion to
      endothelium, the release of their granule content and their production of
      reactive oxygen species. These effects are etiological in transfusion related
      acute lung injury (TRALI) and many clinically important mediators of TRALI prime
      PMNs. A priming activity that develops over time in stored blood products has
      been shown to be due to the accumulation of lysophospatidylcholines (lyso-PCs)
      and has been found to be related clinically to TRALI. Lyso- PCs prime PMNs
      activating the G2A receptor and several inhibitors of this receptor, which could
      potentially be therapeutic in TRALI, have been identified. Recent work has
      described early steps in the signaling from the G2A receptor which has revealed
      potential targets for novel antagonists of lyso-PC mediated priming via G2A.
      Additionally, characterization of the process by which lyso-PCs are generated in
      stored blood products could allow development of inhibitors and additive
      solutions to block their formation in the first place.

PMID- 22621274
TI  - State of the art management of transfusion-related acute lung injury (TRALI).
AB  - Transfusion-Related Acute Lung Injury (TRALI) is the leading cause of transfusion
      related mortality in most developed countries. Despite this fact, well-designed
      investigations on specific management strategies for TRALI are lacking. Indeed,
      current recommendations are primarily based on data extrapolated from trials of
      the histo-pathologically similar Acute Lung Injury and Acute Respiratory Distress
      Syndromes. The cornerstone of TRALI management is supportive care with oxygen
      supplementation and ventilatory assistance when needed. When mechanical
      ventilation is required, attenuating additional ventilator-induced lung injury
      through the avoidance of high tidal volumes and elevated airway pressures, with
      additional measures such as positive end-expiratory pressure to prevent low
      volume shear stress injury, are recommended. The literature is not currently
      sufficient to support either corticosteroids or statins as effective therapies in
      TRALI. Conservative fluid practices are desirable, provided care is taken to
      avoid hypotension. Preventative strategies have shown the most promise in
      mitigating this transfusion-related pulmonary complication. Specifically,
      conservative transfusion practices and deferral of high-plasma component donors
      who have, or at high risk of having, anti-human leukocyte antigen and/or anti
      human neutrophil antigen antibodies have meaningfully impacted the incidence of
      TRALI. Future considerations for patients who are at increased risk for
      developing TRALI may include therapies such as anti-platelet agents and
      alternatives to traditional blood components such as prothrombin complex
      concentrates (PCC). However, these potential TRALI prevention strategies are
      insufficiently studied, have unclear risk/benefit profiles and cannot be
      currently recommended.

PMID- 22621275
TI  - Preventive and therapeutic strategies for transfusion-related acute lung injury.

PMID- 22621276
TI  - Association of tobacco use and periapical pathosis - a systematic review.
AB  - The aim was to review the current evidence regarding an association between
      tobacco use, that is, cigarette smoking, and periapical pathosis. A systematic
      MEDLINE search of articles published prior to October 2011 (4th) was conducted
      using the keywords 'smoking and endodontics OR smoking and periapical index'. The
      study selection, data preparation and validity assessment were conducted by two
      reviewers. Nine studies fulfilled the inclusion criteria and represented data
      from 3008 individuals. The studies differed with respect to (i) study design,
      (ii) radiographic techniques, (iii) assessment of periapical pathosis, (iv)
      classification of smoking characteristics and/or (v) potential confounders
      accounted for in the analyses. Five of six cross-sectional studies revealed a
      significant positive association (OR 1.35-16.8) between periapical pathosis and
      current cigarette smoking. One of three longitudinal studies indicated an
      increased risk (OR 1.7) of root treated teeth for current smokers. The
      substantial heterogeneity of the included studies limited their interpretation.
      Further, well-designed studies are required to investigate the association
      between tobacco use and periapical pathosis.

PMID- 22621277
TI  - A comparison of histomorphometric data collection methods.
AB  - Although many variables that skeletal biologists examine have been standardized,
      the actual techniques used to collect these data from bone thin sections vary.
      This project compares different methods of obtaining data (relative cortical area
      values) for histomorphometric research. One visual and three digital methods of
      histomorphometric data collection are compared: (i) Merz microscopic eyepiece
      counting reticule, (ii) flatbed scanner, (iii) overlaying multiple images of a
      thin section, and (iv) digital SLR camera with macro settings. The discussion
      includes a comparison of usability factors such as cost, time, user-experience,
      and ease-of-use, which vary for each method. Values from the different methods
      are compared using ANOVA tests to evaluate inter-method, inter-observer, and
      intra-observer variability. Intra-observer error was greater for the microscopic
      method, although the error values are concomitant with experience. We found no
      statistically significant differences between the four methods examined, but
      certain caveats must be addressed when these methods are used.

PMID- 22621278
TI  - Nano-titanium dioxide modulates the dermal sensitization potency of DNCB.
AB  - We determined the ability of a model nanoparticle (NP) (titanium dioxide, TiO(2))
      to modulate sensitization induced by a known potent dermal sensitizer
      (dinitrochlorobenzene) using a variant of the local lymph node assay called lymph
      node proliferation assay.BALB/c mice received sub-cutaneous injections of vehicle
      (2.5 mM sodium citrate), TiO(2) NPs (0.004, 0.04 or 0.4 mg/ml) or pigment
      particles (0.04 mg/ml) both stabilized in sodium citrate buffer at the base of
      each ear (2x50MUl), before receiving dermal applications (on both ears) of 2,4
      Dinitrochlorobenzene (DNCB) (2x25MUl of 0.1%) or its vehicle (acetone olive oil -
      AOO (4:1)) on days 0, 1 and 2. On day 5, the stimulation index (SI) was
      calculated as a ratio of (3)HTdR incorporation in lymphocytes from DNBC-treated
      mice and AOO-treated controls. In a second experiment the EC(3)-value for DNCB (0
      to 0.1%) was assessed in the absence or presence of 0.04 mg/ml TiO(2). In a third
      experiment, the lymphocyte subpopulations and the cytokine secretion profile were
      analyzed after TiO(2) (0.04 mg/ml) and DNCB (0.1%) treatment. Injection of NPs in
      AOO-treated control mice did not have any effect on lymph node (LN)
      proliferation. DNCB sensitization resulted in LN proliferation, which was further
      increased by injection of TiO(2) NPs before DNCB sensitization. The EC(3) of
      DNCB, with prior injection of vehicle control was 0.041%, while injection with
      TiO(2) decreased the EC(3) of DNCB to 0.015%. TiO(2) NPs pre-treatment did not
      alter the lymphocyte subpopulations, but significantly increased the level of IL
      4 and decreased IL-10 production in DNCB treated animals.In conclusion, our study
      demonstrates that administration of nano-TiO(2) increases the dermal
      sensitization potency of DNCB, by augmenting a Th(2) response, showing the
      immunomodulatory abilities of NPs.

PMID- 22621279
TI  - Die and let live: harnessing BikDD to combat breast cancer stem cells.
AB  - One of the possible mechanisms contributing to the intrinsic resistance of cancer
      stem cells (CSCs) to conventional therapies is the inefficiency of activating the
      apoptotic machinery. In a recent study by Lang and colleagues, the engineered
      constitutively active pro-apoptotic protein BikDD, which works by inhibiting
      multiple Bcl-2 family members, was tested in various preclinical breast cancer
      models. Delivered to cells via an innovative cancer cell-specific gene-therapy
      approach, BikDD showed potent activity against CSCs and synergized with lapatinib
      and paclitaxel treatment. This novel and promising therapy warrants further
      translation to the clinic.

PMID- 22621283
TI  - Randomised trials in surgery: the burden of evidence.
AB  - A randomised controlled trial (RCT) is considered the hierarchical peak of
      evidence-based medicine and a general demand for any result to be evaluated by
      RCTs has evolved. Yet, many advances in operative surgery do not result from RCTs
      and many controversies remain without an RCT being conducted. A randomised
      comparison of laparoscopic versus open liver resection has recently been called
      for. Using such a trial and others as examples, we examine the limitations of
      randomised design in skill-dependant interventions. Surgical procedures are skill
      dependant, constantly developing, irreversible and traumatising. Additionally,
      placebo control is usually unethical and adequate blinding difficult or
      impossible to accomplish. Under these circumstances, surgeon and patient
      participation will be problematic and the resulting data will tend to have low
      external validity. While some of these obstacles can be modified, others will
      remain. Nonrandomised, prospective cohort comparison has other weaknesses, but
      may add complementary data with good external validity. An alternative hierarchy
      of evidence is warranted in this field.

PMID- 22621282
TI  - Effects of HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) on
      NEU/HER2 overexpressing mammary tumours in MMTV-NEU-NT mice monitored by Magnetic
      Resonance Spectroscopy.
AB  - BACKGROUND: The importance of ERBB2/NEU/HER2 in the response of breast tumours to
      the heat shock protein 90 (HSP90) inhibitor 17-allylamino-17
      demethoxygeldanamycin (17-AAG; tanespimycin) has been demonstrated in the clinic.
      ERBB2 is an oncoprotein client that is highly dependent on HSP90. This and other
      oncogenic client proteins (e.g. B-RAF, C-RAF, ALK and CDK4) are depleted by 17
      AAG in both animal tumours and patients. Here we investigate by Magnetic
      Resonance Spectroscopy (MRS) the metabolic response of 17-AAG in spontaneous,
      NEU/HER2 driven mammary tumours in transgenic MMTV-NEU-NT mice and in cells
      isolated and cultured from these tumours. METHODS: Mammary tumours were monitored
      by 31P MRS in vivo and in tumour extracts, comparing control and 17-AAG treated
      mice. A cell line derived from NEU/HER2 mammary tumours was also cultured and the
      effect of 17-AAG was measured by 31P MRS in cell extracts. Molecular biomarkers
      were assessed by immunoblotting in extracts from cells and tumours. For
      comparison of tumour volume, metabolite concentrations and Western blot band
      intensities, two-tailed unpaired t-tests were used. RESULTS: The NEU/HER2 mammary
      tumours were very sensitive to 17-AAG and responded in a dose-dependent manner to
      3 daily doses of 20, 40 and 80mg/kg of 17-AAG, all of which caused significant
      regression. At the higher doses, 31P MRS of tumour extracts showed significant
      decreases in phosphocholine (PC) and phosphoethanolamine (PE) whereas no
      significant changes were seen at the 20mg/kg dose. Extracts of isolated cells
      cultured from the mammary carcinomas showed a significant decrease in viable cell
      number and total PME after 17-AAG treatment. Western blots confirmed the expected
      action of 17-AAG in inducing HSP72 and significantly depleting HSP90 client
      proteins, including NEU/HER2 both in tumours and in isolated cells. CONCLUSIONS:
      The data demonstrate the high degree of sensitivity of this clinically relevant
      NEU/HER2-driven tumour model to HSP90 inhibition by 17-AAG, consistent with the
      clinical data, and suggest that the metabolic signature of choline phospholipids
      obtained by MRS could be useful both as a preclinical and clinical tool for
      investigating surrogate markers of response to treatment.

PMID- 22621284
TI  - Magnetooptical and structural investigations of five dimeric cobalt(II) complexes
      mimicking metalloenzyme active sites.
AB  - Four novel cobalt(II) complexes mimicking metalloenzyme active sites, novel
      C(14)H(22)Cl(12)Co(2)O(13).2C(3)H(8)O (1),
      C(28)H(36)Cl(24)Co(4)O(28).4C(4)H(8)O(2) (2),
      C(16)H(22)Cl(12)Co(2)O(13).C(2)HCl(3)O(2) (3), C(16)H(22)Cl(12)Co(2)O(13) (4),
      and one known C(40)H(78)Cl(8)Co(2)O(17) (5) are composed of the same core of two
      high-spin cobalt(II) centers triply bridged by water and two trichloroacetato (1
      4) or two pivalate (5) groups but differ in terminal ligands. The crystal
      structures of new compounds 1-4 belong to the space groups P 1, P2(1)/c, P 1, and
      Pbcn, respectively. All five investigated complexes contain Co atoms in distorted
      octahedral coordination. The complexes were characterized by magnetic
      susceptibility and magnetization measurements and by variable-temperature
      variable-field magnetic circular dichroism spectroscopy. Experimental data were
      analyzed in the frame of the theoretical model, which includes an unquenched
      orbital moment of the Co(II) ions. All investigated compounds are
      antiferromagnetically coupled with exchange constants in the range -1.5 to -2.1
      cm(-1). However, there is a significant difference between the crystal-field
      splitting parameters.

PMID- 22621285
TI  - Relationship between the neuroprotective effects of insulin-like growth factor-1
      and 17beta-oestradiol in human neuroblasts.
AB  - Insulin-like growth factor-1 (IGF-1) and oestrogens interact with each other as
      neuroprotective factors. We have previously demonstrated that 17beta-oestradiol
      protects against beta-amyloid and oxidative stress toxicity and increases the
      amount of cell cholesterol in human foetal neuroblasts (FNC). The present study
      aimed: (i) to assess the protective effects of IGF-1 in FNC cells; (ii) to
      investigate the relationship between IGF-1 and 17beta-oestradiol; and (iii) to
      determine whether cholesterol was a major mediator of the effects of IGF-1,
      similarly to 17beta-oestradiol. We found that IGF-1 effectively exerts
      neuroprotective effects in FNC cells. We also demonstrated that the IGF-1
      receptor (IGF-1R) pathway is needed to maintain oestrogen-mediated
      neuroprotection. Finally, we found that, opposite to 17beta-oestradiol, IGF-1 did
      not cause a significant increase in cell cholesterol. These findings indicate
      that a cross-talk between IGF-1 and 17beta-oestradiol occurs in FNC cells. In
      particular, the activation of the IGF-1R cascade appears to be fundamental to
      warrant 17beta-oestradiol-mediated neuroprotection, even though cell cholesterol
      does not play a major role as an effector of this pathway.

PMID- 22621286
TI  - Desolvation of BSA-ligand complexes measured using the quartz crystal
      microbalance and dual polarization interferometer.
AB  - By taking advantage of their unique difference in hydration sensitivity, we have
      shown that dual polarization interferometer (DPI) and quartz-crystal microbalance
      with dissipation monitoring (QCM-D) measurements can be used together to explore
      the degree of desolvation involved in the binding of small drug molecules to an
      immobilized bovine serum albumin film in real time. Results with DPI and QCM-D
      show significantly different mass values for three ligands of varying
      hydrophobicities that may be attributed to changes in the degree of hydration of
      the ligand-protein complexes in accordance with the physicochemical properties of
      the ligands. Furthermore, our data suggest that masses measured by QCM-D can be
      overwhelmed by changes in water content of ligand-protein, binary complexes,
      which has important consequences for future studies using mechanical resonators
      to study protein-binding events.

PMID- 22621288
TI  - Improving adherence to antiretroviral therapy in sub-Saharan African HIV-positive
      populations: an enhanced adherence package.
AB  - With the increasing access to antiretroviral therapy in sub-Saharan African HIV
      positive populations, it is important to find additional simple, effective, and
      feasible methods of improving and maintaining adequately high levels of
      adherence. In this study, we undertook the development, testing, implementation,
      and evaluation of various adherence support interventions at four sites in
      Uganda. A one-group pre- and post-intervention design was employed under routine
      operational conditions. Various adherence support strategies were identified,
      adapted, and developed. These strategies which included a combination of elements
      such as counseling, group education, leaflets, late attendee tracing, and
      adherence diaries was implemented for an antiretroviral treatment cohort which
      had baseline levels of adherence measured preintervention. Follow-up was from
      August 2009 through August 2010. Mean adherence and proportions of clients
      achieving adherence levels of 95% and above were determined at end of follow-up.
      Of the 967 participants enrolled, 856 (88.5%) completed follow-up. A before-and
      after comparison of outcomes demonstrated that mean adherence (95% confidence
      interval [CI]) improved statistically significant from baseline following
      implementation of the interventions (97.4% [96.9-97.9%] to 99.1% [99.0-99.3%],
      P=0.001). There was also a significant difference between proportions with
      optimal (>= 95%) and suboptimal adherence (<95%) pre- and post-intervention (7.0%
      difference, 95% CI: 4.6-9.4%, P<0.001). We conclude that additional adherence
      strategies (including counseling, group education, leaflets, late attendee
      tracing, and adherence diaries) can substantially improve and maintain high
      levels of treatment adherence in the long term. Health systems in sub-Saharan
      African countries should consider integrating these elements into their treatment
      programs for HIV/AIDS.

PMID- 22621289
TI  - Targeting the thyrotropin receptor in thyroid disease.
AB  - INTRODUCTION: The thyrotropin receptor (TSHR) is essential for thyroid growth and
      for the production of thyroid hormones. It is unique among the glycoprotein
      hormone receptors, in that some of the TSHRs undergo cleavage and shedding of the
      alpha subunit. AREAS COVERED: This review discusses the structure and function of
      the TSHR, followed by an evaluation of its role in thyroid disease. Possible
      limitations of the TSHR as a therapeutic target are also discussed. EXPERT
      OPINION: The TSHR is involved in a number of hereditary and acquired disorders of
      the thyroid making it of potential importance as a therapeutic target in thyroid
      disease. Expression of the TSHR in several non-thyroidal tissues and the
      development of systemic manifestations of thyroid disease suggest that the TSHR
      is also of interest as a therapeutic target outside the thyroid.

PMID- 22621290
TI  - Identification of perceived barriers of pain management in Iranian children: a
      qualitative study.
AB  - Hospitalized children are often inadequately treated for their pain. Paediatric
      nurses experience these inadequacies more than other health-care team members.
      This research was an attempt in the form of a phenomenological study to reveal
      some major barriers in children pain management as the nurses had perceived.
      Sixteen nurses were interviewed in the medical, surgical and infectious
      paediatric wards of a hospital in Iran. Data analysis were based on Colaizzi
      method that surfaced three main themes in different areas namely: organizational
      barriers, limitations relating to child's characteristics and barriers relating
      to the nature of disease and its treatments. The study results have shown
      organizational limitations added to the lack of authority for administering some
      medical intervention, inadequate equipment and utilities and unavailability of
      opioids as the main pain controlling and restricting factors. Additional factors
      that relate to the child specifications like age, temperament, behaviour,
      expression and gender affect the assessment and treatment of pain. The results
      revealed identified barriers in real context. It seems that some guidelines are
      needed to achieve optimal pain management.

PMID- 22621287
TI  - Evidence-based knee injections for the management of arthritis.
AB  - OBJECTIVE: Arthritis of the knee affects 46 million Americans. We aimed to
      determine the level of evidence of intraarticular knee injections in the
      management of arthritic knee pain. METHODS: We systematically searched
      PUBMED/MEDLINE and the Cochrane databases for articles published on knee
      injections and evaluated their level of evidence and recommendations according to
      established criteria. RESULTS: The evidence supports the use of intraarticular
      corticosteroid injections for rheumatoid arthritis (1A+ Level), osteoarthritis
      (1A+ Level), and juvenile idiopathic arthritis (2C+ Level). Pain relief and
      functional improvement are significant for months up to 1 year after the
      injection. Triamcinolone hexacetonide offers an advantage over triamcinolone
      acetonide and should be the intraarticular steroid of choice (2B+ Level).
      Intraarticular injection of hyaluronate may provide longer pain relief than
      steroid injection in osteoarthritis (2B+ Level). It can also be effective for
      rheumatoid arthritis knee pain (1A+ Level). However, it is only recommended for
      patients with significant surgical risk factors and for patients with mild
      radiographic disease in whom conservative treatment has failed (2B+/- Level).
      Botulinum toxin type A injection is effective in reducing arthritic knee pain
      (2B+ Level), and so is tropisetron (2B+ Level) and tanezumab (2B+ Level). The new
      agents, such as rAAV2-TNFR:Fc, SB-210396/CE 9.1, and various radioisotopes have
      provided various degrees of success, but their long-term safety and efficacy
      remains to be determined. CONCLUSIONS: We conclude that strong evidence supports
      the use of intraarticular knee injection as a valuable intervention in the
      continuum of management of arthritis between conservative treatment and knee
      surgeries.

PMID- 22621291
TI  - Victorian rural emergency care--a case for advancing nursing practice.
AB  - The aim of this paper is to profile the emergency care patients seen by a
      selection of rural health services in Victoria, and show how advancing nursing
      practice could contribute to a more sustainable model of care. Quantitative
      patient data extracted from five rural health services across Victoria ranging in
      size, were analysed using descriptive statistic techniques. Most patients who
      attended for emergency care did not require urgent or immediate medical attention
      (70%), many had minor injuries (over 30%) and did not need medicines (57%) but
      were attended by a doctor either directly or via telephone (over 74%). If
      emergency care services in rural Victoria are to be sustained in the face of
      severe medical workforce shortages, registered nurses will need to be enabled
      through professional development, legislation and organisation policy to manage
      autonomously a larger proportion of the non-urgent, less complex patients who
      present to these emergency services.

PMID- 22621292
TI  - Care plans using concept maps and their effects on the critical thinking
      dispositions of nursing students.
AB  - It is expected that nursing education improves abilities of students in solving
      problems, decision making and critical thinking in different circumstances. This
      study was performed to analyse the effects of care plans prepared using concept
      maps on the critical thinking dispositions of students. An experimental group and
      a control group were made up of a total of 80 freshman and sophomore students
      from the nursing department of a health school. The study used a pre-test post
      test control group design. The critical thinking dispositions of the groups were
      measured using the California Critical Thinking Disposition Inventory. In
      addition, the care plans prepared by the experimental group students were
      evaluated using the criteria for evaluating care plans with concept maps. T-test
      was used in analysing the data. The results showed that there were no
      statistically significant differences in the total and sub-scale pre-test scores
      between the experimental group and control group students. There were also
      significant differences in the total and sub-scale post-test scores between the
      experimental group and control group students. There were significant differences
      between concept map care plan evaluation criteria mean scores of the experimental
      students. In the light of these findings, it could be argued that the concept
      mapping strategy improves critical thinking skills of students.

PMID- 22621293
TI  - Dancing with data: an example of acquiring theoretical sensitivity in a grounded
      theory study.
AB  - Glaser suggested that the conceptual route from data collection to a grounded
      theory is a set of double back steps. The route forward inevitably results in the
      analyst stepping back. Additionally sidestepping through, leading participants
      down lines of inquiry and following data threads with other participants, is also
      characteristic of acquiring theoretical sensitivity, a key concept in grounded
      theory. Other ways of acquiring theoretical sensitivity comprise: reading the
      literature, open coding, category building, reflecting in memos followed by
      doubling back on data collection once further lines of inquiry are opened up.
      This paper describes how we 'danced with data' in pursuit of heightened
      theoretical sensitivity in a grounded theory study of information use by nurses
      working in general practice in New Zealand. Providing an example of how
      analytical tools are employed to theoretically sample emerging concepts.

PMID- 22621294
TI  - Levels of empathy in undergraduate nursing students.
AB  - Empathy and absence of prejudice and stigma are instrumental in facilitating
      effective nurse-patient relations. This study assessed empathy levels and regard
      for specific medical conditions in undergraduate nursing students. A cross
      sectional study was undertaken using paper-based versions of the Jefferson Scale
      of Physician Empathy (JSPE) and Medical Condition Regard Scale (MCRS), along with
      a brief set of demographic questions. Participants reported good empathy levels
      on JSPE. Attitudes towards intellectual disability, chronic pain, acute mental
      illness and terminal illness rated well on MCRS. Attitudes towards substance
      abuse, however, were lower. There were no significant differences between age
      groups, gender or year level of study. Overall results of this study were
      positive. Nursing students demonstrated acceptable empathy levels. Attitudes
      towards patients who abuse substances highlight an area that needs both further
      exploration and addressing. Attitudes towards mental health diagnoses were
      particularly favourable given that these often attract stigma and negative
      attitudes.

PMID- 22621295
TI  - Exploring the meaning of hypoglycaemia to community-dwelling Singaporean Chinese
      adults living with type 2 diabetes mellitus.
AB  - This study aimed to explore how community-dwelling Singaporean Chinese adults
      diagnosed with type 2 diabetes mellitus experience hypoglycaemia. A qualitative
      interpretive research design was employed. Semi-structured interviews were
      conducted with six participants from a Singaporean diabetes specialist outpatient
      clinic, transcribed verbatim and analysed using qualitative manual thematic
      analysis. Eight major themes emerged: experiencing symptoms, knowing
      hypoglycaemia is manageable, using acute measures, using preventative strategies;
      applying knowledge, identifying causes of hypoglycaemia, forming relationships
      and working with health-care professionals. Participants underestimated the
      impact of hypoglycaemia mainly due to their experiencing mild and infrequent
      episodes, and knowledge deficits. Health-care professionals' roles were limited
      to information providers, and they were perceived as detached and impersonal.
      Theimplications are that health-care professionals need to provide more client
      focused education, and improve the quality of their interpersonal relationships
      to ensure shared decision-making with their clients.

PMID- 22621296
TI  - Influence of Type D personality on health-related quality of life among Korean
      patients with end-stage renal disease.
AB  - The purposes of this study were to explore the prevalence of Type D personality
      and the impact of Type D personality (the combination of negative affectivity and
      social inhibition) on health-related quality of life (HRQOL) in end-stage renal
      disease (ESRD) patients and to determine whether this link of Type D personality
      to HRQOL is mediated by depressive symptoms. Patients (n = 144) from an
      outpatient nephrology clinic of a university hospital participated in this cross
      sectional study. The prevalence of Type D personality using Type D Personality
      Scale-14 was 26%. After adjustment for patients' characteristics and depressive
      symptoms in multivariate analysis, Type D personality was an independent
      predictor of HRQOL. This relation of Type D personality to HRQOL was mediated by
      depressive symptoms. Our findings underline that intervention should be directed
      towards reducing depressive symptoms in patients with Type D personality in order
      to improve HRQOL of ESRD patients.

PMID- 22621297
TI  - Health-promoting lifestyle and depression in metabolic syndrome patients in
      Korea.
AB  - This cross-sectional study assessed the association between health-promoting
      lifestyle and depression in metabolic syndrome patients by using a questionnaire
      survey in Korea. Data were collected from 195 adults (> 20 years old) with
      hypertension, dyslipidemia and diabetes. The correlation coefficient (r) between
      health-promoting lifestyle and depression was -0.309 (P < 0.001), and correlation
      between individual lifestyle dimensions and depression varied from -0.135 to 
      0.391. The non-depressed group had higher health-promoting lifestyle scores than
      the depressed group (P = 0.003). Scores for three dimensions of the health
      promoting lifestyle profile--self-actualization (P < 0.001), interpersonal
      support (P = 0.001) and stress management (P = 0.025)--were significantly higher
      in the non-depressed groups. Logistic regression analysis provided an odds ratio
      of 2.766 (P = 0.003) for health-promoting lifestyle between the two groups. For
      patients with metabolic syndrome, depression was negatively associated with
      health-promoting lifestyle and is an important factor affecting health-promoting
      behaviour.

PMID- 22621298
TI  - Assessing undergraduate nursing and midwifery students' compliance with hand
      hygiene by self-report.
AB  - The aim of the study was to assess undergraduate nursing and midwifery students'
      hand hygiene (HH) compliance. The questionnaire included questions about HH
      behaviours and compliance during patient care, and Fulkerson scale was used to
      relate HH to cleanliness of various activities. 57.4% of them reported that they
      used liquid soap for HH. 18.6% of them did not dry their hands after washing.
      65.9% of them said that they performed HH when passing from one patient to
      another. HH rates were 80.7% after removing gloves. The first six activities on
      the Fulkerson scale were described as 'clean'; most of the students assessed the
      third, fourth, fifth and sixth activities as 'dirty'. Compliance with HH was high
      for all dirty and clean activities. Self-report method indicates compliance with
      HH which was an easy and inexpensive way to provide the information on HH.

PMID- 22621299
TI  - The effect psychoeducation intervention has on the caregiving burden of
      caregivers for schizophrenic patients in Turkey.
AB  - This study was conducted to determine the effects psychoeducation given to
      caregivers of schizophrenic patients has on the level of care burdens. The model
      used was one group pre-test post-test pre-experimental model. It was conducted on
      31 caregivers in psychiatry clinics between October 2007 and June 2008. Data were
      collected using the 'Zarit Caregiver Burden Scale' and the questionnaire form
      that determined the introductory features of caregivers. The study group
      participated in eight psychoeducation sessions. The average pre-test score of
      care burden for caregivers was 57.2 +/- 9.9, and the average post-test score was
      34.3 +/- 9.9. The distinction between the average pre-test and post-test score of
      care burden for caregivers was significant (P = 0.001). Psychoeducation, given
      for caregivers of patients with schizophrenia, had a significant effect in
      decreasing individuals' caregiving burdens. Psychoeducation programmes directed
      at families should be considered as a therapeutic strategy for patients with
      schizophrenia.

PMID- 22621300
TI  - A structured telephonic counselling to promote the exclusive breastfeeding of
      healthy babies aged zero to six months: a pilot study.
AB  - This pilot study aimed to test the effectiveness of a structured telephonic
      counselling (STC) on exclusive breastfeeding (EB) on healthy babies. The study
      was carried out on 114 primiparous women from February to March 2009. After
      randomization, women were divided into two groups: 55 receiving STC and 59
      receiving conventional counselling. At 1, 3 and 5 months after delivery, a nurse
      specialist evaluated the EB rates, the influence of mother's educational level
      and employment status on EB. Breastfeeding rates in STC were higher compared to
      conventional counselling (P < 0.01); resuming work was not an EB discouraging
      variable as 74.5% women in the STC resumed work vs. 54.2% of the conventional
      counselling. Breastfeeding promotion should start during pregnancy, advising
      women about benefits for the child in receiving human milk. STC should be used to
      improve EB in primiparous women.

PMID- 22621301
TI  - Non-infectious hyperthermia in acute brain injury patients: relationships to
      mortality, blood pressure, intracranial pressure and cerebral perfusion pressure.
AB  - The present study was conducted to investigate the frequency of hyperthermia
      during the first 72 h after acute brain injury, and to compare subjects that
      developed hyperthermia with those that did not with respect to blood pressure,
      intracranial pressure (ICP), cerebral perfusion pressure (CPP), Glasgow Coma
      Scale (GCS) score and mortality. This study was conducted by performing a
      retrospective medical record review of 126 brain injury patients admitted to the
      neurological intensive care unit of a university hospital located in Incheon,
      South Korea. Our results showed that 25.4% of the subjects had hyperthermia for
      at least 1 day during the first 3 days of hospitalization. Hyperthermic subjects
      demonstrated higher mortality and ICP, and lower CPP and GCS scores than non
      hyperthermic subjects, indicating a reduced cerebral blood flow. The findings may
      provide a possible explanation for poor clinical outcome and offer justification
      for the careful monitoring of body temperature in patients with acute brain
      injury.

PMID- 22621302
TI  - Australian registered and enrolled nurses: is there a difference?
AB  - There are two categories of nurse registered to practise in Australia, the degree
      educated registered nurse and the certificate/diploma trained enrolled nurse
      (EN). While it is argued that the roles of the two categories of nurse in
      Australia are different, recent changes to the educational preparation and
      supervision requirements of ENs have narrowed these differences. This paper
      examines the existing literature to determine the perceived differences and
      similarities between registered and ENs in Australia. Differences identified
      included registration requirements, educational preparation, supervisory
      requirements and role expectation. Further research needs to be undertaken to
      examine the educational preparation of registered and ENs in order to obtain a
      greater understanding of role expectations on graduation. Supervision processes
      also require reviewing to demonstrate differences between indirect supervision
      and independent practice for ENs.

PMID- 22621303
TI  - Attitudes and practices of school-aged girls towards menstruation.
AB  - The purpose of this study was to (i) investigate attitude and menstruation
      related practices in Jordanian school-aged girls; (ii) identify the influence of
      premenstrual preparation on girls' attitude and menstruation-related practices. A
      descriptive cross-sectional design was used. Data was collected from a
      convenience sample of 490 school-age girls (12-18 years) from different districts
      in Jordan. Self-report instruments [Menstrual Attitude Questionnaire (MAQ), and
      Menstrual Practices Questionnaires (MPQ)] were used to assess the study
      variables. Descriptive statistics, correlation and chi-square tests were used to
      analyze the data. It was found that menstrual attitude and practices were
      positively correlated. Poor attitude toward menstruation and low menstrual
      practices were significantly associated with inadequate premenstrual preparation.
      There is a need to prepare girls for menstruation before menarche. The role of
      the schools and teachers should be reinforced through formal and well planned
      reproductive health educators for girls and their mothers.

PMID- 22621304
TI  - Reflectance confocal microscopy for quantification of Sarcoptes scabiei in
      Norwegian scabies.
AB  - BACKGROUND AND OBJECTIVES: In vivo reflectance-mode confocal microscopy (RCM) can
      be used for the diagnosis of scabies. This study quantifies S. scabiei and its
      eggs and droppings in a patient affected by Norwegian Scabies (NS), and describes
      their distribution within the epidermis and in different body areas. METHODS:
      Different skin sites were randomly chosen in four sections (head, upper limbs,
      trunk and inferior limbs) of the body surface area (BSA) to acquire a total of 60
      RCM z-stacks. The number of mites and eggs, the presence of droppings, as well as
      the minimum epidermal depth at which mites, eggs and faeces were detectable, was
      established for each z-stack. The total number of mites and eggs on the entire
      BSA was calculated considering the weighted mean for the four sections of the
      BSA. RESULTS: A total of 15.8 millions of S. scabiei and 7.2 millions of eggs
      were calculated. Mites, eggs and faeces were homogeneously distributed all over
      the body surface. Droppings, easily recognized by the RCM, were present in more
      than an half of the analyzed cutaneous sites and were associated with the
      presence of parasites (chi-squared test, P = 0.002). CONCLUSIONS: Our study
      illustrates the ability of RCM to identify, locate, and quantify the various
      forms of S. scabiei in human skin. NS is an extremely contagious disease,
      considering that the number of mites can be around 15.8 millions. Moreover, all
      areas of the body are parasitized in NS, including the face.

PMID- 22621305
TI  - Negotiating uncertain terrain: a qualitative analysis of clinicians' experiences
      of refractory suffering.
AB  - In palliative care, the witnessing of unrelieved (refractory) suffering takes its
      toll on all concerned; however, the effect on experienced palliative clinicians
      of witnessing such suffering has largely been unexplored. The aim of this study
      was to examine health care professionals' (nurses, doctors, and allied health
      workers) experiences of working with a patient's refractory suffering, together
      with their clinical management strategies. A qualitative research design
      involving semistructured interviews and an online questionnaire was used to
      collect the data. Seventeen experienced palliative care clinicians participated;
      13 with face-to-face interviews and a further 4 by an online questionnaire. The
      overarching theme of negotiating uncertain terrain was common across all
      clinician narratives. In order for them to work successfully with a patient's
      refractory suffering, the clinicians had to negotiate areas of practice
      characterized by uncertainty, with no clear directions and with few expert
      guides. In reviewing their experiences, they identified within an overarching
      theme of negotiating uncertain terrain four subthemes: Changing Approach from
      "Fixing" to "Being With," Maintaining Perspective, Negotiating and Maintaining
      Boundaries, and Living the Paradoxes. This study highlights that dealing with
      patients' refractory suffering involves clinicians moving into uncertain and
      unexplored territory. For them to work effectively in this terrain the clinicians
      need wisdom, courage, and a commitment to journeying alongside the suffering
      person.

PMID- 22621306
TI  - Implications of constructed biologic subtype and its relationship to locoregional
      recurrence following mastectomy.
AB  - INTRODUCTION: We examined the prognostic value of biologic subtype on
      locoregional recurrence (LRR) after mastectomy in a cohort of low risk women who
      did not receive adjuvant radiation therapy. METHODS: A total of 819 patients with
      invasive breast cancer underwent mastectomy from January 2000 through December
      2005. No patient received preoperative chemotherapy. Estrogen receptor (ER)
      receptor, progesterone receptor (PR) and human epidermal growth factor receptor 2
      (HER2) status were used to construct the following 4 subtypes: i) ER+ or PR+ and
      HER2- (HR+/HER2-), ii) ER+ or PR+ and HER2+ (HR+/HER2+), iii) ER- and PR- and
      HER2+ (HR-/HER2+)and iv) ER- and PR- and HER2- (HR-/HER2-). LRR-free survival was
      estimated by the Kaplan-Meier method. Cox proportional hazard models were used to
      evaluate the association between time-to-event outcomes and patient prognostic
      factors. RESULTS: At a median follow-up of 58 months, five-year cumulative
      incidence of LRR for the entire cohort was 2.5%. Subtype specific LRR rates were
      1% for HR+/HER2-, 6.5% in HR+/HER2+, 2% for HR-/HER2+ and 10.9% for HR-/HER2- (P
      < 0.01). In HER-2+ patients (irrespective of ER/PR status), trastuzumab therapy
      was not associated with LRR-free survival. On multivariate analysis, one to three
      positive lymph nodes (HR 4.75 (confidence interval (CI) 1.75 to 12.88, P < 0.01),
      >= 4 positive lymph nodes (HR23.4 (CI 4.64 to 117.94, P < 0.01), HR+/HER2+ (HR
      4.26 (CI 1.05 to 17.33), P = 0.04), and HR-/HER2- phenotype (HR 13.87 (CI 4.96 to
      38.80), P < 0.01) were associated with shorter LRR-free survival whereas age > 50
      at diagnosis (HR 0.31 (CI 0.12 to 0.80), P = 0.02) was associated with improved
      LRR-free survival. Among the HR-/HER2- subtypes, five-year LRR incidence was
      23.4% in patients with positive lymph nodes compared to 7.8% for lymph node
      negative patients (P = 0.01), although this association did not reach
      significance when the analysis was limited to HR-/HER2- women with only one to
      three positive lymph nodes (15.6% versus 7.8%, P = 0.11). CONCLUSIONS:
      Constructed subtype is a prognostic factor for LRR after mastectomy among low
      risk women not receiving adjuvant radiation therapy, although rates of LRR remain
      low across subtypes. Patients with node positive, HR-/HER2- type tumors were more
      likely to experience LRR following mastectomy alone. Prospective studies to
      further investigate the potential benefit of adjuvant radiation therapy in these
      women are warranted.

PMID- 22621307
TI  - Effects of enzymatic activation on the distribution of fluorescently tagged MMP-2
      cleavable peptides in cancer cells and spheroids.
AB  - A peptide tagged at the N-terminus with FITC, at the C-terminus with coumarin
      343, and incorporating a sequence selectively cleaved by the matrix
      metalloproteinase, MMP-2, was synthesized to investigate the effect of peptide
      cleavage on both cellular accumulation and distribution in cancer cell spheroids.
      The peptide was shown by HPLC and mass spectroscopy to be cleaved in the presence
      of MMP-2 at the expected site. The cellular and spheroid distribution of each of
      the fragments was monitored using confocal fluorescence microscopy. The intact
      peptide had minimal accumulation in 2D-cultured DLD-1 cells that do not express
      MMP-2 in these conditions. Following addition of serum containing MMP-2 to the
      cell media, the cleaved C-terminal fragment was seen to enter the cells, while
      the N-terminal fragment remained extracellular, evidently blocked by the presence
      of the FITC group. 3D culture of DLD-1 cells as spheroids resulted in measurable
      MMP-2 activity. Different distribution patterns of the two fluorophores were seen
      in spheroids treated with the intact peptide, consistent with cleavage occurring.
      Different rates of accumulation of each of the fragments were observed within the
      spheroid over time, which is attributed to the extent of accumulation and
      sequestration of the fragments by cells residing in the periphery of the
      spheroids. The outcomes suggest that tumor-associated enzymes have the potential
      to modify the distribution of peptides and peptide fragments in solid tumors by
      modifying the cellular uptake of those peptides. 

PMID- 22621308
TI  - Towards the identification of protein complexes and functional modules by
      integrating PPI network and gene expression data.
AB  - BACKGROUND: Identification of protein complexes and functional modules from
      protein-protein interaction (PPI) networks is crucial to understanding the
      principles of cellular organization and predicting protein functions. In the past
      few years, many computational methods have been proposed. However, most of them
      considered the PPI networks as static graphs and overlooked the dynamics inherent
      within these networks. Moreover, few of them can distinguish between protein
      complexes and functional modules. RESULTS: In this paper, a new framework is
      proposed to distinguish between protein complexes and functional modules by
      integrating gene expression data into protein-protein interaction (PPI) data. A
      series of time-sequenced subnetworks (TSNs) is constructed according to the time
      that the interactions were activated. The algorithm TSN-PCD was then developed to
      identify protein complexes from these TSNs. As protein complexes are
      significantly related to functional modules, a new algorithm DFM-CIN is proposed
      to discover functional modules based on the identified complexes. The
      experimental results show that the combination of temporal gene expression data
      with PPI data contributes to identifying protein complexes more precisely. A
      quantitative comparison based on f-measure reveals that our algorithm TSN-PCD
      outperforms the other previous protein complex discovery algorithms. Furthermore,
      we evaluate the identified functional modules by using "Biological Process"
      annotated in GO (Gene Ontology). The validation shows that the identified
      functional modules are statistically significant in terms of "Biological
      Process". More importantly, the relationship between protein complexes and
      functional modules are studied. CONCLUSIONS: The proposed framework based on the
      integration of PPI data and gene expression data makes it possible to identify
      protein complexes and functional modules more effectively. Moveover, the proposed
      new framework and algorithms can distinguish between protein complexes and
      functional modules. Our findings suggest that functional modules are closely
      related to protein complexes and a functional module may consist of one or
      multiple protein complexes. The program is available at
      http://netlab.csu.edu.cn/bioinfomatics/limin/DFM-CIN/index.html.

PMID- 22621309
TI  - Highly enantio- and diastereoselective vinylogous aldol reaction by LiCl-assisted
      BINOL-titanium species.
AB  - The first highly enantio- and diastereoselective vinylogous aldol reaction
      between propionyl acetate-derived Brassard's diene and aldehydes was accomplished
      by titanium-lithium combined Lewis acid, affording delta-hydroxy-gamma-methyl
      beta-methoxy acrylates. This methodology was utilized in convenient and concise
      construction of the polypropionate moiety in cystothiazole A and melithiazole C.

PMID- 22621310
TI  - Internal morphological analysis for age estimation of blow fly pupae (Diptera:
      Calliphoridae) in postmortem interval estimation.
AB  - Larvae and pupae of blow fly species are frequently used in postmortem interval
      estimation, their age indicating minimum time since death. Most studies have
      considered age estimation of larvae, neglecting study of pupae. Relative
      development of external pupal features is useful, but there are also internal
      changes during metamorphosis that may be indicators of age, utilizing
      histological techniques. This study aimed to optimize preservation and
      histological analysis of blow fly pupae, specifically Calliphora vicina Robineau
      Desvoidy and Lucilia sericata (Meigen), and to examine internal features with
      potential for age estimation. Effect of hot-water-killing and different
      preservatives were examined. It was determined that blow fly pupae should be
      pierced through the three tagma, hot-water-killed, and preserved in 80% ethanol
      as the optimal preservation for subsequent analyses. Hematoxylin and eosin
      stained pupal sections revealed differences in brain and thoracic muscle
      development throughout the pupal stage with potential for age estimation.

PMID- 22621311
TI  - Pulmonary exposure to single-walled carbon nanotubes does not affect the early
      immune response against Toxoplasma gondii.
AB  - BACKGROUND: Single-walled carbon nanotubes (SWCNT) trigger pronounced
      inflammation and fibrosis in the lungs of mice following administration via
      pharyngeal aspiration or inhalation. Human exposure to SWCNT in an occupational
      setting may occur in conjunction with infections and this could yield enhanced or
      suppressed responses to the offending agent. Here, we studied whether the
      sequential exposure to SWCNT via pharyngeal aspiration and infection of mice with
      the ubiquitous intracellular parasite Toxoplasma gondii would impact on the
      immune response of the host against the parasite. METHODS: C57BL/6 mice were pre
      exposed by pharyngeal administration of SWCNT (80 + 80 MUg/mouse) for two
      consecutive days followed by intravenous injection with either 1x103 or 1x104
      green fluorescence protein and luciferase-expressing T. gondii tachyzoites. The
      dissemination of T. gondii was monitored by in vivo bioluminescence imaging in
      real time for 7 days and by plaque formation. The inflammatory response was
      analysed in bronchoalveolar lavage (BAL) fluid, and by assessment of
      morphological changes and immune responses in lung and spleen. RESULTS: There
      were no differences in parasite distribution between mice only inoculated with T.
      gondii or those mice pre-exposed for 2 days to SWCNT before parasite inoculum.
      Lung and spleen histology and inflammation markers in BAL fluid reflected the
      effects of SWCNT exposure and T. gondii injection, respectively. We also noted
      that CD11c positive dendritic cells but not F4/80 positive macrophages retained
      SWCNT in the lungs 9 days after pharyngeal aspiration. However, co-localization
      of T. gondii with CD11c or F4/80 positive cells could not be observed in lungs or
      spleen. Pre-exposure to SWCNT did not affect the splenocyte response to T.
      gondii. CONCLUSIONS: Taken together, our data indicate that pre-exposure to SWCNT
      does not enhance or suppress the early immune response to T. gondii in mice.

PMID- 22621312
TI  - Diagnostic and treatment delay among Tuberculosis patients in Afar Region,
      Ethiopia: a cross-sectional study.
AB  - BACKGROUND: TB is a major public health problem globally and Ethiopia is 8th
      among the 22 high burden countries. Early detection and effective treatment are
      pre-requisites for a successful TB control programme. In this regard, early
      health seeking action from patients' side and prompt diagnosis as well as
      initiation of treatment from the health system's side are essential steps. The
      aim of this study was to assess delay in the diagnosis and treatment of TB in a
      predominantly pastoralist area in Ethiopia. METHODS: On a cross-sectional study,
      two hundred sixteen TB patients who visited DOTS clinics of two health facilities
      in Afar Region were included consecutively. Time from onset of symptoms till
      first consultation of formal health providers (patients' delay) and time from
      first consultation till initiation of treatment (health system's delay) were
      analyzed. RESULTS: The median patients' and health system's delay were 20 and
      33.5 days, respectively. The median total delay was 70.5 days with a median
      treatment delay of 1 day. On multivariate logistic regression, self-treatment
      (aOR. 3.99, CI 1.50-10.59) and first visit to non-formal health providers (aOR.
      6.18, CI 1.84-20.76) were observed to be independent predictors of patients'
      delay. On the other hand, having extra-pulmonary TB (aOR. 2.08, CI 1.08- 4.04),
      and a first visit to health posts/clinics (aOR. 19.70, CI 6.18-62.79), health
      centres (aOR. 4.83, CI 2.23-10.43) and private health facilities (aOR. 2.49, CI
      1.07-5.84) were found to be independent predictors of health system's delay.
      CONCLUSIONS: There is a long delay in the diagnosis and initiation of treatment
      and this was mainly attributable to the health system. Health system
      strengthening towards improved diagnosis of TB could reduce the long health
      system's delay in the management of TB in the study area.

PMID- 22621313
TI  - A model of school problems, academic failure, alcohol initiation, and the
      relationship to adult heroin injection.
AB  - The current study uses structural equation modeling to investigate factors
      associated with alcohol initiation and injection heroin use. Baseline data from
      the NEURO-HIV Epidemiologic Study in Baltimore, Maryland, were used. Participants
      were 404 injection heroin users (M(age) = 32.72) with a history of regular
      injection in their lifetime. Latent variables were created for self-reported
      school problems and academic failure. The final model indicated that greater
      school problems were associated with earlier alcohol initiation (beta = -0.22, p
      < .001) and earlier alcohol initiation was associated with greater frequency of
      recent heroin use (beta = -0.12, p < .05). Academic failure was directly related
      to greater frequency of recent heroin injection (beta = 0.15, p < .01). The
      results expand research investigating the relationship between adolescent
      behavior and illicit drug use in adulthood.

PMID- 22621315
TI  - Substrate-dependent divergent outcomes from catalytic reactions of silyl
      protected enol diazoacetates with nitrile oxides: azabicyclo[3.1.0]hexanes or 5
      arylaminofuran-2(3H)-ones.
AB  - Dirhodium(II)-catalyzed reactions of silyl-protected enol diazoacetates with
      nitrile oxides exhibit high nitrile oxide substituent dependence in the
      production rearrangement products via dipolar cycloaddition and either the Neber
      rearrangement or the Lossen rearrangement.

PMID- 22621316
TI  - Efficacy, safety and tolerability of ongoing statin plus ezetimibe versus
      doubling the ongoing statin dose in hypercholesterolemic Taiwanese patients: an
      open-label, randomized clinical trial.
AB  - BACKGROUND: Reducing low-density lipoprotein cholesterol (LDL-C) is associated
      with reduced risk for major coronary events. Despite statin efficacy, a
      considerable proportion of statin-treated hypercholesterolemic patients fail to
      reach therapeutic LDL-C targets as defined by guidelines. This study compared the
      efficacy of ezetimibe added to ongoing statins with doubling the dose of ongoing
      statin in a population of Taiwanese patients with hypercholesterolemia. METHODS:
      This was a randomized, open-label, parallel-group comparison study of ezetimibe
      10 mg added to ongoing statin compared with doubling the dose of ongoing statin.
      Adult Taiwanese hypercholesterolemic patients not at optimal LDL-C levels with
      previous statin treatment were randomized (N = 83) to ongoing statin + ezetimibe
      (simvastatin, atorvastatin or pravastatin + ezetimibe at doses of 20/10, 10/10 or
      20/10 mg) or doubling the dose of ongoing statin (simvastatin 40 mg, atorvastatin
      20 mg or pravastatin 40 mg) for 8 weeks. Percent change in total cholesterol, LDL
      C, high-density lipoprotein cholesterol (HDL-C) and triglycerides, and specified
      safety parameters were assessed at 4 and 8 weeks. RESULTS: At 8 weeks, patients
      treated with statin + ezetimibe experienced significantly greater reductions
      compared with doubling the statin dose in LDL-C (26.2% vs 17.9%, p = 0.0026) and
      total cholesterol (20.8% vs 12.2%, p = 0.0003). Percentage of patients achieving
      treatment goal was greater for statin + ezetimibe (58.6%) vs doubling statin
      (41.2%), but the difference was not statistically significant (p = 0.1675). The
      safety and tolerability profiles were similar between treatments. CONCLUSION:
      Ezetimibe added to ongoing statin therapy resulted in significantly greater lipid
      lowering compared with doubling the dose of statin in Taiwanese patients with
      hypercholesterolemia. Studies to assess clinical outcome benefit are ongoing.
      TRIAL REGISTRATION: Registered at ClinicalTrials.gov: NCT00652327.

PMID- 22621317
TI  - No relationship between fear of childbirth and pregnancy-/delivery-outcome in a
      low-risk Dutch pregnancy cohort delivering at home or in hospital.
AB  - OBJECTIVE: To examine the relationship of fear of childbirth (FOC), general
      anxiety and depression during pregnancy and postpartum with birth complications.
      METHODS: For this prospective cohort study 105 healthy women with low-risk
      pregnancies (until at least 30 weeks gestation) completed the Wijma Delivery
      Expectancy/Experience Questionnaire (W-DEQ) and the Hospital Anxiety and
      Depression Scale (HADS) at 30 weeks gestation and 6 weeks postpartum. These
      results were related with delivery characteristics. RESULTS: FOC during pregnancy
      was not related to complications during labour and delivery. In a regression
      analysis, both multiparity and medical interventions were predictors for higher
      postpartum FOC. A positive correlation was found between FOC during pregnancy and
      FOC at six weeks postpartum, corrected for complications during childbirth (r =
      0.45, p < 0.001). CONCLUSIONS: The birth giving process was not related to FOC
      during pregnancy, but the pre-partum level of FOC certainly is predictive of the
      level of postpartum FOC, suggesting that FOC as measured during gestation may
      influence the interpretation of the birth experience itself. We did find a
      positive relationship between both parity and medical interventions during
      childbirth and FOC postpartum.

PMID- 22621318
TI  - The publication of Diabetes UK position statements and care recommendations; a
      virtual issue.
AB  - Diabetes UK is the charity that cares for, connects with and campaigns on behalf
      of all people affected by and at risk of diabetes. Founded in 1934 by the
      novelist H. G. Wells and Dr R. D. Lawrence, the charity has always combined the
      expertise of lay and professional members to achieve its mission to improve the
      lives of people with diabetes and to work towards a future without diabetes.

PMID- 22621314
TI  - Generation of DNA-damaging reactive oxygen species via the autoxidation of
      hydrogen sulfide under physiologically relevant conditions: chemistry relevant to
      both the genotoxic and cell signaling properties of H(2)S.
AB  - Hydrogen sulfide (H(2)S) has long been known for its toxic properties; however,
      in recent years, evidence has emerged that this small, gaseous molecule may serve
      as an endogenous cell-signaling agent. Though perhaps surprising in light of its
      potential role as an endogenous signaling agent, a number of studies have
      provided evidence that H(2)S is a DNA-damaging mutagen. In the work reported
      here, the chemical mechanisms of DNA damage by H(2)S were examined. Using a
      plasmid-based DNA strand cleavage assay, we found that micromolar concentrations
      of H(2)S generated single-strand DNA cleavage. Mechanistic studies indicate that
      this process involved autoxidation of H(2)S to generate superoxide, hydrogen
      peroxide, and, ultimately, the well-known DNA-damaging agent hydroxyl radical via
      a trace metal-mediated Fenton-type reaction. Strand cleavage by H(2)S proceeded
      in the presence of physiological thiol concentrations, and the known byproducts
      of H(2)S oxidation such as thiosulfate, sulfite, and sulfate do not contribute to
      the strand cleavage process. However, initially generated oxidation products such
      as persulfide (S(2)(2-)) likely undergo rapid autoxidation reactions that
      contribute to the generation of superoxide. The potential relevance of
      autoxidation processes to the genotoxic and cell signaling properties of H(2)S is
      discussed.

PMID- 22621319
TI  - Photoinduced electron transfer in linear triarylamine-photosensitizer
      anthraquinone triads with ruthenium(II), osmium(II), and iridium(III).
AB  - A rigid rod-like organic molecular ensemble comprised of a triarylamine electron
      donor, a 2,2'-bipyridine (bpy) ligand, and a 9,10-anthraquinone acceptor was
      synthesized and reacted with suitable metal precursors to yield triads with
      Ru(bpy)(3)(2+), Os(bpy)(3)(2+), and [Ir(2-(p-tolyl)pyridine)(2)(bpy)](+)
      photosensitizers. Photoexcitation of these triads leads to long-lived charge
      separated states (tau = 80-1300 ns) containing a triarylamine cation and an
      anthraquinone anion, as observed by transient absorption spectroscopy. From a
      combined electrochemical and optical spectroscopic study, the thermodynamics and
      kinetics for the individual photoinduced charge-separation and thermal charge
      recombination events were determined; in some cases, measurements on suitable
      donor-sensitizer or sensitizer-acceptor dyads were necessary. In the case of the
      ruthenium and iridium triads, the fully charge-separated state is formed in
      nearly quantitative yield.

PMID- 22621321
TI  - Catalytic protein modification with dirhodium metallopeptides: specificity in
      designed and natural systems.
AB  - In this study, we present advances in the use of rhodium(II) metallopeptides for
      protein modification. Site-specific, proximity-driven modification is enabled by
      the unique combination of peptide-based molecular recognition and a rhodium
      catalyst capable of modifying a wide range of amino-acid side chains. We explore
      catalysis based on coiled-coil recognition in detail, providing an understanding
      of the determinants of specificity and culminating in the demonstration of
      orthogonal modification of separate proteins in cell lysate. In addition, the
      concepts of proximity-driven catalysis are extended to include modification of
      the natural Fyn SH3 domain with metallopeptides based on a known proline-rich
      peptide ligand. The development of orthogonal catalyst-substrate pairs for
      modification in lysate, and the extension of these methods to new natural protein
      domains, highlight the capabilities for new reaction design possible in chemical
      approaches to site-specific protein modification.

PMID- 22621322
TI  - New terpenoids from Mentha pulegium L. and their antimicrobial activity.
AB  - In addition to one previously reported compound: two new terpenoidal compounds
      1alpha, 6betadimethyl-5beta-hydroxy-4beta-(prop-1-en-2-yl)-decahydronaphthalen-2
      one (1) and 1-(O-beta-D-glucopyranosyl)-2,7-dimethyloct-5-en-3-one (2) were
      isolated from the chloroformic extract of Mentha pulegium L. The structure
      elucidation of these compounds was based primarily on 1D and 2D-nuclear magnetic
      resonance analyses. Compound 1 displayed moderate anti-MRSa (IC50 8.5 ug mL(-1)).

PMID- 22621320
TI  - Myostatin is a novel tumoral factor that induces cancer cachexia.
AB  - Humoral and tumoral factors collectively promote cancer-induced skeletal muscle
      wasting by increasing protein degradation. Although several humoral proteins,
      namely TNFalpha (tumour necrosis factor alpha) and IL (interleukin)-6, have been
      shown to induce skeletal muscle wasting, there is a lack of information regarding
      the tumoral factors that contribute to the atrophy of muscle during cancer
      cachexia. Therefore, in the present study, we have characterized the secretome of
      C26 colon cancer cells to identify the tumoral factors involved in cancer-induced
      skeletal muscle wasting. In the present study, we show that myostatin, a
      procachectic TGFbeta (transforming growth factor beta) superfamily member, is
      abundantly secreted by C26 cells. Consistent with myostatin signalling during
      cachexia, treating differentiated C2C12 myotubes with C26 CM (conditioned medium)
      resulted in myotubular atrophy due to the up-regulation of muscle-specific E3
      ligases, atrogin-1 and MuRF1 (muscle RING-finger protein 1), and enhanced
      activity of the ubiquitin-proteasome pathway. Furthermore, the C26 CM also
      activated ActRIIB (activin receptor type II B)/Smad and NF-kappaB (nuclear factor
      kappaB) signalling, and reduced the activity of the IGF-I (insulin-like growth
      factor 1)/PI3K (phosphoinositide 3-kinase)/Akt pathway, three salient molecular
      features of myostatin action in skeletal muscles. Antagonists to myostatin
      prevented C26 CM-induced wasting in muscle cell cultures, further confirming that
      tumoral myostatin may be a key contributor in the pathogenesis of cancer
      cachexia. Finally, we show that treatment with C26 CM induced the autophagy
      lysosome pathway and reduced the number of mitochondria in myotubes. These two
      previously unreported observations were recapitulated in skeletal muscles
      collected from C26 tumour-bearing mice.

PMID- 22621323
TI  - Reducing maternal deaths through state maternal mortality review.
AB  - BACKGROUND: Illinois has one of the highest rates of maternal death in the United
      States, and in 2000, the Illinois Maternal Mortality Review Committee (MMRC) was
      created to address this high rate of maternal death. METHODS: This is a detailed
      description of the development of the MMRC, its process of review, its impact on
      the state's attention to maternal mortality and its obstetric hospitals, and a
      summary of its initial findings. RESULTS: The Illinois MMRC, specifically
      designed to be multidisciplinary, was created to provide secondary review of
      select maternal deaths. Between 2000 and 2010, 45 of the 93 deaths reviewed had
      complete analysis. Hemorrhage was the leading cause of death, and 69% of all
      cases were deemed potentially avoidable. Compared to the primary required review
      conducted by the State Perinatal Center, the secondary review by the MMRC changed
      the cause of death in 20% of cases and changed the determination of avoidability
      in 36% of cases. Based on these findings and advocacy by the MMRC, in 2008,
      Illinois mandated that every M.D. and R.N. provider working in the obstetric unit
      of every obstetric hospital must complete the maternal hemorrhage education
      program. CONCLUSIONS: The MMRC has had a positive impact on Illinois' approach to
      reducing maternal deaths by being instrumental in getting the state to mandate
      that every obstetric hospital must comply with the Obstetric Hemorrhage Education
      Project to maintain its credentials. Further, the high rates at which cause of
      death and potential avoidability of death were changed by the MMRC underscore the
      need for multidisciplinary independent review of maternal deaths to achieve more
      accurate data and, hence, ultimately institute focused interventions to decrease
      preventable deaths.

PMID- 22621324
TI  - Genetic mapping and identification of QTL for earliness in the globe
      artichoke/cultivated cardoon complex.
AB  - BACKGROUND: The Asteraceae species Cynara cardunculus (2n = 2x = 34) includes the
      two fully cross-compatible domesticated taxa globe artichoke (var. scolymus L.)
      and cultivated cardoon (var. altilis DC). As both are out-pollinators and suffer
      from marked inbreeding depression, linkage analysis has focussed on the use of a
      two way pseudo-test cross approach. RESULTS: A set of 172 microsatellite (SSR)
      loci derived from expressed sequence tag DNA sequence were integrated into the
      reference C. cardunculus genetic maps, based on segregation among the F1 progeny
      of a cross between a globe artichoke and a cultivated cardoon. The resulting maps
      each detected 17 major linkage groups, corresponding to the species' haploid
      chromosome number. A consensus map based on 66 co-dominant shared loci (64 SSRs
      and two SNPs) assembled 694 loci, with a mean inter-marker spacing of 2.5 cM.
      When the maps were used to elucidate the pattern of inheritance of head
      production earliness, a key commercial trait, seven regions were shown to harbour
      relevant quantitative trait loci (QTL). Together, these QTL accounted for up to
      74% of the overall phenotypic variance. CONCLUSION: The newly developed consensus
      as well as the parental genetic maps can accelerate the process of tagging and
      eventually isolating the genes underlying earliness in both the domesticated C.
      cardunculus forms. The largest single effect mapped to the same linkage group in
      each parental maps, and explained about one half of the phenotypic variance, thus
      representing a good candidate for marker assisted selection.

PMID- 22621325
TI  - Health status and well-being of older adults living in the community and in
      residential care settings: are differences influenced by age?
AB  - The objective is to identify the differences and the main factors influencing
      health status and well-being variables between institutionalized and non
      institutionalized older adults, as well as the interaction effect of
      institutionalization and age. Data on a total of 468 older adults from a national
      survey on non-institutionalized and from a study on institutionalized older
      people were analyzed. Socio-demographic variables and measures on well-being
      (Personal Well-being Index, PWI), health status (EQ-5D), functional ability
      (Barthel Index), depression (Hospital Anxiety and Depression Scale-Depression
      subscale), loneliness and comorbidity were used. Analysis of variance and Kruskal
      Wallis tests to examine differences between groups and multiple regression
      analyses to identify factors associated to health and well-being were performed.
      Significant differences in health status variables, but not in well-being were
      detected between groups. Controlling for age, differences in health status (EQ
      VAS) were found to be not significant in both groups. In the non
      institutionalized group, people aged 78 years or more reported a significantly
      lower well-being (PWI) than younger counterparts. Step-wise multiple regression
      analysis showed that depression, functional dependence, loneliness and sex were
      associated with health status; while depression, health status, loneliness and
      the interaction of age-institutionalization were related to well-being. The
      results suggest that age influences community-dwelling older adults' well-being
      to a greater extent than it does to institutionalized older people. This finding
      has implications for resource allocation and interventions addressed to improve
      health and well-being in older adults.

PMID- 22621326
TI  - Resuscitation of very preterm infants with 30% vs. 65% oxygen at birth: study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Resuscitation at birth with 100% oxygen is known to increase the
      oxidative burden with concomitant deleterious effects. Although fractions of
      inspired oxygen (FiO2) < 100% are widely used in preterm infants, starting
      resuscitation at a (too) low FiO2 may result in hypoxia. The objective of this
      study is to compare the safety and efficacy of resuscitating very preterm infants
      with an initial FiO2 of 30% versus 65%. METHODS/DESIGN: In this double-blind,
      randomized controlled trial, 200 very preterm infants with a gestational age < 32
      weeks will be randomized to start resuscitation after birth with either 30% or
      65% oxygen. The FiO2 will be adjusted based on oxygen saturation measured by
      pulse oximetry (SpO2) and pulse rate (which should be over 100 beats per minute)
      in order to achieve a target SpO2 of 88-94% at 10 min of life. The FiO2 and pulse
      oximetry data will be continuously recorded.The primary outcome is survival
      without bronchopulmonary dysplasia, as assessed by a physiological test at 36
      weeks postmenstrual age. The secondary outcomes include the time to achieve SpO2
      > 88%, Apgar score at 5 min, cumulative O2 exposure, oxidative stress (as
      determined by glutathione synthesis and oxidative stress markers), retinopathy of
      prematurity, brain injury and neurodevelopmental outcome at 2 years of age.This
      study will provide insight into determining the appropriate initial FiO2 to start
      resuscitation of very preterm infants. TRIAL REGISTRATION:
      http://www.trialregister.nl, NTR243.

PMID- 22621327
TI  - Pain in postsurgical orthopedic rehabilitation: a multicenter study.
AB  - OBJECTIVE: The aim of this study was to quantify and characterize pain in
      patients undergoing lower limb postsurgical orthopedic rehabilitation and to
      investigate the impact of pain in slowing or interrupting their rehabilitation.
      DESIGN: The study was designed as a multicenter cross-sectional study. SETTING:
      The study was set in rehabilitation departments of the Don Gnocchi Foundation.
      SUBJECTS: The study subjects were the inpatients attending rehabilitation.
      INTERVENTIONS: There were no interventions used in the study. OUTCOME MEASURES:
      Pain intensity was measured with a numeric rating scale (NRS); pain
      characteristics were assessed with the McGill Pain Questionnaire and the ID Pain
      (able to discriminate nociceptive from neuropathic pain). Quality of life (QoL)
      was measured with the Short Form 36 Health Status Survey. A semi-structured
      questionnaire on pain occurrence, impact, and management was administered by the
      physiotherapist in charge of the patients and by the physician. RESULTS: We
      studied 139 patients, 82% of whom complained of at least moderate pain (NRS >=
      3). According to ID pain, 45.6% patients complained of probable (33.8%) or highly
      probable (11.8%) neuropathic pain. A higher pain intensity was significantly
      related to the probability of having neuropathic pain (P < 0.001). Patients with
      more severe pain reported lower physical and mental QoL scores. In 38.6% of
      cases, pain interfered with the rehabilitation process, and in 18.5% it was the
      cause of physical therapy discontinuation. CONCLUSIONS: In light of the high
      occurrence and intensity of pain in the sample, and of the significant impact on
      the rehabilitation program, clinicians should pay more attention to pain,
      especially neuropathic pain, in postsurgical patients. Tailored pain
      pharmacological therapy could possibly improve patient compliance during the
      rehabilitation process and enhance long-term outcomes.

PMID- 22621328
TI  - 2,6-Diacylnaphthalene-1,8:4,5-bis(dicarboximides): synthesis, reduction
      potentials, and core extension.
AB  - 2,6-Diacyl derivatives of naphthalene-1,8:4,5-bis(dicarboximide)s have been
      synthesized via Stille coupling reactions of the corresponding 2,6-distannyl
      derivative with acyl halides. Reaction of these diketones with hydrazine gave
      phthalazino[6,7,8,1-lmna]pyridazino[5,4,3-gh][3,8]phenanthroline-5,11(4H,10H)
      dione fused-ring derivatives. The products were characterized by UV-vis
      absorption spectroscopy and electrochemistry, modeled using density functional
      theory calculations, and, in some cases, studied and compared using single
      crystal X-ray diffraction.

PMID- 22621329
TI  - Adenosine-triggered elimination of methylene blue noncovalently bound to
      immobilized functional dsDNA-aptamer constructs.
AB  - Immobilization and electrochemical characterization of specially designed
      functional DNA-aptamer constructs are of great importance for the development of
      versatile biosensors (not limited to gene analysis) and the investigation of
      molecular interactions between DNA and other molecules. We have constructed a
      "DNA conformational switch" by incorporating the antiadenosine aptamer sequence
      in the middle of an otherwise cDNA double helix, as its structural change
      responds to the presence of small molecule ligands (e.g., adenosine). In
      particular, methylene blue (MB) was used as a model system to probe the rather
      complex interaction modes between small redox molecules and the dsDNA-aptamer
      construct. Besides intercalating with the double-stranded DNA stem, MB can stack
      with a single guanine base in the relatively unstructured aptamer domain or
      electrostatically bind to the DNA backbone. The decreased surface density of MB
      after adenosine binding indicated that the ligand-gated structural change of the
      dsDNA-aptamer construct can eliminate MB molecules that were originally bound to
      the aptamer domain but not those in the complementary stem.

PMID- 22621330
TI  - Sociodemographic correlates of eye care provider visits in the 2006-2009
      Behavioral Risk Factor Surveillance Survey.
AB  - BACKGROUND: Research has suggested that adults 40 years old and over are not
      following eye care visit recommendations. In the United States, the proportion of
      older adults is expected to increase drastically in the coming years. This has
      important implications for population ocular disease burden, given the
      relationship between older age and the development of many ocular diseases and
      conditions. Understanding individual level determinants of vision health could
      support the development of tailored vision health campaigns and interventions
      among our growing older population. Thus, we assessed correlates of eye care
      visits among participants of the Behavior Risk Factor Surveillance System (BRFSS)
      survey. We pooled and analyzed 2006-2009 BRFSS data from 16 States (N = 118,075).
      We assessed for the proportion of survey respondents 40 years of age and older
      reporting having visited an eye care provider within the past two years, two or
      more years ago, or never by socio-demographic characteristics. RESULTS: Nearly
      80% of respondents reported an eye care visit within the previous two years.
      Using the 'never visits' as the referent category, the groups with greater odds
      of having an ocular visit within the past two years included those: greater than
      70 years of age (OR = 6.8 [95% confidence interval = 3.7-12.6]), with college
      degree (5.2[3.0-8.8]), reporting an eye disease, (4.74[1.1-21.2]), diagnosed with
      diabetes (3.5[1.7-7.5]), of female gender (2.9[2.1-3.9]), with general health
      insurance (2.7[1.8-3.9]), with eye provider insurance coverage (2.1[1.5-3.0]),
      with high blood pressure (1.5[1.1-2.2]), and with moderate to extreme near vision
      difficulties (1.42[1.11-2.08]). CONCLUSION: We found significant variation by
      socio-demographic characteristics and some variation in state-level estimates in
      this study. The present findings suggest that there remains compliance gaps of
      screening guidelines among select socio-demographic sub-groups, as well as
      provide evidence and support to the CDC's Vision Health Initiative. This data
      further suggests that there remains a need for ocular educational campaigns in
      select socio-demographic subgroups and possibly policy changes to enhance
      insurance coverage.

PMID- 22621331
TI  - Optical resolution of aromatic alcohols using silica nanoparticles grafted with
      helicene.
AB  - Optically active silica nanoparticles, with a 70-nm diameter, grafted with (P)
      1,12-dimethyl-8-methoxycarbonylbenzo[c]phenanthrene-5-carboxyamide were
      synthesized, and their use in the kinetic resolution of aromatic alcohols was
      examined. Up to 61% ee for (S)-2,2-dimethyl-1-phenyl-1-propanol was obtained by a
      preferential precipitation of aggregates formed with (P)-nanoparticles.

PMID- 22621332
TI  - pH-Specific structural speciation of the ternary V(V)-peroxido-betaine system: a
      chemical reactivity-structure correlation.
AB  - Vanadium involvement in cellular processes requires deep understanding of the
      nature and properties of its soluble and bioavailable forms arising in aqueous
      speciations of binary and ternary systems. In an effort to understand the ternary
      vanadium-H(2)O(2)-ligand interactions relevant to that metal ion's biological
      role, synthetic efforts were launched involving the physiological ligands betaine
      (Me(3)N(+)CH(2)CO(2)(-)) and H(2)O(2). In a pH-specific fashion, V(2)O(5),
      betaine, and H(2)O(2) reacted and afforded three new, unusual, and unique
      compounds, consistent with the molecular formulation
      K(2)[V(2)O(2)(O(2))(4){(CH(3))(3)NCH(2)CO(2))}].H(2)O (1),
      (NH(4))(2)[V(2)O(2)(O(2))(4){(CH(3))(3)NCH(2)CO(2))}].0.75H(2)O (2), and
      {Na(2)[V(2)O(2)(O(2))(4){(CH(3))(3)NCH(2)CO(2))}(2)]}(n).4nH(2)O (3). All
      complexes 1-3 were characterized by elemental analysis; UV/visible, FT-IR, Raman,
      and NMR spectroscopy in solution and the solid state; cyclic voltammetry; TGA
      DTG; and X-ray crystallography. The structures of 1 and 2 reveal the presence of
      unusual ternary dinuclear vanadium-tetraperoxido-betaine complexes containing
      [(V(V)?O)(O(2))(2)] units interacting through long V-O bonds. The two V(V) ions
      are bridged through the oxygen terminal of one of the peroxide groups bound to
      the vanadium centers. The betaine ligand binds only one of the two V(V) ions. In
      the case of the third complex 3, the two vanadium centers are not immediate
      neighbors, with Na(+) ions (a) acting as efficient oxygen anchors and through Na
      O bonds holding the two vanadium ions in place and (b) providing for oxygen
      containing ligand binding leading to a polymeric lattice. In 1 and 3, interesting
      2D (honeycomb) and 1D (zigzag chains) topologies of potassium nine-coordinate
      polyhedra (1) and sodium octahedra (3), respectively, form. The collective
      physicochemical properties of the three ternary species 1-3 project the chemical
      role of the low molecular mass biosubstrate betaine in binding V(V)-diperoxido
      units, thereby stabilizing a dinuclear V(V)-tetraperoxido dianion. Structural
      comparisons of the anions in 1-3 with other known dinuclear V(V)-tetraperoxido
      binary anionic species provide insight into the chemical reactivity of V(V)
      diperoxido systems and their potential link to cellular events such as insulin
      mimesis and anitumorigenicity modulated by the presence of betaine.

PMID- 22621335
TI  - Fluorescence lifetime imaging--techniques and applications.
AB  - Fluorescence lifetime imaging (FLIM) uses the fact that the fluorescence lifetime
      of a fluorophore depends on its molecular environment but not on its
      concentration. Molecular effects in a sample can therefore be investigated
      independently of the variable, and usually unknown concentration of the
      fluorophore. There is a variety of technical solutions of lifetime imaging in
      microscopy. The technical part of this paper focuses on time-domain FLIM by
      multidimensional time-correlated single photon counting, time-domain FLIM by
      gated image intensifiers, frequency-domain FLIM by gain-modulated image
      intensifiers, and frequency-domain FLIM by gain-modulated photomultipliers. The
      application part describes the most frequent FLIM applications: Measurement of
      molecular environment parameters, protein-interaction measurements by Forster
      resonance energy transfer (FRET), and measurements of the metabolic state of
      cells and tissue via their autofluorescence. Measurements of local environment
      parameters are based on lifetime changes induced by fluorescence quenching or
      conformation changes of the fluorophores. The advantage over intensity-based
      measurements is that no special ratiometric fluorophores are needed. Therefore, a
      much wider selection of fluorescence markers can be used, and a wider range of
      cell parameters is accessible. FLIM-FRET measures the change in the decay
      function of the FRET donor on interaction with an acceptor. FLIM-based FRET
      measurement does not have to cope with problems like donor bleedthrough or
      directly excited acceptor fluorescence. This relaxes the requirements to the
      absorption and emission spectra of the donors and acceptors used. Moreover, FLIM
      FRET measurements are able to distinguish interacting and noninteracting
      fractions of the donor, and thus obtain independent information about distances
      and interacting and noninteracting protein fractions. This is information not
      accessible by steady-state FRET techniques. Autofluorescence FLIM exploits
      changes in the decay parameters of endogenous fluorophores with the metabolic
      state of the cells or the tissue. By resolving changes in the binding,
      conformation, and composition of biologically relevant compounds FLIM delivers
      information not accessible by steady-state fluorescence techniques.

PMID- 22621334
TI  - Local-regional control according to surrogate markers of breast cancer subtypes
      and response to neoadjuvant chemotherapy in breast cancer patients undergoing
      breast conserving therapy.
AB  - INTRODUCTION: Breast cancers of different molecular subtypes have different
      survival rates. The goal of this study was to identify patients at high risk for
      local-regional recurrence according to response to neoadjuvant chemotherapy and
      surrogate markers of molecular subtypes in patients undergoing breast conserving
      therapy (BCT). METHODS: Clinicopathologic data from 595 breast cancer patients
      who received neoadjuvant chemotherapy and BCT from 1997 to 2005 were identified.
      Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth
      factor receptor 2 (HER2) expression determined by immunohistochemistry were used
      to construct the following subtypes: ER+ or PR+ and HER2- (hormone receptor
      (HR)+/HER2-; 52%), ER+ or PR+ and HER2+ (HR+/HER2+; 9%), ER- and PR- and HER2+
      (HR-/HER2+; 7%) and ER- and PR- and HER2- (HR-/HER2-; 32%). Actuarial rates were
      calculated using the Kaplan-Meier method and compared using the log-rank test.
      Cox proportional hazards models were used for multivariate analysis (MVA).
      RESULTS: After a median follow-up of 64 months, the five-year local-regional
      recurrence (LRR)-free survival rate for all patients was 93.8%. The five-year LRR
      free survival rates varied by subtype: HR+/HER2- 97.0%, HR+/HER2+ 95.9%, HR
      /HER2+ 86.5% and HR-/HER2- 89.5% (P = 0.001). In addition to subtype, clinical
      stage III disease (90% vs. 95% for I/II, P = 0.05), high nuclear grade (92% vs.
      97% with low/intermediate grade, P = 0.03), presence of lymphovascular invasion
      (LVI) (89% vs. 95% in those without LVI, P = 0.02) and four or more positive
      lymph nodes on pathologic examination (87% vs. 95% with zero to three positive
      lymph nodes, P = 0.03) were associated with lower five-year LRR-free survival on
      univariate analysis. On MVA, HR-/HER2+ and HR-/HER2- subtypes and disease in four
      or more lymph nodes were associated with decreased LRR-free survival. A
      pathologic complete response (pCR) was associated with improved LRR-free
      survival. CONCLUSIONS: Patients with HR+/HER2- and HR+/HER2+ subtypes had
      excellent LRR-free survival regardless of tumor response to neoadjuvant
      chemotherapy. Patients with HR-/HER2+ and HR-/HER2- subtypes with poor response
      to neoadjuvant chemotherapy had worse LRR-free survival after BCT. Additional
      study is needed to determine the impact of trastuzumab on local-regional control
      in HER2+ tumors. Our data suggest that patients with HR-/HER2- subtype tumors not
      achieving pCR may benefit from novel strategies to improve local-regional
      control.

PMID- 22621333
TI  - Embryonic poly(A)-binding protein (EPAB) is required for oocyte maturation and
      female fertility in mice.
AB  - Gene expression during oocyte maturation and early embryogenesis up to zygotic
      genome activation requires translational activation of maternally-derived mRNAs.
      EPAB [embryonic poly(A)-binding protein] is the predominant poly(A)-binding
      protein during this period in Xenopus, mouse and human. In Xenopus oocytes, ePAB
      stabilizes maternal mRNAs and promotes their translation. To assess the role of
      EPAB in mammalian reproduction, we generated Epab-knockout mice. Although Epab(-/
      ) males and Epab(+/-) of both sexes were fertile, Epab(-/-) female mice were
      infertile, and could not generate embryos or mature oocytes in vivo or in vitro.
      Epab(-/-) oocytes failed to achieve translational activation of maternally-stored
      mRNAs upon stimulation of oocyte maturation, including Ccnb1 (cyclin B1) and Dazl
      (deleted in azoospermia-like) mRNAs. Microinjection of Epab mRNA into Epab(-/-)
      germinal vesicle stage oocytes did not rescue maturation, suggesting that EPAB is
      also required for earlier stages of oogenesis. In addition, late antral follicles
      in the ovaries of Epab(-/-) mice exhibited impaired cumulus expansion, and a 8
      fold decrease in ovulation, associated with a significant down-regulation of
      mRNAs encoding the EGF (epidermal growth factor)-like growth factors Areg
      (amphiregulin), Ereg (epiregulin) and Btc (betacellulin), and their downstream
      regulators, Ptgs2 (prostaglandin synthase 2), Has2 (hyaluronan synthase 2) and
      Tnfaip6 (tumour necrosis factor alpha-induced protein 6). The findings from the
      present study indicate that EPAB is necessary for oogenesis, folliculogenesis and
      female fertility in mice.

PMID- 22621336
TI  - Transfer of chirality from molecule to phase in self-assembled chiral block
      copolymers.
AB  - Here, we report the mechanisms of chiral transfer at various length scales in the
      self-assembly of enantiomeric chiral block copolymers (BCPs*). We show the
      evolution of homochirality from molecular chirality into phase chirality in the
      self-assembly of the BCPs*. The chirality of the molecule in the BCP* is
      identified from circular dichroism (CD) spectra, while the handedness of the
      helical conformation in the BCP* is determined from a split-type Cotton effect in
      vibrational circular dichroism spectra. Microphase separation of the BCP* is
      exploited to form a helical (H*) phase, and the handedness of helical
      nanostructure in the BCP* is directly visualized from transmission electron
      microscopy tomography. As examined by CD and fluorescence experiments,
      significant induced CD signals and a bathochromic shift of fluorescence emission
      for the achiral perylene moiety as a chemical junction of the BCPs* can be found
      while the concentration of the BCPs* in toluene solution is higher than the
      critical micelle concentration, suggesting a twisting and shifting mechanism
      initiating from the microphase-separated interface of the BCPs* leading to 
      formation of the H* phase from self-assembly.

PMID- 22621337
TI  - Representations of the subject 'woman' and the politics of abortion: an analysis
      of South African newspaper articles from 1978 to 2005.
AB  - A key element in cultural and gender power relations surrounding abortion is how
      women who undergo an abortion are represented in public talk. We analyse how
      women were named and positioned, and the attendant constructions of abortion, in
      South African newspaper articles on abortion from 1978 to 2005, a period during
      which there were radical political and legislative shifts. The name 'woman' was
      the most frequently used (70% of articles) followed by 'girl/teenager/child'
      (25%), 'mother' (25%), 'patient' (11%) and 'minor' (6%). The subject positionings
      enabled by these names were dynamic and complex and were interwoven with the
      localised, historical politics of abortion. The 'innocent mother' and the
      bifurcated 'patient' (woman/foetus) positionings were invoked in earlier epochs
      to promote abortion under medical conditions. The 'dangerous mother' and woman as
      'patient' positionings were used more frequently under liberal abortion
      legislation to oppose and to advocate for abortion, respectively. The positioning
      of the 'girl/teenager/child' as dependent and vulnerable was used in
      contradictory ways, both to oppose abortion and to argue for a liberalisation of
      restrictive legislation, depending on the attendant construction of abortion. The
      neutral naming of 'woman' was, at times, linked to the liberal imaginary of
      'choice'.

PMID- 22621338
TI  - Independent impact of body mass index and metabolic syndrome on the risk of type
      2 diabetes in Koreans.
AB  - BACKGROUND: Although obesity and metabolic syndrome have been associated with the
      risk of type 2 diabetes mellitus (T2DM), it is unclear whether obese or
      overweight people without metabolic syndrome are at increased risk for T2DM.
      METHODS: Clinical and laboratory data were assessed in 8,748 subjects without
      diabetes (5,707 men, 3,041 women; age 20-79 years) who underwent voluntary
      medical check-ups at a 5-year interval. The subjects were categorized by body
      mass index (BMI) and metabolic syndrome status at baseline, and the incidence of
      diabetes over 5 years was assessed. RESULTS: Of the 8,748 subjects, 308 (3.5%)
      developed T2DM over 5 years. Compared with normal weight (BMI <25.0 kg/m(2))
      individuals without metabolic syndrome, the adjusted odds ratios (ORs) were 1.61
      (1.13-2.29) and 4.93 (1.90-12.79) for overweight (BMI 25.0-29.9 kg/m(2)) and
      obese (BMI >=30.0 kg/m(2)) individuals without metabolic syndrome, respectively,
      and 6.94 (5.08-9.47) and 10.61 (5.59-20.14) for overweight and obese individuals
      with metabolic syndrome, respectively. Using the lower BMI cutoff points for
      Asian populations, compared with subjects with BMI <23 kg/m(2) without metabolic
      syndrome, the adjusted ORs for subjects with BMI 23-27.4 kg/m(2) and BMI >=27.5
      kg/m(2) without metabolic syndrome were 2.64 (1.74-4.00) and 4.31 (2.36-7.86),
      respectively, and 10.11 (6.53-15.67) and 16.69 (10.40-26.77), respectively, for
      those with metabolic syndrome. CONCLUSIONS: Overweight/obesity and metabolic
      syndrome both are significant risk factors for development of T2DM in Koreans,
      and overweight or obesity without metabolic syndrome should not be considered a
      harmless condition. The lower BMI cutoffs for Asian populations can be useful in
      predicting risk of T2DM in Koreans.

PMID- 22621339
TI  - Genetic variations of patients with familial or multiple melanoma in Southern
      Brazil.
AB  - BACKGROUND: Patients with familial melanoma or multiple primary melanoma
      represent a high-risk population to hereditary melanoma. Mutations in
      susceptibility genes, such as CDKN2A, CDK4 and MC1R, have been associated with
      the development of melanoma. OBJECTIVES: The purpose of this study was to
      determine the genotypic background of patients with familial and/or multiple
      melanoma in southern Brazil. METHODS: This study analysed 33 cases (5 patients
      with multiple primary melanoma and 28 patients from families with at least two
      well documented cases) and 29 controls. Genomic analysis of CDKN2A and CDK4 genes
      by PCR-SSCP analysis and sequencing and direct sequencing of MC1R were performed
      in all individuals. RESULTS: No functional mutations in CDKN2A or CDK4 were
      detected in the 62 individuals. Infrequent variants in polymorphic loci of CDKN2A
      gene were identified in 15 participants (24.2%) and 24/33 (72.8%) cases and 19/27
      (70.4%) controls reported at least one infrequent variant in MC1R (P = 0.372).
      Furthermore, a non-significant tendency towards an association between melanoma
      risk and MC1R variants G274A and C451T and a non-significant linear tendency to
      the number of infrequent high-risk variants in MC1R were observed. CONCLUSIONS:
      These results suggest that in southern Brazilian population, CDKN2A or CDK4
      germinal alterations may have a weaker influence than previously thought and
      environmental risk factors may play a central role in melanoma susceptibility.
      However, considering the tendency observed for gene MC1R, low-penetrance genes
      may be a relevant aetiological factor in southern Brazil with fair skin
      population and high sunlight exposure.

PMID- 22621340
TI  - Development of simple sequence repeat (SSR) markers from a genome survey of
      Chinese bayberry (Myrica rubra).
AB  - BACKGROUND: Chinese bayberry (Myrica rubra Sieb. and Zucc.) is a subtropical
      evergreen tree originating in China. It has been cultivated in southern China for
      several thousand years, and annual production has reached 1.1 million tons. The
      taste and high level of health promoting characters identified in the fruit in
      recent years has stimulated its extension in China and introduction to Australia.
      A limited number of co-dominant markers have been developed and applied in
      genetic diversity and identity studies. Here we report, for the first time, a
      survey of whole genome shotgun data to develop a large number of simple sequence
      repeat (SSR) markers to analyse the genetic diversity of the common cultivated
      Chinese bayberry and the relationship with three other Myrica species. RESULTS:
      The whole genome shotgun survey of Chinese bayberry produced 9.01Gb of sequence
      data, about 26x coverage of the estimated genome size of 323 Mb. The genome
      sequences were highly heterozygous, but with little duplication. From the initial
      assembled scaffold covering 255 Mb sequence data, 28,602 SSRs (>=5 repeats) were
      identified. Dinucleotide was the most common repeat motif with a frequency of
      84.73%, followed by 13.78% trinucleotide, 1.34% tetranucleotide, 0.12%
      pentanucleotide and 0.04% hexanucleotide. From 600 primer pairs, 186 polymorphic
      SSRs were developed. Of these, 158 were used to screen 29 Chinese bayberry
      accessions and three other Myrica species: 91.14%, 89.87% and 46.84% SSRs could
      be used in Myrica adenophora, Myrica nana and Myrica cerifera, respectively. The
      UPGMA dendrogram tree showed that cultivated Myrica rubra is closely related to
      Myrica adenophora and Myrica nana, originating in southwest China, and very
      distantly related to Myrica cerifera, originating in America. These markers can
      be used in the construction of a linkage map and for genetic diversity studies in
      Myrica species. CONCLUSION: Myrica rubra has a small genome of about 323 Mb with
      a high level of heterozygosity. A large number of SSRs were identified, and 158
      polymorphic SSR markers developed, 91% of which can be transferred to other
      Myrica species.

PMID- 22621341
TI  - The influence of corneal astigmatism on retinal nerve fiber layer thickness and
      optic nerve head parameter measurements by spectral-domain optical coherence
      tomography.
AB  - BACKGROUND: To evaluate the influence of corneal astigmatism (CA) on retinal
      nerve fiber layer (RNFL) thickness and optic nerve head(ONH) parameters measured
      with spectral-domain optical coherence tomography (OCT) in high myopes patients
      before refractive surgery. METHODS: Seventy eyes of 35 consecutive refractive
      surgery candidates were included in this study. The mean age of the subjects was
      26.42 +/- 6.95 years, the average CA was -1.17 diopters (D; SD 0.64; range -0.2
      to-3.3D), All subjects in this study were WTR CA. 34 eyes were in the normal CA
      group with a mean CA was -0.67 +/- 0.28D, 36 eyes were in the high CA group with
      an average CA of -1.65 +/- 0.49D. All subjects underwent ophthalmic examination
      and imaging with the Cirrus HD OCT. RESULTS: No significant difference was noted
      in the average cup-to-disk ratio, vertical cup-to-disk ratio and cup volume (all
      P values > 0.05). Compared with the normal CA group, the high CA group had a
      larger disc area and rim area, thinner RNFL thickness in the temporal quadrant,
      and the superotemporal and inferotemporal peaks were farther to the temporal
      horizon (All P values < 0.05). There were no significant differences between the
      two groups in global average RNFL thickness, as well as superior, nasal and
      inferior quadrant RNFL thickness (all P values > 0.05). CONCLUSIONS: The degree
      of with-the-rule CA should be considered when interpreting ONH parameters and
      peripapillary RNFL thickness measured by the Cirrus HD OCT. VIRTUAL SLIDES: The
      virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1148475676881895.

PMID- 22621342
TI  - Assessment of eight HPV vaccination programs implemented in lowest income
      countries.
AB  - BACKGROUND: Cervix cancer, preventable, continues to be the third most common
      cancer in women worldwide, especially in lowest income countries. Prophylactic
      HPV vaccination should help to reduce the morbidity and mortality associated with
      cervical cancer. The purpose of the study was to describe the results of and key
      concerns in eight HPV vaccination programs conducted in seven lowest income
      countries through the Gardasil Access Program (GAP). METHODS: The GAP provides
      free HPV vaccine to organizations and institutions in lowest income countries.
      The HPV vaccination programs were entirely developed, implemented and managed by
      local institutions. Institutions submitted application forms with institution
      characteristics, target population, communication delivery strategies. After
      completion of the vaccination campaign (3 doses), institutions provided a final
      project report with data on doses administered and vaccination models. Two
      indicators were calculated, the program vaccination coverage and adherence.
      Qualitative data were also collected in the following areas: government and
      community involvement; communication, and sensitization; training and logistics
      resources, and challenges. RESULTS: A total of eight programs were implemented in
      seven countries. The eight programs initially targeted a total of 87,580 girls,
      of which 76,983 received the full 3-dose vaccine course, with mean program
      vaccination coverage of 87.8%; the mean adherence between the first and third
      doses of vaccine was 90.9%. Three programs used school-based delivery models, 2
      used health facility-based models, and 3 used mixed models that included schools
      and health facilities. Models that included school-based vaccination were most
      effective at reaching girls aged 9-13 years. Mixed models comprising school and
      health facility-based vaccination had better overall performance compared with
      models using just one of the methods. Increased rates of program coverage and
      adherence were positively correlated with the number of vaccination sites.
      Qualitative key insights from the school models showed a high level of
      coordination and logistics to facilitate vaccination administration, a lower risk
      of girls being lost to follow-up and vaccinations conducted within the academic
      year limit the number of girls lost to follow-up. CONCLUSION: Mixed models that
      incorporate both schools and health facilities appear to be the most effective at
      delivering HPV vaccine. This study provides lessons for development of public
      health programs and policies as countries go forward in national decision-making
      for HPV vaccination.

PMID- 22621343
TI  - Dynamic evolution of bz orthologous regions in the Andropogoneae and other
      grasses.
AB  - Genome structure exhibits remarkable plasticity within Zea mays. To examine how
      haplotype structure has evolved within the Andropogoneae tribe, we have analyzed
      the bz gene-rich region of maize (Zea mays), the Zea teosintes mays ssp.
      mexicana, luxurians and diploperennis, Tripsacum dactyloides, Coix lacryma-jobi
      and Sorghum propinquum. We sequenced and annotated BAC clones from these species
      and re-annotated the orthologous Sorghum bicolor region. Gene colinearity in the
      region is well conserved within the genus Zea. However, the orthologous regions
      of Coix and Sorghum exhibited several micro-rearrangements relative to Zea,
      including addition, truncation and deletion of genes. The stc1 gene, involved in
      the production of a terpenoid insect defense signal, is evolving particularly
      fast, and its progressive disappearance from some species is occurring by
      microhomology-mediated recombination. LTR retrotransposons are the main
      contributors to the dynamic evolution of the bz region. Common transposon
      insertion sites occur among haplotypes from different Zea mays sub-species, but
      not outside the species. As in Zea, different patterns of interspersion between
      genes and retrotransposons are observed in Sorghum. We estimate that the mean
      divergence times between maize and Tripsacum, Coix and Sorghum are 8.5, 12.1 and
      12.4 million years ago, respectively, and that between Coix and Sorghum is 9.3
      million years ago. A comparison of the bz orthologous regions of Zea, Sorghum and
      Coix with those of Brachypodium, Setaria and Oryza allows us to infer how the
      region has evolved by addition and deletion of genes in the approximately 50
      million years since these genera diverged from a common progenitor.

PMID- 22621344
TI  - Moss-based production of asialo-erythropoietin devoid of Lewis A and other plant
      typical carbohydrate determinants.
AB  - Protein therapeutics represent one of the most increasing areas in the
      pharmaceutical industry. Plants gain acceptance as attractive alternatives for
      high-quality and economical protein production. However, as the majority of
      biopharmaceuticals are glycoproteins, plant-specific N-glycosylation has to be
      taken into consideration. In Physcomitrella patens (moss), glyco-engineering is
      an applicable tool, and the removal of immunogenic core xylose and fucose
      residues was realized before. Here, we present the identification of the enzymes
      that are responsible for terminal glycosylation (alpha1,4 fucosylation and
      beta1,3 galactosylation) on complex-type N-glycans in moss. The terminal
      trisaccharide consisting of alpha1,4 fucose and beta1,3 galactose linked to N
      acetylglucosamine forms the so-called Lewis A epitope. This epitope is rare on
      moss wild-type proteins, but was shown to be enriched on complex-type N-glycans
      of moss-produced recombinant human erythropoietin, while unknown from the native
      human protein. Via gene targeting of moss galactosyltransferase and
      fucosyltransferase genes, we identified the gene responsible for terminal
      glycosylation and were able to completely abolish the formation of Lewis A
      residues on the recombinant biopharmaceutical.

PMID- 22621345
TI  - Photoelectrochemical properties of TiO2 nanowire arrays: a study of the
      dependence on length and atomic layer deposition coating.
AB  - We report that the length and surface properties of TiO(2) nanowires can have a
      dramatic effect on their photoelectrochemical properties. To study the length
      dependence, rutile TiO(2) nanowires (0.28-1.8 MUm) were grown on FTO substrates
      with different reaction times (50-180 min) using a hydrothermal method. Nanowires
      show an increase in photocurrent with length, and a maximum photocurrent of 0.73
      mA/cm(2) was measured (1.5 V vs RHE) for 1.8 MUm long nanowires under AM 1.5G
      simulated sunlight illumination. While the incident photon to current conversion
      efficiency (IPCE) increases linearly with photon absorptance (1-10(
      alpha*length)) with near band gap illumination (lambda = 410 nm), it decreases
      severely at shorter wavelengths of light for longer nanowires due to poor
      electron mobility. Atomic layer deposition (ALD) was used to deposit an epitaxial
      rutile TiO(2) shell on nanowire electrodes which enhanced the photocatalytic
      activity by 1.5 times (1.5 V vs RHE) with 1.8 MUm long nanowires, reaching a
      current density of 1.1 mA/cm(2) (61% of the maximum photocurrent for rutile
      TiO(2)). Additionally, by fixing the epitaxial rutile shell thickness and
      studying photoelectrochemical (PEC) properties of different nanowire lengths
      (0.28-1.8 MUm), we found that the enhancement of current increases with length.
      These results demonstrate that ALD coating improves the charge collection
      efficiency from TiO(2) nanowires due to the passivation of surface states and an
      increase in surface area. Therefore, we propose that epitaxial coating on
      materials is a viable approach to improving their energy conversion efficiency.

PMID- 22621346
TI  - Prediction of neuroprotective treatment efficiency using a HRMAS NMR-based
      statistical model of refractory status epilepticus on mouse: a metabolomic
      approach supported by histology.
AB  - This work presents a model combining quantitative proton HRMAS NMR data and PLS
      DA for neuropathology and neuroprotection evaluation. Metabolic data were also
      confronted to histopathological results obtained using the same experimental
      conditions. Soman, when not lethal, can induce status epilepticus (SE), brain
      damage, histological lesions, and profound cerebral metabolic disorders as
      revealed using (1)H HRMAS NMR. Our challenge was to evaluate delayed treatments,
      which could control refractory SE and avoid brain lesions. For this aim, we have
      built a statistical model of soman intoxication describing brain metabolite
      evolution during 7 days. We have then used this model to evaluate the efficiency
      of a combination of ketamine/atropine (KET/AS) administrated 1 and 2 h after SE
      induction, compared to the immediate anticonvulsant therapy midazolam/atropine
      sulfate (MDZ/AS). Furthermore, quantitation of HRMAS NMR data allowed us to
      follow individual evolution of 17 metabolites. N-Acetylaspartate, lactate, or
      taurine presented a long lasting disruption, while glutamine, alanine,
      glycerophosphocholine and myo-inositol showed disruptions for 3 days with a
      reversion at day 7. These changes were completely normalized by the
      administration of MDZ/AS. Interestingly, they were also almost completely
      reversed by KET/AS 1 h postsoman. This work suggests further the predictive
      interest of HRMAS and PLS-DA for neuropathology/neuroprotection studies and also
      confirms, on the metabolic aspects, the neuroprotective potentials of KET/AS
      combinations for the delayed treatment of soman-induced SE.

PMID- 22621347
TI  - Tetranuclear [Co-Gd]2 complexes: aiming at a better understanding of the 3d-Gd
      magnetic interaction.
AB  - Tetranuclear [Co-Gd](2) complexes were prepared by using trianionic ligands
      possessing amide, imine, and phenol functions. The structural determinations show
      that the starting cobalt complexes present square planar or square pyramid
      environments that are preserved in the final tetranuclear [Co-Gd](2) complexes.
      These geometrical modifications of the cobalt coordination spheres induce changes
      in the cobalt spin ground states, going from S = 1/2 in the square planar to S =
      3/2 for the square pyramid environments. Depending on the ligand, the complexes
      display antiferromagnetic or ferromagnetic Co(II)-Gd(III) interactions. The
      temperature dependence of the magnetic susceptibility-temperature products
      indicate that the Co-Gd interaction is ferromagnetic when high spin Co ions are
      concerned and antiferromagnetic in the case of low spin Co ions. This different
      magnetic behavior can be explained if we observe that the singly occupied sigma
      d(x(2)-y(2)) orbital is populated (S = 3/2 Co ions) or unoccupied (S = 1/2 Co
      ions). Such an observation furnishes invaluable information for the understanding
      of the more general 3d-4f magnetic interactions.

PMID- 22621348
TI  - 20th International Symposium on Shiftwork and Working Time: biological
      mechanisms, recovery, and risk management in the 24-h society.
AB  - This dedicated issue of Chronobiology International is devoted to the selected
      proceedings of the 20th International Symposium on Shift Work and Working Time
      held in Stockholm, Sweden, 28 June to 1 July 2011. It constitutes the fifth such
      issue of the journal since 2004 dedicated to the selected proceedings to the
      meetings of the Working Time Society. The key theme of the 20th Symposium was
      "Biological Mechanisms, Recovery, and Risk Management in the 24-h Society." The
      collection of papers of this dedicated issue represents the best of contemporary
      research on the effects of night and rotating shift schedules on worker health
      and safety. The contents cover such topics as sleep restriction, injuries,
      health, and performance of night work and rotating shiftwork, plus light
      treatment as a countermeasure against the circadian disruption of shiftwork. The
      majority of the papers are observational field studies, including some of large
      sample size, and three studies are well-designed laboratory experiments.

PMID- 22621349
TI  - Mood, alertness, and performance in response to sleep deprivation and recovery
      sleep in experienced shiftworkers versus non-shiftworkers.
AB  - Previous studies have shown increased sleepiness and mood changes in
      shiftworkers, which may be due to sleep deprivation or circadian disruption. Few
      studies, however, have compared responses of experienced shiftworkers and non
      shiftworkers to sleep deprivation in an identical laboratory setting. The aim of
      this laboratory study, therefore, was to compare long-term shiftworkers and non
      shiftworkers and to investigate the effects of one night of total sleep
      deprivation (30.5 h of continuous wakefulness) and recovery sleep on psychomotor
      vigilance, self-rated alertness, and mood. Eleven experienced male shiftworkers
      (shiftwork >=5 yrs) were matched with 14 non-shiftworkers for age (mean +/- SD:
      35.7 +/- 7.2 and 32.5 +/- 6.2 yrs, respectively) and body mass index (BMI) (28.7
      +/- 3.8 and 26.6 +/- 3.4 kg/m(2), respectively). After keeping a 7-d self
      selected sleep/wake cycle (7.5/8 h nocturnal sleep), both groups entered a
      laboratory session consisting of a night of adaptation sleep and a baseline sleep
      (each 7.5/8 h), a sleep deprivation night, and recovery sleep (4-h nap plus 7.5/8
      h nighttime sleep). Subjective alertness and mood were assessed with the
      Karolinska Sleepiness Scale (KSS) and 9-digit rating scales, and vigilance was
      measured by the visual psychomotor vigilance test (PVT). A mixed-model regression
      analysis was carried out on data collected every hour during the sleep
      deprivation night and on all days (except for the adaptation day), at .25, 4.25,
      5.25, 11.5, 12.5, and 13.5 h after habitual wake-up time. Despite similar
      circadian phase (melatonin onset), demographics, food intake, body posture, and
      environmental light, shiftworkers felt significantly more alert, more cheerful,
      more elated, and calmer than non-shiftworkers throughout the laboratory study. In
      addition, shiftworkers showed a faster median reaction time (RT) compared to non
      shiftworkers, although four other PVT parameters did not differ between the
      groups. As expected, both groups showed a decrease in subjective alertness and
      PVT performance during and following the sleep deprivation night. Subjective
      sleepiness and most aspects of PVT performance returned to baseline levels after
      a nap and recovery sleep. The mechanisms underlying the observed differences
      between shiftworkers and non-shiftworkers require further study, but may be
      related to the absence of shiftwork the week prior to and during the laboratory
      study as well as selection into and out of shiftwork.

PMID- 22621350
TI  - Shiftwork and metabolic dysfunction.
AB  - Many of the health problems that are more prevalent among shiftworkers are
      thought to be linked to their heightened susceptibility to metabolic syndrome,
      i.e., the association of even moderate degrees of visceral obesity, dyslipidemia,
      abnormal blood pressure, and serum glucose levels in the same individual.
      Although previous studies have identified associations between shiftwork and
      metabolic syndrome, there is relatively little evidence to date of how the risk
      of developing it varies as a function of exposure to shiftwork. The current study
      seeks to confirm earlier findings of an association between shiftwork exposure
      and metabolic dysfunction, and to examine the impact of exposure duration, while
      adjusting for a number of covariates in the analyses. The analyses were based on
      data from VISAT, a study involving the measurement of physiological, behavioral,
      and subjective outcomes from 1757 participants, 989 being current or former
      shiftworkers. The sample comprised employed and retired wage earners, male and
      female, who were 32, 42, 52, and 62 yrs old. The first analysis sought to confirm
      previous findings of an association between exposure to shiftwork and the risk of
      developing metabolic syndrome. It indicated that participants who were or who had
      previously been shiftworkers (i.e., working schedules that involved rotating
      shifts; not being able to go to bed before midnight; having to get up before
      05:00 h; or being prevented from sleeping during the night) were more likely to
      exhibit symptoms of metabolic syndrome, after adjusting for age, sex,
      socioeconomic status, smoking, alcohol intake, perceived stress, and sleep
      difficulty (odds ratio [OR] 1.78; 95% confidence interval [CI] 1.03-3.08). The
      results suggest the association between shiftwork and metabolic syndrome cannot
      be fully accounted for by either higher levels of strain or increased sleep
      difficulty among shiftworkers, although it remains a possibility that either one
      or both of these factors may have played a contributing role. The second analysis
      addressed the issue of duration of exposure to shiftwork. Participants with >10
      yrs' experience of working rotating shifts were more likely to exhibit symptoms
      of metabolic syndrome than participants without exposure to shiftwork, i.e.,
      dayworkers, even after adjusting for age and sex (OR 1.96; 95% CI 1.03-3.75).
      Thus, the current study confirms the association between shiftwork exposure and
      metabolic syndrome. It also provides new information regarding the time course of
      the development of the illness as function of exposure duration, although this
      was only examined in relation to rotating shiftwork. It is concluded that those
      responsible for monitoring workers' health should pay particular attention to
      indices of metabolic dysfunction in workers who have been exposed to shiftwork
      for >10 yrs.

PMID- 22621351
TI  - Independent effects of sleep duration and body mass index on the risk of a work
      related injury: evidence from the US National Health Interview Survey (2004
      2010).
AB  - Fatigue has been linked to adverse safety outcomes, and poor quality or decreased
      sleep has been associated with obesity (higher body mass index, BMI).
      Additionally, higher BMI is related to an increased risk for injury; however, it
      is unclear whether BMI modifies the effect of short sleep or has an independent
      effect on work-related injury risk. To answer this question, the authors examined
      the risk of a work-related injury as a function of total daily sleep time and BMI
      using the US National Health Interview Survey (NHIS). The NHIS is an in-person
      household survey using a multistage, stratified, clustered sample design
      representing the US civilian population. Data were pooled for the 7-yr survey
      period from 2004 to 2010 for 101 891 "employed" adult subjects (51.7%; 41.1 +/-
      yrs of age [mean +/- SEM]) with data on both sleep and BMI. Weighted annualized
      work-related injury rates were estimated across a priori defined categories of
      BMI: healthy weight (BMI: <25), overweight (BMI: 25-29.99), and obese (BMI: >=30)
      and also categories of usual daily sleep duration: <6, 6-6.99, 7-7.99, 8-8.99,
      and >=9 h. To account for the complex sampling design, including stratification,
      clustering, and unequal weighting, weighted multiple logistic regression was used
      to estimate the risk of a work-related injury. The initial model examined the
      interaction among daily sleep duration and BMI, controlling for weekly working
      hours, age, sex, race/ethnicity, education, type of pay, industry, and
      occupation. No significant interaction was found between usual daily sleep
      duration and BMI (p = .72); thus, the interaction term of the final logistic
      model included these two variables as independent predictors of injury, along
      with the aforementioned covariates. Statistically significant covariates (p <=
      .05) included age, sex, weekly work hours, occupation, and if the worker was paid
      hourly. The lowest categories of usual sleep duration (<6 and 6-6.9 h) showed
      significantly (p <= .05) elevated injury risks than the referent category (7-8 h
      sleep), whereas sleeping >7-8 h did not significantly elevate risk. The adjusted
      injury risk odds ratio (OR) for a worker with a usual daily sleep of <6 h was
      1.86 (95% confidence interval [CI]: 1.37-2.52), and for 6-6.9 h it was 1.46 (95%
      CI: 1.18-1.80). With regards to BMI, the adjusted injury risk OR comparing
      workers who were obese (BMI: >=30) to healthy weight workers (BMI: <25) was 1.34
      (95% CI: 1.09-1.66), whereas the risk in comparing overweight workers (BMI: 25
      29.99) to healthy weight risk was elevated, but not statistically significant (OR
      = 1.08; 95% CI: .88-1.33). These results from a large representative sample of US
      workers suggest increase in work-related injury risk for reduced sleep regardless
      of worker's body mass. However, being an overweight worker also increases work
      injury risk regardless of usual daily sleep duration. The independent additive
      risk of these factors on work-related injury suggests a substantial, but at least
      partially preventable, risk.

PMID- 22621352
TI  - Sleep restriction masks the influence of the circadian process on sleep
      propensity.
AB  - Previous forced desynchrony studies have highlighted the close relationship
      between the circadian rhythms of core body temperature (CBT) and sleep
      propensity. In particular, these studies have shown that a "forbidden zone" for
      sleep exists on the rising limb of the CBT rhythm. In these previous studies, the
      length of the experimental day was either ultrashort (90 min), short (20 h), or
      long (28 h), and the ratio of sleep to wake was normal (i.e., 1:2). The aim of
      the current study was to examine the relative effects of the circadian and
      homeostatic processes on sleep propensity using a 28-h forced desynchrony
      protocol in which the ratio of sleep to wake was substantially lower than normal
      (i.e., 1:5). Twenty-seven healthy males lived in a time-isolation sleep
      laboratory for 11 consecutive days. Participants completed either a control (n =
      13) or sleep restriction (n = 14) condition. In both conditions, the protocol
      consisted of 2 * 24-h baseline days followed by 8 * 28-h forced desynchrony days.
      On forced desynchrony days, the control group had 9.3 h in bed and 18.7 h of
      wake, and the sleep restriction group had 4.7 h in bed and 23.3 h of wake. For
      all participants, each 30-s epoch of time in bed was scored as sleep or wake
      based on standard polysomnography recordings, and was also assigned a circadian
      phase (360 degrees  = 24 h) based on a cosine equation fitted to continuously
      recorded CBT data. For each circadian phase (i.e., 72 * 5 degrees  bins), sleep
      propensity was calculated as the percentage of epochs spent in bed scored as
      sleep. For the control group, there was a clear circadian rhythm in sleep
      propensity, with a peak of 98.5% at 5 degrees  (~05:20 h), a trough of 64.9% at
      245 degrees  (~21:20 h), and an average of 82.3%. In contrast, sleep propensity
      for the sleep restriction group was relatively high at all circadian phases, with
      an average of 96.7%. For this group, the highest sleep propensity (99.0%)
      occurred at 60 degrees  (~09:00 h), and the lowest sleep propensity (91.3%)
      occurred at 265 degrees  (~22:40 h). As has been shown previously, these current
      data indicate that with a normal sleep-to-wake ratio, the effect of the circadian
      process on sleep propensity is pronounced, such that a forbidden zone for sleep
      exists at a phase equivalent to evening time for a normally entrained individual.
      However, these current data also indicate that when the ratio of sleep to wake is
      substantially lower than normal, this circadian effect is masked. In particular,
      sleep propensity is very high at all circadian phases, including those that
      coincide with the forbidden zone for sleep. This finding suggests that if the
      homeostatic pressure for sleep is sufficiently high, then the circadian drive for
      wakefulness can be overridden. In future studies, it will be important to
      determine whether or not this masking effect occurs with less severe sleep
      restriction, e.g., with a sleep-to-wake ratio of 1:3.

PMID- 22621353
TI  - Time-of-day mediates the influences of extended wake and sleep restriction on
      simulated driving.
AB  - Although a nonlinear time-of-day and prior wake interaction on performance has
      been well documented, two recent studies have aimed to incorporate the influences
      of sleep restriction into this paradigm. Through the use of sleep-restricted
      forced desynchrony protocols, both studies reported a time-of-day * sleep
      restriction interaction, as well as a time-of-day * prior wake * sleep dose three
      way interaction. The current study aimed to investigate these interactions on
      simulated driving performance, a more complex task with ecological validity for
      the problem of fatigued driving. The driving performance of 41 male participants
      (mean +/- SD: 22.8 +/-2.2 yrs) was assessed on a 10-min simulated driving task
      with the standard deviation of lateral position (SDLAT) measured. Using a between
      group design, participants were subjected to either a control condition of 9.33 h
      of sleep/18.66 h of wake, a moderate sleep-restriction (SR) condition of 7 h of
      sleep/21 h of wake, or a severe SR condition of 4.66 h of sleep/23.33 h of wake.
      In each condition, participants were tested at 2.5-h intervals after waking
      across 7 * 28-h d of forced desynchrony. Driving sessions occurred at nine doses
      of prior wake, within six divisions of the circadian cycle based on core body
      temperature (CBT). Mixed-models analyses of variance (ANOVAs) revealed
      significant main effects of time-of-day, prior wake, sleep debt, and sleep dose
      on SDLAT. Additionally, significant two-way interactions of time-of-day * prior
      wake and time-of-day * sleep debt, as well as significant three-way interactions
      of time-of-day * prior wake * sleep debt and time-of-day * sleep debt * sleep
      dose were observed. Although limitations such as the presence of practice effects
      and large standard errors are noted, the study concludes with three findings. The
      main effects demonstrate that extending wake, reducing sleep, and driving at poor
      times of day all significantly impair driving performance at an individual level.
      In addition to this, combining either extended wake or a sleep debt with the
      early morning hours greatly decreases driving performance. Finally, operating
      under the influence of a reduced sleep dose can greatly decrease performance at
      all times of the day.

PMID- 22621354
TI  - Impact of layover length on sleep, subjective fatigue levels, and sustained
      attention of long-haul airline pilots.
AB  - Long-haul airline pilots often experience elevated levels of fatigue due to
      extended work hours and circadian misalignment of sleep and wake periods. During
      long-haul trips, pilots are typically given 1-3 d off between flights (i.e.,
      layover) to recover from, and prepare for, duty. Anecdotally, some pilots prefer
      long layovers because it maximizes the time available for recovery and
      preparation, but others prefer short layovers because it minimizes both the
      length of the trip, and the degree to which the body clock changes from "home
      time" to the layover time zone. The aim of this study was to examine the impact
      of layover length on the sleep, subjective fatigue levels, and capacity to
      sustain attention of long-haul pilots. Participants were 19 male pilots (10
      Captains, 9 First Officers) working for an international airline. Data were
      collected during an 11- or 12-d international trip. The trips involved (i) 4 d at
      home prior to the trip; (ii) an eastward flight of 13.5 h across seven time
      zones; (iii) a layover of either 39 h (i.e., short, n = 9) or 62 h (i.e., long, n
      = 10); (iv) a return westward flight of 14.3 h across seven time zones; and (v) 4
      d off at home after the trip. Sleep was recorded using a self-report sleep diary
      and wrist activity monitor; subjective fatigue level was measured using the Samn
      Perelli Fatigue Checklist; and sustained attention was assessed using the
      psychomotor vigilance task for a personal digital assistant (PalmPVT). Mixed
      model regression analyses were used to determine the effects of layover length
      (short, long) on the amount of sleep that pilots obtained during the trip, and on
      the pilots' subjective fatigue levels and capacity to sustain attention. There
      was no main effect of layover length on ground-based sleep or in-flight sleep,
      but pilots who had a short layover at the midpoint of their trip had higher
      subjective fatigue levels and poorer sustained attention than pilots who had a
      long layover. The results of this study indicate that a short layover during a
      long-haul trip does not substantially disrupt pilots' sleep, but it may result in
      elevated levels of fatigue during and after the trip. If short layovers are used,
      pilots should have a minimum of 4 d off to recover prior to their next long-haul
      trip.

PMID- 22621355
TI  - Adipokine levels are altered by shiftwork: a preliminary study.
AB  - Shiftwork is often associated with metabolic diseases, and in the past few years,
      several cytokines have been postulated to contribute to various diseases,
      including insulin resistance. The aim of this study was to compare the
      concentrations of adiponectin, tumor necrosis factor-alpha (TNF-alpha), and
      interleukin-6 (IL-6) in samples of young adult men exposed to a fixed (i) night
      shift (n = 9), working from 22:00 to 06:00 h; (ii) early morning shift (n = 6),
      working from 06:00 to 14:00 h; and (iii) day shift (n = 7), working from 08:00 to
      17:00 h. The fixed night-shift and early-morning-shift samples were considered
      collectively as a shiftworker group given their work times. Blood samples were
      collected during the regular working day at 4-h intervals over the course of 24
      h, thus totaling six samples. Morphological and physical activity parameters did
      not differ between the three groups. Total energy intake was lowest on the early
      morning shifts (p < .03). Both shiftworker groups ingested a significantly higher
      percentage of fat (p < .003) and a lower percentage of carbohydrate (p < .0005)
      than the day group. The early morning group had a lower mean 24-h level of
      adiponectin than the other two groups (p = .016), and both the early morning and
      night groups exhibited higher mean 24-h levels of TNF-alpha than the day group (p
      = .0001). The 24-h mean levels of IL-6 did not differ significantly between the
      groups (p = .147). None of the groups exhibited a significant circadian effect on
      adiponectin (p = .829), TNF-alpha (p = .779), or IL-6 (p = .979) levels. These
      results indicate that individuals who are enrolled in shiftwork are susceptible
      to alterations in the secretion of cytokines that are involved in insulin
      resistance and cardiovascular disease, both of which are known to affect this
      population.

PMID- 22621356
TI  - Effects of lifetime exposure to shiftwork on fitness for duty in police officers.
AB  - Aging and demographic changes in Europe and other global economies have led to a
      discussion about postponing the legal retirement age; however, health and safety
      consequences for the workforce have not yet been examined. Thus, the aim of this
      study was to investigate the effects of lifetime exposure to shiftwork on health
      impairments and fitness for duty. Two samples of the police force from one of the
      states of the Federal Republic of Germany were used. One sample was collected in
      2008-2009 with a self-administered Internet questionnaire (n = 705); the other
      sample was derived from employment records provided by the police force of the
      same federal state for the years 2002-2009 (n = 2460). Both samples contained
      information about the number of years worked in shiftwork across the entire
      working life and impairments to fitness for duty assessed by occupational
      physicians. Thus, the number of years of shiftwork until the diagnosis of the
      first reduction in fitness for duty could be calculated. Survival analyses were
      performed to estimate the risk (hazard rate) for experiencing a reduction in
      fitness for duty across lifetime exposure to shiftwork in years, controlling for
      age, sex, work type, and police district. Hazard estimates were compared across
      both samples to cross-validate the results. The findings indicated an increase in
      the risk of reduced fitness for duty with increasing number of years in shiftwork
      during the working life in both samples. The hazard rates followed an exponential
      trend, indicating a rapid increase in health impairments in particular beyond 20
      yrs of shiftwork. These findings were consistent in both samples, collected with
      different methods and over different time periods, thus indicating high validity.
      Therefore, occupational stress factors, such as exposure to shiftwork, need to be
      taken into account when discussing the postponement of the legal retirement age.

PMID- 22621357
TI  - Night work and mortality: prospective study among Finnish employees over the time
      span 1984 to 2008.
AB  - There is considerable evidence showing that night work is associated with
      increased morbidity, but only a few studies have focused on its relation to
      mortality. This study investigates the relationship between the type of working
      time arrangement (weekly night work/daytime work) and total and cause-specific
      mortality among men and women. The data consist of a representative working
      conditions survey of Finnish employees conducted in 1984 (2286 men/2216 women),
      which has been combined with register-based follow-up data from Statistics
      Finland covering the years 1985-2008. In the 1984 survey, the employees were
      asked if they worked during the night (23:00-06:00 h) and if so, how often. In
      this study, the authors compare employees who worked at night (121 men/89 women)
      to daytime employees who did not do night work (1325 men/1560 women). The
      relative risk of death was examined by Cox proportional hazards analyses adjusted
      for background (age, level of education, family situation, and county), health
      (longstanding illness, pain symptoms, smoking status, and psychological
      symptoms), and work-related factors (weekly working hours, physical and
      psychological demands, demands of learning at work, and perceived job
      insecurity). Female employees working at night had a 2.25-fold higher risk of
      mortality than female dayworkers (95% confidence interval [CI] 1.20-4.20) after
      adjustment for background and health- and work-related factors. In addition to
      total mortality, night work was also associated with tumor mortality. Female
      night workers had a 2.82-fold higher risk of tumor mortality than female
      dayworkers (95% CI 1.20-6.65) in the adjusted model. Among men, no such
      significant association was observed. The present study indicated that female
      night workers had a higher risk of both total and tumor mortality compared to
      female daytime employees. Additional research on the potential factors and
      mechanisms behind the association between night work and mortality is required.

PMID- 22621358
TI  - Alcohol consumption patterns of shiftworkers compared with dayworkers.
AB  - The detrimental effects of excessive alcohol consumption are well documented.
      There is some evidence that shiftworkers consume more alcohol than dayworkers as
      a sleep aid to compensate for sleep difficulties associated with work schedules.
      This study investigated drinking patterns between shiftworkers and dayworkers
      using the 2006 and 2007 waves from the Household Income and Labour Dynamics
      Survey. A subset of workers who were not in full-time study and had a single job
      were selected; participants who did not drink alcohol (n = 2090) were excluded.
      Using the 2001 Australian Government alcohol guidelines, alcohol consumption for
      risk of short-term harm (7+ standard drinks for men, 5+ for women) was
      investigated. The number of workers who drank alcohol "nearly every day" or
      "every day" was also examined. Some 13% of shiftworkers and 10% of those on
      standard schedules reported consuming alcohol at levels risky for short-term
      harm. Having a child less than 17 yrs (odds ratio [OR] = .39, 95% confidence
      interval [CI] = .22-.69), higher job demands (OR = .71, 95% CI = .58-.86), being
      female (OR = .45, 95% CI=. 26-.79), and being older (OR = .89, 95% CI = .87-.92)
      significantly reduced, whereas being a shiftworker (OR = 2.10, 95% CI = 1.08
      4.12) significantly increased, the odds of drinking alcohol in short-term risky
      levels. Nearly 10% of shiftworkers and 8% of those on standard schedules reported
      consuming alcohol in short-term risky levels at least weekly. Having a child less
      than 17 yrs (OR = .40, 95% CI = .22-.74), higher job demands (OR = .69, 95% CI =
      .56-.86), being female (OR = .28, 95% CI = .15-.53), and being older (OR = .92,
      95% CI = .89-.94) were associated with a significant reduction in the odds of
      consuming alcohol at risky levels at least weekly. Being a shiftworker was not
      associated with a significant increase in the odds of consuming alcohol at such
      risky levels at least weekly, but a trend was evident (OR = 1.47, 95% CI = .73
      3.00). Some 13.5% of shiftworkers and 21% of those on standard schedules reported
      consuming alcohol in any amount "near daily" or "daily." Working more hours than
      preferred (OR = 1.80, 95% CI = 1.12-2.89) and being older (OR = 1.10, 95% CI =
      1.07-1.13) were associated with a significant increase, and being female (OR =
      .18, 95% CI = .10-.33), and being a shiftworker (OR = .20, 95% CI = .09-.45) were
      associated with a significant decrease in the odds of consuming alcohol "daily"
      or "near daily." Overall, the results suggest that shiftworkers may be more
      likely to consume alcohol at levels considered to be risky for health in the
      short term. In contrast, they appear less likely to drink alcohol daily. This
      pattern is suggestive of "binge drinking" behavior.

PMID- 22621359
TI  - Photic resetting in night-shift work: impact on nurses' sleep.
AB  - The objective of this study was to quantify daytime sleep in night-shift workers
      with and without an intervention designed to recover the normal relationship
      between the endogenous circadian pacemaker and the sleep/wake cycle. Workers of
      the treatment group received intermittent exposure to full-spectrum bright light
      during night shifts and wore dark goggles during the morning commute home. All
      workers maintained stable 8-h daytime sleep/darkness schedules. The authors found
      that workers of the treatment group had daytime sleep episodes that lasted 7.1 +/
      .1 h (mean +/- SEM) versus 6.6 +/- .2 h for workers in the control group (p =
      .04). The increase in total sleep time co-occurred with a larger proportion of
      the melatonin secretory episode during daytime sleep in workers of the treatment
      group. The results of this study showed reestablishment of a phase angle that is
      comparable to that observed on a day-oriented schedule favors longer daytime
      sleep episodes in night-shift workers. (Author correspondence:
      diane.boivin@douglas.mcgill.ca ).

PMID- 22621360
TI  - Phototherapy and orange-tinted goggles for night-shift adaptation of police
      officers on patrol.
AB  - The aim of the present combined field and laboratory study was to assess
      circadian entrainment in two groups of police officers working seven consecutive
      8/8.5-h night shifts as part of a rotating schedule. Eight full-time police
      officers on patrol (mean age +/- SD: 29.8 +/- 6.5 yrs) were provided an
      intervention consisting of intermittent exposure to wide-spectrum bright light at
      night, orange-tinted goggles at sunrise, and maintenance of a regular
      sleep/darkness episode in the day. Orange-tinted goggles have been shown to block
      the melatonin-suppressing effect of light significantly more than neutral gray
      density goggles. Nine control group police officers (mean age +/- SD: 30.3 +/-
      4.1 yrs) working the same schedule were enrolled. Police officers were studied
      before, after (in the laboratory), and during (ambulatory) a series of seven
      consecutive nights. Urine samples were collected at wake time and bedtime
      throughout the week of night work and during laboratory visits (1 * /3 h)
      preceding and following the work week to measure urinary 6-sulfatoxymelatonin
      (UaMT6s) excretion rate. Subjective alertness was assessed at the start, middle,
      and end of night shifts. A 10-min psychomotor vigilance task was performed at the
      start and end of each shift. Both laboratory visits consisted of two 8-h sleep
      episodes based on the prior schedule. Saliva samples were collected 2 * /h during
      waking episodes to assay their melatonin content. Subjective alertness (3 * /h)
      and performance (1 * /2 h) were assessed during wake periods in the laboratory. A
      mixed linear model was used to analyze the progression of UaMt6s excreted during
      daytime sleep episodes at home, as well as psychomotor performance and subjective
      alertness during night shifts. Two-way analysis of variance (ANOVA) (factors:
      laboratory visit and group) were used to compare peak salivary melatonin and
      UaMT6s excretion rate in the laboratory. In both groups of police officers, the
      excretion rate of UaMT6s at home was higher during daytime sleep episodes at the
      end compared to the start of the work week (p < .001). This rate increased
      significantly more in the intervention than control group (p = .032). A
      significant phase delay of salivary melatonin was observed in both groups at the
      end of study (p = .009), although no significant between-group difference was
      reached. Reaction speed dropped, and subjective alertness decreased throughout
      the night shift in both groups (p < .001). Reaction speed decreased throughout
      the work week in the control group (p <= .021), whereas no difference was
      observed in the intervention group. Median reaction time was increased as of the
      5th and 6th nights compared to the 2nd night in controls (p <= .003), whereas it
      remained stable in the intervention group. These observations indicate better
      physiological adaptation in the intervention group compared to the controls.

PMID- 22621361
TI  - Assessment of a new dynamic light regimen in a nuclear power control room without
      windows on quickly rotating shiftworkers--effects on health, wakefulness, and
      circadian alignment: a pilot study.
AB  - The aim of the study was to test whether a new dynamic light regime would improve
      alertness, sleep, and adaptation to rotating shiftwork. The illumination level in
      a control room without windows at a nuclear power station was ~200 lux (straight
      forward horizontal gaze) using a weak yellow light of 200 lux, 3000 K (Philips
      Master TLD 36 W 830). New lighting equipment was installed in one area of the
      control room above the positions of the reactor operators. The new lights were
      shielded from the control group by a distance of >6 m, and the other operators
      worked at desks turned away from the new light. The new lights were designed to
      give three different light exposures: (i) white/blue strong light of 745 lux,
      6000 K; (ii) weak yellow light of 650 lux, 4000 K; and (iii) yellow moderate
      light of 700 lux, 4000 K. In a crossover design, the normal and new light
      exposures were given during a sequence of three night shifts, two free days, two
      morning shifts, and one afternoon shift (NNN + MMA), with 7 wks between sessions.
      The operators consisted of two groups; seven reactor operators from seven work
      teams were at one time exposed to the new equipment and 16 other operators were
      used as controls. The study was conducted during winter with reduced
      opportunities of daylight exposure during work, after night work, or before
      morning work. Operators wore actigraphs, filled in a sleep/wake diary, including
      ratings of sleepiness on the Karolinska Sleepiness Scale (KSS) every 2 h, and
      provided saliva samples for analysis of melatonin at work (every 2nd h during one
      night shift and first 3 h during one morning shift). Results from the wake/sleep
      diary showed the new light treatment increased alertness during the 2nd night
      shift (interaction group * light * time, p < .01). Time of waking was delayed in
      the light condition after the 3rd night shift (group * light, p < .05), but the
      amount of wake time during the sleep span increased after the 2nd night shift (p
      < .05), also showing a tendency to affect sleep efficiency (p < .10). Effects on
      circadian phase were difficult to establish given the small sample size and
      infrequent sampling of saliva melatonin. Nonetheless, it seems that appropriate
      dynamic light in rooms without windows during the dark Nordic season may promote
      alertness, sleep, and better adaptation to quickly rotating shiftwork.

PMID- 22621363
TI  - Digital image analysis vs. clinical assessment to evaluate repigmentation after
      punch grafting in vitiligo.
AB  - BACKGROUND: Repigmentation as a treatment outcome in vitiligo is not assessed in
      a standard way, making results of clinical trials hard to compare. Different
      types of repigmentation assessments after punch grafting have not been compared
      so far. OBJECTIVE: To compare assessments of repigmentation by a digital image
      analysis system (DIAS) with those of clinical observers and patients after punch
      grafting for vitiligo. METHODS: One vitiligo patch was selected in each patient
      (n = 21). This patch was treated with the punch grafting technique. The grade of
      repigmentation (%) after 3 months was assessed by: (i) DIAS; (ii) 3 clinical
      observers ; and (iii) the patient, scoring the grade of repigmentation on
      photographs. Physicians and patients also evaluated the global result on a 7
      point scale. RESULTS: There was an almost perfect agreement between the three
      clinical observers and the DIAS (ICC 0.83). As expected, variation was found
      between the clinical observers. Patients' scores showed a moderate agreement with
      the DIAS (ICC 0.49) and a poor agreement with the physicians (ICC 0.28). Overall,
      the patients were more satisfied with the results than the physicians.
      CONCLUSIONS: Whereas the results of the digital and clinical assessments were
      comparable, patients' ratings diverged. The DIAS can overcome the inevitable
      differences between observers, which are intrinsic to a visual grading method,
      and is advisable for clinical trials on vitiligo to objectively assess
      repigmentation in limited lesions.

PMID- 22621364
TI  - Concrete problems in the abstract deontic selection task - and how to solve them.
AB  - The abstract deontic selection task was introduced by Cheng and Holyoak with the
      aim of demonstrating that people possess abstract reasoning schemas for
      processing deontic rules about what an individual must, must not, may, or need
      not do. Solving this task requires people to detect possible rule violators. The
      average solution rate across several studies, while being substantially higher
      than that with abstract nondeontic tasks, did not reach the level obtained with
      concrete deontic tasks. A task analysis based on the deontic principles by Beller
      uncovers several problems with the formulation of the original task. They concern
      the presentation of the deontic rule as well as the instructions (focusing on
      rule following) and result in a specific selection behaviour. Three experiments
      replicate the difficulties with the original task and show that task performance
      increases when the formulation problems are resolved. The best performance was
      obtained with a task that combined a genuine violation detection instruction with
      a genuine permission rule. Interestingly, permissions are weak deontic rules
      that, if taken literally, cannot be violated in a deontic sense. Therefore,
      people must interpret these rules as implying a strong deontic constraint (i.e.,
      a ban), which then constitutes the basis for solving the task. The results
      provide novel insights into the interpretation of deontic rules and into the role
      that these content-specific, but abstract, tasks can play for the study of
      reasoning processes.

PMID- 22621365
TI  - Endovascular aneurysm repair: a perioperative perspective.
AB  - Endovascular aneurysm repair (EVAR), has surpassed open repair as the technique
      of choice in many centres in response to several large studies which showed
      significantly improved 30-day mortality. While several multicentre EVAR trials
      looked at surgical outcomes, very few have specifically investigated the effect
      of anaesthetic techniques or perioperative care of these patients. The purpose of
      this review to is to present some of the current evidence for the different
      aspects of perioperative management of patients undergoing EVAR. This includes
      surgical considerations, pre-operative assessment, and choice of anaesthetic
      technique as well as pharmacological protective strategies.

PMID- 22621366
TI  - Association of epidermal growth factor +61 A/G polymorphism in Chinese patients
      with colon cancer.
AB  - Epidermal growth factor (EGF) plays an important role in tumorigenesis. The
      association between the +61 A/G polymorphism of the EGF gene and colon cancer
      risk remains controversial and unclear. The objective of this study was to
      investigate the association between EGF +61 A/G polymorphism and colon cancer
      risk in a Chinese population. A hospital-based case-control study was conducted
      to assess the possible association between EGF +61 A/G polymorphism and colon
      cancer risk. A total of 180 colon cancer patients and 180 cancer-free healthy
      controls were recruited in the Chinese population. Genomic DNA was isolated from
      peripheral blood, and gene polymorphisms were analyzed by polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP). Colon cancer
      patients had a significantly higher frequency of +61 GG genotype (odds ratio
      [OR]=1.93, 95% confidence interval [CI]=1.07, 3.50; p=0.03) than that of
      controls. When stratified by the tumor location, tumor size, growth pattern,
      differentiation, and tumor-node-metastasis (TNM) stage of colon cancer, no
      statistically significant results were observed. Our study revealed that EGF +61
      GG genotype was associated with a higher risk of colon cancer in Chinese
      population.

PMID- 22621367
TI  - Low-temperature threshold for egg survival of a post-diapause and non-diapause
      European aedine strain, Aedes albopictus (Diptera: Culicidae).
AB  - BACKGROUND: The interplay between global warming and invasive arthropods in
      temperate zones is of utmost interest in terms of the potential expansions of
      vector-borne diseases. Up to now, investigations on the recent establishment of
      mosquito vectors have focused on temperatures during their phases of activity.
      However, cold temperatures may also act as a strong ecological constraint.
      Projected changes in winter climate indicate an increase of mean minimum
      temperatures of the coldest quarter, less frequent days with frost and a shorter
      frost-season in Europe at the end of the century. Nevertheless, single cold
      extremes are also expected to persist under warming scenarios, which have a
      strong impact on reproduction success. METHODS: Here, the temperature constraints
      of European Aedes albopictus eggs, which had passed through a diapause, compared
      to non-diapausing eggs were examined systematically under controlled laboratory
      conditions. Additionally, one tropical strain of Ae. albopictus and of Ae.
      aegypti was used in the comparison. RESULTS: The lower temperature threshold
      tolerated by the European eggs of Ae. albopictus which have undergone a diapause,
      was -10 degrees C for long term exposures (12 and 24h) and -12 degrees C for 1h
      exposure. Non-diapausing eggs of European Ae. albopictus were found to hatch
      after a -7 degrees C cold treatment (8, 12 and 24h exposure). Both tropical
      aedine species only tolerated the long term treatment at -2 degrees C. Neither
      Ae. albopictus nor Ae. aegypti eggs hatched after being exposed to -15 degrees C.
      Survival was mainly influenced by temperature (F = 329.2, df = 1, p < 0.001),
      whereas the duration of the cold treatment only significantly influenced the
      hatching response at the thermal limits of survival (F = 5.6, df = 1, p = 0.031)
      but not at 0 degrees C (F = 0.1, df = 1, p = 0.730). Hatching success after the
      cold treatment was significantly increased in European eggs, which have undergone
      a diapause compared to non-diapausing eggs (F = 14.7, df = 3, p < 0.001). These
      results illustrate rapid adaptation. CONCLUSIONS: Here, low temperature
      thresholds for aedine mosquito egg survival were detected. The compilation of
      risk maps for temperate regions can substantially be improved by considering
      areas where an establishment of a vector population is unlikely due to winter
      conditions.

PMID- 22621368
TI  - Safety of local anesthetics administered intrathecally in diabetic rats.
AB  - OBJECTIVES: Although retrospective studies show the risk of neurological
      complications after spinal anesthesia with local anesthetics is small in diabetic
      patients, there is still concern about the safety of different local anesthetics
      in diabetics undergoing neuroaxial anesthesia. We examined block duration and
      histology of spinal cord and roots with intrathecal local anesthetics in diabetic
      rats. METHODS: Rats were made diabetic with streptozotocin injection. Blood
      glucose levels confirmed diabetes, and diabetic neuropathy was verified by
      tactile hypersensitivity. Diabetic and nondiabetic rats received four intrathecal
      injections at 3-4-day intervals of 0.75% bupivacaine, with/without 100 ug/mL
      epinephrine; and 2% lidocaine, with/without 100 ug/mL epinephrine, and duration
      of sensory (pinprick) and motor (toe-spreading reflex) response inhibition
      recorded. Four days after the last drug injection, histology of spinal cord and
      roots was performed. RESULTS: All streptozotocin rats became diabetic and had
      pronounced tactile allodynia. Intrathecal injection of local anesthetics showed
      longer duration of sensory and motor block in diabetic rats vs nondiabetics.
      Histology of caudal spinal cord showed no difference in neuropathology between
      diabetic and nondiabetic rats. Necrotic neurons were not seen in either group,
      and white-matter pathology involved less than 0.1% of fibers. Histology of the
      spinal roots also showed no difference in pathology between groups, and pathology
      involved less than 0.1% of fibers. Neuron somas in the dorsal root ganglia were
      normal. CONCLUSIONS: Duration of local anesthetic spinal block is longer in
      diabetic animals than in nondiabetics. However, there was no increased pathology
      of spinal cord, roots, or dorsal root ganglia.

PMID- 22621369
TI  - Modeling detergent organization around aquaporin-0 using small-angle X-ray
      scattering.
AB  - Solubilization of integral membrane proteins in aqueous solutions requires the
      presence of amphiphilic molecules like detergents. The transmembrane region of
      the proteins is then surrounded by a corona formed by these molecules, ensuring a
      hydrophilic outer surface. The presence of this corona has strongly hampered
      structural studies of solubilized membrane proteins by small-angle X-ray
      scattering (SAXS), a technique frequently used to monitor conformational changes
      of soluble proteins. Through the online combination of size exclusion
      chromatography, SAXS, and refractometry, we have determined a precise geometrical
      model of the n-dodecyl beta-d-maltopyranoside corona surrounding aquaporin-0, the
      most abundant membrane protein of the eye lens. The SAXS data were well-fitted by
      a detergent corona shaped in an elliptical toroid around the crystal structure of
      the protein, similar to the elliptical shape recently reported for nanodiscs
      (Skar-Gislinge et al. J. Am. Chem. Soc. 2010, 132, 13713-13722). The torus
      thickness determined from the curve-fitting protocol is in excellent agreement
      with the thickness of a lipid bilayer, while the number of detergent molecules
      deduced from the volume of the torus compares well with those obtained on the
      same sample from refractometry and mass analysis based on SAXS forward
      scattering. For the first time, the partial specific volume of the detergent
      surrounding a protein was measured. The present protocol is a crucial step toward
      future conformational studies of membrane proteins in solution.

PMID- 22621370
TI  - Neurotrophic actions initiated by proNGF in adult sensory neurons may require
      peri-somatic glia to drive local cleavage to NGF.
AB  - The nerve growth factor (NGF) precursor, proNGF, is implicated in various
      neuropathological states. ProNGF signals apoptosis by forming a complex with the
      receptors p75 and sortilin, however, it can also induce neurite growth, proposed
      to be mediated by the receptor of mature NGF, tyrosine kinase receptor A (TrkA).
      The way in which these dual effects occur in adult neurons is unclear. We
      investigated the neurotrophic effects of proNGF on peptidergic sensory neurons
      isolated from adult mouse dorsal root ganglia and found that proNGF stimulated
      neurite extension and branching, requiring p75, sortilin and TrkA. Neurite growth
      rarely occurred in sortilin-expressing neurons but was commonly observed in TrkA
      positive, sortilin-negative neurons that associated closely with sortilin
      positive glia. ProNGF was unable to induce local trophic effects at growth cones
      where sortilin-positive glia was absent. We propose that in adult sensory neurons
      the neurotrophic response to proNGF is mediated by NGF and TrkA, and that peri
      somatic glia may participate in sortilin- and p-75 dependent cleavage of proNGF.
      The potential ability of local glial cells to provide a targeted supply of NGF
      may provide an important way to promote trophic (rather than apoptotic) outcomes
      under conditions where regeneration or sprouting is required.

PMID- 22621371
TI  - Comparing thousands of circular genomes using the CGView Comparison Tool.
AB  - BACKGROUND: Continued sequencing efforts coupled with advances in sequencing
      technology will lead to the completion of a vast number of small genomes. Whole
      genome comparisons represent an important part of the analysis of any new genome
      sequence, as they can provide a better understanding of the biology and evolution
      of the source organism. Visualization of the results is important, as it allows
      information from a variety of sources to be integrated and interpreted. However,
      existing graphical comparison tools lack features needed for efficiently
      comparing a new genome to hundreds or thousands of existing sequences. Moreover,
      existing tools are limited in terms of the types of comparisons that can be
      performed, the extent to which the output can be customized, and the ease with
      which the entire process can be automated. RESULTS: The CGView Comparison Tool
      (CCT) is a package for visually comparing bacterial, plasmid, chloroplast, or
      mitochondrial sequences of interest to existing genomes or sequence collections.
      The comparisons are conducted using BLAST, and the BLAST results are presented in
      the form of graphical maps that can also show sequence features, gene and protein
      names, COG (Clusters of Orthologous Groups of proteins) category assignments, and
      sequence composition characteristics. CCT can generate maps in a variety of
      sizes, including 400 Megapixel maps suitable for posters. Comparisons can be
      conducted within a particular species or genus, or all available genomes can be
      used. The entire map creation process, from downloading sequences to redrawing
      zoomed maps, can be completed easily using scripts included with the CCT. User
      defined features or analysis results can be included on maps, and maps can be
      extensively customized. To simplify program setup, a CCT virtual machine that
      includes all dependencies preinstalled is available. Detailed tutorials
      illustrating the use of CCT are included with the CCT documentation. CONCLUSION:
      CCT can be used to visually compare a reference sequence to thousands of existing
      genomes or sequence collections (next-generation sequencing reads for example) on
      a standard desktop computer. It provides analysis and visualization functionality
      not available in any existing circular genome visualization tool. By visually
      presenting sequence conservation information along with functional
      classifications and sequence composition characteristics, CCT can be a useful
      tool for identifying rapidly evolving or novel sequences, horizontally
      transferred sequences, or unusual functional properties in newly sequenced
      genomes. CCT is freely available for download at
      http://stothard.afns.ualberta.ca/downloads/CCT/.

PMID- 22621372
TI  - Stereoselective synthesis of norephedrine and norpseudoephedrine by using
      asymmetric transfer hydrogenation accompanied by dynamic kinetic resolution.
AB  - Each of the enantiomers of both norephedrine and norpseudoephedrine were
      stereoselectively prepared from the common, prochiral cyclic sulfamidate imine of
      racemic 1-hydroxy-1-phenyl-propan-2-one by employing asymmetric transfer
      hydrogenation (ATH) catalyzed by the well-defined chiral Rh-complexes, (S,S)- or
      (R,R)-Cp*RhCl(TsDPEN), and HCO(2)H/Et(3)N as the hydrogen source. The ATH
      processes are carried out under mild conditions (rt, 15 min) and are accompanied
      by dynamic kinetic resolution.

PMID- 22621373
TI  - CD44 enhances invasion of basal-like breast cancer cells by upregulating serine
      protease and collagen-degrading enzymatic expression and activity.
AB  - INTRODUCTION: Basal-like breast cancers (BL-BCa) have the worst prognosis of all
      subgroups of this disease. Hyaluronan (HA) and the HA receptor CD44 have a long
      standing association with cell invasion and metastasis of breast cancer. The
      purpose of this study was to establish the relation of CD44 to BL-BCa and to
      characterize how HA/CD44 signaling promotes a protease-dependent invasion of
      breast cancer (BrCa) cells. METHODS: CD44 expression was determined with
      immunohistochemistry (IHC) analysis of a breast cancer tissue microarray (TMA).
      In vitro experiments were performed on a panel of invasive BL-BCa cell lines, by
      using quantitative polymerase chain reaction (PCR), immunoblotting, protease
      activity assays, and invasion assays to characterize the basis of HA-induced,
      CD44-mediated invasion. RESULTS: Expression of the hyaluronan (HA) receptor CD44
      associated with the basal-like subgroup in a cohort of 141 breast tumor specimens
      (P = 0.018). Highly invasive cells of the representative BL-BCa cell line, MDA-MB
      231 (MDA-MB-231Hi) exhibited increased invasion through a basement membrane
      matrix (Matrigel) and collagen. In further experiments, HA-induced promotion of
      CD44 signaling potentiated expression of urokinase plasminogen activator (uPA)
      and its receptor uPAR, and underpinned an increased cell-associated activity of
      this serine protease in MDA-MB-231Hi and a further BL-BCa cell line, Hs578T
      cells. Knockdown of CD44 attenuated both basal and HA-stimulated uPA and uPAR
      gene expression and uPA activity. Inhibition of uPA activity by using (a) a gene
      targeted RNAi or (b) a small-molecule inhibitor of uPA attenuated HA-induced
      invasion of MDA-MB-231Hi cells through Matrigel. HA/CD44 signaling also was shown
      to increase invasion of MDA-MB-231 cells through collagen and to potentiate the
      collagen-degrading activity of MDA-MB-231Hi cells. CD44 signaling was
      subsequently shown to upregulate expression of two potent collagen-degrading
      enzymes, the cysteine protease cathepsin K and the matrix metalloprotease MT1
      MMP. RNAi- or shRNA-mediated depletion of CD44 in MDA-MB-231Hi cells decreased
      basal and HA-induced cathepsin K and MT1-MMP expression, reduced the collagen
      degrading activity of the cell, and attenuated cell invasion through collagen.
      Pharmacologic inhibition of cathepsin K or RNAi-mediated depletion of MT1-MMP
      also attenuated MDA-MB-231Hi cell invasion through collagen. CONCLUSION: HA
      induced CD44 signaling increases a diverse spectrum of protease activity to
      facilitate the invasion associated with BL-BCa cells, providing new insights into
      the molecular basis of CD44-promoted invasion.

PMID- 22621375
TI  - Factors influencing the specificity of inhibitor binding to the human and malaria
      parasite dihydroorotate dehydrogenases.
AB  - The de novo pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase is an
      emerging drug target for the treatment of malaria. In this context a key property
      of Plasmodium falciparum DHODH (PfDHODH) is that it can be selectively inhibited
      over its human homologue (HsDHODH). However, HsDHODH is also a validated drug
      target for autoimmune diseases such as arthritis. Here a series of novel
      inhibitors is described that includes compounds that switch specificity between
      the two enzymes as a result of small alterations in chemical structure. Structure
      activity relationship (SAR), crystallography, docking, and mutagenesis studies
      are used to examine the binding modes of the compounds within the two enzymes and
      to reveal structural changes induced by inhibitor binding. Within this series,
      compounds with therapeutically relevant HsDHODH activity are described and their
      binding modes characterized using X-ray crystallography, which reveals a novel
      conformational shift within the inhibitor binding site.

PMID- 22621374
TI  - Charged nanomatrices as efficient platforms for modulating cell adhesion and
      shape.
AB  - In this article, we describe the design and manipulation of charged nanomatrices
      and their application as efficient platforms for modulating cell behaviors. Using
      electrospraying technology and well designed biomaterials, poly(E-caprolactone;
      PCL) and polyethylenimine, the negatively charged PCL nanomatrix (nPCL
      nanomatrix) and the positively charged PCL nanomatrix (pPCL nanomatrix) were
      fabricated. It was demonstrated that cell adhesion, affinity, and shape were
      sensitively modulated in negatively and positively charged nanomatrices. Our
      results showed that the pPCL nanomatrix promoted adhesion of NIH 3T3 fibroblast
      cells as compared to the nPCL nanomatrix. When fluid shear stress was applied,
      cell affinity on the pPCL nanomatrix increased even more. NIH 3T3 fibroblast
      cells adopted a relatively spherical shape on the pPCL nanomatrix while adopting
      an aligned, narrow shape on the nPCL nanomatrix. It was also found that charged
      nanomatrices influenced the cross-sectional cell shape. The cross-sectional cell
      shape on the pPCL nanomatrix was extremely flattened, whereas the cross-sectional
      cell shape was relatively round on the nPCL nanomatrix and some of the adhered
      cells floated. We also showed that the surfaces of the nPCL and pPCL nanomatrices
      adsorbed the different serum proteins. These results collectively demonstrated a
      combination of environmental factors including nanoscale structure, electrostatic
      forces, and absorption of biomolecules on charged substrates affected cell
      response in terms of cellular adhesion and shape.

PMID- 22621377
TI  - Germline transformation of the diamondback moth, Plutella xylostella L., using
      the piggyBac transposable element.
AB  - The diamondback moth, Plutella xylostella, is one of the most economically
      important agricultural pests. The larvae of this moth cause damage by feeding on
      the foliage of cruciferous vegetables such as cabbage, broccoli, cauliflower and
      rapeseed. Control generally comprises chemical treatment; however, the
      diamondback moth is renowned for rapid development of resistance to pesticides.
      Other methods, such as biological control, have not been able to provide adequate
      protection. Germline transformation of pest insects has become available in
      recent years as an enabling technology for new genetics-based control methods,
      such as the Release of Insects carrying a Dominant Lethal (RIDL((r)) ). In the
      present study, we report the first transformation of the diamondback moth, using
      the piggyBac transposable element, by embryo microinjection. In generating
      transgenic strains using four different constructs, the function of three
      regulatory sequences in this moth was demonstrated in driving expression of
      fluorescent proteins. The transformation rates achieved, 0.48-0.68%, are
      relatively low compared with those described in other Lepidoptera, but not
      prohibitive, and are likely to increase with experience. We anticipate that
      germline transformation of the diamondback moth will permit the development of
      RIDL strains for use against this pest and facilitate the wider use of this
      species as a model organism for basic studies.

PMID- 22621376
TI  - Feasibility and effectiveness of a targeted diabetes prevention program for 18 to
      60-year-old South Asian migrants: design and methods of the DH!AAN study.
AB  - BACKGROUND: South Asian migrants are at particularly high risk of type 2
      diabetes. Previous studies have shown that intensive lifestyle interventions may
      prevent the onset of diabetes. Such interventions have not been culturally
      adapted and evaluated among South Asians in industrialized countries. Therefore,
      we have set up a randomized controlled trial to study the effectiveness of a
      targeted lifestyle intervention for the risk of type 2 diabetes and
      cardiovascular risk factors among 18 to 60-year-old Hindustani Surinamese (South
      Asians) in The Hague, the Netherlands. Here we present the study design and
      describe the characteristics of those recruited. METHODS: Between May 18, 2009
      and October 11, 2010, we screened 2307 Hindustani Surinamese (18-60 years old)
      living in The Hague. We sent invitations to participate to those who had an
      impaired fasting glucose of 5.6-6.9 mmol/l, an impaired glucose tolerance of 7.8
      11.0 mmol/L, a glycated hemoglobin level of 6.0% or more and/or a value of 2.39
      or more for the homeostasis model assessment of estimated insulin resistance. In
      total, 536 people (56.1% of those eligible) participated. People with a higher
      level of education and a family history of type 2 diabetes were more likely to
      participate. The control and intervention groups were similar with regard to
      important background characteristics. The intervention group will receive a
      culturally targeted intervention consisting of dietary counseling using
      motivational interviewing and a supervised physical activity program. The control
      group will receive generic lifestyle advice. To determine the effectiveness, a
      physical examination (anthropometrics, cardiorespiratory test, lipid profile, and
      measures of oral glucose tolerance, glycated hemoglobin, and insulin) and
      interview (physical activity, diet, quality of life, and intermediate outcomes)
      were carried out at baseline and will be repeated at 1 year and 2 years. The
      process and the costs will be evaluated. DISCUSSION: This trial will provide
      insight into the feasibility and effectiveness of a targeted, intensive,
      lifestyle intervention for the risk of type 2 diabetes and cardiovascular risk
      factors among 18 to 60-year-old South Asians. TRIAL REGISTRATION: Dutch Trial
      Register: NTR1499.

PMID- 22621378
TI  - Effect of adjuvants on the humoral immune response to congopain in mice and
      cattle.
AB  - BACKGROUND: We investigated several adjuvants for their effects on the humoral
      immune response in both mice and cattle using the central domain of congopain
      (C2), the major cysteine protease of Trypanosoma congolense, as a model for
      developing a vaccine against animal trypanosomosis. The magnitude and
      sustainability of the immune response against C2 and the occurrence of a booster
      effect of infection, an indirect measure of the presence of memory cells, were
      determined by ELISA, while spectrofluorometry was used to determine and measure
      the presence of enzyme-inhibiting antibodies. RESULTS: Mice immunized with
      recombinant C2 in TiterMaxTM, AdjuphosTM, purified saponin Quil ATM or GerbuTM
      showed the best response according to the evaluation criteria and the latter
      three were chosen for the cattle vaccination study. The cattle were challenged
      with T. congolense four and a half months after the last booster. Cattle
      immunized with recombinant C2 in purified saponin Quil ATM showed the best
      antibody response according to the measured parameters. CONCLUSIONS: We
      identified purified saponin Quil ATM as a good adjuvant for immunizations with
      C2. The results from this study will be useful in future attempts to develop an
      effective anti-disease vaccine against African trypanosomosis.

PMID- 22621379
TI  - Identifying the molecular mechanics and binding dynamics characteristics of
      potent inhibitors to HIV-1 protease.
AB  - Human immunodeficiency virus type 1 protease (HIV-1 PR) is one of the primary
      inhibition targets for chemotherapy of AIDS because of its critical role in the
      replication cycle of the HIV. In this work, a combinatory coarse-grained and
      atomistic simulation method was developed for dissecting molecular mechanisms and
      binding process of inhibitors to the active site of HIV-1 PR, in which 35 typical
      inhibitors were trialed. We found that the molecular size and stiffness of the
      inhibitors and the binding energy between the inhibitors and PR play important
      roles in regulating the binding process. Comparatively, the smaller and more
      flexible inhibitors have larger binding energy and higher binding rates; they
      even bind into PR without opening the flaps. In contrast, the larger and stiffer
      inhibitors have lower binding energy and lower binding rate, and their binding is
      subjected to the opening and gating of the PR flaps. Furthermore, the components
      of binding free energy were quantified and analyzed by their dependence on the
      molecular size, structures, and hydrogen bond networks of inhibitors. Our results
      also deduce significant dynamics descriptors for determining the quantitative
      structure and property relationship in potent drug ligands for HIV-1 PR
      inhibition.

PMID- 22621380
TI  - Combined renin angiotensin blockade in childhood steroid-resistant nephrotic
      syndrome.
AB  - BACKGROUND: Reduced proteinuria results in delayed deterioration of renal
      function and remission of proteinuria predicts a good long-term prognosis in
      steroid-resistant nephrotic syndrome (SRNS). The aim of this study was to analyze
      the effects of the combined angiotensin-converting enzyme inhibitor and
      angiotensin II receptor blocker in reducing proteinuria in SRNS. METHODS: A
      prospective study of eight patients with SRNS was conducted at the Department of
      Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University from
      September 2003 to December 2007. Enalapril was given at 0.1 mg/kg/day and was
      increased by 0.1 mg/kg/day every 4 weeks up to 0.6 mg/kg/day (maximum 40 mg/day)
      and 1 mg/kg/day of losartan was added for 4 weeks and stepped up to 2 mg/kg/day
      (maximum 100 mg/day) for another 4 weeks. RESULTS: There were five boys (62.5%)
      and three girls (37.5%). The mean age at diagnosis was 8.3 +/- 4.1 years (range
      2.05-13 years) and age at enrollment was 11.7 +/- 3.8 years (range 6-16 years).
      Renal histology revealed seven focal segmental glomerulosclerosis and one
      immunoglobulin M nephropathy. The results showed significant reduction on mean
      spot urine protein : creatinine ratio from 9.6 +/- 2.3 to 3.6 +/- 1.6 (P < 0.05)
      and 24-h urine protein from 182.8 +/- 59.6 to 28.7 +/- 8.2 mg/m(2) /h (P < 0.05).
      Urine protein reduction ratio at the end of the study was 50% (P= 0.08). Serum
      cholesterol, albumin, potassium, blood pressure and renal function had no
      significant change. No clinical and laboratory side-effects were reported.
      CONCLUSION: Combined high-dose angiotensin II receptor blocker to high-dose
      angiotensin-converting enzyme inhibitor therapy is safe and effective in reducing
      proteinuria in childhood SRNS. However a large-scale study should be conducted to
      validate this result.

PMID- 22621381
TI  - The feasibility, safety and outcomes of laparoscopic re-operation for achalasia.
AB  - INTRODUCTION: Heller myotomy for achalasia is associated with a recurrence rate
      of around 10%, thus reoperative surgery is often necessitated. This paper aims to
      review the available literature on laparoscopic reoperation for achalasia in
      order to assess its feasibility and effectiveness. MATERIAL & METHODS: A Medline,
      Embase, Ovid, Cochrane database and Google(TM) Scholar search was performed with
      the following Mesh terms: "laparoscopic", "redo", "reoperative", "Heller's",
      "esophagomyotomy" and "achalasia". Outcomes of interest included patient
      demographics and details of primary procedure, operative details, intra- and post
      operative complications and symptom scores. RESULTS: Seven studies reported
      outcomes from 54 cases. Conversion occurred in 7% (4/54) of cases. Thirteen
      percent (7/54) of patients sustained intra-operative gastric or oesophageal
      perforation; however these were all noted and repaired intra-operatively leading
      to no subsequent morbidity. No deaths were reported. Pre- and post operative
      symptom scores were heterogeneous, however did appear to improve after the
      procedure. DISCUSSION: This review demonstrates that laparoscopic reoperation for
      achalasia is feasible and safe with complication rates comparable to the primary
      laparoscopic operation. It is recommended that laparoscopic reoperative Heller's
      myotomy should only be performed by surgeons with special interest in
      oesophagogastric surgery and adequate experience in laparoscopic surgery for
      achalasia.

PMID- 22621382
TI  - Base-free dehydrogenative coupling of enolizable carbonyl compounds with silanes.
AB  - A dehydrogenative coupling between enolizable carbonyl compounds and equimolar
      amounts of triorganosilanes catalyzed by a tethered ruthenium complex with a Ru-S
      bond is reported. The complex is assumed to fulfill a dual role by activating the
      Si-H bond to release a silicon electrophile and by abstracting an alpha-proton
      from the intermediate silylcarboxonium ion, only liberating dihydrogen as the
      sole byproduct. Reaction rates are exceedingly high at room temperature with very
      low loadings of the ruthenium catalyst.

PMID- 22621383
TI  - Chitosan/siRNA nanoparticles encapsulated in PLGA nanofibers for siRNA delivery.
AB  - Composite nanofibers of biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA)
      encapsulating chitosan/siRNA nanoparticles (NPs) were prepared by
      electrospinning. Acidic/alkaline hydrolysis and a bulk/surface degradation
      mechanism were investigated in order to achieve an optimized release profile for
      prolonged and efficient gene silencing. Thermo-controlled AFM in situ imaging not
      only revealed the integrity of the encapsulated chitosan/siRNA polyplex but also
      shed light on the decreasing T(g) of PLGA on the fiber surfaces during release. A
      triphasic release profile based on bulk erosion was obtained at pH 7.4, while a
      triphasic release profile involving both surface erosion and bulk erosion was
      obtained at pH 5.5. A short alkaline pretreatment provided a homogeneous
      hydrolysis and consequently a nearly zero-order release profile. The interesting
      release profile was further investigated for siRNA transfection, where the
      encapsulated chitosan/siRNA NPs exhibited up to 50% EGFP gene silencing activity
      after 48 h post-transfection on H1299 cells.

PMID- 22621384
TI  - Solid-state synthesis of molybdenum and tungsten porphyrins and aerial oxidation
      of coordinated benzenethiolate to benzenesulfonate.
AB  - A new route is developed for the synthesis of molybdenum and tungsten porphyrins
      using [M(NO)(2)py(2)Cl(2)] (M = Mo, W) as the metal source and TPP (dianion of
      5,10,15,20-meso-tetraphenylporphyrin) in the benzoic acid melt. Complexes
      [Mo(V)O(TPP)(OOCPh)] (1) and [W(V)O(TPP)(OOCPh)] (2) are isolated in almost
      quantitative yield. These are characterized by single-crystal X-ray structure
      analysis, electron paramagnetic resonance, electronic and IR spectroscopy, and
      magnetic moment measurements. Benzenethiol substitutes for PhCOO(-) in 1, forming
      an intermediate thiolato complex that responds to the intramolecular redox
      reaction across the Mo(V)-SPh bond to yield [Mo(IV)O(TPP)] (3). Under an excess
      of benzenethiol, PhS(-) is coordinated to the vacant site in 3, which under
      aerial oxidation is oxidized to benzenesulfonate to form [Mo(V)O(TPP)(O(3)SPh)]
      (4). 2 undergoes similar aerial oxidation chemistry albeit slowly.

PMID- 22621385
TI  - Permission to share biospecimens.

PMID- 22621386
TI  - HLA B27 subtype distribution among patients with ankylosing spondylitis in
      eastern Turkey.
AB  - Human leukocyte antigen (HLA) B27 has a strong association with ankylosing
      spondylitis (AS) and other spondyloarthropathies. More than 70 subtypes of HLA
      B27 have been described. The present study investigated B27 subtype distribution
      among B27-positive patients with AS classified according to the modified New York
      criteria and healthy controls. Sequence-specific primer polymerase chain reaction
      technique was used for B27 subtyping of 43 unrelated patients with AS and 39
      volunteer bone marrow donors. Among patients with AS, the male-female ratio was
      6.2 and the mean age was 30 years. No relationship was found between the B27
      subtypes and clinical and laboratory findings in patients with AS (p>0.05).
      Similarly, the frequencies of B27 subtypes did not significantly differ between
      patients and controls. In this study, B*2746, B*2749, and B*2767 subtypes were
      detected for the first time. Among B27 subtypes, the most common B27 alleles
      found in the patients and the controls were B*2702 and B*2705. In addition,
      B*2702 subtype was found predominantly in both patients (48.8%) and controls
      (46.2%). In conclusion, in addition to commonly encountered B*2702 and B*2705 HLA
      subtypes, a B*2749 subtype in a patient with AS and B*2746 as well as B*2767
      subtypes in controls were determined for the first time.

PMID- 22621387
TI  - Communicable diseases and governance: a tale of two regions.
AB  - Regional policies and programmes on communicable disease prevention and control
      are becoming an important component of global public health. In a comparative
      fashion, we examined the situation in the European and Southeast Asian contexts,
      with a focus on the underlying institutional and political backgrounds
      underpinning the regionalisation of planning and interventions. Our findings
      document the emergence of two distinctive models of regional integration. While
      in Europe there is a process of institutionalisation and centralisation, in
      Southeast Asia the landscape of regional cooperation is characterised by the
      proliferation of many provisional projects, based on loose agreements and a
      decentralised structure that emphasises the initiative and sense of ownership of
      member countries. These two approaches, we conclude, reflect wider differences of
      political culture between supranational integration in Europe and
      intergovernmental agreements in Southeast Asia.

PMID- 22621388
TI  - Plasma YKL-40: a potential biomarker for psoriatic arthritis?
AB  - BACKGROUND: Plasma YKL-40 is an inflammatory biomarker. No useful biomarker
      exists in patients with psoriasis or psoriatic arthritis. OBJECTIVE: To measure
      YKL-40 and high-sensitivity C-reactive protein (hs-CRP) in patients with
      psoriasis or psoriatic arthritis before and during treatment. METHODS: In 48
      patients with psoriasis, we measured YKL-40, hs-CRP and Psoriasis Area and
      Severity Index (PASI) at inclusion and in a subgroup of 14 patients, we repeated
      the measurements after four to six weeks of methotrexate treatment. In 42
      patients with psoriatic arthritis, we measured YKL-40 and hs-CRP at inclusion and
      during 48 weeks of adalimumab treatment. The patients with psoriatic arthritis
      were divided into responders and non-responders. RESULTS: In patients with
      psoriasis, the baseline median PASI score was 10.8 and baseline YKL-40 was 45
      MUg/L. Seventeen per cent had elevated plasma YKL-40 compared with healthy
      subjects. Baseline PASI and YKL-40 were not correlated (rho = 0.14, P = 0.347)
      and YKL-40 and hs-CRP remained unchanged after treatment. In patients with
      psoriatic arthritis, the median pretreatment YKL-40 was 112 MUg/L and 43% had
      elevated YKL-40. YKL-40 decreased in 33 patients who responded to adalimumab
      (from 112 MUg/L to 68 at 48 weeks, P = 0.007). Hs-CRP decreased (from 4.65 mg/L
      to 0.91, P = 0.013) in the responders. In the non-responders (n = 9), YKL-40 and
      hs-CRP remained unchanged. CONCLUSIONS: YKL-40 is elevated in many patients with
      psoriatic arthritis, but not in patients with psoriasis. YKL-40 decreased in
      patients with psoriatic arthritis who responded to treatment. YKL-40 may be a
      useful biomarker to monitor the effect of treatment with tumour necrosis factor
      alpha inhibitors in patients with psoriatic arthritis.

PMID- 22621389
TI  - Effects of jasmonic acid, branching and girdling on carbon and nitrogen transport
      in poplar.
AB  - * Here, we examined the impact of jasmonate (JA) treatment, branching and phloem
      girdling on 13C and 15N import, invertase activity and polyphenol accumulation in
      juvenile tissues of unbranched and branched hybrid poplar saplings (Populus nigra
      * P. deltoides). * The import of 13C to juvenile tissues was positively
      correlated with invertase activity at the treatment site and enhanced by JA. Both
      invertase activity and 13C import were greater in shorter, younger branches and
      smaller, younger leaves. By contrast, JA treatments, branching and girdling had
      little or no impact on 15N import. * In poplar saplings with multiple lateral
      branches, we observed almost no 13C movement from subtending source leaves into
      lateral branches above them, with or without JA treatment. The presence of
      potentially competing branches, treated with JA or not, girdled or not, had no
      impact on carbohydrate (CHO) import or polyphenol accumulation in target
      branches. * We conclude that poplar branches comprise modules that are relatively
      independent from each other and from the stem below in terms of CHO movement,
      carbon-based defence production and response to elicitors. By contrast, branches
      are closely linked modules in terms of nitrogen movement. This should produce
      trees that are highly heterogeneous in quality for herbivores.

PMID- 22621390
TI  - A novel PAX6 mutation in Chinese patients with severe congenital aniridia.
AB  - PURPOSE: We identified a novel mutation in Paired Box gene 6 (PAX6) and
      characterized its associated clinical features of severe ocular malformation in a
      Chinese family with congenital aniridia. METHODS: We studied two patients with
      aniridia from a Chinese family. All patients and noncarriers in this family
      underwent full ophthalmologic, general and urinary examinations. Total genomic
      DNA was isolated from peripheral blood of two aniridia patients. PAX6 levels were
      determined by PCR and its mutational status was determined by sequencing. Direct
      sequencing detected variations in PAX6. RESULTS: Patients had bilateral
      congenital nystagmus, anterior polar cataract, absence of iris tissue, and foveal
      hypoplasia with severely reduced visual acuity. A novel heterozygous PAX6
      mutation in exon 6 c.662G>A (p.W100X) was identified which created a premature
      termination codon. This observed sequence alteration was not found in 100 normal
      controls and has not been previously reported. CONCLUSIONS: We identified a novel
      PAX6 mutation in a family with severe ocular malformation. Our study expands the
      mutational spectrum of PAX6 and enriches our knowledge of the relationship
      between genotype and phenotype due to these mutations.

PMID- 22621391
TI  - Is spinal manipulation effective for pain? An overview of systematic reviews.
AB  - OBJECTIVE: This article is aimed at critically evaluating the evidence from
      systematic reviews (SRs) of spinal manipulation in patients with pain. DESIGN:
      The study was designed as a SR of SRs. METHODS: Four electronic databases were
      searched to identify all relevant articles of the effectiveness of spinal
      manipulation for pain. SRs were defined as articles employing a repeatable
      methods section. RESULTS: Twenty-two SRs relating to the following pain
      conditions: low back pain (N = 6), headache (N = 5), neck pain (N = 4), any
      medical problem (N = 1), carpal tunnel syndrome (N = 1), dysmenorrhea (N = 1),
      fibromyalgia (N = 1), lateral epicondylitis (N = 1), musculoskeletal conditions
      (N = 1) and nonspinal pain (N = 1), were included. Positive or, for multiple SR,
      unanimously positive conclusions were drawn for none of the conditions mentioned
      earlier. LIMITATION: Publication bias as a well-known phenomenon may have been
      inherited in this article. CONCLUSION: Collectively, these data fail to
      demonstrate that spinal manipulation is an effective intervention for pain
      management.

PMID- 22621392
TI  - Downregulation of gastrokine-1 in gastric cancer tissues and restoration of its
      expression induced gastric cancer cells to apoptosis.
AB  - BACKGROUND: Gastrokine-1 (GKN1), a secreted protein, is specifically expressed in
      gastric mucosa to protect and maintain the integrity of gastric epithelium. The
      present study investigated differential expression of GKN1 in normal,
      precancerous, and cancerous gastric tissues, and explored the biological
      functions of GKN1 protein in gastric cancer cells. METHODS: RT-PCR, Western blot,
      and immunohistochemistry were performed to detect GKN1 expression in normal,
      precancerous, cancerous gastric tissues and seven gastric cancer cell lines. Gene
      transfection was used to restore GKN1 expression in gastric cancer AGS cells.
      Phenotypic changes (i.e., cell viability, apoptosis, cell cycle modulation, and
      sensitivity of gastric cancer cells to fluorouracil (5-FU)) were assayed in the
      transfected cells. DNA microarrays were used to analyze expression changes of
      apoptosis-related genes. RESULTS: Significant downregulation or absence of GKN1
      expression in seven gastric cancer cell lines were detected and progressive
      decrease of GKN1 expression from normal mucosa, precancerous tissue, to cancer
      tissues was observed. Moreover, restoration of GKN1 expression suppressed gastric
      cancer cell viability and induced the cells to undergo apoptosis. GKN1 expression
      also enhanced tumor cell sensitivity to 5-FU treatment. Moreover, it was found
      that GKN1 expression in AGS cells modulated expression of 19 apoptosis-related
      genes. CONCLUSIONS: Expression of GKN1 is progressively lost from normal mucosa,
      precancerous to cancerous gastric tissues, while restoration of GKN1 expression
      induces gastric cancer cells to undergo apoptosis, and enhances sensitivity of
      gastric cancer cells to 5-FU-induced apoptosis.

PMID- 22621393
TI  - JMJD6 is a driver of cellular proliferation and motility and a marker of poor
      prognosis in breast cancer.
AB  - INTRODUCTION: We developed an analytic strategy that correlates gene expression
      and clinical outcomes as a means to identify novel candidate oncogenes operative
      in breast cancer. This analysis, followed by functional characterization,
      resulted in the identification of Jumonji Domain Containing 6 (JMJD6) protein as
      a novel driver of oncogenic properties in breast cancer. METHODS: Through
      microarray informatics, Cox proportional hazards regression was used to analyze
      the correlation between gene expression and distant metastasis-free survival
      (DMFS) of patients in 14 independent breast cancer cohorts. JMJD6 emerged as a
      top candidate gene robustly associated with poor patient survival.
      Immunohistochemistry, siRNA-mediated silencing, and forced overexpression of
      JMJD6 in cell-based assays elucidated molecular mechanisms of JMJD6 action in
      breast cancer progression and shed light on the clinical breast cancer subtypes
      relevant to JMJD6 action. RESULTS: JMJD6 was expressed at highest levels in
      tumors associated with worse outcomes, including ER- and basal-like, Claudin-low,
      Her2-enriched, and ER+ Luminal B tumors. High nuclear JMJD6 protein was
      associated with ER negativity, advanced grade, and poor differentiation in tissue
      microarrays. Separation of ER+/LN- patients that received endocrine monotherapy
      indicated that JMJD6 is predictive of poor outcome in treatment-specific
      subgroups. In breast cancer cell lines, loss of JMJD6 consistently resulted in
      suppressed proliferation but not apoptosis, whereas forced stable overexpression
      increased growth. In addition, knockdown of JMJD6 in invasive cell lines, such as
      MDA-MB231, decreased motility and invasion, whereas overexpression in MCF-7 cells
      slightly promoted motility but did not confer invasive growth. Microarray
      analysis showed that the most significant transcriptional changes occurred in
      cell-proliferation genes and genes of the TGF-beta tumor-suppressor pathway. High
      proliferation was characterized by constitutively high cyclin E protein levels.
      The inverse relation of JMJD6 expression with TGF-beta2 could be extrapolated to
      the breast cancer cohorts, suggesting that JMJD6 may affect similar pathways in
      primary breast cancer. CONCLUSIONS: JMJD6 is a novel biomarker of tumor
      aggressiveness with functional implications in breast cancer growth and
      migration.

PMID- 22621394
TI  - Evaluation of the future atherosclerotic heart disease with oxidative stress and
      carotid artery intima media thickness in gestational diabetes mellitus.
AB  - BACKGROUND AND OBJECTIVE: In this study our aim was to evaluate paraoxonase
      (PON1) activity and free sulfhydryl groups (-SH) as antioxidative parameters and
      lipid hydroperoxide (LOOH) as oxidative parameter in the serum of women with
      gestational diabetes mellitus (GDM) and determine their relation with the degree
      of subclinical atherosclerosis. MATERIAL AND METHODS: Serum samples from 39
      pregnant women complicated with GDM and 40 healthy pregnant women were collected
      for the analysis of oxidative markers. Common carotid artery intima media
      thickness (CIMT) was measured for both groups to assess future atherosclerotic
      heart disease risk. PON1 activity and -SH were measured spectrophotometrically.
      LOOH levels were measured by ferrous oxidation with a xylenol orange assay.
      RESULTS: CIMT and LOOH levels were significantly higher (p = 0.01, p < 0.001,
      respectively) in GDM group compared to controls, whereas PON1 and -SH levels were
      significantly lower (p < 0.001 for both). CIMT values were significantly
      correlated with body mass index (BMI), 50 g oral glucose tolerance test (OGTT),
      and mean arterial blood pressure (MABP) (p = 0.003, p = 0.02, and p = 0.03,
      respectively). However, there was no correlation between CIMT and oxidative
      markers. CONCLUSIONS: Increased levels of LOOH and decreased levels of PON1 and 
      SH showed disturbance of antioxidative mechanisms in GDM. These changes were
      associated with increased BMI and MABP which may be relevant to GDM
      pathophysiology. Furthermore, increased CIMT values in GDM compared to healthy
      controls designate increased risk of future atherosclerotic heart disease.

PMID- 22621395
TI  - Synthesis of a uranium(VI)-carbene: reductive formation of uranyl(V)-methanides,
      oxidative preparation of a [R2C?U?O]2+ analogue of the [O?U?O]2+ uranyl ion (R =
      Ph2PNSiMe3), and comparison of the nature of U(IV)?C, U(V)?C, and U(VI)?C double
      bonds.
AB  - We report attempts to prepare uranyl(VI)- and uranium(VI) carbenes utilizing
      deprotonation and oxidation strategies. Treatment of the uranyl(VI)-methanide
      complex [(BIPMH)UO(2)Cl(THF)] [1, BIPMH = HC(PPh(2)NSiMe(3))(2)] with benzyl
      sodium did not afford a uranyl(VI)-carbene via deprotonation. Instead, one
      electron reduction and isolation of di- and trinuclear [UO(2)(BIPMH)(MU-Cl)UO(MU
      O){BIPMH}] (2) and [UO(MU-O)(BIPMH)(MU(3)-Cl){UO(MU-O)(BIPMH)}(2)] (3),
      respectively, with concomitant elimination of dibenzyl, was observed. Complexes 2
      and 3 represent the first examples of organometallic uranyl(V), and 3 is notable
      for exhibiting rare cation-cation interactions between uranyl(VI) and uranyl(V)
      groups. In contrast, two-electron oxidation of the uranium(IV)-carbene
      [(BIPM)UCl(3)Li(THF)(2)] (4) by 4-morpholine N-oxide afforded the first
      uranium(VI)-carbene [(BIPM)UOCl(2)] (6). Complex 6 exhibits a trans-CUO linkage
      that represents a [R(2)C?U?O](2+) analogue of the uranyl ion. Notably, treatment
      of 4 with other oxidants such as Me(3)NO, C(5)H(5)NO, and TEMPO afforded 1 as the
      only isolable product. Computational studies of 4, the uranium(V)-carbene
      [(BIPM)UCl(2)I] (5), and 6 reveal polarized covalent U?C double bonds in each
      case whose nature is significantly affected by the oxidation state of uranium.
      Natural Bond Order analyses indicate that upon oxidation from uranium(IV) to (V)
      to (VI) the uranium contribution to the U?C sigma-bond can increase from ca. 18
      to 32% and within this component the orbital composition is dominated by 5f
      character. For the corresponding U?C pi-components, the uranium contribution
      increases from ca. 18 to 26% but then decreases to ca. 24% and is again dominated
      by 5f contributions. The calculations suggest that as a function of increasing
      oxidation state of uranium the radial contraction of the valence 5f and 6d
      orbitals of uranium may outweigh the increased polarizing power of uranium in 6
      compared to 5.

PMID- 22621397
TI  - Irreversible protein kinase inhibitors: balancing the benefits and risks.

PMID- 22621399
TI  - Streamlining the medication process improves safety in the intensive care unit.
AB  - BACKGROUND: Multiple interventions were made to optimize the medication process
      in our intensive care unit (ICU). 1 Transcriptions from the medical order form to
      the administration plan were eliminated by merging both into a single document; 2
      the new form was built in a logical sequence and was highly structured to promote
      completeness and standardization of information; 3 frequently used drug names,
      approved units, and fixed routes were pre-printed; 4 physicians and nurses were
      trained with regard to the correct use of the new form. This study was aimed at
      evaluating the impact of these interventions on clinically significant types of
      medication errors. METHODS: Eight types of medication errors were measured by a
      prospective chart review before and after the interventions in the ICU of a
      public tertiary care hospital. We used an interrupted time-series design to
      control the secular trends. RESULTS: Over 85 days, 9298 lines of drug
      prescription and/or administration to 294 patients, corresponding to 754 patient
      days were collected and analysed for the three series before and three series
      following the intervention. Global error rate decreased from 4.95 to 2.14% (
      56.8%, P < 0.001). CONCLUSIONS: The safety of the medication process in our ICU
      was improved by simple and inexpensive interventions. In addition to the
      optimization of the prescription writing process, the documentation of
      intravenous preparation, and the scheduling of administration, the elimination of
      the transcription in combination with the training of users contributed to
      reducing errors and carried an interesting potential to increase safety.

PMID- 22621398
TI  - Dose-dependent changes in neuroinflammatory and arachidonic acid cascade markers
      with synaptic marker loss in rat lipopolysaccharide infusion model of
      neuroinflammation.
AB  - BACKGROUND: Neuroinflammation, caused by six days of intracerebroventricular
      infusion of bacterial lipopolysaccharide (LPS), stimulates rat brain arachidonic
      acid (AA) metabolism. The molecular changes associated with increased AA
      metabolism are not clear. We examined effects of a six-day infusion of a low-dose
      (0.5 ng/h) and a high-dose (250 ng/h) of LPS on neuroinflammatory, AA cascade,
      and pre- and post-synaptic markers in rat brain. We used artificial cerebrospinal
      fluid-infused brains as controls. RESULTS: Infusion of low- or high-dose LPS
      increased brain protein levels of TNFalpha, and iNOS, without significantly
      changing GFAP. High-dose LPS infusion upregulated brain protein and mRNA levels
      of AA cascade markers (cytosolic cPLA2-IVA, secretory sPLA2-V, cyclooxygenase-2
      and 5-lipoxygenase), and of transcription factor NF-kappaB p50 DNA binding
      activity. Both LPS doses increased cPLA2 and p38 mitogen-activated protein kinase
      levels, while reducing protein levels of the pre-synaptic marker, synaptophysin.
      Post-synaptic markers drebrin and PSD95 protein levels were decreased with high-
      but not low-dose LPS. CONCLUSIONS: Chronic LPS infusion has differential effects,
      depending on dose, on inflammatory, AA and synaptic markers in rat brain.
      Neuroinflammation associated with upregulated brain AA metabolism can lead to
      synaptic dysfunction.

PMID- 22621400
TI  - Increased hypoxia-inducible factor 1alpha expression in lung cells of horses with
      recurrent airway obstruction.
AB  - BACKGROUND: Recurrent airway obstruction (RAO, also known as equine heaves) is an
      inflammatory condition caused by exposure of susceptible horses to organic dusts
      in hay. The immunological processes responsible for the development and the
      persistence of airway inflammation are still largely unknown. Hypoxia-inducible
      factor (Hif) is mainly known as a major regulator of energy homeostasis and
      cellular adaptation to hypoxia. More recently however, Hif also emerged as an
      essential regulator of innate immune responses. Here, we aimed at investigating
      the potential involvement of Hif1-alpha in myeloid cells in horse with recurrent
      airway obstruction. RESULTS: In vitro, we observed that Hif is expressed in
      equine myeloid cells after hay dust stimulation and regulates genes such as tumor
      necrosis factor alpha (TNF-alpha), interleukin-8 (IL-8) and vascular endothelial
      growth factor A (VEGF-A). We further showed in vivo that airway challenge with
      hay dust upregulated Hif1-alpha mRNA expression in myeloid cells from the
      bronchoalveolar lavage fluid (BALF) of healthy and RAO-affected horses, with a
      more pronounced effect in cells from RAO-affected horses. Finally, Hif1-alpha
      mRNA expression in BALF cells from challenged horses correlated positively with
      lung dysfunction. CONCLUSION: Taken together, our results suggest an important
      role for Hif1-alpha in myeloid cells during hay dust-induced inflammation in
      horses with RAO. We therefore propose that future research aiming at functional
      inactivation of Hif1 in lung myeloid cells could open new therapeutic
      perspectives for RAO.

PMID- 22621401
TI  - Viral load at diagnosis and influenza A H1N1 (2009) disease severity in children.
AB  - To assess viral load at diagnosis (VLAD) as a biomarker of novel influenza
      disease severity, epidemiologic and clinical data of admitted patients <18 years
      old with Influenza A H1N1 (2009) infection and respiratory symptoms were
      prospectively collected in a single pediatric tertiary hospital, from weeks 30-51
      of 2009. Seventy patients were included. VLAD in children who had symptoms for >=
      5 days was an accurate parameter distinguishing the patients who required
      mechanical ventilation (MV) from those who did not required it (area under the
      ROC curve: 0.73; P=0.03). Having <4.5 log10 copies/ml with >= 5 days of symptoms
      was associated with a lower risk of requiring MV.

PMID- 22621403
TI  - Low-spin versus high-spin ground state in pseudo-octahedral iron complexes.
AB  - Pseudo-octahedral complexes of iron find applications as switches in molecular
      electronic devices, materials for data storage, and, more recently, as candidates
      for dye-sensitizers in dye-sensitized solar cells. Iron, as a first row
      transition metal, provides a weak ligand-field splitting in an octahedral
      environment. This results in the presence of low-lying (5)T excited states that,
      depending on the identity of iron ligands, can become the ground state of the
      complex. The small energy difference between the low-spin, (1)A, and high-spin,
      (5)T, states presents a challenge for accurate prediction of their ground state
      using density functional theory. In this work, we investigate the applicability
      of the B3LYP functional to the ground state determination of first row transition
      metal complexes, focusing mainly on Fe(II) polypyridine complexes with ligands of
      varying ligand field strength. It has been shown previously that B3LYP
      artificially favors the (5)T state as the ground state of Fe(II) complexes, and
      the error in the energy differences between the (1)A and (5)T states is
      systematic for a set of structurally related complexes. We demonstrate that
      structurally related complexes can be defined as pseudo-octahedral complexes that
      undergo similar distortion in the metal-ligand coordination environment between
      the high-spin and low-spin states. The systematic behavior of complexes with
      similar distortion can be exploited, and the ground state of an arbitrary Fe(II)
      complex can be determined by comparing the calculated energy differences between
      the singlet and quintet electronic states of a complex to the energy differences
      of structurally related complexes with a known, experimentally determined ground
      state.

PMID- 22621402
TI  - Prevalence of pathological internet use among adolescents in Europe: demographic
      and social factors.
AB  - AIMS: To investigate the prevalence of pathological internet use (PIU) and
      maladaptive internet use (MIU) among adolescents in 11 European countries in
      relation to demographic, social factors and internet accessibility. DESIGN: Cross
      sectional survey. SETTING: The 7th Framework European Union (EU) funded project,
      Saving and Empowering Young Lives in Europe (SEYLE), is a randomized controlled
      trial (RCT) evaluating interventions for risk behaviours among adolescents in
      Austria, Estonia, France, Germany, Hungary, Ireland, Israel, Italy, Romania,
      Slovenia and Spain, with Sweden serving as the coordinating centre. PARTICIPANTS:
      A total of 11 956 adolescents (female/male: 6731/5225; mean age: 14.9 +/- 0.89)
      recruited from randomly selected schools within the 11 study sites. MEASUREMENTS:
      Internet users were classified by gender into three categories: adaptive,
      maladaptive and pathological, based on their score in the Young Diagnostic
      Questionnaire for Internet Addiction (YDQ). FINDINGS: The overall prevalence of
      PIU was 4.4%; it was higher among males than females (5.2% versus 3.8%) and
      differed between countries (chi(2)  = 309.98; d.f. = 20; P < 0.001). PIU
      correlated significantly with mean hours online and male gender. The highest
      ranked online activities were watching videos, frequenting chatrooms and social
      networking; significantly higher rates of playing single-user games were found in
      males and social networking in females. Living in metropolitan areas was
      associated with PIU. Students not living with a biological parent, low parental
      involvement and parental unemployment showed the highest relative risks of both
      MIU and PIU. CONCLUSIONS: Across a range of countries in Europe, using the Young
      Diagnostic Questionnaire for Internet Addiction yields a prevalence of
      'pathological internet use' of 4.4% among adolescents, but varies by country and
      gender; adolescents lacking emotional and psychological support are at highest
      risk.

PMID- 22621404
TI  - Targeting Her-2+ breast cancer cells with bleomycin immunoliposomes linked to
      LLO.
AB  - Bleomycin is a membrane impermeable chemotherapeutic agent that is relatively
      innocuous extracellularly but highly cytotoxic when delivered directly to the
      cytoplasm. We report on the development of a liposome delivery system that
      targets Her-2 overexpressing breast cancer cells and breaches the endosomal
      barrier, delivering bleomycin to the cytoplasm. The liposomes are conjugated to
      the antibody trastuzumab, which results in specific binding and internalization
      of liposomes into Her-2 overexpressing cells. In addition, the liposomes are
      disulfide bonded to a pore-forming protein listeriolysin O (LLO) which forms
      pores in the endosome and allows the liposomal cargo to pass into the cytoplasm.
      We demonstrate specific delivery to Her-2 positive MCF-7/Her18 cells relative to
      Her-2 negative MCF-7 cells using a fluorescent probe calcein within the
      immunoliposomes. When calcein is replaced by bleomycin, the liposomes effectively
      reduce viability of five different Her-2 overexpressing cell lines (BT-474, SKBR
      3, MCF-7/Her18, HCC-1954 and MDA-453) while harming to a much lesser extent Her-2
      negative breast cell lines (MCF-7, MCF-12a and MCF-10a). The liposomes also
      affect trastuzumab-resistant cells, reducing MDA-453 cell number by 97% compared
      to untreated cells. Importantly, the concentration of drug needed to reduce tumor
      cell growth and viability using this liposome therapy is approximately 57,000
      fold less than the concentration needed if drug is delivered extracellularly,
      raising the possibility of increased therapeutic specificity with decreased side
      effects. 

PMID- 22621405
TI  - Total syntheses of graphisin A and sydowinin B.
AB  - Efficient syntheses of the highly substituted benzophenone graphisin A and the
      xanthone sydowinin B are described. Key steps involve aryl anion addition to
      substituted benzaldehyde derivatives, subsequent methyl ester installation, and
      dehydrative cyclization. Oxidation of graphisin A led to a spirodienone derived
      from a highly substituted benzoquinone intermediate.

PMID- 22621406
TI  - The effect of certain steroid hormones on the expression of genes involved in the
      metabolism of free radicals.
AB  - Steroid hormones influence the antioxidant processes of cells. However, the
      molecular mechanism of this effect is not fully clear. Our aim was to examine how
      steroid hormones affect the expression of certain genes that play a role in
      antioxidant processes. Blood was taken from ten healthy volunteers. Neutrophil
      granulocytes were separated and treated either with 17-beta-estradiol,
      progesterone, testosterone, or cortisol. Whole RNA was isolated and reverse
      transcription was carried out in treated and control groups. Relative
      quantification was performed with SYBR Green assay and gene-specific
      oligonucleotides. We found that the expression of Mn-superoxide dismutase was
      significantly increased by 17-beta-estradiol and testosterone, myeloperoxidase
      expression was significantly elevated by cortisol and progesterone, and the
      expression of NADPH oxidase was significantly decreased by progesterone. We
      conclude that the antioxidant effect of steroid hormones is in part carried out
      through transcriptional regulation of certain enzymes. Subsequent studies are
      required in order to examine the non-genomic, membrane receptor mediated effect
      of steroids on antioxidant processes.

PMID- 22621407
TI  - Health care workers in Africa access a broad range of topics using evidence-based
      online medical information.
AB  - Health care workers (HCW) rely on Internet-based medical resources to obtain
      current evidence-based clinical guidelines. While such resources are being used
      with increasing frequency in developed countries, they have not been broadly
      employed in resource-limited settings (RLS). To investigate the feasibility and
      the types of medical content used by HCW in RLS, we studied one Internet-based
      medical resource used in the United States, (UpToDate(c)) in four hospitals in
      Africa. Health care workers were trained on how to use this resource and surveyed
      over a six month study period. Automated topic tracking found that HCW searched a
      variety of medical topics. About 78% of HCW reported daily or weekly use of the
      Internet-based medical resource and 70% felt the tool was very useful for
      teaching. All users report the tool increased their clinical knowledge. This
      descriptive study suggests that Internet-based medical information resources are
      feasible in RLS and are accessed for a broad variety of medical topics.
      Supplemental content providing guidance when minimal diagnostic and therapeutic
      options exist could increase its relevance in RLS. With increased availability,
      Internet-based medical information could enhance current global health care
      initiatives to improve providers' knowledge, clinical practice and potentially
      patient outcomes.

PMID- 22621408
TI  - Epigenetic variation during the adult lifespan: cross-sectional and longitudinal
      data on monozygotic twin pairs.
AB  - The accumulation of epigenetic changes was proposed to contribute to the age
      related increase in the risk of most common diseases. In this study on 230
      monozygotic twin pairs (MZ pairs), aged 18-89 years, we investigated the
      occurrence of epigenetic changes over the adult lifespan. Using mass
      spectrometry, we investigated variation in global (LINE1) DNA methylation and in
      DNA methylation at INS, KCNQ1OT1, IGF2, GNASAS, ABCA1, LEP, and CRH, candidate
      loci for common diseases. Except for KCNQ1OT1, interindividual variation in locus
      specific DNA methylation was larger in old individuals than in young individuals,
      ranging from 1.2-fold larger at ABCA1 (P = 0.010) to 1.6-fold larger at INS (P =
      3.7 * 10(-07) ). Similarly, there was more within-MZ-pair discordance in old as
      compared with young MZ pairs, except for GNASAS, ranging from an 8% increase in
      discordance each decade at CRH (P = 8.9 * 10(-06) ) to a 16% increase each decade
      at LEP (P = 2.0 * 10(-08) ). Still, old MZ pairs with strikingly similar DNA
      methylation were also observed at these loci. After 10-year follow-up in elderly
      twins, the variation in DNA methylation showed a similar pattern of change as
      observed cross-sectionally. The age-related increase in methylation variation was
      generally attributable to unique environmental factors, except for CRH, for which
      familial factors may play a more important role. In conclusion, sustained
      epigenetic differences arise from early adulthood to old age and contribute to an
      increasing discordance of MZ twins during aging.

PMID- 22621409
TI  - Spaced education activates students in a theoretical radiological science course:
      a pilot study.
AB  - BACKGROUND: The present study aimed at determining if the addition of spaced
      education to traditional face-to-face lectures increased the time students kept
      busy with the learning content of a theoretical radiological science course.
      METHODS: The study comprised two groups of 21 third-year dental students. The
      students were randomly assigned to a "traditional group" and a "spaced education
      group". Both groups followed a traditional face-to-face course. The intervention
      in the spaced education group was performed in way that these students received e
      mails with a delay of 14 days to each face-to-face lecture. These e-mails
      contained multiple choice questions on the learning content of the lectures. The
      students returned their answers to the questions also by e-mail. On return they
      received an additional e-mail that included the correct answers and additional
      explanatory material.All students of both groups documented the time they worked
      on the learning content of the different lectures before a multiple choice exam
      was held after the completion of the course. All students of both groups
      completed the TRIL questionnaire (Trierer Inventar zur Lehrevaluation) for the
      evaluation of courses at university after the completion of the course. The
      results for the time invested in the learning content and the results of the
      questionnaire for the two groups were compared using the Mann-Whitney-U test.
      RESULTS: The spaced education group spent significantly more time (216.2 +/-
      123.9 min) on keeping busy with the learning content compared to the traditional
      group (58.4 +/- 94.8 min, p < .0005). The spaced education group rated the
      didactics of the course significantly better than the traditional group (p =
      .034). The students of the spaced education group also felt that their needs were
      fulfilled significantly better compared to the traditional group as far as
      communication with the teacher was concerned (p = .022). CONCLUSIONS: Adding
      spaced education to a face-to-face theoretical radiological science course
      activates students in a way that they spend significantly more time on keeping
      busy with the learning content.

PMID- 22621410
TI  - Switching off FRET in the hybrid assemblies of diblock copolymer micelles,
      quantum dots, and dyes by plasmonic nanoparticles.
AB  - Recently, it has been noticed that surface plasmon resonance of metal
      nanoparticles can alter the intrinsic properties of nearby fluorophores. Field
      enhancement and radiative decay engineering are major principles for
      understanding a number of experimental observations such as enhanced and quenched
      emission of fluorophores in the vicinity of metal nanoparticles. At the same
      time, there are apparent similarities between surface-plasmon-coupled
      fluorescence and fluorescence resonance energy transfer (FRET), as both are near
      field through-space interactions. From this perspective, we hypothesize that
      donor-acceptor interaction in the FRET can be altered by metal nanoparticles. Our
      approach is based on diblock copolymer micelles, which have been widely applied
      for nanoscale arrangement of functionalities. By applying self-assembling
      techniques of copolymer micelles to organize the spatial location of
      semiconductor quantum dots, fluorescent dyes, and metal nanoparticles, the FRET
      in hybrid assemblies can be switched off by plasmonic effects.

PMID- 22621411
TI  - Pediatric surgery triage: problems and improvements.
AB  - BACKGROUND: The Canadian Paediatric Triage and Acuity Scale (P-CTAS) is used and
      modified at hospitals as a triage tool for pediatric patients before they are
      seen in emergency rooms. Pediatric surgery patients account for very few of the
      many patients in emergency departments, but they should be triaged as emergency
      or urgent because they might be candidates for surgery. Problems with and
      improvements for triaging pediatric surgery patients using the P-CTAS were
      studied. METHODS: This retrospective study evaluated all patients <16 years old
      who visited the emergency department of Kyorin University Hospital during an
      approximately 4 year period between 1 May 2005, and 11 February 2009. Pediatric
      surgery patients were divided into two groups to evaluate the efficiency of P
      CTAS triage. Patients who needed emergency treatment were in group A, and the
      others were in group B. RESULTS: Most group A patients were level I, II, or III
      (97%, 111/114). In contrast, 60% (71/119) of group B patients were level IV or
      greater. Some problems with and suggestions for the P-CTAS were identified. Many
      patients with trauma were under 1 year of age, and many with a foreign body were
      under 2 years of age. Age categories should be added for patients with trauma or
      foreign body aspiration. Patients with abdominal pain, and without anal bleeding
      or vomiting who are >2 years old are triaged as level IV and they accounted for
      12% of patients with possible intussusception in this study. A category of
      'possible intussusception' should be made for level II. Most patients with acute
      scrotum, whether operated on or not, were level III. 'Red or purple color of
      scrotal skin' and/or 'within 6 h from onset' could be added to level II for
      patients with acute scrotum. CONCLUSIONS: P-CTAS worked well for pediatric
      surgery patients, and it needs to be modified and improved for such patients
      based on these results.

PMID- 22621412
TI  - Relative embryo length as an adaptation to habitat and life cycle in Apiaceae.
AB  - * The factors driving the evolution of the relative embryo length in Apiaceae
      were examined. We tested the hypothesis that seeds with large relative embryo
      length, because of more rapid germination, are beneficial in dry and open
      habitats and for short-lived species. We also analyzed to what extent delayed
      germination as a result of embryo growth can be considered a dormancy mechanism.
      * Hypotheses were tested by correlating the relative embryo length with other
      plant traits, habitat and climatic variables. The adaptive nature of the relative
      embryo length was determined by comparing the performance of a pure drift,
      Brownian motion (BM) model of trait evolution with that of a selection-inertia,
      Ornstein-Uhlenbeck (OU) model. * A positive correlation of the relative embryo
      length with germination speed and negative correlations with the amount of
      habitat shade, longevity and precipitation were found. An OU model, in which the
      evolution of longer embryos corresponded to a transition to habitats of high
      light, or to a short life cycle, outperformed significantly a BM model. * The
      results indicated that the relative embryo length may have evolved as an
      adaptation to habitat and life cycle, whereas dormancy was mainly related to
      temperature at the sampling sites.

PMID- 22621413
TI  - Transferring chromosome DNA fragments from multiple donor cells into a host
      strain for yeast strain improvement.
AB  - Based on a common biological phenomenon - homologous recombination - a novel
      method was developed by transferring chromosome DNA fragments extracted from
      multiple donor cells into a host strain. Through this method of transferring DNA
      fragments, foreign DNA fragments are introduced into one host cell and multiple
      positive traits from multiple strains may be integrated into the host strain. We
      first confirmed its feasibility in both prokaryotic and eukaryotic cells by
      selecting reverse mutants to prototrophy from auxotrophic strains through
      receiving chromosomal DNA fragments of wild-type parental strains. We then
      applied this method to Saccharomyces cerevisiae to improve its ethanol and
      temperature tolerance. We introduced donor chromosome DNA fragments from
      different S. cerevisiae strains with improvements in ethanol or temperature
      tolerance into a common strain S. cerevisiae and obtained a strain with much
      superior ethanol and temperature tolerance. The results showed that the
      Transferring DNA Fragments method provides a new way for strain breeding.

PMID- 22621414
TI  - Brachial plexus block in phantom limb pain: not only interesting, but (sometimes)
      with clinical benefit.

PMID- 22621415
TI  - Body weight increment in patients treated with infliximab for plaque psoriasis.
AB  - BACKGROUND: Psoriasis is frequently associated with overweight and obesity. Anti
      TNF-alpha therapies are effective in the treatment of psoriasis. TNF-alpha is
      highly involved in body weight regulation. OBJECTIVE: Our objective was to
      evaluate the increase in weight throughout the treatment with infliximab and the
      association of weight gain with the body mass index (BMI). METHODS: Thirty-five
      patients affected with severe plaque psoriasis receiving infliximab were
      included. A control group consisted of 16 patients affected with severe plaque
      psoriasis and treated with cyclosporine, methotrexate, or acitretin. Assessment
      of PASI score, body weight and BMI were performed at a 1 and 3-year follow-up.
      RESULTS: We observed a body weight increment of 2.5 +/- 4.4 kg (mean +/- SD)
      (i.e. + 3.6% of baseline) and 0.1 +/- 5 kg (i.e. + 1.2%) in patients treated with
      infliximab and the control group, respectively (P = 0.046), after 1 year of
      treatment. After 3 years of infliximab administration, weight gain was 4.8 +/- 5
      kg (n = 16) (i.e. + 6%) (P = 0.005). Moreover, as classified by BMI, normal
      weight patients experienced a 4 +/- 3.7 kg weight gain (i.e. + 6%) whereas
      overweight and obese patients had gained 1.3 +/- 4.8 kg (i.e. + 1.2%) (P = 0.039)
      after 1 year of anti-TNF-alpha therapy. Percentual changes in body weight were
      larger in normal weight patients at baseline than in overweight/obese
      counterparts (P = 0.0149). CONCLUSION: All patients, including normal weight
      patients, should receive a dietary intervention.

PMID- 22621416
TI  - Computed tomography and pathological findings of five nasal neurilemmomas.
AB  - OBJECTIVES: Neurilemmomas are benign tumors deriving from Schwann cells of the
      nerve sheath. They occur in all parts of the body. The highest incidence of
      neurilemmoma is in the head and neck region (38-45%), but involvement of the nose
      and paranasal sinus is quite rare, with only sporadic cases having been reported
      in the world literature. Fewer than 4% of these tumors involve the nasal cavity
      and paranasal sinuses. We describe the clinical, pathologic, and computed
      tomography (CT) features of five nasal neurilemmomas. METHODOLOGY: CT features of
      five patients with nasal schwannoma proved by operation and pathology were
      investigated. RESULTS: Schwannomas tend to be solitary and are usually well
      circumscribed tumors with an oval, round or fusiform shape in the unilateral
      nasal cavity. The lesions usually have a mottled central lucency with peripheral
      intensification on contrast-enhanced CT scans. The heterogeneous appearance is
      related to areas of increased vascularity with adjacent non-enhancing cystic or
      necrotic regions. CONCLUSIONS: Schwannoma should be considered in the
      differential of unusual nasal masses. Certain clinical and CT patterns may be of
      use in the differential diagnosis.

PMID- 22621417
TI  - Effects of non-neurological complications on traumatic brain injury outcome.
AB  - Traumatic brain injury (TBI) affects over 1.5 million Americans annually and
      consumes a significant amount of healthcare dollars. Identification of
      complications and factors that impact recovery from TBI is important in improving
      outcome and allocating appropriate resources. Understanding the role of non
      neurologic complications such as sepsis, acute kidney injury, and respiratory
      problems on TBI outcome and mortality is critical. 

PMID- 22621418
TI  - Mechanistic analysis of gold(I)-catalyzed intramolecular allene hydroalkoxylation
      reveals an off-cycle bis(gold) vinyl species and reversible C-O bond formation.
AB  - Mechanistic investigation of gold(I)-catalyzed intramolecular allene
      hydroalkoxylation established a mechanism involving rapid and reversible C-O bond
      formation followed by turnover-limiting protodeauration from a mono(gold) vinyl
      complex. This on-cycle pathway competes with catalyst aggregation and formation
      of an off-cycle bis(gold) vinyl complex.

PMID- 22621420
TI  - Primary care update--light at the end of the tunnel?

PMID- 22621421
TI  - Biomarkers unbound--the Supreme Court's ruling on diagnostic-test patents.

PMID- 22621419
TI  - The six most essential questions in psychiatric diagnosis: a pluralogue part 3:
      issues of utility and alternative approaches in psychiatric diagnosis.
AB  - In face of the multiple controversies surrounding the DSM process in general and
      the development of DSM-5 in particular, we have organized a discussion around
      what we consider six essential questions in further work on the DSM. The six
      questions involve: 1) the nature of a mental disorder; 2) the definition of
      mental disorder; 3) the issue of whether, in the current state of psychiatric
      science, DSM-5 should assume a cautious, conservative posture or an assertive,
      transformative posture; 4) the role of pragmatic considerations in the
      construction of DSM-5; 5) the issue of utility of the DSM - whether DSM-III and
      IV have been designed more for clinicians or researchers, and how this conflict
      should be dealt with in the new manual; and 6) the possibility and advisability,
      given all the problems with DSM-III and IV, of designing a different diagnostic
      system. Part 1 of this article took up the first two questions. Part 2 took up
      the second two questions. Part 3 now deals with Questions 5 & 6. Question 5
      confronts the issue of utility, whether the manual design of DSM-III and IV
      favors clinicians or researchers, and what that means for DSM-5. Our final
      question, Question 6, takes up a concluding issue, whether the acknowledged
      problems with the earlier DSMs warrants a significant overhaul of DSM-5 and
      future manuals. As in Parts 1 & 2 of this article, the general introduction, as
      well as the introductions and conclusions for the specific questions, are written
      by James Phillips, and the responses to commentaries are written by Allen
      Frances.

PMID- 22621422
TI  - 125I-radiolabeled morpholine-containing arginine-glycine-aspartate (RGD) ligand
      of alphavbeta3 integrin as a molecular imaging probe for angiogenesis.
AB  - In this paper, using a hybrid small-animal Micro SPECT/CT imaging system, we
      report that a new (125)I-Cilengitide-like RGD-cyclopentapeptide, containing d
      morpholine-3-carboxylic acid, interacts in vivo with alpha(v)beta(3) integrin
      expressed by melanoma cells. Images clearly show that the (125)I-compound has the
      capacity to monitor the growth of a melanoma xenograft. Indeed, retention of the
      labeled ligand in the tumor mass has a good tumor/background ratio, and a
      significant reduction of its uptake was observed after injection of unlabeled
      ligand. These results suggest that the use of (125)I-labeled morpholine-based RGD
      cyclopentapeptides targeting alpha(v)beta(3) positive tumors may play a role in
      future therapeutic strategies.

PMID- 22621425
TI  - Alcohol intake and its effect on some appetite-regulating hormones in man:
      influence of gastroprotection with sucralfate.
AB  - BACKGROUND: Alcohol stimulates appetite. Ghrelin, obestatin, glucagon-like
      peptide 1 and leptin are putative mediators. OBJECTIVE: We studied whether
      alcohol ingestion affects serum levels of these peripheral hormones, and if
      gastroprotective sucralfate prevents such an effect. MATERIALS AND METHODS: Ten
      participants were investigated on four occasions. On one alcohol was ingested; on
      another alcohol was given after pretreatment with sucralfate; on a third water
      was ingested; and on a fourth sucralfate was ingested followed by water. Serum
      hormones and ethanol concentrations were determined. RESULTS: The ghrelin and
      leptin levels fell after ingestion of alcohol, whereas the obestatin and GLP-1
      levels remained unchanged. Sucralfate did not affect any of the basal four
      hormone levels, nor the ghrelin or leptin responses to alcohol. CONCLUSIONS: An
      appetite-stimulating effect of alcohol is hardly mediated by any of the hormones
      studied in this investigation, as the GLP-1 and obestatin levels were unaffected
      by alcohol, the ghelin level decreased, and leptin - although declining after
      alcohol - has not previously been found to have short-term inhibitory effect on
      hunger.

PMID- 22621426
TI  - Optical spectroscopy study of organic-phase lanthanide complexes in the TALSPEAK
      separations process.
AB  - Time-resolved fluorescence spectroscopy and Fourier transform IR spectroscopy
      have been applied to characterize the coordination environment of lipophilic
      complexes of Eu(3+) with bis(2-ethylhexyl)phosphoric acid (HDEHP) and (2
      ethylhexyl)phosphonic acid mono(2-ethylhexyl) ester (HEH[EHP]) in 1,4
      diisopropylbenzene (DIPB). The primary focus is on understanding the role of
      lactate (HL) in lanthanide partitioning into DIPB solutions of HDEHP or HEH[EHP]
      as it is employed in the TALSPEAK solvent extraction process for lanthanide
      separations from trivalent actinides. The broader purpose of this study is to
      characterize the changes that can occur in the coordination environment of
      lanthanide ions as metal-ion concentrations increase in nonpolar media. The
      optical spectroscopy studies reported here complement an earlier investigation of
      similar solutions using NMR spectroscopy and electrospray ionization mass
      spectrometry. Emission spectra of Eu(3+) complexes with HDEHP/HEH[EHP]
      demonstrate that, as long as the Eu(3+) concentration is maintained well below
      saturation of the organic extractant solution, the Eu(3+) coordination
      environment remains constant as both [HL](org) and [H(2)O](org) are increased. If
      the total organic-phase lanthanide concentration is increased (by extraction of
      moderate amounts of La(3+)), the (5)D(0) -> (7)F(1) transition singlet splits
      into a doublet with a notable increase in the intensity of both (5)D(0) ->
      (7)F(1) and (5)D(0) -> (7)F(2) electronic transitions. The increased multiplicity
      in the emission spectra indicates that Eu(3+) ions are present in multiple
      coordination environments. The increased emission intensity of the 614 nm band
      implies an overall reduction in symmetry of the extracted Eu(3+) complex in the
      presence of macroscopic La(3+). Although [H(2)O](org) increases to above 1 M at
      high [HL](tot), this water is not associated with the Eu(3+) metal center. IR
      spectroscopy results confirm a direct Ln(3+)-lactate interaction at high
      concentrations of lanthanide and lactate in the extractant phase. At low organic
      phase lanthanide concentrations, the predominant complex is almost certainly the
      well-known Ln(DEHP.HDEHP)(3). As lanthanide concentrations in the organic phase
      increase, mixed-ligand complexes with the general stoichiometry Ln(L)(n)(DEHP)(3
      n) or Ln(L)(n)(DEHP.HDEHP)(3-n) become the dominant species.

PMID- 22621423
TI  - Immunocytochemical analysis of P2X2 in rat circumvallate taste buds.
AB  - BACKGROUND: Our laboratory has shown that classical synapses and synaptic
      proteins are associated with Type III cells. Yet it is generally accepted that
      Type II cells transduce bitter, sweet and umami stimuli. No classical synapses,
      however, have been found associated with Type II cells. Recent studies indicate
      that the ionotropic purinergic receptors P2X2/P2X3 are present in rodent taste
      buds. Taste nerve processes express the ionotropic purinergic receptors
      (P2X2/P2X3). P2X2/P2X3(Dbl-/-) mice are not responsive to sweet, umami and bitter
      stimuli, and it has been proposed that ATP acts as a neurotransmitter in taste
      buds. The goal of the present study is to learn more about the nature of
      purinergic contacts in rat circumvallate taste buds by examining immunoreactivity
      to antisera directed against the purinergic receptor P2X2. RESULTS: P2X2-like
      immunoreactivity is present in intragemmal nerve processes in rat circumvallate
      taste buds. Intense immunoreactivity can also be seen in the subgemmal nerve
      plexuses located below the basal lamina. The P2X2 immunoreactive nerve processes
      also display syntaxin-1-LIR. The immunoreactive nerves are in close contact with
      the IP(3)R3-LIR Type II cells and syntaxin-1-LIR and/or 5-HT-LIR Type III cells.
      Taste cell synapses are observed only from Type III taste cells onto P2X2-LIR
      nerve processes. Unusually large, "atypical" mitochondria in the Type II taste
      cells are found only at close appositions with P2X2-LIR nerve processes. P2X2
      immunogold particles are concentrated at the membranes of nerve processes at
      close appositions with taste cells. CONCLUSIONS: Based on our immunofluorescence
      and immunoelectron microscopical studies we believe that both perigemmal and most
      all intragemmal nerve processes display P2X2-LIR. Moreover, colloidal gold
      immunoelectron microscopy indicates that P2X2-LIR in nerve processes is
      concentrated at sites of close apposition with Type II cells. This supports the
      hypothesis that ATP may be a key neurotransmitter in taste transduction and that
      Type II cells release ATP, activating P2X2 receptors in nerve processes.

PMID- 22621427
TI  - Positive fluid balance is associated with reduced survival in critically ill
      patients with cancer.
AB  - BACKGROUND: There are no studies that describe the impact of the cumulative fluid
      balance on the outcomes of cancer patients admitted to intensive care units ICUs.
      The aim of our study was to evaluate the relationship between fluid balance and
      clinical outcomes in these patients. METHOD: One hundred twenty-two cancer
      patients were prospectively evaluated for survival during a 30-day period.
      Univariate (Chi-square, t-test, Mann-Whitney) and multiple logistic regression
      analyses were used to identify the admission parameters associated with
      mortality. RESULTS: The mean cumulative fluid balance was significantly higher in
      non-survivors than in survivors [1675 ml/24 h (471-2921) vs. 887 ml/24 h (104
      557), P = 0.017]. We used the area under the curve and the intersection of the
      sensibility and specificity curves to define a cumulative fluid balance value of
      1100 ml/24 h. This value was used in the univariate model. In the multivariate
      model, the following variables were significantly associated with mortality in
      cancer patients: the Acute Physiology and Chronic Health Evaluation II score at
      admission [Odds ratio (OR) 1.15; 95% confidence interval (CI) (1.05-1.26), P =
      0.003], the Lung Injury Score at admission [OR 2.23; 95% CI (1.29-3.87), P =
      0.004] and a positive fluid balance higher than 1100 ml/24 h at ICU [OR 5.14; 95%
      CI (1.45-18.24), P = 0.011]. CONCLUSION: A cumulative positive fluid balance
      higher than 1100 ml/24 h was independently associated with mortality in patients
      with cancer. These findings highlight the importance of improving the evaluation
      of these patients' volemic state and indicate that defined goals should be used
      to guide fluid therapy.

PMID- 22621428
TI  - Recurrent pregnancy loss - beyond evidence based medicine.
AB  - Patients with five or more unexplained recurrent pregnancy losses (RPL) have a
      poor prognosis for a subsequent delivery compared to patients with two to three
      RPL. Treatment guidelines are needed to address this select group of patients.

PMID- 22621430
TI  - Molecular interaction of proteins and peptides with nanoparticles.
AB  - The interaction of proteins in living cells is one of the key processes in the
      maintenance of their homeostasis. Introduction of additional agents into the
      chain of these interactions may influence homeostatic processes. Recent advances
      in nanotechnologies have led to a wide use of nanoparticles (NPs) in industrial
      and biomedical applications. NPs are small enough to enter almost all
      compartments of the body, including cells and organelles, and to complicate the
      pattern of protein interactions. In some cases, interaction of nanoscale objects
      with proteins leads to hazardous consequences, such as abnormal conformational
      changes leading to exposure of cryptic peptide epitopes or the appearance of
      abnormal functions caused by structural modifications. In addition, the high
      local protein concentration resulting from protein adsorption on NPs may provoke
      avidity effects arising from close spatial repetition of the same protein.
      Finally, the interaction of NPs with proteins is known to induce cooperative
      effects, such as promotion or inhibition of protein fibrillation or self
      assembling of NPs on macromolecules serving as a template. It is obvious that
      better understanding of the molecular mechanisms of nano-bio interactions is
      crucial for further advances in all nanotechnological applications. This review
      summarizes recent progress in understanding the molecular mechanisms of the
      interactions between proteins or peptides and NPs in order to predict the
      structural, functional, and/or nanotoxic consequences of these interactions.

PMID- 22621431
TI  - A virtual plant that responds to the environment like a real one: the case for
      chrysanthemum.
AB  - * Plants respond to environmental change through alterations in organ size,
      number and biomass. However, different phenotypes are rarely integrated in a
      single model, and the prediction of plant responses to environmental conditions
      is challenging. The aim of this study was to simulate and predict plant
      phenotypic plasticity in development and growth using an organ-level functional
      structural plant model, GreenLab. * Chrysanthemum plants were grown in climate
      chambers in 16 different environmental regimes: four different temperatures (15,
      18, 21 and 24 degrees C) combined with four different light intensities (40%,
      51%, 65% and 100%, where 100% is 340 MUmol m-2 s-1). Measurements included plant
      height, flower number and major organ dry mass (main and side-shoot stems, main
      and side-shoot leaves and flowers). To describe the basipetal flowering sequence,
      a position-dependent growth delay function was introduced into the model. * The
      model was calibrated on eight treatments. It was capable of simulating multiple
      plant phenotypes (flower number, organ biomass, plant height) with visual output.
      Furthermore, it predicted well the phenotypes of the other eight treatments
      (validation) through parameter interpolation. * This model could potentially
      serve to bridge models of different scales, and to link energy input to crop
      output in glasshouses.

PMID- 22621432
TI  - Influence of collector surface composition and water chemistry on the deposition
      of cerium dioxide nanoparticles: QCM-D and column experiment approaches.
AB  - The deposition behavior of cerium dioxide (CeO(2)) nanoparticles (NPs) in dilute
      NaCl solutions was investigated as a function of collector surface composition,
      pH, ionic strength, and organic matter (OM). Sensors coated separately with
      silica, iron oxide, and alumina were applied in quartz crystal microbalance with
      dissipation (QCM-D) to examine the effect of these mineral phases on CeO(2)
      deposition in NaCl solution (1-200 mM). Frequency and dissipation shift followed
      the order: silica > iron oxide > alumina in 10 mM NaCl at pH 4.0. No significant
      deposition was observed at pH 6.0 and 8.5 on any of the tested sensors. However,
      >= 94.3% of CeO(2) NPs deposited onto Ottawa sand in columns in 10 mM NaCl at pH
      6.0 and 8.5. The inconsistency in the different experimental approaches can be
      mainly attributed to NP aggregation, surface heterogeneity of Ottawa sand, and
      flow geometry. In QCM-D experiments, the deposition kinetics was found to be
      qualitatively consistent with the predictions based on the classical colloidal
      stability theory. The presence of low levels (1-6 mg/L) of Suwannee River humic
      acid, fulvic acid, alginate, citric acid, and carboxymethyl cellulose greatly
      enhanced the stability and mobility of CeO(2) NPs in 1 mM NaCl at pH 6.5. The
      poor correlation between the transport behavior and electrophoretic mobility of
      CeO(2) NPs implies that the electrosteric effect of OM was involved.

PMID- 22621433
TI  - Umbilical cord mesenchymal stem cell transplantation in drug-induced Stevens
      Johnson syndrome.

PMID- 22621434
TI  - ROTEM(r)-guided coagulation factor concentrate therapy in trauma: 2-year
      experience in Venice, Italy.

PMID- 22621435
TI  - Controlled synthesis and magnetic properties of bimagnetic spinel ferrite CoFe2O4
      and MnFe2O4 nanocrystals with core-shell architecture.
AB  - A combination of hard phase CoFe(2)O(4) and soft phase MnFe(2)O(4) as the
      bimagnetic nanocrystals in a core-shell architecture has been synthesized, and
      their magnetic properties have been systematically studied. Both HRTEM and EDS
      results confirmed the formation of bimagnetic core-shell structured nanocrystals.
      On the basis of the systematic and comparative studies of the magnetic properties
      of a mechanical mixture of pure CoFe(2)O(4) and MnFe(2)O(4) nanocrystals,
      chemically mixed Co(1-x)Mn(x)Fe(2)O(4) nanocrystals, and bimagnetic core-shell
      CoFe(2)O(4)@MnFe(2)O(4) and MnFe(2)O(4)@CoFe(2)O(4) nanocrystals, the bimagnetic
      core-shell nanocrystals show very unique magnetic properties, such as the
      blocking temperature and coercivity. Our results show that the coercivity
      correlates with the volume fraction of the soft phase as the theoretical hard
      soft phase model has suggested. Furthermore, switching the hard phase CoFe(2)O(4)
      from the core to the shell shows great changes in the coercivity of the
      nanocrystals. The bimagnetic core-shell nanocrystals evidently demonstrate the
      rational design capability to separately control the blocking temperature and the
      coercivity in magnetic nanocrystals by varying the materials, their combination,
      and the volume ratio between the core and the shell and by switching hard or soft
      phase materials between the core and shell. Such controls via a bimagnetic core
      shell architecture are highly desirable for magnetic nanocrystals in various
      applications.

PMID- 22621436
TI  - The results of percutaneous intradiscal high-pressure injection of saline in
      patients with extruded lumbar herniated disc: comparison with microendoscopic
      discectomy.
AB  - OBJECTIVES: Intradiscal high-pressure injection of saline (IDHP) is a noninvasive
      procedure for a lumbar intervertebral disc extrusion and an alternative treatment
      to surgery, such as microendoscopic discectomy (MED). The purpose of this study
      was to compare the representative outcomes of IDHP with MED in terms of pain
      relief, reduction of disability, and risk of complications. METHODS: Forty-five
      patients with primarily radicular pain due to an extrusion type disc herniation
      who underwent either IDHP (N = 24) or MED (N = 21) were enrolled in the study.
      The visual analog pain scale (VAS) and the Japanese Orthopedic Association (JOA)
      scoring system for the treatment of low-back disorders were assessed at
      pretreatment, 2 weeks posttreatment, and JOA was again taken 3 months
      posttreatment. Patients were asked to choose their satisfaction from four
      alternatives, "excellent,""good,""fair," and "poor," 3 months after treatment.
      RESULTS: Mean VAS decreased from 65.1 to 18.8 mm in the IDHP group, and from 80.6
      to 16.5 in the MED group. Mean JOA recovery rates at 3 months posttreatment were
      67.2 and 75.2, and patients with "excellent" or "good" results were 73.7% and
      78.6% in the IDHP and in MED, respectively. CONCLUSIONS: IDHP produced
      significant effects on patients with radicular pain, leading to the improvement
      of VAS and JOA. Although IDHP displayed slightly less efficacy than MED, IDHP
      appears to be an alternative as a nonoperative treatment for a lumbar
      intervertebral disc extrusion.

PMID- 22621438
TI  - Quality of life in children and adolescents with respiratory allergy, assessed
      with a generic and disease-specific instrument.
AB  - INTRODUCTION: Respiratory allergic disorders like rhinitis and asthma are common
      conditions that not only affect target organs, but complicate the daily life of
      affected children and adolescents. OBJECTIVES: The aim of this study was to
      investigate the QoL (quality of life) in children with grass pollen allergy in
      and out of grass pollen season. METHODS: We used the Pediatric Allergic Disease
      Quality of Life Questionnaire (PADQLQ), a disease-specific questionnaire
      including both asthma and rhinitis symptoms. We also used the DISABKIDS (a
      European project which aims at enhancing the quality of life and the independence
      of children with chronic health conditions and their families) questionnaire, a
      generic questionnaire covering non-organ-specific effects of disease. RESULTS:
      Ninety-eight children 7-18 years old with grass pollen allergy were included.
      Eighty-nine children (91%) completed the study. The QoL was significantly
      decreased during pollen season assessed both with DISABKIDS and PADQLQ. The
      correlation between the questionnaires was 0.73. Not only the physical domain
      score (P = 0.00093) but also the emotional domain score (P = 0.034) was
      significantly lowered. Children with multiple manifestations (asthma and
      rhinitis) had lower QoL than children with rhinitis alone (P = 0.01). Multiple
      regression analysis showed a highly significant impact on QoL for symptoms from
      nose, eyes and lungs. They were equally important (standardized coefficient 047,
      0.47 and 0.46, respectively). CONCLUSION: The QoL in children and adolescents
      with respiratory allergy deteriorates during pollen season. This was shown both
      with generic (DISABKIDS) and disease-specific instrument (PADQLQ).

PMID- 22621437
TI  - Impairment of osteoblast differentiation due to proliferation-independent
      telomere dysfunction in mouse models of accelerated aging.
AB  - We undertook genetic and nongenetic approaches to investigate the relationship
      between telomere maintenance and osteoblast differentiation, as well as to
      uncover a possible link between a known mediator of cellular aging and senile
      bone loss. Using mouse models of disrupted telomere maintenance molecules,
      including mutants in the Werner helicase (Wrn(-/-) ), telomerase (Terc(-/-) ),
      and Wrn(-/-)  Terc(-/-)  double mutants predisposed to accelerated bone loss, we
      measured telomere dysfunction-induced foci (TIFs) and markers of osteoblast
      differentiation in mesenchymal progenitor cells (MPCs). We found that telomere
      maintenance is directly and significantly related to osteoblast differentiation,
      with dysfunctional telomeres associated with impaired differentiation independent
      of proliferation state. Telomere-mediated defects in osteoblast differentiation
      are associated with increased p53/p21 expression and concomitant reduction in
      RUNX2. Conversely, MPCs from p53(-/-)  mice do not have substantial telomere
      dysfunction and spontaneously differentiate into osteoblasts. These results
      suggest that critical telomere dysfunction may be a prominent mechanism for age
      related osteoporosis and limits MPC differentiation into bone-forming cells via
      the p53/p21 pathway.

PMID- 22621439
TI  - Factors associated with intern noncompliance with the 2003 Accreditation Council
      for Graduate Medical Education's 30-hour duty period requirement.
AB  - BACKGROUND: In 2003 the Accreditation Council for Graduate Medical Education
      mandated work hour restrictions. Violations can results in a residency program
      being cited or placed on probation. Recurrent violations could results in loss of
      accreditation. We wanted to determine specific intern and workload factors
      associated with violation of a specific mandate, the 30-hour duty period
      requirement. METHODS: Retrospective review of interns' performance against the 30
      hour duty period requirement during inpatient ward rotations at a pediatric
      residency program between June 24, 2008 and June 23, 2009. The analytical plan
      included both univariate and multivariable logistic regression analyses. RESULTS:
      Twenty of the 26 (77%) interns had 80 self-reported episodes of continuous work
      hours greater than 30 hours. In multivariable analysis, noncompliance was
      inversely associated with the number of prior inpatient rotations (odds ratio:
      0.49, 95% confidence interval (0.38, 0.64) per rotation) but directly associated
      with the total number of patients (odds ratio: 1.30 (1.10, 1.53) per additional
      patient). The number of admissions on-call, number of admissions after midnight
      and number of discharges post-call were not significantly associated with
      noncompliance. The level of noncompliance also varied significantly between
      interns after accounting for intern experience and workload factors. Subject to
      limitations in statistical power, we were unable to identify specific intern
      characteristics, such as demographic variables or examination scores, which
      account for the variation in noncompliance between interns. CONCLUSIONS: Both
      intern and workload factors were associated with pediatric intern noncompliance
      with the 30-hour duty period requirement during inpatient ward rotations.
      Residency programs must develop information systems to understand the individual
      and experience factors associated with noncompliance and implement appropriate
      interventions to ensure compliance with the duty hour regulations.

PMID- 22621441
TI  - R2 and R2/R1 hybrid non-autonomous retrotransposons derived by internal deletions
      of full-length elements.
AB  - BACKGROUND: R2 is a non-long terminal repeat (non-LTR) retrotransposable element
      that inserts site specifically into the 28S genes of the ribosomal (r)RNA gene
      loci. Encoded at the 5' end is a ribozyme that generates the precise 5' end by
      self-cleavage of a 28S gene cotranscript. Sequences at the 3' end are necessary
      for the R2 protein to bind RNA and initiate the target primed reverse
      transcription (TPRT) reaction. These minimal RNA requirements suggested that if
      recombination/DNA repair conjoined the 5' and 3' ends of R2, the result would be
      a non-autonomous element that could survive as long as autonomous R2 elements
      supplied the TPRT activity. RESULTS: A PCR-based survey of 39 Drosophila species
      aided by genomic sequences from 12 of these species revealed two types of non
      autonomous elements. We call these elements SIDEs (for 'Short Internally Deleted
      Elements'). The first consisted of a 5' ribozyme and a 3' end of an R2 element as
      predicted. Variation at the 5' junctions of the R2 SIDE copies was typical for R2
      insertions suggesting their propagation by TPRT. The second class of SIDE
      contained sequences from R1 elements, another non-LTR retrotransposon that
      inserts into rRNA gene loci. These insertions had an R2 ribozyme immediately
      upstream of R1 3' end sequences. These hybrid SIDEs were inserted at the R1 site
      with 14 bp target site duplications typical of R1 insertions suggesting they used
      the R1 machinery for retrotransposition. Finally, the survey revealed examples of
      U12 small nuclear (sn)RNA and tRNA sequences at the 5' end of R2 elements
      suggesting the R2 reverse transcriptase can template jump from the R2 transcript
      to a second RNA during TPRT. CONCLUSIONS: The R2 SIDE and R2/R1 hybrid SIDEs are
      rare examples of non-autonomous retrotransposons in the Drosophila genome.
      Associated non-autonomous elements and in vivo template jumps are two additional
      characteristics R2 shares with other non-LTR retrotransposons such as mammalian
      L1s. Analysis of the hybrid SIDEs provides supporting evidence that R1 elements,
      like R2 elements, recognize their 3' untranslated region (UTR) sequences and,
      thus, belong to the stringent class of non-LTR elements.

PMID- 22621442
TI  - Post-conditioning by xenon reduces ischaemia-reperfusion injury of the spinal
      cord in rats.
AB  - BACKGROUND: The neuroprotective effects of xenon post-conditioning following
      spinal cord injury remain unknown. We monitored the effect of xenon post
      conditioning on the spinal cord following ischaemia-reperfusion injury and
      determined its mechanism of action. METHODS: Spinal cord ischaemia was induced
      following balloon occlusion of the thoracic aorta in male Sprague-Dawley rats.
      Rats were divided into three groups (n = 30 in each group). The control group
      underwent ischaemia-reperfusion injury and immediately inhaled 50% (v/v) nitrogen
      at the time of reperfusion for 60 min continuously. The xenon-post-conditioning
      group underwent the same surgical procedure and immediately inhaled 50% (v/v)
      xenon at the time of reperfusion for 60 min continuously. The sham operation
      group underwent the same surgical procedure without aortic catheter occlusion and
      inhaled the same gas as that in control rats. Neurologic function was assessed
      using the Basso, Beattie, and Bresnahan score at 4, 24, and 48 h after
      reperfusion. Histological changes were observed using Nissl staining, the
      ultrastructure of the spinal cord was examined using transmission electron
      microscopy, and apoptosis was monitored using terminal deoxynucleotidyl
      transferase-mediated deoxyuridine triphosphate nick-end labelling. RESULTS:
      Compared with the control group, the xenon-post-conditioning group showed
      improved neurologic outcomes (11.3 +/- 1.6 vs. 15.7 +/- 3.1, respectively) and
      had more morphologically normal neurons (6 +/- 2 vs. 12 +/- 3) at 48 h after
      reperfusion. Moreover, apoptotic cell death in xenon-treated rats was reduced
      when compared with control rats (18.29 +/- 3.06 vs. 27.34 +/- 3.63, P < 0.05,
      respectively). CONCLUSIONS: Xenon post-conditioning exerts a neuroprotective
      effect on the spinal cord following ischaemia-reperfusion injury via its anti
      apoptotic role.

PMID- 22621443
TI  - A new preventive strategy for hypoglycemia incorporating added food diet in
      patients with type 2 diabetes who received sitagliptin therapy.
AB  - There has been concern as to whether dipeptidyl peptidase-4 (DPP-4) inhibitors
      can be used safely in patients with relatively good glycemic control. This study,
      approved by the institutional review board of Hanzoumon Diabetes City Atlas
      Clinic, examined whether DPP-4 inhibitor sitagliptin could safely achieve good
      glycemic control without severe hypoglycemia by employing the "added food"
      concept. The subjects were 60 patients (46 men and 14 women) with type 2 diabetes
      who started sitagliptin therapy during a 1-month period from December 15, 2009 to
      January 15, 2010. They were recommended to have added food between meals to
      prevent hypoglycemia, while maintaining the same daily calorie intake. HbA(1c)
      decreased from 7.1 +/- 1.2% to 6.5 +/- 0.6% after 6 months of sitagliptin
      treatment (p < 0.001). In patients with a baseline HbA(1c) <7%, it decreased from
      6.5 +/- 0.3% to 6.1 +/- 0.4% (p < 0.001). Systolic blood pressure was
      significantly reduced from 127.7 +/- 17.0 to 122.7 +/- 17.9 mmHg in the patients
      with a baseline HbA(1c) < 7% (p = 0.018). However, body weight increased by
      approximately 900 g and high-density lipoprotein cholesterol decreased
      significantly from 1.57 +/- 0.46 to 1.43 +/- 0.35 mmol/L (p < 0.01) in the
      patients concomitantly receiving sulfonylureas with sitagliptin. Excellent
      glycemic control was achieved by sitagliptin treatment together with the added
      food concept. However, combined use of sitagliptin with sulfonylureas requires
      attention to weight gain and the lipid profile. Further clinical studies will
      elucidate whether sitagliptin can decrease cardiovascular events as well as
      normalizing blood glucose and lowering the blood pressure.

PMID- 22621452
TI  - X-ray absorption spectroscopy of an investigational anticancer gallium(III) drug:
      interaction with serum proteins, elemental distribution pattern, and coordination
      of the compound in tissue.
AB  - Tris(8-quinolinolato)gallium(III) (1, KP46) is a very promising investigational
      anticancer drug. Its interaction with serum proteins, elemental distribution, and
      coordination in tissue were investigated with X-ray absorption (XAS) methods.
      Model compounds with mixed O, N, and/or S donor atoms are reported. The
      coordination and structure of 1 in cell culture medium (minimum essential medium,
      MEM) and fetal calf serum (FCS) were probed by XANES and EXAFS. The interaction
      of 1 with the serum proteins apotransferrin (apoTf) and human serum albumin (HSA)
      was addressed as well. By application of micro-XAS to tissue samples from mice
      treated with 1, the gallium distribution pattern was analyzed and compared to
      those of physiological trace elements. The complex 1 turned out to be very stable
      under physiological conditions, in cell culture media and in tissue samples. The
      coordination environment of the metal center remains intact in the presence of
      apoTf and HSA. The gallium distribution pattern in tumor and liver tissue
      revealed high similarities to the distribution patterns of Zn and Fe, minor
      similarities to Cu and Ni, and no similarity to Ca.

PMID- 22621453
TI  - Cross-stage and combination treatment for Barcelona Clinic of Liver Cancer stage
      B (intermediate stage) hepatocellular carcinoma.

PMID- 22621454
TI  - Lessons from Lumiracoxib: are cyclooxygenase-2 inhibitors less hepatotoxic than
      non-selective non-steroidal anti-inflammatory drugs?

PMID- 22621455
TI  - Endoscopic resection of colorectal cancer for cure: are we there yet?

PMID- 22621456
TI  - Education and imaging. Gastrointestinal: MALT lymphoma of the small bowel
      accompanied by NSAID-induced enteropathy.

PMID- 22621457
TI  - Education and imaging. Gastrointestinal: Incidental findings of Ascaris
      Lumbricoides in patient presenting with ureteric colic.

PMID- 22621458
TI  - Education and imaging. Gastrointestinal: Role of endoscopic ultrasound in the
      evaluation of pseudoachalasia.

PMID- 22621459
TI  - Education and imaging. Hepatobiliary and pancreatic: Liver abscess associated
      with lipoma of duodenum.

PMID- 22621460
TI  - Education and imaging. Hepatobiliary and pancreatic: Emphysematous gastritis with
      hepatic portal venous gas.

PMID- 22621463
TI  - Pharmacological reactivity of resistance vessels in a rat PCOS model - vascular
      effects of parallel vitamin D3 treatment.
AB  - The aim of this study was to clarify the effects of dihydrotestosterone (DHT)
      induced polycystic ovary syndrome (PCOS) on pharmacological reactivity of a
      resistance vessel in a rat model and the possible modulatory role of 1,25-(OH)2
      cholecalciferol (vitamin D3). The PCOS model was induced in adolescent female
      Wistar rats by a 10-week DHT treatment. Norepinephrine induced contractility and
      acetylcholine relaxation were tested in arterioles by pressure arteriography in
      control as well as DHT- and DHT plus vitamin D3-treated (DHT+D3) animals.
      Decreased vasoconstriction and dilatation were detected after DHT treatment.
      Concomitant vitamin D3 treatment increased the contractile response and resulted
      in more relaxed vessels. Endothelial dilation tested with acetylcholine was lower
      after DHT treatment, this effect was not depend on vitamin D3 supplementation. In
      conclusion, hyperandrogenic state resulted in reduced endothelium- and smooth
      muscle-dependent vasorelaxation and constriction with a complete loss of nitric
      oxide (NO)-dependent relaxation compared with controls. These alterations caused
      by chronic DHT treatment were partially reversed by concomitant vitamin D3
      administration.

PMID- 22621464
TI  - Sleep problems and mental health in primary school new entrants: cross-sectional
      community-based study.
AB  - AIMS: To determine at school entry (i) the prevalence and types of child sleep
      problems; (ii) sleep difficulties and hygiene practices associated with sleep
      problems; and (iii) their associations with child health-related quality of life,
      mental health and parent mental health. METHODS: We conducted a cross-sectional
      community-based study at 22 primary schools in Melbourne, Australia. One thousand
      five hundred and twelve (70%) parents of children in the first 6 months of the
      child's first year of primary school took part. Parent report of child sleep
      problems (none, mild, and moderate/severe); sleep difficulties; pre-bedtime
      activities (television in bedroom, television or electronic games before bedtime,
      television or electronic games >2 h/day) and caffeine intake; child mental health
      (Strengths and Difficulties Questionnaire), health-related quality of life
      (Pediatric Quality of Life Inventory); and parent mental health (Depression
      Anxiety Stress Scale-21). RESULTS: 38.6% of children had a parent-reported sleep
      problem (27.9% mild, 10.8% moderate/severe). Sleep problems were characterised by
      problematic sleep difficulties but not poor sleep hygiene practices.
      Moderate/severe sleep problems were associated with poorer child mental health
      (mean difference -0.8; 95% confidence interval (CI) -1.1 to -0.5, P < 0.001),
      health-related quality of life (mean difference -9.9; 95% CI -11.9 to -7.9, P <
      0.001) and parent mental health (mean difference 9.8; 95% CI 7.7-11.9, P <
      0.001). CONCLUSIONS: In new school entrants, sleep problems are common and
      associated with poorer child mental health, health-related quality of life and
      parent mental health. Future research needs to determine if systematically
      addressing sleep problems improves these outcomes.

PMID- 22621466
TI  - Sexual violence among host and refugee population in Djohong District, Eastern
      Cameroon.
AB  - The following is a population-based survey of the Central African Republic (CAR)
      female refugee population displaced to rural Djohong District of Eastern Cameroon
      and associated female Cameroonian host population to characterise the prevalence
      and circumstances of sexual violence. A population-based, multistage, random
      cluster survey of 600 female heads of household was conducted during March 2010.
      Women heads of household were asked about demographics, household economy and
      assets, level of education and sexual violence experienced by the respondent
      only. The respondents were asked to describe the circumstances of their recent
      assault. The lifetime prevalence of sexual violence among Djohong district female
      heads of household is 35.2% (95% CI 28.7-42.2). Among heads of household who
      reported a lifetime incident of sexual violence, 64.0% (95% CI 54.3-72.5)
      suffered sexual violence perpetrated by their husband or partner. Among the host
      population, 3.9% (95% CI 1.4-10.5) reported sexual violence by armed groups
      compared to 39.0% (95% CI 25.6-54.2) of female refugee heads of household. Women
      who knew how to add and subtract were less likely to report sexual violence
      during their lifetime (OR 0.16, 95% CI 0.08-0.34). Sexual violence is common
      among refugees and host population in Eastern Cameroon. Most often, perpetrators
      are partners/husbands or armed groups.

PMID- 22621465
TI  - Pharmacokinetics of a new immediate-release methadone tablet formulation with
      decreased in vitro solubility.
AB  - BACKGROUND: A new tablet formulation of methadone was developed with unique
      physicochemical properties, allowing for decreased solubility in aqueous
      solutions in in vitro studies. It was unknown whether this newly developed
      formulation would affect its bioavailability compared with the currently
      available formulation of methadone. OBJECTIVES: The objective of this study was
      to further examine the in vitro solubility of the new methadone formulation, and
      to evaluate and compare the relative bioavailability and pharmacokinetics to the
      previous reference formulation after a single oral dose administration under
      fasting conditions. METHODS: In vitro comparative dissolution for the new
      methadone formulation and the previous reference formulation was conducted. A
      randomized, single-dose, blinded, two-period, two-sequence, crossover
      pharmacokinetic study was performed in 24 healthy volunteers under fasting
      conditions. RESULTS: The new methadone formulation demonstrated a 30-40% decrease
      in solubility over 30 minutes compared with the previous reference formulation at
      the highest dose; all other doses also showed decreased in vitro solubility. The
      pharmacokinetic parameters determined were: maximum plasma drug concentration
      (C(max)) of 38.1 ng/mL; time to reach C(max) (t(max)) of 2.80 hours; mean area
      under the plasma concentration-time curve (AUC) from time zero to 72 hours
      (AUC(72)) of 1043 ng . h/mL; mean AUC from time zero to infinity (AUC(infinity))
      of 1430 ng . h/mL; mean elimination rate constant (k(e)) of 0.0206 hours(-1); and
      mean elimination half-life (t(1/2)) of 36.7 hours. These values are statistically
      equivalent to the previous reference formulation of methadone. CONCLUSION: This
      study provides the first complete set of pharmacokinetic data on a novel
      methadone formulation. The formulation demonstrates decreased in vitro solubility
      while providing equivalent plasma methadone levels compared with the previous
      formulation.

PMID- 22621467
TI  - Effect of thermal annealing on the kinetics of rehydroxylation of Eu3+:La2O3
      nanocrystals.
AB  - Europium-doped lanthanum oxide (5 mol % Eu(3+):La(2)O(3)) was prepared by
      calcining europium-doped lanthanum hydroxide (5 mol % Eu(3+):La(OH)(3))
      previously synthesized by a simple hydrothermal method. Interestingly, we
      observed different emission Eu(3+) signatures depending on the phase of the host
      (lanthanum oxide or hydroxide) by cathodoluminescence. Taking into account that
      lanthanum oxide easily rehydroxylates in air, for the first time, we report the
      use of cathodoluminiscence as a novel characterization technique to follow the
      lanthanum oxide rehydroxylation reaction versus time according to different
      annealing procedures. Additionally, differential thermal-thermogravimetric
      analysis, infrared spectroscopy, and X-ray diffraction techniques were used to
      identify the phases formed from the Eu(3+):La(OH)(3) depending on temperature and
      to study the evolution of La(2)O(3) to La(OH)(3) versus time. The results showed
      that the higher the temperature and the longer the annealing time, the higher the
      resistance to rehydroxylation of the Eu(3+):La(2)O(3) sample.

PMID- 22621468
TI  - (Ga1-xZnx)(N1-xOx) nanocrystals: visible absorbers with tunable composition and
      absorption spectra.
AB  - Bulk oxy(nitride) (Ga(1-x)Zn(x))(N(1-x)O(x)) is a promising photocatalyst for
      water splitting under visible illumination. To realize its solar harvesting
      potential, it is desirable to minimize its band gap through synthetic control of
      the value of x. Furthermore, improved photochemical quantum yields may be
      achievable with nanocrystalline forms of this material. We report the synthesis,
      structural, and optical characterization of nanocrystals of (Ga(1-x)Zn(x))(N(1
      x)O(x)) with the values of x tunable from 0.30 to 0.87. Band gaps decreased from
      2.7 to 2.2 eV over this composition range, which corresponded to a 260% increase
      in the fraction of solar photons that could be absorbed by the material. We
      achieved nanoscale morphology and compositional control by employing mixtures of
      ZnGa(2)O(4) and ZnO nanocrystals as synthetic precursors that could be converted
      to (Ga(1-x)Zn(x))(N(1-x)O(x)) under NH(3). The high quality of the resulting
      nanocrystals is encouraging for achieving photochemical water-splitting rates
      that are competitive with internal carrier recombination pathways.

PMID- 22621609
TI  - Contrast-induced nephropathy: attributable incidence and potential harm.
AB  - Contrast-induced nephropathy is a common form of hospital-acquired acute kidney
      injury. Incidence is low in patients with normal renal function but increases in
      high-risk patients. Patients with contrast-induced nephropathy have higher in
      hospital complication rates and mortality. Critically ill patients have been
      assumed to be a high-risk group for contrast-induced nephropathy. In the previous
      issue of Critical Care, Cely and colleagues showed an unexpectedly low incidence
      of contrast-induced nephropathy in critically ill patients receiving radiographic
      contrast material for computerized tomography. We should note that it is
      difficult to establish the true frequency and impact of the contrast
      nephrotoxicity because of many other causes for acute kidney injury in this
      population. Moreover, the impact on long-term kidney function and the possible
      effect of this insult on the recovery of renal function when associated with
      other causes of acute kidney injury are unknown. 

PMID- 22621611
TI  - HLA in patients with chronic spontaneous urticaria who are positive for anti
      thyroid antibodies.

PMID- 22621612
TI  - C-GATE - catalogue of genes affected by transposable elements.
AB  - BACKGROUND: Functional regulatory sequences are present in many transposable
      element (TE) copies, resulting in TEs being frequently exapted by host genes.
      Today, many examples of TEs impacting host gene expression can be found in the
      literature and we believe a new catalogue of such exaptations would be useful for
      the field. FINDINGS: We have established the catalogue of genes affected by
      transposable elements (C-GATE), which can be found at
      https://sites.google.com/site/tecatalog/. To date, it holds 221 cases of
      biologically verified TE exaptations and more than 10,000 in silico TE-gene
      partnerships. C-GATE is interactive and allows users to include missed or new TE
      exaptation data. C-GATE provides a graphic representation of the entire library,
      which may be used for future statistical analysis of TE impact on host gene
      expression. CONCLUSIONS: We hope C-GATE will be valuable for the TE community but
      also for others who have realized the role that TEs may have in their research.

PMID- 22621613
TI  - Dissociation of dysfunctional breathing and odour intolerance among adults in a
      general-population study.
AB  - BACKGROUND: Many patients present with a mixture of respiratory problems such as
      shortness of breath, heavy breathing, coughing and odour intolerance. If these
      patients are diagnosed as asthma, it might sometimes be a false diagnosis.
      Concepts such as sensory hyperreactivity, hyperventilation, asthma-like symptoms,
      odour intolerance and dysfunctional breathing are used to refer to these
      patients. Non-respiratory symptoms such as headache, fatigue and bloating are
      sometimes also part of the clinical picture. Our aim was to use factor analysis
      to increase our understanding of breathing-related symptoms in a general
      population frame. METHODS: A respiratory questionnaire was answered by 10 108
      subjects in a general-population sample. Items aiming to identify individuals
      with breathing-related symptoms and asthma were included. We used factor analysis
      with Varimax rotation to extract discriminatory components (i.e. groups of
      symptoms), based on the questionnaire items. The aim was to find groups of items
      (factors) as distinct as possible, still allowing overlap and showing the
      importance of each item in the separated factor. RESULTS: Five distinct factors
      were identified in the factor analysis, representing dysfunctional breathing,
      odour intolerance, asthma, bronchitis and a group with mixed symptoms,
      respectively. These five factors explained 55% of the variance. CONCLUSIONS:
      Based on our findings, we conclude that non-asthmatic breathing-related symptoms
      may be separated into at least two categories in a general population, odour
      intolerance and dysfunctional breathing. These two categories seem to be two
      distinct groups of subjects with breathing-related symptoms and may represent
      different clinical entities separated from asthma and bronchitis.

PMID- 22621614
TI  - Comparison of contrast in brightness mode and strain ultrasonography of glial
      brain tumours.
AB  - BACKGROUND: Image contrast between normal tissue and brain tumours may sometimes
      appear to be low in intraoperative ultrasound. Ultrasound imaging of strain is an
      image modality that has been recently explored for intraoperative imaging of the
      brain. This study aims to investigate differences in image contrast between
      ultrasound brightness mode (B-mode) images and ultrasound strain magnitude images
      of brain tumours. METHODS: Ultrasound radiofrequency (RF) data was acquired
      during surgery in 15 patients with glial tumours. The data were subsequently
      processed to provide strain magnitude images. The contrast in the B-mode images
      and the strain images was determined in assumed normal brain tissue and tumour
      tissue at selected regions of interest (ROI). Three measurements of contrast were
      done in the ultrasound data for each patient. The B-mode and strain contrasts
      measurements were compared using the paired samples t- test. RESULTS: The
      statistical analysis of a total of 45 measurements shows that the contrasts in
      the strain magnitude images are significantly higher than in the conventional
      ultrasound B-mode images (P < 0.0001). CONCLUSIONS: The results indicate that
      ultrasound strain imaging provides better discrimination between normal brain
      tissue and glial tumour tissue than conventional ultrasound B-mode imaging.
      Ultrasound imaging of tissue strain therefore holds the potential of becoming a
      valuable adjunct to conventional intraoperative ultrasound imaging in brain
      tumour surgery.

PMID- 22621616
TI  - Editorial--Letters in Applied Microbiology is changing!

PMID- 22621615
TI  - Iron solubility related to particle sulfur content in source emission and ambient
      fine particles.
AB  - The chemical factors influencing iron solubility (soluble iron/total iron) were
      investigated in source emission (e.g., biomass burning, coal fly ash, mineral
      dust, and mobile exhaust) and ambient (Atlanta, GA) fine particles (PM2.5).
      Chemical properties (speciation and mixing state) of iron-containing particles
      were characterized using X-ray absorption near edge structure (XANES)
      spectroscopy and micro-X-ray fluorescence measurements. Bulk iron solubility
      (soluble iron/total iron) of the samples was quantified by leaching experiments.
      Major differences were observed in iron solubility in source emission samples,
      ranging from low solubility (<1%, mineral dust and coal fly ash) up to 75%
      (mobile exhaust and biomass burning emissions). Differences in iron solubility
      did not correspond to silicon content or Fe(II) content. However, source emission
      and ambient samples with high iron solubility corresponded to the sulfur content
      observed in single particles. A similar correspondence between bulk iron
      solubility and bulk sulfate content in a series of Atlanta PM2.5 fine particle
      samples (N = 358) further supported this trend. In addition, results of linear
      combination fitting experiments show the presence of iron sulfates in several
      high iron solubility source emission and ambient PM2.5 samples. These results
      suggest that the sulfate content (related to the presence of iron sulfates and/or
      acid-processing mechanisms by H(2)SO(4)) of iron-containing particles is an
      important proxy for iron solubility.

PMID- 22621617
TI  - No association between IL12B gene polymorphisms and Graves' disease in the
      Chinese population.
AB  - BACKGROUND: Graves' disease (GD) is one of the most common autoimmune thyroid
      disorders and has a striking characteristic of female preponderance. OBJECTIVE:
      The main objective of this study was to investigate whether IL12B gene
      polymorphisms were associated with either GD itself or with gender bias in GD.
      METHODS: GD patients (151 males, 97 females) and 211 healthy control subjects
      without antithyroid autoantibodies or a family history of autoimmune disorders
      were recruited for this study. The G/C polymorphism (rs6887695) of the IL12B gene
      was analyzed using the polymerase chain reaction-restriction fragment length
      polymorphism, and the deletion and insertion polymorphism (rs41292470) in the
      IL12B promoter was detected after polyacrylamide gel electrophoresis-silver
      staining method. RESULTS: There was no significant difference between GD patients
      and normal subjects, and no differences in frequencies of genotypes or alleles of
      either polymorphism between male and female GD subjects. CONCLUSION: We conclude
      that these IL12B gene polymorphisms were not associated with sex bias in GD and
      do not confer susceptibility to Graves' disease (GD) in the Chinese population.

PMID- 22621618
TI  - Long-term well-being after surgical or conservative treatment of severe vulvar
      vestibulitis.
AB  - OBJECTIVE: To compare long-term well-being of women who needed surgery or did not
      need surgery in the treatment of severe vulvar vestibulitis syndrome. We also
      attempted to identify factors explaining differences in the treatment response.
      DESIGN: An observational case-control study. SETTING: University Hospital Vulva
      clinic. POPULATION: Sixty-six women diagnosed with severe vulvar vestibulitis and
      treated initially by conservative management during 1994-2005. Thirty-nine women
      did not respond and underwent posterior vestibulectomy and 27 were managed
      without surgery. METHODS: Baseline patient characteristics, degree of
      dyspareunia, and details of management were collected from hospital charts. At
      the follow-up visit current dyspareunia, sexual well-being, somatic and mental
      health, and social support were analyzed. Vestibular tenderness was measured by
      swab-touch test. MAIN OUTCOME MEASURES: Visual analogue scale for dyspareunia,
      sexual well-being, vestibular tenderness, and overall patient satisfaction at
      follow-up. RESULTS: Dyspareunia decreased significantly in both groups. The
      visual analogue scale decreased 66.7% in the surgery group and 78.1% in the
      conservative treatment group (p= 0.407). Posterior swab-touch test was negative
      more frequently after vestibulectomy. Long-term sexual well-being did not differ
      between the two groups. Overall, 89% of the women in both groups were satisfied
      with the treatment. Women with atopic skin problems were less likely to need
      surgery (odds ratio 0.2; 95% confidence interval 0.1-0.7). CONCLUSION: Women with
      severe vulvar vestibulitis syndrome who do not respond to conservative management
      achieve good long-term well-being and decrease of dyspareunia by posterior
      vestibulectomy. The response is comparable to that achieved by conservative
      management among women who do not need surgery.

PMID- 22621619
TI  - Intrathecal medications in post-herpetic neuralgia.

PMID- 22621620
TI  - Antitumor activity of human gammadelta T cells transducted with CD8 and with T
      cell receptors of tumor-specific cytotoxic T lymphocytes.
AB  - The difficulty in the induction and preparation of a large number of autologous
      tumor-specific cytotoxic T lymphocytes (CTL) from individual patients is one of
      major problems in their application to adoptive immunotherapy. The present study
      tried to establish the useful antitumor effectors by using gammadelta T cells
      through tumor-specific TCRalphabeta genes transduction, and evaluated the
      efficacy of their adoptive transfer in a non-obese diabetic/severe combined
      immunodeficiency (NOD/SCID) mice model. The TCRalphabeta gene was cloned from the
      HLA-B15-restricted CTL clone specific of the Kita-Kyushu Lung Cancer antigen-1
      (KK-LC-1). The cloned TCRalphabeta as well as the CD8 gene were transduced into
      gammadelta T cells induced from peripheral blood lymphocytes (PBL). Cytotoxic T
      lymphocyte activity was examined using a standard 4 h (51) Cr release assay. Mice
      with a xenotransplanted tumor were treated with an injection of effector cells.
      Successful transduction of TCRalphabeta was confirmed by the staining of KK-LC-1
      specific tetramers. The gammadelta T cells transduced with TCRalphabeta and CD8
      showed CTL activity against the KK-LC-1-positive lung cancer cell line in a HLA
      B15-restricted manner. Adoptive transfer of the effector cells in a mice model
      resulted in marked growth suppression of KK-LC-1- and HLA-B15-positive
      xenotransplanted tumors. Co-transducing TCRalphabeta and CD8 into gammadelta T
      cells yielded the same antigen-specific activity as an original CTL in vitro and
      in vivo. The TCRalphabeta gene transduction into gammadelta T cells is a
      promising strategy for developing new adoptive immunotherapy.

PMID- 22621621
TI  - Survey of patient and public perceptions of electronic health records for
      healthcare, policy and research: study protocol.
AB  - BACKGROUND: Immediate access to patients' complete health records via electronic
      databases could improve healthcare and facilitate health research. However, the
      possible benefits of a national electronic health records (EHR) system must be
      balanced against public concerns about data security and personal privacy.
      Successful development of EHR requires better understanding of the views of the
      public and those most affected by EHR: users of the National Health Service. This
      study aims to explore the correlation between personal healthcare experience
      (including number of healthcare contacts and number and type of longer term
      conditions) and views relating to development of EHR for healthcare, health
      services planning and policy and health research. METHODS/DESIGN: A multi-site
      cross-sectional self-complete questionnaire designed and piloted for use in
      waiting rooms was administered to patients from randomly selected outpatients'
      clinics at a university teaching hospital (431 beds) and general practice
      surgeries from the four primary care trusts within the catchment area of the
      hospital. All patients entering the selected outpatients clinics and general
      practice surgeries were invited to take part in the survey during August
      September 2011. Statistical analyses will be conducted using descriptive
      techniques to present respondents' overall views about electronic health records
      and logistic regression to explore associations between these views and
      participants' personal circumstances, experiences, sociodemographics and more
      specific views about electronic health records. DISCUSSION: The study design and
      implementation were successful, resulting in unusually high response rates and
      overall recruitment (85.5%, 5336 responses). Rates for face-to-face recruitment
      in previous work are variable, but typically lower (mean 76.7%, SD 20). We
      discuss details of how we collected the data to provide insight into how we
      obtained this unusually high response rate.

PMID- 22621622
TI  - Highly enantioselective regiodivergent allylic alkylations of MBH carbonates with
      phthalides.
AB  - Phthalides were used for the first time in the allylic alkylation reactions with
      MBH carbonates for the creation of chiral 3,3-disubstituted phthalides. Highly
      enantioselective regiodivergent synthesis of gamma-selective or beta-selective
      allylic alkylation products was achieved by employing bifunctional chiral
      phosphines or multifunctional tertiary amine-thioureas as the catalyst,
      respectively. It was demonstrated that proper selection of catalysts and reaction
      conditions would differentiate an S(N)2'-S(N)2' pathway and an addition
      elimination process, yielding different regioisomers of the allylic alkylation
      products in a highly enantiomerically pure form.

PMID- 22621623
TI  - Antimetastatic effect of sulfamate carbonic anhydrase IX inhibitors in breast
      carcinoma xenografts.
AB  - A panel of compounds belonging to the underexposed sulfamate class of carbonic
      anhydrase (CA, EC 4.2.1.1) inhibitors was generated that displayed high
      specificity at nanomolar levels for the tumor-associated CA IX/XII isoforms.
      Three of the specific CA IX/XII inhibitors showed a positive response in in vitro
      assays for tumor cell migration and spreading. One of them, 4-(3'-(3",5"
      dimethylphenyl)ureido)phenyl sulfamate (S4), was taken forward into the
      orthotopic MDA-MB-231 (breast carcinoma) model in mice. Treatment with a 10 mg/kg
      maintenance dosage of S4 given daily on a "5 days on, 2 days off" regimen reduced
      metastatic tumor burden in the lung while not affecting primary tumor growth or
      mouse condition. CA inhibitors of the sulfamate class specifically targeting the
      tumor-associated isoforms are potential candidates in antimetastatic therapy.

PMID- 22621624
TI  - A rare cause of massive hepatomegaly.

PMID- 22621625
TI  - Sharing the care to improve access to primary care.

PMID- 22621626
TI  - Aspirin for preventing the recurrence of venous thromboembolism.
AB  - BACKGROUND: About 20% of patients with unprovoked venous thromboembolism have a
      recurrence within 2 years after the withdrawal of oral anticoagulant therapy.
      Extending anticoagulation prevents recurrences but is associated with increased
      bleeding. The benefit of aspirin for the prevention of recurrent venous
      thromboembolism is unknown. METHODS: In this multicenter, investigator-initiated,
      double-blind study, patients with first-ever unprovoked venous thromboembolism
      who had completed 6 to 18 months of oral anticoagulant treatment were randomly
      assigned to aspirin, 100 mg daily, or placebo for 2 years, with the option of
      extending the study treatment. The primary efficacy outcome was recurrence of
      venous thromboembolism, and major bleeding was the primary safety outcome.
      RESULTS: Venous thromboembolism recurred in 28 of the 205 patients who received
      aspirin and in 43 of the 197 patients who received placebo (6.6% vs. 11.2% per
      year; hazard ratio, 0.58; 95% confidence interval [CI], 0.36 to 0.93) (median
      study period, 24.6 months). During a median treatment period of 23.9 months, 23
      patients taking aspirin and 39 taking placebo had a recurrence (5.9% vs. 11.0%
      per year; hazard ratio, 0.55; 95% CI, 0.33 to 0.92). One patient in each
      treatment group had a major bleeding episode. Adverse events were similar in the
      two groups. CONCLUSIONS: Aspirin reduced the risk of recurrence when given to
      patients with unprovoked venous thromboembolism who had discontinued
      anticoagulant treatment, with no apparent increase in the risk of major bleeding.
      (Funded by the University of Perugia and others; WARFASA ClinicalTrials.gov
      number, NCT00222677.).

PMID- 22621627
TI  - Effectiveness of long-acting reversible contraception.
AB  - BACKGROUND: The rate of unintended pregnancy in the United States is much higher
      than in other developed nations. Approximately half of unintended pregnancies are
      due to contraceptive failure, largely owing to inconsistent or incorrect use.
      METHODS: We designed a large prospective cohort study to promote the use of long
      acting reversible contraceptive methods as a means of reducing unintended
      pregnancies in our region. Participants were provided with reversible
      contraception of their choice at no cost. We compared the rate of failure of long
      acting reversible contraception (intrauterine devices [IUDs] and implants) with
      other commonly prescribed contraceptive methods (oral contraceptive pills,
      transdermal patch, contraceptive vaginal ring, and depot medroxyprogesterone
      acetate [DMPA] injection) in the overall cohort and in groups stratified
      according to age (less than 21 years of age vs. 21 years or older). RESULTS:
      Among the 7486 participants included in this analysis, we identified 334
      unintended pregnancies. The contraceptive failure rate among participants using
      pills, patch, or ring was 4.55 per 100 participant-years, as compared with 0.27
      among participants using long-acting reversible contraception (hazard ratio after
      adjustment for age, educational level, and history with respect to unintended
      pregnancy, 21.8; 95% confidence interval, 13.7 to 34.9). Among participants who
      used pills, patch, or ring, those who were less than 21 years of age had a risk
      of unintended pregnancy that was almost twice as high as the risk among older
      participants. Rates of unintended pregnancy were similarly low among participants
      using DMPA injection and those using an IUD or implant, regardless of age.
      CONCLUSIONS: The effectiveness of long-acting reversible contraception is
      superior to that of contraceptive pills, patch, or ring and is not altered in
      adolescents and young women. (Funded by the Susan Thompson Buffet Foundation.).

PMID- 22621628
TI  - Anti-CD20 antibody therapy for B-cell lymphomas.

PMID- 22621629
TI  - Images in clinical medicine. Meconium-like ileus in cystic fibrosis.

PMID- 22621630
TI  - Case records of the Massachusetts General Hospital. Case 16-2012. A 32-year-old
      woman with HER2-positive breast cancer.

PMID- 22621631
TI  - Aspirin and the prevention of venous thromboembolism.

PMID- 22621633
TI  - Ruxolitinib for myelofibrosis.

PMID- 22621634
TI  - Ruxolitinib for myelofibrosis.

PMID- 22621635
TI  - Ruxolitinib for myelofibrosis.

PMID- 22621637
TI  - Abscopal effect in a patient with melanoma.

PMID- 22621639
TI  - Dysfunction of the diaphragm.

PMID- 22621640
TI  - Dysfunction of the diaphragm.

PMID- 22621641
TI  - BRAF inhibition in refractory hairy-cell leukemia.

PMID- 22621642
TI  - Images in clinical medicine. Aquagenic wrinkling of palms in cystic fibrosis.

PMID- 22621643
TI  - Topical ocular anaesthetic abuse in a contact lens wearer: a case of microbial
      keratitis.
AB  - We describe the abuse of a topical ocular anaesthetic in a contact lens wearer
      who developed microbial keratitis.

PMID- 22621644
TI  - Paediatric follow-up of haemodynamically insignificant congenital cardiac
      lesions.
AB  - AIM: To describe the prevailing follow-up of haemodynamically insignificant
      congenital cardiac lesions (HICCL) in the UK. To suggest a rationalisation of
      follow-up based on the known natural history of these lesions. METHODS: An
      internet-based survey of 170 paediatric cardiologists and general paediatricians
      with an interest in cardiology in the UK. Five scenarios concerning common HICCL
      were presented: ventricular and atrial septal defects, patent foramen ovale, mild
      pulmonary stenosis and persistent ductus arteriosus. RESULTS: There were 52
      respondents. There was a broad range of beliefs and practices. However, there
      were tendencies to discharge children with a patent foramen ovale and follow
      patients with all other lesions, often on a relatively frequent basis.
      CONCLUSIONS: The increasingly sensitive and advanced nature of echocardiography
      and the subsequent reliance upon it may be contributing to unnecessarily frequent
      review of HICCL and a reluctance to discharge patients. In the majority of
      patients with HICCL, no more than two assessments of HICCL are required after 2
      years of age - once in late childhood and once near full growth.

PMID- 22621645
TI  - Costs of in-patient treatment for endometriosis in Germany 2006: an analysis
      based on the G-DRG-Coding.
AB  - OBJECTIVE: The aim of this study was to estimate the financial burden of in
      patients costs for endometriosis treatment in Germany in 2006. METHODS: Data from
      a national in-patient database for women of reproductive age who were admitted
      for surgical treatment for endometriosis were analysed retrospectively. The
      number and type of hospital admissions involving surgical interventions for
      endometriosis were identified, and the costs of these hospitalizations to funding
      bodies in Germany were estimated using the diagnosis-related group reimbursement
      rates. RESULTS: A total of 20,835 patients were admitted to hospital for
      endometriosis treatment in Germany in 2006 (1.27 per 1,000 women in reproductive
      age). The average cost per patient was estimated at 3,056.21 ?. The total in
      patient costs for endometriosis treatment in 2006 were estimated at 40,708,716.26
      ?. The surgical procedure most often performed in treating endometriosis was
      hysterectomy (in 24.70% of cases). CONCLUSION: The burden of admissions and the
      economic impact associated with the inpatients treatment of endometriosis in
      Germany is substantial. The results presented here may enable those responsible
      in the field of medicine and health-care policy to improve the allocation of
      resources and manage expenses on a more sustained basis.

PMID- 22621646
TI  - Traumatic lingual ulceration in a newborn: Riga-Fede disease.
AB  - Riga Fede disease is a reactive mucosal disease as a result of repetitive trauma
      of the tongue by the anterior primary teeth during forward and backward movement.
      Although the aspect of the lesion might be impressive, its nature is relatively
      benign. The history and clinical features are most often so typical that there is
      seldom a need for addititonal histopathological examination. Riga Fede disease
      can most often be treated with conservative measures only.Beside the presentation
      of a six-month-old boy with Riga Fede disease, the literature has been reviewed
      as well. From this review it can be concluded that Riga Fede disease is almost
      exclusively restricted to the tongue, occurs soon after birth when associated
      with (neo)natal teeth, has a male predilection, and is in one quarter of the
      cases associated with neurologic disorders. In the later case, Riga Fede disease
      develops after the age of 6 months.

PMID- 22621654
TI  - Malignant melanoma in childhood and adolescence.

PMID- 22621652
TI  - Electrochemistry of platinum(II) porphyrins: effect of substituents and pi
      extension on redox potentials and site of electron transfer.
AB  - Fourteen platinum(II) porphyrins with different pi-conjugated macrocycles and
      different electron-donating or electron-withdrawing substituents were
      investigated as to their electrochemical and spectroscopic properties in
      nonaqueous media. Eight compounds have the formula (Ar(4)P)Pt(II), where Ar(4)P =
      the dianion of a tetraarylporphyrin, while six have pi-extented macrocycles with
      four beta,beta'-fused benzo or naphtho groups and are represented as (TBP)Pt(II)
      and (TNP)Pt(II) where TBP and TNP are the dianions of tetrabenzoporphyrin and
      tetranaphthoporphyrin, respectively. Each Pt(II) porphyrin undergoes two
      reversible one-electron reductions and one to three reversible one-electron
      oxidations in nonaqueous media. These reactions were characterized by cyclic
      voltammetry, UV-visible thin-layer spectroelectrochemistry and in some cases by
      ESR spectroscopy. The two reductions invariably occur at the conjugated pi-ring
      system to yield relatively stable Pt(II) pi-anion radicals and dianions. The
      first oxidation leads to a stable pi-cation radical for each investigated
      porphyrin; but in the case of tetraarylporphyrins containing electron-withdrawing
      substituents, the product of the second oxidation may undergo an internal
      electron transfer to give a Pt(IV) porphyrin with an unoxidized macrocycle. The
      effects of macrocycle structure on UV-visible spectra, oxidation/reduction
      potentials, and site of electron transfer are discussed.

PMID- 22621655
TI  - Direct nanomechanical measurement of an anchoring transition in a nematic liquid
      crystal subject to hybrid anchoring conditions.
AB  - We have used a surface forces apparatus to measure the normal force between two
      solid curved surfaces confining a film of nematic liquid crystal (5CB, 4'-n
      pentyl-4-cyanobiphenyl) under hybrid planar-homeotropic anchoring conditions.
      Upon reduction of the surface separation D, we measured an increasingly repulsive
      force in the range D = 35-80 nm, reaching a plateau in the range D = 10-35 nm,
      followed by a short-range oscillatory force at D < 5 nm. The oscillation period
      was comparable to the cross-sectional diameter of the liquid crystal molecule and
      characteristic of a configuration with the molecules parallel to the surfaces.
      These results show that the director field underwent a confinement-induced
      transition from a splay-bend distorted configuration at large D, which produces
      elastic repulsive forces, to a uniform planar nondegenerate configuration with
      broken homeotropic anchoring, which does not produce additional elastic forces as
      D is decreased. These findings, supported by measurements of the birefringence of
      the confined film at different film thicknesses, provide the first direct
      observation of an anchoring transition on the nanometer scale.

PMID- 22621656
TI  - New strategies to manage complicated pleural effusions.
AB  - BACKGROUND: More than 30% of patients with pleural infection either die or
      require surgery. Drainage of infected fluid is the key to successful treatment,
      but intrapleural fibrinolytic therapy did not improve outcomes in an earlier,
      large, randomized trial therapy (Multicenter Intrapleural Sepsis Trial [MIST1]).
      METHODS: Objective: To evaluate the efficacy and safety of intrapleural DNase
      alone, alteplase alone, or the combination of both, to improve pleural drainage.
      Design: Multicenter, double-blind, double-dummy, 2 * 2 factorial randomized
      trial. Setting: Eleven centers in the United Kingdom (UK). Subjects: Adult
      patients (mean age 59 years, 72% men), who had clinical evidence of infection,
      and pleural fluid that had macroscopic purulence, a positive culture or Gram
      stain for bacteria, or a pH < 7.2. Intervention: Patients were assigned to 1 of
      the 4 study interventions for 3 days: double placebo, intrapleural tissue
      plasminogen activator (t-PA) and DNase, t-PA and placebo, or DNase and placebo.
      Outcomes: The primary outcome was the change in pleural opacity, measured as the
      percentage of the hemithorax occupied by effusion, on chest radiography on day 7
      as compared with day 1. Secondary outcomes included referral for surgery,
      duration of hospital stay, and adverse events. RESULTS: The mean (+/- SD) change
      in pleural opacity was greater in the t-PA-DNase group than in the placebo group
      (-29.5 +/- 23.3% vs. -17.2 +/- 19.6%; difference, -7.9%; 95% confidence interval
      [CI], -13.4 to -2.4; P = 0.005). The change observed with t-PA alone and with
      DNase alone (-17.2 +/- 24.3 and -14.7 +/- 16.4%, respectively) was not
      significantly different from that observed with placebo. The frequency of
      surgical referral at 3 months was lower in the t-PA-DNase group than in the
      placebo group (2 of 48 patients [4%] vs. 8 of 51 patients [16%]; odds ratio for
      surgical referral, 0.17; 95% CI, 0.03 to 0.87; P = 0.03) but was greater in the
      DNase group (18 of 46 patients [39%]) than in the placebo group (odds ratio,
      3.56; 95% CI, 1.30 to 9.75; P = 0.01). Combined t-PA-DNase therapy was associated
      with a reduction in the hospital stay, as compared with placebo (difference, -6.7
      days; 95% CI, -12.0 to -1.9; P = 0.006). Hospital stay with either agent alone
      was not significantly different from that with placebo. The frequency of adverse
      events did not differ significantly among the groups. CONCLUSIONS: Intrapleural t
      PA-DNase therapy improved fluid drainage in patients with pleural infection and
      reduced the frequency of surgical referral and the duration of hospital stay.
      Treatment with DNase alone or t-PA alone was ineffective.

PMID- 22621657
TI  - Transformation of 1H-benzotriazole by ozone in aqueous solution.
AB  - Recent studies have shown that 1H-benzotriazole is a widespread contaminant of
      wastewater and surface water. Although disinfection by ozone has been shown to
      efficiently remove this compound, the transformation products have not been
      identified. To that end, the reaction of ozone with 1H-benzotriazole in aqueous
      solution has been studied in real time employing quadrupole time-of-flight mass
      spectrometry (Q-TOF MS) and negative electrospray ionization. The transformation
      products have been identified by calculating their empirical formulas using
      accurate mass measurements, and further confirmed by performing the reaction with
      stable isotope-labeled 1H-benzotriazole and measuring product ion spectra. Stable
      reaction products were distinguished from transient species by plotting their
      extracted mass profiles. The products that resulted from ozone and hydroxyl
      radicals in the reaction were qualitatively identified by modifying the
      conditions to either promote the formation of hydroxyl radicals, or to scavenge
      them. Based on experimental evidence, a mechanism for the direct reaction between
      ozone and 1H-benzotriazole is proposed that results in the formation of 1H-1,2,3
      triazole-4,5-dicarbaldehyde, which has an empirical formula of C(4)H(3)O(2)N(3).
      Lastly, it was confirmed that the same transformation products formed in surface
      water and tertiary-treated wastewater, although they were observed to degrade at
      higher ozone doses.

PMID- 22621658
TI  - Foot placement patterns of female rollator users with multiple sclerosis in the
      community.
AB  - PURPOSE: The objective of this study was to investigate the relationship between
      medio-lateral foot placement characteristics and environmental context when
      individuals with Multiple Sclerosis (MS) walk with a rollator (four-wheeled
      walker). METHOD: Ten women diagnosed with MS, who used rollators regularly,
      participated in this study. First, a rollator-based technique of calculating step
      width (SW) was validated in this patient population by comparing the output of an
      instrumented rollator (iWalker) to a laboratory-based Vicon Motion Capture
      System. Secondly, the iWalker-based technique was used to calculate the
      participants' SW and SW variability as they used the iWalker in four common
      outdoor community environments. RESULTS: There was a strong level of agreement
      between the iWalker and Vicon SW calculations, with an intra-class correlation
      coefficient of 0.993 and a root-mean-square difference of 0.71 cm. Furthermore,
      SW variability (P = 0.002), but not SW (P = 0.288), was influenced by the walking
      environment (i.e. between the in-lab vs. up-ramp and up-ramp vs. down-ramp
      conditions). CONCLUSIONS: Foot placement variability appears to be influenced by
      the walking environment of MS patients. Therefore, an enhanced understanding of
      walker-user interactions in relation to the environment must be established in
      order to improve mobility.

PMID- 22621659
TI  - Immunohistochemical staining of surfactant proteins A and B in skin of psoriatic
      patients before and after narrow-band UVB phototherapy.
AB  - BACKGROUND: Psoriasis is a chronic inflammatory disorder that is mediated by
      elements of the innate and adaptive immune systems. Surfactant proteins (SPs)
      play an important role in host defense mechanisms. They are thought to have a
      potential role in some inflammatory skin diseases including psoriasis. OBJECTIVE:
      The aim of the study was to evaluate SP-A and SP-B immunohistochemical staining
      in skin of psoriatic patients before and after narrow-band UV radiation type B
      (NB-UVB) phototherapy. STUDY DESIGN: Immunohistochemical staining for SP-A and SP
      B was performed on tissues from 20 psoriatic patients before and after NB-UVB.
      Results were compared with the degree of improvement assessed by the Psoriasis
      Area and Severity Index (PASI) and duration of treatment. RESULTS: In unaffected
      skin, SP-A and SP-B were restricted to the basal layer; however, in psoriatic
      skin, they appeared in suprabasal layers in 80% and 85% of cases, respectively.
      Dermal inflammatory cells showed SP-A in 11 cases (55%) and SP-B in only one case
      (5%). After treatment by NB-UVB, SP-A and SP-B staining showed predilection to
      the basal layer. Absence of SP-A staining in suprabasal layers after NB-UVB
      therapy was correlated to better response to therapy (p=0.003) and shorter
      duration of treatment (p<0.0001). CONCLUSIONS: SP-A and SP-B positivity is
      increased in psoriatic skin and reduced after NB-UVB therapy. Absence of SP-A in
      suprabasal layers after NB-UVB therapy is associated with better response and
      shorter duration of treatment.

PMID- 22621660
TI  - Gastrointestinal symptoms before and during menses in women with IBD.
AB  - BACKGROUND: It is believed that women with inflammatory bowel disease (IBD) have
      heightened symptoms around their menses. However, there is little information
      regarding normative changes and which symptoms emerge in relation to menses. AIM:
      To determine the relationship between gastrointestinal and other symptoms and
      menses in a population-based cohort of women with IBD vs. healthy women. METHODS:
      Women enrolled in the University of Manitoba IBD Research Registry who were
      between 18 and 65 years were mailed a survey. A control group of adult women were
      recruited through out-patient gynaecology clinics. Participants were asked to
      consider their menstrual periods in the recent several months and report on
      symptoms 1-5 days prior to and during the days of their menses. RESULTS: There
      were 151 premenopausal women with Crohn's disease (CD), 87 with ulcerative
      colitis (UC) and 156 premenopausal controls. Mean age of menses onset was similar
      in all three cohorts and the percentage in each group with regular menstrual
      periods was similar. Premenstrually, abdominal pain was less commonly reported in
      UC (36.8%) than CD (51%, P = 0.034) and controls (57.6%, P = 0.002).
      Premenstrually, and during menses diarrhoea was more commonly reported in CD
      (47.7% and 59.6% respectively) than UC (26.4% P = 0.001 and 42.5%, P = 0.01
      respectively) and controls (24.4%, P < 0.0001 and 28.2%, P < 0.0001
      respectively). Premenstrually, women with CD (46%) vs. UC (26%) were more likely
      to report worsening of their IBD symptoms (P = 0.0007), but there was no
      difference between CD (47%) and UC (39%) for reporting worsening during menses (P
      = 0.24). CONCLUSIONS: Compared to healthy women, women with IBD had similar
      symptom experiences premenstrually, except that those with CD were more likely to
      have increased diarrhoea premenstrually. During menses, women with CD or UC were
      more likely to experience diarrhoea than healthy controls.

PMID- 22621662
TI  - Writing for publication: what about case reports?

PMID- 22621661
TI  - Pax3( GFP ) , a new reporter for the melanocyte lineage, highlights novel aspects
      of PAX3 expression in the skin.
AB  - The paired box gene 3 (Pax3) is expressed during pigment cell development. We
      tested whether the targeted allele Pax3(GFP)  can be used as a reporter gene for
      pigment cells in the mouse. We found that enhanced green fluorescent protein
      (GFP) can be seen readily in every melanoblast and melanocyte in the epidermis
      and hair follicles of Pax3(GFP/+)  heterozygotes. The GFP was detected at all
      differentiation stages, including melanocyte stem cells. In the dermis, Schwann
      cells and nestin-positive cells of the piloneural collars resembling the nestin
      positive hair follicle multipotent stem cells exhibited a weaker GFP signal.
      Pigment cells could be purified by fluorescent activated cell sorting and grown
      in vitro without feeder cells, giving pure cultures of melanocytes. The Schwann
      cells and nestin-positive cells of the piloneural collars were FACS-isolated
      based on their weak expression of GFP. Thus Pax3(GFP)  can discriminate distinct
      populations of cells in the skin.

PMID- 22621663
TI  - The perception of role conflict in sexual assault nursing and its effects on care
      delivery.
AB  - The role of the sexual assault nurse examiner (SANE) combines two once-distinct
      roles--nursing and forensic science. Therefore, there is a potential for role
      conflict that may impact SANEs as well as the care they deliver. In this
      qualitative study, 14 SANEs were interviewed regarding their roles. Most
      participants did not endorse role conflict; however, most also provided examples
      of conflict between their roles as nurses and their roles as evidence collectors.
      Participants differed in their opinions of whether they were advocates or not in
      this capacity. SANEs talked about breaking the rules and caring about some
      patients even when they believed they were not supposed to. Several SANEs also
      talked about relying on the victim advocate to take the caring role-in effect,
      using advocates as proxy for the caring role SANEs would take in other nursing
      settings. The implications of these findings are discussed.

PMID- 22621664
TI  - Preventing sexual violence instead of just responding to it: students'
      perceptions of sexual violence resources on campus.
AB  - Rates of sexual assault of college students are higher than the national rates.
      Colleges are uniquely positioned to offer preventive education and support
      services to a high-risk group. This qualitative study examines students'
      perceptions of sexual violence resources and services. Seventy-eight female and
      male students, between 18 and 24 years old, belonging to various demographic
      groups, participated in one-to-one walking interviews on five diverse Midwest 2-
      and 4-year postsecondary campuses. Findings suggest that students are concerned
      with safety--students want more education regarding sexual violence--and they
      value services that offer protection from incidents of sexual violence on campus.
      Participants expressed mixed reactions to prevention education that combined
      sexual violence prevention with alcohol and drug use. Students shared positive
      views of the security measures on campus. They emphasized the importance of using
      varied mechanisms for sexual violence-related resource messaging and advised
      moving away from the pamphlet toward posters and online resources.
      Recommendations are offered to strengthen existing resources, such as prevention
      education and postassault interventions including sexual assault nurse examiner
      services, and to minimize barriers to access of sexual violence resources.

PMID- 22621665
TI  - Nurse practitioner knowledge of child sexual abuse in children with cognitive
      disabilities.
AB  - The purpose of this study was to describe the knowledge level of nurse
      practitioners regarding symptoms of child sexual abuse in children with cognitive
      disabilities. A total sample of 43 nurse practitioners from two professional
      nurse practitioner organizations was surveyed to assess child sexual abuse
      symptoms identification in intellectually disabled children using a revised
      edition of the Child Sexual Abuse Knowledge Survey. Data collected showed nurse
      practitioners have deficits in identifying various parts of prepubescent female
      genitalia. The majority of nurse practitioners did not check genitalia in regular
      physical exams, did not feel competent to perform this type of evaluation, and
      were not aware of their professional organizations' position regarding checking
      for child sexual abuse. When assessing a child with an intellectual disability,
      nurse practitioners must accurately assess physical symptoms and behaviors that
      could have resulted from sexual abuse. Examining children for sexual abuse is a
      required duty of the nurse practitioner as evidenced by the position statements
      of the various professional organizations and nurse practitioners must be aware
      of their required scope of practice.

PMID- 22621666
TI  - Sexual assault nurse examiners' perceptions of funding challenges faced by SANE
      programs: "it stinks".
AB  - Even though Sexual Assault Nurse Examiner (SANE) programs began over 30 years
      ago, and there is currently greater awareness of sexual violence, the question
      regarding the financial security of SANE prgrams remains a contemporary concern.
      Data from interviews with 40 SANEs', many of whom were also directors, from
      programs located in four states indicated that lack of funding continues to
      present challenges. Most (72%) directors revealed that there are problems with
      funding. Directors voiced concerns about program sustainability, as well as the
      ability to provide education in the community and training and continuing
      education opportunities for SANEs. Even though funding of programs is not the
      responsibility of SANEs not serving as directors, approximately one-third of
      regular SANEs were aware of budget cuts or financial struggles faced by their
      program. These SANEs also expressed concern about the sustainability of programs,
      the ability to train additional nurses, purchasing their equipment of choice, and
      lack of compensation. All suggestions for program improvements, directly or
      indirectly, required more funding.

PMID- 22621667
TI  - De-escalation and limit-setting in forensic mental health units.
AB  - Limit-setting and de-escalation are commonly used nursing interventions that are
      critical to the effective maintenance of the therapeutic milieu and the
      prevention and management of aggression in forensic mental health units. However,
      despite their purported importance, the techniques used in these interventions
      are rarely described. Further, these techniques are seldom based on empirical
      research or derived from a theory or model of aggression or interpersonal
      behavior. The purpose of this review is to examine the extant literature on limit
      setting and de-escalation and consider how these activities could be enhanced. In
      concluding, this review emphasizes the potential benefits of drawing upon (1) a
      model of aggressive behavior and (2) a theory and literature examining
      interpersonal behavior, to enhance limit-setting and de-escalation skills.

PMID- 22621668
TI  - Breastfeeding cessation and symptoms of anxiety and depression: a longitudinal
      cohort study.
AB  - BACKGROUND: Neonatal anxiety and depression and breastfeeding cessation are
      significant public health problems. There is an association between maternal
      symptoms of anxiety and depression and early breastfeeding cessation. In earlier
      studies, the causality of this association was interpreted both ways; symptoms of
      anxiety and depression prepartum significantly impacts breastfeeding, and
      breastfeeding cessation significantly impacts symptoms of anxiety and
      depression.First, we aimed to investigate whether breastfeeding cessation is
      related to an increase in symptoms of anxiety and depression from pregnancy to
      six months postpartum. Second, we also investigated whether the proposed symptom
      increase after breastfeeding cessation was disproportionately high for those
      women already suffering from high levels of anxiety and depression during
      pregnancy. METHODS: To answer these objectives, we examined data from 42 225
      women in the Norwegian Mother and Child Cohort Study (MoBa). Subjects were
      recruited in relation to a routine ultra-sound examination, and all pregnant
      women in Norway were eligible. We used data from the Medical Birth Registry of
      Norway and questionnaires both pre and post partum. Symptoms of anxiety and
      depression at six months postpartum were predicted in a linear regression
      analysis by WHO-categories of breastfeeding, symptoms of anxiety and depression
      prepartum (standardized score), and interaction terms between breastfeeding
      categories and prepartum symptoms of anxiety and depression. The results were
      adjusted for cesarean sections, primiparity, plural births, preterm births, and
      maternal smoking. RESULTS: First, prepartum levels of anxiety and depression were
      related to breastfeeding cessation (beta 0.24; 95% CI 0.21-0.28), and
      breastfeeding cessation was predictive of an increase in postpartum anxiety and
      depression ( beta 0.11; 95%CI 0.09-0.14). Second, prepartum anxiety and
      depression interacted with the relation between breastfeeding cessation and
      postpartum anxiety and depression ( beta 0.04; 95% CI 0.01-0.06). The
      associations could not be accounted for by the adjusting variables. CONCLUSIONS:
      Breastfeeding cessation is a risk factor for increased anxiety and depression.
      Women with high levels of anxiety and depression during pregnancy who stop
      breastfeeding early are at an additional multiplicative risk for postpartum
      anxiety and depression.

PMID- 22621669
TI  - CD44: a validated target for improved delivery of cancer therapeutics.
AB  - INTRODUCTION: Advances in cancer therapeutics, namely more effective and less
      toxic treatments, will occur with targeting strategies that enhance the tumor
      biodistribution and thwart normal tissue exposure of the drug. This review
      focuses on cancer drug targeting approaches that exploit the expression of the
      cell-surface proteoglycan family, CD44, on the tumor cell surface followed by
      some form of ligand binding and induced CD44 internalization and intracellular
      drug release: in effect using this as a 'Trojan Horse' to more selectively access
      tumor cells. AREAS COVERED: This review defines the origins of evidence for a
      linkage between CD44 expression and malignancy, and invokes contemporary views of
      the importance of putative CD44(+) cancer stem cells in disease resistance.
      Although the primary emphasis is on the most advanced and developed paths, those
      that have either made it to the clinic or are well-poised to get there, a wide
      scope of additional approaches at various preclinical stages is also briefly
      reviewed. EXPERT OPINION: The future should see development of drug targeting
      approaches that exploit CD44 expression on CSCs/TICs, including applications to
      cytotoxic agents currently in the clinic.

PMID- 22621670
TI  - Effect of low-level laser therapy (660 nm) on acute inflammation induced by
      tenotomy of Achilles tendon in rats.
AB  - In this study, we aimed to analyze the effects of low-level laser therapy (LLLT;
      660 nm) on levels of protein expression of inflammatory mediators after cutting
      Achilles tendon of rats. Thirty Wistar male rats underwent partial incisions of
      the left Achilles tendon, and were divided into three groups of 10 animals
      according to the time of euthanasia after injury: 6, 24 and 72 h. Each group was
      then divided into control group and LLLT group (treated with 100 mW, 3.57 W cm(
      2), 0.028 cm(2), 214 J cm(-2), 6 J, 60 s, single point). In LLLT group, animals
      were treated once time per day until the time of euthanasia established for each
      group. The group treated with LLLT showed a significant reduction of IL-1beta
      compared with control groups at three time points (6 h: P=0.0401; 24 h: P=0.0015;
      72 h: P=0.0463). The analysis of IL-6 showed significant reduction only in the
      LLLT group at 72 h compared with control group (P=0.0179), whereas IL-10 showed a
      significant increase in the treated group compared with control group at three
      experimental times (6 h: P=0.0007; 24 h: P=0.0256; 72 h: P<0.0001). We conclude
      that LLLT is an important modulator of inflammatory cytokines release after
      injury in Achilles tendon.

PMID- 22621671
TI  - The effects of levamisole on oxidative stress induced by copper intoxication in
      broilers.
AB  - AIM: To determine the effects of Cu and levamisole on concentrations of Cu and Fe
      in plasma and liver, and the effects of levamisole on lipid peroxidation induced
      by Cu intoxication in broiler chickens. METHODS: In a 2*4 factorial study, 80 one
      day-old Ross PM3 broiler chicks were fed diets for 21 days containing either 8
      mg/kg Cu (Low Cu) or 250 mg/kg Cu (High Cu) and were treated with 0 (L0), 4 (L4),
      8 (L8) or 16 (L16) mg/kg bodyweight levamisole per day from Day 7 of the study,
      on three consecutive days in their drinking water. This treatment was repeated
      three times, at 3-day intervals. On Day 21, blood samples were collected from
      each bird for analysis of concentrations of Cu, Fe and malondialdehyde, and
      activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT),
      superoxide dismutase, catalase and glutathione peroxidase (GSH-Px). The birds
      were killed and liver samples collected for analysis of Cu and Fe. RESULTS: Mean
      concentrations of Cu and Fe in plasma, and Cu in liver, were increased overall in
      the High Cu groups compared with the Low Cu groups (p<0.001). Compared with the
      L0 treatment group on the High Cu diet, treatments L4, L8 and L16 decreased
      concentrations of Cu in plasma, and L8 and L16 increased concentration of Cu in
      liver (p<0.05). Mean activities of AST and ALT were increased in untreated birds
      (L0) fed the High compared with Low Cu diets (p<0.01). In birds receiving the
      High Cu diet, treatments L4 and L8 decreased activities of AST, and L4 and L16
      decreased activity of ALT, compared with L0 (p<0.05). The High Cu diet induced an
      oxidative stress characterised by increased mean concentrations of
      malondialdehyde and decreased activities of superoxide dismutase, catalase and
      GSH-Px (p<0.001). Concentration of malondialdehyde, and activities of superoxide
      dismutase and catalase were not changed following levamisole treatment in birds
      on the High Cu diet, and activity of GSH-Px was decreased by the L4 and L8
      treatments compared with the L0 group. CONCLUSIONS AND CLINICAL RELEVANCE: The
      results of the study suggest that treatment with levamisole might alleviate the
      harmful effects of Cu on the liver, as demonstrated by decreased activities of
      AST and ALT induced by a diet containing 250 mg/kg Cu.

PMID- 22621673
TI  - Relationship between itch and psychological status of patients with atopic
      dermatitis.
AB  - BACKGROUND: Itching is a cardinal symptom of atopic dermatitis (AD). OBJECTIVE:
      The study aim was to evaluate the relationships between pruritus and stress,
      health-related quality of life (HRQoL) and depression in adult patients with AD.
      METHODS: Eight-nine patients (30 men and 59 women) with AD were included.
      Demographic and clinical data were collected. The intensity of pruritus was
      assessed according to the 10-point Visual Analogue Scale (VAS) and the 4-Item
      Itch Questionnaire, HRQoL according to Dermatology Life Quality Index, and
      depression symptoms with Beck's Depression Inventory (BDI). Stress experienced by
      patients was evaluated with Social Readjustment Rating Scale and Stress Self
      assessment Scale. RESULTS: The mean intensity of pruritus according to VAS was
      7.9 +/- 2.2 points, and according to 4-Item Itch Questionnaire 14.0 +/- 4.4
      points. The intensity of pruritus was related to the stress experienced by the
      patients prior to disease exacerbation (rho = 0.37, P < 0.001). A significant
      correlation between pruritus and HRQoL was also found (VAS: rho = 0.5, P < 0.001,
      4-Item Itch Questionnaire: rho = 0.5, P < 0.001) as well as between pruritus and
      BDI (VAS: rho = 0.44, P < 0.001, 4-Item Itch Questionnaire: rho = 0.51, P <
      0.001). Patients with symptoms suggesting depression had more intense pruritus
      compared with the rest of patients (VAS: 9.1 +/- 1.6 vs. 7.6 +/- 2.2 points, P =
      0.004; 4-Item Itch Questionnaire: 17.3 +/- 2.5 vs. 13.1 +/- 4.4 points, P <
      0.001). CONCLUSIONS: Itching intensity in AD plays an important role in
      determining patients' psychosocial well-being. Patients with atopic dermatitis
      require an effective, long-term antipruritic therapy to improve their QoL and
      reduce the potential risk of depression.

PMID- 22621672
TI  - Disruption of gallbladder smooth muscle function is an early feature in the
      development of cholesterol gallstone disease.
AB  - BACKGROUND; Decreased gallbladder smooth muscle (GBSM) contractility is a
      hallmark of cholesterol gallstone disease, but the interrelationship between
      lithogenicity, biliary stasis, and inflammation are poorly understood. We studied
      a mouse model of gallstone disease to evaluate the development of GBSM
      dysfunction relative to changes in bile composition and the onset of sterile
      cholecystitis. METHODS: BALB/cJ mice were fed a lithogenic diet for up to 8
      weeks, and tension generated by gallbladder muscle strips was measured. Smooth
      muscle Ca(2+) transients were imaged in intact gallbladder. KEY RESULTS: Lipid
      composition of bile was altered lithogenically as early as 1 week, with increased
      hydrophobicity and cholesterol saturation indexes; however, inflammation was not
      detectable until the fourth week. Agonist-induced contractility was reduced from
      weeks 2 through 8. GBSM normally exhibits rhythmic synchronized Ca(2+) flashes,
      and their frequency is increased by carbachol (3 MUm). After 1 week, lithogenic
      diet-fed mice exhibited disrupted Ca(2+) flash activity, manifesting as clustered
      flashes, asynchronous flashes, or prolonged quiescent periods. These changes
      could lead to a depletion of intracellular Ca(2+) stores, which are required for
      agonist-induced contraction, and diminished basal tone of the organ.
      Responsiveness of Ca(2+) transients to carbachol was reduced in mice on the
      lithogenic diet, particularly after 4-8 weeks, concomitant with appearance of
      mucosal inflammatory changes. CONCLUSIONS & INFERENCES: These observations
      demonstrate that GBSM dysfunction is an early event in the progression of
      cholesterol gallstone disease and that it precedes mucosal inflammation.

PMID- 22621674
TI  - Text summarization as a decision support aid.
AB  - BACKGROUND: PubMed data potentially can provide decision support information, but
      PubMed was not exclusively designed to be a point-of-care tool. Natural language
      processing applications that summarize PubMed citations hold promise for
      extracting decision support information. The objective of this study was to
      evaluate the efficiency of a text summarization application called Semantic
      MEDLINE, enhanced with a novel dynamic summarization method, in identifying
      decision support data. METHODS: We downloaded PubMed citations addressing the
      prevention and drug treatment of four disease topics. We then processed the
      citations with Semantic MEDLINE, enhanced with the dynamic summarization method.
      We also processed the citations with a conventional summarization method, as well
      as with a baseline procedure. We evaluated the results using clinician-vetted
      reference standards built from recommendations in a commercial decision support
      product, DynaMed. RESULTS: For the drug treatment data, Semantic MEDLINE enhanced
      with dynamic summarization achieved average recall and precision scores of 0.848
      and 0.377, while conventional summarization produced 0.583 average recall and
      0.712 average precision, and the baseline method yielded average recall and
      precision values of 0.252 and 0.277. For the prevention data, Semantic MEDLINE
      enhanced with dynamic summarization achieved average recall and precision scores
      of 0.655 and 0.329. The baseline technique resulted in recall and precision
      scores of 0.269 and 0.247. No conventional Semantic MEDLINE method accommodating
      summarization for prevention exists. CONCLUSION: Semantic MEDLINE with dynamic
      summarization outperformed conventional summarization in terms of recall, and
      outperformed the baseline method in both recall and precision. This new approach
      to text summarization demonstrates potential in identifying decision support data
      for multiple needs.

PMID- 22621675
TI  - Enhancer dysfunction: how the main regulators of gene expression contribute to
      cancer.
AB  - A genome-wide epigenetic analysis of enhancer elements in colon cancer has
      implicated distal gene regulatory DNA sequences in the establishment of an
      oncogenic transcriptional program.

PMID- 22621676
TI  - Implications of endotracheal tube biofilm in ventilator-associated pneumonia
      response: a state of concept.
AB  - INTRODUCTION: Biofilm in endotracheal tubes (ETT) of ventilated patients has been
      suggested to play a role in the development of ventilator-associated pneumonia
      (VAP). Our purpose was to analyze the formation of ETT biofilm and its
      implication in the response and relapse of VAP. METHODS: We performed a
      prospective, observational study in a medical intensive care unit. Patients
      mechanically ventilated for more than 24 hours were consecutively included. We
      obtained surveillance endotracheal aspirates (ETA) twice weekly and, at
      extubation, ETTs were processed for microbiological assessment and scanning
      electron microscopy. RESULTS: Eighty-seven percent of the patients were colonized
      based on ETA cultures. Biofilm was found in 95% of the ETTs. In 56% of the cases,
      the same microorganism grew in ETA and biofilm. In both samples the most frequent
      bacteria isolated were Acinetobacter baumannii and Pseudomonas aeruginosa.
      Nineteen percent of the patients developed VAP (N = 14), and etiology was
      predicted by ETA in 100% of the cases. Despite appropriate antibiotic treatment,
      bacteria involved in VAP were found in biofilm (50%). In this situation,
      microbial persistence and impaired response to treatment (treatment failure and
      relapse) were more frequent (100% vs 29%, P = 0.021; 57% vs 14%, P = 0.133).
      CONCLUSIONS: Airway bacterial colonization and biofilm formation on ETTs are
      early and frequent events in ventilated patients. There is microbiological
      continuity between airway colonization, biofilm formation and VAP development.
      Biofilm stands as a pathogenic mechanism for microbial persistence, and impaired
      response to treatment in VAP.

PMID- 22621677
TI  - Paediatrician's role in caring for children with learning difficulties.
AB  - AIM: Children with learning difficulties are commonly seen in Australian
      paediatric outpatient settings. The practice patterns of paediatricians in
      assessing, referring and managing these children are unknown, and there is no
      consensus on best practice. We thus aimed to examine the consistency between
      Australian paediatricians': (i) assessment; (ii) referral; and (iii) management
      of children presenting with learning difficulties. METHODS: All 373 paediatrician
      members of the Australian Paediatric Research Network were invited to participate
      in an online survey in 2010. Paediatricians who saw children with learning
      difficulties were asked questions about their assessment, referral and management
      practices. RESULTS: Of 181 (49%) paediatricians to complete the survey, 140 (77%)
      reported seeing patients with learning difficulties. Most often, paediatricians
      supplemented their clinical assessments with audiology assessments (75%), teacher
      or parent questionnaires (60-65%), or teacher contact (51%). Paediatricians used
      medical investigations (40%), direct assessment tools (27%) or a school visit
      (4%) less often. Most paediatricians referred children with learning difficulties
      to educational psychology (84%), special education (61%) or speech therapy (66%)
      services but less often to occupational therapy (34%) or mental health (15%)
      services. The most common management strategies were to provide a report to the
      school (76%) or parents (66%) and to make recommendations around sleep hygiene
      (75%) and for tutoring (66%). CONCLUSIONS: Australian paediatric practice in this
      area is diverse, with the greatest variability around management practices. These
      data provide a case for designing and implementing evidence-based guidelines for
      the paediatric care of children who struggle to learn in school.

PMID- 22621678
TI  - Globalisation and global health governance: implications for public health.
AB  - Globalisation is a defining economic and social trend of the past several
      decades. Globalisation affects health directly and indirectly and creates
      economic and health disparities within and across countries. The political
      response to address these disparities, exemplified by the Millennium Development
      Goals, has put pressure on the global community to redress massive inequities in
      health and other determinants of human capability across countries. This, in
      turn, has accelerated a transformation in the architecture of global health
      governance. The entrance of new actors, such as private foundations and multi
      stakeholder initiatives, contributed to a doubling of funds for global health
      between 2000 and 2010. Today the governance of public health is in flux, with
      diminished leadership from multilateral institutions, such as the WHO, and poor
      coherence in policy and programming that undermines the potential for sustainable
      health gains. These trends pose new challenges and opportunities for global
      public health, which is centrally concerned with identifying and addressing
      threats to the health of vulnerable populations worldwide.

PMID- 22621679
TI  - Impact of peri-transplant heart failure & left-ventricular diastolic dysfunction
      on outcomes following liver transplantation.
AB  - BACKGROUND & AIMS: Assess the prevalence of peri-transplant heart failure and its
      potential relation to post-transplant morbidity and mortality. METHODS: A
      retrospective study was performed on 234 consecutive cirrhotic patients
      undergoing liver transplantation in a single European center from 1999 to 2007
      (mean age 52, 30% women, 36% with alcoholic liver disease, 24% with viral
      hepatitis, 18% cholestatic liver disease). Left ventricular diastolic dysfunction
      was defined as E/A ratio <= 1. We used the Boston classification for heart
      failure to assess the prevalence of peri-transplant heart failure. Patients were
      followed up for a mean of 4 years post-transplant (0.5-9 years). RESULTS:
      Eighteen per cent of patients demonstrated diastolic dysfunction pretransplant.
      During the peri-transplantation period highly possible heart failure occurred in
      27%. In logistic regression analysis, heart failure was independently related to
      lower mean arterial blood pressure (OR 0.94, 95% CR 0.91-0.98) and prolonged
      corrected QT time on ECG (OR 9.10, 95% CI 3.77-21.93) pretransplant. Peri
      transplant mortality amounted to 5%, and was independently related to heart
      failure (OR 15.11, 95% CI 1.76-129.62) and the peri-transplant need of dialysis
      (OR 14.18, 95% CI 1.65-121.89). Heart failure was also associated with longer
      stay in the intensive care unit and peri-transplant cardiac events (P < 0.05).
      Long-term transplant-free mortality was independently related to diastolic
      dysfunction at baseline (Hazard ratio 4.82, 95% CI 1.78-13.06). CONCLUSION: Heart
      failure occurs in approximately a quarter of patients with cirrhosis following
      liver transplantation and it is an independent predictor of mortality and
      morbidity.

PMID- 22621680
TI  - Paraoxonase lactonase activity (PON-HTLase), asymmetric dimethylarginine (ADMA)
      and platelet activating factor-acetylhydrolase (PAF-AH) activity in non-obese
      women with PCOS.
AB  - OBJECTIVE: Paraoxonase1 (PON1), exhibits both esterase activity (PON1-AREase) and
      homocysteine thiolactonase activity (PON1-HTLase) which respectively prevent LDL
      oxidation and detoxify homocysteine thiolactone (HTL). Platelet-activating factor
      acetylhydrolase (PAF-AH) is an antioxidant enzyme preventing LDL oxidation by
      hydrolysis of oxidized phospholipids. Both of these enzymes exhibit a
      proatherogenic role. ADMA is an endogenous inhibitor of nitric oxide (NO)
      synthesis causing endothelial dysfunction. The aim was to compare non-obese PCOS
      patients with a BMI matched control group using the following characteristics:
      serum PON1-HTLase, ADMA, PAF-AH, and lipid and hormonal parameters. RESULTS: 77
      women with PCOS and 25 healthy subject were recruited for this study, The
      controls were non-obese BMI and age matched with the patients. There were no
      significant differences with respect to age, BMI, FSH, free testosterone, DHEA,
      androstenadion, total cholesterol, triglycerides, HDL, LDL, VLDL, fasting
      glucose/insulin ratio and HOMA-IR among the groups (p > 0.05). However, total
      testosterone and fasting glucose levels were significantly higher in the PCOS
      group (p < 0.05). On the other hand, PON1-HTLase levels (39.6 +/- 5.77 vs. 33.8
      +/- 8.2, p = 0.02) were significantly lower in the PCOS group while ADMA levels
      (1.14 +/- 0.6 vs. 3.37 +/- 6.4, p = 0.004) were significantly higher in the PCOS
      group. However, there was no significant difference in PAF-AH activity among the
      groups. CONCLUSIONS: Decreased PON1-HTLase and increased ADMA levels might be a
      relevant marker for the development of future atherosclerotic heart disease (AHD)
      in non-obese PCOS patients. Further studies are needed to confirm our results.

PMID- 22621681
TI  - Improving the quality of emergency medicine care by developing a quality
      requirement framework: a study from The Netherlands.
AB  - BACKGROUND: In The Netherlands, mainly inexperienced physicians work in the ED on
      all shifts, including the evening and night shifts, when no direct supervision is
      available. In 2004 a report of the Dutch Health Care Inspectorate revealed that
      quality of care at Emergency Departments (EDs) was highly variable. Based on this
      report and international studies showing significant potential for quality
      improvement, stakeholders felt the need to improve the quality of EM care. Based
      on the literature, a baseline measurement and a panel of experts, The Netherlands
      recently developed a nationwide quality requirement framework (QRF) for EM. This
      article describes the content of and path to this QRF. METHODS: To conduct a
      baseline measurement, the panel needed to identify measurable entities related to
      EM care at EDs. This was done by formulating both qualitative and partly
      quantitative questions related to the following competence areas: triage system,
      training of personnel (physicians and nurses), facilities and supervision of
      physicians.27 out of 104 Dutch EDs were sampled via a cross-sectional study
      design, using an online survey and standardized follow-up interview in which the
      answers of the survey were reviewed. RESULTS: In the QRF, EM care is divided into
      a basic level of EM care and six competence certification areas (CCAs): (acute)
      abdominal aortic aneurysm, acute coronary syndrome, acute psychiatric behavioral
      disorder, cerebral vascular accident, pediatric critical care and infants with
      low birth weight. For the basic level of EM care and for every CCA minimum
      prerequisites for medical devices and training of personnel are established. The
      factors selected for the QRF can be regarded as minimum quality standards for EM
      care. A major finding of this study was that in The Netherlands, none of the 27
      sampled EDs demonstrated compliance with these factors. CONCLUSION: Our study
      shows that Dutch EDs fall short of what the expert consensus panelists considered
      minimum prerequisites for adequate EM care. The process of systematic enquiry
      allowed this information to come to light for the first time, which resulted in
      the implementation of a QRF for Dutch ED personnel, that is intended improve
      quality of EM care over time. This is an important development for the worldwide
      EM community as the QRF shows a way to generate interim standards to improve the
      chances of appropriate delivery of EM care when the gold standard of providing
      fully qualified EPs is not initially achievable.

PMID- 22621683
TI  - Characterizing agosticity using the quantum theory of atoms in molecules: bond
      critical points and their local properties.
AB  - In this paper, we extend the work of Popelier and Logothetis [J. Organomet. Chem.
      1998, 555, 101] on the characterization of agosticity by considerably enlarging
      the set of the studied organometallic molecules. To this aim, 23 representative
      complexes have been considered, including all first line transition metals at
      various oxidation states and exhibiting four types of agosticity (alpha, beta,
      gamma, and delta). From these examples, the concepts of agostic atom, agostic
      bond, and agostic interaction are defined and discussed, notably by advocating
      Bader's analysis of the electron density. The nature and the local properties of
      the bond critical points are then investigated, and the relationships with the
      main geometric parameters of the complexes are particularly examined. Moreover,
      new local descriptors based on kinetic energy densities are developed in order to
      provide new tools for bond characterization.

PMID- 22621682
TI  - "It's a hidden issue": exploring the experiences of women with HIV-associated
      neurocognitive challenges using a disability framework.
AB  - PURPOSE: To use the World Health Organization's International Classification of
      Functioning, Disability and Health (ICF) to explore the experiences of women
      living with self-identified HIV-associated neurocognitive challenges. METHOD:
      This interpretive, qualitative study involved key informant interviews with 16
      women with self-identified HIV-associated neurocognitive challenges. Data were
      collected through 60-90 min, in-depth, semi-structured interviews. Thematic
      analysis was performed using an inductive approach. Theoretical analysis then
      used the ICF to reconceptualize the data using a disability lens. RESULTS:
      Participants perceived impairments (e.g. memory loss, difficulty multi-tasking)
      and participation restrictions (e.g. parenting, work roles) resulting from their
      neurocognitive challenges as having a larger impact on their daily lives than
      activity limitations (e.g. difficulty with chores). Participants held contrasting
      views about parenting: women with children drew strength from parenting whereas
      women without children worried that parenting could compromise their health.
      Participation in work and volunteering roles was viewed as integral to managing
      neurocognitive challenges and health overall. CONCLUSIONS: Conceptualizing
      neurocognitive challenges through a disability lens focuses attention on how
      impairments interact with other realities in these women's lives. This
      exploratory study reveals the need for future research exploring perceptions
      among people living with HIV-associated neurocognitive challenges with attention
      to aging and among other vulnerable groups.

PMID- 22621684
TI  - Replacing ranibizumab with bevacizumab on the Pharmaceutical Benefits Scheme:
      where does the current evidence leave us?
AB  - The battle between two anti-vascular endothelial growth factor (VEGF) treatment
      options (ranibizumab and bevacizumab) for neovascular macular degeneration is a
      topic of particular significance to eye health professionals with an interest in
      cost-effective treatment. Being the first of its kind directly comparing the two
      anti-VEGF, a recent large multicentre clinical trial has shown that bevacizumab
      is not inferior when compared with ranibizumab in regards to efficacy of visual
      acuity outcomes; the evidence at this stage is inconclusive for safety outcomes.
      Before bevacizumab can be considered a justifiable replacement for the much more
      expensive ranibizumab on the Pharmaceutical Benefits Scheme (PBS), its safety in
      treatment needs further supporting evidence.

PMID- 22621685
TI  - Identification of active sequences in the L4a domain of laminin alpha5 promoting
      neurite elongation.
AB  - Laminin alpha5 is an extracellular matrix protein containing multiple domains
      implicated in various biological processes, such as embryogenesis and renal
      function. In this study, we used recombinant proteins and synthetic peptides to
      identify amino acid residues within the short arm region of alpha5 that were
      critical for neurite outgrowth activity. The short arm of alpha5 contains three
      globular domains (LN, L4a, and L4b) and three rodlike elements (LEa, LEb, and
      LEc). Recombinant proteins comprised of the alpha5 short arm fused with a Fc tag
      produced in 293 cells were assayed for PC12 (pheochromocytoma) cell adhesion and
      neurite outgrowth activities. Although it did not have cell attachment activity,
      neurite outgrowth was promoted by the recombinant protein. To narrow the region
      involved in neurite outgrowth activity, two truncated recombinant proteins were
      produced in 293 cells. A recombinant protein lacking L4a and LEb lost activity.
      Furthermore, we synthesized 78 partially overlapping peptides representing most
      of the amino acid sequences of L4a and LEb. Of the peptides, A5-76 [mouse laminin
      alpha5 928-939 (TSPDLFRLVFRY) in L4a] exhibited neurite outgrowth activity.
      Mutagenesis studies showed that Phe(933) and Arg(934) were involved in neurite
      outgrowth activity. Moreover, inhibition assays using anti-integrin monoclonal
      antibodies showed that neurite outgrowth on the alpha5 short arm was partially
      mediated by integrin alpha1beta1. However, the antibodies to integrin alpha1 and
      beta1 did not inhibit neurite elongation on the A5-76 peptide. These results
      suggest that in addition to cellular interactions with the active site in the L4a
      domain, the binding of integrin alpha1beta1 seems to modulate neurite elongation
      on the short arm of alpha5.

PMID- 22621686
TI  - Protein arginine methyltransferases (PRMTs) as therapeutic targets.
AB  - INTRODUCTION: Protein arginine methyltransferases (PRMTs) add one or two
      monomethyl groups to the guanidino nitrogen atoms of arginine residues, resulting
      in epigenetic modification of histones or changes of protein-protein
      interactions, which in turn leads to the regulation of a variety of biological
      functions, including transcriptional activation/repression, signal transduction,
      cell differentiation, and embryonic development. As dysregulation of PRMTs has
      been observed in diverse types of cancers and modulation of their levels affects
      cancer cell growth, these enzymes are considered to be potential therapeutic
      targets. AREAS COVERED: In this review, we examined recent advances in our
      understanding of the regulatory mechanisms of PRMT activity and the biological
      roles of PRMTs in embryonic stem cell, Wnt/beta-catenin signaling, and cancer
      development. EXPERT OPINION: The roles of PRMTs have been fairly well
      established, but further studies are required to determine how PRMTs are
      regulated by cellular signaling pathways in vivo. Since the usage of adult stem
      cells is under intense scrutiny by society, identification of the roles of PRMTs
      in adult stem cells is expected in the near future. Although small molecules
      specific to PRMTs with high potency in vitro have been identified, development of
      small molecules that can regulate the activity of PRMTs in vivo is urgently
      required for therapeutic purposes.

PMID- 22621687
TI  - Heterozygote genotypes at rs2222823 and rs2811712 SNP loci are associated with
      cerebral small vessel disease in Han Chinese population.
AB  - AIMS: With developments of etiology of cerebral small vessel disease (CSVD) and
      genome-wide association study (GWAS) of stroke, the genetic studies of CSVD are
      focused on genes related to blood-brain barrier (BBB) and aging. The project aims
      to investigate the association between CSVD and susceptibility loci and candidate
      genes. METHODS: All study subjects admitted Beijing Tiantan Hospital from June
      2009 to September 2010 including 197 cerebral small vessel disease patients(S),
      198 large artery atherosclerosis control individuals (vascular stenotic rate
      >=50% diameter reduction) (L), 200 hypertensive intracerebral hemorrhage control
      individuals (H) and 197 stroke-free control individuals (C). 15 SNPs in 4 genes
      (MYLK, AQP4, NINJ2, and INK4/ARF) were genotyped using Multiplex Snapshot assay.
      Each SNP was first examined between the groups S and C in different genetic
      models (codominant, dominant, recessive, overdominant, and log-additive).
      Permutation correction was used to adjust for multiple testing. The significant
      SNP loci were further analyzed in comparing S with L and H, respectively.
      Subgroup analysis was also performed for each risk-factor category. RESULTS:
      Among the 15 SNPs, rs2222823 and rs2811712 were found to be significantly
      associated with CSVD after multiple-testing adjustment. The heterozygote (A/T) of
      rs2222823 of MYLK has an odds ratio of 0.52 (95% CI =[0.35, 0.79], P= 0.002,
      adjusted P= 0.031) when compared with homozygotes. The heterozygote (C/T) of
      rs2811712 of INK4/ARF has an odds ratio of 1.75 (95% CI =[1.13-2.71], P= 0.004,
      adjusted P= 0.050). The SNP rs2222823 was significant (P= 0.035) in comparing S
      with H. In comparing S versus L, it is significant for the subgroups of patients
      without diabetes (P= 0.012) and drinking (P= 0.018). rs2811712 was significant in
      comparing S with L for the subgroups of patients with hyperlipidemia (P= 0.029)
      and drinking (P= 0.04). CONCLUSION: The heterozygotes (T/A) at the rs2222823 SNP
      locus of MYLK gene decreases the risk of having cerebral small vessel disease,
      while the heterozygotes (C/T) at the rs2811712 SNP locus of INK4/ARF gene
      increases the risk, suggesting that the MYLK and INK4/ARF are the associated
      genes of cerebral small vessel disease in Han Chinese population.

PMID- 22621688
TI  - Histopathological examination of chronic laminitis in Kaimanawa feral horses of
      New Zealand.
AB  - AIMS: To investigate the prevalence, histopathological and histomorphometric
      presentation of chronic laminitis in a population of Kaimanawa feral horses.
      METHODS: Following the capture and euthanasia of feral horses from the Kaimanawa
      Ranges of New Zealand, the left forefoot of 28 stallions and 28 mares aged
      between 6 and 12 years were removed and processed for histology. Sections of
      lamellar samples from each horse were examined using light microscopy. The
      presence of laminitis was assessed and the histopathological lesions were
      described. Horses were grouped by histological diagnosis into laminitic and non
      laminitic groups and histomorphometric analysis was conducted and compared
      between groups. The parameters examined were total length of primary epidermal
      lamellae (PEL), keratinised length of PEL, and the length of secondary epidermal
      lamellae (SEL) at the abaxial end and axial end of each PEL. RESULTS: Of the
      horses examined, 25 (45%) were diagnosed with chronic laminitis. The most
      prevalent histopathological features were the presence of excessive cap horn, and
      multi-branched and attenuated SEL. Histomorphometric assessment of the lamellar
      architecture revealed no difference in morphometric measurements between the
      normal and laminitic groups for any parameter measured (p>0.05). CONCLUSIONS: The
      current study found a high prevalence of laminitis in feral Kaimanawa horses. The
      reason for this in the Kaimanawa population is not known. Histomorphometric
      analysis may not be a good indicator of chronic laminitis in feral horses.
      CLINICAL RELEVANCE: It is an important finding that the feral horse lifestyle in
      the environment of the Kaimanawa Ranges in New Zealand offers no protection
      against foot disease. The finding suggests that horses are vulnerable to
      laminitis whether in domestic care or in a feral habitat.

PMID- 22621689
TI  - Dual inhibitors for aspartic proteases HIV-1 PR and renin: advancements in AIDS
      hypertension-diabetes linkage via molecular dynamics, inhibition assays, and
      binding free energy calculations.
AB  - Human immunodeficiency virus type 1 protease (HIV-1 PR) and renin are primary
      targets toward AIDS and hypertension therapies, respectively. Molecular mechanics
      Poisson-Boltzmann surface area (MM-PBSA) free-energy calculations and inhibition
      assays for canagliflozin, an antidiabetic agent verified its effective binding to
      both proteins (DeltaG(pred) = -9.1 kcal mol(-1) for canagliflozin-renin;
      K(i,exp)= 628 nM for canagliflozin-HIV-1 PR). Moreover, drugs aliskiren (a renin
      inhibitor) and darunavir (an HIV-1 PR inhibitor) showed high affinity for HIV-1
      PR (K(i,exp)= 76.5 nM) and renin (K(i,pred)= 261 nM), respectively. Importantly,
      a high correlation was observed between experimental and predicted binding
      energies (r(2) = 0.92). This study suggests that canagliflozin, aliskiren, and
      darunavir may induce profound effects toward dual HIV-1 PR and renin inhibition.
      Since patients on highly active antiretroviral therapy (HAART) have a high risk
      of developing hypertension and diabetes, aliskiren-based or canagliflozin-based
      drug design against HIV-1 PR may eliminate these side-effects and also facilitate
      AIDS therapy.

PMID- 22621690
TI  - Assessing accuracy of an electronic provincial medication repository.
AB  - BACKGROUND: Jurisdictional drug information systems are being implemented in many
      regions around the world. British Columbia, Canada has had a provincial
      medication dispensing record, PharmaNet, system since 1995. Little is known about
      how accurately PharmaNet reflects actual medication usage. METHODS: This
      prospective, multi-centre study compared pharmacist collected Best Possible
      Medication Histories (BPMH) to PharmaNet profiles to assess accuracy of the
      PharmaNet profiles for patients receiving a BPMH as part of clinical care. A
      review panel examined the anonymized BPMHs and discrepancies to estimate clinical
      significance of discrepancies. RESULTS: 16% of medication profiles were accurate,
      with 48% of the discrepant profiles considered potentially clinically significant
      by the clinical review panel. Cardiac medications tended to be more accurate
      (e.g. ramipril was accurate >90% of the time), while insulin, warfarin,
      salbutamol and pain relief medications were often inaccurate (80-85% of the
      time). 1215 sequential BPMHs were collected and reviewed for this study.
      CONCLUSIONS: The PharmaNet medication repository has a low accuracy and should be
      used in conjunction with other sources for medication histories for clinical or
      research purposes. This finding is consistent with other, smaller medication
      repository accuracy studies in other jurisdictions. Our study highlights specific
      medications that tend to be lower in accuracy.

PMID- 22621691
TI  - Management of metastatic castration-resistant prostate cancer: recent advances.
AB  - Metastatic prostate cancer remains a considerable therapeutic challenge; however,
      advances in clinical research have resulted in five new treatments in the last 2
      years. The immunotherapy sipuleucel-T, the cytotoxic cabazitaxel, the androgen
      biosynthesis inhibitor abiraterone acetate, the radioisotope alpharadin and the
      anti-androgen MDV3100 have all been shown to improve overall survival in
      randomized phase III studies for patients with metastatic castration-resistant
      prostate cancer. The therapeutic strategies of targeting androgen-receptor
      signalling and other key intracellular pathways involved in tumour progression
      and treatment resistance are yielding promising results. Agents such as the dual
      vascular endothelial growth factor receptor/MET inhibitor cabozantinib, the
      clusterin inhibitor custirsen and the Src inhibitor dasatinib have shown
      encouraging results in phase II studies. Novel immunotherapeutics such as
      prostate-specific membrane antigen-directed therapy and the anti-cytotoxic T
      lymphocyte-associated receptor 4 (CTLA4) antibody ipilimumab are also under
      investigation. Optimal methods of treatment selection, combination and sequencing
      have yet to be determined.

PMID- 22621692
TI  - Epidemiology and management of Kawasaki disease.
AB  - Kawasaki disease (KD) is an acute systemic vasculitis affecting young children
      and is rising in incidence worldwide. It is most common in children <5 years of
      age, males and those of Asian ethnicity. It is an important cause of acquired
      heart disease in children. Standard treatment with high-dose aspirin
      (acetylsalicylic acid; ASA) and intravenous immune globulin (IVIG) has been shown
      to decrease the rate of coronary artery aneurysm development. Anti-coagulation
      has an important place in the management of KD, although guidance based on
      evidence is lacking. Treatment of refractory KD is an area under intense study
      and may include IVIG, corticosteroids and/or tumour necrosis factor (TNF)-alpha
      inhibitors among immunosuppressive agents. Acute complications of KD include
      myocarditis/KD shock syndrome and macrophage activation syndrome, which
      necessitate appropriate awareness in order to initiate proper management.

PMID- 22621695
TI  - Immune globulin subcutaneous (human) 20%: in primary immunodeficiency disorders.
AB  - Immune globulin subcutaneous 20% is a new high-concentration (200 g/L) solution
      of highly purified human IgG (>=98%) indicated in the EU and the US for antibody
      replacement therapy in patients with primary immunodeficiency with antibody
      deficiency, and in the EU for replacement therapy in humoral immunodeficiency
      secondary to myeloma or chronic lymphocytic leukaemia. Immune globulin
      subcutaneous 20% is formulated with L-proline, which imparts long-term stability
      at room temperature and a relatively low viscosity. In two pivotal phase III
      trials in stably treated patients with primary immunodeficiency, immune globulin
      subcutaneous 20% at weekly subcutaneous dosages either equivalent to each
      patient's previous intravenous or subcutaneous replacement therapy, or providing
      equivalent systemic exposure to previous intravenous therapy, produced mean serum
      IgG trough levels equal to or greater than pre-study levels. In each trial, there
      were no serious bacterial infections during treatment throughout the 28-week or
      12-month efficacy periods. The rates of infectious episodes, days missed from
      work/school, days hospitalized or days with antibiotics were low. Immune globulin
      subcutaneous 20% was generally well tolerated. A high proportion of patients
      experienced local infusion-site reactions, but infusion-related systemic adverse
      events were relatively infrequent. Most adverse events were of mild or moderate
      intensity and did not interfere with therapy.

PMID- 22621693
TI  - Treatment of pulmonary arterial hypertension in connective tissue disease.
AB  - Pulmonary arterial hypertension (PAH) is a group of distinct disorders that
      includes idiopathic PAH (IPAH), familial PAH and PAH associated with other
      conditions (APAH) such as connective tissue disease (CTD-APAH) or congenital
      heart disease. PAH is characterized by increased pulmonary arterial pressure and
      pulmonary vascular resistance. If left untreated, PAH can lead to right heart
      failure and premature death. CTD-APAH represents an important clinical subgroup
      of APAH that has a higher risk of death than IPAH. The European treatment
      guidelines advocate the use of PAH-targeted therapies including bosentan,
      ambrisentan, sildenafil, inhaled iloprost, intravenous epoprostenol (I-A
      recommendations), tadalafil or treprostinil (I-B recommendations) for patients in
      WHO functional class II-III. Not all randomized clinical studies of the approved
      PAH-targeted therapies have included patients with CTD-APAH. The purpose of this
      review is to describe the clinical characteristics of CTD-APAH and discuss the
      approved pharmacological treatments, with a focus on data specific to this
      subgroup where possible.

PMID- 22621696
TI  - Intravenous ibuprofen: in adults for pain and fever.
AB  - Ibuprofen is a well established analgesic, anti-inflammatory and antipyretic
      NSAID. In three double-blind, multicentre trials in postoperative adult patients
      (n = 185-406), intravenous ibuprofen 800 mg once every 6 hours, as an adjunct to
      morphine, significantly reduced the consumption of morphine compared with
      placebo, as an adjunct to morphine, in two of the three trials (primary endpoint
      in two trials); the between-group difference attained statistical significance in
      the third trial utilizing a Log-rank transformed analysis. Adjunctive ibuprofen
      therapy also provided significantly better pain relief during movement than
      adjunctive placebo for the period from 6 to 24 or 28 hours after the first dose
      (primary endpoint in one trial). Furthermore, intravenous ibuprofen plus morphine
      generally provided better pain relief than placebo plus morphine at all time
      periods evaluated throughout the first 24 or 28 hours, irrespective of whether
      this was assessed during rest or movement. In three double-blind, single- or
      multicentre trials (n = 60-120) in febrile hospitalized adult patients with acute
      malaria or with varying causes of fever, intravenous ibuprofen (100-400 mg every
      4 or 6 hours, or 800 mg every 6 hours) reduced fever to a significantly greater
      extent than placebo (primary endpoint in two trials) and/or significantly more
      patients achieved a temperature of <38.3 degrees C within 4 hours of the first
      ibuprofen 400 mg dose than with placebo (primary endpoint in the third trial).
      Intravenous ibuprofen was generally well tolerated by hospitalized adult patients
      participating in these clinical trials. The most common adverse event leading to
      discontinuation of ibuprofen treatment was pruritus (<1% of patients).

PMID- 22621694
TI  - The role of capecitabine in locally advanced rectal cancer treatment: an update.
AB  - Preoperative infusional 5-fluorouracil (5-FU) and concurrent radiation therapy
      (RT) followed by total mesorectal surgery is the current standard of care for
      locally advanced rectal cancer (LAR). When compared with postoperative 5-FU-based
      chemoradiation, this strategy is associated with significantly lower rates of
      local relapse, lower toxicity and better compliance. Capecitabine is a rationally
      designed oral prodrug that is converted into 5-FU by intracellular thymidine
      phosphorylase. Substitution of infusional 5-FU with capecitabine is an attractive
      option that provides a more convenient administration schedule and, possibly,
      increased efficacy. Indeed, incorporation of capecitabine in combined modality
      neoadjuvant therapy for LAR has been under intense investigation during the last
      10 years. Phase I and II clinical trials showed that a regimen consisting of
      capecitabine 825mg/m(2) twice daily for 7 days/week continuous oral
      administration in combination with RT is an active and well tolerated regimen,
      thereby being the preferred concurrent regimen. The definitive demonstration that
      efficacy of capecitabine/RT is similar to 5-FU/RT has been provided by the NSABP
      R-04 and the German Margit trials. One approach to improve outcomes in rectal
      cancer is to deliver a second RT-sensitizing drug with effective systemic
      activity. Oxaliplatin and irinotecan are therefore good candidates. However, two
      phase III trials demonstrated that incorporation of oxaliplatin to capecitabine
      with RT did not improve early outcomes and, by contrast, increased toxicity.
      Capecitabine has also been combined with irinotecan. This regimen showed
      encouraging results in phase I and II clinical trials, which led to an ongoing
      phase III clinical trial. New strategies with induction chemotherapy with or
      without chemoradiation prior to surgery are currently under investigation.
      Whether or not capecitabine has a role in this setting is being investigated in
      ongoing trials. Incorporation of agents directed towards new targets, such as
      anti-epidermal growth factor receptor (EGFR) antibodies or antiangiogenic agents,
      in combination preoperative regimens, is being hampered by results of early
      trials in which efficacy outcomes with cetuximab were poor and an excessive rate
      of surgical complications with bevacizumab was observed. The lack of improvements
      in efficacy with the addition of cetuximab or bevacizumab in the adjuvant
      treatment of colon cancer led to concerns about further development of these
      agents in rectal cancer. The role of capecitabine in the postoperative adjuvant
      setting is the aim of the ongoing Dutch SCRIPT trial. The prediction of response
      associated with capecitabine has been based on expression of thymidylate synthase
      and dihydropyrimidine dehydrogenase, as well as on gene expression arrays. All
      these procedures require further validation and should be considered as
      investigational. In conclusion, capecitabine can safely and effectively replace
      intravenous continuous infusion of 5-FU in the preoperative chemoradiation
      setting for rectal cancer management. The addition of other new antineoplastic
      agents to a fluoropyrimidine-based regimen remains investigational.

PMID- 22621697
TI  - MicroRNAs in the pathogenesis of malignant melanoma.
AB  - Cutaneous malignant melanoma is the most aggressive and lethal form of skin
      cancer. Over the past decades, its incidence has been increasing by 3-8% per year
      in western countries while mortality has stabilized. Melanoma is a heterogenous
      disease and can be subclassified based on distinct clinical characteristics,
      histopathological features and mutation patterns within NRAS and BRAF genes.
      Recent data indicate that microRNAs (miRNAs) are involved in the pathogenesis of
      malignant melanoma. MiRNAs are small, non-coding, regulatory RNA molecules
      expressed in a tissue and cell specific manner and are known to play a crucial
      role in cell homeostasis and carcinogenesis. MiRNAs might prove to be powerful
      cancer biomarkers and future therapeutic targets. In this review, we focused on
      the miRNA involvement in four molecular pathways known to be deregulated in
      malignant melanoma, including the RAS-RAF-MEK-ERK pathway, the p16(INK4A) -CDK4
      RB pathway, the PIK3-AKT pathway and the MITF pathway.

PMID- 22621698
TI  - Layer cake: the first bite at gene expression diversity in the human brain.
AB  - A recent publication has provided a comprehensive atlas of gene expression
      profiles of 995 genes linked to neuronal functions in two regions of the human
      brain neocortex.

PMID- 22621700
TI  - Photoionization of oxidized coenzyme Q in microemulsion: laser flash photolysis
      study in biomembrane-like system.
AB  - Photoexcitation to generate triplet state has been proved to be the main
      photoreaction in homogeneous system for many benzoquinone derivatives, including
      oxidized coenzyme Q (CoQ) and its analogs. In the present study, microemulsion of
      CoQ, a heterogeneous system, is employed to mimic the distribution of CoQ in
      biomembrane. The photochemistry of CoQ(10)  in microemulsion and cyclohexane is
      investigated and compared using laser flash photolysis and results show that
      CoQ(10)  undergoes photoionization via a monophotonic process to generate radical
      cation of CoQ(10)  in microemulsion and photoexcitation to generate excited
      triplet state in cyclohexane. Meanwhile, photoreactions of duroquinone (DQ) and
      CoQ(0)  in microemulsion are also investigated to analyze the influence of
      molecular structure on the photochemistry of benzoquinone derivatives in
      microemulsion. Results suggest that photoexcitation, which is followed by excited
      state-involved hydrogen-abstraction reaction, is the main photoreaction for DQ
      and CoQ(0)  in microemulsion. However, photoexcited CoQ(0)  also leads to the
      formation of hydrated electrons. The isoprenoid side chain-involved high
      resonance stabilization is proposed to explain the difference in photoreactions
      of CoQ(0)  and CoQ(10)  in microemulsion. Considering that microemulsion is close
      to biomembrane system, its photoionization in microemulsion may be helpful to
      understand the real photochemistry of biological quinones in biomembrane system.

PMID- 22621701
TI  - Including gynecological teaching associates' perspectives in women's health
      exams: lessons for improved communication practices.

PMID- 22621702
TI  - F8 gene dosage defects in atypical patients with severe haemophilia A.
AB  - We performed molecular analysis of the factor 8 gene (F8) in 272 unrelated
      Spanish patients with haemophilia A (HA) and detected a mutation by routine
      analysis in 267 of them (98.1%). No mutation was detected in the remaining five
      patients despite clinical and laboratory confirmation of HA. The aim is to
      describe the molecular alterations in F8 discovered by gene dosage methodologies
      in three of these patients. For methodology, F8 sequencing, intragenic marker
      analysis, multiplex ligation-dependent probe amplification and quantitative real
      time-PCR were followed. One patient had Klinefelter syndrome (47,XXY) and a large
      deletion spanning exons 1-12 masked by the other F8 allele; the second patient
      showed a large duplication spanning exons 2-10 and the third patient revealed a
      non-contiguous double duplication of exons 14 and 23-25. The remaining two
      patients had mild HA and dosage results were normal. The application of gene
      dosage methods is useful to define haemophilic patients in whom mutations are not
      detected using other routine methods. Nevertheless, in a small percentage of
      patients (<1%), no molecular pathology can be identified after testing several
      genetic methodologies.

PMID- 22621704
TI  - Cloning of the lanosterol 14-alpha-demethylase ( ERG11 ) gene in  Trichosporon
      asahii: a possible association between G453R amino acid substitution and azole
      resistance in  T. asahii.
AB  - Lanosterol 14-alpha-demethylase ( Erg11 protein; Erg11p ), encoded by the ERG11
      gene, is the primary target of azoles. Recently, a change in affinity of this
      enzyme for azoles has been reported as a resistance mechanism in several fungal
      species. Trichosporon asahii ( T. asahii) is susceptible to fluconazole (FLC).
      This report identified the ERG11 gene of T. asahii (NCBI accession; HQ176415).
      The Erg11p of T. asahii, presumed from the DNA sequence, was closely related to
      the Erg11p of Cryptococcus neoformans. Furthermore, a FLC-susceptible strain was
      cultured in medium containing FLC at concentrations from 4.0 to 16 MUg mL(-1)  in
      order to analyze the development of FLC resistance in T. asahii. The degree of
      resistance was related to the FLC concentration of the growth medium. One highly
      resistant strain that was cultured in the medium containing 16 MUg mL(-1)  FLC
      contained 1 point mutation (G1357C) that caused a single amino acid substitution
      at G453R. This amino acid is highly conserved among major fungal pathogens, and
      it is in a region very close to the heme-binding domain, which is characteristic
      of the cytochrome P450 superfamily, the primary target for the azole class of
      antifungal agents. This amino acid substitution may have caused the high
      resistance to azoles in T. asahii.

PMID- 22621705
TI  - "Effect of pranayama and meditation as an add-on therapy in rehabilitation of
      patients with Guillain-Barre syndrome--a randomized control pilot study".
AB  - OBJECTIVE: To study the add-on effects of pranayama and meditation in
      rehabilitation of patients with Guillain-Barre syndrome (GBS). PATIENTS AND
      METHOD: This randomized control pilot study was conducted in neurological
      rehabilitation unit of university tertiary research hospital. Twenty-two GBS
      patients, who consented for the study and satisfied selection criteria, were
      randomly assigned to yoga and control groups. Ten patients in each group
      completed the study. The yoga group received 15 sessions in total over a period
      of 3 weeks (1 h/session), one session per day on 5 days per week that consisted
      of relaxation, Pranayama (breathing practices) and Guided meditation in addition
      to conventional rehabilitation therapeutics. The control group received usual
      rehabilitation care. All the patients were assessed using Pittsburgh Sleep
      Quality Index, Numeric pain rating scale, Hospital anxiety and Depression scale
      and Barthel index score. Mann-Whitney U test and Wilcoxon's signed rank test were
      used for statistical analysis. RESULTS: Quality of sleep improved significantly
      with reduction of PSQI score in the yoga group (p = 0.04). There was reduction of
      pain scores, anxiety and depression in both the groups without statistical
      significance between groups (pain p > 0.05, anxiety p > 0.05 and depression p >
      0.05). Overall functional status improved in both groups without significant
      difference (p > 0.05). CONCLUSIONS: Significant improvement was observed in
      quality of sleep with yogic relaxation, pranayama, and meditation in GBS
      patients.

PMID- 22621706
TI  - Catalytic site-selective thiocarbonylations and deoxygenations of vancomycin
      reveal hydroxyl-dependent conformational effects.
AB  - We have examined peptide-based catalysts for the site-selective thiocarbonylation
      of a protected form of vancomycin. Several catalysts were identified that either
      enhanced or altered the inherent selectivity profile exhibited by the substrate.
      Two catalysts, one identified through screening and another through rational
      design, were demonstrated to be effective on 0.50-g scale. Deoxygenations led
      ultimately to two new deoxy-vancomycin derivatives, and surprising conformational
      consequences of deoxygenation were revealed for one of the new compounds. These
      effects were mirrored in the biological activities of the new analogues and
      support a structural role for certain hydroxyls in the native structure.

PMID- 22621707
TI  - Safety of peginterferon alfa-2a plus ribavirin in a large multinational cohort of
      chronic hepatitis C patients.
AB  - BACKGROUND & AIMS: Peginterferon plus ribavirin has been the standard of care for
      chronic hepatitis C for a decade and an essential component of combination
      regimens for this disease. This large multinational open-label study aimed to
      better define the incidence of serious adverse events (SAEs) and non-serious
      adverse events of special interest in patients receiving peginterferon alfa
      2a/ribavirin. METHODS: Patients were assigned at the investigator's discretion to
      24- or 48-week treatment with peginterferon alfa-2a 180 MUg/week and ribavirin
      800 mg/day or 1000/1200 mg/day. All AEs, defined as SAEs and non-SAEs of special
      interest, were recorded during treatment and for 12 weeks thereafter. Non-SAEs of
      special interest included those leading to dose reduction/discontinuation,
      neutropenia, thrombocytopenia, anaemia, ALT elevations leading to dose
      modification and unknown/unexpected AEs. RESULTS: Of 1675 and 7178 patients
      assigned to 24 and 48 weeks of treatment, respectively, 87.6 and 68.3% completed
      therapy, whereas 6.4 and 10.3% prematurely stopped peginterferon alfa-2a
      treatment because of AEs. Among patients assigned to 24 and 48 weeks, 37.4 and
      46.9%, respectively, reported any AE (SAE or non-SAE of special interest); 4.2
      and 6.6% reported SAEs and 35.2 and 44.0% reported non-SAEs of special interest.
      Female gender, increasing age and cirrhosis were significantly associated with
      dose reductions of either drug. Increasing age (and female gender in the case of
      ribavirin) was significantly associated with treatment discontinuation.
      CONCLUSION: This study confirmed the safety and tolerability profile of
      peginterferon alfa-2a/ribavirin and identified patient subgroups at higher risk
      of dose reductions and discontinuations, thus allowing optimum management of AEs.

PMID- 22621708
TI  - The secret story of fish: decreasing nutritional value due to pollution?

PMID- 22621709
TI  - Continued rise in the use of mid-level providers in US emergency departments,
      1993-2009.
AB  - BACKGROUND: Emergency department (ED) visits in the US have risen dramatically
      over the past 2 decades. In order to meet the growing demand, mid-level providers
      (MLPs) - both physician assistants (PAs) and nurse practitioners (NPs) - were
      introduced into emergency care. Our objective was to test the hypothesis that MLP
      usage in US EDs continues to rise. FINDINGS: We analyzed ED data from the
      National Hospital Ambulatory Medical Care Survey to identify trends in ED visits
      seen by MLPs. We also compared MLP-only visits (defined as visits where the
      patient was seen by a MLP without being seen by a physician) with those seen by
      physicians only. During 1993 to 2009, 8.4% (95%CI, 7.6-9.2%) of all US ED visits
      were seen by MLPs. These summary data include marked changes in MLP utilization:
      PA visits rose from 2.9% to 9.9%, while NP visits rose from 1.1% to 4.7% (both
      Ptrend < 0.001). Together, MLP visits accounted for almost 15% of 2009 ED visits
      and 40% of these were seen without involvement of a physician. Compared to
      physician only visits, those seen by MLPs only were less likely to arrive by
      ambulance (16% vs 6%) and be admitted (14% vs 3%). CONCLUSIONS: Mid-level
      provider use is rising in US EDs. By 2009, approximately one in seven visits
      involved MLPs, with PAs managing twice as many visits as NPs. Although patients
      seen by MLPs only are generally of lower acuity, these nationally representative
      data confirm that MLP care extends beyond minor presentations.

PMID- 22621710
TI  - Estimation of the severity of safety critical events.
AB  - Today, various measures are used to estimate the severity of a traffic conflict.
      However, these measures are all limited to estimating the crash risk and do not
      include any estimates of the possible consequences of a potential crash. In
      accident analysis the estimated severity of the event is related to the outcome
      of the crash, such as injury levels. This article proposes a new method for
      estimating the severity of safety critical events based on both an estimate of
      crash risk and an estimate of possible consequence that, in addition to a measure
      of safety margins, takes vehicle mass as well as the relative speed of the
      involved road users into consideration. The article compares the estimated
      severity of 61 conflicts and 9 accidents of the proposed method with the traffic
      conflict technique. The results from the severity estimates of our proposed
      method show a significant difference in the severity levels of events involving
      vehicles with similar mass compared to critical events involving vehicles with
      dissimilar mass and events involving pedestrians. The proposed method gives the
      possibility to compare different conflicts, with regard to severity, with each
      other regardless of what type of conflict it is, e.g. intersection or rural road,
      or what kind of road users that are involved. In addition, an event
      classification, i.e. serious or very serious event, based on the severity
      estimate of the proposed method, shows promising results indicating that the
      severities are estimated in a homogenous way. The article concludes that our
      proposed method of estimating the severity of critical event seems to be able to
      reflect the dangerousness in a more realistic way than the traffic conflict
      technique and should facilitate the development of traffic safety analysis
      methods.

PMID- 22621711
TI  - Gentiopicroside attenuates morphine rewarding effect through downregulation of
      GluN2B receptors in nucleus accumbens.
AB  - AIMS: Gentiopicroside (Gent) is one of the secoiridoid compound isolated from
      Gentiana lutea. This compound exhibits analgesic activities and inhibits the
      expression of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the
      anterior cingulate cortex in mice. Nucleus accumbens (NAc) is a forebrain
      structure known for its role in drug addiction. However, little is known about
      the role of Gent on morphine dependence and synaptic transmission changes in the
      NAc. METHODS: Conditioned place preference (CPP) test and behavioral
      sensitization of locomotor activity were used to investigate drug-seeking related
      behaviors. Brain slices containing NAc were prepared, and whole-cell patch-clamp
      recordings were performed to record the excitatory postsynaptic currents (EPSCs).
      Expression of proteins was detected by Western blot analysis. RESULTS: Systemic
      administration of Gent attenuated the CPP effect induced by morphine, but had no
      effect on morphine-induced behavioral sensitization. Gent significantly reversed
      overexpression of GluN2B-containing NMDA receptors and dopamine D2 receptors in
      NAc during the first week of morphine withdrawal. However, the compound did not
      affect the overexpression of GluN2A-containing NMDA receptors, GluA1, and
      dopamine D1 receptors. Lastly, Gent significantly reduced NMDA receptors-mediated
      EPSCs in the NAc. CONCLUSION: Our study provides strong evidence that Gent
      inhibits morphine dependence through downregulation of GluN2B-containing NMDA
      receptors in the NAc.

PMID- 22621712
TI  - [Influence of systemic corticosteroid administration in the prognosis of patients
      with community-acquired pneumonia].
AB  - INTRODUCTION: Community-acquired pneumonia (CAP) is a common and potentially
      serious disease. In recent years, control of the inflammatory response has begun
      to be taken into account as a new therapeutic target. This study has aimed to
      analyze the influence of the administration of systemic corticosteroids on
      mortality of patients admitted with CAP in the common clinical practice. PATIENTS
      AND METHODS: A prospective observational study was carried out. The study
      included patients with CAP admitted to Internal Medicine and Pulmonology services
      of a tertiary hospital in 2007. Treatment given during admission was recorded and
      mortality during hospitalization and at 30 and 90 days after discharge was
      determined. RESULTS: A total of 257 patients, 179 men (69.6%) and 78 women
      (30.4%) were analyzed. Mean age was 72+/-15 years. Both in-hospital mortality as
      well as at 30 days of discharge was 10.2%, while overall mortality at 90 days was
      14.8%. No relation was found between the use of corticosteroids and mortality.
      Use of corticosteroids also did not modify the length of hospital stay or
      readmission rate. CONCLUSIONS: It was observed in this study that treatment with
      corticosteroids in CAP is not associated with lower mortality and does not affect
      the rate of readmissions. It also does not change the length of hospital stay.

PMID- 22621713
TI  - [News on venous thromboembolic disease].
AB  - This paper brings together the latest developments that have occurred in
      different aspects of venous thromboembolism (VTE): VTE prophylaxis in high-risk
      orthopedic surgery and acutely ill hospitalized medical patients; therapeutic
      advances in pulmonary embolism and superficial vein thrombosis and VTE future
      prospects. It summarizes the reviews that five speakers made in-depth for the
      Second Day in New Anticoagulant Treatment, held in Madrid on November 18, 2011,
      organized by the Foundation for the Study of Thromboembolic Disease in Spain and
      endorsed by the Spanish Society of Internal Medicine, Spanish Society of
      Pneumology and Thoracic Surgery, Spanish Society of Cardiology, Spanish Society
      of Thrombosis and Haemostasis and the Spanish Society of Angiology and Vascular
      Surgery.

PMID- 22621714
TI  - Gold(I) carbene complexes causing thioredoxin 1 and thioredoxin 2 oxidation as
      potential anticancer agents.
AB  - Gold(I) complexes with 1,3-substituted imidazole-2-ylidene and benzimidazole-2
      ylidene ligands of the type NHC-Au-L (NHC = N-heterocyclic carbene L = Cl or 2
      mercapto-pyrimidine) have been synthesized and structurally characterized. The
      compounds were evaluated for their antiproliferative properties in human ovarian
      cancer cells sensitive and resistant to cisplatin (A2780S/R), as well in the
      nontumorigenic human embryonic kidney cell line (HEK-293T), showing in some cases
      important cytotoxic effects. Some of the complexes were comparatively tested as
      thioredoxin reductase (TrxR) and glutathione reductase (GR) inhibitors, directly
      against the purified proteins or in cell extracts. The compounds showed potent
      and selective TrxR inhibition properties in particular in cancer cell lines.
      Remarkably, the most effective TrxR inhibitors induced extensive oxidation of
      thioredoxins (Trxs), which was more relevant in the cancerous cells than in HEK
      293T cells. Additional biochemical assays on glutathione systems and reactive
      oxygen species formation evidenced important differences with respect to the
      classical cytotoxic Au(I)-phosphine compound auranofin.

PMID- 22621715
TI  - Translating evidence-based guidelines into practice: a survey of practices of
      commissioners and managers of the English stop smoking services.
AB  - BACKGROUND: The English National Health Service's (NHS) Stop Smoking Services
      (SSSs) constitute one of the most highly developed behavioural support programmes
      in the world. However, there is significant variation in success rates across the
      approximately 150 services, some of which may be due to variation in practice.
      This study aimed to assess these differences in practice. METHODS: Two online
      surveys were administered. All commissioners (people who purchase services for
      the NHS) and managers (those who run the services) of NHS SSSs in England were
      invited to participate. Items included details of current practices and services
      provided, what informed the commissioning of SSSs, what targets were included
      within service specifications and whether the types of treatment model to be
      delivered were specified. RESULTS: Both surveys had a response rate of 35%, with
      50 commissioners and 58 managers participating. There were no significant
      differences between the characteristics of the Primary Care Trusts (PCTs) from
      which commissioners and managers responded to this survey and those PCTs from
      which there was no response. Managers reported that the treatment model most
      frequently offered by SSSs was one-to-one (98%). A total of 16% of managers
      reported that some approved medications were not available as first-line
      treatments. Just over one third (38%) of commissioners reported consulting
      national guidelines or best evidence to inform local commissioning. Almost one
      third (30%) of commissioners reported that they specified the types of stop
      smoking interventions to be delivered by the providers. CONCLUSIONS: A
      substantial part of commissioning of Stop Smoking Services in England appears to
      take place without adequate consultation of evidence-based guidelines or
      specification of the service to be provided. This may account for at least some
      of the variation in success rates.

PMID- 22621716
TI  - CT-Screening for lung cancer does not increase the use of anxiolytic or
      antidepressant medication.
AB  - BACKGROUND: CT screening for lung cancer has recently been shown to reduce lung
      cancer mortality, but screening may have adverse mental health effects. We
      calculated risk ratios for prescription of anti-depressive (AD) or anxiolytic
      (AX) medication redeemed at Danish pharmacies for participants in The Danish Lung
      Cancer Screening Trial (DLCST). METHODS: The DLCST was a randomized clinical
      trial which comprised 4,104 former or present smokers who were randomized from 12
      May 2004 to 20 June 2006 to either CT scan of the chest, lung-function test and
      filling in questionnaires annually for five years in the period 1 April 2006-31
      March 2010 (n = 2,052), or to a control group (n = 2,052) receiving similar
      procedures except CT scan. We used CT scan intervention group versus control
      group status as exposure. The follow-up period for use of AD or AX was three
      years. Baseline data on civil status, socioeconomic status, and co-morbidity as
      well as outcome data on AD and AX were obtained by linkage to national
      registries. RESULTS: The intervention and the control groups did not differ by
      age, gender, civil status, socio-economic position, co-morbidity index or former
      use of AD or AX. The adjusted risk ratio for at least one recipe of AD or AX in
      the CT intervention group during follow-up was not increased when adjusting for
      previous use of AD or AX, HR 1.00, 95 % CI (0.90-1.12). Similar results were seen
      when excluding subjects using AD or AX in a four-month or two-year period before
      baseline, when analyzing AD and AX separately, or requiring at least two recipes.
      CONCLUSIONS: We found no indications that participation in a lung cancer CT
      screening program increases the risk of specific adverse mental health outcomes.
      TRIAL REGISTRATION: Clinical Trials.gov Protocol Registration System
      (NCT00496977).

PMID- 22621717
TI  - Woven right coronary artery.
AB  - Woven coronary artery is characterized by the twisting course of multiple thin
      channels along the vessel in any coronary artery with a TIMI-III blood flow. It
      is an extremely rare coronary anomaly, which is generally considered to be
      benign. We present a 48-year-old male patient with a woven coronary artery
      anomaly with a right woven who presented with a myocardial infarction and review
      the literature on this coronary anomaly.

PMID- 22621718
TI  - The year in review: surgical revascularization of coronary artery disease--2011.
AB  - Important studies highlighting the practice of coronary artery bypass surgery for
      2011 are reviewed.

PMID- 22621720
TI  - Aortic dissection and recurrence both precipitated by sexual activity.
AB  - Risk factors for aortic dissection include: hypertension, connective tissue
      disorders, chronic obstructive pulmonary diseases, and severe physical and
      emotional stress. Although dissection associated with extreme physical activity
      has been reported, to date, there have been no reports in the literature to our
      knowledge of acute dissection and recurrence both occurring during sexual
      activity. We report a case of a 34-year-old male who underwent emergency
      replacement of his aortic root and hemiarch for an aortic dissection precipitated
      by sexual intercourse.

PMID- 22621719
TI  - Ministernotomy with subclavian extension for the management of a large
      intrathoracic pseudoaneurysm.
AB  - We report on the management of a large intrathoracic subclavian pseudoaneurysm
      treated using an upper J ministernotomy with subclavian extension. This approach
      allows exposure of the supraaortic vessels and upper portion of the thoracic
      cavity and may be of help in selected cases.

PMID- 22621721
TI  - Staged repair of pentalogy of Cantrell with ectopia cordis and ventricular septal
      defect.
AB  - Pentalogy of Cantrell is a rare congenital anomaly characterized by a combination
      of severe defects in the middle of the chest and abdomen including intracardiac
      defects. Survival rate after cardiac surgery is extremely low. We present a
      successful staged complete repair of an omphalocele, a ventricular septal defect
      and a sternal defect in a case of pentalogy of Cantrell.

PMID- 22621723
TI  - Severe aortic insufficiency secondary to 5L Impella device placement.
AB  - This case report describes the case of a 45-year-old female with a heart
      transplant who developed severe aortic insufficiency after insertion of a 5L
      Impella device. The case is unusual as there has been no published report of
      aortic valve injury leading to persistent and significant aortic regurgitation
      after insertion of an Impella device.

PMID- 22621724
TI  - Accumulation of six metals in the mangrove crab Ucides cordatus (Crustacea:
      Ucididae) and its food source, the red mangrove Rhizophora mangle (Angiosperma:
      Rhizophoraceae).
AB  - The crab Ucides cordatus and the red mangrove Rhizophora mangle are endemic
      mangrove species and potential bio-accumulators of metals. This study quantified
      the accumulation of six metals (Cd, Cr, Cu, Hg, Mn and Pb) in different organs
      (claw muscle, hepatopancreas and gills) of U. cordatus, as well as in different
      maturation stages of the leaves (buds, green mature, and pre-abscission
      senescent) of R. mangle. Samples were collected from mangrove areas in Cubatao,
      state of Sao Paulo, a heavily polluted region in Brazil. Data for metal contents
      in leaves were evaluated by one-way ANOVA; while for crabs a factorial ANOVA was
      used to investigate the effect of different tissues, animal size and the
      interactions between them. Means were compared by Tukey test at five percent, and
      the association between the metal concentrations in each crab organ, depending on
      the size, was evaluated by Pearson's linear correlation coefficient (r).
      Concentrations of Pb and Hg were undetectable for the different leaf stages and
      crab tissues, while Cd concentrations were undetectable in the leaf stages. In
      general, the highest accumulation of metals in R. mangle leaves occurred in pre
      abscission senescent and green mature leaves, except for Cu, which was found in
      the highest concentrations in buds and green mature leaves. For the crab, Cd, Cu,
      Cr and Mn were present in concentrations above the detection limit, with the
      highest accumulation in the hepatopancreas, followed by the gills. Cu was
      accumulated mostly in the gills. Patterns of bioaccumulation between the crab and
      the mangrove tree differed for each metal, probably due to the specific
      requirements of each organism for essential metals. However, there was a close
      and direct relationship between metal accumulation in the mangrove trees and in
      the crabs feeding on them. Tissues of R. mangle leaves and U. cordatus proved
      effective for monitoring metals, acting as important bioindicators of mangrove
      areas contaminated by various metals.

PMID- 22621725
TI  - From the ORFeome concept to highly comprehensive, full-genome screening
      libraries.
AB  - Recombination-based cloning techniques have in recent times facilitated the
      establishment of genome-scale single-gene ORFeome repositories. Their further
      handling and downstream application in systematic fashion is, however,
      practically impeded because of logistical plus economic challenges. At this
      juncture, simultaneously transferring entire gene collections in compiled pool
      format could represent an advanced compromise between systematic ORFeome (an
      organism's entire set of protein-encoding open reading frames) projects and
      traditional random library approaches, but has not yet been considered in great
      detail. In our endeavor to merge the comprehensiveness of ORFeomes with a
      basically simple, streamlined, and easily executable single-tube design, we have
      here produced five different pooled screening-ready libraries for both
      Staphylococcus aureus and Homo sapiens. By evaluating the parallel transfer
      efficiencies of differentially sized genes from initial polymerase chain reaction
      (PCR) product amplification to entry and final destination library construction
      via quantitative real-time PCR, we found that the complexity of the gene
      population is fairly stably maintained once an entry resource has been
      successfully established, and that no apparent size-selection bias loss of large
      inserts takes place. Recombinational transfer processes are hence robust enough
      for straightforwardly achieving such pooled screening libraries.

PMID- 22621727
TI  - Evaluation of "the incredible years" in Sweden: the transferability of an
      American parent-training program to Sweden.
AB  - Structured parent training has been proven to be effective in reducing disruptive
      behavior problems (DBP) in children. Most of the programs that are used in Sweden
      have their origin in North America, and there is an ongoing debate over the
      transferability to Sweden of manual-based programs developed in other contexts.
      The goal of the present study was to study effectiveness of the Incredible Years
      parent-training program (IY), developed in the US, in regular clinical work in
      Sweden, using a randomized controlled design. Parents of 62 four to eight-year
      old children diagnosed with Oppositional Defiant Disorder participated in the
      study. Parents of 38 children were assigned to parent training (PT) and 24 to a
      waiting list (WL). The results indicate that the IYS retains the positive effects
      on children's disruptive behavior problems when translated and transferred to
      Swedish. There was a statistically significant difference in reduction of DBP in
      children between the groups in favor of the PT. The improvement in the PT group
      was sustained at the one-year follow-up. The improvement also, at least to some
      extent, generalized over time to the school context. There was also a
      statistically significant difference in mothers' report of pre to post change in
      parenting alliance between the PT and WL groups. The IYS program was appreciated
      and well received by the participating mothers.

PMID- 22621726
TI  - A new approach for detecting low-level mutations in next-generation sequence
      data.
AB  - We propose a new method that incorporates population re-sequencing data,
      distribution of reads, and strand bias in detecting low-level mutations. The
      method can accurately identify low-level mutations down to a level of 2.3%, with
      an average coverage of 500*, and with a false discovery rate of less than 1%. In
      addition, we also discuss other problems in detecting low-level mutations,
      including chimeric reads and sample cross-contamination, and provide possible
      solutions to them.

PMID- 22621729
TI  - Ultrasound mediated drug delivery: a 21st century phoenix?

PMID- 22621728
TI  - Zuckerman-Kuhlman-Aluja Personality Questionnaire (ZKA-PQ) and Cloninger's
      Temperament and Character Inventory Revised (TCI-R): a comparative study.
AB  - The aim of this study was to compare the psychometric properties (normal
      distribution values, reliabilities and factor structure) of the Zuckerman-Kuhlman
      Aluja Personality Questionnaire (ZKA-PQ) and the Temperament and Character
      Inventory revised (TCI-R). The total sample consisted of 482 subjects (53.1% men
      and 46.9% women) from diverse age. Results showed somewhat better psychometric
      properties, like reliability and facet-factor structure, for the ZKA-PQ than the
      TCI-R. The expected five-factor facet structure of the ZKA-PQ was clear found.
      However, the seven-factor structure of TCI-R was not clear and it did not show a
      clear distinction between Temperament and Character factors. When ZKA-PQ and TCI
      R variables are analyzed together, the ZKA-PQ factors are related to the
      Character as well as the Temperament factors. In some cases they represent the
      opposite poles of ZKA-PQ factors; for example, Neuroticism versus Self
      Directiveness and Aggression versus Cooperativeness. Some are directly and highly
      related to ZKA-PQ factors; for example, Sensation Seeking and Novelty Seeking,
      Extraversion and Reward Dependence, Neuroticism and Harm Avoidance, and Activity
      and Persistence.

PMID- 22621730
TI  - Use of ultrasound in drug delivery systems: emphasis on experimental methodology
      and mechanisms.
AB  - Recent studies have shown that ultrasound energy could be applied for targeting
      or controlling drug release. This new concept of therapeutic ultrasound combined
      with drugs has induced a great amount of interest in various medical fields. In
      this paper, several experimental systems are cited in which ultrasound is being
      utilized to evaluate new application of this modality. The mechanisms of
      ultrasound-mediated drug delivery are discussed in addition to the review of
      current advances in the use of ultrasound in systems involving research in cancer
      therapy, gene therapy, microbubbles and other drug delivery in vitro and in vivo
      experiments.

PMID- 22621731
TI  - Ultrasound-mediated gene transfection in vitro: effect of ultrasonic parameters
      on efficiency and cell viability.
AB  - Ultrasound (US)-mediated gene transfection in the presence of microbubbles is a
      recently developed and promising non-viral gene delivery method. Optimising the
      parameters used in ultrasonic transfection is urgently required in order to
      realise higher transfection efficiencies in clinical settings. This study
      examined the effect of ultrasound exposure parameters on plasmid DNA transfection
      in mouse embryonic fibroblast cell lines using perfluorobutane bubbles.
      Variations in US intensity (0-11 W/cm2), pulse repetition frequency (PRF, 50
      50,000 Hz), duty ratio (10 to 50%), exposure time (0-120 s) and microbubble
      volume concentration (0 to 10%) were tested, and the microbubble volume
      concentration was also monitored during exposure. Through the experiments, the
      mechanism of how variations in parameters influence US-mediated gene transfection
      was discussed, which can provide a basis for future applications of ultrasound
      mediated transfection.

PMID- 22621732
TI  - Microbubble-enhanced ultrasound-mediated gene transfer--towards the development
      of targeted gene therapy for cancer.
AB  - Ultrasound-mediated gene transfer is emerging as a possible alternative to viral
      gene transfer, and pre-clinical data suggest that it may play a significant role
      in gene therapy-based approaches to the treatment of disease. As an
      extracorporeal stimulus, ultrasound can non-invasively and transiently compromise
      cell membrane permeability (sonoporation), thereby offering the promise of
      delivering either genes or oligonucleotide-based therapeutics to cells and
      tissues in a site-specific manner. The membrane-permeabilising effects of
      ultrasound can be greatly enhanced using microbubble preparations, many of which
      have, in the past, found application as ultrasound contrast agents. Because these
      ultrasound-responsive agents are highly amenable to surface modification it has
      been suggested that they may be exploited as ultrasound-responsive nucleic acid
      delivery vehicles. In this article we seek to explore the potential role
      ultrasound, in combination with microbubble-based agents, may play in providing
      site-specific gene therapy-based approaches for the treatment of cancer.

PMID- 22621733
TI  - Ultrasound-induced cell permeabilisation and hyperthermia: strategies for local
      delivery of compounds with intracellular mode of action.
AB  - There is an increasing clinical need for novel, externally triggered, local drug
      delivery methods since many drugs are characterised by high systemic toxicity
      and/or suffer from limited bioavailability. Thermosensitive liposomes (TSLs)
      demonstrate great potential for local delivery and release of the payload. They
      are particularly effective in combination with ultrasound (US) under magnetic
      resonance (MR) guidance that is known to induce hyperthermia locally in a
      precisely controlled manner. Bioeffects of hyperthermia include increased blood
      flow, blood volume and enhanced vascular permeability thus potentiating anti
      tumoural efficacy of TSLs. However, bioeffects of ultrasound are not limited to
      hyperthermia only, and under certain parameters may include locally enhanced
      extravasation and permeabilisation of cell membrane for compounds. This opens up
      opportunities for delivery of cell-impermeable and weakly permeable drugs that
      can be employed together with thermosensitive liposomes. In the latter case US
      mediated cavitation and/or radiation forces local permeabilisation of the cells
      and US-induced hyperthermia releases the drug. This review focuses on bioeffects
      of US such as hyperthermia, enhanced extravasation and cell permeabilisation
      utilised for local drug delivery.

PMID- 22621734
TI  - Mild hyperthermia with magnetic resonance-guided high-intensity focused
      ultrasound for applications in drug delivery.
AB  - PURPOSE: Mild hyperthermia (40-45  degrees C) is a proven adjuvant for
      radiotherapy and chemotherapy. Magnetic resonance guided high intensity focused
      ultrasound (MR-HIFU) can non-invasively heat solid tumours under image guidance.
      Low temperature-sensitive liposomes (LTSLs) release their drug cargo in response
      to heat (>40  degrees C) and may improve drug delivery to solid tumours when
      combined with mild hyperthermia. The objective of this study was to develop and
      implement a clinically relevant MR-HIFU mild hyperthermia heating algorithm for
      combination with LTSLs. MATERIALS AND METHODS: Sonications were performed with a
      clinical MR-HIFU platform in a phantom and rabbits bearing VX2 tumours (target =
      4-16 mm). A binary control algorithm was used for real-time mild hyperthermia
      feedback control (target = 40-41  degrees C). Drug delivery with LTSLs was
      measured with HPLC. Data were compared to simulation results and analysed for
      spatial targeting accuracy (offset), temperature accuracy (mean), homogeneity of
      heating (standard deviation (SD), T10 and T90), and thermal dose (CEM43).
      RESULTS: Sonications in a phantom resulted in better temperature control than in
      vivo. Sonications in VX2 tumours resulted in mean temperatures between 40.4 
      degrees C and 41.3  degrees C with a SD of 1.0-1.5  degrees C (T10 = 41.7-43.7 
      degrees C, T90 = 39.0-39.6  degrees C), in agreement with simulations. 3D spatial
      offset was 0.1-3.2 mm in vitro and 0.6-4.8 mm in vivo. Combination of MR-HIFU
      hyperthermia and LTSLs demonstrated heterogeneous delivery to a partially heated
      VX2 tumour, as expected. CONCLUSIONS: An MR-HIFU mild hyperthermia heating
      algorithm was developed, resulting in accurate and homogeneous heating within the
      targeted region in vitro and in vivo, which is suitable for applications in drug
      delivery.

PMID- 22621735
TI  - Targeted drug delivery by high intensity focused ultrasound mediated hyperthermia
      combined with temperature-sensitive liposomes: computational modelling and
      preliminary in vivovalidation.
AB  - PURPOSE: To develop and validate a computational model that simulates (1) tissue
      heating with high intensity focused ultrasound (HIFU), and (2) resulting
      hyperthermia-mediated drug delivery from temperature-sensitive liposomes (TSL).
      MATERIALS AND METHODS: HIFU heating in tissue was simulated using a heat transfer
      model based on the bioheat equation, including heat-induced cessation of
      perfusion. A spatio-temporal multi-compartment pharmacokinetic model simulated
      intravascular release of doxorubicin from TSL, its transport into interstitium,
      and cell uptake. Two heating schedules were simulated, each lasting 30 min: (1)
      hyperthermia at 43  degrees C (HT) and (2) hyperthermia followed by a high
      temperature (50  degrees C for 20 s) pulse (HT+). As preliminary model
      validation, in vivo studies were performed in thigh muscle of a New Zealand White
      rabbit, where local hyperthermia with a clinical magnetic resonance-guided HIFU
      system was applied following TSL administration. RESULTS: HT produced a defined
      region of high doxorubicin concentration (cellular concentration ~15-23 ug/g) in
      the target region. Cellular drug uptake was directly related to HT duration, with
      increasing doxorubicin uptake up to ~2 h. HT+ enhanced drug delivery by ~40%
      compared to HT alone. Temperature difference between model and experiment within
      the hyperthermia zone was on average 0.54  degrees C. Doxorubicin concentration
      profile agreed qualitatively with in vivo fluorescence profile. CONCLUSIONS:
      Computational models can predict temperature and delivered drug from combination
      of HIFU with TSL. Drug delivery using TSL may be enhanced by prolonged
      hyperthermia up to 2 h or by local cessation of vascular perfusion with a high
      temperature pulse following hyperthermia.

PMID- 22621736
TI  - Gene transfection enhanced by ultrasound exposure combined with drug treatment
      guided by gene chip analysis.
AB  - PURPOSE: Heterogeneous bioeffects have been reported in previous studies of
      ultrasound-mediated gene delivery. The goal of this study is to identify the
      differences between cells that take up plasmid DNA (pDNA) after sonication but
      are not transfected and cells that similarly take up pDNA but are transfected. We
      used these findings to select drugs that regulate intracellular processes
      expected to enhance gene transfection in combination with US. MATERIALS AND
      METHODS: Gene expression among DU145 human prostate cancer cells after ultrasound
      mediated transfection was analyzed using Affymetrix GeneChip Human Genome U133
      Plus 2.0 Arrays. Drug treatments suggested by the microarray analysis were
      combined with US exposure to regulate the corresponding intracellular processes.
      Cell viability and transfection efficiency were determined by flow cytometry to
      analyze the effects of US combined with drug treatment. RESULTS: Genes such as
      GADD45alpha (growth arrest and DNA-damage inducible, alpha) and Topoisomerase
      IIalpha were found to be associated with successful transfection. Drugs that
      regulate GADD45alpha and Topoisomerase IIalpha (e.g., ethyl methanesulfomate,
      amsacrine and chloroquine) were shown to increase ultrasound-mediated
      transfection efficiency by up to 2 fold. CONCLUSIONS: Among cells with pDNA
      uptake after sonication, we found that genes are differentially expressed among
      transfected cells versus non-transfected cells. Regulation of the expression
      level of GADD45alpha and TOP2alpha and other intracellular processes can yield
      higher efficiency of ultrasound-mediated gene transfection. This suggests that a
      strategy to increase gene transfection efficiency involving the combination of
      sonication and regulation of intracellular processes using drugs could further
      enhance US-mediated gene transfection.

PMID- 22621737
TI  - Magnetic targeting and ultrasound mediated drug delivery: benefits, limitations
      and combination.
AB  - This paper reviews the uses of magnetism and ultrasound in therapeutic delivery
      applications. Emphasis is placed upon magnetic nanoparticles and microbubble
      ultrasound contrast agents. The underlying physical principles, history, key
      developments and limitations of these techniques for drug and gene delivery in
      vitro and in vivo are explored. The combination of ultrasonic and magnetic
      techniques is also reviewed with particular focus on magnetic microbubbles as
      delivery agents with the potential to combine the advantages of both methods
      whilst addressing many of their limitations. Finally, results are presented from
      a study of a new magnetic microbubble formulation which shows great applicability
      as a therapeutic delivery vehicle.

PMID- 22621738
TI  - Ultrasound-mediated micellar drug delivery.
AB  - During the last decade, nanomedicine has emerged as a new field of medicine that
      utilises nanoscale materials for delivery of drugs, genes and imaging agents. The
      efficiency of drug delivery may be enhanced by the application of directed
      energy, which provides for drug targeting and enhanced intracellular uptake. In
      this paper, we present a review of recent advances in the ultrasound-mediated
      drug delivery with the emphasis on polymeric micelles as tumour-targeted drug
      carriers. This new modality of drug targeting to tumours is based on the drug
      encapsulation in polymeric micelles followed by a localised release at the tumour
      site triggered by focused ultrasound. The rationale behind this approach is that
      drug encapsulation in micelles decreases systemic concentration of free drug and
      provides for a passive drug targeting to tumours via the enhanced permeability
      and retention (EPR) effect, therefore reducing unwanted drug interactions with
      healthy tissues. Ultrasound affects micellar drug delivery on various levels.
      Mild hyperthermia induced by ultrasound may enhance micelle extravasation into
      tumour tissue; mechanical action of ultrasound results in drug release from
      micelles and enhances the intracellular uptake of both released and encapsulated
      drug. In addition, polymeric micelles sensitise multidrug resistant (MDR) cells
      to the action of drugs.

PMID- 22621740
TI  - Taboos and opportunities in sonothrombolysis for stroke.
AB  - Systemic thrombolysis with tissue plasminogen activator (tPA) is the only
      approved treatment for acute ischaemic stroke that improves functional outcome if
      given up to 4.5 h from symptom onset. At least half of treated patients have
      unfavourable outcomes long-term though, emphasising the need to amplify the only
      approved acute stroke therapy. Ultrasound targeting of an intra-arterial
      occlusive clot and delivering mechanical pressure to its surrounding fluids
      (referred to as sonothrombolysis) accelerates the thrombolytic effect of tPA.
      Higher recanalisation rates produce a trend towards better functional outcomes
      that could be safely achieved with the combination of 2 MHz frequency ultrasound
      and systemic tPA. To further accelerate the clot-dissolving effect of ultrasound,
      a variety of frequencies and intensities as well as other adjuvant treatment
      elements are being studied. However, literature reports argue efficacy and safety
      of these novel approaches doubting promptly translation into the clinical
      practice. This review will summarise our current knowledge about potentially
      harmful (taboos) directions and what we think are promising avenues for these
      future stroke therapies. We also give a prospect for novel technologies such as
      operator-independent devices that aim to further spread the use of
      sonothrombolysis for stroke.

PMID- 22621741
TI  - Therapeutic applications of ultrasound in ophthalmology.
AB  - Therapeutic ultrasound, although less well known than ultrasound for diagnostic
      imaging, has become a topic of growing interest in ophthalmology. High intensity
      focused ultrasound (HIFU) for the treatment of glaucoma and ultrasonic drug
      delivery are the two main areas of research and potential clinical applications.
      For the treatment of glaucoma, the specific advantage of HIFU, particularly when
      compared to the laser, is that the energy can be focused through optically opaque
      media, especially through the sclera which is a strongly light-scattering medium.
      HIFU is therefore a possible method for partial coagulation of the ciliary body
      (an anatomical structure responsible for the production of the liquid filling the
      eye) and, hence, reducing intraocular pressure and the risk of glaucoma. Ocular
      drug bioavailability also remains a challenge, being limited by multiple barriers
      to drug entry and lacrimal drainage, and making it difficult to achieve a
      sufficient drug concentration for numerous diseases of the front and back of the
      eye. As the front wall of the eye (cornea and anterior sclera) is a pathway for
      topically applied drugs, locally applied ultrasound has been proposed as a way of
      enhancing the delivery and activity of drugs and genes. Despite the fact that
      experimental studies seem to confirm the potential benefit of ultrasound ocular
      drug delivery, there is still a lack of clinical evidence. The aim of this
      contribution is to provide an update on recent advances in the field of
      therapeutic ultrasound in ophthalmology.

PMID- 22621739
TI  - Ultrasound enhanced drug delivery to the brain and central nervous system.
AB  - There is an increasing interest in the use of ultrasound to enhance drug delivery
      to the brain and central nervous system. Disorders of the brain and CNS
      historically have had poor response to drug therapy due to the presence of the
      blood-brain barrier (BBB). Techniques for circumventing the BBB are typically
      highly invasive or involve disrupting large portions of the BBB, exposing the
      brain to pathogens. Ultrasound can be non-invasively delivered to the brain
      through the intact skull. When combined with preformed microbubbles, ultrasound
      can safely induce transient, localised and reversible disruption of the BBB,
      allowing therapeutics to be delivered. Investigations to date have shown positive
      response to ultrasound BBB disruption combined with therapeutic agent delivery in
      rodent models of primary and metastatic brain cancer and Alzheimer's disease.
      Recent work in non-human primates has demonstrated that the technique is feasible
      for use in humans. This review examines the current status of drug delivery to
      the brain and CNS both by disruption of the BBB, and by ultrasound enhancement of
      drug delivery through the already compromised BBB. Cellular and physical
      mechanisms of disruption are discussed, as well as treatment technique, safety
      and monitoring.

PMID- 22621743
TI  - Role of satellite cells in muscle growth and maintenance of muscle mass.
AB  - Changes in muscle mass may result from changes in protein turnover, reflecting
      the balance between protein synthesis and protein degradation, and changes in
      cell turnover, reflecting the balance between myonuclear accretion and myonuclear
      loss. Myonuclear accretion, i.e. increase in the number of myonuclei within the
      muscle fibers, takes place via proliferation and fusion of satellite cells,
      myogenic stem cells associated to skeletal muscle fibers and involved in muscle
      regeneration. In developing muscle, satellite cells undergo extensive
      proliferation and most of them fuse with myofibers, thus contributing to the
      increase in myonuclei during early postnatal stages. A similar process is induced
      in adult skeletal muscle by functional overload and exercise. In contrast,
      satellite cells and myonuclei may undergo apoptosis during muscle atrophy,
      although it is debated whether myonuclear loss occurs in atrophying muscle. An
      increase in myofiber size can also occur by changes in protein turnover without
      satellite cell activation, e.g. in late phases of postnatal development or in
      some models of muscle hypertrophy. The relative role of protein turnover and cell
      turnover in muscle adaptation and in the establishment of functional muscle
      hypertrophy remains to be established. The identification of the signaling
      pathways mediating satellite cell activation may provide therapeutic targets for
      combating muscle wasting in a variety of pathological conditions, including
      cancer cachexia, renal and cardiac failure, neuromuscular diseases, as well as
      aging sarcopenia. 

PMID- 22621744
TI  - Community perspectives on roles and responsibilities for strengthening primary
      health care in rural Ethiopia.
AB  - Government-community partnerships are central to developing effective,
      sustainable models of primary health care in low-income countries; however,
      evidence about the nature of partnerships lacks the perspective of community
      members. Our objective was to characterise community perspectives regarding the
      respective roles and responsibilities of government and the community in efforts
      to strengthen primary health care in low-income settings. We conducted a
      qualitative study using focus groups (n=14 groups in each of seven primary health
      care units in Amhara and Oromia, Ethiopia, with a total of 140 participants) in
      the context of the Ethiopian Millennium Rural Initiative. Results indicated that
      community members defined important roles and responsibilities for both
      communities and governments. Community roles included promoting recommended
      health behaviours; influencing social norms regarding health; and contributing
      resources as feasible. Government roles included implementing oversight of health
      centres; providing human resources, infrastructure, equipment, medication and
      supplies; and demonstrating support for community health workers, who are seen as
      central to the rural health system. Renewed efforts in health system
      strengthening highlight the importance of community participation in initiatives
      to improve primary health care in rural settings. Community perspectives provide
      critical insights to defining, implementing and sustaining partnerships in these
      settings.

PMID- 22621745
TI  - Hospital costs of nosocomial multi-drug resistant Pseudomonas aeruginosa
      acquisition.
AB  - BACKGROUND: We aimed to assess the hospital economic costs of nosocomial multi
      drug resistant Pseudomonas aeruginosa acquisition. METHODS: A retrospective study
      of all hospital admissions between January 1, 2005, and December 31, 2006 was
      carried out in a 420-bed, urban, tertiary-care teaching hospital in Barcelona
      (Spain). All patients with a first positive clinical culture for P. aeruginosa
      more than 48 h after admission were included. Patient and hospitalization
      characteristics were collected from hospital and microbiology laboratory
      computerized records. According to antibiotic susceptibility, isolates were
      classified as non-resistant, resistant and multi-drug resistant. Cost estimation
      was based on a full-costing cost accounting system and on the criteria of
      clinical Activity-Based Costing methods. Multivariate analyses were performed
      using generalized linear models of log-transformed costs. RESULTS: Cost
      estimations were available for 402 nosocomial incident P. aeruginosa positive
      cultures. Their distribution by antibiotic susceptibility pattern was 37.1% non
      resistant, 29.6% resistant and 33.3% multi-drug resistant. The total mean
      economic cost per admission of patients with multi-drug resistant P. aeruginosa
      strains was higher than that for non-resistant strains (15,265 vs. 4,933 Euros).
      In multivariate analysis, resistant and multi-drug resistant strains were
      independently predictive of an increased hospital total cost in compared with non
      resistant strains (the incremental increase in total hospital cost was more than
      1.37-fold and 1.77-fold that for non-resistant strains, respectively).
      CONCLUSIONS: P. aeruginosa multi-drug resistance independently predicted higher
      hospital costs with a more than 70% increase per admission compared with non
      resistant strains. Prevention of the nosocomial emergence and spread of
      antimicrobial resistant microorganisms is essential to limit the strong economic
      impact.

PMID- 22621746
TI  - Oral versus inhaled ribavirin therapy for respiratory syncytial virus infection
      after lung transplantation.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is a significant contributor to
      morbidity in adult lung transplant recipients. Multiple modes of ribavirin
      administration have been described in the literature. This study investigated
      outcomes related to delivery route. METHODS: We performed a retrospective
      analysis of adult lung transplant patients infected with RSV (2006-2010). RSV
      severity was graded according to clinical symptoms and bronchiolitis obliterans
      syndrome (BOS) status on International Society for Heart and Lung Transplantation
      (ISHLT) criteria. Relationships between route of ribavirin delivery and RSV
      severity, BOS progression at 6 months after RSV infection, and overall survival
      were assessed. Of 30 RSV-positive patients identified, 9 were ultimately
      excluded. RESULTS: The 21 study patients were a mean age of 49 +/- 17 years
      (range, 17-72 years) at transplant. Six received oral and 15 received inhaled
      ribavirin per clinician preference. No significant differences were observed
      between the groups by age, sex, or ethnicity. Mean time from transplant to RSV
      was 26 +/- 29 months (range, 1-100 months). Infections were mild in 2 of 6
      patients in the oral compared with 11 of 15 in the inhaled group (p = 0.17). None
      of the oral group and 3 of the inhaled group exhibited BOS 1 at time of infection
      (p = 0.53); 2 (inhaled) had new onset/progression of BOS at 6 months after RSV (p
      > 0.99). No difference in overall survival (p = 0.41) was observed between the 2
      groups. CONCLUSIONS: This retrospective study demonstrates no significant
      differences in 6-month outcomes between oral and inhaled ribavirin therapy for
      RSV infection after lung transplantation.

PMID- 22621748
TI  - Ultrasound assisted copolymerization of acrylonitrile with N-amino phenyl
      maleimides and N-amino phenyl 2,3 dimethyl maleimides.
AB  - The N-amino phenyl maleimide (N-APhM) and N-amino phenyl 2,3 dimethyl maleimide
      (N-APhDiMeM) derivatives were prepared by the condensation of phenyl hydrazine
      with maleic anhydride and 2,3 dimethyl maleic anhydride respectively. (13)C NMR
      spectroscopy proved the formation of the symmetric amino maleimide structure and
      not the pyridazinone or aminoisomaleimides. The copolymerization of acrylonitrile
      with the (N-APhM) and (N-APhDiMeM) were prepared using ultrasound. The thermal
      behavior of the prepared copolymers, under nitrogen atmosphere, was investigated
      using thermogravimetry (TG) techniques. The dyeing of the copolymers formed has
      been studied using both conventional and ultrasonic techniques. The effect of dye
      bath pH, ultrasonic power, dyeing time and temperature were studied. Color
      strength values obtained were found to be higher using ultrasound than with
      conventional heating. The results of fastness properties of the dyed copolymers
      were also studied.

PMID- 22621747
TI  - On the epigenetics of vascular regulation and disease.
AB  - Consolidated knowledge is accumulating as to the role of epigenetic regulatory
      mechanisms in the physiology of vascular development and vascular tone as well as
      in the pathogenesis of cardiovascular disease. The modulation of gene expression
      through modification of the epigenome by structural changes of the chromatin
      architecture without alterations of the associated genomic DNA sequence is part
      of the cellular response to environmental changes. Such environmental conditions,
      which are finally being translated into adaptations of the cardiovascular system,
      also comprise pathological conditions such as atherosclerosis or myocardial
      infarction. This review summarizes recent findings on the epigenetics of vascular
      regulation and disease and presents nutritional and pharmacological approaches as
      novel epigenetic strategies in the prevention and treatment of cardiovascular
      disease.

PMID- 22621749
TI  - The effect of ultrasound irradiation on the convective heat transfer rate during
      immersion cooling of a stationary sphere.
AB  - It has been proven that ultrasound irradiation can enhance the rate of heat
      transfer processes. The objective of this work was to study the heat transfer
      phenomenon, mainly the heat exchange at the surface, as affected by ultrasound
      irradiation around a stationary copper sphere (k=386W m(-1)K(-1), C(p)=384J kg(
      1)K(-1), rho=8660kg m(-3)) during cooling. The sphere (0.01m in diameter) was
      immersed in an ethylene glycol-water mixture (-10 degrees C) in an ultrasonic
      cooling system that included a refrigerated circulator, a flow meter, an
      ultrasound generator and an ultrasonic bath. The temperature of the sphere was
      recorded using a data logger equipped with a T-type thermocouple in the center of
      the sphere. The temperature of the cooling medium was also monitored by four
      thermocouples situated at different places in the bath. The sphere was located at
      different positions (0.02, 0.04 and 0.06m) above the transducer surface of the
      bath calculated considering the center of the sphere as the center of the
      reference system and was exposed to different intensities of ultrasound (0, 120,
      190, 450, 890, 1800, 2800, 3400 and 4100W m(-2)) during cooling. The frequency of
      the ultrasound was 25kHz. It was demonstrated that ultrasound irradiation can
      increase the rate of heat transfer significantly, resulting in considerably
      shorter cooling times. Higher intensities caused higher cooling rates, and Nu
      values were increased from about 23-27 to 25-108 depending on the intensity of
      ultrasound and the position of the sphere. However, high intensities of
      ultrasound led to the generation of heat at the surface of the sphere, thus
      limiting the lowest final temperature achieved. An analytical solution was
      developed considering the heat generation and was fitted to the experimental data
      with R(2) values in the range of 0.910-0.998. Visual observations revealed that
      both cavitation and acoustic streaming were important for heat transfer
      phenomenon. Cavitation clouds at the surface of the sphere were the main cause of
      heating effect. The results showed that closer distances to the transducer
      surface showed higher cooling rates. On the other hand, despite having a bigger
      distance from the transducer, when the sphere was located close to the gas-liquid
      interface the enhancement factor of heat transfer was higher. Ultrasound
      irradiation showed promising effect for the enhancement of convective heat
      transfer rate during immersion cooling. More investigations are required to
      demonstrate the behavior of ultrasound assisted heat transfer and resolve the
      proper way of the application of ultrasound to assist the cooling and/or freezing
      processes.

PMID- 22621750
TI  - Efficacy of short-term adjunctive subantimicrobial dose doxycycline in diabetic
      patients--randomized study.
AB  - OBJECTIVE: To investigate the effectiveness of short-term adjunctive
      subantimicrobial dose doxycycline (SDD) treatment in patients with diabetes
      mellitus type 2 and chronic periodontitis (CP). METHODS: Thirty-four patients
      with CP and type 2 diabetes mellitus were included in the placebo-controlled,
      double-blind study. After scaling and root planing (SRP), patients were randomly
      assigned to two groups, receiving either SDD or placebo bid for 3 months. The
      probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP),
      approximal plaque index, glycated hemoglobin (HbA1c) level were recorded and
      gingival crevicular fluid (GCF) samples were collected at baseline and after 3
      month therapy for the estimation of matrix metalloproteinase-8 levels. RESULTS:
      Clinical attachment level, PD, and BOP improved significantly in both groups
      after therapy (P < 0.05). The statistically significant difference between the
      two groups after the therapy was observed only in PD in tooth sites with initial
      PD >= 4 mm (SRP + placebo: 3.41 +/- 0.6 mm vs SRP + SDD: 2.92 +/- 0.5 mm, P <
      0.05). GCF matrix metalloproteinase-8 levels were significantly reduced only in
      SRP + SDD group (P < 0.01). There were no changes in HbA1c levels after therapy.
      CONCLUSION: The short-term administration of SDD gives significant benefit at
      tooth sites with moderate disease (PD >= 4 mm) when compared to SRP alone in
      patients with diabetes and CP.

PMID- 22621751
TI  - Lipid metabolism in cancer.
AB  - Lipids form a diverse group of water-insoluble molecules that include
      triacylglycerides, phosphoglycerides, sterols and sphingolipids. They play
      several important roles at cellular and organismal levels. Fatty acids are the
      major building blocks for the synthesis of triacylglycerides, which are mainly
      used for energy storage. Phosphoglycerides, together with sterols and
      sphingolipids, represent the major structural components of biological membranes.
      Lipids can also have important roles in signalling, functioning as second
      messengers and as hormones. There is increasing evidence that cancer cells show
      specific alterations in different aspects of lipid metabolism. These alterations
      can affect the availability of structural lipids for the synthesis of membranes,
      the synthesis and degradation of lipids that contribute to energy homeostasis and
      the abundance of lipids with signalling functions. Changes in lipid metabolism
      can affect numerous cellular processes, including cell growth, proliferation,
      differentiation and motility. This review will examine some of the alterations in
      lipid metabolism that have been reported in cancer, at both cellular and
      organismal levels, and discuss how they contribute to different aspects of
      tumourigenesis.

PMID- 22621752
TI  - Vascular responses to radiotherapy and androgen-deprivation therapy in
      experimental prostate cancer.
AB  - BACKGROUND: Radiotherapy (RT) and androgen-deprivation therapy (ADT) are standard
      treatments for advanced prostate cancer (PC). Tumor vascularization is recognized
      as an important physiological feature likely to impact on both RT and ADT
      response, and this study therefore aimed to characterize the vascular responses
      to RT and ADT in experimental PC. METHODS: Using mice implanted with CWR22 PC
      xenografts, vascular responses to RT and ADT by castration were visualized in
      vivo by DCE MRI, before contrast-enhancement curves were analyzed both semi
      quantitatively and by pharmacokinetic modeling. Extracted image parameters were
      correlated to the results from ex vivo quantitative fluorescent
      immunohistochemical analysis (qIHC) of tumor vascularization (9 F1), perfusion
      (Hoechst 33342), and hypoxia (pimonidazole), performed on tissue sections made
      from tumors excised directly after DCE MRI. RESULTS: Compared to untreated (Ctrl)
      tumors, an improved and highly functional vascularization was detected in
      androgen-deprived (AD) tumors, reflected by increases in DCE MRI parameters and
      by increased number of vessels (VN), vessel density (VD), and vessel area
      fraction (VF) from qIHC. Although total hypoxic fractions ( HF) did not change,
      estimated acute hypoxia scores (AHS)--the proportion of hypoxia staining within
      50 MUm from perfusion staining--were increased in AD tumors compared to in Ctrl
      tumors. Five to six months after ADT renewed castration-resistant (CR) tumor
      growth appeared with an even further enhanced tumor vascularization. Compared to
      the large vascular changes induced by ADT, RT induced minor vascular changes.
      Correlating DCE MRI and qIHC parameters unveiled the semi-quantitative parameters
      area under curve (AUC) from initial time-points to strongly correlate with VD and
      VF, whereas estimation of vessel size (VS) by DCE MRI required pharmacokinetic
      modeling. HF was not correlated to any DCE MRI parameter, however, AHS may be
      estimated after pharmacokinetic modeling. Interestingly, such modeling also
      detected tumor necrosis very strongly. CONCLUSIONS: DCE MRI reliably allows non
      invasive assessment of tumors' vascular function. The findings of increased tumor
      vascularization after ADT encourage further studies into whether these changes
      are beneficial for combined RT, or if treatment with anti-angiogenic therapy may
      be a strategy to improve the therapeutic efficacy of ADT in advanced PC.

PMID- 22621753
TI  - Higher risk of matrix metalloproteinase (MMP-2, 7, 9) and tissue inhibitor of
      metalloproteinase (TIMP-2) genetic variants to gallbladder cancer.
AB  - BACKGROUND: Matrix metalloproteinase belong to family of pericellular
      collagenases which degrade extracellular matrix (ECM), and is involved in the
      modulation and susceptibility of various cancers. METHODOLOGY: The present study
      included 410 gallbladder (GBC) cases and 230 healthy controls from North India.
      Study examined the associations of polymorphisms of MMP-2c.735C>T (rs2285053),
      MMP-2c.1306 C>T (rs243865), MMP7c.181A>G (rs11568818), MMP-9p.R279Q (rs17556) MMP
      9p.P574R (rs2250889), MMP-9 p.R668Q (rs17577) and TIMP2c.418 G>C (rs8179090) to
      GBC susceptibility. Genotyping was carried out by PCR-RFLP. Statistical analysis
      was performed by using SPSS ver16. RESULTS: The MMP-2 c.735 [CT+TT], MMP-2c.1306
      [CT+TT], MMP7 c.181 [AG+GG] and MMP-9 p.668 [RQ+QQ],TIMP2c.418 [GG+GC] genotypes
      were significantly associated with increased risk of GBC (P = 0.01; [OR]1.87, P =
      0.02; [OR] 1.68, P = 0.02; [OR]=1.61, P = 0.002; [OR]=1.91,P = 0.01; [OR]=1.78
      and (P = 0.03; [OR]=1.68; P = 0.01; [OR]=1.78 respectively). Haplotypes [C(-735) 
      T(-1306) ] and [T(-1306) -C(-735) ] of MMP-2 (P = <0.005; [OR] =1.78 P = <0.0001;
      [OR] =2.09) and haplotype [Q(279) -P(574) -Q(668) ]of the MMP-9 (P = 0.04; [OR]
      =2.75) were significantly associated with GBC risk. On stratification of GBC
      patients with/without gallstones, MMP-2 haplotypes were associated with higher
      GBC risk in patients accompanying gallstones whereas MMP-9 haplotypes showed risk
      in patients without stones. Combined effect of > 3 MMP/TIMP variant containing
      genotypes imparted increased risk of GBC (P < 0.0001; [OR] =3.36). Multivariate
      logistic regression results also supported association of MMP-2 (c.735C>T, c.1306
      C>T), MMP-9 p.R668Q and TIMP2c.418G>C variants with GBC susceptibility.
      CONCLUSION: This study suggests that genetic variants in MMP-2,7,9 and TIMP
      2genes are associated with higher susceptibility of gallbladder cancer.

PMID- 22621754
TI  - Development and validation of a predictive equation for lean body mass in
      children and adolescents.
AB  - BACKGROUND: Lean body mass (LBM) is not easy to measure directly in the field or
      clinical setting. Equations to predict LBM from simple anthropometric measures,
      which account for the differing contributions of fat and lean to body weight at
      different ages and levels of adiposity, would be useful to both human biologists
      and clinicians. AIM: To develop and validate equations to predict LBM in children
      and adolescents across the entire range of the adiposity spectrum. SUBJECTS AND
      METHODS: Dual energy X-ray absorptiometry was used to measure LBM in 836 healthy
      children (437 females) and linear regression was used to develop sex-specific
      equations to estimate LBM from height, weight, age, body mass index (BMI) for age
      z-score and population ancestry. Equations were validated using bootstrapping
      methods and in a local independent sample of 332 children and in national data
      collected by NHANES. RESULTS: The mean difference between measured and predicted
      LBM was - 0.12% (95% limits of agreement - 11.3% to 8.5%) for males and - 0.14% (
      - 11.9% to 10.9%) for females. Equations performed equally well across the entire
      adiposity spectrum, as estimated by BMI z-score. Validation indicated no over
      fitting. LBM was predicted within 5% of measured LBM in the validation sample.
      CONCLUSION: The equations estimate LBM accurately from simple anthropometric
      measures.

PMID- 22621755
TI  - Implementation of the simplified stochastic model of ageing for longitudinal
      osteoarthritis data assessment.
AB  - BACKGROUND: Occurrence and progression of age-related irreversible degradations
      of skeletal joints, osteoarthritis (OA), has a stochastic nature. However, it is
      commonly described using polynomial models, which may not necessarily be optimal.
      AIM: To implement a stochastic model of gradual accumulation of the distinct
      changes for estimating individuals' putative age at onset and risk of the process
      advancing in the OA longitudinal data. SUBJECTS AND METHODS: The model was
      formulated as a discrete Markov process. It was applied to radiographic knee
      osteoarthritis (RKOA) data: 243 Kellgren-Lawrence (K/L) and 207 osteophytes (OP)
      score histories from the 15-year follow-up Chingford study. RESULTS: The model
      performance was examined in Monte-Carlo simulations. The mean age at onset of
      knee osteoarthritis was: 53.04 and 53.23 years and the average annual risk of one
      K/L and one OP grade appearance was: 0.066 and 0.025, respectively. The analysis
      also suggested that there is 3-4 years difference between the inferred age at
      onset and the age when knee osteoarthritis becomes detectable on radiograph.
      CONCLUSION: The stochastic model provides more accurate description of the
      empiric data compared with the corresponding polynomial model. The model-based
      individual's estimates could be used as an important tool to fit age-related
      patterns of the corresponding diseases and conditions.

PMID- 22621756
TI  - Effect of the type of population on estimates of mean body mass index and
      prevalence of overweight and obesity: a systematic review of studies of
      Portuguese adults.
AB  - BACKGROUND: Prevalence estimates for overweight/obesity vary widely between
      studies, reflecting true differences across settings and biased sampling. AIM: To
      compare mean body mass index (BMI) and prevalences of overweight/obesity in
      samples of different types of population, in Portugal. METHODS: A systematic
      review was conducted to identify studies that assessed the distribution of BMI
      and overweight/obesity in different populations (general population, blood
      donors, university students, occupational groups, healthcare users and
      volunteers). Linear regression was used to quantify age-, sex- and survey year
      adjusted differences in these outcomes. RESULTS: When weight/height were
      measured, BMI was higher among blood donors (+1.4 kg/m(2)) and lower in
      occupational groups ( - 0.9 kg/m(2)), compared to the general population.
      Overweight prevalence was lower among university students ( - 5.2%). Obesity
      prevalence was higher among occupational groups (+4.5%) and healthcare users
      (+8.9%); and lower in volunteers ( - 6.4%). With self-reported data, BMI was
      lower among university students ( - 0.9 kg/m(2)), occupational groups ( - 1.2
      kg/m(2)) and volunteers ( - 0.7 kg/m(2)). Healthcare users had higher overweight
      (+6.7%) and lower obesity prevalences ( - 4.3%) and occupational groups lower
      obesity prevalence ( - 5.7%). CONCLUSION: Estimates varied largely across
      population types. Commonly used solutions for an easier assembling of study
      samples are likely to yield biased estimates of the distributions in the general
      population.

PMID- 22621757
TI  - Natural selection among coastal populations of India: trend and extent.
AB  - BACKGROUND: Coastal populations have always been exposed to socio-cultural and
      natural vulnerability. The correlates between these coastal populations and their
      selection potentials have not been previously described. AIM: To describe
      selection potentials, their trend and extent among coastal and non-coastal
      populations of the Indian continent. SUBJECTS AND METHODS: Data on fertility and
      mortality differentials among five coastal populations were collected from 448
      women of Orissa and Goa. Selection potential was computed. In addition, 48
      studies among 100 different populations of India were reviewed for similar
      parameters, for comparison. RESULTS: Total index of selection (I(t)) varied from
      0.221-0.417 in the population of Orissa; whereas the population of Goa showed a
      moderate index of selection. Regression analysis showed that among the coastal
      population the contribution of index of mortality (I(m)) is higher (92.5%) in
      total selection index (I(t)) as compared to non-coastal populations (56.4%).
      After 1991, there was a radical shift in the role of mortality in the entire
      region. Simultaneously, the selection intensity (I(t)) has gradually declined.
      CONCLUSION: There is a significant difference in the extent and process of
      natural selection among coastal and non-coastal populations. Mortality is playing
      a greater role in the total selection intensity of coastal populations, although
      the trend is declining in the entire region and reversal in the roles of I(m) and
      index of fertility (I(f)) is witnessed.

PMID- 22621758
TI  - Prevalent trends in relatively high blood pressure among children and adolescents
      in Shandong, China.
AB  - BACKGROUND: Hypertension in adults remains a major public health problem. Several
      studies have provided ample evidence that hypertension in adults has its onset in
      childhood; children and adolescents with elevated blood pressure (BP) are more
      likely to become hypertensive adults. AIM: The present study examined the
      prevalent trend in relatively high BP among children and adolescents during the
      past 10 years in Shandong, China. SUBJECTS AND METHODS: Data for this study were
      obtained from three national surveys on students' constitution and health carried
      out by the government in 2000, 2005 and 2010 in Shandong Province, China. A total
      of 22 548 students aged 7-17 years old were included in this study (7776 in 2000,
      7878 in 2005 and 6894 in 2010). Height, weight and BP of all subjects were
      measured. Relatively high BP status was defined as systolic blood pressure (SBP)
      and/or diastolic blood pressure (DBP) >= 95th percentile for age and gender. Body
      mass index (BMI) of adolescents was calculated from their height and weight and
      prevalence of overweight and obesity were obtained according to the screening
      criteria for overweight and obesity in Chinese students using BMI. RESULTS: In
      the past 10 years, the prevalence of relatively high BP increased. The overall
      prevalence of relatively high BP of children and adolescents aged 7-17 increased
      from 19.29% (boys) and 14.69% (girls) in 2000 to 26.16% (boys) and 19.77% (girls)
      in 2010, respectively. The prevalence of combined overweight and obesity
      increased from 22.26% (boys) and 12.23% (girls) in 2000 to 33.81% (boys) and
      19.48% (girls) in 2010. CONCLUSION: The prevalence of relatively high BP among
      children and adolescents increased dramatically from 2000 to 2010 in Shandong,
      China. It has become a public health problem and comprehensive interference
      measures are urgently needed.

PMID- 22621759
TI  - Challenges in clinical genomics.
AB  - A report on the Genomic Disorders 2012: Genomics of Rare Diseases meeting,
      Hinxton, UK, 21-23 March 2012.

PMID- 22621760
TI  - High insoluble fibre content increases in vitro starch digestibility in partially
      baked breads.
AB  - Wheat breads prepared from frozen partially baked breads were characterized by
      their content of rapidly digestible starch (RDS) and slowly digestible starch
      (SDS) by the in vitro starch digestibility method developed by Englyst. Breads
      with different contents and types of fibre and breads prepared with different
      fermentation processes were studied. Bread with inulin and with a double
      fermentation had the lowest RDS content of 58.8 +/- 1.7 and 60.0 +/- 1.9 (% dry
      matter), respectively. Wheat bran bread, seeded bread, triple fermentation white
      bread and baguette-type bread showed values of RDS between 63.1 +/- 1.7 and 65.7
      +/- 1.7 with no significant differences between them (p < 0.05). The fraction of
      SDS was higher in wheat breads than in breads with added fibre. The highest
      values of the starch digestive rate index (SDRI) were obtained by the three types
      of breads with added fibre, which ranged from 91.8 +/- 3.5 to 95.8 +/- 3.5 versus
      80.2 +/- 3.5 to 87.5 +/- 3.5 for white wheat breads. A significant (p < 0.01)
      positive linear correlation between the insoluble fibre content and SDRI was
      obtained (R2 = 0.96). Insoluble fibre dilutes and disrupts gluten network and
      probably weakens the interaction between gluten and starch, which protects starch
      from digestive enzymes action. Scanning electronic microscopy microstructure of
      bread crumbs corroborated this statement.

PMID- 22621762
TI  - On the modularity of implicit sequence learning: independent acquisition of
      spatial, symbolic, and manual sequences.
AB  - Learning sequential structures is of fundamental importance for a wide variety of
      human skills. While it has long been debated whether implicit sequence learning
      is perceptual or response-based, here we propose an alternative framework that
      cuts across this dichotomy and assumes that sequence learning rests on
      associative changes that can occur concurrently in distinct processing systems
      and support the parallel acquisition of multiple uncorrelated sequences. In three
      experiments we used a serial search task to test critical predictions of this
      framework. Experiments 1 and 2 showed that participants learnt uncorrelated
      sequences of auditory letters and manual responses, as well as sequences of
      visual letters, spatial locations, and manual responses simultaneously, as
      indicated by a reliable response time (RT) cost incurred by occasional deviants
      violating either of the sequences. This RT cost was reliable even when
      participants showing explicit knowledge were excluded. In Experiment 3 learning
      of spatial and nonspatial sequences was functionally dissociated: whereas a
      spatio-motor distractor task disrupted learning of location but not of letter
      sequences, a phonological distractor task had the reverse effect. The distractor
      tasks thus did not reduce unspecific attentional resources, but selectively
      disrupted the formation of sequential associations within spatial and nonspatial
      processing dimensions. These results support the view that implicit sequence
      learning rests on experience-dependent changes that can occur in parallel in
      multiple processing systems involved in spatial attention, object recognition,
      phonological processing, and manual response selection. The resulting dimension
      specific sequence representations support independent predictions of what will
      appear next, where it will appear, and how one will have to respond to it.

PMID- 22621761
TI  - Increased myocardial SERCA expression in early type 2 diabetes mellitus is
      insulin dependent: In vivo and in vitro data.
AB  - BACKGROUND: Calcium (Ca2+) handling proteins are known to play a pivotal role in
      the pathophysiology of cardiomyopathy. However little is known about early
      changes in the diabetic heart and the impact of insulin treatment (Ins). METHODS:
      Zucker Diabetic Fatty rats treated with or without insulin (ZDF +/- Ins, n = 13)
      and lean littermates (controls, n = 7) were sacrificed at the age of 19 weeks.
      ZDF + Ins (n = 6) were treated with insulin for the last 6 weeks of life. Gene
      expression of Ca2+ ATPase in the cardiac sarcoplasmatic reticulum (SERCA2a,
      further abbreviated as SERCA) and phospholamban (PLB) were determined by northern
      blotting. Ca2+ transport of the sarcoplasmatic reticulum (SR) was assessed by
      oxalate-facilitated 45Ca-uptake in left ventricular homogenates. In addition,
      isolated neonatal cardiomyocytes were stimulated in cell culture with insulin,
      glucose or triiodthyronine (T3, positive control). mRNA expression of SERCA and
      PLB were measured by Taqman PCR. Furthermore, effects of insulin treatment on
      force of contraction and relaxation were evaluated by cardiomyocytes grown in a
      three-dimensional collagen matrix (engineered heart tissue, EHT) stimulated for 5
      days by insulin. By western blot phosphorylations status of Akt was determed and
      the influence of wortmannin. RESULTS: SERCA levels increased in both ZDF and ZDF
      + Ins compared to control (control 100 +/- 6.2 vs. ZDF 152 +/- 26.6* vs. ZDF +
      Ins 212 +/- 18.5*# % of control, *p < 0.05 vs. control, #p < 0.05 vs. ZDF)
      whereas PLB was significantly decreased in ZDF and ZDF + Ins (control 100 +/- 2.8
      vs. ZDF 76.3 +/- 13.5* vs. ZDF + Ins 79.4 +/- 12.9* % of control, *p < 0.05 vs
      control). The increase in the SERCA/PLB ratio in ZDF and ZDF +/- Ins was
      accompanied by enhanced Ca2+ uptake to the SR (control 1.58 +/- 0.1 vs. ZDF 1.85
      +/- 0.06* vs. ZDF + Ins 2.03 +/- 0.1* MUg/mg/min, *p < 0.05 vs. control).
      Interestingly, there was a significant correlation between Ca2+ uptake and
      SERCA2a expression. As shown by in-vitro experiments, the effect of insulin on
      SERCA2a mRNA expression seemed to have a direct effect on cardiomyocytes.
      Furthermore, long-term treatment of engineered heart tissue with insulin
      increased the SERCA/PLB ratio and accelerated relaxation time. Akt was
      significantly phosphorylated by insulin. This effect could be abolished by
      wortmannin. CONCLUSION: The current data demonstrate that early type 2 diabetes
      is associated with an increase in the SERCA/PLB ratio and that insulin directly
      stimulates SERCA expression and relaxation velocity. These results underline the
      important role of insulin and calcium handling proteins in the cardiac adaptation
      process of type 2 diabetes mellitus contributing to cardiac remodeling and show
      the important role of PI3-kinase-Akt-SERCA2a signaling cascade.

PMID- 22621763
TI  - The Ontology for Parasite Lifecycle (OPL): towards a consistent vocabulary of
      lifecycle stages in parasitic organisms.
AB  - BACKGROUND: Genome sequencing of many eukaryotic pathogens and the volume of data
      available on public resources have created a clear requirement for a consistent
      vocabulary to describe the range of developmental forms of parasites. Consistent
      labeling of experimental data and external data, in databases and the literature,
      is essential for integration, cross database comparison, and knowledge discovery.
      The primary objective of this work was to develop a dynamic and controlled
      vocabulary that can be used for various parasites. The paper describes the
      Ontology for Parasite Lifecycle (OPL) and discusses its application in parasite
      research. RESULTS: The OPL is based on the Basic Formal Ontology (BFO) and
      follows the rules set by the OBO Foundry consortium. The first version of the OPL
      models complex life cycle stage details of a range of parasites, such as
      Trypanosoma sp., Leishmaniasp., Plasmodium sp., and Shicstosoma sp. In addition,
      the ontology also models necessary contextual details, such as host information,
      vector information, and anatomical locations. OPL is primarily designed to serve
      as a reference ontology for parasite life cycle stages that can be used for
      database annotation purposes and in the lab for data integration or information
      retrieval as exemplified in the application section below. CONCLUSION: OPL is
      freely available at http://purl.obolibrary.org/obo/opl.owl and has been submitted
      to the BioPortal site of NCBO and to the OBO Foundry. We believe that database
      and phenotype annotations using OPL will help run fundamental queries on
      databases to know more about gene functions and to find intervention targets for
      various parasites. The OPL is under continuous development and new parasites
      and/or terms are being added.

PMID- 22621764
TI  - Acute gastrointestinal and genitourinary toxicity of image-guided intensity
      modulated radiation therapy for prostate cancer using a daily water-filled
      endorectal balloon.
AB  - BACKGROUND: Our purpose was to report acute gastrointestinal (GI) and
      genitourinary (GU) toxicity rates for prostate cancer patients undergoing image
      guided intensity modulated radiation therapy (IG-IMRT) with a daily endorectal
      water-filled balloon (ERBH2O), and assess associations with planning parameters
      and pretreatment clinical characteristics. METHODS: The first 100 patients
      undergoing prostate and proximal seminal vesicle IG-IMRT with indexed-lumen 100
      cc ERBH2O to 79.2 Gy in 1.8 Gy fractions at our institution from 12/2008- 12/2010
      were assessed. Pretreatment characteristics, organ-at-risk dose volume
      histograms, and maximum GU and GI toxicities (CTCAE 3.0) were evaluated. Logistic
      regression models evaluated univariate association between toxicities and
      dosimetric parameters, and uni- and multivariate association between toxicities
      and pretreatment characteristics. RESULTS: Mean age was 68 (range 51-88). Thirty
      two, 49, and 19 patients were low, intermediate, and high-risk, respectively; 40
      received concurrent androgen deprivation. No grade 3 or greater toxicities were
      recorded. Maximum GI toxicity was grade 0, 1, and 2 in 69%, 23%, and 8%,
      respectively. Infield (defined as 1 cm above/below the CTV) rectal mean/median
      doses, D75, V30, and V40 and hemorrhoid history were associated with grade 2 GI
      toxicity (Ps < 0.05). Maximum acute GU toxicity was grade 0, 1, and 2 for 17%,
      41%, and 42% of patients, respectively. Infield bladder V20 (P = 0.03) and
      pretreatment International Prostate Symptom Scale (IPSS) (P = 0.003) were
      associated with grade 2 GU toxicity. CONCLUSION: Prostate IG-IMRT using a daily
      ERBH2O shows low rates of acute GI toxicity compared to previous reports of air
      filled ERB IMRT when using stringent infield rectum constraints and comparable GU
      toxicities.

PMID- 22621765
TI  - Distinct biological activities of C3 and ADP-ribosyltransferase-deficient C3
      E174Q.
AB  - Low-molecular-weight GTP-binding proteins of the Rho family control the
      organization of the actin cytoskeleton in eukaryotic cells. Dramatic
      reorganization of the actin cytoskeleton is caused by the C3 exoenzyme derived
      from Clostridium botulinum (C3), based on ADP-ribosylation of RhoA/B/C. In
      addition, wild-type as well as ADP-ribosyltransferase-deficient C3-E174Q induce
      axonal outgrowth of primary murine hippocampal neurons and prevent growth cone
      collapse, indicating a non-enzymatic mode of action. In this study, we compared
      the effects of C3-E174Q and wild-type C3 in the murine hippocampal cell line
      HT22. Treatment of HT22 cells with C3 resulted in Rho ADP-ribosylation and cell
      rounding. The ADP-ribosyltransferase-deficient mutant C3-E174Q did not induce
      either Rho ADP-ribosylation or morphological changes. C3 as well as C3-E174Q
      treatment resulted in growth arrest, reduced expression of cyclin D levels, and
      increased expression of RhoB, a negative regulator of cell-cycle progression.
      Serum starvation induced apoptosis in HT22 cells, as determined on the basis of
      increased expression of caspase-9 and Bax. C3 but not C3-E174Q protected serum
      starved HT22 cells from apoptosis. This is the first study separating ADP
      ribosyltransferase-dependent from ADP-ribosyltransferase-independent effects of
      C3. While morphological changes and anti-apoptotic activity strictly depend on
      ADP-ribosyltransferase activity, the anti-proliferative effects are independent
      of ADP-ribosyltransferase activity.

PMID- 22621766
TI  - UVSSA and USP7: new players regulating transcription-coupled nucleotide excision
      repair in human cells.
AB  - Transcription-coupled nucleotide excision repair (TC-NER) specifically removes
      DNA damage located in actively transcribed genes. Defects in TC-NER are
      associated with several human disorders, including Cockayne syndrome (CS) and
      ultraviolet (UV)-sensitive syndrome (UVSS). Using exome sequencing, and genetic
      and proteomic approaches, three recent studies have identified mutations in the
      UVSSA gene as being responsible for UVSS-A. These findings suggest a new
      mechanistic model involving UV-stimulated scaffold protein A (UVSSA) and the
      ubiquitin-specific protease 7 (USP7) in the fate of stalled RNA polymerase II
      during TC-NER, and provide insights into the diverse clinical features of CS and
      UVSS.

PMID- 22621767
TI  - Aboriginal health workers experience multilevel barriers to quitting smoking: a
      qualitative study.
AB  - INTRODUCTION: Long-term measures to reduce tobacco consumption in Australia have
      had differential effects in the population. The prevalence of smoking in
      Aboriginal peoples is currently more than double that of the non-Aboriginal
      population. Aboriginal Health Workers are responsible for providing primary
      health care to Aboriginal clients including smoking cessation programs. However,
      Aboriginal Health Workers are frequently smokers themselves, and their smoking
      undermines the smoking cessation services they deliver to Aboriginal clients. An
      understanding of the barriers to quitting smoking experienced by Aboriginal
      Health Workers is needed to design culturally relevant smoking cessation
      programs. Once smoking is reduced in Aboriginal Health Workers, they may then be
      able to support Aboriginal clients to quit smoking. METHODS: We undertook a
      fundamental qualitative description study underpinned by social ecological
      theory. The research was participatory, and academic researchers worked in
      partnership with personnel from the local Aboriginal health council. The barriers
      Aboriginal Health Workers experience in relation to quitting smoking were
      explored in 34 semi-structured interviews (with 23 Aboriginal Health Workers and
      11 other health staff) and 3 focus groups (n = 17 participants) with key
      informants. Content analysis was performed on transcribed text and interview
      notes. RESULTS: Aboriginal Health Workers spoke of burdensome stress and grief
      which made them unable to prioritise quitting smoking. They lacked knowledge
      about quitting and access to culturally relevant quitting resources.
      Interpersonal obstacles included a social pressure to smoke, social exclusion
      when quitting, and few role models. In many workplaces, smoking was part of
      organisational culture and there were challenges to implementation of Smokefree
      policy. Respondents identified inadequate funding of tobacco programs and a lack
      of Smokefree public spaces as policy level barriers. The normalisation of smoking
      in Aboriginal society was an overarching challenge to quitting. CONCLUSIONS:
      Aboriginal Health Workers experience multilevel barriers to quitting smoking that
      include personal, social, cultural and environmental factors. Multidimensional
      smoking cessation programs are needed that reduce the stress and burden for
      Aboriginal Health Workers; provide access to culturally relevant quitting
      resources; and address the prevailing normalisation of smoking in the family,
      workplace and community.

PMID- 22621768
TI  - Wnt signaling and forebrain development.
AB  - Components of the Wnt signaling pathway are expressed in a tightly regulated and
      spatially specific manner during development of the forebrain, and Wnts are key
      regulators of regional forebrain identity. Wnt signaling from the cortical hem
      regulates the expansion and cell-type specification of the adjacent
      neuroepithelium and, in conjunction with Bmp, Fgf, and Shh signaling, controls
      dorsal-ventral forebrain patterning. Subsequently, Wnt signaling dynamically
      regulates the behavior of cortical progenitor cells, initially promoting the
      expansion of radial glia progenitor cells and later inducing neurogenesis by
      promoting terminal differentiation of intermediate progenitor cells. A role for
      Wnt signaling in cell-type specification has also been proposed.

PMID- 22621769
TI  - Optimization of soy isoflavone extraction with different solvents using the
      simplex-centroid mixture design.
AB  - The objective of this study was to optimize the extraction of different
      isoflavone forms (glycosidic, malonyl-glycosidic, aglycone and total) from
      defatted cotyledon soy flour using the simplex-centroid experimental design with
      four solvents of varying polarity (water, acetone, ethanol and acetonitrile). The
      obtained extracts were then analysed by high-performance liquid chromatography.
      The profile of the different soy isoflavones forms varied with different
      extractions solvents. Varying the solvent or mixture used, the extraction of
      different isoflavones was optimized using the centroid-simplex mixture design.
      The special cubic model best fitted to the four solvents and its combination for
      soy isoflavones extraction. For glycosidic isoflavones extraction, the polar
      ternary mixture (water, acetone and acetonitrile) achieved the best extraction;
      malonyl-glycosidic forms were better extracted with mixtures of water, acetone
      and ethanol. Aglycone isoflavones, water and acetone mixture were best extracted
      and total isoflavones, the best solvents were ternary mixture of water, acetone
      and ethanol.

PMID- 22621770
TI  - Kruppel-like zinc finger proteins in end-stage COPD lungs with and without severe
      alpha1-antitrypsin deficiency.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is influenced by
      environmental and genetic factors. An important fraction of COPD cases harbor a
      major genetic determinant, inherited ZZ (Glu342Lys) alpha1-antitrypsin deficiency
      (AATD). A study was undertaken to investigate gene expression patterns in end
      stage COPD lungs from patients with and without AATD. METHODS: Explanted lungs of
      end-stage ZZ AATD-related (treated and non-treated with AAT augmentation therapy)
      and "normal" MM COPD, and liver biopsies from patients suffering from liver
      cirrhosis with and without ZZ AATD were used for gene expression analysis by
      Affymetrix microarrays or RT-PCR. RESULTS: A total of 162 genes were found to be
      differentially expressed (p-value <= 0.05 and |FC| >= 2) between MM and ZZ COPD
      patients. Of those, 134 gene sets were up-regulated and 28 were down-regulated in
      ZZ relative to MM lung tissue. A subgroup of genes, zinc finger protein 165,
      snail homolog 1 (Drosophila) (SNAI1), and Kruppel-like transcription factors
      (KLFs) 4 (gut), 9 and 10, perfectly segregated ZZ and MM COPD patients. The
      higher expression of KLF 9 and KLF10 has been verified in the replication cohort
      with AATD-related end-stage lung emphysema and liver cirrhosis. Furthermore,
      higher expression of KLF9, SNAI1 and DEFA1 was found in ZZ COPD lungs without
      augmentation therapy relative to MM COPD or ZZ COPD with augmentation therapy.
      CONCLUSIONS: These results reveal the involvement of transcriptional regulators
      of the zinc-finger family in COPD pathogenesis and provide deeper insight into
      the pathophysiological mechanisms of COPD with and without AATD.

PMID- 22621771
TI  - Wound healing by topical application of antioxidant iron chelators: kojic acid
      and deferiprone.
AB  - Kojic acid and deferiprone are iron chelators used for skin lightening and iron
      overload treatment, respectively. As iron chelation and free radical scavenging
      are principal factors for wound healing, it was hypothesised that the local
      application of these compounds might accelerate wound healing in rats. Ointments
      of 3%, 6% and 9% of deferiprone and kojic acid were prepared and topical
      treatment was performed on in vivo wound models for 12 days twice in day for test
      and control groups. Topical treatment with 3%, 6% and 9% showed significant
      improvement in wound healing after 4 days (P < 0.001). Topical application of 3%
      and 6% deferiprone enhanced wound healing after 8 days (P < 0.026 and P < 0.001,
      respectively). Accelerated wound healing was seen using 3% and 6% deferiprone
      after 12 days (P = 0.003 and P < 0.001, respectively). DPPH scavenging assay was
      also performed to compare the antioxidant potencies of kojic acid and
      deferiprone. Deferiprone had more free radical scavenging power than kojic acid.
      Generally, deferiprone topical treatment, accelerated wound healing more than
      kojic acid because of its higher antioxidant and iron chelation abilities.

PMID- 22621772
TI  - Proteins differentially expressed in elicited cell suspension culture of
      Podophyllum hexandrum with enhanced podophyllotoxin content.
AB  - BACKGROUND: Podophyllotoxin (PTOX), the precursor for semi-synthesis of cancer
      therapeutics like etoposide, teniposide and etophos, is primarily obtained from
      an endangered medicinal herb, Podophyllum hexandrum Royle. PTOX, a lignan is
      biosynthetically derived from the phenylpropanoid pathway. The aim of this study
      is to investigate changes in the P. hexandrum cell proteome potentially related
      to PTOX accumulation in response to methyl jasmonate (MeJA) elicitation. High
      resolution two-dimensional gel electrophoresis (2-DE) followed by colloidal
      Coomassie staining and mass spectrometric analysis was used to detect
      statistically significant changes in cell's proteome. RESULT: The HPLC analysis
      showed approximately 7-8 fold change in accumulation of PTOX, in the 12day old
      cell suspension culture (i.e. after 9days of elicitation) elicited with 100 MUM
      MeJA as compared to the control. Using 2-DE a total of 233 spots was detected,
      out of which 105 spots were identified by MALDI TOF-TOF MS/MS. Data were
      subjected to functional annotation from a biological point of view through KEGG.
      The phenylpropanoid and monolignol pathway enzymes were identified, amongst
      these, chalcone synthase, polyphenol oxidase, caffeoyl CoA 3-O-methyltransferase,
      S-adenosyl-L-methionine-dependent methyltransferases, caffeic acid-O-methyl
      transferase etc. are noted as important. The relation of other differentially
      accumulated proteins with varied effects caused by elicitors on P. hexandrum
      cells namely stress and defense related protein, transcription and DNA
      replication and signaling are also discussed. CONCLUSIONS: Elicitor-induced PTOX
      accumulation in P. hexandrum cell cultures provides a responsive model system to
      profile modulations in proteins related to phenylpropanoid/monolignol
      biosynthesis and other defense responses. Present findings form a baseline for
      future investigation on a non-sequenced medicinal herb P. hexandrum at molecular
      level.

PMID- 22621773
TI  - Prophylactic treatment with flumethrin, a pyrethroid (Bayticol((r)), Bayer),
      against Anaplasma phagocytophilum infection in lambs.
AB  - BACKGROUND: [corrected] Anaplasma phagocytophilum (formerly Ehrlichia
      phagocytophila) causes the disease tick-borne fever (TBF) in domestic ruminants
      and has for decades been one of the main scourges for the sheep industry in the
      coastal areas of Norway. Current control strategies are based on reduction of
      tick infestation by chemical acaricides. METHODS: In the present study, we
      investigated if frequent pour-on applications of pyrethroids would reduce tick
      infestion rate and seroprevalence of A. phagocytophilum infection in sheep. Forty
      lambs, one month old, of the Norwegian White Sheep breed were used. The lambs
      belonged to the experimental sheep flock at the Department of Production Animal
      Clinical Sciences. None of the lambs had been on I. ricinus infested pasture
      before turnout (day 0). All lambs were twins and twenty lambs were treated with a
      pour-on pyrethroid (Bayticol((r)), Bayer A/S, DK-2300) with a dose of 5 ml on
      days 0, 14, 28, 42, 56, 70, 84, 98, 112 and 128. Twenty lambs were untreated
      controls. The lambs were collected every fourteen days on pasture for treatment.
      In addition, the lambs were examined for ticks, blood sampled, weighed, and
      rectal temperature was recorded. RESULTS AND CONCLUSION: A significant reduction
      in tick infestion rate was detected on treated lambs. However, the present
      results indicate that frequent acaricide treatment does not reduce the
      seroprevalence to A. phagocytophilum on tick-infested pasture.

PMID- 22621774
TI  - Combined use of super-oxidised solution with negative pressure for the treatment
      of pressure ulcers: case report.
AB  - A 61-year-old patient was affected by flaccid paraplegia for 20 years because of
      post-traumatic medullar injury caused by an accidental fall, with stage IV sacral
      pressure ulcer for 3 years. The patient later developed stage IV sacral pressure
      ulcer. After 6 months, a new granulation tissue formation appeared in the wound
      and a reduction of its diameter was observed (length 20 cm, width 15 cm, depth 5
      cm). We therefore treated the wound with PRP (platelet rich plasma) intra-lesion
      and peri-lesional injections. The wounds were covered with three-dimensional
      polymerised hyaluronic acid medicated biologic dressing. After the surgery, a
      moderate reduction in diameter and the depth was observed. Super-oxidised
      solution (SOS-Dermacyn) was applied to control infection locally together with
      negative pressure to control the exudate and the local bacteremia, to avoid
      infectious complications without application of systematic antibiotic therapy.

PMID- 22621775
TI  - Electrolytic reduction of abscisic acid methyl ester and its free acid.
AB  - Abscisic acid (ABA, 1), a plant hormone, has electrophilicity derived almost
      entirely from the side-chain, 3-methylpenta-2,4-dienoic acid. The electrochemical
      property of ABA was investigated by analysis of its cathodic reaction. ABA methyl
      ester (1-Me) was reduced at a peak potential of -1.6 V to give a unique and
      unstable bicyclic compound (5-Me) as a major product at pH 3 and 7. This finding
      showed that an electron was absorbed in the conjugated dienecarboxyl group, and
      that C-5 with a high electron density attacked C-2' through an intramolecular
      nucleophilic addition. At pH 10, in addition to 5-Me, a compound 4-Me was formed
      by isomerization of 5-Me under alkaline conditions. For a cathodic reaction of
      ABA at pH 3 and 7, compound 5 was a major product as well as in the case of ABA
      methyl ester. However, at pH 10, a dimer (6) with an epoxy group, 1'-deoxy-ABA
      (7) and other compounds were formed instead of compounds 4 and 5. Compounds 4 and
      5 were biologically inactive, suggesting the importance of the electrophilic side
      chain of ABA for biological activity.

PMID- 22621776
TI  - Pharmacokinetic profile of beclomethasone dipropionate hydrofluoroalkane after
      intranasal administration versus oral inhalation in healthy subjects: results of
      a single-dose, randomized, open-label, 3-period crossover study.
AB  - BACKGROUND: Beclomethasone dipropionate (BDP) is an anti-inflammatory
      corticosteroid that is rapidly metabolized to the pharmacologically active
      monoester, beclomethasone-17-monopropionate (17-BMP). Recently, a
      hydrofluoroalkane (HFA)-propelled nasal aerosol formulation of BDP was developed
      to treat allergic rhinitis. However, the pharmacokinetic profile of BDP HFA nasal
      aerosol has not been previously investigated. OBJECTIVE: This study evaluated and
      compared the systemic levels of 17-BMP and BDP after a single dose of
      intranasally administered or orally inhaled BDP HFA in healthy subjects. METHODS:
      In this single-center, randomized, open-label, 3-period crossover study, healthy
      subjects received single doses of intranasal BDP HFA (80 and 320 MUg) and orally
      inhaled BDP HFA (320 MUg). The primary pharmacokinetic parameters assessed were
      area under the concentration-time curve until the last measurable value
      (AUC(last)) and C(max) for 17-BMP. For AUC(last) and C(max), point estimates for
      treatment differences and CIs were calculated on the log scale and then
      exponentiated to provide estimates of the geometric mean ratios (GMRs) and
      associated CIs. RESULTS: Thirty subjects were randomized to receive study
      medication (aged 18-45 years, 66.7% male). Mean plasma concentrations of 17-BMP
      after intranasal administration of BDP HFA (for both 80- and 320-MUg doses) were
      substantially lower than that of orally inhaled BDP HFA (320 MUg) across all time
      points. Mean AUC(last) values of 17-BMP for intranasal 80 MUg, intranasal 320
      MUg, and orally inhaled 320 MUg were 295.8, 1139.7, and 4140.3 pg.hr/mL,
      respectively. Mean C(max) values were 92.1, 262.7, and 1343.7 pg/mL,
      respectively. The GMR of AUC(last) for 17-BMP with intranasal BDP HFA 320 MUg
      versus orally inhaled BDP HFA 320 MUg was 0.275, indicating substantially lower
      systemic bioavailability with intranasal administration than with oral
      inhalation. Similarly, the GMR of AUC(last) for 17-BMP with intranasal BDP HFA 80
      MUg versus 320 MUg was 0.260, suggesting approximate dose proportionality (4-fold
      difference). Pharmacokinetic results for BDP were similar to those seen for 17
      BMP. All doses of intranasal and orally inhaled BDP HFA were well tolerated, and
      no treatment-related adverse events were reported. CONCLUSIONS: The results of
      this study suggest that 80 and 320 MUg BDP HFA nasal aerosols have substantially
      lower systemic bioavailability than 320 MUg orally inhaled BDP HFA in healthy
      subjects. All treatments were well tolerated. ClinicalTrials.gov identifier:
      NCT01537692.

PMID- 22621778
TI  - The usefulness of the revised classification for chronic kidney disease by the
      KDIGO for determining the frequency of diabetic micro- and macroangiopathies in
      Japanese patients with type 2 diabetes mellitus.
AB  - AIMS: A new classification of chronic kidney disease (CKD) was proposed by the
      Kidney Disease: Improving Global Outcomes (KDIGO) in 2011. The major point of
      revision of this classification was the introduction of a two-dimensional staging
      of the CKD according to the level of albuminuria in addition to the GFR level.
      Furthermore, the previous CKD stage 3 was subdivided into two stages (G3a and
      G3b). We examined the prevalence of diabetic micro- and macroangiopathies in
      patients with type 2 diabetes mellitus based on the new classification. METHODS:
      A cross-sectional study was performed in 2018 patients with type 2 diabetes
      mellitus. RESULTS: All of the diabetic micro- and macroangiopathies significantly
      more common in the later stages of both the GFR and albuminuria. The proportion
      of subjects with diabetic retinopathy, neuropathy, cerebrovascular disease and
      coronary heart disease was significantly higher in the G3b group than in the G3a
      group. The brachial-ankle pulse wave velocity, which is one of the surrogate
      markers for atherosclerosis, was also significantly greater in the G3b group
      compared to the G3a group. CONCLUSION: The subdivision of the G3 stage in the
      revised classification proposed by the KDIGO is useful to evaluate the risk for
      diabetic vascular complications.

PMID- 22621777
TI  - Tauroursodeoxycholic acid suppresses amyloid beta-induced synaptic toxicity in
      vitro and in APP/PS1 mice.
AB  - Synapses are considered the earliest site of Alzheimer's disease (AD) pathology,
      where synapse density is reduced, and synaptic loss is highly correlated with
      cognitive impairment. Tauroursodeoxycholic acid (TUDCA) has been shown to be
      neuroprotective in several models of AD, including neuronal exposure to amyloid
      beta (Abeta) and amyloid precursor protein (APP)/presenilin 1 (PS1) double
      transgenic mice. Here, we show that TUDCA modulates synaptic deficits induced by
      Abeta in vitro. Specifically, TUDCA reduced the downregulation of the
      postsynaptic marker postsynaptic density-95 (PSD-95) and the decrease in
      spontaneous miniature excitatory postsynaptic currents (mEPSCs) frequency, while
      increasing the number of dendritic spines. This contributed to the induction of
      more robust and synaptically efficient neurons, reflected in inhibition of
      neuronal death. In vivo, TUDCA treatment of APP/PS1 mice abrogated the decrease
      in PSD-95 reactivity in the hippocampus. Taken together, these results expand the
      neuroprotective role of TUDCA to a synaptic level, further supporting the use of
      this molecule as a potential therapeutic strategy for the prevention and
      treatment of AD.

PMID- 22621779
TI  - Surgical site infections following colorectal cancer surgery: a randomized
      prospective trial comparing common and advanced antimicrobial dressing containing
      ionic silver.
AB  - BACKGROUND: An antimicrobial dressing containing ionic silver was found effective
      in reducing surgical-site infection in a preliminary study of colorectal cancer
      elective surgery. We decided to test this finding in a randomized, double-blind
      trial. METHODS: Adults undergoing elective colorectal cancer surgery at two
      university-affiliated hospitals were randomly assigned to have the surgical
      incision dressed with Aquacel Ag Hydrofiber dressing or a common dressing. To
      blind the patient and the nursing and medical staff to the nature of the dressing
      used, scrub nurses covered Aquacel Ag Hydrofiber with a common wound dressing in
      the experimental arm, whereas a double common dressing was applied to patients of
      control group. The primary end-point of the study was the occurrence of any
      surgical-site infection within 30 days of surgery. RESULTS: A total of 112
      patients (58 in the experimental arm and 54 in the control group) qualified for
      primary end-point analysis. The characteristics of the patient population and
      their surgical procedures were similar. The overall rate of surgical-site
      infection was lower in the experimental group (11.1% center 1, 17.5% center 2;
      overall 15.5%) than in controls (14.3% center 1, 24.2% center 2, overall 20.4%),
      but the observed difference was not statistically significant (P = 0.451), even
      with respect to surgical-site infection grade 1 (superficial) versus grades 2 and
      3, or grade 1 and 2 versus grade 3. CONCLUSIONS: This randomized trial did not
      confirm a statistically significant superiority of Aquacel Ag Hydrofiber dressing
      in reducing surgical-site infection after elective colorectal cancer surgery.
      TRIAL REGISTRATION: Clinicaltrials.gov: NCT00981110.

PMID- 22621780
TI  - Crataegus special extract WS((r))1442 prevents aging-related endothelial
      dysfunction.
AB  - Aging is associated with a markedly increased incidence of cardiovascular
      diseases due, in part, to the development of vascular endothelial dysfunction.
      The present study has evaluated whether the Crataegus special extract WS((r))1442
      prevents the development of aging-related endothelial dysfunction in rats, and,
      if so, to determine the underlying mechanisms. Wistar rats received either a
      control diet or the same diet containing 100 or 300 mg/kg/day of WS((r))1442 from
      week 25 until week 65. Vascular reactivity was assessed in mesenteric artery
      rings using organ chambers, oxidative stress by dihydroethidine staining and
      cyclooxygenase-1 (COX-1) and -2 (COX-2) expression by immunohistochemistry.
      Acetylcholine-induced endothelium-dependent relaxations in mesenteric artery
      rings were blunted in 65-week-old rats compared to 16-week-old rats. This effect
      was associated with a marked reduction of the endothelium-derived hyperpolarizing
      factor (EDHF) component whereas the nitric oxide (NO) component was not affected.
      Aging was also associated with the induction of endothelium-dependent contractile
      responses to acetylcholine. Both aging-related impairment of endothelium
      dependent relaxations and the induction of endothelium-dependent contractile
      responses were improved by the Crataegus treatment and by COX inhibitors. An
      excessive vascular oxidative stress and an upregulation of COX-1 and COX-2 were
      observed in the mesenteric artery of old rats compared to young rats, and these
      effects were improved by the Crataegus treatment. In conclusion, chronic intake
      of Crataegus prevented aging-related endothelial dysfunction by reducing the
      prostanoid-mediated contractile responses, most likely by improving the increased
      oxidative stress and the overexpression of COX-1 and COX-2.

PMID- 22621781
TI  - A self-adaptive foot-drop corrector using functional electrical stimulation (FES)
      modulated by tibialis anterior electromyography (EMG) dataset.
AB  - We developed a functional electrical stimulator for correcting the gait patterns
      of patients with foot-drop problem. The stimulating electrical pulses of the
      system are modulated to evoke contractions of the tibialis anterior muscle, by
      emulating the normal patterns. The modulation is adaptive, i.e. the system can
      predict the user's step frequency and the generated stimulation can match each
      step in real-time. In this study, step data from 11 young healthy volunteers were
      acquired, and five prediction algorithms were evaluated by the acquired data,
      including the average of Previous N steps (P-N), the Previous Nth step (P-Nth),
      General Regression Neural Network (GRNN), Autoregressive (AR) and Kalman filter
      (KF). The algorithm with the best efficiency-accuracy trade-off (P-N, when N=5)
      was implemented in the FES system. System evaluation results obtained from a post
      stroke patient with foot-drop showed that the system of this study demonstrated
      better performance on gait pattern correction than the methods widely adopted in
      commercial products.

PMID- 22621782
TI  - Needle-tissue interaction forces--a survey of experimental data.
AB  - The development of needles, needle-insertion simulators, and needle-wielding
      robots for use in a clinical environment depends on a thorough understanding of
      the mechanics of needle-tissue interaction. It stands to reason that the forces
      arising from this interaction are influenced by numerous factors, such as needle
      type, insertion speed, and tissue characteristics. However, exactly how these
      factors influence the force is not clear. For this reason, the influence of
      various factors on needle insertion-force was investigated by searching
      literature for experimental data. This resulted in a comprehensive overview of
      experimental insertion-force data available in the literature, grouped by factor
      for quick reference. In total, 99 papers presenting such force data were found,
      with typical peak forces in the order of 1-10N. The data suggest, for example,
      that higher velocity tends to decrease puncture force and increase friction.
      Furthermore, increased needle diameter was found to increase peak forces, and
      conical needles were found to create higher peak forces than beveled needles.
      However, many questions remain open for investigation, especially those
      concerning the influence of tissue characteristics.

PMID- 22621783
TI  - Cyclic AMP-Rap1A signaling activates RhoA to induce alpha(2c)-adrenoceptor
      translocation to the cell surface of microvascular smooth muscle cells.
AB  - Intracellular signaling by the second messenger cyclic AMP (cAMP) activates the
      Ras-related small GTPase Rap1 through the guanine exchange factor Epac. This
      activation leads to effector protein interactions, activation, and biological
      responses in the vasculature, including vasorelaxation. In vascular smooth muscle
      cells derived from human dermal arterioles (microVSM), Rap1 selectively regulates
      expression of G protein-coupled alpha(2C)-adrenoceptors (alpha(2C)-ARs) through
      JNK-c-jun nuclear signaling. The alpha(2C)-ARs are generally retained in the
      trans-Golgi compartment and mobilize to the cell surface and elicit
      vasoconstriction in response to cellular stress. The present study used human
      microVSM to examine the role of Rap1 in receptor localization. Complementary
      approaches included murine microVSM derived from tail arteries of C57BL6 mice
      that express functional alpha(2C)-ARs and mice deficient in Rap1A (Rap1A-null).
      In human microVSM, increasing intracellular cAMP by direct activation of adenylyl
      cyclase by forskolin (10 MUM) or selectively activating Epac-Rap signaling by the
      cAMP analog 8-pCPT-2'-O-Me-cAMP (100 MUM) activated RhoA, increased alpha(2C)-AR
      expression, and reorganized the actin cytoskeleton, increasing F-actin. The
      alpha(2C)-ARs mobilized from the perinuclear region to intracellular filamentous
      structures and to the plasma membrane. Similar results were obtained in murine
      wild-type microVSM, coupling Rap1-Rho-actin dynamics to receptor relocalization.
      This signaling was impaired in Rap1A-null murine microVSM and was rescued by
      delivery of constitutively active (CA) mutant of Rap1A. When tested in
      heterologous HEK293 cells, Rap1A-CA or Rho-kinase (ROCK-CA) caused translocation
      of functional alpha(2C)-ARs to the cell surface (~4- to 6-fold increase,
      respectively). Together, these studies support vascular bed-specific
      physiological role of Rap1 and suggest a role in vasoconstriction in microVSM.

PMID- 22621784
TI  - ZnT4 provides zinc to zinc-dependent proteins in the trans-Golgi network critical
      for cell function and Zn export in mammary epithelial cells.
AB  - Zinc (Zn) transporter 4 (ZnT4) plays a key role in mammary gland Zn metabolism. A
      mutation in ZnT4 (SLC30A4) that targets the protein for degradation is
      responsible for the "lethal milk" (lm/lm) mouse phenotype. ZnT4 protein is only
      detected in the secreting mammary gland, and lm/lm mice have ~35% less Zn in
      milk, decreased mammary gland size, and decreased milk secretion. However, the
      precise contribution of ZnT4 is unknown. We used cultured mouse mammary
      epithelial cells (HC11) and determined that ZnT4 was localized to the trans-Golgi
      network (TGN) and cell membrane and transported Zn from the cytoplasm. ZnT4
      mediated Zn import into the TGN directly contributed to labile Zn accumulation as
      ZnT4 overexpression increased FluoZin3 fluorescence. Moreover, ZnT4 provided Zn
      for metallation of galactosyltransferase, a Zn-dependent protein localized within
      the TGN that is critical for milk secretion, and carbonic anhydrase VI, a Zn
      dependent protein secreted from the TGN into milk. We further noted that ZnT4
      relocalized to the cell membrane in response to Zn. Together these studies
      demonstrated that ZnT4 transports Zn into the TGN, which is critical for key
      secretory functions of the mammary cell.

PMID- 22621785
TI  - Soluble epoxide hydrolase expression in a porcine model of arteriovenous graft
      stenosis and anti-inflammatory effects of a soluble epoxide hydrolase inhibitor.
AB  - Synthetic arteriovenous (AV) grafts, placed between an artery and vein, are used
      for hemodialysis but often fail due to stenosis, typically at the vein-graft
      anastomosis. This study recorded T lymphocyte and macrophage accumulation at the
      vein-graft anastomosis, suggesting a role for inflammation in stenosis
      development. Epoxyeicosatrienoic acids (EETs), products of cytochrome P-450
      epoxidation of arachidonic acid, have vasculoprotective and anti-inflammatory
      effects including inhibition of platelet activation, cell migration, and
      adhesion. EETs are hydrolyzed by soluble epoxide hydrolase (sEH) to less active
      diols. The effects of a specific inhibitor of sEH (sEHI) on cytokine release from
      human monocytes and mouse bone marrow-derived macrophages (BMMPhi) from wild-type
      (WT) and sEH knockout (KO) animals were investigated. Expression of sEH protein
      increased over time at the anastomosis as evaluated by immunohistochemistry. Pre
      exposure of adherent human monocytes to sEHI (5 MUM) significantly inhibited
      lipopolysaccharide-induced release of monocyte chemotactic protein-1 (MCP-1) and
      tumor necrosis factor-alpha and enhanced the EET-to-diol ratio. Release of MCP-1
      from WT BMMPhi was significantly inhibited but release from sEH KO BMMPhi was not
      attenuated indicating the specificity of the sEHI. In contrast, sEHI did not
      inhibit the release of macrophage inflammatory protein-1 or interleukin-6.
      Nuclear translocation of NF-kappaB, as assessed by immunocytochemical staining,
      was not decreased with sEHI in monocytes, but the phosphorylation of JNK was
      completely abrogated, suggesting this pathway is the target of sEHI effects in
      monocytes. These results suggest that sEHI may be useful for inhibition of
      inflammation and subsequently stenosis in AV grafts.

PMID- 22621786
TI  - Functional dissociation between PIKfyve-synthesized PtdIns5P and PtdIns(3,5)P2 by
      means of the PIKfyve inhibitor YM201636.
AB  - PIKfyve is an essential mammalian lipid kinase with pleiotropic cellular
      functions whose genetic knockout in mice leads to preimplantation lethality.
      Despite several reports for PIKfyve-catalyzed synthesis of phosphatidylinositol 5
      phosphate (PtdIns5P) along with phosphatidylinositol-3,5-biphosphate
      [PtdIns(3,5)P(2)] in vitro and in vivo, the role of the PIKfyve pathway in
      intracellular PtdIns5P production remains underappreciated and the function of
      the PIKfyve-synthesized PtdIns5P pool poorly characterized. Hence, the recently
      discovered potent PIKfyve-selective inhibitor, the YM201636 compound, has been
      solely tested for inhibiting PtdIns(3,5)P(2) synthesis. Here, we have compared
      the in vitro and in vivo inhibitory potency of YM201636 toward PtdIns5P and
      PtdIns(3,5)P(2). Unexpectedly, we observed that at low doses (10-25 nM), YM201636
      inhibited preferentially PtdIns5P rather than PtdIns(3,5)P(2) production in
      vitro, whereas at higher doses, the two products were similarly inhibited. In
      cellular contexts, YM201636 at 160 nM inhibited PtdIns5P synthesis twice more
      effectively compared with PtdIns(3,5)P(2) synthesis. In 3T3L1 adipocytes, human
      embryonic kidney 293 and Chinese hamster ovary (CHO-T) cells, levels of PtdIns5P
      dropped by 62-71% of the corresponding untreated controls, whereas those of
      PtdIns(3,5)P(2) fell by only 28-46%. The preferential inhibition of PtdIns5P
      versus PtdIns(3,5)P(2) at low doses of YM201636 was explored to probe
      contributions of the PIKfyve-catalyzed PtdIns5P pool to insulin-induced actin
      stress fiber disassembly in CHO-T cells, GLUT4 translocation in 3T3L1 adipocytes,
      and induction of aberrant cellular vacuolation in these or other cell types. The
      results provide the first experimental evidence that the principal pathway for
      PtdIns5P intracellular production is through PIKfyve and that insulin effect on
      actin stress fiber disassembly is mediated entirely by the PIKfyve-produced
      PtdIns5P pool.

PMID- 22621787
TI  - Modulation of endothelial SK3 channel activity by Ca2+dependent caveolar
      trafficking.
AB  - Small- and intermediate-conductance Ca(2+)-activated K(+) channels (SK3/Kcnn3 and
      IK1/Kcnn4) are expressed in vascular endothelium. Their activities play important
      roles in regulating vascular tone through their modulation of intracellular
      concentration ([Ca(2+)](i)) required for the production of endothelium-derived
      vasoactive agents. Activation of endothelial IK1 or SK3 channels hyperpolarizes
      endothelial cell membrane potential, increases Ca(2+) influx, and leads to the
      release of vasoactive factors, thereby impacting blood pressure. To examine the
      distinct roles of IK1 and SK3 channels, we used electrophysiological recordings
      to investigate IK1 and SK3 channel trafficking in acutely dissociated endothelial
      cells from mouse aorta. The results show that SK3 channels undergo Ca(2+)
      dependent cycling between the plasma membrane and intracellular organelles;
      disrupting Ca(2+)-dependent endothelial caveolae cycling abolishes SK3 channel
      trafficking. Moreover, transmitter-induced changes in SK3 channel activity and
      surface expression modulate endothelial membrane potential. In contrast, IK1
      channels do not undergo rapid trafficking and their activity remains unchanged
      when either exo- or endocytosis is block. Thus modulation of SK3 surface
      expression may play an important role in regulating endothelial membrane
      potential in a Ca(2+)-dependent manner.

PMID- 22621788
TI  - Molecular characterisation of sinonasal carcinomas and their clinical
      implications.
AB  - Sinonasal carcinomas are rare tumours with an unfavourable prognosis whose
      management is difficult and complex, leading to high morbidity and mortality
      despite improvements in the field of surgery and radiotherapy. An elevated number
      of these tumours can be attributed to occupational exposure. In comparison with
      other head and neck malignancies, studies of molecular changes in these tumours
      are infrequent. This review was focused on findings about the epidemiology and
      molecular and phenotypic characterisation of sinonasal carcinomas, which can
      potentially be useful for diagnosis and treatment. The increasing knowledge about
      the molecular biology that underlies their carcinogenesis may help to identify
      precursor lesions, prognostic markers and markers that predict chemoradiotherapy
      response and, finally, to identify potential molecular targets that will expand
      treatment options. 

PMID- 22621790
TI  - A patient with ulcerative colitis and central serous chorioretinopathy--a
      therapeutic dilemma.
AB  - We report a case of a patient with ulcerative colitis and central serous
      retinopathy, which is a chronic ophthalmological condition that is frequently
      aggravated by corticosteroid treatment and may sometimes result in severe visual
      impairment. This case represents an interesting therapeutic dilemma pertaining to
      the treatment of ulcerative colitis exacerbation in a patient with this rare
      condition. Awareness of this condition as a cause of visual disturbance in IBD
      patients and a close ophthalmological cooperation are required in order to
      provide the optimal care for these patients.

PMID- 22621791
TI  - Perceived levels of pain associated with bone marrow aspirates and biopsies.
AB  - BACKGROUND: Little is known about the degree of pain experienced by patients
      undergoing a bone marrow aspiration and biopsy (BMAB). OBJECTIVE: To evaluate the
      effectiveness of several strategies aimed at reducing the pain score. METHODS: We
      conducted a retrospective analysis of 258 consecutive adult patients who
      underwent BMAB via 6 different approaches, the first 5 of which were performed by
      one physician. Group A received local anesthesia with 1% lidocaine hydrochloride
      (5 mL) and a 5-minute wait time before the procedure; group B received local
      anesthesia with a double dose (10 mL) of lidocaine; group C received 5 mL of
      local anesthesia with a 10-minute wait; group D received 5 mL of local anesthesia
      plus a topical spray with ethyl chloride; group E received oral analgesia and
      anxiolysis 30 minutes before the procedure in addition to the group A dosage of
      lidocaine; and group F received the same anesthesia as did group A, but the BMAD
      was performed by a less experienced practitioner. RESULTS: On a 0 to 10 scale,
      the mean pain level among the 258 patients was 3.2 (standard deviation = 2.6).
      Rate of complications was low (<1%). Several strategies failed to improve the
      pain level, including the administration of a double dose of local anesthesia,
      waiting longer for the anesthesia effect, and the additional use of a topical
      anesthetic spray or oral analgesia and anxiolysis. Pain levels were not increased
      when the procedure was done by a less experienced practitioner. Younger age and
      female gender were associated with higher pain levels. CONCLUSIONS: Given that
      the average level of perceived pain during BMAB is low to moderate (approximately
      3 on a 0-10 scale), the routine use of conscious sedation for this procedure may
      not be indicated. Several strategies aimed at reducing the pain level, including
      doubling the dose of anesthesia and using an oral prophylactic regimen of
      analgesia and anxiolysis, failed to improve pain scores.

PMID- 22621792
TI  - Biopsychosocial predictors of postmenopausal dyspareunia: the role of steroid
      hormones, vulvovaginal atrophy, cognitive-emotional factors, and dyadic
      adjustment.
AB  - INTRODUCTION: Although dyspareunia experienced after menopause is widely
      attributed to declining estrogen levels and vulvovaginal atrophy, critical
      reviews of the literature have suggested that these factors are incomplete as
      explanatory mechanisms. Little is known about psychosocial factors that may also
      be implicated in postmenopausal dyspareunic pain. AIM: To determine the extent to
      which levels of estrogens and progesterone, vulvovaginal atrophy, cognitive
      emotional factors, and dyadic adjustment are predictive of postmenopausal
      dyspareunic pain intensity. METHODS: A total of 182 postmenopausal dyspareunia
      sufferers underwent a structured interview concerning sociodemographic status as
      well as medical and pain histories, gynecological examination, cytological
      evaluation, a blood draw, and answered a series of self-report questionnaires.
      Given the large number of genital and pelvic pain variables measured, a principal
      components analysis was undertaken to identify a smaller number of components
      representing meaningful dimensions of genital and pelvic pain. MAIN OUTCOME
      MEASURES: Pain severity ratings during intercourse were obtained using the McGill
      Pain Questionnaire. Pain ratings were also obtained during gynecological
      assessment. Serum estrone, estradiol, and progesterone levels were measured via
      immunoassay. The Vaginal Atrophy Index and maturation value were used to
      determine vulvovaginal atrophy severity. Participants completed the Pain
      Catastrophizing Scale, State-Trait Anxiety Inventory, The Beck Depression
      Inventory-II, and Dyadic Adjustment Scale. RESULTS: Hormone levels were not found
      to be consistent predictors of pain severity. Maturation value and cognitive
      emotional variables (e.g., catastrophization, depression, anxiety) were
      significant predictors of vestibular pain, which affected over 90% of our sample.
      Relationship adjustment variables were inversely associated with pain severity
      within several genital locations. CONCLUSIONS: Results suggest that the
      traditional hypoestrogen and vulvovaginal atrophy conceptualization of
      postmenopausal dyspareunia is an insufficient explanatory model, and that pain is
      also influenced by cognitive, affective, and dyadic factors.

PMID- 22621793
TI  - Reverse shoulder arthroplasty components and surgical techniques that restore
      glenohumeral motion.
AB  - BACKGROUND: Modifications in reverse shoulder arthroplasty (RSA) have been made
      with the intent of maximizing motion, although there is little objective evidence
      outlining their benefit. This study investigated the RSA component combinations
      that impart the greatest effect on impingement-free glenohumeral motion. METHODS:
      A previously validated virtual shoulder model was implanted with RSA components
      that varied by humeral implant type (inset/onset), glenosphere diameter (30, 36,
      and 42 mm), glenosphere placement (inferior/neutral), glenosphere center-of
      rotation offset (0, 5, and 10 mm), humeral neck-shaft angle (130 degrees  and 150
      degrees ), and humeral offset (zero, five, and ten mm). Motion was simulated in
      all technique combinations until the point of impingement in abduction,
      flexion/extension (F/E), and internal/external rotation (IR/ER). Regression
      analysis was used to rank combinations based on motion. RESULTS: Of 216 possible
      study combinations, 126 constructs (58%) demonstrated no arm-at-side impingement
      and were included for analysis. Models with the largest motion in abduction, F/E,
      and IR/ER, respectively, were inset-42-inferior-10-150-zero (107 degrees ), inset
      36-inferior-10-130-five (146 degrees ), and inset-42-inferior-10-130-ten (121
      degrees ). Humeral neck-shaft angle, glenosphere center-of-rotation offset,
      glenosphere placement, and glenosphere diameter had a significant effect on
      motion in all planes tested. Of these variables, humeral neck-shaft angle was
      most predictive of a change in abduction and F/E motion, whereas glenosphere
      placement was most predictive of a change in IR/ER motion. CONCLUSION: Higher
      glenosphere center-of-rotation offsets led to an increase in motion in all
      planes. To maximize motion in abduction, a valgus humeral component should be
      selected; to maximize F/E, a varus humeral component should be selected; and, to
      maximize IR/ER, the glenosphere should be placed inferiorly.

PMID- 22621794
TI  - Detection of hemorrhage source: the diagnostic value of post-mortem CT
      angiography.
AB  - The aim of this study was to compare the diagnostic value of post-mortem computed
      tomography angiography (PMCTA) to conventional, ante-mortem computed tomography
      (CT)-scan, CT-angiography (CTA) and digital subtraction angiography (DSA) in the
      detection and localization of the source of bleeding in cases of acute hemorrhage
      with fatal outcomes. The medical records and imaging scans of nine individuals
      who underwent a conventional, ante-mortem CT-scan, CTA or DSA and later died in
      the hospital as a result of an acute hemorrhage were reviewed. Post-mortem
      computed tomography angiography, using multi-phase post-mortem CTA, as well as
      medico-legal autopsies were performed. Localization accuracy of the bleeding was
      assessed by comparing the diagnostic findings of the different techniques. The
      results revealed that data from ante-mortem and post-mortem radiological
      examinations were similar, though the PMCTA showed a higher sensitivity for
      detecting the hemorrhage source than did ante-mortem radiological investigations.
      By comparing the results of PMCTA and conventional autopsy, much higher
      sensitivity was noted in PMCTA in identifying the source of the bleeding. In
      fact, the vessels involved were identified in eight out of nine cases using PMCTA
      and only in three cases through conventional autopsy. Our study showed that
      PMCTA, similar to clinical radiological investigations, is able to precisely
      identify lesions of arterial and/or venous vessels and thus determine the source
      of bleeding in cases of acute hemorrhages with fatal outcomes.

PMID- 22621795
TI  - Intervention to improve adherence to lipid-lowering medication and lipid-levels
      in patients with an increased cardiovascular risk.
AB  - Low levels of statin adherence may compromise treatment outcomes. The aim of this
      study was to investigate whether nurse-led cardiovascular risk-factor counseling
      could improve statin adherence and lipid levels without increasing patients'
      anxiety. Patients with indications for statin therapy for primary or secondary
      prevention of cardiovascular disease were randomly assigned to receive routine
      care or extended care (EC) at baseline and at months 3, 9, and 18. Patients in
      the EC group received a personalized risk-factor passport, showing modifiable and
      unmodifiable individual risk factors and a graphical presentation of their
      calculated absolute 10-year cardiovascular disease risk as well as the target
      risk that could be reached if all modifiable risk factors were optimally treated.
      Lipid levels were assessed at each visit. Carotid intima-media thickness was
      measured at baseline and at month 18. Adherence, anxiety, quality of life,
      symptoms, and smoking status were assessed using a self-administered
      questionnaire at each visit. A total of 201 patients were included in the study.
      Statin adherence was significantly higher (p <0.01) and anxiety was significantly
      lower (p <0.01) in the EC group than in the routine care group. Low-density
      lipoprotein cholesterol was statistically significantly lower in the EC group
      than in the routine group (2.66 vs 3.00 mmol/L, respectively, p = 0.024) in
      primary prevention patients only. Intima-media thickness improved significantly
      from baseline (p <0.01) in all patients, irrespective of group assignment. In
      conclusion, cardiovascular risk-factor counseling resulted in improved lipid
      profiles in primary prevention patients and higher levels of adherence to statins
      and lower levels of anxiety in all patients.

PMID- 22621796
TI  - Evaluation of low-density lipoprotein particle number distribution in patients
      with type 2 diabetes mellitus with low-density lipoprotein cholesterol <50 mg/dl
      and non-high-density lipoprotein cholesterol <80 mg/dl.
AB  - Many patients with type 2 diabetes mellitus (T2DM) have relatively normal levels
      of low-density lipoprotein (LDL) cholesterol yet have increased risk for
      cardiovascular events. Distribution of lipoprotein subclasses in patients with
      T2DM who have achieved very low levels of LDL cholesterol (<50 mg/dl) or non-high
      density lipoprotein (HDL) cholesterol (<80 mg/dl) have not been extensively
      examined. The aim of this study was to assess variations in lipoprotein particle
      concentration in patients with diabetes with "very low" LDL cholesterol and non
      HDL cholesterol levels to elucidate the drivers of residual cardiovascular risk.
      Data were selected from a single large clinical laboratory database. Cases were
      patients with T2DM diagnosis codes (International Classification of Diseases,
      Ninth Revision, codes 250 to 250.93). Lipoprotein particle concentrations were
      analyzed using nuclear magnetic resonance spectroscopy. The Friedewald equation
      was used to calculate LDL cholesterol. Among the 1,970 patients with T2DM, the
      mean age was 61 years, and approximately 51% were men. At LDL cholesterol
      concentrations <50 mg/dl (triglyceride <150 mg/dl and HDL cholesterol >40 mg/dl),
      16% had LDL particle concentrations <500 nmol/L, 70% had concentrations of 500 to
      1,000 nmol/L, and 14% had concentrations >1,001 nmol/L. At non-HDL cholesterol
      levels <80 mg/dl, 8% had LDL particle concentrations <500 nmol/L, 67% had
      concentrations of 500 to 1,000 nmol/L, and 25% had concentrations >1,001 nmol/L.
      In conclusion, despite attainment of LDL cholesterol <50 mg/dl or non-HDL
      cholesterol <80 mg/dl, patients with diabetes exhibited significant variation in
      LDL particle levels, with most having LDL particle concentrations >500 nmol/L,
      suggesting the persistence of potential residual coronary heart disease risk.

PMID- 22621798
TI  - Formulating an answerable question, displaying data, illustrating, writing,
      reviewing, and editing manuscripts for publication in medical journals.

PMID- 22621797
TI  - A new scoring system for evaluating the risk of heart failure events in Japanese
      patients with atrial fibrillation.
AB  - Risk stratification for heart failure (HF) in patients with atrial fibrillation
      (AF) has not been well established. The aim of this study was to identify the
      predictors of HF events in patients with AF, consequently developing a new risk
      scoring system that stratifies the risk for HF events. In this prospective,
      single hospital-based cohort, all patients who presented from July 2004 to March
      2010 were registered (Shinken Database 2004-2009). Follow-up was maintained by
      being linked to the medical records or by sending study documents of prognosis.
      Of the 13,228 patients in the Shinken Database 2004-2009, 1,942 patients with AF
      were identified. Of the patients with AF, HF events (hospitalization or death
      from HF) occurred in 147 patients (7.6%) during a mean follow-up period of 776 +/
      623 days. After identifying the parameters that were independently associated
      with the incidence of HF events (coexistence of organic heart diseases, anemia
      [hemoglobin level <11 g/dl], renal dysfunction [estimated glomerular filtration
      rate <60 ml/min/m(2)], diabetes mellitus, and the use of diuretics), a new
      scoring system was developed, the H(2)ARDD score (heart diseases = 2 points,
      anemia = 1 point, renal dysfunction = 1 point, diabetes = 1 point, and diuretic
      use = 1 point; range 0 to 6 points). This scoring system discriminated the low-
      and high-risk populations well (incidence in patients scoring 0 and 6 points of
      0.2% and 40.8% per patient-year, respectively) and showed high predictive ability
      (area under the curve 0.840, 95% confidence interval 0.803 to 0.876). In
      conclusion, the new H(2)ARDD score may help identify the population of patients
      with AF at high risk for HF events.

PMID- 22621799
TI  - Comparison of effectiveness of ranolazine plus amiodarone versus amiodarone alone
      for conversion of recent-onset atrial fibrillation.
AB  - Ranolazine, an antianginal agent with antiarrhythmic properties, prevents atrial
      fibrillation (AF) in patients with acute coronary syndrome. In experimental
      models, the combination of ranolazine and amiodarone has marked synergistic
      effects that potently suppress AF. Currently, the clinical effect of the
      ranolazine-amiodarone combination for the conversion of AF is unknown. This
      prospective randomized pilot study compared the safety and efficacy of ranolazine
      plus amiodarone versus amiodarone alone for the conversion of recent-onset AF. We
      enrolled 51 consecutive patients with AF (<48-hour duration) eligible for
      pharmacologic cardioversion. Patients (33 men, 63 +/- 8 years of age) were
      randomized to intravenous amiodarone for 24 hours (group A, n = 26) or to
      intravenous amiodarone plus oral ranolazine 1,500 mg at time of randomization
      (group A + R, n = 25). The 2 groups were well balanced with respect to clinical
      characteristics and left atrial diameter. Conversion within 24 hours (primary end
      point) was achieved in 22 patients (88%) in group A + R versus 17 patients (65%)
      in group A (p = 0.056). Time to conversion was shorter in group A + R than in
      group A (9.8 +/- 4.1 vs 14.6 +/- 5.3 hours, p = 0.002). According to Cox
      regression analysis, left atrial diameter and A + R treatment were the only
      independent predictors of time to conversion (hazard ratio 5.35, 95% confidence
      interval 2.37 to 12.11, p <0.001; hazard ratio 0.81, 95% confidence interval 0.74
      to 0.88, p <0.001, respectively). There were no proarrhythmic events in either
      group. In conclusion, addition of ranolazine to standard amiodarone therapy is
      equally safe and appears to be more effective compared to amiodarone alone for
      conversion of recent-onset AF.

PMID- 22621800
TI  - Frequency and outcomes of cardiac operations and catheter interventions in Turner
      syndrome.
AB  - Cardiac malformations occur commonly in Turner syndrome (TS), but the outcomes of
      cardiac operations and catheter-based procedures are unknown. The Pediatric
      Cardiac Care Consortium database was queried for individuals with TS and other
      female subjects without genetic abnormalities or syndromes (non-TS [NTS]).
      Procedures for left-sided heart lesions represented most TS procedures (95.2%).
      Three hundred ninety-eight patients with TS who underwent 637 of these procedures
      of interest were compared with 25,913 female NTS subjects who underwent 56,625
      procedures. The numbers of procedures per admission (1.47 vs 1.61, p = 0.01) and
      per patient (1.85 vs 2.16, p <0.0001) were significantly lower in patients with
      TS. Procedures for cyanotic heart disease other than hypoplastic left heart (HLH)
      were performed 4.5-fold less frequently in patients with TS. Patients with TS and
      NTS subjects had equivalent hospital lengths of stay, except for patients with TS
      who underwent hypoplastic aortic arch operations, patent ductus arteriosus
      ligation, pulmonary artery balloon dilation, balloon atrial septostomy, and
      catheter closure of atrial septal defects. There were 34 deaths among patients
      with TS and 1,795 among NTS subjects (8.6% vs 7.2%, p = 0.30). When HLH was
      excluded, mortality was lower in the TS group (3.9% vs 6.5%, p = 0.05).
      Operations for partial anomalous pulmonary venous connection (14.3% vs 1.9%, p =
      0.03) and HLH (90.4% vs 70.5%, p = 0.08) were more likely to result in death in
      patients with TS. In conclusion, given generally comparable lengths of stay and
      numbers of procedures as well as uniformly excellent results, these data suggest
      that the diagnosis of TS does not increase the utilization of limited health care
      resources. Operations for HLH and partial anomalous pulmonary vein connection
      carry additional risk for those with TS. These results will permit risk
      stratification, prognostication, and counseling of individuals with TS and their
      families.

PMID- 22621801
TI  - Prediction of new onset atrial fibrillation after cardiac revascularization
      surgery.
AB  - The aim of this study was to create a simple risk index to predict new-onset
      atrial fibrillation (AF) after coronary artery bypass grafting in patients with
      histories of AF. AF after coronary artery bypass grafting (referred to here as
      AF) is associated with increased morbidity and mortality. Identifying patients at
      high risk for developing AF may help identify a group of patients who might
      benefit from strategies to prevent postoperative AF. A cohort of 18,517 patients
      enrolled from January 1, 1996, to December 31, 2009, was used to derive a risk
      index for AF prediction. A multivariate logistic regression model determined the
      independent predictive impact of clinical and demographic characteristics on the
      occurrence of AF. A subset of these variables was used to construct a risk index
      to predict AF. This risk index was validated in a sequential cohort of 1,378
      consecutive patients who underwent coronary artery bypass grafting from January
      1, 2010, to June 30, 2011. AF occurred in 3,486 patients in the calibration
      cohort (18.83%) and in 269 patients in the validation cohort (19.52%). After
      considering patients' demographics, co-morbid conditions, and severity of
      illness, advanced age appeared as the most powerful predictor of AF (odds ratio
      1.059/year, 95% confidence interval 1.055 to 1.063). Age, height, weight, and the
      presence of peripheral vascular disease contributed most to the prediction model.
      An AF risk index including these variables had adequate discriminatory power,
      with a concordance index of 0.68. In conclusion, using a large cohort of
      patients, a simple risk index relying only on preoperative clinical variables was
      developed, which will help predict AF. This risk index can be used clinically to
      identify patients at high risk for the development of AF.

PMID- 22621802
TI  - Progress curve mechanistic modeling approach for assessing time-dependent
      inhibition of CYP3A4.
AB  - A progress curve method for assessing time-dependent inhibition of CYP3A4 is
      based on simultaneous quantification of probe substrate metabolite and inhibitor
      concentrations during the experiment. Therefore, it may overcome some of the
      issues associated with the traditional two-step method and estimation of
      inactivation rate (k(inact)) and irreversible inhibition (K(I)) constants. In the
      current study, seven time-dependent inhibitors were investigated using a progress
      curve method and recombinant CYP3A4. A novel mechanistic modeling approach was
      applied to determine inhibition parameters using both inhibitor and probe
      metabolite data. Progress curves generated for clarithromycin, erythromycin,
      diltiazem, and N-desmethyldiltiazem were described well by the mechanistic
      mechanism-based inhibition (MBI) model. In contrast, mibefradil, ritonavir, and
      verapamil required extension of the model and inclusion of competitive inhibition
      term for the metabolite. In addition, this analysis indicated that verapamil
      itself causes minimal MBI, and the formation of inhibitory metabolites was
      responsible for the irreversible loss of CYP3A4 activity. The k(inact) and K(I)
      estimates determined in the current study were compared with literature data
      generated using the conventional two-step method. In the current study, the
      inactivation efficiency (k(inact)/K(I)) for clarithromycin, ritonavir, and
      erythromycin were up to 7-fold higher, whereas k(inact)/K(I) for mibefradil, N
      desmethyldiltiazem, and diltiazem were, on average, 2- to 4.8-fold lower than
      previously reported estimates. Use of human liver microsomes instead of
      recombinant CYP3A4 resulted in 5-fold lower k(inact)/K(I) for erythromycin. In
      conclusion, the progress curve method has shown a greater mechanistic insight
      when determining kinetic parameters for MBI in addition to providing a more
      comprehensive experimental protocol.

PMID- 22621803
TI  - A novel ring oxidation of 4- or 5-substituted 2H-oxazole to corresponding 2
      oxazolone catalyzed by cytosolic aldehyde oxidase.
AB  - The ring oxidation of 2H-oxazole, or C2-unsubstituted oxazole, to 2-oxazolone, a
      cyclic carbamate, was observed on various 4- or 5-substituted oxazoles. Using 5
      (3-bromophenyl)oxazole as a model compound, its 2-oxazolone metabolite M1 was
      fully characterized by liquid chromatography/tandem mass spectrometry and nuclear
      magnetic resonance. The reaction mainly occurred in the liver cytosolic fraction
      without the requirement of cytochrome P450 enzymes and cofactor NADPH.
      Investigations into the mechanism of formation of 2-oxazolone using various
      chemical inhibitors indicated that the reaction was primarily catalyzed by
      aldehyde oxidase and not by xanthine oxidase. In addition, cytosol incubation of
      5-(3-bromophenyl)oxazole in the medium containing H218O led to the 18O
      incorporation into M1, substantiating the reaction mechanism of a typical
      molybdenum hydroxylase. The rank order of liver cytosols for the 2-oxazolone
      formation was mouse > monkey ? rat and human liver cytosol, whereas M1 was not
      formed in dog liver cytosol. Because the reaction was observed with a number of 4
      or 5-substituted 2H-oxazoles in mouse liver cytosols, 2H-oxazoles represent a
      new substrate chemotype for ring oxidation catalyzed by aldehyde oxidase.

PMID- 22621804
TI  - Changes in teachers' smoking behaviour following enforcement of a total smoke
      free school policy.

PMID- 22621805
TI  - Human papillomavirus infection in Macau women.
AB  - OBJECTIVE: To investigate the prevalence and genotypes of human papillomavirus
      (HPV) infection in Macau women. STUDY DESIGN: Female patients presenting for a
      medical consultation or medical check-up were recruited with informed consent.
      METHODS: Cytology and HPV-DNA genotyping were performed on 402 cervical specimens
      that were collected from Macau women. RESULTS: Of the specimens, 29.9% were found
      to be HPV-DNA positive; 26.4% were infected with one HPV genotype, while 3.0% and
      0.5% were infected with two and three HPV genotypes, respectively. The most
      prevalent HPV genotype was type 52 (11.1%), followed by type 16 (9.7%). Both
      types 51 and 62 ranked third (9.0%). CONCLUSIONS: The HPV infection rate in Macau
      appears to be higher than that in the neighbouring city of Hong Kong. The most
      prevalent genotypes were similar to those in South-west and Southern China.

PMID- 22621806
TI  - A novel sialyl Le(X) expression score as a potential prognostic tool in
      colorectal cancer.
AB  - BACKGROUND: Treatment decisions in colorectal cancer subsequent to surgery are
      based mainly on the TNM system. There is a need to establish novel prognostic
      markers based on the molecular characterization of tumor cells. Evidence exists
      that sialyl Le(X) expression is correlated with an unfavorable outcome in
      colorectal cancer. The aim of this study was to establish a simple sialyl Le(X)
      staining score and to determine a potential correlation with the prognosis in a
      series of advanced colorectal carcinoma patients. METHODS: In order to implement
      routine use of sialyl Le(X) immunohistology, we established a new, easily
      reproducible score and defined a cutoff which discriminated groups with better or
      worse outcome, respectively. We then correlated sialyl Le(X) expression of 215
      UICC stage III and IV patients with disease-free and cancer-related survival.
      RESULTS: A five-stage score could be established based on automated
      immunohistochemical stainings. Using a statistical model, we calculated a cutoff
      to discriminate between weak and strong staining positivity of sialyl Le(X).
      Patients with strong positive specimens had a worse cancer-related survival (P =
      0.004) but no difference was observed for disease-free survival (P = 0.352).
      CONCLUSIONS: These results demonstrate a strong correlation between high sialyl
      Le(X)-expression in colorectal carcinomas and cancer-related survival. Our highly
      standardized and easy-to-use staining score is suitable for routine use and hence
      it could be recommended to evaluate sialyl Le(X)-expression as part of the
      standard histopathological analysis of colorectal carcinomas and to validate the
      score prospectively based on a larger population.

PMID- 22621807
TI  - Effects of packing rates of cubic-shaped polyurethane foam carriers on the
      microbial community and the removal of organics and nitrogen in moving bed
      biofilm reactors.
AB  - The effects of packing rates (20%, 30%, and 40%) of polyurethane foam (PUF) to
      the removal of organics and nitrogen were investigated by continuously feeding
      artificial sewage in three aerobic moving bed biofilm reactors. The results
      indicated that the packing rate of the PUF carriers had little influence on the
      COD removal efficiency (81% on average). However, ammonium removal was affected
      by the packing rates, which was presumably due to the different relative
      abundances of nitrifying bacteria. A high ammonium removal efficiency of 96.3% at
      a hydraulic retention time of 5h was achieved in 40% packing rate reactor,
      compared with 37.4% in 20% packing rate. Microprofiles of dissolved oxygen and
      nitrate revealed that dense biofilm limits the DO transfer distance and nitrate
      diffusion. Pyrosequencing analysis of the biofilm showed that Proteobacteria,
      Bacteroidetes and Verrucomicrobia were the three most abundant phyla, but the
      proportions of the microbial community varied with the packing rate of the PUF
      carriers.

PMID- 22621808
TI  - Production of vinyl derivatives from alkaline hydrolysates of corn cobs by
      recombinant Escherichia coli containing the phenolic acid decarboxylase from
      Lactobacillus plantarum CECT 748T.
AB  - The enzyme PAD from Lactobacillus plantarum CECT 748T decarboxylates some
      cinnamic acids namely p-coumaric acid (p-CA), caffeic acid (CA), and ferulic acid
      (FA) into their corresponding 4-vinyl derivatives (4-VD): 4-vinyl phenol (4-VP),
      4-vinyl catechol (4-VC), and 4-vinyl guaiacol (4-VG), respectively, which are
      valuable food additives mainly employed as flavouring agents. The gene encoding
      this enzyme was cloned and overexpressed in Escherichia coli. Recombinant E. coli
      cells overproducing L. plantarum PAD showed a preference to degrade mainly p-CA
      and CA. Sterilized liquors obtained after alkaline hydrolysis of corn cob or
      alkaline hydrolysis of the solid residue coming from acid hydrolysis of corn cob
      were employed as growth media in fermentations performed in shaker or bioreactor.
      The fermentative process allowed converting 2222.8 mg/L p-CA into 993.9 mg/L 4
      VP. The process described here allowed the production with a high-yield of a
      valuable food additive from a by-product of the food industry.

PMID- 22621809
TI  - Characteristics of extracellular polymeric substances and bacterial communities
      in an anaerobic membrane bioreactor coupled with online ultrasound equipment.
AB  - Two parallel anaerobic membrane bioreactors (MBRs), integrated with or without
      ultrasound equipment for online membrane fouling control (US-AnMBR, or AnMBR)
      were established to digest waste activated sludge (WAS). The characteristics of
      bound extracellular polymeric substances (EPS) and bacterial communities in the
      systems were investigated for further understanding of the membrane fouling
      mechanisms. Ultrasound was an effective method for reducing cake layer
      resistance. A relatively high amount of bound EPS were found in the cake layer,
      especially for the US-AnMBR, by responding to the external forces (i.e. cross
      flow and ultrasound). High-throughput pyrosequencing and denaturing gradient gel
      electrophoresis (DGGE) were applied to analyze the bacterial diversity. Some
      bacterial populations contributing to membrane fouling were identified to
      accumulate in the cake layer, such as Peptococcaceae, Bacteroides and
      Syntrophobacterales. Since the ultrasounded retentate was recirculated back to
      the reactor, the bacterial community in the digested sludge was affected.

PMID- 22621810
TI  - Single-step syngas-to-distillates (S2D) process based on biomass-derived syngas-
      a techno-economic analysis.
AB  - This study compared biomass gasification based syngas-to-distillate (S2D) systems
      using techno-economic analysis (TEA). Three cases, state of technology (SOT),
      goal, and conventional, were compared in terms of performance and cost. The SOT
      case represented the best available experimental results for a process starting
      with syngas using a single-step dual-catalyst reactor for distillate generation.
      The conventional case mirrored a conventional two-step S2D process consisting of
      separate syngas-to-methanol and methanol-to-gasoline (MTG) processes. The goal
      case assumed the same performance as the conventional, but with a single-step S2D
      technology. TEA results revealed that the SOT was more expensive than the
      conventional and goal cases. The SOT case suffers from low one-pass yield and
      high selectivity to light hydrocarbons, both of which drive up production cost.
      Sensitivity analysis indicated that light hydrocarbon yield and single pass
      conversion efficiency were the key factors driving the high cost for the SOT
      case.

PMID- 22621811
TI  - The effects of phenoseason and storm characteristics on throughfall solute
      washoff and leaching dynamics from a temperate deciduous forest canopy.
AB  - Seasonal variations in the washoff and leaching dynamics of throughfall ionic
      fluxes represent a significant process affecting the biogeochemical cycling of
      forested ecosystems-particularly for temperate deciduous forests with distinct
      phenological seasons (or "phenoseasons"). Most studies on temperate deciduous
      forests aggregate seasonal throughfall fluxes to the leafed (growing) and
      leafless (dormant) periods, yet the phenological conditions controlling
      seasonality demand finer-scale demarcations that include the transitional
      phenoseasons (leaf senescence and emergence). To fill these gaps our study
      examines the washoff and leaching dynamics of Na(+), Mg(2+), K(+), Ca(2+), Cl(-),
      SO(4)(2-), and NO(3)(-) throughfall derived from bulk and sequentially sampled
      rain events across leafed, leafless and both transitional phenoseasons over a 3
      year period (2008-2010). As throughfall washoff and leached solute fluxes are
      also closely-coupled to rainfall conditions, we further examine the effects of
      storm characteristics on phenoseasonal washoff-dominated (Na(+) and Cl(-)) and
      leaching-dominated (K(+), Ca(2+), Mg(2+)) fluxes through intrastorm event
      comparison plots and factorial MANOVA. Highly significant differences in leached
      and washoff solute fluxes were found across meteorological conditions (p<0.001)
      nested within phenoseasonal divisions (p<0.00001). Phenoseasonal washoff Na(+)
      and Cl(-) fluxes seemed to be more closely related to leaf area; whereas,
      leaching flux and canopy exchange of all solutes to correspond more with major
      phenological changes (when the canopies tend to be most metabolically active).
      The greatest differences in leached Mg(2+), K(+), Ca(2+), and SO(4)(2-) fluxes
      were not between the full leafed and leafless phenoseasons (33-80% difference),
      but between the transitional periods (80 to 200 fold greater during leaf
      senescence than leaf emergence). Intrastorm average canopy NO(3)(-) leaching,
      however, ranged from low losses (1 MUmol(c)m(-2)h(-1)) to canopy uptake (-2
      MUmol(c)m(-2)h(-1)) during both transitional phenoseasons. K(+), Ca(2+), Mg(2+)
      were all markedly more exchangeable during senescence, with Ca(2+) and Mg(2+)
      being more tightly held by the canopy. Leaching rates and fluxes for all measured
      solutes were negligible to negative during emergence, except for K(+) and SO(4)(2
      ). Our results indicate that much of the variance in timing and magnitude of
      throughfall solute fluxes to forest soils within temperate deciduous ecosystems
      may be ascribed to phenologically-delineated seasons and storm conditions.

PMID- 22621812
TI  - Impairment of sexual function in rats with epilepsy.
AB  - INTRODUCTION: Epilepsy is a chronic disease that affects men and women of all
      ages, with different levels of severity. Many individuals with epilepsy also
      suffer from impairments in sexual function. However, it is difficult to
      differentiate between the impact of the disease and the impact of antiepileptic
      drugs on sexual function in human subjects. AIMS: To evaluate sexual behavior in
      adult male rats submitted to chronic pilocarpine-induced epilepsy. METHODS:
      First, non-epileptic rats were exposed to nine training sessions to acquire
      sexual experience, and their baseline sexual performance was evaluated. Then, the
      same rats were given pilocarpine to induce status epilepticus followed by chronic
      epilepsy. Once the animals had developed spontaneous recurrent seizures, their
      sexual behavior was evaluated during three sessions. MAIN OUTCOME MEASURES:
      Examine changes in latencies to first mount, intromission, and ejaculation, and
      the total number of mounts, intromissions, and ejaculations. RESULTS: All outcome
      measures related to sexual motivation and sexual performance were markedly
      impaired during chronic epilepsy compared with the baseline and the control
      group. CONCLUSION: These findings will aid in understanding the interaction
      between sexual behavior and epilepsy, as well as encouraging further experimental
      studies in human patients with epilepsy suffering from sexual dysfunction.

PMID- 22621813
TI  - [Prevalence of Trypanosoma cruzi infection and vertical transmission in Latin
      American pregnant women in a health area of Biscay].
AB  - OBJECTIVES: To estimate the prevalence of Trypanosoma cruzi infection, the
      epidemiological factors associated with it, and the risk of maternal-foetal
      transmission in pregnant women from endemic areas seen in the catchment area of
      Cruces Hospital (Basque Country, Spain). METHODS: Descriptive study. Diagnosis of
      T. cruzi infection in pregnant women and neonates by performing serological tests
      and parasitological diagnosis using PCR. Epidemiological survey and multivariate
      analysis to identify the risk factors associated with T. cruzi infection.
      RESULTS: A total of 158 women participated in the study between December 2008 and
      January 2010, with mean age of 28.5 (+/-5.3). Nineteen (12%) pregnant mothers
      were seropositive, of whom 16 (84.2%) came from Bolivia, with a prevalence, in
      this group, of 22.2%. Independent epidemiological risk factors associated with T.
      cruzi infection were a history of living in mud houses (OR: 4.62; 95%IC: 1.54
      13.87; P=.006) and knowledge of the vector (OR: 9.07; 95%IC: 1.91-43.11; P=.006).
      There was one newborn infected, which assumed a congenital transmission rate of
      5.8% CONCLUSIONS: On the basis of the high prevalence of T. cruzi infection
      detected in Latin-American pregnant women and the risk of vertical transmission,
      a screening program would be recommended, which would be fundamentally based on
      the identification of geographic origin and epidemiological variables.

PMID- 22621814
TI  - Withdrawal of antiepileptic drugs in young patients with cryptogenic focal
      epilepsies.
AB  - PURPOSE: The goal of the study was to assess the outcome of antiepileptic drug
      (AED) withdrawal in children and adolescents with cryptogenic focal epilepsies
      (CFE). METHODS: Medical records of consecutive patients with CFE from two
      referral hospitals were retrospectively evaluated over a nine-year period.
      Inclusion criteria were: (1) diagnosis of CFE according to the ILAE criteria, (2)
      less than 16 years of age at onset of epilepsy, (3) established clinical
      remission of at least two years before AED withdrawal, and (4) follow-up period
      of at least two years after withdrawal (or until seizure relapse in patients who
      relapsed). Time to seizure relapse and predictive factors were analyzed by
      survival methods. RESULTS: The cohort consisted of 52 patients (16 females, 36
      males). Relapse rate was 37.85%. Most relapses occurred during the first 12
      months after withdrawal. Univariate analyses indicated the following factors as
      significantly correlated with seizure recurrences: (1) female sex; (2) age at
      withdrawal of AED 14 years or higher; (3) abnormal EEG before withdrawal; and (4)
      abnormal EEG during and after AED withdrawal. Multivariate Cox regression
      analyses revealed that female sex, age at withdrawal of AED 14 years or higher;
      and abnormal EEG during and after withdrawal were significant independent
      predictive factors for seizure recurrences. CONCLUSION: The relapse rate in our
      cohort was similar to the most commonly reported overall rates for childhood
      onset epilepsy. Distinguishing variables-female sex, age at withdrawal greater
      than 14 years, and abnormal EEG - need to be considered when choosing and further
      following of eligible candidates for AED withdrawal.

PMID- 22621815
TI  - Prenatal retinoic acid improves lung vascularization and VEGF expression in CDH
      rat.
AB  - OBJECTIVE: We sought to investigate the effects of antenatal retinoic acid on the
      pulmonary vasculature and vascular endothelial growth factor (VEGF) and VEGF
      receptors (VEGFR) expression in a nitrofen-induced congenital diaphragmatic
      hernia (CDH) model. STUDY DESIGN: Rat fetuses were exposed to nitrofen at
      gestational day 9.5 and/or all-trans retinoic acid (ATRA) at gestational days
      18.5-20.5. We assessed lung growth, airway, and vascular morphometry. VEGF,
      VEGFR1, and VEGFR2 expression was analyzed by Western blotting and
      immunohistochemistry. Continuous data were analyzed by analysis of variance and
      Kruskal-Wallis test. RESULTS: CDH decreased lung to body weight ratio, increased
      mean linear intercept and mean transection length/airspace, and decreased mean
      airspace cord length. ATRA did not affect lung growth or morphometry. CDH
      increased proportional medial wall thickness of arterioles while ATRA reduced it.
      ATRA recovered expression of VEGF and receptors, which were reduced in CDH.
      CONCLUSION: Retinoic acid and VEGF may provide pathways for preventing pulmonary
      hypertension in CDH.

PMID- 22621816
TI  - The risk of diagnostic hysteroscopy in women with endometrial cancer.
AB  - OBJECTIVE: We sought to evaluate whether hysteroscopy in patients with
      endometrial cancer had an effect on disease stage or mortality. STUDY DESIGN:
      This was a retrospective cohort analysis of data linked between a registry of
      women diagnosed with endometrial cancer and physician billing data on
      hysteroscopy. RESULTS: A 99.8% match rate was obtained. Eighty-five percent of
      cases had complete data on staging. Of these 1972 cases, 672 (34.1%) had
      undergone hysteroscopy. There was no difference in stage III disease between the
      hysteroscopy (7.1%) vs no hysteroscopy (6.5%) group (P = .38). There was also no
      difference in death rates, 13.2% vs 15.2% (P = .25), or in the proportion of
      women dying of female genital organ cancer, 46.1% vs 42.1% (P = .53),
      respectively. CONCLUSION: Hysteroscopy is not associated with a higher rate of
      stage III disease or mortality. It allows for accurate diagnosis with direct
      visualization and biopsy, and should be considered a safe diagnostic tool.

PMID- 22621817
TI  - Chlamydial and gonococcal testing during pregnancy in the United States.
AB  - OBJECTIVE: The objective of the study was to estimate the rates of testing,
      prevalence, and follow-up testing for chlamydial and gonococcal infection in a
      nationally based population that is comparable with the US pregnant population in
      terms of age and race. STUDY DESIGN: We extracted laboratory results for
      1,293,423 pregnant women tested over a 3-year period. RESULTS: During pregnancy,
      59% (761,315 of 1,293,423) and 57% (730,796 of 1,293,423) of women were tested at
      least once for Chlamydia trachomatis or for Neisseria gonorrhoeae, respectively.
      Of those women tested, 3.5% (26,437 of 761,315) and 0.6% (4605 of 730,796) tested
      positive for chlamydial and gonococcal infection, respectively, at least once
      during pregnancy. Of those women who were initially positive for the given
      infection, 78% (16,039 of 20,489) and 76% (2610 of 3435) were retested, of whom
      6.0% (969 of 16,039) and 3.8% (100 of 2610) were positive on their last prenatal
      test for C trachomatis and N gonorrhoeae, respectively. CONCLUSION: Many pregnant
      women are not tested for C trachomatis and N gonorrhoeae despite recommendations
      to test. Follow-up testing to monitor the effectiveness of treatment is also not
      always performed.

PMID- 22621818
TI  - Effect of tetrabenazine on computerized dynamic posturography in Huntington
      disease patients.
AB  - BACKGROUND: Impairment in computerized dynamic posturography scores has been
      documented in Huntington disease patients. Tetrabenazine is approved to treat
      chorea in Huntington disease, but its effect on posturography scores, and balance
      in general, is unknown. MATERIALS AND METHODS: We designed a study to test
      computerized dynamic posturography performance while taking tetrabenazine and
      after stopping tetrabenazine for at least three days. RESULTS: 10 Huntington
      disease patients were studied both ON and OFF tetrabenazine. The composite score
      was statistically different between ON and OFF conditions and both conditions
      were significantly worse than reference scores. There was no significant
      difference between ON and OFF trials in the number of falls. A significant
      improvement on sensory orientation test conditions 3 (sway-referenced vision) and
      5 (sway-referenced motion of the support surface and eyes closed) was seen while
      ON tetrabenazine. Strategy scores 1-3 were also significantly different while ON
      tetrabenazine. CONCLUSION: These findings suggest that tetrabenazine aided
      patients in gating out of abnormal visual cues when other sensory modalities were
      available, as well as in gating out abnormal kinesthetic cues when visual cues
      were not available. It could not help with gating out of simultaneous abnormal
      visual and somatosensory cues. Thus, tetrabenazine can improve postural stability
      when one sensory modality is irrelevant, but this effect is not sustained when
      multiple abnormal sensory modalities are present. This is the first study
      supporting the use of any medicine to treat balance problems in Huntington
      disease.

PMID- 22621819
TI  - Healthcare utilization in patients with Parkinson's disease: a population-based
      analysis.
AB  - PURPOSE: To investigate factors associated with healthcare utilization and
      prescription drug use for Parkinson's disease (PD) patients and matched controls.
      METHODS: A retrospective matched-group design was adopted using administrative
      data from Manitoba, Canada. PD cases (N = 1469) were identified from diagnoses in
      hospital records and physician billing claims and matched to controls (N = 2938)
      on age, sex, and region of residence. Sixteen measures of healthcare utilization
      were examined over a six-year period using generalized linear models. RESULTS: PD
      cases had greater healthcare utilization than controls for almost all
      investigated services, with the exception of visits to non-neurological
      specialists and hospital use for non-mental disorder diagnoses. For controls,
      utilization of all forms of healthcare increased with age; for PD cases the
      relationship was weak, except for specialist visits, where an inverse
      relationship was observed. A rural region of residence was associated with a
      lower rate of seeing a specialist or any medical doctor, with a higher rate of
      hospitalization than for urban cases or controls. Comorbidity was strongly
      associated with healthcare use for both groups. Over the six-year study period
      significant differences in the trend were observed for mental disorder
      hospitalizations, hospital days, and physician visits. CONCLUSIONS: Factors
      associated with healthcare utilization in PD patients differ from those without
      PD. This information may help to identify and optimize healthcare services and
      associated costs for PD patients.

PMID- 22621820
TI  - The natural history of community-acquired pneumonia in COPD patients: a
      population database analysis.
AB  - BACKGROUND: Patients with Chronic Obstructive Pulmonary Disease (COPD) are at
      higher risk of developing Community-Acquired Pneumonia (CAP) than patients in the
      general population. However, no studies have been performed in general practice
      assessing longitudinal incidence rates for CAP in COPD patients or risk factors
      for pneumonia onset. METHODS: A cohort of COPD patients aged >= 45 years, was
      identified in the General Research Practice Database (GPRD) between 1996 and
      2005, and annual and 10-year incidence rates of CAP evaluated. A nested case
      control analysis was performed, comparing descriptors in COPD patients with and
      without CAP using conditional logistic regression generating odds ratios (OR) and
      95% confidence intervals (CI). RESULTS: The COPD cohort consisted of 40,414
      adults. During the observation period, 3149 patients (8%) experienced CAP,
      producing an incidence rate of 22.4 (95% CI 21.7-23.2) per 1000 person years. 92%
      of patients with pneumonia diagnosis had suffered only one episode. Multivariate
      modelling of pneumonia descriptors in COPD indicate that age over 65 years was
      significantly associated with increased risk of CAP. Other independent risk
      factors associated with CAP were co-morbidities including congestive heart
      failure (OR 1.4, 95% CI 1.2-1.6), and dementia (OR 2.6, 95%CI 1.9-3.). Prior
      severe COPD exacerbations requiring hospitalization (OR 2.7, 95% CI 2.3-3.2) and
      severe COPD requiring home oxygen or nebulised therapy (OR 1.4, 95% CI 1.1-1.6)
      were also significantly associated with risk of CAP. CONCLUSION: COPD patients
      presenting in general practice with specific co-morbidities, severe COPD, and age
      >65 years are at increased risk of CAP.

PMID- 22621821
TI  - Derivation and cardiomyocyte differentiation of induced pluripotent stem cells
      from heart failure patients.
AB  - AIMS: Myocardial cell replacement therapies are hampered by a paucity of sources
      for human cardiomyocytes and by the expected immune rejection of allogeneic cell
      grafts. The ability to derive patient-specific human-induced pluripotent stem
      cells (hiPSCs) may provide a solution to these challenges. We aimed to derive
      hiPSCs from heart failure (HF) patients, to induce their cardiomyocyte
      differentiation, to characterize the generated hiPSC-derived cardiomyocytes
      (hiPSC-CMs), and to evaluate their ability to integrate with pre-existing cardiac
      tissue. METHODS AND RESULTS: Dermal fibroblasts from two HF patients were
      reprogrammed by retroviral delivery of Oct4, Sox2, and Klf4 or by using an
      excisable polycistronic lentiviral vector. The resulting HF-hiPSCs displayed
      adequate reprogramming properties and could be induced to differentiate into
      cardiomyocytes with the same efficiency as control hiPSCs (derived from human
      foreskin fibroblasts). Gene expression and immunostaining studies confirmed the
      cardiomyocyte phenotype of the differentiating HF-hiPSC-CMs. Multi-electrode
      array recordings revealed the development of a functional cardiac syncytium and
      adequate chronotropic responses to adrenergic and cholinergic stimulation. Next,
      functional integration and synchronized electrical activities were demonstrated
      between hiPSC-CMs and neonatal rat cardiomyocytes in co-culture studies. Finally,
      in vivo transplantation studies in the rat heart revealed the ability of the HF
      hiPSC-CMs to engraft, survive, and structurally integrate with host
      cardiomyocytes. CONCLUSIONS: Human-induced pluripotent stem cells can be
      established from patients with advanced heart failure and coaxed to differentiate
      into cardiomyocytes, which can integrate with host cardiac tissue. This novel
      source for patient-specific heart cells may bring a unique value to the emerging
      field of cardiac regenerative medicine.

PMID- 22621822
TI  - [Percutaneous Image-guided cryoablation for localized bone plasmacytoma
      treatment].
AB  - Bone plasmacytoma (BP) occurs in most patients with multiple myeloma and is
      highly disabling. Radiotherapy is the primary treatment modality for BP and,
      although local control rates are excellent, several weeks are needed before the
      treatment is completed and for patients to note significant pain relief. Over the
      past decade, percutaneous image-guided cryoablation has emerged as a safe and
      effective alternative in the management of localized bone metastasis in solid
      tumours. In this report the author's show that a localized BP was successfully
      treated using this procedure. Furthermore, some of the most relevant potential
      advantages that makes this procedure more attractive than other alternative
      techniques are highlighted.

PMID- 22621823
TI  - [Cockett's syndrome, May-Thurner syndrome, or iliac vein compression syndrome].
AB  - Iliac vein compression syndrome (also known as May-Thurner syndrome or Cockett's
      syndrome) is a rare clinical entity in which the left common iliac vein is
      compressed when it passes between the right common iliac artery and the spine.
      The sustained compression and trauma caused by the pulsatile force of the artery
      on the vein damage the intima and lead to the formation of membranes or bands in
      the vascular lumen that hinder or obstruct the flow of blood in the vein,
      favoring thrombus formation. The current treatment strategy of choice is
      endovascular vein patch angioplasty and stenting with the aim of improving the
      caliber of the lumen and enabling normal venous drainage. We present two cases of
      May-Thurner syndrome and review the clinical and CT findings.

PMID- 22621824
TI  - [Ethical aspects of research in radiology].
AB  - Clinical research on human beings is essential for progress in medicine; however,
      it is also essential to safeguard research subjects' autonomy, dignity, and
      rights. Diverse documents have been developed in consensus to address these
      issues: some of the most relevant are the Nuremberg Code, the Helsinki
      Declaration, and the Oviedo Convention. In addition to being familiar with these
      fundamental documents, all radiologists who conduct research should know about
      Ethics Committees and consult them about the methodology of their studies, which
      must fulfill the conditions stipulated in the above-mentioned guidelines as well
      as in the legislation in force.

PMID- 22621825
TI  - Estimating the cost of serious injurious falls in a Canadian acute care hospital.
AB  - Falls represent 40 per cent of hospital accidents, and consequences range from
      none to serious injuries. The purpose of this study was to estimate the average
      hospital cost and length of stay (LOS) associated with serious injurious falls in
      an acute care hospital. We used data from risk management and case costing
      databases to identify cost associated with a serious injury after an in-hospital
      fall. Thirty-seven injured patients were matched with 2,113 controls by the most
      responsible medical diagnosis, age, and gender. Cost and LOS were compared using
      t-tests and multivariate regression. Average costs for seriously injured fallers
      and non-faller controls were CAD$44,203 and CAD$13,507, while LOS was 45 and 11
      days respectively. Hospital cost for a seriously injured faller was $30,696 (95%
      CI: $25,158 - $36,781) greater than the cost for a non-faller. Hospital managers
      have a leading role in creating system-wide falls prevention programs and
      reducing hospital costs.

PMID- 22621826
TI  - BK-virus infections: a literature review.
AB  - BK-virus is a very common polyomavirus in the global population, similar to the
      JC-virus responsible for Progressive Multifocal Leukoencephalopathy. BK-virus
      infections are an important diagnostic and therapeutic challenge in immuno
      compromised patients, including: bone marrow transplant pediatric recipients in
      whom it may cause hemorrhagic cystitis, renal transplant recipients in whom it
      may cause interstitial nephropathy leading to graft loss, and in HIV infected
      patients in whom it may cause some types of encephalitis. Indeed, this poorly
      documented virus is responsible for infections with various clinical profiles,
      probably under-diagnosed, but could also be involved in the genesis of some
      cancers, especially cervix and prostate cancer. We reviewed the latest published
      data on this virus focusing on its possible pro-oncogenic properties. We also
      listed the diseases in which it is involved, with an emphasis on rare and
      insufficiently investigated entities. Finally, we studied the new tools available
      for diagnosis and treatment, and their importance in current practice.

PMID- 22621828
TI  - Pneumococcal vaccines WHO position paper - 2012 - recommendations.
AB  - This article presents the World Health Organization (WHO) recommendations on the
      use of pneumococcal vaccines excerpted from the Pneumococcal vaccines WHO
      position paper - 2012 recently published in the Weekly Epidemiological Record.
      The current document replaces the position paper on the use 7-valent pneumococcal
      conjugate vaccine published in 2007. Incorporating the most recent developments
      in the field of pneumococcal vaccines this position paper focuses on the
      currently available 10-valent and 13-valent conjugate vaccines and their
      introduction and use in national immunization programmes. It also deals with the
      23-valent polysaccharide vaccine, though in less detail than provided in the
      April 2008 position paper which remains valid. Footnotes to this paper provide a
      number of core references including references to grading tables that assess the
      quality of scientific evidence for a few key conclusions. 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 worldwide. This paper reflects the recommendations of the WHO's
      Strategic Advisory Group of Experts (SAGE) on immunization. Recommendations on
      the use of pneumococcal vaccines were discussed by SAGE at its meetings in
      November 2006 (conjugate vaccine) and April 2008 (polysaccharide vaccine) and
      most recently in November 2011. Evidence presented at these meetings can be
      accessed at http://www.who.int/immunization/sage/previous/en/index.html.

PMID- 22621827
TI  - Update on counterfeit antibiotics worldwide; public health risks.
AB  - Antibiotics are the most counterfeited medicines and account for 28% of global
      counterfeit medicines. Counterfeit antibiotics are estimated at 5% of the global
      antibiotic market. No area in the world seems to be spared from counterfeiting of
      antibiotics. However, these are rare in developed countries, whereas the strong
      demand for antibiotics in emerging countries creates a highly attractive market
      for counterfeiters. Thus, 78% of counterfeit antibiotics come from South-East
      Asia and their destination is mainly emerging countries (South-East Asia: 44%;
      sub-Saharan Africa: 30%; Europe, North America: 9%; others: 16%). Counterfeit
      antibiotics are antibiotics that have been commonly used for years (beta-lactams:
      50%; quinolones: 12%; macrolides, lincosamides, and synergistins: 1%; cyclins:
      7%; others: 20%). The main counterfeit formulations (77%) concern oral
      administration (tablets, syrup, capsules) whereas injected drugs account for only
      17% of counterfeit formulations, and eye drops and ointments 6%. The kind of
      counterfeiting for antibiotics is similar to that of other drugs (no active
      ingredients: 43%; bad quality: 24%; insufficient quantity of active ingredients:
      21%; wrong active ingredients: 7%; counterfeit packaging: 5%). Beyond the harmful
      effects for patients, counterfeit medicines favor the emergence of bacterial
      resistance with a worldwide impact. Great efforts have been made to fight global
      counterfeiting of medicines since 1985.

PMID- 22621829
TI  - Effect of hCG priming on embryonic development of immature oocytes collected from
      unstimulated women with polycystic ovarian syndrome.
AB  - BACKGROUND: The effect of hCG priming on oocyte maturation and subsequently
      outcome in IVM cycles has remained a debated issue. A randomized controlled study
      was performed to investigate whether or not hCG priming prior to oocyte
      aspiration can improve the developmental competence of immature oocytes from
      unstimulated ovaries in women with polycystic ovarian syndrome (PCOS). METHODS:
      Eighty two patients with PCOS underwent IVM cycles. Each patient was randomly
      assigned to the hCG-primed (10,000 IU) or non-primed groups 36-38 hours before
      oocyte retrieval depending on the computerized random table. After the oocytes
      had in vitro matured, fertilization, culture and embryo transfer were performed.
      RESULTS: The average number of cumulus-oocyte complexes (COCs) recovered was
      13.80 and 14.35 in the hCG-primed and non-primed groups, respectively (p>0.05).
      The maturation rate of COCs was significantly improved in the hCG-primed group
      (55.43% vs. 42.29%; p<0.05). The fertilization and cleavage rates were comparable
      between the groups. The hCG-primed and non-primed groups did not differ with
      respect to the clinical pregnancy (37.50% vs. 50.00%), live birth (22.50% vs.
      30.95%), and implantation rates (32.86% vs. 32.56%). The pregnancy losses was 6
      (40.00%) of 15 clinical pregnancies in the hCG-primed group, and 8 (38.10%) of 21
      clinical pregnancies in the non-primed group. CONCLUSIONS: While a significant
      improvement in the nuclear maturation rate of immature oocytes was observed in
      hCG-primed IVM cycles with PCOS patients, the use of hCG prior to oocyte
      retrieval did not improve the subsequent embryo developmental competence. The
      high rate of pregnancy loss in IVM cycles should receive more attention.

PMID- 22621830
TI  - [Why do users of a primary care center request a change of physician?].

PMID- 22621831
TI  - Total talar fracture - long-term results of internal fixation of talar fractures.
      A multicentric study of 114 cases.
AB  - INTRODUCTION: Displaced talar neck and body fractures are rare and challenging
      for the surgeon. Results are often disappointing due to inadequate reduction or
      internal fixation and high rates of osteoarthritis and osteonecrosis. Very few
      published series describe the long-term results after internal fixation of talar
      factures. One of the goals of the 2011 SOO meeting symposium was to specifically
      evaluate the long-term results after internal fixation of talar fractures. This
      study included only central fractures. MATERIAL AND METHODS: We reviewed the
      results of 114 central talar fractures that had been treated by internal fixation
      between 1982 and 2006 in nine hospitals in the Western part of France. The
      clinical and radiological follow-up was 111 months on average. All the patients
      with a radiological assessment had at least 5 years of follow-up. RESULTS: Poor
      reduction was apparent in 33% of cases. The average Kitaoka score was 70/100,
      which corresponds to an average functional level. At the last follow-up
      evaluation, 34% of cases had osteonecrosis and 74% had peritalar osteoarthritis.
      Secondary fusion was required in 25% of cases with an average follow-up of 24
      months. DISCUSSION: The complication rate for talar fractures was high, mostly
      due to osteonecrosis and osteoarthritis; these conditions had an impact on the
      final outcome. The outcome could be improved by better evaluating these fractures
      with a CT scan, developing dual surgical approaches to best preserve the bone
      vascular supply and achieve better reduction, and improving the internal fixation
      hardware, especially the use of plates for comminuted fractures.

PMID- 22621832
TI  - Comparison of open preperitoneal and Lichtenstein repair for inguinal hernia
      repair: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: The aim of this article was to compare the outcomes of the open
      preperitoneal approaches and the Lichtenstein technique in the repair of inguinal
      hernias. METHODS: A systematic literature review was undertaken to identify
      studies comparing the outcomes of open preperitoneal and Lichtenstein techniques
      in the repair of inguinal hernias. RESULTS: The present meta-analysis pooled the
      effects of outcomes of a total of 2,860 patients enrolled into 10 randomized
      controlled trials and 2 comparative studies. The preperitoneal technique was
      associated with a lesser incidence of recurrence (odds ratio = .51; 95%
      confidence interval, .28-.92). However, statistically there was no difference in
      the incidence of chronic pain, hematoma, wound infection, testicular problem,
      urinary problem, numbness, inguinal parenthesis, and operative time. CONCLUSIONS:
      The open preperitoneal approach is a feasible alternative for the standard
      Lichtenstein procedure with similar complication rates and potentially less
      postoperative recurrence.

PMID- 22621833
TI  - Role models and mentors in surgery.
AB  - BACKGROUND: A number of studies have highlighted the importance of positive role
      models and mentors in influencing medical students' ultimate career decisions.
      This article sought to review the relevant literature in relation to mentors and
      role models in surgery. DATA SOURCES: A comprehensive PubMed search of the
      literature on the subject of role models and mentors was performed using the
      following keywords: "Mentors," "Mentorship," and "Role Models" alone and in
      conjunction with the words "medicine" and "surgery." CONCLUSIONS: This article
      defines the terms role model and mentor and highlights the differences between
      these. It identifies the importance of early intervention in medical students'
      careers by surgeons and the possibility of junior doctors acting as mentors.
      Formal mentoring programs appear to be associated with greater satisfaction among
      surgical trainees regarding mentorship. In addition, this review serves to show
      the potential approaches to developing mentorship and role models in surgery.

PMID- 22621834
TI  - The perioperative management of patients with coronary artery stents: surveying
      the clinical stakeholders and arriving at a consensus regarding optimal care.
AB  - BACKGROUND: The perioperative management of patients with a coronary artery stent
      is a major patient safety issue currently confronting clinicians. Surgery on a
      patient on antiplatelet therapy creates the following dilemma: is it better to
      withdraw the drugs and reduce the hemorrhagic risk or to maintain them and reduce
      the risk of a myocardial ischemic event? METHODS: An electronic survey was used
      to sample a cross-section of local clinicians regarding the perioperative
      management of patients with an indwelling coronary artery stent. The reiterative
      Consensus-Oriented Decision-Making model was applied by an institutional task
      force with representation from anesthesiology, cardiology, primary care medicine,
      and surgery. RESULTS: Significant disagreement existed among the
      multidisciplinary survey respondents regarding various aspects of the
      perioperative management of patients with indwelling coronary artery stents.
      CONCLUSIONS: We clarified the perioperative risk factors for coronary stent
      thrombosis and an alternate process for immediate access to a cardiac
      catheterization laboratory at our institution.

PMID- 22621835
TI  - [Ultrasound-guided infraclavicular axillary vein cannulation].
AB  - BACKGROUND AND OBJECTIVE: Percutaneous central venous cannulation is a
      challenging procedure. Traditionally, an external landmark technique has been
      used to identify puncture site. We wanted to evaluate an ultrasound-guided
      technique for the axillary vein cannulation, looking specifically at the ease of
      use, success rate and decreased complications. METHODS: Sixty consecutive
      surgical patients scheduled for central venous catheter placement were
      registered. An ultrasound scanner made for guiding an in plane puncture of
      axillary vein was used. After locating the vessels, an echo-guided sterile
      procedure was performed to cannulate the vein. RESULTS: Cannulation was
      successful in all patients, and there were no complications during insertion of
      the catheters. Both axillary veins were cannulated, and the vein was punctured
      successfully at first attempt in 95% of the patients. The median time from the
      start of the first puncture (of the skin) until the aspiration of blood was 15 (7
      135) seconds. CONCLUSION: This ultrasound-guided technique for inserting central
      venous catheters in axillary vein was easy to apply. This procedure could
      increase precision and safety in patients undergoing axillary vein cannulation.

PMID- 22621836
TI  - Performance and quality of life outcomes for T4 laryngeal cancer patients treated
      with induction chemotherapy followed by chemoradiotherapy.
AB  - Organ-sparing approaches with chemoradiotherapy are often used in the treatment
      of patients with laryngeal cancer, and the oncologic outcomes of these patients
      are similar to patients who undergo laryngectomy. However, chemoradiotherapy for
      laryngeal cancer patients with large or locally-invasive (T4) tumors has been
      more slowly incorporated due to concern for poor post-treatment function of the
      preserved larynx. Here, we characterize acute and long-term performance and
      quality-of-life (QOL) outcomes of T4 laryngeal cancer patients treated with
      induction chemotherapy followed by combined chemoradiotherapy. Using several
      validated metrics, we find patients experience a decline in most measures of
      performance and QOL during and immediately following treatment. However, the
      majority of patients improve to baseline over varying lengths of time following
      completion of treatment, and many go on to exceed pre-treatment levels of
      function. Gender, race, alcohol, and tobacco usage were found to be associated
      with differences in performance and QOL scores across time points. This study
      suggests that patients with advanced laryngeal tumors who historically had been
      considered poor candidates for organ-sparing treatment are able to return to, and
      in many cases exceed pre-treatment performance and QOL following induction
      chemotherapy and combined chemoradiotherapy.

PMID- 22621837
TI  - How much are we willing to pay to prevent a fall? Cost-effectiveness of a
      multifactorial falls prevention program for community-dwelling older adults.
AB  - This study examined the cost-effectiveness of a multifactorial falls prevention
      program and estimated the trade-off between the extra costs of such a program and
      the additional reduction of unintentional falls. Cost-effectiveness was evaluated
      using the traditional incremental cost-effectiveness ratio (ICER) and the net
      benefit regression framework (NBRF). Using the NBRF, decision making was
      formalized by incorporating values of willingness to pay (WTP) a priori. The
      results failed to provide evidence that a multifactorial falls prevention program
      was cost-effective. Participant adherence to recommendations ranged from low
      (41.3%), to moderate (21.1%), to high (37.6%). A future challenge is to
      understand more clearly the relationship between the community-dwelling older
      adult, potentially modifiable risks for falls, adherence to multifactorial risk
      factor recommendations, costs, and resulting effects of falls prevention
      practices. Future economic evaluations of falls prevention interventions remain
      necessary and should consider the NBRF so that regression tools can facilitate
      cost-effectiveness analysis.

PMID- 22621838
TI  - Assessment of the mutagenic, recombinagenic and carcinogenic potential of
      orlistat in somatic cells of Drosophila melanogaster.
AB  - In this study the mutagenic, recombinagenic, carcinogenic and anticarcinogenic
      potential of orlistat was assessed using the somatic mutation and recombination
      test (SMART) and the epithelial tumor detection test (wts). The experiments were
      conducted on Drosophila melanogaster. In the assessment using SMART, larvae,
      descendants from the standard (ST) cross and the high bioactivation (HB) cross,
      were treated chronically with three orlistat concentrations. The results revealed
      a recombinagenic effect, associated with orlistat, in the descendants of the HB
      cross, at all three levels of concentration. Homologous recombination can
      function as a determinant at different stages of carcinogenesis. For
      verification, larvae from the wts test, descendants of the wts/TM3 virgin female
      and mwh/mwh male cross, were treated with the same three orlistat concentrations
      separately and in association with mitomicin C (0.1mM). The results did not,
      however, provide evidence that orlistat has carcinogenic potential nor was it
      associated with the reduction of tumors induced by mitomicin C in D.
      melanogaster.

PMID- 22621839
TI  - Optimization of sampling parameters for collection and preconcentration of
      alveolar air by needle traps.
AB  - The approach for breath-VOCs' collection and preconcentration by applying needle
      traps was developed and optimized. The alveolar air was collected from only a few
      exhalations under visual control of expired CO(2) into a large gas-tight glass
      syringe and then warmed up to 45  degrees C for a short time to avoid
      condensation. Subsequently, a specially constructed sampling device equipped with
      Bronkhorst(r) electronic flow controllers was used for automated adsorption. This
      sampling device allows time-saving collection of expired/inspired air in parallel
      onto three different needle traps as well as improvement of sensitivity and
      reproducibility of NT-GC-MS analysis by collection of relatively large (up to 150
      ml) volume of exhaled breath. It was shown that the collection of alveolar air
      derived from only a few exhalations into a large syringe followed by automated
      adsorption on needle traps yields better results than manual sorption by up/down
      cycles with a 1 ml syringe, mostly due to avoided condensation and electronically
      controlled stable sample flow rate. The optimal profile and composition of needle
      traps consists of 2 cm Carbopack X and 1 cm Carboxen 1000, allowing highly
      efficient VOCs' enrichment, while injection by a fast expansive flow technique
      requires no modifications in instrumentation and fully automated GC-MS analysis
      can be performed with a commercially available autosampler. This optimized
      analytical procedure considerably facilitates the collection and enrichment of
      alveolar air, and is therefore suitable for application at the bedside of
      critically ill patients in an intensive care unit. Due to its simplicity it can
      replace the time-consuming sampling of sufficient breath volume by numerous
      up/down cycles with a 1 ml syringe.

PMID- 22621840
TI  - Synthesis and biological activity of novel mycophenolic acid conjugates
      containing nitro-acridine/acridone derivatives.
AB  - Hybrid pharmacophore anti-proliferative compounds, comprised of mycophenolic acid
      (MPA) and 1-nitroacridine/4-nitroacridone derivative have been synthesized and
      evaluated as inhibitors of five different leukemia cell lines (Jurkat, Molt-4, HL
      60, CCRF-CEM, L1210) and human peripheral blood mononuclear cells from healthy
      donors. These conjugates possess different length of the linker between MPA and
      heterocyclic units. The type of heterocyclic part influenced their cytotoxic and
      anti-proliferative properties. Coupling of MPA 1 with 9-(omega-aminoalkyl)amino-1
      nitroacridines 2 and 1-[(omega-aminoalkyl)-4-nitro-9(10H)]-acridones 3 was
      tested. Although all tested conjugates were active, compounds 4a-e exhibited the
      highest potency. Preliminary experiments with GMP suggested that the tested
      compounds acted as IMPDH inhibitors.

PMID- 22621841
TI  - Synthesis and biological evaluation of 4-alkoxy-6,9-dichloro[1,2,4]triazolo[4,3
      a]quinoxalines as inhibitors of TNF-alpha and IL-6.
AB  - An efficient synthetic method for previously unattainable 4-alkoxy-6,9
      dichloro[1,2,4]triazolo[4,3-a]quinoxalines has been established. Reactions
      between 5,8-dichloro-2,3-dicyanoquinoxaline and alcohols in the presence of
      triethylamine led to 3-alkoxy-5,8-dichloro-2-cyanoquinoxalines in high to
      quantitative yields. These compounds were treated with hydrazine giving 3-alkoxy
      5,8-dichloro-2-hydrazinoquinoxalines in near quantitative yields, that reacted
      with triethyl orthoformate to provide the title compounds in high yields. The
      molecular structure of a member of this family of compounds: 6,9-dichloro-4
      ethoxy[1,2,4]triazolo[4,3-a]quinoxaline, was determined by X-ray crystallography.
      The series of compounds synthesized were evaluated for their potential anti
      inflammatory activity as inhibitors of the pro-inflammatory cytokines TNF-alpha
      and IL-6. Compounds 8e, 8a, 8b and 8g presented simultaneously good levels of
      inhibition of both cytokines being compound 8e the most concomitantly potent one.
      Compounds 8d, 8f and 8h specifically inhibited IL-6 with no significant
      inhibition of TNF-alpha. Compound 8c was not significantly active upon TNF-alpha,
      and showed no activity upon IL-6.

PMID- 22621842
TI  - Cancer incidence in Nigeria: a report from population-based cancer registries.
AB  - INTRODUCTION: Cancer has become a major source of morbidity and mortality
      globally. Despite the threat that cancer poses to public health in sub-Saharan
      Africa (SSA), few countries in this region have data on cancer incidence. In this
      paper, we present estimates of cancer incidence in Nigeria based on data from 2
      population-based cancer registries (PBCR) that are part of the Nigerian national
      cancer registry program. MATERIALS AND METHODS: We analyzed data from 2
      population based cancer registries in Nigeria, the Ibadan Population Based Cancer
      Registry (IBCR) and the Abuja Population Based Cancer Registry (ABCR) covering a
      2 year period 2009-2010. Data are reported by registry, gender and in age groups.
      We present data on the age specific incidence rates of all invasive cancers and
      report age standardized rates of the most common cancers stratified by gender in
      both registries. RESULTS: The age standardized incidence rate for all invasive
      cancers from the IBCR was 66.4 per 100000 men and 130.6 per 100000 women. In ABCR
      it was 58.3 per 100000 for men and 138.6 per 100000 for women. A total of 3393
      cancer cases were reported by the IBCR. Of these cases, 34% (1155) were seen
      among males and 66% (2238) in females. In Abuja over the same period, 1128
      invasive cancers were reported. 33.6% (389) of these cases were in males and
      66.4% (768) in females. Mean age of diagnosis of all cancers in men for Ibadan
      and Abuja were 51.1 and 49.9 years respectively. For women, mean age of diagnosis
      of all cancers in Ibadan and Abuja were 49.1 and 45.4 respectively. Breast and
      cervical cancer were the commonest cancers among women and prostate cancer the
      most common among men. Breast cancer age standardized incidence rate (ASR) at the
      IBCR was 52.0 per 100000 in IBCR and 64.6 per 100000 in ABCR. Cervical cancer ASR
      at the IBCR was 36.0 per 100000 and 30.3 per 100000 at the ABCR. The observed
      differences in incidence rates of breast, cervical and prostate cancer between
      Ibadan and Abuja, were not statistically significant. CONCLUSION: Cancer
      incidence data from two population based cancer registries in Nigeria suggests
      substantial increase in incidence of breast cancer in recent times. This paper
      highlights the need for high quality regional cancer registries in Nigeria and
      other SSA countries.

PMID- 22621843
TI  - Predictors of oral contraceptive use among teenaged girls in southeastern
      Hungary.
AB  - OBJECTIVE: To assess the main determinants of oral contraceptive (OC) use among
      teenaged girls in southeastern Hungary. METHODS: A questionnaire was self
      administered by 332 participants aged 14 to 19 years seen at the Contraception
      Outpatient Clinic for Teenagers located in the Department of the Obstetrics and
      Gynecology of the University of Szeged from May 1, 2005, to March 31, 2006.
      RESULTS: Approximately half of the respondents (48.2%) used OCs, and only 21.9%
      of the OC users considered OC cost unimportant (vs 59% of the non-OC users). A
      considerable proportion in each group knew little about the fertile period of a
      menstrual cycle (43.1% vs 46.5%) and had an insufficient knowledge of the
      recommendations regarding pill use (66.6% vs 77.9%). Most (76.2%) of the
      participants intended to use OCs in the future. Intending to use OCs was strongly
      associated with the prevention of menstrual disorders (adjusted odds ratio [AOR],
      4.73; 95% confidence interval [CI], 2.4-10.5) and the opinion that OCs did not
      interfere with sex life (AOR, 2.55; 95% CI, 1.3-5.1). CONCLUSION: The results
      demonstrate that the knowledge of teenaged girls concerning the correct use of
      OCs and the differences in fertility during the menstrual cycle is often
      inadequate and should be improved.

PMID- 22621844
TI  - Let it snow! Let it snow! Let it snow! Estimating cocaine production using a
      novel dataset based on reported seizures of laboratories in Colombia.
AB  - BACKGROUND: Data on the cocaine market appear inconsistent, as they tend to show
      declining prices vis-a-vis steady or increasing demand and a declining supply.
      This paper proposes an explanation for this trend by providing evidence of an
      under-estimation of the supply of cocaine. METHODS: We propose a conservative
      estimate of cocaine production in Colombia for 2008, using data based on all
      reported seizures from 328 laboratories made by the counteracting organisations
      operating within the Colombian territory. RESULTS: Our conservative estimate of
      935 tons from the seized laboratories is at least twice the estimate declared in
      official statistics of 295-450 tons. We are careful to keep all variables to
      their minimum boundary values. Our methodology could prove to be a useful tool,
      especially if used in parallel with the standard tools. Moreover, its
      characteristics (affordability, ease of use and potential for worldwide adoption)
      make it a powerful instrument to counteract cocaine production.

PMID- 22621845
TI  - [A new index to evaluate arterial ageing independently of arterial blood
      pressure: pOpscore((r))].
AB  - AIM: Pulse wave velocity does not correlate to age in the upper limb but in the
      aorta and lower limb. We studied the link between ageing and pulse wave transit
      time (PWtt) indexes at the toe and finger. PATIENTS AND METHODS: Measurements
      were performed in 300 patients in occupational medicine and primary care after
      5minutes supine rest using the device studied (pOpmetre((r)), Axelife SAS,
      France). It measures transit time between R-ECG and finger or toe pulse signal
      (ttf or ttt respectively). We define as follows three indexes: difference between
      transit times: Dtf=ttt-ttf; pulse wave velocity PWVft=k*subjects height/Dtf
      (m/s); and the pOpscore((r)) as the ratio of toe PWV/fingerPWV. RESULTS: Of the
      300 tested patients, 147 were analysed using univariate correlation: age (P<10(
      4)), SBP (P<10(-4)), DBP (P<0.02) and BMI (P<0.04) correlated to Dtf, PWVtf and
      pOpscore((r)). Using stepwise regression analysis with Age, BMI, SBP, DBP, MBP:
      Dtf was dependent with age (P<10(-4)) and SBP (P<0.01); PWVtf with age
      (P<0.0001), SBP (P<0.01) and DBP (P<0.05); pOpscore((r)) was dependent only to
      age (P<10(-4)). CONCLUSION: In this study, in contrast with the other vascular
      indexes studied dependent to age and blood pressure, pOpscore((r)) was dependent
      only to ageing. pOpmetre((r)) is a promising technique for routine determination
      of arterial stiffness and pOpscore((r)) appears to be appropriate to study the
      structural vascular ageing in outpatient.

PMID- 22621846
TI  - [Very late bare-metal stent thrombosis 10 years after the implantation: a case
      report].
AB  - Very late thrombosis occurring after bare-metal stent (BMS) implantation is a
      rare complication. It differs from very late thrombosis of drug-eluting stents in
      terms of both frequency and pathophysiological mechanism. We report a case of
      very late stent thrombosis of a bare-metal stent 10 years after his implantation
      for treatment of a myocardial infarction. The patient had a new acute coronary
      syndrome without persistent ST-segment elevation related to bare-metal stent
      thrombosis. He was treated by thrombo-aspiration and implantation of a new bare
      metal stent.

PMID- 22621847
TI  - [Impact of periodontal disease on arterial pressure in diabetic mice].
AB  - Diabetes-driven cardiovascular diseases represent a high challenge for developed
      countries. Periodontal disease is strictly linked to the aforementioned diseases,
      due to its Gram negative-driven inflammation. Thus, we investigated the effects
      of periodontal disease on arterial pressure during the development of diabetes in
      mice. To this aim, C57BL/6 female mice were colonized with pathogens of
      periodontal tissue (Porphyromonas gingivalis, Prevotella intermedia and
      Fusobacterium nucleatum) for 1month, whereas another group of mice did not
      undergo the colonization. Subsequently, all mice were fed a high-fat carbohydrate
      free diet for 3months. Then, arterial pressure was measured in vivo and a
      tomodensitometric analysis of mandibles was realized as well. Our results show
      increased mandibular bone-loss induced by colonization with periopathogens. In
      addition, periodontal infection augmented glucose-intolerance and systolic and
      diastolic arterial pressure, parameters already known to be affected by a fat
      diet. In conclusion, we show here that periodontal disease amplifies metabolic
      troubles and deregulates arterial pressure, emerging as a new axis of metabolic
      investigation.

PMID- 22621848
TI  - [Role of multidetector CT scan in the diagnosis of congenital coronary artery
      anomalies with inter-aortopulmonary course: about two cases and literature
      review].
AB  - Coronary anomalies are a rare entity. The gold standard remains the coronary
      angiogram. However, the identification of the origin and the course of aberrant
      coronary arteries using angiography may be difficult. We report two cases
      regarding two patients who underwent coronary angiography in order to evaluate
      coronary heart disease. In the first case, angiography has shown a left anterior
      descending artery (LAD) originating from the right anterior sinus. A
      multidetector CT scan (MDCT) showed an inter-aortopulmonary course of the LAD. In
      the second case, selective catheterization of the right coronary artery could not
      be done. A MDCT scan was performed. An abnormal origin of the right coronary
      artery was detected. It originates from the left sinus with a separate ostium of
      the left main coronary artery. This artery had an inter-aortopulmonary course.
      The 64 MDCT scan can be useful as a complementary tool for the diagnosis of
      coronary artery anomalies. Detection of the inter-aortopulmonary course is
      essential, since this situation will require surgical treatment to avoid sudden
      cardiac death. 

PMID- 22621849
TI  - [Aortic dissection spread to the renal arteries: role of renal volumetry after
      angioplasty].
AB  - OBJECTIVE: Type A or B aortic dissection can extend to renal arteries, causing a
      renal ischemia which treatment is usually endovascular. The aim of our study is
      to show the interest of the renal volumetry in the follow-up of these patients.
      PATIENTS AND METHODS: Twenty-two patients (16 men, mean age 63.4+/-11.8years, BMI
      25.2+/-3.4kg/m(2)) with a type A or B aortic dissection spread to one or to both
      renal arteries and followed at Grenoble university hospital were consecutively
      included. All patients underwent renal angiography with aorto-renal pressure
      gradients measurements and follow-up by renal volumetry (scanner Siemens((r))). A
      renal ischemia was defined by a decrease of 20% or more of the volumetry.
      RESULTS: Sixteen patients (73%) were hypertensive before the aortic dissection
      among which ten (62%) were treated. Eight patients (36%) have a significant renal
      pressure gradient among which five (62%) underwent renal endovascular therapy.
      The renal volumetry of these five patients remained unchanged while six of 17
      patients (36%) without angioplasty have a decreasing volumetry. CONCLUSION: Renal
      volumetry appeared an effective and attractive option for the follow-up of the
      patients with aortic dissection spread to the renal arteries. These results
      should be taken into account to put the indication of an endovascular treatment.

PMID- 22621850
TI  - [A cardiac rhabdomyome evoking the antenatal diagnosis of a Bourneville's
      tuberous sclerosis].
AB  - Rare hereditary affection, the Bourneville's tuberous sclerosis (BTS) is an
      autosomal dominant inherited phakomatosis. Rhabdomyomes are the most frequent
      cardiac tumors in children and infants, they are one of the most premature modes
      of revelation of the STB. They sometimes allow to envisage the diagnosis in
      antenatal period at the same time as the genetic and neurological explorations.
      We report the diagnosis of a fetal BTS evoked by the antenatal discovery of a
      cardiac rhabdomyome. The antenatal cerebral explorations, realized by magnetic
      resonance imagery (MRI), put evidence cerebral localisations confirming the
      diagnosis. 

PMID- 22621851
TI  - [A new, spontaneous method for assessing sympathetic baroreflex function in
      humans].
AB  - In humans, assessment of the sympathetic component of the arterial baroreceptor
      reflex (sBRS) is usually based on microneurographic recordings of muscle
      sympathetic nerve activity (MSNA), while inducing reflex changes with intravenous
      administration of vasoactive drugs (modified Oxford method). This method has
      several limitations, among which its poor temporal resolution. Some studies have
      proposed alternative methods by using spontaneous changes in arterial pressure
      (AP) and MSNA, usually collected under baroreflex closed-loop conditions (AP
      alters MSNA while MSNA alters AP), which makes the results difficult to
      interpret. In rats, a method has been developed and validated (Kanbar et al.,
      2007 [1]), which uses oscillations of renal SNA at the frequency of the heart
      beat. At this frequency, the baroreflex operates under open-loop conditions
      because of the low-pass filter properties of the resistance vasculature. The goal
      of the present study was to examine whether this method is applicable in humans.
      Data were previously collected by Gujic et al. (2007) [2]. Briefly, MSNA and AP
      were recorded in 16 young healthy subjects during a 5-minute baseline resting
      period then during a modified Oxford test (sodium nitroprusside and phenylephrine
      administrations). Using the 5-minute baseline recordings, spontaneous sBRS was
      assessed through empirical mode decomposition over consecutive 20-second periods.
      Spontaneous sBRS was significantly related to pharmacological sBRS (R=0.67, n=16,
      P=0.004). During the 5-minute period, spontaneous sBRS exhibited variations
      (CV=21.7+/-1.7%) that were negatively correlated with AP in five subjects (R=
      0.61+/-0.03, P<0.05) and positively correlated with MSNA in ten subjects
      (R=0.73+/-0.03, P<0.05). The new method is able to correctly estimate sBRS, and
      reveals the existence of previously unrecognized fast fluctuations of sBRS.

PMID- 22621852
TI  - Cultural differences in depression-related stigma in late-life: a comparison
      between the USA, Russia, and South Korea.
AB  - BACKGROUND: Depression is a common and treatable illness in late-life. However,
      many do not seek treatment and may suffer from the stigma of the illness, which
      may vary across cultures. The aim of this study was to compare attitudes about
      depression in primary care practices in South Korea, Russia, and the USA.
      METHODS: A cross-sectional study was undertaken using a self-administered
      questionnaire and PHQ-9 diagnostic survey with 1,094 patients aged 60-93 years
      who attended a primary care clinic in Korea, Russia, or the USA. RESULTS: The
      mean age of participants was 71 years, with 61% being female. US patients were
      older and had higher education levels. Russian participants were more likely to
      be widowed and had lower self-rated health. The majority of participants agreed
      that depression is a kind of disease (Korea 77%, Russia 61%, USA 79%). Only 6% of
      US patients believed depression means a person is weak, compared to 78% (Korea)
      and 61% (Russia). Fewer US patients endorsed depression as a normal part of aging
      (29% vs. Korea at 42% and Russia at 54%). Among participants in the USA, age
      correlated negatively with endorsement of a medical model of depression (p =
      <0.001). CONCLUSIONS: Though there was wide variation between countries in
      attitudes about depression, the majority of each endorsed items reflected a
      medical model of depression. Korean and Russian participants endorsed the view of
      depression as a personal weakness more than participants in the USA. Demographic
      correlates of negative attitudes about depression were moderate to weak.

PMID- 22621853
TI  - Role of host reticulon proteins in rearranging membranes for positive-strand RNA
      virus replication.
AB  - Positive-strand RNA [(+)RNA] viruses are responsible for numerous human, animal,
      and plant diseases. Because of the limiting coding capacity of (+)RNA viruses,
      their replication requires a complex orchestration of interactions between the
      viral genome, viral proteins and exploited host factors. To replicate their
      genomic RNAs, (+)RNA viruses induce membrane rearrangements that create membrane
      linked RNA replication compartments. Along with substantial advances on the
      ultrastructure of the membrane-bound RNA replication compartments, recent results
      have shed light into the role that host factors play in rearranging these
      membranes. This review focuses on recent insights that have driven a new
      understanding of the role that the membrane-shaping host reticulon homology
      domain proteins (RHPs) play in facilitating the replication of various (+)RNA
      viruses.

PMID- 22621854
TI  - [Post-trauma mandibular osteoma].
AB  - INTRODUCTION: Osteomas are benign bone tumors with a slow progressive growth.
      These lesions are predominantly located in craniofacial sinuses, but other
      locations including mandible have been described. Their etiopathogenesis remains
      controversial. We report a case of post-trauma mandibular osteoma. Gardner
      syndrome was ruled out. OBSERVATION: A 31-year-old female patient consulted for a
      peri-mandibular swelling present for the previous two years. On radiological
      examination, a bone sclerotic lesion was observed, located on the right lower
      mandibular edge. Patient history documented an initial trauma at the lesion site.
      Surgery was performed and anatomopathological examination confirmed the diagnosis
      of compact osteoma. There was no recurrence one year after surgery. DISCUSSION:
      The etiopathogenesis of osteomas is controversial and several hypotheses are
      suggested. It is regarded as a true benign tumoral process, or abnormality of
      development, or as a reaction to trauma or infection. The development of osteoma
      after trauma has been described in several cases, notably in mandibular locations
      exposed to shocks (angle and lower edge). Multiple osteomas must mandatorily lead
      to screening for a Gardner's syndrome, because of the associated risk of colon
      cancer.

PMID- 22621855
TI  - [An abdominal tumor].

PMID- 22621856
TI  - [Iron therapy: Indications, limitations and modality].
AB  - During the past 10 years, the knowledge of iron metabolism has been
      revolutionized by the discovery of the main regulatory hormone of body iron:
      hepcidin. Meanwhile, new formulations of intravenous iron have been developed and
      are already or readily available. In this article, we review the recent
      pathophysiological mechanisms underlying anemia of chronic disease or due to iron
      deficiency. We describe the various treatment modalities of iron deficiency
      anemia using oral or intravenous route and the emerging indications of treatment
      with iron. Finally, we discuss the situations in which iron supplementation may
      be harmful.

PMID- 22621857
TI  - Bilateral medial foot compartment syndrome after an aerobics class: a case
      report.
AB  - The authors present an unusual case of bilateral medial foot compartment syndrome
      in a healthy woman after a low-intensity aerobics exercise class. The majority of
      compartment syndrome cases have occurred after trauma, such as combat crush
      injuries and motor vehicle accidents. We wish to call attention to a rare
      situation in which compartment syndrome occurs in a healthy young adult after low
      intensity exercise and highlight the necessity of a high clinical suspicion and a
      low threshold for fasciotomies to prevent irreversible muscle damage as a result
      of extremely high pressures. There is a paucity of cases on the clinical
      management and follow-up of this rare occurrence of compartment syndrome.

PMID- 22621858
TI  - Complete fifth ray amputation with peroneal tendon transfer--a staged surgical
      protocol.
AB  - Nonhealing neuropathic ulcers overlying the fifth metatarsal are frequently
      associated with cavus foot structure and are often complicated by osteomyelitis.
      Partial fifth ray amputation for metatarsal phalangeal joint ulceration and
      osteomyelitis is a time-proven procedure. Recurrent wounds and persistent
      osteomyelitis at the amputation stump or fifth metatarsal base create significant
      challenges in a cavus foot with neuropathy. Long-term success with removal of the
      entire fifth ray is largely dependent on preventing infection of the cuboid and
      maintaining peroneal tendon function. The described technique demonstrates our
      surgical principles and technical pearls in performing a staged complete fifth
      ray amputation with initial antibiotic bead placement and delayed peroneal tendon
      transfer. The peroneus longus tendon transfer has the advantage of preserving the
      eversion force to counterbalance the posterior tibial tendon and allowing the
      first ray to elevate, thereby alleviating some of the sagittal plane deformity
      associated with a cavus foot structure. The surgical tips and pearls are
      accompanied by procedure indications and incision planning options. To our
      knowledge, this is the first report of a staged protocol involving complete fifth
      ray resection, initial antibiotic bead placement, and delayed peroneus longus
      tendon transfer.

PMID- 22621859
TI  - Retrograde nail for tibiotalocalcaneal arthrodesis as a limb salvage procedure
      for open distal tibia and talus fractures with severe bone loss.
AB  - The treatment of complex fractures of the distal tibia, ankle, and talus with
      soft tissue damage, bone loss, and nonreconstructable joints for which the
      optimal timing for reduction and fixation has been missed is challenging. In such
      cases primary arthrodesis might be a treatment option. We report a series of
      multi-injured patients with severe soft tissue damage and bone loss, who were
      treated with a retrograde tibiotalocalcaneal arthrodesis nail as a minimally
      invasive treatment option for limb salvage. After a median follow-up of 5.4
      years, all patients returned to their former profession. The ankle and bone
      fusion was complete, with moderate functional results and quality of life.
      Calcaneotibial arthrodesis using a retrograde nail is a good treatment option for
      nonreconstructable fractures of the ankle joint with severe bone loss and poor
      soft tissue quality in selected patients with multiple injuries, in particular,
      those involving both lower extremities, as a salvage procedure.

PMID- 22621860
TI  - Recovery of motor function after intensive navigated transcranial magnetic
      stimulation: a case report of unexpected therapeutic effects.

PMID- 22621861
TI  - Field trials of a novel toolkit for evaluating 'intangible' values-related
      dimensions of projects.
AB  - A novel toolkit has been developed, using an original approach to develop its
      components, for the purpose of evaluating 'soft' outcomes and processes that have
      previously been generally considered 'intangible': those which are specifically
      values based. This represents a step-wise, significant, change in provision for
      the assessment of values-based achievements that are of absolutely key importance
      to most civil society organisations (CSOs) and values-based businesses, and fills
      a known gap in evaluation practice. In this paper, we demonstrate the
      significance and rigour of the toolkit by presenting an evaluation of it in three
      diverse scenarios where different CSOs use it to co-evaluate locally relevant
      outcomes and processes to obtain results which are both meaningful to them and
      potentially comparable across organisations. A key strength of the toolkit is its
      original use of a prior generated, peer-elicited 'menu' of values-based
      indicators which provides a framework for user CSOs to localise. Principles of
      participatory, process-based and utilisation-focused evaluation are embedded in
      this toolkit and shown to be critical to its success, achieving high face
      validity and wide applicability. The emerging contribution of this next
      generation evaluation tool to other fields, such as environmental values,
      development and environmental sustainable development, shared values, business,
      education and organisational change is outlined.

PMID- 22621862
TI  - Role of 11C-choline PET/CT in the re-staging of prostate cancer patients with
      biochemical relapse and negative results at bone scintigraphy.
AB  - AIM: to evaluate the utility of (11)C-choline PET/CT in prostate cancer (PC)
      patients who have demonstrated a biochemical recurrence and a negative bone
      scintigraphy (BS). MATERIALS AND METHODS: 123 consecutive PC patients (mean age
      67.6 years; range 54-83) with a biochemical relapse (mean PSA value 3.3ng/mL;
      range 0.2-25.5) after radical prostatectomy (RP) were included in our
      retrospective study. Patients underwent a BS that resulted negative and a (11)C
      choline PET/CT within 4 months from BS (range: 1 day to 4 months; mean: 2.5
      months). Validation of results was established by: (1) a positive biopsy, (2) a
      positive subsequent BS, CT or MR and (3) a normalization of (11)C-choline uptake
      after systemic therapy or a progression of the disease. RESULTS: (11)C-choline
      PET/CT was positive in 42/123 patients (34.1%). (11)C-choline PET/CT detected
      lesions in: bone (10 patients), lymph-nodes (20 patients), bone and lymph nodes
      (7 patients), bone and lung (1 patient), lymph-nodes and lung (1 patient), local
      relapse (3 patients). Overall, (11)C-choline PET/CT showed a total of 30 unknown
      bone lesions in 18/123 (14.6%) patients. CONCLUSION: (11)C-choline PET/CT showed
      a better sensitivity than BS in patients with biochemical relapse after RP: (11)C
      choline PET/CT detected unknown bone lesions in 18/123 (14.6%) patients.

PMID- 22621863
TI  - Designing bovine T cell vaccines via reverse immunology.
AB  - T cell responses contribute to immunity against many intracellular infections.
      There is, for example, strong evidence that major histocompatibility complex
      (MHC) class I-restricted cytotoxic T lymphocytes (CTLs) play an essential role in
      mediating immunity to East Coast fever (ECF), a fatal lymphoproliferative disease
      of cattle prevalent in sub-Saharan Africa and caused by Theileria parva. To
      complement the more traditional approaches to CTL antigen identification and
      vaccine development that we have previously undertaken we propose a use of
      immunoinformatics to predict CTL peptide epitopes followed by experimental
      verification of T cell specificity to candidate epitopes using peptide-MHC (pMHC)
      tetramers. This system, adapted from human and rodent studies, is in the process
      of being developed for cattle. Briefly, we have used an artificial neural network
      called NetMHCpan, which has been trained mainly on existing human, mouse, and non
      human primate MHC-peptide binding data in an attempt to predict the peptide
      binding specificity of bovine MHC class I molecules. Our data indicate that this
      algorithm needs to be further optimized by incorporation of bovine MHC-peptide
      binding data. When retrained, NetMHCpan may be used to predict parasite peptide
      epitopes by scanning the predicted T. parva proteome and known parasite CTL
      antigens. A range of pMHC tetramers, made "on-demand", will then be used to assay
      cattle that are immune to ECF or in vaccine trials to determine if CTLs of the
      predicted epitope specificity are present or not. Thus, pMHC tetramers can be
      used in one step to identify candidate CTL antigens and to map CTL epitopes. Our
      current research focuses on 9 different BoLA class I molecules. By expanding this
      repertoire to include the most common bovine MHCs, these methods could be used as
      generic assays to predict and measure bovine T cell immune responses to any
      pathogen.

PMID- 22621864
TI  - Explanatory models of depression and treatment adherence to antidepressant
      medication: a qualitative interview study.
AB  - BACKGROUND: Adherence to antidepressant medication is a challenging clinical
      issue, which reduces treatment efficacy: 30-60% of all patients commencing
      treatment with antidepressants are estimated to stop taking the medication within
      the first 12 weeks. Patients' personal beliefs about depression and
      antidepressants are regarded as central influences on adherence. OBJECTIVES: The
      aim was to gain detailed insight into patients' personal accounts of depression
      and use of antidepressant medication and to relate these accounts to the
      patients' self-reported level of adherence. METHODS: In-depth, qualitative
      interviews of 16 depressed patients one, four, eight and twelve months after
      hospital discharge supplemented by diagnostic interviews and self-report
      measures. Kleinman's notion of "explanatory model" was used as the theoretical
      perspective on the patients' illness narratives. Interview transcripts were
      analysed thematically with "explanatory models" as the starting point. RESULTS:
      Patients had ambiguous experiences of depression and antidepressants. Patients
      explained their illness and the medical treatment in experience-near terms.
      Explanations of the reasons for depression were psychosocial and biology and
      medicine were not central. However, taking antidepressant medication was a
      meaningful part of being admitted to hospital, and the adoption of the rhetoric
      and practices of biomedicine strengthened patients' sense of control and hope for
      recovery. If medicine was ineffective, the explanatory models legitimised
      alternative strategies towards recovery, including non-adherence. CONCLUSIONS:
      The patients' reasons for adhering to antidepressants included a range of diverse
      psychosocial issues, and could be regarded as a central part of their common
      sense illness management.

PMID- 22621865
TI  - The versatile use of exhaled volatile organic compounds in human health and
      disease.
AB  - Exhaled breath contains thousands of volatile organic compounds (VOCs) of which
      the composition varies depending on health status. Various metabolic processes
      within the body produce volatile products that are released into the blood and
      will be passed on to the airway once the blood reaches the lungs. Moreover, the
      occurrence of chronic inflammation and/or oxidative stress can result in the
      excretion of volatile compounds that generate unique VOC patterns. Consequently,
      measuring the total amount of VOCs in exhaled air, a kind of metabolomics also
      referred to as breathomics, for clinical diagnosis and monitoring purposes gained
      increased interest over the last years. This paper describes the currently
      available methodologies regarding sampling, sample analysis and data processing
      as well as their advantages and potential drawbacks. Additionally, different
      application possibilities of VOC profiling are discussed. Until now, breathomics
      has merely been applied for diagnostic purposes. Exhaled air analysis can,
      however, also be applied as an analytical or monitoring tool. Within the analytic
      perspective, the use of VOCs as biomarkers of oxidative stress, inflammation or
      carcinogenesis is described. As monitoring tool, breathomics can be applied to
      elucidate the heterogeneity observed in chronic diseases, to study the
      pathogen(s) responsible for occurring infections and to monitor treatment
      efficacy.

PMID- 22621866
TI  - Differential effects of oxyntomodulin and GLP-1 on glucose metabolism.
AB  - Glucagon-like peptide-1 (GLP-1) and oxyntomodulin (OXM) are peptide hormones
      secreted postprandially from the gut that stimulate insulin secretion in a
      glucose-dependent manner. OXM activates both the GLP-1 receptor (GLP1R) and the
      glucagon receptor (GCGR). It has been suggested that OXM acutely modulates
      glucose metabolism solely through GLP1R agonism. Because OXM activates the GLP1R
      with lower affinity than GLP-1, we generated a peptide analog (Q->E, OXMQ3E) that
      does not exhibit glucagon receptor agonist activity but retains the same affinity
      as OXM for GLP1R. We compared the effects of OXM and OXMQ3E in a glucose
      tolerance test and, to better characterize the effect on glucose metabolism, we
      performed controlled infusions of OXM or OXMQ3E during a hyperglycemic clamp
      performed in wild-type, Glp1r(-/-), and Gcgr(-/-) mice. Our findings show that
      OXM, but not OXMQ3E, activates the GCGR in vivo. Second, OXM and OXMQ3E improve
      glucose tolerance following an acute glucose challenge and during a hyperglycemic
      clamp in mice. Finally, OXM infusion during a glucose clamp reduces the glucose
      infusion rate (GIR) despite a simultaneous increase in insulin levels in Glp1r(-/
      ) mice, whereas OXM and OXMQ3E increase GIR to a similar extent in Gcgr(-/-)
      mice. In conclusion, activation of the GCGR seems to partially attenuate the
      acute beneficial effects on glucose and contributes to the insulinotropic action
      of oxyntomodulin.

PMID- 22621868
TI  - Tributyrin attenuates obesity-associated inflammation and insulin resistance in
      high-fat-fed mice.
AB  - The aim of this study was to investigate whether treatment with tributyrin (Tb; a
      butyrate prodrug) results in protection against diet-induced obesity and
      associated insulin resistance. C57BL/6 male mice fed a standard chow or high-fat
      diet were treated with Tb (2 g/kg body wt, 10 wk) and evaluated for glucose
      homeostasis, plasma lipid profile, and inflammatory status. Tb protected mice
      against obesity and obesity-associated insulin resistance and dyslipidemia
      without food consumption being affected. Tb attenuated the production of TNFalpha
      and IL-1beta by peritoneal macrophages and their expression in adipose tissue.
      Furthermore, in the adipose tissue, Tb reduced the expression of MCP-1 and
      infiltration by leukocytes and restored the production of adiponectin. These
      effects were associated with a partial reversion of hepatic steatosis, reduction
      in liver and skeletal muscle content of phosphorylated JNK, and an improvement in
      muscle insulin-stimulated glucose uptake and Akt signaling. Although part of the
      beneficial effects of Tb are likely to be secondary to the reduction in body
      weight, we also found direct protective actions of butyrate reducing TNFalpha
      production after LPS injection and in vitro by LPS- or palmitic acid-stimulated
      macrophages and attenuating lipolysis in vitro and in vivo. The results, reported
      herein, suggest that Tb may be useful for the treatment and prevention of obesity
      related metabolic disorders.

PMID- 22621867
TI  - Acute hypoxia induces hypertriglyceridemia by decreasing plasma triglyceride
      clearance in mice.
AB  - Obstructive sleep apnea (OSA) induces intermittent hypoxia (IH) during sleep and
      is associated with elevated triglycerides (TG). We previously demonstrated that
      mice exposed to chronic IH develop elevated TG. We now hypothesize that a single
      exposure to acute hypoxia also increases TG due to the stimulation of free fatty
      acid (FFA) mobilization from white adipose tissue (WAT), resulting in increased
      hepatic TG synthesis and secretion. Male C57BL6/J mice were exposed to FiO(2) =
      0.21, 0.17, 0.14, 0.10, or 0.07 for 6 h followed by assessment of plasma and
      liver TG, glucose, FFA, ketones, glycerol, and catecholamines. Hypoxia dose
      dependently increased plasma TG, with levels peaking at FiO(2) = 0.07. Hepatic TG
      levels also increased with hypoxia, peaking at FiO(2) = 0.10. Plasma
      catecholamines also increased inversely with FiO(2). Plasma ketones, glycerol,
      and FFA levels were more variable, with different degrees of hypoxia inducing WAT
      lipolysis and ketosis. FiO(2) = 0.10 exposure stimulated WAT lipolysis but
      decreased the rate of hepatic TG secretion. This degree of hypoxia rapidly and
      reversibly delayed TG clearance while decreasing [(3)H]triolein-labeled
      Intralipid uptake in brown adipose tissue and WAT. Hypoxia decreased adipose
      tissue lipoprotein lipase (LPL) activity in brown adipose tissue and WAT. In
      addition, hypoxia decreased the transcription of LPL, peroxisome proliferator
      activated receptor-gamma, and fatty acid transporter CD36. We conclude that acute
      hypoxia increases plasma TG due to decreased tissue uptake, not increased hepatic
      TG secretion.

PMID- 22621869
TI  - Hormone secretion in transgenic rats and electrophysiological activity in their
      gonadotropin releasing-hormone neurons.
AB  - Expression of GFP in GnRH neurons has allowed for studies of individual GnRH
      neurons. We have demonstrated previously the preservation of physiological
      function in male GnRH-GFP mice. In the present study, we confirm using biocytin
      filled GFP-positive neurons in the hypothalamic slice preparation that GFP
      expressing somata, axons, and dendrites in hypothalamic slices from GnRH-GFP rats
      are GnRH1 peptide positive. Second, we used repetitive sampling to study hormone
      secretion from GnRH-GFP transgenic rats in the homozygous, heterozygous, and wild
      type state and between transgenic and Wistar males after ~4 yr of backcrossing.
      Parameters of hormone secretion were not different between the three genetic
      groups or between transgenic males and Wistar controls. Finally, we performed
      long-term recording in as many GFP-identified GnRH neurons as possible in
      hypothalamic slices to determine their patterns of discharge. In some cases, we
      obtained GnRH neuronal recordings from individual males in which blood samples
      had been collected the previous day. Activity in individual GnRH neurons was
      expressed as total quiescence, a continuous pattern of firing of either low or
      relatively high frequencies or an intermittent pattern of firing. In males with
      both intensive blood sampling (at 6-min intervals) and recordings from their GnRH
      neurons, we analyzed the activity of GnRH neurons with intermittent activity
      above 2 Hz using cluster analysis on both data sets. The average number of pulses
      was 3.9 +/- 0.6/h. The average number of episodes of firing was 4.0 +/- 0.6/h.
      Therefore, the GnRH pulse generator may be maintained in the sagittal
      hypothalamic slice preparation.

PMID- 22621870
TI  - Cardiovascular-associated tracheobronchial obstruction in children.
AB  - Tracheobronchial compression of cardiovascular origin is an uncommon and
      frequently unrecognised cause of respiratory distress in children. The
      compression may be due to encircling vessels or dilated neighbouring
      cardiovascular structures. Bronchoscopy and detailed radiography, especially
      computed tomography and magnetic resonance imaging, are among the most powerful
      diagnostic tools. Few previous reports have addressed the relationship between
      bronchoscopic findings and underlying cardiovascular anomalies. The objective of
      this study was to correlate bronchoscopic and radiographic findings in children
      with cardiovascular-associated airway obstruction. A total of 41 patients were
      recruited for the study. Patients with airway obstruction were stratified on the
      basis of the aetiology of the cardiovascular structures and haemodynamics into an
      anatomy-associated group and a haemodynamics-associated group. In the anatomy
      associated group, stenosis and malacia were found with comparable frequency on
      bronchoscopy, and the airway obstructions were mostly found in the trachea (71%
      of patients). In the haemodynamics-associated group, malacia was the most common
      bronchoscopic finding (85% of patients), and nearly all locations of airway
      involvement were in the airway below the carina (90% of patients). The tracheal
      compression was usually caused by aberrant systemic branching arteries in the
      anatomy-associated group. In the haemodynamics-associated group, the causal
      relationships varied. Tracheal compression was often caused by lesions of the
      main pulmonary artery and aorta, whereas obstruction of the right main bronchus
      was caused by lesions of the main pulmonary artery and right pulmonary artery.
      The causes of left main bronchus compression were more diverse. In summary, the
      bronchoscopic presentations and locations are quite different between these two
      groups.

PMID- 22621871
TI  - Comparison between homografts and Freestyle(r) bioprosthesis for right
      ventricular outflow tract replacement in Ross procedures.
AB  - OBJECTIVES: Although data from large series indicate the satisfactory performance
      of bioprosthetic valves in the right ventricular outflow tract (RVOT),
      replacement of the pulmonary valve in adult patients undergoing the Ross
      procedure is usually performed with pulmonary allografts. We evaluated the
      outcomes of homografts vs. bioprosthetic RVOT replacement after the Ross
      procedure in adults. METHODS: Between 1996 and 2011, a total of 186 adult
      patients (141 male; mean age 44 +/- 10 years) underwent aortic root replacement
      with a pulmonary autograft. The RVOT was replaced with a homograft in 113
      patients and with stentless bioprostheses (Medtronic Freestyle((r))) in 73.
      Patients were followed for a mean of 6 years (range 1-15 years; 1106 patient
      years). RESULTS: Twelve patients required reintervention owing to dysfunction of
      the RVOT replacement, which was caused by endocarditis (n = 4), degeneration (n =
      2) or stricture at the proximal suture line (n = 6). For homografts, the
      incidence of reintervention was 1 in 150 patient years, compared with 1 in 36
      patient years for stentless bioprostheses (P = 0.007). The median gradient was 15
      mmHg for the homograft group and 24 mmHg for bioprosthesis (P < 0.0001). The
      incidence of gradients >40 mmHg was 10-fold higher in the bioprosthetic group.
      CONCLUSIONS: Patients with bioprostheses in the RVOT position after the Ross
      procedure showed a significantly higher risk of reintervention or pulmonary valve
      dysfunction. The main problem, early development of a stricture at the proximal
      suture line, has to be solved to achieve satisfactory bioprosthetic function in
      the RVOT.

PMID- 22621872
TI  - First diagonal artery wrapping the left ventricular apex: an unusual course.

PMID- 22621873
TI  - Impact of preoperative atrial fibrillation on mortality and cardiovascular
      outcomes of mechanical mitral valve replacement for rheumatic mitral valve
      disease.
AB  - OBJECTIVES: The prognostic significance of preoperative atrial fibrillation on
      mitral valve replacement remains unclear. The aim of this study was to explore
      the effects of the presence of preoperative atrial fibrillation on mortality and
      cardiovascular outcomes of mitral valve replacement for rheumatic valve disease.
      METHODS: A retrospective analysis was performed on a total of 793 patients who
      underwent mitral valve replacement with or without tricuspid valve repair in our
      hospital. The patients selected were divided into two groups according to
      preoperative rhythm status. Patients with preoperative atrial fibrillation were
      assigned to the AF group, while patients in preoperative sinus rhythm were
      assigned to the SR group. Postoperative follow-up was performed by outpatient
      visits, as well as by telephone and written correspondence. Data gathered
      included survivorship, postoperative complications, left ventricular function and
      tricuspid regurgitation. RESULTS: For patients with atrial fibrillation vs those
      in sinus rhythm, there was no difference in postoperative mortality and
      morbidity. Follow-up was a mean of 8.6 +/- 2.4 years. For patients with
      preoperative atrial fibrillation, 10-year survival from a Kaplan-Meier curve was
      88.7%, compared with 96.6% in patients with preoperative sinus rhythm (P =
      0.002). Multivariate analysis identified low left ventricular ejection fraction,
      older age, large left atrium and preoperative atrial fibrillation as significant
      adverse predictors for overall survival. Freedom from thromboembolism
      complications at 13 years was lower for patients with preoperative atrial
      fibrillation without maze procedure and left atrial appendage ligation, compared
      with that for patients with preoperative sinus rhythm without maze procedure and
      left atrial appendage ligation, and patients with concomitant maze procedure and
      left atrial appendage ligation (76.3 vs 94.8 vs 94.0%, respectively; P = 0.001).
      On echocardiography, the proportion of patients with significant tricuspid
      regurgitation was 38.7% (atrial fibrillation patients) vs 25.4% (patients in
      sinus rhythm; P < 0.001). Left ventricular ejection fraction measured 5 years
      after surgery increased by an average of 1.2% in the AF group, while it increased
      by 5.3% in the SR group (P = 0.028). CONCLUSIONS: Preoperative atrial
      fibrillation is a risk factor for long-term mortality, thromboembolism
      complications and tricuspid regurgitation, and it also has an adverse effect on
      the degree of improvement when considering left ventricular function.

PMID- 22621874
TI  - Definitive therapy for isolated esophageal metastases prolongs survival.
AB  - BACKGROUND: Local and distant recurrences are frequent after curative resection
      for esophageal cancer and are considered uniformly fatal. However, some patients
      may present with isolated recurrences that appear amenable to definitive local
      therapy either by resection or chemoradiotherapy. We reviewed the clinical
      outcome of all patients with isolated nodal or distant metastases who were
      treated with curative intent. METHODS: In this retrospective review, all patients
      (n=561) who underwent curative resection for esophageal cancer from 1988 to 2011
      were identified from a prospectively assembled thoracic surgery database.
      Patients who had any type of recurrence were identified (n=205). In this group,
      27 patients were identified with isolated disease defined as single station of
      nodal disease or isolated distant metastases. Survival was modeled using the
      Kaplan-Meier method, and subgroup survival estimates were compared by the log
      rank test. The impact of age, sex, histology, pathology stage, site of
      recurrence, and treatment modality on mortality were analyzed by logistic
      regression. RESULTS: Twenty-seven patients (22 male, median age 61 years) had an
      isolated esophageal cancer recurrence; of those, 15 patients underwent surgical
      resection and 12 underwent definitive chemoradiation therapy. The sites of
      isolated recurrence were most commonly nodal. Median overall survival from time
      of recurrence was 25.2 months; 3-year estimated survival was 33.0% (confidence
      interval: 13.7 to 52.5). In univariate analysis, no relationship was formed.
      CONCLUSIONS: In appropriately selected patients with isolated esophageal
      metastases, definitive therapy can prolong survival. A long disease-free interval
      and recurrence limited to single nodal stations may select patients likely to
      have longer survival after definitive local therapy.

PMID- 22621875
TI  - Contemporary etiologies, risk factors, and outcomes after pericardiectomy.
AB  - BACKGROUND: The leading causes of constrictive pericarditis have changed over
      time leading to a commensurate change in the indications and complexity of
      surgical pericardiectomy. We evaluated our single-center experience to define the
      etiologies, risk factors, and outcomes of pericardiectomy in a modern cohort.
      METHODS: We retrospectively reviewed our institutional database for all patients
      who underwent total or partial pericardiectomy. Demographic, comorbid, operative,
      and outcome data were evaluated. Survival was assessed by the Kaplan-Meier
      method. Multivariable Cox proportional hazards regression models examined risk
      factors for mortality. RESULTS: From 1995 to 2010, 98 adults underwent
      pericardiectomy for constrictive disease. The most common etiologies were
      idiopathic (n=44), postoperative (n=30), and post radiation (n=17). Total
      pericardiectomy was performed in 94 cases, most commonly through a sternotomy
      (n=93). Thirty-three cases were redo sternotomies, 34 underwent a concomitant
      procedure, and 34 required cardiopulmonary bypass. Overall in-hospital, 1-year, 5
      year, and 10-year survival rates were 92.9%, 82.5%, 64.3%, and 49.2%,
      respectively. Survival differed sharply by etiology with idiopathic,
      postoperative, and post-radiation 5-year survivals of 79.8%, 55.9%, and 11.0%,
      respectively (p<0.001). On multivariable analysis, only the need for
      cardiopulmonary bypass (hazard ratio [HR]: 21.2, p=0.02) was predictive of 30-day
      mortality while post-radiation etiology (HR: 3.19, p=0.02) and hypoalbuminemia
      (HR: 0.57, p=0.03) were associated with increased 10-year mortality. CONCLUSIONS:
      Although survival varies significantly by etiology, pericardiectomy continues to
      be a safe operation for constrictive pericarditis. Post-radiation pericarditis
      and hypoalbuminemia are significant risk factors for decreased long-term
      survival.

PMID- 22621876
TI  - Pathologic lymph node ratio is a predictor of survival in esophageal cancer.
AB  - BACKGROUND: A ratio between pathologic and examined lymph nodes may have
      predictive relevance in esophageal cancer. We sought to determine the prognostic
      value of lymph node ratio (LNR) compared with TNM and N stage using the seventh
      edition American Joint Commission on Cancer and International Union Against
      Cancer criteria. METHODS: We abstracted data from 347 consecutive patients
      undergoing esophagectomy for esophageal cancer between 1999 and 2010 at our
      institution. Patients were stratified into surgery alone or induction therapy
      followed by surgery. Kaplan-Meier and Cox proportional hazard models estimated
      the survival function using LNR as a continuous variable or categorized into 0,
      more than 0.0 to less than 0.1, 0.1 to less than 0.2, 0.2 to less than 0.3, and
      0.3 or greater. The influence of LNR on survival was assessed by the Wald chi(2)
      statistic and survival plots. RESULTS: A total of 173 patients (49.9%) underwent
      induction therapy. The pathologic complete response rate was 55 of 173 (32%). The
      median number of examined nodes in surgery alone was 14 (interquartile range, 8
      to 21), and induction was 12 (interquartile range, 7 to 17). Patients with nodal
      disease (n = 137) had a median LNR of 0.2 with equivalent survival regardless of
      induction therapy. Examination of LNR as a continuous variable demonstrated that
      LNR is an independent predictor of survival in both groups. After categorization,
      LNR contributed more toward estimating survival than pN stage in both groups.
      CONCLUSIONS: Lymph node ratio is an independent predictor of survival in patients
      undergoing esophagectomy for esophageal cancer. The LNR makes a greater
      contribution in estimating overall survival than pN stage, regardless of the
      utilization of induction therapy.

PMID- 22621877
TI  - Late outcomes with repair of penetrating thoracic aortic ulcers: the merits of an
      endovascular approach.
AB  - BACKGROUND: Penetrating aortic ulcers (PAU) often occur in a debilitated elderly
      population. Although early results of repair for PAU are well described, late
      outcomes remain poorly characterized and are the focus in this report. METHODS:
      Ninety-five patients (mean age 70.7 years) underwent distal arch/descending
      aortic repair for PAU (1993 to 2011). Indications for intervention included
      rupture, saccular aneurysm, or symptoms. Associated intramural hematoma (IMH) was
      present in 41. Treatment was by open descending aortic repair (DTAR, n=37) or
      thoracic endovascular aortic repair (TEVAR, n=58). The DTAR group was younger (68
      years versus TEVAR 72.5 years, p=0.02), and less frequently presented with
      rupture (24% versus TEVAR 43%, p=0.09). RESULTS: Early morbidity included death
      (9 patients; 9.5%), stroke (8), permanent paraplegia (2), and dialysis (5). Early
      adverse events were independently predicted by rupture, total descending repair,
      and DTAR (all p<0.01). Ten-year survival was 47.9%. Predictors of late mortality
      included advancing age (p=0.016) and urgent presentation (p=0.002), but not
      repair type. Ten-year freedom from aortic reintervention/rupture was 71.4%.
      Associated IMH increased the risk for reintervention/rupture (5-year freedom PAU
      97.1% versus PAU/IMH 72.1%, p=0.01), primarily because of decreased efficacy
      after TEVAR for PAU/IMH (5-year freedom 57.7% versus DTAR 100%, p=0.05).
      CONCLUSIONS: Despite the presence of an older, more complex TEVAR group, late
      outcomes after repair for PAU were affected more by age and type of presentation
      than by treatment strategy. Recognizing the perils of intervention in this high
      risk population, TEVAR emerges as the therapy of choice to reduce early morbidity
      and provide similar late survival.

PMID- 22621878
TI  - Dengue virus infection in Australia following occupational exposure: a reflection
      of increasing numbers of imported cases.

PMID- 22621879
TI  - Occurrence, accumulation, attenuation and priority of typical antibiotics in
      sediments based on long-term field and modeling studies.
AB  - Long-term field and modeling studies were performed to measure and predict
      occurrence, accumulation, attenuation and priority of typical antibiotics in
      sediments of the Dagu River in China. The results indicated that the
      concentrations of antibiotics ranged from lower than the limit of detection to
      12.4mg/kg, depending on the accumulation time of these antibiotics in sediments.
      Compared with the residential and industrial areas, the agricultural region of
      the watershed was a major source of antibiotic contamination in sediments.
      Accumulation and attenuation kinetics models were established and successfully
      applied in the field study. For instance, by 2100, the accumulation model
      predicted that the concentrations of roxithromycin and oxytetracycline would rise
      to 13 and 7.3mg/kg, respectively. The first and second order attenuation kinetics
      models revealed the fate of these antibiotics along the downstream and upstream
      sediments, respectively. The half-life distances of antibiotic attenuation ranged
      from 3.5 to 12.4km. Based on the contamination level and trend, a priority factor
      and an accumulation growth factor were defined to identify the priority
      pollutants from the antibiotics. Gentamicin and roxithromycin were recognized as
      the top priority pollutants among the tested antibiotics. In the future, a wider
      applicability of the methods and models needs to be explored and suggested.

PMID- 22621880
TI  - In vivo screening to determine neurological hazards of nitrogen dioxide (NO2)
      using Wistar rats.
AB  - NO(2) is a well-known indoor and outdoor pollutant that may cause adverse health
      problems. Recently, accumulating but extremely limited evidences show that NO(2)
      possibly express neurotoxicity and is responsible for various neurological
      disorders. In the present study, neurological hazard of NO(2) and possible
      mechanisms were determined in rat pallium following a repetitive inhalation
      exposure with various concentrations (5, 10 and 20mg/m(3)). After 7-day exposure
      (6h/day), observable adverse effects were induced encompassing decreased ratio of
      brain to body weight, mild brain pathology, increased neuronal apoptosis, altered
      antioxidants (Cu/Zn-SOD, Mn-SOD, GPx and NO) activity and increasing formation of
      PCO. NO(2) inhalation also induced augment of oncogenes (c-fos, c-jun) levels,
      and deregulation of apoptosis-related genes (p53, bax and bcl-2) expression. With
      all above data, the present report provided essential information for the
      characterization of the neurotoxic hazard of NO(2) and related mechanisms, which
      is required in response to the general concern about the vulnerability of the
      neurological system to it.

PMID- 22621881
TI  - Human MCG measurements with a high-sensitivity potassium atomic magnetometer.
AB  - Measuring biomagnetic fields, such as magnetocardiograms (MCGs), is important for
      investigating biological functions. To address to this need, we developed an
      optically pumped atomic magnetometer. In this study, human MCGs were acquired
      using a potassium atomic magnetometer without any modulating systems. The
      sensitivity of the magnetometer is comparable to that of high-T(c)
      superconducting quantum interference devices (SQUIDs) and is sufficient for
      acquiring human MCGs. The activity of a human heart estimated from the MCG maps
      agrees well with that measured with SQUID magnetometers. Thus, our magnetometer
      produces reliable results, which demonstrate the potential of our atomic
      magnetometer for biomagnetic measurements.

PMID- 22621882
TI  - Quantification of tapentadol in canine plasma by HPLC with spectrofluorimetric
      detection: development and validation of a new methodology.
AB  - Tapentadol (TAP) is a novel opioid pain reliever drug that is unusual in its
      possession of dual mechanism of action (mu opioid-receptor agonist and
      noradrenaline reuptake inhibitor), this feature makes the active ingredient an
      attractive potential progenitor of a new pharmacological class. A liquid
      chromatography-mass spectrometry (LC-MS) method exists to measure TAP in urine
      and saliva, but the aim of the present study was to develop and validate a simple
      HPLC-FL based method to quantify TAP in plasma. Several parameters both in the
      extraction and detection method were evaluated. The applicability of the method
      was determined by administering TAP orally to two dogs; the protocol yielded the
      expected pharmacokinetic results and plasma collected by jugular venipuncture at
      regular intervals. The mobile phase consisted of acetonitrile (A):acetic acid (B)
      (33 mM), delivered in gradient mode (5-95% B [0-20 min], 95-5% B [20-25 min] and
      finally 5% B isocratically [25-32 min]) with a flow rate of 1 mL min-1.
      Excitation and emission wavelengths were of 273 and 298 nm, respectively. TAP was
      extracted from the plasma using a mixture of Et2O:CH2Cl2 (7:3, v/v), which gave a
      recovery of 98.0-107.8% and a limit of quantification of 1 ng mL-1. The
      chromatographic runs were specific with no interfering peaks at the retention
      times of the analyte and IS (O-desmethyltramadol), as confirmed by HPLC-DAD
      experiments. In conclusion, this was a simple and effective method using HPLC-FL
      to detect TAP in plasma, which may be useful for future pharmacokinetic studies.

PMID- 22621883
TI  - Use of ionic liquids as stationary phases in hyphenated gas chromatography
      techniques.
AB  - In the past decades a consistent number of ionic liquids have been specifically
      synthesized and evaluated as stationary phase in gas chromatography. Ionic
      liquid, also defined as "molten salts", are a class of organic non-molecular
      solvents liquid at room temperature (RTILs) that satisfy most of the requirements
      of a GC stationary phase, among which a high viscosity, the possibility to tune
      the selectivity (by changing the cation-anion combination) and a high thermal
      stability. The choice of the proper stationary phase plays a key role in the
      improvement/optimization of a GC method, and although the use of IL as stationary
      phases is still not well-established, the general interest in their applications
      has greatly increased, thanks to their particular properties. The present
      contribution provides an overview on recent evaluations and applications of IL
      stationary phases, focusing in particular on the use of these novel tools in
      hyphenated GC-based techniques.

PMID- 22621884
TI  - Comprehensive analysis of the toxic and refractory pollutants in acrylonitrile
      butadiene-styrene resin manufacturing wastewater by gas chromatography
      spectrometry with a mass or flame ionization detector.
AB  - Acrylonitrile-butadiene-styrene (ABS) resin manufacturing wastewater is a
      complicated, toxic and refractory industrial wastewater. Comprehensive and
      accurate analysis of the typical pollutants in ABS resin manufacturing wastewater
      is critical to develop cost-effective wastewater treatment technologies. In this
      paper, a comprehensively qualitative analysis combined with three complementary
      methods has been developed for the detection of typical pollutants in ABS resin
      manufacturing wastewater from three production sections, and thirty-seven
      compounds had been detected and further confirmed by this analysis method with
      standards. Simultaneous chromatographic separation and quantification of seven
      representative pollutants, including three mononuclear aromatics, three
      acrylonitrile dimers and one acrylonitrile derivative, were achieved by GC-FID
      system. The detection limits of this method for seven representative pollutants
      were in the range of 0.007-0.89 mg/L. The within-day and between-day precisions
      of this method were less than 6.5% (RSD, n=6). The recoveries of the
      representative pollutants reached 90-120%. The ABS resin manufacturing wastewater
      from E zone was successfully determined by this method, with two mononuclear
      aromatics and three acrylonitrile dimers accounting for 57.73% and 40.63% of the
      selected seven compounds, respectively. These results reveal that the removal of
      mononuclear aromatics and acrylonitrile dimers is a key to treat this wastewater.

PMID- 22621885
TI  - Understanding the molecular recognition between antibody fragments and protein A
      biomimetic ligand.
AB  - Affinity chromatography with protein A from Staphylococcus aureus (SpA) is the
      most widespread and accepted methodology for antibody capture during the
      downstream process of antibody manufacturing. A triazine based ligand (ligand
      22/8) was previously developed as an inexpensive and robust alternative to SpA
      chromatography (Li et al. and Teng et al.). Despite the experimental success,
      there is no structural information on the binding modes of ligand 22/8 to
      antibodies, namely to Immunoglobulin G (IgG) molecules and fragments. In this
      work, we addressed this issue by a molecular docking approach allied to molecular
      dynamics simulations. Theoretical results confirmed the preference of the
      synthetic ligand to bind IgG through the binding site found in the
      crystallographic structure of the natural complex between SpA and the Fc fragment
      of IgG. Our studies also suggested other unknown "hot-spots" for specific binding
      of the affinity ligand at the hinge between V(H) and C(H)1 domains of Fab
      fragment. The best docking poses were further analysed by molecular dynamics
      studies at three different protonation states (pH 3, 7 and 11). The main
      interactions between ligand 22/8 and the IgG fragments found at pH 7 were weaker
      at pH 3 and pH 11 and in these conditions the ligand start losing tight contact
      with the binding site, corroborating the experimental evidence for protein
      elution from the chromatographic adsorbents at these pH conditions.

PMID- 22621886
TI  - Aqueous two-phase affinity partitioning systems: current applications and trends.
AB  - Aqueous two-phase systems (ATPS) have been studied and used for product recovery
      and purification from diverse biological sources. ATPS are characterized by their
      versatility, easy scale up parameters, process integration capability and
      relative low cost. This technique is commonly regarded as a primary recovery
      stage mainly due to its low selectivity. However, the use of strategies involving
      the modification of ATPS with affinity ligands have resulted in significant
      increases in recovery yields and purification folds of biological products. The
      aim of this review is to highlight current applications, trends and challenges
      regarding affinity partitioning in aqueous two-phase systems for the
      fractionation, recovery and purification of biological products.

PMID- 22621887
TI  - Supercritical fluid extraction and chromatography.

PMID- 22621888
TI  - Restricted-access nanoparticles for magnetic solid-phase extraction of steroid
      hormones from environmental and biological samples.
AB  - Restricted-access materials based on non-ionic surfactant-coated dodecyl
      functionalized magnetic nanoparticles were prepared and applied to extract
      steroid hormones from environmental and biological samples. The magnetic
      nanoparticles were synthesized by co-precipitation, and were functionalized with
      dodecyltriethoxysilane, giving dodecyl-grafted magnetic nanoparticles (C12
      Fe3O4). They were further modified with different non-ionic surfactants by self
      assembly adsorption. Several types of non-ionic surfactants, Tween-20, 40, 60 and
      85, and Span-40, 60 and 80, were investigated as the coatings. Tween surfactants
      coated C12-Fe3O4, named as TW-20 (40, 60, 85)-C12, exhibited good dispersibility
      in aqueous solution, which was a preferred character in extraction; besides, TW
      20-C12 and TW-40-C12 showed good anti-interference ability and satisfactory
      reproducibility when they were used as magnetic solid-phase extraction (MSPE)
      sorbents. The factors that may influence the extraction, including the amount of
      magnetic nanoparticles, extraction and desorption time, the amount of salt
      addition, the type and volume of desorption solvent, the volume of methanol
      addition and pH of sample solution, were investigated in detail. High performance
      liquid chromatography-UV detection was employed for analysis of target analytes
      (steroid hormone compounds). The developed method was successfully used for the
      determination of the target analytes in environmental and urine samples. Both
      tested materials afforded good recovery, satisfactory reproducibility and low
      limits of detection for environmental samples, which indicates that the materials
      possessed anti-interference ability. However, compared to TW-40-C12, TW-20-C12
      nanoparticles provided better recovery in relatively complex biological samples,
      which may indicate that the latter one is more appreciated in complex samples.

PMID- 22621889
TI  - Effect of Henry's law constant and operating parameters on vacuum-assisted
      headspace solid phase microextraction.
AB  - Nonequilibrium headspace solid-phase microextraction (HSSPME) sampling under
      vacuum conditions may dramatically improve extraction kinetics compared to
      regular HSSPME at room temperature. This paper investigates the effects of
      organic analyte properties and sampling parameters (headspace volume and sample
      agitation) on vacuum-assisted HSSPME (Vac-HSSPME). It was found that at room
      temperature, acceleration effects on extraction rates induced by reducing the
      total pressure of the sample container are important for those compounds where
      the Henry's law constant, K(H), is close or below the reported threshold values
      for low K(H) solutes. For these compounds evaporation rate is controlled by mass
      transfer resistance in the thin gas-film adjacent to the gas/sample interface and
      reducing the total pressure will increase evaporation rates and result in a
      faster overall extraction process. Conversely, for analytes with an intermediate
      K(H) value, Vac-HSSPME is not expected to improve extraction rates compared to
      regular HSSPME given that mass transfer resistance in the liquid-film becomes
      important. In accordance with the theory, at equilibrium, the amount of analyte
      extracted by the SPME fiber is not affected by the pressure conditions inside the
      sample container. Furthermore, Vac-HSSPME extraction kinetics for low K(H)
      analytes were marginally affected by the tested change in headspace volume as
      evaporation rates dramatically increase under reduced pressure conditions and the
      sample responds much faster to the concentration drops in the headspace when
      compared to regular HSSPME. At equilibrium however, increasing the headspace
      volume may result in a loss of sensitivity for Vac-HSSPME similar to that
      observed for regular HSSPME. As expected, stirring the liquid sample was found to
      improve Vac-HSSPME. Finally, the method yielded a linearity of 0.998 and
      detection limits in the ppt level. The precision varied between 1.8% and 8.4%.

PMID- 22621890
TI  - Two-dimensional liquid chromatography of polystyrene-polyethylene oxide block
      copolymers.
AB  - In this study, liquid chromatography at critical conditions of polystyrene (PS)
      and polyethylene oxide (PEO) is used as the first dimension for the two
      dimensional analysis of PS-b-PEO copolymers. Comprehensive two-dimensional liquid
      chromatography, with size exclusion chromatography as the second dimension,
      reveals information about the molar mass distributions of all separated fractions
      from the first dimension. Furthermore, fractions eluting at the critical
      conditions of one block were collected and subjected to analysis in the second
      dimension at the critical conditions of the other block. These fractions were
      analysed by FTIR to determine their chemical compositions. The combination of the
      above approaches and the calibration of the evaporative light scattering (ELS)
      detector for the first-dimensional analysis yield deep insights into the
      molecular heterogeneity of the block copolymer samples. The composition of the
      samples and the chemical composition of the real block copolymer are also
      calculated by combining results obtained at both critical conditions.

PMID- 22621891
TI  - Metrics of separation performance in chromatography: Part 2. Separation
      performance of a heating ramp in temperature-programmed gas chromatography.
AB  - Metrics of separation performance described in Part 1 of this series were applied
      here to theoretical evaluation of performance of a heating ramp in temperature
      programmed GC. As in Part 1, the dependence of the separation (Deltas) of two
      arbitrarily spaced peaks (the number of sigma-slots between them) on operational
      parameters of GC analysis was treated here as the main building block for
      construction of other performance metrics. Simple expressions describing Deltas
      of two peaks eluting during isobaric linear heating ramp and dependence of Deltas
      on the heating rate, on column efficiency and on the peak spacing were derived.
      The use of dimensionless heating rate and other dimensionless operational
      parameters made these expressions universally suitable for different column
      dimensions, heating rates, carrier gas types, flow rates, etc. The use of
      dimensionless parameters also made it possible to express Deltas as a simple
      function of the earlier introduced chromatographically meaningful characteristic
      parameters of thermodynamics of solute-column interactions. The expressions for
      Deltas developed here, together with the ones described in Part 1 were used for
      theoretical prediction of total separation capacity (s(c)), total peak capacity
      (n(c)), and total number of resolved peaks in temperature-programmed analysis
      controlled by a balanced temperature program consisting of a linear heating ramp
      preceded by specially designed balanced temperature plateau. A numerical example
      of these parameters for a particular column, heating rate, carrier gas, and its
      flow rate is also provided. It has been shown that n(c) obtainable in temperature
      programmed analysis is 2-3 times larger than that obtainable in equally long
      isothermal analysis using the same column and gas. Comparison of this improvement
      with potentially more than an order of magnitude larger peak capacity of GC*GC
      has been discussed. Also described are the speed of analysis (the number of sigma
      slots per unit of time), and other characteristics of the separation performance
      of a heating ramp. In many respects, metric Deltas is similar to the widely known
      metric of resolution (R(s)). Advantages of Deltas over R(s) as a metric of the
      separation performance, as well as the advantages of other metrics utilized here
      over their widely known counterparts are discussed.

PMID- 22621892
TI  - Successful treatment of neonatal pulmonary thrombosis in congenital nephrotic
      syndrome.
AB  - A 21-year-old adult patient with Tetralogy of Fallot presented acutely unwell
      with a 3-month history of general malaise following dental treatment. Following
      initial complete repair, he subsequently underwent two right ventricular outflow
      tract reconstructions with conduits. On admission, transthoracic echocardiography
      and peripheral blood cultures were suggestive of streptococcal endocarditis.
      Sequential computed tomography pulmonary angiography demonstrated peripheral
      emboli with progressive central pulmonary artery filling defects suggestive of
      thrombi and potential vegetations (Fig 1a and b). Urgent surgery was performed
      for uncontrolled sepsis and increasing hypoxia. Peri-operative transesophageal
      echocardiogram confirmed previous findings (Fig 1c; Supplementary Video 1).
      Having resected the conduit, we performed a peripheral pulmonary embolectomy and
      resected an abundance of the infected material from the pulmonary arterial tree
      under low-flow hypothermia; we then proceeded with a jugular venous valved
      conduit (Contegra(r), Medtronic Inc, Minneapolis, Minnesota, United States of
      America) replacement and tricuspid valve annuloplasty. He made a slow but steady
      recovery and was discharged home in good health

PMID- 22621893
TI  - Neoadjuvant therapy and liver transplantation for hilar cholangiocarcinoma: is
      pretreatment pathological confirmation of diagnosis necessary?
AB  - BACKGROUND: Neoadjuvant chemoradiotherapy followed by operative staging and liver
      transplantation is an effective treatment for patients with unresectable hilar
      cholangiocarcinoma (CCA) and CCA arising in the setting of primary sclerosing
      cholangitis (PSC). Pathologic confirmation of CCA is notoriously difficult, and
      many patients have been treated based on clinical criteria without pathological
      confirmation. STUDY DESIGN: We reviewed our experience with the specific aim of
      determining the need for pathological confirmation of CCA before treatment.
      RESULTS: Two hundred and fifteen patients received neoadjuvant therapy between
      1992 and 2011. One hundred and eighty-two patients underwent operative staging
      and 38 (21%) had findings that precluded transplantation. Pathological
      confirmation of CCA before therapy was achieved in 45 of 87 (52%) PSC patients
      and 22 of 49 (45%) de novo patients who underwent transplantation. Pretreatment
      pathological confirmation was associated with significantly worse 5-year survival
      after start of therapy for PSC patients (50% vs 80%; p = 0.001), but not for de
      novo patients (39% vs 48%; p = 0.27). Pretreatment pathological confirmation was
      associated with worse 5-year survival after transplantation for PSC patients (66%
      vs 92%; p = 0.01), but not for de novo patients (63% vs 65%; p = 0.71). The
      difference in the PSC patients was not due to recurrent cancer. Absence of
      pretreatment pathological confirmation did not result in less detection of
      residual CCA in the explanted livers or in less recurrence after transplantation.
      CONCLUSIONS: Rates of residual CCA in liver explants and recurrences after
      transplantation are comparable for patients with and without pretreatment
      pathological confirmation of CCA and attest to the accuracy of clinical
      diagnostic criteria. Pretreatment pathological confirmation of CCA is desirable
      but should not be a requirement for treatment.

PMID- 22621894
TI  - Revisit on the evolutionary relationship between alternative splicing and gene
      duplication.
AB  - Gene duplications and alternative splicing (AS) isoforms are two widespread types
      of genetic variations that can facilitate diversification of protein function. A
      number of studies claimed that after gene duplication, two AS isoforms with
      differential functions can be 'fixed', respectively, in each of the duplicate
      copies. This simple 'functional-sharing' hypothesis was recently challenged by
      Roux and Robinson-Rechavi (2011). Instead, they proposed a more sophisticated
      hypothesis, invoking that less alternative splicing genes tend to be duplicated
      more frequently, and single-copy genes are younger than duplicate genes, or the
      'duplicability-age' hypothesis for short. In this letter, we show that all these
      genome-wide analyses of AS isoforms actually did not provide clear-cut evidence
      to nullify the basic idea of functional-sharing hypothesis. After updating our
      understanding of genome-wide alternative splicing, duplicability and CNV (copy
      number variation), we argue that the foundation of the duplicability-age
      hypothesis remains to be justified carefully. Finally, we suggest that a better
      approach to resolving this controversy is the correspondence analysis of indels
      (insertions and deletions) between duplicate genes to the genomic exon-intron
      structure, which can be used to experimentally test the effect of functional
      sharing hypothesis.

PMID- 22621895
TI  - An ex situ evaluation of TBA- and MTBE-baited bio-traps.
AB  - Aquifer microbial communities can be investigated using Bio-traps((r)) ("bio
      traps"), passive samplers containing Bio-Sep((r)) beads ("bio-beads") that are
      deployed in monitoring wells to be colonized by bacteria delivered via
      groundwater flow through the well. When bio-beads are "baited" with organic
      contaminants enriched in (13)C, stable isotope probing allows assessment of the
      composition and activity of the microbial community. This study used an ex situ
      system fed by groundwater continuously extracted from an adjacent monitoring well
      within an experimentally-created aerobic zone treating a tert-butyl alcohol (TBA)
      plume. The goal was to evaluate aspects of bio-trap performance that cannot be
      studied quantitatively in situ. The measured groundwater flow through a bio-trap
      housing suggests that such traps might typically "sample" about 1.8 L per month.
      The desorption of TBA or methyl tert-butyl ether (MTBE) bait from bio-traps
      during a typical deployment duration of 6 weeks was approximately 90% and 45%,
      respectively, of the total initial bait load, with initially high rate of mass
      loss that decreased markedly after a few days. The concentration of TBA in
      groundwater flowing by the TBA-baited bio-beads was estimated to be as high as
      3400 mg/L during the first few days, which would be expected to inhibit growth of
      TBA-degrading microbes. Initial inhibition was also implied for the MTBE-baited
      bio-trap, but at lower concentrations and for a shorter time. After a few days,
      concentrations in groundwater flowing through the bio-traps dropped below
      inhibitory concentrations but remained 4-5 orders of magnitude higher than TBA or
      MTBE concentrations within the aquifer at the experimental site. Desorption from
      the bio-beads during ex situ deployment occurred at first as predicted by prior
      sorption analyses of bio-beads but with apparent hysteresis thereafter, possibly
      due to mass transfer limitations caused by colonizing microbes. These results
      suggest that TBA- or MTBE-baited bio-traps could be baited at lower initial total
      mass loading with no detriment to trapping ability. The bio-traps were able to
      collect detectable amounts of microbial DNA and thus allow some insight into the
      sparse microbial community present in the aquifer during remediation of the low
      concentration plume.

PMID- 22621896
TI  - The transcription factor Flo8 mediates CO2 sensing in the human fungal pathogen
      Candida albicans.
AB  - Physiological levels of CO(2) have a profound impact on prominent biological
      attributes of the major fungal pathogen of humans, Candida albicans. Elevated
      CO(2) induces filamentous growth and promotes white-to-opaque switching. However,
      the underlying molecular mechanisms of CO(2) sensing in C. albicans are
      insufficiently understood. Here we identify the transcription factor Flo8 as a
      key regulator of CO(2)-induced morphogenesis in C. albicans by screening a gene
      null mutant library. We show that Flo8 is required for CO(2)-induced white-to
      opaque switching, as well as for filamentous growth. Ectopic expression of FLO8
      hypersensitizes C. albicans cells to the elevated CO(2) levels. Furthermore, we
      demonstrate that CO(2) signaling in C. albicans involves two pathways: the
      already reported cAMP/protein kinase A and another major one that is
      unidentified. The two pathways converge on the transcription factor Flo8, which
      is the master regulator of CO(2) sensing in C. albicans and plays a critical role
      in regulation of white-to-opaque switching and filamentous growth. Our findings
      provide new insights into the understanding of CO(2) sensing in pathogenic fungi
      that have important implications for higher organisms.

PMID- 22621897
TI  - H4K16 acetylation affects recombination and ncRNA transcription at rDNA in
      Saccharomyces cerevisiae.
AB  - Transcription-associated recombination is an important process involved in
      several aspects of cell physiology. In the ribosomal DNA (rDNA) of Saccharomyces
      cerevisiae, RNA polymerase II transcription-dependent recombination has been
      demonstrated among the repeated units. In this study, we investigate the
      mechanisms controlling this process at the chromatin level. On the basis of a
      small biased screening, we found that mutants of histone deacetylases and
      chromatin architectural proteins alter both the amount of Pol II-dependent
      noncoding transcripts and recombination products at rDNA in a coordinated manner.
      Of interest, chromatin immunoprecipitation analyses in these mutants revealed a
      corresponding variation of the histone H4 acetylation along the rDNA repeat,
      particularly at Lys-16. Here we provide evidence that a single, rapid, and
      reversible posttranslational modification-the acetylation of the H4K16 residue-is
      involved in the coordination of transcription and recombination at rDNA.

PMID- 22621898
TI  - Plk1 negatively regulates PRC1 to prevent premature midzone formation before
      cytokinesis.
AB  - To achieve mitosis and cytokinesis, microtubules must assemble into distinct
      structures at different stages of cell division-mitotic spindles to segregate the
      chromosomes before anaphase and midzones to keep sister genomes apart and guide
      the cleavage furrow after anaphase. This temporal regulation is believed to
      involve Cdk1 kinase, which is inactivated in a switch-like way after anaphase. We
      found that inhibiting Plk1 caused premature assembly of midzones in cells still
      in metaphase, breaking the temporal regulation of microtubules. The antiparallel
      microtubule-bundling protein PRC1 plays a key role in organizing the midzone
      complex. We found that Plk1 negatively regulates PRC1 through phosphorylation of
      a single site, Thr-602, near the C-terminus of PRC1. We also found that
      microtubules stimulated Thr-602 phosphorylation by Plk1. This creates a potential
      negative feedback loop controlling PRC1 activity. It also made the extent of Thr
      602 phosphorylation during mitotic arrest dependent on the mechanism of the
      arresting drug. Unexpectedly, we could not detect a preanaphase regulatory role
      for Cdk1 sites on PRC1. We suggest that PRC1 is regulated by Plk1, rather than
      Cdk1 as previously proposed, because its activity must be spatiotemporally
      regulated both preanaphase and postanaphase, and Cdk1 activity is too binary for
      this purpose.

PMID- 22621899
TI  - Calmodulin activation of Aurora-A kinase (AURKA) is required during ciliary
      disassembly and in mitosis.
AB  - The centrosomal Aurora-A kinase (AURKA) regulates mitotic progression, and
      overexpression and hyperactivation of AURKA commonly promotes genomic instability
      in many tumors. Although most studies of AURKA focus on its role in mitosis, some
      recent work identified unexpected nonmitotic activities of AURKA. Among these, a
      role for basal body-localized AURKA in regulating ciliary disassembly in
      interphase cells has highlighted a role in regulating cellular responsiveness to
      growth factors and mechanical cues. The mechanism of AURKA activation involves
      interactions with multiple partner proteins and is not well understood,
      particularly in interphase cells. We show here that AURKA activation at the basal
      body in ciliary disassembly requires interactions with Ca(2+) and calmodulin
      (CaM) and that Ca(2+)/CaM are important mediators of the ciliary disassembly
      process. We also show that Ca(2+)/CaM binding is required for AURKA activation in
      mitosis and that inhibition of CaM activity reduces interaction between AURKA and
      its activator, NEDD9. Finally, mutated derivatives of AURKA impaired for CaM
      binding and/or CaM-dependent activation cause defects in mitotic progression,
      cytokinesis, and ciliary resorption. These results define Ca(2+)/CaM as important
      regulators of AURKA activation in mitotic and nonmitotic signaling.

PMID- 22621900
TI  - GGA1-mediated endocytic traffic of LR11/SorLA alters APP intracellular
      distribution and amyloid-beta production.
AB  - Proteolytic processing of the amyloid-beta precursor protein (APP) and generation
      of amyloid-beta peptide (Abeta) are key events in Alzheimer's disease (AD)
      pathogenesis. Cell biological and genetic evidence has implicated the low-density
      lipoprotein and sorting receptor LR11/SorLA in AD through mechanisms related to
      APP and Abeta production. Defining the cellular pathway(s) by which LR11
      modulates Abeta production is critical to understanding how changes in LR11
      expression affect the development of Abeta pathology in AD progression. We report
      that the LR11 ectodomain is required for LR11-mediated reduction of Abeta and
      that mutagenesis of the LR11 Golgi-localizing, gamma-adaptin ear homology domain,
      ADP-ribosylation factor (GGA)-binding motif affects the endosomal distribution of
      LR11, as well as LR11's effects on APP traffic and Abeta production. Targeted
      small interfering RNA (siRNA) knockdown studies of GGA1, GGA2, and GGA3 indicate
      a surprising degree of specificity toward GGA1, suggesting that GGA1 is a
      candidate regulator of LR11 traffic. Additional siRNA knockdown experiments
      reveal that GGA1 is necessary for both LR11 and beta-site APP-cleaving enzyme-1
      (BACE1) modulation of APP processing to Abeta. Mutagenesis of BACE1 serine 498 to
      alanine enhances BACE1 targeting to LR11-positive compartments and nullifies LR11
      mediated reduction of Abeta. On basis of these results, we propose that GGA1
      facilitates LR11 endocytic traffic and that LR11 modulates Abeta levels by
      promoting APP traffic to the endocytic recycling compartment.

PMID- 22621901
TI  - UNC-89 (obscurin) binds to MEL-26, a BTB-domain protein, and affects the function
      of MEI-1 (katanin) in striated muscle of Caenorhabditis elegans.
AB  - The ubiquitin proteasome system is involved in degradation of old or damaged
      sarcomeric proteins. Most E3 ubiquitin ligases are associated with cullins, which
      function as scaffolds for assembly of the protein degradation machinery. Cullin 3
      uses an adaptor to link to substrates; in Caenorhabditis elegans, one of these
      adaptors is the BTB-domain protein MEL-26 (maternal effect lethal). Here we show
      that MEL-26 interacts with the giant sarcomeric protein UNC-89 (obscurin). MEL-26
      and UNC-89 partially colocalize at sarcomeric M-lines. Loss of function or gain
      of function of mel-26 results in disorganization of myosin thick filaments
      similar to that found in unc-89 mutants. It had been reported that in early C.
      elegans embryos, a target of the CUL-3/MEL-26 ubiquitylation complex is the
      microtubule-severing enzyme katanin (MEI-1). Loss of function or gain of function
      of mei-1 also results in disorganization of thick filaments similar to unc-89
      mutants. Genetic data indicate that at least some of the mel-26 loss-of-function
      phenotype in muscle can be attributed to increased microtubule-severing activity
      of MEI-1. The level of MEI-1 protein is reduced in an unc-89 mutant, suggesting
      that the normal role of UNC-89 is to inhibit the CUL-3/MEL-26 complex toward MEI
      1.

PMID- 22621902
TI  - Chromatin remodeling by the SWI/SNF complex is essential for transcription
      mediated by the yeast cell wall integrity MAPK pathway.
AB  - In Saccharomyces cerevisiae, the transcriptional program triggered by cell wall
      stress is coordinated by Slt2/Mpk1, the mitogen-activated protein kinase (MAPK)
      of the cell wall integrity (CWI) pathway, and is mostly mediated by the
      transcription factor Rlm1. Here we show that the SWI/SNF chromatin-remodeling
      complex plays a critical role in orchestrating the transcriptional response
      regulated by Rlm1. swi/snf mutants show drastically reduced expression of cell
      wall stress-responsive genes and hypersensitivity to cell wall-interfering
      compounds. On stress, binding of RNA Pol II to the promoters of these genes
      depends on Rlm1, Slt2, and SWI/SNF. Rlm1 physically interacts with SWI/SNF to
      direct its association to target promoters. Finally, we observe nucleosome
      displacement at the CWI-responsive gene MLP1/KDX1, which relies on the SWI/SNF
      complex. Taken together, our results identify the SWI/SNF complex as a key
      element of the CWI MAPK pathway that mediates the chromatin remodeling necessary
      for adequate transcriptional response to cell wall stress.

PMID- 22621904
TI  - Mice expressing aberrant sperm-specific protein PMIS2 produce normal-looking but
      fertilization-incompetent spermatozoa.
AB  - Eight kinds of gene-disrupted mice (Clgn, Calr3, Pdilt, Tpst2, Ace, Adam1a,
      Adam2, and Adam3) show impaired sperm transition into the oviducts and defective
      sperm binding to the zona pellucida. All of these knockout strains are reported
      to lack or show aberrant expression of a disintegrin and metallopeptidase domain
      3 (ADAM3) on the sperm membrane. We performed proteomic analyses of the proteins
      of these infertile spermatozoa to clarify whether the abnormal function is caused
      exclusively by a deficiency in ADAM3 expression. Two proteins, named PMIS1 and
      PMIS2, were missing in spermatozoa from Clgn-disrupted mice. To study their
      roles, we generated two gene-disrupted mouse lines. Pmis1-knockout mice were
      fertile, but Pmis2-knockout males were sterile because of a failure of sperm
      transport into the oviducts. Pmis2-deficient spermatozoa also failed to bind to
      the zona pellucida. However, they showed normal fertilizing ability when eggs
      surrounded with cumulus cells were used for in vitro fertilization. Further
      analysis revealed that these spermatozoa lacked the ADAM3 protein, but the amount
      of PMIS2 was also severely reduced in Adam3-deficient spermatozoa. These results
      suggest that PMIS2 might function both as the ultimate factor regulating sperm
      transport into the oviducts and in modulating sperm-zona binding.

PMID- 22621903
TI  - Calcium-calmodulin kinase I cooperatively regulates nucleocytoplasmic shuttling
      of CCTalpha by accessing a nuclear export signal.
AB  - We identified a new calmodulin kinase I (CaMKI) substrate, cytidyltransferase
      (CCTalpha), a crucial enzyme required for maintenance of cell membranes. CCTalpha
      becomes activated with translocation from the cytoplasm to the nuclear membrane,
      resulting in increased membrane phospholipids. Calcium-activated CCTalpha nuclear
      import is mediated by binding of its C-terminus to 14-3-3 zeta, a regulator of
      nuclear trafficking. Here CaMK1 phosphorylates residues within this C-terminus
      that signals association of CCTalpha with 14-3-3 zeta to initiate calcium-induced
      nuclear entry. CaMKI docks within the CCTalpha membrane-binding domain (residues
      290-299), a sequence that displays similarities to a canonical nuclear export
      signal (NES) that also binds CRM1/exportin 1. Expression of a CFP-CCTalpha mutant
      lacking residues 290-299 in cells results in cytosolically retained enzyme.
      CRM1/exportin 1 was required for CCTalpha nuclear export, and its overexpression
      in cells was partially sufficient to trigger CCTalpha nuclear export despite
      calcium stimulation. An isolated CFP-290-299 peptide remained in the nucleus in
      the presence of leptomycin B but was able to target to the cytoplasm with
      farnesol. Thus CaMKI vies with CRM1/exportin 1 for access to a NES, and assembly
      of a CaMKI-14-3-3 zeta-CCTalpha complex is a key effector mechanism that drives
      nuclear CCTalpha translocation.

PMID- 22621906
TI  - An orthotopic and osteolytic model with a newly established oral squamous cell
      carcinoma cell line.
AB  - OBJECTIVE: Despite the availability of advanced clinical diagnostic systems, the
      overall 5-year survival rate for patients with oral squamous cell carcinoma
      (OSCC) has remained relatively poor over the past 2 decades. Appropriate animal
      models need to be developed according to the specific purpose of cancer research.
      However, most of the currently available oral cancer cell lines do not precisely
      reflect the characteristics of bone-invasive OSCC and cannot serve as suitable
      tools in the development of new therapeutic reagents against bone-invasive OSCC.
      Here, we assessed the orthotopic and osteolytic mouse model with newly
      established OSCC cell line. DESIGN: We assessed the orthotopic and osteolytic
      mouse model using the newly established OSCC cells. In addition, the incidences
      of tumorigenesis and histopathological results were determined. RESULTS: The
      newly established YD-39 cell line grows in a monolayer sheet and has highly
      invasive. The transplanted YD-39 cells developed stable tumours in the tongues
      and calvaria region of the nude mice. The tumours in nude mice grafted with YD-39
      cells had a high incidence of transplantability in both mouse models tested and a
      similar morphology to their respective original tumour. Therefore, both animal
      models might be feasible animal models to assess the efficacy of anti-cancer
      drugs. CONCLUSIONS: This type of animal model approach might be has the added
      advantage of potentially accelerating the biological discovery process.

PMID- 22621905
TI  - Effect of pH on Galla chinensis extract's stability and anti-caries properties in
      vitro.
AB  - OBJECTIVES: Considering that Galla chinensis extract (GCE) solution has a low pH,
      which might dissolve dental enamel, we investigated the effects of elevation of
      pH on GCE stability, and on its anti-caries properties. DESIGNS: Stability of GCE
      solutions, either in H(2)O (pH less than 4.0) or when buffered at pH 5.5, 7.0 and
      10.0, was assessed from UV-VIS spectra. Inhibition of enamel demineralization was
      determined in a pH-cycling set up, comprising treatments with either GCE
      solutions or negative control buffers and acid and neutral buffer immersions.
      Demineralization was assessed by calcium in the acetate buffers. To determine
      antimicrobial properties, polymicrobial biofilms were formed after saliva
      inoculation on glass surfaces which were treated after 48 h. Treatment output
      parameters were lactic acid formation and viability, the latter by colony forming
      unit (CFU) counts. RESULTS: At pH 7.0 and higher GCE solutions changed colour and
      absorption spectra in UV-VIS, indicative of chemical changes. Regarding enamel
      demineralization, significant inhibitions (P<0.05) were found for all GCE
      treatments when compared with corresponding controls. In polymicrobial biofilms,
      GCE reduced the acid production, compared with the negative controls (P<0.05).
      However, this difference was only significant at the lower pH values.
      CONCLUSIONS: GCE solutions were unstable under neutral and alkaline conditions.
      pH did not significantly influence the inhibiting effect of GCE on enamel
      demineralization. However, GCE was not effective on polymicrobial biofilms at
      alkaline pH (8.5). To avoid enamel damage due to acidic treatment, GCE solutions
      should be used at about pH 5.5.

PMID- 22621907
TI  - Short communications published online in the British Journal of Oral and
      Maxillofacial Surgery during 2010-2011.
AB  - The British Journal of Oral and Maxillofacial Surgery (BJOMS) publishes many
      types of papers including original articles, review articles, and short
      communications. Many of the latter are isolated case reports of rare or
      interesting diseases or of difficult or unexpected complications. While case
      reports are sometimes considered to be of little educational or clinical value,
      and as such do little to advance medical knowledge, they do have an important
      role, and many trainees begin their publishing careers writing such papers. There
      is increasing pressure for space in paper medical journals and, for this reason,
      some journals either limit or do not publish short publications in print copy but
      instead put them online. Using established criteria, we previously evaluated all
      142 short communications published in the BJOMS during 2008-2009 and found that
      48% of them had little or no educational value. As a result, the editorial board
      of BJOMS took the decision to publish most short communications online only. We
      have now analysed 48 short communications that were published online only during
      2010-2011. Most (80%) were single case reports that covered virtually the whole
      remit of the specialty, and over half (56%) were published by authors based in
      the UK. While many of these papers did not add important new information to
      existing knowledge, these types of article are clearly of value both for trainees
      and for experienced surgeons. We think that these should continue to be supported
      as, in addition to their educational value, they are an excellent way for
      trainees to start to write.

PMID- 22621908
TI  - Latency to first interictal epileptiform discharge in epilepsy with outpatient
      ambulatory EEG.
AB  - OBJECTIVE: The diagnosis and classification of epilepsy often relies upon the
      demonstration of interictal epileptiform discharges (IEDs). Routine 20-min EEG
      recording has low sensitivity, with multiple EEGs increasing sensitivity to a
      maximum of 77% (Doppelbauer et al., 1993). An alternate strategy is the use of
      prolonged continuous EEG; however, there are no data on the average latency to
      first IED with ambulatory monitoring. METHODS: In this retrospective study we
      reviewed 180 consecutive patients with epilepsy referred to a Specialist Epilepsy
      Unit who had undergone 96 h outpatient ambulatory EEGs, without medication
      withdrawal, where IEDs were recorded. Latency to, and factors affecting first IED
      were analysed. RESULTS: Median latency to first IED was 316 min, (interquartile
      range 70-772 min, n=180). IEDs were recorded in 44% of patients within 4h, 58%
      within 8h, 85% within 24h and 95% within 48 h. Recording for the full 96 h period
      revealed only 5% further IEDs. Multivariate analysis showed the latencies to IEDs
      with generalised epilepsies were shorter than with focal epilepsies (p<0.0001).
      CONCLUSIONS: In 95% of patients showing scalp IEDs a 48 h recording was
      sufficient for electro-clinical classification in this study. SIGNIFICANCE: Our
      data are the first to show the latency to recording interictal epileptiform
      discharges with prolonged outpatient EEG monitoring. These data are important in
      guiding diagnostic practice in Specialist Epilepsy Services.

PMID- 22621909
TI  - Representation of cricothyroid muscles at the primary motor cortex (M1) in
      healthy subjects, mapped by navigated transcranial magnetic stimulation (nTMS).
AB  - OBJECTIVES: To establish a methodology for mapping of primary motor cortex (M1)
      for cricothyroid (CTHY) muscles in a group of healthy subjects using three
      dimensional (3D) magnetic resonance imaging (MRI) navigated transcranial magnetic
      stimulation (nTMS). METHODS: Two independent measurements were performed. Twelve
      right-handed healthy subjects were included in the study. In the first
      measurement, mapping of the abductor pollicis brevis (APB) muscle was followed by
      mapping of the M1 for CTHY. This was performed in 11 subjects. Second, to avoid
      bias concerning using a hand knob as a landmark, mapping of M1 for CTHY muscle
      was followed by mapping of M1 for APB. This was performed in three healthy
      subjects. The nTMS was used, with selective recordings of motor evoked potentials
      (MEPs) from APB muscle and corticobulbar motor evoked potentials (CoMEPs) from
      the CTHY muscle. For recording the responses from the CTHY muscle two hook wire
      electrodes (the size of 76 MUm of diametre passing through 27 gauge needle) were
      inserted in the muscle. For the recording of MEPs from APB muscle, surface
      electrodes were used. RESULTS: First measurement: Stimulation over the left M1
      for APB muscles elicits MEPs in the contralateral APB muscle with a mean latency
      of 22.8+/-1.69ms. Stimulation over the left M1 for the CTHY muscle elicits CoMEPs
      in the contralateral CTHY muscle with a mean latency of 11.89+/-1.26ms. The
      distance between the cortical representation for APB and CTHY was 25.19+/-6.52mm,
      with CTHY muscle representation lateral to the APB muscle. Second measurement:
      The results of second measurement of the distance between M1 for CTHY and M1 for
      APB and their cortical localisation were comparable to the results of the first
      measurement. CONCLUSION: This is the first study with the aim to determine the
      exact cortical localisation of CTHY muscle with nTMS. Mapping of M1 for CTHY and
      APB muscles by nTMS was successfully performed in all healthy subjects. The exact
      location of the stimulating points over M1 muscles eliciting responses in CTHY
      and APB muscles was determined and superimposed over 3D MRI images. The data show
      that M1 for CTHY muscle is about 25mm more lateral with regard to M1 for the APB
      muscle. SIGNIFICANCE: Mapping of M1 for CTHY muscle might represent an important
      neurophysiologic marker for facilitating preoperative mapping of motor speech
      related cortical areas due to the proximity of motor cortical representation for
      laryngeal muscles and opercular part of the Broca area.

PMID- 22621910
TI  - Association of fixed partial denture and gingival prosthesis as alternative
      approach to recover esthetics and function in anterior maxillary region.
AB  - Tooth replacement in the maxillary anterior region is especially difficult when
      the loss includes significant amounts of the residual ridge and the soft tissue.
      Several techniques are available, such as dental implants or fixed partial
      denture, and bone and gingival grafts or gingival prostheses, respectively. This
      article showed a clinical case of an elderly who was treated with a collarless
      metal-ceramic fixed partial denture and acrylic removable gingival prosthesis to
      recover the esthetics in the maxillary anterior region. The association of a
      metal-ceramic fixed denture and gingival prosthesis was an excellent alternative
      in cases when surgical procedures are contraindicated.

PMID- 22621912
TI  - Interaction between crystal violet and anionic surfactants at silica/water
      interface using evanescent wave-cavity ring-down absorption spectroscopy.
AB  - Evanescent wave-cavity ring-down spectroscopy (EW-CRDS) is employed to
      characterize micellization of anionic surfactants and the related capability of
      removing cationic substance off the silica surface. Crystal violet (CV(+))
      cationic dye is used as a molecular probe to effectively determine critical
      hemimicelle concentration (HMC) of surfactants on the surface. The HMC results
      are 1*10(-2), 4*10(-3), 8*10(-4), and 2.5*10(-4) mol/L for sodium sulfate salts
      with a carbon-chain length of C-10, C-12, C-14, and C-16, respectively. A
      stronger hydrophobic interaction results in a less concentration required to
      undergo micellization. The HMC values on the surface are about half of those in
      solution. When NaCl solution is added, the electrolyte helps reduce the
      electrostatic repulsion between the anionic sulfate heads to facilitate the
      surfactant aggregation, and thus, the subsequent HMC is reduced. Furthermore, the
      probable phase change for dye-surfactant interactions on the surface at the
      concentration below HMC is observed, and the desorption rates of CV(+) are
      measured as a function of concentration and carbon-chain length of surfactants
      above HMC. Given each surfactant concentration at its respective HMC, the
      corresponding desorption rates are along the order of C-12<C-14<C-16<-C-10. The
      trend may be realized by two competing factors of hemimicelle size and number
      density. The consequences help with understanding how to apply surfactant in the
      chromatographic separation.

PMID- 22621911
TI  - Effect of chemical modification on carbon dioxide adsorption property of
      mesoporous silica.
AB  - Three adsorbents were prepared by different modification methods, which were
      grafting silica gel with (3-aminopropyl) trimethoxysilane, grafting silica gel
      with acrylamide polymer, and impregnating silica gel with acrylamide polymer,
      respectively. The characterization of materials was carried out by N(2)
      adsorption experiments, Fourier transform infrared spectroscopy, scanning
      electron microscopy, thermo-gravimetric analysis, and elemental analyses. The
      results showed that the amine group was successfully loaded on all three modified
      adsorbents; among that, the polymer-modified silica adsorbents had higher amine
      content and larger surface area than the aminopropyl-grafted silica adsorbent and
      displayed higher thermal stability than the other polymer-modified silica
      materials previously reported. The CO(2) adsorption/desorption experiments
      performed at 25 degrees C by TGA-DSC method showed that the highest CO(2)
      adsorption capacity (0.98 mmol/g) was observed for the polymer-impregnated silica
      adsorbent. CO(2) adsorbed on all samples was completely desorbed by purging with
      inert gas at 60 degrees C except for the aminopropyl-grafted silica material,
      which showed the highest enthalpy of CO(2) adsorption.

PMID- 22621913
TI  - Boundary lubrication by sodium salts: a Hofmeister series effect.
AB  - Boundary lubrication plays an important role in the function of sliding surfaces
      in contact. Of particular interest in this study, boundary regime tribology is
      relevant for understanding textural attributes perceived during oral consumption
      of food, where the tongue squeezes and slides against the hard palate. This work
      investigates aqueous lubrication of a sliding/rolling ball-on-disc contact by
      sodium anions of the Hofmeister series in both water and guar gum solutions. Low
      concentrations (0.001 M) of strongly kosmotropic salts provide reduced friction
      coefficients in both systems (water and guar gum solutions), although a different
      mechanism prevails in each. Surface-bound hydrated ions are responsible in the
      case of water, and salt-promoted adsorption of hydrated-polymer chains dominate
      with guar gum. In each system, friction decreases in accordance with the
      Hofmeister series: iodide, nitrate, bromide, chloride, fluoride, phosphate and
      citrate. The addition of salt has little impact on solution of bulk viscosity,
      and so this work demonstrates that significant boundary lubrication can be
      provided without surface modification and with lubricants of viscosity similar to
      that of water.

PMID- 22621914
TI  - In vitro activities of ceftobiprole, dalbavancin, daptomycin, linezolid, and
      tigecycline against methicillin-resistant Staphylococcus aureus blood isolates:
      stratified analysis by vancomycin MIC.
AB  - The in vitro activities of newer agents against 569 methicillin-resistant
      Staphylococcus aureus (MRSA) blood isolates stratified by vancomycin MIC values
      (<=1 versus >1 MUg/mL) were evaluated using broth microdilution methods. All
      agents had good in vitro activities against MRSA regardless of vancomycin MIC
      values. Some significant correlations between vancomycin and newer agents' MIC
      values were observed.

PMID- 22621915
TI  - Food intake monitoring: an acoustical approach to automated food intake activity
      detection and classification of consumed food.
AB  - Obesity and nutrition-related diseases are currently growing challenges for
      medicine. A precise and timesaving method for food intake monitoring is needed.
      For this purpose, an approach based on the classification of sounds produced
      during food intake is presented. Sounds are recorded non-invasively by miniature
      microphones in the outer ear canal. A database of 51 participants eating seven
      types of food and consuming one drink has been developed for algorithm
      development and model training. The database is labeled manually using a protocol
      with introductions for annotation. The annotation procedure is evaluated using
      Cohen's kappa coefficient. The food intake activity is detected by the comparison
      of the signal energy of in-ear sounds to environmental sounds recorded by a
      reference microphone. Hidden Markov models are used for the recognition of single
      chew or swallowing events. Intake cycles are modeled as event sequences in finite
      state grammars. Classification of consumed food is realized by a finite-state
      grammar decoder based on the Viterbi algorithm. We achieved a detection accuracy
      of 83% and a food classification accuracy of 79% on a test set of 10% of all
      records. Our approach faces the need of monitoring the time and occurrence of
      eating. With differentiation of consumed food, a first step toward the goal of
      meal weight estimation is taken.

PMID- 22621916
TI  - Alerting network dysfunction in early multiple sclerosis.
AB  - The objective of this study is to assess attention in recently diagnosed
      relapsing-remitting multiple sclerosis patients. Twenty-seven patients with early
      multiple sclerosis and low clinical disability scores (EDSS<2) and 27 sex-, age-,
      and education-matched healthy controls underwent attention assessment using the
      Attentional Network Test, a computerized task designed to measure efficiency
      independently in 3 attentional networks (Alerting, Orienting and Executive
      Control). MS patients had significantly less efficiency in the Alerting network
      (p = .006). In contrast, in the Orienting and Executive Control networks, they
      did not differ from controls. A significant interaction between Alerting and
      Executive Control was also found in the MS patients (p = .007). Early relapsing
      remitting multiple sclerosis particularly affects the Alerting domain of
      attention, whereas the Orienting and Executive Control domains are not affected.

PMID- 22621917
TI  - Dual-energy CT can evaluate both hilar and mediastinal lymph nodes and lesion
      vascularity with a single scan at 60 seconds after contrast medium injection.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to investigate whether 80-kVp
      and weighted-average 120-kVp computed tomographic (CT) images scanned at 60
      seconds after contrast material injection using a dual-source CT scanner could
      substitute for conventional 120-kVp images obtained at 30 and 100 seconds.
      MATERIALS AND METHODS: Eighty-three consecutive patients with suspected lung
      cancer were enrolled. Images were obtained in dual-energy mode (80 and 140 kVp)
      at 60 seconds and conventional 120-kVp mode at 30 and 100 seconds after contrast
      injection. The CT numbers of the pulmonary artery, pulmonary vein, hilar zone
      lymph nodes, and pulmonary lesions were measured. Contrasts between the pulmonary
      artery/pulmonary vein and lymph nodes and beam-hardening artifacts were visually
      evaluated using five-point and four-point scales, respectively. The degree of
      enhancement was evaluated on 30-second 120-kVp, 100-second 120-kVp, and 60-second
      weighted-average 120-kVp images. RESULTS: The mean differences in attenuation
      between the pulmonary artery/pulmonary vein and lymph nodes on the 30-second 120
      kVp, 60-second 80-kVp, and 60-second weighted-average 120-kVp images were
      184/155, 130/140, and 84/92 Hounsfield units, respectively (all P values <.001).
      The mean contrast scores for the hilar/mediastinal lymph nodes were 4.5/4.7,
      3.7/4.2, 3.3/3.6, and 2.4/2.5 for these three and for 100-second 120-kVp images,
      respectively (all P values <.01). The mean artifact scores of the four images
      were 1.2, 3.4, 3.6, and 4.0, respectively. On 60-second weighted-average 120-kVp
      images, 55 of 60 lesions (92%) showed higher enhancement than on 100-second
      conventional 120-kVp images. CONCLUSIONS: Dual-energy CT images scanned 60
      seconds after contrast injection show excellent vessel-lymph node contrast and
      enhancement of lesions and can replace dual-phase scan protocols.

PMID- 22621918
TI  - The effect of levofloxacin and moxifloxacin on cardiovascular functions of rats
      with streptozotocin-induced diabetes.
AB  - Fluoroquinolone antibiotics cause rare, but clinically important, adverse events
      including hyperglycaemia and hypoglycaemia. The present study focuses on the
      possible effect of levofloxacin and moxifloxacin on the cardiovascular functions
      of rats with type I diabetes. Both antibiotics caused bradycardia. Levofloxacin
      but not moxifloxacin caused hypoglycaemia in diabetic rats and an increase in
      amplitude of the ST segment revealed by electrocardiogram (ECG) analysis of
      isolated hearts. In pressurized mesenteric arteries, levofloxacin did not affect
      the endothelium-derived hyperpolarising factor (EDHF) pathway or its main
      components, the small-conductance Ca(2+) activated potassium (SK(Ca)) and
      intermediate-conductance Ca(2+) activated potassium (IK(Ca)) channels. In
      moxifloxacin-treated rats, an increase in the EDHF response was observed, which
      was largely attributed to SK(Ca)-activation. In conclusion, levofloxacin and
      moxifloxacin use appeared to vary but with no evidence of impairment of the
      cardiovascular function. However, it is still possible that these antibiotics may
      produce different effects if there are co-morbidities and therefore their use
      must be with care.

PMID- 22621919
TI  - Non-invasive assessment of microcirculation by sidestream dark field imaging as a
      marker of coronary artery disease in diabetes.
AB  - PURPOSE: In diabetes, generalised microvascular disease and coronary artery
      disease (CAD) are likely to occur in parallel. We used a sidestream dark field
      (SDF) handheld imaging device to determine the relation between the labial
      microcirculation parameters and CAD in asymptomatic patients with diabetes.
      METHODS: SDF imaging was validated for assessment of labial capillary density and
      tortuosity. Thereafter, mean labial capillary density and tortuosity were
      evaluated and compared in non-diabetic controls, and in asymptomatic patients
      with type 1 and type 2 diabetes. In diabetic patients, mean capillary density and
      tortuosity were compared according to the presence of CAD. RESULTS: Both type 1
      and type 2 diabetes were associated with increased capillary density and
      tortuosity. In diabetes, mean capillary density was an independent predictor of
      elevated coronary artery calcium (CAC) (p = 0.03) and obstructive CAD on computed
      tomography angiography (p = 0.01). Using a cut-off mean capillary density of 24.9
      (per 0.63 mm(2)) the negative predictive value was 84% and 89% for elevated CAC
      and obstructive CAD. Likewise, capillary tortuosity was an independent predictor
      of increased CAC (p = 0.01) and obstructive CAD (p = 0.04). CONCLUSION:
      Assessment of labial microcirculation parameters using SDF imaging is feasible
      and conveys the potential to estimate vascular morbidity in patients with
      diabetes, at bedside.

PMID- 22621920
TI  - ATP depletion triggers acute myeloid leukemia differentiation through an ATR/Chk1
      protein-dependent and p53 protein-independent pathway.
AB  - Despite advances in oncology drug development, most commonly used cancer
      therapeutics exhibit serious adverse effects. Often the toxicities of
      chemotherapeutics are due to the induction of significant DNA damage that is
      necessary for their ability to kill cancer cells. In some clinical situations,
      the direct induction of significant cytotoxicity is not a requirement to meet
      clinical goals. For example, differentiation, growth arrest, and/or senescence is
      a valuable outcome in some cases. In fact, in the case of acute myeloid leukemia
      (AML), the use of the differentiation agent all-trans-retinoic acid (ATRA) has
      revolutionized the therapy for a subset of leukemia patients and led to a
      dramatic survival improvement. Remarkably, this therapeutic approach is possible
      even in many elderly patients, who would not be able to tolerate therapy with
      traditional cytotoxic chemotherapy. Because of the success of ATRA, there is
      widespread interest in identifying differentiation strategies that may be
      effective for the 90-95% of AML patients who do not clinically respond to ATRA.
      Utilizing an AML differentiation agent that is in development, we found that AML
      differentiation can be induced through ATP depletion and the subsequent
      activation of DNA damage signaling through an ATR/Chk1-dependent and p53
      independent pathway. This study not only reveals mechanisms of AML
      differentiation but also suggests that further investigation is warranted to
      investigate the potential clinical use of low dose chemotherapeutics to induce
      differentiation instead of cytotoxicity. This therapeutic approach may be of
      particular benefit to patients, such as elderly AML patients, who often cannot
      tolerate traditional AML chemotherapy.

PMID- 22621921
TI  - Disintegration of nascent replication bubbles during thymine starvation triggers
      RecA- and RecBCD-dependent replication origin destruction.
AB  - Thymineless death strikes cells unable to synthesize DNA precursor dTTP, with the
      nature of chromosomal damage still unclear. Thymine starvation stalls replication
      forks, whereas accumulating evidence indicates the replication origin is also
      affected. Using a novel DNA labeling technique, here we show that replication
      slowly continues in thymine-starved cells, but the newly synthesized DNA becomes
      fragmented and degraded. This degradation apparently releases enough thymine to
      sustain initiation of new replication bubbles from the chromosomal origin, which
      destabilizes the origin in a RecA-dependent manner. Marker frequency analysis
      with gene arrays 1) reveals destruction of the origin-centered chromosomal
      segment in RecA(+) cells; 2) confirms origin accumulation in the recA mutants;
      and 3) identifies the sites around the origin where destruction initiates in the
      recBCD mutants. We propose that thymineless cells convert persistent single
      strand gaps behind replication forks into double-strand breaks, using the
      released thymine for new initiations, whereas subsequent disintegration of small
      replication bubbles causes replication origin destruction.

PMID- 22621922
TI  - Vaccinia-related kinase 1 (VRK1) is an upstream nucleosomal kinase required for
      the assembly of 53BP1 foci in response to ionizing radiation-induced DNA damage.
AB  - Cellular responses to DNA damage require the formation of protein complexes in a
      highly organized fashion. The complete molecular components that participate in
      the sequential signaling response to DNA damage remain unknown. Here we
      demonstrate that vaccinia-related kinase 1 (VRK1) in resting cells plays an
      important role in the formation of ionizing radiation-induced foci that assemble
      on the 53BP1 scaffold protein during the DNA damage response. The kinase VRK1 is
      activated by DNA double strand breaks induced by ionizing radiation (IR) and
      specifically phosphorylates 53BP1 in serum-starved cells. VRK1 knockdown resulted
      in the defective formation of 53BP1 foci in response to IR both in number and
      size. This observed effect on 53BP1 foci is p53- and ataxia-telangiectasia
      mutated (ATM)-independent and can be rescued with VRK1 mutants resistant to
      siRNA. VRK1 knockdown also prevented the activating phosphorylation of ATM, CHK2,
      and DNA-dependent protein kinase in response to IR. VRK1 activation in response
      to DNA damage is a novel and early step in the signaling of mammalian DNA damage
      responses.

PMID- 22621923
TI  - Insulin resistance and metabolic derangements in obese mice are ameliorated by a
      novel peroxisome proliferator-activated receptor gamma-sparing thiazolidinedione.
AB  - Currently approved thiazolidinediones (TZDs) are effective insulin-sensitizing
      drugs that may have efficacy for treatment of a variety of metabolic and
      inflammatory diseases, but their use is limited by side effects that are mediated
      through ectopic activation of the peroxisome proliferator-activated receptor
      gamma (PPARgamma). Emerging evidence suggests that the potent anti-diabetic
      efficacy of TZDs can be separated from the ability to serve as ligands for
      PPARgamma. A novel TZD analog (MSDC-0602) with very low affinity for binding and
      activation of PPARgamma was evaluated for its effects on insulin resistance in
      obese mice. MSDC-0602 treatment markedly improved several measures of multiorgan
      insulin sensitivity, adipose tissue inflammation, and hepatic metabolic
      derangements, including suppressing hepatic lipogenesis and gluconeogenesis.
      These beneficial effects were mediated at least in part via direct actions on
      hepatocytes and were preserved in hepatocytes from liver-specific PPARgamma(-/-)
      mice, indicating that PPARgamma was not required to suppress these pathways. In
      conclusion, the beneficial pharmacology exhibited by MSDC-0602 on insulin
      sensitivity suggests that PPARgamma-sparing TZDs are effective for treatment of
      type 2 diabetes with reduced risk of PPARgamma-mediated side effects.

PMID- 22621924
TI  - Reduction of all-trans-retinal in vertebrate rod photoreceptors requires the
      combined action of RDH8 and RDH12.
AB  - In vertebrate rod cells, retinoid dehydrogenases/reductases (RDHs) are critical
      for reducing the reactive aldehyde all-trans-retinal that is released by
      photoactivated rhodopsin, to all-trans-retinol (vitamin A). Previous studies have
      shown that RDH8 localizes to photoreceptor outer segments and is a strong
      candidate for performing this role. However, RDH12 function in the photoreceptor
      inner segments is also key, because loss of function mutations cause retinal
      degeneration in some forms of Leber congenital amaurosis. To investigate the in
      vivo roles of RDH8 and RDH12, we used fluorescence imaging to examine all-trans
      retinol production in single isolated rod cells from wild-type mice and knock-out
      mice lacking either one or both RDHs. Outer segments of rods deficient in Rdh8
      failed to reduce all-trans-retinal, but those deficient in Rdh12 were unaffected.
      Following exposure to light, a leak of retinoids from outer to inner segments was
      detected in rods from both wild-type and knock-out mice. In cells lacking Rdh8 or
      Rdh12, this leak was mainly all-trans-retinal. Wild-type rods incubated with all
      trans-retinal reduced moderate loads of retinal within the cell interior, but
      this ability was lost by cells deficient in Rdh8 or Rdh12. Our findings are
      consistent with localization of RDH8 to the outer segment where it provides most
      of the activity needed to reduce all-trans-retinal generated by the light
      response. In contrast, RDH12 in inner segments can protect vital cell organelles
      against aldehyde toxicity caused by an intracellular leak of all-trans-retinal,
      as well as other aldehydes originating both inside and outside the cell.

PMID- 22621925
TI  - Complex cisplatin-double strand break (DSB) lesions directly impair cellular non
      homologous end-joining (NHEJ) independent of downstream damage response (DDR)
      pathways.
AB  - The treatment for advanced stage non-small cell lung cancer (NSCLC) often
      includes platinum-based chemotherapy and IR. Cisplatin and IR combination therapy
      display schedule and dose-dependent synergy, the mechanism of which is not
      completely understood. In a series of in vitro and cell culture assays in a NSCLC
      model, we investigated both the downstream and direct treatment and damage
      effects of cisplatin on NHEJ catalyzed repair of a DNA DSB. The results
      demonstrate that extracts prepared from cisplatin-treated cells are fully capable
      of NHEJ catalyzed repair of a DSB using a non-cisplatin-damaged DNA substrate in
      vitro. Similarly, using two different host cell reactivation assays, treatment of
      cells prior to transfection of a linear, undamaged reporter plasmid revealed no
      reduction in NHEJ compared with untreated cells. In contrast, transfection of a
      linear GFP-reporter plasmid containing site-specific, cisplatin lesions 6-bp from
      the termini revealed a significant impairment in DSB repair of the cisplatin
      damaged DNA substrates in the absence of cellular treatment with cisplatin.
      Together, these data demonstrate that impaired NHEJ in combined cisplatin-IR
      treated cells is likely the result of a direct effect of cisplatin-DNA lesions
      near a DSB and that the indirect cellular effects of cisplatin treatment are not
      significant contributors to the synergistic cytotoxicity observed with
      combination cisplatin-IR treatment.

PMID- 22621926
TI  - The small hydrophobic protein of the human respiratory syncytial virus forms
      pentameric ion channels.
AB  - The small hydrophobic (SH) protein is encoded by the human respiratory syncytial
      virus. Its absence leads to viral attenuation in the context of whole organisms,
      and it prevents apoptosis in infected cells. Herein, we have examined the
      structure of SH protein in detergent micelles and in lipid bilayers, by solution
      NMR and attenuated total reflection-Fourier transform infrared spectroscopy,
      respectively. We found that SH protein has a single alpha-helical transmembrane
      domain and forms homopentamers in several detergents. In detergent micelles, the
      transmembrane domain is flanked N-terminally by an alpha-helix that forms a ring
      around the lumen of the pore and C-terminally by an extended beta-turn. SH
      protein was found in the plasma membrane of transiently expressing HEK 293 cells,
      which showed pH-dependent (acid-activated) channel activity. Channel activity was
      abolished in mutants lacking both native His residues, His(22) and His(51), but
      not when either His was present. Herein, we propose that the pentameric model of
      SH protein presented is a physiologically relevant conformation, albeit probably
      not the only one, in which SH contributes to RSV infection and replication.
      Viroporins are short (~100 amino acids) viral membrane proteins that form
      oligomers of a defined size, act as proton or ion channels, and in general
      enhance membrane permeability in the host. However, with some exceptions, their
      precise biological role of their channel activity is not understood. In general,
      viroporins resemble poorly specialized proteins but are nevertheless critical for
      viral fitness. In vivo, viruses lacking viroporins usually exhibit an attenuated
      or weakened phenotype, altered tropism, and diminished pathological effects. We
      have chosen to study the SH protein, 64 amino acids long, found in the human
      respiratory syncytial virus because of the effect of RSV on human health and the
      lack of adequate antivirals. We show that SH protein forms oligomers that behave
      as ion channels when activated at low pH. This study adds SH protein to a growing
      group of viroporins that have been structurally characterized. Although the
      precise biological role of this pentameric channel is still unknown, this report
      is nevertheless essential to fill some of the many gaps that exist in the
      understanding of SH protein function.

PMID- 22621927
TI  - SWI/SNF protein component BAF250a regulates cardiac progenitor cell
      differentiation by modulating chromatin accessibility during second heart field
      development.
AB  - ATP-dependent SWI/SNF chromatin remodeling complexes alter the structure of
      chromatin at specific loci and facilitate tissue-specific gene regulation during
      development. Several SWI/SNF subunits are required for cardiogenesis. However,
      the function and mechanisms of SWI/SNF in mediating cardiac progenitor cell (CPC)
      differentiation during cardiogenesis are not well understood. Our studies of the
      SWI/SNF chromatin remodeling complex identified that BAF250a, a regulatory
      subunit of the SWI/SNF, plays a key role in CPC differentiation. BAF250a ablation
      in mouse second heart field (SHF) led to trabeculation defects in the right
      ventricle, ventricular septal defect, persistent truncus arteriosus, reduced
      myocardial proliferation, and embryonic lethality around E13. Using an embryonic
      stem cell culture system that models the formation and differentiation of SHF
      CPCs in vivo, we have shown that BAF250a ablation in CPCs specifically inhibits
      cardiomyocyte formation. Moreover, BAF250a selectively regulates the expression
      of key cardiac factors Mef2c, Nkx2.5, and Bmp10 in SHF CPCs. Chromatin
      immunoprecipitation and DNase I digestion assays indicate that BAF250a regulates
      gene expression by binding selectively to its target gene promoters and
      recruiting Brg1, the catalytic subunit of SWI/SNF, to modulate chromatin
      accessibility. Our results thus identify BAF250a-mediated chromatin remodeling as
      an essential epigenetic mechanism mediating CPC differentiation.

PMID- 22621928
TI  - ATP-dependent RecG helicase is required for the transcriptional regulator OxyR
      function in Pseudomonas species.
AB  - The oxyR gene appears to reside in an operon with the recG helicase gene in many
      bacteria, including pathogenic Pseudomonas aeruginosa and Pseudomonas putida.
      Analysis of P. putida transcriptomes shows that many OxyR-controlled genes are
      regulated by the ATP-dependent RecG helicase and that RecG alone modulates the
      expression of many genes. We found that purified RecG binds to the promoters of
      many OxyR-controlled genes and that expression of these genes was not induced
      under conditions of oxidative stress in recG mutants of P. aeruginosa, P. putida,
      and Escherichia coli. In vitro data revealed that promoters containing
      palindromic sequences are essential for RecG binding and that single-strand
      binding proteins and ATP are also needed for RecG to promote transcription,
      whereas a magnesium ion has the opposite effect. The OxyR tetramer preferentially
      binds to promoters after RecG has generated linear DNA in the presence of ATP;
      otherwise, the OxyR dimer has higher affinity. This study provides new insights
      into the mechanism of bacterial transcription by demonstrating that RecG might be
      required for the induction of the OxyR regulon by unwinding palindromic DNA for
      transcription. This work describes a novel bacterial transcriptional function by
      RecG helicase with OxyR and may provide new targets for controlling Pseudomonas
      species pathogen.

PMID- 22621929
TI  - The putative GTPase encoded by MTG3 functions in a novel pathway for regulating
      assembly of the small subunit of yeast mitochondrial ribosomes.
AB  - Very little is known about biogenesis of mitochondrial ribosomes. The GTPases
      encoded by the nuclear MTG1 and MTG2 genes of Saccharomyces cerevisiae have been
      reported to play a role in assembly of the ribosomal 54 S subunit. In the present
      study biochemical screens of a collection of respiratory deficient yeast mutants
      have enabled us to identify a third gene essential for expression of
      mitochondrial ribosomes. This gene codes for a member of the YqeH family of
      GTPases, which we have named MTG3 in keeping with the earlier convention.
      Mutations in MTG3 cause the accumulation of the 15 S rRNA precursor, previously
      shown to have an 80-nucleotide 5' extension. Sucrose gradient sedimentation of
      mitochondrial ribosomes from temperature-sensitive mtg3 mutants grown at the
      permissive and restrictive temperatures, combined with immunobloting with subunit
      specific antibodies, indicate that Mtg3p is required for assembly of the 30 S but
      not 54 S ribosomal subunit. The respiratory deficient growth phenotype of an mtg3
      null mutant is partially rescued by overexpression of the Mrpl4p constituent
      located at the peptide exit site of the 54 S subunit. The rescue is accompanied
      by an increase in processed 15 S rRNA. This suggests that Mtg3p and Mrpl4p
      jointly regulate assembly of the small subunit by modulating processing of the 15
      S rRNA precursor.

PMID- 22621930
TI  - Identification of residues that confer sugar selectivity to UDP
      glycosyltransferase 3A (UGT3A) enzymes.
AB  - Recent studies in this laboratory characterized the UGT3A family enzymes, UGT3A1
      and UGT3A2, and showed that neither uses the traditional UDP-glycosyltransferase
      UGT co-substrate UDP-glucuronic acid. Rather, UGT3A1 uses GlcNAc as preferred
      sugar donor and UGT3A2 uses UDP-Glc. The enzymatic characterization of UGT3A
      mutants, structural modeling, and multispecies gene analysis have now been
      employed to identify a residue within the active site of these enzymes that
      confers their unique sugar preferences. An asparagine (Asn-391) in the UGT
      signature sequence of UGT3A1 is necessary for utilization of UDP-GlcNAc.
      Conversely, a phenylalanine (Phe-391) in UGT3A2 favors UDP-Glc use. Mutation of
      Asn-391 to Phe in UGT3A1 enhances its ability to utilize UDP-Glc and completely
      inhibits its ability to use UDP-GlcNAc. An analysis of homology models docked
      with UDP-sugar donors indicates that Asn-391 in UGT3A1 is able to accommodate the
      N-acetyl group on C2 of UDP-GlcNAc so that the anomeric carbon atom (C1) is
      optimally situated for catalysis involving His-35. Replacement of Asn with Phe at
      position 391 disrupts this catalytically productive orientation of UDP-GlcNAc but
      allows a more optimal alignment of UDP-Glc for sugar donation. Multispecies
      sequence analysis reveals that only primates possess UGT3A sequences containing
      Asn-391, suggesting that other mammals may not have the capacity to N
      acetylglucosaminidate small molecules. In support of this hypothesis, Asn-391
      containing UGT3A forms from two non-human primates were found to use UDP-GlcNAc,
      whereas UGT3A isoforms from non-primates could not use this sugar donor. This
      work gives new insight into the residues that confer sugar specificity to UGT
      family members and suggests a primate-specific innovation in glycosidation of
      small molecules.

PMID- 22621931
TI  - Phosphorylation of mycobacterial PcaA inhibits mycolic acid cyclopropanation:
      consequences for intracellular survival and for phagosome maturation block.
AB  - Pathogenic mycobacteria survive within macrophages by residing in phagosomes,
      which they prevent from maturing and fusing with lysosomes. Although several
      bacterial components were seen to modulate phagosome processing, the molecular
      regulatory mechanisms taking part in this process remain elusive. We investigated
      whether the phagosome maturation block (PMB) could be modulated by signaling
      through Ser/Thr phosphorylation. Here, we demonstrated that mycolic acid
      cyclopropane synthase PcaA, but not MmaA2, was phosphorylated by mycobacterial
      Ser/Thr kinases at Thr-168 and Thr-183 both in vitro and in mycobacteria.
      Phosphorylation of PcaA was associated with a significant decrease in the
      methyltransferase activity, in agreement with the strategic structural
      localization of these two phosphoacceptors. Using a BCG DeltapcaA mutant, we
      showed that PcaA was required for intracellular survival and prevention of
      phagosome maturation in human monocyte-derived macrophages. The physiological
      relevance of PcaA phosphorylation was further assessed by generating PcaA
      phosphoablative (T168A/T183A) or phosphomimetic (T168D/T183D) mutants. In
      contrast to the wild-type and phosphoablative pcaA alleles, introduction of the
      phosphomimetic pcaA allele in the DeltapcaA mutant failed to restore the parental
      mycolic acid profile and cording morphotype. Importantly, the PcaA phosphomimetic
      strain, as the DeltapcaA mutant, exhibited reduced survival in human macrophages
      and was unable to prevent phagosome maturation. Our results add new insight into
      the importance of mycolic acid cyclopropane rings in the PMB and provide the
      first evidence of a Ser/Thr kinase-dependent mechanism for modulating mycolic
      acid composition and PMB.

PMID- 22621932
TI  - Transforming growth factor beta1 (TGF-beta1) suppresses growth of B-cell lymphoma
      cells by p14(ARF)-dependent regulation of mutant p53.
AB  - Previously we reported that TGF-beta1-induced growth suppression was associated
      with a decrease in mutant p53 levels in B-cell lymphoma cells. The goal of the
      present study was to understand the mechanism involved in TGF-beta1-mediated down
      regulation of mutant p53. In RL and CA46, two B-cell lymphoma cell lines, TGF
      beta1 treatment caused down-regulation of E2F-1 transcription factor resulting in
      the down-regulation of both p14(ARF) and mutant p53, leading to growth arrest.
      Experimental overexpression of E2F-1 increased p14(ARF) level and blocked TGF
      beta1-induced down-regulation of p14(ARF). Overexpression of p14(ARF) blocked the
      down-regulation of mutant p53 and prevented growth arrest. p14(ARF) also
      attenuated TGF-beta1-induced p21(Cip1/WAF1) induction, which was reversible by
      p53 siRNA, indicating the involvement of mutant p53 in controlling the TGF-beta1
      induced expression of p21(Cip1/WAF1). The interaction observed between phospho
      Smad2 and mutant p53 in the nucleus could be the mechanism responsible for
      blocking the growth-suppressive effects of TGF-beta1. In RL cells, p14(ARF) is
      present in a trimer consisting of mutant p53-Mdm2-p14(ARF) and in a dimer
      consisting of Mdm2-p14(ARF). Because it is known that Mdm2 can degrade p53, it is
      possible that, in its trimeric form, p14(ARF) is able to stabilize mutant p53 by
      inhibiting Mdm2. In its dimeric form, p14(ARF) may be sequestering Mdm2, limiting
      its ability to degrade p53. Collectively, these data demonstrate a unique
      mechanism in which the inhibition of TGF-beta1-mediated growth suppression by
      mutant p53 can be reversed by the down-regulation of its stabilizing protein
      p14(ARF). This work suggests that the high levels of p14(ARF) often found in
      tumor cells could be a potential therapeutic target.

PMID- 22621933
TI  - Crystal structure of the largest subunit of a bacterial RNA-guided immune complex
      and its role in DNA target binding.
AB  - Prokaryotes make use of small RNAs encoded by CRISPR (clustered regularly
      interspaced short palindromic repeat) loci to provide immunity against
      bacteriophage or plasmid invasion. In Escherichia coli, the CRISPR-associated
      complex for antiviral defense (Cascade) utilizes these RNAs to target foreign DNA
      for destruction. CasA, the largest subunit of Cascade, is essential for its
      function. Here we report the crystal structure of Thermus thermophilus CasA. The
      structure is composed of two domains that are arranged in a chair-like
      conformation with a novel fold forming the larger N-terminal domain. Docking of
      the crystal structure into cryo-electron microscopy maps reveals two loops in
      CasA that likely have important functions in DNA target binding. Finally, DNA
      binding experiments show that CasA is essential for binding of Cascade to DNA
      target.

PMID- 22621934
TI  - Auditory and visual differences in time perception? An investigation from a
      developmental perspective with neuropsychological tests.
AB  - Adults and children (5- and 8-year-olds) performed a temporal bisection task with
      either auditory or visual signals and either a short (0.5-1.0s) or long (4.0
      8.0s) duration range. Their working memory and attentional capacities were
      assessed by a series of neuropsychological tests administered in both the
      auditory and visual modalities. Results showed an age-related improvement in the
      ability to discriminate time regardless of the sensory modality and duration.
      However, this improvement was seen to occur more quickly for auditory signals
      than for visual signals and for short durations rather than for long durations.
      The younger children exhibited the poorest ability to discriminate time for long
      durations presented in the visual modality. Statistical analyses of the
      neuropsychological scores revealed that an increase in working memory and
      attentional capacities in the visuospatial modality was the best predictor of age
      related changes in temporal bisection performance for both visual and auditory
      stimuli. In addition, the poorer time sensitivity for visual stimuli than for
      auditory stimuli, especially in the younger children, was explained by the fact
      that the temporal processing of visual stimuli requires more executive attention
      than that of auditory stimuli.

PMID- 22621935
TI  - Bioimpedance of soft tissue under compression.
AB  - In this paper compression-dependent bioimpedance measurements of porcine spleen
      tissue are presented. Using a Cole-Cole model, nonlinear compositional changes in
      extracellular and intracellular makeup; related to a loss of fluid from the
      tissue, are identified during compression. Bioimpedance measurements were made
      using a custom tetrapolar probe and bioimpedance circuitry. As the tissue is
      increasingly compressed up to 50%, both intracellular and extracellular
      resistances increase while bulk membrane capacitance decreases. Increasing
      compression to 80% results in an increase in intracellular resistance and bulk
      membrane capacitance while extracellular resistance decreases. Tissues compressed
      incrementally to 80% show a decreased extracellular resistance of 32%, an
      increased intracellular resistance of 107%, and an increased bulk membrane
      capacitance of 64% compared to their uncompressed values. Intracellular
      resistance exhibits double asymptotic curves when plotted against the peak tissue
      pressure during compression, possibly indicating two distinct phases of
      mechanical change in the tissue during compression. Based on these findings,
      differing theories as to what is happening at a cellular level during high tissue
      compression are discussed, including the possibility of cell rupture and mass
      exudation of cellular material.

PMID- 22621936
TI  - Support for a waiting room time tracker: a survey of patients waiting in an urban
      ED.
AB  - BACKGROUND: Emergency Department (ED) crowding and inpatient boarding lead to
      lengthy wait times for patients, which may cause them to choose to leave without
      being seen. A new initiative to improve communication with patients is to provide
      an estimated wait time with a "time tracker" display, but it is unclear whether
      ED patients would welcome this. OBJECTIVE: To estimate the proportion of ED
      patients who would favor a time tracker display. METHODS: This survey-based study
      was conducted from March to July 2010 at an urban academic center. After being
      triaged, patients were asked to answer a multiple-choice questionnaire, asking
      their preference toward a time tracker display. RESULTS: Of the 375 patients who
      were approached, 340 (91%) participated. Two hundred fourteen of them (63%)
      preferred an ED with a time tracker, 53 (16%) were unsure, and 73 (21%) did not
      prefer an ED with a time tracker. Patients with low-acuity conditions (Emergency
      Severity Index [ESI] 4 or 5) were 1.2 times more likely (95% confidence interval
      1.0-1.4) to favor a time tracker than those with higher acuity (ESI 3).
      Preference was not related to race, age, insurance status, or employment.
      CONCLUSIONS: The majority of patients in our study preferred an ED with a time
      tracker display (63% for vs. 21% against). Support for a time tracker was higher
      among patients triaged with lower ESI levels (4 or 5). A time tracker is viewed
      positively by many patients and may be a beneficial addition in the ED waiting
      room.

PMID- 22621937
TI  - A simple audio-visual prompt device can improve CPR performance.
AB  - BACKGROUND: An adjunct to assist cardiopulmonary resuscitation (CPR) might
      improve the quality of CPR performance. STUDY OBJECTIVES: This study was
      conducted to evaluate whether a simple audio-visual prompt device improves CPR
      performance by emergency medical technicians (EMTs). METHODS: From June 2008 to
      October 2008, 55 EMTs (39 men, mean age 34.9+/-4.8 years) participated in this
      study. A simple audio-visual prompt device was developed. The device generates
      continuous metronomic sounds for chest compression at a rate of 100 beats/min
      with a distinct 30(th) sound followed by two respiration sounds, each for 1
      second. All EMTs were asked to perform a 2-min CPR series on a manikin without
      the device, and one 2-min CPR series with the device. RESULTS: The average rate
      of chest compressions was more accurate when the device was used than when the
      device was not used (101.4+/-12.7 vs. 109.0+/-17.4/min, respectively, p=0.012;
      95% confidence interval [CI] 97.2-103.8 vs. 104.5-113.5/min, respectively), and
      hands-off time during CPR was shorter when the device was used than when the
      device was not used (5.4+/-0.9 vs. 9.2+/-3.9 s, respectively, p<0.001; 95% CI 5.2
      5.7 vs. 8.3-10.3 s, respectively). The mean tidal volume during CPR with the
      device was lower than without the device, resulting in the prevention of
      hyperventilation (477.6+/-60.0 vs. 636.6+/-153.4 mL, respectively, p<0.001; 95%
      CI 463.5-496.2 vs. 607.3-688.9 mL, respectively). CONCLUSION: A simple audio
      visual prompt device can improve CPR performance by emergency medical
      technicians.

PMID- 22621938
TI  - Alternative treatments of pneumothorax.
AB  - BACKGROUND: Pneumothorax has traditionally been treated in the Emergency
      Department by tube thoracostomy. However, this is an invasive procedure with high
      risk of complication and prolonged hospitalization. DISCUSSION: In select
      settings, there are alternative forms of management of pneumothorax that carry
      lower risks and may reduce hospital stay. This article reviews the settings in
      which less invasive treatment, including observation alone, may be indicated.
      This article also reviews the techniques for simple aspiration and small-bore
      catheter insertion (by either Seldinger or catheter-over-wire technique) with
      Heimlich valve, as well as the indications, contraindications, and potential
      risks and benefits of each. CONCLUSIONS: The practices of observation, simple
      aspiration, and small-bore catheter insertion with Heimlich valve for selected
      patients may decrease complications, time, and costs by avoiding invasive
      procedures and hospital admissions.

PMID- 22621939
TI  - Atmospheric fate of poly- and perfluorinated alkyl substances (PFASs): II.
      Emission source strength in summer in Zurich, Switzerland.
AB  - Fluorotelomer alcohols (FTOHs) and perfluorooctane sulfonamides (FOSAs) are
      present in consumer products and are semi-volatile precursors of persistent
      perfluoroalkyl acids (PFAAs). The high variability of levels of FTOHs and FOSAs
      in products makes it difficult to derive FTOH- and FOSA-emissions from urban
      areas based on emission factors. Here we used a multimedia mass balance model
      that describes the day-night cycle of semi-volatile organic chemicals in air to
      interpret measurements of 8:2 FTOH, 10:2 FTOH, MeFOSA and EtFOSA from a sampling
      campaign in summer 2010 in Zurich, Switzerland. The estimated emission source
      strength of the four substances follows the sequence: 8:2 FTOH (2.6 g/h) > 10:2
      FTOH (0.75 g/h) > MeFOSA (0.08 g/h) > EtFOSA (0.05 g/h). There is no FTOHs- or
      FOSAs-related industry in Zurich. Accordingly, our estimates are representative
      of diffusive emissions during use and disposal of consumer products, and describe
      noticeable sources of these PFASs to the environment.

PMID- 22621940
TI  - Neurocognitive speed and inconsistency in Parkinson's disease with and without
      incipient dementia: an 18-month prospective cohort study.
AB  - We examined two-wave longitudinal changes in two indicators of neurocognitive
      speed (i.e., mean rate, intraindividual variability) using one simple and three
      complex reaction time tasks. Participants included idiopathic Parkinson's disease
      (PD) patients, with and without incipient dementia, and normal controls. At
      baseline, there were 45 patients (26 men, 19 women) with idiopathic PD who ranged
      from 65 to 84 years (M = 71.3; SD = 4.5) and 47 matched controls (27 men, 20
      women) who ranged from 65 to 84 years (M = 71.4; SD = 4.9). The 18-month
      longitudinal sample comprised of 74 returning participants (43 controls; 31 PD
      patients) who had no cognitive impairment or dementia at both waves. Ten of the
      31 PD patients returning for Time 3 had dementia or cognitive impairment. These
      constituted the PD with incipient dementia (PDID) group. Repeated measures
      analyses of variance showed that the PD and PDID groups were slower over time on
      the reaction time tasks, whereas the controls improved their performance over
      time on all tasks. Inconsistency distinguished the two clinical groups (i.e., the
      PDID group but not the PD group became more inconsistent over time). Changes in
      neurocognitive speed and inconsistency may be valid clinical markers of PDID.

PMID- 22621941
TI  - The effect of transcutaneous vagus nerve stimulation on pain perception--an
      experimental study.
AB  - BACKGROUND: Recent preclinical work strongly suggests that vagus nerve
      stimulation efficiently modulates nociception and pain processing in humans. Most
      recently, a medical device has offered a transcutaneous electrical stimulation of
      the auricular branch of the vagus nerve (t-VNS) without any surgery. OBJECTIVE:
      Our study investigates whether t-VNS may have the potential to alter pain
      processing using a controlled design. METHODS: Different submodalities of the
      somatosensory system were assessed with quantitative sensory testing (QST)
      including a tonic heat pain paradigm in 48 healthy volunteers. Each subject
      participated in two experimental sessions with active t-VNS (stimulation) or sham
      t-VNS (no stimulation) on different days in a randomized order (crossed-over).
      One session consisted of two QST measurements on the ipsi- and contralateral
      hand, each before and during 1 h of a continuous t-VNS on the left ear using
      rectangular pulses (250 MUS, 25 Hz). RESULTS: We found an increase of mechanical
      and pressure pain threshold and a reduction of mechanical pain sensitivity.
      Moreover, active t-VNS significantly reduced pain ratings during sustained
      application of painful heat for 5 min compared to sham condition. No relevant
      alterations of cardiac or breathing activity or clinical relevant side effects
      were observed during t-VNS. CONCLUSIONS: Our findings of a reduced sensitivity of
      mechanically evoked pain and an inhibition of temporal summation of noxious tonic
      heat in healthy volunteers may pave the way for future studies on patients with
      chronic pain addressing the potential analgesic effects of t-VNS under clinical
      conditions.

PMID- 22621943
TI  - Peripheral primitive neuroectodermal tumor in a two-year-old paint horse.
AB  - A 2-year-old gelding presented with a history of lethargy and anorexia. Physical
      examination revealed pleural and abdominal fluid, as well as several masses in
      the scrotum. The horse became acutely dyspneic despite 7 days of supportive care.
      Because of the poor prognosis, the owners elected euthanasia. Gross necropsy
      findings included multiple masses in the scrotum and inguinal canals and along
      the dorsal peritoneal cavity. The neoplasm infiltrated the kidneys, liver,
      spleen, mesenteric lymph nodes, mesentery, and abdominal surface of the
      diaphragm. Histologically, the neoplasm is composed of spindle to round cells
      arranged in densely cellular areas, vague streams, and rare rosettes. Neoplastic
      cells were immunoreactive for S-100 protein, glial fibrillary acidic protein,
      neuron-specific enolase, neurofilament protein, and synaptophysin. Based on
      gross, histological, and immunohistochemical findings, a diagnosis of peripheral
      primitive neuroectodermal tumor was made. Primitive neuroectodermal tumors are
      rarely described in horses that were associated with the eyes.

PMID- 22621942
TI  - High frequency stimulation can suppress globally seizures induced by 4-AP in the
      rat hippocampus: an acute in vivo study.
AB  - BACKGROUND: High frequency stimulation (HFS) on the hippocampus can locally
      suppress epileptiform activity in-vitro and decrease seizure frequency in vivo.
      In-vitro HFS on the ventral commissural tract, a novel target, was shown to block
      the axonal conduction and suppress activity in the CA1 and CA3 neuron. OBJECTIVE:
      To study the spatial extent of seizure suppression by HFS applied on the tract
      and focus site in an in vivo experiment. METHODS: Five adult Sprague-Dawley rats
      were used for the study. Six electrodes were placed on the septal, middle, and
      temporal hippocampus bilaterally to simultaneously record seizure activity in the
      entire hippocampus. Seizure activity was induced by injecting 4-aminopyridine (4
      AP) into the right middle part of the hippocampus. Following induction, HFS (100
      Hz) was applied to the tract and the focus site at 100, 300 and 500 MUA. RESULTS:
      The induced seizure activity was dominated by two patterns, high frequency
      spiking and pseudo-periodic spikes. Either tract or focus site stimulation could
      generate suppression of only the pseudo-periodic spikes. The suppression rates
      were dependent on stimulation amplitude (P < 0.005, chi square test). However,
      HFS also caused conversion of the seizure pattern. The conversion rates increased
      with higher stimulation amplitudes and were higher with focus site stimulation (P
      < 0.01, Fisher's exact test). CONCLUSIONS: The results of this study have two
      practical implications [1], both tract and focus site stimulation can produce
      global suppression of hippocampus and [2] the choice of stimulation parameters is
      critical in order to produce suppression, but not conversion, of seizure pattern.

PMID- 22621944
TI  - Development and evaluation of a multiplex enzyme-linked immunosorbent assay for
      the detection of antibodies to bovine respiratory diseases on the Meso Scale
      Discovery platform.
AB  - A multiplex enzyme-linked immunosorbent assay (ELISA) to detect antibodies to
      Bovine viral diarrhea virus (BVDV), Bovine herpesvirus 1 (BHV-1), Bovine
      parainfluenza virus 3 (BPV-3), and Bovine respiratory syncytial virus (BRSV) was
      developed on the commercially available Meso Scale Discovery (MSD) platform. The
      multiplex ELISA used the same antigens (relatively crude lysates of cultured
      virus) that are used in the current in-house separate ELISAs. Testing a panel of
      field samples demonstrated the multiplex assay could simultaneously detect the
      presence of several antibodies in a single assay and that there was good
      agreement between the multiplex ELISA and the in-house ELISAs. The use of a
      multiplex ELISA could offer significant benefits for routine serological testing
      through reduced staff time, reduced reagent cost, and streamlined laboratory
      operation.

PMID- 22621945
TI  - Infiltrative gastric adenocarcinoma in a chinchilla (Chinchilla lanigera).
AB  - A case of infiltrative gastric adenocarcinoma in a 5-year-old female chinchilla
      (Chinchilla lanigera) is described. The animal died after a 5-day period of
      lethargy and anorexia. Gross examination revealed increased gastric volume. The
      gastric wall was thickened and contained numerous firm, white nodules on the
      serosal surface. The lumen was obliterated by a firm mass and large amount of
      white, mucous secretion. Numerous white, irregular plaques and nodules were
      observed on the mesentery, visceral surface of the diaphragm, renal capsule, and
      uterine serosa (implantation metastases). Histopathological examination revealed
      an infiltrative gastric adenocarcinoma composed of neoplastic cells organized in
      a gland-like pattern interspersed with connective tissue. Neoplastic cells
      infiltrated the lamina propria, submucosa, and muscular layers, and were positive
      for cytokeratin. Detection of Helicobacter spp. in the gastric mucosa failed
      using Warthin-Starry and Steiner silver stains or immunohistochemistry, but a
      Helicobacter-specific nested polymerase chain reaction followed by sequencing was
      positive for Helicobacter pylori and showed more than 99% similarity to the 16S
      ribosomal RNA gene.

PMID- 22621946
TI  - Antigen-capture enzyme-linked immunosorbent assays for detection of different H5
      avian Influenza A virus.
AB  - Avian Influenza A virus (AIV) subtype H5 is divided into American and Eurasian
      lineages, according to hemagglutinin gene sequences. Although methods for
      detecting H5 AIVs have been described, no H5 strain-specific detection method has
      been reported. The purpose of the present study was to develop an antigen-capture
      enzyme-linked immunosorbent assay (ACE) to detect and differentiate between the
      American and the Eurasian H5 AIVs. Monoclonal antibodies (mAbs) against the HA
      fragment of a Eurasian H5N2 AIV were used as the capture antibodies as well as
      the detector antibodies after labeling with horseradish peroxidase to develop an
      ACE. One mAb was selected for detecting the American as well as the Eurasian H5
      AIVs. The other mAb was used for detecting only the Eurasian H5N2 but not the
      American H5N2 AIVs, H6N1 AIVs, or Newcastle disease virus. The ACEs developed
      would be useful for detection and differentiation of H5 AIVs from the Eurasian
      and the American H5 AIVs.

PMID- 22621947
TI  - Evaluation of a real-time polymerase chain reaction assay for Pseudorabies virus
      surveillance purposes.
AB  - Pseudorabies virus (PRV) is the cause of Aujeszky's disease, a disease that is
      significant economically for the swine industry worldwide. A real-time polymerase
      chain reaction (PCR) assay based on the gB and gE genes was used to identify PRV
      nucleic acid in diagnostic samples. Using virus isolation (VI) as the gold
      standard, the PCR assay performed well in a variety of diagnostic matrices.
      Testing was conducted on 1,027 nasal swabs with the following findings: gB
      sensitivity: 94.6% (95% confidence interval [CI]: 92.3-96.4%), specificity: 71.0%
      (95% CI: 64.0-77.3%); gE sensitivity: 94.6% (95% CI: 92.3-96.4%), specificity:
      79.3% (95% CI: 72.9-84.7%). Diagnostic performance of the real-time PCR assay
      developed as a testing method indicates that it is a rapid, accurate assay that
      can provide reliable results on clinical samples.

PMID- 22621948
TI  - Development of a Bovine leukemia virus polymerase gene-based real-time polymerase
      chain reaction and comparison with an envelope gene-based assay.
AB  - Bovine leukemia virus (BLV) causes a persistent infection with provirus formation
      in B-lymphocytes. A real-time polymerase chain reaction (PCR) based on the
      conserved BLV polymerase (BLV pol) gene sequences was developed. Dually labeled
      probes were used to permit detection by the 5' exonuclease assay. The assay was
      validated with 350 samples of bovine peripheral blood mononuclear cells including
      144 samples from BLV-seropositive animals worldwide (South America, Europe,
      Middle East, Australia) representing 5 of the recently described 7 BLV envelope
      based genotypes. The BLV pol real-time PCR proved to be highly specific and
      sensitive with the detection of up to 1 copy of an internal control plasmid. The
      95% confidence intervals for assay sensitivity and specificity were >= 98.27% and
      >= 98.33%, respectively. Restriction fragment length polymorphism and
      phylogenetic BLV pol-based sequence analysis of the investigated samples were
      performed and compared with the previous described BLV env-based genotypes.
      Grouping of the sequences based on the pol gene yielded similar results as the
      env gene-based assay.

PMID- 22621949
TI  - Isolation of Equine rhinitis A virus from a horse semen sample.
AB  - Semen from an apparently healthy 4-year-old American Quarter Horse was submitted
      to the National Veterinary Services Laboratories for Equine arteritis virus
      isolation. Visual inspection of the semen sample upon arrival noted it was
      unusually yellow in color. The semen sample was inoculated onto cell monolayers,
      and cytopathic effect was observed 5 days postinoculation. The resultant isolate
      tested negative for Equine arteritis virus, and was subsequently identified as
      Equine rhinitis A virus. Equine rhinitis A virus has been isolated from horse
      urine, but has not been described in stallion semen. The present study documents
      the isolation of Equine rhinitis A virus from stallion semen that was likely
      contaminated with urine at the time of collection.

PMID- 22621950
TI  - Association of canine splenic hemangiosarcomas and hematomas with nodular
      lymphoid hyperplasia or siderotic nodules.
AB  - Hemorrhagic splenic masses diagnosed as hemangioma or hemangiosarcoma were
      reviewed. Lymphoid hyperplasia was present in none of the hemangiosarcoma cases
      and in 27% of the hematoma cases. Siderotic nodules in the capsule or trabeculae
      were present in 25% of hemangiosarcoma cases and in 36% of hematoma cases.
      Hemoabdomen was noted in the clinical history of 54% of hemangiosarcoma cases and
      in 22% of hematoma cases. The average age (10.3 and 9.6 years, respectively), sex
      ratios (slightly more males), and most common breeds (Labrador Retriever, Golden
      Retriever, and German Shepherd Dog) were similar for the hemangiosarcoma and
      hematoma cases. Since lymphoid hyperplasia is much more common in cases of
      hematoma, the presence of this feature lends support to a diagnosis of hematoma
      rather than hemangiosarcoma. Signalment, history of hemoabdomen, and presence of
      siderotic nodules do not point to one diagnosis over the other.

PMID- 22621951
TI  - Molecular epidemiology of Mannheimia haemolytica and Mannheimia glucosida
      associated with ovine mastitis.
AB  - While Mannheimia haemolytica and Mannheimia glucosida have been recognized as
      causes of intramammary infection in sheep, there has been no investigation of the
      epidemiology of the strains involved. Pulsed field gel electrophoresis was used
      to study the molecular epidemiology of isolates of these 2 species associated
      with ovine mastitis. Ten distinct strains were recognized among 12 M. haemolytica
      isolates, and 7 distinct strains among 13 M. glucosida isolates. The results
      demonstrate a high diversity of isolates with the ability to cause ovine
      mastitis. However, the presence of some identical isolates may suggest the
      possibility of horizontal transmission of these species in some flocks, possibly
      through lamb sucking, and/or differences in the capacity of some isolates to
      cause mastitis in sheep.

PMID- 22621952
TI  - Detection of prion protein in the cerebrospinal fluid of elk (Cervus canadensis
      nelsoni) with chronic wasting disease using protein misfolding cyclic
      amplification.
AB  - Cerebrospinal fluid (CSF) has been examined as a possible source for preclinical
      diagnosis of prion diseases in hamsters and sheep. The present report describes
      the detection of chronic wasting disease (CWD) in the CSF of elk and evaluates
      its usefulness as an antemortem test for CWD. The CSF from 6 captive and 31 free
      ranging adult elk was collected at necropsy and evaluated for the presence of the
      abnormal isoform of the prion protein that has been associated with CWD
      (PrP(CWD)) via protein misfolding cyclic amplification. Additionally, the obex
      from each animal was examined by immunohistochemistry (IHC). Four out of 6
      captive animals were CWD-positive and euthanized due to signs of terminal CWD.
      The remaining 2 were CWD negative. None of the 31 free-range animals showed overt
      signs of CWD, but 12 out of 31 tested positive for CWD by IHC. Protein misfolding
      cyclic amplification detected PrP(CWD) from 3 of the 4 captive animals showing
      clinical signs of CWD and none of the nonclinical animals that were CWD positive
      by IHC. The data suggests that CWD prions can be detected in the CSF of elk, but
      only relatively late in the course of the disease.

PMID- 22621953
TI  - Purification, gene cloning and characterization of an acidic beta-1,4-glucanase
      from Phialophora sp. G5 with potential applications in the brewing and feed
      industries.
AB  - An extracellular beta-1,4-glucanase (CelG5, ~55.0 kDa) was isolated from the
      culture filtrate of Phialophora sp. G5, and its encoding gene was cloned. The
      deduced amino acid sequence of CelG5 was at most 73.6% and 44.0%, respectively,
      identical with a hypothetical protein from Sordaria macrospora and an
      experimentally verified GH 7 endo-beta-1,4-glucanase of Neurospora tetrasperma
      FGSC 2508. Native CelG5 had pH and temperature optima of pH 4.5-5.0 and 55-60
      degrees C. The enzyme showed some properties superior than most fungal beta-1,4
      glucanases, such as high activity over a wide pH range (exhibiting >50% of the
      maximum activity at pH 2.0-7.0), excellent stability in extreme acidic to
      alkaline conditions (pH 2.0-9.0), and strong resistance against pepsin and
      trypsin (retaining 89% and 94% activity, respectively). Recombinant CelG5
      produced in Pichia pastoris had a molecular mass and a pH optimum similar to
      native CelG5, but with maximal activity at 65 degrees C. Application tests showed
      that native CelG5 was stable under simulated gastric conditions (retaining >70%
      activity), and had capacity to decrease the viscosity of barley-bean feed (8.9%
      by 200 U CelG5) and mash (6.1% by 50 U CelG5) and increase the filtration rate of
      mash (18.4% by 50 U CelG5). These properties make CelG5 a good candidate for
      utilization in the animal feed and brewing industries.

PMID- 22621954
TI  - Trichloroethylene and tetrachloroethylene elimination from the air by means of a
      hybrid bioreactor with immobilized biomass.
AB  - Two-phase bioreactors consisting of bacterial consortium in suspension and
      sorbents with immobilized biomass were used to treat waste air containing
      chlorinated ethenes, trichloroethylene (TCE) and tetrachloroethylene (PCE).
      Synthetic municipal sewage was used as the medium for bacterial growth. The
      system was operated with loadings in the range 1.48-4.76 gm(-3)h(-1) for TCE and
      1.49-5.96 gm(-3)h(-1) for PCE. The efficiency of contaminant elimination was 55
      86% in the bioreactor with wood chips and 33-89% in the bioreactor filled with
      zeolite. The best results were observed 1 week after the pollutant loading was
      increased. However, in these conditions, the stability of the process was not
      achieved. In the next 7 days the effectiveness of the system decreased.
      Contaminant removal efficiency, enzymatic activity and the biomass content were
      all diminished. The system was working without being supplied with additional
      hydrocarbons as the growth-supporting substrates. It is assumed that ammonia
      produced during the transformation of wastewater components induced enzymes for
      the cometabolic degradation of TCE and PCE. However, the evaluation of nitrogen
      compound transformations in the system is difficult due to the sorption on
      carriers and the combined processes of nitrification and the aerobic
      denitrification. An applied method of air treatment is advantageous from both
      economic and environmental point of views.

PMID- 22621955
TI  - Development of macrolide lactone antibiotic brefeldin A fermentation process with
      Eupenicillium brefeldianum ZJB082702.
AB  - In this work, a robust brefeldin A-synthesizing fungus, Eupenicillium
      brefeldianum ZJB082702, was bred from a Murraya paniculata endophytic fungus E.
      brefeldianum A1163. Using one-factor-at-a-time experimental design, optimization
      of media composition for E. brefeldianum ZJB082702 fermenting brefeldin A was
      conducted. Outcomes indicated that mixed carbon source and mixed nitrogen source
      were of c ritical importance to brefeldin A fermentation. After 6d culture in the
      optimized fermentation media, composed of (gl(-1)) 13.33 starch, 26.67 glucose,
      1.0 yeast extract powder, 1.0 corn steep liquor, 0.5 soybean meal, 0.75 NaNO(3),
      2.5 malt extract, 6.0 CaCO(3), 3.0 MgSO(4), 4.0 KH(2)PO(4), 1.0 * 10(-2) CuSO(4),
      brefeldin A yield peaked at 1304.7 mgl(-1), 648.2 mgl(-1) in 500 ml baffled flask
      and 15 l stirred fermentor respectively, formed as a growth associated type of
      secondary metabolite based on fermentation profile analysis.

PMID- 22621956
TI  - Influence of adenotonsillectomy on hard palate dimensions.
AB  - OBJECTIVE: To evaluate hard palate width and height in mouth-breathing children
      pre- and post-adenotonsillectomy. METHODS: We evaluated 44 children in the 3-6
      year age bracket, using dental study casts in order to determine palatal height,
      intercanine width, and intermolar width. The children were divided into two
      groups: nasal breathing (n=15) and mouth breathing (n=29). The children in the
      latter group underwent adenotonsillectomy. The study casts were obtained prior to
      adenotonsillectomy, designated time point 1 (T1), at 13 months after
      adenotonsillectomy (T2), and at 28 months after adenotonsillectomy (T3). Similar
      periods of observation were obtained for nasal breathing children. RESULTS: At
      T1, there was a significantly lower intercanine width in mouth breathing
      children; intermolar width and palate height were similar between groups. After
      surgery, there was a significant increase in all the analyzed parameters in both
      groups, probably due to facial growth. Instead, the increase in intercanine width
      was substantially more prominent in mouth breathing children than in nasal
      breathing children, and the former difference failed in significance after the
      procedure. CONCLUSIONS: There were no significant differences between the nasal
      breathing and mouth-breathing children in terms of intermolar width and palatal
      height prior to or after tonsillectomy. Although intercanine width was initially
      narrower in the mouth-breathing children, it showed normalization after the
      surgical procedure. These results confirm that the restoration of nasal breathing
      is central to proper occlusal development.

PMID- 22621957
TI  - Clinical, molecular, and cellular immunologic findings in patients with SP110
      associated veno-occlusive disease with immunodeficiency syndrome.
AB  - BACKGROUND: Mutations in the SP110 gene result in infantile onset of the
      autosomal recessive primary immunodeficiency disease veno-occlusive disease with
      immunodeficiency syndrome (VODI), which is characterized by
      hypogammaglobulinemia, T-cell dysfunction, and a high frequency of hepatic veno
      occlusive disease. OBJECTIVES: We sought to further characterize the clinical
      features, B-lineage cellular immunologic findings, and molecular pathogenesis of
      this disorder in 9 patients with new diagnoses, including 4 novel mutations from
      families of Italian, Hispanic, and Arabic ethnic origin. METHODS: Methods used
      include clinical review; Sanger DNA sequencing of the SP110 gene; determination
      of transfected mutant protein function by using immunofluorescent studies in Hep
      2 cells; quantitation of B-cell subsets by means of flow cytometry; assessments
      of B-cell function after stimulation with CD40 ligand, IL-21, or both; and
      differential gene expression array studies of EBV-transformed B cells. RESULTS:
      We confirm the major diagnostic criteria and the clinical utility of SP110
      mutation testing for the diagnosis of VODI. Analysis of 4 new alleles confirms
      that VODI is caused by reduced functional SP110 protein levels. Detailed B-cell
      immunophenotyping demonstrated that Sp110 deficiency compromises the ability of
      human B cells to respond to T cell-dependent stimuli and differentiate into
      immunoglobulin-secreting cells in vitro. Expression microarray studies have
      identified pathways involved in B-lymphocyte differentiation and macrophage
      function. CONCLUSION: These studies show that a range of mutations in SP110 that
      cause decreased SP110 protein levels and impaired late B-cell differentiation
      cause VODI and that the condition is not restricted to the Lebanese population.

PMID- 22621958
TI  - Cardioprotective effects of metformin and vildagliptin in adult rats with insulin
      resistance induced by a high-fat diet.
AB  - Insulin resistance has been shown to be associated with cardiac sympathovagal
      imbalance, myocardial dysfunction, and cardiac mitochondrial dysfunction. Whereas
      metformin is a widely used antidiabetic drug to improve insulin resistance,
      vildagliptin is a novel oral antidiabetic drug in a group of dipeptidyl peptidase
      4 inhibitors in which its cardiac effect is unclear. This study aimed to
      determine the cardiovascular effects of metformin and vildagliptin in rats with
      insulin resistance induced by high-fat diet. Male Wistar rats were fed with
      either a normal diet or high-fat diet (n =24 each) for 12 wk. Rats in each group
      were divided into three subgroups to receive the vehicle, metformin (30 mg/kg,
      twice daily), or vildagliptin (3 mg/kg, once daily) for another 21 d. Heart rate
      variability (HRV), cardiac function, and cardiac mitochondrial function were
      determined and compared among these treatment groups. Rats exposed to a high-fat
      diet developed increased body weight, visceral fat, plasma insulin, cholesterol,
      oxidative stress, depressed HRV, and cardiac mitochondrial dysfunction. Metformin
      and vildagliptin did not alter body weight and plasma glucose levels but
      decreased the plasma insulin, total cholesterol, and oxidative stress levels.
      Although both metformin and vildagliptin attenuated the depressed HRV, cardiac
      dysfunction, and cardiac mitochondrial dysfunction, vildagliptin was more
      effective in this prevention. Furthermore, only vildagliptin prevented cardiac
      mitochondrial membrane depolarization caused by consumption of a high-fat diet.
      We concluded that vildagliptin is more effective in preventing cardiac
      sympathovagal imbalance and cardiac dysfunction, as well as cardiac mitochondrial
      dysfunction, than metformin in rats with insulin resistance induced by high-fat
      diet.

PMID- 22621959
TI  - Impairments to the GH-IGF-I axis in hSOD1G93A mice give insight into possible
      mechanisms of GH dysregulation in patients with amyotrophic lateral sclerosis.
AB  - GH deficiency has been found in subjects with amyotrophic lateral sclerosis
      (ALS). Disrupted endocrine function could contribute to the progressive muscle
      loss and hypermetabolism seen in ALS. It is not possible to study all the
      elements of the GH-IGF-I axis in ALS patients. Consequently, it remains unclear
      whether dysfunctional GH secretion contributes to disease pathogenesis and why GH
      and IGF-I directed treatment strategies are ineffective in human ALS. The
      hSOD1(G93A) transgenic mouse model is useful for the detailed investigation of
      the pathogenesis of ALS. We report that symptomatic male hSOD1(G93A) transgenic
      mice exhibit a deficiency in GH secretion similar to that seen in human ALS.
      Further characterization of the GH-IGF-I axis in hSOD1(G93A) mice reveals central
      and peripheral abnormalities that are not found in wild-type age-matched
      controls. Specifically, we observe aberrant endogenous pulsatile GH secretion,
      reduced pituitary GH content, and decreased circulating levels of IGF-I,
      indicating global GH deficiency in hSOD1(G93A) mice. Furthermore, a reduction in
      the expression of the IGF-I receptor alpha-subunit in skeletal muscle and lumbar
      spinal cords of hSOD1(G93A) mice suggests impaired IGF-I signaling within these
      tissues. This is the first account of disrupted GH secretion in a transgenic
      mouse model of ALS. These observations are essential for the development of
      effective GH and IGF-I targeted therapies in ALS.

PMID- 22621960
TI  - Identification of permissive insertion sites for generating functional
      fluorescent mineralocorticoid receptors.
AB  - The mineralocorticoid receptor (MR), a member of the nuclear receptor superfamily
      of transcription factors, is activated by aldosterone and mediates its natriferic
      action in tight epithelia. MR is also expressed in nonepithelial tissues.
      Importantly, it mediates the deleterious effects of inappropriately high
      aldosterone levels in the heart, in which it induces the development of cardiac
      fibrosis. Antagonism of MR in humans is useful in the treatment of severe cardiac
      failure and some forms of hypertension. Despite the important pathophysiological
      and pharmacological role of this receptor, many important questions about its
      cellular biology and functional roles remain unanswered. A major challenge in the
      study of MR is the unavailability of fully functional fluorescent derivatives of
      the receptor. In this study we have created a library of MR mutants with
      insertions of the yellow fluorescent protein in various internal locations in the
      receptor using a random-insertion transposon-based technique. Screening of this
      library using a transactivation assay allowed us to identify several fluorescent
      constructs that retain functionality. Detailed characterization of one of these
      construct showed that it induces aldosterone-target genes such as the epithelial
      Na(+) channel subunits and the serum and glucocorticoid-induced kinase 1 at
      physiological concentrations of aldosterone to an equal extent than the wild-type
      receptor. Furthermore, aldosterone affinity, hormone-induced nuclear
      translocation, DNA binding and regulation of nongenomic pathways are all
      indistinguishable from the wild-type receptor. This new set of fluorescent MR
      derivatives provides a useful tool for studying the cell biology of the receptor.

PMID- 22621961
TI  - Embryonic birthdate of hypothalamic leptin-activated neurons in mice.
AB  - The hypothalamus plays a critical role in the regulation of energy balance.
      Neuroanatomical and mouse genetic data have defined a core circuitry in the
      hypothalamus that mediates many of the effects of leptin on feeding and energy
      balance regulation. The present study used 5-bromo-2'-deoxyuridine (a marker of
      dividing cells) and a neuronal marker to systematically examine neurogenesis in
      the mouse embryonic hypothalamus, particularly the birth of neurons that relay
      leptin signaling. The vast majority of neurons in hypothalamic nuclei known to
      control energy balance is generated between embryonic days (E) 12 and E16, with a
      sharp peak of neurogenesis occurring on E12. Neurons in the dorsomedial and
      paraventricular nuclei and the lateral hypothalamic area are born between E12 and
      E14. The arcuate and ventromedial nuclei exhibit a relatively longer neurogenic
      period. Many neurons in these nuclei are born on E12, but some neurons are
      generated as late as E16. We also examined the birth of leptin-activated cells by
      coupling the 5-bromo-2'-deoxyuridine staining with cFos immunohistochemistry.
      Remarkably, the majority of leptin-activated cells in the adult hypothalamus were
      also born during a discrete developmental window on E12. These results provide
      new insight into the development of hypothalamic neurons that control feeding and
      identify important developmental periods when alterations in the intrauterine
      environment may affect hypothalamic neurogenesis and produce long-term
      consequences on hypothalamic cell numbers.

PMID- 22621962
TI  - The Neospora caninum-Spain 7 isolate induces placental damage, fetal death and
      abortion in cattle when inoculated in early gestation.
AB  - The Nc-Spain 7 isolate of Neospora caninum, which was newly obtained from an
      asymptomatic congenitally infected calf, demonstrated a similar virulence as Nc-1
      strain in mouse models. The aim of this study was to characterize the
      pathogenesis of Nc-Spain 7 isolate in cattle after experimental infection at 65
      days of gestation. For this purpose, thirteen pregnant heifers were divided into
      three groups as follows: group A: 7 heifers inoculated with 1 * 10(8) tachyzoites
      of Nc-Spain 7 isolate; group B: 4 heifers inoculated with 1 * 10(8) tachyzoites
      of Nc 1 strain; and group C: 2 heifers received PBS. Serum samples were collected
      weekly and heparinized blood samples were collected three times (0, 28 and 42
      days after inoculation) by jugular venipuncture. Placenta and fetal tissue
      samples were collected at time of necropsy. Specific antibody response in the
      dams was tested by IFAT, indirect ELISA, and rNcGRA7 and rNcSAG4 based-ELISA.
      Specific antibody response in fetal fluids was tested by IFAT. IFN-gamma
      production was measured after in vitro culture of PBMC and the supernatant was
      assessed using a commercial kit (BOVIGAM). A significant increase in N. caninum
      antibody responses was detected in groups A and B by IFAT and by i-ELISA from day
      14 after inoculation onwards. Besides, antibody response against rNCGra7 protein
      was also detected in all inoculated heifers by rNcGra7-based ELISA. Four fetuses
      from group A and one from group B were aborted between 3 and 5 weeks after
      infection. In the recovered fetuses, only 3 out of 4 fetal fluids from fetuses of
      group A and 1 out of 3 of group B were seropositive by IFAT, but all of them were
      positive by PCR. Transplacental transmission could be determined in all fetuses
      from groups A and B by PCR and/or IHC. Heifers of group C and their fetuses
      remained negative by all techniques. The results of this study demonstrate that
      the NC-Spain 7 isolate could be transmitted transplacentally, and produced fetal
      death and abortion in cattle.

PMID- 22621963
TI  - Prospective evaluation of fluorescence-in situ-hybridization to detect bladder
      cancer: results from the UroScreen-Study.
AB  - BACKGROUND: UroScreen is a prospective study for early diagnosis of bladder
      cancer (BC) in chemical workers formerly exposed to aromatic amines, aimed to
      assess the performance of molecular tumor markers in comparison with urinary
      cytology. Here we evaluate the cancer-predictive values and potential effect
      modifiers of fluorescence-in-situ-hybridization (FISH). SUBJECTS AND METHODS: A
      FISH test was performed in 7,091 urine samples from 1,609 subjects between 2007
      and 2010. Cystoscopy was recommended in case of positive or suspicious findings.
      Logistic regression models were applied to estimate the influence of potential
      test confounders like urinary creatinine and hematuria on detecting BC. Receiver
      operating characteristic (ROC) curves for FISH were adjusted for test
      confounders. Cancer-predictive values were calculated from test results in the
      last sample before diagnosis. RESULTS: Histopathology revealed 16 incidental BCs
      and 5 recurrent tumors in 20 study participants. FISH was positive in 9 BC cases
      of which 7 were high grade. Cytology detected 8 tumors. FISH overlapped with
      cytology in 7 cases. Sensitivity was 45.0% and PPV (positive predictive value)
      was 16.4% in all and 53.85% and 13.21% in high-grade tumors. Specificity and
      negative predictive value (NPV) were 96.97% and 99.26% in all bladder tumors. BC
      detected during UroScreen was associated with an odds ratio (OR) of 6.88 (95% CI
      1.72-27.44) for positive FISH and with an OR of 8.81 (95% CI 1.41-54.96) for
      gross hematuria. The adjusted area under the curve was 0.77 (95% CI 0.62-0.92)
      for all and for high-grade lesions (0.85; 95% CI 0.69-1.00). CONCLUSIONS: FISH
      showed a performance in detecting bladder cancer comparable to cytology but a
      larger number or false-positive results. It remains to be investigated if
      chromosomal instability can be detected earlier than morphologic changes of
      exfoliated bladder cancer cells.

PMID- 22621964
TI  - Comment on: Patients' experience and outcomes after laparoscopic adjustable
      gastric banding in Washington state.

PMID- 22621965
TI  - Transcriptional regulation of temperature-induced remodeling of muscle
      bioenergetics in goldfish.
AB  - Central to mammalian mitochondrial biogenesis is the transcriptional master
      regulator peroxisome proliferator-activated receptor (PPAR)-gamma coactivator
      1alpha (PGC-1alpha), and a network of DNA-binding proteins it coactivates. We
      explored the role of this pathway in muscle mitochondrial biogenesis in response
      to thermal acclimation in goldfish (Carassius auratus). We investigated the
      transcriptional response of PGC-1alpha, PGC-1beta, and their antagonist the
      nuclear receptor interacting protein 1 (RIP140), as well as the mRNA and protein
      patterns of DNA-binding proteins that bind PGC-1, including nuclear respiratory
      factors (NRF) 1 and 2, retinoid X receptor alpha (RXRalpha), estrogen-related
      receptor alpha (ERRalpha), thyroid receptor alpha-1 (TRalpha-1), PPARalpha, and
      PPARbeta/delta, and the host cell factor 1 (HCF1), which links PGC-1 and NRF-2.
      Cold-acclimated (4 degrees C) fish had higher COX activities (4.5-fold) and COX4
      1 mRNA levels (3.5-fold per total RNA; 6.5-fold per gram tissue) than warm
      acclimated (32 degrees C) fish. The transcription factor patterns were profoundly
      influenced by changes in RNA per gram tissue (2-fold higher in cold fish) and
      nuclear protein content (2-fold higher in warm fish). In cold-acclimated fish,
      mRNA per gram tissue was elevated for PGC-1beta, RIP140, NRF-1, HCF1, NRF-2alpha,
      NRF-2beta-2, ERRalpha, PPAR beta/delta, and RXRalpha, but other transcriptional
      regulators either did not change (PGC-1alpha, PPARalpha) or even decreased
      (TRalpha-1). Nuclear protein levels in cold-acclimated fish were higher only for
      NRF-1; other proteins were either unaffected (NRF-2alpha, ERRalpha) or decreased
      (NRF-2beta1/2, TRalpha, RXRalpha). Collectively, these data support the role for
      NRF-1 in regulating cold-induced mitochondrial biogenesis in goldfish, with
      effects mediated by PGC-1beta, rather than PGC-1alpha.

PMID- 22621966
TI  - DeltaFosB in the supraoptic nucleus contributes to hyponatremia in rats with
      cirrhosis.
AB  - Bile duct ligation (BDL), a model of hepatic cirrhosis, is associated with
      dilutional hyponatremia and inappropriate vasopressin release. DeltaFosB staining
      was significantly increased in vasopressin and oxytocin magnocellular
      neurosecretory cells in the supraoptic nucleus (SON) of BDL rats. We tested the
      role of SON DeltaFosB in fluid retention following BDL by injecting the SON (n =
      10) with 400 nl of an adeno-associated virus (AAV) vector expressing DeltaJunD (a
      dominant negative construct for DeltaFosB) plus green fluorescent protein (GFP)
      (AAV-GFP-DeltaJunD). Controls were either noninjected or injected with an AAV
      vector expressing only GFP. Three weeks after BDL or sham ligation surgery, rats
      were individually housed in metabolism cages for 1 wk. Average daily water intake
      was significantly elevated in all BDL rats compared with sham ligated controls.
      Average daily urine output was significantly greater in AAV-GFP-DeltaJunD-treated
      BDL rats compared with all other groups. Daily average urine sodium concentration
      was significantly lower in AAV-GFP-DeltaJunD-treated BDL rats than the other
      groups, although average daily sodium excretion was not different among the
      groups. SON expression of DeltaJunD produced a diuresis in BDL rats that may be
      related to decreased circulating levels of vasopressin or oxytocin. These
      findings support the view that DeltaFosB expression in SON magnocellular
      secretory cells contribute to dilutional hyponatremia in BDL rats.

PMID- 22621967
TI  - Treatment with the vascular disrupting agent combretastatin is associated with
      impaired AQP2 trafficking and increased urine output.
AB  - Combretastatin A-4 disodium phosphate (CA4P) is a vascular disrupting agent known
      to mediate its effects primarily on tumor blood vessels. CA4P has previously been
      shown to induce a significant increase in mean arterial blood pressure and in
      hemoglobin concentration in mice. In the present study, we examined whether this
      is associated with a general leakage of water into certain tissues or with
      changes in renal water handling. Munich-Wistar rats received either CA4P (30
      mg/kg body wt) or saline intraperitoneally as a bolus injection. One hour later,
      hemoglobin concentration and mean blood pressure increased significantly. MRI
      showed no significant changes in tissue water content following CA4P
      administration. However, urine output and salt excretion increased 1 h after CA4P
      treatment, without changes in urinary and medullary osmolality. Aquaporin 2
      (AQP2) mRNA levels in kidney inner medulla did not change 1 h after CA4P
      treatment, but semiquantitative confocal laser-scanning microscopy analysis
      demonstrated a decrease in phosphorylated AQP2 (pS256-AQP2) apical distribution
      within the collecting ducts of CA4P-treated rats compared with the characteristic
      apical localization in control rats. Furthermore, we demonstrated that CA4P cause
      disruption of microtubules and a weaker apical labeling of pS256-AQP2 in
      collecting duct principal cells within 1 h. In conclusion, our data indicate that
      water escapes from the vascular system after CA4P treatment, and it may take
      place primarily through a renal mechanism. The CA4P-mediated increase in urine
      output seems to be a local effect in the collecting ducts due to reduced AQP2
      trafficking to the apical plasma membrane.

PMID- 22621968
TI  - Orosensory detection of sucrose, maltose, and glucose is severely impaired in
      mice lacking T1R2 or T1R3, but Polycose sensitivity remains relatively normal.
AB  - Evidence in the literature supports the hypothesis that the T1R2+3 heterodimer
      binds to compounds that humans describe as sweet. Here, we assessed the necessity
      of the T1R2 and T1R3 subunits in the maintenance of normal taste sensitivity to
      carbohydrate stimuli. We trained and tested water-restricted T1R2 knockout (KO),
      T1R3 KO and their wild-type (WT) same-sex littermate controls in a two-response
      operant procedure to sample a fluid and differentially respond on the basis of
      whether the stimulus was water or a tastant. Correct responses were reinforced
      with water and incorrect responses were punished with a time-out. Testing was
      conducted with a modified descending method of limits procedure across daily 25
      min sessions. Both KO groups displayed severely impaired performance and markedly
      decreased sensitivity when required to discriminate water from sucrose, glucose,
      or maltose. In contrast, when Polycose was tested, KO mice had normal EC(50)
      values for their psychometric functions, with some slight, but significant,
      impairment in performance. Sensitivity to NaCl did not differ between these mice
      and their WT controls. Our findings support the view that the T1R2+3 heterodimer
      is the principal receptor that mediates taste detection of natural sweeteners,
      but not of all carbohydrate stimuli. The combined presence of T1R2 and T1R3
      appears unnecessary for the maintenance of relatively normal sensitivity to
      Polycose, at least in this task. Some detectability of sugars at high
      concentrations might be mediated by the putative polysaccharide taste receptor,
      the remaining T1R subunit forming either a homodimer or heteromer with another
      protein(s), or nontaste orosensory cues.

PMID- 22621969
TI  - Roles of three branchial Na(+)-K(+)-ATPase alpha-subunit isoforms in freshwater
      adaptation, seawater acclimation, and active ammonia excretion in Anabas
      testudineus.
AB  - Three Na(+)-K(+)-ATPase (nka) alpha-subunit isoforms, nka alpha1a, nka alpha1b,
      and nka alpha1c, were identified from gills of the freshwater climbing perch
      Anabas testudineus. The cDNA sequences of nka alpha1a and nka alpha1b consisted
      of 3,069 bp, coding for 1,023 amino acids, whereas nka alpha1c was shorter by 22
      nucleotides at the 5' end. In freshwater, the quantity of nka alpha1c mRNA
      transcripts present in the gills was the highest followed by nka alpha1a and nka
      alpha1b that was almost undetectable. The mRNA expression of nka alpha1a was
      downregulated in the gills of fish acclimated to seawater, indicating that it
      could be involved in branchial Na(+) absorption in a hypoosmotic environment. By
      contrast, seawater acclimation led to an upregulation of the mRNA expression of
      nka alpha1b and to a lesser extent nka alpha1c, indicating that they could be
      essential for ion secretion in a hyperosmotic environment. More importantly,
      ammonia exposure led to a significant upregulation of the mRNA expression of nka
      alpha1c, which might be involved in active ammonia excretion. Both seawater
      acclimation and ammonia exposure led to significant increases in the protein
      abundance and changes in the kinetic properties of branchial Na(+)-K(+)-ATPase
      (Nka), but they involved two different types of Nka-immunoreactive cells. Since
      there was a decrease in the effectiveness of NH(4)(+) to substitute for K(+) to
      activate branchial Nka from fish exposed to ammonia, Nka probably functioned to
      remove excess Na(+) and to transport K(+) instead of NH(4)(+) into the cell to
      maintain intracellular Na(+) and K(+) homeostasis during active ammonia
      excretion.

PMID- 22621971
TI  - High viral load is associated with poor overall and recurrence-free survival of
      hepatitis B virus-related hepatocellular carcinoma after curative resection: a
      prospective cohort study.
AB  - PURPOSE: The aim of this prospective cohort study was to investigate the impact
      of preoperative hepatitis B viral load, as well as postoperative antiviral
      therapy, on the risk of long-term survival after curative resection of hepatitis
      B virus-related hepatocellular carcinoma (HCC). METHODS: A prospective cohort of
      hepatitis B virus-related HCC patients undergoing curative resection from 2002 to
      2008 was studied. According to preoperative viral load (using 10,000 copies/mL of
      hepatitis B virus DNA level as cut-off value), two groups were compared.
      Prognostic factors for overall survival and recurrence-free survival were
      evaluated. Additionally, subgroup analysis was conducted in patients with high
      viral load to investigate prediction of postoperative antiviral therapy on the
      long-term prognosis. RESULTS: With a median follow-up of 49.1 months, patients
      with high viral load had lower median overall survival (78.3 months vs. 111.4
      months, P<0.001) and RFS (44.6 months vs. 94.8 months, P<0.001) compared with
      those with low viral load. Multivariate analysis revealed that preoperative high
      viral load was an independent risk factor affecting both overall survival and
      recurrence-free survival (both P<0.001). The subgroup analysis revealed that
      postoperative antiviral therapy independently improved recurrence-free survival
      for patients with high viral load (P=0.001). CONCLUSIONS: Hepatitis B virus
      related HCC patients with preoperative high viral load led to poorer overall and
      recurrence-free survival than those with low viral load after curative resection.
      To prevent postoperative recurrence, antiviral therapy should be initiated in
      those patients with hepatitis B virus DNA >= 10,000 copies/ml.

PMID- 22621972
TI  - Curve aligning approach for gait authentication based on a wearable
      accelerometer.
AB  - Gait authentication based on a wearable accelerometer is a novel biometric which
      can be used for identity identification, medical rehabilitation and early
      detection of neurological disorders. The method for matching gait patterns tells
      heavily on authentication performances. In this paper, curve aligning is
      introduced as a new method for matching gait patterns and it is compared with
      correlation and dynamic time warping (DTW). A support vector machine (SVM) is
      proposed to fuse pattern-matching methods in a decision level. Accelerations
      collected from ankles of 22 walking subjects are processed for authentications in
      our experiments. The fusion of curve aligning with backward-forward accelerations
      and DTW with vertical accelerations promotes authentication performances
      substantially and consistently. This fusion algorithm is tested repeatedly. Its
      mean and standard deviation of equal error rates are 0.794% and 0.696%,
      respectively, whereas among all presented non-fusion algorithms, the best one
      shows an EER of 3.03%.

PMID- 22621970
TI  - Associations of plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D
      concentrations with death and progression to maintenance dialysis in patients
      with advanced kidney disease.
AB  - BACKGROUND: Low vitamin D concentrations are prevalent in patients with chronic
      kidney disease (CKD). We investigated the relationship between plasma 25
      hydroxyvitamin D (25[OH]D) or 1,25-dihydroxyvitamin D (1,25[OH](2)D)
      concentrations with death, cardiovascular events, and dialysis therapy initiation
      in patients with advanced CKD. STUDY DESIGN: The HOST (Homocysteinemia in Kidney
      and End Stage Renal Disease) Study was a randomized double-blind trial evaluating
      the effects of high doses of folic acid on death and long-term dialysis therapy
      initiation in patients with advanced CKD (stages 4 and 5 not yet on dialysis
      therapy). 25(OH)D and 1,25(OH)(2)D were measured in stored plasma samples
      obtained 3 months after trial initiation and evaluated at clinically defined
      cutoffs (<10, 10-30, and >30 ng/mL) and tertiles (<15, 15-22, and >22 pg/mL),
      respectively. Cox proportional hazard models were used to examine the association
      between vitamin D concentrations and clinical outcomes. SETTING & PARTICIPANTS:
      1,099 patients with advanced CKD from 36 Veteran Affairs Medical Centers.
      PREDICTORS: 25(OH)D and 1,25(OH)(2)D concentrations. OUTCOMES: Death,
      cardiovascular events, and time to initiation of long-term dialysis therapy.
      RESULTS: After a median follow-up of 2.9 years, 41% (n = 453) died, whereas 56%
      (n = 615) initiated dialysis therapy. Mean 25(OH)D and 1,25(OH)(2)D
      concentrations were 21 +/- 10 ng/mL and 20 +/- 11 pg/mL, respectively. After
      adjustment for potential confounders, the lowest tertile of 1,25(OH)(2)D was
      associated with death (HR, 1.33; 95% CI, 1.01-1.74) and initiation of long-term
      dialysis therapy (HR, 1.78; 95% CI, 1.40-2.26) compared with the highest tertile.
      The association with death and initiation of dialysis therapy was moderately
      attenuated after adjustment for plasma fibroblast growth factor 23 (FGF-23)
      concentrations (HRs of lower tertiles of 1.20 [95% CI, 0.91-1.58] and 1.56 [95%
      CI, 1.23-1.99], respectively, compared with highest tertile). There was no
      association between 25(OH)D concentrations and outcomes. LIMITATIONS:
      Participants were mostly men. CONCLUSIONS: Low plasma 1,25(OH)(2)D concentrations
      are associated with death and initiation of long-term dialysis therapy in
      patients with advanced CKD. FGF-23 level may attentuate this relationship.

PMID- 22621974
TI  - Fine tuning of cell signals by glycosylation.
AB  - Carbohydrates on the glycoproteins and glycosphingolipids expressed on the cell
      surface membrane play crucial roles in the determination of cell fates by being
      involved in the fine tuning of cell signalling as reaction molecules in the front
      line to various extrinsic stimulants. In glycoproteins, modification of proteins
      is performed by substitution of sugar chains to one or multiple sites of
      individual proteins, leading to quantitative and qualitative changes of receptor
      functions in the cell membrane. As for glycosphingolipids, majority of them
      consist of two moieties, i.e. carbohydrates and ceramides, and are localized in
      the microdomains such as lipid rafts or detergent-resistant microdomains. They
      generate and/or modulate cell signals to determine the cell fates by interacting
      with various carbohydrate-recognizing proteins. Modes of glycosylation and
      mechanisms by which glycosylation is involved in the regulation of cell signals
      are now hot subjects in glycobiology.

PMID- 22621975
TI  - Adenovirus receptors: implications for targeting of viral vectors.
AB  - Cancer, cardiovascular disease, and infectious diseases are all global health
      threats. To combat these diseases with gene therapies, adenovirus-based vectors
      have been developed. Although certain clinical trials appear successful, there is
      an obvious need to improve the efficacy of most adenovirus-based vectors. For the
      most commonly used vector (based on type 5; Ad5), a main problem is its
      accumulation in the liver, which can be attributed to interactions with specific
      host factors. The diverse tropism for types other than Ad5 implies that vectors
      based on alternative types could have advantages. The numerous interactions of
      different adenoviruses with host molecules - such as the recently identified
      desmoglein-2 receptor - may cause novel and unexpected obstacles, but also may
      provide possibilities for vectors based on alternative types. This review
      provides an update of new and previously known molecules that mediate cellular
      attachment of human adenoviruses and discusses how these may influence the
      targeting of adenovirus-based vectors.

PMID- 22621973
TI  - Effects of HIV and early life stress on amygdala morphometry and neurocognitive
      function.
AB  - Both HIV infection and high levels of early life stress (ELS) have been related
      to abnormalities in frontal-subcortical structures, yet the combined effects of
      HIV and ELS on brain structure and function have not been previously
      investigated. In this study we assessed 49 non-demented HIV-seropositive (HIV+)
      and 47 age-matched HIV-seronegative healthy control (HC) adults. Levels of ELS
      exposure were quantified and used to define four HIV-ELS groups: HC Low-ELS (N =
      20); HC High-ELS (N = 27); HIV+ Low-ELS (N = 24); HIV+ High-ELS (N = 25). An
      automated segmentation tool measured volumes of brain structures known to show
      HIV-related or ELS-related effects; a brief neurocognitive battery was
      administered. A significant HIV-ELS interaction was observed for amygdala
      volumes, which was driven by enlargements in HIV+ High-ELS participants. The HIV+
      High-ELS group also demonstrated significant reductions in psychomotor/processing
      speed compared with HC Low-ELS. Regression analyses in the HIV+ group revealed
      that amygdala enlargements were associated with higher ELS, lower nadir CD4
      counts, and reduced psychomotor/processing speed. Our results suggest that HIV
      infection and high ELS interact to increase amygdala volume, which is associated
      with neurocognitive dysfunction in HIV+ patients. These findings highlight the
      lasting neuropathological influence of ELS and suggest that high ELS may be a
      significant risk factor for neurocognitive impairment in HIV-infected
      individuals.

PMID- 22621976
TI  - Depositional fluxes and residence time of atmospheric radioiodine (131I) from the
      Fukushima accident.
AB  - Activities of radioiodine ((131)I) along with (210)Pb and (210)Po in time series
      precipitation samples were measured to determine the depositional fluxes of
      (131)I in the Southern United States and its removal rate and residence time in
      the atmosphere during the Fukushima nuclear accident. Radioiodine released from
      the Fukushima accident reached the Southern United States within 11 days, giving
      rise to a concurrent (131)I peak and anomalous (210)Po/(210)Pb ratios in the
      precipitation samples. The cumulative (131)I depositional flux was 4.6 +/- 0.2 Bq
      m(-2) during the maximum fallout. The removal rate of (131)I out of the
      atmosphere, derived from a definite (131)I integral model, ranged from 0.03 to
      0.14 d(-1) with an average of 0.08 +/- 0.02 d(-1), which corresponds to a
      residence time of (131)I in the atmosphere of 12 +/- 3 days, consistent with the
      resident timescale constrained by the (210)Po/(210)Pb disequilibrium technique.
      These results support our hypothesis that radioiodine was removed from the
      atmosphere by precipitation within two weeks. It seemed that regions reachable by
      (131)I transport within two weeks from Fukushima Japan would receive much more
      fallout, whereas places outside that distance would be relatively less polluted
      with radionuclides.

PMID- 22621977
TI  - Heteronuclear Adiabatic Relaxation Dispersion (HARD) for quantitative analysis of
      conformational dynamics in proteins.
AB  - NMR relaxation methods probe biomolecular motions over a wide range of
      timescales. In particular, the rotating frame spin-lock R(1rho) and Carr-Purcell
      Meiboom-Gill (CPMG) R(2) experiments are commonly used to characterize MUs to ms
      dynamics, which play a critical role in enzyme folding and catalysis. In an
      effort to complement these approaches, we introduced the Heteronuclear Adiabatic
      Relaxation Dispersion (HARD) method, where dispersion in rotating frame
      relaxation rate constants (longitudinal R(1rho) and transverse R(2rho)) is
      created by modulating the shape and duration of adiabatic full passage (AFP)
      pulses. Previously, we showed the ability of the HARD method to detect chemical
      exchange dynamics in the fast exchange regime (k(ex)~10(4)-10(5) s(-1)). In this
      article, we show the sensitivity of the HARD method to slower exchange processes
      by measuring R(1rho) and R(2rho) relaxation rates for two soluble proteins
      (ubiquitin and 10C RNA ligase). One advantage of the HARD method is its nominal
      dependence on the applied radio frequency field, which can be leveraged to
      modulate the dispersion in the relaxation rate constants. In addition, we also
      include product operator simulations to define the dynamic range of adiabatic
      R(1rho) and R(2rho) that is valid under all exchange regimes. We conclude from
      both experimental observations and simulations that this method is complementary
      to CPMG-based and rotating frame spin-lock R(1rho) experiments to probe
      conformational exchange dynamics for biomolecules. Finally, this approach is
      germane to several NMR-active nuclei, where relaxation rates are frequency-offset
      independent.

PMID- 22621978
TI  - Treatment of post-implantation aneurysm growth by laparoscopic sac fenestration:
      long-term results.
AB  - OBJECTIVES: Sac growth after endovascular aneurysm repair (EVAR) is an important
      finding, which may influence prognosis. In case of a type II endoleak or
      endotension, clipping of side branches and subsequent sac fenestration has been
      presented as a therapeutic alternative. The long-term clinical efficacy of this
      procedure is unknown. METHODS: The study included eight patients who underwent
      laparoscopic aortic collateral clipping and sac fenestration for enlarging
      aneurysms following EVAR. Secondary interventions and clinical outcome were
      retrieved from hospital records. Sac behaviour was evaluated measuring volumes on
      periodical computed tomography angiography (CTA) imaging using dedicated
      software. RESULTS: Follow-up had a median length of 6.6 (range 0.6-8.6) years.
      During this time, only three patients successfully achieved durable aneurysm
      shrinkage (n = 2) or stability (n = 1). The remaining patients suffered
      persistent (n = 2) or recurrent sac growth (n = 3), all regarded as failure of
      fenestration. A total of six additional interventions were performed, comprising
      open conversion (n = 2), relining (n = 1) and implantation of iliac extensions (n
      = 3). All additional interventions were successful at arresting further sac
      growth during the remainder of follow-up. CONCLUSIONS: Despite being a less
      invasive alternative to conversion and open repair, the long-term outcome of sac
      fenestration is unpredictable and additional major procedures were often
      necessary to arrest sac growth.

PMID- 22621979
TI  - Endovenous simulated laser experiments at 940 nm and 1470 nm suggest wavelength
      independent temperature profiles.
AB  - BACKGROUND: EVLA has proven to be very successful, but the optimum methods for
      energy delivery have still not been clarified. A better understanding of the
      mechanism of action may contribute to achieving a consensus on the best laser
      method and the most effective use of laser parameters, resulting in optimal
      clinical outcomes, maintaining high success rates with minimal adverse events.
      The aim of this study is to assess the impact of wavelength, pullback speed and
      power level on the endovenous temperature profile in an experimental setting.
      METHODS: In an experimental setting, temperature measurements were performed
      using thermocouples. The experimental set-up consisted of a transparent box in
      which a glass tube was fixed. Different laser parameters (wavelength and power)
      and 2 different pullback speeds (2 and 5 mm/s) were used. Thermocouples were
      placed at different distances from the fiber tip. Validity of the experimental
      setting was assessed by performing the same temperature measurements using a
      stripped varicose vein. The maximal temperature rise and the time span that the
      temperature was above collagen denaturation temperature were measured. RESULTS:
      The experiments showed that decreasing the pullback speed (2 mm/s) and increasing
      the power (up to 14 W) both cause higher maximal temperature and a longer time
      above the temperature for collagen denaturation. The use of different laser
      wavelengths (940 or 1470 nm) did not influence the temperature profile.
      CONCLUSION: The results of our experiments show that wavelength on its own has
      not been demonstrated to be an important parameter to influence the temperature
      profile.

PMID- 22621980
TI  - Biofuel cell as a power source for electronic contact lenses.
AB  - Here we present unequivocal experimental proof that microscale cofactor- and
      membrane-less, direct electron transfer based enzymatic fuel cells do produce
      significant amounts of electrical energy in human lachrymal liquid (tears). 100
      MUm diameter gold wires, covered with 17 nm gold nanoparticles, were used to
      fashion three-dimensional nanostructured microelectrodes, which were biomodified
      with Corynascus thermophilus cellobiose dehydrogenase and Myrothecium verrucaria
      bilirubin oxidase as anodic and cathodic bioelements, respectively. The following
      characteristics of miniature glucose/oxygen biodevices operating in human tears
      were registered: 0.57 V open-circuit voltage, about 1 MUW cm(-2) maximum power
      density at a cell voltage of 0.5 V, and more than 20 h operational half-life.
      Theoretical calculations regarding the maximum recoverable electrical energy can
      be extracted from the biofuel and the biooxidant, glucose and molecular oxygen,
      each readily available in human lachrymal liquid, fully support our belief that
      biofuel cells can be used as electrical power sources for so called smart contact
      lenses.

PMID- 22621981
TI  - Bi-enzyme synergetic catalysis to in situ generate coreactant of peroxydisulfate
      solution for ultrasensitive electrochemiluminescence immunoassay.
AB  - A novel electrochemiluminescence (ECL) immunosensor for ultrasensitive detection
      of alpha-1-fetoprotein (AFP) was designed based on the in situ bi-enzymatic
      reaction to generate coreactant of peroxydisulfate for signal amplification. In
      this work, AuNPs were electrodeposited on the glassy carbon electrode (GCE)
      surface, which promoted the electron transfer. Then, L-cysteine and another layer
      of AuNPs were, respectively assembled onto the modified electrode surface, which
      formed the multilayer films for amplifying the ECL signal of peroxydisulfate and
      immobilizing antibody. At last, glucose oxidase (GOD) and horseradish peroxidase
      (HRP) were employed to block the nonspecific binding sites. When proper amounts
      of glucose were added in the detection solution, GOD catalyzed the oxidation of
      glucose to generate H(2)O(2), which could be further catalyzed by HRP to generate
      O(2) for the signal amplification. The linear range for AFP detection was 0.001
      100 ng mL(-1), with a low detection limit of 3.3 * 10(-4) ng mL(-1). The novel
      strategy has the advantages of simplicity, sensitivity, good selectivity and
      reproducibility which might hold a new promise for highly sensitive bioassays
      applied in clinical detection.

PMID- 22621982
TI  - Multifunctional Fe3O4 core/Ni-Al layered double hydroxides shell nanospheres as
      labels for ultrasensitive electrochemical immunoassay of subgroup J of avian
      leukosis virus.
AB  - A novel electrochemical immunosensor for ultrasensitive detection of subgroup J
      of avian leukosis virus (ALVs-J) was designed by using graphene sheets (GS)
      layered double hydroxides (LDHs) composites modified electrode with
      multifunctional Fe(3)O(4) core/Ni-Al LDHs shell (LDHs@Fe(3)O(4)) nanospheres as
      labels. At first, the GS-LDHs were used for the immunosensor platform for
      improving the electronic transmission rate as well as increasing the surface area
      to capture a large amount of primary antibodies (Ab(1)). After that, ferrocene
      (Fc), secondary antibodies (Ab(2)) and horseradish peroxidase (HRP)
      multifunctional LDHs@Fe(3)O(4) nanospheres were used as labels with high load
      amount and good biological activity. Subsequently, in presence of H(2)O(2),
      amplified signals were obtained by an electrochemical sandwich immunoassay
      protocol. To embody the signal amplification property of the protocol, the
      analytical properties of various immunosensor platform and labels were compared
      in detail. Under optimal conditions, the reduction peak currents of the
      electrochemical immunosensor were proportional to the ALVs-J concentration over
      the range from 10(2.32) to 10(5.50) TCID(50)/mL with a low detection limit (180
      TCID(50)/mL, S/N=3). The resulting immunosensor also displayed a good
      selectivity, reproducibility and stability.

PMID- 22621983
TI  - Predicting sleep quality from stress and prior sleep--a study of day-to-day
      covariation across six weeks.
AB  - BACKGROUND/OBJECTIVES: The connection between stress and sleep is well
      established in cross-sectional questionnaire studies and in a few prospective
      studies. Here, the intention was to study the link between stress and sleep on a
      day-to-day basis across 42 days. METHODS: Fifty participants kept a sleep/wake
      diary across 42 days and responded to daily questions on sleep and stress. The
      results were analyzed with a mixed model approach using stress during the prior
      day to predict morning ratings of sleep quality. RESULTS: The results showed that
      bedtime stress and worries were the main predictors of sleep quality, but that,
      also, late awakening, short prior sleep, high quality of prior sleep, and good
      health the prior day predicted higher sleep quality. CONCLUSIONS: Stress during
      the day predicts subsequent sleep quality on a day-to-day basis across 42 days.
      The observed range of variation in stress/worries was modest, which is why it is
      suggested that the present data underestimates the impact of stress on subsequent
      sleep quality.

PMID- 22621985
TI  - Intractable and rare diseases research in Asia.
AB  - Intractable and rare diseases are an important public health issue and a
      challenge to medical care. In recent years, much progress has been made in the
      United States (US), the European Union (EU), and some parts of Asia including
      Japan, South Korea, and Taiwan, involving specific legislation to encourage
      discovery and development of orphan drugs, patients' advocacy organizations to
      provide vast information on intractable and rare diseases and improve patients'
      access to healthcare, special research programs to strengthen basic and applied
      research on intractable and rare diseases, and so on. While China is also
      actively promoting regulation of intractable and rare diseases, but still lags
      far behind the US, EU, Japan, and other countries and regions with orphan drug
      legislation. Based on systematic analysis of the current status and future
      perspectives for intractable and rare diseases in Asia, we recommend that three
      important aspects of support from government, patients' advocacy organizations
      and rare disease registry networks, special research programs and global
      information exchange platform, should be given great attention in promoting the
      development of intractable and rare diseases research in Asian countries.

PMID- 22621984
TI  - Apolipoprotein E genotype is associated with CT angiography spot sign in lobar
      intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: The CT angiography (CTA) spot sign predicts hematoma
      expansion and poor outcome in patients with primary intracerebral hemorrhage
      (ICH). The biological underpinnings of the spot sign remain poorly understood; it
      may be that the underlying vasculopathy influences its presence. Therefore, we
      conducted a study to identify genetic predictors of the spot sign. METHODS: In an
      ongoing prospective cohort study, we analyzed 371 patients with CTA and genetic
      data available. CTAs were reviewed for the spot sign by 2 experienced readers,
      blinded to clinical data, according to validated criteria. Analyses were
      stratified by ICH location. RESULTS: In multivariate analysis, patients on
      warfarin were more likely to have a spot sign regardless of ICH location (OR,
      3.85; 95% CI, 1.33-11.13 in deep ICH and OR, 2.86; 95% CI, 1.33-6.13 in lobar
      ICH). Apolipoprotein E epsilon2, but not epsilon4, was associated with the
      presence of a spot sign in lobar ICH (OR, 2.09; 95% CI, 1.05-4.19). There was no
      effect for epsilon2 or epsilon4 in deep ICH. CONCLUSIONS: Patients with ICH on
      warfarin are more likely to present with a spot sign regardless of ICH location.
      Among patients with lobar ICH, those who possess the apolipoprotein E epsilon2
      allele are more likely to have a spot sign. Given the established relationship
      between apolipoprotein E epsilon2 and vasculopathic changes in cerebral amyloid
      angiopathy, our findings suggest that both hemostatic factors and vessel
      pathology influence spot sign presence.

PMID- 22621986
TI  - Influence of hapten density on immunogenicity for anti-ciprofloxacin antibody
      production in mice.
AB  - To generate antibodies against small molecules, it is necessary to couple them as
      haptens to large carriers such as proteins. However, the immunogenicity of the
      conjugates usually has no linear correlation with the hapten-protein ratio, which
      may lead to large variations in the character of the desired antibodies. In the
      present study, ciprofloxacin (CPFX) was coupled to bovine serum albumin (BSA) in
      five different proportions using a modified carbodiimide method. The conjugates
      were characterized qualitatively by spectrophotometric absorption and
      electrophoresis methods. Mass spectrometry and the trinitrobenzene sulfonic acid
      method were adopted to assay the density of conjugates quantitatively. As a
      result, CPFX-BSA conjugates with various hapten densities (21-30 molecules per
      carrier protein) were obtained. After immunization in mice, ELISA tests showed
      that the antisera titer increased gradually with the increase of hapten density.
      The antibody obtained from the mice showed high sensitivity toward CPFX. These
      results revealed the relationship between hapten density and immunogenicity as
      well as an optimized conjugation approach for immunization purposes.

PMID- 22621987
TI  - Study pattern of snoring and associated risk factors among medical students.
AB  - Snoring can impair lifestyle and cause late cardiopulmonary complications. Early
      detection of snoring and timely intervention during adolescence can avoid
      complications. A single center prospective cross-sectional study was conducted in
      548 undergraduate 17-25 years old undergraduate medical students of CSM Medical
      University, Lucknow, who were interviewed on the basis of the modified Berlin
      Questionnaire along with their room-partners describing their snoring habits.
      Ninety-seven (17.7%) subjects were found to be snorers. Risk factors viz. day
      time sleepiness (European Stroke Scale (ESS) scores), smoking habits, alcohol
      intake, neck size and BMI were observed. The proportion of males, smokers, BMI,
      neck size and ESS scores were significantly (p < 0.001) higher in snorers than
      non snorers. Logistic regression found sex (OR = 5.73, 95% CI = 2.11-15.61),
      smoking (OR = 2.20, 95% CI = 0.97-5.62), BMI (OR = 3.16, 95% CI = 1.09-7.36) and
      neck size (OR = 2.03, 95% CI = 0.79-6.35) as significant (p < 0.01) independent
      risk factors for snoring. A clinically significant form of Sleep Disordered
      Breathing (Habitual snoring, ESS score >= 11 and BMI >= 25 kg/m2) was suspected
      in 4 (0.7%) students. The findings of this study may also be validated in the
      general population. The study concluded that male undergraduate medical students
      are at a high risk for developing snoring habits.

PMID- 22621988
TI  - Effect of CXCR4 inhibitor AMD3100 on alkaline phosphatase activity and
      mineralization in osteoblastic MC3T3-E1 cells.
AB  - The aim of the study was to investigate the effect of C-X-C chemokine receptor
      type 4 (CXCR4) inhibitor AMD3100 on the osteogenic differentiation of pre
      osteoblastic cell line MC3T3-E1. In this study we found that blocking SDF-1/CXCR4
      signaling with AMD3100 strongly suppressed osteogenic differentiation in MC3T3-E1
      cells, as evidenced by an early decrease in the activity of alkaline phosphatase
      (ALP), and down-regulation of mRNA expression of the osteogenic master regulator
      Runx2, ALP, osteocalcin, and progressive ankylosis genes. Moreover, we found that
      the regulatory effect of AMD3100 might be mediated via intracellular STAT3
      activation. However, AMD3100 exerted no significant effect on generation of
      matrix mineralization at the terminal stage of osteogenic induction. In
      conclusion, our results demonstrated an inhibitory role of AMD3100 in osteogenic
      differentiation of MC3T3-E1 cells, especially in the early stage, which provides
      novel insights into the effect of CXCR4 antagonists on modulation of
      osteogenesis.

PMID- 22621989
TI  - Analysis of cytotoxicity induced by proinflammatory cytokines in the human
      alveolar epithelial cell line A549.
AB  - Epithelial cell injury under hyperinflammatory conditions is critical in the
      development of septic acute lung injury (ALI). The aim of the present study is to
      analyze the cytotoxic effects of a mixture of proinflammatory cytokines in the
      human alveolar epithelial cell line A549. The cytotoxicity of proinflammatory
      cytokines were assessed in A549 cells by measuring lactate dehydrogenase released
      into the culture medium and by crystal violet staining of surviving cells.
      Activation of the caspase-dependent apoptotic pathway was evaluated by monitoring
      cleavage of cytokeratin 18 by caspases using enzyme-liked immunosorbent assay
      (ELISA). To estimate the cytotoxic signaling pathways responsible for epithelial
      injury, agents with antiinflammatory or antioxidative properties were extensively
      screened for cytoprotective effects in the inflammation-associated epithelial
      injury model. The present study revealed that inflammatory cytokines exerted
      cytotoxicity in A549 cells. A mixture of interleukin-1beta (IL-1beta), tumor
      necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), designated as
      cytomix, augmented cytotoxicity compared with each individual cytokine. Treatment
      with glucocorticoid (dexamethasone), tetracycline-derived antiinflammatory
      antibiotics (minocycline or doxycycline), angiotensin II receptor blockers
      (losartan or telmisartan), or antioxidants (dimethyl sulfoxide, catalase)
      attenuated cytomix-induced cytotoxicity, including caspase activation. These
      results implied that inflammatory cytokines alone could cause alveolar epithelial
      injury in the pathophysiology of septic ALI. Caspase-dependent apoptosis was
      speculated to be one mechanism responsible for the cytokine-induced cytotoxicity.
      Agents with antiinflammatory or antioxidative properties such as glucocorticoid,
      tetracycline-derived antibiotics, angiotensin II receptor blockers, or direct
      antioxidants showed substantial effect in attenuating cytokine-induced
      cytotoxicity and may be candidates for treatment options.

PMID- 22621990
TI  - N-terminal PEGylation of human serum albumin and investigation of its
      pharmacokinetics and pulmonary microvascular retention.
AB  - Human serum albumin (HSA) is used as an important plasma volume expander in
      clinical practice. In the present study, HSA was N-terminally PEGylated and a
      PEGylated HAS (PEG-HSA) carrying one chain of PEG (20 kDa) per HSA molecule was
      obtained. The purity, secondary structure and hydrodynamic radius of the modified
      protein were characterized using sodium dodecyl sulfate polyacrylamide gel
      electrophoresis, circular dichroism measurements, and dynamic light scattering,
      respectively. The pharmacokinetics in normal mice and vascular permeability of
      the PEG-HSA in a lipopolysaccharide-induced acute lung injury mice model were
      evaluated. The results showed that the biological half-life of the modified HSA
      was approximately 2.2 times of that of native HSA, and PEG-HSA had a lower
      vascular permeability which suggested that PEGylation of HSA could reduce
      extravasation into interstitial space. It can be inferred that due to the
      prolonged half-life time and enhanced vascular retention, the molecularly
      homogeneous PEG-HSA may be a superior candidate as a plasma volume expander in
      treating capillary permeability increase related illness.

PMID- 22621991
TI  - Protective effect of Lysimachia christinae against acute alcohol-induced liver
      injury in mice.
AB  - Lysimachia christinae Hance (Primulaceae) is a medicinal plant. The present study
      was undertaken to investigate protection of L. christinae against acute alcohol
      induced liver injury in mice, the related mechanism of oxidative stress and its
      hepatoprotective chemical compound for the first time. Mice were orally
      administered alcohol at 6 g/kg 2 h after a 75% ethanol extract of L. christinae
      (ET) (100, 200, 400 mg/kg), quercetin (2, 4, 8 mg/kg) isolated from L.
      christinae, or bifendate (150 mg/kg) for seven consecutive days by intragastric
      administration (i.g.) except the normal group. Serum and liver tissue samples
      were collected 6 h after alcohol administration and the amount of quercetin in ET
      was analyzed by high-performance liquid chromatography (HPLC) with a diode array
      detector (DAD). The results showed that alcohol-induced elevated serum alanine
      transferase (ALT) and aspartate transaminase (AST) activities were significantly
      reduced by ET (200, 400 mg/kg), quercetin (4, 8 mg/kg) and bifendate (150 mg/kg),
      respectively. Further analysis demonstrated that lipid peroxidation (LPO) levels
      significantly decreased, while glutathione amounts, glutathione-s transferase
      (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase
      (CAT) activities all increased in livers of ET-, quercetin-, and bifendate
      treated mice. Besides, amount of quercetin in ET was 1.03%. Taken together, our
      results indicate that L. christinae can protect against acute alcohol-induced
      liver injury in mice, the potential mechanism can be related to inhibiting liver
      oxidative stress injury, and its main hepatoprotective compound is quercetin, for
      the first time.

PMID- 22621992
TI  - Intrahepatic cholangiocarcinoma with intrahepatic biliary lithiasis arising 47
      years after the excision of a congenital biliary dilatation: report of a case.
AB  - We report a case of intrahepatic cholangiocarcinoma with biliary lithiasis
      arising 47 years after surgery for a congenital biliary dilatation (CBD). A 62
      year-old woman was admitted for the investigation of a liver tumor. She had
      undergone a choledochoduodenostomy at the age of 15 years for CBD and resection
      of an extrahepatic bile duct with choledochojejunostomy because of cholangitis at
      the age of 55 years. An enhanced computed tomography (CT) revealed a liver tumor
      50 mm in diameter in the S6 region with surrounding lymph node swelling and
      intrahepatic metastatic lesions in the S8 region. A drip infusion
      cholangiographic CT showed biliary lithiases in the left liver. An extended right
      hepatectomy and lymph node dissection was considered but was abandoned because of
      suspicions of liver functional insufficiency as a result of biliary lithiasis.
      She underwent biliary lithotomy through a percutaneous transhepatic
      cholangioscopy and subsequent systemic chemotherapy.

PMID- 22621993
TI  - Blinded measure of Trendelenburg angle in pelvic robotic surgery.
AB  - STUDY OBJECTIVE: To estimate the Trendelenburg angle needed to perform robotic
      gynecologic surgical procedures. DESIGN: Cross-sectional study (Canadian Task
      Force classification III). SETTING: Community hospital. PATIENTS: All women
      undergoing gynecologic pelvic surgery using the da Vinci surgical robot at a
      single institution between December 2010 and April 2011. INTERVENTIONS: The
      primary surgeon determined the Trendelenburg angle needed for adequate
      visualization to perform surgery defined as small bowel and sigmoid colon
      displaced out of the surgical field. MEASUREMENTS AND MAIN RESULTS: The primary
      outcome, measured in blinded fashion, was the degree of Trendelenburg positioning
      needed to complete the surgical procedure robotically. Secondary data collected
      included body mass index, type of surgery performed, maximum end-tidal CO(2), and
      maximum peak inspiratory pressure. Sixteen surgeons performed a total of 104
      robotic gynecologic pelvic surgeries during the study. Data were available for 86
      cases. The mean Trendelenburg angle used was 28.0 degrees (95% confidence
      interval, 26.9-29.1). This was significantly less than the 40 degrees (p < .001)
      commonly recommended. The Trendelenburg angle used did not correlate with body
      mass index (r = -0.2; p = .13) or type of surgery performed (p = .41). Neither
      the maximum end-tidal CO(2) or maximum peak inspiratory pressure was influenced
      by the Trendelenburg angle used when adjusted for age and body mass index.
      CONCLUSIONS: A mean Trendelenburg angle of 28.0 degrees was adequate to complete
      most gynecologic robotic surgical procedures when compared with historical
      control angle of 40 degrees.

PMID- 22621994
TI  - Hysteroscopic treatment of postcesarean scar defect.
AB  - STUDY OBJECTIVE: To estimate the usefulness of hysteroscopy in the diagnosis and
      treatment of postcesarean scar defect. DESIGN: Retrospective study (Canadian Task
      Force classification III). SETTING: Two university-affiliated hospitals.
      PATIENTS: Sixty-two patients with postcesarean scar defects were retrospectively
      analyzed. INTERVENTIONS: All patients with postcesarean scar defects diagnosed
      using ultrasonography and hysteroscopy underwent hysteroscopic surgery, and were
      followed up for longer than 1 year. MEASUREMENTS AND MAIN RESULTS: Hysteroscopy
      revealed that 38 patients had valve-like motions at the incision sites, 22 had
      dome-like defects, and 2 with a history of 2 previous deliveries via cesarean
      section had umbilications of 2 different shades. Fifty-seven of 62 patients
      underwent corrective surgery via hysteroscopy. In another 3 patients, because the
      left wall of the fundus of the uterus was too thin (<2 mm at ultrasonography) to
      undergo corrective surgery, only clearance of residual blood and/or suture
      materials was performed. Of these 57 patients, 5 underwent removal of residual
      suture materials and endometrial fulguration. No complications were observed in
      these patients. Furthermore, after surgery, abnormal vaginal bleeding stopped in
      38 patients, and its duration was shortened in 20 patients. In addition,
      dysmenorrhea was alleviated in 15 patients, and resolved in 7 patients.
      CONCLUSION: Hysteroscopy is an accurate means of diagnosis apart from surgical
      correction.

PMID- 22621995
TI  - Everyday action impairment in Parkinson's disease dementia.
AB  - This study examined everyday action impairment in participants with Parkinson's
      disease dementia (PDD) by comparison with participants with Parkinson's disease
      no dementia (PD) or Alzheimer's disease (AD) and in reference to a
      neuropsychological model. Participants with PDD (n = 20), PD (n = 20), or AD (n =
      20) were administered performance-based measures of everyday functioning that
      allowed for the quantification of overall performance and error types. Also,
      caregiver ratings of functional independence were obtained. On performance-based
      tests, the PDD group exhibited greater functional impairment than the PD group
      but comparable overall impairment relative to the AD group. Error patterns did
      not differ between PDD and PD participants but the PDD group demonstrated a
      higher proportion of commission errors and lower proportion of omission errors
      relative to the AD group. Hierarchical regression analyses showed omission errors
      were significantly predicted by neuropsychological measures of episodic memory,
      whereas commission errors were predicted by both measures of general dementia
      severity (MMSE) and executive control. Everyday action impairment in PDD differs
      quantitatively from PD but qualitatively from AD and may be characterized by a
      relatively high proportion of commission errors-an error type associated with
      executive control deficits. (JINS, 2012, 18, 1-12).

PMID- 22621996
TI  - Consumer preferences for household water treatment products in Andhra Pradesh,
      India.
AB  - Over 5 billion people worldwide are exposed to unsafe water. Given the obstacles
      to ensuring sustainable improvements in water supply infrastructure and the
      unhygienic handling of water after collection, household water treatment and
      storage (HWTS) products have been viewed as important mechanisms for increasing
      access to safe water. Although studies have shown that HWTS technologies can
      reduce the likelihood of diarrheal illness by about 30%, levels of adoption and
      continued use remain low. An understanding of household preferences for HWTS
      products can be used to create demand through effective product positioning and
      social marketing, and ultimately improve and ensure commercial sustainability and
      scalability of these products. However, there has been little systematic research
      on consumer preferences for HWTS products. This paper reports the results of the
      first state-of-the-art conjoint analysis study of HWTS products. In 2008, we
      conducted a conjoint analysis survey of a representative sample of households in
      Andhra Pradesh (AP), India to elicit and quantify household preferences for
      commercial HWTS products. Controlling for attribute non-attendance in an error
      components mixed logit model, the study results indicate that the most important
      features to respondents, in terms of the effect on utility, were the type of
      product, followed by the extent to which the product removes pathogens, the
      retail outlet and, the time required to treat 10 L. Holding all other product
      attributes constant, filters were preferred to combination products and chemical
      additives. Department stores and weekly markets were the most favorable sales
      outlets, followed by mobile salespeople. In general, households do not prefer to
      purchase HWTS products at local shops. Our results can inform the types of
      products and sales outlets that are likely to be successful in commercial HWTS
      markets in AP, as well as the influence of different pricing and financing
      strategies on product demand and uptake.

PMID- 22621997
TI  - Systematic meta-analysis of insula volume in schizophrenia.
AB  - BACKGROUND: Volume reduction in insular cortex may constitute an important
      neuropathology in schizophrenia. We provide the first meta-analysis of studies
      that conducted region-of-interest analyses of the magnitude of effect and pattern
      of insula volume reduction in schizophrenia compared with healthy control
      subjects. METHODS: Included studies examined insula volume in schizophrenia
      relative to healthy control subjects. Studies were located via electronic
      database searches and hand searching. Study selection, data extraction, and
      quality assessment were completed by two independent reviewers. Hedge's g effect
      sizes were calculated using Comprehensive Meta-Analysis (v.2) to quantify
      volumetric differences between people with and without schizophrenia, accounting
      for moderating influences of age, sex, illness duration, medication, whole brain
      volume, and potential differences in hemispheric and anatomical subregions.
      RESULTS: Random-effects analysis showed reductions of bilateral insula (n = 945,
      g = -.446, 95% confidence interval -.639 to -.252, p = .00001), with moderate
      heterogeneity apparent (I2 = 76%). This effect was consistent across left and
      right insula and not influenced by illness stage or sex. Additional analyses
      revealed larger reductions of anterior (n = 605, g = -.643, p < 0.001; I2 = 52%)
      than of posterior insula (n = 453, g = -.321, p = .028; I2 = 55%). Meta
      regression analyses did not identify any significant predictors of reduced insula
      volume. CONCLUSIONS: This meta-analysis indicates medium-sized reduction of
      insula volume in schizophrenia, of greatest magnitude in the anterior subregion.
      Cellular distinctions across anterior and posterior insula may contribute to
      understanding the neuropathology and functional significance of the observed
      volumetric differences.

PMID- 22621998
TI  - Dynamics of defensive reactivity in patients with panic disorder and agoraphobia:
      implications for the etiology of panic disorder.
AB  - BACKGROUND: The learning perspective of panic disorder distinguishes between
      acute panic and anxious apprehension as distinct emotional states. Following
      animal models, these clinical entities reflect different stages of defensive
      reactivity depending upon the imminence of interoceptive or exteroceptive threat
      cues. The current study tested this model by investigating the dynamics of
      defensive reactivity in a large group of patients with panic disorder and
      agoraphobia (PD/AG). METHODS: Three hundred forty-five PD/AG patients
      participated in a standardized behavioral avoidance test (being entrapped in a
      small, dark chamber for 10 minutes). Defense reactivity was assessed measuring
      avoidance and escape behavior, self-reports of anxiety and panic symptoms,
      autonomic arousal (heart rate and skin conductance), and potentiation of the
      startle reflex before and during exposure of the behavioral avoidance test.
      RESULTS: Panic disorder and agoraphobia patients differed substantially in their
      defensive reactivity. While 31.6% of the patients showed strong anxious
      apprehension during this task (as indexed by increased reports of anxiety,
      elevated physiological arousal, and startle potentiation), 20.9% of the patients
      escaped from the test chamber. Active escape was initiated at the peak of the
      autonomic surge accompanied by an inhibition of the startle response as predicted
      by the animal model. These physiological responses resembled the pattern observed
      during the 34 reported panic attacks. CONCLUSIONS: We found evidence that
      defensive reactivity in PD/AG patients is dynamically organized ranging from
      anxious apprehension to panic with increasing proximity of interoceptive threat.
      These data support the learning perspective of panic disorder.

PMID- 22621999
TI  - Simple viewing tests can detect eye movement abnormalities that distinguish
      schizophrenia cases from controls with exceptional accuracy.
AB  - BACKGROUND: We have investigated which eye-movement tests alone and combined can
      best discriminate schizophrenia cases from control subjects and their predictive
      validity. METHODS: A training set of 88 schizophrenia cases and 88 controls had a
      range of eye movements recorded; the predictive validity of the tests was then
      examined on eye-movement data from 34 9-month retest cases and controls, and from
      36 novel schizophrenia cases and 52 control subjects. Eye movements were recorded
      during smooth pursuit, fixation stability, and free-viewing tasks. Group
      differences on performance measures were examined by univariate and multivariate
      analyses. Model fitting was used to compare regression, boosted tree, and
      probabilistic neural network approaches. RESULTS: As a group, schizophrenia cases
      differed from control subjects on almost all eye-movement tests, including
      horizontal and Lissajous pursuit, visual scanpath, and fixation stability;
      fixation dispersal during free viewing was the best single discriminator. Effects
      were stable over time, and independent of sex, medication, or cigarette smoking.
      A boosted tree model achieved perfect separation of the 88 training cases from 88
      control subjects; its predictive validity on retest assessments and novel cases
      and control subjects was 87.8%. However, when we examined the whole data set of
      298 assessments, a cross-validated probabilistic neural network model was
      superior and could discriminate all cases from controls with near perfect
      accuracy at 98.3%. CONCLUSIONS: Simple viewing patterns can detect eye-movement
      abnormalities that can discriminate schizophrenia cases from control subjects
      with exceptional accuracy.

PMID- 22622001
TI  - Heart rate achieved or beta-blocker dose in patients with chronic heart failure:
      which is the better target?
AB  - AIMS: To investigate whether the mortality of patients with chronic heart failure
      (CHF) due to left ventricular systolic dysfunction (LVSD) is more strongly
      related to beta-blocker dose or to heart rate. It is known that beta-blockers
      reduce mortality in patients with CHF and LVSD, but the primary mechanism of
      action is uncertain. METHODS AND RESULTS: Patients with an ejection fraction
      <=40%, who were in sinus rhythm both at an initial (visit 1) and at a 4-month
      clinic review (visit 2), were followed for a maximum of 36 months. The
      relationships between heart rate, beta-blocker dose, and survival in a
      multivariable model were examined. Of 654 eligible patients, 381 (58%) were
      started on beta-blockers prior to the initial visit, increasing to 537 (82%) by
      visit 2. During follow-up, 142 (22%) patients died. Neither resting heart rate
      nor beta-blocker dose at visit 1 predicted mortality (P = 0.09 and P = 0.99), but
      resting heart rate at visit 2 did (P = 0.02). Beta-blocker use at visit 2 was
      associated with better outcome (P = 0.03) but with little variation in outcome
      according to dose. Patients with a heart rate of 58-64 b.p.m. at visit 2 had the
      best prognosis. CONCLUSIONS: The use of beta-blockers and resting heart rate at
      visit 2 both independently indicated prognosis, but beta-blocker dose did not.
      Beta-blockers may reduce mortality by several mechanisms; one that may be
      specific to blockade of adrenergic receptors and another related to heart rate
      reduction. Achieving a target heart rate range may be an appropriate therapeutic
      goal for patients with CHF.

PMID- 22622000
TI  - Male germline transmits fetal alcohol adverse effect on hypothalamic
      proopiomelanocortin gene across generations.
AB  - BACKGROUND: Neurons containing proopiomelanocortin (POMC)-derived peptides, known
      to control stress axis, metabolic, and immune functions, have a lower function in
      patients with a family history of alcoholism, raising the possibility that
      alcohol effects on the POMC system may transmit through generations. Here we
      describe epigenetic modifications of Pomc gene that transmit through generation
      via male germline and may be critically involved in alcoholism-inherited
      diseases. METHODS: Whether an epigenetic mechanism is involved in causing a Pomc
      expression deficit in fetal alcohol-exposed rats is studied by determining Pomc
      gene methylation, expression, and functional abnormalities and their
      normalization following suppression of DNA methylation or histone acetylation.
      Additionally, transgenerational studies were conducted to evaluate the germline
      transmitted effect of alcohol. RESULTS: Fetal alcohol-exposed male and female rat
      offspring showed a significant deficit in POMC neuronal functions. Associated
      with this was an increased methylation status of several CpG dinucleotides in the
      proximal part of the Pomc promoter region and altered level of histone-modifying
      proteins and DNA methyltransferases levels in POMC neurons. Suppression of
      histone deacetylation and DNA methylation normalized Pomc expression and
      functional abnormalities. Fetal alcohol-induced Pomc gene methylation,
      expression, and functional defects persisted in the F2 and F3 male but not in
      female germline. Additionally, the hypermethylated Pomc gene was detected in
      sperm of fetal alcohol-exposed F1 offspring that was transmitted through F3
      generation via male germline. CONCLUSIONS: Trangenerational epigenetic studies
      should spur new insight into the biological mechanisms that influence the sex
      dependent difference in genetic risk of alcoholism-inherited diseases.

PMID- 22622002
TI  - Alterations in aortic wave reflection with vasodilation and vasoconstriction in
      anaesthetized dogs.
AB  - BACKGROUND: Using the reservoir-wave approach, we studied wave propagation,
      reflection, and re-reflection in the canine aorta with administrations of sodium
      nitroprusside (NP) and methoxamine (Mtx). METHODS: In 8 anaesthetized dogs,
      excess pressures were calculated from pressure and flow measurements at 4
      locations along the aorta; wave intensity analysis was employed to identify
      wavefronts and the type of waves. RESULTS: NP (intravenous; 14 MUg/min) decreased
      mean aortic pressure from 80 +/- 3 mm Hg to 48 +/- 1 mm Hg; Mtx (intravenous; 10
      MUg/min) increased mean pressure from 80 +/- 3 mm Hg to 104 +/- 4 mm Hg. NP
      increased negative reflection near the kidneys (reflection coefficient: -0.33 vs 
      0.18; P < 0.01) and produced new negatively reflecting sites just beyond the arch
      and in the proximal femoral arteries, consistent with a vasodilating effects of
      nitrates on conducting arteries. Mtx negated negative reflection from near the
      kidneys (-0.02 vs -0.17; P < 0.01) and increased positive femoral reflection
      (0.38 vs 0.26; P < 0.01). The large reflected compression wave was re-reflected
      from the closed aortic valve to produce a prominent increase in middiastolic
      pressure in the distal aorta. CONCLUSIONS: The reservoir-wave approach explains
      decreasing diastolic pressure without positing waves that travel at near-infinite
      velocities and reveals the pressure changes that are uniquely due to wave motion.

PMID- 22622003
TI  - Fatal late migration of viacor percutaneous transvenous mitral annuloplasty
      device resulting in distal coronary venous perforation.
AB  - We present the case of a patient with dilated ischemic cardiomyopathy and severe
      mitral regurgitation. Due to several comorbidities, he underwent percutaneous
      transvenous mitral annuloplasty. Postoperatively, he complained of atypical chest
      pain. He was treated for pericarditis and died suddenly 10 days after the
      procedure. Autopsy showed distal perforation of the anterior interventricular
      vein with migration of the device on the diaphragm.

PMID- 22622004
TI  - The acceptability of treatments for depression to a community sample of
      adolescent girls.
AB  - An efficacious treatment is diminished in value if consumers do not seek it out
      and adhere to it, making treatment acceptability an important predictor of the
      effectiveness of treatment. This study examined the acceptability of treatments
      for depression to 67 female high school students. All participants read a
      vignette describing a depressed adolescent and rated the acceptability of four
      single treatments for depression (cognitive-behavioral therapy, interpersonal
      therapy, family therapy, and pharmacotherapy) and three treatment combinations.
      Psychotherapy approaches were generally more acceptable to adolescents than
      combinations of psychotherapy and pharmacotherapy; and, pharmacotherapy used
      alone was not acceptable. For interpersonal therapy and family therapy only,
      treatment acceptability was related to perceived causes of depression. Across all
      treatments, acceptability was not associated with symptom severity. Implications
      for increasing the utilization of mental health services in this population are
      discussed.

PMID- 22622006
TI  - Use of rocuronium and sugammadex for caesarean delivery in a patient with
      myasthenia gravis.

PMID- 22622007
TI  - Attacking tumor cells with a dual ligand for innate immune receptors.

PMID- 22622008
TI  - Thoracic radiotherapy with or without daily low-dose carboplatin in elderly
      patients with non-small-cell lung cancer: a randomised, controlled, phase 3 trial
      by the Japan Clinical Oncology Group (JCOG0301).
AB  - BACKGROUND: It is unknown whether combined chemoradiotherapy improves overall
      survival in elderly patients with locally advanced non-small-cell lung cancer
      (NSCLC). The aim of this study was to assess whether radiotherapy plus
      carboplatin results in longer survival than radiotherapy alone in elderly
      patients with NSCLC. METHODS: This was a randomised, controlled, phase 3 trial by
      the Japan Clinical Oncology Group (JCOG0301). Patients older than 70 years with
      unresectable stage III NSCLC were randomly assigned to chemoradiotherapy (60 Gy
      plus concurrent low-dose carboplatin [30 mg/m(2) per day, 5 days a week for 20
      days]) or radiotherapy alone, using a minimisation method with biased-coin
      assignment balancing on Eastern Cooperative Oncology Group (ECOG) performance
      status (0 vs 1 vs 2), stage (IIIA vs IIIB), and institution. The primary endpoint
      was overall survival, which was analysed for the eligible population and
      stratified by ECOG performance status, stage, and institution. The trial was
      stopped early as a result of the second planned interim analysis. This study is
      registered with UMIN Clinical Trials Registry, number C000000060, and
      ClinicalTrials.gov, number NCT00132665. FINDINGS: 200 patients were enrolled from
      Sept 1, 2003 to May 27, 2010: 100 in the chemoradiotherapy group and 100 in the
      radiotherapy group. The second planned interim analysis was done 10 months after
      completion of patient accrual. At this time, median follow-up for censored cases
      was 19.4 months (IQR 10.3-33.5). In accordance with the prespecified stopping
      rule, the JCOG data and safety monitoring committee recommended early publication
      of this trial because the difference in overall survival favoured the
      chemoradiotherapy group. Median overall survival for the chemoradiotherapy and
      radiotherapy alone groups were 22.4 months (95% CI 16.5-33.6) and 16.9 months
      (13.4-20.3), respectively (hazard ratio 0.68, 95.4% CI 0.47-0.98, stratified log
      rank test one-sided p value=0.0179). More patients had grade 3-4 haematological
      toxic effects in the chemoradiotherapy group than in the radiotherapy alone
      group, including leucopenia (61 [63.5%] vs none), neutropenia (55 [57.3%] vs
      none), and thrombocytopenia (28 [29.2%] vs two [2.0%]). Grade 3 infection was
      more common with chemoradiotherapy (12 patients [12.5%]) than with radiotherapy
      (four patients [4.1%]). Incidences of grade 3-4 pneumonitis and late lung
      toxicity were similar between groups. There were seven treatment-related deaths:
      three of 100 patients (3.0%) in the chemoradiotherapy group and four of 100
      (4.0%) in the radiotherapy group. INTERPRETATION: For a select group of elderly
      patients with locally advanced NSCLC, combination chemoradiotherapy provides a
      clinically significant benefit over radiotherapy alone, and should be considered
      for this population. FUNDING: Ministry of Health, Labour, and Welfare of Japan.

PMID- 22622009
TI  - Treating elderly patients with stage III NSCLC.

PMID- 22622010
TI  - Molecular basis of the initial platelet adhesion in arterial thrombosis:
      molecular dynamics simulations.
AB  - Molecular interactions between the von Willebrand factor (VWF) A1 domain and
      glycoprotein Ibalpha (GPIbalpha) promote the initial adhesion of platelets and
      subsequent arterial thrombus formation. However, little is understood about the
      interactions at a molecular level. Therefore, the binding dynamics and involved
      molecular interactions between VWF A1 domain and GPIbalpha in both water and
      physiological saline are investigated using molecular dynamics simulations and
      all-atom models. Faster binding is observed in water than that in physiological
      saline, and patches of opposite charges are observed at the binding interface.
      Moreover, molecular mechanics-Poisson-Boltzmann surface area analysis indicates
      that the binding is promoted by the long-range electrostatic interactions and
      then maintained by hydrophobic interactions. For the initial binding, the hot
      spots include the residues E14, E128, D175, D83, E151, D106, D63, E5, D18, E225,
      D235 in GPIbalpha, and K608, K569, K644, R571, K572, R636, K599 in VWF A1 domain.
      For the final complex formation, however, 72% of the favorable contributions are
      from hydrophobic interactions. The results provided molecular insight into the
      initial platelet adhesion. The hot spots identified would be beneficial for
      developing novel drugs for thrombotic diseases.

PMID- 22622011
TI  - Calculating the Na+ translocating V-ATPase catalytic site affinity for substrate
      binding by homology modeled NtpA monomer using molecular dynamics/free energy
      calculation.
AB  - Vacuolar ATPase (V-ATPase) of Enterococcus hirae is composed of a soluble
      catalytic domain (V1; NtpA3-B3-D-G) and an integral membrane domain (V0; NtpI
      K10) connected by a central and two peripheral stalks (NtpC, NtpD-G and NtpE-F).
      Recently nucleotide binding of catalytic NtpA monomer has been reported (Arai et
      al.). In the present study, we calculated the nucleotide binding affinity of NtpA
      by molecular dynamics (MD) simulation/free energy calculation using MM-GBSA
      approach based on homology modeled structure of NtpA monomer docked with ATP
      analogue, adenosine 5'-[beta, gamma-imido] triphosphate (AMP-PNP). The calculated
      binding free energies showed qualitatively good agreement with experimental data.
      The calculation was cross-validated further by the rigorous method, thermodynamic
      integration (TI) simulation. Finally, the interaction between NtpA and
      nucleotides at the atomic level was investigated by the analyses of components of
      free energy and the optimized model structures obtained from MD simulations,
      suggesting that electrostatic contribution is responsible for the difference in
      nucleotide binding to NtpA monomer. This is the first observation and suggestion
      to explain the difference of nucleotide binding properties in V-ATPase NtpA
      subunit, and our method can be a valuable primary step to predict nucleotide
      binding affinity to other subunits (NtpAB, NtpA3B3) and to explore subunit
      interactions and eventually may help to understand energy transduction mechanism
      of E. hirae V-ATPase.

PMID- 22622012
TI  - Pharmacophore identification, docking and "in silico" screening for novel CDK1
      inhibitors.
AB  - Pharmacophore models of cyclin-dependent kinase-1 (CDK1) inhibitors were
      established by using the Catalyst/HypoGen. The best pharmacophore model, Hypo1,
      consists of one hydrogen bond acceptor (HBA), one hydrogen bond donor (HBD), one
      hydrophobic (HY) and one ring aromatic (RA) feature. The validation results of
      Hypo1 through cost analysis, test set prediction, Fisher's cross method and
      receiver operating characteristic (ROC) study indicated that the Hypo1 was
      statistically valuable and reliable in identifying structural diverse CDK1
      inhibitors. It is further supported by the consistent results from molecular
      docking studies. Finally, the Hypo1 was used to "in silico" screen the NCI and
      MayBridge database. The preferable hits obtained were further docked into ATP
      binding site of CDK1, and nine promising compounds were retrieved as novel
      potential CDK1 inhibitors for further studies.

PMID- 22622013
TI  - Aquatic ecotoxicity of the fungicide pyrimethanil: effect profile under optimal
      and thermal stress conditions.
AB  - The aquatic ecotoxic profile of the fungicide pyrimethanil and its acute and
      chronic thermal dependence in two aquatic invertebrates Chironomus riparius and
      Daphnia magna were investigated. The ecotoxicity of pyrimethanil at optimal
      thermal conditions did not depend on the trophic level, but was species-specific.
      The acute pyrimethanil-toxicity on C. riparius increased with higher temperature.
      The chronic response of Daphnia magna to the NOEC of the fungicide was examined
      in a multigenerational experiment under three near-natural temperature regimes. A
      pyrimethanil-induced increase of total mortality was buffered by the strongly
      related increase of the general reproductive capacity, while population growth
      was stronger influenced by temperature than by the fungicide. At a LOEC, however,
      a second generation could not be established with D. magna at all thermal
      regimes. This clearly shows that thermal and multigenerational effects should be
      considered when appraising the ecotoxicity of pesticides and assessing their
      future risk for the environment.

PMID- 22622014
TI  - Up-frameshift protein 1 (UPF1): multitalented entertainer in RNA decay.
AB  - Up-frameshift protein 1 (UPF1) is an evolutionarily conserved protein with
      RNA/DNA-dependent ATPase and RNA helicase activity. The protein is well known for
      its central role in nonsense-mediated mRNA decay (NMD), which eliminates aberrant
      mRNAs harboring premature termination codon (PTC), preventing the accumulation of
      nonfunctional or potentially harmful truncated proteins. NMD is also involved in
      the regulation of the state-levels of many normal physiological mRNAs. Moreover
      UPF1 is not only a key player in NMD but is also involved in non-NMD RNA
      degradation, such as staufen1 (STAU1)-mediated mRNA decay (SMD) and replication
      dependent histone mRNA decay. Thus, UPF1 is an important factor for the RNA
      quality control system and the regulation of physiological gene expression.
      Further, recent studies have clarified that UPF1 contributes to DNA replication,
      DNA repair, telomere metabolism, and stabilization of HIV-1 genomic RNA. In the
      review, we summarize numerous functions of UPF1.

PMID- 22622015
TI  - A facile method for the synthesis of N-(alpha-aminoacyl) sulfonamides.
AB  - N-Acylsulfonamide derivatives have important applications in organic synthesis
      and drug discovery. It was found that many problems occurred preparing amino acid
      derived N-acylsulfonamides with the commonly used coupling approach in our
      previous studies. In this paper, we report an efficient approach to synthesize
      various amino acids derived N-acylsulfonamides in high yields without any
      racemization.

PMID- 22622016
TI  - In silico ligand based design of indolylpiperidinyl derivatives as novel
      histamine H(1) receptor antagonists.
AB  - Histamine H(1) receptor antagonists play a vital role in the first line treatment
      of a broad range of allergic diseases. Frequent dosing of the antagonist results
      in side effects like sedation and cardiovascular toxicity. The present study
      highlights the important structural requirement and mechanistic interpretation of
      novel indolylpiperidinyl derivatives as H(1) receptor antagonists so as to
      facilitate the design of newer antihistaminics with increased duration of action
      and comparatively reduced side effects. The significance of the developed
      quantitative structure-activity relationship (QSAR) models were evaluated on the
      basis of statistical values of square of correlation coefficient (r(2));
      (multiple linear regression (MLR), 0.86; and partial least squares (PLS), 0.85).
      The predictive ability of the resulting QSAR models was evaluated with cross
      validated correlation coefficient (r(2)cv) values (MLR, 0.82; PLS, 0.82)
      generated for the training set and r(2) values (MLR, 0.763; PLS, 0.855) derived
      for test set. The final models comprised of multidimensional steric (verloop
      length, verloop B(3)), electronic (total dipole moment) and steric (KAlpha1
      index) descriptors. The study indicates that antihistaminic activity is largely
      explained by steric and electronic parameters. In line with parameters entered in
      the model some indolylpiperidines derivatives were designed with good
      antihistaminic properties and pharmacokinetic profiles.

PMID- 22622017
TI  - Synthesis, analgesic, anti-inflammatory and ulcerogenic properties of some novel
      N'-((1-(substituted amino)methyl)-2-oxoindolin-3-ylidene)-4-(2-(methyl/phenyl)-4
      oxoquinazolin-3(4H)-yl)benzohydrazide derivatives.
AB  - A new series of N'-((1-(substituted amino)methyl)-2-oxoindolin-3-ylidene)-4-(2
      (methyl/phenyl)-4-oxoquinazolin-3(4H)-yl)benzohydrazide derivatives 4a-4l were
      designed and synthesized from anthranilic acid. All the synthesized compounds
      were characterized by spectroscopic means and elemental analyses. The tail-flick
      technique and the carrageenan-induced foot paw edema test were performed for
      screening analgesic and anti-inflammatory activity, respectively. All of the
      compounds were also examined for their ulcerogenicity. Some of the compounds
      showed significant activity. Among the test compounds, 4b exhibited 53% and 69%
      analgesic activity at a dose of 10 and 20 mg/kg, respectively. It also displayed
      47% (10 mg/kg) and 65% (20 mg/kg) anti-inflammatory activity with one-fourth of
      ulcer index of the reference drugs diclofenac and aspirin.

PMID- 22622018
TI  - Evaluation of innate immune stimulating activity of polysaccharides using a
      silkworm (Bombyx mori) muscle contraction assay.
AB  - In silkworm larvae, the mature form of paralytic peptide (PP), an insect
      cytokine, is produced from pro-PP in association with activation of innate immune
      responses, resulting in slow muscle contraction. We utilized this reaction,
      muscle contraction in silkworms coupled with innate immunity stimulation, to
      quantitatively measure the innate immune stimulating activity of various natural
      polysaccharides. beta-Glucan of Gyrophora esculenta (GE-3), fucoidan from
      sporophyll of Undaria pinnatifida, and curldan induced silkworm muscle
      contraction. We further demonstrated that GE-3 had therapeutic effects on
      silkworms infected by baculovirus. Based on these findings, we propose that the
      silkworm muscle contraction assay is useful for screening substances that
      stimulate innate immunity before evaluating therapeutic effectiveness in mammals.

PMID- 22622019
TI  - Regulation of Janus-activated kinase-2 (JAK2) by diindolylmethane in ovarian
      cancer in vitro and in vivo.
AB  - Janus-activated kinase-2 (JAK2) plays an important role in the activation of
      signal transducer and activation of transcription 3 (STAT3), which is over
      expressed in majority of ovarian tumors. We have reported previously that
      diindolylmethane (DIM) induces apoptosis in ovarian cancer cells by inhibiting
      STAT3. However, the role of JAK2 in our model was not yet understood and hence
      evaluated in this report. SKOV-3 human ovarian cancer cells were used to evaluate
      concentration and time dependent effects of DIM. Interleukin 3 (IL-3) and
      epidermal growth factor (EGF) were used to activate JAK2. Tumor xenograft studies
      were used to determine modulation of JAK2 in vivo. DIM treatment blocked the
      phosphorylation of JAK2 at Tyr-1007 in a concentration-dependent manner. In a
      time-dependent study, inhibition of JAK2 by DIM was as early as 1 h, which was
      followed by the inhibition of STAT3 and survivin. IL-3-induced phosphorylation of
      JAK2 and STAT3 was significantly blocked by DIM. IL-3 treatment blocked DIM
      induced apoptosis. EGF treatment resulted in the activation of JAK2 and STAT3 but
      suppressed by DIM. These results indicate the involvement of cytokines and growth
      factors in the activation of JAK2/STAT3 and that DIM suppress their activation.
      Furthermore, DIM in combination with cisplatin drastically reduced the
      phosphorylation of JAK2 when compared to cisplatin alone. Western blot analysis
      of tumors from DIM treated mice showed significant inhibition of JAK2 activation
      as compared with controls. These findings provide a rationale for further
      clinical investigation of DIM for its potential use alone or in combination with
      chemotherapy of ovarian cancer.

PMID- 22622020
TI  - Analyzing global trends of biomarker use in drug interventional clinical studies.
AB  - The trend of biomarker use in drug interventional clinical studies was analyzed
      using ClinicalTrials.gov to provide an overview of how biomarkers are used to
      streamline clinical studies and to examine regional differences. A total of 3,383
      clinical study data was analyzed according to phase, region, sponsor, and
      therapeutic class. The number of clinical studies using biomarkers has been
      increasing constantly and is dependent on the number of Phase I and II studies.
      The majority of studies (58.5%) were sponsored by the United States, with the
      studies being conducted mainly in the sponsor's home region (80.3%). The use of
      biomarkers was prominent in the oncology area (37.1%). Although current data
      indicates some bias in the clinical use of biomarkers, it is expected that their
      use will increase in later phase studies or other therapeutic areas as biomarker
      development proceeds. In addition, limited regional use of biomarkers may lead to
      differences in biomarker use in drug development and in combination with
      political support may result in differences in competitiveness of drug
      development. Biomarkers would be a powerful tool against deteriorating research
      and development productivity when used more in appropriate clinical study
      conditions.

PMID- 22622021
TI  - Standardization of perioperative management on hepato-biliary-pancreatic surgery.
AB  - Japan-China Joint Medical Workshop (2012) on standardization of perioperative
      management on hepato-biliary-pancreatic surgery was held by the Center for
      Medical Standards Research, IRCA-BSSA Group in Japan on April 15-16, 2012.
      Experts in the fields of surgery, anesthesia, pharmacy, and public health from 21
      health institutions from Japan and China presented their research achievements
      and shared their medical experience of perioperative management on hepato-biliary
      pancreatic surgery, which should facilitate building of guidelines for
      hepatocellular carcinoma and be expected to promote standardized management of
      liver cancer in Asia.

PMID- 22622023
TI  - Thyrotropin and thyroid cancer diagnosis: a systematic review and dose-response
      meta-analysis.
AB  - CONTEXT: TSH is the major growth factor for thyrocytes and may have a causative
      role in thyroid cancer. OBJECTIVE: The objective of the study was to
      systematically assess the association between serum TSH and thyroid cancer. DATA
      SOURCES: The MEDLINE and EMBASE databases were searched using synonyms for TSH
      and thyroid cancer, supplemented with reference list searches and author contact.
      STUDY SELECTION: Prospective cohort, case-control, and cross-sectional studies
      were identified with TSH the exposure and thyroid cancer the outcome. DATA
      EXTRACTION: Three reviewers independently extracted data. Studies reporting odds
      ratio (OR) for TSH levels and thyroid cancer were analyzed via meta-analysis and
      generalized least-squares trend estimation for dose-response relationships. DATA
      SYNTHESIS: Data extracted from 28 studies included a total of 42,032 subjects and
      5,786 thyroid cancer cases. Dose-response spline analysis revealed a nonlinear
      relationship (P < 0.001). For TSH levels less than 1 mU/liter, the OR for thyroid
      cancer was 1.72 (1.42, 2.07) per milliunits per liter. However, the relationship
      changed for TSH levels 1 mU/liter and greater, with the OR thereafter being 1.16
      (1.12, 1.21) per milliunits per liter. Studies controlling for autoimmunity
      reported the lowest OR [TSH below 2.5 mU/liter, OR 1.23 (1.02-1.47) per
      milliunits per liter; TSH 2.5 mU/liter or greater, OR 0.98 (0.89-1.09) per
      milliunits per liter]. Six groups assessed serum TSH in relation to markers of
      poor thyroid cancer prognosis, with three showing significant positive
      relationships. CONCLUSIONS: Higher serum TSH concentration is associated with an
      increased risk of thyroid cancer. Thyroid autoimmunity may partially explain the
      association, but further epidemiological assessment is required. Future clinical
      research should investigate the validity of including serum TSH in diagnostic
      nomograms, its prognostic importance, and the potential for therapeutic TSH
      suppression in thyroid cancer prevention.

PMID- 22622022
TI  - Event-related functional magnetic resonance imaging changes during relational
      retrieval in normal aging and amnestic mild cognitive impairment.
AB  - The earliest cognitive deficits observed in amnestic mild cognitive impairment
      (aMCI) appear to center on memory tasks that require relational memory (RM), the
      ability to link or integrate unrelated pieces of information. RM impairments in
      aMCI likely reflect neural changes in the medial temporal lobe (MTL) and
      posterior parietal cortex (PPC). We tested the hypothesis that individuals with
      aMCI, as compared to cognitively normal (CN) controls, would recruit neural
      regions outside of the MTL and PPC to support relational memory. To this end, we
      directly compared the neural underpinnings of successful relational retrieval in
      aMCI and CN groups, using event-related functional magnetic resonance imaging
      (fMRI), holding constant the stimuli and encoding task. The fMRI data showed that
      the CN, compared to the aMCI, group activated left precuneus, left angular gyrus,
      right posterior cingulate, and right parahippocampal cortex during relational
      retrieval, while the aMCI group, relative to the CN group, activated superior
      temporal gyrus and supramarginal gyrus for this comparison. Such findings
      indicate an early shift in the functional neural architecture of relational
      retrieval in aMCI, and may prove useful in future studies aimed at capitalizing
      on functionally intact neural regions as targets for treatment and slowing of the
      disease course. (JINS, 2012, 18, 1-12).

PMID- 22622024
TI  - Pediatric pulmonary arterial hypertension and hyperthyroidism: a potentially
      fatal combination.
AB  - CONTEXT: Patients with pulmonary arterial hypertension (PAH) who develop
      hyperthyroidism are at risk for acute cardiopulmonary decompensation and death.
      CASES AND SETTING: We present a series of eight idiopathic PAH/heritable PAH
      pediatric patients who developed hyperthyroidism between 1999 and 2011.
      Institutional Review Board approval was obtained; informed consent was waived due
      to the retrospective nature of the series. All eight patients were receiving iv
      epoprostenol; five of the eight patients presented with acute cardiopulmonary
      decompensation in the setting of hyperthyroidism. In the remaining three
      patients, hyperthyroidism was detected during routine screening of thyroid
      function tests. The one patient who underwent emergency thyroidectomy was the
      only survivor of those who presented in cardiopulmonary decline. EVIDENCE
      SYNTHESIS: Aggressive treatment of the hyperthyroid state, including emergency
      total thyroidectomy and escalation of targeted PAH therapy and beta-blockade when
      warranted, may prove lifesaving in these patients. Prompt thyroidectomy or
      radioactive iodine ablation should be considered for clinically stable PAH
      patients with early and/or mild hyperthyroidism to avoid potentially life
      threatening cardiopulmonary decompensation. CONCLUSIONS: Although the association
      between hyperthyroidism and PAH remains poorly understood, the potential impact
      of hyperthyroidism on the cardiopulmonary status of PAH patients must not be
      ignored. Hyperthyroidism must be identified early in this patient population to
      optimize intervention before acute decompensation. Thyroid function tests should
      be checked routinely in patients with PAH, particularly those on iv epoprostenol,
      and urgently in patients with acute decompensation or symptoms of
      hyperthyroidism.

PMID- 22622025
TI  - Adrenal myelolipoma: an unusual cause of bilateral highly 18F-FDG-avid adrenal
      masses.

PMID- 22622026
TI  - PCR detection of Burkholderia cepacia complex as one of key factors to handle a
      long-term outbreak.
AB  - BACKGROUND: Once the outbreak with Burkholderia cenocepacia ST32 was identified
      in the Prague cystic fibrosis (CF) centre, molecular tools were implemented into
      diagnostic routine in order to complement infection control measures with as
      accurate as possible microbiological service. In addition, genotyping techniques
      were applied as part of an infection surveillance program to assign species and
      strain status in samples positive for Burkholderia cepacia complex (Bcc). We
      sought to evaluate a usefulness of Bcc-specific PCR in infection control and to
      map evolution of the outbreak. METHODS: Since 2001, 6109 respiratory samples from
      299 CF patients were examined not only by conventional culture, but also by PCR,
      detecting Bcc directly in sputum. RESULTS: Diagnosis of Bcc infection was
      established by culture in 54 patients already prior to 2001. As 39 more patients
      were diagnosed by culture and/or PCR during 2001-2010, this represented annual
      prevalence of 18.5%-28.9%. Twelve of 39 patients were culture negative at the
      time of their first PCR positivity. Although 2/3 of them became subsequently
      culture positive, the time delay in diagnostics of the infection by culture
      ranged from 1 to 22 months. New cases of Bcc infection were detected every year,
      however a dramatic drop was observed for the epidemic strain ST32. CONCLUSION: A
      likely factor contributing to the end of ST32 epidemic was segregation of Bcc
      infected patients that included also patients with no culture, but PCR
      positivity. The diagnostic PCR led to timely identification of cases with
      'culture-invisible' infection.

PMID- 22622027
TI  - Human ESC self-renewal promoting microRNAs induce epithelial-mesenchymal
      transition in hepatocytes by controlling the PTEN and TGFbeta tumor suppressor
      signaling pathways.
AB  - The self-renewal capacity ascribed to embryonic stem cells (ESC) is reminiscent
      of cancer cell proliferation, raising speculation that a common network of genes
      may regulate these traits. A search for general regulators of these traits
      yielded a set of microRNAs for which expression is highly enriched in human ESCs
      and liver cancer cells (HCC) but attenuated in differentiated quiescent
      hepatocytes. Here, we show that these microRNAs promote hESC self-renewal, as
      well as HCC proliferation, and when overexpressed in normally quiescent
      hepatocytes, induce proliferation and activate cancer signaling pathways.
      Proliferation in hepatocytes is mediated through translational repression of
      Pten, Tgfbr2, Klf11, and Cdkn1a, which collectively dysregulates the
      PI3K/AKT/mTOR and TGFbeta tumor suppressor signaling pathways. Furthermore,
      aberrant expression of these miRNAs is observed in human liver tumor tissues and
      induces epithelial-mesenchymal transition in hepatocytes. These findings suggest
      that microRNAs that are essential in normal development as promoters of ESC self
      renewal are frequently upregulated in human liver tumors and harbor neoplastic
      transformation potential when they escape silencing in quiescent human
      hepatocytes.

PMID- 22622028
TI  - Alpha-melanocyte-stimulating hormone suppresses oxidative stress through a p53
      mediated signaling pathway in human melanocytes.
AB  - Epidermal melanocytes are skin cells specialized in melanin production.
      Activation of the melanocortin 1 receptor (MC1R) on melanocytes by alpha
      melanocyte-stimulating hormone (alpha-MSH) induces synthesis of the brown/black
      pigment eumelanin that confers photoprotection from solar UV radiation (UVR).
      Contrary to keratinocytes, melanocytes are slow proliferating cells that persist
      in the skin for decades, in an environment with high levels of UVR-induced
      reactive oxygen species (ROS). We previously reported that in addition to its
      role in pigmentation, alpha-MSH also reduces oxidative stress and enhances the
      repair of DNA photoproducts in melanocytes, independent of melanin synthesis.
      Given the significance of ROS in carcinogenesis, here we investigated the
      mechanisms by which alpha-MSH exerts antioxidant effects in melanocytes. We show
      that activation of the MC1R by alpha-MSH contributes to phosphorylation of p53 on
      serine 15, a known requirement for stabilization and activation of p53, a major
      sensor of DNA damage. This effect is mediated by the cAMP/PKA pathway and by the
      activation of phosphoinositide 3-kinase (PI3K) ATR and DNA protein kinase (DNA
      PK). alpha-MSH increases the levels of 8-oxoguanine DNA glycosylase (OGG1) and
      apurinic apyrimidinic endonuclease 1 (APE-1/Ref-1), enzymes essential for base
      excision repair. Nutlin-3, an HDM2 inhibitor, mimicked the effects of alpha-MSH
      resulting in reduced phosphorylation of H2AX (gamma-H2AX), a marker of DNA
      damage. Conversely, the p53 inhibitor pifithrin-alpha or silencing of p53
      abolished the effects of alpha-MSH and augmented oxidative stress. These results
      show that p53 is an important target of the downstream MC1R signaling that
      reduces oxidative stress and possibly malignant transformation of melanocytes.

PMID- 22622029
TI  - Sensing pressure with ion channels.
AB  - Opening of stretch-activated ion channels (SACs) is the earliest event occurring
      in mechanosensory transduction. The molecular identity of mammalian SACs has long
      remained a mystery. Only very recently, Piezo1 and Piezo2 have been shown to be
      essential components of distinct SACs and moreover, purified Piezo1 forms
      cationic channels when reconstituted into artificial bilayers. In line with these
      findings, dPiezo was demonstrated to act in the Drosophila mechanical nociception
      pathway. Finally, the 3D structure of the two-pore domain potassium channel
      (K(2P)), TRAAK [weakly inward rectifying K+ channel (TWIK)-related arachidonic
      acid stimulated K+ channel], has recently been solved, providing valuable
      information about pharmacology, selectivity and gating mechanisms of stretch
      activated K+ channels (SAKs). These recent findings allow a better understanding
      of the molecular basis of molecular and cellular mechanotransduction.

PMID- 22622031
TI  - Detection of nodular pulmonary amyloid by PET positive scan--deception for lung
      cancer.
AB  - Amyloidosis results from proteins being deposited as insoluble beta-pleated
      sheets and disrupting organ function. Each precursor protein induces a separate
      spectrum of organ involvement, and different disease manifestations within the
      lung. Although autopsy findings often demonstrate amyloid deposits in various
      compartments of the lung, few are manifested pathologically. Amyloid lung nodules
      with positron emission tomography (PET) uptake are rare. We describe a rare case
      where PET uptake was detected in a pulmonary amyloid nodule. To our knowledge
      there are six previously reported cases in the English literature. This review
      also focuses on amyloid derived from immunoglobulin light-chain protein (AL
      disease), which most frequently involves the lung in both systemic and localized
      forms of the disease. Manifestations of AL-related lung disease range from
      nodules identified on incidental chest films to diffuse alveolar and septal
      deposition mimicking malignancy and or diffuse alveolar damage.

PMID- 22622030
TI  - The thrifty lipids: endocannabinoids and the neural control of energy
      conservation.
AB  - The 'thrifty gene hypothesis' posits that evolution preferentially selects
      physiological mechanisms that optimize energy storage to increase survival under
      alternating conditions of abundance and scarcity of food. Recent experiments
      suggest that endocannabinoids - a class of lipid-derived mediators that activate
      cannabinoid receptors in many cells of the body - are key agents of energy
      conservation. The new evidence indicates that these compounds increase energy
      intake and decrease energy expenditure by controlling the activity of peripheral
      and central neural pathways involved in the sensing and hedonic processing of
      sweet and fatty foods, as well as in the storage of their energy content for
      future use.

PMID- 22622032
TI  - Structural genomics plucks high-hanging membrane proteins.
AB  - Recent years have seen the establishment of structural genomics centers that
      explicitly target integral membrane proteins. Here, we review the advances in
      targeting these extremely high-hanging fruits of structural biology in high
      throughput mode. We observe that the experimental determination of high
      resolution structures of integral membrane proteins is increasingly successful
      both in terms of getting structures and of covering important protein families,
      for example, from Pfam. Structural genomics has begun to contribute significantly
      toward this progress. An important component of this contribution is the set up
      of robotic pipelines that generate a wealth of experimental data for membrane
      proteins. We argue that prediction methods for the identification of membrane
      regions and for the comparison of membrane proteins largely suffice to meet the
      challenges of target selection for structural genomics of membrane proteins. In
      contrast, we need better methods to prioritize the most promising members in a
      family of closely related proteins and to annotate protein function from sequence
      and structure in absence of homology.

PMID- 22622033
TI  - Getting to the finish line with mTORC1-targeted therapy.
AB  - The mammalian target of rapamycin (mTOR) pathway is activated in the majority of
      human malignancies and thus seems a likely therapeutic target. However, this
      pathway is genetically complex, complicating studies using pharmacologic mTOR
      inhibitors. In this issue of the JCI, Hoshii et al. examined mice deficient in
      one of the mTOR effector complex proteins, Raptor, to elucidate the role of
      mTORC1 in leukemia. They convincingly demonstrate that Raptor deficiency, with
      consequent mTORC1 inhibition, blocks differentiation of leukemia cells and
      prolongs survival, but also allows a population of leukemia-initiating cells to
      persist in what appears to be a state of dormancy. Translating this new
      understanding into effective therapeutic strategies will require further study of
      the molecular mechanisms that underlie these processes.

PMID- 22622034
TI  - Restoring balance to B cells in ADA deficiency.
AB  - It is paradoxical that immunodeficiency disorders are associated with
      autoimmunity. Adenosine deaminase (ADA) deficiency, a cause of X-linked severe
      combined immunodeficiency (SCID), is a case in point. In this issue of the JCI,
      Sauer and colleagues investigate the B cell defects in ADA-deficient patients.
      They demonstrate that ADA patients receiving enzyme replacement therapy had B
      cell tolerance checkpoint defects. Remarkably, gene therapy with a retrovirus
      that expresses ADA resulted in the apparent correction of these defects, with
      normalization of peripheral B cell autoantibody frequencies. In vitro, agents
      that either block ADA or overexpress adenosine resulted in altered B cell
      receptor and TLR signaling. Collectively, these data implicate a B cell-intrinsic
      mechanism for alterations in B cell tolerance in the setting of partial ADA
      deficiency that is corrected by gene therapy.

PMID- 22622035
TI  - Taming endothelial activation with a microRNA.
AB  - Inflammation plays an essential role in vascular pathologies, including those
      associated with sepsis and atherosclerosis. Identifying negative regulators of
      inflammatory signaling pathways may provide novel therapeutic targets for these
      diseases. In this issue of the JCI, Sun et al. show that in endothelial cells,
      microRNA-18 1b (miR-18 1b) plays a vital role in controlling inflammation by
      targeting importin-alpha3, a regulator of NF-kappaB nuclear import. These
      findings provide compelling evidence that modulation of microRNAs may be a useful
      therapeutic approach for inflammatory vascular diseases.

PMID- 22622036
TI  - Blood flow reprograms lymphatic vessels to blood vessels.
AB  - Human vascular malformations cause disease as a result of changes in blood flow
      and vascular hemodynamic forces. Although the genetic mutations that underlie the
      formation of many human vascular malformations are known, the extent to which
      abnormal blood flow can subsequently influence the vascular genetic program and
      natural history is not. Loss of the SH2 domain-containing leukocyte protein of 76
      kDa (SLP76) resulted in a vascular malformation that directed blood flow through
      mesenteric lymphatic vessels after birth in mice. Mesenteric vessels in the
      position of the congenital lymphatic in mature Slp76-null mice lacked lymphatic
      identity and expressed a marker of blood vessel identity. Genetic lineage tracing
      demonstrated that this change in vessel identity was the result of lymphatic
      endothelial cell reprogramming rather than replacement by blood endothelial
      cells. Exposure of lymphatic vessels to blood in the absence of significant flow
      did not alter vessel identity in vivo, but lymphatic endothelial cells exposed to
      similar levels of shear stress ex vivo rapidly lost expression of PROX1, a
      lymphatic fate-specifying transcription factor. These findings reveal that blood
      flow can convert lymphatic vessels to blood vessels, demonstrating that
      hemodynamic forces may reprogram endothelial and vessel identity in
      cardiovascular diseases associated with abnormal flow.

PMID- 22622037
TI  - Transient telomere dysfunction induces chromosomal instability and promotes
      carcinogenesis.
AB  - Telomere shortening limits the proliferative capacity of a cell, but perhaps
      surprisingly, shortening is also known to be associated with increased rates of
      tumor initiation. A current hypothesis suggests that telomere dysfunction
      increases tumor initiation by induction of chromosomal instability, but that
      initiated tumors need to reactivate telomerase for genome stabilization and tumor
      progression. This concept has not been tested in vivo, since appropriate mouse
      models were lacking. Here, we analyzed hepatocarcinogenesis in a mouse model of
      inducible telomere dysfunction on a telomerase-proficient background, in
      telomerase knockout mice with chronic telomere dysfunction (G3 mTerc-/-), and in
      WT mice with functional telomeres and telomerase. Transient or chronic telomere
      dysfunction enhanced the rates of chromosomal aberrations during
      hepatocarcinogenesis, but only telomerase-proficient mice exhibited significantly
      increased rates of macroscopic tumor formation in response to telomere
      dysfunction. In contrast, telomere dysfunction resulted in pronounced
      accumulation of DNA damage, cell-cycle arrest, and apoptosis in telomerase
      deficient liver tumors. Together, these data provide in vivo evidence that
      transient telomere dysfunction during early or late stages of tumorigenesis
      promotes chromosomal instability and carcinogenesis in telomerase-proficient
      mice.

PMID- 22622038
TI  - Defective B cell tolerance in adenosine deaminase deficiency is corrected by gene
      therapy.
AB  - Adenosine deaminase (ADA) gene defects are among the most common causes of SCID.
      Restoration of purine metabolism and immune functions can be achieved by enzyme
      replacement therapy, or more effectively by bone marrow transplant or HSC gene
      therapy (HSC-GT). However, autoimmune complications and autoantibody production,
      including anti-nuclear antibodies (ANAs), frequently occur in ADA-SCID patients
      after treatment. To assess whether ADA deficiency affects the establishment of B
      cell tolerance, we tested the reactivity of recombinant antibodies isolated from
      single B cells of ADA-SCID patients before and after HSC-GT. We found that before
      HSC-GT, new emigrant/transitional and mature naive B cells from ADA-SCID patients
      contained more autoreactive and ANA-expressing clones, indicative of defective
      central and peripheral B cell tolerance checkpoints. We further observed impaired
      B cell receptor (BCR) and TLR functions in B cells after ADA inhibition, which
      may underlie the defects in B cell tolerance. Strikingly, after HSC-GT, ADA-SCID
      patients displayed quasi-normal early B cell tolerance checkpoints, as evidenced
      by restored removal of developing autoreactive and ANA-expressing B cells. Hence,
      ADA plays an essential role in controlling autoreactive B cell counterselection
      by regulating BCR and TLR functions.

PMID- 22622039
TI  - A stapled BIM peptide overcomes apoptotic resistance in hematologic cancers.
AB  - Cancer cells subvert the natural balance between cellular life and death,
      achieving immortality through pathologic enforcement of survival pathways and
      blockade of cell death mechanisms. Pro-apoptotic BCL-2 family proteins are
      frequently disarmed in relapsed and refractory cancer through genetic deletion or
      interaction-based neutralization by overexpressed antiapoptotic proteins,
      resulting in resistance to chemotherapy and radiation treatments. New
      pharmacologic strategies are urgently needed to overcome these formidable
      apoptotic blockades. We harnessed the natural killing activity of BCL-2
      interacting mediator of cell death (BIM), which contains one of the most potent
      BH3 death domains of the BCL-2 protein family, to restore BH3-dependent cell
      death in resistant hematologic cancers. A hydrocarbon-stapled peptide modeled
      after the BIM BH3 helix broadly targeted BCL-2 family proteins with high
      affinity, blocked inhibitory antiapoptotic interactions, directly triggered
      proapoptotic activity, and induced dose-responsive and BH3 sequence-specific cell
      death of hematologic cancer cells. The therapeutic potential of stapled BIM BH3
      was highlighted by the selective activation of cell death in the aberrant
      lymphoid infiltrates of mice reconstituted with BIM-deficient bone marrow and in
      a human AML xenograft model. Thus, we found that broad and multimodal targeting
      of the BCL-2 family pathway can overcome pathologic barriers to cell death.

PMID- 22622040
TI  - MicroRNA-181b regulates NF-kappaB-mediated vascular inflammation.
AB  - EC activation and dysfunction have been linked to a variety of vascular
      inflammatory disease states. The function of microRNAs (miRNAs) in vascular EC
      activation and inflammation remains poorly understood. Herein, we report that
      microRNA-181b (miR-181b) serves as a potent regulator of downstream NF-kappaB
      signaling in the vascular endothelium by targeting importin-alpha3, a protein
      that is required for nuclear translocation of NF-kappaB. Overexpression of miR
      181b inhibited importin-alpha3 expression and an enriched set of NF-kappaB
      responsive genes such as adhesion molecules VCAM-1 and E-selectin in ECs in vitro
      and in vivo. In addition, treatment of mice with proinflammatory stimuli reduced
      miR-181b expression. Rescue of miR-181b levels by systemic administration of miR
      181b "mimics" reduced downstream NF-kappaB signaling and leukocyte influx in the
      vascular endothelium and decreased lung injury and mortality in endotoxemic mice.
      In contrast, miR-181b inhibition exacerbated endotoxin-induced NF-kappaB
      activity, leukocyte influx, and lung injury. Finally, we observed that critically
      ill patients with sepsis had reduced levels of miR-181b compared with control
      intensive care unit (ICU) subjects. Collectively, these findings demonstrate that
      miR-181b regulates NF-kappaB-mediated EC activation and vascular inflammation in
      response to proinflammatory stimuli and that rescue of miR-181b expression could
      provide a new target for antiinflammatory therapy and critical illness.

PMID- 22622041
TI  - mTORC1 is essential for leukemia propagation but not stem cell self-renewal.
AB  - Although dysregulation of mTOR complex 1 (mTORC1) promotes leukemogenesis, how
      mTORC1 affects established leukemia is unclear. We investigated the role of
      mTORC1 in mouse hematopoiesis using a mouse model of conditional deletion of
      Raptor, an essential component of mTORC1. Raptor deficiency impaired granulocyte
      and B cell development but did not alter survival or proliferation of
      hematopoietic progenitor cells. In a mouse model of acute myeloid leukemia (AML),
      Raptor deficiency significantly suppressed leukemia progression by causing
      apoptosis of differentiated, but not undifferentiated, leukemia cells. mTORC1 did
      not control cell cycle or cell growth in undifferentiated AML cells in vivo.
      Transplantation of Raptor-deficient undifferentiated AML cells in a limiting
      dilution revealed that mTORC1 is essential for leukemia initiation. Strikingly, a
      subset of AML cells with undifferentiated phenotypes survived long-term in the
      absence of mTORC1 activity. We further demonstrated that the reactivation of
      mTORC1 in those cells restored their leukemia-initiating capacity. Thus, AML
      cells lacking mTORC1 activity can self-renew as AML stem cells. Our findings
      provide mechanistic insight into how residual tumor cells circumvent anticancer
      therapies and drive tumor recurrence.

PMID- 22622042
TI  - Identification of a novel pneumococcal vaccine antigen preferentially expressed
      during meningitis in mice.
AB  - Streptococcus pneumoniae is the most common cause of severe bacterial meningitis
      in children, the elderly, and immunocompromised individuals. To identify
      virulence factors preferentially expressed during meningitis, we conducted niche
      specific genome-wide in vivo transcriptomic analysis after intranasal infection
      of mice with serotype 4 or 6A pneumococci. The expression of 34 bacterial genes
      was substantially altered in brain tissue of mice infected with either of the 2
      strains. Ten upregulated genes were common to both strains, 7 of which were
      evaluated for their role in the development of meningitis. One previously
      uncharacterized protein, alpha-glycerophosphate oxidase (GlpO), was cytotoxic for
      human brain microvascular endothelial cells (HBMECs) via generation of H(2)O(2).
      A glpO deletion mutant was defective in adherence to HBMECs in vitro as well as
      in progression from the blood to the brain in vivo. Mutant bacteria also induced
      markedly reduced meningeal inflammation and brain pathology compared with wild
      type, despite similar levels of bacteremia. Immunization of mice with GlpO
      protected against invasive pneumococcal disease and provided additive protection
      when formulated with pneumolysin toxoid. Our results provide the basis of a
      strategy that can be adapted to identify genes that contribute to the development
      of meningitis caused by other pathogens.

PMID- 22622043
TI  - Therapeutic potential of a peptide targeting BCL-2 cell guardians in cancer.
AB  - A promising approach to cancer therapy is to elicit apoptosis with "BH3 mimetic"
      drugs, which target proteins of the BCL-2 family. As of yet, however, such drugs
      can target only certain BCL-2 family proteins. Hence, in this issue of the JCI,
      LaBelle et al. assess instead the therapeutic potential of a "stapled" BH3
      peptide from the BIM protein, which inactivates all its prosurvival relatives.
      The peptide killed cultured hematologic tumor cells and abated growth of a
      leukemia xenograft, without perturbing the hematopoietic compartment. Hence, such
      peptides might eventually provide a new way to treat refractory leukemias.

PMID- 22622044
TI  - Telomere stability and carcinogenesis: an off-again, on-again relationship.
AB  - Previous studies in mice have demonstrated antagonistic effects of telomerase
      loss on carcinogenesis. Telomere attrition can promote genome instability,
      thereby stimulating initiation of early-stage cancers, but can also inhibit
      tumorigenesis by promoting permanent cell growth arrest or death. Human cancers
      likely develop in cell lineages with low levels of telomerase, leading to
      telomere losses in early lesions, followed by subsequent activation of
      telomerase. Mouse models constitutively lacking telomerase have thus not
      addressed how telomere losses within telomerase-proficient cells have an impact
      on carcinogenesis. Using a novel transgenic mouse model, Begus-Nahrmann et al.
      demonstrate in this issue of the JCI that transient telomere dysfunction in
      telomerase-proficient animals is a potent stimulus of tumor formation.

PMID- 22622045
TI  - Emergence of heterogeneous nuclear ribonucleoprotein A2/B1 vs loss of E-cadherin:
      their reciprocal immunoexpression profiles in human pancreatic cancer.
AB  - Pancreatic cancer is one of the most lethal human cancers worldwide. It is
      important to develop new screening methods or biomarkers related to pancreatic
      carcinogenesis. In our previous work, we identified heterogeneous nuclear
      ribonucleoprotein (hnRNP) A2/B1 as one of the up-regulated proteins in rat
      pancreatic cancer by using proteomic analysis. In the current study, we extended
      our research to investigate the immunoexpression of hnRNP A2/B1 protein in paired
      tumor/nontumor tissues from 42 patients with primary pancreatic ductal
      adenocarcinoma and its correlation to E-cadherin expression and clinicopathologic
      features. The results showed that the frequency of hnRNP A2/B1 expression is
      71.4% (30/42), and loss of E-cadherin is 61.9% (26/42) in pancreatic cancer
      tissue. Emergence of hnRNP A2/B1 (P = .027) and loss of E-cadherin (P = .012)
      expression were significantly associated with poor differentiation of pancreatic
      cancer. In addition, E-cadherin loss expression was associated with lymph node
      metastasis (P = .042). Most importantly, there was an inverse correlation between
      the emergence of hnRNP A2/B1 and loss of E-cadherin expression in pancreatic
      cancer (P = .01). Collectively, we demonstrate altered expression profile of
      hnRNP A2/B1 protein in human pancreatic cancer and its reciprocal correlation to
      E-cadherin expression. These data indicate that hnRNP A2/B1 overexpression is
      novel and requires further investigation for its potential application in
      pancreatic carcinogenesis.

PMID- 22622047
TI  - Accelerating cancer evolution: a dark side of SIRT1 in genome maintenance.

PMID- 22622048
TI  - Molecular pathogenesis of malignant mesothelioma.
AB  - Malignant mesothelioma is a rare, highly aggressive cancer arising from
      mesothelial cells that line the pleural cavities. Approximately 80% of
      mesothelioma cases can be directly attributed to asbestos exposure. Additional
      suspected causes or co-carcinogens include other mineral fibres, simian virus 40
      (SV40) and radiation. A mesothelioma epidemic in Turkey has demonstrated a
      probable genetic predisposition to mineral fibre carcinogenesis and studies of
      human tissues and animal models of mesothelioma have demonstrated genetic and
      epigenetic events that contribute to the multistep process of mineral fibre
      carcinogenesis. Several growth factors and their receptors have a significant
      role in the oncogenesis, progression and resistance to therapy of mesothelioma.
      Epidermal growth factor (EGF), hepatocyte growth factor (HGF), vascular
      endothelial growth factor (VEGF) and insulin-like growth factor (IGF) have been
      shown as targets for therapy based on promising preclinical data. However,
      clinical trials of tyrosine kinase inhibitors in mesothelioma have been
      disappointing. Bcl-XL is an important antiapoptotic member of the Bcl-2 family
      and is overexpressed in several solid tumours, including mesothelioma. Reduction
      of Bcl-XL expression in mesothelioma induces apoptosis and engenders
      sensitisation to cytotoxic chemotherapeutic agents. Pharmacological inhibitors of
      antiapoptotic Bcl-2 family members continue to undergo refinement and have shown
      promise in mesothelioma.

PMID- 22622050
TI  - Efficacy of immediate and delayed cognitive and physical rest for treatment of
      sports-related concussion.
AB  - OBJECTIVES: To evaluate the efficacy of cognitive and physical rest for the
      treatment of concussion. STUDY DESIGN: High school and collegiate athletes (N =
      49) underwent post-concussion evaluations between April 2010 and September 2011
      and were prescribed at least 1 week of cognitive and physical rest. Participants
      were assigned to groups on the basis of the time elapsed between sustaining a
      concussion and the onset of rest (1-7 days, 8-30 days, 31+ days). Main outcome
      measures included Concussion Symptom Scale ratings and scores on the 4 composite
      indices of the Immediate Post-Concussion Assessment and Cognitive Testing
      measure, both before and following rest. Mixed-factorial design ANOVA were used
      to compare changes on the dependent measures within and between groups. RESULTS:
      Participants showed significantly improved performance on Immediate Post
      Concussion Assessment and Cognitive Testing and decreased symptom reporting
      following prescribed cognitive and physical rest (P < .001), regardless of the
      time between concussion and onset of rest (P = .44). CONCLUSION: These
      preliminary data suggest that a period of cognitive and physical rest may be a
      useful means of treating concussion-related symptoms, whether applied soon after
      a concussion or weeks to months later.

PMID- 22622051
TI  - Prediabetic obese adolescents have a more atherogenic lipoprotein profile
      compared with normoglycemic obese peers.
AB  - OBJECTIVE: To compare lipoprotein profiles of prediabetic to normoglycemic obese
      adolescents. STUDY DESIGN: Cross-sectional study of 95 obese, pubertal
      adolescents (12-17 years), who underwent oral glucose tolerance test, lipid
      panel, and lipoprotein subclass particle analysis (nuclear magnetic resonance
      spectroscopy). Univariate and linear regression analyses compared prediabetic and
      normoglycemic groups. RESULTS: Of 95 obese adolescents enrolled in the study,
      22.1% (n = 21) had prediabetes. They were similar to normoglycemic adolescents (n
      = 74) in age, race, body mass index, standard lipids, total low-density
      lipoprotein particles (LDL-P), and total high-density lipoprotein particles (HDL
      P). However, prediabetics had higher concentrations of small LDL-P (714.0 +/-
      288.0 vs 537.7 +/- 266.5 nmol/L, P = .01) and smaller LDL-P size (20.73 +/- 0.41
      vs 21.18 +/- 0.65 nm, P = .003), than normoglycemic youth. Prediabetics had
      higher small HDL-P (18.5 +/- 3.8 vs 16.6 +/- 3.9 umol/L, P = .046), lower large
      HDL-P (4.49 +/- 2.0 vs 6.32 +/- 2.6 umol/L, P = .004), and smaller HDL-P size
      (8.73 +/- 0.31 vs 9.01 +/- 0.39 nm, P = .003). After adjusting for demographics,
      Tanner stage, and body mass index using multiple linear regression, all
      differences remained significant except for small HDL-P. After additional
      adjustment for Homeostasis Model Assessment-Insulin Resistance Index, only LDL-P
      size difference remained significant. CONCLUSION: Obese prediabetic adolescents
      have a significantly more atherogenic lipoprotein profile compared with obese
      normoglycemic peers. Prediabetic adolescents may benefit from more aggressive
      interventions to decrease future cardiovascular risk.

PMID- 22622052
TI  - Measurement accuracy of non-invasively obtained central blood pressure by
      applanation tonometry: a systematic review and meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: Non-invasive methods based on applanation tonometry
      have been proposed to estimate central blood pressure. However, the accuracy of
      these methods hasn't been systematically examined. METHODS: We performed a
      systematic review and meta-analysis of studies comparing estimated and invasively
      measured central BP. RESULTS: Sufficient data were available in 22 studies for
      meta-analysis (857 subjects and 1167 measurements). Acquired arterial pressure
      waveforms in these studies were directly measured, calibrated to match invasive
      aortic mean BP and diastolic BP or calibrated to match brachial BP measured with
      a sphygmomanometer, cuff BP. Of the former 2 conditions, the errors of estimated
      central BP were small with a mean and standard deviation of difference -1.1 +/-
      4.1mm Hg (95% limits of agreement -9.1-6.9 mm Hg) for central systolic BP; -0.5
      +/- 2.1mm Hg (-4.6-3.6mm Hg) for central diastolic BP; and -0.8 +/- 5.1mm Hg (
      10.8-9.2mm Hg) for central pulse pressure. However, the errors inflated to -8.2
      +/- 10.3mm Hg (-28.4-12.0mm Hg) for central systolic BP, 7.6 +/- 8.7 mm Hg (-9.5
      24.6mm Hg) for central diastolic BP, and -12.2 +/- 10.4mm Hg (-32.5-8.1mm Hg) for
      central pulse pressure, when calibrated to cuff BP. The findings were still
      evident in subgroup analysis conducted with different central BP estimating
      methods and validated cuff BP monitors. CONCLUSION: Present tonometry-based
      central BP estimating methods are acceptable in theory, with small errors.
      However, based on current available evidence, there is substantial room for
      improvement in measurement accuracy of central BP when cuff BP is used to
      calibrate the peripheral waveforms.

PMID- 22622049
TI  - Immunogenicity and safety of 1 vs 2 doses of quadrivalent meningococcal conjugate
      vaccine in youth infected with human immunodeficiency virus.
AB  - OBJECTIVE: To compare the immunogenicity of 1 vs 2 doses of meningococcal
      polysaccharide conjugate vaccine (MCV4) in youth infected with human
      immunodeficiency virus (HIV). STUDY DESIGN: P1065 was a phase I/II immunogenicity
      and safety trial of MCV4 in 324 youth infected with HIV performed at 27 sites of
      the International Maternal Pediatric Adolescent AIDS Clinical Trials Group
      network in the US. At entry subjects received 1 dose of MCV4. At 24 weeks, those
      with screening cluster of differentiation 4 (CD4)% >= 15 were randomized to
      receive a second dose or not, and all with screening CD4% <15 received a second
      dose. Immunogenicity was evaluated as the proportion of subjects with a >= 4-fold
      rise from entry in serum bactericidal antibody against each meningococcal
      serogroup (SG) at weeks 28 and 72. Logistic regression models adjusting for HIV
      disease severity were used to evaluate the effect of 1 vs 2 MCV4 doses among
      those with screening CD4% >= 15. RESULTS: Subjects randomized to receive 2 vs 1
      MCV4 dose had significantly higher response rates to all SGs at week 28 and to
      all except Neisseria meningitidis SG Y at week 72, with adjusted ORs of 2.5-5.6.
      In 31 subjects with screening CD4% <15 who received 2 MCV4 doses, response rates
      ranged from 22%-55% at week 28 and 6%-28% at week 72. CONCLUSION: In youth
      infected with HIV with a CD4% >= 15, a second dose of MCV4 given 6 months after
      the initial dose significantly improves response rates at 28 and 72 weeks.
      Subjects with CD4% <15 at entry had lower response rates despite 2 doses of MCV4.

PMID- 22622053
TI  - Infusion of lin-/sca-1+ and endothelial progenitor cells improves proinflammatory
      and oxidative stress markers in atherosclerotic mice.
AB  - BACKGROUND: The effects of direct infusion or indirect mobilization of progenitor
      cells on atherosclerotic plaque development and progression are not clear. We
      sought to investigate the effects of hematopoietic progenitors lineage
      negative/stem cell antigen-1 positive (lin-/sca-1+) cells, endothelial progenitor
      cells and G-CSF administration on the inflammatory and oxidative component of
      atherosclerosis. METHODS: Splenectomized ApoE(-/-) C57BL/6J mice (6-8 weeks of
      age) fed with a high-fat, cholesterol-rich diet for 6 weeks, were divided in four
      groups (n=10/group) and received two intravenous injections of 5 * 10(5) cells
      (lin-/sca-1+ or EPCs), or granulocyte colony-stimulating factor (G-CSF 100
      MUg/kg/day) for 7 days or normal saline. sVCAM-1 (Vascular cell adhesion protein
      1), sICAM-1 (soluble intercellular adhesion molecule-1), sE-Selectin,
      Metalloproteinase 9 (MMP-9), Plasminogen activator inhibitor (PAI-1), Interleukin
      6 (IL-6), oxidized LDL (ox-LDL) levels and lipid PEROX were evaluated at the day
      of the first infusion, 7 days later and 6 weeks post-treatment with ELISA.
      RESULTS: The administration of both G-CSF and progenitor cells significantly
      decreased the levels of sICAM-1, sVCAM-1,sE-Selectin, IL-6, ox-LDL and lipid
      Perox 6 weeks after the initiation of treatment. No significant effects of lin
      /sca-1+ cells, EPCs and G-CSF on PAI-1 and MMP-9 levels were observed. The
      effects of all treatments on the levels of pro-inflammatory molecules and
      oxidative stress parameters 7 days post-treatment were not significant.
      Interestingly, the levels of sICAM-1and sE-selectin were increased 7 days post
      treatment. CONCLUSIONS: Direct infusion of progenitor cells and indirect
      mobilization of hematopoietic progenitor cells significantly decreased the levels
      of proinflammatory molecules and oxidative stress parameters in a murine model of
      atherosclerosis. The principal novelty of this work is that treatment with
      hematopoietic progenitors, EPCs or G-CSF may exert beneficial effects on vascular
      inflammation and atherosclerotic plaque development.

PMID- 22622054
TI  - Cardiovascular system and endogenous subclinical hyperthyroidism treatment: the
      time has come.

PMID- 22622055
TI  - A 22-year old female with cardiogenic shock due to transplant vasculopathy with
      severe left main stenosis.

PMID- 22622056
TI  - Disturbed carnitine regulation in chronic heart failure--increased plasma levels
      of palmitoyl-carnitine are associated with poor prognosis.
AB  - BACKGROUND/OBJECTIVES: Heart failure is characterized by disturbed energy
      metabolism and impaired mitochondrial function. L-carnitine plays a critical role
      in fatty acid transport into the mitochondria and may thus influence inflammation
      and myocardial function. The aim of this study was to investigate carnitine
      metabolism in relation to progression of heart failure (HF). METHODS AND RESULTS:
      We examined plasma levels of free L-carnitine as well as several of its
      precursors and derivates in HF patients (n=183) and matched healthy controls
      (n=111) as well as their relationship with cardiac dysfunction as assessed by
      echocardiographic measurements, inflammation (CRP) and neurohormonal activation
      (NT-proBNP) in addition to the prognostic value of carnitine derivates in
      relation to mortality in these patients. High levels of the carnitine derivates
      acetyl-carnitine and in particular palmitoyl-carnitine were associated with the
      degree of HF as evaluated by clinical (NYHA functional class) and neurohormonal
      assessments. Moreover, plasma levels of palmitoyl-carnitine were associated with
      serious adverse events (i.e., all-cause mortality and heart transplantation)
      during follow-up, independently of more established risk markers such as CRP and
      NT-proBNP, when analyzed by cox-regression and continous net reclassification
      improvement, but not c-statistics. CONCLUSIONS: Our findings support a role for
      disturbed carnitine metabolism in the pathogenesis of HF, and suggest that some
      of its derivates could give prognostic information in these patients.

PMID- 22622057
TI  - Role of routine early angiography post-fibrinolysis for ST elevation myocardial
      infarction--a meta-regression analysis using angiography rate in the non-routine
      arm.
AB  - BACKGROUND: The current European and American Guidelines differ with regard to
      the recommended level for the use of routine early angiography after fibrinolysis
      for STEMI. Previous meta-analyses on randomized controlled trials have supported
      the routine early approach, but its advantage may be because of an excessively
      low angiography rate among patients in the non-routine strategy arm of the
      trials. METHODS: We update the meta-analysis and apply meta-regression to
      evaluate whether the difference in outcome between the 2 randomized arms could be
      explained by the angiography rates in the non-routine strategy arm. Because
      reinfarction and recurrent ischemia are often the reported indication for
      angiography, we only use mortality endpoint in our meta-regression analysis.
      RESULTS: Among the eight trials included with 3195 patients, the angiography rate
      in the non-routine strategy arms ranges from 15% to 100%. The overall odds ratio
      for 30-day mortality comparing the routine early angiography arm vs the non
      routine arm is 0.86 (95% confidence interval 0.60-1.24). On the plot listing the
      eight trials according to angiography rates, there is no visual trend in the odds
      ratio estimates for mortality when comparing the 2 treatment strategies as
      angiography rate decreases. In meta-regression analysis, angiography rate does
      not predict 30-day mortality (p=0.461). CONCLUSION: For STEMI, mortality endpoint
      trumps the softer endpoints of recurrent infarction and ischemia. The current
      study shows that the equipoise between the routine early invasive versus the non
      routine strategy on 30-day mortality cannot be explained by the variable
      performance of angiography in the non-routine strategy arm.

PMID- 22622058
TI  - Cardiopulmonary and endothelial effects of metformin treatment in an insulin
      resistant population.

PMID- 22622059
TI  - Planning left atrial appendage occlusion using cardiac multidetector computed
      tomography.

PMID- 22622060
TI  - Novel polymer anchored Cr(III) Schiff base complexes: synthesis, characterization
      and antimicrobial properties.
AB  - New polymer-bound Schiff bases and Cr(III) complexes have been synthesized by the
      reaction of 4-benzyloxybenzaldehyde, polymer-bound with 2-aminophenol, 2-amino-4
      chlorophenol and 2-amino-4-methylphenol. The structure of polymeric-Schiff bases
      and their Cr(III) complexes have been characterized by elemental analyses,
      magnetic measurements, IR, UV-Vis, TG-DTA and (1)H-NMR. All these compounds have
      also been investigated for antibacterial activity by the well-diffusion method
      against Staphylococcus aureus (RSKK-07035), Shigella dysenteria type 10 (RSKK
      1036), Listeria monocytogenes 4b(ATCC 19115, Escherichia coli (ATCC 1230),
      Salmonella typhi H (NCTC 901.8394), Staphylococcus epidermis (ATCC 12228),
      Brucella abortus (RSKK-03026), Micrococcs luteus (ATCC 93419, Bacillus cereus
      sp., Pseudomonas putida sp. and for antifungal activity against Candida albicans
      (Y-1200-NIH).

PMID- 22622061
TI  - Tertiary lymphoid organs in infection and autoimmunity.
AB  - The lymph nodes (LNs) and spleen have an optimal structure that allows the
      interaction between T cells, B cells and antigen-presenting dendritic cells (DCs)
      on a matrix made up by stromal cells. Such a highly organized structure can also
      be formed in tertiary lymphoid organs (TLOs) at sites of infection or chronic
      immune stimulation. This review focuses on the molecular mechanisms of TLO
      formation and maintenance, the controversies surrounding the nature of the
      inducing events, and the functions of these structures in infection,
      transplantation and autoimmunity.

PMID- 22622062
TI  - An LC-MS/MS method for determination of jujuboside A in rat plasma and its
      application to pharmacokinetic studies.
AB  - A novel, simple, and sensitive method for the determination of jujuboside A in
      rat plasma using liquid chromatography coupled to tandem mass spectrometry (LC
      MS/MS) was developed. Following solid-phase extraction, measurement of jujuboside
      A was performed by negative ion electrospray ionization (ESI) in multiple
      reaction monitoring (MRM) mode. The limit of detection was 1.25 ng/mL, and the
      lower limit of quantification was 5 ng/mL in rat plasma. Good linearity was
      obtained over the range of 6.25-500 ng/mL, and the correlation coefficient was
      better than 0.998. The intra- and inter-day precisions ranged 4.4-7.5% and 2.9
      10.7%, respectively. The accuracy derived from QC samples ranged 3.2-7.8% and 2.2
      3.5%, respectively. The recovery ranged from 72.9 to 75.1% and the matrix effect
      from 96.7 to 105.3%. The analyte was stable under various conditions (at room
      temperature, during freeze-thaw, in the autosampler and under deep-freeze
      conditions). The developed method was successfully applied to the pharmacokinetic
      study in rats.

PMID- 22622063
TI  - Simple, cheap and effective high-performance liquid chromatographic method for
      determination of praziquantel in bovine muscle.
AB  - A simple high-performance liquid chromatographic method using ultraviolet
      detection was developed for the determination of praziquantel in bovine muscle.
      The sample was extracted with ethyl acetate, cleaned up by alumin B cartridge.
      Analyses were run at a flow-rate of 0.8 ml/min with the detector operating at a
      detection wavelength of 220 nm. The method is specific and sensitive, with a
      quantification limit of 0.02 mg/kg and a detection limit of 0.01 mg/kg. The
      standard calibration curve of drugs solution was linear in the range of 0.02-2.0
      MUg/ml (r2 = 0.9999). At the fortified levels of 0.02, 0.05, 0.2 mg/kg, the mean
      recoveries of praziquantel ranged from 75% to 85%, while the intra-day and inter
      day coefficient of variation (CV) of the assay were all less than 9%.

PMID- 22622064
TI  - Low-density solvent-based dispersive liquid-liquid microextraction followed by
      high performance liquid chromatography for determination of warfarin in human
      plasma.
AB  - Extraction and determination of warfarin, a widely used anticoagulant drug, in
      human plasma were performed using a new generation of dispersive liquid-liquid
      microextraction (DLLME) and high performance liquid chromatography (HPLC). The
      extraction procedure is based on extraction solvents lighter than water and
      performing of extraction in a specially designed extraction cell. Some important
      parameters, including kind and volume of extraction and disperser solvents, pH of
      the sample solution, salt concentration in the sample solution and extraction
      time were investigated and optimized. Under the optimized conditions (150 MUL 1
      octanol as extraction solvent, 150 MUL methanol as disperser solvent,
      pH(sample)=2.3, extraction time of 2 min, without salt addition), limit of
      detection (LOD) of 5 ng mL-1 and extraction recovery of 91.0% were obtained. The
      calibration curve was linear within the range of 15-3000 ng mL-1 with the square
      of correlation coefficient (R2) of 0.998. Repeatability and reproducibility of
      method based on five replicate extraction and determination were 2.8% and 6.5%,
      respectively. The proposed method was applied successfully for the determination
      of warfarin in plasma sample from a patient under treatment with this drug, and
      was demonstrated to be sensitive, efficient, and convenient.

PMID- 22622065
TI  - An improved high performance liquid chromatography-diode array detection-mass
      spectrometry method for determination of carotenoids and their precursors
      phytoene and phytofluene in human serum.
AB  - An improved high performance liquid chromatography-diode array detection-mass
      spectrometry method was developed for determination of various carotenoids and
      their precursors phytoene and phytofluene in human serum. A polymeric C30 column
      and mobile phase of (A) methanol/acetonitrile/water (84:14:4, v/v/v) and (B)
      dichloromethane (100%) were employed with the gradient condition of 100% A and 0%
      B initially, raised to 10% B at 4 min, 18% B at 12 min, 21% B at 17 min, 30% B at
      20 min and maintained until 25 min and increased further to 39% B at 28 min, 60%
      B at 40 min and returned to 100% A and 0% B at 45 min. A total of 30 carotenoids,
      including 6 all-trans forms, 20 cis-isomers, 2 beta-carotene epoxides, phytoene
      and phytofluene, were resolved within 45 min at a flow-rate of 1 mL/min, column
      temperature 25  degrees C and detection wavelengths 450, 348 and 286 nm.
      Identification of carotenoids was carried out by comparing retention behavior,
      absorption and mass spectral data with those of reference standards, isomerized
      standards and reported values. An internal standard parared was found appropriate
      for quantitation of all the carotenoids. The developed method provided high
      sensitivity with low detection and quantitation limits (2-14 and 6-43 ng/mL),
      high recovery (91-99%), and small intra-day and inter-day variations (0.14-6.01%
      and 0.31-7.28%). Application of the developed method to Taiwan subjects
      supplemented with carotenoid-rich capsules revealed beta-carotene plus its cis
      isomers as well as epoxide derivatives to be present in largest amount (1069.8
      2783.1 ng/mL) in serum, followed by lutein plus its cis isomers (511.6-2009.5
      ng/mL), phytofluene plus its cis isomer (515.0-1765.0 ng/mL), lycopene plus its
      cis isomers (551.1-1455.1 ng/mL), beta-cryptoxanthin plus its cis isomers (458.0
      965.0 ng/mL), all-trans-zeaxanthin (110.0-177.0 ng/mL), phytoene (41.8-165.0
      ng/mL) and all-trans-alpha-carotene (37.5-95.9 ng/mL).

PMID- 22622067
TI  - [Staged oesophageal reconstruction for benign disease].
AB  - OBJECTIVES: To assess morbidity, mortality and quality of life after oesophageal
      reconstruction in patients with oesophageal exclusion for benign diseases.
      PATIENTS AND METHODS: From 2002 to 2011, 20 of 24 patients with esophageal
      exclusion due to benign disease underwent a delayed reconstruction. We analyzed
      morbidity, mortality and health-related quality of life using the SF-36
      questionnaire, before and after reconstruction. RESULTS: Twenty patients were
      operated (16 men and 4 women) with an average age of 54.5 +/- 10.5 years. Main
      causes of oesophageal disconnection were: 10 cases of caustics ingestion, 3
      iatrogenic perforations, 4 anastomotic leaks and 3 cases with Boerhaave syndrome.
      Fourteen (60%) coloplasties and 6 (25%) gastric interpositions were performed
      with an average time of 212,2 +/- 23.5 days after oesophageal exclusion.
      Pulmonary complications were the most common postoperative complications (55%
      patients) and according to the modified Clavien classification were divided into:
      grade 1 (10%), grade 2 (15%), grade 3a (40%), grade 3b (10%), and grade 4a (10%).
      The 30-day mortality (grade 5) of the series was 10%. Quality of life after
      reconstruction improved significantly in all analyzed domains of the SF-36
      questionnaire. CONCLUSIONS: Deferred oesophageal reconstruction is associated
      with a high morbidity and a mortality rate of 10%. After reconstruction, the
      quality of life improved in all the parameters evaluated.

PMID- 22622066
TI  - Simultaneous determination of lercanidipine, benazepril and benazeprilat in
      plasma by LC-MS/MS and its application to a toxicokinetics study.
AB  - We aim to develop a rapid, simple, sensitive and specific LC-MS/MS method for the
      simultaneous quantification of lercanidipine, benazepril and benazeprilat in
      plasma. It is performed on the Agilent 6410 LC-MS/MS under the multiple-reaction
      monitoring (MRM) mode with electrospray ionization. Gliclazide was used as the
      internal standard (IS). Analytes and IS were extracted from plasma by solid-phase
      extraction. The reconstituted samples were chromatographed on a Diamond C18(150
      mm * 4.6 mm, 5 MUm) column. The mobile phase was composed of 0.1% acetic acid
      acetonitrile (50:50, v/v), with gradient flow rates: 0.6 mL/min (0-4.55 min);
      4.55-4.65 min, 1 mL/min; 1 mL/min (4.65-9.5 min); 9.5-9.6 min, 0.6 mL/min; 0.6
      mL/min (9.6-10 min). Method validation demonstrated that the method was of
      satisfactory specificity, sensitivity, precision and accuracy in linear ranges of
      1-2000 ng/mL for lercanidipine, 1-2000 ng/mL for benazepril and 1-1600 ng/mL for
      benazeprilat, respectively. The precision (RSD%) was better than 15, and the
      lower limit of quantitation was identifiable and reproducible at 1 ng/mL for the
      three analytes. The plasma samples were stable after being stored for more than
      60 days and after two freeze-thaw cycles (-20 to -25  degrees C). It is
      demonstrated that this method was successfully applied to samples from a
      toxicokinetics study of a compound of lercanidipine and benazepril in beagle
      dogs.

PMID- 22622068
TI  - [Primary hyperparathyroidism and acute toxic hypercalcaemic crisis].
AB  - OBJECTIVES: To describe the clinical characteristics and surgical treatment of
      patients with acute hypercalcaemia due to primary hyperparathyroidism (PHPT) and
      compare them with other patients with PHPT without associated acute
      hypercalcaemia. MATERIAL AND METHODS: A prospective, observational study (1998
      2010) was conducted on 158 patients with PHPT treated by parathyroidectomy. Those
      with acute hypercalcaemia (>14 mg/dl -3.5 mmol/L- or >3 mmol/L with symptoms of
      calcium toxicity) were evaluated by recording their clinical and treatment
      characteristics, and comparing them, using the Mann-Whitney U test and the Fisher
      test, with the 146 PHPT patients without hypercalcaemic crisis. RESULTS: Twelve
      patients (7.6%) had acute hypercalcaemia with symptoms of calcium toxicity and
      other symptoms of chronicity. The preoperative calcium and PTH values were 14.5
      +/- 1.3mg/dL and 648.2 +/- 542 pg/dL, respectively. There were 10 adenomas, 1
      hyperplasia and 1 carcinoma. The mean weight of the surgical pieces was 4.075 +/-
      2.918 mg, with a diameter greater than 27 +/- 14 mm. The gradients of PTH at 10
      and 25 minutes were 79 +/- 18% and 92 +/- 6%, respectively. Post-operative
      calcium values on discharge and at 6 months were 8.2 +/- 0.7 mg/dL and 9.1 +/-
      0.9 mg/dL, respectively. The plasma concentrations of calcium, PTH, and the size
      of the surgical pieces were higher in patients with hypercalcaemic crisis
      (P<0.001). There were no differences in the other parameters studied or in the
      cure rate. CONCLUSIONS: Hypercalcaemic crises were caused by larger and heavier
      tumours that led to higher plasma Ca and PTH plasma concentrations. All patients
      had long-standing symptoms and parathyroidectomy led to cure of the disease.

PMID- 22622070
TI  - From the lost radium files: misadventures in the absence of training, regulation,
      and accountability.
AB  - PURPOSE: Radium was the foundation of brachytherapy in the early decades of the
      20th century. Despite being a most precious and perilous substance, it was
      mislaid with surprising frequency. This essay explores how it was lost, the
      efforts taken to recover it, and measures instituted to prevent mishandling.
      METHODS AND MATERIALS: Review of contemporary literature, government
      publications, archives, and lay press. RESULTS: Radium is a particularly
      dangerous substance because of its long half-life, its gaseous daughter (radon),
      and the high-energy emissions of its decay products. Despite the hazard, it was
      unregulated for most of the century. Any physician could obtain and administer
      it, and protocols for safe handling were generally lacking. Change came with
      appreciation of the danger, regulation, mandated training, and the institution of
      a culture of accountability. Unfortunately, careless management of medical
      radionuclides remains a global hazard. CONCLUSION: Responsible stewardship of
      radioactive material was not a high priority, for practitioners or the federal
      government, for much of the 20th century. As a result, large quantities of radium
      had gone astray, possibly subjecting the general public to continued radiation
      exposure. Lessons from the radium era remain relevant, as medical radionuclides
      are still mishandled.

PMID- 22622069
TI  - Thiourea compound AW00178 sensitizes human H1299 lung carcinoma cells to TRAIL
      mediated apoptosis.
AB  - The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers
      apoptosis in a wide variety of cancer cells. Recently, cancer cell resistance to
      TRAIL-mediated apoptosis has become a challenging issue in the development of
      TRAIL-based anti-cancer therapies. In this study, we found that 1-(5-chloro-2
      methyl-phenyl)-3-[4-(5-trifluoromethyl-pyrazol-1-yl)-phenyl]-thiourea (AW00178)
      was able to sensitize TRAIL-resistant human lung cancer H1299 cells to TRAIL
      mediated apoptosis. Treatment with AW00178, either alone or in combination with
      TRAIL, induced the expression of CHOP, a protein related to TRAIL sensitivity,
      and reduced the expression of survivin, an anti-apoptotic protein involved in
      TRAIL resistance. Additionally, AW00178, alone or in combination with TRAIL,
      induced the activation of c-Jun and inactivation of Akt. A pharmacologic
      inhibition study revealed that c-Jun activation and Akt inactivation were
      strongly related to CHOP induction and survivin down-regulation, respectively. In
      summary, these results suggested that AW00178 mediated sensitization to TRAIL
      mediated apoptosis in H1299 cells by increasing sensitivity and decreasing
      resistance to TRAIL via the induction of c-Jun-dependent CHOP expression and the
      reduction of Akt-dependent survivin expression, respectively.

PMID- 22622071
TI  - Long-term sertraline treatment increases expression and decreases phosphorylation
      of glycogen synthase kinase-3B in platelets of patients with late-life major
      depression.
AB  - BACKGROUND: Abnormal regulation of glycogen synthase kinase 3-beta (GSK3B)
      activity has been implicated in the pathophysiology of mood disorders. Many
      pharmacological agents, including antidepressants, can modulate GSK3B. The aim of
      the present study was to investigate the effect of short-and long-term sertraline
      treatment on the expression and phosphorylation of GSK3B in platelets of patients
      with late-life major depression. METHODS: Thirty-nine unmedicated elderly adults
      with major depressive disorder (MDD) were initially included in this study. The
      comparison group comprised 18 age-matched, healthy individuals. The expression of
      total and Ser-9 phosphorylated GSK3B (pGSK3B) was determined by Enzyme
      Immunometric Assay (EIA) in platelets of patients and controls at baseline, and
      after 3 and 12 months of sertraline treatments for patients only. During this
      period, patients were continuously treated with therapeutic doses of sertraline.
      GSK3B activity was indirectly estimated by calculating the proportion of inactive
      (phosphorylated) forms (pGSK3B) in relation to the total expression of the enzyme
      (i.e., GSK3B ratio). RESULTS: Depressed patients had significantly higher levels
      of pGSK3B as compared to controls (p < 0.001). Within the MDD group, after 3
      months of sertraline treatment no significant changes were observed in GSK3B
      expression and phosphorylation state, as compared to baseline levels. However,
      after 12 months of treatment we found a significant increase in the expression of
      total GSK3B (p = 0.05), in the absence of any significant changes in pGSK3B (p =
      0.12), leading to a significant reduction in GSK3B ratio (p = 0.001).
      CONCLUSIONS: Our findings indicate that GSK3B expression was upregulated by the
      continuous treatment with sertraline, along with an increment in the proportion
      of active forms of the enzyme. This is compatible with an increase in overall
      GSK3B activity, which may have been induced by the long-term treatment of late
      life depression with sertraline.

PMID- 22622072
TI  - SLC6A4 rare variant associated with eating disorders in Mexican patients.

PMID- 22622074
TI  - Prediction of wastewater dilution and indicator bacteria concentrations for
      marine outfall systems.
AB  - This paper describes a modeling study of near-field and far-field dilution of
      discharged effluents from a deep sea outfall system in Antalya Bay of Turkey.
      Initial dilution and wastewater plume behavior were simulated by Visual Plumes
      UM3 model whereas Brooks dispersion model and first order bacterial decay
      formulations were used to simulate far-field dilution. The input data sets were
      collected by detailed field and lab investigations for effluent discharges (flow
      rate, total and fecal coliform concentration) and ambient environment
      (oceanographic and current measurements). Geostatistical methods and GIS were
      used to visualize results of the bacteriological sampling study. Site specific
      bacterial inactivation rates were determined by both in-situ and lab-scale
      experiments. Total dilution values and bacteria concentrations were predicted.
      Good agreement between predicted and measured total and fecal coliform
      concentrations were obtained for homogeneous and density stratified ambient
      conditions. Discussion on wastewater dilution mechanisms was presented with
      recommendations for similar future studies.

PMID- 22622073
TI  - Safety and efficacy of surgical treatment of carotid stump syndrome: pilot study.
AB  - Surgical exclusion of the internal carotid artery (ICA) stump combined with
      endarterectomy of the external carotid artery is an established treatment
      approach. The aim of this pilot study was to compare the risk of cerebrovascular
      events between surgical treatment and best medical treatment in patients with ICA
      occlusion and carotid stump syndrome. Forty patients (23 males; age: 43-80 years;
      mean age: 61.1 +/- 9.0 years) with carotid occlusion and carotid stump syndrome
      were enrolled. Ten patients with asymptomatic ICA occlusion and 10 patients with
      symptomatic ICA occlusion and carotid stump syndrome were enrolled to the best
      medical therapy group. Patients with chronic ICA occlusion, carotid stump
      syndrome, and one (15 patients) or recurrent (three patients) episodes of
      ipsilateral stroke or transient ischemic attack were enrolled to the surgical
      group. Neurological examination was undertaken on the day of randomization and
      then every 6 months in all patients for 4 years. All vascular events and death
      were recorded. Only one vascular event occurred in patients with symptomatic ICA
      occlusion without recurrent stroke or transient ischemic attack who were treated
      medically. No other vascular event was noted in the other subgroups. One patient
      with symptomatic carotid occlusion without recurrent stroke died due to
      myocardial infarction 6 months after surgery. Surgical treatment of carotid stump
      syndrome seems to be a safe procedure. Nevertheless, the benefit of a surgical
      approach in comparison with the best medical treatment is not clear.

PMID- 22622075
TI  - Energy homeostasis as an integrative tool for assessing limits of environmental
      stress tolerance in aquatic invertebrates.
AB  - Energy balance is a fundamental requirement of stress adaptation and tolerance.
      We explore the links between metabolism, energy balance and stress tolerance
      using aquatic invertebrates as an example and demonstrate that using key
      parameters of energy balance (aerobic scope for growth, reproduction and
      activity; tissue energy status; metabolic rate depression; and compensatory onset
      of anaerobiosis) can assist in integrating the effects of multiple stressors and
      their interactions and in predicting the whole-organism and population-level
      consequences of environmental stress. We argue that limitations of both the
      amount of available energy and the rates of its acquisition and metabolic
      conversions result in trade-offs between basal maintenance of a stressed organism
      and energy costs of fitness-related functions such as reproduction, development
      and growth and can set limit to the tolerance of a broad range of environmental
      stressors. The degree of stress-induced disturbance of energy balance delineates
      transition from moderate stress compatible with population persistence (pejus
      range) to extreme stress where only time-limited existence is possible (pessimum
      range). It also determines the predominant adaptive strategy of metabolic
      responses (energy compensation vs. conservation) that allows an organism to
      survive the disturbance. We propose that energy-related biomarkers can be used to
      determine the conditions when these metabolic transitions occur and thus predict
      ecological consequences of stress exposures. Bioenergetic considerations can also
      provide common denominator for integrating stress responses and predicting
      tolerance limits under the environmentally realistic scenarios when multiple and
      often variable stressors act simultaneously on an organism. Determination of
      bioenergetic sustainability at the organism's level (or lack thereof) has
      practical implications. It can help identify the habitats and/or conditions where
      a population can survive (even if at the cost of reduced reproduction and growth)
      and those that are incapable of supporting viable populations. Such an approach
      will assist in explaining and predicting the species' distribution limits in the
      face of the environmental change and informing the conservation efforts and
      resource management practices.

PMID- 22622076
TI  - Return to normal life after AIDS as a reason for lost to follow-up in a community
      based antiretroviral treatment program.
AB  - OBJECTIVES: To understand reasons for lost-to-follow-up (LTFU) from a community
      based antiretroviral therapy program in Uganda. STUDY DESIGN: Retrospective
      cohort of patients LTFU between May 31, 2001, to May 31, 2010, was examined. A
      representative sample of 579 patients traced to ascertain their outcomes.
      METHODS: Mixed methods were used. Using "stopped care" as the hazard and "self
      transferred" as the comparator, we examined using Cox proportional multivariable
      model risk factors for stopping care. RESULTS: Overall, 2933 of 3954 (74.0%)
      patients were LTFU. Of 579 of 2933 (19%) patients sampled for tracing, 32 (5.5%)
      were untraceable, 66(11.4 %) were dead, and 481 (83.0%) found alive. Of those
      found alive, 232 (40.0%) stopped care, 249 (43.0%) self-transferred, whereas 61
      (12.7%) returned to care at Reach Out Mbuya HIV/AIDS Initiative. In adjusted
      hazards ratios, born-again religion, originating from outside Kampala, resident
      in Kampala for <5 years but >1 year, having school-age children who were out of
      school, non-HIV disclosure, CD4 counts >250 cells per cubic millimeter and pre
      antiretroviral therapy were associated with increased risk of stopping care.
      Qualitative interviews revealed return to a normal life as a key reason for LTFU.
      Of 61 patients who returned to care, their median CD4 count at LTFU was higher
      than on return into care (401/mm3 vs. 205/mm3, P < 0.0001). CONCLUSIONS: Many
      patients become LTFU during the course of years, necessitating the need for
      effective mechanisms to identify those in need of close monitoring. Efforts
      should be made to improve referrals and mechanisms to track patients who transfer
      to different facilities. Additionally, tracing of patients who become LTFU is
      required to convince them to return.

PMID- 22622077
TI  - Addressing poor retention of infants exposed to HIV: a quality improvement study
      in rural Mozambique.
AB  - OBJECTIVE: Early infant diagnosis (EID) is the first step in HIV care, yet 75% of
      HIV-exposed infants born at 2 hospitals in Mozambique failed to access EID.
      DESIGN: Before/after study. SETTING: Two district hospitals in rural Mozambique.
      PARTICIPANTS: HIV-infected mother/HIV-exposed infant pairs (n = 791).
      INTERVENTION: We planned 2 phases of improvement using quality improvement
      methods. In phase 1, we enhanced referral by offering direct accompaniment of new
      mothers to the EID suite, increasing privacy, and opening a medical record for
      infants before postpartum discharge. In phase 2, we added enhanced referral
      activity as an item on the maternity register to standardize the process of
      referral. MAIN OUTCOME MEASURE: The proportion of HIV-infected mothers who
      accessed EID for their infant <90 days of life. RESULTS: We tracked mother/infant
      pairs from June 2009 to March 2011 (phase 0: n = 144; phase 1: n = 479; phase 2:
      n = 168), compared study measures for mother/infant pairs across intervention
      phases with chi2, estimated time-to-EID by Kaplan-Meier, and determined the
      likelihood of EID by Cox regression after adjusting for likely barriers to follow
      up. At baseline (phase 0), 25.7% of infants accessed EID <90 days. EID improved
      to 32.2% after phase 1, but only 17.3% had received enhanced referral. After
      phase 2, 61.9% received enhanced referral and 39.9% accessed EID, a significant 3
      phase improvement (P = 0.007). In adjusted analysis, the likelihood of EID at any
      time was higher in the phase 2 group versus phase 0 (adjusted hazard ratio: 1.68,
      95% confidence interval: 1.19 to 2.37, P = 0.003). CONCLUSIONS: Retention
      improved by 55% with a simple referral enhancement. Quality improvement efforts
      could help improve care in Mozambique and other low-resource countries [added].

PMID- 22622078
TI  - Nonmelanoma skin cancers among HIV-infected persons in the HAART era.

PMID- 22622079
TI  - Hepatitis E virus as a causative agent of unexplained liver enzyme elevations in
      HIV-infected patients.

PMID- 22622080
TI  - Child Status Index validation study by Sabin et al misses the mark.

PMID- 22622082
TI  - Research letter: is neuroticism a risk factor for postpartum depression?

PMID- 22622083
TI  - Osh6 overexpression extends the lifespan of yeast by increasing vacuole fusion.
AB  - In yeast cells, the vacuole divides and fuses in each round of cell cycle. While
      mutants defective in vacuole fusion are "wild type" for vegetative growth, most
      have shortened replicative lifespans under caloric restriction (CR) condition, a
      manipulation that extends lifespan in wild type cells. To explore whether vacuole
      fusion extends lifespan, we screened for genes that can complement the fusion
      defect of selected mutants (erg6Delta, a sterol mutant; nyv1Delta,  a mutant
      involved in the vacuolar SNARE complex and vac8Delta, a vacuolar membrane protein
      mutant). This screen revealed that Osh6, a member of the oxysterol-binding
      protein family, can complement the vacuole fusion defect of nyv1Delta, but not
      erg6Delta or vac8Delta, suggesting that Osh6's function in vacuole fusion is
      partly dependent on membrane ergosterol and Vac8. To measure the effect of OSH6
      on lifespan, we replaced the endogenous promoter of OSH6 with a shorter version
      of the ERG6 promoter to obtain PERG6-OSH6. This mutant construct significantly
      extended the replicative lifespan in a wild type background and in a nyv1Delta
      mutant. Interestingly, PERG6-OSH6 cells were more sensitive to drugs that inhibit
      the activity of the TOR complex 1 (TORC1) than wild type cells. Moreover, a PERG6
      OSH6 tor1Delta double mutant demonstrated a greatly shortened lifespan,
      suggesting a genetic interaction between Osh6 and Tor1. Since active TORC1
      stimulates vacuole scission and CR downregulates TORC1, Osh6 may link these two
      pathways by adjusting vacuolar membrane organization to extend lifespan.

PMID- 22622084
TI  - DAPk silencing by DNA methylation conveys resistance to anti EGFR drugs in lung
      cancer cells.

PMID- 22622085
TI  - Insights from a new tool for meiotic induction in fission yeast.

PMID- 22622086
TI  - Appearance and heterochromatin localization of HP1alpha in early mouse embryos
      depends on cytoplasmic clock and H3S10 phosphorylation.
AB  - Pericentric constitutive heterochromatin surrounds centromeric regions and is
      important for centromere function and chromatid cohesion. HP1 (heterochromatin
      protein 1), a homolog of yeast Swi6, has been shown to be indispensible for
      proper heterochromatin structure and function. In mammalian somatic cells, two
      HP1 isoforms, HP1alpha and HP1beta, are constitutively present in pericentric
      heterochromatin until late G 2, when they dissociate from heterochromatin.
      Subsequently, they re-associate with heterochromatin at late anaphase. In one
      cell mouse embryos, pericentric heterochromatin has a unique configuration and
      features. It does not form heterochromatin clusters observed in somatic cells and
      known as chromocenters. Instead, in both pronuclei, it surrounds nucleolar
      precursor bodies (NBPs), forming ring-like structures. These regions contain
      HP1beta but lack HP1alpha in both pronuclei. In subsequent interphases, HP1beta
      is constitutively found in heterochromatin until the blastocyst stage. It is not
      known when HP1alpha appears and what is its function in early mouse embryos.
      Here, we show that HP1alpha appears for the first time at late S phase of two
      cell stage, at the time when pericentric heterochromatin is replicated. Its
      appearance is regulated at the level of translation. In two-cell embryos, the
      amount of HP1alpha that can bind to these regions is regulated by phosphorylation
      of serine 10 of histone H3 (H3S10Ph). Elimination of HP1alpha by siRNA interfered
      with centromere relocation from heterochromatin surrounding NPBs to pro
      chromocenters at the two-cell stage but did not affect preimplantation develoment
      to the blastocyst stage.

PMID- 22622087
TI  - Cdk5-induced neuronal cell death: the activation of the conventional Rb-E2F G 1
      pathway in post-mitotic neurons.

PMID- 22622088
TI  - A killer promoting survival: p53 as a selective means to avoid side effects of
      chemotherapy.

PMID- 22622090
TI  - Treatment of Mason type II radial head fractures without associated fractures or
      elbow dislocation: a systematic review.
AB  - PURPOSE: There is no consensus as to the best treatment of Mason type II
      fractures without concomitant elbow fractures or dislocation. The aim of this
      systematic review was to compare the results of operative and nonoperative
      treatment of these injuries. METHODS: We systematically screened the databases of
      PubMed, EMBASE, and Cochrane Library until September 2011 for studies on
      nonoperative or operative treatment of Mason type II fractures. We defined
      successful treatment as an excellent or good result according to the Broberg and
      Morrey score, Mayo Elbow Performance Score, or Radin score. Exclusion criteria
      were duration of follow-up of less than 6 months, an improperly described therapy
      or combination of therapies, skeletal immaturity, and articles written in
      languages other than English. RESULTS: Among 717 studies, 9 retrospective case
      series (level IV) describing 224 patients satisfied our inclusion criteria.
      Nonoperative treatment was successful in 114 of 142 patients (80%) pooled from
      the studies (42% to 96% success in individual studies). Open reduction and
      internal fixation was successful in 76 of 82 patients (93%) (81% to 100% success
      in individual studies). CONCLUSIONS: Only a few studies with a low level of
      evidence address the treatment of isolated, displaced, partial articular
      fractures. There is a need for sufficiently powered randomized, controlled
      trials. CLINICAL RELEVANCE: There is insufficient evidence to draw firm
      conclusions on the optimal treatment of isolated, displaced, partial articular
      Mason type II fractures.

PMID- 22622091
TI  - Adult awareness of tobacco advertising, promotion, and sponsorship--14 countries.
AB  - According to the 2012 Report of the U.S. Surgeon General, exposure to tobacco
      advertising, promotion, and sponsorship (TAPS) is associated with the initiation
      and continuation of smoking among young persons. The World Health Organization
      (WHO) Framework Convention on Tobacco Control (FCTC) requires countries to
      prohibit all forms of TAPS; the United States signed the agreement in 2004, but
      the action has not yet been ratified. Many countries have adopted partial bans
      covering direct advertising in traditional media channels; however, few countries
      have adopted comprehensive bans on all types of direct and indirect marketing. To
      assess progress toward elimination of TAPS and the level of awareness of TAPS
      among persons aged >=15 years, CDC used data from the Global Adult Tobacco Survey
      (GATS) collected in 14 countries during 2008-2010. Awareness of any TAPS ranged
      from 12.4% in Turkey to 70.4% in the Philippines. In the four countries where
      awareness of TAPs was <=15%, three of the countries had comprehensive bans
      covering all nine channels assessed by GATS, and the fourth country banned seven
      of the nine channels. In 12 countries, more persons were aware of advertising in
      stores than advertising via any other channel. Reducing exposure to TAPS is
      important to prevent initiation of tobacco use by youths and young adults and to
      help smokers quit.

PMID- 22622092
TI  - State tobacco revenues compared with tobacco control appropriations--United
      States, 1998-2010.
AB  - In 1999, CDC published Best Practices for Comprehensive Tobacco Control, which
      outlined the elements of an evidence-based state tobacco control program and
      provided a recommended state funding range to substantially reduce tobacco
      related disease, disability, and death. Best Practices recommended that states
      invest a combined $1.6-$4.2 billion annually in such programs and subsequently
      updated that recommendation to $3.7 billion annually in 2007. To analyze states'
      historical investments in tobacco control and calculate the amount of funding
      necessary to achieve Best Practices recommendations, CDC tracked data from 1998
      to 2010. During this period, states collected $243.8 billion in total tobacco
      revenues from tobacco industry settlement payments and cigarette excise taxes.
      State and federal appropriations for tobacco control totaled $8.1 billion,
      whereas CDC's Best Practices recommended funding of at least $29.2 billion ($1.6
      billion for 9 years plus $3.7 billion for 4 years). For the entire study period,
      the ratio of state tobacco revenues to state and federal tobacco control
      appropriations was approximately 30 to 1 ($243.8 billion to $8.1 billion); in
      2010, the ratio was approximately 37 to 1 ($23.96 billion to $0.64 billion). If
      states allocated funding for tobacco control at Best Practices levels, they could
      achieve larger and more rapid reductions in smoking and associated morbidity and
      mortality.

PMID- 22622093
TI  - Work-related asthma--38 states and District of Columbia, 2006-2009.
AB  - Work-related asthma (WRA) includes work-exacerbated asthma (preexisting or
      concurrent asthma worsened by factors related to the workplace environment) and
      occupational asthma (new onset asthma attributed to the workplace environment).
      WRA is a preventable occupational lung disease associated with serious adverse
      health and socioeconomic outcomes. Among workers with similar occupational
      exposures, WRA diagnosis offers unique opportunities for prevention. The American
      Thoracic Society estimated that 15% of U.S. adults with asthma have asthma
      attributable to occupational factors. State-level information on the proportion
      of asthma that is WRA is limited but could be useful to prioritize and guide
      investigations and interventions. To estimate current asthma prevalence and the
      proportion of asthma that is WRA, CDC analyzed data from the 2006-2009 Behavioral
      Risk Factor Surveillance System (BRFSS) from 38 states and the District of
      Columbia (DC). This report summarizes the results of that analysis, which
      indicated that among ever-employed adults with current asthma, the overall
      proportion of current asthma that is WRA was 9.0%. State-specific proportions of
      asthma that are WRA ranged from 4.8% to 14.1%. Proportions of WRA were highest
      among persons aged 45-64 years (12.7%), blacks (12.5%), and persons of other
      races (11.8%). These findings provide a baseline that state and national health
      agencies can use to monitor the proportion of WRA among persons with current
      asthma. Enhancing WRA surveillance through routine collection of industry and
      occupation information will greatly increase understanding of WRA.

PMID- 22622094
TI  - Prevalence of stroke--United States, 2006-2010.
AB  - In 2008, mortality from stroke was the fourth leading cause of death in the
      United States, and stroke was a leading cause of long-term severe disability.
      Nearly half of older stroke survivors experience moderate to severe disability.
      Care for stroke survivors cost an estimated $18.8 billion in the United States
      during 2008, and lost productivity and premature mortality cost an additional
      $15.5 billion. A 3.6% decline in stroke mortality during 2007-2008 means that the
      prevalence of stroke (defined in this report as the percentage of
      noninstitutionalized persons who have ever experienced stroke) will increase if
      stroke incidence and the mean length of post-stroke survival does not decrease
      and the proportion of institutionalized stroke survivors does not change.
      Measuring the prevalence of stroke at the state level enables CDC and state
      health officials to target resources to populations or regions with high
      prevalence. A previous report of state-level stroke prevalence used 2005
      Behavioral Risk Factor Surveillance System (BRFSS) data. To measure recent trends
      in stroke prevalence by sociodemographic characteristics and state of residence,
      CDC analyzed 2006-2010 data from BRFSS. This report describes the results of that
      analysis, which indicated that during this period, overall self-reported stroke
      prevalence did not change. However, consistent with findings in the previous
      report, there were disparities in stroke prevalence identified by age,
      race/ethnicity, and level of education. Specifically, older adults, blacks,
      American Indians/Alaska Natives, persons with lower levels of education, and
      persons living in the southeastern United States had higher stroke prevalence.

PMID- 22622095
TI  - Pulmonary embolism in the emergency department: a Singaporean nursing case
      review.
AB  - INTRODUCTION: The presentation of pulmonary embolism to the emergency department
      (ED) can prove challenging because of the myriad of potential disease processes
      that mimic its signs and symptoms. The incidence of pulmonary embolism and indeed
      the mortality associated with it is relatively high. Early diagnosis and
      treatment is crucial in off-setting the potential deleterious effects associated
      with this condition. The aim of this article is to present a nursing case review
      of a patient presenting to the ED with a diagnosis of pulmonary embolism. METHOD:
      We chose to use a case review to highlight the nursing and medical care that was
      provided for a patient who presented to the emergency department acutely with
      dyspnoea, chest pain and pyrexia. The use of case reviews are useful in reporting
      unusual or rare cases and this format is typically seen more in medicine than in
      nursing. They can naturally take one of two formats-a single case report or a
      series of case reports; in this case we opted to report on a single case.
      DISCUSSION: The gentleman in question was an ambulance admission to the ED with a
      three day history of chest pain, shortness of breath and one episode of syncope
      which brought him to the ED. Over the course of his admission a variety of
      treatment modalities were used successfully to alleviate the problem. More
      notable from a nursing perspective was the use of diagnostic tools as an
      interpretation to guide his care and provide a platform from which a deeper
      understanding and appreciation of the intricacies the critically ill patient
      often presents. CONCLUSION: We found the use of case review very enlightening in
      understanding the disease process and the decision-making that accompanies this.
      Whilst our patient was successfully rehabilitated home, we learnt a lot from the
      experience which has been most beneficial in supporting our understanding of
      pulmonary embolism.

PMID- 22622096
TI  - Parental employment, family routines and childhood obesity.
AB  - Using the Early Childhood Longitudinal Survey-Kindergarten Class of 1998-1999
      (ECLS-K) data from kindergarten through eighth grade, this paper investigate the
      relationships among maternal employment, family routines and obesity. More hours
      worked by the mother tend to be negatively related to positive routines like
      eating meals as a family or at regular times, or having family rules about hours
      of television watched. Many of these same routines are significantly related to
      the probability of being obese, implying that family routines may be a mechanism
      by which maternal employment intensity affects children's obesity. However,
      inclusion of family routines in the obesity regression does not appreciably
      change the estimated effect of maternal employment hours. Thus, the commonly
      estimated deleterious effect of maternal employment on children's obesity cannot
      be explained by family routines, leaving the exact mechanisms an open question
      for further exploration.

PMID- 22622097
TI  - Radiation dose to surgeons in theatre.
AB  - OBJECTIVES: To evaluate the effects of ionising radiation and radiation limits,
      and measure radiation doses received by surgeons in theatre. DESIGN:
      Thermoluminescent dosimeter measurements of accumulated dose to specific
      anatomical regions of a neurosurgeon, gastroenterologist and orthopaedic surgeon
      performing fluoroscopy on 39 patients undergoing treatment for back pain, 7 for
      endoscopic retrograde cholangiopancreatography procedures, and 48 for orthopaedic
      operations respectively. RESULTS: Radiation dose levels with the X-ray tube above
      the table during back pain procedures exceeded the occupational annual
      recommendation to the neurosurgeon's hands. The protocol regarding the
      orientation of the C-arm was changed. Convincing evidence of the importance and
      effectiveness of lead shielding was recorded. CONCLUSIONS: Constant revision of
      protocols should apply the as-low-as-reasonably-achievable principle in every
      unique setting. The ideal is to position the image intensifier above the theatre
      table. The longest possible distance from the source will lower radiation risk.
      Full-body protection of 0.35 mm lead equivalence during fluoroscopy is mandatory.

PMID- 22622098
TI  - Laparotomy for blunt abdominal trauma in a civilian trauma service.
AB  - This report looks at the group of patients who required a laparotomy for blunt
      torso trauma at a busy metropolitan trauma service in South Africa.  Methods. A
      prospective trauma registry is maintained by the surgical services of the
      Pietermaritzburg metropolitan complex. This registry is interrogated
      retrospectively. All patients who required admission for blunt torso trauma over
      the period September 2006 - September 2007 were included for review. Proformas
      documenting mechanism of injury, age, vital signs, blood gas, delay in
      presentation, length of hospital stay, intensive care unit stay and operative
      details were completed.  Results. A total of 926 patients were treated for blunt
      trauma by the Pietermaritzburg metropolitan services during the period under
      consideration. A cohort of 65 (8%) required a laparotomy for blunt trauma during
      this period. There were 17 females in this group. The mechanisms of injury were
      motor vehicle accident (MVA) (27), pedestrian vehicle accident (PVA) (21),
      assault (5), fall from a height (3), bicycle accident (6), quad bike accident (1)
      and tractor-related accident (2). The following isolated injuries were discovered
      at laparotomy: liver (9), spleen (5), diaphragm (1), duodenum (2), small bowel
      (8), mesentery (8) bladder (10), gallbladder (1), stomach (2), colon/rectum (2)
      and retrohepatic vena cava (1). The following combined injuries were discovered:
      liver and diaphragm (2), spleen and pancreas (1), spleen and liver (2), spleen,
      aorta and diaphragm (1), spleen and bladder (1) and small bowel and bladder (2).
      Eighteen patients in the series (26%) required relaparotomy. In 10 patients
      temporary abdominal containment was needed. The mortality rate was 26% (18
      patients). There were 6 deaths from massive bleeding, all within 6 hours of
      operation, and 3 deaths from renal failure; the remaining 9 patients died of
      multiple organ failure. There were 8 negative laparotomies (7%). In the negative
      laparotomy group false-positive computed tomography (CT) scan findings were a
      problem in 3 cases, in 1 case hypotension and a fractured pelvis on admission
      prompted laparotomy, and in the other cases clinical findings prompted
      laparotomy. All patients who underwent negative laparotomy survived. There were
      10 pelvic fractures, 5 lower limb fractures, 2 spinal injuries, 4 femur fractures
      and 2 upper limb fractures. CT scans were done in 25 patients. In 20 patients the
      systolic blood pressure on presentation was <90 mmHg and in 41 the pulse rate was
      >110 beats/min. In 16 patients there was a base excess of <-4 on presentation. 
      Conclusion. Laparotomy is needed in less than 10% of patients who sustain blunt
      abdominal trauma. Solid visceral injury requiring laparotomy presents with
      haemodynamic instability. Hollow visceral injury has a more insidious
      presentation and is associated with a delay in diagnosis. CT scan is the most
      widely used investigation in blunt abdominal trauma. It is both sensitive and
      specific for solid visceral injury, but its accuracy for the diagnosis of hollow
      visceral injury is less well defined. Clinical suspicion must be high, and hollow
      visceral injury needs to be actively excluded.

PMID- 22622099
TI  - Repair of abdominal aortic aneurysms with aorto-uni-iliac stentgraft and femoro
      femoral bypass.
AB  - Endovascular repair (EVAR) is accepted as effective treatment for abdominal
      aortic aneurysms (AAAs) and has become the standard of care in many instances.
      The standard bifurcated stentgraft (BFG) is often not possible in patients with
      unfavourable aneurysm morphology. The aorto-uni-iliac (AUI) graft configuration
      with femoro-femoral bypass (FFBP) is a promising alternative which may extend the
      scope of EVAR for AAAs. The aim of this study was to evaluate the feasibility,
      efficacy and durability of AUI with FFBP.    Design. The results of a single
      institution and a single surgeon were prospectively collected from January 2002
      to August 2010. All patients were followed up at 1, 3, 6 and 12 months and then
      annually.    Results. There were 33 patients (27 males) with a mean age of 71.7
      years (range 46 - 84). Open surgery posed an unacceptably high risk to all
      patients owing to advanced age and/or American Society of Anesthesiologists (ASA)
      classification 3/4. Ineligibility for BFG was due to unfavourable anatomy or a
      combination of factors in most cases (31 patients). Two patients had anastomotic
      aneurysms after previous open surgery.     The technical success rate was 100%.
      One severe intra-operative complication occurred (perforated iliac artery). Two
      patients (ASA 4) died within 30 days (peri-operative mortality rate 6.1%). Seven
      patients (21.1%) developed postoperative wound complications. Eight patients died
      during follow-up of non-aneurysm-related conditions. Twenty-three patients are
      alive, with mean follow-up of 24.4 months and a survival rate of 69.7%. Two
      complications occurred during long-term follow-up, namely 1 case of graft sepsis
      and 1 of FFBP occlusion.     Conclusion. AUI with FFBP is a safe, effective and
      durable alternative in high-risk patients with AAAs where standard open repair is
      contraindicated and BFG repair is not possible owing to unfavourable aneurysm
      morphology.

PMID- 22622100
TI  - Intussusception in children: experience with 105 patients in a department of
      paediatric surgery, Turkey.
AB  - AIM: The aim of this study was to present our experience in patients with
      intussusception (IN). MATERIALS AND METHODS: One hundred and five cases of IN
      treated between 1991 and 2007 were analysed. Age, gender, symptoms, signs,
      diagnostic and treatment methods, types of IN including leading point, and
      postoperative complications were evaluated. RESULTS: The mean age of the patients
      was 2.5 years (range 1 month - 15 years). Fifty-nine per cent (62/105) were under
      1 year of age, and of these 28% were receiving therapy for upper respiratory
      tract infection. The most common symptom was colicky abdominal pain. Rectal
      bleeding was present in all patients under 2 years of age. In 23 children (21.9%)
      leading points were detected. Thirty per cent of the patients were older than 4
      years, and 76.6% of these had leading points. Ultrasonography demonstrated the
      invaginated segment in 93 patients. Hydrostatic reduction was attempted in 71.4%
      (75) of the patients and was successful in 48% (36), 70% of whom were under 1
      year of age. Of the patients with unsuccessful hydrostatic reduction, 11 required
      intestinal resection and primary anastomosis and 35 manual reduction. Twenty-four
      patients were diagnosed by means of ultrasonography and were operated on
      immediately. Ten of these patients had signs of peritonitis on admission and were
      treated by resection-primary anastomosis. CONCLUSION: In patients with IN under 2
      years of age, hydrostatic or pneumatic reduction may be successful. Considering
      the high incidence of leading points in older children, one should not persist
      with reduction but should rather design a treatment plan accordingly, i.e.
      laparotomy with manual reduction or resection.

PMID- 22622101
TI  - Association between low serum free testosterone and adverse prognostic factors in
      men diagnosed with prostate cancer in KwaZulu-Natal.
AB  - BACKGROUND: The association of serum free testosterone (FT) with prostate cancer
      is not fully understood. Studies on the results of the relationship between serum
      testosterone level and prostate cancer are conflicting. However, there is a
      reported association between lower serum testosterone levels and high-grade
      prostate cancer. OBJECTIVE: To investigate the relationship between serum FT and
      the clinico-pathological characteristics of prostate cancer in South African
      patients. MATERIALS AND METHODS: The clinical data of 109 consecutive patients
      diagnosed with prostate cancer on biopsy were evaluated prospectively. The
      variables were age, ethnic group, prostate specific antigen (PSA), digital rectal
      examination (DRE) findings, clinical tumour, nodes and metastases (TNM) stage,
      and Gleason score. Low serum FT was defined as <250ng/dl. Statistical analysis
      was performed using Stata V10 software (p<0.05 considered significant). RESULTS:
      There was a statistically significant association between low serum FT and high
      serum PSA, high Gleason score and clinically advanced stage prostate cancer.
      CONCLUSIONS: In this cohort of men with histologically diagnosed prostate cancer,
      low serum FT was associated with higher PSA, higher grade, and locally advanced
      or metastatic prostate cancer.

PMID- 22622102
TI  - Jejuno-jejunal intussusception secondary to small-bowel lipomatosis: a case
      report.
AB  - Intussusception is usually a disease of children aged between 6 months and 4
      years, in which a part of a bowel telescopes into another part of the bowel. We
      report a case in a 60-year-old man who required resection and anastomosis.
      Although intussusception is unusual in adults, awareness of the differences in
      symptoms and causes should be borne in mind when adults present with intestinal
      obstruction.

PMID- 22622103
TI  - Mucinous cystadenoma arising in a completely isolated infected ileal duplication
      cyst.
AB  - Gastrointestinal duplications are uncommon congenital lesions that can occur
      anywhere along the alimentary tract, and the symptoms of which generally develop
      during infancy or childhood. Completely isolated duplication cysts are an
      extremely rare variant of duplication, where no communication between the cyst
      and the adjacent bowel segment is present. We report the unique case of an adult
      who presented with right lower abdominal pain and systemic signs of inflammation
      caused by infection of a completely isolated ileal duplication cyst. Histological
      examination of the cyst additionally revealed a low-grade mucinous cystadenoma.
      We discuss the clinical presentations, diagnosis and treatment of this rare
      entity.

PMID- 22622104
TI  - Buccal fat pad - a simple, underutilised flap.
AB  - The pedicled buccal fat pad is a reliable flap for the repair of small oral
      defects. It is durable, easy to harvest and should be considered in settings
      where access to free flaps is limited and in cases where previous flaps have
      failed. We discuss a case where this flap was used successfully for closure of an
      oro-antral fistula. The indications, anatomy and techniques of successful harvest
      are discussed.

PMID- 22622105
TI  - Pictorial Interlude: caught up in a 'whirl'.
AB  - A patient with the 'whirl sign' on computed tomography (CT) is 25.3 times as
      likely as a patient without to have small-bowel obstruction (SBO) necessitating
      surgery. There is therefore an important role for the 'whirl sign' in assessment
      of patients with clinical and radiological signs of SBO.

PMID- 22622106
TI  - Thyroglobulin and recurrence of thyroid cancer.

PMID- 22622107
TI  - Identification of viable myocardium in acute anterior infarction using duration
      of systolic lengthening by tissue Doppler strain: a preliminary study.
AB  - BACKGROUND: The aim of this study was to investigate whether strain Doppler
      echocardiography before reperfusion therapy could quantify ischemic dysfunction
      and predict viable myocardium in acute myocardial infarction as determined by
      magnetic resonance imaging. METHODS: Twenty-six patients (mean age, 60 +/- 12
      years; seven women) with acute myocardial infarctions who underwent acute
      percutaneous coronary intervention were examined using strain Doppler
      echocardiography immediately before the procedure. Percutaneous coronary
      intervention was performed 296 +/- 122 min after the onset of pain. Peak left
      ventricular systolic longitudinal strain and the duration of systolic lengthening
      were analyzed. Magnetic resonance imaging was performed 11 +/- 5 months after
      therapy. Scarring exceeding 50% of the segment area was considered nonviable.
      RESULTS: Peak systolic strain fell gradually (becoming less negative) from normal
      segments to segments with transmural infarction (P < .0001), and the duration of
      systolic lengthening increased (P < .0001). Myocardial scarring was closely
      correlated with peak systolic strain (R = 0.76, P < .00001) and the duration of
      systolic lengthening (R = 0.88, P < .00001). There was a significant correlation
      between the degree of scarring and time to percutaneous coronary intervention (R
      = 0.40, P = .045). In segments with systolic lengthening, the improvement in
      strain after remodeling was significantly higher (5.5 +/- 5.1%) than in segments
      with duration of systolic lengthening > 67% of systole (2.2 +/- 3.7%) (P < .001).
      Receiver operating characteristic curve analyses showed that duration of systolic
      lengthening > 67.3% could identify nonviable myocardium (sensitivity, 90%;
      specificity, 94%). CONCLUSIONS: In patients with acute myocardial infarctions in
      the anterior wall, strain measurements can identify myocardium with nontransmural
      scarring. The duration of systolic lengthening is a novel, easily implemented
      variable that may identify ischemic but viable myocardium. Myocardial infarctions
      in other left ventricular regions should be investigated in future studies.

PMID- 22622108
TI  - Impact of hypertension on ventricular-arterial coupling and regional myocardial
      work at rest and during isometric exercise.
AB  - BACKGROUND: To understand better the mechanism of left ventricular (LV)
      remodeling related to hypertension, it is important to evaluate LV function in
      relation to the changes in loading conditions. The aim of this study was to
      investigate changes in conventional ventricular-arterial coupling indexes, LV
      strain, and a new index reflecting regional myocardial work assessed
      noninvasively at rest and during isometric exercise in a random sample including
      participants with normal blood pressure and those with hypertension. METHODS: A
      total of 148 participants (53.4% women; mean age, 52.0 years; 39.2% with
      hypertension) underwent simultaneous echocardiographic and arterial data
      acquisition at rest and during increased afterload (handgrip exercise). End
      systolic pressure was determined from the carotid pulse wave. Arterial elastance
      (Ea) and LV elastance (Ees) were calculated as end-systolic pressure/stroke
      volume and end-systolic pressure/end-systolic volume. Doppler tissue imaging and
      two-dimensional speckle tracking were used to derive LV longitudinal strain.
      Regional myocardial work (ejection work density [EWD]) was the area of the
      pressure-strain loop during ejection. RESULTS: At rest, with adjustments applied,
      Ees (3.06 vs 3.71 mm Hg/mL, P = .0003), Ea/Ees (0.54 vs 0.47, P = .002) and EWD
      (670 vs 802 Pa/m(2), P = .0001) differed significantly between participants with
      normal blood pressure and those with hypertension. During handgrip exercise, Ea
      and Ea/Ees significantly increased (P < .0001) in both groups. Doppler tissue
      imaging and two-dimensional LV strain decreased in participants with hypertension
      (P <= .008). Only in subjects with normal blood pressure EWD significantly
      increased (+14.7%, P = .0009). CONCLUSIONS: Although patients with hypertension
      compared with those with normal blood pressure have increased LV systolic
      stiffness and regional myocardial work to match arterial load at rest, they might
      have diminished cardiac reserve to increase myocardial performance, as estimated
      by EWD during isometric exercise.

PMID- 22622109
TI  - Burkholderia cenocepacia infection: disruption of phagocyte immune functions
      through Rho GTPase inactivation.
AB  - Phagocytosis is an important component of innate immunity that contributes to the
      eradication of infectious microorganisms; however, successful bacterial pathogens
      often evade different aspects of host immune responses. A common bacterial
      evasion strategy entails the production of toxins and/or effectors that disrupt
      normal host cell processes and because of their importance Rho-family GTPases are
      often targeted. Burkholderia cenocepacia, an opportunistic pathogen that has a
      propensity to infect cystic fibrosis patients, is an example of a pathogenic
      bacterium that has only recently been shown to disrupt Rho GTPase function in
      professional phagocytes. More specifically, B. cenocepacia disrupts Rac and Cdc42
      seemingly through perturbation of guanine nucleotide exchange factor function.
      Inactivation of Rac, Cdc42 and conceivably other Rho GTPases seriously
      compromises phagocyte function.

PMID- 22622110
TI  - Nursing students with latex allergy.
AB  - Latex allergy affects millions of people in the general population and a higher
      percentage of health care workers. Nursing students with a latex sensitivity pose
      a unique challenge for the nurse educator. Students may enter the program with
      pre-existing latex allergy or develop the allergy during the educational process.
      This manuscript explores the implications of latex allergies exhibited by the
      nursing student. It addresses the responsibilities of the educator in the skills
      or simulation laboratory and during clinical learning experiences. It also offers
      suggestions for ensuring the safety of the student while reducing the legal
      liabilities of the educational program. The article addresses possible policy
      ramifications for nursing schools.

PMID- 22622111
TI  - Systemic inflammation after aortic cross clamping is influenced by Toll-like
      receptor 2 preconditioning and deficiency.
AB  - BACKGROUND: The perioperative morbidity and mortality of abdominal aortic
      aneurysm repair is linked to systemic inflammation. Important triggers of the
      latter are Toll-like receptors (TLRs), which play a central role in innate
      immunity. Ischemia/reperfusion (I/R) injury can be influenced by either TLR
      stimulation before I/R (preconditioning) or TLR dysfunction (deficiency or
      polymorphism). The influence of TLR2 stimulation or deficiency on systemic
      cytokine release and organ damage after aortic cross clamping has not been
      evaluated yet. METHODS: Wild type (WT) and TLR2-deficient mice were subjected to
      1 h ischemia and 2 or 4 h reperfusion of the infrarenal aorta. One group of WT
      mice was preconditioned with the synthetic TLR2 agonist Pam(3)Cys-Ser-Lys(4)
      (Pam(3)CSK(4)). Sham-operated animals without I/R served as controls. Plasma
      levels of interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12,
      granulocyte macrophage-colony stimulating factor, tumor necrosis factor-alpha,
      alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase
      (LDH), and creatinine were measured. RESULTS: I/R injury caused by transient
      clamping of the infrarenal aorta led to a time-dependent increase of all measured
      cytokines except IL-4, IL-5, and granulocyte macrophage-colony stimulating
      factor. This was accompanied by elevated markers of organ damage (ALT, AST, and
      LDH) except creatinine. Preconditioning with Pam(3)CSK(4) led to lower plasma
      concentrations of all cytokines, with the exception of anti-inflammatory IL-10
      which was significantly upregulated. Furthermore, ALT, AST, and LDH plasma
      concentrations were lower in the preconditioning group. TLR2-deficient mice
      similarly showed reduced signs of systemic inflammation and organ damage,
      although less distinctive. IL-2, IL-6, IL-12, ALT, and LDH were time dependently
      lower compared with WT mice. IL-10 concentration was higher in TLR2-deficient
      mice compared with WT. CONCLUSIONS: Both, preconditioning via TLR2 and TLR2
      deficiency, ameliorate systemic inflammation and organ damage during I/R injury
      caused by clamping of the infrarenal aorta. Compared with untreated WT animals,
      Pam(3)CSK(4) preconditioned and TLR2-deficient mice showed lower concentrations
      of pro-inflammatory cytokines, whereas anti-inflammatory IL-10 was elevated in
      both groups. This was accompanied by reduced organ dysfunction parameters.

PMID- 22622112
TI  - Maintenance treatment with inhaled ampicillin in patients with cystic fibrosis
      and lung infection due to methicillin-sensitive Staphylococcus aureus.

PMID- 22622113
TI  - [Fragile XX: the women's heart].

PMID- 22622114
TI  - [Preface. Presence of women in scientific research].

PMID- 22622115
TI  - [Sex and gender medicine: how women's heart is vulnerable].

PMID- 22622116
TI  - [Genetic basis of ischemic heart disease. Do women have distinctive
      characteristics?].
AB  - More women die every year from cardiovascular disease than men from any other
      cause. Several fundamental variations have been reported in the mechanisms
      underlying coronary artery disease, which suggest that its genetic basis varies
      by gender. Such differences are not limited to gonadal hormones and can be seen
      in the physiology of atherosclerosis, including plaque components, endothelial
      function and hemostasis. It is possible to speculate that genetic factors are
      different in men and women and probably involve biological pathways that have not
      yet been identified. To date, studies performed by means of the candidate gene
      approach have identified several genetic variants associated with coronary artery
      disease in women. However, these scientific data have not been translated into
      clinical practice. It has recently become possible to search for common gene
      variants that affect the susceptibility to myocardial infarction on the basis of
      our knowledge of common single nucleotide polymorphisms and haplotypes across the
      human genome using genome-wide genotyping technologies. Currently more than 20
      gene regions have been associated with ischemic heart disease using this
      approach. However, so far we do not know several genetic variants differently
      associated with risk of ischemic heart disease in men and women. A challenge for
      the near future will therefore be to identify genetic variants that maximally
      differentiate males from females, and also to identify possible relationships
      between genes and environment and genes and hormones in both sexes.

PMID- 22622117
TI  - [Pathophysiology of ischemic heart disease in women].
AB  - Ischemic heart disease (IHD) is the leading cause of death in women as in men.
      Several disease mechanisms, however, differ between genders. Women with IHD more
      frequently than men have normal or non-obstructive epicardial arteries, plaque
      erosion, spontaneous coronary dissection, microvascular dysfunction, stress
      cardiomyopathy, and heart rupture after acute infarction. Compared to men, IHD
      presents 7-10 years later with a heavier burden of cardiovascular risk factors,
      even after correction for age. The typical woman with IHD is old and frail, with
      comorbidities such as renal failure. Another vulnerable group comprises those
      with acute coronary syndromes before the age of 60 in whom hospital mortality is
      reported to be almost twice that of age-matched men. Such vulnerabilities in
      women, in apparent contrast with the delayed onset and lesser extent of
      epicardial atherosclerosis, may be attributable to biases in prevention,
      presentation, diagnosis and treatment of female IHD, but also to gender-related
      differences in disease mechanisms.

PMID- 22622118
TI  - [Is menopause a risk factor for ischemic heart disease in women?].
AB  - Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in
      men and women worldwide. The apparent cardioprotective effects of endogenous
      estrogens seem to prevent CVD in premenopausal women. Following menopause and
      loss of hormonal effects, gender-based differences in CVD are reduced, with the
      CVD risk being higher in women who develop the metabolic syndrome. In
      postmenopausal women, many features of the metabolic syndrome emerge with
      estrogen deficiency. Estrogen deficiency occurring in the menopausal period is
      associated with 1) dyslipidemia (hypertriglyceridemia, reduced HDL, and increased
      small dense LDL particles); 2) insulin resistance; 3) hypertension; 4) increased
      central fat and reduction in lean body mass; and 5) increased hypercoagulability
      and pro-inflammatory state. In addition to traditional cardiovascular risk
      factors, also early menopause has a negative impact on females. Over the past
      years, different approaches were found to improve quality of life and
      cardiovascular health in menopausal women. Since the concept of hormone
      replacement therapy (HRT), large observational studies and randomized clinical
      trials have amassed a wealth of data about the effects of menopause and the
      safety and efficacy of using estrogen replacement therapies to treat menopause
      symptoms and menopause-related diseases. While there is no question that HRT
      effectively mitigates troublesome menopause symptoms, conflicting evidence about
      other effects of HRT has fueled controversy concerning its relative benefits and
      risks. Moreover, it seems that CVD protection mediated by replacement therapy is
      maximum when treatment is initiated in the absence of signs of atherosclerosis
      (typically in the premenopausal period), whereas it vanishes as atherosclerosis
      progresses (postmenopausal period). However, many questions remain unsolved
      regarding the effectiveness of hormonal compounds, doses, regimens, and route of
      administration. On the basis of these considerations, it is necessary in the near
      future to expand scientific knowledge and develop appropriate lifestyle
      modifications and therapeutic strategies for the treatment of either traditional
      cardiovascular risk factors or menopause-related metabolic changes.

PMID- 22622119
TI  - [Antithrombotic drugs in women: should we worry more about bleeding?].
AB  - Since the mid '90s, the concept of evidence-based medicine has grown
      exponentially, contributing to the advancement of personalized medicine, which
      considers the "female gender" as an extremely important area of customization,
      but orphan of targeted research. Strong evidence do exists demonstrating gender
      differences in bleeding risk associated with antithrombotic treatment, mostly
      related to lower values of body mass, organ size and renal function in women than
      men. Across clinical studies, the search for the specific risk of bleeding in the
      female vs male gender has gained attention only recently; therefore, data from
      different studies and relatively limited meta-analyses should be assessed
      carefully. As for antiplatelet therapy for primary prevention, the risk of major
      bleeding events, such as cerebral hemorrhage, is lower for women than for men.
      Conversely, in acute situations in which antithrombotic drugs are given in
      association, the risk of bleeding is greater for women, in particular for
      combination therapies with heparin or low molecular weight heparin or
      thrombolytic agents. Numerous studies in the literature evaluated the incidence
      of minor and major bleeding during oral anticoagulant therapy in relation to
      gender, but the results are not entirely consistent and appear to vary over the
      years. In summary, there are some aspects of guidance in the complex spectrum of
      the bleeding risk related to antithrombotic treatment, with indications of a
      lower bleeding risk in women than men related to long-term preventive single
      antithrombotic drug treatments. In addition, hormonal effects and use of
      outprescribed drugs may also play a significant role in modulating hemostasis.

PMID- 22622120
TI  - [Does percutaneous coronary intervention in women provide the same results as in
      men?].
AB  - Ischemic heart disease shows gender differences, both in terms of clinical
      characteristics and pathophysiological mechanisms. It is still debated whether
      these characteristics influence the diagnostic and therapeutic approach and the
      outcomes in female patients treated with percutaneous coronary intervention.
      Percutaneous coronary intervention in women has been shown to be feasible, safe
      and effective as it is in men throughout the whole clinical spectrum of ischemic
      syndromes. There is a solid scientific evidence of a different diagnostic and
      therapeutic approach to women suffering from ischemic heart disease compared to
      men, with a tendency to undertreat female patients, despite the worst risk
      profile at presentation. Women, in fact, less frequently undergo coronary
      angiography and receive antiplatelet, antithrombotic or anti-ischemic drugs. They
      experience more bleedings than men after administration of glycoprotein IIb/IIIa
      inhibitors. Gender differences, therefore, affect more the clinical than the
      interventional approach. At least in part, this is due to the fact that current
      guidelines are based on a male model of diagnostics. It would be desirable to
      analyze cohorts of patients in whom the percentage of individuals of both sexes
      will be equally represented, or rather, exclusively female cohorts in order to
      formulate more targeted diagnostic and therapeutic indications.

PMID- 22622121
TI  - [Does cardiac surgery in women carry a higher risk than in men?].
AB  - Cardiovascular diseases are the leading cause of death in women, and female
      patients exhibit peculiar features as to symptoms, diagnosis and treatment. This
      sex difference is also observed in cardiac surgery, with mortality and morbidity
      being higher in female patients. Whether female gender is an independent variable
      for mortality still remains controversial. This review summarizes the data
      available in the literature on cardiac surgery in the female population.

PMID- 22622122
TI  - [Gender effect on cardiomyopathy].
AB  - The role of a gender effect (that means differences in clinical manifestations,
      access to therapies and response to treatments according to gender) in
      cardiomyopathies remains a matter of debate. Although recent studies have
      evaluated the differences in the clinical features and prognosis between the two
      sexes, many issues remain to be elucidated. At present, the only sex-specific
      condition that affects females is peripartum cardiomyopathy. Recent evidence
      suggests a pathogenetic role of a prolactin derivative, and ongoing clinical
      trials are investigating the possibility of targeted therapies using prolactin
      secretion inhibitors, such as bromocriptine and carbegoline. Although women were
      considered so far only carriers of X-linked diseases (Anderson-Fabry disease,
      Danon disease, Hunter syndrome and dystrophinopathies), clinical experience
      showed a wide spectrum of clinical manifestations in females due to random X
      chromosome inactivation. Conversely, in mitochondrial diseases (with matrilineal
      inheritance), cardiomyopathies may occur in the context of clinical multisystemic
      involvement without significant gender-related differences. Autosomal inherited
      cardiomyopathies also show different phenotypes and prognostic impact according
      to gender. The hypothesis of a premenopausal protective role of female hormones
      towards myocardial involvement has been raised by recent data on transtiretin
      related amyloidosis and hypertrophic cardiomyopathy. Preexisting cardiomyopathies
      may affect pregnancy, labor and delivery in women, since all these conditions are
      associated with important hemodynamic changes. Women with low-risk hypertrophic
      cardiomyopathy (asymptomatic and without left ventricular outflow tract gradient)
      usually can tolerate pregnancy. Conversely, women who are symptomatic before
      pregnancy or have severe hypertrophy with important outflow tract gradient are at
      higher risk and should be referred to a tertiary center to be evaluated on a case
      by case basis. Pregnancy in women with dilated cardiomyopathy and significant
      left ventricular systolic dysfunction represents a high-risk condition. In
      addition, information on the clinical course and potential complications in
      pregnant women with arrhythmogenic right ventricular cardiomyopathy or
      restrictive cardiomyopathy is limited to individual reports.

PMID- 22622123
TI  - [Sudden cardiac death in women].
AB  - Although the incidence of sudden cardiac death (SCD) is greater in men than in
      women, it represents an important mode of death also in the female gender. Sex
      related differences have been identified not only in the prevalence of the
      phenomenon, but also in risk factors and etiology of SCD. The peripartum period
      represents a peculiar trigger of SCD in women with underlying cardiovascular
      substrates. Several lesions, both congenital and acquired, may be identified at
      postmortem in SCD victims, including coronary artery, myocardial, valve, and
      aortic diseases. While the incidence of SCD increases progressively with age in
      adult elderly women to reach a 1:1 male:female ratio after the age of 80 years,
      mostly due to the increasing incidence of atherosclerotic disease in the
      postmenopausal period, SCD in young women is a rare event and usually associated
      with non-atherosclerotic disease, such as mitral valve prolapse, spontaneous
      coronary dissection, myocarditis, inherited cardiomyopathies and congenital heart
      diseases. The heart can be found structurally normal and inherited ion channel
      diseases are often implicated. Gender differences in the risk of SCD deserve
      further attention, since they affect the evaluation of interventions designed to
      reduce the rate of female SCD.

PMID- 22622124
TI  - [Does a woman's heart beat faster?].
AB  - Recent publications have identified a different epidemiological prevalence
      related to sex in some of the most common supraventricular and ventricular
      arrhythmias. This fact is attributed to the effect of sex hormones on myocardial
      cell electrophysiology. Women, in particular, have a higher prevalence than males
      with regard to intranodal reentrant tachycardia, idiopathic monomorphic
      ventricular tachycardia and ventricular arrhythmias in congenital or acquired
      long QT syndrome. A higher incidence in females with regard to complications
      during atrial fibrillation has also been reported. This paper examines data from
      the literature regarding gender differences in the prevalence of the most common
      arrhythmias, the causes of these differences, and some discriminating aspects
      related to female sex in the architecture of published clinical studies.

PMID- 22622125
TI  - [Female gender and pulmonary arterial hypertension: a complex relationship].
AB  - Pulmonary arterial hypertension (PAH) is a severe clinical condition defined as
      mean pulmonary artery pressure >=25 mmHg and normal pulmonary capillary wedge
      pressure (<=15 mmHg). In PAH the increase in pulmonary pressure is due to an
      intrinsic disease of the small pulmonary arteries (resistance vessels)
      characterized by vascular proliferation and remodeling. The increase in pulmonary
      vascular resistance with subsequent elevation of the right ventricular afterload
      leads to right ventricular failure after variable periods of time. Although
      targeted disease therapies have been developed over the last decade that resulted
      in improved quality of life and outcome for PAH patients, the prognosis is still
      severe and there remains no cure for this disease. From a clinical standpoint,
      PAH includes a group of heterogeneous pathological conditions: in idiopathic,
      heritable and drug- and toxin-induced PAH, since there are no predisposing
      clinical conditions, the structural changes in pulmonary circulation are
      "isolated"; on the other hand, PAH may be associated with some predisposing
      diseases such as connective tissue disease, HIV infection, portal hypertension,
      congenital heart disease, schistosomiasis, and chronic hemolytic anemia. PAH can
      affect individuals of all age groups, and mean age at diagnosis is around 50
      years. Epidemiological data show a great preponderance of females in PAH; the
      high prevalence of females is particularly evident in the so-called "isolated"
      PAH forms, whereas in PAH associated with other diseases the female:male ratio is
      strongly influenced by the epidemiological features of the specific predisposing
      condition. The reason for the higher female prevalence in PAH has never been
      clarified: some hypotheses involve the role of sexual hormones (estrogens),
      autoimmunity, or an X-linked locus in disease predisposition. Female gender is
      not associated with a different clinical presentation. However, the age of onset
      tends to be earlier in females than in males. As far as prognosis is concerned,
      male patients are at greater risk of mortality despite similar therapeutic
      management: this could be linked to the influence of sexual hormones, which may
      favor disease development but may also have favorable effects on outcome,
      especially on treatment response (the "estrogen paradox"). The possibility that
      female sex hormones may influence the development and clinical expression of PAH
      is underlined by the frequent onset of PAH during pregnancy or shortly after
      delivery, and by the description of obligate carriers of heritable PAH (BMPR2
      mutation carriers) in whom hormone replacement therapy seems to trigger the
      manifestation of the disease. Nevertheless, a definite pathobiological mechanism
      to explain the association between female sex hormones and PAH has yet to be
      identified. The link between pregnancy and PAH is also uncertain. However, the
      hemodynamic changes that occur during gestation, and mainly during labor and
      delivery, are poorly tolerated by PAH patients: this is reflected in the timing
      of clinical deterioration and the increased mortality in the late stages of
      pregnancy when maximum increase in blood volume and cardiac output occurs. As
      such, the current clinical recommendation is that pregnancy should strongly be
      discouraged and if it occurs, early termination is advised. When PAH is not
      diagnosed until late in pregnancy, close follow-up of the mother is mandatory and
      elective planned delivery is recommended: care of pregnant women with PAH
      requires a highly planned, multidisciplinary approach, involving obstetricians,
      pulmonary hypertension specialists, anesthesiologists and intensivists,
      preferably in a dedicated PAH referral center. Use of female hormones for birth
      control and postmenopausal replacement therapy in PAH patients still remains
      controversial; in fact, although it has been suspected to be a trigger factor for
      PAH development, a formal association based on case-control studies has not been
      documented.

PMID- 22622126
TI  - [Cardioprotection in women with neoplastic disease].
AB  - Cardiotoxicity (CTX) is a serious adverse effect of anticancer drugs that impacts
      on quality of life and overall survival of cancer patients. Hypokinetic
      cardiomyopathy is the most typical form of CTX, and it is traditionally
      considered refractory to therapy. Prevention of CTX remains of paramount
      importance, and several measures, including serial cardiac function monitoring,
      reduction of cumulative anthracycline dose, use of anthracycline analogues and
      cardioprotective agents, have been proposed. Over the last decade, however, a new
      approach based on cardiac biomarkers has emerged as an effective alternative
      strategy for the early detection of subclinical cardiac injury. In particular,
      the role of troponin I in identifying patients at risk of CTX as well as of
      angiotensin-converting enzyme inhibitors in preventing left ventricular
      dysfunction and late cardiac events in high-risk patients, namely those with
      raised troponin I levels after chemotherapy, has been consistently demonstrated
      as an effective tool for CTX prevention.

PMID- 22622127
TI  - Recessive deoxyguanosine kinase deficiency causes juvenile onset mitochondrial
      myopathy.
AB  - Deoxyguanosine kinase (DGUOK) (MIM#601465) deficiency was originally described as
      the cause of an infantile onset hepatocerebral mitochondrial disease [1]. The
      classic features of this disorder include significant hepatic failure with
      nystagmus and hypotonia. Mitochondrial DNA studies reveal significant
      mitochondrial DNA depletion in the affected tissues. Subsequently it has been
      shown that the same mutations in this gene may present with isolated acute liver
      failure without cerebral involvement. In this paper we studied the mitochondrial
      DNA depletion in cells from a patient presenting with mitochondrial myopathy
      caused by a novel mutation in DGUOK. Subsequently we developed the method to
      diagnose this condition using MyoD induced fibroblasts to study the muscle
      specific phenotype. In addition, supplementation of MyoD induced fibroblasts with
      dAMP and dGMP resulted in a restoration of mtDNA quantity.

PMID- 22622128
TI  - Low Temperature Plasma for decontamination of E. coli in milk.
AB  - Raw milk is a natural, highly nutritious product and a quick and easy supplement
      for human dietary requirements. Elimination of bacteria in milk has been a
      problem for decades and new methods with regards to non-thermal applications
      which do not harm the chemical composition of milk, are currently under
      investigation. The objective of the study was to determine the potential use of a
      novel, Low Temperature Plasma (LTP) system for its capability of killing
      Escherichia coli in milk with different fat contents. The time dependent effect
      of atmospheric corona discharge generated with 9kV of AC power supply on E. coli
      ATCC 25922 dispersed in whole, semi skimmed and skimmed milk was examined. Plasma
      was applied at time intervals of 0, 3, 6, 9, 12, 15 and 20min. A significant 54%
      reduction in the population of E. coli cells after only 3min was observed
      regardless of the fat content of the milk. The initial pre-plasma bacterial count
      of 7.78 Log CFU/ml in whole milk was decreased to 3.63 Log CFU/ml after 20min of
      plasma application. LTP did not cause any significant change to the pH and color
      values of raw milk samples. No viable cells were detected after one week
      examination in whole milk samples and remained so over the 6week storage period.
      The findings of this study show that the novel LTP system tested was able to
      significantly reduce E. coli in milk by more than a 3 fold log reduction without
      significantly affecting pH or color properties.

PMID- 22622129
TI  - A quantitative TR-FRET plate reader immunoassay for measuring autophagy.
AB  - Autophagy involves the isolation and targeting of unwanted cellular components to
      lysosomes for their digestion and reuse. Autophagic dysregulation has recently
      been implicated in a wide range of disease processes, yet facile methods for
      quantifying autophagy have been lacking in the field. Here we describe the
      generation of a quantitative plate reader assay for measuring the autophagic
      activity of cells. One of the best characterized autophagy markers is the protein
      LC3B, which normally resides in the cytosol (LC3B-I) but upon induction of
      autophagy becomes lipidated and embedded in autophagosomal membranes (LC3B-II).
      To quantify autophagy, we reasoned that GFP-tagged LC3B could serve as a time
      resolved fluorescence resonance energy transfer (TR-FRET) acceptor upon cell
      lysis in the presence of terbium-labeled LC3B antibodies. Using this TR-FRET
      immunoassay approach, we screened a panel of LC3B antibodies and identified an
      antibody that exhibits strong preferential affinity toward autophagosome
      associated LC3B-II and thereby facilitates specific detection of autophagic
      activity. The plate reader format provides both a quantitative and an objective
      result, thus overcoming some of the key limitations of the traditional
      immunoblotting and imaging approaches used to monitor autophagy. Moreover, since
      the assay step requires only a single addition of cell lysis buffer containing
      the detection antibody its simple workflow is both automation-friendly and
      scalable, which renders it suitable for high-throughput screening. We demonstrate
      how this TR-FRET immunoassay for GFP-tagged LC3B-II can be applied to
      quantitatively detect changes in the autophagy activity of cells, including
      estimating effects on autophagic flux.

PMID- 22622130
TI  - Ileocolic intussusception due to giant ileal lipoma: Review of literature and
      report of a case.
AB  - INTRODUCTION: Intussusception in adults accounts for less than 5% of all
      intussusceptions. It occurs when a segment of intestine invaginates into itself.
      PRESENTATION OF A CASE: We report a case of ileocolic intussusception in an adult
      caused by a giant ileal lipoma. DISCUSSION: Intussusceptions can be classified as
      ileocolic, ileocecal, colo-colic and ileo-ileal. Most are due to neoplasms (60%
      malign and 24-40% benign). In the colon, the possibility of malignancy is higher
      than in small intestine. Lipomas are the most common benign mesenchymal
      intestinal tumors, accounting for less than 5% of all gastrointestinal tumors.
      They are more frequent in colon than small intestine. Small lipomas (less than
      2cm) are usually asymptomatic. Larger lesions may produce symptoms such as
      abdominal pain, obstruction or intussusception. Lipomas can be diagnosed with
      endoscopy, capsule endoscopy, barium enemas, CT and US. CONCLUSION:
      Intussusceptions in adults is a rare condition, most of them are caused by a
      malign neoplasms followed by benign neoplasms. US and CT are useful for
      diagnosis. Surgery is mandatory.

PMID- 22622131
TI  - Impaired mitochondrial biogenesis contributes to depletion of functional
      mitochondria in chronic MPP+ toxicity: dual roles for ERK1/2.
AB  - The regulation of mitochondrial quality has emerged as a central issue in
      neurodegeneration, diabetes, and cancer. We utilized repeated low-dose
      applications of the complex I inhibitor 1-methyl-4-phenylpyridinium (MPP(+)) over
      2 weeks to study cellular responses to chronic mitochondrial stress. Chronic
      MPP(+) triggered depletion of functional mitochondria resulting in diminished
      capacities for aerobic respiration. Inhibiting autophagy/mitophagy only partially
      restored mitochondrial content. In contrast, inhibiting activation of
      extracellular signal-regulated protein kinases conferred complete cytoprotection
      with full restoration of mitochondrial functional and morphological parameters,
      enhancing spare respiratory capacity in MPP(+) co-treated cells above that of
      control cells. Reversal of mitochondrial injury occurred when U0126 was added 1
      week after MPP(+), implicating enhanced repair mechanisms. Chronic MPP(+) caused
      a >90% decrease in complex I subunits, along with decreases in complex III and IV
      subunits. Decreases in respiratory complex subunits were reversed by co-treatment
      with U0126, ERK1/2 RNAi or transfection of dominant-negative MEK1, but only
      partially restored by degradation inhibitors. Chronic MPP(+) also suppressed the
      de novo synthesis of mitochondrial DNA-encoded proteins, accompanied by decreased
      expression of the mitochondrial transcription factor TFAM. U0126 completely
      reversed each of these deficits in mitochondrial translation and protein
      expression. These data indicate a key, limiting role for mitochondrial biogenesis
      in determining the outcome of injuries associated with elevated mitophagy.

PMID- 22622132
TI  - Preferential Fas-mediated apoptotic execution at G1 phase: the resistance of
      mitotic cells to the cell death.
AB  - Apoptosis is induced by various stresses generated from the extracellular and
      intracellular environments. The fidelity of the cell cycle is monitored by
      surveillance mechanisms that arrest its further progression if any crucial
      process has not been completed or damages are sustained, and then the cells with
      problems undergo apoptosis. Although the molecular mechanisms involved in the
      regulation of the cell cycle and that of apoptosis have been elucidated, the
      links between them are not clear, especially that between cell cycle and death
      receptor-mediated apoptosis. By using the HeLa.S-Fucci (fluorescent
      ubiquitination-based cell cycle indicator) cells, we investigated the
      relationship between the cell cycle progression and apoptotic execution. To
      monitor apoptotic execution during cell cycle progression, we observed the cells
      after induction of apoptosis with time-lapse fluorescent microscopy. About 70% of
      Fas-mediated apoptotic cells were present at G(1) phase and about 20% of cells
      died immediately after cytokinesis, whereas more than 60% of etoposide-induced
      apoptotic cells were at S/G(2) phases in random culture of the cells. These
      results were confirmed by using synchronized culture of the cells. Furthermore,
      mitotic cells showed the resistance to Fas-mediated apoptosis. In conclusion,
      these findings suggest that apoptotic execution is dependent on cell cycle phase
      and Fas-mediated apoptosis preferentially occurs at G(1) phase.

PMID- 22622133
TI  - In vitro differentiation of mouse embryonic stem cells into inner ear hair cell
      like cells using stromal cell conditioned medium.
AB  - Hearing loss is mainly caused by loss of sensory hair cells (HCs) in the organ of
      Corti or cochlea. Although embryonic stem (ES) cells are a promising source for
      cell therapy, little is known about the efficient generation of HC-like cells
      from ES cells. In the present study, we developed a single-medium culture method
      for growing embryoid bodies (EBs), in which conditioned medium (CM) from cultures
      of ST2 stromal cells (ST2-CM) was used for 14-day cultures of 4-day EBs. At the
      end of the 14-day cultures, up to 20% of the cells in EB outgrowths expressed HC
      related markers, including Math1 (also known as Atoh1), myosin6, myosin7a,
      calretinin, alpha9AchR and Brn3c (also known as Pou4f3), and also showed
      formation of stereocilia-like structures. Further, we found that these cells were
      incorporated into the developing inner ear after transplantation into chick
      embryos. The present inner ear HC induction method using ST2-CM (HIST2 method) is
      quite simple and highly efficient to obtain ES-derived HC-like cells with a
      relatively short cultivation time.

PMID- 22622134
TI  - A new layered metal-organic framework as a promising heterogeneous catalyst for
      olefin epoxidation reactions.
AB  - A new layered MOF material [Co(Hoba)(2).2H(2)O] (1) (H(2)oba = 4,4'
      oxybis(benzoic acid)) has been synthesized and used as a highly recyclable
      heterogeneous catalyst for olefin epoxidation reactions. Both high conversion
      (96%) and high selectivity of epoxide products (96%) are achieved.

PMID- 22622136
TI  - Psychopaths and posttraumatic stress.

PMID- 22622137
TI  - Two distinct electrocardiographic forms of idiopathic ventricular arrhythmia
      originating in the vicinity of the His bundle.
AB  - AIM: The objective is to assess electrocardiographic characteristics predicting
      the precise location of ventricular arrhythmia (VA) origin within the right
      ventricle (RV) close to the His bundle (HB) region. METHODS AND RESULTS: Twenty
      five patients (14 men, age 65 +/- 14 years) underwent successful catheter
      ablation of para-Hisian VA. Ventricular arrhythmias were considered to arise in
      the vicinity of the HB region based on the criteria that mapping exhibited the
      earliest RV activation before QRS onset in the HB region. Surface 12-lead
      electrocardiogram during the para-Hisian VAs was analysed. Of the 25 patients, 8
      originated from the RV antero-septum just above the HB region, and 17 arose from
      the RV mid-septum just below the HB region. There was no significant difference
      in precedence of the local ventricular electrogram of the HB region from the
      onset of surface QRS during VAs. Surface electrocardiographic findings were
      characterized according to R-wave amplitude in lead I (0.43 +/- 0.18 vs. 0.67 +/-
      0.19 mV, P = 0.005), mean R-wave amplitude in inferior leads (1.12 +/- 0.32 vs.
      0.71 +/- 0.24 mV, P = 0.002), R-wave amplitude ratio of leads III/II (0.77 +/-
      0.10 vs. 0.50 +/- 0.23, P = 0.005), incidence of S-wave in lead III [1/8 (13%)
      vs. 16/17 (94%), P < 0.001], and QS morphology in lead V1 [3/8 (38%) vs. 17/17
      (100%), P = 0.001]. CONCLUSIONS: Despite their adjacent locations, para-Hisian
      VAs could be classified into two subgroups with distinctive electrocardiographic
      characteristics according to origin either above or below the HB region. The
      present findings can be helpful for planning catheter ablation of para-Hisian
      VAs, and can reduce the risk of inadvertent atrioventricular block.

PMID- 22622135
TI  - Cellular mechanisms of gamma-secretase substrate selection, processing and
      toxicity.
AB  - Presenilins (PSs) are catalytic components of the gamma-secretase proteolytic
      complexes that produce Abeta and cell signaling peptides. gamma-Secretase
      substrates are mostly membrane-bound peptides derived following proteolytic
      cleavage of the extracellular domain of type I transmembrane proteins. Recent
      work reveals that gamma-secretase substrate processing is regulated by proteins
      termed gamma-secretase substrate recruiting factors (gammaSSRFs) that bridge
      substrates to gamma-secretase complexes. These factors constitute novel targets
      for pharmacological control of specific gamma-secretase products, such as Abeta
      and signaling peptides. PS familial Alzheimer's disease (FAD) mutants cause a
      loss of gamma-secretase cleavage function at epsilon sites of substrates thus
      inhibiting production of cell signaling peptides while promoting accumulation of
      uncleaved toxic substrates. Importantly, gamma-secretase inhibitors may cause
      toxicity in vivo by similar mechanisms. Here we review novel mechanisms that
      control gamma-secretase substrate selection and cleavage and examine their
      relevance to AD.

PMID- 22622139
TI  - Atrial fibrillation and fibrosis: role of connective tissue growth factor.

PMID- 22622138
TI  - Type III procollagen-N-peptide as a predictor of persistent atrial fibrillation
      recurrence after cardioversion.
AB  - AIMS: Fibrosis and inflammation may play a significant role in the pathogenesis
      of atrial fibrillation (AF) recurrence. Type III procollagen-N-peptide (PIIINP)
      may be related to atrial fibrosis and play a role in predicting the recurrence of
      AF. We investigated whether PIIINP as a fibrosis marker predicts the recurrence
      of AF after cardioversion. METHODS AND RESULTS: Serum PIIINP, interleukin-6, high
      sensitivity C-reactive protein, brain natriuretic peptide, renin and aldosterone
      were measured at baseline and 24 months in 88 patients (62%) with sinus rhythm
      (SR) maintenance and 54 patients (38%) with AF recurrence. Furthermore, the root
      mean square voltage in the last 20 ms (RMS20) via P-wave signal-averaged
      electrocardiogram (P-SAECG) was measured and the relationship between fibrosis
      biomarkers and RMS20 was examined. Baseline PIIINP with AF recurrence was
      significantly higher than for those with SR maintenance (0.664 vs. 0.581 U/mL, P
      = 0.001). However, there were no significant differences in other biomarkers. A
      logistic regression identified PIIINP (odds ratio 2.61, P = 0.008) as an
      independent predictor of AF recurrence. The RMS20 as measured by P-SAECG with SR
      maintenance and PIIINP levels <0.72 U/mL (at baseline) was significantly higher
      after 24 months than at baseline. Furthermore, the RMS20 with AF recurrence and
      PIIINP levels >0.72 U/mL (at baseline) was significantly lower after 24 months
      than baseline. CONCLUSIONS: Elevated baseline PIIINP concentration is an
      independent predictor for AF recurrence after cardioversion. Furthermore, there
      is a relationship between PIIINP and RMS20 and the fibrosis of AF.

PMID- 22622140
TI  - Recurrent unilateral pleural effusion in a hypertrophic cardiomyopathy patient
      secondary to atrial arrhythmias and the role of radiofrequency ablation.
AB  - Heart failure (HF) is a common cause of pleural effusion. Atrial tachyarrhythmias
      (ATa) can precipitate HF. ATa precipitating unilateral pleural effusion (PLE) has
      not been reported. We report a case of ATa in a patient with hypertrophic
      cardiomyopathy with recurrent unilateral rightsided PLE and resolution of
      effusion with catheter ablation of the arrhythmia.

PMID- 22622141
TI  - Adenosine plus dipyridamole: a novel strategy to enhance adenosine-induced
      conduction recovery after pulmonary vein isolation.
AB  - AIMS: Intravenous administration of adenosine after a pulmonary vein (PV)
      isolation procedure can unmask residual, so-called 'dormant', conduction that
      would otherwise remain unnoticed. Elimination of these dormant potentials is
      challenging because of the transient effect of adenosine, often requiring
      repeated injections. We tested the hypothesis that dipyridamole, a drug which
      inhibits adenosine deamination, can provoke longer-lasting unmasking of dormant
      conduction. METHODS AND RESULTS: In 191 patients with drug refractory paroxysmal
      atrial fibrillation, a bolus of 12-24 mg of adenosine was administered after all
      764 PVs were isolated. In the case of transient dormant conduction, a short
      infusion of dipyridamole 50 mg was given and a bolus of adenosine was repeated.
      In all cases, re-isolation was attempted guided by the activation pattern in the
      PV on a circular mapping catheter. Duration of adenosine-induced dormant
      conduction before and after dipyridamole was recorded as the time between
      administration of adenosine and cessation of dormant conduction either
      spontaneously or by catheter ablation. Transient dormant conduction was re
      established by a single bolus of adenosine in 24 of 191 patients (12.6%). Mean
      duration of adenosine-induced dormant conduction before dipyridamole was 13.1 +/-
      6.4 s, whereas it was significantly longer at 218.9 +/- 165.6 s after
      dipyridamole (P < 0.0001). Eighteen of the 24 PVs were re-isolated by catheter
      ablation before spontaneous cessation of dormant conduction, and in 6 cases
      dormant conduction disappeared spontaneously before PV re-isolation was achieved.
      CONCLUSION: Dipyridamole significantly prolongs the effect of adenosine to unmask
      dormant conduction after PV isolation and may thus facilitate its elimination by
      catheter ablation.

PMID- 22622142
TI  - Reprogramming of human fibroblasts into multipotent cells with a single ECM
      proteoglycan, fibromodulin.
AB  - Pluripotent and/or multipotent stem cell-based therapeutics are a vital component
      of tissue engineering and regenerative medicine. The generation or isolation of
      safer and readily available stem cell sources will significantly aid clinical
      applications. We report here a technique using a single molecule, recombinant
      human fibromodulin protein (FMOD), to reprogram human fibroblasts into
      multipotent cells. Like virally-induced pluripotent stem (iPS) cells, FMOD
      reprogrammed (FReP) cells express pluripotency markers, form embryoid bodies
      (EBs), and differentiate into ectoderm, mesoderm, and endoderm derivatives in
      vitro. Notably, FReP cells regenerate muscle and bone tissues but do not generate
      teratomas in vivo. Unlike iPS cells, undifferentiated FReP cells proliferate
      slowly and express low proto-oncogene c-MYC and unexpectedly high levels of
      cyclin-dependent kinase inhibitors p15(Ink4B) and p21(WAF1/Cip1). Remarkably, in
      a fashion reminiscent of quiescent stem cells, the slow replicative phenotype of
      undifferentiated FReP cells reverses after differentiation induction, with
      differentiating FReP cells proliferating faster and expressing less p15(Ink4B)
      and p21(WAF1/Cip1) than differentiating iPS cells. Overall, single protein, FMOD
      based, cell reprograming bypasses the risks of mutation, gene instability, and
      malignancy associated with genetically-modified iPS cells, and provides an
      alternative strategy for engineering patient-specific multipotent cells for basic
      research and therapeutic application.

PMID- 22622143
TI  - Management of chronic neuropathic pain following mandibular advancement surgery.
AB  - This report highlights the management of a rare complication, namely allodynia,
      which arose following mandibular advancement surgery. A 56-year-old female
      underwent bilateral sagittal ramus advancement osteotomy. Postoperatively, she
      developed allodynia corresponding to the distribution of the left inferior
      alveolar nerve. A hierarchical pathway of topical and pharmacological agents
      followed by ablative techniques was used without success. Eventually, electrical
      neuromodulation via a motor cortex stimulator was implemented to manage the
      symptoms. The report serves to outline treatment options available and the risks
      associated with this treatment.

PMID- 22622144
TI  - Chlorhexidine for the prevention of alveolar osteitis.
AB  - This systematic review assessed the efficacy of chlorhexidine for the prevention
      of alveolar osteitis and occurrence of adverse reactions. Databases were searched
      until 20 April 2011. Trial inclusion criteria were: titles/abstracts relevant to
      topic; prospective 2-arm (or more) clinical study design. Trial exclusion
      criteria were: not all entered subjects accounted for; subjects of both groups
      not followed up the same way; lack of computable data; chlorhexidine not the
      primary test agent; duplication of data; outcome of interest other than incidence
      of alveolar osteitis. Individual datasets were extracted from accepted articles.
      Bias risk in trials was assessed. 10 of 13 included trials were accepted. From
      these, 16 dichotomous datasets were extracted. Two of six application protocols
      favoured chlorhexidine over placebo: Single application of 0.2% chlorhexidine gel
      placed in the socket immediately after extraction versus placebo gel (RR 0.40;
      95% CI: 0.18-0.90; p=0.03) and 0.12% chlorhexidine rinse applied on day of
      surgery and used twice daily for 7 days postoperatively versus placebo rinse (RR
      0.50; 95% CI: 0.27-0.93; p=0.03). These results are negated due to high bias
      risk. Chlorhexidine did not cause higher adverse reactions than placebo. Further
      high-quality randomised control trials are needed.

PMID- 22622145
TI  - Structural basis for oxygen sensing and signal transduction of the heme-based
      sensor protein Aer2 from Pseudomonas aeruginosa.
AB  - The crystal structure of a truncated Aer2, a signal transducer protein from
      Pseudomonas aeruginosa, consisting of the heme-containing PAS and di-HAMP domains
      revealed that a distal tryptophan residue (Trp283) plays an important role in
      stabilizing the heme-bound O(2) and intra-molecular signal transduction upon O(2)
      binding.

PMID- 22622146
TI  - Is renal thrombotic angiopathy an emerging problem in the treatment of ovarian
      cancer recurrences?
AB  - BACKGROUND AND OBJECTIVE: Ovarian cancer is usually diagnosed at an advanced
      stage, with most patients undergoing surgery followed by platinum- and taxane
      based chemotherapy. After initial clinical remission, the majority recur, leading
      to additional treatments, including not only platinums and taxanes but also
      pegylated liposomal doxorubicin (PLD), gemcitabine, topotecan, and, more
      recently, bevacizumab, which may extend survival times. PLD, in particular, has
      been extensively studied by our group, with encouraging therapeutic results. We,
      however, observed instances of chronic kidney disease (CKD) developing among
      patients who received long-term treatment for recurrent ovarian cancer. To
      document the frequency and contributing factors to the emergence of CKD, we
      initiated a retrospective review at two institutions. PATIENTS AND METHODS: Fifty
      six consecutive patients with recurrent ovarian cancer receiving treatment at New
      York University Cancer Institute were reviewed for the presence of renal disease
      in 1997-2010. At Shaare Zedek Medical Center, 73 consecutive patients with
      ovarian cancer were reviewed in 2002-2010. Patients were diagnosed with CKD if
      they had an estimated GFR <60 mL/minute per 1.73 m2 for >3 months and were staged
      according to the National Kidney Foundation guidelines. RESULTS: Thirteen
      patients (23%) developed stage >=3 CKD. Three patients had renal biopsies
      performed that showed thrombotic microangiopathy. CONCLUSIONS: CKD is emerging as
      a potential long-term consequence of current chemotherapy for recurrent ovarian
      cancer.

PMID- 22622147
TI  - A randomized, phase II trial of standard triweekly compared with dose-dense
      biweekly capecitabine plus oxaliplatin plus bevacizumab as first-line treatment
      for metastatic colorectal cancer: XELOX-A-DVS (dense versus standard).
AB  - BACKGROUND: Capecitabine administered for 7 days biweekly with oxaliplatin
      (XELOX) biweekly has been reported to have activity and safety profiles similar
      to those of standard capecitabine given for 14 days triweekly. Multiple studies
      have shown that the addition of bevacizumab to 5-fluorouracil-based chemotherapy
      is active and well tolerated. METHODS: Patients with metastatic colorectal cancer
      (mCRC) were randomized to XELOX plus bevacizumab using a standard triweekly cycle
      (Q3W) or a dose-dense biweekly cycle (Q2W) schedule. The primary endpoint was the
      progression-free survival (PFS) interval. This trial is registered on
      ClinicalTrials.gov (identifier, NCT00159432). RESULTS: In total, 435 U.S.
      patients were randomized. The median PFS intervals were 9.6 months in the Q3W
      group and 9.1 months in the Q2W group. The median overall survival times were
      28.4 months and 22.1 months and the median times to treatment failure were 5.5
      months and 3.4 months, respectively. Overall, gastrointestinal disorders were the
      most common (93%) adverse event (AE). Grade 3 or 4 AEs occurred in 75% and 81% of
      patients in the Q3W and Q2W groups, respectively. Treatment discontinuation as a
      result of diarrhea (5% versus 10%) and hand-foot syndrome (2% versus 9%) was less
      common in the Q3W group than in the Q2W group, respectively. CONCLUSIONS: Based
      on these results, the first-line treatment of U.S. patients with mCRC using a
      biweekly combination of XELOX and bevacizumab at the doses studied cannot be
      recommended. XELOX Q3W remains the preferred schedule for the management of mCRC.

PMID- 22622148
TI  - Squamous cell carcinoma of the oral cavity in nonsmoking women: a new and unusual
      complication of chemotherapy for recurrent ovarian cancer?
AB  - PURPOSE: To describe occurrences of oral squamous cell carcinoma (SCC) in
      patients who had received long-term pegylated liposomal doxorubicin (PLD) for
      ovarian cancer. PATIENTS AND METHODS: In our cohort of patients on maintenance
      PLD for ovarian and related mullerian epithelial malignancies, we encountered two
      patients with invasive SCC of the oral cavity (one of them multifocal) and one
      with high-grade squamous dysplasia. Review of patients at our institution
      receiving PLD for recurrent ovarian cancer identified three additional patients.
      The duration of treatment, cumulative PLD dose, human papillomavirus (HPV)
      positivity, BRCA status, stage at diagnosis, outcome, and other characteristics
      are reviewed. RESULTS: All five cases were nonsmokers with no known risk factors
      for HPV and four were negative for p16 expression. Four of the patients had known
      BRCA mutations whereas one tested negative. Cumulative doses of PLD were >1,600
      mg/m2 given over 30-132 months. Three had SCCs staged as T1N0 oral tongue,
      alveolar ridge (gingival), and multifocal oral mucosa; one had a T2N0 oral
      tongue; and one had dysplasia. After excision, two were given radiation but
      recurred shortly thereafter; the others remain well and have had no further
      exposure to cytotoxic drugs, including PLD. CONCLUSION: Awareness of this
      possible long-term complication during PLD treatment should enhance the
      likelihood of early detection of oral lesions in these patients. Decisions to
      continue maintenance PLD after complete response of the original cancer should
      perhaps consider the benefits of delaying ovarian cancer recurrence versus the
      possible risk for a secondary cancer.

PMID- 22622149
TI  - Multicenter retrospective study of 132 patients with unresectable small bowel
      adenocarcinoma treated with chemotherapy.
AB  - BACKGROUND: No standard chemotherapy regimen has been established for
      unresectable or recurrent small bowel adenocarcinoma (SBA). METHODS: Clinical
      courses of 132 patients with unresectable or recurrent SBA who received
      chemotherapy at 41 institutions in Japan were reviewed retrospectively. Patients
      were classified into five groups according to first-line chemotherapy regimens:
      fluoropyrimidine monotherapy (group A), fluoropyrimidine-cisplatin (group B),
      fluoropyrimidine-oxaliplatin (group C), fluoropyrimidine-irinotecan (group D),
      and other regimens (group E). RESULTS: The number of patients in each group was
      as follows: groups A, 60 patients; group B, 17 patients; group C, 22 patients;
      group D, 11 patients; and group E, 22 patients. Median progression-free survival
      (PFS) times were as follows: group A, 5.4 months; group B, 3.8 months; group C,
      8.2 months; group D, 5.6 months; and group E, 3.4 months. Median overall survival
      (OS) times were as follows: group A, 13.9 months; group B, 12.6 months; group C,
      22.2 months; group D, 9.4 months; and group D, 8.1 months. Patients in group C
      achieved significantly longer PFS times and substantially (but not significantly)
      longer OS times than patients in group A. After adjusting for clinical background
      characteristics, fluoropyrimidine-oxaliplatin therapy was a significant positive
      prognostic factor for PFS and OS times. CONCLUSION: The results suggest that
      fluoropyrimidine-oxaliplatin combination therapy is the most promising first-line
      chemotherapy regimen for unresectable or recurrent SBA.

PMID- 22622150
TI  - Squamous cell carcinoma of the oral tongue in two patients previously exposed to
      long-term pegylated liposomal doxorubicin.

PMID- 22622151
TI  - Diabetes mellitus is associated with increased mortality in patients receiving
      curative therapy for hepatocellular carcinoma.
AB  - BACKGROUND: Diabetes mellitus (DM) is closely associated with
      hepatocarcinogenesis. This study explores the prognostic impact of DM in patients
      who received curative therapy for localized hepatocellular carcinoma (HCC).
      METHODS: Patients who had been diagnosed with stage I or II HCC in 2003 and 2004
      and received surgical resection or local ablation therapy were identified from
      the population-based Taiwan National Cancer Registry. Data pertaining to DM and
      other comorbidities were retrieved from the Taiwan National Health Insurance
      database. Liver cancer-specific survival (LCS), liver disease-related survival
      (LDS) and overall survival (OS) rates were compared between patients with and
      without DM. The presence of other comorbidities and tumor status were adjusted
      using multivariate analysis. RESULTS: A total of 931 patients who fulfilled the
      study criteria were analyzed; 185 (20%) of them had DM (type 1 or type 2). The
      LCS, LDS, and OS rates were significantly worse for patients with DM than
      patients without DM (all p < .001). After adjusting for age, sex, tumor stage,
      treatment, and the presence of other comorbidities, DM remained an independent
      predictor of poorer LCS (hazard ratio [HR] = 1.57; p < .001), LDS (HR = 1.70; p <
      .001), and OS (HR = 1.69; p < .001). The associations between DM and mortality
      were consistent among subgroups, irrespective of tumor size, stage, treatment
      modality, and liver cirrhosis. CONCLUSIONS: DM is an independent factor for
      poorer prognosis in patients who received curative therapy for localized HCC.

PMID- 22622152
TI  - Isolation and characterization of two crude oil-degrading yeast strains, Yarrowia
      lipolytica PG-20 and PG-32, from the Persian Gulf.
AB  - Among six crude oil-degrading yeasts that were isolated from an oil-polluted area
      in the Persian Gulf, two yeast strains showed high degradation activity of
      aliphatic hydrocarbons. From an analysis of 18S rRNA sequences and biochemical
      characteristics, these strains were identified as Yarrowia lipolytica strains PG
      20 and PG-32. Gas Chromatography (GC) analysis of the crude oil remaining in the
      culture medium after 1 week at 30 degrees C showed that the strains PG-20 and PG
      32 degraded 68% and 58% of crude oil, respectively. The optimal growth condition
      and biodegradation of hydrocarbons was in ONR medium with an acidic pH (pH5).
      These two strains may degrade aliphatic hydrocarbons more efficiently than
      aromatic hydrocarbons, although strain PG-20 had better degradation than strain
      PG-32. The two Y. lipolytica strains reduce surface tension when cultured on
      hydrocarbon substrates (1% v/v). These strains showed a cell surface
      hydrophobicity higher than 70%. These results suggested that Y. lipolytica
      strains PG-20 and PG-32 have high crude oil degrading activity due to their high
      emulsifying activity and cell hydrophobicity. In conclusion, these yeast strains
      can be useful for the bioremediation process in the Persian Gulf and decreasing
      oil pollution in this marine ecosystem.

PMID- 22622153
TI  - Cytomegalovirus pneumonia in patients with inflammatory bowel disease: a
      systematic review.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) patients are at increased risk of
      cytomegalovirus (CMV) reactivation, and although CMV pneumonia may be a fatal
      disease in IBD patients, little information is available on this issue. The
      objectives of this study were to identify risk factors for the development of CMV
      pneumonia in IBD patients and to find useful information to better manage this
      potentially fatal complication. METHODS: A computerized search without language
      restrictions was conducted using PubMed and SCOPUS. An article was considered
      eligible for inclusion in the systematic review if it reported detailed data on
      patients with IBD presenting with pneumonia due to CMV. RESULTS: Overall, 12
      articles describing the history of 13 patients, published between the years 1996
      and 2011, were finally considered. All patients were adults with a mean age of 33
      years, and 11/13 were females. Fever and dyspnea were the most frequent symptoms.
      The most frequent radiological signs were bilateral pulmonary infiltrates. Six
      cases were complicated by hemophagocytic lymphohistiocytosis. Eight of the 13
      were transferred to intensive care units and four of them died. CONCLUSIONS: CMV
      pneumonia should always be suspected in IBD patients who present with fever and
      tachypnea, especially if the latter is worsening and/or is associated with
      dyspnea. Treatment must be early and specific.

PMID- 22622154
TI  - Localization of Nav 1.7 in the normal and injured rodent olfactory system
      indicates a critical role in olfaction, pheromone sensing and immune function.
AB  - Loss-of-function mutations in the pore-forming alpha subunit of the voltage-gated
      sodium channel 1.7 (Nav 1.7) cause congenital indifference to pain and anosmia.
      We used immunohistochemical techniques to study Nav 1.7 localization in the rat
      olfactory system in order to better understand its role in olfaction. We confirm
      that Nav 1.7 is expressed on olfactory sensory axons and report its presence on
      vomeronasal axons, indicating an important role for Nav 1.7 in transmission of
      pheromonal cues. Following neuroepithelial injury, Nav 1.7 was transiently
      expressed by cells of monocytic lineage. These findings support an emerging role
      for Nav 1.7 in immune function. This sodium channel may provide an important
      pharmacological target for treatment of inflammatory injury and inflammatory pain
      syndromes.

PMID- 22622155
TI  - Low-grade inflammation in young adults exposed to intrauterine hyperglycemia.
AB  - AIM: To investigate associations between fetal exposure to intrauterine
      hyperglycemia and plasma concentrations of interleukin-6 (IL-6) and high
      sensitivity C-reactive protein (hs-CRP) in adult offspring. METHOD: We studied
      597 offspring, aged 18-27 years, from four different groups concerning exposure
      to intrauterine hyperglycemia and genetic predisposition to type 2 diabetes
      (offspring of women with: gestational diabetes mellitus (GDM), risk factors for
      GDM but normal glucose tolerance, type 1 diabetes and women from the background
      population, respectively). The participants were characterized by fasting plasma
      levels of IL-6 and hs-CRP, a 75 g oral glucose tolerance test and anthropometric
      measurements. RESULTS: No association between intrauterine exposure to
      hyperglycemia and levels of IL-6 and hs-CRP in the offspring was found. In
      contrast maternal overweight (body mass index >= 25 kg/m(2)) was positively
      associated with levels of both IL-6 and hs-CRP (p for both=0.003). Offspring who
      had already developed overweight or conditions of abnormal glucose tolerance were
      characterized by higher levels of IL-6 and hs-CRP compared with the remaining
      offspring (all p<0.007). CONCLUSION: Maternal overweight but not exposure to
      intrauterine hyperglycemia was associated with low-grade inflammation in adult
      offspring.

PMID- 22622156
TI  - Heteropolytopic phosphanylarylthiolato ligands: formation of cis isomers of
      nickel(II), palladium(III) and platinum(III) complexes with 1-P(Biph)-2-SHC6H4
      (Biph = 1,1'-biphenyl-2,2'-diyl).
AB  - Reaction of the ditopic phosphanylarylthiol 1-P(Biph)-2-SHC(6)H(4) (BiphPSH, Biph
      = 1,1'-biphenyl-2,2'-diyl), prepared by lithiation-electrophilic substitution,
      with NiCl(2).6H(2)O, Na(2)[PdCl(4)] and [PtI(2)(cod)] (cod = 1,5-cyclooctadiene)
      in a 2:1 ratio and in the presence of NEt(3) led to formation of exclusively cis
      isomers of the square-planar complexes cis-[M{(1-P(Biph)-2-S-C(6)H(4))
      kappa(2)S,P}(2)] ([M{(BiphPS)-kappa(2)S,P}(2)]; M = Ni (1), Pd (2), Pt (3)).
      Density functional calculations support the assumption that this is probably due
      to intramolecular pi-pi interaction of the biphenyl groups, which results in
      enhanced stability of the cis isomers. Compound 1 is the first example of a
      structurally characterised mononuclear cis-bis(phosphanylthiolato)nickel(III)
      complex. Small amounts of the trinuclear complex [{PtI(1-P(Biph)-MU-2-S-C(6)H(4)
      kappa(2)S,P)}(3)] (4) are also formed besides the mononuclear platinum bis
      chelate complex 3.

PMID- 22622157
TI  - Obesity: etiologic and pathophysiological analysis.
AB  - Obesity has become a serious health problem worldwide because it is closely
      related to the leading causes of morbidity and mortality, including diabetes
      mellitus, hypertension, atherosclerosis, and dyslipidemia. It is therefore
      imperative for the scientific community to understand the main environmental and
      social-cultural factors, as well as organic disorders arising from breakdown of
      the physiological mechanisms that control energy balance in our body, all of
      which are ultimately responsible for development of obesity. Adequate
      understanding of the mechanisms involved in regulation of energy balance is
      therefore essential to understand the pathogenesis and pathophysiology of the
      growing pandemic of obesity. This study was intended to review the main factors
      involved in development of obesity and advances in understanding of the
      mechanisms that regulate body weight and appetite and their pathophysiology.

PMID- 22622158
TI  - Dietary treatment for X-linked adrenoleukodystrophy: is "Lorenzo's oil" useful?

PMID- 22622159
TI  - Partial hepatectomy improves the outcome of intraportal islet transplantation by
      promoting revascularization.
AB  - Revascularization of grafts is one of the important key factors for the success
      of islet transplantation. After partial hepatectomy, many growth factors such as
      hepatocyte growth factor and vascular endothelial growth factor are increased in
      the remnant liver. These growth factors have properties that promote
      angiogenesis. This might be an optimal environment for revascularization of
      islets transplanted intraportally. To verify this hypothesis, syngeneic islets
      (330 per recipient) were transplanted into the right hepatic lobes of
      streptozotocin-induced diabetic Balb/c mice with (hepatectomy group) or without
      (control group) left liver resection. Blood glucose was monitored for 28 d after
      transplantation. Glucose tolerance test was performed on post-operative day (POD)
      30, and histological assessments were performed on POD 7 and 30 respectively.
      Analysis revealed that 36.7% of the control and 90.0% of the hepatectomy mice
      attained normoglycemia during the observation period (*p = 0.0142). Glucose
      tolerance was improved in the hepatectomy group (Area under the curve of
      intraperitoneal glucose tolerance tests on POD 30, Control; 47,700 +/- 5,890
      min*mg/dl, Hepatectomy; 26,000 +/- 2,060 min*mg/dl: **p = 0.00314).
      Revascularization of grafted islets was more pronounced in the hepatectomy group
      (Vessel number per islet area on POD 7, Control; 3.20 +/- 0.463 * 10 (-4) /um (
      2) , Hepatectomy; 7.08 +/- 0.513 * 10 (-4) /um ( 2) : **p < 0.01). In the present
      study, partial hepatectomy (30%) improved the outcome of intraportal islet
      transplantation. Revascularization of islets transplanted into the liver may have
      been promoted by the induction of liver regeneration.

PMID- 22622161
TI  - Experimental set up for in situ transmission electron microscopy observations of
      chemical processes.
AB  - Recently, the applications of transmission electron microscopy (TEM) related
      techniques have extended from ex situ nanoscale characterization of structure and
      chemistry of products to dynamic measurements of nanostructures during reaction
      processes. Commercially available modified TEM specimen holders and TEM columns
      are being routinely employed to follow the structural and chemical changes at
      elevated temperatures and even under controlled atmosphere. Experiments performed
      under these rigorous conditions require careful considerations to avoid
      undesirable effects from the gas impurities or contaminations from TEM grids
      and/or holders. The reactivity of sample, grid, holder, TEM components, and
      gaseous environments must be evaluated for each reaction process. This tutorial
      is aimed to outline some of the important factors that should be considered for
      experimental set up used for in situ observations to ensure the results are
      comparable to the ones obtained during ex situ experiments under identical
      conditions.

PMID- 22622160
TI  - A role for Atg8-PE deconjugation in autophagosome biogenesis.
AB  - Formation of the autophagosome is likely the most complex step of macroautophagy,
      and indeed it is the morphological and functional hallmark of this process;
      accordingly, it is critical to understand the corresponding molecular mechanism.
      Atg8 is the only known autophagy-related (Atg) protein required for autophagosome
      formation that remains associated with the completed sequestering vesicle.
      Approximately one-fourth of all of the characterized Atg proteins that
      participate in autophagosome biogenesis affect Atg8, regulating its conjugation
      to phosphatidylethanolamine (PE), localization to the phagophore assembly site
      and/or subsequent deconjugation. An unanswered question in the field regards the
      physiological role of the deconjugation of Atg8-PE. Using an Atg8 mutant that
      bypasses the initial Atg4-dependent processing, we demonstrate that Atg8
      deconjugation is an important step required to facilitate multiple events during
      macroautophagy. The inability to deconjugate Atg8-PE results in the
      mislocalization of this protein to the vacuolar membrane. We also show that the
      deconjugation of Atg8-PE is required for efficient autophagosome biogenesis, the
      assembly of Atg9-containing tubulovesicular clusters into
      phagophores/autophagosomes, and for the disassembly of PAS-associated Atg
      components.

PMID- 22622162
TI  - Dermatomyositis presenting with focal scleroderma-like skin changes.
AB  - OBJECTIVE: To describe an unusual focal scleroderma-like skin changes in patient
      with dermatomyositis. METHODS: Review of clinical records, laboratory
      investigations, and muscle and skin biopsies. RESULTS: The patient developed
      unusual skin lesions characterized by symmetrical atrophy and hardening of focal
      skin and muscle over the lateral upper arms and posterior shoulders, and the left
      temporal and pectoral areas. Extensive blood work-up for scleroderma and other
      connective-tissue diseases was negative. A skin biopsy showed distinct pathologic
      features including increased interstitial mucin, hyperpigmentation, and
      perivascular lymphocytic inflammation without severe fibrosis. The scleroderma
      like skin changes and muscle weakness improved with immunotherapy. CONCLUSIONS:
      Dermatomyositis can manifest with focal scleroderma-like skin changes clinically
      and reticular erythematous mucinosis-like changes pathologically, and these
      distinct skin changes represent a new variant of skin lesions of dermatomyositis.

PMID- 22622163
TI  - Interobserver agreement in case history evaluation in carpal tunnel syndrome.
AB  - OBJECTIVES: The case history is the cornerstone for the diagnosis of carpal
      tunnel syndrome (CTS). The value of neurological examination in CTS seems
      limited. In this study, we investigated the interobserver agreement in case
      history of CTS and the potential additional value of neurological examination.
      METHODS: Case history was taken and neurological examination was done in all
      patients referred for a possible CTS during a 6-month period. This was done
      independently by 2 senior neurologists. RESULTS: We studied 119 patients. The
      interobserver agreement for the conclusion of CTS after history was high (k =
      0.79). Neurological examination rarely changed the diagnosis based on the case
      history. CONCLUSIONS: This study shows a high interobserver agreement in the
      diagnosis of CTS based on patient history alone. Neurological examination rarely
      changed this diagnosis, suggesting a prominent role for the case history and a
      limited role for neurological examination. This may have practical implications.

PMID- 22622164
TI  - The quantitative myasthenia gravis score:  comparison with clinical,
      electrophysiological, and laboratory markers.
AB  - OBJECTIVE: To determine whether the quantitative myasthenia gravis score (QMGS)
      accurately represents disease severity in patients with myasthenia gravis (MG).
      METHODS: One hundred thirty-five patients with MG from 2 previous randomized
      studies were included. QMGS correlation with the Myasthenia Gravis Foundation of
      America (MGFA) score, quality of life scale, acetylcholine receptor antibodies
      (AChRAbs), and electrophysiological parameters was studied. RESULTS: The QMGS
      showed a good correlation with the MGFA scale (r2 = 0.54, P < 0.0001), jitter (rs
      = 0.40, P < 0.0001), and 15-item quality of life scale (rs = 0.41, P = 0.007) and
      was less well correlated with the 60-item myasthenia gravis-specific quality of
      life survey and other electrophysiological markers. No correlation was
      demonstrated with AchRAb titers, but AchRAb-positive patients had higher QMGS
      (14.2 +/- 4.5) than AchRAb-negative patients (12.0 +/- 3.7, P = 0.008).
      CONCLUSIONS: These results demonstrate that the QMGS is a valid marker for
      disease severity as shown by the MGFA scale, quality of life scale, and jitter,
      supporting the use of the QMGS as a primary outcome measure in clinical trials of
      MG.

PMID- 22622165
TI  - A novel MPZ gene mutation in exon 2 causing late-onset demyelinating Charcot
      Marie-Tooth disease.
AB  - The myelin protein zero gene (MPZ) encodes the major structural protein component
      of myelin in the peripheral nervous system. More than 120 mutations in MPZ have
      been detected so far. Clinical phenotypes include CMT1B, CMT2, Dejerine-Sottas
      syndrome, and congenital hypomyelination neuropathy. We report a new previously
      unreported mutation in the MPZ gene causing a demyelinating peripheral
      neuropathy. The initial apparent absence of a family history resulted in the
      patient being treated for an inflammatory neuropathy with some subjective
      improvement. We subsequently identified another affected member of the same
      family with the same genotype leading to the correct diagnosis. Both the affected
      individuals had an 8-base pair deletion, c.160_167delTCCCGGGT in MPZ exon 2.

PMID- 22622166
TI  - Late-onset axial myopathy and camptocormia in a calpainopathy carrier.
AB  - Camptocormia is a debilitating gait disorder characterized by the hyperflexion of
      the thoracolumbar spine during the upright position. Its etiologies are
      heterogenous, including parkinsonism and various neuromuscular disorders. Here,
      we report a camptocormia patient due to a late-onset axial myopathy with numerous
      lobulated fibers. The patient's father reportedly had similar symptoms. Myriad
      lobulated fibers are common among patients with an autosomal recessive muscular
      dystrophy due to calpain-3 gene (CAPN3) mutations or calpainopathy. CAPN3
      sequencing revealed a single c.759-761delGAA mutation. Calpainopathy carriers are
      generally asymptomatic. The presence of lobulated fibers in this patient suggests
      that camptocormia could be a manifestation of calpainopathy carrier, although the
      possibility of a coexisting undiagnosed myopathy cannot be excluded. The current
      patient should spur the evaluation of camptocormia among calpainopathy carriers.

PMID- 22622167
TI  - Morvan syndrome:  a case report and review of the literature.
AB  - Morvan syndrome is characterized by central, autonomic, and peripheral
      hyperactivity. Examples of central hyperactivity include confusion, memory
      problems, hallucinations, insomnia, and myoclonus; examples of autonomic
      hyperactivity include hyperhidrosis and fluctuations in blood pressure; examples
      of peripheral hyperreactivity include clinical or electrophysiological evidence
      of painful cramps, myokymia, and neuromyotonia. We present a typical case of
      Morvan syndrome and the first detailed review of the clinical and therapeutic
      literature of all 27 cases from the English language literature. Morvan syndrome
      is considered to be an autoimmune disorder and antibodies against voltage-gated
      potassium channels are found in most cases. Oral immunomodulatory therapy,
      intravenous immunoglobulin, and plasmapharesis may be entertained. Thymoma is
      found in approximately 50% of cases and thymectomy may be curative as in our
      particular case.

PMID- 22622168
TI  - Paraneoplastic Isaacs' syndrome: a case series and review of the literature.
AB  - OBJECTIVE: Isaacs' syndrome is a rare disease resulting from hyperexcitability of
      peripheral nerves causing continuous muscle fiber activity characterized by
      muscle twitching and stiffness at rest and delayed muscle relaxation after
      voluntary contraction. Our objective was to discuss the relationship of Isaacs'
      syndrome to paraneoplastic syndromes as reported in the available literature and
      in 3 patients evaluated at our academic medical center. METHODS: We review the
      literature on Isaacs' syndrome and describe 3 patients in whom Isaacs' syndrome
      heralded underlying malignancy or benign neoplasm, including their presenting
      symptoms, electrophysiologic findings, and laboratory and pathology results.
      RESULTS: In all 3 cases, clinical and electrodiagnostic testing was suggestive of
      Isaacs' syndrome. Two patients tested positive, and one was negative for voltage
      gated potassium channel antibodies. Two of the patients developed malignant
      tumors, that is, one was diagnosed with metastatic thymoma and one with
      lymphoplasmacytic lymphoma, ranging from 6 months to 1 year after the diagnosis
      of Isaacs' syndrome. One patient was diagnosed with a spinal cord
      hemangioblastoma 5 years after he was diagnosed with Isaacs' syndrome.
      CONCLUSIONS: Our case series highlights the association of Isaacs' syndrome with
      a variety of neoplasms both malignant and benign. Our report also underscores the
      fact that Isaacs' syndrome may be diagnosed several years before a neoplasm is
      discovered. In our cases, Isaacs' syndrome overlapped with other neuromuscular
      disorders, that is, myasthenia gravis in a patient with thymoma and chronic
      inflammatory demyelinating polyneuropathy in a patient with lymphoplasmacytic
      lymphoma with paraproteinemia. To our knowledge, this is the first report of an
      association between Isaacs' syndrome with lymphoplasmacytic lymphoma and a spinal
      cord hemangioblastoma.

PMID- 22622169
TI  - A case of monomelic amyotrophy of the upper limb:  MRI findings and the
      implication on its pathogenesis.
AB  - Monomelic amyotrophy of the upper limb or Hirayama disease is mostly considered
      as an anterior horn disorder resulting from local ischemia, triggered by arterial
      compression from an anterior shifting of the posterior cervical dura upon neck
      flexion. However, such a dural shifting is not universally seen. We report on a
      Caucasian male patient who developed a slowly progressive unilateral distal hand
      weakness in his teens. His clinical and electromyographic findings were
      consistent with Hirayama disease. Local anterior cervical cord atrophy was
      observed without dural shifting on the dynamic magnetic resonance imaging. Axial
      magnetic resonance imaging demonstrated signal changes of "snake-eye" appearance
      in the cervical anterior horn region, similar to ischemic myelopathies caused by
      various etiologies. This case illustrated that even without dural shifting, a
      mechanism of anterior spinal cord ischemia could still be responsible for the
      pathogenesis of Hirayama disease.

PMID- 22622170
TI  - Buttock-crush syndrome.

PMID- 22622171
TI  - Brachial plexus atrophy in chronic inflammatory demyelinating
      polyradiculoneuropathy.

PMID- 22622173
TI  - Generalized skin reactions in patients with MDS and CMML treated with
      azacitidine: Effective management with concomitant prednisolone.

PMID- 22622174
TI  - Ventral hippocampal molecular pathways and impaired neurogenesis associated with
      5-HT1A and 5-HT1B receptors disruption in mice.
AB  - The serotonergic system has been widely implicated in stress related psychiatric
      disorders such as depression and anxiety. Generation of receptor knockout mice
      has offered a new approach to study processes underlying anxiety. For instance,
      knockout mice for both 5-HT(1A) and 5-HT(1B) receptors (5-HT(1A/1B)(-/-)) display
      an anxious phenotype, associated with robust physiological and neurochemical
      changes related to brain serotonin function. As ventral hippocampus is a key
      region in the mediation and genesis of anxiety, we explored the transcriptome
      changes induced by the genetic inactivation of these two receptors in 5
      HT(1A/1B)(-/-) mice. Dissociation of ventral vs. dorsal hippocampus was confirmed
      by the over-expression of selective markers in both regions. 723 genes were
      observed up/down regulated in 5-HT(1A/1B)(-/-) mice. Using Ingenuity, biological
      networks and signal transduction pathway analysis corresponding to the identified
      gene revealed putative dysregulation of nervous system development and function,
      especially genes associated with long-term potentiation and adult neurogenesis
      (including Bdnf, Camk2a, Camk4, and Klf9). Furthermore, immunohistochemistry
      experiments studying adult hippocampal neurogenesis in adult 5-HT(1A/1B)(-/-)
      mice showed a decreased survival, but not proliferation of newborn cells in our
      model.

PMID- 22622175
TI  - Striatal MU-opioid receptor availability predicts cold pressor pain threshold in
      healthy human subjects.
AB  - Previous PET studies in healthy humans have shown that brain MU-opioid receptor
      activation during experimental pain is associated with reductions in the sensory
      and affective ratings of the individual pain experience. The aim of this study
      was to find out whether brain MU-opioid receptor binding at the resting state, in
      absence of painful stimulation, can be a long-term predictor of experimental pain
      sensitivity. We measured MU-opioid receptor binding potential (BP(ND)) with MU
      opioid receptor selective radiotracer [(11)C]carfentanil and positron emission
      tomography (PET) in 12 healthy male subjects. Later, we recruited these subjects
      to participate in a separate psychophysical testing session to measure cold
      pressor pain threshold, cold pressor pain tolerance and tactile sensitivity with
      von Frey monofilaments. We used both voxel-by-voxel and region-of-interest image
      analyses to examine the potential associations between MU-opioid receptor BP(ND)
      and psychophysical measures. The results show that striatal MU-opioid receptor
      BP(ND) predicts cold pressor pain threshold, but not cold pressor pain tolerance
      or tactile sensitivity. This finding suggests that striatal MU-opioid receptor
      density is involved in setting individual pain threshold.

PMID- 22622176
TI  - The emerging concept of chronic kidney disease without clinical proteinuria in
      diabetic patients.
AB  - The natural history of diabetic nephropathy was defined in the 1980s on the basis
      of longitudinal studies undertaken in patients with type 1 and type 2 diabetes.
      However, an increasing number of studies have indicated that certain diabetic
      patients do not present with the same evolution as was then defined: for example,
      some often have significant initial deterioration of glomerular filtration rate
      whereas, in others, microalbuminuria is reduced spontaneously. Chronic kidney
      disease (CKD) may be accompanied, rather than preceded, by macroalbuminuria, or
      it may develop in patients with microalbuminuria or even in those with
      albuminuria levels that revert to normal. CKD can also develop in patients whose
      albuminuria levels remain normal. Progression to macroalbuminuria is, in fact,
      less frequent than regression to normoalbuminuria or no change in
      microalbuminuria status in diabetic patients with microalbuminuria, especially in
      type 1 diabetes. Some experience progressive deterioration of renal function due
      to diabetes without developing significant proteinuria: this is seen fairly
      frequently and can affect 50% of patients with renal insufficiency. Such cases
      are more often older patients treated with renin-angiotensin system blockers who
      usually have a history of cardiovascular disease. Evolution to end-stage renal
      disease is slower in this subgroup of patients, although histological analyses
      may show surprisingly advanced glomerular lesions. The main parameters of
      surveillance remain regular monitoring of glycaemia, and control of blood
      pressure and the evolution of initial albuminuria levels. Nevertheless, why some
      patients exhibit conventional diabetic nephropathy while others have slower
      declines in renal function associated with normal albuminuria levels or
      microalbuminuria is unclear. It is hoped that the new pathological classification
      of diabetic nephropathy will help in our understanding of these discrepancies.

PMID- 22622177
TI  - The deubiquitinating enzyme USP36 controls selective autophagy activation by
      ubiquitinated proteins.
AB  - Initially described as a nonspecific degradation process induced upon starvation,
      autophagy is now known also to be involved in the degradation of specific
      ubiquitinated substrates such as mitochondria, bacteria and aggregated proteins,
      ensuring crucial functions in cell physiology and immunity. We report here that
      the deubiquitinating enzyme USP36 controls selective autophagy activation in
      Drosophila and in human cells. We show that dUsp36 loss of function autonomously
      inhibits cell growth while activating autophagy. Despite the phenotypic
      similarity, dUSP36 is not part of the TOR signaling pathway. Autophagy induced by
      dUsp36 loss of function depends on p62/SQSTM1, an adaptor for delivering cargo
      marked by polyubiquitin to autophagosomes. Consistent with p62 requirement,
      dUsp36 mutant cells display nuclear aggregates of ubiquitinated proteins,
      including Histone H2B, and cytoplasmic ubiquitinated proteins; the latter are
      eliminated by autophagy. Importantly, USP36 function in p62-dependent selective
      autophagy is conserved in human cells. Our work identifies a novel, crucial role
      for a deubiquitinating enzyme in selective autophagy.

PMID- 22622178
TI  - [Prevention of diabetes mellitus type 2].
AB  - Diabetes mellitus type 2 (DM2) is one of the most important risk factors for
      cardiovascular disease. The increasing prevalence worldwide is generating a great
      health and social concern. Clinical intervention studies such as the UKPDS have
      shown that although the metabolic control of DM2 may improve with intensive
      intervention programs, these are highly expensive and do not lead to an optimal
      metabolic control. For this reason, one of the main challenges in DM2 at present
      is its prevention. The natural history of DM2 is sufficiently well known and we
      know that before it is diagnosed, there is a former, often lasting years, "pre
      diabetic state" that behaves as a vascular risk factor. In recent years numerous
      studies have shown that prevention of DM2 is possible. We critically review here
      the current situation of the disease.

PMID- 22622179
TI  - Cancer in parents of persons with schizophrenia: is there a genetic protection?
AB  - A reduced risk for cancer has been noted among persons with schizophrenia as well
      as their first degree relatives. One explanation for these findings suggests that
      genes associated with schizophrenia confer reduced cancer susceptibility. Given
      the well documented genetic factor in schizophrenia it could thus be expected
      that cancer incidence rates should be lower in persons with schizophrenia with a
      known family history of schizophrenia compared to persons with sporadic
      schizophrenia, as well as their first degree relatives. This study investigated
      the risk for cancer among the biological parents of persons with schizophrenia
      accounting for the familial aggregation. Linkage was conducted between national
      population, psychiatric and cancer databases. Standardized incidence rates for
      all cancer sites were calculated by comparing the parents' rates with those of
      the general population. In addition, the association between familial aggregation
      of schizophrenia and risk for cancer was calculated among the parents. A reduced
      cancer risk was found among the parents compared to the general population (SIR
      0.8, 95% CI 0.8-0.9). However, no evidence of decreased risk was associated with
      familial schizophrenia. Thus, no association between familial aggregation and
      cancer incidents was found with regard to most cancer sites. Moreover, a small,
      but not statistically significant increased risk of colon cancer was associated
      with familial aggregation scores among the parents (OR 1.2, 95% CI 1.0-1.5).
      These findings undermine the support to the genetic explanation for the reduced
      risk for cancer in schizophrenia among patients and their biological parents.

PMID- 22622189
TI  - The conversion of multinuclear MU-oxo titanium(IV) species in the reaction of
      Ti(O(i)Bu)4 with branched organic acids; results of structural and spectroscopic
      studies.
AB  - Crystalline materials have been synthesized in reactions of titanium(iv)
      tetraisobutoxide with branched organic acids (HOOCR', R' = CMe(2)Et, (t)Bu,
      CH(2)(t)Bu) in the molar ratio 1:1 at room temperature under Ar atmosphere.
      Particular attention has been paid to the structural and spectral
      characterization of metastable intermediate complexes of general formula
      [Ti(7)O(9)(O(i)Bu)(4)(HO(i)Bu)(OOCCMe(2)Et)(6)](2) (1) and
      [Ti(6)O(5)(O(i)Bu)(6)(OOC(t)Bu)(8)] (3), and their conversion towards more
      structurally stable compounds [Ti(6)O(6)(O(i)Bu)(6)(OOCC(Me)(2)Et)(6)] (2) and
      [Ti(6)O(6)(H(2)O)(2)(O(i)Bu)(6)(OOC(t)Bu)(6)] (4). The hexanuclear structure of
      (5) ([Ti(6)O(6)(O(i)Bu)(6)(OOCCH(2)(t)Bu)(6)]) has been postulated on the basis
      of IR and (13)C NMR spectroscopic data analysis. The possible reaction pathways
      which may occur during the formation of the above mentioned compounds are also
      discussed.

PMID- 22622190
TI  - A selective Seoul-Fluor-based bioprobe, SfBP, for vaccinia H1-related phosphatase
      -a dual-specific protein tyrosine phosphatase.
AB  - We report a Seoul-Fluor-based bioprobe, SfBP, for selective monitoring of protein
      tyrosine phosphatases (PTPs). A rational design based on the structures at the
      active site of dual-specific PTPs can enable SfBP to selectively monitor the
      activity of these PTPs with a 93-fold change in brightness. Moreover, screening
      results of SfBP against 30 classical PTPs and 35 dual-specific PTPs show that it
      is selective toward vaccinia H1-related (VHR) phosphatase, a dual-specific PTP
      (DUSP-3).

PMID- 22622191
TI  - [Pregnancy and extra-gastrointestinal stromal tumor: an exceptional association].
AB  - Extra-gastrointestinal stromal tumors (EGIST) are rare entities. The coexistence
      of a gastrointestinal stromal tumor and pregnancy is exceptional. We describe a
      case of this association, three years after the first diagnosis of EGIST made
      during exploratory laparotomy for abdominal-pelvic mass. We report the diagnostic
      difficulties and management of pregnancy on recurrence of EGIST tumor.

PMID- 22622192
TI  - [Pregnancy in women aged 43 years or older: maternal and perinatal risks].
AB  - OBJECTIVES: The proportion of women with advanced age at the time of delivery
      increases constantly, partly due to assisted reproductive technologies. Maternal
      morbidity is known to increase with maternal age, whereas data on perinatal
      outcomes are controversial. Risks of maternal and perinatal complications may be
      elevated among older pregnant women. The purpose of this study is to quantify
      these risks among 43 years or older women in comparison with women aged 25 to 35
      years, the age known to be optimal for a pregnancy. PATIENTS AND METHODS: A
      retrospective study was conducted during three years (2008-2010) in a level 3
      maternity unit, comparing maternal and perinatal outcomes between women who were
      at least 43 years old and a control group composed of drawn lots mothers between
      25 and 35 years of age at the time of delivery. Maternal and perinatal outcomes
      were studied using uni- and multivariate analysis. As in vitro fertilization
      (IVF) and twin pregnancy are associated with maternal age and several
      complications, we compared 43 years or older women with a control group using
      three categories: "43 years or older without IVF", "43 years or older with IVF
      and singleton" and "43 years or older with IVF and twin". RESULTS: Three hundred
      and sixty one women aged at least 43 years at the time of delivery (mean age:
      44.6 years) were compared with 361 women aged 25 to 35 years (mean age: 31.0
      years). Cesarean and preterm delivery rates were significantly higher in the
      study group (43.5% vs. 21.7% and 18.4% vs. 6.5% respectively, p<0.05), with
      higher risks after adjustment (adjusted OR=2.3 [1.6-3.4] and 2.4 [1.3-4.3],
      respectively). Gestational hypertension and preeclampsia rates were significantly
      higher among the 43 years or older women compared with the control group (11.1%
      vs 3.6% and 8.3% vs. 3.1% respectively, P<0.05) but this difference was not
      significant in multivariate analysis. The rate of preterm delivery was four fold
      higher among the 43 years or older women with IVF and twin in comparison with
      those who have a spontaneous pregnancy (52.3% vs. 13.0%, P<0.001). Cesarean
      delivery rate was also significantly increased in this subgroup. CONCLUSION: Most
      women having a spontaneous singleton pregnancy at 43 years or older have an
      uneventful pregnancy outcome. However, in comparison with the women aged 25 to 35
      years, they have significantly higher risks of cesarean and preterm delivery.
      These risks significantly increase with IVF and twin pregnancy among older women.
      Women aged 43 years or older should be informed about these risks to make an
      enlightened decision, particularly when IVF is needed.

PMID- 22622193
TI  - [Chorionic villus sampling training method].
AB  - OBJECTIVES: Chorionic villus sampling (CVS) in the first trimester of pregnancy
      has become a major tool in prenatal diagnosis. To increase the safety of CVS
      during training period, we have built a "BT-Trainer". MATERIALS AND METHODS: A
      medical device has been developed which simulates the in vivo procedure with the
      various layers to cross. The stratum of the layer and the accessibility of the
      placenta can modulate the level difficulty. CONCLUSION: Traditional strategies
      for clinical teaching are often insufficient and trainees may fail to achieve
      competence in even basic procedural skills. We present herein an easy and
      reproducible model of "BT-Trainer" which allows a safe and repeatable training.
      Efficacy of this model is currently under evaluation in a teaching program. This
      trainer could help gynaecologists in order to learn gradually and safely the
      technique and to enhance their skills and coordination.

PMID- 22622194
TI  - [Predictors of postpartum post-traumatic stress disorder in primiparous mothers].
AB  - OBJECTIVES: Identify the potential predictors of postpartum post-traumatic stress
      disorder (PTSD) in primiparous mothers. MATERIALS AND METHODS: This longitudinal
      prospective study evaluated the prevalence of obstetric complications and
      psychiatric disorders (anxiety, depression, psychic dissociation, PTSD,
      personality) in the immediate postpartum and after 3-6 months. RESULTS: Among 456
      hospitalized primiparous mothers, 314 were recruited and 212 followed-up
      prospectively. The prevalence of PTSD symptoms was high and stable through the
      postpartum (12.7% versus 13.6%). Significant risk factors were associated with
      postpartum PTSD: social isolation, celibacy or divorce (OR=6.6; P<0.02), history
      of abortion (OR=6.2; P<0.01) or of infertility (OR=10.4; P<0.007), too long
      subjective length of labour (OR=3.5; P<0.03), mothers' perceptions of obstetric
      complications (OR=18.5; P<0.003), high anxiety level at the maternity hospital
      (OR=3.9; P<0.03), PTSD symptoms after childbirth (OR=6.7; P<0.01) and dependent
      personality disorder (OR=23.2; P<0.001). CONCLUSION: Subjective experience of
      childbirth, history of obstetric complications, social isolation and dependent
      personality disorder and high level of stress-anxiety after childbirth are
      significant predictive factors of postpartum PTSD (3-6 months). The early
      identification of these factors should lead to early therapeutic intervention in
      the mothers at risk of PTSD.

PMID- 22622195
TI  - Predator and non-predator long-distance calls in Guereza colobus monkeys.
AB  - East African Guereza colobus monkey males are known for their conspicuous roaring
      behaviour; a spectacle that can dominate the predawn hours of African forests.
      Recent research has shown that these monkeys also produce roars during daytime
      hours in response to predators. While roars to leopards and eagles differ in how
      roaring phrases are assembled into sequences, there are no obvious structural
      differences between predawn roars and roars to eagles. Although recipients could
      use daytime information to disambiguate between the two contexts, this may be a
      risky strategy because eagles can be active before dawn. We carried out acoustic
      analyses, which showed that the duration of the first roaring phrase was
      significantly longer in predawn roars compared to eagle roars. Furthermore, the
      initial call repetition rate was faster in response to eagle roars compared to
      predawn roars. Apart from these two differences, all other acoustic
      characteristics were identical between the two contexts. Although these monkeys
      exhibit some of the most basic vocal behaviour found in non-human primates,
      callers are able to provide reliable contextual information by varying the
      duration and assemblage of individual vocal units. Playback experiments are
      needed to confirm whether recipients relate these acoustic differences to
      different contexts.

PMID- 22622196
TI  - Cell-free protein synthesis from a single copy of DNA in a glass microchamber.
AB  - To achieve a cell-mimetic reaction environment, we fabricated and tested quartz
      microchambers for conducting protein synthesis using an in vitro transcription
      and translation system, the PURE system. By introducing a glass microchamber and
      blocking the surface of the chamber with amino acids, the concentration of the
      synthesized marker protein (green fluorescent protein, GFP) was significantly
      improved compared to that in the poly(dimethylsiloxane) (PDMS) microchamber. The
      concentration was below the detection limit in the PDMS microchambers, whereas
      the glass microchambers yielded 700 nM GFP, representing 41% of the bulk
      reaction. There was no detectable difference when the GFP synthesis was performed
      in microchambers with sizes ranging from 40 fL to 7 pL, indicating that the
      present microchamber system can serve as a cell-sized test tube with a variable
      reaction volume. Finally, we demonstrated that two different proteins, GFP and
      beta-galactosidase, can be expressed from single genes in our experimental setup.
      Quantized and distinctive signals from proteins synthesized from 0, 1, or 2
      copies of genes were obtained. The microchamber presented here can be utilized
      not only to study the effects of compartment volume on protein synthesis but also
      for the comprehensive analysis of complex biochemical reactions in cell-mimetic
      environments.

PMID- 22622198
TI  - High-throughput antibody sequencing reveals genetic evidence of global regulation
      of the naive and memory repertoires that extends across individuals.
AB  - Vast diversity in the antibody repertoire is a key component of the adaptive
      immune response. This diversity is generated centrally through the assembly of
      variable, diversity and joining gene segments, and peripherally by somatic
      hypermutation and class-switch recombination. The peripheral diversification
      process is thought to only occur in response to antigenic stimulus, producing
      antigen-selected memory B cells. Surprisingly, analyses of the variable,
      diversity and joining gene segments have revealed that the naive and memory
      subsets are composed of similar proportions of these elements. Lacking, however,
      is a more detailed study, analyzing the repertoires of naive and memory subsets
      at the level of the complete V(D)J recombinant. This report presents a thorough
      examination of V(D)J recombinants in the human peripheral blood repertoire,
      revealing surprisingly large repertoire differences between circulating B-cell
      subsets and providing genetic evidence for global control of repertoire diversity
      in naive and memory circulating B-cell subsets.

PMID- 22622197
TI  - Lineage-specific adjacent IFNG and IL26 genes share a common distal enhancer
      element.
AB  - Certain groups of physically linked genes remain linked over long periods of
      evolutionary time. The general view is that such evolutionary conservation
      confers 'fitness' to the species. Why gene order confers 'fitness' to the species
      is incompletely understood. For example, linkage of IL26 and IFNG is preserved
      over evolutionary time yet Th17 lineages express IL26 and Th1 lineages express
      IFNG. We considered the hypothesis that distal enhancer elements may be shared
      between adjacent genes, which would require linkage be maintained in evolution.
      We test this hypothesis using a bacterial artificial chromosome transgenic model
      with deletions of specific conserved non-coding sequences. We identify one
      enhancer element uniquely required for IL26 expression but not for IFNG
      expression. We identify a second enhancer element positioned between IL26 and
      IFNG required for both IL26 and IFNG expression. One function of this enhancer is
      to facilitate recruitment of RNA polymerase II to promoters of both genes. Thus,
      sharing of distal enhancers between adjacent genes may contribute to evolutionary
      preservation of gene order.

PMID- 22622200
TI  - A concise route to indoloazocines via a sequential Ugi-gold-catalyzed
      intramolecular hydroarylation.
AB  - A diversity oriented approach for the synthesis of indoloazocines is reported
      employing an Ugi reaction followed by a gold-catalyzed intramolecular
      hydroarylation.

PMID- 22622199
TI  - Bisphosphonate use and the risk of breast cancer: a meta-analysis of published
      literature.
AB  - Bisphosphonates are widely used in clinical practice to prevent and treat
      osteoporosis and cancer-induced bone loss. Recently, analysis of results of
      several published observational studies found that women who used bisphosphonates
      had a significant reduction in the risk of breast cancer compared with nonusers.
      However, the findings were inconsistent. We systematically searched MEDLINE and
      EMBASE databases through June 1, 2011. The eligibility determination and the data
      extraction were conducted independently by 2 of the authors. A random-effect
      model was used to obtain the pooled estimates of effect. We identified 2 cohort
      studies and 2 case-control studies that were eligible for analysis, which
      involved 15,363 patients with breast cancer and 84,931 bisphosphonate users. The
      results of our meta-analysis revealed that women who received bisphosphonates
      have a 15% risk reduction of any breast cancer (pooled risk ratio [RR], 0.85 [95%
      confidence interval {CI}, 0.74-0.98]; P = .03) and a 32% risk reduction of
      invasive breast cancer (pooled RR, 0.68 [95% CI, 0.59-0.80]; P < .001) compared
      with nonusers. In addition, there was a significant dose-response relationship
      between the duration of bisphosphonate use and breast cancer risk. A
      significantly protective effect of bisphosphonates was observed in patients who
      used bisphosphonates for more than 1 year before the diagnosis of breast cancer
      compared with nonusers. The bisphosphonate users had a risk reduction of breast
      cancer by 8% (pooled RR, 0.92 [95% CI, 0.87-0.96]; P = .001) for each additional
      year of the duration of bisphosphonate use. The use of bisphosphonates may have a
      beneficial effect on breast cancer risk.

PMID- 22622201
TI  - Regeneration and bioengineering of the gastrointestinal tract: current status and
      future perspectives.
AB  - The present review aims to illustrate the strategies that are being implemented
      in regenerative medicine to treat diseases that affect the digestive tract.
      Possible avenues are twofold: organ bioengineering, where cells are seeded on
      biological or synthetic scaffolding materials ex vivo and allowed to either
      mature in bioreactors or be implanted without undergoing any maturation; and
      regeneration per se, where the diseased tissue or organ is regenerated by
      recapitulation of its multi-step ontogenesis. This latter avenue may be induced
      either in vivo or ex vivo. While bioengineering technology has already
      manufactured segments of the digestive tract and sphincters, pure regeneration of
      any segment of the digestive tract has not yet been described. However, models of
      regeneration extrapolated from simple organisms are elucidating the complex yet
      fascinating mechanisms that regulate the ontogenesis of the digestive tract and
      are paving the way for the development of new regenerative technologies and
      methods.

PMID- 22622202
TI  - Changes of faecal microbiota in patients with Crohn's disease treated with an
      elemental diet and total parenteral nutrition.
AB  - BACKGROUND: Intestinal microbiota contributes to the pathogenesis of Crohn's
      disease. Elemental diet and total parenteral nutrition are effective therapies
      for Crohn's disease; however, changes of microbiota as a result of both
      treatments have not been fully elucidated. AIM: To elucidate changes of faecal
      microbiota in Crohn's disease patients treated with elemental diet and total
      parenteral nutrition. METHODS: Stool samples were collected from 33 active
      Crohn's disease patients and 17 healthy subjects, and recollected after elemental
      diet (8 patients) and total parenteral nutrition (9 patients). Terminal
      restriction fragment length polymorphism analysis of bacterial 16srDNA was
      performed to evaluate the whole microbiota. Specific quantitative PCR was then
      used to determine populations of predominant bacterial groups. RESULTS: In
      Crohn's disease patients, the number of terminal restriction fragments, which
      reflects bacterial species, was significantly lower. Populations of total
      bacteria and Bifidobacterium were significantly lower and the ratio of
      Enterococcus was higher. The number of terminal restriction fragments was
      significantly decreased after total parenteral nutrition, but not after elemental
      diet. Population of Bacteroides fragilis significantly decreased after elemental
      diet, while population of Enterococcus significantly increased after total
      parenteral nutrition. CONCLUSION: Faecal microbiota in Crohn's disease patients
      was markedly different from healthy subjects. Species diversity was reduced by
      total parenteral nutrition, but not by elemental diet.

PMID- 22622203
TI  - Transoral incisionless fundoplication with EsophyX(r) for treatment of gastro
      oesphageal reflux disease.
AB  - Gastro-oesphageal reflux disease results primarily from the loss of an effective
      antireflux barrier, which forms a mechanical barrier against the retrograde
      movement of gastric content. This review describes the technique of performing a
      transoral incisionless fundoplication with the EsophyX(r) device. Transoral
      incisionless fundoplication reconfigures the tissue so as to establish serosa-to
      serosa plications which include the muscular layers, and construct 3-5 cm long
      valves 200-300 degrees  in circumference. The steps of the technique, as well as
      complications and their management are described in detail, and a recent
      literature review is also provided. At present, available prospective cohort
      studies indicate that transoral incisionless fundoplication using the EsophyX(r)
      device may be effective in approximately half PPI-responsive gastro-oesphageal
      reflux disease for up to 3 years' follow-up, without troublesome procedure
      related persistent side effects.

PMID- 22622204
TI  - Curcumin induces autophagy to protect vascular endothelial cell survival from
      oxidative stress damage.
AB  - Our study first proposed that curcumin could protect human endothelial cells from
      the damage caused by oxidative stress via autophagy. Furthermore, our results
      revealed that curcumin causes some novel cellular mechanisms that promote
      autophagy as a protective effect. Pretreatment with curcumin remarkably improves
      the survival of human umbilical vein endothelial cells (HUVECs) from H 2O 2
      induced viability loss, which specifically evokes an autophagic response. Exposed
      to H 2O 2, curcumin-treated HUVECs upregulate the level of microtubule-associated
      protein 1 light chain 3-II (LC3-II), the number of autophagosomes, and the
      degradation of p62. We show that this compound promotes BECN1 expression and
      inhibits the phosphatidylinositol 3-kinase (PtdIns3K)-AKT-mechanistic target of
      rapamycin (MTOR) signaling pathway. Curcumin can also reverse FOXO1 (a mediator
      of autophagy) nuclear localization along with causing an elevated level of
      cytoplasmic acetylation of FOXO1 and the interaction of acetylated FOXO1 and
      ATG7, under the circumstance of oxidative stress. Additionally, knockdown of
      FOXO1 by shRNA inhibits not only the protective effects that curcumin induced,
      but the autophagic process, from the quantity of LC3-II to the expression of
      RAB7. These results suggest that curcumin induces autophagy, indicating that
      curcumin has the potential for use as an autophagic-related antioxidant for
      prevention and treatment of oxidative stress. These data uncover a brand new
      protective mechanism involving FOXO1 as having a critical role in regulating
      autophagy in HUVECs, and suggest a novel role for curcumin in inducing a
      beneficial form of autophagy in HUVECs, which may be a potential multitargeted
      therapeutic avenue for the treatment of oxidative stress-related cardiovascular
      diseases.

PMID- 22622205
TI  - How closely do institutional review boards follow the common rule?
AB  - PURPOSE: To determine how closely institutional review board (IRB) discussions
      reflect the ethical criteria specified in the Common Rule federal regulations.
      METHOD: Between November 2006 and July 2009, the authors observed, audio
      recorded, transcribed, and coded protocol reviews from 20 IRB meetings at 10
      leading academic medical centers. They also reviewed each of the applications
      discussed to identify the Common Rule criteria-(1) risk minimization, (2)
      risk/benefit comparison, (3) equitable subject selection, (4) informed consent,
      (5) data monitoring to ensure safety, (6) privacy protection and confidentiality,
      and (7) protection of vulnerable subjects-that were both relevant to the study
      and not adequately addressed in the application. They then determined if the IRB
      addressed each of the relevant and not-discussed Common Rule criteria in their
      discussions. RESULTS: IRBs made no mention of many of the Common Rule criteria
      that required their discussion-In 17/82 (21%) reviews, they failed to address
      risk minimization; in 52/91 (57%), risk/benefit comparison; in 31/52 (60%),
      equitable subject selection; in 32/59 (54%), data monitoring; in 13/52 (25%),
      privacy and confidentiality; and in 7/55 (13%), protection of vulnerable
      populations. However, they discussed informed consent in 102/104 (98%) reviews
      and raised questions about, or requested changes about, informed consent for
      92/104 (88%) protocols. CONCLUSIONS: These findings suggest that essential
      elements of human subjects protection are not implemented uniformly across IRBs.
      Although not directly addressing this issue, the current proposed changes to the
      Common Rule offer an opportunity to improve, in general, the effectiveness of
      IRBs to protect human subjects.

PMID- 22622206
TI  - Institutional review board community members:  who are they, what do they do, and
      whom do they represent?
AB  - PURPOSE: The roles of nonaffiliated and nonscientific institutional review board
      (IRB) members at academic medical centers have received some attention, but
      questions remain-Who are they, what do they do, and whom, if anyone, do they
      represent? METHOD: The author interviewed 46 IRB chairs, directors,
      administrators, and members in 2007-2009. He contacted the leadership of 60 IRBs
      (every fourth one in the list of the top 240 institutions by National Institutes
      of Health funding), interviewed IRB leaders from 34 of these institutions, then
      recruited 7 additional members from these IRBs to interview. RESULTS: Regular IRB
      members often called these individuals community members and were confused as to
      who these members were, or should be, and whether they did, or should, represent
      anyone and, if so, whom. IRBs encountered challenges in finding, training, and
      retaining these community members. Tensions emerged because nonscientific
      members, by definition, have no scientific training, so they have difficulty
      understanding key aspects of protocols, making them feel unempowered to
      contribute to reviews. IRBs varied in how much they encouraged these members to
      participate, in what ways, and with what success. CONCLUSIONS: At academic
      medical centers, IRBs struggled with how to view, choose, employ, and retain
      nonaffiliated and nonscientific members, and they varied widely in these regards.
      Some IRBs had these members review entire protocols, others only limited parts
      (particularly reading consent forms for comprehension), pro forma. Yet, at times,
      these members' input proved very important. These findings have critical
      implications for policy, practice, and research.

PMID- 22622207
TI  - Perspective:  beyond counting hours:  the importance of supervision,
      professionalism, transitions of care, and workload in residency training.
AB  - The medical education community's conversations about residents' duty hours have
      long focused solely on the number of those hours. In July 2011, the Accreditation
      Council for Graduate Medical Education (ACGME) enacted its most recent iteration
      of standards regarding duty hours. Those standards, as well as a 2008 Institute
      of Medicine report, look beyond the quantity of duty hours to address their
      quality as well. Indeed, the majority of the 2011 ACGME standards specify
      requirements for the qualitative components of residents' working and learning
      environments, including supervision of residents; professionalism, personal
      responsibility, and patient safety; transitions of care; and clinical
      responsibilities (including workload). The authors believe that focusing on these
      qualitative (rather than quantitative) components of the resident's working and
      learning environment provides the greatest promise for balancing patient care
      with resident education, thus optimizing the safety and effectiveness of both.
      For each of the four qualitative components that the authors discuss (enhancing
      supervision, nurturing professionalism and personal responsibility, ensuring safe
      transitions of care, and optimizing workloads and cognitive loads), they offer
      agendas for faculty development, educational program planning, and research.
      Thus, the authors call on the medical education community to expand its
      discussion beyond counting duty hours to focus on these critical issues that
      ensure quality resident education and patient care and to implement necessary
      strategies to address them.

PMID- 22622208
TI  - Perspective:  research misconduct:  the search for a remedy.
AB  - Research misconduct-fabrication, falsification, and plagiarism-is an insidious
      problem in the scientific community today with the capacity to harm science,
      scientists, and the public. Federal agencies require that research trainees
      complete a course designed to deter such behavior, but the author could find no
      evidence to suggest that this effort has been effective. In fact, research shows
      that most cases of misconduct continue to go unreported.The author conducted a
      detailed examination of 146 individual Office of Research Integrity reports from
      1992 to 2003 and determined that these acts of misconduct were the results of
      individual psychological traits and the circumstances in which the researchers
      found themselves. Therefore, a course in research misconduct, such as is now
      federally mandated, should not be expected to have a significant effect. However,
      a course developed specifically for support staff, who currently do not receive
      such training, might prove effective.Improving the quality of mentoring is
      essential to meaningfully deal with this issue. Therefore, the quality of
      mentorship should be a factor in the evaluation of training grants for funding.
      In addition, mentors should share responsibility for their trainees' published
      work. The whistleblower can also play a significant role in this effort. However,
      the potential whistleblower is deterred by a realistic fear of retaliation.
      Therefore, institutions must establish policies that acknowledge the
      whistleblower's contribution to the integrity of science and provide truly
      effective protection from retaliation. An increase in whistleblowing activity
      would provide greater, earlier exposure of misconduct and serve as a deterrent.

PMID- 22622209
TI  - Public health physician specialty training in Canada and the United States.
AB  - Today's interconnected world has produced a distinct need for physician
      specialists in public health and preventive medicine. As the industrialized world
      confronts aging populations, rising health care costs, and a growing epidemic of
      chronic disease, it is clear that the focus of health care must become more
      preventive than curative.Although public health and preventive medicine exists in
      various forms worldwide, the literature has not yet examined different national
      strategies for postgraduate medical training in this unique specialty. This
      examination of present-day public health physician training in Canada and the
      United States represents a first step in addressing this gap.Using a standardized
      template for review, the authors compare key aspects of public health physician
      specialty training in both countries, including the definition and scope of the
      specialty; oversight and location of training; length of postgraduate training;
      specific clinical, academic, and practicum requirements; residency program
      funding; availability of residency positions; certification; and the roles of
      specialists.The authors explore similarities and differences between public
      health physician specialists in Canada and the United States in an effort to
      highlight training improvements for incorporation into each country's training
      program and to identify potential avenues of collaboration and cooperation across
      the border.

PMID- 22622210
TI  - Preparing medical students to facilitate lifestyle changes with obese patients: 
      a systematic review of the literature.
AB  - PURPOSE: Doctors will increasingly encounter opportunities to support obese
      patients in lifestyle change efforts, but the extent to which medical schools
      prepare their students for this challenge is unknown. Further, despite evidence
      indicating theory-based techniques are effective in facilitating patients'
      behavioral changes, the methods taught to medical students and the means of
      content delivery are unclear. The authors reviewed the literature to investigate
      how effective educational interventions are in preparing medical students to
      facilitate lifestyle changes with obese patients. METHOD: The authors
      systematically searched Excerpta Medica (EMBASE), PsycINFO, MEDLINE, and Scopus
      for educational interventions on obesity management for medical students
      published in English between January 1990 and November 2010 and matching PICOS
      (Population, Interventions, Comparators, Outcomes, Study design) inclusion
      criteria. RESULTS: Results of a narrative synthesis are presented. Of 1,680
      studies initially identified, 36 (2%) full-text articles were reviewed, and 12
      (1%) were included in the final dataset. Eleven (92%) of these studies had
      quantitative designs; of these, 7 (64%) did not include control groups. Nine
      (75%) of the 12 studies were atheoretical, and 4 (33%) described behavior
      management strategies. Despite positive reported outcomes regarding intervention
      evaluations, procedures to control for bias were infrequently reported, and
      conclusions were often unsupported by evidence. CONCLUSIONS: Evidence from this
      systematic review revealed data highly susceptible to bias; thus, intervention
      efficacy could not be determined. Additionally, evidence-based strategies to
      support patients' obesity-related behavior changes were not applied to these
      studies, and thus it remains unknown how best to equip medical students for this
      task.

PMID- 22622211
TI  - Internal medicine trainees' views of training adequacy and duty hours
      restrictions in 2009.
AB  - PURPOSE: To gauge internal medicine (IM) trainees' perceptions regarding aspects
      of their inpatient rotations, including supervision, educational opportunities,
      the perceived effect of duty hours regulations on quality of patient care, the
      causes of medical errors, and sleep. METHOD: The authors analyzed the results of
      questionnaires administered to trainees following the October 2009 in-training
      examinations (ITE). RESULTS: Of the 21,768 IM trainees in postgraduate years 1
      through 3 who took the IM-ITE, 18,272 (83.9%) responded. The majority of these
      trainees (87.7%) reported that supervision was adequate, and nearly half (46.3%)
      reported insufficient or minimal time to participate in learning activities. Two
      thirds or more thought that specific work regulations such as limited shift
      length and more time off after nights and extended shifts would at least
      "occasionally," if not "usually" or "always," improve patient care. IM trainees
      at least "occasionally" attributed errors to workload (68.8% of respondents),
      fatigue (66.9%), inexperience or lack of knowledge (61.0%), incomplete handoffs
      (60.2%), and insufficient ancillary staff (53.5%). IM trainees' sleep hours were
      limited during extended and overnight shifts. CONCLUSIONS: IM trainees agree that
      limited educational opportunities are the weakest part of the average inpatient
      rotation. Few have complaints about the adequacy of supervision. These trainees'
      optimism regarding the positive influence of potential work hours restrictions on
      patient care and their views of likely causes of medical errors suggest the need
      for innovative patient care schedules and education curricula.

PMID- 22622212
TI  - Careers in medicine at Vanderbilt University School of Medicine: an innovative
      approach to specialty exploration and selection.
AB  - Research on resident attrition rates suggests that medical students would benefit
      from more comprehensive career advising programs during medical school.
      Responding to this need, students and administrators at the Vanderbilt University
      School of Medicine (Vanderbilt) introduced a broad Careers in Medicine (CiM)
      program in 2005 to complement the CiM resources offered by the Association of
      American Medical Colleges (AAMC). In this article, the authors detail the
      Vanderbilt CiM program's four core components: career-related events, an elective
      course, specialty interest groups, and career advising. The authors discuss the
      program's implementation and its student-led organizational structure, and they
      provide a critical assessment of important lessons learned. Using data from
      internal satisfaction surveys and the AAMC's Medical School Graduation
      Questionnaire (GQ), they demonstrate the success of Vanderbilt's career
      counseling efforts. According to recent GQ data, Vanderbilt ranks above the U.S.
      medical school average on graduating students' ratings of overall satisfaction
      with career services and of the usefulness of key programming. The authors
      present this description of the Vanderbilt CiM model as a framework for other
      medical schools to consider adopting or adapting as they explore options for
      expanding their own career counseling services.

PMID- 22622213
TI  - Why are a quarter of faculty considering leaving academic medicine? A study of
      their perceptions of institutional culture and intentions to leave at 26
      representative U.S. medical schools.
AB  - PURPOSE: Vital, productive faculty are critical to academic medicine, yet studies
      indicate high dissatisfaction and attrition. The authors sought to identify key
      personal and cultural factors associated with intentions to leave one's
      institution and/or academic medicine. METHOD: From 2007 through early 2009, the
      authors surveyed a stratified random sample of 4,578 full-time faculty from 26
      representative U.S. medical schools. The survey asked about advancement,
      engagement, relationships, diversity and equity, leadership, institutional values
      and practices, and work-life integration. A two-level, multinomial logit model
      was used to predict leaving intentions. RESULTS: A total of 2,381 faculty
      responded (52%); 1,994 provided complete data for analysis. Of these, 1,062 (53%)
      were female and 475 (24%) were underrepresented minorities in medicine. Faculty
      valued their work, but 273 (14%) had seriously considered leaving their own
      institution during the prior year and 421 (21%) had considered leaving academic
      medicine altogether because of dissatisfaction; an additional 109 (5%) cited
      personal/family issues and 49 (2%) retirement as reasons to leave. Negative
      perceptions of the culture-unrelatedness, feeling moral distress at work, and
      lack of engagement-were associated with leaving for dissatisfaction. Other
      significant predictors were perceptions of values incongruence, low institutional
      support, and low self-efficacy. Institutional characteristics and personal
      variables (e.g., gender) were not predictive. CONCLUSIONS: Findings suggest that
      academic medicine does not support relatedness and a moral culture for many
      faculty. If these issues are not addressed, academic health centers may find
      themselves with dissatisfied faculty looking to go elsewhere.

PMID- 22622214
TI  - How can educators use simulation applications to teach and assess surgical
      judgment?
AB  - Surgical simulation applications have been largely limited to the acquisition and
      assessment of technical skills. Current teaching and assessment of surgical
      judgment is nonsystematic and prone to error. Interest in methods to enhance the
      acquisition and assessment of knowledge-based (judgment) skills for
      intraoperative decision making has led to the application of cognitive task
      analysis (CTA) and human error assessment to facilitate this process. CTA-based
      delineation of the steps and hazards of a surgical procedure creates a structured
      process to teach and assess expert surgical judgment and improves trainees'
      operative planning, hazard recognition, error prevention, and error recovery when
      coupled with low-fidelity, synthesized simulation models for open and
      laparoscopic surgery. Web-based simulation applications facilitate curricular
      learning (rules-guided skills), allow cognitive rehearsal of procedures, and are
      accessible independent of location and time. Simulation applications that
      facilitate the assessment and learning of expert intraoperative judgment should
      include a consensus-derived outline based on CTA of the operative steps and
      potential points of risk for each surgical procedure; the ability to detect the
      situational awareness of the performer and the options considered to avoid error
      at critical steps; an assessment (scoring) of options considered or attempted;
      immediate evaluation feedback to inform improved performance; and a program of
      deliberate practice in which progressively more challenging scenarios can be
      introduced, based on the trainee's demonstrated skills. High-fidelity simulators
      currently lack these essential components, and future simulation-assisted
      teaching and assessment of surgical judgment skills are likely to employ low
      fidelity simulators coupled to Web-based instruction.

PMID- 22622215
TI  - Fully aligned academic health centers:  a model for 21st-century job creation and
      sustainable economic growth.
AB  - Alignment is the degree to which component parts of academic health centers
      (AHCs) work cohesively. Full alignment allows AHCs to act quickly and cohesively
      toward common goals and to take advantage of opportunities that present
      themselves, particularly where collaboration is essential. Maryland's two major
      AHCs-University of Maryland Medicine (UMM) and Johns Hopkins Medicine (JHM)-have
      experienced periods of significant misalignment during each of their histories.
      Their most recent periods of misalignment caused significant negative economic
      and academic impacts. However, the process of realigning their clinical and
      research missions has not only given them a renewed economic vigor but has also
      paid significant dividends for the state of Maryland, helping it weather the
      current recession much better than other regions of the country. The two AHCs'
      continued economic success during the recession has led Maryland lawmakers to
      increasingly seek out their expertise in attempts to stimulate economic
      development. Indeed, UMM, JHM, and other fully aligned AHCs have shown that they
      can be powerful economic engines and offer a model of job growth and economic
      development in the 21st century.

PMID- 22622217
TI  - Perspective:  a culture of respect, part 1:  the nature and causes of
      disrespectful behavior by physicians.
AB  - A substantial barrier to progress in patient safety is a dysfunctional culture
      rooted in widespread disrespect. The authors identify a broad range of
      disrespectful conduct, suggesting six categories for classifying disrespectful
      behavior in the health care setting: disruptive behavior; humiliating, demeaning
      treatment of nurses, residents, and students; passive-aggressive behavior;
      passive disrespect; dismissive treatment of patients; and systemic disrespect.At
      one end of the spectrum, a single disruptive physician can poison the atmosphere
      of an entire unit. More common are everyday humiliations of nurses and physicians
      in training, as well as passive resistance to collaboration and change. Even more
      common are lesser degrees of disrespectful conduct toward patients that are taken
      for granted and not recognized by health workers as disrespectful.Disrespect is a
      threat to patient safety because it inhibits collegiality and cooperation
      essential to teamwork, cuts off communication, undermines morale, and inhibits
      compliance with and implementation of new practices. Nurses and students are
      particularly at risk, but disrespectful treatment is also devastating for
      patients. Disrespect underlies the tensions and dissatisfactions that diminish
      joy and fulfillment in work for all health care workers and contributes to
      turnover of highly qualified staff. Disrespectful behavior is rooted, in part, in
      characteristics of the individual, such as insecurity or aggressiveness, but it
      is also learned, tolerated, and reinforced in the hierarchical hospital culture.
      A major contributor to disrespectful behavior is the stressful health care
      environment, particularly the presence of "production pressure," such as the
      requirement to see a high volume of patients.

PMID- 22622216
TI  - Interprofessional education:  a review and analysis of programs from three
      academic health centers.
AB  - The past decade witnessed momentum toward redesigning the U.S. health care system
      with the intent to improve quality of care. To achieve and sustain this change,
      health professions education must likewise reform to prepare future practitioners
      to optimize their ability to participate in the new paradigm of health care
      delivery. Recognizing that interprofessional education (IPE) is gaining momentum
      as a crucial aspect of health care professions training, this article provides an
      introduction to IPE programs from three different academic health centers, which
      were developed and implemented to train health care practitioners who provide
      patient-centered, collaborative care. The three participating programs are
      briefly described, as well as the processes and some lessons learned that were
      critical in the process of adopting IPE programs in their respective
      institutions. Critical aspects of each program are described to allow comparison
      of the critical building blocks for developing an IPE program. Among those
      building blocks, the authors present information on the planning processes of the
      different institutions, the competencies that each program aims to instill in the
      graduates, the snapshot of the three curricular models, and the assessment
      strategies used by each institution. The authors conclude by providing details
      that may provide insight for academic institutions considering implementation of
      IPE programs.

PMID- 22622218
TI  - How and why internal medicine clerkship directors use locally developed, faculty
      written examinations:  results of a national survey.
AB  - PURPOSE: To describe how and why internal medicine clerkship directors (CDs) use
      locally developed, faculty-written (LFW) examinations. METHOD: In 2009, the
      Clerkship Directors in Internal Medicine conducted an annual, online,
      confidential survey of its 107 U.S. and Canadian institutional members, including
      questions about LFW examinations. Data were analyzed using descriptive statistics
      and coding of free text. RESULTS: Sixty-nine of 107 members (64.5%) responded.
      The National Board of Medical Examiners (NBME) examination was administered by
      93% (63/68), LFW examinations were used by 33% (22/67), and both types were used
      by 22% (17/67)-compared with 85%, 36%, and 12% in 2005. LFW examinations were
      frequently created by the CD alone (9/22; 41%) and consisted of one test (12/22;
      52.2%), but some schools gave two (6/22; 26.1%), three (2/22; 8.6%), or four or
      more (3/22; 13%). Multiple-choice examinations were most common (26/38; 68.4%),
      followed by short-answer (8/38; 21.1%) and essay (4/38; 10.5%). Most were graded
      using preestablished criteria; half required a minimum passing score (60% most
      common). LFW exams were most commonly 5% to 10% of the total grade. Only a
      minority of CDs reported having reliability estimates or a control group for
      their exams. Most (70%) reported using LFW exams to cover content felt to be
      underrepresented by the NBME. CONCLUSIONS: Findings strongly suggest that a
      minority of internal medicine CDs use LFW examinations, mostly to measure
      achievement not assessed by the NBME. However, validity evidence is not
      consistently being gathered, which may limit judgments based on exam results.

PMID- 22622219
TI  - Perspective:  a culture of respect, part 2:  creating a culture of respect.
AB  - Creating a culture of respect is the essential first step in a health care
      organization's journey to becoming a safe, high-reliability organization that
      provides a supportive and nurturing environment and a workplace that enables
      staff to engage wholeheartedly in their work. A culture of respect requires that
      the institution develop effective methods for responding to episodes of
      disrespectful behavior while also initiating the cultural changes needed to
      prevent such episodes from occurring. Both responding to and preventing
      disrespect are major challenges for the organization's leader, who must create
      the preconditions for change, lead in establishing and enforcing policies, enable
      frontline worker engagement, and facilitate the creation of a safe learning
      environment.When disrespectful behavior occurs, it must be addressed consistently
      and transparently. Central to an effective response is a code of conduct that
      establishes unequivocally the expectation that everyone is entitled to be treated
      with courtesy, honesty, respect, and dignity. The code must be enforced fairly
      through a clear and explicit process and applied consistently regardless of rank
      or station.Creating a culture of respect requires action on many fronts: modeling
      respectful conduct; educating students, physicians, and nonphysicians on
      appropriate behavior; conducting performance evaluations to identify those in
      need of help; providing counseling and training when needed; and supporting
      frontline changes that increase the sense of fairness, transparency,
      collaboration, and individual responsibility.

PMID- 22622220
TI  - Behavior change counseling curricula for medical trainees:  a systematic review.
AB  - PURPOSE: Unhealthy behaviors contribute to half of U.S. deaths. However,
      physicians lack sufficient skill in counseling patients to change behaviors.
      Characterizing effective published curricular interventions for behavior change
      counseling for medical trainees would inform educators toward improved training.
      METHOD: The authors conducted a systematic literature search of studies published
      between 1965 and 2011 evaluating curricula on behavior change counseling for
      medical trainees. Included studies described behavior change counseling, teaching
      interventions for medical trainees, and assessment of interventions. The authors
      extracted eligible articles, rated outcomes for learners and patients using
      Kirkpatrick's hierarchy, and determined study quality. RESULTS: Of 2,788
      identified citations, 109 met inclusion criteria. Most studies were performed in
      the United States (98), 93 at a single institution, and 81 in primary care
      settings. Curricular topics for counseling included smoking (67 studies),
      nutrition (30), alcohol/drug use (26), and exercise (22). Although most studies
      did not include theoretical frameworks, 39 used the Transtheoretical Model of
      Change. Sixty-two studies involved eight or fewer hours of curricular time, and
      51 spanned four or fewer weeks. The studies with highest-level outcomes and
      quality employed multiple curricular techniques and included practice of
      counseling techniques in either simulated or actual clinical settings.
      CONCLUSIONS: Existing literature suggests that trainees learn behavior change
      counseling through active, realistic practice and implementation of reminder and
      feedback systems within actual clinical practice settings. Multiinstitutional
      medical education research on methods of teaching behavior change counseling that
      influence patients' health outcomes are needed to ensure trainees' clinical
      competence and improve patient care.

PMID- 22622221
TI  - Anticipated consequences of the 2011 duty hours standards:  views of internal
      medicine and surgery program directors.
AB  - PURPOSE: To assess internal medicine (IM) and surgery program directors' views of
      the likely effects of the 2011 Accreditation Council for Graduate Medical
      Education duty hours regulations. METHOD: In fall 2010, investigators surveyed IM
      and surgery program directors, assessing their views of the likely impact of the
      2011 duty hours standards on learning environment, workload, education
      opportunities, program administration, and patient outcomes. RESULTS: Of 381 IM
      program directors, 287 (75.3%) responded; of 225 surgery program directors, 118
      (52.4%) responded. Significantly more surgeons than internists indicated that the
      new regulations would likely negatively impact learning climate, including
      faculty morale and residents' relationships (P < .001). Most leaders in both
      specialties (80.8% IM, 80.2% surgery) felt that the regulations would likely
      increase faculty workload (P = .73). Both IM (82.2%) and surgery (96.6%) leaders
      most often rated, of all education opportunities, first-year resident clinical
      experience to be adversely affected (P < .001). Respondents from both specialties
      indicated that they will hire more nonphysician/midlevel providers (59.5% IM,
      89.0% surgery, P < .001) and use more nonteaching services (66.8% IM, 70.1%
      surgery, P = .81). Respondents expect patient safety (45.1% IM, 76.9% surgery, P
      < .001) and continuity of care (83.6% IM across all training levels, 97.5%
      surgery regarding first-year residents) to decrease. CONCLUSIONS: IM and surgery
      program directors agree that the 2011 duty hours regulations will likely
      negatively affect the quality of the learning environment, workload, education
      opportunities, program administration, and patient outcomes. Careful evaluation
      of actual impact is important.

PMID- 22622222
TI  - A standards-based, peer-reviewed teaching award to enhance a medical school's
      teaching environment and inform the promotions process.
AB  - The authors provide the rationale, design, and description of a unique teaching
      award that has enhanced Baylor College of Medicine's teaching environment and
      become highly valued by the promotions and tenure (P&T) committee in determining
      a faculty member's readiness for promotion. This award is self-nominating and
      standards based. The primary purpose for development of the award was to provide
      the Baylor community and the P&T committee a method to understand and value the
      scholarship of teaching to the same degree that they understand and value the
      scholarship of discovery.The authors also present results from an internal
      evaluation of the program that included a survey and interviews. Between the
      inception of the award in 2001 and the internal review conducted in 2010, the
      award could have had an influence on the promotion of 130 of the recipients. Of
      the 130, 88 (65.6%) received this award before gaining their current rank (chi
      (1) = 16.3, P < .001). Stakeholders, including department chairs and members of
      the P&T committee, agreed that this award is valuable to those seeking promotion.
      Individual recipients stated that the award is good for the institution by
      encouraging reflection on teaching; increasing the recognition, importance, and
      value of teaching; encouraging the improvement of teaching skills; and providing
      a better understanding to others about what medical teachers really do. Of the
      214 open-ended responses to survey questions of award recipients, more than half
      the comments were about the value of the award and its positive effect on
      promotion.

PMID- 22622223
TI  - Psychological maltreatment in relation to substance use problem severity among
      youth.
AB  - OBJECTIVES: Research has demonstrated that experiences of childhood maltreatment
      are prevalent in the life histories of youth with substance use problems;
      however, most of this research has focused on sexual or physical abuse. The
      purpose of the current study was to extend the scope of previous investigations
      to include psychological maltreatment experiences, examining the extent to which
      emotional abuse and emotional neglect predict substance use problem severity
      among youth. The current study also sought to examine whether a cumulative model
      fit the data, in which the experience of multiple forms of maltreatment would be
      related most strongly to severity of substance use problems, or whether there was
      a distinct effect of psychological maltreatment. METHODS: Data were collected
      through self-report questionnaires from 216 youth (144 males, 72 females)
      entering an outpatient treatment program for youth with substance use concerns.
      RESULTS: Results indicated that, when considering all forms of abuse together,
      only emotional abuse and emotional neglect emerged as significant predictors of
      substance use problem severity. Furthermore, the association between
      psychological maltreatment and substance use problem severity was unaltered by
      the consideration of concurrent experiences of interpersonal violence.
      CONCLUSIONS: The results of the current study are consistent with those of a body
      of research describing the detrimental effects of psychological maltreatment. The
      findings have potential implications for the development and provision of trauma
      informed youth substance use treatment services. The findings suggest that
      attending to the sequelae of psychological maltreatment may be important in
      assisting these youth in achieving successful treatment outcomes.

PMID- 22622224
TI  - Exploring the role of child sexual abuse and posttraumatic stress disorder
      symptoms in gay and bisexual men reporting compulsive sexual behavior.
AB  - OBJECTIVES: Compulsive sexual behavior (CSB) is an impairing yet understudied
      clinical phenomenon. The experience of child sexual abuse (CSA) has been
      implicated as an etiological factor in the development of some cases of CSB
      (Kuzma & Black, 2008); however, research regarding the role of CSA and related
      psychopathology in CSB symptomatology has been limited in the literature. The
      present study aimed to examine the uniqueness of the association of CSA with CSB
      as compared to other experiences of child maltreatment; the role of posttraumatic
      stress disorder (PTSD) symptomatology in CSB symptoms for individuals reporting
      CSA; and clinical differences between individuals with and without histories of
      CSA. METHODS: Hypotheses were tested using data from a sample of 182 gay and
      bisexual men reporting CSB symptoms. RESULTS: CSA prevalence was high in the
      tested sample (39%). CSA severity was a unique predictor of CSB symptoms, above
      child physical and emotional abuse, and poly-victimization status was not
      significantly related to CSB symptoms. Contrary to hypotheses, PTSD symptoms did
      not significantly mediate the role of CSA severity, although PTSD symptoms
      explained additional variance in CSB symptoms, with the final model accounting
      for over a quarter of the variance in CSB symptoms (27%). Finally, men with a
      history of CSA reported more CSB, depressive, and anxious symptoms than those
      without a history of CSA. CONCLUSIONS: Findings from the present study support
      the hypothesis that CSA may be uniquely related to CSB symptoms, above other
      forms of child maltreatment, and indicate that men with a CSA history are likely
      to present more severe clinical comorbidities. Clinical implications and future
      research directions are discussed.

PMID- 22622225
TI  - Stress responses and decision making in child protection workers faced with high
      conflict situations.
AB  - INTRODUCTION: The assessment of children at risk of abuse and neglect is a
      critical societal function performed by child protection workers in situations of
      acute stress and conflict. Despite efforts to improve the reliability of risk
      assessments through standardized measures, available tools continue to rely on
      subjective judgment. The goal of this study was to assess the stress responses of
      child protection workers and their assessments of risk in high conflict
      situations. METHODS: Ninety-six child protection workers participated in 2
      simulated scenarios, 1 non-confrontational and 1 confrontational. In each
      scenario, participants conducted a 15-minute interview with a mother played by a
      specially trained actor. Following the interview, the workers completed 2 risk
      assessment measures used in the field at the time of the study. Anxiety was
      measured by the State-Trait Anxiety Inventory at baseline and immediately
      following the completion of each interview. Physiological stress as measured by
      salivary cortisol was obtained at baseline as well as 20 and 30 minutes after the
      start of each interview. RESULTS: Participants demonstrated significant stress
      responses during the 1st scenario, regardless of whether the interview was
      confrontational or not. During the second scenario, the participants did not
      exhibit significant cortisol responses, however the confrontational interview
      elicited greater subjective anxiety than the non-confrontational scenario. In the
      first scenario, in which the workers demonstrated greater stress responses, risk
      assessment scores were higher on one risk assessment tool for the confrontational
      scenario than for the non-confrontational scenario. CONCLUSION: The results
      suggest that stress responses in child protection workers appear to be influenced
      by the novelty of a situation and by a parent's demeanor during interviews. Some
      forms of risk assessment tools appear to be more strongly associated than other
      with the workers' subjective and physiological stress responses. This merits
      further research to determine which aspects of risk assessment tools are
      susceptible to the emotional elements of intake interviews.

PMID- 22622226
TI  - [Stereotactic intracranial radiotherapy: dose prescription].
AB  - The aim of this article was the study of the successive steps permitting the
      prescription of dose in stereotactic intracranial radiotherapy, which includes
      radiosurgery and fractionated stereotactic radiotherapy. The successive steps
      studied are: the choice of stereotactic intracranial radiotherapy among the
      therapeutic options, based on curative or palliative treatment intent, then the
      selection of lesions according to size/volume, pathological type and their number
      permitting the choice between radiosurgery or fractionated stereotactic
      radiotherapy, which have the same methodological basis. Clinical experience has
      determined the level of dose to treat the lesions and limit the irradiation of
      healthy adjacent tissues and organs at risk structures. The last step is the
      optimization of the different parameters to obtain a safe compromise between the
      lesion dose and healthy adjacent structures. Study of dose-volume histograms,
      coverage indices and 3D imaging permit the optimization of irradiation. For
      lesions close to or included in a critical area, the prescribed dose is planned
      using the inverse planification method. Implementation of the successively
      described steps is mandatory to insure the prescription of an optimized dose. The
      whole procedure is based on the delineation of the lesion and adjacent healthy
      tissues. There are sometimes difficulties to assess the delineation and the
      volume of the target, however improvement of local control rates and reduction of
      secondary effects are the proof that the totality of the successive procedures
      are progressively improved. In practice, stereotactic intracranial radiotherapy
      is a continually improved treatment method, which constantly benefits from
      improvements in the choice of indications, imaging, techniques of irradiation,
      planification/optimization methodology and irradiation technique and from data
      collected from prolonged follow-up.

PMID- 22622227
TI  - Oxytricha as a modern analog of ancient genome evolution.
AB  - Several independent lines of evidence suggest that the modern genetic system was
      preceded by the 'RNA world' in which RNA genes encoded RNA catalysts. Current
      gaps in our conceptual framework of early genetic systems make it difficult to
      imagine how a stable RNA genome may have functioned and how the transition to a
      DNA genome could have taken place. Here we use the single-celled ciliate,
      Oxytricha, as an analog to some of the genetic and genomic traits that may have
      been present in organisms before and during the establishment of a DNA genome.
      Oxytricha and its close relatives have a unique genome architecture involving two
      differentiated nuclei, one of which encodes the genome on small, linear
      nanochromosomes. While its unique genomic characteristics are relatively modern,
      some physiological processes related to the genomes and nuclei of Oxytricha may
      exemplify primitive states of the developing genetic system.

PMID- 22622228
TI  - Updating the RNA polymerase CTD code: adding gene-specific layers.
AB  - The carboxyl-terminal domain (CTD) of RNA polymerase (pol) II comprises multiple
      tandem repeats with the consensus sequence Tyr(1)-Ser(2)-Pro(3)-Thr(4)-Ser(5)
      Pro(6)-Ser(7) that can be extensively and reversibly modified in vivo. CTD
      modifications orchestrate the interplay between transcription and processing of
      mRNA. Although phosphorylation of Ser2 (Ser2P) and Ser5 (Ser5P) residues has been
      described as being essential for the expression of most pol II-transcribed genes,
      recent findings highlight gene-specific effects of newly discovered CTD
      modifications. Here, we incorporate these latest findings in an updated review of
      the currently known elements that contribute to the CTD code and how it is
      recognized by proteins involved in transcription and RNA maturation. As
      modification of the CTD has a major impact on gene expression, a better
      understanding of the CTD code is integral to the understanding of how gene
      expression is regulated.

PMID- 22622230
TI  - Genetic basis of blood pressure and hypertension.
AB  - Blood pressure (BP) is a complex trait regulated by an intricate network of
      physiological pathways involving extracellular fluid volume homeostasis, cardiac
      contractility and vascular tone through renal, neural or endocrine systems.
      Untreated high BP, or hypertension (HTN), is associated with increased mortality,
      and thus a better understanding of the pathophysiological and genetic
      underpinnings of BP regulation will have a major impact on public health.
      However, identifying genes that contribute to BP and HTN has proved challenging.
      In this review we describe our current understanding of the genetic architecture
      of BP and HTN, which has accelerated over the past five years primarily owing to
      genome-wide association studies (GWAS) and the continuing progress in uncovering
      rare gene mutations, epigenetic markers and regulatory pathways involved in the
      physiology of BP. We also look ahead to future studies characterizing novel
      pathways that affect BP and HTN and discuss strategies for translating current
      findings to the clinic.

PMID- 22622231
TI  - Re-evaluating visual and auditory dominance through modality switching costs and
      congruency analyses.
AB  - Competition between the senses can lead to modality dominance, where one sense
      influences multi-modal processing to a greater degree than another. Modality
      dominance can be influenced by task demands, speeds of processing, contextual
      influence and practice. To resolve previous discrepancies in these factors, we
      assessed modality dominance in an audio-visual paradigm controlling for the first
      three factors while manipulating the fourth. Following a uni-modal task in which
      auditory and visual processing were equated, participants completed a pre
      practice selective attention bimodal task in which the congruency relationship
      and task-relevant modality changed across trials. Participants were given
      practice in one modality prior to completing a post-practice selective attention
      bimodal task similar to the first. The effects of practice were non-specific as
      participants were speeded post-practice relative to pre-practice. Congruent
      stimuli relative to incongruent stimuli, also led to increased processing
      efficiency. RT data tended to reveal symmetric modality switching costs whereas
      the error rate data tended to reveal asymmetric modality switching costs in which
      switching from auditory to visual processing was particularly costly. The data
      suggest that when a number of safeguards are put in place to equate auditory and
      visual responding as far as possible, evidence for an auditory advantage can
      arise.

PMID- 22622229
TI  - Epigenetics of major psychosis: progress, problems and perspectives.
AB  - Understanding the origins of normal and pathological behavior is one of the most
      exciting opportunities in contemporary biomedical research. There is increasing
      evidence that, in addition to DNA sequence and the environment, epigenetic
      modifications of DNA and histone proteins may contribute to complex phenotypes.
      Inherited and/or acquired epigenetic factors are partially stable and have
      regulatory roles in numerous genomic activities, thus making epigenetics a
      promising research path in etiological studies of psychiatric disease. In this
      article, we review recent epigenetic studies examining the brain and other
      tissues, including those from individuals with schizophrenia (SCZ) and bipolar
      disorder (BPD). We also highlight heuristic aspects of the epigenetic theory of
      psychiatric disease and discuss the future directions of psychiatric epigenetics.

PMID- 22622232
TI  - The influence of stimulus-set size on developmental changes in cognitive control
      and conflict adaptation.
AB  - Cognitive control abilities substantially improve from early childhood to
      adulthood. The primary aim of this study was to examine the influence of stimulus
      set size on developmental changes in cognitive control abilities such as task
      switching, interference control, and conflict adaptation. We assumed that a small
      stimulus set used in a task-switching paradigm would induce stronger task
      stimulus priming that might increase the need for control, thereby amplifying age
      differences in cognitive control abilities. Therefore, we compared task-switching
      performance in a group of participants responding to a small stimulus-set (N=4)
      with a group responding to a large stimulus-set (N=96) in three age groups:
      kindergarten children (4.1-6.0 years of age), elementary school children (6.1-9.0
      years of age), and young adults (21.0-28.0 years of age) on conflicting vs. non
      conflicting trials (interference control) and following conflicting vs. non
      conflicting trials (conflict adaptation). Results on the basis of error rates
      support the view that a small stimulus-set size during task switching (i.e.,
      larger task-stimulus priming) increases the need for control as we found (a)
      worse conflict adaptation on task-repetition trials only for small but not for
      large set sizes and (b) larger interference costs under small than large set-size
      condition for elementary school children as compared with young adults.
      Kindergarten children were less sensitive to the set-size manipulation and showed
      major problems in interference control while being in a task-switching situation,
      even if no actual task switch was required, possibly reflecting their inability
      to represent complex higher-order task rules.

PMID- 22622233
TI  - Beneficial cardiac effects of cicletanine in conscious rabbits with metabolic
      syndrome.
AB  - BACKGROUND AND PURPOSE: High-fat diet and consequent metabolic syndrome (MS) can
      lead to elevated risk for cardiac arrhythmias. This preclinical study was to
      investigate if cicletanine (CIC) could produce cardioprotective effects in
      conscious rabbits exhibiting the main symptoms of MS. METHODS: NZW rabbits that
      had undergone an 8-week-long cholesterol-enriched diet (1.5%) were instrumented
      with a pacemaker electrode and randomly assigned into 3 groups according to the
      oral treatment of either CIC (50 mg.kg) or sotalol (25 mg.kg) and their placebo
      b.i.d. over 5 days. Study groups were subjected to either "arrhythmia challenge"
      by programmed electrical stimulation in the "Arrhythmogenesis" study (N = 54) or
      global myocardial ischemia by rapid pacing in the "Ventricular Overdrive Pacing
      induced Myocardial Ischemia" study (N = 18). The antiarrhythmic effect was
      evaluated by the establishment of the incidence of programmed electrical
      stimulation-induced arrhythmias. Proarrhythmia indicators (eg, QTc, Tpeak-Tend)
      were also measured to assess the cardiac safety profile of CIC. To evaluate the
      background of antiarrhythmic effect, cardiac cyclic nucleotide (cyclic 3',5'
      guanosine monophosphate [cGMP], cyclic 3',5'-adenosine monophosphate [cAMP]) and
      nitric oxide content were determined. The antiischemic effect was characterized
      by change of intracavital ST segment. RESULTS: Cicletanine treatment
      significantly decreased the incidence of ventricular arrhythmias, increased
      cardiac cGMP and nitric oxide content and reduced cardiac cAMP level. Cicletanine
      did not modify significantly QTc and Tpeak-Tend interval. The ST-segment change
      in response to rapid pacing was reduced significantly by CIC. (P < 0.05).
      CONCLUSIONS: Cicletanine exerts beneficial cardiac effects in rabbits with
      symptoms of MS, which may be of influence with regard to the clinical application
      of the drug.

PMID- 22622234
TI  - Roles of 7-ketocholesterol on the homeostasis of intracellular cholesterol level.
AB  - Atherosclerotic plaque contains materials, such as cholesterol, oxysterols, cell
      debris, modified fatty acids, and infiltrated cells. Among them, cholesterol is
      the major component in plaque. Cholesterol is known to originate from the influx
      of extracellular materials, but this explanation is not enough for the
      cholesterol accumulation observed in atherosclerotic plaque. This study examined
      the origins of cholesterols in plaques. The main focus was to determine if the
      intracellular cholesterol levels are affected by oxysterols in human vascular
      smooth muscle cells. The results showed that the cholesterol levels increased in
      response to a 7-ketocholesterol (7K)-treatment in a dose-dependent manner. Eight
      enzymes involved in cholesterol biosynthesis were examined. Among them, squalene
      epoxidase (SQLE) was increased by 7K but not by 7alpha-hydroxycholesterol, 27
      hydroxycholesterol (27OH-chol), or cholesterol. The 7K-induced SQLE expression
      was suppressed in the presence of the enzyme inhibitor SB203580 but not by UO126
      and SP600125. The SQLE immunoreactivity was detected in the atherosclerotic
      plaque of the aortic roots from apoE mice. In addition, 7K increased the
      cholesterol level and SQLE expression in murine bone marrow-derived macrophages.
      This suggests that 7K increases the intracellular cholesterol level through an
      elevation of SQLE expression, which might affect the progress of cholesterol
      accumulation in the atherosclerotic lipid core.

PMID- 22622235
TI  - Nitrite and nitrate: from bench to bedside.

PMID- 22622236
TI  - [Spinal root of accessory nerve shwannoma: about a new case].
AB  - BACKGROUND: The accessory nerve schwannoma localized in spinal canal is extremely
      rare; only nine cases have been reported in the literature until now. We report a
      new case of schwannoma at the spinal root of accessory nerve. OBSERVATION: A
      young woman aged 30 had a high cervical spinal cord compression with respiratory
      problems. At admission, magnetic resonance imaging (MRI) showed a tumor
      compressing the spinal cord at C2 to the foramen magnum. The tumor was removed
      successfully and its origin from the left accessory nerve was confirmed
      peroperatively. CONCLUSION: Although schwannoma of the accessory nerve is
      exceptional, this entity should be considered as a differential diagnosis with
      the other tumors of the foramen magnum.

PMID- 22622237
TI  - A multi-shear perfusion bioreactor for investigating shear stress effects in
      endothelial cell constructs.
AB  - Tissue engineering research is increasingly relying on the use of advanced
      cultivation technologies that provide rigorously-controlled cell
      microenvironments. Herein, we describe the features of a micro-fabricated Multi
      Shear Perfusion Bioreactor (MSPB) designed to deliver up to six different levels
      of physiologically-relevant shear stresses (1-13 dyne cm(-2)) to six cell
      constructs simultaneously, during a single run. To attain a homogeneous fluid
      flow within each construct, flow-distributing nets photo-etched with a set of
      openings for fluid flow were placed up- and down-stream from each construct.
      Human umbilical vein endothelial cells (HUVECs) seeded in alginate scaffolds
      within the MSPB and subjected to three different levels of shear stress for 24 h,
      responded accordingly by expressing three different levels of the membranal
      marker Intercellular Adhesion Molecule 1 (ICAM-1) and the phosphorylated
      endothelial nitric oxide synthetase (eNOS). A longer period of cultivation, 17 d,
      under two different levels of shear stress resulted in different lengths of cell
      sprouts within the constructs. Collectively, the HUVEC behaviour within the
      different constructs confirms the feasibility of using the MSPB system for
      simultaneously imposing different shear stress levels, and for validating the
      flow regime in the bioreactor vessel as assessed by the computational fluid
      dynamic (CFD) model.

PMID- 22622238
TI  - N-propionyl-4-S-cysteaminylphenol induces apoptosis in B16F1 cells and mediates
      tumor-specific T-cell immune responses in a mouse melanoma model.
AB  - BACKGROUND: N-propionyl-4-S-cysteaminylphenol (NPr-4-S-CAP) is selectively
      incorporated into melanoma cells and degrades them. However, it remains unclear
      whether NPr-4-S-CAP can induce cell death associated with the induction of host
      immune responses and tumor suppression in vivo. OBJECTIVE: To examine the
      molecular mechanism of NPr-4-S-CAP-mediated cytotoxicity toward melanoma cells
      and to test whether NPr-4-S-CAP can suppress transplanted primary and secondary
      B16F1 melanomas. METHODS: Cytotoxicity and apoptosis of melanoma cells were
      assessed by cell counting, flow cytometry, and detection of reactive oxygen
      species (ROS) and apoptotic molecules. NPr-4-S-CAP-associated host immunity was
      studied using a B16F1 mouse melanoma model through the application of CD4- and
      CD8-specific antibodies and tetramer assay. RESULTS: NPr-4-S-CAP suppressed
      growth of pigmented melanoma cells associated with an increase of intracellular
      ROS, activation of caspase 3 and DNA fragmentation, suggesting that NPr-4-S-CAP
      mediated ROS production, eliciting apoptosis of melanoma cells. Growth of
      transplanted B16F1 melanomas was inhibited after the consecutive intratumoral
      injections of NPr-4-S-CAP, and the tumor growth after rechallenge of B16F1 was
      significantly suppressed in the treated mice. This suppression occurred when the
      treated mice were given the anti-CD4 antibody, but not the anti-CD8 antibody.
      Tetramer assay demonstrated increased TYRP-2-specific CD8(+) T cells in the lymph
      node and spleen cells prepared from NPr-4-S-CAP-treated B16F1-bearing mice.
      CONCLUSIONS: These suggest that NPr-4-S-CAP induces apoptosis in melanoma cells
      through ROS production and generates CD8(+) cell immunity resulting in the
      suppression of rechallenged B16F1 melanoma.

PMID- 22622239
TI  - Association between degenerative spondylolisthesis and spinous process fracture
      after interspinous process spacer surgery.
AB  - BACKGROUND CONTEXT: Spinous process fracture is a recognized complication
      associated with interspinous process spacer (IPS) surgery. Although occasionally
      identified by plain radiographs, computed tomography (CT) appears to identify a
      higher rate of such fractures. Although osteoporotic insufficiency fracture is
      considered a contraindication for IPS surgery, a formal risk factor analysis for
      this complication has not previously been reported. PURPOSE: To identify risk
      factor(s) associated with early spinous process fracture after IPS surgery. STUDY
      DESIGN/SETTING: Prospective cohort study of 39 consecutive patients with lumbar
      stenosis and neurogenic claudication undergoing IPS surgery at a single
      institution. METHODS: Patients underwent preoperative dual-energy X-ray
      absorptiometry (DXA) scans, lumbar spine CT, and plain radiographs.
      Postoperatively, patients underwent repeat CT imaging within 6 months of surgery
      and serial radiographs at 2 weeks, 6 weeks, 3 months, 6 months, and 1 year.
      Preoperative CT scans were analyzed by calculating average Hounsfield units for a
      1 cm(2) area of the midsagittal reconstructed image for four separate locations:
      midvertebral body, subcortical bone subjacent to the superior margin of the
      midspinous process, subcortical bone above the inferior margin of the midspinous
      process, and the midspinous process. RESULTS: Thirty-eight patients underwent IPS
      surgery at a total of 50 levels (38 L4-L5, 12 L3-L4; 26 one-level, 12 two-level).
      One patient underwent laminectomy at index surgery and was excluded from the
      analysis. Implants included 34 titanium X-STOP (Medtronic, Memphis, TN, USA), 8
      polyaryletheretherketone X-STOP (Medtronic, Memphis, TN, USA), and 8 Aspen (Lanx,
      Broomfield, CO, USA) devices. Eleven spinous process fractures were identified by
      CT in 11 patients (22.0% of levels). No fractures were apparent on plain
      radiographs. The rate of spondylolisthesis observed on preoperative radiographs
      was 100% (11 of 11) among patients with fractures compared with 33.3% (9 of 27)
      of patients without fracture (p=.0001). Overall, 21 of 39 patients in this series
      had spondylolisthesis, and the rate of fracture in this group was 52%. Among
      patients without spondylolisthesis, the fracture rate was 0%. A trend was
      observed toward decreased DXA lumbar spine and hip T-scores among fracture
      patients versus nonfracture patients (0.2 +/- 1.7 vs. 0.8 +/- 1.7; p=.389; -1.1
      +/- 1.4 vs. -0.3 +/- 1.4; p=.201), but these differences were not significant.
      Similarly, bone density based on CT measurements at four different locations
      revealed a trend toward decreased density among fracture patients, but these
      differences were not significant. CONCLUSIONS: Degenerative spondylolisthesis
      appears strongly associated with the occurrence of spinous process fracture after
      IPS surgery. There is a trend toward increased fracture risk in patients with
      decreased bone mineral density as measured by both DXA scan and CT-based volume
      averaging of Hounsfield units, but osteoporosis appears to be a relatively weaker
      risk factor. The association between spondylolisthesis and fracture observed in
      this study may account for the relatively poorer outcome of IPS surgery in
      patients with spondylolisthesis that has been reported in previous series.

PMID- 22622240
TI  - Selective anion sensing by a ruthenium(II)-bipyridyl-functionalized tripodal
      tris(urea) receptor.
AB  - A tripodal tris(urea) ligand with 2,2'-bipyridyl (bpy) substituents (L) has been
      designed and synthesized, which coordinates with three equivalents of
      Ru(bpy)(2)Cl(2).2H(2)O, followed by treatment with NH(4)PF(6), to afford the
      anion receptor [(bpy)(6)Ru(3)L](PF(6))(6) (1). The anion-binding behavior of the
      ligand L and the Ru(II)-bpy functionalized receptor 1 toward different anions was
      investigated by (1)H NMR (for L and 1), fluorescence, and UV-vis spectroscopy
      (for 1). Both compounds showed selective recognition of SO(4)(2-) or H(2)PO(4)(-)
      ions in the 1:1 binding mode in the NMR studies. The Ru(II) complex 1 displayed
      the metal-to-ligand charge transfer emission at 600 nm, which was quenched on
      addition of the sulfate and dihydrogen phosphate ions. Quantitative fluorescence
      titration experiments were carried out and the stability constants (log K) of the
      complex 1 with SO(4)(2-) and H(2)PO(4)(-) ions were obtained to be 4.73 and 4.69
      M(-1) (1:1 binding mode), respectively.

PMID- 22622241
TI  - Endocytic processing of adeno-associated virus type 8 vectors for transduction of
      target cells.
AB  - We investigated the transduction of HEK293T cells permissive to adeno-associated
      virus serotype 8 (AAV8) to understand the mechanisms underlying its endocytic
      processing. Results showed that AAV8 enters cells through clathrin-mediated
      endocytosis followed by trafficking through various endosomal compartments.
      Interestingly, compared to the relatively well-characterized AAV2, a distinct
      involvement of late endosomes was observed for AAV8 trafficking within the target
      cell. AAV8 particles were also shown to exploit the cytoskeleton network to
      facilitate their transport within cells. Moreover, the cellular factors involved
      during endosomal escape were examined by an in vitro membrane permeabilization
      assay. Our data demonstrated that an acidic endosomal environment was required
      for AAV2 penetration through endosomal membranes and that the cellular
      endoprotease furin could promote AAV2 escape from the early endosomes. In
      contrast, these factors were not sufficient for AAV8 penetration through
      endosomal membranes. We further found that the ubiquitin-proteasome system is
      likely involved in the intracellular transport of AAV8 to nucleus. Taken
      together, our data have shed some light on the intracellular trafficking pathways
      of AAV8, which, in turn, could provide insight for potentializing AAV-mediated
      gene delivery.

PMID- 22622243
TI  - At-risk mental states: possible clinical and theoretical developments.

PMID- 22622242
TI  - The reinforcement threshold for nicotine as a target for tobacco control.
AB  - BACKGROUND: Cigarette smoking represents an enormous public health problem
      worldwide that leads to over 5 million deaths per year. The gradual reduction of
      the nicotine content of cigarettes below the threshold that is required to
      develop addiction is one strategy that might substantially reduce the number of
      addicted smokers and prevent adolescents from becoming addicted to nicotine
      (Benowitz and Henningfield, 1994). While the potential public health benefits of
      this approach are enormous, the guiding concepts and relevant empirical evidence
      needed to support the implementation of a nicotine reduction policy require a
      critical examination. METHODS: The purpose of this paper is to briefly review the
      current concepts and research regarding nicotine reduction while also discussing
      the utility of the addictive threshold for nicotine in this approach. The
      accurate determination of the nicotine addiction threshold presents some
      conceptual challenges as there is a lack of consensus on how to best measure
      nicotine addiction. This difficulty can impede the progress for developing a
      science-based tobacco control policy. As an alternative, the nicotine
      reinforcement threshold is a relatively clear concept, and well-accepted methods
      and criteria are available to measure nicotine reinforcement. RESULTS: However,
      there are many gaps in our current knowledge concerning the nicotine
      reinforcement threshold in humans. The threshold for nicotine reinforcement
      remains to be determined in controlled settings using different populations of
      current or potential tobacco users. In addition, the value of the nicotine
      reinforcement threshold in predicting tobacco use in real-world settings needs to
      be examined. The results of such studies will determine the potential utility of
      the estimated threshold for nicotine reinforcement in developing science-based
      tobacco control policies.

PMID- 22622244
TI  - [Searching for psychosocial endophenotypes in schizophrenia:  the innovative role
      of brain imaging].
AB  - Schizophrenia is a disease with heterogeneous features and often a disabling
      longitudinal outcome. In order to achieve a better understanding of the disease,
      a detailed characterization and definition of symptomatology, social functioning
      and cognitive performance of patients is required. Imaging techniques may allow
      to identify measurable markers of different subgroups of patients, who share
      common clinical course and, probably, a similar hereditary pathway. The review
      offers a description of cross-sectional, predictive and longitudinal studies on
      the relationship between biological, clinical and psychosocial features of
      patients with schizophrenia. Patients with a more severe and disabling course of
      illness present larger ventricles, smaller prefrontal, temporal and occipital
      cortices and smaller subcortical regions such as basal ganglia, the thalamus and
      limbic areas. These alterations are predictive of a worse prognosis, as observed
      in predictive and longitudinal studies, both on chronic and first episode
      patients. The detection of more homogenous groups of patients with schizophrenia
      will help neurobiological research progress in this field. Furthermore, patients
      with similar clinical and biological features could undergo more tailored
      therapeutic and rehabilitative strategies.

PMID- 22622245
TI  - [Competitive employment in schizophrenia: clinical and neuropsychological 
      correlates and quality of life].
AB  - AIM: To investigate the relationships among psychopatology, cognitive
      functioning, quality of life and competitive employment in patients with stable
      schizophrenia. MATERIALS AND METHODS: We recruited 143 consecutive outpatients
      with stable schizophrenia, divided into 2 groups (unemployed and competitive
      employed subjects). A clinical and a neuropsychological assessments were
      performed. The differences between the two groups were tested using chi-square
      test for categorical variables and one-way analysis of variance (ANOVA) for
      continuous variables. Variables significantly different between the two groups of
      subjects were analyzed using a logistic regression with a backward stepwise
      procedure to assess their independent contribution to competitive employment in
      the two patients' groups. RESULTS: The two groups of patients had similar
      demographic characteristics, except education. Negative symptoms (PANSS-N) and
      general psychopathology (PANSS-G) were significantly less severe in the group of
      patients with a competitive employment, that also showed higher scores at the
      Quality of Life Scale (QLS) and higher scores on verbal memory/learning (CVLT)
      and attentive functions (Stroop test). Binary logistic regression showed that
      education, verbal memory/learning and quality of life, were significantly
      associated with the presence of competitive employment. DISCUSSION: Our findings
      confirmed the importance of cognitive function in obtaining competitive
      employment and highlighted the independent role of quality of life and education
      on occupational functioning in schizophrenia.

PMID- 22622246
TI  - [The language disorders in schizophrenia in neurolinguistic and psycholinguistic
      perspectives].
AB  - The descriptive psychopathology has classically equated the language with the
      formal aspects of thought. Recent developments in experimental and clinical
      research have emphasized the study of the language as a specific communicative
      ability. Within the framework of cognitive neuropsychology, the development of
      innovative research models, such as those based on the mentalizing ability, has
      allowed to formulate new hypotheses on the pathogenetic aspects of schizophrenia.
      Furthermore, mentalizing ability appears to be a basic skill for the pragmatic
      dimension of language. The author, after a brief description of the methods of
      investigation of neurolinguistics and psycholinguistics, presents a review of
      recent studies obtained by consulting the PubMed and PsycINFO databases. Finally,
      he focuses on the relationship between research findings and issues related to
      clinical practice.

PMID- 22622247
TI  - Schizophrenia and obsessive-compulsive disorder: from comorbidity to schizo
      obsessive disorder.
AB  - Current genetic, neurobiological, clinical-descriptive and pharmacological data
      about obsessive-compulsive symptoms (OCS) and/or obsessive-compulsive disorder
      (OCD) in schizophrenia hypothesize that schizophrenia combined with OCD is more
      than a mere comorbidity. To prove this hypothesis, "dimensional diagnosis", based
      on the identification of a dysfunctional area common to different clinical cases,
      should replace "categorical diagnosis", that focuses on discrete parameters that
      define specific disorders. It is our hope that the DSM-V will make reference to
      principles based on psychopathological "spectra" because these reflect the
      integration of pharmacotherapeutic, descriptive and etiopathogenetic aspects
      (genotypes common to various disorders, temperamental predispositions,
      neurobiological and chemical alteration). These three aspects explain how
      obsessive phenomena can develop into delusional phenomena.

PMID- 22622248
TI  - [Challenges in the early detection of psychosis in children and adolescents].
AB  - The early detection and treatment of persons at-risk for psychosis is currently
      regarded a promising strategy in fighting the devastating consequences of
      psychotic disorders. The two current at-risk approaches, i.e., the "ultra high
      risk" and the "basic symptom" criteria, were mainly developed on adult samples.
      Initial evidence suggests, however, that they cannot simply be applied to
      children and adolescents. For ultra high risk criteria, there is indication of
      some attenuated psychotic symptoms being potentially non-specific in adolescents
      and of brief limited intermittent symptoms being difficult to clinically classify
      in children when observable behavioral correlates are missing. For basic
      symptoms, too, only preliminary indication of their usefulness in children and
      adolescents exists. Since developmental peculiarities in the assessment of basic
      symptoms should be considered, a child and youth version of the Schizophrenia
      Proneness Instrument (SPI-CY) was developed. In conclusion, research on the
      clinical-prognostic validity of the at-risk criteria and their potential adoption
      to the special needs of children and adolescents is needed. If a Prodromal Risk
      Syndrome for Psychosis or Attenuated Psychotic Symptoms Syndrome will be included
      into DSM-V, it has to be highlighted that its suitability for children and
      adolescents is only insufficiently known.

PMID- 22622249
TI  - [Facial Action Coding System (FACS): an instrument for the objective evaluation
      of facial expression and its potential applications to the study of
      schizophrenia].
AB  - INTRODUCTION: Affective flattening and the consequent anomalous expression of
      emotions are considered as key elements of the negative symptoms of
      schizophrenia. The purpose of this work is to assess how a survey instrument
      based on objective evaluation of emotional facial expressiveness (FACS) and a
      method of elicitation of emotions (film clips) can provide psychopathological
      manifestations about schizophrenia. METHODS: Relevant literature was identified
      through a search of Medline, PsychInfo and PubMed. Search terms included:
      "elicitation of emotions", "facial action coding system" and "schizophrenia". The
      research was limited to English-language publications and studies conducted
      exclusively in humans. RESULTS: The overall evaluation of the studies analyzed in
      this work show that the FACS is a useful tool to highlight specific clinical
      characteristics of schizophrenic patients with significant deficits in the
      expression and recognition of emotions, such as the status of hospitalization,
      the age of onset, the treatment with antipsychotic drugs, the SANS, SAPS and BPRS
      scores. CONCLUSIONS: Even if we have preliminary and incomplete data, the FACS
      and the elicitation of emotions through film clips can give an original
      contribution to the development of knowledge on pathophysiological events and
      interpretive models of schizophrenia.

PMID- 22622250
TI  - [Spectral analysis of Heart Rate Variability in psychiatric patients: autonomic 
      nervous system evaluation in psychotic, anxiety and depressive disorders].
AB  - AIM: The aim of this study was to test the primary hypothesis of altered Heart
      Rate Variability (HRV) and heart rate in a sample of patients with mental
      disorders and the secondary hypothesis of normalization of HRV values as a result
      of clinical improvement. METHODS: The study was conducted on a sample of 90
      patients with psychotic, anxiety and mood disorders. Each patient was subjected
      to detection of HRV and heart rate via a photoplethysmographic sensor and
      evaluated with rating scales based on the specific disorder. The parameters
      detected in the sample were compared with a control group of healthy subjects.
      RESULTS: There were no significant differences of cardiac autonomic modulation
      between the group of patients in whom is possible exclude the drug influence and
      the control group; significantly lower values of HRV parameters in the group of
      patients with drug influence, and especially in subgroup of psychotic patients,
      compared to controls, are, instead, detected. The study also shows a significant
      increase in heart rate as a common feature in mental disorders, regardless of
      treatment. Clinical improvement appears to promote the normalization of the
      variability in patients with high DS of tachogram. DISCUSSION: The study suggests
      a potential increased risk of cardiovascular mortality in patients, as evidenced
      by the increased values of heart rate, regardless of drug treatment. This risk is
      even more pronounced in psychotic patients in drug treatment because of the
      simultaneous significant reduction of HRV parameters.

PMID- 22622251
TI  - [Evidence on the key role of the metabotrobic glutamatergic receptors in the
      pathogenesis of schizophrenia: a "breakthrough" in pharmacological treatment].
AB  - The metabotropic glutamate receptors (mGluRs) are expressed pre- and post
      synaptically throughout the nervous system where they serve as modulators of
      synaptic transmission and neuronal excitability. The glutamatergic system is
      involved in a wide range of physiological processes in the brain, and its
      dysfunction plays an important role in the etiology and pathophysiology of
      psychiatric disorders, including schizophrenia. This paper reviews the
      neurodevelopmental origin and genetic susceptibility of schizophrenia relevant to
      NMDA receptor neurotransmission, and discusses the relationship between NMDA
      hypofunction and different domains of symptom in schizophrenia as well as
      putative treatment modality for the disorder. mGlu receptors have been
      hypothesizes as attractive therapeutic targets for the development of novel
      interventions for psychiatric disorders. Group II of mGlu receptors are of
      particular interest because of their unique distribution and the regulatory roles
      they have in neurotransmission. The glutamate hypothesis of schizophrenia
      predicts that agents that restore the balance in glutamatergic neurotransmission
      will ameliorate the symptomatology associated with this illness. Development of
      potent, efficacious, systemically active drugs will help to address the
      antipsychotic potential of these novel therapeutics. This review will discuss
      recent progress in elucidating the pharmacology and function of group II
      receptors in the context of current hypotheses on the pathophysiology of
      schizophrenia and the need for new and better antipsychotics.

PMID- 22622252
TI  - [Use of cannabis and psychopathological risk in onset psychosis].
AB  - AIM: The aim of the study is to assess the correlations between cannabis use and
      psychopathological features, disorder severity and global functioning in subjects
      with onset psychosis (schizophrenic and bipolar psychosis) and at risk mental
      state. MATERIALS AND METHODS: Sixty-seven consecutive subjects with diagnosis of
      bipolar spectrum disorder (N=49), schizophrenic spectrum disorder (N=5) and at
      risk mental state (N=13) were recruited from the SMILE (Service for Monitoring
      and early Intervention Looking at the fight against the onset of mental Even
      psychological youths' suffering). All subjects were assessed with the Self Report
      Symptom Inventory-90 (SCL-90), the Global Assessment of Functioning scale (GAF)
      and Clinical Global Impressions-Severity (CGI-S). Moreover, they were assessed
      for the cannabis use in the last month. RESULTS: The total sample was splitted in
      two groups: Group 1 of cannabis use subjects (N=30) and Group 2 of no cannabis
      use subjects (N=37). Group 1 subjects showed significant higher scores at
      psychoticism SCL-90 dimension and at CGI-S than Group 2 subjects. The higher
      scores at anger/hostility and psychoticism SCL-90 dimensions and at CGI-S seem to
      be discriminant features of Group 1 cannabis use subjects. CONCLUSIONS: The data
      reported suggest that cannabis use assessment in onset psychosis (bipolar and
      schizophrenic onset) and at risk mental state could add clinical information to
      the psychopathological and diagnostic description. Such information should be
      ''incorporated'' in the treatment choice model and outcome prediction assessment.

PMID- 22622253
TI  - [Catatonia and neuroleptic malignant syndrome: two disorders on a same  spectrum?
      Three case reports].
AB  - AIM: The authors present the cases of three bipolar patients who developed
      Neuroleptic Malignant Syndrome (NMS) after antipsychotic treatment, both typical
      and atypical, focusing on relationship between NMS and catatonia. METHODS: In all
      three cases, administration of antipsychotics has been stopped at once, when
      fever and autonomic disturbances occurred. A supportive therapy (including
      rehydration, electrolyte restoration and blood pressure aids, together with
      antipyretics, antibiotics and anticoagulants) was prescribed in order to
      stabilize general conditions. Every patient started then Electroconvulsive
      Therapy (ECT) in combination with benzodiazepines. RESULTS: High risk of
      complications and lethal outcome, associated with NMS, were successfully reduced
      by the tempestive adoption of a supportive care, while combination between ECT
      and BDZ was effective in resolution of clinical picture. DISCUSSIONS; These cases
      may provide further evidences about hypothesis of catatonia and NMS as disorders
      on the same spectrum. In one patient, NMS occurred overlapping with a previous
      catatonic state, while two others exhibited catatonic features after resolution
      of NMS. However, catatonic symptoms arose or worsened with administration of
      antipsychotics, supporting hypothesis of neuroleptic-induced catatonia as a step
      of progressive development of NMS. Our experience also confirms efficacy and
      safety of ECT in combination with BDZ as treatment of NMS and residual catatonia.

PMID- 22622254
TI  - Guanidine catalyzed aerobic reduction: a selective aerobic hydrogenation of
      olefins using aqueous hydrazine.
AB  - An efficient aerobic reduction of olefins, internal as well as terminal, is
      developed using guanidine as an organocatalyst. A remarkable chemoselectivity in
      reduction has been demonstrated in the presence of a variety of functional groups
      and protective groups and a selective reduction of a terminal olefin in the
      presence of an internal olefin is revealed.

PMID- 22622255
TI  - Selective autophagy in the aid of plant germination and response to nutrient
      starvation.
AB  - Selective autophagy, mediated by Atg8 binding proteins, has not been extensively
      studied in plants. Plants possess a large gene family encoding multiple isoforms
      of the Atg8 protein. We have recently reported the identification of two new,
      closely homologous Arabidopsis thaliana plant proteins that bind the Arabidopsis
      Atg8f protein isoform. These two proteins are specific to plants and have no
      homologs in nonplant organisms. The expression levels of the genes encoding these
      proteins are elevated during carbon starvation and also during late stages of
      seed development. Exposure of young seedlings to carbon starvation induces the
      production of a newly identified compartment decorated by these Atg8-binding
      proteins. This compartment dynamically moves along the endoplasmic reticulum
      membrane and is also finally transported into the vacuole. Enhanced or suppressed
      expression of these Atg8-binding proteins respectively enhances or suppresses
      seed germination under suboptimal germination conditions, indicating that they
      contribute to seed germination vigor.

PMID- 22622256
TI  - Unexpected formation of stannolanes and trigonal bipyramidal tin complexes by
      radical cyclization reaction.
AB  - Optically active stannolanes and trigonal bipyramidal pentacoordinated tin
      complexes were readily prepared by radical cyclization of N-propargylated chiral
      aza-Morita-Baylis-Hillman adducts induced by Bu(3)SnH. A translocated radical
      through the cyclization attacked the Bu(3)Sn group in an S(H)2 manner.

PMID- 22622257
TI  - Aggregatibacter aphrophilus pyogenic liver abscess in an immunocompetent young
      woman.
AB  - Aggregatibacter aphrophilus (formerly Haemophilus aphrophilus/paraphrophilus) is
      a small Gram-negative coccobacillus with fastidious growth requirements. It is a
      normal commensal of the human oropharynx and upper respiratory tract, and it can
      infrequently cause invasive human diseases, including bone and joint infections
      and subacute infective endocarditis. Cases of liver abscess caused by
      Aggregatibacter aphrophilus have been sparsely recorded in the English-language
      literature, but have not yet been reported in Taiwan. Here we present a case of
      Aggregatibacter aphrophilus pyogenic liver abscess in an immunocompetent young
      woman. She recovered uneventfully after repeated percutaneous abscess aspiration
      and antibiotic treatment for 5 weeks.

PMID- 22622258
TI  - "Excited delirium syndrome": is it a cause of death?
AB  - Excited delirium syndrome (EDS) has become a controversial and vexing forensic
      issue due to its association with restraint and sudden unexpected death. Although
      some authorities and jurisdictions recognised EDS as a cause of death there is no
      consensus among the medical community in this regard. The overlapping nature of
      the spectrum of antemortem behaviours and signs with many natural disease
      processes complicates this issue further. We describe two deaths which initially
      presented as EDS-like behaviour during restraint. In the first case, the deceased
      was travelling on a long distance flight when he died while in the custody of air
      cabin crew. The autopsy revealed the cause of death as air travel-related
      pulmonary thromboembolism. Acute alcoholic intoxication, nicotine withdrawal,
      hypoxia due to acute pulmonary thromboembolism, and hypobaric environment in the
      air plane cabin appeared as the potential reasons for EDS-like behaviour. In the
      second case, the deceased died while in the custody of immigration officials. At
      autopsy the cause of death turned out to be tense pericardial effusion due to
      fibrinous pericarditis. In this case, hypoperfusion of the brain following
      systemic hypotension as a result of cardiac tamponade associated with pericardial
      effusion likely led to the EDS-like behaviour. Clinicopathologic correlation in
      these two cases would strongly suggest EDS as the cause of death, had the
      decedents not had fatal anatomical causes of death. This alerts the forensic
      pathologist that not all the individuals dying with signs and symptoms of EDS
      during restraint are accounted for EDS as the immediate cause of death.

PMID- 22622259
TI  - Pediatric maxillofacial surgery.

PMID- 22622260
TI  - Differential sensitivities to tyrosine kinase inhibitors in NSCLC harboring EGFR
      mutation and ALK translocation.
AB  - Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase
      (ALK) translocations in non-small cell lung cancer (NSCLC) are mutually
      exclusive. However, several exceptional cases harboring both genetic alterations
      have been reported. In this study, a total of 444 patients with lung
      adenocarcinoma were examined for their EGFR and ALK status at Seoul National
      University Hospital between July 2008 and September 2011. EGFR mutations and ALK
      translocations were detected in 228 (51.4%) and 34 (7.7%) patients, respectively.
      Four patients (0.9%) had both genetic alterations and three underwent curative
      surgery. One patient who received both EGFR tyrosine kinase and ALK inhibitors,
      separately showed an objective response to the ALK inhibitor alone. Considering
      our and previous studies, patients harboring both EGFR mutation and ALK
      translocation showed differential sensitivities to both targeted therapies,
      suggesting a variable dependence on EGFR and ALK oncogenes.

PMID- 22622261
TI  - On the periodic dynamics of a class of time-varying delayed neural networks via
      differential inclusions.
AB  - This paper investigates the periodic dynamics of a general class of time-varying
      delayed neural networks with discontinuous right-hand sides. By employing the
      topological degree theory in set-valued analysis, differential inclusions theory
      and Lyapunov-like approach, we perform a thorough analysis of the existence,
      uniqueness and global exponential stability of the periodic solution for the
      neural networks. Especially, some sufficient conditions are derived to guarantee
      the existence, uniqueness and global exponential stability of the equilibrium
      point for the autonomous systems corresponding to the non-autonomous neural
      networks. Furthermore, the global convergence of the output and the convergence
      in finite time of the state are also discussed. Without assuming the boundedness
      or monotonicity of the discontinuous neuron activation functions, the obtained
      results improve and extend previous works on discontinuous or continuous neural
      network dynamical systems. Finally, two numerical examples are provided to show
      the applicability and effectiveness of our main results.

PMID- 22622262
TI  - Modeling learned categorical perception in human vision.
AB  - A long standing debate in cognitive neuroscience has been the extent to which
      perceptual processing is influenced by prior knowledge and experience with a
      task. A converging body of evidence now supports the view that a task does
      influence perceptual processing, leaving us with the challenge of understanding
      the locus of, and mechanisms underpinning, these influences. An exemplar of this
      influence is learned categorical perception (CP), in which there is superior
      perceptual discrimination of stimuli that are placed in different categories.
      Psychophysical experiments on humans have attempted to determine whether early
      cortical stages of visual analysis change as a result of learning a
      categorization task. However, while some results indicate that changes in visual
      analysis occur, the extent to which earlier stages of processing are changed is
      still unclear. To explore this issue, we develop a biologically motivated neural
      model of hierarchical vision processes consisting of a number of interconnected
      modules representing key stages of visual analysis, with each module learning to
      exhibit desired local properties through competition. With this system level
      model, we evaluate whether a CP effect can be generated with task influence to
      only the later stages of visual analysis. Our model demonstrates that task
      learning in just the later stages is sufficient for the model to exhibit the CP
      effect, demonstrating the existence of a mechanism that requires only a high
      level of task influence. However, the effect generalizes more widely than is
      found with human participants, suggesting that changes to earlier stages of
      analysis may also be involved in the human CP effect, even if these are not
      fundamental to the development of CP. The model prompts a hybrid account of task
      based influences on perception that involves both modifications to the use of the
      outputs from early perceptual analysis along with the possibility of changes to
      the nature of that early analysis itself.

PMID- 22622263
TI  - Computational properties and convergence analysis of BPNN for cyclic and almost
      cyclic learning with penalty.
AB  - Weight decay method as one of classical complexity regularization methods is
      simple and appears to work well in some applications for backpropagation neural
      networks (BPNN). This paper shows results for the weak and strong convergence for
      cyclic and almost cyclic learning BPNN with penalty term (CBP-P and ACBP-P). The
      convergence is guaranteed under certain relaxed conditions for activation
      functions, learning rate and under the assumption for the stationary set of error
      function. Furthermore, the boundedness of the weights in the training procedure
      is obtained in a simple and clear way. Numerical simulations are implemented to
      support our theoretical results and demonstrate that ACBP-P has better
      performance than CBP-P on both convergence speed and generalization ability.

PMID- 22622264
TI  - Complex-valued autoencoders.
AB  - Autoencoders are unsupervised machine learning circuits, with typically one
      hidden layer, whose learning goal is to minimize an average distortion measure
      between inputs and outputs. Linear autoencoders correspond to the special case
      where only linear transformations between visible and hidden variables are used.
      While linear autoencoders can be defined over any field, only real-valued linear
      autoencoders have been studied so far. Here we study complex-valued linear
      autoencoders where the components of the training vectors and adjustable matrices
      are defined over the complex field with the L(2) norm. We provide simpler and
      more general proofs that unify the real-valued and complex-valued cases, showing
      that in both cases the landscape of the error function is invariant under certain
      groups of transformations. The landscape has no local minima, a family of global
      minima associated with Principal Component Analysis, and many families of saddle
      points associated with orthogonal projections onto sub-space spanned by sub
      optimal subsets of eigenvectors of the covariance matrix. The theory yields
      several iterative, convergent, learning algorithms, a clear understanding of the
      generalization properties of the trained autoencoders, and can equally be applied
      to the hetero-associative case when external targets are provided. Partial
      results on deep architecture as well as the differential geometry of autoencoders
      are also presented. The general framework described here is useful to classify
      autoencoders and identify general properties that ought to be investigated for
      each class, illuminating some of the connections between autoencoders,
      unsupervised learning, clustering, Hebbian learning, and information theory.

PMID- 22622265
TI  - Diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy.

PMID- 22622266
TI  - News from the Breath Analysis Summit 2011.
AB  - This special section highlights some of the important work presented at the
      Breath Analysis Summit 2011, which was held in Parma (Italy) from 11 to 14
      September 2011. The meeting, which was jointly organized by the International
      Association for Breath Research and the University of Parma, was attended by more
      than 250 delegates from 33 countries, and offered 34 invited lectures and 64
      unsolicited scientific contributions.   The summit was organized to provide a
      forum to scientists, engineers and clinicians to present their latest findings
      and to meet industry executives and entrepreneurs to discuss key trends, future
      directions and technologies available for breath analysis.  A major focus was on
      nitric oxide, exhaled breath condensate, electronic nose, mass spectrometry and
      newer sensor technologies. Medical applications ranged from asthma and other
      respiratory diseases to gastrointestinal disease, occupational diseases, critical
      care and cancer.  Most people identify breath tests with breathalysers used by
      police to estimate ethanol concentration in blood. However, breath testing has
      far more sophisticated applications. Breath analysis is rapidly evolving as a new
      frontier in medical testing for disease states in the lung and beyond. Every
      individual has a breath fingerprint-or 'breathprint'-that can provide useful
      information about his or her state of health. This breathprint comprises the many
      thousands of molecules that are expelled with each breath we exhale.  Breath
      research in the past few years has uncovered the scientific and molecular basis
      for such clinical observations. Relying on mass spectrometry, we have been able
      to identify many such unique substances in exhaled breath, including gases, such
      as nitric oxide (NO) and carbon monoxide (CO), and a wide array of volatile
      organic compounds. Exhaled breath also carries aerosolized droplets that can be
      collected as an exhaled breath condensate that contains endogenously produced non
      volatile compounds.   Breath analysis is now used to diagnose and monitor asthma,
      check for transplant organ rejection, detect lung cancer and test for
      Helicobacter pyloriinfection-and the list is growing. A major milestone in the
      scientific study of breath was marked in the 1970s when Linus Pauling
      demonstrated that there is more to exhaled breath than the classic gases of
      nitrogen, oxygen, carbon dioxide and water vapour-a lot more. Based on the gas
      liquid partition chromatography analysis, Pauling reported the presence of 250
      substances in exhaled breath. We now have the technology to test for any and all
      of these components. The field of breath analysis has made considerable advances
      in the 21st century and the utility of breath analysis in health care is
      advancing quickly. The science is rapidly expanding, the technology is improving
      and several new applications have been developed or are under commercial
      development.  Breath analysis may rely on both direct (on line) and indirect (off
      line) reading methods: in the on-line method, breath analysis is immediately
      available, whereas the use of indirect methods generally involves collecting and
      trapping the breath sample and subsequently transferring it to an analytical
      instrument for analysis.  Various kinds of breath samples have been used in
      biological monitoring, including mixed expired air and end expired air: end
      exhaled air represents the alveolar air concentration and mixed exhaled air
      represents the gas mixture coming from the dead space of the bronchial tree and
      the alveolar gas-exchange space.   Exhaled breath analysis is an area where the
      modern day advances in technology and engineering meet the ever expanding need in
      medicine for more sensitive, specific and non-invasive tests which makes this
      area a major front in the interface between medicine and engineering.   A major
      breakthrough over the past decade has been the increase in breath-based tests
      approved by the US Food and Drug Administration (FDA). Devices measuring common
      breath gases (oxygen, nitrogen, water vapour and CO(2)) in patient respiratory
      monitoring have served as a platform for technological growth in clinical breath
      testing applications. A few exhaled breath tests have demonstrated clinical
      utility and are in widespread use, and several FDA-approved devices are
      available. These widely used exhaled breath tests include detection of blood
      alcohol concentration and exhaled CO(2). Other clinical applications of exhaled
      breath analysis include testing for H. pylori infection, lactose intolerance,
      heart transplant rejection and, more recently, monitoring of airway inflammation
      by means of exhaled NO.  Examination of exhaled breath has the potential to
      change the existing routine approaches in human medicine. The rapidly developing
      new analytical and computer technologies along with novel, unorthodox ideas are
      prerequisites for future advances in this field.  Scientists who participated in
      the Breath Analysis Summit 2011 were invited to submit a full length paper to the
      Journal of Breath Research and this issue includes eight articles which describe
      the different applications of breath analysis.   We thank all the authors for
      their valuable contribution and we trust that this collection will provide useful
      information and an update to this rapidly evolving field, giving an example of
      integration among scientists who address the same topic-breath analysis-from
      different and complementary perspectives, from basic to clinical research.

PMID- 22622268
TI  - Structural isomerism in tris-tolyl halo-phosphonium and halo-arsonium tri
      halides, [(CH3C6H4)3EX][X3], (E = P, As; X = Br, I).
AB  - The group 15 ligands (o-CH(3)C(6)H(4))(3)P, (m-CH(3)C(6)H(4))(3)P, (p
      CH(3)C(6)H(4))(3)P, Ph(3)As, (o-CH(3)C(6)H(4))(3)As and (p-CH(3)C(6)H(4))(3)As
      have been reacted with two equivalents of di-iodine or di-bromine to yield
      complexes of formula R(3)EX(4) (E = P, As; X = I, Br). These halogenated group 15
      compounds are ionic, [R(3)EX][X(3)] consisting of halo-phosphonium or halo
      arsonium cations and trihalide anions. These adducts exhibit structural isomerism
      and may exist either as simple 1:1 ion pairs, [R(3)EX][X(3)], isomer (A), which
      display a weak XX interaction between cation and anion, or as a 2:1 complex,
      which consists of a [{R(3)EX}(2)X(3)](+) cationic species made up of two
      [R(3)EX](+) cations interacting with one [X(3)](-) anion. The overall charge is
      balanced by a second [X(3)](-) anion. These 2:1 species also exhibit structural
      isomerism due to subtle differences in the connectivity of the
      [{R(3)EX}(2)X(3)](+) fragment, as the {R(3)EX}(+) units may either interact at
      the same end of the [X(3)](-) ion, to give a Y-shaped motif, isomer (B), or at
      opposite ends, giving a Z-shaped motif, isomer (C). The type of structural isomer
      formed is related to the way in which [Ar(3)EX](+) cations pack together via aryl
      embraces. Isomer (A) and (C) structures form chains of side-to-side, anti
      parallel embracing cations. In (A) and (C) structures a square-like stacking
      motif of cations is observed. In contrast, isomer (B) structures feature side-to
      side, parallel embracing cations, and do not exhibit the square motif.

PMID- 22622269
TI  - Prussian blue: a new framework of electrode materials for sodium batteries.
AB  - Prussian blue and its analogues consisting of different transition-metal ions
      (Fe, Mn, Ni, Cu, Co and Zn) have been synthesized at room temperature. Insertion
      of Na into KFe(2)(CN)(6) in a carbonate electrolyte exhibited a reversible
      capacity near 100 mA h g(-1) with no capacity fade in 30 cycles. The data
      indicate that a Na-ion battery with a Prussian blue framework as a cathode will
      be feasible.

PMID- 22622270
TI  - Inconsistency as a diagnostic tool in a society of intelligent agents.
AB  - OBJECTIVE: To use the detection of clinically relevant inconsistencies to support
      the reasoning capabilities of intelligent agents acting as physicians and tutors
      in the realm of clinical medicine. METHODS: We are developing a cognitive
      architecture, OntoAgent, that supports the creation and deployment of intelligent
      agents capable of simulating human-like abilities. The agents, which have a
      simulated mind and, if applicable, a simulated body, are intended to operate as
      members of multi-agent teams featuring both artificial and human agents. The
      agent architecture and its underlying knowledge resources and processors are
      being developed in a sufficiently generic way to support a variety of
      applications. RESULTS: We show how several types of inconsistency can be detected
      and leveraged by intelligent agents in the setting of clinical medicine. The
      types of inconsistencies discussed include: test results not supporting the
      doctor's hypothesis; the results of a treatment trial not supporting a clinical
      diagnosis; and information reported by the patient not being consistent with
      observations. We show the opportunities afforded by detecting each inconsistency,
      such as rethinking a hypothesis, reevaluating evidence, and motivating or
      teaching a patient. CONCLUSIONS: Inconsistency is not always the absence of the
      goal of consistency; rather, it can be a valuable trigger for further exploration
      in the realm of clinical medicine. The OntoAgent cognitive architecture, along
      with its extensive suite of knowledge resources an processors, is sufficient to
      support sophisticated agent functioning such as detecting clinically relevant
      inconsistencies and using them to benefit patient-centered medical training and
      practice.

PMID- 22622271
TI  - [EMDR in Psychiatry. Introduction to the Supplement].
AB  - The Author, after having summarized what EMDR is, remebers the international
      aknowledgements it has received and points out the main hypothesis of functioning
      and the studies of neurophysiology. He specifies how EMDR, from an initial step
      of therapeutic technique and clinical method, has become a global approach useful
      from many fields of the psychopathology, till to the most complex post-traumatic
      situations.

PMID- 22622272
TI  - [EMDR and adaptive information processing. Psychotherapy as a stimulation  of the
      self-reparative psychological processes].
AB  - Based on the concept of traumatic event, the model of the adaptive information
      processing is described to illustrate how EMDR is applied to reprocess the trauma
      and resolve post-traumatic psychopathology. The eight phases of the EMDR
      treatment are presented together with the way an EMDR session is conducted and
      the contribution and innovation that EMDR represents in the field of therapy of
      post-traumatic states and its applicability in other symptomatic conditions.<
      span class="text23">

PMID- 22622273
TI  - [Evaluation study of clinical and neurobiological efficacy of EMDR in patients
      suffering from post-traumatic stress disorder].
AB  - Strong evidences support use of EMDR in patients suffering from post-traumatic
      stress disorder (PTSD). AIM: To evaluate clinical and neurobiological-structural
      efficacy of EMDR on drug-naive PTSD without comorbidity. MATERIALS AND METHODS:
      We made clinical evaluation and hippocampal volume measurement by MRI on 29
      subjects suffering from PTSD and on 30 healthy control-subjects. Then, patients
      were treated with EMDR and after three months of psychotherapy the clinical
      evaluation and the MRI exam were replied. RESULTS AND DISCUSSION: Our results
      demonstrated that the diagnosis of PTSD was no more possible on all the patients
      who terminated the psychotherapy (n=18). At the same time, all the patients
      showed an average increase of 6% in hippocampal volumes. CONCLUSIONS: Our
      reaserach suggests that EMDR treatment correlates not only with a significant
      improvement of symptoms of PTSD, but also with a significant increase of
      hippocampal volumes.

PMID- 22622274
TI  - [Neurobiological correlates of EMDR therapy].
AB  - The EEGs in a group of ten subjects with major psychological trauma treated with
      EMDR and in ten controls have been registered both during the listening of the
      autobiographical narrative of the index trauma (script) and during a whole EMDR
      session. The EEGs have been performed again during the last EMDR session when
      patients were free of symptoms. During script listening a prevalent activation of
      the limbic regions corresponding to prefrontal and orbitofrontal cortex has been
      registered, being explained as the emotional arousal during trauma reliving at
      the symptomatic phase. The significant decrease of such activations during the
      late asymptomatic phase represents the neurobiological correlate of recovery.
      Moreover, the evidence of significant cortical activation in the parietal-temporo
      occipital areas, during the last session, suggests a switch of the dominant
      electrical signal towards cortical areas with a prevalent cognitive function.

PMID- 22622275
TI  - [EMDR and Cognitive-Behavioural Therapy in the treatment  of Panic Disorder: a
      comparison].
AB  - AIM: A comparison between two treatments used in the Panic Disorder: EMDR, an
      evidence-based method for PTSD, and Cognitive Behavioural Therapy (CBT), which is
      nowadays considered the most effective psychotherapeutic approach for this
      disorder. METHOD: In order to evaluate any improvement obtained from the adopted
      treatment, a descriptive analysis through the use of the SPSS software has been
      carried out, on a sample of 20 subjects, divided in two groups (EMDR and CBT).
      RESULTS: From the data obtained, a tendency to improve is already clear from the
      first evaluation (after 12 sessions), in all the proposed tests. The symptomatic
      progress turned out to be quite similar in the two compared groups. EMDR
      treatment however seems to have a faster progress in symptom reduction which is
      maintained over time, as evidenced at follow-up. CONCLUSION: From the showed
      results, it is possible to confirm that both treatments are effective for the
      resolution of a Panic Disorder, even if some differences between the two
      therapies are clear, both from a symptomatic and a timing point of view. So, it
      is suggested to carry on the research in this area of interest.

PMID- 22622276
TI  - [Borderline Personality Disorder, trauma and EMDR].
AB  - The authors step by the diagnostic criteria for Borderline Personality Disorder,
      viewing them from the perspective of the Adaptive Information Processing e
      pointing them as a guide for exploration and search of traumatic interpersonal
      events connected to attachment story and which can be addressed by the
      therapeutic work with EMDR.

PMID- 22622277
TI  - Trauma, psychosis, post-traumatic stress disorder and the application of EMDR.
AB  - In this article we describe three interactions between trauma, post-traumatic
      stress disorder (PTSD) and psychosis: 1. many patients with psychotic disorders
      suffered from traumatic life experiences that play an important role in the onset
      and content of their psychosis; 2. the experience of psychosis as well as its
      psychiatric treatment may result in post-traumatic stress symptoms; 3. if
      psychosis and PTSD occur simultaneously, there is a substantial risk for
      reciprocal negative reinforcement of both symptom groups as well as for
      potentially on going traumatization. Although these interactions are highly
      relevant from a clinical perspective, they usually remain unattended in routine
      care. The three interactions will be illustrated by a case history as well as an
      impression of the psychological treatment including EMDR. We recommend to pay
      attention to traumatization and comorbid PTSD in routine care for people with
      psychosis, as well as to offer them treatment.

PMID- 22622278
TI  - [EMDR and psychopharmacological therapy in the treatment  of the post-traumatic
      stress disorder].
AB  - AIM: This study evaluates the efficacy of two different treatment for post
      traumatic stress disorder (PTSD): the psychopharmacological therapy, with a SSRI
      drug, and EMDR. METHOD: Two indipendent groups have been administered two
      different treatments: the treatment with sertraline to the group for
      psychopharmacological therapy; the treatment with one-week sessions of EMDR to
      the other group. For the evaluation of the symptoms of PTSD has been used the
      Clinician-Administered PTSD Scale (CAPS). The inclusion of the subjects in the
      two groups has been absolutely random. RESULTS: The results confirm previous
      studies available in literature, pointing out the efficacy of EMDR and of
      sertraline in improving the post-traumatic symptomatology and the levels of
      subjective sufference. But the number of subjects which at the end of the study
      didn't satisfy any more the criteria for PTSD has been absolutely greater in the
      group treated with EMDR. CONCLUSIONS: The study confirms the hypothesis of EMDR
      as a more efficacious treatment for PTSD compared to psychopharmacological
      therapy. This result could be a stimolous for further research with greater
      groups to investigate also the long term efficacy.

PMID- 22622279
TI  - Age-related percutaneous penetration part 1: skin factors.
AB  - Changes in the skin that occur in the elderly may put them at increased risk for
      altered percutaneous penetration from pharmacotherapy along with potential
      adverse effects. Skin factors that may have a role in age-related percutaneous
      penetration include blood flow, pH, skin thickness, hair and pore density, and
      the content and structure of proteins, glycosaminoglycans (GAGs), water, and
      lipids. Each factor is examined as a function of increasing age along with its
      potential impact on percutaneous penetration. Additionally, topical drugs that
      successfully overcome the barrier function of the skin can still fall victim to
      cutaneous metabolism, thereby producing metabolites that may have increased or
      decreased activity. This overview discusses the current data and highlights the
      importance of further studies to evaluate the impact of skin factors in age
      related percutaneous penetration.

PMID- 22622280
TI  - Excimer laser therapy for hairline psoriasis: a useful addition to the scalp
      psoriasis treatment algorithm.
AB  - Psoriasis is a chronic, inflammatory skin condition with negative impacts both
      physical and psychological. Scalp psoriasis, especially around the hairline, can
      cause significant impairment in quality of life due to its visibility. Options
      for treatment of facial psoriasis, including hairline involvement, are the use of
      low potency topical steroids, calcineurin inhibitors, and vitamin D analogues.
      Though the use of excimer laser for scalp psoriasis has been reported, there are
      no cases or studies specifically examining excimer laser phototherapy for the
      treatment of hairline psoriasis. We present a case of rapid improvement of
      hairline psoriasis using a regimen of 308 nm excimer laser with clobetasol spray
      and recommend an algorithm for the optimal treatment of scalp psoriasis utilizing
      currently available antipsoriatic therapies.

PMID- 22622281
TI  - [Management of obesity in childhood and adolescence: from diet to surgery].

PMID- 22622282
TI  - 24-h ambulatory recording of aortic pulse wave velocity and central systolic
      augmentation: a feasibility study.
AB  - We assessed the feasibility of ambulatory pulse wave analysis by comparing this
      approach with an established tonometric technique. We investigated 35 volunteers
      (45.6 years; 51.0% women) exclusively at rest (R study) and 83 volunteers (49.9
      years; 61.4% women) at rest and during daytime (1000-2000 h) ambulatory
      monitoring (R+A study). We recorded central systolic (cSP), diastolic (cDP) and
      pulse (cPP) pressures, augmentation index (cAI) and pulse wave velocity (PWV) by
      brachial oscillometry (Mobil-O-Graph 24h PWA Monitor) and radial tonometry
      (SphygmoCor). We applied the Bland and Altman's statistics. In the R study,
      tonometric and oscillometric estimates of cSP (105.6 vs. 106.9 mm Hg), cDP (74.6
      vs. 74.7 mm Hg), cPP (31.0 vs. 32.1 mm Hg), cAI (21.1 vs. 20.6%) and PWV (7.3 vs.
      7.0 m s(-1)) were similar (P?0.11). In the R+A study, tonometric vs.
      oscillometric assessment yielded similar values for cSP (115.4 vs. 113.9 mm Hg;
      P=0.19) and cAI (26.5 vs. 25.3%; P=0.54), but lower cDP (77.8 vs. 81.9 mm Hg;
      P<0.0001), so that cPP was higher (37.6 vs. 32.1 mm Hg; P<0.0001). PWV (7.9 vs.
      7.4 m s(-1)) was higher (P=0.0002) on tonometric assessment. The differences
      between tonometric and oscillometric estimates increased (P?0.004) with cSP
      (r=0.37), cAI (r=0.39) and PWV (r=0.39), but not (P?0.17) with cDP (r=0.15) or
      cPP (r=0.13). Irrespective of measurement conditions, brachial oscillometry
      compared with an established tonometric method provided similar estimates for cSP
      and systolic augmentation, but slightly underestimated PWV. Pending further
      validation, ambulatory assessment of central hemodynamic variables is feasible.

PMID- 22622283
TI  - TPI-287, a new taxane family member, reduces the brain metastatic colonization of
      breast cancer cells.
AB  - Brain metastases of breast and other cancers remain resistant to chemotherapeutic
      regimens that are effective systemically, in part due to the blood-brain barrier.
      We report that TPI-287, a new microtubule-stabilizing agent, displays in vitro
      cytotoxic activity similar to taxanes and epothilones. Unlike the taxanes, TPI
      287 is permeable through the blood-brain barrier. Brain-to-plasma ratios of TPI
      287 after a single injection typically exceeded one and were as high as 63.8 in
      the rat and 14.1 in the mouse. A brain-tropic derivative of the MDA-MB-231 triple
      negative breast cancer cell line, 231-BR, was used to test whether TPI-287 may be
      efficacious at preventing or treating brain metastases. TPI-287 had growth
      inhibitory effects comparable with paclitaxel when 231-BR tumor cells were
      injected into the mammary fat pad. Brain metastatic colonization was determined
      by intracardiac injection of 231-BR cells, with treatment beginning on day 3 to 4
      postinjection, culminating in a histologic count of brain metastases in brains
      necropsied days 25 to 28 postinjection. In this assay, paclitaxel, ixabepilone,
      and nab paclitaxel did not have significant inhibitory activity. TPI-287 was
      ineffective in the same assay using a 6 mg/kg every week schedule; however an 18
      mg/kg dose delivered on days 3, 7, and 11 significantly reduced the outgrowth of
      brain metastases (55% reduction, P = 0.028) and reduced proliferation in brain
      metastases (16% reduction, P = 0.008). When TPI-287 treatment was delayed until
      days 18, 22, and 26 postinjection, efficacy was reduced (17% reduction, not
      significant). These data suggest that TPI-287 may have efficacy when administered
      early in the course of the disease.

PMID- 22622284
TI  - Molecular mechanisms involved in the synergistic interaction of the EZH2
      inhibitor 3-deazaneplanocin A with gemcitabine in pancreatic cancer cells.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is characterized by overexpression of
      enhancer of Zeste homolog-2 (EZH2), which plays a pivotal role in cancer stem
      cell (CSC) self-renewal through methylation of histone H3 lysine-27 (H3K27me3).
      Against this background, EZH2 was identified as an attractive target, and we
      investigated the interaction of the EZH2 inhibitor DZNeP with gemcitabine. EZH2
      expression was detected by quantitative PCR in 15 PDAC cells, including seven
      primary cell cultures, showing that expression values correlated with their
      originator tumors (Spearman R(2) = 0.89, P = 0.01). EZH2 expression in cancer
      cells was significantly higher than in normal ductal pancreatic cells and
      fibroblasts. The 3-deazaneplanocin A (DZNeP; 5 MUmol/L, 72-hour exposure)
      modulated EZH2 and H3K27me3 protein expression and synergistically enhanced the
      antiproliferative activity of gemcitabine, with combination index values of 0.2
      (PANC-1), 0.3 (MIA-PaCa-2), and 0.7 (LPC006). The drug combination reduced the
      percentages of cells in G(2)-M phase (e.g., from 27% to 19% in PANC-1, P < 0.05)
      and significantly increased apoptosis compared with gemcitabine alone. Moreover,
      DZNeP enhanced the mRNA and protein expression of the nucleoside transporters
      hENT1/hCNT1, possibly because of the significant reduction of deoxynucleotide
      content (e.g., 25% reduction of deoxycytidine nucleotides in PANC-1), as detected
      by liquid chromatography/tandem mass spectrometry. DZNeP decreased cell
      migration, which was additionally reduced by DZNeP/gemcitabine combination (-20%
      in LPC006, after 8-hour exposure, P < 0.05) and associated with increased E
      cadherin mRNA and protein expression. Furthermore, DZNeP and DZNeP/gemcitabine
      combination significantly reduced the volume of PDAC spheroids growing in CSC
      selective medium and decreased the proportion of CD133+ cells. All these
      molecular mechanisms underlying the synergism of DZNeP/gemcitabine combination
      support further studies on this novel therapeutic approach for treatment of
      PDACs.

PMID- 22622286
TI  - In vivo muscle electroporation threshold determination: realistic numerical
      models and in vivo experiments.
AB  - In vivo electroporation is used as an effective technique for delivery of
      therapeutic agents such as chemotherapeutic drugs or DNA into target tissue cells
      for different biomedical purposes. In order to successfully electroporate a
      target tissue, it is essential to know the local electric field distribution
      produced by an application of electroporation voltage pulses. In this study three
      dimensional finite element models were built in order to analyze local electric
      field distribution and corresponding tissue conductivity changes in rat muscle
      electroporated either transcutaneously or directly (i.e., two-plate electrodes
      were placed either on the skin or directly on the skeletal muscle after removing
      the skin). Numerical calculations of electroporation thresholds and conductivity
      changes in skin and muscle were validated with in vivo measurements. Our model of
      muscle with skin also confirms the in vivo findings of previous studies that
      electroporation "breaks" the skin barrier when the applied voltage is above 50 V.

PMID- 22622285
TI  - Tryptophan scanning mutagenesis reveals distortions in the helical structure of
      the deltaM4 transmembrane domain of the Torpedo californica nicotinic
      acetylcholine receptor.
AB  - The lipid-protein interface is an important domain of the nicotinic acetylcholine
      receptor (nAChR) that has recently garnered increased relevance. Several studies
      have made significant advances toward determining the structure and dynamics of
      the lipid-exposed domains of the nAChR. However, there is still a need to gain
      insight into the mechanism by which lipid-protein interactions regulate the
      function and conformational transitions of the nAChR. In this study, we extended
      the tryptophan scanning mutagenesis (TrpScanM) approach to dissect secondary
      structure and monitor the conformational changes experienced by the deltaM4
      transmembrane domain (TMD) of the Torpedo californica nAChR, and to identify
      which positions on this domain are potentially linked to the regulation of ion
      channel kinetics. The difference in oscillation patterns between the closed- and
      open-channel states suggests a substantial conformational change along this
      domain as a consequence of channel activation. Furthermore, TrpScanM revealed
      distortions along the helical structure of this TMD that are not present on
      current models of the nAChR. Our results show that a Thr-Pro motif at positions
      462-463 markedly bends the helical structure of the TMD, consistent with the
      recent crystallographic structure of the GluCl Cys-loop receptor which reveals a
      highly bent TMD4 in each subunit. This Thr-Pro motif acts as a molecular hinge
      that delineates two gating blocks in the deltaM4 TMD. These results suggest a
      model in which a hinge-bending motion that tilts the helical structure is
      combined with a spring-like motion during transition between the closed- and open
      channel states of the deltaM4 TMD.

PMID- 22622288
TI  - Microfluidic micropipette aspiration for measuring the deformability of single
      cells.
AB  - We present a microfluidic technique for measuring the deformability of single
      cells using the pressure required to deform such cells through micrometre-scale
      tapered constrictions. Our technique is equivalent to whole-cell micropipette
      aspiration, but involves considerably simpler operation, less specialized
      equipment, and less technical skill. Single cells are infused into a microfluidic
      channel, and then deformed through a series of funnel-shaped constrictions. The
      constriction openings are sized to create a temporary seal with each cell as it
      passes through the constriction, replicating the interaction with the orifice of
      a micropipette. Precisely controlled deformation pressures are generated using an
      external source and then attenuated 100 : 1 using an on-chip microfluidic
      circuit. Our apparatus is capable of generating precisely controlled pressures as
      small as 0.3 Pa in a closed microchannel network, which is impervious to
      evaporative losses that normally limit the precision of such equipment. Intrinsic
      cell deformability, expressed as cortical tension, is determined from the
      threshold deformation pressure using the liquid-drop model. We measured the
      deformability of several types of nucleated cells and determined the optimal
      range of constriction openings. The cortical tension of passive human neutrophils
      was measured to be 37.0 +/- 4.8 pN MUm(-1), which is consistent with previous
      micropipette aspiration studies. The cortical tensions of human lymphocytes, RT4
      human bladder cancer cells, and L1210 mouse lymphoma cells were measured to be
      74.7 +/- 9.8, 185.4 +/- 25.3, and 235.4 +/- 31.0 pN MUm(-1) respectively. The
      precision and usability of our technique demonstrates its potential as a
      biomechanical assay for wide-spread use in biological and clinical laboratories.

PMID- 22622287
TI  - Effect of mixed-phospholipid layer on phospholipase D reaction-induced vesicle
      rupture.
AB  - Spherical phospholipid bilayers, or vesicles, were prepared layer by layer using
      a double-emulsion technique, which allows the outer layer of the vesicles to be
      formed with two phospholipids that have different head groups:
      phosphatidylcholine (PC) and phosphatidylethanolamine. At the outer layer of the
      vesicles, the phospholipase D (PLD) catalyzed for the conversion of PC to
      phosphatidic acid. The reaction caused by PLD induced the curvature change of the
      vesicles, which eventually led to the rupture of the vesicles. Before the
      investigation, the ratio of dioleoylphosphatidylethanolamine to
      oleoylhydroxyphosphatidylethanolamine was found as a condition such that the
      vesicles made with the mixed lipids were as stable as those made with pure
      dioleoylphosphatidylcholine. Response time from the PLD injection to vesicle
      rupture was monitored by the composition of the outer layer by the fluorescence
      intensity change of pH-sensitive dye encapsulated in the vesicles. The response
      time began to be slowed at approximately 30 % PC. The response times for the
      compositions were associated with the surface density of PC at the outer layer.
      These results also seem to be determined by the size of PLD, specifically the PLD
      active site.

PMID- 22622289
TI  - What is it like?

PMID- 22622290
TI  - The Telltale Heart or the importance of the "Tap Test" in electroconvulsive
      therapy (ECT).
AB  - The "Tap Test" is a maneuver used to test the functioning of the
      electroencephalogram and electromyogram leads just prior to electroconvulsive
      therapy. Here we present a brief case and image that reinforces the importance of
      this simple test.

PMID- 22622291
TI  - Effects of propofol and ketamine as combined anesthesia for electroconvulsive
      therapy in patients with depressive disorder.
AB  - BACKGROUND: Electroconvulsive therapy (ECT) is a preferred therapy for major
      depressive disorder. Intravenous propofol, a sedative and hypnotic agent, is one
      of the choices of anesthetic for ECT. Ketamine, another anesthetic agent,
      providing sedation, amnesia, and analgesia, can also be used in patients
      undergoing ECT owing to its rapid action and persistent antidepressive effect.
      One adverse effect of ketamine is cardiovascular excitement, which may be reduced
      by propofol. Currently, the effects of combined anesthesia (propofol and
      ketamine) for patients with depressive disorder who have undergone ECT are
      unclear. The purpose of this study was to investigate the effects of the combined
      agents for patients undergoing ECT. METHODS: Forty-eight patients with Hamilton
      Depression Rating Scale (HDRS) scores greater than 20 were randomly divided into
      3 groups (n=16 each): propofol group (group P), ketamine group (group K), and
      propofol plus ketamine group (group PK). Propofol (1.5 mg/kg), ketamine (0.8
      mg/kg), and propofol (1.5 mg/kg) plus ketamine (0.8 mg/kg) were infused to each
      group of patients, respectively, before ECT by an anesthesiologist with no
      knowledge of the HDRS score. For the purpose of this study, the patients received
      a single ECT treatment and were assessed for depression using the HDRS scores (1
      day before ECT and days 1, 2, 3, and 7 after the ECT treatment) by a psychiatrist
      with no knowledge of the randomization group. After the final assessment, the
      patients received further treatment as needed up to 3 treatments per week.
      Seizure energy index, seizure duration, and adverse effects were observed during
      anesthesia by a nurse with no knowledge of the study group. RESULTS: The HDRS
      scores improved earlier in group K and group PK. Decreases in HDRS scores were
      significantly greater in group K and group PK compared with those in group P. The
      adverse effects in group PK were fewer than those in group K. Seizure energy
      index and seizure duration in group K and group PK were higher and longer than
      those in group P during ECT. CONCLUSION: The results suggested that propofol
      combined with ketamine anesthesia might be the first-choice anesthesia in
      patients with depressive disorder undergoing ECT.

PMID- 22622292
TI  - Electrical parameters and the efficacy of ECT: pulse frequency or stimulus train
      duration?

PMID- 22622294
TI  - Maintenance electroconvulsive therapy in a patient with multiple system atrophy
      and bipolar disorder.
AB  - Multiple system atrophy is a rapidly progressive neurodegenerative disorder with
      no known cure. It is a clinical diagnosis with no confirmation available other
      than brain biopsy after death. We report the successful treatment of multiple
      system atrophy co-occurring with bipolar disorder in a 62-year-old man using
      electroconvulsive therapy.

PMID- 22622295
TI  - Novel approach to managing severely labile blood pressure during maintenance
      electroconvulsive therapy in a man with psychotic depression and Parkinson
      disease.
AB  - Electroconvulsive therapy cannot proceed safely unless blood pressure is within
      the reference range. Finding the cause of very high or low blood pressure can be
      very difficult, time consuming, and expensive. We suggest a more valid and
      reliable time to check blood pressure. This is highlighted in the case of a man
      that became riddled with iatrogenic complications and needless treatments.

PMID- 22622296
TI  - Readmission to psychiatric hospital after treatment for depression with
      electroconvulsive therapy: the effect of planned readmissions.
AB  - OBJECTIVES: To assess the effect of planned readmissions on readmission risk for
      electroconvulsive therapy (ECT)-treated patients. METHODS: A naturalistic
      historical study compared the readmission risk for depressed ECT-treated patients
      to depressed patients not treated with ECT while accounting for planned
      readmissions. RESULTS: Initial analyses revealed that ECT-treated patients were
      at greater risk of readmission compared to patients not treated with ECT.
      However, after accounting for planned readmissions, these differences became
      nonsignificant. LIMITATIONS: Only readmissions to a single psychiatric hospital
      were examined. Therefore, these data may underestimate readmission rates.
      CONCLUSIONS: Not accounting for planned readmissions may lead to overestimations
      of negative outcome.

PMID- 22622297
TI  - Multiple episodes of intraictal cessation during electroconvulsive therapy.
AB  - A recent case reported an episode of a "stop-start-stop" phenomenon during an
      electroconvulsive therapy treatment. We report an example of multiple stop-start
      stop episodes during several electroconvulsive therapy treatments of a 16-year
      old boy.

PMID- 22622298
TI  - Treatment of post-electroconvulsive therapy headache with topical methyl
      salicylate.
AB  - Headache after administration of electroconvulsive therapy (ECT) is common,
      affecting approximately half of patients treated. Post-ECT headache is typically
      treated with acetaminophen or nonsteroidal anti-inflammatory drugs but
      occasionally requires agents such as sumatriptan, opioids, or beta-blockers. We
      report on a patient whose severe post-ECT headaches responded completely to
      methyl salicylate ointment, applied to the area of his temporalis and masseter
      muscles. Topical methyl salicylate is generally well tolerated and may be a
      viable option for some patients with post-ECT headache.

PMID- 22622299
TI  - Electroconvulsive therapy in the presence of atrial septal defect: a case report.
AB  - There is limited literature on the use of electroconvulsive therapy in patient
      with congenital heart defect. We present a case of a 24-year-old woman with
      diagnosis of persistent delusion disorder with depression and congenital heart
      defect of ostium secundum type treated successfully with a course of
      electroconvulsive therapies.

PMID- 22622300
TI  - Rocuronium and sugammadex used effectively for electroconvulsive therapy in a
      patient with Brugada syndrome.
AB  - We report the successful anesthetic management of a patient with Brugada syndrome
      who underwent electroconvulsive therapy to treat bipolar disorder. Suxamethonium
      and neostigmine were contraindicated to avoid the vagotonic effects that can
      precipitate ventricular fibrillation during anesthesia in patients with Brugada
      syndrome. The combination of 1.2 mg/kg rocuronium and 10 mg/kg sugammadex was
      effectively and safely used to induce and antagonize neuromuscular block for 8
      consecutive electroconvulsive therapy sessions in this patient.

PMID- 22622302
TI  - Electroconvulsive therapy (ECT) after pulmonary edema.
AB  - We report a case of pulmonary edema after electroconvulsive therapy (ECT) in an
      88-year-old man with controlled hypertension and treatment-refractory depression.
      Despite this unexpected episode of pulmonary edema, the patient was able to
      complete this course of ECT without further complications. Because the pulmonary
      edema was thought to be due to extremely elevated blood pressures, nitroglycerine
      and esmolol were used during subsequent treatments, and electrode placement was
      changed to bilateral to speed recovery.

PMID- 22622301
TI  - Effects on intracranial pressure of electroconvulsive therapy.
AB  - Electroconvulsive therapy (ECT) is thought to raise intracranial pressure (ICP)
      after an increase of blood pressure. In depressed patients (n=17) treated with
      ECT, using transcranial Doppler, pulsatility index (PI; as indicator of ICP) and
      blood pressures were prospectively measured. The highest PI was measured just
      after anesthesia induction and muscle relaxation. Blood pressures increased
      significantly after succinylcholine and thereafter but did not correlate to PI.
      After anesthesia and muscle relaxation, the PI was higher than just before ECT;
      the PI was lower during seizure activity and after ECT. Therefore, ECT itself
      seemed not to raise ICP.

PMID- 22622303
TI  - Electroconvulsive therapy for a patient with metallic internal fixation in
      mandible.
AB  - Electroconvulsive therapy (ECT) in the presence of metal in the skull may cause
      concern among clinicians. The literature is sparse, with only a few case reports
      in this area. We present here a case where ECT was administered in a patient with
      metallic internal fixation for the fracture of mandible. The 37-year-old man
      presented with severe depression, suicide risk, and alcohol dependence.
      Administration of ECT was uneventful, with no complications during ECT or at
      follow-up; and there was successful resolution of symptoms. This case report
      demonstrates that ECT may be safe in the presence of metallic implants in
      mandible.

PMID- 22622304
TI  - Use of electroconvulsive therapy in a patient with chorea neuroacanthocytosis and
      prominent delusions.
AB  - A middle-aged white man with a diagnosis of chorea neuroacanthocytosis developed
      progressive and distressing persecutory delusions with an obsessional component.
      Pharmacotherapy was ineffective in controlling the symptoms or halting their
      progression. Electroconvulsive therapy was attempted with very limited success
      but had to be discontinued owing to mild elation and increased irritability. The
      patient's distress was only improved after his transfer to a nursing home
      specializing in Huntington disease.

PMID- 22622305
TI  - Electroconvulsive therapy in Slovakia.
AB  - The aim of the study was to review and describe contemporary practice of
      electroconvulsive therapy (ECT) in Slovakia. A 30-item containing questionnaire
      was sent to all inpatient psychiatric institutions in Slovakia. Electroconvulsive
      therapy was offered in 33 of 36 psychiatric departments and ECT wards that
      responded. All the psychiatric services except 1 replied to the questionnaire
      (n=32; 97%). Sixteen departments (50%) used a sine wave device. Bitemporal or
      bifrontotemporal electrode placement is evidently preferred option in 93.8% of
      all departments. The main diagnostic indication for ECT in Slovakia is
      depression. Both national guidelines and continuing education are missing.

PMID- 22622306
TI  - Management of severe postictal agitation after electroconvulsive therapy with
      bispectrum electroencephalogram index monitoring: a case report.
AB  - Postictal agitation (PIA) with possible severe implications occurs in
      approximately 10% of electroconvulsive therapy (ECT) sessions. The pathomechanism
      is not well understood, and suggested treatments are empirical based. We report a
      case of repetitive (47/57 sessions [83%]) severe PIA after ECT in a case with
      severe depression. If the minimal bispectrum EEG index (BIS) value, meaning the
      deepest level of sedation of the thiopental narcosis dropped below 50, PIA
      occurred in only 9.1%. Bispectral index (BIS) monitoring made prediction and
      prevention of PIA possible to some degree. Postictal agitation might occur in
      vulnerable patients when initial depth of anesthesia is too light.

PMID- 22622309
TI  - Cyclometalated platinum(II) diimine complexes: synthetically tuning the
      photophysical and electrochemical properties.
AB  - Presented is the synthesis of an array of 16 heteroleptic phosphorescent diimine
      complexes of platinum(II) with electronically diverse ligand spheres and their
      full spectroscopic, photophysical, and electrochemical characterization. The
      complexes were found to exhibit luminescence (480-500 nm) in deaerated solutions
      at room temperature from a long-lived (3)LC state (tau = 2-3 MUs) that exhibits
      significant metal character perturbed by a low-lying (1)MLCT state.
      Interestingly, emission from a (3)MLCT state was not observed as is the case with
      many other polypyridine-based d-block complexes. Electrochemical intermediates
      proved stable as multiple reversible reductions between -1 and -2 V vs. SCE were
      noted during cyclic voltammetry experiments unveiling the potential of these
      luminophores for use in a variety of optoelectronic and solar energy conversion
      applications.

PMID- 22622308
TI  - Transcriptome profiling and in silico analysis of somatic embryos in Japanese
      larch (Larix leptolepis).
AB  - Japanese larch (Larix leptolepis) is an ecologically and economically important
      species mainly grown in northeastern China, Japan and Europe. However, erratic
      flowering and poor germplasm resources caused by high embryo abortion rates have
      hampered breeding of Larix species. Somatic embryogenesis (SE) is an effective
      tool for the production of L. leptolepis with desirable characteristics, such as
      expression of totipotency, preparation of synthetic seeds, and genetic
      transformation. However, public genomic resources for this species are limited.
      We sequenced 591,759 raw expressed sequence tags (ESTs) from a 454 sequencing
      cDNA library of L. leptolepis somatic embryos, resulting in 572,403 high-quality
      reads. These reads were assembled into 70,927 unique sequences (UniGenes),
      including 32,321 contigs and 38,606 singletons. After removal of low-quality
      sequences, 65,115 UniGenes were annotated using the UniProtKB program. Based on
      their sequence similarity with known proteins, the matched 30,372 sequences from
      664 species were estimated to represent approximately 19,000 unique genes. Gene
      ontology analysis revealed 21,324 UniGenes assigned to 51 categories. By Kyoto
      Encyclopedia of Genes and Genomes mapping, 25,773 transcripts were associated
      with 160 biochemical pathways. Further analysis screened four signal transduction
      pathways represented by 337 enzymes and 17 secondary metabolites. In silico
      analysis reveals that 207 UniESTs in Larix are homologous to MAPKs genes
      identified from other model plants, which may be involved in regulating SE
      development. This study provides an initial insight into the Larix transcriptomes
      of the pro-embryogenic mass and is a sound basis for future studies. KEY MESSAGE:
      We constructed a large, full-length 454 sequencing cDNA library of Larix
      leptolepis during somatic embryogenesis. More than 590,000 sequences were
      obtained and a deep-coverage EST database was constructed.

PMID- 22622310
TI  - [Clinicopathological features, prognosis and influence in the adjuvant treatment
      of the risk recurrence groups determined by the 21 gene expression profile,
      Oncotype Dx(r), in early breast cancer].
AB  - BACKGROUND: Adjuvant chemotherapy (ACT) reduces recurrence and mortality in
      breast cancer (BC); however, not all patients require ACT. Oncotype Dx(r) (ODX)
      explores the expression of 21 genes and the risk of recurrence BC. OBJECTIVES: To
      determine the clinicopathologic characteristics, prognosis, and the prescription
      for ACT in early BC according to ODX risk groups. METHODS: 36 patients with
      resected stage I-IIA BC, axillary lymph node-negative or 1-3+, hormonal receptor
      (HR)-positive, HER2 negative. Three groups were designed by ODX: low (LG), medium
      (MG) and high-risk groups (HG). RESULTS: LG 23 patients (63.9%), MG eight (22.2%)
      and HG five (13.9%). We detected high expression of Ki-67 in MG and HG in
      relation to LG, 21.1 and 32.5 versus 10.1%, respectively (p = 0.007) and lower ER
      positive, 85.3, 85.4 and 56.9%, respectively (p = 0.005). Recurrence score: LG 12
      (0-18), MG 23 (19-27) and HG 47 (36-57); p < 0.000. Pre-ODX, we planned ACT in
      21/36 patients (58.3%) and post-ODX only 9/36 patients (25%) received it. No
      recurrences or deaths were observed in all groups. CONCLUSIONS: In early BC, 64%
      have low recurrence risk. High-risk cases presented elevated Ki-67 and lower ER
      expression. ODX modifies the therapeutic recommendation in 57.2% of cases.

PMID- 22622311
TI  - [Renal sympathetic denervation (RSD): a new, non-pharmacologic therapeutic
      strategy for treatment-resistant hypertension (TRH). Report of the first
      procedure in Mexico].
AB  - A patient with resistant hypertension successfully treated with sympathetic renal
      denervation (SRD) is reported. This novel therapy is based on the partial
      ablation of the renal nerves by applying radiofrequency to the luminal surface of
      the renal arteries using vascular catheterization techniques. This first case
      performed in Mexico has two particular features: (i) an electrophysiology
      ablation catheter was employed due to the unavailability of the system
      specifically designed for SDR, and (ii) under current denervation protocols, the
      anatomical complexity of the targeted renal arteries would have excluded our
      patient from this procedure and thus deprived her of the benefit provided.

PMID- 22622312
TI  - [Hydrocephaly does not modify neuroblast chain migration in the subventricular
      zone (SVZ)].
AB  - BACKGROUND: Genetic mutations that affect cilia beating have shown that ependymal
      cilia not only contribute to the movement of cerebrospinal fluid, but also to
      direct migratory neuroblasts in the subventricular zone. These ciliary
      disturbances are associated with hydrocephalus. OBJECTIVE: To determine whether
      hydrocephalus per se alters migration and proliferation of neuroblasts in the
      subventricular zone, the largest niche of neural stem cells in the adult brain.
      METHODS: A vinyl acetate film was surgically inserted into the atrium of the
      Aqueduct of Sylvius of P60 Balb/C mice. Seven days later, we analyzed the
      ventricular dilatation, the number of proliferative neural progenitors and
      migratory neuroblasts, and the organization of neuroblast chains. RESULTS: This
      model of obstructive hydrocephalus increased the size of the lateral ventricles.
      No statistically significant differences in cell proliferation (controls 13 +/-
      2.2 vs. the hydrocephalic group 11 +/- 2.9 cells per field) or in the number of
      neuroblasts (controls 32 +/- 3.6 vs. the hydrocephalic group 27 +/- 4.8 cells per
      field). No differences were observed in the migration pattern of neuroblasts.
      CONCLUSION: Sub-chronic hydrocephalus did not modify the proliferation of neural
      precursors or the migration pattern of neuroblasts in the subventricular zone.
      This suggests that only the CSF flow and the dissolved signaling proteins are the
      main regulators of the neuronal migration in vivo.

PMID- 22622313
TI  - [Prevalence of metabolic syndrome (MS) in patients with type 1 diabetes (DM1)].
AB  - BACKGROUND: Double diabetes is the association between type 1 diabetes mellitus
      (DM1) and metabolic syndrome (MS). The prevalence of hypertension, dyslipidemia,
      central obesity and macrovascular complications has increased in DM1 patients,
      regardless glycemic control. OBJECTIVE: To determine the prevalence of MS in
      patients with DM1. METHODS: We performed a descriptive cross-sectional study of
      clinical characteristics of DM1 patients. Biochemical and anthropometric
      parameters were determined and the presence of hypertension, dyslipidemia and
      central obesity were assessed. MS was defined according to American Heart
      Association/National Heart, Lung and Blood Institute (AHA/NHLBI) and National
      Cholesterol Education Program: Adult Treatment Panel III (NCEP:ATPIII) criteria.
      RESULTS: For this study 130 patients were evaluated (66% women) with a median age
      of 29.5 years (interquartile range [RI]: 22-36) and disease evolution of 12 years
      (RI: 7-17). 47% had dyslipidemia, 23% hypoalphalipoproteinemia, 11%
      hypertrigliceridemia and 13% both pathologies. Additionally 64% had high level of
      low-density lipoprotein cholesterol (C-LDL) and 21% had hypertension. According
      to AHA/NHLBI criteria, 37.5% (with three parameters) and 14% (more than three
      parameters) of patients were estimated to have MS. On the other hand, using
      NCEP:ATPIII criteria 25% (three parameters) and 11.5% (more than three
      parameters) had MS. Patients with DM1 and MS were older, heavier and had greater
      body mass index (BMI) and waist circumference. CONCLUSION: The presence of MS in
      patients with DM1 is evident in our study. There are no differences in
      glycosylated hemoglobin or insulin doses between groups with and without MS.

PMID- 22622314
TI  - [Prophylaxis of venous thromboembolic disease in high-risk orthopedic surgery].
AB  - Venous thromboembolism (VTE) is a worldwide public health problem, with an annual
      incidence of 1-2 cases/1,000 individuals in the general population and a 1-5%
      associated mortality. Orthopedic surgery is a major surgical risk factor for VTE,
      but the problem is more important for patients with hip and knee joint
      replacement, multiple traumatisms, severe damage to the spine, or large
      fractures. Thromboprophylaxis is defined as the strategy and actions necessary to
      diminish the risk of VTE in high-risk orthopedic surgery. Antithrombotics may
      prevent VTE. At the end of this paper, we describe a proposal of
      thromboprophylaxis actions for patients requiring high-risk orthopedic surgery,
      based on the opinion of specialists in Orthopedics and Traumatology who work with
      high-risk orthopedic surgery patients. A search for evidence about this kind of
      surgery was performed and a 100-item inquiring instrument was done in order to
      know the opinions of the participants. Then, recommendations and considerations
      were built. In conclusion, this document reviews the problem of VTE in high-risk
      orthopedic surgery patients and describes the position of the Colegio Mexicano de
      Ortopedia y Traumatologia related to VTE prevention in this setting.

PMID- 22622315
TI  - [Epidemiology, physiopathology and diagnosis of pulmonary hypertension in hepatic
      (PH) cirrhosis].
AB  - Liver cirrhosis is a complex and progressive disease associated with high
      mortality. In developing countries, alcoholic liver disease is the most common
      form of liver cirrhosis, followed by chronic viral disease, especially hepatitis
      C virus infection. Cirrhosis is associated with systemic and splanchnic
      hemodynamic abnormalities, including increased vascular volume, decreased
      systemic vascular resistance, and increased cardiac output. At the splanchnic
      vascular bed, increases in portal flow and intrahepatic resistance have been
      described, inducing portal hypertension. Pulmonary arterial hypertension is a
      progressive disease of pulmonary circulation, without left ventricle and valvular
      heart disease; it is closely related with structural changes in pulmonary
      arteries. Idiopathic pulmonary arterial hypertension is related to abnormalities
      in cellular signals, inducing arterial hypertrophy and increased vascular tone.
      Porto-pulmonary hypertension includes simultaneous portal and pulmonary arterial
      hypertension. To confirm disease, it is important to exclude concomitant heart
      disease. Porto-pulmonary hypertension requires important components: portal
      hypertension, shear vascular stress, and cellular activation with pulmonary
      arterial hypertrophy. In this short manuscript, the epidemiology, patho
      physiology, and diagnostic criteria of the disease are reviewed to optimize early
      diagnosis and treatment.

PMID- 22622316
TI  - [The skin and the endocrine system].
AB  - The skin is an organ closely related to the endocrine system. The endocrine
      system has an important role in the skin development and its normal physiology.
      Skin, pilosebaceous unit, eccrine, and apocrine sweat glands have hormonal
      receptors and are targets of hormones. On the other hand, the skin synthesizes a
      variety of hormones and thus it may be considered as an endocrine organ. This
      article is an overview of the effects of some hormones on the skin.

PMID- 22622317
TI  - [Endovascular approach in the management of intracranial aneurysms. Part 1: basic
      concepts and devices].
AB  - Neurological endovascular therapy is a discipline that has shown effectiveness
      and safety in the management of intracranial aneurysms, however recanalization
      persists as one of the most important obstacles to overcome. Precise knowledge of
      the anatomy and hemodynamics of the aneurysm and the parent artery as well as
      currently available endovascular devices, are decisive in the analysis and to
      design a specific treatment plan for each case. In this manner we ensure, as long
      as possible, success and durability of the treatment.

PMID- 22622318
TI  - [Endovascular approach in the management of intracranial aneurysms. Part 2:
      indications and therapeutic strategy].
AB  - The success and stability of the occlusion of intracranial aneurysms can be
      achieved after an adequate conceptualization and implementation of current
      endovascular techniques, which in turn should be based on knowledge of available
      devices and the analysis of the specific characteristics the aneurysm and its
      parent artery to what we called aneurysmal complex.

PMID- 22622319
TI  - [Vestibular schwannoma].
AB  - The vestibular schwannoma is a benign intracranial tumor of the myelin-forming
      cells of the vestibulocochlear nerve or cranial nerve VIII. It comprises 8-10% of
      all intracranial neoplasms in adults. It originates in the vestibular portion of
      the cranial nerve VIII and it is located in the cerebellopontine angle. This
      disorder is characterized by ipsilateral hearing loss, tinnitus, disturbed sense
      of balance and altered gait, facial numbness, muscle weakness or ipsilateral
      paralysis. This report presents the magnetic resonance imaging of a patient with
      this rare condition.

PMID- 22622320
TI  - [Soldiers and HIV: impact of medical knowledge on the analysis of discrimination
      in the constitution].
AB  - In 2007 the Mexican Supreme Court issued several opinions dealing with military
      personnel dismissed from the Army because of their being HIV-positive. The author
      describes the main questions under discussion and the core arguments developed by
      the Court, and stresses three reasons why these cases deserve close attention:
      positively, because they reinforced the use of the proportionality principle as a
      tool for identifying discriminatory norms and because they opened the door to the
      use of specialized scientific knowledge in constitutional adjudication;
      negatively, because they failed to build on the direct normative efficacy of the
      right to health.

PMID- 22622321
TI  - [History of systemic sclerosis].
AB  - Systemic sclerosis (Scleroderma) is a generalized disease of the connective
      tissue, whose etiology is unknown, and which produces fibrosis and degenerative
      changes in the skin (scleroderma), synovial membrane, arterial vessels, skeletal
      muscle, and certain internal organs, especially the gastrointestinal tract, lung,
      heart, and kidney. Patients with cutaneous alterations, which could have been
      scleroderma cases, have been described since the most distant ancient times, and
      since the end of XIX century its recognition has been accurate. In the past
      century more precise diagnoses and treatments were possible because of the
      knowledge of its pathogenesis and its classification into clinic-serologic
      subgroups. We intend to recall the names and contributions of the doctors who
      collaborated with the advances throughout history.

PMID- 22622322
TI  - What factors are most relevant to the assessment of work ability of employees on
      long-term sick leave? The physicians' perspective.
AB  - PURPOSE: To reach insurance physician (IPs) consensus on factors that must be
      taken into account in the assessment of the work ability of employees who are
      sick-listed for 2 years. METHODS: A Delphi study using online questionnaires was
      conducted from October 2010 to March 2011. RESULTS: One hundred and two insurance
      physicians reached a consensus on important factors for return to work (RTW) of
      employees on long-term sick leave; from those factors, the most relevant for the
      assessment of work ability was determined. From a total of 22 relevant factors
      considered for the return to work of long-term sick-listed employees, consensus
      was reached on nine relevant factors that need to be taken into account in the
      assessment of the work ability of employees on long-term sick leave. Relevant
      factors that support return to work are motivation, attitude towards RTW,
      assessment of cognitions and behaviour, vocational rehabilitation in an early
      stage and instruction for the sick-listed employee to cope with his disabilities.
      Relevant factors that hinder RTW are secondary gain from illness, negative
      perceptions of illness, inefficient coping style and incorrect advice of treating
      physicians regarding RTW. CONCLUSIONS: Non-medical personal and environmental
      factors may either hinder or promote RTW and must be considered in the assessment
      of the work ability of long-term sick-listed employees. Assessment of work
      ability should start early during the sick leave period. These factors may be
      used by IPs to improve the quality of the assessment of the work ability of
      employees on long-term sick leave.

PMID- 22622323
TI  - Measurement of pentane in expiratory gas during rabbit hepatic ischemia/
      reperfusion by solid-phase microextraction and gas chromatography-mass
      spectrometry (SPME GC/MS).
AB  - The aim of this study was to determine the changes in the pentane concentration
      of expiratory gas as well as the relationship between this pentane concentration
      and hepatic oxidative stress during rabbit hepatic ischemia/reperfusion using
      solid-phase microextraction (SPME) and gas chromatography-mass spectrometry
      (GC/MS). 45 white male rabbits with body weights between 2.5 and 3.0 kg were
      randomly assigned to the following three groups: the 10 min ischemia group (group
      S); the 20 min ischemia group (group M); or the 30 min ischemia group(group L).
      Expiratory gases were collected prior to ischemia (T0) and for 1, 10, 20, 30, 60
      and 120 min (T1-T6) following reperfusion. Pentane concentrations were determined
      using SPME and GC/MS. In addition, arterial blood samples were collected, and
      serum aminotransferase(AST) and malondialdehyde (MDA) concentrations were
      measured. In the three groups, the pentane concentrations of the expiratory gases
      at points T1 and T2 were significantly increased(P < 0.05) compared with those at
      point T0, and the serum AST and MDA concentrations at points T5 and T6 were also
      significantly increased (P < 0.05) compared with those at point T0.Therefore, the
      use of SPME in combination with GC/MS represents an improved anesthesia system
      that can be used to continuously measure the concentration of pentane in
      expiratory gases, which can reflect the degree of oxidative stress during hepatic
      ischemia/reperfusion.

PMID- 22622324
TI  - Physical self-concept and disturbed eating attitudes and behaviors in French
      athlete and non-athlete adolescent girls: direct and indirect relations.
AB  - This study aims to investigate the direct and indirect associations between
      physical self-subdomains, physical self-worth, global self-worth, and disturbed
      eating attitudes and behaviors among French non-elite athlete and non-athlete
      adolescent girls. A sample of adolescent girls including 50 ballet dancers, 41
      basketball players, and 47 non-athletes was used in this study. Data obtained
      from the ballet dancer and basketball player subsamples revealed significant,
      sample-specific as well as common, direct relations between global and physical
      self-perceptions and disturbed eating attitudes and behaviors, as well as
      significant indirect relations (via global self-worth and physical self-worth)
      between specific physical self-perceptions and disturbed eating attitudes and
      behaviors. In contrast, no association was found between global and physical self
      perceptions in the sample of non-athlete adolescent girls.

PMID- 22622325
TI  - A robust doubly interpenetrated metal-organic framework constructed from a novel
      aromatic tricarboxylate for highly selective separation of small hydrocarbons.
AB  - A microporous metal-organic framework, for the first time, has been developed for
      highly selective separation of industrially important C(1), C(2) and C(3)
      hydrocarbons at room temperature.

PMID- 22622326
TI  - Reassortants of pandemic influenza A virus H1N1/2009 and endemic porcine HxN2
      viruses emerge in swine populations in Germany.
AB  - The incursion of the human pandemic influenza A virus H1N1 (2009) (H1N1 pdm) into
      pig populations and its ongoing co-circulation with endemic swine influenza
      viruses (SIVs) has yielded distinct human-porcine reassortant virus lineages. The
      haemagglutinin (HA) gene of H1N1 pdm was detected in 41 influenza virus-positive
      samples from seven swine herds in north-west Germany in 2011. Eight of these
      samples yielded virus that carried SIV-derived neuraminidase N2 of three
      different porcine lineages in an H1N1 pdm backbone. The HA sequences of these
      viruses clustered in two distinct groups and were distinguishable from human and
      other porcine H1 pdm by a unique set of eight non-synonymous mutations. In
      contrast to the human population, where H1N1 pdm replaced seasonal H1N1, this
      virus seems to co-circulate and interact more intensely with endemic SIV
      lineages, giving rise to reassortants with as-yet-unknown biological properties
      and undetermined risks for public health.

PMID- 22622327
TI  - Extracellular matrix constituents interfere with Newcastle disease virus spread
      in solid tissue and diminish its potential oncolytic activity.
AB  - Advanced melanoma cells, characterized by resistance to chemotherapy, have been
      shown to be highly sensitive to oncolysis by Newcastle disease virus (NDV). In
      the present study, we investigated the capacity of NDV to specifically infect and
      spread into solid tissues of human melanoma and lung carcinoma, in vivo and ex
      vivo. For this purpose a new model of SCID-beige mice implanted with human
      melanoma was developed. Surprisingly, the replication competent NDV-MTH and the
      attenuated, single-cycle replication NDV-HUJ strains, demonstrated a similar
      oncolytic activity in the melanoma-implanted mice. Further, ex vivo analysis,
      using organ cultures derived from the melanoma tissues indicated a limited spread
      of the two NDV strains in the tissue. Extracellular matrix (ECM) molecules,
      notably heparin sulfate and collagen, were found to limit viral spread in the
      tissue. This observation was validated with yet another solid tumour of human
      lung carcinoma. Taken together, the results indicate that the ECM acts as a
      barrier to virus spread within solid tumour tissues and that this restriction
      must be overcome to achieve effective oncolysis with NDV.

PMID- 22622328
TI  - Hantavirus structure--molecular interactions behind the scene.
AB  - Viruses of the genus Hantavirus, carried and transmitted by rodents and
      insectivores, are the exception in the vector-borne virus family Bunyaviridae,
      since viruses of the other genera are transmitted via arthropods. The single
      stranded, negative-sense, RNA genome of hantaviruses is trisegmented into small,
      medium and large (S, M and L) segments. The segments, respectively, encode three
      structural proteins: nucleocapsid (N) protein, two glycoproteins Gn and Gc and an
      RNA-dependent RNA-polymerase. The genome segments, encapsidated by the N protein
      to form ribonucleoproteins, are enclosed inside a lipid envelope that is
      decorated by spikes composed of Gn and Gc. The virion displays round or
      pleomorphic morphology with a diameter of roughly 120-160 nm depending on the
      detection method. This review focuses on the structural components of
      hantaviruses, their interactions, the mechanisms behind virion assembly and the
      interactions that maintain virion integrity. We attempt to summarize recent
      results on the virion structure and to suggest mechanisms on how the assembly is
      driven. We also compare hantaviruses to other bunyaviruses with known structure.

PMID- 22622329
TI  - Identification of a novel NLS of herpes simplex virus type 1 (HSV-1) VP19C and
      its nuclear localization is required for efficient production of HSV-1.
AB  - Herpes simplex virus type 1 (HSV-1) triplex is a complex of three protein
      subunits, consisting of two copies of VP23 and one copy of VP19C. Here, we
      identified a non-classical NLS of VP19C between aa 50 and 61, and the nuclear
      import of VP19C was mediated by RanGTP and importin beta1-, but not importin
      alpha5-, dependent pathway. Additionally, recombinant virus harbouring this NLS
      mutation (NLSm) replicates less efficiently as wild-type. These data strongly
      suggested that the nuclear import of VP19C is required for efficient HSV-1
      production.

PMID- 22622330
TI  - Protein B5 is required on extracellular enveloped vaccinia virus for repulsion of
      superinfecting virions.
AB  - Vaccinia virus (VACV) spreads across cell monolayers fourfold faster than
      predicted from its replication kinetics. Early after infection, infected cells
      repulse some superinfecting extracellular enveloped virus (EEV) particles by the
      formation of actin tails from the cell surface, thereby causing accelerated
      spread to uninfected cells. This strategy requires the expression of two viral
      proteins, A33 and A36, on the surface of infected cells and upon contact with EEV
      this complex induces actin polymerization. Here we have studied this phenomenon
      further and investigated whether A33 and A36 expression in cell lines causes an
      increase in VACV plaque size, whether these proteins are able to block
      superinfection by EEV, and which protein(s) on the EEV surface are required to
      initiate the formation of actin tails from infected cells. Data presented show
      that VACV plaque size was not increased by expression of A33 and A36, and these
      proteins did not block entry of the majority of EEV binding to these cells. In
      contrast, expression of proteins A56 and K2 inhibited entry of both EEV and
      intracellular mature virus. Lastly, VACV protein B5 was required on EEV to induce
      the formation of actin tails at the surface of cells expressing A33 and A36, and
      B5 short consensus repeat 4 is critical for this induction.

PMID- 22622331
TI  - Evaluation of a candidate International Standard for Meningococcal Group C
      polysaccharide.
AB  - Meningococcal group C (MenC) plain polysaccharide (PS) and conjugate vaccines are
      primarily evaluated by physicochemical methods to ensure that batches are
      consistently manufactured. As different assays are employed to quantify the MenC
      PS content of final formulations and bulk intermediaries, there is a need for an
      International MenC PS Standard to calibrate internal references used in the
      different laboratories. Twelve laboratories from nine different countries
      participated in a collaborative study to determine the MenC PS content of a
      candidate International Standard MenC PS preparation (08/214) and to assess its
      suitability. On the basis of the results from this study the candidate standard
      08/214 was established as an International Standard for the quantification of
      MenC PS content in vaccines and components. It has a content of 1.192 +/- 0.192
      mg MenC PS/ampoule (expanded uncertainty with coverage factor of k = 2.365
      corresponding to a 95% level of confidence), as determined by the resorcinol
      assays carried out by eight of the participating laboratories. The standard is
      available from The National Institute of Biological Standards and Control who act
      as guardians and distributors of the material under the auspices of WHO.

PMID- 22622332
TI  - C5L2 receptor disruption enhances the development of diet-induced insulin
      resistance in mice.
AB  - INTRODUCTION: Acylation stimulating protein (ASP) is a hormone secreted by the
      adipose tissue that has been shown to increase triglyceride storage and glucose
      transport in adipocytes. These effects are mediated by C5L2 receptor, which has
      also been associated with inflammatory effects. C5L2 deficient mice on a low-fat
      diet are hyperphagic yet lean due to increased energy expenditure. The present
      study assessed insulin sensitivity and metabolic and inflammatory changes in
      C5L2KO mice vs WT in diet-induced obesity. METHODS: We placed C5L2KO and WT mice
      on a diabetogenic diet for 12 weeks and examined in vivo and ex vivo metabolism.
      RESULTS: C5L2KO mice on a diabetogenic diet exhibit decreased insulin
      sensitivity. Whole body substrate partitioning is evidenced through increased
      glucose uptake by the liver and decreased uptake by adipose tissue and skeletal
      muscle. Lipid content of both liver and skeletal muscle was higher in C5L2KO mice
      vs WT. Furthermore, elevated levels of macrophage markers were found in adipose
      tissue, liver and skeletal muscle of C5L2KO mice vs WT. Several inflammatory
      cytokines such as IL-6, MIP-1alpha and KC were also elevated in plasma of C5L2KO
      mice vs WT. CONCLUSIONS: Overall, we demonstrated that C5L2KO mice fed a
      diabetogenic diet develop more severe insulin resistance than WT mice through
      altered substrate partitioning, ectopic fat deposition and a pro-inflammatory
      phenotype.

PMID- 22622333
TI  - Efficacy of vasectomy reversal according to patency for the surgical treatment of
      postvasectomy pain syndrome.
AB  - This study was conducted to assess outcomes (according to patency) of vasectomy
      reversal (VR) in qualified patients with postvasectomy pain syndrome (PVPS). A
      total of 32 patients with PVPS undergoing VR between January 2000 and May 2010
      were examined retrospectively. Of these, 68.8% (22/32) completed a study
      questionnaire, either onsite at the outpatient clinic or via telephone interview.
      Preoperative clinical findings, preoperative and postoperative visual analogue
      scale (VAS) pain scores, patency and pregnancy rate and overall patient
      satisfaction were analyzed. For the latter, a four-point rating of (1) cure, (2)
      improvement, (3) no change or (4) recurrence was used. The mean age was 45.09+/
      4.42 years and the mean period of follow-up was 3.22 years (0.74-7.41). Patency
      rates were 68.2% (15/22) and pregnancy rates were 36.4% (8/22). The mean VAS was
      6.64+/-1.00 preoperatively and 1.14+/-0.71 postoperatively (P<0.001). The
      difference in the mean preoperative and postoperative VAS was 6.00+/-1.25 (4-8)
      in the patency group and 4.43+/-0.98 (3-6) in the no patency group (P=0.011). A
      significant difference in procedural satisfaction with surgical outcome was
      observed between patency and no patency groups (P=0.014). In conclusion, in PVPS
      patients requiring VR, a significant difference was observed between the patency
      and no patency groups in terms of pain reduction and the degree of patient
      procedural satisfaction.

PMID- 22622334
TI  - Retraction. Effects of exposure to a mobile phone on sexual behavior in adult
      male rabbit: an observational study.

PMID- 22622335
TI  - Variation of bacterial communities and expression of Toll-like receptor genes in
      the rumen of steers differing in susceptibility to subacute ruminal acidosis.
AB  - In order to determine differences in the ruminal bacterial community and host
      Toll-like receptor (TLR) gene expression of beef cattle with different
      susceptibility to acidosis, rumen papillae and content were collected from
      acidosis-susceptible (AS, n=3) and acidosis-resistant (AR, n=3) steers. The
      ruminal bacterial community was characterized using PCR-denaturing gradient gel
      electrophoresis (PCR-DGGE) and quantitative real time PCR (qRT-PCR) analysis.
      Global R analysis of bacterial profile similarity revealed that bacterial
      diversity was significantly different between AR and AS groups for both rumen
      content (P=0.001) and epithelial (P=0.002) communities. The copy number of total
      bacterial 16S rRNA genes in content of AS steers was 10-fold higher than that of
      AR steers, and the copy number of total 16S rRNA genes of epimural bacteria in AR
      steers was positively correlated with ruminal pH (r=0.59, P=0.04), and negatively
      correlated with total VFA concentration (r=-0.59, P=0.05). The expressions of
      host TLR2 and 4 genes were significantly higher in AR steers compared to those in
      AS steers. These findings enhance our understanding about the ruminal microbial
      ecology and host gene expression changes that may be useful in the prevention of
      ruminal acidosis.

PMID- 22622336
TI  - Assessment of the antifungal susceptibility of Malassezia pachydermatis in
      various media using a CLSI protocol.
AB  - The microdilution antifungal method (CLSI BMD, M27-A3) was used for testing the
      antifungal susceptibility of Malassezia species. However, optimal broth media
      that allow sufficient growth of M. pachydermatitis and produce reliable and
      reproducible MICs using the CLSI BMD protocol are yet to be established. In this
      study, the susceptibility of M. pachydermatis isolates to ketoconazole (KTZ),
      itraconazole (ITZ) and fluconazole (FLZ) was evaluated in vitro by the CLSI BMD
      test using Christensen's urea broth (CUB) and mRPMI 1640 containing lipid
      supplementation, Sabouraud dextrose broth with 1% tween 80 (SDB), and Dixon broth
      (DXB). A FLZ-resistant M. pachydermatis was generated in vitro and tested under
      the same conditions. A good growth of M. pachydermatis incubated for 48 and 72 h,
      respectively, was observed in CUB, SDB and DXB and not in mRPMI 1640 (p<0.001).
      No statistically significant differences were detected between the MIC values
      registered after 48 h and 72 h incubation. ITZ displayed lower MIC values than
      KTZ and FLZ regardless of the media employed. A large number of FLZ-resistant
      Malassezia strains (86.6%) was observed using DXB. A MIC>64 mg/L was observed
      only when the FLZ-resistant M. pachydermatis isolate was tested in SDB. Based on
      the results obtained herein, culture in SDB, stock inoculum suspensions of 1-5 *
      10(6)CFU/ml, and an incubation time of 48 h are proposed as optimal conditions
      for the evaluation of the in vitro antifungal susceptibility of M. pachydermatis
      using a modified CLSI BMD protocol.

PMID- 22622337
TI  - Subtilase cytotoxin encoding genes are present in human, sheep and deer intimin
      negative, Shiga toxin-producing Escherichia coli O128:H2.
AB  - Shiga toxin-producing Escherichia coli (STEC) O128:H2 is recognised worldwide to
      be an important non-O157 STEC associated with human illness and in particular
      with causing haemolytic uraemic syndrome. This serotype is commonly isolated from
      sheep and is being increasingly isolated from deer. We determined the virulence
      profile and genetic relationships of one human, six sheep and five deer intimin
      negative STEC O128:H2 strains isolated in Spain over a 7-year period. Our goals
      were to establish the presence of other virulence-associated factors, such as
      SubAB, in intimin-negative STEC O128:H2 strains involved in human disease and in
      that case, to determine if sheep and/or deer represent a reservoir of SubAB
      positive STEC O128:H2. All the strains lacked the eae gene and carried subtilase
      cytotoxin (SubAB) encoding genes (subAB) and tia genes, but not saa gene,
      suggesting the presence of the recently identified new variant of SubAB, encoded
      on a putative pathogenicity island together with tia. We report for the first
      time the presence of subtilase cytotoxin encoding genes in intimin-negative STEC
      O128:H2 strains pathogenic for humans and how this finding might explain their
      clinical relevance despite neither carrying eae nor stx subtypes associated with
      severe clinical outcomes, but only stx1c and stx2b. Multilocus sequence typing
      analysis revealed that STEC O128:H2 strains from sheep and deer belong to the
      clonal lineage of STEC O128:H2 strains involved in diarrhoeal and haemorrhagic
      diseases in humans. Our results indicate that sheep and deer represent a
      reservoir of SubAB-positive STEC O128:H2 strains and thus a potential source of
      human infection.

PMID- 22622338
TI  - Use of amitriptyline cream in the management of entry dyspareunia due to provoked
      vestibulodynia.
AB  - OBJECTIVE: This study aimed to evaluate the effectiveness of topical
      amitriptyline 2% in sorbolene (cetomacrogol aqueous) cream in the management of
      patients with entry dyspareunia caused by provoked vestibulodynia. MATERIALS AND
      METHODS: A prospective study of 150 patients presenting with entry dyspareunia to
      a private gynecologist (R.P.) was undertaken during a 12-month period. Provoked
      vestibulodynia was diagnosed by the presence of pinpoint tenderness confined to
      the vulvar vestibule. Most patients (102) had purely provoked vestibulodynia,
      whereas 48 had both provoked and unprovoked pain. There were 7 patients with
      grade 1 dyspareunia (intercourse always painful but only occasionally preventing
      penetration), 83 patients with grade 2 (intercourse always painful preventing
      penetration on most occasions), and 60 patients with grade 3 (apareunic).
      Questionnaires were evaluated before and 3 months after commencement of
      treatment. No control group using placebo was studied because of the private
      practice setting. RESULTS: Duration of symptoms varied from 1 to 30 years, the
      mean being 4.7 years. There was no response in 66 patients (44%). Of these, 16
      patients ceased treatment early because of local skin irritation and hence were
      regarded as treatment failures. The 84 patients (56%) that responded were divided
      into 3 groups as follows: (i) 25 with a slight but noticeable improvement; (ii)
      44 with a moderate degree of improvement; and (iii) 15 with an excellent
      response, describing intercourse as comfortable and pain free (10% of the total
      study group). Most patients in all 3 groups elected to continue application of
      the cream after completion of the study. The response rate was similar (48%) in
      the subgroup that also had unprovoked vestibulodynia. There was no difference in
      the response rate according to parity. The response rate was also similar in
      patients who had previously taken oral amitriptyline unsuccessfully. In these 44
      patients, the overall response rate was 59%. CONCLUSIONS: Topical amitriptyline
      cream should be considered for first-line treatment in the management of patients
      with provoked vestibulodynia causing entry dyspareunia. The response rate is
      reasonable (56%), and it eliminates the problems with systemic administration,
      namely, drowsiness and the difficulty patients have in accepting antidepressant
      medication for their condition.

PMID- 22622339
TI  - Rates of self-reported urinary, gastrointestinal, and pain comorbidities in women
      with vulvar lichen sclerosus.
AB  - OBJECTIVE: The study aimed to determine the prevalences of comorbid disorders in
      women with vulvar lichen sclerosus. MATERIALS AND METHODS: A retrospective review
      of self-administered questionnaires regarding the health history of 308 women
      with lichen sclerosus seen at a vulvar clinic between 2006 and 2011 was
      performed. Responses to questions about urinary (overactive bladder [OAB],
      urinary incontinence [UI], and stress UI), gastrointestinal (inflammatory bowel
      diseases, constipation, and irritable bowel syndrome), thyroid dysfunction and
      pain (interstitial cystitis, fibromyalgia, temporomandibular joint disorder, and
      vulvar pain) disorders were collected. The percentage of subjects self-reporting
      each comorbidity was compared with the published prevalence in the general
      population using a single-value binomial test. RESULTS: Subject demographics
      (data presented as median [range] or percentage): age, 56.4 years (20.0-92.5);
      body mass index, 27.5 kg/m2 (17.4-53.1); parity 2 (0-10); white, 92.9%; and
      biopsy proven 65.6%. Prevalences of self-reported comorbidities in our subjects
      are as follows: OAB, 15.3%; UI, 38.6%; stress UI, 27.9%; inflammatory bowel
      diseases, 1.9%; constipation, 32.5%; irritable bowel syndrome, 19.5%; thyroid
      dysfunction, 33.1%; interstitial cystitis, 2.6%; fibromyalgia, 9.1%;
      temporomandibular joint disorder, 13.0%; and vulvar pain, 83.1%. The prevalence
      of each disorder is significantly different from that in the general population,
      with all p values <= .02. CONCLUSIONS: Vulvar lichen sclerosus is associated with
      numerous bladder, bowel, and pain comorbidities. The prevalences of all of these
      disorders are higher in our subjects than the general population except OAB,
      which we find at approximately one third of the general population. Patients with
      lichen sclerosus should be screened for comorbidities that may affect their
      health and/or quality of life.

PMID- 22622341
TI  - 2011 ISSVD Terminology and classification of vulvar dermatological disorders: an
      approach to clinical diagnosis.
AB  - OBJECTIVE: The study aimed to formulate an easy clinical approach that may be
      used by clinicians of all backgrounds to diagnose vulvar dermatological
      disorders. MATERIALS AND METHODS: The International Society for the Study of
      Vulvovaginal Disease appointed a committee with multinational members from the
      fields of dermatology, gynecology, and pathology and charged the committee to
      formulate a clinically based terminology and classification of vulvar
      dermatological disorders. The committee carried out its work by way of multiple
      rounds of e-mails extending over almost 2 year's time. RESULTS: The committee was
      able to formulate a consensus report containing terminology, classification, and
      a step-wise approach to clinical diagnosis of vulvar dermatological disorders.
      This report was presented and approved by the International Society for the Study
      of Vulvovaginal Disease at the XXI International Congress held in Paris, France,
      on September 3 to 8, 2011. CONCLUSIONS: The authors believe that the approach to
      terminology and classification as well as clinical diagnosis contained in this
      article allows clinicians to make highly accurate diagnoses of vulvar
      dermatological disorders within the clinical setting. This, in turn, will reduce
      the need for referrals and will improve the care for women with most vulvar
      disorders.

PMID- 22622340
TI  - The challenge of follow-up in a low-income colposcopy clinic:  characteristics
      associated with noncompliance in high-risk populations.
AB  - OBJECTIVE: The study aimed to identify sociodemographic and disease-specific
      factors associated with follow-up in an inner-city multiethnic colposcopy clinic.
      MATERIALS AND METHODS: All charts of patients referred to colposcopy clinic for
      abnormal cervical cytology and/or high-risk human papillomavirus infections to
      the University of California, Irvine, Colposcopy Clinic in Santa Ana from
      November 2006 to December 2007 were reviewed. Compliance was defined as at least
      1 follow-up evaluation within 3 to 14 months from initial colposcopy appointment.
      To determine compliance, the following factors were evaluated in a multivariate
      analysis: race, age, spoken language, insurance status, annual income, marital
      status, referral cytology, histology, and pregnancy status. RESULTS: Among the
      1,046 scheduled appointments, 50% were attended. Of the patients, 458 with a
      minimum of 14 months of follow-up were included. The mean (SD) age of these
      patients was 31.0 (10.7) years. 58% were white and 55% spoke Spanish. A total of
      248 patients (54%) had appropriately timed repeat testing, whereas 210 (46%)
      failed to return within 14 months. In univariate analysis, women who were
      referred from outside the clinic, single, younger than 40 years, and with self
      pay or government-funded insurance were more likely to be noncompliant although
      this was not statistically significant. In multivariate analysis, referral from
      outside the clinic, self-pay, or government-funded insurance, Spanish-speaking,
      and single marital status were all significantly associated with noncompliance.
      Although cervical intraepithelial neoplasia 2 or 3 was not associated with
      noncompliance, 45% of women with cervical intraepithelial neoplasia 2 or 3 still
      did not comply with recommendations. CONCLUSIONS: This inner-city clinic is
      perhaps successful at maintaining compliance for women at highest risk for
      cervical cancer when the triage originates from within the clinic and when the
      patient is married, English-speaking, and privately insured. However, reasons for
      those patients at highest risk for noncompliance in this clinic may need to be
      better characterized.

PMID- 22622342
TI  - Prevalence and associations of domestic violence at an Australian colposcopy
      clinic.
AB  - OBJECTIVE: Domestic violence is associated with significant mortality and
      morbidity including gynecological morbidity. We report the prevalence and
      associations of domestic violence in an Australian colposcopy service. MATERIALS
      AND METHODS: A prospective study was performed from consecutive patients
      attending colposcopy clinics at a major metropolitan hospital in Australia. Key
      outcomes were the prevalence of intimate partner violence and its key demographic
      associations. RESULTS: Consent was obtained from 574 and domestic violence status
      was ascertained in 566 of 581 women approached. Overall, 33% of responders
      reported violence within 12 months. In 14.5%, the female reported being sole
      recipient of violence; in a further 16.6%, violence was bidirectional, and in
      1.9% of cases, a woman was the sole perpetrator. Key associations of violence
      were younger age at presentation (32 vs 35 y; p = .01), higher rates of smoking
      (51.3% vs 38.2%; p = .0004), higher rates of housing instability (32.2% vs 12.2%;
      p < .0001), a positive Beck Depression Inventory screen (50.0% vs 24.6%; p <
      .0001), and higher rates of default to initial attendance (15.5% vs 4.7%, p <
      .0001). CONCLUSIONS: Domestic violence is common in women presenting to
      colposcopy services and may be associated with poor housing stability and higher
      default rates.

PMID- 22622343
TI  - Utility of random cervical biopsy and endocervical curettage in a low-risk
      population.
AB  - OBJECTIVE: The study aimed to determine the increase in the yield of cervical
      intraepithelial neoplasia 3 (CIN 3) or cancer (CIN 3+) from random cervical
      biopsy in quadrants without visible lesions and endocervical curettage (ECC) in a
      low-prevalence setting. MATERIALS AND METHODS: Random biopsy and ECC (unless
      pregnant) have been obtained in the colposcopy clinic of the Southern California
      Permanente Medical Group (SCPMG)-Fontana since 2004. We reviewed the colposcopy
      experience of SCPMG-Fontana for January 1, 2007, to December 31, 2009, to
      determine the method of diagnosis of CIN 3+. RESULTS: Between January 1, 2007,
      and December 31, 2009, 4677 women with median age 32 years had 4932 colposcopies
      in the SCPMG-Fontana colposcopy clinics. Cervical intraepithelial neoplasia 3+
      was diagnosed in 295 women. Cervical biopsy detected 64.4% of CIN 3+; ECC
      diagnosed 5.1%; loop electrocautery excision procedure (LEEP) or cervical
      conization for cervical biopsy and/or ECC of CIN 2 diagnosed 27.8%; LEEP for the
      cytology of high-grade squamous intraepithelial lesion with cervical biopsy
      result of negative or CIN 1 diagnosed 1.4%; and LEEP, cervical conization, or
      biopsy in follow-up of CIN 2 diagnosed 1.4%. Sixty-one of the 295 cases of CIN 3+
      (20.7%) were diagnosed after evaluation of random cervical biopsy and/or ECC of
      CIN 2+. CONCLUSIONS: Random biopsy in cervical quadrants without visible lesions
      and ECC increased the yield of CIN 3+ in this low-risk colposcopy setting.
      Endocervical curettage can be omitted in women younger than 25 years.

PMID- 22622344
TI  - Mucosal lichen planus, a systemic disease requiring multidisciplinary care:  a
      cross-sectional clinical review from a multidisciplinary perspective.
AB  - OBJECTIVE: This study aimed to emphasize the importance of seeing mucosal lichen
      planus (LP) as a systemic disease and not an isolated oral or genital disease and
      to analyze the proportion of thyroid antibodies among patients with multimucosal
      LP. MATERIALS AND METHODS: All patients examined by the authors and diagnosed
      with mucosal LP within 1 year were consecutively included. Full medical histories
      were collected with special emphasis on autoimmune and thyroid diseases. Sera
      were analyzed for thyroid antibodies and underwent serologic test for herpes
      virus. The control group comprised 83 healthy volunteers matched regarding sex
      and age. RESULTS: Of the patients, 120 were included, 89 (74%) of whom were women
      and 31 (26%) were men. The vast majority of the patients had multifocal lesions,
      whereas oral lesions solely were found in 28% of women and 36% of men. Of the
      patients, 28% had at least 1 additional autoimmune disease. Approximately half of
      the women were treated with levothyroxine owing to thyroid disease. Antibodies
      against herpes simplex virus were found in 60% of the patients and 44% of the
      controls (p < .03). CONCLUSIONS: Lichen planus with mucosal involvement should be
      considered and taken care of as a systemic disease and not as an isolated oral
      and/or genital lichen. Contradictory to many former reports, most of our patients
      have a multimucosal disease that emphasizes the need for a multidisciplinary
      clinic to get optimal care and treatment.

PMID- 22622345
TI  - Topical loteprednol etabonate 0.5 % for treatment of vernal keratoconjunctivitis:
      efficacy and safety.
AB  - PURPOSE: To evaluate the efficacy and safety of loteprednol etabonate (LE) 0.5 %
      in vernal keratoconjunctivitis (VKC) patients compared to prednisolone and
      fluorometholone. METHODS: The patients were randomized into three groups: the
      loteprednol group, prednisolone group and fluorometholone group. Medications were
      administered four times daily, for a total of 28 days. Before starting treatment
      and at each visit thereafter, the major symptoms and signs of VKC were recorded
      and graded as 0 (none), 1 (mild), 2 (moderate) or 3 (severe). Adverse event
      reports including elevation of intraocular pressure (IOP) were recorded. RESULTS:
      There were no significant differences among the groups concerning baseline mean
      scores of signs and symptoms, which gradually improved in all except for pannus
      formation in the fluorometholone group. However, all signs and symptoms (except
      for chemosis) were significantly less improved in the eyes of the fluorometholone
      group compared with the other groups at each control visit. There was significant
      IOP elevation after the day 3 visit in the prednisolone group only. CONCLUSION:
      LE was as effective as prednisolone and more effective than fluorometholone, and
      it had no side effects during the short-term treatment of VKC patients.

PMID- 22622346
TI  - Variability and accuracy of coronary CT angiography including use of iterative
      reconstruction algorithms for plaque burden assessment as compared with
      intravascular ultrasound-an ex vivo study.
AB  - OBJECTIVES: To systematically assess inter-technique and inter-/intra-reader
      variability of coronary CT angiography (CTA) to measure plaque burden compared
      with intravascular ultrasound (IVUS) and to determine whether iterative
      reconstruction algorithms affect variability. METHODS: IVUS and CTA data were
      acquired from nine human coronary arteries ex vivo. CT images were reconstructed
      using filtered back projection (FBPR) and iterative reconstruction algorithms:
      adaptive-statistical (ASIR) and model-based (MBIR). After co-registration of 284
      cross-sections between IVUS and CTA, two readers manually delineated the cross
      sectional plaque area in all images presented in random order. RESULTS: Average
      plaque burden by IVUS was 63.7 +/- 10.7% and correlated significantly with all
      CTA measurements (r = 0.45-0.52; P < 0.001), while CTA overestimated the burden
      by 10 +/- 10%. There were no significant differences among FBPR, ASIR and MBIR (P
      > 0.05). Increased overestimation was associated with smaller plaques,
      eccentricity and calcification (P < 0.001). Reproducibility of plaque burden by
      CTA and IVUS datasets was excellent with a low mean intra-/inter-reader
      variability of <1/<4% for CTA and <0.5/<1% for IVUS respectively (P < 0.05) with
      no significant difference between CT reconstruction algorithms (P > 0.05).
      CONCLUSION: In ex vivo coronary arteries, plaque burden by coronary CTA had
      extremely low inter-/intra-reader variability and correlated significantly with
      IVUS measurements. Accuracy as well as reader reliability were independent of CT
      image reconstruction algorithm. KEY POINTS: * IVUS is deemed the gold standard in
      vivo coronary plaque assessment * But coronary CT angiography findings correlate
      strongly with IVUS results * Coronary CT angiography now allows plaque
      quantification close to IVUS * Iterative image reconstruction algorithms do not
      alter accuracy or reproducibility * Plaque quantification is more challenging in
      smaller eccentric calcified lesions.

PMID- 22622347
TI  - Differentiation of neoplastic from bland macroscopic portal vein thrombi using
      dual-energy spectral CT imaging: a pilot study.
AB  - OBJECTIVES: To assess the feasibility and value of dual-energy spectral computed
      tomography (DESCT) imaging for differentiating neoplastic from bland macroscopic
      portal vein (PV) thrombi. METHODS: Computed tomography (CT) images of 44 patients
      with macroscopic PV thrombus (bland group, n = 16; neoplastic group, n = 28) were
      reviewed. Iodine-based material decomposition images in the portal venous phase
      were reconstructed to compare the iodine indices between groups, including
      thrombus iodine density (I (T)), thrombus-aorta iodine density ratio (I (T)/I
      (A)), and thrombus-PV iodine density ratio (I (T)/I (P)). Differential diagnostic
      performances of DESCT were calculated in the subgroup of 21 patients with
      histopathological evidence (bland group, n = 12; neoplastic group, n = 9).
      RESULTS: The iodine indices of the neoplastic group were significantly higher
      than those in the bland group (P < 0.001). A threshold I (T) of 1.14 mg/mL, I
      (T)/I (A) of 0.17, and I (T)/I (P) of 0.17 in the portal venous phase yielded 100
      %, 88.9 %, and 100 % sensitivity, and 91.7 %, 91.7 %, and 83.3 % specificity,
      respectively, in differentiating neoplastic from bland PV thrombi. CONCLUSIONS:
      DESCT imaging with quantification of thrombus iodine density in the portal venous
      phase appears to be a promising new method for distinguishing neoplastic from
      bland macroscopic PV thrombi. KEY POINTS: * Differentiating the nature of portal
      vein thrombus is of great clinical significance. * Iodine-based material
      decomposition imaging reflects iodine distribution after contrast media
      administration. * Dual-energy CT with iodine quantification can distinguish bland
      from neoplastic PV thrombi.

PMID- 22622348
TI  - ECG-gated computed tomography: a new role for patients with suspected aortic
      prosthetic valve endocarditis.
AB  - OBJECTIVES: The aim of this prospective study was to investigate the agreement in
      findings between ECG-gated CT and transoesophageal echocardiography (TEE) in
      patients with aortic prosthetic valve endocarditis (PVE). METHODS: Twenty-seven
      consecutive patients with PVE underwent 64-slice ECG-gated CT and TEE and the
      results were compared. Imaging was compared with surgical findings (surgery was
      performed in 16 patients). RESULTS: TEE suggested the presence of PVE in all
      patients [thickened aortic wall (n = 17), vegetation (n = 13), abscess (n = 16),
      valvular dehiscence (n = 10)]. ECG-gated CT was positive in 25 patients (93 %)
      [thickened aortic wall (n = 19), vegetation (n = 7), abscess (n = 18), valvular
      dehiscence (n = 7)]. The strength of agreement [kappa (95 % CI)] between ECG
      gated CT and TEE was very good for thickened wall [0.83 (0.62-1.0)], good for
      abscess [0.68 (0.40-0.97)] and dehiscence [0.75 (0.48-1.0)], and moderate for
      vegetation [0.55 (0.26-0.88)]. The agreement was good between surgical findings
      (abscess, vegetation and dehiscence) and imaging for ECG-gated CT [0.66 (0.49
      0.87)] and TEE [0.79 (0.62-0.96)] and very good for the combination of ECG-gated
      CT and TEE [0.88 (0.74-1.0)]. CONCLUSION: Our results indicate that ECG-gated CT
      has comparable diagnostic performance to TEE and may be a valuable complement in
      the preoperative evaluation of patients with aortic PVE.

PMID- 22622350
TI  - Zirconium complexes incorporated with asymmetrical tridentate pincer type mono-
      and di-anionic pyrrolyl ligands: mechanism and reactivity as catalytic
      precursors.
AB  - The reactions of Zr(NR(2))(4) (1, R = Me; 2, R = Et) with an asymmetrical
      tridentate pincer type pyrrole ligand precursor [C(4)H(2)NH(2-CH(2)NH(t)Bu)(5
      CH(2)NMe(2))] and treatment of the derivatives with either PhNCS or PhNCO have
      been carried out and characterized. Reacting Zr(NR(2))(4) (1, R = Me; 2, R = Et)
      with [C(4)H(2)NH(2-CH(2)NH(t)Bu)(5-CH(2)NMe(2))] generates Zr[C(4)H(2)N(2
      CH(2)N(t)Bu)(5-CH(2)NMe(2))](NR(2))(2) (3, R = Me; 4, R = Et) in high yield along
      with the elimination of 2 equiv of dimethylamine or diethylamine, respectively.
      Interestingly, while changing the solvent from Et(2)O to CH(2)Cl(2), the complex
      Zr[C(4)H(2)N(2-CH(2)N(t)Bu)(5-CH(2)NMe(2))][C(4)H(2)N(2-CH(2)NH(t)Bu)(5
      CH(2)NMe(2))]Cl (5) is produced by undergoing C-Cl bond cleavage. Furthermore,
      reaction of either 3 or 4 with 1 or 2 equiv of PhNCS or PhNCO yields
      Zr[C(4)H(2)N(2-CH(2)N(t)Bu)(5-CH(2)NMe(2))](NMe(2))[PhNC(NMe(2))S] (6),
      Zr[C(4)H(2)N(2-CH(2)N(t)Bu)(5-CH(2)NMe(2))](NEt(2))[PhNC(NEt(2))O] (7) and
      Zr[C(4)H(2)N(2-CH(2)NH(t)Bu)(5-CH(2)NMe(2))][PhNC(NEt(2))O](3) (8), respectively.
      All the aforementioned complexes were characterized by (1)H and (13)C NMR
      spectrometry and the molecular structures of 5, 6, and 8 have been determined by
      single-crystal X-ray diffractometry. Complexes 4, 5, and 7 initiated the ethylene
      polymerization in the presence of MAO as the co-catalyst.

PMID- 22622349
TI  - Increased rectal microbial richness is associated with the presence of colorectal
      adenomas in humans.
AB  - Differences in the composition of the gut microbial community have been
      associated with diseases such as obesity, Crohn's disease, ulcerative colitis and
      colorectal cancer (CRC). We used 454 titanium pyrosequencing of the V1-V2 region
      of the 16S rRNA gene to characterize adherent bacterial communities in mucosal
      biopsy samples from 33 subjects with adenomas and 38 subjects without adenomas
      (controls). Biopsy samples from subjects with adenomas had greater numbers of
      bacteria from 87 taxa than controls; only 5 taxa were more abundant in control
      samples. The magnitude of the differences in the distal gut microbiota between
      patients with adenomas and controls was more pronounced than that of any other
      clinical parameters including obesity, diet or family history of CRC. This
      suggests that sequence analysis of the microbiota could be used to identify
      patients at risk for developing adenomas.

PMID- 22622351
TI  - Synthesis of isochromenones and oxepines via Pd-catalyzed cascade cyclization of
      alkynes and benzynes involving C-H activation.
AB  - A new method for the synthesis of various isochromen-6-ones and phenanthro[1,10
      bc]oxepines via a palladium-catalyzed cascade carbocyclization of 2-iodobenzyl-3
      phenylpropiolates and 1-iodo-2-(2-(phenylethynyl)benzyloxy)benzenes with arynes
      is described. The reactions involve interesting biscarbocyclization of alkynes
      and benzynes and C-H bond activation.

PMID- 22622352
TI  - Planned caesarean in the interventional radiology cath lab to enable immediate
      uterine artery embolization for the conservative treatment of placenta accreta.
AB  - AIM: To evaluate the feasibility and efficacy of routine uterine artery
      embolization (UAE) immediately after planned caesareans performed in the cath lab
      for conservative treatment of placenta accreta. MATERIALS AND METHODS: A
      retrospective study included all patients who had a planned caesarean in the cath
      lab for conservative treatment of placenta accreta at Angers University Hospital,
      which is a tertiary care centre, from April 2001 to September 2010. Twelve
      patients underwent UAE immediately after caesarean with the placenta left
      partially or totally in situ. The success rate of embolization, blood loss, and
      complications were reported. RESULTS: Diagnosis of abnormal placentation was
      confirmed by caesarean findings in 14 cases. Four patients had a percreta form
      with bladder invasion. In seven cases blood loss was insignificant and UAE was
      prophylactic; no secondary haemorrhage was observed in this group. Postpartum
      haemorrhage occurred in five cases: control of immediate postpartum bleeding by
      embolization was successful in three and failed in two leading to hysterectomy.
      In one case uterine necrosis occurred 6 weeks after embolization, requiring a
      hysterectomy. Delayed complications resulted in hysterectomy and partial bladder
      resection 3 months after delivery for one of the patients with placenta percreta.
      CONCLUSION: UAE immediately after a caesarean performed in the cath lab is a
      feasible therapeutic option for conservative treatment of placenta accreta.
      Advantages include reducing stress and risks associated with transferring women
      with potentially unstable haemodynamics.

PMID- 22622353
TI  - Malposition of urinary catheter managed by image-guided intervention.

PMID- 22622354
TI  - Neoplastic and proliferative disorders of the perinephric space.
AB  - The perinephric space is a well-marginated central compartment of the
      retroperitoneum, located between the anterior and posterior pararenal spaces.
      Various neoplastic and proliferative disorders can affect the perinephric space,
      and there is a wide array of imaging findings. Although many perinephric lesions
      may extend directly from the kidney and adrenal gland, other lesions occur in the
      perinephric space due to haematogenous spread, as part of a systemic disease, or
      by extension from an adjacent retroperitoneal compartment. Imaging plays a
      pivotal role in the diagnosis of perinephric diseases, as many of the disease
      processes affecting this space will not result in clinical signs or symptoms
      until the disease is at an advanced stage. Despite the often shared non-specific
      clinical and imaging findings among these disease processes, application of a
      categorical differential diagnosis based on the imaging characteristics will
      serve to narrow the differential diagnosis and direct further evaluation and
      treatment. In this article, the lesions have been categorized as soft-tissue rind
      [nephroblastomatosis, fibrosis, Erdheim-Chester disease (ECD), extramedullary
      haematopoiesis, lymphoma, infiltrating metastases], focal solid lesions
      (extension of renal or adrenal malignancies, melanoma metastases, treated
      lymphoma), fat-containing lesions (angiomyolipoma, liposarcoma, myelolipoma), and
      cystic lesions (lymphangiomas, abscesses). The aim of this article is to
      demonstrate and describe the key imaging features of several neoplastic and
      proliferative disorders that affect the perinephric space.

PMID- 22622355
TI  - Science, practice and mythology: a definition and examination of the implications
      of scientism in medicine.
AB  - Scientism is a philosophy which purports to define what the world 'really is'. It
      adopts what the philosopher Thomas Nagel called 'an epistemological criterion of
      reality', defining what is real as that which can be discovered by certain quite
      specific methods of investigation. As a consequence all features of experience
      not revealed by those methods are deemed 'subjective' in a way that suggests they
      are either not real, or lie beyond the scope of meaningful rational inquiry. This
      devalues capacities that (we argue) are in fact essential components of good
      reasoning and virtuous practice. Ultimately, the implications of scientism for
      statements of value undermine value-judgements essential for science itself to
      have a sound basis. Scientism has implications, therefore, for ontology,
      epistemology and also for which claims we can assert as objective truths about
      the world. Adopting scientism as a world view will have consequences for
      reasoning and decision-making in clinical and other contexts. We analyse the
      implications of this approach and conclude that we need to reject scientism if we
      are to avoid stifling virtuous practice and to develop richer conceptions of
      human reasoning.

PMID- 22622356
TI  - Targeted delivery to single cells in precisely controlled microenvironments.
AB  - The heterogeneous nature of cells can be an issue for in vitro analysis of cell
      function due to cell type differences within a population. Observations are most
      often averaged and dependent on the homogeneity or lack thereof for most cell
      types. Patterning of features at the sub-cellular scale (< 10 MUm) allows for
      single cell manipulation. Additionally, the ability to pattern multiple materials
      simultaneously with nanoscale precision enables facile fabrication of multiplexed
      cellular microenvironment arrays. Here we use this ability to deliver different
      materials to single or few cells within hundreds of microns of each other on the
      same substrate. Calcein AM, Calcein Red AM and quantum dots are delivered to live
      single or few cells. This allows for exposing limited cell numbers to many well
      defined conditions, thus opening the possibility of single cell based assays.

PMID- 22622357
TI  - [Pediatric tracheotomy].
AB  - Tracheotomies are increasingly performed in the pediatric population in the
      context of long-term treatment. There are specific pediatric aspects that require
      attention: differences in the pediatric compared to adult anatomy, the necessity
      for later reconstruction and the negative impact on oral feeding and speech
      development. Caring for pediatric tracheostomy patients is more challenging
      compared to adult patients. This needs to be addressed by a dedicated team during
      both in- and outpatient treatment.

PMID- 22622358
TI  - Relation between biomarkers in exhaled breath condensate and internal exposure to
      metals from gas metal arc welding.
AB  - Concerning possible harmful components of welding fumes, besides gases and
      quantitative aspects of the respirable welding fumes, particle-inherent metal
      toxicity has to be considered.The objective of this study was to investigate the
      effect markers leukotriene B4 (LTB4),prostaglandin E2 (PGE2) and 8-isoprostane (8
      Iso PGF2alpha) as well as the acid-base balance(pH) in exhaled breath condensate
      (EBC) of 43 full-time gas metal arc welders (20 smokers) in relation to welding
      fume exposure. We observed different patterns of iron, chromium and nickel in
      respirable welding fumes and EBC. Welders with undetectable chromium in EBC(group
      A, n = 24) presented high iron and nickel concentrations. In this group, higher 8
      isoPGF2alpha and LTB4 concentrations could be revealed compared to welders with
      detectable chromium and low levels of both iron and nickel in EBC (group B): 8
      iso PGF2alpha443.3 pg mL-1 versus 247.2 pg mL-1; p = 0.001 and LTB4 30.5 pg mL-1
      versus 17.3 pgmL-1; p = 0.016. EBC-pH was more acid in samples of group B (6.52
      versus 6.82; p = 0.011).Overall, effect markers in welders were associated with
      iron concentrations in EBC according to smoking habits--non-smokers/smokers: LTB4
      (rs = 0.48; p = 0.02/rs = 0.21; p = 0.37),PGE2 (rs = 0.15; p = 0.59/rs = 0.47; p
      = 0.07), 8-iso PGF2alpha (rs = 0.18; p = 0.54/rs = 0.59;p = 0.06). Sampling of
      EBC in occupational research provides a matrix for the simultaneous monitoring of
      metal exposure and effects on target level. Our results suggest irritative
      effects in the airways of healthy welders. Further studies are necessary to
      assess whether these individual results might be used to identify welders at
      elevated risk for developing a respiratory disease.

PMID- 22622359
TI  - Transcriptional profiling of genes involved in embryogenic, non-embryogenic
      calluses and somatic embryogenesis of Valencia sweet orange by SSH-based
      microarray.
AB  - Somatic embryogenesis (SE) is a most promising technology that is used for in
      vitro germplasm conservation and genetic improvement via biotechnological
      approaches in citrus. Herein, three suppression subtractive hybridization (SSH)
      libraries were constructed using calluses of Citrus sinensis cv. 'Valencia' to
      explore the molecular mechanisms that underlie the SE in citrus. A total of 880
      unisequences were identified by microarray screening based on these three SSH
      libraries. Gene ontology analysis of the differentially expressed genes indicated
      that nucleolus associated regulation and biogenesis processes, hormone signal
      transduction, and stress factors might be involved in SE. Transcription factors
      might also play an important role. LEC1/B3 domain regulatory network genes (LEC1,
      L1L, FUS3, ABI3, and ABI5) were isolated in citrus SE. Some new transcription
      factors associated with citrus SE, like a B3 domain containing gene and HB4, were
      identified. To understand the influence of these isolated genes on SE competence,
      their expression profiles were compared among callus lines of seven citrus
      cultivars with different SE competence. The expression dynamics suggested that
      these genes could be necessary for the SE initiation and might play a role in
      embryogenic competence maintenance in different cultivars. On the basis of gene
      expression profiles, an overview of major physiological and biosynthesis
      processes at different developmental stages during citrus SE is presented. For
      the first time, these data provide a global resource for transcriptional events
      important for SE in citrus, and the specific genes offer new information for
      further investigation on citrus SE maintenance and development.

PMID- 22622360
TI  - Haplotype analysis of ESR2 in Japanese patients with spermatogenic failure.
AB  - The prevalence of spermatogenic failure (SF) has gradually increased during the
      past few decades at least in several countries. Although multiple factors would
      be involved in this phenomenon, one important factor would be excessive estrogen
      effects via estrogen receptors (ERs). Thus, we performed haplotype analysis of
      ESR2 encoding ERbeta in 125 Japanese SF patients and 119 age-matched control
      males, using single nucleotide polymorphisms (SNPs) 1-9 that are widely
      distributed on the ~120-kb genomic sequence of ESR2. Consequently, a linkage
      disequilibrium (LD) block was detected in an ~60-kb region encompassing SNPs 2-7
      in both groups, and four major estimated haplotypes were identified within the LD
      block. Furthermore, the most prevalent 'TGTAGA' haplotype was found to be
      significantly associated with SF, with the P-value obtained by the Cochran
      Armitage trend test (0.0029) being lower than that obtained by a 100 000-times
      permutation test (0.0038) to cope with the problem of multiple comparisons. The
      results, in conjunction with our previous data indicating lack of a
      susceptibility factor on ESR1 encoding ERalpha, imply that the specific 'TGTAGA'
      haplotype of ESR2 raises the susceptibility to the development of SF.

PMID- 22622361
TI  - Atypical hemolytic uremic syndrome and genetic aberrations in the complement
      factor H-related 5 gene.
AB  - Atypical hemolytic uremic syndrome (aHUS) is a severe renal disorder that is
      associated with mutations in genes encoding proteins of the alternative
      complement pathway. Previously, we identified pathogenic variations in genes
      encoding complement regulators (CFH, CFI and MCP) in our aHUS cohort. In this
      study, we screened for mutations in the alternative pathway regulator CFHR5 in 65
      aHUS patients by means of PCR on genomic DNA and sequence analysis. Potential
      pathogenicity of genetic alterations was determined by published data on CFHR5
      variants, evolutionary conservation and in silico mutation prediction programs.
      Detection of serum CFHR5 was performed by western blot analysis and enzyme-linked
      immunosorbent assay. A potentially pathogenic sequence variation was found in
      CFHR5 in three patients (4.6%). All variations were located in short consensus
      repeats that might be involved in binding to C3b, heparin or C-reactive protein.
      The identified CFHR5 mutations require functional studies to determine their
      relevance to aHUS, but they might be candidates for an altered genetic profile
      predisposing to the disease.

PMID- 22622362
TI  - Unilateral straight hair and congenital horner syndrome.
AB  - Congenital Horner syndrome is a rare disorder that accounts for less than 5% of
      all cases of Horner syndrome. Like Horner syndrome in general, it consists
      primarily of ptosis, miosis, and anhidrosis. Congenital Horner syndrome may
      manifest some special features such as iris heterochromia since the sympathetic
      nervous system is an essential component for the development and maintenance of
      eye color. We present 3 cases of unilateral straight hair in association with
      congenital Horner syndrome in which the patients had straight hair ipsilateral to
      the Horner syndrome, whereas on the contralateral side, it was curly, and we
      discuss possible mechanisms for this phenomenon.

PMID- 22622363
TI  - Vm24, a natural immunosuppressive peptide, potently and selectively blocks Kv1.3
      potassium channels of human T cells.
AB  - Blockade of Kv1.3 K(+) channels in T cells is a promising therapeutic approach
      for the treatment of autoimmune diseases such as multiple sclerosis and type 1
      diabetes mellitus. Vm24 (alpha-KTx 23.1) is a novel 36-residue Kv1.3-specific
      peptide isolated from the venom of the scorpion Vaejovis mexicanus smithi. Vm24
      inhibits Kv1.3 channels of human lymphocytes with high affinity (K(d) = 2.9 pM)
      and exhibits >1500-fold selectivity over other ion channels assayed. It inhibits
      the proliferation and Ca(2+) signaling of human T cells in vitro and reduces
      delayed-type hypersensitivity reactions in rats in vivo. Our results indicate
      that Vm24 has exceptional pharmacological properties that make it an excellent
      candidate for treatment of certain autoimmune diseases.

PMID- 22622364
TI  - Acute tryptophan depletion in accordance with body weight: influx of amino acids
      across the blood-brain barrier.
AB  - Acute tryptophan depletion (ATD) is a method of reducing central nervous
      serotonin (5-HT) synthesis in humans by administering an amino acid (AA) beverage
      lacking in tryptophan (TRP), the physiological precursor of 5-HT. However, to
      date, the use of conventional ATD protocols in children and adolescents was
      limited due to frequently observed side effects (e.g., vomiting and nausea). This
      study investigated the effects of diminished central nervous system 5-HT
      synthesis on plasma concentrations of relevant AAs and TRP influx into the brain
      in 24 healthy young adults using the ATD procedure Moja-De, a test protocol that
      has been used in preliminary research in youths. Twenty-four healthy participants
      received ATD and a TRP-balanced amino acid load (BAL) using a randomized double
      blind within-subject crossover design. Plasma concentrations of the relevant AAs
      that compete with TRP on the same transport system were assessed at baseline and
      90, 180, and 240 min after ATD/BAL intake. TRP influx across the blood-brain
      barrier was calculated using Michaelis-Menten kinetics with a correction for
      multiple substrate competition, indicating a significant decrease in TRP influx
      into the central nervous system under Moja-De. ATD Moja-De decreased TRP influx
      into the brain and central nervous system 5-HT synthesis safely and effectively
      and was well tolerated, allowing it to be used in children and adolescents.
      Future research into other secondary, compensatory effects induced by ATD in
      patients with neuropsychiatric disorders and healthy populations is needed. ATD
      Moja-De allows this type of research with a focus on a developmental viewpoint.

PMID- 22622365
TI  - CSF and clinical hallmarks of subcortical dementias: focus on DLB and PDD.
AB  - Dementia has become a relevant problem associated with the elderly in our
      countries. Increased interest in the field has yielded a copious literature, so
      far mostly centered on Alzheimer's dementia. Cerebrospinal fluid (CSF) analysis
      combined with neuropsychology, even in absence of neuroimaging, represents the
      gold standard to reach a diagnosis when cortical cognitive impairment prevails.
      In view of this, low levels of CSF amyloid peptides beta (Abeta) and high
      tau/Abeta protein ratio, despite prominent impairment of executive functions or
      concomitant vascular burden, facilitate the diagnosis of Alzheimer's disease.
      Conversely, an early cognitive impairment occurring in patients suffering from
      Parkinson's disease (PD) or Lewy body disorders (LBDs), both diagnoses posed on
      pure clinical grounds, remains quite elusive in term of biomarkers or
      neuropsychological assessment. Whether PD with dementia (PDD) and dementia with
      Lewy bodies (DLB) represent further steps along with a continuum of the same
      progressive degeneration due to Lewy bodies deposition, rather then the
      association of Lewy bodies and Abeta pathology, remains a challenging issue. Aim
      of this work is to set a state-of-the-art on the neuropsychological profiles of
      both or DLB. Then, we will focus on the ongoing controversies about the
      specificity of the standard CSF biomarkers if applied to extrapyramidal
      disorders. Our conclusions are that the CSF pattern, in PDD and DLB, can
      certainly be distinct from that in AD, though mechanisms leading to dementia
      could be shared among them. It is possible that, by combining imaging tracers,
      neuropsychologically careful assessment and renewed CSF biomarkers, DLB can be
      better distinguished in subgroups, depending on the presence or absence of a
      relevant amyloid burden. However, more complete data, possibly collected in fieri
      during the progressive derangement of cognitive abilities, are needed to improve
      our ability to decipher and treat these entities.

PMID- 22622366
TI  - A novel ARC gene polymorphism is associated with reduced risk of Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disease, and is
      clinically characterized by cognitive disturbances and the accumulation of the
      amyloid beta (Abeta) peptides in plaques in the brain. Recent studies have shown
      the links between AD and the immediate-early gene Arc (activity-regulated
      cytoskeleton-associated protein), involved in synaptic plasticity and memory
      consolidation. For example, AD mouse models show a decreased expression of Arc
      mRNA in the brain. In additional, acute Abeta application to brain slices leads
      to a widespread ARC protein diffusion, unlike the normal defined localization to
      synapses. In this study, we investigated genetic variation in human ARC and the
      risk of developing AD. To this end, we genotyped 713 subjects diagnosed with AD
      and 841 controls without dementia. ARC was sequenced in a group of healthy
      individuals, and seven previously known SNPs and three novel SNPs were
      identified. Two of the newly found SNPs were intronic and one, +2852(G/A), was
      located in the 3'UTR. Three tag SNPs were selected, including the novel SNP
      +2852(G/A), to relate to risk of AD, Mini Mental State Examination (MMSE) scores
      and cerebrospinal fluid (CSF) biomarker levels of total tau (T-tau),
      hyperphosphorylated tau181 (P-tau(181)) and Abeta(1-42). The AA genotype of the
      newly found 3'-UTR SNP +2852(A/G), was associated with a decreased risk of AD (p
      (c) = 0.005; OR = 0.74; 95 % CI: 0.61-0.89). No associations of single SNPs or
      haplotypes with MMSE score or CSF biomarkers were found. Here we report a novel
      ARC SNP associated with a reduced risk of developing AD. To our knowledge, this
      is the first study associating a gene variant of ARC with any disease. The
      location of the SNP within the 3'UTR indicates that dendritic targeting of ARC
      mRNA could be involved in the molecular mechanisms underlying this protective
      function. However, further investigation of the importance of this SNP for ARC
      function, ARC processing and the pathology of AD is needed.

PMID- 22622367
TI  - Extracts of Sideritis scardica as triple monoamine reuptake inhibitors.
AB  - Sideritis species are traditionally used within the Mediterranean area as teas,
      flavouring agents or for therapeutical purposes. The aim of this study was to
      investigate the effects of Sideritis scardica extracts on the monoamine
      transporters and to derive and explain possible medicinal applications from the
      pharmacological profile of the extracts. We have studied the effect of various S.
      scardica extracts on serotonin, noradrenaline and dopamine uptake in rat brain
      synaptosomes and serotonin uptake in human JAR cells. All extracts inhibited the
      uptake of all three monoamines into rat brain synaptosomes by their respective
      transporters, the alcoholic extracts being more effective than the water extract.
      EC(50) values were in the range of 30-40 MUg/ml. Inhibition of the human
      serotonin transporter by the methanol extract was even more effective (EC(50) 1.4
      MUg/ml). Combining Sideritis ethanol extract and fluvoxamine resulted in a
      leftward shift of the fluvoxamine concentration-response curve. The
      pharmacological profile of S. scardica extracts as triple monoamine reuptake
      inhibitors suggests their use in the phytochemical therapy of mental disorders
      associated with a malfunctioning monoaminergic neurotransmission, such as anxiety
      disorders, major depression, attention-deficit hyperactivity disorder, mental
      impairment or neurodegenerative diseases.

PMID- 22622368
TI  - Indicators for elevated risk factors for alcohol-withdrawal seizures: an analysis
      using a random forest algorithm.
AB  - Alcohol-withdrawal seizures (AWS) are an important and relevant complication
      during detoxification in alcohol-dependent patients. Therefore, it is important
      to evaluate the individual risk for AWS. We apply a random forest algorithm to
      assess possible predictive markers in a large sample of 200 alcohol-dependent
      patients undergoing alcohol withdrawal. This analysis showed that the combination
      of homocysteine, prolactin, blood alcohol concentration on admission, number of
      preceding withdrawals, age and the number of cigarettes smoked may successfully
      predict AWS. In conclusion, the results of this analysis allow for origination of
      further research, which should include additional biological and psychosocial
      parameters as well as consumption behaviour.

PMID- 22622369
TI  - Increased concentration of the CSF Tau protein and its phosphorylated form in the
      late juvenile metachromatic leukodystrophy form: a case report.
AB  - Metachromatic leukodystrophy (MLD) is an autosomal recessive, lysosomal storage
      disease due to deficiency or absence of arylsulfatase A enzyme (ASA) with
      sulfatide accumulation in the central and peripheral nervous system, kidneys, and
      gallbladder, leading to many dysfunctions. One of the clinical forms of the
      disease is a late juvenile MLD. To our best knowledge, this is the first report
      describing increased Tau/pTau and normal Abeta1-42 concentrations in the CSF of
      the late juvenile MLD patient.

PMID- 22622370
TI  - Effects of alfuzosin with methylprednisolone for spontaneous expulsion and pain
      control of lower ureteral stone.
AB  - The aim of this study is to evaluate the efficacy of alfuzosin with
      methylprednisolone on expulsion and pain control of lower ureteral stones <10 mm
      in size. Between June 2005 and June 2007, 113 patients with lower ureteral stones
      <10 mm in size were enrolled in the study. The patients were divided into a
      control group (group I) and medical expulsive therapy group (group II). Group I
      (n = 66) received oral analgesics daily and group II (n = 47) received the same
      analgesics along with 10 mg alfuzosin and 8 mg methylprednisolone for 4 weeks
      orally once a day. The treatment was continued until stone expulsion or to a
      maximum of 4 weeks. All patients were allowed 25 mg pethidine hydrochloride
      intramuscular injections if needed for suboptimal pain control. The average stone
      size was 6.15 mm in group I and 5.42 mm in group II. Of the 113 patients, 80
      became stone free (70.7%). Group II had significantly higher stone free rates
      (82.9 vs. 62.1%, p = 0.014), fewer expulsion times (mean 4.4 vs. 7.3 days, p =
      0.001), and mean number of intramuscular analgesic injections (0.8 vs. 2.1)
      compared to group I. Alfuzosin with methylprednisolone treatment seems safe and
      effective for lower ureteral stones <10 mm in size as demonstrated by the
      increased stone free rate, earlier expulsion, and reduced additional analgesic
      therapy.

PMID- 22622371
TI  - Studies on the in vitro and in vivo antiurolithic activity of Holarrhena
      antidysenterica.
AB  - Holarrhena antidysenterica has a traditional use in the treatment of
      urolithiasis, therefore, its crude extract has been investigated for possible
      antiurolithic effect. The crude aqueous-methanolic extract of Holarrhena
      antidysenterica (Ha.Cr) was studied using the in vitro and in vivo methods. In
      the in vitro experiments, Ha.Cr demonstrated a concentration-dependent (0.25-4
      mg/ml) inhibitory effect on the slope of aggregation. It decreased the size of
      crystals and transformed the calcium oxalate monohydrate (COM) to calcium oxalate
      dehydrate (COD) crystals, in calcium oxalate metastable solutions. It also showed
      concentration-dependent antioxidant effect against 2,2-diphenyl-1-picrylhydrazyl
      (DPPH) free radicals and lipid peroxidation induced in rat kidney tissue
      homogenate. Ha.Cr (0.3 mg/ml) reduced (p < 0.05) the cell toxicity and LDH
      release in renal epithelial cells (MDCK) exposed to oxalate (0.5 mM) and COM (66
      MUg/cm(2)) crystals. In male Wistar rats, receiving 0.75 % ethylene glycol (EG)
      for 21 days along with 1 % ammonium chloride (AC) in drinking water, Ha.Cr
      treatment (30-100 mg/kg) prevented the toxic changes caused by lithogenic agents;
      EG and AC, like loss of body weight, polyurea, oxaluria, raised serum urea and
      creatinine levels and crystal deposition in kidneys compared to their respective
      controls. These data indicate that Holarrhena antidysenterica possesses
      antiurolithic activity, possibly mediated through the inhibition of CaOx crystal
      aggregation, antioxidant and renal epithelial cell protective activities and may
      provide base for designing future studies to establish its efficacy and safety
      for clinical use.

PMID- 22622372
TI  - Radiationless deactivation of 6-aminocoumarin from the S1-ICT state in
      nonspecifically interacting solvents.
AB  - This paper presents the results of a spectral (absorption and emission) and
      photophysical study of 6-aminocoumarin (6AC) in the solvents with which this
      molecule interacts only nonspecifically (n-alkanes, tetrachloromethane and 1
      chloro-n-alkanes) and in nitriles. The strong effects of the solvents on the
      emission spectra, fluorescence quantum yield and lifetime of 6AC were observed.
      The results of the steady-state and time-resolved photophysical study suggest the
      presence of very fast nonradiative deactivation processes. It is concluded that
      besides fluorescence, the efficient S(1)-ICT -> S(0) internal conversion in
      nonpolar aprotic solvents arises from vibronic interactions between close-lying
      S(1)-ICT(pi,pi*) and S(2)(n,pi*) states. Moreover, unexpectedly efficient triplet
      state formation occurs. In nitriles the intermolecular hydrogen-bonding
      interactions with solvent molecules also facilitate the nonradiative decay
      process involving the S(1)-exciplex.

PMID- 22622373
TI  - Invited commentary on Hayes et al.

PMID- 22622383
TI  - No effect of scapular position on 3-dimensional scapular motion in the throwing
      shoulder of healthy professional pitchers.
AB  - CONTEXT: Differences in 3-dimensional (3D) scapular motion have been reported
      between healthy baseball position players and healthy nonoverhead athletic
      controls, as well as players diagnosed with shoulder impingement syndrome. These
      alterations are theorized to be the result of adaptations due to the demands of
      repetitive throwing. However, comparisons between the throwing and nonthrowing
      shoulders are commonly used to infer normal motion. OBJECTIVE: The purpose of
      this study was to compare 3D scapular kinematics between the throwing and
      nonthrowing shoulders in asymptomatic professional male baseball pitchers.
      DESIGN: Cross-sectional study. SETTING: Laboratory. PARTICIPANTS: 45 asymptomatic
      professional baseball pitchers participating without restrictions during
      preseason training. INTERVENTIONS: An electromagnetic tracking system was used to
      assess 3D scapular orientation at rest and during weighted (2.3-kg) shoulder
      flexion across discrete humeral-flexion angles (rest, 30 degrees , 60 degrees ,
      90 degrees , 120 degrees , and maximum). MAIN OUTCOME MEASURE: 3D scapular
      upward/downward rotation (UR/DR), anteroposterior (AP) tilt, and
      internal/external rotation (IR/ER). Separate mixed-model ANOVAs (Side * Angle)
      for each scapular motion were used to compare the throwing and the nonthrowing
      shoulder across all angles. RESULTS: There were significant side-to-side
      differences with scapular UR/DR (P < .001), AP tilt (P < .001), and IR/ER (P <
      .001). The throwing scapula displayed greater mean UR (increase = 3.6 degrees ,
      SE = 0.50) and anterior/posterior tilt (increase = 2.1 degrees , SE = 0.60) and
      less mean IR (decrease = 2.1 degrees , SE = 0.66) than the nonthrowing shoulder
      averaged across all arm angles. CONCLUSIONS: In asymptomatic professional
      pitchers, the throwing shoulder's scapular position differs across all arm angles
      from that of the nonthrowing shoulder, but the motion does not differ. Scapular
      asymmetry that is consistent throughout arm elevation may be indicative not of
      pathology but, potentially, of a normal adaptation of the pitching shoulder.

PMID- 22622384
TI  - The effect of muscle energy techniques on disability and pain scores in
      individuals with low back pain.
AB  - CLINICAL SCENARIO: Low back pain is the most common type of pain reported by
      adults in the United States. A variety of manual therapy techniques are used in
      the management of low back pain to reduce pain, improve function, and reduce
      disability. In recent years, muscle energy techniques have been increasingly used
      in clinics to treat low back pain. By definition, a muscle energy technique
      involves the patient performing a voluntary muscle contraction "in a precisely
      controlled direction, against a distinctly executed counter force applied by the
      operator." Muscle energy techniques provide a conservative alternative for
      clinicians treating patients with precautions or contraindications to joint
      manipulation.

PMID- 22622385
TI  - Effectiveness of external-rotation immobilization after initial shoulder
      dislocation in reducing recurrence rates.
AB  - CLINICAL SCENARIO: Initial, traumatic shoulder dislocations, particularly in an
      anterior direction, are among the most common shoulder injuries. Traditionally,
      nonsurgical treatment for first-time shoulder dislocations consists of
      immobilization in internal rotation (IR). However, there is a high rate of
      recurrence after this course of treatment. Recent reports indicate that
      immobilization in external rotation (ER) instead of IR may more effectively
      reduce recurrence rates, resulting in a viable nonsurgical treatment option for
      patients sustaining an initial shoulder dislocation.

PMID- 22622388
TI  - Synthesis of peptidomimetics, delta- and epsilon-lactam tetrazoles.
AB  - A concise two-step procedure for the synthesis of novel delta-lactam tetrazoles
      has been established via the Ugi-azide reaction using 5-oxohexanoic acid along
      with primary amines, isocyanides, and azidotrimethylsilane followed by 1,1'
      carbonyldiimidazole-mediated intramolecular amide formation. Expansion to epsilon
      lactam tetrazole scaffolds was accomplished using methyl 6-oxoheptanoate via the
      same Ugi-azide reaction followed by basic hydrolysis and SOCl(2) activation to
      enable lactam formation.

PMID- 22622389
TI  - Applications of ortho-phenylisonitrile and ortho-N-Boc aniline for the two-step
      preparation of novel bis-heterocyclic chemotypes.
AB  - Concise routes to five pharmacologically relevant bis-heterocyclic scaffolds are
      described. Significant molecular complexity is generated in a mere two synthetic
      operations enabling access to each scaffold. Routes are often improved by
      microwave irradiation and all utilize isocyanide-based multi-component reaction
      methods to incorporate the required diversity elements. Common reagents in all
      initial condensation reactions include 2-(N-Boc-amino)-phenyl-isocyanide 1, mono
      Boc-phenylenediamine 2 and ethyl glyoxalate 3.

PMID- 22622390
TI  - Electron-poor N-substituted imide-fused corannulenes.
AB  - N-Substituted imide-fused corannulenes can be generated from the corresponding
      tetramethylfluoranthenes. Syntheses, crystal structure and electronic properties
      are reported. The solid state structure of the pentafluorophenyl derivative shows
      nearly perfect pi-stacking in a convex-concave fashion and is expected to possess
      useful electronic properties.

PMID- 22622391
TI  - Cost-effectiveness analysis of the neuroprotective agent edaravone for
      noncardioembolic cerebral infarction.
AB  - BACKGROUND: The free radical scavenger edaravone has been reported useful for
      improvement in activities of daily living and for prevention of recurrent stroke
      in the edaravone versus sodium ozagrel in acute noncardioembolic ischemic stroke
      (EDO) trial. The aim of this report was to evaluate the cost-effectiveness of
      edaravone compared to the intravenous antiplatelet drug ozagrel sodium (ozagrel)
      for noncardioembolic stroke (non-CES) based on the EDO trial data. METHODS: A
      cost-effectiveness analysis was performed using the Markov model, which also
      incorporated the long-term course after the acute stage of non-CES. From the
      perspective of a health care payer, direct medical costs and nursing care costs
      were taken into account in the cost analysis. The quality-adjusted life year
      (QALY) served as an indicator of effectiveness. Simulation at 5 and 10 years
      after the onset of non-CES was carried out. The study involved 68-year-old
      patients with non-CES, selected against the EDO trial subject selection criteria.
      A 14-day treatment with edaravone 60 mg/day or ozagrel 160 mg/day was assumed as
      acute treatment for non-CES. RESULTS: The use of edaravone was associated with a
      reduction in total costs (0.51 million yen [$6,374] at 5 years and 0.64 million
      yen [$8,039]) at 10 years after the onset of non-CES) and improvement in QALYs
      (0.23 at 5 years and 0.38 at 10 years). Compared to ozagrel therapy, edaravone
      therapy was a cost-saving strategy for treating non-CES. CONCLUSIONS: Compared to
      ozagrel therapy, edaravone therapy for non-CES is not only useful from a clinical
      viewpoint, but also valuable from a socioeconomic perspective.

PMID- 22622393
TI  - Formic acid electro-synthesis from carbon dioxide in a room temperature ionic
      liquid.
AB  - The novel synthesis of formic acid has been achieved in a room temperature ionic
      liquid via the reaction of electro-activated carbon dioxide and protons on pre
      anodised platinum. Only mild reaction conditions of room temperature and 1 atm
      CO(2) were used. This work highlights the effect of pre-anodisation on Pt
      surfaces.

PMID- 22622392
TI  - Is genotypic variation of H+ efflux under P deficiency linked with nodulated-root
      respiration of N2 fixing common-bean (Phaseolus vulgaris L.)?
AB  - To examine genotypic variation of common bean in growth, phosphorus uptake,
      nodulated-root proton release, and nodule gas permeability, seven common bean
      recombinant inbred lines (RIL) from the cross of BAT477*DOR364 were inoculated by
      Rhizobium tropici CIAT 899 and grown in hydroaeroponic culture under glasshouse
      conditions. A positive correlation was observed between shoot and nodule biomass
      for most of the studied RILs. Under P deficiency, the tolerant common bean RILs
      acidified more of their rhizosphere than the sensitive ones. The proton release
      of the RILs 147, 124, 104, 75 and RIL34 was positively correlated with nodule O2
      permeability. We conclude that nodulated common bean plants release a substantial
      amount of H+ into the rhizosphere that is linked to the symbiotic N2 fixation. It
      depends upon the nodule permeability to O2 diffusion, and varies with genotype.

PMID- 22622394
TI  - Trends and variations in utilization of nephron-sparing procedures for stage I
      kidney cancer in the United States.
AB  - PURPOSE: The incidental detection of early-stage kidney tumors is increasing in
      the United States. Nephron-sparing approaches (NS) to managing these tumors are
      equivalent to radical nephrectomy (RN) in oncologic outcomes and have a decreased
      impact on renal function. Our objective was to evaluate trends in the use of NS
      over the past decade and the socioeconomic factors associated with its use.
      METHODS: The National Cancer Database was queried to identify patients with stage
      I kidney cancer between 2000 and 2008. Patients were classified by the type of
      surgery as NS (local destruction and local excision) or RN. Patients were further
      categorized by age, race, insurance status, and income. Log-binomial regression
      was used to estimate prevalence ratios (PR) for the proportion of NS to RN
      according to demographic and socioeconomic characteristics. RESULTS: From 2000 to
      2008, there were 142,194 cases of kidney cancer reported to the NCDB. In these
      cases, 43,034 (30.3 %) patients had NS, and 86,431 (60.78 %) patients had RN. The
      prevalence of NS increased 10 % per year (PR = 1.10, p < 0.0001)-from 20.0 % in
      2000 to 45.1 % in 2008. Older age, lower income, Black race, Hispanic ethnicity,
      and lack of health insurance were associated with a decreased prevalence of NS.
      CONCLUSIONS: NS as a treatment for stage I kidney cancer has increased steadily
      since 2000. Age, racial, and socioeconomic differences may exist in the
      utilization of NS. Additional analyses, with patient level data, are required to
      address the independent significance of these variables in an effort to develop
      strategies to mitigate these potential disparities.

PMID- 22622395
TI  - Comparison of renal function and metabolic abnormalities of cystine stone
      patients and calcium oxalate stone patients in China.
AB  - PURPOSE: To compare renal function and metabolic abnormalities of cystine stone
      patients and calcium oxalate stone patients in China. METHODS: Between 2008 and
      2011, thirty cystine stone patients were involved in our study, and an equal
      number of age- and gender pair-matched patients with calcium oxalate stones. Non
      stone forming individuals were elected as controls. The evaluation included blood
      chemistry studies and 24-h urine collection in both groups of patients. RESULTS:
      The cystine stone patients had higher mean values of serum blood urea nitrogen,
      urate and creatinine levels than patients in other two groups. With respect to
      urine risk factors, cystine stone patients had higher urinary citrate and lower
      urinary oxalate and creatinine than calcium oxalate stone patients. When compared
      to non-stone forming individuals, cystine stone patients had higher urinary urate
      excretion and lower urinary creatinine excretion. Metabolic abnormalities could
      be demonstrated in 80 % of the cystine stone patients and in 100 % of the calcium
      oxalate stone patients. We also compared urine risk factors among cystine stone
      patients with different urine cystine excretion (<1 mmol/24 h, 1-2 mmol/24 h and
      >2 mmol/24 h). No significant difference was found in urine risk factors among
      three groups. CONCLUSIONS: This study suggested that cystine stone patients were
      at greater risk for the loss of renal function than calcium oxalate stone
      patients, but the risk of the formation of calcium oxalate stones was lower. Our
      results also indicated that urinary cystine had little or no impact on the
      excretion of urine chemistries in cystine stone patients.

PMID- 22622396
TI  - Transcutaneous electrical nerve stimulation: an effective treatment for
      refractory non-neurogenic overactive bladder syndrome?
AB  - PURPOSE: To assess the effect of transcutaneous electrical nerve stimulation
      (TENS) for treating refractory overactive bladder syndrome (OAB). PATIENTS AND
      METHODS: A consecutive series of 42 patients treated with TENS for refractory OAB
      was prospectively investigated at an academic tertiary referral centre. Effects
      were evaluated using bladder diary for at least 48 h and satisfaction assessment
      at baseline, after 12 weeks of TENS treatment, and at the last known follow-up.
      Adverse events related to TENS were also assessed. RESULTS: Mean age of the 42
      patients (25 women, 17 men) was 48 years (range, 18-76). TENS was successful
      following 12 weeks of treatment in 21 (50 %) patients, and the positive effect
      was sustained during a mean follow-up of 21 months (range, 6-83 months) in 18
      patients. Following 12 weeks of TENS treatment, mean number of voids per 24 h
      decreased significantly from 15 to 11 (p < 0.001) and mean voided volume
      increased significantly from 160 to 230 mL (p < 0.001). In addition, TENS
      completely restored continence in 7 (39 %) of the 18 incontinent patients. Before
      TENS, all 42 patients were dissatisfied or very dissatisfied; following 12 weeks
      of TENS treatment, 21 (50 %) patients felt satisfied or very satisfied (p <
      0.001). No adverse events related to TENS were noted. CONCLUSIONS: TENS seems to
      be an effective and safe treatment for refractory OAB warranting randomized,
      placebo-controlled trials.

PMID- 22622397
TI  - Effect of selective inhibition of renal inducible nitric oxide synthase on renal
      blood flow and function in experimental hyperdynamic sepsis.
AB  - OBJECTIVE: Nitric oxide plays an important role in the control of renal blood
      flow and renal function. In sepsis, increased levels of inducible nitric oxide
      synthase produce excessive nitric oxide, which may contribute to the development
      of acute kidney injury. We, therefore, examined the effects of intrarenal
      infusion of selective inducible nitric oxide synthase inhibitors in a large
      animal model of hyperdynamic sepsis in which acute kidney injury occurs in the
      presence of increased renal blood flow. DESIGN: Prospective crossover randomized
      controlled interventional studies. SETTING: University-affiliated research
      institute. SUBJECTS: Twelve unilaterally nephrectomized Merino ewes.
      INTERVENTION: Infusion of a selective (1400W) and a partially selective inducible
      nitric oxide synthase inhibitor (aminoguanidine) into the renal artery for 2 hrs
      after the induction of sepsis, and comparison with a nonselective inhibitor
      (Nomega-nitro-L-arginine methyl ester). MEASUREMENTS AND MAIN RESULTS: In sheep
      with nonhypotensive hyperdynamic sepsis, creatinine clearance halved (32 to 16
      mL/min, ratio [95% confidence interval] 0.51 [0.28-0.92]) despite increased renal
      blood flow (241 to 343 mL/min, difference [95% confidence interval] 102 [78
      126]). Infusion of 1400W did not change renal blood flow, urine output, or
      creatinine clearance, whereas infusion of Nomega-nitro-L-arginine methyl ester
      and a high dose of aminoguanidine normalized renal blood flow, but did not alter
      creatinine clearance. CONCLUSIONS: In hyperdynamic sepsis, intrarenal infusion of
      a highly selective inducible nitric oxide synthase inhibitor did not reduce the
      elevated renal blood flow or improve renal function. In contrast, renal blood
      flow was reduced by infusion of a nonselective NOS inhibitor or a high dose of a
      partially selective inducible nitric oxide synthase inhibitor. The renal
      vasodilatation in septic acute kidney injury may be due to nitric oxide derived
      from the endothelial and neural isoforms of nitric oxide synthase, but their
      blockade did not restore renal function.

PMID- 22622398
TI  - Continuous determination of optimal cerebral perfusion pressure in traumatic
      brain injury.
AB  - OBJECTIVES: We have sought to develop an automated methodology for the continuous
      updating of optimal cerebral perfusion pressure (CPPopt) for patients after
      severe traumatic head injury, using continuous monitoring of cerebrovascular
      pressure reactivity. We then validated the CPPopt algorithm by determining the
      association between outcome and the deviation of actual CPP from CPPopt. DESIGN:
      Retrospective analysis of prospectively collected data. SETTING: Neurosciences
      critical care unit of a university hospital. PATIENTS: A total of 327 traumatic
      head-injury patients admitted between 2003 and 2009 with continuous monitoring of
      arterial blood pressure and intracranial pressure. MEASUREMENTS AND MAIN RESULTS:
      Arterial blood pressure, intracranial pressure, and CPP were continuously
      recorded, and pressure reactivity index was calculated online. Outcome was
      assessed at 6 months. An automated curve fitting method was applied to determine
      CPP at the minimum value for pressure reactivity index (CPPopt). A time trend of
      CPPopt was created using a moving 4-hr window, updated every minute.
      Identification of CPPopt was, on average, feasible during 55% of the whole
      recording period. Patient outcome correlated with the continuously updated
      difference between median CPP and CPPopt (chi-square=45, p<.001; outcome
      dichotomized into fatal and nonfatal). Mortality was associated with relative
      "hypoperfusion" (CPP<CPPopt), severe disability with "hyperperfusion"
      (CPP>CPPopt), and favorable outcome was associated with smaller deviations of CPP
      from the individualized CPPopt. While deviations from global target CPP values of
      60 mm Hg and 70 mm Hg were also related to outcome, these relationships were less
      robust. CONCLUSIONS: Real-time CPPopt could be identified during the recording
      time of majority of the patients. Patients with a median CPP close to CPPopt were
      more likely to have a favorable outcome than those in whom median CPP was widely
      different from CPPopt. Deviations from individualized CPPopt were more predictive
      of outcome than deviations from a common target CPP. CPP management to optimize
      cerebrovascular pressure reactivity should be the subject of future clinical
      trial in severe traumatic head-injury patients.

PMID- 22622400
TI  - Patient-centered critical care reconsidered: ruminations on bygone continuity and
      fear and trembling.

PMID- 22622399
TI  - Effects of exogenous ubiquitin in a polytrauma model with blunt chest trauma.
AB  - OBJECTIVE: To determine whether treatment with the CXC chemokine receptor 4
      agonist ubiquitin results in beneficial effects in a polytrauma model consisting
      of bilateral femur fractures plus blunt chest trauma (Injury Severity Score 18
      25). DESIGN: Treatment study. SETTING: Research laboratory. SUBJECTS: Seventeen
      Yorkshire pigs. INTERVENTIONS: Intravenous injection of 1.5 mg/kg ubiquitin or
      albumin (control) at 60 mins after polytrauma. MEASUREMENTS AND MAIN RESULTS:
      Anesthetized, mechanically ventilated pigs underwent polytrauma, followed by a
      simulated 60-min shock phase. At the end of the shock phase, ubiquitin or albumin
      were administered and animals were resuscitated to a mean arterial blood pressure
      of 70 mm Hg until t=420 mins. After intravenous ubiquitin, ubiquitin plasma
      concentrations increased 16-fold to 2870+/-1015 ng/mL at t=90 mins and decreased
      with t1/2=60 mins. Endogenous plasma ubiquitin increased two-fold in the albumin
      group with peak levels of 359+/-210 ng/mL. Plasma levels of the cognate CXC
      chemokine receptor 4 ligand stromal cell-derived factor-1alpha were unchanged in
      both groups. Ubiquitin treatment reduced arterial lactate levels and prevented a
      continuous decrease in arterial oxygenation, which occurred in the albumin group
      during resuscitation. Wet weight to dry weight ratios of the lung contralateral
      from the injury, heart, spleen and jejunum were lower with ubiquitin. With
      ubiquitin treatment, tissue levels of Interleukin-8, Interleukin-10, Tumor
      Necrosis Factor alpha, and stromal cell-derived factor-1alpha were reduced in the
      injured lung and of Interleukin-8 in the contralateral lung, respectively.
      CONCLUSIONS: Administration of exogenous ubiquitin modulates the local
      inflammatory response, improves resuscitation, reduces fluid shifts into tissues,
      and preserves arterial oxygenation after blunt polytrauma with lung injury. This
      study further supports the notion that ubiquitin is a promising protein
      therapeutic and implies CXC chemokine receptor 4 as a drug target after
      polytrauma.

PMID- 22622401
TI  - Comparison of two guideline-concordant antimicrobial combinations in elderly
      patients hospitalized with severe community-acquired pneumonia.
AB  - OBJECTIVE: Two of the guideline-concordant therapies for severe community
      acquired pneumonia are either a beta-lactam and fluoroquinolone or beta-lactam
      and macrolide. However it is unclear if there is a benefit for one vs. the other
      for elderly patients with severe community-acquired pneumonia. DESIGN: A
      retrospective population-based cohort study of patients with community-acquired
      pneumonia. SETTING: Patients admitted to an intensive care unit of any Department
      of Veterans Affairs hospital during 5-yr period. PATIENTS: We included only those
      patients>65 yrs of age admitted to the intensive care unit with community
      acquired pneumonia who received either beta-lactam+fluoroquinolone or beta
      lactam+macrolide antibiotic therapy for pneumonia. INTERVENTION: Not applicable.
      MEASUREMENTS: We used multilevel regression models to examine the effect of beta
      lactam+fluoroquinolone vs. beta-lactam+macrolide on each of the outcomes after
      adjusting for potential confounders using propensity scores. MAIN RESULTS: The
      cohort consisted of 1,989 patients: 98.5% male and a mean age of 74 yrs. For
      treatment, 44% of subjects received beta-lactam+fluoroquinolone and 56% received
      beta-lactam+macrolide. Unadjusted 30-day mortality was 27% for beta
      lactam+fluoroquinolone and 24% for beta-lactam+macrolide (p=.11). In the
      multilevel models, the use of beta-lactam+fluoroquinolone was not significantly
      associated with 30-day mortality (odds ratio 1.05, 95% confidence interval 0.85
      1.30). However, the use of beta-lactam+fluoroquinolone was significantly
      associated with increased mean length of stay (incidence rate ratio 1.30, 95%
      confidence interval 1.27-1.33). CONCLUSIONS: We found no significant difference
      for 30-day mortality but did demonstrate an association with increase in length
      of stay associated with the use of beta-lactam + fluoroquinolone. Randomized
      controlled trials are needed to determine the most effective antibiotics regimes
      for patients with severe pneumonia.

PMID- 22622402
TI  - Linezolid limits burden of methicillin-resistant Staphylococcus aureus in biofilm
      of tracheal tubes.
AB  - OBJECTIVE: To evaluate the effects of systemic treatment with linezolid compared
      with vancomycin on biofilm formation in mechanically ventilated pigs with severe
      methicillin-resistant Staphylococcus aureus-induced pneumonia. DESIGN:
      Prospective randomized animal study. SETTING: Departments of Pneumology,
      Microbiology, and Pharmacy of the Hospital Clinic, Barcelona, and Scientific and
      Technological Services of the University of Barcelona. SUBJECTS: We prospectively
      analyzed 70 endotracheal tube samples. Endotracheal tubes were obtained from pigs
      either untreated (controls, n=20), or treated with vancomycin (n=32) or linezolid
      (n=18). INTERVENTIONS: The endotracheal tubes were obtained from a previous
      randomized study in tracheally intubated pigs with methicillin-resistant
      Staphylococcus aureus severe pneumonia, and mechanically ventilated for 69+/-16
      hrs. MEASUREMENTS AND MAIN RESULTS: Distal and medial hemisections of the
      endotracheal tube were assessed to quantify methicillin-resistant Staphylococcus
      aureus burden, antibiotic biofilm concentration by high-performance liquid
      chromatography or bioassay, and biofilm thickness through scanning electron
      microscopy. We found a trend toward a significant variation in biofilm
      methicillin-resistant Staphylococcus aureus burden (log colony-forming unit/mL)
      among groups (p=.057), and the lowest bacterial burden was found in endotracheal
      tubes treated with linezolid (1.98+/-1.68) in comparison with untreated
      endotracheal tubes (3.72+/-2.20, p=.045) or those treated with vancomycin (2.97+/
      2.43, p=.286). Biofilm linezolid concentration was 19-fold above the linezolid
      minimum inhibitory concentration, whereas biofilm vancomycin concentration
      (1.60+/-0.91 ug/mL) was consistently below or close to the vancomycin minimum
      inhibitory concentration. Biofilm was thicker in the vancomycin group (p=.077).
      CONCLUSIONS: Systemic treatment with linezolid limits endotracheal tube biofilm
      development and methicillin-resistant Staphylococcus aureus burden. The potential
      clinical usefulness of linezolid in decreasing the risk of biofilm-related
      respiratory infections during prolonged tracheal intubation requires further
      investigation.

PMID- 22622403
TI  - Mild therapeutic hypothermia improves outcomes compared with normothermia in
      cardiac-arrest patients--a retrospective chart review.
AB  - OBJECTIVE: Studies showing the effectiveness of therapeutic hypothermia (32-34
      degrees C) in postcardiac arrest patients have been criticized because of
      patients with elevated body temperature (>37.5 degrees C) in the noncooled
      control group. Thus, the effects of spontaneous normothermia (<37.5 degrees C)
      compared with mild therapeutic hypothermia were studied. DESIGN: Retrospective
      chart review from 1991 to 2010. PATIENTS: Witnessed out-of-hospital arrest,
      presumed to be of cardiac origin, aged 18 to 80 yrs and with a Glassgow Coma
      Scale score of <8 at admission. INTERVENTIONS: Patients with sustained
      restoration of spontaneous circulation who did not receive therapeutic
      hypothermia and never exceeded 37.5 degrees C during the 36 hrs postcardiac
      arrest were compared with patients who received mild therapeutic hypothermia.
      MEASUREMENTS AND MAIN RESULTS: The primary end point was a favorable neurological
      outcome, defined as Cerebral Performance Categories 1 or 2; the secondary end
      point was overall survival to 180 days. Significantly more patients in the
      hypothermia group had Cerebral Performance Categories 1 or 2 (hypothermia: 256 of
      467 [55%] vs. normothermia: 69 of 165 [42%]) and survived for >180 days
      (hypothermia: 315 of 467 [67%] vs. normothermia: 79 of 165 [48%]). The propensity
      score adjusted risk ratio for good neurological outcome of patients undergoing
      hypothermia treatment was 1.37 (confidence interval 1.09-1.72, p<=.01) and for
      dying within 180 days was 0.57 (confidence interval 0.44-0.73, p<=.01) compared
      to normothermia. CONCLUSIONS: Therapeutic hypothermia is associated with
      significantly improved neurological outcome and 180-day survival compared to
      spontaneous normothermia in cardiac-arrest patients.

PMID- 22622404
TI  - Effects of a diabetes-specific enteral nutrition on nutritional and immune status
      of diabetic, obese, and endotoxemic rats: interest of a graded arginine supply.
AB  - OBJECTIVE: Obese and type 2 diabetic patients present metabolic disturbance
      related alterations in nonspecific immunity, to which the decrease in their
      plasma arginine contributes. Although diabetes-specific formulas have been
      developed, they have never been tested in the context of an acute infectious
      situation as can be seen in intensive care unit patients. Our aim was to
      investigate the effects of a diabetes-specific diet enriched or not with arginine
      in a model of infectious stress in a diabetes and obesity situation. As a large
      intake of arginine may be deleterious, this amino acid was given in graded
      fashion. DESIGN: Randomized, controlled experimental study. SETTING: University
      research laboratory. SUBJECTS: Zucker diabetic fatty rats. INTERVENTIONS:
      Gastrostomized Zucker diabetic fatty rats were submitted to intraperitoneal
      lipopolysaccharide administration and fed for 7 days with either a diabetes
      specific enteral nutrition without (G group, n=7) or with graded arginine supply
      (1-5 g/kg/day) (GA group, n=7) or a standard enteral nutrition (HP group, n=10).
      MEASUREMENTS AND MAIN RESULTS: Survival rate was better in G and GA groups than
      in the HP group. On day 7, plasma insulin to glucose ratio tended to be lower in
      the same G and GA groups. Macrophage tumor necrosis factor-alpha (G: 5.0+/-1.1
      ng/2*106 cells.hr-1; GA: 3.7+/-0.8 ng/2*106 cells.hr-1; and HP: 1.7+/-0.6
      ng/2*106 cells.hr-1; p<.05 G vs. HP) and nitric oxide (G: 4.5+/-1.1 ng/2*106
      cells.hr-1; GA: 5.1+/-1.0 ng/2*106 cells.hr-1; and HP: 1.0+/-0.5 nmol/2*106
      cells.hr-1; p<.05 G and GA vs. HP) productions were higher in the G and GA groups
      compared to the HP group. Macrophages from the G and GA groups exhibited
      increased arginine consumption. CONCLUSIONS: In diabetic obese and endotoxemic
      rats, a diabetes-specific formula leads to a lower mortality, a decreased insulin
      resistance, and an improvement in peritoneal macrophage function. Arginine
      supplementation has no additional effect. These data support the use of such
      disease-specific diets in critically ill diabetic and obese patients.

PMID- 22622405
TI  - Safety and pharmacokinetics of an anti-PcrV PEGylated monoclonal antibody
      fragment in mechanically ventilated patients colonized with Pseudomonas
      aeruginosa: a randomized,double-blind, placebo-controlled trial.
AB  - OBJECTIVE: The type III secretion system is an important Pseudomonas aeruginosa
      virulence determinant in animal models of infection and in humans. Antibody
      mediated inhibition of the PcrV protein, an essential component of this system,
      might abrogate the Pseudomonas aeruginosa ability to damage epithelial cells,
      neutrophils, and macrophages, thereby limiting its pathogenicity. The objective
      of the trial was to determine the safety, pharmacokinetics, and ability to
      prevent Pseudomonas aeruginosa ventilator-associated pneumonia of KB001, a
      recombinant, PEGylated, engineered, human Fab' fragment that specifically binds
      to a Pseudomonas aeruginosa PcrV epitope and blocks its function. DESIGN:
      Multicenter, randomized, placebo-controlled, double-blind, phase-2a trial.
      SETTING: Ten intensive care units across France. PATIENTS: Thirty-nine
      Pseudomonas aeruginosa-colonized, but not infected, mechanically ventilated
      patients. INTERVENTIONS: Patients were randomized 1:1:1 to receive a single
      intravenous infusion of KB001, 3 mg/kg (n=13) or 10 mg/kg (n=14), or placebo
      (n=12). MEASUREMENTS AND MAIN RESULTS: The primary end points were KB001 safety
      and tolerability, assessed as treatment-related adverse-event frequency and
      severity. Secondary end points included serum and lung KB001 pharmacokinetics,
      and Pseudomonas aeruginosa pneumonia rate within 28 days of its infusion. KB001
      was well tolerated and not immunogenic. The 3- and 10-mg/kg groups had respective
      maximum serum concentrations of 52,811-88,660 and 121,857-285,454 ng/mL, with
      mean elimination half-lives of 8.1 and 9.3 days. KB001 was detected in
      endotracheal aspirates from all patients receiving it, as early as day 1 and up
      to 28 days. Respective mean endotracheal aspirate/serum concentration ratios were
      0.092 and 0.085 for the 3- and 10-mg/kg groups, who developed Pseudomonas
      aeruginosa pneumonia less frequently (33% and 31%, respectively) than placebo
      recipients (60%). CONCLUSIONS: KB001 was safe and well tolerated in this study,
      with a favorable pharmacokinetic profile and promising potential for reducing
      Pseudomonas aeruginosa pneumonia incidence in intensive care unit mechanically
      ventilated patients colonized with this bacterium.

PMID- 22622406
TI  - The detection of EBP50 expression using quantum dot immunohistochemistry in
      pancreatic cancer tissue and down-regulated EBP50 effect on PC-2 cells.
AB  - Ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) is a putative tumor
      suppressor that is correlated with many human cancers. However, the function of
      EBP50 in pancreatic cancer (PC) has not been described. In this paper, the EBP50
      expression level in PC tissues was characterized. In vitro, the effects of EBP50
      down-regulation by siRNA in PC-2 and MiaPaCa-2 cells were evaluated. In addition,
      possible mechanisms that mediate the influence of EBP50 were examined. Our
      results show that the EBP50 expression pattern changes during transformation as
      there is a loss of the normal apical membrane distribution and an ectopic
      cytoplasmic over-expression of EBP50; furthermore, the EBP50 expression level is
      subsequently decreased during malignant progression. Down-regulation of EBP50
      promoted cancer cell proliferation, increased the colony-forming ability of cells
      and accelerated the G1-to-S progression. Additionally, the loss of EBP50
      accentuated beta-catenin activity, increased cyclin E and phosphorylated Rb
      expression, and attenuated p27 expression compared to control cells. Our results
      suggest that EBP50 may function as a potential tumor suppressor.

PMID- 22622407
TI  - Sodium and fluid management in acute brain injury.
AB  - Sodium and fluid management in the brain injured patient directly impacts
      cerebral edema and cerebral perfusion pressure. Sodium is a major determinant of
      neuronal size and therefore hyponatremia is aggressively avoided, as hypoosmolar
      states result in cerebral edema. Negative fluid balance is often avoided because
      resultant drop in cerebral perfusion pressure can contribute to cerebral
      ischemia, further inducing secondary neuronal injury. Patients with brain injury
      are at risk for disorders of sodium and fluid balance (eg, syndrome of
      inappropriate antidiuresis, cerebral salt wasting, and diabetes insipidus).
      Knowledge of normal homeostatic and brain regulatory volume mechanisms is
      necessary to avoid inducing further neuronal or systemic injury while trying to
      correct sodium and fluid disorders in brain injured patients. Osmotherapy is a
      common part of managing cerebral edema in neurocritical care units, but more
      studies are needed to establish practice guidelines.

PMID- 22622408
TI  - Phenotypic differences in Dyt1 between ethnic groups.
AB  - A DYT1 mutation is the most common genetic cause of early-onset primary torsion
      dystonia. Herein we present the phenotypes of 25 Korean dystonia patients with
      DYT1 mutations. We further compare the clinical features of the Asian patients
      with those of the Western DYT 1 mutation patients. In Korean patients, upper
      extremity was the most common site of symptom onset while there were a few
      patients with axial-onset dystonia. Generalized dystonia was the most common
      subtype followed by segmental dystonia. A few patients from the same families had
      their symptoms at the same age. The clinical features of Korean patients were
      similar to those of other Asian patients. The Asian patients were differentiated
      from Western patients by more frequent axial onset, no cranial involvement at
      onset, and more common segmental dystonia. The variable clinical manifestation in
      different ethnic groups may suggest that ethnicity is a significant modifier of
      DYT1 dystonia.

PMID- 22622409
TI  - Epilepsy surgery: still underutilized after all these years.

PMID- 22622411
TI  - Exhaled breath volatile organic compound biomarkers in lung cancer.
AB  - There has been an increased focus on the development of non-invasive biomarkers
      capable of accurately identifying lung cancer early in its course and
      characterizing the nature of the cancer. Exhaled breath is a non-traditional
      source of biomarkers. In the following sections I will outline recent
      developments in the evaluation and management of lung cancer that highlight the
      need for biomarker development, then summarize the evidence suggesting the
      potential of exhaled breath volatile organic compound biomarkers to meet this
      need. I will focus on advances that have taken place since 2008, when this topic
      was last addressed in the Journal of Breath Research.

PMID- 22622410
TI  - Redefining Parkinson's disease research using induced pluripotent stem cells.
AB  - Parkinson's disease (PD) is a movement disorder associated with the degeneration
      of nigral dopaminergic (DA) neurons. One of the greatest obstacles for PD
      research is the lack of patient-specific nigral DA neurons for mechanistic
      studies and drug discovery. The advent of induced pluripotent stem cells (iPSCs)
      has overcome this seemingly intractable problem and changed PD research in many
      profound ways. In this review, we discuss recent development in the generation
      and analyses of patient-specific iPSC-derived midbrain DA neurons. Results from
      this novel platform of human cellular models of PD have offered a tantalizing
      glimpse of the promising future of PD research. With the development of the
      latest genomic modification technologies, dopaminergic neuron differentiation
      methodologies, and cell transplantation studies, PD research is poised to enter a
      new phase that utilizes the human model system to identify the unique
      vulnerabilities of human nigral DA neurons and disease-modifying therapies based
      on such mechanistic studies.

PMID- 22622412
TI  - Low frequency heating of gold nanoparticle dispersions for non-invasive thermal
      therapies.
AB  - Recently gold nanoparticles (GNPs) have been proposed in non-invasive thermal
      therapies for cancer treatment coupled with radiofrequency (RF) waves. In this
      work, the dissipation of RF energy by GNPs is systematically investigated both
      experimentally and theoretically under an EM frequency of 13.56 MHz. To elucidate
      the impurity effect, purified GNP dispersions are obtained through an ultrasonic
      aided method. The result reveals a small bulk temperature increase, i.e., less
      than one centigrade for impurified samples, and even smaller for purified
      samples, which contrasts significantly to some earlier publications. The measured
      dielectric properties of GNP dispersions show a negligible change in the
      effective conductivities for purified samples, which indicates that the
      dielectric loss alone does not predict substantial temperature increase of GNPs.
      Further discussion shows that none of the established theories supports the idea
      that GNPs can dissipate RF energy significantly.

PMID- 22622413
TI  - [CT colonography as routine method].
AB  - CLINICAL/METHODICAL ISSUE: Colorectal cancer is a major public health challenge
      in Austria and Germany. As the participation in dedicated colonoscopy screening
      programs is rather low, the question of alternative methods is raised again and
      computed tomography (CT) colonography seems to be a gentle alternative with a
      very high patient acceptance. STANDARD RADIOLOGICAL METHODS: In recent years CT
      colonography (CTC) has been established besides conventional colonoscopy as a
      radiological method for the investigation of the entire colon. From axial two
      dimensional images three-dimensional images can be generated, allowing a virtual
      flight through the colon which is why this technique is also known as virtual
      colonoscopy. METHODICAL INNOVATIONS: The technique of CTC has been improved
      continuously during recent years. On the one hand the steady decrease in the
      layer thickness (currently <= 1 mm) has improved the resolution of volume data
      sets and on the other hand there has been significant progress in postprocessing.
      PERFORMANCE: Numerous studies have recently shown that the significance of CTC in
      the detection of advanced adenomas is similar to conventional colonoscopy.
      ACHIEVEMENTS: Meanwhile CT colonography is now a routine investigation method
      established in both symptomatic and asymptomatic patients (screening). PRACTICAL
      RECOMMENDATIONS: Study data now clearly show that CTC, as an alternative to
      conventional colonoscopy, is a powerful method for investigation of colorectal
      cancer. To achieve good results adequate preparation including fecal tagging,
      standardized technical procedures during the investigation and expertise in both
      2D and 3D reading are essential.

PMID- 22622414
TI  - [Diagnosis and differential diagnosis of Graves' orbitopathy in MRI].
AB  - Imaging of Graves' orbitopathy (GO) includes radiological and nuclear medicine
      procedures. Depending on the method used they provide information about the
      distribution and activity of the disease. Magnetic resonance imaging (MRI) is not
      only a helpful tool for making the diagnosis it also enables differentiation of
      the active and inactive forms of GO due to intramuscular edema. The modality is
      therefore appropriate to evaluate the disease activity and the course of therapy.
      The disease leads to the typical enlargement of the muscle bodies of the
      extraocular muscles. The inferior rectus, medial rectus and levator palpebrae
      muscles are mostly involved. Signal changes of the intraconal and extraconal fat
      tissue are possible and a bilateral manifestation is common. The differential
      diagnosis includes inflammatory diseases and tumors, of which orbital pseudotumor
      (idiopathic, unspecific orbital inflammation), ocular myositis and orbital
      lymphoma are the most important. The specific patterns (localization, involvement
      of orbital structures and signal changes) can be differentiated by MRI.

PMID- 22622416
TI  - Sustained beta-catenin activity in dermal fibroblasts is sufficient for skin
      fibrosis.

PMID- 22622417
TI  - The expression of epidermal lipoxygenases and transglutaminase-1 is perturbed by
      NIPAL4 mutations: indications of a common metabolic pathway essential for skin
      barrier homeostasis.
AB  - Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of skin
      barrier diseases due inter alia to mutations in transglutaminase-1 (TGM1), in
      lipoxygenases (LOXs) of the hepoxilin pathway, and in ichthyin, a putative Mg(2+)
      transporter encoded by the NIPAL4 gene. In search of a common pathogenic pathway
      for ARCI, we investigated the epidermal expression of TGM1, 12R-LOX, eLOX-3, and
      ichthyin in skin biopsies from four healthy controls and nine patients with ARCI.
      In healthy skin, TGM1, ichthyin, and the LOX enzymes were predominantly expressed
      in the upper epidermis where colocalization signals could also be demonstrated by
      in situ proximity ligation assay. In patients with ALOX12B mutations and abnormal
      12R-LOX expression, the colocalization signal for eLOX-3 and TGM1 was increased 4
      fold. In contrast, patients with NIPAL4 mutations and abnormal ichthyin
      expression showed increased 12R-LOX and eLOX-3 staining and a colocalization
      signal of these LOXs that was three times the normal intensity. Treatment of
      these patients with a retinoid-mimetic drug, liarozole, normalized the expression
      of 12R-LOX and attenuated the colocalization signal. Altogether, our data
      indicate that ichthyin and TGM1 are functionally closely related in the lipid
      processing and that this metabolic pathway can be modified by retinoids.

PMID- 22622418
TI  - Immunogenicity and safety of seasonal influenza vaccination in patients with
      classic Kaposi's sarcoma.
AB  - Classic Kaposi's sarcoma (cKS) is a human herpesvirus-8 (HHV-8)-associated lympho
      angioproliferative tumor typically occurring in the elderly. It is associated
      with HHV-8-driven perturbed balance of peripheral B-cell subsets, which may have
      an impact on immune responses to antigenic stimulation. We took advantage of the
      common practice of cKS patients to undergo seasonal influenza vaccination because
      of advanced age and analyzed the immunogenicity and safety of licensed trivalent
      influenza vaccine in 46 cKS patients and 44 matched controls. Licensure criteria
      for immunogenicity were fulfilled in both groups. Four weeks after vaccination,
      hemagglutination-inhibition antibody titers against each viral strain contained
      in the vaccine increased in patients and controls (all P<0.001). Protection
      against at least one strain was achieved by 96% of cKS and 91% of control
      subjects. Protection against all strains persisted after 12 weeks, demonstrating
      a long-lasting response to vaccination. The vaccine was equally well tolerated by
      patients and controls, as assessed by evaluating solicited local and systemic
      reactions to the vaccine, and appearance or increase of antinuclear
      autoantibodies. HHV-8 virological rebound was observed in four cKS patients, but
      was not accompanied by progression of KS lesions. We conclude that seasonal
      influenza vaccine given to cKS patients is immunogenic and safe.

PMID- 22622420
TI  - Genetics of psoriasis: evidence for epistatic interaction between skin barrier
      abnormalities and immune deviation.
AB  - Psoriasis was until recently regarded as a T-cell-driven disease with presumed
      (auto)immune mechanisms as its primary cause. This view was supported by clinical
      data and genetic studies that identified risk factors functioning in adaptive and
      innate immunity, such as HLA-C*06, ERAP1, the IL-23 pathway, and NF-k B
      signaling. Candidate gene approaches and genome-wide association studies,
      however, have identified copy number polymorphisms of the b-defensin cluster and
      deletion of late cornified envelope (LCE) 3B and 3C genes (LCE3C_LCE3B-del) as
      psoriasis risk factors.As these genes are expressed in epithelial cells and not
      by the immune system, these findings may cause a change of paradigm for
      psoriasis, not unlike the reported filaggrin association that has profoundly
      changed the views on atopic dermatitis. In addition to genetic polymorphisms of
      the immune system, genetic variations affecting the skin barrier are likely to
      contribute to psoriasis. Recent studies have shown epistatic interactions
      involving HLA-C*06, ERAP1, and LCE3C_LCE3B-del, which makes psoriasis a unique
      model to investigate genetic and biological interactions of associated genes in a
      complex disease. We present a model for disease initiation and perpetuation,
      which integrates the available genetic, immunobiological, and clinical data.

PMID- 22622419
TI  - Stromal fibroblast-specific expression of ADAM-9 modulates proliferation and
      apoptosis in melanoma cells in vitro and in vivo.
AB  - ADAMs are members of the zinc metalloproteinase superfamily characterized by the
      presence of disintegrin and metalloprotease domains. In human melanoma, ADAM-9 is
      expressed in focalized areas of the tumor-stroma border in both melanoma and
      stromal cells. However, the role of ADAM-9 in melanoma progression remains
      elusive. To analyze the role of stromal-derived ADAM-9 for the growth and
      survival of melanoma cells, we have used in vitro coculture systems of melanoma
      cells and ADAM-9(-/-) fibroblasts. Coculture of melanoma cells in the presence of
      ADAM-9(-/-) fibroblasts led to increased melanoma cell proliferation and reduced
      apoptosis as compared with control cocultures. We identified TIMP-1 and sTNFRI as
      the two relevant factors expressed in increased amounts in culture supernatants
      from ADAM-9(-/-) fibroblasts. TIMP-1 was associated with induced melanoma cell
      proliferation, whereas soluble TNFR1 mediated the reduced cellular apoptosis in
      vitro. In vivo, injection of murine melanoma cells into the flank of ADAM-9(-/-)
      animals resulted in the development of significantly larger tumors than in wild
      type animals as a result of increased proliferation and decreased apoptosis of
      melanoma cells. Taken together, stromal expression of ADAM-9 during melanoma
      development modulates the expression of TIMP-1 and sTNFR1, which in turn affect
      tumor cell proliferation and apoptosis.

PMID- 22622421
TI  - Mutations in the gamma-secretase genes NCSTN, PSENEN, and PSEN1 underlie rare
      forms of hidradenitis suppurativa (acne inversa).

PMID- 22622422
TI  - TGM5 mutations impact epidermal differentiation in acral peeling skin syndrome.
AB  - Acral peeling skin syndrome (APSS) is an autosomal recessive skin disorder
      characterized by acral blistering and peeling of the outermost layers of the
      epidermis. It is caused by mutations in the gene for transglutaminase 5, TGM5.
      Here, we report on clinical and molecular findings in 11 patients and extend the
      TGM5 mutation database by four, to our knowledge, previously unreported
      mutations: p.M1T, p.L41P, p.L214CfsX15, and p.S604IfsX9. The recurrent mutation
      p.G113C was found in 9 patients, but also in 3 of 100 control individuals in a
      heterozygous state, indicating that APSS might be more widespread than hitherto
      expected. Using quantitative real-time PCR, immunoblotting, and
      immunofluorescence analysis, we demonstrate that expression and distribution of
      several epidermal differentiation markers and corneodesmosin (CDSN) is altered in
      APSS keratinocytes and skin. Although the expression of transglutaminases 1 and 3
      was not changed, we found an upregulation of keratin 1, keratin 10, involucrin,
      loricrin, and CDSN, probably as compensatory mechanisms for stabilization of the
      epidermal barrier. Our results give insights into the consequences of TGM5
      mutations on terminal epidermal differentiation.

PMID- 22622423
TI  - Tonic inhibition of TRPV3 by Mg2+ in mouse epidermal keratinocytes.
AB  - The transient receptor potential vanilloid 3 channel (TRPV3) is abundantly
      expressed in epidermal keratinocytes and has important roles in sensory biology
      and skin health. Mg(2+) deficiency causes skin disorders under certain
      pathological conditions such as type 2 diabetes mellitus. In this study, we
      investigated the effect of Mg(2+) on TRPV3 in primary epidermal keratinocytes.
      Extracellular Mg(2+) ([Mg(2+)](o)) inhibited TRPV3-mediated membrane current and
      calcium influx. TRPV3 activation induced a calcium signaling pathway culminating
      in activation of the cAMP response element binding. TRPV3 inhibition by
      [Mg(2+)](o), the TRPV3 blocker ruthenium red, or TRPV3 siRNA suppressed this
      response. In TRPV3-expressing Chinese hamster ovary cells, both extracellular and
      intracellular Mg(2+) inhibited TRPV3 single-channel conductance, but not open
      probability. Neutralization of an aspartic acid residue (D641) in the
      extracellular pore loop or two acidic residues (E679, E682) in the inner pore
      region significantly attenuated the inhibitory effect of extracellular or
      intracellular Mg(2+) on TRPV3-mediated signaling, respectively. Our findings
      suggest that epidermal TRPV3 is tonically inhibited by both extracellular and
      intracellular Mg(2+), which act on both sides of the channel pore loop. Mg(2+)
      deficiency may promote the function of TRPV3 and contribute to the pathogenesis
      of skin diseases.

PMID- 22622424
TI  - Modulation of lymphocyte function in vivo via inhibition of calcineurin or purine
      synthesis in patients with atopic dermatitis.

PMID- 22622425
TI  - Anti-IL-17 receptor antibody AMG 827 leads to rapid clinical response in subjects
      with moderate to severe psoriasis: results from a phase I, randomized, placebo
      controlled trial.

PMID- 22622427
TI  - Galectin-1 in melanoma biology and related neo-angiogenesis processes.
AB  - Aggressiveness of advanced melanomas relates in part to their marked propensity
      to develop neoangiogenesis and metastases. Among its numerous pro-cancer roles,
      galectin (gal)-1 expressed and/or secreted by both cancer and endothelial cells
      stimulates proliferation and angiogenesis. This study first shows that gal-1 is
      more highly expressed at both mRNA and protein levels than its congeners in
      melanomas and particularly in advanced lesions. The roles of gal-1 were further
      investigated in vivo in the highly proliferating and vascularized
      pseudometastatic B16F10 mouse melanoma model using stable knockdown B16F10 cells
      and wild-type versus gal-1 knockout mice, and then in vitro in B16F10 tumoral and
      lung microvascular cells. Gal-1 depletion in the B16F10 tumor cells but not in
      the tumor-bearing mice significantly increased melanoma-bearing mice survival.
      Tumor-derived gal-1 thus seems to have more critical roles than the host-derived
      one. In fact, gal-1 displays distinct effects on the H-Ras-dependent p53/p21
      pathways: in primary lung microvessel endothelial cells, gal-1 seems to be
      involved in the maintenance of senescent status through the induction of both p53
      and p21 while it stimulates B16F10 cancer cell proliferation through a p53/p21
      decrease. Altogether, these data point to gal-1 as a potential target to combat
      melanomas.

PMID- 22622426
TI  - Ablation of the calcium-sensing receptor in keratinocytes impairs epidermal
      differentiation and barrier function.
AB  - The calcium-sensing receptor (CaR) has an essential role in mediating Ca(2+)
      induced keratinocyte differentiation in vitro. In this study, we generated
      keratinocyte-specific CaR knockout ((Epid)CaR(-/-)) mice to investigate the
      function of the CaR in epidermal development in vivo. (Epid)CaR(-/-) mice
      exhibited a delay in permeability barrier formation during embryonic development.
      Ion capture cytochemistry detected the loss of the epidermal Ca(2+) gradient in
      the (Epid)CaR(-/-) mice. The expression of terminal differentiation markers and
      key enzymes mediating epidermal sphingolipid transport and processing in the
      (Epid)CaR(-/-) epidermis was significantly reduced. The (Epid)CaR(-/-) epidermis
      displayed a marked decrease in the number of lamellar bodies (LBs) and LB
      secretion, thinner lipid-bound cornified envelopes, and a defective permeability
      barrier. Consistent with in vivo results, epidermal keratinocytes cultured from
      (Epid)CaR(-/-) mice demonstrated abnormal Ca(2+)(i) handling and diminished
      differentiation. The impairment in epidermal differentiation and permeability
      barrier in (Epid)CaR(-/-) mice maintained on a low calcium (0.02%) diet is more
      profound and persistent with age than in (Epid)CaR(-/-) mice maintained on a
      normal calcium (1.3%) diet. Deleting CaR perturbs the epidermal Ca(2+) gradient
      and impairs keratinocyte differentiation and permeability barrier homeostasis,
      indicating a key role for the CaR in normal epidermal development.

PMID- 22622428
TI  - Increased p63 phosphorylation marks early transition of epidermal stem cells to
      progenitors.

PMID- 22622429
TI  - Regulatory role for the profilaggrin N-terminal domain in epidermal homeostasis.
AB  - It is well known that profilaggrin, after its release from keratohyalin granules
      through dephosphorylation, becomes enzymatically processed into individual
      filaggrin monomers. The roles for filaggrin monomers in aggregating keratin
      filaments, as a component of the cornified cell envelope, and as a source of
      natural moisturizing factor are well established. A specific N-terminal fragment,
      called the PF-AB domain, becomes proteolytically released as well, but much less
      is known about its functional role in epidermal development. Here, the functional
      role of profilaggrin N-terminal (PF-N) domain was addressed by overexpressing
      three overlapping fragments from a lentiviral expression vector in the epidermis
      of living skin equivalents. The PF-N domain expression impaired the epidermal
      development through reducing keratinocyte proliferation and impairing
      differentiation. The expression of well-known differentiation markers
      profilaggrin, loricrin, and keratin 10 was considerably downregulated in PF-N
      domain overexpressing-skin equivalents. The activation of caspase 14 was also
      substantially affected. In contrast, total silencing of profilaggrin expression,
      obtained with a lentiviral miR vector, resulted in a hyperproliferative
      epidermis. We propose a hypothesis that profilaggrin AB domain provides a key
      feedback mechanism that controls epidermal homeostasis.

PMID- 22622431
TI  - Long-term effects of antibiotics on the elimination of chemical oxygen demand,
      nitrification, and viable bacteria in laboratory-scale wastewater treatment
      plants.
AB  - Antibiotics and other pharmaceuticals are contaminants of the environment because
      of their widespread use and incomplete removal by microorganisms during
      wastewater treatment. The influence of a mixture of ciprofloxacin (CIP),
      gentamicin (GM), sulfamethoxazole (SMZ)/trimethoprim (TMP), and vancomycin (VA),
      up to a final concentration of 40 mg/L, on the elimination of chemical oxygen
      demand (COD), nitrification, and survival of bacteria, as well as the elimination
      of the antibiotics, was assessed in a long-term study in laboratory treatment
      plants (LTPs). In the presence of 30 mg/L antibiotics, nitrification of
      artificial sewage by activated sludge ended at nitrite. Nitrate formation was
      almost completely inhibited. No nitrification at all was possible in the presence
      of 40 mg/L antibiotics. The nitrifiers were more sensitive to antibiotics than
      heterotrophic bacteria. COD elimination in antibiotic-stressed LTPs was not
      influenced by <=20 mg/L antibiotics. Addition of 30 mg/L antibiotic mixture
      decreased COD removal efficiency for a period, but the LTPs recovered. Similar
      results were obtained with 40 mg/L antibiotic mixture. The total viable count of
      bacteria was not affected negatively by the antibiotics. It ranged from 2.2 *
      10(6) to 8.2 * 10(6) colony-forming units per milliliter (CFU/mL) compared with
      the control at 1.4 * 10(6)-6.3 * 10(6) CFU/mL. Elimination of the four
      antibiotics during phases of 2.4-30 mg/L from the liquid was high for GM (70-90
      %), much lower for VA, TMP, and CIP (0-50 %), and highly fluctuating for SMZ (0
      95 %). The antibiotics were mainly adsorbed to the sludge and not biodegraded.

PMID- 22622432
TI  - Complete genome sequence of narcissus late season yellows virus infecting Chinese
      narcissus in China.
AB  - The complete genome sequence of a Chinese narcissus isolate of narcissus late
      season yellows virus from Zhangzhou, China (NLSYV-ZZ), was determined to be 9,651
      nucleotides in length, excluding the 3'-terminal poly (A) tail, by amplification
      and sequencing of virus RNA. The viral genome contains a single long open reading
      frame of 9,315 nucleotides encoding a polyprotein of 3,105 amino acids. The
      polyprotein was predicted to be cleaved into ten mature proteins by three viral
      proteases. Complete genome sequence comparison and phylogenetic analysis
      indicated that NLSYV-ZZ was most closely related to narcissus yellow stripe virus
      (NYSV), which was also isolated from narcissus. These viruses shared 69.9 %
      identity in their complete nucleotide sequences and 77.0 % identity in their
      polyprotein amino acid sequences.

PMID- 22622430
TI  - Side population cells from human melanoma tumors reveal diverse mechanisms for
      chemoresistance.
AB  - Side population (SP) cells are identified as cells capable of excluding the
      fluorescent Hoechst dye and anticancer drugs, and it represents hematopoietic
      stem cells and chemoresistant cells from several solid tumors. In this study, we
      confirmed the presence of SP cells in tumors from melanoma patients. Melanoma SP
      cells overexpressed ATP-binding-cassette (ABC) transporters, ABCB1 and ABCB5. We
      generated a direct in vivo xenograft model, and demonstrated that SP cells were
      resistant to paclitaxel, a substrate of ABCB1, both in vitro and in vivo.
      However, melanoma SP cells were also resistant to temozolomide, which is not a
      substrate for ABC transporters, through IL-8 upregulation. In addition, gene
      profiling studies identified three signaling pathways (NF-kappaB, alpha6-beta4
      integrin, and IL-1) as differentially upregulated in melanoma SP cells, and there
      was a significant increase of PCDHB11 and decrease of FUK and TBX2 in these
      cells. Therefore, we provide evidence that SP is an enriched source of
      chemoresistant cells in human melanomas, and suggest that the selected genes and
      signaling pathways of SP cells may be a potential target for effective melanoma
      therapies. To our knowledge, this is a previously unreported study to isolate SP
      cells from melanoma patients and to investigate the gene expression profiling of
      these cells.

PMID- 22622433
TI  - First report of bovine herpesvirus 5 in bull semen.
AB  - BoHV-5 was detected in one of several extended semen samples from a healthy donor
      bull during routine virus screening. This was achieved by polymerase chain
      reaction assay (PCR) and virus isolation, with primary identification by the
      fluorescent antibody test. The isolated virus, B4180, was characterized by
      sequencing a cloned fragment of the gC gene and by restriction enzyme analysis
      (REA). The nucleotide sequence shared 99 % similarity with published sequences of
      BoHV-5, and the REA showed that the isolate was of the BoHV-5a subtype. This
      study provides the first evidence of intermittent BoHV-5 shedding in bull semen
      as well as information about its geographic distribution.

PMID- 22622434
TI  - Does age matter? Age and rehabilitation of visual field disorders after brain
      injury.
AB  - Homonymous visual field disorders (HVFD) are frequent and disabling consequences
      of acquired brain injury, particularly in older age. Their rehabilitation is
      therefore of great importance. Compensatory oculomotor therapy has been found to
      be effective in improving the associated functional impairments in reading and
      visual exploration. But older age is commonly considered to adversely affect
      practice-dependent functional plasticity and, thus, functional and rehabilitation
      outcome after acquired brain injury. The effect of age in the compensatory
      treatment of HVFD, however, has never been investigated hitherto. It remains
      unknown whether age determines not only patients' functional impairments but also
      the rehabilitation outcome and the required amount of treatment. We therefore
      present the first study to determine the effect of age in 38 patients with HVFD
      receiving compensatory oculomotor treatment for their reading and visual
      exploration impairments. We investigated whether older patients with HVFD (1)
      show more pronounced impairments and less spontaneous adaptation, (2) show lesser
      compensatory treatment-related improvement in reading and visual exploration, and
      (3) require a higher amount of treatment than younger patients. Our main finding
      is that older patients achieve the same treatment-induced improvements in reading
      and visual exploration with the same amount of treatment as younger patients;
      severity of functional impairment also did not differ between older and younger
      patients, at least in reading. Age does not seem to be a critical factor
      determining the functional and rehabilitation outcome in the compensatory
      treatment of HVFD. Older age per se is not necessarily associated with a decline
      in practice-dependent functional plasticity and adaptation. To the contrary, the
      effectiveness of compensatory treatment to reduce the functional impairments to a
      similar extent in younger and older patients with HVFD adds to the growing
      evidence for a life-long potential for adaptation to the adverse effects of brain
      injury.

PMID- 22622435
TI  - Neural convergence for language comprehension and grammatical class production in
      highly proficient bilinguals is independent of age of acquisition.
AB  - In bilinguals, native (L1) and second (L2) languages are processed by the same
      neural resources that can be modulated by age of second language acquisition
      (AOA), proficiency level, and daily language exposure and usage. AOA seems to
      particularly affect grammar processing, where a complete neural convergence has
      been shown only in bilinguals with parallel language acquisition from birth.
      Despite the fact that proficiency-related neuroanatomical differences have been
      well documented in language comprehension (LC) and production, few reports have
      addressed the influence of language exposure. A still unanswered question
      pertains to the role of AOA, when proficiency is comparably high across
      languages, with respect to its modulator effects both on LC and production. Here,
      we evaluated with fMRI during sentence comprehension and verb and noun production
      tasks, two groups of highly proficient bilinguals only differing in AOA. One
      group learned Italian and Friulian in parallel from birth, whereas the second
      group learned Italian between 3 and 6 years. All participants were highly exposed
      to both languages, but more to Italian than Friulian. The results indicate a
      complete overlap of neural activations for the comprehension of both languages,
      not only in bilinguals from birth, but also in late bilinguals. A slightly extra
      activation in the left thalamus for the less-exposed language confirms that
      exposure may affect language processing. Noteworthy, we report for the first time
      that, when proficiency and exposure are kept high, noun and verb production
      recruit the same neural networks for L1 and L2, independently of AOA. These
      results support the neural convergence hypothesis.

PMID- 22622436
TI  - What colour does that feel? Tactile--visual mapping and the development of cross
      modality.
AB  - Humans share implicit preferences for cross-modal mappings (e.g., low pitch
      sounds are preferentially paired with darker colours). Individuals with
      synaesthesia experience cross-modal mappings to a conscious degree (e.g., they
      may see colours when they hear sounds). The neonatal synaesthesia hypothesis
      claims that all humans may be born with this explicit cross-modal perception,
      which dies out in most people through childhood, leaving only implicit
      associations in the average adult. Although there is evidence for decreasing
      cross-modality throughout early infancy, it is unclear whether this decline
      continues to take place throughout childhood and adolescence. This large-scale
      study had two goals. First, we aimed to establish whether human non-synaesthetes
      systematically map tactile and visual dimensions - a combination that has rarely
      been studied. Second, we asked whether tactile-visual associations may be more
      pronounced in younger compared to older participants. 210 participants between
      the ages of 5-74 years assigned colours to tactile stimuli. Smoothness, softness
      and roundness of stimuli positively correlated with luminance of the chosen
      colour; and smoothness and softness also positively correlated with chroma.
      Moreover, tactile sensations were associated with specific colours (e.g.,
      softness with pink). There were no age differences for luminance effects. Chroma
      effects, however, were found exclusively in children and adolescents. Our
      findings are consistent with the neonatal synaesthesia hypothesis which suggests
      that all humans are born with strong cross-modal perception which is pruned away
      or inhibited throughout development. Moreover, the findings suggest that a
      decline of some forms of cross-modality may take place over a much longer time
      span than previously assumed.

PMID- 22622438
TI  - A graphene-cobalt oxide based needle electrode for non-enzymatic glucose
      detection in micro-droplets.
AB  - A novel graphene-cobalt oxide hybrid needle-like electrode was fabricated for non
      enzymatic glucose detection. Taking advantage of its small size, the needle
      electrode can probe glucose in a micro-droplet with high sensitivity.

PMID- 22622437
TI  - The effect of state anxiety on the online and offline control of fast target
      directed movements.
AB  - In target-directed aiming, afferent information is used to adjust limb
      trajectories during movement execution (i.e. online) and to enhance the
      programming of subsequent trials (i.e. offline). The objective of the present
      study was to determine the influence of state anxiety on both online and offline
      afferent information processing for the first time. Participants practiced either
      a directional aiming task (Experiment 1) or an amplitude aiming task (Experiment
      2) without anxiety before being transferred to a high anxiety condition. In both
      experiments, results revealed that anxiety resulted in a decrement in
      performance. Furthermore, use of afferent information to adjust movement
      trajectories online was disrupted when movements were performed with anxiety,
      whereas there were no differences in the offline processing of afferent
      information between the low anxiety and high anxiety conditions.

PMID- 22622439
TI  - Coinfection of Leptomonas seymouri and Leishmania donovani in Indian
      leishmaniasis.
AB  - Leishmania donovani is considered the causative organism of visceral
      leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL). Testing of
      4/29 DNA samples from VL and PKDL patients as well as 2/7 field isolates showed
      an aberrant internal transcribed spacer 1 (ITS1) restriction fragment length
      polymorphism (RFLP) pattern, which upon sequencing strongly matched Leptomonas
      seymouri, thus confirming its presence in Indian leishmaniasis.

PMID- 22622440
TI  - Nonclinical selection criteria for maximizing yield of nucleic acid amplification
      tests in tuberculosis diagnosis.
AB  - In spite of the excellent performance of rapid tuberculosis (TB) nucleic acid
      amplification (NAA) tests and the clear benefits of immediate diagnosis of TB
      disease, NAA tests frequently are not used in the diagnosis of pulmonary TB
      cases, particularly TB cases with smear-negative sputa. Public health
      laboratories primarily perform TB NAA tests only on a targeted subset of
      specimens, usually including those that are smear positive and those for which a
      clinician has specifically requested NAA testing. As an alternative to targeted
      testing, some laboratories use TB NAA tests universally for all respiratory
      specimens, though this practice can be prohibitively costly and can be associated
      with an increased frequency of false-positive results due to testing of lower
      risk patients. We propose a strategy for identifying individuals for NAA testing
      on the basis of nonclinical risk criteria that are routinely provided on the test
      requisition form, such as type of health care facility from which the specimen is
      received and patient age group. Use of this strategy at the Massachusetts
      Department of Public Health Laboratory would allow for NAA test identification of
      approximately 54 (74%) of 72 culture-positive pulmonary TB cases over a 1-year
      period while requiring NAA testing for only 933 (17%) of 5,469 individuals
      submitting respiratory specimens. We demonstrate that use of nonclinical NAA test
      selection criteria is an effective strategy for maximizing the number of TB cases
      that can be rapidly identified while minimizing the number of specimens that must
      be tested.

PMID- 22622441
TI  - Simian genogroup I picobirnaviruses: prevalence, genetic diversity, and zoonotic
      potential.
AB  - We previously reported the first detection of simian picobirnaviruses (PBVs) by
      polyacrylamide gel electrophoresis in fecal specimens of two monkeys with
      diarrhea in China. We now report the detection of genogroup I PBVs in 48% (44/92)
      of the fecal specimens by reverse transcriptase PCR (RT-PCR) and amplicon
      sequencing using primers specific for the RNA-dependent RNA polymerase (RDRP)
      gene. Molecular characterization of these 44 strains demonstrated both sequence
      conservation and diversity among simian PBVs and among simian, porcine, and human
      PBVs. We further determined full-length sequences of segment 2 of the two simian
      PBV strains, monkey/CHN-14/2002 and monkey/CHN-49/2002, and demonstrated 52.5% to
      54.2% nucleotide sequence similarity to the corresponding gene of the bovine
      strain RUBV and the prototype human strain 1-CHN-97 of genogroup I PBVs and an
      even lower similarity (38.4%) to segment 2 of the prototype human genogroup II
      strain 4-GA-91. Further studies are needed to investigate the epidemiology and
      pathogenesis of PBVs in animals and humans.

PMID- 22622442
TI  - Rapid detection of Streptococcus pyogenes in pleural fluid samples from pediatric
      patients with empyema.
AB  - A total of 120 pleural fluid specimens from 113 pediatric patients were tested
      using two rapid antigen detection assays for Streptococcus pyogenes. Results were
      compared to culture, Gram stain, and PCR results. Each rapid antigen assay
      detected 9 out of 10 (90%) PCR-positive samples, with 100% specificity. These
      antigen detection assays are useful to provide microbiological diagnosis of
      empyema caused by S. pyogenes.

PMID- 22622443
TI  - Rectal screening for Klebsiella pneumoniae carbapenemases: comparison of real
      time PCR and culture using two selective screening agar plates.
AB  - Klebsiella pneumoniae carbapenemases (KPCs) have recently been described in
      Chicago, IL, especially among residents of long-term acute care hospitals
      (LTACHs). These patients are frequently transferred to local Chicago hospitals
      for higher acuity of medical care, and rapid detection and isolation of KPC
      colonized LTACH residents may interrupt the introduction of KPCs into acute care
      hospitals. We evaluated the performance of a real-time PCR for bla(KPC) from
      enrichment broth versus direct plating of rectal surveillance swabs on two
      selective culture media, CHROMagar extended-spectrum-beta-lactamase (ESBL) and
      vancomycin, amphotericin B, ceftazidime, and clindamycin (VACC) plates. Rectal
      surveillance swabs were collected as part of a point prevalence study of KPC
      carriage rates among 95 residents of two Chicago area LTACHs. Discrepant results
      between PCR and culture were resolved by subculturing the enrichment broth.
      Overall, 66 of 95 patients (69.5%) were colonized with KPCs, using the cumulative
      results of culture as a reference standard. Real-time PCR from enrichment broth
      was positive in 64 of 66 (97%) colonized patients, including nine surveillance
      swabs that were missed by both selective culture media. PCR demonstrated higher
      sensitivity, 97.0%, than culture using either CHROMagar or VACC plates (both with
      sensitivity of 77.3%). In addition, turnaround time was significantly shorter for
      the PCR-based method than for culture, with a mean of 24 h versus 64 to 72 h for
      CHROMagar and VACC plates (P < 0.0001). Overall, PCR for bla(KPC) represents the
      best screening test for KPCs with significantly higher sensitivity and with less
      hands-on time, resulting in a shorter time to results.

PMID- 22622444
TI  - Invasive Apophysomyces variabilis infection in a burn patient.
AB  - Apophysomyces variabilis is an emerging fungal pathogen that can cause
      significant infections in immunocompetent patients. We report a case of A.
      variabilis invasive wound infection in a 21-year-old male after a self-inflicted
      burn injury.

PMID- 22622445
TI  - Evaluation of the New NucliSENS EasyQ KPC test for rapid detection of Klebsiella
      pneumoniae carbapenemase genes (blaKPC).
AB  - KPC-type carbapenemases are emerging in Klebsiella pneumoniae and other Gram
      negative pathogens worldwide. Rapid and sensitive detection of these resistance
      determinants has become relevant to clinical management and infection control. We
      evaluated the bioMerieux EasyQ real-time PCR assay for bla(KPC) detection with
      300 members of the Enterobacteriaceae, including 29 control strains producing
      known carbapenemases and 271 nonreplicate clinical isolates. The EasyQ assay
      correctly detected all of the 111 isolates harboring bla(KPC) genes, with no
      false positives, and results were available within 2 h.

PMID- 22622446
TI  - Sydney M. Finegold.

PMID- 22622448
TI  - Community-associated meticillin-resistant Staphylococcus aureus: the case for a
      genotypic definition.
AB  - BACKGROUND: New distinct strains of community-associated meticillin-resistant
      Staphylococcus aureus (CA-MRSA) have emerged as a cause of infection in
      previously healthy individuals in community settings. It is important to identify
      CA-MRSA for clinical management, epidemiological analysis, infection prevention
      and control, and regulatory reporting, but definitions and nomenclature of these
      strains are confused. AIM: To review attempts to define CA-MRSA and propose a new
      definition. METHODS: Non-systematic review. FINDINGS: Epidemiological definitions
      were useful for differentiating CA-MRSA and healthcare-associated (HA)-MRSA
      strain types in the past. However, although HA-MRSA strain types are rarely
      transmitted in the community, CA-MRSA strains have started to be transmitted in
      healthcare facilities, so epidemiological definitions are breaking down. CA-MRSA
      are community strains of S. aureus that have acquired the meticillin resistance
      gene, mecA. They are distinct from HA-MRSA and should be defined genetically.
      This may be done by combining genotypic typing by multi-locus sequence or spa
      with analysis of the staphylococcal cassette chromosome mec. Carriage of Panton
      Valentine leukocidin or antimicrobial susceptibility profiles can be useful
      indicators of CA-MRSA but should not be used for their definition. CONCLUSION:
      For full assessment of their epidemiology, MRSA infections should be
      characterized as: (1) caused by HA- or CA-MRSA strain types; (2) acquired in
      community or healthcare settings; and (3) onset in the community or healthcare
      facility.

PMID- 22622447
TI  - Prevalence of Trichomonas vaginalis and coinfection with Chlamydia trachomatis
      and Neisseria gonorrhoeae in the United States as determined by the Aptima
      Trichomonas vaginalis nucleic acid amplification assay.
AB  - Our aim was to determine Trichomonas vaginalis prevalence using the Aptima
      Trichomonas vaginalis assay (ATV; Gen-Probe) and the prevalence of Chlamydia
      trachomatis and Neisseria gonorrhoeae coinfections in U.S. women undergoing
      screening for C. trachomatis/N. gonorrhoeae. Discarded urogenital samples from
      7,593 women (18 to 89 years old) undergoing C. trachomatis/N. gonorrhoeae
      screening using the Aptima Combo 2 assay (Gen-Probe) in various clinical settings
      were tested with ATV. Overall, T. vaginalis, C. trachomatis, and N. gonorrhoeae
      prevalences were 8.7%, 6.7%, and 1.7%, respectively. T. vaginalis was more
      prevalent than C. trachomatis or N. gonorrhoeae in all age groups except the 18-
      to 19-year-old group. The highest T. vaginalis prevalence was in women >= 40
      years old (>11%), while the highest C. trachomatis prevalence (9.2%) and N.
      gonorrhoeae prevalence (2.2%) were in women <30 years old. Coinfection
      prevalences were 1.3% for C. trachomatis/T. vaginalis, 0.61% for C.
      trachomatis/N. gonorrhoeae and N. gonorrhoeae/T. vaginalis, and 0.24% for C.
      trachomatis/N. gonorrhoeae/T. vaginalis and highest in women <30 years old. T.
      vaginalis prevalence differed by race/ethnicity, with the highest prevalence in
      black women (20.2%). T. vaginalis prevalence ranged from 5.4% in family planning
      clinics to 22.3% in jails. Multivariate analysis determined that ages of >= 40
      years, black race, and patient locations were significantly associated with T.
      vaginalis infection. T. vaginalis is the most common sexually transmitted
      infection (STI) in women of >40 years, while C. trachomatis and N. gonorrhoeae
      prevalence is lowest in that age group. Higher T. vaginalis prevalence in women
      of >40 years is probably attributed to the reason for testing, i.e., symptomatic
      status versus routine screening in younger women. Coinfections were relatively
      low. High T. vaginalis prevalence in all age groups suggests that women screened
      for C. trachomatis/N. gonorrhoeae, whether asymptomatic or symptomatic, should be
      screened for T. vaginalis.

PMID- 22622449
TI  - A gold(I)-catalyzed route to alpha-sulfenylated carbonyl compounds from
      propargylic alcohols and aryl thiols.
AB  - A one-step atom efficient gold(I)-catalyzed route to alpha-sulfenylated ketones
      and aldehydes from propargylic alcohols and aryl thiols is described.

PMID- 22622450
TI  - Hydrothermal and solid-state transformation of ruthenium-supported Keggin-type
      heteropolytungstates [XW11O39{Ru(II)(benzene)(H2O)}]n- (X = P (n = 5), Si (n =
      6), Ge (n = 6)) to ruthenium-substituted Keggin-type heteropolytungstates.
AB  - A new pathway for the preparation of mono-ruthenium (Ru)(iii)-substituted Keggin
      type heteropolytungstates with an aqua ligand, [PW(11)O(39)Ru(iii)(H(2)O)](4-)
      (1a), [SiW(11)O(39)Ru(iii)(H(2)O)](5-) (1b) and [GeW(11)O(39)Ru(iii)(H(2)O)](5-)
      (1c), using [Ru(ii)(benzene)Cl(2)](2) as a Ru source was described. Compounds 1a
      1c were prepared by reacting [XW(11)O(39)](n-) (X = P, Si and Ge) with
      [Ru(ii)(benzene)Cl(2)](2) under hydrothermal condition and were isolated as
      caesium salts. Ru(benzene)-supported heteropolytungstates,
      [PW(11)O(39){Ru(ii)(benzene)(H(2)O)}](5-) (2a),
      [SiW(11)O(39){Ru(ii)(benzene)(H(2)O)}](6-) (2b) and
      [GeW(11)O(39){Ru(ii)(benzene)(H(2)O)}](6-) (2c), were first produced in the
      reaction media, and then transformed to 1a, 1b and 1c, respectively, under
      hydrothermal conditions. Calcination of Ru(benzene)-supported
      heteropolytungstates, 2a, 2b and 2c, in the solid state produced mixtures of 1a,
      1b and 1c with CO (carbon monoxide)-coordinated complexes,
      [PW(11)O(39)Ru(ii)(CO)](5-) (4a), [SiW(11)O(39)Ru(ii)(CO)](6-) (4b) and
      [GeW(11)O(39)Ru(ii)(CO)](6-) (4c), respectively. From comparison of their
      catalytic activities in water oxidation reaction, it was indicated that ruthenium
      should be incorporated in the heteropolytungstate in order to promote catalytic
      activity.

PMID- 22622451
TI  - The role of lymphatics in renal inflammation.
AB  - Progressive renal diseases are characterized by tubulointerstitial inflammatory
      cell recruitment, tubular atrophy and fibrosis. Various aspects of the
      recruitment of leukocytes have been extensively studied, but the exit routes
      (i.e. the lymphatic vessels and their biology) have only recently found
      attention. Similar to the recruitment of inflammatory cells, the exit is
      coordinated by an orchestrated interaction of chemotactic cytokines and adhesion
      molecules. During inflammatory injury, new routes are created by the de novo
      formation of lymphatic vessels, i.e. neolymphangiogenesis. These newly formed
      lymphatic vessels help to cope with the increase in interstitial fluid related to
      inflammation. Here, we review some aspects of lymphatic biology and the current
      knowledge about lymphatic vessels in renal inflammation.

PMID- 22622453
TI  - The 9p21 coronary artery disease locus and kidney dysfunction in patients with
      Type 2 diabetes mellitus.
AB  - BACKGROUND: We investigated whether the coronary artery disease (CAD) locus on
      chromosome 9p21 (as represented by single nucleotide polymorphism rs2383206) is
      associated with low estimated glomerular filtration rate (eGFR) or increased
      urinary albumin excretion in patients with Type 2 diabetes mellitus (T2DM).
      METHODS: Four samples, including a total of 3167 patients, were studied. The
      presence of low eGFR (<60 mL/min/1.73m(2)) was estimated from serum creatinine by
      means of the Modification of Diet in Renal Disease Study equation. Increased
      urinary albumin excretion was defined as an albumin-creatinine ratio (ACR) >=2.5
      mg/mmol in men and >=3.5 mg/mmol in women. RESULTS: No association was found
      between rs2383206 and low eGFR or increased ACR in each sample as well as in a
      pooled analysis (overall odds ratio = 1.07, 95% confidence interval 0.94-1.22, P
      = 0.31 and overall odds ratio = 1.00, 95% confidence interval 0.90-1.12, P =
      0.95, respectively). No interaction was observed between rs2383206 and poor
      glycemic control [HbA1c was above the median in the pooled sample (7.7%) in
      modulating eGFR or ACR (P for interaction = 0.42 and 0.90, respectively)].
      CONCLUSION: Variability at the 9p21 CAD locus is unlikely to play a role in
      modulating susceptibility to kidney dysfunction in patients with T2DM.

PMID- 22622452
TI  - Predictors of haemoglobin levels and resistance to erythropoiesis-stimulating
      agents in patients treated with low-flux haemodialysis, haemofiltration and
      haemodiafiltration: results of a multicentre randomized and controlled trial.
AB  - BACKGROUND: Predictors of haemoglobin (Hb) levels and resistance to
      erythropoiesis-stimulating agents (ESAs) in dialysis patients have not yet been
      clearly defined. Some mainly uncontrolled studies suggest that online
      haemodiafiltration (HDF) may have a beneficial effect on Hb, whereas no data are
      available concerning online haemofiltration (HF). The objectives of this study
      were to evaluate the effects of convective treatments (CTs) on Hb levels and ESA
      resistance in comparison with low-flux haemodialysis (HD) and to evaluate the
      predictors of these outcomes. METHODS: Primary multivariate analysis was made of
      a pre-specified secondary outcome of a multicentre, open-label, randomized
      controlled study in which 146 chronic HD patients from 27 Italian centres were
      randomly assigned to HD (70 patients) or CTs: online pre-dilution HF (36
      patients) or online pre-dilution HDF (40 patients). RESULTS: CTs did not affect
      Hb levels (P = 0.596) or ESA resistance (P = 0.984). Hb correlated with
      polycystic kidney disease (P = 0.001), C-reactive protein (P = 0.025), ferritin
      (P = 0.018), ESA dose (P < 0.001) and total cholesterol (P = 0.021). The
      participating centres were the main source of Hb variability (partial eta(2)
      0.313, P < 0.001). ESA resistance directly correlated with serum ferritin (P =
      0.030) and beta2 microglobulin (P = 0.065); participating centres were again a
      major source of variance (partial eta(2) 0.367, P < 0.001). Transferrin
      saturation did not predict either outcome variables (P = 0.277 and P = 0.170).
      CONCLUSIONS: In comparison with low-flux HD, CTs did not significantly improve Hb
      levels or ESA resistance. The main sources of variability were participating
      centres, ESA dose and the underlying disease.

PMID- 22622454
TI  - The question of primary lipid nephrotoxicity.

PMID- 22622455
TI  - Nicorandil, a K(atp) channel opener, alleviates chronic renal injury by targeting
      podocytes and macrophages.
AB  - Nicorandil exhibits a protective effect in the vascular system, which is thought
      to be due to vasodilatation from opening ATP-dependent potassium channels and
      donation of nitric oxide. Recently, nicorandil was shown to be renoprotective in
      models of acute kidney injury and glomerulonephritis. However, the specific
      mechanisms of renoprotection are unclear. We evaluated the effect of nicorandil
      on the rat remnant kidney model of chronic kidney disease. Blood pressure was
      unchanged by a 10-wk course of nicorandil, while albuminuria was significantly
      reduced. Glomerular injury and tubulointerstitial injury were also ameliorated by
      nicorandil. Oxidative stress, as noted by renal nitrotyrosine level and urine 8
      hydroxy-2'-deoxyguanosine, were elevated in this model and was significantly
      reduced by nicorandil treatment. Treatment was associated with maintenance of the
      mitochondrial antioxidant, manganese SOD, in podocytes and with suppression of
      xanthine oxidase expression in infiltrating macrophages. Interestingly, these two
      cell types express sulfonylurea receptor 2 (SUR2), a binding site of nicorandil
      in the ATP-dependent K channel. Consistently, we found that stimulating SUR2 with
      nicorandil prevented angiotensin II-mediated upregulation of xanthine oxidase in
      the cultured macrophage, while xanthine oxidase expression was rather induced by
      blocking SUR2 with glibenclamide. In conclusion, nicorandil reduces albuminuria
      and ameliorates renal injury by blocking oxidative stress in chronic kidney
      disease.

PMID- 22622456
TI  - A urine-concentrating defect in 11beta-hydroxysteroid dehydrogenase type 2 null
      mice.
AB  - In aldosterone target tissues, 11beta-hydroxysteroid dehydrogenase type 2
      (11betaHSD2) is coexpressed with mineralocorticoid receptors (MR) and protects
      the receptor from activation by glucocorticoids. Null mutations in the encoding
      gene, HSD11B2, cause apparent mineralocorticoid excess, in which hypertension is
      thought to reflect volume expansion secondary to sodium retention. Hsd11b2(-/-)
      mice are indeed hypertensive, but impaired natriuretic capacity is associated
      with significant volume contraction, suggestive of a urine concentrating defect.
      Water turnover and the urine concentrating response to a 24-h water deprivation
      challenge were therefore assessed in Hsd11b2(-/-) mice and controls. Hsd11b2(-/-)
      mice have a severe and progressive polyuric/polydipsic phenotype. In younger mice
      (~2 mo of age), polyuria was associated with decreased abundance of aqp2 and aqp3
      mRNA. The expression of other genes involved in water transport (aqp4, slc14a2,
      and slc12a2) was not changed. The kidney was structurally normal, and the
      concentrating response to water deprivation was intact. In older Hsd11b2(-/-)
      mice (>6 mo), polyuria was associated with a severe atrophy of the renal medulla
      and downregulation of aqp2, aqp3, aqp4, slc14a2, and slc12a2. The concentrating
      response to water deprivation was impaired, and the natriuretic effect of the
      loop diuretic bumetanide was lost. In older Hsd11b2(-/-) mice, the V2 receptor
      agonist desmopressin did not restore full urine concentrating capacity. We find
      that Hsd11b2(-/-) mice develop nephrogenic diabetes insipidus. Gross changes to
      renal structure are observed, but these were probably secondary to sustained
      polyuria, rather than of developmental origin.

PMID- 22622457
TI  - Estrogen protects renal endothelial barrier function from ischemia-reperfusion in
      vitro and in vivo.
AB  - Emerging evidence suggests that renal endothelial function may be altered in
      ischemia-reperfusion injury. Acute kidney injury is sexually dimorphic, and
      estrogen protects renal tubular function after experimental ischemic injury. This
      study tested the hypothesis that during ischemia-reperfusion, estrogen alters
      glomerular endothelial function to prevent hyperpermeability. Glomerular
      endothelial cells were exposed to 8-h oxygen-glucose deprivation (OGD) followed
      by 4- and 8-h reoxygenation-glucose repletion. After 4-h reoxygenation-glucose
      repletion, transendothelial permeability to Ficoll-70 was reduced, and
      transendothelial resistance increased, by 17beta-estradiol vs. vehicle treatment
      during OGD (OGD-vehicle: 91.0 +/- 11.8%, OGD-estrogen: 102.6 +/- 10.8%, P <
      0.05). This effect was reversed by coadministration of G protein-coupled receptor
      30 (GPR30) antagonist G15 with 17beta-estradiol (OGD-estrogen-G15: 89.5 +/- 6.9,
      P < 0.05 compared with 17beta-estradiol). To provide preliminary confirmation of
      this result in vivo, Ficoll-70 was administered to mice 24 h after cardiac arrest
      and cardiopulmonary resuscitation (CA/CPR). Blood urea nitrogen (BUN) and serum
      creatinine (SCr) in these mice were elevated within 12 h following CA/CPR and
      reduced at 24 h by pretreatment with 17beta-estradiol (BUN/SCr 17beta-estradiol:
      34 +/- 19/0.2 +/- 0.1 vehicle: 92 +/- 49/0.5 +/- 0.3, n = 8-12, P < 0.05).
      Glomerular sieving of Ficoll 70 was increased by CA/CPR within 2 h of injury and
      17beta-estradiol treatment (theta; 17beta-estradiol: 0.74 +/- 0.26 vs. vehicle:
      1.05 +/- 0.53, n = 14-15, P < 0.05). These results suggest that estrogen reduces
      postischemic glomerular endothelial hyperpermeability at least in part through
      GPR30 and that estrogen may regulate post CA/CPR glomerular permeability in a
      similar fashion in vivo.

PMID- 22622458
TI  - Going with the flow: regulation of the thick ascending limb.

PMID- 22622459
TI  - Tissue kallikrein activation of the epithelial Na channel.
AB  - Epithelial Na Channels (ENaC) are responsible for the apical entry of Na(+) in a
      number of different epithelia including the renal connecting tubule and cortical
      collecting duct. Proteolytic cleavage of gamma-ENaC by serine proteases,
      including trypsin, furin, elastase, and prostasin, has been shown to increase
      channel activity. Here, we investigate the ability of another serine protease,
      tissue kallikrein, to regulate ENaC. We show that excretion of tissue kallikrein,
      which is secreted into the lumen of the connecting tubule, is stimulated
      following 5 days of a high-K(+) or low-Na(+) diet in rats. Urinary proteins
      reconstituted in a low-Na buffer activated amiloride-sensitive currents (I(Na))
      in ENaC-expressing oocytes, suggesting an endogenous urinary protease can
      activate ENaC. We next tested whether tissue kallikrein can directly cleave and
      activate ENaC. When rat ENaC-expressing oocytes were exposed to purified tissue
      kallikrein from rat urine (RTK), ENaC currents increased threefold in both the
      presence and absence of a soybean trypsin inhibitor (SBTI). RTK and trypsin both
      decreased the apparent molecular mass of cleaved cell-surface gamma-ENaC, while
      immunodepleted RTK produced no shift in apparent molecular mass, demonstrating
      the specificity of the tissue kallikrein. A decreased effect of RTK on Xenopus
      ENaC, which has variations in the putative prostasin cleavage sites in gamma
      ENaC, suggests these sites are important in RTK activation of ENaC. Mutating the
      prostasin site in mouse gamma-ENaC (gammaRKRK186QQQQ) abolished ENaC activation
      and cleavage by RTK while wild-type mouse ENaC was activated and cleaved similar
      to that of the rat. We conclude that tissue kallikrein can be a physiologically
      relevant regulator of ENaC activity.

PMID- 22622460
TI  - Early superoxide scavenging accelerates renal microvascular rarefaction and
      damage in the stenotic kidney.
AB  - Renal artery stenosis (RAS), the main cause of chronic renovascular disease
      (RVD), is associated with significant oxidative stress. Chronic RVD induces renal
      injury partly by promoting renal microvascular (MV) damage and blunting MV repair
      in the stenotic kidney. We tested the hypothesis that superoxide anion plays a
      pivotal role in MV dysfunction, reduction of MV density, and progression of renal
      injury in the stenotic kidney. RAS was induced in 14 domestic pigs and observed
      for 6 wk. Seven RAS pigs were chronically treated with the superoxide dismutase
      mimetic tempol (RAS+T) to reduce oxidative stress. Single-kidney hemodynamics and
      function were quantified in vivo using multidetector computer tomography (CT) and
      renal MV density was quantified ex vivo using micro-CT. Expression of angiogenic,
      inflammatory, and apoptotic factors was measured in renal tissue, and renal
      apoptosis and fibrosis were quantified in tissue sections. The degree of RAS and
      blood pressure were similarly increased in RAS and RAS+T. Renal blood flow (RBF)
      and glomerular filtration rate (GFR) were reduced in the stenotic kidney (280.1
      +/- 36.8 and 34.2 +/- 3.1 ml/min, P < 0.05 vs. control). RAS+T kidneys showed
      preserved GFR (58.5 +/- 6.3 ml/min, P = not significant vs. control) but a
      similar decreases in RBF (293.6 +/- 85.2 ml/min) and further decreases in MV
      density compared with RAS. These changes were accompanied by blunted angiogenic
      signaling and increased apoptosis and fibrosis in the stenotic kidney of RAS+T
      compared with RAS. The current study shows that tempol administration provided
      limited protection to the stenotic kidney. Despite preserved GFR, renal perfusion
      was not improved by tempol, and MV density was further reduced compared with
      untreated RAS, associated with increased renal apoptosis and fibrosis. These
      results suggest that a tight balance of the renal redox status is necessary for a
      normal MV repair response to injury, at least at the early stage of RVD, and
      raise caution regarding antioxidant strategies in RAS.

PMID- 22622462
TI  - Defective renal water handling in transgenic mice over-expressing human
      CD39/NTPDase1.
AB  - Ectonucleoside triphosphate diphosphohydrolase-1 hydrolyzes extracellular ATP and
      ADP to AMP. Previously, we showed that CD39 is expressed at several sites within
      the kidney and thus may impact the availability of type 2 purinergic receptor (P2
      R) ligands. Because P2-Rs appear to regulate urinary concentrating ability, we
      have evaluated renal water handling in transgenic mice (TG) globally
      overexpressing hCD39. Under basal conditions, TG mice exhibited significantly
      impaired urinary concentration and decreased protein abundance of AQP2 in the
      kidney compared with wild-type (WT) mice. Urinary excretion of total
      nitrates/nitrites was significantly higher in TG mice, but the excretion of AVP
      or PGE(2) was equivalent to control WT mice. There were no significant
      differences in electrolyte-free water clearance or fractional excretion of
      sodium. Under stable hydrated conditions (gelled diet feeding), the differences
      between the WT and TG mice were negated, but the decrease in urine osmolality
      persisted. When water deprived, TG mice failed to adequately concentrate urine
      and exhibited impaired AVP responses. However, the increases in urinary
      osmolalities in response to subacute dDAVP or chronic AVP treatment were similar
      in TG and WT mice. These observations suggest that TG mice have impaired urinary
      concentrating ability despite normal AVP levels. We also note impaired AVP
      release in response to water deprivation but that TG kidneys are responsive to
      exogenous dDAVP or AVP. We infer that heightened nucleotide scavenging by
      increased levels of CD39 altered the release of endogenous AVP in response to
      dehydration. We propose that ectonucleotidases and modulated purinergic signaling
      impact urinary concentration and indicate potential utility of targeted therapy
      for the treatment of water balance disorders.

PMID- 22622463
TI  - Mitochondrial aquaporin-8 in renal proximal tubule cells: evidence for a role in
      the response to metabolic acidosis.
AB  - Mitochondrial ammonia synthesis in proximal tubules and its urinary excretion are
      key components of the renal response to maintain acid-base balance during
      metabolic acidosis. Since aquaporin-8 (AQP8) facilitates transport of ammonia and
      is localized in inner mitochondrial membrane (IMM) of renal proximal cells, we
      hypothesized that AQP8-facilitated mitochondrial ammonia transport in these cells
      plays a role in the response to acidosis. We evaluated whether mitochondrial AQP8
      (mtAQP8) knockdown by RNA interference is able to impair ammonia excretion in the
      human renal proximal tubule cell line, HK-2. By RT-PCR and immunoblotting, we
      found that AQP8 is expressed in these cells and is localized in IMM. HK-2 cells
      were transfected with short-interfering RNA targeting human AQP8. After 48 h, the
      levels of mtAQP8 protein decreased by 53% (P < 0.05). mtAQP8 knockdown decreased
      the rate of ammonia released into culture medium in cells grown at pH 7.4 (-31%,
      P < 0.05) as well as in cells exposed to acid (-90%, P < 0.05). We also evaluated
      mtAQP8 protein expression in HK-2 cells exposed to acidic medium. After 48 h,
      upregulation of mtAQP8 (+74%, P < 0.05) was observed, together with higher
      ammonia excretion rate (+73%, P < 0.05). In vivo studies in NH(4)Cl-loaded rats
      showed that mtAQP8 protein expression was also upregulated after 7 days of
      acidosis in renal cortex (+51%, P < 0.05). These data suggest that mtAQP8 plays
      an important role in the adaptive response of proximal tubule to acidosis
      possibly facilitating mitochondrial ammonia transport.

PMID- 22622461
TI  - Reduced kidney lipoprotein lipase and renal tubule triglyceride accumulation in
      cisplatin-mediated acute kidney injury.
AB  - Peroxisome proliferator-activated receptor-alpha (PPARalpha) activation
      attenuates cisplatin (CP)-mediated acute kidney injury by increasing fatty acid
      oxidation, but mechanisms leading to reduced renal triglyceride (TG) accumulation
      could also contribute. Here, we investigated the effects of PPARalpha and CP on
      expression and enzyme activity of kidney lipoprotein lipase (LPL) as well as on
      expression of angiopoietin protein-like 4 (Angptl4), glycosylphosphatidylinositol
      anchored-HDL-binding protein (GPIHBP1), and lipase maturation factor 1 (Lmf1),
      which are recognized as important proteins that modulate LPL activity. CP caused
      a 40% reduction in epididymal white adipose tissue (WAT) mass, with a reduction
      of LPL expression and activity. CP also reduced kidney LPL expression and
      activity. Angptl4 mRNA levels were increased by ninefold in liver and kidney
      tissue and by twofold in adipose tissue of CP-treated mice. Western blots of two
      dimensional gel electrophoresis identified increased expression of a neutral pI
      Angptl4 protein in kidney tissue of CP-treated mice. Immunolocalization studies
      showed reduced staining of LPL and increased staining of Angptl4 primarily in
      proximal tubules of CP-treated mice. CP also increased TG accumulation in kidney
      tissue, which was ameliorated by PPARalpha ligand. In summary, a PPARalpha ligand
      ameliorates CP-mediated nephrotoxicity by increasing LPL activity via increased
      expression of GPHBP1 and Lmf1 and by reducing expression of Angptl4 protein in
      the proximal tubule.

PMID- 22622464
TI  - Acute saline expansion increases nephron filtration and distal flow rate but
      maintains tubuloglomerular feedback responsiveness: role of adenosine A(1)
      receptors.
AB  - Temporal adaptation of tubuloglomerular feedback (TGF) permits readjustment of
      the relationship of nephron filtration rate [single nephron glomerular filtration
      rate (SNGFR)] and early distal tubular flow rate (V(ED)) while maintaining TGF
      responsiveness. We used closed-loop assessment of TGF in hydropenia and after
      acute saline volume expansion (SE; 10% body wt over 1 h) to determine whether 1)
      temporal adaptation of TGF occurs, 2) adenosine A(1) receptors (A(1)R) mediate
      TGF responsiveness, and 3) inhibition of TGF affects SNGFR, V(ED), or urinary
      excretion under these conditions. SNGFR was evaluated in Fromter-Wistar rats by
      micropuncture in 1) early distal tubules (ambient flow at macula densa), 2)
      recollected from early distal tubules while 12 nl/min isotonic fluid was added to
      late proximal tubule (increased flow to macula densa), and 3) from proximal
      tubules of same nephrons (zero flow to macula densa). SE increased both ambient
      SNGFR and V(ED) compared with hydropenia, whereas TGF responsiveness (proximal
      distal difference in SNGFR, distal SNGFR response to adding fluid to proximal
      tubule) was maintained, demonstrating TGF adaptation. A(1)R blockade completely
      inhibited TGF responsiveness during SE and made V(ED) more susceptible to
      perturbation in proximal tubular flow, but did not alter ambient SNGFR or V(ED).
      Greater urinary excretion of fluid and Na(+) with A(1)R blockade may reflect
      additional effects on the distal nephron in hydropenia and SE. In conclusion,
      A(1)R-independent mechanisms adjust SNGFR and V(ED) to higher values after SE,
      which facilitates fluid and Na(+) excretion. Concurrently, TGF adapts and
      stabilizes early distal delivery at the new setpoint in an A(1)R-dependent
      mechanism.

PMID- 22622465
TI  - Prostaglandin E2 EP3 receptor regulates cyclooxygenase-2 expression in the
      kidney.
AB  - Cyclooxygenase-2 (COX-2) is constitutively expressed and highly regulated in the
      thick ascending limb (TAL). As COX-2 inhibitors (Coxibs) increase COX-2
      expression, we tested the hypothesis that a negative feedback mechanism involving
      PGE(2) EP3 receptors regulates COX-2 expression in the TAL. Sprague-Dawley rats
      were treated with a Coxib [celecoxib (20 mg.kg(-1).day(-1)) or rofecoxib (10
      mg.kg(-1).day(-1))], with or without sulprostone (20 MUg.kg(-1).day(-1)).
      Sulprostone was given using two protocols, namely, previous to Coxib treatment
      (prevention effect; Sulp7-Coxib5 group) and 5 days after initiation of Coxib
      treatment (regression effect; Coxib10-Sulp5 group). Immunohistochemical and
      morphometric analysis revealed that the stained area for COX-2-positive TAL cells
      (MUm(2)/field) increased in Coxib-treated rats (Sham: 412 +/- 56.3, Coxib: 794 +/
      153.3). The Coxib effect was inhibited when sulprostone was used in either the
      prevention (285 +/- 56.9) or regression (345 +/- 51.1) protocols. Western blot
      analysis revealed a 2.1 +/- 0.3-fold increase in COX-2 protein expression in the
      Coxib-treated group, an effect abolished by sulprostone using either the
      prevention (1.2 +/- 0.3-fold) or regression (0.6 +/- 0.4-fold vs. control, P <
      0.05) protocols. Similarly, the 6.4 +/- 0.6-fold increase in COX-2 mRNA abundance
      induced by Coxibs (P < 0.05) was inhibited by sulprostone; prevention: 0.9 +/-
      0.3-fold (P < 0.05) and regression: 0.6 +/- 0.1 (P < 0.05). Administration of a
      selective EP3 receptor antagonist, L-798106, also increased the area for COX-2
      stained cells, COX-2 mRNA accumulation, and protein expression in the TAL.
      Collectively, the data suggest that COX-2 levels are regulated by a novel
      negative feedback loop mediated by PGE(2) acting on its EP3 receptor in the TAL.

PMID- 22622466
TI  - IP3-mediated octopamine-induced synaptic enhancement of crayfish LG neurons.
AB  - The biogenic amines, octopamine and serotonin, modulate the synaptic activity of
      the lateral giant interneuron (LG) circuitry of the crayfish escape behavior.
      Bath application of both octopamine and serotonin enhances the synaptic responses
      of LG to sensory stimulation. We have shown previously (Araki et al. J
      Neurophysiol 94:2644-2652, 2005) that a serotonin-induced enhancement of the LG
      response was mediated by an increase in cAMP levels following activation of
      adenylate cyclase; however, octopamine acts independently. Here, we clarify how
      octopamine enhances the LG response during sensory stimulation using
      physiological and pharmacological analyses. When phospholipase C inhibitor U
      73122 was directly injected into the LG before biogenic amine application, it
      abolished the enhancing effect of octopamine on direct sensory input to the LG,
      but did not block indirect input via sensory interneurons or the effect of
      serotonin. Direct injection of IP(3), and its analogue adenophostin A, into the
      LG increased the synaptic response of the LG to sensory stimulation. Thus, IP(3)
      mediates octopamine-induced synaptic enhancement of the LG, but serotonin acts
      independently. These results indicate that both octopamine and serotonin enhance
      the synaptic responses of the LG to sensory stimulation, but that they activate
      two different signaling cascades in the LG.

PMID- 22622467
TI  - Structural coloration signals condition, parental investment, and circulating
      hormone levels in Eastern bluebirds (Sialia sialis).
AB  - Many of the brilliant plumage coloration displays of birds function as signals to
      conspecifics. One species in which the function of plumage ornaments has been
      assessed is the Eastern bluebird (Sialia sialis). Studies of a population
      breeding in Alabama (USA) have established that plumage ornaments signal quality,
      parental investment, and competitive ability in both sexes. Here we tested the
      additional hypotheses that (1) Eastern bluebird plumage ornamentation signals
      nest defense behavior in heterospecific competitive interactions and (2)
      individual variation in plumage ornamentation reflects underlying differences in
      circulating hormone levels. We also tested the potential for plumage ornaments to
      signal individual quality and parental investment in a population breeding in
      Oklahoma (USA). We found that Eastern bluebirds with more ornamented plumage are
      in better condition, initiate breeding earlier in the season, produce larger
      clutches, have higher circulating levels of the stress hormone corticosterone,
      and more ornamented males have lower circulating androgen levels. Plumage
      coloration was not related to nest defense behavior. Thus, plumage ornamentation
      may be used by both sexes to assess the physiological condition and parental
      investment of prospective mates. Experimental manipulations of circulating
      hormone levels during molt are needed to define the role of hormones in plumage
      ornamentation.

PMID- 22622469
TI  - Progression while receiving preoperative chemotherapy should not be an absolute
      contraindication to liver resection for colorectal metastases.
AB  - PURPOSE: Tumor progression while receiving neoadjuvant chemotherapy (PD) has been
      associated with poor outcome and is commonly considered a contraindication to
      liver resection (LR). This study aims to clarify in a large multicenter setting
      whether PD is always a contraindication to LR. METHODS: Data from the
      LiverMetSurvey international registry were analyzed. Patients undergoing LR for
      colorectal metastases without extrahepatic disease after neoadjuvant chemotherapy
      between 1990 and 2009 were reviewed. RESULTS: Among 2143 patients, PD occurred in
      176 (8.2 %). Risk of progression was increased after 5-FU or irinotecan (22.7 %
      vs. 6.8 % after other regimens, p < 0.0001; 14.9 % vs. 7.2 %, p < 0.0001), while
      it was reduced after oxaliplatin (5.6 % vs. 12.0 %, p < 0.0001) and still
      diminished among patients receiving targeted therapies (2.6 %). PD was an
      independent prognostic factor of survival at multivariate analysis (35 % vs. 49
      %, p = 0.0006). In the PD group, 3 independent prognostic factors were
      identified: carcinoembryonic antigen (CEA) >= 200 ng/mL (p = 0.003), >3
      metastases (p = 0.028), and tumor diameter >= 5 0 mm (p = 0.002). A survival
      predictive model showed that patients without any risk factors had 5-year
      survival rates of 53.3 %; good survival results were still observed if metastases
      were >3 or >= 50 mm (29.9 and 19.1 %, respectively). On the contrary, survival
      was less than 10 % at 3 years in the presence of >1 prognostic factor or CEA of
      >= 200 ng/mL. CONCLUSIONS: PD is a negative prognostic factor, but it is not an
      absolute contraindication to LR. Patients with PD could be scheduled for LR
      except for those with >3 metastases and >= 50 mm, or CEA >= 200 ng/mL in whom
      further chemotherapy is recommended.

PMID- 22622470
TI  - Lymph node dissection after chemoradiation in esophageal cancer: a subgroup
      analysis of patients with and without pathological response.
AB  - BACKGROUND: Extensive lymph node dissection (LND) is beneficial in primarily
      resected esophageal cancer patients. Such benefit was believed to be seen in
      neoadjuvant chemoradiotherapy (CRT)-treated patients, but evidence was
      inconsistent. We hypothesized that CRT might offset the benefit of LND in certain
      subgroup of patients, especially in major responders. METHODS: The clinical
      pathological data and survival of esophageal squamous cell carcinoma patients who
      received curative resection after CRT between 1996 and 2007 were analyzed. On the
      basis of the mean LND number of the cohort, patients were divided into two
      groups: group 1, lower LND, and group 2, higher LND. RESULTS: The cohort
      comprised 303 patients (295 men and 8 women) with a mean age of 55.4 years. There
      were 179 patients in group 1 and 124 patients in group 2. One hundred one
      patients had pathological complete response (pCR). There were more pCR in group 1
      (38 vs. 26.6%, P = 0.039) and more lymph node positive cases in group 2 (16 vs.
      27.4%, P = 0.018). Extent of LND had no survival difference in the entire cohort
      (overall survival 32 vs. 38%, P = 0.31). With the stratification analysis
      according to tumor response, inadequate LND exhibited negative impact in patients
      who did not experience pCR (P = 0.027). Without adequate LND, the survival of
      ypTxN0 was equally poor as ypN-positive cases (overall survival 15 vs. 16%, P =
      0.791). In the pCR group, the extent of LND had an impact on survival.
      CONCLUSIONS: The effect of LND was influenced by tumor response after CRT. There
      is a strong survival benefit for extensive LND after CRT in esophageal squamous
      cell carcinoma, especially in non-pCR patients.

PMID- 22622468
TI  - Soluble guanylate cyclase: a potential therapeutic target for heart failure.
AB  - The number of annual hospitalizations for heart failure (HF) and the mortality
      rates among patients hospitalized for HF remains unacceptably high. The search
      continues for safe and effective agents that improve outcomes when added to
      standard therapy. The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic
      guanosine monophosphate (cGMP) pathway serves an important physiologic role in
      both vascular and non-vascular tissues, including regulation of myocardial and
      renal function, and is disrupted in the setting of HF, leading to decreased
      protection against myocardial injury, ventricular remodeling, and the cardio
      renal syndrome. The impaired NO-sGC-cGMP pathway signaling in HF is secondary to
      reduced NO bioavailability and an alteration in the redox state of sGC, making it
      unresponsive to NO. Accordingly, increasing directly the activity of sGC is an
      attractive pharmacologic strategy. With the development of two novel classes of
      drugs, sGC stimulators and sGC activators, the hypothesis that restoration of NO
      sGC-cGMP signaling is beneficial in HF patients can now be tested.
      Characterization of these agents in pre-clinical and clinical studies has begun
      with investigations suggesting both hemodynamic effects and organ-protective
      properties independent of hemodynamic changes. The latter could prove valuable in
      long-term low-dose therapy in HF patients. This review will explain the role of
      the NO-sGC-cGMP pathway in HF pathophysiology and outcomes, data obtained with
      sGC stimulators and sGC activators in pre-clinical and clinical studies, and a
      plan for the further clinical development to study these agents as HF therapy.

PMID- 22622471
TI  - Low expression of IGFBP7 is associated with poor outcome of pancreatic ductal
      adenocarcinoma.
AB  - BACKGROUND: Insulin-like growth factor binding protein 7(IGFBP7) has been
      implicated as a potential tumor suppressor in various human cancers, although the
      role of IGFBP7 in pancreatic ductal adenocarcinoma (PDAC) is still unknown. We
      investigated the expression pattern and clinical significance of IGFBP7 in human
      PDAC. METHODS: IGFBP7 expression was evaluated by immunohistochemistry in 190
      patients with PDAC who underwent surgical tumor resection. Expression of IGFBP7
      was correlated with that of p53 and Ki-67, clinicopathologic features. We also
      evaluated overall survival (OS) according to expression of IGFBP7 by Kaplan-Meier
      and Cox regression analyses. RESULTS: IGFBP7 expression was significantly
      downregulated in pancreatic cancer tissues compared with adjacent normal pancreas
      (P < 0.001) and was inversely associated with Ki-67 expression (r = -0.284, P <
      0.001). No significant relationships were found for clinicopathologic features,
      such as diameter of tumor, node status, grade, and stage. Importantly, low
      expression of IGFBP7 was associated with poor OS, and this was also significant
      in multivariate Cox regression analysis (hazard ratio [HR], 1.38; 95 % confidence
      interval [95 % CI], 1.00-1.91; P = 0.05). CONCLUSIONS: We demonstrate for the
      first time that IGFBP7 is downregulated in pancreatic cancer, and low expression
      of IGFBP7 is correlated with increased proliferation and poor postoperative
      survival. IGFBP7 may be a tumor suppressor in PDAC.

PMID- 22622472
TI  - Size-based clinical response evaluation is insufficient to assess clinical
      response of sarcomas treated with isolated limb perfusion with TNF-alpha and
      melphalan.
AB  - BACKGROUND: The clinical assessment of the response of sarcomas to preoperative
      treatment is usually defined using size-based evaluation standards. For
      nonresectable sarcomas, hyperthermic isolated limb perfusion with TNF-alpha and
      melphalan (TM-ILP) yields high response rates. Based on our experience, we assume
      that anatomic radiological response criteria are insufficient to assess the
      degree of regression after TM-ILP. METHODS: The clinical response of 35 sarcomas
      to TM-ILP was assessed by unidimensional, bidimensional, and tridimensional size
      based anatomical criteria, and responders were identified according to the
      established thresholds. The same tumors were investigated for pathological
      response according to the Salzer-Kuntschik regression scale (>90% devitalization)
      and reviewed for cystic degeneration, hemorrhage, and predominant necrotic or
      fibrosclerotic regression phenotype. RESULTS: None of the clinical response
      criteria were able to reliably identify the pathologic responders. The extent of
      size changes showed no association with the pathological degree of regression.
      The number of clinical responders was low compared with the number of
      pathological responders (RECIST N = 1, WHO N = 3, volumetry N = 3, pathology N =
      19). The occurrence of hemorrhage and/or cystic degeneration was more frequently
      observed in predominant necrotic sarcomas and was associated with an increase in
      tumor size after TM-ILP. Furthermore, we identified the fibrosclerotic phenotype
      of regression to be more significantly strongly associated with posttherapeutic
      shrinkage than necrosis. CONCLUSIONS: Size-based clinical response evaluation is
      insufficient to assess clinical response in TM-ILP-treated sarcomas. The size
      changes of tumors after therapy reflect the type of regression rather than the
      extent of destruction.

PMID- 22622473
TI  - Biology, treatment, and outcome in very young and older women with DCIS.
AB  - BACKGROUND: This study examines a modern cohort of women with ductal carcinoma-in
      situ (DCIS) in order to identify potential differences in clinical presentation,
      treatments, and outcome based on age. METHODS: From 1996 to 2009, a total of 2037
      patients with pure DCIS were treated. Clinical presentation, pathologic factors,
      type of surgery and adjuvant therapy, and local recurrence rates among age groups
      were compared and analyzed. Median follow-up was 5.2 years. RESULTS: There were
      132 patients (6.5 %) aged <40, 1,690 (83 %) aged 40-70, and 215 (10.5 %) aged
      >70. Younger patients (<40) were significantly more likely to have a family
      history of breast cancer, present with clinical symptoms, undergo mastectomy with
      immediate reconstruction, and have a contralateral prophylactic mastectomy (P <
      0.05). Older patients (>70) were significantly less likely to use adjuvant
      radiotherapy and tamoxifen (P < 0.05). No significant differences were found in
      DCIS size, estrogen receptor status, necrosis, or contralateral breast cancer
      based on age. Among women <40, 29.3 % had evidence of multicentric disease versus
      17.7 and 13.3 % in the women aged 40-70 and those >70, respectively (P = 0.004).
      On multivariate analysis, younger age (<40), larger-size DCIS (>=1.5 cm), and no
      use of radiotherapy were significant independent predictors of locoregional
      recurrence. The 5 year rates of local recurrence were 10.1 % in women <40
      compared with 3.2 % in older women (P = 0.005). CONCLUSIONS: Younger patients
      with DCIS more often have multicentric disease, present with clinical findings,
      and opt for or require mastectomy with immediate reconstruction. Conservative
      surgery is only appropriate for younger patients if adjuvant radiotherapy is
      delivered.

PMID- 22622474
TI  - Elevated levels of proliferating and recently migrated tumor-associated
      macrophages confer increased aggressiveness and worse outcomes in breast cancer.
AB  - PURPOSE: Macrophages play a major role in inflammatory processes and have been
      associated with poor prognosis in a variety of cancers, including breast cancer.
      Previously, we investigated the relationship of a subset of tumor-associated
      macrophages (PCNA(+) TAMs) with clinicopathologic characteristics of breast
      cancer. We reported that high PCNA(+) TAM counts were associated with hormone
      receptor (HR)-negative, high-grade tumors and early recurrence. To further
      understand the significance of elevated PCNA(+) TAMs and the functionality of
      TAMs, we examined the expression of S100A8/S100A9 with the antibody Mac387. The
      heterodimeric S100A8/S100A9 complex plays a role in inflammation and is increased
      in several cancer types. METHODS: We performed immunohistochemistry using the
      Mac387 antibody on 367 invasive human breast cancer cases. Results were compared
      to previous PCNA(+) TAM counts and were correlated with patient outcomes
      adjusting for HR status and histologic grade. RESULTS: Like PCNA(+) TAMs, high
      Mac387 counts were associated with HR negativity, high tumor grade, younger age,
      and decreased recurrence-free survival. Mac387, however, appears to identify both
      a subset of macrophages and a subset of tumor cells. The concordance between
      Mac387 and PCNA(+) TAM counts was low and cases that had both high Mac387 and
      high PCNA(+) TAMs counts had a stronger association with early recurrence.
      CONCLUSIONS: The presence of high numbers of PCNA(+) TAMs and Mac387-positive
      cells in breast cancers with poor outcomes may implicate a subset of TAMs in
      breast cancer pathogenesis, and may ultimately serve to develop potential
      cellular targets for therapeutic interventions.

PMID- 22622475
TI  - Evidences of efficacy of allergen immunotherapy in atopic dermatitis:  an updated
      review.
AB  - PURPOSE OF REVIEW: To update and assess the quality of the evidence concerning
      the efficacy of allergen immunotherapy for atopic eczema. Desensitization for
      eczema as a clinical manifestation of food allergy was not a target of this
      review. RECENT FINDINGS: In the past 5 years, from the last comprehensive
      systematic review of Bussmann et al., four controlled trials have been published
      on this topic, two using injection and two sublingual immunotherapy. The active
      treatment was compared with placebo, pharmacotherapy or different schedules of
      immunotherapy. The studies variably involved adults and children and showed an
      improvement of atopic dermatitis severity. Severe eczema seems less responsive to
      hyposensitization, and a minimal treatment duration of 9-12 months appears
      necessary. SUMMARY: The efficacy of immunotherapy in patients with atopic eczema
      has been poorly investigated in the past 5 years. The available trials have small
      dimension and some methodological shortcomings, in addition to incomplete
      reporting. Clinical and methodological interstudy heterogeneity is apparent. Only
      one study adopted a placebo control. The evidence of efficacy has not critically
      changed from previous systematic observations. No long-term studies have been
      conducted to determine the disease-modifying potential of specific immunotherapy
      in the context of the 'allergy march'.

PMID- 22622476
TI  - Update on systemic therapies for atopic dermatitis.
AB  - PURPOSE OF REVIEW: Although many atopic dermatitis patients can be treated
      satisfactorily with topical medications and systemic anti-itch approaches, a
      smaller subset require more aggressive systemic therapies. Familiarity with the
      latest literature on the benefits and risks of these treatments will enable the
      clinician and patient to select the most appropriate therapy based on the
      patient's lifestyle, assessments of risks and comorbidities. RECENT FINDINGS:
      Additional data have come to light altering the risk and benefit ratio of certain
      systemic atopic dermatitis therapies. In 2011, we saw several head-to-head,
      randomized controlled trials of established systemic medications for the
      treatment of atopic dermatitis. A few new systemic atopic dermatitis treatments
      have highlighted how targeted therapies may inform us about disease pathogenesis.
      SUMMARY: In light of the risk of hepatosplenic T-cell lymphomas, a greater degree
      of caution is warranted in the use of azathioprine. NBUVB, mycophenolate, and
      methotrexate remain the reasonable first-line systemic treatment options for
      atopic dermatitis. A brief run-in with high-dose cyclosporine to clear atopic
      dermatitis followed by maintenance with low-dose cyclosporine or cellcept - both
      of which have better risk and benefit ratios is a reasonable approach. Interferon
      gamma and intravenous immunoglobulin, although expensive, are potential options,
      and possibly most ideal for atopic dermatitis patients plagued by significant
      viral skin infections such as eczema herpeticum. A better understanding of the
      immunopathogenesis of atopic dermatitis will come with the exploration of novel
      targeted therapies.

PMID- 22622477
TI  - The added value of allergen microarray technique to the management of poly
      sensitized allergic patients.
AB  - PURPOSE OF REVIEW: To evaluate the relevance of results obtained using allergen
      microarray technique for the description of the IgE repertoire in allergic
      patients. RECENT FINDINGS: Allergen microarray was introduced at the beginning of
      the last decade. Since then, an increasing number of allergens have been
      identified, correspondingly increasing the accuracy of the description of
      immunoglobulin (Ig)E repertoire. In the last 2 years, a large number of articles
      were published that accurately described not only the general features of this
      technique, but also the use of allergen microarray in specific situations.
      SUMMARY: The recent availability of highly purified or recombinant allergen
      components has deeply modified the laboratory approach to allergy diagnosis that,
      now, it cannot be limited to the detection of IgE specific to extractive
      allergens. Indeed, these contain both specific components (i.e. molecules
      strictly associated to that allergen source) and pan-allergen or cross-reacting
      allergens (i.e. molecules that are present in different similar allergen sources
      or that are present in highly homologous structures in different species). Newer
      techniques such as recombinant allergen testing and allergen microarray allow a
      more detailed evaluation of IgE responses. Future research is needed to more
      clearly define their role in clinical practice.

PMID- 22622479
TI  - Postanesthesia care unit imaging is unnecessary when intraoperative imaging is
      used during anterior cervical decompression and fusion procedures.
AB  - STUDY DESIGN: Retrospective case series. OBJECTIVE: To characterize the clinical
      utility of imaging in the postanesthesia care unit (PACU) after anterior cervical
      decompression and fusion (ACDF) procedures. SUMMARY OF BACKGROUND DATA: Two sets
      of imaging are often taken at the end of ACDF procedures: one intraoperatively
      and the other in the PACU. The latter may have low clinical utility. MATERIALS
      AND METHODS: One hundred four patients who underwent ACDF procedures with
      anterior plate/screw constructs were identified. A panel assessed intraoperative
      and PACU series for adequacy of images to detect potential issues with placement
      of the surgical construct and for any actual visible issues with placement of the
      surgical construct. RESULTS: Intraoperative series were adequate to detect
      potential issues with construct placement for 78.8% of cases, whereas PACU series
      were adequate for only 58.7% of cases (significant difference, P<0.001). For both
      series, nearly all inadequacies were because of the shoulders obstructing the
      lateral view. Accordingly, cases with lower inferior operative levels were much
      more likely to have inadequate intraoperative and PACU series than cases with
      higher inferior operative levels (significant differences, P<0.001 for both). In
      no case was an issue with construct placement visible on a PACU series that was
      not also visible on an intraoperative series. CONCLUSIONS: This study
      demonstrates that PACU images are inferior to intraoperative images and offer
      little or no incremental clinical utility for detecting issues with surgical
      construct placement after ACDF procedures. PACU imaging after ACDF procedures
      might be discontinued to realize savings in time, cost, and radiation exposure.

PMID- 22622478
TI  - Depression and cognitive impairment in older adults.
AB  - Late life depression (LLD) is a heterogeneous illness with high rates of
      treatment resistance. Cognitive impairment is common in the context of LLD, and
      LLD may be a prodromal symptom and/or potentially a risk factor for dementia.
      This manuscript reviews the most recent research into the cognitive deficits
      associated with LLD and risk of conversion to dementia in the context of LLD. We
      discuss potential moderators and mediators of cognitive deficits in LLD,
      including demographic and clinical variables, in addition to brain structure and
      function. Potential interventions for cognitive symptoms of LLD are reviewed. We
      conclude with a discussion of the broader implications of what is now known about
      LLD, and how this might be applied toward improved prognosis and models for
      effective treatment.

PMID- 22622480
TI  - [Thrombocytopenia in Graves' disease].
AB  - HISTORY AND ADMISSION FINDINGS: We report on a patient with relapse of Graves'
      disease and immune thrombocytopenia (ITP). In the light of thrombocytopenia,
      thyroidectomy could not be performed. INVESTIGATIONS: Cytologic examinations of
      the peripheral blood count showed a distinctive thrombocytopenia and giant
      platelets. In the bone marrow smear, a huge amount of megacaryocytes was seen.
      Examinations including platelet antibodies, virology studies, helicobacter
      pylori, and whole body computed tomography showed no pathological results.
      DIAGNOSIS, TREATMENT UND COURSE: The results were interpreted as ITP. The patient
      received an intervall of two month several cycles of glucocorticoid treatment and
      immunglobulines. There was no significant improvement after this therapy. As
      second-line treatment the patient received rituximab, with no change in the
      platelet count. In contrast, treatment with a thrombopoietin-receptor-agonist was
      successful. Finally, normalisation of thyroid function was associated with a
      normalisation of the platelet count also after discontinuation of ITP treatment.
      CONCLUSION: In recent studies, thrombopoetin-receptor-agonists were established
      for the treatment of recurrent or refractory ITP. In our case, successful
      management of Graves' disease including efficient thyreostatic therapy may also
      have contributed to normalisation of the platelet count. Splenectomy should be
      deferred in these patients.

PMID- 22622481
TI  - Highly efficient visible-light-driven photocatalytic activities in synthetic
      ordered monoclinic BiVO4 quantum tubes-graphene nanocomposites.
AB  - Photocatalytic purification of polluted water is a very promising way to
      alleviate the increasingly serious water resources crisis. Despite tremendous
      efforts, developing visible-light-driven photocatalysts with high activity at low
      cost still remains a great challenge. Herein, we report for the first time the
      design and synthesis of ordered m-BiVO(4) quantum tubes-graphene nanocomposites
      that exhibit unprecedented visible-light-driven photocatalytic activities, over
      20 times faster than that of commercial P25 or bulk BiVO(4) and roughly 1.5 times
      more active than that of bare m-BiVO(4) quantum tubes. Notably, the unusual
      photoreactivities arise from the synergistic effects between the microscopic
      crystal structure of m-BiVO(4) and macroscopic morphological features of ordered
      m-BiVO(4) quantum tubes and two-dimensional graphene sheets. These structural
      features help to provide increased photocatalytic reaction sites, extended
      photoresponding range, enhanced charge transportation and separation efficiency
      simultaneously. Briefly, this work not only provides a simple and straightforward
      strategy for fabricating highly efficient and stable graphene-based
      nanocomposites, but also proves that these unique structures are excellent
      platforms for significantly improving their visible-light-driven photoactivities,
      holding great promise for their applications in the field of purifying polluted
      water resources.

PMID- 22622482
TI  - Abortion policy and science: can controversy and evidence co-exist?
AB  - Abortion policies should be based on evidence. Over the past four decades in the
      United States, we have accumulated more data about the practice of legal abortion
      than any other surgical procedure. This evidence has documented the public health
      impact of increased access to safer abortion. In recent years, state laws to
      restrict abortion access have gained momentum. An accompanying article in this
      issue of JPHP uses extant data to examine whether two restrictive policies have
      had a measurable effect on abortion morbidity. The analysis found an unexpected
      result - states which imposed restrictions had lower levels of abortion
      complications than those who did not. Various explanations exist for these
      findings. Caution is needed to interpret observational findings, especially with
      polarizing issuess like abortion.

PMID- 22622483
TI  - Legal restrictions and complications of abortion: insights from data on
      complication rates in the United States.
AB  - Although US federal law requires all American states to permit abortion within
      their borders, states retain authority to impose restrictions.We used hospital
      discharge data to study the rates of major abortion complications in 23 states
      from 2001 to 2008 and their relationship to two laws: (i) restrictions on
      Medicaid - the state insurance programs for the poor - funding, and (ii)
      mandatory delays before abortion. Of 131 000 000 discharges in the data set, 10
      980 involved an abortion complication. The national rate for complications was
      1.90 per 1000 abortions (95 per cent CI: 1.57-2.23). Eleven states required
      mandatory delays and 12 restricted funding for Medicaid participants. After
      controlling for socioeconomic characteristics and the pregnancy complication
      rate, legal restrictions were associated with lower complication rates: mandatory
      delays (OR 0.79(0.65-0.95)) and restricted Medicaid funding (OR 0.74 (0.61
      0.90)). This result may reflect the fact that states without restrictions perform
      a higher percentage of second-trimester abortions. This study is the first to
      assess the association between legal restrictions on abortion and complication
      rates.

PMID- 22622484
TI  - Retinoblastoma in the perinatal and neonatal child.
AB  - Retinoblastoma is a rare primary intraocular malignancy. Presentation in the
      neonatal period is not common. With improved genetic testing, screening of the
      unborn child and neonate is taking on a greater role in the management of these
      patients. Treatment of retinoblastoma in the neonate is complex and requires a
      multidisciplinary and highly individualized approach. If possible, focal
      modalities should be used and external beam radiation avoided. Systemic
      intravenous chemotherapy may be necessary with regimens including carboplatin,
      vincristine and etoposide. Such cases are best managed by specialist centers with
      access to experts in oncology, ophthalmology, radiation therapy, genetics,
      pathology and anesthesia.

PMID- 22622485
TI  - The alkenyl migration mechanism catalyzed by extradiol dioxygenases: a hybrid DFT
      study.
AB  - 6-Hydroxymethyl-6-methylcyclohexa-2,4-dienone is a mechanistic probe which when
      incubated with an extradiol dioxygenase yields a 2-tropolone product. This
      observation was originally interpreted as evidence supporting a direct
      heterolytic 1,2-alkenyl migration mechanism for a ring expansion reaction
      catalyzed by this class of Fe(II)-dependent nonheme enzymes (Xin and Bugg in J Am
      Chem Soc 130:10422-10430, 2008). In the work reported in this contribution we
      used quantum chemical methods to test whether such a mechanism is energetically
      possible and we found that it is not, neither for the mechanistic probe nor for
      the native catalytic cycle intermediate. Models of increasing complexity were
      used to calculate energy barriers to the heterolytic 1,2-alkenyl migration and
      alternative radical mechanisms. It was found that the former involves
      substantially higher barriers than the latter. A tentative radical mechanism that
      accounts for the transformation of the probe substrate to 2-tropolone was also
      proposed, and it involves acceptable barriers.

PMID- 22622486
TI  - Predictive value of the physiological deadspace/tidal volume ratio in the weaning
      process of mechanical ventilation in children.
AB  - OBJECTIVE: To evaluate the physiological deadspace/tidal volume ratio (VD/VT) as
      a predictor of extubation failure in 42 ventilated children (median age: 4.75
      years). METHOD: Extubation readiness was determined using the criteria proposed
      by the 6th International Consensus Conference on Intensive Care Medicine adapted
      to children. RESULTS: Non-invasive ventilation (NIV) was used in four patients
      who developed respiratory failure after extubation; none was reintubated.
      Children who needed NIV to avoid reintubation had a significantly higher VD/VT
      ratio than those who were extubated without NIV (p < 0.001). The cut-off value of
      VD/VT ratio was 0.55 and the area under the receiver operating characteristic
      curve was 0.86. CONCLUSION: Our findings confirm the good predictive value of
      weaning success/failure of the VD/VT ratio and suggest its role for predicting
      the need for NIV after extubation.

PMID- 22622487
TI  - [Transurethral en bloc resection of non-muscle invasive bladder cancer. What is
      the state of the art?].
AB  - Bladder cancer of the urothelium is the second most common malignancy among
      urological tumors. In view of a worldwide aging population and the fact that
      increased incidence rates are associated with higher age, new socioeconomic
      challenges will appear. Even nowadays the treatment of bladder cancer bears the
      highest lifetime treatment costs per patient among all forms of cancer. In
      conjunction with higher comorbidity rates among older patients urologists are
      facing new challenges in the treatment and care of patients with bladder cancer.
      The standard treatment for non-muscle invasive bladder cancer (NMIBC) is
      monopolar transurethral resection using resection loops (TURB). Based on
      experience in the surgical treatment of benign prostatic hyperplasia, different
      concepts of en bloc resection of bladder tumors using alternative energy
      resources (e.g. holmium laser, thulium laser and the water-jet HybridKnife) have
      been developed. Goals of new treatment modalities are reduction of perioperative
      and postoperative comorbidities, better pathological work-up of the specimens and
      increased recurrence-free survival. Postulated advantages using laser devices are
      a more precise cutting line as well as better hemostasis. The evidential value of
      this review is limited due to the lack of randomized, prospective studies.
      However, there is a tendency towards a limitation of perioperative and
      postoperative morbidities as well as higher chance of well-preserved tissues for
      better pathohistological evaluation using en bloc resection methods. More studies
      with long-term follow-up periods and better randomization are needed to clarify
      whether en bloc strategies provide better long-term oncological survival.

PMID- 22622488
TI  - Breakthrough pain in patients referred to pain clinics: the Italian pain network
      retrospective study.
AB  - INTRODUCTION: Despite breakthrough pain (BTP) being one of the most severe forms
      of pain, there are no definitive data on its prevalence. METHODS: The authors
      performed a retrospective survey of the prevalence of BTP in consecutive patients
      in four Italian pain clinics, subsequent to application of an Italian law
      mandating detailed clinical records on pain characteristics, treatment, and
      results. Mean pain intensity was assessed with a numerical rating scale from 0 to
      10. RESULTS: The authors analyzed records of 1,401 patients (58% women, 33.1%
      patients with cancer). Transient episodes of severe pain or BTP were referred by
      790 patients (56.4%), including 58.2% of the men (342 of 588) and 55.1% of the
      women (448 of 813). Among the 464 patients with cancer, 70.3% reported daily
      exacerbation of pain. The mean BTP intensity was 8.31 +/- 1.58 and 31.1% of
      patients reported experiencing three episodes per day. CONCLUSION: Despite some
      limitations of the study, the authors show that transient episodes of severe pain
      or BTP are significantly present both in cancer and other diseases, and that many
      patients are not yet receiving appropriate opioid therapy. The authors need
      validated tools at international level for the diagnosis and treatment of BTP in
      patients with cancer and for transitory and patients with severe non-cancer pain.
      A survey at national level is needed to estimate the prevalence of BTP in
      different settings, to plan specific medical education.

PMID- 22622489
TI  - Unique magnetic properties and magnetization reversal process of CoFe2O4
      nanotubes fabricated by electrospinning.
AB  - CoFe(2)O(4) nanotubes have been directly fabricated by single-capillary spinneret
      electrospinning. The external diameter of the CoFe(2)O(4) nanotubes ranges from
      60 nm to 160 nm. The morphology and structure characterizations show that
      individual CoFe(2)O(4) nanotubes are made of CoFe(2)O(4) nanocrystals stacking
      along the nanotubes with no preferred growth directions and these individual
      nanocrystals are single crystal with a cubic spinel structure. Each nanocrystal
      was shown to be a single magnetic domain. The magnetic measurements show that the
      coercivity (H(c)) of the CoFe(2)O(4) nanotubes decreases from 10 400 Oe at 5 K to
      300 Oe at 360 K. The CoFe(2)O(4) nanotubes have a spin reorientation (SR) at 5 K,
      which is different from CoFe(2)O(4) nanorods and nanoparticles. Based on the
      observed morphology and crystal structure, a micromagnetic model, "chain-of
      rings", is developed to interpret the magnetic behavior of the CoFe(2)O(4)
      nanotubes. The theoretical coercivity (534 Oe) is in good agreement with the
      experimental results (509 Oe). It is believed that our work should open a new
      route to prepare various magnetic ferrite nanotubes and is significant for
      expanding the application of CoFe(2)O(4) into the new fields.

PMID- 22622490
TI  - Memory in early onset bipolar disorder and attention-deficit/hyperactivity
      disorder: similarities and differences.
AB  - Differentiating between early-onset bipolar disorder (BD) and attention
      deficit/hyperactivity disorder (ADHD) can be difficult. Memory problems are
      commonly reported in BD, and forgetfulness is among the diagnostic criteria for
      ADHD. We compared children and adolescents with BD (n = 23), ADHD combined type
      (ADHD-C; n = 26), BD + ADHD-C (n = 15), and 68 healthy controls on memory tests
      (Digit span, Children's Verbal Learning Test-II). Further analyses were performed
      on subgroups of BD (BD-I, BD-II/BD-NOS, with and without previous psychotic
      symptoms). All clinical groups demonstrated some problems with free recall, but
      the BD subgroup with a history of psychotic symptoms had a more pervasive problem
      that also included recognition and semantic clustering. The ADHD-C groups
      demonstrated the lowest performance on working memory. These data suggest that
      children and adolescents with BD and previously psychotic symptoms may have
      inefficient encoding of verbal material, whereas memory problems in ADHD-C appear
      more characterized by impaired free recall.

PMID- 22622491
TI  - Gels of shape-persistent macrocycles: the role of the interior.
AB  - The aggregation of shape-persistent macrocycles with an empty cavity, an
      undecyldiether strand and a tetraethylene glycol strand leads in all cases to a
      macroscopic gelation of the solvent. However, the gelation temperatures are fine
      tuned by the intraannular substituents.

PMID- 22622493
TI  - The early decline in renal function in patients with type 1 diabetes and
      proteinuria predicts the risk of end-stage renal disease.
AB  - The risk of end-stage renal disease (ESRD) remains high in patients with type 1
      diabetes and proteinuria; however, little is known about the rate of decline in
      their renal function. To help determine this, we enrolled patients with type 1
      diabetes and proteinuria whose estimated glomerular filtration rate (eGFR) was
      normal (equal to or above 60 ml/min per 1.73 m(2)). Using a minimum of five
      serial measurements of serum creatinine for 161 patients, we determined
      individual trajectories of eGFR change and the occurrence of ESRD during 5-18
      years of follow-up. The rates were linear for 110 patients, for 24 the nonlinear
      rate was mild enough to satisfy a linear model, and the rates were clearly
      nonlinear for only 27 patients. Overall, in more than one-third of patients, the
      eGFR decline was less than 3.5 ml/min per 1.73 m(2) per year and the lifetime
      risk of ESRD could be considered negligible. In the remainder of patients, eGFR
      declined with widely different slopes and ESRD developed within 2 to 18 years.
      Based on up to 5 years observation, when renal function was within the normal
      range, the estimates of early eGFR slope predicted the risk of ESRD during
      subsequent follow-up better than the baseline clinical characteristics of
      glycated hemoglobin, blood pressure, or the albumin to creatinine ratio. Thus,
      the early slope of eGFR decline in patients with type 1 diabetes and proteinuria
      can be used to predict the risk of ESRD.

PMID- 22622492
TI  - Update on fibroblast growth factor 23 in chronic kidney disease.
AB  - Chronic kidney disease (CKD) is a public health epidemic that affects millions of
      people worldwide. Presence of CKD predisposes individuals to high risks of end
      stage renal disease (ESRD), cardiovascular disease, and premature death.
      Disordered phosphate homeostasis with elevated circulating levels of fibroblast
      growth factor 23 (FGF23) is an early and pervasive complication of CKD. CKD is
      likely the most common cause of chronically elevated FGF23 levels, and the
      clinical condition in which levels are most markedly elevated. Although increases
      in FGF23 levels help maintain serum phosphate in the normal range in CKD,
      prospective studies in populations of pre-dialysis CKD, incident and prevalent
      ESRD, and kidney transplant recipients demonstrate that elevated FGF23 levels are
      independently associated with progression of CKD and development of
      cardiovascular events and mortality. It was originally thought that these
      observations were driven by elevated FGF23 levels acting as a highly sensitive
      biomarker of toxicity due to phosphate. However, FGF23 itself has now been shown
      to mediate 'off-target,' direct, end-organ toxicity in the heart, which suggests
      that elevated FGF23 levels may be a novel mechanism of adverse outcomes in CKD.
      This report reviews recent advances in FGF23 biology relevant to CKD, the
      classical effects of FGF23 on mineral homeostasis, and the studies that
      established FGF23 excess as a biomarker and novel mechanism of cardiovascular
      disease. The report concludes with a critical review of the effects of different
      therapeutic strategies targeting FGF23 reduction and how these might be leveraged
      in a future randomized trial aimed at improving outcomes in CKD.

PMID- 22622494
TI  - Aldosterone deficiency and mineralocorticoid receptor antagonism prevent
      angiotensin II-induced cardiac, renal, and vascular injury.
AB  - Angiotensin II causes cardiovascular injury in part by aldosterone-induced
      mineralocorticoid receptor activation, and it can also activate the
      mineralocorticoid receptor in the absence of aldosterone in vitro. Here we tested
      whether endogenous aldosterone contributes to angiotensin II/salt-induced
      cardiac, vascular, and renal injury by the mineralocorticoid receptor.
      Aldosterone synthase knockout mice and wild-type littermates were treated with
      angiotensin II or vehicle plus the mineralocorticoid receptor antagonist
      spironolactone or regular diet while drinking 0.9% saline. Angiotensin II/salt
      caused hypertension in both the knockout and wild-type mice, an effect
      significantly blunted in the knockout mice. Either genetic aldosterone deficiency
      or mineralocorticoid receptor antagonism reduced cardiac hypertrophy, aortic
      remodeling, and albuminuria, as well as cardiac, aortic, and renal plasminogen
      activator inhibitor-1 mRNA expression during angiotensin II treatment.
      Mineralocorticoid receptor antagonism reduced angiotensin II/salt-induced
      glomerular hypertrophy, but aldosterone deficiency did not. Combined
      mineralocorticoid receptor antagonism and aldosterone deficiency reduced blood
      urea nitrogen and restored nephrin immunoreactivity. Angiotensin II/salt also
      promoted glomerular injury through the mineralocorticoid receptor in the absence
      of aldosterone. Thus, mineralocorticoid antagonism may have protective effects in
      the kidney beyond aldosterone synthase inhibition.

PMID- 22622495
TI  - The effect of increasing age on the prognosis of non-dialysis patients with
      chronic kidney disease receiving stable nephrology care.
AB  - To define whether age modifies the prognosis of patients with chronic kidney
      disease (CKD) on nephrology care, we prospectively followed patients with CKD who
      have been receiving nephrology care in a clinic for 1 year or more. The incidence
      of end-stage renal disease (ESRD), defined by the occurrence of dialysis or
      transplant, or death without ESRD was estimated by a competing-risk approach, and
      interactions between age and risk factors tested in Cox models over a median
      follow-up period of 62.4 months. Of 1248 patients with stage III-V CKD, 481 were
      younger than 65, 410 were between 65 and 75, and 357 were over 75 years old.
      Within each age class, the mean estimated glomerular filtration rate(eGFR) was
      31, 32, and 29 ml/min per 1.73 m2, respectively. There were 394 ESRD events and
      353 deaths. The risk of ESRD was higher than the risk of death without ESRD for
      ages <60 years, and independent of eGFR. The ESRD risk diminished with aging but
      still prevailed for eGFRs of 25-35 in patients between 65 and 75 years and with
      an eGFR below 15 in those up to 85 years old. Proteinuria significantly increased
      the risk of ESRD with advancing age. Surprisingly, the unfavorable effects of
      cardiovascular disease on ESRD and of diabetes on survival significantly
      decreased with increasing age. Male gender, higher phosphate, lower body mass
      index, and hemoglobin were age-independent predictors for ESRD, while
      cardiovascular disease, lower hemoglobin, higher proteinuria and uric acid, and
      ESRD also predicted death. Thus, in older patients on nephrology care, the risk
      of ESRD prevailed overmortality even when eGFR was not severely impaired.
      Proteinuria increases ESRD risk, while the predictive role of other modifiable
      risk factors was unchanged compared with younger patients.

PMID- 22622497
TI  - At-home short daily hemodialysis improves the long-term health-related quality of
      life.
AB  - Patients with chronic kidney disease treated by in-center conventional
      hemodialysis (3 times per week) have significant impairments in health-related
      quality of life measures, which have been associated with increased morbidity and
      mortality. FREEDOM is an ongoing prospective cohort study measuring the potential
      benefits of at-home short daily (6 times per week) hemodialysis. In this interim
      report we examine the long-term effect of short daily hemodialysis on health
      related quality of life, as measured by the SF-36 health survey. This was
      administered at baseline, 4 and 12 months after initiation of short daily
      hemodialysis to 291 participants (total cohort), of which 154 completed the 12
      month follow-up (as-treated cohort). At the time of analysis, the mean age was 53
      years, 66% were men, 58% had an AV fistula, 90% transitioned from in-center
      hemodialysis, and 45% had diabetes mellitus. In the total cohort analysis, both
      the physical- and mental-component summary scores improved over the 12-month
      period, as did all 8 individual domains of the SF-36. The as-treated cohort
      analysis showed similar improvements with the exception of the role-emotional
      domain. Significantly, in the as-treated cohort, the percentage of patients
      achieving a physical-component summary score at least equivalent to the general
      population more than doubled. Hence, at-home short daily hemodialysis is
      associated with long-term improvements in various physical and mental health
      related quality of life measures.

PMID- 22622496
TI  - Improved equations estimating GFR in children with chronic kidney disease using
      an immunonephelometric determination of cystatin C.
AB  - The Chronic Kidney Disease in Children study is a cohort of about 600 children
      with chronic kidney disease (CKD) in the United States and Canada. The
      independent variable for our observations was a measurement of glomerular
      filtration rate(GFR) by iohexol disappearance (iGFR) at the first two visits 1
      year apart and during alternate years thereafter. In a previous report, we had
      developed GFR estimating equations utilizing serum creatinine, blood urea
      nitrogen, height, gender, and cystatin C measured by an immunoturbidimetric
      method; however, the correlation coefficient of cystatin C and GFR(0.69) was less
      robust than expected. Therefore, 495 samples were re-assayed using
      immunonephelometry. The reciprocal of immunonephelometric cystatin C was as well
      correlated with iGFR as was height/serum creatinine (both 0.88). We developed a
      new GFR estimating equation using a random 2/3 of 965 person-visits and applied
      it to the remaining 1/3 as a validation data set. In the validation dataset, the
      correlation of the estimated GFR with iGFR was 0.92 with high precision and no
      bias; 91 and 45% of eGFR values were within 30 and 10% of iGFR, respectively.
      This equation works well in children with CKD in a range of GFR from 15 to 75
      ml/min per 1.73 m2. Further studies are needed to establish the applicability to
      children of normal stature and muscle mass, and higher GFR.

PMID- 22622498
TI  - The receptor of advanced glycation end products plays a central role in advanced
      oxidation protein products-induced podocyte apoptosis.
AB  - The accumulation of plasma advanced oxidation protein products (AOPPs) is
      prevalent in chronic kidney disease. We previously showed that accumulation of
      AOPPs resulted in podocyte apoptosis and their deletion by a cascade of signaling
      events coupled with intracellular oxidative stress. The transmembrane receptor
      that specifically transmits the AOPPs' signals to elicit cellular activity,
      however, remains unknown. Using co-immunoprecipitation and immunofluorescence, we
      found that AOPPs colocalized and interacted with the receptor of advanced
      glycation end products (RAGE) on podocytes. Blocking RAGE by anti-RAGE
      immunoglobulin G or its silencing by siRNA significantly protected podocytes from
      AOPPs-induced apoptosis both in vitro and in vivo and ameliorated albuminuria in
      AOPPs-challenged mice. AOPPs-induced activation of nicotinamide adenine
      dinucleotide phosphate oxidase and the excessive generation of intracellular
      superoxide were largely inhibited by anti-RAGE immunoglobulin G or RAGE siRNA.
      Moreover, blockade of RAGE decreased the activation of the p53/Bax/caspase
      dependent proapoptotic pathway induced by AOPPs. Thus, AOPPs interact with RAGE
      to induce podocyte apoptosis and this, in part, may contribute to the progression
      of chronic kidney disease.

PMID- 22622499
TI  - Early initiation of peritoneal dialysis in neonates and infants with acute kidney
      injury following cardiac surgery is associated with a significant decrease in
      mortality.
AB  - Association between early renal replacement therapy and better survival has been
      reported in adults with postoperative kidney injury, but not in children
      undergoing cardiac surgery. We conducted a retrospective cohort study of 146
      neonates and infants requiring peritoneal dialysis following cardiac surgery in a
      tertiary referral hospital. A propensity score was used to limit selection bias
      due to timing of dialysis, and included baseline and intraoperative
      characteristics, requirement for postoperative extracorporeal membrane
      oxygenation, and creatinine clearance variation. Inverse probability of treatment
      weighting resulted in good balance between groups for all baseline and
      intraoperative variables. After weighting, 30-day and 90-day mortality were
      compared between the 109 patients placed on dialysis early, within the first day
      of surgery, and those with delayed dialysis, commencing on the second day of
      surgery or later, using logistic regression and survival analysis. Mortality was
      28.1% at 30 days, and was 36.3% during follow-up. Early dialysis was associated
      with a 46.7% decrease in the 30-day and a 43.5% decrease in the 90-day mortality
      rate when compared with delayed dialysis. All other short-term outcome variables
      were similar. Thus, initiation of peritoneal dialysis on the day of or the first
      day following surgery was associated with a significant decrease in mortality in
      neonates and infants with acute kidney injury.

PMID- 22622500
TI  - The serum anion gap is altered in early kidney disease and associates with
      mortality.
AB  - It is well known that uremia causes an increase in the serum anion gap (AG);
      however, whether changes in the AG occur earlier in the course of chronic kidney
      disease is not known. Here we investigated whether different measures of the AG,
      as a marker of kidney function, are associated with mortality. To do this, we
      analyzed the available laboratory data of 11,957 adults in the National Health
      and Nutrition Examination Survey 1999-2004 to calculate AG using the traditional
      method, or one that was albumin-adjusted, as well as a full AG reflecting other
      electrolytes. A significant elevation in the traditional AG was seen only with an
      estimated glomerular filtration rate (eGFR) <45 ml/min per 1.73 m(2), whereas
      increases in the albumin-adjusted and full AG were found with eGFRs <60 or 90
      ml/min per 1.73 m(2), respectively. Higher levels of each AG were associated with
      an increased risk of all-cause mortality after adjustment for age, gender,
      race/ethnicity, and eGFR. After adjustment for additional covariates including
      body mass index and comorbidities, higher levels of the albumin-adjusted and full
      AG were associated with mortality (relative hazard for the highest compared with
      the lowest quartile were 1.62 and 1.64, respectively). Thus, higher levels of AG
      are present in individuals with less advanced kidney disease than previously
      recognized, and are associated with increased risk of mortality. Further study is
      needed to identify the unmeasured anions and to determine their physiological
      significance.

PMID- 22622502
TI  - Are calcineurin inhibitors-free regimens ready for prime time?
AB  - The goal of research in transplant therapeutics is to achieve safe and effective
      immunosuppression strategies that allow durable engraftment free of toxicities.
      The calcineurin inhibitors (CNIs) regimens, because of their inherent toxicities
      (including nephrotoxicity), have been unable to meet these promises. Over the
      past decade acute cellular rejection decreased dramatically with a concomitant
      robust increase in 1-year graft survival; however, long-term graft outcome showed
      only modest improvement. This is due in part to the toxicities of the
      immunosuppressive drugs. The quest for a toxicity-free-CNI-free regimen has been
      both intense and frustrating. A turning point in CNIs-free therapy may have
      occurred with the recent approval of belatacept, which represents a new paradigm
      in immunosuppression: biological therapy for chronic immunosuppression devoid of
      the usual toxicities associated with the CNIs. Belatacept, a fusion receptor
      protein, blocks costimulation signals necessary for the activation of T cells.
      Although costimulation blockade has not been shown to induce tolerance, it can
      provide safe and effective immunosuppression without renal or cardiovascular
      toxicities. The approval of belatacept in both the United States and Europe for
      use in renal transplantation will finally push CNI-free regimens into prime time.
      Novel biologics such as ASKP1240 (a human anti-CD40 monoclonal antibody) and one
      small molecule, tofacitinib, may advance further the use of CNI-free regimens in
      organ transplantation.

PMID- 22622503
TI  - Sensing mechanisms involved in Ca2+ and Mg2+ homeostasis.
AB  - Calcium (Ca(2+)) and magnesium (Mg(2+)) ions are involved in many vital
      physiological functions. In the human body, Ca(2+) and Mg(2+) homeostatic systems
      rely on three components: (i) tissues (re)absorbing or storing Ca(2+) and Mg(2+),
      mainly kidney, intestine, and bone; (ii) hormones that modulate the transport and
      mobilization of these minerals; and (iii) sensors controlling the transport of
      Ca(2+) and Mg(2+) in tissues. So far, the Ca(2+)-sensing receptor (CaSR) is the
      only known sensing mechanism involved in the response to systemic and local
      fluctuations in Ca(2+) and Mg(2+) concentrations. The tight coupling of the
      Ca(2+) and Mg(2+) homeostasis is frequently observed in humans and in animal
      models. Moreover, during the past decade, the intense research on mineral
      disorders, seen in the course of chronic kidney disease with secondary
      hyperparathyroidism, has revealed the interplay between Ca(2+) and Mg(2+)
      homeostasis. Altogether this evidence points to the CaSR as an interesting target
      to study mutual disturbances in Ca(2+) and Mg(2+) balance. Although many
      homeostatic processes involving CaSR in the parathyroid glands and kidneys have
      been elucidated, the current knowledge of the inter-regulation of divalent
      handling by the CaSR is still limited. Insight into the systemic and local
      sensing of Ca(2+) and Mg(2+) by the CaSR, as well as the identification of other
      receptors/sensors for these cations, will unravel the mechanism controlling their
      coupled regulation, and will lead to new treatment concepts for mineral
      disorders.

PMID- 22622501
TI  - Tubule-specific ablation of endogenous beta-catenin aggravates acute kidney
      injury in mice.
AB  - beta-Catenin is a unique intracellular protein functioning as an integral
      component of the cell-cell adherens complex and a principal signaling protein
      mediating canonical Wnt signaling. Little is known about its function in adult
      kidneys in the normal physiologic state or after acute kidney injury (AKI). To
      study this, we generated conditional knockout mice in which the beta-catenin gene
      was specifically disrupted in renal tubules (Ksp-beta-cat-/-). These mice were
      phenotypically normal with no appreciable defects in kidney morphology and
      function. In the absence of beta-catenin, gamma-catenin functionally substituted
      for it in E-cadherin binding, thereby sustaining the integrity of epithelial
      adherens junctions in the kidneys. In AKI induced by ischemia reperfusion or
      folic acid, the loss of tubular beta-catenin substantially aggravated renal
      lesions. Compared with controls, Ksp-beta-cat-/- mice displayed higher mortality,
      elevated serum creatinine, and more severe morphologic injury. Consistently,
      apoptosis was more prevalent in kidneys of the knockout mice, which was
      accompanied by increased expression of p53 and Bax, and decreased phosphorylated
      Akt and survivin. In vitro activation of beta-catenin by Wnt1 or stabilization of
      beta-catenin protected tubular epithelial cells from apoptosis, activated Akt,
      induced survivin, and repressed p53 and Bax expression. Hence, endogenous beta
      catenin is pivotal for renal tubular protection after AKI by promoting cell
      survival through multiple mechanisms.

PMID- 22622504
TI  - Donor-specific HLA-DQ antibodies may contribute to poor graft outcome after renal
      transplantation.
AB  - Increasing evidence suggests a detrimental effect of donor-specific antibodies
      directed against the human leukocyte antigen (HLA)-A, -B, and -DR loci on renal
      allograft outcomes. Limited data exist on the impact of de novo HLA-DQ
      antibodies. Over a 3-year period, we prospectively monitored 347 renal transplant
      recipients without pre-transplant donor-specific antibodies for their development
      de novo. After 26 months of follow-up, 62 patients developed donor-specific
      antibodies, of which 48 had a HLA-DQ antibody either alone (33 patients) or in
      combination with an HLA-A, -B, or -DR antibody (15 patients). Only 14 patients
      developed a donor-specific HLA-A, -B, or -DR antibody without a HLA-DQ antibody
      present. Acute rejection occurred in 21% of the HLA-DQ-only patients,
      insignificant when compared with 11% of patients without donor-specific
      antibodies. At the last follow-up, the mean serum creatinine and the fraction of
      patients with proteinuria were significantly higher in those that developed only
      HLA-DQ than those without antibodies. The 3-year graft survival was significantly
      worse when HLA-DQ antibodies were combined with non-DQ antibodies (52%) compared
      with HLA-DQ alone, non-DQ antibodies alone, or no antibodies (92-94%). Thus, our
      prospective monitoring study found that donor-specific HLA-DQ antibodies were the
      most common type detected and these antibodies may contribute to inferior graft
      outcomes. Ongoing surveillance is necessary to determine the long-term outcome of
      patients developing HLA-DQ donor-specific antibodies.

PMID- 22622505
TI  - Three novel organic-inorganic complexes based on decavanadate [V10O28]6- units:
      special water layers, open 3D frameworks and yellow/blue luminescences.
AB  - Three unusual polyoxovanadate-based inorganic-organic hybrid complexes,
      [Zn(Im)(2)(DMF)(2)](2)[H(2)V(10)O(28)].Im.DMF (1),
      [Zn(3)(Htrz)(6)(H(2)O)(6)][V(10)O(28)].10H(2)O.Htrz (2) and
      {[Zn(3)(trz)(3)(H(2)O)(4)(DMF)](2)[V(10)O(28)].4H(2)O}(n) (3) (Im = imidazole,
      Htrz = 1,2,4-triazole, DMF = N,N'-dimethylammonium) have been synthesized at room
      temperature via evaporative crystallization, and characterized by single-crystal
      X-ray diffraction. Complex 1 shows the structure of a discrete [V(10)O(28)](6-)
      cluster grafted by two [Zn(Im)(2)(DMF)(2)](2+) fragments through two bridged
      oxygen atoms, representing a rarely observed coordination mode. Complex 2
      consists of a linear trinuclear Zn(II) unit bridging six Htrz ligands and a
      [V(10)O(28)](6-) cluster as the counter anion, where the extensive hydrogen
      bonding interactions lead to {Zn(3)-V(10)}(SMF) and a special water layer
      involving (H(2)O)(36) rings, and consequently forms a unique 3D metal-organic
      water supramolecular network. Complex 3 can be described as a 3,4-connected fsc
      type network, and is the first example of open coordination 3D framework based on
      [V(10)O(28)](6-) and the other two different secondary building units, involving
      mononuclear and binuclear Zn(II)-Htrz motifs. The optical properties of complexes
      1-3 in the solid state are investigated at room temperature. The results show
      that complexes 1 and 3 emit intense blue luminescences attributed to the ligands,
      while complex 2 exhibits an infrequent fluorescent property, emitting both blue
      and yellow luminescences at 472 and 603 nm simultaneously. Furthermore, powder X
      ray diffraction and thermogravimetric analyses of 1-3 are also investigated,
      which demonstrate their high purities and thermal stabilities.

PMID- 22622506
TI  - [New methods of drug delivery through the blood brain barrier].

PMID- 22622507
TI  - Chest wall reconstruction with a lateral thoracic artery perforator propeller
      flap for a radiation ulcer on the anterior chest.
AB  - A lateral thoracic artery perforator propeller flap is advantageous because it
      does not require microvascular anastomosis, only rarely involves donor-site
      morbidity and provides sufficient blood flow. Moreover, by rotating the flap,
      remote tissues with less radiation-induced damage can be used at the site of the
      defect. In this article, we report the use of a lateral thoracic artery
      perforator propeller flap to treat a radiation ulcer.

PMID- 22622508
TI  - Perforator-bridged lymphaticovenular anastomosis.

PMID- 22622509
TI  - Effect of direction (epidermis-to-dermis and dermis-to-epidermis) on the
      permeation of several chemical compounds through full-thickness skin and stripped
      skin.
AB  - PURPOSE: Compound permeation through stratum corneum-stripped skin is generally
      greater than that through full-thickness skin. In addition, epidermis-to-dermis
      permeation profile should be the same as dermis-to-epidermis permeation profile.
      However, stripped skin permeability of some compounds was lower than full
      thickness skin permeability and different permeabilities were found for some
      compounds between the two directions of skin permeation. The reasons for these
      findings were investigated in this study. METHODS: Full-thickness or stripped
      hairless rat skin was set in a Franz-type diffusion cell, and a solution of
      compound was applied on the epidermis or dermis side to determine the in vitro
      skin permeability. RESULTS: Although the stripped skin permeability of pentyl
      paraben (PeP) with extremely high logK(o/w) was lower than full-thickness skin
      permeabilities, the addition of 3% ethanol resulted in the expected permeation
      order. Epidermis-to-dermis permeation of PeP through full-thickness skin was
      higher than dermis-to-epidermis permeation. Epidermis-to-dermis permeations of
      fluorescein isothiocyanate dextran (FD-4) and isosorbide 5-mononitrate with
      negative logK(o/w) were also higher than those in the opposite direction.
      CONCLUSIONS: Morphological observation of skin after FD-4 permeation suggested
      that a conically shaped trans-follicular permeation pathway model could be
      advocated to explain the difference between the epidermis-to-dermis permeation
      and that in the opposite direction.

PMID- 22622510
TI  - Dextran-catechin conjugate: a potential treatment against the pancreatic ductal
      adenocarcinoma.
AB  - PURPOSE: A polysaccharide-flavonoid conjugate was developend and proposed for the
      treatment of pancreatic ductal adenocarcinoma (PDAC). METHODS: The conjugate was
      synthesized by free radical grafting reaction between catechin and dextran. The
      chemical characterization of the conjugate was obtained by UV-Vis, 1H-NMR, FT-IR
      and GPC analyses, while the functionalization degree was determined by the Folin
      Ciocalteu assay. The biological activity of the catechin-dextran conjugate was
      tested on two different cell lines derived from human pancreatic cancer (MIA PaCa
      2 and PL45 cells), and the toxicity towards human pancreatic nestin-expressing
      cells evaluated. RESULTS: Both the cancer cell lines are killed when exposed to
      the conjugate, and undergo apoptosis after the incubation with catechin-dextran
      which resulted more effective in killing pancreatic tumor cells compared to the
      catechin alone. Moreover, our experimental data indicate that the conjugate was
      less cytotoxic to human pancreatic nestin-expressing cells which are considered a
      good model of non-neoplastic pancreatic cells. CONCLUSION: The suitability of
      newly synthesized Dextran-Catechin conjugate in the treatment of PDAC was proved
      confirming the high potential application of the proposed macromolecula system in
      the cancer therapy.

PMID- 22622511
TI  - Evaluation of 2009 pandemic influenza A (H1N1) exposures and illness among
      physicians in training.
AB  - BACKGROUND: A cluster of influenza-like illness (ILI) among physicians in
      training during the 2009 influenza A (H1N1) pandemic (pH1N1) led to a health
      hazard evaluation. METHODS: We conducted a cross-sectional study to examine
      exposures, infection control practices, ILI prevalence, and transmission among
      physicians in training at 4 affiliated hospitals during the pandemic. We
      administered an electronic survey and met with physicians in training and
      hospital personnel. RESULTS: Of the 88 responding physicians, 85% reported
      exposure to pH1N1. Exposures occurred at work from patients or coworkers and
      outside of work from coworkers, household members, or the community. Thirteen
      cases of ILI were reported in May-June 2009; 10 respondents reported working
      while ill (duration, 1-4 days). Between 13% and 88% of respondents knew which
      personal protective equipment (PPE) was recommended when caring for influenza
      patients at the 4 hospitals. The most common reasons for not using PPE were not
      knowing that a patient had pH1N1 or ILI and not having PPE readily available.
      CONCLUSIONS: Physicians in training have gaps in their knowledge of and adherence
      to recommended PPE and compliance with work restrictions. Our findings underscore
      the importance of installing isolation precaution signage, making PPE readily
      available near patients with influenza, and facilitating work restrictions for
      ill health care personnel.

PMID- 22622512
TI  - Applying validated quality indicators to surgical antibiotic prophylaxis in a
      Brazilian hospital: learning what should be learned.
AB  - BACKGROUND: Compliance with the best surgical antibiotic prophylaxis practice is
      usually low despite many published guidelines. OBJECTIVE: This study investigated
      compliance with the Hospital Infection Control Committee guideline for antibiotic
      prophylaxis in a Brazilian hospital using quality indicators. METHODS: A
      retrospective study was carried out from November 2009 to March 2010. Medical
      records from adult inpatients undergoing cardiac, neurologic, and orthopedic
      clean surgeries were included. The full compliance index was considered 100% when
      the antibiotic prophylaxis showed adequacy in all evaluated attributes. Analyses
      were conducted with 5% significance. RESULTS: Medical records from 101 cardiac,
      128 neurologic, and 519 orthopedic surgical patients were evaluated. The
      compliance index was 4.9%, and the compliance index according to specialty was
      5.8%, 3.1%, and 3.0%, respectively, for orthopedic, neurologic, and cardiac
      surgeries. The attribute route of administration produced the best outcomes,
      whereas the attribute duration of antibiotic prophylaxis produced the worst. No
      association was identified between compliance to the attributes and patient
      characteristics. CONCLUSION: This study showed a low level of adherence to
      Hospital Infection Control Committee guidelines for antibiotic prophylaxis. This
      suggests that different strategies should be implemented to promote the best
      possible practice in the field of antibiotic prophylaxis with greater surgeon
      engagement.

PMID- 22622513
TI  - Are gym surfaces reservoirs for Staphylococcus aureus? A point prevalence survey.
AB  - We sought to identify staphylococcal contamination of gymnasium surfaces. Various
      environmental surfaces were cultured at a university fitness center. Ten out of
      99 samples yielded Staphylococcus aureus, all of which were methicillin
      susceptible. Gym surfaces may be colonized with staphylococci and could play a
      role in community transmission of staphylococcal species.

PMID- 22622514
TI  - Emergency management of severe sepsis and septic shock.
AB  - PURPOSE OF REVIEW: Numerous implementation studies have demonstrated the benefit
      of bundled care in the initial treatment of patients with severe sepsis and
      septic shock, but the relative value of each component of these bundles remains
      uncertain. Recent studies have attempted to further define the optimal supportive
      and adjunctive treatments for these patients. RECENT FINDINGS: The choice of
      optimal intravenous resuscitation fluid for the emergency treatment of severe
      sepsis remains uncertain. Albumin appears safe, although safety concerns have
      arisen regarding the use of hydroxyethyl starch. Norepinephrine and vasopressin
      appear superior to dopamine as vasopressors of choice. Several studies have
      successfully incorporated lactate clearance into resuscitation strategies, albeit
      with differing protocols. Although corticosteroids may hasten improvement, there
      does not appear to be a mortality benefit in heterogeneous patients with sepsis,
      leaving their role uncertain. SUMMARY: Recent negative studies have questioned
      the role of previously promising adjunctive treatments. However, recent clinical
      trials and meta-analytic data continue to refine the relative importance of
      various components of sepsis bundles.

PMID- 22622515
TI  - Management of atrial fibrillation in the acute setting.
AB  - PURPOSE OF REVIEW: The review aims to describe the scope of the problem and
      potential therapeutic intervention for the management and risk stratification of
      patients with atrial fibrillation in the emergency department and acute care
      setting. RECENT FINDINGS: Atrial fibrillation is the most common arrhythmia
      prompting admission to the hospital. Management strategies include determining
      the trigger of the arrhythmia, rate control, and potential cardioversion. In the
      acute care setting the treatment is often dependent on the timing of the onset of
      arrhythmia. In those patients presenting with symptoms of less than 48 h of
      duration management may consist of rate control, pharmacologic, or electrical
      cardioversion. Recent studies suggest no difference in long-term outcomes with
      rate and rhythm control. In patients with symptoms greater that 48 h rate control
      is the initial option with potential for cardioversion as an outpatient. There
      are recent advances in ablation that provide additional options to patients with
      paroxysmal atrial fibrillation. An essential component of the treatment strategy
      for these patients is risk stratification for stroke and the initiation of long
      term anticoagulation in appropriate patients. SUMMARY: Management of atrial
      fibrillation is guided by underlying causes of the atrial fibrillation and
      duration of symptoms.

PMID- 22622517
TI  - Traumatic diaphragmatic hernia in children.
AB  - BACKGROUND: Traumatic diaphragmatic hernia (TDH) is very rare in the pediatric
      age group. Because of its rarity and its coexistence with more serious injuries,
      the diagnosis is often missed or delayed. PATIENTS AND METHODS: All children with
      the diagnosis of TDH were retrospectively reviewed for age at diagnosis, sex,
      mechanism of injury, site of diaphragmatic rupture, associated injuries, injury
      severity score, investigations, treatment and outcome. RESULTS: Over a period of
      15 years (1992-2007), we treated seven children with TDH. All were males except
      one. Their mean age was 7.4 years (3.75-14 years). The site of TDH was on the
      left in three, on the right in three and one had bilateral TDH. The mechanism of
      injury was blunt trauma in six and penetrating injury from a stab in one. Three
      had right TDH and in all three, the diagnosis of TDH was delayed. All sustained
      severe injuries as reflected by the ISS score (mean 38.6). The time from
      presentation to diagnosis was variable ranging from 3 to 240 h (mean 65.7 h). The
      three patients with left TDH were repaired trans-abdominally while the three with
      right TDH were repaired via a right thoracotomy. The patient with bilateral TDH
      required laparotomy and thoracotomy. All our patients survived and the hospital
      stay was variable ranging from 7 to 24 days (mean 17 days). CONCLUSIONS: TDH is
      very rare in children and often associated with severe more serious injuries.
      These two factors contribute to the delay in diagnosis. This is specially so for
      right TDH. To obviate delay in diagnosis, it is important to have a high index of
      suspicion as well as careful interpretation of the initial and follow-up
      radiological investigations including CT-scan of the chest and abdomen. This is
      important to detect a slowly increasing TDH that may not be apparent initially.

PMID- 22622518
TI  - Missed opportunities in the treatment of pediatric appendicitis.
AB  - INTRODUCTION: This study sought to evaluate the outcomes of in-hospital delay and
      determine associated co-morbidities in the treatment of pediatric acute
      appendicitis. METHODS: This was a retrospective analysis of the national
      inpatient sample from 2000 to 2008. Immediate treatment was defined as treatment
      in hospital day 0 or 1. Delay in treatment was defined as treatment in hospital
      day 2 and beyond. RESULTS: During the study period, 683,016 pediatric
      appendicitis were identified. 17,737 (2.6%) experienced a delay in treatment.
      Multivariate analysis identified associated co-morbidities for delay in
      treatment: ALL (OR 12.84, CI 11.04-14.94), AML (OR 9.41, CI 7.58-11.68),
      neutropenia (OR 5.53, CI 4.60-6.65), and ovarian cyst without torsion (OR 3.17,
      CI 2.94-3.42). Surgical management included more than 13-fold increase in
      drainage procedures (5.5 vs. 0.4%), sixfold increase in cecectomy (1.2 vs. 0.2%),
      14-fold increase in hemicolectomy (1.4 vs. 0.1%), 11-fold increase in small bowel
      laceration suture repair (1.1 vs. 0.1%), and 15-fold increase in small bowel
      resection (1.5 vs. 0.1%). CONCLUSIONS: In-hospital delay beyond 2 days is
      associated with significant negative outcomes with regard to complications,
      economic burden, and subsequent surgical management. Using the co-morbidity
      index, high-risk co-morbidities with associated delay in treatment were
      identified.

PMID- 22622516
TI  - BMP9 induces EphrinB2 expression in endothelial cells through an Alk1
      BMPRII/ActRII-ID1/ID3-dependent pathway: implications for hereditary hemorrhagic
      telangiectasia type II.
AB  - ALK1 (ACVRL1) is a member of the TGFbeta receptor family and is expressed
      predominantly by arterial endothelial cells (EC). Mutations in ACVRL1 are
      responsible for hereditary hemorrhagic telangiectasia type 2 (HHT2), a disease
      manifesting as fragile vessels, capillary overgrowth, and numerous arterio-venous
      malformations. Arterial EC also express EphrinB2, which has multiple roles in
      vascular development and angiogenesis and is known to be reduced in ACVRL1
      knockout mice. Using an in vitro angiogenesis model we find that the Alk1 ligand
      BMP9 induces EphrinB2 in EC, and this is entirely dependent on expression of Alk1
      and at least one of the co-receptors BMPRII or ActRII. BMP9 induces both ID1 and
      ID3, and both are necessary for full induction of EphrinB2. Loss of Alk1 or
      EphrinB2 results in increased arterial-venous anastomosis, while loss of Alk1 but
      not EphrinB2 results in increased VEGFR2 expression and enhanced capillary
      sprouting. Conversely, BMP9 blocks EC sprouting and this is dependent on Alk1,
      BMPRII/ActRII and ID1/ID3. Finally, notch signaling overcomes the loss of Alk1
      restoring EphrinB2 expression in EC, and curbing excess sprouting. Thus, in an in
      vitro model of HHT2, loss of Alk1 blocks BMP9 signaling, resulting in reduced
      EphrinB2 expression, enhanced VEGFR2 expression, and misregulated EC sprouting
      and anastomosis.

PMID- 22622519
TI  - Teratoma with somatic-type malignant components of the testis. A review and an
      update.
AB  - Malignant transformation of germ cell tumors into somatic malignancy is uncommon.
      Its presentation differs from series to series, with 43 % of adult cases
      identified within the primary tumors and the remainder at the time of relapse or
      in the metastasis. Patients with stage I disease enjoy an excellent prognosis;
      whereas in metastatic sites when not completely resectable, the somatic type
      malignancies suffer a dismal prognosis. Radical surgery is significant for the
      prospects of cure and is standard chemotherapy for germ cell tumors; a
      transformation-oriented treatment can be effective for these patients. A deeper
      understanding of the biology of this phenomenon is essential for clinicians
      involved in such malignancies in order to permit a better control of the disease.

PMID- 22622520
TI  - Diversity and linkage disequilibrium features in a composite public/private dent
      maize panel: consequences for association genetics as evaluated from a case study
      using flowering time.
AB  - Recent progress in genotyping and resequencing techniques have opened new
      opportunities for deciphering quantitative trait variation by looking for
      associations between traits of interest and polymorphisms in panels of diverse
      inbred lines. Association mapping raises specific issues related to the choice of
      appropriate (i) panels and marker-densities and (ii) statistical methods to
      capture associations. In this study, we used a panel of 314 maize inbred lines
      from the dent pool, composed of inbred material from public institutes (113
      inbred lines) and a private company (201 inbred lines). We showed that local LD
      was higher and genetic diversity lower in the material of private origin than in
      the public material. We compared the results obtained by different software for
      identifying population structure and computing relatedness among lines, and ran
      association tests for earliness related traits. Our results confirmed the
      importance of the mite polymorphism of Vgt1 on flowering time, but also showed
      that its effect can be captured by zmRap2.7 polymorphisms located 70 kb apart. We
      also highlighted associations with polymorphisms within genes putatively involved
      in lignin biosynthesis pathway, which deserve further investigations.

PMID- 22622523
TI  - Microsurgical treatment of an ethmoidal dural fistula:  3-dimensional
      illustration.

PMID- 22622521
TI  - Overview of LASSO-related penalized regression methods for quantitative trait
      mapping and genomic selection.
AB  - Quantitative trait loci (QTL)/association mapping aims at finding genomic loci
      associated with the phenotypes, whereas genomic selection focuses on breeding
      value prediction based on genomic data. Variable selection is a key to both of
      these tasks as it allows to (1) detect clear mapping signals of QTL activity, and
      (2) predict the genome-enhanced breeding values accurately. In this paper, we
      provide an overview of a statistical method called least absolute shrinkage and
      selection operator (LASSO) and two of its generalizations named elastic net and
      adaptive LASSO in the contexts of QTL mapping and genomic breeding value
      prediction in plants (or animals). We also briefly summarize the Bayesian
      interpretation of LASSO, and the inspired hierarchical Bayesian models. We
      illustrate the implementation and examine the performance of methods using three
      public data sets: (1) North American barley data with 127 individuals and 145
      markers, (2) a simulated QTLMAS XII data with 5,865 individuals and 6,000 markers
      for both QTL mapping and genomic selection, and (3) a wheat data with 599
      individuals and 1,279 markers only for genomic selection.

PMID- 22622522
TI  - Indocyanine green angiography findings in patients with nonfamilial amyloidosis.
AB  - PURPOSE: The purpose of this study is to assess indocyanine green angiographic
      findings in patients with nonfamilial amyloidosis. METHODS: The method used was a
      prospective study including seven patients (14 eyes) with nonfamilial
      amyloidosis. All patients underwent detailed ophthalmic clinical examination,
      fundus photography, and indocyanine green angiography (ICGA). Fluorescein
      angiography (FA) was performed in four patients. RESULTS: Of the seven patients,
      four (57.1 %) were male. Mean age was 49.5 years. Six patients had renal
      amyloidosis and one patient had systemic amyloidosis. Mean best-corrected visual
      acuity was 20/25. Fundus and FA findings included cotton-wool spots (28.5 %),
      retinal hemorrhages (14.3 %), retinal pigment epithelial changes (21.4 %), serous
      retinal detachment (7.1 %), optic disk edema or staining (7.1 %), area of
      peripheral retinal capillary non-perfusion (7.1 %), disseminated peripheral
      punctiform hyperfluorescence (21.4 %), and subretinal pooling (7.1 %). Fundus
      examination results were unremarkable in eight eyes (57.1 %). ICGA showed
      abnormal findings in all eyes. These included diffuse or focal/multifocal
      choroidal vascular staining appearing at the late phase and prevailing in
      peripheral fundus (100 %), hyperfluorescent fleecy lesions appearing at the late
      phase and also prevailing in peripheral fundus (28.5 %), hypofluoresent areas of
      variable sizes (85.7 %), and pinpoints (71.4 %). CONCLUSIONS: Our results show
      that a subclinical, fairly typical choroidal involvement, detectable only by
      ICGA, is common in patients with nonfamilial amyloidosis. ICGA may be useful in
      better understanding the pathogenesis of amyloidosis choroidopathy and in
      establishing a diagnosis of amyloidosis in atypical or incomplete clinical
      presentations.

PMID- 22622524
TI  - Electroactive subwavelength gratings (ESWGs) from conjugated polymers for color
      and intensity modulation.
AB  - Subwavelength gratings with electroactive polymers such as poly(3-hexylthiophene)
      (P3HT) and poly(3,4-propylenedioxythiophene-phenylene) (P(ProDOT-Ph)) controlled
      the color intensity for various visible colors of diffracted light in a single
      device. Under the illumination of a white light, at a fixed angle of incidence,
      the color intensity of the diffracted light was reversibly switched from the
      maximum value down to 15% (85% decrease) by applying -2 to 2 V due to
      electrochemical (EC) reaction. All spectral colors including red, green, and blue
      were generated by changing the angle of incidence, and the intensity of each
      color was modulated electrochemically at a single EC device. With electroactive
      subwavelength gratings (ESWGs) of P3HT, the maximum modulation of the color
      intensity was observed in the red-yellow quadrant in the CIE color plot, whereas
      for the ESWGs of P(ProDOT-Ph), the maximum modulation of the color intensity was
      observed in the yellow-green and green-blue quadrants. Both ESWGs showed a memory
      effect, keeping their color and intensity even after power was turned off for
      longer than 40 hours.

PMID- 22622526
TI  - A rare chromosomal abnormality inherited from the mother in a boy conceived after
      intracytoplasmic sperm injection: a case report.

PMID- 22622527
TI  - Enantioselective metallo-organocatalyzed preparation of cyclopentanes bearing an
      all-carbon quaternary stereocenter.
AB  - Enantioselective metallo-organocatalyzed carbocyclizations of formyl-alkynes have
      been developed. The cooperation between aminocatalysis and a chiral copper(I)
      complex granted access to enantio-enriched cyclopentanes through the challenging
      formation of all-carbon quaternary stereocenters.

PMID- 22622525
TI  - GSTM1 null genotype contributes to increased risk of male infertility: a meta
      analysis.
AB  - BACKGROUND: Many studies have investigated the association between Glutathione S
      Transferase M 1 (GSTM1) null genotype and risk of male infertility, but the
      impact of GSTM1 null genotype on infertility risk is unclear owing to the obvious
      inconsistency among those studies. This study aimed to quantify the strength of
      association between GSTM1 null genotype and risk of male infertility. METHODS: We
      searched the PubMed, Embase and Wangfang databases for studies investigating the
      association between GSTM1 null genotype and risk of male infertility. We
      estimated pooled odds ratio (OR) with its 95 % confidence interval (95 % CI) to
      assess this possible association. RESULTS: Twelve case-control studies with 1,
      589 infertility cases and 1, 537 controls were included. Meta-analysis of total
      12 studies showed that GSTM1 null genotype was associated with increased risk of
      male infertility (OR = 1.34, 95%CI 1.02-1.77, P = 0.036). In subgroup analysis of
      Caucasians, there was also an obvious association between GSTM1 null genotype and
      increased risk of male infertility (OR = 1.51, 95%CI 1.11-2.05, P = 0.006).
      Sensitivity analyses by sequential omission of individual studies or omitting
      studies without high quality did not significantly alter the overall pooled OR.
      Cumulative meta-analysis further showed a trend of more obvious association as
      information accumulated. No evidence of publication bias was observed.
      CONCLUSION: Meta-analyses of available data suggest that GSTM1 null genotype
      contributes to increased risk of male infertility.

PMID- 22622528
TI  - A charter for geoengineering.

PMID- 22622529
TI  - In from the cold.

PMID- 22622530
TI  - A whale of a story.

PMID- 22622531
TI  - We must set planetary boundaries wisely.

PMID- 22622542
TI  - Fukushima's doses tallied.

PMID- 22622543
TI  - Biosafety concerns for labs in the developing world.

PMID- 22622544
TI  - US government sets out Alzheimer's plan.

PMID- 22622545
TI  - Global council aims to coordinate science.

PMID- 22622546
TI  - Hubble to revisit exoplanet puzzle.

PMID- 22622547
TI  - Cancelled project spurs debate over geoengineering patents.

PMID- 22622548
TI  - War on weeds loses ground.

PMID- 22622550
TI  - Bird-flu research: The biosecurity oversight.

PMID- 22622551
TI  - Gran Sasso: Chamber of physics.

PMID- 22622552
TI  - Antibiotics: Recover the lost art of drug discovery.

PMID- 22622553
TI  - Environmental science: The hidden costs of flexible fertility.

PMID- 22622558
TI  - Publishing: Careless linking of Wallace and Darwin.

PMID- 22622559
TI  - Microbiology: Categorize probiotics to speed research.

PMID- 22622560
TI  - Pathogens: Monitoring fungal infections in fish.

PMID- 22622561
TI  - Botany: Support home-grown plant collectors.

PMID- 22622562
TI  - Climate change: Flowering in the greenhouse.

PMID- 22622563
TI  - Applied chemistry: Molecules meet materials.

PMID- 22622564
TI  - Alzheimer's disease: A breach in the blood-brain barrier.

PMID- 22622565
TI  - Geochemistry: Portrait of Earth's coming of age.

PMID- 22622566
TI  - Neuroscience: Crystal-clear brains.

PMID- 22622567
TI  - Particle physics: A reminder of the beauty we know.

PMID- 22622568
TI  - Astrophysics: Startling superflares.

PMID- 22622569
TI  - Peroxiredoxins are conserved markers of circadian rhythms.
AB  - Cellular life emerged ~3.7 billion years ago. With scant exception, terrestrial
      organisms have evolved under predictable daily cycles owing to the Earth's
      rotation. The advantage conferred on organisms that anticipate such environmental
      cycles has driven the evolution of endogenous circadian rhythms that tune
      internal physiology to external conditions. The molecular phylogeny of mechanisms
      driving these rhythms has been difficult to dissect because identified clock
      genes and proteins are not conserved across the domains of life: Bacteria,
      Archaea and Eukaryota. Here we show that oxidation-reduction cycles of
      peroxiredoxin proteins constitute a universal marker for circadian rhythms in all
      domains of life, by characterizing their oscillations in a variety of model
      organisms. Furthermore, we explore the interconnectivity between these metabolic
      cycles and transcription-translation feedback loops of the clockwork in each
      system. Our results suggest an intimate co-evolution of cellular timekeeping with
      redox homeostatic mechanisms after the Great Oxidation Event ~2.5 billion years
      ago.

PMID- 22622570
TI  - Rab5 is necessary for the biogenesis of the endolysosomal system in vivo.
AB  - An outstanding question is how cells control the number and size of membrane
      organelles. The small GTPase Rab5 has been proposed to be a master regulator of
      endosome biogenesis. Here, to test this hypothesis, we developed a mathematical
      model of endosome dependency on Rab5 and validated it by titrating down all three
      Rab5 isoforms in adult mouse liver using state-of-the-art RNA interference
      technology. Unexpectedly, the endocytic system was resilient to depletion of Rab5
      and collapsed only when Rab5 decreased to a critical level. Loss of Rab5 below
      this threshold caused a marked reduction in the number of early endosomes, late
      endosomes and lysosomes, associated with a block of low-density lipoprotein
      endocytosis. Loss of endosomes caused failure to deliver apical proteins to the
      bile canaliculi, suggesting a requirement for polarized cargo sorting. Our
      results demonstrate for the first time, to our knowledge, the role of Rab5 as an
      endosome organizer in vivo and reveal the resilience mechanisms of the endocytic
      system.

PMID- 22622572
TI  - Superflares on solar-type stars.
AB  - Solar flares are caused by the sudden release of magnetic energy stored near
      sunspots. They release 10(29) to 10(32) ergs of energy on a timescale of hours.
      Similar flares have been observed on many stars, with larger 'superflares' seen
      on a variety of stars, some of which are rapidly rotating and some of which are
      of ordinary solar type. The small number of superflares observed on solar-type
      stars has hitherto precluded a detailed study of them. Here we report
      observations of 365 superflares, including some from slowly rotating solar-type
      stars, from about 83,000 stars observed over 120 days. Quasi-periodic brightness
      modulations observed in the solar-type stars suggest that they have much larger
      starspots than does the Sun. The maximum energy of the flare is not correlated
      with the stellar rotation period, but the data suggest that superflares occur
      more frequently on rapidly rotating stars. It has been proposed that hot Jupiters
      may be important in the generation of superflares on solar-type stars, but none
      have been discovered around the stars that we have studied, indicating that hot
      Jupiters associated with superflares are rare.

PMID- 22622571
TI  - Brain-wide neuronal dynamics during motor adaptation in zebrafish.
AB  - A fundamental question in neuroscience is how entire neural circuits generate
      behaviour and adapt it to changes in sensory feedback. Here we use two-photon
      calcium imaging to record the activity of large populations of neurons at the
      cellular level, throughout the brain of larval zebrafish expressing a genetically
      encoded calcium sensor, while the paralysed animals interact fictively with a
      virtual environment and rapidly adapt their motor output to changes in visual
      feedback. We decompose the network dynamics involved in adaptive locomotion into
      four types of neuronal response properties, and provide anatomical maps of the
      corresponding sites. A subset of these signals occurred during behavioural
      adjustments and are candidates for the functional elements that drive motor
      learning. Lesions to the inferior olive indicate a specific functional role for
      olivocerebellar circuitry in adaptive locomotion. This study enables the analysis
      of brain-wide dynamics at single-cell resolution during behaviour.

PMID- 22622573
TI  - Tunable ion-photon entanglement in an optical cavity.
AB  - Proposed quantum networks require both a quantum interface between light and
      matter and the coherent control of quantum states. A quantum interface can be
      realized by entangling the state of a single photon with the state of an atomic
      or solid-state quantum memory, as demonstrated in recent experiments with trapped
      ions, neutral atoms, atomic ensembles and nitrogen-vacancy spins. The entangling
      interaction couples an initial quantum memory state to two possible light-matter
      states, and the atomic level structure of the memory determines the available
      coupling paths. In previous work, the transition parameters of these paths
      determined the phase and amplitude of the final entangled state, unless the
      memory was initially prepared in a superposition state (a step that requires
      coherent control). Here we report fully tunable entanglement between a single
      (40)Ca(+) ion and the polarization state of a single photon within an optical
      resonator. Our method, based on a bichromatic, cavity-mediated Raman transition,
      allows us to select two coupling paths and adjust their relative phase and
      amplitude. The cavity setting enables intrinsically deterministic, high-fidelity
      generation of any two-qubit entangled state. This approach is applicable to a
      broad range of candidate systems and thus is a promising method for distributing
      information within quantum networks.

PMID- 22622574
TI  - All-solid-state dye-sensitized solar cells with high efficiency.
AB  - Dye-sensitized solar cells based on titanium dioxide (TiO(2)) are promising low
      cost alternatives to conventional solid-state photovoltaic devices based on
      materials such as Si, CdTe and CuIn(1-x)Ga(x)Se(2) (refs 1, 2). Despite offering
      relatively high conversion efficiencies for solar energy, typical dye-sensitized
      solar cells suffer from durability problems that result from their use of organic
      liquid electrolytes containing the iodide/tri-iodide redox couple, which causes
      serious problems such as electrode corrosion and electrolyte leakage.
      Replacements for iodine-based liquid electrolytes have been extensively studied,
      but the efficiencies of the resulting devices remain low. Here we show that the
      solution-processable p-type direct bandgap semiconductor CsSnI(3) can be used for
      hole conduction in lieu of a liquid electrolyte. The resulting solid-state dye
      sensitized solar cells consist of CsSnI(2.95)F(0.05) doped with SnF(2),
      nanoporous TiO(2) and the dye N719, and show conversion efficiencies of up to
      10.2 per cent (8.51 per cent with a mask). With a bandgap of 1.3 electronvolts,
      CsSnI(3) enhances visible light absorption on the red side of the spectrum to
      outperform the typical dye-sensitized solar cells in this spectral region.

PMID- 22622575
TI  - Statistical geochemistry reveals disruption in secular lithospheric evolution
      about 2.5 Gyr ago.
AB  - The Earth has cooled over the past 4.5 billion years (Gyr) as a result of surface
      heat loss and declining radiogenic heat production. Igneous geochemistry has been
      used to understand how changing heat flux influenced Archaean geodynamics, but
      records of systematic geochemical evolution are complicated by heterogeneity of
      the rock record and uncertainties regarding selection and preservation bias. Here
      we apply statistical sampling techniques to a geochemical database of about
      70,000 samples from the continental igneous rock record to produce a
      comprehensive record of secular geochemical evolution throughout Earth history.
      Consistent with secular mantle cooling, compatible and incompatible elements in
      basalts record gradually decreasing mantle melt fraction through time.
      Superimposed on this gradual evolution is a pervasive geochemical discontinuity
      occurring about 2.5 Gyr ago, involving substantial decreases in mantle melt
      fraction in basalts, and in indicators of deep crustal melting and fractionation,
      such as Na/K, Eu/Eu* (europium anomaly) and La/Yb ratios in felsic rocks. Along
      with an increase in preserved crustal thickness across the Archaean/Proterozoic
      boundary, these data are consistent with a model in which high-degree Archaean
      mantle melting produced a thick, mafic lower crust and consequent deep crustal
      delamination and melting--leading to abundant tonalite-trondhjemite-granodiorite
      magmatism and a thin preserved Archaean crust. The coincidence of the observed
      changes in geochemistry and crustal thickness with stepwise atmospheric oxidation
      at the end of the Archaean eon provides a significant temporal link between deep
      Earth geochemical processes and the rise of atmospheric oxygen on the Earth.

PMID- 22622576
TI  - Warming experiments underpredict plant phenological responses to climate change.
AB  - Warming experiments are increasingly relied on to estimate plant responses to
      global climate change. For experiments to provide meaningful predictions of
      future responses, they should reflect the empirical record of responses to
      temperature variability and recent warming, including advances in the timing of
      flowering and leafing. We compared phenology (the timing of recurring life
      history events) in observational studies and warming experiments spanning four
      continents and 1,634 plant species using a common measure of temperature
      sensitivity (change in days per degree Celsius). We show that warming experiments
      underpredict advances in the timing of flowering and leafing by 8.5-fold and 4.0
      fold, respectively, compared with long-term observations. For species that were
      common to both study types, the experimental results did not match the
      observational data in sign or magnitude. The observational data also showed that
      species that flower earliest in the spring have the highest temperature
      sensitivities, but this trend was not reflected in the experimental data. These
      significant mismatches seem to be unrelated to the study length or to the degree
      of manipulated warming in experiments. The discrepancy between experiments and
      observations, however, could arise from complex interactions among multiple
      drivers in the observational data, or it could arise from remediable artefacts in
      the experiments that result in lower irradiance and drier soils, thus dampening
      the phenological responses to manipulated warming. Our results introduce
      uncertainty into ecosystem models that are informed solely by experiments and
      suggest that responses to climate change that are predicted using such models
      should be re-evaluated.

PMID- 22622577
TI  - Discovery of a sensory organ that coordinates lunge feeding in rorqual whales.
AB  - Top ocean predators have evolved multiple solutions to the challenges of feeding
      in the water. At the largest scale, rorqual whales (Balaenopteridae) engulf and
      filter prey-laden water by lunge feeding, a strategy that is unique among
      vertebrates. Lunge feeding is facilitated by several morphological
      specializations, including bilaterally separate jaws that loosely articulate with
      the skull, hyper-expandable throat pleats, or ventral groove blubber, and a rigid
      y-shaped fibrocartilage structure branching from the chin into the ventral groove
      blubber. The linkages and functional coordination among these features, however,
      remain poorly understood. Here we report the discovery of a sensory organ
      embedded within the fibrous symphysis between the unfused jaws that is present in
      several rorqual species, at both fetal and adult stages. Vascular and nervous
      tissue derived from the ancestral, anterior-most tooth socket insert into this
      organ, which contains connective tissue and papillae suspended in a gel-like
      matrix. These papillae show the hallmarks of a mechanoreceptor, containing nerves
      and encapsulated nerve termini. Histological, anatomical and kinematic evidence
      indicate that this sensory organ responds to both the dynamic rotation of the
      jaws during mouth opening and closure, and ventral groove blubber expansion
      through direct mechanical linkage with the y-shaped fibrocartilage structure.
      Along with vibrissae on the chin, providing tactile prey sensation, this organ
      provides the necessary input to the brain for coordinating the initiation,
      modulation and end stages of engulfment, a paradigm that is consistent with
      unsteady hydrodynamic models and tag data from lunge-feeding rorquals. Despite
      the antiquity of unfused jaws in baleen whales since the late Oligocene (~23-28
      million years ago), this organ represents an evolutionary novelty for rorquals,
      based on its absence in all other lineages of extant baleen whales. This
      innovation has a fundamental role in one of the most extreme feeding methods in
      aquatic vertebrates, which facilitated the evolution of the largest vertebrates
      ever.

PMID- 22622578
TI  - Melanoma genome sequencing reveals frequent PREX2 mutations.
AB  - Melanoma is notable for its metastatic propensity, lethality in the advanced
      setting and association with ultraviolet exposure early in life. To obtain a
      comprehensive genomic view of melanoma in humans, we sequenced the genomes of 25
      metastatic melanomas and matched germline DNA. A wide range of point mutation
      rates was observed: lowest in melanomas whose primaries arose on non-ultraviolet
      exposed hairless skin of the extremities (3 and 14 per megabase (Mb) of genome),
      intermediate in those originating from hair-bearing skin of the trunk (5-55 per
      Mb), and highest in a patient with a documented history of chronic sun exposure
      (111 per Mb). Analysis of whole-genome sequence data identified PREX2
      (phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2)--a
      PTEN-interacting protein and negative regulator of PTEN in breast cancer--as a
      significantly mutated gene with a mutation frequency of approximately 14% in an
      independent extension cohort of 107 human melanomas. PREX2 mutations are
      biologically relevant, as ectopic expression of mutant PREX2 accelerated tumour
      formation of immortalized human melanocytes in vivo. Thus, whole-genome
      sequencing of human melanoma tumours revealed genomic evidence of ultraviolet
      pathogenesis and discovered a new recurrently mutated gene in melanoma.

PMID- 22622579
TI  - Sustained translational repression by eIF2alpha-P mediates prion
      neurodegeneration.
AB  - The mechanisms leading to neuronal death in neurodegenerative disease are poorly
      understood. Many of these disorders, including Alzheimer's, Parkinson's and prion
      diseases, are associated with the accumulation of misfolded disease-specific
      proteins. The unfolded protein response is a protective cellular mechanism
      triggered by rising levels of misfolded proteins. One arm of this pathway results
      in the transient shutdown of protein translation, through phosphorylation of the
      alpha-subunit of eukaryotic translation initiation factor, eIF2. Activation of
      the unfolded protein response and/or increased eIF2alpha-P levels are seen in
      patients with Alzheimer's, Parkinson's and prion diseases, but how this links to
      neurodegeneration is unknown. Here we show that accumulation of prion protein
      during prion replication causes persistent translational repression of global
      protein synthesis by eIF2alpha-P, associated with synaptic failure and neuronal
      loss in prion-diseased mice. Further, we show that promoting translational
      recovery in hippocampi of prion-infected mice is neuroprotective. Overexpression
      of GADD34, a specific eIF2alpha-P phosphatase, as well as reduction of levels of
      prion protein by lentivirally mediated RNA interference, reduced eIF2alpha-P
      levels. As a result, both approaches restored vital translation rates during
      prion disease, rescuing synaptic deficits and neuronal loss, thereby
      significantly increasing survival. In contrast, salubrinal, an inhibitor of
      eIF2alpha-P dephosphorylation, increased eIF2alpha-P levels, exacerbating
      neurotoxicity and significantly reducing survival in prion-diseased mice. Given
      the prevalence of protein misfolding and activation of the unfolded protein
      response in several neurodegenerative diseases, our results suggest that
      manipulation of common pathways such as translational control, rather than
      disease-specific approaches, may lead to new therapies preventing synaptic
      failure and neuronal loss across the spectrum of these disorders.

PMID- 22622580
TI  - Apolipoprotein E controls cerebrovascular integrity via cyclophilin A.
AB  - Human apolipoprotein E has three isoforms: APOE2, APOE3 and APOE4. APOE4 is a
      major genetic risk factor for Alzheimer's disease and is associated with Down's
      syndrome dementia and poor neurological outcome after traumatic brain injury and
      haemorrhage. Neurovascular dysfunction is present in normal APOE4 carriers and
      individuals with APOE4-associated disorders. In mice, lack of Apoe leads to blood
      brain barrier (BBB) breakdown, whereas APOE4 increases BBB susceptibility to
      injury. How APOE genotype affects brain microcirculation remains elusive. Using
      different APOE transgenic mice, including mice with ablation and/or inhibition of
      cyclophilin A (CypA), here we show that expression of APOE4 and lack of murine
      Apoe, but not APOE2 and APOE3, leads to BBB breakdown by activating a
      proinflammatory CypA-nuclear factor-kappaB-matrix-metalloproteinase-9 pathway in
      pericytes. This, in turn, leads to neuronal uptake of multiple blood-derived
      neurotoxic proteins, and microvascular and cerebral blood flow reductions. We
      show that the vascular defects in Apoe-deficient and APOE4-expressing mice
      precede neuronal dysfunction and can initiate neurodegenerative changes.
      Astrocyte-secreted APOE3, but not APOE4, suppressed the CypA-nuclear factor
      kappaB-matrix-metalloproteinase-9 pathway in pericytes through a lipoprotein
      receptor. Our data suggest that CypA is a key target for treating APOE4-mediated
      neurovascular injury and the resulting neuronal dysfunction and degeneration.

PMID- 22622581
TI  - Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity.
AB  - Oligodendrocytes, the myelin-forming glial cells of the central nervous system,
      maintain long-term axonal integrity. However, the underlying support mechanisms
      are not understood. Here we identify a metabolic component of axon-glia
      interactions by generating conditional Cox10 (protoheme IX farnesyltransferase)
      mutant mice, in which oligodendrocytes and Schwann cells fail to assemble stable
      mitochondrial cytochrome c oxidase (COX, also known as mitochondrial complex IV).
      In the peripheral nervous system, Cox10 conditional mutants exhibit severe
      neuropathy with dysmyelination, abnormal Remak bundles, muscle atrophy and
      paralysis. Notably, perturbing mitochondrial respiration did not cause glial cell
      death. In the adult central nervous system, we found no signs of demyelination,
      axonal degeneration or secondary inflammation. Unlike cultured oligodendrocytes,
      which are sensitive to COX inhibitors, post-myelination oligodendrocytes survive
      well in the absence of COX activity. More importantly, by in vivo magnetic
      resonance spectroscopy, brain lactate concentrations in mutants were increased
      compared with controls, but were detectable only in mice exposed to volatile
      anaesthetics. This indicates that aerobic glycolysis products derived from
      oligodendrocytes are rapidly metabolized within white matter tracts. Because
      myelinated axons can use lactate when energy-deprived, our findings suggest a
      model in which axon-glia metabolic coupling serves a physiological function.

PMID- 22622582
TI  - Cryptic peroxisomal targeting via alternative splicing and stop codon read
      through in fungi.
AB  - Peroxisomes are eukaryotic organelles important for the metabolism of long-chain
      fatty acids. Here we show that in numerous fungal species, several core enzymes
      of glycolysis, including glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and 3
      phosphoglycerate kinase (PGK), reside in both the cytoplasm and peroxisomes. We
      detected in these enzymes cryptic type 1 peroxisomal targeting signals (PTS1),
      which are activated by post-transcriptional processes. Notably, the molecular
      mechanisms that generate the peroxisomal isoforms vary considerably among
      different species. In the basidiomycete plant pathogen Ustilago maydis,
      peroxisomal targeting of Pgk1 results from ribosomal read-through, whereas
      alternative splicing generates the PTS1 of Gapdh. In the filamentous ascomycete
      Aspergillus nidulans, peroxisomal targeting of these enzymes is achieved by
      exactly the opposite mechanisms. We also detected PTS1 motifs in the glycolytic
      enzymes triose-phosphate isomerase and fructose-bisphosphate aldolase. U. maydis
      mutants lacking the peroxisomal isoforms of Gapdh or Pgk1 showed reduced
      virulence. In addition, mutational analysis suggests that GAPDH, together with
      other peroxisomal NADH-dependent dehydrogenases, has a role in redox homeostasis.
      Owing to its hidden nature, partial peroxisomal targeting of well-studied
      cytoplasmic enzymes has remained undetected. Thus, we anticipate that further
      bona fide cytoplasmic proteins exhibit similar dual targeting.

PMID- 22622583
TI  - The complex of tmRNA-SmpB and EF-G on translocating ribosomes.
AB  - Bacterial ribosomes stalled at the 3' end of malfunctioning messenger RNAs can be
      rescued by transfer-messenger RNA (tmRNA)-mediated trans-translation. The SmpB
      protein forms a complex with the tmRNA, and the transfer-RNA-like domain (TLD) of
      the tmRNA then enters the A site of the ribosome. Subsequently, the TLD-SmpB
      module is translocated to the P site, a process that is facilitated by the
      elongation factor EF-G, and translation is switched to the mRNA-like domain (MLD)
      of the tmRNA. Accurate loading of the MLD into the mRNA path is an unusual
      initiation mechanism. Despite various snapshots of different ribosome-tmRNA
      complexes at low to intermediate resolution, it is unclear how the large, highly
      structured tmRNA is translocated and how the MLD is loaded. Here we present a
      cryo-electron microscopy reconstruction of a fusidic-acid-stalled ribosomal 70S
      tmRNA-SmpB-EF-G complex (carrying both of the large ligands, that is, EF-G and
      tmRNA) at 8.3 A resolution. This post-translocational intermediate (TI(POST))
      presents the TLD-SmpB module in an intrasubunit ap/P hybrid site and a tRNA(fMet)
      in an intrasubunit pe/E hybrid site. Conformational changes in the ribosome and
      tmRNA occur in the intersubunit space and on the solvent side. The key underlying
      event is a unique extra-large swivel movement of the 30S head, which is crucial
      for both tmRNA-SmpB translocation and MLD loading, thereby coupling translocation
      to MLD loading. This mechanism exemplifies the versatile, dynamic nature of the
      ribosome, and it shows that the conformational modes of the ribosome that
      normally drive canonical translation can also be used in a modified form to
      facilitate more complex tasks in specialized non-canonical pathways.

PMID- 22622584
TI  - Evolution of the chalcone-isomerase fold from fatty-acid binding to
      stereospecific catalysis.
AB  - Specialized metabolic enzymes biosynthesize chemicals of ecological importance,
      often sharing a pedigree with primary metabolic enzymes. However, the lineage of
      the enzyme chalcone isomerase (CHI) remained unknown. In vascular plants, CHI
      catalysed conversion of chalcones to chiral (S)-flavanones is a committed step in
      the production of plant flavonoids, compounds that contribute to attraction,
      defence and development. CHI operates near the diffusion limit with
      stereospecific control. Although associated primarily with plants, the CHI fold
      occurs in several other eukaryotic lineages and in some bacteria. Here we report
      crystal structures, ligand-binding properties and in vivo functional
      characterization of a non-catalytic CHI-fold family from plants. Arabidopsis
      thaliana contains five actively transcribed genes encoding CHI-fold proteins,
      three of which additionally encode amino-terminal chloroplast-transit sequences.
      These three CHI-fold proteins localize to plastids, the site of de novo fatty
      acid biosynthesis in plant cells. Furthermore, their expression profiles
      correlate with those of core fatty-acid biosynthetic enzymes, with maximal
      expression occurring in seeds and coinciding with increased fatty-acid storage in
      the developing embryo. In vitro, these proteins are fatty-acid-binding proteins
      (FAPs). FAP knockout A. thaliana plants show elevated alpha-linolenic acid levels
      and marked reproductive defects, including aberrant seed formation. Notably, the
      FAP discovery defines the adaptive evolution of a stereospecific and
      catalytically 'perfected' enzyme from a non-enzymatic ancestor over a defined
      period of plant evolution.

PMID- 22622587
TI  - New evidence on testosterone and cooperation.

PMID- 22622589
TI  - Asymmetric hydrogenation of imines with a recyclable chiral frustrated Lewis pair
      catalyst.
AB  - A camphor based chiral phosphonium hydrido borate zwitterion was synthesised and
      successfully applied in the enantioselective hydrogenation of imines with
      selectivities up to 76% ee. The high stability of the novel chiral FLP-system
      enables effective recycling of the metal-free catalyst.

PMID- 22622591
TI  - Detection and care of familial hypercholesterolaemia in the community: is there a
      role for the pharmacist?
AB  - Familial hypercholesterolaemia (FH) is a dominantly inherited disorder present
      from birth that causes marked elevation in plasma cholesterol and premature
      coronary heart disease. It is estimated that there are at 40 million people with
      FH worldwide, but most remain unrecognised and inadequately treated. To bridge
      this gap in coronary prevention several guidelines on detecting and managing FH
      have been published. We briefly review these and comment on the potential role of
      pharmacists in case detection, point-of-care testing and pharmacotherapy.

PMID- 22622590
TI  - Effects of short-term addition of NSAID to diuretics and/or RAAS-inhibitors on
      blood pressure and renal function.
AB  - BACKGROUND: The combined post-operative use of diuretics and/or renin-angiotensin
      aldosterone system (RAAS) inhibitors may increase the risk of nonsteroidal anti
      inflammatory drug (NSAID) associated renal failure because of a drug-drug
      interaction. OBJECTIVE: The aim of this study was to investigate the effect of
      the short-term (<4 days) post-operative combined use of NSAIDs with diuretics
      and/or RAAS inhibitors on renal function and blood pressure. SETTING: One
      teaching hospital in the Netherlands. METHOD: The study-design was a prospective,
      observational cohort-study. Based on postoperative treatment with NSAIDs, the
      intervention-group was compared to a control-group (no NSAIDs treatment). MAIN
      OUTCOME MEASURE: Systolic blood pressure and renal function expressed by the
      estimated glomular filtration rate (eGFR) calculated with the modification of
      renal desease formula. RESULTS: 97 patients were included in the intervention
      group, 53 patients in the control-group. Patient characteristics were comparable
      except for one variable: 'combined use of a diuretic with a RAAS inhibitor' which
      was higher in the control-group (62 vs. 43 %, p = 0.046). Odds ratio for
      clinically relevant increase in systolic blood pressure was 0.66 (CI95 % 0.3
      1.5). Odds ratio for clinical relevant decrease in renal function was 2.44 (CI95
      % 1.1-5.2). On day 4 eGFR of 3 patients in the intervention- and 1 in the control
      group was <50 ml/min/1.73 m(2). CONCLUSION: Odds ratios showed no significant
      difference of a clinically relevant increase in systolic blood pressure but
      showed a higher risk for a clinically relevant decrease in renal function in the
      intervention group. However this decrease resulted in a relevant impaired renal
      function (<50 ml/min/1.73 m(2)) in only 3 patients in the interventiongroup and 1
      patient in the control-group. In the post-operative patient, without preexisting
      impaired renal function, concurrent diuretics and/or renin-angiotensinaldosterone
      system inhibitor therapy can be combined with short-term NSAID treatment.

PMID- 22622592
TI  - Successful treatment of sick sinus syndrome with Traditional Chinese Medicine.
AB  - BACKGROUND: Sick sinus syndrome comprises a variety of conditions involving sinus
      node dysfunction and commonly affects elderly persons. When patients have
      contraindications or refuse to receive pacemaker therapy, the alternative
      treatment could be considered. CASE DESCRIPTION: A 36-year-old male of sick sinus
      syndrome successfully treated with Traditional Chinese Medicine (TCM) was
      reported. This patient refused permanent pacemaker implantation for personal
      reasons. Traditional Chinese Medicine, Sumailing Koufuye, was employed. After 1
      day administration, the patients recovered significantly, both in manifestations
      and Holter Holter monitor. CONCLUSION: TCM showed therapeutic effects for early
      stage of sick sinus syndrome and could be promising alternative treatment.

PMID- 22622593
TI  - Evaluation of potentially inappropriate medications among older residents of
      Malaysian nursing homes.
AB  - BACKGROUND: There is an increasing evidence of medicines related issues such as
      inappropriate prescribing among older people. Inappropriate prescribing is an
      important risk factor for adverse drug reactions and hospitalizations in the
      older people. OBJECTIVE: To assess and characterize the prevalence of Potentially
      Inappropriate Medications (PIMs) in nursing home care in Malaysia as defined by
      Screening Tool of Older Peoples Prescriptions (STOPP) and Beers criteria.
      SETTING: Four Nursing Homes situated in Penang, Malaysia. METHODS: A multicenter
      and cross-sectional study was conducted over 2 months period at four large non
      governmental organizations nursing homes in Penang, Malaysia. The study
      population included older residents (>=65 years old) taking at least one
      medication. Residents who had been diagnosed with dementia or taking anti
      dementia drugs, delirium, too frail or refused to give consent were excluded.
      Demographic, clinical data and concurrent medications were collected through
      direct interview and also by reviewing medical records. STOPP and Beers criteria
      were applied in the medical review to screen for PIMs. MAIN OUTCOME MEASURE:
      Potentially Inappropriate Medication using STOPP and Beers criteria. RESULTS: Two
      hundred eleven residents were included in the study with the median age of 77
      (inter quartile range (IQR) 72-82) years. Median number of prescription medicines
      was 4 (IQR 1-14). STOPP identified less residents (50 residents, 23.7 %) being
      prescribed on PIMs compared with Beers criteria (69 residents, 32.7 %) (p <
      0.001). There was a significant difference in the number of residents with PIMs
      detected by STOPP (23.7 %) and by Beers criteria (32.7 %), p < 0.001. The common
      identified PIMs by Beers criteria included nifedipine short acting,
      chlorpheniramine and diphenhydramine. The STOPP identified first generation
      antihistamines, duplication of drug classes, glibenclamide and anticholinergic
      agents. Higher number of medications (OR = 1.405 [1.193-1.654]; OR = 1.447 [1.215
      1.723]) and longer stay at nursing home (OR = 1.132 [1.045-1.226]; OR = 1.133
      [1.034-1.241]) were identified as predictors for both Beers and STOPP PIMs.
      CONCLUSION: Potentially inappropriate medications are highly prevalent among
      older residents living in the nursing homes and are associated with number of
      medications and longer nursing home stay. Further research is warranted to study
      the impact of PIMs towards health related outcomes in these elderly.

PMID- 22622595
TI  - Synthesis of pyrido[2,3-b]indoles and pyrimidoindoles via Pd-catalyzed amidation
      and cyclization.
AB  - Biologically and pharmaceutically active core structures containing a new class
      of 4-hydroxy-alpha-carbolines, dihydropyrido[2,3-b]indoles, pyrimido[4,5-b] and
      [5,4-b]indoles have been synthesized in good yields via Pd-catalyzed amidation
      and cyclizations. The keto-enol tautomerism in 4-hydroxy-alpha-carbolines has
      been investigated by DFT calculations and spectroscopic techniques. The
      fluorescence studies of pyrimido[4,5-b] and [5,4-b]indoles were carried out with
      good quantum yields.

PMID- 22622594
TI  - Does good clinical practice at the primary care improve the outcome care for
      diabetic patients? Gender differences.
AB  - BACKGROUND: The Middle East region is predicted to have one of the highest
      prevalence of diabetes mellitus (DM) in the world. This is the first study in the
      region to assess treatment outcome of DM according to gender. OBJECTIVE: To
      assess the quality and effectiveness of diabetes care provided to patients
      attending primary care settings according to gender in the State of Qatar.
      DESIGN: It is an observational cohort study. SETTING: The survey was carried out
      in primary health care (PHC) centers in the State of Qatar. SUBJECTS AND METHODS:
      The study was conducted from January 2010 to August 2010 among diabetic patients
      attending (PHC) centers. Of the 2334 registered with diagnosed diabetes, 1705
      agreed and gave their consent to take part in this study, thus giving a response
      rate of 73.1%. Face to face interviews were conducted using a structured
      questionnaire including socio-demographic, clinical and satisfaction score of the
      patients. RESULTS: Majority of subjects were diagnosed with type 2 DM (84.9%). A
      significantly larger proportion of females with DM were divorced or widowed
      (9.1%) in comparison to males with DM (3.4%; p<0.001). A significantly larger
      proportion of females were overweight (46.5%; p=0.009) and obese (29.5%; p=0.003)
      in comparison to males. Males reported significantly greater improvements in mean
      values of blood glucose (mmol/l) (-2.11 vs. -0.66; p=0.007), HbA1c (%) (-1.44 vs.
      -0.25; p=0.006), cholesterol (mmol/l) (-0.16 vs. 0.12; p=0.053) and systolic
      blood pressure (mmHg) (-9.04 vs. -6.62; p<0.001) in comparison to females. While
      there was a remarkable increase in male patients with normal range of fasting
      blood glucose (FBG; 51.6%) as compared to the FBG measurement 1 year before
      (28.5%: p<0.001) there was only a slight increase in females normal range FBG
      during this period from 28.0% to 30.4% (p=0.357). CONCLUSION: The present study
      revealed that the current form of PHC centers afforded to diabetic patients
      provided significantly improved outcomes for males, but only minor improved
      outcomes for females. This study reinforces calls for a gender-specific approach
      to diabetes care.

PMID- 22622596
TI  - A critical appraisal of the recommendations for the use of meningococcal
      conjugate vaccines.
AB  - OBJECTIVES: To assess the epidemiology of meningococcal disease (MD) in Brazil
      and the impact that recent evidence and lessons learned from the introduction of
      meningococcal C conjugate (MCC) vaccines into immunization programs may have on
      different strategies of vaccine use. SOURCES: Non-systematic review of the
      MEDLINE, SciELO and LILACS databases covering the period from 2000 to 2011.
      SUMMARY OF THE FINDINGS: Meningococcal disease is endemic in Brazil, with
      periodic occurrence of outbreaks. Most cases are associated with serogroup C and
      the highest incidence rates are observed in infants, encouraging the introduction
      of MCC vaccine in the National Immunization Program in 2010 for children under 2
      years old. The introduction of MCC vaccines into immunization programs in Europe,
      Canada and Australia proved to be effective, with dramatic reduction in the
      incidence of serogroup C meningococcal disease, not only in the vaccinated, but
      also in the unvaccinated individuals. Long-term effectiveness of MCC vaccines was
      dependent on a combination of antibody persistence, immunologic memory and herd
      protection. Recent evidence indicating that antibody persistence is not long
      lasting in young immunized children, and that immunologic memory is not fast
      enough to protect them against the disease, emphasize the importance of herd
      protection to maintain the population protected. CONCLUSIONS: The rapid decline
      of antibody titers in children vaccinated in the first years of life suggests the
      need to incorporate booster doses before adolescence, especially in locations
      like Brazil, where the immunization program did not incorporate catch-up
      campaigns including adolescents, lacking the herd immunity effect.

PMID- 22622597
TI  - Photosensitizer-incorporated G-quadruplex DNA-functionalized magnetofluorescent
      nanoparticles for targeted magnetic resonance/fluorescence multimodal imaging and
      subsequent photodynamic therapy of cancer.
AB  - A smart heteronanostructure has been constructed for targeted photodynamic
      therapy and magnetic fluorescent imaging of cancer cells using photosensitizer
      incorporated G-quadruplex DNA functionalized magnetic nanoparticles.

PMID- 22622598
TI  - The Chicago Parent Program: comparing 1-year outcomes for African American and
      Latino parents of young children.
AB  - Data were merged from two prevention randomized trials testing 1-year outcomes of
      a parenting skills program, the Chicago Parent Program (CPP) and comparing its
      effects for African-American (n = 291) versus Latino (n = 213) parents and their
      preschool children. Compared to controls, intervention parents had improved self
      efficacy, used less corporal punishment and more consistent discipline, and
      demonstrated more positive parenting. Intervention children had greater
      reductions in behavior problems based on parent-report, teacher-report, and
      observation. Although improvements from the CPP were evident for parents in both
      racial/ethnic groups, Latino parents reported greater improvements in their
      children's behavior and in parenting self-efficacy but exhibited greater
      decreases in praise. Findings support the efficacy of the CPP for African
      American and Latino parents and young children from low-income urban communities.

PMID- 22622599
TI  - Medulloblastoma.
AB  - OPINION STATEMENT: The mainstay of medulloblastoma treatment is high-quality
      interdisciplinary collaboration in diagnosis, treatment, and aftercare by all
      involved disciplines. The first step in treatment of medulloblastoma is a maximal
      safe surgery, followed by thorough staging. Surgery should only be performed in
      experienced neurosurgical centers, with age-appropriate postoperative care. As
      optimal risk stratification is based on histopathological and neuroradiological
      assessments, these should be performed or confirmed by experienced specialists.
      Central review of histopathological subtype, as well as review of staging
      evaluations is highly desirable. For young children with desmoplastic/nodular
      (DMB), or extensive nodular medulloblastoma, craniospinal or any radiotherapy
      should be avoided. For young children with classic medulloblastoma (CMB), large
      cell, or anaplastic medulloblastoma (LC/A MB) optimized strategies with high-dose
      chemotherapy and autologous stem cell rescue with or without local radiotherapy
      are under investigation. For older clinical standard risk patients (without
      metastases, without postoperative residual tumor >1.5 cm(2)) with CMB or DMB,
      craniospinal radiotherapy with 23.4 Gy and boost to the posterior fossa to 54 Gy,
      followed by maintenance chemotherapy can be regarded as a standard therapy
      besides other currently applied regimen, such as the use of intensified
      chemotherapy after irradiation. Older children with LC/A MB, metastatic
      medulloblastoma, and/or large residual tumor can be regarded as high-risk
      patients and should receive intensified treatment: intensified chemotherapeutic
      regimen before or after radiotherapy with increased dose (36-Gy CSI
      normofractionated, or 40-Gy hyperfractionated) is used. For treatment to be
      effective, quality control of radiotherapy is of high relevance. Information on
      long-term sequelae is essential and appropriate multidisciplinary follow-up and
      support, including rehabilitation and help for reintegration, is necessary.
      Whenever possible, patients should be included in prospective studies, and tumor
      material should be sampled to facilitate further research on medulloblastoma
      biology, which will significantly influence the stratification criteria and the
      introduction of targeted therapies in standard treatment recommendations in the
      future.

PMID- 22622600
TI  - Unfavourable outcome of deep brain stimulation in a Tourette patient with severe
      comorbidity.

PMID- 22622601
TI  - Different approaches for complete mobilization of the splenic flexure during
      laparoscopic rectal cancer resection.
AB  - PURPOSE: Laparoscopic resection of rectal cancer has already become the standard
      procedure in many hospitals. The splenic flexure mobilization (SFM) is an
      important preparational step. Several methods are used for laparoscopic SFM;
      however, studies comparing different approaches are lacking. In the present
      study, three different approaches for SFM have been compared to each other.
      METHODS: Between January 1998 and December 2010, 415 patients with rectal
      adenocarcinoma underwent laparoscopic rectal resection at one center. Of these,
      303 patients received complete splenic flexure mobilization. The SFM was
      performed using either a medial (SFM-M; n = 41), lateral (SFM-L; n = 214), or
      anterior (SFM-A; n = 48) approach. RESULTS: There was a significantly higher rate
      of intraoperative complications in the SFM-L group as compared to the SFM-M or
      the SFM-A group (p = 0.038). Postoperative surgical complications occurred in 5
      (10.6 %) patients of the SFM-A group compared to 38 patients (17.7 %) in the SFM
      L group (p = 0.002) and 5 (12.1 %) patients in the SFM-M group (p = 0.037). SFM-L
      was also associated with a higher frequency of overall postoperative morbidity
      which was mainly due to wound infection rates (p = 0.001). CONCLUSIONS: The
      anterior approach for SFM in laparoscopic surgery seems to be associated with
      lower frequency of intra- and postoperative morbidity.

PMID- 22622603
TI  - Strong values, strength in practice.

PMID- 22622602
TI  - Does body mass index impact the number of LNs harvested and influence long-term
      survival rate in patients with stage III colon cancer?
AB  - BACKGROUND: The aim of this study is to evaluate whether different body mass
      index (BMI) values affect lymph node (LN) retrieval and whether such variations
      influence long-term survival in Asian patients. METHOD: From January 1995 to July
      2003, 645 stage III colon cancer patients were enrolled in our study. Patients
      were stratified into four groups: Obese (BMI ? 27 kg/m(2)), overweight (24 <= BMI
      < 27 kg/m(2)), normal (18.5 <= BMI < 24 kg/m(2)), and underweight (BMI < 18.5
      kg/m(2)). RESULTS: Mean BMI in the cohort was 23.3 kg/m(2). Mean number of LNs
      harvested was 23.1, 19.5, 19.8 and 28.1 in the normal, overweight, obese and
      underweight groups, respectively. There was a significant difference in the mean
      number of LNs harvested when comparing the overweight and underweight groups to
      the normal group (p = 0.013 and p = 0.04, respectively). Females were
      overrepresented in the underweight group (p = 0.011), and patients who had
      proximal colon cancers were more frequently underweight (p = 0.018). The mean
      number of LNs harvested varied by cases of right hemicolectomy (p = 0.009) and
      proximal cancer location (p = 0.009) for different BMI groups. Multivariate
      analysis showed that underweight, proximal colon cancer, well- or moderately
      differentiated adenocarcinoma and stage IIIC cancer were significant variables
      for adequate LN recovery. BMI was not significantly associated with relapse-free
      survival (p = 0.523) or overall survival (p = 0.127). CONCLUSION: BMI is
      associated with LN harvest but is not an independent variable in stage III colon
      cancer survival.

PMID- 22622604
TI  - Become a nurse author.

PMID- 22622605
TI  - Sustaining disease-specific performance improvement measures for joint
      replacement.
AB  - To maintain standards of excellence and continuously improve their outcomes,
      specialized joint replacement centers must develop, implement, and sustain
      specific performance improvement activities. This article describes the
      activities at one. Midwestern healthcare system's joint replacement center
      related to three disease-specific performance improvement measures: fall
      prevention, preoperative education, and pain management. Specific steps in the
      process for each measure are described. These include current-state analyses,
      goals established, the use of Plan-Do-Study-Act (PDSA) methodology to identify
      and implement appropriate interventions, and the use of the Six Sources of
      Influence model to promote successful change. Outcomes, lessons learned, and
      suggestions for replication by other institutions are discussed.

PMID- 22622607
TI  - Effectiveness of multimodal pain management protocol in total knee arthroplasty
      patients.
AB  - BACKGROUND: Numerous methods for postoperative pain management after total knee
      arthroplasty (TKA) are reported. Multimodal pain management approaches, including
      peripheral nerve blocks and systemic analgesia, have been shown to decrease
      patient pain, increase patient satisfaction with pain control, decrease length of
      stay (LOS), and improve patient outcomes. PURPOSE/METHODS: To compare patient
      outcomes (pain scores, LOS, postoperative nausea and vomiting, and movement)
      between 66 TKA patients of a single orthopaedic surgeon in 2010 who received a
      multimodal approach to 45 historical (control) patients in 2009 who did not
      receive a multimodal pain management protocol. RESULTS: Patients who were treated
      with the multimodal pain protocol had significantly lower pain scores in the
      immediate postoperative period, less postoperative nausea and vomiting day of
      surgery, and a decrease in LOS by half a day despite increased buckling and
      increased level of assistance with ambulation. CONCLUSION: The multimodal pain
      approach improved patient outcomes in TKA patients.

PMID- 22622608
TI  - Glucosamine and chondroitin: an appropriate adjunct treatment of symptomatic
      osteoarthritis of the knee.
AB  - Osteoarthritis (OA) is a leading cause of disability in the United States.
      Current treatment focuses on symptom relief and improving a patient's overall
      function. Pharmacological treatments aim to correct symptomatic complaints as
      well as structural problems in OA. Glucosamine (sulfate or hydrochloride) and
      chondroitin sulfate have been linked as an optional treatment in OA for several
      years. There is controversy, however, surrounding their use and efficacy. The
      American Academy of Orthopaedic Surgeons published clinical practice guidelines
      in 2008 that recommended against the use of glucosamine and chondroitin sulfate
      (p. ii). Despite conflicting results on the degree of efficacy, the most current
      research suggested that glucosamine and chondroitin sulfate have the potential to
      provide pain-relieving benefits as well as possibly decrease the effects of joint
      space narrowing. The purpose of this article was to document the most current
      research evidence on the use and efficacy of glucosamine and chondroitin sulfate
      supplements for patients with symptomatic OA of the knee as well as create an
      evidence-based, best practice educational tool describing a treatment algorithm
      for nurse practitioners treating a patient with symptomatic OA of the knee.

PMID- 22622610
TI  - Patient's perception of quality patient--provider communication.
AB  - PURPOSE: To develop a model of patients' perception of quality patient-healthcare
      provider communication. METHODS/SAMPLE: Fifteen patients with rheumatoid
      arthritis participated in in-depth, audiorecorded interviews. Following
      transcription verification, interviews were analyzed using constant comparative
      analysis to identify primary themes and develop a model of patients' perception
      of quality patient-healthcare provider communication. FINDINGS: The participants
      described a multifaceted, dynamic process of quality patient-healthcare provider
      communication involving the interrelationship between appropriate time and 4 key
      communication exchanges: patient honesty when explaining symptoms, patients
      asking questions and offering opinions, healthcare providers asking questions and
      offering opinions, and healthcare providers disseminating information.
      CONCLUSION: By understanding patient-healthcare provider communication from the
      patient perspective within the rubric of this model, healthcare providers can
      adapt interactions with patients with rheumatoid arthritis to incorporate
      dimensions of the exchange that their patients feel create effective
      communication.

PMID- 22622611
TI  - Syndesmotic ankle sprain.
AB  - Ankle sprain injuries are the most common type of joint sprain. The prevalence of
      ankle joint sprains accounts for 21% of joint injuries in the body. Although
      somewhat rare, high-ankle or syndesmotic ankle sprains occur in up to 15% of
      ankle trauma. This article will present the pathomechanics of the high-ankle or
      syndesmotic sprain.

PMID- 22622613
TI  - The power of remodeling bones in children.

PMID- 22622614
TI  - Improving patient safety through improved communication and teamwork.

PMID- 22622617
TI  - Reducing lower leg amputations in diabetes: a challenge for patients, healthcare
      providers and the healthcare system.
AB  - Amputation of the lower limb is one of the most feared diabetic complications. It
      is associated with loss of mobility and a poor quality of life. Amputations
      result in high economic burden for the healthcare system. The financial cost is
      also high for patients and their families, particularly in countries that lack a
      comprehensive health service and/or have a low income. Losing a leg frequently
      implies financial ruin for a whole family in these countries; therefore, a
      reduction in diabetes-related amputations is a major global priority. Marked
      geographical variation in amputation rates has been reported within specific
      regions of an individual country and between countries. A coordinated healthcare
      system with a multidisciplinary approach is essential if the number of
      amputations is to be reduced. This commentary discusses how studies on the
      variation in amputation rates can help to identify barriers in the access or
      delivery of care with the aim of reducing the burden of diabetic foot disease.

PMID- 22622618
TI  - Gold nanorods in an oil-base formulation for transdermal treatment of type 1
      diabetes in mice.
AB  - Efficient transdermal insulin delivery to the systemic circulation would bring
      major benefit to diabetic patients. We investigated the possibility of using gold
      nanorods (GNRs) that formed a complex with an edible surfactant and insulin (INS)
      in an oil phase to form a solid-in-oil (SO) formulation (SO-INS-GNR) for
      transdermal treatment of diabetes. Diabetic mice comprised the model for our
      study. In vitro, there was high penetration of insulin through the stratum
      corneum (SC) and the dermis in mouse skin treated with an SO-INS-GNR complex plus
      near-infrared (NIR) light irradiation. Blood glucose levels in the diabetic mice
      were significantly decreased after treatment with SO-INS-GNR plus irradiation. To
      our knowledge, this is the first study to use gold nanorods for systemic insulin
      delivery through the skin. The use of an SO-INS-GNR complex combined with NIR
      irradiation may provide the possibility of transdermal insulin delivery to
      diabetic patients.

PMID- 22622619
TI  - Herpes simplex virus type 1 induces simultaneous activation of Toll-like
      receptors 2 and 4 and expression of the endogenous ligand serum amyloid A in
      astrocytes.
AB  - Herpes simplex virus type 1 (HSV-1) is the most common pathogenic cause of
      sporadic acute encephalitis and it produces latent persistent infection lifelong
      in infected individuals. Brain inflammation is associated with activation of
      glial cells, which can detect pathogen-associated molecular patterns (PAMPs)
      through a variety of pattern-recognition receptors (PRR), including Toll-like
      receptors (TLRs). In this study, we evaluated the expression and activation of
      TLR2, TLR3, and TLR4 in HSV-1-infected astrocyte and neuronal primary cultures.
      Our results showed a clear induction in TLR2 and TLR4 expression in astrocytes as
      early as 1 h after HSV-1 infection, whereas no significant change was observed in
      neurons. In addition, infected astrocytes showed increased levels of interferon
      regulatory factors IRF3 and IRF7, interferon beta (INFbeta), interleukin 6 (IL6),
      and serum amyloid A (SAA3) transcripts, as well as phospho-IRF3 protein. These
      effects seemed to be dependent on viral replication since previous treatment of
      the cells with acyclovir resulted in low levels of TLRs expression and activation
      even after 4 h post-infection. These results suggest that reactivation of HSV-1
      at the central nervous system (CNS) would likely induce and activate TLR2 and
      TLR4 receptors directly through interaction of astrocytes with the pathogen and
      also indirectly by endogenous ligands produced locally, such as serum amyloid
      protein, potentiating the neuroinflammatory response.

PMID- 22622620
TI  - Chemiluminescence excited photoelectrochemistry using graphene-quantum dots
      nanocomposite for biosensing.
AB  - Chemiluminescence was used as the exciting light source to construct a universal
      photoelectrochemical platform based on a reduced graphene oxide-CdS
      nanocomposite, which greatly improves the photovoltaic transfer efficiency and
      leads to excellent performance for the photoelectrochemical immunoassay.

PMID- 22622621
TI  - SAMPL3: blinded prediction of host-guest binding affinities, hydration free
      energies, and trypsin inhibitors.

PMID- 22622622
TI  - Notes on interval estimation of the gamma correlation under stratified random
      sampling.
AB  - We have developed four asymptotic interval estimators in closed forms for the
      gamma correlation under stratified random sampling, including the confidence
      interval based on the most commonly used weighted-least-squares (WLS) approach
      (CIWLS), the confidence interval calculated from the Mantel-Haenszel (MH) type
      estimator with the Fisher-type transformation (CIMHT), the confidence interval
      using the fundamental idea of Fieller's Theorem (CIFT) and the confidence
      interval derived from a monotonic function of the WLS estimator of Agresti's
      alpha with the logarithmic transformation (MWLSLR). To evaluate the finite-sample
      performance of these four interval estimators and note the possible loss of
      accuracy in application of both Wald's confidence interval and MWLSLR using
      pooled data without accounting for stratification, we employ Monte Carlo
      simulation. We use the data taken from a general social survey studying the
      association between the income level and job satisfaction with strata formed by
      genders in black Americans published elsewhere to illustrate the practical use of
      these interval estimators.

PMID- 22622623
TI  - Virgibacillus albus sp. nov., a novel moderately halophilic bacterium isolated
      from Lop Nur salt lake in Xinjiang province, China.
AB  - A Gram-positive, moderately halophilic, strictly aerobic bacterium, designated
      YIM 93624(T), was isolated from a salt lake in Xinjiang province of China and
      subjected to a polyphasic taxonomic study. Strain YIM 93624(T) grew at 15-45 
      degrees C (optimum 25-30  degrees C), 1-17% (w/v) NaCl (optimum 5-10 %, w/v) and
      pH 4.0-9.0 (optimum pH 7.0). The predominant menaquinone was found to be MK-7.
      The major fatty acids were anteiso-C(15:0) and C(16:0). The polar lipids
      consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol,
      a glycolipid and two unidentified phospholipids. The cell-wall peptidoglycan
      contained meso-diaminopimelic acid. The G+C content of the genomic DNA was 37.9
      mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain
      YIM 93624(T) was a member of the genus Virgibacillus and exhibited the highest
      similarity of 97.0 % to Virgibacillus koreensis KCTC 3823(T). However, the level
      of DNA-DNA relatedness between strain YIM 93624(T) and V. koreensis KCTC 3823(T)
      was 32.5 %. On the basis of phylogenetic, physiological and chemotaxonomic
      analysis data, the isolate is concluded to represent a novel species of the genus
      Virgibacillus, for which the name Virgibacillus albus sp. nov., is proposed, with
      type strain of YIM 93624(T) (=DSM 23711(T) = JCM 17364(T)).

PMID- 22622624
TI  - Comparative evaluation of three Lactobacilli with strain-specific activities for
      rats when supplied in drinking water.
AB  - To test the in vivo benefits of three lactobacilli and to compare their different
      efficacies based on strain-specific activities by using rats as an experimental
      model, a growth-promotion and a challenge trial were conducted. The three
      strains, Lactobacillus salivarius G1-1, Lactobacillus reuteri G22-2, and
      Lactobacillus reuteri G8-5 shared antimicrobial, bile-salt-hydrolase and
      amylolytic activities in vitro, respectively. In the 17 day growth-promotion
      trial, 48 rats were allotted to four treatments with 12 replicates per treatment:
      a control group, which received saline, as well as three experimental groups,
      which received 10(8) cells/ml of one of the three lactobacilli in saline
      suspension. The results showed that compared with the control group, L. reuteri
      G8-5 significantly improved feed efficiency and decreased fecal pH values on days
      8 and 17, concomitant with reduced faecal coliform counts on d 17 (p < 0.05). All
      treatments with lactobacilli caused an increase in the moisture content of the
      faeces and a decrease in the serum total cholesterol and blood urea nitrogen
      levels. High-density lipoprotein cholesterol was only elevated for rats which
      received L. reuteri G22-2. In the Salmonella-challenge trial, 40 rats were
      allotted to five treatments (8 replicates per treatment) which consisted of a
      positive control (infected, no Lactobacillus pretreatment), a negative control
      (uninfected, no Lactobacillus pretreatment) and three Lactobacillus-pretreated
      groups (10(9) cells/ml in saline). The results showed that rats in all
      Lactobacillus pretreated groups were protected from infection with significantly
      higher weight gain, feed intake and feed efficiency compared with positive
      control rats (p < 0.05). Rats treated with L. salivarius G1-1 and L. reuteri G22
      2 tended to exhibit higher weight gains than those pretreated with L. reuteri G8
      5. Significantly lower Salmonella shedding in faeces, Salmonella numbers in the
      spleen and the relative weight of the spleen were observed in the Lactobacillus
      groups (p < 0.05). Based on the overall results, it can be concluded that not all
      strains within the same lactobacilli species show similar effects and that some
      of the beneficial functionalities to animals were strain-specific. Therefore
      strains for practical application need to be carefully selected based on their
      strain-specific characters.

PMID- 22622626
TI  - Catalytic, enantio- and diastereoselective synthesis of gamma-butyrolactones
      incorporating quaternary stereocentres.
AB  - A new, highly enantio- and diastereoselective catalytic asymmetric formal
      cycloaddition of aryl succinic anhydrides and aldehydes which generates paraconic
      acid (gamma-butyrolactone) derivatives is reported.

PMID- 22622625
TI  - Fungal colonization in newborn babies of very low birth weight: a cohort study.
AB  - OBJECTIVES: To learn about the profile of fungal colonization and related risk
      factors in premature newborns. METHODS: Prospective cohort, from 04/01/2010 to
      04/31/2011, with 44 patients admitted to the neonatal intensive care unit, born
      at the hospital maternity, weighing less than 1,500 g. On admission, data were
      collected on pre-natal care and childbirth. Clinical and laboratory information,
      nasal and rectal swabs, and peripheral blood cultures were collected on days 1,
      7, 10, and 14 of stay in neonatal intensive care unit and then every 7 days until
      discharge or death. For statistical analysis, we used the chi-square test, Fisher
      exact test, Kaplan-Meier and logistic regression model. RESULTS: The incidence of
      colonization was 13.5/1,000 patients/day. The incidence of candidemia was
      0.9/1,000 patients/day. The average hospitalization time was 30.5 days (+/-
      20.27), and the onset of colonization occurred, in average, at 11.13 days (+/-
      8.82). Vaginal delivery was found to be an independent risk factor for the
      development of fungal colonization during hospitalization (p = 0.042, odds ratio
      = 4.38, 95% confidence interval [95%CI] = 1,13-16,99). Likewise, leukocytosis (>
      30,000/mm3) on admission was an indicator for the simultaneous presence of fungal
      colonization (p = 0.048). The presence of bronchopulmonary dysplasia tends to be
      a factor of higher probability for the development of colonization (p = 0.067).
      The most affected colonization site was the rectal mucosa: 89.09 versus 10.9% of
      the nasal mucosa. CONCLUSIONS: Vaginal delivery and leukocytosis over 30,000/mm3
      on admission were found to be risk factors for fungal colonization during
      hospitalization.

PMID- 22622627
TI  - Developing the Chinese version of the new 5-level EQ-5D descriptive system: the
      response scaling approach.
AB  - PURPOSE: To develop a Chinese version of the new, 5-level EQ-5D descriptive
      system (EQ-5D-5L) from the existing EQ-5D-3L by identifying Chinese label wording
      suitable for constructing EQ-5D-5L's 5-point response scales. METHODS: In face-to
      face interviews, perceived severity of selected Chinese labels when they were
      used to describe EQ-5D health problems was measured from 50 native Chinese
      speakers using a 0 (no problems) to 100 (the worst problems) visual analog scale.
      Selection of label wording was based on the severity scores and semantic
      similarity with label wording used in the existing English and Spanish EQ-5D-5L.
      RESULTS: The severity scores supported the use of Chinese wording of 'only a
      little' (range of median: 12.5-17), 'moderate' (range of median: 50-53), and
      'severe' (range of median: 82.5-90) as the descriptors for the intermediate
      functional levels of the five EQ-5D dimensions and the label wording of 'very
      severe' (median: 90) to describe the worst level of pain/discomfort and
      anxiety/depression. CONCLUSIONS: The Chinese version of the EQ-5D-5L comprises
      descriptors with similar interpretations as those used its English and Spanish
      counterparts. The response scaling exercise is a useful method for cross-cultural
      adaptation of health-status instruments.

PMID- 22622628
TI  - Anxiety and methylphenidate in attention deficit hyperactivity disorder: a double
      blind placebo-drug trial.
AB  - To examine the relationship between attention and anxiety and the response to
      methylphenidate in children with attention deficit hyperactivity disorder (ADHD),
      a total of 57 boys, between the ages of 7-12 years, were assessed for their
      attention and level of anxiety. Methylphenidate was administered for a week in a
      randomized double-blind drug/placebo-drug cross-over design. The levels of
      anxiety were evenly distributed between the inattentive and hyperactive/impulsive
      types. Anxiety was significantly correlated with the attention as reported by
      both teachers and parents. The response to methylphenidate was inversely
      correlated with the reported anxiety level only in boys with the
      hyperactive/impulsive and combined types. The higher the level of anxiety, the
      lower level of response to methylphenidate was observed. In the assessment and
      treatment of children with ADHD, the level of anxiety should be evaluated and
      taken into account while planning and monitoring treatment regiment.

PMID- 22622629
TI  - Terpyridine-fused polyaromatic hydrocarbons generated via cyclodehydrogenation
      and used as ligands in Ru(II) complexes.
AB  - A series of novel fused 4'-substituted 2,2' : 6',2''-terpyridine ligands and
      their ruthenium(II) complexes were prepared. The unusual 4'-substituents
      comprised 2,3,4,5-pentaphenylbenzene and its tert-butyl derivative (1 and 2) and
      the products from oxidative cyclodehydrogenation, i.e. polyaromatic fragments
      consisting of ten or thirteen fused benzene rings (3 and 4). The syntheses of all
      the ligands are discussed in terms of the demands and limitations of the Scholl
      reaction. The optical properties of the ligands, along with the single-crystal X
      ray structures of 1 and 2, are presented. The latter show that the
      pentaphenylbenzene and terpyridine appendages of 1 and 2 are perpendicular in the
      solid state. Despite the inclusion of the large organic chromophore the
      absorption and emission properties of the Ru(II) bis-terpy complexes (of ligands
      1, 2 and 3) were found to be comparable to those of [Ru(terpy)(2)](2+). They are
      non-emissive at room temperature but emit at 77 K with excited state lifetimes of
      11-12 MUs.

PMID- 22622634
TI  - Therapeutics: iterations of BRAF.

PMID- 22622640
TI  - Metastasis: dynamic interactions.

PMID- 22622642
TI  - In silico analyses of COMT, an important signaling cascade of dopaminergic
      neurotransmission pathway, for drug development of Parkinson's disease.
AB  - Catechol-O-methyltransferase (COMT) has a vital role for degradation of dopamine,
      a neurotransmitter, and this dopamine performs an important function in our
      mental and physical health. The scarcity of dopamine may lead to Parkinson's
      disease, and inhibition of COMT can stop dopamine metabolism. Here, we have
      carried out genomics and proteomics analyses of COMT in order to facilitate new
      inhibitors of COMT. For genomics analyses, we performed codon composition
      investigation of COMT gene which shows A+T content which is 53.3 %. For
      proteomics analyses, conservation patterns and residues (highly conserved amino
      acids GLU64, LEU65, GLY66, CYS69, GLY70, ALA77, GLU90, THR99, SER119, ASP136,
      LEU140, ASP141, THR164, ASN170, VAL171, and ILE172), binding grooves, binding
      pockets, binding and conformation with substrate, evaluation of amino acid
      composition (15 % leucine rich), high scoring hydrophobic segments, high scoring
      transmembrane segments, tandem and periodic repeats, and disulfide bonds (three
      numbers), sequence logos (maximum stack height of 3 b and minimum stack height of
      <0.5 b) have been investigated for COMT protein. Furthermore, using COMT
      sequences of different species (class Mammalia, class Amphibia, and class
      Pisces), a phylogenetic tree has been constructed to examine the evolutionary
      relationship among different species.

PMID- 22622643
TI  - The anticancer activity and HSA binding properties of the structurally related
      platinum (II) complexes.
AB  - The development of resistance and unwanted harmful interaction with other
      biomolecules instead of DNA are the major drawbacks for application of platinum
      (Pt) complexes in cancer chemotherapy. To conquer these problems, much works have
      been done so far to discover innovative Pt complexes. The objective of the
      current study was to evaluate the anti cancer activities of a series of four and
      five-coordinated Pt(II) complexes, having deprotonated 2-phenyl pyridine
      (abbreviated as C^N), biphosphine moieties, i.e., dppm = bis(diphenylphosphino)
      methane (Ph(2)PCH(2)PPh(2)) and dppa = bis(diphenylphosphino)amine
      (Ph(2)PNHPPh(2)), as the non-leaving carrier groups. The growth inhibitory effect
      of the Pt complexes [Pt(C^N)(dppm)]PF(6): C(1), [Pt(C^N)(dppa)]PF(6): C(2), and
      [Pt(C^N)I(dppa)]: C(3), toward the cancer cell lines was measured using 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. In addition, the
      florescence quenching experiments of the interaction between human serum albumin
      (HSA) and the Pt complexes were performed in order to obtain the binding
      parameters and to evaluate the denaturing properties of these complexes upon
      binding to the general carrier protein of blood stream. The structure-activity
      relationship studies reveal that four-coordinated Pt complexes C(1) and C(2) with
      both significant hydrophobic and charge characteristics, not only exhibit strong
      antiproliferation activity toward the cancer cell lines, but also they display
      lower denaturing effect against carrier protein HSA. On the other hand, five
      coordinated C(3) complex with the unusual intermolecular NH...Pt hydrogen binding
      and the intrinsic ability for oligomerization, exhibits poor anticancer activity
      and strong denaturing property. The current study reveals that the balance
      between charge and hydrophobicity of the Pt complexes, also their hydrogen
      binding abilities and coordination mode are important for their anticancer
      activities. Moreover, this study may suggest C(1) and C(2) as the potential
      template structures for synthesis of new generation of four-coordinated Pt
      complexes with strong anticancer activities and weak denaturing effects against
      proteins.

PMID- 22622644
TI  - Cross-linked enzyme aggregates of phenylalanine ammonia lyase: novel biocatalysts
      for synthesis of L-phenylalanine.
AB  - Cross-linked enzyme aggregates of phenylalanine ammonia lyase (PAL-CLEAs) from
      Rhodotorula glutinis were prepared. The effects of the type of aggregating agent,
      its concentration, and that of cross-linking agent were studied. PAL-CLEAs
      production was most effective using ammonium sulfate (40 % saturation), followed
      by cross-linking for 1 h with 0.2 % (v/v) glutaraldehyde. Moreover, the storage
      and operational stability of the resulting PAL-CLEAs were also investigated.
      Compared to the free enzyme, the PAL-CLEAs exhibited the expected increased
      stability of the enzyme against various deactivating conditions such as pH,
      temperature, denaturants, and organic solvents and showed higher storage
      stability than its soluble counterpart. Additionally, the reusability of PAL
      CLEAs with respect to the biotransformation of L-phenylalanine was evaluated. PAL
      CLEAs could be recycled at least for 12 consecutive batch reactions without
      dramatic activity loss, which should dramatically increase the commercial
      potential of PAL for synthesis of L: -phenylalanine. To the best of our
      knowledge, this is the first report of immobilization of PAL as cross-linked
      enzyme aggregates.

PMID- 22622641
TI  - Spatial regulation of receptor tyrosine kinases in development and cancer.
AB  - During development and tissue homeostasis, patterns of cellular organization,
      proliferation and movement are highly choreographed. Receptor tyrosine kinases
      (RTKs) have a crucial role in establishing these patterns. Individual cells and
      tissues exhibit tight spatial control of the RTKs that they express, enabling
      tissue morphogenesis and function, while preventing unwarranted cell division and
      migration that can contribute to tumorigenesis. Indeed, RTKs are deregulated in
      most human cancers and are a major focus of targeted therapeutics. A growing
      appreciation of the essential role of spatial RTK regulation during development
      prompts the realization that spatial deregulation of RTKs is likely to contribute
      broadly to cancer development and may affect the sensitivity and resistance of
      cancer to pharmacological RTK inhibitors.

PMID- 22622645
TI  - Cryopreservative effects of the recombinant ice-binding protein from the arctic
      yeast Leucosporidium sp. on red blood cells.
AB  - Antifreeze proteins (AFPs) have important functions in many freeze-tolerant
      organisms. The proteins non-colligatively lower the freezing point and
      functionally inhibit ice recrystallization in frozen solutions. In our previous
      studies, we found that the Arctic yeast Leucosporidium sp. produces an AFP
      (LeIBP), and that the protein could be successfully produced in Pichia expression
      system. The present study showed that recombinant LeIBP possesses the ability to
      reduce the damage induced to red blood cells (RBCs) by freeze thawing. In
      addition to 40 % glycerol, both 0.4 and 0.8 mg/ml LeIBPs significantly reduced
      freeze-thaw-induced hemolysis at either rapid- (45  degrees C) or slow-warming
      (22  degrees C) temperatures. Post-thaw cell counts of the cryopreserved RBCs
      were dramatically enhanced, in particular, in 0.8 mg/ml LeIBP. Interestingly, the
      cryopreserved cells in the presence of LeIBP showed preserved cell size
      distribution. These results indicate that the ability of LeIBP to inhibit ice
      recrystallization helps the RBCs avoid critically damaging electrolyte
      concentrations, which are known as solution effects. Considering all these data,
      LeIBP can be thought of as a key component in improving RBC cryopreservation
      efficiency.

PMID- 22622646
TI  - Desulfuribacillus alkaliarsenatis gen. nov. sp. nov., a deep-lineage, obligately
      anaerobic, dissimilatory sulfur and arsenate-reducing, haloalkaliphilic
      representative of the order Bacillales from soda lakes.
AB  - An anaerobic enrichment culture inoculated with a sample of sediments from soda
      lakes of the Kulunda Steppe with elemental sulfur as electron acceptor and
      formate as electron donor at pH 10 and moderate salinity inoculated with
      sediments from soda lakes in Kulunda Steppe (Altai, Russia) resulted in the
      domination of a Gram-positive, spore-forming bacterium strain AHT28. The isolate
      is an obligate anaerobe capable of respiratory growth using elemental sulfur,
      thiosulfate (incomplete reduction) and arsenate as electron acceptor with H2,
      formate, pyruvate and lactate as electron donor. Growth was possible within a pH
      range from 9 to 10.5 (optimum at pH 10) and a salt concentration at pH 10 from
      0.2 to 2 M total Na+ (optimum at 0.6 M). According to the phylogenetic analysis,
      strain AHT28 represents a deep independent lineage within the order Bacillales
      with a maximum of 90 % 16S rRNA gene similarity to its closest cultured
      representatives. On the basis of its distinct phenotype and phylogeny, the novel
      haloalkaliphilic anaerobe is suggested as a new genus and species,
      Desulfuribacillus alkaliarsenatis (type strain AHT28(T) = DSM24608(T) = UNIQEM
      U855(T)).

PMID- 22622647
TI  - Bacterial and archaeal diversity in two hot spring microbial mats from the
      geothermal region of Tengchong, China.
AB  - We investigated the bacterial and archaeal diversity in two hot spring microbial
      mats from the geothermal region of Tengchong in the Yunnan Province, China, using
      direct molecular analyses. The Langpu (LP) laminated mat was found by the side of
      a boiling pool with temperature of 60-65  degrees C and a pH of 8.5, while the
      Tengchong (TC) streamer mat consisted of white streamers in a slightly acidic (pH
      6.5) hot pool outflow with a temperature of 72  degrees C. Four 16S rRNA gene
      clone libraries were constructed and restriction enzyme analysis of the inserts
      was used to identify unique sequences and clone frequencies. From almost 200
      clones screened, 55 unique sequences were retrieved. Phylogenetic analysis showed
      that the LP mat consisted of a diverse bacterial population [Cyanobacteria,
      Chloroflexi, Chlorobia, Nitrospirae, 'Deinococcus-Thermus', Proteobacteria
      (alpha, beta and delta subdivisions), Firmicutes, Bacteroidetes and
      Actinobacteria], while the archaeal population was dominated by methanogenic
      Euryarchaeota and Crenarchaeota. In contrast, the TC streamer mat consisted of a
      bacterial population dominated by Aquificae, while the archaeal population also
      contained Korarchaeota as well as Crenarchaeota and methanogenic Euryarchaeota.
      These mats harboured clone sequences affiliated to unidentified lineages,
      suggesting that they are a potential source for discovering novel bacteria and
      archaea.

PMID- 22622648
TI  - High level expression and characterization of a thermostable lysophospholipase
      from Thermococcus kodakarensis KOD1.
AB  - Phospholipases can catalyze the hydrolysis of one or more ester and
      phosphodiester bonds and have a considerable interest in the food, oil leather
      and pharmaceutical industries. In this report, a lysophospholipase gene from the
      hyperthermophilic archaeon Thermococcus kodakarensis KOD1 (LysoPL-tk) was cloned.
      The gene of 783 bp encodes a 260-amino acid protein with a molecular mass of 29
      kDa. LysoPL-tk has a consensus motif (GxSxG) and a catalytic triad (S, D, H) of
      esterases in the deduced amino acid sequence. LysoPL-tk was expressed in
      Escherichia coli and purified to homogeneity. The enzyme can degrade substrates
      with both short and long acyl chain lengths. The apparent K (m) value for p
      nitrophenyl butyrate was 607.1 MUM with V (max) values of 95.5 U/mg. The enzyme
      was active at a broad range of pH (5-8) and temperatures (70-95  degrees C) with
      the optimum pH and temperature being 8.0 and 85  degrees C, respectively. The
      high yield, broad substrate range along with its thermo-stability indicates that
      LysoPL-tk is a potential enzyme in industrial application.

PMID- 22622649
TI  - Levosimendan versus milrinone in neonates and infants after corrective open-heart
      surgery: a pilot study.
AB  - OBJECTIVE: Low cardiac output syndrome commonly complicates the postoperative
      course after open-heart surgery in children. To prevent low cardiac output
      syndrome, prophylactic administration of milrinone after cardiopulmonary bypass
      is commonly used in small children. The aim of this study was to compare the
      effect of prophylactically administered levosimendan and milrinone on cardiac
      index in neonates and infants after corrective open-heart surgery. DESIGN:
      Prospective, single-center, double-blind, randomized pilot study. SETTING:
      Tertiary care center, postoperative pediatric cardiac intensive care unit.
      PATIENTS: After written informed consent, 40 infants undergoing corrective open
      heart surgery were included. INTERVENTIONS: At weaning from cardiopulmonary
      bypass, either a 24-hr infusion of 0.1 MUg/kg/min levosimendan or of 0.5
      MUg/kg/min milrinone were administered. Cardiac output was evaluated at 2, 6, 9,
      12, 18, 24, and 48 hrs after cardiopulmonary bypass using a transesophageal
      Doppler technique (Cardio-QP, Deltex Medical, Chichester, UK). Cardiac index was
      calculated from cardiac output and the patients' respective body surface area.
      RESULTS: Intention-to-treat data of 39 patients (19 in the levosimendan and 20 in
      the milrinone group) were analyzed using analysis of variance for repeated
      measurements for statistics. Analysis of variance revealed for both, cardiac
      index and cardiac output, similar results with no significant differences of the
      factors group and time. A significant interaction for cardiac output (p = .005)
      and cardiac index (p = .007) was found, which indicates different time courses of
      cardiac index in the two groups. Both drugs were well tolerated; no death or
      serious adverse event occurred. CONCLUSIONS: In our small study, postoperative
      cardiac index over time was similar in patients with prophylactically
      administered levosimendan and patients with prophylactically given milrinone. We
      observed an increase in cardiac output and cardiac index over time in the
      levosimendan group, whereas cardiac output and cardiac index remained stable in
      the milrinone group. This pilot study has primarily served to obtain experience
      using the new drug levosimendan in neonates and infants and to initiate further
      multicenter trials in pediatric patients.

PMID- 22622650
TI  - Reversal of dependent lung collapse predicts response to lung recruitment in
      children with early acute lung injury.
AB  - OBJECTIVE: To describe the resolution of regional atelectasis and the development
      of regional lung overdistension during a lung-recruitment protocol in children
      with acute lung injury. DESIGN: Prospective interventional trial. SETTING:
      Pediatric intensive care unit. PATIENTS: Ten children with early (<72 hrs) acute
      lung injury. INTERVENTIONS: Sustained inflation maneuver (positive airway
      pressure of 40 cm H2O for 40 secs), followed by a stepwise recruitment maneuver
      (escalating plateau pressures by 5 cm H2O every 15 mins) until physiologic lung
      recruitment, defined by PaO2 + PaCO2 >=400 mm Hg, was achieved. Regional lung
      volumes and mechanics were measured using electrical impedance tomography.
      MEASUREMENTS AND MAIN RESULTS: Patients that responded to the stepwise lung
      recruitment maneuver had atelectasis in 54% of the dependent lung regions, while
      nonresponders had atelectasis in 10% of the dependent lung regions (p = .032). In
      the pressure step preceding physiologic lung recruitment, a significant reversal
      of atelectasis occurred in 17% of the dependent lung regions (p = .016). Stepwise
      recruitment overdistended 8% of the dependent lung regions in responders, but 58%
      of the same regions in nonresponders (p < .001). Lung compliance in dependent
      lung regions increased in responders, while compliance in nonresponders did not
      improve. In contrast to the stepwise recruitment maneuver, the sustained
      inflation did not produce significant changes in atelectasis or oxygenation:
      atelectasis was only reversed in 12% of the lung (p = .122), and there was only a
      modest improvement in oxygenation (27 +/- 14 mm Hg, p = .088). CONCLUSIONS:
      Reversal of atelectasis in the most dependent lung region preceded improvements
      in gas exchange during a stepwise lung-recruitment strategy. Lung recruitment of
      dependent lung areas was accompanied by considerable overdistension of
      nondependent lung regions. Larger amounts of atelectasis in dependent lung areas
      were associated with a positive response to a stepwise lung-recruitment maneuver.

PMID- 22622651
TI  - Placement of peripherally inserted central catheters in children guided by
      ultrasound: a prospective randomized, and controlled trial.
AB  - OBJECTIVE: To compare the use of vascular Doppler ultrasound with vein
      visualization and palpation for positioning peripherally inserted central
      catheters in children and to determine the influence of these methods on the
      success of the first puncture attempt, catheter positioning, and time required
      for the accomplishment. DESIGN: A prospective randomized, controlled trial was
      conducted in a university hospital after ethical approval and was carried out
      among children (from birth to 18 yrs). SETTING: Sao Paulo Hospital, Sao Paulo,
      Brazil. PATIENTS: The sample comprises 42 peripherally inserted central catheters
      insertions allocated randomly into two groups: 1) an ultrasound group with 21
      peripherally inserted central catheters guided by ultrasound; and 2) a control
      group with 21 catheters, in which the peripherally inserted central catheters
      were inserted using vein visualization and palpation. INTERVENTIONS: The
      procedure was performed by two trained nurses using a standard protocol for
      peripherally inserted central catheter insertion and ultrasound use. Ultrasound
      group equipment was ILook25 (Sonosite, Bothell, WA) with a 25-mm, 10- to 15-MHz
      linear array transducer that reaches a 4-cm depth. MEASUREMENTS AND MAIN RESULTS:
      Success in the first puncture attempt was higher (p = .003) in the ultrasound
      group (90.5%) than in the control group (47.6%). The catheter positioning success
      rate was 85.7% in the ultrasound group and 52.4% in the control group (p = .019).
      The median time spent on the procedure for the ultrasound group was 20 mins,
      whereas it was 50 mins for the control group (p = .001). CONCLUSION: The use of
      ultrasound increased the successful positioning of peripherally inserted central
      catheters in comparison with the venous anatomic landmark visualization and
      palpation technique and further optimized the time spent on the procedure.

PMID- 22622652
TI  - Mineral metabolism:  confusion to clarity.

PMID- 22622653
TI  - MicroRNAs and fibrosis.
AB  - PURPOSE OF REVIEW: MicroRNAs (miRNAs) are short noncoding RNAs that inhibit gene
      expression in plants and animals. miRNAs have emerged as key players in virtually
      all aspects of mammalian biology. Aberrant miRNA expression is observed in
      numerous human diseases such as diabetes, hypercholesterolemia, cancer, and
      tissue fibrosis. Therefore, approaches to correct miRNA expression represent the
      novel therapeutic strategies for these diseases. RECENT FINDINGS: miRNAs are
      essential for kidney development and homeostasis. Aberrant miRNA expression is
      observed in the mouse models of kidney fibrosis. Three TGF-beta-regulated miRNA
      families, miR-21, miR-200, and miR-29 have been shown to modulate renal fibrosis.
      miR-21, through a feed-forward loop, amplifies TGF-beta signaling and promotes
      fibrosis. Conversely, miR-200 and miR-29 reduce fibrosis by inhibiting epithelial
      to-mesenchymal transition and preventing the deposition of extracellular matrix,
      respectively. Inhibition of miR-21 expression or augmenting miR-29 expression
      prevents kidney fibrosis in mice. SUMMARY: Aberrant miRNA expression perturbs
      signaling pathways that lead to progression of kidney fibrosis. Thus, miRNAs
      represent novel biomarkers and therapeutic targets in the treatment of kidney
      fibrosis.

PMID- 22622654
TI  - Lanthanide ion-doped GdPO4 nanorods with dual-modal bio-optical and magnetic
      resonance imaging properties.
AB  - Here, dual-modal bioprobes for combined optical and magnetic resonance (MR)
      imaging are reported. Gadolinium orthophosphate (GdPO(4)) nanorods co-doped with
      light-emitting lanthanide ions have been successfully prepared through a
      hydrothermal method. An efficient downconversion luminescence from Ce/Tb or Eu
      doped GdPO(4) nanorods and upconversion luminescence from Yb/Er co-doped GdPO(4)
      nanorods are observed, respectively, which offers the optical modality for the
      nanoprobes. Notably, we first report the upconversion phenomenon based on the
      GdPO(4) matrix under 980 nm near infrared irradiation. The possibility of using
      these nanoprobes with downconversion and upconversion luminescent emissions for
      optical cell imaging is also demonstrated. Furthermore, these Gd(3+)-containing
      nanophosphors show good positive signal-enhancement ability when performed under
      a 4.7 T MR imaging scanner, indicating they have potential as T(1) MR imaging
      contrast agents. Thus, nanoprobes based on GdPO(4) nanophosphors are shown to
      provide the dual modality of optical and MR imaging.

PMID- 22622655
TI  - Methods of adjusted comparison of medians.
AB  - Consider the problem of making an adjusted comparison of the medians of two
      populations on an interval type outcome variable. A common method of doing this
      is through the use of a linear model requiring the residuals to be normally
      distributed. We describe here two methods based on a linear model after Box-Cox
      transformation of the outcome variable. The methods require a reference
      population, which could be either of the populations under study or their
      aggregate. We compare the new procedures with the comparison of normal means
      procedure and other procedures proposed for this problem by simulation. It is
      found that the procedure based on comparison of the predicted values obtained
      from the observed covariates of the reference population has higher power for
      testing and smaller mean square error of estimation than the other methods, while
      maintaining reasonable control of the type I error rate. We illustrate the
      methods by analyzing the duration of the second stage of labor for women in two
      large observation studies (Collaborative Perinatal Project and Consortium on Safe
      Labor) separated by 50 years. We recommend the method based on comparison of the
      predicted values of the transformed outcomes, with careful attention to how close
      the resulting residual distribution is to normal.

PMID- 22622657
TI  - A slipped multi-decker zirconium complex with an eta7:eta2-bridging
      cycloheptatrienyl ligand.
AB  - The complex [(eta(7)-C(7)H(7))Zr{N(SiMe(3))(2)}(thf)] (2) loses THF upon
      sublimation to afford a chain polymer consisting of [(eta(7)
      C(7)H(7))Zr{N(SiMe(3))(2)}] (3) units; they are connected by cycloheptatrienyl
      ligands in an unprecedented antifacial eta(7):eta(2)-bridging mode. The basicity
      of the bis(trimethylsilyl)amido ligand can also be used to introduce other
      ligands by acid-base reactions.

PMID- 22622656
TI  - Fusion between tumor cells enhances melanoma metastatic potential.
AB  - PURPOSE: Malignant melanoma, characterized by early distant metastasis to the
      lungs and brain, is a leading cause of mortality related to skin cancer. Cell
      fusion and the subsequent aneuploidy, commonly observed in melanoma, are
      associated with poor prognosis. However, the pathological consequences of cell
      fusion in melanoma remain unknown. Therefore, the present study aims to
      investigate the pathological consequences of cell fusion in melanoma and the
      mechanism of melanoma metastasis. METHODS: Phytohemagglutinin-polyethylene glycol
      (PHA-PEG) fusion method was developed for the fusion of tumor cells. Melanoma
      cells were fused through the improved PHA-PEG fusion method and obtained by
      fluorescence-activated cell sorting. DNA content was analyzed through flow
      cytometry. Cell proliferation rate was detected by cell culture in vitro, and the
      cell number was counted daily. To detect the tumor growth rate in vivo, cells
      were injected subcutaneously and the tumor volumes were measured using a vernier
      caliper. To analyze the tumor metastatic potential, cells were injected
      intravenously, and the collected lung-metastasis samples were weighed by an
      electronic balance and the surface nodules were counted. RESULTS: We established
      an improved phytohemagglutinin-polyethylene glycol fusion method and successfully
      obtained stable melanoma tumor-tumor cell fusion hybrids. Cell size, DNA content,
      and chromosome numbers of the fusion hybrids were approximately twice those of
      the parents. The metastatic potential of the fusion hybrids was dramatically
      enhanced, in contrast to their proliferation rate. Their metastasis was specific
      to the lungs. CONCLUSIONS: We developed a highly efficient cell fusion method
      that can be applied in many fields, particularly cancer research. Our study has
      proven that tumor-tumor cell fusion hybrids in melanoma can acquire enhanced and
      specific metastatic potential. Thus, blockage of cell fusion may be a new
      strategy for melanoma metastasis therapy.

PMID- 22622659
TI  - Spitzer reassesses his 2003 study of reparative therapy of homosexuality.

PMID- 22622658
TI  - [Results of 5 to 10-year follow-up after hip resurfacing. A systematic analysis
      of the literature on long-term results].
AB  - Hip resurfacing is a common method for therapy of coxarthritis and is currently
      under discussion. The aim of this study was to analyze hip resurfacing follow-up
      studies with more than 5 years follow-up time. A total of 17 studies which
      matched the inclusion criteria were analyzed. The survival rate after 5-6 years
      was 96.3%, after 7-8 years 93.8% and after 9-10 years 90%. Young men with primary
      coxarthritis and surgery by an experienced surgeon showed the best results. The
      main causes for revision were aseptic loosening with 34.4% and fracture of the
      proximal femur with 31.9%. Dislocation as a cause for revision was rare and
      occurred in 2.8% of all cases. Hip resurfacing showed worse results than
      conventional hip arthroplasty. The risk for complications was high especially for
      women, with small prostheses and in patients with suboptimal positioning of the
      prosthesis.

PMID- 22622660
TI  - Chemical-physical changes in cell membrane microdomains of breast cancer cells
      after omega-3 PUFA incorporation.
AB  - Epidemiologic and experimental studies suggest that dietary fatty acids influence
      the development and progression of breast cancer. However, no clear data are
      present in literature that could demonstrate how n - 3 PUFA can interfere with
      breast cancer growth. It is suggested that these fatty acids might change the
      structure of cell membrane, especially of lipid rafts. During this study we
      treated MCF-7 and MDA-MB-231 cells with AA, EPA, and DHA to assess if they are
      incorporated in lipid raft phospholipids and are able to change chemical and
      physical properties of these structures. Our data demonstrate that PUFA and their
      metabolites are inserted with different yield in cell membrane microdomains and
      are able to alter fatty acid composition without decreasing the total percentage
      of saturated fatty acids that characterize these structures. In particular in MDA
      MB-231 cells, that displays the highest content of Chol and saturated fatty
      acids, we observed the lowest incorporation of DHA, probably for sterical
      reasons; nevertheless DHA was able to decrease Chol and SM content. Moreover,
      PUFA are incorporated in breast cancer lipid rafts with different specificity for
      the phospholipid moiety, in particular PUFA are incorporated in PI, PS, and PC
      phospholipids that may be relevant to the formation of PUFA metabolites
      (prostaglandins, prostacyclins, leukotrienes, resolvines, and protectines) of
      phospholipids deriving second messengers and signal transduction activation. The
      bio-physical changes after n - 3 PUFA incubation have also been highlighted by
      atomic force microscopy. In particular, for both cell lines the DHA treatment
      produced a decrease of the lipid rafts in the order of about 20-30 %. It is worth
      noticing that after DHA incorporation lipid rafts exhibit two different height
      ranges. In fact, some lipid rafts have a higher height of 6-6.5 nm. In conclusion
      n - 3 PUFA are able to modify lipid raft biochemical and biophysical features
      leading to decrease of breast cancer cell proliferation probably through
      different mechanisms related to acyl chain length and unsaturation. While EPA may
      contribute to cell apoptosis mainly through decrease of AA concentration in lipid
      raft phospholipids, DHA may change the biophysical properties of lipid rafts
      decreasing the content of cholesterol and probably the distribution of key
      proteins.

PMID- 22622661
TI  - Mitochondrial autophagy and lipofuscin accumulation in aging odontoblasts.
AB  - Aging of long-lived post-mitotic cells is characterized as a progressive and
      irreversible reduction of functional activity. In such cells, mitochondria are
      organelles critical for bioenergetic supply, whose turnover is mediated by an
      autophagic-lysosomal pathway. In human teeth, odontoblasts are post-mitotic cells
      responsible for sensory function and dentin preservation. Here, human
      odontoblasts were processed for immunohistochemistry with antibodies against
      mitochondrial (MTCO2) and lysosomal (LAMP2) markers, and comparatively analyzed
      in two age groups (young-adult and adult) with light and electron microscopy.
      Selective engulfment of mitochondrial profiles into autophagic vacuoles is common
      in young-adult odontoblasts, suggesting a microautophagic pathway. With age, the
      odontoblast layer is reduced in width, and mitochondrial elements converge around
      large clusters of autofluorescent lipofuscin deposits. Age-related changes in
      odontoblasts are observed as a long-term process in which the progressive
      accumulation of intralysosomal debris limits the autophagic turnover of
      mitochondrial components, causing an eventual decline in physiological cell
      functions, which leads to increased vulnerability under stress conditions.

PMID- 22622662
TI  - Muenke syndrome mutation, FgfR3P244R, causes TMJ defects.
AB  - Muenke syndrome is characterized by various craniofacial deformities and is
      caused by an autosomal-dominant activating mutation in fibroblast growth factor
      receptor 3 (FGFR3(P250R) ). Here, using mice carrying a corresponding mutation
      (FgfR3(P244R) ), we determined whether the mutation affects temporomandibular
      joint (TMJ) development and growth. In situ hybridization showed that FgfR3 was
      expressed in condylar chondroprogenitors and maturing chondrocytes that also
      expressed the Indian hedgehog (Ihh) receptor and transcriptional target Patched
      1(Ptch1). In FgfR3(P244R) mutants, the condyles displayed reduced levels of Ihh
      expression, H4C-positive proliferating chondroprogenitors, and collagen type II-
      and type X-expressing chondrocytes. Primary bone spongiosa formation was also
      disturbed and was accompanied by increased osteoclastic activity and reduced
      trabecular bone formation. Treatment of wild-type condylar explants with
      recombinant FGF2/FGF9 decreased Ptch1 and PTHrP expression in
      superficial/polymorphic layers and proliferation in chondroprogenitors. We also
      observed early degenerative changes of condylar articular cartilage, abnormal
      development of the articular eminence/glenoid fossa in the TMJ, and fusion of the
      articular disc. Analysis of our data indicates that the activating FgfR3(P244R)
      mutation disturbs TMJ developmental processes, likely by reducing hedgehog
      signaling and endochondral ossification. We suggest that a balance between FGF
      and hedgehog signaling pathways is critical for the integrity of TMJ development
      and for the maintenance of cellular organization.

PMID- 22622663
TI  - Coronectomy vs. total removal for third molar extraction: a systematic review.
AB  - The objective of this systematic review was to compare the outcomes between
      coronectomy and total removal for third molar extractions with high risk of nerve
      injury and to help practitioners make prudent decisions on whether and how third
      molars should be removed. PubMed, Embase, Web of Science, CENTRAL, and SIGLE were
      searched from January 1990 to October 2011 for randomized or non-randomized
      controlled trials. Four studies met our inclusion criteria. The pooled risk ratio
      (coronectomy vs. total removal) was 0.11 (95% CI = 0.03-0.36), 1.03 (95% CI =
      0.54-1.98), 0.55 (95% CI = 0.28-1.05), and 1.14 (95% CI = 0.57-2.30) for inferior
      alveolar nerve injury, post-operative infection, dry socket, and pain at 1 wk
      after surgery, respectively. A relatively high rate of failed coronectomy in one
      study (38.3%, compared with 2.3%-9.4% in others) may be attributed to a higher
      proportion of narrowing roots and vertical impactions. Although root migration
      rate was high (13.2%-85.29%), the migration distances were short (3.06 +/- 1.67
      mm), and the directions were away from the nerves. Moreover, the rates of re
      operation and root exposure were low. Therefore, coronectomy appears superior to
      total removal for reducing inferior alveolar nerve damage and could be used in
      clinical practice for third molar extractions with high risk of nerve injury.

PMID- 22622664
TI  - Systematic review and meta-analysis of outcomes after intraoperative pancreatic
      duct stent placement during pancreaticoduodenectomy.
AB  - BACKGROUND: Postoperative pancreatic leakage after pancreaticoduodenectomy is
      often serious. Although some studies have suggested that stenting the anastomosis
      can reduce the incidence of this complication, the value of stenting in the
      setting of pancreaticoduodenectomy remains unclear. METHODS: Studies comparing
      outcomes of stent versus no stent, and internal versus external stent placement
      for pancreaticoduodenectomy were eligible for inclusion. Pooled odds ratios (ORs)
      with 95 per cent confidence intervals were calculated using fixed- or random
      effects models. RESULTS: From a search of the literature published between
      January 1973 and September 2011, five randomized clinical trials (RCTs) and 11
      non-randomized observational clinical studies (OCS) involving 1726 patients were
      selected for inclusion in this review. Meta-analysis of RCTs revealed that
      placing a stent in the pancreatic duct did not reduce the incidence of
      postoperative pancreatic fistula. External stents had no advantage over internal
      stents in terms of clinical outcome. Subgroup analyses revealed that use of an
      external stent significantly reduced the incidence of pancreatic fistula (RCTs:
      OR 0.42, 0.24 to 0.76, P = 0.004; OCS: OR 0.43, 0.27 to 0.68, P < 0.001), delayed
      gastric emptying (RCTs: OR 0.41, 0.19 to 0.87, P = 0.02) and postoperative
      morbidity (RCTs: OR 0.55, 0.34 to 0.89, P = 0.02) compared with no stent.
      CONCLUSION: Pancreatic duct stenting did not reduce the incidence of pancreatic
      fistula and other complications in pancreaticoduodenectomy compared with no
      stenting. Although no difference was found between external and internal stents
      in terms of efficacy, external stents seemed to reduce the incidence of
      pancreatic fistula compared with control.

PMID- 22622665
TI  - Chiral metal-organic frameworks with tunable open channels as single-site
      asymmetric cyclopropanation catalysts.
AB  - A pair of interpenetrated and non-interpenetrated chiral metal-organic frameworks
      with the same catalytic sites but different open channel sizes catalysed
      asymmetric cyclopropanation of substituted terminal alkenes with excellent
      diastereoselectivities (up to 9.6) and enantioselectivities (up to >99%).

PMID- 22622666
TI  - Magnetically guided irrigated gold-tip catheter ablation of persistent atrial
      fibrillation--techniques, procedural parameters and outcome.
AB  - PURPOSE: Magnetically guided irrigated ablation has been introduced for atrial
      fibrillation (AF) ablation. However, data on ablation of persistent AF is scarce,
      and first-generation platinum-iridium catheters were burdened by char formation
      at the catheter tip. Furthermore, energy transmission of these catheters may be
      suboptimal. Irrigated gold-tip catheters have been introduced to overcome these
      problems. METHODS: Antral pulmonary vein (PV) isolation (PVAI) was performed
      using a 5-mm irrigated gold-tip magnetic catheter (power setting, 48  degrees C
      maximum, 50 W, 15 s lesion duration; flow-rate, 30 mL/min). The catheter tip was
      guided by a uniform magnetic field and a motor drive. Left atrial maps were
      created using an impedance-based left atrial reconstruction and fused with a
      preprocedural CT or an intraprocedural rotational angiography-based scan.
      RESULTS: Fifty-seven patients (42 male, 61.9 +/- 8.8 years) underwent PVAI for
      symptomatic, drug-refractory persistent AF. PVAI was performed successfully in
      all patients confirmed by entrance block. Procedure time (skin-to-skin) was 214
      +/- 47 min (104-354 min). Fluoroscopy time was 31 +/- 21 min. Ablation time was
      4,153 +/- 1,350 s. No char or thrombus formation was found at the catheter tip.
      One pericardial tamponade was observed. Freedom from atrial tachyarrhythmias
      could be achieved in 57.9 % of the patients included in a follow-up of 11.6 +/-
      4.2 month. There was a trend to a better outcome in patients without previous
      attempts of AF ablation (n = 48; 60.4 % vs. 44.4 %, p = 0.47). CONCLUSIONS:
      Remote magnetic navigation for PVAI seems to be safe and feasible using an
      irrigated gold-tip catheter. Effectiveness of this novel technique can be
      confirmed by mid-term outcome.

PMID- 22622668
TI  - Controlled synthesis, growth mechanism and highly efficient solar photocatalysis
      of nitrogen-doped bismuth subcarbonate hierarchical nanosheets architectures.
AB  - The synthesis and self-assembly of hierarchical architectures from nanoscale
      building blocks with unique morphology, orientation and dimension have opened up
      new opportunities to enhance their functional performances and remain a great
      challenge. This work represents tunable synthesis of various types of 3D
      monodisperse in situ N-doped (BiO)(2)CO(3) hierarchical architectures composed of
      2D single-crystal nanosheets with dominant (001) facets by a one-pot template
      free hydrothermal method from bismuth citrate and ammonia solution. Depending on
      the concentration of ammonia solution, the morphology of N-doped (BiO)(2)CO(3),
      including dandelion-like, hydrangea-like and peony flower-like microspheres, can
      be selectively constructed due to different self-assembly patterns of nanosheets.
      It was revealed that the ammonia played dual roles in the formation of N-doped
      (BiO)(2)CO(3) architectures. One is to hydrolyze bismuth citrate, and the other
      is to behave as a nitrogen doping source. The in situ doped nitrogen substituted
      for oxygen in (BiO)(2)CO(3) and subsequently narrowed the band gap, making N
      doped (BiO)(2)CO(3) visible light active. Due to the special nanosheets
      architectures, the prepared various N-doped (BiO)(2)CO(3) materials exhibited
      especially efficient photocatalytic activity and high durability for the removal
      of NO in air under both visible and UV light irradiation. Based on the direct
      observation of the growth process with respect to phase structure, chemical
      composition and morphological structure, a novel growth mechanism is revealed,
      which involves a unique multistep pathway, including reaction-nucleation,
      aggregation, crystallization, dissolution-recrystallization, and Ostwald
      ripening. The facile synthesis approach and the proposed growth mechanism could
      provide new insights into the design and controlled synthesis of inorganic
      hierarchical materials with new or enhanced properties.

PMID- 22622667
TI  - Density functional theory study of high-pressure effect on crystalline 4,4',6,6'
      tetra(azido)hydrazo-1,3,5-triazine.
AB  - Periodic density functional theory calculations are performed to study the
      hydrostatic compression effects on the structure, electronic, and thermodynamic
      properties of the energetic polyazide 4,4',6,6'-tetra(azido)hydrazo-1,3,5
      triazine (TAHT) in the range of 0-100 GPa. At the ambient pressure, the local
      density approximation/Ceperley-Alder exchange-correlation potential parameterized
      by Perdew and Zunger relaxed crystal structure compares well with the
      experimental results. The predicted heat of sublimation is 38.68 kcal/mol, and
      the evaluated condensed phase of formation (414.04 kcal/mol) approximates to the
      experimental value. The detonation velocity and detonation pressure for the solid
      TAHT are calculated to be 7.44 km/s and 23.71 GPa, respectively. When the
      pressure is exerted less than 35 GPa, the crystal structure and geometric
      parameters change slightly. However, at 36 GPa, the molecular structure, band
      structure, and density of states change abnormally because of the azide-tetrazole
      transformation that has not been observed in gas phase or polar solvents. The
      azido group cyclizes to form a five-membered tetrazole ring that is coplanar with
      the riazine ring and contributes to a larger conjunction system. As the pressure
      augments further to 80 GPa, the hydrogen transfer is found and a new covalent
      bond H2-N9 is formed. In the studied pressure range, the band gap decreases
      generally except for some breaks due to the molecular transformation and drops to
      nearly zero at 100 GPa, which means the electronic character of the crystal
      changes toward a metallic system. An analysis of the electronic structure shows
      that an applied pressure increases the impact sensitivity of TAHT.

PMID- 22622669
TI  - Giardia lamblia and respiratory allergies: a study of children from an urban area
      with a high incidence of protozoan infections.
AB  - OBJECTIVES: There is a high incidence of intestinal parasite infection in urban
      areas in the Northeast of Brazil. Giardia lamblia infections have been associated
      with increased prevalence of cutaneous allergies and gastrointestinal disorders.
      However, little is known about the relationship between giardiasis and allergic
      diseases of the airways. The present study aimed to investigate the possible
      association between respiratory allergic diseases and infections by Giardia
      lamblia in children from urban areas. METHODS: This study recruited 110 patients
      of both sexes aged 5-15 years. Patients were administered a questionnaire
      evaluating clinical symptoms and were given skin tests, parasite tests and serum
      tests. RESULTS: A high incidence of Giardia lamblia was observed (45%, 50/110).
      Infections by this protozoan were not associated with increased risk of
      respiratory allergy (p = 0.075), high total IgE levels (p = 0.701), positive
      specific IgE tests (p = 0.250), or positive skin tests for a range of
      environmental allergens (p = 0.239). CONCLUSION: This study demonstrated that
      symptoms of asthma, skin allergy and serum markers were not associated with
      Giardia lamblia infections in this sample of children from urban areas.

PMID- 22622670
TI  - Sequence and topological characterization of Toll-like receptor 8 gene of Indian
      riverine buffalo (Bubalus bubalis).
AB  - In this study, buffalo (Bubalus bubalis) Toll-like receptor 8 (TLR8) gene has
      been characterized by sequence analysis and detecting polymorphism. Complete ORF
      of buffalo TLR8 gene was amplified using the RNA isolated from spleen tissue,
      which was found to be 3,102 nucleotides long encoding a 1,033 amino acid protein.
      Buffalo TLR8 had 10 nucleotide changes as compared to other livestock species
      resulting in six unique amino acid changes, four of them lying within leucine
      rich repeat (LRR) domains. As compared to cattle (Bos indicus and Bos taurus),
      out of fifteen cysteine residues, fourteen were conserved and Cys at position 521
      was replaced by Arg. Nine of the LRR domains had no amino acid change as compared
      to cattle, whereas LRR-C-terminus had maximum, five amino acid changes. Sequence
      characterization of 12 riverine and swamp buffaloes revealed presence of four
      polymorphic nucleotides, two of them were non-synonymous, one synonymous and one
      site in 3'UTR. PCR-RFLP genotyping of non-synonymous SNP 2758A>G (ILeu920Val) in
      Toll-interleukin-1 receptor domain of 463 swamp and riverine buffaloes showed a
      higher frequency of allele A in swamp (95 %) as compared to riverine (9.84 %)
      buffaloes.

PMID- 22622671
TI  - Cellular pleomorphism in papillary tumors of the pineal region.
AB  - Papillary tumor of the pineal region (PTPR) is a recently recognized entity. We
      present the pathologic findings of two cases of PTPR as examples, and discuss the
      presence of cellular pleomorphism in these tumors. Patient 1 is a 48-year-old man
      with a pineal region mass. The tumor had unique biphasic patterns,
      papillary/pseudopapillary areas, and increased mitotic activity. Juxtaposed areas
      had marked pleomorphism, including nuclear enlargement, smudgy chromatin, nuclear
      pseudoinclusions, and cytoplasmic vacuolation. Mitoses were absent in these
      areas. Immunohistochemical staining revealed strong S100 expression. CAM 5.2 and
      CK18 were strongly positive in a patchy fashion. MIB1 labeling indices were high
      in classic PTPR regions but very low in pleomorphic areas. Patient 2 was a 35
      year-old male with a pineal region tumor characterized by papillary architecture
      and overall cellular monotony, rare mitoses, and pleomorphism as a more isolated
      finding, with associated nuclear enlargement and crowding. S100 and CAM 5.2
      labeling were present, and MIB1 labeling index was very low throughout the tumor.
      We discuss the pathologic and phenotypic features of PTPR. Variable pleomorphism
      may be present, reflected in size variation and nuclear hyperchromasia, but was
      not accompanied by increased proliferative activity in these cases, suggesting a
      degenerative phenomenon.

PMID- 22622672
TI  - Long-term use of deferiprone significantly enhances left-ventricular ejection
      function in thalassemia major patients.
AB  - A multicenter randomized open-label long-term sequential deferiprone-deferoxamine
      (DFP-DFO) versus DFP alone trial (sequential DFP-DFO) performed in patients with
      thalassemia major (TM) was retrospectively reanalyzed to assess the variation in
      the left ventricular ejection fraction (LVEF) [1].

PMID- 22622673
TI  - [Healthy aging].

PMID- 22622674
TI  - [Resources and risks in old age: the LUCAS-I marker set for a classification of
      elderly people as fit, pre-frail and frail. First results on validity from the
      Longitudinal Urban Cohort Ageing Study (LUCAS), Hamburg].
AB  - BACKGROUND: There is a need for a simple self-administered instrument to assess
      frailty in community-dwelling seniors. METHODS: We present a new marker set to
      assess the functional state of seniors. Contrary to current literature, we focus
      not only on risks, but also include resources. The questions relate to facts
      (ways to do things), rather than on subjective information (e.g. exhaustion). It
      was developed in the context of the Longitudinal Urban Cohort Ageing Study
      (LUCAS) in Hamburg, Germany. RESULTS: The classification based on these questions
      proposes operational definitions of the terms fit, pre-frail and frail and is
      predictive for need for nursing care as well as mortality. A wealth of results
      establishes the validity of the categorisation compared to other health
      questions. One of the classification questions concerns cycling. For areas where
      cycling is not suitable, we propose to replace this question with one about
      independently walking 500 m. However, the cycling question appears to indicate
      frailty earlier. CONCLUSION: The self-administered questionnaire provides a
      simple, cost-effective way to screen seniors for early signs of declining
      function in order to start preventive action.

PMID- 22622675
TI  - [Health and competence: detection and decoding using comprehensive assessments in
      the Longitudinal Urban Cohort Ageing Study (LUCAS)].
AB  - PURPOSE: The goal of this work was to characterise and distinguish persons
      without (fit), with earliest signs (pre-frail) or accelerated functional decline
      (frail) during self-referral (geriatric centre) or preventive home visits.
      METHODS: After screening independently living older people in an urban
      longitudinal cohort (n = 1,995) using a self-administered questionnaire, they
      were functionally classified as fit, pre-frail or frail. In 10% randomly selected
      samples of these cohort parts a comprehensive extended gerontological-geriatric
      assessment (EGGA) was administered. RESULTS: Fit, pre-frail and frail samples are
      significantly different regarding comorbidity, medication, mobility, fall risk,
      instrumental activities of daily living and use of social support but not
      nutrition. The best indicator to discriminate fit versus frail was exhaustion
      (mobility tiredness). CONCLUSION: Competence is essential regarding health in old
      age. Identification of resources and risks by comprehensive assessment is useful
      before planning interventions to prevent frailty or its progression.

PMID- 22622677
TI  - Physical activity and other health-related factors predict health care
      utilisation in older adults: the ActiFE Ulm study.
AB  - BACKGROUND: Health care utilisation (HCU) can be a useful outcome for estimating
      costs and patient needs. It can also be used as a surrogate parameter for healthy
      ageing. The aim of this study was to analyse the associations of formerly
      described and potentially new parameters influencing health care utilisation in
      older adults in Germany. PATIENTS AND METHODS: The ActiFE Ulm (Activity and
      Function in the Elderly in Ulm) study is a population-based study in 1,506
      community dwelling older adults aged 65-90 years in Ulm and surrounding areas in
      southwestern Germany. Between March 2009 and April 2010 a full geriatric
      assessment was performed including accelerometer-based average daily walking
      duration, comorbidity, medication, physical and psychological functioning, health
      care utilisation, sociodemographic factors etc. The association between above
      named measures and health care utilisation, represented by the number of drugs,
      the days in hospital and the number of physician contacts over one year was
      calculated in multiple regression models. Analysis was conducted among subjects
      with complete information (n = 1,059, mean age 76 years, 55% male). RESULTS: The
      average number of drugs was 4.5 and over 95% of participants visited a physician
      at least once a year while still more than 65% contacted their physician more
      than twice a year. Reduced physical activity, BMI, self-rated health and/or
      comorbidity and male sex were the best predictors of health care utilisation in
      community dwelling older adults when looking at both the number of drugs and the
      number of physician contacts over 12 months together. With regard to single
      diseases entities the best predictors of both the number of drugs and the number
      of physician contacts were asthma, chronic obstructive pulmonary disease
      (COPD)/chronic bronchitis and chronic neurological diseases (mostly Parkinson's
      disease). The number of drugs was most strongly associated with coronary heart
      disease, diabetes, and high blood pressure. CONCLUSION: Reduced walking activity,
      self-rated health and/or comorbidity and male sex are the best predictors of
      health care utilisation as measured by the number of drugs and number of
      physician contacts over 12 months. Walking activity could be regarded as the most
      promising modifiable predictor of HCU in older adults.

PMID- 22622676
TI  - [Effects of physical activity and physical training on the psychological status
      of older persons with and without cognitive impairment].
AB  - Fear of falling and depression in the elderly and among cognitively impaired
      people lead to restrictions in quality of life. Being more active is associated
      with improved mental health as documented in cross-sectional and longitudinal
      studies. This is especially true for depression. Such epidemiologic evidence is
      lacking in fear of falling. This review summarizes current evidence from
      epidemiological and randomized controlled trials (RCTs) and gives an outlook for
      future research perspectives. The majority of studies included in this review
      document a significant reduction of depression and fear of falling in older
      persons by physical training with less evidence in persons with cognitive
      impairment. With respect to intensity, duration, and amount of exercise, evidence
      based recommendations were limited by the small number of high-quality
      comparative RCTs. High-intensity strength or endurance training was the most
      effective for reducing depression, while participation in Tai-Chi or
      multifactorial training programs was most effective to reduce fear of falling.

PMID- 22622678
TI  - [Consensus for the identification of geriatric patients in the emergency care
      setting in Germany].
AB  - For the treatment of geriatric inpatients, the efficacy of a multimodal geriatric
      intervention based on findings of a comprehensive geriatric assessment has well
      been established. Therefore, the focus of elderly inpatient care switched to the
      identification of geriatric patients who have unintended or unscheduled contact
      to an accident and emergency department. In Germany, a uniform standard on how to
      correctly identify geriatric patients in such settings has yet to be
      established.Three medical societies, the Federal Association of Geriatrics
      ("Bundesverband Geriatrie", BVG), the German Society for Gerontology and
      Geriatrics ("Deutsche Gesellschaft fur Gerontologie und Geriatrie", DGGG) and the
      German Geriatrics Society ("Deutsche Gesellschaft fur Geriatrie", DGG) have
      reached a consensus on tools and instruments for the identification of geriatric
      patients in the emergency care setting. Basis of the consensus were the existing
      scientific evidence and further considerations, especially the applicability of
      international findings in Germany and feasibility.Three recommendations are made:
      (1) The use of prognostic indices is not recommended, as prognostic indices
      appear to be inappropriate to disclose the complex needs of geriatric patients.
      (2) Comprehensive geriatric assessment is established and effective, but too
      complex for use in the emergency setting. It is recommended for cases in which
      information from screening instruments or other sources does not allow a clear
      decision. (3) Among screening instruments, the Identification of Seniors At Risk
      (ISAR) screening tool seems to be well established and suitable for screening
      purposes in Germany. A German adaption is recommended as well as the
      implementation in settings where no other tools or geriatric expertise are
      available.

PMID- 22622685
TI  - Fractal gold modified electrode for ultrasensitive thrombin detection.
AB  - We report a label-free and ultrasensitive aptasensor based on a fractal gold
      modified (FracAu) electrode for thrombin detection with a femtomolar detection
      limit. The FracAu electrode was prepared by electrodeposition of hydrogen
      tetrachloroaurate (HAuCl(4)) onto a bare indium tin oxide (ITO) electrode
      surface. After this process the electrode was characterized by SEM. A thiol
      modified aptamer against thrombin was immobilized on the FracAu electrode through
      a self-assembling process. Upon thrombin binding, the interfacial electron
      transfer of the FracAu electrode was perturbed by the formation of an aptamer
      thrombin complex. The concentration of thrombin in the sample solution was
      determined by measuring the change in the oxidation peak current of hydroxymethyl
      ferrocene (C(11)H(12)FeO) with differential pulse voltammetry (DPV). The current
      response (reduced peak current) had a linear relationship with the logarithm of
      thrombin concentrations in the range of 10(-15) to 10(-10) M with a detection
      limit of 5.7 fM. Furthermore, the as-prepared FracAu electrode exhibited high
      selectivity. The application of FracAu electrodes may be extended to prepare
      other types of biosensors, such as immunosensors, enzyme biosensors and DNA
      biosensors. These results show that FracAu electrodes have great promise for
      clinical diagnosis of disease-related biomarkers.

PMID- 22622679
TI  - [Guideline-based diagnosis of dementia syndrome].
AB  - This review presents criteria for diagnosing the "syndrome of dementia" based on
      the S3 guidelines of the AWMF ("Arbeitsgemeinschaft der Wissenschaftlichen
      Medizinischen Fachgesellschaften") in Germany. They represent the best standards
      of evidence-based international knowledge, in light of the National Institute for
      Health and Clinical Excellent (NICE), the Scottish Intercollegiate Guidelines
      Network (SIGN), etc. Diagnosing dementia as early as possible is essential. All
      the current guidelines specify a two-step procedure: the first step entails
      performing a comprehensive diagnosis of the syndrome, while the second step
      involves diagnosing the precise etiology. The following article focuses on the
      first step: diagnosis of the syndrome.

PMID- 22622686
TI  - Congenital coronary arteriopathy and myocardial infarctions occur with tricuspid
      atresia.
AB  - Sinusoids and coronary arterial fistulae are well described in fetuses and
      infants with single ventricles. Coronary arteriopathy is well described as a
      cause of myocardial infarction in adults and in children with familial
      hypercholesterolemias. To the best of our knowledge, pathologic alterations in
      coronary arteries (coronary arteriopathy) have only twice before been described
      as the cause of infarction in neonates. We present the case of a newborn with
      perinatal myocardial infarctions and death in the setting of extensive coronary
      arteriopathy and tricuspid atresia. The child had a pulseless arrest immediately
      after birth. Autopsy showed multiple areas of infarction ranging in age from
      acute to >10 days old.

PMID- 22622687
TI  - Syndrome of inappropriate secretion of antidiuretic hormone associated with
      angiotensin-converting enzyme inhibitor administration.
AB  - Angiotensin-converting enzyme inhibitors (ACEI's) are an important medication in
      the treatment of congestive heart failure. However, ACEIs may cause harmful side
      effects, such as the syndrome of inappropriate secretion of antidiuretic hormone
      (SIADH), which is a rare but important side effect. We describe here a case of
      SIADH associated with ACEI administration in a 6-year-old boy with restrictive
      cardiomyopathy. After recovery from acute exacerbation of congestive heart
      failure by tolvaptan administration, an ACEI (cilazapril) was started to decrease
      the production of angiotensin II, which upregulates serum antidiuretic hormone
      secretion. The patient's heart failure symptoms worsened, including accumulation
      of right pleural effusion and ascites, after the initiation of ACEI
      administration. Cessation of ACEI administration dramatically improved his
      symptoms. Because it is difficult to distinguish SIADH associated with ACEI from
      worsening congestive heart failure, the possibility of fluid retention due to
      ACEI administration should always be considered when this agent is administered
      to patients with heart failure.

PMID- 22622688
TI  - Bat bugs (Cimex pipistrelli) and their impact on non-dwelling bats.
AB  - Bat bugs are often roost ectoparasites of bats. Previous studies have shown that
      bats shifting roosts within the growing season prevent the massive reproduction
      of these parasites. We postulated that there could be other antiparasitic
      strategies of philopatric bats roosting in non-dwelling spacious roosts.
      Unfortunately, there are no studies devoted to such a topic. For 3 years, two
      attics highly and less infested by bat bugs (Cimex pipistrelli) with breeding
      females of Myotis myotis were monitored. From April, after the arrival of the
      bats, to November, abundance of all instars and adult bugs was sampled in the
      attics by adhesive traps. We found different patterns in the bug abundances and
      dynamics in the two attics. In highly infested attic, bat bugs induced pregnant
      females to move from the infested site of the attic to the non-infested one.
      Internal temperature and relative humidity were similar in both infested and non
      infested sites. Females roosted in the infested site till time before parturition
      and then moved to the non-infested site within attic. When bats were absent in
      their old site, the abundance of nymphal instars of bugs decreased by half.
      Although adult bats can survive under high parasite loads of bat bugs,
      reproducing females prevent parasite reproduction and simultaneously reduce
      parasite load in the young by shifting inside spacious roosts.

PMID- 22622689
TI  - Acaricidal activity of eugenol on Rhipicephalus microplus (Acari: Ixodidae) and
      Dermacentor nitens (Acari: Ixodidae) larvae.
AB  - The aim of this study was to evaluate the acaricidal activity of eugenol, with
      different solubilizations and concentrations, on Rhipicephalus microplus and
      Dermacentor nitens larvae and to determine the lethal time. The study consisted
      of four experiments, and the mortality was assessed using the larval packet test
      with adaptations. The mortality observed in the first experiment was 100 % for
      all the groups treated with eugenol solubilized in different solvents. In the
      second, the hydroethanolic formulation of eugenol was used, and the mortality
      rates for R. microplus and D. nitens was 100 % starting from the concentration of
      5.0 MUl/ml. In the third experiment, the mortality was 100 % for larvae of both
      R. microplus and D. nitens after 1 h of contact. And in the fourth experiment,
      the mortality was above 90 % and statistically similar (p > 0.05) for the four
      methods the test evaluated.

PMID- 22622690
TI  - Human periosteum-derived stem cells for tissue engineering applications: the role
      of VEGF.
AB  - Mesenchymal stem cells (MSCs) are promising tools for studying the mechanisms of
      development and for the regeneration of injured tissues. Correct selection of the
      MSCs source is crucial in order to obtain a more efficient treatment and, in this
      respect Periosteum-Derived Cells (PDPCs) may represent an interesting alternative
      to bone marrow MSCs for osteochondral tissue regeneration. In the present study
      we have isolated and characterized a MSCs population from the periosteum of human
      adult donors. PDPCs were expanded under specific culture conditions that prevent
      fibroblast contamination and support the maintenance of their undifferentiated
      phenotype. We show, for the first time, that PDPCs expresses VEGF receptor (Flt1
      and KDR/Flk1) proteins and that they were similar to bone marrow Multipotent
      Adult Progenitor Cells (MAPCs). Since the latter are able to differentiate into
      endothelial cells, we tested the possible PDPCs commitment toward an endothelial
      phenotype in view of bone tissue engineering approaches that takes into account
      not only bone formation but also vascularization. PDPCs were treated with two
      different VEGF concentrations for 7 and 15 days and, alternatively, with the
      supernatant of human primary osteoblasts. Differently from MAPCs our PDPCs were
      unable to differentiate into endothelial cells after their in vitro VEGF
      treatment. On the contrary, growth factor stimulation induces PDPCs
      differentiation toward osteoblasts. We concluded that in PDPCs the presence of
      VEGF receptors is related to different cross-talk between osteogenesis and
      angiogenesis that could involve in situ PDPCs recruitment.

PMID- 22622691
TI  - Formation of soluble microbial products (SMP) by activated sludge at various
      salinities.
AB  - Soluble microbial products (SMP) present a significant component of effluent
      organic matter from biological wastewater treatment reactors, and can affect the
      membrane fouling and formation of disinfection by-products. Thus, SMP have
      attracted increasing concerns in wastewater treatment and reclamation. In this
      work, the formation of SMP by activated sludge at various NaCl concentrations is
      investigated by using fluorescence excitation-emission matrix (EEM) spectroscopy
      with parallel factor analysis (PARAFAC) and fluorescence regional integration
      (FRI). The results show that a high level of salinity decreases substrate removal
      efficiency and leads to an accumulation of SMP, especially proteins. Three
      components of SMP, one protein-like and two humic-acid-like components, are
      identified by PARAFAC, which exhibit different trends with the variation of NaCl
      concentration. FRI analysis reveals that the majority of protein fluorescence is
      attributed to tryptophan and tryptophan-like proteins, rather than tyrosine and
      tyrosine-like proteins. With an increase in NaCl concentration, the normalized
      volume percentages of tyrosine and tryptophan region increase, while those of
      humic- and fulvic-acid-like region decrease significantly. This work demonstrates
      that salinity affects the formation of SMP, and that EEM with PARAFAC in
      combination with FRI analysis is a useful tool to get insight into the formation
      of SMP by activated sludge.

PMID- 22622693
TI  - An efficient layer-by-layer self-assembly of metal-TiO2 nanoring/nanotube
      heterostructures, M/T-NRNT (M = Au, Ag, Pt), for versatile catalytic
      applications.
AB  - We have successfully developed a facile two-step anodization combined layer-by
      layer (LBL) self-assembly route for rapid fabrication of well-defined metal
      TiO(2) nanoring/nanotube combined nanostructures, i.e. M/T-NRNT (M = Au, Ag, Pt).
      These hierarchically self-assembled hybrid systems are demonstrated to exhibit
      versatile photocatalytic and catalytic reduction capabilities.

PMID- 22622696
TI  - Risk factors for spinal anesthesia in preterm infants undergoing inguinal hernia
      repair.
AB  - OBJECTIVES: To investigate the risk factors and incidence of perioperative
      adverse effects from unsupplemented spinal anesthesia in preterm infants. Times
      to resumption of oral feeding and to home discharge were also evaluated. METHODS:
      Perioperative data were collected prospectively for all preterm and former
      preterm infants who underwent inguinal hernia repair with spinal anesthesia at a
      tertiary medical center. RESULTS: The study group consisted of 144 infants with a
      median gestational age of 30 weeks, postmenstrual age of 37 weeks, birth weight
      of 1,420 g, and weight at surgery of 2,140 g. Overall, six (4.2%) infants had
      intraoperative complications, which included apnea (2/1.4%), bradycardia
      (2/1.4%), and hypoxemia (4/2.8%). Postoperative complications occurred in 15
      (10.4%) infants, mainly hypoxemia (3/2.1%), bradycardia (8/5.5%), and apnea
      (6/4.1%). Predictive factors of an unfavorable outcome (apnea, resumption of oral
      feeding > 6 h postoperatively, or discharge > 30 h postoperatively) were
      bronchopulmonary dysplasia (odds ratio [OR] = 3.2, 95% confidence interval
      [95%CI] 2.8-5.3; p = 0.01) and periventricular leukomalacia (OR = 2.8, 95%CI 2.1
      4.9; p = 0.03). CONCLUSIONS: Spinal anesthesia is safe and effective for inguinal
      hernia repair in preterm infants, with early resumption of oral feeding and short
      hospitalization. Bronchopulmonary dysplasia and periventricular leukomalacia may
      pose risks for an unfavorable outcome.

PMID- 22622695
TI  - Characterization and in vitro evaluation of bacterial cellulose membranes
      functionalized with osteogenic growth peptide for bone tissue engineering.
AB  - The aim of this study was to characterize the physicochemical properties of
      bacterial cellulose (BC) membranes functionalized with osteogenic growth peptide
      (OGP) and its C-terminal pentapeptide OGP[10-14], and to evaluate in vitro
      osteoinductive potential in early osteogenesis, besides, to evaluate cytotoxic,
      genotoxic and/or mutagenic effects. Peptide incorporation into the BC membranes
      did not change the morphology of BC nanofibers and BC crystallinity pattern. The
      characterization was complemented by Raman scattering, swelling ratio and
      mechanical tests. In vitro assays demonstrated no cytotoxic, genotoxic or
      mutagenic effects for any of the studied BC membranes. Culture with osteogenic
      cells revealed no difference in cell morphology among all the membranes tested.
      Cell viability/proliferation, total protein content, alkaline phosphatase
      activity and mineralization assays indicated that BC-OGP membranes enabled the
      highest development of the osteoblastic phenotype in vitro. In conclusion, the
      negative results of cytotoxicity, genotoxicity and mutagenicity indicated that
      all the membranes can be employed for medical supplies, mainly in bone tissue
      engineering/regeneration, due to their osteoinductive properties.

PMID- 22622694
TI  - Dynamic CO2 inhalation: a novel treatment for CSR-CSA associated with CHF.
AB  - BACKGROUND: Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) is very
      common in patients with chronic congestive heart failure (CHF). A current concept
      of the key pathophysiological mechanism leading to CSR-CSA is a fluctuation of
      PaCO2 below and above the apneic threshold. A number of therapeutic approaches
      for CSR-CSA have been proposed-all with varying success, some of which include
      various modes of positive airway pressure among other strategies. However, CO2
      oscillations seen in CSR-CSA have yet to be looked at as a specific therapeutic
      target by current treatments. DISCUSSION: Previous studies have shown that
      delivery of constant CO2 is efficacious in eliminating CSR-CSA by raising PaCO2,
      but there are serious concerns about the potential side effects, such as unwanted
      elevations in ventilation, work of breathing, and sympathetic nerve activity
      (SNA), and consequently CO2 inhalation therapy has not been recommended as a
      routine option for therapy. However, recent new studies into CO2 inhalation
      therapy have been made that may reshape its role as therapeutic. In this review,
      we will focus on the recent developments of administration of dynamic CO2 in the
      management of CSR-CSA in CHF patients.

PMID- 22622697
TI  - A block copolymer micelle template for synthesis of hollow calcium phosphate
      nanospheres with excellent biocompatibility.
AB  - We report synthesis of hollow calcium phosphate (CaP) nanospheres with high
      surface area by using block copolymer micelles as templates. The obtained CaP
      nanospheres exhibit very high biocompatibility, showing great promise for
      intracellular bio-applications in future.

PMID- 22622698
TI  - Computational study of ligand binding in lipid transfer proteins: Structures,
      interfaces, and free energies of protein-lipid complexes.
AB  - Plant nonspecific lipid transfer proteins (nsLTPs) bind a wide variety of lipids,
      which allows them to perform disparate functions. Recent reports on their
      multifunctionality in plant growth processes have posed new questions on the
      versatile binding abilities of these proteins. The lack of binding specificity
      has been customarily explained in qualitative terms on the basis of a supposed
      structural flexibility and nonspecificity of hydrophobic protein-ligand
      interactions. We present here a computational study of protein-ligand complexes
      formed between five nsLTPs and seven lipids bound in two different ways in every
      receptor protein. After optimizing geometries in molecular dynamics calculations,
      we computed Poisson-Boltzmann electrostatic potentials, solvation energies,
      properties of the protein-ligand interfaces, and estimates of binding free
      energies of the resulting complexes. Our results provide the first quantitative
      information on the ligand abilities of nsLTPs, shed new light into protein-lipid
      interactions, and reveal new features which supplement commonly held assumptions
      on their lack of binding specificity.

PMID- 22622699
TI  - Immunogenicity and safety of two tetravalent (measles, mumps, rubella, varicella)
      vaccines coadministered with hepatitis a and pneumococcal conjugate vaccines to
      children twelve to fourteen months of age.
AB  - BACKGROUND: This study compared single-dose tetravalent measles, mumps, rubella,
      varicella vaccine, Priorix-Tetra, stored refrigerated (GSK+4C) or frozen (GSK
      20C), with ProQuad (Merck-20C), when coadministered with hepatitis A vaccine
      (HAV) and 7-valent pneumococcal conjugate vaccine (PCV7). METHODS: Multicenter,
      observer-blind phase 2 study in 1783 healthy 12-14 month olds randomized to:
      GSK+4C (n = 705), GSK-20C (n = 689) or Merck-20C (n = 389), administered
      concomitantly with HAV (Havrix) and PCV7 (Prevnar). Seroresponse rates and
      antibody geometric mean concentrations/titers were determined from enzyme-linked
      immunosorbent assay and neutralization assays. Reactogenicity and safety were
      assessed. RESULTS: Seroresponse rates (day 42) were >97% for measles and rubella
      viruses and >92% for mumps virus, in all groups. Noninferiority of both GSK+4C
      and GSK-20C vaccines versus Merck-20C was demonstrated for seroresponse rates to
      measles, mumps and rubella viruses (lower 97.5% confidence interval above -5%, 
      10% and -5%, respectively). For varicella-zoster virus, seroresponse rates were
      57.1%, 69.8% and 86.7% in the GSK+4C, GSK-20C and Merck-20C groups, respectively.
      Noninferiority was not shown for either GSK vaccine (lower 97.5% confidence
      intervals <-15%). Geometric mean concentration ratios for anti-varicella-zoster
      virus demonstrated noninferiority (lower 97.5% confidence interval >= 0.5) versus
      Merck-20C for GSK-20C only. Geometric mean concentration ratios for antibodies to
      HAV and to PCV7 pneumococcal serotypes also met criteria for noninferiority for
      both GSK groups compared with Merck-20C. GSK vaccine safety was observed
      comparable to Merck-20C. Localized but not generalized measles/rubella-like rash
      and grade 3 fever was reported slightly more frequently with GSK vaccines, but
      antipyretic use was similar. The incidence of subjects experiencing at least 1
      serious adverse event was 2.0%, 2.9% and 1.8% in the GSK+4C, GSK-20C and Merck
      20C groups, respectively. CONCLUSIONS: Noninferiority of both GSK measles, mumps,
      rubella, varicella vaccines versus Merck-20C was demonstrated for responses to
      measles, mumps and rubella viruses but was not fully demonstrated for varicella
      zoster virus. The vaccines showed acceptable reactogenicity/safety when
      coadministered with HAV and PCV7.

PMID- 22622700
TI  - Regenerative cells and the architecture of beetle midgut epithelia.
AB  - The architectural ground plan of beetle and other insect midguts is represented
      by a monolayer of epithelial cells arranged in a cylindrical configuration.
      Proliferation and differentiation of regenerative cells maintain the integrity of
      this monolayer in the face of continual losses of individual cells through
      cytoplasmic budding and/or expulsion of entire epithelial cells. Peritrophic
      membranes have conventionally been considered universal features of insect
      midguts that function to protect vulnerable microvillar surfaces of the midgut
      epithelium from abrasion by ingested food; however, peritrophic membranes were
      found in only a small fraction of the adult beetle species examined in this
      study. In adult beetles, midgut epithelial cells are continually replaced by
      cells recruited from populations of mitotic regenerative cells that are
      interspersed among the differentiated epithelial monolayer. To remain contiguous
      with the other cells in the midgut monolayer, some of these proliferating
      populations have adopted evaginated configurations of cells that extend for
      varying distances from the basal surface of the monolayer. These configurations
      are referred to as regenerative crypts or pouches and consist of progenitor cells
      and stem cells. The presence, the relative densities, and the relative lengths of
      these regenerative pouches vary considerably among families of beetles. Placement
      of longitudinal muscles of the midgut relative to the proximodistal axes of these
      regenerative pouches also varies among species of beetles. The presence, the
      size, and the density of regenerative cell populations are related to 1) feeding
      habits of adult beetles, 2) presence of peritrophic membranes, and 3) expulsion
      of entire midgut epithelial cells or fragments of these epithelial cells into
      midgut lumens.

PMID- 22622701
TI  - Treatment of non-culprit lesions detected during primary PCI: long-term follow-up
      of a randomised clinical trial.
AB  - BACKGROUND: There are conflicting data regarding optimal treatment of non-culprit
      lesions detected during primary percutaneous coronary intervention (PCI) in
      patients with ST-elevation myocardial infarction (STEMI) and multi-vessel disease
      (MVD). We aimed to investigate whether ischaemia-driven early invasive treatment
      improves the long-term outcome and prevents major adverse cardiac events (MACE).
      METHODS: 121 patients with at least one non-culprit lesion were randomised in a
      2:1 manner, 80 were randomised to early fractional flow reserve (FFR)-guided PCI
      (invasive group), and 41 to medical treatment (conservative group). The primary
      endpoint was MACE at 3 years. RESULTS: Three-year follow-up was available in 119
      patients (98.3 %). There was no significant difference in all-cause mortality
      between the invasive and conservative strategy, 4 patients (3.4 %) died, all in
      the invasive group (P = 0.29). Re-infarction occurred in 14 patients (11.8 %) in
      the invasive group versus none in the conservative group (p = 0.002). Re-PCI was
      performed in 7 patients (8.9 %) in the invasive group and in 13 patients (32.5 %)
      in the conservative group (P = 0.001). There was no difference in MACE between
      these two strategies (35.4 vs 35.0 %, p = 0.96). CONCLUSIONS: In STEMI patients
      with MVD, early FFR-guided additional revascularisation of the non-culprit lesion
      did not reduce MACE at three-year follow-up compared with a more conservative
      strategy. The rate of MACE in the invasive group was predominantly driven by
      death and re-infarction, whereas in the conservative group the rate of MACE was
      only driven by repeat interventions.

PMID- 22622702
TI  - A carboxylate-based dinuclear dysprosium(III) cluster exhibiting slow magnetic
      relaxation behaviour.
AB  - Herein, we present a carboxylate-based dinuclear dysprosium compound, namely
      [Dy(2)L(6)(MeOH)(2)(H(2)O)(2)] (LH = n-butyric acid) from the reaction of
      Dy(NO(3))(3).xH(2)O with n-butyric acid and triethylamine in MeOH solvent. The
      single crystal X-ray diffraction analysis demonstrate that a total of six
      monocarboxylate ligands formed this dimeric compound by carboxylate bridging
      along with coordination from solvent molecules (water and methanol). Each Dy(III)
      ion is coordinated by nine donor atoms forming a mono-capped antiprismatic
      coordination environment. Alternating current (AC) magnetic measurements show a
      frequency dependence of the out-of-phase magnetic susceptibilities (chi'')
      indicating a slow relaxation behaviour of the magnetization.

PMID- 22622704
TI  - Quantum chemical insights into the aggregation induced emission phenomena: a
      QM/MM study for pyrazine derivatives.
AB  - There have been intensive studies on the newly discovered phenomena called
      aggregation induced emission (AIE), in contrast to the conventional aggregation
      quenching. Through combined quantum mechanics and molecular mechanics
      computations, we have investigated the aggregation effects on the excited state
      decays, both via radiative and nonradiative routes, for pyrazine derivatives 2,3
      dicyano-5,6-diphenylpyrazine (DCDPP) and 2,3-dicyanopyrazino phenanthrene (DCPP)
      in condensed phase. We show that for DCDPP there appear AIE for all the
      temperature, because the phenyl ring torsional motions in gas phase can
      efficiently dissipate the electronic excited state energy, and get hindered in
      aggregate; while for its "locked"-phenyl counterpart, DCPP, theoretical
      calculation can only give the normal aggregation quenching. These first
      principles based findings are consistent with recent experiment. The primary
      origin of the exotic AIE phenomena is due to the nonradiative decay effects. This
      is the first time that AIE is understood based on theoretical chemistry
      calculations for aggregates, which helps to resolve the present disputes over the
      mechanism.

PMID- 22622703
TI  - Emerging beneficial roles of sirtuins in heart failure.
AB  - Sirtuins are a highly conserved family of histone/protein deacetylases whose
      activity can prolong the lifespan of model organisms such as yeast, worms and
      flies. In mammalian cells, seven sirtuins (SIRT1-7) modulate distinct metabolic
      and stress-response pathways, SIRT1 and SIRT3 having been most extensively
      investigated in the cardiovascular system. SIRT1 and SIRT3 are mainly located in
      the nuclei and mitochondria, respectively. They participate in biological
      functions related to development of heart failure, including regulation of energy
      production, oxidative stress, intracellular signaling, angiogenesis, autophagy
      and cell death/survival. Emerging evidence indicates that the two sirtuins play
      protective roles in failing hearts. Here, we summarize current knowledge of
      sirtuin functions in the heart and discuss its translation into therapy for heart
      failure.

PMID- 22622707
TI  - alpha-Fe2O3 hollow structures: formation of single crystalline thin shells.
AB  - Novel alpha-Fe(2)O(3) hollow polyhedra structures with single crystalline thin
      shells were synthesized by a facile one-pot template-free hydrothermal method,
      which exhibit high efficiency on the decoloration of RhB aqueous solution in the
      presence of H(2)O(2). Based on experimental analysis, a plausible growth process
      is proposed.

PMID- 22622706
TI  - Real-time monitoring of liver damage during experimental ischaemia-reperfusion
      using a nitric oxide sensor.
AB  - BACKGROUND: Hepatic ischaemia-reperfusion (IR) injury may lead to liver damage
      during liver surgery, and intrahepatic nitric oxide (NO) levels may play a role
      in this context. The aim of this study was to demonstrate real-time changes in
      intrahepatic NO concentration during IR and to correlate potential hepatic NO
      production with liver damage using a selective NO sensor. METHODS: Wistar rats
      were exposed to 15 min of hepatic ischaemia followed by reperfusion, after which
      changes in intrahepatic NO levels were measured using an NO sensor. Additionally,
      rats were exposed to five successive periods of IR, each consisting of 15 min
      ischaemia followed by 5 or 15 min reperfusion, and hepatic damage was evaluated
      by blood tests and histological examination. Hepatic expression of Akt,
      phosphorylated Akt, endothelial nitric oxide synthase (eNOS) and phosphorylated
      eNOS was examined at different time points during and after IR by western blot
      and immunohistochemical analysis. RESULTS: During ischaemia, intrahepatic NO
      levels increased and reached a plateau at approximately 10 min. Repeated 15 min
      ischaemia-5 min reperfusion cycles reduced the maximum amount of NO produced
      during ischaemia gradually, and almost no NO production was observed during the
      fifth period of ischaemia. NO production following repeated ischaemia was
      proportional to the degree of hepatic viability. Phosphorylated eNOS was
      upregulated and correlated with the level of NO production during hepatic
      ischaemia. CONCLUSION: Intrahepatic NO levels decrease during repeated IR in
      rats. Real-time monitoring of intrahepatic NO levels is useful for the prediction
      of IR-related liver injury during experimental liver surgery.

PMID- 22622705
TI  - Auditory training in patients with unilateral cochlear implant and contralateral
      acoustic stimulation.
AB  - OBJECTIVES: It was hypothesized that auditory training would allow bimodal
      patients to combine in a better manner the low-frequency acoustic information
      provided by a hearing aid with the electric information provided by a cochlear
      implant, thus maximizing the benefit of combining acoustic (A) and electric (E)
      stimulation (EAS). DESIGN: Performance in quiet or in the presence of a
      multitalker babble at +5 dB signal to noise ratio was evaluated in seven bimodal
      patients before and after auditory training. The performance measures comprised
      identification of vowels and consonants, consonant-nucleus-consonant words,
      sentences, voice gender, and emotion. Baseline performance was evaluated in the A
      alone, E-alone, and combined EAS conditions once per week for 3 weeks. A phonetic
      contrast training protocol was used to facilitate speech perceptual learning.
      Patients trained at home 1 hour a day, 5 days a week, for 4 weeks with both their
      cochlear implant and hearing aid devices on. Performance was remeasured after the
      4 weeks of training and 1 month after training stopped. RESULTS: After training,
      there was significant improvement in vowel, consonant, and consonant-nucleus
      consonant word identification in the E and EAS conditions. The magnitude of
      improvement in the E condition was equivalent to that in the EAS condition. The
      improved performance was largely retained 1 month after training stopped.
      CONCLUSION: Auditory training, in the form administered in this study, can
      improve bimodal patients' overall speech understanding by improving E-alone
      performance.

PMID- 22622708
TI  - Highly efficient CO2 capture by tunable alkanolamine-based ionic liquids with
      multidentate cation coordination.
AB  - A series of novel alkanolamine-based ionic liquids show a highly efficient and
      excellent reversible capture of CO(2) through multidentate cation coordination
      between alkanolamine and Li(+) ion in a quasi-aza-crown ether fashion.

PMID- 22622711
TI  - An intra-cerebral drug delivery system for freely moving animals.
AB  - Microinfusions of drugs directly into the central nervous system of awake animals
      represent a widely used means of unravelling brain functions related to
      behaviour. However, current approaches generally use tethered liquid infusion
      systems and a syringe pump to deliver drugs into the brain, which often interfere
      with behaviour. We address this shortfall with a miniaturised electronically
      controlled drug delivery system (20 * 17.5 * 5 mm3) designed to be skull-mounted
      in rats. The device features a micropump connected to two 8-mm-long silicon
      microprobes with a cross section of 250 * 250 MUm2 and integrated fluid
      microchannels. Using an external electronic control unit, the device allows
      infusion of 16 metered doses (0.25 MUL each, 8 per silicon shaft). Each dosage
      requires 3.375 Ws of electrical power making the device additionally compatible
      with state-of-the-art wireless headstages. A dosage precision of 0.25 +/- 0.01
      MUL was determined in vitro before in vivo tests were carried out in awake rats.
      No passive leakage from the loaded devices into the brain could be detected using
      methylene blue dye. Finally, the device was used to investigate the effects of
      the NMDA-receptor antagonist 3-((R)-2-Carboxypiperazin-4-yl)-propyl-1-phosphonic
      acid, (R)-CPP, administered directly into the prefrontal cortex of rats during
      performance on a task to assess visual attention and impulsivity. In agreement
      with previous findings using conventional tethered infusion systems, acute (R)
      CPP administration produced a marked increase in impulsivity.

PMID- 22622710
TI  - Differentiation of bone marrow-derived cells into regenerated mesothelial cells
      in peritoneal remodeling using a peritoneal fibrosis mouse model.
AB  - Marked thickening of the peritoneum and vasculopathy in the submesothelial
      compact zone have been reported in long-term peritoneal dialysis patients. Bone
      marrow (BM)-derived cell lines are considered to be useful tools for therapy of
      various diseases. To clarify the role of BM-derived cells in the peritoneal
      fibrosis (PF) model, we analyzed several lineages of cells in the peritoneum. BM
      cells from green fluorescent protein (GFP) transgenic mice were transplanted into
      naive C57Bl/6 mice. Chlorhexidine gluconate (CG) was injected intraperitoneally
      to induce PF. Immunohistochemical analysis was performed with parietal peritoneum
      using anti-Sca-1 or -c-Kit and -GFP antibodies. Isolated BM cells were also
      transplanted into the CG-stimulated peritoneum. BM-derived cells from GFP
      transgenic mice appeared in the submesothelium from days 14 to 42. Both GFP- and
      stem cell marker-positive cells were observed in the submesothelium and on the
      surface. Isolated c-Kit-positive cells, transplanted into the peritoneal cavity,
      differentiated into mesothelial cells. In this study, we investigated whether or
      not BM-derived cells play a role in the repair of PF and immature cells have the
      potential of inducing repair of the peritoneum. The findings of this study
      suggest a new concept for therapy of PF.

PMID- 22622712
TI  - Insertion of a self-expanding metal stent for a stomal stenosis.

PMID- 22622709
TI  - Tryptophan-enriched cereal intake improves nocturnal sleep, melatonin, serotonin,
      and total antioxidant capacity levels and mood in elderly humans.
AB  - Melatonin and serotonin rhythms, which exhibit a close association with the
      endogenous circadian component of sleep, are attenuated with increasing age. This
      decrease seems to be linked to sleep alterations in the elderly. Chrononutrition
      is a field of chronobiology that establishes the principle of consuming
      foodstuffs at times of the day when they are more useful for health, improving,
      therefore, biorhythms and physical performance. Our aim was to analyze whether
      the consumption of cereals enriched with tryptophan, the precursor of both
      serotonin and melatonin, may help in the reconsolidation of the sleep/wake cycle
      and counteract depression and anxiety in 35 middle-aged/elderly (aged 55-75 year)
      volunteers in a simple blind assay. Data were collected for 3 weeks according to
      the following schedule: The control week participants consumed standard cereals
      (22.5 mg tryptophan in 30 g cereals per dose) at breakfast and dinner; for the
      treatment week, cereals enriched with a higher dose of tryptophan (60 mg
      tryptophan in 30 g cereals per dose) were eaten at both breakfast and dinner; the
      posttreatment week volunteers consumed their usual diet. Each participant wore a
      wrist actimeter that logged activity during the whole experiment. Urine was
      collected to analyze melatonin and serotonin urinary metabolites and to measure
      total antioxidant capacity. The consumption of cereals containing the higher dose
      in tryptophan increased sleep efficiency, actual sleep time, immobile time, and
      decreased total nocturnal activity, sleep fragmentation index, and sleep latency.
      Urinary 6-sulfatoxymelatonin, 5-hydroxyindoleacetic acid levels, and urinary
      total antioxidant capacity also increased respectively after tryptophan-enriched
      cereal ingestion as well as improving anxiety and depression symptoms. Cereals
      enriched with tryptophan may be useful as a chrononutrition tool for alterations
      in the sleep/wake cycle due to age.

PMID- 22622713
TI  - Cholesterolosis of the gallbladder visualized by peroral cholecystoscopy using a
      SpyGlass probe.

PMID- 22622714
TI  - Treatment of infected pancreatic pseudocysts using a novel, dedicated covered
      self-expandable metal stent (CSEMS) with an effective antimigration system.

PMID- 22622715
TI  - Use of the rendezvous technique to treat a nonhealing biliary cutaneous fistula.

PMID- 22622716
TI  - Pancreatic and lymph node metastases from maxillary osteosarcoma diagnosed by
      endoscopic ultrasound-guided fine needle aspiration.

PMID- 22622717
TI  - Endoscopic double-layered suturing: a novel technique for closure of large
      mucosal defects after endoscopic mucosal resection (EMR) or endoscopic submucosal
      dissection (ESD).

PMID- 22622718
TI  - Pyogenic granuloma of the colon.

PMID- 22622719
TI  - A rare case of small bowel intussusception.

PMID- 22622720
TI  - A case of emphysematous gastritis.

PMID- 22622721
TI  - Tumor seeding after endoscopic ultrasound-guided fine-needle aspiration of cancer
      in the body of the pancreas.

PMID- 22622722
TI  - Pretherapeutic evaluation of buried bumper syndrome by endoscopic
      ultrasonography.

PMID- 22622723
TI  - Novel technique for placement of overlapping self-expandable metal stents to
      close a massive pancreatitis-induced duodenal fistula.

PMID- 22622724
TI  - Gangliocytic paraganglioma of the duodenal papilla associated with
      esophagogastric adenocarcinoma.

PMID- 22622725
TI  - First report of a mucosa-associated lymphoid tissue (MALT) lymphoma of the
      esophagus diagnosed by endoscopic ultrasound-guided fine-needle aspiration (EUS
      FNA).

PMID- 22622726
TI  - Hyaluronic acid injection for sustained control of bleeding from a sclerotic
      ulcer base.

PMID- 22622727
TI  - Band ligation of a T1 esophageal squamous cell cancer in a patient with
      multimorbidities.

PMID- 22622728
TI  - Esophageal lesions in myeloproliferative neoplasms.

PMID- 22622729
TI  - Incidental drainage of a periappendicular abscess during colonoscopy.

PMID- 22622730
TI  - Endoloop ligation ("loop-and-let-go") of a large ileal lipoma by balloon-assisted
      enteroscopy.

PMID- 22622731
TI  - Solitary gastric metastasis from a renal cell carcinoma, presenting 23 years
      after radical nephrectomy.

PMID- 22622732
TI  - Colonic obstruction following percutaneous endoscopic gastrostomy placement.

PMID- 22622733
TI  - Acute pancreatitis due to an impacted juxtapapillary duodenal diverticulum.

PMID- 22622734
TI  - Perineurioma: an uncommon lesion in the gastrointestinal tract.

PMID- 22622735
TI  - A drinkable foreign body: acrylated resin.

PMID- 22622736
TI  - Successful drainage of recurrent pancreatic pseudocyst via a transpapillary and
      transpancreatic approach, using a conventional cystotome.

PMID- 22622737
TI  - Side-by-side dual echoendoscope and ultrathin endoscopy to facilitate EUS-ERCP
      biliary rendezvous.

PMID- 22622738
TI  - Percutaneous endoscopic gastrostomy using 10-cc syringe tubes for amyotrophic
      lateral sclerosis patients with limited mouth opening.

PMID- 22622739
TI  - Inadvertent placement of a palliative colonic stent through a malignant
      colocolonic fistula, resulting in absolute large bowel obstruction.

PMID- 22622740
TI  - Successful closure of an esophagopericardial fistula with an over-the-scope clip.

PMID- 22622741
TI  - Therapeutic endoscopic retrograde cholangiopancreatography without ultrasound or
      fluoroscopy in pregnancy.

PMID- 22622742
TI  - Bloc biopsy by tunneling method using endoscopic submucosal dissection for an
      upper gastrointestinal submucosal tumor.

PMID- 22622743
TI  - Forty years without symptoms after choledochogastrostomy.

PMID- 22622744
TI  - The "swinging" squamocolumnar junction in esophagocardiac achalasia.

PMID- 22622745
TI  - Combined biopsy forceps and scissor forceps facilitate cutting the detachable
      loop entrapped in a large pedunculated polyp.

PMID- 22622746
TI  - Major complication after Histoacryl injection for endoscopic treatment of
      bleeding peptic ulcer.

PMID- 22622747
TI  - Spleen rupture complicating upper endoscopy.

PMID- 22622748
TI  - Single-scope endoscopic ultrasound-guided rendezvous-assisted biliary stent
      insertion.

PMID- 22622749
TI  - Rescue lithotripsy to treat basket impaction.

PMID- 22622750
TI  - Endoscopic ultrasound-guided transesophageal drainage of a mediastinal pancreatic
      pseudocyst using a novel lumen-apposing metal stent.

PMID- 22622751
TI  - Xanthogranulomatous cholecystitis presenting with duodenal ulcer and
      cholecystoenteric fistula.

PMID- 22622752
TI  - Fibrin sealant for closure of mucosal penetration at the cardia during peroral
      endoscopic myotomy (POEM).

PMID- 22622753
TI  - High-definition endoscopy with i-scan enables diagnosis of characteristic mucosal
      lesions in Whipple's disease.

PMID- 22622754
TI  - Listeria monocytogenes sepsis in ulcerative colitis.

PMID- 22622755
TI  - Accidental endoscopic piercing of the tongue with an Ovesco clip.

PMID- 22622756
TI  - Epstein-Barr virus-associated early gastric cancer presenting as an elevated
      lesion.

PMID- 22622757
TI  - Small-bowel migration: a possible complication of adjustable intragastric
      balloons.

PMID- 22622758
TI  - Hypopharyngeal injury caused by overtube insertion during endoscopic submucosal
      dissection.

PMID- 22622759
TI  - A peculiar case of autoimmune pancreatitis and sclerosing cholangitis.

PMID- 22622760
TI  - Endoscopic treatment of biliary obstruction in a patient with sump syndrome.

PMID- 22622762
TI  - Metabolic syndrome in obese adolescents: a comparison of three different
      diagnostic criteria.
AB  - OBJECTIVE: To investigate the difference in the proportion of adolescents with
      metabolic syndrome diagnosed based on three different criteria, as well as the
      use of insulin resistance instead of fasting glucose. METHODS: Cross-sectional
      study with 121 obese adolescents, between 10 and 14 years old, from public
      schools of the city of Porto Alegre, Brazil, in 2011. Anthropometric, blood
      pressure, and biochemical variables were assessed. Metabolic syndrome was defined
      using three different diagnostic criteria: the International Diabetes Federation
      (IDF), Cook and de Ferranti. All of them include five components: waist
      circumference, blood pressure, high-density lipoprotein (HDL) cholesterol,
      triglycerides and fasting glucose, and there should be at least three abnormal
      results for the diagnosis of the syndrome. The Homeostasis Model Assessment -
      Insuline Resistance (HOMA-IR) was used for the characterization of insulin
      resistance. The analysis of agreement among the criteria was performed using
      Kappa statistics. RESULTS: Metabolic syndrome was diagnosed in 39.7, 51.2, and
      74.4% of adolescents, according to the IDF, Cook and de Ferranti criteria,
      respectively. There was agreement for the three diagnostic criteria in 60.3% of
      the sample. Waist circumference was the most prevalent component (81.0, 81.0, and
      96.7%), whereas high fasting glucose was the least prevalent (7.4, 1.7, and
      1.7%). The use of HOMA-IR significantly increased the proportion of positive
      diagnoses for the syndrome. CONCLUSION: The results showed significant
      differences between the three diagnostic criteria. While there is no consensus on
      the diagnostic criteria for metabolic syndrome, differences in the prevalence of
      the disease in pediatric population will be frequent.

PMID- 22622761
TI  - Integrated analysis of transcriptome and lipid profiling reveals the co
      influences of inositol-choline and Snf1 in controlling lipid biosynthesis in
      yeast.
AB  - In the yeast Saccharomyces cerevisiae many genes involved in lipid biosynthesis
      are transcriptionally controlled by inositol-choline and the protein kinase Snf1.
      Here we undertook a global study on how inositol-choline and Snf1 interact in
      controlling lipid metabolism in yeast. Using both a reference strain (CEN.PK113
      7D) and a snf1Delta strain cultured at different nutrient limitations (carbon and
      nitrogen), at a fixed specific growth rate of 0.1 h(-1), and at different
      inositol choline concentrations, we quantified the expression of genes involved
      in lipid biosynthesis and the fluxes towards the different lipid components.
      Through integrated analysis of the transcriptome, the lipid profiling and the
      fluxome, it was possible to obtain a high quality, large-scale dataset that could
      be used to identify correlations and associations between the different
      components. At the transcription level, Snf1 and inositol-choline interact either
      directly through the main phospholipid-involving transcription factors (i.e.
      Ino2, Ino4, and Opi1) or through other transcription factors e.g. Gis1, Mga2, and
      Hac1. However, there seems to be flux regulation at the enzyme levels of several
      lipid involving enzymes. The analysis showed the strength of using both
      transcriptome and lipid profiling analysis for mapping the co-influence of
      inositol-choline and Snf1 on phospholipid metabolism.

PMID- 22622763
TI  - Bacterial community composition in the water column of a lake formed by a former
      uranium open pit mine.
AB  - Mining of pyrite minerals is a major environmental issue involving both
      biological and geochemical processes. Here we present a study of an artificial
      lake of a former uranium open pit mine with the aim to connect the chemistry and
      bacterial community composition (454-pyrosequencing of 16S rRNA genes) in the
      stratified water column. A shift in the water chemistry from oxic conditions in
      the epilimnion to anoxic, alkaline, and metal and sulfide-rich conditions in the
      hypolimnion was corresponded by a strong shift in the bacterial community, with
      few shared operational taxonomic units (OTU) between the water layers. The
      epilimnetic bacterial community of the lake (~20 years old) showed similarities
      to other temperate freshwater lakes, while the hypolimnetic bacterial community
      showed similarity to extreme chemical environments. The epilimnetic bacterial
      community had dominance of Actinobacteria and Betaproteobacteria. The hypolimnion
      displayed a higher bacterial diversity and was dominated by the phototrophic
      green sulphur bacterium of the genus Chlorobium (ca. 40 % of the total
      community). Deltaproteobacteria were only represented in the hypolimnion and the
      most abundant OTUs were affiliated with ferric iron and sulfate reducers of the
      genus Geobacter and Desulfobulbus, respectively. The chemistry is clearly
      controlling, especially the hypolimnetic, bacterial community but the community
      composition also indicates that the bacteria are involved in metal cycling in the
      lake.

PMID- 22622764
TI  - Traumatic wound microbiome workshop.
AB  - On May 9-10, 2011, the Walter Reed Army Institute of Research, as the Army Center
      of Excellence for Infectious Disease, assembled over a dozen leaders in areas
      related to research into the communities of microorganisms which colonize and
      infect traumatic wounds. The objectives of the workshop were to obtain guidance
      for government researchers, to spur research community involvement in the field
      of traumatic wound research informed by a microbiome perspective, and to spark
      collaborative efforts serving the Wounded Warriors and similarly wounded
      civilians. During the discussions, it was made clear that the complexity of these
      infections will only be met by developing a new art of clinical practice that
      engages the numerous microbes and their ecology. It requires the support of
      dedicated laboratories and technologists who advance research methods such as
      community sequencing, as well as the kinds of data analysis expertise and
      facilities. These strategies already appear to be bearing fruit in the clinical
      management of chronic wounds. There are now funding announcements and programs
      supporting this area of research open to extramural collaborators.

PMID- 22622766
TI  - Bacterial communities associated with production facilities of two newly drilled
      thermogenic natural gas wells in the Barnett Shale (Texas, USA).
AB  - We monitored the bacterial communities in the gas-water separator and water
      storage tank of two newly drilled natural gas wells in the Barnett Shale in north
      central Texas, using a 16S rRNA gene pyrosequencing approach over a period of 6
      months. Overall, the communities were composed mainly of moderately halophilic
      and halotolerant members of the phyla Firmicutes and Proteobacteria (classes
      Betaeta-, Gamma-, and Epsilonproteobacteria) in both wells at all sampling times
      and locations. Many of the observed lineages were encountered in prior
      investigations of microbial communities from various fossil fluid formations and
      production facilities. In all of the samples, multiple H(2)S-producing lineages
      were encountered; belonging to the sulfate- and sulfur-reducing class
      Deltaproteobacteria, order Clostridiales, and phylum Synergistetes, as well as
      the thiosulfate-reducing order Halanaerobiales. The bacterial communities from
      the separator and tank samples bore little resemblance to the bacterial
      communities in the drilling mud and hydraulic-fracture waters that were used to
      drill these wells, suggesting the in situ development of the unique bacterial
      communities in such well components was in response to the prevalent geochemical
      conditions present. Conversely, comparison of the bacterial communities on
      temporal and spatial scales suggested the establishment of a core microbial
      community in each sampled location. The results provide the first overview of
      bacterial dynamics and colonization patterns in newly drilled, thermogenic
      natural gas wells and highlights patterns of spatial and temporal variability
      observed in bacterial communities in natural gas production facilities.

PMID- 22622767
TI  - Sharing heterogeneous data: the national database for autism research.
AB  - The National Database for Autism Research (NDAR) is a secure research data
      repository designed to promote scientific data sharing and collaboration among
      autism spectrum disorder investigators. The goal of the project is to accelerate
      scientific discovery through data sharing, data harmonization, and the reporting
      of research results. Data from over 25,000 research participants are available to
      qualified investigators through the NDAR portal. Summary information about the
      available data is available to everyone through that portal.

PMID- 22622765
TI  - High bacterial diversity in epilithic biofilms of oligotrophic mountain lakes.
AB  - Benthic microbial biofilms attached to rocks (epilithic) are major sites of
      carbon cycling and can dominate ecosystem primary production in oligotrophic
      lakes. We studied the bacterial community composition of littoral epilithic
      biofilms in five connected oligotrophic high mountain lakes located at different
      altitudes by genetic fingerprinting and clone libraries of the 16S rRNA gene.
      Different intra-lake samples were analyzed, and consistent changes in community
      structure (chlorophyll a and organic matter contents, and bacterial community
      composition) were observed along the altitudinal gradient, particularly related
      with the location of the lake above or below the treeline. Epilithic biofilm
      genetic fingerprints were both more diverse among lakes than within lakes and
      significantly different between montane (below the tree line) and alpine lakes
      (above the tree line). The genetic richness in the epilithic biofilm was much
      higher than in the plankton of the same lacustrine area studied in previous
      works, with significantly idiosyncratic phylogenetic composition (specifically
      distinct from lake plankton or mountain soils). Data suggest the coexistence of
      aerobic, anaerobic, phototrophic, and chemotrophic microorganisms in the biofilm,
      Bacteroidetes and Cyanobacteria being the most important bacterial taxa, followed
      by Alpha-, Beta-, Gamma-, and Deltaproteobacteria, Chlorobi, Planctomycetes, and
      Verrucomicrobia. The degree of novelty was especially high for epilithic
      Bacteroidetes, and up to 50 % of the sequences formed monophyletic clusters
      distantly related to any previously reported sequence. More than 35 % of the
      total sequences matched at <95 % identity to any previously reported 16S rRNA
      gene, indicating that alpine epilithic biofilms are unexplored habitats that
      contain a substantial degree of novelty within a short geographical distance.
      Further research is needed to determine whether these communities are involved in
      more biogeochemical pathways than previously thought.

PMID- 22622768
TI  - Dolphin shows and interaction programs: benefits for conservation education?
AB  - Dolphin shows and dolphin interaction programs are two types of education
      programs within zoological institutions used to educate visitors about dolphins
      and the marine environment. The current study examined the short- and long-term
      effects of these programs on visitors' conservation-related knowledge, attitude,
      and behavior. Participants of both dolphin shows and interaction programs
      demonstrated a significant short-term increase in knowledge, attitudes, and
      behavioral intentions. Three months following the experience, participants of
      both dolphin shows and interaction programs retained the knowledge learned during
      their experience and reported engaging in more conservation-related behaviors.
      Additionally, the number of dolphin shows attended in the past was a significant
      predictor of recent conservation-related behavior suggesting that repetition of
      these types of experiences may be important in inspiring people to conservation
      action. These results suggest that both dolphin shows and dolphin interaction
      programs can be an important part of a conservation education program for
      visitors of zoological facilities.

PMID- 22622769
TI  - Hydroformylation by Pt-Sn compounds from N-heterocyclic stannylenes.
AB  - [(Me(2)Si{NAr}(2))-kappa(2)N,N']Sn, reacts with PtCl(2)(L(2)) and [PtCl(MU
      Cl)(L)](2) to afford products containing Pt-Sn bonds. In the absence of
      supporting ligands L, coordination of the stannylene and rearrangement to a
      structurally unique PtSn(2)N(2)Si metallacycle occurs. The hydroformylation
      activity of a representative Pt-Sn compound is investigated.

PMID- 22622770
TI  - Kinetics for the hydrogen-abstraction of CH4 with NO2.
AB  - The detailed mechanism of the NO(2)+CH(4) reaction has been computationally
      investigated at the M06-2X/MG3S, B3LYP/6-311G(2d,d,p), and MP2/6-311+G(2df,p)
      levels. The direct dynamics calculations were preformed using canonical
      transition state theory with tunneling correction and scaled generalized normal
      mode frequencies including anharmonic torsion. The calculated results indicate
      that the NO(2)+CH(4) reaction proceeds by three distinct channels simultaneously,
      leading to the formation of trans-HONO (1a), cis-HONO (1b), and HNO(2) (1c), and
      each channel involves the formation of intermediate having lower energy than the
      final product. The anti-Hammond behavior observed in channel 1a is well analyzed.
      Proper treatment of anharmonic torsions about the C...H...O (or N) axis in the
      transition structures greatly improves the accuracy of kinetics predictions. The
      activation energy for each channel increases substantially with temperature, but
      is not strictly a linear function of temperature. Therefore, the thermal rate
      constants are fitted to the four-parameter expression recommended for this case
      over the wide temperature range 400-4000 K.

PMID- 22622771
TI  - A novel iduronate 2-sulfatase mutation in a Chinese family with
      mucopolysaccharidosis type II.
AB  - BACKGROUND: Mucopolysaccharidosis type II (MPS II; also known as Hunter syndrome)
      is an X-linked multisystem disorder resulting from the defective activity of the
      enzyme iduronate-2-sulfatase (IDS). Genetic testing is crucial in clarifying and
      diagnosing different types of MPS diseases. In this paper we report a novel IDS
      nonsense mutation resulting in MPS II in several patients from a Chinese family.
      METHODS: IDS enzyme activity, polymerase chain reaction, and DNA sequencing were
      performed to confirm the diagnosis of MPS II. RESULTS: Three patients had no
      detectable IDS activity. Two genetic tests revealed a novel IDS nonsense mutation
      (c.1030G>T, p.E344X) inherited from their mothers. The nonsense mutation
      shortened the peptide chain from 550 to 344 amino acids, which is believed to be
      a disease-causing mutation. CONCLUSIONS: MPS II is inherited in an X-linked
      manner. The risk to sibs depends on the carrier status of the mother. Genetic
      testing is necessary to identify disease-causing mutation. With this information,
      carrier testing for at-risk female relatives and prenatal testing for pregnancies
      at increased risk become possible.

PMID- 22622772
TI  - Imaging brain neuronal activity using functionalized magnetonanoparticles and
      MRI.
AB  - This study explored the use of non-radioactive 2-deoxy glucose (2DG)-labeled
      magnetonanoparticles (MNP) and magnetic resonance imaging (MRI) to detect
      functional activity during rest, peripheral stimulation, and epileptic seizures,
      in animal models. Non-radioactive 2DG was covalently attached to
      magnetonanoparticles composed of iron oxide and dextran and intravenous (tail)
      injections were performed. 2DG-MNP was injected in resting and stimulated naive
      rodents and the subsequent MRI was compared to published (14)C-2DG
      autoradiography data. Reproducibility and statistical significance was
      established in one studied model. Negative contrast enhancement (NCE) in acute
      seizures and chronic models of epilepsy were investigated. MRI NCE due to 2DG-MNP
      particles was compared to that of plain (unconjugated) MNP in one animal. NCE due
      to 2DG-MNP particles at 3 T, which is approved for human use, was also
      investigated. Histology showed presence of MNP (following intravenous injection)
      in the brain tissues of resting naive animal. 2DG-MNP intraparenchymal uptake was
      visible on MRI and histology. The locations of NCE agreed with published results
      of 2DG autoradiography in resting and stimulated animals and epileptic rats.
      Localization of epileptogenicity was confirmed by subsequent depth-electrode EEG
      (iEEG). Non-radioactive 2DG-MNP can cross the blood-brain barrier (BBB) and may
      accurately localize areas of increased activity. Although, this proof-of
      principle study involves only a limited number of animals, and much more research
      and quantification are necessary to demonstrate that 2DG-MNP, or MNPs conjugated
      with other ligands, could eventually be used to image localized cerebral function
      with MRI in humans, this MNP-MRI approach is potentially applicable to the use of
      many bioactive molecules as ligands for imaging normal and abnormal localized
      cerebral functions.

PMID- 22622773
TI  - Differential distribution of pigment-protein complexes in the Thylakoid membranes
      of Synechocystis 6803.
AB  - Thylakoids in Synechocystis 6803, though apparently uniform in appearance in
      ultrastructure, were found to consist of segments which were functionally
      dissimilar and had distinct proteomes. These thylakoid segments can be isolated
      from Synechocystis 6803 by successive ultracentrifugation of cell free extracts
      at 40,000*g (40 k segments), 90,000*g (90 k segments) and 150,000*g (150 k
      segments). Electron microscopy showed differences in their appearance. 40 k
      segments looked feathery and fluffy, whereas the 90 k and 150 k thylakoid
      membrane segments appeared tiny and less fluffy. The absorption spectra showed
      heterogeneous distribution of pigment-protein complexes in the three types of
      segments. The photochemical activities of Photosystem I (PSI) and Photosystem II
      (PSII) showed unequal distributions in 40 k, 90 k and 150 k segments which were
      substantiated with low temperature fluorescence measurements. The ratio of
      PSII/PSI fluorescence emission at 77 K (lambda(ex) = 435 nm) was highest in 150 k
      segments indicating higher PSII per unit PSI in these segments. The chlorophyll
      fluorescence lifetimes in the membranes, determined with a time-correlated single
      photon counting technique, could be resolved in three components: tau(1) (=) <40
      ps, tau(2) (=) 425-900 ps and tau(3) (=) 2.4-3.2 ns. The percentage contribution
      of the fastest component (tau(1)) decreased in the order 40 k > 90 k > 150 k
      segments whereas that of the other two components showed a reversed trend. These
      studies indicated differential distribution of pigment-protein complexes in the
      three membrane segments suggesting heterogeneity in the thylakoids of
      Synechocystis 6803.

PMID- 22622774
TI  - Clinical features and haplotype analysis of newly identified Japanese patients
      with gelsolin-related familial amyloidosis of Finnish type.
AB  - Familial amyloidosis of the Finnish type (FAF) is an autosomal dominant form of
      systematic amyloidosis characterized by lattice corneal dystrophy, cranial
      neuropathy, and cutis laxa. Although FAF has been frequently found in the Finnish
      population, FAF is a considerably rare disorder in other regions. In this study,
      we examined the clinical characteristics as well as the haplotypes of six
      Japanese patients with FAF from five families. They showed the typical clinical
      presentations of FAF, but we found a broad range of ages at onset of neurological
      symptoms. All members had the c.654G>A mutation in GSN. To evaluate the disease
      haplotypes, high-density single-nucleotide polymorphism (SNP) arrays were used
      and disease-relevant haplotypes were reconstructed. Haplotype analysis in the
      four apparently unrelated families suggested a common founder haplotype. In a
      sporadic FAF patient, however, the haplotype was dissimilar to the founder
      haplotype. The present study demonstrated that a founder mutation in most of the
      Japanese families with FAF, except for a sporadic patient in whom a de novo
      mutation event was suggested as the origin of the mutation.

PMID- 22622775
TI  - Monovalent chiral-at-copper complexes: halide-controlled diastereoselectivity.
AB  - An unusual example of diastereoselectivity has been observed in Cu(kappa(3)
      P,C,P'-1)X complexes where 1 is an asymmetric tridentate ligand containing a
      bicyclic NHC framework and X is a halide. When X is Cl(-), the S(Cu) isomer is
      formed selectively whereas when X = I(-) the R(Cu) diastereomer is preferred.

PMID- 22622776
TI  - Age does not influence the clinical outcome after high tibial osteotomy.
AB  - PURPOSE: Valgus high tibial osteotomy (HTO) is an established procedure for the
      medial gonarthrosis. In several studies, many negative influencing factors were
      evaluated. However, until now, the factor "age" was examined only insufficiently.
      The aim of our study was to evaluate the factor age in predicting the functional
      outcome after HTO, and we hypothesized that valgus HTO leads to equal results in
      the treatment of varus osteoarthritis independent of the patient's age. METHODS:
      We could generate 13 pairs of patients with a median age at operation of 57 (55
      63) years (group A) versus patients 15 years younger with a median age of 42 (39
      47) years (group B). The patients were matched according to the following
      criteria: age, gender, operation/osteosynthesis method, body mass index, same
      additional operations, and follow-up time. Evaluation of the patients was done by
      use of the Tegner and Lysholm score and visual analogue scale (VAS) as well as by
      subjective satisfaction of the patients. RESULTS: The Lysholm score showed a
      significant improvement in group A from 41 (SD +/- 12.3) to 65 (SD +/- 23.8)
      points (p = 0.01) and in group B from 33 (SD +/- 16.7) to 70 (SD +/- 31.8) points
      (p = 0.007). Moreover, the VAS decreased significantly in group A from 77 (SD +/-
      15.3) to 36 (SD +/- 21.3) points (p = 0.003) and in group B from 73 (SD +/- 22.7)
      to 41 (SD +/- 33.7) points (p = 0.02). However, there was no significant
      difference for both groups regarding the activity of the patients evaluated by
      the Tegner score (group A: preop.: 5 (1-9), follow-up: 3.5 (1-6); group B:
      preop.: 6 (3-9), follow-up: 4 (2-7)). Furthermore, there was no significant
      difference between both groups in view of the Lysholm, Tegner and VAS.
      CONCLUSION: Valgus high tibial osteotomy is an effective procedure for the
      treatment of medial gonarthrosis independent of the patient's age. As a
      consequence, the age of the patient does not have to be taken into consideration
      for the indication of high tibial osteotomy. LEVEL OF EVIDENCE: III.

PMID- 22622777
TI  - Management of knee injuries: consensus-based indications from a large community
      of orthopaedic surgeons.
AB  - PURPOSE: To describe preferences and to quantify the amount of agreement among
      orthopaedic surgeons regarding treatment options for four clinical scenarios of
      knee pathologies. METHODS: A web-based survey was developed to investigate the
      attitudes of members of an international association of surgeons specialised in
      sports traumatology and knee surgery European Society of Sports Traumatology,
      Knee Surgery and Arthroscopy. RESULTS: The response rate was 40 % (412
      questionnaires). An inter-rater agreement score (the Normalised Chi-square based
      Agreement Nomogram, NX2A) was calculated for each question. For scenario 1, 56
      year-old male, degenerative medial compartment on both the femoral and tibial
      side, the surgical approach was preferred to the conservative approach (p <
      0.001). Biological procedures were not considered appropriate, and in this
      respect, the respondents achieved a moderate degree of agreement (NX2A = 0.68).
      For scenario 2, 35-year-old male, early knee medial arthritis, the surgical
      treatment was preferred to conservative treatment (p < 0.001). The traditional
      closed-wedge tibial osteotomy was not regarded as an appropriate treatment with
      an excellent degree of agreement among surgeons (NX2A = 0.76). For scenario 3, 46
      year-old male, ACL lesion, there was an almost disagreement, as respondents
      showed no preference between a surgical and conservative approach (NX2A = 0.005).
      Among surgical treatments, an almost perfect agreement with regard to the
      appropriateness of arthroscopic single-bundle ACL reconstruction with a
      semitendinosus/gracilis graft was reached by the surgeons (NX2A = 0.8). For
      scenario 4, 69-year-old male, diffuse knee arthritis (all the compartments), an
      almost perfect agreement in favour of a total knee prosthesis was obtained for
      the management of this scenario (NX2A = 0.85). CONCLUSIONS: Web-based survey can
      help orthopaedic surgeons discuss and propose indications for clinical practice
      in the management of some of the most common joint diseases. LEVEL OF EVIDENCE:
      Cross-sectional survey, Level V.

PMID- 22622778
TI  - A historical perspective of PCL bracing.
AB  - PURPOSE: Currently there are many functional knee braces but very few designed to
      treat the posterior cruciate ligament (PCL). No PCL braces have been
      biomechanically validated to demonstrate that they provide stability with proper
      force distribution to the PCL-deficient knee. The purpose of this review was to
      evaluate the history and current state of PCL bracing and to identify areas where
      further progress is required to improve patient outcomes and treatment options.
      METHODS: A PubMed search was conducted with the terms "posterior cruciate
      ligament", "rehabilitation", "history", "knee", and "brace", and the relevant
      articles from 1967 to 2011 were analysed. A review of the current available PCL
      knee bracing options was performed. RESULTS: Little evidence exists from the
      eight relevant articles to support the biomechanical efficacy of nonoperative and
      postoperative PCL bracing protocols. Clinical outcomes reported improvements in
      reducing PCL laxity with anterior directed forces to the tibia during healing
      following PCL tears. Biomechanics research demonstrates that during knee flexion,
      the PCL experiences variable tensile forces. One knee brace has been specifically
      designed and clinically validated to improve stability in PCL-deficient knees
      during rehabilitation. While available PCL braces demonstrate beneficial patient
      outcomes, they lack evidence validating their biomechanical effectiveness.
      CONCLUSIONS: There is limited information evaluating the specific effectiveness
      of PCL knee braces. A properly designed PCL brace should apply correct anatomic
      joint forces that vary with the knee flexion angle and also provide adjustability
      to satisfy the demands of various activities. No braces are currently available
      with biomechanical evidence that satisfies these requirements. LEVEL OF EVIDENCE:
      IV.

PMID- 22622779
TI  - ACL-PCL and intercondylar notch impingement: magnetic resonance imaging of native
      and double-bundle ACL-reconstructed knees.
AB  - PURPOSE: The purpose of this study was to: (1) define the relationship between
      the ACL and PCL in normal knees; (2) determine whether ACL-PCL impingement occurs
      in native knees; and (3) determine whether there is a difference in impingement
      between double-bundle reconstructed and native knees. METHODS: Eight subjects
      were identified (age 20-50; 6 females, 2 males). All were at least 1-year status
      postanatomic double-bundle ACL reconstruction (allograft; AM = 8 mm; PL = 7 mm)
      and had no history of injury or surgery to the contralateral knee. MRIs of both
      knees were performed with the knee at 0 and 30 degrees  of flexion. The images
      were evaluated by a non-treating surgeon and two musculoskeletal radiologists.
      Coronal and sagittal angles of AM and PL bundles, Liu's PCL index and the
      distance between ACL and PCL on modified axial oblique images were recorded.
      Impingement was graded (1) no contact; (2) contact without deformation; or (3)
      contact and distortion of PCL contour. RESULTS: Seventy-five percent (6) of the
      native ACL's showed no contact with the roof of the intercondylar notch or PCL,
      compared to 25 % (2) of the double-bundle reconstructed ACLs. One double-bundle
      reconstructed ACL showed intercondylar notch roof and ACL-PCL impingement (12.5
      %). Significant differences were found between the native ACL and the double
      bundle reconstructed ACL for the coronal angle of the AM (79 degrees  vs. 72
      degrees , p = 0.002) and PL bundle (75 degrees  vs. 58 degrees , p = 0.001). No
      differences in ROM or stability were noted at any follow-up interval between
      groups based on MRI impingement grade. CONCLUSION: ACL-PCL contact occurred in 25
      % of native knees. Contact between the ACL graft and PCL occurred in 75 % of
      double-bundle reconstructed knees. ACL-PCL impingement, both contact and
      distortion of the PCL, occurred in one knee after double-bundle reconstruction.
      This study offers perspective on what can be considered normal contact between
      the ACL and PCL and how impingement after ACL reconstruction can be detected on
      MRI. LEVEL OF EVIDENCE: Cohort Study, Level III.

PMID- 22622780
TI  - Anterior fibrous bundle: a cause of residual pain and restrictive plantar flexion
      following ankle sprain.
AB  - PURPOSE: To describe anterior fibrous bundle as an intra-articular residual
      disorder following ankle sprain. METHODS: Between January 1998 and January 2009,
      we performed arthroscopy on 10 patients (7 males, 3 females; median age, 25
      years; age range, 17-43 years) who had the uncommon problem of anterior ankle
      pain accompanied by restriction of plantar flexion following an ankle sprain. Pre
      operative magnetic resonance imaging revealed osteochondral lesions (OCLs) of the
      talar dome in 3 patients, but no other findings that could explain restricted
      plantar flexion. All patients underwent arthroscopy for investigation and
      treatment of the cause of symptoms, and the 3 patients with OCL underwent
      additional arthroscopic drilling. Outcome was measured using the American
      Orthopedic Foot and Ankle Society Ankle-Hindfoot Scale (AOFAS) score, Visual
      Analogue Scale (VAS) for pain and active plantar flexion angle. RESULTS: In all
      patients, an anterior fibrous bundle was confirmed under arthroscopic
      investigation as the cause of symptoms and was resected arthroscopically. Median
      AOFAS and VAS scores improved significantly from 65 (range 61-82) and 70 (range
      50-85) pre-operatively to 95 (range 84-100) and 4 (range 0-15) at final follow
      up, respectively (p < 0.001). In addition, median active plantar flexion angle
      improved significantly from 40 degrees  (range 35-40) pre-operatively to 55
      degrees  (range 45-55), (p < 0.01). CONCLUSIONS: An anterior fibrous bundle is
      one of the intra-articular residual disorders after ankle sprain that can cause
      restriction of plantar flexion.

PMID- 22622781
TI  - Diagnosis and prognosis of acute hamstring injuries in athletes.
AB  - PURPOSE: Identification of the most relevant diagnostic and prognostic factors of
      physical examination and imaging of hamstring injuries in (elite) athletes.
      METHODS: A literature search was conducted in MEDLINE and EMBASE for articles
      between 1950 and April 2011. A survey was distributed among the members of the
      European Society of Sports Traumatology, Knee Surgery and Arthroscopy, which
      focused on physical examination, prognosis, imaging and laboratory tests of
      hamstring injuries in (elite) athletes. RESULTS: Medical history, inspection and
      palpation of the muscle bellies and imaging are most valuable at the initial
      assessment according to the literature. Experts considered medical history,
      posture and gait inspection, inspection and palpation of muscle bellies, range of
      motion tests, manual muscle testing, referred pain tests and imaging to be most
      important in the initial assessment of hamstring injuries. Magnetic resonance
      imaging (MRI) is preferred over ultrasonography and should take place within 3
      days post-trauma. Important prognostic factors are injury grade, length of the
      muscle tear on MR images, MRI-negative injuries and trauma mechanism.
      CONCLUSIONS: Posture and gait inspection, inspection and palpation of muscle
      bellies, range of motion tests, manual muscle testing and referred pain tests
      within 2 days post-trauma were identified as the most relevant diagnostic
      factors. LEVEL OF EVIDENCE: Literature review and expert opinion, Level V.

PMID- 22622782
TI  - Stress distribution inside bone after suture anchor insertion: simulation using a
      three-dimensional finite element method.
AB  - PURPOSE: To define stress distribution patterns inside a bone around suture
      anchors inserted at different angles using a three-dimensional finite element
      (FE) method. METHODS: An isotropic cube model (Young's modulus, 1,380 MPa;
      Poisson's ratio, 0.3) was designed on a computer to standardize analysis
      conditions. A virtual Twinfix anchor was inserted into the cube at two different
      angles (45 degrees  and 90 degrees ) against the top surface. A traction force
      (100 N) was applied to the anchor at six different angles (15 degrees , 30
      degrees , 45 degrees , 60 degrees , 75 degrees  and 90 degrees ) against the top
      surface. Elastic analysis was performed, and the distribution of the von Mises
      equivalent stress inside the cube was calculated. The highest value of the
      equivalent stress at each traction angle was compared between the 45 degrees  and
      90 degrees  anchor insertion settings. RESULTS: Stress concentration was most
      evident around proximal anchor threads, particularly on the traction side.
      Interestingly, stress gradually declined with an increase in traction angle only
      for the 90 degrees  insertion setting. At 15 degrees  and 90 degrees  traction
      angles, the equivalent stress was lower for the 45 degrees  insertion setting
      than for the 90 degrees  insertion setting. In contrast, the 90 degrees 
      insertion setting exhibited lower equivalent stress than the 45 degrees 
      insertion setting at 30 degrees , 45 degrees  and 60 degrees  traction angles.
      CONCLUSIONS: Insertion of an anchor at 90 degrees  might reduce the stress
      concentration around the proximal anchor threads on the traction side and provide
      lower equivalent stress in the middle range of traction angles (30 degrees -60
      degrees ) than insertion at 45 degrees . This could avoid early postoperative
      anchor failure.

PMID- 22622783
TI  - A novel feedback mechanism by Ephrin-B1/B2 in T-cell activation involves a
      concentration-dependent switch from costimulation to inhibition.
AB  - Bidirectional signals via Eph receptors/ephrins have been recognized as major
      forms of contact-dependent cell communications such as cell attraction and
      repulsion. T cells express EphBs, and their ligands, the ephrin-Bs, have been
      known as costimulatory molecules for T-cell proliferation. Recently, another
      remarkable feature of ephrin-As has emerged in the form of a concentration
      dependent transition from promotion to inhibition in axon growth. Here we
      examined whether this modification plays a role in ephrin-B costimulation in
      murine primary T cells. Low doses of ephrin-B1 and ephrin-B2 costimulated T-cell
      proliferation induced by anti-CD3, but high concentrations strongly inhibited it.
      In contrast, ephrin-B3 showed a steadily increasing stimulatory effect. This
      modulation was virtually preserved in T cells from mice simultaneously lacking
      four genes, EphB1, EphB2, EphB3, and EphB6. High concentrations of ephrin-B1/B2,
      but not ephrin-B3, inhibited the anti-CD3-induced phosphorylation of Lck and its
      downstream signals such as Erk and Akt. Additionally, high doses of any ephrin-Bs
      could phosphorylate EphB4. However, only ephrin-B1/B2 but not ephrin-B3 recruited
      SHP1, a phosphatase to suppress the phosphorylation of Lck. These data suggest
      that EphB4 signaling could engage in negative feedback to TCR signals. T-cell
      activation may be finely adjusted by the combination and concentration of ephrin
      Bs expressed in the immunological microenvironment.

PMID- 22622785
TI  - Atypical gunshot entry wound.

PMID- 22622784
TI  - In vivo toxicity and antitumor activity of mangosteen extract.
AB  - Mangosteen (Garcinia mangostana) has been widely used in the traditional medicine
      of Thailand to treat various ailments, especially diseases of the digestive
      system and infections. Many reports show antiproliferation of crude extracts and
      active constituents from mangosteen against many cancer cell lines. Therefore,
      the current study is proposed to demonstrate in vivo evidence on the antitumor
      activity of mangosteen. Crude methanolic extract (CME) from mangosteen pericarp
      including 25.19 % alpha-mangostin as an active xanthone was used in this study.
      The inhibition on tumor cell proliferation of CME was preliminarily evaluated
      against the murine colon cancer cell line NL-17 with an IC50 value of 17 and 84
      MUg/ml based on WST-1 and LDH assays, respectively. The safety dose for animal
      application was assessed by in vivo toxicity studies using female BALB/c mice.
      Acute toxicity showed an LD50 value and approximate lethal dose at 1,000 mg/kg,
      whereas the suitable dose for short-term study should be <=200 mg/kg. The
      effective dose for antitumor activity of CME was found to be between 100 and 200
      mg/kg, with a tumor size reduction of 50-70 %. Histological staining clearly
      illustrated a decrease of tumor cell density in the footpad in a dose-dependent
      manner. The median survival time and life span significantly increased in tumor
      bearing mice with CME treatment. This study suggests that CME possesses a
      powerful antitumor activity. Therefore, it is worth undertaking further
      investigation to identify active compounds and obtain a deeper understanding of
      their mechanism, in order to acquire novel effective anticancer drugs.

PMID- 22622786
TI  - Reduced pain during screening colonoscopy with an ultrathin colonoscope: a
      randomized controlled trial.
AB  - BACKGROUND AND STUDY AIMS: Screening colonoscopy for colorectal cancer (CRC) is
      recommended in several countries, but uptake rates are often low. Fear of pain
      and also time-consuming costly sedation are barriers for colonoscopy, and thus
      development of colonoscopy equipment that decreases patient discomfort is
      worthwhile. This randomized controlled trial investigated the performance of an
      ultrathin colonoscope in CRC screening. PATIENTS AND METHODS: Consecutive
      participants in a colonoscopy screening trial were randomized to examination with
      an ultrathin prototype colonoscope or a standard colonoscope. The main outcome
      measure was pain during the examination. Participants rated pain (no, slight,
      moderate, severe) using a validated questionnaire. RESULTS: From 187 enrolled
      participants (80 women [43 %]), 162 (87 %) responded to the questionnaire. The
      study groups were similar regarding baseline characteristics. Pain scores were
      significantly lower in the prototype instrument group compared with the standard
      group (78 % vs. 29 % of patients with no pain in prototype and standard groups,
      respectively; odds ratio [OR] 0.11; 95 % confidence interval [CI] 0.06 - 0.23; P
      < 0.001). Cecal intubation rate was 98 % in the prototype group and 92 % in the
      standard group (P = 0.085). Sedation was used in 2 % and 7 % in the prototype and
      standard groups respectively (P = 0.12). Adenoma detection rate was 13 % in the
      prototype group vs. 24 % in the standard group (P = 0.052). CONCLUSION: The new
      ultrathin Olympus colonoscope decreases patient pain during screening
      colonoscopy. This feature may improve uptake and patient satisfaction in
      screening colonoscopy. Further study is needed to evaluate the lower adenoma
      detection rate.

PMID- 22622787
TI  - Click and photo-unclick chemistry of aminoacrylate for visible light-triggered
      drug release.
AB  - "Click and Photo-unclick Chemistry" of aminoacrylates is proposed for a new photo
      labile linker. Adducts are built in 2 steps with good yields and cleaved rapidly
      by tissue penetrable visible light (690 nm) with a photosensitizer. Facile
      synthesis, release of mother drug, and stability and cleavage in medium are
      demonstrated.

PMID- 22622789
TI  - Transmetallation reactions of a lithium disilenide.
AB  - The first magnesium, copper and zinc disilenides were prepared via
      transmetallation reactions of a lithium disilenide and structurally
      characterised. The copper and zinc derivatives show red-shifted UV/vis
      absorptions due to admixture of metal d-orbitals to the highest occupied
      molecular orbital.

PMID- 22622788
TI  - Recommendations for ethical approaches to genotype-driven research recruitment.
AB  - Recruiting research participants based on genetic information generated about
      them in a prior study is a potentially powerful way to study the functional
      significance of human genetic variation. However, it also presents significant
      ethical challenges that, to date, have received only minimal consideration. We
      convened a multi-disciplinary workshop to discuss key issues relevant to the
      conduct and oversight of genotype-driven recruitment and to translate those
      considerations into practical policy recommendations. Workshop participants were
      invited from around the US, and included genomic researchers and study
      coordinators, research participants, clinicians, bioethics scholars, experts in
      human research protections, and government representatives. Discussion was
      directed by experienced facilitators and informed by empirical data collected in
      a national survey of IRB chairs and in-depth interviews with research
      participants in studies where genotype-driven recontact occurred. A high degree
      of consensus was attained on the resulting seven recommendations, which cover
      informed consent disclosures and choices, the process for how and by whom
      participants are recontacted, the disclosure of individual genetic research
      results, and the importance of tailoring approaches based on specific contextual
      factors. These recommendations are intended to represent a balanced approach
      protecting research participants, yet avoiding overly restrictive policies that
      hinder advancement on important scientific questions.

PMID- 22622791
TI  - Role of major revision spine surgery in recurrent adjacent segment osteoporotic
      vertebral body fracture: a case report.
AB  - STUDY DESIGN: Case report. CLINICAL QUESTION: To report the beneficial effects of
      kyphoplasty, cement augmentation and extension of posterior instrumentation in a
      patient with recurrent adjacent segment osteoporotic vertebral body fracture.
      METHODS: A 72-year-old lady underwent multiple revision spine surgeries for
      recurrent adjacent segment osteoporotic vertebral body fracture. RESULTS: The
      patient underwent four surgeries in 6 years: (1) in 2005, posterior lumbar
      interbody fusion with stabilization (L4-S1) was done; (2) in August 2010,
      implants from L4-S1 were removed and revised, transforaminal lumbar interbody
      fusion was done at L2/L3 and L3/L4 along with pedicle screw stabilization from
      T12-S1; (3) in September 2011, revision surgery was attempted, wherein a
      kyphoplasty was done at T12 and the stabilization was extended to T4; (4) again
      in October 2011, a revision surgery was attempted, wherein a kyphoplasty was done
      at T5 along with stabilization using pedicular screws in the T2 and T3 vertebrae
      and lateral mass screws in the C6 vertebra. To current date, the patient is
      stable with good sagittal and coronal balance and walking pain free without
      support. CONCLUSION: The current case demonstrates the need for posterior spinal
      reconstruction in osteoporotic vertebral collapse. Cement augmentation and
      extension of posterior instrumentation are both viable techniques that could be
      used to improve stabilization in the elderly spine.

PMID- 22622790
TI  - IgG4 production against adalimumab during long term treatment of RA patients.
AB  - PURPOSE: A substantial part of rheumatoid arthritis (RA) patients is chronically
      treated with adalimumab. Some of these patients produce antibodies against
      adalimumab, which correlate with lower serum drug levels and reduced clinical
      response. Long term exposure to antigens may result in antigen specific IgG4
      production as was demonstrated in studies on prolonged exposure to antigens such
      as different allergens, Factor VIII and IFN-beta. Here, we investigate whether
      long term treatment of RA patients with the therapeutic monoclonal antibody
      adalimumab leads to the production of specific IgG4 antibodies. METHODS: We
      developed radio immunoassays to detect total IgG or IgG4 against adalimumab and
      applied these in a cohort of 271 consecutive RA patients during 3 years of
      adalimumab treatment. RESULTS: In 32 % of the 271 patients antibodies against
      adalimumab were detectable. IgG4 antibodies were detected in 29 % of the
      patients. The proportion IgG4 of total IgG against adalimumab varies widely
      between patients, and IgG4 was found to contribute significantly to the anti drug
      antibody (ADA) response in some patients. CONCLUSION: In the immune response
      against adalimumab in adalimumab-treated RA patients a considerable part of the
      ADA is IgG4. Although IgG4 is often considered to be harmless due to its lack of
      effector function, neutralization of adalimumab by IgG4 antibodies will lead to a
      reduced clinical response.

PMID- 22622792
TI  - Anti-inflammatory treatment increases angiogenesis during early fracture healing.
AB  - OBJECTIVES: Both inflammation and angiogenesis are crucial for normal fracture
      healing. The goal of this work was to determine how anti-inflammatory treatment
      affects angiogenesis during early stages of fracture repair. METHODS: Tibia
      fractures were created in adult mice and animals were treated with indomethacin
      (2 mg/kg/day), a non-steroidal anti-inflammatory drug, or PBS once a day
      beginning from 1 day before fracture and continuing to 6 days after fracture.
      Animals were killed at 7, 14, and 28 days after injury for histomorphometric
      analysis of fracture healing. A second group of animals were killed at 3 and 7
      days after injury to measure tissue levels of VEGF and interleukin-1 beta (IL
      1beta). A third group of animals were killed at 3 and 7 days after injury for
      stereology analysis of macrophage and neutrophil infiltration and tissue
      vascularization. RESULTS: Indomethacin significantly decreased bone and cartilage
      formation at 7 days after fracture compared to controls. Indomethacin decreased
      the tissue levels of IL-1beta at 3 days after fracture but did not affect the
      recruitment of macrophages or neutrophils to injured limbs. Indomethacin-treated
      fractures had similar length density and surface density of vasculature as the
      controls at 3 days after injury. At 7 days after fracture, vasculature in
      indomethacin-treated fractures exhibited higher length density and surface
      density than that in controls. By 28 days after injury, indomethacin-treated
      fractures still exhibited defects in fracture repair. CONCLUSIONS: Anti
      inflammatory treatments using indomethacin impair bone and cartilage formation
      and increase tissue vascularization in the callus during early fracture healing.

PMID- 22622793
TI  - Stress-related femoral cortical and cancellous bone density loss after collum
      femoris preserving uncemented total hip arthroplasty: a prospective 7-year follow
      up with quantitative computed tomography.
AB  - PURPOSE: Bone loss around uncemented femoral components is suspected to precede
      implant loosening and contribute to problems in revision surgery. Short-stemmed
      cementless femoral components are designed to preserve proximal femoral bone
      stock and ultimately the longevity of the prosthesis. METHODS: With quantitative
      computed tomography-assisted osteodensitometry, we prospectively analyzed femoral
      cortical and cancellous bone density (BD) and contact area changes of an
      uncemented collum femoris preserving stem (n = 38) 10 days, 1, 3 and 7 years post
      operatively. RESULTS: Seven years post-operatively, cancellous BD (mg CaHA/mL)
      had decreased by as much as -66 % and cortical BD by up to -27 % at the
      metaphyseal portion of the femur; the decrease was progressive between the 1- and
      3-year examinations and halted thereafter. Contact area (in % out of a possible
      100 %) decreased proximally between the 1- and 3-year follow-up. CONCLUSION:
      Proximal cortical and cancellous bone density loss and decrease of contact area
      indicate that metaphyseal fixation cannot be achieved. The lack of cortical BD
      loss and increase of contact area values below the trochanter minor suggest
      diaphyseal fixation.

PMID- 22622794
TI  - Surgical treatment of osteochondritis dissecans of the talus: a systematic
      review.
AB  - PURPOSE: Osteochondritis dissecans (OCD) is an aseptic bone necrosis and
      represents pathology of high clinical relevance, which is frequently located on
      the talus. Various treatment strategies including non-surgical and surgical
      approaches have been described. An evidence-based treatment algorithm is still
      lacking. The present systematic review focuses on surgical treatment options and
      their stage-dependent outcome described for treatment of osteochondritis
      dissecans of the talus with special regard to the best available evidence.
      METHODS: For this purpose, an OVID-based systematic literature search was
      performed including the following databases; MEDLINE, MEDLINE preprints, EMBASE,
      CINAHL, Life Science Citations, British National Library of Health and Cochrane
      Central Register of Controlled trials (CENTRAL). Literature search period was
      from January 1967 up to December 2009. After applying study specific inclusion
      criteria (minimum follow-up 12 months, patient evaluation by standardized scoring
      systems, etc.), a total of 54 studies with clinical follow-up of 1,105 patients
      was included. Methodology of these studies was systematically analyzed by the
      means of the Coleman Methodology Score. Outcome and success rate was evaluated in
      dependence of surgical treatment applied and in dependence of the stage of
      disease. RESULTS: All 54 studies included were classified as evidence level IV
      representing case series. The average Coleman Methodology Score was 63 (SD +/-
      17) points. The average follow-up of the 1,105 patients was 47 months (SD +/- 17)
      with a mean age of 29 (SD +/- 5.6) years. The proportion of excellent and good
      treatment results was stage-independent in total 75 %. According to the criteria
      of the score applied for patient's evaluation in the individual study, the
      overall percentage of "good" and "excellent" clinical outcome in 869 patients was
      79 %, and according the classification of Berndt and Harty, 82 % in stage I, 86 %
      in stage II, 83 % in stage III and 76 % in stage IV. CONCLUSIONS: Although OCD of
      the talus represents a frequently observed orthopedic pathology, evidence
      concerning operative treatment of osteochondrosis dissecans of the talus is still
      elusive. With over 1,100 included patients in the present study, no strong
      recommendations based upon scientific evidence can be given.

PMID- 22622795
TI  - Which procedure is better for lumbar interbody fusion: anterior lumbar interbody
      fusion or transforaminal lumbar interbody fusion?
AB  - INTRODUCTION: Both anterior lumbar interbody fusion (ALIF) and transforaminal
      lumbar interbody fusion (TLIF) surgeries are performed to obtain a solid fusion
      to treat lumbar spondylosis. This systematic review investigated whether surgical
      complications, nonfusion rate, radiographic outcome, and clinical outcome of ALIF
      were significantly different from those of TLIF. METHOD: A computerized search of
      the electronic databases MEDLINE was conducted. Only therapeutic studies with a
      prospective or retrospective comparative design were considered for inclusion in
      the present investigation. Two reviewers independently extracted relevant data
      from each included study. Statistical comparisons were made when appropriate.
      RESULTS: Nine studies were determined to be appropriate for the systematic
      review, and all studies were retrospective comparative studies. Blood loss and
      operative time in ALIF was greater than in TLIF. There was no significant
      difference in the complication rate between ALIF and TLIF. The restoration of
      disc height, segmental lordosis, and whole lumbar lordosis in ALIF was superior
      to TLIF. However, clinical outcomes in ALIF were similar with TLIF, and there was
      no significant difference in nonfusion rate between the two techniques. Costs of
      ALIF were greater than those of TLIF. CONCLUSION: Clinical outcomes and nonfusion
      rate in ALIF were similar to TLIF. However, the restoration of disc height,
      segmental lordosis, and whole lumbar lordosis in ALIF were superior to those in
      TLIF, while blood loss, operative time, and costs in ALIF were greater than in
      TLIF.

PMID- 22622796
TI  - Wear patterns of tibiofemoral articulation in osteoarthritic knees: analysis and
      review of literature.
AB  - INTRODUCTION: Osteoarthritis is a degenerative joint disease characterized by
      progressive erosion of the articular cartilage. The sites of erosion of articular
      cartilage have been reported, but no explanation for this particular pattern has
      previously been suggested. AIMS: To analyze the gross features of lesions,
      together with their frequency of occurrence and situation, and wear relationship
      with individual body profile. MATERIALS AND METHODS: Data collected from the
      dissection of 102 cadavers at a tertiary hospital. RESULTS: Wear patterns on the
      tibial surface show that the areas involved in the majority of cases include
      middle medial and middle lateral regions of the tibial plateau. There also seemed
      to be a strong correlation between age, body mass index and the wear pattern. The
      incidence of posteromedial erosions on the tibial plateau was mainly seen in the
      ACL-deficient knee. Also, incidence of lateral meniscus tears was found to be
      higher in the ACL-deficient knees. CONCLUSION: In osteoarthritis of the knee
      joint, the middle third of both the femoral and tibial articular surfaces is most
      commonly involved in wears, followed by anteromedial and posterolateral
      compartments both for tibial and femoral surfaces. The wear patterns in the ACL
      deficient knee changes due to altered loading characteristics.

PMID- 22622797
TI  - Two-stage surgical management using posterior instrumentation, anterior
      debridement and allografting for tuberculosis of the lower lumbar spine in
      children of elementary school age: minimum 3-year follow-up of 14 patients.
AB  - PURPOSE: Various surgical methods have been described for the management of
      lumbar tuberculous spondylitis in the literature. However, there were few reports
      on the two-stage surgical treatment of lumbar tuberculosis in children of
      elementary school age. We present a retrospective clinical study of 14 patients
      with lumbar and lumbosacral tuberculous spondylitis treated by two-stage surgery
      (first stage: posterior instrumentation; second stage: anterior debridement and
      allografting). The purpose is to determine the clinical efficacy of such surgical
      treatment for lumbar tuberculosis in children. METHOD: Our series was comprised 9
      males and 5 females with an average age of 7.5 years treated with the above
      mentioned surgical procedure. All patients had lumbar and lumbosacral involvement
      with one patient having spondylitis at L2-3, three at L3-4, seven at L4-5, and
      three at L5-S1. All patients had single motion segment involvement. The Frankel
      scoring system was used to assess the neurological deficits. Frankel's grade B in
      two patients, grade C in four and grade D in eight. The following data were
      followed-up for an average period of 50.1 months (42-64 months) in these
      patients: healing of disease, deformity correction and its maintenance,
      neurologic function, and spinal bony fusion. RESULTS: The average preoperative
      local deformity angle was -13.8 degrees , correcting to 3.4 degrees 
      postoperatively and 1.5 degrees  at the final follow-up. With the exception of
      one patient who received a D at the final follow-up, all cases obtained complete
      neurological recovery. No breakage and looseness of internal fixation was found.
      Bony fusion was achieved in all cases within 6 months postoperatively. There was
      no recurrent tuberculous infection. CONCLUSION: Two-stage (posterior and
      anterior) surgery is a safe and effective procedure for the patient of elementary
      school age suffering from lumbar and lumbosacral tuberculous spondylitis,
      especially for the patients in poor general condition. The procedure has the
      advantage of minor surgical invasion, effective kyphosis correction and less
      complications.

PMID- 22622798
TI  - Insights into ozone deposition patterns from decade-long ozone flux measurements
      over a mixed temperate forest.
AB  - Long-term fluxes of ozone (O(3)) were measured over a mixed temperate forest
      using the aerodynamic gradient method. The long-term average O(3) flux (F) was 
      366 ng m(-2) s(-1) for the period 2000-2010, corresponding to an average O(3)
      concentration of 48 MUg m(-3) and a deposition velocity v(d) of 9 mm s(-1).
      Average nocturnal ozone deposition amounted to -190 ng m(-2) s(-1), which was
      about one third of the daytime flux. Also during the winter period substantial
      O(3) deposition was measured. In addition, total O(3) fluxes were found to differ
      significantly among canopy wetness categories. During the day, highest deposition
      fluxes were generally measured for a dry canopy, whereas a rain-wetted canopy
      constituted the best sink at night. Flux partitioning calculations revealed that
      the stomatal flux (F(s)) contributed 20% to the total F but the F(s)/F fraction
      was subject to seasonal and diurnal changes. The annual concentration-based index
      AOT40 (accumulated dose over a threshold of 40 ppb) and the Phytotoxic Ozone Dose
      (POD(1) or accumulated stomatal flux above a threshold of 1 nmol m(-2) s(-1))
      were related in a curvilinear way. The O(3) deposition was found to be largely
      controlled by non-stomatal sinks, whose strength was enhanced by high friction
      velocities (u(*)), optimizing the mechanical mixing of O(3) into the canopy and
      the trunk space. The long-term geometrical mean of the non-stomatal resistance
      (R(ns)) was 136 s m(-1) but lower R(ns) values were encountered during the winter
      half-year due to higher u(*). The R(ns) was also subject to a marked diurnal
      variability, with low R(ns) in the morning hours, when turbulence took off. We
      speculate that non-stomatal deposition was largely driven by scavenging of ozone
      by biogenic volatile organic compounds (BVOCs) and especially NO emitted from the
      crown or the forest floor.

PMID- 22622799
TI  - Interstitial fluid pressure as an alternate regulator of angiogenesis independent
      of hypoxia driven HIF-1alpha in solid tumors.
AB  - We previously showed that interstitial fluid pressure (IFP) may be an alternate
      regulator of angiogenesis in solid tumors. Given the accepted link between
      hypoxia-induced factor and angiogenesis this study investigated the effect of IFP
      on hypoxia-inducible factor (HIF-1alpha) and vascular endothelial growth factor
      (VEGF) in human osteosarcoma xenografts in SCID mice and in different hypoxic
      environments. Tumors were grown either at heterotopic (flank) or orthotopic
      (medullary canal of the proximal tibia) sites in the host animal. Microfluidic
      probes determined pH, O(2)-saturation, IFP, and peripheral blood flow perfusion
      continuously. We assessed tumor growth in the orthotopic site (n = 15) by softex
      radiographs weekly, 3D microCT, histological evaluation, and for molecular
      responses. An increased cytoplasmic immunohistostaining of cells for HIF-1alpha
      (p = 0.03) and VEGF-A (p = 0.004) on the outer periphery was noted compared to
      the tumor center, with VEGFR2 uniformly stained throughout. This paralleled a
      raised state of interstitial hypertension (p = 0.007) in the tumor center
      relative to the peripheral surface but was inconsistent with a state of hypoxia
      (p = 0.03) in the tumor center. In vitro culture of human osteosarcoma cell lines
      (HOS, U2OS) and a human osteoblast control at 0- and 20-mmHg of hydrostatic
      pressure revealed suppression of HIF-1alpha (p = 0.02) and VEGF-A (p = 0.02) gene
      expression when IFP was raised, while the effect on VEGFR1 was equivocal. This
      study proposes an alternative regulatory angiogenic pathway via the influence of
      IFP on cancer cell function. The identification of a mechanistic cellular link to
      the physical parameter becomes an important tool to evaluate cancer cell growth
      within solid tumors.

PMID- 22622801
TI  - Modifications of adiposity in school-age children according to nutritional
      status: a 20-year analysis.
AB  - OBJECTIVE: To analyze adiposity changes in school-age children over a 20 year
      period, according to nutritional status. METHODS: The study is part of the
      Ilhabela Longitudinal Mixed Project on Growth, Development and Physical Fitness.
      A sample of 1,095 school students of both sexes, from 7 to 10 years, met the
      following inclusion criteria: (a) at least one complete assessment in one of the
      analyzed periods; (b) to be in prepubertal stage of sexual maturation; (c) to be
      apparently healthy. The periods analyzed were 1990/1991 (initial), 2000/2001 (10
      years) and 2010/2011 (20 years). The variables analyzed were: body weight, height
      and adiposity through individual analysis of each skinfold. Children were
      classified as eutrophic, overweight and obese, according to the curves of body
      mass index for age and sex proposed by the World Health Organization. The
      statistical analysis used was one-way ANOVA, followed by Scheffe's post-hoc test,
      with p < 0.01. RESULTS: In boys, the largest increase occurred in the overweight
      group, followed by the obese and eutrophic groups. In girls, the largest
      increases occurred in the groups with overweight and eutrophic children, followed
      by the obese group. CONCLUSION: During the 20-year period analyzed, there were
      changes in adiposity, even when the nutritional status was controlled, showing
      that individuals who have similar body mass indexes may vary in proportion and
      distribution of subcutaneous adipose tissue. In both sexes, the increase was
      higher in the overweight group, and mainly in central skinfolds.

PMID- 22622800
TI  - IL-10 deficiency blocks the ability of LPS to regulate expression of tolerance
      related molecules on dendritic cells.
AB  - Interleukin-10 (IL-10) is an anti-inflammatory cytokine that plays an important
      role in regulating the local inflammatory immune response, but regulatory
      mechanisms of this cytokine have not been fully elucidated. Here, we demonstrate
      that IL-10 deficiency renders LPS treatment ineffective in regulating the
      expression of CD40, CD80, CD86, B7-H2, and B7-DC on dendritic cells (DCs) and
      blocks upregulation of IL-27. This inability to respond to LPS was found in both
      IL-10(-/-)  bone marrow derived and splenic DCs. Compared with wild-type DCs, IL
      10(-/-)  DCs expressed similar levels of TLR4 and CD14, but produced less LPS
      binding protein. The deficiency in LPS-binding protein production may explain the
      failure of IL-10(-/-)  DCs to respond normally to LPS. Moreover, lack of IL-10
      modulated the proportions of CD11c(+) CD8(+)  and CD11c(+) B220(+)  DCs, which
      play an important role in local inflammatory responses and tolerance. IL-10
      deficiency also blocked expression of galectin-1, CD205, and CD103, which are
      necessary for central and peripheral tolerance. While they did not respond to
      LPS, IL-10(-/-)  DCs produced increased levels of IL-6 and CCL4 after TNF-alpha
      treatment. Together, our results demonstrate that IL-10 deficiency affects the
      immune functions of DCs, which may contribute to the increased severity of
      autoimmune diseases seen in IL-10(-/-)  mice.

PMID- 22622802
TI  - AMPK activation by AICAR inhibits myogenic differentiation and myostatin
      expression in cattle.
AB  - AMP-activated protein kinase (AMPK) regulates metabolism in skeletal muscle, and
      myostatin (MSTN) negatively regulates skeletal muscle development and growth. In
      the present study, AMPK activation and the relationship between AMPK and MSTN
      during myogenic differentiation were investigated in cultures derived from bovine
      skeletal muscle. Myoblasts capable of forming myotubes were obtained from bovine
      skeletal muscle and treated with AICAR to activate AMPK, resulting in suppressed
      myotube formation. AICAR treatment significantly reduced the expression of MSTN
      mRNA during myogenic differentiation. Combined treatment with AICAR and MSTN
      suppressed myotube formation to a greater extent than AICAR alone. SB431542, an
      inhibitor of MSTN signaling, promoted myotube formation during myogenic
      differentiation. However, simultaneous treatment with AICAR blocked this effect
      of SB431542. Therefore, AMPK activation inhibits myogenic differentiation but may
      suppress MSTN expression to balance muscle development.

PMID- 22622803
TI  - Pattern of expression of vascular endothelial growth factor and its receptors in
      the ovine choroid plexus during long and short photoperiods.
AB  - Vascular endothelial growth factor (VEGF-A) plays an important role in
      maintaining cerebrospinal fluid (CSF) homeostasis and the function of the choroid
      plexuses (CPs). The objective of the study was to determine the expression of
      vascular endothelial growth factor (VEGF-A), tyrosine kinase receptors Flt-1 and
      KDR and KDR co-receptor neuropilin 1 (NRP-1) in ovine CPs during different
      photoperiods. CPs were collected from the lateral brain ventricles from
      ovariectomized, estradiol-treated ewes during long day (LD; 16L:8D, n = 5) and
      short day (SD; 8L:16D, n = 5) photoperiods. We analyzed mRNA expression levels of
      two VEGF-A isoforms, VEGF-A (120) and VEGF-A (164) and our results indicate that
      VEGF-A (164) was the predominant isoform. Expression levels of VEGF-A and Flt-1
      were similar during the SD and LD photoperiods. There were significant increases
      in KDR mRNA and protein expression (p < 0.05) and NRP-1 mRNA expression (p <
      0.05) during SD. These data show that expression of KDR and its co-receptor NRP-1
      are up-regulated by short photoperiod and that this effect is not dependent on
      ovarian steroids. Our results suggest that the VEGF-A-system may be involved in
      photoperiodic plasticity of CP capillaries and may therefore be responsible for
      photoperiodic changes in the CSF turnover rate in ewes.

PMID- 22622804
TI  - Micro-RNAs (miRNAs): genomic organisation, biogenesis and mode of action.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression in
      animals and in plants. In recent years, miRNAs have been shown to be important
      biological molecules for regulating various cellular functions. miRNAs function
      post-transcriptionally usually by base-pairing to the mRNA 3'-untranslated
      regions of the mRNAs and repress protein synthesis by mechanisms that are not
      fully understood. Various miRNA genes have been mapped in the genome of a number
      of organisms and the list continues to grow. Details regarding the genomic
      organisation, transcriptional regulation and post-transcriptional maturation of
      miRNAs are still emerging. In this review, information regarding the genomic
      organisation, biogenesis and regulation of expression of miRNAs is discussed.

PMID- 22622805
TI  - Force communication in multicellular tissues addressed by laser nanosurgery.
AB  - Cell contractility is a prominent mechanism driving multicellular tissue
      development and remodeling. Forces originated by the actomyosin cytoskeleton not
      only act within the cell body but can also propagate many layers away from the
      contraction source and grant tissues the ability to organize collectively and to
      achieve robust remodeling through development. Tissue tension is being thoroughly
      investigated in model organisms and increasing evidence is revealing the major
      role played by the communication, dynamics and propagation of cell-to-cell
      physical forces in multicellular remodeling. Recently, pulsed-laser-based surgery
      has fostered in vivo experimental studies to investigate intracellular and
      supracellular forces in action. The technique offers a unique method to perturb
      mechanical equilibrium in a subpopulation of cells or in a single cell, while the
      overall tissue remains intact. In particular, improved ablation precision with
      short laser pulses and the combination of this technique with biophysical models
      now allow an in-depth understanding of the role of cellular mechanics in tissue
      morphogenesis. We first characterize laser ablation modes available to perform
      intracellular, cellular, or multi-cellular ablation via the example of the model
      monolayer tissue of the amnioserosa of Drosophila by relating subnanosecond laser
      pulse energy to ablation efficiency and the probability of cavitation bubble
      formation. We then review recent laser nanosurgery experiments that have been
      performed in cultured cells and that tackle actomyosin mechanics and provide
      molecular insights into force-sensing mechanisms. We finally review studies
      showing the central role of laser ablation in revealing the nature and
      orientation of forces involved in intracellular contractility and force
      mechanosensing in tissue development, e.g., axis elongation, branching
      morphogenesis, or tissue invagination. We discuss the perspectives offered by the
      technique in force-based cell-cell communication and mechanosensing pathways.

PMID- 22622806
TI  - Catalytic activity of halohydrin dehalogenases towards spiroepoxides.
AB  - A novel activity of halohydrin dehalogenases towards spiroepoxides has been
      found. The enzyme from Arthrobacter sp. (HheA) catalysed highly regioselective
      azidolysis of spiroepoxides containing 5, 6 and 7-membered cycloalkane rings,
      while the enzyme from Agrobacterium radiobacter (HheC), besides high
      regioselectivity, also displayed moderate to high enantioselectivity (E up to
      >200) that can be applied for the kinetic resolution of chiral spiroepoxides. The
      orientations of spiroepoxides in the active site of halohydrin dehalogenases were
      studied by quantum-chemical calculations and docking simulations. Analyses of the
      complexes obtained revealed the origins of diastereoselectivity and
      enantioselectivity of the investigated biotransformations.

PMID- 22622807
TI  - Use of tamoxifen and raloxifene for breast cancer chemoprevention in 2010.
AB  - Two selective estrogen receptor modulators, tamoxifen and raloxifene, have been
      shown in randomized clinical trials to reduce the risk of developing primary
      invasive breast cancer in high-risk women. In 1998, the U.S. Food and Drug
      Administration (FDA) used these studies as a basis for approving tamoxifen for
      primary breast chemoprevention in both premenopausal and postmenopausal women at
      high risk. In 2007, the FDA approved raloxifene for primary breast cancer
      chemoprevention for postmenopausal women. Data from the year 2010 National Health
      Interview Survey were analyzed to estimate the prevalence of tamoxifen and
      raloxifene use for chemoprevention of primary breast cancers among U.S. women.
      Prevalence of use of chemopreventive agents for primary tumors was 20,598 (95 %
      CI, 518-114,864) for U.S. women aged 35-79 for tamoxifen. Prevalence was 96,890
      (95 % CI, 41,277-192,391) for U.S. women aged 50-79 for raloxifene. Use of
      tamoxifen and raloxifene for prevention of primary breast cancers continues to be
      low. In 2010, women reporting medication use for breast cancer chemoprevention
      were primarily using the more recently FDA approved drug raloxifene. Multiple
      possible explanations for the low use exist, including lack of awareness and/or
      concern about side effects among primary care physicians and patients.

PMID- 22622809
TI  - Adolescent intakes of vitamin D and calcium and incidence of proliferative benign
      breast disease.
AB  - Vitamin D and calcium have been shown to have protective effects against breast
      cancer development in animal studies. Vitamin D and calcium play important
      anticarcinogenic roles in animal studies. Exposures between menarche and first
      birth may be important in breast development and future breast cancer risk.
      However, the relations between adolescent vitamin D and calcium intake and the
      risk of proliferative benign breast disease (BBD), a marker of increased breast
      cancer risk, have not yet been evaluated. We examined these associations in the
      Nurses' Health Study II. Among the 29,480 women who completed an adolescent diet
      questionnaire in 1998, 682 proliferative BBD cases were identified and confirmed
      by centralized pathology review between 1991 and 2001. Hazard ratios (HRs) and 95
      % confidence intervals (CIs) were estimated by Cox proportional hazards
      regression and adjusted for potential confounders. A suggestive inverse
      association was observed between adolescent total vitamin D intake and
      proliferative BBD. Women in the highest quintile of vitamin D intake during
      adolescence had a 21 % lower risk (multivariate HR (95 % CI): 0.79 (0.61, 1.01),
      p-trend = 0.07) of proliferative BBD than women in the lowest quintile. Results
      were essentially the same when the analysis was restricted to prospective cases
      (n = 142) diagnosed after return of the adolescent diet questionnaire and
      independent of adult vitamin D intake. Adolescent total milk intake was
      positively associated with proliferative BBD (>=3 servings/day vs. <1 serving/day
      HR (95 % CI): 1.41 (0.91, 2.17), p-trend = 0.03), after additional adjustment for
      total vitamin D. Calcium intake during adolescence was not associated with
      proliferative BBD (p-trend = 0.91). Vitamin D intake during adolescence may be
      important in the earlier stage of breast carcinogenesis. These findings, if
      corroborated, may suggest new pathways and strategies for breast cancer
      prevention.

PMID- 22622808
TI  - Estrogen receptor beta binds Sp1 and recruits a corepressor complex to the
      estrogen receptor alpha gene promoter.
AB  - Human estrogen receptors alpha and beta are crucially involved in the regulation
      of mammary growth and development. Normal breast tissues display a relative
      higher expression of ER beta than ER alpha, which drastically changes during
      breast tumorogenesis. Thus, it is reasonable to suggest that a dysregulation of
      the two estrogen receptor subtypes may induce breast cancer development. However,
      the molecular mechanisms underlying the potential opposing roles played by the
      two estrogen receptors on tumor cell growth remain to be elucidated. In the
      present study, we have demonstrated that ER beta overexpression in breast cancer
      cells decreases cell proliferation and down-regulates ER alpha mRNA and protein
      content, along with a concomitant repression of estrogen-regulated genes.
      Transient transfection experiments, using a vector containing the human ER alpha
      promoter region, showed that elevated levels of ER beta down-regulated basal ER
      alpha promoter activity. Furthermore, site-directed mutagenesis and deletion
      analysis revealed that the proximal GC-rich motifs at -223 and -214 are critical
      for the ER beta-induced ER alpha down-regulation in breast cancer cells. This
      occurred through ER beta-Sp1 protein-protein interactions within the ER alpha
      promoter region and the recruitment of a corepressor complex containing the
      nuclear receptor corepressor NCoR, accompanied by hypoacetylation of histone H4
      and displacement of RNA-polymerase II. Silencing of NCoR gene expression by RNA
      interference reversed the down-regulatory effects of ER beta on ER alpha gene
      expression and cell proliferation. Our results provide evidence for a novel
      mechanism by which overexpression of ER beta through NCoR is able to down
      regulate ER alpha gene expression, thus blocking ER alpha's driving role on
      breast cancer cell growth.

PMID- 22622810
TI  - NSAID analgesic ketorolac used perioperatively may suppress early breast cancer
      relapse: particular relevance to triple negative subgroup.
AB  - To explain a bimodal relapse hazard among early stage breast cancer patients
      treated by mastectomy we postulated that relapses within 4 years of surgery
      resulted from something that happened at about the time of surgery to provoke
      sudden exits from dormant phases to active growth. Relapses at 10 months appeared
      to be surgery-induced angiogenesis of dormant avascular micrometastases. Another
      relapse mode with peak about 30 months corresponded to sudden growth from a
      single cell. Late relapses were not synchronized to surgery. This hypothesis
      could explain a wide variety of breast cancer observations. We have been looking
      for new data that might provide more insight concerning the various relapse
      modes. Retrospective data reported in June 2010 study of 327 consecutive patients
      compared various perioperative analgesics and anesthetics in one Belgian hospital
      and one surgeon. Patients were treated with mastectomy and conventional adjuvant
      therapy. Follow-up was average 27.3 months with range 13-44 months. Updated
      hazard as of September 2011 for this series is now presented. NSAID ketorolac, a
      common analgesic used in surgery, is associated with far superior disease-free
      survival in the first few years after surgery. The expected prominent early
      relapse events are all but absent. In the 9-18 month period, there is fivefold
      reduction in relapses. If this observation holds up to further scrutiny, it could
      mean that the simple use of this safe and effective anti-inflammatory agent at
      surgery might eliminate most early relapses. Transient systemic inflammation
      accompanying surgery could be part of the metastatic tumor seeding process and
      could have been effectively blocked by perioperative anti-inflammatory agents. In
      addition, antiangiogenic properties of NSAIDs could also play a role. Triple
      negative breast cancer may be the ideal group with which to test perioperative
      ketorolac to prevent early relapses.

PMID- 22622811
TI  - Prognostic implications of estrogen receptor pattern of both tumors in
      contralateral breast cancer.
AB  - Estrogen receptor (ER) status is important for breast cancer survival, it is
      however unclear how prognosis of contralateral breast cancer (CBC) is affected by
      ER-status of the two tumors. We conducted a large, population-based study of ER
      status of both tumors in CBC patients and its influence on prognosis. The cohort
      consisted of all women diagnosed with CBC in Stockholm, Sweden during 1976-2005,
      with information on ER-status from medical records (N = 933). Prognosis was
      modeled as incidence rates of distant metastasis via Poisson regression. The
      proportion of CBCs with both cancers of the same ER-status was significantly
      larger than expected by chance. For synchronous (simultaneous) cancers the
      prognosis was significantly affected by the combined ER-status of both tumors (p
      = 0.01). Compared to unilateral breast cancer patients the incidence rate ratio
      (IRR) for patients with double ER-positive tumors was 1.25 (95 % CI: 0.88-1.76),
      for ER-discordant tumors 2.19 (95 % CI: 1.18-4.08) and for double ER-negative
      tumors 3.95 (95 % CI: 1.77-8.81). For metachronous (non-simultaneous) cancers,
      women with double ER-positive tumors had similarly bad prognosis (IRR = 2.95; 95
      % CI: 2.39-3.64) as women with double ER-negative tumors (IRR = 2.88; 95 % CI:
      1.83-4.52). Both shorter time span between first and second cancer and endocrine
      therapy for the first cancer further worsened prognosis of women with double ER
      positive metachronous CBC. For synchronous CBC patients, ER-pattern of both
      tumors is an important prognosticator, while among metachronous CBC patients,
      double ER-positive tumors confer equally bad prognosis as double ER-negative
      cancers. Our results indicate that this might be due to endocrine therapy
      resistance.

PMID- 22622813
TI  - Preference for biological motion in domestic chicks: sex-dependent effect of
      early visual experience.
AB  - To examine the effects of early visual experience on preference for biological
      motion (BM), newly hatched chicks were exposed to a point-light animation (a
      visual stimulus composed of identical light points) depicting the following
      features of a hen: a walking hen (a BM stimulus), a rotating hen (a non-BM
      stimulus), a pendulum stimulus, a random motion stimulus and a stationary
      pattern. Chicks were then tested in a binary choice task, choosing between
      walking-hen and rotating-hen stimuli. Males exhibited a preference for BM if they
      had been trained with any animation except the stationary pattern stimulus,
      suggesting that the BM preference was not learned, but induced by motion stimuli.
      We found a significant positive correlation between the number of approaches in
      training and the preference in the test, but locomotion alone did not cause
      preference for BM. In contrast, females exhibited a particularly strong
      preference for walking-hen stimuli, but only when they had been trained with it.
      Furthermore, females (but not males) trained with random motion showed a
      preference for walking hen over walking cat (a biological motion animation
      depicting a cat), possibly suggesting that females are choosier than males.
      Chicks trained with a stationary pattern and untrained controls did not show a
      significant preference. The induction of BM preference is discussed in terms of
      possible ecological background of the sex differences.

PMID- 22622812
TI  - Isolation and characterization of Planctomycetes from the sediments of a fish
      farm wastewater treatment tank.
AB  - The increasing ecological significance of Planctomycetes and the still limited
      knowledge of this group prompted us to obtain cultured isolates from the sediment
      of a treatment water recycling tank of a marine fish farm. Presence of strains
      from this group was assessed in the sediments and water column of the tank.
      Eleven isolates were obtained from the sediment sample by exploiting
      Planctomycetes natural resistance to several antibiotics and their capacity to
      degrade organic matter. Based on morphological characteristics and resistance to
      antibiotics, Planctomycetes were identified. Their phylogenetic affiliation was
      confirmed by the sequence analysis of the 16S rRNA gene that revealed the
      presence of a group of 6 isolates closely related to Rhodopirellula baltica and a
      cluster of 5 isolates with 97.7-97.9 % of similarity to this species, which
      probably are a different species of Rhodopirellula. ERIC-PCR profiles showed a
      higher discrimination within the two groups and allowed the identification of
      nine different genotypes within the isolated strains. This work corroborates the
      association of Rhodopirellula spp. with fish farm environments.

PMID- 22622814
TI  - Omission of expected reward agitates Atlantic salmon (Salmo salar).
AB  - The evolutionary background for cognition and awareness is currently under ardent
      scrutiny. Poikilothermic vertebrates such as teleost fishes are capable of
      classical conditioning and have long-term memories, but it remains unknown to
      what degree such capabilities are associated with affective states. Here, we
      investigate whether the concept of frustration may apply to Atlantic salmon. In
      mammals, this paradigm comprises the omission of an expected reward (OER), which
      elicits behavioural and physiological coping responses (e.g. aggression and
      stress reactions). Six groups with 200 fish in each were conditioned to associate
      a flashing light (CS) with feeding. Conditioning over 22 days led to a change
      from aversion to attraction to the CS. Subsequently, 3 groups served as control,
      and 3 groups were subjected to an OER paradigm for 9 days, in which the expected
      food reward was delayed for 30 min during two out of three daily meals. Compared
      to controls, OER groups displayed higher levels of aggression and more
      heterogeneous growth rates, indicating a more pronounced social hierarchy.
      Cortisol levels did, however, not differ between treatments and both groups
      responded similarly to acute stress. These results indicate that teleost fishes,
      like mammals, respond aggressively to OER. The capacity to respond behaviourally
      to frustrating conditions thus likely reflects an adaptive response to
      environmental unpredictability, which has been conserved throughout vertebrate
      evolution.

PMID- 22622815
TI  - Manganese(III)-mediated radical cyclisations for the (Z)-selective synthesis of
      exo-alkylidene pyrrolidinones and pyrrolidines.
AB  - The cyclisation of alkynyl amido- and amino-malonates in the presence of
      manganese(III) acetate gives exo-alkylidene pyrrolidinones and pyrrolidines with
      a preference for the (Z)-alkene product isomer.

PMID- 22622816
TI  - Paramagnetic relaxation enhancement for the characterization of the
      conformational heterogeneity in two-domain proteins.
AB  - Multidomain proteins are often composed of rigid domains that can reorient in
      solution more or less freely. Calmodulin (CaM) is a two domain protein which can
      experience a large degree of conformational freedom thanks to a mobile linker
      connecting the N-terminal and C-terminal domains of the protein. The maximum
      occurrences (MOs) of the possible protein conformations have been analyzed using
      the paramagnetic relaxation enhancements (PREs) induced by a gadolinium(III) ion
      together with the paramagnetic pseudocontact shift and residual dipolar coupling
      restraints measured in the presence of terbium(III), thulium(III) or
      dysprosium(III) ions. The results suggest that the PREs provide complementary
      information useful for improving the description of the conformational
      heterogeneity of the protein. The data, acquired at 298 K and at 278 K, suggest
      that compact conformations are disfavoured by decreasing the temperature.

PMID- 22622817
TI  - Biomedical application of fuzzy association rules for identifying breast cancer
      biomarkers.
AB  - Current breast cancer research involves the study of many different prognosis
      factors: primary tumor size, lymph node status, tumor grade, tumor receptor
      status, p53, and ki67 levels, among others. High-throughput microarray
      technologies are allowing to better understand and identify prognostic factors in
      breast cancer. But the massive amounts of data derived from these technologies
      require the use of efficient computational techniques to unveil new and relevant
      biomedical knowledge. Furthermore, integrative tools are needed that effectively
      combine heterogeneous types of biomedical data, such as prognosis factors and
      expression data. The objective of this study was to integrate information from
      the main prognostic factors in breast cancer with whole-genome microarray data to
      identify potential associations among them. We propose the application of a data
      mining approach, called fuzzy association rule mining, to automatically unveil
      these associations. This paper describes the proposed methodology and illustrates
      how it can be applied to different breast cancer datasets. The obtained results
      support known associations involving the number of copies of chromosome-17, HER2
      amplification, or the expression level of estrogen and progesterone receptors in
      breast cancer patients. They also confirm the correspondence between the HER2
      status predicted by different testing methodologies (immunohistochemistry and
      fluorescence in situ hybridization). In addition, other interesting rules
      involving CDC6, SOX11, and EFEMP1 genes are identified, although further detailed
      studies are needed to statistically confirm these findings. As part of this
      study, a web platform implementing the fuzzy association rule mining approach has
      been made freely available at: http://www.genome2.ugr.es/biofar .

PMID- 22622818
TI  - Possibilities and hindrances for prevention of intimate partner violence:
      perceptions among professionals and decision makers in a Swedish medium-sized
      town.
AB  - BACKGROUND: Intimate partner violence (IPV) is a major public health problem, but
      few evidence-based prevention programs have yet been implemented. PURPOSE: This
      study explored the perceptions and beliefs of local-level decision makers, social
      and health-care professionals, and representatives from the police force
      regarding the possibilities and hindrances for prevention of IPV. METHOD: An
      explorative qualitative approach was used, and participants were strategically
      selected for focus group discussions. The participants, 19 men and 23 women, were
      professionals or decision makers within health-care services, social welfare,
      municipal administration, the police force, local industry, and local politicians
      in a Swedish town of 54,000 inhabitants. The focus group discussions were audio
      recorded, transcribed verbatim, and thematically analyzed. A manifest content
      analysis was performed on the text. RESULTS: Preschools, schools, sports
      associations, workplaces, and the mass media were suggested as possible arenas
      for prevention measures. The proposed activities included norm building and
      improved social support structures. Hindrances were conceptualized as societal
      beliefs and attitudes, shame, silence, gender inequality, the counteracting
      influence of the media, and lack of resources. The participants demonstrated
      closeness and distance to IPV, expressed as acceptance or referral of
      responsibility to others regarding where and by whom prevention measures should
      be executed. CONCLUSION: This study gave new insights in the prevailing
      perceptions of professionals and decision makers of a medium-sized Swedish town,
      which can be a useful knowledge in future preventive work and contribute to
      bridge the gap between research and practice.

PMID- 22622819
TI  - Influence of self-efficacy on compliance to workplace exercise.
AB  - BACKGROUND: Continuous neck and shoulder pain is a common musculoskeletal
      complaint. Physical exercise can reduce pain symptoms, but compliance to exercise
      is a challenge. Exercise-specific self-efficacy has been found to be a predictor
      of participation in preplanned exercise. Little is known about the influence of
      exercise-specific self-efficacy on compliance to workplace physical exercise.
      PURPOSE: To determine the influence of exercise-specific self-efficacy on
      compliance to specific strength exercises during working hours for laboratory
      technicians. METHODS: We performed a cluster-randomized controlled trial,
      including laboratory technicians from two industrial production units in
      Copenhagen, Denmark. The participants were randomized to supervised specific
      strength exercises for the neck and shoulder muscles for 20 minutes three times a
      week (n = 282) or to a reference group (n = 255). The participants answered
      baseline and follow-up questions regarding self-efficacy and registered all
      exercises in a diary. RESULTS: Overall compliance to exercises was 45 %.
      Compliance in company A (private sector) differed significantly between the three
      self-efficacy groups after 20 weeks. The odds ratio of compliance was 2.37 for
      moderate versus low self-efficacy, and 2.93 for high versus low self-efficacy. No
      significant difference was found in company B (public sector) or in the
      intervention group as a whole. CONCLUSION: We did not find self-efficacy to be a
      general statistically significant predictor of compliance to exercises during 20
      weeks, but found self-efficacy to be a predictor of compliance in a private
      sector setting. Workplace-specific differences might be present and should be
      taken into account.

PMID- 22622820
TI  - Pharmacological kinetics of BmK AS, a sodium channel site 4-specific modulator on
      Nav1.3.
AB  - OBJECTIVE: In this study, the pharmacological kinetics of Buthus martensi Karsch
      (BmK) AS, a specific modulator of voltage-gated sodium channel site 4, was
      investigated on Na(v)1.3 expressed in Xenopus oocytes. METHODS: Two-electrode
      voltage clamp was used to record the whole-cell sodium current. RESULTS: The peak
      currents of Na(v)1.3 were depressed by BmK AS over a wide range of concentrations
      (10, 100, and 500 nmol/L). Most remarkably, BmK AS at 100 nmol/L hyperpolarized
      the voltage-dependence and increased the voltage-sensitivity of steady-state
      activation/inactivation. In addition, BmK AS was capable of hyperpolarizing not
      only the fast inactivation but also the slow inactivation, with a greater
      preference for the latter. Moreover, BmK AS accelerated the time constant and
      increased the ratio of recovery in Na(v)1.3 at all concentrations. CONCLUSION:
      This study provides direct evidence that BmK AS facilitates steady-state
      activation and inhibits slow inactivation by stabilizing both the closed and open
      states of the Na(v)1.3 channel, which might result from an integrative binding to
      two receptor sites on the voltage-gated sodium channels. These results may shed
      light on therapeutics against Na(v)1.3-targeted pathology.

PMID- 22622821
TI  - Tetrahydropalmatine protects against methamphetamine-induced spatial learning and
      memory impairment in mice.
AB  - OBJECTIVE: The purpose of this study was to investigate the effect of
      methamphetamine (MA) on spatial learning and memory and the role of
      tetrahydropalmatine (THP) in MA-induced changes in these phenomena in mice.
      METHODS: Male C57BL/6 mice were randomly divided into eight groups, according to
      different doses of MA, different doses of THP, treatment with both MA and THP,
      and saline controls. Spatial learning and memory were assessed using the Morris
      water maze. Western blot was used to detect the expression of extracellular
      signal-regulated protein kinase (ERK) in the mouse prefrontal cortex (PFC) and
      hippocampus. RESULTS: Repeated MA treatment significantly increased the escape
      latency in the learning phase and decreased the number of platform site crossings
      in the memory-test phase. ERK1/2 expression was decreased in the PFC but not in
      the hippocampus of the MA-treated mice. Repeated THP treatment alone did not
      affect the escape latency, the number of platform site crossings or the total
      ERK1/2 expression in the brain. Statistically significantly shorter escape
      latencies and more platform site crossings occurred in MA+THP-treated mice than
      in MA-treated mice. CONCLUSION: Repeated MA administration impairs spatial
      learning and memory in mice, and its co-administration with THP prevents this
      impairment, which is probably attributable to changed ERK1/2 expression in the
      PFC. This study contributes to uncovering the mechanism underlying MA abuse, and
      to exploring potential therapies.

PMID- 22622822
TI  - Reactive oxidative species enhance amyloid toxicity in APP/PS1 mouse neurons.
AB  - OBJECTIVE: To investigate whether intracellular amyloid beta (iAbeta) induces
      toxicity in wild type (WT) and APP/PS1 mice, a mouse model of Alzheimer's
      disease. METHODS: Different forms of Abeta aggregates were microinjected into
      cultured WT or APP/PS1 mouse hippocampal neurons. TUNEL staining was performed to
      examine neuronal cell death. Reactive oxidative species (ROS) were measured by
      MitoSOXRed mitochondrial superoxide indicator. RESULTS: Crude, monomer and
      protofibril Abeta induced more toxicity in APP/PS1 neurons than in WT neurons.
      ROS are involved in mediating the vulnerability of APP/PS1 neurons to iAbeta
      toxicity. CONCLUSION: Oxidative stress may mediate cell death induced by iAbeta
      in neurons.

PMID- 22622823
TI  - Personality correlates of reporting Chinese words from the Deutsch "high-low"
      word illusion by Chinese-speaking people.
AB  - OBJECTIVE: When English-speaking people listen to the Deutsch "high-low" word
      illusion, they report hearing English words. Whether Chinese-speaking people
      report Chinese words when listening to the illusion, or whether any reported
      words might be correlated with personality traits as previous investigations have
      demonstrated for listening to music in other cultures, is open to question. The
      present study aimed to address this. METHODS: A total of 308 right-handed,
      healthy volunteers (177 women and 131 men) were given the illusion test and asked
      to answer the Zuckerman-Kuhlman personality questionnaire (ZKPQ). Their
      depressive tendency was measured by the Plutchik-van Praag depression inventory
      (PVP). RESULTS: There was no gender effect regarding either the PVP score or the
      number of reported Chinese words from the illusion. Women scored higher on ZKPQ
      neuroticism-anxiety than men. The number of meaningful Chinese words reported was
      correlated with the ZKPQ impulsive sensation-seeking, aggression-hostility, and
      activity scores. Some words reported by participants who scored higher on these
      three traits were related in meaning to those scales. CONCLUSION: Our preliminary
      results suggest that when Chinese-speaking people listen to the Deutsch "high
      low" word illusion, they might use personality-related, specific cognitive
      schemata.

PMID- 22622824
TI  - QT wave dispersion in patients with panic disorder.
AB  - OBJECTIVE: QT dispersion (QTd), defined as the maximal inter-lead difference in
      QT intervals on 12 leads of the surface electrocardiogram (ECG), reflects the
      regional heterogeneity of ventricular repolarization and has been suggested as an
      important marker for risk of arrhythmia in addition to the QT interval. Some
      investigators proposed that it might be a predisposing factor for arrhythmic
      events and sudden death. Thus, we aimed to investigate whether QTd differs in
      patients with panic disorder from that in healthy controls. METHODS: In 40 panic
      disorder patients and 40 healthy controls, Q(max), Q(min), and QTd values were
      measured. In addition, the Hamilton depression rating scale and the panic
      agoraphobia scale were scored for both patients and healthy volunteers. RESULTS:
      Q(max) and Q(min) values in the panic disorder patients were significantly higher
      than those in healthy controls. The mean corrected QTd was significantly greater
      in the patients than in the controls. One-way analysis of covariance (ANCOVA;
      using left atrial size, age and heart rate as covariates) also corrected the
      significant difference. In addition, ANCOVA revealed a significant main effect
      for the diagnosis, indicating a significantly higher QTd for patients compared
      with controls. CONCLUSION: QTd might be associated with panic disorder. Future
      studies in larger samples evaluating the effects of treatment are required.

PMID- 22622825
TI  - Curcumin protects nigral dopaminergic neurons by iron-chelation in the 6
      hydroxydopamine rat model of Parkinson's disease.
AB  - OBJECTIVE: Curcumin is a plant polyphenolic compound and a major component of
      spice turmeric (Curcuma longa). It has been reported to possess free radical
      scavenging, iron-chelating, and anti-inflammatory properties in different
      tissues. Our previous study showed that curcumin protects MES23.5 dopaminergic
      cells from 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in vitro. The present
      study aimed to explore this neuroprotective effect in the 6-OHDA-lesioned rat
      model of Parkinson's disease in vivo. METHODS: Rats were given intragastric
      curcumin for 24 days. 6-OHDA lesioning was conducted on day 4 of curcumin
      treatment. Dopamine content was assessed by high-performance liquid
      chromatography with electrochemical detection, tyrosine hydroxylase (TH)
      containing neurons by immunohistochemistry, and iron-containing cells by Perls'
      iron staining. RESULTS: The dopamine content in the striatum and the number of TH
      immunoreactive neurons decreased after 6-OHDA treatment. Curcumin pretreatment
      reversed these changes. Further studies demonstrated that 6-OHDA treatment
      increased the number of iron-staining cells, which was dramatically decreased by
      curcumin pretreatment. CONCLUSION: The protective effects of curcumin against 6
      OHDA may be attributable to the iron-chelating activity of curcumin to suppress
      the iron-induced degeneration of nigral dopaminergic neurons.

PMID- 22622826
TI  - Characterization of amyloid-beta precursor protein intracellular domain
      associated transcriptional complexes in SH-SY5Y neurocytes.
AB  - OBJECTIVE: Alzheimer's disease (AD) is one of the major disorders worldwide.
      Recent research suggests that the amyloid-beta precursor protein intracellular
      domain (AICD) is a potential contributor to AD development and progression. The
      small AICD is rapidly degraded after processing from the full-length protein. The
      present study aimed to apply a highly efficient biotinylation approach in vitro
      to study AICD-associated complexes in neurocytes. METHODS: By co-expressing
      Escherichia coli biotin ligase with biotinyl-tagged AICD in the SH-SY5Y neuronal
      cell line, the effects of AICD overexpression on cell proliferation and apoptosis
      were analyzed. Besides, AICD-associated nuclear transcriptional complexes were
      purified and then examined by mass spectrometry. RESULTS: Our data showed that
      AICD overexpression not only affected cell proliferation but also led to
      apoptosis in differentiated SH-SY5Y cells. Moreover, biotinylation allowed single
      step purification of biotinylated AICD-associated complexes from total nuclear
      extract via high-affinity biotin-streptavidin binding. Following this by mass
      spectrometry, we identified physically associated proteins, some reported
      previously and other novel binding partners, CUX1 and SPT5. CONCLUSION: Based on
      these results, a map of the AICD-associated nuclear interactome was depicted.
      Specifically, AICD can activate CUX1 transcriptional activity, which may be
      associated with AICD-dependent neuronal cell death. This work helps to understand
      the AICD-associated biological events in AD progression and provides novel
      insights into the development of AD.

PMID- 22622828
TI  - Possible novel roles of poly(rC)-binding protein 1 in SH-SY5Y neurocytes: an
      analysis using a dynamic Bayesian network.
AB  - OBJECTIVE: Poly(rC)-binding protein 1 (PCBP1) belongs to the heterogeneous
      nuclear ribonucleoprotein family and participates in transcriptional and
      translational regulation. Previous work has identified transcripts targeted by
      both knockdown and overexpression of PCBP1 in SH-SY5Y neuroblastoma cells using a
      microarray or ProteomeLab protein fractionation 2-dimensions (PF-2D) and
      quadrupole time-of-flight mass spectrometer. The present study aimed to further
      determine whether these altered transcripts from major pathways (such as Wnt
      signaling, TGF-beta signaling, cell cycling, and apoptosis) and two other genes,
      H2AFX and H2BFS (screened by PF-2D), have spatial relationships. METHODS: The
      genes were studied by qRT-PCR, and dynamic Bayesian network analysis was used to
      rebuild the coordination network of these transcripts. RESULTS: PCBP1 controlled
      the expression or activity of the seven transcripts. Moreover, PCBP1 indirectly
      regulated MAP2K2, FOS, FST, TP53 and WNT7B through H2AFX or regulated these genes
      through SAT. In contrast, TP53 and WNT7B are regulated by other genes.
      CONCLUSION: The seven transcripts and PCBP1 are closely associated in a spatial
      interaction network.

PMID- 22622827
TI  - SK channels modulate the excitability and firing precision of projection neurons
      in the robust nucleus of the arcopallium in adult male zebra finches.
AB  - OBJECTIVE: Motor control is encoded by neuronal activity. Small conductance
      Ca(2+)-activated K(+) channels (SK channels) maintain the regularity and
      precision of firing by contributing to the afterhyperpolarization (AHP) of the
      action potential in mammals. However, it is not clear how SK channels regulate
      the output of the vocal motor system in songbirds. The premotor robust nucleus of
      the arcopallium (RA) in the zebra finch is responsible for the output of song
      information. The temporal pattern of spike bursts in RA projection neurons is
      associated with the timing of the acoustic features of birdsong. METHODS: The
      firing properties of RA projection neurons were analyzed using patch clamp whole
      cell and cell-attached recording techniques. RESULTS: SK channel blockade by
      apamin decreased the AHP amplitude and increased the evoked firing rate in RA
      projection neurons. It also caused reductions in the regularity and precision of
      firing. RA projection neurons displayed regular spontaneous action potentials,
      while apamin caused irregular spontaneous firing but had no effect on the firing
      rate. In the absence of synaptic inputs, RA projection neurons still had
      spontaneous firing, and apamin had an evident effect on the firing rate, but
      caused no significant change in the firing regularity, compared with apamin
      application in the presence of synaptic inputs. CONCLUSION: SK channels
      contribute to the maintenance of firing regularity in RA projection neurons which
      requires synaptic activity, and consequently ensures the precision of song
      encoding.

PMID- 22622829
TI  - Dorsal and ventral streams across sensory modalities.
AB  - In this review, we describe the current models of dorsal and ventral streams in
      vision, audition and touch. Available theories take their first steps from the
      model of Milner and Goodale, which was developed to explain how human actions can
      be efficiently carried out using visual information. Since then, similar concepts
      have also been applied to other sensory modalities. We propose that advances in
      the knowledge of brain functioning can be achieved through models explaining
      action and perception patterns independently from sensory modalities.

PMID- 22622830
TI  - IL-1beta: an important cytokine associated with febrile seizures?
AB  - Febrile seizures (FSs) are the most common convulsions in childhood. Studies have
      demonstrated a significant relationship between a history of prolonged FSs during
      early childhood and temporal sclerosis, which is responsible for intractable
      mesial temporal lobe epilepsy. It has been shown that interleukin-1beta (IL
      1beta) is intrinsically involved in the febrile response in children and in the
      generation of FSs. We summarize the gene polymorphisms, changes of IL-1beta
      levels and the putative role of IL-1beta in the generation of FSs. IL-1beta could
      play a role either in enhancing or in reducing neural excitability. If the
      enhancing and reducing effects are balanced, an FS does not occur. When the
      enhancing effect plays the leading role, an FS is generated. A mild imbalance can
      cause simple FSs while a severe imbalance can cause complex FSs and febrile
      status epilepticus. Therefore, anti-IL-1beta therapy may help to treat FSs.

PMID- 22622831
TI  - Planar cell polarity genes, Celsr1-3, in neural development.
AB  - flamingo is among the 'core' planar cell-polarity genes, protein of which belongs
      to a unique cadherin subfamily. In contrast to the classic cadherins, composed of
      several extracellular cadherin repeats, one transmembrane domain and one
      cytoplasmic segment linked to catenin binding, Drosophila Flamingo has seven
      transmembrane segments and a cytoplasmic tail with no catenin-binding sequence.
      In Drosophila, Flamingo has pleotropic roles in controlling epithelial polarity
      and neuronal morphogenesis. Three mammalian orthologs of flamingo, Celsr1-3, are
      widely expressed in the nervous system. Recent work has shown that Celsr1-3 play
      important roles in neural development, such as in axon guidance, neuronal
      migration, and cilium polarity. Celsr1-3 single-gene knockout mice exhibit
      different phenotypes, but there are cooperative interactions among these genes.

PMID- 22622832
TI  - Hypoxic preconditioning in an autohypoxic animal model.
AB  - Hypoxic preconditioning refers to the exposure of organisms, systems, organs,
      tissues or cells to moderate hypoxia/ischemia that results in increased
      resistance to a subsequent episode of severe hypoxia/ischemia. In this article,
      we review recent research based on a mouse model of repeated exposure to
      autohypoxia. Pre-exposure markedly increases the tolerance to or protection
      against hypoxic insult, and preserves the cellular structure of the brain.
      Furthermore, the hippocampal activity amplitude and frequency of
      electroencephalogram, latency of cortical somatosensory-evoked potential and
      spinal somatosensory-evoked potential progressively decrease, while spatial
      learning and memory improve. In the brain, detrimental neurochemicals such as
      free radicals are down-regulated, while beneficial ones such as adenosine are up
      regulated. Also, antihypoxia factor(s) and gene(s) are activated. We propose that
      the tolerance and protective effects depend on energy conservation and plasticity
      triggered by exposure to hypoxia via oxygen-sensing transduction pathways and
      hypoxia-inducible factor-initiated cascades. A potential path for further
      research is the development of devices and pharmaceuticals acting on antihypoxia
      factor(s) and gene(s) for the prevention and treatment of hypoxia and related
      syndromes.

PMID- 22622833
TI  - Correspondence regarding genetic assessment following increased nuchal
      translucency and normal karyotype.

PMID- 22622835
TI  - Referral patterns for microarray testing in prenatal diagnosis.

PMID- 22622836
TI  - Purification and characterization of a novel extracellular inulinase from a new
      yeast species Candida kutaonensis sp. nov. KRF1(T).
AB  - A novel extracellular exoinulinase was purified and characterized from a new
      yeast strain KRF1(T), and the gene encoding the enzyme was successfully cloned.
      The enzyme was stable at low pH between 3.0 and 6.5. The K (m) and V (max) values
      of the purified enzyme for inulin were 2.3 mg/mL and 4.8 mg/min, respectively.
      The optimum temperature of the inulinase was 50  degrees C, and the enzyme
      remained 78 % of activity at 60  degrees C for 2 h. The inulinase showed an amino
      acid sequence identity of 58 % to its closest homolog in Meyerozyma (Pichia)
      guilliermondii. In the secondary structure, the domain G (VMEVH) of the enzyme
      contained three unique residues (V, M, and H). Compared with previously reported
      inulinases, the enzyme from strain KRF1(T) displayed strong acid resistance,
      notable thermostability, and high affinity for the substrate of inulin. Based on
      sequence analysis of the 26S rDNA D1/D2 domain and phenotypic characterization,
      the yeast strain KRF1(T) was found to represent a novel anamorphic, ascomycetous
      yeast species. A complete description of the species is given and the name
      Candida kutaonensis sp. nov (type strain = KRF1(T) = AS 2.4027(T) = CBS 11388(T))
      is proposed.

PMID- 22622837
TI  - Impact of plant derivatives on the growth of foodborne pathogens and the
      functionality of probiotics.
AB  - Numerous studies have been published on the antimicrobial and antioxidant
      properties of various plant components. However, there is relatively little
      information on the impact of such components on the enhancement of probiotics and
      production of antimicrobial compounds from these probiotics. Hence, this paper
      focuses on the influence of plant-derived components against pathogens,
      enhancement of cell viability and functionality of probiotics, and potential
      applications of such components in food safety and human health.

PMID- 22622838
TI  - Endophytic fungi: novel sources of anticancer lead molecules.
AB  - Cancer is a major killer disease all over the world and more than six million new
      cases are reported every year. Nature is an attractive source of new therapeutic
      compounds, as a tremendous chemical diversity is found in millions of species of
      plants, animals, and microorganisms. Plant-derived compounds have played an
      important role in the development of several clinically useful anti-cancer
      agents. These include vinblastine, vincristine, camptothecin, podophyllotoxin,
      and taxol. Production of a plant-based natural drug is always not up to the
      desired level. It is produced at a specific developmental stage or under specific
      environmental condition, stress, or nutrient availability; the plants may be very
      slow growing taking several years to attain a suitable growth phase for product
      accumulation and extraction. Considering the limitations associated with the
      productivity and vulnerability of plant species as sources of novel metabolites,
      microorganisms serve as the ultimate, readily renewable, and inexhaustible source
      of novel structures bearing pharmaceutical potential. Endophytes, the
      microorganisms that reside in the tissues of living plants, are relatively
      unstudied and offer potential sources of novel natural products for exploitation
      in medicine, agriculture and the pharmaceutical industry. They develop special
      mechanisms to penetrate inside the host tissue, residing in mutualistic
      association and their biotransformation abilities opens a new platform for
      synthesis of novel secondary metabolites. They produce metabolites to compete
      with the epiphytes and also with the plant pathogens to maintain a critical
      balance between fungal virulence and plant defense. It is therefore necessary
      that the relationship between the plants and endophytes during the accumulation
      of these secondary metabolites is studied. Insights from such research would
      provide alternative methods of natural product drug discovery which could be
      reliable, economical, and environmentally safe.

PMID- 22622839
TI  - Transcriptomic studies of phosphate control of primary and secondary metabolism
      in Streptomyces coelicolor.
AB  - Phosphate controls the biosynthesis of many classes of secondary metabolites that
      belong to different biosynthetic groups, indicating that phosphate control is a
      general mechanism governing secondary metabolism. We refer in this article to the
      molecular mechanisms of regulation, mediated by the two-component system PhoR
      PhoP, of the primary metabolism and the biosynthesis of antibiotics. The two
      component PhoR-PhoP system is conserved in all Streptomyces and related
      actinobacteria sequenced so far, and involves a third component PhoU that
      modulates the signal transduction cascade. The PhoP DNA-binding sequence is well
      characterized in Streptomyces coelicolor. It comprises at least two direct repeat
      units of 11 nt, the first seven of which are highly conserved. Other less
      conserved direct repeats located adjacent to the core ones can also be bound by
      PhoP through cooperative protein-protein interactions. The phoR-phoP operon is
      self-activated and requires phosphorylated PhoP to mediate the full response.
      About 50 up-regulated PhoP-dependent genes have been identified by comparative
      transcriptomic studies between the parental S. coelicolor M145 and the DeltaphoP
      mutant strains. The PhoP regulation of several of these genes has been studied in
      detail using EMSA and DNase I footprinting studies as well as in vivo expression
      studies with reporter genes and RT-PCR transcriptomic analyses.

PMID- 22622840
TI  - Production of biogas from solid organic wastes through anaerobic digestion: a
      review.
AB  - Anaerobic digestion treatments have often been used for biological stabilization
      of solid wastes. These treatment processes generate biogas which can be used as a
      renewable energy sources. Recently, anaerobic digestion of solid wastes has
      attracted more interest because of current environmental problems, most
      especially those concerned with global warming. Thus, laboratory-scale research
      on this area has increased significantly. In this review paper, the summary of
      the most recent research activities covering production of biogas from solid
      wastes according to its origin via various anaerobic technologies was presented.

PMID- 22622841
TI  - Step-by-step strategy for protein enrichment and proteome characterisation of
      extracellular polymeric substances in wastewater treatment systems.
AB  - Extracellular polymeric substances (EPS) are keys in biomass aggregation and
      settleability in wastewater treatment systems. In membrane bioreactors (MBR), EPS
      are an important factor as they are considered to be largely responsible for
      membrane fouling. Proteins were shown to be the major component of EPS produced
      by activated sludge and to be correlated with the properties of the sludge, like
      settling, hydrophobicity and cell aggregation. Previous EPS proteomic studies of
      activated sludge revealed several problems, like the interference of other EPS
      molecules in protein analysis. In this study, a successful strategy was outlined
      to identify the proteins from soluble and bound EPS extracted from activated
      sludge of a lab-scale MBR. EPS samples were first subjected to pre-concentration
      through lyophilisation, centrifugal ultrafiltration or concentration with a
      dialysis membrane coated by a highly absorbent powder of polyacrylate
      polyalcohol, preceded or not by a dialysis step. The highest protein
      concentration factors were achieved with the highly absorbent powder method
      without previous dialysis step. Four protein precipitation methods were then
      tested: acetone, trichloroacetic acid (TCA), perchloric acid and a commercial
      kit. Protein profiles were compared in 4-12 % sodium dodecyl sulphate
      polyacrylamide gel electrophoresis gels. Both acetone and TCA should be applied
      for the highest coverage for soluble EPS proteins, whereas TCA was the best
      method for bound EPS proteins. All visible bands of selected profiles were
      subjected to mass spectrometry analysis. A high number of proteins (25-32 for
      soluble EPS and 17 for bound EPS) were identified. As a conclusion of this study,
      a workflow is proposed for the successful proteome characterisation of soluble
      and bound EPS from activated sludge samples.

PMID- 22622843
TI  - Bickerstaff's brainstem encephalitis presenting to the ICU.
AB  - BACKGROUND: Bickerstaff's brainstem encephalitis continues to pose a diagnostic
      and treatment challenge since the original descriptions by Bickerstaff and Miller
      Fisher. The clinical syndrome overlaps with AIDP and MFS, but is accompanied by
      decreased level of consciousness not attributable to other causes, and the
      variable presence of long-tract signs. METHODS: The methods in this study include
      the case presentation with autopsy findings of an elderly male presented with
      progressive weakness and impairment of consciousness and the literature review.
      RESULTS: Examination revealed areflexia and loss of most brainstem reflexes. Some
      improvement occurred after several weeks in the ICU, prior to death from
      pulmonary embolism. Pathologic specimens were similar to others in the
      literature, with inflammatory changes in nerve roots and brainstem. CONCLUSIONS:
      The above findings led us to conclude that Bickerstaff's brainstem encephalitis
      remains a clinical diagnosis despite advances in electrophysiologic testing and
      neuroimaging. BBE likely represents part of a spectrum, overlapping with AIDP and
      MFS. Immunomodulation may be helpful in shortening the clinical course.

PMID- 22622844
TI  - [General practitioner or specialist at home or abroad?].
AB  - This study investigated the career preferences of medical graduates in Germany
      with regard to discipline, place and position after the completion of
      postgraduate training. We also investigated differences in career options
      according to gender and region of study (former German Federal Republic vs.
      former German Democratic Republic).The study is based on a standardised postal
      survey among all last year medical students in the medical faculties of Erlangen,
      Giessen, Hamburg, Heidelberg, Cologne, Leipzig and Magdeburg in 2009. 2 107
      persons were contacted and 1 012 (48%) participated in the survey.96% of
      participants stated their intention to pursue a postgraduate training in a
      medical discipline, and only 0.4% denied such an objective. 7% of the graduates
      preferred a career towards general practice, and a similar percentage preferred
      general internal medicine which usually also leads to a primary care activity.
      84% aimed at becoming a medical specialist. In total, 28% intended to work in a
      specialist practice, and 10% in a general practice. Only one-fifth of the latter
      aimed at working in a countryside setting. 7% aimed at starting postgraduate
      training outside of Germany, and 8% preferred to work outside Germany after
      completion of the postgraduate training. In both cases, Switzerland was by far
      the most preferred country.The results contradict the thesis that young graduates
      are reluctant to enter clinical medicine. Working abroad is within the scope of
      less than 10% of the graduates. A dramatic difference between the demand for
      general practitioners and the career intentions of medical graduates is observed.
      Measures to increase the attractiveness of primary care, especially in the
      countryside, are urgently needed.

PMID- 22622845
TI  - The influence of time and adaptation on health state valuations in patients with
      spinal cord injury.
AB  - OBJECTIVES: One of the explanations for the difference between health state
      utilities elicited from patients and the public--often provided but seldom
      studied--is adaptation. The influence of adaptation on utilities was investigated
      in patients with spinal cord injury. METHODS: Interviews were held at 3 time
      points (T1, after admission to the rehabilitation center; T2, during active
      rehabilitation; T3, at least half a year after discharge). At T1, 60 patients
      were interviewed; 10 patients withdrew at T2 and T3. At all time points, patients
      were asked to value their own health and a health state description of rheumatoid
      arthritis on a time trade-off and a visual analogue scale. The Barthel Index, a
      measure of independence from help in activities of daily living, and the
      adjustment ladder were filled out. Main analyses were performed using mixed
      linear models taking the time-dependent covariates (Barthel Index and adjustment
      ladder) into account. RESULTS: Time trade-off valuations for patients' own health
      changed over time, even after correction for gain in independence from help in
      activities of daily living, F(2, 59) = 8.86, P < 0.001. This change was related
      to overall adaptation. Both a main effect for adaptation, F(87, 1) = 10.05; P =
      0.002, and an interaction effect between adaptation and time, F(41, 1)= 4.10, P =
      0.024, were seen for time trade-off valuations. Valuations given for one's own
      health on the visual analogue scale did not significantly change over time, nor
      did the valuations for the hypothetical health state. CONCLUSION: Patients'
      health state valuations change over time, over and above the change expected by
      the rehabilitation process, and this change is partly explained by adaptation.
      Experience with a chronic illness did not lead to change in valuations of
      hypothetical health states.

PMID- 22622846
TI  - Information distortion in physicians' diagnostic judgments.
AB  - BACKGROUND: Information distortion suggests that people change the evaluation of
      new information to support an emerging belief. The present study was designed to
      measure the extent to which physicians distort incoming medical information to
      support an emerging diagnosis. DESIGN: Data were collected via an anonymous
      questionnaire. The experimental group (102 physicians) read 3 patient scenarios,
      each with 2 competing diagnoses. Physicians first read information that favored 1
      of the 2 diagnoses (the "steer"). They then rated a series of neutral cues that
      favored neither diagnosis. At each cue presentation, respondents rated the extent
      to which cues favored either diagnosis and updated the strength of their
      diagnostic belief. After the neutral cues in the third scenario, respondents
      rated cues that opposed the initial steer. A control group (36 physicians) rated
      all the cues in random order and not within scenarios, thus providing unbiased
      baseline ratings for calculating distortion in the experimental group. RESULTS:
      Distortion was statistically significant (P < 0.001) and was associated with the
      strength of belief in the leading diagnosis. Physicians with over 10 years in
      practice distorted less than their less experienced counterparts (
      $$?overline{X}$$ = 1.04 v. $$?overline{X}$$ = 1.78, P < 0.05). Having developed
      an initial diagnostic leaning consistent with the steer, 56% of physicians
      remained committed to it after receiving the conflicting cues. Distortion was
      strongly associated with commitment to the steer (odds ratio, 1.4; 95% confidence
      interval, 1.03-1.79; P = 0.03). LIMITATIONS: Physicians did not elicit
      information; therefore, the authors cannot estimate the size of distortion in
      tasks involving information search. CONCLUSIONS: Distortion could partly explain
      commitment of physicians to an early diagnosis. Both distortion and strength of
      initial diagnostic belief seem to decline after 10 years in family medicine.

PMID- 22622847
TI  - CCR7-independent transport of skin antigens occurs in the dermis.
AB  - Under homeostatic conditions, skin DCs migrate to regional LNs transporting self
      antigens (self-Ags). The transport of self-Ags is considered to be critical for
      maintaining peripheral tolerance. Although the chemokine receptor CCR7 potently
      induces the migration of skin DCs to regional LNs, Ccr7(-/-)  (Ccr7-KO) mice do
      not show skin auto-immune diseases. To resolve this inconsistency, we examined
      Ccr7-KO epidermis- or dermis-hyperpigmented transgenic (Tg) mice, in which the
      transport of skin self-Ags is traceable by melanin granules (MGs). Under CCR7
      deficient conditions, the transport of epidermal MGs to regional LNs was impaired
      at 7 weeks of age. However, epidermal MGs could be transported when they had
      accumulated in the dermis. Ccr7-KO-dermis-pigmented Tg mice confirmed the
      presence of CCR7-independent transport from the dermis. Compared with WT-dermis
      pigmented Tg mice, the amount of transported melanin and number of MG-laden
      CD11c(+)  cells were both approximately 40% of the WT levels, while the number of
      MG-laden CD205(+)  or CD207(+)  cells decreased to about 10% in skin regional LNs
      of Ccr7-KO-dermis-pigmented Tg mice. Cell sorting highlighted the involvement of
      CD11c(+)  cells in the CCR7-independent transport. Here, we show that CCR7
      independent transport of skin self-Ags occurs in the dermis. This system might
      contribute to the continuous transport of self-Ags, and maintain peripheral
      tolerance.

PMID- 22622848
TI  - Iodide-assisted total lead measurement and determination of different lead
      fractions in drinking water samples.
AB  - Lead and its compounds are toxic and can harm human health, especially the
      intelligence development in children. Accurate measurement of total lead present
      in drinking water is crucial in determining the extent of lead contamination and
      human exposure due to drinking water consumption. The USEPA method for total lead
      measurement (no. 200.8) is often used to analyze lead levels in drinking water.
      However, in the presence of high concentration of the tetravalent lead corrosion
      product PbO(2), the USEPA method was not able to fully recover particulate lead
      due to incomplete dissolution of PbO(2) particles during strong acid digestion.
      In this study, a new procedure that integrates membrane separation, iodometric
      PbO(2) measurement, strong acid digestion and ICP-MS measurement was proposed and
      evaluated for accurate total lead measurement and quantification of different
      lead fractions including soluble Pb(2+), particulate Pb(II) carbonate and PbO(2)
      in drinking water samples. The proposed procedure was evaluated using drinking
      water reconstituted with spiked Pb(2+), spiked particulate Pb(II) carbonate and
      in situ formed or spiked PbO(2). Recovery tests showed that the proposed
      procedure and the USEPA method can achieve 93-112% and 86-103% recoveries
      respectively for samples containing low PbO(2) concentrations (0.018-0.076 mg Pb
      per L). For samples containing higher concentrations of PbO(2) (0.089-1.316 mg Pb
      per L), the USEPA method failed to meet the recovery requirement for total lead
      (85-115%) while the proposed method can achieve satisfactory recoveries (91-111%)
      and differentiate the soluble Pb(2+), particulate Pb(II) carbonate and PbO(2).

PMID- 22622849
TI  - Botox((r)) for idiopathic overactive bladder: efficacy, duration and safety.
      Effectiveness of subsequent injection.
AB  - PURPOSE: To test the efficacy, duration and safety of 100 U of botulinum toxin
      type A (BoNT/A) in women affected by idiopathic detrusor overactivity (IDO) and
      the effectiveness of subsequent injections. METHODS: In this double centre,
      prospective study conducted from March 2008 to March 2010, we selected women
      affected by IDO who failed to respond to various antimuscarinic agents, reported
      intolerable anticholinergic side-effects or contraindication to their use, also
      without any response to tibial stimulation. Medical history, physical
      examination, standard urodynamic examination, urinalysis, urine culture, a 4-day
      voiding diary and a quality of life questionnaire were requested for all
      patients. A total amount of 100 U of BoNT/A were injected into the detrusor
      muscle. A second injection of BoNT/A was suggested to patients who experienced a
      relapse of initially improved symptoms. RESULTS: We enrolled a total number of 68
      women. All patients showed significant improvement in urodynamic parameters,
      clinical features and quality of life, after the first injection of Botox((r))
      until the 9 months of follow-up. Even after the second injection, with a follow
      up of 3 months, we obtained results comparable with the first injection. Side
      effects include an increase in post-void residual volume, dysuria and urinary
      infections. CONCLUSIONS: We considered the dose of 100 U of Botox((r)), for
      treatment of IDO, as an efficacious and safe solution compared to other
      therapeutic options, without serious and lasting adverse effects for women, even
      after a second injection.

PMID- 22622850
TI  - Sonographic evaluation of kidney parenchymal growth in the fetus.
AB  - OBJECTIVE: The aim of the study was to establish a nomogram for renal parenchymal
      thickness throughout pregnancy. METHODS: One-hundred and twenty-eight healthy
      women with singleton, well-dated, uncomplicated second- or third-trimester
      pregnancies were prospectively evaluated for renal parenchymal thickness on
      routine ultrasound scans. The renal parenchyma was measured in transverse and
      sagittal sections using predefined criteria. RESULTS: There were no differences
      in anterior or posterior parenchymal measurements in either plane by fetal sex.
      On sagittal-section analysis, no differences were noted between the right and
      left kidneys. A nomogram was established on the basis of the findings. The
      results showed constant linear growth of the fetal parenchyma during pregnancy.
      CONCLUSIONS: The normal fetal parenchyma grows at a constant, linear rate
      throughout pregnancy. The nomogram formulated may serve as a basis of future
      studies of the correlation of parenchymal thickness with postnatal kidney
      function in fetuses with urinary tract anomalies.

PMID- 22622851
TI  - Prevention of infectious morbidity after elective abdominal hysterectomy.
AB  - OBJECTIVE: Our aim was to investigate whether posthysterectomy infectious
      morbidity could be reduced by intravaginal therapy before operations. MATERIALS
      AND METHODS: Women expected to undergo elective total abdominal hysterectomy were
      included. Vaginal flora was evaluated by preoperative Gram-stained vaginal smears
      up to Nugent's criteria. Study group were administered vaginal combination
      therapy including 500 mg metronidazole and 100 mg miconazole nitrate two times a
      day for 7 days. Control group were not given any preoperative vaginal therapy.
      Postoperative infectious morbidity was evaluated and compared. RESULTS: Ninety
      five women in the study group and 97 women in the control group completed the
      study protocol. Women with abnormal flora had significantly more wound and
      vaginal cuff infections than the women with normal flora in the control group.
      Urinary infections were significantly higher in the study group (38.9 vs. 23.7 %)
      and vaginal cuff infections were significantly higher in the untreated control
      group (2.1 vs. 8.2 %). CONCLUSIONS: We concluded that postoperative vaginal cuff
      infections can be decreased by treating abnormal vaginal flora before elective
      abdominal hysterectomies.

PMID- 22622852
TI  - Pain management after cesarean: a randomized controlled trial of oxycodone versus
      intravenous piritramide.
AB  - PURPOSE: Primary objective was to assess whether oral analgesia with oxycodone
      offers superior pain relief after cesareans than patient controlled analgesia
      (PCA). Secondary outcomes were additional pain medication, time to first
      mobilization, therapeutic side effects, postoperative restrictions, overall
      satisfaction and costs. MATERIALS AND METHODS: Randomized controlled trial at a
      University Hospital conduct between July 2009 and November 2009. Of the 1,112
      patients, 257 met the inclusion criteria and 239 agreed to participate. Patients
      were randomly assigned to either receive intravenous piritramide PCA (2 mg
      piritramide/ml 0.9 % saline) or oral oxycodone (20 mg). Pain was assessed on a
      visual analog pain scale (VAS) at 2, 12, 24, 32, 40, 48 and 72 h after cesarean.
      RESULTS: No differences in VAS scores were observed within the general study
      population. Pain scores of oxycodone versus PCA were comparable at 24 h. Patients
      randomized to PCA demonstrated increased demand for rescue medication 48 h after
      cesarean (p = 0.057). In the PCA group, patients with previous cesarean had
      increased operative times, a trend towards increased VAS scores after 48 h (p =
      0.081) and increased VAS scores in comparison to patients who did not have
      cesarean before (p = 0.044). For this subgroup, no difference was seen in the
      oxycodone patients (p = 0.883). CONCLUSION: General satisfaction with both
      treatment regimes was high. The results support the potential use of oral pain
      regimes and emphasis the importance of a multimodal approach to treat post
      cesarean pain. Oral oxycodone is a not expensive, convenient and comparable
      analgesic to PCA devices with opioids after cesarean. Trial registration at
      clinicaltrials.gov identifier: NCT 01115101.

PMID- 22622853
TI  - Factors affecting operative blood loss from open radical hysterectomy and pelvic
      lymphadenectomy for early-stage cervical cancer.
AB  - PURPOSE: To evaluate the effect of clinical and tumor factors on operative blood
      loss during open radical hysterectomy and pelvic lymphadenectomy for early-stage
      cervical cancer. METHODS: Clinical, pathological, and operative data of 456 women
      with cervical cancer stage IA2-IIA who had open radical hysterectomy with
      bilateral pelvic lymphadenectomy (RHPL) from January 2003 to December 2005 were
      reviewed with regard to operative blood loss of 600 ml or more. RESULTS: Parity
      (RR 1.67; 95 % CI 1.02-2.73; p value 0.04) and salpingo-oophorectomy (RR 1.57; 95
      % CI 1.06-2.31; p value 0.02) were statistically associated with operative blood
      loss of 600 ml or more from multivariate analysis. Preoperative chemotherapy (RR
      1.87; 95 % CI 1.18-2.96; p value < 0.01) and BMI >= 25 kg/m(2) (RR 1.73; 95 % CI
      1.08-2.75; p value 0.02) were significantly associated with blood loss of more
      than 1,000 ml in the multivariate analysis. CONCLUSION: High parity (3 or more)
      and incidental salpingo-oophorectomy are related to an increased risk of
      operative blood loss of 600 ml or more during open RHPL. However, the effects
      were marginal and no clear explanation for the underlying mechanisms is
      available. Preoperative chemotherapy and overweight were independent predictors
      of operative blood loss of more than 1,000 ml.

PMID- 22622855
TI  - Quality of life and mental health comparisons among liver transplant recipients
      and cirrhotic patients with different self-perceptions of health.
AB  - Our aim was to analyze the differences in quality of life and mental health among
      liver transplant recipients with better (G(1)) and worse (G(2)) perceived health
      and decompensated cirrhotic patients (G(3)). We selected two groups of patients:
      168 liver transplant recipients and 75 cirrhotic patients. The Hospital Anxiety
      and Depression Scale and SF-36 Health Survey were used. Statistically significant
      differences showed that cirrhotic patients (G(3)) suffered the highest
      impairment, and liver transplant recipients with better self-perceived health
      (G(1)) had the lowest impairment, whereas patients with worse self-perceived
      health (G(2)) were in an intermediate position between both groups. Moreover,
      very striking differences, based on large effect sizes, were found among groups
      on some quality of life dimensions: physical-role, general health, vitality, and
      physical functioning. In conclusion, the biopsychosocial well-being of liver
      transplant recipients is better than that of cirrhotic patients, even if the
      former do not perceive their health positively.

PMID- 22622856
TI  - Extracranial internal carotid artery vasospasm due to sympathetic dysfunction.

PMID- 22622857
TI  - Phosphorylation prevents polyglucosan transport in Lafora disease.

PMID- 22622858
TI  - Reducing in-hospital delay to 20 minutes in stroke thrombolysis.
AB  - OBJECTIVES: Efficacy of thrombolytic therapy for ischemic stroke decreases with
      time elapsed from symptom onset. We analyzed the effect of interventions aimed to
      reduce treatment delays in our single-center observational series. METHODS: All
      consecutive ischemic stroke patients treated with IV alteplase (tissue
      plasminogen activator [tPA]) were prospectively registered in the Helsinki Stroke
      Thrombolysis Registry. A series of interventions to reduce treatment delays were
      implemented over the years 1998 to 2011. In-hospital delays were analyzed as
      annual median door-to-needle time (DNT) in minutes, with interquartile range.
      RESULTS: A total of 1,860 patients were treated between June 1995 and June 2011,
      which included 174 patients with basilar artery occlusion (BAO) treated mostly
      beyond 4.5 hours from symptom onset. In the non-BAO patients, the DNT was reduced
      annually, from median 105 minutes (65-120) in 1998, to 60 minutes (48-80) in
      2003, further on to 20 minutes (14-32) in 2011. In 2011, we treated with tPA 31%
      of ischemic stroke patients admitted to our hospital. Of these, 94% were treated
      within 60 minutes from arrival. Performing angiography or perfusion imaging
      doubled the in-hospital delays. Patients with in-hospital stroke or arriving very
      soon from symptom onset had longer delays because there was no time to prepare
      for their arrival. CONCLUSIONS: With multiple concurrent strategies it is
      possible to cut the median in-hospital delay to 20 minutes. The key is to do as
      little as possible after the patient has arrived at the emergency room and as
      much as possible before that, while the patient is being transported.

PMID- 22622859
TI  - Lafora progressive myoclonus epilepsy: glycogen storage disease vs
      neurodegenerative disease.

PMID- 22622860
TI  - Teriflunomide added to interferon-beta in relapsing multiple sclerosis: a
      randomized phase II trial.
AB  - OBJECTIVE: To evaluate teriflunomide as add-on therapy to ongoing stable-dosed
      interferon-beta (IFNbeta) in patients with relapsing forms of multiple sclerosis
      (RMS). METHODS: A total of 118 patients with RMS were randomly assigned 1:1:1 to
      receive oral placebo or teriflunomide, 7 or 14 mg, once daily for 24 weeks; 86
      patients entered the 24-week extension. The primary objective was to evaluate
      safety; secondary objectives were to evaluate the effects of treatment on disease
      activity assessed by MRI and relapse rate. RESULTS: Teriflunomide was well
      tolerated with a low and similar incidence of treatment-emergent adverse events
      (TEAEs) across the 3 groups; TEAEs led to treatment discontinuation of 4.9%,
      8.1%, and 7.9% of patients in the placebo, 7-mg, and 14-mg groups, respectively.
      The number of gadolinium-enhancing T1 (T1-Gd) lesions was reduced in both
      teriflunomide groups, with relative risk reductions (RRRs) of 84.6% (p = 0.0005)
      and 82.8% (p < 0.0001) for 7 and 14 mg, respectively, compared with IFNbeta alone
      at 48 weeks. T1-Gd lesion volume was also reduced in the 7-mg group (RRR 72.1%, p
      = 0.1104) and 14-mg group (RRR 70.6%, p = 0.0154). A trend toward dose-dependent
      reduction in annualized relapse rate was also noted (RRRs 32.6% [p = 0.4355] and
      57.9% [p = 0.1005] for 7 and 14 mg, respectively). CONCLUSION: Teriflunomide as
      add-on therapy to IFNbeta had acceptable safety and tolerability and reduced MRI
      disease activity compared with IFNbeta alone. CLASSIFICATION OF EVIDENCE: This
      study provides Class II evidence that teriflunomide, 7 and 14 mg, added to
      IFNbeta, is safe. The T1-Gd lesion burden was significantly reduced with both
      teriflunomide doses.

PMID- 22622861
TI  - Door-to-needle times in acute ischemic stroke: how low can we go?

PMID- 22622862
TI  - Serum 25-hydroxyvitamin D and risk of breast cancer: results of a large
      population-based case-control study in Mexican women.
AB  - PURPOSE: Epidemiologic studies have suggested that higher levels of circulating
      vitamin D may reduce breast cancer risk, but no studies have investigated this
      association among women in developing countries, and very few studies have
      further investigated this association according to menopausal status. METHODS: A
      population-based case-control study in Mexico with 1,000 incident breast cancer
      cases aged 35-69 years, enrolled shortly after diagnosis (0-6 days) and frequency
      matched to 1,074 controls on age, region, and health care system, was used to
      assess the association between serum 25-hydroxyvitamin D [25(OH)D] levels with
      overall, pre- and postmenopausal breast cancer risk. 25(OH)D concentration was
      measured on a random sub-sample of women (573 cases and 639 matched controls)
      using a liquid chromatography/tandem mass spectrometry method. Odds ratios (ORs)
      and 95 % confidence intervals (CIs) were estimated from multivariable conditional
      logistic regression models. RESULTS: Serum 25(OH)D concentration (per 10 ng/mL
      increase) showed a strong inverse association with risk of breast cancer among
      all (p(trend) = 0.001), pre- (p(trend) = 0.006) and postmenopausal women
      (p(trend) = 0.0001). Compared with a predefined lower concentration of 25(OH)D
      (<20 ng/mL), higher levels (>30 ng/mL) were associated with lower overall (OR =
      0.53, 95 % CI: 0.28-1.00; p(trend) = 0.002), pre- (OR = 0.60, 95 % CI: 0.16-2.17;
      p(trend) = 0.07) and postmenopausal (OR = 0.37, 95 % CI: 0.16-0.82; p(trend) =
      0.004) breast cancer risk. CONCLUSIONS: The results of this large population
      based case-control study indicate an inverse association between circulating
      vitamin D levels and breast cancer risk among pre- and postmenopausal Mexican
      women.

PMID- 22622863
TI  - Diabetes mellitus as a risk factor for gastrointestinal cancers among
      postmenopausal women.
AB  - OBJECTIVES: While diabetes has been linked to several cancers in the
      gastrointestinal (GI) tract, findings have been mixed for sites other than
      colorectal and liver cancer. We used the Women's Health Initiative (WHI) data and
      conducted a comprehensive assessment of associations between diabetes and GI
      malignancy (esophagus, stomach, liver, biliary, pancreas, colon, and rectal).
      METHODS: A total of 145,765 postmenopausal women aged 50-79 enrolled in the WHI
      were followed for a mean 10.3 years. Cox proportional hazard regression models
      were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for
      the association between GI cancers and diagnosed diabetes, including its duration
      and treatment. RESULTS: Diabetes at enrollment was associated with increased risk
      of liver (HR = 2.97; 95 % CI, 1.66-5.32), pancreatic (HR = 1.62; 95 % CI, 1.15
      2.30), colon (HR = 1.38; 95 % CI, 1.14-1.66), and rectal (HR = 1.87, 95 % CI:
      1.22-2.85) cancer. Diabetes severity, assessed by duration or need for
      pharmacotherapy, appeared to have stronger links to risk of liver, pancreatic,
      and rectal cancer, but not colon cancer. There was no statistically significant
      association of diabetes with biliary, esophageal, and stomach cancers.
      CONCLUSION: Type 2 diabetes is associated with a significantly increased risk of
      cancers of the liver, pancreas, colon, and rectum in postmenopausal women. The
      suggestion that diabetes severity further increases these cancer risks requires
      future studies.

PMID- 22622864
TI  - Arsenic induces apoptosis in myoblasts through a reactive oxygen species-induced
      endoplasmic reticulum stress and mitochondrial dysfunction pathway.
AB  - A pool of myoblasts available for myogenesis is important for skeletal muscle
      size. The decreased number of skeletal muscle fibers could be due to the
      decreased myoblast proliferation or cytotoxicity. Identification of toxicants
      that regulate myoblast apoptosis is important in skeletal muscle development or
      regeneration. Here, we investigate the cytotoxic effect and its possible
      mechanisms of arsenic trioxide (As(2)O(3)) on myoblasts. C2C12 myoblasts
      underwent apoptosis in response to As(2)O(3) (1-10 MUM), accompanied by increased
      Bax/Bcl-2 ratio, decreased mitochondria membrane potential, increased cytochrome
      c release, increased caspase-3/-9 activity, and increased poly (ADP-ribose)
      polymerase (PARP) cleavage. Moreover, As(2)O(3) triggered the endoplasmic
      reticulum (ER) stress indentified through several key molecules of the unfolded
      protein response, including glucose-regulated protein (GRP)-78, GRP-94, PERK,
      eIF2alpha, ATF6, and caspase-12. Pretreatment with antioxidant N-acetylcysteine
      (NAC, 0.5 mM) dramatically suppressed the increases in reactive oxygen species
      (ROS), lipid peroxidation, ER stress, caspase cascade activity, and apoptosis in
      As(2)O(3) (10 MUM)-treated myoblasts. Furthermore, As(2)O(3) (10 MUM) effectively
      decreased the phosphorylation of Akt, which could be reversed by NAC. Over
      expression of constitutive activation of Akt (c.a. Akt) also significantly
      attenuated As(2)O(3)-induced myoblast apoptosis. Taken together, these results
      suggest that As(2)O(3) may exert its cytotoxicity on myoblasts by inducing
      apoptosis through a ROS-induced mitochondrial dysfunction, ER stress, and Akt
      inactivation signaling pathway.

PMID- 22622865
TI  - Regio- and stereoselective syntheses of piperidine derivatives via ruthenium
      catalyzed coupling of propargylic amides and allylic alcohols.
AB  - Intermolecular selective coupling of linear allylic alcohols and propargylic
      amides occurs in the presence of a catalytic amount of the cationic ruthenium
      complex [Cp*Ru(NCCH(3))(3)]PF(6) followed by condensation to generate six
      membered cyclic enamides or hemiaminal ethers with water as the only side
      product.

PMID- 22622866
TI  - Structural and biochemical characterization of native and recombinant single
      insulin-like growth factor-binding domain protein (SIBD-1) from the Central
      American hunting spider Cupiennius salei (Ctenidae).
AB  - Cupiennius salei single insulin-like growth factor binding domain protein (SIBD
      1) is an 8.6 kDa Cys-, Pro-, and Gly-rich protein, discovered in the hemocytes of
      the Central American hunting spider Cupiennius salei. SIBD-1 exhibits high
      sequence similarity to the N-terminal domain of the insulin-like growth factor
      binding protein superfamily and has been reported to play an important role in
      the spider's immune system. Here, the recombinant expression and the elucidation
      of the three-dimensional structure of recombinant SIBD-1 and the characterization
      of the sugar moiety at Thr2 of native SIBD-1 is described in detail.

PMID- 22622867
TI  - Cooperative effects at water-crystalline silica interfaces strengthen surface
      silanol hydrogen bonding. An ab initio molecular dynamics study.
AB  - Silica and silica based materials are widely used in chemistry and materials
      science due to their importance in many technological fields. The properties of
      these materials, which are crucial for their applications, are mainly determined
      by the presence of hydrogen bonding between surface silanols. Here, we present ab
      initio molecular dynamics simulations (AIMD) on different surfaces derived from
      the crystallographic alpha-quartz (100) and the alpha-cristobalite (001) and
      (101) faces, both free and at the interface with liquid water. The focus was on
      studying whether water adsorption can disrupt the H-bond pattern at the pristine
      free silica surface and how deep the perturbation due to the contact with the
      surface affects the structure of the water multilayer. Results highlight that the
      water phase is over structured at the interface with silica, as compared to water
      bulk. Furthermore, an apparent counterintuitive behavior has been observed for
      quartz (100) and cristobalite (001) surfaces: the interaction with water does not
      cleave the pre-existent H-bonds between the surface silanol groups. On the
      contrary, in several cases, it is observed that SiOH...OHSi H-bonds are even
      strengthened, as the result of a mutual cooperative H-donor/H-acceptor
      enhancement between silanols and water molecules, which may alter the adsorption
      capability of these silica surfaces.

PMID- 22622868
TI  - Association study of polymorphisms in the cyclooxygenase-2 gene and Alzheimer's
      disease risk in Chinese.
AB  - To determine if polymorphisms (-765G/C, -1195G/A and 8473T/C) of the
      cyclooxygenase-2 (COX-2) gene can be associated with Alzheimer disease (AD). The
      frequency of the polymorphisms was determined in 244 cases and 226 controls. The
      results revealed that the distributions of COX-2 -765G/C and 8473T/C
      polymorphisms were statistically not significant between AD cases and controls.
      The genotype distributions and allele frequencies of COX-2 -1195G/A polymorphism
      in the cases were statistically significantly different from the controls (P <
      0.05). The A/A distribution and A allele frequency were significantly lower in
      the AD group. COX-2 -1195AA carriers showed a one-third lower risk of developing
      AD as compared to those with -1195GG and GA genotypes (OR = 0.3, 95 % CI 0.194
      0.465, P = 0.000). This study suggested that -1195G/A polymorphism of the COX-2
      gene is associated with the risk of AD, and the A allele represents a protective
      factor in patients with AD.

PMID- 22622869
TI  - Chronic high-frequency stimulation therapy in hemiparkinsonian rhesus monkeys
      using an implanted human DBS system.
AB  - Deep brain stimulation (DBS) is routinely used in the treatment of Parkinson's
      disease, tremor disease, dystonia, and epilepsy. This study aims to establish a
      hemiparkinsonian monkey model and to investigate the effect of implanted human
      DBS system for the chronic alleviation of parkinsonian symptoms. Hemiparkinsonism
      was induced in four rhesus monkeys by unilateral infusion of 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine. DBS leads were implanted stereotaxically in the right
      subthalamic (STN) of the monkeys. Subcutaneous extension wires were used to
      connect the leads to the internal pulse generators (IPG) for stimulation in two
      of the monkeys (human DBS test group). Post-operative imaging studies confirmed
      optimal locations of lead contacts. One week later, the IPG was turned on to
      determine the optimal stimulating parameters, using apomorphine (APO)-induced
      rotation as a behavioral readout. Animal behavior was scored on a scale of 0-10
      over a 12-month period using the modified disability rating scale of
      hemiparkinsonian monkeys (DRSH). Parkinsonian symptoms in the group of monkeys
      with DBS improved dramatically (DRSH 3-4) compared to controls (DRSH 7-8). DBS
      leads were within the STN without intracranial hemorrhage, infection, or other
      serious complications. Histological examination showed cell necrosis and
      lymphocytic infiltration of the tissues around the lead and STN gliosis
      surrounding the lead contact. This study demonstrates that therapeutically
      effective human DBS systems can be established in relevant disease models in
      monkeys. Such combination of human DBS systems in hemiparkinsonian monkeys should
      be valuable in studying the mechanism of action and chronic consequences of DBS
      therapy in humans.

PMID- 22622871
TI  - Assisted tandem catalytic RCM-aromatization in the synthesis of pyrroles and
      furans.
AB  - An assisted tandem catalytic transformation of diallyl amines and diallyl ethers
      into N-aryl pyrroles and furans, respectively, is described. The sequence relies
      on ring closing metathesis followed by dehydrogenation of the initially formed
      dihydropyrroles and dihydrofurans. Both steps are Ru-catalyzed, but the sequence
      requires only one precatalyst, because conversion of the metathesis catalyst into
      the dehydrogenation catalyst is achieved in situ, triggered by the oxidant tert
      butyl hydroperoxide.

PMID- 22622870
TI  - A sleep continuity scale in Alzheimer's disease: validation and relationship with
      cognitive and functional deterioration.
AB  - Considering that disrupted sleep may be detrimental to daytime performance in
      people with dementia, we set out to construct a questionnaire able to identify
      sleep patterns potentially associated with clinical and functional disease
      variables in this population. Two subsets of items indicative of patterns of
      unstable sleep and of disordered rapid eye movement sleep (REM) were selected.
      The first included items investigating sleep continuity, with low sleep
      continuity markers considered indicative of high arousability; the second
      included items investigating the frequency and quality of dreams and the
      frequency of clinically identifiable REM sleep behaviour disorder episodes. The
      questionnaire was administered to 140 outpatients with a diagnosis of mild-to
      moderate Alzheimer's disease. The Mini-Mental State Examination (MMSE),
      Activities of Daily Living (ADL), Instrumental Activities of Daily Living,
      Neuropsychiatric Inventory and Clinical Dementia Rating (CDR) were administered
      to quantify cognitive, functional and behavioural impairment. A subscale
      comprising items investigating sleep discontinuity/fragmentation and showing high
      internal consistency was constructed and found to correlate significantly with
      variables considered indexes of cognitive and functional deterioration in AD
      (MMSE, ADL and CDR). Conversely, it did not prove possible to obtain a subscale
      of dysfunctional REM phenomena. The use of a rapidly and easily administered
      sleep scale, like the one we constructed, appears to be suitable for early
      identification and longitudinal monitoring of sleep disturbances in AD.

PMID- 22622872
TI  - Effects of an invasive plant transcend ecosystem boundaries through a dragonfly
      mediated trophic pathway.
AB  - Trophic interactions can strongly influence the structure and function of
      terrestrial and aquatic communities through top-down and bottom-up processes.
      Species with life stages in both terrestrial and aquatic systems may be
      particularly likely to link the effects of trophic interactions across ecosystem
      boundaries. Using experimental wetlands planted with purple loosestrife (Lythrum
      salicaria), we tested the degree to which the bottom-up effects of floral density
      of this invasive plant could trigger a chain of interactions, changing the
      behavior of terrestrial flying insect prey and predators and ultimately cascading
      through top-down interactions to alter lower trophic levels in the aquatic
      community. The results of our experiment support the linkage of terrestrial and
      aquatic food webs through this hypothesized pathway, with high loosestrife floral
      density treatments attracting high levels of visiting insect pollinators and
      predatory adult dragonflies. High floral densities were also associated with
      increased adult dragonfly oviposition and subsequently high larval dragonfly
      abundance in the aquatic community. Finally, high-flower treatments were coupled
      with changes in zooplankton species richness and shifts in the composition of
      zooplankton communities. Through changes in animal behavior and trophic
      interactions in terrestrial and aquatic systems, this work illustrates the broad
      and potentially cryptic effects of invasive species, and provides additional
      compelling motivation for ecologists to conduct investigations that cross
      traditional ecosystem boundaries.

PMID- 22622873
TI  - Context dependence in foraging behaviour of Achillea millefolium.
AB  - Context-dependent foraging behaviour is acknowledged and well documented for a
      diversity of animals and conditions. The contextual determinants of plant
      foraging behaviour, however, are poorly understood. Plant roots encounter patchy
      distributions of nutrients and soil fungi. Both of these features affect root
      form and function, but how they interact to affect foraging behaviour is unknown.
      We extend the use of the marginal value theorem to make predictions about the
      foraging behaviour of roots, and test our predictions by manipulating soil
      resource distribution and inoculation by soil fungi. We measured plant movement
      as both distance roots travelled and time taken to grow through nutrient patches
      of varied quality. To do this, we grew Achillea millefolium in the centers of
      modified pots with a high-nutrient patch and a low-nutrient patch on either side
      of the plant (heterogeneous) or patch-free conditions (homogeneous). Fungal
      inoculation, but not resource distribution, altered the time it took roots to
      reach nutrient patches. When in nutrient patches, root growth decreased relative
      to homogeneous soils. However, this change in foraging behaviour was not
      contingent upon patch quality or fungal inoculation. Root system breadth was
      larger in homogeneous than in heterogeneous soils, until measures were influenced
      by pot edges. Overall, we find that root foraging behaviour is modified by
      resource heterogeneity but not fungal inoculation. We find support for
      predictions of the marginal value theorem that organisms travel faster through
      low-quality than through high-quality environments, with the caveat that roots
      respond to nutrient patches per se rather than the quality of those patches.

PMID- 22622874
TI  - Interactions between nematodes and their microbial enemies in coastal sand dunes.
AB  - European foredunes are almost exclusively colonised by Ammophila arenaria, and
      both the natural succession and the die-out of this plant have been linked to
      populations of plant-parasitic nematodes (PPN). The overarching aim of this study
      was to investigate top-down control processes of PPN in these natural ecosystems
      through comparative analyses of the diversity and dynamics of PPN and their
      microbial enemies. Our specific aims were, first, to identify and quantify PPN
      microbial enemies in European sand dunes; second, to assess their life history
      traits, their spatial and temporal variation in these ecosystems, and third, to
      evaluate their control potential of PPN populations. This was done by seasonal
      sampling of a range of sites and making observations on both the nematode and the
      microbial enemy communities in rhizosphere sand. Nine different nematode
      microbial enemies belonging to different functional groups were detected in
      European sand dunes. Their high diversity in these low productivity ecosystems
      could both result from or lead to the lack of dominance of a particular nematode
      genus. The distribution of microbial enemies was spatially and temporally
      variable, both among and within sampling sites. Obligate parasites, either with
      low host-specificity or having the ability to form an environmentally resistant
      propagule, are favoured in these ecosystems and are more frequent and abundant
      than facultative parasites. Three microbial enemies correlated, either positively
      or negatively, with PPN population size: Catenaria spp., Hirsutella rhossiliensis
      and Pasteuria penetrans. Microbial-enemy supported links in the food-web may be
      involved in the control of PPN populations through indirect effects. The
      endospore-forming P. penetrans was the most successful top-down control agent,
      and was implicated in the direct control of Meloidogyne spp. and indirect
      facilitation of Pratylenchus spp. Overall, our findings suggest strong and
      diverse top-down control effects on the nematode community in these natural
      ecosystems.

PMID- 22622875
TI  - Reciprocal subsidies in ponds: does leaf input increase frog biomass export?
AB  - Reciprocal subsidies occur when ecosystems are paired, both importing and
      exporting resources to each other. The input of subsidies increases reciprocal
      subsidy export, but it is unclear how this changes with other important factors,
      such as ambient resources. We provide a conceptual framework for reciprocal
      subsidies and empirical data testing this framework using a pond-forest system in
      Missouri, USA. Our experiment used in situ pond mesocosms and three species of
      anurans: wood frogs, American toads, and southern leopard frogs. We predicted
      that increases in ambient resources (primary productivity) and detrital subsidy
      input (deciduous tree leaves) into pond mesocosms would increase reciprocal
      export (frog biomass) to the surrounding terrestrial ecosystem. In contrast, we
      found that increases in primary productivity consistently decreased frog biomass,
      except with leaf litter inputs. With leaf inputs, primary productivity did not
      affect the export of frogs, indicating that leaf detritus and associated
      microbial communities may be more important than algae for frog production. We
      found that subsidy inputs tended to increase reciprocal exports, and thus partial
      concordance with our conceptual framework.

PMID- 22622876
TI  - Benefits of photosynthesis for insects in galls.
AB  - Insect-induced plant galls are predominantly reputed to act as strong carbon
      sinks, although many types of galls contain chlorophyll and have the potential to
      photosynthesize. We investigated whether the photosynthetic capacity of bud galls
      induced by a Pteromalid wasp, Trichilogaster acaciaelongifoliae, in Acacia
      longifolia subsidises carbon budgets or provides O(2) to the larvae while
      concurrently consuming CO(2) in the dense gall tissue, thereby maintaining (O(2))
      and (CO(2)) within the range of larval tolerance. Low (O(2)) (<5 % v/v) were
      found within the internal tissues of galls, and these concentrations responded
      only marginally to light, suggesting that the photosynthetic activity within the
      gall is inconsequential in the provision of O(2) to the larvae. The metabolic
      response of larvae to reduced (O(2)) and elevated (CO(2)) indicated that larvae
      were tolerant of hypoxia/hypercarbia and also capable of reducing their
      respiratory rates to cope with hypercarbia. The low mortality of larvae in galls
      shaded with Al-foil for 20 days showed that photosynthesis was not vital for the
      survival of the larvae, although growth of shaded galls was substantially
      reduced. Gas exchange measurements confirmed that, while photosynthesis never
      fully compensated for the respiratory costs of galls, it contributed
      substantially to the maintenance and growth, especially of young galls, reducing
      their impact as carbon sinks on the host. We conclude that, although
      photosynthesis may contribute to O(2) provision, its main role is to reduce the
      dependence of the insect-induced gall on the host plant for photosynthates,
      thereby reducing intra-plant, inter-gall competition and enhancing the
      probability that each gall will reach maturity.

PMID- 22622877
TI  - Toward a preoperative planning tool for brain tumor resection therapies.
AB  - BACKGROUND: Neurosurgical procedures involving tumor resection require surgical
      planning such that the surgical path to the tumor is determined to minimize the
      impact on healthy tissue and brain function. This work demonstrates a predictive
      tool to aid neurosurgeons in planning tumor resection therapies by finding an
      optimal model-selected patient orientation that minimizes lateral brain shift in
      the field of view. Such orientations may facilitate tumor access and removal,
      possibly reduce the need for retraction, and could minimize the impact of brain
      shift on image-guided procedures. METHODS: In this study, preoperative magnetic
      resonance images were utilized in conjunction with pre- and post-resection laser
      range scans of the craniotomy and cortical surface to produce patient-specific
      finite element models of intraoperative shift for 6 cases. These cases were used
      to calibrate a model (i.e., provide general rules for the application of patient
      positioning parameters) as well as determine the current model-based framework
      predictive capabilities. Finally, an objective function is proposed that
      minimizes shift subject to patient position parameters. Patient positioning
      parameters were then optimized and compared to our neurosurgeon as a preliminary
      study. RESULTS: The proposed model-driven brain shift minimization objective
      function suggests an overall reduction of brain shift by 23 % over experiential
      methods. CONCLUSIONS: This work recasts surgical simulation from a trial-and
      error process to one where options are presented to the surgeon arising from an
      optimization of surgical goals. To our knowledge, this is the first realization
      of an evaluative tool for surgical planning that attempts to optimize surgical
      approach by means of shift minimization in this manner.

PMID- 22622883
TI  - Electromagnetic tracking for US-guided interventions: standardized assessment of
      a new compact field generator.
AB  - PURPOSE: One of the main challenges related to electromagnetic tracking in the
      clinical setting is a placement of the field generator (FG) that optimizes the
      reliability and accuracy of sensor localization. Recently, a new mobile FG for
      the NDI Aurora((r)) tracking system has been presented. This Compact FG is the
      first FG that can be attached directly to an ultrasound (US) probe. The purpose
      of this study was to assess the precision and accuracy of the Compact FG in the
      presence of nearby mounted US probes. MATERIALS AND METHODS: Six different US
      probes were mounted onto the Compact FG by means of a custom-designed mounting
      adapter. To assess precision and accuracy of the Compact FG, we employed a
      standardized assessment protocol. Utilizing a specifically manufactured plate, we
      measured positional data on three levels of distances from the FG as well as
      rotational data. RESULTS: While some probes had negligible influence on tracking
      accuracy two probes increased the mean distance error up to 1.5 mm compared with
      a reference measurement of 0.5 mm. The jitter error consistently stayed below 0.2
      mm in all cases. The mean relative error in orientation was found to be smaller
      than 3 degrees . CONCLUSION: Attachment of an US probe to the Compact FG does not
      have a critical influence on tracking accuracy in most cases. Clinical benefit of
      this promising mobile FG must be shown in future studies.

PMID- 22622884
TI  - Non-iterative partial view 3D ultrasound to CT registration in ultrasound-guided
      computer-assisted orthopedic surgery.
AB  - PURPOSE: In image-guided orthopedic surgery, rigid registration of intra
      operative ultrasound (US) to a pre-operative plan, developed using computed
      tomography (CT) scans, is an important step for providing real time surgical
      guidance. The ability to perform this registration accurately, automatically, and
      in real time is critical for enabling more effective image guidance and anatomic
      restoration in a number of orthopedic procedures. Several surface-based and
      intensity-based registration methods have been proposed before to align the US
      and CT data. Although relatively successful results were reported, both methods
      require accurate segmentation or localization of the bone surface in US data,
      which is a challenging task. Furthermore, typically, only partial views of the
      three-dimensional (3D) bone anatomy are visible in US data, and registration
      would only converge if a good estimation of the initial alignment between the US
      and CT datasets is known. METHODS: We propose a 3D rigid CT to US registration
      method based on the alignment of local phase bone image projections. The
      registration is achieved by transforming the local phase bone features,
      calculated using 3D Log-Gabor filters, to a projection space obtained using 3D
      Radon transform. Validation experiments show the capability of the method in
      registering partial view US volumes to full view CT volume. RESULTS: Feasibility
      experiments, carried out on a phantom and ten volunteer subjects, show an average
      surface registration, in the region where the US scans were acquired, of 0.42 and
      0.78  mm, respectively. CONCLUSIONS: The proposed US to CT registration method is
      fully automatic, non-iterative and requires no initial alignment between the two
      registering datasets.

PMID- 22622901
TI  - Altered rhythm of adrenal clock genes, StAR and serum corticosterone in VIP
      receptor 2-deficient mice.
AB  - The circadian time-keeping system consists of clocks in the suprachiasmatic
      nucleus (SCN) and in peripheral organs including an adrenal clock linked to the
      rhythmic corticosteroid production by regulating steroidogenic acute regulatory
      protein (StAR). Clock cells contain an autonomous molecular oscillator based on a
      group of clock genes and their protein products. Mice lacking the VPAC2 receptor
      display disrupted circadian rhythm of physiology and behaviour, and therefore, we
      using real-time RT-PCR quantified (1) the mRNAs for the clock genes Per1 and
      Bmal1 in the adrenal gland and SCN, (2) the adrenal Star mRNA and (3) the serum
      corticosterone concentration both during a light/dark (L/D) cycle and at constant
      darkness in wild type (WT) and VPAC2 receptor-deficient mice (VPAC2-KO). We also
      examined if PER1 and StAR were co-localised in the adrenal steroidogenic cells.
      Per1 and Bmal1 mRNA showed a 24-h rhythmic expression in the adrenal of WT mice
      under L/D and dark conditions. During a L/D cycle, the adrenal clock gene rhythm
      in VPAC2-KO mice was phase-advanced by approximately 6 h compared to WT mice and
      became arrhythmic in constant darkness. A significant 24-h rhythmic variation in
      the adrenal Star mRNA expression and circulating corticosterone concentration was
      similarly phase-advanced during the L/D cycle. The loss of adrenal clock gene
      rhythm in the VPAC2 receptor knockout mice after transfer into constant darkness
      was accompanied by disappearance of rhythmicity in Star mRNA expression and serum
      corticosterone concentration. Double immunohistochemistry showed that the PER1
      protein and StAR were co-localised in the same steroidogenic cells. Circulating
      corticosterone plays a role in the circadian timing system and the misaligned
      corticosterone rhythm in the VPAC2 receptor knockout mice could be involved in
      their abnormal rhythms of physiology.

PMID- 22622903
TI  - Intravesical onabotulinumtoxinA injections for refractory painful bladder
      syndrome.
AB  - BACKGROUND: Bladder pain associated with interstitial cystitis and painful
      bladder syndrome (IC/PBS) is frequently excruciating and intractable. The use of
      onabotulinumtoxinA (BoNT-A) for relief of this type of bladder pain has not been
      well described. OBJECTIVES: To evaluate the efficacy and safety of intravesical
      BoNT-A injection for treatment of IC/PBS refractory to conventional treatment.
      STUDY DESIGN: Prospective, non-randomized study. SETTING: A tertiary medical
      center in Taiwan. METHODS: Sixty-seven patients with characteristic IC/PBS were
      enrolled. Intravesical injection of 100U of BoNT-A immediately followed by
      cystoscopic hydrodistention under intravenous general anesthesia. Changes of the
      urodynamic parameters, O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI)
      and Interstitial Cystitis Problem Index (ICPI), visual analog score (VAS) for
      pain, functional bladder capacity, and global response assessment (GRA) were
      evaluated at baseline and 6 months after BoNT-A injection. Adverse events that
      occurred after this procedure were also assessed. RESULTS: Significant
      improvement was shown after intravesical injection of 100 U of BoNT-A. Baseline
      and 6 months after injection scores were: ICSI and ICPI (23.6 +/- 5.9 versus 15.2
      +/- 8.5, P = 0.000), VAS (5.3 +/- 2.2 versus 3.3 +/- 2.4, P = 0.000), functional
      bladder capacity (136 +/- 77.6 versus 180 +/- 78.2, P = 0.000) and GRA (0.3 +/-
      0.8 versus 1.4 +/- 1.0, P = 0.000). LIMITATIONS: This study lacks a placebo
      control group so the placebo effect cannot be eliminated. This study also does
      not provide information about the efficacy of this treatment after 6 months.
      CONCLUSION: Intravesical onabotulinumtoxinA injection appears to be a safe and
      effective therapeutic option for analgesia and increased bladder capacity for
      patients with IC/PBS. INSTITUTIONAL REVIEW: This study was approved by the
      Institutional Review Board of the Buddhist Tzu-chi General Hospital.

PMID- 22622902
TI  - Glucocorticoid receptor and myocyte enhancer factor 2 cooperate to regulate the
      expression of c-JUN in a neuronal context.
AB  - The glucocorticoid receptor (GR) and myocyte enhancer factor 2 (MEF2) are
      transcription factors involved in neuronal plasticity. c-JUN, a target gene of GR
      and MEF2, plays a role in regulating both synaptic strength and synapse number.
      The aim of this study was to investigate the nature of this dual regulation of c
      JUN by GR and MEF2 in a neuronal context. First, we showed that GR mediates the
      dexamethasone-induced suppression of c-JUN mRNA expression. Next, we observed
      that GR activation resulted in an increase in phosphorylation of MEF2, a post
      translational modification known to change MEF2 from a transcriptional enhancer
      to a repressor. In addition, we observed an enhanced binding of MEF2 to genomic
      sites directly upstream of the c-JUN gene upon GR activation. Finally, in primary
      hippocampal neuronal cultures, knockdown of MEF2 not only reduced c-JUN
      expression levels but abolished GR regulation of c-JUN expression. This suggests
      that MEF2 is necessary for GR regulation of c-JUN. In conclusion, for the first
      time, we show that activated GR requires MEF2 to regulate c-JUN. At the same
      time, GR influences MEF2 activity and DNA binding. These results give novel
      insight into the molecular interplay of GR and MEF2 in the control of genes
      important for neuronal plasticity.

PMID- 22622904
TI  - Cervical spinal cord stimulation: an analysis of 23 patients with long-term
      follow-up.
AB  - BACKGROUND: For more than 3 decades, spinal cord stimulation has successfully
      been employed to treat neuropathic pain. Cervical spinal cord stimulation,
      despite now being standard in many hospitals, has only rarely been subjected to a
      critical review within the literature. OBJECTIVES: The aim of this study was to
      determine the efficacy of cervical spinal cord stimulation (SCS) in a
      representative clinical sample. We also wanted to evaluate how factors such as
      stimulation parameters, unwanted paresthesia of the trunk and legs, and changes
      in paresthesia status due to head movement and how they affect SCS effectiveness.
      STUDY DESIGN: Retrospective study. SETTING: Academic university interdisciplinary
      pain center. METHODS: We reviewed the records of patients who had been treated at
      our institution with cervical neurostimulators from November 1, 2001 through
      October 31, 2011. Information regarding age, gender, diagnosis, age at time of
      implantation, duration of disease, lead position, hardware in use, revision
      operations, and stimulation parameters were recorded. In addition, a short
      telephone interview was conducted, which contained the following items: pain
      scores on the numeric analog scale (NAS) with and without stimulation, time
      intervals of stimulation, paresthesia coverage, changes in paresthesia coverage
      by head movements, unwanted paresthesia of the trunk and legs, treatment
      satisfaction, and medication intake. RESULTS: Twenty-three patients were treated.
      Eighteen patients proceeded to an implantable pulse generator (IPG) implant. In
      one patient, the system was removed after 4 years despite optimal function,
      because the patient was no longer experiencing pain. Average NAS pain scores were
      6.8 (range 5.5 - 10.0, standard deviation [SD] 1.7) without, and 2.8 (range 0 -
      7.5, SD 2.2) with neurostimulation. Fourteen revisions (5 due to lead
      dislocation, 5 due to lead breakage and 4 IPG revisions) were necessary in 9 of
      the 18 patients during a mean follow-up of 6.2 years. Most patients reported
      complete paresthesia coverage. Four patients reported unwanted paresthesia of the
      trunk or lower limb and 11 patients reported changes in paresthesia with head
      movements. In both instances, pain reduction was not affected. LIMITATIONS:
      Retrospective study. CONCLUSIONS: Cervical spinal cord stimulation appears to be
      effective in the treatment of neuropathic upper limb pain. Complications are not
      significantly more frequent than in SCS for lower limb pain. Changes in
      paresthesia with head movements and unwanted paresthesia did not affect the
      outcome.

PMID- 22622905
TI  - Clinical effectiveness of percutaneous adhesiolysis using Navicath for the
      management of chronic pain due to lumbosacral disc herniation.
AB  - BACKGROUND: Epidural steroid injection has been frequently performed to treat
      chronic pain due to lumbosacral disc herniation (L-HIVD). However, a considerable
      number of patients do not achieve pain relief using this method because
      perineural or epidural adhesions prevent the spread of injectate into the
      epidural space. Percutaneous adhesiolysis (PA) is thought to be a useful method
      because it can eliminate the deleterious effects of adhesion. OBJECTIVES: This
      study aimed to evaluate the effectiveness of PA in managing chronic pain due to L
      HIVD and the clinical and radiological predictive factors for the effectiveness
      of PA using NaviCath(r). STUDY DESIGN: Retrospective study SETTING: Spine
      hospital METHODS: From a group of patients diagnosed with L-HIVD, we selected the
      86 patients who underwent PA with NaviCath(r) who had experienced chronic lower
      back or leg pain for at least 3 months and had failed to respond to anti
      inflammatory medications or physical therapy of at least 1 month's duration and
      fluoroscopy guided transforaminal epidural injection. We recorded the Numeric
      Rating Scale for back pain (NRS back) and leg pain (NRS leg) and the Oswestry
      Disability Index (ODI) at pretreatment, 2 weeks, and 3 months after treatment.
      Clinical data and magnetic resonance imaging (MRI) findings were obtained to
      assess the possible predictive factors for PA efficacy. LIMITATIONS:
      Retrospective chart review without a control group. RESULTS: At 2 weeks after PA,
      significant improvement was observed in NRS back, NRS leg, and ODI compared with
      pretreatment. This improvement was maintained until 3 months after treatment.
      Among 86 patients, 61 (70.9%), 53 (61.6%) and 61 patients (70.9%) showed
      successful outcomes in NRS back, NRS leg, and ODI at 2 weeks, respectively. Among
      74 patients who were followed up at 3 months, 47 (63.5%), 44 patients (59.5%),
      and 50 patients (67.6%) showed successful results in NRS back, NRS leg, and ODI
      at 3 months, respectively. A significantly higher proportion of patients with a
      history of previous lumbar surgery showed unsuccessful results on NRS back, NRS
      leg, and ODI scores at 2 weeks and 3 months. Co-existence of spinal stenosis was
      associated with a significantly higher proportion of unsuccessful results in NRS
      back and ODI at 2 weeks and 3 months, as well as NRS leg at 3 months. Patients
      with spondylolisthesis also showed a significantly higher proportion of
      unsuccessful results in NRS and ODI at 2 weeks. CONCLUSION: PA with NaviCath(r)
      showed clinical effectiveness in the treatment of chronic pain due to L-HIVD that
      was not responsive to transforaminal epidural injection. Previous surgery and the
      presence of spinal stenosis or spondylolisthesis were poor prognostic predictors.
      This procedure may enable the physician to place the catheter tip and deliver
      medicine more precisely.

PMID- 22622906
TI  - Feasibility, safety and cement leakage in vertebroplasty of osteoporotic and
      malignant compression fractures using ultra-viscous cement and hydraulic delivery
      system.
AB  - BACKGROUND: The major complications arising from vertebroplasty or kyphoplasty
      are related to leakage of cement beyond the confines of the collapsed vertebral
      body. Traditionally, a liquid (low viscosity) cement is used in most
      vertebroplasty systems available on the market, coupled with mechanical injection
      devices or one mL syringes. OBJECTIVES: The purpose of this study is to evaluate
      the feasibility and safety, as well as study cement leakage patterns, in
      vertebroplasty performed for both osteoporotic and malignant vertebral
      compression fractures using ultraviscous cement injected by the hydraulic
      CONFIDENCE Vertebral Augmentation System. STUDY DESIGN: Retrospective evaluation
      of postoperative images. SETTING: Single center inpatient and outpatient
      population. METHODS: A retrospective evaluation of clinical charts and
      postoperative X-ray imaging was performed in 122 cases; a total of 214 levels
      were treated. The study group comprised a total of 163 levels of benign
      osteoporotic fractures and 51 levels of various malignant lesions. The degree of
      leakage, seen in postoperative films, was assessed at each treated level using a
      strict 4-point scale (none, mild, moderate, severe). RESULTS: For benign lesions,
      there was no leakage in 82 levels (50%), mild venous leakage in 38 levels (23%),
      moderate venous leakage in 4 levels (2%), mild disc leakage in 28 levels (17%),
      moderate disc leakage in 7 levels (4%), mild paravertebral leakage in 2 levels
      (1%), and moderate paravertebral leakage in 2 levels (1%). No severe leakage or
      epidural leakage were seen. For malignant lesions, there was no leakage in 25
      levels (49%), mild venous leakage in 12 levels (24%), moderate venous leakage in
      4 levels (8%), mild disc leakage in 7 levels (14%), moderate disc leakage in one
      level (2%), mild paravertebral leakage in one level (2%), and one level showed a
      mild epidural leakage (2%). LIMITATIONS: Retrospective study, single center.
      CONCLUSION: Percutaneous cement augmentation in osteoporotic and malignant
      compression fractures using a highly viscous cement that can be safely controlled
      and injected via a hydraulic system can be performed safely without significant
      complications. The leakage rate and patterns were similar in both benign and
      malignant compression fractures. The use of highly viscous cement may decrease
      the complication rate in malignant lesions that has been traditionally described
      to exhibit more cement leakage with low viscosity cement.

PMID- 22622907
TI  - Changes in bone mineral density in postmenopausal women treated with epidural
      steroid injections for lower back pain.
AB  - BACKGROUND: Therapy with corticosteroids often results in bone loss and
      corticosteroid-induced osteoporosis. In previous studies, bone mineral density
      (BMD) has been examined after administration of relatively high oral doses of
      corticosteroids. However, practitioners use comparatively lower doses of
      corticosteroids for epidural steroid injections (ESI). The interactions and
      relationships between BMD and ESI remain to be determined. OBJECTIVE: The aim of
      this study was to explore the relationship between BMD and ESI in postmenopausal
      women treated for lower back pain. STUDY DESIGN: This study was a retrospective
      evaluation. METHODS: We reviewed the medical records of postmenopausal women with
      lower back pain who were treated with or without ESI. BMD was measured before
      treatment and one year after treatment in the lumbar spine, femoral neck, and
      total femur. A total of 90 postmenopausal women were divided into 2 groups. Group
      1 patients received medications without ESI; Group 2 patients received ESI more
      than 4 times, with a cumulative administered triamcinolone dose of  > 120 mg.
      RESULTS: Decreased BMD was observed in patients treated with ESI. However, no
      significant difference was observed between or within the groups in terms of mean
      percentage change from baseline BMD. LIMITATIONS: First, this study is limited by
      the fact that it was retrospective. Second, our study did not consider the use of
      ESI with high-dose corticosteroids. Third, our study did not include any long
      term assessments of the effects of ESI on BMD. CONCLUSIONS: These data suggest
      that ESI using triamcinolone (over 200 mg) for a period of one year will have a
      negative effect on BMD in postmenopausal women treated for lower back pain.
      However, ESI therapy using a maximum cumulative triamcinolone dose of 200 mg in
      one year would be a safe treatment method with no significant impact on BMD.

PMID- 22622908
TI  - Radiofrequency neurolysis versus local nerve infiltration in 42 patients with
      refractory chronic inguinal neuralgia.
AB  - BACKGROUND: Chronic inguinal neuralgia involving ilioinguinal and iliohypogastric
      nerves is a frequent complication of surgical procedures involving a lower
      abdominal incision such as hernia repair, appendicitis surgery, or cesarean
      sections. Chronic inguinal neuralgia is a very painful condition and diagnosis
      can be challenging as it is an overlooked impairment. Existing specific
      treatments are inefficient and often fail. OBJECTIVE: The purposes of this study
      are to describe, evaluate, and compare ilioinguinal and iliohypogastric
      radiofrequency neurolysis (RFN) and local injection. STUDY DESIGN: Retrospective
      comparison cohort study from 2005 to 2011. SETTING: A single center, Academic
      Interventional Pain Management Unit METHODS: Forty-two patients suffering from
      chronic inguinal pain refractory to specific medication were included. A total of
      18 RFN procedures (14 patients) and 28 injections (28 patients) were performed.
      Pain was assessed in both groups using Visual Analog Scale (VAS) scores (0-10)
      measured immediately before and after the procedure and at one, 3, 6, 9, and 12
      months after the procedure. Mean duration of pain prior to the procedure and mean
      duration of pain relief were noted. Moreover, mean maximum early pain relief was
      assessed. All procedures were ambulatory under computed tomography (CT) guidance.
      Injections contained 1.5 mL of cortivazol and 3 mL of lidocaine-ropivacaine (30%
      70%). Radiofrequency neurolysis was performed using a Neurotherm RF Generator. In
      both cases, 22-gauge needles were used. After needle retrieval, control slices
      were taken and the patient was supervised for 30 minutes at the CT unit. RESULTS:
      The mean age in both groups was 48.7 years. Forty-two patients (97.6%) presented
      postsurgical inguinal pain, 62% of which occurred after hernia repair. All
      included patients had undergone previously unsuccessful pain therapies. Mean VAS
      scores were 7.72 in the RF group and 7.46 in the infiltration group. Maximum
      early pain relief did not statistically differ (77% in the RFN group and 81.5% in
      the injection group). Mean duration of pain relief was statistically significant
      (P = .005) in the RF group (12.5 months) compared to the infilitration group (1.6
      months). Mean VAS scores during the year following the procedure were all
      significantly in favor of radiofrequency neurolysis management. LIMITATIONS:
      Those inherent to small study samples and retrospective studies. CONCLUSION:
      Radiofrequency neurolysis appears to be significantly more effective than local
      nerve infiltrations. It is a safe and effective treatment for chronic inguinal
      pain. Local steroid injection along with local injection of anesthetics should be
      used as a confirmation of ilioinguinal neuropathy before performing
      radiofrequency neurolysis.

PMID- 22622909
TI  - Occipital nerve stimulation for chronic migraine: a randomized trial.
AB  - BACKGROUND: Chronic migraine (CM) and medication overuse headache (MOH) are
      disabling conditions that may be only partially managed with conservative
      treatments. Occipital nerve stimulation (ONS) is an innovative treatment for
      headache disorders. OBJECTIVES: To investigate the safety and efficacy of ONS for
      CM and MOH patients and to evaluate changes in disability, quality of life, and
      drug intake in implanted patients. STUDY DESIGN: Prospective, randomized cross
      over study. METHODS: Eligible patients who responded to a stimulation trial
      underwent device implantation and were randomized to "Stimulation On" and
      "Stimulation Off" arms. Patients crossed over after one month, or when their
      headaches worsened. Stimulation was then switched On for all patients. Disability
      as measured by the Migraine Disability Assessment (MIDAS), quality of life (SF
      36), and drug intake (patient's diary) were assessed over a one-year follow-up.
      RESULTS: Thirty-four patients (76% women, 34% men, mean age: 46 +/- 11 years)
      were enrolled; 30 were randomized and 29 completed the study. Headache intensity
      and frequency were significantly lower in the On arm than in the Off arm (p  <
      0.05) and decreased from the baseline to each follow-up visit in all patients
      with Stimulation On (median MIDAS A and B scores: baseline = 70 and 8; one-year
      follow-up = 14 and 5, p  < 0.001). Quality of life significantly improved (p  <
      0.05) during the study. Triptans and nonsteroidal anti-inflammatory drug use fell
      dramatically from the baseline (20 and 25.5 doses/month) to each follow-up visit
      (3 and 2 doses/month at one year, p  < 0.001). A total of 5 adverse events
      occurred: 2 infections and 3 lead migrations. LIMITATIONS: Single-centre study,
      relatively small number of patients, absence of a control group. CONCLUSIONS:
      According to the results obtained, ONS appears to be a safe and effective
      treatment for  carefully selected CM and MOH patients.

PMID- 22622910
TI  - Skin biopsy in complex regional pain syndrome: case series and literature review.
AB  - BACKGROUND: Accumulating experimental and clinical evidence supports the
      hypothesis that complex regional pain syndrome type I (CRPS-I) may be a small
      fiber neuropathy. OBJECTIVES: To evaluate the use of commercially available
      standard biopsy methods to detect intradermal axon pathology in CRPS-I, and to
      ascertain if these structural changes can explain quantitative sensory testing
      (QST) findings in CRPS-I. STUDY DESIGN: Retrospective review of charts and
      laboratory data. SETTING: Outpatient clinic METHODS: Skin biopsies from 43
      patients with CRPS-I were stained with PGP 9.5, and epidermal nerve fiber
      density, sweat gland nerve fiber density and morphological abnormalities were
      evaluated. Thirty-five patients had quantitative sensory testing. RESULTS:
      Alterations in skin innervation were seen in approximately 20% of CRPS-I patients
      with commercial processing. There were no patient characteristics, including
      duration of disease, that predicted a decreased epidermal nerve fiber density
      (ENFD). There was no consistent relationship between QST changes and ENFD
      measured by standard commercial skin biopsy evaluation procedures. LIMITATIONS:
      Commercial processing of tissue does not utilize stereologic quantitative
      analysis of nerve fiber density. Biopsy material is utilized from a proximal and
      distal source only, and differences in denervation of a partial nerve territory
      may be missed. The functional attributes of small fibers cannot be assessed.
      CONCLUSIONS: The negative results indicate that CRPS-I may be associated with
      changes in the ultramicroscopic small fiber structure that cannot be visualized
      with commercially available techniques. Alternatively, functional rather than
      structural alterations of small fibers or pathological changes at a more proximal
      site such as the spinal cord or brain may be responsible for the syndrome.

PMID- 22622911
TI  - Caudal epidural injections in the management of chronic low back pain: a
      systematic appraisal of the literature.
AB  - BACKGROUND: Epidural injections with local anesthetics and steroids are one of
      the most commonly used interventions in managing chronic low back pain and lower
      extremity pain of various causes. However, despite their extensive use, debate
      continues on their effectiveness due to the lack of well-designed, randomized,
      controlled studies to determine the effectiveness of epidural injections in
      general, and caudal epidural injections in particular. STUDY DESIGN: A systematic
      review of caudal epidural injections with or without steroids in managing chronic
      pain secondary to lumbar disc herniation or radiculitis, post lumbar laminectomy
      syndrome, spinal stenosis, and discogenic pain without disc herniation or
      radiculitis. OBJECTIVE: To evaluate the effect of caudal epidural injections with
      or without steroids in managing various types of chronic low back pain with or
      without lower extremity pain emanating as a result of disc herniation or
      radiculitis, post lumbar laminectomy syndrome, spinal stenosis, and chronic
      discogenic pain. METHODS: The available literature on caudal epidural injections
      with or without steroids in managing various types of chronic low back pain with
      or without lower extremity pain was reviewed. The quality assessment and clinical
      relevance criteria utilized were the Cochrane Musculoskeletal Review Group
      criteria as utilized for interventional techniques for randomized trials and the
      criteria developed by the Newcastle-Ottawa Scale criteria for fluoroscopic
      observational studies. The level of evidence was classified as good, fair, or
      poor based on the quality of evidence developed by the U.S. Preventive Services
      Task Force (USPSTF). Data sources included relevant literature identified through
      searches of PubMed and EMBASE from 1966 to December 2011, and manual searches of
      the bibliographies of known primary and review articles. OUTCOME MEASURES: The
      primary outcome measure was pain relief (short-term relief = up to 6 months and
      long-term > 6 months). Secondary outcome measures of improvement in functional
      status, psychological status, return to work, and reduction in opioid intake were
      utilized. RESULTS: For this systematic review, 73 studies were identified. Of
      these, 51 were excluded and a total of 16 studies met inclusion criteria for
      methodological quality assessment with 11 randomized trials and 5 non-randomized
      studies.  For lumbar disc herniation, the evidence is good for short- and long
      term relief of chronic pain secondary to disc herniation or radiculitis with
      local anesthetic and steroids and fair relief with local anesthetic only. In
      managing chronic axial or discogenic pain, spinal stenosis, and post surgery
      syndrome, the indicated evidence is fair. LIMITATIONS: The limitations of this
      study include the paucity of literature, specifically for chronic pain without
      disc herniation. CONCLUSION: There was good evidence for short- and long-term
      relief of chronic pain secondary to disc herniation or radiculitis with local
      anesthetic and steroids and fair relief with local anesthetic only. Further, this
      systematic review also provided indicated evidence of fair for caudal epidural
      injections in managing chronic axial or discogenic pain, spinal stenosis, and
      post surgery syndrome.

PMID- 22622912
TI  - Effectiveness of therapeutic lumbar transforaminal epidural steroid injections in
      managing lumbar spinal pain.
AB  - BACKGROUND: Among the multiple interventions used in managing chronic spinal
      pain, lumbar epidural injections have been used extensively to treat lumbar
      radicular pain. Among caudal, interlaminar, and transforaminal, transforaminal
      epidural injections have gained rapid and widespread acceptance for the treatment
      of lumbar and lower extremity pain. The potential advantages of transforaminal
      over interlaminar and caudal, include targeted delivery of a steroid to the site
      of pathology, presumably onto an inflamed nerve root. However, there are only a
      few well-designed, randomized, controlled studies on the effectiveness of steroid
      injections. Consequently, multiple systematic reviews with diverse opinions have
      been published. STUDY DESIGN: A systematic review of therapeutic transforaminal
      epidural injection therapy for low back and lower extremity pain. OBJECTIVE: To
      evaluate the effect of therapeutic transforaminal lumbar epidural steroid
      injections in managing low back and lower extremity pain. METHODS: The available
      literature on lumbar transforaminal epidural injections in managing chronic low
      back and lower extremity pain was reviewed. The quality assessment and clinical
      relevance criteria utilized were the Cochrane Musculoskeletal Review Group
      criteria as utilized for interventional techniques for randomized trials and by
      the Newcastle-Ottawa Scale criteria for observational studies. Data sources
      included relevant literature identified through searches of PubMed and EMBASE
      from 1966 to December 2011, and manual searches of the bibliographies of known
      primary and review articles. The level of evidence was classified as good, fair,
      or poor based on the quality of evidence developed by the U.S. Preventive
      Services Task Force (USPSTF). OUTCOME MEASURES: The primary outcome measure was
      pain relief (short-term relief = up to 6 months and long-term  > 6 months).
      Secondary outcome measures were improvement in functional status, psychological
      status, return to work, and reduction in opioid intake. RESULTS: For this
      systematic review, 70 studies were identified. Of these, 43 studies were excluded
      and a total of 27 studies met inclusion criteria for methodological quality
      assessment with 15 randomized trials (with 2 duplicate publications) and 10 non
      randomized studies. For lumbar disc herniation, the evidence is good for
      transforaminal epidural with local anesthetic and steroids, whereas it was fair
      for local anesthetics alone and the ability of transforaminal epidural injections
      to prevent surgery. For spinal stenosis, the available evidence is fair for local
      anesthetic and steroids. The evidence for axial low back pain and post lumbar
      surgery syndrome is poor, inadequate, limited, or unavailable. LIMITATIONS: The
      limitations of this systematic review include the paucity of literature.
      CONCLUSION: In summary, the evidence is good for radiculitis secondary to disc
      herniation with local anesthetics and steroids and fair with local anesthetic
      only; it is fair for radiculitis secondary to spinal stenosis with local
      anesthetic and steroids; and limited for axial pain and post surgery syndrome
      using local anesthetic with or without steroids.

PMID- 22622913
TI  - A systematic evaluation of the therapeutic effectiveness of sacroiliac joint
      interventions.
AB  - BACKGROUND: The contribution of the sacroiliac joint to low back and lower
      extremity pain has been a subject of debate with extensive research. It is
      generally accepted that approximately 10% to 25% of patients with persistent low
      back pain may have pain arising from the sacroiliac joints. In spite of this,
      there are currently no definite conservative, interventional, or surgical
      management options for managing sacroiliac joint pain. In addition, there
      continue to be significant variations in the application of various techniques as
      well as a paucity of literature. STUDY DESIGN: A systematic review of therapeutic
      sacroiliac joint interventions. OBJECTIVE: To evaluate the accuracy of
      therapeutic sacroiliac joint interventions. METHODS: The available literature on
      therapeutic sacroiliac joint interventions in managing chronic low back and lower
      extremity pain was reviewed. The quality assessment and clinical relevance
      criteria utilized were the Cochrane Musculoskeletal Review Group criteria for
      randomized trials of interventional techniques and the criteria developed by the
      Newcastle-Ottawa Scale for observational studies. The level of evidence was
      classified as good, fair, or poor based on the quality of evidence developed by
      the U.S. Preventive Services Task Force (USPSTF).  Data sources included relevant
      literature published from 1966 through December 2011 that was identified through
      searches of PubMed and EMBASE, and manual searches of the bibliographies of known
      primary and review articles. OUTCOME MEASURES: The primary outcome measure was
      pain relief (short-term relief = up to 6 months and long-term  > 6 months).
      Secondary outcome measures were improvement in functional status, psychological
      status, return to work, and reduction in opioid intake. RESULTS: For this
      systematic review, 56 studies were considered for inclusion. Of these, 45 studies
      were excluded and a total of 11 studies met inclusion criteria for methodological
      quality assessment with 6 randomized trials and 5 non-randomized studies. The
      evidence for cooled radiofrequency neurotomy in managing sacroiliac joint pain is
      fair.The evidence for effectiveness of intraarticular steroid injections is
      poor.The evidence for periarticular injections of local anesthetic and steroid or
      botulinum toxin is poor. The evidence for effectiveness of conventional
      radiofrequency neurotomy is poor.The evidence for pulsed radiofrequency is poor.
      LIMITATIONS: The limitations of this systematic review include a paucity of
      literature on therapeutic interventions, variations in technique, and variable
      diagnostic standards for sacroiliac joint pain. CONCLUSIONS: The evidence was
      fair in favor of cooled radiofrequency neurotomy and poor for short-term and long
      term relief from intraarticular steroid injections, periarticular injections with
      steroids or botulin toxin, pulsed radiofrequency, and conventional radiofrequency
      neurotomy.

PMID- 22622914
TI  - Effectiveness of thermal annular procedures in treating discogenic low back pain.
AB  - BACKGROUND: Persistent low back pain refractory to conservative treatment is a
      common problem that leads to widespread impairment, resulting in significant
      costs to society. The intervertebral disc is a major source of persistent low
      back pain. Technologies developed to treat this problem, including various
      surgical instrumentation and fusion techniques, have not reliably provided
      satisfactory results in terms of either pain relief or increased function. 
      Thermal annular procedures (TAPs) were first developed in the late 1990s in an
      attempt to treat discogenic pain. The hope was that they would provide greater
      value than fusion in terms of efficacy, morbidity, and cost. Three technologies
      have been developed to apply heat to the annulus: intradiscal electrothermal
      therapy (IDET), discTRODE, and biacuplasty. Since nerve ingrowth and tissue
      regeneration in the annulus is felt to be the source of pain in discogenic low
      back pain, when describing the 3 above techniques we use the term "thermal
      annular procedures" rather than "thermal intradiscal procedures." We have
      specifically excluded studies treating the nucleus. TAPs have been the subject of
      significant controversy. Multiple reviews have been conducted resulting in
      varying conclusions. STUDY DESIGN: A systematic review of TAPs for the treatment
      of discogenic low back pain. OBJECTIVE: To evaluate the effectiveness of TAPs in
      treating discogenic low back pain and to assess complications associated with
      those procedures. METHODS: The available literature on TAPs in treating
      discogenic low back pain was reviewed. The quality assessment and clinical
      relevance criteria utilized were the Cochrane Musculoskeletal Review Group
      criteria for interventional techniques for randomized trials, and the criteria
      developed by the Newcastle-Ottawa Scale criteria for observational studies. The
      level of evidence was classified as good, fair, or poor based on the quality of
      evidence developed by the U.S. Preventive Services Task Force. Data sources
      included relevant literature identified through searches of PubMed and EMBASE
      from 1966 through December 2011, and manual searches of the bibliographies of
      known primary and review articles. OUTCOME MEASURES: The primary outcome measure
      was pain relief of at least 6 months. Secondary outcome measures were
      improvements in functional status. RESULTS: For this systematic review, 43
      studies were identified. Of these, 3 randomized controlled trials and one
      observational study met the inclusion criteria. Using current criteria for
      successful outcomes, the evidence is fair for IDET and poor for discTRODE and
      biacuplasty procedures regarding whether they are effective in relieving
      discogenic low back pain. Since 2 randomized controlled trials are in progress on
      that procedure, assessment of biacuplasty may change upon publication of those
      studies. LIMITATIONS: The limitations of this systematic review include the
      paucity of literature and non-availability of 2 randomized trials which are in
      progress for biacuplasty. CONCLUSION: In summary, the evidence is fair for IDET
      and poor for discTRODE and biacuplasty is being evaluated in 2 ongoing randomized
      controlled trials.

PMID- 22622915
TI  - A systematic evaluation of prevalence and diagnostic accuracy of sacroiliac joint
      interventions.
AB  - BACKGROUND: The contributions of the sacroiliac joint to low back and lower
      extremity pain have been a subject of considerable debate and research. It is
      generally accepted that 10% to 25% of patients with persistent mechanical low
      back pain below L5 have pain secondary to sacroiliac joint pathology. However, no
      single historical, physical exam, or radiological feature can definitively
      establish a diagnosis of sacroiliac joint pain. Based on present knowledge, a
      proper diagnosis can only be made using controlled diagnostic blocks. The
      diagnosis and treatment of sacroiliac joint pain continue to be characterized by
      wide variability and a paucity of the literature. OBJECTIVE: To evaluate the
      accuracy of diagnostic sacroiliac joint interventions. STUDY DESIGN: A systematic
      review of diagnostic sacroiliac joint interventions. METHODS: Methodological
      quality assessment of included studies was performed using Quality Appraisal of
      Reliability Studies (QAREL). Only diagnostic accuracy studies meeting at least
      50% of the designated inclusion criteria were utilized for analysis. Studies
      scoring less than 50% are presented descriptively and analyzed critically.  The
      level of evidence was classified as good, fair, or poor based on the quality of
      evidence developed by the United States Preventive Services Task Force (USPSTF).
      Data sources included relevant literature identified through searches of PubMed
      and EMBASE from 1966 to December 2011, and manual searches of the bibliographies
      of known primary and review articles. OUTCOME MEASURES: In this evaluation we
      utilized controlled local anesthetic blocks using at least 50% pain relief as the
      reference standard. RESULTS: The evidence is good for the diagnosis of sacroiliac
      joint pain utilizing controlled comparative local anesthetic blocks. The
      prevalence of sacroiliac joint pain is estimated to range between 10% and 62%
      based on the setting; however, the majority of analyzed studies suggest a point
      prevalence of around 25%, with a false-positive rate for uncontrolled blocks of
      approximately 20%. The evidence for provocative testing to diagnose sacroiliac
      joint pain was fair. The evidence for the diagnostic accuracy of imaging is
      limited. LIMITATIONS: The limitations of this systematic review include a paucity
      of literature, variations in technique, and variable criterion standards for the
      diagnosis of sacroiliac joint pain. CONCLUSIONS: Based on this systematic review,
      the evidence for the diagnostic accuracy of sacroiliac joint injections is good,
      the evidence for provocation maneuvers is fair, and evidence for imaging is
      limited.

PMID- 22622916
TI  - Autologous adipose tissue-derived stem cells induce persistent bone-like tissue
      in osteonecrotic femoral heads: a molecular mechanism.

PMID- 22622918
TI  - Posterior epidural contrast injection via posterolateral transforaminal approach.

PMID- 22622919
TI  - CT-guided transforaminal epidural injections with local anesthetic, steroid, and
      tramadol.

PMID- 22622921
TI  - Muscle rigidity associated with pregabalin.

PMID- 22622922
TI  - Caudal epidural injections for the treatment of tarlov cysts: suggestions for the
      better results.

PMID- 22622924
TI  - The soluble dietary fiber inulin can influence the bioaccessibility of enniatins.
AB  - Enniatins (ENs) are bioactive compounds produced by the secondary metabolism of
      several Fusarium strains and are known to have various biological activities,
      such as acting as enzyme inhibitors, antifungal antibacterial agents, and
      immunomodulatory substances. This study investigated the bioaccessibility of the
      ENs in wheat crispy breads produced with three different inulin concentrations
      (1, 5 and 10%). The mean bioaccessibility data of the four ENs (A, A(1), B and
      B(1)) ranged from 68.67% to 84.67 in the experiments carried out without inulin,
      whereas the data ranged from 51.00 to 74.00% in the experiments carried out with
      the wheat crispy bread produced with 5 and 10% of the inulin.

PMID- 22622946
TI  - High-resolution in vivo imaging of microglia using a versatile nongenetically
      encoded marker.

PMID- 22622947
TI  - Eicosanoids mediate cellular immune response and phenoloxidase reaction to viral
      infection in adult Pimpla turionellae.
AB  - Nodulation is the predominant insect cellular immune response to microbial
      infections. We posed the hypothesis that parasitoid insects in their adulthood
      express melanotic nodulation reactions to viral challenge and that eicosanoids
      mediate nodulation reactions and phenoloxidase (PO) activation in response to
      viral challenge. To test this idea, we injected Pimpla turionellae adults with
      indomethacin, a nonsteroidal anti-inflammatory drug, immediately prior to
      intrahemocoelic injection of Bovine herpes simplex virus-1 (BHSV-1). Treating
      newly emerged adults of P. turionellae with BHSV-1 induced nodulation reactions,
      and decreased PO activity at high viral doses. Relative to vehicle-treated
      controls, indomethacin-treated adults produced significantly reduced numbers of
      nodules following viral infection (down from approximately 21 nodules per adult
      to less than six nodules per adult). In addition to injection treatments,
      increasing dietary indomethacin dosages (from 0.01% to 0.1%) were associated with
      decreasing nodulation (by six-fold) and PO (by about three-fold) reactions to
      BHSV-1 injection. Wasp adults orally fed with the lowest dietary indomethacin
      concentration (0.001%) expressed significantly increased PO activity (1.45
      unit/min/mg protein) while nodulation reaction was not affected in response to
      viral challenge compared to control adults. We infer from these findings that
      cyclooxygenase (COX) products, at least prostaglandins, mediate nodulation
      response and PO action to viral infection in adults of these highly specialized
      insects.

PMID- 22622948
TI  - Efficacy of pharmacotherapy in bipolar disorder: a report by the WPA section on
      pharmacopsychiatry.
AB  - The current statement is a systematic review of the available data concerning the
      efficacy of medication treatment of bipolar disorder (BP). A systematic MEDLINE
      search was made concerning the treatment of BP (RCTs) with the names of treatment
      options as keywords. The search was updated on 10 March 2012. The literature
      suggests that lithium, first and second generation antipsychotics and valproate
      and carbamazepine are efficacious in the treatment of acute mania. Quetiapine and
      the olanzapine-fluoxetine combination are also efficacious for treating bipolar
      depression. Antidepressants should only be used in combination with an antimanic
      agent, because they can induce switching to mania/hypomania/mixed states/rapid
      cycling when utilized as monotherapy. Lithium, olanzapine, quetiapine and
      aripiprazole are efficacious during the maintenance phase. Lamotrigine is
      efficacious in the prevention of depression, and it remains to be clarified
      whether it is also efficacious for mania. There is some evidence on the efficacy
      of psychosocial interventions as an adjunctive treatment to medication.
      Electroconvulsive therapy is an option for refractory patients. In acute manic
      patients who are partial responders to lithium/valproate/carbamazepine, adding an
      antipsychotic is a reasonable choice. The combination with best data in acute
      bipolar depression is lithium plus lamotrigine. Patients stabilized on
      combination treatment might do worse if shifted to monotherapy during
      maintenance, and patients could benefit with add-on treatment with olanzapine,
      valproate, an antidepressant, or lamotrigine, depending on the index acute phase.
      A variety of treatment options for BP are available today, but still unmet needs
      are huge. Combination therapy may improve the treatment outcome but it also
      carries more side-effect burden. Further research is necessary as well as the
      development of better guidelines and algorithms for the step-by-step rational
      treatment.

PMID- 22622949
TI  - 18-fluoro-deoxy-glucose positron emission tomography with computed tomography
      based gross tumor volume estimation and validation with magnetic resonance
      imaging for locally advanced cervical cancers.
AB  - PURPOSE: Anatomy and morphology-based imaging is routinely used for radiotherapy
      purpose to deliver precision treatment. There is an interest in using information
      from functional imaging for conformal radiation therapy planning. These
      functional imaging techniques need to be validated rigorously before their
      routine use. We attempted to evaluate and validate the use of 18-fluoro-deoxy
      glucose positron emission tomography with computed tomography (18FDG PET-CT) on
      primary tumor of the cervical carcinoma, with an aim of arriving at a cutoff
      maximum standardized uptake value (SUVmax) at which the tumor volume correlates
      best with magnetic resonance imaging (MRI). This observational study was a part
      of an ethics committee-approved study evaluating pretreatment MRI and FDG PET-CT.
      MATERIALS AND METHODS: Patients' biopsy-proven cervical carcinomas (stages IIB
      and IIIB) were included in this study and underwent pretreatment MRI and FDG PET
      CT as per institutional protocol. Volumes of the disease at the cervix on the MR
      image were calculated. Volumes at the FDG PET-CT scan at different percentages of
      SUVmax were auto contoured. Volume at MRI was correlated with each different
      percentage cutoff of the SUVmax. RESULTS: Data of 74 patients were available for
      the study. The mean (SD) SUVmax of the primary tumor was 15.7 (7.0). The mean MRI
      volume correlates significantly (P < 0.001) with 30% and 35% of SUVmax values
      with good correlation according to the Pearson bivariate correlation (r = 0.79
      each). The mean difference between MRI and PET volumes was least with 30% SUVmax.
      CONCLUSIONS: 18FDG PET-CT SUV-based primary tumor volume estimation at 30% to 35%
      of SUVmax values correlates significantly with the criterion standard MR volumes
      for primary cervical tumor with squamous histology in our population.

PMID- 22622950
TI  - Management and prognosis of clear cell borderline ovarian tumor.
AB  - BACKGROUND: The clear cell borderline ovarian tumor (CCBOT) of the ovary is a
      rare tumor accounting for less than 1% of BOT. Fewer than 25 cases have been
      reported in the literature (including details on clinical management and
      outcomes). The aim of this study was to determine the prognosis of a series of
      CCBOTs collected in 2 reference centers. PATIENTS AND METHODS: This was a
      retrospective review of patients with CCBOT treated or referred to our
      institutions. A centralized histological review by a reference pathologist and
      data on the clinical characteristics, management, and outcomes of patients were
      required for inclusion. RESULTS: Twelve patients were identified between 2000 and
      2010. The median age of patients was 68 years (range, 36-83 years). Two had been
      treated conservatively and 9 radically (data unknown in 1). The tumor was
      unilateral in 11 cases. All patients had stage I disease. All cases were CCBOT
      with an adenofibromatous pattern. Stromal microinvasion or intraepithelial
      carcinoma was histologically associated in 2 and 3 cases, respectively. Four of
      the 12 patients had synchronous endometrial disorders (but no endometrioid
      carcinoma). No cases were histologically associated with endometriosis. Four
      patients were lost to follow-up. Among 8 other patients, after a median period of
      28 months (range, 2-129 months), no recurrence had occurred (1 patient had died
      of another disease). CONCLUSION: Clear cell borderline ovarian tumor carries a
      good prognosis. All tumors are stage I; therefore, surgical staging is not
      necessary in most of the cases. Conservative treatment could be proposed to young
      patients, but uterine curettage would then be required in cases of uterine
      preservation.

PMID- 22622951
TI  - Variant lineages of human papillomavirus type 18 in Northeast China populations
      characterized by sequence analysis of E6, E7, and L1 regions.
AB  - INTRODUCTION: In cervical cancer, human papillomavirus (HPV) 18 is predominantly
      related to adenocarcinomas. Variant lineages of HPV type 16 have been well
      characterized, whereas the knowledge about HPV 18 variants is limited in
      Northeast China. METHODS: To identify prevalent and novel HPV 18 variants in
      Northeast China, the E6, E7, and L1 genes of HPV 18 from patients with cervical
      lesion were amplified and sequenced, and intratypic variants were analyzed by
      comparing to the known phylogenetic branches. RESULTS: The HPV-18 E6 variants of
      our studied strains belong to 2 main branches: Asian-American (AA) variants in
      81.5% and European (E) variants in 18.5%. Strains with variations of C287G,
      T482C, and C519A in E6 and C751T in E7 were novel variants. All the L1 genes of
      the analyzed HPV 18 strains had 4 C-G transversions at nucleotide positions of
      5701, 6460, 6625, and 6842 and one G-A transition at position 5503. Moreover,
      strains with L1 nucleotide variations of A5920T, A6431T, and G6987A leading to
      amino acid substitutions of A164V, Q334P/H, and D520N are novel variants.
      CONCLUSIONS: Based on the E6 gene, the prevalent HPV 18 in Northeast China was AA
      and E variants. Besides some common variations reported before, some new
      variations in the E6, E7, and L1 genes were found. Data about the novel
      variations found in the L1 gene of HPV 18 variants may be helpful to design the
      diagnostic reagents and vaccine for naturally infected HPV 18 in Northeast China.

PMID- 22622952
TI  - A prospective single-center study of sentinel lymph node detection in cervical
      carcinoma: is there a place in clinical practice?
AB  - OBJECTIVE: To establish the accuracy of sentinel lymph node (SLN) detection in
      early cervical cancer. MATERIALS AND METHODS: Sentinel lymph node detection was
      performed prospectively over a 6-year period in 86 women undergoing surgery for
      cervical carcinoma by the combined method (Tc-99m and methylene blue dye).
      Further ultrastaging was performed on a subgroup of 26 patients who had benign
      SLNs on initial routine histological examination. RESULTS: The SLN was detected
      in 84 (97.7%) of 86 women by the combined method. Blue dye uptake was not seen in
      8 women (90.7%). Sentinel lymph nodes were detected bilaterally in 63 women
      (73.3%), and the external iliac region was the most common anatomic location
      (48.8%). The median SLN count was 3 nodes (range, 1-7). Of the 84 women with
      sentinel node detection, 65 also underwent bilateral pelvic lymph node
      dissection, and in none of these cases was a benign SLN associated with a
      malignant non-SLN (100% negative predictive value). The median non-SLN count for
      all patients was 19 nodes (range, 8-35). Eighteen patients underwent removal of
      the SLN without bilateral pelvic lymph node dissection. Nine women (10.5%) had
      positive lymph nodes on final histology. One patient had bulky pelvic nodes on
      preoperative imaging and underwent removal of the negative bulky malignant lymph
      nodes and a benign SLN on the contralateral side. This latter case confirms the
      unreliability of the SLN method with bulky nodes. The remaining 8 patients had
      positive SLNs with negative nonsentinel lymph nodes. Fifty-nine SLNs from 26
      patients, which were benign on initial routine histology, underwent ultrastaging,
      but no further disease was identified. Four patients (5%) relapsed after a median
      follow-up of 28 months (range, 8-80 months). CONCLUSION: Sentinel lymph node
      detection is an accurate and safe method in the assessment of nodal status in
      early cervical carcinoma.

PMID- 22622954
TI  - Transversus abdominis plane block for analgesia after Cesarean delivery: a
      systematic review and meta-analysis.
AB  - PURPOSE: To assess the efficacy of transversus abdominis plane (TAP) block in
      improving analgesia following Cesarean delivery (CD). SOURCE: We searched
      MEDLINE, CENTRAL, EMBASE, and CINAHL for randomized controlled trials that
      assessed the efficacy of TAP block following CD and reported on postoperative
      pain scores and/or opioid consumption. Studies were combined according to the use
      or non-use of intrathecal morphine (ITM). Another analysis was performed for
      studies comparing TAP block with ITM. PRINCIPAL FINDINGS: Nine studies were
      included. Transversus abdominis plane block significantly reduced opioid
      consumption (mg morphine equivalents) after Cesarean delivery at six hours (mean
      difference [MD] -10.18; 95% confidence interval [CI] -13.03 to -7.34), at 12 hr
      (MD -13.83; 95% CI -22.77 to -4.89), and at 24 hr (MD -20.23; 95% CI -33.69 to 
      6.77). The TAP block also reduced pain scores for up to 12 hr and nausea in
      patients who did not receive ITM. When added to ITM, TAP block produced a small
      reduction in pain scores on movement in the first six hours (MD -0.82, 95% CI 
      1.52 to -0.11). When compared with ITM, pain scores on movement and opioid
      consumption at 24 hr were lower (MD 0.98; 95% CI 0.06 to 1.91 and MD 8.42 mg; 95%
      CI 1.74 to 15.10, respectively), and time to first rescue analgesic was longer
      with ITM (8 hr vs 4 hr), although opioid-related side effects were more common.
      CONCLUSION: Transversus abdominis plane block significantly improved
      postoperative analgesia in women undergoing CD who did not receive ITM but showed
      no improvement in those who received ITM. Intrathecal morphine was associated
      with improved analgesia compared with TAP block alone at the expense of an
      increased incidence of side effects.

PMID- 22622955
TI  - Enzyme-triggered model self-assembly in surfactant-cyclodextrin systems.
AB  - We present here a host-guest approach to construct enzyme-triggered assembly
      systems on the basis of surfactant-cyclodextrin complexes and alpha-amylase. We
      realized enzyme-responsive model self-assembly systems including monolayers,
      micelles, and vesicles. The host-guest approach is expected to be extended to
      more complicated assembly systems with widespread applications.

PMID- 22622953
TI  - Variations in target gene expression and pathway profiles in the mouse
      hippocampus following treatment with different effective compounds for ischemia
      reperfusion injury.
AB  - In order to elucidate the overlapping and diverse pharmacological protective
      mechanisms of different Chinese medicinal compounds, we investigated the
      alteration of gene expression and activation of signaling pathways in the mouse
      hippocampus after treatment of cerebral ischemia-reperfusion injury with various
      compounds. A microarray including 16,463 genes was used to identify
      differentially expressed genes among six treatment groups: baicalin (BA),
      jasminoidin (JA), cholic acid (CA), concha margaritiferausta (CM), sham, and
      vehicle. The US Food and Drug Administration (FDA) ArrayTrack system and Kyoto
      Encyclopedia of Genes and Genomes (KEGG) database were used to screen
      significantly altered genes and pathways (P < 0.05, fold change >1.5). Vehicle
      treatment alone resulted in alteration of 726 genes (283 upregulated, 443
      downregulated) compared to the sham treatment group. BA, JA, and CA treatments,
      but not CM treatment, were effective in reducing infarct volume compared with
      vehicle treatment (P < 0.05). Compared with the CM group, a total of 167 (73
      upregulated, 94 downregulated), 379 (211 upregulated, 168 downregulated), and 181
      (76 upregulated, 105 downregulated) altered genes were found in the BA, JA, and
      CA groups, respectively. The numbers of overlapping genes between the BA and JA,
      BA and CA, and JA and CA groups were 28 (16 upregulated, 12 downregulated), 14 (4
      upregulated, 10 downregulated), and 31 (8 upregulated, 23 downregulated),
      respectively. Three overlapping genes were identified among the BA, JA, and CA
      treatment groups: Il1rap, Gnb5, and Wdr38. Based on KEGG pathway analysis, two,
      seven, and four pathways were significantly activated in the BA, JA, and CA
      groups, respectively, when compared to the CM group. The ATP-binding cassette
      (ABC) transporters general pathway was activated by BA and JA treatment, and the
      mitogen-activated protein kinase (MAPK) signaling pathway was activated by JA and
      CA treatment. Alteration of IL-1 and Hspa1a expression was found by real time
      reverse transcription polymerase chain reaction, confirming the results of the
      microarray analysis. Our data demonstrated that polytypic profiles of 167-379
      altered genes exist in the mouse hippocampus treated with different compounds
      known to be therapeutically effective in cerebral ischemia-reperfusion injury,
      and we were able to identify overlapping genes and pathways among these groups.
      Therefore, these different compounds may function through both overlapping and
      distinct pharmacological mechanisms to exert their therapeutic action.

PMID- 22622956
TI  - Glucose transporter-1 (GLUT1) deficiency syndrome: diagnosis and treatment in
      late childhood.
AB  - BACKGROUND: Typical cases of glucose transporter-1 deficiency syndrome (GLUT1-DS)
      present with early-onset epilepsy. We report symptoms, diagnostic results, and
      effects of therapy in two patients diagnosed with GLUT1-DS at the age of 10 and
      15 years, respectively. PATIENTS: Patient 1: After four cerebral seizures in the
      first 2 years of life the patient was seizure-free but showed a complex movement
      disorder, expressive speech disorder, and mental retardation. Ratio of
      cerebrospinal fluid (CSF) to blood glucose was 0.41 (reference range 0.65 +/-
      0.1), molecular genetic testing confirmed GLUT1 deficiency with the novel
      pathogenic mutation c.1377dupC (p.Phe460LeufsX3) in the SLC2A1 gene. Following 9
      months of ketogenic diet started at the age of 10 years, there was distinct
      improvement of speech and movement disorder. Patient 2 showed pharmacorefractive
      epilepsy, mental retardation, and a mild movement disorder. At the age of 15
      years, extensive intake of food with high fat content was observed. Ratio of CSF
      to blood glucose was 0.41 (reference range 0.65 +/- 0.1). The pathogenic mutation
      c.634C>T (p.Arg212Cys) was found in the SLC2A1 gene. CONCLUSION: Self-induced
      high-fat diet can be a hint toward GLUT1-DS. Ketogenic diet can be beneficial
      even when started in late childhood, although it may take several months to
      achieve a positive effect.

PMID- 22622957
TI  - Antituberculosis drug research: a critical overview.
AB  - The increasing drug resistance of Mycobacterium tuberculosis to the currently
      used drugs and HIV coinfection has caused alarm in the international scientific
      community. Subsequently, there is an urgent need for the development of new drug
      molecules with newer targets and with an alternative mechanism of action. Since
      the last 50 years, the same long-duration, multidrug treatment plan is being
      followed for the treatment of tuberculosis. The objective of this review article
      is to critically analyze the antitubercular potential of various classes of
      compounds (quinoline, diamine, quinolone, fluoroquinolone, quinone,
      nitroimidazole, terpenoid, isonicotinyl, oxazolidinone, pyrimidine, and purine),
      their possibility to be a future drug candidate, and latest information on the
      clinical status of some novel antitubercular compounds. Compounds such as
      moxifloxacin, PA824, and TMC207 are well tolerated and there is no adverse effect
      shown by them. Moxifloxacin and gatifloxacin shows cross-resistance to the
      currently used drugs while no cross-resistance observed in case of TMC207 and
      PA824. Some compounds like OPC67683 and PA824 are bactericidal in nature.

PMID- 22622958
TI  - Serotypes and genetic profiles of Bordetella pertussis strains isolated in the
      city of Sao Paulo, 2006-2008.
AB  - OBJECTIVE: Knowledge of Bordetella pertussis circulating in Latin America is
      limited. Therefore, the goal of this study was to use pulsed-field gel
      electrophoresis and serotyping to characterize B. pertussis strains isolated in
      the city of Sao Paulo, Brazil. METHODS: This study, conducted between 2006 and
      2008, analyzed 652 nasopharyngeal swabs from suspected pertussis cases and
      contacts, collected from 37 sentinel hospitals in Sao Paulo. Randomized samples
      of 91 (70%) strains of B. pertussis were subtyped by pulsed-field gel
      electrophoresis and serotyping. RESULTS: Ninety-seven percent of strains from Sao
      Paulo were serotyped as Fim3. Fourteen pulsed-field gel electrophoresis profiles
      were identified; the most prevalent (57%) is also the most prevalent in the USA.
      CONCLUSIONS: These data, in conjunction with surveillance activities, may impact
      strategies regarding prevention and control of pertussis in the region, providing
      useful information for introduction of new vaccination strategies and reduction
      of risk of transmission to infants less than 6 months of age.

PMID- 22622959
TI  - GSAFold: a new application of GSA to protein structure prediction.
AB  - The folding process defines three-dimensional protein structures from their amino
      acid chains. A protein's structure determines its activity and properties; thus
      knowing such conformation on an atomic level is essential for both basic and
      applied studies of protein function and dynamics. However, the acquisition of
      such structures by experimental methods is slow and expensive, and current
      computational methods mostly depend on previously known structures to determine
      new ones. Here we present a new software called GSAFold that applies the
      generalized simulated annealing (GSA) algorithm on ab initio protein structure
      prediction. The GSA is a stochastic search algorithm employed in energy
      minimization and used in global optimization problems, especially those that
      depend on long-range interactions, such as gravity models and conformation
      optimization of small molecules. This new implementation applies, for the first
      time in ab initio protein structure prediction, an analytical inverse for the
      Visitation function of GSA. It also employs the broadly used NAMD Molecular
      Dynamics package to carry out energy calculations, allowing the user to select
      different force fields and parameterizations. Moreover, the software also allows
      the execution of several simulations simultaneously. Applications that depend on
      protein structures include rational drug design and structure-based protein
      function prediction. Applying GSAFold in a test peptide, it was possible to
      predict the structure of mastoparan-X to a root mean square deviation of 3.00 A.

PMID- 22622961
TI  - Structure and reactivity of small particles: from clusters to aerosols.

PMID- 22622960
TI  - Random fractional ultrapulsed CO2 resurfacing of photodamaged facial skin: long
      term evaluation.
AB  - Although numerous papers have recently been published on ablative fractional
      resurfacing, there is a lack of information in literature on very long-term
      results. The aim of this retrospective study is to evaluate the efficacy, adverse
      side effects, and long-term results of a random fractional ultrapulsed CO2 laser
      on a large population with photodamaged facial skin. Three hundred twelve
      patients with facial photodamaged skin were enrolled and underwent a single full
      face treatment. Six aspects of photodamaged skin were recorded using a 5 point
      scale at 3, 6, and 24 months after the treatment. The results were compared with
      a non-parametric statistical test, the Wilcoxon's exact test. Three hundred one
      patients completed the study. All analyzed features showed a significant
      statistical improvement 3 months after the procedure. Three months later all
      features, except for pigmentations, once again showed a significant statistical
      improvement. Results after 24 months were similar to those assessed 18 months
      before. No long-term or other serious complications were observed. From the
      significant number of patients analyzed, long-term results demonstrate not only
      how fractional ultrapulsed CO2 resurfacing can achieve good results on
      photodamaged facial skin but also how these results can be considered stable 2
      years after the procedure.

PMID- 22622963
TI  - Retraction. Development of a neural network for glucose concentration prevision
      in patients affected by type 1 diabetes.

PMID- 22622962
TI  - Study design, rationale, and baseline characteristics: evaluation of fenofibric
      acid on carotid intima-media thickness in patients with type IIb dyslipidemia
      with residual risk in addition to atorvastatin therapy (FIRST) trial.
AB  - PURPOSE: Elevated triglycerides (TG) and low high-density lipoprotein cholesterol
      (HDL-C) levels contribute to cardiovascular disease risk and can be effectively
      treated with fenofibric acid. A trial is under way to evaluate the effect of once
      daily fenofibric acid or placebo on carotid intima-media thickness (CIMT)
      progression in patients with controlled low-density lipoprotein cholesterol (LDL
      C) levels achieved through atorvastatin treatment, but with high TG and low HDL-C
      levels. METHODS: In this multicenter, double-blind study, 682 patients were
      randomized to once-daily delayed-release capsules of choline fenofibrate 135 mg
      (fenofibric acid [Trilipix((r)); Abbott, North Chicago, IL]) or placebo plus
      atorvastatin treatment after a 2- to 10-week diet and atorvastatin run-in period.
      Key inclusion criteria included age >=45 years; posterior-wall common CIMT >=0.7
      mm on at least one side at baseline; fasting results of TG >=150 mg/dL, and HDL-C
      <=45 mg/dL for men or HDL-C <=55 mg/dL for women at screening while receiving
      atorvastatin; controlled LDL-C; and known coronary heart disease (CHD) or a CHD
      risk equivalent. The primary efficacy variable is the rate of change from
      baseline through week 104 in the mean posterior-wall intima-media thickness of
      the common carotid arteries (composite value of left and right sides).
      CONCLUSIONS: This trial is the first to examine the effect of fenofibric acid on
      CIMT and the first CIMT trial to select patients with controlled LDL-C and
      elevated TG and low HDL-C as inclusion criteria. Also, this trial will
      prospectively evaluate the effect of treatment on LDL particles and address
      shortcomings of previous CIMT trials.

PMID- 22622964
TI  - Calculation of the release of total organic matter and total mineral using the
      hydrodynamic equations applied to palm oil mill effluent treatment by cascaded
      anaerobic ponds.
AB  - Anaerobic treatment processes to remove organic matter from palm oil mill
      effluent (POME) have been used widely in Malaysia. Still the amounts of total
      organic and total mineral released from POME that may cause degradation of the
      receiving environment need to be verified. This paper proposes the use of the
      hydrodynamic equations to estimate performance of the cascaded anaerobic ponds
      (CAP) and to calculate amounts of total organic matter and total mineral released
      from POME. The CAP efficiencies to remove biochemical oxygen demands, chemical
      oxygen demands, total solids and volatile solids (VS) as high as 94.5, 93.6, 96.3
      and 98.2 %, respectively, are estimated. The amounts of total organic matter and
      total mineral as high as 538 kg VS/day and 895 kg FS/day, respectively, released
      from POME to the receiving water are calculated. The implication of the proposed
      hydrodynamic equations contributes to more versatile environmental assessment
      techniques, sometimes replacing laboratory analysis.

PMID- 22622966
TI  - Three-dimensional extracellular matrix-mediated neural stem cell differentiation
      in a microfluidic device.
AB  - Here, we report a unique method to quantify the effects of in vivo-like
      extracellular matrix (ECM) for guiding differentiation of neural stem cells
      (NSCs) in three-dimensional (3D) microenvironments using quantitative real-time
      polymerase chain reaction (qRT-PCR). We successfully monitored and quantified
      differentiation of NSCs in small volume ECMs and found that differentiation of
      NSCs, especially those differentiating towards neuronal and oligodendrocytic
      lineages, is significantly enhanced by 3D microenvironments reconstituted in the
      microfluidic channels.

PMID- 22622965
TI  - Impact of lap-band size on weight loss: does gender matter?
AB  - BACKGROUND: Laparoscopic adjustable gastric band (LAGB) has gone through major
      design modifications to improve clinical endpoints and reduce complications.
      Little is known, however, about the effects of LAGB size on clinical outcomes, or
      whether outcomes differ based on gender. We set out to examine the impact of band
      size on surgical weight loss, reoperations, comorbidity resolution, and compare
      outcomes within gender. METHODS: We reviewed our prospectively collected
      longitudinal bariatric database between 2008 and 2010, and compared patients with
      BMI 35-50 kg/m(2) who had undergone LAGB with the LAP-BAND(r) APS to those who
      had the larger APL. Those patients with initial BMI > 50 kg/m(2) were excluded to
      reduce any possible selection bias which favors larger band use in such subjects.
      RESULTS: Three hundred ninety-four patients met our inclusion criteria; 230 (58
      %) in the APS group and 164 (42 %) in the APL group. Female patients in APS group
      experienced significantly higher percentage excess body weight loss at 6 months,
      1 year, and 2 years in comparison to female patients in APL group (p < 0.001 for
      all time points). In contrast, a reverse pattern was observed for male patients.
      No significant differences were observed between the groups regarding frequency
      of band adjustments, complications, or comorbidity resolution. CONCLUSIONS: Male
      patients might benefit from APL bands, in contrast to female patients who appear
      to experience superior weight loss with the smaller APS bands. This study
      provides the first set of evidence to facilitate surgical decision making for
      band size selection and highlights differences between genders.

PMID- 22622967
TI  - The effects of substituents and solvents on the ground-state pi-electronic
      structure and electronic absorption spectra of a series of model merocyanine dyes
      and their theoretical interpretation.
AB  - Two series of new merocyanine dyes have been synthesised and the dependence of
      their electronic structure on substituents and solvents has been studied by NMR
      spectroscopy, by using both the NMR (13)C chemical shifts between adjacent C
      atoms in the polymethine chain and the (3)J(H,H) coupling constants for trans
      vicinal protons. The widely used valence bond (VB) model based on two
      contributing structures cannot account theoretically for the observed alternating
      pi-electron density in the polymethine chain. In addition, the prediction of zero
      pi-bond order alternation (or zero-bond length alternation) by this model is also
      incorrect. However, the results are consistent with the predictions of a
      qualitative VB model which considers the resonance of a positive charge
      throughout the whole polymethine chain. Based on this model and the Franck-Condon
      principle the effect of substituents and solvents on the fine structure of the
      electronic spectra of these dyes can be explained as vibronic transitions from
      the vibrational state v = 0 to v', where v is the vibrational quantum number of
      the totally symmetric C=C valence vibration of the polymethine chain in the
      electronic ground state and v' is that in the electronic excited state. In
      contrast, neither the effects of substituents or solvents on the electronic
      structure of merocyanines and their electronic spectra can be accounted for by
      the simple two state VB model.

PMID- 22622969
TI  - Low-frequency meandering piezoelectric vibration energy harvester.
AB  - The design, fabrication, and characterization of a novel low-frequency meandering
      piezoelectric vibration energy harvester is presented. The energy harvester is
      designed for sensor node applications where the node targets a width-to-length
      aspect ratio close to 1:1 while simultaneously achieving a low resonant
      frequency. The measured power output and normalized power density are 118 MUW and
      5.02 MUW/mm(3)/g(2), respectively, when excited by an acceleration magnitude of
      0.2 g at 49.7 Hz. The energy harvester consists of a laser-machined meandering
      PZT bimorph. Two methods, strain-matched electrode (SME) and strain-matched
      polarization (SMP), are utilized to mitigate the voltage cancellation caused by
      having both positive and negative strains in the piezoelectric layer during
      operation at the meander's first resonant frequency. We have performed finite
      element analysis and experimentally demonstrated a prototype harvester with a
      footprint of 27 x 23 mm and a height of 6.5 mm including the tip mass. The device
      achieves a low resonant frequency while maintaining a form factor suitable for
      sensor node applications. The meandering design enables energy harvesters to
      harvest energy from vibration sources with frequencies less than 100 Hz within a
      compact footprint.

PMID- 22622970
TI  - Self-amplified magnetoelectric properties in a dumbbell-shaped
      magnetostrictive/piezoelectric composite.
AB  - We report magnetoelectric (ME) properties in a dumbbell-shaped metallic glass
      alloy/Pb(Zr(x)Ti(1-x))O(3) laminated composite, yielding a magnetic field
      amplification resulting from magnetic flux concentration effects of the dumbbell
      shaped design. Compared with the traditional rectangular structures, the modified
      geometry results in an effective improvement in the ME coefficient, a significant
      decrease in the required dc magnetic bias field, and an enhancement in magnetic
      field sensitivity.

PMID- 22622971
TI  - Ferroelectrically active acoustic wave propagation.
AB  - The ferroelectrically active acoustic wave equation including electrostriction
      effects is derived from nonlinear constitutive equations of stress and electric
      displacement for ferroelectric materials exhibiting significant electrostrictive
      strain. Electrically controllable acoustic wave propagation is predicted by
      solving the equation as a function of various acoustic variables, e.g., wave
      excitation, polarization, dc bias, etc. As examples, the elastic, piezoelectric,
      and ferroelectric acoustic waves and the electromechanical coupling factors are
      computed as a function of wave propagation in the [100]-[010] plane of BaTiO3
      under thickness excitation mode.

PMID- 22622972
TI  - Performance analysis and receiver architectures of DCF77 radio-controlled clocks.
AB  - DCF77 is a longwave radio transmitter located in Germany. Atomic clocks generate
      a 77.5-kHz carrier which is amplitude- and phase-modulated to broadcast the
      official time. The signal is used by industrial and consumer radio-controlled
      clocks. DCF77 faces competition from the Global Positioning System (GPS) which
      provides higher accuracy time. Still, DCF77 and other longwave time services
      worldwide remain popular because they allow indoor reception at lower cost, lower
      power, and sufficient accuracy. Indoor longwave reception is challenged by signal
      attenuation and electromagnetic interference from an increasing number of
      devices, particularly switched-mode power supplies. This paper introduces new
      receiver architectures and compares them with existing detectors and time
      decoders. Simulations and analytical calculations characterize the performance in
      terms of bit error rate and decoding probability, depending on input noise and
      narrowband interference. The most promising detector with maximum-likelihood time
      decoder displays the time in less than 60 s after powerup and at a noise level of
      E(b)/N(0) = 2.7 dB, an improvement of 20 dB over previous receivers. A field
      programmable gate array-based demonstration receiver built for the purposes of
      this paper confirms the capabilities of these new algorithms. The findings of
      this paper enable future high-performance DCF77 receivers and further study of
      indoor longwave reception.

PMID- 22622973
TI  - Real-time ultrasound simulation using the GPU.
AB  - Ultrasound simulators can be used for training ultrasound image acquisition and
      interpretation. In such simulators, synthetic ultrasound images must be generated
      in real time. Anatomy can be modeled by computed tomography (CT). Shadows can be
      calculated by combining reflection coefficients and depth dependent, exponential
      attenuation. To include speckle, a pre-calculated texture map is typically added.
      Dynamic objects must be simulated separately. We propose to increase the speckle
      realism and allow for dynamic objects by using a physical model of the underlying
      scattering process. The model is based on convolution of the point spread
      function (PSF) of the ultrasound scanner with a scatterer distribution. The
      challenge is that the typical field-of-view contains millions of scatterers which
      must be selected by a virtual probe from an even larger body of scatterers. The
      main idea of this paper is to select and sample scatterers in parallel on the
      graphic processing unit (GPU). The method was used to image a cyst phantom and a
      movable needle. Speckle images were produced in real time (more than 10 frames
      per second) on a standard GPU. The ultrasound images were visually similar to
      images calculated by a reference method.

PMID- 22622968
TI  - The Lewy body in Parkinson's disease and related neurodegenerative disorders.
AB  - The histopathological hallmark of Parkinson's disease (PD) is the presence of
      fibrillar aggregates referred to as Lewy bodies (LBs), in which alpha-synuclein
      is a major constituent. Pale bodies, the precursors of LBs, may serve the
      material for that LBs continue to expand. LBs consist of a heterogeneous mixture
      of more than 90 molecules, including PD-linked gene products (alpha-synuclein, DJ
      1, LRRK2, parkin, and PINK-1), mitochondria-related proteins, and molecules
      implicated in the ubiquitin-proteasome system, autophagy, and aggresome
      formation. LB formation has been considered to be a marker for neuronal
      degeneration because neuronal loss is found in the predilection sites for LBs.
      However, recent studies have indicated that nonfibrillar alpha-synuclein is
      cytotoxic and that fibrillar aggregates of alpha-synuclein (LBs and pale bodies)
      may represent a cytoprotective mechanism in PD.

PMID- 22622974
TI  - Quantitative ultrasonic characterization of diffuse scatterers in the presence of
      structures that produce coherent echoes.
AB  - Quantitative ultrasound (QUS) techniques that parameterize the backscattered
      power spectrum have demonstrated significant promise for ultrasonic tissue
      characterization. Some QUS parameters, such as the effective scatterer diameter
      (ESD), require the assumption that the examined medium contains uniform diffuse
      scatterers. Structures that invalidate this assumption can significantly affect
      the estimated QUS parameters and decrease performance when classifying disease.
      In this work, a method was developed to reduce the effects of echoes that
      invalidate the assumption of diffuse scattering. To accomplish this task,
      backscattered signal sections containing non-diffuse echoes were identified and
      removed from the QUS analysis. Parameters estimated from the generalized spectrum
      (GS) and the Rayleigh SNR parameter were compared for detecting data blocks with
      non-diffuse echoes. Simulations and experiments were used to evaluate the
      effectiveness of the method. Experiments consisted of estimating QUS parameters
      from spontaneous fibroadenomas in rats and from beef liver samples. Results
      indicated that the method was able to significantly reduce or eliminate the
      effects of nondiffuse echoes that might exist in the backscattered signal. For
      example, the average reduction in the relative standard deviation of ESD
      estimates from simulation, rat fibroadenomas, and beef liver samples were 13%,
      30%, and 51%, respectively. The Rayleigh SNR parameter performed best at
      detecting nondiffuse echoes for the purpose of removing and reducing ESD bias and
      variance. The method provides a means to improve the diagnostic capabilities of
      QUS techniques by allowing separate analysis of diffuse and non-diffuse
      scatterers.

PMID- 22622975
TI  - Optimal sound speed estimation using modified nonlinear anisotropic diffusion to
      improve spatial resolution in ultrasound imaging.
AB  - In ultrasound exams of obese patients and the breast, the spatial and contrast
      resolutions of ultrasound images are severely deteriorated when a constant sound
      speed corresponding to soft tissue is used in receive dynamic beamformation. This
      degradation is due to the defocusing of the ultrasound beam because of the
      disparity in sound speed between soft tissue and fatty layers. To minimize the
      degradation, this paper proposes a new method of estimating an optimal sound
      speed that can be used to achieve the best beamforming performance in a region of
      interest (ROI). The proposed method employs a new focusing quality factor (FQF)
      as an indicator of how well the focusing is conducted with a given sound speed.
      The FQF is closely associated with the degree of edge conspicuity, which can be
      obtained using the proposed modified nonlinear anisotropic diffusion (MNAD)
      technique. To calculate FQF, ultrasound images are formed with different sound
      speeds ranging from 1400 to 1600 m/s and, subsequently, the ROI is chosen. In the
      ROI, the degrees of edge conspicuity (i.e., FQF) are calculated. The sound speed
      can be considered an optimal one for the ROI if it is used to construct the image
      that provides the maximum FQF. The performances of the proposed method were
      evaluated through simulation and in vitro experiments with a tissue-mimicking
      phantom. The performance was also compared with that of the conventional image
      based method employed in a commercial ultrasound imaging system. The experimental
      results demonstrated that the proposed method is capable of estimating an optimal
      sound speed with an error of 10 m/s regardless of whether strong targets are
      included in the ROI or not. On the other hand, the conventional image-based
      method generated an estimation error of 60 m/s maximally in the case in which
      there were no strong targets in ROI. This indicates that the proposed method is a
      useful tool to improve ultrasound image quality for clinical applications,
      especially for ultrasound exams of obese patients and the breast.

PMID- 22622976
TI  - A reliability study of light refractive tomography utilized for noninvasive
      measurement of ultrasound pressure fields.
AB  - Light refractive tomography is an optical measurement technique that is able to
      provide absolute sound pressure values in specified volumes. Because of the
      simplicity of the measurement principle as well as the compactness of the
      measurement setup, light refractive tomography offers higher measurement
      performance and fewer error sources than light diffraction tomography. In this
      contribution, a numerically simulated ultrasound pressure field is exploited to
      determine the experimental parameters and to analyze the error sources as well as
      their influences on final results. After that, several ultrasound transducers
      excited with 1 MHz signals are investigated. The light refractive tomography
      results show good agreement with hydrophone measurements. Finally, we reconstruct
      2000 transient states of the ultrasound pressure field within a volume of about
      38 cm(3) after sending the burst signal. Without applying any smoothing to the
      resulting images, the reconstructed pressure field varies continuously in both
      spatial and temporal dimensions.

PMID- 22622977
TI  - Broadband generation of ultrasonic guided waves using piezoceramics and sub-band
      decomposition.
AB  - Classically, damage detection or dispersion curve determination using
      piezoceramic-generated guided waves has been based on analysis of propagation
      properties of multiple narrowband excitation signals. However, dispersion and
      multimodal propagation impair the determination of propagation properties. More
      recently, it has been proposed to consider broadband excitations for both damage
      imaging and group velocity estimation. Among existing transducer technologies,
      although laser excitation is prone to practical limitations in terms of
      dimensions and generated amplitudes, it allows generation of noncontact, point
      like broadband displacement. Thus, broadband generation of guided waves using
      piezoceramics can be envisioned. However, direct impulse response measurements
      are limited by the generated amplitude, leading to low SNR measurements. For this
      purpose, chirp excitations have been proposed using variable-frequency bursts,
      leading to phase and amplitude variations with respect to the frequency, such
      that this approach is not suitable for precise estimation of time of flight (ToF)
      or modal amplitude. In this paper, a sub-band decomposition technique that allows
      high-SNR measurements of impulse response in a given frequency range is proposed.
      Broadband excitation is decomposed over a given number of frequency sub-bands,
      generated by a piezoceramic element and measurement is performed using a laser
      Doppler vibrometer (LDV) or a piezoceramic sensor. Application to experimental
      estimation of group velocity and damage detection in pitchcatch configuration is
      proposed. It is shown that the proposed method allows damage estimation without a
      priori knowledge of the damage size, whereas narrowband techniques can fail at
      specific wavelengths.

PMID- 22622978
TI  - Effect of roughness on imaging and sizing rough crack-like defects using
      ultrasonic arrays.
AB  - All naturally occurring crack-like defects in solid structures are rough to some
      degree. Based on simulated array data for incident and scattered longitudinal
      waves from various rough cracks and the total focusing method (TFM) imaging
      algorithm, the effect of roughness on defect imaging and characterization is
      examined. The array data are simulated by using a previously validated model
      based on the Kirchhoff approximation to predict the rough crack scattering
      matrix. The scattering matrix describes the scattered field for all possible
      incident and scattering directions. The performance of TFM imaging for detecting
      rough crack-like defects is investigated by considering the averaged scattering
      coefficient over specified angular coverage ranges and the maximum scattered
      amplitude in the final image. It is shown that roughness can be either beneficial
      or detrimental to the detectability of a crack-like defect, depending on the
      defect characteristics, such as length, roughness, correlation length,
      orientation angle, and array inspection configuration. It is also shown that
      roughness can cause underestimation of the crack length if using an image-based
      approach for sizing.

PMID- 22622979
TI  - Guided wave expansion in warped curvelet frames.
AB  - Lamb wave testing for structural health monitoring (SHM) often relies on analysis
      of wavefields recorded through scanning laser Doppler vibrometers (SLDVs) or
      ultrasonic scanners. Damage detection and characterization with these techniques
      requires isolation of defect-induced reflections in the wavefield from the
      injected wave packet and from scattering events associated with structural
      features such as boundaries, rivets, joints, etc. This is a challenging task when
      dealing with complex structures and multimodal, dispersive propagation regimes,
      whereby various wave contributions in both the time/space and the
      frequency/wavenumber domain overlap. A new mathematical tool named warped
      curvelet frames (WCFs) is proposed to effectively decompose the recorded
      wavefields. The presented technique results from the combination of two
      operators, i.e., the curvelet transform (CT) and the warped frequency transform
      (WFT). The CT provides an optimally sparse representation of nondispersive wave
      propagators. Combining the CT with the WFT allows for a flexible analysis of
      multimodal wave propagation in dispersive media. Exploiting the spatial and
      temporal localization of curvelets, as well as the spectro-temporal adaptation of
      the analysis frame to the characteristics of each propagating mode, provided by
      frequency warping, a convenient decomposition of guided waves is achieved and
      relevant contributions can be effectively isolated. The proposed approach is
      validated through dedicated simulations and further tested experimentally to
      demonstrate the effectiveness of the method in separating guided wave modes
      corresponding to acoustic events in close spatial proximity.

PMID- 22622980
TI  - Extracting the electromechanical coupling constant of piezoelectric thin film by
      the high-tone bulk acoustic resonator technique.
AB  - In this paper, a new approach is proposed to rapidly and accurately measure the
      electromechanical coupling constant K(t)(2) of thin film piezoelectric material,
      which is critically important for real-time quality control of the piezoelectric
      film growth in mass production. An ideal lossy bulk acoustic resonator (LBAR)
      model is introduced and the theory behind the method is presented. A high-tone
      bulk acoustic resonator (HBAR) was fabricated on a silicon wafer. The impedance
      response of the resonator was measured, from which the K(t)(2) of the
      piezoelectric material was extracted. To illustrate the potential of the proposed
      technique to extract material properties, two HBAR devices employing AlN as the
      piezoelectric material were fabricated using an RF sputter system with known good
      and bad deposition conditions; the extracted K(t)(2) values of the piezoelectric
      material are compared.

PMID- 22622981
TI  - Biological sensor based on a lateral electric field-excited resonator.
AB  - This paper describes a biological sensor based on a lateral electric field
      excited resonator using an X-cut lithium niobate plate. Its potential was shown
      through the example of biological interaction between bacterial cells and
      specific bacteriophages. The detection was based on the analysis of the measured
      real and imaginary parts of electrical impedance for a resonator loaded by the
      biological suspension under study. It has been shown that the sensor is sensitive
      to specific interactions between bacterial cells and specific bacteriophages in a
      pure state as well as in the presence of extraneous microflora. The degree of
      electrical impedance variation resulting from the biological interaction depends
      on the numbers of phage particles and bacteria cells. The sensor may be used not
      only for the qualitative analysis of bacteria but also for their quantitative
      detection.

PMID- 22622982
TI  - Quantitative assessment on the orientation and distribution of carbon fibers in a
      conductive polymer composite using high-frequency ultrasound.
AB  - Conductive polymer composites, typically fabricated from a mix of conductive
      fillers and a polymer substrate, are commonly applied as bipolar plates in a fuel
      cell stack. Electrical conductivity is a crucial property that greatly depends on
      the distribution and orientation of the fillers. In this study, a 50-MHz
      ultrasound imaging system and analysis techniques capable of nondestructively
      assessing the properties of carbon fibers (CFs) in conductive polymer composites
      were developed. Composite materials containing a mix of polycarbonate substrates
      and 0 to 0.3 wt% of CFs were prepared using an injection molding technique.
      Ultrasonic A-line signals and C-scan images were acquired from each composite
      sample in regions at a depth of 0.15 mm beneath the sample surface (region A) and
      those at a depth of 0.3 mm (region B). The integrated backscatter (IB) and the
      Nakagami statistical parameter were calculated to quantitatively assess the
      samples. The area ratio, defined as the percentage of areas composed of CF images
      normalized by that of the whole C-scan image, was applied to further quantify the
      orientation of CFs perpendicular to the sample surface. Corresponding to the
      increase in CF concentrations from 0.1 to 0.3 wt%, the average IB and Nakagami
      parameter (m) of the composite samples increased from -78.10 +/- 2.20 (mean +/-
      standard deviation) to -72.66 +/- 1.40 dB and from 0.024 +/- 0.012 to 0.048 +/-
      0.011, respectively. The corresponding area ratios were respectively estimated to
      be 0.78 +/- 0.35%, 2.33 +/- 0.66%, and 2.20 +/- 0.60% in region A of the samples;
      those of CFs with a perpendicular orientation were 0.04 +/- 0.03%, 0.08 +/-
      0.02%, and 0.12 +/- 0.05%. The area ratios in region B of the samples were
      calculated to be 1.19 +/- 0.54%, 2.81 +/- 0.42%, and 2.64 +/- 0.76%, and those of
      CFs with a perpendicular orientation were 0.07 +/- 0.04%, 0.12 +/- 0.04%, and
      0.14 +/- 0.03%. According to the results of the orientations and ultrasonic
      images, CFs tended to distribute more uniformly in the deeper regions of the
      samples. This study validates that the distribution and orientation of CFs in
      conductive polymer composites could be sensitively and quantitatively assessed by
      high-frequency ultrasound in conjunction with current analysis methods.

PMID- 22622983
TI  - A U-shaped linear ultrasonic motor using longitudinal vibration transducers with
      double feet.
AB  - A U-shaped linear ultrasonic motor using longitudinal vibration transducers with
      double feet was proposed in this paper. The proposed motor contains a horizontal
      transducer and two vertical transducers. The horizontal transducer includes two
      exponential shape horns located at the leading ends, and each vertical transducer
      contains one exponential shape horn. The horns of the horizontal transducer and
      the vertical transducer intersect at the tip ends where the driving feet are
      located. Longitudinal vibrations are superimposed in the motor and generate
      elliptical motions at the driving feet. The two vibration modes of the motor are
      discussed, and the motion trajectories of driving feet are deduced. By adjusting
      the structural parameters, the resonance frequencies of two vibration modes were
      degenerated. A prototype motor was fabricated and measured. Typical output of the
      prototype is no-load speed of 854 mm/s and maximum thrust force of 40 N at a
      voltage of 200 V(rms).

PMID- 22622984
TI  - Theoretical modeling and equivalent electric circuit of a bimorph piezoelectric
      micromachined ultrasonic transducer.
AB  - An electric circuit model for a circular bimorph piezoelectric micromachined
      ultrasonic transducer (PMUT) was developed for the first time. The model was made
      up of an electric mesh, which was coupled to a mechanical mesh via a transformer
      element. The bimorph PMUT consisted of two piezoelectric layers of the same
      material, having equal thicknesses, and sandwiched between three thin electrodes.
      The piezoelectric layers, having the same poling axis, were biased with electric
      potentials of the same magnitude but opposite polarity. The strain mismatches
      between the two layers created by the converse piezoelectric effect caused the
      membrane to vibrate and, hence, transmit a pressure wave. Upon receiving the echo
      of the acoustic wave, the membrane deformation led to the generation of electric
      charges as a result of the direct piezoelectric phenomenon. The membrane angular
      velocity and electric current were related to the applied electric field, the
      impinging acoustic pressure, and the moment at the edge of the membrane using two
      canonical equations. The transduction coefficients from the electrical to the
      mechanical domain and vice-versa were shown to be bilateral and the system was
      shown to be reversible. The circuit parameters of the derived model were
      extracted, including the transformer ratio, the clamped electric impedance, the
      spring-softening impedance, and the open-circuit mechanical impedance. The
      theoretical model was fully examined by generating the electrical input impedance
      and average plate displacement curves versus frequency under both air and water
      loading conditions. A PMUT composed of piezoelectric material with a lossy
      dielectric was also investigated and the maximum possible electroacoustical
      conversion efficiency was calculated.

PMID- 22622985
TI  - Investigations on AlN/sapphire piezoelectric bilayer structure for high
      temperature SAW applications.
AB  - This paper explores the possibility of using AlN/sapphire piezoelectric bilayer
      structures for high-temperature SAW applications. To determine the temperature
      stability of AlN, homemade AlN/sapphire samples are annealed in air atmosphere
      for 2 to 20 h at temperatures from 700 to 1000 degrees C. Ex situ X-ray
      diffraction measurements reveal that the microstructure of the thin film is not
      affected by temperatures below 1000 degrees C. Ellipsometry and secondary ion
      mass spectroscopy investigations attest that AlN/sapphire is reliable up to 700
      degrees C. Beyond this temperature, both methods indicate ongoing surface
      oxidation of AlN. Additionally, Pt/Ta and Al interdigital transducers are
      patterned on the surface of the AlN film. The resulting SAW devices are
      characterized up to 500 degrees C and 300 degrees C, respectively, showing
      reliable frequency response and a large, quasi-constant temperature sensitivity,
      with a first-order temperature coefficient of frequency around -75 ppm/ degrees
      C. Between room temperature and 300 degrees C, both electromechanical coupling
      coefficient K(2) and propagation losses increase, so the evolution of delay
      lines' insertion losses with temperature strongly depends on the length of the
      propagation path.

PMID- 22622986
TI  - Thickness-shear vibration of an AT-cut quartz resonator with a hyperbolic
      contour.
AB  - A theoretical analysis is performed on thicknessshear vibrations of a contoured
      AT-cut quartz resonator with a hyperbolic thickness variation using the Legendre
      equation and hypergeometric function. Based on the solution, resonant frequencies
      and modes are calculated. Strong energy trapping of the modes is observed. The
      effects of the parameters of the hyperbolic contour on resonant frequencies and
      modes are examined. A comparison with the conventional contoured resonator in the
      literature with a quadratic thickness variation is made. The behaviors of the two
      types of resonators are qualitatively similar, with small but significant
      quantitative differences.

PMID- 22622987
TI  - Crystalline quality of the trigonal piezoelectric materials and effects of the
      extended defects.
AB  - Many frequently used or promising piezoelectric materials belong to crystal
      classes 32 or 3m. Among them are alpha quartz and its crystallographic analogs
      (AlPO(4), GaPO(4), alpha-GeO(2), etc.), the numerous materials of the langasite
      (La-(3)Ga(5)SiO,sub>14) family and also lithium tantalate (LiTaO,sub>3) and
      lithium niobate (LiNbO 3). In this paper we study the present state of the art
      for these materials, indicate their principal point and extended defects, and
      present methods to reduce the dislocation density. Large concentrations of
      intrinsic point defects often exist in crystal grown at very high temperatures.
      The point defects (intrinsic or related to impurities) modify the constants and
      can increase the acoustic losses. This is the case for the alkali ions and the OH
      that induce severe losses in different temperature intervals. The extended
      defects also affect the performances of the piezoelectric devices. Some, such as
      twins, ferroelectric domains, or large solid or liquid inclusions, have very
      detrimental effects. Dislocations, growth bands, and planar defects are more
      difficult to avoid and affect the devices in a more subtle manner. In quartz and
      its analogs, dislocations seem to increase the nonlinear elastic effects and have
      a collective effect on the vibration modes, particularly in energy trapping
      resonators. Growth bands and stacking faults also produce similar effects.

PMID- 22622988
TI  - Numerical modeling of piezoelectric transducers using physical parameters.
AB  - Design of ultrasonic equipment is frequently facilitated with numerical models.
      These numerical models, however, need a calibration step, because usually not all
      characteristics of the materials used are known. Characterization of material
      properties combined with numerical simulations and experimental data can be used
      to acquire valid estimates of the material parameters. In our design application,
      a finite element (FE) model of an ultrasonic particle separator, driven by an
      ultrasonic transducer in thickness mode, is required. A limited set of material
      parameters for the piezoelectric transducer were obtained from the manufacturer,
      thus preserving prior physical knowledge to a large extent. The remaining unknown
      parameters were estimated from impedance analysis with a simple experimental
      setup combined with a numerical optimization routine using 2-D and 3-D FE models.
      Thus, a full set of physically interpretable material parameters was obtained for
      our specific purpose. The approach provides adequate accuracy of the estimates of
      the material parameters, near 1%. These parameter estimates will subsequently be
      applied in future design simulations, without the need to go through an entire
      series of characterization experiments. Finally, a sensitivity study showed that
      small variations of 1% in the main parameters caused changes near 1% in the
      eigenfrequency, but changes up to 7% in the admittance peak, thus influencing the
      efficiency of the system. Temperature will already cause these small variations
      in response; thus, a frequency control unit is required when actually
      manufacturing an efficient ultrasonic separation system.

PMID- 22622989
TI  - Design and performance testing of an ultrasonic linear motor with dual
      piezoelectric actuators.
AB  - In this work, design and performance testing of an ultrasonic linear motor with
      dual piezoelectric actuator patches are studied. The motor system consists of a
      linear stator, a pre-load weight, and two piezoelectric actuator patches. The
      piezoelectric actuators are bonded with the linear elastic stator at specific
      locations. The stator generates propagating waves when the piezoelectric
      actuators are subjected to harmonic excitations. Vibration characteristics of the
      linear stator are analyzed and compared with finite element and experimental
      results. The analytical, finite element, and experimental results show agreement.
      In the experiments, performance of the ultrasonic linear motor is tested.
      Relationships between velocity and pre-load weight, velocity and applied voltage,
      driving force and applied voltage, and velocity and driving force are reported.
      The design of the dual piezoelectric actuators yields a simpler structure with a
      smaller number of actuators and lower stator stiffness compared with a
      conventional design of an ultrasonic linear motor with fully laminated
      piezoelectric actuators.

PMID- 22622990
TI  - Electrode-shaping for the excitation and detection of permitted arbitrary modes
      in arbitrary geometries in piezoelectric resonators.
AB  - This paper reports theoretical analysis and experimental results on a numerical
      electrode shaping design technique that permits the excitation of arbitrary modes
      in arbitrary geometries for piezoelectric resonators, for those modes permitted
      to exist by the nonzero piezoelectric coefficients and electrode configuration.
      The technique directly determines optimal electrode shapes by assessing the local
      suitability of excitation and detection electrode placement on two-port
      resonators without the need for iterative numerical techniques. The technique is
      demonstrated in 61 different electrode designs in lead zirconate titanate (PZT)
      thin film on silicon RF micro electro-mechanical system (MEMS) plate, beam, ring,
      and disc resonators for out-of-plane flexural and various contour modes up to 200
      MHz. The average squared effective electromechanical coupling factor for the
      designs was 0.54%, approximately equivalent to the theoretical maximum value of
      0.53% for a fully electroded length-extensional mode beam resonator comprised of
      the same composite. The average improvement in S(21) for the electrode-shaped
      designs was 14.6 dB with a maximum improvement of 44.3 dB. Through this
      piezoelectric electrodeshaping technique, 95% of the designs showed a reduction
      in insertion loss.

PMID- 22622991
TI  - Orthogonal quadratic chirp signals for simultaneous multi-zone focusing in
      medical ultrasound imaging.
AB  - In medical ultrasound imaging, multi-zone focusing on transmission is used to
      enhance the lateral resolution at the expense of frame rate. As an alternative,
      this paper proposes a simultaneous multi-zone focusing method using orthogonal
      quadratic chirp signals to improve lateral resolution without sacrificing frame
      rate. In the proposed method, two weighted quadratic chirp signals with different
      spectra are simultaneously transmitted with different transmit time delays for
      multi-zone focusing. Because the two weighted quadratic chirps can be designed to
      have a desired level of cross-correlation after compression, the degradation of
      axial resolution resulting from the division of a spectrum is minimized. Through
      simulation, the performances of the proposed method were evaluated and compared
      with those of two-cycle pulsed excitation as a gold standard and two sub-band
      weighted linear chirps. In the simulation, the proposed method improved -6-dB and
      -20-dB lateral beam widths by factors of 1.67 and 1.84, respectively, compared
      with the pulsed excitation. The degradation of axial resolution in the proposed
      method was maximally 43% less than that in the linear chirp case. The results
      demonstrate that the proposed method is useful in the improvement of overall
      ultrasound image quality because the axial resolution of conventional ultrasound
      images is generally a few times higher than the lateral resolution.

PMID- 22622992
TI  - Current practice in transvenous lead extraction: a European Heart Rhythm
      Association EP Network Survey.
AB  - AIM: Current practice with regard to transvenous lead extraction among European
      implanting centres was analysed by this survey. METHODS AND RESULTS: Among all
      contacted centres, 164, from 30 countries, declared that they perform transvenous
      lead extraction and answered 58 questions with a compliance rate of 99.9%. Data
      from the survey show that there seems to be an overall increasing experience of
      managing various techniques of lead extraction and a widespread involvement of
      cardiac centres in this treatment. Results and complication rates seem comparable
      with those of main international registries. CONCLUSION: This survey gives an
      interesting snapshot of lead extraction in Europe today and gives some clues for
      future research and prospective European registries.

PMID- 22622993
TI  - TLR-mediated distinct IFN-gamma/IL-10 pattern induces protective immunity against
      murine visceral leishmaniasis.
AB  - Resistance to murine visceral leishmaniasis (VL) correlates with the development
      of an IFN-gamma predominant immune response. Beta1,4-galactose terminal glycans
      are potent inducers of IFN-gamma. Here, we demonstrate the efficacy of a 29 kDa
      beta1,4-galactose terminal glycoprotein (GP29) of Leishmania donovani (LD) in an
      in vitro macrophage model and an in vivo mouse model of VL. GP29 induced splenic
      macrophages to release NO and ROS in appreciable amounts that resulted in
      effective parasite clearance from macrophages. This was associated with the toll
      like receptor (TLR)-4 mediated IL-12 induction and inhibition of TLR2-mediated IL
      10 production. Two subcutaneous injections of GP29 at fortnightly intervals
      resulted in dominant IL-12-mediated IFN-gamma production and 100% animals were
      protected against a subsequent challenge with virulent LD parasites. Vaccinated
      mice showed a reversal of T-cell anergy, significantly elevated expression of
      iNOS and a type-1 IgG subclass response. Moreover, vaccinated mice downregulated
      arginase1 and IL-10 expression but did not alter IL-4 expression. The IFN
      gamma/IL-10 ratio regulated the intensity of the protective immune response.
      Experiments with IFN-gamma and IL-10 knockout mice reiterated the role IL-10 and
      IFN-gamma play in disease progression or resolution in the murine model of VL.

PMID- 22622994
TI  - Modeling the effects of low-LET cosmic rays on electronic components.
AB  - The effects of cosmic radiation in single cells, organic tissues and electronics
      are a major concern for space exploration and manned missions. Standard heavy
      ions radiation tests employ ion cocktails with energy of the order of 10 MeV per
      nucleon and with a linear energy transfer ranging from a few MeV cm(2) mg(-1) to
      hundreds of MeV cm(2) mg(-1). In space, cosmic rays show significant fluxes at
      energies up to the order of GeV per nucleon. The present work aims at
      investigating single event damage due to low-, high- and very-high-energy ions.
      The European Space Agency reference single event upset monitor data are used to
      support the discussion. Finally, the effect of ionization induced directly by
      primary particles and ionization induced by recoils produced in an electronic
      device is investigated for different types of devices.

PMID- 22622995
TI  - Micronuclei in lymphocytes from currently active uranium miners.
AB  - Micronuclei can be used as markers of past radiation exposure, but only few
      studies have dealt with uranium miners. In this paper, we report on micronuclei
      in lymphocytes from individuals currently working at Rozna, Czech Republic, the
      last functioning uranium mine in the European Union. A modified micronucleus
      centromere test was applied to assess the occurrence of micronuclei in stimulated
      lymphocytes, as well as their content in terms of whole chromosomes or fragments.
      Compared with unexposed individuals, the miners had higher frequencies of
      micronucleus-containing lymphocytes and higher percentages of micronuclei without
      centromeres, and the differences were significant for both parameters (0.74 +/-
      0.60 vs. 0.50 +/- 0.42, p = 0.017 and 49 +/- 44 vs. 12 +/- 21, p = 0.0002; means
      +/- standard deviations). There were also significant correlations between one or
      other of these parameters on the one hand and various dose values on the other,
      in particular with a 'retrievable' dose, that is, a dose whose effect should
      still be recognisable in lymphocytes assuming a half-life of 3 years. The
      'retrievable' dose at which a doubling of the micronucleus frequency was observed
      was around 35 mSv, corresponding to a total dose of 90 mSv received while working
      in the mines. Altogether, our data show that the micronucleus-centromere test is
      a valuable tool for the assessment of past radiation exposure in uranium miners.
      The scatter in the data is of course far too great to allow individual dosimetry,
      but for groups of a few dozen exposed individuals, the method can be used to
      monitor doses clearly below 100 mSv.

PMID- 22622997
TI  - The corticotropin releasing factor system in the kidney: perspectives for novel
      therapeutic intervention in nephrology.
AB  - The adaptation to endogenous and exogenous stress stimuli is crucial for survival
      but also for the onset of various diseases in humans. Corticotropin releasing
      factor (CRF) system is the major regulator of stress response and homeostasis.
      The members of this family of peptides extend their actions also outside CNS to
      the periphery where they may affect various body systems independently, acting
      via vagal and/or autocrine/paracrine pathways. In search for peripheral targets,
      kidney has rarely been studied separately, regarding expression and action of CRF
      and CRF-related peptides. We reviewed the existing literature concerning
      expression and action of the CRF system in normal and pathological renal tissue
      and explored possible clinical implications in nephrology. CRF system components
      are expressed in the kidney of experimental animals and in humans. The intrarenal
      distribution is reported to be equally extensive, suggesting a physiological or
      pathophysiological role in renal function and in the occurrence of renal disease.
      Urocortins have given multiple interesting observations in experimental models of
      renal disease and clinical studies, showing robust effects in renal regulation
      mechanisms. We summarize the relevant data and put them in context, proposing
      applications with clinical significance in the field of hypertension, diabetic
      nephropathy, chronic kidney disease, cardiorenal syndrome, and peritoneal
      dialysis.

PMID- 22622996
TI  - Lung cancer mortality in the European uranium miners cohorts analyzed with a
      biologically based model taking into account radon measurement error.
AB  - The biologically based two-stage clonal expansion (TSCE) model is used to analyze
      lung cancer mortality of European miners from the Czech Republic, France, and
      Germany. All three cohorts indicate a highly significant action of exposure to
      radon and its progeny on promotion. The action on initiation is not significant
      in the French cohort. An action on transformation was tested but not found
      significant. In a pooled analysis, the results based on the French and German
      datasets do not differ significantly in any of the used parameters. For the Czech
      dataset, only lag time and two parameters that determine the clonal expansion
      without exposure and with low exposure rates (promotion) are consistent with the
      other studies. For low exposure rates, the resulting relative risks are quite
      similar. Exposure estimates for each calendar year are used. A model for random
      errors in each of these yearly exposures is presented. Depending on the used
      technique of exposure estimate, Berkson and classical errors are used. The
      consequences for the model parameters are calculated and found to be mostly of
      minor importance, except that the large difference in the exposure-induced
      initiation between the studies is decreased substantially.

PMID- 22622998
TI  - Rodlet cells development in the intestine of sea bass (Dicentrarchus labrax).
AB  - The enigmatic rodlet cells (RCs) are characterized by conspicuous inclusions
      named "rodlets". They were discovered over 100 years ago and were considered as
      parasites but shortly afterward interpreted as endogenous cells. The RCs have
      been described in different tissues of marine and freshwater teleosts, but their
      origin and function remain unknown. This work was designed to an ultrastructural
      study on RCs development and distribution in intestinal epithelium of
      Dicentrarchus labrax. Three different stages of RCs development from early
      precursor cells to mature phase were observed, as well as a migration and finally
      an extrusion of their contents. In this study, the immature cells were found near
      the basal epithelium membrane. They were mainly identified by a rough endoplasmic
      reticulum with dilated cisternae, by developing rodlets and a thin fibrillar
      coat. The maturing RCs, localized in the middle zone of the epithelium, appeared
      to be undergoing a reorganization of the cell organelles. The mature RCs, placed
      near the free surface, showed a thick subplasmalemmar fibrillar coat. Most of the
      organelles were aggregated at the cell apex with a basally located nucleus. A
      cellular polarity was more evident. One of the most conspicuous features was the
      occurrence of mature rodlets club-sac in shape orientated toward the cell apex.
      Adhesive junctions between surface epithelial cells and RCs, while discharging
      their contents, were seen. We have connected morphological figures and
      distribution to different stages of development in RCs, supporting the hypothesis
      of their secretory function.

PMID- 22622999
TI  - Five-year outcomes of CypherTM coronary stent: report from J-PMS Study.
AB  - The long-term outcome and compliance of dual-antiplatelet therapy after
      implantation of drug-eluting stent in the "real world" setting in Japan has not
      been well investigated. The purpose of this study was to provide information on
      the introduction and outcomes including status and compliance of dual
      antiplatelet therapy of sirolimus-eluting stent (SES). Five-year follow-up was
      achieved in 1937 of 2050 patients (94.5%). Off-label use was 87.3% in this study.
      The incidence of MACE was 23.2%, including death (13.4%), MI (3.4%), and target
      lesion revascularization (TLR, 9.6%). Multivariate analysis for TLR predicted
      dialysis [hazard ratio (HR) 3.5, 95% confidence interval (CI) 2.13-5.93], lesion
      length >30 mm (HR 1.89, 95% CI 1.24-2.84), vessel diameter <2.5 mm (HR 1.55, 95%
      CI 1.10-2.18), ostial lesion (HR 1.59, 95% CI 1.10-2.31), and previous PCI (HR
      1.42, 95% CI 1.00-2.00). There were 25 events of definite/probable thrombosis.
      Very late thrombosis was identified in 17 cases, and the slope of the linear
      portion of the cumulative incidence curve of stent thrombosis was 0.28% per year.
      Seven of the 17 events (41.2%) occurred under dual anti-platelet therapy. Five
      year outcomes after SES implantation in the "real world" in Japanese showed that
      dialysis, previous PCI, small vessel <2.5 mm, long lesion >30 mm, and ostial
      lesions were the predictors of TLR at 5-years. Stent thrombosis rate was lower
      than previous reports.

PMID- 22623000
TI  - The impact of preprocedural hemoglobin A1c on the efficacy of sirolimus-eluting
      and paclitaxel-eluting stents.
AB  - Several reports have shown contrary results regarding the efficacy of sirolimus
      eluting stents (SES) and paclitaxel-eluting stents (PES) in diabetic patients.
      The association between hemoglobin A1c (A1c) before coronary intervention and the
      midterm clinical outcomes of patients treated with these stents is unclear. The
      enrolled population was 415 patients with diabetes or impaired glucose tolerance
      (IGT) who underwent follow-up angiography after being implanted with a SES (n =
      282) or PES (n = 133). The enrolled population was classified into the optimal
      glycemic control group (n = 213) and suboptimal glycemic control group (n = 202),
      and the predictors of restenosis were examined in each group. In the optimal
      glycemic control group, the use of PES was an independent predictor of restenosis
      [odds ratio (OR) 9.98, 95% confidence interval (CI) 3.08-38.9, p < 0.0001]; on
      the other hand, the use of SES was a positive independent predictor of restenosis
      prevention (OR 0.10, 95% CI 0.03-0.32, p < 0.0001). In the suboptimal glycemic
      control group, neither stent was predictive of restenosis. In a subanalysis,
      preprocedural A1c (>=7.0%) was found to be an independent predictor of restenosis
      in the SES group (OR 3.61, 95% CI 1.14-12.8, p = 0.03), but not the PES group.
      Postprocedural A1c (>=7.0%) was not an independent predictor of restenosis in
      either stent group. This study showed that the superiority of SES compared to PES
      was attenuated in the suboptimal glycemic control group. Preprocedural A1c
      (>=7.0%) was found to be an independent predictor of restenosis in the SES group,
      but not in the PES group.

PMID- 22623001
TI  - Comparison of 3-year clinical outcomes after transradial versus transfemoral
      percutaneous coronary intervention.
AB  - Transradial approach is an established procedure in percutaneous coronary
      intervention (PCI). However, long term clinical outcomes of transradial PCI
      compared to transfemoral PCI have not been fully elucidated. Among 13087 patients
      undergoing first PCI in the CREDO-Kyoto registry Cohort-2 from January 2005 to
      December 2007, we identified 2736 patients with transradial approach and 4092
      patients with transfemoral approach, excluding patients with acute myocardial
      infarction, patients on dialysis and patients treated with transbrachial
      approach. Using propensity score methodology, 2701 patients with transfemoral
      approach were randomly matched to 2701 patients with transradial approach based
      on clinical, angiographic, and procedural characteristics. The rates for
      procedural success of PCI were high in both transradial and transfemoral PCI (99
      vs. 98%, P = 0.57). At 30 days, there was no significant difference in the
      incidence of all-cause death between the 2 groups (radial group 0.2% vs. femoral
      group 0.2%, P = 0.73). Incidence of bleeding event tended to be lower in the
      radial group than in the femoral group (1.0 vs. 1.6%, P = 0.09), and incidence of
      puncture site bleeding was significantly lower in the radial group than in the
      femoral group (0.2 vs. 0.6%, P = 0.005). Through 3-year follow up, cumulative
      incidence of all-cause death was not significantly different between the 2 groups
      (5.6 vs. 6.7%, hazard ratio 0.90 (95% confidence interval 0.71-1.13), P = 0.35].
      In conclusion, transradial PCI reduced 30-day puncture site bleeding event
      compared to transfemoral PCI, with similar PCI success rates. In contrast, 3-year
      mortality rate was comparable between transradial and transfemoral PCI.

PMID- 22623002
TI  - A case achieved successful revascularization to severe ischemic coronary artery
      disease after endovascular recanalization with infrarenal aortic occlusion.
AB  - An 80-year-old woman was admitted to our emergency department with ongoing
      dyspnea for 2 weeks. The patient was immediately intubated endotracheally because
      of the hypoxia with flush pulmonary edema. Electrocardiogram showed ST depression
      and echocardiogram showed hypokinesis of anterior left ventricular wall with poor
      systolic function. Also her cardiac enzymes were elevated, emergency coronary
      angiogram was performed from radial artery because both femoral arteries were not
      fully palpable. Coronary angiogram showed three vessels disease including chronic
      total occlusion of right coronary artery and left main bifurcation lesion. Also
      blood flow of left anterior descending coronary artery was delayed. Acute
      coronary syndrome was the cause of acute heart failure and revascularization was
      needed but aortography revealed total occlusion of infrarenal aorta. Patient was
      relatively hemodynamically stable; we planned treating total occlusion of
      infrarenal aorta with endovascular therapy to maintain a rout for cardiopulmonary
      support system. With bi-directional approach from both femoral artery and left
      brachial artery, occlusion site with heavy calcification was finally passed
      through by guide wire from retrograde approach. After pull-through technique,
      self-expanding nitinol stent was implanted after pre dilation with small balloon.
      Considering her EURO score, supposed perioperative mortality was high,
      percutaneous coronary intervention was performed. A 7 fr sheath was inserted from
      right femoral artery and intra-aortic balloon pump was inserted from left femoral
      artery. Sirolimus-eluting stent was implanted to left circumflex artery and also
      from ostium of left main to mid left anterior descending coronary artery after
      using an atherectomy device. After successful revascularization, patient became
      hemodynamically stable and weaning off the respirator was successful. Reporting
      case achieved successful revascularization to severe coronary artery disease
      after endovascular recanalization with infrarenal aortic occlusion.

PMID- 22623003
TI  - Coronary artery stenting in a patient with factor XI deficiency.
AB  - Factor XI deficiency is a rare inherited coagulopathy first described in
      Ashkenazi Jews. In Japanese populations, factor XI deficiency is thought to be
      very rare. This disorder causes unique problems during percutaneous coronary
      intervention (PCI). During PCI, prevention of thrombosis is important and heparin
      is usually used for anticoagulation. However, care must also be taken to avoid
      serious complications of bleeding. These two situations are contradictory and
      anticoagulation with heparin might increase severe bleeding in patients with
      factor XI deficiency. An 84-year-old Japanese woman was admitted to our hospital
      for the treatment of worsening effort angina pectoris. A coronary angiography
      revealed severe stenotic lesions at the left main trunk (LMT) and the right
      coronary artery (RCA). While performing PCI of the LMT, 8,000 U of heparin were
      used and the patient underwent successful drug-eluting stent implantation. At
      this point, the patient's activated coagulation time was over 1,500 s and there
      was a marked decrease of factor XI activity (<3%: normal range 75-145%). After
      the diagnosis of factor XI deficiency, PCI for the RCA was scheduled without
      anticoagulation and fresh frozen plasma instead of dual antiplatelet therapy by
      aspirin and clopidogrel. Two drug-eluting stents were deployed and dilation using
      the kissing balloon technique was performed. The procedure was uneventful without
      stent thrombosis or distal embolization or bleeding. Because the literature on
      stenting for patients with factor XI deficiency is very limited, this case
      provides additional clinical information.

PMID- 22623004
TI  - Mother-and-child technique using 4-Fr inner catheter for stent delivery during
      provisional stenting.
AB  - Provisional stenting is the most common strategy in the treatment of bifurcated
      lesions. However, such a situation as the failure in additional stent deployment
      to the side branch through the stent strut is occasionally encountered. In this
      paper, we report on two cases, in which we managed to successfully cross an
      additional stent to the angulated side branch through the stent strut using the
      four-in-six system after failed attempts using conventional techniques. This
      system will allow us to perform provisional stenting more easily.

PMID- 22623005
TI  - Inferior acute myocardial infarction due to acute cardiac herniation after right
      pneumonectomy.
AB  - A 69-year-old man underwent right intrapericardial pneumonectomy for lung cancer.
      After 24 h, he went into shock with inferior acute myocardial infarction. We
      performed urgent coronary angiography, which revealed total occlusion of the mid
      right coronary artery. Intravascular ultrasound showed that the artery seemed to
      be compressed from the pericardial side. We implanted a coronary stent because
      the lesion was refractory to balloon dilatation. After the procedure, we
      performed computed tomography and cardiac herniation was diagnosed. Emergency
      thoracotomy was performed to return the herniated heart to its normal position.
      This patient was discharged 38 days after initial surgery.

PMID- 22623006
TI  - A rare complication with remarkable stent shortening and successful recovery from
      the trouble.
AB  - Deployed coronary stent distortion is a rare complication, but can potentially
      occur during coronary intervention. We herein report a rare complicated case with
      remarkable stent distortion of longitudinal stent shortening and successful
      recovery from a trouble using a Corsair microcatheter.

PMID- 22623007
TI  - Preventing a central nervous system catastrophe in a case of Takayasu's arteritis
      presenting with critical stenosis of all three arch vessels.
AB  - Multifocal and bilateral involvement of the arch vessels is a common presentation
      of Takayasu's arteritis. Endovascular stenting of multiple supra aortic lesions
      in Takayasu's arteritis has been described scarcely in literature. We describe
      the management of a case of Takayasu's arteritis who presented with recurrent
      vertebro-basilar symptoms and a single surviving arch vessel. Whether routine
      revascularization of all three vessels is superior to symptom driven
      revascularization of individual lesions remains uncertain. The abundant
      collateral blood flow; the problems with stenting during the acute phase of the
      disease; the risk of restenosis that is considerably higher than atherosclerotic
      lesions; and the chances of progression of the disease have to be taken into
      account during endovascular revascularization of multiple supra aortic arch
      vessels.

PMID- 22623008
TI  - Premenopausal woman with acute myocardial infarction caused by spontaneous
      coronary artery dissection and potential association with coronary vasospasm.
AB  - A 45-year-old premenopausal woman presented with acute myocardial infarction
      (MI). An intravascular ultrasound (IVUS) revealed that her distal right coronary
      artery was occluded by spontaneous coronary artery dissection (SCAD). She did not
      have any specific condition related to SCAD. At follow-up cardiac
      catheterization, an acetylcholine provocation test was applied to examine the
      etiology of SCAD, and definitive coronary vasospasm was induced with chest
      symptoms and significant electrocardiographic change. A Ca-channel blocker was
      administered and since then chest pain has subsequently so far been relieved. The
      current case suggests the significance of the IVUS in detecting etiology of MI in
      younger patients and the potential association between SCAD and coronary
      vasospasm.

PMID- 22623009
TI  - Multiple coronary to pulmonary artery fistulas: a case report and review of the
      literature.
AB  - Coronary to pulmonary artery fistulae (CAF) are rare cardiac anomalies. The
      majority arise from the right coronary artery, with fistulae originating from the
      left anterior descending artery or from multiple arteries being less common. CAF
      are frequently asymptomatic and found incidentally on routine cardiac imaging. We
      present the case of a 61-year-old woman with multiple CAF who presented with
      progressive shortness of breath and chest pain and was ultimately treated
      successfully with trans-catheter coiling with marked improvement in symptoms. We
      also review the currently available literature regarding advances in diagnosis
      and treatment of CAF.

PMID- 22623010
TI  - Successful outside-the-stent stenting for in-stent chronic total occlusion in the
      common iliac artery.
AB  - Several studies showed durable long-term clinical benefit of endovascular therapy
      with stenting in aorto-iliac occlusive disease. Although in-stent restenosis is
      easily treated in routine practice, we experienced an uncommon case of failed
      reconstitution of in-stent total occlusion at the common iliac artery (CIA). The
      case was treated with nitinol stent implantation outside of the in-stent
      occlusion site, and good vessel patency was observed at 14 months after the
      procedure. Nitinol stent implantation outside of an in-stent occlusion in the CIA
      is a novel reconstitution strategy when the guide wire cannot pass the occlusion
      site within a previously implanted stent.

PMID- 22623011
TI  - IVUS guidance in percutaneous closure of aortic paraprosthetic leak.
AB  - Severe aortic regurgitation due to paraprosthetic leak appears in 1-5% of
      patients with previous aortic valve replacement. Surgical management is the
      treatment of choice but has high morbidity and mortality and leak recurrence is
      not uncommon. Different approaches to percutaneous closure have been tried.
      Transesophageal echocardiography (TEE) is a key factor to measure and localize
      leakages. Performing TEE during the procedure implies general anesthesia and
      prolongs procedure and fluoroscopy times. We report the case of an aortic
      paraprosthetic leak percutaneous closure using intravascular ultrasound to guide
      the procedure.

PMID- 22623012
TI  - What is the best reference state for designing statistical atomic potentials in
      protein structure prediction?
AB  - Many statistical potentials were developed in last two decades for protein
      folding and protein structure recognition. The major difference of these
      potentials is on the selection of reference states to offset sampling bias.
      However, since these potentials used different databases and parameter cutoffs,
      it is difficult to judge what the best reference states are by examining the
      original programs. In this study, we aim to address this issue and evaluate the
      reference states by a unified database and programming environment. We
      constructed distance-specific atomic potentials using six widely-used reference
      states based on 1022 high-resolution protein structures, which are applied to
      rank modeling in six sets of structure decoys. The reference state on random-walk
      chain outperforms others in three decoy sets while those using ideal-gas, quasi
      chemical approximation and averaging sample stand out in one set separately.
      Nevertheless, the performance of the potentials relies on the origin of decoy
      generations and no reference state can clearly outperform others in all decoy
      sets. Further analysis reveals that the statistical potentials have a
      contradiction between the universality and pertinence, and optimal reference
      states should be extracted based on specific application environments and decoy
      spaces.

PMID- 22623014
TI  - Liquid crystalline nanostructures: organizing matrices for non-enzymatic nucleic
      acid polymerization.
AB  - When a mixture of amphiphilic compounds and solute molecules undergoes
      dehydration, a liquid crystalline multilamellar matrix is produced that organizes
      and concentrates solute molecules between lamellae. If the solutes are
      nucleotides, RNA-like molecules can be synthesized by a condensation reaction
      when the system is exposed to one or more cycles of dehydration at elevated
      temperatures, followed by rehydration. The chemical potential driving the
      reaction is supplied by the anhydrous conditions in which water becomes a leaving
      group, with heat providing activation energy. Liquid crystalline matrices
      composed of amphiphilic compounds could have promoted polymerization reactions in
      prebiotic conditions, giving rise to the molecular complexity required for the
      origin of cellular life.

PMID- 22623013
TI  - Optimization strategies for evaluation of brain hemodynamic parameters with qBOLD
      technique.
AB  - Quantitative blood oxygenation level dependent technique provides an MRI-based
      method to measure tissue hemodynamic parameters such as oxygen extraction
      fraction and deoxyhemoglobin-containing (veins and prevenous part of capillaries)
      cerebral blood volume fraction. It is based on a theory of MR signal dephasing in
      the presence of blood vessel network and experimental method-gradient echo
      sampling of spin echo previously proposed and validated on phantoms and animals.
      In vivo human studies also demonstrated feasibility of this approach but also
      recognized that obtaining reliable results requires high signal-to-noise ratio in
      the data. In this paper, we analyze in detail the uncertainties of the
      quantitative blood oxygenation level dependent parameter estimates in the
      framework of the Bayesian probability theory, namely, we examine how the
      estimated parameters oxygen extraction fraction and deoxygenated cerebral blood
      volume fraction depend on their "true values," signal-to-noise ratio, and data
      sampling strategies. On the basis of this analysis, we develop strategies for
      optimization of the quantitative blood oxygenation level dependent technique for
      deoxygenated cerebral blood volume and oxygen extraction fraction evaluation. In
      particular, it is demonstrated that the use of gradient echo sampling of spin
      echo sequence allows substantial decrease of measurement errors as the data are
      acquired on both sides of spin echo. We test our theory on phantom mimicking the
      structure of blood vessel network. A 3D gradient echo sampling of spin echo pulse
      sequence is used for the acquisition of the MRI signal that was subsequently
      analyzed by Bayesian Application Software. The experimental results demonstrated
      a good agreement with theoretical predictions.

PMID- 22623015
TI  - A case of adult-onset Still's disease complicated by thrombotic thrombocytopenic
      purpura with retinal microangiopathy and rapidly fatal cerebral edema.
AB  - We present a patient who had adult-onset Still's disease (AOSD) complicated by
      thrombotic thrombocytopenic purpura (TTP) that resulted in retinal
      microangiopathy and rapidly fatal cerebral edema. The patient was a 37-year-old
      male who developed fever, eruption, arthritis and hepatic dysfunction, that,
      based on close examination, was diagnosed as AOSD. Despite treatment with
      corticosteroids, the patient developed acute visual field defect, neurological
      deterioration including convulsions and impaired consciousness, as well as acute
      renal failure that ultimately resulted in death. Pathological examination of
      autopsy specimens revealed multiple fibrin thrombi disseminated in small vessels
      of the brain and kidney, which was consistent with TTP, along with marked
      cerebral edema. Although TTP has rarely been reported in association with AOSD,
      awareness of the possible coexistence of these two diseases is important for
      diagnosis and treatment.

PMID- 22623016
TI  - Pharmacodynamic profile of tramadol in humans: influence of naltrexone
      pretreatment.
AB  - RATIONALE: Tramadol is a prescription analgesic that activates mu opioid and
      monoamine receptor systems. Tramadol is thought to have limited abuse potential
      compared to mu opioid agonists, but laboratory data indicate that it shares some
      of their pharmacodynamic effects. OBJECTIVES: This study evaluated the effect of
      mu opioid receptor blockade with naltrexone on the pharmacodynamic action of
      tramadol in humans. METHODS: This inpatient, double-blind, randomized, within
      subject study examined the effects of oral placebo, tramadol (87.5, 175, and 350
      mg), and hydromorphone (4 and 16 mg; positive control) after 1 h pretreatment
      with oral naltrexone (0 and 50 mg). Ten recreational opioid users completed the
      study. Pharmacodynamic effects were measured before and for 7 h after initial
      drug administration. RESULTS: Lower doses of tramadol and hydromorphone were
      generally placebo-like. Hydromorphone (16 mg) produced prototypic mu opioid
      agonist-like effects that were blocked by naltrexone. Tramadol (350 mg) produced
      miosis and increased ratings of "Good Effects" and "Liking" but also increased
      ratings of "Bad Effects." Naltrexone reversed tramadol-induced physiological
      effects and mydriasis emerged, but unlike results with hydromorphone, naltrexone
      only partially attenuated tramadol's positive subjective effects and actually
      enhanced several unpleasant subjective ratings. CONCLUSIONS: Naltrexone can be
      used to disentangle the mixed neuropharmacological actions of tramadol. High-dose
      tramadol produces a mixed profile of effects. These data suggest that both mu and
      non-mu opioid actions play a role in tramadol's subjective profile of action.

PMID- 22623018
TI  - Development of budesonide nanocluster dry powder aerosols: preformulation.
AB  - Wet milling was previously demonstrated as a simple process for producing
      agglomerates of budesonide nanoparticles (also known as NanoClusters) for use in
      dry powder aerosol formulation. The resulting budesonide NanoCluster powders
      exhibited a large emitted fraction and a high fine particle fraction (FPF) from a
      Monodose(r) dry powder inhaler. In this work, excipients were added premilling or
      postmilling and the performance of budesonide NanoCluster dry powders was
      investigated. Sodium chloride, Pluronic(r), or ethanol was added prior to milling
      due to their ability to modify surface tension or ionic strength and thereby
      affect the attrition/agglomeration process. Lactose or l-leucine was added after
      milling because these are known to modify powder flow and dispersion. The
      chemical stability of budesonide was maintained in all cases, but the physical
      aerosol properties changed substantially with the addition of excipients. In all
      cases, the addition of excipients led to an increase in the size of the
      budesonide NanoClusters and tended to reduce the emitted fraction and FPF.
      Titrating excipients may provide a means to discretely modify the aerosol
      properties of budesonide NanoClusters but did not match the performance of
      excipient-free NanoCluster powder.

PMID- 22623019
TI  - The value of juvenile animal studies "What have we learned from preclinical
      juvenile toxicity studies? II".
AB  - Recent changes in the regulations from the FDA and EMA have shifted the focus of
      juvenile toxicity studies more to the safe use of all pharmaceuticals and the
      absence of label or safety information for the pediatric population. Unlike other
      regulatory guidance, the need or design of these animal studies is not specified.
      Ideally these should be decided "case-by-case" based on the patient population,
      pharmacology, existing toxicological and clinical data, dosing regimen, and
      developing system impact. Following the publishing of a small intercompany survey
      (Bailey and Marien, 2009), a more extensive survey was commissioned by the
      ILSI/HESI DART Technical Committee to clarify what has been learned for the
      safety assessment for pediatrics. Contributions from 24 companies totaling 241
      studies (84% rat and 14% dog) were received. In 12 of 82 programs (15%) were the
      existing adult preclinical or clinical data considered a sufficient safety
      prediction for pediatric trials. Clinical/preclinical correlates were observed in
      17.2% (rat) and 42.9% (dog) of the studies and a lack of predictability from the
      pharmacology or the adult toxicity data was seen in 25% of rat and 14.3% of dog
      studies. Many of the studies were large, lengthy, complex, included parameters
      that mirrored the adult studies and yielded no new or useful information. We
      should avoid conducting complex or inappropriate studies and Contract Research
      Organisations and regulatory agencies have a role in encouraging more targeted
      designs. Only with appropriate designs can we adequately identify safety or
      pharmacokinetic issues, suggest clinical endpoints, and contribute to the product
      label.

PMID- 22623017
TI  - Serotonin transporter-linked polymorphic region (5-HTTLPR) genotype is associated
      with cortisol responsivity to naloxone challenge.
AB  - RATIONALE: The serotonergic and opioidergic neurotransmitter systems are critical
      regulators of the hypothalamic-pituitary-adrenal (HPA) axis through their
      respective excitatory and inhibitory inputs. Serotonin transporter (5-HTT)
      genotype has been studied as a marker of HPA axis dysregulation and for
      predicting risk of psychopathology, with mixed findings. OBJECTIVES: We
      stimulated the HPA axis with naloxone, an opioid receptor antagonist, to examine
      cortisol reactivity based on 5-HTT-linked polymorphic region (5-HTTLPR)
      genotypes. METHODS: Healthy community volunteers (N = 78) received intravenous
      (IV) placebo followed by sequential doses of IV naloxone (50, 100, 200, and 400
      MUg/kg) every 30 min. Plasma cortisol was measured every 15 min. Participants
      were genotyped for the long (L) and short (S) alleles of the 5-HTT gene and for
      rs25531 (A/G) in the 5-HTTLPR repetitive element and compared by the 5
      HTTLPR/rs25531 genotype (triallele) and by the 5-HTTLPR genotype (biallele)
      classification. RESULTS: In triallele analyses, individuals with one or more L(A)
      alleles showed higher cortisol response to naloxone compared with individuals
      with no L(A) alleles. In biallele analyses, less robust effects were found,
      although individuals with two L alleles showed a higher cortisol response
      compared with other genotypes. CONCLUSIONS: Naloxone blockade leads to a greater
      activation of the HPA axis among individuals with the L(A) allele. Including
      rs25531 in the analysis with the 5-HTTLPR genotype appears more sensitive in
      detecting genetic differences in naloxone-induced cortisol than when using only
      the 5-HTTLPR genotype. Future research should investigate the interactive effects
      between the serotonergic and opioidergic systems on HPA axis dysregulation and
      psychopathophysiology.

PMID- 22623020
TI  - Value of juvenile animal studies.
AB  - The Developmental and Reproductive Toxicology Technical Committee of the ILSI
      Health and Environmental Sciences Institute has undertaken a project to address
      the impact of juvenile animal studies on pediatric drug development. A workshop,
      sponsored and organized by the Health and Environmental Sciences Institute
      Developmental and Reproductive Toxicity Technical Committee, was held on May 5-6,
      2010, in Washington, DC, to discuss the outcome of a global survey and the value
      of juvenile animal studies in the development of drugs intended for use in
      pediatric patients. During this workshop, summary data from the 2009-2010 survey
      were presented, and breakout sessions were used to discuss specific case studies
      to try to assess the impact of juvenile animal studies performed to support
      specific pediatric drug development. The objectives of the Workshop on The Value
      of Juvenile Animal Studies were to (1) provide a forum for scientists
      representing industry, academia, and regulatory agencies to discuss the impact of
      juvenile animal studies on pediatric drug development, (2) evaluate summary data
      from the survey to understand how the juvenile study data are being used and
      their impact in labeling and risk assessment, (3) discuss selected case studies
      from the survey to highlight key findings, and (4) identify the areas of
      improvement for the designs of juvenile animal studies. The take home message
      that resonated from the workshop discussions was that well-designed juvenile
      animal studies have demonstrated value in support of certain pediatric drug
      development programs. However, it was also clear that a juvenile animal study is
      not always warranted.

PMID- 22623021
TI  - Insulin resistance in children with primary nephrotic syndrome and normal renal
      function.
AB  - BACKGROUND: Insulin resistance (IR) is an independent risk factor for
      atherosclerosis or cardiovascular events and renal function impairment. The aim
      of this study was to investigate IR in children with primary nephrotic syndrome
      (NS). METHODS: One-hundred and nineteen primary NS patients with normal renal
      function and 125 normal controls were studied. Fasting blood glucose, fasting
      serum insulin, and fasting serum C-peptide were measured. The Homa index of
      insulin resistance (HOMA-IR), Islet B cell function, and insulin sensitivity
      index were calculated. Correlations were assessed between HOMA-IR, fasting serum
      C-peptide, blood pressure, blood lipids, renal function, coagulation, clinical
      disease type, pathology and the early therapeutic effectiveness of high-dose
      glucocorticoids. RESULTS: There was no evidence of IR in the primary NS group.
      Although levels of fasting blood glucose, fasting serum insulin and fasting serum
      C-peptide were all within the normal ranges, fasting serum C-peptide was
      significantly higher compared to the controls. There was no disorder of
      carbohydrate metabolism in different hormone therapy efficacy and pathological
      diagnosis. Although IR was not detected, a significant increase in blood
      pressure, uric acid, blood lipids and coagulability was observed in the primary
      NS group. CONCLUSION: A correlation observed between HOMA-IR, age, blood
      pressure, serum creatinine (Cr) and triglyceride may suggest that insulin
      sensitivity will emerge as renal disease progresses. Fasting serum C-peptide
      levels were increased in the primary NS group, suggesting that fasting serum C
      peptide may be a protective factor.

PMID- 22623022
TI  - Effect of placebo on ambulatory blood pressure monitoring in children.
AB  - BACKGROUND: Ambulatory blood pressure monitoring (ABPM) has been proposed as a
      useful tool for more accurately diagnosing hypertension (HTN) and evaluating
      blood pressure (BP) response in pediatric anti-hypertensive trials. ABPM captures
      multiple BP measurements during routine daily activities and is thus an excellent
      method for identifying white-coat HTN. Additionally, ABPM measurements in adults
      do not demonstrate the placebo effect commonly seen with casual BP measurements,
      although this has yet to be evaluated in children. Therefore,, the aim of this
      study was to assess the effect of placebo on ABPM measurements in children.
      METHODS: A total of 141 children aged 5-16 years with elevated BP were randomized
      into a multi-center, single-blind, cross-over trial. Subjects received a placebo
      pill prior to wearing a 24-h ABPM device at one of two visits separated by 1-2
      weeks. Study procedures were otherwise identical at both visits. RESULTS: Mean
      systolic and diastolic BP for all measured time periods were similar between
      visits, as was the number of children diagnosed with HTN at each visit.
      CONCLUSION: Having confirmed HTN at baseline did not affect the impact of placebo
      on mean BP. If confirmed, this lack of placebo effect on ABPM measurements may
      allow for the design of direct comparison pediatric anti-hypertensive trials
      without a placebo arm.

PMID- 22623023
TI  - A single bout of exercise increases the expression of glucose but not fatty acid
      transporters in skeletal muscle of IL-6 KO mice.
AB  - IL-6 is a biologically active cytokine released during exercise by contracting
      skeletal muscles. It appears to be highly involved in the regulation of muscles
      energy substrate utilization. Whether an ablation of IL-6 (IL-6 KO) in mice
      subjected to a single bout of exercise affects lipid and/or glucose metabolism is
      currently unknown. In the present study we examined fatty acid (FAT/CD36, FABPpm,
      FATP-1, FATP-4) as well as glucose (GLUT-1, GLUT-4) transporters expression in IL
      6 KO mice. In addition, intramuscular glycogen and lipid content was also
      evaluated. The expression of all fatty acid transporters (FAT/CD36: +25 %; FATP
      1: +31 %; FABPpm: +12.7 %; FATP-4: +7.2 %) was increased in muscles from IL-6 KO
      mice compared to wild type (WT) mice. Accordingly intramuscular lipid content was
      also increased in these muscles (FFA: +38 %; DAG: +36 % and TAG: +160 %).
      Interestingly, IL-6 deficiency had only minor effect on glucose transporters
      expression (GLUT-1: -4 %, and GLUT-4: -5.1 %), with no apparent difference in
      muscular glycogen content. A single bout of exercise increased the glucose
      transporters (GLUT-1: +8 %; GLUT-4: +15 %) as well as FA transporters (FAT/CD36:
      +13 %; FABPpm: +4.5 %; FATP: +2.5 %, FATP-4: +10 %) expression but only in WT
      skeletal muscles. In muscles from IL-6 KO mice exercise induced changes only in
      glucose (GLUT-1: +20 %; GLUT-4: +35 %) but not in the content of FA transporters.
      Concomitantly, IL-6 KO mice displayed shorter time toward exhaustion with more
      pronounced reductions in intramuscular lipid and glycogen content. We may
      speculate, that IL-6 deficiency provokes more pronounced glucose utilization over
      lipid oxidation during a single bout of exhausting exercise.

PMID- 22623027
TI  - Univalent gallium and indium phosphane complexes: from pyramidal M(PPh3)3(+) to
      carbene-analogous bent M(PtBu3)2(+) (M=Ga, In) complexes.
AB  - In a new oxidative route, Ag(+)[Al(OR(F))(4)](-) (R(F)=C(CF(3))(3)) and metallic
      indium were sonicated in aromatic solvents, such as fluorobenzene (PhF), to give
      a precipitate of silver metal and highly soluble [In(PhF)(n)](+) salts (n=2, 3)
      with the weakly coordinating [Al(OR(F))(4)](-) anion in quantitative yield. The
      In(+) salt and the known analogous Ga(+)[Al(OR(F))(4)](-) were used to synthesize
      a series of homoleptic PR(3) phosphane complexes [M(PR(3))(n)](+), that is, the
      weakly PPh(3)-bridged [(Ph(3)P)(3)In-(PPh(3))-In(PPh(3))(3)](2+) that essentially
      contains two independent [In(PPh(3))(3)](+) cations or, with increasing bulk of
      the phosphane, the carbene-analogous [M(PtBu(3))(2)](+) (M=Ga, In) cations. The
      M(I)-P distances are 27 to 29 pm longer for indium, and thus considerably longer
      than the difference between their tabulated radii (18 pm). The structure,
      formation, and frontier orbitals of these complexes were investigated by
      calculations at the BP86/SV(P), B3LYP/def2-TZVPP, MP2/def2-TZVPP, and SCS
      MP2/def2-TZVPP levels.

PMID- 22623026
TI  - Experimental and computational analysis of cellular interactions with nylon-3
      bearing substrates.
AB  - The ability to design biomaterials that interact with biological environments in
      a predictable manner necessitates an improved understanding of how surface
      chemistry influences events such as protein adsorption and cell adhesion. In this
      work, we examined mechanisms governing the interactions between 3T3 fibroblasts
      and nylon-3 polymers, which have a protein-like polyamide backbone and are highly
      amenable to tuning of chemical and physical properties. Protein adsorption and
      cell adhesion to a library of nylon-3 polymers were characterized and analyzed by
      partial least squares regression. This analysis revealed that specific chemical
      features of the nylon-3 polymers correlated with the extent of protein
      adsorption, which, in turn, correlated with cell adhesion in a serum-containing
      environment. In contrast, in a serum-free environment, cell adhesion could be
      predicted solely from chemical properties. Enzymatic treatments of 3T3 cells
      before plating indicated that proteins bound to the cell surface mediated cell
      nylon-3 polymer interactions under serum-free conditions, with additional
      analysis suggesting that cell-associated fibronectin played a dominant role in
      adhesion in the absence of serum. The mechanistic insight gained from these
      studies can be used to inform the design of new polymer structures in addition to
      providing a basis for continued development of nylon-3 copolymers for tissue
      engineering applications.

PMID- 22623025
TI  - Molecular mechanisms underlying the fetal programming of adult disease.
AB  - Adverse events in utero can be critical in determining quality of life and
      overall health. It is estimated that up to 50 % of metabolic syndrome diseases
      can be linked to an adverse fetal environment. However, the mechanisms linking
      impaired fetal development to these adult diseases remain elusive. This review
      uncovers some of the molecular mechanisms underlying how normal physiology may be
      impaired in fetal and postnatal life due to maternal insults in pregnancy. By
      understanding the mechanisms, which include epigenetic, transcriptional,
      endoplasmic reticulum (ER) stress, and reactive oxygen species (ROS), we also
      highlight how intervention in fetal and neonatal life may be able to prevent
      these diseases long-term.

PMID- 22623028
TI  - The diagnostic accuracy of multidetector computed tomography with multiplanar
      reformatted imaging and virtual cystoscopy in the early detection and evaluation
      of bladder carcinoma: comparison with conventional cystoscopy.
AB  - PURPOSE: To evaluate the diagnostic accuracy of multidetector computed tomography
      (MDCT) with multiplanar reformatted imaging and virtual cystoscopy (VC) in early
      detection and evaluation of bladder masses with comparison with conventional
      cystoscopic findings. MATERIALS AND METHODS: This prospective study included 35
      patients with suspected bladder cancer were studied by computed tomographic
      cystography (CTC) and virtual cystography (VC) in both the supine and prone
      positions after distending the bladder with air. The patient population was
      divided into three groups based on lesion size at conventional cystoscopy (CC).
      Results of the CT study were compared with those of CC. MAIN OUTCOME MEASURES:
      Sensitivity, specificity, positive, and negative predictive value was used to
      study the association between VC and CC as regarding lesion detection. RESULTS:
      The size of the tumors varied from 2 mm to occupying more than three quarters of
      the bladder. Of the 71 lesions detected on CC, 47 lesions were positive in
      histopathology, 28 were <4 mm (19 were positive and 9 were negative for
      neoplasia), and four of these were missed on VC, with one of 3 mm missed on CC
      and correctly located by VC. Thus, all lesions of >4 mm were detected by VC and
      24 of 28 <4 mm. The locations of all were correctly described at VC when compared
      with CC. The overall sensitivity of VC vs. CC was 94.36%, specificity 71.42%, PPV
      was 97.1%, and NPV was 55.55%. CONCLUSION: Cystoscopy remains the standard of
      reference for the evaluation of the urinary bladder, but MDCT is indicated for
      examination of patients on whom CC is contraindicated, difficult to perform,
      unsatisfactory in interpretation, and as an adjuvant tool in the evaluation of
      areas difficult to assess with CC.

PMID- 22623029
TI  - Complications of Whipple surgery: imaging analysis.
AB  - BACKGROUND/AIMS: The purpose of this article is to describe and illustrate
      anatomic findings after the Whipple procedure, and the appearance of its
      complications, on imaging. CONCLUSION: Knowledge of the cross-sectional anatomy
      following the Whipple procedure, and clinical findings for associated
      complications, are essential to rapidly and accurately diagnose such
      complications on postoperative studies in order to optimize treatment.

PMID- 22623030
TI  - A novel whole tooth-in-jaw-bone culture of rat molars: morphological,
      immunohistochemical, and laser capture microdissection analysis.
AB  - In conventional whole-tooth culture systems, limitation exists regarding
      maintenance of the vitality of the dental pulp, because this tissue is encased in
      rigid dentin walls that hinder nutrition supply. We here report a whole tooth-in
      jaw-bone culture system of rat mandibular first molars, where transcardiac
      perfusion with culture medium was carried out before placement of the jaw bone
      into culture medium, aiming to facilitate longer time preservation of the dental
      pulp tissue. Following 7 days of culture, the pulp tissues were analyzed by
      histology and immunohistochemistry to ED2 (antiresident macrophage). ED2-positive
      macrophages were also analyzed for their Class II MHC, interleukin-6 (IL-6), and
      p53 mRNA expression levels by means of immune-laser capture microdissection
      (immune-LCM). Dentin sialophosphoprotein (DSPP) mRNA expression in odontobalstic
      layer was also examined by LCM. Teeth cultured following saline-perfusion and
      nonperfusion served as cultured controls. Normal teeth also served as noncultured
      controls. Histological examination demonstrated that the structure of the pulp
      tissue was well preserved in the medium-perfused explants in contrast to the
      cultured control groups. The Class II MHC, IL-6, and p53 mRNA expression levels
      of ED2-positive cells and DSPP expression levels of odontoblastic layer tissues
      in the pulp of medium-perfused explants were not significantly different from
      those in the noncultured normal teeth. In conclusion, the structural integrity
      and mRNA expression in the pulp were maintained at the in vivo level in the ex
      vivo whole tooth-in-jaw-bone culture system. The system may lay the foundation
      for studies aiming at defining further histological and molecular mechanism of
      the pulp.

PMID- 22623031
TI  - Synthesis, crystal structure of alpha-Keggin heteropolymolybdates with pyridine
      2,6-dicarboxylate based frameworks, and associated RhB photocatalytic degradation
      and 2D-IR COS tests.
AB  - Three alpha-Keggin heteropolymolybdates with the formula
      [(C(5)H(4)NH)COOH](3)[PMo(12)O(40)] 1,
      {[Sm(H(2)O)(4)(pdc)](3)}{[Sm(H(2)O)(3)(pdc)]}[SiMo(12)O(40)].3H(2)O 2 and
      {[La(H(2)O)(4)(pdc)](4)}[PMo(12)O(40)]F 3 (H(2)pdc = pyridine-2,6-dicarboxylate),
      have been synthesized under hydrothermal condition and characterized by single
      crystal X-ray diffraction analyses, elemental analyses, inductively coupled
      plasma atomic emission spectroscopy (ICP-AES), IR, thermal gravimetric analyses,
      thermal infrared spectrum analyses and powder X-ray diffraction (PXRD) analyses.
      Single crystal X-ray diffraction indicates all three compounds comprise ball
      shaped Keggin type [XMo(12)O(40)](n-) polyoxometalates (POMs) (n = 3, X = P; n =
      4, X = Si, respectively) with different types of carboxylic ligands derived from
      H(2)pdc, and these cluster anions are isostructural. In order to explore
      structural characteristics, Rhodamine B photocatalytic (RhB) degradation and two
      dimensional infrared correlation spectroscopy (2D-IR COS) tests, are investigated
      for 1, 2 and 3. In RhB degradation, all compounds show good photocatalytic
      activity. For 1, the activity mainly comes from POMs. While in 2 and 3, POMs'
      photocatalytic activity is enhanced by the Ln(iii)-pdc metal-organic frameworks.
      Structural properties like POM's stability and magnetic sensitivity are discussed
      by 2D-IR COS under thermal/magnetic perturbations.

PMID- 22623032
TI  - Creating dialogue, creating change through the arts.
AB  - The "wellness picnic," an interactive hands-on learning activity, was developed
      to engage people in reflective conversations about their health behaviors and
      wellness journey. Participants used pictures, colors, and words to transform a
      paper plate into a symbolic representation of what wellness looked like to them.
      Within the wisdom of each participant's paper plate drawing, there emerged
      pathways for living well, creating a respectful place for sharing wellness
      understandings and cancer risk reduction activities.

PMID- 22623033
TI  - Overexpression of RORgammat under control of the CD2 promoter induces polyclonal
      plasmacytosis and autoantibody production in transgenic mice.
AB  - Retinoic acid related orphan receptor gamma-t (RORgammat) is known to be a master
      regulator of Th17-cell development. In this study, we generated RORgammat
      overexpressing transgenic (RORgammat Tg) mice in which transgene expression was
      driven by the CD2 promoter, and found that these mice developed polyclonal
      plasmacytosis and autoantibody production. RORgammat Tg mice were generated on a
      C57BL/6 background, and also were intercrossed with BALB/c mice. BALB/c F1
      (BALB/F1) RORgammat Tg mice developed massive polyclonal plasma-cytosis, and had
      shorter life spans. Splenomegaly and infiltration of plasma cells into the lung
      were observed. Hyperglobulinemia, anti-double-stranded DNA antibodies, anti
      erythrocyte antibodies, and anti-platelet antibodies were detected in BALB/F1
      RORgammat Tg mice. In the present study, polyclonal plasmacytosis in BALB/F1
      RORgammat Tg mice appeared to be due to the induction of excessive IL-6
      production by IL-17. We detected increased numbers of CD11b(+)  cells that
      produced IL-6. We also generatedIL-6-deficient RORgammat Tg BALB/F1 background
      mice, which displayed high levels of serum IL-17, but did not develop severe
      hyperglobulinemia. Excessive IL-6 production by several cell types, including
      macrophages, in BALB/F1 RORgammat Tg mice, might effect the development of plasma
      cytosis. These results suggest that RORgammat plays important roles in the
      development of plasmacytosis and autoantibody production.

PMID- 22623034
TI  - Development and validation of a liquid chromatography-tandem mass spectrometry
      method for the determination of febuxostat in human plasma.
AB  - A rapid and sensitive analytical method based on liquid chromatography coupled to
      tandem mass spectrometry detection with positive ion electrospray ionization was
      developed for the determination of febuxostat in human plasma using d(7) 
      febuxostat as the internal standard (IS). A simple protein precipitation was
      performed using acetonitrile. The analyte and IS were subjected to
      chromatographic analysis on a Capcell PAK C(18) column (4.6 * 100 mm, 5 um) using
      acetonitrile-5 mm ammonium acetate-formic acid (85:15:0.015, v/v/v) as the mobile
      phase at a flow rate of 0.6 mL/min. An Agilent 6460 electrospray tandem mass
      spectrometer was operated in the multiple reaction monitoring mode. The precursor
      to-product ion transitions m/z 317 -> m/z 261 (febuxsotat) and m/z 324 -> m/z
      (261 + 262) (d(7) -febuxostat, IS) were used for quantitation. The results were
      linear over the studied range (10.0-5000 ng/mL), and the total analysis time for
      each chromatograph was 3 min. The intra- and inter-day precisions were less than
      7.9 and 7.2%, respectively, and the accuracy was within +/-4.2%. No evidence of
      analyte instability in human plasma was observed storage at -20 degrees C for 31
      days. This method was successfully applied in the determination of febuxostat
      concentrations in plasma samples from healthy Chinese volunteers.

PMID- 22623035
TI  - A mean-field approach to elastically coupled hair bundles.
AB  - We study the dynamics of oscillatory hair bundles which are coupled elastically
      in their deflection variable and are subject to noise. We present a stochastic
      description capturing the dynamics of the hair bundles' mean field. In
      particular, the presented derivation elucidates the origin of the previously
      described noise reduction by coupling. By comparison of simulations of the
      approximate dynamics and the full system, we verify our results. Furthermore, we
      demonstrate that the specific type of coupling considered implies coupling
      induced changes in the dynamics beyond mere noise reduction.

PMID- 22623036
TI  - Influence of environmental solution pH and microstructural parameters on
      mechanical behavior of amphoteric pH-sensitive hydrogels.
AB  - Amphoteric hydrogels contain both ionizable acidic and basic groups attached on
      the polymer chains, which can change their volume in response to the slight
      alteration of the surrounding environmental p H. In this paper, a theory of
      equilibrium swelling of amphoteric p H-sensitive hydrogels which is an extension
      of the formalism proposed by Marcombe et al. and a new hybrid free-energy density
      function of amphoteric hydrogels composed of the Edwards-Vilgis slip-link model
      and the Flory-Huggins solution theory as well as the contributions of mixing the
      mobile ions with the solvent, and dissociating the acidic and basic groups are
      presented for the prediction of the influence of environmental solution p H,
      microstructural parameters and geometric constraints on mechanical behavior. The
      calculations were modeled on chitosan-genipin gels, and the results were compared
      to experimental data. Numerical calculations show that the model is able to
      predict the dependence of swelling on p H and crosslinker qualitatively well and
      quantitatively close to the experimental data. Each gel shows minimal swelling at
      low p H but an increase in swelling until a maximum was reached; for most of the
      p H range, a good fit was achieved except for where the maximum swelling occurs;
      for experimental data, the maximum swelling appears at about pH = 4 , but for
      modeled data the maximum swelling appears between pH = 4 and pH = 6 ; each gel
      swell decreasing with increasing crosslinker concentration was also successfully
      predicted. The calculated results also show that microstructural parameters and
      geometric constraints have a significant impact on the mechanical behavior of the
      amphoteric hydrogels; the gel swells less when the network is more densely
      entangled and the maximum swelling ratio of the gels under biaxial constraint is
      only about one-third of the maximum when the gels swell freely. The theory
      developed here is valuable for the design and optimization of a drug delivery
      system.

PMID- 22623037
TI  - Segregation in arch formation.
AB  - We report new segregation phenomena in the clogging arches formed during the
      discharge of granular piles. Results from molecular dynamics simulations show
      segregation effects with respect to both size and density ratios used in piles
      built with bidisperse mixtures of grains. The clogging arch is preferentially
      constituted of large grains when size bidisperse piles were discharged, whereas
      for density bidisperse mixtures there is a predominance of light grains in the
      arch for large orifice widths but, for small widths, an inversion in the
      preference is observed, with a slightly higher incidence of heavy grains forming
      the arches. We present arguments based on the reverse buoyancy effect and the
      statistics collected for the avalanche size distributions to explain how these
      effects can be understood as a crossover between two different segregation
      mechanisms acting independently at small and large orifice width limits.

PMID- 22623038
TI  - Prognostic significance of VEGF at baseline in orbital retinoblastoma (IRSS stage
      II and stage III).

PMID- 22623039
TI  - [Cardiopulmonary Exercise Testing (CPET) in severe COPD--a multicentre comparison
      of two test protocols].
AB  - Cardiopulmonary exercise testing (CPET) allows a valid evaluation of
      cardiopulmonary function capability and the recognition of existing limitations
      in COPD patients. Whereas the measurement of the different parameters of CPET and
      the evaluation of the results are standardised, this does not apply to the
      protocols chosen. The aim of this study was to evaluate whether the results of
      two different exercise protocols were comparable in an outpatient multicentre
      setting. Ninety COPD patients stages II-IV according to the Gold classification
      were examined by means of symptom-limited exercise testing on a bicycle with two
      different ramp protocols (10 Watts vs. 16 Watts/min) within seven days. The
      results show that a higher acceleration rate of the load was associated with
      shorter exercise duration and higher achieved exercise capacity. Gas exchange and
      ventilatory parameters did not show significant differences on comparing both
      protocols. In pulmonary practices COPD patients of the Gold stages II-IV can be
      examined safely and with validity by means of CPET. The application of a ramp
      protocol with a stepwise increase of 16 Watts/minute can be recommended,
      particularly as for this regimen standardised normal values are available.

PMID- 22623040
TI  - ["Pinhead with tuberculosis pathogens"].

PMID- 22623041
TI  - Wing stents versus conventional plastic stents in the biliary tree: imagination
      in plastic biliary stent designs continues to evolve.

PMID- 22623042
TI  - Reduced diversity and imbalance of fecal microbiota in patients with ulcerative
      colitis.
AB  - BACKGROUND: Clinical observations and experimental colitis models have indicated
      the importance of intestinal bacteria in the etiology of ulcerative colitis (UC),
      but a causative bacterial agent has not been identified. AIM: To determine how
      intestinal bacteria are associated with UC, fecal microbiota and other components
      were compared for UC patients and healthy adults. METHODS: Fresh feces were
      collected from 48 UC patients. Fecal microbiota were analyzed by use of terminal
      restriction fragment length polymorphism (T-RFLP), real-time PCR, and culture.
      The concentrations of organic acids, indole, and ammonia, and pH and moisture,
      which are indicators of the intestinal environment, were measured and compared
      with healthy control data. RESULTS: T-RFLP data divided the UC patients into four
      clusters; one cluster was obtained for healthy subjects. The diversity of fecal
      microbiota was significantly lower in UC patients. There were significantly fewer
      Bacteroides and Clostridium subcluster XIVab, and the amount of Enterococcus was
      higher in UC patients than in healthy subjects. The fecal concentration of
      organic acids was significantly lower in UC patients who were in remission.
      CONCLUSION: UC patients have imbalances in the intestinal environment-less
      diversity of fecal microbiota, lower levels of major anaerobic bacteria
      (Bacteroides and Clostridium subcluster XIVab), and a lower concentration of
      organic acids.

PMID- 22623043
TI  - Deguelin, an Akt inhibitor, down-regulates NF-kappaB signaling and induces
      apoptosis in colon cancer cells and inhibits tumor growth in mice.
AB  - BACKGROUND: Deguelin, a naturally occurring rotenoid, is known to be an Akt
      inhibitor and to have an anti-tumor effect on several cancers. AIMS: This study
      was performed to elucidate the effect of deguelin on apoptotic pathways related
      to NF-kappaB signaling in colon cancer cells and on the anti-tumor effect in
      colon cancer xenograft mice. METHODS: We studied COLO 205 and HCT116 cells in the
      presence or absence of deguelin. NF-kappaB signaling was examined by real-time RT
      PCR for interleukin (IL)-8, by Western blotting for IkappaB
      phosphorylation/degradation, and by the electrophoretic mobility shift assay.
      Cell death was determined by the MTT assay, and apoptosis by Annexin V-FITC
      staining and caspase-3 activity. We also assessed the expression of antiapoptotic
      and proapoptotic factors by use of RT-PCR. In colon cancer xenograft mice, we
      evaluated the effect of deguelin on inoculated tumor growth, and apoptotic index
      was measured by the in vivo TUNEL assay. RESULTS: Deguelin significantly
      inhibited IL-8 gene expression, IkappaB phosphorylation/degradation, and DNA
      binding activity of NF-kappaB in colon cancer cells. Deguelin induced cell death
      and apoptosis in colon cancer cells in a dose and time-dependent manner. Deguelin
      down-regulated expression of NF-kappaB-mediated antiapoptotic factors such as
      cFLIP, Bcl-2, and Bcl-X(L). In the colon cancer xenograft model, the volume of
      the tumor treated with deguelin was significantly lower than that of the control,
      and the apoptotic index for deguelin-treated mice was much higher. CONCLUSION:
      Deguelin might be a potential therapeutic agent for treatment of colorectal
      cancer.

PMID- 22623044
TI  - Interaction of colistin and colistin methanesulfonate with liposomes: colloidal
      aspects and implications for formulation.
AB  - Interaction of colistin and colistin methanesulfonate (CMS) with liposomes has
      been studied with the view to understanding the limitations to the use of
      liposomes as a more effective delivery system for pulmonary inhalation of this
      important class of antibiotic. Thus, in this study, liposomes containing colistin
      or CMS were prepared and characterized with respect to colloidal behavior and
      drug encapsulation and release. Association of anionic CMS with liposomes induced
      negative charge on the particles. However, degradation of the CMS to form
      cationic colistin over time was directly correlated with charge reversal and
      particle aggregation. The rate of degradation of CMS was significantly more rapid
      when associated with the liposome bilayer than when compared with the same
      concentration in aqueous solution. Colistin liposomes carried positive charge and
      were stable. Encapsulation efficiency for colistin was approximately 50%,
      decreasing with increasing concentration of colistin. Colistin was rapidly
      released from liposomes on dilution. Although the studies indicate limited
      utility of colistin or CMS liposomes for long duration controlled-release
      applications, colistin liposomes were highly stable and may present a potential
      opportunity for coformulation of colistin with a second antibiotic to colocalize
      the two drugs after pulmonary delivery.

PMID- 22623045
TI  - [Resistance training for patients with cardiovascular diseases].
AB  - Physical training is part of the recommendations for prevention and
      rehabilitation of cardiovascular and metabolic diseases. The main focus was on
      endurance training for a long time. However, a positive effect of strength
      training has also been found for patients with with a wide spectrum of diseases.
      Beside the improvement of muscle strength similar positive effects as with
      endurance training have been documented. Moreover, improvements of quality of
      life and mobility have been found, mainly for older patients. Resistance training
      is safe and can be recommended to a wide range of patients including those with
      reduced left ventricular function.

PMID- 22623046
TI  - Teaching bioanalytical methods in a BSc analytical chemistry course.

PMID- 22623047
TI  - Pesticide residue analysis in cereal-based baby foods using multi-walled carbon
      nanotubes dispersive solid-phase extraction.
AB  - In the present study, a new analytical method has been developed for the
      simultaneous quantification of 15 organophosphorus pesticides, including some of
      their metabolites, (disulfoton-sulfoxide, ethoprophos, cadusafos, dimethoate,
      terbufos, disulfoton, chlorpyrifos-methyl, malaoxon, fenitrothion, pirimiphos
      methyl, malathion, chlorpyrifos, terbufos-sulfone, disulfoton-sulfone and
      fensulfothion) in three different types of commercial cereal-based baby foods.
      Dispersive solid-phase extraction (dSPE) with multi-walled carbon nanotubes
      (MWCNTs) was used together with gas chromatography with nitrogen phosphorus
      detection. Most favorable conditions involved a previous ultrasound-assisted
      extraction of the sample with acetonitrile containing formic acid. After
      evaporation of the extract and redissolution in water, a dSPE procedure was
      carried out with MWCNTs. The whole method was validated in terms of
      repeatability, linearity, precision and accuracy and matrix effect was also
      evaluated. Absolute recoveries were in the range 64-105 % with relative standard
      deviation values below 7.6 %. Limits of quantification achieved ranged from 0.31
      to 5.50 MUg/kg, which were lower than the European Union maximum residue limits
      for pesticide residues in cereal-based baby foods.

PMID- 22623048
TI  - Childhood asthma in low income countries: an invisible killer?
AB  - Bacterial pneumonia has hitherto been considered the key cause of the high
      respiratory morbidity and mortality in children under five years of age (under
      5s) in low-income countries, while asthma has not been stated as a significant
      reason. This paper explores the definitions and concepts of pneumonia and
      asthma/wheezing/bronchiolitis and examines whether asthma in under-5s may be
      confused with pneumonia. Over-diagnosing of bacterial pneumonia can be suspected
      from the limited association between clinical pneumonia and confirmatory test
      results such as chest x-ray and microbiological findings and poor treatment
      results using antibiotics. Moreover, children diagnosed with recurrent pneumonia
      in infancy were often later diagnosed with asthma. Recent studies showed a 10-15%
      prevalence of preschool asthma in low-income countries, although under-5s with
      long-term cough and difficulty breathing remain undiagnosed. New studies
      demonstrate that approximately 50% of acutely admitted under-5s diagnosed with
      pneumonia according to Integrated Management of Childhood Illnesses could be re
      diagnosed with asthma or wheezing when using re-defined diagnostic criteria and
      treatment. It is hypothesised that untreated asthma may contribute to respiratory
      mortality since respiratory syncytial virus (RSV) is an important cause of
      respiratory death in childhood, and asthma in under-5s is often exacerbated by
      viral infections, including RSV. Furthermore, acute respiratory treatment
      failures were predominantly seen in under-5s without fever, which suggests the
      diagnosis of asthma/wheezing rather than bacterial pneumonia. Ultimately,
      underlying asthma may have contributed to malnutrition and fatal bacterial
      pneumonia. In conclusion, preschool asthma in low-income countries may be
      significantly under-diagnosed and misdiagnosed as pneumonia, and may be the cause
      of much morbidity and mortality.

PMID- 22623049
TI  - Conflicting standards for diagnostic  spirometry within-session repeatability are
      confusing.

PMID- 22623050
TI  - Why do patients not attend communitybased  pulmonary rehabilitation, and how  can
      attendance be improved?

PMID- 22623051
TI  - The implementation of a COPD continuous management improvement programme:
      learning for the future.

PMID- 22623052
TI  - Effects of calcium salts of acidic monomers on mineral induction of
      phosphoprotein immobilized to agarose beads.
AB  - The aim of this study is to evaluate the mineralizing potential of acidic
      monomers and their calcium salts for mineralization, using an in vitro mineral
      induction model. Phosvitin (PV) was used as a model phosphoprotein in this study.
      PV was immobilized on agarose beads with divinyl sulfone. Five aliquots of
      agarose-immobilized PV, acidic monomers, and their calcium salts were incubated
      in mineralizing solution at various concentrations. The PV beads and acidic
      monomers were incubated at 37 degrees C. Samples were taken at several time
      points during the incubation. Then, the agarose beads were analyzed for bound
      calcium by atomic absorption spectrometry. The mineral formed on the agarose
      beads was identified as an apatite by microarea X-ray diffraction. Additionally,
      the specimens were observed using scanning electron microscopy (SEM). Mineral
      induction time decreased with increasing solution saturation. 4-METCa salt
      [calcium salt of 4-methacryloxyethyl trimellitate (CMET)] significantly reduced
      the mineral induction time. Using these data, the interfacial tension for mineral
      induction of PV and CMET was determined to be 90.1 and 92.7 ergs/cm(2),
      respectively. The mineral induced in each specimen after incubation for 24 h was
      identified by its X-ray diffraction pattern as apatite. SEM observation showed
      that lath-shaped crystals were formed on the surfaces of the CMET. We conclude
      that CMET could play a role in dentin remineralization.

PMID- 22623053
TI  - Toxicity of trifluralin herbicide in a representative of the edaphic fauna:
      histopathology of the midgut of Rhinocricus padbergi (Diplopoda).
AB  - The aim of this study was to use the diplopod Rhinocricus padbergi as test
      organism to verify the possible toxic effects of the herbicide trifluralin in a
      representative of the edaphic fauna. Histological and histochemical techniques
      were applied in the midgut of the animals after exposure to different
      concentrations of trifluralin for 7 and 90 days (acute and subchronic exposure,
      respectively). The individuals from the control group did not present alterations
      to any of the exposures. In the acute exposure, the group exposed to a quarter
      and half of the field dose presented an accumulation of cytoplasmic granules in
      the hepatic cells; the field dose group presented an increase in the rate of
      epithelial renewal and the group exposed to double the field concentration
      presented an increase in the release of secretory vesicles. The subchronic
      response was obtained with the field dose and double field dose because the
      animals from a quarter and half groups did not survive until the end of the
      experiment. In both groups, the animals presented disruption of the epithelium
      and higher occurrence of hemocytes among the hepatic cells. The group exposed to
      double the field dose presented sites of cytoplasmic vacuolization, dilatation of
      the intercellular space, increase in the epithelial renewal, and release of
      secretory vesicles. The results alert for a careful use of this herbicide, since
      it promoted alterations in the midgut cells of the test organism used.

PMID- 22623055
TI  - Treatment of relapsed/refractory germ cell tumours: an equipoise between
      conventional and high dose therapy.
AB  - OPINION STATEMENT: Patients with relapsed germ cell tumors (GCT) are potentially
      curable despite the failure of initial cisplatin based therapy. The recent
      identification of robust prognostic markers has helped clarify this area of
      uncertainty. However, unlike the initial treatment of metastatic disease where
      cisplatin based combination therapy is standard of care, there is no consensus on
      treatment in the relapsed setting. Instead there is a genuine equipoise between
      high dose therapy (HDCT) and conventional dose therapy (CDCT) in this relapsed
      setting. The randomised data fails to support the use of HDCT although
      retrospective analysis consistently shows it may be superior, especially if
      tandem or triple high dose therapy is used. This has resulted in different
      approaches worldwide with some stating HDCT should not be used outside of a trial
      and others suggesting it is standard of care. Re-challenging relapsed patients
      with conventional dose cisplatin based therapy would seem to be counterintuitive,
      but the addition of drugs such as ifosamide and paclitaxel results in genuine
      activated in selected patients with relapsed disease. This appears particularly
      relevant as HDCT is associated with significant morbidity and mortality, which
      was highlighted in a randomised trial. However large single institution data
      suggests this treatment related toxicity may not be such as concern and treatment
      related mortality can be as low as only 3 % in selected centres. Overall there is
      a need to answer this question of CDCT v.s. HSCT definitively. For this reason a
      prospective global randomised trial (TIGER trial) comparing conventional dose
      therapy (paclitaxel, ifosamide and cisplatin [TIP]) and triple high dose therapy
      (paclitaxel and ifosamide followed by high dose carboplatin and etoposide [TI
      CE]) is planned for 2012 (TIGER trial). Due to the rarity of this disease and
      complexities associated with a global trial, this study faces many challenges.
      Nevertheless it is hoped that it will finally address this area major of
      uncertainty in GCTs.

PMID- 22623056
TI  - Validation and application of a liquid chromatography-tandem mass spectrometric
      method for the determination of GDC-0152 in human plasma using solid-phase
      extraction.
AB  - A liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed
      and validated for the determination of GDC-0152 in human plasma to support
      clinical development. The method consisted of a solid-phase extraction for sample
      preparation and LC-MS/MS analysis in the positive ion mode using
      TurboIonSpray(TM) for analysis. d(7) -GDC-0152 was used as the internal standard.
      A linear regression (weighted 1/concentration(2) ) was used to fit calibration
      curves over the concentration range of 0.02-10.0 ng/mL for GDC-0152. There were
      no endogenous interference components in the blank human plasma tested. The
      accuracy at the lower limit of quantitation was 99.3% with a precision (%CV) of
      13.9%. For quality control samples at 0.0600, 2.00 and 8.00 ng/mL, the between
      run %CV was <=8.64. Between-run percentage accuracy ranged from 98.2 to 99.6%.
      GDC-0152 was stable in human plasma for 363 days at -20 degrees C and for 659
      days at -70 degrees C storage. GDC-0152 was stable in human plasma at room
      temperature for up to 25 h and through three freeze-thaw cycles. In whole blood,
      GDC-0152 was stable for 12 h at 4 degrees C and at ambient temperature. This
      validated LC-MS/MS method for determination of GDC-0152 was used to support
      clinical studies.

PMID- 22623057
TI  - Backbone 1H, 13C and 15N resonance assignments of dengue virus NS2B-NS3p in
      complex with aprotinin.
AB  - Dengue virus, belongs to Flaviviridae, is an arthropod transmitted virus that
      threatens millions of people's lives. As with other flaviviruses, a positive
      single-stranded 11-kilobases RNA in the dengue virus genome encodes three
      structural proteins (capsid protein C, membrane protein M, and envelope protein
      E) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5).
      The two component protease NS2B-NS3p is essential for viral replication and is
      believed to be a potential antiviral drug target. Aprotinin, a native inhibitor,
      is proved to retard the activity of NS2B-NS3p. The backbone assignments of NS2B
      NS3p will be essential for determining the high resolution solution structure of
      NS2B-NS3p and screening new antiviral drugs. Herein, we report the backbone (1)H,
      (15)N, (13)C resonance assignments of the N terminal fragment of NS2B (4.8 kDa)
      and NS3p (18.5 kDa) in complex with aprotinin (6.5 kDa) by high resolution NMR.

PMID- 22623058
TI  - ZnO/liquid crystalline nanohybrids: from properties in solution to anisotropic
      growth.
AB  - Branched thermotropic liquid crystals (LCs) were successfully used as stabilizers
      for the synthesis of isotropic photoluminescent ZnO nanoparticles (NPs) in
      solution. (1)H NMR spectroscopy and differential scanning calorimetry experiments
      demonstrate the existence of specific interactions between the LC and both the
      ZnO precursor and ZnO NPs. This offers the possibility for some branched
      molecules to act as structurally ordered hosts for the anisotropic growth of ZnO
      NPs.

PMID- 22623059
TI  - [Qualification guideline of the German Roentgen Society and the German Society of
      Interventional Radiology and Minimal Invasive Therapy for performing
      interventional radiologic minimal invasive procedures on arteries and veins].

PMID- 22623060
TI  - Optimized selection of unrelated subjects for whole-genome sequencing studies of
      rare high-penetrance alleles.
AB  - Sequencing studies using whole-genome or exome scans are still more expensive
      than genome-wide association studies on a per-subject basis. As a result, only a
      subset of subjects from a larger study will be selected for sequencing. To
      perform an agnostic investigation of the entire genome, subjects may be selected
      that capture independent ancestral lineages, i.e., founder genomes, and thus
      avoid redundant information from regions that were inherited identical by descent
      (IBD) from a common ancestor. We present SampleSeq2 that can be used to select a
      subset of optimally unrelated subjects with minimal IBD sharing. It also can be
      used to estimate the number, G(T), of founder chromosomes in a sample or select
      the minimum number of subjects that will carry a target G(T). We evaluated
      SampleSeq2 compared to a random draw of a small number of subjects both by
      simulation and using the Anabaptist genealogy. SampleSeq2 provided an increase in
      G(T) relative to a random draw across a range of small sample sizes. This
      increase in founder chromosomes improves the power of association tests,
      mitigates the effect of cryptic relatedness on parameter estimates, increases the
      total yield of alleles from sequencing, and minimizes the average size of regions
      shared IBD around disease alleles in cases.

PMID- 22623061
TI  - Lower TGFbeta serum levels and higher frequency of IFNgamma-producing T cells
      during early immune reconstitution in surviving children after allogeneic stem
      cell transplantation.
AB  - BACKGROUND: Allogeneic hematopoietic stem cell transplantation (SCT) is
      increasingly used as a salvage therapy for patients with high-risk malignancies
      as well as life-threatening non-malignant diseases. However, only limited data
      about the association between outcome and functional parameters of recovering
      lymphocytes are available so far. PROCEDURES: In this prospective study of 19
      pediatric SCT recipients, we serially evaluated immune parameters quantitatively
      and qualitatively before and throughout allogeneic SCT. These data were analyzed
      with respect to survival. RESULTS: Age, gender, GvHD, and type of graft were not
      different between surviving and non-surviving patients. Notably, in our cohort
      there was no case of transplant-related or infectious mortality. However, with
      the exception of two patients with advanced MDS, all patients not in complete
      remission (CR) relapsed in addition to three patients in higher CR (n = 7). All
      seven patients relapsing after allogeneic SCT later succumbed to their disease
      recurrence. Uni- and multivariate analysis showed that relapsing patients had
      higher TGFbeta serum levels as well as lower percentages of IFNgamma-producing T
      cells before and early after transplantation. Furthermore, relapsing patients had
      a further decline in their thymic function between day 60 and 120 whereas non
      relapsing patients already showed increasing TREC values during this time
      interval. CONCLUSIONS: Collectively, patients who later relapse show a different
      pattern of immune reconstitution before and at early time points post
      transplantation.

PMID- 22623062
TI  - Total hip arthroplasty versus hemiarthroplasty for displaced femoral neck
      fractures in the healthy elderly: a meta-analysis and systematic review of
      randomized trials.
AB  - PURPOSE: Displaced femoral neck fractures in healthy elderly patients have
      traditionally been managed with hemiarthroplasty (HA). Recent data suggest that
      total hip arthroplasty (THA) may be a better alternative. METHODS: A systematic
      review of the English literature was conducted. Randomized controlled trials
      comparing all forms of THA with HA were included. Three authors independently
      extracted articles and predefined data. Results were pooled using a random
      effects model. RESULTS: Eight trials totalling 986 patients were retrieved. After
      THA 4 % underwent revision surgery versus 7 % after HA. The one-year mortality
      was equal in both groups: 13 % (THA) versus 15 % (HA). Dislocation rates were 9 %
      after THA versus 3 % after HA. Equal rates were found for major (25 % in THA
      versus 24 % in HA) and minor complications (13 % THA versus 14 % HA). The
      weighted mean of the Harris hip score was 81 points after THA versus 77 after HA.
      The subdomain pain of the HHS (weighted mean score after THA was 42 versus 39
      points for HA), the rate of patients reporting mild to no pain (75 % after THA
      versus 56 % after HA) and the score of WOMAC (94 points for THA versus 78 for HA)
      all favored THA. Quality of life measured with the EQ-5D favored THA (0.69 versus
      0.57). CONCLUSIONS: Total hip arthroplasty for displaced femoral neck fractures
      in the fit elderly may lead to higher patient-based outcomes but has higher
      dislocation rates compared with hemiarthroplasty. Further high-quality randomized
      clinical trails are needed to provide robust evidence and to definitively answer
      this clinical question.

PMID- 22623063
TI  - An extra-articular procedure improves the clinical outcome in anterior cruciate
      ligament reconstruction with hamstrings in female athletes.
AB  - PURPOSE: A positive glide is a common finding after ACL reconstructions,
      especially in women. The aim of this study was to prospectively evaluate the role
      of Cocker-Arnold's extra-articular procedure in reducing the incidence of a
      residual postoperative rotational knee laxity. METHODS: Sixty patients affected
      by an ACL injury with a +2 (clunk) or +3 (gross shift) pivot-shift test entered
      this prospective study; they were randomly assigned to group A (control group,
      hamstrings) or group B (study group, hamstrings plus Cocker-Arnold). Thirty-two
      patients entered group A and 28 group B. At follow-up, patients underwent
      clinical evaluation, KT-1000 arthrometer and Lysholm, Tegner, VAS and subjective
      and objective IKDC form. RESULTS: At a mean follow-up of 44.6 months, the same
      expert surgeon reviewed 55 patients (28 group A and 27 group B). The comparison
      of the results of the evaluation scales used and of the KT-1000 arthrometer did
      not show statistically significant differences (p>0.05). Lachman test was
      negative (S/S) in all the patients of both groups (100 %). A residual positive
      pivot-shift (glide) was found in 16 patients (57.1 %) of group A and in five
      patients (18.6 %) of group B (p<0.05). CONCLUSIONS: The extra-articular MacIntosh
      procedure modified by Cocker-Arnold in combination with ACL reconstruction
      significantly reduces the rotational instability of the knee.

PMID- 22623064
TI  - Is the expression of Transforming Growth Factor-Beta1 after fracture of long
      bones solely influenced by the healing process?
AB  - PURPOSE: Circulating TGF-beta1 levels were found to be a predictor of delayed
      bone healing and non-union. We therefore aimed to investigate some factors that
      can influence the expression of TGF-beta1. The correlation between the expression
      of TGF-beta1 and the different socio-demographic parameters was analysed.
      METHODS: Fifty-one patients with long bone fractures were included in the study
      and divided into different groups according to their age, gender, cigarette
      smoking status, diabetes mellitus and regular alcohol intake. TGF-beta1 levels
      were analysed in patient's serum and different groups were retrospectively
      compared. RESULTS: Significantly lower TFG-beta1 serum concentrations were
      observed in non-smokers compared to smokers at week 8 after surgery.
      Significantly higher concentrations were found in male patients compared to
      females at week 24. Younger patients had significantly higher concentrations at
      week 24 after surgery compared to older patients. Concentrations were
      significantly higher in patients without diabetes compared to those with diabetes
      at six weeks after surgery. Patients with chronic alcohol abuse had significantly
      higher concentrations compared to those patients without chronic alcohol abuse.
      CONCLUSION: TGF-beta1 serum concentrations vary depending upon smoking status,
      age, gender, diabetes mellitus and chronic alcohol abuse at different times and
      therefore do not seem to be a reliable predictive marker as a single-point-in
      time measurement for fracture healing.

PMID- 22623065
TI  - Accumulation of cyclophilin A isoforms in conditioned medium of irradiated breast
      cancer cells.
AB  - Secreted proteins play a key role in cell signaling and communication. We
      recently showed that ionizing radiations induced a delayed cell death of breast
      cancer cells, mediated by the death receptor pathways through the expression of
      soluble forms of "death ligands." Using the same cell model, the objective of our
      work was the identification of diffusible factors, secreted following cell
      irradiation, potentially involved in cell death signaling. Differential proteomic
      analysis of conditioned media using 2DE resulted in detection of numerous spots
      that were significantly modulated following cell irradiation. The corresponding
      proteins were identified using MALDI-TOF MS and LC-MS/MS approaches.
      Interestingly, five isoforms of cyclophilin A were observed as increased in
      conditioned medium of irradiated cells. These isoforms differed in isoelectric
      points and in accumulation levels. An increase of cyclophilin A secretion was
      confirmed by Western blotting of conditioned media of irradiated or radiosentive
      mammary cells. These isoforms displayed an interesting pattern of protein
      maturation and post-translational modifications, including an alternating removal
      of N-terminal methionine, associated with a combination of acetylations and
      methylations. The role of the protein is discussed in relation with its potential
      involvement in the mechanisms of intercells relationships and radiosensitivity.

PMID- 22623066
TI  - A phase I study of S-1 with concurrent radiotherapy in elderly patients with
      locally advanced non-small cell lung cancer.
AB  - BACKGROUND: A phase I study was performed to evaluate dose-limiting toxicity and
      the recommended dose for the oral fluoropyrimidine S-1 administered concurrently
      with thoracic radiotherapy (TRT) in elderly (>= 70 years of age) patients with
      locally advanced non-small cell lung cancer. METHODS: S-1 was administered on
      days 1 to 14 and 22 to 35 at oral doses of 65 or 80 mg m(-2) day(-1). TRT was
      administered in 2-Gy fractions five times weekly for a total dose of 60 Gy.
      Twelve previously untreated patients were treated with S-1 at 65 (n=6) or 80
      (n=6) mg m(-2) day(-1). RESULTS: All patients completed the planned 60 Gy of TRT.
      Dose-limiting toxicity included pneumonitis (n=2), infection (n=1), and
      stomatitis (n=1), each of grade 3, but each event was reversible. The recommended
      dose for S-1 was determined to be 80 mg m(-2) day(-1). No patient experienced
      toxicity of grade 4. The dose intensity of S-1 was well maintained and the
      combination of S-1 plus TRT was well tolerated overall. The overall response rate
      was 83.3 %, with a median survival time of 34.0 months. CONCLUSIONS:
      Administration of S-1 at 80 mg m(-2) day(-1) on days 1 to 14 and 22 to 35 can be
      safely combined with concurrent TRT in elderly patients with locally advanced non
      small cell lung cancer.

PMID- 22623068
TI  - Complementary methods provide evidence for the expression of CXCR7 on human B
      cells.
AB  - PTMs of extracellular domains of membrane proteins can influence antibody binding
      and give rise to ambivalent results. Best proof of protein expression is the use
      of complementary methods to provide unequivocal evidence. CXCR7, a member of the
      atypical chemokine receptor family, mainly functions as scavenger for the
      chemokines CXCL12 and CXCL11. The expression of CXCR7 on nonhematopoietic cells
      and neoplasms is widely accepted, however, its expression on leukocytes was
      recently challenged. To solve the dissent, we thoroughly analyzed the expression
      of CXCR7 on human B cells. We validated the efficiency of different epitope
      specific monoclonal antibodies to detect CXCR7 on transfected cells and primary
      human B cells. The specificity of the used antibodies was further confirmed by an
      experimentally independent double labeling approach. Examination of CXCR7
      dependent scavenging of fluorescent-labeled CXCL12 revealed functional expression
      of the receptor on human B cells. Moreover, real-time PCR analysis of CXCR7 mRNA
      showed the presence of transcripts in human leukocytes. Finally, two CXCR7
      specific peptides were identified by MS in immunoprecipitates from primary human
      B cells. Thus, we present a strategy based on combined proteomic and functional
      approaches that can be used to solve dissents on protein expression, i.e.
      demonstrating the expression of CXCR7 on human leukocytes.

PMID- 22623067
TI  - Biological characterization of ETP-46321 a selective and efficacious inhibitor of
      phosphoinositide-3-kinases.
AB  - Inhibitors of PI3K signaling are of great therapeutic interest in oncology. The
      phosphoinositide-3-kinase signaling pathway is activated in a variety of solid
      and non-solid tumors. We have identified an imidazopyrazine derivative, ETP
      46321, as a potent inhibitor of PI3Kalpha [Formula: see text]. The compound was 6
      times less potent towards PI3Kdelta and more than 200 and 60 times less potent at
      inhibiting PI3Kbeta and PI3Kgamma and did not significantly inhibit the related
      phosphoinositide-3-kinase-related protein kinase family kinases mTOR or DNA PK
      (IC(50)'s > 5 MUM), or an additional 287 protein kinases that were screened. ETP
      46321 inhibited PI3K signaling in treated tumor cell lines, induced cell cycle
      arrest and inhibited VEGF-dependent sprouting of HUVEC cells. The compound was
      anti-proliferative and synergized with both cytotoxic and targeted therapeutics.
      The compound induced a reduction in the phosphorylation of Akt in U87 MG
      xenografts after a single treatment. The growth of colon and lung cancinoma HT-29
      and A549 xenografts was delayed by once a day treatment with ETP-46321. The
      compound synergized with Doxotaxel in a model of ovarian cancer.

PMID- 22623069
TI  - Dietary supplement use is not associated with recurrence of colorectal adenomas:
      a prospective cohort study.
AB  - Diet and lifestyle influence colorectal adenoma recurrence. The role of dietary
      supplement use in colorectal adenoma recurrence remains controversial. In this
      prospective cohort study, we examined the association between dietary supplement
      use, total colorectal adenoma recurrence and advanced adenoma recurrence.
      Colorectal adenoma cases (n = 565) from a former case-control study, recruited
      between 1995 and 2002, were prospectively followed until 2008. Adenomas with a
      diameter of >=1 cm and/or (tubulo)villous histology and/or with high grade
      dysplasia and/or >=3 adenomas detected at the same colonic examination were
      considered advanced adenomas. Hazard ratios (HRs) and 95% confidence intervals
      (CIs) for dietary supplement users (use of any supplement during the past year)
      compared to nonusers and colorectal adenoma recurrence were calculated using
      stratified Cox proportional hazard models for counting processes and were
      adjusted for age, sex, educational level and number of colonoscopies during
      follow-up. Robust sandwich covariance estimation was used to adjust for the
      within subject correlation. A number of 165 out of 565 adenoma patients had at
      least one colorectal adenoma recurrence during a median person-time of 5.4 years
      and of these, 37 patients had at least one advanced adenoma. One-third of the
      total study population (n = 203) used a dietary supplement. Compared to no use,
      dietary supplement use was neither statistically significantly associated with
      total colorectal adenoma recurrence (HR = 1.03; 95% CI 0.79-1.34) nor with
      recurrent advanced adenomas (HR = 1.59; 95% CI 0.88-2.87). This prospective
      cohort study did not suggest an association between dietary supplement use and
      colorectal adenoma recurrence.

PMID- 22623071
TI  - Nuclear p63 expression in osteoblastic tumors.
AB  - Expression of the p63 tumor suppressor protein has been reported in the
      mononuclear stromal cells of giant cell tumor of the bone, which may represent
      osteoblast-precursor cells. Only a limited number of osteoblastic tumors have
      been studied for p63 expression thus far. We therefore examined whether p63 may
      serve as a marker for osteoblastic differentiation in osteosarcomas or as a
      differential diagnostic marker to distinguish osteoblastoma from osteosarcoma.
      Immunohistochemical stains for p63 were performed on a tissue microarray
      containing 71 chemotherapy naive biopsy samples of osteosarcoma, 21 whole
      sections of osteosarcoma, and 8 osteoblastomas. Nuclear p63 was detected in seven
      of eight osteoblastomas but was restricted to stromal cells within primitive,
      immature-appearing areas of osteoid deposition. Although only 7 of 71 (10 %)
      biopsy samples of osteosarcoma represented on the tissue microarray were positive
      for p63, 7 of 21 (33 %) osteosarcomas were positive when whole tissue sections
      were evaluated. Although p63 is detected in most osteoblastomas, it is also
      observed in a significant subset of osteosarcomas, severely limiting its utility
      in distinguishing between benign and malignant osteoblastic tumors. The
      relatively low prevalence of p63 expression in osteosarcoma would also seem to
      preclude its use as a marker of osteoblastic differentiation in skeletal
      sarcomas.

PMID- 22623072
TI  - New-onset migraine with aura after transcatheter closure of atrial septal defect.
AB  - Transcatheter closure of atrial septal defect (ASD) is associated with a high
      success rate and become an accepted alternative to surgical treatment. We
      describe here a case of a 35-year-old woman who presented with migraine attacks
      with aura after transcatheter closure of ASD with an Amplatzer septal occluder
      device. We postulate that any of the following may have been responsible for her
      condition: platelet activation on the surface of the device, nickel allergy, or
      the release of the atrial natriuretic peptide associated with the stretch of the
      atrial septum caused by the device. This case demonstrates that de novo migraine
      can occur after transcatheter closure of ASD and should be recognized as a
      potential complication.

PMID- 22623073
TI  - Cutaneous innervation and trigeminal pathway function in a patient with facial
      pain associated with Parry-Romberg syndrome.
AB  - Parry-Romberg syndrome (PRS) is a rare condition manifesting with progressive
      hemifacial atrophy. Although reported PRS clinical disturbances include facial
      pain and recent studies raised the possibility that PRS-related pain is a
      neuropathic pain condition due to the trigeminal nerve damage, no studies have
      directly investigated cutaneous innervation and trigeminal pathway function in
      patients with this rare condition. In a 50-year-old woman presenting with a 10
      year history of slowly progressive hemifacial atrophy and facial pain, we
      investigated large myelinated fibres with masticatory muscle electromyography and
      trigeminal reflexes, and tested small myelinated and unmyelinated fibres with
      laser-evoked potentials. We also investigated cutaneous innervation by measuring
      the intraepidermal nerve fibre (IENF) density after skin biopsy of the
      supraorbital regions. We found that neurophysiological data and IENF density came
      within normal ranges, with no differences between normal and affected side. Our
      study showing that the standard reference techniques for assessing cutaneous
      innervation and trigeminal pathway function disclosed no abnormalities in this
      patient with PRS suggest that this rare and disabling condition is not associated
      with trigeminal system damage. These findings indicate that in this patient PRS
      related pain is not a neuropathic pain condition, rather it probably arises from
      the musculoskeletal abnormalities.

PMID- 22623074
TI  - Photodegradation of oxytocin and thermal stability of photoproducts.
AB  - Photodegradation of oxytocin at lambda = 253.7 nm and lambda >= 290 nm results in
      the transformation of the intrachain disulfide bond into predominantly
      dithiohemiacetal and thioether. Especially the dithiohemiacetal is sensitive to
      further degradation by light and/or elevated temperature, implying that the
      combination of an initial photostress and a subsequent heat stress can yield
      products significantly different compared with those observed under heat stress
      only.

PMID- 22623075
TI  - The efficacy of a thrombin-based hemostatic agent in unilateral total knee
      arthroplasty: a randomized controlled trial.
AB  - INTRODUCTION: Blood loss following total knee arthroplasty can lead to
      substantial morbidity and the need for blood transfusions. Hemostatic agents have
      been used to minimize blood loss and to decrease transfusion rates. Floseal is a
      thrombin-based hemostatic agent with unknown efficacy for achieving these goals
      in patients undergoing total knee arthroplasty. METHODS: We performed a
      prospective randomized controlled trial on the use of Floseal in patients
      undergoing total knee arthroplasty, with the primary end point being blood loss
      as measured through drain output. Demographic characteristics, operative side,
      diagnosis, intraoperative details, implant choice, hospital course, laboratory
      values, visual analog scale pain scores, knee range of motion, adverse events,
      transfusion rates, and deviations from protocol were recorded. RESULTS: A total
      of 196 patients were enrolled, with ninety-seven patients being randomized to the
      Floseal group and ninety-nine patients being randomized to the control group.
      There were no significant differences between the Floseal and control groups in
      terms of drain output at twenty-four hours (711 compared with 702 mL; p = 0.823).
      No differences were noted between the groups in terms of operative side,
      diagnosis, intraoperative details, implant choice, hospital course, laboratory
      values, visual analog scale pain scores, knee range of motion, or transfusion
      rates. Complications occurred infrequently. In the acute postoperative period,
      there were two cases of cellulitis (one in each group), two deep venous
      thromboses (one in each group), and one paralytic ileus (in the control group),
      all of which resolved with nonoperative measures. At the six-week follow-up, one
      patient in the Floseal group had died from a cause unrelated to surgery, two
      patients (one in each group) had suture abscesses with cellulitis that resolved
      with postoperative antibiotics, and four patients (two in each group) underwent
      knee manipulation under anesthesia to achieve improved knee motion. With the
      numbers available, there was no significant association between Floseal use and
      the occurrence of these adverse events. CONCLUSIONS: The present study showed
      that Floseal had no demonstrable effect on blood loss as measured through drain
      output following total knee arthroplasty. There were also no notable adverse
      events associated with its use. The usefulness of Floseal as a hemostatic agent
      in total knee arthroplasty remains unclear.

PMID- 22623077
TI  - Influence of multilayer rhBMP-2 DNA coating on the proliferation and
      differentiation of MC3T3-E1 cells seeded on roughed titanium surface.
AB  - For bone morphogenetic protein (BMP) gene therapy to be a viable approach for
      enhancing implant osseointegration clinically, requires the development of
      efficient nonviral delivery vectors that can coat the implant. This study
      evaluated a multilayer cationic liposome-DNA complex (LDc) coating as a delivery
      vehicle for recombinant human BMP-2 (rhBMP-2). Multilayered coatings, comprising
      hyaluronic acid (HA) and LDc, were fabricated onto titanium using a layer-by
      layer (LBL) assembly technique. Preosteoblastic MC3T3-E1 cells were cultured on
      the roughened titanium surfaces coated with multilayers of HA/LDc, or on uncoated
      or HA/liposome only surfaces as controls. The amount of rhBMP-2 secreted by the
      MC3T3-E1 cells and the effect of the various surfaces on cell viability,
      proliferation, alkaline phosphatase (ALP) activity, osteocalcin (OC) secretion,
      and calcium deposition were evaluated. Messenger RNA levels of OC, ALP, Runx2,
      and Osx were also investigated. The results demonstrated that rhBMP-2 protein
      secreted into culture medium at 3 days was significantly higher than control
      groups. MC3T3-E1 cells cultured on the HA/LDc coating displayed significantly
      higher ALP activity and OC secretion at 7 days and 14 days culture, respectively.
      MC3T3-E1 cells cultured on HA/LDc upregulated expression of the osteoblast
      differentiation markers, especially on days 12 for OC and on days 6 and 12 for
      ALP and Osx. In conclusion, MC3T3-E1 cell cultured on the multilayer HA/LDc
      coating surface can secret rhBMP-2 protein and the protein levels were effective
      in inducing early osteogenic differentiation.

PMID- 22623079
TI  - Luminescence properties of C-diazaborolyl-ortho-carboranes as donor-acceptor
      systems.
AB  - Seven derivatives of 1,2-dicarbadodecaborane (ortho-carborane, 1,2
      C(2)B(10)H(12)) with a 1,3-diethyl- or 1,3-diphenyl-1,3,2-benzodiazaborolyl group
      on one cage carbon atom were synthesized and structurally characterized. Six of
      these compounds showed remarkable low-energy fluorescence emissions with large
      Stokes shifts of 15100-20260 cm(-1) and quantum yields (Phi(F)) of up to 65% in
      the solid state. The low-energy fluorescence emission, which was assigned to a
      charge-transfer (CT) transition between the cage and the heterocyclic unit,
      depended on the orientation (torsion angle, psi) of the diazaborolyl group with
      respect to the cage C-C bond. In cyclohexane, two compounds exhibited very weak
      dual fluorescence emissions with Stokes shifts of 15660-18090 cm(-1) for the CT
      bands and 1960-5540 cm(-1) for the high-energy bands, which were assigned to
      local transitions within the benzodiazaborole units (local excitation, LE),
      whereas four compounds showed only CT bands with Phi(F) values between 8-32%. Two
      distinct excited singlet-state (S(1)) geometries, denoted S(1)(LE) and S(1)(CT),
      were observed computationally for the benzodiazaborolyl-ortho-carboranes, the
      population of which depended on their orientation (psi). TD-DFT calculations on
      these excited state geometries were in accord with their CT and LE emissions.
      These C-diazaborolyl-ortho-carboranes were viewed as donor-acceptor systems with
      the diazaborolyl group as the donor and the ortho-carboranyl group as the
      acceptor.

PMID- 22623078
TI  - Systematic review: The role of race and socioeconomic factors on IBD healthcare
      delivery and effectiveness.
AB  - BACKGROUND: Race and socioeconomic status (SES) significantly affect the content
      and delivery of healthcare for multiple chronic disease states. Inflammatory
      bowel disease (IBD) is a set of complex, chronic diseases with the potential for
      significant morbidity if the content or delivery of healthcare is suboptimal.
      However, the literature related to race, SES, and IBD remains fragmented.
      METHODS: Using guidelines published by the Centre for Reviews and Dissemination,
      we performed a systematic review of the world's literature to identify studies
      related to: 1) IBD, 2) race/ethnicity, 3) SES, 4) healthcare delivery, and 5)
      healthcare effectiveness. RESULTS: We identified 40 studies that met inclusion
      criteria. Twenty-four studies (60%) assessed the role of SES and 21 (53%)
      evaluated race. Topics addressed by these studies included: 1) Utilization of
      Medical and Surgical Therapy; 2) Adherence to Medical Therapy; 3) Clinical
      Outcomes; 4) Healthcare Access and Utilization; 5) Disease Perception and
      Knowledge; and 6) Employment/Insurance. We identified race- and SES-based
      disparities in the content of medical and surgical healthcare, utilization of
      inpatient and ambulatory medical care, adherence to medical therapy, and disease
      perceptions and knowledge. Several studies also identified race- and SES-based
      disparities in outcomes for IBD, including in-hospital mortality rates and health
      related quality of life. CONCLUSIONS: Race- and SES-based disparities in the
      delivery and effectiveness of healthcare for patients with IBD exist in numerous
      domains, yet studies remain limited in their scope and breadth. Concerted,
      prospective, multicenter efforts are needed to address underlying causes for
      disparities and to identify methods of reducing and eliminating disparities.

PMID- 22623080
TI  - Ketofol in electroconvulsive therapy anesthesia: two stones for one bird.
AB  - PURPOSE: Propofol and ketamine have become progressively popular in
      electroconvulsive therapy (ECT) anesthesia, although propofol shortened seizure
      duration and ketamine might cause cardiotoxicity, psychotic episodes, and delayed
      recovery. Ketofol is a combination of ketamine and propofol, and the current
      study was designed to evaluate the effect of ketamine, propofol, and ketofol on
      hemodynamic profile, duration of seizure activity, and recovery times in patients
      undergoing ECT. METHODS: Ninety patients (44 women, mean age 27.8 +/- 7.2 years)
      in one ECT session were enrolled and randomized to the propofol, ketamine, or
      ketofol group. Hemodynamic profile duration of seizure activity and recovery
      times were recorded. RESULTS: Motor seizure duration in the propofol group was
      significantly decreased compared to other groups (p < 0.001), whereas spontaneous
      breathing time in the ketamine group statistically increased compared to the
      propofol group (p = 0.001), and also eye-opening time (p < 0.001) and obeying
      command time (p < 0.001) was significantly increased in the ketamine group
      compared to other groups. Heart rate (HR) at induction (ketamine 91.2 +/- 13.6
      vs. propofol 77 +/- 13.4 and ketofol 79.9 +/- 15.6; p < 0.013; p < 0.08,
      respectively) was statistically significantly increased in the ketamine group
      compared to other groups, and HR at the third minute (ketamine 92 +/- 12.9 vs.
      propofol 79.4 +/- 9.3 and ketofol 81.5 +/- 14.2; p < 0.012, p < 0.048) was also
      statistically significantly increased in ketamine group compared to other groups.
      CONCLUSION: The ketofol 1:1 mixture is associated with longer mean seizure time
      than propofol, and shorter mean recovery times than ketamine, with better
      hemodynamic stability, without any important side effects in ECT anesthesia.

PMID- 22623081
TI  - Immunoproteomic identification of biotransformed self-proteins from the livers of
      female Balb/c mice following chronic ethanol administration.
AB  - Chronic alcohol consumption culminates in alcoholic hepatitis which is
      characterized by ballooning degeneration of hepatocytes and perivenous
      inflammation. The aldehydes produced by ethanol oxidation and lipid peroxidation
      form adducts with the hepatic proteins rendering them immunogenic and initiating
      an autoimmune response. The present study was designed to identify these
      immunoreactive hepatic proteins in ethanol-treated Balb/c mice. Liver cytosolic,
      mitochondrial, and microsomal proteins from the ethanol-treated and control
      female Balb/c mice were size fractionated on SDS-PAGE and immunoblotted with the
      sera from the individual animal. The immunoreactive proteins were identified
      using antimouse IgG antibody and characterized by MALDI-TOF. It is the first
      report demonstrating that 15 hepatic proteins show immunoreactivity following
      alcohol administration. The identified autoreactive proteins ranged in function
      from metabolism to cytoskeletal support. Remarkably, three key enzymes of ethanol
      metabolism, namely alcohol dehydrogenase, aldehyde dehydrogenase I and III as
      well as important antioxidant enzyme glutathione S-transferase were found to be
      autoreactive upon ethanol treatment. We conclude that ethanol treatment induces
      biotransformation of host proteins from almost every compartment of the cell,
      especially the enzymes involved in the detoxification of ethanolic insult being
      the major target for biotransformation. Hence, we propose that these proteins can
      be the potential candidates for the biomarker studies.

PMID- 22623082
TI  - Development and validation of LC-MS/MS method for the estimation of beta-hydroxy
      beta-methylbutyrate in rat plasma and its application to pharmacokinetic studies.
AB  - A simple, sensitive and specific high-performance liquid chromatography mass
      spectrometry (LC-MS/MS) method was developed and validated for the quantification
      of beta-hydroxy-beta-methyl butyrate (HMB) in small volumes of rat plasma using
      warfarin as an internal standard (IS). The API-4000 LC-MS/MS was operated under
      the multiple reaction-monitoring mode using the electrospray ionization
      technique. A simple liquid-liquid extraction process was used to extract HMB and
      IS from rat plasma. The total run time was 3 min and the elution of HMB and IS
      occurred at 1.48 and 1.75 min respectively; this was achieved with a mobile phase
      consisting of 0.1% formic acid in a water-acetonitrile mixture (15:85, v/v) at a
      flow rate of 1.0 mL/min on a Agilent Eclipse XDB C(8) (150 * 4.6, 5 um) column.
      The developed method was validated in rat plasma with a lower limit of
      quantitation of 30.0 ng/mL for HMB. A linear response function was established
      for the range of concentrations 30-4600 ng/mL (r > 0.998) for HMB. The intra- and
      inter-day precision values for HMB were acceptable as per Food and Drug
      Administration guidelines. HMB was stable in the battery of stability studies,
      viz. bench-top, autosampler freeze-thaw cycles and long-term stability for 30
      days in plasma. The developed assay method was applied to a bioavailability study
      in rats.

PMID- 22623083
TI  - Intraoral phaeohyphomycosis.
AB  - Phaeohyphomycosis is an infection caused by pigment-producing saprophytic fungi.
      Systemic infections may occur in the immunocompromised patient. Infection in
      healthy individuals may result in subcutaneous abscess formation. Oral lesions
      appear to be rare. A case of intraoral phaeohyphomycosis presenting as a well
      demarcated, painful nodule of the anterior hard palate in a 12-year-old healthy
      male is described. The mass was excised and the diagnosis was established
      following histopathologic examination of the tissue.

PMID- 22623084
TI  - Osteochondrolipoma of the submandibular region: a case report and review of the
      literature.
AB  - Lipoma is an extremely common and ubiquitous benign soft tissue tumor composed of
      mature adipose tissue, with frequent differentiation towards other mesenchymal
      elements such as blood vessels, fibrous tissue, or muscle. They are typically
      slow-growing, encapsulated, superficial or deep, and have a wide range in size
      depending on their location. The presence of cartilage or bone is very rare, with
      most reported cases in the head and neck area. We report the case of an
      osteochondrolipoma of the submandibular region with associated benign bone marrow
      elements, with a review of the literature and discussion of the differential
      diagnosis.

PMID- 22623085
TI  - Paranasal sinus mucocele.
AB  - Paranasal sinus mucoceles are epithelium-lined cystic masses usually resulting
      from obstruction of sinus ostia. They most frequently occur in the frontal and
      ethmoid sinuses. While ophthalmologic symptoms are most common, patients also
      report rhinological or neurological complaints. The close proximity of paranasal
      sinus mucoceles to the orbit and skull base predisposes the patient to
      significant morbidity. Computed tomography displays a non-enhancing homogenous
      mass with expansion of bony walls. Magnetic resonance imaging reveals variable
      intensity of T1-weighted images and a hyperintense mass on T2-weighted images.
      Histopathologically mucoceles have features of respiratory mucosa with areas of
      reactive bone formation, hemorrhage, fibrosis, and granulation tissue. Surgical
      excision is the standard treatment with trends towards endoscopic techniques.

PMID- 22623086
TI  - Middle ear adenomas stain for two cell populations and lack myoepithelial cell
      differentiation.
AB  - Middle ear adenomas (MEAs) are benign neoplasms along a spectrum with
      neuroendocrine neoplasms (carcinoid tumors). Immunohistochemical (IHC) staining
      for myoepithelial markers has not been reported in these tumors. The archives of
      the Cleveland Clinic, University of Virginia and Armed Forces Institute of
      Pathology were retrospectively searched for tumors arising within the middle ear
      with material available for IHC staining. Twelve cases of MEAs, four cases of
      jugulotympanic paragangliomas (JPGs), 10 cases of ceruminous adenomas (CAs) and
      four cases of ceruminous adenocarcinomas (CACs) were obtained. IHC staining was
      performed for smooth muscle actin (SMA), p63, S-100 protein, cytokeratin 5/6
      (CK5/6), and cytokeratin 7 (CK7). The MEAs were positive for: CK7 (92 %,
      luminal), CK5/6 (92 %, abluminal), p63 (83 %, abluminal), and negative for SMA
      and S-100 protein. The JPGs were negative for CK7, CK5/6, p63 and SMA; S-100
      protein highlighted sustentacular cells. The CAs were positive for: CK7 (100 %,
      luminal), CK5/6 (100 %, abluminal), S-100 protein (80 %, abluminal), p63 (100 %,
      abluminal), and SMA (90 %, abluminal). CACs demonstrated two patterns, (1)
      adenoid cystic carcinoma-type: positive for CK7 (100 %, luminal), CK5/6, S-100
      protein, p63, and SMA (all 100 %, abluminal); and (2) conventional-type: CK7 (50
      % luminal), and no CK5/6, SMA, S-100 protein, or p63 expression. The IHC profile
      of MEAs suggests that these tumors harbor at least two cell populations,
      including luminal and basal cells. However, unlike ceruminous adenomas, MEAs lack
      true myoepithelial differentiation given the absence of S-100 protein and SMA
      staining in all cases.

PMID- 22623087
TI  - Management of ruptured brain arteriovenous malformations.
AB  - Intracranial arteriovenous malformations (AVMs) are a common cause of stroke in
      younger patients, and often present as intracerebral hemorrhages (ICH),
      associated with 10 % to 30 % mortality. Patients who present with a hemorrhage
      from an AVM should be initially stabilized according to acute management
      guidelines for ICH. The characteristics of a lesion including its size, location
      in eloquent tissue, and high-risk features will influence risk of rupture,
      prognosis, as well as help guide management decisions. Given that rupture is
      associated with an increased risk of 6 % re-rupture in the year following the
      initial hemorrhage, versus 1 % to 3 % predicted annual risk in non-ruptured
      lesions only, definitive treatment is encouraged after ICH stabilization. A rest
      period of 2 to 6 weeks after hemorrhage is recommended before definitive
      treatment to avoid disrupting friable parenchyma and the hematoma. Treatment may
      consist of endovascular embolization, surgical resection, radiosurgery, or a
      combination of these three interventions based on the lesion.

PMID- 22623088
TI  - Exposure to delayed visual feedback of the hand changes motor-sensory synchrony
      perception.
AB  - We examined whether the brain can adapt to temporal delays between a self
      initiated action and the naturalistic visual feedback of that action. During an
      exposure phase, participants tapped with their index finger while seeing their
      own hand in real time (~0 ms delay) or delayed at 40, 80, or 120 ms. Following
      exposure, participants were tested with a simultaneity judgment (SJ) task in
      which they judged whether the video of their hand was synchronous or asynchronous
      with respect to their finger taps. The locations of the seen and the real hand
      were either different (Experiment 1) or aligned (Experiment 2). In both cases,
      the point of subjective simultaneity (PSS) was uniformly shifted in the direction
      of the exposure lags while sensitivity to visual-motor asynchrony decreased with
      longer exposure delays. These findings demonstrate that the brain is quite
      flexible in adjusting the timing relation between a motor action and the
      otherwise naturalistic visual feedback that this action engenders.

PMID- 22623090
TI  - The cost of moving with the left hand.
AB  - Precise left-hand movements take longer than right-hand movements (for right
      handers). To quantify how left-hand movements are affected by task difficulty and
      phase of movement control, we manipulated the difficulty of repetitive speeded
      aiming movements while participants used the left or right hand. We observed left
      hand costs in both initial impulse and current control phases of movement. While
      left-hand cost during the initial impulse phase was small, left-hand cost during
      the current control phase varied from 10 to 60 ms, in direct proportion to the
      movement's difficulty as quantified by Fitts' law (0.77 < R2 < 0.99, across three
      experiments). In particular, in comparison with a difficult task for the right
      hand (Fitts' ID(R) = 6.6), the left hand's task would have to be made easier by
      0.5 bits (ID(L) = 6.1) to be performed as quickly. The left-hand cost may reflect
      the time required for callosal transfer of information between the left and right
      hemispheres during the current control phase of precision left-hand movements or
      reflect movement control differences in the current control phase of movement
      that are inherent to the hemispheres. Overall, the present results support
      multiphase models of movement generation, in which separate specialized processes
      contribute to the launching and completion of precision hand movements.

PMID- 22623089
TI  - How perceived egocentric distance varies with changes in tonic vergence.
AB  - According to the eye muscle potentiation (EMP) hypothesis, sustained vergence
      leads to changes in egocentric perceived distance. This perceptual effect has
      been attributed to a change in the resting or tonic state of vergence. The goal
      of the present study was to test the EMP hypothesis by quantifying the
      relationship between prism-induced changes in tonic vergence and corresponding
      changes in perceived distance and by measuring the dynamics of changes in
      perceived distance. During a 10-min exposure to 5-diopter base-out prisms that
      increased the vergence demand, thirteen right-handed subjects pointed to visual
      targets located within reaching space using their left hand, without visual
      feedback. Pre- and post-exposure tests assessed tonic vergence through phoria
      measurements and egocentric distance estimate through pointing to visual targets
      with each hand successively, without visual feedback. Similar distance
      aftereffects were observed for both hands, although only the left hand was used
      during exposure, indicating that these aftereffects are mediated by visual
      processes rather than by visuomotor interactions. The distance aftereffects were
      significantly correlated with prism-induced changes in phoria, demonstrating a
      relationship between perceived distance and the level of tonic vergence. Changes
      in perceived distance increased monotonically across trials during prism exposure
      and remained stable during the post-test, indicating a long time constant for
      these perceptual effects, consistent with current models of the vergence control
      system. Overall, these results support the hypothesis that vergence plays a role
      in reduced-cue distance perception. They further illustrate that variations in
      tonic vergence influence perceived distance by altering the sensed vergence
      effort.

PMID- 22623091
TI  - Central fixations with rightward deviations: saccadic eye movements on the
      landmark task.
AB  - Neurologically normal individuals show an attentional bias toward the left side,
      which results from right hemisphere activation during visuospatial tasks. The
      strength of this bias is influenced by various factors, such as line length,
      vertical elevation and presentation time. What remains unknown is how
      participants gather information via saccadic eye movements during task
      performance and how this relates to their responses. Eye movements were recorded
      while participants performed the landmark task. Fixations and saccades were both
      analysed to gain a complete understanding of eye movement patterns. Fixations
      tended to focus on the centre of the line, with few left-right differences.
      Saccades were examined by creating histograms illustrating all x-coordinates
      which were examined over the course of each trial. Interestingly, mean eye
      position varied with participant response, with an overall tendency to look to
      the right of centre. Results are consistent with prior research, which has
      primarily looked at fixations and demonstrates the necessity of examining
      saccades as well as fixations in order to see how eye movement patterns relate to
      pseudoneglect.

PMID- 22623092
TI  - See what I hear? Beat perception in auditory and visual rhythms.
AB  - Our perception of time is affected by the modality in which it is conveyed.
      Moreover, certain temporal phenomena appear to exist in only one modality. The
      perception of temporal regularity or structure (e.g., the 'beat') in rhythmic
      patterns is one such phenomenon: visual beat perception is rare. The modality
      specificity for beat perception is puzzling, as the durations that comprise
      rhythmic patterns are much longer than the limits of visual temporal resolution.
      Moreover, the optimization that beat perception provides for memory of auditory
      sequences should be equally relevant to visual sequences. Why does beat
      perception appear to be modality specific? One possibility is that the nature of
      the visual stimulus plays a role. Previous studies have usually used brief
      stimuli (e.g., light flashes) to present visual rhythms. In the current study, a
      rotating line that appeared sequentially in different spatial orientations was
      used to present a visual rhythm. Discrimination accuracy for visual rhythms and
      auditory rhythms was compared for different types of rhythms. The rhythms either
      had a regular temporal structure that previously has been shown to induce beat
      perception in the auditory modality, or they had an irregular temporal structure
      without beat-inducing qualities. Overall, the visual rhythms were discriminated
      more poorly than the auditory rhythms. The beat-based structure, however,
      increased accuracy for visual as well as auditory rhythms. These results indicate
      that beat perception can occur in the visual modality and improve performance on
      a temporal discrimination task, when certain types of stimuli are used.

PMID- 22623093
TI  - Effective connectivity between human supplementary motor area and primary motor
      cortex: a paired-coil TMS study.
AB  - The supplementary motor area (SMA) is important for preparation and execution of
      voluntary movements and densely anatomically connected with the hand area of
      primary motor cortex (M1). However, little is known about the effective
      connectivity between SMA and ipsilateral M1 (SMA -> M1). Here, we used paired
      coil transcranial magnetic stimulation (pcTMS) to study the SMA -> M1 effective
      connectivity in healthy human subjects. In Experiment 1, we tested the effects of
      different induced current directions in the SMA and M1, and different intensities
      of conditioning SMA stimulation. Coil placement over the SMA-proper was verified
      by MRI-navigation. We found a SMA -> M1 facilitatory effect on motor evoked
      potential (MEP) amplitude that occurred very specifically only with an induced
      conditioning current directed from the midline towards the targeted SMA, an
      induced test current in M1 directed antero-medially and sufficient intensity of
      conditioning SMA stimulation. In Experiment 2, we selected these effective
      parameters to explore the effects of SMA -> M1 on the active MEP amplitude,
      cortical silent period (CSP) duration, and using a triple-pulse protocol, on
      short-interval intracortical inhibition (SICI) and intracortical facilitation
      (ICF). None of these measures was affected by conditioning SMA stimulation. Our
      findings demonstrate that pcTMS identifies predominantly facilitatory connections
      from SMA-proper to the hand area of the ipsilateral M1. The successful activation
      of this connection depends on effective SMA-proper stimulation, is state
      dependent and likely mediated via excitatory interneurons in M1.

PMID- 22623094
TI  - Low-frequency physiological activation of the vestibular utricle causes biphasic
      modulation of skin sympathetic nerve activity in humans.
AB  - We have previously shown that sinusoidal galvanic vestibular stimulation, a means
      of selectively modulating vestibular afferent activity, can cause partial
      entrainment of sympathetic outflow to muscle and skin in human subjects. However,
      it influences the firing of afferents from the entire vestibular apparatus,
      including the semicircular canals. Here, we tested the hypothesis that selective
      stimulation of one set of otolithic organs-those located in the utricle, which
      are sensitive to displacement in the horizontal axis-could entrain sympathetic
      nerve activity. Skin sympathetic nerve activity (SSNA) was recorded via tungsten
      microelectrodes inserted into cutaneous fascicles of the common peroneal nerve in
      10 awake subjects, seated (head vertical, eyes closed) on a motorised platform.
      Slow sinusoidal accelerations-decelerations (~4 mG) were applied in the X (antero
      posterior) or Y (medio-lateral) direction at 0.08 Hz; composite movements in both
      directions were also applied. Subjects either reported feeling a vague sense of
      movement (with no sense of direction) or no movement at all. Nevertheless, cross
      correlation analysis revealed a marked entrainment of SSNA for all types of
      movements: vestibular modulation was 97 +/- 3 % for movements in the X axis and
      91 +/- 5 % for displacements in the Y axis. For each sinusoidal cycle, there were
      two major peaks of modulation-one associated with acceleration as the platform
      moved forward or to the side, and one associated with acceleration in the
      opposite direction. We interpret these observations as reflecting inertial
      displacement of the stereocilia within the utricle during acceleration, which
      causes a robust vestibulosympathetic reflex.

PMID- 22623095
TI  - Modeling direction discrimination thresholds for yaw rotations around an earth
      vertical axis for arbitrary motion profiles.
AB  - Understanding the dynamics of vestibular perception is important, for example,
      for improving the realism of motion simulation and virtual reality environments
      or for diagnosing patients suffering from vestibular problems. Previous research
      has found a dependence of direction discrimination thresholds for rotational
      motions on the period length (inverse frequency) of a transient (single cycle)
      sinusoidal acceleration stimulus. However, self-motion is seldom purely
      sinusoidal, and up to now, no models have been proposed that take into account
      non-sinusoidal stimuli for rotational motions. In this work, the influence of
      both the period length and the specific time course of an inertial stimulus is
      investigated. Thresholds for three acceleration profile shapes (triangular,
      sinusoidal, and trapezoidal) were measured for three period lengths (0.3, 1.4,
      and 6.7 s) in ten participants. A two-alternative forced-choice discrimination
      task was used where participants had to judge if a yaw rotation around an earth
      vertical axis was leftward or rightward. The peak velocity of the stimulus was
      varied, and the threshold was defined as the stimulus yielding 75 % correct
      answers. In accordance with previous research, thresholds decreased with
      shortening period length (from ~2 deg/s for 6.7 s to ~0.8 deg/s for 0.3 s). The
      peak velocity was the determining factor for discrimination: Different profiles
      with the same period length have similar velocity thresholds. These measurements
      were used to fit a novel model based on a description of the firing rate of semi
      circular canal neurons. In accordance with previous research, the estimates of
      the model parameters suggest that velocity storage does not influence perceptual
      thresholds.

PMID- 22623096
TI  - Development of postural adjustments during reaching in typically developing
      infants from 4 to 18 months.
AB  - Knowledge on the development of postural adjustments during infancy, in
      particular on the development of postural muscle coordination, is limited. This
      study aimed at the evaluation of the development of postural control during
      reaching in a supported sitting condition. Eleven typically developing infants
      participated in the study and were assessed at the ages of 4, 6, 10 and 18
      months. We elicited reaching movements by presenting small toys at an arm's
      length distance, whilst activity of multiple arm, neck and trunk muscles was
      recorded using surface EMG. A model-based computer algorithm was used to detect
      the onset of phasic muscle activity. The results indicated that postural muscle
      activity during reaching whilst sitting supported is highly variable. Direction
      specific postural activity was inconsistently present from early age onwards and
      increased between 10 and 18 months without reaching a 100 % consistency. The
      dominant pattern of activation at all ages was the 'complete pattern', in which
      all direction-specific muscles were recruited. At 4 months, a slight preference
      for top-down recruitment existed, which was gradually replaced by a preference
      for bottom-up recruitment. We conclude that postural control during the
      ecological task of reaching during supported sitting between 4 and 18 months of
      age is primarily characterized by variation. Already from 4 months onwards,
      infants are-within the variation-sometimes able to select muscle recruitment
      strategies that are optimal to the task at hand.

PMID- 22623097
TI  - Collateralization of projections from the rostral ventrolateral medulla to the
      rostral and caudal thoracic spinal cord in felines.
AB  - Stimulation of vestibular receptors elicits distinct changes in blood flow to the
      forelimb and hindlimb, showing that the nervous system has the capacity to
      produce changes in sympathetic outflow which are specific for a particular region
      of the body. However, it is unclear whether the rostral ventrolateral medulla
      (RVLM), the primary region of the brainstem that regulates sympathetic outflow to
      vascular smooth muscle, has the appropriate connectivity with sympathetic
      preganglionic neurons to generate anatomically patterned responses. To make this
      determination, the retrograde fluorescent tracer Fast Blue was injected into the
      T(4) spinal cord segment of cats, which regulates upper body blood flow, whereas
      Fluoro-Ruby was injected into the T(10) segment to label projections to a region
      of the spinal cord that regulates lower body blood flow. More neurons were single
      labeled by a particular tracer (92 %) than were double labeled by both tracers (8
      %), supporting the notion that the RVLM can regulate sympathetic outflow from a
      limited number of spinal cord segments. Since a large fraction of RVLM neurons
      that control sympathetic outflow in rodents contain epinephrine, we additionally
      determined whether the tracer-labeled cells were immunopositive for the enzyme
      tyrosine hydroxylase (TH), which participates in the synthesis of catecholamines.
      Double labeling by the two tracers injected into the spinal cord was more common
      for TH-immunopositive neurons than for the general population of RVLM neurons: 19
      % of the TH-positive cells contained both Fast Blue and Fluoro-Ruby, 30 %
      contained one of the tracers, and 51 % were not labeled by either tracer.
      Furthermore, many spinally projecting neurons in close proximity to the RVLM
      catecholaminergic neurons (41 % of the population) were not immunopositive for
      TH, suggesting that feline RVLM is neurochemically heterogeneous.

PMID- 22623098
TI  - Properties of spatial channels underlying the detection of orientation
      modulations.
AB  - Orientation-modulated stimuli are thought to be processed via a two-stage
      process, the first stage involving the detection of the carrier by mechanisms in
      striate cortex and the second stage involving the detection of the modulation by
      way of integration of carrier-based information by mechanisms in extra-striate
      cortex. Much is known about the spatial properties of the channels underlying
      carrier detection but less is known about the properties of the channels involved
      in modulation detection. Using a discrimination at detection paradigm, we show
      that the mechanisms underlying modulation detection are tuned for envelope
      spatial frequency and orientation. The tuning of these channels is not
      substantially different from that previously described for carrier mechanisms,
      namely 1-2 octaves for spatial frequency and 30 degrees  for orientation. For
      orientation, these stimuli exhibit an oblique effect that is dependent on
      absolute carrier orientation, suggesting facilitative interactions between first-
      and second-stage processes.

PMID- 22623099
TI  - Spatial biases in number line bisection tasks are due to a cognitive illusion of
      length.
AB  - Placing arrow heads (Judd Illusion) or numbers of different magnitude at the end
      of a line biases perception of the centre of the line. For the Judd Illusion, it
      is known that this bias depends on the method used: a deliberate (more
      perceptually based) marking of the centre with a pen is more subject to the
      illusion than are fast (more action-based) ballistic pointing movements made
      towards the centre. It has been suggested that the number bias also reflects a
      cognitive illusion of length. To test this assumption, we used two different
      response methods in line bisection tasks while lines were flanked by arrow heads
      or numbers of different magnitudes. For both conditions, we found that the more
      action-based response method showed less bias. Since the pattern of biases
      induced by flanking numbers and arrow heads are similar, we confirm that the
      spatial bias produced by numerical magnitude reflects a cognitive illusion of
      length.

PMID- 22623100
TI  - Evaluating the management effectiveness of five protected areas in Taiwan using
      WWF's RAPPAM.
AB  - This study adopts and modifies the WWF Rapid assessment and prioritization of
      protected areas management methodology (RAPPAM) to evaluate the management
      effectiveness of five protected areas in Taiwan. The results indicate that,
      unlike the situation in most developing countries, the threats and pressures
      faced by protected areas in Taiwan come mainly from the outside-with pollution as
      the most common pressure and threat, and difficult for their management
      authorities to deal with effectively. The categories and extent of these
      pressures and threats are related to remoteness and geographic location of the
      protected areas. All five cases under study reveal a similar management approach,
      clear management goals, adequate basic infrastructure and clear management
      decision-making; on the down side, however, all of them suffer from the lack of
      an effective comprehensive management plan, inadequate or poor quality human
      resources and insufficient funding. The present study suggests that first
      priority should be given to strengthening management planning in order to improve
      management effectiveness of protected areas in Taiwan. The adjustment made to
      RAPPAM in this study was to amend and take the format of the management plan as
      the basis for evaluation material preparations and open the discussion to
      encourage stakeholders' participation to open the dialogue among them. The
      results indicate that, although the system evaluation design still has some
      constraints, the quality of information collected is improved and can respond
      more directly to the specific demands of the respective areas.

PMID- 22623101
TI  - A multinational study to develop universal standardization of whole-body bone
      density and composition using GE Healthcare Lunar and Hologic DXA systems.
AB  - Dual-energy x-ray absorptiometry (DXA) is used to assess bone mineral density
      (BMD) and body composition, but measurements vary among instruments from
      different manufacturers. We sought to develop cross-calibration equations for
      whole-body bone density and composition derived using GE Healthcare Lunar and
      Hologic DXA systems. This multinational study recruited 199 adult and pediatric
      participants from a site in the US (n = 40, ages 6 through 16 years) and one in
      China (n = 159, ages 5 through 81 years). The mean age of the participants was
      44.2 years. Each participant was scanned on both GE Healthcare Lunar and Hologic
      Discovery or Delphi DXA systems on the same day (US) or within 1 week (China) and
      all scans were centrally analyzed by a single technologist using GE Healthcare
      Lunar Encore version 14.0 and Hologic Apex version 3.0. Paired t-tests were used
      to test the results differences between the systems. Multiple regression and
      Deming regressions were used to derive the cross-conversion equations between the
      GE Healthcare Lunar and Hologic whole-body scans. Bone and soft tissue measures
      were highly correlated between the GE Healthcare Lunar and Hologic and systems,
      with r ranging from 0.96 percent fat [PFAT] to 0.98 (BMC). Significant
      differences were found between the two systems, with average absolute differences
      for PFAT, BMC, and BMD of 1.4%, 176.8 g and 0.013 g/cm(2) , respectively. After
      cross-calibration, no significant differences remained between GE Healthcare
      Lunar measured results and the results converted from Hologic. The equations we
      derived reduce differences between BMD and body composition as determined by GE
      Healthcare Lunar and Hologic systems and will facilitate combining study results
      in clinical or epidemiological studies.

PMID- 22623102
TI  - [Isolated fracture of the trapezium, a rare wrist fracture after a fall on the
      hand].

PMID- 22623103
TI  - [Variation of the anterior cruciate ligament (a separate anteromedial bundle)].

PMID- 22623104
TI  - Parental smoking may confer negligible environmental, but significant lifestyle
      costs to childhood cancer survivors.

PMID- 22623105
TI  - Evaluation of SCO1 deletion on Saccharomyces cerevisiae metabolism through a
      proteomic approach.
AB  - The Saccharomyces cerevisiae gene SCO1 has been shown to play an essential role
      in copper delivery to cytochrome c oxidase. Biochemical studies demonstrated
      specific transfer of copper from Cox17p to Sco1p, and physical interactions
      between the Sco1p and Cox2p. Deletion of SCO1 yeast gene results in a respiratory
      deficient phenotype. This study aims to gain a more detailed insight on the
      effects of SCO1 deletion on S. cerevisiae metabolism. We compared, using a
      proteomic approach, the protein pattern of SCO1 null mutant strain and wild-type
      BY4741 strain grown on fermentable and on nonfermentable carbon sources. The
      analysis showed that on nonfermentable medium, the SCO1 mutant displayed a
      protein profile similar to that of actively fermenting yeast cells. Indeed, on 3%
      glycerol, this mutant displayed an increase of some glycolytic and fermentative
      enzymes such as glyceraldehyde-3-phosphate dehydrogenase 1, enolase 2, pyruvate
      decarboxylase 1, and alcohol dehydrogenase 1. These data were supported by
      immunoblotting and enzyme activity assay. Moreover, the ethanol assay and the
      oxygen consumption measurement demonstrated a fermentative activity in SCO1
      mutant on respiratory medium. Our results suggest that on nonfermentable carbon
      source, the lack of Sco1p causes a metabolic shift from respiration to
      fermentation.

PMID- 22623107
TI  - Mass spectrometric identification of novel posttranslational modification sites
      in Huntingtin.
AB  - Huntington's disease (HD) is caused by a CAG triplet repeat expansion in exon 1
      of the Huntingtin (Htt) gene, encoding an abnormal expanded polyglutamine (polyQ)
      tract that confers toxicity to the mutant Htt (mHtt) protein. Recent data suggest
      that posttranslational modifications of mHtt modulate its cytotoxicity. To
      further understand the cytotoxic mechanisms of mHtt, we have generated HEK293
      cell models stably expressing Strep- and FLAG-tagged Htt containing either 19Q
      (wild-type Htt), 55Q (mHtt), or 94Q (mHtt) repeats. Following tandem affinity
      purification, the tagged Htt and associated proteins were subjected to tandem
      mass spectrometry or 2D nano-LC tandem mass spectrometry and several novel
      modification sites of mHtt containing 55Q or 94Q were identified. These were
      phosphorylation sites located at Ser431 and Ser432, and ubiquitination site
      located at Lys444. The two phosphorylation sites were confirmed by Western blot
      analysis using phosphorylation site-specific antibodies. In addition, prevention
      of phosphorylation at the two serine sites altered mHtt toxicity and
      accumulation. These modifications of mHtt may provide novel therapeutic targets
      for effective treatment of the disorder.

PMID- 22623106
TI  - Saracatinib (AZD0530) is a potent modulator of ABCB1-mediated multidrug
      resistance in vitro and in vivo.
AB  - Saracatinib, a highly selective, dual Src/Abl kinase inhibitor, is currently in a
      Phase II clinical trial for the treatment of ovarian cancer. In our study, we
      investigated the effect of saracatinib on the reversal of multidrug resistance
      (MDR) induced by ATP-binding cassette (ABC) transporters in vitro and in vivo.
      Our results showed that saracatinib significantly enhanced the cytotoxicity of
      ABCB1 substrate drugs in ABCB1 overexpressing HeLa/v200, MCF-7/adr and
      HEK293/ABCB1 cells, an effect that was stronger than that of gefitinib, whereas
      it had no effect on the cytotoxicity of the substrates in ABCC1 overexpressing HL
      60/adr cells and its parental sensitive cells. Additionally, saracatinib
      significantly increased the doxorubicin (Dox) and Rho 123 accumulation in
      HeLa/v200 and MCF-7/adr cells, whereas it had no effect on HeLa and MCF-7 cells.
      Furthermore, saracatinib stimulated the ATPase activity and inhibited
      photolabeling of ABCB1 with [(125)I]-iodoarylazidoprazosin in a concentration
      dependent manner. In addition, the homology modeling predicted the binding
      conformation of saracatinib within the large hydrophobic drug-binding cavity of
      human ABCB1. However, neither the expression level of ABCB1 nor the
      phosphorylation level of Akt was altered at the reversal concentrations of
      saracatinib. Importantly, saracatinib significantly enhanced the effect of
      paclitaxel against ABCB1-overexpressing HeLa/v200 cancer cell xenografts in nude
      mice. In conclusion, saracatinib reverses ABCB1-mediated MDR in vitro and in vivo
      by directly inhibiting ABCB1 transport function, without altering ABCB1
      expression or AKT phosphorylation. These findings may be helpful to attenuate the
      effect of MDR by combining saracatinib with other chemotherapeutic drugs in the
      clinic.

PMID- 22623108
TI  - A phenomenological model for chemico-mechanically induced cell shape changes
      during migration and cell-cell contacts.
AB  - A phenomenological model for the evolution of shape transition of cells is
      considered. These transitions are determined by the emission of growth-factors,
      as well as mechanical interaction if cells are subjected to hard impingement. The
      originality of this model necessitates a formal treatment of the mathematical
      model, as well as the presentation of elementary cases in order to illustrate the
      consistence of the model. We will also show some small-scale relevant
      applications.

PMID- 22623110
TI  - A chemo-mechanical constitutive model for transiently cross-linked actin networks
      and a theoretical assessment of their viscoelastic behaviour.
AB  - Biological materials can undergo large deformations and also show viscoelastic
      behaviour. One such material is the network of actin filaments found in
      biological cells, giving the cell much of its mechanical stiffness. A theory for
      predicting the relaxation behaviour of actin networks cross-linked with the cross
      linker alpha-actinin is proposed. The constitutive model is based on a continuum
      approach involving a neo-Hookean material model, modified in terms of
      concentration of chemically activated cross-links. The chemical model builds on
      work done by Spiros (Doctoral thesis, University of British Columbia, Vancouver,
      Canada, 1998) and has been modified to respond to mechanical stress experienced
      by the network. The deformation is split into a viscous and elastic part, and a
      thermodynamically motivated rate equation is assigned for the evolution of
      viscous deformation. The model predictions were evaluated for stress relaxation
      tests at different levels of strain and found to be in good agreement with
      experimental results for actin networks cross-linked with alpha-actinin.

PMID- 22623109
TI  - Progressive structural and biomechanical changes in elastin degraded aorta.
AB  - Aortic aneurysm is an important clinical condition characterized by common
      structural changes such as the degradation of elastin, loss of smooth muscle
      cells, and increased deposition of fibrillary collagen. With the goal of
      investigating the relationship between the mechanical behavior and the
      structural/biochemical composition of an artery, this study used a simple
      chemical degradation model of aneurysm and investigated the progressive changes
      in mechanical properties. Porcine thoracic aortas were digested in a mild
      solution of purified elastase (5 U/mL) for 6, 12, 24, 48, and 96 h. Initial size
      measurements show that disruption of the elastin structure leads to increased
      artery dilation in the absence of periodic loading. The mechanical properties of
      the digested arteries, measured with a biaxial tensile testing device, progress
      through four distinct stages termed (1) initial-softening, (2) elastomer-like,
      (3) extensible-but-stiff, and (4) collagen-scaffold-like. While stages 1, 3, and
      4 are expected as a result of elastin degradation, the S-shaped stress versus
      strain behavior of the aorta resulting from enzyme digestion has not been
      reported previously. Our results suggest that gradual changes in the structure of
      elastin in the artery can lead to a progression through different mechanical
      properties and thus reveal the potential existence of an important transition
      stage that could contribute to artery dilation during aneurysm formation.

PMID- 22623111
TI  - Earthworm metabolomic responses after exposure to aged PCB contaminated soils.
AB  - (1)H NMR metabolomics was used to measure earthworm sub-lethal responses to
      polychlorinated biphenyls (PCBs) in historically contaminated (>30 years) soils
      (91-280 mg/kg Aroclor 1254/1260) after two and 14 days of exposure. Although our
      previous research detected a distinct earthworm metabolic response to PCBs in
      freshly spiked soil at lower concentrations (0.5-25 mg/kg Aroclor 1254), the
      results of this study suggest only weak or non-significant relationships between
      earthworm metabolic profiles and soil PCB concentrations. This concurs with the
      expectation that decades of contaminant aging have likely decreased PCB
      bioavailability and toxicity in the field. Instead of being influenced by soil
      contaminant concentration, earthworm metabolic profiles were more closely
      correlated to soil properties such as total soil carbon and soil inorganic
      carbon. Overall, these results suggested that (1)H NMR metabolomics may be
      capable of detecting both site specific responses and decreased contaminant
      bioavailability to earthworms after only two days of exposure, whereas
      traditional toxicity tests require much more time (e.g. 14 days for acute
      toxicity and >50 days for reproduction tests). Therefore, there is significant
      opportunity to develop earthworm metabolomics as a sensitive tool for rapid
      assessment of the toxicity associated with contaminated field soils.

PMID- 22623112
TI  - Integrated approach to assessing the effects of soils polluted with heavy metals
      on a plant population.
AB  - This study addresses the effects of soil polluted with more than one heavy metal
      in a grass species. A 16-week bioassay with Avena sativa L. was conducted in
      microcosms using soils from two abandoned mines in central Spain that contained
      levels above World Health Organization (WHO) reference limits for soils of more
      than three heavy metals. Pollution effects were examined at cell, tissue, organ,
      plant and population levels. For this purpose, dry weight, maximum height and
      number of leaves were determined; leaf tissues were observed by low temperature
      scanning electron microscopy; the metal contents of roots and shoots were
      determined by plasma emission spectroscopy and their distribution in different
      tissues was analyzed by X-ray microanalysis using an environmental scanning
      electron microscope. The results explain the accumulation and translocation of
      soil metals by this plant species; their effects in cells, tissues and growth of
      plants; and allow inference on population effects. The discussion of the
      methodological approach leads us to propose a valid protocol to assess the
      effects of a set of heavy metals present in the topsoil of polluted sites on a
      plant population. We recommend its use for an ecotoxicological diagnosis and risk
      analysis of similarly polluted sites.

PMID- 22623113
TI  - Dissolution of weak acids under laminar flow and rotating disk hydrodynamic
      conditions: application of a comprehensive convection-diffusion-migration
      reaction transport model.
AB  - A steady-state mass transfer model that incorporates convection, diffusion, ionic
      migration, and ionization reaction processes was extended to describe the
      dissolution of weak acids under laminar flow and a rotating disk hydrodynamics.
      The model accurately predicted the experimental dissolution rates of benzoic
      acid, 2-naphthoic acid, and naproxen in unbuffered and monoprotic buffers within
      the physiological pH range for both hydrodynamic systems. Simulations at various
      flow rates indicated a cube root dependency of dissolution rate on the flow rate
      for a given bulk pH value for the laminar hydrodynamic system, as proposed
      earlier by Shah and Nelson (1975. J Pharm Sci 64(9):1518-1520) for neutral
      compounds. The model has limitations in its ability to accurately predict the
      dissolution of weak acids under certain conditions that imposed steep
      concentration gradients, such as high pH values, and for polyprotic buffer
      systems that caused the numerical solution to be unstable, suggesting that
      alternative numerical techniques may be required to obtain a stable numerical
      solution at all conditions. The model presents many advantages, most notably the
      ability to successfully predict the complex process under physiological
      conditions without simplifying assumptions, and therefore accurately representing
      the system in a comprehensive manner.

PMID- 22623114
TI  - Success rate and complications of endonasal dacryocystorhinostomy with
      unciformectomy.
AB  - BACKGROUND: Endonasal dacryocystorhinostomy (DCR) has been widely used to treat
      nasolacrimal duct obstruction. Here, we evaluated the anatomical advantages of
      the uncinate process as a landmark and to study the effect of unciformectomy on
      success rate and complications of endonasal DCR . METHODS: In total, 288 eyes of
      265 adult patients who underwent endonasal DCR between January 2003 and February
      2010 were reviewed retrospectively. The eyes were classified into two groups,
      according to whether unciformectomy was performed or not. All surgical procedures
      and surgical indications were the same except unciformectomy and endonasal DCR
      was performed by one surgeon. Unciformectomy was performed by resecting the
      anterior part of uncinate process. RESULTS: One hundred and eighty-six eyes of
      168 patients received endonasal DCR with unciformectomy, and 102 eyes of 97
      patients received endonasal DCR alone. The average success rate of endonasal DCR
      with unciformectomy was 97.8 % and that of endonasal DCR alone was 90.2 %, with
      statistically significant difference (Student's t-test, p-value < 0.05). There
      were 14 eyes with post-operative nasolacrimal obstruction, caused by granuloma in
      five eyes, intranasal synechia in two eyes, membranous obstruction in six eyes,
      and canalicular stenosis in one eye. There were no serious complications such as
      orbital fat prolapse, cerebrospinal fluid leak, or delayed hemorrhage.
      CONCLUSIONS: Anterior resection of the uncinate process gives improved access to
      the lacrimal bone by exposing the medial aspect of the lacrimal fossa and forming
      the precise location of the osteotomy on the lacrimal bone during endonasal DCR.
      Thus, the uncinate process can be used as an anatomical landmark for endonasal
      DCR. The unciformian endonasal DCR improves operation success rate by allowing
      access to the large space of the nasal cavity and reducing the synechiae of the
      nasal cavity.

PMID- 22623116
TI  - Treatment of non-arteritic anterior ischemic optic neuropathy with high-dose
      systemic corticosteroid therapy.

PMID- 22623115
TI  - Glial proliferation after vitrectomy for a macular hole: a spectral domain
      optical coherence tomography study.
AB  - PURPOSE: To characterize eyes with glial proliferation after macular hole (MH)
      surgery. METHODS: We retrospectively reviewed patients who underwent vitrectomy
      for an idiopathic MH using spectral domain optical coherence tomography (SD-OCT).
      The pattern of the closed MH after surgery was categorized according to the
      presence (group 1) or absence (group 2) of apparent glial proliferation, which
      was determined by glial tissue reflectivity involving the external limiting
      membrane (ELM) and photoreceptor layers. Photoreceptor layer defect areas were
      categorized as mild or severe. Best-corrected visual acuity (BCVA) and pre- and
      postoperative OCT parameters were compared between the two groups. RESULTS: Among
      30 eyes followed-up for a median of 11 months, seven (23 %) were assigned to
      group 1 and 23 (77 %) to group 2. The median age was higher in group 1 (70 years)
      than in group 2 (63 years). The postoperative BCVA was poorer in group 1 than in
      group 2 at 3 months and at the final examination (P = 0.022 and P < 0.001
      respectively). The median preoperative basal hole diameter in group 1 (1,219 MUm)
      was larger than that of group 2 (590 MUm) (P = 0.002). The MH index (hole
      height/basal hole diameter) was smaller in group 1 than in group 2 (P = 0.012).
      At the final examination, group 1 had larger mild and severe photoreceptor layer
      defect areas (medians 1,300 MUm and 207 MUm respectively) than group 2 (medians
      110 MUm and 70 MUm respectively) (P < 0.001 and P < 0.001 respectively).
      CONCLUSIONS: Eyes with glial proliferation after surgery for MH had different
      preoperative characteristics than eyes with no evidence of glial proliferation.
      In addition to a large hole diameter, other factors such as a small MH index and
      advanced age could be involved in the development of glial proliferation.

PMID- 22623117
TI  - Mesenchymal stem cells associated with porous chitosan-gelatin scaffold: a
      potential strategy for alveolar bone regeneration.
AB  - Tissue engineering has emerged as a novel treatment for replacement of lost bone
      tissue. This study evaluated the effects of a chitosan-gelatin scaffold seeded
      with bone marrow mesenchymal stem cells (BMMSCs) in the healing process of tooth
      sockets in rats. BMMSCs isolated from transgenic rats expressing enhanced green
      fluorescent protein (eGFP) were expanded and seeded on a chitosan-gelatin
      scaffold. These constructs were cultured for three days and characterized by
      scanning electronic microscopy (SEM) and energy dispersion spectroscopy (EDS).
      Receptor rats received the implant in the left sockets, after upper first-molar
      extraction. Right alveoli served as control. Animals were sacrificed at days 5,
      21, and 35 post-graft for examination. Morphometry demonstrated increased bone
      mineralization after 21 and 35 days in transplanted sockets. Migration,
      differentiation, and fate of eGFP-labeled BMMSCs were monitored by
      immunohistochemistry. Tartrate-resistant acid phosphatase staining (TRAP) was
      carried out at 21 days, to identify the involvement of osteoclastic cells in the
      scaffold resorption. The biomaterial was resorbed by TRAP-negative giant cells in
      a typical foreign body reaction. Immunohistochemical findings showed that BMMSCs
      contributed to bone, epithelial, and vascular repair. Together, results indicate
      that BMMSCs loaded in the chitosan-gelatin scaffold is a strategy for tissue
      development in bone engineering.

PMID- 22623118
TI  - Pancreas-sparing duodenectomy in a patient with acute corrosive injury.

PMID- 22623119
TI  - Clinical manifestations of dermatomyositis and clinically amyopathic
      dermatomyositis patients with positive expression of anti-melanoma
      differentiation-associated gene 5 antibody.
AB  - OBJECTIVE: To investigate the clinical features of dermatomyositis (DM) and
      clinically amyopathic DM (CADM) patients with the presence of anti-melanoma
      differentiation-associated gene 5 (anti-MDA-5) antibodies. METHODS: We screened
      the serum anti-MDA-5 antibody levels of 140 patients with various connective
      tissue diseases (CTDs), including 32 with DM and 32 with CADM, or idiopathic
      pulmonary fibrosis (IPF). The clinical courses of DM/CADM patients with a
      positive expression of anti-MDA-5 antibodies were delineated. RESULTS: Anti-MDA-5
      antibodies were detected at a significantly higher frequency in CADM patients
      than in DM patients (12 of 32 versus 3 of 32; P = 0.016), but were not detected
      in patients with other CTDs or IPF and healthy controls. Patients with a positive
      expression of anti-MDA-5 antibodies developed significantly more skin ulcerations
      (12 of 15 versus 4 of 49; P < 0.001) and interstitial lung disease (ILD; 15 of 15
      versus 31 of 49 [P = 0.003]) than those without anti-MDA-5 antibodies. High
      resolution computed tomography scores of the MDA-5-positive subset were increased
      compared with the MDA-5-negative group (mean +/- SD 117.7 +/- 76.3 versus 54.4 +/
      50.7; P = 0.004), and the scores correlated well with anti-MDA-5 antibody levels
      (r(2)  = 0.582, P = 0.029). The respiratory symptoms as well as skin ulcerations
      were dramatically improved in patients with anti-MDA-5 antibody levels <500
      units/ml after treatment, whereas patients with anti-MDA-5 antibody levels >500
      units/ml were resistant to the treatment and died of respiratory failure in a
      short period of time. CONCLUSION: Anti-MDA-5 antibody levels closely correlate
      with the severity of skin ulcerations, ILD, and the prognosis of the disease.
      Dynamic observation of serum anti-MDA-5 antibody levels would be helpful in
      predicting the course of ILD and facilitating better therapeutic targeting.

PMID- 22623121
TI  - The Treatment experience, burden, and unmet needs (TRIBUNE) study - measuring the
      socioeconomic consequences of Multiple Sclerosis.

PMID- 22623120
TI  - Vertebral fragility and structural redundancy.
AB  - The mechanisms of age-related vertebral fragility remain unclear, but may be
      related to the degree of "structural redundancy" of the vertebra; ie, its ability
      to safely redistribute stress internally after local trabecular failure from an
      isolated mechanical overload. To better understand this issue, we performed
      biomechanical testing and nonlinear micro-CT-based finite element analysis on 12
      elderly human thoracic ninth vertebral bodies (age 76.9 +/- 10.8 years). After
      experimentally overloading the vertebrae to measure strength, we used nonlinear
      finite element analysis to estimate the amount of failed tissue and understand
      the failure mechanisms. We found that the amount of failed tissue per unit bone
      mass decreased with decreasing bone volume fraction (r(2)  = 0.66, p < 0.01).
      Thus, for the weak vertebrae with low bone volume fraction, overall failure of
      the vertebra occurred after failure of just a tiny proportion of the bone tissue
      (<5%). This small proportion of failed tissue had two sources: the existence of
      fewer vertically oriented load paths to which load could be redistributed from
      failed trabeculae; and the vulnerability of the trabeculae in these few load
      paths to undergo bending-type failure mechanisms, which further weaken the bone.
      Taken together, these characteristics suggest that diminished structural
      redundancy may be an important aspect of age-related vertebral fragility:
      vertebrae with low bone volume fraction are highly susceptible to collapse
      because so few trabeculae are available for load redistribution if the external
      loads cause any trabeculae to fail.

PMID- 22623123
TI  - Treatment experience, burden and unmet needs (TRIBUNE) in MS study: results from
      France.

PMID- 22623122
TI  - Treatment experience, burden and unmet needs (TRIBUNE) in MS study: results from
      five European countries.
AB  - BACKGROUND: Multiple sclerosis (MS) is a common cause of neurological disability
      in young adults. The TRIBUNE study provides a detailed exploration of costs in
      relation to relapses and disease severity, and assesses the quality of life
      impact on MS patients in terms of utilities, fatigue and activities of daily
      living (ADL). METHODS: Patients in five European countries (France, Germany,
      Italy, Spain and the United Kingdom) completed a self-administered web-based
      questionnaire capturing information on demographics, disease characteristics and
      severity (EDSS), co-morbidities, relapses, resource consumption, utilities,
      fatigue, and activities of daily living. RESULTS: In total, 1261 MS patients
      completed the questionnaire. More than half of the patients (68%) had the
      relapsing-remitting form of the disease; 87% of the sample reported receiving MS
      treatments. Costs were higher with advancing disease severity; for mild patients
      (EDSS score <= 3) the costs ranged between ?13,534 and ?22,461 across countries;
      for moderate (EDSS score 4 - 6.5) between ?28,524 and ?43,948; for severe (EDSS
      >= 7) between ?39,592 and ?65,395. Relapses were also associated with increasing
      costs; the difference in the cost per patient per year for relapsing-remitting
      patients with EDSS score <= 5 that did experience at least one relapse during the
      past 12 months and those who did not ranged between ?3321 and ?9430. The quality
      of life of patients decreased with disease progression and existence of relapses.
      CONCLUSION: The TRIBUNE study provides an important update on the economic burden
      of MS in an era of more widespread use of disease-modifying therapies. It
      explores the cost of MS linked to relapses and disease severity, and examines the
      impact of MS on additional health outcomes beyond utilities such as ADL and
      fatigue.

PMID- 22623124
TI  - Treatment experience, burden and unmet needs (TRIBUNE) in MS study: results from
      Germany.

PMID- 22623125
TI  - Treatment experience, burden and unmet needs (TRIBUNE) in MS study: results from
      Italy.

PMID- 22623126
TI  - Treatment experience, burden and unmet needs (TRIBUNE) in MS study: results from
      Spain.

PMID- 22623127
TI  - Treatment experience, burden and unmet needs (TRIBUNE) in MS study: results from
      the United Kingdom.

PMID- 22623128
TI  - C3-symmetric trisimidazoline-catalyzed enantioselective bromolactonization of
      internal alkenoic acids.
AB  - A method for conducting enantioselective bromolactonization reactions of
      trisubstituted alkenoic acids, using the C(3)-symmetric trisimidazoline 1 and 1,3
      dibromo-5,5-dimethyl hydantoin as a bromine source, has been developed. The
      process generates chiral delta-lactones that contain a quaternary carbon. The
      results of studies probing geometrically different olefins show that (Z)-olefins
      rather than (E)-olefins are favorable substrates for the process. The method is
      not only applicable to acyclic olefin reactants but can also be employed to
      transform cyclic trisubstituted olefins into chiral spirocyclic lactones.
      Finally, the synthetic utility of the newly developed process is demonstrated by
      its application to a concise synthesis of tanikolide, an antifungal marine
      natural product.

PMID- 22623129
TI  - Contrast-enhanced ultrasound examination of the breast: a literature review.
AB  - Angiogenesis is the basis for neoplastic growth in human tissues. Nevertheless,
      neovascularization may be present both in benign and malignant lesions. Although
      microvascular density assessment is a useful tool for the study of neoplastic
      vascularization, it cannot be used on a large scale because of the invasiveness
      of the method. When contrast-enhanced ultrasonography (CEUS) was introduced in
      clinical practice, the initial results in the field of breast lesions were
      disappointing because differentiation between benign and malignant masses was not
      possible. Magnetic resonance imaging (MRI) assessment of the microvascular
      features was therefore immediately accepted because of the higher diagnostic
      accuracy. However, in the last decade the sensitivity and specificity of CEUS
      have greatly improved due to the development of more sophisticated ultrasound
      (US) equipment, the introduction of second-generation contrast agents and the
      development of dedicated software able to perform quantitative analysis. This
      literature review compares the main results reported in the literature regarding
      the use of CEUS for the characterization of neoplastic lesions of the breast. All
      the authors agreed that malignant lesions show early wash-in with more intense
      enhancement and fast wash-out in comparison with benign masses. However, there is
      still no observer agreement regarding vascularization patterns, and different
      classifications are proposed. The conclusion of this literature review is
      therefore that the clinical role of CEUS in the diagnostic process and in follow
      up is still to be clearly defined.

PMID- 22623130
TI  - Fetal loss rate and associated risk factors after amniocentesis, chorionic villus
      sampling and fetal blood sampling.
AB  - PURPOSE: To assess the total and procedure-related fetal loss rate and associated
      risk factors following amniocentesis (AC), chorionic villus sampling (CVS) and
      fetal blood sampling (FBS). MATERIALS AND METHODS: We performed a retrospective
      analysis of patients with invasive diagnostics from 1993 to 2011 in two tertiary
      referral centers. We aimed to classify pregnancy loss after an invasive procedure
      and included the time after the invasive procedure and the result of targeted
      ultrasound/karyotype analysis in the analysis. Fetal losses occurring within two
      weeks after an invasive procedure were classified as procedure-related. RESULTS:
      After excluding 1553 pregnancies with abnormal karyotype, fetal malformations and
      multiple insertions, 6256 cases were retrieved for final analysis. The total
      fetal loss rate was 1.5 %. The procedure-related fetal loss rate was 0.4 % for
      AC, 1.1 % for CVS and 0.4 % for FBS. Maternal vaginal bleeding in the first
      trimester was significantly associated with an increased procedure-related fetal
      loss rate (p= 0.008). The number of invasive procedures declined during the study
      period with increasing numbers of CVS in the first trimester. CONCLUSION: In our
      population the procedure-related fetal loss rate was 0.4 % after AC and 1.1 % and
      0.4 % after CVS and FBS, respectively. Different gestational ages at the time of
      invasive procedures might account in part for those differences. Vaginal bleeding
      during the first trimester is associated with increased procedure-related fetal
      loss. Overall, declining numbers of invasive procedures are the result of
      changing attitudes toward invasive procedures and more sophisticated noninvasive
      prenatal screening programs over the last 20 years.

PMID- 22623131
TI  - Assessment of cardiac function in monochorionic diamniotic twin pregnancies with
      twin-to-twin transfusion syndrome before and after fetoscopic laser
      photocoagulation using Speckle tracking.
AB  - PURPOSE: To assess cardiac function with Speckle tracking in fetuses with twin-to
      twin transfusion syndrome (TTTS) before and after laser therapy. MATERIALS AND
      METHODS: A prospective case control study was conducted on 11 monochorionic
      diamniotic twin pairs with TTTS. Based on normal curves derived from healthy
      controls, global systolic longitudinal myocardial velocity, strain and strain
      rate values were transformed to z-scores. RESULTS: Right and left ventricular
      systolic global strain (-27.45 % and -22.41 %) and strain rate (-4.13/sec and 
      3.27/sec) were reduced in recipients compared with normal values and all
      parameters tended to decrease even more after treatment (RV and LV: strain -23.79
      % and -20.21 %; strain rate: -3.67/sec and -2.87/sec). The corresponding
      measurements in donor fetuses revealed no statistical difference compared to
      reference values. CONCLUSION: The global systolic myocardial function of donor
      twins before and after laser therapy was in the normal ranges. In contrast,
      recipient twins exhibited global cardiac dysfunction with decreased pre- and
      postoperative strain and strain rate. Speckle tracking can identify compromised
      ventricular myocardial function in fetuses with TTTS.

PMID- 22623132
TI  - Automatic texture-based analysis in ultrasound imaging of ovarian masses.
AB  - PURPOSE: To assess the diagnostic accuracy of a new automatic texture-based
      algorithm (ATBA) in ultrasound imaging of ovarian masses and to compare its
      performance to subjective assessment by examiners with different levels of
      ultrasound experience. MATERIALS AND METHODS: A total of 105 ultrasound images
      from three different groups of ovarian lesions (malignancies, functional cysts,
      and dermoid cysts) were evaluated using ATBA and by a total of 36 examiners with
      four different levels of experience (9 junior trainees, 8 senior trainees, 11
      senior gynecologists, and 8 experts). Cohen's kappa, Youden's indices, and the
      sensitivity and specificity of ATBA and of each observer were calculated for
      every subgroup of ovarian lesions. RESULTS: ATBA classified 78 of the 105 masses
      correctly (kappa = 0.62) - results that were significantly better than those of
      the junior and senior trainees (p = 0.02 and p < 0.01), while differences from
      the group of level II examiners did not reach statistical significance (p =
      0.27). The best diagnostic performance (kappa = 0.70) was obtained by the group
      of expert level III ultrasonographers. The best classification rates overall,
      including both ATBA and subjective assessments, were achieved in the detection of
      functional cysts (Youden's indices from 0.73 to 0.85), while the poorest
      diagnostic performance was obtained for the classification of dermoid cysts
      (Youden's indices from 0.28 to 0.55). CONCLUSION: ATBA showed a significantly
      better diagnostic performance than observers with low or medium levels of
      experience, emphasizing its potential value for training purposes and in
      providing additional diagnostic assistance for inexperienced observers.

PMID- 22623133
TI  - Reliability of cervix elastography in the late first and second trimester of
      pregnancy.
AB  - PURPOSE: To evaluate the reliability of cervical elastography as a new ultrasound
      tool for cervical stiffness assessment in pregnancy. MATERIALS AND METHODS: Pilot
      prospective cohort study including 10 consecutive unselected pregnancies in the
      late first and second trimester. Ultrasound was performed by two blinded
      experienced operators using a 9-MHz vaginal probe. One raw dataset per patient
      was acquired by each operator after two cycles of gentle compression and
      relaxation of the cervix. Strain values were independently assessed by each
      operator using commercial offline analysis software (TDI-Q: Tissue Doppler
      Imaging - Quantification, Toshiba Medical Systems). The interobserver reliability
      of strain measurements was evaluated using the intraclass correlation coefficient
      (ICC). RESULTS: The mean +/- SD gestational week of the study population was 19
      +/- 4.1.  Raw data acquirement and strain evaluation were feasible in all ten
      patients. In total, 40 strain measurements were performed: 20 for each operator
      (10 for self-acquired raw data and 10 for raw data acquired by the other
      operator). The mean strain value was 0.33 +/- 0.05, the mean of the differences
      among the measurements was 10.77 % +/- 4.41 %. The obtained interobserver ICC
      agreement values comparing the different subsets of strain measurement ranged
      between 0.91 and 0.96. CONCLUSION: Late first and second trimester cervical
      elastography was shown to be feasible and to have a high interobserver
      reliability. Its clinical value needs to be assessed in further studies on
      selected obstetric populations.

PMID- 22623134
TI  - Contrast-enhanced ultrasonographic (CEUS) and elastosonographic features of a
      case of testicular Leydig tumor.

PMID- 22623135
TI  - Paclitaxel-induced neuropathic pain is age dependent and devolves on glial
      response.
AB  - BACKGROUND: Paclitaxel is an antimitotic antitumour drug highly effective against
      a broad range of cancers considered refractory to conventional chemotherapy. One
      of the main serious side effects of paclitaxel treatment is the induction of
      peripheral neuropathic pain that often diminishes the patient's quality of life.
      In this study, we evaluated the severity of the neuropathy induced by paclitaxel
      and the inflammatory reaction in the dorsal horn of the spinal cord in young,
      adult and aged male CD1 mice. METHOD: Hyperalgesia to noxious thermal stimulus
      and allodynia to non-noxious mechanical stimulus were evaluated using the plantar
      test and the von Frey filament model, respectively. Spinal cord microglia and
      astrocytes expression was assessed using Iba1 and glial fibrillary acidic protein
      immunofluorescence staining, respectively. RESULTS: All groups of mice showed a
      higher nociceptive reaction to thermal noxious (hyperalgesia) and mechanical non
      noxious (allodynia) stimuli after paclitaxel treatment. However, these signs of
      neuropathy were enhanced in young mice followed by aged animals. Additionally,
      paclitaxel evoked a marked microglial and astrocytic response in the spinal cord
      of young and aged mice, whereas this enhanced reactivity was less important in
      adult mice. Indeed, the most severe glial activation observed in juvenile animals
      correlated well with major signs of neuropathy in this group of age. CONCLUSION:
      Our results demonstrate that paclitaxel-induced neuropathy in mice is an age
      dependent phenomenon whose severity devolves on glial response.

PMID- 22623136
TI  - A universal surrogate peptide to enable LC-MS/MS bioanalysis of a diversity of
      human monoclonal antibody and human Fc-fusion protein drug candidates in pre
      clinical animal studies.
AB  - For the development of human antibody Fc (fraction crystallizable) region
      containing therapeutic protein candidates, which can be either monoclonal
      antibodies (mAbs) or pharmacologically active proteins/peptides fused to the Fc
      region of human Immunoglobulin G (IgG), reliable quantification of these proteins
      in animal pharmacokinetic study plasma samples is critical. LC-MS/MS has emerged
      as a promising assay platform for this purpose. LC-MS/MS assays used for
      bioanalysis of human antibody Fc region-containing therapeutic protein candidates
      frequently rely upon quantification of a 'signature' surrogate peptide whose
      sequence is unique to the protein analyte of interest. One drawback of the
      signature peptide approach is that a new LC-MS/MS assay must be developed for
      each new human Fc region-containing therapeutic protein. To address this issue,
      we propose an alternative 'universal surrogate peptide' approach for the
      quantification of human antibody Fc region-containing therapeutic protein
      candidates in plasma samples from all nonclinical species. A single surrogate
      tryptic peptide was identified in the Fc region of most human antibody Fc
      containing therapeutic protein candidates. An LC-MS-MS method based upon this
      peptide was shown to be capable of supporting bioanalysis of a diversity of human
      Fc region-containing therapeutic protein candidates in plasma samples of all
      commonly used animal species.

PMID- 22623138
TI  - Altruistic punishment and between-group competition : evidence from n-person
      prisoner's dilemmas.
AB  - Collective action, or the large-scale cooperation in the pursuit of public goods,
      has been suggested to have evolved through cultural group selection. Previous
      research suggests that the costly punishment of group members who do not
      contribute to public goods plays an important role in the resolution of
      collective action dilemmas. If large-scale cooperation sustained by the
      punishment of defectors has evolved through the mechanism of cultural group
      selection, two implications regarding costly punishment follow: (1) that people
      are more willing to punish defecting group members in a situation of intergroup
      competition than in a single-group social dilemma game and (2) that levels of
      "perverse" punishment of cooperators are not affected by intergroup competition.
      We find confirmation for these hypotheses. However, we find that the effect of
      intergroup competition on the punishment of defectors is fully explained by the
      stronger conditionality of punishment on expected punishment levels in the
      competition condition.

PMID- 22623137
TI  - EUROGIN 2011 roadmap on prevention and treatment of HPV-related disease.
AB  - The EUROGIN 2011 roadmap reviews the current burden of human papillomavirus (HPV)
      related morbidity, as well as the evidence and potential practice recommendations
      regarding primary and secondary prevention and treatment of cancers and other
      disease associated with HPV infection. HPV infection causes ~600,000 cases of
      cancer of the cervix, vulva, vagina, anus and oropharynx annually, as well as
      benign diseases such as genital warts and recurrent respiratory papillomatosis.
      Whereas the incidence of cervical cancer has been decreasing over recent decades,
      the incidence of anal and oropharyngeal carcinoma, for which there are no
      effective screening programs, has been rising over the last couple of decades.
      Randomized trials have demonstrated improved efficacy of HPV-based compared to
      cytology-based cervical cancer screening. Defining the best algorithms to triage
      HPV-positive women, age ranges and screening intervals are priorities for pooled
      analyses and further research, whereas feasibility questions can be addressed
      through screening programs. HPV vaccination will reduce the burden of cervical
      precancer and probably also of invasive cervical and other HPV-related disease in
      women. Recent trials demonstrated that prophylactic vaccination also protects
      against anogenital HPV infection, anogenital intraepithelial lesions and warts
      associated with vaccine types, in males; and anal HPV infection and anal
      intraepithelial neoplasia in MSM. HPV-related oropharyngeal cancer could be
      treated less aggressively because of better survival compared to cancers of the
      oropharynx unrelated to HPV. Key findings in the field of cervical cancer
      prevention should now be translated in cost-effective strategies, following an
      organized approach integrating primary and secondary prevention, according to
      scientific evidence but adapted to the local situation with particular attention
      to regions with the highest burden of disease.

PMID- 22623139
TI  - The recognition signal hypothesis for the adaptive evolution of religion : a
      phylogenetic test with Christian denominations.
AB  - Recent research on the evolution of religion has focused on whether religion is
      an unselected by-product of evolutionary processes or if it is instead an
      adaptation by natural selection. Adaptive hypotheses for religion include direct
      fitness benefits from improved health and indirect fitness benefits mediated by
      costly signals and/or cultural group selection. Herein, I propose that religious
      denominations achieve indirect fitness gains for members through the use of
      ecologically arbitrary beliefs, rituals, and moral rules that function as
      recognition markers of cultural inheritance analogous to kin and species
      recognition of genetic inheritance in biology. This recognition signal hypotheses
      could act in concert with either costly signaling or cultural group selection to
      produce evolutionarily altruistic behaviors within denominations. Using a
      cultural phylogenetic analysis, I show that a large set of religious behaviors
      among extant Christian denominations supports the prediction of the recognition
      signal hypothesis that characters change more frequently near historical schisms.
      By incorporating demographic data into the model, I show that more-distinctive
      denominations, as measured through dissimilar characteristics, appear to be
      protected from intrusion by nonmembers in mixed-denomination households, and that
      they may be experiencing greater biological growth of their populations even in
      the present day.

PMID- 22623140
TI  - An evolutionary account of status, power, and career in modern societies.
AB  - We hypothesize that in modern societies the striving for high positions in the
      hierarchy of organizations is equivalent to the striving for status and power in
      historical and traditional societies. Analyzing a sample of 4,491 US men and
      5,326 US women, we find that holding a supervisory position or being in charge of
      hiring and firing is positively associated with offspring count in men but not in
      women. The positive effect in men is attributable mainly to the higher proportion
      of childlessness among men in non-supervisory positions and those without the
      power to hire and fire. This effect is in accordance with the positive
      relationship between other status indicators and reproductive success found in
      men from traditional, historical, and modern societies. In women, we further find
      a curvilinear relationship between income percentile and offspring number by
      analyzing US census data, indicating that women may strive for resources
      associated with advancement rather than for status per se.

PMID- 22623141
TI  - Protein cross-talk in CD133+ colon cancer cells indicates activation of the Wnt
      pathway and upregulation of SRp20 that is potentially involved in tumorigenicity.
AB  - The cancer stem cell (CSC) theory represents a breakthrough in cancer research.
      We characterized the protein pattern of CSCs to identify specific intracellular
      pathways in this subpopulation of tumor cells. We studied colon CSCs using two
      different colon cancer cell lines: CaCo-2 and HCT-116. Putative CSCs were
      separated from non-CSCs by flow cytometry using CD133 as stemness marker. Total
      protein extracts of CD133+ cells were then compared to protein extracts of CD133-
      cells by 2D DIGE. The protein spots differentially expressed in the two
      subpopulations of cells were analyzed by mass spectrometry. Bioinformatics
      analysis of the identified proteins indicated alteration of two main processes:
      energy metabolism and the Wnt pathway. Interestingly, we observed upregulation of
      the splicing factor SRp20, a newly identified target gene of the Wnt/beta-catenin
      pathway, and we demonstrated a direct cause-effect relationship between Wnt
      pathway activation and the increased SRp20 expression. Our results also show that
      SRp20 influences cell proliferation, which suggests it plays a role in the
      tumorigenicity of CD133+ cells. In conclusion, activation of the Wnt pathway in
      CD133+ cells and upregulation of SRp20, which is implicated in tumorigenesis,
      raises the possibility of a sequential series of molecular events occurring in
      connection with this process.

PMID- 22623142
TI  - Association between type 2 diabetes and rs10811661 polymorphism upstream of
      CDKN2A/B: a meta-analysis.
AB  - To assess the association between type 2 diabetes and rs10811661 polymorphism,
      upstream of CDKN2A/B, a literature-based search was conducted to collect data.
      The pooled OR (odds ratio) and 95 % confidence intervals (CI) were used to assess
      the strength of association between rs10811661 polymorphism and type 2 diabetes.
      OR with 95 % CI were performed for allele contrasts, additive genetic model,
      dominant genetic model and recessive genetic model, respectively. The effect
      model was used if there was heterogeneity between studies. Funnel plots were used
      to predict publication bias. 17 studies with 29,990 cases and 40,977 controls
      were enrolled in this meta-analysis. Significant association was found in all of
      the four genetic models: allele contrast (OR = 1.21, 95 % CI 1.18-1.24), additive
      genetic model (OR = 1.51, 95 % CI 1.40-1.63), dominant genetic model (OR = 1.37,
      95 % CI 1.28-1.47) and recessive genetic model (OR = 1.25, 95 % CI 1.21-1.29).
      The meta-analysis indicated that rs10811661 polymorphism was significantly
      associated with the risk of type 2 diabetes. 

PMID- 22623143
TI  - Elevated white blood cell count is associated with prevalence and development of
      the metabolic syndrome and its components in the general population.
AB  - The metabolic syndrome (MS) is characterized by chronic inflammation. We aimed to
      determine the association of white blood cell (WBC) count with prevalence and
      development of the MS and its components in the general population. A cohort of
      1,329 subjects from the local working population aged 41.3 +/- 7.5 years and
      recruited since 2000-2008 was followed up for 4.0 +/- 1.2 years. WBC count and MS
      components were determined at baseline and follow-up. To determine whether WBC
      predicted incident MS, we used a logistic regression analysis adjusted for
      demographics, baseline variables that define MS components, smoke, medications,
      and follow-up duration. Cross-sectionally in the whole population, WBC count
      increased in parallel with the number of MS components in the same individual,
      and the presence of each component was associated with higher WBC count. Baseline
      WBC count was significantly higher in subjects with prevalent MS. Among subjects
      without MS at baseline, those who developed MS had significantly higher WBC than
      those who did not develop MS at follow-up. Development of each MS component was
      associated with increased WBC count. WBC count remained significantly associated
      with MS development after correction for several potential confounders (OR for 1
      SD increase in WBC 1.26; 95 % CI 1.01-1.58). In conclusion, elevated WBC is
      intimately linked to the prevalence and future development of the MS in a young
      population of working subjects.

PMID- 22623144
TI  - Endovascular treatment of an aortoiliac tuberculous pseudoaneurysm.
AB  - We report a rare case of a tuberculous mycotic aortoiliac pseudoaneurysm treated
      with an endovascular procedure and follow-up of 36 months. The patient was a
      white 72-year-old man with pulmonary tuberculosis and a former smoker with
      hypertension, chronic renal failure, and dyslipidemia. A computed tomographic
      scan of the abdomen and pelvis revealed a left paravertebral cavity with fluid
      content and involvement of vertebrae L2-L4. After a surgical repair attempt, the
      patient was treated with the implant of a bifurcated endoprosthesis. Because it
      is unlikely that any center has extensive experience in the management of this
      rare manifestation of the disease, we reviewed the literature for similar cases.

PMID- 22623145
TI  - Bidirectional association between physical activity and symptoms of anxiety and
      depression: the Whitehall II study.
AB  - Although it has been hypothesized that the association of physical activity with
      depressive and anxiety symptoms is bidirectional, few studies have examined this
      issue in a prospective setting. We studied this bidirectional association using
      data on physical activity and symptoms of anxiety and depression at three points
      in time over 8 years. A total of 9,309 participants of the British Whitehall II
      prospective cohort study provided data on physical activity, anxiety and
      depression symptoms and 10 covariates at baseline in 1985. We analysed the
      associations of physical activity with anxiety and/or depression symptoms using
      multinomial logistic regression (with anxiety and depression symptoms as
      dependent variables) and binary logistic regression (with physical activity as
      the dependent variable). There was a cross-sectional inverse association between
      physical activity and anxiety and/or depressive symptoms at baseline (ORs between
      0.63 and 0.72). In cumulative analyses, regular physical activity across all
      three data waves, but not irregular physical activity, was associated with
      reduced likelihood of depressive symptoms at follow-up (OR = 0.71, 95 % CI 0.54,
      0.99). In a converse analysis, participants with anxiety and depression symptoms
      at baseline had higher odds of not meeting the recommended levels of physical
      activity at follow-up (OR = 1.79, 95 % CI 1.17, 2.74). This was also the case in
      individuals with anxiety and/or depression symptoms at both baseline and follow
      up (OR = 1.70, 95 % CI 1.10, 2.63). The association between physical activity and
      symptoms of anxiety and/or depression appears to be bidirectional.

PMID- 22623146
TI  - Quantitative analysis of binding sites for 9-fluoropropyl-(+)
      dihydrotetrabenazine ([18F]AV-133) in a MPTP-lesioned PD mouse model.
AB  - [18F]AV-133 is a novel PET tracer for targeting the vesicular monoamine
      transporter 2 (VMAT2). The aim of this study is to characterize and quantify the
      loss of monoamine neurons with [18F]AV-133 in the MPTP-lesioned PD mouse model
      using animal PET imaging and ex vivo quantitative autoradiography (QARG).
      METHODS: Optimal imaging time window of [18F]AV-133 was first determined in
      normal C57BL/6 mice (n = 3) with a 90-min dynamic scan. The reproducibility of
      [18F]AV-133 PET imaging was evaluated by performing a test-retest study within 1
      week for the normal group (n = 6). For MPTP-lesioned studies, normal, and MPTP
      treated [25 mg mg/kg once (Group A) and twice (Group B), respectively, daily for
      5 days, i.p., groups of four normal and MPTP-treated] mice were used. PET imaging
      studies at baseline and at Day 4 post-MPTP injections were performed at the
      optimal time window after injection of 11.1 MBq [18F]AV-133. Specific uptake
      ratio (SUr) of [18F]AV-133 was calculated by [(target uptake-cerebellar
      uptake)/cerebellar uptake] with cerebellum as the reference region. Ex vitro QARG
      and immunohistochemistry (IHC) studies with tyrosine hydroxylase antibody were
      carried out to confirm the abundance of dopaminergic neurons. RESULTS: The
      variability between [18F]AV-133 test-retest striatal SUr was 6.60 +/- 3.61% with
      less than 5% standard deviation between animals (intervariability). The
      percentages of MPTP lesions were Group A 0.94 +/- 0.29, -42.1% and Group B 0.65
      +/- 0.09, -60.4%. By QARG, specific binding of [18F]AV-133 was reduced relative
      to the control groups by 50.6% and 60.7% in striatum and by 30.6% and 46.4% in
      substantia nigra (Groups A and B, respectively). Relatively small [18F]AV-133 SUr
      decline was noted in the serotonin and norepinephrine-enriched regions (7.9% and
      9.4% in mid-brain). Results obtained from IHC consistently confirmed the
      sensitivity and selectivity of dopaminergic neuron loss after MPTP treatment.
      CONCLUSIONS: [18F]AV-133 PET SUr displayed a high test-retest stability. The SUr
      significantly declined in the caudate putamen but not in the hypothalamus and
      midbrain regions after MPTP treatment in the mouse brain. The results obtained
      for QARG and IHC were consistent and correlated well with the PET imaging
      studies. On the basis of these concordant results, we find that [18F]AV-133
      should serve as a useful and reliable PET tracer for evaluating nigrostriatal
      degeneration.

PMID- 22623147
TI  - Effectiveness and safety of tranexamic acid in reducing blood loss in total knee
      arthroplasty: a meta-analysis.
AB  - BACKGROUND: Total knee arthroplasty is associated with substantial blood loss and
      the risks of transfusion. Conflicting reports have been published regarding the
      effectiveness and safety of tranexamic acid in reducing postoperative blood loss
      in total knee arthroplasty. We performed a meta-analysis to investigate the
      effectiveness and safety of tranexamic acid in reducing postoperative blood loss
      in total knee arthroplasty. METHODS: A meta-analysis was performed to assess the
      effectiveness and safety of using tranexamic acid in total knee arthroplasty.
      Randomized controlled trials that had been published before May 2011 were
      retrieved, and fifteen studies met the inclusion criteria. The weighted mean
      difference in blood loss, number of transfusions per patient, prothrombin time,
      and postoperative activated partial thromboplastin time and the summary odds
      ratio of transfusion, deep-vein thrombosis, and pulmonary embolism were
      calculated in the group of patients who received tranexamic acid and the group of
      patients who received a placebo. RESULTS: The amount of blood loss and the number
      of blood transfusions per patient were significantly less and the proportion of
      patients who required a blood transfusion was smaller in the tranexamic acid
      group compared with the placebo group. No significant difference in prothrombin
      time, activated partial thromboplastin time, deep-vein thrombosis, and pulmonary
      embolism was detected between the tranexamic acid group and the placebo group.
      CONCLUSIONS: The meta-analysis shows that the use of tranexamic acid for patients
      undergoing total knee arthroplasty is effective and safe for the reduction of
      blood loss.

PMID- 22623148
TI  - Roles of interferon-gamma and its target genes in schizophrenia: Proteomics-based
      reverse genetics from mouse to human.
AB  - A decreased production of interferon gamma (IFNG) has been observed in acute
      schizophrenia. In order to explore the possible relationship between IFNG and
      schizophrenia, we attempted to analyze the differentially expressed proteins in
      the brains of interferon-gamma knockout (Ifng-KO) mice. Five upregulated and five
      downregulated proteins were identified with 2D gels and MALDI-TOF/TOF MS analyses
      in Ifng-KO mouse brain. Of the identified proteins, we focused on creatine kinase
      brain (CKB) and triose phosphate isomerase 1 (TPI1). Consistent with the
      proteomic data, reverse transcriptase-mediated PCR, immunoblotting, and
      immunohistochemistry analyses confirmed that the levels of gene expressions of
      Ckb and Tpi1 were downregulated and upregulated, respectively. When we analyzed
      the genetic polymorphisms of the single nucleotide polymorphisms (SNPs) of their
      human orthologous genes in a Korean population, the promoter SNPs of CKB and TPI1
      were weakly associated with schizophrenia. In addition, IFNG polymorphisms were
      associated with schizophrenia. These results suggest that IFNG and proteins
      affected by IFNG may play a role in the pathogenesis of schizophrenia.

PMID- 22623149
TI  - Neuropathic pain: is quantitative sensory testing helpful?
AB  - Neuropathic pain arises as a consequence of a lesion or disease affecting the
      somatosensory system and is characterised by a combination of positive and
      negative sensory symptoms. Quantitative sensory testing (QST) examines the
      sensory perception after application of different mechanical and thermal stimuli
      of controlled intensity and the function of both large (A-beta) and small (A
      delta and C) nerve fibres, including the corresponding central pathways. QST can
      be used to determine detection, pain thresholds and stimulus-response curves and
      can thus detect both negative and positive sensory signs, the second ones not
      being assessed by other methods. Similarly to all other psychophysical tests QST
      requires standardised examination, instructions and data evaluation to receive
      valid and reliable results. Since normative data are available, QST can
      contribute also to the individual diagnosis of neuropathy, especially in the case
      of isolated small-fibre neuropathy, in contrast to the conventional
      electrophysiology which assesses only large myelinated fibres. For example,
      detection of early stages of subclinical neuropathy in symptomatic or
      asymptomatic patients with diabetes mellitus can be helpful to optimise treatment
      and identify diabetic foot at risk of ulceration. QST assessed the individual's
      sensory profile and thus can be valuable to evaluate the underlying pain
      mechanisms which occur in different frequencies even in the same neuropathic pain
      syndromes. Furthermore, assessing the exact sensory phenotype by QST might be
      useful in the future to identify responders to certain treatments in accordance
      to the underlying pain mechanisms.

PMID- 22623150
TI  - Management of painful diabetic neuropathy: guideline guidance or jungle?
AB  - The treatment of painful diabetic polyneuropathy (PDPN) remains a major
      challenge. A number of reasons have made the guidelines on PDPN management of
      particular interest, including its high prevalence, health and socioeconomic
      impact, interdisciplinary nature and the need for updated evidence-based
      information to refine patient-tailored treatment by weighing up the risks of each
      treatment against its proven benefits, as well as optimizing the use of all
      available resources. The various guidelines on the management of neuropathic pain
      developed so far contain some differences in their work methodology and results.
      Some variations in the recommendations are to be expected but could be
      disorienting and confusing for stakeholders. In this review, a critical
      evaluation of the more recent guidelines on the management of PDPN is provided
      together with highlights on points of agreement and disagreement as well as
      insights into their clinical aspects.

PMID- 22623152
TI  - Multifunctional queen pheromone and maintenance of reproductive harmony in
      termite colonies.
AB  - Pheromones are likely involved in all social activities of social insects
      including foraging, sexual behavior, defense, nestmate recognition, and caste
      regulation. Regulation of the number of fertile queens requires communication
      between reproductive and non-reproductive individuals. Queen-produced pheromones
      have long been believed to be the main factor inhibiting the differentiation of
      new reproductive individuals. However, since the discovery more than 50 years ago
      of the queen honeybee substance that inhibits the queen-rearing behavior of
      workers, little progress has been made in the chemical identification of
      inhibitory queen pheromones in other social insects. The recent identification of
      a termite queen pheromone and subsequent studies have elucidated the multifaceted
      roles of volatile pheromones, including functions such as a fertility signal,
      worker attractant, queen-queen communication signal, and antimicrobial agent. The
      proximate origin and evolutionary parsimony of the termite queen pheromone also
      are discussed.

PMID- 22623151
TI  - Mycorrhiza-induced resistance and priming of plant defenses.
AB  - Symbioses between plants and beneficial soil microorganisms like arbuscular
      mycorrhizal fungi (AMF) are known to promote plant growth and help plants to cope
      with biotic and abiotic stresses. Profound physiological changes take place in
      the host plant upon root colonization by AMF affecting the interactions with a
      wide range of organisms below- and above-ground. Protective effects of the
      symbiosis against pathogens, pests, and parasitic plants have been described for
      many plant species, including agriculturally important crop varieties. Besides
      mechanisms such as improved plant nutrition and competition, experimental
      evidence supports a major role of plant defenses in the observed protection.
      During mycorrhiza establishment, modulation of plant defense responses occurs
      thus achieving a functional symbiosis. As a consequence of this modulation, a
      mild, but effective activation of the plant immune responses seems to occur, not
      only locally but also systemically. This activation leads to a primed state of
      the plant that allows a more efficient activation of defense mechanisms in
      response to attack by potential enemies. Here, we give an overview of the impact
      on interactions between mycorrhizal plants and pathogens, herbivores, and
      parasitic plants, and we summarize the current knowledge of the underlying
      mechanisms. We focus on the priming of jasmonate-regulated plant defense
      mechanisms that play a central role in the induction of resistance by arbuscular
      mycorrhizas.

PMID- 22623153
TI  - Diverse monoclonal antibodies against the CA 19-9 antigen show variation in
      binding specificity with consequences for clinical interpretation.
AB  - The CA 19-9 antigen is currently the best individual marker for the detection of
      pancreatic cancer. In order to optimize the CA 19-9 assay and to develop
      approaches to further improve cancer detection, it is important to understand the
      specificity differences between CA 19-9 antibodies and the consequential affect
      on biomarker performance. Antibody arrays enabled multiplexed comparisons between
      five different CA 19-9 antibodies used in the analysis of plasma samples from
      pancreatic cancer patients and controls. Major differences were observed between
      antibodies in their detection of particular patient samples. Glycan array
      analysis revealed that certain antibodies were highly specific for the canonical
      CA 19-9 epitope, sialyl-Lewis A, while others bound sialyl-Lewis A in addition to
      a related structure called sialyl-Lewis C and modification with Nue5Gc. In a much
      larger patient cohort, we confirmed the binding of sialyl-Lewis C glycan by one
      of the antibodies and showed that the broader specificity led to the detection of
      an increased number of cancer patients without increasing detection of
      pancreatitis patient samples. This work demonstrates that variation between
      antibody specificity for cancer-associated glycans can have significant
      implications for biomarker performance and highlights the value of characterizing
      and detecting the range of glycan structures that are elevated in cancer.

PMID- 22623154
TI  - Nucleoplasmic/nucleolar translocation and identification of a nuclear
      localization signal (NLS) in Dictyostelium BAF60a/SMARCD1 homologue Snf12.
AB  - Dictyostelium is a model eukaryote for the study of several cellular processes;
      however, comparatively little is known about its nucleolus. Identification of
      nucleolar proteins is key to understanding this nuclear subcompartment, but only
      four have been identified in Dictyostelium. As discussed in this article, a
      potential relationship between nucleolar NumA1 and BAF60a/SMARCD1 suggested
      BAF60a may also reside in the nucleolus. Here, we identify BAF60a homologue Snf12
      as the fifth nucleolar protein in Dictyostelium. Immunolocalization experiments
      demonstrate that Snf12 is nucleoplasmic, but translocates to nucleoli upon
      actinomycin-D-induced transcription inhibition (0.05 mg/mL, 4 h). Translocation
      was accompanied by a microtubule-independent protrusion of nucleolar Snf12
      regions from the nucleus followed by detection of Snf12 in cytoplasmic circles
      for at least 48 h. Residues (372)KRKR(375) are both necessary and sufficient for
      nucleoplasmic localization of Snf12 and represent a functional nuclear
      localization signal (NLS), similar to recently identified NLSs in other
      Dictyostelium proteins. Since nucleolar and nucleoplasmic proteins redistribute
      during mitosis, we investigated Snf12 dynamics during this time. Dictyostelium
      undergoes closed mitosis, meaning its nuclear envelope remains intact. Despite
      this, during metaphase and anaphase Snf12 redistributed throughout the cytoplasm
      before reaccumulating in the nucleus during telophase, unlike the previously
      reported nucleoplasmic redistribution of nucleolar NumA1. The nuclear exit of
      Snf12 was independent of its putative nuclear export signal and not inhibited by
      exportin inhibition, suggesting that the redistribution of nuclear proteins
      during mitosis in Dictyostelium is mediated by other mechanisms. Snf12 is the
      second Dictyostelium nucleolar protein for which its dynamics during mitosis have
      been investigated.

PMID- 22623156
TI  - Impact of first metatarsophalangeal joint osteoarthritis on health-related
      quality of life.
AB  - OBJECTIVE: To determine whether there are differences in the foot-specific and
      general health-related quality of life (HRQOL) of people with and without first
      metatarsophalangeal (MTP) joint osteoarthritis (OA). METHODS: The foot-specific
      and general HRQOL of 43 participants (mean +/- SD age 50.0 +/- 10.8 years) with
      symptomatic radiographically confirmed first MTP joint OA (case group) was
      compared to an age-, sex-, and body mass index-matched control group. Foot
      specific HRQOL was assessed using the Foot Health Status Questionnaire (FHSQ) and
      general HRQOL was assessed using the Short Form 36 (SF-36) questionnaire. Both
      questionnaires are validated instruments with 0-100-point domains. RESULTS: All
      domains of the FHSQ were significantly lower in the case group (mean +/- SD foot
      pain 55.5 +/- 22.3 versus 93.0 +/- 7.8, foot function 73.8 +/- 20.9 versus 96.9
      +/- 11.5, footwear 39.1 +/- 28.7 versus 76.6 +/- 27.0, and general foot health
      50.2 +/- 27.0 versus 89.7 +/- 16.0). Further, the SF-36 physical functioning
      domain was significantly lower (mean +/- SD 82.8 +/- 14.7 versus 95.2 +/- 6.3) in
      the case group. CONCLUSION: People with first MTP joint OA experience more foot
      pain, have greater difficulty performing functional weight-bearing activities,
      find it more difficult to obtain suitable footwear, and perceive their feet to be
      in a poorer state of health. Additionally, people with symptomatic first MTP
      joint OA have greater difficulty performing a broad range of physical tasks and
      activities.

PMID- 22623155
TI  - MiR-34a inhibits proliferation and migration of breast cancer through down
      regulation of Bcl-2 and SIRT1.
AB  - MicroRNA-34a(miR-34a), a pivotal member of the p53 network, was found to be down
      regulated in multiple types of tumors and further reported as a tumor suppressor
      microRNA. However, the profile and biological effects of miR-34a in breast cancer
      are still unclear. In this study, we aimed to determine the effect of miR-34a on
      the growth of breast cancer and to investigate whether its effect is achieved by
      targeting Bcl-2 and SIRT1. We examined miR-34a levels in breast cancer cell lines
      and breast cancer specimens by qRT-PCR. Proliferation assay, apoptosis assay, and
      morphological monitoring were performed to assess the tumor suppression effect of
      miR-34a in breast cancer cell lines. Western blotting was used to identify the
      targets of miR-34a. We also investigated the anti-tumor effects of the treatment
      combining miR-34a with 5-FU in breast cancer cells. We found that miR-34a
      expression was down-regulated in 5 breast cancer cell lines compared with the
      immortalized normal mammary epithelial cell line 184A1, and was also down
      regulated by almost 50 % in breast cancer samples compared with their
      corresponding adjacent non-malignant breast tissues. Ectopic restoration of miR
      34a in breast cancer cells suppressed cells proliferation, invasion, and induced
      apoptosis. Bcl-2 and SIRT1 as the targets of miR-34a were found to be in reverse
      correlation with ectopic expression of miR-34a. Furthermore, the treatment
      combining miR-34a with 5-FU significantly showed more efficient anti-tumor
      effects than single treatment of miR-34a or 5-FU. Since miR-34a functions as
      tumor suppressor microRNA in breast cancer, modulating miR-34a level in breast
      cancer was suggested to be a new and useful approach of breast cancer therapy.

PMID- 22623157
TI  - Comparability of stage data in cancer registries in six countries: lessons from
      the International Cancer Benchmarking Partnership.
AB  - The International Cancer Benchmarking Partnership is investigating cancer
      survival differences between six high-income nations using population-based
      cancer registry data. Differences in overall survival are often explained by
      differences in the stage at diagnosis and stage-specific survival. Comparing
      stage at diagnosis using cancer registry data is challenging because of different
      regional practices in defining stage, despite the existence of international
      staging classifications such as TNM. This paper describes how stage data may be
      reconciled for international analysis. Population-based cancer registry data were
      collected for 2.4 million adults diagnosed with colorectal, lung, breast (women)
      or ovarian cancer during 1995-2007 in Australia, Canada, Denmark, Norway, Sweden
      and the United Kingdom. The stage data received were coded to a variety of
      international systems, including the TNM classification, Dukes' for colorectal
      cancer, FIGO for ovarian cancer, and to national "localised, regional, distant"
      categorisations. To optimise comparability for analysis, a rigorous and
      repeatable process was defined to produce a final stage variable for each
      patient. An algorithm was also defined to map TNM, Dukes' and FIGO to a
      "localised, regional, distant" categorisation. We recommend how stage data should
      be recorded and processed to optimise comparability in population-based
      international comparisons of stage-specific cancer outcomes. The process we
      describe to produce comparable stage data forms a benchmark for future research.
      The algorithm to convert between TNM and a "localised, regional, distant"
      categorisation should be valuable for international studies, until global
      consensus is achieved to adhere to a single staging system like TNM.

PMID- 22623158
TI  - Characterization and cell behavior of titanium surfaces with PLL/DNA modification
      via a layer-by-layer technique.
AB  - This study describes the fabrication of two types of multilayered films onto
      titanium by layer-by-layer (LBL) self-assembly, using poly-L-lysine (PLL) as the
      cationic polyelectrolyte and deoxyribonucleic acid (DNA) as the anionic
      polyelectrolyte. The assembling process of each component was studied using
      atomic force microscopy (AFM) and quartz crystal balance (QCM). Zeta potential of
      the LBL-coated microparticles was measured by dynamic light scattering. Titanium
      substrates with or without multilayered films were used in osteoblast cell
      culture experiments to study cell proliferation, viability, differentiation, and
      morphology. Results of AFM and QCM indicated the progressive build-up of the
      multilayered coatings. The surface morphology of three types of multilayered
      films showed elevations in the nanoscale range. The data of zeta potential showed
      that the surface terminated with PLL displayed positive charge while the surface
      terminated with DNA displayed negative charge. The proliferation of osteoblasts
      on modified titanium films was found to be greater than that on control (p <
      0.05) after 3 and 7 days culture, respectively. Alamar blue measurement showed
      that the PLL/DNA-modified films have higher cell viability (p < 0.05) than the
      control. Still, the alkaline phosphatase activity assay revealed a better
      differentiated phenotype on three types of multilayered surfaces compared to
      noncoated controls. Collectively our results suggest that PLL/DNA were
      successfully used to surface engineer titanium via LBL technique, and enhanced
      its cell biocompatibility.

PMID- 22623159
TI  - A journey inside the U28 nanocapsule.
AB  - Anionic uranyl-peroxide U(28)  nanocapsules trap cations and other anions inside,
      whose structures cannot be resolved by X-ray diffraction, owing to
      crystallographic disorder. DFT calculations enabled the complete characterization
      of the geometry of these complex systems and also explained the origin of the
      disorder. The stability of the capsules was strongly influenced by the entrapped
      cations. Excellent agreement between experiment and theory was also obtained for
      the electronic character and redox properties.

PMID- 22623160
TI  - Combination of low doses of enzastaurin and lenalidomide has synergistic activity
      in B-non-Hodgkin lymphoma cell lines.
AB  - Less toxic and more active treatments are needed for indolent lymphomas as there
      is no curative treatment, and patients eventually die due to complications
      related to their disease. The purpose of the present study was to assess the
      antitumour activity of the combination of low doses of Enzastaurin and
      Lenalidomide (Revlimid) on B-lymphoma cell lines. The combination of Enzastaurin
      and Lenalidomide, at doses as low as 1 MUM, showed strong synergism against
      indolent lymphomas by reducing cell growth, producing an increase in G0-G1 phase
      followed by significant decrease in S phase, increasing apoptosis, and inhibiting
      PI3K/AKT, PKC and MAPK/ERK pathways. These preclinical findings, together with
      promising results obtained with Lenalidomide for the treatment of non-Hodgkin
      lymphoma, suggest that further evaluation of the combination of Enzastaurin and
      Lenalidomide for the treatment of indolent lymphomas is warranted. These
      compounds, with a favourable toxicity profile, are not classic chemotherapeutic
      agents, causing severe side effects, and could be considered an example of a new
      innovative attempt of an anti-cancer 'soft treatment'.

PMID- 22623161
TI  - Cell surface expression of CD25 antigen (surface IL-2 receptor alpha-chain) is
      not a prognostic marker in chronic lymphocytic leukemia: results of a
      retrospective study of 281 patients.
AB  - Using the database of the Israeli CLL Study Group, we investigated the incidence
      and prognostic significance of CD25 expression on the surface of lymphocytic
      leukemia cells. Strong CD25 expression was found in 46 (16.4 %) of 281 tested
      cases and was correlated with the presence of splenomegaly (p = 0.04), expression
      of CD38 antigen (p = 0.001), and FMC-7 (p = 0.04). Age, gender, Binet stage,
      circulating lymphocyte count, presence of anemia or thrombocytopenia, atypical
      cell morphology, serum beta 2-microglobulin level, and ZAP-70 expression did not
      differ in patients with or without cell surface CD25. There was no correlation
      between CD25 expression and time to first treatment or overall survival. CD25
      expression does not appear to be a prognostic factor in CLL.

PMID- 22623162
TI  - Fasting glucose level reduction induced by imatinib in chronic myeloproliferative
      disease with TEL-PDGFRbeta rearrangement and type 1 diabetes.

PMID- 22623163
TI  - Molecular engineering of an orthopaedic implant: from bench to bedside.
AB  - The use of metallic implants has revolutionised the practice of orthopaedic
      surgery. While the safety and biocompatibility of these devices are excellent, a
      small percentage becomes infected. These infections are due to the formation of a
      biofilm that harbours bacteria encased in a complex extracellular matrix. The
      matrix serves as a barrier to immune surveillance as well as limiting the
      biocidal effects of systemic and local antibiotics. The objective of the review
      is to describe a novel approach to controlling implant infection using an
      antibiotic that is linked to titanium through a self-assembled monolayer of
      siloxy amines. We show that the hybrid-engineered surface is stable,
      biocompatible and resists colonisation by bacterial species most commonly
      associated with implant-related infections. Studies with rodent bone infection
      models suggest that the engineered titanium surface prevents bone infection.
      Results of a very recent investigation utilising a sheep model of infection
      indicate that the titanium-tethered antibiotic controls infection without
      compromising bone formation and remodelling. From all of these perspectives, the
      tethered antibiotic holds promise of providing a novel and practical approach to
      reducing implant-associated infections.

PMID- 22623164
TI  - Concomitant multipotent and unipotent dental pulp progenitors and their
      respective contribution to mineralised tissue formation.
AB  - Upon in vitro induction or in vivo implantation, the stem cells of the dental
      pulp display hallmarks of odontoblastic, osteogenic, adipogenic or neuronal
      cells. However, whether these phenotypes result from genuine multipotent cells or
      from coexistence of distinct progenitors is still an open question. Furthermore,
      determining whether a single cell-derived progenitor is capable of undergoing a
      differentiation cascade leading to tissue repair in situ is important for the
      development of cell therapy strategies. Three clonal pulp precursor cell lines
      (A4, C5, H8), established from embryonic ED18 first molars of mouse transgenic
      for a recombinant plasmid adeno-SV40, were induced to differentiate towards the
      odonto/osteogenic, chondrogenic or adipogenic programme. Expression of phenotypic
      markers of each lineage was evaluated by RT-PCR, histochemistry or
      immunocytochemistry. The clones were implanted into mandibular incisors or
      calvaria of adult mice. The A4 clone was capable of being recruited towards at
      least 3 mesodermal lineages in vitro and of contributing to dentin-like or bone
      formation, in vivo, thus behaving as a multipotent cell. In contrast, the C5 and
      H8 clones displayed a more restricted potential. Flow cytometric analysis
      revealed that isolated monopotent and multipotent clones could be distinguished
      by a differential expression of CD90. Altogether, isolation of these clonal lines
      allowed demonstrating the coexistence of multipotential and restricted-lineage
      progenitors in the mouse pulp. These cells may further permit unravelling
      specificities of the different types of pulp progenitors, hence facilitating the
      development of cell-based therapies of the dental pulp or other cranio-facial
      tissues.

PMID- 22623165
TI  - Neuroticism mediates the effect of P2RX7 on outcomes of mood disorders.
AB  - BACKGROUND: We previously reported an association between P2RX7 variant rs208294,
      diagnosis, and the longitudinal course of mood disorders. Here, we test whether
      the personality trait neuroticism mediates the effect of P2RX7 on the course of
      mood disorders. METHODS: Patients with DSM-IV mood disorder (256 with major
      depressive disorder and 168 with bipolar disorder [BD]) were diagnosed with
      semistructured interviews, genotyped, and followed up for a median of 60 (range 6
      83) months. The primary outcome was the prospectively assessed proportion of time
      spent in any DSM-IV mood episode (time ill). Three types of genetic effect were
      tested in structural equations models: Model 1: genes directly affect outcome
      independent of neuroticism, Model 2: neuroticism mediates the effect of genes on
      outcome, and Model 3: neuroticism and the genetic variant interact in their
      effect on outcome. RESULTS: Neuroticism mediated the P2RX7 genetic effect on
      outcome. The T allele of rs208294 was associated with higher neuroticism, which
      in turn predicted a higher proportion of time spent in mood episodes (the
      bootstrap-based test of indirect effect, P = .02). There was no significant
      interaction between neuroticism and the genotype. CONCLUSION: Neuroticism is
      likely to lie on the causal pathway between the rs208294 T variant and the
      adverse long-term course of major depressive and BDs.

PMID- 22623166
TI  - Atmospheric deposition studies of heavy metals in Arctic by comparative analysis
      of lichens and cryoconite.
AB  - Lichens and cryoconite (rounded or granular, brownish-black debris occurring in
      holes on the glacier surface) from Ny-Alesund were used for understanding the
      elemental deposition pattern in the area. Lichen samples collected from low-lying
      coastal region and cryoconite samples from high altitudinal glacier area were
      processed and analysed for elements such as aluminium (Al), arsenic (As), cadmium
      (Cd), cobalt (Co), chromium (Cr), cesium (Cs), copper (Cu), iron (Fe), manganese
      (Mn), nickel (Ni), lead (Pb), vanadium (V) and zinc (Zn) through inductively
      coupled plasma mass spectrometry. Results showed that heavy metals, Al and Fe,
      are present in high concentration in the cryoconite samples. Al was also present
      in high amounts in seven of the eight lichen samples studied. The general scheme
      of elements in the decreasing order of their concentrations for most of the
      cryoconite samples was Al > Fe > Mn > Zn > V > Pb > Cr > Ni > Cu > Co > As > Cs >
      Cd while that for the lichen samples was Al > Fe > Zn > Mn > Pb > Cu > Cs > Cr >
      Ni > V > Co > As > Cd. Similarity in trends in the two sample types confirms that
      the environment indeed contains these elements in that order of concentration
      which overtime got accumulated in the samples. Overall comparison showed most
      elements to be present in high concentrations in the cryoconite samples as
      compared to the lichen samples. Within the lichens, elemental accumulation data
      suggests that the low-lying site (L-2) from where Cladonia mediterranea sample
      was collected was the most polluted accumulating a number of elements at high
      concentrations. The probable reasons for such deposition patterns in the region
      could be natural (crustal contribution and sea salt spray) and anthropogenic
      (local and long-distance transmission of dust particles). In the future, this
      data can form a baseline for monitoring quantum of atmospheric heavy metal
      deposition in lichens and cryoconite of Svalbard, Arctic.

PMID- 22623167
TI  - Temporal scale-induced uncertainty in load duration curves for instream-dissolved
      oxygen.
AB  - Load duration curves were developed using the Hydrological Simulation Program
      FORTRAN (HSPF) for dissolved oxygen (DO) for the Amite River in Louisiana, USA.
      The concept of 'dissolved oxygen reserve', defined as the total quantity of DO,
      is introduced. The effect of temporal resolution on duration curves of DO reserve
      was examined using duration curves developed based on daily, weekly, biweekly,
      and monthly average data. Duration curves for DO exhibited high variability in
      the load estimated using daily data as compared to those based on biweekly and
      monthly data. A seasonal analysis revealed the trend in the DO reserve. The daily
      DO reserve for the Amite River at Port Vincent was 44,049.31 kg when daily summer
      data were used and 74,255.15 kg for daily annual data. A surplus of 10,691 kg of
      DO reserve was shown in the monthly data during critical summer months. The
      coefficient of variation (CV), used to define the temporal scale-induced
      uncertainty, was found to be linearly and inversely correlated with the logarithm
      of the time scale. Regression equations were developed to extrapolate near real
      time flow and water quality data, greatly simplifying flow and water quality
      monitoring and reducing the cost involved in flow and water quality monitoring.

PMID- 22623168
TI  - Impact of industrial waste effluents on river Damodar adjacent to Durgapur
      industrial complex, West Bengal, India.
AB  - The present study deals with the characterization of industrial effluents
      released from various industries and distribution of heavy metals in effluent
      discharge channel and its impact on the river Damodar. The effluent of tamlanala,
      a natural storm water channel, is extensively used for irrigation for growing
      vegetables in and around the study area. The heavy metals in water of the study
      area are in the order of Fe > Mn > Pb > Cd and sediments follow similar trends
      too. The enrichment of heavy metals in the sediments are in the order of Cd
      (39.904) > Pb (33.156) > Mn (0.164) > Fe (0.013). The geoaccumulation index
      values reveal effluent channel is subjected to moderate to high pollution with
      respect to Cd (4.733) and Pb (4.466). The analyzed data for enrichment factors
      and the pollution load index (1.305) show that effluent channels have suffered
      from significant heavy metal contamination following industrialization and
      urbanization. Compared to baseline values, the surface sediment layers show high
      enrichment across the channel and at its discharge point. The factor analysis
      reveals three factors-industrial sources, surface runoff inputs, and background
      lithogenic factors which clarify the observed variance of the environmental
      variables. Metal pollution assessment of sediments suggests that pollution from
      the heavy metals observed is high in the tamlanala which in turn affects the
      downstream of the river system.

PMID- 22623169
TI  - HIV and aging.

PMID- 22623170
TI  - Intravenous dosing conditions may affect systemic clearance for highly lipophilic
      drugs: implications for lymphatic transport and absolute bioavailability studies.
AB  - The clearance (Cl) and volume of distribution (V(ss)) of a lipophilic,
      lymphatically transported drug, halofantrine (Hf) have been evaluated after
      intravenous delivery to the systemic circulation in ex vivo lymph and plasma, and
      compared with the data obtained after administration of a lipid-based emulsion
      and a lipid-free cosolvent formulation. Systemic Cl and V(ss) were significantly
      lower (approximately twofold) after delivery of Hf in lymph or the emulsion when
      compared with the administration in plasma or the cosolvent formulation.
      Preadministration of drug-free lymph, immediately before administration of drug
      in plasma, however, resulted in plasma profiles consistent with that obtained
      after administration of drug in lymph/emulsion. Where drug and lipid entered the
      systemic circulation coincidentally, systemic Cl of Hf, therefore, appeared to be
      relatively unaffected by the route of entry to the systemic circulation (i.e. via
      the lymph or the blood), but more significantly altered by total plasma lipid
      levels. Because temporal changes to plasma lipid levels occur as a result of the
      absorption of formulation or food-derived lipids and the infusion of intravenous
      lipid emulsions, the current data suggest that a mismatch in plasma lipid levels
      after intravenous and oral administrations may lead to differences in drug Cl and
      errors in bioavailability assessment.

PMID- 22623171
TI  - Proteomic tracking and analysis of a bacterial mixed culture.
AB  - To improve the understanding of microbial behaviors in communities, proteomic
      tracking, an approach for relative quantification of species-specific population
      dynamics of mixed cultures, was developed. Therefore, a bacterial mixed culture
      was analyzed during batch cultivations with and without addition of the
      antibiotic Ceftazidime. The community was composed of Burkholderia cepacia,
      Pseudomonas aeruginosa, and Staphylococcus aureus, pathogens causing infections
      in cystic fibrosis patients. Gel-based proteomics and mass spectrometry were used
      to obtain qualitative and quantitative proteomic data. During cultivation, P.
      aeruginosa became dominant within the mixed culture while S. aureus was inhibited
      in growth. Analysis of samples - taken along cultivation - revealed about 270
      differentially expressed proteins. Some of those proteins are related to
      bacterial interactions, response to antibiotic treatment or metabolic shifts. For
      instance, the enzymes PhzS(flavin-containing monooxygenase), PhzD (phenazine
      biosynthesis protein), and PhzG2 (pyridoxamine 5'-phosphate oxidase) indicated
      the production of the antibiotic pigment pyocyanine by P. aeruginosa that is
      related to oxidative stress and therefore, might inhibit growth of S. aureus.
      Overall, the strategy applied not only allows species-specific tracking of the
      community composition but also provides valuable insights into the behavior of
      mixed cultures.

PMID- 22623173
TI  - Improved osteoblast compatibility of medical-grade polyetheretherketone using arc
      ionplated rutile/anatase titanium dioxide films for spinal implants.
AB  - Titanium dioxide (TiO(2)), known to exhibit good biocompatibility, is applied in
      this study as a thin film formed onto polyetheretherketone (PEEK) substrate,
      which has been widely used in spinal interbody fusion cages. For successful
      deposition, an arc ionplating (AIP) technique was applied to deposit TiO(2) at
      low deposition temperature without damaging PEEK substrate, while providing
      satisfactory film adhesion. This study systematically investigates the effects of
      TiO(2) thin film phase composition and surface characteristics, controlled by
      using different target current and substrate bias, on osteoblast compatibility.
      Experimental results showed that anatase phase (A-TiO(2)) and/or rutile phase (R
      TiO(2) ) TiO(2) coatings, respectively, can be prepared in appropriate deposition
      conditions. Overall, the TiO(2)-coated PEEK presented better osteoblast
      compatibility than the bare PEEK material in terms of cell adhesion, cell
      proliferation, and cell differentiation abilities, as well as osteogenesis
      performance (as determined by levels of osteopontin, osteocalcin, and calcium
      content). Surface roughness and hydrophilicity of the AIP-TiO(2) films were found
      to be responsible for significant osteoblast cell growth. It is also noticeable
      that the R-TiO(2) exhibited better osteoblast compatibility than the A-TiO(2) due
      to the presence of negatively charged hydroxyl groups on R-TiO(2) (110) surface
      in nature.

PMID- 22623172
TI  - Intermittent parathyroid hormone administration converts quiescent lining cells
      to active osteoblasts.
AB  - Intermittent administration of parathyroid hormone (PTH) increases bone mass, at
      least in part, by increasing the number of osteoblasts. One possible source of
      osteoblasts might be conversion of inactive lining cells to osteoblasts, and
      indirect evidence is consistent with this hypothesis. To better understand the
      possible effect of PTH on lining cell activation, a lineage tracing study was
      conducted using an inducible gene system. Dmp1-CreERt2 mice were crossed with
      ROSA26R reporter mice to render targeted mature osteoblasts and their
      descendents, lining cells and osteocytes, detectable by 5-bromo-4-chloro-3
      indolyl-beta-d-galactopyranoside (X-gal) staining. Dmp1-CreERt2(+):ROSA26R mice
      were injected with 0.25 mg 4-OH-tamoxifen (4-OHTam) on postnatal days 3, 5, 7,
      14, and 21. The animals were euthanized on postnatal day 23, 33, or 43 (2, 12, or
      22 days after the last 4-OHTam injection). On day 43, mice were challenged with a
      subcutaneous injection of human PTH (1-34, 80 ug/kg) or vehicle once daily for 3
      days. By 22 days after the last 4-OHTam injection, most X-gal (+) cells on the
      periosteal surfaces of the calvaria and the tibia were flat. Moreover, bone
      formation rate and collagen I(alpha1) mRNA expression were decreased at day 43
      compared to day 23. After 3 days of PTH injections, the thickness of X-gal (+)
      cells increased, as did their expression of osteocalcin and collagen I(alpha1)
      mRNA. Electron microscopy revealed X-gal-associated chromogen particles in thin
      cells prior to PTH administration and in cuboidal cells following PTH
      administration. These data support the hypothesis that intermittent PTH treatment
      can increase osteoblast number by converting lining cells to mature osteoblasts
      in vivo.

PMID- 22623174
TI  - Splenic infarction, warm autoimmune hemolytic anemia and antiphospholipid
      antibodies associated with systemic lupus erythematosus.

PMID- 22623175
TI  - Primary schwannoma of the thyroid gland involving the isthmus: report of a case.
AB  - Primary thyroid schwannomas are extremely rare tumors and there are very few
      reports of such tumors in the literature. This report presents a rare case of
      schwannoma involving the isthmus of the thyroid in a 47-year-old male, presenting
      as a symptomatic predominating cold nodule within a multinodular goiter. The
      patient underwent total thyroidectomy. The histological examination indicated an
      Antoni A-type schwannoma. The clinical, radiological and pathological findings of
      the tumor are discussed, emphasizing the difficulty in reaching a correct
      preoperative diagnosis. Only 18 cases of primary schwannoma of the thyroid gland
      have so far been described in the literature and, this is only the second report
      of thyroid schwannoma localized in the isthmus.

PMID- 22623176
TI  - The ovarian cancer-derived secretory/releasing proteome: A repertoire of tumor
      markers.
AB  - Ovarian cancer is the most lethal gynecological malignancy worldwide, and early
      detection of this disease using serum or plasma biomarkers may improve its
      clinical outcome. In the present study, a large scale protein database derived
      from ovarian cancer was created to enable tumor marker discovery. First, primary
      organ cultures were established with the tumor tissues and corresponding normal
      tissues obtained from six ovarian cancer patients, and the serum-free conditioned
      medium (CM) samples were collected for proteomic analysis. The total proteins
      from the CM sample were separated by SDS-PAGE, digested with trypsin and then
      analyzed by LC-MS/MS. Combining data from the tumor tissues and the normal
      tissues, 1129 proteins were identified in total, of which those categorized as
      "extracellular proteins" and "plasma membrane proteins" accounted for 21.4% and
      16.9%, respectively. For validation, three secretory proteins (NID1, TIMP2, and
      VCAN) involved in "organ development"-associated subnetwork, showed significant
      differences between their levels in the circulating plasma samples from ovarian
      cancer patients and healthy women. In conclusion, this ovarian cancer-derived
      protein database provides a credible repertoire of potential biomarkers in blood
      for this malignant disease, and deserves mining further.

PMID- 22623177
TI  - Vitamin D and pregnancy: skeletal effects, nonskeletal effects, and birth
      outcomes.
AB  - The function and requirement of vitamin D during pregnancy for both mother and
      fetus have remained a mystery. This fact was highlighted by The Cochrane Review
      in 2000, which reported a lack of randomized controlled trials (RCTs) with
      respect to vitamin D requirements during pregnancy. Unfortunately, during the
      past decade only a single RCT has been performed with respect to vitamin D
      requirements during pregnancy. In this review we will discuss vitamin D
      metabolism during pregnancy as well as the consequences of vitamin D deficiency
      on skeletal, nonskeletal, and birth outcomes using birth observational data and
      data from our recent RCT. New RCT data strongly support previous observational
      studies in that improving nutritional vitamin D status will improve birth
      outcomes. The new RCT data indicate that 4,000 IU/day vitamin D(3) during
      pregnancy will "normalize" vitamin D metabolism and improve birth outcomes
      including primary cesarean section and comorbidities of pregnancy with no risk of
      side effects.

PMID- 22623178
TI  - Incidental findings with dual-energy X-ray absorptiometry: spectrum of possible
      diagnoses.
AB  - New dual-energy X-ray absorptiometry (DXA) technologies provide improved spatial
      resolution and high image quality. Our purpose was to review DXA examinations to
      detect collateral findings and to understand their potential impact on patient
      healthcare. We retrospectively and randomly reviewed 739 DXA examinations (191 of
      739, 25.8 %, whole body; 96 of 739, 13.0 %, vertebral fracture assessment; 231 of
      739, 31.3 %, lumbar spine; 221 of 739, 29.9 %, femur) that were performed in our
      institution with a new DXA equipment. Whenever an extra finding was discovered,
      the physician's report was read and the clinical history of the patient was
      investigated to understand whether that finding was already known, as well as to
      check the diagnosis. The population included 208 male and 531 female subjects (58
      +/- 14 years old). Incidental findings were detected in 117 (15.8 %) of 739 DXA
      examinations (17 of 117, 14.5 %, whole body; 41 of 117, 35.0 %, vertebral
      fracture assessment; 32 of 117, 27.4 %, lumbar spine; 27 of 117, 23.1 %, femur):
      biliary and urinary stones (4.8 %), vascular calcifications (33.7 %), other soft
      tissue calcifications (25.3 %-e.g., tendons, lymph nodes, intraparenchymatous
      calcifications), vertebral abnormalities (14.5 %), other bone abnormalities (12.1
      %), and morphovolumetric alterations or abnormal anatomical structures (9.6 %).
      Among all these findings, 50 (42.7 %) of 117 could be verified by other imaging
      modalities. Forty-nine (98.0 %) of 50 incidental findings were identified as true
      findings, and DXA was able to orient the diagnosis (exact diagnosis in 37 of 50,
      74.0 %); however, none of them was mentioned on available DXA reports. An
      interpreting physician should treat the DXA image with the same attention given
      to any other X-ray image. Sometimes DXA may allow a qualitative diagnosis of
      collateral findings. However, potential negative effects on healthcare economy
      should be considered for false-positive or insignificant findings.

PMID- 22623181
TI  - Differential effects of age on human striatal adenosine A1 and A(2A) receptors.
AB  - The aim of this study was to investigate the effect of age on the distribution of
      adenosine A1 receptors (A1Rs) and adenosine A(2A) receptors (A(2A)Rs) in the
      striatum of healthy subjects using PET imaging with 8-dicyclopropylmethyl-1
      [11C]methyl-3-propylxanthine ([11C]MPDX) and [7-methyl-11C]-(E)-8-(3,4,5
      trimethoxystyryl)-1,3,7-trimethylxanthine ([11C]TMSX), respectively. We recruited
      8 young (22.0 +/- 1.7 years) and 10 elderly (65.4 +/- 7.6 years) volunteers to
      undergo [11C]MPDX PET scanning, and 11 young (22.7 +/- 2.7 years) and six elderly
      (60.7 +/- 8.5 years) volunteers to undergo [11C]TMSX PET scanning. A dynamic
      series of decay-corrected PET scans was performed for 60 min following injection
      of [11C]MPDX or [11C]TMSX. We calculated the binding potential (BP(ND) ) of
      [11C]MPDX and distribution volume ratio (DVR) of [11C]TMSX in the striatum. The
      BP(ND) of [11C]MPDX was significantly lower in elderly than in young subjects,
      both in the putamen and head of the caudate nucleus. The BP(ND) was negatively
      correlated with age in both the putamen and the head of the caudate nucleus.
      However, no difference was found between the DVR of [11C]TMSX in the striata of
      young and elderly subjects, nor was there a correlation between age and the DVR
      of [11C]TMSX. The effect of age on the distribution of A1Rs in the human striatum
      described herein is similar to previous reports of age-related decreases in
      dopamine D1 and D2 receptors. Unlike A1Rs, however, this study suggests that the
      distribution of A(2A) Rs does not change with age.

PMID- 22623182
TI  - Pre-diagnostic alcohol consumption and breast cancer recurrence and mortality:
      results from a prospective cohort with a wide range of variation in alcohol
      intake.
AB  - The association between pre-diagnostic alcohol consumption and breast cancer
      recurrence and breast cancer specific mortality was investigated in 1,052 women
      diagnosed with early breast cancer in a prospective cohort of 29,875 women. Known
      clinical, lifestyle and socioeconomic risk factors were evaluated and adjusted
      for in multivariate analysis. We found a modest but significant association
      between pre-diagnostic alcohol consumption and breast cancer recurrence with a
      median follow-up of six years after date of diagnosis, both when using baseline
      measures of alcohol intake (HR, 1.65; 95% CI, 1.02-2.67; >2 units/day vs. <=1
      unit/day) and cumulated alcohol intake (HR, 2.02; 95% CI, 1.06-3.85; >40 drinking
      years vs. 0<drinking years<=10). Results for breast cancer specific mortality
      were also suggestive of a higher risk but were not statistically significant. In
      addition to being a risk factor for breast cancer, a high pre-diagnostic alcohol
      intake also seems to have an effect on the course of the disease. We could not
      relate the finding to a specific tumor presentation.

PMID- 22623180
TI  - Novel treatments for NEC: keeping IBD in mind.
AB  - Necrotizing enterocolitis (NEC) is an inflammatory intestinal disease of
      premature newborns, thought to result in part from overactivity of the innate
      immune system. NEC has been well-studied from the perspective of prevention;
      however, after the disease onset, there are limited treatment options to control
      its progression. This review discusses four potential therapies that target the
      overactive immune response in NEC: pentoxifylline, platelet activating factor
      modulators, glucocorticoids, and vasoactive substances. In addition, given the
      similar pathogenesis of NEC and inflammatory bowel disease (IBD), we propose that
      IBD therapies could provide promising leads for novel strategies with which to
      treat NEC.

PMID- 22623184
TI  - Molecular and structural characterization of the SH3 domain of AHI-1 in
      regulation of cellular resistance of BCR-ABL(+) chronic myeloid leukemia cells to
      tyrosine kinase inhibitors.
AB  - ABL tyrosine kinase inhibitor (TKI) therapy induces clinical remission in chronic
      myeloid leukemia (CML) patients but early relapses and later emergence of TKI
      resistant disease remain problematic. We recently demonstrated that the AHI-1
      oncogene physically interacts with BCR-ABL and JAK2 and mediates cellular
      resistance to TKI in CML stem/progenitor cells. We now show that deletion of the
      SH3 domain of AHI-1 significantly enhances apoptotic response of BCR-ABL(+) cells
      to TKIs compared to cells expressing full-length AHI-1. We have also discovered a
      novel interaction between AHI-1 and Dynamin-2, a GTPase, through the AHI-1 SH3
      domain. The crystal structure of the AHI-1 SH3 domain at 1.53-A resolution
      reveals that it adopts canonical SH3 folding, with the exception of an unusual C
      terminal alpha helix. PD1R peptide, known to interact with the PI3K SH3 domain,
      was used to model the binding pattern between the AHI-1 SH3 domain and its
      ligands. These studies showed that an "Arg-Arg-Trp" stack may form within the
      binding interface, providing a potential target site for designing specific
      drugs. The crystal structure of the AHI-1 SH3 domain thus provides a valuable
      tool for identification of key interaction sites in regulation of drug resistance
      and for the development of small molecule inhibitors for CML.

PMID- 22623183
TI  - Resources and interest among faith based organizations for influenza vaccination
      programs.
AB  - In the United States, annual influenza vaccination rates are suboptimal and are
      well below the national health objectives. Project VIVA mobilized community
      members and organizations to implement an influenza vaccination program in Harlem
      by administering vaccines in "non-traditional" venues, such as community-based
      organizations, pharmacies, and faith-based organizations (FBOs). FBOs have been
      recognized as important venues for health promotion initiatives within medically
      underserved communities. However, data regarding the extent of resources and
      interest in health promotion programs among FBOs are sparse. We conducted a
      telephone survey among 115 FBOs in three New York City neighborhoods with
      histories of low influenza immunization rates to identify the congregation's
      health concerns, interest in serving as a community-based venue for influenza
      vaccinations, and existing resources for health programming. Twenty-six percent
      of the FBOs had an established health ministry, while 45 % expressed interest in
      developing one. Seven percent included nurses among their health activities and
      16.5 % had contact with the local health department. Most FBOs expressed interest
      in common health promotions programs; 60 % expressed interest in providing on
      site influenza vaccination programs within their organization. Health programs
      within FBOs can be a point of access that may improve the health of their
      congregants as well as the larger community. 

PMID- 22623185
TI  - Chemometric evaluation of physicochemical properties of carbonated-apatitic
      preparations by Fourier transform infrared spectroscopy.
AB  - The purpose of this study was to develop a simple and quick method of evaluating
      the physicochemical properties of carbonated apatite preparations (CAP) as an
      index of the bioaffinity of implantable materials based on Fourier-transformed
      infrared (IR) spectra by chemometrics. The wet-synthesized CAPs contained various
      levels of carbonate content (CO(3)), and were analyzed microstrain parameter
      (MS), crystallite size parameter (CP), specific surface area (Sw), CO(3), and
      solubility parameter (pK(HAP)) using by X-ray powder diffraction, nitrogen gas
      adsorption, IR, and UV absorption. The IR spectral results of CAPs suggested that
      the peak intensities of CAP reflected the physicochemical properties of the
      samples. The IR data sets were calculated to obtain calibration models evaluating
      the physicochemical properties of CAPs by a partial least squares regression
      analysis (PLS). As validation of the calibration model, physicochemical
      properties of CAP could be evaluated based on validation IR data sets of
      independent samples, and those values had sufficient accuracy. The regression
      vector of each calibration model suggested that the physicochemical properties of
      CAP, such as CO(3), Sw, MS, CP, and pK(HAP), were affected by phosphate,
      hydroxyl, and carbonate groups.